PMID- 8732687
TI  - G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and
      calcitonin receptors to phospholipase C in COS-7 cells.
AB  - The PTH/PTH-related peptide (PTHrP) receptor and the calcitonin receptor mediate
      the action of their physiological ligands by activating two different effectors,
      adenylyl cyclase and phospholipase C. Whereas regulation of adenylyl cyclase via
      both receptors is thought to involve the G protein G(s), it is not known whether
      activation of phospholipase C results from coupling of the receptors to G(q)
      family members or whether beta gamma-subunit released from receptor-activated
      G(s) lead to phospholipase C activation. To elucidate the mechanism of this type
      of dual signaling, we reconstituted the signal transduction of the PTH/PTHrP and
      the calcitonin receptor in COS-7 and HEK293 cells. In COS-7 cells expressing the
      receptor alone, addition of the respective ligands resulted in the accumulation
      of cAMP and inositol phosphates. When cells were cotransfected with the cDNAs of
      receptor and different alpha-subunits of the Gq family (G alpha q, G alpha 11, G
      alpha 14, G alpha 15, and G alpha 16, a severalfold increase in the ligand
      dependent inositol phosphate production could be observed, indicating that the
      receptors functionally interacted with all alpha-subunits of the G alpha q
      family. Additionally, whereas PTH treatment of HEK293 cells coexpressing both the
      PTH/PTHrP receptor and G alpha q increased both second messengers, the same
      treatment in cells expressing the PTH/PTHrP receptor alone increased only cAMP.
      Under all conditions tested, activation of phospholipase C via the PTH/PTHrP and
      calcitonin receptor required higher ligand concentrations than receptor-mediated
      adenylyl cyclase activation. Our data strongly support the idea that dual
      signaling of the PTH/PTHrP and calcitonin receptors is due to the a activation of
      different G proteins belonging to the G(s) and G(q) families.

PMID- 8732688
TI  - Modulation of insulin signal transduction by eutopic overexpression of the
      receptor-type protein-tyrosine phosphatase LAR.
AB  - Protein-tyrosine phosphatases (PTPases) regulate insulin signaling by catalyzing
      the tyrosine dephosphorylation of the insulin receptor and its substrate
      proteins. Previous studies have implicated a PTPase localized to a cell membrane
      fraction in the regulation of the insulin receptor in situ. LAR (leukoyte antigen
      related) is a transmembrane PTPase in insulin-sensitive tissues with in vitro
      catalytic specificity for the insulin receptor kinase domain. When transfected
      into Chinese hamster ovary cells overexpressing the human insulin receptor (CHO
      hlR), the LAR protein was processed as expected into an 85-kDa subunit containing
      the transmembrane and cytoplasmic domains. LAR was increased an average of 6-fold
      in clonal lines of stably transfected cells, and cell fractionation confirmed its
      localization in the cell membrane. After stimulation with 100 nM insulin,
      tyrosine phosphorylation of the insulin receptor was decreased by 31% at 1 min (P
      < 0.01) and by 42% at 10 min (P < 0.01), and that of IRS-1 was decreased by 34%
      (P < 0.01) at 1 min and by 56% (P < 0.01) at 10 min in the LAR-overexpressing
      cells compared with empty vector transfectants. LAR overexpression also blocked
      insulin-stimulated receptor kinase activation as well as thymidine incorporation
      into DNA. Quantitatively similar results were obtained in populations of CHO-hlR
      cells transfected transiently by electroporation. In contrast, overexpression of
      recombinant LAR cytoplasmic domain, detected as a 72-kDa protein in the cell
      cytosol, did not significantly affect the insulin-stimulated tyrosine
      phosphorylation of the insulin receptor or IRS-1 (99% and 93% of control at 10
      min, respectively). These studies provide the first evidence that increased
      expression of LAR has negative regulatory effects at a proximal site in the
      insulin-signaling pathway. Since this effect occurs only when LAR is eutopically
      expressed at the cell membrane, these data further suggest that LAR requires a
      transmembrane localization to directly interact with the insulin receptor in
      situ.

PMID- 8732689
TI  - Variegated expression of a mouse steroid 21-hydroxylase/beta- galactosidase
      transgene suggests centripetal migration of adrenocortical cells.
AB  - 5'-Flanking sequences (6.4 kb) of the mouse steroid 21-hyrodxylase (21-OHase) A
      gene linked to a LacZ reporter gene directed appropriate cell-specific expression
      in cultured Y1 adrenocortical tumor cells and in the adrenal cortex of transgenic
      mice. The transgene expression initiated at the same stage of adrenal development
      as the endogenous 21-OHase gene (embryonic day 11.5). Although the endogenous 21
      OHase gene is expressed throughout the adrenal cortex, the 21-OHase/beta-gal
      transgene showed a strikingly variegated pattern of adrenocortical expression in
      all 10 transgene-expressing mouse lines examined. This presents as radial stripes
      of beta-gal staining transcending the classical zonal structure of the adrenal
      cortex but paralleling the columnar arrangement of cells of the zona fasciculata
      on the centripetal organization of the adrenocortical blood supply. To the extent
      that the variegated pattern of 21-OHase/beta-gal transgene expression depicts
      adrenocortical cell lineage, these results suggest that all cells within an
      individual stripe have a common clonal origin; the radial pattern of clonally
      derived cells argues that cellular migration maintains the adult adrenocortical
      cell population. Adrenal glands of developing embryos also exhibited a variegated
      pattern of 21-OHase/beta-gal transgene expression. However, this presented as
      islands of beta-gal reporter staining within the developing gland, suggesting
      that the rapid embryonic adrenal growth phase, which precedes the establishment
      of the classic adrenocortical zonal structure, may be governed by cellular
      mechanisms distinct from those responsible for maintenance of the adult
      adrenocortical cell population.

PMID- 8732690
TI  - Dynamic monitoring and quantification of gene expression in single, living cells:
      a molecular basis for secretory cell heterogeneity.
AB  - Progress in understanding the dynamics of gene expression has been hampered by
      lack of a strategy for continuously monitoring this process within normal, living
      cells. Here, we employed a modification of conventional luciferase technology to
      make single and repeated real-time measurements of PRL gene expression from
      individual, living lactotropes from nursing rats. Cells were individually
      transfected by microinjection with a PRL promoter/luciferase reporter construct.
      Levels of PRL gene transcription were quantified by photonic imaging in the same
      cells before and after 24 h of culture in the presence or absence of the dopamine
      agonist bromocryptine or epidermal growth factor, two well known regulators of
      PRL gene transcription. We found these cells to be remarkably heterogeneous with
      respect to basal PRL gene expression and that the degree of activity within a
      single cell could fluctuate greatly over time under basal culture conditions.
      Treatment with bromocryptine or epidermal growth factor induced predictable and
      reversible changes in the average responses observed, yet individual cells
      displayed marked differences in response to these agents. These findings
      demonstrate the utility of this paradigm for monitoring dynamics of gene
      expression within normal, living cells of any type. Moreover, they provide a
      molecular basis for the secretory heterogeneity and plasticity that have come to
      be known as hallmarks of lactotrope cell function.

PMID- 8732691
TI  - A new reagent for the induction of T-cell depletion, anti-CD3-CRM9.
AB  - We have developed a new reagent for inducing in vivo T-cell depletion and have
      tested this reagent in rhesus monkeys. The reagent is an anti-CD3 epsilon
      immunotoxin based on a diphtheria toxin binding-site mutant, CRM9. After
      administration to monkeys, T cells are depleted from both the blood and lymph
      node compartments to < 1% of their initial values. T-cell depletion is associated
      with transient immunosuppression, as judged by delayed rejection of RhLA
      mismatched skin allografts. T cells are repopulated in both compartments;
      however, the rate of repopulation is age dependent. The rate is rapid in juvenile
      animals (12 days) and requires > 30 days in old animals. The correlation between
      repopulation rate and age suggests that the repopulation is thymus dependent and
      that the repopulated T cells are probably naive T cells. This reagent should be a
      valuable tool in studying the role of memory T cells in rhesus models of
      autoimmune diseases and protocols of tolerance induction after organ
      transplantation.

PMID- 8732692
TI  - Differential in vitro and in vivo antitumor effects mediated by anti-CD40 and
      anti-CD20 monoclonal antibodies against human B-cell lymphomas.
AB  - The antitumor effects of CD40 and CD20 monoclonal antibodies (mAbs) were compared
      on various human B-cell lymphomas by using both in vitro and in vivo assays. Anti
      CD40 directly inhibited the proliferation of human B-cell lymphomas in vitro,
      whereas anti-CD20 exerted no inhibitory effects on the growth of any lymphoma
      tested. These lymphomas were then injected into immunodeficient mice to examine
      the antitumor efficacy of these unconjugated mAbs in vivo. This xenogeneic model
      was used in the evaluation of various potential therapeutic agents against human
      cancers in an in vivo setting. Surprisingly, in contrast to its negligible
      effects on lymphoma growth in vitro, anti-CD20 was more efficacious than anti
      CD40 in promoting the survival of mice bearing some but not all lymphoma lines.
      To determine whether the antitumor effects of these mAbs were direct or indirect
      in vivo, we concurrently treated tumor-bearing mice with mAbs to the murine Fc
      receptor to block antibody-dependent cell-mediated cytotoxicity (ADCC). When
      these neutralizing antibodies against Fc receptors were administered at the same
      time as mAb treatment, the antitumor effects of anti-CD20 in vivo were completely
      abrogated, whereas anti-CD40 treatment, although also diminished, still provided
      significant antitumor effects. These results indicate that the in vivo antitumor
      activity of the murine anti-human CD20 mAb was primarily due to ADCC by murine
      effector cells, which may not translate into comparable effects in humans. By
      contrast, anti-CD40 may be of potential clinical use in the treatment of
      lymphomas in humans because of its additional direct anti-proliferative effects.
      The results also demonstrate a possible difficulty in accurately evaluating the
      potential clinical efficacy of murine antibodies against human tumors in a
      human/mouse model system. Murine monoclonal anti-human antibodies may produce
      greater effects in human/mouse xenogeneic models, in which they are more likely
      to elicit host effector systems than when used in vivo in humans.

PMID- 8732693
TI  - Immunotherapy of established murine tumors with large multivalent immunogen and
      cyclophosphamide.
AB  - Plasma membrane vesicles isolated from tumor cells can be incorporated onto 5
      microns diameter microspheres and antigen in this form, termed large multivalent
      immunogen (LMI), augments generation of tumor-specific cytotoxic T lymphocyte
      (CTL) responses in vivo. Treatment of mice with LMI at the time of challenge with
      tumor significantly reduced growth of several tumors in their syngeneic hosts.
      Our report describes the effects of LMI on established progressing tumors,
      including P815 solid tumor and two fibrosarcomas in a lung-metastasis model.
      Treatment of mice bearing established tumors (7 to 12 days) with LMI alone did
      not significantly reduce tumor growth or extend host survival, but highly
      synergistic effects of combined treatment with cyclophosphamide (Cy) and LMI were
      found. Cy alone reduced the size of P815 solid tumors, but within a few days, the
      tumors began to grow progressively, and survival was only marginally extended.
      However, Cy followed 2 to 3 days later by a single injection of LMI resulted in
      prolonged reduction of tumor growth and significant extension of survival; in
      some experiments, tumors became undetectable in the majority of treated mice, and
      the mice survived indefinitely. Essentially the same results were obtained in
      experiments examining survival of mice bearing established MCA-203 fibrosarcoma.
      LMIs were uniquely effective in acting synergistically with Cy; antigen in the
      form of irradiated tumor cells or plasma membrane in adjuvant were ineffective,
      and free plasma-membrane antigen (not on microspheres) had only marginal effects.
      There has been considerable interest in the possibility of using tumor antigen to
      enhance tumor-specific immune responses, and clinical trials using this approach
      are showing some promise. The results described here suggest that altering the
      form of antigen by purifying plasma membranes and incorporating them onto
      microspheres might significantly improve the efficacy of tumor immunotherapy with
      antigen.

PMID- 8732694
TI  - Effective immunization against neuroblastoma using double-transduced tumor cells
      secreting GM-CSF and interferon-gamma.
AB  - Murine neuroblastoma, neuro-2a, was transduced with the retroviral vector MFG
      granulocyte-macrophage colony-stimulating factor (GM-CSF), to examine immune
      stimulation conferred by localized GM-CSF production. Expression of murine GM-CSF
      by neuro-2a (N-2a/GM) significantly reduced its tumorigenicity. Moreover,
      immunization of mice with irradiated N-2a/GM cells resulted in a significant
      protective effect against live tumor challenge 14 days later. Approximately 41%
      of mice immunized with irradiated N-2a/GM versus 0% of those vaccinated with
      irradiated parental tumor survived. Surviving mice were rechallenged after 50
      days with wild-type neuro-2a or with the Sa1 syngeneic sarcoma to discern whether
      the generated immunity was durable and tumor specific. All mice survived wild
      type neuro-2a challenge, whereas none survived inoculation with Sa1. Because both
      CD4+ and CD8+ T cells were necessary during priming to this MHC class Ilo, II
      tumor, these data indicate that major histocompatibility complex (MHC) class I+,
      II+ antigen-presenting cells (APCs) were required for the T-cell antitumor
      response. Co-expression of GM-CSF and IFN-gamma, both of which have
      immunostimulatory activities on antigen-presenting cells, abrogated the
      tumorigenic potential of this tumor and increased immunogenicity over N-2a/IFN
      but not N-2a/GM. Vaccination of mice with preexisting retroperitoneal tumors with
      irradiated N-2a/GM and irradiated N-2a/IFN/GM improved survival. There was a
      trend for nonirradiated transduced cells to be more immunogenic than their
      irradiated counterparts. Immunohistochemistry of tissues from the vaccination
      site revealed a pronounced macrophage infiltration associated with nonirradiated
      N-2a/GM and N-2a/IFN/GM. These data suggest that vaccination involving
      nonirradiated neuroblastoma cells transduced with genes that stimulate APCs may
      be a useful approach in stimulating antitumor T-cell responses.

PMID- 8732695
TI  - Treatment of oral cavity and oropharynx squamous cell carcinoma with
      perilymphatic interleukin-2: clinical and pathologic correlations.
AB  - We describe the correlations between the clinical and histologic findings in an
      initial series of 60 patients with T2-4, N0-3, M0 squamous cell carcinoma (SCC)
      of the oral cavity or oropharynx enrolled in a randomized trial set up to
      evaluate whether the disease-free interval and survival are extended when
      perilymphatic injections of recombinant interleukin-2 (rIL-2) are combined with
      routine surgery and radiotherapy. Twenty-nine patients were operated on only
      (controls). The other 31 received two daily injections of 2,500 U rIL-2, one near
      the mastoid process on the same side as the tumor and the other under the chin,
      for 10 days before surgery, and further injections on the nonoperated-on side on
      a monthly basis for 1 year starting 4 weeks after surgery (or radiotherapy, where
      necessary) in an effort to upregulate the immune system and delay recurrence.
      Their surgical specimens displayed a significantly greater inflammatory reaction,
      larger areas of necrosis, and more intense sclerosis. The inflammatory tumor
      infiltration consisted of eosinophils, plasma cells, and CD25+ and human
      leukocyte antigen (HLA)-DR+ lymphocytes. However, no correlations were apparent
      with regard to the intensity of necrosis, eosinophil infiltration, and the number
      of DR+ cells and the clinical outcome. By contrast, the correlation between CD25+
      cells and a significantly longer disease-free survival suggests that induction of
      T-cell reactivity, and perhaps specific immunity, is the only important aspect of
      rIL-2-induced antitumor reactivity.

PMID- 8732696
TI  - Isolated left ventricular filling abnormalities may predict interleukin-2-induced
      cardiovascular toxicity.
AB  - Interleukin-2 (IL-2) is a cytokine with proven activity against metastatic renal
      cell carcinoma (RCC) and malignant melanoma (MM). The intravenous administration
      of high-dose IL-2 is limited by important cardiovascular side effects such as
      hypotension, fluid retention, arrhythmias, and myocardial ischemia, which often
      cause dose reduction and/or treatment withdrawal. The occurrence of these toxic
      events is not predicted by routine pretreatment examinations. The aim of the
      present study was to test the reliability of serial echocardiography in
      predicting subsequent cardiac adverse effects in patients undergoing IL-2
      administration. In 19 patients (15 men, 4 women; median age: 51 years, range 27
      71 years; 10 affected by metastatic RCC and 9 affected by MM) we performed two
      dimensional and Doppler echocardiography before and immediately after 28
      continuous intravenous infusions (CIVI) of IL-2 at the dose of 18 MIU/m2/day for
      4 days. Left ventricular systolic function and the diastolic transmitral flow
      pattern were assessed before and after IL-2 administration. Significant changes
      of two indexes of left ventricular filling were noted: a decrease of the ratio of
      maximal flow velocity in early diastole to that in late diastole (E/A) (basal:
      1.12 +/- 0.46, mean +/- SD; posttreatment: 0.83 +/- 0.27; p < 0.01) and an
      increase of the percentage of the atrial contribution to left ventricular filling
      (basal: 37.75 +/- 11.58%; posttreatment: 49.43 +/- 16.48%; p < 0.01). Eight major
      cardiovascular events causing IL-2 infusion withdrawal were observed (two
      ischemic electrocardiographic modifications, three grade III-IV hypotension, one
      atrial fibrillation, one pericardial effusion, one acute heart failure). These
      major cardiovascular events were observed more often when an abnormal basal E/A
      ratio < 1.0 (p < 0.05) was found. We conclude that Doppler transmitral flow
      pattern analysis before and subsequent to IL-2 infusion is a useful and easily
      available procedure for the monitoring of cardiac modifications during CIVI IL-2
      administration. It might also predict a major cardiovascular event during IL-2
      administration. Patients with basal E/A ratio < 1.0 should be more carefully
      monitored during treatment and/or should be treated with lower IL-2 doses to
      avoid cardiovascular toxicity.

PMID- 8732697
TI  - Endocrine effects of IL-1 alpha and beta administered in a phase I trial to
      patients with advanced cancer.
AB  - Previous primate and rodent studies suggested that interleukin-1 alpha (IL-1
      alpha) caused changes in the secretion of pituitary, adrenal, thyroid, and
      gonadal hormones, as well as acute-phase reactants. Plasma samples were obtained
      after IL-1 alpha and beta treatment in cancer patients to document the changes in
      endocrine function suggested by the animal models. Successive groups of patients
      were treated at IL-1 alpha doses of 0.01, 0.03, 0.1, 0.3, and 1.0 microgram/kg,
      given daily as a 15-min intravenous bolus. IL-1 beta was given at 0.1
      microgram/kg by the same route and time course. After the first dose of IL-1,
      statistically significant elevations of a.m. and p.m. cortisol, growth hormone
      (GH), and prolactin (PRL) occurred. Thyroid-stimulating hormone (TSH) and C
      reactive protein (CRP) were elevated by the sixth treatment day. Testosterone
      decreased significantly in male patients. Follicle-stimulating hormone (FSH) and
      luteinizing hormone (LH) were more variable but decreased in most patients. The
      changes in cortisol, GH, PRL, TSH, CRP, FSH, LH, and testosterone resolved after
      treatment and did not result in clinically apparent endocrinopathies. Bolus doses
      of IL-1 alpha and beta cause significant changes in many endocrine laboratory
      parameters and influence the in vivo activities of multiple homeostatic endocrine
      functions in human beings.

PMID- 8732698
TI  - Natural immune reactivity-associated therapeutic response in patients with
      metastatic renal cell carcinoma receiving tumor-infiltrating lymphocytes and
      interleukin-2-based therapy.
AB  - Combination therapy with systemically administered interleukin-2 (IL-2) and tumor
      infiltrating lymphocytes (TIL) demonstrates significant clinical activity in some
      patients with metastatic renal cell carcinoma (RCC). The objective of this study
      was to identify predictors of therapeutic response in patients with IL-2- and TIL
      based immunotherapy. We characterized and compared immunologic properties of
      tumors, TILs, peripheral blood lymphocytes (PBLs) and sera of responding (R, n =
      8) with nonresponding patients (NR, n = 9). Before undergoing nephrectomy,
      responding patients exhibited a higher percentage of circulating natural killer
      (NK) cells (CD56+ CD3-) (43 +/- 20%) as compared with nonresponders (18 +/- 16%)
      (p < 0.01). After nephrectomy, the CD56+ CD3-/CD56- CD3+ ratio in responding
      patients (pre: 2.60 +/- 2.24; post: 0.28 +/- 0.19; p < 0.05) significantly
      decreased and was similar to that of patients not responding to therapy (0.42 +/-
      0.36). Sera from patients responding to immunotherapy, obtained before and after
      completion of therapy, contained natural killer (NK)-enhancing factor(s) that
      significantly enhanced the proliferation (3.2 x 10(3) +/- 25%/ 3.6 x 10(3) +/-
      13% counts/min) and cytotoxicity [17.6 +/- 4.0/18.0 +/- 1.9 lytic units (LU)] of
      fresh PBLs as compared with normal serum (1.8 x 10(3) +/- 8% counts/min; 13.4 +/-
      2.5 LU) or sera from nonresponders (1.6 x 10(3) +/- 25%/1.5 x 10(3) +/- 20%
      counts/min; 8.3 +/- 5.9/6.8 +/- 4.8 LU). In contrast to noncultured tumor
      suspension, IL-2 cultivation induced TIL growth, cytotoxicity, and multicytokine
      synthesis, and a complete clearance of tumor cells. No significant differences
      were observed between responders and nonresponders in the in vitro
      characteristics of tumor/TIL, which include the degree of intratumoral
      lymphocytic infiltrate, TIL expansion, specific lysis of autologous tumor,
      phenotype, expansion time, quantity of TIL infused, cytokine release, and degree
      of tumor aggressiveness. We conclude that clinical response to TIL and IL-2-based
      immunotherapy is associated with patients' baseline natural immune status. The
      percentage of circulating NK cells and the presence of serum NK-cell-enhancing
      factors may serve as potential predictors of response in patients with advanced
      RCC. The in vitro study of RCC-TIL suggests that activated TIL may provide a
      synergistic effect to that of administered IL-2 on activation of cellular immune
      response in situ, rendering a tumor eradication, while the clinical outcome is
      largely dependent on the pretreatment immune status of patient.

PMID- 8732699
TI  - Low-dose rIL-2-induced remission of disseminated CD30+ anaplastic large-cell
      lymphoma through reinforcement of presumed T-cell-mediated tumor cell killing,
      complicated by unilateral drowning of lymphoma-infiltrated lung.
AB  - We report on the immuno-oncologic analysis and treatment of a remarkable case of
      disseminated CD30+ anaplastic non-Hodgkin's lymphoma. Its clinical course was
      characterized by repeated spontaneous regressions, which were probably due to a T
      cell-mediated anti-lymphoma immune reaction, as tumor-infiltrating T lymphocytes
      were consistently observed in sections of lymphoma lesions and found to express
      high-affinity receptors for interleukin-2 (IL-2). This marker may be particularly
      suitable to predict a response to low-dose recombinant IL-2 (rIL-2), as confirmed
      in this case by prompt lymphoma regression after regional rIL-2 perfusion of a
      cutaneous lesion and by an impressive overall response to systemic rIL-2
      treatment. Despite the very low dose of rIL-2, 600,000 IU/24 h as a continuous
      i.v. infusion, systemic treatment was complicated by generalized capillary
      leakage and life-threatening unilateral drowning of the lymphoma-infiltrated left
      lung.

PMID- 8732700
TI  - Effectiveness of a behavioral weight control program for blacks and whites with
      NIDDM.
AB  - OBJECTIVE: To compare the weight losses of black and white patients with NIDDM
      treated in a year-long behavioral weight loss program. RESEARCH DESIGN AND
      METHODS: Subjects were randomly assigned to a behavioral program that either used
      a low-calorie diet throughout or included two 12-week periods of a very-low
      calorie diet (VLCD). Weight, dietary intake, and exercise were measured at 0, 6,
      and 12 months of treatment, and attendance and self-monitoring records were
      assessed weekly throughout the year. RESULTS: Blacks had smaller weight losses
      than whites regardless of treatment condition. Overall weight losses (baseline to
      1 year) were 7.1 kg in blacks vs 13.9 kg in whites. The differences in overall
      outcome resulted primarily from greater weight regain in blacks during months 6
      12 than in whites. There was a trend for blacks to have poorer attendance than
      whites during the latter half of the program and for blacks to report smaller
      changes in calorie intake from baseline to 6 months. CONCLUSIONS: The results
      confirm prior studies with nondiabetic patients showing smaller weight losses in
      blacks than in whites and suggest that these differences may result primarily
      from faster weight regain in blacks. Further research is needed to more carefully
      examine the variables that may explain this difference and to develop more
      effective programs for blacks with NIDDM.

PMID- 8732701
TI  - A metabolic syndrome in whites and African-Americans. The Atherosclerosis Risk in
      Communities baseline study.
AB  - OBJECTIVE: To describe clustering of hypertriglyceridemia, low HDL cholesterol,
      hypertension, diabetes, and hyperuricemia and its association with fasting
      insulin, waist-to-hip ratio (WHR), and BMI for African-American and white men and
      women. RESEARCH DESIGN AND METHODS: Observed frequencies of clusters were
      compared with those expected in 14,481 participants, 45-64 years of age, of the
      Atherosclerosis Risk in Communities (ARIC) baseline survey, 1987-1989.
      Associations of clusters with insulin, central adiposity, and overall obesity, as
      well as with abnormalities, were analyzed through multiple logistic regression.
      RESULTS: Clustering beyond chance was observed in all four sex/ethnic groups (P <
      0.001), with 7% of the sample presenting 30% of the abnormalities in large
      clusters (> or = 3 abnormalities per individual). The odds ratio (OR) for the
      association of each abnormality with clustering of the remaining four ranged from
      1.6 to 8.8 (P < 0.01). These odds of clustering were notably large in white
      women. Of the abnormalities, hypertriglyceridemia demonstrated the highest OR
      (5.0-8.8) and diabetes had the lower OR in African-American subjects than in
      white subjects (P < 0.001). Insulin, WHR, and BMI were statistically associated
      with clustering in all groups (P < 0.001, except for BMI in African-Americans.

PMID- 8732702
TI  - Socioeconomic status and clustering of cardiovascular disease risk factors in
      diabetic patients.
AB  - OBJECTIVE: Correction of cardiovascular risk factors is an essential component of
      good diabetes care. Our goal was to examine the relationship of socioeconomic
      status in five risk factors: obesity, hypertension, high cholesterol, smoking,
      and high HbA1c. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional
      prevalence study of all patients with diabetes (n = 1,553) attending a clinic in
      Glasgow, U.K. Area-based codes were used to measure socioeconomic status; these
      ranged from 1, the most affluent, to 7, the most deprived. RESULTS: Comparing
      patients with NIDDM from the seven categories of socioeconomic status, we found
      that those from deprived categories experienced a higher prevalence of obesity.
      In the most affluent groups, 30% had a BMI > 30 kg/m2 compared with 47% in the
      most deprived categories (P < 0.002). With regard to smoking, 13% in the most
      affluent category smoked compared with 33% in the most deprived (P < 0.001). In
      patients with IDDM from affluent categories, 13% smoked compared with 34% from
      deprived categories (P < 0.001). The proportion of patients with no cardiac risk
      factors fell by 30.6% from deprived category 1 to 7 (P < 0.001), and the
      proportion of patients with three or more risk factors rose from 8.6% in category
      1 to 20.2% in category 7. CONCLUSIONS: Diabetic patients from areas of low
      socioeconomic status are at increased risk of cardiovascular disease. To counter
      this, specific health education programs should be evolved and resources should
      be directed toward these areas.

PMID- 8732703
TI  - The relationship between socioeconomic status and diabetes control and
      complications in the EURODIAB IDDM Complications Study.
AB  - OBJECTIVE: To determine whether there are socioeconomic differences in diabetes
      control and complications in people with IDDM. RESEARCH DESIGN AND METHODS: We
      conducted a prevalence survey of 1,217 men and 1,170 women with IDDM age 25-60
      years from European clinics. Age at completion of education defined socioeconomic
      status: < or = 14 years defined those with primary education; 15-18 years, as
      secondary education; and > 19 years, as college education. Glycemic control,
      lipids, diet, retinopathy, neuropathy, and heart disease were assessed centrally.
      RESULTS: People with a primary education were older and had diabetes for longer
      than those with a college education. The mean percentage of HbA1c was worst in
      the primary-educated men (6.6 vs. 6.1%, P = 0.0007 for trend) and women (6.5 vs.
      6.0%, P = 0.0007). Total cholesterol level was higher in primary-educated than in
      college-educated men (5.6 vs 5.3 mmol/l, P = 0.002), as was triglyceride level
      (1.23 vs. 1.02 mmol/l, P = 0.0001). College-educated people were the least likely
      to be current smokers (P < 0.0001), and were most likely to partake in vigorous
      exercise (P < 0.001). Surprisingly, There was little difference in the prevalence
      of heart disease by educational status in men, while it was highest in the least
      educated women, but proliferative retinopathy was more common in primary- than in
      college-educated men (16 vs 10%, P = 0.04) as was macroalbuminuria (15 vs 9%, P =
      0.03). Glycemic control could not fully account for these differences.
      CONCLUSIONS: Healthy lifestyles are more prevalent in better educated men and
      women with IDDM, but these are not reflected in heart disease prevalence in men.
      The lower prevalence of severe microvascular complications in better educated
      men, unaccounted for by better glycemic control, requires further investigation.

PMID- 8732704
TI  - Trends in hospital admissions among children aged 0-19 years with type I diabetes
      in The Netherlands.
AB  - OBJECTIVE: To determine the number and duration of hospital admissions due to
      diabetes in children aged 0-19 years between 1980-1991. RESEARCH DESIGN AND
      METHODS: Secondary analysis of data collected by the SIG Health Care Information
      was based on the 9th revision of the International Classification of Diseases.
      The subjects were all children in The Netherlands, aged 0-19 years. The main
      outcome measures were number and duration of hospital admissions due to type I
      diabetes (ICD 9 code 250.0-250.9). RESULTS: The hospital admission rate due to
      diabetes decreased > 30%. This decrease was statistically significant in all age
      subgroups. The total number of days in hospital due to diabetes decreased
      dramatically: from 24,961 in 1980 to 11,305 in 1991. The average duration of
      hospital stay length due to diabetes decreased as well from 14.5 days in 1980 to
      11.9 days in 1991. CONCLUSIONS: The hospital admission rate and the length of
      hospital stay for diabetes in children aged 0-19 years have decreased, in spite
      of an increasing incidence. The hospital admission rate may decrease still
      further if more children with newly diagnosed diabetes can be adequately managed
      by team management at home in the initial phase.

PMID- 8732705
TI  - Raised serum sialic acid concentration precedes onset of microalbuminuria in
      IDDM. A 10-year follow-up study.
AB  - OBJECTIVE: Elevated concentrations of serum sialic acid, a potent cardiovascular
      risk factor in the general population, have been found in patients with IDDM and
      microalbuminuria. We investigated whether a coincidence exists between the
      increase of sialic acid concentrations and albuminuria in the transition from
      normoalbuminuria to microalbuminuria. Furthermore, the predictability of
      increased sialic acid as well as von Willebrand factor (vWF) and total and HDL
      cholesterol concentrations in development of persistent microalbuminuria in IDDM
      was investigated. RESEARCH DESIGN AND METHODS: This 10-year prospective study was
      carried out in a cohort of 209 IDDM patients with normoalbuminuria at baseline.
      RESULTS: Of the cohort, 198 patients completed the follow-up period and 27
      developed persistent microalbuminuria (urinary albumin excretion rate [UAER] > or
      = 30 mg/24 h). A coincident increase of UAER and serum sialic acid concentration
      was seen before persistent microalbuminuria was diagnosed. Elevation of serum
      sialic acid concentrations in those who later developed microalbuminuria occurred
      3 years before the diagnosis of persistent microalbuminuria. Baseline serum
      sialic acid concentrations were significantly higher in the group of patients who
      later developed microalbuminuria than in the group who remained normoalbuminuric
      (2.02 +/- 0.41 vs. 1.85 +/- 0.31 mmol/l [means +/- SD], P < 0.05). Baseline serum
      sialic acid concentration correlated significantly with HbA1c, UAER, blood
      pressure, total cholesterol, HDL cholesterol, and vWF and was significantly
      predictive for development of microalbuminuria (hazards ratio [95% CI], 3.1 [1.2
      8.1]; P = 0.02) after adjustments for sex, duration of diabetes, smoking, blood
      pressure, vWF, total cholesterol, and HDL cholesterol. Adjustment for the effects
      of HbA1c and UAER, however, canceled out the predictive effect of serum sialic
      acid. CONCLUSIONS: UAER and serum sialic acid concentration increase
      coincidentally before the onset of persistent microalbuminuria. An increased
      serum sialic acid concentration is predictive for the onset of microalbuminuria
      independent of age, sex, diabetes duration, smoking, blood pressure, vWF, and
      total HDL cholesterol.

PMID- 8732706
TI  - Increased tissue factor pathway inhibitor activity in IDDM patients with
      nephropathy.
AB  - OBJECTIVE: Tissue factor pathway inhibitor (TFPI) is bound to vascular
      endothelium (presumably to heparan sulfate) and circulates in complex with plasma
      lipoproteins. It directly binds and inhibits factor Xa. The purpose of the study
      is to investigate whether plasma TFPI activity is altered in IDDM and nephropathy
      and to evaluate the possible determinants of the alteration. RESEARCH DESIGN AND
      METHODS: We assessed plasma concentration of TFPI (total, truncated, and domain 3
      TFPI) and plasma activity of factor Xa inhibition in nondiabetic control subjects
      (n = 22) and in IDDM patients with normoalbuminuria (urinary albumin excretion
      rate [UAE] < 30 mg/24h, n = 17), incipient nephropathy (UAE 30-300 mg/24 h, n =
      17), clinical nephropathy (UAE > 300 mg/24h, n = 25). RESULTS: Total, truncated,
      and domain 3 TFPI concentrations were increased in IDDm patients compared with
      those in control subjects and were more pronounced in IDDM patients with
      nephropathy. Plasma activity of factor Xa inhibition measured by HEPTEST
      (Haemachem, St. Louis, MO) assay was increased in IDDM patients, especially in
      those with nephropathy. TFPI-dependent factor Xa inhibition, obtained as the
      difference in clotting time with and without adding activity-neutralizing anti
      TFPI antibody to samples, was increased in IDDm patients with nephropathy. This
      was, however, not sufficient to inhibit the biological activity of factor Xa as
      demonstrated by increased levels of prothrombin fragment 1 + 2. LDL cholesterol
      and HbA1c were independently correlated to plasma TFPI. CONCLUSIONS: Inhibition
      of factor Xa activity is increased in IDDM patients with nephropathy, mainly
      because of increased plasma TFPI activity. The increased plasma TFPI activity in
      these patients may be associated with and regulated by LDL in plasma and
      metabolic control. The anticoagulant activity of TFPI may attenuate the
      hypercoagulable state in diabetes but does not seem to be able to normalize
      hemostasis.

PMID- 8732707
TI  - No association between the Gly971Arg variant of the insulin receptor substrate 1
      gene and NIDDM in the Taiwanese population.
AB  - OBJECTIVE: To study the role of the Gly971Arg variant of the insulin receptor
      substrate 1 (IRS-1) gene in the development of NIDDM in the Chinese population
      living in Taiwan. RESEARCH DESIGN AND METHODS: A total of 82 unrelated normal
      control subjects, 89 subjects with NIDDM, and 23 multiplex families were
      recruited in Taiwan. All of them were Han Chinese. Pedigree members without a
      history of diabetes were studies by the standard 75-g oral glucose tolerance
      test. Detection of the Gly971Arg variant of the IRS-1 gene was performed by
      polymerase chain reaction and restriction fragment-length polymorphism analysis.
      RESULTS: The frequency of Gly971Arg variant of the IRS-1 gene in the normal
      population was 1.2% which was lower than frequencies reported in white
      populations. The prevalence of the Gly971Arg variant was not significantly
      increased in both the nonselected NIDDM population (1.1%) and the probands of the
      multiplex families (4.3%). More importantly, the Gly971Arg variant of the IRS-1
      gene did not cosegregate with BMI and NIDDM in these families, CONCLUSIONS: The
      Gly971Arg variant of the IRS-1 gene is an infrequent normal allele among
      Taiwanese. This variant is neither associated nor cosegregated with NIDDM in the
      Taiwanese population and families. Gly971Arg of IRS-1 gene does not play an
      important role in the development of NIDDM in this population.

PMID- 8732708
TI  - GHb is a better predictor of cardiovascular disease than fasting or postchallenge
      plasma glucose in women without diabetes. The Rancho Bernardo Study.
AB  - OBJECTIVE: To examine the relation between GHb, fasting plasma glucose (FPG),
      postchallenge plasma glucose (PCPG), and mortality from cardiovascular disease
      (CVD) and ischemic heart disease (IHD) in older adults. RESEARCH DESIGN AND
      METHODS: A community-based study of 1,239 nondiabetic older adults followed for
      an average of 8 years, from baseline (1984-1987) to 1993. RESULTS: GHb, but not
      FPG or PCPG, was significantly related to CVD and IHD mortality in women but not
      men. The age-adjusted relative hazard for those in the highest quintile of GHb (>
      or = 6.7%) compared with women with lower levels was 2.37 for fatal CVD (95% CI =
      1.30-4.31, P = 0.005) and 2.43 for IHD (95% CI = 1.12-5.25, P = 0.024). This
      association persisted after adjustment for all covariates (age, systolic blood
      pressure, BMI, LDL, HDL, triglycerides, cigarette smoking, antihypertensive
      medication use, and estrogen use). GHb was significantly associated with LDL and
      HDL levels in women, but the association between GHb and CVD or IHD persisted
      after adjustment for these lipoproteins. CONCLUSIONS: We concluded that GHb is a
      better predictor of CVD and IHD mortality than FPG or PCPG in women without
      diabetes; no single measure of glycemia was predictive in men. The reason for the
      sex difference is unexplained.

PMID- 8732709
TI  - A case-control study of diet in newly diagnosed NIDDM in the Wanigela people of
      Papua New Guinea.
AB  - OBJECTIVE--To study the association between diet and newly diagnosed NIDDM in the
      Wanigela people of Papua New Guinea, a population with an extraordinary
      susceptibility for NIDDM. RESEARCH DESIGN AND METHODS--We performed a case
      control study of Wanigela people from an urban settlement (Koki). Case patients
      (n = 145) were asymptomatic subjects in whom NIDDM was newly diagnosed using a 2
      h 75-g oral glucose tolerance test. Control subjects with glucose tolerance (n =
      140) were group-matched on the basis of age and sex. A detailed food frequency
      questionnaire was used to determine energy and nutrient intakes. Nutrient intakes
      were compared directly and after calculation of residuals to correct for energy
      intake. Odds ratios for NIDDM were computed in relation to total energy and
      specific nutrient intakes, adjusting for age, sex, BMI, waist-to-hip ratio, and
      physical activity. RESULTS--There were no differences between case patients and
      control subjects in mean values of total energy-adjusted nutrient intakes. In
      logistic regression models, neither total energy nor any specific nutrients were
      associated with increased risk of NIDDM. When models were repeated with nutrients
      categorized by textiles, there were marginally significant associations with
      intakes of fiber (positive) and cholesterol, protein, and sugar (negative).
      CONCLUSIONS--This study does not support the hypothesis that saturated fat is an
      independent risk factor for NIDDM. The weak associations of intakes of fiber and
      cholesterol with newly diagnosed NIDDM were in the opposite directions to those
      expected and are probably due to chance. Relative homogeneity of diet within a
      community, such as that found in Koki, makes it difficult to demonstrate risk
      factor-disease associations. However, changes in diet and reduced levels of
      physical activity accompanying urbanization undoubtedly contribute to the high
      prevalence of obesity observed in this community, and hence diet is likely to
      contribute to NIDDM risk at least by indirect means.

PMID- 8732710
TI  - A comparison of the effects of n-3 fatty acids from linseed oil and fish oil in
      well-controlled type II diabetes.
AB  - OBJECTIVE: Supplementation of type II diabetic diets with n-3 fatty acids (FAs)
      from fish oil (FO) has been associated with lowered triglyceride and VLDL levels,
      although reports of impaired glycemic control have limited their use. Effects of
      n-3FAs from nonmarine sources are less well documented. Therefore, an
      investigation comparing the effects of linseed oil (LO) with FO supplementation
      was undertaken in subjects with type II diabetes. RESEARCH DESIGN AND METHODS:
      Eleven subjects with type II diabetes were given supplements with LO and FO for 3
      months each in a randomized double-blind crossover fashion after 3 months of
      olive oil placebo. Oils were given as 35 mg FA.kg body wt-1.day-1. After each 3
      month period, fasting glucose and insulin levels, HbA1c, lipid profiles, insulin
      sensitivity (SI), glucose effectiveness (SG), and acute insulin response to
      glucose (AIRG) were evaluated. RESULTS: HbA1c and lipid values were within the
      normal range at randomization. Repeated measures analysis of variance testing
      found no significant differences in weight; fasting glucose and insulin levels;
      HbA1c; total, LDL, and HDL cholesterol levels; SI; SG; or AIRG with either active
      oil. FO was associated with significant reductions in triglycerides and a trend
      toward decreased SI. CONCLUSIONS: In a population with well-controlled type II
      diabetes, 3 months of FO but not LO resulted in lowered triglyceride levels.
      Neither LO nor FO significantly affected glycemic control, cholesterol values,
      SG, or insulin secretion, while a nonsignificant trend toward decreased insulin
      sensitivity was found with FO.

PMID- 8732711
TI  - Rapid gastric emptying of a solid pancake meal in type II diabetic patients.
AB  - OBJECTIVE: To estimate the rate of gastric emptying of a solid pancake
      carbohydrate meal in recently diagnosed asymptomatic type II diabetic patients
      compared with nondiabetic control subjects. RESEARCH DESIGN AND METHODS: Gastric
      emptying studies using radiolabeled meals were performed on eight recently
      diagnosed asymptomatic diabetic patients and on eight sex-, BMI- and age-matched
      nondiabetic control subjects. Although a liquid protein drink was administered
      along with the pancake meal, the radioactivity was adherent to only the pancake
      portion of the meal. Plasma glucose and serum insulin levels were measured in
      fasting and postprandial blood samples collected at 15-min intervals up to 120
      min after ingestion of the mixed nutrient meal. RESULTS: The average gastric half
      emptying time (time it takes for one-half of the meal to empty) was significantly
      more rapid for the diabetic patients (45.3 +/- 4.8 min) when compared with the
      nondiabetic control subjects (60.4 +/- 5.1 min; P = 0.05). The serum insulin
      concentrations were not statistically different between the two groups. Plasma
      glucose values were significantly higher in the diabetic patients compared with
      the nondiabetic control subjects. CONCLUSIONS: Type II diabetic patients with no
      clinical evidence of neuronal dysfunction have a significantly more rapid rate of
      gastric emptying of a solid high-carbohydrate meal when compared with nondiabetic
      control subjects.

PMID- 8732712
TI  - Risk factors for diabetes and cardiovascular disease in young Australian
      aborigines. A 5-year follow-up study.
AB  - OBJECTIVE: To test the hypothesis that hyperinsulinemia and glucose intolerance
      are present at an early age in australian aborigines and can be used to predict
      the eventual development of NIDDM. RESEARCH DESIGN AND METHODS: Baseline
      anthropometric, pubertal stage, and blood pressure data were collected for 100
      Australian aboriginal children and adolescents in 1989. Plasma concentrations of
      glucose, insulin, C-peptide, triglycerides, and LDL, HDL, and total cholesterol
      were measured before and during an oral glucose tolerance test. All measurements
      were repeated in 74 individuals from the original study population in 1994.
      Results were compared among hyperinsulinemic and normoinsulinemic subjects, and
      subjects with normal or abnormal glucose tolerance. RESULTS: The percentage of
      subjects who were overweight increased from 2.7% at baseline to 17.6% 5 years
      later. At a mean age of 18.5 years, 8.1% of the population had impaired glucose
      tolerance (IGT), 2.7% had diabetes, and 21.6% had elevated cholesterol
      concentrations in plasma. Dyslipidemia was particularly prevalent among male
      subjects in the population: 34.4% had elevated plasma cholesterol and 21.9% had
      elevated LDL cholesterol values. Of the eight subjects who had diabetes or IGT in
      1994, four were classified as hyperinsulinemic in 1989 and four were not.
      CONCLUSIONS: The major finding of this study is the high prevalence of risk
      factors for NIDDM and cardiovascular disease in this population of aboriginal
      children and adolescents. Abnormalities of carbohydrate and lipid metabolism were
      well established by late in the second decade of life. Although many subjects had
      high insulin levels and there was evidence of insulin resistance in the
      population, hyperinsulinemia did not predict the development of abnormal glucose
      tolerance 5 years later.

PMID- 8732713
TI  - Can postmenopausal hormone replacement improve plasma lipids in women with
      diabetes? The Atherosclerosis Risk in Communities Study Investigators.
AB  - OBJECTIVE: to evaluate the association of postmenopausal hormone replacement with
      plasma lipids in diabetic women. RESEARCH DESIGN AND METHODS: Cross-sectional
      data from a multiracial population study were used to evaluate the relationship
      of hormone replacement status with plasma lipids in diabetic (n = 694) versus
      nondiabetic (n = 5,321) postmenopausal women. RESULTS: Although diabetic women
      who currently used hormone replacement had higher adjusted mean HDL cholesterol
      levels than those who did not (56.9 vs. 53.6 mg/dl), they had proportionately
      lower hormone-related increases in HDL, HDL2, and HDL3 cholesterol than did
      nondiabetic women (HDL cholesterol 64.9 [current users] vs. 55.7 mg/dl [those who
      never used hormones]). There was a trend toward greater triglyceride values with
      hormone replacement in diabetic women (156.6 [current users] vs. 125.4 mg/dl
      [those who never used hormones]) than in nondiabetic women (143.3 [current users]
      vs. 123.7 mg/dl [those who never used hormones]). LDL cholesterol and
      apolipoprotein B levels were lower and apolipoprotein A-I levels were higher with
      hormone replacement, to a similar degree in diabetic and nondiabetic women.
      CONCLUSIONS: Diabetic women appear to have a blunted response to the HDL-raising
      effects of estrogen and an exaggerated hypertriglyceridemic response. This may
      result in attenuated cardioprotection from postmenopausal hormone replacement
      therapy and potentially an increased risk of acute pancreatitis from
      hypertriglyceridemia. The risks and benefits of postmenopausal hormone
      replacement need to be carefully weighed in diabetic women.

PMID- 8732714
TI  - Evolution, risk factors, and prognostic implications of albuminuria in NIDDM.
AB  - OBJECTIVE: To study the cumulative incidence of albuminuria and its determinants
      in NIDDM patients and nondiabetic subjects from the diagnosis and impact of
      albuminuria on cardiovascular mortality. RESEARCH DESIGN AND METHODS: We
      performed a 10-year prospective observational study of 133 well-characterized
      middle-aged patients with newly diagnosed NIDDM and 144 control subjects. Both
      groups were examined at baseline and after 5 and 10 years. Urinary albumin
      excretion was determined from timed 24-h (baseline and 5-year examinations) or
      overnight samples (10-year examination). Microalbuminuria was defined as urinary
      albumin excretion of 30-300 mg/24 hr or 20-200 micrograms/min, with the higher
      values considered as macroalbuminuria. RESULTS: The cumulative incidence of micro
      and macroalbuminuria increased sharply after 5 years in NIDDM patients
      (baseline: 18.2 and 3.0%; 5 years: 18.9 and 1.8%; and 10 years: 33.0 and 10.2%)
      but markedly less in control subjects (baseline: 1.4 and 0%, P < 0.001 for
      diabetic patients vs. control subjects for any albuminuria; 5 years: 6.0 and
      0.8%, P < 0.01; 10 years: 11.9 and 0.8%, P < 0.001). The most important
      determinant of the development of albuminuria was the metabolic control of
      diabetes in NIDDM patients during the follow-up, whereas in nondiabetic subjects,
      the development of albuminuria was related to elevated blood pressure and fasting
      insulin levels. Baseline and 5-year albuminuria predicted subsequent
      cardiovascular mortality in diabetic patients, even when adjusted for multiple
      risk factors. The risk of cardiovascular death in NIDDM patients increased by
      simultaneous occurrence of hyperinsulinemia and albuminuria. CONCLUSIONS: The
      frequency of microalbuminuria in patients with NIDDM increases sharply with the
      duration of diabetes. Chronic hyperglycemia is the main risk factor for
      microalbuminuria in diabetic patients. Microalbuminuria accompanied by
      hyperinsulinemia is a powerful predictor of cardiovascular death in NIDDM
      patients.

PMID- 8732715
TI  - Structure and costs of health care of diabetic patients in Finland.
AB  - OBJECTIVE: The aim of the present study was to examine both the structure,
      including modes of drug treatment, ambulatory care, and hospital inpatient care,
      and the costs of health care for drug-treated diabetic patients in Finland.
      RESEARCH DESIGN AND METHODS: The modes of drug treatment and ambulatory care were
      studied with the help of a questionnaire given to all diabetic patients obtaining
      their medication through pharmacies in Finland during a 7-week period in 1989.
      The questionnaire sought information on drug treatment, site of health care, and
      frequency of visits to physicians. Hospital inpatient care was evaluated by
      linking the patient data from the Hospital Discharge Register and the Central
      Drug Register. The direct costs of health care were calculated by using relevant
      average costs. RESULTS: A total of 30,266 questionnaires were returned,
      representing > 70% of all drug-treated diabetic patients receiving medication in
      the period studied. Of the diabetic patients, 63% were treated by oral medication
      only, 31% by insulin only, and 6% by a combination of insulin and oral agents. Of
      the patients in whom diabetes was diagnosed at > or = 30 years of age, 75% were
      treated at health centers, whereas > 60% of those in whom diabetes was diagnosed
      at < 30 years of age were treated at outpatient clinics. The mean annual
      frequency of visits was 4.0 for patients receiving insulin treatment and 3.3 for
      patients receiving treatment with oral medications. The diabetic patients used
      1.5 million hospital inpatient days per year, which was 13% of the total
      inpatient days in Finland. Of the inpatient days, 20% were for diabetes as the
      principal cause, 52% for diabetes-related diseases, and 28% for causes unrelated
      to diabetes. The direct costs of the health care of drug-treated diabetic
      patients in 1989 were 5.8% of the total costs of health care in Finland and were
      three times higher than the average costs of care for nondiabetic individuals.
      The direct costs were divided into inpatient care (81%), medication (9%),
      ambulatory care (8%), and self-care equipment (2%). CONCLUSIONS: Hospital
      inpatient care is the major contributor to the excess of health care expenditures
      for diabetic patients.

PMID- 8732716
TI  - Does a high-carbohydrate diet have different effects in NIDDM patients treated
      with diet alone or hypoglycemic drugs?
AB  - OBJECTIVE: To compare the effects of a nigh-carbohydrate diet on blood glucose
      and plasma lipids in NIDDM patients with either mild or severe glucose
      intolerance. RESEARCH DESIGN AND METHODS: A crossover design with a 15-day
      intervention diet was used. Eighteen patients were separated into two groups on
      the basis of hypoglycemic treatment (diet, n = 9, or diet plus glibenclamide, n =
      9) and were assigned to a 15-day treatment with a high-carbohydrate/low-fiber
      diet containing 60% energy from carbohydrate and 20% from fat or a low
      carbohydrate/low-fiber diet with 40% energy from carbohydrate and 40% from fat
      and then crossed over to the other diet for 15 more days. RESULTS: The high
      carbohydrate diet produced a significant increase in postprandial blood glucose
      in patients on glibenclamide (13.6 +/- 1.4 vs. 11.0 +/- 1.8 mmol/l, P < 0.002,
      while no difference was recorded in the group on diet alone (9.7 +/- vs. 8.9 +/-
      0.6 mmol/l). Postprandial insulin levels were significantly higher after the high
      carbohydrate diet in the group on diet along (248 +/- 32 vs. 192 +/- 28 pmol/l, P
      < 0.01), while no significant differences were observed in the other group (226
      +/- 19 vs. 202 +/- 24 pmol/l) The high-carbohydrate diet also induced a
      significant increase in fasting plasma triglyceride concentrations in both groups
      (1.36 +/- 0.2 vs. 1.12 +/- 0.2 mmol/l, P < 0.05 and 1.4 +/- 0.3 vs. 1.1 +/- 0.1
      mmol/l, P < 0.05). No differences were observed in fasting plasma cholesterol and
      HDL. CONCLUSIONS: The effects of the high-carbohydrate diet on blood glucose
      control in NIDDM patients differ according to severity of glucose intolerance.

PMID- 8732717
TI  - A family history of NIDDM is associated with decreased aortic distensibility in
      normal healthy young adult subjects.
AB  - OBJECTIVE: NIDDM is associated with stiffer arteries and an increased incidence
      of macrovascular disease. NIDDM has strong familial inheritance. We studied the
      associations of a family history of NIDDM with blood pressure-corrected aortic
      distensibility (Cp). RESEARCH DESIGN AND METHODS: Because age is a strong
      determinant of arterial distensibility, we studied an age-select cohort of 67
      healthy normotensive normoglycemic young adults along with fasting measurements
      of glucose and insulin concentrations. Cp was calculated from noninvasive Doppler
      ultrasound measurements of pulse wave velocity along the descending
      thoracoabdominal aorta. RESULTS: The mean age of the subjects was 20.6 +/- 0.7
      (mean +/- SD) years. A total of 22 subjects gave a positive family history of
      NIDDM in a parent or grandparent. Subjects with a positive family history of
      NIDDM had significantly less distensible (i.e., stiffer) aortas than their age-
      and sex-matched counterparts who gave no family history of NIDDM (Cp
      [dimensionless]: 0.22 +/- 0.04 vs. 0.25 +/- 0.04, P = 0.02). Subjects with a
      positive family history of NIDDM also had significantly higher fasting glucose
      (5.1 +/- 0.4 vs. 4.9 +/- 0.4 mmol/l, P = 0.009) and insulin (7.5 +/- 5.5 vs. 4.2
      +/- 2.0 mU/l, P = 0.02) levels and BMIs (23.2 +/- 2.3 vs 21.1 +/- 2.5 kg/m2, P =
      0.002). On multivariate regression analysis, family history of NIDDM (P = 0.03)
      was the only significant independent predictor of Cp. CONCLUSIONS: A positive
      family history of NIDDM is associated with decreased aortic distensibility in
      early adult life. The relevance of these observations to future cardiovascular
      events merits further investigation.

PMID- 8732718
TI  - Endogenous insulin modulates circulating endothelin-1 concentrations in humans.
AB  - OBJECTIVE: To assess the effect of oral glucose loading on plasma endothelin-1
      (ET-1) levels in humans. RESEARCH DESIGN AND METHODS: A total of 75 g D-glucose
      was given orally to 14 nonobese nondiabetic essential hypertensive subjects
      (eight men and six women, mean age 43.1 +/- 3.0 years) and eight normotensive
      subjects (four men and four women, mean age 45.2 +/- 4.1 years). Blood samples
      for plasma ET-1 measurement were drawn every 30 min for 2 h and then at 180 and
      240 min. RESULTS: After glucose load, insulin increased more significantly in
      hypertensive subjects than in normotensive subjects at times 60 (P = 0.004) and
      90 (P = 0.001) min. Glucose loading was followed by a mild but significant
      increase in circulating ET-1 levels in both groups (hypertensive subjects, from
      0.87 +/- 0.25 pg/ml at time 0 to 1.64 +/- 0.33 pg/ml at 120 min and 1.74 +/- 0.38
      pg/ml at 180 min, P < 0.05; normotensive subjects, from 0.82 +/- 0.38 pg/ml at
      time 0 to 1.42 +/- 0.18 pg/ml at 180 min, P < 0.05). Whereas baseline ET-1 levels
      were similar between the two groups, postload ET-1 levels were higher in
      hypertensive subjects than in normotensive subjects (P = 0.003 at 120 min; P =
      0.04 at 180 min). CONCLUSIONS: This study indicates that significant changes in
      circulating ET-1 levels occur after oral glucose loading, probably due to a
      glucose-induced increment in endogenous insulin concentration.

PMID- 8732719
TI  - Role of mitochondrial DNA tRNA leucine and glucagon receptor missense mutations
      in Utah white diabetic patients.
AB  - Recently, subtypes of typical NIDDM were suggested based on missense mutations of
      mitochondrial DNA [tRNALeu(UUR)] and the glucagon receptor gene (Gly40Ser).
      Together these mutations might explain NIDDM in 5--8% of patients. To test the
      hypothesis that these mutations play an important role in a Northern European
      population with a strong family history of diabetes, we screened members of 45
      families selected for having two or more diabetic siblings and 62 additional
      unrelated diabetic individuals for both mutations. We also examined 74
      nondiabetic control subjects. Mitochondrial DNA mutations were not detected
      despite our ability to detect as little as 3% heteroplasmy in a sample from an
      individual known to carry the mutation. Likewise, the glucagon receptor Gly40Ser
      mutation was present in a single diabetic patient who on subsequent investigation
      was of Italian descent. Thus, neither subtype of NIDDM is present in the Utah
      diabetic population, which is reflective of other Northern European populations.

PMID- 8732720
TI  - Alcohol and the NIDDM patient.
AB  - Historically, alcohol use by the diabetic patient has been controversial. Recent
      studies in the general population have shown an improvement in mortality with
      moderate alcohol intake (one to three drinks per day). This improved mortality is
      greatest in those individuals who have a higher risk of ischemic heart disease.
      The mechanisms of the beneficial effects of alcohol include positive effects on
      insulin resistance, HDL cholesterol, platelet aggregation, and fibrinolysis.
      Since the diabetic patient has an especially high risk of ischemic heart disease
      because of these factors, the use of a moderate amount of alcohol should not be
      discouraged. The short-term risks of heavy or continuous alcohol intake include
      hypoglycemia, glucose intolerance, and ketone and lactate accumulation. In the
      long term, heavy alcohol intake is associated with an increased prevalence of
      cancer, hypertension, cirrhosis of the liver, and symptomatic neuropathy.
      Moderate alcohol intake taken with a meal has been shown to have little or no
      effect on postprandial glycemic excursions.

PMID- 8732721
TI  - Pre-conception care of diabetes, congenital malformations, and spontaneous
      abortions.

PMID- 8732722
TI  - Orthostatic hypotension in poorly regulated NIDDM.

PMID- 8732723
TI  - A pitfall in the association study of ACE gene polymorphism.

PMID- 8732724
TI  - Pancreatic polypeptide responses to hypoglycemia in aging and diabetes.

PMID- 8732725
TI  - Latex allergen allergic reactions.

PMID- 8732726
TI  - Gly40Ser substitution in the glucagon receptor is rarely involved in the
      pathogenesis of NIDDM in Japanese patients.

PMID- 8732727
TI  - Prevalence of NIDDM in indigenous communities of Durango, Mexico.

PMID- 8732728
TI  - 1995 EASD meetings. Immunology, insulin, amylin, obesity, retinopathy, and
      neuropathy.

PMID- 8732729
TI  - Cost-effective therapy for hypertension.
AB  - The costs of treating hypertension are out of control. The Joint National
      Committee on the Detection, Evaluation, and Treatment of High Blood Pressure and
      others recommend the use of diuretics and beta-blockers as first-line agents.
      Newer drugs such as calcium channel blockers, alpha-blockers, and angiotensin
      converting-enzyme inhibitors have improved metabolic profiles, but have not been
      proved in long-term, randomized, controlled trials to reduce morbidity and
      mortality. Our General Medicine Clinic has gradually shifted toward prescribing
      the newer agents. We reviewed our drug use, evaluated the literature, and made
      recommendations in the form of guidelines. Clinicians' concerns included quality
      of-life issues, sexual dysfunction, metabolic changes--lipids, potassium, insulin
      resistance--and others. These concerns were addressed, and a consensus was
      reached. Our goal is to streamline therapy, reduce costs, and provide proven
      effective medication.

PMID- 8732730
TI  - Alpine skiing injuries. A nine-year study.
AB  - Injury patterns in alpine skiing have changed over time as ski, boot, binding,
      and slope-grooming technologies have evolved. We retrospectively examined injury
      patterns in alpine skiers over a 9-year period at the Mammoth and June mountains
      (California) ski area. A total of 24,340 injuries were reported for the 9 seasons
      studied, and total lift tickets sold numbered 9,201,486. The overall injury rate
      was 2.6 injuries per 1,000 skier days and increased slowly over the period
      studied. The knee was the most frequently injured area at 35% of all injuries.
      Increasing trends (P < .05) were noted for the rates of lower extremity injuries
      (37%) and knee injuries (45%). A decreasing trend was noted for the rate of
      lacerations (31% decrease). Slight increases were noted in upper extremity and
      axial injury rates. Skiing injuries continue to be a worrisome recreational
      problem despite improvements in ski equipment and slope-grooming techniques. The
      increasing trend in lower extremity, particularly knee, injury rates highlights
      the need for continued skier education and equipment innovation.

PMID- 8732731
TI  - Preeclampsia. Still an enigma.

PMID- 8732733
TI  - Endemic mycosis complicating human immunodeficiency virus infection.
AB  - Persons infected with the human immunodeficiency virus are prone to the
      development of many fungal diseases. Normal hosts with intact immunity usually
      recover from infection by these less-invasive fungi. In persons with compromised
      T-cell-mediated immunity, however, widespread dissemination from a pulmonary
      focus occurs. In this review, we discuss the epidemiology, clinical
      manifestations, diagnosis, and treatment of the three major North American
      mycoses, histoplasmosis, blastomycosis, and coccidioidomycosis. In most cases,
      amphotericin B is the initial drug of choice, followed by one of the azoles for
      lifelong maintenance therapy.

PMID- 8732732
TI  - Cystic fibrosis in adults. From researcher to practitioner.
AB  - The Cystic Fibrosis Foundation currently tracks about 20,000 Americans with
      cystic fibrosis, an autosomal recessive genetic disease that leads to multisystem
      complications. With the institution of better therapeutic regimens over the past
      2 decades, more patients with this disease are surviving to adulthood. Within the
      past decade, both clinical and basic science research in the field of cystic
      fibrosis has progressed at a rapid rate. The intent of this review is to
      introduce readers to the molecular, cellular, and systemic disorders of this
      disease. We discuss treatment strategies involving antibiotics, nutrition, immune
      response mediators, chest physiotherapy, and sputum-active agents with respect to
      the airway dysfunction of cystic fibrosis. Other common complications, recent
      developments, transplantation, and gene therapy are also reviewed.

PMID- 8732734
TI  - Laser treatment of genital condylomata acuminata.

PMID- 8732735
TI  - Should we and can we cure prostate cancer?

PMID- 8732736
TI  - Laparoscopic Burch bladder neck suspension.

PMID- 8732737
TI  - Laparoscopic orchiopexy for intraperitoneal testicles.

PMID- 8732738
TI  - Managing ureteral calculi.

PMID- 8732739
TI  - Surgical treatment of Peyronie's disease.

PMID- 8732740
TI  - Serologic markers in prostate cancer.

PMID- 8732741
TI  - New options for managing severe oligospermia and azoospermia.

PMID- 8732742
TI  - Retrospective diagnosis of a fatal case of the hantavirus pulmonary syndrome,
      1980.

PMID- 8732743
TI  - Treatment of a patient with an undefined hypercoagulable state with long-term low
      molecular-weight heparin.

PMID- 8732744
TI  - Bartender's hand an unusual form of occupational cumulative trauma disorder.

PMID- 8732745
TI  - Clinical breast examination.
AB  - An astute clinician has an appreciation of the wide variation possible in normal
      breasts, but anticipates that the palpation of the breasts of an individual woman
      will be determined by basic facts concerning typical relative distribution of
      gland tissue, breast symmetry, the influence of life history, and possibly
      previous surgery. If the findings of a CBE are not as anticipated, the clinician
      must find out why this is so. This is a different frame of reference from asking
      whether a given lump or area should be considered suspicious for cancer. The
      basic questions are whether the findings of a CBE are consistent with typical
      breast structure and anatomy and in the context of the woman's life history. If
      these questions can be answered in the affirmative, the examination is complete;
      if not, further evaluation is necessary.

PMID- 8732746
TI  - Lighting and fattening--evolving concepts in the pathogenesis of preeclampsia.

PMID- 8732747
TI  - Cystic fibrosis therapy--where we are and how we got there.

PMID- 8732748
TI  - Can the Ottawa ankle decision rules be applied in the United States?

PMID- 8732749
TI  - The role of hyperbaric oxygenation therapy for necrotizing fasciitis.

PMID- 8732750
TI  - Latino belief of alleged medical procedure.

PMID- 8732751
TI  - Expiry date display on drug packages.

PMID- 8732752
TI  - Probing the tertiary structure of proteins by limited proteolysis and mass
      spectrometry: the case of Minibody.
AB  - A strategy that combines limited proteolysis experiments and mass spectrometric
      analysis of the fragments generated has been developed to probe protease
      accessible sites on the protein surface. This integrated approach has been
      employed to investigate the tertiary structure of the Minibody, a de novo
      designed 64-residue protein consisting of a beta-sheet scaffold based on the
      heavy-chain variable-domain structure of a mouse immunoglobulin and containing
      two segments corresponding to the hypervariable H1 and H2 regions. The low
      solubility of the protein prevented a detailed characterization by NMR and/or X
      ray. Different proteases were used under strictly controlled conditions and the
      cleavage sites were mapped onto the anticipated Minibody model, leading to the
      identification of the most exposed regions. A single-residue mutant was
      constructed and characterized, following the same procedure, showing a slightly
      higher correspondence with the predicted model. This strategy can be used to
      effectively supplement NMR and X-ray investigations of protein tertiary
      structure, where these procedures cannot provide definitive data, or to verify
      and refine protein models.

PMID- 8732753
TI  - Sequence replacements in the central beta-turn of plastocyanin.
AB  - The role of beta-turns in dictating the structure of a beta-barrel protein is
      assessed by probing the tolerance of the central beta-turn of poplar plastocyanin
      to substitution by arbitrary sequences. Native plastocyanin binds copper and is
      colored bright blue. However, when the wild-type Pro47-Ser48-Gly49-Val50 turn
      sequence is replaced by arbitrary tetrapeptides, the vast majority (92/98 = 94%)
      of mutant proteins cannot fold into the native blue structure. Characterization
      of the colorless mutant proteins demonstrates that the majority of substitutions
      in this type II beta-turn disrupt the native structure severely. Gross structural
      changes are indicated by major differences in the CD spectra of the mutants
      relative to the wild-type protein, and by the much larger apparent size of mutant
      proteins in gel filtration experiments. These mutant proteins do not bind copper.
      Furthermore, Cys84 forms a disulfide bond readily in the colorless mutant
      proteins, indicating that it has moved away from the buried position it occupies
      in the native copper binding site and has become exposed. These results indicate
      that the central beta-turn in plastocyanin is not merely a default structure
      arising in response to the surrounding context; rather, sequence information in
      this turn plays an active role in dictating the location of a chain reversal in
      the beta-barrel structure. These findings are discussed in terms of their
      implications for the folding of natural proteins, as well as the design of de
      novo proteins.

PMID- 8732754
TI  - Comparison of the structures of the cyclotheonamide A complexes of human alpha
      thrombin and bovine beta-trypsin.
AB  - Thrombin, a trypsin-like serine protease present in blood, plays a central role
      in the regulation of thrombosis and hemostasis. A cyclic pentapeptide,
      cyclotheonamide A (CtA), isolated from sponges of the genus Theonella, inhibits
      thrombin, trypsin, and certain other serine proteases. Enzyme inhibition data for
      CtA indicate that it is a moderate inhibitor of alpha-thrombin (K(i) = 1.0 nM),
      but substantially more potent toward trypsin (K(i) = 0.2 nM). The comparative
      study of the crystal structures of the CtA complexes of alpha-thrombin and beta
      trypsin reported here focuses on structure-function relationships in general and
      the enhanced specificity of trypsin, in particular. The crystal structures of the
      CtA complexes of thrombin and trypsin were solved and refined at 1.7 and 2.0 A
      resolution, respectively. The structures show that CtA occupies the active site
      with the Pro-Arg motif positioned in the S2 and S1 binding sites. The alpha-keto
      group of CtA is involved in a tetrahedral intermediate hemiketal structure with
      Ser 195 OG of the catalytic triad and is positioned within bonding distance from,
      and orthogonal to, the re-face of the carbonyl of the arginine of CtA. As in
      other productive binding modes of serine proteases, the Ser 214-Gly 216 segment
      runs in a twisted antiparallel beta-strand manner with respect to the
      diaminopropionic acid (Dpr)-Arg segment of CtA. The Tyr 60A-Thr 60I insertion
      loop of thrombin makes a weak aromatic stacking interaction with the v-Tyr of CtA
      through Trp 60D. The Glu 39 Tyr and Leu 41 Phe substitutions in trypsin produce
      an enhanced aromatic interaction with D-Phe of CtA, which also leads to different
      orientations of the side chains of D-Phe and the v-Tyr. The comparison of the CtA
      complexes of thrombin and trypsin shows that the gross structural features of
      both in the active site region are the same, whereas the differences observed are
      mainly due to minor insertions and substitutions. In trypsin, the substitution of
      Ile 174-Arg 175 by Gly 174-Gln 175 makes the S3 aryl site more polar because the
      Arg 175 side chain is directed away from thrombin and into the solvent, whereas
      Gln 175 is not. Because the site is occupied by the Dpr group of CtA, the
      occupancy of the S3 site is better in trypsin than in thrombin. In trypsin, the D
      Phe side chain of CtA fits between Tyr 39 and Phe 41 in a favorable manner,
      whereas in thrombin, these residues are Glu 39 and Leu 41. The higher degree of
      specificity for trypsin is most likely the result of these substitutions and the
      absence of the fairly rigid Tyr 60A-Thr 60I insertion loop of thrombin, which
      narrows access to the active site and forces less favorable orientations for the
      D-Phe and v-Tyr residues.

PMID- 8732756
TI  - Purification and characterization of dihydroorotate dehydrogenase A from
      Lactococcus lactis, crystallization and preliminary X-ray diffraction studies of
      the enzyme.
AB  - Lactococcus lactis is the only organism known to contain two dihydroorotate
      dehydrogenases, i.e., the A- and B-forms. In this paper, we report the
      overproduction, purification, and crystallization of dihydroorotate dehydrogenase
      A. In solution, the enzyme is bright yellow. It is a dimer of subunits (34 kDa)
      that contain one molecule of flavin mononucleotide each. The enzyme shows optimal
      function in the pH range 7.5-9.0. It is specific for L-dihydroorotate as
      substrate and can use dichlorophenolindophenol, potassium hexacyanoferrate (III),
      and, to a lower extent, also molecular oxygen as acceptors of the reducing
      equivalents, whereas the pyridine nucleotide coenzymes (NAD+, NADP+) and the
      respiratory quinones (i.e., vitamins Q6, Q10 and K2) were inactive. The enzyme
      has been crystallized from solutions of 30% polyethylene glycol, 0.2 M sodium
      acetate, and 0.1 M Tris-HCl, pH 8.5. The resulting yellow crystals diffracted
      well and showed little sign of radiation damage during diffraction experiments.
      The crystals are monoclinic, space group P21 with unit cell dimensions a = 54.19
      A, b = 109.23 A, c = 67.17 A, and beta = 104.5 degrees. A native data set has
      been collected with a completeness of 99.3% to 2.0 A and an Rsym value of 5.2%.
      Analysis of the solvent content and the self-rotation function indicates that the
      two subunits in the asymmetric unit are related by a noncrystallographic twofold
      axis perpendicular to the crystallographic b and c axes.

PMID- 8732755
TI  - Structural investigation of the alpha-1-antichymotrypsin: prostate-specific
      antigen complex by comparative model building.
AB  - Prostate-specific antigen (PSA), produced by prostate cells, provides an
      excellent serum marker for prostate cancer. It belongs to the human kallikrein
      family of enzymes, a second prostate-derived member of which is human glandular
      kallikrein-1 (hK2). Active PSA and hK2 are both 237-residue kallikrein-like
      proteases, based on sequence homology. An hK2 model structure based on the serine
      protease fold is presented and compared to PSA and six other serine proteases in
      order to analyze in depth the role of the surface-accessible loops surrounding
      the active site. The results show that PSA and hK2 share extensive structural
      similarity and that most amino acid replacements are centered on the loops
      surrounding the active site. Furthermore, the electrostatic potential surfaces
      are very similar for PSA and hK2. PSA interacts with at least two serine protease
      inhibitors (serpins): alpha-1-antichymotrypsin (ACT) and protein C inhibitor
      (PCI). Three-dimensional model structures of the uncleaved ACT molecule were
      developed based upon the recent X-ray structure of uncleaved antithrombin. The
      serpin was docked both to PSA and hK2. Amino acid replacements and electrostatic
      complementarities indicate that the overall orientation of the proteins in these
      complexes is reasonable. In order to investigate PSA's heparin interaction sites,
      electrostatic computations were carried out on PSA, hK2, protein C, ACT, and PCI.
      Two heparin binding sites are suggested on the PSA surface and could explain the
      enhanced complex formation between PSA and PCI, while inhibiting the formation of
      the ACT-PSA complex, PSA, hK2, and their preliminary complexes with ACT should
      facilitate the understanding and prediction of structural and functional
      properties for these important proteins also with respect to prostate diseases.

PMID- 8732757
TI  - The structural homology between uteroglobin and the pore-forming domain of
      colicin A suggests a possible mechanism of action for uteroglobin.
AB  - Although the exact physiological function of uteroglobin is not known, it has
      been suggested that it may function by inhibiting phospholipase A2. We have found
      that the uteroglobin fold is embedded in that of the poreforming domain of
      colicin A. Colicin A is an antibiotic protein that kills sensitive Escherichia
      coli cells by forming a pore in their phospholipid membrane. The RMS deviation
      between the C alpha atoms after the structural alignment is 2.39 A for the 52
      superimposed residues. In the alignment, uteroglobin helices 1, 2, 3, and 4 align
      with colicin A helices 6, 7, 3, and 4, respectively. The motif is strongly
      amphipathic in both proteins. On the basis of this common structural motif and of
      known experimental data on both proteins, we propose that UG binds to the
      membrane surface by lying on it monotopically. The phospholipase A2 inhibition
      would follow this initial binding step.

PMID- 8732758
TI  - Extremely thermostable L(+)-lactate dehydrogenase from Thermotoga maritima:
      cloning, characterization, and crystallization of the recombinant enzyme in its
      tetrameric and octameric state.
AB  - L(+)-lactate dehydrogenase (LDH; E.C.1.1.1.27) from the hyperthermophilic
      bacterium Thermotoga maritima has been shown to represent the most stable LDH
      isolated so far (Wrba A, Jaenicke R, Huber R, Stetter KO, 1990, Eur J Biochem
      188:195-201). In order to obtain the enzyme in amounts sufficient for physical
      characterization, and to analyze the molecular basis of its intrinsic stability,
      the gene was cloned and expressed functionally in Escherichia coli. Growth of the
      cells and purification of the enzyme were performed aerobically at 26 degrees C,
      i.e., ca. 60 degrees below the optimal growth temperature of Thermotoga. Two
      enzyme species with LDH activity were purified to homogeneity. Crystals of the
      enzyme obtained at 4 degrees C show satisfactory diffraction suitable for X-ray
      analysis up to a resolution of 2.8 A. As shown by gel-permeation chromatography,
      chemical crosslinking, light scattering, analytical ultracentrifugation, and
      electron microscopy, the two LDH species represent homotetramers and homooctamers
      (i.e., dimers of tetramers), with a common subunit molecular mass of 35 kDa. The
      spectroscopic characteristics (UV absorption, fluorescence emission, near- and
      far-UV CD) of the two species are indistinguishable. The calculated alpha-helix
      content is 45%, in accordance with the result of homology modeling. Compared to
      the tetrameric enzyme, the octamer exhibits reduced specific activity, whereas KM
      is unalatered. The extreme intrinsic stability of the protein is reflected by its
      unaltered catalytic activity over 4 h at 85 degrees C; irreversible thermal
      denaturation becomes significant at approximately 95 degrees C. The anomalous
      resistance toward chemical denaturation using guanidinium chloride and urea
      confirms this observation. Both the high optimal temperature and the pH optimum
      of the catalytic activity correspond to the growth conditions of T. maritima in
      its natural habitat.

PMID- 8732759
TI  - Interaction of subtilisins with serpins.
AB  - Serpins are well-characterized inhibitors of the chymotrypsin family serine
      proteinases. We have investigated the interaction of two serpins with members of
      the subtilisin family, proteinases that possess a similar catalytic mechanism to
      the chymotrypsins, but a totally different scaffold. We demonstrate that alpha 1
      proteinase inhibitor inhibits subtilisin Carlsberg and proteinase K, and alpha 1
      antichymotrypsin inhibits proteinase K, but not subtilisin Carlsberg. When
      inhibition occurs, the rate of formation and stability of the complexes are
      similar to those formed between serpins and chymotrypsin family members. However,
      inhibition of subtilisins is characterized by large partition ratios where more
      than four molecules of each serpin are required to inhibit one subtilisin
      molecule. The partition ratio is caused by the serpins acting as substrates or
      inhibitors. The ratio decreases as temperature is elevated in the range 0-45
      degrees C, indicating that the serpins are more efficient inhibitors at high
      temperature. These aspects of the subtilisin interaction are all observed during
      inhibition of chymotrypsin family members by serpins, indicating that serpins
      accomplish inhibition of these two distinct proteinase families by the same
      mechanism.

PMID- 8732760
TI  - 2D 1H and 3D 1H-15N NMR of zinc-rubredoxins: contributions of the beta-sheet to
      thermostability.
AB  - Based on 2D 1H-1H and 2D and 3D 1H-15N NMR spectroscopies, complete 1H NMR
      assignments are reported for zinc-containing Clostridium pasteurianum rubredoxin
      (Cp ZnRd). Complete 1H NMR assignments are also reported for a mutated Cp ZnRd,
      in which residues near the N-terminus, namely, Met 1, Lys 2, and Pro 15, have
      been changed to their counterparts, (-), Ala and Glu, respectively, in rubredoxin
      from the hyperthermophilic archaeon, Pyrococcus furiosus (Pf Rd). The secondary
      structure of both wild-type and mutated Cp ZnRds, as determined by NMR methods,
      is essentially the same. However, the NMR data indicate an extension of the three
      stranded beta-sheet in the mutated Cp ZnRd to include the N-terminal Ala residue
      and Glu 15, as occurs in Pf Rd. The mutated Cp Rd also shows more intense NOE
      cross peaks, indicating stronger interactions between the strands of the beta
      sheet and, in fact, throughout the mutated Rd. However, these stronger
      interactions do not lead to any significant increase in thermostability, and both
      the mutated and wild-type Cp Rds are much less thermostable than Pf Rd. These
      correlations strongly suggest that, contrary to a previous proposal [Blake PR et
      al., 1992, Protein Sci 1:1508-1521], the thermostabilization mechanism of Pf Rd
      is not dominated by a unique set of hydrogen bonds or electrostatic interactions
      involving the N-terminal strand of the beta-sheet. The NMR results also suggest
      that an overall tighter protein structure does not necessarily lead to increased
      thermostability.

PMID- 8732761
TI  - Protein design automation.
AB  - We have conceived and implemented a cyclical protein design strategy that couples
      theory, computation, and experimental testing. The combinatorially large number
      of possible sequences and the incomplete understanding of the factors that
      control protein structure are the primary obstacles in protein design. Our
      protein design automation algorithm objectively predicts protein sequences likely
      to achieve a desired fold. Using a rotamer description of the side chains, we
      implemented a fast discrete search algorithm based on the Dead-End Elimination
      Theorem to rapidly find the globally optimal sequence in its optimal geometry
      from the vast number of possible solutions. Rotamer sequences were scored for
      steric complementarity using a van der Waals potential. A Monte Carlo search was
      then executed, starting at the optimal sequence, in order to find other high
      scoring sequences. As a test of the design methodology, high-scoring sequences
      were found for the buried hydrophobic residues of a homodimeric coiled coil based
      on GCN4-p1. The corresponding peptides were synthesized and characterized by CD
      spectroscopy and size-exclusion chromatography. All peptides were dimeric and
      nearly 100% helical at 1 degree C, with melting temperatures ranging from 24
      degrees C to 57 degrees C. A quantitative structure activity relation analysis
      was performed on the designed peptides, and a significant correlation was found
      with surface area burial. Incorporation of a buried surface area potential in the
      scoring of sequences greatly improved the correlation between predicted and
      measured stabilities and demonstrated experimental feedback in a complete design
      cycle.

PMID- 8732762
TI  - Enzymatic and fluorescence studies of four single-tryptophan mutants of rat
      testis fructose 6-phosphate,2-kinase:fructose 2,6-bisphosphatase.
AB  - In order to determine environments around four tryptophan residues, located in
      the N-terminus, in the kinase and in the phosphatase domains of rat testis Fru 6
      P,2-kinase:Fru 2,6-bisphosphatase, mutant enzymes containing a single tryptophan
      were constructed by site-directed mutagenesis. The kinetic constants of these
      mutant enzymes were similar to those of the wild-type enzyme. The sum of the
      fluorescence intensities of the enzymes was 1.5 x that of the wild-type enzyme,
      and Trp 299, Trp 64, Trp 15, and Trp 320 contributed 38%, 28%, 17%, and 17%,
      respectively. The fluorescence polarization of the wild-type enzyme was
      significantly lower than any of the mutant enzymes, suggesting proximity of two
      tryptophan residues in the wild-type enzyme. The polarization in the presence of
      Fru 6-P affected only Trp 15, which suggested that it is located near the Fru 6-P
      binding site, but Trp 64 is not. Inactivation of both enzyme activities and
      unfolding of these enzymes in guanidine were monitored by activity assays and
      fluorescence intensities and maxima. Both Fru 6-P,2-kinase and Fru 2,6
      bisphosphatase activities of all these enzymes were inactivated between 0.7 and 1
      M guanidine. Enzymes containing Trp 64 or Trp 15 showed biphasic fractional
      unfolding curves, but those of Trp 299 or Trp 320 showed gradual steady changes.
      Fluorescence quenching by iodide indicated that Trp 64 was not accessible and
      that other Trp residues were only slightly accessible to solvent. These results
      suggest that all the Trp residues are in heterogeneous environments and that none
      are exposed on the protein surface.

PMID- 8732764
TI  - Energetics of structural domains in alpha-lactalbumin.
AB  - alpha-Lactalbumin is a small, globular protein that is stabilized by four
      disulfide bonds and contains two structural domains. One of these domains is rich
      in alpha-helix (the alpha-domain) and has Cys 6-Cys 120 and Cys 28-Cys 111
      disulfide bonds. The other domain is rich in beta-sheet (the beta-domain), has
      Cys 61-Cys 77 and Cys 73-Cys 91 disulfide bonds, and includes one calcium binding
      site. To investigate the interaction between domains, we studied derivatives of
      bovine alpha-lactalbumin differing in the number of disulfide bonds, using
      calorimetry and CD at different temperatures and solvent conditions. The three
      disulfide form, having a reduced Cys 6-Cys 120 disulfide bond with
      carboxymethylated cysteines, is similar to intact alpha-lactalbumin in secondary
      and tertiary structure as judged by its ellipticity in the near and far UV. the
      two-disulfide form of alpha-lactalbumin, having reduced Cys 6-Cys 120 and Cys 28
      Cys 111 disulfide bonds with carboxymethylated cysteines, retains about half the
      secondary and tertiary structure of the intact alpha-lactalbumin. The remaining
      structure is able to bind calcium and unfolds cooperatively upon heating,
      although at lower temperature and with significantly lower enthalpy and entropy.
      We conclude that, in the two disulfide form, alpha-lactalbumin retains its
      calcium-binding beta-domain, whereas the alpha-domain is unfolded. It appears
      that the beta-domain does not require alpha-domain to fold, but its structure is
      stabilized significantly by the presence of the adjacent folded alpha-domain.

PMID- 8732763
TI  - A novel family of phospholipase D homologues that includes phospholipid synthases
      and putative endonucleases: identification of duplicated repeats and potential
      active site residues.
AB  - Phosphatidylcholine-specific phospholipase D (PLD) enzymes catalyze hydrolysis of
      phospholipid phosphodiester bonds, and also transphosphatidylation of
      phospholipids to acceptor alcohols. Bacterial and plant PLD enzymes have not been
      shown previously to be homologues or to be homologous to any other protein. Here
      we show, using sequence analysis methods, that bacterial and plant PLDs show
      significant sequence similarities both to each other, and to two other classes of
      phospholipid-specific enzymes, bacterial cardiolipin synthases, and eukaryotic
      and bacterial phosphatidylserine synthases, indicating that these enzymes form an
      homologous family. This family is suggested also to include two Poxviridae
      proteins of unknown function (p37K and protein K4), a bacterial endonuclease
      (nuc), an Escherichia coli putative protein (o338) containing an N-terminal
      domain showing similarities with helicase motifs V and VI, and a Synechocystis
      sp. putative protein with a C-terminal domain likely to possess a DNA-binding
      function. Surprisingly, four regions of sequence similarity that occur once in
      nuc and o338, appear twice in all other homologues, indicating that the latter
      molecules are bi-lobed, having evolved from an ancestor or ancestors that
      underwent a gene duplication and fusion event. It is suggested that, for each of
      these enzymes, conserved histidine, lysine, aspartic acid, and/or asparagine
      residues may be involved in a two-step ping pong mechanism involving an enzyme
      substrate intermediate.

PMID- 8732765
TI  - Pi-turns in proteins and peptides: Classification, conformation, occurrence,
      hydration and sequence.
AB  - The i + 5-->i hydrogen bonded turn conformation (pi-turn) with the fifth residue
      adopting alpha L conformation is frequently found at the C-terminus of helices in
      proteins and hence is speculated to be a "helix termination signal." An analysis
      of the occurrence of i + 5-->i hydrogen bonded turn conformation at any general
      position in proteins (not specifically at the helix C-terminus), using
      coordinates of 228 protein crystal structures determined by X-ray crystallography
      to better than 2.5 A resolution is reported in this paper. Of 486 detected pi
      turn conformations, 367 have the (i + 4)th residue in alpha L conformation,
      generally occurring at the C-terminus of alpha-helices, consistent with previous
      observations. However, a significant number (111) of pi-turn conformations occur
      with (i + 4)th residue in alpha R conformation also, generally occurring in alpha
      helices as distortions either at the terminii or at the middle, a novel finding.
      These two sets of pi-turn conformations are referred to by the names pi alpha L
      and pi alpha R-turns, respectively, depending upon whether the (i + 4)th residue
      adopts alpha L or alpha R conformations. Four pi-turns, named pi alpha L'-turns,
      were noticed to be mirror images of pi alpha L-turns, and four more pi-turns,
      which have the (i + 4)th residue in beta conformation and denoted as pi beta
      turns, occur as a part of hairpin bend connecting twisted beta-strands.
      Consecutive pi-turns occur, but only with pi alpha R-turns. The preference for
      amino acid residues is different in pi alpha L and pi alpha R-turns. However,
      both show a preference for Pro after the C-termini. Hydrophilic residues are
      preferred at positions i + 1, i + 2, and i + 3 of pi alpha L-turns, whereas
      positions i and i + 5 prefer hydrophobic residues. Residue i + 4 in pi alpha L
      turns is mainly Gly and less often Asn. Although pi alpha R-turns generally occur
      as distortions in helices, their amino acid preference is different from that of
      helices. Poor helix formers, such as His, Tyr, and Asn, also were found to be
      preferred for pi alpha R-turns, whereas good helix former Ala is not preferred.
      pi-Turns in peptides provide a picture of the pi-turn at atomic resolution. Only
      nine peptide-based pi-turns are reported so far, and all of them belong to pi
      alpha L-turn type with an achiral residue in position i + 4. The results are of
      importance for structure prediction, modeling, and de novo design of proteins.

PMID- 8732766
TI  - Protein fold recognition using sequence-derived predictions.
AB  - In protein fold recognition, one assigns a probe amino acid sequence of unknown
      structure to one of a library of target 3D structures. Correct assignment depends
      on effective scoring of the probe sequence for its compatibility with each of the
      target structures. Here we show that, in addition to the amino acid sequence of
      the probe, sequence-derived properties of the probe sequence (such as the
      predicted secondary structure) are useful in fold assignment. The additional
      measure of compatibility between probe and target is the level of agreement
      between the predicted secondary structure of the probe and the known secondary
      structure of the target fold. That is, we recommend a sequence-structure
      compatibility function that combines previously developed compatibility functions
      (such as the 3D-1D scores of Bowie et al. [1991] or sequence-sequence replacement
      tables) with the predicted secondary structure of the probe sequence. The effect
      on fold assignment of adding predicted secondary structure is evaluated here by
      using a benchmark set of proteins (Fischer et al., 1996a). The 3D structures of
      the probe sequences of the benchmark are actually known, but are ignored by our
      method. The results show that the inclusion of the predicted secondary structure
      improves fold assignment by about 25%. The results also show that, if the true
      secondary structure of the probe were known, correct fold assignment would
      increase by an additional 8-32%. We conclude that incorporating sequence-derived
      predictions significantly improves assignment of sequences to known 3D folds.
      Finally, we apply the new method to assign folds to sequences in the SWISSPROT
      database; six fold assignments are given that are not detectable by standard
      sequence-sequence comparison methods; for two of these, the fold is known from X
      ray crystallography and the fold assignment is correct.

PMID- 8732767
TI  - Chimeric hemoglobins--hybrids of human and swine hemoglobin: assembly and
      stability of interspecies hybrids.
AB  - Transgenic swine expressing human HbA contained only one of two types of the
      anticipated interspecies hybrids, namely H alpha 2 P beta 2 (H = human, P =
      swine). In an attempt to establish whether the absence of the swine alpha and
      human beta (P alpha 2 H beta 2) hybrid in vivo is a reflection of the lack of
      complementarity between the interspecies chains to generate appropriate
      interfaces, we have undertaken the in vitro assembly of swine alpha and human
      beta chimeric tetramer. In contrast to the in vivo transgenic swine system, in
      vitro the hybrid of swine alpha human beta chain is assembled readily and the
      hybrid exhibits normal cooperative oxygen binding. Both the swine alpha human
      beta and the human alpha swine beta interspecies hybrids are stable around
      neutral pH and do not segregate into parent tetramers even when mixed together.
      On the other hand, nearly complete exchange of P alpha chain of P alpha 2 H beta
      2 hybrid occurs in the presence of H alpha chain at pH 6.0 and room temperature,
      resulting in the formation of HbA. However, very little of such an exchange
      reaction takes place at pH 7.0. These results suggest that the thermodynamic
      stability of P alpha 2 H beta 2 hybrid is lower compared to that of HbA. In
      contrast, P beta chain of H alpha 2 P beta 2 hybrid is refractory to exchange
      with H beta chain at pH 7.0 as well as at pH 6.0, suggesting that the stability
      of H alpha 2 P beta 2 is higher compared to that of HbA (H alpha 2 H beta 2). The
      swine alpha human beta chimeric Hb undergoes subunit exchange reaction with human
      alpha-chain in the presence of 0.9 M MgCl2, at pH 7.0. This demonstrates the
      lower thermodynamic stability of the intradimeric interactions of the heterodimer
      even at neutral pH. A synergistic coupling of the intra- and interdimeric
      interactions of the swine alpha and human beta chain heterodimer is essential for
      the thermodynamic stability of the chimeric Hb under the physiological
      conditions. Accordingly, we speculate that the lower thermodynamic stability of P
      alpha H beta heterodimer (compared to the homodimers H alpha H beta and P alpha P
      beta) facilitates its segregation into the homodimers by subunit exchange
      reaction involving either H alpha or P beta. This molecular aspect by itself or
      possibly along with other cellular aspects of the swine system results in the
      absence of P alpha 2 H beta 2 hybrid in transgenic swine expressing HbA.

PMID- 8732768
TI  - Preliminary crystallographic studies of an anti-HIV-1 protease antibody that
      inhibits enzyme activity.
AB  - F11.2.32, a monoclonal antibody directed against the HIV-1 protease, displays
      strong inhibitory effects toward the catalytic activity of the enzyme. The
      antibody cross-reacts with peptides 36-46 and 36-57 from the protease. Crystals
      of the Fab have been obtained both in the free state and as complexes formed with
      the protease peptide fragments, 36-46 and 36-57. Diffraction data have been
      collected for the free and complexed forms of Fab F11.2.32 and preliminary models
      for the crystal structures were obtained by molecular replacement.

PMID- 8732769
TI  - 1H and 15N nuclear magnetic resonance assignment and secondary structure of the
      cytotoxic ribonuclease alpha-Sarcin.
AB  - The ribosome-inactivating protein alpha-Sarcin (alpha S) is a 150-residue fungal
      ribonuclease that, after entering sensitive cells, selectively cleaves a single
      phosphodiester bond in an universally conserved sequence of the major rRNA to
      inactivate the ribosome and thus exert its cytotoxic action. As a first step
      toward establishing the structure-dynamics-function relationships in this system,
      we have carried out the assignment of the 1H and 15N NMR spectrum of alpha S on
      the basis of homonuclear (1H-1H) and heteronuclear (1H-15N) two-dimensional
      correlation spectra of a uniformly 15N-labeled sample, and two selectively 15N
      labeled (Tyr and Phe) samples, as well as a single three-dimensional experiment.
      The secondary structure of alpha S, as derived from the characteristic patterns
      of dipolar connectivities between backbone protons, conformational chemical
      shifts, and the protection of backbone amide protons against exchange, consists
      of a long N-terminal beta-hairpin, a short alpha-helical segment, and a C
      terminal beta-sheet of five short strands arranged in a + 1, + 1, + 1, + 1
      topology, connected by long loops in which the 13 Pro residues are located.

PMID- 8732770
TI  - Crystals of the neurotrophins.
AB  - The neurotrophins show a high degree of amino acid sequence homology, share
      similar solution properties, and display distinct but parallel functionalities.
      Here we report the crystallization and preliminary X-ray characterization of
      three neurotrophins: brain-derived neurotrophin, neurotrophin 3, and the
      heterodimer between brain-derived neurotrophin and neurotrophin 4. These findings
      are related to other published crystal parameters for neurotrophins, leading to
      the observation that, although crystal packing is highly variant, neurotrophins
      share common solubilities with respect to crystal growth.

PMID- 8732771
TI  - Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and
      atherogenesis.
AB  - Although it has been known for over 50 years that lipoprotein lipase (LPL)
      hydrolyzes triglyceride in chylomicrons, during the past half decade there has
      been a reinterest in the physiologic and pathophysiologic actions of this enzyme.
      In part, this has coincided with clinical studies implicating increased
      postprandial lipemia as a risk factor for atherosclerosis development. In
      addition, the recent creation of genetically altered mice with
      hypertriglyceridemia has focused the interest of geneticists and physiologists on
      the pathophysiology of triglyceride metabolism. As reviewed in this article, it
      is apparent that the lipolysis reaction is only partially understood. Several
      factors other than LPL are critical modulators of this process, in part, because
      the reaction requires the lipoproteins to interact with the arterial or capillary
      wall. Among the factors that affect this are the apolipoprotein composition of
      the particles, the size of the lipoproteins, and how LPL is displayed along the
      endothelial luminal surface. Zilversmit's observation that LPL activity is found
      in greater amounts in atherosclerotic than normal arteries has led to a large
      number of experiments linking LPL with atherogenesis. In medium and large
      arteries LPL is found on the luminal endothelial surface and in macrophage-rich
      areas within the plaque. LPL actions in both of these locations probably have
      major effects on the biology of the blood vessel. Possible atherogenic actions
      for this LPL based on in vitro experiments are reviewed.

PMID- 8732772
TI  - The usefulness of dietary medium-chain triglycerides in body weight control: fact
      or fancy?
AB  - Compared to long-chain triglycerides (LCT), medium-chain triglycerides (MCT)
      display some specific physico-chemical, and biological characteristics. Thus, MCT
      are currently used in clinical nutrition as energy-yielding substrates, and have
      been advocated for three decades as a useful mean for body weight reduction. This
      review encompasses most aspects of MCT metabolism arguing this slimming
      hypothesis pro and con. Findings in support of the opinion (lower energy density,
      control of satiety, rapid intrahepatic delivery and oxidation rates, poor adipose
      tissue incorporation) may be invalidated by counteracting data (stimulation of
      insulin secretion and of anabolic-related processes, increased de novo fatty acid
      synthesis, induced hypertriglyceridemia). The balance between these two opposing
      influences depends on the composition (energy intake, nature of ingredients,
      MCT/LCT ratio, octanoate/decanoate ratio) and duration of the regimen. Due to the
      high energy level (around 50%) of MCT necessary to achieve body weight loss, long
      term compliance to such slimming regimens is unlikely in human nutrition.

PMID- 8732773
TI  - Heterozygosity for Asn291-->Ser mutation in the lipoprotein lipase gene in two
      Finnish pedigrees: effect of hyperinsulinemia on the expression of
      hypertriglyceridemia.
AB  - We describe two Finnish kindreds with the Asn291 --> Ser mutation (A291S) of the
      lipoprotein lipase (LPL) gene. Sixteen subjects (9 male, 7 female) heterozygous
      for this mutation were studied and compared with 17 unaffected family members or
      spouses (family controls) and 19 unrelated healthy subjects (population
      controls). In the group of subjects heterozygous for the A291S mutation,
      postheparin plasma LPL activity was on average 23% lower than in the family
      controls and 29% lower than in the population controls. In agreement, in vitro
      expression studies with COS-7 cells showed that the mutant protein exhibits
      approximately 50% of the lipolytic activity of the wild-type protein. Median
      serum triglyceride concentration was 2.90 mmol/l in the group of heterozygotes,
      compared with 1.14 mmol/l in the family controls (P < 0.01) and 0.99 mmol/l in
      the population controls (P < 0.001). The heterozygotes also had a marked
      preponderance of small dense low density lipoproteins (LDL) as assessed by
      gradient gel electrophoresis. Nine of the heterozygous subjects were
      hypertriglyceridemic (serum triglyceride concentration > 2.0 mmol/l). Age or body
      mass index were not related to the presence of hypertriglyceridemia. By contrast,
      all hypertriglyceridemic subjects were either hyperinsulinemic (serum insulin
      concentration > 10 mU/l, n = 7) or had diabetes (n = 2). In a multivariate
      regression analysis, very low density lipoprotein (VLDL) triglyceride level was
      significantly and independently related to serum apolipoprotein B concentration,
      the presence of the A291S mutation, serum insulin concentration, and postheparin
      plasma LPL activity. The Asn291-->Ser mutation of the LPL gene results in reduced
      lipolytic activity. However, dyslipidemia appears to manifest only if VLDL
      production is also increased. Hyperinsulinemia was the major determinant of
      excessive VLDL synthesis and dyslipidemia among the subjects heterozygous for the
      A291S mutation in this study.

PMID- 8732774
TI  - Irreversible inhibition of hepatic fatty acid salt uptake by photoaffinity
      labeling with 11, 11-azistearate.
AB  - In order to have a model compound for detection of proteins involved in transport
      and metabolism of long-chain fatty acid salts by photoaffinity labeling 11,11
      azistearate and 11,11-azi[G-3H]stearate (specific radioactivity 2.78 TBq/mmol)
      were synthesized. The suitability of 11,11-azi[G-3H]stearate for photoaffinity
      labeling was demonstrated by incorporation into BSA (bovine serum albumin) and H
      FABP (hepatic fatty acid salt-binding protein) of rat liver. Repeated
      photoaffinity labeling resulted in a clear decrease of the binding capacities of
      both proteins. Labeling of protein mixtures with 11,11-azi[G-3H]stearate showed
      that binding proteins for long-chain fatty acid salts interact specifically with
      this probe. Photoaffinity labeling of isolated hepatocytes using 300 microM 11,11
      azistearate in the presence of 100 microM BSA resulted in the irreversible
      inhibition of the uptake of stearate and its analogue 2,2,3,3,18,18,18
      heptafluorostearate nearly to the same extent of about 30%. Irreversible
      inhibition of the uptake of long-chain fatty acid salts by photoaffinity labeling
      did not alter the mediated transport of cholyltaurine and has no effect on the
      uptake of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol, a compound that
      crosses the hepatocyte membrane by simple diffusion. The irreversible inhibition
      of membrane transport by photoaffinity labeling demonstrates the existence of a
      specific transport system for the uptake of long-chain fatty acid salts into
      hepatocytes.

PMID- 8732775
TI  - Lipoprotein lipase-enhanced binding of human triglyceride-rich lipoproteins to
      heparan sulfate: modulation by apolipoprotein E and apolipoprotein C.
AB  - The objective of this study was to investigate whether compositional variation in
      apolipoprotein (apo) content of triglyceride-rich lipoproteins (TRLP) modulates
      binding of heparan sulfate proteoglycans (HSPG). Human TRLP was enriched with
      apoE and apoCs and the ability to bind biotin-conjugated heparan sulfate (b-HS)
      was studied in the presence or absence of heat-inactivated lipoprotein lipase
      (LPL). TRLP, associated with LPL, showed an increased capacity to bind b-HS
      compared with TRLP alone. Low density lipoproteins (LDL) bound both b-HS and LPL
      with a higher affinity than TRLP. ApoE enrichment of TRLP resulted in an enhanced
      binding of b-HS. Increased binding of b-HS to TRLP by the combination of apoE
      enrichment and LPL addition was found to be complementary, not affecting their
      individual binding capacity. TRLP enrichment with apoC led to the formation of an
      apoC-rich, apoE-poor particle; this alteration by itself did not change the
      ability to bind b-HS. ApoC enrichment of TRLP resulted in a reduced capacity to
      bind LPL and therefore a subsequently reduced capacity to bind b-HS, compared
      with control TRLP associated with LPL. Competition studies revealed that b-HS
      binding to TRLP was fully displaceable by lactoferrin but barely by heparan
      sulfate, dermatan sulfate, or chondroitin-4-sulfate. Using TRLP coated to
      microtiter wells and associated with LPL, the b-HS displacement patterns were
      comparable to those obtained with coated LDL in the presence or absence of LPL.
      The cell-free system that was used enabled us to identify the functions of apoC
      and apoE in the binding of TRLP to LPL and HSPG. Both LPL and apoE increased the
      ability of TRLP to bind HSPG. The apoC content of TRLP regulated the docking of
      TRLP to LPL. ApoC enrichment reduced the affinity or capacity of TRLP to LPL
      binding, and this has relevance for the lipolytic cascade.

PMID- 8732776
TI  - Monoacylglycerols alter the lipid composition and molecular mobility of
      phosphatidylcholine bilayers: 13C NMR evidence of dynamic lipid remodeling.
AB  - The physical effects of monoacylglycerols (MAG) in small unilamellar vesicles
      composed of phosphatidyl-choline (PC), triolein, cholesterol, and varying amounts
      of monopalmitin and monoolein were studied by 13C-NMR. The signal to noise ratio
      of the carbonyls of PC and triolein were enhanced by the addition of 1,2-di-[1
      13C]palmitoylphosphatidylcholine and tri-[1-13C]oleoylglycerol. The linewidths of
      the carbonyl-13C, choline methyl, olefinic carbon, and terminal methyl resonances
      were measured digitally from vesicles with 0 to 42 mol % of MAG. Significant
      increases in the linewidth of carbonyl (P < 0.05), olefinic and terminal methyl
      carbons (P < 0.01) of vesicles containing 42 mol % monopalmitin indicated that
      these groups experienced restricted molecular mobility at high monopalmitin
      concentrations. However, more striking was the apparent displacement of triolein
      from the surface environment of PC bilayers to an oil-like environment in systems
      containing only 8 mol % monopalmitin. Displacement of triolein from the surface
      by monoolein occurred only above 15 mol %. Thus, saturated and monounsaturated
      monoacylglycerols, natural products of lipoprotein metabolism, dynamically alter
      both the lipid composition and molecular mobility of lipoprotein surfaces in
      distinct ways.

PMID- 8732777
TI  - Incorporation of medium chain triacylglycerols into phospholipid bilayers: effect
      of long chain triacylglycerols, cholesterol, and cholesteryl esters.
AB  - The ability of water-insoluble molecules such as triacylglycerols to partition
      from oil phases into phospholipid interfaces may be crucial to their hydrolysis
      by lipases in the aqueous environment of plasma and cells. This study uses high
      resolution and magic angle spinning 13C NMR spectros-copy to measure the
      solubility of the 8-carbon medium chain triacylglycerol, trioctanoin, in the
      lamellar structure of phospholipids (vesicles and multilayers) in the presence of
      other neutral lipids that may compete for an interfacial location (long chain
      triacylglycerol, cholesteryl ester, and cholesterol). In the presence of a
      saturating concentration of triolein (approximately 3 mole%), the solubility of
      trioctanoin in egg phosphatidylcholine vesicles decreased from 10 mole% to 7
      mole%. The presence of a saturating concentration of trioctanoin (approximately
      10 mole%) decreased the interfacial solubility of long chain triolein to
      approximately 1 mole%. Cholesteryl oleate in phospholipid vesicles slightly
      diminished the incorporation of trioctanoin into the surface. The presence of
      cholesterol reduced the interfacial solubility of trioctanoin, but at a high
      level of cholesterol (30 mole%), trioctanoin had a solubility of 3 mole%. Thus,
      even in the presence of other competing neutral lipids, medium chain
      triacylglycerol retains a favorable location and surface concentration for
      efficient hydrolysis. 13C NMR analysis thus provides an explanation for
      preferential hydrolysis of medium, compared to long chain triacylglycerol, in a
      physical blend of medium and long chain triacylglycerol in a single emulsion
      particle, and in general, a valuable approach to determine substrate availability
      at phospholipid surfaces.

PMID- 8732778
TI  - Hypoxia attenuates metabolism of platelet activating factor by fetal and newborn
      lamb lungs.
AB  - The metabolism of platelet activating factor (PAF) by lungs of near-term fetal
      and 5- to 9-day-old lambs was studied during normoxia and hypoxia at 37 degrees C
      in 30 mM Tris buffer. PAF synthesis was studied in lung cytosol and membrane
      using 250 microM [3H]acetyl CoA, 40 microM lyso-PAF, and 50 micrograms protein.
      PAF catabolism was studied in lung homogenate (LH) using 50 microM [3H]alkyl-PAF.
      PAF was extracted and assayed by thin-layer chromatography (TLC) and liquid
      scintillation spectrometry. Levels of PAF synthesized (nmol/min per mg protein)
      by fetal lung membrane versus cytosol were 1.35 +/- 0.07 versus 0.61 +/- 0.08,
      which were greater than those by newborn which were 0.33 +/- 0.07 versus 0.17 +/-
      0.03. Hypoxia did not alter PAF synthesis by the lungs. PAF catabolism (nmol lyso
      PAF/min per mg protein) by fetal LH was 0.07 +/- 0.01, which increased to 0.24 +/
      0.02 during normoxia. In newborn LH, the rate was 0.24 +/- 0.04 and increased to
      0.33 +/- 0.01 during normoxia. PAF catabolism was higher in newborn than in fetal
      LH. An increase in pO2 augmented PAF catabolism, more in fetal than in newborn
      LH. Thus rate of PAF synthesis decreases from fetus to newborn, but PAF
      catabolism increases from fetus to newborn. The higher rate of PAF synthesis
      coupled with a low rate of PAF catabolism in the hypoxic environment of fetal
      lungs may predispose the fetus to a high PAF level, which may contribute to the
      high basal vasomotor tone in fetal lungs. A fall in PAF level with oxygenation,
      due to increased PAF catabolism, may facilitate the normal fall in pulmonary
      vascular resistance at birth.

PMID- 8732779
TI  - Roles of different hydrophobic constituents in the adsorption of pulmonary
      surfactant.
AB  - Surface tension-time adsorption isotherms were measured at 37 degrees C for calf
      lung surfactant extract (CLSE) and subfractions of its constituents: the complete
      mix of surfactant phospholipids (PPL), phospholipids depleted in anionic
      phospholipids (mPPL), hydrophobic surfactant proteins plus phospholipids (SP&PL,
      SP&mPL), and neutral lipids plus phospholipids (N&PL). Adsorption experiments
      were done using a static bubble surfactometer where diffusion resistance was
      present, and in a Teflon dish where diffusion was minimized by subphase stirring.
      The contribution of diffusion to bubble adsorption measurements decreased as
      phospholipid concentration increased, and was small at 0.25 mM phospholipid. At
      this phospholipid concentration, PPL, mPPL, and N&PL all adsorbed more rapidly
      and to lower final surface tensions than dipalmitoyl phosphatidylcholine (DPPC)
      on the bubble. However, none of these phospholipid mixtures adsorbed to surface
      tensions below 46 mN/m after 20 min, behavior that was significantly worse than
      CLSE, SP&PL, and SP&mPL which additionally contained hydrophobic SP. Both CLSE
      and SP&PL rapidly adsorbed to surface tensions below 25 mN/m at 0.25 mM
      phospholipid concentration on the bubble, as did SP&mPL at a somewhat reduced
      rate. Further experiments defining the influence of hydrophobic protein content
      showed that addition of even 0.13% SP (by wt) to PPL improved adsorption
      substantially, and that mixtures of PPL combined with 1% SP had adsorption very
      similar to CLSE. Mixtures of SP combined with mPPL had faster adsorption than
      corresponding mixtures of SP:DPPC, and neither fully matched the adsorption rates
      of CLSE and SP&PL even at high SP levels (4% in SP:mPPL and 5.2% in SP:DPPC).
      These results demonstrate that although the secondary zwitterionic and anionic
      phospholipids and neutral lipids in lung surfactant enhance adsorption relative
      to DPPC, the hydrophobic SP have a much more pronounced effect in promoting the
      rapid entry of pulmonary surfactant into the air-water interface.

PMID- 8732780
TI  - Role of oxidant injury on macrophage lipoprotein lipase (LPL) production and
      sensitivity to LPL.
AB  - We investigated, in the present study, the role of reactive oxygen intermediates
      (ROI) in the control of macrophage lipoprotein lipase (LPL) secretion. Exposure
      of murine macrophages to increasing concentrations of hydrogen peroxide (H2O2)
      resulted in enhanced basal LPL production and mRNA levels. The increase of LPL
      production was reduced in the presence of antioxidants. Oxidant stress also
      modulated the regulation of macrophage LPL production by tumor necrosis factor
      alpha (TNF alpha). While antioxidants accentuated the inhibition of LPL by TNF
      alpha, addition of H2O2 significantly attenuated TNF alpha-induced LPL
      inhibition. As LPL has been shown to induce macrophage TNF alpha release, the
      effect of reactive oxygen species on LPL-induced TNF alpha production was also
      examined. Simultaneous treatment of macrophages with LPL and H2O2 or pretreatment
      of macrophages with H2O2 prior to LPL stimulation decreased the LPL-induced TNF
      alpha release by macrophages to the same extent. Under these experimental
      conditions, LPL binding to macrophages was markedly decreased. These data
      indicate that ROI are effective enhancers of macrophage LPL production and
      modulate macrophage response to LPL. These effects may represent additional
      mechanisms through which oxidant stress may participate to the development of
      atherosclerosis.

PMID- 8732781
TI  - Effect of ethanol on the synthesis and secretion of apoA-I- and apoB-containing
      lipoproteins in HepG2 cells.
AB  - The short- and long-term effects of ethanol on the production of lipids and
      apolipoproteins (apo) in HepG2 cells were studied. Short-term incubation with 1%
      ethanol caused a significant 32% increase in the cellular content of both
      triglycerides and cholesteryl esters. Under these conditions, the net
      accumulation in the medium of triglycerides, unesterified cholesterol,
      cholesteryl esters, apoA-I, and apoE was stimulated by 75%, 41%, 43%, 19%, and
      39%, respectively. ApoA-I and apoE mRNA levels increased by 15%. The major short
      term effect of ethanol was on the net accumulation of apoB in the medium which
      was stimulated by 56-100% in the presence of 0.1-1.0% ethanol. Under these
      conditions, apoB mRNA abundance was elevated by 17-26% and LDL receptor activity
      was unchanged. The increase in apoB accumulation in the medium was predominantly
      due to augmented secretion of newly synthesized apoB-100 which was evident at
      0.05% ethanol. The secretion of newly synthesized apoA-I was not altered by short
      term incubation with < or = 0.5% ethanol. The rate of apoB production was
      positively correlated with the cellular and secreted cholesteryl esters and
      secreted triglycerides. Addition of Pfizer CP-113,818, an inhibitor of acyl
      CoA:cholesterol acyltransferase, caused a 69% reduction in the secretion of
      cholesteryl esters and a 24% decrease in that of apoB-100. In contrast to the
      short-term effect of ethanol, long-term incubation with ethanol resulted in a
      dose-dependent increase in the secretion of newly synthesized apoA-I without
      significantly affecting that of apoB-100. The increase in apoA-I secretion was
      evident at 0.05% ethanol and reached a maximum of 77% at 0.5% ethanol. These
      observations indicate that in HepG2 cells the effect of ethanol on the production
      of apoA-I- and apoB- containing lipoproteins is both time- and dose-dependent and
      is different in these two apolipoproteins.

PMID- 8732782
TI  - A compound heterozygote for hepatic lipase gene mutations Leu334-->Phe and Thr383
      ->Met: correlation between hepatic lipase activity and phenotypic expression.
AB  - We have characterized the molecular basis for familial hepatic lipase (HL)
      deficiency in a Finnish family. In the propositus, the HL deficiency results from
      compound heterozygosity for two rare HL gene mutations, a previously unknown
      missense mutation designated L334F and the previously reported T383M mutation.
      These mutations were introduced into human HL cDNA by site-directed mutagenesis
      and the constructs expressed in COS-1 cells. In the homogenate of COS-1 cell
      transfected with the L334F mutant cDNA, a high amount of inactive protein
      accumulated. In the media of L334F transfected cells, 30% of the wild type
      activity and 80% of wild type mass were detected. The lysates of COS-1 cells
      transfected with the T383M mutant cDNA contained 39% of wild type HL activity and
      34% of wild type HL mass. In the media of COS-1 cells transfected with the T383M
      cDNA construct, 50% of wild type HL mass but only 6% of wild type activity was
      present. The single amino acid substitutions present in L334F and T383M are
      therefore sufficient to severely affect the HL enzyme. These defects explain the
      HL-deficient phenotype of the individual carrying the two mutations. The
      lipoprotein phenotype associated with compound heterozygosity for L334F and T383M
      mutations is characterized by a slight increase in the buoyant low density
      lipoprotein (LDL) fraction and an increase in the light high density lipoprotein
      (HDL) fractions, HDL2a and HDL2b. These results demonstrate that lipoprotein
      changes occurring in HL deficiency are difficult to identify and support the
      hypothesis that HL is important in HDL remodeling and metabolism in vivo.

PMID- 8732783
TI  - Macrophage oxidative modification of low density lipoprotein occurs independently
      of its binding to the low density lipoprotein receptor.
AB  - The oxidative modification of low density lipoproteins (LDL) by arterial wall
      cells is thought to contribute to atherogenesis. Monocyte/macrophages, among
      other arterial wall cells, oxidatively modify LDL to a form that is recognized by
      scavenger/oxidized LDL receptors. It has recently been suggested that LDL binding
      to the LDL receptor (B/E receptor) is essential for macrophage-mediated oxidation
      of LDL. In the present study, we compared the ability of resident peritoneal
      macrophages from LDL-R-deficient (LDLR-/-) mice to oxidize LDL with that of
      resident peritoneal macrophages from C57B6 mice. The LDLR-/- macrophages oxidized
      LDL at least as rapidly as did the C57B6 macrophages both in F-10 medium and in
      Dulbecco's modified Eagle's medium supplemented with 1 microM copper (DMEM-Cu2+).
      Studies were also conducted to examine the effect of preincubation of LDLR-/- and
      C57B6 macrophages with 10% lipoprotein-deficient serum (LPDS), which up-regulates
      LDL receptors, or with acetylated LDL (Ac-LDL), which increases cellular
      cholesterol and down-regulates LDL receptors. Preincubation with 10% LPDS had no
      significant effect on subsequent LDL oxidation by either type of cells in F10
      medium, but the C57B6 cells did show a small (18%) but significant increase in
      LDL oxidation in DMEM-Cu2+. Preincubation with 50 micrograms/ml Ac-LDL in F10
      medium had no effect on LDL oxidation by either LDLR-/- or C57B6 macrophages.
      Preincubation with 100 micrograms/ml Ac-LDL had no effect on subsequent LDL
      oxidation by C57B6 cells but, unexpectedly, caused a modest (26%) fall in LDL
      oxidation by the receptor-negative cells. Using DMEM-Cu2+ medium, preincubation
      with Ac-LDL reduced LDL oxidation substantially (50-66%) but the effect was just
      as great in LDL-R negative cells (59-66%) as in C57B6 cells (50-58%), suggesting
      that the effect is not due to changes in LDL receptor density. It may be related
      somehow to the Ac-LDL-induced increase in cell cholesterol content. The data
      demonstrate that the absence of LDL receptors does not reduce the ability of
      macrophages to oxidize LDL and that LDL binding to LDL receptors is not an
      essential requirement for macrophage oxidation of LDL.

PMID- 8732784
TI  - Positive linear correlation between the length of truncated apolipoprotein B and
      its secretion rate: in vivo studies in human apoB-89, apoB-75, apoB-54.8, and
      apoB-31 heterozygotes.
AB  - Apolipoprotein B (apoB), the major protein component of triglyceride-rich
      lipoproteins secreted from the liver, plays crucial roles in the secretion,
      transport, and receptor-mediated clearance of lipoproteins. A minority of cases
      of familial hypobetalipoproteinemia is due to genetically determined truncations
      of apoB-100 that range in size from apoB-9 to apoB-89, but truncated apoBs
      smaller than apoB-27.6 were not detected in plasma. To ascertain the physiologic
      bases of the hypobetalipoproteinemia, we studied in vivo metabolic parameters of
      the products of both the normal and mutant apoB alleles in human apoB
      truncation/apoB-100 heterozygotes (apoB-89/apoB-100, n = 2, apoB-75/apoB-100, n =
      2; apoB-54.8/apoB-100, n = 6; apoB-31/apoB-100, n = 1) using endogenous labeling
      with [13C]leucine, mass spectrometry, and multicompartmental modeling. All
      truncated forms of apoB were secreted at reduced rates. The secretion rates of
      apoB-89, apoB-75, apoB-54.8, and apoB-31 were 92%, 64%, 37%, and 12%,
      respectively, of the respective apoB-100s on a molar basis. Additionally,
      particles containing apoB-89, apoB-75, and apoB-54.8 had increased fractional
      catabolic rates (FCR), while apoB-31-containing particles had a decreased FCR. On
      regression analysis, the secretion rate was linearly linked to the length of the
      truncated apoB (r2 = 0.86, P < 0.0001), with secretion being reduced by 1.4% for
      each 1% of apoB truncated. The linear regression line of apoB size versus apoB
      secretion rate has a zero intercept for apoB secretion at apoB-28, which is
      consonant with the apparent absence in plasma of truncations smaller than apoB
      25. We conclude that secretion of apoB in vivo is dependent on the length of the
      truncation of apoB, possibly because the smaller the truncated apoB, the less it
      is protected from intracellular degradation.

PMID- 8732785
TI  - A rapid and simple screening test for potential inhibitors of tocopherol-mediated
      peroxidation of LDL lipids.
AB  - We report a rapid and convenient method for screening potential inhibitors of the
      initiation of low density lipoprotein (LDL) lipid peroxidation. The method uses
      positively and negatively charged micelles of either cetyltrimethyl ammonium
      chloride or sodium dodecyl sulfate with added alpha-tocopherol. It is based on
      the capacity of an antioxidant to attenuate alpha-tocopheroxyl radicals,
      generated by irradiation of the alpha-tocopherol-containing micelles with UV
      light, and measured directly by electron spin resonance spectroscopy. To
      establish the reliability of the method, we compared the alpha-to-copheroxyl
      radical attenuating ability (TRAA) of 53 natural and synthetic potential
      antioxidants with their respective ability to inhibit the early stages of LDL
      lipid peroxidation initiated by a low flux of water-soluble peroxyl radicals. The
      relationship between the measured TRAA and corresponding LDL antioxidation
      activity was highly significant (P < 0.00005, Rank test). Thus, the potency of a
      co-antioxidant for LDLs alpha-tocopherol could be predicted with > 98%
      probability by the TRAA test alone. The results suggest that this relatively
      simple method represents an effective and simple screening test that can be used
      for large numbers of potential inhibitors of the early stages of LDL lipid
      oxidation.

PMID- 8732786
TI  - New fluorogenic triacylglycerol analogs as substrates for the determination and
      chiral discrimination of lipase activities.
AB  - A new type of fluorogenic and isomerically pure 1(3)-O-alkyl-2,3 (3,2)-diacyl
      glycerols was synthesized that can be used as substrate for the determination of
      lipase activities. These compounds contain a fluorescent pyrene acyl chain and,
      as a potent quencher of pyrene fluorescence, a trinitrophenylamino acyl residue.
      In their intact form, the fluorogens show only low fluorescence intensity. Upon
      lipase-induced or chemical hydrolysis of the substrates, however, the fluorophore
      and quencher separate from each other. This leads to a gradual increase in pyrene
      fluorescence, reflecting the time-dependent progress of lipolysis and, under
      substrate saturation conditions, lipase activity. This lipase assay is continuous
      and does not require separation of substrate and reaction products. Short- and
      long-chain homologues as well as optical isomers of the fluorogenic alkyldiacyl
      glycerols were hydrolyzed by pancreatic lipase, hepatic lipase, and lipo-protein
      lipase at highly different rates depending on the substrate or enzyme preparation
      and source (e.g., postheparin plasma or cultured cells). It is proposed that a
      useful set of enantiomeric and/or homologous substrates in combination with
      appropriate reaction media might be applied to the selective determination of a
      lipase in a mixture of lipases, e.g., hepatic and lipoprotein lipase in PHP, for
      medical diagnostics.

PMID- 8732787
TI  - A novel vesicular assay to study factors affecting cholesterol crystallization in
      vitro.
AB  - We present an assay to study cholesterol crystallization that is fast, facile,
      and highly reproducible. Cholesterol crystallization from metastable vesicles was
      induced upon addition of bile salts and depended on the hydrophobicity of the
      bile salt used and the cholesterol-to-phospholipid ratio of the vesicles. Bile
      salt-induced crystallization was stimulated upon addition of Con A-binding
      glycoproteins (CABGs), comparable to the results of the same CABGs in a crystal
      growth assay. The onset time and total measuring time, however, were much
      shorter. This assay might, moreover, provide a tool to study the mechanism of
      cholesterol crystallization in more detail.

PMID- 8732788
TI  - Selection of monoclonal antibodies for linear epitopes of an apolipoprotein
      yields antibodies with comparable affinity for lipid-free and lipid-associated
      apolipoprotein.
AB  - A direct approach is described for generating human apolipoprotein (apo) A-I
      specific monoclonal antibodies with defined linear epitopes. The antibodies have
      comparable binding affinity for delipidated apoA-I and apoA-I on high density
      lipoproteins (HDL). The antibodies were obtained by immunizing mice with HDL,
      screening the fusions first for antibodies that bind native HDL and second, for
      antibodies that bind defined apoA-I synthetic peptides. ApoA-I antibody epitopes
      assigned on the basis of synthetic peptide binding were confirmed by solid phase
      and fluid phase antibody competition assays. These antibodies, which bind
      epitopes that encompass greater than 60% of apoA-I, should prove useful for
      identifying discrete functional domains of apoA-I on HDL.

PMID- 8732789
TI  - Simultaneous determination of tissue tocopherols, tocotrienols, ubiquinols, and
      ubiquinones.
AB  - A tissue-specific distribution of the various vitamin E forms, tocotrienols and
      tocopherols, has been found, suggesting that these forms have unique roles in
      cellular functions. A sensitive procedure is described for the simultaneous
      determination of individual tocopherols, tocotrienols, ubiquinols, and
      ubiquinones using gradient high pressure liquid chromatography (HPLC) and
      electrochemical detection for vitamin E homologues and ubiquinols, and in-line UV
      detection for ubiquinones. Using this method, the lipophilic antioxidant
      complement of a variety of hairless mouse tissues was analyzed. Of the vitamin E
      forms, brain contained virtually only alpha-tocopherol (5.4 +/- 0.1 nmol/g;
      99.8%) and no detectable tocotrienols were found. By contrast, skin contained
      nearly 15% tocotrienols and 1% gamma-tocopherol. In other tissues, the alpha
      tocopherol content was higher (20 nmol/g), while each of the other forms
      represented about 1% of the total (gamma-tocopherol 0.2 to 0.4 nmol/g, alpha
      tocotrienol 0.1, gamma-tocotrienol 0.2). Ubiquinol-9 concentrations were highest
      in kidney (81 nmol/g) and in liver (42 nmol/g), while the highest ubiquinone-9
      concentrations were found in kidney (301 +/- 123 nmol/g) and heart (244 +/- 22
      nmol/g). Liver contained nearly identical concentrations of each of the redox
      couple (ubiquinol-9 (41 +/- 16 nmol/g) and ubiquinone-9 (46 +/- 18 nmol/g). The
      unique distribution of these various antioxidants in the tissues measured
      suggests their distribution may be dependent upon selective mechanisms for
      maintaining antioxidant defenses in each tissue.

PMID- 8732790
TI  - Apolipoprotein H: a two-step isolation method.
AB  - A new method for the purification of apolipoprotein H by affinity chromatography
      followed by continuous-elution electrophoresis is described. It is both simpler
      and less complicated than the chromatographic and electrophoretic methods usually
      used. In addition, apolipoprotein H is isolated in a pure, structurally uncleaved
      form. This is of importance, as impairment has been detected in commercial
      preparations. The separation and purification of apolipoprotein H is a necessary
      prelude to its quantitative determination and phenotyping, and hence the
      clarification of its physiopathological mechanisms in lipid metabolism.

PMID- 8732791
TI  - Managed care and the rheumatologist.

PMID- 8732792
TI  - Update on the epidemiology of the rheumatic diseases.
AB  - Epidemiologic studies continue to enhance our understanding of the rheumatic
      diseases. Such studies now indicate that 26 million American women are at risk
      for osteoporotic fractures. Contrary to previous recommendations, the
      identification and treatment of patients at risk for osteoporosis may be valuable
      even among very elderly people. Other epidemiologic studies suggest that the
      incidence of rheumatoid arthritis is decreasing and that it is a more benign
      disease than previously recognized. Osteoarthritis remains a leading cause of
      physical and work disability in North America. The roles of occupational physical
      activity, obesity, and highly competitive (though not low-impact) exercise as
      risk factors for osteoarthritis continue to be explored. Pharmacoepidemiologic
      research has recently demonstrated that a policy of prior authorization for
      prescription of nonsteroidal anti-inflammatory drugs may be highly cost
      effective. Finally, controlled epidemiologic studies have not confirmed an
      association between silicone breast implants and connective tissue diseases, a
      conclusion recently endorsed by the American College of Rheumatology.

PMID- 8732793
TI  - Update on measurement of relevant outcomes in rheumatology.
AB  - It is now recognized that disease has a multidimensional impact on patients'
      lives. This impact can be perceived as a spectrum encompassing on one end "hard"
      disease outcomes such as organ failure and mortality, and on the other end "soft"
      outcomes such as quality of life or patient satisfaction. This spectrum may be
      viewed as a framework in measuring both disease impact and response to treatment.
      In this paper, we review improvements in the methodology of measurement of
      relevant outcomes and highlight new findings and emerging trends in rheumatology.

PMID- 8732794
TI  - Health services research and policy studies.
AB  - Health services research in rheumatology is producing important studies that have
      implications for the provision of care in a changing health care environment.
      This paper reviews studies relating to issues surrounding the delivery of care to
      patients, patients' access to medical care, how to provide more cost-effective
      medical care, and who should be providing medical care. The increasing use of
      managed medical care provides researchers with the opportunity to examine how
      changes in medical care delivery affect patient outcomes and the cost of the care
      that is provided. Policy makers need to be made aware of the research being
      conducted in health services so that they make informed policy decisions.

PMID- 8732795
TI  - Fibromyalgia, chronic fatigue syndrome, and myofascial pain.
AB  - The prevalence of fibromyalgia in the general population was found to be 2% and
      increased with age. Multiple traumatic factors, including sexual and physical
      abuse, may be important initiating events. The most important pathophysiologic
      studies in fibromyalgia included evidence of altered blood flow to the brain and
      hypothalamic-pituitary-adrenal dysfunction. The prevalence of chronic fatigue
      syndrome is much less than that of fibromyalgia. Epidemiologic studies
      demonstrated that chronic fatigue and symptoms of fibromyalgia are distributed as
      continuous variables in the general population. No association between chronic
      fatigue and initial infections was seen in primary care practices.

PMID- 8732796
TI  - Epidemiology, etiology, diagnostic evaluation, and treatment of low back pain.
AB  - Epidemiologic studies found mechanical low back pain to be the fifth most common
      reason for visiting a physician. Proteoglycan production is altered with the age
      of the host and may explain the development of degenerative disk disease.
      Important clinical low back pain entities reviewed in the literature include
      exercise-associated degenerative disk disease, sciatica in adults less than 21
      years of age, fibromyalgia, apophyseal and sacroiliac joint pain, and sacral
      insufficiency fractures. No consensus exists among physicians concerning
      appropriate therapy for low back pain. Return to usual activity is the most
      effective therapy, according to a recent study. The first decompression operation
      for spinal stenosis has the best opportunity for a good outcome. Chiropractors
      are the most expensive health care providers for low back pain patients.

PMID- 8732797
TI  - Lower extremity musculoskeletal problems in dancers.
AB  - Ankle and foot problems are extremely common in the high-performance dance
      population. To adequately evaluate and treat these problems, the physician must
      possess knowledge of how the physical demands of dance affect the performer's
      body. A routine evaluation of the dancer, involving a team of orthopedists, dance
      instructors, and physical therapists familiar with dance mechanics, has been
      developed to facilitate recognition of the abnormal mechanics responsible for
      injury. This technique can be useful in prevention and early diagnosis of injury,
      thus minimizing lost performance time.

PMID- 8732798
TI  - Exertional compartment syndromes of the lower extremity.
AB  - Compartment syndromes may be acute or chronic secondary to exertion or exercise.
      The chronic or exertional type most commonly involves the lower extremity,
      particularly the anterior compartment of the lower leg, and is the subject of
      this review. Rarely, an exertional compartment syndrome may become acute. The
      diagnosis is based on history, physical examination, and compartment pressure
      measurements. The differential diagnosis of exertional leg pain includes stress
      fractures, stress reaction, periostitis, claudication, popliteal artery
      entrapment, and peripheral nerve entrapment. Unusual causes, such as a ganglion
      of the proximal tibiofibular joint causing an anterior compartment syndrome, have
      recently been reported.

PMID- 8732799
TI  - Total hip arthroplasty.
AB  - Total hip arthroplasty continues to be an extremely successful procedure, with
      ever-widening indications and regular improvement in technique, materials, and
      design. In the past year several studies were published evaluating the results of
      both cemented and cementless total hip arthroplasty at mid- to long-term follow
      up. In addition, careful analysis of basic laboratory studies including finite
      element analyses have added to our understanding of materials and design.
      Specific findings in the past year included poor results with cemented hips in
      younger patients at long-term follow-up of greater than 16 years. A lower
      incidence of loosening has been found for cobalt chrome-cemented components
      compared with titanium-cemented components. No difference was found in the
      results of metal-backed versus non-metal backed cemented acetabular components,
      and an increasing incidence of loosening was shown for cemented acetabular
      components with time. The newer cementless hip arthroplasties showed evidence of
      learning curve, particularly with regard to innovative design such as acetabular
      screw rings, whereas porous-coated hemispherical cups appeared to do well. Thigh
      pain continues to be a problem with cementless designs, and the controversy of
      titanium versus cobalt chrome for cementless femoral stem designs continues at
      full tilt.

PMID- 8732800
TI  - Recent advances in shoulder surgery.
AB  - Major changes have taken place in the diagnosis and treatment of rotator cuff
      tears. It seems that magnetic resonance imaging alone as a diagnostic tool is
      still not sensitive enough, particularly in the diagnosis of partial tears.
      Arthrography and arthroscopy are still considered essential for an accurate
      preoperative diagnosis. To guarantee a better postoperative result, a carefully
      planned course of preoperative physiotherapy is mandatory. In experienced hands,
      arthroscopic surgery gives results comparable to those obtained with open
      procedures. A careful debridement, anterior acromioplasty, and decompression have
      replaced extensive surgical intervention in the treatment of massive tears. The
      first results in treating calcifying tendinitis with shock-wave therapy seem
      encouraging. A more refined diagnosis of the impingement syndrome is a
      prerequisite for a successful outcome because impingement is not caused by a
      narrowing of the subacromial space in all patients. Increase in contents of this
      space and instability are equally important factors.

PMID- 8732801
TI  - Stress fractures of the sacrum and lower extremity.
AB  - Stress fractures of the lower extremity and sacrum occur in a variety of
      patients, ranging from young, healthy athletes to elderly persons with underlying
      illnesses. Knowledge of the activities and risk factors associated with these
      fractures may heighten clinical suspicion and help direct an appropriate
      evaluation. Diagnosis is usually based on characteristic features of the history
      and physical examination accompanied by radiologic findings. Bone scintigraphy
      remains the standard, but the specificity of computed tomography scanning or
      magnetic resonance imaging may be required to differentiate stress fractures from
      other processes such as malignant bone lesions. Management of stress fractures is
      usually conservative, with variation depending on fracture location and patient
      characteristics.

PMID- 8732803
TI  - Epidemiology and health services research.

PMID- 8732802
TI  - A rehabilitation approach to chronic pain in rheumatologic practice.
AB  - There have been several recent studies of the epidemiology and costs attributable
      to the chronic pain and chronic fatigue syndromes. Although investigations of the
      putative mechanisms of these disorders continue, there remains a poor
      understanding of their underlying pathophysiology. Four studies are reviewed that
      further support the commonality of both physical symptoms and psychological
      distress in chronic pain and chronic fatigue syndromes. By considering these
      commonalities, a comprehensive behavioral-rehabilitative approach can be
      undertaken to assist patients in addressing their adaptive difficulties. An
      overview of admission criteria for pain rehabilitation services is provided.
      Finally, recent empirical studies of both treatment process and outcome provide
      further support for the effectiveness and long-term benefits of this approach.

PMID- 8732804
TI  - Nonarticular rheumatism, sports-related injuries, and related conditions.

PMID- 8732805
TI  - Number, size, and regional distribution of motor neurons in the dorsolateral and
      retrodorsolateral nuclei as a function of sex and neonatal stimulation.
AB  - Motor neurons were measured in the retrodorsolateral nucleus (RDLN) and the
      dorsolateral nucleus (DLN) of adult male and female rats that were reared with
      normal or reduced levels of maternal anogenital stimulation. In contrast with
      findings for the spinal nucleus of the bulbocavernosus, which is located in the
      same spinal segments, reduced stimulation had no effect on neuron number in
      either nucleus. However, several regional and sex differences were observed.
      Rostrally located neurons were larger in both the RDLN and the DLN; these
      location effects were greater in females. There was no sex difference in RDLN
      neuron size, but DLN neurons were larger in females, particularly in the rostral
      region. Females had significantly more cells in the RDLN, a nucleus previously
      considered nondimorphic, whereas males had more DLN neurons. Both regional and
      sex differences may reflect local differences in trophic factors from targets or
      afferents.

PMID- 8732806
TI  - Development of an aspect of executive control: development of the abilities to
      remember what I said and to "do as I say, not as I do".
AB  - Luria's tapping test (tap once when E taps twice, tap twice when E taps once) was
      administered to 160 children (80 males, 80 females) between 3 1/2 to 7 years old.
      Older children were faster and more accurate than younger children, with most of
      the improvement occurring by the age of 6. All children tested demonstrated
      understanding of the instructions during the pretest, and most started out
      performing well, but younger subjects could not sustain this. Over the 16 trials,
      percentage of correct responses decreased, especially among younger subjects.
      Performance here was compared with performance on the day-night Stroop-like task.
      The most common error on both tasks was to comply with only one of the two rules.
      Other errors included tapping many times regardless of what the experimenter did
      and doing the same thing as the experimenter, rather than the opposite. It is
      suggested that the tapping task requires both the ability to hold two rules in
      mind and the ability to inhibit a strong response tendency, that these abilities
      improve between 3-6 years of age, and that this improvement may reflect important
      changes within frontal cortex during this period of life.

PMID- 8732807
TI  - The organization of leg movements in preterm and full-term infants after term
      age.
AB  - In a sample of 13 full-term and 10 preterm infants, the development of kicking
      movements was studied at 6, 12, and 18 weeks (corrected) age. In healthy full
      term infants some characteristics are strikingly stable, such as the duration of
      the flexion and extension phase and the within-joint organization. These
      parameters did not differ in preterm compared to full-term infants. For other
      features, however, developmental changes and differences were observed. Full-term
      infants tended to decrease their kick frequencies slightly with age. In preterm
      infants much higher initial kick rates were found, followed by a steep decrease,
      which resulted in kick frequencies comparable to the full-term levels after the
      (corrected) age of 12 weeks. There is a tight coupling between the movements in
      the different joints of the leg in full-term newborns. Preterm infants, in
      contrast, initially show much lower cross-correlations between hip and ankle and
      between knee and ankle. This is particularly the case for those preterm infants
      who were born before 32 weeks gestation. Again, the differences resolved after
      the age of 12 weeks, which might be related to a transformation in neural
      functions reported previously around this age. The initial differences in the
      characteristics of kicking appeared to be more readily explainable by differences
      in neurological condition than by contrasts in leg volume or postural control.

PMID- 8732808
TI  - Effects of altered olfactory experiences on the development of infant rats'
      responses to odors.
AB  - A "natural" olfactory learning paradigm was used to assess the effects of an
      altered perinatal olfactory environment on the development of odor-elicited
      behavior in young rats. Infant rats (from 3 to 12 days of age) reared by dams fed
      a eucalyptol-adulterated diet responded to the odor of eucalyptol with high
      levels of activity, mouthing, and probing, and also demonstrated a marked
      preference for that odor in a two-choice situation (Experiment 1). The effects
      were observed only in pups whose dam was fed eucalyptol-adulterated diet and were
      not observed in pups exposed to nonmaternal sources of odor. The intensity of
      behavioral activity elicited by eucalyptol odor varied, to some extent, with the
      concentration of the eucalyptol in the dam's diet during prenatal exposure
      (Experiment 2). Cross-fostering revealed that these effects were due almost
      entirely to the pups' postnatal exposure to the eucalyptol odor (Experiment 3).
      These findings indicate that novel odors specifically associated with the mother
      can gain control over orientation and ingestion-related behaviors.

PMID- 8732809
TI  - Psychophysiological correlates of infant temperament: stability of behavior and
      autonomic patterning from 5 to 18 months.
AB  - The stability of infant temperament and autonomic patterning (heart period and
      cardiac vagal tone) was examined longitudinally when infants were 5, 10, and 18
      months of age. Behavioral measures of reactivity and regulation to frustration
      tasks, and maternal perceptions of infant temperament were obtained at each age
      along with baseline measures of cardiac activity. No stability was found from 5
      to 10 months while some stability of behavior and autonomic patterning was
      identified from 10 to 18 months, with the exception of negative reactivity. High
      levels of cardiac vagal tone (V) were associated with negative reactivity at 18
      months. When examining groups based on degrees of reactivity and regulation, we
      found infants who responded negatively to frustration but who also displayed more
      regulatory behavior to have higher V.

PMID- 8732810
TI  - Does impedance cardiography reliably estimate left ventricular ejection fraction?
AB  - OBJECTIVE: The objective of our study was to evaluate impedance cardiography
      (IMP) as a noninvasive method to determine the left ventricular ejection fraction
      (LVEF). METHODS. A total of 24 patients, 8 men and 16 women, aged 45.0 +/- 12.9
      years, participated in the study. They used cardiotoxic chemotherapeutic drugs or
      suffered from cardiac failure. LVEF was measured by means of IMP (LVEFimp) and
      radionuclide ventriculography (LVEFnuc). LVEFimp was calculated in three ways.
      Capan and colleagues [13] proposed a formula in which LVEF (LVEFCap) can be
      calculated from the systolic time intervals, namely, left ventricular ejection
      time and preejection time. Judy and colleagues [14] described a systolic (S) and
      a diastolic (D) part in the first derivative curve of the impedance signal. The
      ratio S/D might equal the LVEF (LVEFJud). A new LVEF calculation was introduced
      (LVEFimp) in this study based on the first derivative of the impedance signal,
      the thoracic impedance, and heart rate. RESULTS: Mean LVEFCap was 59.9 +/- 8.4%,
      which did not differ from LVEFnuc (59.9 +/- 7.1%). However the correlation
      between both methods was not significant (r = 0.29). Mean LVEFJud was 63.9 +/-
      17.4%, which was not significantly different from LVEFnuc, with a fair
      correlation (r = 0.55). Mean LVEFimp was 59.2 +/- 9.4%, with a better correlation
      with radionuclide ventriculography (r = 0.75). CONCLUSIONS: The results of this
      study indicate that the equations that have been used until now can be improved.
      The new equation provides reliable LVEF values in this group of patients.

PMID- 8732811
TI  - Evaluation in animals of a system to estimate tracheal pressure from the
      endotracheal tube cuff.
AB  - OBJECTIVE: Flow through an endotracheal tube (ETT) causes a pressure loss across
      the tube. This loss results in a difference between pressure measured at the
      airway and pressure measured in the trachea. This difference can lead to errors
      when calculating pulmonary mechanics and when setting ventilators. We have tested
      a method of estimating tracheal pressure from the pressure in the ETT cuff.
      METHODS: Pressure transducers were placed in the proximal ETT connector, in the
      trachea, and in the ETT cuff (through the inflation port). Instantaneous periods
      of zero flow, detected with a flow meter, were used to calculate the slope and
      offset of the line relating cuff pressure to tracheal pressure. The system was
      tested on the bench using a ventilator and lung simulator and in 2 dogs and 5
      pigs. Tests were performed at various cuff pressures, trachea diameters, ETT
      sizes, respiratory rates, tidal volumes, and airway obstructions. RESULTS: In
      bench tests, our estimate of tracheal pressure was within -4.0 +/- 2.6% of the
      actual tracheal pressure (mean +/- standard deviation [SD]). In animal tests, our
      estimation of tracheal pressure was within -0.6 +/- 5%. In all bench test
      measurements and in 40 of 42 animal measurements, the error was less than 1 cm
      H2O. CONCLUSIONS: The cuff estimation technique gives real-time, continuous,
      noninvasive tracheal pressure measurements in intubated animals with cuffed ETTs.

PMID- 8732812
TI  - A new system to record reliable pulse oximetry data from the Nellcor N-200 and
      its applications in studies of variability in infant oxygenation.
AB  - We have developed a simple system for internal validation of oximetry data
      collected over many hours from the Nellcor N-200 pulse oximeter (Nellcor, Inc.,
      Hayward, CA). This system uses signals from the oximeter alone and a validation
      algorithm that is based in a computer connected to the oximeter. Unlike other
      validation systems, this system does not require connections to other monitors.
      The system was tested on 10 acutely ill newborns in an intensive care nursery
      over 16 hr of continuous recording for each infant (birthweight, 2.50 +/- 0.73
      kg; age, 3.4 +/- 3.2 days). Oximetry data were accepted as valid using the new
      system if they surpassed a minimum level of quality (empirically derived, and
      equal to a 60% fractional success in pulse detection). The validated oximetry
      data were compared to data obtained using a conventional "compared to the
      electrocardiogram (ECG)" algorithm. For the new and the conventional algorithms,
      the distributions of validated SpO2 percents were nearly identical, with data
      rejection rates of 28.9% for the new system and 37.3% for the conventional
      system. In the newborns, the new system was used to demonstrate that as the mean
      saturations decreased, there were striking increases in variability about the
      reported mean saturation (p < 0.001). While variability in infant SpO2 is a well
      known phenomenon, the amount seen here was unexpected. For example, the range of
      true saturations frequently recorded was quite wide at a reported mean SpO2 of
      90% (from 81 to 94%; but, the range was only from 92 to 98% at a mean SpO2 of
      96%). These findings demonstrate the usefulness of the new system and, if
      substantiated in more detailed studies, have important implications for the use
      of pulse oximeters to assess oxygenation in newborns.

PMID- 8732813
TI  - Blood glucose reagent strip tests in the operating room: influence of hematocrit,
      partial pressure of oxygen, and blood glucose level--a comparison of the BM-test
      1-44, BM-Accutest, and Satellite G reagent strip systems.
AB  - OBJECTIVE: The objective of our study was to assess the influence of hematocrit
      (HCT), partial pressure of oxygen (PO2), and blood glucose level upon results
      obtained with three different blood glucose reagent strip tests used in
      conjunction with the appropriate meter: BM-Test 1-44, BM-Accutest, and Satellite
      G. METHODS: Our study was designed as a consecutive sample study of patients
      undergoing coronary artery surgery. The setting was the hospital theater and
      intensive care unit. We conducted blood analysis for HCT, PO2 and blood glucose
      on 20 consecutive patients undergoing coronary artery surgery using three blood
      glucose reagent strip testing systems and a laboratory analysis of plasma
      glucose. RESULTS: All three blood glucose reagent strip tests showed a
      significant bias when compared with plasma glucose: BM-Test 1-44, 0.89 mmol/L; BM
      Accutest, -1.27 mmol/L; Satellite G, 0.75 mmol/L (p < 0.05). The error found when
      using the Satellite G system was worse than that of either of the other two
      systems. Results obtained with the BM-Accutest strips were unaffected by PO2 (p =
      0.745). Blood glucose value and HCT both had an influence on the results of all
      three blood glucose strip systems. CONCLUSIONS: Caution must be taken when using
      reagent strip systems in the operating room or intensive care setting because, of
      the three systems tested, all showed a significant bias, all were influenced by
      blood glucose level and HCT, and only the BM-Accutest reagent strips used with
      the Accutrend meter was unaffected by PO2.

PMID- 8732814
TI  - Pro: there is nothing wrong with old anesthesia machines and equipment.

PMID- 8732815
TI  - Con: there is nothing wrong with old anesthesia machines and equipment.

PMID- 8732816
TI  - Use of adaptive Hilbert transformation for EEG segmentation and calculation of
      instantaneous respiration rate in neonates.
AB  - Broad, as well as narrow, band Hilbert transform filters (HTFs) were used as
      preprocessing units in the analysis of electroencephalogram (EEG) and respiratory
      movements in neonates. For these applications, new algorithms for the adaptation
      of the resonance frequency of a narrow-band-pass filter to the actual signal
      properties on the basis of an analytic filter design were developed. For the
      segmentation of the discontinuous EEG, the location of the resonance frequency
      was imbedded into the learning algorithm of a neural network (NN). In such
      automatic EEG pattern recognition, the detection of spike activity was taken into
      consideration. The spike detection scheme introduced uses broad-band HTFs as
      basis units. Additionally, the algorithm for the continuous control of the
      resonance frequency was applied to achieve the adaptation of the processing unit
      that performed the calculation of the instantaneous respiration rate, in this
      framework, a new on-line method for adaptive frequency estimation that is less
      sensitive to low signal-to-noise ratios (SNRs) was obtained. The new approaches
      introduced were tested in comparison with processing methods that have been
      established for the analysis of experimental and clinical data.

PMID- 8732817
TI  - Automated system for detailed measurement of respiratory mechanics.
AB  - OBJECTIVE: The mechanical properties of the respiratory system (i.e., elastance
      and resistance) depend on the frequency, tidal volume, and shape of the flow
      waveform used for forcing. We developed a system to facilitate accurate
      measurements of elastance and resistance in laboratory and clinical settings at
      the frequencies and tidal volumes in the physiologic range of breathing. METHODS:
      A personal computer (PC) is used to drive a common clinically used ventilator
      while simultaneously collecting measurements of airway flow, airway pressure, and
      esophageal pressure from the experimental subject or animal at different
      frequencies and tidal volumes. Analysis analogous to discrete Fourier transform
      at the fundamental frequency (i.e., ventilator setting) is used to calculate
      elastances and resistances of the total respiratory system and its components,
      the lungs and the chest wall. We have shown that this analysis is independent of
      the high-frequency harmonics that are present in the waveform from clinical
      ventilators. RESULTS: The system has been used successfully to make measurements
      in anesthetized/paralyzed dogs and awake or anesthetized human volunteers in the
      laboratory, and in anesthetized human volunteers in the laboratory, and in
      anesthetized humans in the operating room and intensive care unit. Elastances and
      resistances obtained with this approach are the same as those obtained during
      more controlled conditions, e.g., sinusoidal forcing. CONCLUSIONS: Accurate,
      standardized measurements of lung and chest wall properties can be obtained in
      many settings with relative ease with the system described. These properties, and
      their frequency and tidal volume dependences in the physiologic range, provide
      important information to aid in the understanding of changes in respiratory
      function caused by day-to-day conditions, clinical intervention and pathologies.

PMID- 8732818
TI  - Monitoring oxygenation and ventilation during magnetic resonance imaging: a
      pictorial essay.

PMID- 8732819
TI  - Accidental pulmonary barotrauma: a tale of circuit DYS-connects.

PMID- 8732820
TI  - Simulators for anesthesia.
AB  - Two commercially available complete anesthetic simulators were studied in the
      United States. Although there are some differences between the two systems, each
      consists of an adult manikin allowing some direct anesthetic interventions, a
      system of producing physiologic signals to any commercial monitoring system, and
      the ability to interface with an anesthetic machine and ventilator. In addition,
      both simulators model the responses to a variety of drugs used by anesthetists.
      With their associated computer controls, it is possible to mimic a number of
      recognized anesthetic critical situations and to record the responses made by the
      anesthetist and determine the effects on the "patient." In use, one system is
      devoted principally to teaching crisis resource management to anesthetists. The
      other system is used more generally to teach anesthetists how to approach a
      variety of problems. In our opinion, each system could be used in either of these
      ways. Both systems are capable of development into valuable teaching tools for
      anesthetists and for others involved in critical care. There is potential for the
      training of paramedics or nurses involved in anesthetic and recovery room care
      and intensive care. Other options include the investigation of critical events
      and the development and subsequent testing of clinical management protocols.
      Anesthetists are familiar with the use of manikins in the teaching of airway
      management and basic and advanced life support. Newer manikins can be used to
      practice skills in intravascular cannulation; some can be used with monitoring
      equipment and defibrillators to provide more realistic teaching. Computer
      programs, especially those for personal computers (PCs), can also be used to
      simulate the pharmacophysiologic behavior of patients in a variety of states. Now
      available are combined systems using manikins controlled by computer, with
      interfaces to anesthetic machines, ventilators, and monitoring equipment. Two
      systems are commercially available in the United States. In this report, we
      briefly describe their technical specifications and how we saw them being used.

PMID- 8732821
TI  - Signs of safe sedation researched, reviewed.

PMID- 8732822
TI  - Recurrent issues prompt call for continued effort.

PMID- 8732823
TI  - IARS annual meeting includes safety topics.

PMID- 8732824
TI  - Safety of 5% lidocaine heavily defended.

PMID- 8732825
TI  - OR reading debate continues in my opinion: lack of outcome data makes reading a
      personal decision, states OR investigator.

PMID- 8732826
TI  - Linear approximation of Brody's equation to predict oxygen consumption.

PMID- 8732827
TI  - Oblique angle bone SPECT imaging of the lumbar spine, pelvis, and hips. An
      anatomic study.
AB  - Bone SPECT offers advantages over planar imaging in detecting skeletal lesions
      because of increased contrast enhancement and tomographic effect with the latter,
      allowing for precise anatomic localization of an uncovered abnormality. However,
      tomographic sections of curved structures or regions obliquely oriented to the
      reconstruction plane may have inherent limitations as far as case of image
      interpretation, which can be overcome by oblique reorientation of the SPECT
      views. A method for oblique angle presentation of the lumbar spine, pelvis, and
      hips has been developed with results correlated with radiographic tomograms of a
      phantom to order to ensure correct anatomic orientation. These oblique SPECT
      images allow for easier differentiation between facet and pars interarticularis
      abnormalities, as well as improved imaging of hips and sacrum.

PMID- 8732828
TI  - Thyroid imaging with Tc-99m MIBI in patients with solitary cold single nodules on
      pertechnetate imaging.
AB  - Thyroid imaging was performed in 30 patients with the standard pertechnetate
      technique, as well as with Tc-99m MIBI using a double-phase acquisition protocol.
      All patients had normal thyroid function confirmed by hormone measurements and
      cold solitary thyroid nodules, which were evaluated by pertechnetate scanning. Tc
      99m MIBI scans were reported as showing cold (N = 14), warm (N = 7), or hot (N =
      9) nodules. Nodule classification was made according to fine needle aspiration
      biopsy findings in 20 patients. The remaining 10 proceeded to surgery and had
      histopathologic confirmation of their lesions. Although all cold nodules with Tc
      99m MIBI were cystic, six of the warm nodules were benign lesions. No
      histologically proven benign nodule was hot with Tc-99m MIBI. Of the hot nodules,
      seven were suspicious for follicular carcinoma with fine needle aspiration biopsy
      (N = 3), or had histologically proven papillary carcinoma (N = 4). Delayed images
      in five of seven of these lesions showed nodular retention of the
      radiopharmaceutical. In conclusion, double-phase Tc-99m MIBI scanning of the
      thyroid gland could be helpful in the preoperative assessment of patients with
      cold solitary thyroid nodules in order to evaluate the malignancy probability of
      these lesions.

PMID- 8732829
TI  - Scintigraphic demonstration of a right-to-left intracardiac shunt in a patient
      with massive pulmonary emboli.
AB  - A case of massive pulmonary embolism resulting in marked pulmonary to systemic
      shunting in a patient with a previously clinically inapparent ventricular or
      atrial septal defect is presented. The various types of unrecognized intracardiac
      shunts and their prevalence in the adult population are discussed.

PMID- 8732830
TI  - Radioisotope bone scanning in chronic osseous sarcoidosis.
AB  - Sarcoidosis is rarely recognized as an osseous manifestations alone. Patients
      with osseous involvement usually have a chronic multivisceral form of the
      disease. The authors report a case of osseous sarcoidosis without other visceral
      involvement. A bone scan was requested to evaluate the extent of the bone
      involvement and explore buttocks pain.

PMID- 8732831
TI  - Tc-99m MIBI brain SPECT of cerebellopontine angle tumors.
AB  - To prospectively evaluate the imaging feasibility of Tc-99m sestamibi brain SPECT
      of cerebellopontine angle (CPA) tumors, seven patients with CPA lesions seen on
      CT or MRI and five normal control subjects underwent brain SPECT using a triple
      headed camera. Five of these patients had acoustic neuromas, one had a
      meningloma, and the other had a vascular loop. Subsequently, four patients
      underwent surgery. In normal control subjects and patients with CPA lesions,
      there was Tc-99m sestamibi activity in the pituitary gland, choroid plexi, and
      extraocular muscles. The uptake in these structures, especially the choroid plexi
      could not be blocked by the oral administration of potassium perchlorate in two
      normal subjects. Four of seven patients with CPA lesions larger than 1.0 cm in
      diameter showed tumor uptake (3 acoustic schwannomas, 1 meningloma). Two small (
      > 1.0 cm in diameter) intracanalicular type acoustic neuromas failed to show
      uptake, despite additional attenuation correction for the petrous bone. There was
      no abnormal uptake in the patient with a vascular loop in the CPA. Preliminary
      data suggest that, with the exception of small intracanalicular neuromas, CPA
      tumors can be imaged using Tc-99m sestamibi brain SPECT.

PMID- 8732832
TI  - Pattern of gastric emptying in patients with systemic sclerosis.
AB  - Gastric emptying studies, using an indigenously prepared radiolabeled solid food
      marker in the form of Indian bread called Chapati, were performed on 13 patients
      with systemic sclerosis. Six patients had limited cutaneous disease and seven had
      diffuse cutaneous disease. Earlier, the procedure was standardized in 30 healthy
      volunteers. Seven of the 13 (54%) patients (five with diffuse and two with
      limited cutaneous disease) had delayed gastric emptying. Most of these patients
      had gastric symptoms. This pattern of gastric emptying may be clinically
      significant, particularly in patients with diffuse cutaneous disease.

PMID- 8732833
TI  - Imaging of transplanted parathyroid tissue in a patient with recurrent
      hyperparathyroidism.
AB  - Parathyroid scintigraphy is useful in detecting residual hyperplastic parathyroid
      tissue in patients who continue to have hyperthyroidism after "total
      parathyroidectomy." Typically, only the neck and mediastinum are imaged. The
      authors report a case in which images of the forearm were helpful in detecting
      hyperplastic autologous transplanted parathyroid tissue.

PMID- 8732834
TI  - Direct lymphatic drainage from the skin of the forearm to a supraclavicular node.
AB  - Lymphoscintigraphy with Tc-99m antimony sulfur colloid was performed on a patient
      with cutaneous melanoma of the left forearm to define the sentinel nodes before
      surgery. The patient was found to have direct lymphatic drainage from the left
      forearm through a clearly seen lymph channel to a sentinel lymph node in the left
      supraclavicular fossa, and drainage through a separate channel to two sentinel
      nodes in the left axilla. Surprising patterns of lymphatic drainage can be seen
      from the forearm, as well as other parts of the skin, and lymphoscintigraphy will
      enable such patients to be identified before sentinel node biopsy.

PMID- 8732835
TI  - Renal scintigraphy in a patient with retroperitoneal fibrosis.

PMID- 8732836
TI  - Superior imaging qualities of Tc-99m MAG-3 in captopril renal scintigraphy
      contributing to the detection of branch artery stenosis.

PMID- 8732837
TI  - Dermoid cyst presenting as a "cold" thyroid nodule.

PMID- 8732838
TI  - Colonic adenocarcinoma metastatic to bone with gross heterotopic bone formation.
      Bone scan appearance with correlative imaging.

PMID- 8732839
TI  - The appearance of malignant fibrous histiocytoma on a three-phase bone scan.

PMID- 8732840
TI  - Detection of a sphenoid bone metastasis using Tc-99m MDP bone SPECT of the skull.

PMID- 8732841
TI  - Bladder-to-duodenal stump reflux simulating a urinoma in a patient with renal and
      pancreaticoduodenal transplantation.

PMID- 8732842
TI  - Ga-67 imaging in bone marrow hyperplasia.

PMID- 8732843
TI  - Artifacts caused by nonionic contrast media and a portacath on a dual-energy x
      ray absorptiometry whole-body composition study.

PMID- 8732844
TI  - Pleural leak localization with Tc-99m pentetate aerosol in an AIDS patient with
      Pneumocystis carinii pneumonia.

PMID- 8732845
TI  - Metastatic Wilm's tumor to the central nervous system. Extraosseous accumulation
      of bone seeking radiopharmaceutical.

PMID- 8732846
TI  - A photopenic region above a renal transplant.

PMID- 8732847
TI  - Congenital generalized fibromatosis. Extraosseous accumulation of bone seeking
      radiopharmaceutical.

PMID- 8732848
TI  - Visualization of protein losing enteropathy in infantile systemic hyalinosis with
      Tc-99m HSA after albumin challenge.

PMID- 8732849
TI  - Delayed presentation of adrenal neuroblastoma.

PMID- 8732850
TI  - Gastrointestinal activity after bone marrow scintigraphy.

PMID- 8732851
TI  - Unusual cause of unilateral pulmonary uptake on stress TI-201 imaging.

PMID- 8732852
TI  - Ipsilateral lymph node uptake of Tc-99m HMPAO WBC in two men with foot
      infections.

PMID- 8732853
TI  - Extensive nonosseous Tc-99m HDP accumulation in B-cell malignant lymphoma.
      Correlation with Ga-67 scintigraphy.

PMID- 8732854
TI  - Three-phase Tc-99m MDP bone scan in reflex sympathetic dystrophy. Appearance and
      resolution of findings in bilateral disease.

PMID- 8732855
TI  - Lung scintigraphy in post-lung transplant bronchial stenosis.

PMID- 8732856
TI  - Lactating breast producing a mismatch on ventilation perfusion lung scan.

PMID- 8732857
TI  - Current readings in nuclear medicine.

PMID- 8732858
TI  - Analysis of ENV V3 sequences from HIV-1-infected brain indicates restrained virus
      expression throughout the disease.
AB  - The isolation of human immunodeficiency virus type 1 (HIV-1) from the
      cerebrospinal fluid (CSF) of asymptomatic virus carriers suggests that the viral
      infection spreading to the brain occurs early during infection. The aim of the
      present study was to investigate whether HIV-1 infection of the brain parenchyma
      also occurs during the early phase of infection. We also wished to compare the
      degree of replication of the virus in the brain at different clinical stages
      associated with HIV-1 infection. With the use of polymerase chain reaction (PCR),
      the viral genomes present in seven of eight brain specimens obtained from two
      asymptomatic HIV-1 carriers and six AIDS patients were amplified. Thereafter, the
      number of viral copies present in each brain specimen was quantified, the third
      variable region (V3) of the gp 120 glycoprotein was sequenced and these results
      compared with the histopathological findings in the tissue. The HIV-1 DNA genome
      was amplified from seven of the eight brain tissues, including the specimens
      obtained from the two asymptomatic carriers. An increased number of viral copies
      in the brain was found in association with histopathological findings of HIV-1
      encephalitis. The analysis of the V3 sequences, however, revealed the presence of
      a homogeneous virus population in the brain at every clinical stage of the
      disease. These results suggest that, although entry of the virus in the
      parenchyma may occur early during infection, HIV-1 replication in the brain is
      constrained until the terminal phase of AIDS encephalitis.

PMID- 8732859
TI  - DNA single strand conformation polymorphism identifies five defined strains of
      hepatitis B virus (HBV) during an outbreak of HBV infection in an oncology unit.
AB  - An outbreak of hepatitis B virus (HBV) infection in a children's oncology unit
      was identified in which 61 children were shown to have been infected, 59 of them
      asymptomatically. In order to establish whether intra-unit cross infection had
      occurred, we used the single strand conformational polymorphism (SSCP) technique
      to analyse viral isolates from 57 of the infected children and 40 unrelated
      controls. HBV-specific primers were designed to amplify a 189 bp fragment of DNA
      encompassing part of the hypervariable pre-S1 region of the HBV genome. Denatured
      PCR products were compared after electrophoresis through polyacrylamide gels and
      staining with silver. By SSCP analysis, the unrelated infections each yielded a
      unique electrophoretic banding pattern, indicative of a variety of distinct virus
      strains. In contrast, most of the oncology patients had been infected with one of
      only five different strains. Three major groups comprising 19, 16, and 9
      patients, respectively, and two minor groups of 5 and 3 patients were identified.
      Results indicate the occurrence of multiple episodes of cross infection, and
      demonstrate the sensitivity and value of SSCP as a technique to establish common
      sources of infection.

PMID- 8732860
TI  - Distribution of HCV genotypes among blood donors, patients with chronic liver
      disease, hepatocellular carcinoma, and patients on maintenance hemodialysis in
      Korea.
AB  - Hepatitis C virus (HCV) is a single-stranded RNA virus related to the
      Flaviviridae family, and striking nucleotide sequence diversity has been reported
      among HCV isolates from different geographic areas. To study the distribution HCV
      genotypes among disease group in Korea, we subtyped HCV using the method of
      Okamoto et al. [(1992a): Journal of General Virology 73:673-679] and the reverse
      hybridization method (INNO-LiPA) on 138 patients who were HCV polymerase chain
      reaction (PCR)-positive: 30 blood donors, 30 with hepatocellular carcinoma (HCC),
      33 with chronic hepatitis, 15 with liver cirrhosis, and 30 patients on
      maintenance hemodialysis in Korea. In 30 blood donors, HCV genotype 1b was most
      dominant (80%), followed by genotype 2a (13.3%), and 2b (6.7%). In 30 HCC cases,
      HCV genotype 1b was less frequent (60%), compared to blood donors, followed by
      genotype 2a (33.3%), and unclassified (6.7%). In 33 chronic hepatitis cases, HCV
      genotype 1b was also dominant (63.6%), followed by genotype 2a (30.3%), and 1a
      (6.1%). In 15 patients with liver cirrhosis, HCV genotype 1b was also dominant
      (60%), followed by genotype 2a (33.3%), and 1a (6.7%). In 30 patients on
      maintenance hemodialysis, HCV genotype 1b was dominant (86.7%), followed by
      genotype 2a (13.3%). In conclusion, among 138 HCV PCR-positive patients, type 1b
      was the prevailing type (71%), followed by type 2a (23.9%), type 1a (2.1%), type
      2b (1.5%), and unclassified (1.5%) in Korea. The prevalence of type 1b in blood
      donors (80%) was higher than in patients with liver disease (61.5%) and the
      prevalence of type 1b was the lowest in patients with HCC (60%).

PMID- 8732861
TI  - Cytomegalovirus antibody avidity in allogeneic bone marrow recipients: evidence
      for primary or secondary humoral responses depending on donor immune status.
AB  - The reconstitution of the human cytomegalovirus (CMV) antibody response in CMV
      seropositive bone marrow transplant patients was investigated by comparing 11
      patients whose donors were CMV seropositive with 8 whose donors were CMV
      seronegative. Evidence for primary or secondary responses to CMV was sought by
      determining IgG antibody avidity using an avidity index method, and antibody
      titre over a period of up to 3 years after transplant. For the patients whose
      donors were CMV seropositive, the results showed the characteristics of a
      secondary response, i.e., rising antibody titres of high avidity immediately
      after transplant. In contrast, the patients with CMV seronegative donors showed
      evidence of a primary antibody response usually occurring at about 250 days after
      transplant, i.e., rising antibody levels initially of low avidity maturing to
      high avidity over the following 100 to 200 days. It is concluded that a secondary
      response and hence transfer of humoral immunity had occurred in those patients
      whose donor was CMV seropositive, whereas a delayed primary response occurred in
      those patients whose donor was CMV seronegative.

PMID- 8732862
TI  - Chronic delta hepatitis: is the prognosis worse when associated with hepatitis C
      virus and human immunodeficiency virus infections?
AB  - Eighty-six patients were followed for 6.5 years to study the epidemiological,
      virological, and histological course of chronic delta hepatitis and the
      relationship of this disease with HIV and HCV infection. Patients were classified
      into four groups according to simultaneous HCV and/or HIV infection: group 1, HDV
      infection (20 cases); group 2, HDV and HCV infection (11 cases); group 3, HDV and
      HIV infection (12 cases), and group 4, HDV, HCV, and HIV infection (43 cases).
      All but 14 patients were asymptomatic at presentation. Liver histology showed
      chronic active hepatitis in 53 cases and cirrhosis in 19 cases. During followup,
      52 patients remained asymptomatic, 34 developed hepatic dysfunction, 28 died, and
      1 received a liver transplant. Among the 28 patients who died, 4 had HDV
      infection; 3 HDV and HCV infection; 3 HDV and HIV infection; and 18 HDV, HCV, and
      HIV infection. Death was due to liver failure in 16 (57%), AIDS in 10 (36%), and
      was unrelated to liver disease in 2 (8%) cases. There results demonstrate that
      chronic delta hepatitis is a severe disease, especially among drug users with HIV
      and HCV infection. The high morbidity and mortality of chronic delta hepatitis
      justifies the use of antiviral therapy to modify the natural course of the
      disease.

PMID- 8732863
TI  - Molecular characterization of Camberwell virus and sequence variation in ORF3 of
      small round-structured (Norwalk-like) viruses.
AB  - Five small round-structured viruses (SRSVs) associated with gastroenteritis in
      Victoria, Australia, from January to November 1994 were examined by sequencing
      cDNA prepared from faecal samples using RT-PCR. The sequence of the 3' half (3.8
      kb) of the genome of one of these viruses, Camberwell, was determined. Camberwell
      virus was related most closely to Bristol and Lordsdale viruses, and belonged to
      the genetic group of SRSVs containing Bristol, Lordsdale, Toronto, OTH-25,
      Mexico, and Hawaii viruses. The amino acid identities between Camberwell and
      Bristol viruses for proteins encoded by ORF1 (partial), ORF2, and ORF3 were 99%,
      98%, and 90%, respectively. A highly variable region in ORF3 corresponding to
      amino acid residues 123 to 169 (Bristol and Camberwell numbering) were
      identified. Short segments of ORF1 (polymerase region) and the highly variable
      ORF3 region was analysed for the other four viruses. The results obtained
      indicated the potential usefulness of the variable region in distinguishing
      between closely related viruses.

PMID- 8732864
TI  - Determination of the inactivation kinetics of hepatitis A virus in human plasma
      products using a simple TCID50 assay.
AB  - The transmission of hepatitis A virus (HAV) associated with use of FVIII
      concentrates has been reported in a number of European countries. All of these
      cases were associated with products inactivated by use of solvent detergent
      treatment. These reports have emphasized the necessity of evaluating virus
      inactivation methodologies for their ability to inactivate HAV. Such studies had
      previously been hampered by the difficulties associated with titration of HAV,
      because of the minimal cytopathic effect of most strains of virus on tissue
      culture cells. We have developed a simple, rapid, TCID50 virus titration system
      using a cytopathic strain of HAV which allows extensive kinetic studies of HAV
      inactivation. This has been compared with the standard radioimmunofocus forming
      (RFF) assay which is presently used for HAV titration. The reproducibility of the
      TCID50 assay was demonstrated to be equal to that of the RFF assay and the 95%
      confidence intervals for titres determined by both assays were also equal. The
      thermal stability of the cytopathic strain was studied and shown to be equivalent
      to that of a noncytopathic strain. The kinetics of HAV inactivation by heating in
      aqueous solution were compared to those of HIV-1 and a number of model viruses.
      It was demonstrated that HAV was highly stable, with 5 hours heat treatment at 60
      degrees C in aqueous solution being required to inactivate 5.8 log10 virus. In
      contrast to heating in aqueous solution, lyophilization followed by 1 hour vapor
      heating at 60 degrees C was sufficient to inactivate 5.9 log10 HAV.

PMID- 8732865
TI  - Transcriptional expression of Epstein-Barr virus genes and proto-oncogenes in
      north African nasopharyngeal carcinoma.
AB  - Cases of nasopharyngeal carcinoma (NPC) from North Africa show an unusual bimodal
      age distribution. As elsewhere, the tumor is closely associated with the presence
      of Epstein-Barr virus (EBV). The expression of EBV genes and c-onc genes was
      studied in biopsy specimens from tumors at different clinical stages from 11
      young (10 to 30-year-old) and 11 adult (30 to 65-year-old) patients. It was found
      that the two age groups do not differ in their pattern of gene expression, that
      there is a tendency for later stage biopsies to express more viral and c-onc
      transcripts, and that samples expressing larger numbers of EBV genes also tend to
      express many different c-onc specificities.

PMID- 8732866
TI  - Molecular analysis of cellular loci disrupted by papillomavirus 16 integration in
      cervical cancer: frequent viral integration in topologically destabilized and
      transcriptionally active chromosomal regions.
AB  - To discern the structural features of cellular loci that are disrupted by type 16
      human papillomavirus (HPV-16) integration in cervical cancer, a polymerase chain
      reaction (PCR)-based strategy was employed for direct amplification and sequence
      analysis of four such cellular loci in cancer biopsy samples. One of the HPV-16
      disrupted loci was found to be the microtubule-associated protein (MAP-2) gene
      and the other three loci were uncharacterized and were designated PID-1 to -3
      (for papillomavirus integration-disrupted). The junctional sequences of the viral
      integration sites in the four loci analyzed are bracketed by long tracts of
      homogeneous purine or pyrimidine or alternating purine-pyrimidine which are known
      to destabilize the B-form conformation of the DNA structure. Using a panel of
      human/hamster hybrid cell DNAs and PCR analysis, the four loci were assigned to
      chromosomes 2 (MAP-2), 9 (PID-1), 1 (PID-2) and 8 (PID-3), respectively. These
      chromosomes carry numerous other previously determined viral integration and
      chromosomal fragile sites and the myc oncogenes. The PID-1 locus was further
      found in Southern analysis to be rearranged and amplified in another cervical
      cancer biopsy and a cervical carcinoma cell line (CaSki). On Northern analysis,
      the PID-1 and -3 probes detected a 3.0- and a 3.6-kb transcript, respectively, in
      normal cervical cells and in cervical cancer cell lines. The findings suggest
      that HPV-16 genome integrates frequently into topologically destabilized and
      transcriptionally active chromosomal sites. It remains to be elucidated whether
      the MAP-2 and the PID loci contribute to the pathogenesis of cervical cancer.

PMID- 8732867
TI  - Sensitive detection and quantification of particle-associated reverse
      transcriptase in plasma of HIV-1-infected individuals by the product-enhanced
      reverse transcriptase (PERT) assay.
AB  - Tests for the enzyme reverse transcriptase (RT) should permit the detection of
      all infectious retroviruses, provided that these are present as extracellular
      particles. The capability of a new procedure, named product-enhanced reverse
      transcriptase (PERT) assay, to detect HIV-1 in fresh human plasma was compared
      with that of the polymerase chain reaction (PCR) for viral RNA. Both procedures
      had identical dilution endpoints corresponding to 10(2) particles/ml. All 30
      samples from HIV-1 positive patients at different stages contained RT activity
      whose level was significantly correlated with viral RNA and corresponded to 553
      417,000 particles/ml. In HIV-1 low titer performance and seroconversion panels,
      the PERT assay detected more positives than PCR for viral RNA. Three of 160 blood
      donors exhibited elevated RT activity, indicating a prevalence of 1.9% (95% CI
      0.4-5.3%). One positive donor, with laboratory parameters suggesting a mild
      chronic liver impairment, exhibited RT activity comparable to that of HIV
      positives, but was consistently negative by various tests for hepatitis viruses,
      cytomegalovirus, the HIVs and HTLVs. The results suggest that the PERT assay is
      more sensitive for detection of HIV-1 contamination of plasma than RNA PCR.
      However, it is not affected adversely by viral sequence variability, and may
      therefore, also detect HIV-1 subtype O, and additional retroviruses as yet
      undetectable by PCR.

PMID- 8732868
TI  - Value of laboratory investigations in clinical suspicion of cytomegalovirus
      induced upper gastrointestinal tract ulcerations in HIV-infected patients.
AB  - To assess the value of laboratory investigations for the diagnosis and treatment
      of cytomegalovirus-induced upper gastrointestinal tract ulcerations, the medical
      records and biopsy material from HIV-infected patients were reviewed
      retrospectively during a 12-month period. Clinical diagnosis of cytomegalovirus
      (CMV) ulceration, based on characteristic endoscopic appearance of extensive
      ulceration of the mid- to distal esophageal or gastric mucosa and responsiveness
      to anti-CMV therapy, was compared with laboratory investigations of biopsies.
      Laboratory procedures consisted of both histopathological examination of the
      biopsy specimens and viral culture. Twenty episodes in 12 HIV-infected patients
      could be evaluated. Clinical diagnosis of CMV ulceration appeared to be justified
      in 14 of 20 episodes (70%), which were confirmed by laboratory investigations. Of
      the remaining six episodes, which showed partial or no response to anti-CMV
      therapy, laboratory investigations were negative in two episodes and discrepant
      in four episodes (histopathology or viral culture positive). A good response to
      anti-CMV therapy was more frequent in patients whose biopsies proved positive by
      histopathological examination and/or viral culture than in patients with negative
      tests (82% versus 0%), which indicates the importance of both investigations. In
      conclusion, laboratory diagnosis of CMV-induced upper gastrointestinal tract
      ulcerations supported the diagnosis and decisions on treatment of CMV-induced
      upper gastrointestinal tract ulcerations.

PMID- 8732870
TI  - A new drug to treat spasticity?

PMID- 8732869
TI  - Human herpesvirus 6 induces IL-8 gene expression in human hepatoma cell line, Hep
      G2.
AB  - The infectivity of human herpesvirus 6 (HHV-6) in a human hepatoma cell line, Hep
      G2 cells, and the effect of HHV-6 on production of inflammatory cytokines in
      these cells were examined to analyze pathogenesis of HHV-6 in the liver. We
      demonstrated that Hep G2 cells were susceptible to infection with HHV-6, and
      produced infectious virus. Moreover, infection of Hep G2 cells by HHV-6 induced
      the expression of IL-8 mRNA, but not IL-1 beta. The effect on induction of IL-8
      gene expression was observed only in Hep G2 cells infected with infectious virus,
      whereas both heat-inactivated HHV-6 and UV-irradiated HHV-6 did not change the IL
      8 mRNA level in these cells. These data suggest that HHV-6 may induce the
      cytokine-mediated inflammatory response by infecting liver cells, which could
      result in liver dysfunction in vivo.

PMID- 8732871
TI  - The superimposed effects of chronic phrenicotomy and cervical spinal cord
      hemisection on glial cytoarchitecture in the rat phrenic nucleus.
AB  - This study was conducted to determine the effects of chronic phrenicotomy on
      spinal hemisection-induced morphological plasticity occurring in the phrenic
      nucleus. Young adult rats were divided into a hemisection-alone and two
      hemisection-plus-phrenicotomy (HPP) groups. HPP animals received a left
      phrenicotomy two or four weeks prior to sacrificing; whereas hemisection-alone
      animals did not. All animals received a left C2 spinal hemisection 24 hours prior
      to death. Quantitative morphometric analysis of the phrenic nucleus showed
      significant reductions in phrenic dendritic size and the number of
      dendrodendritic appositions in HPP (two week) animals and in the length of
      dendrodendritic appositions in HPP (four week) animals. Significant increases in
      microglial area fraction in HPP (two week) animals and in astroglia area fraction
      in HPP (four week) animals were also detected. The results suggest that the
      alterations in the spinal hemisection-induced dendrodendritic apposition
      formation is most likely influenced by the different stages of the glial
      reactions induced by the chronic phrenicotomy/spinal hemisection.

PMID- 8732872
TI  - Prevalence of viral hepatitis B in an urban veteran spinal cord injured
      population.
AB  - The objective of this study was to determine the prevalence of viral hepatitis B
      (HBV) seropositivity in an urban veteran population with spinal cord injury (SCI)
      and the relationship of liver function test (LFT) values to HBV seropositivity.
      Eighty patients with chronic SCI (44 inpatients and 36 outpatients) had liver
      function tests (LFTs), hepatitis B surface antigen (HBsAg), hepatitis B surface
      antibody (anti-HBsAb) and hepatitis B core antibody (anti-HBcAb) evaluated.
      Seventy-seven able-bodied (non-SCI) outpatients without known viral hepatitis
      risk factors served as an urban veteran reference group. Results demonstrated a
      high prevalence of seropositivity for HBV in both veteran groups (SCI = 29
      percent; non-SCI = 22 percent). Subdividing the SCI group by inpatients and
      outpatients, HBV positivity was found to be significantly higher in the SCI
      inpatients than in either the SCI outpatient (39 percent vs 17 percent, x2 =
      4.67, p < 0.05) or non-SCI groups (39 percent vs 22 percent, x2 = 3.80, p =
      0.05). For the whole group, the gamma-glutamyl transpeptidase (GGT) level was
      greater in the HBV seropositive (n = 40) compared with the HBV seronegative (n =
      117) populations (82 +/- 17 vs 46 +/- 7 U/L, p = 0.019, respectively). In
      addition, the subgroup of spinal cord patients seropositive for hepatitis B (n =
      23) had a higher mean GGT than their seronegative (n = 57) counterparts (101 +/-
      26 vs 47 +/- 9 U/L, p = 0.018, respectively). We conclude that urban veterans in
      general, and especially those inpatients with SCI, may be at increased risk of
      HBV infection. An HBV vaccination program for veteran patients with SCI may be
      warranted.

PMID- 8732873
TI  - Problem solving and coping strategies in persons with spinal cord injury who have
      and do not have a family history of alcoholism.
AB  - Recovery from spinal cord injury (SCI) requires substantial coping by the
      patient. The coping process reflects both physical adjustment to permanent
      biological changes and psychological acceptance of these changes and their
      limitations to function. A history of family alcoholism appears as one prominent
      factor in persons with SCI. This factor is associated with several personality
      characteristics that could directly influence adjustment to the injury. As an
      initial exploration of this premise, the present study examined the relationship
      between family history of alcoholism and coping processes in SCI patients. Ninety
      volunteer subjects were selected from inpatient and outpatient populations of a
      Veterans Affairs spinal cord injury service. Based on structured interviews and
      responses to a standardized questionnaire, one group of 45 subjects, designated
      Family History Positive (FHP), were from families in which the father and at
      least one other second generation relative were alcoholics. The 45 Family History
      Negative (FHN) subjects were from families with no alcoholism subjects were from
      families with no alcoholism history. Once assigned to a group, subjects completed
      the Ways of Coping Questionnaire. Compared to subjects with no family alcoholism
      history, FHP subjects reported significantly more use of constructive coping
      strategies as measured by the Ways of Coping Questionnaire, but their alcohol use
      and anti-social behaviors indicated that they were less effective in actual
      coping behaviors. Persons with SCI and a family history of alcoholism reported
      utilization of coping methods that differ from those used by patients with SCI
      and no family alcoholism history. From the perspective of treatment and
      rehabilitation, this finding suggests the need to consider different therapeutic
      approaches for these groups.

PMID- 8732874
TI  - Ambulation in spinal cord injured patients--options: where do we stand?

PMID- 8732875
TI  - Functional prognosis of spinal cord injuries.

PMID- 8732876
TI  - Principles underlying functional electrical stimulation techniques.

PMID- 8732877
TI  - Orthotic prescription principles.

PMID- 8732878
TI  - Functional neuromuscular stimulation for mobility in people with spinal cord
      injuries. The Parastep I System.

PMID- 8732879
TI  - Limitations and inconsistencies in the approaches to cancer prevention.

PMID- 8732880
TI  - Chronic feeding study of deoxynivalenol in B6C3F1 male and female mice.
AB  - A 2 year feeding study was conducted with male and female B6C3F1 mice that
      consumed diets containing 0, 1, 5, or 10 ppm deoxynivalenol (DON). Survivability
      was good and, while the test animals gained less weight with increasing levels of
      DON in the diet, there were no consistent toxic manifestations associated with
      DON consumption. There was some evidence for an increase in serum IgA and IgG in
      females, and there were sporadic changes noted in the clinical chemistry and
      hematology parameters conducted at the terminal sacrifice. However, these changes
      were not considered to be biologically significant. The pathology results
      provided statistically significant dose-related evidence for a decrease in liver
      preneoplastic and neoplastic lesions as the dose level of DON increased. This
      negative trend probably results from the known positive correlation between body
      weight and the appearance of spontaneous hepatic neoplasms in this strain of
      mouse.

PMID- 8732881
TI  - Lack of carcinogenicity of daminozide, alone or in combination with its
      contaminant 1,1-dimethylhydrazine, in a medium-term bioassay.
AB  - The carcinogenicity of daminozide (succinic acid-2,2-dimethylhydrazide; Alar), a
      plant growth regulator used primarily in apple orchards, has been the subject of
      recent investigations by several national and international organizations because
      of contradictory study results. The aim of the present study was to assess the
      carcinogenicity of daminozide alone and in combination with 1,1-dimethylhydrazine
      (UDMH), its major contaminant, in a novel medium-term bioassay in Fischer 344
      rats, the DEN-PH model. Rats were given diethylnitrosamine (DEN) at 200 mg/kg
      body weight intraperitoneally and then 2 weeks later were given daminozide at
      20,000 ppm or daminozide plus UDMH at 75, 150, or 300 ppm in the diet for 6 weeks
      and were then killed; all rats underwent a partial (two-thirds) hepatectomy (PH)
      at week 3. Hepatocarcinogenic potential was assessed by comparing the number and
      area of preneoplastic foci positive for the glutathione S-transferase placental
      form (GST-P+) in the liver of treated rats, with those in controls given DEN
      alone. Daminozide, UDMH, and the combination were not carcinogenic in this model.
      This novel medium-term bioassay for carcinogenicity is considered to be practical
      for the rapid evaluation of both agrochemical formulations and contaminants found
      in agrochemicals and other compounds.

PMID- 8732882
TI  - International safety assessment of pesticides: dithiocarbamate pesticides, ETU,
      and PTU--a review and update.
AB  - For the last 30 years the Joint FAO/WHO Meeting on Pesticide Residues (JMPR) has
      carried out toxicological evaluations and safety assessments of dithiocarbamate
      pesticides, continuously adjusting previous appraisals in the light of new data
      and advances in the understanding of the principles and mechanisms of toxic
      action of these compounds. The historical narrative of the evaluative process is
      followed by an account of the present international safety assessment status of
      the dithiocarbamate pesticides so far examined by the JMPR. They are ferbam,
      mancozeb, maneb, metiram, nabam, propineb, thiram, zineb, ziram, and the
      associated substances, ethylenethiourea (ETU) and propylenethiourea (PTU).

PMID- 8732883
TI  - Neoplastic transformation by quartz in the BALB/3T3/A31-1-1 cell line and the
      effects of associated minerals.
AB  - Quartz, the most common form of crystalline silica, was tested quantitatively for
      neoplastic transformation in the mouse embryo cell line, BALB/3T3/A31-1-1. Five
      quartz dust samples of respirable size [Min-U-Sil 5 (MQZ); hydrofluoric-acid
      etched MQZ (HFMQZ); Chinese standard quartz (CSQZ); DQ12; and F600] all induced
      significant levels of neoplastic transformation, showing dose-dependent increases
      in the frequency of morphologically transformed foci at lower tested doses and a
      plateau level of response at higher doses. The plateau levels reached by the five
      tested samples did not differ substantially (maximum transformation frequencies
      per 10(5) cells ranging from 53.2 for MQZ to 28.3 for HFMQZ). F600 had minimal
      cytotoxicity but transforming activity comparable to the other samples. Cells
      from all tested transformed foci, when injected s.c. in nude mice, grew as
      sarcomas. Cytogenetic analysis showed that all tested silica-transformed cell
      lines had acquired one to five additional marker chromosomes, of types not seen
      in untreated control lines, indicative of induced chromosomal translocations and
      amplification. Increased expression of one or more of five genes (p53, myc, H
      ras, K-ras, and abl) was observed in several quartz-transformed cell lines. No
      transforming activity was found for hematite and anatase (both nontoxic), and for
      rutile (more toxic than MQZ). Combined exposure (1:1 w/w per unit culture area)
      of each of these dusts with MQZ showed that hematite and anatase inhibited MQZ
      toxicity as well as transformation, whereas rutile markedly enhanced MQZ toxicity
      but not MQZ-induced transformation.

PMID- 8732884
TI  - Social skill deficits and learning disabilities: a meta-analysis.
AB  - Over the past 15 years, increased attention has been directed at social skills
      and their relationship to learning disabilities. Using the methods of meta
      analysis, this investigation explores the nature of social skill deficits among
      students with learning disabilities. Across 152 studies, quantitative synthesis
      shows that, on average, about 75% of students with learning disabilities manifest
      social skill deficits that distinguish them from comparison samples.
      Approximately the same level of group differentiation is found across different
      raters (teachers, peers, self) and across most dimensions of social competence.
      Although social skill deficits appear to be an integral part of the learning
      disability experience, a number of questions about the relationship between
      learning disability and social skill deficits remain unanswered. Until these
      questions are answered, social skill deficits are best viewed as one among many
      elements of the learning disability constellation, and no significant
      definitional changes related to social skill deficits appear warranted.

PMID- 8732885
TI  - The effects of auditory stimulation on the arithmetic performance of children
      with ADHD and nondisabled children.
AB  - This study evaluated the impact of extra-task stimulation on the academic task
      performance of children with attention-deficit/hyperactivity disorder (ADHD).
      Twenty boys with ADHD and 20 nondisabled boys worked on an arithmetic task during
      high stimulation (music), low stimulation (speech), and no stimulation (silence).
      The music "distractors" were individualized for each child, and the arithmetic
      problems were at each child's ability level. A significant Group x Condition
      interaction was found for number of correct answers. Specifically, the
      nondisabled youngsters performed similarly under all three auditory conditions.
      In contrast, the children with ADHD did significantly better under the music
      condition than speech or silence conditions. However, a significant Group x Order
      interaction indicated that arithmetic performance was enhanced only for those
      children with ADHD who received music as the first condition. The facilitative
      effects of salient auditory stimulation on the arithmetic performance of the
      children with ADHD provide some support for the underarousal/optimal stimulation
      theory of ADHD.

PMID- 8732886
TI  - An examination of youth with attention-deficit/hyperactivity disorder and
      language learning disabilities: a clinical study.
AB  - This study examined the performance of 96 youth hospitalized at an acute-care
      psychiatric hospital on a battery of language measures. The participants were
      separated into four groups: (a) participants with language learning disabilities
      (LLD; n = 14), (b) participants with attention-deficit/hyperactivity disorder
      (ADHD; n = 26), (c) participants with both ADHD and LLD (ADHD/LLD; n = 18), (d)
      participants with neither ADHD nor LLD (Neither; n = 38). Participants with
      ADHD/LLD performed significantly more poorly than did the ADHD group or the
      Neither group on measures of phonology and syntax, but not semantics. However,
      participants with ADHD/LLD did not significantly differ from participants with
      LLD on a majority of language-based measures. This finding suggests that
      participants with ADHD/LLD have profiles more similar to those of participants
      with LLD than participants with ADHD. Educational implications for instruction
      for students with ADHD/LLD are presented.

PMID- 8732887
TI  - Factors that influence phoneme-grapheme correspondence learning.
AB  - The present study examined (a) the relative impact visual and phonetic factors
      have on learning phoneme-grapheme correspondences, and (b) the relationship
      between measures of visual and phonological processing and children's ability to
      learn novel phoneme-grapheme correspondence pairs. Participants were 20 children
      with reading disabilities (RD), 10 normally achieving children matched for mental
      age (MA), and 10 children matched for reading age (RA). The children ranged in
      age from 5 years 2 months to 9 years 3 months. All children completed a phoneme
      grapheme learning task consisting of four novel correspondence pairs, a visual
      processing task, and five measures of phonological processing. The MA and RA
      groups learned the four correspondence pairs in significantly fewer trials than
      the RD group. The RD group had the least difficulty learning the correspondence
      pair with different phonemes and graphemes and the most difficulty learning the
      correspondence pair with similar phonemes and graphemes. Performance on the
      learning task was significantly correlated to performance on the visual
      processing task and the five measures of phonological processing. Performance on
      the phonological processing task of short-term memory was the best predictor of
      overall performance on the learning task. Although children with RD were able to
      learn the four novel correspondence pairs, their processing deficiencies affected
      how readily they learned each of the correspondence pairs.

PMID- 8732888
TI  - Bimodal reading: benefits of a talking computer for average and less skilled
      readers.
AB  - Studies have shown that when information is presented through visual and auditory
      channels simultaneously (i.e., bimodal presentation), speed of processing and
      memory recall are enhanced. The present study demonstrated the efficacy of a
      bimodal approach to fostering reading comprehension. Eighteen average readers (9
      girls and 9 boys) and 18 less skilled readers (8 girls and 10 boys) in Grades 8
      and 9 participated in the study. Students were presented with social studies and
      science passages via a computer. Passages were presented in three conditions:
      visually (on screen), auditorily (read by digitized voice), and bimodally (on
      screen, highlighted, while being voiced). Following each passage, students
      answered 10 oral-response, short-answer comprehension questions. Results
      indicated that less skilled readers comprehended more with bimodal versus
      unimodal presentations. Overall, their performance in the bimodal condition was
      commensurate with average readers' comprehension in the visual condition. For
      less skilled readers, an increase in word recognition from pre- to posttesting on
      word lists was found across conditions. In addition, results of a brief consumer
      satisfaction survey suggested that low-skilled readers felt most successful in
      terms of their comprehension when passages were presented bimodally. Several
      clinical issues involved in presenting information bimodally using computers are
      discussed.

PMID- 8732889
TI  - The experiences of families of children with learning disabilities: parental
      stress, family functioning, and sibling self-concept.
AB  - Quantitative and qualitative measures of 19 parents and 19 siblings of school-age
      children with learning disabilities (a parent-sibling pair for each child) showed
      that the functioning of the families and the self-concept of the siblings were
      comparable to that in families of nondisabled children, but the parents in the
      former group experienced greater stress than did parents of nondisabled children.
      Furthermore, despite few problems in sibling relationships, the families
      experienced adaptational difficulties, especially with regard to the school.
      Family intervention and future research are suggested.

PMID- 8732890
TI  - Coping with school stress: a comparison of adolescents with and without learning
      disabilities.
AB  - The experience of school-related stress during the transition to junior high
      school is compared in a sample of 59 students with learning disabilities (27
      females, 32 males) and 402 students without learning disabilities (241 females,
      161 males). Using a checklist of 11 stressful school events, the authors found
      that adolescents with learning disabilities were more likely to report that they
      had failed a class and less likely to report they had been chosen for a school
      activity than their non-learning disabled peers. However, the two groups of
      students did not differ in their perceived stressfulness of any of the pertinent
      school events. Students with learning disabilities reported relying on cognitive
      avoidance as a coping strategy more heavily than did non-learning disabled
      students when coping with an academic stress event, and reported that they
      mobilized fewer peers for social support when dealing with an academic stressor
      or with an interpersonal problem. The implications of these differences for the
      students' well-being are discussed. It is also suggested that school policies
      need to be examined for their impact on the opportunity for students with special
      needs to form supportive peer relations within the school environment.

PMID- 8732891
TI  - An investigation of documentation submitted by university students to verify
      their learning disabilities.
AB  - To become eligible for support services at the postsecondary level, students with
      learning disabilities (LD) must submit documentation to verify the existence of a
      specific LD. The documentation submitted over a 5-year period by 415 students to
      a large public research university that offers a comprehensive program for
      students with LD was examined. An analysis of the documentation indicates that
      serious problems exist in the type and quality of evaluation reports. Problems
      include flaws in the comprehensiveness of the assessments, and the use of
      questionable instruments for this population. Recommendations for establishing
      guidelines for acceptable documentation are offered.

PMID- 8732892
TI  - Diagnostic utility of the WISC-III developmental index as a predictor of learning
      disabilities.
AB  - Wechsler's Deterioration Index (WDI) was developed as an indicator of cognitive
      impairment in adults but has been applied to children, because neuropsychological
      deficits have often been hypothesized to account for learning difficulties during
      the development period. Renamed the Wechsler Developmental Index, this measure
      has been used to discriminate among groups of children with and without learning
      disabilities. The present study replicated those findings with the Wechsler
      Intelligence Scale for Children-Third Edition, but also applied more appropriate
      diagnostic efficiency statistics to analyze the actual diagnostic utility of the
      WDI. These analyses revealed that the WDI performed at chance levels when
      distinguishing 611 students diagnosed with learning disabilities from those
      diagnosed with emotional disabled (n = 80) or mental retardation (n = 33), as
      well as from 2,200 simulated random nondisabled cases. It was concluded that mean
      group differences were not adequate and that ipsative indicators must be
      definitively validated in experimental environments before they can be applied in
      practice.

PMID- 8732893
TI  - Research designs and statistical techniques used in the Journal of Learning
      Disabilities, 1989-1993.
AB  - One hundred seventy-four research articles published in the Journal of Learning
      Disabilities from 1989 through 1993 were analyzed and coded by the type of
      research design and statistical technique used. Eighty percent of the research
      designs employed were identified as nonintervention methods. Fifty-five percent
      of all statistical techniques in the research articles reviewed were coded as
      primary, 32% were found to be intermediate, and the remaining 14% were considered
      advanced. The most frequently reported designs and analyses were those that are
      typically taught in most introductory and intermediate courses in research
      methods and statistics. Thus, the study indicates that readers would need at
      least a strong conceptual understanding of basic and intermediate statistical
      procedures to interpret research reported in the Journal of Learning
      Disabilities.

PMID- 8732894
TI  - Research in self-monitoring with students with learning disabilities: the
      present, the prospects, the pitfalls.
AB  - The amount of research in the use of self-monitoring intervention with students
      has increased steadily. This article reviews the literature to date on self
      monitoring with students with learning disabilities. First, it discusses the
      results of self-monitoring studies in terms of major dependent measures, such as
      on-task behavior and academic productivity and accuracy. Next, it analyzes
      studies comparing the effects of self-monitoring of attention and self-monitoring
      of performance on on-task behavior and academic responding. Finally, it discusses
      areas for future research and potential conceptual pitfalls.

PMID- 8732895
TI  - Vitamin E supplementation in cystic fibrosis.
AB  - Vitamin E is an antioxidant and may have a role in the protection of lung tissue
      against oxidative damage in cystic fibrosis. Previous studies of vitamin E status
      in cystic fibrosis have used plasma or serum concentrations, which vary with
      levels of carrier lipoproteins and hence may not reflect the concentration of
      vitamin E in tissues, where it is found in highest concentration in membranes.
      Erythrocyte vitamin E concentration has been shown to correlate well with tissue
      concentrations of the vitamin in animals, but it has not previously been studied
      in patients with cystic fibrosis. Current guidelines on vitamin supplementation
      in cystic fibrosis include vitamin E. It is not presently clear which level of
      supplementation is most appropriate. To address this question, we examined the
      effect on erythrocyte vitamin E levels of supplementation with either 15 mg or
      100 mg per day of vitamin E. Analysis was performed by high performance liquid
      chromatography before and 1 year after initiation of supplementation in children
      with cystic fibrosis. Erythrocyte vitamin E concentrations were below the normal
      range in almost all unsupplemented patients and rose into the normal range with a
      supplement of 100 mg per day, but not 15 mg per day. This rise was not accounted
      for by changes in general dietary treatment. We conclude that tissue vitamin E
      levels are low in patients with cystic fibrosis who do not receive supplements
      but can be normalized in most children with 100 mg of vitamin E. per day.

PMID- 8732896
TI  - Treatment of chronic enteritis in glycogen storage disease type IB with
      granulocyte colony-stimulating factor.

PMID- 8732897
TI  - Neural cell adhesion molecule (NCAM) expression in nerves and muscle of
      developing human large bowel.
AB  - Most studies of neural cell adhesion molecule (NCAM) in human musculature are
      devoted to either developing or adult skeletal and cardiac muscle. The aim of
      this study was to determine the pattern of NCAM expression in the intestinal
      musculature of the developing human large bowel. In specimens of large bowel from
      foetuses (gestational age 8-20 weeks), we examined the immunohistochemical
      localisation of NCAM in parallel to those of alpha-smooth muscle actin and
      desmin. Within the developing neural complex, NCAM was expressed at all stages
      investigated. In intestinal muscle at 8 weeks, immunoreactivity for all antisera
      was restricted to the muscularis propria. The differentiating muscularis mucosae
      was demonstrated first at 15 weeks by immunostaining for alpha-smooth muscle
      actin, and this expression was followed by that of NCAM and desmin at 17 and 19
      weeks, respectively. At 20 weeks, NCAM immunoreactivity in the external muscle
      was intense at the inner border of the circular muscle, with its concentration
      decreasing towards the outer margin of the muscular wall, whereas alpha-smooth
      muscle actin and desmin were uniformly distributed in all muscle layers. NCAM is
      expressed by nerves and muscle of developing human large intestine. Its
      appearance follows a predetermined pattern, which implies its relevance to the
      differentiation of intestinal muscle layers.

PMID- 8732898
TI  - Iron deficiency and intestinal malabsorption in HIV disease.
AB  - Children with human immunodeficiency virus (HIV) infection have a higher
      prevalence of intestinal malabsorption. Anemia is also a common feature in these
      children. The aims of this work were (a) to establish the prevalence of iron
      deficiency in HIV-infected children, (b) to test the hypothesis that iron
      deficiency is related to intestinal malabsorption, (c) to see whether it may
      contribute to anemia, and (d) to evaluate the sensitivity of oral iron load in
      the investigation of intestinal function. To accomplish these goals, 71 HIV
      infected symptomatic children were enrolled. Iron serum values were determined
      before and after oral load with ferrous sulfate. The correlation between basal
      and post-load iron levels was evaluated by linear regression. Xylose level after
      oral load, fecal fat, and fecal alpha 1-antitrypsin concentration were also
      determined. Iron deficiency was detected in 48% of patients, and it was
      significantly associated with intestinal iron malabsorption. Sugar malabsorption,
      steatorrhea, and fecal protein loss were detected in 26, 36, and 17% of patients,
      respectively. Low hemoglobin levels were detected in 66% of patients. The
      majority of children with iron deficiency also had anemia. Preliminary data
      showed that oral iron administration was sufficient for raising hemoglobin in
      children with normal iron absorption, whereas parenteral administration was
      required in those with iron malabsorption. We conclude that (a) iron deficiency
      is a major feature of pediatric HIV infection, (b) it is related to intestinal
      malabsorption, and (c) it contributes to anemia. Finally, oral iron load is a
      sensitive test for investigating intestinal function.

PMID- 8732899
TI  - Cysteine supplementation increases glutathione, but not polyamine, concentrations
      of the small intestine and colon of parenterally fed newborn rabbits.
AB  - The glutathione precursor cysteine is not contained in most total parenteral
      nutrition (TPN) formulations, and premature infants may not be capable of
      synthesizing cysteine because of a deficiency of cystathionase. Glutathione
      depletion may have negative effects on host defense against oxidative damage.
      Several studies have suggested that glutathione depletion induces ornithine
      decarboxylase activity and increases in polyamine concentrations. Since an
      inverse relationship between polyamine and glutathione concentrations has been
      suggested, the concentrations of both of these compounds may be altered in
      premature infants receiving TPN. We measured glutathione and polyamine
      concentrations of the small intestine and colon of prematurely delivered newborn
      rabbits administered TPN for 7 days after birth with or without added cysteine
      (75 or 150 mg kg-1 day-1). Maternally reared kits were also studied. Total
      glutathione concentrations in the gastrointestinal tract were significantly lower
      in kits administered cysteine-free TPN than in kits receiving cysteine or who
      were maternally reared. Polyamine concentrations did not differ among groups.
      Glutathione depletion of the small intestine and colon does occur during cysteine
      free parenteral nutrition and may compromise intestinal defense against oxidant
      damage.

PMID- 8732900
TI  - Endoscopic assessment of the colonic response to corticosteroids in children with
      ulcerative colitis.
AB  - Twenty children with active ulcerative colitis were assessed before and after 8
      weeks of medical therapy with 5-aminosalicylic acid (5-ASA) derivatives and
      corticosteroids. Local therapy was given for distal disease (seven cases); other
      disease was treated with oral prednisolone (1-2 mg/kg/day, maximum 40 mg).
      Eighteen of the children showed a clinical improvement on therapy, and complete
      remission of clinical disease activity by 8 weeks was seen in 17 (85%). C
      reactive protein was elevated initially in 10 of 20 children and returned to
      normal posttreatment in all but one. Reassessment of the colon after treatment
      showed an improved endoscopic appearance in 15 and complete remission in eight
      (40%). Histological improvement was seen in 13, with full remission in only three
      (15%). In conclusion, remission of clinical disease activity by corticosteroid
      therapy in ulcerative colitis may not be accompanied by endoscopic remission and
      uncommonly by mucosal healing. This finding may be important prognostically
      because of the risk of dysplasia in long-standing persistent mucosal
      inflammation.

PMID- 8732901
TI  - Cryptogenic hepatitis masking the diagnosis of ornithine transcarbamylase
      deficiency.
AB  - We describe three children with transaminase elevations and hepatic insufficiency
      who were given the diagnosis of cryptogenic hepatitis after the more common viral
      and metabolic diseases of the liver had been excluded. However, further
      laboratory investigations showed hyperammonemia, low blood urea levels, elevated
      plasma glutamine levels, and low citrulline levels. Urinary excretion of orotic
      acid was higher than normal, with absent urinary homocitrulline and normal
      fractional tubular reabsorption of lysine, ornithine, and arginine. These
      findings suggest the diagnosis of ornithine transcarbamylase deficiency. We
      emphasize the importance of investigating possible urea cycle disorders by
      determining ammonia plasma levels, both at baseline and after a protein load;
      urinary and plasma amino acids; and urinary orotic acid in all patients with
      liver disease of indeterminate etiology.

PMID- 8732902
TI  - Crohn's disease presenting as chronic pancreatitis with biliary tract
      obstruction.

PMID- 8732903
TI  - Severe gastrointestinal bleeding following liver transplantation in young
      children.

PMID- 8732904
TI  - Benign noninflammatory stricture of the common hepatic duct.

PMID- 8732905
TI  - Intestinal neuronal dysplasia in twins.
AB  - Intestinal neuronal dysplasia (IND) has been described proximal to the
      aganglionic segment in Hirschsprung's disease and less frequently as an isolated
      condition. Familial occurrence of IND is rare. We report a case of monozygotic
      twins affected with IND. One-year-old male monozygotic twins presented with a
      history of chronic constipation and abdominal distension since birth. At
      presentation, both twins had fecal impaction with palpable fecal-filled loops of
      bowel. Barium enema in both patients showed gross fecal loading of the sigmoid
      colon and rectum. Delayed films taken at 48 h showed marked barium retention.
      Suction rectal biopsy specimens examined by acetylcholinesterase (AChE)
      histochemistry in both patients showed moderately increased AChE-positive nerve
      fibers in the lamina propria, muscularis mucosae, and around submucosal blood
      vessels, as well as hyperplasia of submucous plexus with formation of giant
      ganglia. Both children underwent extended internal sphincter myectomy. Six months
      later, both patients had normal bowel function. The occurrence of IND in twins
      suggests that genetic factors are involved in the etiology of this disease.

PMID- 8732906
TI  - Impact of early discharge on newborns.

PMID- 8732907
TI  - Combined bowel-liver transplantation in an infant with microvillous inclusion
      disease.

PMID- 8732908
TI  - Different methods to analyze clinical experiments with multiple endpoints: a
      comparison of real data.
AB  - In many clinical experiments multiple measurements are required for evaluation of
      the results. Several methods have been illustrated in the literature to deal with
      this problem. Some of these solve the problem of multiple testing bias just by
      looking at the significance of the most pronounced difference. On the other hand,
      some other methods are designed to take into account all the information
      available from an experiment. The purpose of this paper is to review these
      methods and compare the results they gave when applied to a clinical trial in
      which drug efficacy was assessed by 14 outcome measures.

PMID- 8732909
TI  - Using the proportional odds model to assess the relationship between a multi-item
      and a global item efficacy scale in a psychiatric clinical trial.
AB  - The proportional odds model is illustrated in the analysis of two efficacy scales
      used in a phase II clinical trial involving 81 schizophrenic patients. The
      proportional odds model preserves the discrete, ordinal nature of one of the
      scales. The analysis of this data suggested that the relationship between the two
      scales is not captured by a linear proportional odds model. A linear model and a
      piecewise linear model for the explanatory variable were therefore compared using
      likelihood-based analyses. Residuals from both models were compared. Predicted
      probabilities for the ordinal categories were constructed from the estimated
      model. Extensions and limitations of the model for interpretation of other trials
      and for the planning of future trials are discussed.

PMID- 8732910
TI  - Generalized estimating equations for multivariate response with the variates
      having different distributions.
AB  - This paper addresses the problem of analyzing multivariate response with the
      variates having different distributions. We use the generalized estimating
      equations proposed by Prentice and Zhao (1) to estimate mean and covariance
      parameters. Wald statistics are used to test hypotheses about the parameters.
      Data from a two-group study of competing programs to increase memory recall in
      geriatric patients are analyzed. We are interested in determining whether there
      is a simultaneous increase in test scores with one variate being continuous and
      another being dichotomous. In a second example, comparisons of before-and-after
      treatment serum cholesterol levels and number of snacks eaten per day are made in
      an experiment to determine efficacy of a program aimed at simultaneously reducing
      both measurements.

PMID- 8732911
TI  - Sample sizes for experiments with multivariate repeated measures.
AB  - Procedures for determining sample size in multivariate repeated measures
      experiments are discussed. The focus is on designs with either one group or two
      independent groups of subjects, the point of departure being multivariate
      repeated measures. Determination of the minimum sample size required is based on
      power considerations associated with Hotelling's T2 and the F-test. We first
      consider procedures for determining sample size assuming an arbitrary covariance
      matrix. The special case where we assume that the transformed data have a
      multivariate spherical covariance matrix is also considered. Tables of the
      minimum sample sizes required for several hypotheses from multivariate analysis
      are presented.

PMID- 8732912
TI  - More on the means comparison with unequal variances problem.
AB  - Scheffe gave an exact solution to the problem of comparing two means from normal
      populations with unequal variances that is useful for general analysis of
      variance problems. The behavior of the usual t-statistic that assumes equal
      variances is contrasted to Satterthwaite's approximate t-statistic and Scheffe's
      method. An interesting relationship is uncovered between Scheffe's and
      Satterthwaite's solutions.

PMID- 8732913
TI  - Use of lattice square designs in bioassays.
AB  - The use of Lattice Square designs for estimating the relative potencies in a
      multiple bioassay is illustrated in this paper. The analysis is presented with
      and without recovery of inter-row and column information.

PMID- 8732914
TI  - Baseline balance and conditional size: a reply to Overall et al.
AB  - A previous paper in this journal mistakenly attributes a proposal to me that I
      did not make. I clear up the confusion. I also bring reasons to believe that the
      simulation presented in that paper is not relevant.

PMID- 8732915
TI  - Directional decision for a two-tailed alternative.

PMID- 8732916
TI  - Asbestos exposure and ovarian fiber burden.
AB  - Epidemiologic studies suggest increased risk of epithelial ovarian cancer in
      female asbestos workers and increased risk of malignancy in general in household
      contacts of asbestos workers. Ovaries were studied from 13 women with household
      contact with men with documented asbestos exposure and from 17 women undergoing
      incidental oophorectomy. Ovarian tissue was examined by analytic electron
      microscopy. Significant asbestos fiber burdens were detected in 9 out of 13 women
      with household asbestos exposure (69.2%), and in 6 out of 17 women who gave no
      exposure history (35%). Three exposed women had asbestos counts over 1 million
      fibers per gram wet weight (23%), but only 1/17 women without an exposure history
      had a count that high (6%). Although asbestos has been documented as a
      contaminant of some older cosmetic talc preparations, the chrysotile and
      crocidolite types of asbestos we detected are more indicative of background
      and/or occupational exposure. This study demonstrates that asbestos can reach the
      ovary. Although the number of subjects is small, asbestos appears to be present
      in ovarian tissue more frequently and in higher amounts in women with a
      documentable exposure history.

PMID- 8732917
TI  - Partition of circulating lead between serum and red cells is different for
      internal and external sources of lead.
AB  - Serum lead, whole blood lead, and lead in both tibia and calcaneus were measured
      in each of 49 active lead workers. Serum lead correlated more strongly with both
      in vivo bone lead measurements than did whole blood lead. The ratio of serum lead
      to whole blood lead varied from 0.8% to 2.5% and showed a positive correlation
      with tibia, and an even stronger correlation with calcaneus lead. This implies
      that lead released from bone (endogenous exposure) results in a higher proportion
      of whole blood lead being in serum than is the case for exogenous exposure. This
      observation needs to be confirmed, and the relationships amongst the parameters
      must be studied further, particularly in former or retired lead workers. If
      confirmed, since at least a portion of lead in serum is readily diffusible and
      thus toxicologically more immediately significant than lead bound to red cells,
      the health implications of endogenous exposure may have to be reassessed.

PMID- 8732918
TI  - A 25-year follow-up study of heavily exposed vinyl chloride workers in Germany.
AB  - The course of vinyl chloride-induced disease observed in 21 polyvinyl chloride
      (PVC) production workers, covering the period from first exposure to diagnosis
      and finally to death, and the difficulties in elucidating the true character of
      the lesions and their occupational origin are described. In 19 cases death was
      due to malignant hepatoma, predominantly angiosarcoma of the liver, but
      hepatocellular and cholangiocellular carcinoma were also found. Two workers died
      of complications of noncirrhotic portal fibrosis with portal hypertension. Except
      for the final stages, there was strikingly little impairment of hepatic function.
      Latency periods in workers with malignant hepatoma ranged from 12 to 34 years;
      mean latency was 22 years, and younger age at first exposure (here age < 27)
      seemed to have been accompanied by shorter latency periods.

PMID- 8732919
TI  - Respiratory health in asbestos-exposed ironworkers.
AB  - This study aimed to determine the prevalence of respiratory morbidity among
      asbestos-exposed ironworkers and to determine the relationship between
      respiratory morbidity indices and length of exposure. A medical screening
      provided information on chest radiographic abnormalities, pulmonary function,
      rales, finger clubbing, and respiratory symptoms for 547 asbestos-exposed
      ironworkers. Union pension records furnished data on length of exposure. The
      study group exhibited on increased prevalence of small irregular opacities,
      pleural plaques, and pleural thickening on chest x-ray; reduced FEF 25-75; rales;
      and respiratory symptoms. After controlling for the effect of cigarette smoking
      and age, years since joining the ironworkers union were significantly associated
      with profusion, pleural thickening, pleural plaques, rales, percent predicted
      FVC, reduced FVC, reduced FEV1, reduced FEV1/FVC, and dyspnea grades I, II, III,
      and IV.

PMID- 8732920
TI  - Humoral and cellular immune responses in asthmatic isocyanate workers: report of
      two cases.
AB  - Two workers (23 and 28 years old) developed rhinitis and bronchial asthma after
      occupational contact with the isocyanate MDI. Positive skin prick test results
      for MDI-HSA and IgE antibodies to all isocyanate-HSA conjugates were obtained in
      both cases, and the inhalation challenge test with MDI produced immediate and
      late asthmatic reactions. In the patch test and the stimulation assay of
      peripheral mononuclear blood cells, a specific sensitization to the diamine MDA
      (in both cases) and to further amines (in one case), as well as to hydrolysates
      of the respective diisocyanates, was seen, which appears to be independent of the
      IgE response to isocyanate-HSA conjugates. Our results offer evidence of IgE
      mediated, as well as lymphocyte, responses induced by exposures to isocyanate
      products over several months or years.

PMID- 8732921
TI  - Review of occupational lung carcinogens.
AB  - Lung cancer is the most common malignancy in the United States and is ranked
      second only to bladder cancer in the proportion of cases thought to be due to
      occupational exposures. We review the epidemiology of occupational lung cancer,
      focusing on agents identified as pulmonary carcinogens by the International
      Agency for Research on Cancer. We derive estimates of overall relative risks from
      the major studies of these lung carcinogens, and we also provide estimates of the
      number of exposed workers. Using our data as well as estimates from other
      authors, we estimate that approximately 9,000-10,000 men and 900-1,900 women
      develop lung cancer annually in the United States due to past exposure to
      occupational carcinogens. More than half of these lung cancers are due to
      asbestos. This estimate is likely conservative, in that we have restricted our
      analysis to confirmed lung carcinogens and have ignored occupations with
      documented excess risk but for which the specific agents are unknown. Also, our
      estimate of the proportion of workers exposed in the past is probably too low.
      Our estimate should be viewed only as broad approximation. Nevertheless, it is in
      line with other estimates by authors using different methods. The current number
      of cases estimated to be due to occupational exposure reflects past high
      exposures and is likely to drop in the future, unless other occupational lung
      carcinogens are confirmed or new carcinogens are introduced into the workplace.

PMID- 8732922
TI  - Risk of lung cancer among former chromium smelter workers.
AB  - Hexavalent chromium is a known carcinogen. Previous epidemiologic studies in the
      1950s of United States workers from seven facilities producing chromium compounds
      from chromite ore have reported a markedly increased risk for dying from lung
      cancer. As part of a high risk notification project of workers from four of these
      facilities, a mortality study was performed. The cohort was assembled in 1990
      1991 from the Social Security records of four former chromate producing
      facilities in northern New Jersey. The study subjects were known to have worked
      at these facilities some time between 1937 and 1971. Proportionate mortality and
      proportionate cancer mortality ratios (PCMR) were calculated. The overall risk
      for lung cancer was a PCMR of 1.51 (confidence limits [CL] 1.29-1.74) for white
      men and 1.34 (CL 1.00-1.75) for black men. These risks increased with increasing
      duration of employment and latency since time of first employment. The PCMR for
      greater than 20 years duration of work and more than 20 years since first
      exposure was 1.94 (CL 1.15-3.06) for white men and 3.08 (CL 1.13-6.71) for black
      men. The risk for lung cancer for white men remains elevated more than 20 years
      after exposure has ceased (PCMR, 1.29; CL 1.03-1.60). The PCMR for nasal
      cavity/sinus cancer was also found to be a significantly increased, 5.18 (CL 2.37
      11.30). A cluster of bladder cancer was seen among black workers from one
      facility, (PCMR, 3.30; CL 1.42-6.51). Despite the cessation of exposure, former
      chromium workers remain at significantly increased risk of lung cancer. Although
      there have been case reports of nasal cavity/ sinus cancer in association with
      chromium exposure, this is the first epidemiologic study to report a significant
      increase in these cancers. Limitations in this study include lack of exposure
      data and lack of information on smoking habits. The lack of increase in other
      smoking-related diseases besides lung cancer indicates that the increase in lung
      cancer cannot be attributed to cigarette smoking. The ongoing elevated risk of
      lung cancer after cessation of exposure emphasizes the need for developing early
      detection texts for lung cancer.

PMID- 8732923
TI  - Proportionate mortality study of golf course superintendents.
AB  - A proportionate mortality study of a cohort of golf course superintendents was
      conducted using death certificates for 686 deceased members of the Golf Course
      Superintendents Association of America who died from 1970 to 1992. White males
      were included in the study population from all 50 states. The study objective was
      to compare mortality from this cohort to the general U.S. white male population.
      The proportionate mortality ratio (PMR) for all types of cancer was 136 (CI: 121,
      152). Significant excess mortality from smoking-related diseases was observed.
      The PMR for arteriosclerotic heart disease was 140, which was significantly
      elevated (CI: 127, 155). In addition, the PMR for all respiratory diseases was
      176 (CI: 135,230), while the PMR for emphysema was 186 (CI: 101,342). The PMR for
      lung cancer was 117 (CI: 93, 148). Mortality for four cancer types--brain,
      lymphoma (non-Hodgkin's lymphoma, NHL), prostate, and large intestine--occurred
      at elevated levels within this cohort: brain cancer PMR = 234 (CI: 121,454), non
      Hodgkin's lymphoma (NHL) PMR = 237 (CI: 137,410), prostate cancer PMR = 293 (CI:
      187,460), and large intestine cancer PMR = 175 (CI: 125,245). The PMR for
      diseases of the nervous system was 202 (CI: 123,333). A similar pattern of
      elevated NHL, brain, and prostate cancer mortality along with excess deaths from
      diseases of the nervous system has been noted among other occupational cohorts
      exposed to pesticides.

PMID- 8732924
TI  - Take-home lead poisoning in a child from his father's occupational exposure.
AB  - With the publication of revised CDC guidelines in 1991, concern about childhood
      lead poisoning has increased. Exposure to lead-based paint and paint dust is
      currently considered the major source of lead poisoning in the United States. We
      describe a child who had elevated BLL related to lead-contaminated clothing that
      the father brought home from his workplace.

PMID- 8732925
TI  - Fall-related occupational injuries on farms.
AB  - We assessed risk factors for fall-related farm injuries in a population-based,
      case-control study. Cases had to reside in a defined geographic region served by
      a single medical center. Multiple sources reported cases, and a special farm
      census enabled random selection of controls, The annual risk of farm fall injury
      was 7.5 (95% CI: 5.7, 10.0) per 1,000 person-years. The crude incidence rate was
      higher in men, while the rate based on hours of farmwork was higher in women. In
      a multivariate analysis of risk factors, three factors were significantly
      associated with the risk. The risk of fall injury increased 2% (95% CI: 1%, 4%)
      per hour worked. Residents of farms with some farm workers not living on the farm
      had a fall injury rate 2.5 (95% CI: 1.0, 6.2) times greater than residents of
      other farms. Residents of farms with registered cows had one-third (95% CI: 0.14,
      0.93) the risk of residents of other farms. To identify environmental hazards for
      fall injuries, researchers from several disciplines may need to collaborate in
      the design and conduct of studies that include injury site investigations.

PMID- 8732926
TI  - Tradeswomen's perspectives on occupational health and safety: a qualitative
      investigation.
AB  - Qualitative research methods were used to determine the health and safety
      concerns of women employed in the construction trades. Major categories of
      concern were identified, including: 1) exposure to chemical and physical agents;
      2) injuries from lifting/bending/ twisting, falling, and lacerations; 3) lack of
      proper education and training; and 4) the health and safety risks related
      specifically to tradeswomen. Many of the issues identified by the workers are
      amenable to change through either engineering, behavioral, or administrative
      interventions.

PMID- 8732927
TI  - Can Dupuytren's contracture be work-related?: review of the evidence.
AB  - Dupuytren's contracture (DC) is a disease of the palmar fascia resulting in
      thickening and contracture of fibrous bands on the palmar surface of the hands
      and fingers. For decades, a controversy has existed regarding whether acute
      traumatic injury or cumulative biomechanical work exposure can contribute to the
      development of this disorder. To address this controversy, this review considers
      the following questions: Is there evidence that DC is associated with 1) frequent
      or repetitive manual work; and 2) hand vibration? The published literature was
      searched for studies meeting the following criteria: 1) in English or having an
      English abstract; 2) controlled studies; 3) DC an identified health outcome
      studied; and 4) the study group exposed to repetitive or frequent manual work,
      vibration, or acute traumatic injury. Relevant non-English articles identified
      through English abstracts were translated. The validity of studies meeting the
      selection criteria was assessed using a series of questions adapted from those of
      Stock [1991: Am J Ind Med 19:87-107]. Studies that met a priori minimum levels of
      methodologic quality were taken into account to reach conclusions with respect to
      the above questions. Odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated for each study. Ten studies met the initial selection criteria. Of
      these, four studies met the criteria for methodologic quality, one addressing the
      relationship between manual work and DC, and three studies of vibration and DC.
      No controlled studies of acute trauma and DC were identified. Bennett [1982: Br J
      Ind Med 39:98-100] found the prevalence of DC at a British PVC bagging and
      packing plant in which workers were exposed to repetitive manual work to be 5.5
      times that at a local plant without packing, and twice the expected prevalence in
      a U.K. working population previously studied by Early [1962: J Bone Joint Surg
      44B:602-613]. DC was observed more frequently among vibration white finger
      claimants than controls by Thomas and Clarke [1992: J Soc Occup Med 42:155-158]
      (OR, 2.1; 95% CI, 1.1-3-9), and more frequently among vibration-exposed workers
      than controls by Bovenzi et al. [1994: Occup Environ Med 51:603-611] (OR, 2.6 95%
      CI, 1.2-5.5). Cocco et al [1987: Med Lav 78:386-392] found that a history of
      vibration exposure occurred more frequently among cases of DC than among controls
      (OR, 2.3; 95% CI, 1.5-4.4). The latter two studies presented some evidence of a
      dose-response relationship. There is good support for an association between
      vibration exposure and DC.

PMID- 8732928
TI  - Silica and progressive systemic sclerosis (scleroderma): evidence for workers'
      compensation policy.
AB  - The occurrence of several confirmed cases of progressive systemic sclerosis
      (scleroderma) among male miners prompted a request by a member of the provincial
      parliament (MPP) of Ontario that the Industrial Disease Standards Panel (IDSP)
      evaluate the evidence for an occupational connection. A number of publications in
      reputable peer-reviewed medical journals offer case-control evidence gathered
      over four decades on three continents showing a rather clear-cut relationship
      between occupational exposure to crystalline silica and scleroderma. This article
      summarizes the evidence for a causal relationship and describes the process by
      which the members of the panel, using the criteria developed by Sir Austin
      Bradford Hill as a guide, made a finding of probable connection, the term
      mandated by the Workers' Compensation Act of Ontario. It provides insight into
      the difficulties encountered by those setting occupational disease policy when
      scientific certainty is unobtainable.

PMID- 8732929
TI  - Neurobehavioral test performance among apprentice painters: baseline data.
AB  - In the debate on chronic effects of solvent use, it is often difficult to find
      information on the cerebral health status of subjects before any exposure has
      occurred. The objective of this study was to obtain baseline data by examination
      of workers at the beginning of their occupational lives. This study compares the
      performance of 57 apprentice painters, mean age 16.6 +/- 1.2 years, with that of
      62 apprentices, mean age 16.2 +/- years, drawn from other manual trades involving
      no significant exposure to solvents. Their performances were compared twice over
      a period of 3 years using a series of behavioral tests chosen from a translated
      version of the Neurobehavioral Evaluation System (NES). There were no major
      differences in performance between the apprentices, except for the verbal ability
      test, which showed lower results for painters. This can be explained by factors
      such as socioeconomic background, previous schooling, or mother tongue, and
      raises the question of whether it is appropriate to use such a test to adjust for
      the influence of premorbid ability in elderly exposed workers.

PMID- 8732930
TI  - Decreases in postural change in finger blood flow in ceramic painters chronically
      exposed to low level lead.
AB  - To elucidate the effect of low level lead (Pb) exposure on somatic and autonomic
      peripheral nerve functions in ceramic painters, 58 males and 70 females, aged 29
      75 years (mean 53.3 years), with lead concentrations in blood (Pb-B) ranging from
      2.1 to 69.5 micrograms/dl (geometric mean 13.3 micrograms/dl), were examined for
      median nerve maximal conduction velocity as a measure of motor nerve function,
      the coefficient of variation of R-R interval on electrocardiography as a measure
      of parasympathetic function, and postural changes in finger blood flow volume
      (delta FBF), and changes in finger blood flow drop velocity (FDV) from the supine
      to standing position as a measure of sympathetic function. No significant
      association was found between Pb-B levels and the results of the
      neurophysiological tests, however, except for that between Pb-B and delta FBF was
      decreased linearly with increasing Pb-B levels. However, this association could
      not be concluded to be a reflection of sympathetic nerve dysfunction due to Pb
      exposure in the subjects, since delta FBF was not a specific parameter of
      sympathetic nerve function. The possibility that the decrease in delta FBF is a
      reflection of the atherosclerotic effect of chronic low level Pb exposure should
      be further investigated.

PMID- 8732931
TI  - Induction of micronuclei in cultured mammalian cells by fume condensates of
      roofing asphalt.
AB  - A considerable number of workers in the United States are employed in asphalt
      industries and are potentially exposed to asphalt fumes. The information
      regarding the potential carcinogenic hazards of such fumes to exposed workers is
      still limited. Studies have been conducted to determine the cytogenetic effects
      of roofing asphalt fume using cultured mammalian cells. Exponentially growing
      Chinese hamster lung fibroblasts (V79 cells) were exposed to different
      concentrations of condensates of type I and type III roofing asphalt fumes,
      generated at temperatures similar to actual roofing operation (316 +/- 10 degrees
      C). The frequencies of micronucleated cells in the treated and control cultures
      were determined. Additionally, immunofluorescent staining of kinetochore with
      human anti-kinetochore primary antibody and flouresceinated goat anti-human IgG
      was used to investigate the potential mechanism of micronucleus formation. The
      results show that both types of roofing asphalt fume condensates caused a
      significant increase in the frequency of micronucleated cells, and that 70% of
      micronucleated cells induced by asphalt fume condensates carried kinetochore
      positive micronuclei. These findings indicate that both type I and type III
      roofing asphalt fumes are capable of causing principally cytogenetic damage by
      spindle apparatus alterations in cultured mammalian cells.

PMID- 8732932
TI  - Serum perfluorooctanoic acid and hepatic enzymes, lipoproteins, and cholesterol:
      a study of occupationally exposed men.
AB  - Perfluorooctanoic acid (PFOA) produces marked hepatic effects, including
      hepatomegaly, focal hepatocyte necrosis, hypolipidemia, and alteration of hepatic
      lipid metabolism in a number of animal species. In rodents, PFOA is a peroxisome
      proliferator, an inducer of members of the cytochrome P450 superfamily and other
      enzymes involved in xenobiotic metabolism, an uncoupler of oxidative
      phosphorylation, and may not be a cancer promoter. Although PFOA is the major
      organofluorine compound found in humans, little information is available
      concerning human responses to PFOA exposure. This study of 115 occupationally
      exposed workers examined the cross-sectional associations between PFOA and
      hepatic enzymes, lipoproteins, and cholesterol. The findings indicate that there
      is no significant clinical hepatic toxicity at the PFOA levels observed in this
      study. PFOA may modulate the previously described hepatic responses to obesity
      and xenobiotics.

PMID- 8732933
TI  - Exposure determinants needed to improve the assessment of exposure.

PMID- 8732935
TI  - Delaney still the best protection.

PMID- 8732936
TI  - 1-Hydroxypyrene as an indicator of pyrene exposure.

PMID- 8732937
TI  - Radiation and childhood cancer.

PMID- 8732938
TI  - Regulatory reform proposals and the public health.
AB  - The U.S. Congress is considering legislation that would change policy for
      environmental health in important ways. Current approaches have been criticized
      for addressing the wrong set of priorities and consuming too many resources. The
      legislation requires additional analyses and sets new decision criteria to be
      applied to federal agency actions taken to protect the environment and public
      health. Close review of the legislation suggests that though it is intended to
      address identified problems, it is unlikely to lead to an improved basis for
      public policy and is likely to paralyze the regulatory process. Reform proposals
      that reduce rather than increase fragmentation of decision-making and that
      address problems comprehensively rather than selectively are needed.

PMID- 8732940
TI  - The environmental two-step.

PMID- 8732939
TI  - The Agricultural Health Study.
AB  - The Agricultural Health Study, a large prospective cohort study has been
      initiated in North Carolina and Iowa. The objectives of this study are to: 1)
      identify and quantify cancer risks among men, women, whites, and minorities
      associated with direct exposure to pesticides and other agricultural agents; 2)
      evaluate noncancer health risks including neurotoxicity reproductive effects,
      immunologic effects, nonmalignant respiratory disease, kidney disease, and growth
      and development among children; 3) evaluate disease risks among spouses and
      children of farmers that may arise from direct contact with pesticides and
      agricultural chemicals used in the home lawns and gardens, and from indirect
      contact, such as spray drift, laundering work clothes, or contaminated food or
      water; 4) assess current and past occupational and nonoccupational agricultural
      exposures using periodic interviews and environmental and biologic monitoring; 5)
      study the relationship between agricultural exposures, biomarkers of exposure,
      biologic effect, and genetic susceptibility factors relevant to carcinogenesis;
      and 6) identify and quantify cancer and other disease risks associated with
      lifestyle factors such as diet, cooking practices, physical activity, smoking and
      alcohol consumption, and hair dye use. In the first year of a 3-year enrollment
      period, 26,235 people have been enrolled in the study, including 19,776
      registered pesticide applicators and 6,459 spouses of registered farmer
      applicators. It is estimated that when the total cohort is assembled in 1997 it
      will include approximately 75,000 adult study subjects. Farmers, the largest
      group of registered pesticide applicators comprise 77% of the target population
      enrolled in the study. This experience compares favorably with enrollment rates
      of previous prospective studies.

PMID- 8732941
TI  - Turning brownfields green again.

PMID- 8732942
TI  - Biosphere 2's quest for credibility.

PMID- 8732943
TI  - Dangerous dental sealants?

PMID- 8732944
TI  - New center to study environmental impacts on reproductive risk.

PMID- 8732945
TI  - Phenolphthalein highlights NTP bioassay review.

PMID- 8732946
TI  - Ocean commotion.

PMID- 8732947
TI  - Vanishing biodiversity.

PMID- 8732948
TI  - Fat pharms.

PMID- 8732949
TI  - Pesticide appliers, biocides, and birth defects in rural Minnesota.
AB  - Earlier studies by our group suggested the possibility that offspring of
      pesticide appliers might have increased risks of birth anomalies. To evaluate
      this hypothesis, 935 births to 34,772 state-licensed, private pesticide appliers
      in Minnesota occurring between 1989 and 1992 were linked to the Minnesota state
      birth registry containing 210,723 live births in this timeframe. The birth defect
      rate for all birth anomalies was significantly increased in children born to
      private appliers. Specific birth defect categories, circulatory/respiratory,
      urogenital, and musculoskeletal/integumental, showed significant increases. For
      the general population and for appliers, the birth anomaly rate differed by corp
      growing region. Western Minnesota, a major wheat, sugar beet, and potato growing
      region, showed the highest rate of birth anomalies per/1000 live births: 30.0 for
      private appliers versus 26.9 for the general population of the same region. The
      lowest rates, 23.7/1000 for private appliers versus 18.3/1000 for the general
      population, occurred in noncorp regions. The highest frequency of use of
      chlorophenoxy herbicides and fungicides also occurred in western Minnesota.
      Births in the general population of western Minnesota showed a significant
      increase in birth anomalies in the same three birth anomaly categories as
      appliers and for central nervous system anomalies. This increase was most
      pronounced for infants conceived in the spring. The seasonal effect did not occur
      in other regions. The male/female sex ratio for the four birth anomaly categories
      of interest in areas of high phenoxy herbicide/fungicide use is 2.8 for appliers
      versus 1.5 for the general population of the same region (p = 0.05). In minimal
      use regions, this ratio is 2.1 for appliers versus 1.7 for the general
      population. The pattern of excess frequency of birth anomalies by pesticide use,
      season, and alteration of sex ratio suggests exposure-related effects in appliers
      and the general population of the crop-growing region of western Minnesota.

PMID- 8732951
TI  - Identification of anovulation and transient luteal function using a urinary
      pregnanediol-3-glucuronide ratio algorithm.
AB  - The sensitivity and specificity of a urinary pregnanediol-3-glucuronide (PdG)
      ratio algorithm to identify anovulatory cycles was studied prospectively in two
      independent populations of women. Urinary hormone data from the first group was
      used to develop the algorithm, and data from the second group was used for its
      validation. PdG ratios were calculated by a cycles method in which daily PdG
      concentrations indexed by creatinine (CR) from cycle day 11 onward were divided
      by a baseline PdG (average PdG/Cr concentration for cycle days 6-10). In the
      interval method, daily PdG/CR concentrations from day 1 onward were divided by
      baseline PdG (lowest 5-day average of PdG/CR values throughout the collection
      period). Evaluation of the first study population (n = 6) resulted in cycles with
      PdG ratios > or = 3 for > or = 3 consecutive days being classified as ovulatory;
      otherwise they were anovulatory. The sensitivity and specificity of the PdG ratio
      algorithm to identify anovulatory cycles in the second population were 75% and
      89.5%, respectively, for all cycles (n = 88); 50% and 88.3% for first cycles (n =
      40) using the cycles method; 75% and 92.2%, respectively, for all cycles (n =
      89); and 50% and 94.1% for first cycles (n = 40) using the interval method. The
      "gold standard" for anovulation was weekly serum samples < or = 2 ng/ml
      progesterone. The sensitivity values for all cycles and for the first cycle using
      both methods were underestimated because of apparent misclassification of cycles
      using serum progesterone due to infrequent blood collection. Blood collection
      more than once a week would have greatly improved the sensitivity and modestly
      improved the specificity of the algorithm. The PdG ratio algorithm provides an
      efficient approach for screening urine samples collected in epidemiologic studies
      of reproductive health in women.

PMID- 8732950
TI  - Scaling basic toxicokinetic parameters from rat to man.
AB  - Scaling of the quantified dispositional parameters of xenobiotics from animals to
      man is of interest from the standpoint of toxicology (e.g., poisoning and risk
      assessment). Scaling is also important from the standpoint of therapeutics
      because it represents a strategy for predicting first-use-in-human doses in
      clinical trials of investigational new drugs. Current strategies for scaling
      either doses of xenobiotics or the dispositional parameters of xenobiotics from
      animals to man rely on models that take account principally of species
      differences in weight or body surface area. Interspecies scaling of dispositional
      parameters such as clearance or volume of distribution commonly involves the
      comparison of estimates of these parameters for a given xenobiotic among numerous
      species on the basis of weight with the resultant mathematical relationship used
      to predict the values of those parameters for that xenobiotic in a species
      weighing, on average, about 70 kg (i.e., a man). Our approach has been to
      ascertain whether a useful mathematical model could be developed for predicting
      the dispositional parameters of a xenobiotic, its half-life and volume of
      distribution, in humans based exclusively on estimates of those parameters in
      rats. Based on a data set of about 100 different xenobiotics, we found that
      values for half-life and volume of distribution of a xenobiotic in humans can be
      predicted from the estimates of those parameters in rats.

PMID- 8732952
TI  - Synoptic weather modeling and estimates of the exposure-response relationship
      between daily mortality and particulate air pollution.
AB  - This study estimated the association between particulate air pollution and daily
      mortality in Utah Valley using the synoptic climatological approach to control
      for potential weather effects. This approach was compared with alternative
      weather modeling approaches. Although seasonality explained a significant amount
      of variability in mortality, other weather variables explained only a very small
      amount of additional variability in mortality. The synoptic climatological
      approach performed as well or slightly better than alternative approaches to
      controlling for weather. However, the estimated effect of particulate pollution
      on mortality was mostly unchanged or slightly larger when synoptic categories
      were used to control for weather. Furthermore, the shape of the estimated dose
      response relationship was similar when alternative approaches to controlling for
      weather were used. The associations between particulate pollution and daily
      mortality were not significantly different from a linear exposure-response
      relationship that extends throughout the full observed range of pollution.

PMID- 8732953
TI  - Persistence of decreased T-helper cell function in industrial workers 20 years
      after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - In experimentally exposed animals 2,3,7,8-tetrachlorodibenzo-n-dioxin (TCDD)
      causes severe immunosuppression. However, the overall susceptibility of humans
      for the different pathological effects of TCDD has remained unclear. We examined
      the long-term effects of TCDD in 11 industrial workers who were exposed to high
      doses of TCDD for several years 20 years ago. Current TCDD body burdens were
      still at least 10 times higher (between 43 and 874 pg/g blood far) in these
      exposed persons than in the average German population. To evaluate possible TCDD
      induced changes in the percentage of different lymphocyte subsets, we determined
      a large panel of lymphocyte subsets in the blood by flow cytometric analysis.
      Immunocompetence of T-and B-lymphocytes was tested by nitrogen
      (phytohemagglutinin, pokeweed mitogen)- induced lymphoproliferation assays and by
      assays using sensitive mixed-lymphocyte cultures. No significant differences
      could be detected between the individuals tested and controls for surface marker
      distribution or mitogen-induced lymphoproliferation TCDD-exposed subjects showed
      a reduced response to human lymphocyte antigen-allogeneic lymphocytes and
      interleukin-2-boosted proliferation. Responder cells of the dioxin-exposed
      persons proliferated less in response to irradiated stimulator cells (p < or =
      0.05), and the third-party mixed lymphocyte reaction against unirradiated
      stimulator cells revealed suppressive activity in the responder cell fraction
      compared to the controls (p < or = 0.01). Furthermore, the capacity of a pool of
      T cells isolated from TCDD-exposed subjects to proliferate upon interleukin-2
      stimulation was significantly diminished (p < or = 0.05). TCDD has a long-term
      immunosuppressive-effect on T-helper cell function, which is mediated more likely
      by a reduced functionality of individual cells rather than by a reduction in
      absolute cell numbers in the peripheral blood.

PMID- 8732954
TI  - Seasonal and spatial variation of the bacterial mutagenicity of fine organic
      aerosol in southern california.
AB  - The bacterial mutagenicity of a set of 1993 urban particulate air pollution
      samples is examined using the Salmonella typhimurium TM677 forward mutation
      assay. Amibent fine particulate samples were collected for 24 hr every sixth day
      throughout 1993 at four urban sites, including Long Beach, central Los Angeles,
      Azusa, and Rubidoux, California, and at an upwind background site on San Nicolas
      Island. Long Beach and central Los Angeles are congested urban areas where air
      quality is dominated by fresh emissions from air pollution sources; Azuasa and
      Rubidoux are located farther downwind and receive transported air pollutants plus
      increased quantities of the products of atmospheric chemical reactions. Fine
      aerosol samples from Long Beach and Los Angeles show a pronounced seasonal
      variation in bacterial mutagenicity per cubic meter of- ambient air, with maximum
      in the winter and a minimum in the summer. The down-wind smog receptor site at
      Rubidoux shows peak mutagenicity (with postmitochondrial supernatant but no peak
      without postmitochondrial supernatant) during the September-October periods when
      direct transport from upwind sources can be expected. At most sites the
      mutagenicity per microgram of organic carbon from the aerosol is not obviously
      higher during the summer photochemical smog period than during the colder months.
      Significant spatial variation in bacterial mutagenicity is observed: mutagenicity
      per cubic meter of ambient air, on average, is more than an order of magnitude
      lower at San Nicolas Island than within the urban area. The highest mutagenicity
      values per microgram of organics supplied to the assay are found at the most
      congested urban sites at central Los Angeles and Long Beach. The highest annual
      average values of mutagenicity per cubic meter of air sampled occur at central
      Los Angeles. These findings stress the importance of proximity to sources of
      direct emissions of bacterial mutagens and imply that if important mutagen
      forming atmospheric reactions occur, they likely occur in the winter and spring
      seasons as well as the photochemically more active summer and early fall periods.

PMID- 8732955
TI  - Changes in sleeping and basal energy expenditure and substrate oxidation induced
      by short term thyroxin administration in man.
AB  - The present study was designed to explore the thermogenic effect of thyroid
      hormone administration and the resulting changes in nitrogen homeostasis. Normal
      male volunteers (n = 7) received thyroxin during 6 weeks. The first 3-week period
      served to suppress endogenous thyroid secretion (180 micrograms T4/day). This
      dose was doubled for the next 3 weeks. Sleeping energy expenditure (respiratory
      chamber) and BMR (hood) were measured by indirect calorimetry, under standardized
      conditions. Sleeping heart rate was continuously recorded and urine was collected
      during this 12-hour period to assess nitrogen excretion. The changes in energy
      expenditure, heart rate and nitrogen balance were then related to the excess
      thyroxin administered. After 3 weeks of treatment, serum TSH level fell to 0.15
      mU/L, indicating an almost complete inhibition of the pituitary-thyroid axis.
      During this phase of treatment there was an increase in sleeping EE and sleeping
      heart rate, which increased further by doubling the T4 dose (delta EE: +8.5 +/-
      2.3%, delta heart rate +16.1 +/- 2.2%). The T4 dose, which is currently used as a
      substitutive dose, lead to a borderline hyperthyroid state, with an increase in
      EE and heart rate. Exogenous T4 administration provoked a significant increase in
      urinary nitrogen excretion averaging 40%. It is concluded that T4 provokes an
      important stimulation of EE, which is mostly mediated by an excess protein
      oxidation.

PMID- 8732956
TI  - Body mass index and cardiovascular disease risk factors in seven Asian and five
      Latin American centers: data from the International Clinical Epidemiology Network
      (INCLEN).
AB  - We have tested the hypothesis that the relationship between body mass index (BMI)
      and other cardiovascular disease (CVD) risk factors as well as socioeconomic
      status is different in five Latin American populations (where BMI is high) and
      seven Asian populations (where BMI is low). Random samples of approximately 200
      males aged between 35 and 65 years were selected from 12 general or industrial
      populations in Latin America and Asia. Standardized measures of height, weight,
      blood pressure, blood cholesterol, cigarette smoking, highest level of completed
      education, occupation and income were made. The mean BMI (kg/m2) was 25.3 (SD
      3.74) in the five Latin American populations (which were all urban), 22.2 (SD
      3.24) in the four Asian urban populations and 21.4 (SD 3.33) in the three Asian
      rural populations. Despite the differences in mean BMI levels, statistically
      significant positive relationships of a similar magnitude were seen between BMI
      and blood pressure levels in Latin America and Asia. Similarly, there was a
      statistically significant positive relationship found between BMI and total
      cholesterol in both Latin American and Asian urban samples, but of a higher
      magnitude in Asian rural samples. Current cigarette smokers had significantly
      lower BMI than ex-smokers or never smokers in Latin America and Asia. In Asia,
      there were statistically significant positive associations between BMI and levels
      of education and income as well as with occupation-these relationships were
      stronger for education and occupation in rural than in urban samples. There were
      no statistically significant associations between BMI and these measures of
      socioeconomic status in Latin America. The similarities of the associations
      between BMI and blood pressure and cholesterol levels in the two groups suggest
      that efforts to reduce BMI in all populations is likely to be important in
      reducing risk of CVD. Preventing the future rise of BMI in populations where BMI
      is still relatively low is a high priority. The difference in association between
      BMI and socioeconomic status in the different population groups requires study of
      the way sociocultural factors influence behavior that determines BMI levels.

PMID- 8732957
TI  - Nutrition and physical activity program to attenuate obesity and promote physical
      and metabolic fitness in elementary school children.
AB  - Obesity and low levels of physical and metabolic fitness are risk factors for
      cardiovascular disease and diabetes. The purpose of this investigation was to
      attenuate obesity and improve physical and metabolic fitness in elementary school
      children. Schools have the opportunity, mechanisms, and personnel in place to
      deliver nutrition education, fitness activities, and a school food service that
      is nutritious and healthy. Cohorts from grades 3 to 5 in two school districts in
      rural Nebraska (Intervention/Control) participated in a 2-year study of physical
      activity and modified school lunch program. Data collection for aerobic capacity,
      body composition, blood chemistry, nutrition knowledge, energy intake, and
      physical activity was at the beginning and end of each year. Int received
      enhanced physical activity, grade specific nutrition education, and a lower fat
      and sodium school lunch program. Con continued with a regular school lunch and
      team sports activity program. At year 2, Int lunches had significantly less
      energy (9%), fat (25%), sodium (21%), and more fiber (17%). However, measures of
      24-hour energy intake for Int and Con showed significant differences for sodium
      only. Physical activity in the classroom was 6% greater for Int compared to Con
      (p < 0.05) but physical activity outside of school was approximately 16% less for
      Int compared to Con (p < 0.05). Body weight and body fat were not different
      between schools for normal weight or obese children. No differences were found
      for cholesterol, insulin, and glucose; however, HDL cholesterol was significantly
      greater and cholesterol/HDL was significantly less for Int compared to Con (p <
      0.05). It appears that compensation in both energy intake and physical activity
      outside of school may be responsible for the lack of differences between Int and
      Con.

PMID- 8732958
TI  - Mental distress, obesity and body fat distribution in middle-aged men.
AB  - Previous epidemiological studies have suggested that psychiatric symptoms are
      associated with obesity and abdominal distribution of body fat in women. The aim
      of the present study was to examine this in middle-aged men. In 1992 a cluster
      selected cohort of 1040 men born in 1944 (participation rate 79.9%) was examined.
      Registrations of symptoms of depression and anxiety, sleep disturbances,
      psychosomatic disease as well as degree of life satisfaction were analyzed in
      relation to body mass index (BMI) and the waist/hip circumference ratio (WHR). In
      univariate analyses both BMI and WHR correlated with these factors. BMI and WHR
      were, however, closely interrelated (p = 0.61), necessitating analyses of
      separate, independent relationships in multivariate analyses. When adjusted for
      WHR all the significant relationships with BMI disappeared. In contrast the WHR,
      adjusted for BMI, showed remaining significant associations with the use of
      anxiolytics (p = 0.018), hypnotics (p = 0.029), antidepressive drugs (p = 0.008),
      degree of melancholy (p = 0.002), and life satisfaction (p = 0.002, negative),
      difficulties to sleep (p = 0.014) and fall asleep (p = 0.047), tendency to wake
      up from sleep (borderline, p = 0.070) and dyspepsia (p < 0.001). Since smoking
      and alcohol are known to influence on the WHR, these factors were, in addition to
      BMI, entered into the analyses as confounding variables. The mentioned
      associations then remained statistical significant (use of hypnotics borderline,
      p = 0.074) except difficulties to fall asleep and tendency to wake up. It was
      concluded that in contrast to BMI, the WHR is associated with symptoms of
      depression and anxiety with associated sleep disturbances, as well as
      psychosomatic symptoms and dissatisfaction. It was hypothesized that the
      mechanism involved might be increased secretion of cortisol, directing storage
      fat to central adipose tissue depots.

PMID- 8732959
TI  - Familial clustering of abdominal visceral fat and total fat mass: the Quebec
      Family Study.
AB  - The evidence for common familial factors underlying total fat mass (estimated
      from underwater weighing) and abdominal visceral fat (assessed from CT scan) was
      examined in families participating in phase 2 of the Quebec Family Study (QFS)
      using a bivariate familial correlation model. Previous QFS investigations suggest
      that both genetic (major and polygenic) and familial environmental factors
      influence each phenotype, accounting for between 55% to 71% of the phenotypic
      variance in fat mass, and between 55% to 72% for abdominal visceral fat. The
      current study suggests that the bivariate familial effect ranges from 29% to 50%.
      This pattern suggests that there may be common familial determinants for
      abdominal visceral fat and total fat mass, as well as additional familial factors
      which are specific to each. The relatively high spouse cross-trait correlations
      usually suggest that a large percent of the bivariate familial effect may be
      environmental in origin. However, if mating is not random, then the spouse
      resemblance may reflect either genetic or environmental causes, depending on the
      source [i.e., through similar genes or cohabitation (environmental) effects].
      Finally, there are significant sex differences in the magnitude of the familial
      cross-trait correlations involving parents, but not offspring, suggesting complex
      generation (i.e., age) and sex effects. For example, genes may turn on or off as
      a function of age and sex, and/or there may be an accumulation over time of
      effects due to the environment which may vary by sex. Whether the common familial
      factors are genetic (major and/or polygenic), environmental, or some combination
      of both, and whether the familial expression depends on sex and/or age warrants
      further investigation using more complex models.

PMID- 8732960
TI  - A double-blind randomized placebo-controlled trial of sibutramine.
AB  - Sibutramine is a beta-phenethylamine which blocks reuptake of norepinephrine and
      serotonin. In this clinical study, a group of 173 patients were randomized to
      treatment with sibutramine at doses of 1, 5, 10, 15, 20 or 30 mg/d and were
      compared with placebo in a 24-week double-blind trial. There was a dose-dependent
      reduction in body weight, with doses of 10, 15, 20 and 30 mg being significantly
      greater than placebo. Weight loss was still continuing in the highest three doses
      at the end of the study. When drugs were discontinued patients regained weight,
      as expected. Side effects were generally mild and were most evident in the group
      treated with the highest dose. These studies suggest that sibutramine may be a
      valuable new drug for treatment of obesity.

PMID- 8732961
TI  - Factors related to body weight changes during and after pregnancy: the Stockholm
      Pregnancy and Weight Development Study.
AB  - The Stockholm Pregnancy and Weight Development Study is a prospective study of
      body weight changes in women, whose maternity unit charts were reviewed and who
      were then invited for a 1-year follow-up, including weigh-in sessions and
      questionnaires on dietary habits, physical activity and socio-demographic
      factors. Total weight gain during pregnancy was related to weight gain already
      during the first trimester. Women reporting previous weight cycling had slightly
      higher weight gain during pregnancy. Successful return towards pre-pregnancy
      weight was found more often in women with regular breakfast and lunch habits.
      Lactation had only a small effect on weight loss after delivery, independent of
      eating habits. Lack of physical activity was more common in women who had low
      lactation scores. Twenty-eight percent reported an increased interest in sweets
      during pregnancy; these women increased 1 to 2 kg more than others in weight
      during pregnancy. Postpartum weight retention was more affected by lifestyle
      changes during and after pregnancy than by factors before pregnancy.

PMID- 8732962
TI  - Inhibition of cortisol secretion by dexamethasone in relation to body fat
      distribution: a dose-response study.
AB  - There is now evidence of a hypersensitive hypothalamo-pituitary-adrenal (HPA)
      axis in subjects with an elevated waist/hip circumference ratio (WHR), an
      indicator of the centralization of body fat stores. The activity of the HPA axis
      is regulated by central glucocorticoid receptors, whose activity can be tested by
      the administration of exogenous glucocorticoids, which normally inhibit cortisol
      secretion. In this study, dexamethasone (dex) was administered in random order in
      doses of 0.05, 0.125, 0.25 and 0.5 mg at 10 p.m. with measurements of serum
      cortisol in the morning (8 a.m.) of this and the following day. The test was
      performed on 22 apparently healthy men, 40 to 60 years of age, recruited from
      laboratory personnel, outpatient clinics or advertisements in a newspaper. Eight
      had a body mass index (BMI) (kg/m2) of < 25 and 14 of > 25. Twelve men had a
      waist hip ratio (WHR) of < 1.0 and 10 men had a WHR of > 1.0. Cortisol values at
      baseline were correlated inversely with WHR and were usually lower in men with a
      high (> 1.0) rather than a low than low (< 1.0) WHR after dex inhibition. There
      was apparently no inhibition by dex at 0.05 and 0.125 mg on average in men with a
      WHR of > 1.0. In addition, the inhibition at 0.5 mg dex correlated negatively
      with the WHR and was significantly lower (p < 0.05) in men with a WHR of > 1.0
      than in men with a WHR of < 1.0. None of these differences or relationships was
      found to be dependent on BMI. It is concluded that men with an elevated WHR
      experience a decrease in the inhibition of cortisol secretion by dex. It is
      suggested that this could explain or contribute to the elevated sensitivity of
      their HPA axis. Furthermore, lower morning cortisol concentrations suggest a
      change in diurnal secretion patterns.

PMID- 8732963
TI  - Ontogeny of the response to thyroxine (T4) in the porcine fetus:
      interrelationships between serum T4, serum insulin-like growth factor-1 (IGF-1)
      and differentiation of skin and several adipose tissues.
AB  - The temporal aspect of thyroxine (T4) enhanced development of several fetal
      adipose tissue depots (locations) and skin was examined in the present study. On
      day 70 of gestation pig fetuses were either hypophysectomized (hypox), hypoxed
      and implanted with T4 pellets or left intact (control). Subsequently, fetuses
      were removed for study at either 73, 75, 80, 85 and 90 days of gestation. Serum
      levels of T4 and insulin-like growth factor I (IGF-I) were significantly elevated
      by T4 after 3 days of treatment and throughout the study. T4 treatment enhanced
      development of skin, inner and outer subcutaneous (SQ) adipose tissue and
      adipocyte lobules around hair follicles (HFL's) but degree of response and
      response time were tissue or depot dependent. The T4 response time was shortest
      for skin and HFL's, longest for inner SQ and intermediate for the outer SQ.
      Considering the entire treatment period, magnitude of the T4 response was much
      greater for skin and HFL's than for outer and inner SQ tissues. Possibly, these
      developmental characteristics indicate that T4 directly influences skin and HFL's
      and indirectly influences inner SQ adipose tissue by increasing production of a
      locally produced adipogenic growth factor. Furthermore, developmental
      characteristics (morphological) indicated that putative local growth factor
      mediation of T4 action may depend on stage of development or maturity of the
      tissue. IGF-I is clearly the most logical candidate as a putative local mediator
      of T4, but evidence at the molecular level is needed to prove this suggestion.
      Regardless, the particular adipose tissue location or depot is an important
      aspect of hormone responsiveness during the critical or sensitive period of fetal
      adipose tissue development.

PMID- 8732964
TI  - "Diet, exercise and behavior therapy": a cautionary tale.

PMID- 8732965
TI  - Obesity treatment and attrition: no relationship to obesity level.

PMID- 8732966
TI  - The accumulation of visceral adipose tissue may be influenced by intra-abdominal
      temperature.
AB  - Despite the established link between visceral obesity and major chronic diseases,
      little is known about physiologic factors that directly and specifically lead to
      the accumulation of visceral fat. I hypothesize that reduced intra-abdominal
      temperature might be a physical factor underlying the partitioning of adipose
      tissue to the intra-abdominal region rather than the periphery. The hypothesis is
      supported by biochemical reports that rat and bovine lipoprotein lipase have
      increased activity when incubated at lower temperatures. Persons exercising in
      cool water have been found to preserve subcutaneous fat whereas comparable
      exercise without local cooling results in subcutaneous fat loss. Pima Indians, a
      group that commonly acquires extreme levels of visceral fat, have been found to
      have lower intra-abdominal temperatures during sleep than weight-matched European
      Americans. In a study of four young men and four young women, I have noted that
      mean intra-abdominal basal temperatures were higher for women than men (36.51 +/-
      0.18 degrees C vs. 35.91 +/- 0.11 degrees C; p = .0014). Since the men are more
      likely to acquire visceral obesity at later age, this also provides support for
      my hypothesis. Investigators might wish to examine further the temperature
      dependence of adipose-tissue lipoprotein lipase, the temperature variation
      between sites of adipose tissue, and the effects of foods, physical activities,
      smoking and drugs on localized body temperature.

PMID- 8732967
TI  - Obesity and surgery for a chronic disease.

PMID- 8732968
TI  - Metabolic observations in patients with jejunocolic shunts. 1963.

PMID- 8732969
TI  - Gastric bypass in obesity. 1967.

PMID- 8732970
TI  - "Been there, done that".

PMID- 8732973
TI  - Female genital mutilation condemned.

PMID- 8732975
TI  - Republican candidates beware--student nurses polled on politics.

PMID- 8732978
TI  - Needs and resources. The lived experience of homeless men.
AB  - 1. Interviews were conducted with 150 homeless men, who were in a situational
      crisis, were severely and persistently mentally ill, or were alcohol/drug
      dependent, about their perceived needs and resources. 2. The most pressing needs
      for men in all groups were for permanent housing, a job, and income. 3. A variety
      of approaches or community resources were utilized to meet needs for food, sleep,
      elimination, clothing, hygiene/laundry, safety, privacy, and income.

PMID- 8732979
TI  - Counseling needs of women with breast cancer: what the women tell us.
AB  - Research has demonstrated that some women treated for breast cancer are at risk
      for significant and persistent emotional distress and disrupted quality of life.
      Factors identified that appear to make women psychologically vulnerable include
      younger age at diagnosis, a history of high life stress or depression prior to
      diagnosis, and more advanced disease. Research has quickly moved to develop and
      implement psychological interventions to help these women, although little is
      known about the patients' perceptions of their need for, and use of, such
      services. This article presents research that focuses on the perceptions of the
      women themselves using a survey technique.

PMID- 8732980
TI  - Violence in public sector psychiatric hospitals. Benchmarking nursing staff
      injury rates.
AB  - 1. Violence toward healthcare workers, particularly psychiatric nursing staff,
      has only recently been identified as a workplace health hazard. An occupational
      health perspective underscores the need for proactive monitoring and heightens
      incentives for prevention through the introduction of external regulation. 2.
      Nursing staff injury rates from violence alone are higher than injuries seen in
      industries traditionally considered high risk such as mining, lumber, and heavy
      construction. Nursing employment categories at particular risk include
      psychiatric technicians, male staff, and on-unit supervisory personnel. 3. It is
      exceedingly difficult to accurately measure the extent of violence in a given
      facility and injury rates are known to underestimate the actual number of violent
      events that occur. Nursing staff, labor organizations, and managers must work
      toward more reliable monitoring and risk prevention programs.

PMID- 8732981
TI  - Putting feeding back into the hands of patients.
AB  - At the Behavioral Health Unit of Baton Rouge General Medical Center, the author
      and registered dietitians of the Clinical Nutrition Department developed "utensil
      less" diets for patients with acute psychiatric conditions. Initially, the diet
      was developed for patients with dementia; however, the staff quickly realized
      that the diet would be appropriate for patients with many acute psychiatric
      disorders, or for those patients with physical limitations. The "Dementia Diet"
      includes five nutritionally balanced, small meals each day, consisting of finger
      foods such as sandwiches, vegetable sticks, fruit slices, and other items that
      patients can eat on their own without feeding assistance or utensils (Figure).
      After introducing the diet on the Behavioral Health Unit, the staff found that 7
      of 10 patients on the diet improved their food intake and gained weight. Not only
      were nutritional needs met, but mealtimes became more enjoyable for the patients,
      families, and staff (Table). Unit safety advanced, and most importantly, quality
      of life and self-esteem were cultivated by helping adult patients regain some of
      their independence associated with meal times.

PMID- 8732982
TI  - Sundown syndrome: etiology and management.
AB  - 1. Although no clear definition of "sundowning" or "sundown syndrome" exists in
      the literature, most health care professionals affix either of these terms to the
      behavior observed in patients with dementia associated with increased agitation
      and confusion that occurs in the late afternoon. 2. Specific etiologic hypotheses
      that relate to sundowning behavior include disturbance in Rapid Eye Movement
      (REM) sleep, episodes of sleep apnea, and a deterioration of the suprachiasmatic
      nucleus of the hypothalamus. 3. Management of sundowning behavior includes the
      identification and treatment of any physiologic factors, low doses of specific
      neuroleptics, and nonpharmacological interventions such as restriction of daytime
      sleep, exposure to bright lights during the day, and mild activity schedules.

PMID- 8732983
TI  - Role of the transversus perinei profundus muscle on voiding: the meaning of UPmax
      in patients with paralyzed urethral sphincter.
AB  - Urodynamic study of 66 patients with caudal injury and of 7 patients who
      underwent saddle block was evaluated by putting emphasis on the maximal pressure
      of the urethra (UPmax). The static pressure of 49.7 +/- 10.8 cm H2O in the
      membranous urethra of the patients with completely paralyzed sphincter raised the
      question that some active muscle that functions to open the membranous urethra
      must have been working during physiological urination. Urodynamic findings of
      detrusor sphincter relationship, monitored by pressure and electromyogram (EMG)
      measurement, suggested that the combined reflections of the pelvic floor muscle
      and urethral sphincter are present. We concluded that this would be induced by
      the transversus perinei profundus muscle contraction and the urodynamic
      interpretation would be re-integrated on the role of this muscle on active
      urethral opening mechanism.

PMID- 8732984
TI  - Stress urinary incontinence due to a low-pressure urethra: a socially
      invalidizing disease.
AB  - To compare the quality of life and clinical findings of patients with low
      pressure urethra (LPU: < or = 20 cm H2O) with those of stress urinary incontinent
      (SUI) patients without LPU, and to compare the quality of urethral sphincter (US)
      muscle innervation parameters in LPU patients with those in control continent
      patients. Historical, clinical, urodynamic, and US muscle innervation parameters
      were compared in 38 LPU (group 1), 241 SUI (group 2), and 7 control patients
      (group 3). In comparison with group 2, the incidence of previous surgery and
      daily incontinence episodes, SUI severity, and pad test values were significantly
      higher in group 1, whereas the incidence of previous traumatic deliveries was the
      same in both groups. The mobility of the bladder neck assessed by the Q-Tip test
      was significantly reduced in group 1. In comparison with group 3, US motor unit
      potential (MUP) duration and pudendal motor latencies to the urethral sphincter
      (PMLUS) were increased in LPU group 1 patients, whereas there was no difference
      in these parameters between LPU patients with or without previous incontinence
      surgery. Fifty-three percent of our LPU patients had normal PMLUS, but showed
      signs of abnormal reinnervation on quantitative electromyography. Three nullipara
      LPU patients had normal MUP durations and PMLUS values, but a decreased area in
      response to pudendal nerve stimulation. Apart from a rare form of LPU in
      nullipara patients, probably due to a dysgenesis of their US muscle, LPU patients
      suffer from neuro-muscular damage responsible for a severe urinary invalidity.
      Previous incontinence surgery, as well as previous vaginal deliveries, may be
      responsible for such US damage.

PMID- 8732985
TI  - Maximal external electrical stimulation for treatment of neurogenic or non
      neurogenic urgency and/or urge incontinence.
AB  - Maximal electrical stimulation by intravaginal or intra-anal electrodes was used
      for treatment of 75 patients with complaints of urgency and/or urge incontinence.
      The patient group consisted of 51 women and 24 men. A neurogenic background was
      present in 30 of the women who had a diagnosis of multiple sclerosis, in the
      other 45 patients the pathology was idiopathic in nature. After 3 weeks of
      maximal electrical stimulation treatment, composed of 15 sessions of 20 minutes
      duration, 59% of the patients had urodynamic and subjective improvement and an
      additional 40% only subjective improvement. One patient found no benefit after
      this treatment. The effect lasted for at least 2 years in 64% of the idiopathic
      group. In the multiple sclerosis group relapse occurred within about 2 months. Re
      treatment of the failures was successful again immediately; the multiple
      sclerosis patients do need daily home stimulation treatments.

PMID- 8732986
TI  - Autologous adrenal medullary transplant in Parkinson's disease: critical review
      of our results in 13 patients.
AB  - Autotransplantation of the adrenal medullary to the caudate nucleus has been
      proposed for severe Parkinson's disease (PD). We describe our experience in 13
      patients using a transperitoneal approach to the medullary and craniotomy for the
      implant: the neurosurgical equipe's decision to opt for craniotomy made quick
      removal of the medullary with minimal morbidity more difficult. The surgical
      technique are discussed. We evaluated also the impact of the procedure on urinary
      symptoms and sexual disturbances associated with PD. Results were disappointing.
      Four patients died post-operatively. The neurological pattern improved in three
      men and one woman. No significant improvement was observed in the urological and
      sexual dysfunctions.

PMID- 8732987
TI  - Conventional, continuous, and telemetric monitoring of urodynamic parameters in
      non-human primates: a comparative study.
AB  - A comparison between three different techniques for monitoring urodynamic
      parameters in non-human primates was conducted in six adult female rhesus
      monkeys. This study was divided into two phases. In phase I, the animals were
      studied by conventional and continuous methods. During the study, uroflow and
      micturition pattern were obtained while the animals housed in a specially
      designed metabolic cage. Pressure transducers and EMG electrodes were surgically
      implanted. Then the animals were trained for 6 weeks to sit in a specially
      designed chair. Upon completion of the training period, continuous monitoring of
      the urodynamic parameters could be carried out for periods up to 14 hours. In
      phase II, the animals were studied with the conventional and telemetric methods.
      The same type of pressure transducers and EMG electrodes were implanted but they
      terminated in a radio transmitter powered by a long-life battery and controlled
      by a radio-operated switch. Conventional studies under ketamine sedation
      significantly increased bladder capacity, as well as the pressure at capacity (P
      < 0.05). Continuous monitoring was feasible, physiological, and more sensitive
      than the conventional techniques. Telemetric studies are superior to continuous
      monitoring, since the animal is not tethered to wires and provide data over a
      longer period of time. It is concluded that telemetric monitoring provides
      significantly different parameters, which could help in diagnosis and management
      of different voiding dysfunctions. In normal non-human primates, lower bladder
      capacity, higher maximum voiding pressure, higher bladder compliance, and higher
      incidence of detrusor instability without urethral relaxation were found.
      Telemetric urodynamic data on different pathological processes are currently
      unavailable and further work is needed in this area.

PMID- 8732988
TI  - Effects of estrogen and progestin replacement on the urogenital tract of the
      ovariectomized cynomolgus monkey.
AB  - Menopause is presumed to have a causative role in the development of female
      urinary incontinence. While some clinical trials have shown that estrogen can
      affect urinary tract function, our knowledge of the pathophysiologic changes
      resulting from menopause and hormone replacement therapy is poor. The cynomolgus
      monkey is a well-established model for study of menopause and hormone replacement
      therapy, particularly in the cardiovascular arena. We have utilized this animal
      model to determine the histologic effects of estrogen and estrogen/progestin
      replacement therapy in the proximal urethra and vagina. Estrogen and
      estrogen/progestin replacement induced an increase in the amount of vaginal but
      not urethral epithelium. Hormone replacement also resulted in a significant
      increase in the loose, vascular component of the connective tissue layer of the
      urethra. The cynomolgus macaque shows promise as a useful model for further study
      of the effects of hormone replacement on the lower urinary tract.

PMID- 8732989
TI  - Laplace's law and the risks and prevention of bladder rupture after
      enterocystoplasty and bladder autoaugmentation.
AB  - The purpose of this study was to utilize a rat model of bladder augmentation to
      determine the effect on bladder rupture pressure and volume of bladders augmented
      using myomyotomy autoaugmentation, intestinal patch ileocystoplasty alone, and a
      combination of ileocystoplasty and detrusor-myoplasty techniques. Four groups of
      female rats were studied: 1) sham animals served as controls, 2) ileocystoplasty,
      3) autoaugmentation using a myomyotomy technique, and 4) ileocystoplasty
      reinforced with a rectus muscle flap to envelop the augmented bladder
      (detrusormyoplasty). One month after surgery bladder rupture pressure and volume
      were determined by cystometry. Sham control rats manifested bladder rupture at a
      mean pressure of 154 +/- 43 mmHg and mean volume of 2.5 +/- 2.0 ml. Myomyotomy
      animals demonstrated a diminished mean rupture pressure and rupture volume (101
      +/- 13 mmHg and 1.2 +/- 0.4 ml, respectively) compared to control (both P <
      0.05). Ileocystoplasty animals demonstrated bladder rupture at a significantly
      higher volume of 4.0 +/- 1.9 ml than either myomyotomy or control animals (P <
      0.05), although rupture pressure of 111 +/- 49 mmHg did not differ significantly
      from control values (P = 0.55). The combination of ileocystoplasty and detrusor
      myoplasty yielded a statistically significant increase in rupture pressure (262
      +/- 108 mmHg) than the other three groups (P < 0.05). Rupture volume in this
      group of animals did not differ significantly from animals with ileocystoplasty
      but without detrusormyoplasty (P = 0.46). Bladder autoaugmentation results in a
      significantly reduced rupture pressure and volume than noted in the native
      bladder. Although ileocystoplasty significantly increases bladder capacity, the
      risk of urinary extravasation is also increased with this technique. The
      combination of ileocystoplasty and detrusor-myoplasty affords not only an
      increase in bladder capacity, but also significantly increases rupture pressure
      and thereby decreases the risk of bladder rupture after bladder augmentation.

PMID- 8732990
TI  - Morphometric data of canine sacral nerve roots with reference to electrical
      sacral root stimulation.
AB  - Experiments to investigate restoration of lower urinary tract control by
      electrical stimulation of the sacral nerve roots are mostly performed on dogs,
      yet little morphometric data (such as canine root and fiber diameter
      distributions) are available. The aim of this study was to acquire morphometric
      data of the intradural canine sacral dorsal and ventral roots (S1-S3). Cross
      sections of sacral roots of two beagle dogs were analyzed using a light
      microscope and image processing software. The cross-sectional area of each root
      was measured. The diameters of the fibers and the axons in the cross-sections of
      the S2 and S3 roots were measured and used to construct nerve fiber diameter
      frequency distribution histograms. The results show a unimodal diameter
      distribution for the dorsal roots and a bimodal distribution for the ventral
      roots. In addition the average ratio g of the axon diameter to fiber diameter was
      calculated for each root.

PMID- 8732991
TI  - Vitamin D receptor gene polymorphisms and osteoporosis.

PMID- 8732992
TI  - Clinical aspects of glucocorticoid sensitivity.
AB  - Recent studies demonstrate that primary (hereditary) abnormalities in the
      glucocorticoid receptor gene make 6.6% of the normal population relatively
      "hypersensitive" to glucocorticoids, while 2.3% are relatively "resistant." These
      abnormalities might explain why some individuals develop severe adverse effects
      during low dose glucocorticoid therapy, while others do not develop side effects
      even during long-term therapy with a much higher dose. Awareness of this
      heterogeneity in glucocorticoid sensitivity in the normal population might
      eventually allow the prediction of a "safe" dose of glucocorticoid in individual
      patients. "Resistance" to the beneficial clinical effects of glucocorticoid
      therapy in part of the patients with severe rheumatoid arthritis and asthma is
      probably rarely related to generalized primary (hereditary) glucocorticoid
      resistance. In the majority of patients this "resistance" seems to be acquired
      and localized to the sites of inflammation, where it reflects high local cytokine
      production, which interferes with glucocorticoid action. Recognition of
      localized, acquired glucocorticoid resistance is of great importance indicating
      as alternative drug therapy with other immune-modulating drugs like cyclosporin
      and methotrexate. Chronic high dose glucocorticoid treatment in such patients is
      ineffective in alleviating symptomatology, while generalized side effects occur,
      reflecting the patient's normal systemic sensitivity to these drugs.

PMID- 8732993
TI  - The roles of steroidogenic factor-1 in reproductive function.
AB  - The cytochrome P450 steroid hydroxylases are expressed in a tissue-specific and
      developmentally regulated manner, and the orphan nuclear receptor steroidogenic
      factor 1 (SF-1) participates in both aspects of regulated expression. SF-1 is
      expressed in mouse embryos from the inception of adrenal and gonadal development,
      suggesting that SF-1 plays important roles in their differentiation. SF-1 is also
      expressed in the embryonic pituitary gland and ventral diencephalon, suggesting
      additional roles within the hypothalamic-pituitary-steroidogenic organ axis. To
      examine the roles of SF-1 in vivo, we used targeted gene disruption to "knock
      out" the mouse gene encoding SF-1. Analyses of these knockout mice established
      roles of SF-1 at levels of endocrine development that include adrenal and gonadal
      differentiation, pituitary gonadotrope function, and formation of the
      ventromedial hypothalamic nucleus. These results indicate that SF-1 plays
      multiple roles in endocrine development that are essential for reproduction.

PMID- 8732994
TI  - Effects of estrogens and progestogens on the renin-aldosterone system and blood
      pressure.
AB  - Endogenous 17 beta-estradiol (E2) and low parenteral doses of exogenous E2 are
      vasodilators. High dose estrogens, especially ethinylestradiol (EE) and
      mestranol, stimulate the synthesis of hepatic proteins including coagulation
      factors, sex hormone binding globulin, and angiotensinogen (Aogen). In the steady
      state, high plasma levels of Aogen produce only a very small increase of
      angiotensin II (AII) and plasma renin activity, because AII inhibits the
      secretion of renin and lowers plasma renin concentration. However, the increase
      in AII is sufficient for a slight reduction in renal blood flow and a slight
      increase in exchangeable sodium and blood pressure; in susceptible women, blood
      pressure may rise considerably. Effects of estrogens on the brain may also be
      involved in blood pressure changes. Endogenous progesterone is a
      mineralocorticoid receptor antagonist. Endogenous or exogenous progesterone leads
      to sodium loss and a compensatory increase in renin secretion, plasma renin
      activity, AII, and plasma aldosterone, e.g. in the second half of the menstrual
      cycle. Synthetic progestogens are commonly devoid of the mineralocorticoid
      receptor antagonistic effect of progesterone, and some are weak estrogen receptor
      agonists. Combined use of EE and synthetic progestogens may therefore enhance
      estrogen effects on body sodium and blood pressure. A new progestogen
      (Drospirenone) with an antimineralocorticoid effect like that of progesterone is
      described that slightly lowers body weight and blood pressure in a contraceptive
      formulation together with EE. An almost ideal oral contraceptive would be
      progestogen like Drospirenone together with a low dose natural estrogen that does
      not stimulate Aogen synthesis. Since most oral formulations for postmenopausal
      estrogen replacement also stimulate hepatic protein synthesis (including Aogen)
      to some extent, the transdermal route of E2 application for contraceptive
      purposes should also be investigated, since it has reduced potential for
      undesirable side effects.

PMID- 8732995
TI  - Molecular basis of androgen insensitivity.
AB  - Male sexual differentiation and development proceed under direct control of
      androgens. Androgen action is mediated by the intracellular androgen receptor,
      which belongs to the superfamily of ligand-dependent transcription factors. In
      the X-linked androgen insensitivity syndrome, defects in the androgen receptor
      gene have prevented the normal development of both internal and external male
      structures in 46, XY individuals. The complete form of androgen insensitivity
      syndrome is characterized by 46, XY karyotype, external female phenotype, intra
      abdominal testes, absence of uterus and ovaries, blindly ending vagina, and
      gynecomastia. There is also a group of disorders of androgen action that result
      from partial impairment of androgen receptor function. Clinical indications can
      be abnormal sexual development of individuals with a predominant male phenotype
      with severe hypospadias and micropenis or of individuals with a predominantly
      female phenotype with cliteromegaly, ambiguous genitalia, and gynecomastia.
      Complete or gross deletions of the androgen receptor gene have not been
      frequently found in persons with the complete androgen insensitivity syndrome,
      whereas point mutations at several different sites in exons 2-8 encoding the DNA-
      and androgen-binding domain have been reported in both partial and complete forms
      of androgen insensitivity, with a relatively high number of mutations in two
      clusters in exons 5 and 7. The number of mutations in exon 1 is extremely low,
      and no mutations have been reported in the hinge region, located between the DNA
      binding domain and the ligand-binding domain. The X-linked condition of spinal
      and bulbar muscle atrophy (Kennedy's disease) is characterized by a progressive
      motor neuron degeneration associated with signs of androgen insensitivity and
      infertility. The molecular cause of spinal and bulbar muscle atrophy is an
      expanded length (> 40 residues) of one of the polyglutamine stretches in the N
      terminal domain of the androgen receptor.

PMID- 8732996
TI  - Regulation of primary response and specific genes in adrenal cells by peptide
      hormones and growth factors.
AB  - Using cultured bovine adrenal fasciculata cells (BAC), we investigated the
      effects of two hormones, corticotropin (ACTH) and angiotensin II (Ang-II) and two
      growth factors, insulin-like growth factors I (IGF-I) and transforming growth
      factor beta 1 (TGF beta 1), on the mRNA levels of nuclear proto-oncogenes of the
      Fos and Jun families and on the mRNA levels of genes expressed in BAC coding for
      ACTH and AT1 receptors, cytochrome P450scc and P450 17 alpha and 3 beta
      hydroxysteroid dehydrogenase (3 beta-HSD). ACTH and IGF-1 increased c-fos and jun
      B mRNA levels early with later increases in the levels of mRNA for the ACTH
      receptor and the three steroidogenic enzymes, and enhanced steroidogenic
      responses to both ACTH and Ang-II. In contrast, Ang-II increased mRNA coding for
      the three proto-oncogenes (cfos, c-jun, and jun-B), decreased those for P450 17
      alpha and 3 beta-HSD, and caused marked homologous and heterologous steroidogenic
      desensitization. TGF beta 1 increased only jun-B mRNA and markedly reduced BAC
      differentiated functions and steroidogenic responsiveness to both ACTH and Ang
      II. The long-term effects of ACTH on human adrenal fasciculata cells were
      comparable with those observed in BAC, whereas the long term effects of Ang-II
      and TGF beta 1 were different from those observed in BAC. Whether these species
      specific differences are related to a different effect of these factors on proto
      oncogene expression is not yet known.

PMID- 8732997
TI  - Mineralocorticoids, salt and high blood pressure.
AB  - Essential hypertensive patients often respond to treatments mitigating
      mineralocorticoid action, even though circulating levels of these steroids are
      within normal ranges. In addition to the kidney, mineralocorticoid or Type I
      receptors are found in the brain and vascular smooth muscle where they mediate
      effects associated with several forms of experimental hypertension. Studies in
      which discrete anatomic or functional areas of the brain have been ablated
      demonstrate that the periventricular areas of the hypothalamus and the central
      sympathetic and baroreceptor systems are crucial for the development of
      hypertension in the renoprival, DOCA salt, and Dahl salt-sensitive rat.
      Intracerebroventricular (i.c.v.) infusion of aldosterone in both rats and dogs at
      doses that do not raise serum levels above normal produce hypertension. The
      hypertension produced by systemic mineralocorticoid excess, adrenal regeneration,
      and i.c.v. or oral administration of glycyrrhetinic acid or carbenoxolone in
      genetically normotensive rats and by dietary salt in the Dahl salt-sensitive rat
      is inhibited by the i.c.v. infusion of a mineralocorticoid receptor antagonist or
      a Na+ channel-selective amiloride analog. Recent data demonstrate the
      extraadrenal synthesis of steroids in aortic endothelial cells, smooth muscle
      cells and the brain. The role of the extraadrenal synthesis of steroids raises
      new avenues for research into the causes of hypertension.

PMID- 8732998
TI  - Mineralocorticoid resistance.
AB  - Pseudohypoaldosteronism was first described in 1958 by Cheek and Perry, who
      reported an infant with severe salt wasting in the absence of any renal or
      adrenal defect. Since then several reports have described patients affected by
      symptoms consistent with resistance to mineralocorticoid action. The clinical
      picture is characterized by salt wasting and failure to thrive and is resistant
      to the administration of exogenous mineralocorticoids. Biological features are
      invariably high plasma and urinary aldosterone levels and elevated plasma renin
      activity associated with hyponatremia, hyperkalemia, and metabolic acidosis. The
      discovery of abnormal binding of aldosterone to the mineralocorticoid receptor
      (MR) in lymphocytes from affected patients, by analogy to findings in other
      syndromes of steroid hormone resistance, led to the hypothesis that the disease
      reflected a molecular defect in MR, which has prompted a series of molecular
      studies to characterize the defect. In this paper we review mechanisms of
      mineralocorticoid action, discuss the clinical features of mineralocorticoid
      resistance, overview the molecular characterization of the MR, and close with
      some pathophysiological hypotheses and questions.

PMID- 8732999
TI  - Apparent mineralocorticoid excess: type I and type II.
AB  - The syndrome of apparent mineralocorticoid excess (AME) is a heritable form of
      hypertension due to an inborn error of cortisol metabolism and is characterized
      by hypokalemia and low renin levels despite subnormal or normal levels of
      aldosterone and other known mineralocorticoids. The syndrome is attributable to
      congenital deficiency of the enzyme 11 beta-hydroxydehydrogenase (11 beta-HSD),
      which converts cortisol (F) to biologically inactive cortisone. This results in a
      prolonged half-life of F, which acts at the kidney level as a potent
      mineralocorticoid (MC). In fact, both F and aldosterone have similar affinities
      in vitro for type I MC receptor (MR), and 11 beta-HSD activity protects the MR in
      vivo from the higher circulating levels of F. The biochemical marker of this
      disorder is an increased ratio of tetrahydrocortisol (THF) + allo
      THF/tetrahydrocortisone (THE) in the urine, which has been found in more than 20
      patients described to date, together with evidence of a more general defect in
      steroid ring A reduction. Only a few cases (the so-called type II form) described
      in Italy differ from the classic form having a normal THF/THE ratio, but in both
      forms the ratio of free urinary F/E has recently been found to be similarly high.
      Dexamethasone is the treatment of choice but is often inadequate in long term
      control of high blood pressure. Acquired forms of AME are those consequent on
      abuse of licorice or carbenoxolone, which both inhibit 11 beta-HSD; the latter
      also inhibits the reverse 11-oxoreductase reaction leading to somewhat different
      abnormalities of urinary cortisol/cortisone. So far, two isoenzymes of 11 beta
      HSD have been purified and cloned; 11 beta-HSD type 1 is NADP-dependent, abundant
      in liver, lung, and testis, and catalyzes both 11 beta-dehydrogenation and 11
      beta-oxoreduction; no mutation in its gene was detected in patients with AME. A
      second NAD-dependent isoenzyme is present in kidney and placenta and catalyzes
      dehydrogenation only. Very recently (1995) two groups have independently
      demonstrated the presence of mutations in its gene, located in chromosome 16q22.
      New and co-workers found a point mutation in exon 6 of two affected siblings of
      an Iranian family, while White and co-workers in parallel studies showed point
      mutations or small deletions in both alleles in nine unrelated patients;
      importantly, expression studies showed minimal or absent activity for almost all
      the mutant sequences. No definite mutations have been so far identified in
      patients with AME type II. AME is thus the third single gene cause of human
      hypertension to be described, after glucocorticoid remediable aldosteronism in
      1992 and Liddle's syndrome in 1994.

PMID- 8733000
TI  - The 11 beta-hydroxysteroid dehydrogenase type II enzyme: biochemical consequences
      of the congenital R337C mutation.
AB  - The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) converts
      cortisol to cortisone, allowing the non-selective mineralocorticoid receptor to
      bind aldosterone. When the activity of this enzyme is compromised, as occurs in
      licorice intoxication or in the congenital syndrome of apparent mineralocorticoid
      excess (AME), there is marked sodium retention, hypokalemia, and hypertension.
      The first proof that this enzyme was defective in AME came from the
      identification of the R337C mutation in a number of siblings with the syndrome.
      Subsequent expression studies showed that the mutant had a Km one order of
      magnitude higher than the wild-type enzyme while in the cell-free system it was
      without detectable activity. In the present work we have extended our studies on
      this mutant and provide evidence that the mutant protein may also partially
      inhibit the wild-type enzyme in heterozygotes. Furthermore, experiments
      incorporating the protein synthesis inhibitor cycloheximide show that the mutant
      enzyme is less stable than the wild-type activity in intact cells. These results
      suggest that mutations in the 11 beta HSD2 enzyme may have multiple consequences
      for the mineralocorticoid target cell.

PMID- 8733001
TI  - Modulation of hypertensive heart disease by estrogen.
AB  - Left ventricular hypertrophy is an independent risk factor for morbidity and
      mortality in patients with hypertensive heart disease. Cardiac hypertrophy,
      associated with increased cardiac fibrosis and myocardial relaxation impairment,
      shows gender-based differences with significantly higher mortality in men. The
      role of estrogen in the pathogenesis of this process is poorly understood. After
      our previous demonstration that cardiac myocytes and fibroblasts contain
      functional estrogen receptors, we therefore investigated: 1) the influence of
      different estrogen metabolites on cardiac fibroblast growth; 2) the influence of
      different estrogen metabolites on the expression of the immediate early gene c
      Fos; 3) the influence of estrogen on the L-type calcium channel in
      cardiomyocytes. METHODS: 1) Neonatal rat cardiac fibroblasts were incubated with
      17 beta-estradiol, estrone, 2-hydroxyestrone, and 2-methoxyestradiol (all 10(-9)
      M). Bromodeoxyuridine incorporation was measured after 24 h. 2) c-Fos expression
      was demonstrated by immunoblotting. 3) L-type (Ca2+) current with and without 17
      beta-estradiol was assessed in adult guinea pig cardiomyocytes by whole cell
      patch clamp. RESULTS: Cardiac fibroblast growth was stimulated by estrogen
      metabolites with 2-hydroxyestrone as the most potent activator; in addition, 10(
      5) M 17 beta-estradiol reduced the L-type Ca2+ current by about 20% in
      cardiomyocytes. CONCLUSIONS: Estrogen induces both short term effects (non
      genomic) and long term effects (genomic) on the heart and may therefore account
      for gender- and age-based differences in hypertensive heart disease.

PMID- 8733002
TI  - A clinician looks at androgen resistance.
AB  - Androgen resistance in genetic males occurs when gonadotropins and testosterone
      are normal, but the physiological androgen response in androgen target organs is
      absent or decreased. In androgen-dependent target tissues two main defects may be
      found: 1) defective testosterone metabolism (5 alpha-reductase type 2 deficiency)
      and 2) anomalies in androgen receptors (androgen insensitivity syndrome (AIS)).
      The clinical manifestations of these defects vary from subjects with female
      external genitalia to subjects with mild forms of impaired masculinization. In
      particular, in the complete form of AIS (CAIS) the phenotype is feminine, and in
      the partial form (PAIS) the external genitalia are ambiguous with an extremely
      variable phenotype. The diagnosis requires clinical, hormonal, genetic, and
      molecular investigation for appropriate gender assignation and treatment. In AIS,
      cloning of androgen receptor cDNA using the polymerase chain reaction, denaturing
      gradient gel electrophoresis, and nucleotide sequencing have enabled a variety of
      molecular defects in the androgen receptor to be identified. The complexity of
      phenotypic presentation of AIS probably reflects the heterogeneity of androgen
      receptor gene mutations, but to date a relationship between genotype/phenotype
      has been difficult to establish, with the same point mutation reported to be
      associated with different phenotypic expressions. Other factors must therefore
      also contribute to the clinical presentation of AIS, although none have yet been
      identified. Establishing the functional consequences of androgen receptor
      mutations in vitro systems and correlating them with clinical presentation may
      ultimately provide an explanation for the variable clinical presentation of AIS
      and perhaps enable prediction of the response to androgen therapy in infants with
      PAIS.

PMID- 8733003
TI  - Estrogen receptors in the cardiovascular system.
AB  - Various direct effects of estradiol on arterial tissue suggest the presence of
      estrogen receptors (ER) in the vascular wall. The study of ER detection has made
      an important progress over the last 10 years with the advent and widespread use
      of monoclonal antibodies against the receptor protein. Using immunocytochemical
      methods and monoclonal antibodies, we have detected estrogen receptors in the
      tunica media of arteries from the reproductive tract; their concentration depends
      on the hormonal status. These receptors are apparently absent from saphenous
      veins (taken from patients undergoing surgical removal of varicose veins). We
      also document here results on the cardiovascular system we discuss their
      implications in blood vessel relaxation and cell proliferation.

PMID- 8733004
TI  - Molecular basis of glucocorticoid-resistant syndromes.
AB  - Generalized inherited glucocorticoid resistance (GIGR) is a rare syndrome
      characterized by elevated levels of plasma cortisol but lacking the symptoms of
      Cushing's syndrome. Biochemically, the condition is characterized by a relative
      resistance to glucocorticoids that can be compensated for by the elevated levels
      of cortisol. The inheritance pattern of GIGR is incompletely understood, and one
      of the central questions is whether there is a correlation between genotype and
      phenotype. Analysis of mutations within the receptor resulting in relative
      glucocorticoid resistance has identified two regions of clustered mutations in
      the proximity of previously identified affinity-labeled residues, the putative
      steroid-binding site. In the majority of cases, the mutation affects steroid
      binding and transactivation to the same degree, with the exceptions suggesting an
      explanation for the variability of the clinical manifestations. From a clinical
      point of view, in addition to preexisting genetic resistance to glucocorticoids,
      it is important to consider acquired changes in glucocorticoid receptor (GR) gene
      structure and organization, including alterations of noncoding sequences, and the
      importance of the resultant mutations, deletions, and other changes affecting
      receptor function. Finally, studies of New World primates and cell lines derived
      from hematologic malignancies constitute animal and human models for the
      molecular basis of glucocorticoid resistance where a number of inherited and
      acquired mutations in the GR gene have been demonstrated.

PMID- 8733005
TI  - Growth factors in steroid-responsive prostatic tumor cells.
AB  - Androgens stimulate the growth of prostatic carcinoma, possibly by modulating the
      activity of locally expressed growth factors. Recently, we have shown that an
      LHRH (or LHRH-like) system exerting an inhibitory action on cell proliferation is
      present in the human androgen-dependent prostatic tumor cell lines LNCaP. The
      following experiments have been performed in LNCaP cells to clarify whether LHRH
      might inhibit cell proliferation by interfering with the two major mitogenic
      factors for these cells: (a) testosterone (T), the major exogenous stimulating
      factor, and (b) epidermal growth factor (EGF), one of the locally produced growth
      factors. (a) It has been shown that an LHRH agonist (LHRH-A, Zoladex) counteracts
      the proliferative action of T in a dose-dependent way. To clarify whether LHRH
      might interfere with the activity of T in prostate tumors, LNCaP cells were
      treated with LHRH agonist over different time intervals, and the effects of
      treatment evaluated in terms of expression of androgen receptor mRNA. The data
      obtained indicate that LHRH-A does not affect androgen receptor expression at any
      time interval examined. (b) LHRH-A inhibits the mitogenic action of EGF on LNCaP
      cells and significantly reduces the concentration of EGF receptors in these
      cells. Experiments have been performed to explore whether LHRH-A might alter
      intracellular signaling mechanisms mediating the activity of EGF. In LNCaP cells
      LHRH-A blocks EGF-induced expression of the c-fos proto-oncogene but does not
      modify EGF-induced tyrosine phosphorylation of the EGF receptor. These data
      suggest that, in androgen-dependent prostate tumors, LHRH might inhibit cell
      proliferation by interfering with some but not all of the mechanisms mediating
      the mitogenic action of EGF. Possible interactions between LHRH and T-activated
      events still remain to be elucidated.

PMID- 8733006
TI  - Mitochondrial genes as sites of primary action of steroid hormones.
AB  - Steroid and thyroid hormones act on nuclear gene transcription by activating
      protein receptors, which in turn bind to hormone response elements (HREs). Among
      these cell-specific processes regulated by steroid receptors is energy metabolism
      through increased synthesis of respiratory enzymes. As some of these enzymes are
      encoded by both nuclear and mitochondrial genes, coordination of their synthesis
      is probable, inter alia at the transcriptional level. We have postulated a direct
      effect of steroid hormones on mitochondrial gene transcription and here present
      the following evidence in support of this hypothesis. 1) The human and rodent
      mitochondrial genomes contain nucleotide sequences similar both to type I and
      type II HREs. 2) Glucocorticoid receptors (GR) rapidly translocate from the
      cytoplasm into mitochondria after administration of glucocorticoids. This process
      has been reproduced in vitro and deletion of the N-terminal part of the
      glucocorticoid receptor stops translocation into mitochondria. 3) Gel shift
      analysis has demonstrated binding of GR to putative mitochondrial GR elements. 4)
      In transfection experiments, mitochondrial HREs confer dexamethasone inducibility
      on hybrid reporter constructs, abolished in the presence of excess RU38486. 5)
      Similar results were obtained for thyroid hormone receptor (TR alpha)
      localization, import, and binding to TR elements. These findings, taken with the
      demonstrated effects of steroid (and thyroid) hormones on mitochondrial
      transcription and respiratory enzyme biosynthesis, strongly support the
      hypothesis of a direct effect of steroid (and thyroid) hormones on mitochondrial
      gene transcription.

PMID- 8733007
TI  - Mineralocorticoids, salt, hypertension: effects on the heart.
AB  - In uninephrectomized rats on 1% NaCl solution to drink, aldosterone (0.75
      micrograms/h subcutaneously for 8 weeks) raises blood pressure and causes marked
      interstitial and perivascular cardiac fibrosis, effects not seen in animals on a
      low salt intake. In extending these initial findings, we have shown that cardiac
      fibrosis (i) is not reversed by correction of mineralocorticoid-induced
      hypokalemia; (ii) appears not to involve the plasma or tissue renin-angiotensin
      systems, as fibrosis is largely unaffected by concurrent administration of
      Losartan or Perindopril; (iii) is independent of cardiac hypertrophy, in that it
      is equally seen in right and left ventricles, and in rats rendered hypertensive
      without cardiac hypertrophy by the administration of 9 alpha-fluorocortisol; (iv)
      is independent of elevated blood pressure, in that it is found in normotensive
      animals infused peripherally with aldosterone and intracerebroventricularly with
      the mineralocorticoid receptor (MR) antagonist RU28318; (v) is via classical MR,
      in that it is blocked by concurrent administration of the MR antagonist potassium
      canrenoate; and (vi) may or may not be a direct cardiac effect, inasmuch as data
      for in vivo effects on collagen formation by cardiac fibroblasts are conflicting.
      Although there is a high probability that the action of aldosterone to cause
      cardiac fibrosis in this experimental model is an effect via non-epithelial MR,
      the locus of aldosterone action remains to be established, as do the molecular
      mechanisms linking MR occupancy by aldosterone and collagen deposition. In
      addition, and in particular, the mechanisms underlying the crucial contribution
      of high salt intake in this model of mineralocorticoid excess await exploration.

PMID- 8733008
TI  - Molecular genetic analysis of glucocorticoid and mineralocorticoid signaling in
      development and physiological processes.
AB  - To understand the role of glucocorticoid and mineralocorticoid signalling during
      development and in whole animal physiology, we have disrupted the mouse
      glucocorticoid and mineralocorticoid receptor gene by gene targeting. Most of the
      mice with a disrupted glucocorticoid receptor gene die within the first hours
      after birth due to severe lung atelectasis. Perinatal induction of gluconeogenic
      enzymes in the liver is impaired. Regulation of the glucocorticoid synthesis via
      the hypothalamic-pituitary-adrenal axis is perturbed, leading to increased plasma
      levels of corticosterone and adrenocorticotrophic hormone. Activation of the
      hypothalamic-pituitary-adrenal axis results in extensive hypertrophy and
      hyperplasia of the cortical zones of the adrenal and induction of genes involved
      in steroid biosynthesis. The adrenal medulla is disorganized and severely reduced
      in size; no cells capable of adrenaline synthesis can be detected.
      Mineralocorticoid receptor deficient mice die mainly at day 9/10 after birth.
      Weightloss precedes death of homozygous mutant mice and is correlated with an
      increase in the haematocrit. As a consequence of this mutation, plasma levels of
      renin and aldosterone are high elevated.

PMID- 8733009
TI  - Transcriptional regulation by steroid hormones.
AB  - Steroid hormones influence the transcription of a large number of genes by virtue
      of their interaction with intracellular receptors, which are modular proteins
      composed of a ligand binding domain, a DNA binding domain, and several
      transactivation functions distributed along the molecule. The DNA binding domain
      is organized around two zinc ions and allows the receptors to bind as homodimers
      to palindromic DNA sequences, the hormones responsive elements (HRE), is such a
      way that each homodimer contacts one half of the palindrome. Since the two halves
      are separated by three base pairs, the two homodimers contact the same face of
      the double helix. Before hormone binding, the receptors are part of a complex
      with multiple chaperones which maintain the receptor in its steroid binding
      conformation. Following hormone binding, the complex dissociates and the
      receptors bind to HREs in chromatin. Regulation of gene expression by hormones
      involves an interaction of the DNA-bound receptors with other sequence-specific
      transcription factors and with the general transcription factors, which is partly
      mediated by co-activators and co-repressors. The specific array of cis regulatory
      elements in a particular promoter/enhancer region, as well as the organization of
      the DNA sequences in nucleosomes, specifies the network of receptor interactions.
      Depending on the nature of these interactions, the final outcome can be induction
      or repression of transcription. The various levels at which these interactions
      are modulated are discussed using as an example the promoter of the Mouse Mammary
      Tumor Virus and its organization in chromatin.

PMID- 8733010
TI  - Cross-talk between cAMP and p53-generated signals in induction of differentiation
      and apoptosis in steroidogenic granulosa cells.
AB  - In each menstrual cycle only very few follicles in the mammalian ovary undergo
      maturation and ovulation while most of the follicles degenerate in the process of
      atresia. Moreover, in the absence of pregnancy, the newly formed corpora lutea
      will degenerate and disappear in the process of luteolysis. Recent studies
      suggest that ovarian follicular atresia is associated with DNA fragmentation and
      degeneration of follicular cells, characteristics of programmed cell death
      (apoptosis). Apoptosis can be induced in vitro, in primary granulosa cell
      culture, by serum deprivation and by induction of a high intracellular level of
      cAMP. This induction of apoptosis can be blocked by fibroblast growth factor,
      suggesting that receptor-medicated activation of a tyrosine kinase can serve as a
      survival signal. Apoptosis can also be induced in immortalized steroidogenic
      granulosa cells, transformed by SV40 DNA and Ha-ras oncogene, by overexpression
      of the wild-type p53 tumor suppressor gene in cAMP-stimulated cells. Omitting the
      cAMP stimulus prevents the p53-induced apoptosis in these cells, suggesting cross
      talk between p53 and c-AMP-generated signals in the induction of apoptosis.
      Steroidogenic activity in these cells, as well as in nontransformed granulosa
      cells, does not decline during apoptosis but is rather significantly elevated
      before total cell collapse occurs. Cytochemical studies using confocal laser
      microscopy, electron microscopy, and three-dimensional reconstruction reveal a
      specific reorganization pattern of proteasomes, the most abundant nonlysosomal
      protease, and of the steroidogenic organelles, such as mitochondria and lipid
      droplets, in the apoptotic cell. Our results suggest that compartmentalization of
      intracellular organelles during apoptosis permits proteolysis without interfering
      with steroidogenesis, characteristic of the differentiated phenotype of the
      granulosa cell. Moreover, cytoskeletal rearrangement may serve as a barrier
      between these cellular activities.

PMID- 8733011
TI  - Interaction of the Ubc9 human homologue with c-Jun and with the glucocorticoid
      receptor.
AB  - Glucocorticoid hormones convert the glucocorticoid receptor (GR) from an inactive
      cytosolic complex to a nuclear form that regulates transcription. Binding of GR
      to palindromic DNA-recognition sites (hormone response elements) leads to
      activated target gene transcription. GR also exerts negative actions on
      transcription, e.g., by interfering with the function of several other
      transcription factors such as AP-1, NK-kappa B, CREB, and Oct-1. Physical
      interactions of GR with AP-1 subunits are readily detectable but do not seem
      sufficient since nonrepressing GR mutants still interact in vitro, so that
      specific conformational changes and/or interactions with additional partner
      proteins may be required for negative action. In an attempt to find such partner
      proteins, we defined regions of c-Jun and GR essential for mutual interference
      and used in those a yeast two-hybrid screen for interacting proteins. Repeatedly
      we isolated overlapping cDNA sequences of one protein interaction with both c-Jun
      and GR. This protein does not interact with c-Fos or a non-repressing GR mutant
      and expressed in mammalian cells does not substantially affect AP-1 or GR
      activity. Interestingly, however, the protein rescues yeast cells from the toxic
      effects of the GR fragment used for screening. The protein represents the human
      homologue of the yeast E2 ubiquitin-conjugating enzyme, Ubc9; its specific
      interactions with both GR and c-Jun, but not mutant GR, suggest that it may exert
      physiologic regulatory functions.

PMID- 8733012
TI  - 11 beta-Hydroxysteroid dehydrogenases: key enzymes in determining tissue-specific
      glucocorticoid effects.
AB  - Recent studies have demonstrated that the interconversion of active and inactive
      glucocorticoids plays a key role in determining the specificity of the
      mineralocorticoid receptor and controlling local tissue glucocorticoid receptor
      activation. Two distinct isoforms of the enzyme 11 beta-hydroxysteroid
      dehydrogenase (11 beta-HSD) have been identified. 11 beta-HSD1 is NADPH-dependent
      and at its major site of action (the liver) is a reductase, converting cortisone
      to cortisol (11-dehydrocorticosterone to corticosterone in the rat). 11 beta-HSD2
      is NAD-dependent, is present in tissues such as the kidney and placenta, and
      converts cortisol to cortisone (corticosterone to 11-dehydrocorticosterone in the
      rat). Congenital or acquired deficiency of 11 beta-HSD2 produces the syndrome of
      apparent mineralocorticoid excess (SAME) in which cortisol gains access to the
      unprotected nonspecific mineralocorticoid receptor. The congenital deficiency is
      associated with mutations in the gene encoding the kidney isoform of 11 beta
      HSD2; the acquired form results from inhibition of the enzyme by licorice,
      carbenoxolone, ACTH-dependent steroids in the ectopic ACTH syndrome, and possibly
      circulating inhibitors of the enzyme. This paper focuses on recent evidence,
      which suggest that low levels of placental 11 beta-HSD2 result in increased
      exposure of the fetus to maternal glucocorticoid and low birth weight. In animal
      studies using the rat we have shown that birth weight is correlated positively
      and placental weight negatively with the level of placental 11 beta-HSD. Thus
      animals with low birth weight and large placentae were those likely to be exposed
      to the highest level of maternal glucocorticoid. In man a similar relationship
      was found with birth weight being significantly correlated either with placental
      11 beta-HSD activity or with the extent of cortisol inactivation by isolated
      perfused placental cotyledons. Administration of dexamethasone (which is poorly
      metabolized by placental 11 beta-HSD2) to pregnant rats resulted in decreased
      birth weight and the development of hypertension in the pups when adult. The same
      results were obtained when pregnant rats were given carbenoxolone, an inhibitor
      of placental 11 beta-HSD2. Low protein diet during pregnancy in the rat resulted
      in low birth weight of the pups, increased placental weight but decreased
      placental 11 beta-HSD activity, and adult hypertension. Thus increased
      glucocorticoid exposure of the fetus secondary to a failure of the normal
      inactivation of maternal glucocorticoid by the placental may be an important
      mechanism linking changes in the in utero environment and common adult diseases.

PMID- 8733013
TI  - Estrogen induction and contact phase activation of human factor XII.
AB  - This paper reviews data reported in the literature and results of our experiments
      on the transcriptional control of Factor XII by estrogens and on the activation
      of Factor XII in the plasma. Coagulation Factor XII (Hageman factor, FXII) is a
      serine protease secreted by the liver and activated by negative charged surfaces
      to play roles in fibrinolysis, coagulation, and inflammation. Multiple effects on
      hemostasis involving these processes via Hageman factor have been reported in
      relation to estrogen therapy. The nucleotide sequence of 3,174 base pair (bp) DNA
      at the 5' end of the Factor XII gene indicates that the Factor XII promoter is
      typical of TATA-less, liver-specific, and serine protease-type eukaryotic genes
      involved in clotting. In addition the Factor XII promoter contains at position 
      44/-31 a palindrome similar, but not identical, to an estrogen-responsive element
      (ERE) together with four hemisite EREs between positions -1314 and -608. These
      promoter regions may underlie the mechanism by which estrogens enhance Factor XII
      concentrations in plasma. In vivo, a 6-fold stimulation of FXII gene
      transcription by 17 beta-estradiol was observed in ovariectomized rats. In vitro
      a 230-bp promoter fragment of Factor XII (-181/+49) confers a strong 17 beta
      estradiol responsiveness onto a chlorampenicol acetyltransferase reporter when
      transiently co-transfected with the human estrogen receptor. The domain structure
      of Factor XII allows identification of those parts of the protein with particular
      functions. cDNA constructs, in which sequences coding for selected domains were
      deleted, were used to produce recombinant deleted Factor XII proteins in a
      vacinia virus expression system. To identify the domain(s) responsible for
      contact phase activation, these recombinant proteins were tested for their
      capacity to bind to negatively charged substrates, to become activated by
      kallikrein, and to sustain blood clotting and amidolytic activity. In addition to
      the N-terminal domain, the growth factor and kringle domains and, to a lesser
      extent, the polyproline region also interact with negatively charged surfaces and
      presumably thus contribute to activation.

PMID- 8733014
TI  - Cardiac arrest research in humans--insights into failure.
AB  - Cardiac arrest research in humans has failed to fulfil expectations generated by
      laboratory studies. This reflects a number of factors. It is difficult to perform
      clinical research in the setting of emergency cardiac resuscitation. Both the
      epidemiology and pathophysiology of sudden death present special problems to the
      clinical researcher. Laboratory studies and clinical trials have failed to
      faithfully mimic each other. Estimation of sample size and application of
      inclusion/exclusion criteria present special problems in methodology. Our focus
      on improving long term survival by changing one component of therapy may have
      been premature and obscured the utility of extant data. Many of these problems
      can be addressed through refinements in: laboratory models, our understanding of
      the underlying pathophysiology, estimation of sample size, the application of
      inclusion/exclusion criteria, the identification of the primary dependent
      variables and subgroups of interest, the overall quality of therapy. Clinical
      studies will not generate useful data until these issues, among others, have been
      addressed.

PMID- 8733015
TI  - The effect of experience of on-site physicians on survival from prehospital
      cardiac arrest.
AB  - Outcome from prehospital cardiac arrest was studied 1 year before (Period I) and
      after (Period II) a reorganisation of the work and the simultaneous change of all
      physicians participating in the care of prehospital patients in the emergency
      medical service system in Helsinki. There were 444 patients during Period I and
      395 patients during Period II. Resuscitation was initiated in 279 patients during
      Period I and in 323 patients (P < 0.001) during Period II. The number of patients
      with ventricular fibrillation who suffered a witnessed cardiac arrest due to
      presumed heart disease was 120 and 130, respectively. During Period I, 70 of
      these patients were successfully resuscitated and admitted to hospital, 41 (34%)
      survived to discharge home from hospital. Corresponding figures during Period II
      were 79 and 33 (25%, NS). Compared with Period I, a larger proportion of the
      successfully resuscitated patients either died in hospital or were discharged to
      an institution during Period II (P < 0.05).

PMID- 8733016
TI  - Educating residents: the effects of a mock code program.
AB  - Housestaff residents are often the primary participants in codes that occur in a
      hospital setting, yet it is unknown how much confidence and knowledge they
      possess in the management of these medical emergencies. A study to learn the
      effect of a mock code program on residents' level of confidence and knowledge
      regarding code situations was initiated in a children's tertiary care hospital.
      Thirty-three residents completed a questionnaire before initiation of the study.
      The questionnaire revealed that codes scare them (79%), and that they felt a need
      for more knowledge (76%) and more experience (82%) before supervising a code.
      They did not feel confident in performing certain procedures such as treating
      dysrhythmias (79%), obtaining i.v. access (64%), and doing intubations (30%).
      Sixteen residents then participated in mock codes, and the other seventeen
      residents served as controls. Compared to the pre-study questionnaire, residents
      who had participated in mock codes had more confidence in their ability to
      supervise and felt less of a need for more knowledge before supervising a code.
      The participants also felt more confident in obtaining i.v. access and performing
      intubations during a code situation. There was no difference in the pre- and post
      questionnaires of the control group. Residency programs are not meeting the
      educational and confidence needs of pediatric residents. A mock code program
      improves residents' perceived need for more knowledge before supervising a code
      and improves their confidence in doing many lifesaving procedures.

PMID- 8733017
TI  - The ventilation/compression ratio influences the effectiveness of two rescuer
      advanced cardiac life support on a manikin.
AB  - Time is of crucial importance during advanced cardiac life support (ACLS).
      Several parallel tasks have to be performed more or less simultaneously. The
      guidelines recommend a ventilation/ compression ratio of 1:5 in two-rescuer ACLS.
      This was compared with respect to time and CPR quality to an alternative method
      of a 2:15 ratio performed by one of the two rescuers freeing one rescuer to
      concentrate on other tasks than ventilation and chest compression. Seventeen
      paramedic students were trained in pairs in ACLS according to the European
      Resuscitation Council guidelines using an Ambu Mega Code trainer manikin. From a
      starting point of asystole paramedics were required to perform ECG analysis,
      intubation, i.v. access, adrenalin and atropine injection, flushing of the drug
      bolus before conversion to ventricular fibrillation followed by defibrillation in
      addition to ventilation and chest compression. Unpaired two-tailed Student t-test
      and the Fisher's exact test were used for statistical analysis, with a P-value
      less than 0.05 regarded as significant. It took significantly less time to
      perform successful CPR with the 2:15 ratio compared to the 1:5 ratio. The quality
      of the ventilations and compressions performed were not significantly different
      between 2:15 and 1:5 ratio. When two rescuers are performing ACLS, the 2:15 ratio
      method appears to be time saving vs. the 1:5. This could potentially improve the
      outcome after cardiac arrest.

PMID- 8733018
TI  - Heat exhaustion during mass pilgrimage--is there a diagnostic role for pulse
      oximetry?
AB  - Every year over 2 million pilgrims (Hajjis) gather from different countries to
      perform the sacred ritual, the fifth pillar of Islam, Hajj. Several nationalities
      from different climates come to Saudi Arabia which is located in a subtropical
      area with a hot and humid climate during the long summer season. This undertaking
      is characterised by several days of continuous physical, spiritual, and emotional
      exertion following their homeland. Several factors predispose them to heat
      exhaustion, such as the hot climate, excessive physical exercise, lack of
      acclimatisation, overcrowding, illiteracy, old age, diseases, and over zealous
      performance of Hajj during the peak sunshine hours. Several thousands of pilgrims
      suffer from heat exhaustion which is a minor form of heat illness that can easily
      be detected and treated. Patients are usually discharged having fully recovered,
      but if heat exhaustion is not treated immediately, it may result in heat stroke
      with serious sequelae. Cases that need further observation and management are
      admitted to hospital, particularly those who have associated medical disorders.
      This study was designed to investigate the role of pulse oximetry in detecting
      hypoxaemia in patients suffering from heat exhaustion. One hundred fifty-five
      patients from 26 different countries were enrolled in this study. Their ages
      ranged from 18 to 83 years. There were 51 (33%), 48 (31%), and 56 (36%) from
      Asia, the Middle East and Africa, respectively. One hundred thirty-four patients
      (86.5%) showed a form of hypoxia which necessitated O2 administration. Mild
      hypoxia (91-94% O2 saturation) was detected in 81 patients (52.3%) and moderate
      to severe hypoxia (< 90% O2 saturation) was detected in 53 (34.2%) patients.

PMID- 8733019
TI  - Excess mortality associated with the use of a rapid infusion system at a level 1
      trauma center.
AB  - The Rapid Infusion System (RIS) is a device which can deliver warm fluid and
      blood products rapidly and at precise rates. It has been in use since 1990 for
      the management of victims of major trauma at the R Adams Cowley Shock Trauma
      Center (STC) in Baltimore. Although the RIS is unquestionably a convenience to
      the anesthesiologist, no study to date has addressed its effect on patient
      outcome. We have therefore undertaken a retrospective review of all uses of the
      RIS on trauma patients during the years in which it has been available at the
      Shock Trauma Center, comparing actual patient mortality both to expected
      mortality derived from the STC Trauma Registry, and to matched historical
      controls who did not receive fluids via the RIS. A total of 527 patients were
      included in the study. The mean volume infused via the RIS was 9724 ml, and the
      total volumes ranged from 24-117 585 ml. Overall survival was significantly less
      than expected (52.9% vs. 61.8%, P < 0.001). Survival in penetrating trauma was
      similar to expected, but in blunt trauma it was considerably less (48.8% vs.
      63.0%, P < 0.001). Patients whose probability was between 0.1% and 0.9% also
      survived significantly less frequently than expected (44.3% vs. 57%, n = 105, P <
      0.008). In those patients who received less than 6000 ml via the RIS, the actual
      and expected survival rates were almost identical. In those receiving more than
      6000 ml (180 patients), the difference between actual and expected survival was
      striking (37.2% vs. 57.2%, P < 0.0001). As compared to matched control patients
      injured to the same extent during the same time period, patients who received
      fluids via the RIS had a 4.8 times greater chance of dying (95% confidence
      interval 2.4-7.1). These data call into question current protocols for rapid
      volume infusion in trauma management and point to the need for further
      prospective trials.

PMID- 8733020
TI  - Life after cardiac arrest; a retrospective study.
AB  - AIM: We decided to evaluate the life situation of the survivors after out-of
      hospital cardiopulmonary resuscitation (CPR). METHOD: CPR survivors who were 75
      years or younger at the time and who were discharged alive from the hospital were
      identified consecutively. Average follow-up time was 25.5 months, and at follow
      up 24% were deceased and 9% were lost. A questionnaire was completed by 93% and
      71% were positive to an interview. RESULTS: Cognitive functions were reduced as
      well as capacity to perform activities in daily living. This resulted in
      dependence on other persons for living (nursing homes) and a low return to work.
      Social isolation was a common complaint. The survivors also reported lower pain
      awareness than the reference population. As far as other aspects of health
      related quality of life, this small group show many similarities with previously
      evaluated post-infarction patients. CONCLUSION: Lower pain awareness should be
      taken into consideration when the CPR patients have ischemic heart disease. If
      possible, try to prevent social isolation.

PMID- 8733021
TI  - Increasing nitric oxide production improves survival in experimental hemorrhagic
      shock.
AB  - The purpose of this study was to evaluate the importance of nitric oxide (NO)
      upon outcome following hemorrhagic shock. L-Arginine, an NO precursor, and L
      NMMA, an inhibitor of NO synthesis, were added to resuscitation in a prospective,
      randomized, and double-blinded experimental model, and the effects upon blood
      pressure and survival were measured. METHODS: 60 Sprague-Dawley rats were
      anesthetized and subjected to phlebotomy to induce hemmorrhagic shock. After a 45
      min shock period, animals were resuscitated with either lactated Ringer's alone
      (control), L-NMMA in lactated Ringer's or L-arginine in lactated Ringer's. Blood
      pressure was monitored, and animals were observed for survival. As an additional
      control experiment, 15 additional animals underwent the same protocol, but
      underwent sham shock, i.e. were not haemorrhaged. RESULTS: L-NMMA increased blood
      pressure transiently following sham shock, but increased blood pressure to a
      greater extent and for a longer duration following hemorrhage. However, L-NMMA
      had no effect upon survival. L-Arginine had no measurable effect upon blood
      pressure, but significantly increased survival. CONCLUSION: NO may play an
      important role following hemorrhage. The effectiveness of L-NMMA as a pressor
      suggests that NO contributes to hypotension following hemorrhage. However,
      reversing hypotension with L-NMMA did not improve survival in this model. In
      contrast, L-arginine did not further lower blood pressure, but had significant
      survival benefit. This suggests a possible protective effect of NO after
      hemorrhage, perhaps by improving the distribution of capillary blood flow and/or
      by decreasing platelet aggregation and leukocyte adhesion within the
      microcirculation.

PMID- 8733022
TI  - The reversal of experimental hemorrhagic shock induced by nicotine and
      dimethylphenylpiperazinium is adrenal-dependent.
AB  - In a rat model of volume-controlled hemorrhagic shock causing the death of all
      control animals within 30 min, the intravenous injection of either nicotine (50
      micrograms/kg) or dimethylphenylpiperazinium (DMPP) (0.5 micrograms/kg) produced
      a rapid and sustained reversal of the shock condition, with 100% survival 2 h
      after treatment. Bilateral adrenalectomy completely prevented the anti-shock
      effect of the two drugs, even though administered at higher doses (150
      micrograms/kg in the case of nicotine; 10 micrograms/kg in the case of DMPP). It
      is concluded that stimulation of adrenaline release plays a fundamental role in
      the mechanism of action of nicotine- and DMPP-induced shock reversal.

PMID- 8733023
TI  - Structural basis of information capacity changes of sensory-motor cerebral cortex
      of rat brain during post-resuscitation period.
AB  - In a rat model of asphyxial cardiac arrest the volume of the sensory-motor cortex
      and the number of neurons and synapses were determined 90 min, 6 h, and 1, 3, 7,
      14, and 30 days post-resuscitation. The number of synapses was determined from
      serial fragmental sections, using selective contrast in ethanol solution of
      phosphorotungsten acid (PTA), and by cytoarchitectonic analysis on medium-thick
      sections. The sensory-motor cortex (SMC) volume did not change significantly
      during the subsequent 30 days after resuscitation. The number of neurons
      decreased from 2.462 +/- 0.082) x 10(6) pre-insult to (1.441 +/- 0.098) x 10(6)
      30 days after resuscitation. Damage was most severe in the small neuronal cell
      complexes of layers III-IV, which serve as an afferent cortical 'entrance'.
      Damage was least in the large neuronal cell complexes of layer V, which serves as
      an efferent cortical 'outlet'. The number of SMC synapses decreased from (5.920
      +/- 0.51) x 10(9) pre-insult to (3.441 +/- 0.305) x 10(9) 30 days after
      resuscitation. Damage was most severe in the synaptic pool of the cortical SMC
      'entrance'. An increase in the number of high-efficiency hypertrophic synaptic
      contacts was observed during the post-resuscitation period, which may
      significantly change interneuronal relationships.

PMID- 8733024
TI  - CT scanning as a helpful tool for decision-making during CPR.

PMID- 8733025
TI  - Risk of fires when using defibrillators in an oxygen enriched atmosphere.

PMID- 8733026
TI  - Towards early defibrillation--a nurse training programme in the use of automated
      external defibrillators.

PMID- 8733027
TI  - Antibodies in patients with inflammatory bowel disease and the apparent influence
      of medications.
AB  - Patients with inflammatory bowel disease (IBD) are known to have increased
      antibodies to several food and bacterial antigens. To assess selected isotype
      contributions in greater detail, we examined the concentrations of IgA, IgG, IgE,
      and IgG4 antibodies to five selected antigens, two of bacterial and three of food
      origin. Thirty patients with IBD and thirty matched healthy controls were
      studied. Most antibodies were increased in IBD patients compared to controls.
      Statistically significant increases were more frequent in Crohn's disease (CD)
      than in ulcerative colitis (UC). An unexpected finding was that IBD patients
      treated with sulfasalazine had statistically higher levels of most IgA antibodies
      than healthy controls, while steroid treated patients had lower levels. These
      findings suggest differing effects on the immune systems of IBD patients by each
      of these commonly used drugs.

PMID- 8733028
TI  - Non-specific autoantibodies in cardiomyopathies and myocardial infarction.
AB  - In the present study we evaluated the importance of autoimmune mechanisms in
      cardiomyopathies. Sera from 22 patients with dilated cardiomyopathy, 23 patients
      with hypertrophic cardiomyopathy, 24 patients with myocardial infarction and 40
      apparently healthy blood donors were tested with an immunoassay method for the
      presence of autoantibodies against dsDNA, ssDNA and cardiolipin. Elevated values
      of autoantibodies, mainly of the IgG subtype, were obtained in a high percentage
      of patients with cardiomyopathy (30-50%), as compared to the control group (5%).
      The incidence of these autoantibodies has been found significantly high in both
      groups of dilated and hypertrophic cardiomyopathies. Although further
      investigation is needed, it is concluded that the detection of these
      autoantibodies may contribute in the better understanding of the pathogenesis of
      cardiomyopathies and could be a useful tool for the diagnosis, follow up and
      prognosis of these patients.

PMID- 8733029
TI  - In vitro generation of soluble suppressor factor in murine chronic graft versus
      host (GVH) disease.
AB  - Veto cells are cells which suppress self directed cytotoxicity (CTX) regardless
      of the strain of origin of the cytotoxic effector cell. The mechanism by which
      veto cells inhibit self directed CTX is largely unknown. We have previously
      described the emergence of a veto cell in murine chronic graft versus host (CGVH)
      disease both in vivo and in vitro. Using an in vitro system in which veto cells
      are induced, we now report that a soluble factor is also induced which is capable
      of suppressing CTX. This cytotoxicity suppressing factor (CsF) is heat labile and
      has a molecular weight above 50 kD. The factor prevents the emergence of a
      cytotoxic effector cell. but is largely ineffective once the effector cell has
      functionally emerged. CsF is irreversible and is not restricted in its ability to
      inhibit anti-self CTX.

PMID- 8733030
TI  - Frederick Akbar Mahomed (1849-1884): pioneer of clinical research.
AB  - Professional historians generally treat the phrase 'what if' with pardonable
      scorn. It is a speculation which necessarily will never be tested in the real
      world. Nevertheless, there is a reasonable likelihood that, if typhoid fever had
      not carried off Frederick Akbar Mahomed at the age of 35, clinical research in
      Britain would have been both stronger and more highly developed at the beginning
      of the 20th century. Indeed, if he had lived to continue his most ambitious
      project, we would have had access to a unique source of clinical and
      epidemiological data 70 years before anything similar was contemplated.

PMID- 8733031
TI  - Review: the central role of calcium in the pathogenesis of cardiovascular
      disease.
AB  - Calcium-dependent processes play a central role in several different cells of the
      cardiovascular system including vascular smooth muscle and endothelial cells and
      also in monocytes, macrophages and platelets. In response to extracellular
      stimuli cytosolic calcium concentration increases. The increase is composed of
      two distinct phases. Firstly, calcium is released from intracellular stores via
      IP3. In the second phase calcium influx across the cell membrane is mostly
      responsible for the sustained rise in intracellular calcium concentration. This
      phase of the peak increase in cytosolic calcium is a prerequisite for sustained
      activation of the cell and the processes of vascular smooth muscle contraction
      and the activation of nuclear transcription factors for protein biosynthesis.
      Under ischemic conditions the regulatory systems which control the intracellular
      free calcium concentration consume a major portion of the cell's physiological
      energy supply (90%) and a decreased oxygen supply under ischemic conditions
      rapidly reduces the cell's capacity for intracellular calcium storage or outward
      transport across its membrane. Calcium antagonist drugs principally act on L-type
      calcium channels to reduce the influx of calcium into the the cells of the body.
      Since calcium antagonist drugs are able to influence a wide range of cellular
      processes which have been implicated in atherosclerosis, glomeruloscierosis, left
      ventricular hypertrophy and insulin resistance there are strong grounds for their
      use in a range of clinical disease states.

PMID- 8733032
TI  - Does high salt intake cause hyperfiltration in patients with essential
      hypertension?
AB  - In animal models of salt-dependent hypertension, hyperfiltration is associated
      with a faster decline in renal function and there is evidence that in
      hypertensive man, increased creatinine clearance is a marker of early
      hypertensive nephropathy. We have studied the influence of salt intake on the
      glomerular filtration rate (GFR) (Creatinine Clearance) in 14 patients with mild
      hypertension. Each patient was studied in random order and according to a
      crossover design, at habitual salt intake, at high salt intake (ie habitual
      +50/100 mmol/day) and at low salt intake (habitual -50/100 mmol/day). Protein,
      calcium and potassium intake was fixed across the three study periods. The
      control group was formed by seven healthy subjects. High salt intake, caused a
      significant (P < 0.01) increase in 24 h mean arterial pressure (MAP) and the
      expected suppression in plasma renin activity (PRA) and in plasma aldosterone.
      Seven patients were classified as salt-sensitive. The GFR was significantly
      higher (P < 0.01) at high salt intake (125 +/- 10 ml/min) than at habitual (113
      +/- 7 ml/min) and at low salt intake (97 +/- 6 ml/min). On aggregate urinary salt
      excretion was significantly related with the GFR (P < 0.01 by correlation
      analysis for repeated observations) and the slope of this relationship predicted
      that a 100 mmol/day increase in salt intake is associated with the 14.6 ml/min
      rise in the GFR. The relationship between GFR and 24 h urinary salt in salt
      sensitive patients did not differ from that in salt resistant patients. The GFR
      response to salt loading was largely independent of the renin-aldosterone system.
      No change in arterial pressure nor in GFR was observed in healthy subjects. At
      fixed protein intake, changes in salt intake in the physiological range are
      associated with important GFR variations in mild hypertensives. As long as
      hyperfiltration in mild hypertension is a predictor of renal function
      deterioration, high salt intake, independent of the effect of arterial pressure,
      could be a factor that contributes to nephronic obsolescence in patients with
      essential hypertension.

PMID- 8733033
TI  - Reproducibility of the circadian blood pressure fall at night in healthy young
      volunteers.
AB  - The aim of this study was to evaluate the reproducibility of the circadian blood
      pressure (BP) change in normal healthy volunteers. The subjects were 32 healthy,
      young, normotensive volunteers who underwent 24 h ambulatory BP monitoring on two
      occasions, at least 4 weeks apart. Data were analysed using standard definitions
      of day and night (i.e. 07.00-22.00 for daytime and 22.00-07.00 for night time),
      event diaries to identify individual's day and night time and a time independent
      method (cusum analysis). Intraindividual variations of BP were assessed using the
      coefficient of variation (CV). The mean 24 h BP was very reproducible with a CV
      of 4.7%. Using the fixed definition of day and night, mean night time systolic
      blood pressure (SBP) was significantly reduced on the second visit compared to
      the first (P < 0.001). Using fixed times for day and night, day-night difference
      was poorly reproducible, with a CV of 52% for SBP and 59% for diastolic blood
      pressure (DBP), however this improved using diary based day-night to 40/41% and
      cusum analysis to 24.6/28.1%. We recommend that circadian BP changes are studied
      using individual definitions of day and night or time independent methods such as
      cusum analysis.

PMID- 8733034
TI  - I/D polymorphism of the angiotensin-converting enzyme gene does not predict
      isolated systolic or systolic-diastolic hypertension in the elderly.
AB  - To determine whether insertion/deletion (I/D) polymorphism (intron 16) of the
      angiotensin converting-enzyme (ACE) gene is associated with isolated systolic
      hypertension (ISH: systolic blood pressure (BP) > or = 160, diastolic BP < 90 mm
      Hg) or systolic-diastolic hypertension (S-D hypertension: diastolic BP > or = 90
      +/- systolic BP > or = 160 mm Hg) compared with normotensive controls (systolic
      BP < 160, diastolic BP < 90 mm Hg), we conducted a case-control study of 733 non
      institutionalised, elderly (> or = 60 years) residents of Dubbo, NSW. Individuals
      were classified as: ISH (n = 167), S-D hypertension (n = 207) and normotensive
      control (n = 359) with age and sex matching. II, DD and ID genotypes were
      determined by a nested PCR strategy using DNA extracted from serum. The
      frequencies of D and I alleles in the control population (0.70 and 0.30
      respectively) were not significantly different in the ISH group or the S-D
      hypertension group (chi 2: 1.7, P = 0.42). After adjustment for several potential
      confounders, neither genotype nor allele predicted ISH (II vs DD: odds ratio
      (OR): 1.06, 95% confidence interval (CI): 0.55-2.03; I vs D: 1.09, 0.82-1.46) or
      S-D hypertension (II vs DD: 1.19, 0.67-2.10; I vs D: 1.16, 0.89-1.52) in this
      elderly cohort. The I/D polymorphism of the ACE gene is not a marker for either
      form of hypertension in this large elderly sample.

PMID- 8733035
TI  - Correlation between peripheral hemodynamic changes and left ventricular diastolic
      function in hypertensive patients treated with urapidil.
AB  - We evaluated the modifications induced by chronic treatment with an alpha 1
      adrenolytic hybrid drug, urapidil, on the hemodynamic parameters in peripheral
      artery and left ventricle diastolic function. Fifteen mild to moderate essential
      hypertensive patients (13 men, 2 women; mean age 42 years, range 32-54 years)
      received urapidil (60 mg b.i.d.) for 6 months. Peripheral hemodynamic and cardiac
      parameters were evaluated by duplex scanner, coupled with a plethysmographic
      method, basally (T0) and after 6 weeks' (T1) and 6 months' treatment (T2). Mean
      blood pressure (BP) showed a reduction after 6 weeks of -9.07 mm Hg (confidence
      intervals [CI] 95%: -9.21; -8.92; P < 0.01), which was maintained after 6 months
      (-8.21 mm Hg, CI 95%: -8.97; -7.43; P < 0.01), while no significant change was
      seen in heart rate. Compliance showed highly significant changes after both 6
      weeks (+1.073 dyn-1.cm4.10(-7), 95% CI: +0.965; +1.181, P < 0.001) and 6 months
      (+0.933 dyn-1.cm4. 10(-7), 95% CI: +0.903; +0.963, P < 0.001), as well as
      characteristic impedance (T1:-16.689 dyn.s.cm-5/10(2), 95% CI: -16.914; -16.463 P
      < 0.001; T2: -15.98 dyn.s.cm-5. 10(2), 95% CI: -18.186; -13.784; P < 0.001) and
      forearm resistances (T1: -26.153 mm Hg.ml-1.s, 95% CI: -34.553; -17.753, P <
      0.01; T2: -43.587 mm Hg.ml-1.s, 95% CI: -52.711; -34.464, P < 0.01). Similarly,
      we have recorded a similar change in left ventricular end-diastolic posterior
      wall thickness (T1: -1.067 mm, 95% CI: -1.099; -1.035, P < 0.01; T2: -2.866 mm,
      95% CI: -3.044; -2.688, P < 0.01), end-diastolic interventricular septum
      thickness (T1: -0.921 mm, 95% CI: -1.511; -0.289, P < 0.05; T2: -2.711 mm, 95%
      CI: -3.211; -2.199, P < 0.01), end-diastolic volume (T1: +6.4 ml, 95% CI: +6.343;
      +6.456, P < 0.01; T2: +19.867 ml, 95% CI: +18.564; +21.170, P < 0.01), and
      mass/volume index (T1: -0.11, 95% CI: -0.118; -0.101, P < 0.01; T2: -0.218, 95%
      CI: -0.221; -0.217, P < 0.01). Changes in arterial compliance have shown a
      statistically significant correlation with changes in mass/volume index (r = 
      0.468; P < 0.03), end diastolic volume (r = 0.501; P < 0.02), as well as left
      ventricle rapid filling phase (r = 0.426; P < 0.05) and left ventricle end
      diastolic posterior wall thickness (r = -0.478, P < 0.03). Our results suggest
      that the antihypertensive efficacy of urapidil coupled with the restoration of
      the dumping function of the large arteries, and the reduced activation of reflex
      sympathetic activation, may play a considerable role among the mechanisms
      allowing the regression of the functional modifications affecting the left
      ventricular diastole.

PMID- 8733036
TI  - Effects of antihypertensive therapy on platelet cytosolic calcium responses to
      low density lipoprotein cholesterol.
AB  - This study examines the effects of antihypertensive therapy on platelet cytosolic
      calcium [Ca2+]i responses to low-density lipoprotein cholesterol (LDL) and
      vasopressin (AVP) in 15 patients (50-80 years) participating in the Hypertension
      Optimal Treatment International Study. All patients (diastolic blood pressure
      (DBP) > or = 100 mm Hg and < or = 115 mm Hg) were treated with the calcium
      antagonist felodipine (10 mg p.o.) with or without addition of enalapril (up to
      20 mg daily as needed) to lower diastolic pressures to < 85 mm Hg. This
      antihypertensive therapy lowered DBP (104 +/- 0.8 to 78 +/- 1.6 mm Hg, P <
      0.0001), but had no effect on basal [Ca2+]i or AVP-stimulated [Ca2+]i responses.
      Basal platelet [Ca2+]i following antihypertensive therapy (49 +/- 3.4 ng/ml) were
      not different from those prior to therapy (52 +/- 4.7 ng/ml). Additionally,
      [Ca2+]i responses to AVP following therapy (554 +/- 74 units) were not different
      from those prior to treatment (595 +/- 49 units). Following antihypertensive
      therapy, [Ca2+]i responses to 200 micrograms/ml of LDL were decreased fourfold (P
      < 0.05). These results suggest that antihypertensive therapy with a calcium
      channel blocker may potentially impact the atherogenic process by reducing the
      platelet [Ca2+]i rise, and potentially the aggregatory response, to LDL.

PMID- 8733037
TI  - Pattern recognition of loss of early systolic peak by Doppler ultrasound has a
      low sensitivity for the detection of renal artery stenosis.
AB  - In a group of 57 hypertensive patients seen in the out-patient department, the
      authors did a prospective study to the value of pattern recognition of changes in
      early systolic peak by Doppler ultrasound (DU) in the examination of renal
      arteries, as compared with intra-arterial digital subtraction angiography. In
      five patients (8.7%) DU resulted in technical failure, in one because of the
      inability to hold breath long enough, in one because the Doppler signals from one
      part of the kidney were unclear and in three because overlying adipose tissue
      hindered the examination. Among the remaining 52 patients, 13 had unilateral and
      six bilateral stenoses greater than 50% of the luminal surface on angiography. By
      DU 10 patients with a stenosis were identified, one of which was a false positive
      result. Of the remaining nine, six patients had a unilateral stenosis and three a
      bilateral stenosis that was identified as unilateral by ultrasound. Therefore,
      none of the bilateral stenosis was identified as such by DU. Thus, for the
      detection of renal artery stenoses greater than 50% visual waveform analysis of
      DU signals has a sensitivity of 47% and a specificity of 97%. The conclusion is
      therefore that the DU procedure employed in this study has a limited value in the
      examination of the renal arteries of hypertensive patients with the aim to detect
      renal arterial stenosis.

PMID- 8733038
TI  - Greater reduction of urinary albumin excretion in hypertensive type II diabetic
      patients with incipient nephropathy by lisinopril than by nifedipine.
AB  - A double-blind, randomised, parallel group, multicentre, multinational study
      compared the effects of 12 months' treatment with lisinopril (10-20 mg once
      daily) or nifedipine retard tablets (20-40 mg twice daily) in 239 males (aged 18
      75 years) and 96 post-menopausal females (aged 40-75 years). They all had a
      history of clinically stable type II diabetes > 3 months, microalbuminuria and
      early diabetic nephropathy (a urinary albumin excretion (UAE) rate ranging from
      20 to 300 micrograms/min) and a sitting diastolic blood pressure (DBP) 90-100 mm
      Hg (Korotkoff phase V) inclusive at both entry and after 3-4 weeks' placebo
      treatment. The aim of treatment was to achieve a reduction in sitting DBP to < 90
      mm Hg 24-30 h after the last dose of lisinopril or 12-18 hours after the last
      dose of nifedipine and to evaluate the effect of these treatments on UAE over 12
      months. The effect of the two treatments on ambulatory blood pressure (BP) was
      also evaluated in a subset of patients. Management of diabetes with oral
      hypoglycaemic drugs, diet and insulin alone or in combination was permitted.
      Median UAE fell on lisinopril from 65.5 (range 20-297) micrograms/min at baseline
      to 39.0 (2-510) micrograms/min after 12 months. On nifedipine median UAE fell
      from 63.0 (range 20-289) micrograms/min at baseline to 58.0 (9-1192)
      micrograms/min after 12 months. The estimated median difference between the
      effects of the two treatments was 20 micrograms/min (P = 0.0006). Over 12 months
      both treatments produced similar falls in sitting BP from 163 +/- 17/99 +/- 6 mm
      Hg (mean +/- s.d.) to 147 +/- 18/88 +/- 10 mm Hg for lisinopril and from 161 +/-
      18/97 +/- 5 mm Hg to 150 +/- 18/88 +/- 9 mm Hg for nifedipine. Ambulatory BP was
      assessed in a subset of patients and using areas under the BP-time curve (AUC) a
      comparison of the effects of the two treatments showed no between-treatment
      differences. Creatinine clearance, glycaemic control (HbA1c) and lipid profiles
      did not change significantly during either treatment. Frequency of withdrawals
      and adverse events were similar for both treatments. We conclude that lisinopril
      has a significantly more beneficial effect on UAE than nifedipine despite similar
      effects on both BP and glycaemic control in type II diabetic patients with
      hypertension.

PMID- 8733039
TI  - A study of the efficacy of felodipine given once or twice daily in the management
      of elderly hypertensive patients.
AB  - The use of medication given once daily in clinical practice may lead to
      inadequate control of blood pressure (BP) over 24 h because medication is
      frequently titrated at the time of peak effect. Twenty-three patients aged 65-84
      completed a study in which they received placebo, felodipine 2.5 mg once daily,
      felodipine 2.5 mg 12-hourly, and felodipine 5 mg once daily in a randomized,
      double-blind crossover design. BP response was assessed in the clinic 24 h after
      medication and by 24 h ambulatory monitoring. The trough/peak ratio was defined
      as the fall in BP in the 23rd and 24th hour post dose divided by the fall in BP
      in the 3rd and 4th hour post dose. BP fell with all three regimes and the clinic
      BPs did not differ from each other but were lower than placebo. Peak BP responses
      from the ambulatory BP monitor recording were similar with each dose but a
      greater percentage of the effect was maintained prior to the morning dose with
      2.5 mg 12 hourly and 5 mg once daily. Felodipine 2.5 mg once daily reduces BP and
      in some people this effect persists for 24 h. However if this dose is used BP
      should be measured prior to the dose of the drug to ensure that 24 h control is
      maintained. Felodipine 5 mg once daily and felodipine 2.5 mg b.d. were equally
      effective at maintaining control and there was no significant advantage in using
      the twice daily regime. If felodipine 5 mg once daily or higher doses are used BP
      can be titrated post dose with the knowledge that more than 75% of the effect
      will still be present prior to the next dose of the drug. Thus once daily
      felodipine extended release (ER) 5 mg or more can be used effectively to maintain
      BP control over 24 h in clinical practice. In some elderly patients felodipine ER
      2.5 mg once daily is an adequate regime.

PMID- 8733040
TI  - Decreased blood viscosity and serum levels of erythropoietin after anti
      hypertensive treatment with amlodipine or metoprolol: results of a cross-over
      study.
AB  - The increased viscosity of blood of hypertensive patients can be assumed to be a
      risk factor for the development of cardiovascular diseases. The aim of the
      present study was to elucidate whether anti-hypertensive treatment has any impact
      on blood rheology. Twenty patients with previously untreated hypertension who
      consecutively attended our outpatient hypertension clinic were included in this
      prospective, open, cross-over study. The patients were randomly selected to
      treatment with amlodipine or metoprolol. The anti-hypertensive therapy was
      switched after 4 months. Haemorheological and haemodynamic variables were
      measured with rotational viscometry and impedance cardiography, respectively.
      Fifteen and 16 patients could be evaluated after amlodipine or metoprolol
      treatment respectively. The mean blood pressure (BP) decreased from 159 +/-
      22/105 +/- 7 to 139 +/- 21/91 +/- 6 mm Hg on amlodipine and from 162 +/- 22/104
      +/- 5 to 145 +/- 24/90 +/- 8 mm Hg on metoprolol therapy. After amlodipine
      treatment, the total peripheral resistance index decreased whereas metoprolol
      treatment was accompanied by a decrease in the cardiac index. Decreases in whole
      blood viscosity, haematocrit and serum erythropoietin were found after amlodipine
      as well as metoprolol treatment. After amlodipine the plasma viscosity decreased
      and the erythrocyte deformability increased in the majority of patients. Plasma
      fibrinogen decreased after metoprolol treatment. Despite the differences in
      haemodynamic mechanisms underlying the decrease in BP, amlodipine and metoprolol
      exert beneficial effects on blood viscosity. Haemodilution and a decrease in
      serum erythropoietin may be factors underlying this decrease in blood viscosity.

PMID- 8733041
TI  - Localisation of two candidate genes for mental retardation using a YAC physical
      map of the Xq21.1-21.2 subbands.
AB  - Genetic studies in families with X linked mental retardation have suggested the
      location of several MR genes in the human q21 region. Since the establishment of
      cloned resources is an essential step towards the cloning of genes involved in
      inherited diseases, we built a yeast artificial chromosome (YAC) contig and an
      STS map of this part of the X chromosome. The contig, which extends from PGK1 in
      Xq13.3 to DXS1002 in Xq21.2, consists of 30 YACs mapped with 21 markers and spans
      about 6 Mb. The YAC contig was used as a framework to localise several previously
      known genes and CEPH/Genethon polymorphic markers, as well as to construct a
      physical map of the region surrounding one of these genes. We recently localised
      a presumed MR locus to the region flanked by DXS233 (proximal) and CHM (distal).
      In the present work, the zinc finger gene, ZNF6, has been shown to lie within
      this region and to be highly expressed in brain, making it a good candidate MR
      gene. Similarly the VDAC1 gene has been mapped between DXS986 and DXS72 and its
      candidate gene status for the Allan-Herndon-Dudley syndrome is discussed.

PMID- 8733042
TI  - Mutation analysis in 24 French patients with glycogen storage disease type 1a.
AB  - Both alleles of 24 French glycogen storage disease type 1a patients were
      sequenced: 14 different mutations allowed the identification of complete
      genotypes for all the patients. Nine new gene alterations are reported. Five
      mutations, Q347X, R83C, D38V, G188R, and 158 del C, account for 75% of the
      mutated alleles. These data show that the molecular pathology of the glucose-6
      phosphatase gene is heterogeneous in this population. Complete genotyping of the
      index case by systematic sequencing is necessary to allow prenatal diagnosis in
      chorionic villi for at risk couples.

PMID- 8733043
TI  - Direct detection of 4q35 rearrangements implicated in facioscapulohumeral
      muscular dystrophy (FSHD).
AB  - The p13E-11 probe has been shown to detect DNA rearrangements in sporadic and
      familial cases of FSHD. Its use, however, has been hampered by the fact that it
      detects at least two pairs of EcoRI alleles, one derived from the 4q35 region
      (D4F104S1), the other from 10q26 (D10F104S2). We have cloned p13E-11 EcoRI
      fragments from the 4q35 and 10q26 subtelomeric regions and shown the presence of
      several restriction site differences within the KpnI tandem repeat units. The two
      loci present a different distribution of restriction sites for the enzyme BlnI
      which allows differential cleavage of the KpnI units derived from 10q26, leaving
      intact the 4q35 pair of alleles. This method of differential restriction greatly
      facilitates the interpretation of Southern blots obtained from affected and
      unaffected subjects, with an important improvement in reliability for diagnosis
      and genetic counselling. In addition, this method can be used to investigate the
      molecular mechanism of the 4q35 rearrangement implicated in the disease and to
      ascertain whether the rearrangement is because of interchromosomal exchange
      between 4qter and 10qter KpnI repeats.

PMID- 8733044
TI  - Monosomy of distal 4q does not cause facioscapulohumeral muscular dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary neuromuscular
      disorder transmitted in an autosomal dominant fashion. FSHD has been located by
      linkage analysis in the most distal part of chromosome 4q. The disease is
      associated with deletions within a 3.2 kb tandem repeat sequence, D4Z4. We have
      studied a family in which an abnormal chromosome 4 segregates through three
      generations in phenotypically normal subjects. This chromosome is the derivative
      of a (4;D or G) (q35;p12) translocation. Molecular analysis of the region 4q35
      showed the absence of the segment ranging from the telomere to locus D4F104S1.
      Probe p13E-11 (D4F104S1), which detects polymorphic EcoRI fragments containing
      D4Z4, in Southern blot analysis showed only one allele in the carriers of the
      abnormal chromosome 4. Probe p13E-11 EcoRI fragments are contained in the
      subtelomeric region of 4q and their rearrangements associated with FSHD suggested
      that the gene responsible for the muscular dystrophy could be subject to a
      position effect variegation (PEV) because of its proximity to subtelomeric
      heterochromatin. The absence of the 4q telomeric region in our phenotypically
      normal cases indicates that haploinsufficiency of the region containing D4Z4 does
      not cause FSHD.

PMID- 8733045
TI  - Direct molecular diagnosis of CYP21 mutations in congenital adrenal hyperplasia.
AB  - The majority of congenital adrenal hyperplasia (CAH) cases arise from mutations
      in the steroid 21-hydroxylase (CYP21) gene. Without reliance on HLA gene linkage
      analysis, we have developed primers for differential polymerase chain reaction
      (PCR) amplification of the CYP21 gene and the non-functional CYP21P gene. Using
      the amplification created restriction site (ACRS) approach for direct mutational
      detection, a secondary PCR was then performed using a panel of primers specific
      for each of the 11 known mutations associated with CAH. Subsequent restriction
      analysis allowed not only the detection but also the determination of the
      zygosity of the mutations analysed. Existing deletion of the CYP21 gene could
      also be detected. In the analysis of 20 independent chromosomes in 11 families of
      CAH patients in Taiwan, four CYP21 mutation types, besides deletion, were
      detected. Interestingly, in five different alleles, the CYP21P pseudogene
      contained some polymorphisms generally associated with the CYP21 gene. These
      results suggest gene conversion events that are occurring in both CYP21P and
      CYP21 genes. Our combined differential PCR-ACRS protocol is simple and direct and
      is applicable for prenatal diagnosis of CAH using chorionic villi or amniotic
      cells.

PMID- 8733046
TI  - FMR1 fully expanded mutation with minimal methylation in a high functioning
      fragile X male.
AB  - Cytogenetic and molecular genetic analysis of a peripheral blood sample from a 31
      year old, non-mentally retarded male with a family history of fragile X syndrome
      showed unexpected results. Nine percent of cells evaluated cytogenetically
      expressed a fragile X chromosome and molecular examination of the FMR1 gene
      showed a highly unusual pattern defined as a minimally methylated fully expanded
      mutation. This case illustrates the need to recognise exceptional variations of
      fragile X syndrome mutations.

PMID- 8733047
TI  - First experiences with genetic counselling based on predictive DNA diagnosis in
      hereditary glomus tumours (paragangliomas).
AB  - Hereditary glomus tumour (MIM 168,000) or paraganglioma (PGL) is a slowly
      progressive disorder causing benign tumour growth predominantly in the head and
      neck region. Though benign in nature the tumours can lead to severe morbidity.
      Inheritance of PGL is autosomal dominant and is strongly modified by genomic
      imprinting; only a paternally transmitted PGL gene leads to symptoms. A gene for
      PGL has recently been mapped to 11q22.3-q23. Genetic counselling on the basis of
      DNA linkage diagnosis was offered in an extended Dutch pedigree. Thirty-two
      subjects opted for further counselling, of whom 20 applied for DNA testing and
      participated in a standardised protocol. Sixteen cases had presymptomatic testing
      (paternal allele); four of these appeared to have the at risk haplotype and in
      two of them a glomus tumour was subsequently detected on MRI. In one case linkage
      results were inconclusive (recombination) and one person did not want to learn
      his test result. Four cases had testing for carrier status (maternal allele) of
      which one appeared to be a carrier. Our data show that genetic counselling gains
      significant accuracy when based on parent of origin, sex of the counsellee, and
      DNA linkage diagnosis. Moreover, a normal DNA result may prevent unnecessary
      worry and investigations, while an established presymptomatic diagnosis will
      guide adequate clinical management. The psychological impact of counselling and
      predictive DNA testing is unclear as yet. Further investigations into the natural
      history of PGL in gene carriers and into the psychological impact of DNA testing
      is desirable.

PMID- 8733048
TI  - A novel deletion at codon 441 of the APC gene associated with ophthalmic lesions
      (CHRPE) in a South African family.
AB  - A novel mutation at codon 441 in exon 10 of the adenomatous polyposis coli (APC)
      gene was identified in a South African family of mixed ancestry, using a
      convenient, non-radioactive, heteroduplex-SSCP screening assay. This single
      thymidine deletion after nucleotide position 1322 creates a frameshift resulting
      in a downstream stop codon at amino acid residue 453 of the APC gene. Genotypes
      of nine family members were subsequently correlated with the presence or absence
      of congenital hypertrophy of the retinal pigment epithelium (CHRPE), since
      expression of this common extracolonic manifestation of FAP is largely determined
      by the length of the truncated protein. CHRPE was absent in the five unaffected
      family members analysed, while four mutation positive subjects showed these
      ophthalmic lesions. Correlation between the molecular analysis and ophthalmic
      examinations, performed without knowledge of clinical and genetic status
      respectively, provided additional evidence in favour of the view that the range
      of phenotypic expression in FAP may result from different allelic manifestations
      of APC mutations.

PMID- 8733049
TI  - Cytogenetic and epidemiological findings in Down syndrome, England and Wales 1989
      to 1993. National Down Syndrome Cytogenetic Register and the Association of
      Clinical Cytogeneticists.
AB  - Data from the National Down Syndrome Cytogenetic Register is used to describe the
      cytogenetics and epidemiology of registered cases. The register comprises
      notifications from cytogenetics laboratories in England and Wales. This report is
      of 5737 cases registered between 1989 and 1993: 2169 prenatal and 3436 postnatal
      diagnoses, and 132 spontaneous abortions. Eighty eight registrations were from
      multiple pregnancies. Ninety five percent had regular trisomy 21. In 4% there was
      a translocation, mostly Robertsonian t(14;21) or t(21;21). One percent were
      mosaics with one normal cell line. Mean maternal age was raised in free trisomy
      21, but not in translocations. Where families had been investigated, about a
      third of translocations were inherited, six to seven times more often from the
      mother than the father. Associations between free trisomy 21 and structural
      chromosomal defects in the births were no more common than expected from newborn
      series. The overall sex ratio was raised (male to female: 1.23 to 1), and there
      was an excess of associated male sex chromosomal aneuploidy. However, in mosaics
      with one normal cell line the male to female ratio was 0.8 to 1, and in twins
      discordant for trisomy 21 there was also a female excess.

PMID- 8733050
TI  - Breakpoints in alpha, beta, and satellite III DNA sequences of chromosome 9
      result in a variety of pericentric inversions.
AB  - Human chromosome 9 with a pericentric inversion involving the qh region is
      considered normal. It has probably evolved through breakage and reunion and is
      retained through mendelian inheritance without any apparent phenotypic
      consequences. Fluorescent in situ hybridisation (FISH) technique using alpha,
      beta, and satellite III DNA probes showed that the breakpoints are variable and
      can be localised in the alpha or in the satellite III and beta DNA regions or
      both. Three types of inversions are proposed which appear similar by CBG banding:
      pericentric inversions with two alphoid, one beta, and one satellite III
      hybridisation signals were classified as type A. Type B were those with two beta,
      one alpha, and one satellite III hybridisation signals, while type C was complex,
      and most likely involved two inversions, since two separate hybridisation signals
      were detected in each of the alphoid, beta satellite, and satellite III DNA
      regions. Based on eight cases, type A is likely to be the most frequent, but the
      frequencies, which at present appear non-random for these different types of
      inversions in the population, can only be estimated by studying a larger sample
      size. Inversion heteromorphisms may promote reshuffling of tandem arrays of DNA
      repeat sequences, thereby giving rise to new heteromorphic domains.
      Alternatively, the repetitive nature of the sequences lends to the structural
      variations observed within the inv(9) chromosomes (or any other abnormal
      chromosome that is the result of recombination between, or breakage within,
      repetitive DNA).

PMID- 8733051
TI  - Small extra ring chromosome derived from chromosome 10p: clinical report and
      characterisation by FISH.
AB  - We present a case with a small extra ring chromosome which was found in 66% of
      lymphocytes on routine cytogenetic examination. FISH analyses, using centromere
      specific and single copy probes, showed that the extra ring chromosome was
      derived from the most proximal part of 10p, close to the centromere. The patient
      has a unilateral cleft lip and palate, mild dysmorphic features, and mild mental
      retardation. Only a limited number of extra ring chromosomes have been
      characterised so far. To our knowledge, this is the first reported patient with
      an extra ring chromosome derived from chromosome 10p.

PMID- 8733052
TI  - Marfan syndrome.

PMID- 8733053
TI  - Renal-hepatic-pancreatic dysplasia: an autosomal recessive malformation.
AB  - We report two brothers with a cystic malformation of the kidneys, liver, and
      pancreas. In both cases the malformation was fatal and the children died shortly
      after birth. The pathological findings, consisting of multicystic dysplastic
      kidneys, dilated and dysgenetic bile ducts, dilated pancreatic ducts, and
      polysplenia, correspond to those reported by Ivemark as renal-hepatic-pancreatic
      dysplasia. Many polymalformation syndromes include cystic affectation of these
      three organs, so this syndrome could be an isolated entity or a final common
      pathway of response of these organs to a variety of developmental disturbances,
      which could also include splenic abnormalities. We propose an autosomal recessive
      pattern of inheritance for renal-hepatic-pancreatic dysplasia.

PMID- 8733054
TI  - Arginine-164-tryptophan substitution in connexin32 associated with X linked
      dominant Charcot-Marie-Tooth disease.
AB  - A Spanish family with X linked dominant Charcot-Marie-Tooth (CMTX1) neuropathy
      was screened for point mutations in the connexin32 gene (GJ beta 1). The patients
      showed a C-T transition at position 552 which predicts arginine to tryptophan
      substitution at amino acid 164 (R164K). This mutation destroys an AciI
      restriction site at position 552 and creates a PflMI restriction site.

PMID- 8733055
TI  - Orocardiodigital syndrome: an oral-facial-digital type II variant associated with
      atrioventricular canal.
AB  - We report on a patient with a constellation of anomalies including hamartomas of
      the tongue, polysyndactyly, and atrioventricular canal. A similar association has
      been previously described by Orstavik et al in two sibs. The clinical spectrum of
      the oralfacial-digital syndrome (OFDS) type II includes all these features. In
      particular, congenital heart defect, mainly atrioventricular canal, has been
      described in a few cases. It has been previously suggested that these latter
      patients may be affected by a variant of OFDS type II. We propose to distinguish
      this orocardiodigital variant and point out the association of the syndrome with
      atrioventricular canal.

PMID- 8733056
TI  - Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing
      loss (CAPOS): a new syndrome.
AB  - There are a large number of well recognised syndromes comprising cerebellar
      ataxia in association with other neurological features. We report three family
      members who presented with a relapsing, early onset cerebellar ataxia, associated
      with progressive optic atrophy and sensorineural deafness. All three patients
      have areflexia (in the absence of a peripheral neuropathy), a pes cavus
      deformity, and show varying degrees of severity. Extensive neurological
      investigations have been normal, and the aetiology and pathophysiology of this
      disorder remain unclear. This may represent a separate syndrome of early onset
      cerebellar ataxia with associated features ("cerebellar ataxia plus"), which is
      likely to either have an autosomal dominant or maternal mitochondrial pattern of
      inheritance. The recognition of this association under the acronym of CAPOS
      (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural
      deafness) may help in the delineation of a new syndrome.

PMID- 8733057
TI  - A boy with developmental delay and a maternally inherited deletion in 15q11q13.
AB  - A boy was referred at 8 weeks of age for failure to thrive. Cytogenetic and
      molecular studies showed that he had a large proximal deletion of the maternally
      derived chromosome 15q. He did not have Angelman syndrome, but at 2 years of age
      was severely globally delayed. He died at 2 1/2 years of age.

PMID- 8733058
TI  - Mirror hands and feet: a further case of Laurin-Sandrow syndrome.
AB  - We report a girl with mirror hands and feet and associated groove of the nasal
      columella. She represents only the sixth reported case of this spectrum of
      congenital anomalies,first reported by Laurin and Sandrow.

PMID- 8733059
TI  - A new case of fibrochondrogenesis from Spain.
AB  - A rare, neonatally lethal chondrodysplasia with histological characteristics was
      first described in 1978 and the authors named the condition fibrochondrogenesis.
      Here we report the eighth published case of fibrochondrogenesis. This was
      identified in a population of 1,158,067 consecutive livebirths, so we can assume
      that this figure should be the minimal prevalence for livebirths.

PMID- 8733060
TI  - Linkage analysis of two Canadian families segregating for X linked
      spondyloepiphyseal dysplasia.
AB  - X linked spondyloepiphyseal dysplasia (SED) is caused by a growth defect of the
      vertebral bodies leading to characteristic changes in the vertebral bodies and a
      short trunk. The gene responsible for this disorder has previously been mapped to
      Xp22, with a maximum likelihood location between markers DXS16 and DXS92. We
      present linkage data using microsatellite markers on two Canadian X linked SED
      families, one of Norwegian descent and the other from Great Britain. In the Xp22
      region, three recombination events have occurred in these families, two between
      markers DXS996 and DXS1043 and one between DXS999 and DXS989. One family shows a
      maximal lod score of 3.0 at theta = 0 with marker DXS1043 and the other family
      has a maximal lod score of 1.2 at theta = 0 with markers DXS1224 and DXS418. Both
      families therefore support the previously reported gene localisation.

PMID- 8733061
TI  - Analysis of GLRA1 in hereditary and sporadic hyperekplexia: a novel mutation in a
      family cosegregating for hyperekplexia and spastic paraparesis.
AB  - Hyperekplexia is a rare condition characterised by the presence of neonatal
      hypertonia and an exaggerated startle response. Mutations have been described in
      GLRA1, the gene encoding the alpha 1 subunit of the glycine receptor, in dominant
      families with hyperekplexia and in a single sporadic case, thought to represent
      an autosomal recessive form of the disease. In this study the coding region of
      the GLRA1 was analysed in eight probands with hyperekplexia by restriction digest
      and sequencing. Two familial cases were found to possess the previously described
      G1192A (R271Q) mutation in exon 6. In an additional family in which hyperekplexia
      cosegregates with spastic paraparesis, a novel A to G transversion at nucleotide
      1206 in exon 6 was detected that changes a lysine at amino acid 276 to a
      glutamate (K276E). In four sporadic cases no mutations were found. In addition,
      one familial case did not have a mutation in the coding region of the gene.

PMID- 8733062
TI  - Acute intermittent porphyria caused by defective splicing of porphobilinogen
      deaminase RNA: a synonymous codon mutation at -22 bp from the 5' splice site
      causes skipping of exon 3.
AB  - Acute intermittent porphyria (AIP) results from mutations in the porphobilinogen
      deaminase (PBG) gene. Three of 14 randomly selected, unrelated patients with the
      cross reacting immunological material (CRIM) negative form of AIP were found to
      have previously undescribed RNA splicing defects. Defective splicing of exons 12
      and 13 was caused by a C-->G transversion at position -3 of the 3' splice site of
      intron 11 and a G-->A transition at the first position of intron 13,
      respectively. Defective splicing of exon 3 was associated with a synonymous codon
      mutation (CGC-->CGG, R28R) at position -22 from the 5' splice site. Our findings
      are consistent with previous reports indicating that about 15% of mutations in
      the PBG deaminase gene that cause AIP affect RNA splicing and add to the evidence
      that synonymous intraexonic codon mutations may cause disease.

PMID- 8733063
TI  - Different origins of mutations at the Machado-Joseph locus (MJD1)

PMID- 8733064
TI  - Pathophysiological targets for beta-blocker therapy in congestive heart failure.
AB  - The treatment of congestive heart failure has seen considerable changes: while
      treatment with diuretics, digitalis glycosides and vasodilators has remained the
      mainstay of therapy, recently neurohumeral inhibition has been developed as an
      important principle: ACE-inhibitors have been shown to significantly improve
      quality of life and exercise performance and to substantially reduce mortality.
      Beta-blockers have been employed with increasing success mainly in congestive
      heart failure due to dilated idiopathic cardiomyopathy, in which a significant
      improvement in symptoms and life expectancy has been demonstrated. However, the
      precise mechanisms by which beta-blockade improves congestive heart failure
      remain to be elucidated. In addition to direct sympathoadrenal inhibition,
      reduction of heart rate may also play a major role in the therapeutic efficacy of
      beta-blockade in congestive heart failure. In the normal human heart increase in
      heart rate is accompanied by an increase in myocardial contractile performance
      (Bowditch-Treppe phenomenon). In chronic heart failure the myocardium undergoes a
      phenotype change which includes alterations of the activity of enzymes regulating
      calcium homoeostasis. The sarcoplasmic reticulum calcium ATPase (SERCA) is
      depressed both in function, as well as in expression. At the same time the
      sarcolemmal sodium-calcium exchanger is increased both in function and in
      expression. The result is a characteristic change in calcium homoeostasis with
      decreased diastolic uptake of calcium into the sarcoplasmic reticulum with
      subsequently reduced calcium release during the next systole, resulting in
      reduced contractile performance. At the same time increased capacity of the
      sodium-calcium exchanger extrudes intracellular calcium ions to the extra
      cellular space, thereby rendering these ions unavailable for the contractile
      cycle. A result of these, seemingly specific, phenotype changes is an alteration
      of the force/frequency relationship. Instead of increasing force of contraction
      with increasing heart rates, in the chronically failing myocardium the
      contractile performance declines with increasing heart rates and only improves
      with decreasing rates. Optimal performance can be seen at heart rates as low as
      30 beats.min. Studies employing photoluminescence markers of free cytosolic
      calcium, such as aequorin, have shown that there is a direct correlation between
      free cytosolic calcium and contractile performance at different levels of heart
      rate. It is likely, therefore, that the heart rate reduction with beta-blockade
      may provide the major explanation for the therapeutic benefits of beta-blockade
      in chronic congestive heart failure.

PMID- 8733065
TI  - Cardiac adrenergic receptor effects of carvedilol.
AB  - Carvedilol is an adrenoceptor antagonist which modulates the activity not only of
      beta 1 and beta 2 but also of alpha 1 adrenergic receptors present on the cell
      surface membrane of the human cardiac myocyte. In the heart, carvedilol has
      approximately 7 times higher potency for beta 1 and beta 2 adrenoceptors, but in
      the doses 50-100 mg . day-1 used in clinical practice, it is essentially non
      selective. In human myocardial preparations and in cultured heart cells,
      carvedilol has no intrinsic sympathomimetic activity but is able to identify high
      affinity agonist-binding receptors whose pharmacological signature is reduction
      in binding by incubation with guanine nucleotides (guanine nucleotide-modulatable
      binding). This property is more prominent for the human beta 2 than for the beta
      1 adrenoceptor. The property of gaunine nucleotide-modulatable binding for
      carvedilol and structurally related bucindolol correlates with their ability to
      directly down-regulate beta 1-like receptors present in cultured chick myocytes,
      and with a lack of reversal of down-regulation of cardiac beta-receptors in
      patients with heart failure. Carvedilol does not exhibit high levels of inverse
      agonist activity, which may contribute to its good tolerability in subjects with
      heart failure. These data indicate that carvedilol produces a high degree of
      adrenergic receptor blockade in the failing human heart, and does not re
      sensitize the beta-receptor pathway to stimulation by adrenergic agonists.

PMID- 8733066
TI  - Beta-blockers in heart failure--the evidence from clinical trials.
AB  - There are good theoretical reasons for supposing that long-term treatment with a
      beta-blocker would improve symptoms and survival in patients with heart failure.
      A series of small studies have shown that beta-blockers improve haemodynamic
      parameters, but it is well known that these correlate poorly with symptoms. There
      is some evidence that exercise tolerance is also improved. Although there is so
      far no convincing evidence that beta-blockers prolong survival in patients with
      heart failure the development of a new generation of these drugs with additional
      vasodilating properties makes further large studies essential.

PMID- 8733067
TI  - Beta-blockade in the management of chronic heart failure. Another step in the
      conceptual evolution of a neurohormonal model of the disease.
AB  - Although heart failure has been viewed primarily as a haemodynamic disorder, the
      development of pharmacologic agents that address the haemodynamic derangements
      has not proved to be a successful approach to its management. Consequently,
      attention in recent years has shifted to the development of neurohormonal
      antagonists in the hope that prolonged interference with the renin-angiotensin
      system and the sympathetic nervous system would have favourable effects on the
      natural history of heart failure. Both converting-enzyme inhibitors and beta
      adrenergic blockers have been shown to produce long-term haemodynamic and
      clinical benefits in patients with left ventricular systolic dysfunction in
      controlled clinical trials. For both classes of drugs, the improvement evolves
      gradually over several months, although initiation of therapy may be accompanied
      by undesirable (but usually transient) haemodynamic effects. This pattern of
      response contrasts sharply with the response pattern seen with direct-acting
      vasodilators that stimulate neurohormonal systems (e.g. flosequinan). Initiation
      of treatment with flosequinan produces immediate clinical benefits due to the
      haemodynamic actions of the drug, but this improvement may disappear within weeks
      as a result of neurohormonal activation, which also may contribute to the
      increased risk of death seen during long-term administration of the drug.
      Recognition of the prognostic importance of neurohormonal activation has led to
      the hope that long-term treatment with beta-blockers might reduce mortality in
      heart failure in a manner similar to that seen with converting-enzyme inhibitors.
      Large-scale, long-term studies are being planned to evaluate this possibility.

PMID- 8733068
TI  - Carvedilol, a novel vasodilating beta-blocker with the potential for
      cardiovascular organ protection.
AB  - Carvedilol is a vasodilating beta-blocker currently marketed for the treatment of
      mild to moderate hypertension and application is being filed to the FDA for
      treatment of congestive heart failure. Carvedilol reduces peripheral vascular
      resistance by blocking arterial alpha 1-adrenoceptors, thereby producing
      vasodilation, while preventing reflex tachycardia by blocking cardiac beta 1- and
      beta 2-adrenoceptors. In addition to the safety and efficacy of carvedilol as an
      antihypertensive agent, experimental studies indicate that carvedilol also
      provides significant cardioprotection in animal models of acute myocardial
      infarction as well as protection against the vascular remodelling that occurs
      following injury of the vasculature. Recent pharmacological studies have
      uncovered several novel properties of carvedilol which may function to protect
      the heart and vasculature from chronic pathological processes, such as ischaemia,
      atherosclerosis and the remodelling that occurs in the heart and blood vessels as
      a consequence of pressure overload, injury or shear stress. Specifically,
      carvedilol, likely as a result of the carbazol moiety, is a potent anti-oxidant.
      In physicochemical, biochemical and cellular assays carvedilol and several of its
      metabolites inhibit lipid peroxidation, scavenge oxygen free radicals, inhibit
      the formation of reactive oxygen radicals and prevent the depletion of endogenous
      antioxidants, such as vitamin E and glutathione. Moreover, carvedilol blocks the
      oxidation of low-density lipoproteins (LDL), and thereby prevents the formation
      of oxidized-LDL which is believed to stimulate foam cell formation and augment
      the development of atherosclerotic plaque. The ability of carvedilol to prevent
      the formation of oxidized LDL, in addition to the general anti-oxidant properties
      of the compound, results in the protection of the endothelium from oxygen free
      radical injury, and thereby prevents the subsequent events triggered by
      endothelial damage. Recently, carvedilol has also been shown to inhibit vascular
      smooth muscle cell proliferation and migration. Because carvedilol can inhibit
      vascular smooth muscle cell proliferation induced by a wide variety of mitogens
      (e.g. growth factors, angiotensin II, endothelin, thrombin), it is likely that
      the site of inhibition occurs at some point beyond the specific mitogen
      receptors, possibly at a distal common pathway that affects the smooth muscle
      cell cycle. These unique activities of carvedilol have also been confirmed in
      vivo in a rat model of neointimal formation following vascular injury by balloon
      angioplasty, where vascular smooth muscle cell migration and proliferation are
      the key processes involved in the formation of neointima leading to vascular
      stenosis. In this model, carvedilol suppressed neointimal growth to a remarkable
      extent ( > 85% inhibition of neointimal formation) at a dose that is similar to
      the antihypertensive dose used clinically in hypertensive patients. Taken
      together, these unique multiple actions of carvedilol provide not only for
      adequate control of elevated blood pressure, but may also provide for protection
      of the heart and vasculature from secondary damage due to hypertension itself, as
      well as from other causes, such as ischaemia, pressure overload, shear stress,
      vascular injury and atherosclerosis.

PMID- 8733069
TI  - The preventative effects of vasodilating beta-blockers in cardiovascular disease.
AB  - The beta-blocking drugs are known to modify the course of hypertensive and
      atherosclerotic heart disease and significantly reduce the mortality and
      morbidity associated with these diseases. The place of vasodilating beta-blocking
      drugs, of which carvedilol is an example, has not been so clear, although they
      have obvious theoretical advantages. We performed a study on 12 hypertensive
      subjects using the technique of continuous ambulatory intra-arterial blood
      pressure recording which demonstrated that carvedilol (50 mg bid) achieved
      satisfactory blood pressure control throughout the full 24 h cycle. The addition,
      there was a marked reduction in left ventricular end-systolic and end-diastolic
      volumes with prolonged administration, suggesting a decrease in heart size,
      confirmed in other studies. A second study in patients with chronic stable angina
      and impaired left ventricular wall motion showed that carvedilol 25 mg bid not
      only improved exercise tolerance, but also reduced heart size, improved left
      ventricular ejection fraction, and abolished wall motion abnormalities. These
      results prompted a further study in 17 patients with chronic ischaemic heart
      failure. The haemodynamic and clinical responses to intravenous carvedilol
      followed by the oral drug 50 mgm b.i.d. for 8 weeks were studied. There was an
      improvement in all haemodynamic indices, although postural hypotension
      necessitated withdrawing two patients and clinical deterioration was evident in
      two others. The beneficial effects of carvedilol were considered to be related to
      the combined reduction in afterload and inhibition of neurohumeral activation.
      These results have been confirmed in placebo-controlled, double-blind studies
      from other workers.

PMID- 8733070
TI  - Beta-blockers in heart failure. Future directions.
AB  - The rationale for beta-blockade in heart failure is now well established. Heart
      failure mortality, which is predicted by neurohormonal activation, remains high
      despite modern treatment including ACE inhibition, and additional neurohormonal
      blockade has further therapeutic potential. Previous clinical trial experience in
      heart failure, most of which has been in patients with idiopathic cardiomyopathy,
      indicates consistent improvement in ventricular function although variable
      changes in symptoms and exercise performance. However, the major burden of heart
      failure occurs in patients with ischaemic heart disease and in this respect it is
      notable that beta-blockade following myocardial infarction confers significant
      mortality benefit in subgroups with heart failure. The Australia and New Zealand
      carvedilol heart failure study is the largest completed study of beta-blocker
      treatment in patients with heart failure of ischaemic aetiology, including 415
      patients randomized to carvedilol or placebo and indicating excellent
      tolerability of a titrated dose regimen and improved ventricular function after 6
      months of treatment. An overview of all currently available randomized clinical
      trials of beta-blockade in heart failure, which includes more than 1600 patients,
      indicates a mortality risk reduction of approximately 20% but with wide
      confidence intervals. A large scale trial with several thousand patients is
      required to detect reliably a plausible 15-20% mortality reduction with beta
      blockade in heart failure. The dissociation of clinical and mortality effects
      demonstrated with other heart failure treatments indicates the necessity for an
      appropriately powered mortality study which could define a major improvement in
      heart failure therapy for the future.

PMID- 8733071
TI  - Congestive heart failure. Towards a comprehensive treatment.
AB  - Heart failure constitutes an increasing health hazard with major demands on
      health care resources. Recent major advances in drug treatment have yet to be
      translated into increased survival of heart failure patients in the community at
      large. Failure of diagnosis is a major factor in delaying early and adequate
      treatment. Echocardiography probably provides the most reliable and inexpensive
      instrument to confirm the diagnosis and pinpoint the mechanical components of the
      syndrome. The targets for therapeutic intervention may be categorized (i)
      haemodynamic, neuroendocrine and metabolic disorders (ii) symptoms and quality of
      life, (iii) morbidity and mortality risks. Symptoms and quality of life are the
      prime concerns of the physician in the treatment in the individual patient.
      Selection of anti-heart failure drugs used should be based on knowledge of the
      impact on the pathophysiological disorders and on the morbidity and mortality
      risks. Diuretics, vasodilators and ACE-inhibitors are now accepted as standard
      treatment, particularly when used in combination. Controversy continues to
      surround the efficacy of digitalis glycosides; they improve symptoms in some
      patients but their impact on morbidity and mortality risks is still uncertain.
      Even with standard treatments, may practical therapeutic questions remain, one of
      which is what is the most efficacious dose of each anti-heart failure drug which,
      when used in combination, will give the maximum improvement in quality of life
      and greatest extension of survival? Despite available treatment with diuretics,
      digitalis, vasodilators and ACE-inhibitors, the morbidity and mortality risks of
      congestive heart failure remain high. None of these drug groups significantly
      modulates the excessive excitation of the sympathoadrenal system, one of the two
      major neuroendocrine hazards of heart failure. For this reason, amongst the many
      newer drugs in development, the beta-adrenoceptor antagonists hold considerable
      promise as the next step towards a more comprehensive treatment of congestive
      heart failure.

PMID- 8733072
TI  - Calcium antagonism in perspective: new data on diltiazem in unstable angina.

PMID- 8733073
TI  - Three-dimensional echocardiography: the virtual reality in cardiology--luxury or
      useful technique?

PMID- 8733074
TI  - Assessment of myocardial damage in dilated cardiomyopathy.

PMID- 8733075
TI  - Preconditioning of the heart.

PMID- 8733076
TI  - Stress induced T wave normalization: a new marker of myocardial ischaemia.

PMID- 8733077
TI  - Doppler diastolic transmitral ventricular filling patterns--towards a better
      understanding.

PMID- 8733078
TI  - The cost-effectiveness of dual-chamber pacing.

PMID- 8733079
TI  - Too old for heart valve replacement?

PMID- 8733080
TI  - Athletes and arrhythmias: clinical considerations and perspectives.

PMID- 8733081
TI  - The open artery hypothesis: to open, or not to open, that is the question.

PMID- 8733082
TI  - Characterization and identification of women with angina pectoris.

PMID- 8733083
TI  - Cardiovascular risk factors in relation to educational level in 36 000 men and
      women in The Netherlands.
AB  - The study objective was to describe the associations between socioeconomic status
      and (concurrence of) cardiovascular risk factors. The Netherlands Monitoring
      Project on Cardiovascular Risk Factors is a screening project that was carried
      out from 1987-1991 in three cities. Cross-sectional data were obtained on
      educational level and on the prevalence of smoking, alcohol intake, physical
      inactivity, obesity, hypertension, hypercholesterolaemia and low HDL-cholesterol.
      A total of 36 000 men and women, aged 20-59 years participated. For all risk
      factors, except alcohol intake, a significant inverse association was found with
      educational level. Concurrence of risk factors was more prevalent in lower
      educated groups than in higher educated groups, but not more than can be expected
      under the condition of independence of the risk factors (no clustering). In
      conclusion, in the lower educated groups the prevalence of individual risk
      factors and of concurrence of risk factors was higher than in the higher educated
      groups. Concurrence of risk factors can have a synergistic effect on the risk for
      cardiovascular disease. Therefore socioeconomic differences in risk factors may
      explain a greater part of the socioeconomic differences in cardiovascular
      morbidity and mortality than is generally assumed.

PMID- 8733084
TI  - T wave normalization during dobutamine stress testing in patients with non-Q wave
      myocardial infarction. A marker of myocardial ischaemia?
AB  - Conflicting results in a heterogenous patient population have been described on
      the functional significance of stress-induced T wave normalization in the ECG.
      The aim of this study was to evaluate the relationship between T wave
      normalization during dobutamine stress testing and stress-induced ischaemia
      evaluated by echocardiography and myocardial perfusion scintigraphy in patients
      with previous non-Q wave myocardial infarction. Among 520 patients who underwent
      dobutamine stress, testing in conjunction with simultaneous echocardiography and
      201 thallium or sestamibi SPECT for evaluation of suspected myocardial ischaemia,
      36 were selected according to the following criteria: previous non-Q wave
      myocardial infarction, normal QRS, negative T waves in two or more ECG leads and
      no significant ST segment depression or elevation at rest or during stress.
      Diagnosis of ischaemia relied upon the occurrence of reversible perfusion defects
      by scintigraphy and stress-induced wall motion abnormalities by echocardiography.
      During the test, T wave normalization (defined as a resting negative T wave
      becoming upright in one or more ECG leads during stress) occurred in 20 patients
      (group 1), while in 16 patients the T waves remained negative (group 2). The
      prevalence of ischaemia was higher in group 1 than in group 2 both by
      scintigraphy (85% vs 38%, P = 0.004) and by echocardiography (70% vs 32%, P =
      0.02). The sensitivity, specificity and accuracy of T wave normalization in the
      detection of ischaemia were 74%, 77% and 75% by SPECT and 74%, 65% and 69% by
      echocardiography respectively. CONCLUSION: In patients with non-Q wave myocardial
      infarction and suspected myocardial ischaemia, T wave normalization without
      concomitant ECG changes during dobutamine stress testing is associated with a
      higher prevalence of ischaemia compared to patients with persistent T wave
      inversion. This ECG finding should not be disregarded as a marker of ischaemia in
      that particular patient population.

PMID- 8733085
TI  - Short and long term effects of exercise training on the tonic autonomic
      modulation of heart rate variability after myocardial infarction.
AB  - We studied the effects of cardiac rehabilitation on the sympathovagal control of
      heart rate variability in 30 patients after a first, uncomplicated myocardial
      infarction. Twenty-two patients completed 8 weeks of endurance training
      (trained), while eight decided not to engage in the rehabilitation programme for
      logistical reasons, and were taken as untrained controls. Age, site of
      infarction, ejection fraction, ventricular diameter and stress test duration were
      similar in the two groups at baseline. Heart rate variability was evaluated 4
      weeks after infarction before starting rehabilitation, and repeated 8 weeks and
      one year later in both trained and untrained patients. Measures of heart rate
      variability, obtained from both time- and frequency-domain analysis of a 15 min
      ECG recording in resting conditions, were as follows: mean RR interval and its
      standard deviation (RRSD), the mean square successive differences (MSSD), the
      percent of RR intervals differing > 50 ms from the preceding RR (pNN50), the low
      and high frequency components of the autoregressive power spectrum of the RR
      intervals and their ratio (LF/HF). At baseline, heart rate variability was
      similar in trained and untrained patients. In the short term (8 weeks after
      infarction), training increased RRSD by 25% (P < 0.01), MSSD by 69% (P < 0.01),
      pNN50 by 120% (P < 0.01), and reduced LF/HF ratio by 30% (P < 0.01). The effects
      persisted after one year in trained patients. In untrained patients, the
      autonomic control of heart rate variability did not change 8 weeks after
      myocardial infarction and was only slightly modified by time. Thus, exercise
      training, performed for 8 weeks after a myocardial infarction, modifies the
      sympathovagal control of heart rate variability toward a persistent increase in
      parasympathetic tone, known to be associated with a better prognosis. This may
      partly account for the favourable outcome of patients who undergo rehabilitation.

PMID- 8733086
TI  - Aminophylline inhibits adaptation to ischaemia during angioplasty. Role of
      adenosine in ischaemic preconditioning.
AB  - The ability of brief periods of ischaemia to protect the heart from subsequent
      ischaemia has been termed "ischaemic preconditioning'. In order to assess the
      role of adenosine receptor stimulation in this phenomenon we studied the
      ischaemic preconditioning effect during angioplasty in 10 control patients and in
      10 patients pre-treated with 5 mg.kg-1 aminophylline, an adenosine receptor
      antagonist. The ischaemic response was assessed by analysis of the intracoronary
      electrocardiogram every 10 s during three consecutive inflations of 90 s with a
      reperfusion time of 180 s. The severity of transmural local ischaemia was
      expressed as the magnitude of the ST segment shift in relation to the time during
      each inflation. The control patients showed an improved tolerance to myocardial
      ischaemia: ST segment shift decreased from 1.42 +/- 0.49 mV at the end of the
      first inflation to 1.03 +/- 0.44 mV at the end of the third inflation (P <
      0.001). However, in patients pre-treated with aminophylline, the ischaemic
      response was not significantly different during three inflations. CONCLUSION:
      Aminophylline inhibits ischaemic preconditioning, as assessed by analysis of the
      intracoronary. ST segment changes during angioplasty. This suggests that
      ischaemic preconditioning is mediated by adenosine receptor stimulation in
      humans.

PMID- 8733087
TI  - Enterovirus persistence and myocardial damage detected by 111In-monoclonal
      antimyosin antibodies in patients with dilated cardiomyopathy.
AB  - BACKGROUND: Patients with dilated cardiomyopathy in whom enteroviruses in the
      myocardium are detected are more likely to die than those in whom no viruses have
      been demonstrated. The presence of enterovirus RNA in the myocardium at
      endomyocardial biopsy has been shown to be the strongest predictor of reduced
      survival. These results raise the question as to whether persistent virus might
      be responsible for continuing myocardial damage. Detection of myocardial cell
      damage is assessed using 111Indium-labelled monoclonal antimyosin antibodies. The
      present study was undertaken to address the question of whether the presence of
      myocardial cell damage by such antibodies in patients with dilated cardiomyopathy
      can be correlated with enterovirus persistence. PATIENTS AND METHODS: A series of
      19 consecutive patients diagnosed as having chronic dilated cardiomyopathy who
      were referred for evaluation for heart transplantation were studied with
      111Indium labelled monoclonal antimyosin antibodies. These patients and 10
      controls were screened for enterovirus RNA sequences in endomyocardial biopsy
      tissue by hybridization with an enterovirus group-specific cDNA probe. RESULTS:
      Antimyosin uptake, indicative of myocardial cell damage, was observed in 16 of 19
      patients (84%), with dilated cardiomyopathy, and enterovirus RNA sequences were
      detected in endomyocardial biopsies from four of these 16 patients (25%), but not
      in myocardium from the remaining three patients with a negative antimyosin scan,
      nor from any of 10 controls. CONCLUSIONS: Although these data do not establish a
      causal relationship between virus persistence in the myocardium and myocardial
      damage, the results obtained in the preliminary study support the hypothesis that
      enterovirus persistence is associated with continuing myocardial damage in
      patients with dilated cardiomyopathy.

PMID- 8733088
TI  - Clinical, adrenergic and heart endocrine measures in chronic atrial fibrillation
      as predictors of conversion and maintenance of sinus rhythm after direct current
      cardioversion.
AB  - The aim of this study was to evaluate clinical, adrenergic and endocrine factors
      that could predict sinus rhythm maintenance after direct current cardioversion in
      chronic atrial fibrillation. Nineteen patients with chronic non-rheumatic atrial
      fibrillation (mean duration 6 +/- 5 months) were studied. They were exercised 24
      h before cardioversion at maximum effort with the Naughton protocol. Heart rate
      and blood pressure at rest and exercise were recorded and blood samples were
      taken for the assessment of adrenergic activity, by measuring cyclic adenosine
      monophosphate, heart endocrine function, atrial natriuretic peptide and its
      second messenger, cyclic guanosine monophosphate. Fifteen of the 19 patients were
      initially converted to sinus rhythm (eight patients with external and seven
      patients with internal DC shocks). After 3 months eight patients remained in
      sinus rhythm and 11 had relapsed, most of them within the first month. On
      exercise the chronotropic response was lower in the group who remained in sinus
      rhythm than in the group in atrial fibrillation (peak heart rate 147 +/- 11
      beats.min-1 vs 165 +/- 24 beats.min-1 P = 0.02). During exercise, the systolic
      blood pressure in the sinus group reached higher values than in the group who
      relapsed (192 +/- 17 mmHg vs 176 +/- 18 mmHg, P = 0.03). Cyclic adenosine
      monophosphate increased significantly from rest to peak exercise in the sinus
      rhythm group (from 23 +/- 9 pmol.ml-1 to 31 +/- 15 mol.ml-1, P = 0.02) while it
      remained unchanged in the atrial fibrillation group (25 +/- 10 pmol.ml-1 to 24 +/
      8 pmol.ml-1, P = 0.02). For all 19 patients the difference in cyclic adenosine
      monophosphate between rest and exercise was negatively correlated with maximum
      heart rate (r = 0.58, P = 0.009). Atrial natriuretic peptide increased from rest
      to peak exercise in the sinus rhythm group (from 129 +/- 58 fmol.ml-1 to 140 +/-
      66 fmol.ml-1) while it remained unchanged in the group in which atrial
      fibrillation persisted or recurred (from 112 +/- 58 fmol.ml-1 to 111 +/- 53
      fmol.ml-1, P = 0.002). A significant correlation between atrial natriuretic
      peptide and cyclic guanosine monophosphate levels at exercise before
      cardioversion was found for the sinus rhythm group only (r = 0.76, P = 0.02). In
      patients with non-rheumatic chronic atrial fibrillation evaluation of clinical
      parameters such as heart rate and blood pressure changes during maximal exercise
      can be useful in the choice of suitable therapy. An inadequate increase in plasma
      cyclic-adenosine monophosphate and atrial natriuretic peptide on exercise could
      predict patients with more severe underlying disease, where cardioversion should
      not be recommended.

PMID- 8733089
TI  - Ventricular arrhythmias and athlete's heart. Role of signal-averaged
      electrocardiography.
AB  - The aim of this study was to assess the prevalence and the prognostic value of
      ventricular late potentials in apparently healthy top-level athletes with
      ventricular arrhythmias, and the effect of physiological myocardial hypertrophy
      (athlete's heart) on the electrogenesis of the signal-averaged electrocardiogram
      (ECG). Two groups of asymptomatic athletes without underlying heart disease were
      studied: group A consisted of 35 athletes without arrhythmias and group B of 25
      athletes with frequent and complex ventricular arrhythmias (ventricular ectopic
      beats > 5000.24 h-1 and ventricular couplets > 15.24 h-1). Late potentials were
      present if athletes had significantly prolonged filtered QRS and low amplitude
      signal duration and low root mean square voltages at both 25-250 Hz and 40-250 Hz
      filters. While late potentials were absent in all normal athletes of group A,
      they were present in seven of 25 (28%) athletes with arrhythmias of group B (P <
      0.003). Ten of 25 athletes (five with and five without late potentials) of group
      B underwent programmed ventricular stimulation using a protocol comprising up to
      three extrastimuli. No episode of sustained ventricular tachycardia was induced.
      In four of five athletes with late potentials and in one of five without them,
      unsustained ventricular responses were induced. Echocardiographically determined
      left ventricular mass found in both groups of athletes did not influence the
      pathological result of the signal-averaged ECG parameters. This study shows the
      applicability of the signal-averaged ECG in identifying ventricular late
      potentials in a selected population of top-level athletes with frequent and
      complex ventricular arrhythmias and without overt heart disease; it also shows
      that the presence of late potentials is not influenced by left ventricular mass,
      even if extreme ( > 350 g), and it is correlated to a non-sustained ventricular
      response during an electrophysiological study.

PMID- 8733090
TI  - Continuation of antiarrhythmic drugs, or arrhythmia surgery after multiple drug
      failures. A randomized trial in the treatment of postinfarction ventricular
      tachycardia.
AB  - BACKGROUND: In patients with postinfarction sustained ventricular tachycardia
      showing one or more antiarrhythmic drug failures, the question is how long to
      proceed with new drug trials before deciding to perform map-guided arrhythmia
      surgery. Although the techniques of this surgery developed rapidly in the early
      1980s, this therapy may be offset by damage to residual left ventricular
      function. However, surgery has been shown to be very effective in selected groups
      of patients. METHODS: A randomized study was carried out in patients with
      postinfarction ventricular tachycardia and eligible for arrhythmia surgery based
      on residual left ventricular function. Therapy failure was defined by the
      occurrence of the following events: spontaneous recurrence of ventricular
      tachycardia or ventricular fibrillation, sudden cardiac death, inducibility of
      sustained ventricular tachycardia or ventricular fibrillation with programmed
      stimulation of the heart, symptomatic non-sustained ventricular tachycardia
      requiring therapy or side-effects of antiarrhythmic drugs requiring withdrawal.
      In the drug limb, failure of the first antiarrhythmic drug was accepted but
      failure of a second and different drug was regarded as true therapy failure.
      RESULTS: After randomization, antiarrhythmic drug therapy was administered in 33
      patients, and 30 patients underwent surgery. Neither group differed in baseline
      characteristics, and the mean number of drug failures before randomization was
      2.7. The Kaplan-Meier therapeutic failure of antiarrhythmic drugs was 39 +/- 11%,
      42 +/- 11% and 51 +/- 18% at 0.5-, 1- and 4-year follow-up, respectively, whereas
      the therapeutic failure of cardiac surgery was 37 +/- 11%, 37 +/- 11% and 50 +/-
      20% at 0.5, 1 and 4 years, respectively, showing no statistical difference. The 1
      and 4-year Kaplan-Meier survival of the antiarrhythmic drug-treated group was 91
      +/- 6% and 78 +/- 15%, respectively, and of the surgical group 92 +/- 6% and 59
      +/- 20%, respectively, and did not differ between either group. However, the
      relative risk for total cardiac death was higher in the surgical limb than in the
      drug limb (relative risk 2.2, CI 0.68-7.48). CONCLUSION: This study demonstrated
      no difference between the therapeutic result of continuation of two different
      antiarrhythmic drugs and that of arrhythmia surgery. Despite the small number of
      patients studied, it is recommended that drug therapy should continue as long as
      this regimen is tolerated by the patient. When true drug refractoriness or side
      effects of drugs arise, arrhythmia surgery offers a valuable alternative.
      However, when additional reasons for cardiac surgery exist, arrhythmia surgery
      should be undertaken earlier and may become the first choice of treatment of
      postinfarction ventricular tachycardia.

PMID- 8733091
TI  - Cost benefit analysis of single and dual chamber pacing for sick sinus syndrome
      and atrioventricular block. An economic sensitivity analysis of the literature.
AB  - The benefits of dual (DDD) over single chamber pacing (VVI) have been
      demonstrated in haemodynamics, exercise capacity, quality of life and reduced
      complications in atrioventricular block and sick sinus syndrome. The literature
      was reviewed to provide complication rates for dual and VVI pacing. Cost
      calculations were based on United Kingdom 1991 prices. Over a 10-year period, a
      computer model calculated the incidence and prevalence of atrial fibrillation,
      stroke, permanent disability, heart failure and mortality in six patient
      categories: sick sinus syndrome paced VVI, sick sinus syndrome upgraded to DDD,
      sick sinus syndrome paced DDD from outset, atrioventricular block paced VVI and
      those upgraded to DDD and atrioventricular block paced initially DDD.
      Calculations were based on intention to treat. The 10 year survival with DDD vs
      VVI pacing was 71% vs 57% in sick sinus syndrome and 61% vs 51%, respectively, in
      atrioventricular block. In both indications the prevalence of heart failure in
      the 10 year survivors was 60% lower with DDD pacing. In sick sinus syndrome
      patients paced VVI, 36% had severe disability while only 8% experienced this with
      DDD pacing. For atrioventricular block the figures were, respectively, 22% vs 3%.
      The difference in 10 year cumulative cost between VVI and DDD is 13 times the
      purchase price of a VVI pulse generator for sick sinus syndrome and 7 times for
      atrioventricular block. In the third year after implantation the cumulative costs
      of DDD were lower than for VVI for both indications. Dual chamber pacing for both
      indications, sick sinus syndrome and atrioventricular block, is both clinically
      and cost effective.

PMID- 8733092
TI  - Quality of life in octogenarians after valve replacement due to aortic stenosis.
      A prospective comparison with younger patients.
AB  - BACKGROUND: Results of aortic valve surgery in octogenarians have been evaluated
      as event-free survival. However, little attention has been given to quality of
      life aspects. METHODS: Thirty-two consecutive patients, mean age 83 +/- 2 years,
      undergoing valve replacement due to aortic stenosis, were compared to 30
      patients, mean age 71 +/- 3 years, undergoing the same procedure. Mortality,
      morbidity and quality of life were studied. An interview was performed before
      surgery and 3 and 12 months postoperatively. The questionnaire contained items
      related to self-rated health, symptoms, physical ability, sleep disturbances and
      social and emotional functioning. RESULTS: Pre-operatively the older patient
      group was in a worse condition with a higher NYHA functional class and a more
      pronounced cardiomegaly. They had more cardiac symptoms and were more depressed.
      The control group had a higher score for physical ability and rated their quality
      of life as better. Postoperatively there was a higher early mortality rate in the
      octogenarians (9% vs 0%; ns). After 3 months, improvement of functional status
      and relief of symptoms was observed in both groups. Physical ability improved and
      the depression score decreased significantly in both groups. Self-rated health
      and quality of life improved. One year after valve replacement the improvement in
      quality of life was of a similar magnitude in the two groups. CONCLUSION:
      Following aortic valve replacement, octogenarians, despite a more compromised pre
      operative status showed an improvement in symptomatology, physical ability and
      general well being, of a similar magnitude to that of the younger patients group.
      These findings lend further support to the recommendation that valve replacement
      should be performed in octogenarians with symptomatic aortic stenosis.

PMID- 8733093
TI  - Potential cardioembolic sources of stroke in patients less than 60 years of age.
AB  - Minor potential cardioembolic sources of stroke such as atrial septal aneurysm or
      patent foramen ovale are important risk factors for cryptogenic stroke. We aimed
      to determine the prevalence of these abnormalities through an exhaustive
      aetiological work-up. One hundred and eighteen stroke patients under 60 years of
      age, who had no evidence of a significant cardiac source of embolism, were
      classified into four groups following transoesophageal echocardiography and
      assessment of cervical arteries. Group A comprised 30 patients (25.4%) who had an
      arteriopathy, probably related to stroke without any cardiac abnormality; group
      B, had only a potential cardiac source; group C, nine (7.6%) had an obvious
      arterial source of stroke and incidental cardiac abnormalities; group D, 30
      (25.4%) had neither cardiac or arterial source. Data were analysed with the Chi
      square test to compare risk factors between groups, and variance analysis was
      used to compare age between groups. Significance was assessed as P < 0.05.
      Fisher's exact test was used to test the association between arterial septal
      aneurysm and patient foramen ovale. In groups B and D atrial septal aneurysm
      represented 56.8% of the cardiac abnormalities and was diagnosed in 35.4% of the
      79 patients who had an unexplained stroke, and a patent foramen ovale was found
      in 34.1% of the patients. According to Fisher's exact test, atrial septal
      aneurysm was significantly associated with patent foramen ovale (P < < 0.001). On
      this basis, one fourth of the patients might be said to have had a truly
      cryptogenic stroke as the aetiological work-up failed to demonstrate any source
      of stroke. Comparison between groups showed that in 23% of the patients in whom
      an arterial source was detected, there was also a potential cardioembolic source
      (group C), vs 62% in patients who had no arterial source (groups B and D) (P =
      0.0007). Our study confirmed the strong association between atrial septal
      aneurysm, patent foramen ovale and stroke. Although there was a lower incidence
      of cardiac risk factors for stroke in patients who had cervical artery disease,
      we suggest that all patients who have a stroke without evidence of a major
      cardiac source should undergo transoesophageal echocardiography, in order to
      ensure a better prevention.

PMID- 8733094
TI  - Exercise tolerance in patients with mitral stenosis before and after acute
      percutaneous mitral valvuloplasty. Role of lung diffusing capacity limitation?
AB  - The aim of this study was to specify in patients with tight mitral stenosis
      whether lung diffusing capacity could play a role in their exercise intolerance.
      A similar study was recently carried out in patients with moderate chronic heart
      failure. Ten patients with tight mitral stenosis were studied before and 6 months
      after successful percutaneous transvenous balloon valvuloplasty and compared to
      six control subjects. Measurements of diffusing capacity, evaluated by the lung
      transfer factor (TLCO) and by the transfer coefficient (TLCO/VA), obtained at
      rest and during early recovery after cardiopulmonary exercise testing were
      performed. Cardiac output was determined non-invasively, both at rest and during
      exercise, using the carbon dioxide exponential rebreathing technique. Prior to
      valvuloplasty, TLCO and TLCO/VA were not different at rest between the two
      groups. During exercise, patients differed from control subjects, with lower
      oxygen uptake (P < 0.001) and lower cardiac output at peak exercise (P < 0.001).
      These values at peak exercise were significantly correlated (P = 0.02; r = 0.75).
      Moreover, patients differed from control subjects at early recovery after peak
      exercise with an absence of increase in TLCO (P < 0.05). Six months after
      valvuloplasty, a decrease of both TLCO (P < 0.01) and TLCO/VA (P < 0.05) was
      observed at rest. During exercise, comparison of patients demonstrated a
      significant increase of both peak exercise oxygen uptake (SLVO2, P < 0.01) and
      cardiac output (P < 0.001). At early recovery after peak exercise there was a
      significant increase in TLCO (P < 0.05) and TLCO/VA (P < 0.01), such that a delta
      TLCO and a delta TLCO/VA appeared (P < 0.05) identical to that observed in
      control subjects. Moreover, delta SLVO2 was significantly correlated in patients
      with delta Q+ delta TLCO/VA (P = 0.02; r = 0.72). In conclusion, this study
      suggests a role, at least partial, of lung diffusing capacity in exercise
      intolerance in patients with tight mitral stenosis and in the improvement of
      their aerobic exercise capacity demonstrated after successful percutaneous
      balloon valvuloplasty.

PMID- 8733095
TI  - Cardiovascular responses to an acute volume load in deep hypothermia.
AB  - Intravenous administration of warm fluids is used clinically as first aid either
      alone or as a contributing method, to rewarm hypothermic patients back to normal
      body temperature. The aim of this study was to determine the effects of an acute
      volume load in hypothermic conditions on the canine circulatory system. Cardiac
      catheterization was performed on 18 anaesthetized beagle dogs. Eleven of them
      were cooled and at a body temperature of 25 degrees C they received 40 ml.kg-1
      dextran administered intravenously. The control group received dextran at normal
      body temperature. During cooling the body from 37 degrees C down to 25 degrees C
      most of the volume load escaped from the circulation due to extravazation. During
      rewarming, the opposite effect could be seen and the volume load persisted up to
      29 degrees C and signs of cardiac decompensation were observed. According to
      these results, the intravenous administration of warm fluids to rewarm
      hypothermic patients should not be used routinely when hypovolaemia is the only
      result of hypothermia.

PMID- 8733096
TI  - Factors of importance to Doppler indices of left ventricular filling in 50-year
      old healthy subjects.
AB  - Age is an important determinant of Doppler indices of left ventricular diastolic
      filling in normal subjects. To define reference values and factors of importance
      to Doppler indices of left ventricular filling in subjects of similar age, 58 men
      and 76 women aged 50 years underwent Doppler echocardiography. All those taking
      part in the study were healthy. When gender was analysed in a multivariate model
      it showed a significant independent correlation with the peak velocity of early
      diastolic filling (E wave) (P < 0.001) and the early to atrial peak velocity
      (E/A) ratio (P < 0.01). The peak E wave velocity was 0.75 +/- 0.11 m.s-1 vs 0.66
      +/- 0.10 m.s-1 (P < 0.001) and the E/A ratio was 1.24 +/- 0.25 vs 1.14 +/- 0.20
      (P < 0.05) in women and men, respectively. In multivariate analyses, heart rate,
      diastolic blood pressure and body mass index correlated independently with the
      E/A ratio in women (P < 0.001 for all), whereas in men, heart rate, diastolic
      blood pressure, body mass index and left ventricular diameter correlated
      independently with the E/A ratio (P < 0.001 for all). Doppler measurements of
      left ventricular filling in 50-year-old healthy subjects showed a wide variation
      and were significantly associated with heart rate, diastolic blood pressure, body
      mass index and gender.

PMID- 8733097
TI  - Three-dimensional echocardiography using a transoesophageal imaging probe.
      Potentials and technical considerations.
AB  - Appreciation of three-dimensional relationships could be useful in cardiac
      diagnosis, decision making and planning of surgery. However, current ultrasound
      techniques provide only two-dimensional views. A recently developed
      echocardiographic computerized tomography unit allows reconstruction of three
      dimensional images from a series of transoesophageal slices. To evaluate the
      potentials and limitations of this technique we performed echo computer
      tomographic examinations in 104 patients with a total number of 227 scans. All
      but two patients tolerated the procedure well and no serious complications were
      encountered. Indications for echo computer tomography included coronary artery
      disease, valvular heart disease, atrial masses, myocardial infarction, mitral and
      aortic valve replacement, aortic aneurysm and congenital defects. Most of the
      anatomical structures could be visualized with the best results obtained for the
      left atrium, the left ventricular outflow tract and the aortic and mitral valve
      apparatus. However, a variety of technical factors must be considered to achieve
      optimal results and to avoid misinterpretation. In 86% of patients the underlying
      pathology could be visualised by echo-computed tomography, particularly
      congenital defects such as those of the atrial or ventricular septa, but mitral
      valve pathologies provided the best results. In these cases three-dimensional
      imaging led to a better perception and understanding of structural relationships.
      In conclusion, despite current limitations in data acquisition, processing and
      computing power, echo computer tomography has the potential to provide relevant
      information in selected clinical settings.

PMID- 8733098
TI  - Infra-low dose dipyridamole test. A novel dose regimen for selective assessment
      of myocardial viability by vasodilator stress echocardiography.
AB  - Low (0.56 mg.kg-1 over 4 min) and high (0.84 mg.kg-1 over 10 min) doses of
      dipyridamole can identify viable myocardium through the contractile recovery of
      basally dyssynergic regions; however, it also induces ischaemia in susceptible
      patients. The aim of this study was to assess the potential of an "infra-low'
      dose of dipyridamole to selectively identify myocardial viability, independently
      evaluated by low dose dobutamine. Forty patients with resting dyssynergy and
      angiographically assessed coronary artery disease (1-vessel in 18, 2-vessel in
      12, and 3-vessel in 10 patients) separately underwent a low dose dobutamine (5-10
      micrograms.kg-1.min-1 for 3 min) echo test and an infralow dose (0.28 mg.kg-1
      over 4 min) dipyridamole echo test. Systolic blood pressure (rest: 131 +/- 19
      mmHg) changed slightly after dobutamine (137 +/- 21, P < 0.05 vs rest) and
      remained stable after dipyridamole (130 +/- 17, P = ns vs rest). Heart rate
      (rest: 68 +/- 13 beats.min-1) was also unchanged after dipyridamole (69 +/- 12, P
      = ns vs rest) and increased slightly after dobutamine (71 +/- 15, P < 0.05 vs
      rest and vs dipyridamole). No patient developed echocardiographic or
      electrocardiographic signs of ischaemia after either dipyridamole or dobutamine.
      Of the 243 segments with baseline dyssynergy, 70 were responders (i.e. they
      showed an improvement of 1 grade or more, from 1 = normal/hyperkinetic to 4 =
      dyskinetic in a 16-segment model of the left ventricle) by both dipyridamole and
      dobutamine, 157 were non-responders (i.e. they showed no change) by both
      dipyridamole and dobutamine, and 16 showed discordant results (five responders by
      dipyridamole only; 11 by dobutamine only). The overall concordance of
      dipyridamole and dobutamine was 93%. An echocardiographic follow-up could be
      obtained > 6 weeks after successful revascularization (achieved with angioplasty
      in 17, with by pass surgery in 3) in 19 patients and showed an improvement of one
      grade or more in 50 segments (viable) and no improvement in 50 segments
      (necrotic). The sensitivity of dobutamine and dipyridamole for predicting
      recovery was 76 and 78% respectively (P = ns); the specificity of both tests was
      94%. In conclusion, infra-low dose dipyridamole is a haemodynamically neutral
      stress test which does not affect either heart rate or systolic blood pressure;
      it allows myocardial viability to be explored selectively, without eliciting
      ischaemia; it shows excellent overall concordance with low dose dobutamine and
      has good sensitivity and excellent specificity for predicting functional recovery
      following successful revascularization.

PMID- 8733099
TI  - Tomographic myocardial imaging with technetium-99m tetrofosmin. Comparison with
      tetrofosmin and thallium planar imaging and with angiography.
AB  - Technetium-99m tetrofosmin is a new myocardial imaging agent with improved
      handling and kinetic characteristics. The purpose of this study was to compare
      the ability of planar and SPECT Tc-99m tetrofosmin imaging with Thallium-201
      planar data to detect coronary artery disease and individual vessel lesions ( >
      50% diameter stenosis). Seventy-two patients with definite or suspected coronary
      artery disease were included. Sixty-three had angiographic evidence of coronary
      artery disease, among whom 42 had had a previous myocardial infarction, while 21
      had not. The total number of diseased arteries was 111. Patients underwent
      symptom-limited treadmill or bicycle exercise to similar endpoints. Thallium and
      tetrofosmin images were analysed separately by consensus reading. Interpretation
      was made for five standard anatomical regions (anterior, septal, inferior,
      lateral and apex), classified into four categories (normal, reversible, fixed and
      mixed defects). Sensitivity and specificity to detect coronary artery disease
      were 71% and 78% for Thallium-201 vs 68% and 78% for tetrofosmin by planar
      imaging, and 87% and 89% for tetrofosmin by SPECT. The improved sensitivity of
      SPECT was confirmed both in patients with and without previous myocardial
      infarction. The sensitivity to detect individual vessel lesions was improved by
      SPECT (59% tetrofosmin SPECT vs 50% thallium planar and 51% tetrofosmin planar).
      Individual vessel lesion detection by SPECT was 50% for the left anterior
      descending coronary artery, 42% for the left circumflex and 86% for the right
      coronary artery. This study confirms the value of technetium-99m tetrofosmin as a
      myocardial imaging agent. Improvements in diagnosis and in evaluating extent of
      disease can be expected from using SPECT.

PMID- 8733100
TI  - Nodal re-entry tachycardia with angina treated with adenosine.

PMID- 8733101
TI  - Rare cause of pure aortic regurgitation: congenital quadricuspid aortic valve.

PMID- 8733102
TI  - And now for vertical equity? Some concerns arising from aboriginal health in
      Australia.

PMID- 8733103
TI  - Individual cigarette consumption and addiction: a flexible limited dependent
      variable approach.
AB  - A variety of limited dependent variable models have been used in microeconometric
      studies of smoking. We present a general model of the simultaneous decisions of
      how much to smoke and whether to quit, which allows a more flexible
      parameterization and distributional assumptions. The model incorporates the fixed
      costs associated with quitting and allows for the separate influence of addiction
      on participation and consumption. The model is applied to data on smoking from
      the 1984-85 UK Health and Lifestyle Survey, and is shown to outperform a range of
      nested models that have been used extensively in the empirical literature.

PMID- 8733104
TI  - Subsidized dental care for young men: its impact on utilization and dental
      health.
AB  - An important part of Norwegian welfare policy is provision of free dental care
      for children up to the age of 18. After that age some counties have introduced a
      public subsidy scheme for young people aged 19-20 years, where 75% of their
      dental care expenses are covered. After the age of 21, all patients have to pay
      the costs for dental care themselves. The focus of the present work was to
      examine the effect that the public subsidy scheme for young adults had on demand
      for dental care, and its effect on dental health. The analyses were performed on
      2 extensive sets of survey data. The major finding was that the public subsidy
      scheme had no effect on demand for dental care. In addition, there was no
      relationship between whether these young adults were covered by the subsidy
      scheme and dental health.

PMID- 8733105
TI  - Selection bias in GP fundholding.
AB  - This paper uses a logistic regression model based on 1993 data for general
      practices in a single Family Health Services Authority (Lincolnshire) to analyse
      the differences in characteristics between existing fundholding (up to and
      including wave three) and non-fundholding practices. A high degree of
      classification accuracy is obtained. Fundholders are revealed to be more likely
      than non-fundholders to meet a number of the various quality criteria laid down
      by central government following the 1990 National Health Services Act, for
      example, with respect to prescribing cost control, minor surgery and cervical
      screening uptake. The model is employed to forecast the fourth wave of
      fundholding and poor predictions suggest the existence of a structural break in
      the characteristics of fundholders between those in the first three waves and
      those of wave four. The evidence presented also supports the existence of
      selection bias in the first three waves of fundholding, although further logistic
      regression analysis reveals a form of such bias in the fourth wave also.

PMID- 8733106
TI  - The time trade-off method: results from a general population study.
AB  - An important consideration when establishing priorities in health care is the
      likely effects that alternative allocations of resources will have on health
      related quality-of-life (HRQoL). This paper reports on a large-scale national
      study that elicited the relative valuations attached by the general public to
      different states of health (defined in HRQoL terms). Health state valuations were
      derived using the time trade-off (TTO) method. The data from 3395 respondents
      were highly consistent, suggesting that it is feasible to use the TTO method to
      elicit valuations from the general public. The paper shows that valuations for
      severe health states appear to be affected by the age and the sex of the
      respondent; those aged 18-59 have higher valuations than those aged 60 or over
      and men have higher valuations than women. These results contradict those
      reported elsewhere and suggest that the small samples used in other studies may
      be concealing real differences that exist between population sub-groups. This has
      important implications for public policy decisions.

PMID- 8733107
TI  - An exercise on the feasibility of carrying out secondary economic analyses.
AB  - Purchasers of health services need up to date information on cost-effectiveness
      of interventions to help in prioritising spending. But economists have not yet
      developed a formal methodology for reviewing and summing up evidence from
      individual economic evaluations which may have been conducted at different times
      and in different places, or indeed for assessing whether such systematic reviews
      are possible in this context. This paper discusses the problems of reviewing
      available economic information, using a body of literature on the economics of
      influenza vaccination to illustrate some relevant issues. First, the paper
      examines alternative methods for adjusting prices to take into account
      differences in currency and time periods: Retail Price Indices are compared with
      health specific inflation indices, and exchange rates are compared with
      Purchasing Power Parity (PPP) data. For the studies reviewed, the choice of
      conversion method made little practical difference. Secondly, the paper explores
      the possibility of summarising the results of a review in terms of quantities of
      resources used, rather than prices. This method is constrained by the available
      data, but could be more generally useful as it allows direct comparison of
      underlying technologies, and calculation of costs by attaching local unit costs
      to the resources associated with an intervention. These two exercises highlight
      many of the problems that arise in generalising from economic studies. Both
      methods need to be developed further if they are to be useful to decision makers.

PMID- 8733108
TI  - Costing neonatal care alongside the ECMO trial.

PMID- 8733109
TI  - Age-related change of phosphatidylcholine hydroperoxide and
      phosphatidylethanolamine hydroperoxide levels in normal human red blood cells.
AB  - The age-related occurrence of phosphatidylcholine hydroperoxide (PCOOH) and
      phosphatidylethanolamine hydroperoxide (PEOOH) in normal human red blood cells
      (RBC) was confirmed by using chemiluminescence detection-high performances liquid
      chromatography (CL-HPLC). The concentration (mean +/- S.D.) for the healthy young
      adult (22-27 of age, n = 20) was 93 +/- 17 pmol PCOOH and 121 +/- 20 pmol
      PEOOH/ml packed RBC, while for the aged adult (56-92 of age, n = 20) the peroxide
      content was significantly higher, 162 +/- 52 pmol PCOOH and 186 +/- 40 pmol
      PEOOH/ml packed RBC. These results indicate that oxidative stress occurs
      constantly on RBC, even in normal humans, and that the susceptivity significantly
      increases with age.

PMID- 8733110
TI  - Effects of cellular aging on the induction of c-fos by antioxidant treatments.
AB  - The proto-oncogene c-fos (the cellular homolog of v-fos, Finkel-Biskis-Jenkins
      (FBJ) murine osteogenic sarcoma virus) encodes a major component of the activator
      protein-1 (AP-1) transcription factor. Serum stimulation as well as oxidizing
      treatments induce transitory increases in c-fos mRNA abundance. The induction of
      c-fos by serum stimulation is also known to decline during proliferative
      senesence. In this study, we examined the effects of two classes of antioxidants
      on the induction of c-fos in early and late passage human fetal lung fibroblasts
      (WI-38). N-acetyl cysteine (NAC) induces c-fos transcription in both early and
      late passage cells, while nordihydroguaiaretic acid (NGA) induced c-fos
      transcription in early passage cells but fails to stimulate it in late passage
      cells. Since we had previously observed an age-related decline in protein kinase
      C (PKC) translocation from the cytosol to the membrane, following its activation,
      and because PKC activation appears to be involved in the NGA induction of c-fos
      we examined the relative protein abundances of several PKC isoforms in early and
      late passage cells. Additionally, we examined the protein abundance of several
      members of the MAP kinase pathway which could play a role in c-fos induction by
      the PKC-dependent pathway. We were unable to detect PKC-beta or theta in early or
      late passage cells. Late passage cells contained a slightly greater abundance of
      PKC alpha, gamma and epsilon than cells at an early passage. No other differences
      in PKC isoforms or in members of the MAP kinase family were observed in early or
      late passage cells. These results clearly demonstrate that at least some pathways
      leading to c-fos induction remain intact in late passage cells. While we were
      unable to detect any decreases in PKC isoforms or MAP kinase proteins we cannot
      exclude the possibility that functional decrements accumulate in these proteins
      during senesence.

PMID- 8733111
TI  - Alteration of 6-phosphofructo-1-kinase subunit protein, synthesis rates, and mRNA
      during rat neonatal development.
AB  - For the three 6-phosphofructo-1-kinase (PFK) subunits in heart, skeletal muscle,
      liver and kidney, developmentally-associated changes in protein, mRNA and
      apparent synthesis rates were observed. During neonatal maturation, all three
      phenomena for the M-type in heart and skeletal muscle exhibited large increases.
      Also, during neonatal development, the L-type and C-type subunits were unaffected
      in heart but disappeared from skeletal muscle. In the newborn liver and kidney,
      the amounts of each type of PFK subunit protein were nearly identical. During
      neonatal development, the levels of all three PFK subunit proteins in kidney
      increased more than twofold; and this was associated with a similar increase in
      apparent subunit synthesis rates and mRNA levels. During liver neonatal
      development, the L-type subunit protein, synthesis and mRNA levels also increased
      more than twofold. However, during hepatic maturation, M-type subunit protein,
      synthesis and mRNA levels were unchanged and apparently unaffected. The C-type
      subunit protein during neonatal liver development decreased approximately 80% as
      did its apparent synthesis rate. These data suggest that regulation of the
      alteration of the PFK subunit proteins during neonatal maturation can vary among
      these tissues and is not the same for each subunit type. Different mechanisms,
      such as transcription, translation, and mRNA stability could be involved.

PMID- 8733112
TI  - CD45 isoforms expression on CD4+ and CD8+ T cells throughout life, from newborns
      to centenarians: implications for T cell memory.
AB  - CD4+ and CD8+ peripheral blood T lymphocytes show mutually exclusive expression
      of CD45RA or CD45R0, two isoforms of the common leukocyte antigen that seem to
      recognize so-called virgin/unprimed and memory/activated T cells. The expression
      of these isoforms has been studied by three colour cytofluorimetric analysis on
      CD4+ or CD8+ peripheral blood CD3+ cells from 22 healthy centenarians, analyzed
      in a context of 202 healthy donors 0-110 years old. An age-related unbalance of
      virgin and memory cells was found between CD4+ and CD8+ subsets. As expected, at
      birgh 95-99% of the CD3+ lymphocytes expressed the CD45RA isoform. A rapid
      increase of CD45R0+ cells was observed in the first 2-3 decades of life, this
      phenomenon being much more pronounced on CD4+ cells. Subsequently, the increase
      of the 'memory' compartment was much less rapid, so that in centenarians a
      consistent reservoire of CD45RA+ among CD4+ cells was still present (about 20%).
      In these exceptional individuals the percentage of CD45RA+ cells among CD8+ T
      lymphocytes was even higher (about 50%), and only slightly lower than that of
      young donors (about 55-60%). Thus, the main changes occurred at a different rate
      in CD4+ (about 20%). In these exceptional individuals the percentage of CD45RA+
      cells among CD8+ T lymphocytes was even higher (about 50%), and only slightly
      lower than that of young donors (about 55-60%). Thus, the main changes occurred
      at a different rate in CD4+ and in CD8+ T cells, at an age of between 0 and 30
      years, when the thymus is still functionally active. Interestingly, no difference
      in the usage of CD45 isoforms was observed within T cells bearing four different
      V beta-T cell receptor (TCR). The significance of this age-related unbalance is
      unknown. However, the presence of a great number of CD45RA+ T lymphocytes within
      the CD4+ and the CD8+ T cell subsets even in the peripheral blood of centenarians
      poses the problem of their origin (thymus? extrathymic sites?), of their
      functional role and of their lifespan. Moreover, the data on centenarians suggest
      that they may represent a very selected population where a slowing of
      immunosenescence occurs.

PMID- 8733113
TI  - Defects of the respiratory chain in various tissues of old monkeys: a
      cytochemical-immunocytochemical study.
AB  - The aim of the present study was to evaluate if defects of the respiratory chain
      known to occur in humans, also exist in lower primates. Cytochemical
      immunocytochemical studies of the respiratory chain enzymes in five monkeys (10
      25 years of age) showed defects of ubiquinone cytochrome-c-oxidoreductase
      (complex III), of cytochrome-c-oxidase (complex IV) and of ATP-synthase (complex
      V) in the limb muscles, diaphragm, heart muscle and extraocular muscles of three
      old animals (about 25 years) and also in the heart muscle of two younger animals
      (10 and 15 years). Characteristically, the defects were randomly distributed and
      there was no loss of succinate-dehydrogenase (complex II) in the fibres.
      Ultracytochemistry-immunocytochemistry of complex IV disclosed that in an
      involved fibre segment all the mitochondria exhibited the defect. The highest
      number of defects was observed in the extraocular muscle (up to 340/cm2) while
      the lowest defect density was present in the limb muscles (2-5/cm2). Defects of
      complex IV occurred two to three times more often than defects of complex III and
      besides isolated defects of complex III and IV, combined defects of both
      complexes were also observed. Defects of complex V occurred exclusively in
      combination and were rarely seen. Using subunit specific antisera against complex
      IV, it could be demonstrated at light and electron microscopic level that loss of
      activity of cytochrome-c-oxidase was associated with a loss both of
      mitochondrially and nuclearly coded subunits of the enzyme. In summary, aging in
      lower primates and humans is characterised by a highly similar defect expression
      of the respiratory chain enzymes, with intercellular and interorgan differences
      of the aging process, underlining the universal nature of the involved
      pathogenetic mechanisms.

PMID- 8733114
TI  - An analysis of the food plants and drug plants of native North America.
AB  - This paper compares the medicinal and food floras of the native peoples of North
      America. There is a surprising overlap of these floras by both family and taxon.
      Yet there are also substantial differences-food and medicine tend to involve
      different plant parts, plant habit, and plant character. The similarities and
      differences are considered in an evolutionary context and a theoretical
      perspective is suggested to account for these facts.

PMID- 8733115
TI  - Effects of the volatile oil of Nigella sativa seeds on the uterine smooth muscle
      of rat and guinea pig.
AB  - The effects of the volatile oil of Nigella sativa seeds on the uterine smooth
      muscle of rats and guinea pigs was tested in vitro using isolated uterine horns.
      The volatile oil of Nigella sativa seeds inhibited the spontaneous movements of
      rat and guinea pig uterine smooth muscle and also the contractions induced by
      oxytocin stimulation. These effects were concentration-dependent and reversible
      by tissue washing. These data suggest that this volatile oil may have some anti
      oxytocic potential.

PMID- 8733116
TI  - Preliminary antimicrobial screening of four South African Asteraceae species.
AB  - Organic and aqueous solvent extracts of Arctotis auriculata Jacq., Eriocephalus
      africanus L., Felicia erigeroides DC., and Helichrysum crispum (L.) D. Don, were
      investigated for selective antimicrobial activities. Organic extracts of A.
      auriculata and H. crispum inhibited the growth of Mycobacterium smegmatis. The
      same extracts, together with organic extracts of F. erigeroides, were active
      against Pseudomonas aeruginosa. Antifungal activities against Candida albicans
      were exhibited by organic extracts of E. africanus, F. erigeroides, and H.
      crispum. Organic extracts of A. auriculata and E. africanus, as well as the
      aqueous extract of the latter plant, were active against Staphyllococcus aureus.

PMID- 8733117
TI  - Molluscicidal activity of neem (Azadirachta indica A. Juss).
AB  - Molluscicidal property of Azadirachta indica A. Juss (neem) against the snails
      Lymnaea acuminata and Indoplanorbis exustus was studied. It was observed that the
      molluscicidal activity of the leaf, bark, cake, neem oil and the neem-based
      pesticides, achook and nimbecidine, was both time- and dose-dependent. The toxic
      effect of pure azadirachtin against both the snails was greater than the
      synthetic molluscicides.

PMID- 8733118
TI  - Inhibition of herpes simplex virus type 1 by aqueous extracts from shoots of
      Helichrysum aureonitens (Asteraceae).
AB  - Helichrysum aureonitens, a southern African medicinal plant reported to have
      antibacterial properties, was evaluated for antiviral activity against herpes
      simplex virus type 1 (HSV-1) in vitro. The crude aqueous extract from shoots of
      H. aureonitens at a concentration of 1.35 mg/ml (w/v) showed significant
      antiviral activity on HSV-1 in human lung fibroblasts as demonstrated by the
      absence of a cytopathic effect.

PMID- 8733119
TI  - Ritual and medicinal plants of the Ese'ejas of the Amazonian rainforest (Madre de
      Dios, Peru).
AB  - The Ese'eja is a hunter-fisher-gatherer tribe of Amerindians which occupies the
      south-eastern part of Peru. Their culture cannot be disassociated from religious
      beliefs. Disease can be caused by accident, distraction or indolence, or by evil
      powers. These evil powers come either from the direct action of a harmful shaman
      or by interactions with the Devil. A description of shamanic practices is given
      to elucidate the position of health practices in Ese'eja culture, which includes
      the use of medicinal and ritual plants. Aspects of ayahuasca (Banisteriopsis
      caapi (Spruce) Morton, Malpighiaceae) ritual in shaman initiation and in healing
      rituals are presented. Diagnosis and treatment include invocation to the
      ayahuasca spirit. Plants used as medicine or invoked for healing are presented.

PMID- 8733120
TI  - In vitro cytotoxicity and immunomodulating property of Rhaphidophora korthalsii.
AB  - An in vitro cytotoxic screening of extracts of Rhaphidophora korthalsii indicated
      cytotoxicity in the ether fraction. ED50 values of the extract against P388, Molt
      4, KB and SW 620 were 12, 14, 8 and 13 micrograms/ml, respectively. The extract
      was relatively more toxic on P388 and Molt 4 cell lines at concentrations of 50
      micrograms/ml and 100 micrograms/ml. Screening with mouse splenocytes showed that
      the hot water extract had splenocytes stimulating activity.

PMID- 8733121
TI  - Construction of a mouse model of Charcot-Marie-Tooth disease type 1A by
      pronuclear injection of human YAC DNA.
AB  - Construction of animal models of human inherited diseases is particularly
      important for testing gene therapy approaches. Towards this end, we constructed a
      mouse model for Charcot-Marie-Tooth disease type 1A by pronuclear injection of a
      YAC containing the human PMP22 gene. In one transgenic line, the YAC DNA is
      integrated in about eight copies and the PMP22 gene is strongly expressed to give
      a peripheral neuropathy closely resembling the human pathology. The disorder is
      dominant, causes progressive weakness of the hind legs, and there is severe
      demyelination in the peripheral nervous system including the presence of onion
      bulb formations. This approach will be valuable for pathologies produced by over
      expression of a gene including trisomy and amplification in cancer. Such models
      will be particularly useful for testing gene therapy approaches if the transgene
      is human.

PMID- 8733122
TI  - Characterization of the split hand/split foot malformation locus SHFM1 at 7q21.3
      q22.1 and analysis of a candidate gene for its expression during limb
      development.
AB  - Split hand/split foot malformation (SHFM) is a heterogeneous limb developmental
      disorder, characterized by missing digits and fusion of remaining digits. An
      autosomal dominant form of this disorder (SHFM1) has been mapped to 7q21.3-q22.1
      on the basis of SHFM-associated chromosomal rearrangements. Utilizing a YAC
      contig across this region, we have defined a critical interval of 1.5 Mb by the
      analysis of six interstitial deletion patients and mapped the translocation
      breakpoints of seven ectrodactyly patients within the interval. To delineate the
      basic molecular defect underlying SHFM, we have searched for candidate genes in a
      500 kb region containing five of the translocation breakpoints. Three genes were
      identified, two genes of the Distal-less (dii) homeobox gene family, DLX5 and
      DLX6 and a novel gene, which we named DSS1. DSS1 is predicted to encode a highly
      acidic polypeptide with no significant similarity to any known proteins but 100%
      amino acid sequence identify with its murine homolog (Dss1). Using RNA in situ
      hybridization analysis, we detected a tissue-specific expression profile for Dss1
      in limb bud, craniofacial primordia and skin. A deficiency in expression of Dss1,
      DLX5 and/or DLX6 during development may explain the SHFM phenotypes.

PMID- 8733123
TI  - Identification of the first gene (FRG1) from the FSHD region on human chromosome
      4q35.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant,
      neuromuscular disorder characterized by progressive weakness of muscles in the
      face, shoulder and upper arm. Deletion of integral copies of a 3.3 kb repeated
      unit from the subtelomeric region on chromosome 4q35 has been shown to be
      associated with FSHD. These repeated units which are apparently not transcribed,
      map very close to the 4q telomere and belong to a 3.3 kb repeat family dispersed
      over heterochromatic regions of the genome. Hence, position effect variegation
      (PEV), inducing allele-specific transcriptional repression of a gene located more
      centromeric, has been postulated as the underlying genetic mechanism of FSHD.
      This hypothesis has directed the search for the FSHD gene to the region
      centromeric to the repeated units. A CpG island was identified and found to be
      associated with the 5' untranslated region of a novel human gene, FRG1 (FSHD
      Region Gene 1). This evolutionary conserved gene is located about 100 kb proximal
      to the repeated units and belongs to a multigene family with FRG1 related
      sequences on multiple chromosomes. The mature chromosome 4 FRG1 transcript is
      1042 bp in length and contains nine exons which encode a putative protein of 258
      amino acid residues. Transcription of FRG1 was detected in several human tissues
      including placenta, lymphocytes, brain and muscle. To investigate a possible PEV
      mechanism, allele-specific FRG1 steady-state transcript levels were determined
      using RNA-based single-strand conformation polymorphism (SSCP) analysis. A
      polymorphic fragment contained within the first exon of FRG1 was amplified from
      reverse transcribed RNA from lymphocytes and muscle biopsies of patients and
      controls. No evidence for PEV mediated repression of allelic transcription was
      obtained in these tissues. However, detection of PEV in FSHD patients may require
      analysis of more specific cell types at particular developmental stages.

PMID- 8733124
TI  - Gene transfer into the mouse retina mediated by an adeno-associated viral vector.
AB  - Gene transfer to photoreceptor cells may provide a means for arresting the
      retinal degeneration that is characteristic of many inherited causes of
      blindness, including retinitis pigmentosa (RP). However, transduction of
      photoreceptors has to date been inefficient, and further limited by toxicity and
      immune responses directed against vector-specific proteins. An alternative vector
      system based on adeno-associated virus (AAV) may obviate these problems, and may
      be useful for transduction of neuronal cells. In this study we have demonstrated
      successful transduction of all layers of the neuroretina as well as the retinal
      pigment epithelium (RPE) following subretinal injection of recombinant AAV
      particles encoding lac Z. Furthermore, the efficiency of transduction of
      photoreceptors is significantly higher than that achieved with an equivalent
      adenoviral vector. This is the first report showing that AAV is capable of
      transducing photoreceptor cells and supports the use of this vector system for
      gene therapy of retinal diseases such as RP.

PMID- 8733125
TI  - Isolation of genes amplified in human cancers by microdissection mediated cDNA
      capture.
AB  - It has been increasingly recognized that homogeneously staining regions (hsr) in
      human cancers may be complex structures composed of large amplified DNA domains
      containing multiple genes. It is therefore important to devise strategies for the
      rapid isolation of cDNAs expressed from these structures. Using a procedure we
      term microdissection mediated cDNA capture, we recovered hsr specific cDNAs from
      two different human tumors. The glioblastoma cell line TX3868 and the human
      sarcoma cell line OsA-CL carry hsrs containing amplified sequences from
      chromosome 12q13-15. We recovered 17 hsr specific cDNAs following microdissection
      of these hsrs which had been previously hybridized in situ with linkered cDNA.
      Northern blot analysis with these cDNAs revealed hybridization to distinct
      transcripts in OsA-CL RNA and TX3868 RNA. None of the OsA-CL cDNA clones showed
      cross hybridization with the TX3868 cDNAs suggesting that despite their
      coincident band localization on 12q, the OsA-CL and TX3868 amplification units do
      not completely overlap. These results significantly increase the number of
      amplified genes assigned to the 12q13-15 amplicon illustrating both the
      complexity of hsrs derived from this region and the utility of microdissection
      mediated cDNA capture to gain rapid access to cDNAs transcribed from amplified
      genes.

PMID- 8733126
TI  - Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and
      sporadic hypoparathyroidism.
AB  - Parathyroid hormone secretion is negatively regulated by a 7-transmembrane
      domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that
      activating mutations in this receptor might cause autosomal dominant
      hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified, in two
      families with ADHP, heterozygous missense mutations in the Ca(2+)-sensing
      receptor gene that cosegregated with the disorder. None of 50 normal controls had
      either mutation. We also identified a de novo, missense Ca(2+)-sensing receptor
      mutation in a child with severe sporadic hypoparathyroidism. The amino acid
      substitution in one ADHP family affected the N-terminal, extracellular domain of
      the receptor. The other mutations involved the transmembrane region. Unlike
      patients with acquired hypoparathyroidism, patients with these mutations had
      hypercalciuria even at low serum calcium concentrations. Their greater
      hypercalciuria presumably reflected activation of Ca(2+)-sensing receptors in
      kidney cells, where the receptor negatively regulates calcium reabsorption. This
      augmented hypercalciuria increases the risk of renal complications and thus has
      implications for the choice of therapy.

PMID- 8733127
TI  - cDNA cloning of a human homologue of the Caenorhabditis elegans cell fate
      determining gene mab-21: expression, chromosomal localization and analysis of a
      highly polymorphic (CAG)n trinucleotide repeat.
AB  - The two most consistent features of the diseases caused by trinucleotide repeat
      expansion-neuropsychiatric symptoms and the phenomenon of genetic anticipation
      may be present in forms of dementia, hereditary ataxia, Parkinsonism, bipolar
      affective disorder, schizophrenia and autism. To identify candidate genes for
      these disorders, we have screened human brain cDNA libraries for the presence of
      gene fragments containing polymorphic trinucleotide repeats. Here we report the
      cDNA cloning of CAGR1, originally detected in a retinal cDNA library. The 2743 bp
      cDNA contains a 1077 bp open reading frame encoding 359 amino acids. This amino
      acid sequence is homologous (56% amino acid identify and 81% amino acid
      conservation) to the Caenorhabditis elegans cell fate-determining protein mab-21.
      CAGR1 is expressed in several human tissues, most prominently in the cerebellum,
      as a message of approximately 3.0 kb. The gene was mapped to 13q13, just
      telomeric to D13S220. A 5'-untranslated CAG trinucleotide repeat is highly
      polymorphic, with repeat length ranging from six to 31 triplets and a
      heterozygosity of 87-88% in 684 chromosomes from several human populations. One
      allele from an individual with an atypical movement disorder and bipolar
      affective disorder type II contains 46 triplets, 15 triplets longer than any
      other allele detected. Though insufficient data are available to link the long
      repeat to this clinical phenotype, an expansion mutation of the CAGR1 repeat can
      be considered a candidate for the etiology of disorders with anticipation or
      developmental abnormalities, and particularly any such disorders linked to
      chromosome 13.

PMID- 8733128
TI  - Isolation of a new clathrin heavy chain gene with muscle-specific expression from
      the region commonly deleted in velo-cardio-facial syndrome.
AB  - Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DGS) are developmental
      disorders characterized by a spectrum of phenotypes including velopharyngeal
      insufficiency, conotruncal heart defects and facial dysmorphology among others.
      Eighty to eighty-five percent of VCFS/DGS patients are hemizygous for a portion
      of chromosome 22. It is likely that the genes encoded by this region play a role
      in the etiology of the phenotypes associated with the disorders. Using a cDNA
      selection protocol, we isolated a novel clathrin heavy chain cDNA (CLTD) from the
      VCFS/DGS minimally deleted interval. The cDNA encodes a protein of 1638 amino
      acids. CLTD shares significant homology, but is not identical to the ubiquitously
      expressed clathrin heavy chain gene. The CLTD gene also shows a unique pattern of
      expression, having its maximal level of expression in skeletal muscle.
      Velopharyngeal insufficiency and muscle weakness are common features of VCFS
      patients. Based on the location and expression pattern of CLTD, we suggest
      hemizygosity at this locus may play a role in the etiology of one of the VCFS
      associated phenotypes.

PMID- 8733129
TI  - Characterization of a second human clathrin heavy chain polypeptide gene (CLH-22)
      from chromosome 22q11.
AB  - We report cloning and characterization of the second human clathrin heavy chain
      polypeptide gene (CLH-22) localized to chromosome 22q11. Hence H. sapiens is the
      first species for which two clathrin heavy chain genes have been reported. We
      provide 5470 bp cDNA sequence covering the entire open reading frame of the CLH
      22 gene. The predicted polypeptide is composed of 1640 amino acids. Its 6 kb
      transcript is expressed in all of 16 tested human tissues, suggesting it is a
      housekeeping gene. Skeletal muscle, testis and heart show significantly higher
      expression levels. Compared to the previously characterized human clathrin heavy
      chain gene localized on chromosome 17 (CLH-17), CLH-22 shows different transcript
      size and expression profile in human tissues. Northern analysis of CLH-22
      suggests that several alternatively spliced transcripts exist. A presumably
      single, 171 bp long alternatively spliced exon has been characterized. Amino acid
      sequence comparison between CLH-22 and CLH-17 shows an overall identify and
      similarity of 84.7 and 91.1%, respectively. At the nucleic acid level, identity
      between open reading frames of both genes is 74.3%. Sequence comparison with
      previously cloned genes in other species suggests that counterparts of the CLH-17
      gene have been cloned in B. taurus and R. norvegicus, whereas presumptive
      mammalian homologues of the CLH-22 gene are yet to be characterized. Our Northern
      and Southern blot analyses of meningiomas clearly suggest the CLH-22 gene may be
      involved in the tumor development and can be considered as a candidate for a
      tumor suppressor.

PMID- 8733130
TI  - Isolation of a novel gene from the DiGeorge syndrome critical region with
      homology to Drosophila gdl and to human LAMC1 genes.
AB  - DiGeorge syndrome, and more widely the CATCH 22 syndrome, are associated with
      microdeletions in chromosomal region 22q11.2. A critical region of 500 kb has
      been delimited within which maps the breakpoint of a balanced translocation
      associated with mild CATCH 22 phenotypes. We report the isolation from this
      critical region of a novel gene, DGCR6, which maps 115 kb centromeric to the
      balanced translocation breakpoint. The DGCR6 gene product shares homology with
      the Drosophila melanogaster gonadal protein, which participates in gonadal and
      germ-line cells development, and with the human laminin. gamma-1 chain, which
      upon polymerization with alpha- and beta- chains forms the laminin molecule.
      Laminin binds to cells through interaction with a receptor and has functions in
      cell attachment, migration and tissue organization during development. DGCR6
      could be a candidate for involvement in the DiGeorge syndrome pathology by
      playing a role in neural crest cell migration into the third and fourth
      pharyngeal pouches, the structures from which derive the organs affected in
      DiGeorge syndrome.

PMID- 8733131
TI  - Expression of the von Hippel-Lindau disease tumour suppressor gene during human
      embryogenesis.
AB  - The von Hippel-Lindau (VHL) disease product is thought to down-regulate
      transcription by antagonizing elongin-enhanced transcriptional elongation.
      Germline VHL gene mutations predispose to the development of retinal, cerebellar
      and spinal haemangioblastomas, renal cell carcinoma and phaeochromocytoma. In
      addition, somatic Inactivation of the VHL gene is frequent in sporadic renal cell
      carcinoma and haemangioblastoma. Regulation of transcript elongation is an
      important control mechanism for gene expression and the VHL gene might modify the
      expression of proto-oncogenes and growth suppressor genes during embryogenesis.
      We therefore investigated the expression of VHL mRNA during human embryogenesis
      by in situ hybridization studies at 4, 6 and 10 weeks post conception. Although
      VHL mRNA was expressed in all three germ layers, strong expression was noted in
      the central nervous system, kidneys, testis and lung. Within the kidney, VHL mRNA
      was differentially expressed within renal tubules suggesting that the VHL gene
      product may have a specific role in kidney development. Two alternatively spliced
      VHL mRNAs characterized by inclusion (isoform I) or exclusion (isoform II) of
      exon 2 are transcribed in adult tissues. To investigate if the two isoforms are
      differentially expressed during embryogenesis, VHL mRNA was reverse transcribed
      from 13 fetal tissues (8-10 weeks gestation). The quantitative distribution of
      VHL mRNA within fetal tissues reflected that seen by in situ hybridization and
      the ratio of the two VHL isoforms was similar between tissues. Although the genes
      regulated by the VHL gene product have not yet been identified, our findings are
      compatible with the hypothesis that VHL-mediated control of transcriptional
      elongation may have a role in normal human development.

PMID- 8733132
TI  - Crigler-Najjar syndrome type II is inherited both as a dominant and as a
      recessive trait.
AB  - Crigler-Najjar syndrome type II (CN-II) is caused by a severely reduced hepatic
      activity of bilirubin UDP-glucuronosyltransferase (UGT). Recently, by the
      analysis of the genetic background of CN-II patients, it has been clarified that
      the patients carry homozygous missense mutations or nonsense plus missense
      mutations on the gene for UGT, and CN-II was inherited as an autosomal recessive
      trait. We encountered a new case which had a nonsense mutation caused by a single
      nucleotide substitution on one allele. This indicates that CN-II is also
      inherited as a dominant trait as well as a recessive trait. Expression study in
      vitro strongly suggests that the disease in this case is caused by a dominant
      negative mutation by forming a heterologous subunit structure.

PMID- 8733133
TI  - X-linked liver glycogenosis type II (XLG II) is caused by mutations in PHKA2, the
      gene encoding the liver alpha subunit of phosphorylase kinase.
AB  - X-linked liver glycogenosis type II (XLG II) is a recently described X-linked
      liver glycogen storage disease, mainly characterized by enlarged liver and growth
      retardation. These clinical symptoms are very similar to those of XLG I. In
      contrast to XLG I patients, however, XLG II patients do not show an in vitro
      enzymatic deficiency of phosphorylase kinase (PHK). Recently, mutations were
      identified in the gene encoding the liver alpha subunit of PHK (PHKA2) in XLG I
      patients. We have now studied the PHKA2 gene of four unrelated XLG II patients
      and identified four different mutations in the open reading frame, including a
      deletion of three nucleotides, an insertion of six nucleotides and two missense
      mutations. These results indicate that XLG II is due to mutations in PHKA2. In
      contrast to XLG I, XLG II is caused by mutations that lead to minor structural
      abnormalities in the primary structure of the liver alpha subunit of PHK. These
      mutations are found in a conserved RXX(X)T motif, resembling known
      phosphorylation sites that might be involved in the regulation of PHK. These
      findings might explain why the in vitro PHK enzymatic activity is not deficient
      in XLG II, whereas it is in XLG I.

PMID- 8733134
TI  - Mutation hotspots in the PHKA2 gene in X-linked liver glycogenosis due to
      phosphorylase kinase deficiency with atypical activity in blood cells (XLG2).
AB  - In five cases of X-linked liver glycogenosis subtype 2 (XLG2), we have identified
      mutations in the gene encoding the liver isoform of the phosphorylase kinase
      alpha subunit (PHKA2). XLG2 is a rare variant of X-linked phosphorylase kinase
      (Phk) deficiency of the liver. Whereas in the more common form of X-linked
      hepatic Phk deficiency, XLG1, the enzyme's activity is decreased both in liver
      and in blood cells, Phk activity in XLG2 is low in liver but normal or even
      enhanced in blood cells. Although missense, nonsense and splicesite mutations in
      the PHKA2 gene were recently identified in several cases of XLG1, no mutations
      have yet been described for XLG2 and a molecular explanation for the peculiar
      biochemical phenotype of XLG2 has been lacking. All mutations found in the
      present study result in non-conservative amino acid replacements of residues that
      are absolutely conserved between the alpha L, alpha M and beta subunits of Phk
      [H132P, H132Y, R186H (twice) and D299G]. Strikingly, in two pairs of cases the
      mutations affect the same codon. These results demonstrate that: (i) XLG2 is
      caused by mutations in PHKA2 and is therefore allelic with XLG1; and (ii) XLG2
      mutations appear to cluster in limited sequence regions or even individual
      codons.

PMID- 8733135
TI  - Long-range sequence analysis in Xq28: thirteen known and six candidate genes in
      219.4 kb of high GC DNA between the RCP/GCP and G6PD loci.
AB  - DNA comprising 219 447 bp was sequenced in nine cosmids and verified at > 99.9%
      precision. Of the standard repetitive elements, 187 Alus make up 20.6% of the
      sequence, but there were only 27 MERs (2.9%) and 17 L1 fragments (1.6%). This may
      be characteristic of such high GC (57%) regions. The sequence also includes an
      11.3 kb tract duplicated with 99.2% identity at a distance of 38 kb. The region
      is 80-90% transcribed and 12.5% translated. Thirteen known genes and their exon
      intron borders are all accurately predicted at least in part by GRAIL programs,
      as are six additional genes. From centromere to telomere, the orientation of
      transcription varies among the first eight genes, then runs centromeric to
      telomeric for the next five, and is in the opposite sense for the last six.
      Eighteen of the 19 genes are associated with CpG islands. Two islands are exact
      copies in the 11.3 kb repeat units, and could thus give rise to double dosage
      levels of an X-linked gene. Another island is associated with two genes
      transcribed in opposite directions. From the sequence data, three genes and their
      exon structure are inferred. One of them, previously associated with HEX2, is
      shown to be a different gene unrelated to hexokinases; a second gene, previously
      known by an EST, is plexin, from its 65.5% identity with the Xenopus analog; and
      a third is a subunit of a vacuolar H-ATPase, and is named VATPS1.

PMID- 8733136
TI  - Genetic mapping of the human homologue (T) of mouse T(Brachyury) and a search for
      allele association between human T and spina bifida.
AB  - We describe a genetic analysis of the human homologue (T) of the mouse T
      (Brachyury) gene; human T was recently cloned in our laboratory. The protein
      product of the T gene is a transcription factor crucial in vertebrates for the
      formation of normal mesoderm. T mutant Brachyury mice die in midgestation with
      severe defects in posterior mesodermal tissues; heterozygous mice are viable but
      have posterior axial malformations. In addition to its importance in development,
      T has intrigued geneticists because of its association with the mouse t
      haplotype; this haplotype is a variant form of the t-complex and is characterized
      by transmission ratio distortion, male sterility and recombination suppression.
      We have identified a common polymorphism of human T by single strand conformation
      polymorphism (SSCP) and used this in mapping studies and to re-investigate the
      idea that human T is involved in susceptibility to the multifactorial, neural
      tube defect, spina bifida. Our mapping data show that human T maps to 6q27 and
      lies between two other genes of the t-complex, TCP1 and TCP10. These data add to
      the evidence that in man the genes of the t-complex are split into two main
      locations on the short and long arms of chromosome 6. We have used an allele
      association test which is independent of mode of inheritance and penetrance to
      analyse data from the spina bifida families. Using this test we find evidence for
      a significant (p = 0.02) association between transmission of the TIVS7-2 allele
      of the human T gene and spina bifida.

PMID- 8733137
TI  - A member of the MAP kinase phosphatase gene family in mouse containing a complex
      trinucleotide repeat in the coding region.
AB  - We have identified a novel mouse gene encoding a protein that shows high homology
      to the dual-specificity tyrosine/threonine phosphatase family of proteins. The
      gene encodes a 5 kb transcript which is expressed predominantly in brain and lung
      and contains a translated complex trinucleotide repeat within the coding region.
      Using interspecific mouse backcross analysis, the gene has been localised to
      distal mouse chromosome 7. In human, homologous sequences are located in the
      syntenic region on distal chromosome 11p as well as to chromosome 10q11.2 and
      10q22. The presence of a CG-rich trinucleotide repeat in the coding region
      provides a target for mutation which might result in loss of function or altered
      properties of this phosphatase.

PMID- 8733138
TI  - Heterogeneity in telomere length of human chromosomes.
AB  - Vertebrate chromosomes terminate in variable numbers of T2AG3 nucleotide repeats.
      In order to study telomere repeats at individual chromosomes, we developed novel,
      quantitative fluorescence in situ hybridization procedures using labeled (C3TA2)3
      peptide nucleic acid and digital imaging microscopy. Telomere fluorescence
      intensity values from metaphase chromosomes of cultured human hematopoietic cells
      decreased with the replication history of the cells, varied up to six-fold within
      a metaphase, and were similar between sister chromatid telomeres. Surprisingly,
      telomere fluorescence intensity values within normal adult bone marrow metaphases
      did not show a normal distribution, suggesting that a minimum number of repeats
      at each telomere is required and/or maintained during normal hematopoiesis.

PMID- 8733139
TI  - Confirmation of three susceptibility genes to insulin-dependent diabetes
      mellitus: IDDM4, IDDM5 and IDDM8.
AB  - Previous genome-wide mapping studies have provided suggestive linkage evidence
      for several novel susceptibility loci responsible for insulin-dependent diabetes
      mellitus (IDDM); however, the evidence was not sufficient to confirm the
      existence of these genes. We analyzed 265 Caucasian families with IDDM and report
      the first evidence that meets the standard for confirmed linkage for three
      susceptibility loci. The maximum LOD scores (MLS) were 3.9, 4.5 and 3.6 in our
      data set, and 5.0, 4.6 and 5.0 for our data combined with non-overlapping data
      from the literature, for IDDM4 on chromosome 11q13, IDDM5 on 6q25, and IDDM8 on
      6q27, respectively. However, we could not confirm linkage for IDDM3 on 15q26 and
      IDDM7 on 2q31-q33, or linkage disequilibrium between D2S152 and IDDM7.

PMID- 8733140
TI  - Linkage of polymorphic congenital cataract to the gamma-crystallin gene locus on
      human chromosome 2q33-35.
AB  - Cataract is one of the major causes of blindness in humans. We describe here an
      autosomal dominant polymorphic congenital cataract (PCC) which is characterised
      by wide variations in phenotype of non-nuclear lens opacities, even among
      affected members of the same family. PCC families included a large, unique
      pedigree (254 members, 103 affected individuals), and genetic linkage was
      conducted using a variety of polymorphic markers. Evidence for linkage was found
      for chromosome 2q33-35 with PCC mapping near D2S72 and TNP1. A tri-nucleotide
      microsatellite marker for gamma-crystallin B gene (CRYG1) was found to co
      segregate with PCC and yielded a maximum lod score of 10.62 at (theta = 0). A
      multipoint analysis demonstrated that the most probable location of the PCC gene
      was within an 8 cM genetic interval containing the gamma-crystallin gene cluster.
      These data provide strong evidence of the existence of an autosomal dominant
      mutation for PCC in or near the gamma-crystallin gene cluster. This defect is
      characterised by complete penetrance but variable expression of the cataract
      phenotype. Our study also suggests that non-nuclear human cataracts might be
      caused by some abnormality in gamma-crystallin genes.

PMID- 8733142
TI  - Invariance and constancy in vision.

PMID- 8733141
TI  - Localisation of a gene for central areolar choroidal dystrophy to chromosome 17p.
AB  - Central areolar choroidal dystrophy (CACD) is a rare inherited retinal disease
      which causes progressive profound loss of vision in patients during their 4th
      decade. We have identified a Northern Irish family with 19 affected individuals
      in three living generations. We have performed a total genome search and
      established linkage of CACD in this family to chromosome 17p (multipoint Zmax =
      5.65 at D17S938). The genes for phosphatidylinositol transfer protein (PITPN),
      retinal guanylate cyclase (GUC2D), beta-arrestin 2 (ARRB2), pigment epithelium
      derived factor (PEDF) and recoverin (RCV1) map to this region and are candidate
      genes for retinal disease. Analysis of the coding region of the PITPN gene failed
      to reveal any mutation in this family.

PMID- 8733143
TI  - Evidence for good recovery of lengths of real objects seen with natural stereo
      viewing.
AB  - Six experiments are described in which good performance of the task of matching
      the lengths of two stationary real objects, gnarled wooden sticks, under a
      variety of binocular viewing conditions, including variations in viewing
      distances was demonstrated. Relatively poor matching performance was observed
      when the sticks were viewed monocularly in oscillatory motion, or monocularly and
      stationary. The results suggest that stereo can support good representations of
      metric scene structure when length judgments of natural objects are required
      under (quasi-)natural viewing. The implications of these results for theories of
      structure from stereo and structure from motion are discussed.

PMID- 8733144
TI  - Shape constancy in pictorial relief.
AB  - Pictorial relief was measured for a series of pictures of a smooth solid object.
      The scene was geometrically identical (ie the perspective of the three
      dimensional scene remained the same) for all pictures, the rendering different.
      Some of the pictures were monochrome full-scale photographs taken under different
      illumination of the scene. Also included were a silhouette (uniform black on
      uniform white) and a 'cartoon'-style rendering (visual contour and key linear
      features rendered in thin black line on a uniform white ground). Two subjects
      were naive and started with the silhouette, saw the cartoon next, and finally the
      full-scale photographs. Another subject had seen the object and did the
      experiment in the opposite sequence. The silhouette rendering is impoverished,
      but has considerable relief with much of the basic shape. The cartoon rendering
      yields well-developed pictorial relief, even for the naive subjects. Shading adds
      only small local details, but different illumination produces significant
      alterations of relief. It is concluded that shape constancy under changes in
      illumination is dominant throughout, but that the (small) deviations from true
      constancy reveal the effect of cues such as shading in a natural setting. Such a
      ?perturbation analysis' appears more promising than either stimulus-reduction or
      cue-conflict paradigms.

PMID- 8733145
TI  - Pooling of vertical disparities by the human visual system.
AB  - Two experiments are described in which the effects of scaling vertical
      disparities on the perceived amplitudes of dome-shaped surfaces depicted with
      horizontal disparities were examined. The Mayhew and Longuet-Higgins's theory and
      the regional-disparity-correction theory of Garding et al predict that scaling
      should generate a change in perceived depth appropriate to the viewing distance
      simulated by the scaled vertical disparities. Significant depth changes were
      observed, by means of a nulling task in which the vertical-disparity-scaling
      effect was cancelled by the observer choosing a pattern of horizontal disparities
      that made the dome-shaped surface appear flat. The sizes of the scaling effects
      were less than those predicted by either theory, suggesting that other cues to
      fixation distance such as oculomotor information played an appreciable role. In
      conditions in which 50% of the texture elements were given one value of vertical
      disparity scaling and the remaining 50% were left unscaled, the size of the
      scaling effect on perceived depth could be accounted for by equally weighted
      pooling of the vertical-disparity information unless the two scalings were very
      dissimilar, in which case the lower scaling factor tended to dominate. These
      findings are discussed in terms of a Hough parameter estimation model of the
      vertical-disparity-pooling process.

PMID- 8733146
TI  - The depiction of distance: a Bartelian analysis.
AB  - Work by Bartel has shown that observers make systematic errors when attempting to
      set a receding row of staves at equal intervals, and make even-more-pronounced
      errors in the same direction when drawing a similar row; consequently, the
      factors that contribute to this systematic distortion in spatial representation
      were examined. The results indicate that the tendency to overestimate nearer
      distances and underestimate further distances in pictorial space may be enhanced
      both by increasing the size ratio of the nearest and furthest pictorial elements
      and by increasing the angle of convergence of represented parallel contours.
      However, it is clear that size ratio is the more powerful independent variable.
      The reasons for this discrepancy are discussed and an explanation of the pattern
      of pictorial distortion, in terms of a compromise between an objective
      representation of the relative estimated distance of the depicted distances and
      an inaccurately anticipated optical projection, is proffered.

PMID- 8733147
TI  - A general model for the perception of space and motion.
AB  - The perception of space and motion involves successive transformations of signals
      with respect to different reference systems. The visual input is coded in terms
      of retinal coordinates. The retinocentric values from each eye require to be
      unified, and to be combined with signals for eye position and movement. This
      egocentric reference provides a signal for the angular size, motion, or
      orientation of the stimulus with respect to the observer. The egocentric signals
      are transformed to a coordinate system that is three-dimensional-the geocentric
      frame of reference. Further transformations can occur at earlier levels owing to
      patterncentric interactions within the visual field. When the geocentric signal
      corresponds to the physical dimensions of space and motion, this is referred to
      as perceptual constancy.

PMID- 8733148
TI  - Qualitative cues in the discrimination of affine-transformed minimal patterns.
AB  - An important factor in judging whether two retinal images arise from the same
      object viewed from different positions may be the presence of certain properties
      or cues that are 'qualitative invariants' with respect to the natural
      transformations, particularly affine transformations, associated with changes in
      viewpoint. To test whether observers use certain affine qualitative cues such as
      concavity, convexity, collinearity, and parallelism of the image elements, a
      'same-different' discrimination experiment was carried out with planar patterns
      that were defined by four points either connected by straight line segments (line
      patterns) or marked by dots (dot patterns). The first three points of each
      pattern were generated randomly; the fourth point fell on their diagonal
      bisector. According to the position of that point, the patterns were concave,
      triangular (three points being collinear), convex, or parallel sided. In a 'same'
      trial, an affine transformation was applied to one of two identical patterns; in
      a 'different' trial, the affine transformation was applied after the point lying
      on the diagonal bisector was perturbed a short, fixed distance along the
      bisector, inwards for one pattern and outwards for the other. Observers' ability
      to discriminate 'same' from 'different' pairs of patterns depended strongly on
      the position of the fourth, displaced, point: performance varied rapidly when the
      position of the displaced point was such that the patterns were nearly triangular
      or nearly parallel sided, consistent with observers using the hypothesised
      qualitative cues. The experimental data were fitted with a simple probabilistic
      model of discrimination performance that used a combination of these qualitative
      cues and a single quantitative cue.

PMID- 8733149
TI  - A canonical microfunction for learning perceptual invariances.
AB  - An unsupervised method is presented which permits a set of model neurons, or a
      microcircuit, to learn low-level vision tasks, such as the extraction of surface
      depth. Each micro-circuit implements a simple, generic strategy which is based on
      a key assumption: perceptually salient visual invariances, such as surface depth,
      vary smoothly over time. In the process of learning to extract smoothly varying
      invariances, each microcircuit maximises a microfunction. This is achieved by
      means of a learning rule which maximises the long-term variance of the state of a
      model neuron and simultaneously minimises its short-term variance. The learning
      rule involves a linear combination of anti-Hebbian and Hebbian weight changes,
      over short and long time scales, respectively. The method is demonstrated on a
      hyperacuity task: estimating subpixel stereo disparity from a temporal sequence
      of random-dot stereograms. After learning, the micro-circuit generalises, without
      additional learning, to previously unseen image sequences. It is proposed that
      the approach adopted here may be used to define a canonical microfunction, which
      can be used to learn many perceptually salient invariances.

PMID- 8733150
TI  - Dependence of relational colour constancy on the extraction of a transient
      signal.
AB  - Human observers can correctly attribute changes in the appearance of a scene
      either to changes in the incident light or to changes in the spectral-reflectance
      properties of the scene. This ability was assessed as a function of the time
      course of illuminant and spectral-reflectance changes. Observers were presented
      with computer simulations of Mondrian patterns of 49 randomly selected Munsell
      papers. On each trial a Mondrian pattern was presented for 1 s; the pattern then
      changed either instantaneously or gradually into another Mondrian pattern, also
      presented for 1 s, which was related to the first either by an illuminant change
      or by an illuminant change accompanied by additional changes in the spectral
      reflectance functions of the individual papers. Illuminant and spectral
      reflectance change were applied linearly in time (with respect to CIE
      coordinates) over intervals ranging from 0 to 7 s. Observers indicated whether
      there was a spectral-reflectance change. They were able to make reliable
      discriminations between illuminant and spectral-reflectance changes both when the
      changes were applied instantaneously and when they were applied gradually over
      time, but performance worsened progressively as the duration of the changes
      increased, that is, as their rate decreased. It is suggested that discrimination
      in this task depends on the extraction of a low-level transient signal which is
      generated in response to rapid changes in scene appearance and which is
      progressively attenuated as changes occur more and more gradually.

PMID- 8733151
TI  - Measurements of colour constancy by using a forced-choice matching technique.
AB  - Colour constancy is typically measured with techniques involving asymmetric
      matching by adjustment, in which the observer views two scenes under different
      illuminants and adjusts the colour of a reference patch in one to match a test
      patch in the other. This technique involves an unnatural task, requiring the
      observer to predict and adjust colour appearance under an illumination shift.
      Natural colour constancy is more a simple matter of determining whether a colour
      is the same as or different from that seen under different illumination
      conditions. There are also technical disadvantages to the method of matching by
      adjustment, particularly when used to measure colour constancy in complex scenes.
      Therefore, we have developed and tested a two-dimensional method of constant
      stimuli, forced-choice matching paradigm for measuring colour constancy.
      Observers view test and reference scenes haploscopically and simultaneously, each
      eye maintaining separate adaptation throughout a session. On each trial, a pair
      of test and reference patches against multicoloured backgrounds are presented,
      the reference patch colours being selected from a two-dimensional grid of
      displayable colours around the point of perfect colour constancy. The observer's
      task is to respond "same" or "different". Fitting a two-dimensional Gaussian to
      the percentage of "different" responses yields (1) the subjective colour
      constancy point, (2) the discrimination ellipse centred on this point, and (3) a
      map of changes in sensitivity to chromatic differences induced by the illuminant
      shift. The subjective colour-constancy point measured in this way shows smaller
      deviations from perfect colour constancy-under conditions of monocular adaptation
      than previously reported; discrimination ellipses are several times larger than
      standard MacAdam ellipses; and chromatic sensitivity is independent of the
      direction of the illuminant shift, for broad distributions of background colours.

PMID- 8733152
TI  - The goldfish--a colour-constant animal.
AB  - A series of either thirteen or fifteen coloured test fields with hues from blue
      through grey to yellow were presented on a black background. Goldfish were
      trained on a bluish-grey test field by food reward. In the training situation,
      the setup with the coloured papers was illuminated with white light. In the test
      situation, the colour of the illumination was changed to blue or yellow. In both
      test illuminations the goldfish preferred the training field in the same way as
      under white illumination despite the fact that this test field stimulated the
      cone types very differently from the training situation. As test fields were
      present that excited the cones in exactly the same way as under white light, but
      were not chosen, colour constancy can be concluded. By means of colour metrics,
      it was possible to quantify direction and strength of colour constancy.

PMID- 8733153
TI  - Is electron-transfer from glutamate receptors or other plasma membrane ionic
      channels involved in oxidative stress and neurodegenerative diseases?
AB  - There is theoretical evidence that biopolymers such as proteins can have
      semiconductor properties, with electrons (and holes) that can move inside the
      macromolecule. Double layers of charge can thus be formed at the plasma membrane
      protein interface with the electrolytes. Electron-transfer can occur at such
      interfaces too, and electrons can participate in charge transport processes
      across the biopolymer from one side of the plasma membrane to the other. These
      phenomena are studied here in the pathological case when the average equilibrium
      in the electron-transfer process at the cytoplasmic interface suffers a continued
      offset that leads to free-radical formation inside the cell. This would help in
      the long term to increase oxidative stress inside the cell, and would thus
      contribute to the appearance of neurodegenerative diseases.

PMID- 8733154
TI  - A theoretical approach to the contribution and significance of physiological
      antiepileptic systems in the clinical manifestations of epileptic symptoms.
AB  - The onset an of epileptic seizure is the most striking event in the
      pathophysiology of epilepsy from the clinical aspect. Present knowledge
      concerning the pathomechanism of the disease does not explain why, in spite of a
      permanent epileptic dysfunction, the occurrence of clinical seizures is
      relatively rare even in severe epilepsies. According to my hypothesis, the
      clinical picture is determined by the balance of two systems of opposite nature
      (i.e. epileptogenic and antiepileptic). Regarding these systems, research has
      focused exclusively on the former. A short survey is given here of everyday
      clinical and EEG experiences which cannot be explained on the basis of epileptic
      dysfunction and may therefore be considered as indirect evidence of the existence
      of a physiological antiepileptic system. The hypothesis may also help to explain
      some special events like occasional epileptic symptoms, 'positive'
      electroencephalography without clinical signs and the influence of provoking
      factors. It further clearly shows the place of nonpharmacological (psychological)
      treatments for epilepsy, stressing the importance of an holistic attitude.

PMID- 8733155
TI  - Sleep as vegetation: a tautological theory of sleep.
AB  - It is commonly assumed that sleep is secondary to the waking state. We consider
      that in evolution relational life, as represented by the waking state, was
      superimposed on vegetative life. Waking is periodic, and vegetation is manifest
      in the intervals. This vegetative phase takes the form of sleep. The model, which
      overturns the traditional view, offers new suggestions about the psychological
      and cultural conception of sleep, sleep and the brain, dreaming, mind and memory.

PMID- 8733156
TI  - Statisticodynamics of pairing between homologous chromatids in mammalian
      spermatogonia.
AB  - The paper studies how the Apollonian dynamics of clustered chromatids contributes
      to optimize pairing between homologs in mitosing mammalian spermatogonia,
      particularly so during anaphase.

PMID- 8733157
TI  - Microvesiculation of the microvilli provides a membranous medium within the lumen
      during digestion.
AB  - A hypothesis is presented which states that there is a membranous medium within
      the intestinal lumen which occurs during digestion. The medium is thought to be
      generated by the microvesiculation of the microvilli.

PMID- 8733158
TI  - Cortical simplicity and mental processes.
AB  - The cerebral cortex can be looked upon as a non-linear system of coupled
      oscillators that tries to resist desynchronization and seeks to optimize the
      activity distribution of its elements. Cortical self-optimization can be
      disturbed by incoming nervous activity and the cortex will compensate for it by
      reorganizing the state of the soma, thus producing behavior. This simple concept
      would not explain mental processes that run within the cortex. It is proposed to
      relate mental processes to somatic behavior. Emotions, visual images, dreams,
      thoughts, memories, and anticipations could be perceived from the activity of
      respiratory, orofacial, and eye muscles. In their basic nature, mental processes
      may not differ from auditory, visual or visceral sensations. It is the peripheral
      soma that determines our mind and behavior; the task of the cortex is to line up
      somatic states. This philosophy could provide a new framework for data and
      results emanating from different fields of the neuroscience.

PMID- 8733159
TI  - Mechanical optimization of bone.
AB  - In bending, the mechanical strength of tubular bone can be estimated by the area
      moment of inertia (I) = 1/4 x pi x (R4 - r4) (R: external radius, and r: internal
      radius). Mechanical strength of bone is dissociated from bone density, since
      radiological density is different from inertia. When the cross-sectional area is
      constant (C = R2 - r2) in this equation, inertia can be expressed by the equation
      of (I) = 1/4 x pi x (2Cr2 + C2). Inertia increases with increases of the external
      and internal radii. According to the above equation, increase of inertia
      depending on the expansion of radii is inevitable 'optimization' of bone mass.
      Expansion of the radii of tubular bone with the decrease of wall thickness is an
      adaptation process rather than the 'decompensation' called osteoporosis.
      Senescence of individuals as manifested in conditions such as osteoporosis is a
      stampede of adaptations rather than decompensation of it.

PMID- 8733160
TI  - Popular press diagnoses and psychiatric diagnoses.
AB  - The symptom spectra of several 'popular press' diagnoses are examined and
      compared to Diagnostic and Statistical Manual of Mental Disorders-IIIR criteria
      for somatization disorder, depression, and generalized anxiety disorder. While
      there is much overlap, there are clear distinctions, and these psychiatric terms
      do not adequately coincide with the symptom spectra of these disorders. These
      conditions may represent 'neuroendocrine dysrhythmias' - abnormal/normal
      physiological dysfunctions with psychodynamic roots and/or influences. They
      currently often fall between the established domains claimed by Medicine and
      Psychiatry, with resultant poor evaluation and management with this spectrum of
      problems.

PMID- 8733161
TI  - Fish oil may be an antidote for the cardiovascular risk of smoking.
AB  - The fact that the cardiovascular risk of ex-smokers approximates that of non
      smokers after two years of abstinence, implies that accelerated atherogenesis is
      not the chief mechanism of smoking-related heart disease. Indeed, smoking or
      nicotine have adverse effects on blood rheology, thrombotic risk, coronary blood
      flow, and risk for arrhythmias. Omega-3-rich fish oils can be expected to correct
      or compensate for a remarkable number of the adverse impacts of smoking/nicotine:
      increased plasma fibrinogen, decreased erythrocyte distensibility, increased
      plasma and blood viscosity, increased platelet aggregability, increased
      plasminogen activator inhibitor levels, vasoconstriction of the coronary bed,
      reduced fibrillation threshold, increased triglycerides, reduced high-density
      lipoprotein cholesterol, and increased production of superoxide by phagocytes.
      Smokers who cannot overcome their addiction should be encouraged to substitute
      nicotine aerosols/gum for tobacco and advised to use supplementary fish oil and
      other cardioprotective nutrients.

PMID- 8733162
TI  - Necrobiosis lipoidica and diabetic control revisited.
AB  - Necrobiosis lipoidica diabeticorum is a rare skin disorder, usually considered a
      marker for diabetes mellitus. More than half of the patients with necrobiosis
      lipoidica diabeticorum have diabetes mellitus, but less than one per cent of
      diabetes mellitus patients have necrobiosis lipoidica diabeticorum. In the
      diabetes and dermatology literature, we find the position that there is no effect
      of glucose control on either the appearance of necrobiosis lipoidica diabeticorum
      or the clinical course of the lesion. We base our challenge to this position on a
      critical review of the original data. And conclude on the contrary, that
      necrobiosis lipoidica diabeticorum is usually associated with poor glucose
      control and that tighter glucose control, as currently practised, might improve
      or prevent the disorder.

PMID- 8733163
TI  - Sporadic transmission of hepatitis C.
AB  - At the present time, people having contracted hepatitis C are not warned about
      the possible ways in which they can transmit this disease to others. This greatly
      increases the risk of sporadic transmission of the virus. Public health and
      medical authorities should institute programs to inform all such afflicted
      persons how to avoid communicating the disease to others.

PMID- 8733164
TI  - Oncogenic retroviruses of cattle, chickens and turkeys: potential infectivity and
      oncogenicity for humans.
AB  - Reticuloendotheliosis virus naturally infects and cause lymphoid leukosis in
      chickens and turkeys. We investigated whether it can infect/transfect a variety
      of human cells in vitro. Successful infection and transfection were achieved with
      limited replication of virus. These findings, together with the knowledge that
      other oncogenic retroviruses of chickens and cattle, viz. The avian
      leukosis/sarcoma viruses and bovine leukemia virus show similar
      infectivity/oncogencity in vitro for humans, and the recent demonstration of
      antibodies to avian leukosis/sarcoma virus and reticuloendotheliosis virus in
      human sera, suggest that these viruses may have a role in the etiology of certain
      cancers in humans. There is now urgent need to investigate this, particularly
      because recent epidemiological studies consistently demonstrate excess of cancers
      in groups occupationally exposed to these viruses.

PMID- 8733165
TI  - Dietary management of pancreatic beta-cell homeostasis and control of diabetes.
AB  - Undernutrition, overnutrition and malnutrition, in addition to several other
      environmental insults have been claimed to play roles in the etiopathogenesis of
      insulin-dependent and -independent diabetes. These factors are known to alter the
      beta-cell function and disturb its homeostasis, i.e. qualitative and quantitative
      changes in its activity. This can lead to disturbed glucose homeostasis and
      thereby diabetes. It is possible to stop this vicious cycle and reduce the
      incidence of diabetes by restoring the homeostasis of beta-cell function through
      proper diabetes management and maintainance of an appropriate dietary milieu. It
      has been suggested that beta-cell dysfunction or death occurs by oxyradical
      mediated processes. Adequate stimulation of beta cells through high carbohydrate
      and fibre intake, and reduced oxidative tone by caloric restriction (low protein
      and saturated fat), supplementation with antioxidants (vitamin E and D) and
      polyunsaturated essential fatty acids may prevent loss or even restore the beta
      cell activity from environmental diabetogenic insults.

PMID- 8733166
TI  - Schizophrenia, bacterial toxins and the genetics of redundancy.
AB  - The hypothesis proposed is that episodes of bacterial toxaemia occurring early in
      life cause subtle brain damage which predisposes to schizophrenia. The damage is
      most likely to occur in individuals who have one or more mutations in a large set
      of genes controlling aspects of the immune response to infection. These genes,
      numbering several hundreds or even thousands, control a vital but highly
      redundant system. Schizophrenia, by reducing fertility, causes selective pressure
      against the mutations which would otherwise accumulate in the genome and degrade
      our ability to fight infection. This hypothesis is consistent with the key
      features of the disease which include a strong genetic component, neuroanatomical
      abnormalities, a seasonal influence, lack of association with HLA subtypes and
      the observation that the frequency of schizophrenia is similar in widely
      different populations. If bacterial toxins also have a role in precipitating
      acute psychosis, then the age incidence of schizophrenia can be explained.

PMID- 8733167
TI  - Alzheimer's disease risk factors as related to cerebral blood flow.
AB  - Inconsistencies within results of case-control studies on Alzheimer's disease
      risk factors led to a search of the literature for a potential cofactor. Reduced
      cerebral blood flow was selected and literature was surveyed for evidence of a
      cerebral blood flow linkage with the more than 40 putative risks. Alcohol abuse,
      depression, head trauma, underactivity, old age, sleep disturbance, glucose
      utilization, Down's syndrome, and Parkinson's disease are risk factors where an
      association with reduced cerebral blood flow is documented. Studies were cited
      showing that improved cerebral blood flow is associated with factors thought to
      be helpful in Alzheimer's disease, such as education or occupational attainment,
      exercise, headache, smoking, and arthritis/anti-inflammatory drugs to the extent
      that aspirin is used. Sugar consumption is identified as a potential risk factor
      with glucose management in Alzheimer's disease also shown to involve reduced
      cerebral blood flow. An hypothesis is developed showing how compromised regional
      cerebral blood flow could fit as a cofactor for genetic, autoimmune, and
      neurotoxic aspects of Alzheimer's disease.

PMID- 8733168
TI  - Porphyria: a new perspective.
AB  - Recently, Medical Hypotheses has published two papers on fatigue syndromes and
      their relationship to porphyrin metabolism (1,2). This article continues the
      exploration of how many diseases may have abnormal porphyrin metabolism playing a
      role in their pathogenesis. Another issue is the need to expand our concepts of
      the frequencies of these genetic enzyme deficiencies in this pathway. Over time
      and the development of better tests, the identification of porphyric patients has
      increased (3). Now that more enzymes are becoming available for testing, the use
      and interpretation of those tests becomes critical and the selection of control
      populations could greatly affect results.

PMID- 8733169
TI  - Sudden infant death syndrome: near-weightlessness and delayed neural
      transformation.
AB  - Dilation of the pulmonary arteries and increased pulmonary blood volume are
      recorded in sudden infant death syndrome and in infants living at low barometric
      pressures (high altitude). Low barometric pressure leads to chronic alveolar
      hypoxia (1,2). There is diversion and loss of body-fluid under conditions of
      microgravity (near-weightlessness) encountered in human space-travel and
      prolonged bedrest (3). The condition mimics shock and oligemia (4,5). The human
      neonate has underdeveloped postural mechanisms and low muscle-power. A
      transformation begins at about two months of age, which enables the human infant
      to adapt to the extrauterine environment (6). The neonate resembles the space
      traveller who, in a near-weightlessness antigravity environment, develops
      baroreceptor incompetence, visceral and venous congestion and oliguria. The low
      birthweight infant displays many of the disorders of the space traveller, viz.
      poor circulation, high blood-glucose, insulin resistance, weak muscles, slow gut
      absorption and bone demineralization (7-10). These conditions are virtually
      identical with the internal adjustments the body makes on lying down (negative
      gravity or near-weightlessness). We discuss the similarities of sudden infant
      death syndrome to low barometric pressure environment, orthostatic intolerance,
      the Pickwickian syndrome and X disease.

PMID- 8733170
TI  - Can we find a solution to the human immunodeficiency virus/acquired immune
      deficiency syndrome controversy? Is acquired immune deficiency syndrome the
      consequence of continuous excessive stressing of the body?
AB  - The time of re-evaluation of the role of human immunodeficiency viruses in the
      pathogenesis of acquired immune deficiency syndrome has now come, now that
      methods are available for the direct detection of human immunodeficiency viruses
      and for the detection of cellular anti-human immunodeficiency virus immune
      reactions. It has been shown that human immunodeficiency virus infections are
      common among anti-human immunodeficiency virus antibody negative high-risk
      individuals. The disease is brought under control by cellular immune reactions
      and the anti-human immunodeficiency virus antibody test remains negative. Apart
      from proof that infection with human immunodeficiency viruses has occurred, a
      positive result in an anti-human immunodeficiency virus-antibody test is also an
      indication of an independent immunosuppression state. According to the definition
      of the Centers of Disease Control classical acquired immune deficiency syndrome
      is the consequence of infection with human immunodeficiency virus in association
      with continuous excessive stress, such as observed in the known risk groups. At
      the center of the pathogenetic process is hypercortisolism-determined damage of T
      lymphocytes, in which insufficiency of thymus is prominent. For this reason, in
      our view, there are indications for shifting efforts from the prophylaxis of
      infection with human immunodeficiency viruses to the prophylaxis of acquired
      immune deficiency syndrome by reducing stress factors.

PMID- 8733171
TI  - A decreased incidence of neuroblastomas in Down's syndrome and overproduction of
      S-100 b protein.
AB  - Neuroblastoma, one of the most frequent solid tumors found in childhood, is very
      rare in Down's syndrome subjects. This lack could possibly be due to
      overproduction of S-100 b protein for the following reasons: 1) the gene coding
      for S-100 b protein is situated on chromosome 21, and the protein is overproduced
      via a gene dosage effect; 2) S-100 b protein is found in glial cells and Schwann
      cells of the central and peripheral nervous system and has been shown to have a
      differentiating effect on normal neural cells; 3) neuroblastomas with a stroma
      rich in S-100 protein have a good prognosis. Preliminary studies demonstrated an
      inhibition of growth of two human neuroblastoma cell lines in the presence of S
      100 b protein compared to controls. It is postulated that S-100 b protein may
      inhibit the development of neuroblastomas in Down's syndrome either antenatally,
      or after birth and may be a therapeutic agent against neuroblastoma.

PMID- 8733173
TI  - The induction of counter-interactions in tumor cells as a basis for the
      development of a therapy.
AB  - A tumor cell in a stringent situation is under the influence of two, opposite
      vectorial 'forces'. Resulting from the stringent situation, one of these 'forces'
      acts as an inhibitor of the synthesis process, whilst the perpetuation of the
      genetic induction of synthesis processes in the nucleus causes the second 'force'
      to act in the opposite manner. The influence of these 'forces' results in the
      formation of a counter interaction which leads to a 'breaking away' or decoupling
      of interdependent functions which are tuned to each other. This could be
      characterized as an apospasis and leads to irreversible cell-damage. If there is
      no decoupling, then there is a differentiation, or loss of the self-renewing
      capacity. Due to the fact that the counter interaction is inducible in tumor
      cells with proliferation activities as well as in tumor cells without
      proliferation activities, cells in both the growth and non-growth fraction can be
      attacked.

PMID- 8733172
TI  - Fish oil and other nutritional adjuvants for treatment of congestive heart
      failure.
AB  - Published clinical research, as well as various theoretical considerations,
      suggest that supplemental intakes of the 'metavitamins' taurine, coenzyme Q10,
      and L-carnitine, as well as of the minerals magnesium, potassium, and chromium,
      may be of therapeutic benefit in congestive heart failure. High intakes of fish
      oil may likewise be beneficial in this syndrome. Fish oil may decrease cardiac
      afterload by an antivasopressor action and by reducing blood viscosity, may
      reduce arrhythmic risk despite supporting the heart's beta-adrenergic
      responsiveness, may decrease fibrotic cardiac remodeling by impeding the action
      of angiotensin II and, in patients with coronary disease, may reduce the risk of
      atherothrombotic ischemic complications. Since the measures recommended here are
      nutritional and carry little if any toxic risk, there is no reason why their
      joint application should not be studied as a comprehensive nutritional therapy
      for congestive heart failure.

PMID- 8733174
TI  - High blood pressure, oxygen radicals and antioxidants: etiological relationships.
AB  - This hypothesis proposes that high blood pressure is a pathological state
      associated with a loss of the balance between pro-oxidation and antioxidation,
      energy depletion, and accelerated aging in the target organs, such as heart,
      kidney and brain. Different nutritional, environmental, pharmacological factors
      and/or associated pathologies (diabetes, arteriosclerosis, cancer, alcoholism,
      etc.) and/or genetic components, can induce high blood pressure by breaking the
      redox equilibrium in the affected organs. Additional evidence, such as increase
      of oxidative damage, fibrogenesis, inhibition of the cardiocytic sodium-potassium
      pump, and heart hypertrophy, supports this hypothesis. These facts are analysed
      in the present paper, showing that they could contribute to the development of
      high blood pressure and associated pathologies by oxidative mechanisms.

PMID- 8733175
TI  - Ban on beef exports: Commission awaits specific proposals from Britain.

PMID- 8733176
TI  - Lords consider the origins--and the future--of the beef crisis.

PMID- 8733177
TI  - The incidence of bovine spongiform encephalopathy in the progeny of affected
      sires and dams.
AB  - Case control study techniques were used to compare the incidence of bovine
      spongiform encephalopathy (BSE) in the progeny of two affected sires and 110
      affected dams with the incidence of BSE in the progeny of animals known to be
      unaffected at the last record. All the progeny were born before the ban on
      ruminant-derived protein in feedstuffs issued in July 1988. The results provide
      little, if any, evidence of differences between the incidence in the progeny of
      the affected animals and the incidence in the progeny of the presumed unaffected
      animals. Data from five herds were used in a logistic regression analysis to
      study the effects of the disease status of the dam and the age of the dam at the
      birth of the calf on the incidence of BSE. The disease status of the dam did not
      significantly affect the disease status of its progeny, after allowance had been
      made for the effects of herd, year and the age at last record of the progeny. The
      difficulty of establishing maternal transmission if a high proportion of the dams
      are incubating the disease and transmission can occur early in the incubation
      period is discussed.

PMID- 8733178
TI  - Comparison of two selective media for the isolation of Brucella melitensis from
      naturally infected sheep and goats.
AB  - The efficacy of two selective media for the isolation of Brucella melitensis from
      naturally infected sheep and goats was compared. Two hundred and eighty sheep and
      60 goats belonging to B melitensis-infected flocks were slaughtered and samples
      of milk (when available) and seven tissues were taken from each animal for
      bacteriological analyses. A modified Thayer-Martin's medium was more sensitive
      than Farrell's medium; by the combined use of both media 142 infected sheep and
      40 infected goats were detected, and 486 of the samples from the sheep and 179 of
      the samples from the goats were found to be infected.

PMID- 8733179
TI  - Detection of Salmonella enteritidis in eggs by the polymerase chain reaction.
AB  - A polymerase chain reaction (PCR) for the specific detection of the gene
      sequence, sefA, encoded by all isolates of Salmonella enteritidis, was developed.
      The PCR could detect as few as four S enteritidis washed bacterial cells but egg
      contents inhibited the PCR. Eggs spiked with 50 S enteritidis bacterial cells
      were homogenised, inoculated into buffered peptone water and grown at 37 degrees
      C for 16 hours, when the PCR was successful. A positive internal control was
      developed to differentiate between true and false negative PCR results for the
      detection of S enteritidis. In a limited trial of the egg handling procedures and
      the PCR, one of 250 chickens' eggs from retail outlets was found to be
      contaminated with S enteritidis.

PMID- 8733180
TI  - Bovine papillomavirus type 4 DNA isolated from a skin lesion in a steer.
AB  - A lesion on the head of a steer, defined histologically as an epithelial
      papilloma, yielded DNA which did not hybridise with any of the bovine
      papillomavirus DNAs usually associated with the formation of skin lesions. DNA
      from the lesion did hybridise with DNA from bovine papillomavirus 4, even under
      stringent conditions, and contained a sequence that could be amplified by
      polymerase chain reaction with primers specific for that virus. Bovine
      papillomavirus 4 had previously been isolated only from lesions of the upper
      alimentary canal.

PMID- 8733181
TI  - Isolation and characterisation of an avian paramyxovirus type 1 from turkeys in
      Northern Ireland.

PMID- 8733182
TI  - In vitro cytotoxicity of sera of paralysed ostriches showing serological
      positivity for Borna disease virus.

PMID- 8733183
TI  - Diagnosis and prevalence of neosporosis in cattle in Northern Ireland.

PMID- 8733184
TI  - The BSE crisis.

PMID- 8733185
TI  - The BSE crisis.

PMID- 8733186
TI  - Rickettsia-like organism in farmed salmon.

PMID- 8733187
TI  - Low bulk milk SCC and toxic mastitis.

PMID- 8733189
TI  - Teat licking in dairy cattle.

PMID- 8733191
TI  - Women's health: dimensions and differentials.
AB  - This paper is concerned with the social patterning of ill-health amongst women in
      Britain. It uses the various health measures available in the Health and
      Lifestyle Survey (self-assessed health, disease/disability, illness, psycho
      social well-being and fitness) to explore whether there are particular aspects of
      health systematically associated with social advantage and disadvantage, as
      measured by current or last occupation, employment status, household composition
      and household income. Among women aged 18-59, after controlling for age, number
      of psychological symptoms experienced in the past month showed the greatest
      social variation. Number of physical illness symptoms in the last month showed
      the least. Lone mothers with dependent children were found to have particularly
      poor psycho-social health, although this was confined to those in full-time
      employment. The presence of a long-standing disease/disability proved useful as a
      control for the influence of health selection in to and out of both employment
      and motherhood.

PMID- 8733192
TI  - Psychosocial work environment in human service organizations: a conceptual
      analysis and development of the demand-control model.
AB  - This paper concerns two models that were introduced in two different research
      domains during the 1970's. The first model regards human service organizations
      (HSO) as a specific type of organization. The second model, the demand-control
      model (DC model), concerns the joint effects of job demands and job control on
      worker health. In the HSO model, there are analyses of the content of jobs,
      considering the specific characteristics of HSOs, but little is said about the
      health effects of such work. Those effects stand in focus in the demand-control
      model. The aim of this paper is to analyze the relevance of the DC model for
      human service organizations. The paper argues that the object of human service
      work-the client relation-makes a difference for demand and control in the job.
      Demand is analyzed into work load, emotional demands and role conflict. Control
      is divided into administrative control, outcome control, choice of skills,
      closeness of supervision, control within and over a situation and ideological
      control. The conclusion is that in applications on HSOs, the basic concepts of
      the DC model must be developed.

PMID- 8733193
TI  - The diet-heart disease hypothesis: a response to Atrens.
AB  - In a recent examination of the main tenets of the widely accepted diet-heart
      disease hypothesis, Atrens concluded that the evidence to date is not sufficient
      to support the hypothesis. Reviewing Atrens' critique highlights both strengths
      and limitations in his case against the role of dietary lipids and cholesterol in
      coronary heart disease mortality. Research on the following hypothesized
      relationships is discussed in light of the objections raised by Atrens: the
      relationships between fat intake and heart disease mortality; dietary fat and
      serum cholesterol; serum cholesterol and atherosclerosis; atherosclerosis and
      heart disease death; and serum cholesterol and heart disease death. The
      inconsistency of the findings suggests that definitive answers regarding the diet
      heart disease hypothesis are premature and that the polarized positions of
      acceptance vs rejection of the hypothesis fail to account for the full range of
      results.

PMID- 8733194
TI  - Dynamics of participation in a community health project.
AB  - Although the term 'participation' is widely used in discussing community
      development strategies, there has been relatively little said about the
      characteristics of 'participatory relationships', i.e. the interactions between
      community developers and those who stand to benefit from community development
      initiatives. There is seen to be a need for case studies which attempt to
      understand the relational and communicative processes involved in participatory
      development. The paper presents an analysis of the participatory dynamics of a
      community health development project. The principal source of data is interviews
      conducted with thirteen selected participants in the project. Analysis of
      interview data using a structured hermeneutic method led to a description of the
      meaning of participation for each of the participants interviewed. Further
      interpretation led to the identification of a number of modes of participation in
      the project as a whole. For each mode of participation descriptions were
      developed of how it was perceived by others not participating from that mode. An
      attempt was made to understand the dynamics of the project in terms of the
      relationship between the different modes of participation and in terms of the
      discrepancies between how participants saw themselves and how others saw them.
      Finally, these problems were discussed at a general theoretical level and
      suggestions were made about how such problems might be alleviated.

PMID- 8733195
TI  - Doctors and the health industry: a case study of transcutaneous oxygen monitoring
      in neonatal intensive care.
AB  - This case study presents an industry perspective on medical innovation.
      Introduced as a scientific breakthrough in the late 1970s, transcutaneous oxygen
      monitoring was rapidly adopted for routine use in neonatal intensive care. But
      plagued by technical problems, it was within a decade being replaced by pulse
      oximetry, a still more recent technology. Its use in efforts to prevent
      retinopathy of prematurity, an eye disease of preterm newborns often leading to
      blindness, proved disappointing. The project included interviews with executives
      and design engineers of companies marketing the device, with investigators who
      had pioneered the technology, and with senior practicing neonatologists. The
      findings, reflecting complexity and uncertainty, are relevant to issues
      concerning health care in the United States and other developed nations. They
      centre on the key role and ultimate responsibility of the medical profession,
      with a need for greater attention to the scientific training of health care
      workers, as perceived by members of the medical device industry. The views of
      senior investigators are integrated into the picture, with discussion of major
      challenges faced by the medical community.

PMID- 8733196
TI  - A cost-benefit analysis of voluntary routine HIV-antibody testing for hospital
      patients.
AB  - The objectives of this paper are threefold: first, to develop a taxonomy of
      potential benefits from voluntary, routine HIV-antibody testing of hospital
      patients; second, to inform attending healthcare workers, hospital patients and
      policy makers of the potential benefits from such testing; and third, to make
      inferences about whether such testing is warranted by a cost-benefit criterion.
      Benefits stemming from information about a patient's HIV serostatus accrue to:
      (1) healthcare workers if extra precautions reduce their HIV-exposure rate; (2)
      the patient if knowledge of HIV serostatus allows life-extending prophylactic
      treatment to be initiated; and (3) the patient's sex partners if the patient is
      less likely to transmit HIV after undergoing HIV testing. Using recent estimates
      on the value of life, hospital-specific HIV-prevalence rates, the effectiveness
      of prophylactic treatment, rates of HIV exposure and conversion by healthcare
      workers, and reduction in high-risk sexual behaviors by seropositive patients, we
      estimate the benefits of testing as the value of statistical life saved. The
      opportunity cost of HIV testing is calculated as the reported cost of a standard
      HIV-test protocol with pre- and post-test counseling. Information about a
      patient's HIV serostatus provides small expected benefits to healthcare workers
      ($3.34) because the risk of HIV transmission is small; benefits to attending
      healthcare workers are insufficient to warrant routine HIV testing on a stand
      alone basis even in high HIV-prevalence hospitals. However, an HIV-seropositive
      test result provides large expected benefits to the patient ($11,202) and to the
      patient's sex partners ($5271). Adding these nonrivalrous benefits, we find that
      routine, voluntary HIV-testing of hospital patients passes a cost-benefit test
      even in low HIV-prevalence hospitals. Four major qualifications of the cost
      benefit analysis should be considered. (1) The benefits to some parties can only
      be achieved if the patient's serostatus is disclosed to them. (2) The net
      benefits may be negative if HIV-testing induces riskier behavior. (3) The
      analysis does not incorporate the significant potential for third-parties
      (employers, insurers, healthcare workers) to use the test to impose costs on HIV
      seropositive patients. (4) The sample of inpatients choosing voluntary HIV
      testing may not be representative of the overall hospital population. These
      unmeasured factors suggest that policymakers should exercise caution in
      implementing a voluntary HIV-testing program.

PMID- 8733197
TI  - A regional comparison of socioeconomic and health indices in a Canadian province.
AB  - In most jurisdictions, information on socioeconomic attributes of geographic
      areas is readily available. As well, limited measures of health, such as
      mortality rates or indicators derived from health service use, are also routinely
      collected for geographically defined populations. In this paper we present a
      methodology for selecting and combining measures of area socioeconomic
      characteristics to produce a composite index which is relevant for health-related
      research. The performance of this composite index in this setting was consistent
      with deprivation indices developed in the United Kingdom, and showed strong
      associations with measures of population health status and health service
      utilization.

PMID- 8733198
TI  - Social vs biological: theories on the transmission of AIDS in Africa.
AB  - There are fundamental differences in the epidemiological patterns of AIDS in
      Africa and the United States. A number of theories have been advanced to explain
      these differences. These theories may be divided into two basic approaches,
      theories based upon biological explanations and theories based upon social
      explanations. Biological based theories include a socio-biological explanation
      and a natural history explanation. The social theories may be divided into three
      theories which are historical/materialist in their explanation of AIDS in Africa
      and one theory which is primarily idealist and cultural in its explanation. The
      present article critically examines these biological and social theories. It
      argues that the biological theories lack scientific support, lack sufficient
      evidential support, have an inequality of cause and effect, and fail to integrate
      the micro/macro. This article argues that the social theories also have some
      major difficulties including, in some cases, a failure to integrate the
      micro/macro and a lack of adequate or sufficient causation to produce the massive
      epidemic of AIDS in Africa. There are difficulties with the quality of evidence
      and support for the social theories and more research needs to be conducted,
      particularly in the form of retrospective studies, to determine the validity of
      various social theories which attempt to explain the epidemiological patterns of
      the AIDS epidemic in Africa.

PMID- 8733199
TI  - The risky and protective motorcycling opinions and behaviours of young on-road
      motorcyclists in New Zealand.
AB  - This research documented the frequency of protective and risky motorcycling
      opinions and behaviours and investigated whether these opinions and behaviours
      were more frequently expressed by licensed than unlicensed riders and by riders
      with high rather than low exposure to motorcycling. Areas where there was scope
      for improvement were identified to help guide the promotion of protective
      strategies. As part of a broader study of a birth cohort, 217 18 year old
      motorcyclists were administered a motorcycling computer questionnaire. Evidence
      of positive protective opinions was found, but there was considerable scope for
      behavioural improvements. While 92% had worn a helmet, optimal protection was
      reported less frequently for other body areas: most often for the feet (54%),
      hands (47%) and upper body (35%) and least often for the legs (8%). Most (87%)
      riders considered conspicuity increased safety, 68% favoured mandatory day-time
      headlight use, and 66% used dipped headlights in day-time. While 55% favoured
      mandatory wearing of high-visibility clothing, only 15% of day-time and 20% of
      night-time riders reported doing this. During the past month, 16% had driven
      within two hours of drinking alcohol and 6% when too tired to be fully in
      control. Overall, 22% had been penalized for a motorcycle driving offence, most
      often speeding. While 46% said they agreed with the Graduated Driver Licensing
      System (GDLS), most licensed under that system reported breaking licence
      conditions and most were not apprehended. Licensed motorcyclists were
      significantly more likely than the unlicensed to favour mandatory day-time
      headlight usage, report using dipped headlights in day-time, and wear better
      protection for the head, upper body and hands, but were also more likely to
      report drinking and driving and traffic convictions--probably because of their
      greater exposure. Other, non-significant, results were in the same direction,
      except that fewer licensed than unlicensed riders were in favour of mandatory
      high visibility clothing or the GDLS. A similar pattern of more protective
      attitudes and behaviours was found for high rather than low exposure riders,
      though it was generally weaker, and high exposure was associated with drinking
      and driving, driving while tired and traffic convictions. The issues of
      representativeness and reliability are discussed and some implications for public
      policies towards motorcycling by young people are considered. Further research is
      recommended in order to determine which are the best predictors of motorcycling
      opinions and behaviours: personal characteristics, the formal training associated
      with licensure, or exposure to motorcycling.

PMID- 8733200
TI  - Predictors of non-urgent utilization of hospital emergency services in Kuwait.
AB  - Utilization of the emergency rooms (ERs) in Kuwait has increased considerably
      during the last decade. Such an increase is a concern for health planners because
      of the burden on ER services, lack of continuous service provided by the ER and
      the higher cost of such services. Based on a study of 2011 patients attending the
      medical ERs in the six government hospitals in early 1993, the predictors of non
      urgent utilization were analyzed. Patients were asked about their reasons for
      visiting the ER rather than the primary health care (PHC) centre. Both patients
      and doctors were asked to rate the urgency of the visit. According to the
      doctors' judgement, 61% of the visits were for non-urgent problems that did not
      require emergency care, while 23% of the patients viewed their visits to be non
      urgent. Multiple logistic regression analysis indicated that perceived urgency of
      the visit was the most important predictor of a non-urgent visit to the ER, after
      controlling for several predisposing and enabling factors. Patients who perceived
      their visit to the ER to be non-urgent were about four times more likely to visit
      the ER for a non-urgent condition as judged by the doctor. The level of education
      had a significant, positive effect on non-urgent utilization among both Kuwaiti
      nationals and expatriates. Several factors may explain the above finding.
      Employment of educated persons in the hospital was one route through which
      education facilitated ER use. It is also likely that educated persons had more
      influential contacts or wasta in the hospital. Also, the less educated might have
      delayed seeking care while the educated consulted for non-urgent reasons as soon
      as they noticed the symptoms. Like education, the level of non-urgent utilization
      was higher among Kuwaiti nationals with higher incomes. Thus, a higher social
      class seems to facilitate ER use for non-urgent reasons. Among the non-Kuwaitis,
      lack of registration at the PHC centre was a significant reason for non-urgent
      use of the ER. It is recommended that hurdles in the utilization of PHC
      facilities should be removed. Registration of non-Kuwaitis at the PHC must be
      improved, and referrals to the PHC back from the ER should be instituted to
      ensure the necessary follow-up care.

PMID- 8733201
TI  - Notes on the socio-economic and cultural factors influencing the transmission of
      HIV in Botswana.
AB  - Botswana currently has one of the highest recorded incidences of HIV infection in
      Africa although AIDS was only first publicly recognized in 1985. By this time
      other countries in the region such as Malawi, Zambia and Uganda were already
      showing signs of epidemic levels of HIV. The rapid transmission of HIV in
      Botswana has been due to three main factors; the position of women in society,
      particularly their lack of power in negotiating sexual relationships: cultural
      attitudes to fertility; and social migration patterns. These three factors along
      with other, arguably more minor, ones have been shaped and mediated within the
      specific context of Botswana's rapid socio-economic development and cultural
      milieu. This has resulted in a constellation of factors unique to Botswana which
      accounts for the current high seroprevalence rate in the country.

PMID- 8733202
TI  - Prevalence of dementia in Japan.

PMID- 8733203
TI  - Are life events related to the onset of breast cancer.

PMID- 8733204
TI  - Patterns of DSM-III-R alcohol dependence symptom progression in a general
      population survey.
AB  - Age of onset reports obtained retrospectively for each symptom of DSM-III-R
      alcohol dependence (AD) are used to study patterns of lifetime symptom
      progression in a large general-population survey of people in the United States.
      It is shown that symptom progression among a substantial majority of respondents
      can be summarized as movement across three clusters. Cluster A is defined by
      symptoms of role impairment/hazardous use (A4), use despite social, psychological
      or physical problems (A6), and drinking larger amounts or over a longer period of
      time than intended (A1). Cluster B is defined by tolerance (A7) and impaired
      control (A2, A3). Cluster C is defined by withdrawal (A8, A9) and giving up
      activities in order to drink (A5). Clusters are shown to follow a time sequence,
      with at least one symptom in Cluster A usually occurring first, followed by
      symptoms in Clusters B and C. In all, 83.4% of the symptom cluster transitions
      estimated from retrospective age of onset reports are consistent with this
      progression. Progression to AD is differentially predicted by symptom profiles
      reported at the age of first symptom onset, with persons reporting Cluster C
      symptoms most likely to progress subsequently to AD. Furthermore, profiles of AD
      defined by the highest symptom cluster present at AD onset are differentially
      predicted by prior personal and parental histories of psychopathology and, among
      men, are predictive of diagnosis persistence.

PMID- 8733205
TI  - The prophylaxis of depressive episodes in recurrent depression following
      discontinuation of drug therapy: integrating psychological and biological
      factors.
AB  - Models of long-term treatment in recurrent unipolar illness ideally should
      integrate both psychological and biological factors. In earlier reports we noted
      that high treatment specificity (i.e. good-quality maintenance interpersonal
      psychotherapy) and high delta sleep ratio were each associated with significantly
      increased wellness intervals in the absence of pharmacotherapy among patients
      with recurrent unipolar depression. To determine how these specific factors when
      taken together are related to length of survival time, we examined the concurrent
      effects of treatment specificity and delta sleep ratio on wellness intervals
      using survival analysis. We found significant effects of both treatment
      specificity and delta ratio on survival time. Seventy-three per cent of the
      patients in the high treatment specificity/high delta ratio group survived the 3
      year trial, while 44% of the patients in the low delta ratio but high treatment
      specificity group survived. None of those rated low on both variables survived.
      We also found an effect for individual clinicians on treatment specificity and
      survival time and noted that the prophylactic effect of treatment specificity was
      maintained even within subsets of therapists grouped by their patients' survival
      times. Secondary analyses revealed an effect of patient attitudes on treatment
      specificity and survival time, although, when taken together, treatment
      specificity was the only variable remaining significantly associated with
      outcome. We conclude that patients remain well the longest when pre-treatment
      delta sleep parameters more closely approximate those of non-depressed
      individuals and when monthly psychotherapy is of higher quality. The key finding
      is that high specificity is of significant prophylactic benefit even for patients
      with a biological vulnerability for recurrence. We also conclude that in addition
      to therapists, patient expectancies contribute to treatment specificity, and high
      treatment specificity is, in turn, reflected in longer times to recurrence.

PMID- 8733206
TI  - The Inventory of Depressive Symptomatology (IDS): psychometric properties.
AB  - The psychometric properties of the 28- and 30-item versions of the Inventory of
      Depressive Symptomatology, Clinician-Rated (IDS-C) and Self-Report (IDS-SR) are
      reported in a total of 434 (28-item) and 337 (30-item) adult out-patients with
      current major depressive disorder and 118 adult euthymic subjects (15 remitted
      depressed and 103 normal controls). Cronbach's alpha ranged from 0.92 to 0.94 for
      the total sample and from 0.76 to 0.82 for those with current depression. Item
      total correlations, as well as several tests of concurrent and discriminant
      validity are reported. Factor analysis revealed three dimensions (cognitive/mood,
      anxiety/arousal and vegetative) for each scale. Analysis of sensitivity to change
      in symptom severity in an open-label trial of fluoxetine (N = 58) showed that the
      IDS-C and IDS-SR were highly related to the 17-item Hamilton Rating Scale for
      Depression. Given the more complete item coverage, satisfactory psychometric
      properties, and high correlations with the above standard ratings, the 30-item
      IDS-C and IDS-SR can be used to evaluate depressive symptom severity. The
      availability of similar item content for clinician-rated and self-reported
      versions allows more direct evaluations of these two perspectives.

PMID- 8733207
TI  - The treatment of common mental disorders by a community team based in primary
      care: a cost-effectiveness study.
AB  - Thirty patients suffering from new episodes of depression or anxiety disorders
      seen by a hospital-based psychiatric service were matched for severity of illness
      with 30 patients seen by a community mental health team based upon primary care.
      These patients were drawn from a total of 108 such patients seen in the community
      and 57 seen by the hospital service. Clinical and social outcomes were similar in
      both groups, and neither was clearly superior in terms of quality of clinical
      information recorded. However, patients treated in the community were seen more
      quickly, had more continuity of care and were more satisfied with the service.
      Health services costs were less for those patients treated in the community,
      because patients were less likely to be admitted. With one atypical patient
      excluded, treatment by the community team is more cost effective. The greater
      number of patients seen by the primary-care-based service means that there is no
      overall cost saving to the NHS.

PMID- 8733208
TI  - Psychological distress among recent immigrants from the former Soviet Union to
      Israel, I. Correlates of level of distress.
AB  - In most migrations some selection takes place either by the absorbing country
      and/or the individuals who emigrate. Israel has an open-door policy for
      immigrants and the recent large wave of immigrants from the former Soviet Union
      was made up of entire families rather than individuals. This provided an
      opportunity to examine the issue of migration and psychological distress more
      directly. A nationwide sample of 600 immigrants who arrived during the preceding
      year were interviewed in December 1990. Their psychological distress was measured
      by the PERI Demoralization questionnaire. For both genders, the mean
      demoralization score of the immigrant sample was found to be significantly higher
      than that reported for the Israeli-born population (after controlling for
      education). The factors that were found to be correlated with the level of
      distress were mostly individual characteristics of the immigrants (e.g.
      profession, religiousness, former residence in the Chernobyl region, previous
      contact with the health profession because of psychological problems). Increased
      distress was also significantly related to perceived lack of social support in
      Israel, which may in fact be partly determined by personality traits.

PMID- 8733209
TI  - Psychological distress among recent immigrants from the former Soviet Union to
      Israel, II. The effects of the Gulf War.
AB  - The psychological effects of the Gulf War were studied on a group of Israeli
      civilians particularly at risk, viz. recent immigrants from the former Soviet
      Union. A quasi-experimental design was used. A sample of immigrants who had
      already been screened for psychological distress just before the war were
      reassessed after the war with the same instrument (PERI demoralization
      questionnaire). Various parameters related to the war period were also assessed.
      Psychological symptoms during the war were significantly associated with pre-war
      level of distress and with actual physical harm from the missiles, but not with
      exposure to danger (proximity of residence to areas hit by missiles). Correlates
      of behaviour in the face of life-threatening danger during the war (change of
      residence and help-seeking behaviour) were also identified. Overall the level of
      post-war psychological distress was not found to be higher than pre-war levels.
      This was explained by the immigrants' feelings of shared fate, belonging and
      sense of cohesion, which characterize the general Israeli population during war
      time.

PMID- 8733210
TI  - Factors affecting the success of community placement: the TAPS project 26.
AB  - Long-stay patients who were discharged from Friern and Claybury hospitals during
      the 6-year period between September 1985 and August 1991 were followed up for at
      least 1 year and the details of all readmissions were recorded. Of the 615
      hospital leavers, some 178 (29%) were readmitted at some time during the follow
      up period. A proportional hazards regression analysis revealed a number of
      independent baseline factors which affect the risk of readmission at any time
      during the follow-up period. Younger patients were more at risk of readmission
      than were older patients and 'new' long-stay patients had a greater risk than
      baseline patients. Risk was also greater in patients who had a larger number of
      pre-discharge admissions, a higher abnormal behaviour score (PSE BSO) or a
      diagnosis of manic psychosis. An ordinal logistic regression analysis revealed
      that these same five factors tended to increase the actual number of readmission
      episodes. The proportion of post-discharge time spent in hospital among the
      readmitted patients was found to be greater for males, new long-stay patients and
      for patients with a higher number of positive social behaviour symptoms (SBSPOS
      score).

PMID- 8733211
TI  - Exploring 'theory of mind' in people with schizophrenia.
AB  - Mentalizing ability was studied in 46 symptomatic schizophrenic patients and 44
      non-symptomatic controls. Subjects heard six stories and simultaneously were
      shown simple cartoon pictures depicting the action sequencing occurring in the
      stories. All the stories involved false belief or deception, so that it was
      necessary to infer the mental states of the characters in order to understand
      their behaviour. After each story, subjects were asked one memory/reality
      question (concerning an event in the story) and one question that depended on the
      ability to infer the mental state of one of the characters. Patients with
      paranoid delusions were impaired on the questions concerning mental states.
      Patients with behavioural signs (i.e. negative features or incoherence) were also
      impaired on the mental state questions, but this difficulty was associated with
      memory impairments. Patients with symptoms of passivity (e.g. delusions of
      control) and patients in remission did not differ from normal controls. These
      results are consistent with the hypothesis that certain of the positive symptoms
      of schizophrenia reflect an impairment in the ability to infer the mental states
      of others.

PMID- 8733212
TI  - The construction and characteristics of an instrument to measure personal
      hopefulness.
AB  - This paper describes the construction, refinement and implementation of a self
      administered measure of personal hopefulness, the Hunter Opinions and Personal
      Expectations Scale (HOPES). Initial state and trait versions of the HOPES
      instrument were utilized in three separate studies, comprising a medical student
      sample (N = 211), an adolescent male sample (N = 280) and a psychiatric hospital
      staff sample (N = 318). A revised 20-item, two factor, trait version of the scale
      was then utilized in a prospective, longitudinal investigation (N = 753) of the
      psychosocial sequelae of the earthquake which struck Newcastle (Australia) in
      December, 1989. Data from all four studies provide strong support for the HOPES
      instrument's construct, concurrent and predictive validity. Global personal
      hopefulness (GPH) was shown to be an enduring characteristic of individuals, with
      a test-retest correlation of r = + 0.71 (over 64 weeks). The association between
      GPH and trait anxiety (r = -0.64) raised the possibility of redefining anxiety as
      hope under threat. The hope subscale (HS) and the despair subscale (DS) were
      moderately negatively correlated (r = -0.32), suggesting that hope and despair
      are not simply polar opposites. There were no gender differences in GPH scores,
      however, there were relatively clear age effects, with those aged 70 years and
      over reporting the lowest levels of personal hopefulness. GPH was negatively
      correlated with post-earthquake scores on the General Health Questionnaire (r = 
      0.33), the Impact of Event Scale (r = -0.33), the Beck Depression Inventory (r = 
      0.54) and the global symptom index from the SCL-90-R (r = -0.43). Overall, the
      contribution made by personal hopefulness to post-earthquake morbidity was equal
      to the contributions made by initial exposure to disruption and threat
      experiences.

PMID- 8733213
TI  - Increase of serum creatine phosphokinase in catatonia: an investigation in 32
      acute catatonic patients.
AB  - We investigated serum creatine phosphokinase (CPK) and associated parkinsonic
      (SEPS) and dyskinetic (AIMS) movements in 32 hospital admitted acute catatonic
      patients. Thirty-two (N = 24 without neuroleptics on admission) catatonic
      patients were compared with 32 non-catatonic dyskinetic psychiatric patients, 32
      non-catatonic non-dyskinetic psychiatric patients and 32 healthy controls. CPK
      was significantly higher (P = 0.015) in catatonics (mean 255.75, S.D. +/- 226.54)
      than in healthy controls (38.6, +/- 27.4) and non-catatonic non-dyskinetic
      psychiatric patients (57.1, +/- 120.8) whereas there was no significant
      difference between catatonics and non-catatonic dyskinetic psychiatric patients
      (453.4, +/- 128.5). There were significantly positive correlations between CPK
      and AIMS, as well as significantly negative correlations between CPK and SEPS, in
      all three groups. Our results suggest that increased serum CPK in catatonia may
      be related to occurrence of dyskinetic movements. Furthermore, we were able to
      distinguish a parkinsonic (low CPK, low AIMS, high SEPS) and a dyskinetic (high
      CPK, high AIMS, low SEPS) subtype in catatonia.

PMID- 8733214
TI  - A longitudinal study of factors predicting change in cognitive test scores over
      time, in an older hypertensive population.
AB  - This study aims to describe factors associated with cognitive decline among 2584
      subjects, aged 65-74, who were followed up for 54 months in the Medical Research
      Council Elderly Hypertension Trial (1982-1989). The subjects completed a
      cognitive test, the Paired Associate Learning Test (PALT), five times over this
      period. Decline on the PALT was associated with advanced age, male sex, rural
      residence, depression and low intelligence. These effects were modified by gender
      and level of pre-morbid intelligence. Advanced age, rural residence and number of
      cigarettes smoked daily were only associated with PALT decline among women of
      below median intelligence. The association between depression and PALT decline
      was only apparent in women of below median intelligence and men of above median
      intelligence. While these findings are consistent with other research into
      cognitive decline, they differ in some ways from reported risk factors for
      dementia, suggesting aetiological separateness. That women were more vulnerable
      than men to the effects of age and smoking raises the question of the impact on
      cognition of accelerated atherosclerosis after the menopause.

PMID- 8733215
TI  - Infant growth in the context of maternal eating disorders and maternal
      depression: a comparative study.
AB  - There is evidence of growth faltering in infants of mothers with eating
      disorders. The aim of the current study was to examine whether this is a specific
      relationship. Thus, the infants of mothers with eating disorders were compared
      with infants of mothers with post-natal depression and a large comparison group.
      This study also aimed to explore possible mechanisms whereby growth disturbance
      comes about. It was found that the infants of mothers with eating disorders were
      smaller, both in terms of weight for length and weight for age, than either
      comparison group infants or infants of mothers with post-natal depression. There
      was little evidence, however, that mothers with eating disorders preferred
      smaller children or were dissatisfied with their children's shape or that they
      misperceived their children's size. On the contrary these mothers seemed highly
      sensitive to their children's shape and, compared with the other two groups, were
      more likely to judge their children's size accurately. None of these maternal
      measures significantly predicted the child's growth. The mechanism whereby growth
      disturbance arises in the context of eating disorders does not appear to be by
      means of a direct extension of the maternal psychopathology to the infant.

PMID- 8733216
TI  - Transient and persistent hypochondriacal worry in primary care.
AB  - We present a 12-month prospective study of hypochondriacal worry in primary care.
      Data were obtained from 546 family medicine patients at the time of a physician
      visit for a new illness and again 1 year later. Patients were divided into four
      groups based on scores on the Illness Worry Scale: non-hypochondriacal (N = 460),
      transient hypochondriacal (N = 34); emerging hypochondriacal (N = 21); and
      persistent hypochondriacal (N = 31). Persistent patients had significantly more
      serious medical history but no more serious current illness than those low on
      illness worry. Patients with persistent illness worry were more likely than
      others to have a diagnosis of major depression or anxiety disorder, were more
      likely to believe that their most important significant other would pathologize
      new symptoms, yet were less likely to have been encouraged to see the doctor by
      them. Patients who became less worried over the year reported corresponding
      decreases in distress, attentiveness to bodily sensations, emotional
      vulnerability and pathological symptom attributions. We conclude that depressive
      or anxiety disorders, fears of emotional instability, pathological symptom
      attributional styles and interpersonal vulnerability provide the best prognostic
      evidence for enduring illness worry.

PMID- 8733217
TI  - Cognitive performance in tests sensitive to frontal lobe dysfunction in the
      elderly depressed.
AB  - The paper reports the profile of impairment across a variety of cognitive
      functions with special emphasis on tests sensitive to frontal lobe dysfunction,
      in 24 elderly depressed patients during and on recovery from mood disorder,
      compared with 15 age- and sex-matched controls. Traditional neuropsychological
      tests and a recently developed battery of computerized tests (CANTAB) were used.
      Impairments were found in the depressed group compared to controls and to
      themselves on recovery across all domains examined. The depressed group showed
      deficits on visuospatial recognition memory, attentional shifting at the extra
      dimensional shift stage and in measures of both processing and motor speed
      without impaired accuracy in a visual search task. Impairments were also found on
      a planning task with disproportionately increased numbers of moves needed for
      more difficult problems and evidence of both slowed motor response and increased
      processing time once the task was commenced. Performance on recovery improved
      across all tasks. Comparisons were made with the performance of patients
      suffering from dementia of the Alzheimer type (DAT) and Parkinson's disease on
      similar tests. Response latencies in test performance were found to correlate
      with the number of episodes of depression suffered and with ventricular size on
      CT scan, as measured by computerized planimetry. On recovery, residual depression
      scores correlated with latency of test performance and with ventricular brain
      ratio. The results, thus, show that depression in the elderly is associated with
      a significant degree of deficit on tests sensitive to frontostriatal dysfunction.
      Some of the deficits appear specific to depression and some do not remit
      following clinical recovery. However, these impairments have to be interpreted in
      the context of a broad profile of cognitive deficit.

PMID- 8733218
TI  - Aberrant interhemispheric alpha coherence on electroencephalography in
      schizophrenic patients during activation tasks.
AB  - Thirty schizophrenic patients (20 medicated, 10 off medication) were compared
      with 30 normal controls subjects matched for age, sex, handedness and
      intelligence. During the performance of a frontal activation task, normal
      subjects showed increased interhemispheric coherence between anterior brain
      regions. Schizophrenic patients did not show the same amount of bilateral
      anterior activation. During the performance of right hemisphere cognitive
      activation tasks, normal subjects and medicated schizophrenic patients showed
      significantly reduced bilateral interhemispheric coherence patterns, while the
      drug-free schizophrenic patients showed a trend towards this same pattern. It is
      suggested that these findings provide additional evidence for an aberrant
      functional organization of the brain in schizophrenia.

PMID- 8733219
TI  - Effects of positive and negative life events on time to depression onset: an
      analysis of additivity and timing.
AB  - While the relationship of life events to depression onset has occupied
      researchers for almost a quarter of a century, few studies have attempted to
      account for either the temporal patterning of events relative to episode onset,
      or, the effect of multiple events in a study period. In this report, we attempt
      to address the issues of timing of events, multiple events (both positive and
      negative) and multiple aspects (both positivity and negativity) of single events
      on latency time to depression onset, while simultaneously accounting for possible
      decay in the effects of events over time. We use the proportional hazards
      approach to model the effects of life events and consider modelling the change in
      impact of events with the passage of time. After interviewing 142 recurrent
      unipolar patients using the Life Events and Difficulties Schedule, we rated
      severity and positivity of life events reported during the 6-month period prior
      to onset. As we hypothesized, additional life events occurring after an initial
      provoking agent level event significantly alter the risk of illness onset.
      Additional severely threatening events decrease the time to onset, but positive
      events do not appear to delay onset. Interestingly, seemingly neutral events had
      a highly significant effect in shortening the time to onset. We note the many
      limitations imposed on the interpretation of these findings related to the
      selected group of subjects studied and encourage those who have more
      generalizable data to apply these methods of analysis.

PMID- 8733220
TI  - The development and validation of a predictive index for postpartum depression.
AB  - A sample of over 6000 women was recruited in the last trimester of pregnancy and
      administered a 40-item self-report questionnaire designed to detect the presence
      of factors that were likely to increase the risk of postpartum depression. The
      mental state of almost 5000 of these women was determined at around 6 to 8 weeks
      postpartum. By conducting a series of logistic regressions on two-thirds of this
      sample the original set of variables was reduced to a predictive index of 17
      items with weighted scores calculated for each. This index was then applied to
      the remaining one-third of the sample as a validating procedure and specificity
      and sensitivity calculated. The index offers a system for the prediction of
      postpartum depression that could be of use in both research and clinical
      practice.

PMID- 8733221
TI  - Defence style and behaviour therapy outcome in a specific phobia.
AB  - The Defense Style Questionnaire (DSQ) was administered to patients with a
      specific phobia (animal type; N = 54) and to control subjects (N = 29). Results
      indicated that specific phobia patients and non-phobic control subjects exhibit a
      similar pattern of defences. Also, the study investigated whether specific DSQ
      defence styles affect behaviour therapy outcome. It was found that an immature
      defence style, and especially the defence mechanism projection, was related to
      less favourable treatment results.

PMID- 8733222
TI  - Causal attributions about common somatic sensations among frequent general
      practice attenders.
AB  - The causal attributions that people make about bodily symptoms or sensations are
      likely to influence their decisions whether or not to consult a doctor. Previous
      research has supported the model that people tend initially to look for external
      or environmental explanations for bodily sensations (normalizing attributions)
      and only if this process fails do they search for attributions internal to
      themselves (somatic or psychological attributions). This study tested two
      hypotheses about frequent general practice attenders: (1) compared with others,
      they are more likely to make somatic attributions and less likely to make
      normalizing ones; and (2) given a bodily symptom together with a somatic
      explanation, frequent attenders will have greater difficulty than others in
      finding reasons why the given (pathological) explanation is untrue. The frequent
      attenders' group had themselves initiated an average of 12 general practice
      visits in the 12 months before assessment, while a control group of infrequent
      attenders had not made appointments to see their general practitioner for an
      average of 24 months. The results provide partial support for the hypotheses.
      Frequent attenders generated significantly fewer normalizing explanations for a
      series of common bodily sensations than the comparison group, although the two
      groups did not differ in their somatic attributions. Given a common bodily
      sensation and an accompanying pathological explanation, the frequent attenders
      were less able than the control group to generate reasons why the given
      explanation might be untrue. Some associations were found between these measures
      and anxiety.

PMID- 8733223
TI  - The vacuolating cytotoxin of Helicobacter pylori.
AB  - Helicobacter pylori, the causative agent of chronic superficial gastritis and
      duodenal ulcer disease in humans, produces a unique cytotoxin (VacA) that induces
      cytoplasmic vacuolation in eukaryotic cells. The structural organization and
      processing of the vacuolating cytotoxin are characteristic of a family of
      proteins exemplified by Neisseria gonorrhoeae IgA protease. Although only 50% of
      H. pylori isolates produce detectable cytotoxin activity in vitro, vacA
      homologues are present in virtually all isolates. Several families of vacA
      alleles have been identified, and there is a strong correlation between presence
      of specific vacA genotypes, cytotoxin activity, and peptic ulceration.
      Experiments in a mouse model of H. pylori-induced gastric damage indicate that
      the cytotoxin plays an important role in inducing gastric epithelial necrosis.

PMID- 8733224
TI  - Mycoplasma pneumoniae cytadherence: unravelling the tie that binds.
AB  - Mycoplasma pneumoniae is the leading cause of pneumonia in older children and
      young adults. Mycoplasma adherence to the respiratory epithelium (cytadherence)
      is required for colonization and pathogenesis. Although considered to be among
      the smallest and simplest known prokaryotes, this cell-wall-less bacterium
      possesses a highly differentiated terminal structure that is thought to be
      functional in mycoplasma cell division, gliding motility, and cytadherence.
      Mutant analysis has identified mycoplasma proteins associated with cytadherence,
      and revealed novel regulatory features. Ultrastructural and biochemical studies
      have established the subcellular location and interaction of key components,
      several of which are phosphorylated by ATP-dependent kinase(s) in a manner that
      is responsive to changing nutritional conditions. This review summarizes recent
      progress in defining the composition, organization and regulation of the
      attachment organelle. What emerges is a picture of M. pneumoniae cytadherence as
      a multifactorial process that extends well beyond adhesin-receptor recognition.

PMID- 8733225
TI  - Customized secretion chaperones in pathogenic bacteria.
AB  - Pathogenic yersiniae secrete about a dozen anti-host proteins, the Yops, by a
      pathway which does not involve cleavage of a classical signal peptide. The Yop
      secretory apparatus, called Ysc, for Yop secretion, is the archetype of type III
      secretion systems (which serve for the secretion of virulence proteins by several
      animal and plant pathogens) and is related to the flagellar assembly apparatus.
      The Yop secretion signal is N-terminal but has not been defined to date. Apart
      from the Ysc machinery, secretion of at least four Yops requires cytoplasmic
      proteins called Syc (for specific Yop chaperone). Each Syc protein binds to its
      cognate Yop. Unlike most cytoplasmic chaperones, these proteins do not have an
      ATP-binding domain, and are presumably devoid of ATPase activity. They share a
      few common properties: an acidic pl, a size in the range of 15-20 kDa, and a
      putative amphipathic alpha-helix in the C-terminal portion. They were recently
      shown to have counterparts in other pathogenic bacteria, where they appear to
      have a similar function.

PMID- 8733226
TI  - Molecular genetic bases of Salmonella entry into host cells.
AB  - Salmonella spp. can enter into non-phagocytic cells, a property that is essential
      for their pathogenicity. Recently, considerable progress has been made in the
      understanding of the molecular genetic bases of this process. It is now evident
      that Salmonella entry functions are largely encoded on a 35-40 kb region of the
      Salmonella chromosome located at centisome 63. The majority of the loci in this
      region encode components of a type III or contact-dependent secretion system
      homologous to those described in a variety of animal and plant-pathogenic
      bacteria as well as a number of proteins that require this system for their
      export to the extracellular environment. A somewhat unexpected finding has been
      the remarkable homology between the Salmonella and Shigella proteins that mediate
      the entry of these organisms into cultured epithelial cells.

PMID- 8733227
TI  - Transcriptional activator of phage phi 29 late promoter: mapping of residues
      involved in interaction with RNA polymerase and in DNA bending.
AB  - Phage phi 29 regulatory protein p4 activates transcription from the late A3
      promoter by stabilizing sigma A-RNA polymerase at the promoter as a closed
      complex. Activation requires interaction between both proteins. Protein p4 bends
      the DNA upon binding. We have performed a detailed mutagenesis study of the
      carboxyl end of the protein, which is involved in both transcription activation
      and DNA bending. The results indicate that Arg-120 is the most critical residue
      for activation, probably mediating the interaction with RNA polymerase. Several
      basic residues have been identified, including Arg-120, that contribute to
      maintenance of the DNA bending, probably via electrostatic interactions with the
      DNA backbone. The degree or stability of the induced bend apparently relies on
      the additive contribution of all basic residues of the carboxyl end of the
      protein. Therefore, the activation and DNA bending surfaces overlap, and Arg-120
      should interact with both DNA and RNA polymerase. As we show that protein p4 is a
      dimer in solution, and is bound to DNA as a tetramer, the results suggest a model
      in which two of the p4 subunits interact with the DNA, bending it, while the
      other two subunits remain accessible to interact with RNA polymerase.

PMID- 8733228
TI  - Organization of the origins of replication of the chromosomes of Mycobacterium
      smegmatis, Mycobacterium leprae and Mycobacterium tuberculosis and isolation of a
      functional origin from M. smegmatis.
AB  - The genus Mycobacterium is composed of species with widely differing growth rates
      ranging from approximately three hours in Mycobacterium smegmatis to two weeks in
      Mycobacterium leprae. As DNA replication is coupled to cell duplication, it may
      be regulated by common mechanisms. The chromosomal regions surrounding the
      origins of DNA replication from M. smegmatis, M. tuberculosis, and M. leprae have
      been sequenced, and show very few differences. The gene order, rnpA-rpmH-dnaA
      dnaN-recF-orf-gyrB-gyrA, is the same as in other Gram-positive organisms.
      Although the general organization in M. smegmatis is very similar to that of
      Streptomyces spp., a closely related genus, M. tuberculosis and M. leprae differ
      as they lack an open reading frame, between dnaN and recF, which is similar to
      the gnd gene of Escherichia coli. Within the three mycobacterial species, there
      is extensive sequence conservation in the intergenic regions flanking dnaA, but
      more variation from the consensus DnaA box sequence was seen than in other
      bacteria. By means of subcloning experiments, the putative chromosomal origin of
      replication of M. smegmatis, containing the dnaA-dnaN region, was shown to
      promote autonomous replication in M. smegmatis, unlike the corresponding regions
      from M. tuberculosis or M. leprae.

PMID- 8733229
TI  - Purification of recombinant Chlamydia trachomatis histone H1-like protein Hc2,
      and comparative functional analysis of Hc2 and Hc1.
AB  - The metabolically inactive developmental form of Chlamydia trachomatis, the
      elementary body, contains two very basic DNA-binding proteins with homology to
      eukaryotic histone H1. One of these, Hc1, is relatively well characterized and
      induces DNA condensation in vitro, whereas the other, Hc2, is functionally
      virtually uncharacterized. In this study we describe the purification of Hc2, and
      a detailed comparative functional analysis of Hc2 and Hc1 is presented. By gel
      shift assays and electron microscopy, marked differences in the nucleic acid
      binding properties of Hc2 and Hc1 were observed. Furthermore, Hc2 was found to
      strongly inhibit translation and transcription in vitro. Our results imply that
      DNA condensation is not the only function of Hc2.

PMID- 8733230
TI  - EspA, a protein secreted by enteropathogenic Escherichia coli, is required to
      induce signals in epithelial cells.
AB  - Enteropathogenic Escherichia coli (EPEC) is a leading cause of infant diarrhoea.
      EPEC mediates several effects on host epithelial cells, including activation of
      signal-transduction pathways, cytoskeletal rearrangement along with pedestal and
      attaching/effacing lesion formation. It has been previously shown that the EPEC
      eaeB (espB) gene encodes a secreted protein required for signal transduction and
      adherence, while eaeA encodes intimin, an EPEC membrane protein that mediates
      intimate adherence and contributes to focusing of cytoskeletal proteins beneath
      bacteria. DNA-sequence analysis of a region between eaeA and eaeB identified a
      predicted open reading frame (espA) that matched the amino-terminal sequence of a
      25 kDa EPEC secreted protein. A mutant with a non-polar insertion in espA does
      not secrete this protein, activate epithelial cell signal transduction or cause
      cytoskeletal rearrangement. These phenotypes were complemented by a cloned espA
      gene. The espA mutant is also defective for invasion. It is concluded that espA
      encodes an EPEC secreted protein that is necessary for activating epithelial
      signal transduction, intimate contact, and formation of attaching and effacing
      lesions, processes which are central to pathogenesis.

PMID- 8733231
TI  - A cluster of fourteen genes from enteropathogenic Escherichia coli is sufficient
      for the biogenesis of a type IV pilus.
AB  - Enteropathogenic Escherichia coli (EPEC) adhere to epithelial cells in
      microcolonies, a pattern termed localized adherence (LA). LA is dependent upon
      the presence of 50-70 MDa plasmids, termed EPEC adherence factor (EAF) plasmids.
      Expression of an EAF plasmid-encoded type IV fimbria, the bundle-forming pilus
      (BFP), is associated with the LA phenotype. TnphoA insertions in bfpA, the gene
      encoding the major structural subunit of the BFP, abolish LA. While bfpA::TnphoA
      mutants cannot be complemented for LA by plasmids carrying the bfpA gene alone in
      trans, this work shows that they can be complemented by plasmids carrying the
      bfpA gene, as well as approximately 10 kb of downstream sequence, suggesting that
      such mutations have polar effects on downstream genes. The identification and
      characterization of a cluster of 13 genes immediately downstream of bfpA are
      described. The introduction into a laboratory Escherichia coli strain of a
      plasmid containing these 14 bfp gene cluster genes, along with pJPN14, a plasmid
      containing another fragment derived from the EAF plasmid, confers LA ability and
      BFP biogenesis. However, when a mutation is introduced into the last gene of the
      bfp cluster, neither LA nor BFP biogenesis is conferred. This work also provides
      evidence to show that the fragment cloned in pJPN14 encodes a factor(s) which
      results in increased levels of the pilin protein. Finally, it is shown that
      expression of the 14 genes in the bfp cluster from an IPTG-inducible promoter, in
      the absence of pJPN14, is sufficient to reconstitute BFP biogenesis in a
      laboratory E. coli strain, but is insufficient for LA. This is the first report
      demonstrating the reconstitution of a type IV pilus in a laboratory E. coli
      strain with a defined set of genes. The BFP system should prove to be a useful
      model for studying the molecular mechanisms of type IV pilus biogenesis.

PMID- 8733232
TI  - Bacillus subtilis operon under the dual control of the general stress
      transcription factor sigma B and the sporulation transcription factor sigma H.
AB  - The sigma B transcription factor of Bacillus subtilis is activated in response to
      a variety of environmental stresses, including those imposed by entry into the
      stationary-growth phase, and by heat, salt or ethanol challenge to
      logarithmically growing cells. Although sigma B is thought to control a general
      stress regulon, the range of cellular functions it directs remains largely
      unknown. Our approach to understand the physiological role of sigma B is to
      characterize genes that require this factor for all or part of their expression,
      i.e. the csb genes. In this study, we report that the transposon insertion
      csb40::Tn917lac identifies an operon with three open reading frames, the second
      of which resembles plant proteins induced by desiccation stress. Primer-extension
      and operon-fusion experiments showed that the csb40 operon has a sigma B
      dependent promoter which is strongly induced by the addition of salt to
      logarithmically growing cells. The csb40 operon also has a second, sigma H
      dependent promoter that is unaffected by salt addition. These results provide
      support for the hypothesis that sigma B controls a general stress regulon, and
      indicate that the sigma B and sigma H regulons partly overlap. We suggest that in
      addition to its acknowledged role in the sporulation process, sigma H is also
      involved in controlling a subclass of genes that are broadly involved in a
      general stress response.

PMID- 8733233
TI  - DNA supercoiling depends on the phosphorylation potential in Escherichia coli.
AB  - ATP/ADP ratios were varied in different ways and the degree of negative
      supercoiling was determined in Escherichia coli. Independent of whether the ATP/
      ADP ratio was reduced by a shift to anaerobic conditions, by addition of a
      protonophore (dinitrophenol) or by potassium cyanide addition, DNA supercoiling
      decreased similarly with the ATP/ADP ratio. The experiments were performed under
      well-defined conditions, where oxidative phosphorylation was the dominant route
      for ATP synthesis, i.e. using a minimal salts medium with succinate as the sole
      free-energy and carbon source, and in the presence or absence of ammonia as the
      nitrogen source. The results of the different experiments were consistent with a
      single linear relationship between the log(ATP/ADP) and the change in linking
      number. The dependence of DNA supercoiling on the ATP/ADP ratio was not
      influenced by inhibitors of transcription or translation. Because the ATP/ADP
      ratio was modulated in different ways, the unique relationship suggests coupling
      between the phosphorylation potential and DNA supercoiling. This was most
      probably mediated by the DNA gyrase, independent of topoisomerase I or
      transcription.

PMID- 8733234
TI  - Optimized BlaM-transposon shuttle mutagenesis of Helicobacter pylori allows the
      identification of novel genetic loci involved in bacterial virulence.
AB  - Helicobacter pylori is an important etiologic agent of gastroduodenal disease in
      humans. In this report, we describe a general genetic approach for the
      identification of genes encoding exported proteins in H. pylori. The novel TnMax9
      mini-blaM transposon was used for insertion mutagenesis of a H. pylori gene
      library established in Escherichia coli. A total of 192 E. coli clones expressing
      active beta-lactamase fusion proteins (BlaM+) were obtained, indicating that the
      corresponding target plasmids carry H. pylori genes encoding putative
      extracytoplasmic proteins. Natural transformation of H. pylori P1 or P12 using
      the 192 mutant plasmids resulted in 135 distinct H. pylori mutant strains (70%).
      Screening of the H. pylori collection of mutant strains allowed the
      identification of mutant strains impaired in motility, in natural transformation
      competence and in adherence to gastric epithelial cell lines. Motility mutants
      could be grouped into distinct classes: (i) mutant strains lacking the major
      flagellin subunit FlaA and intact flagella (class I); (ii) mutant strains with
      apparently normal flagella, but reduced motility (class II), and (iii) mutant
      strains with obviously normal flagella, but completely abolished motility (class
      III). Two independent mutations that exhibited defects in natural competence for
      genetic transformation mapped to different genetic loci. In addition, two
      independent mutant strains were isolated by their failure to bind to the human
      gastric carcinoma cell line KatoIII. Both mutant strains carried a transposon in
      the same gene, 0.8 kb apart, and showed decreased autoagglutination when compared
      to the wild-type strain.

PMID- 8733235
TI  - Co-operative binding of two Trp repressor dimers to alpha- or beta-centred trp
      operators.
AB  - The alpha-centred trp operator binds one dimer of the Trp repressor, whereas the
      beta-centred trp operator binds two dimers of the Trp repressor (Carey et al.,
      1991; Haran et al., 1992). The Trp repressor with a Tyr-Gly-7 substitution binds
      almost as well as the wild-type Trp repressor to the alpha-centred trp operator,
      but it does not bind to the beta-centred trp operator. This confirms that Tyr-7
      is involved in the interaction between Trp repressor dimers, as seen in the
      crystal structure (Lawson and Carey, 1993). Further experiments with alpha
      centred trp operator variants showed that positions +/-1 of the alpha-centred trp
      operators play a crucial role in tetramerisation. The two innermost base pairs of
      the alpha-centred trp operator are not involved in contacts with the dimer of the
      Trp repressor binding to it. However, substitutions in these positions (T-A to G
      T) effectively transform the alpha-centred trp operator into a beta-centred trp
      operator, and thus encourage the binding of two Trp repressor dimers to this
      operator. Finally, we demonstrate, with suitable heterodimers, that one subunit
      of each dimer suffices to bind to a beta-centred trp operator.

PMID- 8733236
TI  - A 38 kDa precursor protein of aqualysin I (a thermophilic subtilisin-type
      protease) with a C-terminal extended sequence: its purification and in vitro
      processing.
AB  - The precursor of aqualysin I, an extracellular subtilisin-type protease produced
      by Thermus aquaticus, consists of four domains: an N-terminal signal peptide, an
      N-terminal pro-sequence, a protease domain, and a C-terminal extended sequence.
      In an Escherichia coli expression system for the aqualysin I gene, a 38 kDa
      precursor protein consisting of the protease domain and the C-terminal extended
      sequence is accumulated in the membrane fraction and processed to a 28 kDa mature
      enzyme upon heat treatment at 65 degrees C. The 38 kDa precursor protein is
      separated as a soluble form from denatured E. coli proteins after heat treatment.
      Accordingly, purification of the 38 kDa proaqualysin I was performed using
      chromatography. The purified precursor protein gave a single band on SDS
      polyacrylamide gels. The precursor protein exhibited proteolytic activity
      comparable to that of the mature enzyme. The purified precursor protein was
      processed to the mature enzyme upon heat treatment. The processing was inhibited
      by diisopropyl fluorophosphate. The processing rate increased upon either the
      addition of mature aqualysin I or upon an increase in the concentration of the
      precursor, suggesting that the cleavage of the C-terminal extended sequence
      occurs through an intermolecular self-processing mechanism.

PMID- 8733237
TI  - Purification and functional characterization of PecS, a regulator of virulence
      factor synthesis in Erwinia chrysanthemi.
AB  - The Erwinia chrysanthemi pecS gene encodes a repressor that negatively regulates
      the expression of virulence factors such as pectinases or cellulases. The cloned
      pecS gene was overexpressed using a phage T7 system. The purification of PecS
      involved DEAE-anion exchange and TSK-heparin columns and delivered the PecS
      protein that was purified to homogeneity. The purified repressor displayed an 18
      kDa apparent molecular mass and an isoelectric point near to neutrality (pl =
      6.5). Gel-filtration experiments revealed that the PecS protein is a dimer.
      Bandshift assays demonstrated that the PecS protein could specifically bind in
      vitro to the regulatory sites of the in vivo PecS-regulated genes. The
      interaction between the PecS protein and its DNA-binding site was characterized
      by a relatively low affinity (about 10(-8) M). DNase I footprintings revealed
      short protected sequences only with the most in vivo PecS-regulated genes.
      Alignment of these PecS-binding sites did not show a well-conserved consensus
      sequence. Immunoblotting demonstrated that the copy number of the PecS protein
      was approximately 50 dimers per cell. The low affinity of the PecS repressor for
      its DNA targets and the low cellular PecS content suggest the existence of E.
      chrysanthemi-specific factors able to potentiate PecS protein activity in vivo.

PMID- 8733238
TI  - Tandem genes encode cell-surface polypeptides SspA and SspB which mediate
      adhesion of the oral bacterium Streptococcus gordonii to human and bacterial
      receptors.
AB  - The highly conserved antigen I/II family of polypeptides produced by oral
      streptococci are believed to be colonization determinants and may mediate
      adhesion of bacterial cells to salivary glycoproteins absorbed to cells and
      tissues in the human oral cavity. Streptococcus gordonii is shown to express, on
      the cell surface, two antigen I/II polypeptides designated SspA and SspB
      (formerly Ssp-5) that are the products of tandemly arranged chromosomal genes.
      The structure and arrangement of these genes is similar in two independently
      isolated strains, DL1 and M5, of S. gordonii. The mature polypeptide sequences of
      M5 SspA (1539 amino acid (aa) residues) and SspB (1462 aa residues) are almost
      wholly conserved (98% identical) in the C-terminal regions (from residues 796 in
      SspA and 719 in SspB, to the respective C-termini), well-conserved (84%) at the N
      terminal regions (residues 1-429), and divergent (only 27% identical residues)
      within the intervening central regions. Insertional inactivation of the sspA gene
      in S. gordonii DL1 resulted in reduced binding of cells to salivary agglutinin
      glycoprotein (SAG), human erythrocytes, and to the oral bacterium Actinomyces
      naeslundii. Further reductions in streptococcal cell adhesion to SAG and to two
      strains of A. naeslundii were observed when both sspA and sspB genes were
      inactivated. The results suggest that both SspA and SspB polypeptides are
      involved in adhesion of S. gordonii cells to human and bacterial receptors.

PMID- 8733239
TI  - Autoregulation of luxR: the Vibrio harveyi lux-operon activator functions as a
      repressor.
AB  - Mobility-shift assays have been used to demonstrate that the activator of the
      Vibrio harveyi lux operon, LuxR, binds independently, and with similar affinity,
      to two sites upstream of its own open reading frame. One site was located between
      52 and 107 bp upstream of, and the other site in a region 25 bp downstream of,
      the transcriptional start site. The luxR promoter, in a transcriptional fusion
      with the chloramphenicol acetyl transferase (cat) gene, could readily be
      expressed in Escherichia coli as well as V. harveyi in the absence of LuxR. In
      both species, the presence of the luxR gene product resulted in repression of
      luxR promotion. These results show that LuxR directly regulates its own
      expression by functioning as an autorepressor. A mechanism for this repression is
      suggested by evidence showing that LuxR has a negative effect on RNA polymerase
      binding to the luxR promoter. In light of the fact that LuxR is also part of a
      regulatory family of repressors, the mechanism by which LuxR functions as a
      transcriptional activator of the lux operon has been re-examined.

PMID- 8733240
TI  - Multiple copies of MATE elements support autonomous plasmid replication in
      Aspergillus nidulans.
AB  - The AMA1 sequence is an efficient plasmid replicator and transformation enhancer
      in Aspergillus nidulans. It comprises two long perfect inverted repeats (MATE
      elements) flanking a short, unique, central spacer. Subclone analysis indicates
      that the complete inverted duplication, but not the unique central spacer, is
      necessary for efficient plasmid replication. The smallest fragments able to
      affect transformation efficiency lie within the AT-rich portions of the inverted
      repeats. We demonstrate that two or more copies of the repeat in any relative
      orientation are able to perform the replicator function. A single copy of a MATE
      element increases transformation frequency to a modest extent but leads to
      multiple rearrangement, unstable integration or concatenation of vector
      molecules. Multimeric concatenates generated during this process are more sable
      mitotically, and when reisolated, transform the fungus at a much higher frequency
      than the original monomeric vector. Selection for multiple products which
      resemble amplified DNA in various eukaryotic systems.

PMID- 8733241
TI  - Reciprocal regulation of the differentiation of Myxococcus xanthus by Pkn5 and
      Pkn6, eukaryotic-like Ser/Thr protein kinases.
AB  - Myxococcus xanthus contains a large family of genes encoding eukaryotic-like
      serine/threonine kinases. Among them, two genes, pkn5 and pkn6, are divergently
      located on the chromosome and share a 46 bp promoter region between their
      transcription initiation sites, as determined by RNA protection. Pkn5, consisting
      of 380 amino acid residues, is a soluble protein in the cytoplasm, while Pkn6,
      consisting of 710 amino acid residues, is a transmembrane protein. Its membrane
      topology was determined using the Pkn6-PhoA fusion protein in Escherichia coli,
      which has a single transmembrane domain with the N-terminal domain in the
      cytoplasm and the C-terminal domain outside the cytoplasmic membrane. Both
      proteins, when expressed in E. coli, were autophosphorylated: Pkn5 only at Ser,
      and Pkn6 at both Ser and Thr. In M. xanthus, both genes are expressed
      constitutively throughout the life cycle, with slight increases at an early stage
      of development. Most strikingly, a pkn5-deletion strain forms fruiting bodies
      much faster than the wild-type strain, while a pkn6-deletion strain develops
      slower than the wild-type strain. These results, together with the fact that the
      pkn5-deletion strain is able to form fruiting bodies on semi-rich media, suggest
      that Pkn5 and Pkn6 have reciprocal roles in M. xanthus growth and development.
      Furthermore, Pkn6 may be a transmembrane sensor of external signals for
      development, while Pkn5 is a kinase that negatively regulates M. xanthus
      development.

PMID- 8733242
TI  - Regulation by low temperatures and anaerobiosis of a yeast gene specifying a
      putative GPI-anchored plasma membrane protein [corrected].
AB  - Expression of the yeast Saccharomyces cerevisiae SRP1 (Serine-rich Protein) gene
      is shown here to be induced both by low temperature and anaerobic growth
      conditions. We show that anaerobic SRP1 expression is haem-dependent; however,
      haem influence does not operate through the action of the hypoxic-gene ROX1
      repressor. The SRP1 promoter region displaying the stress-responsive elements is
      restricted to its first 551 bp, upstream of the initiation codon, although an
      upstream activation site contained in upstream sequences is required for full
      promoter activity. In addition, we demonstrate that the TIP1 gene, sharing
      similar nucleotide and polypeptide structure with SRP1, and previously reported
      to be a cold-shock-inducible gene, is also a hypoxic gene. Srp1 protein
      production is similarly induced by low temperature and anaerobic growth
      conditions. This protein, detected in the plasma membrane fraction, is shown to
      be exposed on the cell surface via a glycosyl-phosphatidylinositol membrane
      anchoring.

PMID- 8733243
TI  - [Left ventricular hypertrophy and its regression in systemic arterial
      hypertension].

PMID- 8733244
TI  - [Plasma kallikrein clearance by the liver in experimental cirrhosis].
AB  - AIM: To study the hepatic clearance of a glycoprotein (rat plasma kallikrein) by
      the liver of rats with experimental decompensated cirrhosis. MATERIAL AND
      METHODS: Cirrhosis was induced by intragastrically administration of carbon
      tetrachloride 520 mg/kg/week, during 16-19 weeks. After this period, each liver
      was isolated, exsanguinated and perfused at 37 degrees C with 10nM rat plasma
      kallikrein (RPK). RESULTS: 58% of the animals died during the treatment and the
      remaining developed prostration, ascites, jaundice and bleeding; at the end of
      the treatment period serum aminotransferases were not altered and serum albumin
      decreased. The liver histology showed cirrhosis. RPK clearance rate of the
      cirrhosis group (5.4 +/- 0.9 pmol/g liver/10 min) was significantly lower (p <
      0.05) than that of the control group (13.5 +/- 2.7 pmol/g liver/10 min).
      CONCLUSION: The development of cirrhosis is associated with a decreased hepatic
      clearance of a glycoprotein which endocytosis is mediated by a receptor.

PMID- 8733245
TI  - [Antithrombin III dosage using the chromogenic substrate Tos-Gly-Pro-Arg-NAN, in
      several pathological situations].
AB  - Functional methods for ATIII determination are essential for the diagnosis of
      deficiencies of this important thrombin inhibitor. PURPOSE: The aim of this work
      was standardize the method for ATIII level determination in plasma, in
      microplates. METHOD: ATIII levels were measured, using the chromogenic substrate
      Tos-Gly-Pro-Arg-NAN, which is specific for thrombin, and which has been
      sinthesized at the Biophysical Department of the Escola Paulista de Medicina of
      the Federal University of Sao Paulo, Brazil. RESULTS: Among 21 patients with deep
      venous thrombosis (DVT), 20 had ATIII levels above 70% (113 +/- 22%). A 22 year
      old female patient, who had recurrent DVT and a familiar DVT antecedent, had a
      congenital ATIII deficiency (56%). ATIII levels were normal in 6 patients with
      von Willebrand disease (109 +/- 28%), as expected. In 20 patients with severe
      hepatic failure, it has been found reduced ATIII levels (42 +/- 19%), since this
      inhibitor is produced by the liver. In 3 patients with sepsis and DIC, ATIII
      levels have also been reduced (45 +/- 5%) owing to consumption during blood
      coagulation activation. There was a significant correlation between ATIII levels
      and the prothrombin time, as well as the factor V levels, and both are good
      parameters to assess hepatic function and to monitor DIC. There was a significant
      correlation between ATIII levels measured using the chromogenic substrate Tos-Gly
      Pro-Arg-NAN and those measured using S-2238, produced by Kabi Laboratories.
      CONCLUSIONS: This method for ATIII determination in plasma is easy to perform and
      it can detect ATIII deficiency in patients with hepatic failure, disseminated
      intravascular coagulation and thrombophilia.

PMID- 8733246
TI  - [Analysis of the program of control of the use of antimicrobials at the Hospital
      Sao Paulo--Escola Paulista de Medicina].
AB  - BACKGROUND AND OBJECTIVE: Antimicrobial agents represent a group of drugs that
      are frequently used in hospitals. Approximately, 50% of hospitalized patients
      receive at least one antimicrobial drug during the hospitalization period.
      However, half of these drugs are prescribed incorrectly. The objective of this
      paper was to analyse the antimicrobial control program that has been used at
      Escola Paulista de Medicina since 1989. CASUISTIC & METHODS: The prescription of
      eleven controlled antibiotics should be done in a special form. Any requisition
      of a controlled antibiotic was evaluated, within 24 hours, by an infection
      diseases specialist who was hired exclusively for this function. RESULTS: During
      1989, 5,573 controlled antimicrobials were requested by the hospital staff, and
      17.6% of them were considered inadequate and were refused. Such a percentage was
      high considering that our institution is a university hospital where the
      antibiotic usage should be more precise and adequate. We also should take into
      account that the indication of only 11 antimicrobial drugs were evaluated.
      CONCLUSION: The results allow us to conclude that each hospital should have not
      only a policy on antimicrobial usage but also an effective program of control of
      these drugs.

PMID- 8733247
TI  - [Graduation in Medicine: admission criteria vs. scientific production].
AB  - Medical postgraduation in Brazil is divided into two categories: lato sensu
      (residency and fellowship) and stricto sensu (MSc, PhD), being the former a
      prerequisite to the latter. The author presents a study comparing two
      postgraduation courses in which both lato and stricto sensu are available, in
      order to determine if their selection criteria for the MSc/PhD courses are
      protective for their own residents (endogenic) and the consequences to their
      scientific production. The information concerning selection criteria and
      endogenic proportion was obtained directly from the courses' offices. To evaluate
      the scientific production, the Ellwein et al. (1989) method, modified, was used:
      number of papers published in the two major Brazilian journals of the specialty,
      in which there was, at least, one post-graduation student and the position in the
      byline as well. Period considered: 1983-1992. For ethical reasons the courses
      were named by greek letters "beta" and "gamma". "Beta" selects mainly by the
      curriculum vitae. It had an endogenic proportion of 29.4% (34/116), a mean
      scientific production of 8.6 +/- 4.3 papers/year that, when considered
      proportionally (total number of papers/total number postgraduate students) gives
      us the value of 0.74 (74%). "Gamma" prefers a test in the specialty and the
      questions come from lectures given in its residency course. Respectively, the
      "gamma" results were: 93.5% (56/60), 15 +/- 14 and 0.25 (25%). The differences
      between "beta" and "gamma" were statistically significant (p < 0.001). The author
      concludes that a high endogenic proportion acts negatively in the scientific
      production of a stricto sensu (Master and PhD) Brazilian course. Different ways
      to select are also discussed.

PMID- 8733248
TI  - [Stricto sensu graduation in medicine].
AB  - During the last thirty years, the postgraduate course stricto sensu reached its
      maturity. Its main purpose is to prepare university professors, by updating them
      in specific areas of knowledge, and teaching them how to carry out scientific
      works. Few major advisors, little financial support and lack of association with
      other courses and institutions are the limiting factors. The limits related to
      the postgraduate students are the diversity, the deviation from the professional
      activity and the isolation of the students in a strange environment. The
      advantages brought by this course justify investments in its growth and
      consequent development of the university.

PMID- 8733249
TI  - [Surgical treatment of stress urinary incontinence: analysis of the results by
      abdominal or vaginal pathways].
AB  - BACKGROUND: The postoperative results of 367 surgical interventions for the
      correction of urinary stress incontinence were analyzed in terms of time of onset
      and occurrence of relapses. MATERIAL AND METHOD: The cases were assigned to four
      groups: A = 206 cases of Kelly-Kennedy surgery (56.1%); B = 37 cases of Kelly
      Kennedy surgery associated with vaginal hysterectomy (10.1%); C = 95 cases of
      Burch surgery (25.9%), and finally, D = 29 cases of Burch surgery associated with
      total abdominal hysterectomy (7.9%). RESULTS: Postoperative follow-up ranged from
      1 to 194 months, with a mean of 31 months. The incidence of relapses was 20.7% in
      group D, and 10.8% in group B. In 68.7% of the surgical interventions by vaginal
      route and in 82.3% of interventions by abdominal route, the relapses occurred
      within less than three years. CONCLUSION: The results were not different in the
      groups. The relapses occurred within less than three years in most cases.

PMID- 8733250
TI  - [Practical aspects of organ procurement for transplant].

PMID- 8733251
TI  - [Botulin toxins in the treatment of spasmodic torticollis].

PMID- 8733252
TI  - [Helicobacter pylori: comparative study of different diagnostic techniques].
AB  - OBJECTIVE: To compare the different diagnostic techniques of Helicobacter Pylori
      infection, confronting the bacteriological culture to other faster, less
      expensive and easier techniques, such as the urease test, methylen blue and Gram
      stained smears, the histopathologic examination of biopsies specimens, and the
      detection of IgG antibodies anti Helicobacter Pylori. MATERIAL AND METHODS: 43
      patients with gastroduodenal symptoms who had not taken NSAIDs and who presented
      endoscopic signs of inlammation and/or gastroduodenal ulcer were prospectively
      studied. Biopsies specimens of antrum, gastric fundus and duodenal bulb were
      taken and processed in the following way: methylen blue and Gram stained smears
      and Hematoxylin and eosin stained section. Studies were performed in to all the
      43 patients. Urease test was performed in the antrum specimens of 37 patients,
      and inmunologic test by inmunoenzimatic technique (ELISA) in 40 of them. RESULTS:
      Methylen blue and Gram stained smears: sensitivity (S): 100% and specificity (E):
      76% Histopathologic examination (S): 86% (E): 61%, urease test (S) 100% (E)
      62.5%, antibodies anti H.P. not possible to calculate. DISCUSSION: The authors
      have taken the microbiological culture as a reference technique because the
      isolation and identification of the bacteria are the most important signs of its
      presence and vitality. Stained smears, histopathologic examination and the urease
      test are fast, inexpensive techniques with high sensitivity for diagnosis.
      However, the inmunologic test is reveals better to the prevalence of the
      infection.

PMID- 8733253
TI  - Abnormal colonic transit time in untreated celiac sprue.
AB  - Motility disorders of the digestive tract have long been implicated in the
      pathophysiology of diarrhea in patients with celiac sprue. However, the
      contribution of the colon to the intestinal transit of celiac sprue has not been
      reported. Our aim was to determine whether sprue alters gut transit and whether
      differences in the clinical status of the disease influences colonic transit. We
      prospectively studied 25 patients with untreated celiac sprue, 15 treated
      patients and 15 healthy controls. Oro-cecal transit time, measured by the
      lactulose breath H2 test, was significantly delayed in untreated patients
      compared with treated patients and controls (p < 0.001 and p < 0.01
      respectively). The delayed transit through the stomach and small bowel was not
      related to the presence of the steatorrhea. Transit of radiopaque makers, a
      measure of total colonic transit, was significantly faster in untreated patients
      (p < 0.05). The major finding was that this abnormal colonic behavior was
      principally due to a subpopulation of untreated patients with very fast transit
      times (< 18 hours). A weakly significant inverse correlation between transit and
      fecal weight (r: -0.55, p < 0.01), and between transit and steatorrhea (r: -0.38,
      p < 0.05), was observed. We confirm previous descriptions of delayed oro-cecal
      transit time in untreated patients, and also provide the first evidence that
      disordered colonic transit contributes to the pathophysiology of the diarrhea in
      sprue.

PMID- 8733254
TI  - [Diagnostic efficacy of albumin gradient in different causes of ascitis].
AB  - The aim of this study was to compare the serum-ascites albumin gradient (GS-A) to
      the transudate-exudate concept in the classification of ascites. The second
      objective was to analyze the predictive value and efficacy of GS-A, ascites total
      protein, LDH, Ratio and ascites cholesterol in patients with liver disease and
      malignant ascites. For this purpose we studied prospectively 98 patients (in
      prospective form). The transudate-exudate concept classified correctly the causes
      of ascites only in 65.6% of the patients. In contrast, the GS-A did it 95.7% of
      the patients. In differentiating ascites caused either by chronic liver disease
      or by malignancy, the tests with best efficacy were cholesterol (98%),
      (predictive value 97%) and GS-A efficacy 94% (predictive value 94%). We conclude
      that GS-A was better than the traditional transudate-exudate concept in
      classification of ascites. The test with the best efficcacy separating ascites
      caused by chronic liver disease or by malignancy was the ascites cholesterol.

PMID- 8733255
TI  - [Massive pleural effusion in liver cirrhosis without ascites].
AB  - We present two patients with masive pleural effusion, asociated to cirrhosis.
      There was no clinical evidence of ascites, and in the first case it didn't even
      show up in the CT scanning. Al other posible causes were discarded and the
      therapeutic response was analysed. We evaluated the pathophysiologic mechanisms
      of the syndrome and we suggest the pneumoperitoneum as a diagnostic procedure
      which is easy to apply and carries low costs.

PMID- 8733256
TI  - [Esophageal stenosis in children. Management with dilatation techniques (part
      II)].

PMID- 8733257
TI  - Pepsinogens and pepsins: aggresion on gastric mucosa and Helicobacter influence.

PMID- 8733258
TI  - [Diagnostic methods for the detection of Helicobacter pylori. Old and new
      techniques].

PMID- 8733259
TI  - [Value of serologic markers in the management of colorectal cancer].

PMID- 8733260
TI  - [Seroprevalence of Epstein Barr virus infection in a healthy population of
      Santiago de Chile].
AB  - To study the rate of infection by Epstein Barr virus (EBV) in Santiago, Chile,
      the prevalence of antibody to the viral capsid antigen (VCA-IgG) was determined
      in a group of 663 healthy individuals grouped by age and socioeconomic level
      (SEL). In addition, several risk factors for infection were studied. VCA-IgG was
      determined by ELISA. The total prevalence was 76.7%. When grouped by age and SEL,
      50% of the children from low and medium SEL had been already infected by the age
      two, compared to 5.9% in the high SEL (p < 0.01). However, by age twenty, 90% of
      the total sample had already specific antibodies to EBV. Age and number of
      household members were positively associated with the infection. High
      socioeconomic level represented a delay factor in the acquisition of the virus,
      (p < 0.01). These results show that EBV infection is frequent in Santiago,
      occurring early in childhood among medium and low SEL. Hence, the classical
      infectious mononucleosis should be recognized more frequently among adolescents
      and young adults belonging to high SEL, while the clinical spectrum of associated
      manifestations different from the typical mononucleosis syndrome should be
      investigated among those exposed in early age.

PMID- 8733261
TI  - [Bacterial translocation in a model of small intestine autotransplant in dogs].
AB  - BACKGROUND: Sepsis is the commonest complication of small bowel transplantation.
      These infections are presumably caused by bacterial translocation, due to
      splanchnic ischemia. AIM: To study bacterial translocation in the immediate
      postoperative period after a small bowel transplantation in dogs and to relate it
      to splanchnic ischemia. METHODS: Three groups of dogs were studied. In group A (n
      = 6) spontaneous episodes of splanchnic ischemia were monitored in the first 18 h
      of the postoperative period. In group B (n = 5), a 60 min ischemia was induced by
      superior mesenteric artery occlusion, two hours after small bowel
      transplantation. In group C (n = 5) a 60 min ischemia was induced by occlusion of
      mesenteric vein, two hours after transplantation. Bacterial translocation was
      assessed through bacterial cultures from the mesenteric vein and splanchnic
      ischemia with intramucosal pH measurement (a pH < 7.2 was considered indicative
      of ischemia). RESULTS: Twenty eight of 83 cultures were positive, specially for
      Gram negative bacilli. The incidence of positive cultures was 14% for group A,
      17% for group B and 79% for group C (p < 0.01 compared to groups A and B). The
      higher incidence of bacterial translocation occurred during the first two hours
      after transplantation, when the lower intramucosal pH recordings were obtained.
      The percentage of positive cultures was 39% during periods of ischemia, compared
      to 24% during periods without ischemia (p = NS). CONCLUSIONS: Bacterial
      translocation occurs during the first two hours after intestinal transplantation,
      in concomitance with the lower intramucosal pH readings.

PMID- 8733262
TI  - [Evaluation of ELISA and counterimmunoelectrophoresis in diagnosis of human
      neurocysticercosis in Chile].
AB  - The aim of this work was to assess the diagnostic accuracy for
      neurocysticercosis, of ELISA and counterimmunoelectrophoresis techniques, in sera
      and cerebrospinal fluid. Two hundred eight serum samples (47 coming from patients
      with confirmed cysticercosis) and 87 cerebrospinal fluid samples (27 coming from
      patients with confirmed cysticercosis) were analyzed. A crude and standardized
      extract of swine muscle cysticercus cellulose was used as antigen. ELISA and
      counter immunoelectrophoresis had a 100% specificity in cerebrospinal fluid. In
      sera, counterimmunoelectrophoresis had a 94.1% specificity. In sera and
      cerebrospinal fluid, ELISA had a 85.1% sensitivity. Cross reactions were observed
      in sera of patients with confirmed hydatidosis. Thus, the high specificity of
      both techniques in cerebrospinal fluid is probably due to the low incidence of
      cerebral hydatidosis in Chile. It is concluded that for the diagnosis of
      neurocysticercosis, antibodies against cysticercus cellulosae must be sought
      paralelly in serum and cerebrospinal fluid using ELISA and
      counterimmunoelectrophoresis.

PMID- 8733263
TI  - [Non-invasive intermittent mechanical ventilation: usefulness in treatment of
      chronic severe heart failure].
AB  - BACKGROUND: The higher respiratory work and less inspiratory muscle strength of
      patients with cardiac failure may contribute to decrease their functional
      capacity. AIM: To assess the effects of non invasive intermittent mechanical
      ventilation on clinical parameters, peripheral perfusion, cardiac and inspiratory
      muscle function. PATIENTS AND METHODS: Patients with chronic cardiac failure,
      functional capacity III-IV were subjected to 6 sessions of nasal non invasive
      intermittent ventilation during 4 hours or to simulated ventilation (controls).
      RESULTS: Fifteen ventilated patients and six controls completed the protocol.
      Ventilated patients improved the Mahler transition score for dyspnea by 4 +/- 1.6
      points. They also improved their aerobic capacity, increasing the exercise
      duration from 10.9 +/- 4 to 12.7 +/- 5 min and their maximal oxygen consumption
      from 14.6 +/- 4 to 16.4 +/- 5.7 ml/kg/min. These patients also decreased their O2
      and CO2 ventilatory equivalents. Maximal inspiratory pressure increased from 67.9
      +/- 23.6 to 80.19 +/- 21.4 cm H2O, sustained maximal inspiratory pressure
      increased from 101.4 +/- 48 to 133 +/- 53 cm H2O and maximal endurance increased
      from 132 +/- 52 to 162 +/- 58 g in ventilated patients. None of these variables
      was modified in control patients. No changes were observed in renal function,
      blood volume, arterial gases, spirometry or plasma catecholamine levels in any
      group. CONCLUSIONS: Intermittent nasal ventilation or other measures to improve
      inspiratory muscle function may be beneficial for patients with severe cardiac
      failure.

PMID- 8733264
TI  - [Delayed puberty and hypogonadotrophic hypogonadism: differential diagnosis with
      prolactin stimulation probe with chlorpromazine].
AB  - We studied the changes in plasma levels of prolactin after an intramuscular
      injection of 0.33 mg/kg chlorpromazine and changes in plasma levels of LH and FSH
      after the injection of 100 micrograms iv GnRH, in 16 patients with delayed
      puberty, 10 patients with hypogonadotrophic hypogonadism and 6 healthy controls.
      Prolactin response was significantly lower in patients with hypogonadotrophic
      hypogonadism compared to subjects with constitutional delayed and healthy
      controls (delta Prolactin 7.05 +/- 1.7, 28.9 +/- 2.7 and 22.0 +/- 3.4 ng/ml
      respectively). LH response to GnRH was also lower in patients with
      hypogonadotrophic hypogonadism, compared to the other two groups (delta LH 4.3 +/
      2.5, 13.4 +/- 5.4 and 17.2 +/- 4.8 mUI/ml respectively) however, there was a
      great overlapping of values. No differences between groups were observed in
      responses of FSH, testosterone and estrogens to GnRH. It is concluded that
      prolactin response to chlorpromazine is useful in the differential diagnosis of
      constitutional delayed puberty.

PMID- 8733265
TI  - [Hospitalization in the elderly patient: a risk or benefit?].
AB  - The aim of this work was to study the impact of hospital admission on functional
      status of elders. Eighty six patients (63 male) aged 73 +/- 4 years old admitted
      to the Internal Medicine Service of a public hospital were studied. Functional
      status was measured on admission, discharge and 15 days after discharge using the
      Northwestern Functional Status Review Instrument. Fifteen patients died during
      hospital stay. Functional status improved in patients admitted with disordered
      consciousness, in those admitted due to neurologic disorders, in those with less
      than two chronic diseases, in those whose disease cured during hospitalization
      and those that did not acquire new disease during admission. Prolonged
      hospitalizations of more than 13 days were associated with functional status
      worsening. It is concluded that functional status or elders does not always
      deteriorate during hospital admissions.

PMID- 8733266
TI  - [Retrograde cerebral perfusion during circulatory arrest with deep hypothermia. A
      new technique for brain protection in surgery of ascending aorta and aortic
      arch].
AB  - Between May 1993 and August 1994, 15 patients (10 men) with type A aortic
      dissection (9 acute) had a replacement of the ascending aorta and/or aortic arch
      with circulatory arrest with profound hypothermia and retrograde cerebral
      perfusion. Mean circulatory arrest time was 47.5 min (range 23 to 68 min). Three
      patients (20%) died in relation to postoperative bleeding. No patient had a new
      neurologic damage related to surgery. Ten patients were awake and oriented before
      24 hours of the operation and another one before 48 hours; 4 patients required
      more than 48 hours to be completely awake and oriented. Two patients were
      operated on with a recent stroke. One of them recovered without sequelae before
      hospital discharge and the other one had a major regression of his brain damage.
      Two other patients had emergency surgery because of cardiac tamponade and
      cardiogenic shock. Both of them had a satisfactory recovery. Six patients
      presented azotemia but only 2 of them needed dialysis. There was no case of Q
      wave infarction nor congestive heart failure in the perioperative period. Follow
      up was 100% completed (12 patients) with a mean of 9.8 months (range 5 to 18
      months). One patient died on the 10th postoperative month because of a late
      infectious process. Eight patients are in functional class I and 3 in II. Ten of
      them are back to their usual activities'. Although retrograde cerebral perfusion
      is a new surgical technique, it seems to be a very valuable complement for brain
      protection in ascending aorta and/or aortic arch surgery with circulatory arrest
      with profound hypothermia.

PMID- 8733267
TI  - [Algorithm management for detection of monoclonal gammopathies in serum.
      Experience of the Instituto Nacional de Cancerologia in Mexico].
AB  - BACKGROUND: Most patients with multiple myeloma have an abnormal band in the
      gamma region of protein electrophoresis. AIM: To correlate the clinical diagnosis
      with patterns of protein electrophoresis. METHODS: Retrospective analysis of all
      protein electrophoresis or immunoglobulin quantification requested during 1992
      and review of clinical charts of patients. RESULTS: During 1992, 553 protein
      electrophoresis were requested. Of these, 344 were repetitions and 209 came from
      patients seen for the first time. Among the latter, we found a monoclonal
      component in 40. Of these 40 patients, 35 had a multiple myeloma, one had a
      plasmocytoma and four a non-Hodgkin lymphoma. Fourteen patients with diagnosis of
      myeloma did not have a monoclonal component in protein electrophoresis. These
      figures resulted in a 71% sensitivity and 97% specificity for monoclonal
      components in the diagnosis of multiple myeloma. The monoclonal component of
      patients with myeloma was characterized as IgG in 29 (60%), IgA in 5 (10%) and
      IgM in one. CONCLUSIONS: A monoclonal component present in a protein
      electrophoresis has a high diagnostic accuracy for multiple myeloma.

PMID- 8733268
TI  - [Fluconazole in treatment of urinary candidiasis. Experience with 24 patients].
AB  - Since fluconazole achieves high urine concentrations, we assessed its usefulness
      in the treatment of urinary candidiasis. We studied 24 patients (8 male) aged 23
      to 97 years old, that presented pyuria with a negative urine culture for bacteria
      and fungal colony counts in urine of 10(4) CFU/ml or more. Isolated strains were
      Candida albicans in 20 cases, Candida kefyr in one case, Candida glabrata in one
      case and Candida spp in two cases. All patients were treated with fluconazole in
      doses of 50 to 100 mg/day for 2 to 4 weeks. The fungus was eradicated in 21
      patients (88%), the infection persisted in two (8.5%) and one had a relapse
      (4.2%). Two patients had transient elevations of transaminases, one had abdominal
      pain and one, a purpuric syndrome without thrombocytopenia in whom the drug was
      discontinued. It is concluded that fluconazole is efficacious and safe in the
      treatment of urinary candidiasis.

PMID- 8733269
TI  - [Isolation of Coxsackieviruses B5 in a fatal case of meningoencephalitis].
AB  - A nine months old boy was admitted to the hospital with the diagnosis of
      meningoencephalitis 15 days after having a clinically diagnosed chickenpox.
      Lumbar puncture showed clear CSF with 0.23 g/l of proteins, 57 mg/dl of glucose,
      30 red cells/mm3 and 5 leukocytes/mm3. Blood count showed a packed red cell
      volume of 22%, a hemoglobin of 7 g/dl, 14800 leukocytes with 1% eosinophils, 5%
      band and 39% segmented neutrophils, 50% lymphocytes and 5% monocytes and a
      decreased platelet count. On the fourth hospitalization day, the patient had
      vomiting, irritability and stiff neck. A new lumbar puncture showed a clear CSF
      that differed from the former only in the glucose level that increased to 102
      mg/dl. The patient died and the necropsy showed a congestive and enlarged brain
      and congestive meninges infiltrated with lymphocytes. There was lymphoid follicle
      hyperplasia in the small bowel and enlarged mesenteric lymph nodes. Samples of
      brain, brain stem, spinal cord and stools were sent for virological study. A
      Coxsackie B-5 virus was isolated from the spinal cord sample.

PMID- 8733270
TI  - [Melkersson-Rosenthal syndrome: report of 3 cases].
AB  - Melkersson-Rosenthal syndrome is characterized by facial or lip edema, peripheral
      facial palsy and scrotal tongue. We report three patients with the syndrome. A 17
      years old male had malar and superior lip enlargement that coincided with a
      peripheral facial palsy. A 40 years old male with recurrent facial palsy
      presented with episodes of contralateral facial enlargement. A 32 years old
      female consulted for a hypertrophy of labia minora and majora and facial
      infiltration. Biopsies showed a granulomatous cheilitis in all cases. Two
      patients were treated with clofazimine with partial results. The female patient
      did not accept plastic surgery.

PMID- 8733271
TI  - [Body fat distribution: anthropometric indicators].
AB  - There are two types of fat distribution in obese subjects. The abdominal,
      superior, android or apple shaped and the gluteo-femoral, gynecoid, inferior or
      pear shaped. In the former, fat is accumulated in the abdomen and in the latter,
      in the gluteal region. The superior distribution is associated with a higher risk
      of cardiovascular diseases. Among anthropometric measurements of fat
      distribution, the ratio between waist circumference measured at the level of the
      navel and hip circumference, measured at the level of greater trochanters, is the
      best indicator. Using the cutoff points of 0.8 for women and 1 for men, it has a
      good correlation with visceral fat.

PMID- 8733272
TI  - [Informed consent].
AB  - The informed consent, in which the physician informs about procedures to be
      performed and requests approval, puts into practice the communication between
      physicians and patients. The consent will always be verbal and will only put
      writing in complex or risky situations. This doctrine, that promotes the
      recognition of patients autonomy, is employed since the end of World War II. Its
      main features are mental competence to know and elect, adequate and
      comprehensible information and voluntary acceptance or denial. In the situations
      of requested paternalism, therapeutic privilege and placebo use, information is
      not given and the consent is not requested. In all research protocols, a written
      informed consent must be requested. The consent is a form of communication that
      tries to defend patients rights as something close and alive, and should not
      become a ritual.

PMID- 8733273
TI  - [Utilitarian ethics in medicine?].

PMID- 8733274
TI  - [Malnutrition of the pregnant woman: an overestimated problem?].
AB  - The aim of this work was to compare the nutritional classification of pregnant
      women and their predictive value for low birth weight, using the criteria of the
      Ministry of Health (Rosso-Mardones curves) with the curves developed at the
      Department of Nutrition of the Faculty of Medicine and the body mass index. One
      thousand eight hundred four pregnant women of the Metropolitan Region, that were
      devoid of factors affecting birth weight, were studied retrospectively. Initial
      and final nutritional status was calculated according to the three criteria in
      study. Results showed that 47 to 75% of women classified as undernourished using
      Rosso-Mardones curves, were normal according to the curves of the Department of
      Nutrition and body mass index. Rosso-Mardones curves had the lower predictive
      value, relative risk and risk attributable to maternal nutritional deficit, for
      low birth weight. Also these curves showed a higher of obesity and a low
      predictive value for macrosomia. It is concluded that the curves used by the
      Ministry of Health must be revised.

PMID- 8733275
TI  - [Gallbladder cancer: immunohistochemical expression of the protein related to
      estrogen receptor (p29) and of the protein induced by estrogen (pS2)].
AB  - The high frequency of gallbladder cancer in women suggests a role for estrogens
      in its development. The aim of this study was to study the immunohistochemical
      expression of p29 estrogen receptor associated protein and pS2 estrogen induced
      protein in 111 pathological samples of gallbladder carcinoma, coming from 88
      women and 23 men, 30 metastases of gallbladder cancer, coming from 25 women and 5
      men and in 25 non-tumoral gallbladders. In the latter, p29 protein was positive
      in 12 samples (48%) and pS2 in 15 cases (60%). p29 was positive in 40% and pS2 in
      32% of tumors. p29 expressed with higher frequency in metastases than in primary
      tumors (57 and 31% respectively, p < 0.02). Early tumors had a significantly
      lower expression of p29 than advanced tumors or than metastases. Both proteins
      expressed in 18% of samples (synchronic expression) whereas one of both proteins
      did so in 60% of cases (asynchronic expression). We conclude that most
      gallbladder cancer samples express proteins associated to estrogen receptor or
      induced by estrogens.

PMID- 8733276
TI  - [Clinical and psychological characterization of children and adolescents with
      recurrent abdominal pain].
AB  - There is ample empirical evidence supporting the view of emotional disturbances
      in children with recurrent abdominal pain (RAP) as well as in their parents.
      However, controlled studies have reported that such manifestations can also be
      found in patients with other chronic ailments. In order to characterize further
      the nature of emotional factors in RAP patients, we conducted a controlled
      psychological evaluation of 46 consecutive new patients with RAP, aged 7-17
      years, (group A) by means of structured interviews and questionnaires. Two
      control groups of pediatric patients with chronic illnesses were also assessed
      using the same methodology. Group B consisted of 22 individuals with chronic
      abdominal pain and endoscopy-proven peptic ulcer or duodenitis, and group C
      consisted of 24 individuals with chronic, stable, non-gastroenterological
      diseases (e.g., diabetes mellitus or physical handicaps). Parents were evaluated
      for depressive symptoms. One-way analysis of variance and contingency tables were
      used for statistical comparisons. There was a higher proportion of female
      patients in group A than in group B (70 vs 41%; p < 0.05). There were
      significantly more patients in group A than in group B that reported that their
      abdominal pain: a) never appeared during sleep, b) began soon after the patient's
      arousal in the morning, c) remitted completely or was alleviated during school
      holidays, d) its remission was usually spontaneous during the day and e) did
      never interfere with recreational activities. Emotional problems were
      significantly more prevalent in patients in group B than in those in group A (p =
      0.016). Past diagnosis of depression was more frequent in group A mothers (40%)
      than in those in group B (27%), or group C (17%), but these differences did not
      attain statistical significance. These results suggest that psychological
      profiles of children suffering from certain chronic conditions (and those of
      their parents) may be more complex and particular than hitherto recognized. The
      role of type II error and of some potential socioeconomic and demographic
      confounding factors must be considered when analyzing the validity of these data.

PMID- 8733277
TI  - [Clinical evaluation of body hair in healthy women].
AB  - AIM: to study the amount and distribution of terminal body hair in non-hirsute
      women consulting in a public outpatient clinic. PATIENTS AND METHODS: two hundred
      thirty six premenopausal women consulting in a birth control clinic or consulting
      for acute non-endocrinological diseases were studied. Body hair was assessed with
      a semi-quantitative clinical method described by Ferriman and Gallwey. RESULTS:
      Ninety-five percent of women had a score equal or less than 5. No correlations
      were found between the score and body mass index or age. Partial scores over 1
      were found specially in the lower abdomen, chest, superior lip and thighs.
      CONCLUSIONS: This sample of women, coming from middle and low socioeconomic
      levels, appears more hairless than European or North American Women. Thus,
      hirsutism must be suspected with scores over 5. These results cannot be
      extrapolated to all Chilean women, due to differences in ethnical backgrounds.

PMID- 8733278
TI  - [Fulguration with radiofrequency of the slow nodal pathway: experience in 30
      consecutive cases].
AB  - Atrioventricular nodal reentry tachycardia (AVNRT) is one of the most frequent
      mechanisms of paroxysmal supraventricular tachycardia. In these patients
      tachycardia is maintained due to anterograde conduction through a slow pathway
      and retrograde conduction to the atrium via a fast pathway. We present herein our
      experience in ablation of the slow pathway. Since January 1993, 30 consecutive
      patients with AVNRT underwent attempted catheter ablation of the slow pathway.
      Mean age was 35 +/- 3.7 years. All patients had symptomatic tachycardia and six
      had history of syncope. Electrophysiologic studies revealed AVNRT in all
      patients, in addition, two patients had a left accessory pathway. Slow pathway
      ablation was performed with a Mansfield 7 F catheter, guided by both fluoroscopic
      positioning and endocardial signals. A mean of 13 bursts were applied. In the 30
      patients conduction through the slow pathway was interrupted, and thus
      tachycardia was no longer inducible. Retrograde conduction post ablation was
      evaluated in 17 of the 30 patients, significant changes were observed in three of
      them. One patient developed second degree AV block and a permanent pacemaker was
      implanted. Another patient had recurrence of tachycardia three months post
      ablation. After a second attempt she is arrhythmia free. Patients have been
      followed for a mean of 15.7 +/- 2.5 months and are asymptomatic in the absence of
      antiarrhythmic therapy.

PMID- 8733279
TI  - [Hospital course of acute myocardial infarction: significance of the therapeutic
      procedures of early reperfusion].
AB  - Reperfusion therapy has contributed to decreased morbidity and mortality in
      patients with acute myocardial infarction (AMI). Implementation of thrombolytic
      therapy; primary angioplasty and emergency coronary artery by-pass surgery have
      proved to be effective in well designed controlled clinical trials. There is
      little information, however, about the impact of reperfusion therapy in the
      general clinical population that is usually seen in the coronary care unit. In
      this paper we have compared the clinical course, morbidity and mortality of
      patients attended for a first AMI in 2 different periods. Group I comprised 431
      patients seen during the period 1981-1986 and group II bad 113 patients seen
      during the period 1992-1993. Age, gender distribution and AMI location were
      similar in both groups. Patients in group I had a significantly higher incidence
      of tobacco use and previous angina pectoris. In group I, 4% of patients received
      streptokinase, 0.9% of patients had emergency by-pass surgery and none had
      primary angioplasty, whereas in group II, 29% of patients received trombolytics,
      6.5% had primary angioplasty and 6.5% had by-pass surgery. Heart failure Killip
      class II-III occurred in 35% of patients in group I and in 13% of patients in
      group II (p < 0.05). Intrahospital mortality was 19.6% in group I and 11.5% in
      Group II (p < 0.045). There were no differences in the incidence of cardiogenic
      shock in both groups. Multivariate analysis showed that age and heart failure
      were significant independent predictors of mortality in both periods. Thus, there
      has been a significant change in the therapeutic approach to AMI patients in
      recent years. Widespread utilization of reperfusion therapy appears to be
      associated with decrease in morbidity and mortality in a general population of
      patients with a first AMI.

PMID- 8733280
TI  - [Vital prognosis in severe acute hepatic failure. Value of the quantitative
      indexes of evaluation].
AB  - The aim of this study was to assess the predictive value for mortality of
      admission and daily APACHE II score, mortality due to multiple organ failure and
      the Organ Failure Score in patients with acute hepatic failure. We
      retrospectively studied 15 such patients admitted to an intensive care unit.
      Thirteen patients died (87%) and their admission APACHE II score was 22 +/- 7.5
      compared to 21 +/- 8.5 in survivors. Daily APACHE II score, mortality due to
      multiple organ failure and multiple organ failure score had a 100% sensitivity to
      predict mortality and a 69.2, 76.9 and 76.9% specificity respectively. The
      predictive accuracies of multiple organ failure and multiple organ failure score
      were 80% and significantly better than the accuracy of admission APACHE II score
      (53%). We conclude that these prognostic scores can be useful in the assessment
      of patients with acute hepatic failure.

PMID- 8733281
TI  - [Mammary phyllodes tumor. A clinico-pathological review of 14 cases].
AB  - We report a retrospective analysis of 14 female patients, aged 20 to 62 years
      old, with phyllodes tumors of the breast. The tumors were located in the right
      breast in nine patients and their diameter ranged from 2.5 to 28 cm. Six
      mammographies and six needle cytological examinations were performed and aided
      very little to the diagnosis. The preoperative diagnosis was correct in five
      patients and the principal differential diagnosis was fibroadenoma. Eight
      patients were subjected to tumorectomy, three to simple mastectomy, one to a
      cleaning mastectomy, one to a modified radical mastectomy and one to a
      subcutaneous mastectomy. The anatomopathologic study disclosed an increased
      stromal growth in two patients and increased stromal cellularity in six cases.
      Only one case had more than five mitoses per microscopic field. Phyllodes tumors
      are infrequent, their diagnosis requires a high degree of clinical suspicion and
      they have a benign biologic behaviour.

PMID- 8733282
TI  - [Histopathological study of minor salivary glands in alcoholics].
AB  - A qualitative and quantitative histological analysis of minor salivary glands was
      carried out in 60 alcoholics and 20 matched control patients. Minor salivary
      glands biopsies were obtained and samples were processed for conventional light
      microscopy. A quantitative morphometrical assessment was carried out by counting
      the number of acinar cells present in an area by means of a squared grid eye
      piece. Neither hipertrophic nor atrophic responses were found in the quantitative
      analysis. Histological changes such as acinar degeneration, hyperemia,
      mononuclear inflammatory and fat infiltration were found in both experimental and
      control samples. None of these findings reached statistical significance. Eleven
      adult alcoholics without liver damage (ASD) presented duct dilatation. On the
      other hand, only 3 adult alcoholics with liver damage (ACD) developed this
      response. This difference was statistically significant (p = 0.02). Perhaps no
      difference was found when we compared ASD group with its respective control group
      (p = 0.699). We could not differentiate if this change was due to alcoholism or
      another undeterminated factor. At least under the scope of this study, we may
      conclude that minor salivary glands are scarcely affected by alcoholism even when
      liver damage has been established.

PMID- 8733283
TI  - [In vitro comparative activity (E test) of sparfloxacin and other 8 antimicrobial
      agents against bacteria isolated from patients with respiratory infections
      acquired in the community].
AB  - Sparfloxacin is a new antimicrobial that, while maintaining a good activity
      against gram negative bacilli, has a better in vitro activity against gram
      positive bacteria such as S pneumoniae, intracellular pathogens and anaerobic
      bacteria. The aim of this work was to study the in vitro activity of sparfloxacin
      against bacteria isolated from patients with community acquired respiratory
      infections between October 1994 and January 1995. Using the E-test technique, we
      studied the susceptibility to sparfloxacin, ciprofloxacin, ampicillin,
      amoxicillin/clavulanic acid, cefuroxime, cefotaxime, erythromycin, methicillin
      and nalidixic acid of 50 strains of S pneumoniae, 50 strains of H. influenzae, 50
      strains of S aureus and 50 strains of S pyogenes. Sparfloxacin was active against
      100% of S pneumoniae, H influenzae and S pyogenes strains. Twenty two percent of
      S aureus strains were resistant and the MIC 90 was 12 micrograms/ml. Sparfloxacin
      showed the best in vitro activity against H influenzae and S aureus, a similar
      activity with ampicillin and cefotaxime against S pneumoniae and a similar
      activity with ampicillin but superior to all other studied antimicrobial against
      S pyogenes. It is concluded that sparfloxacin is a good antimicrobial for
      bacteria isolated from patients with respiratory infections.

PMID- 8733284
TI  - [Thyroid nodule in Basedow-Graves disease and thyroid cancer: experience in 6
      patients].
AB  - Traditionally, Basedow-Graves disease was considered a protection against thyroid
      cancer. However, recent reports suggest that cancer occurs with a higher
      frequency than expected and is more aggressive in this disease. We report six
      patients with hyperthyroidism due to a Basedow Graves disease that presented a
      palpable thyroid nodule, which was cold in the scintiscan and solid in the
      ultrasound examination. Fine needle cytology disclosed cancer in five cases (two
      with cytological features of greater aggressiveness) and a nodular hyperplasia in
      one. The diagnosis was confirmed in the surgical piece in all patients. We
      conclude that Basedow-Graves disease and thyroid cancer, which can have an
      increased aggressiveness, may coexist.

PMID- 8733285
TI  - [Delusional disorders with delirium of somatic type].
AB  - The delusional disturbance is characterized by the presence of persistent
      delusions that are not bizarre, which cannot be attributed to schizophrenia, mood
      state disorders, substance abuse or organic brain disease. We report a 37 years
      old male that presented the disease during the last seven years and had very
      little response to a two months course of pimozide, a neuroleptic whose
      effectiveness in this disease has been suggested.

PMID- 8733286
TI  - [Variability of the heart rate: its physiopathological basis and its use as
      prognostic index after acute myocardial infarction].
AB  - The analysis of heart rate variability studies the normal oscillatory changes of
      the cardiac cycle. These changes are periodical or incidental and are controlled
      by humoral, sympathetic and parasympathetic stimuli. Frequency domain and time
      domain are the methods most used to assess heart rate variability. Time domain
      analyses variations of cardiac cycle using the standard deviation of RR intervals
      in 24 hours (SDRR) and the percentage of difference between adjacent normal RR
      intervals of more than 50 ms (pNN50). Frequency domain, converts beat to beat
      fluctuation of heart rate into different components of frequency by a fast
      Fourier transformation. They are classified, according to their magnitude, in
      high frequency (> 0.15 Hz), low frequency (0.04-0.15 Hz), very low frequency
      (0.003-0.04 Hz) and extremely low frequency (< 0.003 Hz). The high frequency
      fluctuations are predominantly related to parasympathetic activity whereas the
      low frequency fluctuations are related to sympathetic and parasympathetic
      activity. The physiology of very low and extremely low frequency fluctuations
      remains unclear. Many reports have shown that a decrease in heart rate
      variability after myocardial infarction may independently identify patients at
      risk for sudden death. However, the physiopathologic basis of these findings is
      not yet elucidated.

PMID- 8733287
TI  - [In the search of a language for medical ethics].
AB  - After World War II, the interest in medical ethics increased and several
      international codes defending patients rights appeared. Four pragmatic, non
      ideological and non religious principles were defined to analyze clinical ethical
      problems. Autonomy, the capacity of self management and to reach our own informed
      decisions; the informed consent is the way to accomplish this principle.
      Beneficence, the basic principle of medical acts, with the risk of being
      transformed in an extreme paternalism. A reinterpretation of beneficence
      equilibrates the rights of patients physicians. Non wickedness, first of all not
      to harm, a Hippocratic idea to prevent iatrogenesis and Justice, to maintain
      personal, social and political equity. These principles are a language, an
      ethical analysis methodology and give clues for our relationship with patients.
      They are a guide for personal analysis, reflection and change and show a
      collective and individual path to incorporate ethics to our daily work.

PMID- 8733288
TI  - [Genes of negroid origin in the urban population of Santiago].

PMID- 8733289
TI  - [Gallbladder cancer].

PMID- 8733290
TI  - [Epidemiological profile of liver cirrhosis in Chile 1970-1992].
AB  - BACKGROUND: Liver cirrhosis is an important public health problem in Chile. AIM:
      To review the main epidemiological features of liver cirrhosis in Chile in the
      last 22 years. METHODS: Review of yearbooks of mortality and causes of death of
      the Ministry of Health and Instituto Nacional de Estadisticas, review of hospital
      discharges and review of international statistics published by the World Health
      Organization. RESULTS: The mortality rate of liver cirrhosis in 1992 was
      17.9/100,000 inhabitants and represented 3.3% of all deaths. The risk of
      cirrhosis is higher among men and in people over 64 years of age. In the last
      decade, death rates of young adults (15-44 years old) and children decreased
      dramatically. Hospital discharge rates for cirrhosis have decreased from 46.7 in
      1970 to 40.4 in 1992. The men/women ratio in 1991 was 2.1/1 for hospital
      discharges and 2.8/1 for mortality. Mortality was higher in large urban areas
      (Santiago, Valparaiso and Concepcion). A correlation of +0.17 was found between
      death rates for cirrhosis and wine production per capita. CONCLUSIONS: Cirrhosis
      continues to be a highly prevalent disease in Chile.

PMID- 8733291
TI  - Sprouting of A beta fibers into lamina II of the rat dorsal horn in peripheral
      neuropathy.
AB  - Cholera toxin beta-subunit conjugated to horseradish peroxidase was used to label
      the large myelinated (A beta) fiber input to the dorsal horn in a model of
      peripheral neuropathy induced by tight ligation of the L5 and L6 spinal nerves.
      Following induction of neuropathy, A beta fibers were present in lamina II of the
      ipsilateral dorsal horn, a region normally devoid of A beta input. This
      reorganization of large fiber input to the superficial dorsal horn provides some
      anatomical basis for sensory changes found in this model of neuropathic pain.

PMID- 8733292
TI  - Voltage-activated fast currents of frog optic tectum neurones are blocked by
      ouabain or K(+)-free solution.
AB  - Frog optic tectum neurones in vitro (under whole cell patch clamp with a Cs(+)
      filled electrode) generated, in response to voltage steps negative to -80 mV from
      -60 mV holding potential, transient inward currents dependent on extracellular
      Na+ and blocked by tetrodotoxin (TTX). Depolarizing steps from the same holding
      potential induced conventional, fast Na+ currents followed by a transient outward
      cationic current (Icat). Voltage-activated Na+ currents (induced by negative or
      positive steps) and Icat were blocked by ouabain or K(+)-free solution with
      comparable timecourse. It is suggested that transient inward and outward currents
      of frog tectal neurones were at least partly dependent on the rapid operation of
      a membrane cation transporter.

PMID- 8733293
TI  - Inhibition of nitric oxide synthase or cyclo-oxygenase pathways in organum
      vasculosum laminae terminalis attenuates interleukin-1 beta fever in rabbits.
AB  - Fever was induced in rabbits by i.v. administration of lipopolysaccharide (LPS)
      or administration of interleukin-1 beta (IL-1 beta) into the organum vasculosum
      laminae terminalis (OVLT). Intra-OVLT injection of IL-1 receptor antagonist (IL
      lra), 1 h before LPS or IL-1 beta injection, inhibited the LPS- or IL-1 beta
      induced fever. Dexamethasone (a potent inhibitor of the transcription of
      inducible nitric oxide synthase, iNOS), L-N5-(1-iminoethyl)ornithine (an
      irreversible NOS inhibitor), aminoguanidine (a specific iNOS inhibitor), or
      indomethacin (an inhibitor of cyclo-oxygenase, COX) also inhibited IL-1 beta
      induced fever when injected into the OVLT 1 h before IL-1 beta injection. These
      results suggest that iNOS or COX pathways in the OVLT mediate the IL-1 beta
      induced fever in rabbits.

PMID- 8733294
TI  - Systemic and intrastriatal theophylline have opposite effects on dopamine and
      dopamine metabolites measured by intrastriatal microdialysis in the rat.
AB  - Using a model of intrastriatal microdialysis, we studied the effect of
      theophylline, an A1 and A2A adenosine receptor antagonist on striatal dopamine
      (DA) and DA metabolites. Systemic administration of theophylline (10 and 50
      mg/kg) significantly reduced striatal extracellular (EC) levels of DA and its
      metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxy
      phenylacetic acid (HVA). Intrastriatal administration of theophylline (10(-2) M)
      significantly increased DA and its metabolites (DA1 + 120%; DOPAC, +28%; HVA,
      +30%). Contradictory effects of systemic and intrastriatal theophylline point to
      theophylline interactions with different receptors possibly at different
      locations.

PMID- 8733295
TI  - Apoptosis is induced in the subependyma of young adult rats by ionizing
      irradiation.
AB  - To determine if radiation-induced apoptosis occurred in young adult brain, we
      exposed 2-3-month old rats to single x-ray doses of 5 or 30 Gy. Apoptosis was
      quantified using the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method
      and a morphologic assessment of nuclear fragmentation. Apoptosis occurred
      primarily in the subependyma but also in the corpus callosum, peaking 6 h after
      irradiation. At 48 h there were no apoptotic nuclei observed. These data are the
      first to show that apoptosis occurs in the young adult rat brain after ionizing
      irradiation. Further studies are required to define the particular cell type(s)
      involved and to address the role of this process in the pathogenesis of late
      radiation injury.

PMID- 8733296
TI  - Pancreastatin-like immunoreactivity in globular dystrophic neurites of senile
      plaques in brains of patients with Alzheimer's disease.
AB  - The immunohistochemical localization of pancreastatin (PST) was examined in
      brains of Alzheimer's disease (AD) and control cases using three different
      antisera to PST, and was compared with the staining for chromogranin A (CgA), the
      precursor of PST. In control brains, CgA-like immunoreactivity was observed in
      the cytoplasm and fibers of certain neuronal populations, which were not
      immunostained with any of the PST antisera. In AD brains, dystrophic neurites of
      globular shape located in senile plaques were immunostained with each of the PST
      antisera, as well as with the CgA antibody. PST-positive and CgA-positive
      dystrophic neurites showed similar profiles. The present study indicates that CgA
      is probably cleaved to produce PST in some globular dystrophic neurites in senile
      plaques.

PMID- 8733297
TI  - Expression of cathepsin D during the progression of human gliomas.
AB  - Recent studies suggest that aspartic proteinase cathepsin D may be implicated in
      tumor invasion and metastasis either directly by degrading extracellular matrix
      or indirectly by activating the cysteine proteinases such as procathepsin B, H,
      and L to mature forms or by inactivating cysteine proteinase inhibitors. In this
      study we determined for the first time whether increased levels of cathepsin D
      correlate with glioma progression by enzymatic assay, ELISA, and western
      blotting. Cathepsin D activity and content were higher in anaplastic astrocytoma
      and in glioblastoma tissue extracts especially when compared to normal brain
      tissue and low-grade gliomas. There was a significantly increased intensity of an
      M(r) 29,000 band in glioblastoma and anaplastic astrocytoma compared to low-grade
      glioma and normal brain tissue on Western blotting analysis using its specific
      antibodies. Cathepsin D antibody inhibited the invasion of glioblastoma cell
      lines in a dose-dependent manner. These results suggest that the expression of
      cathepsin D is dramatically upregulated in malignant gliomas, and that its
      increase correlates with the malignant progression of human gliomas in vivo.

PMID- 8733298
TI  - Localization of AMPA glutamate receptor subunits in subpopulations of non
      pyramidal neurons in the rat basolateral amygdala.
AB  - A two-color immunoperoxidase technique was used to investigate the localization
      of GluR1 and GluR2/3 alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) glutamate
      receptor subunits in subpopulations of non-pyramidal neurons in the rat
      basolateral amygdala. Antibodies to neuropeptide Y (NPY), vasoactive intestinal
      peptide (VIP), and calcium binding proteins were used to mark three distinct
      subsets of non-pyramidal cells. Only non-pyramidal neurons containing the calcium
      binding proteins parvalbumin (PV) and calbindin D-28k (CB) exhibited robust GluR1
      like immunoreactivity (GluR1-ir). Light GluR1-ir was observed in some neurons
      with NPY-ir and VIP-ir, as well as in some pyramidal cells. Only pyramidal cells
      exhibited robust GluR2/3-ir. No significant amount of GluR2/3-ir was seen in any
      of the three main classes of non-pyramidal cells. These findings indicate that in
      the rat basolateral amygdala GluR2/3-ir is found primarily in pyramidal neurons
      whereas GluR1-ir is found mainly in non-pyramidal neurons that contain PV or CB.

PMID- 8733299
TI  - NADPH-diaphorase histochemistry of rat choroid plexus blood vessels and
      epithelium.
AB  - Choroid plexus is the major source of cerebrospinal fluid. The hemodynamics and
      secretory function of this tissue are controlled by multiple endocrine and neural
      mechanisms. Nitric oxide (NO) has been demonstrated to play an important role in
      regulating choroidal blood flow. In the present study, performed on adult male
      Sprague-Dawley rats, we employed a NADPH-diaphorase (NADPH-d) histochemical
      method to localize nitrergic innervation of choroidal blood vessels. This
      approach was based on previous observations that NADPH-d colocalizes with NO
      synthase, a synthetic enzyme for NO, in the central and peripheral nervous
      systems. NADPH-d-positive nerve fibers were found to accompany both large
      arteries and veins and blood microvessels (possibly arterioles) located in
      choroidal stroma. NADPH-d reaction product was also localized to the vascular
      endothelial lining and choroidal epithelial cells. All the above sources of NO
      may play important roles in the regulation of secretory and hemodynamic functions
      of the choroid plexus.

PMID- 8733300
TI  - Effects of a prepulse stimulus on the masseteric inhibitory reflex in humans.
AB  - We investigated the effects of a weak cutaneous stimulus applied to the digital
      nerves (prepulse) on the masseter inhibitory reflex (MIR) to electrical
      stimulation of the mental nerve in nine healthy volunteers. The prepulse
      stimulus, which had no direct effect on the masseter muscle EMG activity, induced
      a significant decrement in the area of the second phase of the MIR at
      interstimulus intervals between 50 and 100 ms. The percentage reduction induced
      on the inhibitory phase of the MIR was not different from that induced by the
      same prepulse on the late excitatory phase (R2) of the orbicularis oculi muscle
      to supraorbital nerve electrical stimulation during voluntary contraction. The
      effects observed during contraction were significantly less marked than those
      observed in the blink reflex at rest. We conclude that prepulse inhibition occurs
      in various brainstem reflexes, is similarly active on excitatory and inhibitory
      responses, and is reduced during voluntary activation.

PMID- 8733301
TI  - Enhancement of human motor cortex inhibition by the dopamine receptor agonist
      pergolide: evidence from transcranial magnetic stimulation.
AB  - Focal transcranial magnetic stimulation was used to evaluate the effect a single
      oral dose (0.125 mg) of the dopamine agonist pergolide on the excitability of the
      motor cortex in five healthy subjects. Resting and active motor thresholds of the
      abductor digiti minimi muscle were unaffected. The mean duration of the cortical
      silent period was significantly lengthened by up to 22 ms. The cortico-cortical
      inhibition as studied by a paired conditioning-test stimulation (interstimulus
      intervals of 1-5 ms) was enhanced significantly while the cortico-cortical
      facilitation at longer intervals (6-15 ms) showed only an insignificant trend
      towards less facilitation. All effects peaked at 3 h after drug intake and were
      reversible after 24 h. Peripheral motor excitability as tested by the duration of
      the peripheral silent period and the size of the maximum M wave remained
      unchanged. The present data support the view that pergolide is capable of
      enhancing motor cortex inhibition which is known to be deficient in idiopathic
      Parkinson's disease.

PMID- 8733302
TI  - Pain due to tissue acidosis: a mechanism for inflammatory and ischemic myalgia?
AB  - To study the role of protons in ischemic muscle pain we employed the "submaximal
      effort tourniquet technique' and, in a second attempt, an intramuscular pressure
      infusion of acid phosphate buffer. The pH measured in the forearm skin covering
      the muscles at work during the tourniquet test continuously dropped to a mean
      value of pH 7.00 +/- 0.26, starting 1 min after the contractions, while the pain
      increased in direct correlation with the hydrogen ion concentration (r = 0.96).
      After restoring the blood supply, the intradermal proton concentration decreased
      more slowly than the muscular pain. The same subjective quality of deep muscular
      pain was achieved with pressure infusion of acid phosphate buffer (pH 5.2) into
      the forearm muscles. Constant flow rates evoked constant, apparently non-adapting
      magnitudes of pain with a log-linear stimulus-response relationship (r = 0.93).
      Changes in flow rate were followed by changes in pain ratings with a certain
      phase lag. We conclude that muscular pain induced by infusion of acidic phosphate
      buffer and pain from ischemic contractions are generated through the same
      mechanisms based on the algogenic action of protons.

PMID- 8733303
TI  - Three different mutations of presenilin 1 gene in early-onset Alzheimer's disease
      families.
AB  - Presenilin-1 (PS-1) gene of three Japanese pedigrees with early-onset familial
      Alzheimer's disease (FAD) disclosed two novel missense mutations resulting in
      Val96Phe and Ile213Thr, and one mutation resulting in His163Arg. The mean age at
      onset in a family with His163Arg mutation was similar to those reported in other
      families with His163Arg. Our results suggested the existence of a variety of PS-1
      mutations, and that early-onset FAD with PS-1 mutations is highly penetrant and
      is only rarely subject to modulation by genetic or environmental modifying
      factors.

PMID- 8733304
TI  - Mechanically evoked cerebral potentials to sudden ankle dorsiflexion in human
      subjects during standing.
AB  - Mechanically evoked cerebral potentials (MECP) were studied in humans standing on
      a movable platform with three different stance widths. A sudden platform tilt of
      4 degrees produced ankle dorsiflexion and resulted in scalp potentials of five
      distinct components, the earliest being a positive deflection at 35/60 ms. Their
      latencies have shown fairly consistent values among the three stance widths,
      while the amplitudes underwent some significant changes under the wide stance
      condition as compared with tightly close feet. These findings were interpreted as
      purporting evidence of altered somaesthetic afferent input from lower limbs
      during standing with widely apart support surface.

PMID- 8733305
TI  - The role of 5HT3 in nociceptive processing in the rat spinal cord: results from
      behavioural and electrophysiological studies.
AB  - Recent studies have suggested that activity at different 5HT receptor subtypes in
      the spinal cord either inhibits or facilitates nociceptive processing in the
      spinal cord. The present study has examined the role of 5HT3 receptors in
      nociceptive processing in the dorsal horn of the rat spinal cord. Using both
      behavioural and electrophysiological studies, 5HT3 ligands have been applied by a
      common route (i.e. intrathecal microinjection). In addition, only noxious heat
      has been used as a form of stimulation. Intrathecal injection of mCPBG (0.02-0.2
      nmol) increased the responsiveness of dorsal horn neurones to noxious
      stimulation. In contrast, two 5HT3 antagonists (ICS 205-930 (0.015-0.15 nmol) and
      GR 380032F (ondansetron 34 nmol)) reduced nociceptive responses. Using doses
      which influenced nociceptive neuronal responses no significant change in TFL was
      recorded. These findings suggest that activation at 5HT3 receptor facilitates
      nociceptive responses of some dorsal horn neurones; these results are discussed
      in relation to earlier reports concerning alternative effects.

PMID- 8733306
TI  - Developmental changes in endothelin A and endothelin B receptor subtypes in
      embryonic chick brains.
AB  - The kD and Bmax values for [125I]endothelin-1 ([125I]ET-1) binding to the brain
      membrane preparations of 3- to 20-day-old chick embryos were compared. The kD
      values differed only slightly during development. In contrast, the Bmax values
      varied six-fold during the embryonic stages examined and displayed two distinct
      peaks, on day 5 (204 +/- 13 fmol/mg protein, n = 3) and day 13 (110 +/- 4 fmol/mg
      protein, n = 7) of incubation. Displacement of [125I]ET-1 binding to 5- and 13
      day-old embryonic brain membrane preparations was carried out using ET-3 and BQ
      123, a selective ETA receptor antagonist, as competing ligands. The results
      suggest that the ETA receptor subtype is primarily synthesized at the beginning
      of development followed by the production of non-selective ETB receptor subtype
      at a later time.

PMID- 8733307
TI  - Muscarinic cholinergic receptor subtypes in human peripheral blood lymphocytes.
AB  - The subtypes of muscarinic cholinergic receptors were studied in human peripheral
      blood lymphocytes with radioligand binding techniques and the non-selective
      muscarinic cholinergic receptor antagonist [3H]quinuclidinyl benzylate (QNB) as a
      ligand. [3H]QNB was bound to human peripheral lymphocytes in a manner consistent
      with the labelling of muscarinic cholinergic receptors. The dissociation constant
      (Kd) value was 0.60 +/- 0.08 nM and the maximum density of binding sites (Bmax)
      was 2.33 +/- 0.03 fmol/2.2 x 10(6) cells. The binding was time-, temperature- and
      concentration-dependent, belonging to a single class of high affinity sites.
      Analysis of the pharmacological profile of [3H]QNB binding in the presence of
      compounds specific for the different muscarinic receptor subtypes suggests that
      human peripheral blood lymphocytes express mainly muscarinic cholinergic M2 and
      M3 receptor subtypes and to a lesser extent muscarinic M4 receptors. The
      characterization of the subtypes of muscarinic cholinergic recognition sites
      expressed by human peripheral blood lymphocytes may represent a tool for
      investigating the possible relationships between immune and cholinergic systems
      in normal and pathologic conditions.

PMID- 8733308
TI  - The effect of tetraethylammonium on intracellular calcium concentration in
      Alzheimer's disease fibroblasts with APP, S182 and E5-1 missense mutations.
AB  - It has been proposed that the lack of intracellular calcium concentration
      ([Ca2+]i) increase induced by the potassium channel blocker tetraethylammonium
      (TEA) in skin fibroblast cell lines identifies patients with both sporadic and
      familial Alzheimer's disease (AD). In order to verify this hypothesis, the effect
      of TEA on [Ca2+]i was studied in single fura-2-loaded skin fibroblast cell lines
      available in the Tissue Bank of the Italian Research Council. Four out of eight
      familial AD patients (one patient with S182 mutation, one patient with E5-1
      mutation and two patients with 717 Val-->Ile APP mutation) and two out of five
      sporadic AD patients showed a positive response to TEA, whereas five out of 11
      control lines were unresponsive. Our data suggest that the absence of the TEA
      induced increase in [Ca2+]i in skin fibroblast cell lines does not identify all
      AD patients.

PMID- 8733309
TI  - [Progression of viral infection in twins born from a mother infected with human
      immunodeficiency virus].
AB  - We studied the evolution of HIV-1 infection and immune response during six years
      in two twins born from an infected mother. The children had a continuous
      progression of the infection, proved by CD4+ cell count, serum anti-HIV
      antibodies, cultivable virus and proviral load. Now, both children are on
      antiviral treatment. The analysis of serum antibodies showed a different immune
      response in both children. One of them developed higher levels of antibodies
      directed against viral proteins and synthetic peptides derived from their
      aminoacid sequence. In this child, the amount of cultivable virus increased less
      than in his twin. Nucleotide sequencing of a part of viral genoma, showed that
      the virus belonged to the B subtype, prevalent in America and Europe. The
      observed differences in viral sequences suggest a different selective pressure in
      both twins. This phenomenon could be related to the observed differences in
      immune response.

PMID- 8733310
TI  - [Immunologic and insulin secretion markers in non insulin dependent diabetic
      patients with secondary failure to oral hypoglycemic drugs].
AB  - BACKGROUND: The pathogenesis of secondary failure to hypoglycemic agents is
      heterogeneous. Some patients are true insulin dependent diabetics with a slow
      autoimmune disease suggested by their positive islet cell antibodies. Others,
      have an increased insulin resistance. AIM: To assess the frequency of positive
      islet cell antibodies in diabetic patients with secondary failure to oral
      hypoglycemic agents. PATIENTS AND METHODS: Thirty one diabetics, 16 with recent
      (less than six months) secondary failure and 15 with metabolically stable non
      insulin dependent diabetes were studied. All patients were older than 25 years
      old and had a body mass index of less than 30 kg/m2. C peptide levels before and
      at 5, 15 and 30 min after IV glucagon, islet cell antibodies using the Poly Human
      IgG peroxidase method and insulin sensitivity and secretion (estimated by the
      Homeostasis Model Assessment) were measured. RESULTS: Patients with secondary
      failure had lower C peptide levels, compared to subjects with stable diabetes
      (basal: 1.5 +/- 0.2 and 2.8 +/- 0.2 ng/ml; 5 min: 2.4 +/- 0.3 and 5.5 +/- 0.5
      ng/ml; 15 min: 1.9 +/- 0.3 and 4.0 +/- 0.6 ng/ml; 30 min: 1.6 +/- 0.3 and 3.4 +/-
      0.5 ng/ml). Beta cell activity was 20.6 +/- 4.3% in patients with secondary
      failure and 92.2 +/- 9% in stable diabetics (p < 0.01). Insulin sensitivity was
      similar in both groups (48.6 +/- 6 and 42.8 +/- 3.5% respectively). Three
      patients with secondary failure and none with stable diabetes had positive islet
      cell antibodies. When comparing patients with secondary failure and positive
      antibodies and subjects with secondary failure and negative antibodies, the
      former had non significantly lower age, BMI and C peptide levels. CONCLUSIONS:
      Some diabetic patients with secondary failure have positive islet cell
      antibodies. They should be measured in these patients to start insulin treatment
      precociously.

PMID- 8733311
TI  - [Genetic predisposition to develop insulin-dependent diabetes mellitus. A
      population study in Santiago and Temuco, Chile].
AB  - Insulin-dependent diabetes mellitus (IDDM) is strongly associated with particular
      HLA-DQ alpha/beta markers in white population. The heterodimers conformation
      composed of a DQ alpha chain with an arginine at residue 52 (Arg52) combined to a
      DQ beta chain lacking an aspartic acid at residue 57 (non Asp57) increase
      markedly the risk to develop IDDM. To confirm this association, 63 IDDM patients
      from Santiago de Chile registry, 20 IDDM patients from Temuco registry and 74
      unrelated healthy non diabetic control subjects were studied. With polymerase
      chain reaction (PCR) and sequence specific oligonucleotide probes the individuals
      were typed for their HLA-DQA1 and DQB1 alleles, their DQA1/DQB1 genotype and
      heterodimers conformation were compared. In diabetic population both markers
      Arg52 homocygote and non Asp57 homocygote were markedly increased regard to
      control subjects (R/R: 0.76 and 0.85 vs 0.33; ND/ND: 0.78 and 0.75 vs 0.50, p <
      0.05). A high relative risk (RR) was determined for both homocygote markers in
      IDDM groups. Arg52 DQ alpha (R)/non Asp57 DQ beta (ND) heterodimers were strongly
      associated with susceptibility to IDDM. A high RR was observed in patients with
      four susceptibility DQ heterodimers (RR1: 13.7 in IDDM-Santiago and RR2: 18.6 in
      IDDM-Temuco, p < 0.00003). The HLA-DQ alpha/beta markers and their risk
      heterodimers are increased in our diabetic population and could be considered as
      susceptibility markers to develop IDDM.

PMID- 8733312
TI  - [Infection and reactive arthritis: clinico-bacteriological correlation in
      seronegative arthropathies].
AB  - The aim of this study was to search infections that trigger reactive arthritis.
      Eighty-six patients with seronegative arthritis (SNA) were studied; 32 had
      reactive arthritis, 21 ankylosing spondylitis, 7 psoriatic arthritis and 26
      undifferentiated seronegative oligoarthritis. As controls, 70 patients with
      connective tissue diseases (CTD) and 55 healthy volunteers (HV) were studied.
      Serological evidence for infection with Chlamydia trachomatis was studied with
      micro immunofluorescence, looking for L2 and BED serotypes and serological
      evidence for Yersinia infection, using a commercial kit. Stool cultures were done
      in seven patients with recent diarrhea, and endourethral or endocervical cultures
      in 35 individuals. Serotypes L2 or BED were positive in 23 of 83 patients with
      SNA, 3 of 39 patients with CTD and 4 of 55 HV (p < 0.03). IgG class antibodies
      against L2 were detected in 17% of SNA patients, 2.6% of CTD patients and 5.4% of
      HV (p < 0.05). IgM class antibodies were detected in 6 SNA patients, 0 CTD
      patients and 2 HV (NS). Twelve of 35 cultures were positive for Chlamydia. As a
      whole 30% of SNA patients has serological or bacteriological evidence for
      Chlamydia infection. Serology for Yersinia was positive in 39 of 81 SNA patients,
      1 of 54 CTD patients and 3 of 51 HV (p < 0.01). Rates of infections were similar
      among male, female, HLA B27 positive and HLA negative subjects. It is concluded
      that SNA patients have a high prevalence of infections by Chlamydia trachomatis
      or Yersinia enterocolitica.

PMID- 8733313
TI  - [Patients with chronic airflow limitation: effects of the inspiratory muscle
      training with threshold load valve, built with appropriate technology, associated
      to nutritional support].
AB  - AIM: To assess prospectively the effects of a controlled program of inspiratory
      muscle training program and nutritional support in patients with chronic
      obstructive lung disease (COPD). PATIENTS AND METHODS: Twenty-three patients with
      COPD were randomly assigned into four groups. Group I received a 1000 kcal/day
      nutritional supplement, given as a casein based enteral nutritional formula;
      group III was subjected to inspiratory muscle training, using an inexpensive
      pressure threshold load valve constructed according to the Appropriate Technology
      principles of the WHO, adjusted at 30% of Maximal Inspiratory Mouth Pressure and
      received also the nutritional supplement; group IV was trained but did not
      receive the nutritional supplement and group II was not trained nor supplemented.
      Patients were studied during three months and monthly, inspiratory muscle
      function, exercise capacity and anthropometry were measured. RESULTS: A
      significant improvement in exercise capacity, maximal inspiratory pressure and
      inspiratory muscle endurance was observed in the four groups throughout the
      study. Trained subjects had greater improvement in their inspiratory muscle
      endurance, compared to untrained subjects. Nutritional support had no effect in
      inspiratory muscle function or exercise capacity. No changes in anthropometric
      measures were observed. CONCLUSIONS: The pressure threshold load valve used in
      this study, improved inspiratory muscle endurance and nutritional support had no
      effect in patients with COPD.

PMID- 8733314
TI  - [Hematological serological valves, and organ weight in adult Sprague-Dawley
      rats].
AB  - Sprague-Dawley rats are frequently used in experiments and their normal
      hematological, serologic and anatomical parameters are not easily available. The
      aim of this study was to measure these parameters in adult Sprague-Dawley rats.
      Twenty-four rats (12 males) whose weight ranged between 200 and 300 g, raised at
      the Instituto de Salud Publica in controlled environmental conditions and fed
      with pellets were studied. After a 24 h fast, animals were anesthetized with
      Droperidol and Ketamine, and after obtaining a cardiac blood sample, sacrificed
      by exsanguination. Most organs were withdrawn and weighed. Mean values for blood
      glucose, calcium, amylase, total proteins, cholesterol, AST, ALT, bilirubin,
      alkaline phosphatases, electrolytes and complete blood count were determined.
      Heart, lung, pancreas, kidney and testicle mean weight was also calculated. Male
      and female rats had significant differences in packed red cell volume, white
      blood cell count and hemoglobin.

PMID- 8733315
TI  - [Who finances medical research in Chile?].
AB  - To identify those institutions granting medical research in Chile, every issue of
      Revista Medica de Chile published between 1987 and 1994 was reviewed, under the
      assumption that a vast majority (over 70%) of papers released by Chilean authors
      in topics of internal medicine and related subspecialties would have been
      submitted for publication in this journal. This assumption was based in the solid
      prestige of Revista Medica de Chile among Chilean physicians and investigators:
      it is one of the oldest medical journals in the world (founded in 1872) and its
      inclusion in the most important international indexes (e.g. Index Medicus,
      Current Contents) qualifies it in the "mainstream literature". Papers classified
      as "Original Articles", "Clinical Experiences", "Review Articles", "Public
      Health", "Case Reports", "Clinical Laboratory", "Special Articles" and "Medical
      Education" were screened for acknowledgment of financial support beyond the
      resources needed for routine clinical work. Among 1,528 manuscripts published,
      344 were "Original Articles" and 61.3% of them acknowledged special financial
      support. Five hundred and one manuscripts were "Clinical Experiences" and 21.5%
      of them received special financial support; similar proportions were detected in
      "Review Articles" and "Public Health" topics. The institution ranked as providing
      support most often was the "Fondo Nacional de Ciencias y Tecnologia" (FONDECYT),
      a governmental fund that assigns resources to research in all areas of science
      and technology through a peer-reviewed nationwide annual contest. FONDECYT was
      identified as provider of financial support to 45.2% of the "Original Articles"
      and "Clinical Experiences"; Chilean universities were mentioned by 33.6% and
      other entities (including pharmaceutical companies, other national and foreign
      organizations) by 23.1%. The University of Chile was the main Chilean university
      mentioned in the acknowledgments. The proportion of papers receiving special
      financial support was lower in Revista Medica de Chile than in three leading
      journals from developed countries (70% of Articles published in Annals of
      Internal Medicine, 74% in Lancet and 78% in The New England Journal of Medicine)
      but this proportion has been steadily increasing since 1987. The increase has
      been due only to FONDECYT and it would be unreasonable to expect that this
      institution will maintain such an expansion indefinitely. Therefore, Chilean
      investigators should attract more resources from the universities, the
      pharmaceutical companies and other non-governmental institutions.

PMID- 8733316
TI  - [Comparison between digoxin and atenolol in chronic atrial fibrillation].
AB  - The benefits of digoxin in patients with atrial fibrillation may be reduced due
      to its limited effect on atrioventricular conduction. The aim of this work was to
      compare digoxin and atenolol on functional class, resting and exercise heart rate
      and exercise capacity in patients with atrial fibrillation. Thirteen subjects
      with this condition, normal echocardiographic left ventricular function and size,
      a resting heart rate less than 80 beats/min and with no contraindication for beta
      blocker or digoxin use were studied. Patients were randomly assigned to receive
      initially digoxin 0.25 mg o.d. or atenolol 100 mg o.d. in a double blind fashion.
      The doses were adjusted to obtain a heart rate between 60 and 80 beats/min at the
      end of the first week of treatment. After two weeks of treatment, outcomes were
      assessed, patients were left without treatment for one week and crossed over to
      the other drug after that. Resting heart rates achieved with digoxin and atenolol
      were similar (67 +/- 11 and 65 +/- 23 beats/min respectively). However, maximal
      exercise heart rates and maximal exercise time were higher during digoxin
      treatment (166 +/- 23 vs 135 +/- 27 beats/min and 9.95 +/- 1.68 vs 8.5 +/- 2 min
      respectively). NYHA functional class deteriorated in three patients receiving
      atenolol. We conclude that atenolol achieves a better control of heart rate
      during exercise but also reduces maximal exercise capacity.

PMID- 8733317
TI  - [Synovial chondromatosis: review of 25 monoarticular cases].
AB  - We report 25 patients (20 female) aged 34 to 74 years old, with monoarticular
      synovial chondromatosis. Affected joints were the knee in 25 cases, the ankle in
      one case and the elbow in one case. Chronic articular pain was the main symptom,
      followed by swelling, limitation in motion range, free palpable bodies and
      symptomatic popliteal cysts. X ray examination showed free calcified
      osteochondroid bodies in 48% of patients and secondary osteoarthritis in 36%.
      Bone scintiscan showed an increased focal uptake. All pathological samples had
      chondroid or osteochondroid nodules; 64% had small blood vessels, thickened with
      concentric collagen laminae and 20% had isolated chondrocytes. Malignant
      degeneration was not observed. Surgical or artroscopic synovectomy was the
      procedure of choice in 20 knees. In the affected elbow and ankle, extraction of
      free bodies was the sole procedure. No recurrences were observed. It is concluded
      that synovial chondromatosis must be considered in the differential diagnosis of
      chronic articular pain and monoarthritis.

PMID- 8733318
TI  - [Disseminated nocardiosis in 3 immunocompetent patients].
AB  - Nocardia asteroide infections, an aerobic actinomycete, have several forms and
      lungs, skin and brain are the organs most frequently involved. When the infection
      suspected, special staining methods must be ordered to identify the agent. We
      report three immunocompetent patients with disseminated nocardiosis, two
      presenting with nodular lesions of skin and lungs and one presenting with
      pulmonary involvement and brain abscesses. The importance of clinical suspicion
      and early diagnosis of nocardiosis is emphasized.

PMID- 8733319
TI  - [Breast cancer in males. Report of 4 cases].
AB  - Breast cancer is infrequent in men. We report four men with breast cancer seen at
      a surgical service in Valdivia. Their presentation form, histological diagnosis
      and evolution are described. An updated revision of the literature is also
      presented.

PMID- 8733320
TI  - [Extracorporeal membrane oxygenation in adult respiratory distress syndrome.
      Experience in 2 patients].
AB  - We report two female patients with adult respiratory distress syndrome and severe
      respiratory failure in whom extracorporeal membrane oxygenation was used. Its
      indication was due to a bad response to conventional treatment with mechanical
      ventilation and high levels of positive end expiratory pressure. A 2.0 or 2.2 m2
      membrane oxygenator in a veno-venous circuit with systemic anticoagulation was
      used, maintaining mechanical ventilation. In the first patient, the procedure was
      done early and was successful, increasing hemoglobin saturation from 39 to 87%.
      The patient was withdrawn from the procedure 48 hours later and died one week
      later due to a septic shock. The second patient was connected to the procedure
      after three weeks of respiratory distress syndrome and no increase in arterial
      oxygenation was achieved. The patient died due to an intracranial hemorrhage,
      probably hastened by systemic anticoagulation. The real benefits of
      extracorporeal membrane oxygenation are not defined yet.

PMID- 8733321
TI  - [Particpation of apoptosis in immunologic processes].
AB  - Apoptosis is a biological process that leads certain cells to die in a controlled
      fashion. Its biochemical manifestation is DNA fragmentation due to the action of
      an endonuclease and morphological consequence is the formation of apoptotic
      bodies, seen with light or electron microscopy. Apoptosis is universally
      important in embryogenesis and morphogenesis of all tissues. Lately, a
      fundamental role of apoptosis in the physiology and physiopathology of
      immunological events has been uncovered. This review details the role of
      apoptosis in the development of auto-tolerance, immunological memory and AIDS
      pathogenesis.

PMID- 8733322
TI  - [Does research make for better doctors?].

PMID- 8733323
TI  - [4 directions and a strategy for the foreseen changes in medical education].
AB  - The curricular renewal of Medical studies is a priority of the Faculty of
      Medicine of the University of Chile. After an initial phase of analysis done in
      1994, the process must be accomplished through the elaboration of proposals in
      1995-96 and their concretion in 1996-97. The new curriculum construction must be
      based, according to the Dean, on four general principles. First, the professional
      profile of the physician for the new century, mainly endowed with personal,
      scientific and technical conditions that allow him to deal with prevalent
      diseases not impairing the development of highly qualified specialities. Second,
      the health team, permitting the multidisciplinary work of other professions in
      health care and teaching activities. Third, an education based on how to learn
      rather than on what to learn, on academic autonomy of students and on flexibility
      of subjects. Fourth, curriculum and methodologies must be modified leading to
      active, responsible and updated learning.

PMID- 8733324
TI  - [Health inequalities: metropolitan region and southeast and west metropolitan
      health services].
AB  - Based on an inquiry that yielded national socioeconomic information, health
      inequalities among different quintiles of per capita income were explored in
      southeast and west health services of the metropolitan region. Inequalities were
      assessed establishing the type of health plan (state or private), occurrence of
      disease, access to medical attention and medications and use of health services.
      Fifty-eight percent of individuals living in the southeast health service and 74%
      of those living in the west health service had state funded health plans. This
      proportion was higher among subjects with lower earnings. One third of the
      population studied had a disease in the last three months. Ninety percent of
      these had medical attention. Most subjects that did not receive professional
      care, medicated them and felt that they did not require it. Subjects with lower
      earnings had greater difficulties to obtain medical attention or medications.
      Primary care comprises 62% of health actions and state funded sector is used by
      88% of subjects of subjects of the first quintile of per capita income.

PMID- 8733325
TI  - [On the reductionism of sciences].
AB  - The reduction of sciences to a limited number, in whose terms all scientific
      phenomena could be explained is conceivable. Particularly, is the reduction of
      biology to physics possible? The present article reviews critically this issue.
      First, it speaks about the topic on the parts and their relationships in the so
      called levels of organization. Secondly it refers to the reduction of one branch
      into another within a same science. Finally it analyses the arguments against the
      possibility of reducing biology to physics.

PMID- 8733326
TI  - [Professor Max Westenhofer (1871-1957) in Chile].
AB  - This work describes the activities of German anatomist Max Westenhofer during the
      different periods in which he resided in Chile (1908-1911; 1930-1932 and 1948
      1957). His contributions to pathology, the reasons for his resign from the
      University of Chile in 1911 and the main aspects of his hypothesis on the
      neotenic quality of human evolution are discussed.

PMID- 8733327
TI  - Hypertension in women--not to be overlooked.

PMID- 8733328
TI  - Accurate blood pressure measurement--is there a major problem?

PMID- 8733329
TI  - Efficacy of twice-daily amoxycillin/clavulanate ('Augmentin-Duo' 400/57) in mild
      to moderate lower respiratory tract infection in children.
AB  - A new amoxycillin/clavulanate regimen ('Augmentin-Duo' 400/57), to be given
      orally in two divided doses, has been proposed to overcome the inconvenience of
      tid dosing. This observer-blind, multicentre study randomised children aged two
      to 12 years with lower respiratory tract infection to seven days' treatment with
      either amoxycillin/clavulanate bid at a dose of 25/3.6mg/kg/day (221 patients) or
      the currently prescribed amoxycillin/clavulanate regimen of 20/5mg/kg/day tid
      (216 patients). Clinical success (cure) rates at follow up were 81.0% for the bid
      group and 77.8% for the tid group [difference 3.2%; 95% CI (-4.36, 10.80)],
      indicating that the regimens were of equivalent efficacy. Both regimens were well
      tolerated, and there was no statistically significant difference in the incidence
      of adverse experiences between the two groups. Compliance with study medication
      was high and similar for both groups (80% compliance: bid 90.0%; tid 87.0%).

PMID- 8733330
TI  - The psychological effects of breast screening in terms of patients' perceived
      health anxieties.
AB  - This study aimed to assess and compare the impact of letter of invitation,
      initial breast screening mammography, and subsequent recall procedures on the
      level of anxiety over breast problems. The survey of females undergoing routine
      breast screening procedures in a primary care setting is part of the first wave
      of a national breast screening programme in the UK. Women aged 50-64 registered
      with six general practices (n = 2618) were invited by letter to attend for
      screening. Their self-perceived impact of receipt of invitation letter,
      attendance at initial screening, and recall, in terms of anxiety and concern
      about breast problems, was measured by a self-report questionnaire and the
      physical, emotional and social dysfunction subscales of the Psychological
      Consequences of Screening Mammography Questionnaire (PCQ). Overall, subjects'
      anxiety levels diminished between the receipt of their invitation letter and the
      completion of their screening examination. Subjects did not, however, respond to
      the letter of invitation and screening procedure in a homogeneous manner. In a
      sample of 1253, the letter of invitation reduced anxiety about breast problems in
      39.7%, increased anxiety in 24.6%, and had no appreciable effect in 35.7%. In the
      1280 who attended for breast screening, the examination procedure reduced anxiety
      about breast problems in 55.9%, increased anxiety in 12.8%, and had no
      appreciable effect in 31.3%. In a smaller sample (n = 33) who completed
      questionnaires at recall, there were significant increases in PCQ-measured
      anxiety. Throughout the study, the PCQ was sensitive to change in anxiety over
      breast problems. We conclude that screening procedures can either increase or
      reduce anxiety about breast problems, or have no appreciable effect. Subjects'
      perception of the impact of receiving the letter of invitation and undergoing the
      screening examination procedure is related to previous levels of concern over
      breast problems. Conclusions about the psychological effect of breast screening
      cannot be drawn without consideration of the time and place of the baseline
      assessment. Participants in breast screening programmes therefore cannot be
      considered a homogeneous entity. Caution should be exercised when assessing the
      impact of screening procedures on entire populations as this approach might mask
      an important diversity of response.

PMID- 8733331
TI  - An audit of the use of sphygmomanometers.
AB  - This survey assessed the measurement of blood pressure and use of
      sphygmomanometers by general practitioners in Humberside and Yorkshire in 1988.
      All registered practitioners were sent a questionnaire--1223 (58%) returned it
      completed. Their responses showed that 269 (22%) had an aneroid sphygmomanometer
      only, and that 120 (10%) had a random zero sphygmomanometer; 700 (57%) had
      special cuffs for obese patients, and 558 (46%) had special cuffs for children;
      228 (23.5%) had never had their sphygmomanometers serviced ('never' corresponding
      to a mean time of 5.75 years), while 23% had patients who measured their own
      blood pressure. These findings suggest that the British Hypertension Society's
      recommendations on servicing and cuff use are not always applied. A formal audit
      of the use of different types of sphygmomanometer in general practice may
      encourage and improve accuracy and uniformity in blood pressure recording.

PMID- 8733332
TI  - Markedly elevated erythrocyte sedimentation rates: consideration of clinical
      implications in a hospital population.
AB  - In order to evaluate the clinical significance of very high erythrocyte
      sedimentation rates (ESRs) we studied 100 consecutive men in a VA Medical Center
      whose Westergren ESR was more than 100mm/hr. All were followed for up to six
      months and the ESR-requesting physicians were interviewed. A total of 162
      diagnoses known to be associated with an elevated ESR were present in the 90
      patients available for follow up. As in most previous series on very high ESRs,
      infections (seen in 43 patients) were the most common diagnoses. Other diagnoses
      included: malignancy (16), rheumatologic disease (30), other inflammatory
      diseases (seven), renal disease (25), and miscellaneous problems (38). Evaluation
      of 16 patients led to a diagnosis that had not initially been apparent--the ESR
      requesting physician did not consider that a high ESR was instrumental in guiding
      him towards any of these delayed diagnoses. Most of the markedly elevated ESRs in
      this patient population, requested in the context of already evident serious
      multisystem disease, contributed little diagnostic information.

PMID- 8733333
TI  - The lima success story--whither other arterial grafts--are vein grafts obsolete?
AB  - The long-term benefit of myocardial revascularisation depends largely upon the
      continued patency of bypass grafts, but the long-term patency of vein grafts is
      poor. To improve the results of myocardial revascularisation, either measures to
      increase the patency of saphenous vein grafts or alternative conduits are
      required. Use of the left internal mammary artery as a graft is known to increase
      survival, and this has prompted wider use of other arterial grafts in the
      expectation that they will further enhance the long-term results of coronary
      artery bypass. This policy is based upon sound theory, but convincing evidence
      that it improves survival is lacking. Meanwhile, advances in the understanding of
      the pathology of vein graft occlusion have given rise to new methods of
      increasing vein graft patency. While these techniques are, as yet, only
      experimental, if translated into clinical practice, the places of arterial and
      venous grafts may require further assessment.

PMID- 8733334
TI  - Domiciliary oxygen.
AB  - Major studies have shown that LTOT improves survival in patients with COPD,
      although the precise mechanism remains unclear. There are established guidelines
      for prescription, but these are often disregarded. This is perhaps partly because
      oxygen concentrators and cylinders are prescribed by general practitioners unable
      to carry out a full assessment of patients' suitability for oxygen therapy.
      Patients who are thought to be suitable for oxygen therapy should be referred to
      a respiratory physician with the facilities to carry out a full evaluation of
      their needs. It is important not to neglect other aspects of treatment when
      assessing a patient for domiciliary oxygen. Bronchodilator therapy should be
      maximised with or without inhaled steroids, and patients will often also benefit
      from a moderate amount of regular exercise as part of the overall pulmonary
      rehabilitation programme.

PMID- 8733335
TI  - Doxazosin: a new approach to hypertension and benign prostatic hyperplasia.
AB  - Doxazosin, a selective alpha 1-adrenoceptor antagonist, is an established first
      line antihypertensive agent that is being introduced for the management of benign
      prostatic hyperplasia. Hypertension and benign prostatic hyperplasia are linked
      by the sympathetic nervous system, which has an aetiologic role in both
      conditions. The alpha 1-adrenoceptor is a mediator of increased tension, both in
      vascular and prostatic smooth muscle. Studies have shown that doxazosin, through
      its balanced action on alpha 1-adrenoceptor subtypes, reduces blood pressure and
      improves other risk factors for coronary heart disease, such as lipid profile,
      insulin sensitivity, left ventricular hypertrophy, platelet aggregation and
      fibrinolysis. Data are now accumulating to show that doxazosin improves urinary
      flow rates and symptoms in patients with benign prostatic hyperplasia. These
      effects have been demonstrated in controlled clinical studies, within weeks, and
      long term. Since hypertension and benign prostatic hyperplasia are widespread and
      often undiagnosed in the community, particularly with increasing age, doxazosin
      may be a particularly appropriate therapy for the considerable number of older
      men with both conditions.

PMID- 8733336
TI  - Changing incidence of atrial fibrillation following coronary artery bypass
      grafting: a retrospective analysis.
AB  - The cases of 455 consecutive patients undergoing coronary artery bypass grafting
      (CABG) in one unit between 1990 and 1993 were retrospectively analysed with
      particular reference to the incidence of atrial fibrillation (AF), and with
      reference to any postoperative management that might have influenced this
      incidence. The recorded incidence of AF fell from 21% in 1990 to 11% in 1993.
      During this same period: the use of potassium chloride (KCl 20-40mmol/l)
      supplements in the intravenous fluid replacement during the immediate
      postoperative period increased from 0-96%; the use of intravenous frusemide
      decreased from 12-3%; and the practice of prescribing up to four Frumil
      (frusemide/amiloride hydrochloride) tablets daily was replaced by a more usual
      one tablet daily. Although the aetiology of AF post cardiac surgery is
      multifactorial, these three factors are implicated in the decreasing incidence of
      this complication in one unit.

PMID- 8733337
TI  - Sterile pyuria: consider chlamydial infection.
AB  - We report the cases of two men referred to a genitourinary medicine clinic with
      sterile pyuria and subsequently found to have their urethras infected with
      Chlamydia trachomatis. Chlamydial infection should be considered in the
      differential diagnosis of sterile pyuria, particularly in young, sexually active
      males. We discuss the consequences of inadequate treatment of the index case.

PMID- 8733338
TI  - Appendiceal mass: interval appendicectomy should not be the rule.
AB  - Appendicitis is the most common acute abdominal condition in Libya. Delay can
      result in the presentation of a patient with generalised peritonitis or an
      appendiceal mass. Clinical diagnosis of an appendix mass was made in 30 patients
      over three years at the Central Hospital: three required emergency appendicectomy
      within 48 hours of diagnosis, and another two had an elective appendicectomy for
      recurrent right iliac fossa pain two and three months after presentation,
      respectively. The remaining 83%, who were followed up for six months to three
      years (mean 15.5 months), did not require surgical intervention. An appendiceal
      mass should no longer be regarded as an indication for interval appendicectomy.

PMID- 8733339
TI  - Congenital vallecular cyst: a cause of failure to thrive.
AB  - Congenital vallecular cysts are fairly uncommon, but can lead to death. They may
      present as failure to thrive. This case emphasises the value of plain radiographs
      of the neck. Direct laryngoscopy is mandatory to confirm diagnosis and ablate the
      lesion satisfactorily. Laryngomalacia should be a diagnosis of exclusion.
      Adequate marsupialisation is necessary to prevent recurrence.

PMID- 8733340
TI  - Two-level intervertebral disc herniation in an adolescent.
AB  - A two-level intervertebral disc prolapse is a rare circumstance in adolescents.
      We describe the case of a 19-year-old man who suffered a deceleration traum and
      developed simultaneous large intervertebral disc herniations at L4/5 and L5/S1.
      The aetiology is discussed and, in accordance with the current literature, it is
      pointed out that clinical findings due to intervertebral disc herniations in
      young people do not necessarily correspond with the extent of the disease.

PMID- 8733341
TI  - Hepatocellular carcinoma presenting as a septicaemia-like illness in an African
      adolescent.
AB  - Although primary hepatocellular carcinoma (PHC) is quite common in adults in
      Africa, it is very rare in those under 25. The clinical diagnosis is usually
      straightforward by the time patients present and it is unusual to encounter
      differential diagnostic problems. We report an unusual clinical manifestation of
      PHC at the very young age of 15 years. The case presented clinically as a
      septicaemia-like illness that was initially thought to be typhoid. The patient
      died within 72h of presentation and the true diagnosis was only made at post
      mortem. This case simultaneously highlights several problems commonly encountered
      in medicine in the developing world: late presentation, self-medication, and
      investigative and diagnostic difficulties related to inadequate facilities.

PMID- 8733342
TI  - Life-threatening tardive dyskinesia.
AB  - We present the case of a patient with severe tardive dyskinesia that led to
      dehydration. Clinicians need to recognise that tardive dyskinesia is a
      potentially life-threatening condition, and familiarise themselves with its
      management.

PMID- 8733343
TI  - Munchausen's syndrome and HIV infection: a trap for the unwary.

PMID- 8733344
TI  - Open reduction and internal fixation of condylar fractures via an extended
      bicoronal approach with a masseteric myotomy.
AB  - Although condylar fractures of the mandible may be treated by closed reduction
      and appropriate physiotherapy, open reduction and internal fixation is indicated
      in specific circumstances. We report 25 cases of a previously unreported method
      of exposure of condylar fractures using an extended bicoronal approach combined
      with myotomy of the masseter muscle. Acceptable reduction and fixation was
      achieved in all cases with an early return to function. The incidence of
      complications was low, with three mild temporary facial palsies which had
      resolved by the sixth postoperative week and one haematoma beneath the bicoronal
      scalp flap. A cosmetically acceptable scar was produced in all cases. The
      excellent surgical exposure and protection of the facial nerve, combined with
      cosmetically acceptable scars, commend the use of this technique.

PMID- 8733345
TI  - The submental island flap.
AB  - The submental island flap is a reliable source of skin of excellent colour,
      contour and texture match for facial resurfacing and leaves a well hidden donor
      site. The flap is safe, rapid and simple to raise. We report on its use in 12
      cases of facial or intraoral reconstruction. Complications were few. However,
      there was one case of complete flap loss following its use in a reverse flow
      manner, due to the presence of an unreported, but constant, valve in the venous
      system of the face. We believe this flap to be a worthwhile addition to the
      existing surgical armamentarium.

PMID- 8733346
TI  - Arterialised venous groin flap: case report.
AB  - A defect of the right cheek, mastoid and inferior auricular region in a 16-year
      old female after resection of a squamous cell carcinoma was covered with a free
      arterialised venous groin flap. As the conventional groin flap did not include
      the superficial circumflex iliac artery, one of the two superficial circumflex
      iliac veins was arterialised and the other was used as the draining vein. Part of
      the flap underwent full-thickness necrosis; however, the area that survived was
      enough to cover the defect.

PMID- 8733347
TI  - The sternocleidomastoid myocutaneous flap: a reappraisal.
AB  - The sternocleidomastoid myocutaneous flap was described 40 years ago. However,
      its reliability has been a matter of discussion, mainly because of its random
      blood supply and subsequent tendency to necrosis. This paper describes the use of
      the sternocleidomastoid island myocutaneous flap, superiorly based, in 10
      patients with good results. In these patients, the superior thyroid artery was
      sacrificed and the skin paddle was incised directly over the muscle, as described
      by Ariyan. We believe this approach assures the usefulness of the flap and
      justifies its expanded utilization.

PMID- 8733348
TI  - The second dorsal metacarpal artery flap with double pivot points.
AB  - A flap with double pivot points based on the second dorsal metacarpal artery was
      used in 13 cases with no complete failures. In 2 cases, the branches of the
      radial nerve were included in the flap. In 1 case, the flap was used as a
      tenocutaneous flap with a segment of the extensor indicis proprius tendon. To
      obtain a flap with double pivot points, the dissection of the vascular pedicle of
      a distally based second dorsal metacarpal flap is continued proximally under the
      second dorsal metacarpal artery up to its origin. In this flap the main pivot
      point coincides with the origin of the SDMA and the second pivot point with the
      entry point of the recurrent cutaneous branch into the flap. We found this flap
      to be very versatile, reliable, and quite easy and quick to raise. We report our
      experience with this flap as a very useful addition to reconstructive procedures,
      especially for thumb defects.

PMID- 8733349
TI  - The second web bilobed island flap for thumb reconstruction.
AB  - The second web bilobed island flap is described. The flap includes skin from the
      second web of the hand and the dorsum of the index and middle fingers. Usually
      the flap is based on the first and second dorsal metacarpal arteries, but it can
      be used with just the first dorsal metacarpal vessels in its pedicle. Sensation
      of the flap is provided by branches of the radial nerve. The flap has been
      successfully used to reconstruct 11 injured thumbs.

PMID- 8733350
TI  - The origins of the concept of muscle flaps.
AB  - Contrary to contemporary opinion, the principles of muscle flap preparation and
      the use of muscle flaps for, among other conditions, chronic osteomyelitis were
      described in Europe in the 19th century. This article introduces significant
      works from the turn of the century which would have greatly contributed to
      today's knowledge had they not fallen into obscurity.

PMID- 8733351
TI  - The distally based posterior tibial myofasciocutaneous island flap in foot
      reconstruction.
AB  - We report 3 cases of foot reconstruction with a distally based posterior tibial
      island flap incorporating both muscle and a fasciocutaneous part. The medial half
      of the soleus muscle which is included in the flap is well vascularised and can
      be used to fill cavities, for example after debridement of chronically infected
      wounds.

PMID- 8733352
TI  - The injured foot: cutaneous coverage with a distally based posterior tibial cross
      leg flap.
AB  - Treatment of extensive soft tissue defects of the foot has long been a
      challenging problem for the reconstructive surgeon. We report a series of 5
      injured feet with major soft tissue loss and significant bony injury, treated
      with distally based cross leg flaps based on the posterior tibial artery, with
      satisfactory cosmetic and functional results. The survival of the flap was
      complete in 4 of the 5 patients; in one case, the flap suffered about 2-3 cm
      distal partial necrosis. The mean hospital stay was 30 days, and walking without
      ambulatory support was possible about 60 days postoperatively. We consider this
      procedure a potential alternative to microvascular techniques for the treatment
      of severe foot injuries, in an area where microsurgery reconstruction is fraught
      with difficulties.

PMID- 8733353
TI  - Early division of pedicled flaps using a simple device: a new technique.
AB  - A simple occlusion clamp with screws used to achieve early division of two
      staged, distant pedicled flaps is presented. The device is applied to the bridge
      of a distant flap on the 5th postoperative day and is gradually tightened. It was
      used on 20 consecutive pedicled flaps in 20 patients: 5 abdominal flaps, 4
      superficial external pudendal artery (SEPA) flaps, 9 cross leg flaps, 1 groin
      flap and 1 medial arm flap. In 17 patients, the flaps were divided successfully
      between the 9th to the 14th day (Mean: 10 days). The device was removed in 3
      patients when ischaemic changes became apparent; their flaps however survived
      completely and were divided after a longer interval. The principles on which the
      device works, the technique, feasibility, and advantages of using the device for
      early flap division are discussed.

PMID- 8733354
TI  - Evaluation of lymphatic drainage in free flaps by lymphoscintigraphy: a
      preliminary study.
AB  - Lymphatic drainage from free flaps was studied by lymphoscintigraphy in 14
      patients in whom free vascularised flaps were used to cover defects caused by
      trauma or tumour ablation. Lymphoscintigrams were done after intradermal
      injection of Technetium-99m-Dextran in the flap and in the corresponding
      contralateral normal area. The retention of radioactivity at the injection sites
      after 1 h was computed and expressed as percentages of baseline activity at the
      time of injection. 25 studies were done in 14 patients at intervals varying from
      9 days to 6 years postoperatively. In all cases, radioactivity was detected
      beyond the flaps in the lymphatic channels and draining lymph nodes. There was no
      significant difference (P = 0.27) between the retention of activity in the flaps
      (mean 88.68%; s.e.m. 1.25) and that in the corresponding contralateral control
      area (mean 86.88%; s.e.m. 1.35). This study shows that lymphatic drainage in a
      free flap is established early after surgery.

PMID- 8733355
TI  - Four alginate dressings in the treatment of partial thickness wounds: a
      comparative experimental study.
AB  - Alginate-based absorption materials for wound treatment are meeting with
      increasing clinical acceptance. The purpose of this study was to compare four
      different calcium alginate dressings (Algosteril, Comfeel Alginate, Kaltostat and
      Sorbsan) with respect to wound fluid retaining ability, adherence, dressing
      residues, epithelialisation and inflammatory cell infiltration using a
      standardised partial-thickness wound model in domestic pigs. Wound fluid spread
      laterally onto surrounding normal skin by about 40% more with Sorbsan than with
      the other alginate dressings after 24 h of treatment (P = 0.026). The
      corresponding figure after 66 h of treatment was 20% (P = 0.030). Algosteril
      (mean 1.7 [sem 0.3]) adhered significantly (P = 0.014) more to the wounds than
      Comfeel Alginate (mean 0.2 [0.2]). Kaltostat (mean 1.8 [0.3]) left significantly
      (P = 0.038) more dressing residues on the wound surface at dressing removal than
      the Comfeel Alginate dressing (mean 0.8 [0.2]). In the effect on
      epithelialisation or dermal inflammation there was no statistically significant
      difference at significance level 5% among the four alginate dressings, as
      assessed by light microscopy. In summary, the four alginate dressings showed
      significant differences in important handling characteristics and did not differ
      significantly in their effect on epithelialisation.

PMID- 8733356
TI  - Takayasu's disease and the acromiothoracic axis.

PMID- 8733357
TI  - Levator lengthening for the retracted upper eyelid.

PMID- 8733358
TI  - Subclassification of polydactyly.

PMID- 8733359
TI  - Malignant melanoma in childhood.
AB  - Malignant melanoma (MM) is rare in childhood. We report 24 cases of MM in
      children 16 years old or less, whose histopathological specimens were referred to
      our department from 1981 to 1993. In only three cases was the diagnosis of MM
      made clinically. In some cases histological distinction from benign Spitz naevi
      was difficult, but other cases were referred because of a reluctance to diagnose
      MM in a child. One child died of disseminated disease, two developed nodal
      metastases and two developed local recurrence. Of all the lesions, the one which
      was considered to show the least difference from a benign naevus histologically
      occurred in the child who died. Awareness that MM, although rare, does occur in
      childhood, is vital. However, diagnosis is difficult, both clinically and
      histopathologically.

PMID- 8733360
TI  - A prospective study of congenital melanocytic naevi: progress report and
      evaluation after 6 years.
AB  - A prospective study of children with large congenital melanocytic naevi (CMNs) is
      in progress. Its aims are to observe the natural history and inheritance of CMNs,
      to record associated pathologies, and eventually to evaluate the effects of
      treatment. Information is obtained by patient-completed questionnaires and
      clinical assessment. One hundred and thirty-three children have been followed for
      a total of 452 patient years. The female/male ratio is 3:2. The characteristics,
      size and distribution at birth of the CMNs in this group of patients, and their
      development and associated abnormalities, are documented. After 5 years, affected
      children were compared with a matched cohort of normal children. Although the
      prevalence of neurological and developmental defects was higher in affected
      children, no malignant melanomas have been reported to date. The families of
      affected children had higher numbers of naevi and cafe-au-lait spots than those
      of normal children, suggesting a possible hereditary component. The mothers of
      affected children also reported an increased incidence of influenza-like illness
      and of severe nausea and vomiting in pregnancy. This study will continue for a
      further 4 years, in the first instance, after which we will seek relationships
      between characteristics of the naevi and outcome.

PMID- 8733361
TI  - Health education about sun and skin cancer: language, ideas and perceptions of
      young children.
AB  - Excessive sunlight in early childhood is thought to be a risk factor for skin
      cancer. We report the use of the 'draw and write' technique for determining
      changing perceptions, attitudes and knowledge of young children (aged 4-12 years)
      to the sun and skin cancer. Children were asked to draw pictures and label them
      in response to a series of carefully worded invitations and questions. The
      captions were then analysed to assess changing views and perceptions about
      particular issues in relation to behaviour in the sun. Four hundred and sixty
      children completed the exercise. An increasing spiral of knowledge with age about
      effects of the sun and appropriate behaviour was demonstrated. The study revealed
      a relatively high level of knowledge. Misconceptions and stereotypes were
      demonstrated. This technique is a simple and effective way of eliciting
      information from children about health issues. It provides baseline data for
      producing material for health education for children in relation to sun and skin.
      It is also a method of assessing the effectiveness in young children of health
      promotion initiatives.

PMID- 8733363
TI  - Cutaneous neoplasia following PUVA therapy for psoriasis.
AB  - To determine the risk of cutaneous neoplasia following photochemotherapy (PUVA),
      we reviewed patients with psoriasis treated at our unit between 1979 and 1991.
      Two hundred and forty-five patients were assessed, with a median duration of
      follow-up of 9.5 years. Fifty-nine per cent were male, and 41% female. The median
      number of exposures was 59, and the median total dose was 133 J/cm2 for the group
      as a whole. Non-melanoma skin cancers (NMSC) occurred in six individuals (2.4%).
      Basal cell carcinoma occurred in all six and one individual also developed four
      squamous cell carcinomas and Bowen's disease of the penis. No cases of malignant
      melanoma were recorded. Patients who developed NMSC received a median number of
      225 exposures and a median cumulative dose of 654 J/cm2. Compared with a control
      study population in West Glamorgan, Wales, there was a 1.4 (95% confidence limits
      (CL) 0.5 and 3.1) times increased risk of NMSC. A statistically significant
      increased incidence of NMSC was found for patients who had received 100 or more
      exposures, and 250 or more J/cm2, with risks of 3.7 (95% CL 1.0 and 9.5), and 4.0
      (95% CL 1.1 and 10), respectively. A PUVA dose of < 250 J/cm2 or < 100 exposures
      conferred a minimal increase in risk of NMSC in our study population.

PMID- 8733362
TI  - Integrity of the permeability barrier regulates epidermal Langerhans cell
      density.
AB  - Previous studies have shown that barrier requirements regulate epidermal liquid
      and DNA synthesis. In the present study, we examined the possibility that the
      integrity of the permeability barrier influences epidermal Langerhans cells
      involved with the immune response. Barrier disruption was achieved by treatment
      of human skin with acetone, sodium dodecylsulphate (SDS), or tape stripping,
      until a 10-20-fold increase in transepidermal water loss was achieved. Serial
      biopsies were performed 6-168 h after treatment, and Langerhans cells were
      complexed with anti-CD1a (Leu6) or S-100 antibodies, and visualized with an
      immunoperoxidase technique. Acetone treatment resulted in an increase in
      epidermal Langerhans cell density, reaching a maximum of 94% over control (P <
      0.01) by 24 and 48 h post-treatment. Following SDS treatment or tape stripping,
      epidermal Langerhans cell density was increased by 100 and 175% (P < 0.01),
      respectively. There was a linear correlation between the degree of barrier
      disruption and the increase in epidermal Langerhans cell density. Studies with
      the Ki-S3 proliferation-associated nuclear antigen revealed a two- to threefold
      increase in epidermal proliferation after barrier disruption. The time curves of
      the increase in Langerhans cell density and the increase in epidermal
      proliferation were similar, suggesting that there was a coordinate regulation. In
      contrast with our previous studies employing patch test reactions to allergens or
      irritants, disruption of barrier function neither resulted in an increased dermal
      Langerhans cell density, nor influenced T lymphocytes (CD3+, Leu4+), macrophages
      (KiM8+), ICAM-1 or ELAM-1 expression in the skin. In addition, barrier disruption
      did not result in either dermal inflammation or epidermal spongiosis. In summary,
      these findings support our hypothesis that the permeability barrier influences
      epidermal Langerhans cell density, which is involved in maintaining an
      immunological barrier.

PMID- 8733364
TI  - Increased expression of inducible nitric oxide synthase in psoriatic skin and
      cytokine-stimulated cultured keratinocytes.
AB  - Since nitric oxide (NO) has been implicated in the pathogenesis of various
      hyperproliferative and inflammatory diseases, the mRNA expression of constitutive
      nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) were
      investigated in psoriatic skin by reverse transcriptase coupled to the polymerase
      chain reaction (PCR). The study showed that the mRNA expression of brain nitric
      oxide synthase (bNOS), one of two isoforms of cNOS, was weak in both psoriatic
      plaques lesions and uninvolved skin, while mRNA transcripts for the second
      isoform, endothelial nitric oxide synthase (eNOS), were not detectable using the
      present method. In contrast, the mRNA expression of iNOS was markedly increased
      in lesional skin as compared to uninvolved skin. Cultured human keratinocytes
      exposed to a combination of interleukin-1 beta (IL-1 beta) and tumour necrosis
      factor-alpha (TNF-alpha) for 4 h, showed strong gene expression of iNOS, while in
      24 h, the expression had returned to baseline expression. In summary, the study
      demonstrates that mRNA for the inducible form of NOS is over-expressed in
      psoriatic lesions. The cause of this may be the local presence of inflammatory
      cytokines. These findings imply that iNOS may play an important part in local
      regulation of NO synthesis in psoriasis and other inflammatory dermatoses.

PMID- 8733365
TI  - Locations of synthesis of hair structural proteins in human anagen follicles.
AB  - Live tissue containing cells of the presumptive hair shaft (PHS), was obtained by
      microdissection of human anagen hair follicles. Whole PHS, as well as PHS further
      dissected into three levels of hair development, were subsequently used in
      protein solubilization procedures. Single- and two-dimensional polyacrylamide gel
      electrophoresis (PAGE) of radiolabelled extracts, with fluorography, enabled
      comparison of hair and PHS keratin proteins. Fluorographs demonstrated the major
      classes of protein comprising the intermediate filaments (IF) and matrix of hair
      keratins. In addition, extracts from various levels of PHS tissue have provided
      direct evidence for the locations of synthesis of these protein moieties. Thus,
      IF and matrix proteins are synthesized sequentially in PHS. A previously
      unobserved polypeptide component, not present in hair extracts, has been
      identified and found to vary in relative proportions when compared with the major
      IF and matrix protein classes as PHS cells differentiate to form hair. In the
      absence of reliable methods for extraction of human hair, PHS provides an
      alternative source of material, despite the extra burden of follicle collection
      and specimen preparation. The procedures described provide a new basis for
      studying human hair defects and are potentially useful for comparing human hair
      proteins in a variety of situations.

PMID- 8733366
TI  - Soluble intercellular adhesion molecule-1 and soluble E-selectin levels in
      patients with atopic dermatitis.
AB  - The serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and
      soluble E-selectin (sE-selectin) were determined by double determinant
      immunoassay (DDIA), in 37 patients with atopic dermatitis (AD) and 31 age- and
      sex-matched healthy control subjects. Both sICAM-1 and sE-selectin levels were
      significantly higher in patients with AD than in healthy controls (P < 0.01), and
      were correlated with disease severity. A longitudinal study of patients with AD
      revealed that the levels of sICAM-1 decreased in those in whom symptoms improved.
      The sICAM-1 levels were significantly correlated with those of sE-selectin. Our
      studies suggest that such high levels of serum sICAM-1 and sE-selectin may affect
      the immune response in patients with AD. The levels of sICAM-1 and sE-selectin
      may be a useful immunological parameter for monitoring disease activity in AD.

PMID- 8733367
TI  - Identification of contact allergens in unmodified rosin using a combination of
      patch testing and analytical chemistry techniques.
AB  - In order to investigate the contact allergens in the unmodified colophony (rosin)
      used in routine patch testing, preparative chromatographic techniques were used
      to separate its components which were then patch tested on colophony-sensitive
      individuals. The chemical structure of the dermatologically active components was
      elucidated using mass spectrometry, nuclear magnetic resonance and infra-red
      techniques. The study shows that oxidized resin acids are stronger sensitizers
      than the resin acids themselves, the most potent contact allergen being 7
      oxydehydroabietic acid (purity 92%). At naturally occurring concentrations
      (relative to abietic acid) all unoxidized resin acids were found to play an
      insignificant part, individually, in colophony dermatitis, except abietic acid
      (purity 99%), which was found to be a weak but important allergen. The commercial
      Trolab abietic acid preparation (unknown purity) was found to be dermatologically
      more active than purified abietic acid.

PMID- 8733368
TI  - The relationship between IgE-mediated and cell-mediated hypersensitivities in an
      unselected Danish population: the Glostrup Allergy Study, Denmark.
AB  - In this study, we have assessed the relationship between IgE-mediated and cell
      mediated hypersensitivities in an unselected population living in western
      Copenhagen, Denmark. A total of 793 subjects, aged 15-69 years, were studied.
      Measurements of total serum IgE, prick tests with aero-allergens and patch tests
      with environmental haptens were performed in 561 (70.7% of 793) subjects. One or
      more positive prick tests were present in 28.4%, and contact sensitization
      occurred in 15.2%. When adjusted for the effects of sex and age, the probability
      of contact sensitization to one or more hapten was independent of serum IgE level
      (the odds ratio value (OR) = 1.0; 95% confidence interval (CI) = 0.7-1.4), and
      the probability of contact sensitization was independent of the number of
      positive prick tests (OR = 1.0; CI = 0.8-1.2). Contact sensitization appeared to
      be independent of enhanced IgE responsiveness in an unselected adult population.

PMID- 8733369
TI  - Contact allergy to gold in dental patients.
AB  - Gold sodium thiosulphate (GSTS) in patch test series commonly yields positive
      reactions. In this study of dental patients, the clinical relevance of these
      positive reactions, the suitability of gold compounds as patch test materials,
      and value of the lymphocyte proliferation test in gold contact allergy, were
      evaluated. The frequency of positive patch test reactions to GSTS was 12.4% in
      the dental series. Fifty-two patients, only two of whom were male, were studied.
      Thirteen (25%) had had symptoms from jewellery or dental restorations. However,
      in most cases gold allergy was subclinical. A 10% aqueous solution of gold sodium
      thiomalate (GSTM) was almost as good as 0.5% GSTS in petrolatum as a marker of
      gold contact allergy, but 0.001% potassium dicyanoaurate (PDCA) yielded a high
      percentage of false-negative results. Seventy-three per cent of the subjects with
      positive patch tests to GSTS responded to gold compounds in vitro in the
      lymphocyte proliferation test, whereas 13 controls without gold contact
      sensitivity were negative. Consistent results in skin and lymphocyte
      proliferation tests provide support for the concept that gold salt-induced
      'allergic-like' reactions are truly allergic in nature.

PMID- 8733370
TI  - A study of 72 patients with contact allergy to tioconazole.
AB  - Over a 3 1/2 year period, from 1991 to 1994, we detected contact allergy to
      tioconazole in 72 patients by epicutaneous testing. During this period,
      tioconazole was included in the standard series of epicutaneous tests. Except for
      the first 6 months, the incidence of positive patch test reactions to tioconazole
      was over 1% of patients tested for contact allergy. As well as those tested with
      the standard series, 18 additional patients with tioconazole allergy were
      detected by direct testing with an imidazole patch test series. Of the various
      imidazole derivatives, tioconazole was the most important contact allergen. About
      half of patients with contact hypersensitivity to tioconazole, had additional
      contact allergies detected by the standard series. Men and women were equally
      affected. The present study suggests that tioconazole is an important contact
      allergen, which should be included into the patch test series in countries where
      it is used as a topical antifungal agent.

PMID- 8733371
TI  - Paraphenylene diamine, a contact allergen, induces oxidative stress in normal
      human keratinocytes in culture.
AB  - During the course of evaluating the interaction between allergens and
      keratinocytes in the pre-immunological phase of contact sensitization, we have
      studied the effects of paraphenylene diamine (pPD) on membrane lipid peroxidation
      and on intracellular antioxidant levels in cultured human keratinocytes. pPD is
      an aromatic amine which undergoes spontaneous oxidation in culture medium,
      generating short-lived free radical species including oxyradicals. Following
      exposure to non-toxic concentrations of pPD (0.5-10 micrograms/ml), we have
      evaluated the fatty acid pattern of membrane phospholipids as a target of
      peroxidative damage, and the intracellular level of reduced glutathione (GSH),
      the activity of superoxide dismutase (SOD), and that of catalase (CAT) as
      parameters of the antioxidant system. Depending on pPD concentration and the
      period of exposure, peroxidative damage with a significant decrease in membrane
      polyunsaturated fatty acids, was detected. Concentrations between 0.5 and 2
      micrograms/ml produced an initial increase and then a decrease in both SOD and
      CAT activities, and in the oxidation of GSH, up to 12 h. After 24 h, when all the
      pPD had decomposed, recovery of the initial levels of the antioxidants was
      detected. Concentrations over 5 micrograms/ml induced a progressive decrease in
      both the enzymatic activities and the GSH concentrations. These results are
      consistent with the view that oxidative stress can be an essential event in the
      pre-immunological phase of contact sensitization.

PMID- 8733372
TI  - Differentiation-associated localization of small proline-rich protein in normal
      and diseased human skin.
AB  - The expression of SPRR (small proline-rich protein) was investigated in normal
      human skin and in diseased skin from patients with psoriasis, squamous cell
      carcinoma, basal cell epithelioma, naevus pigmentosus, ichthyosis vulgaris and
      several inflammatory skin diseases, by immunohistochemical staining. A polyclonal
      antibody was raised against a synthetic peptide for a C-terminal common region
      for SPRR1 and SPRR3. In immunoblot analysis, a positive band of 18 kDa was
      detected, which showed the presence of SPRR1 in human epidermal keratinocytes. In
      normal epidermis, positive staining for SPRR was observed in keratinocytes in the
      granular layer and the uppermost or two spinous cell layers, with no staining of
      the other spinous or basal layers. The staining was obvious at the cell
      periphery, weak at the cytoplasm, and absent in the nucleus. Staining was
      observed in several outer layers of the follicular infundibulum to the isthmus.
      No staining was detected in the inner root sheath of the hair follicles, hair
      matrix, sebaceous gland, eccrine gland, eccrine duct, melanocytes, Langerhans
      cells or fibroblasts. The arrectores pilorum, striated muscles, muscle layers of
      vessels, and myoepithelia of eccrine gland, were weakly stained. In psoriatic
      skin, stained keratinocytes were distributed in the spinous cell layers except
      for the basal layer. In ichthyosis vulgaris, SPRR was barely expressed in the
      uppermost living cell layers of the epidermis. In epidermolytic hyperkeratosis,
      degenerated squamous cells widely expressed SPRR. In Darier's disease,
      dyskeratotic cells were clearly stained. In squamous cell carcinoma, staining was
      observed in keratotic cells around horny pearls. In basal cell epithelioma,
      naevus pigmentosus, and malignant melanoma, the tumour cells or naevus cells were
      not stained. The distribution of SPRR was similar to that of involucrin in normal
      and several diseased skin, except for ichthyosis vulgaris. We conclude that SPRR
      is expressed in close association with epidermal differentiation in normal skin
      and skin diseases. The alteration of the expression of the proteins correlated to
      terminal differentiation, and differs from disease to disease.

PMID- 8733373
TI  - Safety of long-term high-dose minocycline in the treatment of acne.
AB  - Minocycline is widely used as a second-line antimicrobial for acne vulgaris. Some
      patients require doses of up to 200 mg daily to control their acne. To assess the
      long-term safety of minocycline when used at higher doses, 700 patients treated
      with minocycline at doses of 100 mg daily, 100/200 mg on alternate days and 200
      mg daily, were recruited. The mean duration of treatment was 10.5 months. Side
      effects were monitored and full blood count, blood urea, electrolytes and liver
      function tests were carried out on 200 of the 700 patients. Side-effects were
      recorded in 13.6%, and included vestibular disturbance, candida infection,
      gastrointestinal disturbance, cutaneous symptoms (pigmentation, pruritus,
      photosensitive rash and urticaria) and benign intracranial hypertension.
      Pigmentation was the only side-effect found to be significantly increased in
      patients taking higher doses of minocycline, as compared with lower doses (P <
      0.01). All patients with pigmentation had taken a total cumulative dose of over
      70 g. No significant abnormalities were found in any of the haematological and
      biochemical profiles. We conclude that minocycline, at doses of up to 200 mg/day,
      is safe, long-term, for acne, when such doses are clinically necessary.

PMID- 8733374
TI  - A survey of the prevalence of biting by the Blandford fly during 1993.
AB  - To assess the frequency of bites by the Blandford fly, a postal survey was
      carried out at the end of the 1993 biting season. Questionnaires were sent to a
      random sample of 1,500 people, selected from the lists of the two general
      practices in Blandford Forum, and satisfactory replies were obtained from 1203
      (80%). Altogether, 194 (16%) of subjects reported one or more insect bites,
      during the 2-month season, that had led to skin swelling more than 2.5 cm across.
      Of these, more than a quarter had suffered associated systemic symptoms, in the
      form of fever or joint pain. One hundred and forty-nine had used medications for
      bites, 20 had consulted a doctor, and seven had taken time off work or school.
      Bites were more common in females (22%) than males (9%). This difference was due
      largely to a higher frequency of bites on the legs. Risk might be reduced
      substantially in women by wearing trousers, especially in those who spend a lot
      of time outdoors.

PMID- 8733375
TI  - Treatment of proliferative haemangiomas with the 585 nm pulsed dye laser.
AB  - Haemangiomas usually develop within the first few weeks of life, most regressing
      spontaneously before the age of 7 years. Some may ulcerate or compromise a vital
      function, in which case systemic corticosteroids, surgery or radiotherapy may be
      helpful. All of these treatment modalities are associated with significant
      morbidity. Treatment with the 585 nm flashlamp pulsed dye laser is safe and
      effective in the management of superficial vascular malformations. We report
      seven patients, under 12 months of age, who presented with proliferative
      haemangiomas, causing functional impairment. Ulcerated lesions were present in
      four patients. The patients were treated with the 585 nm pulsed dye laser
      (fluences 7.0-9.25 J/cm2), at intervals of 4-8 weeks. All of the lesions showed a
      significant reduction in size, together with improvement in the colour and
      integrity of the overlying skin. Treatment with the 585 nm pulsed dye laser
      should be considered in the management of infants with early proliferative
      haemangiomas, in whom intervention is indicated.

PMID- 8733376
TI  - An immunohistochemical study of the dermal infiltrate and epidermal staining for
      interleukin 1 in 12 cases of Sweet's syndrome.
AB  - Interleukin 1 (IL-1) has been proposed as a possible mediator in Sweet's
      syndrome. We examined all cases of Sweet's syndrome (n = 12) presenting to the
      department over a 10-year period, from 1982 to 1992, for the presence of IL-1 and
      also assessed the nature of the dermal inflammatory infiltrate in those cases.
      Staining for IL-1 alpha and IL-1 beta was stronger in control tissues than in
      Sweet's syndrome. This may possibly be explained by the release of IL-1 alpha and
      IL-1 beta into the dermis in Sweet's syndrome. Contrary to recent reports, we
      found that neutrophils predominated in all cases examined, although histiocytes
      were present in increased numbers indicating their possible role in the
      pathophysiology of Sweet's syndrome.

PMID- 8733377
TI  - Apoptosis as a mechanism of keratinocyte death in toxic epidermal necrolysis.
AB  - Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are life
      threatening diseases characterized by extensive epidermal destruction. The aim of
      our study was to investigate apoptosis in keratinocytes of patients with TEN and
      TEN/SJS overlap syndrome. Keratinocytes from TEN patients were found to undergo
      extensive apoptosis. These results suggest that cell destruction in TEN occurs as
      a result of apoptosis. Our findings suggest that apoptosis inhibitory agents may
      play an important part in the therapeutic strategy of TEN.

PMID- 8733378
TI  - Lichen planus and hepatitis C virus: prevalence and clinical presentation of
      patients with lichen planus and hepatitis C virus infection.
AB  - Although cases of lichen planus (LP) associated with hepatitis C virus (HCV)
      infection have been described, the association between the two diseases has not
      been established because the geographic origin of patients could be an important
      factor in HCV prevalence in patients with LP. The serum samples of 78 consecutive
      patients with cutaneous and/or mucous LP and 82 control patients were analysed
      for the presence of antibodies to HCV by enzyme-immunoassay and for the presence
      of antigens of HCV by two-stage polymerase chain reaction (PCR). The clinical
      features of patients with LP associated with HCV infection were compared with
      patients with LP without HCV infection. Sixteen of the 78 (20%) patients had anti
      HCV antibodies. In 13 of these 16 cases (81%), HCV-RNA was detected by PCR in
      serum samples. In the 82 control patients, anti-HCV antibodies was observed in
      two (2.4%) patients. We have found a statistically significant association (P <
      0.05) between erosive LP and HCV infection. We conclude that the high prevalence
      of HCV-RNA in patients with LP provides some evidence for the role of HCV in the
      pathogenesis of LP. Our results suggest an association between erosive LP and HCV
      infection.

PMID- 8733379
TI  - Punctate palmoplantar keratoderma and malignancy in a four-generation family.
AB  - We report a large kindred in which a punctate palmoplantar keratoderma (PPK) is
      associated with malignancy, including Hodgkin's disease, renal, breast,
      pancreatic and colonic adenocarcinomas. The family was traced through four
      generations, and over 320 individuals were identified, of whom 49 had punctate
      PPK. The punctate PPK appeared to be inherited as an autosomal dominant trait
      with variable penetrance. Ten of the 43 adults (23%) with punctate PPK developed
      malignancies, and five of these developed before the age of 50. Of the 271
      unaffected individuals, six (2%) have developed malignancies, one prior to the
      age of 50. The association of keratoderma and malignancy is discussed.

PMID- 8733380
TI  - Unilateral facial angiofibromas--a segmental form of tuberous sclerosis.
AB  - Multiple facial angiofibromas are thought to be a pathognomonic and common,
      feature of tuberous sclerosis. In contrast, it is rare to see multiple
      angiofibromas limited to one side of the face. We have studied a patient with
      multiple angiofibromas of one cheek, in order to search for other manifestations
      of tuberous sclerosis and to determine the histochemical identity of the
      angiofibromas. No evidence of other pathology known to be associated with the
      tuberous sclerosis complex was uncovered. Histopathology of the unilateral
      lesions revealed focal fibroplasia and positive cellular staining for factor
      XIIIa and vimentin, similar to that described for bilateral angiofibromas. We
      suggested that the segmental expression of tuberous sclerosis, in the form of
      unilateral facial angiofibromas, may result from a postzygotic mutation.

PMID- 8733381
TI  - Hereditary angioedema caused by a point mutation of exon 7 in the C1 inhibitor
      gene.
AB  - Hereditary angioedema (HAE) is a genetic disease which may be detected
      serologically. We present a patient with HAE, in whom we examined the gene defect
      using the polymerase chain reaction. The patient presented with recurrent
      episodes of abdominal pain, or non-itchy swellings of the hands, feet, and penis.
      The serum levels of C1 inhibitor (C1-INH) and C4 were below normal. We determined
      that a single base change (C-->T) at nucleotide 1482 in the seventh exon was
      present in the C1-INH gene. This mutation converted the codon for the Gln-339 to
      a premature translation termination codon TAG. A point mutation in the C1-INH
      gene can cause type I HAE.

PMID- 8733382
TI  - First trimester DNA-based exclusion of recessive dystrophic epidermolysis bullosa
      from chorionic villus sampling.
AB  - A 28-year-old woman, who previously had had a child affected with the hereditary
      blistering skin disorder, recessive dystrophic epidermolysis bullosa, presented
      at 7 weeks' gestation for prenatal diagnosis. Genomic DNA, obtained from her, her
      husband (who is a first cousin), their unaffected child, and their previously
      affected child, was used to screen all 118 exons of the type VII collagen gene
      (COL7A1) by polymerase chain reaction (PCR) amplification followed by
      heteroduplex analysis of the PCR products. Established common polymorphisms
      within the NC-1 region of COL7A1 were informative for both the normal maternal
      and paternal alleles. In addition, a putative homozygous mutation, a G to C
      transversion at nucleotide position 7708, was identified in the affected child.
      This substitution converts a glycine residue (GGT) within the Gly-X-Y region of
      the type VII collagen triple helix into an arginine residue (CGT), and leads to
      the creation of a new MnlI restriction site. Both parents and the healthy sibling
      were shown to be clinically normal heterozygous carriers of this mutation. A
      chorionic villus biopsy was performed at 10 weeks' gestation and DNA was
      extracted from the villi. Assessment of informative intragenic markers, and the
      putative mutation, revealed that the fetus had inherited both the normal maternal
      and paternal COL7A1 alleles. Thus, first trimester DNA-based prenatal diagnosis
      predicts that this child is neither affected with recessive dystrophic
      epidermolysis bullosa, nor is an unaffected carrier of this genodermatosis.

PMID- 8733383
TI  - Tumour progression in a patient with granulomatous mycosis fungoides.
AB  - We report a patient with granulomatous mycosis fungoides whose disease
      transformed into a high grade blast lymphoma with angiocentric features within 12
      months of the initial diagnosis. This repudiates previous claims that
      granulomatous inflammation is protective in cutaneous T-cell lymphoma.

PMID- 8733384
TI  - Angiolymphoid hyperplasia with eosinophilia affecting the oral mucosa: report of
      a case and a review of the literature.
AB  - Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon disorder of
      unknown aetiology. Clinically, it is characterized by cutaneous papules or
      nodules on the head and neck, and extracutaneous involvement is rare. We report a
      30-year-old woman who had an asymptomatic submucosal nodule on the upper lip,
      which histopathologically showed features of ALHE, and review the previously
      described 15 cases of oral ALHE.

PMID- 8733385
TI  - Purely cutaneous Rosai--Dorfman disease.
AB  - Cutaneous lesions of Rosai-Dorfman disease (RDD) are usually associated with
      nodal or other extranodal localization. We describe a female patient with RDD
      clinically limited to the skin. The patient presented with asymptomatic red-brown
      papules and nodules on the legs, arms, back, and nose. Histologically, the
      lesions consisted of a proliferation of large histiocytes occasionally showing
      emperipolesis. Histiocytes were also observed within dilated lymphatic vessels.
      Immunohistochemical study showed that histiocytes expressed S-100 protein and
      both macrophage and monocyte markers. All lesions resolved completely with
      Roentgen therapy. No recurrence has been observed over a 3-year follow-up period.

PMID- 8733386
TI  - Acrodermatitis continua of Hallopeau in a patient with myelodysplastic syndrome.
AB  - Acrodermatitis continua of Hallopeau (ACH) is a rare manifestation of pustular
      psoriasis which may considerably disable affected patients. In this case report
      we confirm the efficacy of acitretin in the treatment of ACH and, in addition,
      describe the course of the myelodysplastic syndrome (MDS) from which the patient
      was suffering. During acitretin treatment, there was a transformation into acute
      myeloid leukaemia. We discuss the effect of retinoids on the bone marrow of
      normal subjects, patients with MDS, and patients with acute myeloid leukaemia.
      Our experience in the present case, and the information from the available
      literature, lead us to advise against the use of the aromatic retinoids,
      acitretin and etretinate, in patients with MDS. If such treatment is indicated,
      intensive haematological supervision is mandatory.

PMID- 8733388
TI  - Combined surgical and X-ray treatment for angiosarcoma of the scalp: report of a
      case with a favourable outcome.
AB  - Classic angiosarcoma is an uncommon malignant neoplasm of vascular
      differentiation which is highly aggressive. The diagnosis is often delayed and,
      since the response to treatment mainly depends on the size of the tumour, the
      prognosis is usually poor. Here we report a 76-year-old man in whom an extensive
      angiosarcoma of the scalp was treated by excision followed by wide-field
      radiotherapy. More than 4 years later there are no signs of local recurrence or
      of metastasis.

PMID- 8733387
TI  - Multiple pigmented follicular cysts: a subtype of multiple pilosebaceous cysts.
AB  - Pigmented follicular cyst is a rare disorder which typically presents as a
      pigmented papule on the head or neck and which, histologically, exhibits
      terminally differentiated, pigmented hair shafts in an epidermoid cyst. We report
      a 22-year-old man with the multiple variant of this disorder. Clinically he had
      numerous brown-blue to flesh-coloured, domed-shaped papules, on the anterior
      chest and abdomen, of 10 years duration. Histologically, hybrid cysts exhibiting
      trichilemmal and epidermoid keratinization were seen. The cysts contained
      numerous pigmented, terminally differentiated hair shafts and, embedded in the
      wall of one cyst, was a sebaceous gland. The condition of multiple pigmented
      follicular cysts, is thought to represent a distinct subtype within the spectrum
      of multiple pilosebaceous cystic disorders.

PMID- 8733390
TI  - Membranocystic changes in the panniculitis of dermatomyositis.
AB  - Clinically apparent panniculitis is rare in dermatomyositis. The common
      histopathological findings are infiltration of lymphocytes, epithelioid cells and
      plasma cells in the fat lobules, along with varying degrees of fat degeneration
      and fibrosis. We report a 65-year-old woman with dermatomyositis who developed
      panniculitis with a characteristic histological change known as a membranocystic
      lesion. Although this change has been observed in various diseases affecting the
      subcutaneous fat tissue, it has rarely been reported in dermatomyositis.
      Dermatomyositis should be included in the diseases showing a membranocystic
      lesion.

PMID- 8733389
TI  - Eosinophilic pustular folliculitis effectively treated with recombinant
      interferon-gamma: suppression of mRNA expression of interleukin 5 in peripheral
      blood mononuclear cells.
AB  - Eosinophilic pustular folliculitis (EPF) is characterized clinically by pruritic
      grouped follicular papules and pustules on the trunk, limbs, and face, and,
      histologically, by follicular infiltration with eosinophils. The blood eosinophil
      count is elevated in most patients. Oral minocycline, nonsteroidal anti
      inflammatory drugs, diaminodiphenylsulphone, and corticosteroids may induce
      remission. We report two Japanese men with EPF who responded poorly to the usual
      therapy. Intravenous injections of recombinant interferon-gamma (rIFN-gamma), 5 x
      10(5) to 2 x 10(6) Japan Reference Unit (JRU) (1 JRU roughly corresponds to 4 NIH
      units) daily for 7 days, cleared the skin lesions and returned the peripheral
      eosinophil counts to normal in both patients. However, the lesions recurred 2-3
      days after rIFN-gamma was stopped. Both patients have received intravenous rIFN
      gamma once or twice a week for nearly 1 year without systemic side-effects.
      Reverse transcriptase-polymerase chain reaction revealed a decreased expression
      of interleukin 5 (IL-5) mRNA in peripheral mononuclear cells after the rIFN-gamma
      therapy. rIFN-gamma may become the treatment of choice in recalcitrant EPF,
      although further studies are needed. It may work by interfering with the
      immunological function of type 2 T-helper cells, including IL-5 production
      responsible for the growth and differentiation of eosinophils.

PMID- 8733391
TI  - A new microemulsion formulation of cyclosporin (Neoral) is effective in the
      treatment of cyclosporin-resistant dermatoses.
AB  - Cyclosporin is a highly effective treatment for severe psoriasis and atopic
      dermatitis. However, both inter- and intrapatient gastrointestinal absorption of
      the conventional formulation of cyclosporin (Sandimmun) are very variable,
      ranging from 20 to 50%. Variations in bioavailability may explain isolated
      resistance to therapy. Neoral is a novel microemulsion formulation of cyclosporin
      which has been developed to enhance and standardize its absorption. We report the
      first experience with Neoral in patients with psoriasis and atopic dermatitis
      refractory to Sandimmun.

PMID- 8733392
TI  - Total leucoderma: a rare manifestation of cutaneous chronic graft-versus-host
      disease.
AB  - We describe a 14-year-old boy who developed total leucoderma during the course of
      chronic graft-versus-host disease, which developed after allogeneic bone marrow
      transplantation. Skin biopsy and dihydroxy-phenylalanine staining revealed a
      total absence of melanocytes from the epidermis. Cytotoxic anti-melanocyte
      antibodies were found in the patient's serum, and this probably explains the
      development of the leucoderma.

PMID- 8733393
TI  - Minocycline-induced hyperpigmentation in leprosy.
AB  - A 36-year-old man was treated with dapsone, rifampicin and clofazimine for
      borderline lepromatous leprosy. After 9 months, his leprosy plaques became
      progressively more red and after 23 months, the clofazimine was stopped and he
      was given minocycline instead. Six weeks later, he developed blue-black
      pigmentation in his leprosy lesions. The histology was consistent with
      minocycline-induced hyperpigmentation. This is the first report of minocycline
      induced pigmentation in leprosy. We suggest it is important to consider this side
      effect before the administration of minocycline in leprosy, particularly if it is
      prescribed in place of clofazimine.

PMID- 8733394
TI  - Colonic pseudo-obstruction: a complication of herpes zoster.
AB  - Herpes zoster has been associated rarely with somatic and visceral motor
      complications, including segmental motor paralysis, neurogenic bladder
      dysfunction and, unusually, colonic pseudo-obstruction. We report a patient who
      developed acute pseudo-obstruction of the colon which followed the appearance of
      dermatomal herpes zoster.

PMID- 8733395
TI  - An Epstein-Barr virus-associated lymphoproliferative lesion of the skin
      presenting as recurrent necrotic papulovesicles of the face.
AB  - We describe four patients with lymphoproliferative lesions confined to the skin
      for several years. They presented with recurrent necrotic papulovesicles of the
      face. Latent Epstein-Barr virus (EBV) infection was detected in the lymphoid
      cells from the skin lesions by in situ hybridization. The disease in three
      patients progressed to T-cell lymphoma. We believe that these patients represent
      a subset of peripheral T-cell lymphoma with a tendency to localize in the skin.

PMID- 8733396
TI  - Herpes simplex virus infection masquerading as condyloma acuminata in a patient
      with HIV disease.
AB  - Verrucous lesions in patients with human immunodeficiency virus (HIV) disease may
      be caused by viruses other than the human papillomavirus. We describe a 32-year
      old HIV-positive black man who presented with a verrucous lesion of the
      intergluteal cleft that clinically resembled condyloma acuminata or verrucous
      carcinoma. Histopathological examination revealed the changes of herpes virus
      infection, and culture of the tissue confirmed the presence of herpes simplex
      virus. Human papillomavirus was not detected by in situ hybridization or the
      polymerase chain reaction. Significant regression of the lesion was seen after 6
      weeks of treatment with oral acyclovir.

PMID- 8733397
TI  - Disseminated varioliform pustular eruption due to Mycobacterium avium
      intracellulare in an HIV-infected patient.
AB  - Severe disseminated infection due to Mycobacterium avium intracellulare, with
      unusual cutaneous features, is reported in a patient with acquired
      immunodeficiency syndrome (AIDS). The eruption appeared as disseminated pustular
      lesions which showed necrotic features and which led to varioliform scarring.
      Bacterial culture from the skin, blood, and bone marrow, and ultimately from the
      bronchoalveolar fluid and sputum, was positive for M. avium intracellulare. The
      patient was successfully treated using a multiple agent anti-mycobacterial
      regimen including clarithromycin, which appeared to be the most effective drug.
      This resulted in resolution of the cutaneous and general symptoms. Our patient
      illustrates the wide spectrum of skin presentations that may be seen with
      mycobacterial infections in subjects infected with the human immunodeficiency
      virus (HIV). Clarithromycin is an important agent for the treatment of these
      severe infections.

PMID- 8733398
TI  - Acute exanthem and pancreatic panniculitis in a patient with primary HIV
      infection and haemophagocytic syndrome.
AB  - We report a patient with an acute infection with the human immunodeficiency virus
      (HIV), who initially presented due to a mononucleosis-like illness that included
      a rash on the upper trunk and limbs, and oral ulceration. The patient developed a
      haemophagocytic syndrome with severe systemic involvement. Three weeks after the
      initial presentation, lesions of a pancreatic panniculitis appeared on both legs.

PMID- 8733399
TI  - Severity of atopic dermatitis in India.

PMID- 8733400
TI  - Anabolic steroids and psoriasis exacerbation.

PMID- 8733401
TI  - Vascular density and survival in cutaneous melanoma.

PMID- 8733402
TI  - p53 protein expression in viral warts from renal allograft recipients.

PMID- 8733403
TI  - High-dose chemotherapy with autologous stem cell transplantation in a patient
      with a CD30+ anaplastic large cell lymphoma of the skin.

PMID- 8733404
TI  - Malignant eccrine poroma in a patient with Rothmund-Thomson syndrome.

PMID- 8733405
TI  - Treatment of xeroderma pigmentosum variant with low-dose etretinate.

PMID- 8733406
TI  - 24 March--International Tuberculosis Day.

PMID- 8733407
TI  - A challenge--to our practices and to our principles.

PMID- 8733408
TI  - Respiratory effects of organic solvent exposure.
AB  - Organic solvents are widely used in industrial processes and found in many common
      household products. Exposures to solvents are common in both idustrialized and
      industrializing countries. While organic solvents exposure is well known to
      produce central nervous system toxicity, hepatic, renal and dermatologic injury,
      the respiratory effects of solvent exposure are poorly documented. Several recent
      population-based epidemiologic studies have found an independent association of
      occupational solvent exposure with respiratory symptoms, impaired pulmonary
      function or respiratory disease, but interpretation of these studies is limited
      by self-reported exposure data. Animal studies have demonstrated adverse effects
      in both the conducting and the respiratory airways, although often at very high
      exposure levels. Human chamber studies have most consistently reported irritation
      of the eyes, nose and throat without evidence of airway hyper-responsiveness.
      Case series have observed obstructive and restrictive effects in patients with
      high level inhalational exposures to solvents, particularly formaldehyde, but
      occupational epidemiologic studies have not consistently demonstrated changes in
      pulmonary function. Finally, mortality studied have not found increased mortality
      rates from respiratory disease in occupations associated with solvent use. In
      general, solvents have been demonstrated to cause mucosal irritation of the eyes
      and upper airways, but studies of pulmonary impairment following exposure have
      been limited and inconsistent. Solvent-mediated respiratory toxicity is
      biologically plausible, but further research is needed to better characterize
      exposures and to elucidate the specific mechanisms associated with injury.

PMID- 8733409
TI  - Clarithromycin against Mycobacterium avium complex infections.
AB  - The turning point in antimicrobial therapy of Mycobacterium avium infections came
      with the development of two new macrolides, clarithromycin and azithromycin.
      Controlled clinical trials, the first ever conducted with any agent among
      patients with M. avium infection, indicated the high efficiency of
      clarithromycin, in either acquired immune deficiency syndrome (AIDS) patients
      having a disseminated infection or non-AIDS patients with localized pulmonary
      disease. Monotherapy with clarithromycin resulted in elimination of bacteremia in
      almost all patients with disseminated infection, which is inevitably followed by
      a relapse of bacteremia in patients who survived long enough to reach this event.
      The strains susceptible to clarithromycin isolated before therapy contained 10(
      8) or 10(-9) resistant mutants, and the relapses of bacteremia were caused by
      multiplication of these pre-existing mutants. Clarithromycin-resistance was
      associated with a mutation in the 23S rRNA gene. Cross-resistance between
      clarithromycin and azithromycin was confirmed with laboratory mutants and
      clinical isolates. At least two methods for determining the susceptibility of the
      M. avium isolates to clarithromycin are available: one is minimum inhibitory
      concentration (MIC) determination on Mueller-Hinton agar (pH 7.4) supplemented
      with 10% Oleic acid-albumin-dextrose catalase, the other is MIC determination in
      7H12 broth, also at pH 7.4. The breakpoints for 'susceptible' for these methods
      are < or = 8.0 micrograms/ml and < or = 2.0 micrograms/ml, respectively. The
      breakpoints for 'resistant' are > 128 micrograms/ml for the agar method and >
      32.0 micrograms/ml for the broth method. The predictability value of MIC
      determination was confirmed by comparing the test results with the patients'
      clinical and bacteriological response to therapy. The remaining major problem in
      the therapy of the M. avium infections is a selection of companion drugs to be
      used in combination with clarithromycin (or azithromycin) to prevent the
      emergence of the macrolide-resistance. A number of clinical trials are now in
      progress to find a solution to this problem.

PMID- 8733410
TI  - Thiacetazone: time to call a halt? Considerations on the use of thiacetazone in
      African populations with a high prevalence of human immunodeficiency virus
      infection.

PMID- 8733412
TI  - Frequency and type of reactions to antituberculosis drugs: observations in
      routine treatment.
AB  - SETTING: United Kingdom, 1978-1992. OBJECTIVE: To assess the incidence and type
      of reactions to antituberculosis drugs in an unselected series of patients.
      DESIGN: All patients treated for tuberculosis had details of drug treatment,
      durations and side-effects requiring alteration of treatment available. The data
      was compiled retrospectively for 1978-1980 patients and prospectively thereafter.
      Analysis of drug reactions was by drug, total months drug use, by age, sex and
      ethnic group, and reaction type. RESULTS: Of 1317 patients 67 (5.1%) had 70
      reactions to antituberculosis drugs requiring modification of treatment. The
      frequency of drug reactions increased from 2.3% at age 0-19 to 4.6% at age 20-39,
      7.1% for age 40-59 and to 8.4% for those aged 60 and over. Females had
      significantly higher reactions rates than males. White patients had higher
      reaction rates than Pakistani and Indian patients, mainly due to the average age
      being greater. CONCLUSION: The drug reaction rate of 5.1% in this largely
      prospective study is lower than that reported in other unselected series in the
      UK and other countries.

PMID- 8733411
TI  - Cost-effectiveness and total costs of three alternative strategies for the
      prevention and management of severe skin reactions attributable to thiacetazone
      in the treatment of Human Immunodeficiency Virus positive patients with
      tuberculosis in Kenya.
AB  - SETTING: Severe skin reactions due to thiacetazone (T) in Human Immunodeficiency
      Virus (HIV) positive tuberculosis patients have been reported in several
      publications, one of them from Kenya. However, the abandoning of T may not be
      feasible in Kenya as this may increase the cost of drugs by about three-fold per
      regimen. OBJECTIVE: To compare the cost-effectiveness and total cost of three
      strategies in which T is replaced with ethambutol (E). DESIGN: Three strategies
      are compared with a baseline strategy in which T is not replaced. The indicator
      for cost-effectiveness is the cost-per-averted-death attributable to T. RESULTS:
      Education of patients on the possibility of side-effects and replacement of T
      with E is the most cost-effective strategy at HIV prevalence rates of 1-90%.
      Abandonment of T and replacement with E is the most cost-effective at over 90%
      HIV prevalence. CONCLUSION: In Kenya, education of patients on the possibility of
      skin reactions should be preferred at low range HIV prevalence rates. Routine HIV
      testing would be the most attractive strategy in the middle range, and total
      replacement of T with E is to be preferred in the higher range of HIV prevalence.

PMID- 8733413
TI  - A decade of experience with Mycobacterium tuberculosis culture from children: a
      seasonal influence on incidence of childhood tuberculosis.
AB  - SETTING: A tertiary care hospital in the Western Cape Province of South Africa
      from November 1983-October 1993. OBJECTIVE: Evaluation of the source of all
      cultures of Mycobacterium tuberculosis from children aged < 13 years and
      documentation of the mean time for culture with Lowenstein-Jensen (LJ) medium and
      a radiometric method (Bactec). RESULTS: One thousand six hundred and sixty
      cultures of M. tuberculosis were obtained from 1204 children (638 (53%) males and
      566 (47%) females). The median time to a positive culture result was 65 days with
      LJ medium and 23 days with Bactec (P < 0.0001). Gastric aspirate provided 1298
      cultures (78%) from 983 children (82%) of whom 52% were aged < 2 years. Ninety
      six positive sputum specimens were from 79 children (7%) of whom 70% were > 5
      years. Significantly more positive cultures were obtained during the late winter
      and early spring (P < 0.001), and a similar trend was found for tuberculous
      meningitis. CONCLUSION: The use of a radiometric culture method has expedited the
      confirmation of tuberculosis in childhood in our hospital. Even in children < 3
      months of age the diagnosis of tuberculosis can often be confirmed by culture.
      The documented increase in childhood tuberculous disease in spring suggests an
      increased transmission of tuberculous infection in autumn and winter in our
      community.

PMID- 8733414
TI  - Acute community-acquired bacterial pneumonia in Human Immunodeficiency Virus
      (HIV) infected and non-HIV-infected adult patients in Cameroon: aetiology and
      outcome.
AB  - SETTING: Yaounde Central Hospital, Jamot Hospital, Yaounde, and CEBEC Hospital in
      Douala. OBJECTIVE: To determine and compare the bacterial aetiology and outcome
      of acute community-acquired pneumonia in adult patients with and those without
      the Human Immunodeficiency Virus (HIV) infection. DESIGN: We studied 110
      consecutive adult patients admitted for pneumonia into three hospitals in
      Cameroon, from November 1991 to December 1992. Blood cultures, sputum microscopy
      and cultures as well as pneumococcal antigen detection in sera and sputum were
      performed. Serological analysis for HIV, Mycoplasma pneumoniae, Coxiella burnetti
      and Chlamydia pneumoniae was also done. RESULTS: Twenty-eight (25.5%) of the 110
      patients were HIV positive. Streptococcus pneumoniae was the most common single
      bacterial aetiology in the two groups. Bacteremia was observed in 12 (15.0%) of
      80 patients on whom blood cultures were done and was significantly more common in
      HIV seropositive than seronegative patients. Mortality was the same in the two
      groups. CONCLUSION: There were no differences in aetiology and outcome between
      HIV seropositive and seronegative patients. However, bacteremia occurred more
      significantly in the HIV seropositive group.

PMID- 8733415
TI  - Tuberculin reactivity in Bacillus Calmette-Guerin vaccinated subjects.
AB  - SETTING: The Centre for Prevention and Control of Tuberculosis in Barcelona,
      Spain, where the staff appointed to Training Centers are examined. AIMS: To check
      for tuberculin sensitivity due to Bacillus Calmette-Guerin (BCG) vaccine and
      ascertain its duration. METHOD: We compared the results of a tuberculin test (TT)
      on vaccinated and non-vaccinated subjects. The induration diameter and the time
      elapsed between BCG vaccination and the TT were determined. RESULTS: Of the 2424
      vaccinated subjects, 1489 (61.4%) reacted to TT (> or = 5 mm) and of the 3135 non
      vaccinated, 905 (28.9%) reacted, a significant difference. Of 1978 subjects
      vaccinated between 6 and 14 years of age, 63.3% were TT reactors, compared to
      23.9% of the 1948 non-vaccinated. Induration diameters > or = 15 mm amounted to
      11% for vaccinated subjects and 8% for those not vaccinated, a significant
      difference. The time from vaccination to TT was 13-25 years. Of the 446 subjects
      vaccinated at birth, 237 were reactors (53.1%); of the 887 non-vaccinated
      subjects of the same age, 154 (17.4%) reacted. Reactors > or = 15 mm amounted to
      40 (9%) for vaccinated subjects and 46 for non-vaccinated (5.2%), a significant
      difference. The time elapsed between vaccination and TT was 20-25 years. For 124
      vaccinated subjects with a previous negative TT, a second test was positive for
      87 (70.2%), and for 257 non-vaccinated it was positive for 64 (24.9%). The
      difference is due to a booster effect. CONCLUSIONS: BCG vaccination at birth and
      for school age children causes a reactivity to tuberculin which persists for 20
      to 25 years. An induration diameter of > or = 15 mm does not exclude a vaccinal
      origin. For vaccinated subjects with a previous negative TT, it is necessary to
      exclude the booster effect.

PMID- 8733416
TI  - [Results of a national tuberculosis survey carried out from 1980 to 1989 in
      Algeria].
AB  - SETTING: Algeria, where mass BCG vaccination is performed at birth, has a high
      prevalence of tuberculosis. OBJECTIVE: To measure the scale of the tuberculosis
      problem and the impact of the National Tuberculosis Control Programme set up in
      1972, a tuberculin survey was performed at regular intervals from 1980-1989 in
      Algeria. DESIGN: The survey took place in the schools of five communities of
      differing socio-economic levels. During two visits five years apart, respectively
      18,960 and 30,738 children aged 8.5 years were tested. During the second visit,
      10,301 children aged 12.5 were included in the survey. RESULTS: The prevalence of
      infection in children with no scar, non-vaccinated or whose vaccination status
      was unknown, was 4.05% in 1980-1984 and 2.71% in 1985-1989. With an annual
      decrease of 7.8%, the annual risk of tuberculosis infection was 0.34% in 1980
      1984 and 0.22% in 1985-1989. CONCLUSION: The results of the survey seem to
      indicate the continued abatement of the tuberculosis problem in the years to
      come. They also show that tuberculin surveys at regular intervals can be
      performed in high-prevalence countries where there is mass BCG vaccination at
      birth.

PMID- 8733417
TI  - Direct detection of Mycobacterium tuberculosis in sputum samples from Guinea
      Bissau by an rRNA target-amplified test system.
AB  - SETTING: There is a need for more sensitive and rapid methods for laboratory
      confirmation in the diagnosis of tuberculosis. OBJECTIVE: To investigate the
      applicability of a target rRNA amplified test system (AMTDT, Gen-Probe, CA) for
      rapid detection of Mycobacterium tuberculosis. DESIGN: The rRNA amplified test
      system was compared to standard methods for acid fast microscopy and
      mycobacterial culture for the demonstration of M. tuberculosis in sputum samples
      from 247 patients in Guinea Bissau with suspected tuberculosis. RESULTS: The
      highest incidence of positive samples was obtained with the AMTDT test. Out of
      274 sputum samples 96 (35%) were positive by the AMTDT test, 82 (30%) were
      positive by culture and 38 (14%) by direct microscopy. Using culture as reference
      method the sensitivity of the test was 85% (after discrepancy analysis 87%), and
      the specificity was 86% (after discrepancy analysis 93%). CONCLUSION: The
      sensitivity and specificity of the AMTDT test used in this setting indicates that
      it may be a valuable complement for improving the laboratory diagnosis of
      tuberculosis.

PMID- 8733418
TI  - Genetic and serovar typing of clinical isolates of the Mycobacterium avium
      intracellulare complex.
AB  - SETTING: One hundred and thirty-four Mycobacterium avium-intracellulare complex
      (MAC) isolates were obtained from 121 patients in the UK. OBJECTIVE: To compare
      serotyping and genetic analysis for species identification of MAC isolates from
      patients with and without the acquired immunodeficiency syndrome (AIDS). DESIGN:
      Clinical MAC isolates were cultured and analyzed by serotyping, the commercially
      available Accuprobe kit, hybridization with genes coding for the 19 kDa and 38
      kDa antigens of M. tuberculosis and fingerprinting with the pMB22 probe derived
      from M. paratuberculosis. RESULTS: Species classification on the basis of genetic
      analysis was similar to serovar typing, with only exceptional discrepancies.
      Serovar prevalence was different in the two groups of patients, and different
      from those reported in other countries. MAC isolates from AIDS patients were
      exclusively M. avium, whereas patients without AIDS had MAC infections with M.
      avium and M. intracellulare in about equal proportion. M. intracellulare clinical
      isolates were genetically more heterogeneous than M. avium. Only M.
      intracellulare hybridized with the 38 kDa gene probe. CONCLUSIONS: Serovars are
      strongly linked with species in clinical MAC isolates, confirming results
      previously obtained with reference strains. M. intracellulare can be easily
      identified by the presence of a 38 kDa gene.

PMID- 8733419
TI  - Association of various genetic markers with tuberculosis and other lung diseases
      in Tuvinian children.
AB  - SETTING: Heredity factors influence susceptibility to tuberculosis and other lung
      diseases. Recent immunogenetic studies have confirmed the genetic predisposition
      to lung diseases in different populations. Precise knowledge of genetic aspects
      of disease susceptibility is important for improvement of public health.
      OBJECTIVE: The aim of our research was to study the distribution of certain
      genetic markers in Tuvinian children suffering from tuberculosis and other lung
      diseases and to compare it with that in ethnically- and age-matched healthy
      donors. HLA-A, -B, -C and -DR antigens have been defined serologically by
      lymphocytotoxic assay, and variants of polymorphic protein loci Hp, Tf, Gc, ESD,
      ACP, PGM1, ADA, PGD have been defined by electrophoresis. RESULTS: It was
      demonstrated that in Tuvinian children with tuberculosis the frequencies of HLA
      DR2 and HLA-DRw53 antigens are increased in comparison with healthy donors. In
      children with non-tuberculous chronic lung diseases with allergic components the
      frequency of HLA-A1, -B5 and -B8 antigens and of genetic variants Hp2-2 and ESD1
      1 was elevated. CONCLUSION: HLA complex genetic factors influence susceptibility
      to tuberculosis and other lung diseases in Tuvinian children.

PMID- 8733420
TI  - Tuberculin skin testing and the health care worker: lessons of the Prophit
      Survey.
AB  - SETTING: Concern about occupationally-acquired tuberculosis continues to grow,
      even as control of tuberculosis in the USA has improved. Many health care workers
      have developed occupationally-acquired tuberculosis in recently described
      outbreaks and several have died. Regulatory agencies are struggling to develop a
      rational policy that promises both worker safety as well as cost-effectiveness.
      Future infection control efforts will be evaluated by results of tuberculin skin
      tests of employees. However, unlike many modern diagnostic tests, the tuberculin
      skin test is poorly understood, may be unreliable, and requires individual
      physician interpretation. DESIGN: Review of the British Prophit Survey, conducted
      from 1933-1944, which involved tuberculin testing of 10,000 young adults, with
      the goal of defining 'the relationship between tuberculin sensitivity and
      tuberculous immunity'. RESULTS: Four findings are particularly pertinent to the
      current debate: 1. job-specific rates of tuberculin conversion and subsequent
      development of disease; 2. risk of exogenous re-infection among already
      tuberculin positive health care workers; 3. rates of tuberculin skin test
      reversion; and 4. implications of induration size. CONCLUSION: The British
      Prophit Survey produced a great deal of meaningful information regarding the
      meaning of a positive tuberculin skin test, a negative test, and a change in
      tuberculin status. Proper interpretation of this test requires full appreciation
      of its many idiosyncrasies.

PMID- 8733421
TI  - Front-line management of pulmonary tuberculosis: an analysis of tuberculosis and
      treatment practices in urban Sindh, Pakistan.
AB  - SETTING: Karachi and Hyderabad, Pakistan. OBJECTIVE: To describe the level and
      quality of tuberculosis (TB) case management by non-TB control program (TCP)
      physicians in urban Sindh, Pakistan. DESIGN: We interviewed 152 adults with
      pulmonary TB confirmed by Karachi's TB control program regarding the initial
      management of their TB symptoms before entering the TCP. We also surveyed 65
      general practitioners (GPs) attending continuing education seminars with a
      multiple choice test to assess their management of suspected pulmonary TB. We
      compared both results to guidelines from the World Health Organization (WHO) and
      the International Union Against Tuberculosis and Lung Disease (IUATLD). RESULTS:
      Eighty percent (122/152) of patients first sought GPs. Only 14% of GPs performed
      any sputum test. At most, 17 (40%) of the 42 patients recalling their GP's
      treatment, received the recommended 4-drug regimen. However, 68% (45/65) of
      surveyed GPs chose correct treatment from a multiple choice format. But their
      initial laboratory investigations, follow-up, and treatment cessation criteria
      (9%, 9-31%, and 11% correct, respectively) demonstrated under-utilization of
      sputum tests and over-reliance on unhelpful tests. CONCLUSIONS: GPs first saw
      most of these TCP patients, but their weak management likely hinders TB control.
      A partnership between TB control programs and GPs could improve case management
      and hasten TB control.

PMID- 8733422
TI  - Short-course therapy of pulmonary tuberculosis: doctor's compliance.
AB  - OBJECTIVE: The present study, conducted from 1986 to 1991, investigated the
      accuracy of treatment monitoring performed by practitioners in the out-patient
      treatment of pulmonary tuberculosis. DESIGN: All patients with smear or culture
      positive pulmonary tuberculosis, receiving 6-month short-course chemotherapy with
      Isoniazid (H), Rifampicin (R) and Pyrazinamide (Z), were included. Treatment had
      been initiated either in our unit, or shortly before, with discharge after an
      average time of 8 weeks. Practitioners were sent a flow sheet advising how to
      perform standardized ambulatory controls. RESULTS: Forty-three patients were
      included in the study, four of whom did not visit their practitioner after
      discharge. It must be assumed that they did not complete treatment. The average
      follow-up time of the remaining 39 patients was 159 weeks. In 13 cases the
      treatment was prolonged without obvious reason. For four patients who had not
      converted to a negative sputum culture at discharge, negativity was never been
      proven thereafter. Objective means of assessing patient compliance by H-urine
      strip testing were undertaken only in three cases. X-ray controls were performed
      adequately in 44.4% of the cases. By contrast monthly checks of liver enzymes had
      been done only in 23.1% of the patients. CONCLUSION: We conclude that even a
      highly standardized protocol of short-course tuberculosis treatment requires a
      certain level of experience and compliance on the part of the practitioner. We
      accordingly recommend that every case of pulmonary tuberculosis should be
      reviewed at least twice by a chest physician.

PMID- 8733423
TI  - Humoral immune response in infants after Bacillus Calmette-Guerin (BCG)
      vaccination.

PMID- 8733424
TI  - Unusual multiple tuberculomas of the bilateral lung -letter-.

PMID- 8733425
TI  - A pilot study of antituberculous combination comparing rifabutin with rifampicin
      in the treatment of Human Immunodeficiency Virus-1 associated tuberculosis.

PMID- 8733426
TI  - Rifabutin-containing regimens for pulmonary tuberculosis: early assessment of
      treatment effectiveness.

PMID- 8733428
TI  - Kinetic constraints in acute aluminium toxicity in the rainbow trout
      (Oncorhynchus mykiss).
AB  - We have designed a laboratory bioassay to expose fish to kinetically determined
      differences in aluminium hydroxide solution chemistry. We have used this system
      to demonstrate the hitherto unexpected result of an acute aluminium toxicity in
      the fish at a pH of 6.5. Supporting experiments have demonstrated that the
      mechanism of toxicity at this pH was probably an asphyxiation brought about by
      aluminium-induced changes in the rheological and diffusional properties of the
      mucus lining of the gill epithelium.

PMID- 8733427
TI  - Spatial heterogeneity in epidemic models.
AB  - Spatial heterogeneity is believed to play an important role in the persistence
      and dynamics of epidemics of childhood diseases because asynchrony between
      populations within different regions allows global persistence, even if the
      disease dies out locally. A simple multi-patch (metapopulation) model for spatial
      heterogeneity in epidemics is analysed and we examine conditions under which
      patches become synchronized. We show that the patches in non-seasonal
      deterministic models often oscillate in phase for all but the weakest between
      patch coupling. Synchronization is also seen for stochastic models, although
      slightly stronger coupling is needed to overcome the random effects. We
      demonstrate that the inclusion of seasonal forcing in deterministic models can
      lead to the maintenance of phase differences between patches. Complex dynamic
      behaviour is observed in the seasonally forced spatial model, along with the
      coexistence of many different behaviours. Compared to the non-spatial model,
      chaotic solutions are observed for weaker seasonal forcing; these solutions have
      a more realistic minimum number of infectives.

PMID- 8733429
TI  - An alternative model for cell sheet migration on fibronectin during heart
      formation.
AB  - The emergence of animal form and function depends on cell migrations in the
      embryo. Some migrations are accomplished by cells individually, and the mechanism
      of movement is predictable by contemporary models of cell adhesion and
      cytoskeletal function. However, other migrations occur that involve layers or
      sheets of cells connected by junctions, and the mechanism of migration is
      obscure. An example is the precardiac mesoderm, an epithelium that migrates
      anteriorly and ventrally in the early amniote embryo to the position of heart
      formation. It moves upon and is influenced by the adjacent endoderm, which has
      produced an extracellular matrix. The matrix contains the cell adhesion and
      cytoskeleton-activating glycoprotein fibronectin. Some immunolocalization studies
      have reported that fibronectin is arrayed in an anterior-to-posterior gradient,
      and it has been suggested that directional migration results from a haptotactic
      response of each cell to the gradient, a model derived from and supported by
      experiments with individual cells in culture. However, we have produced evidence
      from immunostaining that suggests fibronectin is arrayed as a localized anterior
      patch rather than a gradient. We propose an alternative model for precardiac
      epithelial migration in which only the anterior cells attach effectively to
      fibronectin. Thus adhered, their cytoskeletal contractile activity generates
      force which propagates throughout the layer of connected cells, and efficiently
      pulls them in the proper direction, following the bending and extending movements
      of the foregut, notochord and other structures of the head. Theoretical
      implications of the two models are discussed.

PMID- 8733430
TI  - A maximum-likelihood estimator of the genetic identity between polyploid species.
AB  - Based on a recently proposed method for estimating the genetic identity between
      polyploid species, maximum-likelihood estimators are given for the genetic
      identity between polyploid species, for the ancestral degree of homozygosity and
      their variances. As an example, the genetic identity, the ancestral degree of
      homozygosity and their variances were estimated from data sets of populations of
      two species, the weevil Polydrusus mollis and the salamander Ensatina complex. It
      was found that other indices of the genetic identity between species obviously
      underestimate genetic identity due to the pooling of differences caused by
      mutation and drift.

PMID- 8733431
TI  - Linear electric traction as an alternative model of the actin/myosin motor.
AB  - Current models for the action of linear biological motors may be grouped in two
      main categories. The conventional "bind and bend" models rely for their power
      stroke upon a structural change in the myosin headgroup (S1 fragment) which
      follows the binding of myosin to the F-actin filament. The more recent ratchet
      models demonstrate that directional motion of a particle along an asymmetrical
      ratchet is possible with a symmetrical but time-correlated stochastic drive. In
      this paper a new type of model is introduced which is deterministic like the
      "bind and bend" model but it requires no molecular structural changes to power
      the stroke. Like the ratchet models the motor is driven along the linear stator
      by tangential forces at the interface but the forces are electrostatic and
      controlled by the hydrolysis of ATP to ADP.

PMID- 8733432
TI  - Population evolution on a multiplicative single-peak fitness landscape.
AB  - A theory for evolution of either gene sequences or molecular sequences must take
      into account that a population consists of a finite number of individuals with
      related sequences. Such a population will not behave in the deterministic way
      expected for an infinite population, nor will it behave as in adaptive walk
      models, where the whole of the population is represented by a single sequence.
      Here we study a model for evolution of population in a fitness landscape with a
      single fitness peak. This landscape is simple enough for finite size population
      effects to be studied in detail. Each of the N individuals in the population is
      represented by a sequence of L genes which may either be advantageous or
      disadvantageous. The fitness of an individual with k disadvantageous genes is Wk
      = (1-s)k, where s determines the strength of selection. In the limit L-
      >infinity, the model reduces to the problem of Muller's Ratchet: the population
      moves away from the fitness peak at a constant rate due to the accumulation of
      disadvantageous mutations. For finite length sequences, a population placed
      initially at the fitness peak will evolve away from the peak until a balance is
      reached between mutation and selection. From then on the population will wander
      through a spherical shell in sequence space at a constant mean Hamming distance
      <k> from the optimum sequence. We give an approximate theory for the way <k>
      depends on N, L, s, and the mutation rate u. This is found to agree well with
      numerical simulation. Selection is less effective on small populations, so <k>
      increases as N decreases. Our simulations also show that the mean overlap between
      gene sequences separated by a time of t generations is of the form Q(t) = Q
      infinity + (Q0-Q infinity)exp(-2ut), which means that the rate of evolution
      within the spherical shell is independent of the selection strength. We give a
      simplified model which can be solved exactly for which Q(t) has precisely this
      form. We then consider the limit L-->infinity keeping U = uL constant. We suppose
      that each mutation may be favourable with probability p, or unfavourable with
      probability 1-p. We show that for p less than a critical value pc, the population
      decreases in fitness for all values of U, whereas for pc < p < 1/2, the
      population increases in fitness for small U and decreases in fitness for large U.
      In this case there is an optimum non-zero value of U at which the fitness
      increases most rapidly, and natural selection will favour species with non-zero
      mutation rates.

PMID- 8733433
TI  - A possible role of adenylate metabolism in human erythrocytes: simple
      mathematical model.
AB  - A simplified mathematical model of cell metabolism describing ion pump,
      glycolysis and adenylate metabolism was developed and investigated in order to
      clarify the functional role of the adenylate metabolism system in human
      erythrocytes. The adenylate metabolism system was shown to be able to function as
      a specific regulatory system stabilizing intracellular ion concentration and,
      hence, erythrocyte volume under changes in the permeability of cell membrane.
      This stabilization is provided via an increase in adenylate pool in association
      with ATPases rate elevation. Proper regulation of adenylate pool size might be
      achieved even in the case when AMP synthesis rate remains constant and only AMP
      degradation rate varies. The best stabilization of intracellular ion
      concentration in the model is attained when the rate of AMP destruction is
      directly proportional to ATP concentration and is inversely proportional to AMP
      concentration. An optimal rate of adenylate metabolism in erythrocytes ranges
      from several tenths of a percent to several percent of the glycolytic flux. An
      increase in this rate results in deterioration of cell metabolism stability.
      Decrease in the rate of adenylate metabolism makes the functioning of this
      metabolic system inefficient, because the time necessary to achieve stabilization
      of intracellular ion concentration becomes comparable with erythrocyte life span.

PMID- 8733434
TI  - Myosin heads in solution: how to interpret the data obtained by means of x-ray
      and neutron scattering?

PMID- 8733435
TI  - A unifying hypothesis for the mechanism of NSAID related gastrointestinal
      toxicity.

PMID- 8733436
TI  - Post-traumatic leg ulcer.

PMID- 8733437
TI  - Can methotrexate be used as a steroid sparing agent in the treatment of
      polymyalgia rheumatica and giant cell arteritis?
AB  - OBJECTIVE: To investigate whether methotrexate (MTX) has a steroid sparing effect
      in the treatment of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA).
      METHODS: We carried out a randomised double blind, placebo controlled study in 40
      patients with PMR, six of whom also had clinical symptoms of GCA. A temporal
      artery biopsy specimen was available from 37 patients; GCA was found in six of
      the specimens. Among the six patients with clinical signs of GCA, three had a
      positive biopsy specimen. All patients were started on prednisone 20 mg/day,
      irrespective of clinical signs and biopsy result, supplemented with a weekly,
      blinded capsule containing either MTX 7.5 mg or placebo. The prednisone dose was
      decreased as soon as clinical symptoms disappeared and erythrocyte sedimentation
      rate, C reactive protein level, or both, had normalised. RESULTS: Twenty one
      patients were followed for two years, or at least one year after discontinuing
      medication. No differences were found between the MTX group and the placebo group
      concerning time to achieve remission, duration of remission, number of relapses,
      or cumulative prednisone doses. After 21 weeks the mean daily prednisone dose was
      reduced by 50%. Forty percent of all patients were able to discontinue prednisone
      within two years. Median duration of steroid treatment was 47.5 weeks (range 3
      104). No serious complications from GCA were encountered. CONCLUSIONS: With a
      (rapid) steroid tapering regimen, it was possible to reduce the mean daily
      prednisone dose by 50% in 21 weeks and to cease prednisone in 40% of the patients
      within two years. With this regimen, no steroid sparing effect of MTX in a dosage
      of 7.5 mg/week was found.

PMID- 8733438
TI  - Incidence of ovarian failure in systemic lupus erythematosus after treatment with
      pulse cyclophosphamide.
AB  - OBJECTIVE: To investigate the incidence of ovarian failure after pulse
      cyclophosphamide treatment in systemic lupus erythematosus (SLE) and to compare
      this with two control groups: SLE patients treated with azathioprine, and a
      healthy age matched population. METHODS: All women patients with SLE treated with
      pulse cyclophosphamide in our department were identified and questioned
      concerning menstrual history. All the hospital notes were reviewed and details
      recorded on dose of cyclophosphamide, duration of treatment, side effects and
      lowest pretreatment neutrophil and leucocyte counts during the course of
      treatment. Disease controls were recruited from our department and healthy
      controls from the local family health services authority (FHSA) register.
      RESULTS: Incidence of ovarian failure in the premenopausal cyclophosphamide
      treated group was 54% and the incidence of premature menopause (occurring before
      age 40 years) was 41%. Increasing age at start of treatment showed a linear trend
      with incidence of ovarian failure (p = 0.01). Using logistic regression,
      increasing duration of treatment was related to incidence of ovarian failure (p =
      0.047 in those treated age 35 years or younger). An association between the
      lowest neutrophil count throughout the treatment period, when taken immediately
      before each planned cyclophosphamide pulse, and the incidence of ovarian failure
      was also demonstrated (p = 0.04 in those treated before age 40 years).
      CONCLUSION: Ovarian failure--in particular, premature failure after treatment
      with pulse cyclophosphamide--is common. Factors associated with increased risk
      include greater age at start of treatment, longer period of treatment, and
      greater degree of marrow suppression as assessed by the neutrophil count
      immediately before each planned cyclophosphamide pulse.

PMID- 8733439
TI  - Plasminogen activators and their inhibitors in synovial fluids from normal,
      osteoarthritis, and rheumatoid arthritis knees.
AB  - OBJECTIVES: To establish baseline concentrations of plasminogen activators and
      their inhibitors in normal knee synovial fluids, and to compare them with well
      characterised osteoarthritis (OA) and rheumatoid arthritis (RA) knee fluids.
      METHODS: A total of 26 normal subjects, 71 patients with OA, and 17 patients with
      RA underwent knee aspiration. Patients with OA were subclassified according to
      presence of nodal generalised OA (NGOA) and synovial fluid calcium pyrophosphate
      crystals. Clinical assessment of inflammation (graded 0-6) was undertaken in OA
      and RA patients. Plasminogen activator (PA), plasminogen activator inhibitor
      (PAI), and urokinase-type PA receptor (uPAR) antigen concentrations were
      determined by enzyme linked immunosorbent assay. The species of PAs present were
      determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis.
      RESULTS: Concentrations of all antigens (uPA, tissue-type PA (tPA), uPAR, and PAI
      1), were significantly greater in RA than OA; those in OA were significantly
      greater than normal. The concentrations showed no direct association with
      clinically assessed inflammation of the knee. In normal fluids, no associations
      with age were observed. Antigen concentrations (uPA, tPA, and uPAR) in NGOA
      differed from those in other subclasses of OA, but the species of PA present did
      not appear to vary between disease groups. The predominant PA appeared to have
      identity with uPA. CONCLUSION: Because of the greater concentrations of these
      antigens in OA compared with normal fluids, OA cannot be used as a surrogate
      normal control in studies of the PA/PAI system. Alteration of the PA/PAI system
      was confirmed in RA and OA knee fluids, with greater changes evident in RA. The
      finding of different concentrations of PA antigens in NGOA compared with other OA
      fluids further supports a different pathogenic mechanism in this subset.

PMID- 8733440
TI  - Divergent effects of methotrexate on the clonal growth of T and B lymphocytes and
      synovial adherent cells from patients with rheumatoid arthritis.
AB  - OBJECTIVE: To define the mechanisms whereby methotrexate (MTX) manifests its
      effects in patients with rheumatoid arthritis. METHODS: T and B cells from
      peripheral blood and rheumatoid synovial tissues, synovial adherent cells, and
      the human fibrosarcoma cell line HT1080 and its mutant (defective in an enzyme in
      the nucleotide salvage pathway) were tested for clonal growth when cultured with
      MTX. Normal human fibroblasts and those with a deficiency in a salvage pathway
      were cultured with MTX in the presence or absence of purine and pyrimidine bases.
      RESULTS: Clonal growth of T and B cells, but not synovial cells, was inhibited by
      clinically relevant concentrations of MTX. Slowly proliferating fibroblast lines
      were resistant to MTX, whereas their rapidly proliferating counterparts were not.
      However, mutant fibroblast lines deficient in a salvage pathway were sensitive to
      MTX despite slow proliferation. Similarly, while skin fibroblasts were resistant
      to MTX, germline mutant fibroblasts deficient in a salvage pathway were sensitive
      to small concentrations of MTX. CONCLUSION: T and B lymphocytes, but not synovial
      cells, may be the target of MTX in vivo. Resistance to MTX may be associated with
      slow proliferation and the ability to synthesise nucleotides via salvage
      pathways. MTX can inhibit proliferation of even slowly growing cells by
      restricting the supply of nucleotides obtained via a salvage pathway, by removal
      of purine and pyrimidine bases, or by inducing a deficiency in a salvage pathway.
      It may be possible to manipulate the therapeutic effect of MTX by adjusting the
      amounts of purines and pyrimidines available to the cells in vivo.

PMID- 8733441
TI  - Serum p55 and p75 tumour necrosis factor receptors as markers of disease activity
      in juvenile chronic arthritis.
AB  - OBJECTIVE: To determine the expression of tumour necrosis factor alpha (TNF
      alpha) and its soluble receptors (p55 and p75) in the sera and synovial fluid of
      patients with juvenile chronic arthritis (JCA), and their correlation with
      disease activity parameters. METHODS: Ninety eight sera from 45 patients with JCA
      (14 systemic, 12 polyarticular, 19 pauciarticular), 20 sera from age matched
      healthy controls, and five synovial fluids from five antinuclear antibody (ANA)
      positive pauciarticular JCA patients were tested for the presence of TNF alpha,
      soluble TNF receptors p55 and p75 (sTNFRp55, sTNFRp75), and interleukin-6 (IL-6)
      by an enzyme amplified sensitivity immunoassay. Physician global estimate of
      disease activity, weekly fever score and joint score, C reactive protein (CRP),
      erythrocyte sedimentation rate (ESR), and haemoglobin concentration were
      evaluated as parameters of disease activity. The expression of p55 and p75 on
      peripheral mononuclear cells (MNCs) from five patients with systemic JCA and
      synovial MNCs from five ANA positive patients with pauciarticular JCA was
      evaluated by flow cytometry. RESULTS: TNF alpha serum concentrations did not
      differ significantly between the patients with active JCA and the control group.
      No correlation was found between TNF alpha and parameters of disease activity,
      but both p55 and p75 showed a significant positive correlation with the physician
      global estimate of disease activity (p < 0.001), ESR (p < 0.001), CRP (p <
      0.001), and serum concentrations of IL-6 (p < 0.001). Serum concentrations of
      haemoglobin correlated inversely with the concentrations of p55 and p75 (p <
      0.001). Synovial lymphocytes selectively expressed the p75 surface receptor.
      CONCLUSIONS: sTNFRp55 and sTNFRp75 each represent a sensitive marker of disease
      activity in JCA. Their increased expression in biological fluids may support the
      hypothesis that TNF alpha has a role in the pathogenesis of JCA.

PMID- 8733442
TI  - Impaired activity of protease inhibitors towards neutrophil elastase bound to
      human articular cartilage.
AB  - OBJECTIVE: To investigate the effects of protease inhibitors on the ability of
      free and cartilage bound neutrophil elastase to degrade cartilage proteoglycan in
      vitro. METHODS: Cryostat sections of human articular cartilage were used as
      substrate, and proteoglycan loss induced by free or cartilage bound elastase was
      quantified by alcian blue staining, followed by scanning and integrating
      microdensitometry. RESULTS: High molecular mass protease inhibitors (alpha 1
      protease inhibitor, alpha 2 macroglobulin, and soya bean trypsin inhibitor) and
      synovial fluid from patients with rheumatoid arthritis were effective in blocking
      proteoglycan loss from sections treated with free elastase, but their activity
      towards cartilage bound elastase was much reduced. In contrast, low molecular
      mass elastase inhibitors (N-methoxysuccinyl-Ala-Ala-Pro-Val chloromethyl ketone
      and ONO-5046 (N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulphonylamino]benzoyl]
      amino-acetic acid) were effective against free and cartilage bound elastase.
      CONCLUSION: The binding of elastase to cartilage appears to be a mechanism
      whereby the enzyme can remain active in the presence of high molecular mass
      protease inhibitors.

PMID- 8733443
TI  - Decreased birefringence of the superficial zone collagen network in the canine
      knee (stifle) articular cartilage after long distance running training, detected
      by quantitative polarised light microscopy.
AB  - OBJECTIVE: To investigate the effects of a one year programme of running training
      (up to 40 km/day for 15 weeks) on the spatial orientation pattern of collagen and
      glycosaminoglycans in articular cartilage in different parts of the knee (stifle)
      and shoulder joints of young beagle dogs. METHODS: Area specific measurements of
      the optical path difference (= retardation, gamma) and the cartilage zone
      thickness were performed using conventional procedures and a new computer based
      quantitative polarised light microscopy method. Transmission electron microscopy
      was used to determine the zonal volume density of collagen fibrils. The
      concentrations of collagen and hydroxypyridinium crosslinks were investigated
      biochemically. RESULTS: Running training decreased gamma by 24-34% (p < 0.05) in
      the superficial zone of the lateral femoral condyle articular cartilage and at
      the centre of the tibial condyles. Gamma of glycosaminoglycans decreased by 26%
      (p < 0.05) in the superficial zone of the lateral condyle of the femur, but at
      the same site the volume density of collagen fibrils was unchanged. Neither the
      collagen concentration nor the concentration of hydroxypyridinium crosslinks was
      altered as a result of running. In both control and runner dogs, the thickness
      and gamma values of the superficial zone were greater in the humerus and the
      femur than in the tibia. CONCLUSION: Endurance type running exercise in beagles
      caused a reduction in the superficial zone birefringence of the articular
      cartilage, which indicates either a disorganisation or a reorientation of the
      superficial zone collagen network. Articular cartilage showed marked variability
      of collagen network organisation over the different knee (stifle) joint articular
      surfaces.

PMID- 8733444
TI  - How effective is therapeutic ultrasound in the treatment of heel pain?
AB  - OBJECTIVES: To evaluate the therapeutic effect from ultrasound in the treatment
      of plantar heel pain by physiotherapists and podiatrists, and to quantify the
      placebo effect of this electrophysical agent. METHODS: Patients experiencing
      episodes of plantar heel pain were allocated randomly, at each episode, to
      receive either true ultrasound (machine calibrated to deliver a dose of
      ultrasound at 0.5 w/cm2, 3 MHz, pulsed 1:4), for eight minutes, or sham
      ultrasound (only the timer on the machine activated). Each episode was treated,
      according to randomisation, eight times. An independent observer set the
      equipment before obscuring the control panel with a drape. All treatments were
      undertaken by the same operator. Patients' pain scores were measured on a 10 cm
      linear analogue scale before the course of eight treatments commenced and at the
      end of the course, and analysed using a Wilcoxon Signed-Ranks test. RESULTS:
      Nineteen patients experienced episodes of heel pain (seven bilateral). Both
      groups showed a reduction in pain; the improvement was 30% in the treated group
      and 25% in the placebo group (p = 0.5). CONCLUSIONS: Therapeutic ultrasound at a
      dosage of 0.5 w/cm2, 3 MHz, pulsed 1:4, for eight minutes is no more effective
      than placebo in the treatment of plantar heel pain.

PMID- 8733445
TI  - HLA class I associations of ankylosing spondylitis in the white population in the
      United Kingdom.
AB  - OBJECTIVE: To investigate the HLA class I associations of ankylosing spondylitis
      (AS) in the white population, with particular reference to HLA-B27 subtypes.
      METHODS: HLA-B27 and -B60 typing was performed in 284 white patients with AS.
      Allele frequencies of HLA-B27 and HLA-B60 from 5926 white bone marrow donors were
      used for comparison. HLA-B27 subtyping was performed by single strand
      conformation polymorphism (SSCP) in all HLA-B27 positive AS patients, and 154 HLA
      B27 positive ethnically matched blood donors. RESULTS: The strong association of
      HLA-B27 and AS was confirmed (odds ratio (OR) 171, 95% confidence interval (CI)
      135 to 218; p < 10(-99)). The association of HLA-B60 with AS was confirmed in HLA
      B27 positive cases (OR 3.6, 95% CI 2.1 to 6.3; p < 5 x 10(-5)), and a similar
      association was demonstrated in HLA-B27 negative AS (OR 3.5, 95% CI 1.1 to 11.4;
      p < 0.05). No significant difference was observed in the frequencies of HLA-B27
      allelic subtypes in patients and controls (HLA-B*2702, three of 172 patients v
      five of 154 controls; HLA-B*2705, 169 of 172 patients v 147 of 154 controls; HLA
      B*2708, none of 172 patients v two of 154 controls), and no novel HLA-B27 alleles
      were detected. CONCLUSION: HLA-B27 and -B60 are associated with susceptibility to
      AS, but differences in HLA-B27 subtype do not affect susceptibility to AS in this
      white population.

PMID- 8733446
TI  - Should the MHAQ ever be used?

PMID- 8733447
TI  - Epidemiology of adult Still's disease.

PMID- 8733448
TI  - Racial variation in rheumatoid arthritis.

PMID- 8733449
TI  - A double-blind comparative study of ofloxacin otic drops versus neomycin
      polymyxin B-hydrocortisone otic drops in the medical treatment of chronic
      suppurative otitis media.
AB  - Active chronic suppurative otitis media poses a management problem when patients
      are being considered for surgical treatment. Topical antibiotics have
      demonstrated varying degrees of success in the management of discharging ears.
      The introduction of quinolones has revived interest in these topical agents. This
      double-blind study compares two antibiotics, namely ofloxacin and neomycin
      polymyxin B, with similar in vitro sensitivities to Gram positive and Gram
      negative organisms. Fifty-two patients were selected randomly and the results
      show that ofloxacin eardrops have marginal benefits in symptomatic improvement
      (89 per cent versus 79 per cent, p = 0.27) and bacterial eradication (81 per cent
      versus 75 per cent, p = 0.81) in active chronic suppurative otitis media.
      Significantly fewer patients (seven per cent versus 29 per cent, p = 0.04) in the
      ofloxacin group had active disease at the end of the two-week treatment. We
      recommend the use of ofloxacin eardrops in managing active chronic suppurative
      otitis media since it has high clinical efficacy, contains no steroid component
      and has no demonstrated risk of ototoxicity.

PMID- 8733450
TI  - Effect of aerobic bacteriology on the clinical presentation and treatment results
      of chronic suppurative otitis media.
AB  - The effect of aerobic bacteriology on the clinical presentation, complications of
      the disease and long-term results of surgical treatment was assessed in a cohort
      of 368 patients with chronic suppurative otitis media. Bacteriological findings
      showed no significant difference between child and adult patients. Staphylococcus
      aureus was isolated in cholesteatoma ears more frequently than Pseudomonas
      aeruginosa, in chronic ears without cholesteatoma the situation was reversed.
      Bacteriological findings had no significant effect on the incidence of
      complications caused by the disease. Failures after surgical treatment were most
      common in Pseudomonas ears. The bacteriology had no significant effect on pre
      operative hearing levels nor post-operative hearing results. It was concluded
      that, in order to improve results of chronic ear surgery, more attention should
      be paid to pre-operative conservative treatment of chronically discharging ears,
      especially those infected by P. aeruginosa.

PMID- 8733452
TI  - Intra-operative image guidance in otolaryngology--the use of the ISG viewing
      wand.
AB  - The ISG viewing wand is an intra-operative guidance system with a proprioceptive
      robotic-like jointed arm. It provides surgeons with almost instantaneously
      reconstructed computer-generated CT or MRI images in two or three dimensions and
      can correlate any point within the operative field to its corresponding locus on
      the reformatted scan images. In addition to having been used in over 400
      neurosurgical patients in Bristol, 14 patients with skull-base, cerebello-pontine
      angle or temporal bone lesions have also undergone wand-guided resections. The
      wand has proved to be particularly useful in pre-operative planning, allowing
      minimally-invasive incisions, providing per-operative navigation, identifying the
      relationship and proximity of important anatomical structures and in assessing
      the extent of lesion resection. We illustrate the advantages of intra-operative
      image-guidance by discussing four cases. The potential applications of this form
      of imaging technology to other otolaryngological procedures are discussed.

PMID- 8733451
TI  - Glycerol and ichthammol: medicinal solution or mythical potion?
AB  - Glycerol and ichthammol (G & I) has been used for generations by otologists.
      However, there is a paucity of information on both its mode of action and its
      anti-bacterial properties. The aim of this paper was to ascertain firstly, what
      the most common organisms found in discharging ears were and secondly, what
      antibacterial activity G & I had against these organisms. All ear swabs from 1992
      1994 in our unit were reviewed to ascertain the prevalence of the commonly
      isolated organisms. Fresh isolates of these organisms were collected and plated
      onto agar with wells of glycerol, ichthammol and a combination of both as used in
      clinical practice. The diameters of the zones of inhibition observed after
      incubation were measured in millimetres. Common isolates were: Pseudomonas
      aeruginosa, Staphylococcus aureus, Proteus mirabalis, Streptococcus pyogenes in
      descending order of frequency. Pure glycerol showed no significant zones of
      inhibition against any of the organisms tested. The average zones of inhibition
      for G & I and ichthammol alone were for Staphylococcus aureus 15 mm and 18 mm and
      for Streptococcus pyogenes: 16 mm and 23 mm. Ichthammol alone was significantly
      more effective than G & I (p < 0.001). There was no significant activity against
      Proteus mirabalis and Pseudomonas aeruginosa. The therapeutic benefit of G & I is
      due in part to the inherent anti-bacterial activity of ichthammol against the
      Gram positive organisms as well as its anti-inflammatory action and the
      dehydrating effect of the glycerol.

PMID- 8733453
TI  - Craniometaphyseal and craniodiaphyseal dysplasia, head and neck manifestations
      and management.
AB  - Craniometaphyseal and craniodiaphyseal dysplasia are rare genetic disorders of
      bone due to modelling errors of long bones and skull bones. These syndromes
      present with multiple ENT symptomatology from an early age. The diagnostic
      distinction can now be made radiologically by serial skeletal survey which is
      important for prognosis. We review the clinical, radiological, computed
      tomography (CT) scan, otological, audiological and histopathological findings in
      two cases with craniodiaphyseal, and two cases with craniometaphyseal dysplasia,
      and report our experiences of medical and surgical treatment to date. In the
      craniodiaphyseal dysplasia, the hearing abnormality progressed from an initial
      conductive to a mixed loss on serial audiometric follow up. Temporal bone CT
      scans showed narrowing of the middle ear cavity, internal auditory meatus, and
      facial nerve canal at the geniculate ganglion. Benefits from choanal stenosis
      surgery, craniofacial remodelling and dacrocystorhinostomy were shortlived.
      Calcitriol therapy with a low calcium diet did not alter the clinical course of
      progression in our cases. The underlying defect, causing net bone formation in
      these phenotypically similar syndromes, appears to be different when based on the
      differing biochemical responses to calcitriol and bone biopsy findings. Increased
      numbers of osteoblasts were found in bone biopsies from both cases with
      craniodiaphyseal dysplasia. Early recognition is crucial in these conditions as
      therapy directed at the underlying bony defect has the best chance of success if
      initiated in infancy.

PMID- 8733454
TI  - Immunoglobulin-coated bacteria on the tonsillar surface during infectious
      mononucleosis.
AB  - Sequential bacterial samples were obtained from the tonsillar surface of 19
      consecutive patients (12 females, seven males; mean age 16.1 years, range four to
      24 years) suffering from infectious mononucleosis with membranous tonsillitis.
      The specimens were examined with respect to aerobes (culture on blood and
      chocolate agar plates) and proportions of bacteria coated with immunoglobulins
      (secretory IgA, IgG, IgM) by using an immunofluorescence assay. In the early
      stage of the membranous tonsillitis phase, attachment of secretory IgA (SIgA) and
      IgG to the bacteria was greatly suppressed, as compared with healthy controls.
      Coating with IgM was evident only late in the membranous tonsillitis phase but
      was contracted and still evident even after the clinical throat symptoms had
      abated. The findings suggest that the B-lymphotropic Epstein-Barr virus,
      causative agent of infectious mononucleosis, exerts a transient suppression of
      immunoglobulin-coating of bacteria harboured on the tonsillar surfaces, with
      consequent abundant bacterial attachment to the epithelial cells and massive
      bacterial colonization on the palatine tonsils.

PMID- 8733455
TI  - Speech assessment of patients using three types of indwelling tracheo-oesophageal
      voice prostheses.
AB  - A multidisciplinary prospective study compared speech acceptability between three
      types of indwelling tracheo-oesophageal voice prostheses. Twenty male
      laryngectomees took part over five years, using 42 prostheses. Speech was
      assessed on a discrete scale by trained and untrained personnel. The majority
      scored in the mid-range for each assessor. The kappa coefficient was used to test
      similarity between assessors, and for all pairings agreement was significant (p <
      0.05). The speech and language therapist tended to give higher scores and the
      patient lower. A relationship was found between patients' ages categorized by
      decade and the surgeon's score alone. This relationship held for Groningen high
      resistance and Provox prostheses individually too (p < 0.05). The untrained
      assessed similarly to the professionals--humans are all voice listeners. The
      analysis suggests surgeons find tracheo-oesophageal speech in older patients
      better than in younger ones; or make more allowances for the elderly. There was a
      trend for Provox prostheses to produce the best scores.

PMID- 8733456
TI  - Value of lymph node biopsy in the diagnosis of acquired toxoplasmosis.
AB  - Toxoplasmic lymphadenitis generally involves a solitary lymph node in the head
      and neck regions, without systemic symptoms. In order to determine the frequency
      of toxoplasmic lymphadenitis, we reviewed the histological sections of 731
      consecutive patients with reactive lymph node hyperplasia. Amongst 731 patients,
      112 had histological features supporting a diagnosis of toxoplasmic lymphadenitis
      (15.3 per cent). In 80 of these patients (71 per cent), either Indirect
      Haemaglutination test (IHA), in 37 cases, or the Enzyme-Linked Immunosorbent
      Assay (ELISA) for detecting toxoplasmic IgG or IgM antibodies, in 43 cases, were
      performed. In 76 out of 80 patients (95 per cent), histological features
      correlated well with serological studies. The IHA test was positive in 30
      patients with a titre of 1/64 or higher. The IgG-ELISA test was positive in 11
      whereas the IgM-ELISA test was positive in 28 patients. These results provide
      further evidence of the distinctive nature of the histological changes in
      toxoplasmic lymphadenitis, which should enable the clinician to make a confident
      diagnosis of acute acquired toxoplasmosis.

PMID- 8733457
TI  - Unknown primary of the head and neck.
AB  - The occurrence of metastases to the cervical lymph nodes from an unknown primary
      tumour is seen in approximately three to six per cent of patients with cervical
      adenopathy and the primary tumour commonly remains elusive. Single modality
      treatment is occasionally advocated but combined treatment seems to obtain the
      best results. A retrospective analysis of patients' charts with unknown primary
      of the head and neck in the University of Michigan Medical Center was undertaken
      for the years 1978-1992. Forty-eight records met study criteria and were
      reviewed. Our series' size and heterogeneity prevents drawing conclusions
      regarding treatment effectiveness. The majority (67.5 per cent) of our patients
      were treated by surgery followed by irradiation. Our overall survival rates
      compare favourably with the general statistics although it should be noted that
      longer follow-up in our first group of patients may alter our results.
      Extracapsular spread did not adversely affect survival in our small series of
      five cases. We discovered six primary sites within one year and three additional
      cases within four years. The primary site was included in the radiation fields in
      all instances of squamous cell tumours that were eventually found. It has been
      suggested than eventual manifestation of the primary site adversely affects
      prognosis, which is in agreement with our results.

PMID- 8733458
TI  - An audit of prophylactic antibiotic treatment following tonsillectomy in
      children.
AB  - A prospective audit study was undertaken to assess the effect of two different
      management policies following tonsillectomy in children in this hospital, one of
      which requires a prophylactic five-day course of oral antibiotics and the other
      doses not. A total of 95 children were entered into the trial: 54 received post
      operative antibiotics and 41 did not. The post-operative recovery was assessed by
      completion of a parent questionnaire which included the following parameters:
      degree of patient distress, nausea and vomiting, otalgia, halitosis, pharyngeal
      bleeding, analgesic requirement, day of return to a regular diet and General
      Practitioner consultation. There was no significant reduction in any of the
      morbidity measures in patients treated with antibiotics. I fact, the analgesic
      requirement and the incidence of otalgia and irritability on Days 6 and 7 and
      secondary haemorrhage were significantly higher in the antibiotic-treated
      patients. Although the number of patients included in this study are small, the
      result suggest that post-operative antibiotics do not improve the outcome of
      uncomplicated tonsillectomy. Our previous practice of routinely administering
      antibiotics to post-tonsillectomy children has been discontinued as the
      consequence of this audit.

PMID- 8733459
TI  - The 'Darling' elbow rest--an aid to a stable operating position in endoscopic
      sinus surgery.
AB  - The 'Darling' elbow rest provides a compact, easily manoeuvrable platform for the
      surgeon's elbow during endoscopic sinus surgery, stabilizing the endoscope and
      increasing operative safety.

PMID- 8733460
TI  - An improvement in hearing sensitivity following hearing-aid fitting in a child
      with an apparent sensorineural hearing impairment.
AB  - This case describes an apparent improvement in hearing sensitivity in a young
      girl over a period of 12 months, after she was fitted with binaural hearing-aids.
      Discrepancies between objective and subjective test results are highlighted. Even
      if the underlying reason for the conflicting test results was due to poor
      listening skills or test error, this child behaved like a hearing-impaired child
      and her performance improved after hearing-aid use. The case also illustrates the
      application of earphone testing from six months of age. The importance of closely
      monitoring all children who are fitted with hearing-aids is highlighted.

PMID- 8733461
TI  - Vestibular schwannoma and the only hearing ear.
AB  - With the recent advances in the management of vestibular schwannomas, it is
      possible not only to save the facial nerve function but also preserve hearing in
      a small percentage of cases. Difficulties arise while managing patients with
      vestibular schwannoma in their only hearing ear. In this article we summarize our
      experience in managing seven of these patients. We recommended a watch and wait
      policy with a regular follow-up with audiometric testing and gadolinium-enhanced
      magnetic resonance imaging (MRI). Gamma knife radiosurgery is advised in cases
      with deterioration of hearing or increase in tumour size. Surgery is usually
      avoided unless there are brainstem compression symptoms.

PMID- 8733462
TI  - Cerebellopontine angle metastasis from clear-cell renal carcinoma presenting as
      bleeding from the ear.
AB  - Metastatic lesions in the cerebellopontine angle are rare. We encountered one
      such metastatic lesion from clear-cell renal carcinoma that had a striking
      clinical appearance, bleeding from the ear and multiple lower cranial nerves'
      involvement. While the overall prognosis in CNS metastasis from systemic
      malignancy is gloomy, useful palliation can be achieved in patients with solitary
      lesions.

PMID- 8733463
TI  - The role of MIBG scintigraphy in the management of a case of metastatic glomus
      jugulare tumour.
AB  - Glomus jugulare tumours with metastases are rare as the diagnosis of metastases
      in this condition can be difficult. In the past this diagnosis has been made on
      histology of the metastatic lesions which were identified on clinical grounds.
      This is one of the reasons why there have been only 20 reported cases in the
      literature up to 1990 (Johnstone et al., 1990). This case report examines the
      role of meta-iodobenzylguanidine (MIBG) scintigraphy in the diagnosis of
      metastases. MIBG scintigraphy is an injected radionucleotide isotope scanning
      technique which is cheap, non-invasive, sensitive as well as being a specific
      investigation for identifying sites of ectopic neuroendocrine tissue. It may also
      have a role in the treatment of these tumours.

PMID- 8733464
TI  - Heterotopic pleomorphic adenoma of the external nose.
AB  - Pleomorphic adenomas arising from sites other than the major or minor salivary
      glands are uncommon. We describe a case of pleomorphic adenoma in the
      subcutaneous tissue of the nasomaxillary crease. An identical tumour was
      previously excised from the right nasal cavity. The possible aetiology of these
      heterotopic salivary gland tumours is discussed.

PMID- 8733465
TI  - Persistent nasal crusting due to hypohidrotic ectodermal dysplasia.
AB  - Hypohidrotic ectodermal dysplasia is an hereditary condition of the ectodermal
      tissues which may escape recognition because of lack of clinical awareness due to
      its rarity. Otorhinolaryngological features of this syndrome include chronic
      respiratory tract infections, persistent foul-smelling nasal discharge and crust
      formation, and hearing problems. The condition is usually an X-linked recessive
      disease affecting mainly ectodermal tissue, although nonectodermal tissue may
      also be affected. The notation 'ectodermal' is used because ectodermal tissues
      are always involved. The syndrome is characterized by complete or partial absence
      of sweat glands, sparse hair growth, absent or deformed peg teeth, sparse
      sebaceous glands, occasional absence of salivary and lacrimal glands, scanty
      mucous glands and deficient cilia. We describe two children with this disorder
      with specific reference to the effect on the upper respiratory tract.

PMID- 8733466
TI  - Vocal fold palsy after use of the laryngeal mask airway.
AB  - We report two cases of left vocal fold palsy following use of the laryngeal mask
      airway. In both cases anaesthesia was uneventful with a duration of about 60
      minutes. It is proposed that high intra-cuff pressures induced during anaesthesia
      resulted in distension of the hypopharynx and subsequent neuropraxia of the motor
      branches of the recurrent laryngeal nerve and the external branch of the superior
      laryngeal nerve.

PMID- 8733467
TI  - Bilateral ventricular neurofibroma of the larynx.
AB  - Laryngeal neurofibroma (LNF) is an unusual tumour and only approximately two
      dozen cases have been reported previously. Isolated LNF not associated with von
      Recklinghausen's disease is even more unusual. According to a review of the
      available literature, the case presented is the first bilateral one and the first
      originating from the ventricles. The tumour was removed completely by
      microlaryngoscopy without tracheostomy. The macroscopic and light macroscopic
      findings are presented and a review of the literature on neurogenic tumours in
      the larynx is presented.

PMID- 8733468
TI  - Anisakiasis of the tonsils.
AB  - A six-year-old Indian girl presenting with clinical features of chronic recurrent
      tonsillitis, had a tonsillectomy. Histopathology revealed a cross-section of an
      Anisakis worm in the tonsil. This report documents a new location in the human
      host for this rare parasite.

PMID- 8733469
TI  - Glossal abscess presenting as unilateral tongue swelling.
AB  - Glossal abscesses are extremely rare, only 29 cases having been described in the
      last 28 years. Clinical and ultrasound examination should establish the
      diagnosis, and treatment should be by surgical incision and drainage. We report a
      case of glossal abscess presenting as a unilateral swelling of the tongue.

PMID- 8733470
TI  - Fourth branchial arch fistula.
AB  - A case is presented of a rare congenital anomaly of the fourth branchial arch,
      which presented as an abscess in the anterior triangle, related to a fistula
      communicating with the pyriform fossa. Histopathological examination showed the
      fistula to be associated with thyroid tissue supporting the hypothesis that the
      ventral wing of the fourth pouch contributes to the thyroid gland.

PMID- 8733471
TI  - Trigeminal neuralgia in nasopharyngeal carcinoma.
AB  - Tumours at the skull base may show perineural infiltration of the mandibular
      nerve. Subsequent retrograde spread into the cavernous sinus, Gasserian ganglion,
      the trigeminal nerve and the pons may be seen. The patient, a known and treated
      case of nasopharyngeal carcinoma (NPC), complained of trigeminal neuralgia and
      difficulty in chewing. Magnetic resonance imaging (MRI) revealed a Gasserian
      ganglion and trigeminal infiltration with resultant atrophy of the muscles
      innervated by the mandibular nerve. Proximal cranial nerve involvement should be
      suspected in patients with skull base malignancy presenting with trigeminal
      neuralgia. MRI is the modality of choice in delineating the pathological process.

PMID- 8733472
TI  - Epithelial-myoepithelial carcinoma--report of a case arising in the nasal cavity.
AB  - We present an extremely rare case of epithelial-myoepithelial carcinoma (EMC)
      arising in the nasal cavity. The patient was a 56-year-old Japanese male with a
      polypoid tumour arising from the nasal septum. Histopathological examination
      revealed the tumour to consist of a solid proliferation of clear-cells and, in
      some areas, small or elongated duct structures with a double-layered arrangement
      of inner cuboidal cells and outer clear-cells. Dual differentiation toward
      myoepithelial and ductal cells were confirmed immunohistochemically. The
      occurrence of EMC in the nasal cavity is possible and this entity should be
      generally recognized by surgical pathologists, not only those engaged in head and
      neck surgery.

PMID- 8733473
TI  - Leiomyosarcoma of the parotid gland.
AB  - A 36-year-old patient with a primary leiomyosarcoma of the left parotid gland is
      presented. To our knowledge this is only the second case of a parotid
      leiomyosarcoma in the world according to the literature review.

PMID- 8733474
TI  - Dynamic analysis of the evolution of a novel genetic system: the evolution of
      ciliate meiosis.
AB  - Many ciliates undergo a peculiar form of meiosis in which four haploid nuclei are
      produced, three are digested, and the single remaining nucleus undergoes mitosis.
      It is paradoxical that such a meiotic process occurs, since one could imagine
      several other less costly ways of producing two nuclei. Here we investigate a
      possible resolution of this paradox. It is shown that the spread of a selfish
      gene that kills the mate not containing it, provides the conditions for the
      spread of a costly modifier of the form of meiosis. We investigate the conditions
      under which the modifier can fixate.

PMID- 8733475
TI  - Self-organization and competition in evolution: a conceptual problem in the use
      of fitness landscapes.
AB  - Recently it has been claimed that certain macroevolutionary patterns, such as the
      contrast between the Cambrian explosion and the Permian quiescence, can be
      explained as generic properties of selection processes, i.e. as features that are
      not caused by specific selection pressures, but that are to be expected in any
      selection process. The explanations are based on models of motions on randomly
      generated fitness landscapes, which are assumed to be representative of fitness
      landscapes in general. In this paper I show that such explanations of
      macroevolutionary patterns are conceptually flawed. If the concept of fitness
      used in the model is not the customary biological notion of fitness, there is no
      reason why organisms with higher fitness should displace organisms with lower
      fitness, and as a result the motion of a point representing a population is no
      longer determined by the shape of the fitness landscape. Nothing can be derived
      about the motions on the landscape, and the explanation collapses. If the model
      is based on the customary fitness concept, non-competing species have to be
      assigned the same fitnesses. As most species belonging to a radiation such as the
      Cambrian explosion are assumed to coexist, the majority of species will have the
      same fitness. A radiation of species can therefore not be modeled meaningfully on
      a fitness landscape.

PMID- 8733476
TI  - Tumour progression: random mutations or an integrated survival response to
      cellular stress conserved from unicellular organisms?
AB  - The current paradigm states that cancer progression is caused by random
      independent mutations, each selected for its survival advantages. The accelerated
      rates of phenotypic changes, the pleiotropic effect of several genes involved in
      progression--which need not be necessarily mutated for inducing the observed
      changes in cancer cell behaviour--lead us to propose an alternative hypothesis.
      Malignant progression might be a result of the unveiling of a cell-survival
      program, induced by various aggressions in the same way as the SOS system is
      induced and regulated in bacteria. This hypothesis depends on the homology
      between several genes involved in cancer progression (such as bcl2, mdm2, the
      mismatch repair genes, the heat shock protein genes, the pleiotropic resistance
      genes, the telomerase gene ...) and several genes involved in the survival of
      prokaryotes and eukaryotes under stress. The development of multicellular
      organisms could not take place without the building of a control program,
      exemplified by the so-called anti-oncogenes. However, this control program had to
      integrate some weaknesses, in order to allow for embryogenesis, growth, and wound
      healing. These weaknesses, neutral from an evolutionary point of view--since most
      cancers are sporadic and kill their hosts long after the birth of the offspring-
      are exploited by the survival program of individual cells, inherited from the
      genome of prokaryotes and unicellular eukaryotes, and repressed but not
      suppressed in animals. If this theory is true, it is probable that (i) no anti
      oncogenes will be found in unicellular organisms, (ii) the sensitivity to
      mutations will be higher in genes involved in proliferation and in anti-oncogenes
      such as p53 and Rb, than in genes not involved in the cancer process, (iii) a
      process of transfer of genetic information exists in cancer cells as it exists in
      bacteria. The identification of the genes governing the survival program could
      lead to new therapeutic approaches.

PMID- 8733477
TI  - Expansion of mutant stem cell populations in the human colon.
AB  - In general, it is presumed that colonic epithelial stem cells are the principal
      cell type at risk of incurring the series of somatic mutations leading to
      carcinoma, since all other epithelial cell types are short-lived. Mutant stem
      cell clonal expansion increases the risk for subsequent mutations and is
      therefore a potentially important step in carcinogenesis. The stem cells reside
      in colonic crypts, simple tubular foldings of the epithelium, and thus counting
      crypts provides an indirect means to determine stem cell numbers. The normal
      crypt population is known to expand through a process of crypt replication and
      this is thought to result in a corresponding expansion of the epithelial stem
      cell population. A simple mathematical model of the population dynamics of normal
      and mutant crypts (crypts containing mutant stem cells) is developed and used to
      estimate a lower bound on the relative rate of expansion of the mutant stem cell
      population. The model predicts that if mutant and normal crypt populations expand
      at the same rate, and if the mutation rate is small relative to the rate of
      growth, then the fraction of clusters of mutant crypts composed of only a single
      mutant crypt should steadily decrease with age towards one-half. Aberrant crypts
      are easily recognizable lesions in human colon which have frequently been shown
      to contain cells with K-ras and occasionally APC gene mutations. Application of
      the model to recent counts of aberrant crypt cluster sizes indicate that the
      aberrant crypt population, and the contained mutant stem cell population, is
      expanding substantially faster than normal.

PMID- 8733478
TI  - Different biological species "broadcast" their DNAs at different (G+C)%
      "wavelengths".
AB  - Radio can be used as a metaphor for the transmission of information by DNA
      through time and space. Just as different radio transmitters broadcast at
      different wavelengths to prevent interference, so different biological species
      "broadcast" their DNAs at different (G+C)% "wavelengths" to prevent
      recombination. It is postulated that species differences in (G+C)% prevent
      recombination. First, evidence is presented supporting the early Crick-Sobell
      stem-loop model for genetic recombination, which proposes that the rate-limiting
      step in recombination is the recognition ("kissing") of complementary sequences
      in the loops of stem-loop structures extruded from supercoiled DNA. Then, various
      ways in which differences in (G+C)% might impede complementary loop interactions
      are outlined. The strength of the postulate is that it brings together a variety
      of disparate observations in fields that have not previously been seen as
      related. Thus, explanations are apparent for why most mutations are not
      selectively neutral (the "neutralist/selectionist" debate), why introns were
      present in the earliest genes (the "introns-early/introns-late" debate), and the
      origin of species.

PMID- 8733479
TI  - On the role of synaptotagmin in synaptic vesicle exocytosis.

PMID- 8733480
TI  - The limit of PCR amplification.

PMID- 8733481
TI  - High dose rate endobronchial brachytherapy for the treatment of lung cancer:
      current status and indications.

PMID- 8733482
TI  - Oxidant/antioxidant imbalance in smokers and chronic obstructive pulmonary
      disease.

PMID- 8733483
TI  - Beta 2 adrenoceptor polymorphisms: are they clinically important?

PMID- 8733484
TI  - High dose rate brachytherapy for the local control of endobronchial carcinoma
      following external irradiation.
AB  - BACKGROUND: External irradiation is an established palliative treatment for
      patients with inoperable lung cancer. However, persistent or recurrent symptoms
      due to local disase are common following external irradiation. The impact of high
      dose rate (HDR) brachytherapy in the palliative management of patients with local
      sequelae of residual or recurrent endobronchial lung carcinoma following external
      irradiation was investigated. METHODS: A prospective cohort of 29 patients (19
      men, mean age 65 years) underwent HDR brachytherapy for inoperable lung cancer.
      All patients had completed external irradiation at least one month before entry
      into the study (mean (SD) dose 4400 (1481) cGy, completed 12.9 (21.3) months
      previously). Patients underwent outpatient bronchoscopic placement of 1-3 HDR
      brachytherapy catheters for delivery of 750-1000 cGy of intraluminal irradiation
      every two weeks on 1-3 occasions. Prospective evaluation before and four weeks
      after completion of HDR brachytherapy included assessment of indices of level of
      function, symptoms, extent of atelectasis (chest radiography), and bronchoscopic
      determination of degree of endobronchial obstruction. RESULTS: One hundred and
      eighteen catheters were placed in 81 treatments. Eleven of the 26 patients who
      underwent repeat bronchoscopy showed a reduction in the degree of endobronchial
      obstruction; five of 18 patients had radiographic improvement in the extent of
      atelectasis. Positive response rates ranged from 25% for signs and symptoms
      related to pneumonitis to 69% for haemoptysis. Performance status improved in 24%
      of patients. Two patients died before completion of the study protocol. Short
      term complications included one episode of non-fatal, massive haemoptysis, five
      of minor haemoptysis, and one pneumothorax. CONCLUSIONS: HDR brachytherapy may
      improve the degree of endobronchial obstruction, atelectasis, symptoms, and level
      of function with minimal short term complications in patients with recurrent or
      residual symptomatic disease following external irradiation.

PMID- 8733485
TI  - Anti-CEA immunoscintigraphy and computed tomographic scanning in the preoperative
      evaluation of mediastinal lymph nodes in lung cancer.
AB  - BACKGROUND: Thoracic computed tomography (CT) provides most of the staging
      information needed before operation for lung cancer and can reduce the number of
      exploratory thoracotomies. In recent years a new immunoscintigraphic technique
      with anti-carcinoembryonic antigen (CEA) monoclonal antibodies has been shown to
      be effective in lung cancer staging. This study compares the yields of CT scans
      and immunoscintigraphy in the preoperative evaluation of the medistinal lymph
      nodes of patients with non-small cell lung cancer. METHODS: One hundred and
      thirty one patients believed on clinical grounds to have a operable non-small
      cell lung cancer were photoscanned with the indium-111 labelled F(ab')2 fragments
      of the antibody FO23C5. Both planar and single photoemission computed tomography
      (SPECT) thoracic views were recorded. CT scan of the thorax, abdomen, and brain
      were obtained in all patients. Seventy of the patients eventually underwent
      surgery, an additional seven underwent mediastinoscopy or mediastinotomy, and a
      further 10 had both cervical exploration and thoracotomy. Pathological evaluation
      of the mediastinal nodes was available in all 87 patients, but in only 80 of them
      was the diagnosis of lung cancer eventually confirmed. RESULTS: The diagnostic
      accuracy of planar immunoscintigraphy, SPECT immunoscintigraphy, and CT scanning
      for N2 disease was 76%, 74%, and 71%, respectively. The corresponding sensitivity
      and specificity rates were 45%, 77%, 64% and 88%, 72%, and 74%. These were not
      significantly different. CONCLUSIONS: This study shows that anti-CEA
      immunoscintigraphy has no advantage over conventional CT scanning in assessing
      mediastinal lymphoadenopathy in patients with lung cancer. CT scanning remains
      the gold standard test in these patients.

PMID- 8733486
TI  - Nebulised antipseudomonal antibiotic therapy in cystic fibrosis: a meta-analysis
      of benefits and risks.
AB  - BACKGROUND: To establish the benefits and risks of nebulised antipseudomonal
      therapy in cystic fibrosis the results of relevant randomised controlled trials
      were combined. METHODS: The therapeutic end points compared were (a) number of
      pulmonary exacerbations requiring treatment with systemic antibiotics, (b)
      measurable alteration in respiratory tract pseudomonal load, (c) alteration in
      lung function on spirometric assessment, (d) development of resistance in
      respiratory tract Pseudomonas strains to the nebulised antipseudomonal used in
      each randomised controlled trial, and (e) renal and auditory impairment. RESULTS:
      Five studies were suitable for meta-analysis, eight others could not be included
      because of inadequate outcome description or the lack of appropriate
      randomisation. Meta-analysis shows benefit for nebulised antipseudomonal
      antibiotic therapy with no demonstrable adverse effect other than a possible
      increase in in vitro antibiotic resistance of Pseudomonas aeruginosa of the
      respiratory tract. CONCLUSIONS: Although inferences drawn from individual
      randomised controlled trials concerning the benefits and risks of this form of
      therapy are conflicting, pooled effect size establishes benefit with nebulised
      antipseudomonal antibiotic therapy and emphasises its relevance to the
      integration of information in other areas of controversy relating to the
      treatment of this disease.

PMID- 8733487
TI  - Minimisation of aminoglycoside toxicity in patients with cystic fibrosis.
AB  - BACKGROUND: There is evidence that administration of higher doses of
      aminoglycosides given less frequently improves the bactericidal effect and
      reduces the potential to cause side effects. To investigate this, a prospectively
      randomised open label therapeutic trial was undertaken in stratified groups of
      patients with cystic fibrosis to examine the efficacy and toxic potential of an
      aminoglycoside dosing regimen designed to generate high peak drug concentrations
      at 12 hourly intervals compared with conventional dosing at eight hourly
      intervals. METHODS: Patients in group A received tobramycin eight hourly using a
      dose aimed at generating a peak concentration of 10 mg/l with trough
      concentrations below 2 mg/l, and those in group B received the total daily dose
      required to achieve eight hourly target concentrations administered as two equal
      12 hourly doses. Clinical outcomes measured and assessed included vestibular
      symptoms, hearing and renal function, length of hospital stay, readmission rate,
      and mortality. RESULTS: Twenty nine patients were recruited during a six month
      period, 20 to group A and nine to group B. The average peak tobramycin level was
      higher in group B (12.5 (2.2) mg/l) than in group A (7.9 (1.9) mg/l), whilst the
      average trough level was higher in group A (0.8 (0.3) mg/l) than in group B (0.5
      (0.2) mg/l). There was a difference in the number of ototoxic events between
      patients in group A (seven of 18, 38.9%) and group B (none of eight), but no
      difference was found in other outcome measures assessed. CONCLUSIONS: These
      results suggest that 12 hourly high peak aminoglycoside dosing may be less toxic
      than equivalent eight hourly dosing, without any apparent difference in efficacy.

PMID- 8733488
TI  - Outcome for patients colonised with Burkholderia cepacia in a Birmingham adult
      cystic fibrosis clinic and the end of an epidemic.
AB  - BACKGROUND: There has been increasing concern since 1979 about the emergence of
      Pseudomonas cepacia (Burkholderia cepacia) in patients with cystic fibrosis in
      the UK and elsewhere. Colonisation of the sputum has been shown to be associated
      with increased morbidity and mortality. Evidence suggests person to person
      transmission and some centres have segregated those colonised with B cepacia from
      other patients with cystic fibrosis. The outcome of patients colonised by B
      cepacia has been studied, together with the effects of strict segregation.
      METHODS: The outcome in 18 patients with sputum colonised by B cepacia was
      compared with that in age, sex, and severity matched controls with no evidence of
      B cepacia colonisation by a retrospective case note study. RESULTS: No difference
      between cases or controls were found in the 24 month period prior to colonisation
      by B cepacia in lung function, number of days in hospital, or outpatient visits.
      Colonisation led to an increased rate of loss of lung function and utilisation of
      hospital services. There was an increase in the numbers of transplants and deaths
      amongst the cases. Since 1992 there have been only three new cases of B cepacia
      colonisation and the incidence and prevalence of the organism has fallen
      dramatically since segregation commenced. CONCLUSIONS: B cepacia appears to be
      linked to the decline in colonised individuals. There was no evidence that
      colonisation occurred in patients declining for other reasons. B cepacia
      colonisation confers a worse prognosis than Pseudomonas aeruginosa alone.
      Segregation appears to limit the spread of the organism from infected individuals
      to other patients with cystic fibrosis.

PMID- 8733489
TI  - Value of intracellular bacteria detection in the diagnosis of ventilator
      associated pneumonia.
AB  - BACKGROUND: Markers of ventilator associated pneumonia are of interest for
      confirming the diagnosis and for guiding the initial management of this frequent
      complication of mechanical ventilation. The detection of intracellular organisms
      in the polymorphonuclear leucocytes (PMNLs) and/or macrophages of bronchoalveolar
      lavage (BAL) fluid has been suggested as a specific test for the early indication
      of an infectious pulmonary process. METHODS: The diagnostic value of detecting
      intracellular organisms in two types of BAL fluid--protected (P-BAL) and
      conventional (C-BAL)--in 25 patients who died in one unit was prospectively
      studied. Immediately after death both P-BAL and C-BAL were performed bilaterally.
      Through a minithoracotomy on both sides of the chest bilateral bronchoscopically
      guided open lung biopsy samples were obtained from the same area, and an average
      of eight open lung blind biopsy samples (not bronchoscopically guided) were taken
      from each lung for histological examination. BAL fluid was examined for
      quantitative cultures (threshold 10(4) cfu/ml) and for the presence of
      intracellular organisms and extracellular organisms, and differential cell counts
      were also performed. RESULTS: Using the histopathology of the bronchoscopically
      guided open lung biopsies as the gold standard, detection of intracellular
      organisms in P-BAL (> or = 5%) and C-BAL (> or = 5%) fluids yielded 75% and 57%
      positive predictive values, and 83% negative predictive values, respectively.
      Prior treatment with antibiotics decreased the positive and negative predictive
      values of intracellular organism detection for both types of BAL fluid. The
      presence of intracellular organisms was correlated with the quantitative cultures
      of P-BAL and C-BAL samples. Quantitative cultures from P-BAL fluid were less
      sensitive (22% versus 45%) and more specific (100% versus 55%) than those from C
      BAL samples. The percentage of extracellular organisms and the differential cell
      count in P-BAL and C-BAL samples could not discriminate between the presence or
      absence of pneumonia. CONCLUSIONS: The presence of > or = 5% intracellular
      organisms infecting PMNLs or macrophages in P-BAL or C-BAL fluids is a specific
      marker of ventilator associated pneumonia.

PMID- 8733490
TI  - Community acquired pneumonia in adults: a study comparing clinical features and
      outcome in Africa (Republic of Guinea) and Europe (France).
AB  - BACKGROUND: Community acquired pneumonia is the most common cause of death from
      infectious disease both in western and developing countries. A study was carried
      out in Conakry, Republic of Guinea and Tours, France in order to compare signs,
      symptoms, severity of illness, risk factors, and clinical outcome of community
      acquired pneumonia in adult patients admitted to hospital. METHODS: The study was
      performed in the cities of Conakry and Tours over the same one year period.
      Patients with nosocomial pneumonia, tuberculosis, and those who were HIV positive
      were excluded. Data were recorded on the same forms in both centres. A severity
      score was calculated according to American Thoracic Society criteria. Follow up
      was evaluated at days 2, 7 and 15. RESULTS: A total of 333 patients (218 from
      Conakry, 115 from Tours) were included in the study with a diagnosis of community
      acquired pneumonia, with or without lung abscess or pleural effusion. Mean age
      was higher and pre-existing illness rate, dehydration, agitation, and stupor were
      more frequent in patients in Tours. Respiration rates of > 30 breaths/min and the
      incidence of crackles were identical in the two centres. Fever above 39 degrees
      C, initial shock, chest pain, and herpes were significantly more frequent in
      Conakry. Initial chest radiographic abnormalities were similar in the two groups,
      ranging from unilateral pleuropulmonary involvement (89% and 83% in Conakry and
      Tours, respectively) to diffuse patchy parenchymal disease. Parapneumonic
      effusion was present in 17% and 16% of the patients of Conakry and Tours,
      respectively. Pneumonia was considered to be severe in 33% and 42% of the
      patients, respectively. In Conakry first line antibiotic therapy was penicillin
      alone (2 million units a day) for 197 patients (90%) and second line antibiotic
      therapy was prescribed for 25 patients (12%). In Tours first line therapy
      consisted of a single antibiotic (amoxicillin, third generation cephalosporins)
      for 65 patients (57%) and second line antibiotic therapy was prescribed for 55
      patients (48%). The clinical outcome was similar in Conakry and Tours: 88% and
      85% of patients, respectively, were afebrile or clinically cured at day 15. The
      mortality rate was similar (6% and 8%, respectively). CONCLUSIONS: The problems
      encountered in the management of community acquired pneumonia are quite different
      in western and developing countries. This study shows that low doses of
      penicillin can cure 90% of African patients with pneumonia as effectively as more
      aggregative treatments in European patients who are both older and have greater
      comorbidity. Although pneumococci with reduced penicillin sensitivity occur in
      western countries, this does not seem to be the case in black Africa. For these
      reasons, low doses of penicillin or amoxicillin remain good first line treatment.

PMID- 8733491
TI  - Inhibition of the alveolar macrophage oxidative burst by a diffusible component
      from the surface of the spores of the fungus Aspergillus fumigatus.
AB  - BACKGROUND: Aspergillus fumigatus is a fungus that grows on dead and decaying
      organic matter in the environment and whose spores are present ubiquitously in
      the air. The fungus causes a range of diseases in the human lung. A study was
      undertaken to demonstrate and partially characterise an inhibitor of the
      macrophage respiratory burst from the surface of A fumigatus spores that could be
      an important factor in allowing the fungus to colonise the lung. METHODS: The
      spore-derived inhibitor of the respiratory burst of rat alveolar macrophages, as
      measured by generation of superoxide anion, was demonstrated in Hank's balanced
      salt solution extracts of four clinical isolates and an environmental isolate of
      A fumigatus. The time course of the release of the inhibitor into aqueous
      solution was assessed and the cytotoxic potential of the spore-derived inhibitor
      towards macrophages was tested using the propidium iodide method. An oxygen
      electrode was used to confirm the superoxide anion measurements. Molecular weight
      cutoff filters were used to determine the size of the inhibitor as assessed in
      the respiratory burst assay and also by its ability to inhibit macrophage
      spreading on glass. The crude diffusate from the spore surface was fractionated
      by reversed phase high pressure liquid chromatography (HPLC) and the fractions
      analysed for inhibitory activity, protein, and carbohydrate content. RESULTS: A
      small molecular weight (< 10 kD) heat stable toxin was released from the spores
      of clinical and environmental isolates of A fumigatus within minutes of
      deposition in aqueous solution. The key effect of the toxin demonstrated here was
      its ability to inhibit the oxidative burst of macrophages as measured by
      superoxide anion release. The inhibition was not due to cell death or detectable
      loss of membrane integrity as measured by permeability to propidium iodide. The
      toxin was not a scavenger of superoxide anion. Oxygen electrode studies suggested
      indirectly that the inhibitor acted to inhibit the assembly of the macrophage
      NADPH-oxidase complex. Fractions of < 10 kD also inhibited the spreading of
      alveolar macrophages, confirming that the toxin had an additional effect on
      macrophages that leads to loss of adherence or impairment of cytoskeletal
      function. In reversed phase HPLC fractions the inhibitory activity eluted with an
      associated carbohydrate, although the exact chemical nature of the toxin remains
      to be elucidated. CONCLUSIONS: This spore toxin may, through its ability to
      diffuse rapidly into lung lining fluid, diminish the macrophage respiratory burst
      and play a part in allowing A fumigatus to persist in the lung and manifest its
      well known pathogenic effects. Future research will be focused on further
      molecular characterisation of the toxin and elaboration of the effect of the
      toxin on intracellular signalling pathways involved in the activation of alveolar
      macrophages.

PMID- 8733492
TI  - High resolution computed tomographic findings in pulmonary tuberculosis.
AB  - BACKGROUND: Although chest radiographs usually provide adequate information for
      the diagnosis of active pulmonary tuberculosis, minimal exudative tuberculosis
      can be overlooked on standard chest radiographs. The aim of the present study was
      to assess the findings of active pulmonary tuberculosis on high resolution
      computed tomographic (HRCT) scans, and to evaluate their possible use in
      determining disease activity. METHODS: Thirty two patients with newly diagnosed
      active pulmonary tuberculosis and 34 patients with inactive pulmonary
      tuberculosis were examined. The diagnosis of active pulmonary tuberculosis was
      based on positive acid fast bacilli in sputum and bronchial washing smears or
      cultures and/or changes on serial radiographs obtained during treatment. RESULTS:
      With HRCT scanning centrilobular lesions (n = 29), "tree-in-bud" appearance (n =
      23), and macronodules 5-8 mm in diameter (n = 22) were most commonly seen in
      cases of active pulmonary tuberculosis. HRCT scans showed fibrotic lesions (n =
      34), distortion of bronchovascular structures (n = 32), emphysema (n = 28), and
      bronchiectasis (n = 24) in patients with inactive tuberculosis. CONCLUSIONS:
      Centrilobular densities in and around the small airways and "tree-in-bud"
      appearances were the most characteristic CT features of disease activity. HRCT
      scanning clearly differentiated old fibrotic lesions from new active lesions and
      demonstrated early bronchogenic spread. These findings may be of value in
      decisions on treatment.

PMID- 8733493
TI  - Potential effects of correction of inaccuracies of the mini-Wright peak
      expiratory flow meter on the use of an asthma self-management plan.
AB  - BACKGROUND: Patient self-management plans for asthma use peak expiratory flow
      (PEF) meter readings for decisions on adjusting asthma treatment. PEF meters have
      been shown to be inaccurate and the effect of this inaccuracy on such treatment
      plans has been determined. METHODS: PEF measurements were made by 127 severe
      asthmatic patients at least twice a day for at least two weeks using a mini
      Wright meter. The daily variation from "best" PEF and the within day PEF
      variability were calculated before and after correction for the meter's known
      inaccuracy. The effect of this data correction on the number of days when trigger
      points were reached for changing asthma therapy was then determined. RESULTS:
      Continuous PEF readings were available from 114 subjects with a median of 157.5
      days of data per subject (range 15-489 days). Correction of the PEF data led to
      the number of days of satisfactory asthma control being reduced in 72% of
      subjects with just one subject showing an increase in satisfactory control. Data
      correction reduced the percentage of total days of satisfactory control from 46%
      to 36% of days, and increased the days requiring more inhaled steroids from 33%
      to 36%. The days on which a course of oral corticosteroids was required increased
      from 16% to 23%. CONCLUSIONS: The accuracy of PEF meters significantly influences
      the interpretation of currently used asthma self-management plans. Managing
      asthma with the corrected PEF data would have increased the amount of treatment
      received by these patients since the severity of the asthma was underestimated by
      the raw data.

PMID- 8733494
TI  - Assessment of a new transtelephonic portable spirometer.
AB  - BACKGROUND: A new portable spirometer, the Spirophone, has been developed that
      records a subject's blow and can then transmit all the data by telephone to a
      receiving centre for analysis and comment. Tests of this device were undertaken
      to determine its accuracy and reliability. METHODS: The performance of the
      Spirophone was tested using computer generated wave forms, by delivering blows
      from calibrated syringes at different flows, and by comparing subjects' blows
      with those recorded with a commercial spirometer. RESULTS: Using computer
      generated wave forms all lung function indices were accurate to within 1% and
      blows delivered from calibrating syringes were accurate to within 5%. When
      subjects performed repeated forced vital capacity (FVC) manoeuvres there were no
      significant differences between lung function indices recorded with the
      Spirophone and with a commercial spirometer. With the Spirophone and commercial
      spirometer in series the FVC and forced expiratory volume in one second (FEV1)
      were within 5% of each other in nine out of 10 healthy subjects. CONCLUSION: The
      Spirophone recorded maximal forced expiratory manoeuvres with acceptable
      accuracy, reliability, and reproducibility, and this system offers the ability to
      monitor a patient's lung function at a centre remote from the patient.

PMID- 8733496
TI  - Difference between functional residual capacity and elastic equilibrium volume in
      patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: A study was performed to determine the elastic equilibrium volume
      (Vr) of the respiratory system in patients with chronic obstructive pulmonary
      disease (COPD). METHODS: Voluntary relaxed expiration from total lung capacity
      (TLC) was studied in three groups of subjects: seven patients with severe chronic
      airways obstruction (COPD), 10 normal subjects, and 15 subjects with restrictive
      disease. RESULTS: In the normal subjects and the patients with restrictive
      disease voluntary relaxed expiration from TLC stopped close to end tidal volume
      (FRC) and the volume expired in this manoeuvre was less than that expired in a
      slow vital capacity manoeuvre (SVC). In the patients with COPD the voluntary
      relaxed expiration continued beyond the end tidal volume (FRC) and the volume
      expired was not different from the SVC. Oesophageal (pleural) pressures and
      surface diaphragmatic EMG recordings in the patients with COPD supported the
      premise that relaxation was achieved. CONCLUSIONS: In patients with COPD, end
      tidal volume (FRC) is higher than the elastic equilibrium volume, Vr, of the
      respiratory system. This is in contrast to patients with restrictive disease and
      normal subjects in whom end tidal volume (FRC) is close to Vr. This study shows
      that, in patients with severe chronic obstructive pulmonary disease, Vr is at
      least as small as residual volume (RV).

PMID- 8733495
TI  - Acute asthma during pregnancy.
AB  - BACKGROUND: Acute asthma during pregnancy is potentially dangerous to the fetus.
      The aim of this study was to investigate the effect of an acute attack of asthma
      during pregnancy on the course of pregnancy or delivery, or the health of the
      newborn infant, and to identify undertreatment as a possible cause of the
      exacerbations. METHODS: Five hundred and four pregnant asthmatic subjects were
      prospectively followed and treated. The data on 47 patients with an attack of
      asthma during pregnancy were compared with those of 457 asthmatics with no
      recorded acute exacerbation and with 237 healthy parturients. RESULTS: Of 504
      asthmatics, 177 patients were not initially treated with inhaled corticosteroids.
      Of these, 17% had an acute attack compared with only 4% of the 257 patients who
      had been on inhaled anti-inflammatory treatment from the start of pregnancy.
      There were no differences between the groups as to length of gestation, length of
      the third stage of labour, or amount of haemorrhage after delivery. No
      differences were observed between pregnancies with and without an exacerbation
      with regard to relative birth weight, incidence of malformations, hypoglycaemia,
      or need for phototherapy for jaundice during the neonatal period. CONCLUSIONS:
      Patients with inadequate inhaled anti-inflammatory treatment during pregnancy run
      a higher risk of suffering an acute attack of asthma than those treated with an
      anti-inflammatory agent. However, if the acute attack of asthma is relatively
      mild and promptly treated, it does not have a serious effect on the pregnancy,
      delivery, or the health of the newborn infant.

PMID- 8733497
TI  - Transdiaphragmatic pressure in quadriplegic individuals ventilated by
      diaphragmatic pacemaker.
AB  - BACKGROUND: Electrophrenic pacing can be used in the management of ventilatory
      failure in quadriplegic patients. A study was undertaken to determine the pattern
      of transdiaphragmatic pressure (PDI) during the conditioning phase of
      electrophrenic pacing to see if it had a possible role in optimising the process
      of conditioning. METHODS: The tidal volume (TV) and PDI were measured in a group
      of six quadriplegic patients commencing ventilation by low frequency pulse
      stimulation (7-10 Hz) and low respiratory rate stimulation (< 10 breaths/min).
      RESULTS: Tidal volume increased between baseline and month 1 (4.33 ml/kg, p <
      0.001) and between months 1 and 2 (3.00 ml/kg, p < 0.05) and then stabilised. PDI
      was higher during bilateral diaphragmatic pacing (mean (SD) 1.73 (0.30) kPa) than
      with either left (1.15 (0.34) kPa) or right (0.86 (0.37) kPa) unilateral pacing.
      PDI varied throughout the observation period, probably by interaction between
      recovery of the diaphragmatic fibres and the pacing regimen. CONCLUSIONS:
      Patients with quadriplegia due to high spinal injury can be maintained with
      ventilation by continuous electrophrenic pacing. The control criteria used in
      this study for pacing were tidal volume and the patient's tolerance, and the PDI
      measurement did not contribute any additional information to help with managing
      the conditioning process.

PMID- 8733498
TI  - Pulmonary function in children with systemic lupus erythematosus.
AB  - BACKGROUND: Abnormalities of pulmonary function have been found in children with
      systemic lupus erythematosus (SLE) even in the absence of clinical or
      radiographic evidence of pulmonary involvement. It is unknown whether these
      abnormalities represent an early sign of progressive lung disease or whether they
      are associated with disease activity. METHODS: After a mean of 4.5 years,
      respiratory function (forced vital capacity (FVC) and single breath gas transfer
      factor (TLCO)) and disease activity were reexamined in 13 of 15 previously
      studied children with SLE. Disease activity was assessed by a validated index of
      SLE activity (SLE activity measure (SLAM)). RESULTS: In spite of the high
      prevalence of abnormalities of respiratory function at the baseline
      investigation, no chest radiographic abnormalities or overt clinical signs of
      lung disease were found at baseline, in the interval between the two
      investigations, or at the re-evaluation in any patient. From baseline to the
      second investigation the mean value of SLAM decreased and there was a trend
      toward an improvement in FVC and TLCO. TLCO was more severely impaired than FVC,
      being found as an isolated abnormality in a high percentage of patients (45% at
      baseline and 35% at follow up). There was a relationship between baseline TLCO
      and disease activity, expressed as a SLAM score. Moreover, there was a
      correlation between the changes in the SLAM score from baseline to the second
      investigation and the corresponding changes in the TLCO value, but not with the
      corresponding changes in the FVC value. CONCLUSIONS: In this series of patients
      the decrease in SLE activity from the first to the second investigation was
      associated with an improvement in pulmonary function. The presence of early
      isolated functional abnormalities was not associated with subsequent development
      of lung disease.

PMID- 8733499
TI  - Evaluation of nebulised acetylcysteine and normal saline in the treatment of
      sputum retention following thoracotomy.
AB  - BACKGROUND: The use of acetylcysteine as a mucolytic agent is controversial. In
      1962 it was claimed to be "the most effective agent ... for the liquefaction of
      ... secretions" but was subsequently taken off the market as a respirator
      solution. Normal saline, on the other hand, is becoming increasingly popular. A
      study was undertaken to determine which solution is more effective at clearing
      retained secretions following thoracotomy. METHODS: The study included 10
      patients and was of single blind, two-way crossover design. Measurements taken
      before and after each treatment included sputum viscosity, difficulty of
      expectoration, weight of sputum expectorated, and oxygen saturation. RESULTS:
      Following nebulisation of acetylcysteine, sputum viscosity was reduced,
      difficulty of expectoration was reduced, the weight of sputum expectorated was
      increased, and oxygen saturation was increased. There were no changes after
      nebulisation of normal saline. CONCLUSIONS: This study shows that, following
      thoracotomy, nebulised acetylcysteine reduces sputum viscosity, making
      expectoration easier and improving oxygenation. Nebulised normal saline has no
      effect.

PMID- 8733501
TI  - Occupational asthma: measures of frequency from four countries.
AB  - Disease registers and surveillance schemes are not necessarily designed to
      measure incidence and prevalence, but their data can provide useful
      epidemiological insights. Their main functions are the detection and
      identification of hazards so that further cases can be prevented, and to provide
      a database for research to improve our understanding of the determinants and
      consequences of disease. Occupational asthma probably accounts for only a small
      proportion of adult asthma, of the order of 2-6% in the UK. On the other hand,
      asthma is very common and so thousands of people in the UK and in other western
      countries have asthma as a result of their work. The frequency of the disease in
      less developed countries is unknown but is potentially very large. Information on
      incidence is patchy but from Finland, where ascertainment is most complete, there
      are approximately 140 per million working people affected each year, and even
      there disease in the self-employed is probably missed. Data for the UK are
      limited to cases seen by specialist physicians and the best estimate is that the
      annual incidence of such cases is about 50 per million. Through internal
      comparisons and analysis it is possible to judge the extent to which variation in
      ascertainment and reporting have affected the frequency of reported disease, but
      so far it has not been possible to measure the underestimation due to persons
      with work-related symptoms not seeking medical attention or not being referred to
      a specialist.

PMID- 8733500
TI  - Home assessment of peak inspiratory flow through the Turbohaler in asthmatic
      patients.
AB  - BACKGROUND: The efficacy of dry powder inhalers depends on the patient's
      inspiratory flow. Drug delivery from the Turbohaler (Turbuhaler in some
      countries), a multidose powder inhaler, is optimal at flows of > 40 l/min. The
      aim of this study was to investigate the peak inspiratory flow that can be
      generated by asthmatic patients through the budesonide Turbohaler (PIFTBH) during
      maintenance treatment at home. METHODS: Thirty asthmatic patients, consecutively
      recruited from the outpatient clinic, inhaled their maintenance dose of 800 (n =
      16) or 1600 micrograms/day (n = 14) for two months or one month, respectively.
      The Turbohaler was connected to a modified Vitalograph Compact installed at home
      to obtain printed PIFTBH values for all inhalations. Peak expiratory flow (PEF)
      was measured twice daily. RESULTS: Flows were remarkably constant with individual
      mean PIFTBH values ranging from 55 l/min to 95 l/min. Only 13 of the 5248 PIFTBH
      recordings taken at home (three patients) were < 40 l/min and all were > 30
      l/min. Weekly mean morning PEF values ranged from 114 l/min to 733 l/min. PIFTBH
      values could not be accurately predicted from lung function parameters in
      individual patients. CONCLUSIONS: In a group of stable asthmatic patients
      inspiratory flow rates rarely fell below the 40 l/min needed to operate a
      Turbohaler.

PMID- 8733502
TI  - In vivo veritas: the continuing importance of discoveries in complex biosystems.
AB  - The common belief that reductive biological sciences--for example, molecular
      biology and cellular chemistry--will write the book of revelation of all future
      anti-asthma drugs is at variance with the demonstrated importance of discoveries
      in complex in vivo systems.

PMID- 8733503
TI  - Co-existing conjunctival non-Hodgkin's lymphoma and pulmonary sarcoidosis.
AB  - A 55 year old woman with a conjunctival non-Hodgkin's lymphoma was found to have
      pulmonary nodules on a thoracic computed tomographic scan which were initially
      thought to be lymphomatous deposits. A subsequent biopsy specimen demonstrated
      granulomas consistent with sarcoidosis. The relationship between sarcoidosis and
      malignancy, in particular lymphoma, is discussed.

PMID- 8733504
TI  - Pneumocystis carinii in a patient with pulmonary sarcoidosis and idiopathic CD4+
      T lymphocytopenia.
AB  - A case of pulmonary sarcoidosis and idiopathic CD4+ T lymphocytopenia is
      reported. Pneumocystis carinii was detected in the bronchoalveolar lavage fluid
      of a young homosexual man who was asymptomatic without any evidence of congenital
      or acquired immunodeficiency but with a low CD4+ cell count. A clinical and
      histological diagnosis of pulmonary sarcoidosis was made. During follow up the
      patient had oral candidiasis and a CD4+ cell count persistently below
      300/microliters. This case is highly suggestive of concurrent pulmonary
      sarcoidosis and idiopathic CD4+ T lymphocytopenia.

PMID- 8733505
TI  - Transphrenic dissemination of actinomycosis.
AB  - Thoracic actinomycosis is an uncommon disease and often presents difficulty in
      diagnosis. Two cases are presented in which thoracic actinomycosis produced
      fistulae between the thoracic and abdominal cavities. Surgical drainage and high
      dose penicillin for at least 4-6 months was the treatment of choice.

PMID- 8733506
TI  - Adenoid cystic carcinoma of the left main bronchus mimicking MacLeod's syndrome.
AB  - A 15 year old girl who was labelled as having MacLeod's syndrome on the basis of
      a chest radiograph was subsequently, at the age of 23 years, found to have an
      adenoid cystic carcinoma obstructing the left main bronchus. This case emphasises
      the need to exclude a central lesion in cases of unilateral hyperlucent lung.

PMID- 8733507
TI  - Occupational asthma due to latex in a hospital administrative employee.
AB  - A case is described of occupational asthma caused by indirect exposure to
      airborne latex allergens in an administrative hospital employee who never used
      latex gloves.

PMID- 8733508
TI  - Effectiveness of four different inhalers in COPD.

PMID- 8733509
TI  - Screening for breast cancer: the end of the beginning?

PMID- 8733510
TI  - The pathogenesis of chronic pancreatitis.

PMID- 8733511
TI  - Effects of physical activity and age on mitochondrial function.
AB  - It has been proposed that ageing results from the accumulation of mitochondrial
      DNA mutations with age which interfere with respiratory chain ATP production.
      Insufficient ATP production impairs cell function, and tissue dysfunction ensues,
      leading to morbidity, decline and eventually death. Supporting this theory,
      mitochondrial DNA mutations accumulate with age and respiratory chain function
      declines dramatically in human skeletal muscle. However, the extent of decline in
      respiratory chain function is greater (50%) than anticipated from the low levels
      of mitochondrial DNA mutations (< 1%) observed in aged muscle. We hypothesized
      that an age-related reduction in physical activity could be an important factor
      in this decline and thus studied the influence of chronological age on muscle
      mitochondria in subjects matched for levels of physical activity. In this
      carefully selected group, there was little correlation between oxidative
      metabolism and age. However, several parameters of respiratory chain function did
      correlate with markers of physical activity (activity score and handgrip
      strength). Our results suggest that reduced physical activity is a major
      contribution to the decline in mitochondrial oxidations during ageing. Physical
      activity ameliorates and may even mask mitochondrial 'ageing' in muscle.

PMID- 8733513
TI  - Early surgery in infective endocarditis.
AB  - Optimal timing of surgical intervention in infective endocarditis is important in
      reducing mortality. We prospectively studied 126 consecutive episodes of
      infective endocarditis treated in one institution over 5 years, with special
      emphasis on long-term results and on the effects on outcome of surgical
      interventions. Twenty-six patients (21%) underwent acute surgery on median
      treatment day 14. Mortality during treatment was 8% for patients undergoing acute
      surgery vs. 11% for those not undergoing surgery, and the adjusted 5-year
      survival rate of acute surgically treated patients was 91%, compared with 69% for
      the medically treated patients. Using univariate analysis, excess mortality
      during 5 years follow-up was associated with new cardiac decompensation at entry
      (p < 0.01), age (p < 0.01), no acute surgery (p < 0.05) and mitral valve
      involvement (p < 0.05). Multivariate analysis showed new cardiac decompensation
      at entry to be an independent predictor of cardiac death at 5 years follow-up
      (relative risk 2.39; CI 1.05-5.45), while no surgery during active disease
      implied a relative risk of 3.45, though not statistically significant. Patients
      undergoing surgery very early (< or = 10 days of treatment) did not have a poorer
      outcome. Acute valve replacement, as compared with medical therapy only, might be
      important to increase both short-term and long-term survival in infective
      endocarditis.

PMID- 8733512
TI  - Autoantibodies against bactericidal/permeability-increasing protein in patients
      with cystic fibrosis.
AB  - Cystic fibrosis (CF), a genetic disorder, is characterized by chronic pulmonary
      infection/inflammation which leads to respiratory failure. The presence of anti
      neutrophil cytoplasmic autoantibodies (ANCA) has previously been observed in the
      sera of patients with CF. In view of the known relationship of ANCA with primary
      vasculitis and of their putative pathogenetic role in these disorders, we studied
      the presence, specificity and isotype of ANCA and their clinical associations in
      66 adult CF patients. None of the 66 CF samples had autoantibodies to the major
      ANCA antigens, proteinase 3 or myeloperoxidase. However, 60/66 (91%) CF samples
      contained IgG, and 55/66 (83%) IgA, autoantibodies to bactericidal/permeability
      increasing protein (BPI), a recently-characterized ANCA specificity. All the IgA
      anti-BPI-positive samples were also IgG anti-BPI-positive. The autoantibody
      specificity was confirmed by inhibition assay and immunoblotting of CF sera
      against a neutrophil granule preparation. Furthermore, in this cross-sectional
      study, anti-BPI levels were inversely correlated with the observed reductions in
      FEV1 and FVC (IgA anti-BPI & FEV1: r = -0.508, p < 0.0001), and both IgG and IgA
      anti-BPI levels were higher in CF patients with secondary vasculitis (n = 6) than
      in those without (p < 0.05). ANCA with specificity for BPI were present in the
      majority of CF sera in this study and autoimmune processes may be associated with
      the development of pulmonary injury in CF.

PMID- 8733514
TI  - The increase in hay fever: pollen, particulate matter and SO2 in ambient air.
AB  - To investigate whether the rise in allergic disease is explicable on the basis of
      an increase in the concentrations of allergen and urban air pollutants to which
      the population has been exposed, we compared the concentrations of grass pollen,
      sulphur dioxide and black smoke to which two samples of children with previously
      measured prevalences of hay fever had been exposed, in Cardiff, South Glamorgan.
      In these studies there had been a 59% increase in the prevalence of hay fever
      among 12 year old school children between 1973 and 1988. Exposures to grass
      pollen of the two populations had been no different, but the earlier sample, with
      the lower prevalence of hay fever, had been exposed to substantially higher
      concentrations of ambient particulate matter and sulphur dioxide. The rise in
      prevalence of hay fever, occurring without a rise in grass pollen concentrations,
      supports the hypothesis that the population has become more susceptible to
      airborne allergen. This increased susceptibility is unlikely to be a consequence
      of concomitant exposure to sulphur dioxide and particulate air pollution.

PMID- 8733515
TI  - The clinical course and management of thoracic empyema.
AB  - We report a prospective multi-centre study of the clinical course and hospital
      management of thoracic empyema in 119 patients (mean age 54.8). The commonest
      presenting symptom was malaise (75%), 55% were febrile; 31% were previously well
      with no predisposing condition. Initial treatments were antibiotics alone (5),
      needle aspirations (46), intercostal tube drainage (61), rib resection (3) and
      decortication (4). Overall, intercostal drainage was used in 77 patients (16
      failed aspirations), surgical rib resection in 24 (1 failed aspirations, 20
      failed drainage), and surgical decortication in 28 (6 failed aspirations, 17
      failed drainage). Only 4 patients received intrapleural fibrinolytic agents.
      Aspiration and drainage were likely to fail if the empyema was > 40% of the
      hemithorax. Median time from treatment start to discharge was: aspirations, 26
      days; drainage, 23 days; resection 11 days; decortication, 12 days. Overall 21
      patients died (12 with empyema as the major cause); two had been surgically
      treated. Mortality correlated with age, diabetes, heart failure, and low serum
      albumin at admission. Infecting organisms, identified in 109 patients (92%)
      included anaerobes (37), Str. melleri (36), and Str. pneumoniae (28). Six months
      after discharge, all but six survivors had regained their previous health.

PMID- 8733516
TI  - Hepatitis C virus infection in the elderly.
AB  - We studied hepatitis C virus (HCV)-related disease in older people because the
      treatment rationale for younger asymptomatic patients is based on the long-term
      prognosis of infection. Of the HCV-antibody-positive patients seen at Freeman
      Hospital 1990-1994, 25 were > 65 years old; 24 were Caucasian and one was Afro
      Caribbean. Median age at presentation was 67 years, and five were female. Nine
      were asymptomatic at presentation, six presented with varices, five with malaise,
      three with abdominal pain, one with pruritus and one with oedema. Risk factors
      identified were: transfusion (7), haemodialysis (1), health care worker (dentist)
      (1), and tattoos (2). There was no recognized risk factor for infection in 14,
      but five of these had done military service in areas of high HCV prevalence.
      Liver biopsy in 20 showed chronic hepatitis in two, cirrhosis in 12, and
      cirrhosis and hepatocellular carcinoma in six. Three additional patients also
      developed hepatocellular carcinoma. HCV genotyping was done in 19 and all were
      type 1 (1a, 4; 1b, 14; 1 untypable, 1). Eleven died, at median age 71 years
      (range 65-94 years), five of HCV liver-related deaths and two from HCV-associated
      non-hepatic disorders (non-Hodgkin's lymphoma and fibrosing alveolitis).

PMID- 8733517
TI  - Treating paracetamol overdose by charcoal haemoperfusion and long-hours high-flux
      dialysis.
AB  - After serious paracetamol overdose, charcoal haemoperfusion was used to remove
      paracetamol from the circulation, aiming to reduce the severity of subsequent
      hepatic damage. Daily long-hours high-flux dialysis was given to patients with
      grade III-IV hepatic encephalopathy, and also to those at risk of developing
      encephalopathy. We reviewed patients treated in this manner who had not received
      N-acetylcysteine within the first 15 h after overdose. From January 1983 to
      January 1993, 73 patients with serious paracetamol overdose were seen, of whom 51
      received charcoal haemoperfusion and/or high-flux dialysis. Patients who were
      admitted within the first 42 h after overdose and who received haemoperfusion
      and/or dialysis had significantly lower peak levels of prothrombin time,
      bilirubin and creatinine than those who were admitted after 42 h. Mortality was
      also lower amongst patients admitted before 42 h, at 2/18 (11%) vs. 15/33 (45%),
      p < 0.05.

PMID- 8733519
TI  - The state of hypnosis: evidence and applications.

PMID- 8733518
TI  - The effects of ageing on glycation and the interpretation of glycaemic control in
      Type 2 diabetes.
AB  - To investigate the discrepancy in the assessment of glycaemic control using
      glycated haemoglobin (HbA1C) and glycated proteins (fructosamine), the effect of
      age on these variables was measured in non-diabetic individuals. In 232 non
      diabetics, there was a linear relationship between HbA1C and age (r = 0.49, p <
      0.0001). Mean HbA1C rose from 3.82% to 4.44% between the ages of 20 and 70.
      Consequently, when Type 2 diabetic patient samples (n = 128, median age 63 years)
      were classified according to European guidelines into good or poor glycaemic
      control using both an age-matched (n = 101) and a younger (n = 108, median age 37
      years) non-diabetic reference population, fewer patients were in good control
      (14% vs. 25%) and more in poor control (73% vs. 53%) when the younger reference
      population was used (both p < 0.05). In a subgroup of 126 non-diabetic subjects,
      HbA1C rose with age (r = 0.48), but serum fructosamine and fasting glucose did
      not (r = 0.07, r = 0.009, respectively, p = NS). Age-associated differences in
      non-diabetic HbA1C values may affect the assessment of glycaemic control in
      diabetic patients. It may also partly explain discrepancies found when comparing
      fructosamine with HbA1C as a measure of glucose control. Age-related HbA1C
      reference intervals may therefore be required for the treatment of patients and
      the accurate auditing of clinic performance.

PMID- 8733520
TI  - The NHS and the new scientism.

PMID- 8733521
TI  - Imipramine and amitriptyline in hyperactive children.

PMID- 8733522
TI  - Are calcium antagonists safe in hypertension?

PMID- 8733523
TI  - Funding, franchising, and effective primary care.

PMID- 8733524
TI  - Sarcoidosis.
AB  - Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. The
      condition commonly affects young adults and frequently presents with bilateral
      hilar lymphadenopathy with or without pulmonary infiltration, ocular or cutaneous
      lesions. The clinical presentation can be extremely varied depending upon the
      organs affected. The diagnosis is firmly established when recognised clinical and
      radiographic findings are supported by histological evidence of discrete non
      necrotising epithelioid cell granulomata in one or more organs. Sarcoidosis is
      usually self-limiting with spontaneous resolution, although in a few patients
      there is a progressive downhill course, culminating in irreversible fibrosis and
      severe impairment of organ function.

PMID- 8733525
TI  - The modernisation of general practice in the UK: 1980 to 1995 and beyond. Part I.
AB  - The UK is unusual in providing universal free healthcare in which access to
      specialists is largely controlled by general practitioners with 24-hour
      responsibility, throughout the year, for a defined list of patients of all ages.
      It is generally considered that this gatekeeper function has contributed to the
      relatively low cost of the National Health Service, but major changes in the
      organisation and clinical role of general practitioners have occurred,
      culminating in a new contract that aims to re-orientate general practice towards
      health promotion, disease prevention and the management of chronic disease. The
      implications of these changes are discussed.

PMID- 8733526
TI  - Adrenal incidentaloma: subclinical Cushing's syndrome.
AB  - Adrenal incidentalomas present a significant differential diagnostic challenge.
      All patients with an incidentally discovered adrenal lesion should be carefully
      considered and re-evaluated to exclude extra-adrenal malignancy. Tumours with
      hypersecretory syndromes require excision, whilst those tumours more than 6 cm in
      size, particularly if they exhibit other features of malignancy on computed
      tomography (CT), magnetic resonance imaging (MRI) or scintigraphy, should also be
      excised. In all cases screening for phaeochromocytomas should be performed, and
      in the context of hypertension and spontaneous hypokalaemia, a primary
      aldosterone-secreting tumour requires exclusion. However, the natural history and
      treatment regimens for those individuals demonstrating 'subclinical Cushing's
      syndrome' is far from clear. Size, as determined by CT or MR scanning, does not
      in itself reliably distinguish benign from malignant disease. Scintigraphy may be
      a useful adjunct, with discordant patterns suggesting malignant disease. Fine
      needle aspiration should not routinely be used but may be useful in cases of
      doubt about other extra adrenal malignancy.

PMID- 8733527
TI  - The specialist nurse in HIV/AIDS medicine.
AB  - The management of patients with human immunodeficiency virus infection requires a
      multidisciplinary holistic approach. Hospital-based specialist nurses can both co
      ordinate and facilitate their hospital care, and also ensure early and effective
      discharge back into the community.

PMID- 8733528
TI  - The development of healthcare services for diabetic prisoners.
AB  - The conditions experienced by people in custody in the UK have received
      considerable attention recently and there has been considerable debate concerning
      the standards of healthcare in British prisons. The Prison Health Care Service
      works under great pressure and difficulties and doctors have to deal with a large
      and ever-changing population, often with mental and physical disorders, who are
      frequently manipulative. This article highlights problems encountered in
      delivering diabetes care in prisons. Prisoners may self-induce diabetic
      ketoacidosis by refusing insulin injections, in order to be transferred to an
      outside hospital. On the other hand, prison staff may mis-interpret the symptoms
      of poorly controlled diabetes as 'acting up' by prisoners and inappropriate
      treatment can be given. If structured diabetes care is provided in prison,
      however, with close liaison between the Prison Staff and the local Diabetes Care
      Team, the basics of modern diabetes management can be provided. Good diabetic
      metabolic control can be achieved in the majority of patients, probably due to
      the rigid dietary regime, no alcohol and compliance with treatment. Imprisonment
      can ensure screening for diabetic complications and reassessment of treatment
      regimens. The British Diabetic Association guidelines for the provision of
      diabetes care in British prisons are outlined in this article.

PMID- 8733529
TI  - Satellite-delivered continuing medical education in Europe.
AB  - There is increasing recognition of the need for continuing medical education in
      the medical profession. There are now many ways of delivering medical education
      including conferences, books, journals amongst others. This paper describes a
      novel method of delivering medical education using satellite transmission. This
      medium allows live medical education programmes to be broadcast to over 150
      receiver sites in Europe. It also enables two-way live satellite links to be made
      between countries during the broadcast. EuroTransMed has an editorial board, in
      much the same way as a journal, which is representative of the differing medical
      societies in Europe. As the barriers between the various countries fall,
      EuroTransMed is an ideal medium to promote high quality, easily accessible,
      continuing medical education at a pan-European level.

PMID- 8733530
TI  - Reflux oesophagitis and Helicobacter pylori infection in elderly patients.
AB  - Helicobacter pylori is associated with gastritis, peptic ulcers and gastric
      malignancies. Little attention has been paid to the possibility that it may also
      have a role in the pathogenesis of reflux oesophagitis. This is especially true
      in elderly patients who have life-long infection and provide an ideal group to
      study the mucosal changes associated with the organism. The aim of this study was
      to determine if H pylori is associated with reflux oesophagitis in elderly
      patients. Consecutive gastroscopy patients were recruited. Multiple biopsies were
      taken from oesophagus, stomach, antrum and duodenum for histology and rapid
      urease tests. Patients also had IgG ELISA antibodies and 13C-urea breath tests
      performed. Patients with macroscopic or microscopic evidence of reflux
      oesophagitis were compared to patients with macroscopically normal upper
      gastrointestinal tracts and no microscopic evidence of reflux. A total of 114
      patients were recruited, average age 78.9 years (+/- 5.4). There were 37
      refluxers and 33 non-refluxers. We found no evidence for an association between
      the presence of H pylori and reflux oesophagitis in elderly patients. The high
      prevalence of H pylori in patients with reflux oesophagitis can be explained by
      the presence of incidental gastritis.

PMID- 8733531
TI  - Clinician beliefs underlying autopsy requests.
AB  - The aim of the study was to use psychological theory to identify and evaluate
      factors influencing clinical autopsy requests. A series of pilot interviews were
      conducted with 20 clinicians to identify beliefs about the benefits and
      drawbacks, social groups and circumstances influential in the decision to make an
      autopsy request. The most common beliefs, together with measures of intention to
      request autopsies, were incorporated into a questionnaire which was distributed
      among all appropriate clinicians in four hospitals. Statistical analyses
      identified which beliefs had the most influence on clinicians' intentions to
      request autopsies. A total of 145 clinicians returned the questionnaire, a
      response rate of 42%. Clinicians were significantly more likely to request
      autopsy the more they thought that the outcome of requesting would be of
      educational value, would confirm clinical diagnoses, would not distress
      relatives, would not be time-consuming and that the request itself would receive
      support from their consultant. An autopsy request was unlikely in circumstances
      where clinicians felt uncomfortable when requesting relatives' permission and
      when the patients were elderly. The fear of causing distress to relatives and the
      degree of support from the clinician's consultant were found to be the strongest
      predictors of intention to request autopsies. These are two areas in which
      intervention could help to increase autopsy request rates.

PMID- 8733532
TI  - Minoxidil, hypercoagulability and thromboembolic disease of the lung.
AB  - Minoxidil is a potent antihypertensive agent used in the treatment of resistant
      hypertension. A case is presented which illustrates a probably fatal interaction
      between minoxidil and a coagulation disorder.

PMID- 8733533
TI  - Nesidioblastosis-associated hypoglycaemia presenting with prominent cardiac
      manifestations.
AB  - We present a case of nesidioblastosis presenting with hyperinsulinaemic
      hypoglycaemia and electrocardiographic abnormalities.

PMID- 8733534
TI  - Acute airway obstruction by laryngeal haematomas in acute immune thrombocytopenic
      purpura.
AB  - We report the case of a 79-year-old woman with acute immune thrombocytopenic
      purpura who spontaneously developed laryngeal haematomas which produced acute
      upper airway obstruction.

PMID- 8733535
TI  - Caval umbrella causing obstructive uropathy.
AB  - A 49-year-old woman had a vena caval filters inserted having suffered multiple
      pulmonary emboli and a large upper gastrointestinal bleed. She re-presented five
      years later with loin pain and obstructive uropathy. She was found to have a
      right pelvi-ureteric obstruction due to inferior vena caval wall perforation from
      the vena caval filter.

PMID- 8733536
TI  - Acute pancreatitis due to zinc phosphide ingestion.
AB  - The case of a young woman is described who suffered from acute pancreatitis
      related to the ingestion of zinc phosphide. This unusual complication was
      successfully managed with conservative treatment.

PMID- 8733538
TI  - Adult respiratory distress syndrome due to mycoplasma pneumonia.
AB  - A previously fit 48-year-old man was admitted with an acute respiratory failure
      due to mycoplasma pneumonia that was confirmed by raised mycoplasma titre on
      complement fixation test. It was also associated with disseminated intravascular
      coagulopathy. The patient made a full recovery but required intermittent positive
      pressure ventilation.

PMID- 8733537
TI  - The tight pants syndrome--a sporting variant.
AB  - Tight neoprene 'warm pants' are increasingly utilised by sportsmen to prevent
      muscular injury. However, they may impede venous flow from the legs. We describe
      a case of extensive proximal deep vein thrombosis with subsequent pulmonary
      embolism in a fit young man with previous hip trauma.

PMID- 8733539
TI  - Thoracic spondylosis presenting with spastic paraparesis.
AB  - Spondylotic change of the spine is common in the cervical and lumbar regions and
      may present with compression of the spinal cord and nerve roots. Myelopathy due
      to degenerative disease in the thoracic spine is exceptional. Only a few cases
      have been reported in the literature and these reports have described disease in
      the lower four thoracic segments. We report a case of paraparesis caused by
      degenerative disease in the upper thoracic spine which has not previously been
      described.

PMID- 8733540
TI  - Stroke in a 24-year-old man.

PMID- 8733541
TI  - Congestive cardiac failure in a 65-year-old man.

PMID- 8733542
TI  - Cortical blindness in a 35-year-old man.

PMID- 8733543
TI  - The post-traumatic painful testis.

PMID- 8733544
TI  - Abdominal pain and vomiting in a paint stripper.

PMID- 8733545
TI  - Construction and application of hierarchical decision tree for classification of
      ultrasonographic prostate images.
AB  - A non-parametric algorithm is described for the construction of a binary decision
      tree classifier. This tree is used to correlate textural features, computed from
      ultrasonographic prostate images, with the histopathology of the imaged tissue.
      The algorithm consists of two parts; growing and pruning. In the growing phase an
      optimal tree is grown, based on the concept of mutual information. After growing,
      the tree is pruned by an alternating interaction of two data sets. Moreover, the
      structure and performance of the constructed tree are compared to the results
      using a slightly modified corresponding growing and pruning algorithm. The
      modified algorithm provides better retrospective and prospective classification
      results than the original algorithm. The use of the tree for automated cancer
      detection in ultrasonographic prostate images results in retrospective and
      prospective accuracy of 77.9% and 72.3%, respectively. Using this tissue
      characterisation, a supporting tool is provided for the interpretation of
      transrectal ultrasonographic images.

PMID- 8733546
TI  - Comparison between electrocardiographic and magnetocardiographic inverse
      solutions using the boundary element method.
AB  - The accuracy of imaging cardiac sources using electrocardiographic and
      magnetocardiographic signals is influenced by thoracic inhomogeneities, e.g. the
      lungs and cardiac blood masses. The effects is investigated of such
      inhomogeneities on the body-surface potential maps (BSPM) and magnetic-field maps
      (MFM) inverse solutions for a single moving dipole as the source model and a
      realistic torso model as the volume conductor, by employing a node-based boundary
      element method. Using the same number and placement of the body-surface potential
      and magnetic field leads, a comparison is obtained of the numerical accuracy of
      body-surface potential and magnetic field leads. The results show that, with no
      noise added, the body-surface potential solution is less sensitive to the
      exclusion of the inhomogeneities than the magnetic field solution. The influence
      of noise on the BSPM and MFM localization is comparable for x (left-right) and y
      (foot-head) oriented dipoles, and the BSPM localisation is more accurate than the
      MFM localisation for z (anterior-posterior) oriented dipoles.

PMID- 8733547
TI  - Uterine EMG spectral analysis and relationship to mechanical activity in pregnant
      monkeys.
AB  - The objective is to analyse internal and external recordings of uterine EMG in
      order to reveal common features and to assess the relationship between electrical
      activity and intra-uterine pressure modification. Three monkeys participated in
      the study, one as a reference and the others for data. EMGs are recorded
      simultaneously, internally by unipolar wire electrodes and externally by bipolar
      Ag/AgCl electrodes. Intra-uterine pressure is recorded as a mechanical index.
      Except for delay measurements, parameters are derived from spectral analysis and
      relationships between recordings are assessed by studying the coherence. Spectral
      analysis exhibits two basic activities in the analysed frequency band, and
      frequency limits are defined as relevant parameters for electrical activity
      description. Parameter values do not depend on the internal electrode location.
      Internal and external EMGs present a similar spectral shape, despite differences
      in electrode configuration and tissue filtering. It is deduced that external
      uterine EMG is a good image of the genuine uterine electrical activity. To some
      extent, it can be related to an average cellular electrical activity.

PMID- 8733548
TI  - Parametric modelling for electrical impedance spectroscopy system.
AB  - Three parametric modelling approaches based on the Cole-Cole model are
      introduced. Comparison between modelling only the real part and modelling both
      the real and imaginary parts is carried out by simulations, in which random and
      systematic noise are considered, respectively. The results of modelling the in
      vitro data collected from sheep are given to reach the conclusions.

PMID- 8733549
TI  - Discrimination between artefacts and contractions in pressure signals from the
      gastrointestinal tract by pattern recognition method.
AB  - A pattern recognition algorithm has been developed to discriminate between
      artefacts and contractions in interdigestive motility recorded by a pressure
      catheter with four channels from the human duodenum. A learning and a test set,
      both containing natural and induced artefacts, such as respiration and body
      movement, are obtained from five volunteers. The event classes were phase I, II
      and III contractions of the interdigestive motility complex and artefacts from
      respiration, cough, calibration signals and movements. Length, area, amplitude,
      inter-event interval, up- and downstroke, and correlation to other pressure
      channels and to respiration, are applied to classify the events. The sensitivity
      of the computer scoring increases with the number of applied features. When all
      the features are applied, the sensitivity of the Bayes' classifier against the
      visually scored contractions and artefacts is 0.96 with a specificity of 0.69.

PMID- 8733550
TI  - Effects of sino-aortic denervation on spectral characteristics of blood pressure
      and pulse interval variability: a wide-band approach.
AB  - Sino-aortic denervation (SAD) is employed in cats to evaluate the baroreflex
      influence on blood pressure (BP) and pulse interval (PI) spectral components from
      0.00008 to 0.9 Hz as assessed by FFT wide-band spectra and their 1/f modelling;
      and the linear coupling between BP and PI and between systolic and diastolic BP
      as assessed by coherence analysis. Specific procedures have been developed to
      obtain an effective smoothing of spectra and coherence functions. SAD induced an
      increase in BP powers from 0.03 to 0.0006 Hz and a power reduction of most of the
      remaining BP components; a reduction of PI powers at all frequencies; marked
      deviations of BP spectra from the 1/f trend; a reduction of the coherence between
      BP and PI from 0.12 to 0.5 Hz and a coherence enhancement at lower frequencies.
      These findings indicate that the arterial baroreflex modulates both fast and slow
      spectral components of BP and PI; homogeneously enhances PI fluctuations at all
      frequencies; produces differentiated effects on BP fluctuations along the
      frequency axis; and at low frequencies exerts the buffering action on BP through
      strategies which reduce the BP-PI linear link.

PMID- 8733551
TI  - Application of time series spectral analysis theory: analysis of cardiovascular
      variability signals.
AB  - The paper focuses on the most important application problems commonly encountered
      in spectral analysis of short-term (less than 10 min) recordings of
      cardiovascular variability signals (CVSs), critically analysing the different
      approaches to these problems presented in the literature and suggesting practical
      solutions based on sound theoretical and empirical considerations. The Blackman
      Tukey (BT) and Burg methods have been selected as the most representative of
      classical and AR spectral estimators, respectively. For realistic simulations,
      'synthetic' CVSs are generated as AR processes whose parameters are estimated on
      corresponding time series of normal, post-myocardial infarction and congestive
      heart failure subjects. The problem of resolution of spectral estimates is
      addressed, and an empirical method is proposed for model order selection in AR
      estimation. The issue of the understandability and interpretability of spectral
      shapes is discussed. The problem of non-stationarity and removing trends is dealt
      with. The important issue of identification and estimation of spectral components
      is discussed, and the main advantages and drawbacks of spectral decomposition
      algorithms are critically evaluated.

PMID- 8733552
TI  - Measurement of upper extremity orientation by video stereometry system.
AB  - In the attempt to gain a broader understanding of the causal relationships behind
      work-related symptoms of pain in the human shoulder, monitoring of arm position
      is crucial. Different methods have been used with varying accuracy. A video-based
      stereometry system, using infra-red light and reflecting markers for motion
      analysis, has been introduced for measurements in the fields of ergonomics,
      biomechanics and sports medicine. The purpose of this study is to investigate the
      sources of error in using this system for posture registration of the upper limb.
      Measurements are performed on a calibration fixture, on a mechanical model of the
      upper limb and on a subject with an exoskeleton. Particular, attention is given
      to inconsistencies and relative errors due to the finite geometrical precision
      with which the markers are positioned in the calibration fixture and on the
      studied objects, the limited capability to align the objects relative to the
      coordinate system of the calibration fixture and the errors connected to angular
      measurements using protractors etc. It is concluded that the system makes a
      valuable addition to existing instruments for non-contact posture measurement,
      and produces position data with an adequate accuracy in normal handling.

PMID- 8733553
TI  - Effect of pressure on transmural fluid flow in different de-endothelialised
      arteries.
AB  - The effect of pressure on filtration across different de-endothelialised arteries
      has been studied experimentally, and the existing theoretical model is validated.
      Segments of different arteries are excised, de-endothelialised and cannulated.
      Bovine serum albumin Krebs solution is used as perfusate. Transmural water flux
      is measured by following the movement of an air bubble in a calibrated capillary,
      which connects the artery to a pressure reservoir; the pressure of which is
      varied. The hydraulic conductivity Lp is calculated from the flux values. Using
      available experimental parameters in the case of the thoracic and abdominal
      aorta, a theoretical model is validated using the experimental results. As the
      elastic constant for the carotid artery is not available, the theoretical model
      is used to calculate the elastic constant at different transmural pressures. The
      values calculated are in the range -4.9 x 10(-8) to -5.7 x 10(-9) cm2 dyne-1
      between 50 and 135 mm Hg. Both theoretical and experimental results show a
      decrease in Lp values with an increase in transmural pressure for the thoracic
      and abdominal aorta, whereas a different trend is observed in the case of the
      carotid artery. The Lp values increase at 90 mm Hg, as compared with 50 mm Hg,
      and with a further increase in transmural pressure the values decrease.

PMID- 8733554
TI  - Computer-aided interpretation of pulmonary parameters in newborn infants.

PMID- 8733555
TI  - Modelling of myocardial temperature distribution during radio-frequency ablation.

PMID- 8733556
TI  - Parametric modelling of ECG signal.

PMID- 8733557
TI  - Cepstrum analysis of reflected pressure waves in stenosed arteries.

PMID- 8733558
TI  - Digital image analysis as a means of determination of urodynamic parameters.

PMID- 8733559
TI  - Infants' sensitivity to word boundaries in fluent speech.
AB  - Infants' sensitivity to word units in fluent speech was examined by inserting I
      sec pauses either at boundaries between successive words (Coincident versions) or
      between syllables within words (Noncoincident versions). In Experiment 1, 24 11
      month-olds listened significantly longer to the Coincident versions. In
      Experiment 2, 24 four-and-a-half- and 24 nine-month-olds did not exhibit the
      preference for the Coincident versions that the 11-month-olds showed. When the
      stimuli were low-pass filtered in Experiment 3, 24 11-month-olds showed no
      preference for the Coincident versions, suggesting they rely on more than
      prosodic cues. New stimulus materials in Experiment 4 indicated that responses by
      24 11-month-olds to the Coincident and Noncoindent versions did not depend solely
      on prior familiarity with the targets. Two groups of 30 11-month-olds tested in
      Experiment 5 were as sensitive to groups of 30 11-month-olds tested in Experiment
      5 were as sensitive to boundaries for Strong/Weak words as for Weak/Strong words.
      Taken together, the results suggest that, by 11 months, infants are sensitive to
      word boundaries in fluent speech, and that this sensitivity depends on more than
      just prosodic information or prior knowledge of the words.

PMID- 8733560
TI  - Consonant clusters in child phonology and the directionality of syllable
      structure assignment.
AB  - The production of target consonant clusters at early stages of acquisition is
      analysed from a phonological representational perspective. The data stem from
      five normal monolingual German and four normal monolingual Spanish children at
      ages from 0;9 to 2;1, observed in naturalistic settings. At the beginning stages,
      target clusters are reduced to a single consonantal position, due to lack of
      branching of the syllabic constituents. This finding coincides with other results
      in the literature, which have in general been explained by means of universal
      principles. Nevertheless, there is an essential difference between the German and
      the Spanish data: German children tend to prefer the first consonant and Spanish
      children the second one. This difference can only be explained in terms of
      parameterization of syllabification, which in German takes place from left to
      right and in Spanish from right to left. At later stages, when clusters begin to
      be produced with two consonantal positions, they offer evidence for the beginning
      of branching of syllabic constituents, due to parameterization, and for the
      chronological order of the setting of the subsyllabic parameters. Our data offer
      evidence in favour of the following acquisitional hierarchy: CV > CVC > CVCC >
      CCVCC.

PMID- 8733561
TI  - Context-sensitive underspecification and the acquisition of phonemic contrasts.
AB  - Several competing proposals for the (under)specification of phonological
      representations are evaluated against the facts of phonemic acquisition.
      Longitudinal evidence relating to the emergence of a voice contrast in the well
      documented study of Amahl (from age 2;2 to 3;11) is reconsidered. Neither
      contrastive specification nor context-free radical underspecification is capable
      of accounting for the facts. The problem is in the characterization of the change
      in the status of a feature from being noncontrastive and conditioned by context
      at one stage to being contrastive with phonetic effects that diffuse gradually
      through the lexicon. Both frameworks must treat as accidental the persistence of
      the early substitution pattern and require the postulation of wholesale changes
      in underlying representations, where these changes do not accord well with the
      observed phonetic changes or with the facts available to the learner. Context
      sensitive radical underspecification provides a plausible account of each stage
      and the transition between stages with minimal grammar change.

PMID- 8733562
TI  - An experimental test of phonemic cyclicity.
AB  - Laryngeal-supralaryngeal cyclicity has been put forth as an acquisition principle
      that describes expansion of the phonemic inventory as a bivalent cycle with
      alternations between the elaboration of laryngeal and supralaryngeal properties
      of the system (Gierut, 1994). This study evaluated experimentally the claims of
      the principle by manipulating the domain of the cycle and the phase relationship
      of the cycle as independent variables, and by monitoring longitudinally the order
      of emergent phonemic distinctions in the sound systems of seven children with
      phonological delays (aged 3;4 to 5;8) as the dependent variable. Three general
      findings emerged: (1) the course of acquisition for all children was consistent
      with cyclicity; (2) there were no differences in phonemic acquisition between
      children taught a laryngeal as opposed to a supralaryngeal distinction; and (3)
      children taught out-of-phase with the cycle evidenced greater phonemic expansion
      than those taught in-phase with the cycle.

PMID- 8733563
TI  - The development of syntactic subjects in Portuguese-speaking children.
AB  - In order to separate competence and performance factors in acquisition of
      knowledge of syntactic subjects, we audiotaped and analysed the spontaneous
      speech of 20 Portuguese-speaking two-year-olds in natural conversation with
      Portuguese-speaking adults. We separated the children into three groups based on
      Mean Length of Utterance in Words: 1.5-1.99; 2.0-2.99; 3.0-4.99. Our cross
      sectional data demonstrated that Portuguese-speaking children increased their use
      of subjects from 28% in the lowest-MLUW group to 57% in the highest-MLUW group.
      The children in the highest-MLUW group almost perfectly matched the adult
      speakers in the study on every measure. The increase in children's use of
      subjects was primarily due to an increase in the use of pronominal subjects. A
      comparison between Portuguese- and English-speaking children suggests that adult
      competence about the status of subjects is present at the onset of combinatorial
      speech, as shown by differential production of subjects. Each group also
      experiences performance limitations, as shown by the increase in subject use as
      development proceeds.

PMID- 8733564
TI  - Early passive acquisition in Inuktitut.
AB  - Passive structures are typically assumed to be one of the later acquired
      constructions in child language. English-speaking children have been shown to
      produce and comprehend their first simple passive structures productively by
      about age four and to master more complex structures by about age nine. Recent
      crosslinguistic data have shown that this pattern may not hold across languages
      of varying structures. This paper presents data from four Inuit children aged 2;0
      to 3;6 that shows relatively early acquisition of both simple and complex forms
      of the passive. Within this age range children are productively producing
      truncated, full, action and experiential passives. Some possible reasons for this
      precociousness are explored including adult input and language structure.

PMID- 8733565
TI  - Eighteen-month-old children learn words in non-ostensive contexts.
AB  - Previous studies have demonstrated that children aged 2;0 can learn new words in
      a variety of non-ostensive contexts. The current two studies were aimed at seeing
      if this was also true of children just beginning to learn words at 1;6. In the
      first study an adult interacted with 48 children. She used a nonce word to
      announce her intention to find an object ('Let's find the gazzer'), picked up and
      rejected an object with obvious disappointment, and then gleefully found the
      target object (using no language). Children learned the new word as well in this
      condition as in a condition in which the adult found the object immediately. In
      the second study the adult first played several rounds of a finding game with
      each of 60 children, in which it was first established that one of several novel
      objects was always in a very distinctive hiding place (a toy barn). The adult
      then used a nonce word to announce her intention to find an object ('Let's find
      the toma') and then proceeded to the barn. In the key condition the barn was
      mysteriously 'locked'; the child thus never saw the target object after the nonce
      word was introduced. Children learned the new word as well in this condition as
      in a condition in which the adult found the object immediately. The results of
      these two studies suggest that from very early in language acquisition children
      learn words not through passive, associative processes, but rather through active
      attempts to understand adult behaviour in a variety of action and discourse
      contexts.

PMID- 8733566
TI  - Colour term knowledge in two-year-olds: evidence for early competence.
AB  - It is commonly believed that colour terms are acquired unusually slowly. However,
      several recent studies suggest that preschoolers have more colour term knowledge
      than previously believed. In two studies, we investigated the colour term
      knowledge of 49 two-year-olds and the influence of schooling on their colour term
      acquisition. Both studies revealed considerable knowledge in such young children.
      A longitudinal comparison of children with and without school experience in Study
      2 indicated that the higher performance of the school group could not be
      accounted for by differences predating that group's experience. In reviewing the
      evidence from the children's performance, we conclude that contemporary
      children's early and frequent experience with colour terms may account for this
      cohort's improved performance over previous generations of children.

PMID- 8733567
TI  - Developmental changes in the incidence and likelihood of simultaneous talk during
      the first two years: a question of function.
AB  - Global tendencies for the relative absence of covocalization (simultaneous talk)
      have been identified in both conversations between adult partners and
      conversations between mothers and their infants; in each case, the alternating
      mode in which one partner speaks at a time is predominant. The present
      investigation examined the timing of the partner's talk in mother-infant
      engagements over infant age to determine whether: (a) variations occur in the
      incidence of the alternating mode; and (b) variations occur in the extent to
      which the alternating mode predominates. Conversations involving a total of 48
      mothers and their infants aged from 0;3 to 2;0 were investigated at each of eight
      infant ages (0;3, 0;6, 0;9, 1;0, 1;3, 1;6, 1;9 and 2;0). The results indicated
      that, within a global tendency for the relative absence of covocalization, there
      was: (a) a curvilinear tendency for the incidence of covocalization to decrease
      over the first 18 months, and then to increase; and (b) a linear tendency for the
      extent to which the alternating mode predominates to increase over age. These
      changes are interpreted as reflecting the facilitative effects of covocalization
      in the case of young preverbal infants, and the need for the alternating, turn
      taking pattern to predominate as mutual comprehension becomes possible in
      conversations between mothers and their older infants.

PMID- 8733568
TI  - Competition on the face: affect and language in ASL motherese.
AB  - Research on early mother-child interaction has documented the crucial role affect
      plays in the content and modulation of early interactions. For hearing mothers,
      voice quality is considered to be the single most informative channel for
      affective expression. For deaf caregivers who use American Sign Language (ASL),
      the vocal channel is unavailable, and facial expression is critically important.
      Not only do facial behaviours signal affective and communicative information, but
      specific facial behaviours also function as obligatory grammatical markers. This
      multifunctionality of facial expression presents a dilemma for deaf parents
      signing to their toddlers as these two systems potentially compete for expression
      on the face. This study addresses how affective facial expression interacts with
      the linguistic forms in ASL motherese. To address this issue, we present data
      from both cross-sectional and longitudinal videotaped interaction from a total of
      15 deaf mothers signing with their deaf toddlers (ages 0;9-2;8). Using Ekman &
      Friesen's Facial Action Coding System (FACS) (1978) we analysed child-directed
      maternal wh- questions. Because they are frequent in early discourse, and they
      require furrowed brows which also signal anger and puzzlement, wh- questions
      represent an ideal context to address the potential conflict of grammatical and
      affective facial expression in ASL motherese. Our studies indicate a shift from
      affect to grammar at about the child's second birthday. These findings shed new
      insight on the nature and possible role of input on the language acquisition
      process.

PMID- 8733569
TI  - Measuring the vocabulary spurt: a reply to Mervis & Bertrand.
AB  - We reply to Mervis & Bertrand's report of three children (aged 1;6-1;8 at the
      start of the study) who evidenced a 'late' vocabulary spurt. Differences in
      assessing productive vocabulary, and the questionable inference that size of the
      lexicon is a reliable indicator of the vocabulary spurt, make it inappropriate to
      compare these children to previous studies that directly measure change in rate
      of word learning. Further work using continuous records of lexical development
      and controls for repeated cognitive assessments is needed to test hypotheses
      about the spurt and related cognitive and linguistic achievements.

PMID- 8733571
TI  - Endothelin-1 and the periaqueductal gray area of the rat: an autoradiographic and
      functional pharmacological study.
AB  - Endothelin-1 (ET-1) injected centrally induces pressor effects and associated
      haemodynamic changes. Here we have evaluated the effects on systemic and regional
      cardiovascular parameters of injection of ET-1 into the periaqueductal gray (PAG)
      area of anaesthetized rats. In addition, we have used the ETA receptor-selective
      antagonist, FR 139317, the ETB receptor-selective antagonist, BQ-788, and the
      ETA/ ETB receptor non-selective antagonist, SB 209670, to identify the
      receptor(s) mediating these effects. We have also used in vitro autoradiography
      to identify binding sites for ET-1 in the PAG. 2. In vitro autoradiography showed
      dense binding of [125I]-PD 151242 (for ETA receptors) in the PAG area, with the
      binding sites being homogeneously distributed within the dorsal, lateral and
      ventral subregions. Tissues incubated with [125I]-BQ 3020 (for ETB receptors) had
      little binding. 3. Injection of ET-1 (0.1, 1 and 10 pmol per rat) in the
      dorsolateral PAG area significantly increased, in a dose-dependent manner the
      mean arterial blood pressure (MAP). The highest dose of ET-1 (10 pmol) also
      decreased the heart rate by 18 +/- 1%, n = 6 (P < 0.05). Increases in blood
      pressure induced by ET-1 (1 pmol; 31 +/- 6.6 mmHg, n = 6) were greatly reduced by
      pre-administration to the PAG area of FR 139317 (5 nmol per rat) or SB 209670 (3
      nmol per rat) (97 and 94%, respectively), but were unaffected by BQ-788 (5 nmol
      per rat). Similarly, FR 139317 and SB 209670 prevented the decrease in heart rate
      induced by ET-1 while BQ-788 did not affect it. 4. Injection of ET-1 to the PAG
      area caused falls in renal blood flow (RBF) as measured by an ultrasonic flow
      probe, and increased renal vascular resistance (RVR). Pre-treatment of the PAG
      with FR 139317 or SB 209670, but not with BQ-788, prevented this ET-1-induced
      effect. 5. Injection of ET-1 (10 pmol) also increased total peripheral resistance
      (TPR; control, 2.39 +/- 0.2 mmHg ml-1 min 100 g body weight) by 100 +/- 9% (n =
      5) and reduced the cardiac output (CO; control, 94.7 +/- 3.1 ml min-1) by 30 +/-
      3% (n = 5), as determined by radioactive microspheres. Vascular resistances were
      increased in other organs, such as skeletal muscle (88 +/- 5%, n = 4), the colon
      (55 +/- 7%, n = 4) and the stomach (47 +/- 3%, n = 4). Pretreatment of the PAG
      area with FR 139317 or SB 209670 reduced the increases in TPR and vascular
      resistance, and the reduction in CO caused by ET-1. BQ-788 did not effect the
      responses to ET-1. 6. Thus, there are predominantly ETA binding sites within the
      PAG area and injection of ET-1 into the PAG area causes complex haemodynamic
      changes which are sensitive to ETA receptor antagonism. ETA receptors are,
      therefore, the predominant mediators of the actions of ET-1 in the PAG of the
      rat.

PMID- 8733570
TI  - Fifteenth Gaddum Memorial Lecture December 1994. Stress and the neuroendocrine
      immune axis: the pivotal role of glucocorticoids and lipocortin 1.

PMID- 8733572
TI  - Relative potencies of metal ions on transmitter release at mouse motor nerve
      terminals.
AB  - 1. The effects of a range of metal ions were systematically studied at the mouse
      neuromuscular junction in order to investigate the type of calcium channel
      present at the nerve terminal. 2. Endplate potentials and miniature endplate
      potentials were recorded from the phrenic nerve diaphragm muscle preparation with
      glass microelectrodes. 3. Endplate potential amplitudes and quantal contents were
      reduced by manganese (IC50 220 microM), cadmium (IC50 11 microM), cobalt (IC50
      350 microM), and nickel (IC50 420 microM). Miniature endplate potentials were not
      affected by these ions at concentrations equal to the IC50s. Gadolinium did not
      reduce endplate potentials up to 100 microM. 4. Comparisons made with known
      channel types in neuroblastoma cell lines suggest that the calcium channels at
      the motor nerve terminal are different from those types studied in the cell
      lines, although most similarity is shown to the high-voltage activated calcium
      channel types.

PMID- 8733573
TI  - Effects of delayed treatment with nafronyl oxalate on microsphere embolism
      induced changes in monoamine levels of rat brain regions.
AB  - 1. The present study was undertaken to examine the effects of delayed treatment
      with nafronyl oxalate (nafronyl), a cerebral vasodilator, on monoamine
      neurotransmitters of brain regions in the microsphere-embolized rat. 2.
      Microsphere embolism was induced by injecting 900 microspheres with a diameter of
      48 microns into the right internal carotid artery of rats. Microsphere-embolized
      rats were treated with nafronyl, 15 mg kg-1, i.p., twice daily from the first to
      the 5th day. Levels of monoamines and their metabolites in the cerebral cortex,
      striatum, and hippocampus were measured on days 3 and 5 after the operation by a
      high-performance liquid chromatograph with electrochemical detection. In vivo
      tyrosine or tryptophan hydroxylation was estimated by measurement of the
      accumulation of 3, 4-dihydroxyphenylalanine or 5-hydroxy-1-tryptophan after
      administration of 3-hydroxybenzylhydrazine dihydrochloride, an inhibitor of
      aromatic L-amino acid decarboxylase. 3. Microsphere embolism induced decreases in
      dopamine, noradrenaline and 5-hydroxytryptamine in three brain regions of the
      right hemisphere on days 3 and 5. In the left hemisphere, the monoamines were
      reduced, but to a lesser degree than in the right hemisphere. On days 3 and 5,
      the decrease in the monoamines of the right hemisphere was attenuated by nafronyl
      treatment except for noradrenaline on day 3. The decrease in the monoamines
      levels in the left hemisphere was almost completely prevented by nafronyl
      treatment. 4. On day 3 after microsphere embolism, in vivo tyrosine and
      tryptophan hydroxylation was lower than the pre-embolic value in all three brain
      regions. Treatment of the embolized rats with nafronyl significantly attenuated
      the decrease in in vivo tyrosine and tryptophan hydroxylation in the ipsilateral
      hemisphere, but not hippocampal tryptophan hydroxylation. 5. The results
      suggested that treatment with nafronyl improves or attenuates changes in
      monoamine neurotransmitter metabolism of the brain regions impaired by
      microsphere embolism. The mechanisms underlying this effect may be attributed to
      preservation of the ability to synthesize monoamines when the brain is ischaemic
      or oligaemic.

PMID- 8733574
TI  - Blockade of swelling-induced chloride channels by phenol derivatives.
AB  - 1. In NIH3T3 fibroblasts, the chloride channel involved in regulatory volume
      decrease (RVD) was identified as ICln, a protein isolated from a cDNA library
      derived from Madin Darby canine Kidney (MDCK) cells. ICln expressed in Xenopus
      laevis oocytes gives rise to an outwardly rectifying chloride current, sensitive
      to the extracellular addition of nucleotides and the known chloride channel
      blockers, DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) and NPPB (5
      nitro-2-(3-phenylpropylamino)-benzoic acid). We set out to study whether
      substances structurally similar to NPPB are able to interfere with RVD. 2. RVD in
      NIH3T3 fibroblasts and MDCK cells is temperature-dependent. 3. RVD, the swelling
      dependent chloride current and the depolarization seen after reducing
      extracellular osmolarity can be blocked by gossypol and NDGA
      (nordihydroguaiaretic acid), both structurally related to NPPB. 4. The cyclic AMP
      dependent chloride current elicited in CaCo cells is less sensitive to the two
      substances tested while the calcium-activated chloride current in fibroblasts is
      insensitive. 5. The binding site for the two phenol derivatives onto ICln seems
      to be distinct but closely related to the nucleotide binding site identified as G
      x G x G, a glycine repeat located at the predicted outer mouth of the ICln
      channel protein.

PMID- 8733575
TI  - Hyperpolarization and inhibition of contraction mediated by nitric oxide released
      from enteric inhibitory neurones in guinea-pig taenia coli.
AB  - 1. Inhibition of nitric oxide synthase by NG-nitro-L-arginine (L-NNA) reduced the
      neurogenic relaxation of precontracted taenia coli only in the absence of
      atropine. The membrane hyperpolarization associated with the neurogenic
      relaxation was also reduced by inhibition of NOS only when atropine was absent.
      2. The membrane hyperpolarization associated with the neurogenic relaxation of
      the taenia coli was inhibited by oxyhaemoglobin only in the absence of atropine.
      In the presence of atropine, oxyhaemoglobin did not reduce the i.j.p. or nerve
      evoked relaxation. 3. Inhibition of NOS by L-NNA did not affect the overflow of
      [3H]-ACh in response to electrical field stimulation (EFS), suggesting that,
      under the conditions of our experiments, endogenous NO did not modulate release
      of ACh. Sodium nitroprusside also had no effect on the neurogenic overflow of
      [3H]-ACh; however, noradrenaline significantly reduced [3H]-ACh overflow. 4. In
      summary, the postjunctional effects of neurally-released NO are not apparent in
      guinea-pig taenia coli when atropine is present. This implies muscarinic
      regulation of NO release or muscarinic regulation of another excitatory
      substance, such as tachykinin(s), that, when blocked, masks the postjunctional
      effects of NO. These data, together with previous studies, suggest a possible
      regulatory role for NO in enteric neurotransmission that may be more prominent in
      some species or tissues than others.

PMID- 8733576
TI  - Inhibition of NO-medicate responses by 7-ethoxyresorufin, a substrate and
      competitive inhibitor of cytochrome P450.
AB  - 1. The effects of 7-ethoxyresorufin (7-ER), which is a substrate for and
      competitive inhibitor of cytochrome P450, were studied on responses to nitric
      oxide (NO), the NO donors sodium nitroprusside (SNP) and glyceryl trinitrate
      (GTN), acetylcholine-induced endothelium-dependent relaxations of rat and rabbit
      aortic rings and nitrergic nerve stimulation-induced relaxations of rat
      anococcygeus muscles. 2. In rat and rabbit aortic rings, 7-ER (2 microM)
      inhibited the relaxations to acetylcholine in endothelium-intact preparations and
      the relaxant action of NO in endothelium-denuded preparations. Relaxant responses
      to SNP and GTN were inhibited by 7-ER in the rat but not rabbit aortic rings.
      However, the relaxant actions of papaverine and 8-bromo-cyclic GMP were not
      affected by 7-ER. 3. In rat anococcygeus muscles, 7ER (2 microM) inhibited the
      relaxant action of NO, but relaxations elicited by nitrergic nerve stimulation
      were only partly inhibited by a higher concentration of 7-ER (10 microM). 4.
      After inhibition by 7-ER, superoxide dismutase (100 u ml-1) restored NO-induced
      relaxations of the rat aortic rings, but not acetylcholine-, SNP or GTN-induced
      relaxations, and restored NO- and nitrergic nerve stimulation-induced relaxations
      of anococcygeus muscles. 5. Another cytochrome P450 inhibitor, troleandomycin (10
      30 microM), had no effect on NO- or acetylcholine-induced relaxations of rat
      aortic rings and NO- or nitrergic nerve stimulation-induced relaxations of
      anococcygeus muscles. However, resorufin, an analogue of 7-ER, inhibited
      responses to acetylcholine, NO and GTN in rat aortic rings. 6. The results
      suggest that 7-ER inhibited responses to NO and nitrergic nerve stimulation
      through generation of superoxide radicals. However, an additional mechanism may
      be involved in the reduction in acetylcholine-induced response in aortic rings.
      7. A 7-ER sensitive P450 system may be involved in the bioactivation of GTN and
      SNP in rat aortic rings, but not in rabbit aorta or rat anococcygeus muscles.

PMID- 8733577
TI  - Modulation of sexual behaviour in the rat by a potent and selective alpha 2
      adrenoceptor antagonist, delequamine (RS-15385-197).
AB  - 1. The contributions of alpha 2-adrenoceptors and 5-HT1A receptors to sexual
      behaviour in the rat have been re-evaluated by use of a highly potent and
      selective alpha 2-adrenoceptor antagonist, delequamine (RS-15385-197), yohimbine,
      idazoxan and the partial agonist at 5-HT1A receptors, 8-hydroxy-2(di-n
      propylamino)-tetralin (8-OH-DPAT). 2. In a model where naive male rats were
      introduced to oestrogen-progesterone primed, sexually receptive female rats,
      delequamine (0.4-6.4 mg kg-1, p.o.) dose-relatedly increased the sexual behaviour
      score over the entire dose-range whereas yohimbine was effective at only one
      dose, 2 mg kg-1, p.o.. Idazoxan was active only at 2.5 and 5 mg kg-1, p.o.
      Yohimbine, but neither delequamine nor idazoxan, decreased ejaculation latency. 8
      OH-DPAT (0.1 and 0.25 mg kg-1, s.c.) reduced the time, and the number of
      intromissions to ejaculation without affecting other parameters. A combination of
      delequamine (0.4 mg kg-1, p.o.) and 8-OH-DPAT (0.1 mg kg-1 s.c.) increased the
      percentage of rats mounting, intromitting and ejaculating, and reduced
      ejaculation latency and the number of intromissions. 3. In orchidectomized,
      sexually experienced rats exposed to sexually receptive females, delequamine,
      idazoxan and yohimbine increased the number of rats mounting, and there was a
      tendency to increase the number of animals intromitting, but no effect on
      ejaculatory behaviour. 4. In ovariectomized female rats brought to low level
      receptivity by priming with low dose injections of oestradiol benzoate and
      progesterone, delequamine, at 1.6 and 6.4 mg kg-1 p.o., increased lordosis, while
      yohimbine, at 2, 4 and 8 mg kg-1 p.o., reduced lordotic responses to sexually
      experienced males in a dose-dependent manner. 8-OH-DPAT at 0.1, 0.25 mg kg-1,
      s.c. reduced lordosis in a dose-dependent manner. 5. These findings may be
      explained on the basis that yohimbine is an alpha 2-adrenoceptor antagonist with
      affinity for 5-HT1A receptors and that the effects of 5-HT1A receptors may
      modulate the sexual behaviour responses to alpha 2-receptor antagonism in some
      models. Thus, in contrast to yohimbine, the highly-selective alpha 2-adrenoceptor
      antagonist, delequamine, was very effective in increasing the behavioural score
      in male and female rats over a wide dose-range.

PMID- 8733578
TI  - Angiotensin II-activated Ca2+ entry-induced release of Ca2+ from intracellular
      stores in rat portal vein myocytes.
AB  - 1. The action of angiotensin II (AII) was studied in single myocytes from rat
      portal vein in which the cytoplasmic Ca2+ concentration was estimated by emission
      from dyes Fura-2 or Indo-1 and the Ca2+ channel current was measured with the
      whole-cell mode of the patch-clamp technique. 2. Most of the AII-evoked increases
      in [Ca2+]i were reduced by about 60% after pretreatment with ryanodine and
      caffeine to deplete intracellular Ca2+ stores. However, in some cells the AII
      induced Ca2+ responses were of small amplitude and resembled those obtained in
      the presence of ryanodine and caffeine. Both types of Ca2+ responses induced by
      AII were selectively inhibited by losartan, suggesting that the AII effects
      resulted from activation of the angiotensin AT1 receptors. 3. The concentration
      response curve to AII had an EC50 value close to 1 nM for the increase in [Ca2+]i
      obtained after depletion of intracellular Ca2+ stores. This value was increased
      to around 18 nM in experiments where the intracellular Ca2+ stores were not
      depleted. 4. AII-evoked Ca2+ responses were abolished in the absence of external
      Ca2+ and in the presence of 1 microM oxodipine to block L-type Ca2+ channels. 5.
      Intracellular applications of the InsP3 receptor antagonist, heparin or an anti
      PdtIns antibody did not modify AII-induced Ca2+ responses. 6. Our results show
      that AII releases Ca2+ from intracellular stores without involving InsP3 but
      through a Ca2+ release mechanism activated by Ca2+ influx through L-type Ca2+
      channels.

PMID- 8733579
TI  - Angiotensin II-elicited signal transduction via AT1 receptors in endothelial
      cells.
AB  - 1. Angiotensin II (AII) actions are mediated by two distinct types of receptors:
      AT1, which includes two subtypes, AT1A and AT1B, and AT2. AII produces
      vasoconstriction on the vascular wall acting directly on smooth muscle cells via
      AT1 receptors. AII receptors have recently been demonstrated on endothelial
      cells. But the pharmacological characteristics of these receptors and the
      intracellular signal pathways coupled to them remain unclear. 2. The aim of this
      work was to characterize the AII receptor subtypes in rat aortic endothelial
      cells (RAEC) in primary culture and to evaluate the signal pathways coupled to
      these receptors by measuring the activation of phospholipase C (PLC) and
      phospholipase A2 (PLA2). 3. Labelled AII bound to RAEC in a specific, saturable
      manner. Scatchard analysis showed a Kd of 1.87 +/- 0.49 nM and a Bmax of 50.2 +/-
      10.9 x 10(3) sites per cell. AII was displaced by the AT1-specific antagonist,
      DuP753 with a Ki of 17.37 +/- 1.49 nM, but not by the AT2 receptor analogues
      CGP42771B or PD123177. These data were confirmed by the finding of AT1 mRNA in
      endothelial cells. Analysis of RNA expression by RT-PCR showed the presence of
      both subtypes, AT1A and AT1B in endothelial cells, whereas smooth muscle cells
      express only AT1A. 4. The activation of PLC and PLA2 in response to AII was
      evaluated by measuring inositol phosphate production and arachidonic acid
      release, respectively. Both were enhanced by AII in a dose-dependent manner, and
      inhibited by DuP753, but not by PD123177. 5. We conclude that AT1 receptors are
      expressed by endothelial cells in primary culture and that phospholipase C and
      phospholipase A2 activated via this receptor.

PMID- 8733580
TI  - Blockade of porcine carotid vascular response to sumatriptan by GR 127935, a
      selective 5-HT1D receptor antagonist.
AB  - 1. It has previously been shown that the antimigraine drug, sumatriptan, a
      putative 5-HT1D receptor agonist, decreases porcine common carotid and
      arteriovenous anastomotic blood flows, but slightly increases the arteriolar
      (capillary) blood flow to the skin and ears. Interestingly, such responses, being
      mediated by 5-HT1-like receptors, are resistant to blockade by metergoline,
      which, in addition to displaying a very high affinity for (and occasionally
      intrinsic efficacy at) the 5-HT1D receptor subtypes, blocks (with lower potency
      than methiothepin) some 5-HT1D receptor-mediated vascular responses. These
      findings raise doubts whether sumatriptan-sensitive 5-HT1-like receptors
      mediating changes in the distribution of porcine carotid blood flow are identical
      to cloned 5-HT1D receptors. With the recent advent of the potent and selective 5
      HT1D receptor antagonist, GR127935, we have examined in the present study whether
      the carotid vascular effects of sumatriptan in the pig are amenable to blockade
      by GR127935. 2. In animals pretreated with saline, sumatriptan (30, 100 and 300
      micrograms kg-1, i.v.) reduced the total carotid and arteriovenous anastomotic
      blood flows in a dose dependent manner. In contrast, sumatriptan increased blood
      flow to the skin, ears and fat, although the total capillary fraction was not
      significantly affected. 3. While GR127935 pretreatment (0.25 and 0.5 mg kg-1)
      itself slightly reduced the total carotid and arteriovenous anastomotic blood
      flows, carotid vasoconstrictor responses to sumatriptan were either partly (0.25
      mg kg-1) or completely (0.5 mg kg-1) blocked by the compound. In GR127935
      pretreated animals, the sumatriptan-induced increases in blood flow to the skin,
      ears and fat were also attenuated. 4. Taken together, the results suggest that
      arteriovenous anastomotic constriction and, possibly, arteriolar dilatation in
      the skin, ears and fat by sumatriptan are mediated by 5-HT1D receptors.
      Therefore, vascular 5-HT1-like receptors in the porcine carotid bed appear to be
      identical to 5-HT1D receptors.

PMID- 8733581
TI  - Baroreflex resetting but no vascular tolerance in response to transdermal
      glyceryl trinitrate in conscious rabbits.
AB  - 1. We investigated whether acute (5 h) and chronic (3 days) transdermal glyceryl
      trinitrate (GTN) patches could cause the development of tolerance in terms of
      haemodynamics and vascular reactivity in the conscious rabbit. The effects of
      haemodynamic tolerance were assessed on arterial pressure, heart rate and the
      baroreflex control of heart rate, while hindquarter vascular reactivity in
      response to dilator and constrictor drugs and reactive hyperaemia were used to
      assess vascular tolerance. 2. Seven days prior to experiments, an inflatable
      cuff, a pulsed Doppler flow probe and an indwelling intra-aortic catheter (for
      i.a. agonist infusions) were implanted around the lower abdominal aorta. 3. In
      acute experiments, the effects of 0-5 h treatment with transdermal GTN (0 Sham),
      10 or 20 mg 24 h-1) on MAP, HR and the baroreflex were examined. Chronic
      experiments were performed on three separated days (days 0 - before, 4 - with GTN
      patch and 8 - recovery). On each day, the baroreflex, reactive hyperaemic
      responses and hindquarter vascular dose-response curves to i.a. GTN, adenosine,
      acetylcholine, S-nitroso-N-acetylpenicillamine (SNAP) and methoxamine were
      assessed. On days 1-4, GTN was administered transdermally via a patch(es) (10 mg
      24 h-1 (low dose) or 20 mg 24 h-1 (high dose); renewed every 24 h). 4. Acute
      treatment with 20 mg GTN 24 h-1, but not with 0 (n = 4) or 10 mg GTN 24 h-1 (n =
      4), caused a significant fall in MAP (8 +/- 1 mmHg; n = 4) and resetting of the
      baroreflex by 5 h. Chronic GTN caused a significant fall in MAP of 8 +/- 2 and 8
      +/- 2 mmHg on day 4 with low (n = 8) and high dose (n = 8), respectively, with no
      change in HR. There was no significant change to hindquarter vascular reactivity
      to i.a. infusion of GTN, nor were there any significant differences in the
      reactivity to i.a. adenosine, acetylcholine, SNAP or methoxamine with either low
      or high doses of GTN. 5. Chronic GTN treatment with low and high dose patches
      caused a parallel leftward shift ('resetting') of the baroreflex on day 4. By day
      8, the baroreflex had still not recovered from this leftward shift 6. In the
      rabbit, chronic exposure to clinical nitrate patches caused haemodynamic
      compensation and baroreflex resetting but no evidence of vascular reactivity
      tolerance. Novel NO donor drugs and delivery regimens which provide intermittent
      dosing may prevent the development of haemodynamic resetting rather then
      preventing vascular tolerance, a commonly perceived difficulty in chronic nitrate
      therapy.

PMID- 8733582
TI  - Two types of ATP-sensitive potassium channels in rat portal vein smooth muscle
      cells.
AB  - 1. Single-channel recordings were made from single, enzymatically isolated smooth
      muscle cells of rat portal vein by the patch-clamp technique. 2. Unitary
      potassium currents were identified through two types of K-channels with
      conductances in 60:130 mM K-gradient of 50 and 22 pS; these are referred to as LK
      and MK channels respectively. 3. The LK channels became extremely active if
      isolated patches were created into nucleotide-free solution; activity was
      inhibited by ATP applied to the inner surface of the patch with a half maximal
      inhibition (Ki) of 11-23 microM. Channel activity declined and disappeared with
      time and could be regenerated by a brief application of Mg-ATP or a nucleoside
      diphosphate such as UDP (in the presence of Mg). LK channel activity was rarely
      stimulated by levcromakalim and not by pinacidil (K-channel openers, KCOs) but
      was blocked by glibenclamide. 4. Activity of MK channels declined if isolated
      patches were created into nucleotide free solution; activity reappeared if UDP or
      ATP alone (in the presence of Mg) was applied; pinacidil or levcromakalim in the
      presence of ATP or UDP further increased channel activity which was blocked by
      glibenclamide. 5. The LK channel inhibited by ATPi is very similar in its
      conductance and other properties to the KATP channel described in tissues other
      than smooth muscle, in its conductance and properties the MK channel resembles
      the KNDP channel we have previous described as present in other smooth muscles
      and opening in responses to KCOs.

PMID- 8733583
TI  - Enhanced contractile responses of arteries from streptozotocin diabetic rats to
      sodium fluoride.
AB  - 1. Previous studies from this laboratory have demonstrated that alpha 1
      adrenoceptor-mediated increases in tension and phosphoinositide metabolism are
      enhanced in the aorta and mesenteric arteries from diabetic rats. The purpose of
      the present investigation was to determine whether contractile responses to
      sodium fluoride (NaF), which directly stimulates GTP-binding proteins (G
      proteins), are also enhanced in diabetic arteries. 2. NaF (1-20 mM) in the
      presence of 10 microM aluminium chloride produced slowly developing,
      concentration-dependent contractions in mesenteric arteries from three month
      streptozotocin-diabetic (60 mg kg-1, i.v.) male Wistar rats and age-matched
      control rats. The maximum contractile response but not the sensitivity to NaF was
      significantly greater in mesenteric arteries from diabetic than from control
      rats, as was the response to noradrenaline (NA). Maximum contractile responses of
      aorta and caudal artery from diabetic rats to NaF were also significantly
      enhanced. 3. Removal of the endothelium and denervation with 6-hydroxydopamine
      did not significantly alter the maximum contractile response of mesenteric
      arteries from either control or diabetic rats to NaF. Similarly, NaF had no
      effect on cyclic AMP levels in aorta, and no difference in cyclic AMP levels,
      either basally or in the presence of NaF, was detected between control and
      diabetic rat aorta. 4. Contractile responses of mesenteric arteries from both
      control and diabetic rats to NaF were diminished in calcium-free Krebs solution,
      but the NaF response remained significantly elevated in mesenteric arteries from
      diabetic rats compared to control. 5. Ryanodine (30 microM) which depletes
      intracellular calcium stores, nifedipine (3 microM) which blocks dihydropyridine
      sensitive calcium channels and calphostin C (0.5 microM) which selectively
      inhibits protein kinase C, all significantly inhibited maximum contractile
      responses of mesenteric arteries from control and diabetic rats to NaF. There
      were no significant differences between control and diabetic arteries in the
      relative magnitude of the inhibition produce by the three antagonist. 6. These
      data suggest that there may be increased activation of the same signalling
      processes that mediate NA-stimulated vasoconstriction, perhaps contraction
      associated G-proteins or the effectors coupled to these G-proteins, in response
      to NaF in mesenteric arteries from diabetic rats. This may also be responsible
      for the enhanced contractile responses of these arteries to alpha 1-adrenoceptor
      stimulation.

PMID- 8733584
TI  - Protein kinase C isoforms in bovine aortic endothelial cells: role in regulation
      of P2Y- and P2U-purinoceptor-stimulated prostacyclin release.
AB  - 1. Enhanced synthesis of prostacyclin (PGI2) and inositol polyphosphates in
      bovine aortic endothelial cells in response to ATP and ADP is mediated by co
      existing P2Y- and P2U-purinoceptors. Here we examine the regulation of these
      responses by isoforms of protein kinase C (PKC). 2. Immunoblots with antisera
      specific for 8 different PKC isoforms revealed the presence of alpha, epsilon and
      zeta, while no immunoreactivity was found for beta, gamma, delta, eta and theta
      isoforms. PKC-alpha was largely cytosolic in unstimulated cells and almost all
      translocated to the membrane (Triton X-100 soluble) after a 1 min treatment with
      the PKC activating phorbol myristate acetate (PMA); PKC-epsilon was always in a
      Triton X-100 insoluble membrane fraction, while PKC-zeta was found in both
      soluble and membrane bound (Triton X-100 soluble) forms in the unstimulated cells
      and was unaffected by PMA. 3. Treatment with PMA for 6 h led to a 90%
      downregulation of PKC-alpha, while the immunoreactivity to the epsilon and zeta
      isoforms remained largely unchanged. 4. After either 10 min or 6 h exposure to
      PMA the PGI2 response to activation of both receptors was enhanced, while the
      inositol 1,4,5-trisphosphate response to P2Y-purinoceptor activation was
      substantially attenuated and the P2U-purinoceptor response was unchanged. Thus
      the PGI2 response to PMA under conditions when 90% of the PKC-alpha was lost
      resembles that seen on acute stimulation of PKC by PMA, and the PGI2 response
      does not correlate with phospholipase C response. 5. Inhibition of PKC with the
      isoform non-selective inhibitors, Ro 31-8220 and Go 6850 abolished the PGI2
      response to both P2U- and P2Y-purinoceptor stimulation. However, Go 6976, which
      preferentially inhibits Ca2+ sensitive isoforms (such as PKC-alpha) and not Ca2+
      insensitive isoforms (such as PKC-epsilon), had no effect on the PGI2 response.
      6. The results show that there is a requirement for PKC in the stimulation of
      PGI2 production by endothelial P2Y- and P2U-purinoceptors. Both downregulation
      and inhibition studies show that PKC-alpha is not responsible for the regulation
      of the response to P2-purinergic stimulation, and imply that the response is
      mediated by PKC-epsilon (PKC-zeta is unresponsive to PMA), or an as yet
      uncharacterized PKC isoform.

PMID- 8733585
TI  - Effects of phosphorothioated neuropeptide Y Y1-receptor antisense
      oligodeoxynucleotide in conscious rats and in human vessels.
AB  - 1. Metabolically stabilized (phosphorothioate) human and rat NPY Y1 receptor
      oligodeoxynucleotides (ODNs) complimentary to the rat or human Y1 mRNA were
      synthesized; [sense (rY1-SODN, 5'-AATTCAACTCTGTTCTCC-3'), antisense (hY1-ASODN,
      5'-CCTGGGAAAATAATGTTG-3' and rY1-ASODN, 5'-GGAGAACAGAGTTGAATT-3') and mismatches
      (hY1-MMODN, 5'-CCTGAGATAA-TAAGGTTG-3' and rY1-MM 5'-GTAGATCAGAGATGAAGT-3')] and
      used to modulate cardiovascular function in vitro in human vessels as well as in
      vivo in the rat. 2. The objectives of the experiments were to assess the
      influence of the NPY Y1 receptor on vasomotor function human resistance arteries
      in vitro and to investigate the contribution of the NPY receptor system to
      cardiovascular haemodynamics in vivo. 3. Human subcutaneous resistance arteries
      removed from patients who underwent surgery for nonvascular diseases were
      incubated in vitro with the stabilized phosphorothioated hY1-receptor ASODN or
      MMODN (10(-7) TO 10(-5) M). 4. In human resistance vessels preincubated with hY1
      AS (10(-7) to 10(-5) M), the contractile response to NPY was significantly
      reduced in a dose-dependent fashion. No effects were observed in the hY1-MMODN
      incubated vessels at lower concentrations (10(-7) M to 10(-6) M). 5. The
      haemodynamic effects of the phosphorothioated rY1-ASODN, SODN or MMODN were
      investigated in conscious rats during 48 h of continuous infusions. The
      continuous infusion with rY1-ASODN did not change MAP while the rY1-SODN
      unexpectedly induced an early (10-20) increase in ambulatory MAP and the rY1
      MMODN a late (24-44 h) increase. 6. Contractile responses to NPY (2, 4, 8, 16 and
      32 micrograms kg-1) were significantly reduced in the rats treated with long-term
      infusion of rY1-ASODN (2.1 mg kg-1 h-1, i.v. infusion for 48 h) compared with
      animals treated with rY1-SODN and MMODN, as well as animals treated with saline
      and glucose. Notably, the group infused with the rY1-SODN showed an exaggerated
      response to tested doses of NPY. 7. We conclude that the incubation of human
      subcutaneous arteries with a metabolically stabilized 18 base pair hY1-ASODN and
      long-term infusion with a corresponding rY1-ASODN attenuate NPY-induced
      vasoconstriction.

PMID- 8733586
TI  - Inhibition of nitrergic relaxations by a selective inhibitor of the soluble
      guanylate cyclase.
AB  - 1. The actions of 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ), a specific
      inhibitor of the soluble guanylate cyclase (SGC), were investigated in the rabbit
      anococcygeus muscle. 2. ODQ (1 nM-1 microM) inhibited in a concentration
      dependent manner the relaxations induced by electrical field stimulation (EFS; 50
      V, 0.3 ms duration, 1 Hz, for 5 s, every 120 s). 3. ODQ (1 microM) also inhibited
      the relaxations elicited by EFS (50 V, 0.3 ms duration, 1, 2.5, 5, 10 Hz, for 5
      s) and sodium nitroprusside (SNP; 1 microM) without affecting those induced by
      isoprenaline (1 microM), atrial natriuretic peptide (ANP; 100 nM) or an analogue
      of cyclic GMP (8-pCPT-cyclic GMP; 500 microM). 4. ODQ (1 microM) inhibited the
      elevations in the concentration of cyclic GMP induced by SNP or EFS, but not by
      ANP. ODQ did not affect the concentrations of cyclic AMP. 5. Nitrergic relaxation
      in this tissue appears, therefore, to be mediated via activation of SGC.

PMID- 8733587
TI  - Effects of dexamethasone and SB 209670 on the regional haemodynamic responses to
      lipopolysaccharide in conscious rats.
AB  - 1. Male (350-450 g) Long Evans rats were chronically instrumented to permit
      regional haemodynamics to be monitored in the conscious state. In the first
      experiment, either saline (0.4 ml h-1) or dexamethasone (3 mg kg-1, 125
      micrograms kg-1 h-1) was infused continuously for 24 h, before co-infusion of
      lipopolysaccharide of (LPS, 150 micrograms kg-1 h-1) for 24 h. Dexamethasone
      prevented the delayed (5-24 h) fall in mean arterial blood pressure (MAP) and the
      renal and hindquarters vasodilatation seen with LPS infusion alone, but not the
      initial (about 2 h) fall in MAP or renal vasodilatation. However, at this dose,
      dexamethasone itself caused a significant rise in MAP and regional
      vasoconstrictions. 2. In the second experiment, dexamethasone at a lower dose
      (12.5 micrograms kg-1 h-1) had only slight pressor and vasoconstrictor effects.
      However, in its presence, infusion of LPS caused a substantial and progressive
      rise in MAP (maximum at 8 h, +32 +/- 3 mmHg) together with persistent mesenteric
      and hindquarters vasoconstriction and a transient renal vasodilatation. 3. In the
      third experiment, the non-selective endothelin antagonist, SB 209670 (600
      micrograms kg-1 h-1), blocked the slight pressor and regional vasoconstrictor
      effects of the lower dose of dexamethasone. Furthermore, in the presence of
      dexamethasone and SB 209670, infusion of LPS caused marked, but transient
      hypotension (nadir at 5 h, -24 +/- 2 mmHg) and renal and mesenteric
      vasodilatation. 4. At the end of all experimental protocols, sequential
      administration of the AT1-receptor antagonist, losartan, followed by the V1
      receptor antagonist, (+)-(CH2)5-O-Me-Tyr, vasopressin, caused effects indicating
      a variable involvement of angiotensin and vasopressin in the maintenance of
      cardiovascular status. 5. Collectively, the results indicate that, in the
      conscious rat, dexamethasone interacts with vasoconstrictor and vasodilator
      mechanisms, and hence its influence on the haemodynamic responses to LPS cannot
      be attributed, simply, to inhibition of the activity of inducible nitric oxide
      synthase and/or cyclo-oxygenase-2.

PMID- 8733588
TI  - Spinal 5-HT2 receptor-mediated facilitation of pudendal nerve reflexes in the
      anaesthetized cat.
AB  - 1. 5-Hydroxytryptamine (5-HT) is intimately associated with central sympathetic
      and somatic control of the lower urinary tract. The sympathetic and somatic
      innervation of the lower urinary tract is conveyed through efferent axons of the
      hypogastric and pudendal nerves, respectively. 2. The present study examined the
      effects of 2,5-dimethoxy-4-iodophenylisopropylamine (DOI), a 5-HT2 receptor
      subtype-selective agonist, on evoked potentials recorded from the central ends of
      the hypogastric and pudendal nerves in response to electrical stimulation of
      afferent fibres in the pelvic and pudendal nerves, respectively. Various
      spinalization paradigms were employed to localize the site of action. All cats
      were pretreated with xylamidine (1 mg kg-1), a peripherally-restricted 5-HT2
      receptor antagonist. 3. In acute spinal cats, DOI (0.01-3 mg kg-1, i.v.) reliably
      produced dose-dependent increases in the pudendal nerve reflex (to 228 +/- 31% of
      control). These increases were reversed by the 5-HT2 receptor-selective
      antagonist, LY53857 (0.3-3 mg kg-1, i.v.). On the other hand, in spinally-intact
      cats, DOI produced no significant changes in the pudendal reflex. However, within
      minutes of spinalization of DOI-pretreated cats, a marked increase (to 221 +/-
      16% of control) in the pudendal reflex was observed which could be reversed by
      LY53857. No significant effects were observed on hypogastric reflexes in either
      acute spinal or spinally-intact cats following DOI administration. No effects
      were seen in either spinally-intact or acute spinal animals when LY53857 was
      administered as the initial drug. 4. These results indicate that activation of
      spinal 5-HT2 receptors facilitates pudendal reflexes. In spinally-intact cats, it
      is hypothesized that DOI activates supraspinal pathways that mediate inhibition
      of the pudendal reflexes and counteracts the facilitatory effects of spinal 5-HT2
      receptor activation.

PMID- 8733590
TI  - Inhibition by lifarizine of intracellular Ca2+ rises and glutamate exocytosis in
      depolarized rat cerebrocortical synaptosomes and cultured neurones.
AB  - 1. The effects of lifarizine (RS-87476) on intracellular Ca2+ rises and the
      release of glutamate from rat cerebrocortical synaptosomes depolarized with 30 mM
      KCl were investigated by use of entrapped fura 2 and exogenous glutamate
      dehydrogenase. 2. Prior (1 min) addition of lifarizine decreased 30 mM KCl
      induced total glutamate release, with 3 microM and 10 microM causing 39% and 72%
      averaged decreases from controls. The calcium-dependent component of glutamate
      release (approx. 40% of total) was similarly decreased by 47% and 74%, whereas
      the calcium-independent component was decreased by only 32% and 43% respectively.
      3. In parallel experiments with fura-2-loaded synaptosomes, lifarizine reduced
      the depolarization-induced increases in intracellular [Ca2+], suggesting that
      this is the means by which the decreases in glutamate release are brought about.
      Lifarizine inhibited both the plateau and the spike phases of the Ca2+ increases
      suggesting that, in addition to its known sodium channel blocking properties, it
      may also inhibit more than one class of calcium channel in the synaptosomes. 4.
      Lifarizine at 1 microM and 3 microM also inhibited the rises in intracellular
      [Ca2+] in rat cultured cortical neurons depolarized with 60 mM KCl. 5. These
      effects of lifarizine on intracellular Ca2+ and glutamate exocytosis may
      contribute to its neuroprotective action.

PMID- 8733589
TI  - Nitric oxide as a mediator of cocaine-induced penile erection in the rat.
AB  - 1. The effect of local application of cocaine to the corpus cavernosum on
      intracavernous pressure (ICP), an experimental index for penile erection, was
      examined in Sprague-Dawley rats anaesthetized with chloral hydrate. The potential
      involvement of dopamine, noradrenaline or nitric oxide as the chemical mediator
      in this process, and the pharmacological action of cocaine as a local anaesthetic
      in the induced increase in ICP, were also investigated. 2. Intracavernous (i.c.)
      administration of cocaine (40, 80 or 160 micrograms) to the corpus cavernosum
      resulted in a dose-related increase in both amplitude and duration of ICP. 3. The
      elevation of ICP induced by cocaine (160 micrograms, i.c.) was not significantly
      influenced by prior injection into the corpus cavernosum of either the D1 or D2
      dopamine receptor antagonist, R-(+)-SCH 22390 (250 pmol) or (-)-sulpiride (250
      pmol). 4. Similarly, penile erection promoted by cocaine (160 micrograms, i.c.)
      was not appreciably affected by i.c. pretreatment with the alpha 1-, alpha 2-, or
      beta-adrenoceptor antagonist, prazosin (50 pmol), yohimbine (50 pmol) or
      propranolol (5 nmol). 5. Whereas lignocaine (4 mumol, i.c.) depressed penile
      erection induced by papaverine (400 micrograms, i.c.), local application of
      cocaine (160 micrograms) into the corpus cavernosum still elicited significant
      elevation in ICP in the presence of lignocaine or papaverine. 6. The increase in
      ICP induced by cocaine (160 micrograms, i.c.) was attenuated dose-dependently by
      prior cavernosal administration of the NO synthase inhibitor, N omega-nitro-L 
      arginine methyl ester (L-NAME, 0.5, 1 or 5 pmol) or NG-monomethyl-L-arginine (L
      NMMA, 2.5, 5 or 10 pmol). The blunting effect of L-NAME or L-NMMA was reversed by
      co-administration of the NO precursor, L-arginine (1 nmol, i.c.). 7. Pretreatment
      by local application into the corpus cavernosum of methylene blue (2.5 mumol), an
      inhibitor of cytosolic guanylyl cyclase, antagonized cocaine-induced penile
      erection. 8. Direct i.c. administration of a NO donor, nitroglycerin (10 or 20
      nmol), mimicked the local action of cocaine by promoting a significant increase
      in ICP. 9. It is concluded that cocaine may induce penile erection by increasing
      ICP via a local action on the corpus cavernosum. This process did not appear to
      involve either dopamine or noradrenaline as the chemical mediator, nor the
      pharmacological action of cocaine as a local anaesthetic. On the other hand, it
      is likely that initiation and maintenance of penile erection elicited by
      cavernosal application of cocaine engaged an active participation of NO and
      subsequent activation of guanylyl cyclase in the corpus cavernosum.

PMID- 8733591
TI  - Second messenger cascade specificity and pharmacological selectivity of the human
      P2Y1-purinoceptor.
AB  - 1. The coding sequence of the P2Y1-purinoceptor was cloned from a human genomic
      library. 2. The open reading frame encodes a protein of 373 amino acids that is
      83% identical to the previously cloned chick and turkey P2Y1-purinoceptor and is
      > or = 95% homologous to the recently cloned rat, mouse, and bovine P2Y1
      purinoceptors. 3. The human P2Y1-purinoceptor was stably expressed in 1321N1
      human astrocytoma cells using a retroviral vector. Although the P2Y1-purinoceptor
      agonist, 2MeSATP, had no effect on inositol phosphate accumulation in cells
      infected with the P2Y1-purinoceptor virus. No effect of 2MeSATP on cyclic AMP
      accumulation was observed in P2Y1-receptor-expressing 1321N1 cells. 4. The
      pharmacological selectively of 18 purinoceptor agonists was established for the
      expressed human P2Y1-purinoceptor. 2MeSATp was more potent than ATP but less
      potent than 2MeSADP. ADP also was more potent than ATP. A similar maximal effect
      was observed with most agonists tested. However, alpha, beta-MeATP had no effect
      and 3'-NH2-3'-deoxyATP and A2P4 were partial agonists. The order of potency of
      agonists for activation of the turkey P2Y1-purinoceptor, also stably expressed in
      1321N1 cells, was identical to that observed for the human P2Y1-purinoceptor. 5.
      C6 glioma cells express a P2Y-purinoceptor that inhibits adenylyl cyclase but
      does not activate phospholipase C. Expression of the human P2Y1-purinoceptor in
      C6 cells conferred 2MeSATP-stimulated inositol lipid hydrolysis to these cells.
      The phospholipase C-activating human P2Y1-purinoceptor could be delineated from
      the endogenous P2Y-purinoceptor of C6 glioma cells by use of the P2-purinoceptor
      antagonist, PPADS, which blocks the P2Y1-purinoceptor but does not block the
      endogenous P2Y-purinoceptor of C6 cells. P2-purinoceptor agonists also exhibited
      differential selectivities for activation of these two P2Y-purinoceptors.

PMID- 8733592
TI  - Species specificity in the blood cholesterol-lowering effect of YM-16638.
AB  - 1. The compound YM-16638, [[5-[[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl]
      thio]-1,3,4-thiadiazol-2-yl]thio] acetic acid was developed in a series of in
      vitro and in vivo studies as a leukotriene D4 receptor antagonist. 2. In a
      clinical trial as a leukotriene antagonist drug, this compound was found to have
      a potent serum cholesterol lowering effect in normolipidaemic healthy male
      volunteers. 3. In the present study, we investigated the serum cholesterol lower
      effect of this compound in various species of experimental animals. 4.
      Administration of YM-16638 did not cause a significant decrease in serum total
      cholesterol (TC) in mice (up to 200 mg kg-1, body weight per day for 28 days),
      rats (200 mg kg-1 for 15 days) or rabbits (90 mg kg-1 for 18 days). In hamsters,
      administration of YM-16638 orally or by peritoneal injection at 50 mg kg-1 or
      more daily for 7 days caused a significant decrease in serum TC and the rate of
      body weight gain. In monkeys, serum TC did not change in YM-16638-administered
      squirrel monkeys (50 mg kg-1 daily for 3 weeks), but a significant decrease in
      serum TC was observed in cynomolgus monkeys (33% decrease at 30 mg kg-1 for 4
      weeks) and rhesus monkeys (27% decrease at 30 mg kg-1 for 3 weeks) without any
      serious decrease in body weight. These results were consistent with those in a
      phase I study with human subjects. In contrast, serum alanine aminotransferase
      (ALT) level decreased in all animals after YM-16638 treatment. 5. From these
      results, we conclude that YM-16638 has a potent hypocholesterolaemic effect, but
      that this effect if species-specific and is only recognized clearly in human
      subjects and old-world monkeys.

PMID- 8733593
TI  - Nitric oxide synthase-cyclo-oxygenase pathways in organum vasculosum laminae
      terminalis: possible role in pyrogenic fever in rabbits.
AB  - 1. Fever was induced in rabbits by administration of Escherichia coli endotoxin
      (lipopolysaccharide; LPS; 0.001-10 micrograms) into the organum vasculosum
      laminae terminalis (OVLT). Deep body temperature was evaluated over a period of 7
      h. 2. The LPS-induced febrile response was mimicked by intra-OVLT injection of
      the nitric oxide (NO) donors, S-nitroso-acetylpenicillamine (SNAP, 1-10
      micrograms), sodium nitroprusside (SNP, 50 micrograms), or hydroxylamine (10
      micrograms), the cyclic GMP analogue 8-bromo-cyclic GMP (8-Br-cyclic GMP, 10-100
      micrograms), or prostaglandin E2 (PGE2, 0.2 micrograms). 3. Dexamethasone (Dex, a
      potent inhibitor of the transcription of inducible NO synthase, iNOS, 10
      micrograms), anisomycin (a protein synthesis inhibitor, 100 micrograms), L-N5-(1
      iminoethyl)ornithine (L-NIO; an irreversible NOS inhibitor, 10-200 micrograms),
      aminoguanidine (a specific iNOS inhibitor, 1000 micrograms), or NG-methyl-L
      arginine acetate (L-NMMA, a NOS inhibitor, 100 micrograms) inhibited fever
      induced by LPS when injected into the OVLT 1 h before LPS injection. An intra
      OVLT dose of 1000 micrograms of NG-nitro-L-arginine methyl ester (L-NAME, a
      potent inhibitor of constitutive NOS) did not exhibit antipyretic effects. 4.
      Methylene blue (an inhibitor of NOS and soluble guanylate cyclase, 1-10
      micrograms), 6-(phenylamino)-5,8-quinolinedione (LY-83583; an inhibitor of
      soluble guanylate cyclase and NO release, 20 micrograms), or indomethacin (an
      inhibitor of cyclo-oxygenase, COX, 400 micrograms) inhibited fever induced by LPS
      when injected into the OVLT 1 h before LPS injection. Pretreatment with methylene
      blue or haemoglobin (a NO scavenger, 100 micrograms) attenuated the fever induced
      by intra-OVLT injection of SNAP. 5. The PGE2-induced fever was potentiated,
      rather then attenuated, by pretreatment with an intra-OVLT dose of animoguanidine
      (1000 micrograms), L-NMMA (100 micrograms) or L-NIO (200 micrograms). 6. These
      results suggest that iNOS-COX pathways in the OVLT represent an important
      mechanism for modulation of pyrogenic fever in rabbits.

PMID- 8733594
TI  - Deficient nitric oxide responsible for reduced nerve blood flow in diabetic rats:
      effects of L-NAME, L-arginine, sodium nitroprusside and evening primrose oil.
AB  - 1. This study examined the potential role of impaired nitric oxide production and
      response in the development of endoneurial ischaemia in experimental diabetes.
      Rats were anaesthetized (Na pentobarbitone 45 mg kg-1, diazepam 2 mg kg-1) for
      measurement of sciatic nerve laser Doppler flux and systemic arterial pressure.
      Drugs were administered into the sciatic endoneurium via a microinjector attached
      to a glass micropipette. 2. In two separate studies comparing diabetic rats
      (streptozotocin-induced; 8-10 wk duration) with controls, nerve Doppler flux in
      diabetic rats (Study 1, 116.6 +/- 40.4 and Study 2, 90.1 +/- 34.7 (s.d.) in
      arbitrary units) was about half that measured in controls (219.6 +/- 52.4 and
      212.8 +/- 95.5 respectively; P < 0.005 for both). There were no significant
      differences between the two in systemic arterial pressure. 3. Inhibition of
      nitric oxide production by microinjection of 1 nmol L-NAME into the endoneurium
      halved flux in controls (to 126.3 +/- 41.3 in Study 1 and 102.1 +/- 38.9 in Study
      2; both P < 0.001), with no significant effect in diabetic rats, indicating
      markedly diminished tonic nitric oxide production in the latter. D-NAME was
      without effect on nerve Doppler flux. 4. L-Arginine (100 nmol), injected after L
      NAME, markedly increased flux in controls (by 65.8% (P < 0.03) and 97.8% (P <
      0.01) in the two studies) and by proportionally similar amounts in diabetic rats
      [75.8% (P < 0.001) and 60.2% (P < 0.02)]. The nitro-donor, sodium nitroprusside
      (SNP; 10 nmol) had similar effects to L-arginine in both groups (increases of
      66.0% in controls and 77.5% in diabetics; both P < 0.002). 5. A second diabetic
      group, treated with evening primrose oil performed exactly like control rats in
      respect of responses to L-NAME, L-arginine and SNP. 6. These findings implicate
      deficient nitric oxide in nerve ischaemia of diabetes and suggest correction
      thereof as a mechanism of action of evening primrose oil.

PMID- 8733595
TI  - Endothelin-1-induced potentiation of human airway smooth muscle proliferation: an
      ETA receptor-mediated phenomenon.
AB  - 1. In this study the mitogenic effects in human cultured tracheal smooth muscle
      cells of endothelin-1 (ET-1), ET-3, and sarafotoxin S6c (S6c), the ETB receptor
      selective agonist, were explored either alone or in combination with the potent
      mitogen, epidermal growth factor (EGF). 2. In confluent, growth-arrested human
      airway smooth, neither ET-1 (0.01 nM-1 microM) nor ET-3 (0.001 nM-1 microM) or
      S6c (0.01 nM-1 microM) induced cell proliferation, as assessed by [3H]-thymidine
      incorporation. In contrast, EGF (1.6 pM-16 nM) produced concentration-dependent
      stimulation of DNA synthesis (EC50 of about 0.06 nM). The maximum increase of
      about 60 fold above control, elicited by 16 nM EGF, was similar to that obtained
      with 10% foetal bovine serum (FBS). EGF (0.16-16 nM) also produced a
      concentration-dependent increase in cell counts, whereas ET-1 (1-100 nM) was
      without effect on this index of mitogenesis. 3. ET-1 (1-100 nM) potentiated EGF
      induced proliferation of human tracheal smooth muscle cells. For example, ET-1
      (100 nM), which alone was without significant effect, increased by 3.0 to 3.5
      fold the mitogenic influence of EGF (0.16 nM). The potentiating effect of ET-1 on
      EGF-induced proliferation was antagonized by BQ-123 (3 microM), the ETA receptor
      antagonist, but was unaffected by the ETB receptor antagonist BQ-788 (10 microM).
      4. Neither ET-3 (1-100 nM) nor S6c (1-100 nM) influenced the mitogenic effects of
      EGF (0.16-1.6 nM). 5. [125I]-ET-1 binding studies revealed that on average the
      ratio of ETA to ETB receptors in human cultured tracheal smooth muscle cells was
      35:65 ( +/- 3; n = 4), confirming the predominance of the ETB receptor subtype in
      human airway smooth muscle. 6. These data indicate that ET-1 alone does not
      induce significant human airway smooth muscle cell proliferation. However, it
      potently potentiated mitogenesis induced by EGF, apparently via an ETA receptor
      mediated mechanism. These findings suggest that ET-1, a mediator detected in
      increased amounts in patients with acute asthma, may potentiate the proliferative
      effects of mitogens and contribute to the airway smooth muscle hyperplasia
      associated with chronic severe asthma.

PMID- 8733596
TI  - Effects of the endothelin receptor antagonist, SB 209670, on circulatory failure
      and organ injury in endotoxic shock in the anaesthetized rat.
AB  - 1. This study investigates the effects of the non-selective ETA/ETB receptor
      antagonist, SB 209670, on systemic haemodynamics, renal function, liver function,
      acid-base balance and survival in a rat model of endotoxic shock. 2. Injection of
      E. coli lipopolysaccharide (LPS, 10 mg kg-1, i.v.) resulted in increases in the
      serum levels of tumour necrosis factor-alpha (TNF-alpha, maximum 60 min after
      LPS), endothelin-1, (ET-1; maximum 120 min after LPS), and interferon-gamma (IFN
      gamma, maximum 180 min after LPS). 3. Injection of LPS also resulted in a fall in
      blood pressure from 113 +/- 3 mmHg (time = 0) to 84 +/- 4 mmHg at 360 min (n =
      15) as well as a hyporeactivity to the vasoconstrictor responses elicited by
      noradrenaline (NA, 1 microgram kg-1, i.v.). Pretreatment of rats with a
      continuous infusion of SB 209670 (3 mg kg-1, i.v. bolus + 100 micrograms kg-1,
      i.v. infusion commencing 15 min prior to LPS) significantly augmented the
      hypotension as well as the vascular hyporeactivity to NA caused by endotoxaemia.
      4. Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus given 15 min
      prior to LPS) or infusion of SB 209670 (bolus dose and infusion as above)
      resulted in a reduction in 6 h-survival from 71% (control) to 30% and 13%,
      respectively. 5. Endotoxaemia for 4 h resulted in rises in the serum levels of
      urea and creatinine (indicators of renal failure), but not in the serum levels of
      bilirubin, GPT and GOT (indicators of liver dysfunction and/or hepatocellular
      injury). Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus 15 min
      prior to LPS) significantly augmented the serum levels of creatinine, bilirubin,
      GPT and GOT caused by endotoxin. In addition, endotoxaemia caused, within 15 min,
      an acute metabolic acidosis (falls in pH, HCO3- and base excess) which was
      compensated by hyperventilation (fall in PaCO2). Pretreatment of LPS-rats with SB
      209670 (3 mg kg-1, i.v. bolus) significantly augmented the metabolic acidosis
      caused by LPS. 6. Thus, the non-selective ETA/ETB receptor antagonist, SB 209670,
      augments the degree of (i) hypotension, (ii) vascular hyporeactivity to
      noradrenaline, (iii) renal dysfunction and (iv) metabolic acidosis caused by
      endotoxin in the anaesthetized rat. In contrast to rats treated with LPS alone,
      LPS-rats treated with SB 209670 exhibited liver dysfunction and hepatocellular
      injury. We propose that the release of endogenous ET-1 serves to maintain blood
      pressure and subsequently organ perfusion in septic shock.

PMID- 8733597
TI  - International collaborative study by in vitro bioassays and immunoassays of the
      First International Standard for Inhibin, Human Recombinant.
AB  - The First International Standard for Inhibin, Human Recombinant, (ISI), a
      lyophilized preparation of rDNA-derived human 32 kDa Inhibin A in ampoules coded
      91/624, was evaluated by international collaborative study for its suitability to
      serve as an International Standard. This study, which involved 15 laboratories in
      nine countries, included a variety of in vitro bioassays and immunoassays. The
      ISI was compared with two other lyophilized preparations of human recombinant
      inhibin, the International Standard for Porcine inhibin (ISP) and preparations of
      human follicular fluid inhibin. Predicted loss of activity based on estimates of
      potency of contents of ampoules which had been stored under conditions of
      accelerated thermal degradation indicated that the ISI has satisfactory
      stability. On the basis of the results of this study, the ISI was deemed suitable
      to serve as a standard for in vitro bioassays and immunoassays and was
      established by the Expert Committee on Biological Standardization of the World
      Health Organization as the First International Standard for inhibin, recombinant
      human, with an assigned unitage of 150,000 International Units per ampoule. This
      unitage maintains an approximate continuity of units with the ISP.

PMID- 8733598
TI  - The affinity of binding of digoxin to ovine anti-digoxin Fab (DIGIBIND)
      preparations.
AB  - A fundamental study was performed to assess the binding characteristics of an
      ovine anti-digoxin-Fab preparations, DIGIBIND, for digoxin, using equilibrium
      dialysis. The average mass of the antibody fragment was determined by matrix
      assisted laser-desorption mass spectrometry to be 46,200 Da. The main conclusions
      are that the binding affinity and capacity are similar for several batches,
      produced over a period of several years. The average median affinity for digoxin
      of five batches determined by Sips analysis was 3.4 x 10(11) M-1 (range 1.95-6.15
      x 10(11) M-1) (corresponding to dissociation constants, Kd, in the range 1.63
      5.13 pM), and the index of heterogeneity was 0.78 +/- 0.03.

PMID- 8733599
TI  - Novel assays based on human growth hormone receptor as alternatives to the rat
      weight gain bioassay for recombinant human growth hormone.
AB  - Two methods, High-Performance Receptor Binding Chromatography (HPRBC) and Cell
      Proliferation (CP), have been developed as alternatives to the classical
      hypophysectomized rat weight gain bioassay for the determination of potency for
      recombinant human growth hormone (rhGH). In the HPRBC assay, rhGH is combined
      with an excess of the soluble extracellular domain of the recombinant human
      growth hormone receptor (referred to as 'receptor' in the discussion of the HPRBC
      assay). Nondenaturing size-exclusion chromatography is used to analyzed the
      resulting complex, which forms in a 2:1 receptor to rhGH ratio. The 2:1 complex
      is assayed at a concentration near the Kd (approximately 0.4 nM), providing high
      specificity for rhGH and detection of rhGH variants with reduced activity. In the
      CP assay, a mouse myeloid leukaemia cell line (FDC-P1) transfected with the full
      length receptor is exposed to varying levels of rhGH for 16-20 h. The
      incorporation of 3H-thymidine into DNA is used as an index of cell proliferation.
      The results show that the HPRBC assay provides significantly improved precision
      with a relative standard deviation (RSD) of < or = 5% vs. an RSD of 23% for the
      rat bioassay. The CP assay has RSDs of 4-16%. Analysis of rhGH variants and
      mutants shows that the potencies measured by both the HPRBC and CP assays are in
      general agreement with the rat weight gain bioassay. Both of the HPRBC and CP
      assays are sufficiently rugged for operating in a Good Manufacturing Practices
      (GMP) routine batch release testing environment. In vitro alternatives such as
      the HPRBC and CP assays build a foundation for replacing the hypophysectomized
      rat weight gain bioassay by correlating receptor dimerization, binding
      specificity and signal transduction with the biological activity of rhGH.

PMID- 8733600
TI  - An enzyme immunoassay based micro-neutralization test for titration of antibodies
      to human cytomegalovirus (CMV) and its correlation with direct ELISA measuring
      CMV IgG antibodies.
AB  - An ELISA-based micro-neutralization (Nt) test in MRC-5 cells for titration of
      neutralizing antibodies against human cytomegalovirus (CMV) in human plasma and
      preparations of immune globulins was developed to eliminate microscopic reading
      of cytopathic effect (CPE), a process that is subjective and time consuming. Un
      neutralized CMV from the Nt reaction and grown in MRC-5 cells as per the standard
      micro-Nt test was coated in the same plates by various methods and CMV antigen
      was quantified by polyclonal or monoclonal CMV antibodies. Optimal coating of
      plates with CMV antigen (100 TCID50 of virus grown on MRC-5 cells for 7 days) was
      obtained by freezing/thawing of virus infected MRC-5 cells in phosphate buffered
      saline, ph 7.2. The CMV antigen treated sequentially with CMV monoclonal antibody
      to late nuclear protein antigen, goat anti-mouse IgG3 alkaline phosphatase
      conjugate and phosphatase substrate gave an absorbance of 1 at 410 nm wavelength
      whereas uninfected MRC-5 cells treated under similar conditions did not show any
      absorbance. The optimal Nt reaction occurred at 37 degrees C for 1-2 h and was
      unaffected by complement. At 4 degrees C, CMV was inactivated in 1-2 h. The
      antibody titres were affected by the virus dose used in the Nt test over a range
      of 20 to 798 TCID50. When the titre was determined against a reference serum, the
      effect of virus dose on the Nt titre was reduced. Complete neutralization virus
      read microscopically correlated with ELISA absorbance of < 0.1. CPE produced by
      approximately 1 TCID50 of CMV showed an absorbance of 0.1 or more. The
      correlation coefficient (r) between Nt titres and CMV IgG antibodies determined
      by ELISA was 0.69 (P < 0.001) for 257 human plasma samples and 0.85 (P < 0.001)
      for 50 immune globulin preparations.

PMID- 8733601
TI  - Evaluation of current sterility tests for human live viral vaccines.
AB  - Current sterility tests for human viral vaccines were evaluated. A total of 43
      lots of bulk suspension of live viral vaccines (measles, mumps, rubella and oral
      poliomyelitis) produced by six manufacturers in Japan were evaluated for
      bacteriostatic and mycoplasmastatic activities. Some of them showed fairly high
      bacteriostatic and mycoplasmastatic activities, due to antibiotics added during
      vaccine production. It was concluded that the current sterility test for
      mycoplasmas is not reliable to detect viable mycoplasmas in live viral vaccines.

PMID- 8733602
TI  - Estimation of antigenic tetanus toxoid extracted from biodegradable microspheres.
AB  - Microspheres made from poly (lactic/glycolic acid) polymers have been considered
      as a new delivery system for single-dose tetanus toxoid (TT) vaccines. One of the
      most critical properties of the proposed vaccines is the loading and distribution
      of TT as this will have a profound effect on immunogenicity. As the concentration
      of TT in microspheres is very low sensitive assay methods are required. An assay
      incorporating monoclonal antibody (MAb) recognizing a neutralizing epitope and
      cross-reacting with TT was developed (MAp capture ELISA) which provided a
      sensitivity of 0.001 Lf/ml. An extraction procedure was devised which did not
      destroy the antigenicity and gave a recovery of 90.6 +/- 3.39% when applied to
      different preparations. The extracted TT was then quantified by MAb capture ELISA
      which was estimated to be 250-fold more sensitive than single-site ELISA for
      toxoid. The loading of 20 microspheres preparations (12 filled and 8 placebo) was
      determined by both protein micro-BCA assay and the developed assay for TT. The TT
      content obtained for the 12 filled microspheres preparations from different
      sources varied up to 400-fold (range 0.01-4.0 Lf/mg microspheres). The utility of
      the MAb capture ELISA for detection of total antigenic content in microspheres
      was confirmed by the observation that the determine TT loading correlated with
      the theoretical loading predicted from the protein content for the best
      preparations. Preparations with high loading gave the greatest peak response.
      There was no relationship between dose and the in vivo immunogenic response,
      suggesting that encapsulated vaccines with differential loading, release
      properties and presence of excipients will have different response curves in
      vivo. Hence, the present assay, when combined with information on toxoid release
      rate and presence and effect of excipients may be of value in predicting in vivo
      response.

PMID- 8733603
TI  - A quantitative method for the determination of plasmid copy number in recombinant
      yeast.
AB  - A method is described for the determination of plasmid copy number (PCN) in the
      recombinant yeast Saccharomyces cerevisiae producing human coagulation Factor
      XIII. Southern hybridization of restriction endonuclease HindIII-digested total
      DNA from yeast transformant with the 32P-labelled URA3 gene as a probe detected
      two band: one corresponding to the chromosomal URA3 gene and the other
      corresponding to the recombinant plasmid. Thus, the present method using the
      genomic URA3 gene as an internal standard allowed an estimation of both the
      plasmid and the standard simultaneously. Since haploid yeast cells harbour one
      copy of genomic URA3 gene, the PCN can be determined as the ratio of the amount
      of plasmid to that of genomic URA3 gene. A linear relationship between the
      determined PCN and the plasmid content was observed ranging from 0.3 to 200 ng.
      The method is reproducible and independent of the extraction efficiency for the
      recombinant plasmid. The present method was successfully used to analyzed the PCN
      of a centromere-based plasmid YCp50 (= 2.7) and of a 2 microns-based plasmid
      pEMBLyex4 (= 112).

PMID- 8733604
TI  - Use of a diluent containing protein for dilution of potent toxins like tetanus
      toxin for in vivo tests.

PMID- 8733605
TI  - (Z,E)-alpha-farnesene--an electroantennogram-active component of Maladera matrida
      volatiles.
AB  - It has previously been shown in field-trapping experiments and laboratory
      olfactometer bioassays that virgin females of Maladera matrida Argaman
      (Coleoptera, Scarabaeidae) and their volatiles, both in the presence of food (cut
      peanut leaves), are efficient attractants for M. matrida males and females. In
      this study GC-EAD experiments using male antennae and GC-MS experiments revealed
      that (Z,E)-alpha-farnesene is an active component of M. matrida female volatiles.
      The identification and quantitive electrophysiological responses (EAG) of
      synthetic (Z,E)-alpha-farnesene were obtained with male and female antennae. It
      was also shown that (Z,E)-alpha-farnesene is not a component of the plant
      volatiles that serve as synergistic components of the mixture of attractants or
      of the source of food for M. matrida.

PMID- 8733606
TI  - Chemical ecology of astigmatid mites--XLV. (2R, 3R)-epoxyneral: sex pheromone of
      the acarid mite Caloglyphus sp. (Acarina: Acaridae).
AB  - (2R,3R)-2,3-Epoxy-3,7-dimethyl-6-octenal [(2R,3R)-epoxyneral] was identified as
      the female sex pheromone from an acarid mite, Caloglyphus sp.
      (Astigmata:Acaridae), whose phoretic hypopi had been collected from the
      Cockchafer, Melolontha japonica (Coleoptera: Scarabaeidae). Sexual activity of
      the males was induced by exposure to a 0.1-1 ng dose of synthetic (2R,3R)
      epoxyneral. The enantiomer of the pheromone, (2S,3S)-epoxyneral, was inactive and
      its admixture did not inhibit the activity of the natural pheromone.

PMID- 8733607
TI  - Assignment of absolute stereochemistry to an insect pheromone by chiral
      amplification.
AB  - Chiral amplification, a new strategy for determining the absolute configuration
      of difficulty available natural secondary alcohols or analogous amines, is
      described. Using this technique, the R configuration can be assigned to both
      components of the male sex pheromone emitted by the longhorn beetle, Anaglyptus
      subfasciatus. The application of this approach to fourteen alcohols and four
      amines illustrates its scope and limitations.

PMID- 8733608
TI  - (3E,8Z,11Z)-3,8,11-tetradecatrienyl acetate, major sex pheromone component of the
      tomato pest Scrobipalpuloides absoluta (Lepidoptera: Gelechiidae).
AB  - The major sex attractant emitted by Scrobipalpuloides absoluta females is shown
      to be (3E,8Z,11Z)-3,8,11-tetradecatrien-1-yl acetate by a novel strategy
      involving the random reduction of double bonds, followed by methylthiolation of
      the reduced products. Each female sex gland contains ca. 1-5 ng of this
      pheromone. This triene ester, synthesized by a stereospecific procedure, shows
      spectral and gas chromatographic properties identical to those of the natural
      substance. In field tests and wind tunnel bioassays, the synthetic ester was
      found to be highly attractive to conspecific males. The male response to this
      pheromone, however, is restricted to the same early-morning time window during
      which females exhibit calling behavior.

PMID- 8733609
TI  - (R-Z)-7,15-hexadecadien-4-olide, sex pheromone of the yellowish elongate chafer,
      Heptophylla picea.
AB  - An active component of the sex pheromone system of the yellowish elongate chafer,
      Heptophylla picea was identified by GC-EAD. Mass spectral data and hydrogenation
      revealed that the active compound was a hexadecadien-4-olide. It was not possible
      to determine the double bond positions by direct DMDS derivatization of the
      pheromone, but partial hydrogenation (diimide) followed by DMDS derivatization
      showed that the double bonds were located in positions 7 and 15. FTIR (tracer) of
      the pheromone corroborated the lactone structure (1772 cm-1) and showed a band
      characteristic of a terminal double bond at 3073 cm-1, and one of a double bond
      in the cis-configuration at 3002 cm-1. Chiral resolution of the pheromone, after
      hydrogenation, demonstrated that the natural lactone had the (R)-stereochemistry.
      Synthetic (R,Z)-7,15-hexadecadien-4-olide, prepared from L-malic acid in 14
      steps, was identical to the natural product in MS, IR, retention times and
      biological activity. This is the first fatty acid derivative compound found as a
      sex pheromone of a Melolonthinae species and as far as biosynthesis is concerned
      this is the most complex pheromone constituent of a scarab species.

PMID- 8733610
TI  - Chemical identification, electrophysiological and behavioral activities of the
      pheromone of Metamasius hemipterus (Coleoptera: Curculionidae).
AB  - Five hydroxylated aliphatic molecules were identified as the pheromone produced
      by male West Indian Sugarcane Borer (WISB): 4-methyl-5-nonanol (1), 2-methyl-4
      heptanol (2), 2-methyl-4-octanol (3), 5-nonanol (4) and 3-hydroxy-4-methyl-5
      nonanone (5). Electroantennographic recordings revealed antennal responses to
      compounds 1, 2, 3 and 4. Significant EAGs were also recorded in response to
      pheromone compounds of weevils belonging to the same subfamily and structurally
      related to the WISB pheromone. The natural pheromone elicited aggregation
      behavior on WISB adults in laboratory bioassays.

PMID- 8733611
TI  - Sex attractant pheromone of the pecan nut casebearer (Lepidoptera: Pyralidae).
AB  - A female-produced sex pheromone for the pecan nut casebearer, Acrobasis
      nuxvorella Neunzig, has been identified from pheromone gland extracts of calling
      female moths. The compound (9E,11Z)-hexadecadienal [(9E,11Z)-16:Ald] was
      identified by coupled GC-EAD and retention time matches with a synthetic standard
      on four capillary GC columns of different polarities. Corroboration of the
      identification of (9E,11Z)-16:Ald by other analytical chemistry methods was not
      possible due to the minute quantities of pheromone extracted (< 1
      picogram/female). In field studies, gray rubber septa impregnated with 100
      micrograms of synthetic (9E,11Z)-16:Ald were attractive to male moths, whereas
      higher and lower doses were less attractive. The homologous (9E,11Z)-15:Ald was
      also slightly attractive while the more highly conjugated analogues, (9E,11Z,13Z)
      and (9E,11Z,13E)-16:Ald, were not.

PMID- 8733612
TI  - The pheromone system of the male danaine butterfly, Idea leuconoe.
AB  - Male Idea leuconoe butterflies release a complex mixture of volatiles from their
      pheromone glands (hairpencils) during courtship. The pheromone components geranyl
      methyl thioether (2), viridifloric beta-lactone (3) and 6-hydroxy-4-dodecanolide
      (10) have been synthesized for the first time. Therefore, the structural
      assignment of these new natural products could be proved. Related 7-hydroxy-5
      alkanoides are also present in the extract. The volatiles are embedded in a
      lipidic, matrix with more than 150 components. This matrix consists of alkanes,
      alkenes, 2,5-dialkyltetrahydrofurans, secondary alkanols and alkenols as well as
      alkanones and alkenones. Several regioisomers of the oxidized hydrocarbons occur.
      The elucidation of double bond positions has been performed by MS using DMDS
      adducts.

PMID- 8733613
TI  - The aphid sex pheromone cyclopentanoids: synthesis in the elucidation of
      structure and biosynthetic pathways.
AB  - Identification of a range of aphid sex pheromones as comprising the
      cyclopentanoids (4aS,7S,7aR)-nepetalactone, (1R,4aS,7S,7aR)-nepetalactol and the
      (1S)- and (1R,4aR,7S,7aS)-nepetalactols required samples authenticated by 1H and
      13C NMR. These and related compounds were provided by small scale synthesis and
      extraction from plants in the genus Nepeta (Lamiaceae). The subsequent discovery
      that the synthetic sex pheromones could attract males, and also parasitic wasps
      that attack aphids, has created a need for large scale syntheses of the
      cyclopentanoids. This is afforded by cyclisation of the 8-oxo-1-enamine of
      citronellal as originally developed by Schreiber and co-workers (1986).
      Investigation into the biosynthesis of the cyclopentanoids by plants for
      exploiting aphid sex pheromones in crop protection by means of molecular biology
      required synthesis of putative biosynthetic intermediates, some with radioactive
      isotopic labelling, particularly 8-oxidised monoterpene alcohols and aldehydes.

PMID- 8733614
TI  - Identification and synthesis of new bicyclic acetals from the mountain pine
      beetle, Dendroctonus ponderosae Hopkins (Col.: Scol.).
AB  - Head-space volatiles obtained from male mountain pine beetles, Dendroctonus
      ponderosae, were analyzed by coupled GC-MS and chiral gas chromatography. 5-Ethyl
      7-methyl-6,8-dioxabicyclo[3.2.1]octane (6) was found as a new naturally occurring
      isomer of brevicomin (1). In addition, several stereoisomers of 7-ethyl-5-methyl
      6,8-dioxabicyclo[3.2.1]octan-2-ol (11) and 1-(5-methyl-6,8
      dioxabicyclo[3.2.1]octyl)ethanol (12) could be identified. Relative and absolute
      configurations of the compounds were determined by unambiguous syntheses, which
      are described.

PMID- 8733615
TI  - Enzymatic synthesis of (2E,4E)-(6R,10R)-4,6,10,12-tetramethyl-2,4-tridecadien-7
      one, the sex pheromone of Matsucoccus matsumurae Japanese pine bast scale.
AB  - The sex pheromone of Matsucoccus matsumurae Japanese pine bast scale (2E,4E)
      (6R,10R)-4,6,10,12-tetramethyl-2,4-tridecadien-7-one (1) was synthesized with
      stereocontrol from (2R,4S)-5-acetoxy-2,4-dimethyl-pentanol (3), which in turn was
      prepared by lipase-catalyzed transesterification of meso-2,4-dimethyl-1,5
      propanediol (2).

PMID- 8733616
TI  - Pheromone syntheses: a tropical approach. Enantioselective synthesis of the
      (2R,6S,10S) and (2S,6S,10S) isomers of methyl 2,6,10-trimethyldodecanoate.
AB  - The enantioselective syntheses of two stereoisomers, (2R,6S,10S) and (2S,6S,10S),
      of methyl 2,6,10-trimethyldodecanote, out of eight possible isomers, are
      described , employing the stereoselective hydroboration of (-)-isopulegol (2) and
      (+)-neo-isopulegol (2a) as the key reaction.

PMID- 8733617
TI  - A versatile and convenient protocol for the stereocontrolled synthesis of
      olefinic insect pheromones.
AB  - A combination of the Horner-Emmons synthesis of alkyl 2,4-dienoates with their
      hydrogenation over complex L.Cr(CO)3 catalysts (L = 3CO or arene) provides a
      versatile, stereocontrolled and operationally simple approach to the (Z)
      disubstituted, (Z)-trisubstituted, (E)-trisubstituted alkenes and skipped (Z,Z)
      disubstituted diolefins with a homoallylic type of functionally. This protocol,
      sometimes supplemented by an enzymatic hydrolysis, was successfully applied to
      the synthesis of configurationally pure (gp > or = 98%) pheromones of the
      furniture carpet beetle, dry bean beetle, rusty grain beetle, square-necked grain
      beetle and a trail-following pheromone mimic for subterranean termites.

PMID- 8733618
TI  - Synthesis of some analogues of blattellastanoside A, the steroidal aggregation
      pheromone of the German cockroach.
AB  - Blattellastanoside A, the aggregation pheromone of the German cockroach, is a
      chlorinated steroid glucoside with the 5 beta-stigmastane skeleton. Its analogues
      were synthesized in order to clarify the structure-activity relationship. They
      are 1a with the 5 beta-cholestane skeleton, 1b with the 5 beta-androstane
      skeleton, 1c with a fluorine substituent instead of the chlorine and 1d with a
      beta-D-galactopyranose instead of the beta-D-glucopyranose of the original
      pheromone. Their bioassay shows that 1a and 1c are active, while 1b and 1d are
      totally devoid of pheromone activity. The aglycone of blattellastanosides A and B
      were active.

PMID- 8733620
TI  - On the regioselectivity of the Baeyer-Villiger reaction of 2,6-dialkyl
      cyclohexanones: application to the synthesis of sordidin, a male pheromone
      emitted by Cosmopolites sordidus.

PMID- 8733619
TI  - Enzymatic preparation of (4R,6R)-4-hydroxy-1,7-dioxaspiro[5.5]undecane and its
      antipode, the minor component of the olive fruit fly pheromone.

PMID- 8733621
TI  - A convenient synthesis of trans-sabinene hydrate from (-)-3-thujol via a highly
      selective ene reaction of singlet oxygen.

PMID- 8733622
TI  - Asymmetric aldol condensation as a route to polypropionate derived pheromones.
AB  - The synthesis of the polypropionate-derived pheromones sitophilate (1) and
      sitophilure (2) are described using an asymmetric aldol condensation as the key
      step to adduct 6; compound 6 was smoothly converted to the antipodes of each
      pheromone. This procedure can be expanded to more complicated structures with the
      same type of syn configuration such as stegobinone (3) and serricornin (4).

PMID- 8733623
TI  - Polyketide origin of pheromones of Carpophilus davidsoni and C. mutilatus
      (Coleoptera: Nitidulidae).
AB  - Biosynthesis of pheromones from Carpophilus davidsoni Dobson and C. mutilatus
      Erichson was investigated by feeding the beetles diets containing isotopically
      substituted (13C and deuterium) fatty acids and then analyzing the resulting
      labeled pheromone components. (2E,4E,6E,8E)-7-Ethyl-3,5-dimethyl-2,4,6,8-undecate
      traene, (2E,4E,6E,8E)-3,5,7-trimethyl-2,4,6,8-undecatetraen e and (2E,4E,6E)-5
      ethyl-3-methyl-2,4,6-nonatriene from C. davidsoni and (3E,5E,7E)-5-ethyl-7-methyl
      3,5,7-undecatriene from C. mutilatus were abundant enough to be analyzed by both
      NMR spectroscopy and MS. Eleven additional minor analogues were analyzed only by
      MS. Each hydrocarbon can be assembled from just three different acyl units: The
      initial unit can be acetate, propionate or butyrate. Propionate is the second
      unit in all of the analogues encountered so far, extending the chain by two
      carbons and producing a methyl branch. Subsequent chain-extending units can be
      either propionate or butyrate, leading to additional methyl or ethyl branches,
      respectively. The final acyl unit is either propionate or butyrate and it loses
      its carboxyl carbon during hydrocarbon biosynthesis. A hydrocarbon with four
      total units is a triene and one with five is a tetraene. Assembly is proposed to
      be as in usual fatty acid anabolism, except that other precursor units are used
      in addition to acetate and that the double-bond reduction step of each chain
      elongation cycle does not occur, leaving the conjugated, unsaturated system.
      Seven of the analyzed hydrocarbons were not previously known to occur in C.
      davidsoni; two of these are novel: (2E,4E,6E,8E)-5,7-diethyl-3-methyl-2,4,6,8
      undecate traene and (2E,4E,6E)-3,5-dimethyl-2,4,6-octatriene.

PMID- 8733624
TI  - Synthesis of [14,14,14-2H3] 12-hydroxytetradecanoic acid and [13,14-2H2] 11
      hydroxytetradecanoic acid useful as tracers to study a (11E)-desaturation
      reaction in Spodoptera littoralis.
AB  - The synthesis of deuterium labeled 11- and 12-hydroxytetradecanoic acids to study
      a (11E) desaturase in the moth Spodoptera littoralis is reported. [14,14,14-2H3]
      12-hydroxytetradecanoic acid was synthesized in four steps from 11-iodo-1
      undecene in 49% overall yield. Deuterium was introduced by reaction of an epoxy
      ester with (CD3)2CuLi. The preparation of [13,14-2H2] 11-hydroxytetradecanoic
      acid was carried out in six steps from 11-bromoundecanoic acid in 55% overall
      yield. In this case, label was introduced by deuteration of an homoallyl alcohol
      with D2, using the Wilkinson catalyst. Incubation of pheromone glands with either
      of both acids did not lead to the formation of the labeled (11E)-tetradecenoic
      acid.

PMID- 8733625
TI  - Transformation of presumptive precursors to frontalin and exo-brevicomin by bark
      beetles and west Indian sugarcane weevil (Coleoptera).
AB  - (Z)-6-Nonen-2-one (1) has recently been shown to be the biosynthetic precursor
      for the aggregation pheromone exo-brevicomin (2) in mountain pine beetle (MPB)
      males, Dendroctonus ponderosae (Hopkins). We tested the hypotheses that (1) 6
      methyl-6-hepten-2-one (3) is the biosynthetic precursor for the aggregation
      pheromone frontalin (4) in the spruce beetle (SB), Dendroctonus rufipennis
      (Kirby), and (2) that frontalin and exo-brevicomin are produced from 3 and 1,
      respectively, only by beetles that utilize them as aggregation pheromones.
      Exposure of scolytids MPB, SB, pine engraver (PE), Ips pini (Say) and Ips tridens
      (Mannerheim) and West Indian sugar cane weevil (WISW), Metamasius hemipterus
      sericeus (Olivier) to deuterio- or protio-3 invariably resulted in the production
      of deuterio- or protio-4. Similarly, exposure of SB, WISW and I. tridens to 1
      resulted in the production of 2. We were unable to demonstrate the presence of 3
      in SB volatiles, nor were we able to demonstrate the conversion of 6-methyl-5
      hepten-2-one to 3 by SB. Production of enantiomerically enriched frontalin and
      exo-brevicomin by all the beetles exposed to respective precursors reveals
      widespread occurrence of nonspecific polysubstrate monooxidases in the
      Coleoptera.

PMID- 8733626
TI  - The integral role of triacyl glycerols in the biosynthesis of the aldehydic sex
      pheromones of Manduca sexta (L).
AB  - In a gland located near the tip of their abdomens, Manduca sexta females produce
      a pheromone blend comprised of hexadecanal, (Z)-9-hexadecenal, (Z)- and (E)-11
      hexadecenal, (E,Z)- and (E,E)-10,12-hexadecadienal, and (E,E,Z)- and (E,E,E)
      10,12,14-hexadecatrienal. These aldehydes are produced and released by
      evaporation from the surface of the gland only during a discrete period of the
      night. They are not stored in the gland and are found there only in very small
      amounts, if at all, during other times of the photoperiod. However, fatty acyl
      analogues of the pheromone aldehydes are present in the gland in relatively large
      amounts, primarily as components of triacyl glycerols, continuously from eclosion
      of the adults until death. The unsaturated components are produced from
      hexadecanoate, which is desaturated to the monoenes. Then, (Z)-11-hexadecenoate
      is desaturated and isomerized to form the conjugated dienes and ultimately the
      conjugated trienes. The fatty acyl precursors of the pheromones, stored as
      components of triacyl glycerols, are converted into aldehydes by a process
      triggered by a pheromone biosynthesis activating neuropeptide (PBAN), produced in
      the brain-subesophageal complex. It is not yet clear whether this conversion
      involves direct reduction of the acyl groups to aldehydes or reduction to
      alcohols followed by oxidation to aldehydes.

PMID- 8733627
TI  - Biosynthetic enzymes regulating ratios of sex pheromone components in female
      redbanded leafroller moths.
AB  - Changes in key enzymes in the biosynthetic pathways of sex pheromone components
      can produce differences in component ratios and structures. The sex pheromone
      communication system is critical to reproduction and the maintenance of a species
      and so changes in this system can play a major role in the speciation process.
      Artificial selection of female redbanded leafroller moths that produced either
      higher or lower ratios of 14-/12-carbon pheromone components was used to study
      how the biosynthetic pathways were affected in the high and low populations. The
      results showed that the chain shortening enzymes were selective for the (E)
      isomer and so left the 14-carbon acyl intermediates enriched in the (Z) isomer.
      Thus, the high population, which has a higher amount of 12-carbon components,
      also has a lower ratio of E11-/Z11-14:OAc pheromone components. The data also
      suggested that chain shortening occurred prior to reduction and acetylation of
      the 14-carbon components. These changes are not sufficient to isolate the
      redbanded leafroller populations, but we discuss some cases where significant
      changes in pheromone component ratios are affected by the chain-shortening
      enzymes.

PMID- 8733628
TI  - Difluoropalmitic acids as potential inhibitors of the biosynthesis of the sex
      pheromone of the Egyptian armyworm Spodoptera littoralis--IV.
AB  - 2,2-, 3,3- and 4,4-Difluoropalmitic acids (1-3) have been synthesized and fully
      characterized. Acids 2 and 3 were prepared through fluorination of the
      corresponding dithioacetal-protected ketoesters followed by enzymatic
      saponification. The acids 1-3 were evaluated in vivo as inhibitors of the beta
      oxidation step of the biosynthesis of (Z,E)-9,11-tetradecadienyl acetate, the
      major component of the sex pheromone of the Egyptian armyworm Spodoptera
      littoralis. Only, the 2,2- and 3,3-derivatives, i.e. those containing the two
      fluorine atoms at the positions involved in the chain-shortened step, have been
      found to be active, the activity being similar to or lower than that displayed by
      the corresponding monofluorinated acids.

PMID- 8733629
TI  - Ab initio calculations on (Z)-5-decenyl acetate, a component of the pheromone
      complex of Agrotis segetum (Lepidoptera: Noctuidae) and electrophysiological
      studies with chain elongated analogues.
AB  - Conformational analyses of (Z)-5-decenylacetate, a sex pheromone component of the
      turnip moth, Agrotis segetum, and double unsaturated pheromone analogues 4 and 5
      have been performed by ab initio calculations using Gaussian 92. Two minima were
      found for a cisoid and a transoid conformer, differing for 0.03 kcal/mol only.
      Conformational energies of diene analogues (5Z,7E)-5,7-decadienyl acetate (4) and
      (3E,5Z)-3,5,-decadienyl acetate (5) were determined for conformers required to
      mimic spatial relationships of the cisoid conformation of the natural pheromone
      2. Finally, single sensillum recording studies were carried out with chain
      elongated C11- to C16-pheromone analogues 6.

PMID- 8733630
TI  - New mimics of the acetate function in pheromone-based attraction.
AB  - Several analogues of (Z)-8-dodecenyl acetate (1a), the major pheromone component
      of the Oriental fruit moth, Cydia molesta, with chloroformate and lactone
      functional groups in place of the acetate moiety, were synthesized and
      investigated for their biological activity at four evaluation levels, i.e. by
      electroantennography (EAG), electrosensillography (ESG), short-range sexual
      stimulation and activation in the flight-tunnel. We found very strict
      requirements on the shape as well as on the electron distribution of the acetate
      group for a productive interaction with the receptor. The behavioral results
      showed that, among the analogues investigated, the chloroformate 1b, alken-4
      olide 2a and also dodecyl acetate (1c) possess significant (60-85%) inhibitory
      activities. Based on electrophysiological evidence demonstrating that (i) only 1b
      is competing with the major pheromone component 1a for the same receptor sites on
      the male antennal sensilla, (ii) 1c elicits moderate EAG but no ESG responses and
      (iii) 2a does not produce any electrophysiological response at all, three
      possible inhibitory mechanisms by which these analogues are acting could be
      distinguished.

PMID- 8733631
TI  - Antennal response and field attraction of the predator Elatophilus hebraicus
      (Hemiptera: Anthocoridae) to sex pheromones and analogues of three Matsucoccus
      spp. (Homoptera: Matsucoccidae).
AB  - The predator Elatophilus hebraicus is closely associated with its prey, the pine
      bast scale, Matsucoccus josephi, and utilizes the M. josephi sex pheromone as a
      kairomone. Kairomonal activity of E. hebraicus was studied by GC-EAD and field
      bioassays. The sex pheromone of M. josephi [2E,5R,6E,8E)-5,7-dimethyl-2,6,8
      decatrien-4-one [(R)-E-M.j.] elicited a strong EAD response and attracted large
      numbers of the predator. The sex pheromone of two allopatric Matsucoccus spp.,
      Matsucoccus feytaudi, (3S,7R,8E,10E)-3,7,9-trimethyl-8,10-dodecadien-6-one [(S,R)
      E-M.f.] and Matcucossus matsumurae, (2E, 4E,6R,10R)-4,6,10,12-tetramethyl-2,4
      tridecadien-7-one [(R,R)-E-M.m.], were also EAD-active and attracted significant
      numbers of E. hebraicus in the forest. Increasing the lure load of (S,R)-E-M.f.
      and (R,R)-E-M.m., in order to compensate for their lower volatility relative to
      (R)-E-M.j., resulted in similar attraction of E. hebraicus to each of the three
      pheromones. Other Matsucoccus pheromone stereoisomers displayed no behavioral
      activity. There was a significant difference in the activity of sex pheromone
      analogues, (6E/Z,8E)-5,7-dimethyl-6,8-decadien-4-one (52% E + 48% Z, ANLG 1) and
      (6E/Z,8E)-2,4,6-trimethyl- 1,6,8-nonatrien-3-one (60% E + 40% Z, ANLG 2). The (E)
      isomer of ANLG 1 evoked a strong EAD response from E. hebraicus and the mixture
      of E/Z ANLG 1 attracted the predator in moderate numbers, whereas ANLG 2 was
      inactive both in EAD and field tests. Conversely, M. josephi males were not
      attracted to M. feytaudi and M. matsumurae pheromones or pheromone analogues.
      Cross-activity of E. hebraicus to M. feytaudi and M. matsumurae pheromones may be
      based on structural similarity of the compounds. Alternatively, E. hebraicus may
      respond specifically to the pheromones of two allopatric Matsucoccus spp. If
      true, kairomonal attraction of E. hebraicus to these pheromones may have evolved
      during speciation of Matsucoccidae and may have been preserved despite the
      allopatry of M. josephi, M feytaudi and matsumurae.

PMID- 8733632
TI  - Optimization of blends of synthetic pheromone components for trapping male
      limabean pod borers (Etiella zinckenella Tr.) (Lepidoptera: Phycitidae):
      preliminary evidence on geographical differences.
AB  - From the five previously identified pheromone components of the limabean pod
      borer (Etiella zinckenella Tr.) (Lepidoptera: Phycitidae), the 100:3 mixture of
      (Z)-11-tetradecenyl acetate and (Z)-9-tetradecenyl acetate was necessary for
      maximal attraction of males into traps in tests performed in Hungary. The
      addition of (E)-11-tetradecenyl acetate in percentages higher than 10-30%
      generally had an adverse effect on catches, while the addition of the other two
      compounds present in pheromone extracts had no influence on catches. In contrast
      to the results in Hungary, none of the traps baited with combinations of the
      above compounds captured any moths in tests performed in Taiwan, suggesting
      possible geographical differences in pheromonal response of European and Eastern
      Asian populations of E. zinckenella.

PMID- 8733633
TI  - Conformationally constrained analogues of (Z)-5-decenyl acetate, a pheromone
      component of Agrotis segetum.
AB  - Conformationally constrained analogues of (Z)-5-decenyl acetate (1), a pheromone
      component of the turnip moth, Agrotis segetum, have been synthesized and tested
      by using electrophysiological single-cell recordings. In the constrained
      analogues the terminal alkyl chain in 1 has been incorporated in a six-membered
      (3 and 4) or five-membered (6) ring system. These cycli compounds are also
      conformationally constrained analogues of the previously deduced bioactive
      conformations of the corresponding chain-elongated analogues 2 and 5. The
      electrophysiological activities of the constrained analogues are found to be
      significantly lower than that of the natural pheromone component 1, most probably
      due to steric repulsive interactions between the analogue and the receptor, and
      also lower than the activities of the corresponding chain-elongated analogues of
      1. It is concluded that the flexibility of the terminal chains in 2 and 5 is
      essential for the possibility of the receptor to accommodate these parts of the
      chain-elongated analogues in their bioactive conformations.

PMID- 8733634
TI  - Proteins that smell: pheromone recognition and signal transduction.
AB  - Pheromone perception in Lepidoptera requires initial recognition and transport of
      the pheromone molecule by ligand-specific pheromone binding proteins (PBPs) in
      the moth antennae, followed by recognition of the ligand or PBP-ligand complex by
      a transmembrane G-protein-coupled odorant receptor protein. This signal is
      transduced by activation of a specific phospholipase C, intracellular release of
      inositol 1,4,5-trisphosphate (IP3) and IP3-gated opening of an ion channel.
      Individual pheromone-specific PBPs provide the initial ligand recognition event
      and encode ligand specificity. We have used photoaffinity labeling, cDNA library
      screening and cloning, protein expression, a novel binding assay and site
      directed mutagenesis to define the ligand specificity of PBPs.

PMID- 8733635
TI  - Labial gland chemistry of three species of bumblebees (Hymenoptera: Apidae) from
      North America.
AB  - The volatile secretion emanating from the cephalic part of the paired labial
      gland in male bumblebees of three North American species, viz. Bombus sonorus
      Say, Bombus huntii Greene and Psithyrus insularis (F. Smith) has been analysed by
      GC-MS and GC-FTIR. The secretion, which is deposited as a marking secretion on
      various objects along a repetitive flight path, is composed of isoprenoids,
      (acyclic sesqui- and diterpenes) and straight-chain fatty acid derivatives
      (alcohols containing 14, 16 and 18 carbon atoms, and odd numbered hydrocarbons
      ranging from 23 to 27 carbons). The secretions are species-specific with just a
      few major components. In B. sonorus (Z)-11-octadecen-1-ol is the main compound
      accompanied by geranylgeraniol and tetradecan-1-ol; in B. huntii the dominating
      compound is trans-2,3-dihydrofarnesol and it also contains (Z)-11-octadecen-1-ol
      and hexadecan-1-ol; P. insularis is characterized by geranylcitronellol, together
      with the (Z)-11-octadecen-1-ol and hexadecan-1-ol. These results agree with
      analyses of 36 species and two forms of Scandinavian bumblebees analysed
      previously.

PMID- 8733636
TI  - 1,3-butadiene in gasoline: an analytical confusion.

PMID- 8733637
TI  - CS2: another possible renal damaging solvent.

PMID- 8733638
TI  - A keyboard for "Daubert".

PMID- 8733639
TI  - Evidence for work-related musculoskeletal disorders: a scientific
      counterargument.

PMID- 8733640
TI  - The relationship of vitamin B6 status to median nerve function and carpal tunnel
      syndrome among active industrial workers.
AB  - Case reports and small case series suggest that vitamin B6 deficiency is an
      important etiologic factor in carpal tunnel syndrome (CTS). This hypothesis has
      never examined in a randomly selected study population, particularly among active
      workers. We examined 125 randomly selected active workers from two industrial
      plants. Each worker completed a self-administered symptom questionnaire and
      underwent electrodiagnostic testing of the median and ulnar sensory nerves.
      Laboratory biochemical analyses of vitamin B6 status were also performed using
      the erythrocyte glutamic pyruvic transaminase assay, and quantification of plasma
      pyridoxal-5'-phosphate. Measurements of vitamin B6 status were unrelated to self
      reported symptoms potentially consistent with CTS, electrophysiologically
      determined median or ulnar nerve function, and CTS defined on the basis of self
      reported symptoms and electrophysiologic measurements. These results suggest that
      CTS among active industrial workers is unrelated to vitamin B6 status.
      Furthermore, in our opinion, empiric prescription of vitamin B6 to patients with
      CTS is unwarranted and potentially hazardous.

PMID- 8733641
TI  - A 50-year mortality follow-up of a large cohort of oil refinery workers in Texas.
AB  - To investigate further the possible role of occupational exposures on mortality,
      an update of a large Texas petroleum refinery cohort was undertaken. Between 1937
      and 1987, 6799 deaths were identified among 17,844 employees. Relative to the
      general population of Texas, the overall standardized mortality ratio (SMR)
      showed a statistically significant deficit, as did nine other cause-of-death
      categories. Statistically significant mortality excesses were found for bone
      cancer (SMR = 207.8: 95% confidence interval [CI], 110.6 to 355.3), acute
      lymphocytic leukemia (ALL) (SMR = 259.6; 95% CI, 112.1 to 511.5), and
      benign/unspecified neoplasms (SMR = 194.9; 95% CI, 129.5 to 281.7). However, none
      of these diseases demonstrated an exposure-response relationship with length of
      employment. Subcohort mortality analyses by sex and race groups, length of
      employment, interval since hire, period of hire, and pay status were also
      performed. Overall, the update findings do not indicate that any excess mortality
      occurred as a result of employment at the refinery.

PMID- 8733642
TI  - Topical treatments for hydrofluoric acid dermal burns. Further assessment of
      efficacy using an experimental piq model.
AB  - Several topical treatments for hydrofluoric acid dermal burns (Zephiran, calcium
      acetate and magnesium hydroxide antacid soaks, and calcium gluconate gel) were
      assessed for efficacy in a pig model. Gross appearance and histopathology of
      treated and untreated burn sites were evaluated. For superficial burns, Zephiran
      was most effective; calcium acetate, magnesium hydroxide antacid, and calcium
      gluconate gel were less effective. For deep burns, gross observations showed that
      calcium acetate and Zephiran were most efficacious, whereas histopathology
      indicated comparable efficacy of Zephiran, calcium acetate, and calcium gluconate
      gel for all skin layers. Magnesium hydroxide antacid demonstrated efficacy only
      for the subdermis. The clinically beneficial effects of both Zephiran and calcium
      gluconate gel were affirmed. Although results suggest that calcium acetate and
      magnesium-containing antacids may be beneficial for human hydrofluoric acid
      dermal burns, these are not established clinical treatments.

PMID- 8733643
TI  - Personal health-risk predictors of occupational injury among 3415 municipal
      employees.
AB  - Little information exists about the effectiveness of health-promotion programs in
      reducing occupational injury rates. A historical cohort study was conducted to
      examine the relationship between personal health-risk factors and risk of
      occupational injury. Workers were grouped on the basis of nonoccupational risk
      taking behaviors, psychosocial risks, cardiovascular risk factors, and a total
      risk-factor variable. All analyses were controlled for sex, smoking status, age,
      and job classification. An increased risk of occupational injury (P < .0001) was
      found to be significantly associated with nonoccupational risk-taking behavior.
      This association may be the result of continued risk-taking behavior in the
      occupational environment, or assignment of risk-taking individuals to more
      hazardous job tasks. Psychosocial, cardiovascular, and total risk-factor
      variables were not associated with an increased risk of occupational injury.

PMID- 8733644
TI  - Airway function and respiratory symptoms in sanitation workers.
AB  - The prevalence of acute and chronic respiratory symptoms and lung-function
      changes was studied in a group of 81 municipal sanitation workers. In addition,
      the prevalence of chronic respiratory symptoms and lung function was studied in
      65 control workers. There were significantly higher prevalences of all chronic
      respiratory symptoms among the sanitation workers than among the control workers.
      Sanitation workers (smokers and nonsmokers) 40 years of age or older had higher
      prevalences of all chronic respiratory symptoms than younger workers. In
      addition, sanitation workers (both smokers and nonsmokers) employed for 10 years
      or longer had significantly higher prevalences of chronic respiratory symptoms
      than control workers. There was also a high prevalence of acute symptoms, which
      developed among the sanitation workers during work shifts. Of these symptoms,
      prevalences were highest for dryness of the nose and throat, followed by throat
      and eye irritation. Lung-function testing demonstrated significantly diminished
      forced vital capacity (FVC) and 1-second forced expiratory volume (FEV1) for the
      81 sanitation workers compared with control values. These differences only become
      significant after 10 or more years of employment in the sanitation industry and
      were not entirely explained by smoking. These differences were smaller and not
      statistically significant for maximum flow rates at 50% and the last 25% of the
      vital capacity. Our data suggest that sanitation worker--particularly those with
      long periods of work exposure--may develop acute and/or chronic respiratory
      symptoms accompanied by decreases in lung function (primarily FVC and FEV1).

PMID- 8733645
TI  - Prevalence of and potential risk factors for symptoms associated with insecticide
      use among animal groomers.
AB  - Pet groomers make numerous insecticide applications during the flea season, but
      few studies have examined their health complaints. The Pesticide Control Program
      of the New Jersey Department of Environmental Protection conducted a health and
      safety survey of this population. All licensed pet applicators in New Jersey were
      contacted, as were New Jersey veterinarians listed as pet-animal practitioners by
      the American Veterinary Medical Association. Approximately 36% of the respondents
      indicated that during the 1994 flea season, they had experience at least one of
      the 17 symptoms associated with insecticide application. Central nervous system
      symptoms (headache, dizziness, or confusion) and skin symptoms (skin rash or
      numbness/tingling) were reported most frequently. Logistic regression results
      suggest that applications per season, years as an applicator, certain hygiene
      variables, certain classes of products, and status of applicator (veterinary vs
      veterinary) are potentially important risk factors.

PMID- 8733646
TI  - Epidemiologic characteristics of participants and nonparticipants in health
      promotion programs.
AB  - There is potential for nonparticipation in health-promotion programs to impact on
      all overall success of these programs. The evidence on the relationship of
      participation of demographic and health characteristic is conflicting. The study
      presented here prospectively examined the relationship of personnel data and self
      reported smoking, exercise, and dietary behavior to participation in the initial
      phase of a new health-promotion program. Compared with the total population,
      participants tended to be older and more educated, to be foreign-born and of
      Eastern ethnic origin, and to have more children. The participant population also
      tended to include more women, married individuals, and noncommissioned officers.
      A low smoking prevalence (17% of the participants), a high mean exercise rate
      (four times per week), and low weekly mean egg consumption (2.7) were observed
      among the program participants. These results indicate that this program
      preferentially enrolled people who already were committed to healthy lifestyles,
      and did not reach all segments of the work force equally.

PMID- 8733647
TI  - The cytokine response to critical illness.
AB  - The aims of this review are to provide a basic introduction to the biology of
      cytokines and to summarise the results of studies, both laboratory and clinical,
      relating to the cytokine response to critical illness. Elucidation of the
      cytokine response to conditions such as sepsis, trauma, and burns may be
      important for several reasons. It may improve understanding of the
      pathophysiological processes triggered by these insults. It may allow the
      severity of the insult to be gauged, and maybe even provide prognostic
      information about individual patients. Similarly it may allow the effectiveness
      of resuscitation and further treatment to be monitored. Finally, knowing about
      the cytokine response may provide the key to developing new treatments.

PMID- 8733648
TI  - Short stay observation patients: general wards are inappropriate.
AB  - OBJECTIVE: To assess the efficiency of a short stay observation ward attached to
      the accident and emergency (A&E) department of a main teaching hospital. METHODS:
      The study was done on 107 patients admitted to the A&E observation ward and 107
      similar patients admitted to general wards after closure of the observation ward.
      Patients of 13 years and over who required short term admission to hospital for
      observation or investigation were included. RESULTS: Patients admitted to the A&E
      observation ward were seen sooner by a senior doctor, had fewer investigations,
      and had a shorter stay in hospital than similar patients admitted to the general
      wards. CONCLUSIONS: The A&E observation ward was more efficient than the general
      acute wards at dealing with short stay patients.

PMID- 8733649
TI  - Drug history taking and the identification of drug related problems in an
      accident and emergency department.
AB  - OBJECTIVE: To determine the incidence of drug related problems that fail to be
      noted on casualty cards in patients subsequently admitted, and to compare
      medication histories as recorded by accident and emergency (A&E) senior house
      officers (SHOs) and a pharmacist. METHODS: An initial retrospective survey of
      1459 acute inpatient admissions through A&E over a three month period was
      followed by a prospective study of 33 elderly patients. RESULTS: In the
      retrospective survey, 52 medication related problems were confirmed after
      examination of the medical records, of which only 16 were identified in A&E. In
      the prospective study, 125 currently prescribed items were identified by the
      pharmacist compared to 77 by A&E SHOs; 66% of the missed information was
      clinically relevant. Of 17 previous adverse drug reactions identified by the
      pharmacist only six were also recorded by the A&E officer. Only four over the
      counter medicines were identified by the A&E SHOs compared to 30 by the
      pharmacist. CONCLUSIONS: More accurate recording of drug history on casualty
      cards should be undertaken, particularly in respect of over the counter
      medication and the identification of drug related problems.

PMID- 8733650
TI  - Reviews in accident and emergency medicine: the past and the future.
AB  - OBJECTIVE: To determine whether reviews published in the past 10 years are as
      helpful as they could be to their readers, and to explain why future reviews
      should meet certain methodological criteria. METHODS: The quality of 16 reviews
      published in two journals dealing with accident and emergency medicine over 10
      years was objectively assessed using 11 currently recommended criteria. RESULTS:
      The median number of methodological criteria satisfied was two. Only five of the
      reviews posed a specific question or problem and then answered this with
      conclusions based on evidence presented. CONCLUSIONS: If reviews are to enhance
      patient care, the way in which they are performed, written and used must change.

PMID- 8733651
TI  - Traumatic pneumothorax: is a chest drain always necessary?
AB  - OBJECTIVE: To examine the management of traumatic pneumothorax in a department
      where some of these injuries do not receive chest drains. METHODS: A
      retrospective study of the management of traumatic pneumothorax was performed on
      a unit where historically many of these injuries have been treated
      conservatively. RESULTS: 54 pneumothoraces in a three year period were
      identified. Of these, 29 injuries (54.7%) were initially managed without
      drainage. Two patients subsequently had chest drains inserted as a result of
      asymptomatic radiological enlargement of the pneumothorax while inpatients. No
      patients deteriorated clinically during conservative treatment. CONCLUSIONS:
      Chest drain insertion for small or moderate sized traumatic pneumothoraces, in
      the absence of other significant injuries or the need for intermittent positive
      pressure ventilation (IPPV), may be unnecessary.

PMID- 8733652
TI  - Cervical spine imaging in trauma patients: a simple scheme of rationalising arm
      traction using zonal divisions of the vertebral bodies.
AB  - OBJECTIVE: To evaluate the effectiveness of arm traction for cervical spine
      imaging in trauma patients and devise a scheme to predict the probability of
      visualising the C7/T1 level in trauma patients. METHODS: 98 trauma patients were
      studied. Each vertebral body was divided into three equal horizontal zones, the
      disc space between vertebral bodies being equivalent to one zone. The fifth
      cervical vertebra was used as the starting level (zone 1). Zones obtained pre and
      post arm traction on the lateral cervical spine radiographs were recorded.
      Results were analysed to show the probability of imaging the lower cervical
      spine, including the cervico-thoracic junction. RESULTS: If the initial film
      showed less than zone 10 (mid-C7 vertebra), the probability of showing zone 13
      (upper body of T1) with arm traction was only 7.7%, that is, one success in every
      13 pulls; or conversely, 12 failures in every 13 pulls. CONCLUSIONS: Unless an
      initial cervical spine radiograph includes the upper one third of the body of the
      C7 vertebra, the probability of attaining the C7/T1 level with arm traction is <
      15%. It is suggested that all initial radiographs of the lateral cervical spine
      in major trauma patients be done with arm traction, and where the upper one third
      of the body of C7 vertebra is not seen, then computerised tomography, swimmer's,
      or oblique views be considered.

PMID- 8733653
TI  - A protocol to improve analgesia use in the accident and emergency department.
AB  - OBJECTIVE: To assess the use of analgesia in an accident and emergency (A&E)
      department and identify shortcomings. SETTING: University teaching hospital.
      METHODS: An audit of patients referred from the A&E department to orthopaedic
      fracture clinic (n = 100) or for orthopaedic admission (n = 100) was carried out
      to document analgesia use. An analgesia protocol was introduced and analgesia use
      was reassessed on the same numbers of patients. RESULTS: Prescribing of analgesia
      was initially poor: 91% of fracture clinic referrals and 39% of admissions
      received no analgesia while in the A&E department; when given, it was often by
      inappropriate routes. Introduction of an analgesia protocol significantly
      improved analgesia use: fracture clinic referrals receiving unsatisfactory
      analgesia were reduced from 91% to 69% (P < 0.001). There was a marked increase
      in the use of intravenous analgesia, from 9% to 37% (P < 0.001). CONCLUSIONS:
      Large numbers of patients still receive no analgesia while in the A&E department.
      This seems to be a common problem requiring intervention at a national level. The
      absence of a coordinated approach to improving analgesia provision for acute
      trauma in the United Kingdom should be addressed urgently.

PMID- 8733654
TI  - Use of a psychiatric proforma for accident and emergency officers.
AB  - OBJECTIVE: To devise a proforma for clinical documentation of psychiatric illness
      in an accident and emergency (A&E) department, since A&E senior house officers
      (SHOs) have little psychiatric experience before starting their jobs. METHODS:
      History taking and mental state examinations by 16 SHOs were compared before (n =
      50) and after (n = 50) the introduction of the proforma. Comments on the proforma
      were provided by all participants on a questionnaire. RESULTS: There was an
      improvement in documentation with the use of the proforma (Mann-Whitney U test, P
      < 0.001). The senior house officers found the proforma useful and supported
      further development of this initiative. CONCLUSIONS: A standard form for
      documenting psychiatric history, designed according to local needs, is useful and
      should be available in A&E departments.

PMID- 8733655
TI  - Tetanus immunisation in the elderly population.
AB  - OBJECTIVE: To emphasise that tetanus still occurs in the United Kingdom,
      particularly in elderly people-as illustrated by two case reports-and to examine
      the state of tetanus immunity in elderly people. METHODS: 111 elderly people
      (over 65 years) were studied: 43 males, mean age 77.7 years, range 67-94; 68
      females, mean age 81.3 years, range 67-95. They were either attending the
      accident service or were hospital inpatients. An attempt was made to obtain an
      immunisation history and antitetanus antibody titres were measured. RESULTS:
      Immunisation history was uncertain and unreliable. Measurement of antibody titres
      showed that they were inadequate to ensure protection in 50% of those studied.
      Low levels were particularly prevalent in the over 80 age group and in females.
      Questioning about military service confirmed that this had predominantly involved
      males. CONCLUSIONS: Elderly people are at risk of contracting tetanus and should
      be targeted for community immunisation. Extra precautions in the form of passive
      immunisation with human anti-tetanus immunoglobulin should be used in this age
      group in addition to the usual wound management measures when the elderly sustain
      tetanus prone injuries.

PMID- 8733656
TI  - Topical analgesia for superficial corneal injuries.
AB  - OBJECTIVE: To assess the analgesic effects of a topical non-steroidal anti
      inflammatory agent, flurbiprofen 0.03%, during healing after superficial corneal
      injuries. METHODS: 401 patients treated for corneal abrasion in a five month
      period were randomly allocated to one of four treatment groups: polyvinyl alcohol
      alone (control), homatropine 2%, flurbiprofen 0.03%, or homatropine 2% followed
      by flurbiprofen 0.03%. Treatments were given for 48 h. Ocular pain was recorded
      on a visual analogue scale by the patients over the first 24 h, and use of oral
      analgesics was also recorded. Usable responses were received from 224 patients
      (55.8%). RESULTS: Patients treated with flurbiprofen had significantly lower pain
      scores for the 24 h duration of the study than controls (P < 0.05). CONCLUSIONS:
      Flurbiprofen eye drops provide more effective pain relief than traditional
      treatments for superficial corneal injuries.

PMID- 8733657
TI  - An investigation into the effects of British Summer Time on road traffic accident
      casualties in Cheshire.
AB  - OBJECTIVE: To assess the effect of British Summer Time (BST) on road traffic
      accident casualties and to analyse whether the introduction of year round BST
      would result in reductions in casualty numbers. DESIGN: A comparative study of
      road traffic accident data from before and after the onset of BST. SETTING: The
      county of Cheshire. SUBJECT: Data from a total of 4185 casualties from the period
      1983 to 1993. MAIN OUTCOME MEASURES: The effect of BST on both vehicle, cycle,
      and pedestrian casualties and casualties among schoolchildren. RESULTS: The onset
      of BST in spring was associated with reductions in casualty numbers of 6% in the
      morning and 11% in the evening. The anticipated rise in casualties with the
      darker mornings was not seen and as reductions were maximal in the pedestrian
      (36%), cyclist (11%), and schoolchild (24%) subgroups they were presumed to be
      due to an altered reliance on vehicular transport. The change back to Greenwich
      Mean Time (GMT) in autumn produced an anticipated reduction (6%) in casualties in
      the lighter mornings. The darker evenings, as predicted, were associated with
      significant increases in casualties (4%), mainly vehicle (5%) and pedestrian (8%)
      casualties. There was an overall net reduction in casualty numbers when the
      analysed periods of BST were compared to those during GMT. CONCLUSIONS: The use
      of BST in Cheshire over the period studied was associated with reductions in
      casualty figures. The application of these results nationally may be expected to
      produce more and less pronounced changes the further north or south,
      respectively, the area studied. The introduction of year-long BST would result in
      beneficial effects on road traffic accident casualties.

PMID- 8733658
TI  - First aid treatment of epistaxis--are the patients well informed?
AB  - OBJECTIVE: To investigate the level of lay knowledge of first aid measures for
      epistaxis, and to determine the effectiveness of an ENT department policy of
      providing an advice sheet of first aid measures. METHODS: 50 patients presenting
      with epistaxis were questioned on the accuracy and level of their knowledge of
      the four basic procedures used to combat a nose-bleed. The results were
      correlated with the source of referral, previous treatment, and advice. RESULTS:
      A large proportion of patients who had previously been treated for epistaxis by
      their general practitioners and other non-ENT trained medical or nursing staff
      were unable to recall being given any first aid advice. For those who remembered
      being given advice, very few described all the steps correctly. In contrast,
      patients who had previously been seen by the ENT staff scored full points in
      every aspect. CONCLUSIONS: The results are a reflection of the departmental
      policy of supplying information sheets outlining the first aid measures to all
      patients presenting with epistaxis.

PMID- 8733659
TI  - Are schools safer for children than public places?
AB  - OBJECTIVE: To investigate the frequency and severity of accidents to children in
      schools. METHODS: Retrospective analysis of accidents occurring in school over a
      six month period and resulting in attendance at an accident and emergency
      department. Comparison was made with accidents occurring in public places,
      RESULTS: During the study period there were 127 school and 251 public place
      accidents causing fractures or dislocations requiring hospital treatment in 3-16
      year old children; 22.4% (127/567) of all injuries at school resulted in
      fractures or dislocations, as opposed to 20.8% (251/1197) of those sustained in
      public places. CONCLUSIONS: Injuries at school are a cause for concern as they
      occur in a supervised environment and this should be the target of accident
      prevention measures.

PMID- 8733660
TI  - Comparison of cardiopulmonary resuscitation techniques using video camera
      recordings.
AB  - OBJECTIVE: To use video recordings to compare the performance of resuscitation
      teams in relation to their previous training in cardiac resuscitation. METHODS:
      Over a 10 month period all cardiopulmonary resuscitations carried out in an
      accident and emergency (A&E) resuscitation room were videotaped. The following
      variables were monitored: (1) time to perform three defibrillatory shocks; (2)
      time to give intravenous adrenaline (centrally or peripherally); (3) the numbers
      and grade of medical and nursing staff involved in the resuscitation; (4) the
      experience and training of these personnel. RESULTS: Of 101 resuscitations
      recorded, 69 were carried out by the A&E team alone and 32 by the hospital
      cardiac arrest team. Resuscitation procedures were carried out significantly more
      rapidly by the former. Skills and protocols were most effectively used when the
      resuscitation team was led by an experienced doctor who had received specific
      training in cardiopulmonary resuscitation, that is, Advanced Life Support course
      (ALS) or Advanced Cardiac Life Support course (ACLS). Such an individual was
      always present at A&E team resuscitations but in only 6% of cardiac arrest team
      resuscitations. CONCLUSIONS: ALS course completion should be regarded as a vital
      part of the training of any doctor involved in cardiopulmonary resuscitation.

PMID- 8733661
TI  - Sarin: guidelines on the management of victims of a nerve gas attack.
AB  - Sarin is now a weapon of the terrorist. Its acute effects are primarily due to
      unrestricted cholinergic activity at both muscarinic and nicotinic receptors.
      Treatment is based on the use of large doses of atropine and pralidoxime which
      may lead to practical problems of sufficient drug supplies for the average
      hospital. Ventilation may be necessary and present problems. Victim
      decontamination involves use of bleach, soap and water. Staff handling casualties
      need protection with respirators and butyl rubber boots and gloves.

PMID- 8733662
TI  - Scalp lacerations demand careful attention before interhospital transfer of head
      injured patients.
AB  - Blood loss from scalp lacerations may be considerable. Two cases are described to
      illustrate the hazards of transferring patients with head injuries without
      adequate attention to scalp wounds. In such cases referring clinicians must be
      satisfied that haemostasis is secure. Failure to do this may place the patient at
      increased risk as a result of the need for additional resuscitation, and
      therefore delay the definitive management.

PMID- 8733663
TI  - Warfarin and the apparent minor head injury.
AB  - Two cases of patients on warfarin who developed intracranial haematoma after an
      apparently minor head injury are described. There is a 10-fold increase in the
      likelihood of developing an intracranial haematoma in these patients.
      Recommendations are made regarding the management of this type of patient seen in
      the accident and emergency department.

PMID- 8733664
TI  - Nail gun injury: a barbed problem.
AB  - A case of nail gun injury is reported. Preoperative radiographs are essential to
      determine whether copper barbs project from the nail shaft before any attempt is
      made to remove the nail. Thorough exploration is required.

PMID- 8733665
TI  - Erythema nodosum--diagnostic difficulties in the accident and emergency
      department.
AB  - Five patients presenting with erythema nodosum to an accident and emergency
      department are described. Initially they were misdiagnosed as cellulitis,
      infected insect bites, and minor trauma. Suspicious skin lesions or joint
      manifestations occurring either alone or especially if in combination should
      alert the wary clinician to the possibility of erythema nodosum and follow up in
      a few days may help to confirm the diagnosis.

PMID- 8733666
TI  - A confused drug addict: the importance of considering sepsis.
AB  - The case is reported of a 35 year old heroin addict presenting with acute
      confusion which was later found to be due to meningococcal meningitis. Other than
      his altered mental state, the only abnormal finding on examination was a mild
      pyrexia.

PMID- 8733667
TI  - Perilunate fracture-dislocation: a continually missed injury.
AB  - Five cases of perilunate fracture-dislocation are presented in which the
      radiological appearances were typical but the diagnoses were initially missed. A
      simple systematic method of x ray analysis is described.

PMID- 8733668
TI  - Scapholunate instability--a spectrum of pathology.
AB  - Five cases of scapholunate instability are reported. The condition is commonly
      misdiagnosed in accident and emergency departments. The importance of a complete
      clinical assessment of the suspected scaphoid injury and the need to measure the
      scapholunate distance and the scapholunate angle on the radiographs is stressed.

PMID- 8733669
TI  - Tension pneumoperitoneum.
AB  - Tension pneumoperitoneum developing in a middle aged asthmatic male during
      resuscitation after a respiratory arrest is reported. This was associated with
      bilateral tension pneumothorax and caused severe respiratory embarrassment which
      was relieved by needle decompression, after decompression of the pneumothoraces.
      The chest is not the only body cavity that can contain air under tension.

PMID- 8733670
TI  - Dystonic reactions: two case reports.
AB  - Case reports of dystonic reactions to metoclopramide are presented. Dystonic
      reactions may occur after ingestion of many drugs and should be considered by
      accident and emergency staff in patients with a suggestive clinical presentation.

PMID- 8733671
TI  - Missed cervical spine injury following barflying.
AB  - The case is reported of a young woman who suffered a wedge fracture of C7 due to
      axial loading with a flexed spine, in an injury caused by barfly jumping. The
      fracture was unstable and required surgical stabilisation. In this case the
      seriousness of the injury was not realised at first because neck radiographs were
      not taken at her initial assessment in accident and emergency.

PMID- 8733672
TI  - Stingray injury.
AB  - A case of stingray injury is reported. Local symptoms and signs include intense
      pain, oedema around the wound, erythema and petechiae. Systemic symptoms and
      signs include nausea and vomiting, muscle cramps, diaphoresis, syncope, headache,
      muscle fasciculations, and cardiac arrhythmias. Treatment aims to reverse local
      and systemic effects of the venom, alleviate pain, and prevent infection.
      Antitetanus prophylaxis is important. Treatment for anaphylaxis may be necessary.

PMID- 8733673
TI  - Oesophageal rupture in the course of conservative treatment of bleeding
      oesophageal varices.
AB  - Fatal oesophageal rupture is described as a complication of the management of
      bleeding oesophageal varices with repeated sclerotherapy and tamponade using the
      Sengstaken-Blakemore tube. The importance of chest radiographs is stressed in the
      early detection and prevention of malposition of the Sengstaken-Blakemore tube,
      as inflation of the gastric balloon in the oesophagus can result in oesophageal
      rupture.

PMID- 8733674
TI  - Heterotopic bone formation within a missile track.
AB  - A case is presented which is thought to be the first described example of
      heterotopic ossification occurring within the path of a bullet. Although the
      information was not available from prior medical records, the bullet presumably
      passed though bone or periosteum, thereby seeding the permanent cavity and
      facilitating ossification within the surrounding muscle and soft tissue.

PMID- 8733675
TI  - Thrombolysis in accident and emergency.

PMID- 8733676
TI  - Teaching advanced life support skills.

PMID- 8733677
TI  - Temporary A&E at the Whittington.

PMID- 8733678
TI  - Skin necrosis in prolonged application of an elasticated wrist splint in a
      psychiatric patient.

PMID- 8733679
TI  - Removal of fishbones in the throat.

PMID- 8733680
TI  - The evolution of clinical peripheral blood stem cell transplantation.
AB  - Our growing physiological understanding of hematopoietic progenitor cells has led
      to the clinical use of circulating progenitor cells, including stem cells, for
      either reconstitution of hematopoietic function, up to the transduction of
      functional genes into a self-renewing cell system. In the following, an attempt
      has been made to recollect the major steps in the evolution of clinical blood
      stem transplantation, from the morphological description of small lymphocytes
      circulating in the blood up to somatic gene therapy covering a time period of 87
      years.

PMID- 8733681
TI  - Granisetron in the prevention of vomiting induced by conditioning for stem cell
      transplantation: a prospective randomized study.
AB  - We conducted a prospective randomized study to compare granisetron, a 5
      hydroxytryptamine-3 receptor antagonist with standard anti-emetics (control
      group) consisting mainly of metoclopramide, in the prophylaxis of emesis induced
      by conditioning prior to stem cell transplantation. Fifty-eight patients were
      evaluable for analysis. The number of emetic episodes expressed in terms of
      patient-days was significantly lower in the granisetron group than in the control
      group (P < 0.001). During the first 24 h of conditioning, 27 of the 31 patients
      (87.1%) in the granisetron group achieved control of emesis with less than three
      emetic episodes (major < or = ) a day compared with 37.0% in the control group (P
      < 0.001). The same degree of emesis control was maintained throughout the
      conditioning period in 51.% of patients in the granisetron group compared with 0%
      in the control group (P < 0.001). Adverse reactions were observed in 11.4% of
      patients in the granisetron group and in 25.9% in the control group. None of the
      events were serious. Based on these data, we conclude that granisetron is
      superior to standard antiemetics in protecting against the vomiting induced by
      conditioning for stem cell transplantation.

PMID- 8733682
TI  - Unrelated allogeneic bone marrow transplantation using high-dose busulfan and
      cyclophosphamide (BU-CY) for the preparative regimen.
AB  - This study reviews results of a radiation-free preparative regimen consisting of
      busulfan and cyclophosphamide in 65 unrelated allogeneic bone marrow transplant
      recipients. Thirty-eight patients had chronic myelogenous leukemia (17 patients
      chronic phase, 13 patients accelerated phase, eight patients blast phase), 19
      patients had acute leukemia (second complete remission or relapse) and eight
      patients had myelodysplasia. The patients were transplanted at four different
      medical centers from July 1988 to November 1992. Ages ranged 4-48 years (median
      32). Fifty-seven patients received busulfan 16 mg/kg and cyclophosphamide 120
      mg/kg, and eight received busulfan at doses between 15 and 17 mg/kg and
      cyclophosphamide at doses 100-200 mg/kg as preparative regimens. All patients
      received cyclosporine for graft-versus-host disease prophylaxis; in addition 46
      patients received corticosteroid, 38 methotrexate, six anti-CD5 ricin A
      immunotoxin, and four T cell-depleted bone marrow. Median follow-up of survivors
      was 53 months (range 15-68 months). Four year actuarial survival was 24 +/- 12%.
      Four-year survival based on disease was 29 +/- 27% for chronic myelogenous
      leukemia (CML) in chronic phase, 20 +/- 9% for chronic myelogenous leukemia in
      accelerated phase, 0% for chronic myelogenous leukemia in blast phase, 32 +/- 40%
      for acute leukemia, and 38 +/- 34% for myelodysplasia. Actuarial survival was 66
      +/- 40% in patients age < 20 years, vs 23 +/- 13% for patients ages 20 to 40, and
      10 +/- 14% for patients age > 40 years. Fifty patients (88%) engrafted. Graft
      failure occurred in eight patients. Acute graft-versus-host disease grade II-IV
      occurred in 36 (72%). Two patients relapsed after engraftment with the donor
      cells and died of leukemia within a month of relapse. The most common causes of
      death were graft-versus-host disease (37%), and transplant-related toxicity
      (59%); relapse (4%) was a rare cause of death. Busulfan/cyclophosphamide is an
      effective preparative regimen in unrelated bone marrow transplantation permitting
      adequate engraftment and a low relapse rate. Best results are observed in
      patients less than 20 years old.

PMID- 8733683
TI  - Mobilization of peripheral blood progenitor cells with high-dose cyclophosphamide
      (4 or 7 g/m2) and granulocyte colony-stimulating factor in patients with multiple
      myeloma.
AB  - High-dose cyclophosphamide (HD-CY) has been shown to decrease the tumor mass in
      multiple myeloma (MM) patients and to be effective in the mobilization of PBPC.
      By administering hematopoietic growth factor the quantity of progenitor cells in
      the peripheral blood increased and the hematological toxicity of CY could be
      reduced. Thirty-two patients with stage II and stage III MM were treated to
      mobilize and harvest a sufficient amount of PBPC for autologous transplantation.
      Sixteen patients received 4 g/m2 CY and 16 patients 7 g/m2 CY in divided doses of
      1 g/m2 every 2 h. Both patient groups were comparable for disease stages as well
      as previous therapies. Twenty-four hours after chemotherapy 300 micrograms GCSF
      were administered subcutaneously once daily until the last day of leukapheresis.
      Administration of 7 g/m2 HD-CY resulted in statistically significantly higher
      peak values for CD34+ progenitor cells (47.86/microliters vs 18.75/microliters, P
      = 0.0198) in the peripheral blood. PBPC autografts containing > 2.5 x 10(6) CD34+
      cells/kg BW could be obtained at the first attempt from 14 of 16 patients treated
      with 7 g/m2 CY as compared to 10 of 16 patients treated with 4 g/m2 CY (P =
      0.11). The analysis of potentially malignant CD19+ B cells showed a highly
      significant lower mean CD19+ cell content/kg BW per leukapheresis in the 7 g/m2
      compared to the 4 g/m2 CY group (0.75 vs 1.81 x 10(6), P = 0.001). WHO grade IV
      treatment-related non-hematologic toxicity was not observed. We prefer the 7 g/m2
      CY dosage followed by cytokine administration for the mobilization of PBPC in
      advanced state MM patients pretreated with alkylating agents.

PMID- 8733684
TI  - Microbial contamination of peripheral blood stem cell collections.
AB  - We prospectively evaluated microbiologic cultures for a series of 1263 peripheral
      blood stem cell harvests collected from 376 sequential patients. The incidence of
      microbial contamination was 0.23% of all samples, or 47% of samples from patients
      not receiving systemic antibiotics. This incidence of positive microbial cultures
      is less than that for cultures of bone marrow (3.8%) after harvesting and before
      further processing. Of the three positive cultures, two grew coagulase-negative
      Staphylococcus and the third, Streptococcus viridans. Two patients were reinfused
      with cultured-positive PBSC components, and neither exhibited the same organism
      in subsequent blood cultures. Although microbial contamination may occur during
      peripheral blood stem cell collection and cryopreservation, this report indicates
      that PBSC contamination does not play a conspicuous role in the infectious
      complications of PBSC transplantation.

PMID- 8733685
TI  - Allogeneic blood cell transplants for haematological malignancy: preliminary
      comparison of outcomes with bone marrow transplantation.
AB  - Twenty-six patients with haematological malignancy received cryopreserved but
      otherwise unmanipulated blood cell transplants (BCT) from five- or six-antigen
      matched siblings in whom progenitor cells had been mobilized by G-CSF. Outcomes
      were compared with a historical control group of 26 BMT patients matched for age
      and disease status. Granulocyte counts recovered to 0.5 x 10(9)/l in a median of
      16 days after BCT compared with 21.5 days after BMT (P = 0.0002). Platelet
      counts, unsupported for 3 days, reached 20 x 10(9)/l in a median of 14 days vs
      20.5 days (P = 0.0003) after BCT compared with BMT in those patients who
      engrafted. In the BCT and BMT groups, respectively, the risk of grade II-IV acute
      GVHD was 37 vs 21% (P = 0.16) and of chronic GVHD at 1 year 53 vs 48% (P = 0.9).
      There was no significant difference in red cell transfusions but BCT patients
      required fewer platelet transfusions (median 3 vs 5, P = 0.015) and fewer days in
      hospital (20.5 vs 25, P = 0.02). These results indicate that allogeneic BCT from
      matched and partially mismatched family donors result in faster engraftment than
      BMT without a significant increase in GVHD. Allogeneic BCT may prove to be a more
      tolerable procedure than BMT for both donor and recipient and there are
      indications of improved cost-effectiveness.

PMID- 8733686
TI  - Increase of mobilized CD34-positive peripheral blood progenitor cells in patients
      with Hodgkin's disease, non-Hodgkin's lymphoma, and cancer of the testis.
AB  - G-CSF (filgrastim) can effectively mobilize peripheral blood progenitor cells
      (PBPC) when administered during steady-state hematopoiesis. In this single center
      study, we compared the effectiveness of two different doses of G-CSF on the
      mobilization of peripheral blood stem cells in patients with Hodgkin's disease,
      non-Hodgkin's lymphoma, and cancer of the testis. A first group including 33
      patients received 10 micrograms G-CSF/kg BW per day (group A), whereas a second
      group comprising 34 patients was treated with 24 (2 x 12) micrograms G-CSF/kg
      body weight (BW) per day (group B) prior to the leukapheresis. A significant
      difference (P = 0.015) in the total number of CD34+ cells between group A: 11.32
      x 10(7) (range 0.34-110.2) and group B: 48.25 x 10(7) (range 1.33-447.4) has been
      observed in the first leukapheresis product. Moreover, the total number of CFU-GM
      increased significantly from 34.79 x 10(4) (range 1.07-300.9) to 147.69 x 10(4)
      (range 1.03- 1204.0) (P < 0.005), and the number of MNC increased from 1.35 x
      10(10) (range 0.41-3.09) group A) to 2.93 x 10(10) (range 0.66-9.7) (group B) (P
      < 0.001). Comparable results were obtained in the second leukapheresis. Our data
      indicate, that the application of higher doses of G-CSF can significantly improve
      the effectiveness of mobilizing PBPC during steady-state conditions, and thereby
      considerably contribute to a safe and fast engraftment as well as a reduced
      number of leukapheresis procedures to achieve sufficient number of PBPC.

PMID- 8733687
TI  - High-dose chemotherapy and autologous peripheral blood progenitor cell transplant
      for the treatment of Hodgkin's disease.
AB  - This paper evaluates a comprehensive strategy of chemotherapy mobilization of
      peripheral blood progenitor cells (PBPCs) followed by high-dose chemotherapy for
      the treatment of refractory or relapsed Hodgkin's disease (HD). Patients with
      relapsed or refractory HD were enrolled to receive cyclophosphamide, etoposide +/
      cisplatin (CE +/- P) and rhG-CSF mobilization of PBPCs. Patients achieving < or
      = 2.5 x 10(6) CD34+ cells/kg following initial mobilization were eligible to
      receive a second course of CE +/- P. Unmanipulated PBPCs alone were infused
      following administration of high-dose carmustine, etoposide, cytarabine
      arabinoside and cyclophosphamide (BEAC). Thirty-eight consecutive patients with
      relapsed or refractory HD were initially enrolled to receive CE +/- P. Analysis
      was performed on an intent-to-treat basis. A median of 6.4 x 10(6) CD34+ cells/kg
      (range 0.66-62.3) were collected with a median of 3 (range 2-9) leukaphereses.
      Twenty-eight of 38 (74%) patients achieved > or = 2.5 x 10(6) CD34+ cells/kg.
      Analysis of variables potentially effecting mobilization of CD34+ cells revealed
      that only the amount of prior chemotherapy statistically influenced collecting
      CD34+ cells (P = 0.005). Two of six patients undergoing a second mobilization
      procedure achieved > or = 2.5 x 10(6) CD34+ cells/kg for a total of 30 patients
      eligible to proceed with high-dose BEAC. The 3-year Kaplan-Meier estimate of
      overall survival (OS) and progression-free survival (PFS) for all 38 patients is
      65 and 53%, respectively. The 3-year OS and PFS for the 28 patients receiving
      BEAC is 77 and 64% respectively vs 33 and 30% for the 10 patients not receiving
      BEAC. The strategy of CE +/- P and BEAC was well tolerated with a 100-day
      treatment-related mortality of 3.6%. All patients experienced rapid and sustained
      hematologic recovery with PBPCs alone. The median time to an ANC > or = 5 x
      10(9)/1 and platelet transfusion independence was 10 days. Although development
      of better strategies to mobilize PBPCs may benefit additional patients, currently
      the best strategy to collect PBPCs is early before patients have received
      extensive chemotherapy treatment. Collection of PBPCs immediately following
      initial relapse or induction failure using CE +/- P for PBPC mobilization allows
      sufficient PBPCs to be collected in greater than 90% of patients. Treatment of
      refractory or relapsed HD utilizing a strategy of CE +/- P PBPC mobilization for
      hematopoietic reconstitution following high-dose BEAC is associated with
      acceptable toxicity and rapid engraftment. A 3-year PFS greater than 60% can be
      achieved in the community hospital setting.

PMID- 8733688
TI  - Peripheral blood stem cell transplantation in myeloma using CD34 selected cells.
AB  - We have performed nine CD34 selection procedures on peripheral blood stem cells
      harvested from eight patients with myeloma using the Cellpro avidin-biotin
      immunoaffinity column (Ceprate). They all received CVAMP chemotherapy to maximum
      response prior to mobilisation. Six of the patients have been transplanted using
      these cells, one receiving successive autografts. Median absolute cell numbers
      processed and retrieved were: 31.1 x 10(9) pre-column, 2.07 x 10(8) in the final
      product and 30.4 x 10(9) in the column waste. Mean CD34 positivity in the product
      was 49% (range 18.4-98) with a median CD34+ yield of 31.4% (range 21-37.8). IgH
      PCR was performed and seven of the eight patients were amplifiable. Of these, two
      were positive in the pre-column product and both of these were successfully
      purged with a negative result in the final, post-column product. Patients were
      transplanted with a median of 2.0 x 10(6) CD34+ cells/kg (range 1.5-9.4)
      following conditioning with melphalan 200 mg/m2. The mean time to recovery of
      neutrophils to > 0.5 x 10(9)/l and platelets to > 20 x 10(9)/l was 16 and 17
      days, respectively. At a mean follow-up of 9 months, four of the six patients
      transplanted are alive, three of them in complete remission and one in a
      clinically stable relapse. One has died of disease relapse and one of progressive
      neurological problems the aetiology of which was uncertain but there was no sign
      of progression of their myeloma. We conclude that PBSCT using CD34 selected cells
      is safe and practical in myeloma following remission induction with CVAMP
      chemotherapy.

PMID- 8733689
TI  - Interleukin-2 before and/or after autologous bone marrow transplantation for
      pediatric acute leukemia patients.
AB  - The role of ABMT in the treatment of acute leukemia patients with poor prognosis
      is controversial because of the high risk of relapse. We attempted to obtain an
      anti-tumor effect by administering rIL-2 pre- and/or post-ABMT. We report our
      experience in 10 consecutive pediatric patients: two AML late responders and
      eight ALL in 2nd or subsequent CR who received ABMT and rIL-2. Five patients
      (group A) received rIL-2 only post-ABMT. A 120 h/week rIL-2 'induction' cycle at
      6 x 10(6) IU/m2/24 h was administered by continuous intravenous infusion for 2
      weeks. A further six maintenance rIL-2 cycles at 18 x 10(6) IU/m2/24 h were given
      72 h/week on a monthly basis. Five patients (group B) received a single 120 h
      cycle of rIL-2 at 6 x 10(6)/m2/24 h before BM harvesting. Three of the five group
      B patients entered the same protocol described above after ABMT. Increased NK and
      LAK activity were documented. The cycles were well tolerated; no delayed
      engraftment in group B was observed. One patient in group A and two patients in
      group B are still in CCR, respectively 47, 42 and 15 months after ABMT. Our rIL-2
      regimen; pre- and/or post-ABMT, was safely tolerated and induced significant
      immunomodulatory effects in pediatric patients

PMID- 8733690
TI  - Feasibility and timing of unrelated donor identification for patients with ALL.
AB  - Patients with relapsed ALL frequently have short duration second or later
      remissions, leaving only a brief window of time when it is possible to perform
      BMT. When no sibling donor is available, identifying and unrelated donor in a
      timely fashion can be difficult while autologous BMT (ABMT) can be performed more
      quickly. We have studied the outcome of 115 consecutive referrals of patients
      with ALL to the University of Minnesota for BMT between September 1991 and August
      1993 to determine the feasibility of URD identification and BMT in these
      patients. In 40 cases (35%) a related allogeneic donor was identified and 30 of
      these patients received BMT at Minnesota. Our policy for patients with no related
      donor (n = 75) was to initiate an unrelated donor (URD) search and seek insurance
      authorization for both URD and ABMT immediately on referral; URD BMT is offered
      if a donor is available within 4 months. Thereafter ABMT is offered if an URD is
      no yet available. Fifty-eight patients (50% of referrals) initiated an URD
      search. An URD was identified for 22 patients (37%) of searches) and 15 patients
      (13% of referred patients) received URD BMT. The median time from patient
      referral to donor identification was 10 weeks. Nineteen percent of referred
      patients died prior to transplant despite all efforts to expedite BMT. Further
      efforts are needed to speed the process of donor selection for patients with ALL.
      Clinical risk factors (eg leukocyte count, cytogenetics), patient age and donor
      histocompatibility need to be integrated for proper patient counseling and
      therapeutic choices.

PMID- 8733691
TI  - Cure of X-linked lymphoproliferative disease (XLP) with allogeneic hematopoietic
      stem cell transplantation (HSCT): report from the XLP registry.
AB  - Seven male patients in the David T Purtilo International X-linked
      Lymphoproliferative Disease (XLP) Registry have undergone allogeneic
      hematopoietic stem cell transplantation (HSCT). All patients received HSCT from
      HLA-identical donors: sibling BM, five; unrelated BM, one; and sibling umbilical
      cord blood, one. Ages at time of HSCT ranged from 5 to 30 years. Pre-HSCT
      clinical course varied, but four boys had a significant history of chronic and/or
      serious infections. Conditioning regimens varied: TBI containing regimens, four,
      chemotherapy only, three. All patients engrafted. Six developed grade I-II acute
      GVHD but no chronic GVHD. Four are alive and well with normal immune function
      greater than 3 years following HSCT. Three died within 100 days: disseminated
      adenovirus, one; polymicrobial sepsis, one; and multiple organ system failure and
      bleeding diathesis, one. No EBV-associated post-transplant complications were
      observed, even though all donors except the umbilical cord blood were EBV
      seropositive. Unsuccessful HSCT was associated with age at HSCT (> 15 years), TBI
      containing regimen and significant history for pre-HSCT infections. These results
      provide evidence that HSCT performed during childhood with HLA-identical sibling
      donors, regardless of EBV serostatus, offers the only curative therapy for XLP.

PMID- 8733692
TI  - Treatment of patients with myelodysplastic syndromes with allogeneic bone marrow
      transplantation from genotypically HLA-identical sibling and alternative donors.
AB  - Between December 1981 and March 1994, 24 patients with a myelodysplastic syndrome
      (MDS) underwent allogeneic bone marrow transplantation (BMT) for RA with
      trilineage dysplasia (n = 4), CMML (n = 1), RAEB (n = 4), RAEBt (n = 9) and AML
      following MDS (n = 6). Fifteen patients (two RAEB, seven RAEBt and six sAML)
      received chemotherapy before BMT resulting in complete remission in 10 patients
      (six RAEBt and four sAML) at the time of BMT. Sixteen marrow donors were
      genotypically HLA-identical siblings. Remaining donors were other family members
      (five) or unrelated donors (three). The status of the underlying disease at the
      time of conditioning was the major factor determining long-term survival. The
      disease-freed survival of RA patients and patients presenting with RAEB, RAEBt
      and AML but transplanted in complete remission, was respectively 50 and 60%. On
      the contrary, none of the nine high-risk MDS patients transplanted with
      persistent disease, survived. Outcome after transplantation with alternative
      donors was inferior with one long-term survivor, mainly related to the high
      incidence of severe acute GVHD and its accompanying infectious complications. Six
      patients relapsed resulting in an actuarial probability of relapse of 28%. Twelve
      patients died of transplant-related complications leading to a non-relapse
      mortality at 5 years of 50%. At present eight patients are alive and disease-free
      20 to 132 months post-transplantation resulting in an actuarial 5-year disease
      free survival of 40.7%. Our results suggest that allogeneic bone marrow
      transplantation is a feasible treatment option for patients with MDS. However,
      improvement in GVHD prophylaxis and supportive care to reduce transplant-treated
      mortality and improved relapse prevention are imperative.

PMID- 8733693
TI  - Serum HLA class I antigen levels in allogeneic bone marrow transplantation: a
      possible marker of acute GVHD.
AB  - The levels of serum HLA class I antigens were determined at weekly intervals up
      to 5 weeks in 46 patients who had undergone allogeneic BMT. In patients with GVHD
      grade I or with GVHD grade I and fever of unknown origin (FUO), serum HLA class I
      antigen levels did not change during the observation period. In patients with
      GVHD grade II-IV serum HLA class I antigen level significantly increased in the
      week before the onset of GVHD, was maximal at the onset of GVHD and then
      persisted unchanged in the following 2 weeks. In patients with GVHD grade I or
      GVHD grade II-IV and infections whose onset coincided with that of acute GVHD a
      significant increase of serum HLA class I antigen level was found 2 weeks after
      the onset of the infectious episode. An increase of serum HLA class I antigen
      level was also found before the onset of repetitive GVHD grade II-IV episodes as
      well as during and after infectious episodes whose onset occurred after the onset
      of acute GVHD. The mean +/- s.d. concentrations of serum HLA class I antigens
      during GVHD grade II-IV episodes (9.4 +/- 3.4 micrograms/ml) and 2 weeks after
      the onset of infectious episodes (7.1 +/- 1.6 micrograms/ml) are significantly (P
      < 0.01 and P < 0.05, respectively) higher than that found 2 weeks before the
      onset of GVHD (3.0 +/- 0.5 micrograms/ml). The results of the present
      investigation suggest that measurement of serum HLA class I antigen level may be
      a possible marker to detect an acute GVHD following BMT.

PMID- 8733694
TI  - Feasibility and toxicity of interferon maintenance therapy after allogeneic BMT
      for multiple myeloma: a pilot study of the EBMT.
AB  - A pilot study was undertaken in order to determine the feasibility and toxicity
      of rh-alpha-2b-interferon as maintenance therapy after allogeneic BMT for
      multiple myeloma. The study incorporated planned dose escalation of interferon in
      successive patient cohorts from an initial dose of 1 MU three times weekly to a
      target dose of 3 MU three times weekly. No clinical complications were observed
      in five patients receiving a dose of 1 Mu three times weekly. At a dose of 2 MU
      three times weekly, one of seven patients developed acute GVHD, which was fatal.
      At a dose of 3 MU three times weekly, four of five patients developed acute or
      chronic GVHD, and the study was therefore terminated at this point. We conclude
      that the use of interferon in myeloma patients early after allogeneic BMT is
      associated with a significant risk of GVHD, which is dose-related, and that the
      maximum tolerated dose in the early post-transplant period is 1-2 MU three times
      weekly.

PMID- 8733695
TI  - Relapsed acute lymphoblastic leukemia: similar outcomes for autologous and
      allogeneic marrow transplantation in selected children.
AB  - The therapy of choice for relapsed childhood acute lymphoblastic leukemia is
      controversial. We retrospectively compared the outcome of 57 patients who
      received autologous bone marrow transplantation (BMT) with 17 patients who
      underwent allogeneic BMT for B cell lineage acute lymphoblastic leukemia after at
      least one marrow relapse. The allogeneic BMT cohort included only those who would
      also have been eligible for autologous BMT had they not had a matched sibling
      donor. Specifically, patients who were not in complete remission, those with T
      cell positive leukemia, t(9;22) or those with only an extramedullary relapse were
      excluded from both groups. Conditioning regimens included total body irradiation
      and chemotherapy. Age, white blood count at diagnosis, and duration of first and
      longest complete remissions were comparable for the two groups. The median follow
      up of the event-free survivors was 4.8 years for those who received an autologous
      BMT (n = 26) and 4.6 years for those who received an allogeneic BMT (n = 8). The
      relapse rate was higher in the autologous BMT group and the incidence of non
      leukemic deaths higher in the allogeneic BMT group. Event-free survival at 3
      years was comparable for the two groups (47% +/- 7 vs 53% +/- 12, autologous vs
      allogeneic, respectively; P = 0.77). Based upon these findings, we concluded that
      the outcome for autologous BMT was equivalent to allogeneic BMT for relapsed
      childhood B cell lineage acute lymphoblastic leukemia in selected clinical
      situations.

PMID- 8733696
TI  - High-dose busulfan and cyclophosphamide followed by autologous transplantation in
      patients with advanced breast cancer.
AB  - This study was conducted to evaluate the efficacy of high-dose busulfan (BU) and
      cyclophosphamide (CY) in patients undergoing autologous hematopoietic stem cell
      transplantation for metastatic breast cancer. Twenty-two patients with stage IV
      breast cancer underwent autologous marrow (n = 13), peripheral blood stem cell
      (PBSC) (n = 6) or marrow plus PBSC (n = 3) transplantation following BU (14-16
      mg/kg) and CY (120-180 mg/kg). Of 22 patients, 18 had refractory relapse, one had
      primary refractory disease, two had responding relapse and one had no evidence of
      disease (NED) at the time of transplant. Eight patients had bone only disease,
      six had bone plus visceral disease, and eight had loco-regional recurrent
      disease. The median time for diagnosis to transplant was 1124 days (range 210
      2582). Staging for evaluation of response was performed 4-6 months after
      transplantation. Six patients were not evaluable (NE) for response because of NED
      at transplant (n = 1) or early death due to transplant-related complications (n =
      5) (one of RSV interstitial pneumonia, two of fungal infection and two of regimen
      related toxicities) occurring at a median of 17 days (range 14-59) post
      transplant. The patient who was NED at time of transplant is still NED on day 336
      post-transplant. Seven of the 16 evaluable patients achieved a complete response
      (CR) (44%), five achieved a partial response (PR) (31%) and five had no response
      (NR), with an overall response rate of 75%. Five of 18 (28%) patients treated in
      refractory relapse, and both patients treated in responding relapse achieved a
      CR. Of the seven patients who achieved CR, three are alive and disease-free on
      days 204, 276 and 752 and three relapsed on days 209, 715 and 1127 post
      transplant. One patient in CR died of aspergillus pneumonia on day 306 post
      transplant. The median day to progression in five patients who achieved a PR
      after transplantation was 335 (range 144-507). The probabilities of survival and
      event-free survival (EFS) at 2 years was 0.22 and 0.15, respectively for all 22
      patients. The probability of EFS at 2 years for the eight patients achieving CR
      (including one patient who was NED at transplant) was 0.33. The probabilities of
      overall survival at 2 years in patients who did and did not achieve a CR after
      transplantation was 0.63 and 0.14, respectively (P = 0.004). These data suggest
      that high-dose BU-CY followed by autologous stem cell transplantation is an
      effective regimen in patients with advanced breast cancer demonstrating that BU
      is an active agent in this disease and could be incorporated into treatment
      regimens requiring hematopoietic stem cell support.

PMID- 8733697
TI  - Results with high-dose chemotherapy and unpurged autologous stem cell
      transplantation in 73 patients with chronic myelogenous leukemia: the MD Anderson
      experience.
AB  - The purpose of this study was to evaluate the effectiveness of unpurged
      autologous stem cell transplantation (ASCT) for chronic myelogenous leukemia
      (CML) and its impact on the survival of patients in first and late chronic phase
      (CML-CP) including those resistant to or unable to tolerate interferon alfa (IFN
      alpha) therapy. Between 1982 and 1993, 73 patients with CML who underwent ASCT
      were evaluated. Twenty-eight patients had signs of transformation, 20 were in
      second or subsequent CP, 22 had CML-CP and had shown resistance to or were unable
      to tolerate IFN-alpha therapy, and there had Philadelphia (Ph) chromosome
      negative CML. Survival of patients in CML-CP who underwent ASCT was compared to
      controls who were in first CP receiving INF-a therapy. Patients and controls were
      matched for age, decade of therapy, response to IFN-alpha therapy (resistance vs
      toxicity) and the time to ASCT (study group) vs time to resistance (control
      group). Nine 12% patients failed to achieve hematologic recovery, and five (7%)
      had early death secondary to toxicity. Twenty-seven (58%) patients who received
      transplants in advanced-stage CML and 18 (82%) transplanted in CML-CP achieved
      complete hematologic remission (CHR). The incidence of complete cytogenetic
      response was 10 and 14%, respectively. The median survival of these two groups of
      patients was 5 and 34 months, respectively (P < 0.001). However, the survival of
      patients in CML-CP was not significantly different from controls (34 vs 49
      months; P = 0.17). We conclude that unpurged ASCT does not prolong the survival
      of patients in CML-CP who are resistant to IFN-alpha therapy. Progress in
      autotransplantation in CML might require innovative approaches to eradicate the
      leukemic cells from the autologous stem cells prior to transplants.

PMID- 8733698
TI  - Follow-up of leucocyte and reticulocyte counts for the prediction of early graft
      failure after non-HLA-identical BMT in children.
AB  - Allogeneic BMT using a non-genotypically HLA-identical donor may be curative for
      children suffering from lethal haematological diseases, who lack a genotypically
      HLA-identical donor. Unfortunately, graft failures are often seen, especially
      after T cell depletion of the graft. We studied whether untimely decreased counts
      of leucocytes and reticulocytes in peripheral blood might predict graft failure
      at an early stage. Fifty-five recipients of a non-genotypically HLA-identical BM
      graft were included in the study; data from these children were compared with
      those of 77 recipients of a genotypically HLA-identical BM graft. Time-related
      reference values of peripheral blood leucocyte and reticulocyte counts were
      established in graft recipients with proven donor-origin recovery after BMT.
      Graft failure after nonHLA-identical BMT was observed in 16 out of 55 children
      (29%) and after HLA-identical BMT in one out of 77 (1.3%). With respect to early
      graft failure, the predictive value of granulocyte numbers falling below the
      lower limit of the reference values and a rapid decline of reticulocyte numbers
      after their appearance in peripheral blood was 100% (95% confidence intervals of
      83-100% and of 80-100%, respectively). Early immunosuppressive intervention was
      applied in six patients and was successful in three of them.

PMID- 8733699
TI  - Effect of deoxyspergualin on graft-versus-host disease and graft- versus-leukemia
      in mice.
AB  - The effect of 15-deoxyspergualin (DSG) on bone marrow (BM) engraftment and graft
      versus-host disease (GVHD) was studied in mice across both major (MHC) and minor
      (MiHC) histocompatibility barriers. (BALB/c x C57BL/6)F1 mice were inoculated
      with C57BL/6 cells, CBA mice were given B10.BR cells and BALB/c mice were
      transplanted with B10.D2 cells. All recipient mice were irradiated lethally or
      sublethally prior to transplantation. DSG had no effect on engraftment of
      parental cells in F1 mice at both 2.5 mg/kg and 10 mg/kg given daily for 10 days
      after treatment. Survival of F1 recipients of C57BL/6 cells increased
      significantly with 2.5 mg/kg DSG (p < 0.05). Across MiHC, 75% of DSG-treated CBA
      mice survived transplant for more than 150 days. No effect on GVHD was observed
      in the B10.D2 --> BALB/c setting. DSG abolished graft-versus-leukemia (GVL)
      effects in F1 mice transplanted with both BM and spleen cells (20%) of C57BL/6
      mice and additionally inoculated with B cell leukemia (BCL1). In summary, in the
      semi-allogeneic murine models presented here DSG prevented GVHD but at the same
      time suppressed GVL effects induced by the allograft. For clinical use, DSG might
      therefore be very useful for prevention of GVHD post-allogeneic bone marrow
      transplantation for non-malignant diseases or for leukemia.

PMID- 8733700
TI  - Specific depletion of alloreactivity against haplotype mismatched related
      individuals by a recombinant immunotoxin: a new approach to graft-versus-host
      disease prophylaxis in haploidentical bone marrow transplantation.
AB  - Haploidentical bone marrow transplantation (BMT) is associated with a high risk
      of severe graft-versus-host disease (GVHD). While pan-T cell depletion of the
      graft is the most effective means of preventing severe GVHD, it is associated
      with delayed recovery of T cell function leading to fatal infections. We used two
      related Pseudomonas exotoxin-based immunotoxins, anti-Tac(Fv)-PE38 and anti
      Tac(Fv)-PE38KDEL, that both target the IL-2 receptor on activated T cells, to
      specifically deplete alloreactive lymphocytes against haploidentical stimulators.
      The functional capacity of the remaining lymphocytes was tested in proliferative
      assays against the original haploidentical stimulator and pooled cells from other
      mismatched donors (third party). We varied the recombinant toxin concentration
      and schedule to determine the optimum conditions for selective depletion. In 10
      experiments, the mean residual reactivity after depletion was 7.6 +/- 1.4%
      against the haploidentical stimulator and 64.2 +/- 5% against the third party,
      expressed as a percentage of the undepleted response to the same stimulators.
      Depletion was shown to be specific for mixed lymphocyte culture (MLC)-activated
      lymphocytes. The immunotoxin did not affect CFU-GM growth of normal BM cells.
      This selective depletion of haploidentical alloreactivity could be used to
      prevent GVHD while conserving immune recovery following haploidentical BMT.

PMID- 8733701
TI  - Granulocytic sarcoma after allogeneic bone marrow transplantation: a
      retrospective European multicenter survey. Acute and Chronic Leukemia Working
      Parties of the European Group for Blood and Marrow Transplantation.
AB  - In a retrospective analysis we assessed occurrence, contributing factors and
      outcome of patients experiencing granulocytic sarcoma as a localized
      extramedullary relapse after allogeneic BMT. EBMT members were asked to report
      the number of patients transplanted for leukemia between January 1981 and
      December 1992 and the number of patients with granulocytic sarcoma. Of a total of
      5824 patients transplanted for AML, CML or MDS by 86 teams, granulocytic sarcoma
      was observed in 26 patients (0.45% occurring 4-56 months after BMT. Granulocytic
      sarcoma occurred after allogeneic BMT in 20 out of 3071 patients grafted for AML
      (0.65%), and in the CML/MDS subgroup in six out of 2753 grafted patients (0.22%).
      Granulocytic sarcoma can involve any site of the body, presenting as a soft
      tissue mass; it occurred in body cavities (eg pleural cavity, abdominal cavity,
      spinal canal, stomach and bladder), the head and neck region (orbit, ear, skull
      base, peripheral nerves), the trunk and limbs, and mammary and sex glands.
      Granulocytic sarcoma predicts an additional hazard to outcome after BMT. Nine of
      26 patients (33%) were alive 15-151 months after the onset of granulocytic
      sarcoma. Advanced disease stage at grafting adversely affected survival and all
      patients died. The best treatment option still needs to be defined.

PMID- 8733702
TI  - Misoprostol prophylaxis for high-dose chemotherapy-induced mucositis: a
      randomized double-blind study.
AB  - From April 1993 to September 1993, 15 patients with lymphoid or solid neoplasms
      underwent 16 non-cryopreserved peripheral stem cell transplantation courses using
      the ICE (ifosfamide, carboplatin, etoposide) program. They were randomized in a
      double-blind clinical trial to received oral misoprostol or placebo for mucositis
      prophylaxis. The active drug or placebo administration began jointly with
      chemotherapy at day -4 and was continued until day 16. The mucositis incidence
      and severity was significantly higher in patients who received misoprostol. We
      found no differences regarding myelosuppression, infections or other chemotherapy
      complications. Our results do not support the use of oral misoprostol as
      administered in this study, for high-dose chemotherapy-induced mucositis
      prophylaxis.

PMID- 8733703
TI  - European survey of herpesvirus resistance to antiviral drugs in bone marrow
      transplant recipients. Infectious Diseases Working Party of the European Group
      for Blood and Marrow Transplantation (EBMT).
AB  - A survey of herpesvirus resistance to antiviral drugs was conducted by mailing a
      questionnaire to the centers of the European Group for Blood and Marrow
      Transplantation (EBMT). Results from 68 centers were reported. The number of
      centers with proven or suspected resistance of herpes simplex virus (HSV) was 17
      (25%), of varicella-zoster virus (VZV) was three (4%), and of cytomegalovirus
      (CMV) was 19 (28%). Acyclovir-resistant HSV strains were recovered from 10
      patients with HSV disease. Replacement of acyclovir by foscarnet in seven of
      these patients resulted in improved or healed HSV disease in five (17%).
      Acyclovir-resistant VZV was isolated from one patient with zoster which improved
      after a change to vidarabine therapy. CMV resistance to ganciclovir was proven in
      only two patients but was suspected in 23. Ganciclovir was replaced by foscarnet
      in 15 of these 25 patients which resulted in better virological and/or clinical
      outcome in 13 (87%). These results suggest that herpesvirus resistance is an
      emerging problem in marrow transplant recipients, and that foscarnet treatment
      may prove to be a valuable alternative when the presence of acyclovir- or
      ganciclovir-resistant herpesvirus disease is documented in these patients.

PMID- 8733704
TI  - Campath-1G in vivo confers a low incidence of graft-versus-host disease
      associated with a high incidence of mixed chimaerism after bone marrow
      transplantation for severe aplastic anaemia using HLA-identical sibling donors.
AB  - We have evaluated the effect of in vivo Campath-1G on engraftment and GVHD in 23
      patients with severe aplastic anaemia transplanted from HLA-identical sibling
      donors. In 14 patients Campath 1g was given pre-transplant for up to 9 days in an
      attempt to overcome graft rejection (group 1). In nine patients Campath-1G was
      given pre-transplant, but also continued post-transplant until day +5 to reduce
      GVHD (group 2). There were three patients with late graft failure in group I
      following initial neutrophil engraftment, and four cases of grade II+ GVHD. In
      group II, two patients had early graft failure (no take), and there were no cases
      of acute GVHD out of seven evaluable patients. One patient in group I developed
      chronic GVHD of the liver, and two patients (one in each group) had transient
      localised chronic GVHD. PCR of short tandem repeats was used to evaluate
      chimaeric status in 13 patients. Of 11 patients with initial neutrophil
      engraftment, only one had 100% donor haemopoiesis at all times. The remaining
      patients had either transient mixed chimaerism or persistence of recipient (<
      20%) cells. We conclude that in vivo Campath-1G is associated with a high
      incidence of mixed chimaerism which tips the balance away from GVHD but towards
      graft rejection.

PMID- 8733705
TI  - Search for the antigen-specificity of homogeneous IgG components (H-IgG) after
      allogeneic bone marrow transplantation.
AB  - After allogeneic BMT, transient homogeneous Ig components (H-Ig) can be detected
      in the sera of most graft recipients. So far, data on the antigen-specificity and
      therefore the function of these H-Ig are not available. Such information may be
      important for our understanding of the underlying mechanisms that are responsible
      for these excessive clonal B cell expansions, and it may help to delineate the
      functional antibody repertoire after BMT. In the present study, sera of 98
      paediatric BM graft recipients were investigated for the potential presence of H
      Ig of IgG isotype (H-IgG) with specificity towards a panel of antigens, including
      vaccine and herpes virus antigens, auto-antigens and allo-antigens. The vast
      majority of H-IgG in sera of BM graft recipients were unreactive when tested for
      this panel of antigens. However, in four cases, antigen-specificity of H-IgG to
      tetanus toxoid could be demonstrated after vaccination with that antigen. An
      explanation for the negative findings may be either that a restricted antibody
      production had been elicited by other non-tested antigens, eg substances of
      colonizing and translocating bacteria or of food antigens, or that the H-IgG
      components may have anti-idiotype or anti-'self' specificity.

PMID- 8733706
TI  - TCR-beta transgenic mice fail to mediate a GVHR due to defects of allorecognition
      and subsequent IL-2 generation.
AB  - All T cells of TCR-beta transgenic mice bear a single TCR-beta chain and
      consequently the diversity of the TCR may be reduced by as much as one million
      fold. Despite this limited diversity, many measures of lymphocyte function in
      these mice are normal. We have previously demonstrated that lymphoid cells from
      TCR-beta mice are unable to mediate an intense graft-versus-host response (GVHR).
      In order to investigate the mechanism of this hyporesponsiveness, we studied in
      vivo allorecognition in diverse strains of TCR-beta mice. All tested strains of
      TCR-beta mice failed to mediate a substantial GVHR across multiple H-2 barriers.
      In addition, mixtures of cells from several strains of TCR-beta mice only
      generated mild GVHRs. Sensitive tests of in vitro allorecognition show that
      lymphoid cells from TCR-beta mice respond less vigorously to alloantigen as
      measured both by decreased proliferation and decreased IL-2 production in a MLR.
      In addition, cells from TCR-beta mice fail to use exogenous IL-2 appropriately in
      their response to alloantigen. We conclude that the fixed TCR-beta chain causes a
      defective response to alloantigen, which is measured as decreased IL-2 generation
      and utilization, and that this abnormality results in a decreased GVHR.

PMID- 8733707
TI  - Psychological stress symptoms before and after autologous bone marrow
      transplantation in patients with solid tumors.
AB  - This study sought to examine patterns of changes of psychological stress symptoms
      in autologous bone marrow transplantation (ABMT) recipients. Forty-nine patients
      affected by solid tumors were assessed using the Symptom Questionnaire on
      admission to hospital (before high-dose chemotherapy and ABMT) and before
      discharge. Symptoms of anxiety and anger tended to decrease and relaxation of
      improve over time. Nevertheless, on admission to hospital 30-50% of the patients
      reported severe to moderate symptoms of anxiety and depression. Before discharge,
      the prevalence was still high (20-35%). The implications of these findings are
      discussed in terms of the need to monitor the evolution of emotional functioning
      of cancer patients undergoing ABMT.

PMID- 8733708
TI  - External quality assurance for CD34 cell enumeration--results of a preliminary
      national trial. Royal Microscopical Society Clinical Flow Cytometry Group QA
      Schemes.
AB  - With the development of haematopoietic stem cell (HSC) mobilisation strategies
      and the associated technical expertise in leukapheresis has come the need for
      accurate and reproducible enumeration of HSC in the peripheral blood. Enumeration
      of HSC is not only required for timing of the harvest but is valuable in
      determining that the minimum number of HSC required for successful engraftment
      has been collected. In order to establish a minimum number of HSC required,
      results from multiple institutions performing such transplants need to be
      assessed. Clearly, to compare results from multiple centres requires confidence
      in the reproducibility of the assay. We have evaluated an established EQAS method
      which has already been proven in the external quality assurance of CD4
      measurement in clinical samples to assess the inter- and intra-laboratory
      reproducibility of CD34 measurement. Fifteen laboratories participated in two
      distributions in which 28 samples were analysed. Standardised methods were not
      employed, laboratories using their routine methods. Participants reported their
      results in terms of '% positive of total leukocytes' and 'absolute number of
      CD34+/microliters'. A wide range of clinical samples was despatched and analysed
      with CD34 cell content ranging from 0.08-19.31% positive. The coefficients of
      variance (CV) associated with the estimations of relative proportions and
      absolute numbers were maximally 100.1 and 136.6%, respectively. This study
      highlights the need for external quality assurance and standardisation of the
      methodology of this assay.

PMID- 8733709
TI  - Rapid detection cytomegalovirus pneumonia in recipients of bone marrow
      transplant: evaluation and comparison of five survey methods for bronchoalveolar
      lavage fluid.
AB  - To detect cytomegalovirus-associated interstitial pneumonia (CMV-IP) in
      recipients of BMT in its earliest stage, five CMV methods were assessed for their
      usefulness using bronchoalveolar lavage fluid as the test specimen. Of the 43
      cases enrolled in the study, PCR was positive in 12 cases, shell vial in eight,
      culture in eight and cytology in three. There were no positive cases in in situ
      hybridization. Based on this result, the 43 cases were classified into four
      groups: Group 1, three cases: positive in PCR, shell vial and cytology; Group 2,
      five cases: positive in PCR and shell vial; Group 3, four cases: positive only in
      PCR; and Group 4, 31 cases: negative in all CMV tests. Cases in Group 1 were
      judged as having the highest risk of overt CMV-IP. They were successfully treated
      with a combination of ganciclovir and immunoglobulin. Group 2 was diagnosed as
      having active CMV infection and ganciclovir monotherapy was effective for these
      patients. Groups 3 and 4 were not given anti-CMV therapy, but they were free from
      CMV-related manifestations throughout the study. The sensitivity and specificity
      of each survey method for the detection of Groups 1 and 2 were 1.0 and 0.89 in
      PCR, 1.0 and 1.0 in shell vial, 0.88 and 1.0 in culture, and 0.38 and 1.0 in
      cytology. Similarly, the positive and negative predictive values were 0.67 and
      1.0 in PCR, 1.0 and 1.0 in shell vial, 1.0 and 0.97 in culture, and 1.0 and 0.88
      in cytology. Thus, CMV survey on bronchoalveolar fluid was thought to be useful
      in detecting post BMT CMV-IP in its earliest stage.

PMID- 8733710
TI  - Monitoring of CMV infection: a comparison of PCR from whole blood, plasma-PCR,
      pp65-antigenemia and virus culture in patients after bone marrow transplantation.
AB  - Rapid, specific and sensitive methods are essential for early detection of CMV
      infection in patients after marrow transplantation. Thus, in a prospective study,
      PCR from whole blood, plasma-PCR, pp65-antigenemia and virus culture were used
      and compared in 20 consecutive marrow transplant recipients for early diagnosis
      of CMV infection and monitoring of antiviral therapy. Moreover, semi
      quantification of the viral load in blood samples by PCR from whole blood or
      plasma and pp65-antigenemia was performed. Fifteen out of 20 patients were found
      to be CMV positive by PCR from whole blood, plasma-PCR and pp65-antigenemia,
      whereas only 9/20 developed culture-proven viremia and/or viruria. PCR from whole
      blood, plasma-PCR and pp65-antigenemia revealed identical results in 96 and
      discordant results in 13 of 109 blood samples (P < 0.01). The efficacy of
      antiviral therapy was monitored by semi-quantitative scoring of pp65-antigen
      positive leukocytes and/or CMV-DNA levels in blood and plasma samples. Twelve of
      13 patients were found to be CMV negative by all methods after 14 days of
      ganciclovir therapy. A good correlation of the semi-quantitative evaluation of
      the three assays was demonstrated. Thus, all three highly sensitive assays seem
      to be suitable for screening patients at risk for CMV infection and monitoring
      the efficacy of antiviral therapy.

PMID- 8733711
TI  - Vasculitis post-autologous transplant causing pulmonary shadows in a patient with
      Hodgkin's disease.
AB  - A 29-year-old male was treated for recurrent Hodgkin's disease with autologous
      bone marrow and peripheral blood stem cell transplantation. CT scanning shortly
      after transplantation showed widespread infiltrates, which appeared to be
      malignant at thorocoscopy but which biopsy showed to be vasculitis. A prolonged
      reducing dose of steroids has successfully controlled the vasculitis and his
      current CT scan of lung has no shadows. The cause of his vasculitis is unclear
      and the case illustrates the importance of tissue diagnosis in possible relapses
      of Hodgkin's disease following high-dose chemotherapy.

PMID- 8733712
TI  - Acute mediastinitis secondary to leakage of parenteral nutrition from a migrated
      central venous catheter in a patient undergoing autologous bone marrow
      transplant.
AB  - We describe an unusual case of pyrexia of unknown origin in a patient undergoing
      autologous bone marrow transplantation for metastatic breast cancer. The fever
      was due to extravasation of lipid-containing hyperalimentation fluid from a
      migrated central venous catheter into the mediastinum, resulting in mediastinitis
      and pleurisy. The fever persisted despite broad-spectrum antibiotics and
      amphotericin B, and finally responded to steroids.

PMID- 8733713
TI  - Hydronephrosis in children after bone marrow transplantation: case reports.
AB  - Hydronephrosis post-bone marrow transplantation (BMT) diagnosed in five children,
      was caused by hemorrhagic cystitis and blood clots in the bladder, congenital
      uretro-pelvic junction stenosis and ureteral obstruction due to adenoviral
      infection. Patients received conservative therapy to treat the symptoms. However,
      hydronephrosis did not change the outcome of BMT. Therefore, we suggest less
      aggressive procedures to treat children with hydronephrosis.

PMID- 8733714
TI  - Disseminated BCG infection in severe combined immunodeficiency presenting with
      severe anaemia and associated with gross hypersplenism after bone marrow
      transplantation.
AB  - An infant with severe combined immunodeficiency (SCID) is described, who
      presented with severe anaemia and hepatosplenomegaly due to disseminated Bacillus
      Calmette-Guerin (BCG) infection involving the bone marrow, liver and spleen.
      After BMT, huge splenic enlargement occurred, presumably due to proliferation of
      engrafted donor lymphocytes, leading to severe hypersplenism. Peripheral blood
      cell consumption was resolved by splenectomy, but gradual loss of the marrow
      graft followed.

PMID- 8733715
TI  - T cell-depleted allogeneic bone marrow transplantation from a partially HLA
      mismatched unrelated donor for progressive chronic lymphocytic leukemia and
      fludarabine-induced bone marrow failure.
AB  - A 49-year-old man with a 3-year history of chronic lymphocytic leukemia (CLL,
      stage B at diagnosis) responded well to four course of fludarabine, but developed
      marrow failure and prolonged pancytopenia lasting 9 months following the fifth
      course. Fludarabine therapy could not be continued due to pancytopenia,
      eventually resulting in disease progression. Bone marrow transplantation from an
      unrelated donor mismatched at one DRB1 locus and both DQB1 loci was performed as
      salvage therapy. The marrow was depleted of T cells with Campath-1G. Pre
      transplant immunosuppression was enhanced with 600 cGy total lymphoid irradiation
      and Campath-1G infusions in addition to 120 mg/kg cyclophosphamide and 1200 cGy
      fractionated total body irradiation. Cyclosporine alone was used as post
      transplant immunosuppression. Neutrophils reached 0.5x10(9)/1 on day 14 and
      platelets 50 x 10(9)/1 on day 40. No acute graft-versus-host disease was seen.
      Bulk disease detected on CT scanning prior to BMT was found to have disappeared
      10 weeks after BMT. The marrow showed residual disease (5% CD5+/CD19+ cells) 9
      weeks after transplantation, which had decreased markedly at 13 (0.5%) and 26
      (0.4%) weeks. The patient is currently alive and well 10 months after BMT with no
      clinically detectable disease. We conclude that BMT from an unrelated donor is a
      feasible treatment option in advanced CLL.

PMID- 8733716
TI  - Third autologous stem cell transplants for late relapse of multiple myeloma.
AB  - Double autologous bone marrow transplantation (ABMT) has been reported as an
      efficient form of consolidation for patients with multiple myeloma (MM). However,
      few data are available about feasibility and efficacy of a third ASCT in case of
      relapse. Here we report two patients with MM who received a third ASCT for late
      relapse (74 and 52 months) after a double ABMT. Both patients were male with IgG
      gamma MM (stage IIIA according to the Durie Salmon classification). The two
      patients were in PR > 50% after a first-line treatment. A double ABMT was
      performed after relapse and patients remained in PR > 50% after double
      intensification, lasting 71 and 49 months, respectively. The third ASCT was
      performed 7 and 10 months, after second relapse. One patient needed 15 months to
      reach 50 000 platelets, however he did not receive any transfusion after day 14.
      He was in PR > 50%. The other patient was in PR < 50%, 4 months after ABMT with a
      full hematological reconstitution. For patients with late relapse of MM after
      double ABMT, a third ABMT was a feasible treatment and patients seem to remain
      sensitive to high-dose therapy.

PMID- 8733717
TI  - Protein-losing gastropathy associated with cytomegalovirus: a rare and late
      complication of allogeneic bone marrow transplantation.
AB  - A 36-year-old women with chronic myelogenous leukemia in first chronic phase
      received a bone marrow transplant from her HLA-identical brother. The preparatory
      regimen consisted of total body irradiation (10 Gy) and cyclophosphamide (60
      mg/kg for 2 days). Full engraftment was achieved and the woman was monitored as
      an outpatient after discharge from hospital on day 35. One year after BMT, while
      she was on cyclosporin A and steroids because of chronic graft-versus-host
      disease, the patient developed protein-losing gastropathy associated with
      cytomegalovirus infection (with no gastrointestinal symptoms), which regressed
      spontaneously in 4 weeks.

PMID- 8733718
TI  - Haploidentical cord blood transplant contaminated with maternal T cells in a
      patient with advanced leukaemia.
AB  - Myeloablative treatment followed by lymphohaematopoietic reconstitution with stem
      cells from umbilical cord blood (UCB) can cure children with leukaemia. The
      clinical experience of UCB transplantation with HLA 2- and 3-antigen mismatched
      siblings is rather limited and there are no reports of such patient being given
      UCB significantly contaminated with maternal T lymphocytes. In this study, we
      report our experience in treating a child with chronic myeloid leukaemia in blast
      crisis who was transplanted using UCB cells from mismatched sibling donor
      containing a significant number of maternal T cells. The patient received 1.17 x
      10(8) nucleated cells/kg after conditioning with Ara-C, busulphan, TBI and
      cyclophosphamide. GVHD prophylaxis was with cyclosporine and an anti-CD25
      monoclonal antibody. Although engraftment was somewhat slow it was complete as
      documented by cytogenetic analysis and DNA studies. Results of minimal residual
      disease monitoring by RT-PCR for the hybrid BCR/ABL gene showed no evidence of
      leukaemic mRNA post-transplant. Acute GVHD, skin only, developed on day +14 but
      promptly responded to low-dose steroids. The technique used for UCB collection
      may have cell contamination found. In spite of these potential disadvantages:
      advanced disease, HLA antigen disparate donor and significant maternal T cell
      contamination, the transplant was successful and at a follow-up of 14 months the
      child is well with no evidence of chronic GVHD. Immune naivety of cord blood and
      lack of immunological reactivity of maternal T cells in this context may have
      played a significant role in the outcome of this case.

PMID- 8733719
TI  - Hemolytic uremic syndrome after autologous BMT without TBI.

PMID- 8733720
TI  - The role of plasma exchange for TTP/HUS post-bone marrow transplant.

PMID- 8733721
TI  - Incidence of relapse following blood stem cell transplantation for acute myeloid
      leukemia in first remission.

PMID- 8733722
TI  - Spermine blocks synaptic transmission mediated by Ca(2+)-permeable AMPA
      receptors.
AB  - AMPA-gated glutamate receptors with outward rectification (type I receptors) are
      almost impermeable to Ca2+, while those with strong inward rectification (type II
      receptors) have high Ca2+ permeability. In the present study current responses in
      rat hippocampal neurones mediated by type II AMPA receptors were blocked by
      application of spermine to the external solution (IC50 = 170 microM), but those
      mediated by type I AMPA receptors were not affected. Furthermore, in putative non
      pyramidal neurones in rat hippocampal slices, EPSCs mediated by type II AMPA
      receptors were markedly reduced by 1mM spermine, while those mediated by type I
      AMPA receptors were much less affected. Thus, external spermine exerts
      differential blocking action on the two different types of AMPA receptors.

PMID- 8733723
TI  - Reduced ageing effects of striatal neuronal discharge rate by aged ventral
      mesencephalic grafts.
AB  - Long-term survival of fetal ventral mesencephalic grafts implanted into dopamine
      depleted rats was studied. There was a reduction in apomorphine-induced
      rotations, which reached a maximum 3 months post-grafting. Striatal neuronal
      discharge rate was increased on the intact side of the aged grafted animals when
      compared with young adult striatum. Ipsilateral to the lesion, proximal to the
      graft, where the dopamine nerve terminal density was high but still much lower
      than that seen on the intact side, the firing rate was significantly lower than
      that measured in the intact side of the aged host. In conclusion, the increased
      firing rate seen in striatum after dopamine depletion is normalized by ventral
      mesencephalic grafts and does not show the age-related increase seen in 2-year
      old rats.

PMID- 8733724
TI  - CNTF exerts opposite effects on in vitro development of rat and chick
      photoreceptors.
AB  - Effects of ciliary neurotrophic factor (CNTF) on photoreceptor development in
      dissociated cultures of embryonic chick and newborn rat retina were studied using
      opsin immunoreactivity to characterize photoreceptor differentiation. In the
      presence of CNTF, the number of photoreceptors was increased by up to 200% in
      chick cultures, but was reduced by 82-99% in rat cultures. The EC50 determined
      for CNTF effects in chick and rat cultures were 0.06 ng ml-1 and 0.02 ng ml-1,
      respectively. By studying the time course of in vitro development we showed that
      CNTF transiently stimulated the generation of photoreceptors from opsinnegative
      precursor cells of chick retina, but completely prevented the same process in rat
      cultures. These results suggest that CNTF is involved in the regulation of
      photoreceptor development, but that it can have different actions in the two
      species, at least in vitro.

PMID- 8733725
TI  - Two modes of activity-dependent synaptogenesis of cerebral neurons in vitro.
AB  - Effects of transduction activity and transmission activity on synaptogenesis of
      chick cerebral neurones in dissociated cell culture were studied
      electrophysiologically using two blockers for these activities, tetrodotoxin
      (TTX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively. CNQX
      inhibited the increase of evoked EPSCs more effectively than TTX, whereas both
      blockers similarly reduced the increase of miniature EPSCs (Minis). These data
      indicated that not only transduction-dependent transmission activity but also
      transduction-independent spontaneous activity regulate the synaptic efficiency.
      These two activities are suggested to change the quantal amplitude and the number
      of synaptic sites, respectively.

PMID- 8733726
TI  - Dynamic changes in expression of glutamate transporter mRNAs in developing brain.
AB  - Developmental changes in gene expression for three glutamate transporter subtypes
      in the mouse brain were analysed by in situ hybridization. During embryonic
      stages, GluT-1 and GLT-1 mRNAs were expressed at high levels in the ventricular
      zone, whereas EAAC1 mRNA was not detected in the zone. In the mantle zone,
      transcription levels of three transporter mRNAs were low during embryonic stages,
      and these levels, especially those of the GluT-1 and GLT-1 mRNAs, displayed
      remarkable increases postnatally to reach maximal levels at 14 days of age. These
      dynamic developmental regulations suggest that the glutamate transporter not only
      regulates the excitatory synaptic transmission at mature stages, but might also
      be intimately involved in the brain development.

PMID- 8733727
TI  - Liposome-mediated NGF gene transfection increases ChAT activity in CNS cell
      cultures.
AB  - Liposome-mediated NGF transfection has been shown to increase the expression and
      secretion of NGF in primary rat septo-hippocampal cell cultures. Here we report
      that along with increased NGF expression, the activity of choline
      acetyltransferase, the synthetic enzyme for acetylcholine, is increased by 18%
      within 2 days, by 41% within 4 days and by 32% within 8 days after NGF gene
      transfection in septo-hippocampal cell cultures. This result further confirms
      that biologically active NGF is functionally expressed in septo-hippocampal cells
      when transfected with cDNA for NGF completed with liposomes.

PMID- 8733728
TI  - Striatal NMDAR2B mRNA expression after bilateral cortical and unilateral nigral
      deafferentation.
AB  - We have studies by in situ hybridization histochemistry the regulation of NMDAR2B
      mRNA expression by dopaminergic (DA) and cortical glutamatergic afferent fibres
      in the rat striatum. The effects induced by a unilateral lesion of the medial
      forebrain bundle and a bilateral lesion of the sensorimotor cortex were analysed
      in the dorsal striatum 3 weeks after the lesions. Using a 35S-labelled specific
      oligonucleotide probe no change in NMDAR2B mRNA level was found in DA-depleted
      striatum compared with the normal rat striatum. However, following cortical
      lesions, the levels of NMDAR2B mRNA were significantly increased, specifically in
      the striatal projection area of the SM cortex. These results suggest that NMDAR2B
      mRNA expression is regulated by cortico-striatal fibres in a topographic manner.

PMID- 8733729
TI  - Melatonin receptors activate heteromeric G-protein coupled Kir3 channels.
AB  - The effects of melatonin on circadian pacemaker activity in the central nervous
      system may be the result of melatonin receptor activation of G-protein coupled
      potassium channels which inhibit the action potential firing of neurons. Xenopus
      laevis and human1a melatonin receptors stimulated heteromeric G-protein activated
      inwardly rectifying potassium channels (Kir3.1/Kir3.2) when expressed in vitro in
      oocytes. Pertussis toxin reduced iodo-melatonin (87.1% reduction) and melatonin
      (90.3% reduction) stimulated currents in a time-dependent manner for cells
      expressing X. laevis receptors. A similar pertussis toxin inhibition was observed
      for human melatonin receptors (melatonin, 78.9% reduction). This suggests a
      potential role for heteromeric Kir3 channels in the receptor-mediated actions of
      melatonin in vivo.

PMID- 8733730
TI  - Alzheimer's beta-amyloid peptide is conformationally modified by apolipoprotein E
      in vitro.
AB  - Amyloid beta-peptide (A beta) is a major component of neuritic plaques, a feature
      of Alzheimer's disease (AD) brains. Recently, we showed that A beta adopts two
      major conformational states in solution, which differ in their abilities to form
      amyloid. These are highly amyloidogenic conformer (A beta ac) with a high content
      of beta-sheet and a slowly amyloidogenic conformer (A beta nac) with a random
      coil conformation. Apolipoprotein E (apoE), particularly the E4 isoform, which is
      genetically associated with AD, binds to A beta and modulates fibrillogenesis in
      vitro. In the present work, the influence of apoE on the conformation of A beta
      peptides was studied. The results suggest that, under the conditions used, apoE
      enhances amyloid formation by inducing the conformational transition from A beta
      nac into A beta ac. We propose that an important step in A beta fibrillogenesis
      is the transformation induced by apoE of the soluble non-amyloidogenic into the
      pathological amyloidogenic conformer of A beta.

PMID- 8733731
TI  - Aldose reductase and sorbitol dehydrogenase activities in diabetic brain: in vivo
      kinetic studies using 19F 3-FDG NMR in rats.
AB  - The effects of diabetes mellitus on the kinetic constants of aldose reductase and
      sorbitol dehydrogenase in rat brain were investigated non-invasively in vivo
      using the 3-fluoro-3-deoxy-D-glucose (3-FDG) 19-fluorine (19F) nuclear magnetic
      resonance (NMR) method. While forward flux or both aldose reductase and sorbitol
      dehydrogenase (k1 and k2) were significantly increased, there was no
      corresponding increase in reverse flux (k3 and k4), and leakage of fructose (k5)
      was negligible. These findings indicate that the enzymatic kinetics of aldose
      reductase sorbitol (ARS) in diabetic brain undergo alteration favoring
      intracellular sorbitol and fructose accumulation, the frequently implicated
      biochemical basis of diabetic complications.

PMID- 8733732
TI  - Identification of opioid receptor-like (ORL1) peptide-stimulated [35S]GTP gamma S
      binding in rat brain.
AB  - Recent reports have identified an endogenous peptide ligand for the opioid
      receptor-like (ORL1) receptor. In the present study, ORL1 peptide-stimulated
      [35>]GTP gamma S binding was assessed in rat cortical membranes and brain
      sections to localize ORL1 receptor-activated G-proteins. In membrane assays, with
      20 microM GDP, ORL1 peptide stimulated [35S]GTP gamma S binding by approximately
      two-fold with an ED50 value of 20 nM. ORL1 peptide-stimulated [35S]GTP gamma S
      binding was unaffected by opioid or other G-protein-coupled receptor antagonists.
      In brain sections, ORL1 peptide-stimulated [35S]GTP gamma S binding was
      identified in regions including cortex, amygdala, hypothalamus, thalamus and
      brain stem. The anatomical distribution of ORL1 peptide-stimulated [35S]GTP gamma
      S binding suggests its involvement in cognition, emotion and homeostasis.

PMID- 8733733
TI  - Functional magnetic resonance imaging shows localized brain activation during
      serial transcranial stimulation in man.
AB  - Area and depth penetration of transcranial stimulation methods such as
      transcranial electrical stimulation (TES) are poorly defined. We investigated the
      feasibility of a simultaneous TES and fMRI measurement. The aim was to compare
      the signal intensity changes measured using BOLD fMRI during sequential finger
      movement with the signal response during artificial transcranial stimulation. Tes
      induced contralateral finger contractions and in T2* weighted images a transient
      signal increase was observed in the area underlying the electrodes. Compared with
      the signal obtained during sequential finger movements, the area activated by TES
      was more localized, signal amplitude, was smaller and there was no post-stimulus
      undershoot. These data indicate that TES induces a local blood flow increase
      associated with a drop in the concentration of deoxyhaemoglobin.

PMID- 8733734
TI  - Magnetic imaging in human classical conditioning.
AB  - Magnetoencephalography (MEG) was recorded during aversive classical conditioning
      in an attempt to elucidate the temporal coding of primary somatosensory cortex
      (SI) activation previously found with positron emission tomography. Four healthy
      volunteers participated in the experiment. The reinforced conditioned stimulus
      was displayed on a screen for 2 s, and as it disappeared an unconditioned
      electric shock to the right middle finger followed. A control stimulus, not
      paired with a shock was also presented. With MEG, we observed a conditioned
      magnetic response located in the SI. The conditioned response predated the shock
      presentation and is interpreted as evidence for functional control of nociception
      mediated by corticothalamic projections.

PMID- 8733735
TI  - Utilizing latency for object recognition in real and artificial neural networks.
AB  - A consistent analysis of a visual scene requires the recognition of different
      objects. In vertebrate brains this could be achieved by synchronization of the
      activity of disjunct nerve cell assemblies. During such a process cross-talk
      between spatially adjacent image parts occurs, preventing efficient
      synchronization. Temporal differences, naturally introduced by stimulus latencies
      in every sensory system, were utilized in this study to counteract this effect
      and strongly improve network performance. To this end in our model the image is
      'spread out' in time as a function of contrast-dependent visual latencies, and
      synchronization of cell assemblies occurs without mutual disturbance. The network
      model requires a direct link between visual latencies and the onset of
      synchronous oscillations in cortical cells. This was confirmed experimentally.

PMID- 8733736
TI  - A model for development of Gabor-receptive fields in simple cortical cells.
AB  - A model is proposed for the development of Gabor-like receptive fields of simple
      cells in the visual cortex. We assume that several cortical cells are arranged in
      a ring, with mutual excitatory or inhibitory connections of fixed weight. The
      cells also receive excitatory synapses from LGN; the synaptic weights are
      initially set random and then modified based on correlated dark activity in LGN.
      Each cell finally acquires a simple receptive field best described by a Gabor
      function. Spatial phase in the function varies regularly from 0 to 2 pi with
      rotation along the ring.

PMID- 8733738
TI  - Burst-firing sharpens frequency-tuning in primary auditory cortex.
AB  - Frequency-tuning in 46 high-firing single units from primary auditory cortex of
      ketamine-anaesthetized cats was studied separately for isolated-spike firing and
      burst spike firing. The tuning curve for burst firing was significantly narrower
      than for the overall firing rate condition and, consequently, much narrower than
      for the isolated spikes. The burst firing was found in excess of that predicted
      from a modulated Poisson process, so the results cannot be explained on basis of
      a change in firing rate criterion. We propose that burst firing in auditory
      cortex may selectively enhance frequency tuning dynamically controlled by the
      behavioural state of the animal as well as its stimulus history. Thus burst
      firing may have functional implications for cortical processing.

PMID- 8733737
TI  - Changes in rCBF during grasping in humans examined by PET.
AB  - To identify the functional fields involved in grasping for objects, we measured
      regional cerebral blood flow (rCBF) by positron emission tomography (PET) in
      eight normal volunteers. In the reaching and grasping tasks, the subjects were
      asked to touch or grasp one of five cylinders with their finger(s). Compared with
      reaching, grasping specifically increased the rCBF in the fields located in the
      bilateral premotor area (PMA), the posterior parietal area (PPA) and the
      prefrontal area (PFA). These results indicate that PMA, PPA and PFA might be key
      structures for the performance of grasping movements.

PMID- 8733739
TI  - Activation of cells of cochlear nucleus by electrical stimulation of lateral
      hypothalamus.
AB  - Effects of electrical stimulation of the lateral hypothalamus (HS) were examined
      in 67 cells of the dorsal or ventral cochlear nucleus. Both short latency
      activity in the 10-20 ms post-stimulus period and late activity in the > 20 ms
      post-stimulus period were elicited in response to HS. A greater percentage of
      units exhibited the short latency response in dorsal (89%) than ventral (68%)
      cochlear nucleus. It was not previously recognized that stimulation of the
      hypothalamus could elicit increases in spike activity in this auditory relay
      nucleus. The hypothalamus is known to play a role in visceral-emotional
      functions, including feeding, fleeing, fighting and reproductive behavior. These
      results suggest a means by which neural activities supporting these functions
      could influence acoustic relay transmissions.

PMID- 8733740
TI  - Brain activation during script event processing.
AB  - Regional cerebral blood flow was measured with positron emission tomography in
      seven normal volunteers while they performed various script event verification
      tasks. The left frontal lobe, left anterior cingulate and the anterior part of
      the left superior temporal gyrus were more activated in the script event
      membership and action categorization conditions, whereas the right frontal lobe,
      left superior temporal gyrus and the middle temporal gyrus bilaterally were more
      activated in the script event temporal order verification condition. These
      results indicate that the temporal ordering of script events and determining
      whether an event belongs to a particular script or action category are processed
      by distinctive distributed neuronal networks.

PMID- 8733741
TI  - Similar age-related changes in two regions of muscle with different properties.
AB  - Two regions of the medial gastrocnemius (MG) muscle, with different contractile
      properties and innervated by different nerve branches, were investigated in male
      Sprague-Dawley rats at three ages: 2-3 months, 6-7 months and 24-25 months (i.e.,
      the '50% survival age and beyond': a recommended definition of aged rodents
      derived from lifespan data on a given colony). At the 50% survival age, both
      regions of the MG showed decreased mass, slowed contraction times and a decreased
      number of fast-twitch, but not slow-twitch, muscle fibres. The 40% loss of fast
      twitch muscle fibres was not reflected in the loss of motoneurones, suggesting
      that muscle degeneration precedes motoneurone loss at the 50% survival age in the
      rat.

PMID- 8733742
TI  - Quantitative relations between parietal activation and performance in mental
      rotation.
AB  - The quantitative relationships between functional activation of the superior
      parietal lobule (SPL) and performance in the Shepard-Metzler mental rotation task
      were investigated in 16 human subjects using magnetic resonance (MR) imaging at
      high field (4 Tesla). Subjects were shown pairs of perspective drawings of three
      dimensional objects and asked to judge whether they were the same or mirror
      images. Increased SPL activation was associated with a higher proportion of
      errors in performance. The increase in errors, and the concomitant increase in
      SPL activation, could be due to an increased difficulty in, and therefore
      increased demands for, information processing at several stages involved in
      making a decision, including encoding of the visual images shown, mentally
      rotating them, and judging whether they are the same or mirror images.

PMID- 8733743
TI  - NGF level in the rat sciatic nerve is decreased after long-term consumption of
      ethanol.
AB  - Long-term effects of ethanol consumption on endogenous nerve growth factor (NGF)
      level were investigated in NGF-producing target organs and tissues of the
      peripheral nervous system. Rats were treated with ethanol (20% v/v) for 9 months,
      detoxified for an additional 2 weeks and kept without ethanol for an additional
      month prior to sacrifice. NGF level in the NGF-producing target tissues such as
      iris and submandibular gland and in the trigeminal ganglion and superior cervical
      ganglion, where NGF-responsive perikarya are located, did not differ
      significantly from corresponding controls. In contrast, NGF level in the sciatic
      nerve was significantly reduced by 54%. This indicates that long-term ethanol
      consumption affects retrograde axonal transport of the neurotrophic factor NGF,
      suggesting that NGF deficiency may be part of the pathophysiology of peripheral
      neuropathy due to chronic alcoholism.

PMID- 8733744
TI  - Cortical activation in confrontation naming.
AB  - Functional magnetic resonance imaging was used to detect cortical activation in
      the right and left perisylvian cortex of seven young adult right-handed
      volunteers in response to a letter fluency task and to a visual naming task using
      standardized line drawings. Both letter fluency and visual naming activated left
      dorsolateral prefrontal cortex (Brodmann's areas 6, 9, 44 and 45). Only visual
      naming activated area 37 (a cortical region with strong connections to visual
      association areas), visual association area 19, and areas 39 and 21 previously
      shown to activate with auditory semantic tasks. This study supports a role for
      area 37 as participant in a visual lexicosemantic processing network which may
      otherwise overlap the auditorysemantic network.

PMID- 8733745
TI  - Two different readers in the same brain after a posterior callosal lesion.
AB  - Two different types of reading, one in each hemifield, were exhibited by a
      patient with a lesion of the posterior half of the corpus callosum. The patient
      read normally when words and non-words were presented to his right visual field.
      However, with left visual field presentations, the patient could not read non
      words and vocalized real words very slowly, especially abstract words, inflected
      verbs and function words. He often replaced concrete words by semantic
      associates. Such an abnormal reading pattern is similar to that known as deep
      dyslexia. This unilateral deficit reveals the competence of the right hemisphere
      to initiate some semantic processing and its inability to manage phonological
      coding. The hypothesis that deep dyslexia is due to right hemisphere reading is
      reinforced by the present case.

PMID- 8733746
TI  - Biochemical and pharmacological characterization of cannabinoid binding sites
      using [3H]SR141716A.
AB  - This study describes the binding characteristics of cannabinoid binding sites
      expressed in rat cerebellar membranes using the tritiated derivative of
      SR141716A, the newly described cannabinoid receptor antagonist. A single
      population of high-affinity binding sites (K(D) = 0.59 +/- 0.08 nM; Bmax = 3.86
      +/- 0.42 pmol mg-1 of protein) was demonstrated. Kinetic, competition and
      saturation experiments give similar results in terms of SR141716A affinity. delta
      9-tetrahydrocannabinol and the 11-hydroxy derivative competitively inhibited the
      specific binding of [3H]SR141716A (Ki = 47 +/- 9 and 32 +/- 4 nM, respectively).
      The cannabinoid agonist WIN55212-2 has a 25-fold lower affinity for [3H]SR141716A
      than for [3H]WIN55212-2, showing that the two ligands do not recognize the
      cannabinoid binding site in the same fashion.

PMID- 8733747
TI  - Grasping without form discrimination in a hemianopic field.
AB  - Although patients with blindsight are usually unable to discriminate forms,
      recent neuropsychological data have suggested that they could still use some form
      attributes in object-oriented actions. One patient with a complete right
      hemianopia due to a medial occipital lesion has been tested for his capacities to
      process orientation and size of visual objects. He was presented with either a
      slot of variable orientation or with rectangular objects of the same surface but
      variable length. His performance was studied in three types of tasks: motor, in
      which he had to insert a card in the slot or to grasp the rectangle between thumb
      and indexfinger; verbal, in which forced-choice verbal guesses were required; and
      matching, which required matching orientation or size with wrist or fingers.
      Although responses were at chance level in the two latter conditions, motor
      responses were systematically influenced by both orientation and size of the
      stimulus. These data provide further evidence for two dissociable modes of visual
      information processing dealing respectively with 'what"' the object is vs 'how'
      to grasp it. They also indicate that the neural pathway controlling visuomotor
      transformation in humans is much less dependent on V1 input than the pathway
      involved in visual discrimination and identification.

PMID- 8733748
TI  - Peptidase inhibitors potentiate the effects of neurotensin and neuromedin N on
      self-stimulation of the medial prefrontal cortex.
AB  - The purpose of this study was to examine the possible role of endogenous
      peptidases in the inhibition of intracranial self-stimulation (ICSS) produced by
      injections of neurotensin (NT) and neuromedin N (NN) into the medial prefrontal
      cortex (MPC) of the rat. We studied the effects on ICSS of the MPC of the
      administration of thiorphan and bestatin, two specific inhibitors of the
      peptidases that inactivate NT and NN respectively. Microinjections into MPC of
      thiorphan (10 micrograms) and bestatin (25 micrograms) potentiated in inhibition
      of ICSS produced by the intracortical administration of NT (10 nmol) and NN (20
      nmol) respectively. This potentiation affected both the amplitude and the
      duration of the inhibition of ICSS produced by the neuropeptides. Our data
      indicate that endogenous peptidases are involved in the inactivation of NT and NN
      in the prefrontal cortex.

PMID- 8733749
TI  - Complete analysis of the presenilin 1 gene in early onset Alzheimer's disease.
AB  - The presenilin 1 gene has recently been identified as the locus on chromosome 14
      which is responsible for a large proportion of early onset, autosomal dominantly
      inherited Alzheimer's disease (AD). We have elucidated the intron/exon structure
      of the gene and designed intronic primers to enable direct sequencing of the
      entire coding region (10 exons) of the presenilin gene in a large number of
      families. This strategy has enabled us to find a further two novel mutations in
      the gene. We discuss the distribution of mutations and the proportions of
      autosomal dominant AD with a mean age of onset below 60 years caused by mutations
      in this gene.

PMID- 8733750
TI  - Increased startle responses in mice carrying mutations of glycine receptor
      subunit genes.
AB  - An exaggerated startle response caused by mutations of the alpha 1 subunit gene
      of the inhibitory glycine receptor (GLRA1) is the key symptom of human
      hyperekplexia or startle disease. The recessive mouse mutant spasmodic (spd)
      carries a missense mutation in the corresponding murine Glra1 gene which reduces
      the affinity of agonists for the mutant receptor. This mutant has been regarded
      as an animal model with which to investigate the molecular basis of hyperekplexia
      and related motor disorders. The recessive mouse mutant spastic (spa) carries an
      insertional mutation in the glycine receptor beta subunit gene (Glrb) that
      results in aberrant splicing and, consequently, in a reduced number of
      functionally intact receptors. The resulting phenotype is similar to that of
      spasmodic. This study measured the acoustic startle response of spasmodic and
      spastic mice under different stimulus conditions, in order to test for
      sensorimotor processing deficits in these animals. Both mutants show increased
      startle responses to acoustic stimuli of different intensities compared with wild
      type animals.

PMID- 8733751
TI  - Apamin-sensitive Ca(2+)-activated K+ channels regulate pacemaker activity in
      nigral dopamine neurons.
AB  - Mesencephalic dopamine-containing neurons exhibit a Ca(2+)-dependent oscillation
      in membrane potential believed to underlie the ability of these cells to maintain
      spontaneous activity in the absence of afferent synaptic drive. In the present
      series of experiments, sharp electrode intracellular recording techniques were
      used in conjunction with an in vitro brain slice preparation to explore the ionic
      mechanisms underlying rhythmogenesis in nigral dopamine neurons in the rat. Our
      results indicate that the K+ channel producing the prolonged post-spike
      afterhyperpolarization exhibited by these neurons is also principally responsible
      for generating the falling phase of the autogenous pacemaker oscillation.
      Alterations in the expression of this conductance are associated with marked
      changes in neuronal firing pattern, indicating that modulation of ligand-gated
      Ca(2+)-activated K+ channels may constitute a functional means of altering
      temporal coding among the major mesotelencephalic dopamine systems.

PMID- 8733752
TI  - VEP in neglect patients have longer latencies for luminance but not for chromatic
      patterns.
AB  - In patients with unilateral neglect, visual evoked potentials (VEP) to stimuli
      displayed in the left visual field are delayed compared with responses to right
      visual field stimuli. In the present study, 10 patients with right brain damage
      and neglect were tested with contrast-reversed sinusoidal gratings, modulated
      either in luminance or in chromaticity. For gratings of luminance contrast
      modulated over relatively high temporal frequencies (4-10.5 Hz), latencies of VEP
      were about 30 ms longer for stimuli presented to the contralesional (left) visual
      field than to the field ipsilateral to the lesion. For equiluminant stimuli
      modulated at relatively low temporal frequencies (1-4 Hz), however, latency was
      the same for both hemifields. As this condition activates predominately the
      parvocellular pathway the results are consistent with our previous suggestion
      that the delay observed with luminance stimuli in neglect patients results from
      selective disruption of the faster response of the magnocellular pathway.

PMID- 8733753
TI  - Successive activation of both cerebral hemispheres during cued word generation.
AB  - Most humans have a left hemispheric dominance for language. However, during
      diagnostic language testing there also is activation of the right hemisphere,
      which is probably related to attention. To investigate further the role of
      attention during language production we monitored cerebral blood flow velocities
      in the middle cerebral arteries by continuous bilateral transcranial Doppler
      ultrasonography (TCD) in nine right-handed subjects. During cued word generation,
      a successive activation of the right hemisphere in the preparatory phase, and of
      the left hemisphere during word searching was demonstrated. These findings
      indicate that attentional processes precede verbal activation and that the two
      procedures can be separated by comparative blood flow velocity measurement.

PMID- 8733754
TI  - How perceived object dimension influences prehension.
AB  - A kinematic study assessed the effects of the perceived dimensions of an object
      upon the patterning of a prehension movement involving that object. If an apple
      was perceived as two-dimensional, subjects utilized a large precision grip
      between the index finger and thumb. If the apple was perceived as three
      dimensional, whole hand prehension involving all the digits was utilized. A
      visual perturbation from perceived two-dimensional to three-dimensional at
      movement onset resulted in a transition from the 2D precision grip pattern to the
      3D whole hand prehension. These results suggest that visual mechanisms for
      interpreting the dimension of an object directly influence motor selection
      pathways, and do not necessarily access a three-dimensional central nervous
      system representation of the object.

PMID- 8733755
TI  - A role for central glucagon-like peptide-1 in temperature regulation.
AB  - We have already established that central glucagon-like peptide-1 (GLP-1) has a
      role in the central control of food intake. In this study, experiments were
      conducted to establish the effect of acute intraperitoneal (i.p.) and
      intracerebroventricular (i.c.v.) administration of GLP-1 on temperature.
      Injection of 10 micrograms GLP-1 i.c.v. caused a significant reduction in
      temperature over the subsequent 2 h and reduced food intake as expected. Both
      effects were blocked by prior i.c.v. administration of the GLP-1 antagonist
      exendin 9-39 at a ratio of 30:1. Administration of 300 micrograms GLP-1 i.p. also
      reduced temperature over the 2 h following injection but had no effect on food
      intake. Administration of exendin 9-39 alone by the i.c.v. route had no effect on
      temperature. These results indicate that GLP-1 is a neuropeptide involved in the
      regulation of temperature. Furthermore, the mechanisms that mediate the effect on
      temperature may be different from those regulating food intake given the effect
      on temperature but not food intake of i.p. GLP-1.

PMID- 8733756
TI  - Regionally distinct stoichiometry for N-methyl-D-aspartate receptor domains in
      brain.
AB  - A stoichiometric analysis of N-methyl-D-aspartate (NMDA) receptor binding was
      conducted using [3H]dizocilpine, [3H]dichlorokynurenic acid and [3H]CGP39653, and
      membranes from various brain regions of rats. The ratio of the density of
      [3H]CGP39653 binding to [3H]dizocilpine binding was > 1 in frontal cortex and
      hippocampus, approximately 1 in striatum and spinal cord and < 1 in cerebellum.
      When [3H]dichlorokynurenic acid binding was compared with [3H]dizocilpine
      binding, the ratios were > 1 in frontal cortex, hippocampus and striatum, 3-4 in
      cerebellum, and approximately 2 in spinal cord. These observations suggest that a
      single channel complex may have more than one binding site for NMDA and/or
      glycine and that the stoichiometry between the binding domains of the NMDA
      receptor varies regionally.

PMID- 8733757
TI  - Dextromethorphan potentiates morphine antinociception, but does not reverse
      tolerance in rats.
AB  - The N-methyl-D-aspartate (NMDA) and cholecystokinin (CCK)-B receptors may have a
      role in the development and reversal of tolerance to morphine. In morphine
      tolerant rats, addition of the CCK-B receptors antagonist CI 988 or the NMDA
      receptor blocker dextromethorphan enhanced the antinociceptive effect of morphine
      on the hot plate test. However, combined administration of CI 988 and
      dextromethorphan did not further potentiate the antinociceptive effect of
      morphine in tolerant rats. Dextromethorphan by itself had no effect in tolerant
      rats. In drug-naive rats, dextromethorphan by itself had no antinociceptive
      effect, but when combined with morphine or morphine and CI 988, it significantly
      potentiated the magnitude and duration of the effect of morphine. Thus, unlike
      the reversal of tolerance with CI 988 at doses that did not potentiate the effect
      of morphine, the antinociception observed with the NMDA antagonist in the
      presence of morphine in tolerant rats may not represent the reversal of
      tolerance, but may instead reflect the potentiation of morphine's analgesic
      effect by dextromethorphan.

PMID- 8733758
TI  - Anorexia induced by activators of the signal transducer gp 130.
AB  - Cytokines [interleukin (IL-1, chemokines/intercrines, interferon, tumor necrosis
      factor-alpha (TNF-alpha)] induce anorexia when administered
      intracerebroventricularly (i.c.v.) at estimated pathophysiological
      concentrations. Here, the effects of the i.c.v. microinfusion (1.0, 20 and 100
      ng) of activators of glycoprotein (gp) 130, a common signal transducer among
      receptors for members of the IL-6 subfamily [IL-6, IL-11, ciliary neurotrophic
      factor, leukemia inhibitory factor (LIF), oncostatin M (OSM)], on short-term
      feeding in rats were investigated. Several members of the IL-6 subfamily induced
      anorexia, IL-11 was the most potent, LIF the most effective, and OSM had no
      effect. The results suggest that IL-6 subfamily members act centrally to decrease
      feeding and this effect may participate in the anorexia which frequently
      accompanies pathological processes. This action could interact with the
      anorexigenic effect of other cytokines released during disease.

PMID- 8733759
TI  - Use of human tissue blocks for research.

PMID- 8733760
TI  - Isolated pulmonary Takayasu arteritis: clinicopathologic characteristics.
AB  - Involvement of the pulmonary arteries is common in systemic Takayasu arteritis
      and, in nearly all of the reported cases, the diagnosis has been based solely on
      clinical and angiographic evaluations of the patients. Isolated pulmonary
      Takayasu arteritis occurs rarely and can be diagnosed only after histologic
      examination of the appropriate tissue specimens; five such patients are described
      herein. The patients were two men and three women. Their age at diagnosis ranged
      from 25 to 66 years. The initial clinical diagnosis was thromboembolism in two
      patients, and primary pulmonary hypertension, pulmonary granulomatosis, or
      pulmonary tumor or sarcoidosis in the remaining three patients, respectively. All
      five patients underwent surgery for lung resection (three patients) or for
      reconstruction/bypass of the obstructed pulmonary arteries (two patients). Three
      types of vascular lesions were observed in the surgical specimens: the classic
      large-vessel granulomatous giant cell arteritis, a peculiar type of organized
      thrombus with prominent recanalization and neoangiogenesis, and plexogenic
      arteriopathy. Thus, the histopathologic findings of pulmonary Takayasu arteritis
      is distinctive and differs in many aspects from that of systemic Takayasu
      arteritis. Moreover, the vascular lesions of pulmonary Takayasu arteritis are
      distinguishable from those of pulmonary hypertension, sarcoidosis, and other
      types of pulmonary angiitis and granulomatosis.

PMID- 8733761
TI  - Pulmonary malakoplakia in acquired immunodeficiency syndrome: an ultrastructural
      study of morphogenesis of Michaelis-Gutmann bodies.
AB  - Malakoplakia is an unusual inflammatory reaction to a variety of infections,
      characterized by the accumulation of macrophages containing the target-like
      calcospherites, the Michaelis-Gutmann body (MGB). We report three patients with
      acquired immunodeficiency syndrome with pulmonary malakoplakia associated with
      Rhodococcus equi infection; two patients were diagnosed at autopsy and one by
      examination of a transbronchial biopsy specimen. All three patients had pulmonary
      bacterial cultures and light and electron microscopic examination. The patients
      were 33-, 41-, and 43-year old men, human immunodeficiency virus-positive for 2,
      6, 8 years, respectively. The two patients diagnosed at autopsy had cavitary
      lesions, and the patient diagnosed by biopsy specimen had nodular lesions on
      chest radiographs. Histologically, the lungs had well-circumscribed areas of
      infiltration with benign macrophages with granular cytoplasm, scattered MGBs, and
      numerous gram-positive coccobacilli. Electron microscopic examination showed
      intracellular coccobacilli, from 990 X 702 to 972 X 648 nm in diameter, with
      thick, homogenous cell walls, trilaminar cytoplasmic membranes, and dense
      cytoplasm with from one to five vacuoles. Electron microscopic studies showed
      that the bacteria within the pulmonary macrophages had thicker cell walls, less
      prominent nucleoid areas, and more vacuoles than the bacteria in cultures from
      the sputum and blood. The mature MGB ultrastructurally had a concentric,
      trilaminate structure with central mineralized core and was without recognizable
      bacterial forms. Early MGBs, however, consisted of a circular, electron-dense
      core containing bacteria, ultrastructurally similar to the R. equi seen in the
      culture. Pulmonary malakoplakia in patients with the acquired immunodeficiency
      syndrome might thus represent an acquired macrophage dysfunction of the
      intracellular digestion of phagocytized bacteria. The bacteria within the
      macrophages, however, seemed to have thicker cell walls compared with those in
      culture, and thus might be protected from enzyme digestion. It seems that MGBs
      are formed around the undigested bacteria as an alternative pathway for bacterial
      destruction, because R. equi was identified within the cores of early MGBs but
      not the mature or late stage MGBs.

PMID- 8733762
TI  - Bcl-2, p53, CD44, and CD44v6 isoform expression in neuroendocrine tumors of the
      lung.
AB  - Immunohistochemical expression of p53, bcl-2, CD44 standard (CD44S), and the v6
      isoform of CD44 (CD44v6) proteins were studied in 14 typical carcinoid tumors
      (TCs), 11 atypical carcinoids (ACs), and eight small cell carcinomas (SCLCs) in
      an attempt to use these markers of mutational events and cellular adhesion to
      discriminate neoplasms demonstrating neuroendocrine differentiation. p53 and bcl
      2 overexpression were associated with more aggressive neuroendocrine cell types.
      p53 nuclear staining was weakly positive in 21% of the TCs, whereas strong
      nuclear staining was seen in 64% of the ACs and 88% of the SCLCs (P = 0.0047).
      bcl-2 was present in 21% of the TCs, 91% of the ACs, and 100% of the SCLCs (P =
      0.0001). In contrast, CD44S and CD44v6 were inversely correlated with more
      aggressive types of neuroendocrine tumors. CD44S expression was moderate to
      strong in all of the TCs and 91% of the ACs but in only 37% of the SCLCs (P =
      0.0018). There was no correlation between expression of these markers and tumor
      size or nodal status, although loss of CD44v6 was associated with lymph node
      metastases in the TC group only. In the spectrum of neuroendocrine tumors of the
      lung, p53 and bcl-2 overexpression correlates with more aggressive histologic
      cell types. The decreasing CD44S expression in AC and SCLC is similar to findings
      in cancer of the colon and in non-small cell carcinoma of the lung, where loss of
      CD44S is associated with poor prognosis. In AC and SCLC, but not in cancer of the
      colon, loss of CD44v6 correlates with more aggressive neoplasms and might
      correlate with lymph node metastases in TCs.

PMID- 8733763
TI  - Absence of evidence for an etiologic role for Epstein-Barr virus in neoplasms of
      the lung and pleura.
AB  - Although most lung carcinomas and mesotheliomas are associated with well-known
      risk factors, these cancers develop in only a minority of persons exposed to
      known risk factors. On the other hand, these cancers develop in some patients
      without exposure to known risk factors. This indicates that other environmental
      factors play a role in the carcinogenesis of these tumors. Oncogenic viruses such
      as Epstein-Barr virus (EBC) are well-established agents in the development of
      certain cancers. EBV genomes have been detected by in situ hybridization in
      gastric adenocarcinomas and in nasopharyngeal carcinomas. To determine whether
      EBV infection is associated with pulmonary adenocarcinoma or mesothelioma, we
      performed EBV-encoded RNA-1 in situ hybridization on 80 pulmonary adenocarcinoma
      and 50 mesothelioma resection specimens. Sections were cut from paraffin-embedded
      tissue and EBV-encoded RNA-1 in situ hybridization was performed using an
      antisense oligoprobe. Sections were reviewed for the presence of EBV-encoded RNA
      1 in tumor cells. All 80 adenocarcinomas and 50 mesotheliomas were negative for
      EBV-encoded RNA-1 by in situ hybridization. In conclusion, no evidence for an
      etiologic role for EBV in the development of pulmonary adenocarcinoma or pleural
      mesothelioma was found in this study.

PMID- 8733764
TI  - Does alveolar soft-part sarcoma exhibit skeletal muscle differentiation? An
      immunocytochemical and biochemical study of myogenic regulatory protein
      expression.
AB  - There has been persistent controversy regarding the nature of cell
      differentiation in alveolar soft-part sarcoma (ASPS) since its first description
      in 1952. Some studies suggest that ASPS might represent an unusual variant of
      skeletal muscle tumor. Given the availability of new monoclonal antibodies to
      probe for skeletal muscle differentiation and the rapid advance in
      immunocytochemical techniques for deparaffinized, formalin-fixed tissue sections,
      we wished to test the proposed hypothesis that ASPS might represent a new type of
      rhabdomyosarcoma. Twelve archival samples of ASPS were retrieved, and we
      investigated the expression of two myogenic regulatory proteins, MyoD1 and
      myogenin, as well as other muscle-associated proteins, using sensitive
      immunocytochemical techniques. Despite the presence of desmin immunostaining in
      six ASPSs, no tumors were positive for either muscle actin or myoglobin. Most
      importantly, no specimen showed nuclear expression of MyoD1 or myogenin. In 11
      tumors, however, there was considerable granular immunostaining in the tumor cell
      cytoplasm with the anti-MyoD1 monoclonal antibody 5.8A, a phenomenon observed in
      various nonmuscle normal and neoplastic tissues with this antibody. To analyze
      the exact nature of immunostaining of MyoD1 and desmin in ASPS, biochemical
      analyses using available fresh frozen tumor tissue were performed. Although a 53
      kDa band was noted with antidesmin antibody on Western blot analysis, no specific
      protein band that corresponds to the 45-kDa MyoD1 was detected with antibody
      5.8A. These results confirm the presence of desmin in ASPS but argue against
      authentic expression of MyoD1. They also suggest that the cytoplasmic
      immunostaining observed with anti-MyoD1 antibody 5.8A most likely represents a
      nonspecific cross-reaction with an unknown cytoplasmic antigen. Considering the
      master role that MyoD1 and myogenin play in skeletal muscle commitment and
      differentiation and the lack of expression of these two proteins in ASPS as
      determined immunocytochemically and biochemically, we think that the histogenesis
      of ASPS remains unknown.

PMID- 8733765
TI  - CD44v6 expression in primary bronchioloalveolar carcinoma and conventional
      pulmonary adenocarcinoma.
AB  - CD44 is a family of transmembrane glycoproteins involved in cell-to-cell and cell
      to-matrix interactions. Of the CD44 isoforms characterized, the v6 variant has
      been shown to confer metastatic potential in animal models and its expression has
      been correlated with aggressive behavior in some human malignancies. In an
      attempt to provide further insight into the heterogeneous appearance and behavior
      of bronchioloalveolar carcinomas (BACs), the pattern of CD44v6 staining in five
      mucinous, five nonmucinous, and eight sclerosing stage I BACs were compared with
      12 comparably staged conventional pulmonary adenocarcinomas (CPAs). Formalin
      fixed, paraffin-embedded sections were stained with monoclonal antibodies to
      CD44v6 (clone VFF-7). Neoplastic goblet cells, whether growing in a lepidic
      pattern in mucinous BACs or in an invasive pattern in CPAs, consistently
      demonstrated low level expression of CD44v6. In contrast, lepidic growth by
      neoplastic cells of type 2 pneumocyte or Clara cell differentiation demonstrated
      high levels in five of five cases of nonmucinous BACs, seven of eight cases of
      sclerosing BACs, and six of nine cases of CPAs. Similar cells of type 2
      pneumocyte or Clara cell differentiation within the scarred area of sclerosing
      BAC demonstrated an intermediate degree of staining with four of eight cases
      marking with high levels, whereas none of the nine cases of CPAs with invasion by
      these cells showed high levels in the desmoplastic areas. From these results, two
      patterns of CD44v6 expression were recognized in BACs and CPAs. First, the
      expression appeared to be partly dependent on differentiation as cells
      demonstrating mucinous differentiation, whether in BACs or CPAs, consistently
      lacked CD44v6 staining. Second, in cells of type pneumocyte or Clara cell
      differentiation the expression was dependent on the growth pattern and their
      relationship to the stroma. High level expression was noted in neoplastic cells
      growing in a lepidic pattern, whereas those demonstrating invasion gradually lost
      the expression with increasing degrees of stromal reaction. Thus, the expression
      of CD44v6 in pulmonary BACs and similarly staged CPAs appears to be different
      from other human malignancies that have a positive correlation with aggressive
      behavior.

PMID- 8733766
TI  - Clear cell adenocarcinoma of the urethra: a clinicopathologic analysis of 19
      cases.
AB  - Nineteen clear cell adenocarcinomas of the urethra, 18 from women and one from a
      man, are described. The patients ranged from 35 to 80 years of age (average, 58
      yrs). The clinical presentation and gross findings were similar to those of
      urethral carcinomas, except that 12 tumors, all from women, arose within a
      urethral diverticulum. On microscopic examination, the neoplasms exhibited the
      classic triad of tubulocystic, papillary, and diffuse patterns that characterize
      this tumor. The tumors had the typical cytologic features of clear cell
      adenocarcinoma, including hobnail cells, flattened cells, and cells with abundant
      clear cytoplasm. Nuclear pleomorphism was typically at least moderate and was
      marked in almost half the specimens. Mitotic figures were easily found in almost
      all the specimens. These cytologic features should aid in distinction of this
      carcinoma from the benign nephrogenic adenoma, although one of our patients was
      initially misdiagnosed as having the latter. Immunostaining for prostate-specific
      antigen and prostatic acid phosphatase was performed on 13 tumors, and all were
      negative. Follow-up is available for 13 patients. Six of them had no evidence of
      recurrence up to 10 years postoperatively. Four patients died of disease from 5
      months to 42 months postoperatively. Three additional patients have had
      recurrence but were alive up to 6.5 years after presentation. We conclude that
      urethral clear cell adenocarcinoma occurs in adults, and in women in the great
      majority of cases; has a particular association with a urethral diverticulum,
      which has been present in 56% of the patients; is indistinguishable from clear
      cell adenocarcinoma of the female genital tract but is not associated with
      endometriosis; probably does not arise by malignant transformation of nephrogenic
      adenoma; is usually readily distinguished from the latter because of greater
      cytologic atypicality and mitotic activity; and does not stain for prostate
      specific antigen or prostatic acid phosphatase.

PMID- 8733767
TI  - Coexistence of primary empty sella and silent corticotrophic adenoma.
AB  - Primary empty sellae are rarely associated with an intact pituitary adenoma. Most
      of such cases are documented clinically and radiographically. This paper reports
      a case of coexistence of primary empty sella and a silent corticotrophic adenoma
      in a 61-year-old woman. The en bloc preparation of the sella turcica demonstrates
      the anatomical relationship of the empty sella and the flattened pituitary gland
      and the adenoma. The immunostain shows the presence of all five cell types of the
      adenohypophysis.

PMID- 8733768
TI  - Expression of Pit-1 and estrogen receptor messenger RNA in prolactin-producing
      pituitary adenomas.
AB  - The pituitary-specific transcriptional factor, Pit-1, is a member of the POU
      domain family, which has a role in the development and differentiation of three
      pituitary cell types: somatotrophs, lactotrophs, and thyrotrophs. Recently,
      specific DNA-dependent interactions have been observed between Pit-1 and nuclear
      receptors, including: thyroid hormone receptor; retinoic acid receptor;
      glucocorticoid receptor; and estrogen receptor (ER). The cooperative interaction
      between Pit-1 and ER required for prolactin enhancer activity in rat pituitaries
      has been suggested. We analyzed the expression of Pit-1 messenger ribonucleic
      acid (mRNA) and ER mRNA in 15 human prolactin-producing adenomas using
      nonradioisotopic in situ hybridization. Their products were also studied by
      immunohistochemical analysis. Pit-1 mRNA was detected in 12 (80%) of 15 prolactin
      producing adenomas. On the other hand, ER mRNA was detected in 14 (94%) of
      adenomas studied. mRNAs of Pit-1 and ER were detected more frequently than
      immunohistochemical expression of their products. By combined in situ
      hybridization and immunohistochemical examination, Pit-1 mRNA and ER mRNA were
      often colocalized with prolactin immunoreactivities. The colocalizations of Pit-1
      mRNA and ER protein were observed in adenoma cells. The high incidence of the
      expression of ER mRNA in prolactin-producing adenomas may suggest cooperative
      interactions between Pit-1 and ER in functional differentiation and development
      of prolactin-producing adenomas.

PMID- 8733769
TI  - Malignant lymphoma of the adrenal gland: its possible correlation with the
      Epstein-Barr virus.
AB  - Initial manifestation of malignant lymphoma in the adrenal gland is a rare event,
      and clinical and pathologic features are not fully understood. We conducted a
      nationwide study in Japan, and 20 patients with malignant lymphoma that showed
      initial and main manifestation in the adrenal gland were identified. Clinical and
      pathologic findings were summarized. In addition, the presence of the Epstein
      Barr virus (EBV) genome in the tumor cells was examined by using polymerase chain
      reaction (PCR) and in situ hybridization (ISH), together with the
      immunohistochemical evaluation of the expression of latent membrane protein-1
      (LMP-1). There were 13 men and seven women; their ages at admission ranged from
      40 to 87 years (median, 65 yr). Fever, anemia, and elevation of lactic
      dehydrogenase levels were the common presenting findings. One patient had
      acquired immunodeficiency syndrome. Adrenal tumors were bilateral in 15 patients
      and unilateral (all in the left site) in five. Prognosis was very poor; all but
      two patients died within 1 year after admission. Histologically diffuse large
      cell type was the commonest type (14 specimens). Immunohistologically, 16
      specimens were B-cell type, and one was T-cell type. Another three specimens
      showing no positive reaction for any antibodies were also judged as B-cell type
      on purely morphologic grounds. Prominent intravascular proliferation of tumor
      cells was found in five patients. PCR for EBV genomes gave positive results in
      five patients; the virus was subtyped as A in three patients and as B in two. The
      ISH provided positive signals in nine samples, including all five specimens
      positive for PCR. Four of the nine cases with detectable EBV by PCR and/or ISH
      expressed LMP-1. The present study shows that adrenal lymphoma is EBV associated
      and has a B-cell phenotype.

PMID- 8733770
TI  - Immunohistochemical and molecular evaluation of the mdm-2 gene product in
      bronchogenic carcinoma.
AB  - In this study, we investigated immunohistochemically the expression of mdm-2
      protein in 93 surgically resected bronchogenic carcinomas. The findings were
      correlated with p53 protein detection status and clinicopathologic data
      (histologic type, differentiation grade of the lesions, lymph node metastases,
      and smoking history of the patients). Thirty of the 93 immunohistochemically
      examined specimens were subjected to Northern blot and differential polymerase
      chain reaction analysis to look into the mechanism of mdm-2 overexpression.
      Finally, we studied the concordance between p53 immunohistochemical positivity
      and p53 gene alterations as assessed by the single-strand conformation
      polymorphism technique. Seventy-three (78%) and 67 (72%) of 93 carcinomas showed
      nuclear immunoreactivity for mdm-2 and p53 proteins, respectively. We observed a
      high degree of concordance (75%) between p53 mutations and p53 immunolabelling,
      which was even higher in the specimens with p53 positively in more than 50% of
      the cells (90%). Despite the high percentage of mdm-2 and p53 expression, the two
      molecules were simultaneously detected in 50 (54%) of 93 cases. Forty-two (84%)
      of the 50 cases were accompanied by p53 mobility shifts, which indicated
      mutations. Interestingly, statistical analysis revealed an almost significant
      correlation between the carcinomas with mdm-2/p53 coexpression and lymph node
      disease (P = 0.058), which indicated a possible "gain of function" phenotype. In
      addition, absence of reactivity for both proteins was statistically more frequent
      in the patients without lymph node disease (P = 0.006). The mdm-2-positive/p53
      negative immunohistochemical profile was more often seen in adenocarcinomas (P =
      0.003), especially in well-differentiated ones (P = 0.02), than in other
      histologic types of lung cancer, which suggested a p53-independent pathway of mdm
      2 overexpression. Molecular analysis showed that mdm-2 overexpression was a
      consequence of increased transcription rather than of mdm-2 gene amplification.
      The smoking history of the patients was strongly related to p53 (P = 10(-4)) even
      in the group of adenocarcinomas (P = 0.012). No correlation was observed between
      cigarette consumption and mdm-2 immunoreactivity.

PMID- 8733771
TI  - Immunohistochemical detection of bcl-2 protein in adenocarcinoma and non
      neoplastic cellular compartments of the lung.
AB  - The expression of bcl-2 seems to influence the biologic activity of a variety of
      neoplasms. In this study, we examined bcl-2 protein expression in 47 surgically
      resected adenocarcinomas of the lung to determine its expression in the
      neoplastic and adjacent non-neoplastic cells. Seven squamous cell carcinomas, six
      small cell carcinomas, five non-neoplastic lung lesions, and five normal lungs
      were also studied. The bcl-2 protein was detected after antigen retrieval with
      bcl-2 monoclonal antibody using archival formalin-fixed, paraffin-embedded tissue
      material. Fifty-one of 52 cases had bronchioles that could be evaluated and all
      expressed bcl-2, and of these, 12 showed basal immunostaining, 17 showed luminal
      immunostaining, and 22 showed immunostaining in both cellular compartments.
      Thirty of the 47 adenocarcinomas expressed bcl-2, whereas four of seven squamous
      cell carcinomas and all six small cell carcinomas were bcl-2 positive. bcl-2
      immunostaining was correlated with a survival using the Fisher exact test. There
      were no statistically significant differences in survival between patients with
      bcl-2-positive and bcl-2-negative adenocarcinomas (P = 0.332). Similar results
      were obtained using the Kaplan-Mier product limit survival analysis method (P =
      0.356). Our study also showed that expression of bcl-2 is common in pulmonary
      adenocarcinomas and that bcl-2 expression may be found in the basal and the
      luminal surfaces of normal bronchioles.

PMID- 8733772
TI  - Bilateral mucosa-associated lymphoid tissue lymphomas of parotid glands: a 13
      year interval.
AB  - Benign lymphoepithelial lesions of salivary gland may have a population of
      monoclonal B cells. There is controversy regarding the clinical significance of
      monoclonality in these lesions. Morphologically and clinically, benign
      lymphoepithelial lesions of the salivary gland with monoclonal B cells falls
      within the spectrum of low-grade B-cell lymphomas of mucosa-associated lymphoid
      tissue. We report a case of bilateral parotid lymphomas of mucosa-associated
      lymphoid tissue, separated diagnostically by a 13-year interval. Polymerase chain
      reaction analysis detected similar clones in the bilateral parotid glands. This
      finding supports the natural history of mucosa-associated lymphoid tissue
      lymphomas. In addition, because mucosa-associated lymphoid tissue lymphomas have
      an unpredictable period of localized disease, recognition of monoclonality in
      benign lymphoepithelial lesions of salivary glands is important for local cure
      and can be aided by combining histologic with immunohistochemical, flow
      cytometric immunophenotyping, and Southern blot and/or polymerase chain reaction
      analysis.

PMID- 8733773
TI  - Morphogenesis of inclusion bodies of urothelial carcinoma: a case study.
AB  - The morphogenesis of inclusions of urothelial carcinoma (K. Donhuijsen et al.:
      Hum Pathol 23:860, 1992) is described in a case of a 51-year-old man with poorly
      differentiated urothelial carcinoma. Peritoneal fluid preparations contained
      numerous dyscohesive, large, anaplastic cells with abundant dense amphophilic
      cytoplasm often compartmentalized into multiple, variably sized, intracytoplasmic
      lumina, each containing "bull's eye"-like inclusions, with a periodic acid Schiff
      positive refractile central core and an alcian blue/mucicarmine-positive rim.
      Ultrastructurally, the progression of osmiophilic substance from membrane-bound
      exocrine-type secretory granules, via exocytosis, to a presence in both
      intracytoplasmic lumina and extracellular space has been documented.
      Immunohistochemically, the periodic acid Schiff-positive refractile cores, as
      well as the minute periodic acid Schiff-positive granules in the cytoplasm,
      stained positively for secretory component and peanut agglutinins, whereas the
      alcian blue-positive mucinous material, which coated the refractile cores as well
      as the lining of the intracytoplasmic lumina, stained strongly for epithelial
      membrane antigen and leu M1. Ultrastructurally, protein A-gold probes,
      immunolabeled for peanut agglutinin and secretory component, were localized to
      the osmiophilic substance.

PMID- 8733774
TI  - DNA image analysis of urinary cytology: prediction of recurrent transitional cell
      carcinoma.
AB  - To evaluate the utility of image analysis in monitoring patients with
      transitional cell carcinoma, we studied, by cytologic means and by image
      analysis, 78 urinary tract specimens from 66 patients, of whom 49 (74%) had a
      previous history of transitional cell carcinoma. The specimens consisted of 51
      (65%) voided urine specimens, 12 (15%) bladder washings, 8 (10%) ureteral
      washings, 3 (4%) ureteral brushings, 2 (3%) renal pelvic washings, and 2 (3%)
      catheterized urine specimens. DNA histograms were classified into five patterns
      on the basis of their DNA index and the percentage of their cells with DNA
      content greater than 5c: diploid (single peak in the 2c region with no cells
      greater than 5c), intermediate (diploid with less than 10% of cells greater than
      5c), aneuploid (single peak or multiple peaks between the 2c and 4c region or
      more than 10% of cells greater than 5c), tetraploid (at least 10% of cells in the
      4c region and a corresponding peak at 8c), and polyploid (multiple peaks in the
      2c, 4c, 8c, and 10c regions). Of the 78 cases, 22 were diploid, 24 were
      intermediate, 29 were aneuploid, one was tetraploid, and two were polyploid.
      Histologic confirmation or clinical follow-up was found in 29 aneuploid cases, 13
      intermediate cases, and one diploid case. Most cases of carcinoma in situ (five
      of six) and invasive tumors (12 of 17) were aneuploid. The sensitivity was 100%,
      and the specificity was 73% when cytologic and image analysis results were
      combined. We conclude that image analysis, when combined with cytologic
      examination, is a reliable noninvasive diagnostic test for monitoring patients
      with transitional cell carcinoma; aneuploidy is specific for malignancy; and the
      presence of cells greater than 5c, although frequently associated with tumor
      recurrence, can be seen in non-neoplastic conditions.

PMID- 8733775
TI  - Pathology of selected neoplasms of the central nervous system.

PMID- 8733776
TI  - Medullary carcinoma of the thyroid: subtypes and current management.

PMID- 8733777
TI  - Management of sinusitis.

PMID- 8733778
TI  - Sudden sensorineural hearing loss: an otologic emergency.

PMID- 8733779
TI  - Phonosurgery.
AB  - Phonosurgery is composed of procedures that are intended to maintain or improve
      the quality of the voice by correcting defects in laryngeal sound production.
      These procedures are rooted in a rich medical history that dates back to the
      early 19th century. There has been a recent convergence of physiologic principles
      of voice production with surgical technique theory. Recognition of this
      interdependence has provided a catalyst for collaboration among surgeons,
      scientists, speech pathologists, vocal pedagogists, and performing artists. We
      live in a society that is linked to effective communication, and there is a
      growing population of individuals who have professional voice responsibilities as
      part of everyday life. This has created a need for the recent developments in
      phonosurgery and its emergence as a subspecialty of otolaryngology.

PMID- 8733780
TI  - Medical problems of professional voice users.

PMID- 8733781
TI  - Thyroid nodules and nodular thyroids: a clinical overview.

PMID- 8733782
TI  - The diagnosis and management of hoarseness.

PMID- 8733783
TI  - Management of parotid swelling.

PMID- 8733784
TI  - Preoperative assessment and perioperative management of cardiac ischemic risk in
      noncardiac surgery.

PMID- 8733785
TI  - Intraoperative electrophysiological and objective tests after cochlear re
      implantation in a young child.
AB  - The electrically evoked auditory brainstem response (EABR) and stapedius reflex
      threshold (ESRT) are routinely recorded during implant surgery with the Nucleus
      22 channel cochlear implant in the Nottingham Paediatric Cochlear Implant
      Programme and are extremely valuable in the management of young implanted
      children. These intraoperative tests were carried out in a young child on the
      occasion of the first implantation and then after re-implantation 17 months later
      following malfunction of the first device. The surgical experiences of the first
      implantation and the re-implantation were both straightforward. Recordings of the
      intraoperative EABR and ESRT were typical of the expected pattern of responses on
      both occasions and there was only a small reduction in threshold sensitivity
      after re-implantation. These investigations provide valuable objective
      information to support and assist with the management of re-implantation in a
      young child.

PMID- 8733786
TI  - Real ear to coupler differences in children having otitis media with effusion.
AB  - The aim of this study was to investigate the effects of otitis media with
      effusion (OME) on the 'real ear to coupler difference' (RECD) in children. RECDs
      are important in the procedures used for selection of appropriate amplification
      characteristics for children with permanent (usually sensorineural) hearing
      impairment. Subjects were 28 children aged between 4.6 and 7.6 years, 14 of whom
      had OME. There was no evidence of middle ear pathology in the remaining 14 who
      comprised the control group. All real-ear and coupler measures showed good test
      retest repeatability at 4.0 kHz and below. The mean RECDs in frequency range 0.2
      3.0 kHz were found to be up to 3.5 dB greater for the children having OME than
      for those without OME, although when statistically analysed only the differences
      in RECD at 1.0 kHz and 1.5 kHz were significant. Due to low correlation between
      the root mean square (RMS) sound pressure level (SPL) in the ear canal and ear
      canal volume, and low correlation between the subject's maximum RECD and ear
      canal volume, neither of these other variables could be used to predict an
      individual's RECD in this study. Large inter-subject variability was found, with
      a maximum standard deviation of 5.6 dB at 0.2 kHz, so this study greatly supports
      the need for individual RECD measurements to be made whenever possible, rather
      than using averaged transformation figures, particularly if the individual has
      OME.

PMID- 8733787
TI  - Transient evoked otoacoustic emissions in occupational medicine as an auditory
      screening test for employment.
AB  - TEOAEs are considered a valuable test for specific evaluation of the inner ear
      function and can be used as a screening method for an objective diagnosis of
      cochlear damage. The aim of this study was the evaluation of TEOAEs as a
      diagnostic tool for adult male subjects undergoing medical selection for
      recruitment in the Italian Air Force (IAF). The analysis was performed with ILO88
      System on 30 normal and 83 hearing-impaired subjects. Only cochlear hearing
      losses were considered and categorized in three classes: unilateral (UHL),
      bilateral (BHL), high frequencies (HFHL: cochlear damage only at 6 and/or 8 kHz).
      TEOAE intensity, reproducibility and spectrum were the main parameters
      investigated. A qualitative comparison between the responses obtained in the two
      ears of the same subject was also performed. Moreover, TEOAE spectra and Pure
      Tone Audiometry (PTA) data were compared. Significant differences between the
      normal and the affected ear in UHLs were found, while no variations between the
      two ears were observed in BHLs and HFHLs. A high correlation between TEOAE
      spectrum and PTA was reported in normals and UHLs. The global test sensitivity
      was high in UHLs (94%) and BHLs (83%), while specificity was 85.0% in the normal
      sample. Although significant limitations reduce their efficiency, TEOAEs can be
      regarded as a useful complementary test to standard PTA for audiological
      selective purposes.

PMID- 8733788
TI  - Skin lesions arising from electrode placement.

PMID- 8733789
TI  - Cytochromes and psychotropic drug interactions.

PMID- 8733790
TI  - 'Audible thoughts' and 'speech defect' in schizophrenia. A note on reading and
      translating Bleuler Traduttori traditori.

PMID- 8733791
TI  - Consent to neuroleptic medication for schizophrenia: clinical, ethical and legal
      issues.
AB  - BACKGROUND: The effects of neuroleptic medication on schizophrenic patients are
      both positive (reduction in symptoms) and negative (adverse side-effects). Given
      that altered cognitive functioning may be a feature of schizophrenia, the use of
      neuroleptics raises important ethical and legal issues. METHOD: A selective
      review was carried out of papers addressing ethical arguments for and against
      obtaining consent from schizophrenic patients, and the ethical and legal
      requirements which must be met for consent to occur. RESULTS: Although a balance
      must be met between arguments for and against obtaining consent, clinicians
      should seek informed consent in all but exceptional circumstances. Obtaining
      consent depends on the adequate presentation of information, the absence of
      duress and the patients' capacity to consent. Various tests of capacity to
      consent have been proposed. CONCLUSIONS: It is proposed that clinicians employ a
      proforma to record attempts to obtain informed consent during routine clinical
      practice.

PMID- 8733792
TI  - Verbal creativity, depression and alcoholism. An investigation of one hundred
      American and British writers.
AB  - BACKGROUND: An earlier study of 291 world famous men had shown that only visual
      artists and creative writers were characterised, in comparison with the general
      population, by a much higher prevalence of pathological personality traits and
      alcoholism. Depressive disorders, but not any other psychiatric conditions, had
      afflicted writers almost twice as often as men with other high creative
      achievements. The present investigation was undertaken to confirm these findings
      in a larger and more comprehensive series of writers, and to discover causal
      factors for confirmed high prevalences of affective conditions and alcoholism in
      writers. METHOD: Data were collected from post-mortem biographies and, where
      applicable, translated into DSM diagnoses. The frequencies of various
      abnormalities and deviations were compared between poets, prose fiction writers,
      and playwrights. RESULTS: A high prevalence in writers of affective conditions
      and of alcoholism was confirmed. That of bipolar affective psychoses exceeded
      population norms in poets, who in spite of this had a lower prevalence of all
      kinds of affective disorders, of alcoholism, of personality deviations, and
      related to this, of psychosexual and marital problems, than prose fiction and
      play writers. CONCLUSIONS: A hypothesis is developed, which links the greater
      frequency of affective illnesses and alcoholism in playwrights and prose writers,
      in comparison with poets, to differences in the nature and intensity of their
      emotional imagination. This hypothesis could be tested by clinical psychologists
      collaborating with experts in literature on random samples of different kinds of
      writers.

PMID- 8733793
TI  - Obstetric complications and schizophrenia: a case control study based on
      standardised obstetric records.
AB  - BACKGROUND: There have been many reports of a higher incidence of 'obstetric
      complications' in the histories of schizophrenics than of controls, but because
      of the methodological shortcomings of most of these comparisons the relationship
      remains controversial. METHOD: Comprehensive records covering all psychiatric
      hospital admissions and all hospital deliveries in Scotland since 1971 made it
      possible to identify the obstetric records of people born in 1971-74 who were
      subsequently admitted to hospital with a diagnosis of schizophrenia, and then to
      compare their standardised obstetric records with those of closely matched
      controls. RESULTS: One hundred and fifteen schizophrenic/control pairs were
      compared. The former showed a highly significant (P < 0.001) excess of
      complications of both pregnancy and delivery. In particular, there was a
      significant excess of pre-eclampsia (10 v. 2) and of infants detained in hospital
      for neonatal care (18 v. 6). CONCLUSION: The raised incidence of obstetric
      complications often reported in people with schizophrenia is genuine and probably
      contributes to the aetiology of the condition.

PMID- 8733794
TI  - Four behavioural syndromes of schizophrenia.
AB  - BACKGROUND: A complementary approach to defining symptomatic subtypes of
      schizophrenia is to identify characteristic patterns of 'problem behaviours'
      associated with the capacity of patients to function in the community. METHOD: In
      a large epidemiological survey, patients fulfilling Feighner criteria for
      schizophrenia were identified by key informants and assessed using the MRC Social
      Behaviour Schedule (SBS) and the Manchester Scale. An exploratory factor analysis
      was used to extract behavioural syndromes from the SBS data in order to compare
      the syndrome profiles in community, acute and long-stay subgroups and to examine
      their associations with symptoms and social functioning. RESULTS: Four
      behavioural syndromes were identified: 'Thought disturbance', 'Social
      withdrawal', 'Depressed behaviour' and 'Anti-social behaviour', which
      distinguished between the patient subgroups and had significant differential
      relationships to symptoms and social functioning variables. CONCLUSIONS: The
      evaluation of disability in schizophrenia and effectiveness of treatment
      interventions is incomplete without an assessment of problem behaviours.

PMID- 8733795
TI  - Idazoxan and response to typical neuroleptics in treatment-resistant
      schizophrenia. Comparison with the atypical neuroleptic, clozapine.
AB  - BACKGROUND: We investigated whether antagonism of alpha 2 adrenergic receptors
      would augment treatment response in schizophrenia, by administering idazoxan, an
      alpha 2 antagonist drug, to treatment-resistant patients on typical neuroleptics.
      METHOD: Seventeen hospitalised treatment-resistant patients with DSM-III-R
      schizophrenia or schizoaffective disorder were studied on typical neuroleptic
      treatment, on treatment with idazoxan plus typical neuroleptic, and after
      discontinuation of idazoxan, in fixed, non-random order, and under double-blind,
      placebo-controlled conditions. RESULTS: The addition of idazoxan to fluphenazine
      treatment resulted in significant reductions of global psychosis and total,
      positive and negative symptoms on the Brief Psychiatric Rating Scale, compared to
      neuroleptic treatment alone. Symptom improvement significantly correlated with
      idazoxan-induced changes in indices of noradrenergic function. In a subgroup of
      patients, idazoxan plus typical neuroleptic treatment compared favourably with
      clozapine treatment, when both were compared to typical neuroleptic treatment
      alone. CONCLUSIONS: The antagonism of alpha 2 receptors augmented therapeutic
      response to typical neuroleptic treatment in treatment-resistant patients with
      schizophrenia. This antagonism may contribute to clozapine's superior
      antipsychotic effects.

PMID- 8733796
TI  - Links between expressed emotion and burden of care in relatives of patients with
      schizophrenia.
AB  - BACKGROUND: Findings that the EE level of a relative may change over time support
      the idea that EE may represent the circumstances of the relationship between
      patient and caregiver. The present study examines to what extent EE levels in
      relatives are related to relatives' burden of care and their perceptions of
      patients' deficits in social role performance. METHOD: Fifty patients recently
      admitted to hospital with DSM-III-R diagnoses of schizophrenia or
      schizophreniform disorder were assessed for positive and negative symptoms. Fifty
      relatives who were living or were in close contact with these patients were
      interviewed for the assessment of EE and burden or care, and to provide
      information about patients' social role performance and social and behaviour
      problems. RESULTS: High-EE relatives had considerably higher mean scores for
      burden of care then low-EE relatives relatives (12.5 v. 6.8, respectively, P =
      0.002), and perceived more deficits in patients' social functioning than low-EE
      relatives (means: 16.2 v. 6.9, respectively, P = 0.004). The employment status of
      relatives was the only socio-demographic characteristic of relatives and patients
      associated with EE levels, those who were working being less likely to be high
      EE. Patients' psychopathology was not associated with EE levels and burden of
      care. CONCLUSIONS: This study shows that EE and the burden of care are related.
      EE and burden both measure aspects of the relationship between relatives and
      patients. These findings suggest that EE and burden of care are more dependent on
      relatives' appraisal of the patient condition than on patients' actual deficits.

PMID- 8733797
TI  - The effectiveness of cognitive therapy in the treatment of non-psychotic morbid
      jealousy.
AB  - BACKGROUND: Although a cognitive-behavioural formulation of morbid jealousy has
      been described there is little empirical research into the practical usefulness
      of this model. This study evaluated the effectiveness of treating non-psychotic
      morbid jealousy using a cognitive approach. METHOD: Cognitive-behavioural and
      emotional measures of jealousy were calibrated by comparison with 40 non-jealous
      normal controls. These instruments were used as measures of change to assess the
      effectiveness of cognitive therapy in altering cognitive errors in 30 morbidly
      jealous out-patient referrals, divided into delayed and immediate treatment
      subgroups to assess the stability of the condition. Both groups completed all
      measures immediately before and after treatment, and at follow-up. RESULTS: The
      instruments demonstrated significant differences between jealous and non-jealous
      subjects on cognitive-behavioural and emotional aspects of jealousy. The delayed
      treatment group showed no significant alteration in scores on any of the
      instruments after 12 weeks on the waiting list, confirming the stability of the
      condition. In the majority of cases cognitive therapy aimed at the modification
      of dysfunctional cognitive processes resulted in a significant improvement on all
      jealousy measures, immediately after treatment and at follow-up. The improvement
      reported by patients was supported by the partner's ratings. CONCLUSION: The
      results support the postulation of the cognitive model that modification of
      cognitive schema by a schema-focused treatment package results in a significant
      reduction in disturbance in all aspects of the jealousy syndrome.

PMID- 8733798
TI  - Present use of the Hamilton Depression Rating Scale: observation on method of
      assessment in research of depressive disorders.
AB  - BACKGROUND: The Hamilton Depression Rating Scale retains its primacy in research.
      There have been recent important critiques. It is clear that instructions
      provided by its author are widely overlooked. METHOD: A survey of the present use
      of the HDRS was conducted by inspection of five major journals publishing studies
      in the field of psychiatry. Note was especially made of whether a recognised
      version of the Scale was quoted; also of whether authors had selected specific
      scores on one or other of the versions to indicate a criterion for inclusion of a
      subject in a study, and likewise whether a specific score had been selected as an
      indication of recovery following some procedure or treatment. RESULTS: One
      hundred and fourteen articles were reviewed in which 71 had used a depression
      scale. This was the HDRS in 66% of the studies. There was considerable evidence
      that the instruction that the HDRS was only to be used in situations where the
      patient had received a diagnosis of a primary depressive illness had been
      ignored. There was considerable degree of arbitrary selection of Scale scores.
      CONCLUSION: The survey causes concern about the methodology of much research in
      the field as of assessment of severity of psychiatric disorder. The rationale of
      assessment by the rating scale method is considered and suggestion made for
      improvement in research practice.

PMID- 8733799
TI  - One and two year outcomes for adults with learning disabilities discharged to the
      community.
AB  - BACKGROUND: Long-stay patients with learning disabilities (n = 214) were assessed
      in hospital and 12 and 24 months after discharge in order to examine the effects
      of relocation. METHOD: Each resident acted as his/her own control in a
      prospective repeated-measures design. Skills and behavioural problems were
      assessed by keyworkers. Self-perceived quality of life was obtained during
      interviews with researchers who also completed an environmental checklist of the
      residents' accommodation. RESULTS: There was little or no change in people's low
      pre-discharge skill levels. Certain aspects of problem behaviour improved after
      12 months, although socially unacceptable behaviour increased slightly. People
      were less depressed (P < or = 0.01) 12 months after discharge (N = 119) and were
      more satisfied (P < or = 0.05) with their new 'homes' (n = 108). There were few
      changes in the pattern of activities or the social networks of people 12 months
      later. Little or no further change in outcomes was reported 24 months after
      discharge. CONCLUSIONS: The implementation of the deinstitutionalisation policy
      in Northern Ireland has been limited by the predominance of residential and
      nursing homes and the lack of 'ordinary' accommodation. There is a need for
      purchasers and providers to give more attention to ways in which the principles
      of normalisation could be incorporated in the process of contracting and
      delivering services.

PMID- 8733800
TI  - Demographic and obstetric risk factors for postnatal psychiatric morbidity.
AB  - BACKGROUND: Postnatal depression follows 10% of live births but there is little
      consensus on the risk factors associated with its development. Previous smaller
      studies have been unable to quantify the impact of independent risk factors as
      relative and attributable risks. METHOD: The Edinburgh Postnatal Depression Scale
      (EPDS) was used to screen a systematic sample of 2375 women, six to eight weeks
      after delivery. Information on socio-demographic and obstetric variables was
      collected at the screening interview. The risk factors associated with high EPDS
      scores (> 12) were determined and entered stepwise into a regression model.
      RESULTS: Four independent variables were found to be associated with an EPDS
      score above this threshold. These were an unplanned pregnancy (OR 1.44); not
      breast-feeding (OR 1.52), and unemployment in either the mother, i.e. no job to
      return to following maternity leave (OR 1.56), or the head of household (OR
      1.50). These four variables appeared to explain the risk associated with other
      risk factors. CONCLUSIONS: Although a direct aetiological role for these risk
      factors is not certain, they may indicate strategies for the prevention of
      affective morbidity in postnatal women. These may include reducing unwanted
      pregnancy and employment for women after childbirth.

PMID- 8733801
TI  - Drug and alcohol problems among individuals with severe mental illness in south
      London.
AB  - BACKGROUND: High rates of comorbid alcohol and drug disorders have previously
      been found among individuals with severe mental illnesses such as schizophrenia
      and bipolar affective disorders. Clinical and social outcomes have been reported
      to be worse in this group and service costs greater than in individuals with
      severe mental illness only. These 'dual diagnosis' patients have mainly been
      investigated in the USA, and there has been very little research in Europe, where
      patterns of substance abuse may be different. METHOD: All patients with psychotic
      illnesses who had any contact with the mental health services in a geographically
      defined sector in South London over a specified period were studied. Individuals
      with problems related to alcohol or drugs were identified using standardised
      interviews with subjects and their keyworkers. Data on psychiatric service use
      during the previous 2 years were also obtained. RESULTS: One hundred and seventy
      one subjects with psychotic illnesses were interviewed (response rate: 78.4%).
      The one-year prevalence rate for any substance problem was 36.3% (95% CI = 29.1
      43.5), for alcohol problems it was 31.6% (95% CI = 24.6-38.5), and for drug
      problems 15.8% (95% CI = 10.3-21.3). Young male subjects were at higher risk of
      having substance problems. Patients with substance problems had spent almost
      twice as many days in hospital as those without such problems over the previous
      two years (difference = 26.3 days, 95% CI = 3.8-48.7). CONCLUSIONS: The
      prevalence of substance problems among people suffering from severe mental
      disorders is high, and seems to be associated with greater use of in-patient
      services. This is a significant clinical problem, with cost implications. Further
      investigation is needed for adequate service provision.

PMID- 8733802
TI  - Does familiality predispose to both emergence and persistence of psychosis? A
      follow-up study.
AB  - BACKGROUND: It as been suggested that in schizophrenia an association exists
      between family history of schizophrenia and poor outcome on the one hand, and
      family history of affective disorders and good outcome on the other. METHOD: We
      tested for associations between four-year outcome and familial loading for
      psychotic disorders in a mixed sample of 150 consecutively admitted patients with
      functional psychosis (schizophrenia, psychotic affective disorders, other
      psychotic disorders) of recent onset. For each proband, a familial loading score
      for (i) broadly defined psychotic disorder, (ii) schizophrenia, and (iii)
      affective disorder was calculated using information on relatives obtained through
      the Family History Research Diagnostic Criteria method and direct interviews of
      relatives with the Schedule for Affective Disorders and Schizophrenia. RESULTS:
      In our sample of psychotic patients, familial loading for psychotic disorder
      predicted persistent negative symptoms over the follow-up period (OR 1.5; 95% CI
      1-2.2), especially in schizophrenia, and was also associated with more time
      hospitalised (P < 0.05) [corrected], and more social disability at follow-up (P <
      0.05). Greater familial loading for schizophrenia predicted a greater likelihood
      of non-recovery (OR 2.2; 95% CI 1.1-4.4) and a greater likelihood to have had
      persistent negative symptoms over the follow-up period (OR 1.7; 95% CI 0.9-3.1).
      No association was found between outcome and familial loading for affective
      disorder. CONCLUSIONS: We conclude that familial loading may be a continuous risk
      factor for some dimensions of clinical outcome in the functional psychoses. This
      suggests that there is a continuum of genetic liability not only to the emergence
      of psychotic illness, but also the subsequent chronicity of the disorder.

PMID- 8733803
TI  - Seasonal changes in affective state measured prospectively and retrospectively.
AB  - BACKGROUND: The study was designed to investigate whether seasonal mood and
      behavioural changes are detectable prospectively in a non-clinical population in
      the way they have been reported in retrospective studies. The specificity of any
      seasonal fluctuation in affective state was also investigated by measuring
      anxiety as well as depression. METHOD: To measure seasonal fluctuations in affect
      and behaviour prospectively, 25 women were interviewed every month for one year
      using four scales (depression, anxiety, stress, and behavioural change).
      Retrospective accounts of mood and behaviour at the end of the year were
      collected with the Seasonal Pattern and Assessment Questionnaire (SPAQ). RESULTS:
      Seasonal depression peaked in winter as did atypical behaviour when measured
      either prospectively or retrospectively, but the difference between winter and
      summer was much more pronounced in the retrospective data. No seasonal effect was
      found for anxiety or psychosocial stressors. CONCLUSIONS: The results obtained by
      retrospective techniques have limited reliability. In the future, more
      prospective studies with unbiased, standardised instruments are recommended to
      measure seasonal variations in affect and behaviour.

PMID- 8733804
TI  - Mass hysteria: one syndrome or two?
AB  - BACKGROUND: It has been suggested that mass hysteria can be divided into two
      syndromes; one with predominant features of anxiety and the other with
      predominant abnormalities of motor behaviour. In the former condition, prior
      tension is absent and spread is by visual contact. In the latter, prior tension
      is present, initial cases can be identified and spread is gradual. METHOD: The
      development and resolution of neurological symptoms in 156 Nigerian school girls
      were studied and a diagnosis of 'mass hysteria' made. RESULTS: The signs and
      symptoms manifested by the school girls during the outbreak of illness had
      features of both 'anxiety' and 'motor' predominant forms of mass hysteria.
      CONCLUSIONS: Although there may be two patterns of symptom presentation in mass
      hysteria, other supposedly discrete features overlap. This weakens the argument
      that there are two separate syndromes.

PMID- 8733805
TI  - Validity of the Arabic version of the eating disorders inventory (EDI).
AB  - BACKGROUND: We aimed to validate the Eating Disorders Inventory (EDI) in Arabic.
      METHODS: Subjects were chosen randomly from female school students. Only healthy
      Saudi students were included. They were asked to fill the EDI and undergo a semi
      structured interview by a psychiatrist who was unaware of the EDI scores. Of 146
      students approached 12 did not meet our criteria and were excluded; 16 other
      students were excluded for incomplete responses. RESULTS: The difference between
      the two diagnostic methods in the proportion of caseness was statistically
      significantly (P < 0.0001). The scores on Perfectionism, Maturity Fears and
      Interoceptive Awareness were significantly higher in the Saudi students compared
      with Canadians (P < 0.05). CONCLUSIONS: The EDI-DT subscale has a sensitivity of
      100% and a specificity of 85%. Despite its low positive predictive value of 5%,
      it may be useful for screening large non-clinical groups for eating disorders.

PMID- 8733806
TI  - Patients' views towards care received from psychiatrists.
AB  - BACKGROUND: Measurement of the quality of psychiatric care including assessment
      of patients' views have become increasingly important as expectations of the
      standard of care rises. METHODS: Attitudes and satisfaction of acute psychiatric
      in-patients were investigated using a questionnaire looking at satisfaction,
      patients' views on personal and professional qualities of psychiatrists,
      empowerment and insight. RESULTS: The response rate was 79.2% (137 out of 173).
      Patients with a diagnosis of a non-affective psychotic illness, particularly
      those lacking insight were significantly less satisfied with their care.
      Respondents were more satisfied with the personal rather than the professional
      qualities of the doctors, and less satisfied with their empowerment and doctors'
      availability. CONCLUSIONS: In-patients' attitudes towards their psychiatric care
      involves a complex relationship between clinical and sociocultural
      characteristics. Satisfaction studies can serve as an important monitor and
      reminder of patient dissent.

PMID- 8733807
TI  - Bipolar affective disorder minus left prefrontal cortex equals schizophrenia.
AB  - BACKGROUND: An investigation of the relationship between bipolar affective
      disorder and schizophrenia, following a severe head injury and removal of the
      left prefrontal cortex. METHOD: A single case report. RESULTS: An individual with
      past history of bipolar affective disorder suffered traumatic damages to the left
      prefrontal cortex with a second lesion in the left temporal lobe. The patient
      developed typical schizophrenia nine months later. The relevance of his brain
      lesions in determining the schizophrenic symptoms is discussed. CONCLUSION: We
      propose that the specific pattern of brain injury in this patient was sufficient
      to change the phenotype from bipolar affective disorder to schizophrenia.

PMID- 8733808
TI  - Substance-induced psychosis.

PMID- 8733809
TI  - Public attitudes to mental illness.

PMID- 8733810
TI  - SSRI and sympathomimetic interaction.

PMID- 8733811
TI  - 'Psychopaths' in special hospitals.

PMID- 8733812
TI  - Use of vecuronium to prevent suxamethonium-induced myalgia after ECT.

PMID- 8733813
TI  - HIV and mental illness.

PMID- 8733814
TI  - Biological psychiatry and reductionism.

PMID- 8733815
TI  - Antipsychotic drug-induced dysphoria.

PMID- 8733816
TI  - Bias towards chronicity in schizophrenia?

PMID- 8733817
TI  - Accepting voices.

PMID- 8733818
TI  - Perspectives on treatment needs in schizophrenia.

PMID- 8733819
TI  - The treatment of negative symptoms: pharmacological and methodological issues.

PMID- 8733821
TI  - Extrapyramidal syndromes and new antipsychotic drugs: findings in patients and
      non-human primate models.

PMID- 8733820
TI  - Pre-clinical pharmacology of atypical antipsychotic drugs: a selective review.

PMID- 8733822
TI  - Positron emission tomography of in-vivo binding characteristics of atypical
      antipsychotic drugs. Review of D2 and 5-HT2 receptor occupancy studies and
      clinical response.

PMID- 8733823
TI  - ICI 204,636: a new atypical antipsychotic drug.

PMID- 8733824
TI  - Semi-quantitation of mRNA by polymerase chain reaction. Levels of oxidative
      defense enzymes and aldose reductase in rat lenses cultured in hyperglycemic or
      oxidative medium.
AB  - The high sensitivity of reverse transcriptase-polymerase chain reaction for
      detecting low copy number mRNA transcripts has been standardized to analyze the
      mRNA profiles of catalase, glutathione peroxidase, CuZn-superoxide dismutase and
      aldose reductase, with respect to the housekeeping gene cyclophilin, in rat
      lenses cultured in hyperglycemic (50mM glucose) or oxidative (100 microM H2O2)
      media for 24, 40 and 60 hr. In response to hyperglycemia mRNA expression of
      catalase appeared to be inhibited at 24 hr but attained normal levels by 40 hr.
      On the other hand, mRNA levels of catalase were higher than normal between 40 and
      60 hr in the presence of H2O2. Glutathione peroxidase mRNA abundance although
      enhanced in response to both hyperglycemia as well as H2O2-induced stress,
      displayed opposite trends with time-an increase from 24-60 hr due to
      hyperglycemia and a decrease to normal by 60 hr in the presence of H2O2. In
      contrast, CuZn-superoxide dismutase was inhibited at 50 mM glucose achieving
      baseline levels by 60 hr, while H2O2 elicited an induction at 24 hr which waned
      to basal levels by 60 hr. Interestingly, aldose reductase was unaffected by
      hyperglycemia but showed an appreciable increase with time upon exposure of the
      lens to H2O2. The role of these enzymes in cataractogenesis with regard to their
      respective mRNA levels is discussed.

PMID- 8733825
TI  - Plasma concentrations of natriuretic peptides in patients on hemodialysis.
AB  - The usefulness of plasma atrial natriuretic peptide (ANP), brain natriuretic
      peptide (BNP), C-type natriuretic peptide (CNP), and cyclic guanosine 3',5'-
      monophosphate (cGMP) as markers of fluid overload was examined in hemodialysis
      (HD) patients without diabetes mellitus. Plasma concentrations of ANP, BNP, CNP,
      and cGMP all decreased significantly during HD. Before HD, there was a strong
      correlation between plasma concentrations of ANP and those of BNP, and plasma
      concentrations of cGMP correlated significantly with those of all three
      natriuretic peptides. The cardiothoracic ratio also correlated significantly with
      plasma concentrations of ANP and those of BNP before HD. Systolic blood pressure
      correlated significantly only with plasma concentrations of CNP, both before and
      after HD. Changes in body weight during HD correlated only with those in plasma
      ANP; there was thus no correlation between changes in body weight and those in
      plasma CNP. In conclusion, only plasma ANP is a useful marker of the proper
      volume and dry weight of HD patients. Furthermore, CNP may participate in
      cardiovascular regulation in HD patients in a manner different from those of ANP
      and BNP.

PMID- 8733826
TI  - Further characterization of antagonism by alpha 2-adrenoceptor agonists of
      contractions induced by alpha 1-adrenoceptor agonists.
AB  - The population of alpha 1-adrenoceptor subtypes functionally mediating
      contraction in response to phenylephrine was examined in rat thoracic aorta and
      tail arteries. In thoracic aorta, chloroethylclonidine (CEC), which alkylates the
      alpha 1B and alpha 1D subtypes, shifted the concentration-response curve for
      phenylephrine substantially to the right without reduction in maximum
      contraction. The pA2 value (7.8) for 5-methylurapidil was consistent with the
      values reported for alpha 1D subtype, but was higher than those in tissues in
      which the alpha 1B subtype is dominant. In tail arteries, CEC did not shift the
      concentration-response curve for phenylephrine, but somewhat inhibited the
      maximum contraction. Schild analysis for 5-methylurapidil yielded a straight line
      with a slope significantly less than unity. Prazosin antagonized phenylephrine
      induced contraction of tail arteries in a competitive manner with a pA2 value of
      8.5, consistent with values for alpha 1L subtype. Clonidine relaxed the active
      tone induced by phenylephrine in both thoracic aorta and tail arteries, but quite
      different responses to clonidine by the two tissues were observed. After
      pretreatment with CEC, the relaxation induced by clonidine was abolished in
      thoracic aorta, but not in tail arteries. These results suggest that alpha 1D-and
      alpha 1L-adrenoceptors are mainly present in thoracic aorta and tail arteries,
      respectively. This difference in the populations of alpha 1-adrenoceptor subtypes
      may be related to regional differences in the modes of relaxant action of
      clonidine.

PMID- 8733827
TI  - High prevalence of antibodies to glutamic acid decarboxylase in comparison to
      islet cell antibodies in patients with long-standing insulin-dependent diabetes
      mellitus.
AB  - To elucidate the clinical significance of antibodies to glutamic acid
      decarboxylase (GAD Ab) compared to islet cell antibodies (ICA) in recent-onset
      and long-standing insulin-dependent diabetes mellitus (IDDM). We examined GAD Ab
      and ICA in 29 recent-onset and 85 long-standing patients with IDDM. GAD Ab was
      detected by a radioimmunoassay kit using purified pig brain GAD as an antigen.
      The prevalence of GAD Ab in the recent-onset diabetic patients was 55.2%,
      slightly lower than that of ICA (65.5%). In contrast, the prevalence of GAD Ab in
      long-standing diabetic patients was 42.4%, which was significantly higher than
      that of ICA (23.5%) (p < 0.01). GAD Ab were consistently detected in
      approximately 40% of patients with long-standing disease, while ICA decreased
      according to duration of disease. The GAD Ab titer in ICA-positive patients (mean
      +/- SD, 1588.2 +/- 6755.1; range, 6-38574) was significantly higher than that in
      ICA-negative patients (mean +/- SD, 13.4 +/- 17.9; and range, 5-72 units) (p <
      0.001). These findings suggest that GAD Ab are more useful than ICA to know
      participation of immune disorders in long-standing patients with IDDM.

PMID- 8733828
TI  - Pharmacokinetics and pharmacodynamics of penbutolol in healthy and cancer
      subjects: role of altered protein binding.
AB  - The pharmacokinetic and pharmacodynamic profiles of penbutolol were examined in
      healthy volunteers and in cancer patients using a pharmacokinetic/pharmacodynamic
      (pk/pd) model. After receiving a 40 mg single oral dose of penbutolol, the
      absorption rate constant, apparent volume of distribution and serum clearance of
      penbutolol were found to be reduced in the cancer group. Changes in the
      disposition of the conjugate metabolite were also observed in the cancer
      patients. Penbutolol unbound fraction in serum was statistically decreased (p <
      0.005) in the cancer group, according to the increase in the serum levels of
      alpha 1-acid glycoprotein seen in that group (p < 0.05). The pharmacodynamic
      effect of penbutolol was measured as the reduction in heart rate (HR); in healthy
      volunteers, a linear relationship (p < 0.01) between effect and penbutolol serum
      concentrations (total or unbound) was found. In contrast, in cancer patients,
      values of HR did not vary statistically in respect to baseline values. These
      results show that in cancer patients, a change in the pharmacokinetics of
      penbutolol occurs (associated with changes in drug protein binding), together
      with an alteration in the pharmacodynamics.

PMID- 8733829
TI  - Undernutrition during early lactation as an alternative model to study the onset
      of diabetes mellitus type II.
AB  - In order to characterize an alternative animal model for the study of diabetes
      mellitus type II onset, we compared the effects of a diet containing 8% of
      protein (LPD) and a normal diet containing 25% of protein supplied to the dams
      during the first 12 days of lactation. We studied in the pups the growth
      evolution and, when they develop into adults (60 days), the glucose tolerance
      test (GTT) and the insulin secretion, in response to stimulatory concentrations
      of glucose. The weight of the two groups were significantly different at 60 days
      of age (LPD = 179 +/- 19 g; NPD = 186 +/- 18 g). The GTT ten minutes after iv
      glucose administration showed a significant increase of blood glucose
      concentration of the LPD group (LPD = 550 +/- 17 mg/dl; NPD = 425 +/- 13 mg/dl, p
      < 0.001). The insulin secretion, four minutes after stimulation was found reduced
      in the LPD group (LPD = 1.1 +/- 0.08 muU/islet/min; NPD = 1.85 +/- 0.2
      muU/islet/min.). The present study indicates insulin secretory and/or resistance
      impairment due to early undernutrition. Also, the data taken together suggest
      that undernutrition during early lactation can be used as an alternative model to
      study particular characteristics of the onset of diabetes mellitus type II.

PMID- 8733830
TI  - A distinctive effect of CCCP on the transfer of erythromycin to 1-octanol: a
      possible model in promoting the intracellular antibiotic-accumulation through
      lipid in a staphylococcal cytoplasmic membrane.
AB  - Movement of erythromycin (EM), a basic antibiotic solute (pKa 8.6), in an aqueous
      buffer (pH7.6) at 37 degrees C into 1-octanol was found approximately twofold
      greater in the presence of another acidic and lipophilic solute, carbonylcyanide
      m-chlorophenylhydrazone (CCCP), when compared with the EM-movement in the absence
      of CCCP. CCCP appears to behave just like a carrier of EM, besides being a well
      known inhibitor, such as the uncoupling agent of oxidative phosphorylation. The
      probability is discussed that such an analogous event takes place in the lipid
      layers of a bacterial-cell membrane.

PMID- 8733831
TI  - Vitamin E protects against bacterial endotoxin-induced increase of plasma
      corticosterone and brain glutamate in the rat.
AB  - Plasma corticosterone (CS) and brain free aminoacids were determined in male rats
      2 hr after acute exposure to bacterial endotoxin stress BES (2.0 mg/kg i.p. of
      lipopolysaccharide, LPS). A significant increase in the levels of plasma CS and
      brain taurine (Tau), aspartate (As), glutamate (Glu), glycine (Gly) and valine
      (Val) was observed following BES. When vitamin E (alpha-tocopherol acetate AT)
      was given orally (0.25 gm/kg/day) 4 days before induction of BES, the plasma CS
      as well as the brain Glu levels were significantly reduced to the control values.
      These results indicate that plasma CS and brain Glu may be involved in the
      mechanisms by which AT protects against the neurotoxicity of BES.

PMID- 8733832
TI  - Role of iron in ricin-induced lipid peroxidation and superoxide production.
AB  - Ricin has been shown to induce oxidative stress in the livers of mice in vivo.
      These studies examined ricin-induced hepatic microsomal lipid peroxidation in
      mice, and the modulation thereof by iron and desferrioxamine. In addition, the
      studies investigated the production of superoxide anion by microsomes,
      mitochondria, and macrophages. Ricin (25 micrograms/kg, in vivo) increased
      microsomal lipid peroxidation by approximately 1.8-fold relative to control
      animals. This effect was abrogated by adding desferrioxamine to the microsomes.
      Fe2+ increased lipid peroxidation approximately 15-fold and 5-fold when added to
      microsomes from control and ricin-treated animals, respectively. Adding ricin to
      microsomes from control animals, however, decreased lipid peroxidation in a
      concentration-dependent manner. Desferrioxamine decreased lipid peroxidation by
      47% and 64% in the absence and presence of ricin (5 micrograms/ml), respectively.
      Ricin, added to mitochondria from untreated animals decreased lipid peroxidation
      by 26% and 17% in the presence and absence of Fe2+, respectively. The
      administration of ricin (5 and 25 micrograms/kg) to mice increased microsomal,
      mitochondrial and macrophage superoxide anion production, in a dose-dependent
      fashion. The results suggest that iron mediated production of superoxide anion
      may be involved in the process of oxidative stress induced by ricin.

PMID- 8733833
TI  - Relative gold-binding capacity of metallothionein: studies in renal cytosols of
      gold-injected rats.
AB  - To determine the gold-binding capacity of metallothionein (MT) in cytosols of
      gold-injected rats, we examined the relationship between gold contents in
      cytosols and in MT fraction in rat kidneys. Each rat was injected
      intraperitoneally once with 0.9% NaCl or gold (5, 10 or 20 mg gold/kg b.w.). The
      gold contents in kidneys and in MT fraction increased following the injected
      amount of gold. The distribution profiles of the renal cytosols of gold-injected
      rats on a Sephadex G-75 column showed that the amount of the increased gold was
      attributable to the high molecular weight proteins (HP) and the MT fractions.
      There were close relationships between the gold contents in cytosol and in MT
      fractions, and between the gold contents in cytosol and in HP fractions. These
      results demonstrate that 14% of the increased gold in the renal cytosols of gold
      injected rats was bound to MT and that 79% of the increased gold was bound to HP.
      Our results suggest that the role of metallothionein in gold accumulation in
      kidneys is different from that in zinc accumulation in kidneys.

PMID- 8733834
TI  - Second eye surgery: the benefit to functional activity.

PMID- 8733835
TI  - Preventing iris capture.

PMID- 8733836
TI  - Epithelial inclusion cyst.

PMID- 8733837
TI  - Realistic refractive results.

PMID- 8733838
TI  - Decentration of plate-haptic lenses.

PMID- 8733839
TI  - Consultation section. Positive Seidel test post-cataract surgery.

PMID- 8733840
TI  - Extracapsular cataract extraction and intraocular lens implantation in eyes
      filled with silicone oil.
AB  - Extracapsular cataract extraction with posterior chamber intraocular lens
      implantation was performed in five phakic eyes filled with silicone oil following
      vitreoretinal surgery. Silicone oil migration was prevented during surgery using
      an anterior chamber maintaining system and a self-sealed corneoscleral tunnel
      incision. The posterior capsule opacified within 3 months in all patients, and
      neodymium:YAG capsulotomy or surgical discission was performed in a diamond
      shaped pattern. No silicone-related complications were found, including silicone
      oil migration into the anterior chamber. There were no difficulties visualizing
      the peripheral retina during funduscopy.

PMID- 8733841
TI  - A high-stability, one-stitch W incision for cataract surgery.
AB  - We describe a technique to create a highly stable, one-stitch incision for use
      with rigid posterior chamber intraocular lenses (IOLs). Inverse U and W incisions
      are compared in 203 consecutive eyes with 3 months follow-up. A scleral groove
      resembling an inverted W is dissected away from the limbus, and the anterior
      chamber is entered by a conventional tunnel technique that resembles a frown
      incision but has an additional triangular, central scleral flap. When the
      incision is closed, a single stitch is placed through the flap, away from the
      limbus. Advantages of the W incision include reduction and control of
      astigmatism, improved self-sealing, reduced postoperative leakage, no special
      suture-material requirements, high mechanical stability, easy extendability for
      extracapsular cataract extraction or trabeculectomy, and intraoperative sealing
      of a leaking irrigation/aspiration opening by inverting the flap. The W incision
      offers high stability and multiple advantages over the frown incision and is
      suitable for use with rigid posterior chamber IOLs.

PMID- 8733842
TI  - Re-forming the flat anterior chamber with Healon.
AB  - A shallow or flat anterior chamber may occur after complicated cataract surgery,
      a filtering procedure for glaucoma, or combined surgery. We describe a technique
      for injecting sodium hyaluronate (Healon) into the anterior chamber through the
      previous paracentesis tract in the operating room or at the slitlamp microscope.
      Re-forming the anterior chamber with Healon may pre-empt the anatomical sequelae
      of prolonged anterior chamber shallowing and prevent the need for more invasive
      surgery.

PMID- 8733843
TI  - First results of cataract surgery and implantation of negative power intraocular
      lenses in highly myopic eyes.
AB  - OBJECTIVES: To determine whether cataract surgery in highly myopic eyes should be
      considered high-risk surgery and whether exact intraocular lenses (IOLs) should
      be implanted if negative power is required. SITE: Klinik Dardenne, Bonn-Bad
      Godesberg, Germany. METHOD: We retrospectively studied 32 eyes of 27 highly
      myopic patients who had cataract surgery and posterior chamber IOL implantation.
      Intraocular lens power varied from -1.0 to -8.0 diopters (D), and eye length
      varied from 31.0 mm to more than 35.0 mm. Follow-up ranged from 6 to 36 months.
      Patients were analyzed for postoperative visual acuity and for intraoperative and
      postoperative complications. RESULTS: No patients experienced intraoperative
      complications. Posterior capsule opacification, which occurred in 14 eyes, was
      the only postoperative complication in the anterior or posterior segments. Ninety
      four percent of eyes achieved improved best corrected visual acuity, and 69% of
      eyes were within 1.0 D of the refractive target. CONCLUSIONS: Cataract surgery
      can be performed in highly myopic eyes without intraoperative complications. A
      posterior chamber IOL should be implanted for postoperative refraction and
      intraocular stability, even if negative lens power is required.

PMID- 8733844
TI  - Evaluating data acquisition and smoothing functions of currently available
      videokeratoscopes.
AB  - PURPOSE: To compare the accuracy of computerized videokeratography systems using
      identical, calibrated test objects. SETTING: Lions Eye Institute, Albany, New
      York. METHODS: We evaluated the accuracy and smoothing of raw data acquisition
      (axial solution) of seven commercially available videokeratoscopes: Alcon EyeMap,
      Computed Anatomy TMS, EyeSys CAS, Humphrey MasterVue, Topcon CM-1000, Optikon
      Keratron, and TechnoMed C-Scan. We used six calibrated test objects to simulate
      clinical settings: spherical, spherocylindrical, simulated myopic ablation,
      hyperopic ablation, and a simulated central island. RESULTS: None of the systems
      accurately imaged all objects. Although all systems imaged spherical objects with
      reasonable accuracy, errors greater than 4.0 diopters (D) frequently occurred in
      the central 6.0 mm optical zone (maximum error 10.0 D) Sources of error included
      excessive raw data smoothing, inability to read large transitions, loss of
      accuracy in the periphery, and poor central coverage. CONCLUSION: The clinician
      should be aware of the potential limitations of corneal topography when making
      clinical decisions.

PMID- 8733845
TI  - Corneal topographic changes after noncontact holmium:YAG laser thermal
      keratoplasty to correct hyperopia.
AB  - PURPOSE: To analyze the changes in corneal curvature induced by laser thermal
      keratoplasty (LTK) to correct hyperopia. SETTING: Cullen Eye Institute, Baylor
      College of Medicine, Houston, Texas. METHODS: We performed LTK on nine hyperopic
      eyes using a noncontact holmium: YAG (Ho:YAG) laser. Five eyes received a single
      ring of eight spots at the 6 mm zone (Group A); four received a second ring of
      eight at the 7mm zone (Group B). Computerized videokeratography (CVK) was
      obtained preoperatively and 1, 30, 90, 180, and 360 days postoperatively. We
      calculated the net dioptric changes in the following CVK values: corneal
      curvature at the 1, 3, 5, and 7 mm zones; effective corneal refractive power (Eff
      RP); and spherical equivalent of subjective manifest refraction (SE SMR). We
      classified difference maps according to the pattern of induced change. RESULTS:
      At 1 year, steepening at the 1, 3, 5, and 7 mm CVK zones was 0.5 diopter (D), 0.6
      D, 0.1 D, and -0.42 D, respectively, in Group A and 1.5 D, 1.5 D, 1.1 D, and 0.54
      D, respectively, in Group B. Effective corneal refractive power increased 0.6 D
      in Group A and 1.5 D in Group B. Mean change in SE SMR was -0.6 D in Group A and 
      1.4 D in Group B. Most regression occurred during the first 90 days. Difference
      maps showed five bow-tie, two irregularly irregular, one semicircular, and one
      homogeneous patterns. CONCLUSIONS: Noncontact Ho:YAG LTK produced peripheral
      corneal flattening and central corneal steepening. A greater change in curvature
      was produced using a two-ring treatment.

PMID- 8733846
TI  - Excimer laser photorefractive keratectomy using an erodible mask to treat myopic
      astigmatism.
AB  - PURPOSE: To evaluate the results of excimer laser photorefractive keratectomy
      (PRK) using an erodible mask to treat myopic astigmatism. SETTING: Douglas
      Memorial Hospital Medical Centre, Fore Erie, Ontario, Canada. METHODS:
      Photorefractive keratectomy was done on 25 consecutive eyes of 25 patients with
      myopic astigmatism using the OmniMed excimer laser and a compound single-use
      myopic erodible mask manufactured to produce a specific spherical and cylindrical
      correction for each individual patient. Follow-up ranged from 6 months for 25
      patients to 1 year for 5 patients. RESULTS: Six months after PRK, the mean
      preoperative sphere of -7.46 diopters (D) decreased to -0.17 D and the mean
      preoperative cylinder of 2.31 D dropped to 0.69 D; 73% of astigmatism was
      corrected. In the five eyes followed for 1 year, 94% of astigmatism was
      corrected. Correction of the myopic component was less predictable, with a wider
      than anticipated range of overcorrection. CONCLUSIONS: Excimer laser PRK
      successfully corrected myopic astigmatism in patients with low and high myopia.
      The less predictable myopia results may have been secondary to increased
      procedure time, corneal dehydration, and difficulty in patient fixation and thus
      alignment.

PMID- 8733847
TI  - Improved stereoacuity: an indication for unilateral cataract surgery.
AB  - PURPOSE: To determine whether stereoacuity is an objective indicator of
      functional improvement following unilateral cataract surgery. SETTING: Department
      of Opthalmology, Loyola University Chicago, Maywood, Illinois. METHODS: Seventeen
      consecutive patients with unilateral cataracts (8 pseudophakic, 9 phakic in
      contralateral eye) were studied prospectively. Best corrected distance visual
      acuity in the eye with cataract ranged from 20/40 to 20/400. Distance acuity in
      the eye without cataract was 20/20 or 20/25. All patients had cataract surgery
      with posterior chamber intraocular lens implantation. Stereoacuity was measured
      preoperatively and postoperatively; at near by Titmus test (TT) and at distance
      by B-VAT BVS random dot E (BVRDE) and contour circles (BVC). Nonparametric
      Spearman rank correlation and Wilcoxon rank tests were used for analysis.
      RESULTS: Preoperatively, reduced near visual acuity in the cataractous eye
      correlated with reduced near stereo (TT), r = .6, P = .01. Postoperatively, near
      stereoacuity improved in all but one patient, from a median of 200 seconds of arc
      (sec arc) to 40 sec arc (P = .004); distance stereoacuity improved in all but two
      patients from a median of unrecordable to 120 sec arc (BVC) (P = .006).
      Preoperatively none of the patients could see the largest distance BVRDE target,
      whereas postoperatively 4 of 17 had BVRDE stereoacuity of 120 to 240 sec arc (P =
      .06). CONCLUSIONS: Patients with unilateral cataracts have reduced stereoacuity,
      correlating with their reduced monocular visual acuity. In this study, distance
      and near stereoacuity improved postoperatively. Decreased stereoacuity may
      provide an indication for unilateral cataract surgery.

PMID- 8733848
TI  - Comparison of a diffractive bifocal and a monofocal intraocular lens.
AB  - PURPOSE: To compare a Pharmacia diffractive bifocal intraocular lens (IOL) with a
      monofocal lens of the same design without the diffractive grating. SETTING:
      Multicenter study. METHODS: This randomized, prospective study comprised 70
      patients with a monofocal IOL and 79 with a diffractive bifocal IOL. Follow-up
      was 5 to 6 months. Near and distance visual acuities, contract sensitivity,
      patient satisfaction, and spectacle use were evaluated. RESULTS: All patients
      achieved a best corrected visual acuity of 0.5 or better; 80% in the monofocal
      and 71% in the bifocal group had a best corrected visual acuity of 1.0 or better.
      Without correction, 93% of the bifocal and 9% of the monofocal group could read
      J3 or better. With distance correction, 99% and 4%, respectively, could read J3
      or better. Contrast sensitivity was slightly lower in the bifocal group at
      distance and near for all spatial frequencies. In the bifocal group, 46% never
      used spectacles for near tasks. Overall satisfaction was rated good by 86% of the
      monofocal and 85% of the bifocal group. CONCLUSIONS: The diffractive bifocal IOL
      performed well at distance and near. Patients who no longer require spectacles
      will benefit significantly from a bifocal IOL, but many with a bifocal IOL in one
      eye will require spectacles for the fellow eye.

PMID- 8733849
TI  - Visual significance of glistenings seen in the AcrySof intraocular lens.
AB  - PURPOSE: To investigate the visual significance of "glistenings" in acrylic
      intraocular lenses (IOLS). SETTING: John Moran Eye Center, University of Utah,
      Salt Lake City. METHODS: Seventeen patients who had phacoemulsification with
      implantation of the AcrySof acrylic IOL were evaluated by slitlamp examination
      and visual acuity, contrast sensitivity, and glare testing. Ten patients had a
      silicone posterior chamber IOL in the opposite eye and had testing with similar
      visual parameters for comparison. Glistenings noted in the acrylic IOLs were
      graded at the slitlamp. Laboratory analysis of five acrylic IOLs was also done to
      reproduce the glistenings noted clinically. RESULTS: All 17 patients with the
      acrylic IOLs had some lenticular glistenings, ranging from trace to 2+.
      Statistical analysis of visual acuity, contrast sensitivity, and glare testing
      revealed a statistically significant difference between the acrylic and the
      silicone IOLs only in contrast sensitivity. Laboratory analysis of the acrylic
      IOLs showed similar glistenings from 48 to 72 hours after they were placed in
      balanced salt solution. CONCLUSIONS: A patients who received AcrySof IOLs that
      came in the AcryPak had some degree of glistenings. There was also a significant
      decrease in contrast sensitivity compared with that of fellow eyes with silicone
      IOLs. The glistenings are likely caused by water vacuoles that form within the
      lens after hydration within the eyes. Further studies are necessary to assess the
      exact cause of these glistenings.

PMID- 8733850
TI  - Posterior capsulorhexis in adult eyes with intact and clear capsules.
AB  - PURPOSE: To evaluate the feasibility and risks of primary posterior
      capsulorhexis. SETTING: Department of Ophthalmology, University Hospital of
      Liege, Belgium. METHODS: Retrospective analysis of 319 patients with cataracts
      who had phacoemulsification or manual extracapsular cataract extraction with a
      simultaneous circular posterior capsulorhexis between August 1993 and April 1994.
      The number of intraoperative complications and the number of postoperative
      complications that could be related to the posterior capsule opening were looked
      at. Fluorescein angiography was performed in a random sample of patients.
      RESULTS: Twelve intraoperative complications consisted of 5 irregular tears, 4
      vitreous prolapses into the posterior capsulorhexis, and 3 vitreous prolapses
      into the anterior chamber; 11 occurred in eyes with positive posterior pressure.
      Postoperative complications consisted of 3 vitreous prolapses into the pupil and
      1 retinal detachment. Two of the 3 late vitreous prolapses occurred in eyes in
      which the posterior capsulorhexis was larger than the intraocular lens (IOL)
      optic. The retinal detachment occurred in an eye with a 25.79 mm axial length.
      Fluorescein angiography of 49 cases revealed 3 with cystoid macular edema.
      CONCLUSIONS: Based on our results, we believe that primary posterior
      capsulorhexis can be a routine procedure during cataract surgery and IOL
      implantation in adults, except in cases of positive pressure. The diameter of the
      posterior capsulorhexis should be smaller than the diameter of the IOL optic.

PMID- 8733851
TI  - Combined endocapsular phacoemulsification, pars plana vitrectomy, and intraocular
      lens implantation.
AB  - OBJECTIVE: To determine whether a combined vitrectomy and phacoemulsification is
      a safe and feasible approach in patients requiring a vitrectomy who have a
      concomitant significant lens opacity. SETTING: Royal Victoria Eye and Ear
      Hospital, Dublin, Ireland. METHODS: This retrospective study comprised five
      patients with significant lens opacities who had combined trans pars plana
      vitrectomy and phacoemulsification with intraocular lens implantation. Main
      outcome measures were visual acuity and intraoperative and postoperative
      complications. RESULTS: The combined surgical approach resulted in minimal
      complications, and postoperative visual acuity was satisfactory. CONCLUSION: In
      the hands of experienced phacoemulsification and vitrectomy surgeons, combined
      trans pars plana vitrectomy and phacoemulsification can be a safe approach in
      treating patients requiring a vitrectomy who have significant lens opacities
      precluding a view of the posterior segment.

PMID- 8733852
TI  - Combined phacoemulsification, intraocular lens implantation, and trabeculectomy.
AB  - PURPOSE: To analyze the results of phacoemulsification and posterior chamber
      intraocular lens (IOL) implantation combined with trabeculectomy. SETTING: John
      Moran Eye Center, University of Utah, Salt Lake City. METHODS: Two hundred twelve
      eyes of 174 patients with glaucoma and cataracts were analyzed retrospectively
      after cataract removal by phacoemulsification with posterior chamber IOL
      implantation combined with trabeculectomy. RESULTS: With an average follow-up of
      26 months, patients had a significant improvement in visual acuity. The
      preoperative mean intraocular pressure (IOP) of 23.1 mm Hg decreased
      postoperatively to 15.9 mm Hg. Mean number of glaucoma medications decreased from
      1.85 preoperatively to 0.41 postoperatively. Twenty-one patients (10% had a
      postoperative IOP of greater than 21 mm Hg, and seven required trabeculectomy
      revisions. CONCLUSION: Combined phacoemulsification, posterior chamber IOL
      implantation, and trabeculectomy yielded excellent results in the treatment of
      patients with both cataract and glaucoma.

PMID- 8733853
TI  - Intraocular availability and pupillary effect of flurbiprofen and indomethacin
      during cataract surgery.
AB  - PURPOSE: To compare the bioavailability and pupillary effect of flurbiprofen and
      indomethacin during phacoemulsification and intraocular lens implantation.
      SETTING: Gimbel Eye Centre, Calgary, Alberta, Canada. METHODS: In this
      prospective, randomized, double-masked study, 236 patients had cataract
      extraction by phacoemulsification and posterior chamber intraocular lens
      implantation. They received topical flurbiprofen 0.03% solution or indomethacin
      1% suspension applied every 15 minutes for 60 to 75 minutes before surgery. An
      aqueous humor sample (100 microL) was taken immediately before the corneal
      incision was made. Pupil diameters (horizontal and vertical) were measured before
      aqueous humor sampling, after phacoemulsification, after irrigation and
      aspiration (I/A), and after acetylcholine instillation. RESULTS: Mean
      concentration of flurbiprofen and indomethacin in the aqueous humor was 59.8
      ng/mL and 90.2 ng/mL, respectively (P < .001). The percentage of dose detected in
      the aqueous humor was 4.38% in the flurbiprofen group and 0.21% in the
      indomethacin group (P < .001). Pupil diameters were 7.2 and 7.3 mm presurgery and
      7.0 and 7.0 mm after I/A in the flurbiprofen and indomethacin groups,
      respectively (P > .05). No adverse events were reported in either group.
      CONCLUSIONS: Although the absolute concentration of indomethacin was higher, the
      percentage of dose detected in the aqueous humor was 20 times greater in the
      flurbiprofen than in the indomethacin group. Flurbiprofen is absorbed 20 times
      more readily than indomethacin. Both drugs were equally effective in preventing
      miosis during cataract surgery.

PMID- 8733854
TI  - Topical versus peribulbar anesthesia in clear corneal cataract surgery.
AB  - PURPOSE: To evaluate the efficacy of topical anesthesia as an alternative to
      peribulbar anesthesia in clear corneal cataract surgery. SETTING: Department of
      Ophthalmology, University of Vienna, Austria. METHODS: In this prospective,
      double-blind clinical trial, 36 patients had bilateral cataract surgeries
      performed from 1 to 3 months apart. Half of the patients had topical anesthesia
      for the first surgery and peribulbar anesthesia for the second surgery. The other
      half had peribulbar first and then topical. All surgery was done using a temporal
      clear corneal approach and bimanual phacoemulsification followed by in-the-bag
      intraocular lens implantation. Subjective pain was assessed using a visual analog
      scale of no pain (0%) to worst pain imaginable (100%) and intraoperative motility
      using a rank scale of adverse motility (-5) to ideal patient cooperation (+5).
      RESULTS: Subjective pain was comparable whether topical or peribulbar anesthesia
      was used (mean 10.75 versus 10.97%; P > .6). Patient cooperation (motility) was
      significantly better when topical anesthesia was used (+2.16 versus +1.11; P =
      .03). There were no significant differences in complications. A peribulbar block
      was given in addition to the topical anesthesia in two cases. CONCLUSIONS:
      Topical anesthesia is a safe, effective alternative to peribulbar anesthesia in
      clear corneal cataract surgery.

PMID- 8733855
TI  - Neodymium:YAG laser lens ablation in a rabbit model.
AB  - PURPOSE: To assess the safety of neodymium:YAG (Nd:YAG) laser lens ablation in a
      rabbit model prior to human investigation. METHODS: The Nd:YAG laser lens
      ablation probe was inserted into the anterior chamber of 14 New Zealand white
      rabbit eyes and Nd:YAG laser lens ablation was simulated, exposing the eyes to
      energy significantly higher than that used in previous experimental Nd:YAG lens
      ablation of the human crystalline lens. After the procedure, the rabbits were
      killed at 1 hour, 1 day, or 1 week and the eyes evaluated by specular microscopy,
      ultrasonic pachymetry, and light microscopy. RESULTS: There was no statistically
      significant difference in the postoperative endothelial cell counts or ultrasonic
      pachymetry of study eyes and control (unoperated) eyes. Light microscopy revealed
      no apparent damage to the cornea, trabecular meshwork, or retina of the study
      eyes. CONCLUSIONS: the Nd:YAG laser lens ablation device appears to be a safe
      method of cataract removal in this animal model. Further study is needed to
      determine the safety and efficacy of this device for cataract removal in humans.

PMID- 8733856
TI  - Endothelial changes following refractive surgery.

PMID- 8733857
TI  - Calculating intraocular lens power in eyes with keratoconus using
      videokeratography.
AB  - A patient with keratoconus had cataract extraction and intraocular lens (IOL)
      implantation in both eyes. The IOL power was determined using keratometric values
      (K-values) measured by standard keratometry in the right eye and
      videokeratography in the left eye. The ideal IOL power and the K-value that would
      have led to the ideal IOL power were determined from the postoperative refraction
      at 6 weeks. The ideal K-value was compared with the K-values derived from
      videokeratography and standard keratometry. Refraction at 6 weeks postoperatively
      was 5.60 and 1.00 diopter more myopic than the aim in the right and left eye,
      respectively. The mean power in ring 3 in videokeratography of the left eye was
      the same as the ideal K-value calculated using the Holladay formula. Determining
      IOL powers with videokeratography-derived K-values might be more accurate than
      standard keratometry in patients with keratoconus.

PMID- 8733858
TI  - Epikeratophakia to correct traumatic aphakia after penetrating keratoplasty.
AB  - A 19-year-old man with keratoconus sustained ocular trauma and became aphakic in
      his operated left eye 2 months after penetrating keratoplasty. Original corneal
      wound repair was performed without intraocular lens implantation. Attempts to
      correct his aphakia with a contact lens failed when the patient became intolerant
      to its use. As an alternative, the patient had elective epikeratophakia. A
      standard 8.5 mm lenticule was placed over existing corneal graft. This operation
      resulted in +12.25 diopters of correction and a best corrected visual acuity of
      20/25 at 30 months postoperatively. There was no sign of abnormalities at the
      host cornea or the transplanted lenticule. This case indicates that
      epikeratophakia may be successfully performed over existing corneal grafts.

PMID- 8733859
TI  - Ocular deviation following excimer laser photorefractive keratectomy.
AB  - We present a case of ocular deviation and diplopia that developed 9 months after
      monocular excimer laser photorefractive keratectomy. In this case, decompensation
      occurred because of a breakdown of fusion at distance. We suggest a cover test to
      assess the presence of significant phorias in all candidates for refractive
      surgery procedures.

PMID- 8733860
TI  - Aortic reconstruction in kidney transplant recipients.
AB  - Renal transplantation has increased the longevity of patients with uremia. An
      increasing number undergo aortic reconstruction, which exposes the transplanted
      kidney to ischemic injury. To evaluate the risk for renal failure, loss of the
      transplant, and methods of renal protection, we reviewed our experience. Clinical
      data were reviewed for 10 consecutive patients (7 men, 3 women; mean age 52.7
      years [range 32 to 75 years]) with a transplanted kidney who underwent aortic
      reconstruction between 1977 and 1994 at our institution. Mean interval between
      renal transplantation and aortic reconstruction was 5.9 years (range 1 month to
      12.7 years). Seven patients required emergency repair because of dissection (2
      patients), aneurysm rupture (4 patients), or symptomatic aneurysm (1 patient);
      three underwent elective repair. Reasons for reconstruction included aortic
      dissection (2 patients), aneurysm of the descending thoracic (2 patients),
      thoracoabdominal (1 patient), or abdominal aorta (3 patients), and aortoiliac
      occlusive disease (2 patients). Patients with thoracic or thoracoabdominal
      reconstructions underwent repair with atriofemoral, aortofemoral, or
      femorofemoral shunt placement or bypass. Of the five abdominal aortic
      reconstructions, the kidney was protected with aortofemoral shunt placement in
      one patient and cold renal perfusion in three. In two of them, topical cooling of
      the kidney also was used. One patient with acute aortic dissection died at 39
      days as a result of respiratory failure. Loss of the recently transplanted kidney
      was caused by acute rejection. One patient had a transient increase in serum
      creatinine concentration. Eight no worsening of renal function, and none of the
      nine survivors lost the transplanted kidney. We concluded that aortic
      reconstruction can be safely performed in kidney transplant recipients. Patients
      in whom thoracic or thoracoabdominal aortic reconstruction was required were
      protected with an atriofemoral or aortofemoral bypass or shunt. Patients
      undergoing abdominal aortic reconstruction did well when cold renal perfusion
      with or without local cooling of the transplant was used for renal protection.
      Transplanted kidneys appeared to tolerate ischemic injury similarly to native
      kidneys.

PMID- 8733861
TI  - Comparison of spiral CT scan and arteriography for evaluation of renal and
      visceral arteries.
AB  - Renal and visceral artery images obtained concurrently with spiral CT and
      conventional arteriography were compared for 32 patients. Indications for imaging
      were occlusive disease (n = 12), aneurysmal disease (n = 9), and renal or
      visceral artery disease (n = 11). Conventional arteriography enabled
      visualization of 64 renal arteries and 15 accessory renal arteries. Lateral
      aortograms obtained in 15 patients enabled visualization of 14 superior
      mesenteric (SMA) and 14 celiac arteries. Spiral CT enabled visualization of 60
      renal arteries, 12 accessory renal arteries, 27 SMAs, and 22 celiac arteries.
      Calcification or a disparity in timing of contrast material injection and
      scanning prevented visualization of the celiac artery in 10 patients and the SMA
      in four patients. With conventional arteriography as the standard for comparison,
      spiral CT had a sensitivity of 67% and a specificity of 95% for depiction of at
      least 75% stenosis in the main renal artery. By means of the Pearson correlation
      coefficient, significant correlation (p < 0.001) was confirmed between spiral CT
      and arteriography for evaluation of stenosis of the main renal artery, SMA, and
      celiac artery. This early experience suggests that spiral CT may be useful in
      evaluation of renal and visceral arteries and their relationship to aortic
      disease.

PMID- 8733862
TI  - Outcomes in the management of vascular prosthetic graft infections confined to
      the groin: a reappraisal.
AB  - The management of vascular prosthetic graft infections confined to the groin
      continues to be controversial. To critically evaluate this problem, we reviewed
      the records of our vascular registry from December 1992 through February 1995 and
      found 17 incidences of groin sepsis involving a vascular prosthesis in 10
      patients. These included a proximal prosthetic femoropopliteal bypass (n = 6), an
      aortobifemoral graft limb (n = 5), an ileofemoral bypass (n = 3), a prosthetic
      femoral patch (n = 2), and an aortofemoral/femorofemoral bypass (n = 1). The mean
      age of these patients was 65 years. Six patients were diabetic, four were on
      systemic steroids, and two were diabetic and on steroids. All infections were
      Szilagyi grade III including three in which the patients presented with local
      hemorrhage. Treatment consisted of irrigation, radical debridement with or
      without in situ graft replacement, and local rotational muscle flap coverage in
      nine cases, graft excision with extra-anatomic (obturator ileofemoral bypass)
      graft replacement in six cases, and excision alone in two cases. Of the 17
      infections treated operatively and followed from 1 week to 18 months (median 5
      months), eight (47%) showed no evidence of recurrence, six (35%) recurred, two
      (12%) caused early death, and one resulted in a thrombosed graft requiring extra
      anatomic reconstruction. Of the nine infected grafted treated locally with muscle
      flaps, six showed recurrent infection from 3 weeks to 15 months and one
      thrombosed for a total local treatment failure rate of 78%. Only two grafts are
      free of infection at 4 and 5 months, respectively. Of the six incidences of
      infection treated with obturator bypass, four (66%) are free of infection and two
      resulted in patient death; both infections treated with excision alone were
      eradicated but resulted in a major lower extremity amputation. These data
      question the growing acceptance of debridement and local muscle flap coverage for
      the treatment of all prosthetic vascular graft infections confined to the groin,
      especially in patients who are diabetic or on systemic steroids.

PMID- 8733864
TI  - Results of contemporary surgical treatment of descending thoracic aortic
      aneurysms: experience in 198 patients.
AB  - Between April 1987 and March 1995, 198 patients (133 males [67.17%] and 65 female
      [32.83%]; mean age 63.85 years) underwent descending thoracic aortic aneurysm
      repair. Of these, 142 patients (71.71%) had symptoms. In most patients (n = 123
      [62%]) the aneurysmal disease was extensive, involving at least two thirds of the
      descending aorta. In 153 patients (77.27%), the repair was completed with the
      simple clamp technique (mean clamping time 24.6 minutes). Left atrium-to-femoral
      bypass was used in 26 patients (13.13%) at high risk (mean clamping time 37.4
      minutes). Profound hypothermia and circulatory arrest were necessary in 19
      patients (9.6%) with extensive aneurysms that involved the arch and ascending
      aorta (mean circulatory arrest time 46 minutes). Operative mortality was 5.1% (n
      = 10). The causes of death were cardiac in three patients (1.5%), pulmonary in
      four (2.0%), and renal in three (1.5%). Postoperative paraplegia occurred in
      three patients (1.5%). Important predictors (p < 0.05) of mortality at regression
      analysis included renal failure, pulmonary complications, and paraplegia. The
      only independent predictor of paraplegia was clamping time. In conclusion, the
      simple clamp procedure remains the technique of choice in the majority of
      patients with descending aortic aneurysms. Atriofemoral bypass is an important
      adjunct in patients at high risk.

PMID- 8733863
TI  - Normothermic renal artery perfusion: a comparison of perfusates.
AB  - Hypothermia and preservative perfusates have been used to decrease ischemic renal
      injury. This study was performed to identify the preservative function of
      perfusates independent of the effects of hypothermia. Rats underwent 45 minutes
      of renal ischemia. Rectal and renal parenchyma temperatures were monitored and
      maintained within 1 degree C of normal. Perfusates were University of Wisconsin
      solution (UW), Euro-Collins solution, normal saline solution, and Ringer's
      lactate solution. A nonperfused ischemic control and a nonischemic control group
      were also evaluated. Parameters evaluated included serum creatinine and blood
      urea nitrogen levels, renal ischemic injury grade, renal weight, and gross
      appearance of the injured kidney. Rats treated with UW solution were found to
      have a significantly lower creatinine, blood urea nitrogen, and injury grade than
      the other three perfused groups. The external gross appearance of the UW-treated
      kidneys was normal, whereas that of the other groups demonstrated moderate to
      severe injury. Although the mean right/left renal weight difference of the UW
      treated group was lower than that of the other three groups, this was not
      statistically significant. Under normothermic conditions in rats, UW solution
      affords significant renal protection from ischemia. Euro-Collins, normal saline,
      and Ringer's lactate solutions display no significant protective effect.

PMID- 8733865
TI  - Perioperative morbidity and mortality in combined vs. staged approaches to
      carotid and coronary revascularization.
AB  - Between 1986 and 1994 we identified 57 patients who underwent carotid
      endarterectomy (CEA) and coronary artery bypass grafting (CABG) during the same
      hospitalization. Simultaneous CABG and CEA was performed in 28 patients (mean age
      70.5 years, 58% male). Indications for CABG in these patients were myocardial
      infarction in two crescendo angina in 19, congestive heart failure in two and
      left main or triple-vessel coronary artery disease noted during carotid
      preoperative evaluation in five. Indications for CEA were transient ischemic
      attack (TIA) in 12, crescendo TIA in six, cerebrovascular accident (CVA) in five,
      and asymptomatic stenosis in five. There were no postoperative myocardial
      infarctions or perioperative deaths. Two patients developed atrial fibrillation,
      and four patients had CVAs (two were ipsilateral to the side of CEA). Twenty-nine
      patients underwent staged procedures (i.e., not performed concomitantly but
      during the same hospitalization). Indications for CABG and CEA were comparable to
      those in the group undergoing simultaneous procedures. In 17 patients CEA was
      performed before CABG. There was a single CVA, the result of an intracerebral
      hemorrhage. Five of the 17 patients had a myocardial infarction and two died; one
      patient had first-degree heart block requiring a pacemaker. Four additional
      patients developed atrial fibrillation, one of whom required cardioversion. The
      remaining 12 patients had CABG followed by CEA. There were no CVAs, myocardial
      infarctions, arrhythmias, or deaths in this subgroup. These data demonstrate that
      the performance of simultaneous CABG and CEA procedures is associated with
      increased neurologic morbidity (14.3%), both ipsilateral and contralateral to the
      side of carotid surgery in contrast to staged CABG and CEA (3.4%). In addition,
      when staged carotid surgery preceded coronary revascularization in those with
      severe coronary artery disease, the combined cardiac complication and mortality
      rate was significantly higher than when coronary revascularization preceded CEA.
      This evidence suggests that when CABG and CEA must be performed during the same
      hospitalization, the procedures should be staged with CABG preceding CEA.

PMID- 8733866
TI  - Safety and cost-efficiency of 24-hour hospitalization for carotid endarterectomy.
AB  - The safety and cost savings of carotid endarterectomy (CEA) were determined with
      guidelines developed after vascular "critical pathways" were implemented. Using
      these guidelines, our goal was to admit patients the day of surgery and to
      discharge them the next morning. Morbidity, mortality, readmission rates, same
      day admissions, duration of stay, and hospital costs were compared between
      patients undergoing CEA who were electively admitted between September 1, 1992
      and August 31, 1993 (group 1) and January 1, 1994 and March 31, 1995 (group 2).
      Between these two time periods, vascular critical pathways were instituted and
      all preoperative examinations were performed on an outpatient basis. The majority
      of CEAs were performed with the patient under general anesthesia. We found no
      significant differences between group 2 (n = 68) vs. group 1 (n = 40) in terms of
      mortality (1.5% [1 of 68] vs. 2.5% [1 of 40]), cardiac events (2.9% [2 of 68] vs.
      2.5% [1 of 40]), neurologic events (2.9% [2 of 68] vs. 2.5% [1 of 40]), or
      readmission rate (1.5% [1 of 68] vs. 0% [0 of 40]). Same-day admissions were
      significantly higher (94% [64 of 68] vs. 5% [2 of 40]; p < 0.0001), and average
      duration of stay was significantly lower (1.3 vs. 5.1 days; p < 0.0001) in group
      2 vs. group 1, respectively. Hospital charges were decreased by $5510 per patient
      in group 2. We conclude that hospital costs can be significantly reduced for most
      patients undergoing CEA when they are admitted on the day of surgery and
      discharged the following morning, with no negative impact on morbidity and
      mortality.

PMID- 8733867
TI  - Transgraft infusion of heparin to prevent early thrombosis of expanded PTFE
      grafts in canine femoral veins.
AB  - Recently we designed an expanded polytetrafluoroethylene (ePTFE)-based local
      infusion device that delivers therapeutic agents directly through the graft wall
      in the region adjacent to the upstream anastomosis, thereby achieving a high drug
      concentration downstream along the graft-blood interface. In this study we
      evaluated the effects of infusing heparin by this method on graft patency and
      neointimal hyperplasia in a canine model of femoral vein replacement. Five dogs
      underwent bilateral femoral vein replacement with the device. In each case one
      graft was infused with continuous heparin (48 U/kg/day) while the contralateral
      control graft received phosphate-buffered saline solution for 14 days. All
      heparin-treated grafts were patent and all control grafts were thrombosed at 14
      days. There was no significant difference in systemic activated partial
      thromboplastin time among samples taken preoperatively, at 48 hours, and at 14
      days of implantation (p > 0.5). There was no significant difference in neointimal
      hyperplasia between the upstream and downstream anastomoses in heparin-treated
      grafts. These data demonstrate that the transgraft infusion of heparin preserved
      venous ePTFE graft patency without measurable systemic anticoagulation. Thus this
      approach may represent an attractive strategy for maintaining patency of
      synthetic venous grafts.

PMID- 8733868
TI  - Totally laparoscopic aortobifemoral bypass grafting in an experimental model:
      description of technique with initial surgical results.
AB  - Our aim was to examine the feasibility of a totally laparoscopic insertion of a
      bifurcated aortofemoral bypass graft in a canine model and to compare the
      surgical results with those in control animals undergoing standard grafting and
      laparoscopic-assisted bypass procedures. Using a six-port approach, we exposed
      and cross clamped the aorta, tunneled a bifurcated Dacron graft, and performed an
      end-to-end aortic anastomosis while maintaining pneumoperitoneum by means of CO2.
      Proximal anastomoses were performed with 4/0 double-ended continuous Prolene
      sutures and distal anastomoses were performed through standard groin incisions.
      Total operating and aortic cross-clamp times were measured as was the total blood
      loss for each procedure. Clinical outcome was also documented. Eight female
      laboratory-bred hounds underwent successful totally laparoscopic aortobifemoral
      bypass grafting, eight underwent "open" grafting, and eight underwent
      laparoscopic-assisted bypass. Mean operating time was 193 minutes in the animals
      undergoing totally laparoscopic insertion vs. 156 minutes in the open group and
      180 minutes in the laparoscopic-assisted group. Aortic cross-clamping time was
      also significantly longer at 87 minutes vs. 43 minutes (p < 0.001) in the totally
      laparoscopic group, but blood loss was less. All eight laparotomy and
      laparoscopic-assisted dogs were still alive with no complications at 28 days,
      whereas three of the eight in the totally laparoscopic group showed evidence of
      temporary paraplegia. This experimental study demonstrates that a totally
      laparoscopic approach can be used to insert a bifurcated aortofemoral bypass with
      a proximal end-to-end anastomosis but currently does not save time and may
      increase the risk of neurologic complications.

PMID- 8733869
TI  - Reduction of aneurysm pressure and wall stress after endovascular repair of
      abdominal aortic aneurysm in a canine model.
AB  - A canine model was designed to evaluate the changes in abdominal aortic aneurysm
      (AAA) pressure and wall stress after endovascular repair. Eight canines underwent
      laparotomy and creation of an AAA. The aneurysm was then excluded with a
      transluminally placed endovascular graft (TPEG) inserted through the right
      femoral artery and deployed across the AAA to exclude the infrarenal aortic
      branches from aortic perfusion. Blood pressure and flow data were recorded for 6
      hours. The AAA blood pressure decreased from 135 +/- 9.3 mm Hg before exclusion
      to 45 +/- 17.6 mm Hg at 10 minutes after exclusion (p < 0.001). At 6 hours, AAA
      blood pressure had declined further to 26 +/- 12.5 mm Hg. Blood flow in the
      excluded iliac artery decreased from a baseline of 242 +/- 58 ml/min to 41 +/- 29
      ml/min 10 minutes after TPEG placement (p < 0.001). At 6 hours, flow was reduced
      to 12 +/- 3.5 ml/min (p < 0.05 compared with that at 10 minutes). Aortic wall
      stress was significantly reduced by TPEG placement but was only slightly lower
      than baseline aortic wall stress before AAA creation. The lumbar arteries were
      patent with retrograde flow in all cases and were found to be the major
      contributors to postexclusion aneurysm pressure. Endovascular AAA exclusion
      results in an immediate decrease in blood pressure and wall stress within the
      excluded aneurysm, but the aneurysm remains perfused by retrograde flow through
      the lumbar arteries, which resulted in near-baseline levels of aneurysm wall
      stress in this canine model. Embolization of patient lumbar vessels at prosthesis
      placement may further reduce the risk of late rupture.

PMID- 8733871
TI  - Femoropopliteal bypass for claudication: vein vs. PTFE.
AB  - The vascular graft of choice for femoropopliteal bypass in patients with
      intolerable claudication is controversial. We retrospectively reviewed our
      experience with 239 patients suffering from claudication secondary to superficial
      femoral artery obstruction. Femoropopliteal reconstruction was performed with
      saphenous vein to the below-knee popliteal artery in 66 patients (BK-vein).
      Polytetrafluoroethylene (PTFE) was used in 128 patients as a bypass graft to the
      above-knee popliteal artery (AK-PTFE) and 45 patients had a PTFE graft to the
      below-knee popliteal artery (BK-PTFE). All patients were enrolled in a
      postoperative graft surveillance program with graft revision when appropriate.
      There was one perioperative death (0.4%). Primary patency at 5 years for AK-PTFE,
      BK-PTFE, and BK-vein was 58.0%, and 60.3%, respectively, and was not
      significantly different among the graft groups. Graft revision for failed/failing
      grafts resulted in 5-year secondary patency rates of 79.2% (AK-PTFE), 73.3% (BK
      PTFE), and 74.4% (BK-vein). These secondary patency rates were not statistically
      different. Eventual conversion to a vein graft in patients initially treated with
      PTFE maximized patency in the femoropopliteal segment with 5-year patency rates
      of 84.6% and 93.0% for the AK-PTFE and BK-PTFE graft groups, respectively. Major
      leg amputation was necessary during the entire course of the study in eight
      (3.3%) patients. We conclude that long-term patency rates for femoropopliteal
      bypass in patients with intolerable claudication are similar for PTFE and
      autologous saphenous vein grafts.

PMID- 8733870
TI  - Resistance to activated protein C: a common inherited cause of venous thrombosis.
AB  - Resistance to activated protein C (RAPC) is a newly recognized hypercoagulable
      state that was first described in 1993. It has become apparent that RAPC is even
      more common than deficiencies in protein C, protein S, or antithrombin III (AT
      III) and affects an estimated 5% of the general population. The majority of
      patients with RAPC have an abnormality in factor V (Arg506Gln), which renders
      factor Va resistant to degradation by activated protein C. Studies in 75 patients
      referred to the Hematology Laboratory at Walter Reed Army Institute of Research
      (WRAIR) over a 14-month period for evaluation of venous thromboembolism were
      reviewed to determine the percentage of those with RAPC. Of the 75 patients in
      the study, one was deficient in protein S, one was deficient in protein C, and
      none was deficient in AT-III. In contrast, 27 (36%) patients tested positive for
      RAPC. Blood was available for DNA analysis in 15 patients with RAPC. Of these 15
      patients, nine (60%) tested positive for the Arg506Gln mutation in factor V. Six
      other patients with RAPC did not have the factor V mutation. Additional risk
      factors for thrombosis were immobility, obesity, use of oral contraceptives, and
      pregnancy. The majority of patients had deep venous thrombosis of the lower
      extremities; 71% had a recurrence if not placed on chronic anticoagulation
      therapy. Thus RAPC is a significant risk factor for venous thrombosis. Evaluation
      for inherited hypercoagulable states should include testing for this newly
      described condition.

PMID- 8733872
TI  - Correction of lower extremity deep venous incompetence by ablation of superficial
      venous reflux.
AB  - Chronic venous insufficiency which produces lipodermatosclerosis, varicosities,
      or ulceration, is frequently caused by superficial venous reflux and deep venous
      incompetence. The anatomy of venous insufficiency has been clarified with duplex
      ultrasound, thus allowing appropriately directed therapy. However, postoperative
      venous physiology in patients undergoing superficial venous ablation has been
      infrequently reported. This study was undertaken to document the effect of
      superficial venous ablation on deep venous reflux. Between April 1994 and May
      1995, 45 patients were examined preoperatively with duplex ultrasound. All
      patients had symptomatic venous insufficiency and were found to have greater
      saphenous vein reflux. Clinical classification of venous insufficiency (according
      to the criteria of the joint councils of the vascular societies) included class I
      in 30 patients, class II in 12, and class III in 3. Seventeen patients (38%) had
      reflux in the femoral venous system in addition to superficial reflux. All
      patients underwent removal of the proximal greater saphenous vein in concert with
      multiple stab avulsions of identified varicosities. Postoperative interrogation
      of the venous system revealed that in 16 (94%) of 17 patients, coexistent femoral
      venous insufficiency completely resolved. Thus ablation of superficial venous
      reflux eliminated incompetence in the deep venous system in patients with
      combined disease. These preliminary results suggest that superficial venous
      incompetence may be a cause of deep venous insufficiency. Whereas alternative
      methods to correct deep venous insufficiency have met with limited success, it
      appears that saphenectomy (when combined disease is present) may be effective in
      correction of deep venous reflux.

PMID- 8733873
TI  - Technique of reversed vein bypass for lower extremity ischemia.

PMID- 8733874
TI  - Moderate hypothyroidism in preparation for whole body 131I scintiscans and
      thyroglobulin testing.
AB  - Patients who have undergone thyroidectomy for thyroid carcinoma are frequently
      subjected to periods of induced severe hypothyroidism in preparation for 131I
      whole body scanning and measurement of serum TG. These two tests are crucial in
      evaluating the patient's clinical status and determining administration of 131I
      or other necessary treatment. Severe hypothyroidism produces fatigue, weight
      gain, depression, inability to carry out usual activities, and occasionally
      significant illness. We compared the efficacy of inducing moderate hypothyroidism
      by cutting replacement therapy in half, to a standard method. In the standard
      preparation, patients substituted triiodothyronine for thyroxine replacement over
      a 3-week period, and then omitted hormone therapy for 3 weeks. For the subsequent
      scan, 6 to 12 months later, the thyroxine dosage was cut in half. TSH levels were
      assessed 4 weeks later, and if adequately elevated, whole body scanning was
      conducted at the end of the fifth week. Pulse, weight, clinical symptoms, thyroid
      hormone levels, and some clinical chemistries were evaluated prior to each scan,
      and some of the tests were also carried out during the interval between scans.
      Moderate hypothyroidism induced by the half-dose protocol induced TSH elevations
      above the target level (25-30 microU/mL) at 5 weeks in most patients. Typically
      TSH of 15 microU/mL in the previous week predicted adequate elevation of TSH at
      the time of scan. Half dose therapy can be prolonged, if necessary, especially in
      patients who begin with extreme suppression of TSH, or if a higher TSH is
      desired. Pulse, weight gain, and cholesterol were significantly different in the
      two protocols, and the patient's subjective evaluation of hypothyroid symptoms
      was significantly reduced. Reduction of thyroxine replacement dosage to half the
      usual amount, in patients with thyroid cancer, allows after 5 weeks in most
      patients sufficient elevation of TSH for whole body scanning and measurement of
      TG levels. This simple and economical procedure drastically reduces
      symptomatology of hypothyroidism and makes this key procedure much more tolerable
      to patients.

PMID- 8733875
TI  - Fine adjustments in thyroxine replacement and its effect on bone metabolism.
AB  - We studied 10 postmenopausal women with Hashimoto's hypothyroidism treated with
      varying doses of L-thyroxine replacement. Each patient received incremental doses
      of L-thyroxine sufficient to achieve subclinical hypothyroidism, euthyroidism,
      and subclinical hyperthyroidism as determined by normal total serum thyroxine
      levels (80-160 micrograms/L) and serum TSH concentrations greater than 3.5, 0.3
      3.5, and less than 0.3 mU/L, respectively. Metabolic parameters of bone turnover
      (including serum bone Gla-protein, serum alkaline phosphatase, serum procollagen
      1, and serum carboxytelopeptide) were assessed once steady state was achieved,
      and measurements were compared to 10 healthy controls matched for age and years
      since the menopause. Our findings suggest that overzealous thyroxine replacement
      producing subclinical hyperthyroidism may result in an increase in bone turnover
      as reflected by elevated serum carboxytelopeptide concentrations.

PMID- 8733876
TI  - Extremely low doses of heparin release lipase activity into the plasma and can
      thereby cause artifactual elevations in the serum-free thyroxine concentration as
      measured by equilibrium dialysis.
AB  - Heparin can cause an artifactual elevation in the concentration of unbound (free)
      thyroxine (T4) in the plasma, particularly when measured by equilibrium dialysis.
      The lipase released into the plasma by heparin acts on substrate (triglycerides;
      TG) in the plasma in vitro to release nonesterified (free) fatty acids (FFA),
      which, in high concentrations, inhibit the binding of T4 to its plasma binding
      proteins. This artifact occurs only in the presence of sufficient substrate
      (serum TG greater than approximately 180 mg/dL), and is most pronounced in
      methods requiring long incubation times. We observed this artifact in a patient
      receiving intralipid and subcutaneous (sc) heparin. Plasma-free T4, when measured
      by equilibrium dialysis, was elevated, but was normalized when the in vitro
      generation of FFA during equilibrium dialysis was prevented by prior treatment of
      the sample with protamine to inhibit lipoprotein lipase and with an antibody to
      hepatic triglyceride lipase. This observation caused us to investigate formally
      whether heparin, at standard sc doses or at iv doses even lower than those that
      are commonly used to flush iv lines (100-300 U), could also cause this artifact.
      We gave increasing doses of heparin at weekly intervals to each of three normal
      volunteers and measured FFA generation in their plasma (supplemented with 250
      mg/dL triglycerides) under conditions simulating equilibrium dialysis. We found
      that, indeed, iv doses of heparin as low as 0.08 U/kg (5.6 U in a 70-kg subject)
      as well as a standard dose of sc heparin (5000 U) could release significant
      lipase activity into the plasma and, in the setting of sufficient substrate,
      cause enough in vitro generation of FFA to artifactually increase the serum-free
      T4 concentration when measured by equilibrium dialysis. These results indicate
      that equilibrium dialysis may not always be the best method for assessing serum
      free T4 concentrations in hospitalized patients, and should be taken into account
      when interpreting previous studies demonstrating inhibitors of T4-serum protein
      binding in sera from hospitalized patients.

PMID- 8733877
TI  - Effects of metoclopramide on fasting-induced TSH suppression.
AB  - Short-term caloric deprivation leads to suppression of TSH secretion in healthy
      subjects, but the mechanism of this effect is unknown. Since dopamine inhibits
      TSH secretion at physiologic levels, increased endogenous dopamine activity may
      cause the TSH suppression observed during fasting. To test this hypothesis, 11
      healthy subjects underwent four studies: (1) Baseline-subjects were allowed ad
      libitum food. (2) MCP-subjects were allowed ad libitum food and received iv
      metoclopramide (MCP) at 30 micrograms/kg/h over 48 h. (3) Fasting-subjects
      received no caloric intake for 56 h. (4) Fasting+MCP-subjects fasted for 56 h,
      and received iv MCP during the final 48 h of the study. Serum TSH levels were
      measured every 15 min during the final 24 h of each study, and a TRH stimulation
      test was performed at the conclusion of each study: 56 h of fasting decreased 24
      h mean TSH levels and TSH pulse amplitude by 40%, with blunting of the TSH
      response to TRH. MCP infusions increased 24 h mean TSH levels and TSH pulse
      amplitude 26-34%, with no differences between the fasting and nonfasting studies.
      MCP infusions did not normalize TSH levels, TSH responses to TRH, or serum T3
      levels during fasting. These data suggest that endogenous dopaminergic activity
      does not play a major role in fasting-induced TSH suppression in healthy
      subjects.

PMID- 8733878
TI  - Increased urinary excretion of sulfated 3,3',5-triiodothyronine in patients with
      nodular goiters receiving suppressive thyroxine therapy.
AB  - Increased serum 3,3',5-triiodothyronine sulfate (T3S) levels have been detected
      in various pathophysiologic states. However, little is known about T3S
      concentrations in other biological fluids. By employing a highly sensitive,
      specific, and reproducible radioimmunoassay (RIA), we measured T3S in the serum
      and urine of 20 premenopausal women with benign nodular goiters before and after
      administration of thyroxine for 6 months (T4; 3.2 micrograms/kg/day). Serum T3
      concentrations did not change significantly after treatment (2.0 vs. 1.7 nmol/L;
      p > 0.05). However, the mean serum T4 and free T4 concentrations were
      significantly higher after treatment (138 vs. 88 nmol/L and 28 vs. 17 pmol/L; p <
      0.01, respectively). Serum thyroid stimulating hormone (TSH) levels were
      significantly reduced after T4 treatment (0.13 vs. 0.66 mU/L, p < 0.01) and the
      serum levels of T3S were significantly increased after treatment (82 vs. 45
      pmol/L; p < 0.01). A good correlation was observed between increased serum T3S
      and T4 concentrations (r = 0.66; p < 0.001). The sulfoconjugate of T3 was
      significantly increased in creatinine-corrected urine after treatment (606 vs.
      253 pmol/umol Cr.; p < 0.01). There was a significant correlation between
      increased creatinine-corrected urine T3S and increased serum free T4 (r = 0.65; p
      < 0.001). In summary, significant increases in serum and urine T3S levels were
      noted in T4-treated patients with subnormal serum TSH and borderline elevated T4.
      We thus conclude that the sulfation pathway may play a role in the homeostasis of
      thyroid hormone metabolism in T4-treated subjects with relative
      hyperthyroxinemia. In addition, the creatinine-corrected urine concentrations of
      T3S may serve as an index for the evaluation of T4-treated patients with elevated
      levels of T4.

PMID- 8733879
TI  - Different cytokine mRNA profiles in Graves' disease, Hashimoto's thyroiditis, and
      nonautoimmune thyroid disorders determined by quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR).
AB  - Intrathyroidal lymphocytes are a source of cytokines thought to stimulate or
      maintain the immune process within the thyroid in Graves' disease (GD) and
      Hashimoto's thyroiditis (HT). Quantitative assessment of the cytokine profile may
      provide important clues as to the Th1/Th2 balance prevailing in these diseases.
      We analyzed cytokine mRNA expression levels in thyroid tissue samples from 13
      patients with GD, 2 with HT, 5 with nontoxic multinodular goiter (NTG), and 4
      with thyroid autonomy (nodular = TAnod and perinodular = TAperi tissue) using
      multispecific competitor fragments with primer sequences for IL-1 beta, IL-2, IL
      4, IL-6, IL-8, IL-10, IFN-gamma, CD25, and CD3 delta-chain mRNA. Patients with GD
      were subdivided into two groups according to their serum levels of antibodies to
      thyroperoxidase (anti-TPO; GDhigh > 4000 U/mL, GDlow < or = 200 U/mL). These
      levels correlated positively with the CD3 delta-chain mRNA levels (r = 0.83) and
      with the T cell infiltration (r = 0.71) as determined by immunohistochemistry.
      Patients with GDhigh demonstrated 2- to 4-fold higher IL-4 mRNA levels (as
      compared to all other investigated groups) and significantly higher IL-10 mRNA
      levels as compared to HT, GDlow, and TAnod patients. Patients with GDhigh also
      had significantly higher levels of IFN-gamma, IL-1 beta, IL-8, and CD25 mRNA as
      compared to GDlow. The highest IFN-gamma, IL-2, and CD25 mRNA levels were found
      in HT. The lowest mRNA levels of all the investigated groups were detected in
      TAnod. No significant differences in IL-6 and IL-8 mRNA levels were found between
      most of the patient groups. In summary, patients with GDhigh showed a shift to a
      more Th2-driven cytokine pattern. In contrast, the increase mRNA levels of Th1
      related cytokines found in HT indicate predominantly T cell-mediated cytotoxic
      processes.

PMID- 8733880
TI  - A prospective study of the effect of nonionic contrast media on thyroid function.
AB  - To observe the effect of iodine in nonionic contrast media on thyroid function,
      we measured free thyroxine (FT4) and thyroid stimulating hormone (TSH) following
      nonionic contrast radiography in 73 patients (49 males; 24 females) aged 50 to 84
      years, mean 65.7 years. FT4 was significantly (p < 0.01) raised above baseline at
      8 weeks but not 4 weeks following contrast injection (mean +/- standard
      deviation, 17.1 +/- 5.9 and 14.3 +/- 4.0 vs 13.3 +/- 2.7 pmol/L at baseline);
      however, TSH was significantly (p < 0.03) depressed at both 4 and 8 weeks (1.09
      +/- 0.68 and 1.21 +/- 1.56 vs 1.40 +/- 0.90 mIU/L). T3 did not change
      significantly. FT4 rose by more than 20% in 15/73 and TSH fell by more than 20%
      in 41/73 compared to a fall of FT4 in 3/73 and a rise in TSH of 8/73 (p < 0.005
      and < 0.001, respectively). Two patients became hyperthyroid and in four others
      either FT4 was elevated or TSH suppressed, one of whom developed atrial
      fibrillation. Although frank hyperthyroidism following contrast radiography was
      uncommon, there was a significant trend towards thyroid stimulation rather than
      suppression after iodine exposure. This may be related to the age of the patients
      studied.

PMID- 8733881
TI  - Thyroid dysfunction in ambulatory elderly Chinese subjects in an area of
      borderline iodine intake.
AB  - Thyroid dysfunction has been reported to occur in 10% of the elderly population
      in Caucasians. As the nature and prevalence vary tremendously between ethnic
      groups, and no data are available for Chinese, a primary thyrotropin (TSH)
      screening program using a supersensitive TSH assay was performed on 1880
      ambulatory elderly southern Chinese aged above 60 in Hong Kong, an area of
      borderline iodine intake. Full thyroid function testing was performed on 600
      randomly selected samples with normal TSH values and also on subjects with
      abnormal TSH levels. The results showed that TSH decreased with age in women (p <
      0.05) but not in men. The median values for TSH for women 60-69, 70-79, and > 80
      years old were 1.40, 1.30, and 1.20, respectively, while for men it was 1.30
      mIU/L. Elevated TSH values (> 5.0 mIU/L) were found in 19 (1.0%) while suppressed
      TSH values (< 0.1 mIU/L) were present in 28 (1.5%) subjects. Biochemical
      hypothyroidism and hyperthyroidism were present in 3 and 12 subjects,
      respectively. Two-thirds of the subjects with abnormal TSH values had antithyroid
      antibodies. Full assessment of the 600 subjects revealed the prevalence rates for
      antithyroglobulin and antithyroid peroxidase antibody of 10.2 and 11.2%,
      respectively. Those who were positive for antithyroid antibodies had
      significantly higher TSH levels (p < 0.005). Free T4 decreased (p < 0.01) while
      free T3 increased (p < 0.001) with age in the females resulting in higher free
      T3/free T4 ratio with aging (p < 0.001). This, however, was not seen in the
      males. In conclusion, thyroid dysfunction in elderly Chinese occurs predominantly
      in the female. The cause could be explained by both autoimmune thyroid disease as
      well as iodine insufficiency.

PMID- 8733882
TI  - RET mutation screening in MEN2 patients and discovery of a novel mutation in a
      sporadic medullary thyroid carcinoma.
AB  - RET germline mutations were found to predispose to the development of three
      variants of multiple endocrine neoplasia type 2, MEN2A, MEN2B, and familial
      medullary thyroid carcinoma (FMTC). We have screened for RET mutations at exons
      10, 11, 13, and 16 in leukocyte DNA extracted from 37 individuals, and have
      identified RET germline mutations in 12 affected individuals from 9 unrelated
      families. No RET germline mutation was found in 19 individuals with apparent
      sporadic diseases. We have also screened for RET mutations at exons 10, 11, and
      16 in tumor DNA extracted from 13 freshly frozen medullary thyroid carcinomas
      (MTC). RET mutation was detected in every tumor, either inherited or sporadic,
      indicating that RET plays an important role in the development of both inherited
      and sporadic MTC. We initially screened for RET mutations by direct DNA
      sequencing of the genomic PCR products amplified from patients' leukocyte or
      tumor DNA. Recently, we utilized the "Cold SSCP" method, nonradioactive single
      stranded conformation polymorphism analysis, to screen for RET mutations and have
      identified a novel mutation, a 6-bp deletion preceding the cysteine-634, in a
      sporadic MTC.

PMID- 8733883
TI  - Differential induction of fos and jun family genes by thyrotropin in rat thyroid
      FRTL-5 cells.
AB  - Effect of thyrotropin (TSH) on the expression of the members of fos and jun
      family genes in a rat thyroid cell line (FRTL-5) was examined by the reverse
      transcription-polymerase chain reaction (RT-PCR) method. FRTL-5 cells were
      maintained in a TSH-deprived medium for 5 days. After 1 mU/mL TSH addition, the
      cells were harvested at intervals. Total RNA extracted from the cells was
      subjected to RT-PCR. TSH induced a rapid and transient expression of c-fos, fosB,
      and fra-1 with different kinetics. Increase in c-fos mRNA was most rapid with a
      peak level at 30 min after TSH addition. The fosB mRNA reached a peak level at 60
      min poststimulation with a rapid decline at 90 min. The fra-1 mRNA increased at
      60 min followed by a gradual decrease until 120 min. The change in fra-2 mRNA
      level was similar to that of fra-1. TSH induced similar changes in the levels of
      c-jun and junB mRNAs. They significantly increased within 30 min followed by a
      sustained high level until 90 min. The differential induction of fos and jun
      family genes suggests an important role of their gene products on the regulation
      of thyroid cell function by TSH.

PMID- 8733884
TI  - Preliminary determination of a molecular basis of chronic fatigue syndrome.
AB  - Chronic fatigue syndrome (CFS/ME) is a debilitating fatigue illness that has an
      unknown etiology. We studied 20 chronic fatigue syndrome (CFS) patients, who
      complied with the Oxford and American CDC definitions, and 45 non-CFS subjects.
      Participants completed questionnaires, were clinically examined, and had first
      morning urine specimens collected, which were screened by gas chromatography-mass
      spectrometry for changes in metabolite excretion. Multivariate analysis of the
      urinary metabolite profiles differed significantly in the CFS patients compared
      to the non-CFS patients (P < 0.004). The CFS patients had increases in
      aminohydroxy-N-methylpyrrolidine (P < 0.00003, referred to as chronic fatigue
      symptom urinary marker 1, or CFSUM1), tyrosine (P < 0.02), beta-alanine (P <
      0.02), aconitic acid (P < 0.05), and succinic acid (P < 0.05) and reductions in
      an unidentified urinary metabolite, CFSUM2 (P < 0.0007), alanine (P < 0.005), and
      glutamic acid (P < 0.02). CFSUM1, beta-alanine, and CFSUM2 were found by
      discriminant function analysis to be the first, second, and third most important
      metabolites, respectively for discriminating between CFS and non-CFS subjects.
      The abundances of CFSUM1 and beta-alanine were positively correlated with symptom
      incidence (P < 0.01 and P < 0.001, respectively), symptom severity, core CFS
      symptoms, and SCL-90-R somatization (P < 0.00001), suggesting a molecular basis
      for CFS.

PMID- 8733885
TI  - The role of calcium in the artificially induced decidual cell reaction in
      pseudopregnant mice.
AB  - The present study was designed to test the hypothesis that Ca2+ is required for
      the successful induction of the decidual cell reaction (DCR) in mice following
      stimulation with concanavalin A (Con A). Con A (125 micrograms) administered
      intraluminally on Day 4 of pseudopregnancy increased uterine vascular
      permeability increased uterine weight, and induced morphological and histological
      transformations that were clearly indicative of decidualization. Radioactive
      CaCl2 (1 mmol liter-1, 600 mCi mmol-1 introduced into the uterine lumen with
      either Con A or saline was subsequently incorporated into the uterine tissue and
      detected only in the luminal epithelium by microautoradiography techniques. The
      intraluminal administration of CaCl2 in combination with Con A increased the
      magnitude of the lectin-induced DCR. In contrast, the administration of other
      cationic chloride solutions, at various concentrations and tonicity, either had
      no effect (viz. Na+, Mg2+, and Ba2+) or reduced (viz. K+, Zn2+, Cd2+, and La3+)
      this uterine response. While ionophore A23187 was also deciduogenic, it
      suppressed the DCR when administered before Con A and enhanced the DCR when
      administered after Con A. The Ca2+ channel blockers, nifedipine, verapamil,
      nicardipine, and diltiazem, the Ca(2+)-calmodulin inhibitor, W7, and the Ca(+)
      ATPase inhibitor, thapsigargin also effectively reduced the uterine response to
      Con A when administered intraluminally. However, the Con A A-induced DCR was not
      influenced by the Ca+ chelators, EGTA, EDTA, BAPTA, and BAPTA-AM. The results
      confirm that Con A is deciduogenic in pseudopregnant mice and suggest that
      luminal Ca2+ plays an important role in facilitating the induction of the lectin
      induced DCR by influencing the metabolism of the luminal epithelium.

PMID- 8733886
TI  - Effects of insulin, epinephrine, and glucose on regulation of transcription of
      the serine dehydratase gene in newborn dogs.
AB  - Our previous investigation showed that hyperinsulinemia incompletely suppressed
      the transcription of the gene encoding L-serine dehydratase (SDH) (EC 4.2.1.13),
      a gluconeogenic enzyme, in newborn dogs. To test another hypothesis that insulin
      resistance in newborn mammals may be partially due to counterregulatory factors,
      such as epinephrine, euglycemic hyperinsulinemic clamps, hyperglycemic
      hyperinsulinemic clamps, and hyperglycemic hyperinsulinemic hyperepinephrinemic
      clamps were performed in newborn dogs in the present study. The infusion rates of
      insulin and epinephrine were 30 m U/kg/min and 150 ng/kg/min, respectively; the
      glucose infusion rate was adjustable. The SDH mRNA levels in kidney and liver of
      newborn dogs were quantitatively analyzed by using rat SDH cDNA probe and by a
      personal densitometer. The results showed that insulins, glucose, and epinephrine
      did not change the kidney SDH mRNA level; hyperinsulinemia and hyperglycemia
      reduced the liver SDH mRNA level by 8.5 and 29.2%, respectively; in the presence
      of hyperglycemia and hyperinsulinemia, epinephrine was able to increase the liver
      SDH mRNA by 27.8%, almost offsetting the reduction of the liver SDH mRNA level
      induced by the combination of insulin and glucose. We conclude that the enhanced
      regulatory effect of epinephrine counteracting insulin on SDH gene transcription
      in liver of newborn dogs may be one of the mechanisms responsible for the
      neonatal insulin resistance which contributes to neonatal hyperglycemia.

PMID- 8733887
TI  - D-glucose metabolism in BRIN-BD11 islet cells.
AB  - A novel insulin-secreting cell line, BRIN-BD11, was recently established
      following electrofusion of RINm5F cells with NEDH rat pancreatic islet cells. In
      the present study, D-glucose metabolism was compared in BRIN-BD11 and RINm5F
      cells. The concentration dependency of D[5-3H]glucose utilization displayed a
      comparable pattern in the two cell lines, but the absolute values were lower in
      BRIN-BD11 than RINm5F cells. Except in the case of D-[1-14C]glucose, the ratio
      between 14C labeled D-glucose oxidation and D-[5-3H]glucose utilization was
      higher, however, in BRIN-BD11 than RINm5F cells. Moreover, BRIN-BD11 cells were
      less affected than RINm5F cells by a rise in D-glucose concentration, in terms of
      the inhibitory action of the hexose upon oxidative variables, such as oxidative
      glycolysis, pyruvate decarboxylation, and oxidation of glucose-derived acetyl
      residues in the Krebs cycle. The total energy yield from D-glucose catabolism
      appeared similar, however, in BRIN-BD11 and RINm5F cells. These findings extend
      the knowledge that BRIN-BD11 cells display an improved metabolic and secretory
      behavior, when considering the difference otherwise found between normal and
      tumoral islet cells.

PMID- 8733888
TI  - Effects of short-chain acyl-CoA dehydrogenase deficiency on development
      expression of metabolic enzyme genes in the mouse.
AB  - Patients with an acyl-CoA dehydrogenase deficiency share the disease features of
      hypoglycemia, hyperammonemia, tissue fatty change, hypoketonemia, carnitine
      deficiency, and organic acidemia due to apparent disruption of normal fatty acid,
      glucose, and urea metabolism. Most of the acute clinical episodes occur in young
      children. These episodes are precipitated by fasting and are often fatal, with
      the in vivo mechanisms essentially unknown. Since the genes of the rate
      controlling enzymes of these pathways are tissue and developmentally regulated at
      the transcriptional level, we measured, throughout neonatal development, the
      steady-state mRNA levels of long-chain, medium-chain, and short-chain (SCAD) acyl
      CoA dehydrogenases, pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase
      (PEPCK), carbamyl phosphate synthetase I (CPS), ornithine transcarbamylase (OTC),
      and argininosuccinate synthetase (AS) in fed or fasted SCAD-deficient BALB/ByJ
      mice compared to BALB/cBy controls. Overall, our results showed no major effects
      on expression of acyl-CoA dehydrogenases due to SCAD deficiency, regardless of
      age or fasting. In SCAD-deficient mice we found depressed mRNA expression and
      enzyme activity for the urea cycle enzymes CPS and AS at 6 days of age, and found
      no apparent effects on expression of gluconeogenic enzymes PC or PEPCK. There was
      a period of overall lower gene expression for most genes at 6 and 15 days, which
      appears to be in parallel with the developmental period when children with these
      diseases are most severely affected.

PMID- 8733889
TI  - Guidelines for the retention, storage, and use of residual dried blood spot
      samples after newborn screening analysis: statement of the Council of Regional
      Networks for Genetic Services.
AB  - These guidelines provide scientific information for policy development by state
      health departments considering appropriate use of newborn screening specimens
      after screening tests are finished. Information was collected, debated, and
      formulated into a policy statement by the Newborn Screening Committee of the
      Council of Regional Networks for Genetic Services (CORN), a federally funded
      national consortium of representatives from 10 regional genetics networks.
      Newborn screening programs vary widely in approaches and policies concerning
      residual dried blood spot samples (DBS) collected for newborn screening.
      Recognition of the epidemiological utility of DBS samples for HIV seroprevalence
      surveys and a growing interest in DBSs for DNA analysis has intensified
      consideration of issues regarding retention, storage, and use of residual DBS
      samples. Potentially these samples provide a genetic material "bank" for all
      newborns nationwide. Their values as a resource for other uses has already been
      recognized by scientists, administrators, and judicial officials. Programs should
      promulgate rules for retention and use of residual newborn screening DBS samples
      based on scientifically valid information. Banking of newborn samples as sources
      of genetic material should be considered in light of potential benefit or harm to
      society.

PMID- 8733890
TI  - Effect of erucic acid on platelets in patients with adrenoleukodystrophy.
AB  - In a clinical trial for the management of adrenoleukodystrophy, we analyzed the
      effect of erucic acid (a component of Lorenzo's oil) on platelet number, fatty
      acid composition, and function. Analysis of variance was performed to compare
      platelet counts before starting treatment with Lorenzo's oil and at 6 and 12
      months. We measured platelet fatty acid composition in subjects and control
      patients and correlated these values with their platelet counts using
      discriminant analysis. After 6 months, the mean platelet count decreased from
      247,000/mm3 to 169,000/mm3 (+/- 1 standard deviation 58,000,n =39), P < 0.0001
      compared to 18 subjects on a control diet having a mean baseline platelet count
      of 259,000/mm3 (+/- 1 standard deviation 67,000, n = 19) and at 6 months
      267,000/mm3 (+/- 1 standard deviation 71,000). We found at P < 0.05 that the
      platelet counts showed a strong inverse relationship with erucic acid levels and
      other omega 9 fatty acids that form from the administration of the erucic acid
      component of Lorenzo's oil. Morphologic and platelet sizing measurements suggest
      that the physical properties of platelets may also be affected by erucic acid.
      Our studies show that the ingestion of erucic acid affects platelet biology. This
      indicates that platelet counts and properties are influenced by monounsaturated
      fatty acids, in addition to the well-known effects of polyunsaturated fatty
      acids. In areas of the world where erucic acid is widely ingested, the biology of
      platelets in these populations may be affected.

PMID- 8733891
TI  - Purification of NADH: hypothiocyanite oxidoreductase in Streptococcus sanguis.
AB  - NADH: hypothiocyanite oxidoreductase (NHOR) activity, found in some oral
      Streptococci, is postulated to protect these microorganisms against salivary
      peroxidase-produced hypothiocyanite. NHOR, however, has not been purified so far.
      The purification of NHOR from crude extracts of Streptococcus sanguis NCTC 7863
      strain (by ultrafiltration and anion-exchange chromatography) revealed one
      fraction of 125 +/- kDa. However, SDS-PAGE electrophoresis provided a single
      protein of 21.1 +/- 1.2 kDa. This last discovery suggests that NHOR enzyme is a
      hexameric complex having six subunits.

PMID- 8733892
TI  - The entire genomic sequence and cDNA expression of mouse alpha-galactosidase A.
AB  - The full-length cDNA and genomic sequences encoding mouse alpha-galactosidase A
      (alpha-Gal A; EC 3.2.1.22), a lysosomal galactohydrolase, were isolated and
      characterized. The cDNA's open reading frame encoded 419 amino acids and had 82%
      nucleotide (nt) and 78% amino acid identity with the human sequence, although the
      carboxy terminus of the mouse alpha-Gal A polypeptide was 10 amino acids shorter.
      The functional integrity of the mouse cDNA was demonstrated by transient
      expression in COS-1 cells. Northern analysis revealed two mRNA species of about
      1.6 and 3.4 kb due to alternative polyadenylation signals. The entire 14.4-kb
      mouse genomic sequence was determined; each of its seven exons was interrupted by
      intronic sequence at the identical positions as the exons in the human gene. The
      mouse 5' flanking region (250 nt) had one Sp1, site, five CAAT boxes, and no TATA
      box and had 67% identity with the human promoter region. The gene contained 18
      complete or partial Alu-repetitive elements (13 type 1 and 5 type 2 repeats), and
      three putative functional AATAAA consensus polyadenylation signals were
      identified 72, 1668, and 1682 nt after the TAA termination codon. Use of the 72
      nt site and the 1866 and/or 1682 sites were consistent with the shorter and
      longer transcripts. The availability of the full-length cDNA and genomic sequence
      encoding mouse alpha-Gal A should facilitate structure/function studies of this
      lysosomal glycosidase and the construction of alpha-Gal A-deficient mice by
      targeted gene disruption.

PMID- 8733893
TI  - Genotype D399N/R463C in a patient with type 3 Gaucher disease previously assigned
      genotype N370S/R463C.
AB  - A patient with type 3 Gaucher disease is described with a novel genotype,
      D399N/R463C, established by DNA sequencing. This patient was previously reported
      as having genotype N370S/R463C. This communication now establishes that no
      patients reported with mutation N370S have the neuronopathic forms of Gaucher
      disease and has important implications for genetic counseling.

PMID- 8733894
TI  - Rat macrophages in experimental IgA nephropathy.
AB  - To test whether the peripheral macrophage functions as early index of oxygen free
      radical release in association with the development of IgA nephropathy (IgAN), we
      studied female Lewis rats. IgAN was produced by treatment over 8 weeks with 0.1%
      bovine gamma globulin (BGG) in drinking water, followed by three daily
      intravenous injections of BGG, 1 mg/dose. Fifteen rats were divided randomly into
      three groups: control, IgAN, and IgAN fed vitamin E 100 IU/kg chow. At the end of
      the treatment period, rats were placed in individual metabolic cages for 24-h
      urine collections and then anesthetized with Inactin (100 mg/kg BW) for
      aspiration of peritoneal macrophages. The results (mean +/- SD) extended our
      previous data in male rats, confirming that the elevated proteinuria of IgAN
      (3.62 +/- 0.79 mg/day) was significantly reduced with vitamin E treatment (2.59
      +/- 0.28 mg/day) in female rats (P < 0.002) More importantly, we indicated for
      the first time that oxygen free radicals production by peritoneal macrophages in
      IgAN was significantly reduced by vitamin E: 1.58 +/- 0.91 nmol/10(6) cells/15
      min in the untreated group vs 3.28 +/- 0.54 nmol/10(6) cells/15 min in the
      vitamin E-treated group (P < 0.05).

PMID- 8733895
TI  - Effect of cilostazol on the production of platelet-derived growth factor in
      cultured human vascular endothelial cells.
AB  - Increased levels of platelet-derived growth factor (PDGF) may play a central role
      in the development of arteriosclerosis, but the factors that inhibit PDGF
      production in vascular endothelial cells remain mostly unknown. We examined the
      effects of cilostazol, an antithrombotic agent, and high glucose on PDGF
      production in cultured human umbilical vein endothelial cells (HUVEC). HUVEC
      grown in high glucose exhibits increased PDGF production, which was markedly
      inhibited by cilostazol. Since cilostazol inhibits PDGF production in HUVEC, its
      use may exhibit anti-arteriosclerotic effects in diabetic patients.

PMID- 8733896
TI  - Molecular deletion patterns in Turkish Duchenne and Becker muscular dystrophy
      patients.
AB  - The dystrophin gene deletion patterns of Duchenne/Becker dystrophy were
      investigated in 57 DMD, 7 BMD and 1 DMD-BMD intermediate muscular dystrophy
      patients. Deletions, analyzed by multiplex amplification of selected exons, were
      observed in 58% (38 cases) of the patients. It was found that exon 48 was the
      most frequently affected, while exon 44 was the least frequently affected. The
      number of deleted exons was variable, but single exon deletions were more
      frequent (41%) than larger deletions in our population and the great majority of
      deletions began distal to exon 44. The application of PCR to deletion analysis in
      D/BMD was found to be very useful in delineating the extent of the deletion in
      most of the cases (82%). It was seen that the frequency of deletion breakpoints
      in distal part of the dystrophin gene (exons 42-52) was detected in 64% of our
      cases. In our group, the frequency of deletion breakpoints in the same area of
      the dystrophin gene was between that of the French and the Finnish patients. The
      distribution of deletion breakpoints within the dystrophin gene of the Turkish
      population seems to have some differences from other populations. Deletion
      breakpoints were found to be clustered mainly in three separate regions covering
      introns 44, 45 and 50 within the central region of the dystrophin gene. Intron 44
      was mostly 5' breakpoints but it was found not to be involved as 3' breakpoints.
      The correlation between phenotype and type of deletion agreed with the reading
      frame theory except for one DMD case.

PMID- 8733897
TI  - Cerebellar and subcortical blood flow abnormalities in children with partial
      epilepsy.
AB  - Cerebellar and cerebral subcortical blood flow in 41 children with partial
      epilepsy and 6 normal controls was investigated during the interictal state using
      single photon emission computed tomography with technetium-99m
      hexamethylpropyleneamineoxime. Seventeen of 41 patients had been treated with
      antiepileptic drugs (AEDs) for 4.65 +/- 3.80 years (range 0.2-12) and 24 patients
      were drug-free. Unilateral hypoperfusion of cerebellum and cerebral subcortical
      gray matter was demonstrated in 11 (28%) and 16 (40%) patients, respectively.
      Most of them also had focal cerebral cortical perfusion abnormalities,
      ipsilateral or contralateral to the cerebellar and cerebral subcortical
      hypoperfusion. The mean asymmetry indices of cerebellar blood flow in the
      medicated and the unmedicated patients were significantly higher than in the
      control cases (P < 0.02 and P < 0.04), whereas the differences in the asymmetry
      indices in cerebral subcortical areas were insignificant. AED therapy did not
      affect the perfusion of cerebellum and cerebral subcortical regions (P > 0.05 and
      P > 0.05). Our results suggest that functional alterations on anatomically
      connected remote areas in patients with partial epilepsy are not related to the
      drug effect and probably due to primary epileptogenic activity.

PMID- 8733898
TI  - Brainstem auditory and visual evoked potentials in infants with myelomeningocele.
AB  - Brainstem auditory evoked potentials (BAEPs) and visual evoked potentials (VEPs)
      were recorded in 47 infants with myelomeningocele to determine if the evoked
      potentials reflected the early neurological status, and if they had prognostic
      value as to the children's neurological outcome. The infants were tested between
      1 day and 3 months of age (mean 24 days), while still in hospital after the
      myelomeningocele repair. Outcome was assessed at a mean of 2 years of age. Normal
      BAEPs were found in 41% and normal VEPs in 62% of the patients. BAEPs were
      abnormal in all infants studied who had symptomatic Arnold-Chiari (AC)
      malformation (n = 9); VEPs were abnormal in only 55% of symptomatic infants. Of
      the infants who did not have symptomatic AC malformation, 53% had normal BAEPs,
      69% had normal VEPs. Of the patients with normal BAEPs, 81% had normal cerebral
      function on follow-up. Of the patients with abnormal BAEPs, 87% had central
      neurological abnormalities on follow-up. Of the patients with normal VEPs, 63%
      were normal on follow-up; of the patients with abnormal VEPs, 71% were abnormal
      on follow-up. Thus, the VEPs studied early in the neonatal course do not appear
      to be sufficiently sensitive to be valuable prognostically in these infants.
      However, the BAEPs were consistently abnormal in symptomatic AC malformation and
      showed a positive predictive value of 88% and an accuracy in predicting central
      neurological sequelae of 84%.

PMID- 8733899
TI  - Hematologic manifestations and impaired liver synthetic function during valproate
      monotherapy.
AB  - In a prospective study 50 children with new onset epilepsy were investigated.
      Routine screening for complete blood count, serum protein, albumin, gamma
      glutamyltransferase (gamma-GT), aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), alkaline phosphatase, and coagulation studies before, 3,
      6 and 9 weeks after commencement of antiepileptic therapy with valproate were
      carried out. Serum B12 and folate levels were also determined in 29 patients. The
      aim of the study was to evaluate the effect of VPA on these laboratory findings.
      We found a significant reduction of red blood count and platelet count, whereas
      MCV showed a significant upward trend. Vitamin B12 levels were elevated after
      starting VPA therapy. We found no elevations of liver enzymes, but a significant
      transient reduction of ALT after 3 and 6 weeks and significantly reduced serum
      protein and albumin after 3, 6 and 9 weeks. Coagulation studies revealed a
      significant downward trend in serum fibrinogen and upward trend in thrombin time.
      The other parameters showed no significant changes after onset of VPA treatment.
      We think that reduced red blood cell and platelet counts, and elevated MCV
      indicate a direct toxic effect on a hematopoietic precursor or stem cell in
      patients treated with VPA. Furthermore, reduced protein, albumin and fibrinogen
      indicate an impaired liver synthetic function in asymptomatic children treated
      with VPA monotherapy.

PMID- 8733900
TI  - Vasopressin in the cerebrospinal fluid of febrile children with or without
      seizures.
AB  - Immaturity in water and electrolyte balance in the brain has been considered to
      increase the susceptibility of young animals and children to febrile convulsions
      (FCs). Arginine-vasopressin (AVP) is involved in the regulation of several
      centrally mediated events such as modulation of fever and the ease with which
      water permeates into and out of the brain. To evaluate the possible role of AVP
      in the control of water balance and susceptibility to convulsions during fever we
      measured the AVP concentration in the cerebrospinal fluid (CSF) and plasma of
      febrile children with or without convulsions. The febrile population consisted of
      47 children, of whom 29 experienced seizures during fever. Seven children with
      epileptic symptoms and 18 children without seizures were included as nonfebrile
      controls. The CSF AVP concentration in febrile children without seizures and in
      nonfebrile convulsive children was significantly lower (0.60 +/- 0.07 pmol/l,
      mean +/- SEM, P < 0.01 and 0.65 +/- 0.19 pmol/l, P < 0.05, respectively) than in
      nonfebrile children without convulsions (0.83 +/- 0.06 pmol/l). However, the
      levels of CSF AVP were not significantly different in children with FCs (0.71 +/-
      0.06 pmol/l) compared with other groups. CSF AVP correlated with the CSF
      osmolality (r = 0.33, P = 0.02). No statistical differences in plasma AVP levels
      between the groups could be found. The present data provide support for the
      hypothesis of synchronous regulation of osmolality and AVP concentration in CSF.
      During fever the concentration of CSF AVP was lower in nonconvulsive children
      compared with nonfebrile nonconvulsive children. CSF AVP levels were not affected
      in febrile children by convulsions.

PMID- 8733901
TI  - Pelizaeus-Merzbacher-like disease: female case report.
AB  - We experienced a 15-year-old female, whose healthy parents were second cousins,
      who was suspected of having dysmyelinating disease involving only the central
      nervous system (CNS). She was noticed to have congenital pendula nystagmus, and
      spastic gait disturbance developed at the age of 10 years. Mild athetosis of the
      upper limbs and ataxia were recognized at age 13 years, and dysarthria presented
      at age 15. MRI and electrophysiological findings showed the characteristics of
      Pelizaeus-Merzbacher disease (PMD), although the extensive nerve conduction
      slowing of the CNS was less severe than that in male patients with PMD. No
      promoter or exonic mutations of proteolipid protein (PLP) gene were detected.
      Although this patient might be heterozygous for a mutation of the extraexonic PLP
      gene sequences or of other unknown X-linked PLP associated genes, we speculate
      that this case had a dysmyelinating disease with an autosomal recessive trait
      characterized by the same phenotype as that of PMD.

PMID- 8733902
TI  - Temporary improvement of neurological symptoms with gammaglobulin therapy in a
      boy with adrenoleukodystrophy.
AB  - A 10-year-old boy with adrenoleukodystrophy was treated with gammaglobulin in
      conjunction with a mixture of glyceryl trioleate and glyceryl trierucate. With a
      high dose of gammaglobulin, clinical improvement, including the reduction of
      visual field defects, was noted. On magnetic resonance imaging, attenuation of
      the enhancement of the rim with gadolinium was observed, suggesting repair of the
      blood-brain barrier. When auditory agnosia developed later, a temporary
      improvement was again obtained with gammaglobulin. Although the progress of the
      disease could not be arrested permanently, gammaglobulin therapy seemed to have
      been associated with temporary improvement of the clinical symptoms in this
      patient with adrenoleukodystrophy.

PMID- 8733903
TI  - Prenatal diagnosis of congenital myotonic dystrophy in two Japanese families:
      direct mutation analysis by a non-radioisotope PCR method and haplotype analysis
      with flanking DNA markers.
AB  - The prenatal diagnosis of congenital myotonic dystrophy in two Japanese families
      was reported. The CTG repeat size in the myotonin/protein kinase gene was
      determined by a nonradioisotope PCR method. Polymorphisms of the DNA markers
      (ApoCII, X75b-VSSM and KLK-1) flanking the CTG repeat were analyzed from normal
      Japanese and were used to determine the risk haplotype. Two pregnant women with
      myotonic dystrophy requested prenatal diagnosis. The first case was diagnosed as
      having myotonic dystrophy at 36 weeks of pregnancy. The CTG repeat size in the
      cord blood from the fetus was not expanded and the risk for the disease was
      judged to be low by haplotype analysis with the X75b-VSSM marker. In the second
      case, the chorionic villus was sampled in the pregnant mother who had already had
      two children with congenital myotonic dystrophy. The small expanded allele (36
      repeats) from the mother and a normal allele from the father were detected in the
      chorionic villus. The risk for the disease was not determined by haplotype
      analysis with ApoCII and X75b-VSSM, only being judged as low by haplotype
      analysis with KLK-1 in the second case. These babies from two families were born
      and developed normally. DNA diagnosis for direct CTG repeat expansion combined
      with haplotype analysis has been useful for pregnant women with myotonic
      dystrophy who are at high risk of having severely affected babies.

PMID- 8733904
TI  - CTG trinucleotide repeat length and clinical expression in a family with myotonic
      dystrophy.
AB  - Unstable expansion of the CTG repeats in the 3' untranslated region encoding a
      member of the protein kinase family in the q13.3 band on chromosome 19 is a
      mutation specific for myotonic dystrophy. To examine the correlation between
      clinical expression and CTG trinucleotide repeat length, we carried out Southern
      blot analysis in a family with myotonic dystrophy. In this pedigree, the expanded
      CTG repeats were transmitted maternally. The mother had three female children.
      The mother had about 200 CTG repeats, and the number of repeats for each child
      was about 800, 1500 and 1600 in birth order. The mother and the patient with 800
      repeats were unaware of muscle weakness or myotonia. Symptoms were present from
      age 3 years in the patient with 1500 repeats and from birth in the one with 1600
      repeats. Although the mother menstruated regularly, the patients with 800 and
      1500 repeats both menstruated irregularly, and the one with 1600 repeats has
      never menstruated. The age of onset and severity of the disease were correlated
      with the size of the expanded repeats. Endocrinological studies revealed that the
      basal levels of the gonadotropins, PRL and E2 were within normal range, and a
      pituitary response to LHRH was observed. These data suggest that the amenorrhea
      and menstrual irregularities were caused by a suprahypophyseal dysfunction. When
      expanded CTG repeats are transmitted maternally, abnormal products resulting from
      the metabolic disturbance in the affected mother may harm the fetus in utero. A
      heterozygous fetus, who has more CTG repeats, may be unable to metabolize the
      pathologic products sufficiently and therefore may become more severely affected.
      This may explain the exclusive maternal transmission of congenital myotonic
      dystrophy.

PMID- 8733905
TI  - Merosin-negative non-Fukuyama-type congenital muscular dystrophy: a case report.
AB  - We report a female infant with non-Fukuyama-type congenital muscular dystrophy
      with merosin deficiency. She manifested marked hypotonia and muscle weakness from
      the neonatal period, with an elevated creatine kinase concentration. Her motor
      developmental milestones were markedly delayed; however, her intellectual
      development was normal. Although cranial computed tomography (CT) at 3 months of
      age was normal, subsequent CT at 16 months of age demonstrated diffuse, abnormal
      white matter lucencies. Muscle biopsy findings at 16 months of age were
      compatible with those of congenital muscular dystrophy. In addition, no muscle
      fibers were immunostained by the merosin antibody. The patient died of pneumonia
      at 23 months of age. These clinical symptoms and CT findings are similar to those
      described in patients with merosin-negative congenital muscular dystrophy in
      European countries.

PMID- 8733906
TI  - Severe neonatal nemaline myopathy with delayed maturation of muscle.
AB  - A Japanese infant with a severe neonatal form of nemaline myopathy showed
      features of muscle immaturity as well as rods in the biopsied quadriceps femoris
      muscle, and involvement of diaphragm was first confirmed at autopsy. The biopsied
      muscle showed numerous rods in 80% of muscle fibers, and an increased number of
      type 2C fibers (23.2%). Electron microscopic findings were characterized by the
      presence of many small, immature round fibers with central nuclei and sparse
      myofibrils, and an increased number of satellite cells in close association with
      the small muscle fibers, as well as numerous rod structures. These microscopic
      and electron microscopic findings are interpreted as immature muscle fibers.
      Maturational delay or arrest implies deprivation of a development promoting
      factor such as a neuronal signal. Severe involvement with numerous rods was
      demonstrated in both diaphragm and intercostal muscles at the time of the
      postmortem examination, compatible with the patient's respiratory failure.

PMID- 8733907
TI  - Epilepsy or paroxysmal kinesigenic choreoathetosis?
AB  - Epileptic seizures induced by sudden movement and paroxysmal kinesigenic
      choreoathetosis (PKC) have often been confused in the past, owing to the close
      similarity of the attacks, the equally good response to anticonvulsants, and the
      frequent occurrence of epilepsy and PKC in the same family, or even in the same
      patient. The pathophysiology of PKC is still unclear and its relationship with
      epilepsy open to discussion. The sparing of consciousness and the lack of
      postictal phenomena are constant features of PKC, thus differentiating this
      syndrome from epilepsy. We report the case of an 8-year-old boy with frequent
      brief tonic attacks, without loss of consciousness, triggered by sudden movement.
      The neurologic examination, EEG and MRI did not help to differentiate between
      epilepsy and PKC. Only the occurrence of a longer seizure with clouding of
      consciousness and the recording of the postictal abnormalities on the EEG
      supported a diagnosis of reflex epilepsy induced by movement.

PMID- 8733908
TI  - Proton magnetic resonance spectroscopy on childhood-onset dentatorubral
      pallidoluysian atrophy (DRPLA).
AB  - To evaluate brain dysfunction of childhood-onset dentatorubral-pallidoluysian
      atrophy (DRPLA), three children with progressive myoclonus epilepsy, who were
      diagnosed as having DRPLA by DNA analysis, for the first time, underwent a study
      of proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS obtained from both the
      parietal and basal ganglia regions disclosed markedly reduced ratios of N
      acetylaspartate to both choline and creatine. Especially regarding the basal
      ganglia region, the latter (ratio of N-acetylaspartate to creatine) closely
      correlated to severity of genetic abnormality, i.e. number of expanded CAG
      repeats, suggesting that the degree of neuronal loss in the region strongly
      depends on genetic factors. 1H-MRS must be a valuable tool to clarify the
      pathophysiology of DRPLA.

PMID- 8733909
TI  - Serial MRI findings of benign poliomyelitis.
AB  - A 14-year-old boy presented with incomplete transverse myelopathic symptoms
      associated with mild encephalitis. Magnetic resonance imaging (MRI) revealed
      involvement of the central portion of spinal cord extending from the C1 to T5
      level on T2-weighted images with expansion of the cervical spinal cord. The boy
      made a full clinical recovery in a few weeks. Cultures of the pharyngeal exudate
      were positive for ECHO virus type 11. The lesion on MRI disappeared completely in
      a few months.

PMID- 8733910
TI  - Diffuse white matter lesions associated with herpes simplex encephalitis as
      observed on magnetic resonance imaging.
AB  - A 2-year-old boy with herpes simplex encephalitis developed diffuse brain lesions
      involving the white matter of both cerebral hemispheres. These lesions in the
      white matter were clearly observed on magnetic resonance imaging (MRI) with the
      T2-weighted sequence, and were found to have spontaneously disappeared on
      subsequent MRI performed 7 weeks later. Brain lesions associated with herpes
      simplex encephalitis in the literature are reviewed and the pathogenesis in the
      present case is discussed.

PMID- 8733911
TI  - A Japanese case of infantile sialic acid storage disease.
AB  - We report a 4-year-old Japanese girl with infantile sialic acid storage disease.
      She presented with failure to thrive, coarse facial features, hepatosplenomegaly,
      severe mental retardation and spastic quadriplegia. Electron microscopic
      examination of cultured skin fibroblasts revealed multiple vacuoles and inclusion
      material representing distended lysosomes, thus suggesting a lysosomal storage
      disorder. A high concentration of free sialic acid was present in the urine and
      cultured fibroblasts, but bound sialic acid was not increased. The activity of a
      variety of lysosomal enzymes was not diminished. The MRI findings included brain
      atrophy and a diffuse high signal in the cerebral white matter and low signal in
      the basal ganglia on T2-weighted images. To our knowledge, this is the first case
      of infantile sialic acid storage disease described in a non-Caucasian family.

PMID- 8733912
TI  - Paroxysmal nocturnal hemoglobinuria presenting as moyamoya syndrome.
AB  - We report an 11-year-old girl who has paroxysmal nocturnal hemoglobinuria (PNH)
      and was admitted because of recurrent cerebrovascular accidents (CVA) and
      intermittent hemoglobinuria. Internal carotid angiography revealed bilateral
      typical moyamoya patterns. Although CVA due to arterial thrombosis may occur in
      PNH, the basal moyamoya vessels were never mentioned in case reports yet. The
      moyamoya syndrome has been reported in a variety of diseases and represents the
      nonspecific response to an impairment of arterial flow at specific sites in the
      brain. Our case discloses that PNH may present as moyamoya syndrome.

PMID- 8733913
TI  - Neonatal meningitis caused by Bifidobacterium breve.
AB  - We are reporting a male neonate with meningitis caused by Bifidobacterium breve.
      This is only the second case reported so far to our knowledge. The patient's
      clinical course was excellent and inflammatory indications, such as serum C
      reactive protein, were weak. Although the antibiotics used for the patient were
      effective against this bacterium both in vitro and in vivo, two relapses occurred
      which might have been caused by an incomplete remission due to the low
      permeability of antibiotics through the blood-brain barrier under the very mild
      inflammation of the meninges, and also by the discrepancy between minimum
      bactericidal concentrations (MBC) and minimum inhibitory concentrations (MIC).
      Anaerobic meningitis is very rare, but it may exist in more than the reported
      cases. Anaerobic culture should be performed for patients with culture-negative
      purulent meningitis.

PMID- 8733914
TI  - Genetic immunization.
AB  - Genetic immunization, the latest addition to the field of vaccinology, has shown,
      in a number of animal models, to be an efficacious approach to induce protective
      immunity to infectious diseases. The advantages of DNA vaccines are their ease of
      construction, the low expanse of mass production, their high temperature
      stability, and their ability to induce a full spectrum of exceptionally long
      lasting immune responses including cytolytic T cells. Their potential
      disadvantages are putative safety issues such as integration into the host cell
      genome. The slow development of the immune response to genetic immunization will
      make these vaccines unsuitable for treatment of some infectious disease such as
      postexposure vaccination to rabies virus, where a rapid immune response is
      warranted. Although only time will tell if genetic immunization provides a viable
      alternative for human immunization, in the meantime this approach provides
      immunologists with a powerful tool to gain further insight in the mechanisms that
      drive primary immune responses.

PMID- 8733916
TI  - Serum antibodies to HPV 16 virus-like particles are not associated with penile
      cancer in Chinese males.

PMID- 8733915
TI  - Immunogenicity of bovine herpesvirus 1 glycoprotein D in mice: effect of antigen
      form on the induction of cellular and humoral immune responses.
AB  - For the development of veterinary subunit vaccines, modifications to the antigen
      may be needed to make the production of these vaccines cost effective. To
      investigate the effect of antigen modifications on immune response, we used
      glycoprotein D, one of the major glycoproteins of bovine herpesvirus-1 (BHV-1),
      as a model antigen. We developed a mouse model to assess the immune response
      elicited by immunization with either a recombinant truncated (tgD) or the
      authentic full-length (gD) form of BHV-1 gD in VSA3, a novel water-in-oil
      adjuvant. Both forms of BHV-1 gD antigen induced good levels of cell-mediated
      immunity, as evaluated by antigen-specific proliferative response and cytokine
      (IFN-gamma and IL-4) production. Following primary immunization, the humoral
      immune response induced by gD was superior to that elicited by vaccination with
      tgD. However, after a secondary immunization, a strong and similar antibody
      response to BHV-1 gD was induced by both forms of the antigen. The difference in
      immunogenicity between gD and tgD after primary immunization was not due to the
      loss of immunogenic epitopes in the truncated antigen or the ability to associate
      with the adjuvant VSA3. Our results indicate that both gD and tgD are capable of
      efficiently inducing a cell-mediated immune response, and although recombinant
      tgD is less efficient in inducing a primary humoral immune response when compared
      to the full-length gD, tgD effectively primed for a secondary antibody response.

PMID- 8733917
TI  - Enhancement of human NK and LAK cytotoxicity against HCMV-infected cells by
      rhamnogalacturonan: specificity of reaction.
AB  - Human peripheral blood mononuclear cells (PBMC) and their subpopulations obtained
      from healthy donors were used to study improvement of MHC-unrestricted cytotoxic
      reactions against cells infected with human cytomegalovirus (HCMV) at different
      multiplicities of infection. Natural killer (NK) and lymphokine-activated killer
      (LAK) cytotoxicity against HCMV-infected cells was greatly enhanced in the
      presence of rhamnogalacturonan (500 ng/ml). The increase of the multiplicity of
      infection from MOI 0.1 to 1.0 had only a slight effect on cytotoxicity
      enhancement by rhamnogalacturonan. The chemical specificity of interaction of
      rhamnogalacturonan with effector cells and virus-infected cells was found to be
      analogous to the interaction with tumor cells, i.e., both types of target cells
      must express a receptor for rhamnogalacturonan since rhamnogalacturonan-mediated
      enhancement of NK and LAK cytotoxicity against HCMV-infected cells was similarly
      inhibited by preincubation of CD56+ effector cells with 60% deacetylated D
      mannose pentaacetate.

PMID- 8733918
TI  - Induction of antibodies to the bluetongue virus core polypeptide VP7 in sheep by
      internal image rabbit antiidiotypic antibodies.
AB  - We previously generated rabbit polyclonal antiidiotypic antibody (anti-Id) to a
      murine monoclonal antibody (M1875) specific for the bluetongue virus core protein
      VP7, and demonstrated that this anti-Id (designated RAb2-A) had the
      characteristics of an internal image anti-Id (Ab2 beta). In this communication,
      RAb2-A was used to induce immune responses in sheep and the responses were
      compared to immunization with VP7. The immune sera were tested for the presence
      of anti-VP7 antibodies and the expression of the Id of M1875. Animals immunized
      with RAb2-A were able to produce M1875-like antibody responses, i.e., they
      recognized the same or a similar epitope as M1875 and possessed the M1875 Id,
      without subsequent exposure to the original antigen. This was demonstrated by
      showing that antibodies induced by RAb2-A (i) reacted specifically with the
      immunizing anti-Id, (ii) were capable of binding VP7, (iii) inhibited M1875 from
      binding to VP7, and (iv) inhibited M1875 from binding to RAb2-A. Animals
      immunized with purified VP7 produced antibodies that possessed the epitope and
      idiotope specificity of M1875. No antibody responses to VP7 were detected in
      control animals immunized with either rabbit anti-Id to the pseudorabies virus
      glycoprotein gII or BHK-21 cell proteins. We conclude that rabbit anti-Id RAb2-A
      serologically mimics an M1875-defined VP7 epitope sufficiently to function as a
      surrogate antigen for inducing anti-bluetongue virus VP7 responses.

PMID- 8733919
TI  - Decreased levels of circulating IFN-alpha and increased sCD23 in patients with
      acute infectious mononucleosis.
AB  - Epstein-Barr virus (EBV) is the etiological agent for acute infectious
      mononucleosis (AIM). It is also associated with certain malignant disorders in
      individuals with immunodeficiencies such as B cell lymphoproliferative disorder
      (BLPD). Our previous study with BLPD patients had demonstrated significantly
      higher serum IL-4 and IgE levels and significantly decreased IFN-alpha levels.
      These observations were consistent with the model of regulation of B cell growth
      by T cell-derived cytokines, in which IL-4 promotes B cell growth and switch to
      IgE synthesis whereas IFN-alpha and IFN-gamma inhibit these IL-4 mediated
      effects. Since AIM is also EBV associated, this study was designed to examine IL
      4, IFN-alpha, IFN-gamma, IgE, and soluble CD23 (sCD23) serum levels in AIM
      patients. In this study we report for the first time that in contrast to BLPD
      patients, AIM patients did not exhibit increased levels of IL-4 and IgE; however
      AIM patients to exhibit decreased IFN-alpha levels and, additionally, also
      exhibit significantly higher sCD23 levels. This could result in B cell activation
      and have implications for the survival of the virus in B cells.

PMID- 8733920
TI  - Antibody-dependent enhancement (ADE) of porcine reproductive and respiratory
      syndrome virus (PRRSV) infection in pigs.
AB  - Infection of porcine alveolar macrophages by the porcine reproductive and
      respiratory syndrome virus (PRRSV) was significantly enhanced in vitro by
      antibody raised against the PRRSV isolate ISU-P (p < 0.01). Increased yields and
      infection rates were highly correlated (r = 0.95) and the ratio of yield to
      infection rate was greater than 1.4, suggesting that more than one mechanism was
      responsible for enhanced infection. Antibody-dependent enhancement (ADE) of
      infection was also demonstrated in vivo using a completely randomized block
      design (n = 16). The mean level and duration of viremia were greater (p < 0.05)
      in pigs injected with subneutralizing amounts of PRRSV-specific IgG prior to
      virus challenge than in control pigs injected with normal IgG. In contrast, virus
      replication was significantly (p < 0.01) inhibited in pigs with neutralizing
      antibody titers of 4 log2. The period of time that subneutralizing levels of
      antibody can persist and contribute to ADE of PRRSV infection was estimated in 4
      pigs injected with PRRSV-specific IgG to yield an initial neutralizing antibody
      titer of 3.8 log2. Neutralizing activity declined to undetectable levels by day
      37 postinjection (PI). ADE activity was first detected in undiluted sera on day
      20 PI and persisted through day 62 PI. Western immunoblot analysis of sera
      collected between days 37 and 62 PI detected antibodies specific for the 15-kDa
      nucleocapsid and 26-kDa glycosylated envelope proteins. These results strongly
      suggest that ADE has the potential to contribute to the pathogenesis of PRRSV
      infection and is mediated by antibody specific for the 26-kDa envelope protein.

PMID- 8733921
TI  - Medico-psychological study of a memory disorder. 1889.

PMID- 8733922
TI  - Korsakoff and amnesia.

PMID- 8733923
TI  - Reactivating a reactivation theory of implicit memory.
AB  - Implicit and explicit memory tasks are interpreted within a traditional memory
      theory that distinguishes associations between different classes of memory units
      (sensory features, logogens, imagines, concepts, context tags). Associations from
      specific sensory features to logogens are strengthened by perceptual experiences,
      leading to specific perceptual priming. Associations among concepts are
      strengthened by use, leading to specific conceptual priming. Activating
      associations from concepts to logogens leads to semantic and associative priming.
      Item presentation also establishes a new association from it to a representation
      of the personal context, comprising an "episodic memory." Such contextual
      associations play a major role in explicit memory tasks such as recall or
      recognition. A critical assumption of the theory is that presentation of a given
      item strengthens its sensory and contextual associations independently; this
      permits the theory to explain various dissociations of implicit and explicit
      memory measures. Furthermore, by assuming that brain-injured patients with global
      amnesia have a selective deficit in establishing novel associations to the
      context, the theory can explain their deficits in explicit memory along side
      their intact implicit memory.

PMID- 8733924
TI  - How priming affects two speeded implicit tests of remembering: naming colors
      versus reading words.
AB  - Three experiments investigated two timed implicit tests of memory--word reading
      and color naming. Using the study-test procedure, Experiments 1 and 2 showed that
      studied words caused reliable facilitation in word reading but no interference in
      color naming relative to unstudied words. Indeed, there was a small amount of
      facilitation in color naming as well. Experiment 3 further explored the color
      naming task by alternating shorter study and test intervals and adding controls
      trials consisting of letter strings. Although both studied and unstudied words
      showed interference relative to the control letter strings, the amounts of
      interference they showed did not differ. Overall, word reading consistently
      displayed facilitation whereas color naming never exhibited increased
      interference due to word priming. Priming appears to be process-specific: It is
      restricted to facilitating repetition of processing previously applied to a
      stimulus and does not extend to influencing performance on a different task
      involving the same studied materials.

PMID- 8733925
TI  - Nonverbal local context cues explicit but not implicit memory.
AB  - Memory research distinguishes two components of episodes--the event or item and
      the spatial-temporal setting or context in which it occurred. The word context is
      used either globally to denote the physical, social, or emotional environment at
      study and test or it is used locally to refer to another word or picture that was
      paired with a particular target. In this article, we report four experiments that
      investigated the influence of two different nonverbal local contexts on explicit
      word recognition and implicit word identification test performance. In each
      experiment, university students studied words that were displayed against various
      extra-item local contexts, and the contexts were either the same or different at
      study and test. What differed across experiments was the nature of the contexts:
      for Experiments 1 and 2, it was a band of color that stretched across the
      computer screen, and for Experiments 3 and 4, the context was a colored line
      drawing. The combined findings from all experiments provide no evidence of memory
      context effects (MCE) on priming. By contrast, recognition test performance
      showed reliable MCEs but only when the local context was a concrete drawing or
      when it was a color that was target-related or appropriate. The discussion
      compared these findings with those from previous studies that concerned the
      cueing effectiveness of verbal and nonverbal extra-item contexts.

PMID- 8733926
TI  - Automatic retrieval of new associations under shallow encoding conditions.
AB  - In two experiments during the study phase participants read unrelated context
      target word pairs presented below a line drawing of the context word. During test
      the strong cue group was presented with context words, line drawings, and stems
      of target words. The line drawings were not presented in the weak cue group.
      Stems were paired with the same context words as at study (intact), paired with
      different context words (recombined), or corresponded to unstudied words
      (control). In Experiment 1 participants were instructed to complete stems with
      the first word that came to mind (indirect). The priming effect for new
      associations was twice as large in the strong cue group. In Experiment 2 the
      process dissociation procedure was applied and participants completed stems with
      studied words (inclusion) or with unstudied words (exclusion). Results indicated
      that consciously controlled and automatic retrieval processes mediated the
      associative effect in both groups.

PMID- 8733927
TI  - Noncriterial recollection: familiarity as automatic, irrelevant recollection.
AB  - Recollection is sometimes automatic in that details of a prior encounter with an
      item come to mind although those details are irrelevant to a current task. For
      example, when asked about the size of the type in which an item was earlier
      presented, one might automatically recollect the location in which it was
      presented. We used the process dissociation procedure to show that such
      noncriterial recollection can function as familiarity--its effects were
      independent of intended recollection.

PMID- 8733928
TI  - Levels-of-processing effects on a variety of memory tasks: new findings and
      theoretical implications.
AB  - Three experiments investigated level of processing (LOP) effects on a variety of
      direct and indirect memory tasks, in the context of a processing theory of
      dissociations. Subjects studied words in five encoding conditions and received
      one of ten memory tests. In Experiment 1, four tests previously classified as
      conceptual showed a robust LOP effect, as did a direct perceptual test of
      graphemic cued recall. An indirect perceptual word fragment completion test was
      unaffected by LOP. Experiment 2 showed that a new indirect version of a graphemic
      cued test was not affected by LOP. In Experiment 3, guided by a
      generation/recognition model, we constructed three new direct tests in which
      subjects identified words that were graphemically, phonologically, or
      semantically similar to studied words. The three tests differed in their
      sensitivity to study conditions, but LOP had no effect in any case, despite the
      involvement of deliberate conscious recollection. Contemporary explanatory
      frameworks couched as dichotomies (e.g., implicit/explicit,
      perceptual/conceptual) do not provide an adequate account of the results. It
      seems necessary instead to specify the types of information activated by each
      encoding condition, the types of information required by each test, and how
      encoding and retrieval processes are modified by task instructions.

PMID- 8733929
TI  - Manipulation of attention at study affects an explicit but not an implicit test
      of memory.
AB  - We investigated the impact of attention during encoding on later retrieval.
      During study, participants read some words aloud (ignoring the print color) and
      named the print color of other words aloud (ignoring the word). Then one of two
      memory tests was administered. The explicit test--recognition--required conscious
      recollection of whether a word was studied. Previously read words were recognized
      more accurately than were previously color named words. This contrasted sharply
      with performance on the implicit test--repetition priming in lexical decision.
      Here, words that were color named during study showed priming equivalent to words
      that were read during study; both were responded to faster than unstudied words.
      Thus, an attentional manipulation during study had a strong effect on an explicit
      test of memory, but almost no effect on an implicit test. Focal attention during
      study is crucial for remembering consciously but not necessarily for remembering
      without awareness.

PMID- 8733930
TI  - Continuing influences of to-be-forgotten information.
AB  - In the present paper, we first argue that it is critical for humans to forget;
      that is, to have some means of preventing out-of-date information from
      interfering with the recall of current information. We then argue that the
      primary means of accomplishing such adaptive updating of human memory is
      retrieval inhibition: Information that is rendered out of date by new learning
      becomes less retrievable, but remains at essentially full strength in memory as
      indexed by other measures, such as recognition and word-fragment completion. We
      conclude with a speculation that certain unconscious influences of prior events
      may, in fact, be stronger if those events were to be forgotten rather than to be
      remembered.

PMID- 8733931
TI  - Unconscious gender bias in fame judgments?
AB  - In two experiments the conditions of, and the processes leading to, gender biases
      in fame judgments were investigated. In Experiment 1, the gender bias was not
      reduced in a condition that alerted participants to the gender of the names. In
      Experiment 2, participants' sex-role orientation, but not their gender, was
      related to the gender bias. The process dissociation procedure was used in both
      experiments in an attempt to separate conscious and unconscious memory processes
      contributing to the gender bias. Using L.L. Jacoby's 1991) original measurement
      model there appeared to be evidence for unconscious influences on the gender bias
      in fame judgments. Unfortunately, this evidence disappeared when a model was used
      that takes guessing and, hence, response biases into account, which confirms that
      measurement models that ignore response biases in the process dissociation
      procedure may lead to erroneous conclusions.

PMID- 8733932
TI  - Modeling unconscious gender bias in fame judgments: finding the proper branch of
      the correct (multinomial) tree.
AB  - In the preceding article, Buchner and Wippich used a guessing-corrected,
      multinomial process-dissociation analysis to test whether a gender bias in fame
      judgements reported by Banaji and Greenwald (Journal of Personality and Social
      Psychology, 1995, 68, 181-198) was unconscious. In their two experiments, Buchner
      and Wippich found no evidence for unconscious mediation of this gender bias.
      Their conclusion can be questioned by noting that (a) the gender difference in
      familiarity of previously seen names that Buchner and Wippich modeled was
      different from the gender difference in criterion for fame judgements reported by
      Banaji and Greenwald, (b) the assumptions of Buchner and Wippich's multinomial
      model excluded processes that are plausibly involved in the fame judgement task,
      and (c) the constructs of Buchner and Wippich's model that corresponded most
      closely to Banaji and Greenwald's gender-bias interpretation were formulated so
      as to preclude the possibility of modeling that interpretation. Perhaps a more
      complex multinomial model can model the Banaji and Greenwald interpretation.

PMID- 8733933
TI  - Investigating fame judgments: on the generality of hypotheses, conclusions, and
      measurement models.
AB  - In this article, we try to clarify some of the issues raised by S.C. Draine, A.G.
      Greenwald, and M.R. Banaji (1996) concerning our investigation into the gender
      bias in fame judgments (A. Buchner & W. Wippich, 1996). First, we did not test
      the general hypothesis and did draw the general conclusion that Drain et al.
      suggest we did. Second, we did did not reject M.R. Banaji and A.G. Greenwald's
      (1995) assumptions about the familiarity of male and female names in the fame
      judgment task, but we showed how one could have come to reject it using a
      widespread measurement model for the process dissociation procedure. Third, we
      argue that the processes which Draine et al. suggest should also be included in
      the measurement model we used are probably negligible, and if they are not, then
      the validity of the results of a number of fame judgment experiments must be
      called into question. In general, however, we agree with what seems to be the
      main message of M.R. Banaji and A.G. Greenwald's (1995) research, namely, that
      social categories have to be considered whenever priming is investigated within a
      social domain.

PMID- 8733934
TI  - Response bias correction in the process dissociation procedure: approaches,
      assumptions, and evaluation.
AB  - Buchner, Erdfelder, and Vaterrodt-Plunnecke (1995) advocated an exposition of the
      process dissociation procedure within the framework of multinomial modeling.
      Among the misleading aspects of this exposition is its tendency to obscure the
      overlap between processes. In contrast, clarifying these crucial interactions
      leads to a general classification of response bias corrections to the process
      dissociation procedure. This scheme, in which corrective models are classified on
      the basis of process interactions, clarifies the assumptions underlying
      previously proposed corrections. As an illustration of the framework, three such
      corrections are derived. These corrective models are evaluated by applying them
      to the data reported by Buchner et al. (1995).

PMID- 8733935
TI  - Can we resolve contradictions between process dissociation models?
AB  - Wainwright and Reingold (1996) presented equations for various versions of the
      process dissociation procedure that has been used to separate conscious and
      unconscious memory process. In the present reply it is suggested that these
      equations, though helpful, may not capture some of the key theoretical
      possibilities that could help to resolve apparent contradictions and paradoxes in
      the empirical literature. Specifically, there could be an independence of
      processes that might be estimated to a sufficient degree of accuracy for some
      theoretical purposes despite a violation of the assumption of stochastic
      independence.

PMID- 8733936
TI  - DNA single and double strand breaks induced by aliphatic and aromatic aldehydes
      in combination with copper (II).
AB  - The aliphatic n-butyr-and n-valeraldehyde as well as the aromatic benz- and
      anisaldehyde induced DNA strand breaks in PM2 DNA in the presence of CuCl2.
      Neither aldehydes nor CuCl2 alone showed DNA breakage properties. The maximum of
      single strand breaks (SSBs) induced by the combination of CuCl2 and aldehydes was
      dependent on the CuCl2-concentration. The aliphatic aldehydes induced SSBs and
      double strand breaks (DSBs) at lower concentrations than aromatic aldehydes when
      optimal CuCl2 concentration were used. Catalase and neocuproine nearly completely
      inhibited strand break formation induced by aromatic aldehydes/CuCl2. The
      prevention of strand breaks induced by aliphatic aldehydes/CuCl2 was less
      effective. While the inhibition by neocuproine was only 25%, catalase was totally
      ineffective. In all aldehydes/CuCl2 mixtures the formation of Cu(I) was observed.
      The results point to different DNA damaging species produced during redox
      reactions of aromatic and aliphatic aldehydes in combination with CuCl2.

PMID- 8733937
TI  - Oxidation of low-density lipoprotein by human monocyte-macrophages results in
      toxicity to the oxidising culture.
AB  - Human monocyte-macrophage cultures were exposed to native low density lipoprotein
      (LDL) for up to 24 h in Ham's F10 medium and the extent of cell-mediated LDL
      oxidation was determined by measurement of electrophoretic mobility on agarose
      gels and measurement of lipids and oxidised lipids (including 7 beta
      hydroxycholesterol) by GC. After an initial lag phase, which varied from 2-8 h,
      there was a steady increase in oxidation over 24 h. No-cell control incubations
      showed minimal increases in oxidation over 24 h. Significant toxicity, measured
      as release of radioactivity from macrophages pre-loaded with tritiated adenine,
      was observed in the cells when they oxidised LDL and the extent of radioactivity
      release correlated closely with the extent of LDL oxidation. Inhibition of
      oxidation using alpha-tocopherol or probucol reduced toxicity within the
      oxidising culture. This self-inflicted toxicity may help to explain the origin
      and enlargement of the lipid core of advanced atherosclerotic lesions.

PMID- 8733938
TI  - Permeability of nitric oxide through lipid bilayer membranes.
AB  - Profiles of the local nitric oxide (.NO) diffusion-concentration product across
      the egg yolk phosphatidylcholine membrane in the absence and presence of 30 mol%
      cholesterol were obtained using line-broadening electron paramagnetic resonance
      (EPR) and lipid-soluble nitroxide spin labels. Membrane .NO permeability
      coefficients were calculated from these profiles. At 20 degrees C, values of 93
      and 77 cm/s for membranes in the absence and presence of cholesterol were
      obtained, compared with 73 and 66 cm/s for water layers of the same thickness as
      the membranes. Fluid-phase membranes are not barriers to .NO transport.
      Cholesterol significantly increases .NO transport in the center of the lipid
      bilayer.

PMID- 8733939
TI  - Continuous monitoring of intermediates and final products of oxidation of low
      density lipoprotein by means of UV-spectroscopy.
AB  - The most widely used routine technique for determination of LDL 'oxidizability'
      is the continuous monitoring of the absorption at 234 nm in the UV spectrum of
      LDL, following the addition of an oxidation promotor such as copper ions. This
      absorption is commonly attributed to the conjugated dienes formed upon oxidation
      as the major intermediate, namely the hydroperoxides of polyunsaturated fatty
      acids, mostly linoleate hydroperoxides. These, however, are not the only products
      of oxidation that absorb light at 234 nm. Other products, particularly 7
      ketocholesterol, also absorb light at the same wavelength. Furthermore, enals and
      dienals also absorb in the wavelength range of 210-300 nm. The aim of the present
      work was to develop a simple spectroscopic method for more detailed investigation
      of the kinetics of lipoprotein oxidation. The method is based on continuous
      measurement of the UV spectrum in the wavelength range of 210-300 nm and
      subsequent decomposition of the spectra into four absorption bands due to
      hydroperoxides, 7-ketocholesterol, dienals and enals. The sixth derivatives of
      the spectra, recorded during the first seven hours of copper-induced oxidation of
      LDL were used to monitor the growth and subsequent decay of the hydroperoxides.
      The resultant time course, in conjunction with difference spectra obtained after
      the concentration of these intermediates decay to zero, enabled us to determine
      the spectra of the other oxidation products and, by that, to evaluate their time
      dependencies. Based on these results, we present a series of four simple
      equations that can be used to evaluate the concentrations of the individual
      products of LDL oxidation from UV absorption measurements of the mixtures ar
      merely four different wavelengths. The resultant time dependencies of the
      accumulation of four major products of lipid oxidation are consistent with
      published data obtained through separation and chemical analysis. This simple
      method can be used for more meaningful routine kinetic measurements of lipids
      oxidation.

PMID- 8733940
TI  - Effect of MCI-186 on postischemic reperfusion injury in isolated rat heart.
AB  - MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one) is a newly developed antioxidant
      which has been shown to reduce brain edema in cerebral ischemia through
      inhibition of the lipoxygenase pathway of arachidonic acid. However, its effect
      on myocardial reperfusion injury after prolonged ischemia has not yet been
      demonstrated. We compared the mode of the effect of MIC-186 and recombinant human
      CuZn superoxide dismutase (rh-SOD) in isolated perfused rat hearts subjected to
      60-min ischemia followed by 60-min reperfusion. Left ventricular developed
      pressure (LVDP), necrotic area and the release of creatine phosphokinase (CPK)
      and endogenous CuZn superoxide dismutase (endoge-SOD) were measured to evaluate
      myocardial damage. The decrease in left coronary flow (CBF) was measured as an
      index of the damage of left coronary circulation. MCI-186 (14.5 mg/L) was
      perfused for 10 min in the MCI group and rh-SOD (70 mg/L) was perfused during the
      reperfusion period in the SOD group starting 5 min prior to reperfusion. The
      release patterns of CPK and endoge-SOD were analyzed to elucidate the difference
      in the mode of protection of MCI-186 and rh-SOD. The LVDP remained higher in both
      MCI and SOD groups than that of control (76 +/- 1, 77 +/- 2 and 69 +/- 1% of
      preischemic value, respectively). The necrotic area was significantly attenuated
      in both MCI and SOD groups compared with that in the control group (16 +/- 1, 14
      +/- 1 and 32 +/- 1%, respectively, p < 0.05). Total CPK release was lower in both
      MCI and SOD groups than in the control (78 +/- 7, 100 +/- 2 and 116 +/- 4 x 10(3)
      units/g myocardium respectively). The decrease in CPK release was more marked in
      the MCI group than that in the SOD group (p < 0.05). The reduction in CBF was
      significantly attenuated by the treatment with rh-SOD or MCI-186, but the effect
      was much higher in the SOD group than in the MCI group (69 +/- 5, 58 +/- 2, and
      48 +/- 2% in SOD, MCI and control groups, respectively). The release pattern of
      endoge-SOD was identical to that of CPK and thus this did not distinguish the
      mode of effect of MCI-186 from that of rh-SOD. These results indicate that MCI
      186 reduces reperfusion injury in isolated perfused hearts with prolonged
      ischemia and the effect is more closely related to the reduction of myocyte
      damage than the preservation of the coronary circulation.

PMID- 8733941
TI  - Peroxynitrite mediated oxidation of purine bases of nucleosides and isolated DNA.
AB  - Reaction of nitric oxide with superoxide anion produces the highly reactive
      species peroxynitrite (ONOO-). This compound has been shown to be a strong
      oxidant of lipids and proteins. However, no data are available on its effect on
      DNA, with the exception of the induction of strand breaks. We report the result
      of studies on the reactions of peroxynitrite with the adenine and guanine
      moieties of nucleosides and isolated DNA. The samples were analyzed for 8-oxo-7,8
      dihydro-2'-deoxyguanosine (8-oxo-dGuo),2,2-diamino-4-[(2-deoxy-beta-D-erythro
      pentofuranosyl) amino]-5-(2H)-oxazolone (oxazolone) and 8-oxo-7,8-dihydro-2'
      deoxyadenosine (8-oxo-dAdo). The effects of peroxynitrite treatment were compared
      with those of ionizing radiation in aerated aqueous solution, chosen as a source
      of hydroxyl radicals. At the nucleoside level, both oxidizing conditions led to
      the formation of oxazolone and 8-oxo-dAdo. In addition, evidence was provided for
      the formation of the 4R* and 4S* diastereoisomers of 4-hydroxy-8-oxo-4, 8-dihydro
      2'-deoxyguanosine. The latter dGuo oxidation products were chosen as markers of
      the release of singlet oxygen (1O2) upon reaction of peroxynitrous acid with
      hydrogen peroxide. Oxidation of purine bases was then studied within isolated
      DNA. A significant increase in the level of 8-oxo-dGuo, oxazolone and 8-oxo-dAdo
      was observed within double stranded DNA upon exposure to gamma-radiation.
      Oxazolone and 8-oxo-dAdo were formed upon peroxynitrite treatment but no
      significant increase in the amount of 8-oxo-dGuo was detected. These results
      showed that peroxynitrite exhibits oxidizing properties toward purine moieties
      both in nucleosides and isolated DNA. However, the significant differences in the
      oxidative damage distribution within DNA observed after exposure to gamma
      radiation by comparison with peroxynitrite treatment questions the involvement of
      hydroxyl radicals as the main oxidizing species released by decomposition of
      peroxynitrous acid.

PMID- 8733942
TI  - NA+/K+ ATPase impairment and experimental glycation: the role of glucose
      autoxidation.
AB  - Non enzymatic glycation could be involved in the early impairment of Na+/K+
      ATPase that occurs in sciatic nerve of diabetic rats. In fact, decrease of Na+/K+
      ATPase activity is one of the first alterations showed in experimental diabetic
      neuropathy. In this respect, it is known that in the presence of transition
      metals under physiological conditions, glucose can autoxidize yielding hydrogen
      peroxide (H2O2) and free radical intermediates, which, in turn, inhibit the
      cation pump. Our experiments were designed to determine if glucose autoxidation
      has any relevance in the early steps of Na+/K+ ATPase experimental glycation.
      Compared experiments with and without the sodium borohydride (NaBH4) reduction
      step demonstrated that incubation of brain Na+/K+ ATPase with glucose 6-phosphate
      (G 6-P) and trace metals induced a significant decrease in enzyme activity
      dramatically enhanced by addition of copper (Cu2+). A concomitant production of
      H2O2 was noticed. The presence of diethylenetriaminepentaacetic acid (DTPA), a
      strong metal chelator, completely prevented Na+/K+ ATPase impairment and hydrogen
      peroxide formation. No gross structural and conformational alterations of the
      enzyme can be demonstrated by intrinsic and extrinsic fluorescence measurements.
      Our results suggest that during the exposure of brain NA+/K+ ATPase to glucose 6
      phosphate in vitro (experimental glycation), the decrease in activity can be
      correlated, at lease in the early phases, to metal-catalyzed production of
      oxidative species, such as H2O2, through the glucose autoxidation process, and
      not to glucose attachment to the enzyme. Since plasma hydroperoxides and copper
      appear to be elevated in diabetic patients with complications, our data suggest a
      critical role for oxidative reactions in the pathophysiology of the chronic
      complications of diabetes like neuropathy.

PMID- 8733943
TI  - The copper complex of captopril is not a superoxide dismutase mimic. Artefacts in
      DMPO spin trapping.
AB  - The effect of captopril and of its copper complex on several superoxide-dependent
      reactions used to detect and assay superoxide dismutase activity was studied,
      including pyrogallol and hematoxylin autoxidation and Nitro Blue Tetrazolium
      reduction. In none of these systems were superoxide dismutase-like properties of
      captopril/Cu apparent. Captopril/Cu decreased the yield of DMPO-OH adducts
      generated by KO2 but this effect may be due to the acceleration of the decay of
      the adduct by captopril/Cu.

PMID- 8733944
TI  - Oxidative damage and motor neurone disease difficulties in the measurement of
      protein carbonyls in human brain tissue.
AB  - It has been suggested in the literature that elevated oxidative protein damage,
      measured as protein carbonyls, is present in the nervous system of patients with
      sporadic motor neurone disease (MND). However, the actual reported levels of
      brain protein carbonyls vary over a wide range. We show here that this is
      probably due to the use of the different protocols for the carbonyl assay;
      results differ depending on when the dinitrophenylhydrazine reagent is added and
      at what stage in the procedure protein is assayed for the calculation of
      carbonyls on a unit protein basis. Using a range of different procedures, we were
      unable to confirm reports of elevated protein carbonyls in motor cortex from
      brains of patients with MND. We also measured thiobarbituric acid-reactive
      material in the brain samples using an HPLC-based TBA test in the presence of
      butylated hydroxytoluene. In general, there was no significant elevation of TBARS
      in MND motor cortex. However, four patients showed values higher than any of the
      control patients (both 'normal' control and 'disease control'). There was no
      correlation of TBARS with protein carbonyl values. We suggest that oxidative
      damage in motor cortex in sporadic MND, if it occurs, may be confined to a small
      group of patients and may affect different molecular targets in each patient.

PMID- 8733945
TI  - A pharmacokinetic-pharmacodynamic model of tolerance to morphine analgesia during
      infusion in rats.
AB  - A pharmacokinetic-pharmacodynamic (PK-PD) model was constructed to describe the
      kinetics of tolerance development to morphine-induced antinociception. Tail-flick
      latencies in response to hot water (50 degrees C) were assessed in male Sprague
      Dawley rats exposed to a 12-hr iv infusion of either morphine (1.4 to 3.0 mg/kg
      per hr) or saline. Morphine-induced antinociception, expressed as the percentage
      of maximum possible response (% MPR), peaked after 120 min of infusion and
      decreased thereafter despite sustained systemic morphine concentrations. Both the
      rate and extent of tolerance development increased with increasing
      concentrations; an overall residual effect of approximately 24% MPR was observed
      at the end of the infusion regardless of the steady-state morphine concentration.
      The kinetics of tolerance offset were examined in a separate experiment by
      assessing tail-flick latency 15 min after morphine iv bolus (2 mg/kg) in tolerant
      and control rats. Recovery of response neared completion 18.5 days after a 12-hr
      exposure to morphine (2.0 mg/kg per hr). A PK-PD model was constructed to account
      for the delay in onset of antinociceptive effect and tolerance development
      relative to the blood concentration-time profile. According to this model, both
      the extent and the rate of tolerance development were modulated by the kinetics
      of the drug in the central compartment. Accumulation of a hypothetical
      "inhibitor" acting either as a reverse agonist, a competitive or noncompetitive
      antagonist, or a partial agonist could potentially account for the loss of
      pharmacologic effect in the presence of an agonist. The rate of tolerance
      development predicted from the PK-PD model varied widely (28-fold) depending on
      the type of pharmacologic interaction selected to account for the loss of effect.
      Using the rate of tolerance offset to discriminate between the different models
      (t1/2 offset 5.4 days), onset and offset of tolerance was described accurately by
      postulating that the inhibitor behaves as a partial agonist with low intrinsic
      activity (5.5% MPR) and high binding affinity for the receptor (IC50 15.0 ng/ml).

PMID- 8733946
TI  - Analysis of animal pharmacokinetic data: performance of the one point per animal
      design.
AB  - A simulation study was carried out to determine the impact of various design
      factors on the accuracy and precision with which population pharmacokinetic
      parameters are estimated in preclinical pharmacokinetic studies. A drug given by
      intravenous bolus injection and having mono-exponential disposition
      characteristics was assumed. The factors investigated were (i) number of animals
      sampled at specified times with one observation taken per animal, (ii) error in
      observed concentration measurements, and (iii) doubling the number of
      observations per animal while varying the number of animals. Data were analyzed
      with the NONMEM program, and the least number of animals per time point (where
      each animal supplied one concentration-time point) required for accurate and
      precise parameter estimation was determined. The one observation per animal
      design yielded biased and imprecise estimates of variability, and residual
      variability could not be estimated. Increasing the error in the concentration
      measurement led to a significant deterioration in the accuracy and precision with
      which variability was estimated. Obtaining a second sample from each animal
      practically eliminated bias and facilitated the partitioning of interanimal
      variability and residual intraanimal variability, by introducing information
      about the latter. Doubling the total number of observations per animal required
      using half (i.e., 50) the total number of animals required for accurate and
      precise parameter estimation with the one sample per animal design.

PMID- 8733947
TI  - Lack of presystemic metabolism of nifedipine in the rabbit.
AB  - In humans, oral bioavailability of nifedipine has been reported to be around 60%,
      although the organ(s) contributing to its first-pass metabolism have not been
      determined. The aim of this study was to determine in vivo, in anesthetized and
      conscious rabbits the role of the intestine, liver, and lungs in the first-pass
      metabolism of nifedipine. To assess the extraction of nifedipine by the
      intestine, liver, and lungs, nifedipine was administered before and after each
      organ, and serial blood samples were withdrawn from an artery. In conscious
      rabbits, the systemic clearance of nifedipine injected into a lateral vein of an
      ear was 14.6 +/- 1.6 ml/min per kg, a value that was slightly decreased by
      anesthesia. In anesthetized rabbits, compared to the clearance estimated when
      nifedipine was administered into the thoracic aorta, the administration of
      nifedipine into a jugular vein, into the portal vein, or into the portal vein, or
      into the duodenum did not increase the value of the systemic clearance. In
      conscious rabbits, the clearance of nifedipine estimated when the drug was
      administered into the duodenum, the peritoneum, the portal vein, or into the
      jugular vein was identical to the clearance calculated when the drug was injected
      into the thoracic aorta. In vitro, nifedipine was metabolized in liver and
      intestinal epithelial cells homogenates but not in lungs or kidneys. We concluded
      that in the rabbit, oral nifedipine is not subjected to a first-pass metabolism,
      even though the intestine and the liver may contribute to nifedipine systemic
      clearance.

PMID- 8733948
TI  - A nonparametric subject-specific population method for deconvolution: I.
      Description, internal validation, and real data examples.
AB  - In a pharmacokinetics context deconvolution facilitates the following: (i) Given
      data obtained after intravascular (generally intravenous) input one may estimate
      the disposition function; (ii) given the disposition function and data obtained
      after extravascular administration one may estimate the extravascular to vascular
      input rate function. In general if the data can be represented by the convolution
      of two functions, of which one is unknown, deconvolution allows the estimation of
      the unknown one. Attention has been given in the past to deconvolution and in
      particular to its nonparametric variants. However, in a population context
      (multiple observations collected in each of a group of subjects) the use of
      nonparametric deconvolution is limited to either analyzing each subject
      separately or to analyzing the aggregate response from the population without
      specifying subject-specific characteristics. To our knowledge a fully
      nonparametric deconvolution method in which subject specificity is explicitly
      taken into account has not been reported. To do so we use so-called "longitudinal
      splines." A longitudinal spline is a nonparametric function composed of a
      template spline, in common to all subjects, and of a distortion spline
      representing the difference of the subject's function from the template. Using
      longitudinal splines for input rate or disposition function one obtains a
      solution to the problem of taking subject specificity into account in a
      nonparametric deconvolution context. To obtain estimates of longitudinal splines
      we consider three different methods: (1) parametric nonlinear mixed effect, (2)
      least squares, and (3) two-stage. Results obtained in one simulated and two real
      data analyses are shown.

PMID- 8733949
TI  - A nonparametric subject-specific population method for deconvolution: II.
      External validation.
AB  - A lot of attention has been given in the past to deconvolution and in particular
      to its nonparametric variants. In a companion paper (1), we present a fully
      nonparametric deconvolution method in which subject specificity is explicitly
      taken into account. To do so we use so-called "longitudinal splines." A
      longitudinal spline is a nonparametric function composed of a template spline, in
      common to all subjects, and of a distortion spline representing the difference of
      the subject's function from the template. In this paper we concentrate on testing
      and documenting the performance of this nonparametric methodology in terms of the
      approximation of unknown functions. We simulate population data using parametric
      functions, and use longitudinal splines to recover the unknown functions. We
      consider different estimation methods including (1) parametric nonlinear mixed
      effect, (2) least squares, and (3) two-stage. Methods 2-3 are more robust than
      Method 1, and obtain reliable estimates of the unknown functions. The lack of
      robustness of Method 1 appears to be due to the misspecifications of the
      distribution of the subjects' parameters. Results also suggest that in a data
      rich situation nonparametric nonlinear mixed-effect models should be preferred.

PMID- 8733950
TI  - Accuracy of noncompartmental pharmacokinetic parameters estimated from bolus
      injection and steady-state infusion data.
AB  - A Monte Carlo simulation study was carried out to examine the accuracy of
      parameters derived from curve moments. Impulse response (IR) and washout (WO)
      concentration-time curves, based on a triexponential model, were analyzed by
      numerical integration and regression analysis. Both designs were tested according
      to their robustness to measurement error and model misspecification. Performance
      of the methods was judged using the median error (ME) and the median absolute
      error (MAE) of 1000 simulations. The WO design provided better estimates of mean
      disposition residence time and worse estimates of the normalized variance of
      disposition residence times (CVD2) than its rival. At 20% measurement noise, the
      MAE of CVD2 was less than 13%. The WO design was much more robust to model
      misspecification. Numerical integration performed as good as, or better than,
      regression analysis. Both methods are very sensitive to tail-area error, meaning
      that special attention needs to be paid to this aspect of experimental design.
      This study demonstrates that it is possible to obtain good estimates of higher
      moment parameters in a well-designed experiment.

PMID- 8733951
TI  - Three new residual error models for population PK/PD analyses.
AB  - Residual error models, traditionally used in population pharmacokinetic analyses,
      have been developed as if all sources of error have properties similar to those
      of assay error. Since assay error often is only a minor part of the difference
      between predicted and observed concentrations, other sources, with potentially
      other properties, should be considered. We have simulated three complex error
      structures. The first model acknowledges two separate sources of residual error,
      replication error plus pure residual (assay) error. Simulation results for this
      case suggest that ignoring these separate sources of error does not adversely
      affect parameter estimates. The second model allows serially correlated errors,
      as may occur with structural model misspecification. Ignoring this error
      structure leads to biased random-effect parameter estimates. A simple
      autocorrelation model, where the correlation between two errors is assumed to
      decrease exponentially with the time between them, provides more accurate
      estimates of the variability parameters in this case. The third model allows time
      dependent error magnitude. This may be caused, for example, by inaccurate sample
      timing. A time-constant error model fit to time-varying error data can lead to
      bias in all population parameter estimates. A simple two-step time-dependent
      error model is sufficient to improve parameter estimates, even when the true time
      dependence is more complex. Using a real data set, we also illustrate the use of
      the different error models to facilitate the model building process, to provide
      information about error sources, and to provide more accurate parameter
      estimates.

PMID- 8733952
TI  - Magnetization transfer or spin-lock? An investigation of off-resonance saturation
      pulse imaging with varying frequency offsets.
AB  - PURPOSE: To characterize near-resonance saturation pulse MR imaging on a 1.5-T
      scanner in order to gain insight into underlying mechanisms that alter tissue
      contrast and to optimize the technique for neuroimaging. METHODS: Off-resonance
      saturation pulses were applied to T1-weighted, spin-density-weighted, and T2
      weighted sequences at frequency offsets ranging from 50 Hz to 20,000 Hz down
      field from water resonance. Suppression ratios were determined at each offset for
      phantom materials (MnCl2 solution, gadopentetate dimeglumine, corn oil, water,
      and agar), normal brain structures, and a variety of brain lesions. RESULTS:
      Signal suppression of MnCl2 on T1-weighted images occurred at offsets of less
      than 2000 Hz even though no macromolecules were present in the solution. Only
      those phantom materials and tissues with short or intermediate T1 relaxation
      times and relatively large T1/T2 ratios were sensitive to changing frequency
      offsets. Suppression of brain increased from approximately 20% at 2000 Hz offset
      to approximately 45% when the offset was reduced to 300 Hz. In human subjects,
      the net effect of reducing the frequency offset was to increase T2 contrast on T1
      weighted, spin-density-weighted, and T2-weighted images. Distilled water and
      contrast material did not suppress except at very low offsets ( < 300 Hz). A
      frequency offset of 300 Hz was optimal for maximizing conspicuity between most
      contrast-enhancing lesions and adjacent brain while preserving anatomic detail.
      CONCLUSION: Suppression of MnCl2 indicates that magnetization transfer is not the
      sole mechanism of contrast in near-resonance saturation MR imaging. Spin-lock
      excitation can reasonably explain the behavior of the phantom solutions and the
      increase in T2 contrast of tissues achieved as the frequency offset is decreased
      from 2000 Hz to 300 Hz. Below 300 Hz, saturation is presumably caused by spin-tip
      effects. With our pulse design, an offset of 300 Hz is optimal for many routine
      clinical imaging examinations.

PMID- 8733953
TI  - Measurement of cerebral blood volume via the relaxing effect of low-dose
      gadopentetate dimeglumine during bolus transit.
AB  - PURPOSE: To quantify regional cerebral blood volume (rCBV) on the basis of the
      enhancement of blood proton relaxation rates after intravenous administration of
      gadopentetate dimeglumine. METHODS: A series of sequential MR images on one
      section was recorded during bolus transit with a standard fast low-angle shot
      sequence. The signal-intensity curves were converted into corresponding
      concentration-time curves from which rCBV images were calculated. RESULTS: The
      functional parameter images of rCBV were calculated pixel-by-pixel for two
      patients who had received a 1-second bolus injection of 1 mmol of gadopentetate
      dimeglumine. In a larger series of 62 patients, a mean blood volume of 4.6 +/-
      1.6 vol% was determined for normal brain tissue. CONCLUSIONS: The relaxing effect
      of a contrast agent can be used to determine blood volume quantitatively. The
      results are in agreement with those obtained by nuclear medicine techniques. The
      proposed method requires no special hardware, and can thus be implemented on
      clinical MR scanners.

PMID- 8733954
TI  - Echo-planar MR determination of relative cerebral blood volume in human brain
      tumors: T1 versus T2 weighting.
AB  - PURPOSE: Maps related to relative cerebral blood volume (rCBV) were generated
      with the use of the T1 effects produced by a low-dose bolus passage of
      gadopentetate dimeglumine. The T1 maps were evaluated in a tumor population and
      compared with rCBV maps obtained with T2-weighted measurements. METHODS: Imaging
      was performed in 19 patients with suspected intraaxial brain tumors. For the T1
      rCBV maps, a low-dose bolus of contrast material was given during T1-weighted
      interleaved spin-echo echo-planar MR imaging. This was followed by a second
      injection during serial T2-weighted imaging for generation of the T2 rCBV maps.
      RESULTS: Among patients with low-grade lesions (n = 9), T1-based and T2-based
      rCBV maps showed comparably low rCBV in 7 subjects. In the other 2 patients, with
      confirmed tumor dedifferentiation, elevation of rCBV values was seen on maps
      obtained with both techniques. Among patients with high-grade tumors (n = 10), 4
      had no evidence of recurrence and 6 did have tumor recurrence (confirmed by
      follow-up and positron emission tomography). In patients with the high-grade
      lesions exhibiting conventional contrast enhancement, lesions tended to have
      higher estimated values on T1 rCBV maps than on the T2 rCBV maps. CONCLUSION:
      Although the T1 rCBV maps showed less contrast as compared with the T2 rCBV maps,
      they provided diagnostic information that was comparable to the T2 rCBV maps in
      our series of 19 patients with primary brain tumors.

PMID- 8733955
TI  - Potential of MR methods for measuring cerebral blood volume.

PMID- 8733956
TI  - Endovascular therapy for the carotid blowout syndrome in head and neck surgical
      patients: diagnostic and managerial considerations.
AB  - PURPOSE: To review our institution's recent experience with patients with carotid
      blowout syndrome who were referred for emergency diagnostic angiography and
      endovascular therapy. METHODS: Eighteen consecutive patients who had had surgery
      for cancer of the head and neck and in whom carotid blowout syndrome had occurred
      were referred to our service in accordance with a standardized protocol. RESULTS:
      Twenty-three angiographic pathoetiologic conditions were diagnosed in the 18
      patients; the majority of these were pseudoaneurysms involving various segments
      of the carotid system. Multiple lesions were detected in five patients. Most
      patients were treated by means of permanent balloon occlusion; in 8 patients with
      either multiple lesions or impending rupture requiring flap reconstruction, a
      composite permanent balloon occlusion of the affected carotid system was
      performed. Hyperacute hemorrhages were arrested in all cases. Hemorrhages
      reoccurred in 2 cases, and in 2 patients who had permanent balloon occlusion of
      the internal carotid artery, transient ischemic attacks occurred, which appeared
      to be related to temporary collateral reserve failure. No permanent neurologic
      complications ensued. CONCLUSION: Our recent experience with carotid blowout
      syndrome suggests that this clinical diagnosis represents a heterogeneous group
      of angiographic pathoetiologies that the physician should evaluate carefully
      before proceeding with endovascular therapy. Specific endovascular approaches
      depend on the pathoetiologic mechanism of active or impending hemorrhage and the
      urgency with which intervention is required.

PMID- 8733957
TI  - Histologic effects of collagen-filled interlocking detachable coils in the
      ablation of experimental aneurysms in swine.
AB  - PURPOSE: To assess the histologic changes produced by platinum microcoils with an
      inner core of cross-linked bovine collagen in experimentally induced aneurysms in
      swine, and to assess the feasibility of the system for the delivery of the
      collagen. METHODS: Bilateral pouch aneurysms were created in the side wall of the
      common carotid artery in seven barnyard pigs. Eight aneurysms were treated with
      coils designed with an interlocking detachment mechanism: in four of these, the
      coils had an inner core of collagen; in the other four, the platinum microcoils
      had a similar design but without the collagen mandrel. The packing density of the
      coils within the aneurysm was approximately the same for both types of coils. The
      other six aneurysms were left untreated and served as controls. Angiograms were
      obtained at the time of treatment (2 weeks after the aneurysms were created) and
      at 1, 4, and 8 weeks after treatment. All animals were killed 8 weeks after the
      treatment (10 weeks after the aneurysms were created). Arteries and aneurysms
      were resected en bloc and fixed for histopathologic study. RESULTS: The
      interlocking detachment mechanism worked well. Little difference was noted
      between the two types of coils in their ability to effect complete aneurysmal
      thrombosis (three of four aneurysms treated with collagen-core coils and two of
      four aneurysms treated with conventional coils). The collagen-core coils
      stimulated new collagen formation in areas proximal to the coils, and more
      fibroblasts were noted near the collagen-core coils than near the conventional
      coils. CONCLUSION: Local fibroblast proliferation and collagen production were
      stimulated by heterologous cross-linked collagen embedded in micro-coils in this
      experimental model. Such biologic stimulation holds promise for improving the
      endovascular cure rate of aneurysms in humans.

PMID- 8733958
TI  - Platelet deposition and fibrinogen binding on surfaces coated with heparin or
      friction-reducing polymers.
AB  - The blood-contacting properties of polyethylene coated with a lubricious
      hydrophilic coating; an uncoated polyethylene; or a photoheparin-treated
      polyethylene-negative control sample were compared by measuring fibrinogen
      adsorption, antifibrinogen binding, and platelet attachment from human plasma.
      The polyethylene surfaces coated with a hydrophilic polymer were found to be
      similar to surfaces coated with heparin. Fibrinogen adsorption on the hydrophilic
      coating was 60% lower than adsorption on either the uncoated or heparin-coated
      polyethylene samples. Antifibrinogen binding from buffer to the hydrophilic
      coating was also reduced more than 85% from binding to uncoated polyethylene
      samples. Both the hydrophilic coating and heparin coating showed a reduction in
      platelet attachment by a factor of 100 over the uncoated sample as well as
      significantly reduced platelet activation.

PMID- 8733959
TI  - Use of color power transcranial Doppler sonography to monitor aneurysmal coiling.
AB  - We describe the use of a recently developed technique in the field of color
      Doppler sonography, called power Doppler or color Doppler energy, that produces
      better images of the intracranial arteries than those obtained by conventional
      color Doppler techniques. Color Doppler energy makes it possible to identify
      aneurysms and their relationship to the parent artery, thus allowing one to
      observe how much of an aneurysm remains patent and the condition of adjacent
      arteries during endovascular treatment. We describe the use of this technique
      during the insertion of Guglielmi detachable coils into aneurysms and during
      subsequent follow-up examination.

PMID- 8733960
TI  - Salvage of flow-directed microcatheter after hub failure.
AB  - We describe the use of an epidural catheter adapter to salvage a flow-directed
      microcatheter in situ after fracture of the plastic catheter hub. This technique
      eliminates the need to remove the failed catheters prematurely and enables
      successful delivery of liquid embolic agent into arteriovenous malformations in
      the brain.

PMID- 8733961
TI  - Direct intraoperative sclerotherapy of an aneurysmal bone cyst of the sphenoid.
AB  - A young boy presented with a symptomatic aneurysmal bone cyst of the left great
      wing of the sphenoid bone. Arterial embolization had failed to produce
      thrombosis, and the lesion could not be resected surgically. Direct
      intraoperative sclerotherapy resulted in immediate thrombosis of 80% of the
      volume of the vascular malformation with no progression of symptoms. Two years
      later, the symptoms had completely resolved, and CT scans showed total
      ossification of the lesion.

PMID- 8733962
TI  - Proton MR spectroscopy in acute middle cerebral artery stroke.
AB  - PURPOSE: To investigate the feasibility of performing multisection proton MR
      spectroscopy in patients with acute stroke, and to determine whether this imaging
      technique can depict ischemic or infarcted brain regions. METHODS: Multisection
      proton MR spectroscopy, MR imaging, and MR angiography were performed within 24
      hours of stroke onset (mean, 12 hours) in 12 patients who had had a stroke of the
      middle cerebral artery. Spectra were analyzed from brain regions containing T2
      hyperintensity abnormalities on MR images, from regions immediately adjacent to
      these abnormalities, and from anatomically similar contralateral regions. Areas
      of brain containing lactate were compared with areas of T2 hyperintensities on MR
      images. RESULTS: One data set was discarded because of excessive artifacts from
      patient motion. Regions of T2 hyperintensities on MR images were found to contain
      elevated lactate (all 11 cases) and reduced N-acetyl-aspartate (10 of 11 cases)
      relative to contralateral measurements. Lactate levels in regions adjacent to T2
      hyperintensities were not significantly different from those of infarcted brain.
      On the other hand, N-acetyl-aspartate was significantly lower in regions of
      infarction compared with periinfarct tissue. Areas of brain containing elevated
      lactate significantly exceeded those of T2 abnormality. CONCLUSIONS: Proton MR
      spectroscopy is feasible for imaging patients with acute stroke. In the early
      stages of stroke, tissue containing elevated lactate but no other spectroscopic
      or MR imaging abnormality can be identified. Such regions may represent an
      ischemic zone at risk of infarction.

PMID- 8733963
TI  - Vascular MR contrast enhancement in cerebrovascular disease.
AB  - PURPOSE: To determine the significance of vascular enhancement in stroke patients
      with and without permanent neurologic deficit. METHODS: We prospectively studied
      two groups of patients with spin-echo MR imaging before and after injection of
      gadopentetate dimeglumine. In the patients in group 1 (12 women, 22 men; age
      range, 32 to 76 years), who had permanent neurologic deficit caused by recent
      ischemic brain infarction, we obtained 3 to 13 serial MR images during follow-up
      examination. Group 2 consisted of 26 patients (14 women, 12 men; age range, 54 to
      81 years) with transient neurologic deficit caused by angiographically proved
      high-grade stenosis or occlusion of the internal carotid artery. RESULTS:
      Vascular enhancement was present in 59% of patients in group 1 and in 65% of
      patients of group 2. In group 1, the frequency of vascular enhancement declined
      steadily over several weeks, but it was still present in single cases even after
      3 months. Vascular enhancement correlated positively with the extent of brain
      infarction in group 1 and with the degree of carotid stenosis in group 2.
      CONCLUSION: Vascular enhancement as shown by MR imaging may herald ischemic brain
      infarction and could persist over several weeks in areas that show collateral
      flow after infarction has occurred.

PMID- 8733964
TI  - Diagnosis of middle cerebral artery occlusion with transcranial color-coded real
      time sonography.
AB  - PURPOSE: To determine the usefulness of transcranial color-coded real-time
      sonography in detecting occlusion of the horizontal portion of the middle
      cerebral artery. METHODS: Using transcranial color-coded real-time sonography, we
      measured the end-diastolic flow velocity with incident angle correction and the
      side-to-side ratio of the end-diastolic flow velocity (the end-diastolic ratio)
      in both middle cerebral arteries in 44 patients with or without occlusive
      disease. Cerebral angiography was carried out in all patients before or within 1
      week after sonography. The subjects included 4 patients with unilateral stenosis
      of the extracranial internal carotid artery > or = 75%; ICS group), 6 with
      unilateral occlusion of the extracranial internal carotid (ICO group), 6 with
      occlusion of the horizontal portion of the middle cerebral artery (M1 group), and
      28 without stenotic (< 75%) lesions in the internal carotid artery (control
      group). RESULTS: In the control group, the end-diastolic flow velocity was 40.4
      +/- 16.8 cm/s (mean +/- SD) and the end-diastolic ratio was 1.28 +/- 0.27. In the
      ICS and ICO groups, the end-diastolic flow velocities on the affected side and
      the end-diastolic ratios were 33.4 +/- 9.0 cm/s and 1.35 +/- 0.24, and 29.6 +/-
      10.2 cm/s and 1.67 +/- 0.58, respectively. In the M1 group, the end-diastolic
      flow velocity (16.7 +/- 4.29 cm/s) on the occluded side was significantly lower
      than that in the other groups. The end-diastolic ratio (3.53 +/- 1.47) in the M1
      group was significantly higher than that in the other groups. CONCLUSION: The M1
      group could be easily distinguished from the other groups on the basis of the end
      diastolic ratio. Measurement of the end-diastolic flow velocity and the end
      diastolic ratios in the middle cerebral artery by means of transcranial color
      coded real-time sonography may help to identify an occlusion in the horizontal
      portion of the middle cerebral artery.

PMID- 8733965
TI  - Radiologic-pathologic correlation: meningioma of the optic nerve sheath.

PMID- 8733966
TI  - Potential of T2 relaxation time measurements for early detection of radiation
      injury to the brain: experimental study in pigs.
AB  - PURPOSE: To investigate the MR T2 relaxation time and histologic changes after a
      single-fraction 25-Gy dose of radiation to the brain of pigs. METHODS: The right
      hemisphere of 10 Meishan pigs was irradiated with a single dose of 25 GY at the
      90% isodose, using a 12-MeV electron beam. T2 relaxation time was measured within
      three regions of interest in the brain: those that had received 90%, 70%, and 40%
      of the total dose, respectively. T2 kinetics over time was compared with
      histologic studies. RESULTS: Brain T2 values were noted to increase within the
      irradiated areas. T2 kinetics were analyzed in three phases: an immediate
      transient phase and two long-lasting phases. These two long-lasting phases were
      correlated with the detection of ventricular compression and necrosis,
      respectively. The T2 increase within the 90% region of interest was 19%, 22%, and
      26% for phases I, II, and III, respectively. T2 measurements within other regions
      of interest were not significant. CONCLUSION: Although our results suggest a dose
      threshold for T2 variations, brain T2 values increased after irradiation at a
      level at which disease could not be seen on conventional MR images. This
      illustrates the value of using conventional MR imaging in a quantitative manner
      to assess molecular tissue abnormalities at earlier stages of developing
      diseases.

PMID- 8733967
TI  - Linear measures of atrophy in mild Alzheimer disease.
AB  - PURPOSE: To assess the sensitivity of linear measures of brain atrophy in the
      diagnosis of Alzheimer disease (AD) in the early stages. METHODS: Linear measures
      of regional frontal (Bifrontal index, interhemispheric fissure width), medial
      temporal lobe (interuncal distance, minimum thickness of the medial temporal
      lobe), and hippocampal (hippocampal height, width of the choroid fissure, width
      of the temporal horn) atrophy were made on magnified MR images obtained in 46
      patients with AD (33 with mild severity and 13 with moderate severity) and in 31
      control subjects. Gaussian modeling was used to compute sensitivity with
      specificity set at 95%. Discriminant analysis was used to identify measures
      independently contributing to the ability to discriminate AD patients from
      control subjects. RESULTS: The measure with the best sensitivity in
      discriminating AD patients from control subjects was the width of the temporal
      horn. A compound measure of width of the temporal horn, width of the choroid
      fissure, height of the hippocampus, and interuncal distance could discriminate
      patients with mild AD from control subjects with 86% sensitivity. Cross
      validation in patients with moderate AD confirmed the usefulness of the model
      (81% sensitivity). Measures of hippocampal atrophy alone could discriminate
      patients with mild AD from control subjects with 83% sensitivity; in patients
      with moderate AD, cross validation produced 87% sensitivity. CONCLUSIONS: Linear
      measures of hippocampal atrophy can be a useful adjunct in the routine diagnosis
      of AD, even in its early stages.

PMID- 8733968
TI  - Preoperative grading of glioma malignancy with thallium-201 single-photon
      emission CT: comparison with conventional CT.
AB  - PURPOSE: To compare thallium-201 single-photon emission CT with conventional CT
      in grading the malignancy of gliomas and to determine the reliability of each in
      tumor assessment. METHODS: We studied 37 patients who had gliomas (31 high grade
      and 6 low grade) and compared the CT findings with the thallium-201 index, which
      we defined as tumor uptake relative to the uptake in the contralateral
      hemisphere. RESULTS: Among the high-grade gliomas, we observed a significant
      correlation between breakdown volume of the blood-brain barrier and thallium-201
      uptake. However, 8 of the high-grade gliomas had low thallium-201 uptake, in the
      same range as the low-grade gliomas. Of these, 2 were nonenhancing and the other
      6 showed ring enhancement on CT scans. Analysis of variance showed no significant
      difference in thallium-201 indexes between low-grade gliomas and highly malignant
      (grade II-III) gliomas. Accuracy of thallium-201 imaging was lower (78%) than
      that of CT (84%) in identifying high-grade gliomas. CONCLUSIONS: Damage to the
      blood-brain barrier is a prerequisite for uptake of thallium-201 in gliomas.
      Tumors with central necrotic areas and moderate ring enhancement tend to be
      underestimated when evaluated by means of thallium-201 scintigraphy. The results
      indicate a need for caution when interpreting findings on images obtained with
      thallium-201 single-photon emission CT in preoperative evaluation of brain
      tumors.

PMID- 8733969
TI  - Three-dimensional helical CT angiography of skull base meningiomas.
AB  - PURPOSE: To describe the findings of skull base meningiomas on three-dimensional
      CT angiograms obtained with helical scanning and to evaluate the usefulness of
      this method. METHODS: Fifteen patients who had a meningioma near the skull base
      were examined with helical CT after receiving an intravenous bolus injection of
      contrast material. RESULTS: All meningiomas had either a honeycomb (12 patients)
      or solid (3 patients) pattern of enhancement. Bony structures of the skull base
      and adjacent major arteries that were displaced or surrounded by tumor were also
      evident. CONCLUSION: Three-dimensional CT angiography depicts the relationship
      between skull base meningiomas and neighboring bony and vascular structures
      clearly, quickly, and with minimal risk to the patient.

PMID- 8733970
TI  - Radiation-induced meningioma evaluated with positron emission tomography with
      fludeoxyglucose F 18.
AB  - We describe a patient with radiation-induced meningioma 12 years after cranial
      irradiation for ectopic germinoma. PET scans with fludeoxyglucose F 18 showed a
      high glucose metabolic rate in the meningioma despite a benign histologic
      appearance.

PMID- 8733971
TI  - A choroid plexus papilloma arising from an incidental pineal cyst.
AB  - We report a case of an incidental pineal cyst discovered on MR imaging that
      progressed to a choroid plexus papilloma. The MR features of pineal cysts, the
      difficulty of distinguishing benign cysts from cystic neoplasms, and the
      implications for surgical management are discussed.

PMID- 8733972
TI  - Color Doppler sonography in penetrating injuries of the neck.
AB  - PURPOSE: To determine whether color Doppler sonography can be a sensitive
      alternative to screening arteriography for identifying arterial injury in
      patients with penetrating traumatic neck injuries. METHODS: Fifty-two patients
      admitted to our trauma center with penetrating neck injuries (gunshot wounds and
      lacerations) were examined prospectively with color Doppler sonography, and
      findings were compared with the results of angiography (n = 44), with findings at
      surgery (n = 4), and with clinical status (n = 4). RESULTS: Color Doppler
      sonography correctly detected all serious injuries of the carotid arteries (n =
      6; 5 diagnosed at angiography and 1 at surgery) and all injuries of the vertebral
      arteries (n = 4; all diagnosed at angiography). Sonography missed 1 instance of
      reversible narrowing of the internal and external carotid arteries and did not
      show 2 normal vertebral arteries. CONCLUSION: Color Doppler sonography was as
      accurate as angiography in screening clinically stable patients with zone II or
      III injuries and no signs of active bleeding. Our initial results suggest that in
      the future, sonography may be used as a screening examination for arterial
      lesions in patients with penetrating neck injuries.

PMID- 8733973
TI  - Patterns of anterior spinal canal involvement by neoplasms and infections.
AB  - PURPOSE: To show that retrovertebral extension of neoplastic and infectious
      disease proceeds in a predictable manner, with the anatomic superstructure
      determining the shape of the advancing process. METHODS: We examined 58 patients
      who had neoplastic (n = 44) and infectious (n = 14) processes that caused canal
      compromise. In total, 140 levels were examined by means of MR imaging only (48
      patients), CT only (1 patient), CT plus MR imaging (3 patients), and MR imaging
      plus CT myelography (6 patients). RESULTS: At 136 levels, the retrovertebral
      disease process took the shape of a smoothly marginated, bilobulated mass that
      was broad-based against the posterior surface of the vertebra. Various degrees of
      mass effect were observed: symmetric on 108 levels and asymmetric on 28 levels;
      on 4 levels, expansion of the anterior epidural space was unilobar, reflecting
      unilateral canal invasion. With advanced stages of canal invasion, this
      bilobulated pattern was maintained but there was a tendency toward detachment of
      the midline septum (20 levels). CONCLUSION: The observed patterns are determined
      by the particular anatomy of the anterior epidural space. The shape of the mass
      is imposed by the posterior longitudinal ligament and by the attached lateral
      membranes, with the central tether produced by the attached midline septum. The
      two compartments expand independently.

PMID- 8733974
TI  - Osteochondroma of the thoracic spine: an unusual cause of spinal cord
      compression.
AB  - A 24-year-old man with hereditary multiple exostoses had numbness of the lower
      extremities and difficulty walking. CT displayed a calcified extradural mass
      lesion within the spinal canal at T-8 causing cord compression. MR imaging showed
      it to be contiguous with the upper endplate of T-8, suggesting the diagnosis of
      osteochondroma, a rare cause of cord compression, and distinguishing the lesion
      from a calcified disk fragment.

PMID- 8733975
TI  - The spectrum of brain MR abnormalities in sickle-cell disease: a report from the
      Cooperative Study of Sickle Cell Disease.
AB  - PURPOSE: To define the spectrum of abnormalities in sickle-cell disease,
      including infarction, atrophy, and hemorrhage, that are identified by brain MR
      imaging. METHODS: All MR studies included T1, T2, and intermediate pulse
      sequences. Images were interpreted without knowledge of the clinical history or
      neurologic examination findings. Brain MR imaging was performed in 312 children
      with sickle-cell disease. RESULTS: Seventy patients (22%) had infarction/ischemia
      and/or atrophy, infarction/ischemia was noted in 39 children (13%) who had no
      history of a stroke (the "silent" group). The prevalence rates for silent lesions
      were 17% for sickle-cell anemia and 3% for hemoglobin sickle-cell disease. For
      patients with sickle-cell anemia and a history of cerebrovascular accident,
      infarction/ischemia lesions typically involved both cortex and deep white matter,
      while silent lesions usually were confined to deep white matter. Within the age
      range studied, the prevalence of infarction/ischemia did not increase
      significantly with age, although older patients with lesions had more lesions
      than did younger patients with lesions. CONCLUSIONS: Brain MR imaging showed
      infarction/ischemia in the absence of a recognized cerebrovascular accident in
      13% of patients. The prevalence of these lesions did not increase significantly
      between the ages of 6 and 14 years, suggesting that lesions are present by age 6.
      However, the increase in the average number of lesions per patient with age may
      indicate progressive brain injury.

PMID- 8733976
TI  - Deep gray matter structures in HIV infection: a proton MR spectroscopic study.
AB  - PURPOSE: To evaluate the effects of human immunodeficiency virus (HIV) infection
      on proton metabolites in brain regions carrying the heaviest HIV load. METHODS:
      We used two-dimensional proton MR spectroscopy with a preselected volume at the
      level of the third ventricle to measure N-acetyl-aspartate (NAA) and metabolites
      containing choline (Cho), and creatine (Cr) in the basal ganglia of eight
      cognitively impaired subjects who were seropositive for HIV and eight control
      subjects who were seronegative for HIV. Results are expressed as metabolite
      ratios. RESULTS: In the thalamus and lenticular nuclei, NAA/Cr was not different
      between the two groups. NAA/Cho was decreased in both the thalamus and lenticular
      nuclei of the HIV-positive group compared with the HIV-negative group. Cho/Cr
      tended to be increased in both the thalamus and lenticular nuclei of the HIV
      positive group. CONCLUSIONS: The findings suggest no NAA differences between
      groups, consistent with negligible neuron loss in the region of the brain that
      carries the heaviest HIV load. The trends toward increased Cho/Cr are consistent
      with histopathologic findings of infiltration of subcortical gray matter
      structures with foamy macrophages, microglia, and lymphocytes, or possibly with
      gliosis.

PMID- 8733977
TI  - Cerebral visual impairment in periventricular leukomalacia: MR correlation.
AB  - PURPOSE: To evaluate the involvement of central visual pathways in cases of
      periventricular leukomalacia, and to correlate the neuroradiologic findings with
      the degree of visual acuity. METHODS: The MR brain examinations of 27 preterm
      children affected by cerebral palsy resulting from periventricular leukomalacia
      and without significant ophthalmologic lesions were reviewed retrospectively to
      search for possible involvement of the optic radiations and/or of the calcarine
      cortex. The data were compared with the degree of visual acuity estimated by
      means of the Teller Acuity Cards test. RESULTS: Seventeen (63%) of the 27
      patients had cerebral visual impairment, which correlated strongly with MR
      lesions. Quantitative reduction and signal hyperintensity of the peritrigonal
      white matter and atrophy of the calcarine cortex were present in the more severe
      cases. In two blind patients, an altered MR signal was detected in the lateral
      geniculate bodies. CONCLUSION: This study clearly establishes a relationship
      between specific MR findings and visual impairment in children with
      periventricular leukomalacia. The finding of hyperintensity in the lateral
      geniculate bodies was interpreted as an axonal reaction. MR imaging is useful for
      detecting potential visual impairment and for improving clinical diagnosis.

PMID- 8733978
TI  - Cerebral developmental venous anomalies associated with head and neck venous
      malformations.
AB  - PURPOSE: To study cerebral developmental venous anomalies in patients with
      extensive venous malformations of the head and neck. METHODS: All patients had
      undergone carotid angiography 10 to 15 years previously. Four-vessel cerebral
      angiography was carried out in 40 patients with venous malformations. All
      patients had a physical examination, 16 had CT, and 22 were examined with MR
      imaging. One patient had MR angiography. RESULTS: Eighteen developmental venous
      anomalies were noted in 8 (20%) of 40 patients. Four patients had multiple
      anomalies, and these were bilateral in 1 patient. Developmental venous anomalies
      seen in association with cervicofacial, cutaneous, and mucosal venous
      malformations were remarkable in their absence of neurologic events and
      associated cavernoma; significance of ectatic venous convergence, extension, and
      preponderance of deep drainage routes; and frequency with which they multiple in
      occurrence. CONCLUSION: Developmental venous anomalies have a remarkable
      prevalence of 20% in patients with extensive superficial venous malformations.
      Therefore, it is important to search for a cerebral developmental venous anomaly
      when confronted with a cervicofacial venous malformation.

PMID- 8733979
TI  - A spurious description of hyperfixation of HMPAO.

PMID- 8733980
TI  - False-negative single-photon emission CT in AIDS lymphoma: lack of effect of
      steroids.

PMID- 8733981
TI  - Helical CT angiography for the detection of intracranial aneurysms.

PMID- 8733982
TI  - Sonography of the ventriculus terminalis in newborns.

PMID- 8733983
TI  - Recent advances in antibiotic regimens for the treatment of obstetric-gynecologic
      infections.
AB  - This paper reviews new information on antimicrobial agents for the treatment of
      obstetric-gynecologic infections. The bacteriology of these infections is
      complex, reflecting the bacteria that usually colonize the vagina and cervix. In
      general, these infections are polymicrobial in nature: the most frequently
      isolated microorganisms are gram-negative facultative aerobes, anaerobes,
      Chlamydia trachomatis, and Neisseria gonorrhoeae. Antibiotic regimens that do
      provide coverage of these pathogens showed unacceptably high failure rates. A
      review of the studies recently published confirmed the recommendations of the US
      Centers for Disease Control and Prevention for severe (inpatients) and mild-to
      moderate (outpatients) pelvic inflammatory disease infections. In the case of
      severe infections, two regimens are recommended: a second-generation
      cephalosporin like cefoxitin or cefotetan, plus doxycycline or
      clindamycin/gentamicin. In the case of mild-to-moderate infection, a second- or
      third-generation cephalosporin plus doxycycline, or oral clindamycin plus an oral
      quinolone are recommended. Such studies produce high bacteriologic and clinical
      success rates. New studies indicate that gentamicin may be replaced with a
      monobactam such as aztreonam; this regimen leads to slightly better efficacy and
      less toxicity. The possibility of using clindamycin and a quinolone antibiotic is
      also discussed.

PMID- 8733984
TI  - Clinical presentation and treatment of migraine.
AB  - The pathogenesis of migraine is not completely understood but may involve
      vasodilation of cerebral blood vessels and/or the release of vasoactive
      neuropeptides (ie, norepinephrine) from the perivascular axons in the dura mater
      after activation of the trigeminovascular system. Many environmental factors and
      physiologic influences may provoke a migraine or increase its severity. The
      typical migraine headache without aura is unilateral, pulsating, of moderate-to
      severe intensity, and aggravated by physical activity. Migraine prevention is
      best achieved by avoidance of known migraine triggers or enhancers and by
      reducing the amount of lifestyle stressors. Pharmacotherapeutic options in the
      treatment of migraine are discussed herein.

PMID- 8733985
TI  - Stability and compatibility of admixtures of intravenous ciprofloxacin and
      selected drugs.
AB  - The stability and compatibility of ciprofloxacin with selected drugs in
      intravenous admixtures were studied. Ciprofloxacin 2 mg/mL in 5% dextrose was
      combined with each of 22 other drugs at concentrations commonly used in clinical
      practice. Each combination was maintained at room temperature (approximately 22
      degrees C) in constant fluorescent light. Immediately after preparation and at 6
      and 24 hours, each admixture was examined visually in normal fluorescent room
      light and the pH value was determined. For samples lacking visible precipitates
      or having pH changes of not more than 1 unit, ciprofloxacin concentration was
      assayed by using high-performance liquid chromatography. When combined with
      ciprofloxacin, 14 of the study drugs did not alter the concentration of
      ciprofloxacin, including amikacin sulfate, atracurium besylate, aztreonam,
      cimetidine hydrochloride, dobutamine hydrochloride, fluconazole, gentamicin
      sulfate, metronidazole (intravenous, ready to use), midazolam hydrochloride,
      norepinephrine bitartrate, pancuronium bromide, potassium chloride, tobramycin
      sulfate, and vecuronium bromide. There were five drugs that were determined to be
      incompatible with ciprofloxacin because of precipitate formation (amphotericin B,
      ampicillin sodium/sulbactam sodium, cefuroxime sodium, piperacillin sodium, and
      sodium bicarbonate). Incompatibility with ciprofloxacin based on pH changes of
      more than 1 unit was found with four drugs: ampicillin sodium/sulbactam sodium,
      ceftazidime, metronidazole hydrochloride (powder only), and ticarcillin
      disodium/clavulanate potassium. Intravenous ciprofloxacin 2 mg/mL admixed in 5%
      dextrose was stable and compatible with 14 of the 22 test drugs for up to 24
      hours at room temperature. The other eight drugs should not be combined with
      ciprofloxacin.

PMID- 8733986
TI  - The use of alprostadil sterile powder in a home self-injection study of Asian men
      with erectile dysfunction.
AB  - This study evaluated the individual optimal dose of alprostadil in the office
      setting that could be used as the basis for effective home self-injection
      therapy. The study included 150 Asian men with erectile dysfunction (ED). The
      mean age of study participants was 48.3 years (range, 21 to 74 years), and the
      mean duration of ED was 3.6 years. The most common cause of ED was venogenic
      (24%), psychogenic (21%), arteriogenic (13%), neurogenic (0.7%), or a combination
      of these (41%). An optimal response was seen in 72% of patients (n = 108) in the
      office and 96% of patients (n = 100) at home. The mean +/- SD office dose of
      alprostadil was 19.4 +/- 12.8 micrograms versus 18.0 +/- 12.2 micrograms at home.
      More than half of the patients (57% in an office setting and 53% at home)
      achieved an optimal response at a dose between 5 and 15 micrograms. By the 20
      micrograms dose, 82% of patients had achieved an optimal dose at home compared
      with 70% of patients in the office. An optimal response was seen at the same dose
      in the office and home in 75% of patients; the dose at home decreased from the
      office dose for 16% of the patients and increased for 9%. There were 24 patients
      who experienced adverse events: penile pain after injection (18 patients), cold
      sweating (2 patients), pediculosis (1 patient), broken leg (1 patient), ankle
      pain (1 patient), and prolonged erection (1 patient). One patient discontinued
      the study because of penile pain. Alprostadil sterile powder offered safe and
      effective treatment of ED for home self-injection therapy. Once an optimal dose
      response had been established in the physician's office, further home adjustments
      were needed in 25% of patients. Penile pain, usually mild, was the most common,
      possibly related adverse effect reported.

PMID- 8733987
TI  - Placebo-controlled, double-blind study of the efficacy and safety of
      triamcinolone acetonide aerosol nasal inhaler in pediatric patients with seasonal
      allergic rhinitis.
AB  - Triamcinolone acetonide (TAA) aerosol nasal inhaler has been shown to effectively
      relieve the symptoms of seasonal allergic rhinitis in adults and adolescents. We
      conducted a study to evaluate the efficacy and safety of once-daily
      administration of TAA aerosol nasal inhaler in pediatric patients aged 6 to 11
      years with grass seasonal allergic rhinitis. This multicenter, randomized, double
      blind, placebo-controlled, parallel-group study enrolled 116 children who were
      treated with either TAA aerosol nasal inhaler (220 micrograms/d) or placebo once
      daily for 2 weeks. Patients evaluated the severity of rhinitis symptoms (nasal
      stuffiness, discharge, sneezing, and itching) daily according to a four-point
      scale (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Patients' and
      physicians' global evaluations of overall treatment efficacy were assessed at the
      end of the 2-week treatment period. Patients treated with TAA aerosol nasal
      inhaler had significantly greater reductions in all nasal symptom scores overall
      and in virtually all symptoms at the end of week 1 and week 2 compared with those
      in the placebo group. Both patients' and physicians' global evaluations of
      efficacy favored TAA aerosol nasal inhaler over placebo. This study demonstrated
      that once-daily administration of 220 micrograms of TAA aerosol nasal inhaler was
      well tolerated and effectively reduced the symptoms of seasonal allergic rhinitis
      in pediatric patients.

PMID- 8733988
TI  - Penetration of loracarbef into the maxillary sinus: a pharmacokinetic assessment.
AB  - Loracarbef, a beta-lactam antibiotic of the carbacephem class, is active in vitro
      against pathogens associated with acute maxillary sinusitis. To study the extent
      and duration of maxillary sinus fluid penetration after administration of
      loracarbef, 20 patients (10 men, 10 women; average age, 41 +/- 13 years) with
      acute sinusitis were treated with loracarbef 400 mg every 12 hours for 10 days. A
      lavage catheter was inserted into the maxillary sinus, and 150-microL sinus fluid
      samples were obtained at 0 (baseline), 0.5, 1, 1.5, 2, and 2.5 hours after the
      first dose and at 24 and 48 hours (12 hours after the second and fourth doses,
      respectively). Venous blood samples were obtained at the same times. Maxillary
      fluid and serum samples were frozen immediately at -20 degrees C to -70 degrees C
      until later bioassay using a direct agar diffusion method. Excluding missing data
      or inappropriately timed samples, the mean (+/- SD) sinus fluid concentrations
      were 0.16 +/- 0.12 microgram/mL at baseline, 0.23 +/- 0.17 microgram/mL at 0.5
      hour, 1.11 +/- 1.44 micrograms/mL at 1 hour, 1.63 +/- 2.07 micrograms/mL at 1.5
      hours, 1.75 +/- 2.01 micrograms/mL at 2 hours, and 1.60 +/- 1.96 micrograms/mL at
      2.5 hours after dose. The mean sinus fluid concentration before the third dose
      (approximately 12 hours after the second dose) was 1.01 +/- 0.89 microgram/mL and
      before the fifth dose (approximately 12 hours after the fourth dose) was 0.88 +/-
      0.90 microgram/mL. Taking the highest sinus fluid concentration measured in each
      patient, the mean peak sinus fluid concentration was 2.12 +/- 1.98 micrograms/mL
      (range, 0 to 6.7 micrograms/mL). The pretherapy peripheral leukocyte count
      appeared to have a statistically significant association (P < 0.01) with
      loracarbef sinus fluid penetration as estimated by the sinus fluid area under the
      concentration-time curve at 0 to 2.5 hours. Loracarbef 400 mg twice daily
      achieved sinus fluid concentrations that appeared to exceed the minimum
      concentration required to inhibit 90% of relevant acute sinusitis pathogens
      throughout the 12-hour interdose interval in most patients with acute maxillary
      sinusitis.

PMID- 8733989
TI  - Magnesium utilization survey in selected patients with diabetes.
AB  - Patients with diabetes mellitus were surveyed to determine magnesium utilization
      and supplementation patterns and the extent to which these patterns correlate
      with American Diabetes Association (ADA) consensus panel recommendations.
      Participating ADA member physicians were asked to enroll five or more patients
      with insulin-dependent diabetes mellitus (IDDM, or type I diabetes) or non
      insulin-dependent diabetes mellitus (NIDDM, or type II diabetes) who were not
      currently receiving magnesium supplementation and who they believed required or
      could benefit from oral magnesium chloride administration. Data were then
      collected regarding specific patient characteristics (ie, current diabetes
      therapy and glucose control); concomitant diseases and cardiovascular
      medications; baseline serum magnesium level, if measured before initiating
      magnesium chloride supplementation; and magnesium chloride dosage and duration. A
      total of 199 patients with diabetes began treatment with magnesium chloride
      supplementation after enrollment by a specialist. The mean baseline serum
      magnesium level for patients with IDDM was 1.48 mg/dL and for patients with NIDDM
      was 1.44 mg/dL (normal range, 1.80 to 2.40 mg/dL). No differences in mean serum
      magnesium levels were observed between men and women and between those with IDDM
      and those with NIDDM. Glucose control, as measured by glycosylated hemoglobin
      Alc, did not correlate with magnesium serum levels. A concomitant cardiovascular
      disease was present in 70% of patients. In 78.3% of patients, supplementation was
      initiated because of low serum magnesium levels; in 21.7%, magnesium chloride
      therapy was initiated empirically. No correlation was found between serum
      magnesium levels and the prescribed dosage or the recommended duration of
      magnesium therapy. Patterns of magnesium utilization among survey respondents
      generally followed ADA consensus panel recommendations. A majority of diabetic
      patients who were given magnesium chloride supplementation had concomitant
      cardiovascular disease. Primary care physicians and cardiologists who treat large
      numbers of patients with diabetes and cardiovascular disease should be
      knowledgeable of the ADA consensus report because of the high prevalence of
      hypomagnesemia and because of the consequences of magnesium deficiency in these
      high-risk groups. To achieve successful long-term maintenance in these patients,
      additional physician education appears to be necessary regarding initial dosing
      strategies and recommended duration of supplementation.

PMID- 8733990
TI  - Bacteriologic profile and drug resistance in pediatric patients with symptomatic
      bacteriuria.
AB  - The bacteriologic profile in 1081 pediatric patients with culture-positive
      symptomatic bacteriuria was studied over a 30-month period in a 500-bed acute
      care hospital in Riyadh, Saudi Arabia. Microbial isolates were considered
      significant if their numbers equaled or exceeded 10,000 colony-forming units/mL
      in symptomatic patients. Escherichia coli was the most common causative agent of
      urinary tract infections (55.1%), followed by Pseudomonas aeruginosa (11.9%),
      Klebsiella pneumoniae (10.0%), and Enterococcus species (6.1%). Results of
      antimicrobial susceptibility testing indicated that nitrofurantoin and cephradine
      may be used as empiric therapy pending laboratory investigation; gentamicin can
      be added in the treatment in severely ill inpatients, and treatment can be
      modified when microbiologic results become available.

PMID- 8733991
TI  - Drug therapy in multiple sclerosis: a study of Nova Scotia senior citizens.
AB  - We conducted a study to determine the types and costs of drugs used by Nova
      Scotia senior citizens with multiple sclerosis (MS) compared with the types and
      costs of drugs used by all senior citizens in Nova Scotia. Administrative claims
      databases from the Nova Scotia Seniors Pharmacare program for persons aged 65
      years or older were linked to the Dalhousie Multiple Sclerosis Research Unit
      (DMSRU) clinical database (1980-1994). Analyses compared persons with MS aged 65
      years or older who attended the DMSRU at least once with the general population
      of senior citizens. Not all persons with MS attended the DMSRU. In aggregate,
      Pharmacare costs in 1993-1994 for patients with MS aged 65 years or older (N =
      52) were $975.00 Canadian per capita compared with $590.00 Canadian for all
      senior citizens in Nova Scotia (N = 108,646). Thus average drug costs for the
      senior citizens with MS were 65% greater than those for all senior citizens
      covered by Nova Scotia's comprehensive, publicly funded Pharmacare program.
      Compared with other senior citizens, those with MS more frequently received alpha
      blockers, anticholinergics, cholinergics, tricyclic antidepressants,
      anticonvulsants, antifatigue agents, antispasticity agents, and antibiotics for
      bladder infections.

PMID- 8733992
TI  - Cost of acid peptic disorders in a managed-care organization.
AB  - The purpose of this study was to determine the cost of managing ambulatory
      patients with symptoms of acid peptic disorders in a managed-care organization
      under actual clinical conditions. Study data were collected in a large
      independent practice association model health maintenance organization in
      Gainesville, Florida, from prescription records maintained in a computerized
      database and from patient medical records. Patients had to be started on a
      histamine2-receptor antagonist (H2RA) or the proton pump inhibitor omeprazole
      between 1992 and 1994. A total of 113 patients qualified for inclusion in the
      study; 57 received H2RAs, 27 received omeprazole, and 29 received combination
      therapy. The costs of procedures, physician visits, and drug therapy were
      considered in the economic evaluation. Costs were evaluated using two methods:
      the capitation total cost (CTC) and the fee-for-service total cost (FSTC). The
      mean CTC and FSTC for managing a patient with acid peptic symptoms for 6 months
      were $382 +/- 356 (range, $14 to $1820) and $456 +/- 368 (range, $52 to $1925),
      respectively. Drug costs represented 52% of the total FSTC and 62% of the total
      CTC. Drug costs were followed by the costs for encounters with primary care
      physicians, endoscopy, referral to specialists, and upper gastrointestinal (UGI)
      tract procedures. Documented outcomes were available for 85 patients. Compared
      with patients receiving H2RAs (n = 41), patients receiving omeprazole (n = 18)
      had significantly lower FSTCs ($317 +/- 219 compared with $423 +/- 307,
      respectively); diagnostic testing costs (for endoscopy, $0 compared with $44 +/-
      119, respectively; for UGI procedures, $22 +/- 42 compared with $55 +/- 54,
      respectively); physician encounter costs ($66 +/- 40 compared with $86 +/- 38,
      respectively); and referral to specialist costs ($0 compared with $18 +/- 60,
      respectively). Patients receiving omeprazole also had more positive clinical
      outcomes than patients receiving H2RAs (78% compared with 49%, respectively),
      resulting in a more favorable cost of producing a successful outcome compared
      with patients receiving an H2RA. The cost of success was $407 for patients
      treated with omeprazole compared with $869 for patients treated with H2RAs. The
      findings of this analysis conducted under actual clinical conditions support
      findings of randomized clinical trials showing the cost-effectiveness of proton
      pump inhibitors.

PMID- 8733993
TI  - A comparison of costs and efficacy of intranasal fluticasone propionate and
      terfenadine tablets for seasonal allergic rhinitis.
AB  - This paper compares cost-efficacy ratios for intranasal fluticasone propionate
      and terfenadine tablets within a sample of patients with seasonal allergic
      rhinitis symptoms due to mountain cedar allergy. Efficacy was assessed using
      secondary data analysis of patient ratings of symptoms and their overall
      assessment of response to treatment within a previously conducted clinical trial.
      Costs include direct costs of the drugs used for therapy. Patients with
      documented mountain cedar allergy who were 12 years of age or older (N = 232) had
      been randomized to either receive intranasal fluticasone propionate, terfenadine,
      or placebo. The cost-efficacy ratios for intranasal fluticasone propionate 200
      micrograms once daily were more favorable than the ratios for terfenadine 60 mg
      twice daily. This relationship remained throughout the sensitivity analysis.
      Because intranasal fluticasone propionate is only available in a fixed package
      size, the number of efficacy-adjusted days of terfenadine therapy that could be
      purchased to reach break-even costs for a 30-day supply of fluticasone was
      calculated. Cost efficacy-adjusted days ranged from 11 to 18 days. If cost
      efficacy adjustments are not conducted, the upper end of the range increases from
      18 to 22 days, since 22 days of terfenadine could be purchased for the price of a
      30-day supply of intranasal fluticasone propionate. Depending on which of the
      efficacy measures the reader believes, if patients use terfenadine for longer
      than 11 to 22 days, fluticasone propionate is the more cost-efficacious choice.
      Because most allergies are seasonal and allergy seasons typically last longer
      than 11 to 22 days, it is likely that fluticasone propionate will frequently be
      the more cost-efficacious choice in the patient population represented in this
      study.

PMID- 8733994
TI  - Cost-effectiveness of venlafaxine for the treatment of major depression in
      hospitalized patients.
AB  - The economic burden of depression is often underestimated, especially when both
      the direct and indirect costs of treating the disease are considered. The costs
      associated with antidepressant drug therapy are often the focus of efforts to
      reduce overall treatment costs, but in actuality they represent only 10% of the
      overall economic costs of depression. Thus, in analyses of the costs of
      depression, other factors-including hospitalization, physician costs, monitoring,
      and indirect costs associated with lost productivity and comorbidity-are
      important. Economic assessments comparing different antidepressant classes have
      often found that newer antidepressants are more cost-effective than older, less
      expensive drugs because of improved tolerability or efficacy. Venlafaxine
      represents the newest class of antidepressants and offers potential pharmacologic
      benefits, including early onset of action, dose flexibility, broad range of
      activity, and improved tolerance. In one analysis that used the results from a
      study of 67 hospitalized depressed patients, venlafaxine was estimated to result
      in a cost savings of 11.3% versus fluoxetine. These findings support the concept
      that the overall costs of depression are more important than the drug costs in
      determining the cost-effectiveness of therapy.

PMID- 8733996
TI  - Immunopathogenesis and detection of HIV infection in women and newborns.

PMID- 8733997
TI  - Epidemiology of HIV infection in women and newborns.

PMID- 8733998
TI  - Routine voluntary antepartum HIV antibody counseling and testing: a sound public
      health prevention strategy.
AB  - Routine voluntary antepartum HIV antibody counseling and testing are important
      HIV prevention strategies based on sound public health principles. The ultimate
      goal of this testing strategy is two-fold: identification of high-risk
      seronegative women for risk reduction counseling; and identification of HIV
      infected parturients for counseling, prenatal care, and long-term medical
      management. To achieve these objectives, there must be nationwide implementation
      of the CDC HIV prenatal testing guidelines. Our challenge as healthcare providers
      is to ensure that all of our prenatal patients are afforded the opportunity to
      have HIV counseling and testing performed.

PMID- 8733999
TI  - Substance abuse and HIV pregnancy.
AB  - Substance abuse is a significant risk factor for HIV in pregnancy. Most
      substances can have deleterious effects on perinatal outcome, and in pregnancies
      complicated by maternal HIV infection, substance abuse may contribute to the rate
      of vertical transmission and the progression of maternal disease. Therefore,
      pregnant substance-abusing women should be identified and targeted for HIV
      counseling and testing. In addition, drug rehabilitation should be strongly
      advocated. In populations with high prevalences of substance abuse and HIV
      infection, exceptional measures such as voluntary routine drug screening and
      needle exchange programs at the site of prenatal care may be considered. Future
      research is required to understand the relationship among the type, severity, and
      stage of drug addiction and the difference in risk-taking behavior as it relates
      to HIV transmission. Intervention studies must be designed, implemented, and
      evaluated to identify the most effective strategy for managing pregnant substance
      abusers who are exposed or at risk of exposure to HIV.

PMID- 8734000
TI  - Reproductive decision-making and determinants of contraceptive use in HIV
      infected women.
AB  - Perinatal transmission and reproductive decisions of HIV-infected women can be
      categorized in statistical and epidemiological terms. These reports and figures,
      however, do little to fully explain the complexities of human relationships, life
      experiences, personal and cultural influences, and situational and environmental
      variables that impact on the HIV-infected woman regarding reproductive decision
      making. It is only with genuine attempts to understand the woman's perspective
      and the dynamic and unique variables that influence reproductive decision-making,
      as well as maintaining a non-judgmental and culturally sensitive perspective, can
      we hope to assist women, and society as a whole, in coming to terms with the
      complexities of HIV and reproductive decision-making. Further study is needed to
      identify factors that influence reproductive decision-making in HIV-infected
      women. The determinants of contraceptive use regarding demographic factors,
      barriers to contraceptive use, and factors that contribute to successful
      contraceptive use in this population must be understood if efforts to reduce the
      number of unplanned pregnancies are to be successful. More conclusive data are
      needed on the safety and efficacy of oral contraceptives in HIV-infected women as
      well as data that describe the effects of longer acting hormonal contraceptives
      such as levonorgestrel implants (Norplant; Wyeth-Ayerst, Philadelphia, PA) and
      injectable medroxyprogesterone acetate (Depo Provera; Upjohn Company, Kalamazoo,
      MI). More research is needed to determine the effects of patient education and
      counseling and closer follow-up on effective long-term contraception in HIV
      infected women.

PMID- 8734001
TI  - Management of HIV infection for the childbearing age woman.

PMID- 8734002
TI  - The role of antiretroviral therapy in the management of HIV infection in women.

PMID- 8734003
TI  - Determinants of perinatal HIV-1 transmission.

PMID- 8734004
TI  - The diagnosis and management of perinatal HIV infection.

PMID- 8734005
TI  - Common ethical dilemmas encountered in the management of HIV-infected women and
      newborns.
AB  - The clinical management of the HIV-infected pregnant woman and newborns involves
      multifaceted ethical challenges. We have argued that rights-based approaches,
      based on a civil rights model, are not adequate to clinically address these
      challenges. We have argued instead for a more nuanced ethical framework that
      emphasizes the beneficence-based obligations of the physician of the pregnant
      woman, to the fetal patient, and to the newborn, as well as the beneficence-based
      obligations of the pregnant woman to the fetal patient and to the newborn. The
      ethical principle of respect for autonomy shapes the counseling process about
      termination of pregnancy, contraception, and advance directives.

PMID- 8734006
TI  - New applications of mifepristone (RU 486). Foreword.

PMID- 8734007
TI  - Progesterone receptors: expression and regulation in the mammalian ovary.
AB  - The authors have briefly discussed the molecular structure, regulation, and
      function of progesterone receptors in the mammalian ovary. Particularly important
      is the contrast in the regulatory mechanisms of PR induction in the ovary
      (gonadotropins/membrane receptor mediated) and other well-known progesterone
      target tissues, such as the uterus and mammary gland (estrogen/nuclear receptor
      mediated). Future research will focus on how the PR gene responds to these
      hormonal regulatory signals in this cell-specific manner. Equally important in
      this discussion has been the mounting evidence indicating that PRs are an
      essential component of the ovulatory process. The observation that PR-/- knockout
      mice are incapable of undergoing ovulation, even in response to gonadotropin
      challenge, further supports the previous physiological evidence indicating that
      PRs in preovulatory follicles are induced before, and are necessary for,
      ovulation. Further studies are required to determine the identity of PR-regulated
      target genes during the periovulatory period. Although our knowledge of PR
      structure, regulation, and function has increased dramatically during the past
      decade, many exciting questions remain related to the regulation and function(s)
      of PRs in the ovary and other tissues.

PMID- 8734008
TI  - Mifepristone: clinical pharmacology.

PMID- 8734009
TI  - Mifepristone: clinical application in general gynecology.

PMID- 8734010
TI  - Mifepristone: a potential contraceptive.
AB  - Use of standard estrogen-progestin contraception remains problematic in several
      subgroups of patients (e.g., those in whom exogenous estrogens are
      contraindicated, such as survivors of hormone-dependent cancer, or patients with
      endometriosis or uterine fibroids). In addition, the postcoital contraception,
      even if already available, remains at least underused. Additionally, continuous
      intake of contraceptive steroids is under increasing scrutiny. Would
      antiprogestins, and specifically the applications of mifepristone such as the
      ones reviewed in this article offer significant improvements at such problematic
      occasions? The most attractive novel contraceptive application of mifepristone is
      that of emergency postcoital contraception after unprotected intercourse. In
      addition, various options in the endometrial category, specifically those
      requiring drug administration only during a limited time, might be used in the
      future. Mifepristone might offer contraceptive and therapeutic relief to patients
      suffering from endometriosis or uterine fibroids, both conditions that have been
      shown to benefit from mifepristone therapy. However, the use of mifepristone in
      contraceptive preparations that are widely available would pose an additional
      problem of possible misuse of the compound, the reason for currently limiting
      access to mifepristone. However, such risk should be easily avoidable in the case
      of postcoital contraception in which only one dose of mifepristone is needed.
      Regarding the future of mifepristone, and more broadly that of antiprogestins in
      contraception, the authors believe that they will have a place in the future
      contraceptive armament. As already emphasized, the strongest clinical areas are
      those of immediate postcoital and endometrial contraception. Additional studies
      evaluating parenteral modes of administration, the long-term endometrial effects,
      and safety and metabolic effects of prolonged antiprogestin administration are
      needed before mifepristone can be considered a part of the contraceptive arena.

PMID- 8734011
TI  - Mifepristone: cervical ripening and induction of labor.

PMID- 8734012
TI  - Mifepristone and first trimester abortion.

PMID- 8734013
TI  - Mifepristone and ovarian function.
AB  - In summary, RU 486 has been a powerful instrument in delineating progesterone
      action on the ovary. However, early experiments using RU 486 must be interpreted
      with the understanding that systemic administration of the antiprogestin may have
      had extraovarian sites of action, such as at the hypothalamic-pituitary axis or
      at the adrenal, that in turn led to indirect ovarian responses. Treatment with
      progesterone, agonist, or antagonist at periods during which the ovary lacks
      progesterone receptors would further suggest extraovarian sites of action or
      nongenomic mechanisms of action. Furthermore, the dose of ligand or antagonist
      administered and the hormonal milieu at the time of administration may dictate
      the ovarian response (Espey L, personal communication). For example, low doses of
      exogenous progesterone may elicit a biologic response, whereas high doses are
      without effect or may inhibit the biologic effect observed at lower doses.
      Although RU 486 is classically described as an antiprogestin, agonist actions
      have been observed in addition to its the well documented antiglucocorticoid
      effects. All of these variables may contribute to the confounding observations of
      progesterone and RU 486 action on the ovary. Regardless of these caveats,
      experimental paradigms have demonstrated that RU 486, either indirectly or
      directly, regulates ovarian folliculogenesis, stimulates and/or inhibits
      steroidogenesis depending on the species and time of RU 486 administration,
      inhibits ovulation, and modulates luteal function. These findings supports a
      progesterone-dependent mechanism in these varied aspects of ovarian function.

PMID- 8734014
TI  - Mifepristone: antineoplastic studies.

PMID- 8734015
TI  - Mifepristone: treatment of Cushing's syndrome.
AB  - Mifepristone is a potent antagonist of glucocorticoid and progesterone receptors.
      It is the only drug administered to humans with these actions. Exploration of
      mifepristone in the treatment of Cushing's syndrome is in its infancy. The cases
      reviewed in this report comprise the entire medical literature. Development and
      availability of mifepristone has been severely restricted because of controversy
      surrounding its ability to function as an "abortion pill." As the political
      controversy abates, increasing studies of this drug may be anticipated in
      patients with glucocorticoid excess. Although the authors have highlighted
      therapeutic trials with the drug, they also note that diagnostic uses in cases of
      glucocorticoid excess may be of interest. Some cases of endogenous Cushing's
      syndrome are difficult to diagnosis and a glucocorticoid antagonist may be as
      useful as a glucocorticoid agonist (such as dexamethasone) in the dynamic
      evaluation of glandular function. In particular, mifepristone might be useful in
      distinguishing pituitary from occult ectopic ACTH-secreting tumors. One of the
      primary problems surrounding the use of mifepristone in cases of Cushing's
      syndrome is the long half-life of the drug and the necessity to titrate doses
      carefully in a manner that avoids signs and symptoms of glucocorticoid
      deficiency. Biochemical markers reflecting the "glucocorticoid status" of a
      patient would be useful for dose adjustment and monitoring and would improve the
      risk to benefit ratio for mifepristone treatment of Cushing's syndrome.

PMID- 8734016
TI  - Use of a brief assessment examination in a study of subacute sclerosing
      panencephalitis.
AB  - Subacute sclerosing panencephalitis is a degenerative disease affecting children
      and young adults that remains a distinct and relatively frequent problem in
      developing countries worldwide. Recent advances in treatment prompted a study at
      King Faisal Specialist Hospital, Riyadh, Saudi Arabia, using oral isoprinosine
      and intraventricular alpha-interferon. Initially, the Neurological Disability
      Assessment and Index was used for tracking patient progress. However, an
      additional means of assessment was deemed necessary and the Brief Assessment
      Examination was devised. Largely cognitive based, the Brief Assessment
      Examination appeared to be more sensitive to mental status changes than the
      Neurological Disability Assessment and Index, though it correlated modestly with
      the Neurologic Disability Assessment and Index and more strongly with staging. In
      addition, the Brief Assessment Examination can be administered by technician
      level staff with a minimum of training. Though more study is needed, preliminary
      findings suggest that the Brief Assessment Examination should be a useful
      tracking tool for subacute sclerosing panencephalitis, particularly in the
      developing world.

PMID- 8734017
TI  - Vulnerability of the infant brain stem to ischemia: a possible cause of sudden
      infant death syndrome.
AB  - In infants, extreme extension or rotation of the head can occlude one or both
      vertebral arteries. We sought to determine whether small communicating arteries
      or asymmetric vertebral arteries could predispose the brain stem to ischemia
      should such head movements occur. In 68 infants, the carotid, posterior
      communicating, precommunicator posterior cerebral, basilar and vertebral arteries
      were fixed in formalin, embedded in resin, the circumferences measured by image
      analysis, and the relative conductance of blood in each artery per gram of brain
      calculated. Conductance in the vertebrobasilar and carotid systems lagged behind
      increases in brain weight during the postnatal growth spurt. In 81% of infants,
      conductance through the communicating arteries was less than 25% of basilar
      artery conductance. Conductance in one vertebral artery was less than half that
      of the contralateral artery in 41% of infants. In conclusion, the lag in
      available blood flow and small communicating and asymmetric vertebral arteries
      may predispose the infant brain stem to ischemia if one or both vertebral
      arteries are occluded by head rotation or extension. Because these head movements
      are likely to be accentuated in the prone sleeping position (a risk factor for
      sudden infant death syndrome), we suggest that vertebral artery occlusion may
      underlie some cases of sudden unexpected infant death.

PMID- 8734018
TI  - Familial dystonia and choreoathetosis in three generations associated with
      bilateral striatal necrosis.
AB  - Nine cases of dystonia and choreoathetosis (six females and three males) have
      developed in three generations of a single family. There has been one death.
      Neuropathologic examination disclosed bilateral striatal necrosis. In this
      family, the neurologic disorder has evolved gradually or in association with a
      febrile illness. There has been no neurologic recovery. The disease is worse in
      females, has been transmitted only through females, and shows incomplete
      penetrance and anticipation. The maternal inheritance pattern suggests either an
      autosomal dominant trait also affecting male reproductive ability or a defect
      involving the mitochondrial genome.

PMID- 8734019
TI  - Long-term outcome of fetal hydrocephaly.
AB  - Long-term outcome of 25 fetuses with ventriculomegaly diagnosed before delivery
      who survived the neonatal period up to school age was examined at 10.1 (standard
      deviation, 2.6) years of age. Twelve children had normal motor and mental
      development, seven were severely handicapped, and six showed intermediate
      outcome. The fetuses with severe handicaps on long-term follow-up had more severe
      ventricular dilation than the fetuses with good long-term outcomes. Eighteen of
      the children had surgical treatment, and seven of them had normal long-term
      development. Thirty percent of surviving fetuses with ventriculomegaly have poor
      long-term outcomes. In isolated progressive ventriculomegaly, early delivery as
      soon as fetal lung maturity allows might be reasonable for achievement of better
      long-term prognosis.

PMID- 8734020
TI  - Hypertensive encephalopathy in childhood.
AB  - Hypertensive encephalopathy is an uncommon but recognized complication of
      malignant hypertension in children. We reviewed the clinical course, laboratory
      studies, and outcomes of 12 patients with hypertensive encephalopathy seen at the
      University of Iowa Hospitals and Clinics between 1979 and 1994. The most common
      presenting symptoms were seizures, headache, and vision changes. Laboratory
      studies were nonspecific and in some patients were normal. Hypertensive
      encephalopathy is a clinical diagnosis. Management consists of recognition of
      this syndrome and aggressive treatment of hypertension. The neurologic outcome in
      our series was good.

PMID- 8734021
TI  - Study of subarachnoid spaces in children with idiopathic mental retardation.
AB  - The aim of this study was to assess quantitatively the size of the subarachnoid
      space in children with "idiopathic" mental retardation. The extent of various
      cerebrospinal fluid compartments was measured in 106 brain computed tomographic
      examinations of children with idiopathic mental retardation, and the results were
      compared with the corresponding normative data. The third ventricle was enlarged
      in 77% of the cases. A mild degree of diffuse widening of the subarachnoid spaces
      was found in about 30% of the patients. These morphologic alterations are
      additional observations supporting the hypothesis that "idiopathic" mental
      retardation has a biologic basis.

PMID- 8734022
TI  - Prognosis of childhood epilepsy in newly referred patients.
AB  - The aim of this study was to investigate the prognosis of childhood epilepsy and
      to analyze prognostic factors in addition to remission rate in a follow-up of
      newly referred patients. Two hundred eighty-one patients were followed for a mean
      period of 5.3 years. Overall, 253 patients (90%) achieved 1-year remission. The
      beginning of a 1-year seizure-free period was achieved in 77.9% by 1 year, in 84%
      by 2 years and in 88.6% by 3 years after onset of treatment. Early onset of
      seizures, symptomatic etiology, and neurologic handicap predicted a worse
      prognosis. In 44 of 253 children with complete suppression of seizures for 1
      year, relapses occurred within the follow-up period. In one child with a relapse,
      remission could not be achieved in the 2nd year thereafter. In conclusion, our
      study shows a good prognosis for most children with epilepsy, especially in
      patients with idiopathic epilepsy and late onset of seizures and without
      neurologic dysfunction. Moreover, our data strongly suggest that the long-term
      pattern of seizure control is largely established during the first 2 years of
      treatment.

PMID- 8734023
TI  - Blink reflex in cerebral palsy: evaluation of late components in patients with
      normal auditory brainstem responses.
AB  - The electrically elicited blink reflex was examined and evaluated quantitatively
      in 60 controls and seven patients with cerebral palsy due to perinatal asphyxia
      who exhibited normal auditory brainstem responses. In the controls, the early
      component (R1) latency changed slightly from infancy to adulthood, and the late
      component (R2 and R2') latencies decreased to adult values by 4 to 6 years of
      age. The electromyographic activity of R2 and R2' increased later and became
      mature in the young adolescent period. Prolonged R2 latency and decreased R2
      amplitude were observed more frequently than R1 abnormalities in the patients.
      The electromyographic activity of R2 in the patients was lower than that in
      control subjects more than 13 years old. Almost all patients showed bilateral
      cerebral atrophy and dilated lateral ventricles, but only one patient exhibited
      distinct pontine atrophy on cranial computed tomographic scan. These
      electrophysiologic abnormalities suggest that decreased excitability of
      interneurons of the reflex arc was present in the patients, particularly in older
      ones. The blink reflex test seems to be more sensitive than the auditory
      brainstem response for detecting brainstem dysfunction in patients with cerebral
      palsy due to neonatal asphyxia.

PMID- 8734024
TI  - Hypertrophy of temporalis muscles due to chewing gum "abuse".

PMID- 8734025
TI  - Evidence of a third locus for benign familial convulsions.
AB  - Two autosomal dominant forms of benign idiopathic epilepsy of early life have
      been described: benign neonatal familial convulsions and benign infantile
      familial convulsions. Herein we describe a pedigree with familial convulsions in
      which the age of onset is intermediate between that seen in these two disorders.
      Two genes responsible for benign neonatal familial convulsions have been mapped
      to chromosome 20q and to chromosome 8q. Previously, the chromosome 20q benign
      neonatal familial convulsions locus had been excluded in this pedigree. Further
      linkage analysis in our laboratory revealed that the chromosome 8 benign neonatal
      familial convulsions locus also is not responsible for seizures in this pedigree.
      These results indicate that there are at least three loci responsible for
      autosomal dominant benign epilepsies of early life.

PMID- 8734026
TI  - Severity of medical and neurologic complications as a determinant of
      neurodevelopmental outcome at 6 and 12 months in very low birth weight infants.
AB  - Very low birth weight (n = 154) and term infants (n = 119) had neurologic and
      developmental assessment at 6 and 12 months of age. Preterm infants with severe
      neonatal complications were considered to be at high risk, and those with milder
      complications were considered to be at low risk, for neurodevelopmental
      abnormality. Compared to term infants, high- and low-risk infants had
      abnormalities at 6 months in total neurologic score, cranial nerves, motor tone,
      motor coordination, and reflexes (P < .001). At 12 months, all groups had
      improved. However, high-risk infants had persistent abnormalities in the same
      subcategories (P < .001), whereas low-risk infants differed from term infants
      only in motor tone (P < .001). Bayley developmental scores were different for all
      groups at 6 months (P < .001), but at 12 months only high-risk infants differed
      from term infants (P < .01). These results demonstrate improvement in neurologic
      and developmental scores over time in very low birth weight infants. The degree
      of neurodevelopmental abnormality and improvement over time is related to
      severity of neonatal complications in preterm infants.

PMID- 8734027
TI  - Algorithms for the treatment of affective illness, primary disorder of vigilance,
      and task-dependent attention disorders (learning disabilities) in children and
      adolescents.

PMID- 8734028
TI  - Parkinsonian manifestations in a patient with homocystinuria.

PMID- 8734029
TI  - Childhood presentation of idiopathic epidural lipomatosis: a case report with
      magnetic resonance imaging and pathologic confirmation.

PMID- 8734030
TI  - Lissencephaly with pontocerebellar hypoplasia.

PMID- 8734031
TI  - Vitamin K-dependent coagulopathy in a child receiving anticonvulsant therapy.

PMID- 8734032
TI  - Hypertrophic intrafusal muscle fibers in infantile spinal muscular atrophy.

PMID- 8734033
TI  - The role of anticoagulation in idiopathic cerebral venous thrombosis.

PMID- 8734034
TI  - Neonatal cerebral arterial thrombosis: protein C deficiency.

PMID- 8734035
TI  - Congenital fumarase deficiency presenting with hypotonia and areflexia.

PMID- 8734036
TI  - The unmodulated oculocephalic reflex: clinical feature of the persistent
      vegetative state in the neonate.

PMID- 8734037
TI  - Cerebral malaria in children.

PMID- 8734038
TI  - The illness of Saint Fina.

PMID- 8734039
TI  - Different ways of looking at seeing.

PMID- 8734040
TI  - Anatomical substrates for early stages in cortical processing of visual
      information in the macaque monkey.

PMID- 8734041
TI  - On the specificity of neurons and visual areas.
AB  - The dominant view during the past 40 years has been that the visual system
      analyzes the visual scene by breaking it down into basic attributes such as
      color, form, motion, depth and texture. Individual dedicated neurons and specific
      visual areas were believed to be devoted to the analysis of each of these
      attributes. Current research has challenged these views by emphasizing that
      neurons, especially in the cortex, have multifunctional properties and therefore
      serve as general-purpose analyzers rather than feature detectors. Consequently,
      it appears that most extrastriate visual areas, rather than each being devoted to
      the analysis of a specific basic visual attribute, perform several different
      tasks and thereby engage in more advanced and complex analyses than had been
      realized.

PMID- 8734042
TI  - Interareal synchronization in the visual cortex.
AB  - The primary visual cortex (V1) is part of a highly interconnected network of
      cortical areas, hierarchically organized but operating concurrently across
      hierarchical levels. The high degree of reciprocal interconnection among visual
      cortical areas provides a framework for their interaction during the performance
      of visual scene analysis. The functional interdependency of visual cortical areas
      which develops during scene analysis can be investigated by techniques which
      measure interareal correlated activity. Evidence from monkeys performing a visual
      pattern discrimination suggests that synchronization of aperiodic activity from
      neuronal ensembles in cortical areas at different hierarchical levels is a
      relevant aspect of visual function. The near-periodic nature of the synchronized
      response to moving light bars in earlier studies may have been a result of the
      type of stimulus used. Various models of visual cortex are discussed in which
      interareal synchronization plays a functional role.

PMID- 8734043
TI  - Neuronal mechanisms of color categorization in areas V1, V2 and V4 of macaque
      monkey visual cortex.
AB  - A landmark study conducted by Berlin and Kay (Basic Color Terms, University of
      California Press, Berkeley, 1969, pp. 1-12) demonstrates that well-developed
      languages contain exactly 11 basic color terms. The basic colors (8 chromatic and
      3 achromatic) are situated in specific locations of color space, suggesting a
      fixed relationship between specific hue and luminance. To determine the
      physiologic origins of the basic colors, we have studied the responses of cells
      in visual cortical areas V1, V2 and V4 of the behaving macaque monkey, using
      chromatic and achromatic stimuli of varying luminance. A total of 569 cells (291
      from V1, 205 from V2, 73 from V4) were obtained, and classified as 'B' (bright;
      43-50% of the total cells in each area), 'D' (dark; 6-12% of the total), and
      'B/D' (bright/dark; 27-28% of the total) color or non-color cells according to
      each cell's color/luminance preference in relation to the neutral gray
      background. About two thirds of 'B' cells in each area were color specific,
      whereas the proportion of color cells in 'B/D' and 'D' categories was lower. In
      all three areas (v1, V2, V4), color cells with preferences for midspectral colors
      (such as yellow, lime and green) also preferred high luminance levels, while
      color cells with preferences for endspectral colors (such as red and blue)
      responded preferentially to luminance levels closer to background. The date
      provide evidence for categorical color perception within the visual system, as
      well as providing a physiological basis for the increased saliency of endspectral
      contours observed at equiluminance in psychophysical studies.

PMID- 8734044
TI  - Color, orientation and cytochrome oxidase reactivity in areas V1, V2 and V4 of
      macaque monkey visual cortex.
AB  - Color and orientation processing in the macaque monkey first segregates into
      cytochrome oxidase (CO)-rich blobs and -poor interblobs of area V1, from where
      the two streams flow through areas V2 and V4. This parallel representation is
      believed to enhance processing speed by compartmentalizing tasks of similar
      kinds, though our knowledge of the mechanisms is still elementary. We have
      examined the interaction and separation of color and orientation processing in
      neurons (n = 569) of the macaque visual cortex (V1, V2, V4) on the basis of
      microelectrode recordings. In all three areas, neurons selective for midspectral
      (MS) colors (e.g., yellow, green) were also found to be more orientation
      selective than those preferring endspectral (ES) colors (e.g., blue, red). The
      majority of achromatic (AC) cells responsive to bright stimuli were also
      orientation selective. When locations of cells and penetration columns were
      correlated with cytochrome oxidase (CO) landmarks in V1 and V2, V1 interblob and
      V2 interstripe cells were found to be predominantly midspectral and oriented,
      while V1 blob and V2 thin stripe cells were found to be predominantly endspectral
      and non-oriented. Cells preferring dark colors were found to cluster in thick
      stripes in V2, and in columns in V4. Separate clustering of midspectral (MS) and
      endspectral (ES) systems in V4 was also noted. With the results shown in a
      companion paper (Behav. Brain Res., 76 (1996) 51-70), the present data indicate
      that the visual system appears to optimize color and spatial acuity by separating
      chromatic information into non-oriented endspectral and oriented midspectral
      components.

PMID- 8734045
TI  - Functional streams in occipito-frontal connections in the monkey.
AB  - It is known that the prestriate cortical regions that project to area LIP in
      parietal cortex and to areas TEO and TE in temporal cortex are mostly separated.
      Two separate streams of information transfer from occipital cortex can this be
      distinguished. We wished to determine whether the parietal and temporal streams
      remain segregated in their projections to frontal cortex. Paired injections of
      retrograde fluorescent tracers were placed in parietal and temporal cortex, or in
      the lateral and medial parts of the frontal eye field (FEF). The cortical regions
      containing retrogradely labeled cells were reconstructed in two-dimensional maps.
      The results show that temporal cortex mainly projects to lateral FEF (area 45).
      Parietal cortex sends projections to medial FEF (area 8a) and to lateral FEF, as
      well as to area 46. Thus, the parietal and temporal streams converge in lateral
      FEF. Most of the occipital regions projecting to medial FEF are the same as those
      projecting to parietal cortex, whereas lateral FEF receives afferents from the
      same occipital regions as those sending projections to temporal cortex. Thus, one
      can distinguish two interconnected networks. One is associated with the
      inferotemporal cortex and includes areas of the ventral bank and fundus of the
      superior temporal sulcus (STS), lateral FEF and ventral prestriate cortex. This
      network emphasizes central vision, small accades and form recognition. The other
      network is linked to cortex of the intraparietal sulcus. It consists of areas of
      the upper bank and fundus of STS, medial FEF and dorsal prestriate cortex. These
      areas encode peripheral visual field and are active during large saccades.

PMID- 8734046
TI  - The representation of shape in the temporal lobe.

PMID- 8734047
TI  - A neurological dissociation between shape from shading and shape from edges.
AB  - We studied the ability of a neurological patient, who has deficits in various
      aspects of form perception, to perform region segregation tasks requiring
      discriminations based on several image properties that are related to the three
      dimensional structure of objects. The patient could discriminate the apparent
      three-dimensional structure and orientation of shapes defined by shading
      gradients, but could not make such discriminations for shapes in which edges were
      depicted as lines or as luminance discontinuities. These results suggest that the
      neural pathways that compute shape from shading gradients may be independent of
      those that compute shape based on edges, and, based on the patient's pattern of
      brain damage, they also indicate a relatively early functional separation in the
      requisite inputs.

PMID- 8734048
TI  - The effects of visual cortex lesions on the perception of rotated shapes.
AB  - Monkeys with inferior temporal cortex lesions cannot discriminate between
      different shapes (e.g., + vs. O) but can discriminate between shapes that differ
      only in orientation (e.g., 6 vs 9). Lesions of the parietal cortex, on the other
      hand, impair the discrimination of rotated shapes but spare the ability to
      discriminate between different shapes. A similar dissociation is found between
      some visual agnosics who can match but not identify rotated views of objects and
      other patients who can identify and discriminate objects only if the view is
      conventional; any change in orientation disrupts performance. In this paper we
      argue that two mechanisms may be available for the perception of rotated shapes.
      Which mechanism is used depends on the degree of rotation. It is suggested that
      the different effects of parietal and temporal lesions reflect the relative
      contributions of the two areas to the task and disrupt different stages of the
      two strategies used. A framework for the cortical processing of rotated shapes in
      the non-human primate is presented.

PMID- 8734049
TI  - Cortical mechanisms for visual perception of object motion and position in space.
AB  - The present review is aimed at analyzing and discussing some of the cortical
      mechanisms possibly involved in the perception of object motion and object
      localization in the visual field. A comprehensive approach to these topics would
      be beyond the scope of this work. The highest priority, therefore, will be given
      to the cortical machinery involved in these processes, while very little (or
      nothing at all) will be said on the possible role played by subcortical
      structures such as the lateral geniculate nucleus and the superior colliculus
      which, albeit not directly involved in perception, might contribute to it.

PMID- 8734050
TI  - Motion sensitive cells in the macaque superior temporal polysensory area:
      response discrimination between self-generated and externally generated pattern
      motion.
AB  - It was previously shown [17] that visual movement sensitive neurons lacking
      selectivity in the anterior parts of the dorsal superior temporal sulcus (STP) of
      monkeys exhibited selective responses to externally moved objects and failed to
      respond to the sight of the animal's own limb movements. This paper describes a
      series of experiments in which a monkey was trained to operate an apparatus that
      produced visual motion of a projected two-dimensional patterned stimulus. Single
      unit responses from STP were recorded and responses to visual motion, produced
      externally by the experimenter, were compared to the responses to visual motion
      (of the same pattern) produced by the monkey itself. The majority of the movement
      sensitive cells giving reliable responses to the pattern motion responded
      statistically more strongly to the experimenter-induced motion than to the motion
      induced by the monkey itself. The cell responses were observed not to be affected
      by the motion velocity and the monkey's motor activity (handle rotation without
      any visual stimulation) did not affect the cell's spontaneous activity. The
      results indicate that the response discrimination of STP cells between externally
      and self-induced stimulus motion is not based on form sensitivity. Moreover, the
      mechanism which produces the described response selectivity is not only limited
      to naturally occurring visual consequences of the monkey's own motor activity but
      is plastic and can extend to arbitrary associations between the monkey's
      movements and consequent visual motion.

PMID- 8734051
TI  - Perception of motion-in-depth in patients with partial or complete cerebral
      hemispherectomy.
AB  - Four patients with functional hemispherectomy, one patient with a complete
      anatomical hemispherectomy, and one patient with unilateral removal of the
      temporal, parietal and occipital lobes took part in two sets of experiments
      designed to investigate their residual sensitivity to motion-in-depth in the
      hemianopic visual field. Two types of computer-generated visual displays were
      used; in the first set of experiments, a dot pattern and in the second, a
      circular checkerboard. These simulated either convergent, divergent or reversed
      rotational motion. Each set of experiments consisted of two parts; in the first
      part, electrodermal responses were monitored during stimulus presentation while
      the subjects performed a simple distracting task. In the second part, subjects
      were asked to state verbally the direction of stimulus motion. Contrary to
      expectations, no reliable changes in skin conductance were elicited from any of
      the subjects by changes in the direction of motion of the component parts of
      either the dot pattern display or the circular checkerboard display. Furthermore,
      none of the subjects were able to discriminate the direction of motion of the
      target patterns when presented in the hemianopic field. The most parsimonious
      explanation is that the subcortical visual pathways which survive hemispherectomy
      are unable to process visual information relating to motion in depth.

PMID- 8734052
TI  - Is face recognition 'special'? Evidence from neuropsychology.
AB  - Is face recognition 'special,' in the sense of relying on functionally and
      anatomically distinct mechanisms from those required for other kinds of pattern
      recognition? A number of different neuropsychological dissociations involving
      recognition and learning of faces and nonface objects are reviewed. In addition,
      studies of the nature of shape representation in normal face and object
      recognition are reviewed. The evidence from brain-damaged and normal subjects
      suggests that face recognition is, indeed, 'special,' and provides some clues to
      the functional differences between face and object recognition.

PMID- 8734053
TI  - Stimulus specific adaptation in inferior temporal and medial temporal cortex of
      the monkey.

PMID- 8734054
TI  - Perception, learning and identification studied with reversible suppression of
      cortical visual areas in monkeys.
AB  - We use cold to reversibly suppress cortical areas involved in visual perception,
      learning and retrieval and we found a localization of functions essential for
      performance of delayed match-to-sample (DMS) in anterior ventral temporal cortex,
      we call ventral TE (TEv). We also found a visual input for this area that is
      separate from the one going to the heart of inferotemporal cortex and suppressing
      this input also impairs performance of DMS. Suppressing the dorsal half of TE
      (TEd) disrupts retrieval of some, but not all complex images, and different
      images are disrupted in different animals. This variability within and between
      animals is extreme, with perfect performance on some complex images and below
      chance on others. We suggested that TEd represents some, but not all elements of
      the images. In attempting to discover what those elements might be, we found that
      TEd suppression disrupts the perception of small figures, but not the larger
      figures that they compose. We also found that it impaired the discrimination and
      matching of colors, without impairing the ability to detect and differentiate
      hues. We proposed that TEd represents the details and colors of things, but not
      global figures. Also, complex objects do not have a representation in one area,
      rather its representation involves the entire visual system, including TE with
      different elements of the image represented in different parts.

PMID- 8734055
TI  - Task dependency of visual processing in the human visual system.
AB  - In this review we contrast passive, attribute driven processing in the visual
      system with an active, task-dependent view and summarize the evidence from our
      Positron Emission Tomography (PET) work supporting the task-dependent view. The
      PET studies involved comparison of regional Cerebral Blood Flow (rCBF) in closely
      related detection and discrimination tasks. The major finding reported is that
      the same retinal input or input containing only a single cue activates different
      extrastriate areas depending on the task.

PMID- 8734056
TI  - An interpretation of 14C-urea and 14C-primidone extraction in isolated rabbit
      lungs.
AB  - We measured the venous concentration versus time curves of 14C-urea and 14C
      primidone after rapid bolus injections of a vascular reference indicator,
      fluorescein isothiocyanate dextran, and one of the two 14C-labeled indicators in
      isolated rabbit lungs perfused with Krebs-Ringer bicarbonate solution containing
      4.5% bovine serum albumin at flow rates (F) of 6.67, 3.33, 1.67, and 0.83 ml/sec
      and with nearly constant microvascular pressure and total lung vascular volume.
      When we calculated the permeability-surface area product, PS, from the 14C-urea
      and 14C-primidone outflow curves using the Crone model, the estimates of the PS
      product were directly proportional to F. However, the fractional change in the PS
      with flow was different for the two indicators. We also estimated the PS from the
      same 14C-urea and 14C-primidone data using an alternative model that includes
      perfusion heterogeneity, estimated in a previous study, and flow-limited and
      barrier-limited extravascular volumes accessible to both urea and primidone. This
      model was able to fit the outflow curves of either 14C-urea or 14C-primidone at
      all four flows studied with one flow-independent PS for each indicator. The
      ability of the new model to explain the 14C-urea and 14C-primidone data with no
      flow-dependent change in PS suggests that a change in PS with F estimated using
      other models such as the Crone model is not sufficient for capillary surface area
      recruitment.

PMID- 8734057
TI  - Modeling blood flow heterogeneity.
AB  - It has been known for some time that regional blood flows within an organ are not
      uniform. Useful measures of heterogeneity of regional blood flows are the
      standard deviation and coefficient of variation or relative dispersion of the
      probability density function (PDF) of regional flows obtained from the regional
      concentrations of tracers that are deposited in proportion to blood flow. When a
      mathematical model is used to analyze dilution curves after tracer solute
      administration, for many solutes it is important to account for flow
      heterogeneity and the wide range of transit times through multiple pathways in
      parallel. Failure to do so leads to bias in the estimates of volumes of
      distribution and membrane conductances. Since in practice the number of paths
      used should be relatively small, the analysis is sensitive to the choice of the
      individual elements used to approximate the distribution of flows or transit
      times. Presented here is a method for modeling heterogeneous flow through an
      organ using a scheme that covers both the high flow and long transit time
      extremes of the flow distribution. With this method, numerical experiments are
      performed to determine the errors made in estimating parameters when flow
      heterogeneity is ignored, in both the absence and presence of noise. The
      magnitude of the errors in the estimates depends upon the system parameters, the
      amount of flow heterogeneity present, and whether the shape of the input function
      is known. In some cases, some parameters may be estimated to within 10% when
      heterogeneity is ignored (homogeneous model), but errors of 15-20% may result,
      even when the level of heterogeneity is modest. In repeated trials in the
      presence of 5% noise, the mean of the estimates was always closer to the true
      value with the heterogeneous model than when heterogeneity was ignored, but the
      distributions of the estimates from the homogeneous and heterogeneous models
      overlapped for some parameters when outflow dilution curves were analyzed. The
      separation between the distributions was further reduced when tissue content
      curves were analyzed. It is concluded that multipath models accounting for flow
      heterogeneity are a vehicle for assessing the effects of flow heterogeneity under
      the conditions applicable to specific laboratory protocols, that efforts should
      be made to assess the actual level of flow heterogeneity in the organ being
      studied, and that the errors in parameter estimates are generally smaller when
      the input function is known rather than estimated by deconvolution.

PMID- 8734058
TI  - Determination of specific oxygen uptake rates in human hematopoietic cultures and
      implications for bioreactor design.
AB  - Oxygen plays an important role in the cultivation of primary cells ex vivo. In
      this study, we used hermetically sealed tissue culture well inserts equipped with
      oxygen electrodes to measure the oxygen utilization of cultured human bone marrow
      mononuclear cells (BM MNCs). The oxygen uptake rate (OUR) of BM MNCs was
      determined during a 14-day culture in which both adherent and nonadherent cells
      were present. Early in the culture, the cells exhibited very low OURs. The
      specific OURs (uptake rate per cell) were at approximately 0.005 mumol/10(6)
      cells/hr shortly after the initiation of culture. The OUR then increased as the
      cultures developed. After about 8 to 10 days of cultivation the specific OURs had
      increased to 0.038 +/- 0.006 and 0.025 +/- 0.005 mumol/10(6) cells/hr for
      adherent and nonadherent cells, respectively, after which no further increase was
      observed. Based on these oxygen uptake rate data, a mathematical model of oxygen
      diffusion was formulated and use to investigate issues associated with
      hematopoietic bioreactor design, including initial cell density, medium depth,
      reactor configuration, and oxygen partial pressure. In situ OUR measurements
      confirmed predicted oxygen limitations based on the mathematical model and the
      experimentally determined OURs. High-density hematopoietic cultures present
      design challenges in terms of sufficient and uniform delivery of oxygen to an
      active hematopoietic culture. These challenges can be met by using parallel-plate
      bioreactors with thin liquid layers.

PMID- 8734059
TI  - Hemodynamic modulation of monocytic cell adherence to vascular endothelium.
AB  - Hemodynamic shear stress is hypothesized to contribute to the localization of
      atherosclerotic plaques to certain arterial sites. Monocyte recruitment to these
      sites is an early event in artherogenesis. To determine the possible mechanisms
      by which shear stress modulates monocyte adhesion in vivo, studies of human
      monocytic cell adherence to endothelium were conducted under different shear
      conditions in a parallel-plate flow chamber. The number of monocytes capable of
      developing firm adhesive contacts with endothelium decreased as shear stress
      induced drag forces increased over the range of 0.5 to 30 dynes/cm2. The number
      of adherent monocytic cells at a given shear stress was highly dependent on the
      activation state of the endothelium. To test the direct effect of shear stress on
      endothelial cell adhesivity, endothelial cells were presheared for 2 to 6 hr at
      2, 10, or 30 dynes/cm2, and monocytic cell adherence was quantified at 1
      dyne/cm2. Adherence increased 330% or 370% when endothelial cells were presheared
      for 2 hr at 2 or 10 dynes/cm2, respectively, as compared to unsheared
      endothelium. In contrast, when endothelial cells were presheared at 30 dynes/cm2,
      monocytic cell adherence at 1 dyne/cm2 was not significantly different from
      unsheared controls. Increased monocytic cell adherence to presheared endothelium
      was via a vascular cell adhesion molecule 1 (VCAM-1)/alpha(4) beta(1) mechanism,
      and enzyme-linked immunosorbent assay studies showed that preshearing at 2
      dynes/cm2 for 2 hr increased endothelial VCAM-1 expression by 38%. These data
      demonstrate that low levels of shear stress induce endothelial VCAM-1 expression
      and increase monocytic cell adherence via a VCAM-1/alpha 4 beta 1 mechanism.
      Thus, shear stress can modulate monocyte adherence to vascular endothelium
      through drag forces that affect the establishment and maintenance of adhesive
      bonds and by directly modulating the expression of endothelial VCAM-1. This dual
      effect of shear stress produces the most favorable conditions for adhesion at low
      shear regions, where drag forces are low and induction of VCAM-1 is likely. The
      preferential adherence of monocytes to these regions may contribute to the
      localization of atherosclerotic plaques to low-shear regions of the arterial
      circulation in vivo.

PMID- 8734060
TI  - A numerical analysis of factor X activation in the presence of tissue factor-
      factor VIIa complex in a flow reactor.
AB  - A mathematical model has been developed to investigate previously obtained
      experimental findings relating to the activation of factor X by surface-bound
      tissue factor--factor VIIa (TF:VIIa) in a tubular flow reactor. In those
      experiments, factor X was perfused through a microcapillary tube over a range of
      flow (shear) conditions and the activated product, factor Xa, was measured at the
      outlet of the tube using a chromogenic assay. In the present study, the steady
      state convection-diffusion equation with Michaelis-Menten kinetics used to
      describe the reaction at the wall was numerically integrated using an implicit
      method based on linear systems of ordinary differential equations. The results
      from the numerical analysis indicated that shear rate directly affects both Km
      and Vmax. Values of Km decreased from 151 to 16 nM as the shear rate increased
      from 25 to 2400 sec-1. Additionally, there was a twofold increase in Vmax from
      1.4 to 3.0 pmol/cm2/min as the shear rate increased from 25 to 300 sec-1. These
      findings are in contrast with classical enzyme behavior and imply a direct effect
      of fluid flow on the kinetics of factor X activation.

PMID- 8734061
TI  - Tensions and stresses of ellipsoidal chambers.
AB  - Equations for calculating wall tensions in an ellipsoidal chamber might be useful
      in analyses of elongated chambers whose transverse sections are not round, and
      they should be useful for examining the tension distribution associated with such
      shapes. Considering the forces changing a prolate spheroid (semiaxes a > b = c)
      into a general ellipsoid (semiaxes a > b > c) led to an equation for tensions at
      the poles of an ellipsoid. Considering the thickness distribution of a chamber of
      uniform average stress led to an equation for the average of orthogonal tensions
      at any point on an ellipsoidal chamber. Applying these equations with Laplace's
      law to points along an axis plane showed that tension normal to that plane is a
      weighted average of tensions normal to that plane at the intersections of the
      ellipsoid with the other two axis planes. It was postulated that this rule also
      would apply to the tension component normal to a plane coincident with any hoop
      (line of constant distance from one axis plane), and this postulate led to an
      equation for tension orthogonal to a hoop at any point. These three equations
      (pole tensions, local average tension, local hoop-orthogonal tension) allowed
      calculation of the tension tensor at any point. The equations and their algorithm
      were validated by four tests: the surface integral of the average of orthogonal
      tensions is as necessary for tensile work to equal hydraulic work in a
      symmetrical displacement (satisfying chamber equilibrium), the line integral of
      the component of tension normal to any hoop-coincident plane is equal to the
      product of pressure and area in the hoop (satisfying force balance), at any point
      the tensions predicted from the tensor for the directions of greatest and least
      curvature are compatible with Laplace's law (satisfying local equilibrium), and
      the calculated principal-tension lines relate properly to the nodes where tension
      is the same in all surface directions. These tests could be used to validate
      finite-element analyses of complex chambers.

PMID- 8734062
TI  - Role of proximal electrode position in transvenous ventricular defibrillation.
AB  - Transvenous defibrillation lead systems have been demonstrated to reduce
      operative morbidity and mortality associated with implantation of cardioverter
      defibrillators. To determine the best position for the proximal electrode in
      transvenous systems, defibrillation thresholds were compared for three positions
      in a single-pathway, two-lead system. Two defibrillation lead electrodes were
      transvenously inserted into seven dogs. The distal electrode was positioned in
      the right ventricular apex. The proximal electrode was randomized to one of three
      positions: (1) the superior (cranial) vena cava (SVC) at the junction of the
      right atrium, (2) the left innominate vein at the junction of the SVC, or (3) the
      external jugular vein. Biphasic defibrillation thresholds for converting
      electrically induced ventricular fibrillation were determined for the three
      positions of the proximal electrode in each dog. The innominate vein position
      resulted in the lowest defibrillation threshold (555 +/- 123 V) as compared to
      the SVC (640 +/- 126 V; p = 0.0612) and the jugular vein (709 +/- 117 V; p =
      0.0013). Lead impedance gradually increased with increasing distance between the
      two shocking electrodes: 58.4 +/- 11.4 omega for SVC, 76.2 +/- 13.8 omega for
      innominate vein, and 94.9 +/- 10.2 omega for jugular vein proximal lead electrode
      position (p < 0.05 for all pairwise comparisons). In two-electrode transvenous
      defibrillation lead systems, positioning the proximal electrode in the left
      innominate vein produced the lowest defibrillation threshold.

PMID- 8734063
TI  - Electroencephalographic changes following low energy emission therapy.
AB  - Low energy emission therapy (LEET) is a novel approach to delivering low levels
      of amplitude-modulated electromagnetic fields to the human brain. The sleep
      electroencephalogram (EEG) effects of a 15-min LEET treatment were investigated
      in a double-find cross-over study to assess sleep induction. Fifty-two healthy
      volunteers were exposed to both active and inactive LEET treatment sessions, with
      a minimum interval of 1 week between the two sessions. Baseline EEGs were
      obtained, and 15-min posttreatment EEGs were recorded and analyzed according to
      the Loomis classification. A significant increase in the duration of stage B1
      sleep (0.58 +/- 2.42 min [mean +/- SD], p = 0.046), decreased latency to the
      first 10 sec epoch of sleep (-1.23 +/- 5.32 min, p = 0.051) and decreased latency
      to sleep stage B2 (-1.21 +/- 5.25 min, p = 0.052) were observed after active
      treatment. Additionally, establishment of slow waves with progression from stages
      B to C was significantly more pronounced after active LEET treatment (p = 0.040).
      A combined analysis of these results with those of an identical study performed
      in Denver showed that LEET had a significant effect on afternoon sleep induction
      and maintenance with shorter sleep latencies (decreased latency to the first 10
      sec epoch of sleep; -1.00 +/- 5.51 min, p = 0.033; decreased latency to sleep
      stage B2; -1.49 +/- 5.40 min, p = 0.003), an increased duration of stage B2 (0.67
      +/- 2.50 min, p = 0.003), an increase in the total duration of sleep (0.69 +/-
      4.21 min, p = 0.049), and a more prominent establishment of slow waves with
      progression to a deeper sleep stage (p = 0.006). It is concluded that the
      intermittent 42.7 HZ amplitude modulation of 27.12-MHz electromagnetic fields
      results in EEG changes consistent with shorter sleep latencies, longer sleep
      duration, and deeper sleep in healthy subjects.

PMID- 8734064
TI  - Multimodality multidimensional image analysis of cortical and subcortical
      plasticity in the rat brain.
AB  - In this work, we developed and implemented a multimodality multidimensional
      imaging system which is capable of generating and displaying anatomical and
      functional images of selected structures and processes within a vertebrate's
      central nervous system (CNS). The functional images are generated from [14C]-2
      deoxy-D-glucose (2DG) autoradiography whereas the anatomic images are derived
      from cytochrome oxidase (CO) histochemistry. This multi-modality imaging system
      has been used to study mechanisms underlying information processing in the rat
      brain. We have applied this technique to visualize and measure the plasticity
      (deformation) observed in the rat's whisker system due to neonatal lesioning of
      selected peripheral sensory organs. Application of this imaging system revealed
      detailed information about the shape, size, and directionality of selected
      cortical and subcortical structures. Previous 2-D imaging techniques were unable
      to deliver such holistic information. Another important issue addressed in this
      work is related to image registration problems. We developed an image
      registration technique which employs extrinsic fiduciary marks for alignment and
      is capable of registering images with subpixel accuracy. It uses the information
      from all available fiduciary marks to promote alignment of the sections and to
      avoid propagation of errors across a serial data set.

PMID- 8734065
TI  - Nonlinear feedback models for the tuning of auditory nerve fibers.
AB  - The tuning of auditory nerve (AN) fibers is generally characterized by an
      increase in bandwidth and, for mid- to high-frequency fibers, a downward shift in
      the center frequency as sound level increases. Changes in bandwidth are
      accompanied by changes in the phase properties of the fibers; thus the timing of
      neural discharges also changes as a function of sound level. This study focuses
      on the magnitude and phase properties of models designed to reproduce the
      nonlinear properties of AN fibers that were studied electrophysiologically. The
      forward path of each model consisted of a linear second-order resonance, and each
      feedback path contained a saturating nonlinearity. In model 1, the feedback path
      was a simple memoryless, saturating nonlinearity. In model 2, a low-pass filter
      was added after the feedback nonlinearity. The ability of each model to simulate
      aspects of the nonlinear tuning of AN fibers is discussed. Model 2 was able to
      simulate a wider range of nonlinear behavior for different AN fibers and thus has
      promise for use in simulations of populations of fibers tuned to different
      frequencies.

PMID- 8734066
TI  - The twisting of the heart during contraction.

PMID- 8734067
TI  - Development of a skin model based on insoluble fibrillar collagen.
AB  - A biocompatible, 3-dimensional, noncontracting, crosslinked collagen matrix was
      adapted to promote differentiation of epidermal keratinocytes. To produce the
      matrix, a 3% wt/wt dispersion of insoluble bovine collagen containing 5 mg
      polylysine/g collagen in 0.001 N HCl was blended, lyophilized, and crosslinked
      using a dehydrothermal technique. Matrices 4 cm2 and 3 mm thick were seeded with
      human dermal fibroblasts (1 x 10(5)/cm2). After 5 days in culture, the matrices
      were seeded with human epidermal keratinocytes (1 x 10(5)/cm2). The cultures were
      grown submerged for 1 week and raised to the liquid/air interface for 3 weeks to
      promote epidermal differentiation. Based on morphology and immunological staining
      with antibodies for human involucrin, keratin 1 (k1), filaggrin, and loricrin,
      the state of differentiation of the epidermal layer was nearly equivalent to that
      seen with cultures grown on contracted collagen lattices produced according to
      the methodology described in the literature and similar to the pattern produced
      in normal neonatal foreskin. These results demonstrate the usefulness of an in
      vitro skin model employing a crosslinked collagen matrix that permits the
      incorporation of additional covalently linked bioactive molecules during matrix
      formation.

PMID- 8734068
TI  - Metacarpal fracture fixation with absorbable polyglycolide rods and stainless
      steel K wires: a biomechanical comparison.
AB  - Self-reinforced polyglycolide (SR-PGA) rods have been used widely for fracture
      fixation as an alternative to metallic implants. However, because of its
      insufficient strength and strength retention, the use of SR-PGA has been
      restricted to fractures or osteotomies of low stress bearing cancellous bone. To
      investigate its usefulness in fixing the fractures of cortical bone, the
      mechanical strength of a human metacarpal fracture fixed with SR-PGA rods was
      evaluated. The surgical constructs were immersed in buffered saline solution and
      maintained at body temperature (37 degrees C). The mean initial bending stiffness
      of the specimens fixed with the SR-PGA rods was 61% of that of the specimens
      fixed with Kirschner wires. The bending stiffness of the specimens fixed with the
      SR-PGA rods decreased gradually, and most of the specimens lost their mechanical
      stability when immersed for 4 weeks. When SR-PGA rods are used to fix the
      fracture of human cortical bone, such as diaphyseal fracture of the metacarpal
      bone, it should be protected by additional means.

PMID- 8734069
TI  - Fracture toughness of bone using a compact sandwich specimen: effects of sampling
      sites and crack orientations.
AB  - The energy required to propagate a crack through bone can be estimated in terms
      of its fracture toughness, which is an intrinsic property and an important
      measure of the material's susceptibility to fracture. However, in the past
      detailed fracture toughness characterization of bone has been limited due to
      specimen size limitations. To address this issue the present study used a compact
      sandwich specimen and examined the variation in fracture toughness of bovine
      femoral bone as a function of testing sites and crack orientations. Two crack
      orientations, radial and circumferential, and three testing sites situated along
      the thickness of bone were investigated. The results indicated that there were
      statistically significant differences in fracture toughness between the testing
      sites for both radial and circumferencial cracks. Crack orientation also appeared
      to influence the fracture toughness at two of the test sites. The microstructure
      of bone and its fracture surface morphology were examined using microscopy and
      exhibited differences corresponding to the differences in fracture toughness,
      thus suggesting a correlation between microstructure and fracture toughness.

PMID- 8734070
TI  - A two-step embedding process for better preservation of soft tissue surrounding
      coral implants.
AB  - Infiltration of paraffin or embedding polymers proceeds more quickly in soft than
      in mineralized tissue specimens (bone or biomaterial). The proposed method takes
      advantage of this difference to protect soft tissue from the action of
      decalcifying agents. After embedding a bone-soft-tissue sample in a hydrophobic
      polymer, it is cleared of the resin on one of its sides to permit access of the
      decalcifying solution to the mineral component. A second infiltration with
      another polymerizable solution that cures in the empty pores created by the
      dissolution makes it possible to obtain a homogeneous hard block, make thin
      slices, and perform enzyme histochemistry and immunostaining on well-preserved
      soft tissue with most of its antigenic and enzymatic properties intact.

PMID- 8734071
TI  - Evaluation of slipperiness of catheter surfaces.
AB  - A test method is described that allows the characterization of the subjective
      feeling of lubricity of catheter surfaces in a quantitative way. The test
      consists in pulling out, by a weight, a catheter tubing from a test tube filled
      with agar. Results show that the surface of a polyurethane catheter tubing coated
      with the hydrophilic poly (hydroxyethylmethacrylate) is readily hydrated by the
      water contained in the agar. The hydrogel coated tubing slides very quickly, due
      to the lubricating surface layer of water. The untreated polyurethane tubing and
      the same tubing after plasma treatment were definitely less slippery than the
      poly (hydroxyethylmethacrylate) coated ones. Atomic force microscopy was used to
      evaluate the contribution of the surface morphology of the samples to the
      obtained results.

PMID- 8734072
TI  - Collagen-based devices for soft tissue repair.
AB  - The intrinsic biological and physiochemical characteristics of collagen have been
      exploited to prepare a variety of commercially available medical products
      spanning many medical specialties. The properties of purified collagen can be
      modified to obtain forms which comply to specific applications. In particular,
      collagen materials in the form of gels, matrices, and films have been applied,
      either alone or in combination with other agents, to address soft tissue repair.
      This review describes how the versatile properties of collagen have made it one
      of the most useful biomaterials for wound care applications.

PMID- 8734073
TI  - Needle puncture resistance of surgical gloves, finger guards, and glove liners.
AB  - New puncture resistant materials are being developed for health professional use
      as protection against disease and needle stick injuries. The needle puncture
      resistance of protective gloves and glove liners from DePuy DuPont Orthopaedics
      and of finger guards from Zimmer was evaluated using a computerized needle
      penetration system to determine maximal penetration forces and the penetration
      work required for taper point and for cutting edge needles to penetrate these
      membranes. The Medak portion of the Life Liner glove liner and the Spectra
      portion of the FingGuard finger guard offered remarkable resistance against
      needle penetration as compared to the other glove liners and gloves tested. The
      cutting edge needles required considerably less penetration force and work to
      penetrate the FingGuard and Life Liner than that required with comparable size
      taper point needles. Because these unique protective materials had a limited
      distribution over the hand, the surgeon's hand remained susceptible to
      inadvertent needle puncture. While this protection against needle penetration in
      the Life Liner and the FingGuard represents an exciting advance in surgery, it is
      important to emphasize that this development is only one consideration in the
      selection of surgical gloves.

PMID- 8734074
TI  - Effect of puncture resistant surgical gloves, finger guards, and glove liners on
      cutaneous sensibility and surgical psychomotor skills.
AB  - New puncture and cut resistant hand protection systems have been developed to
      enhance the barrier to cuts and needle puncture injuries during surgical
      procedures. It is important, however, that these new hand protection systems do
      not reduce tactile sensitivity or dexterity during surgery. Consequently, it was
      the purpose of this report to compare the cutaneous sensibility and dexterity of
      physicians' hands covered by these new puncture and cut resistant hand protection
      systems to that of the standard surgical latex glove. The hide (Medak) portion of
      the Life Liner and the polyethylene (Spectra) portion of the FingGuard, which
      offered the greatest resistance to needle puncture, were associated with the
      greatest reduction in cutaneous sensibility, as determined by moving and static
      two-point discrimination, aesthesiometer pressure sensation, and discrimination
      of suture size and configuration. In addition, the physicians believed that the
      puncture and cut resistant Life Liner glove liner markedly interfered with their
      handling of surgical instruments. The ultimate benefit of these puncture and cut
      resistant hand protection systems must be determined in well-controlled clinical
      trials.

PMID- 8734075
TI  - Biomaterials crisis in the medical device industry: is litigation the only cause?

PMID- 8734076
TI  - [Course of ischemic risk in treated atheromatous hypertensive patients. The
      PRIHAM study].
AB  - Hypertension is one of the major cardiovascular risk factors. However seldom
      occurs alone in a patient and the antihypertensive treatment should be taken into
      account when assessing global cardiovascular status. The PRIHAM study was an open
      study which enrolled 3,216 hypertensive atheromatous patients who already has had
      a clinical ischaemic accident. Patients were followed-up for 3 years. The
      lowering effect on cardiovascular risk, starting from the fifteenth month was
      confirmed to the end of 36-month study. The effect on blood pressure was observed
      from the third month. Stabilized blood pressure observed within the first year
      persisted throughout the three years without tachyphylaxis. It was effective on
      SBP (-14.4%) and on DBP (-15%) while maintaining a stable heart rate both in the
      supine position or immediately upon standing or after 3 minutes in the standing
      position. Amongst diabetic and dyslipidemic patients, an absence of deleterious
      metabolic effects was noticed, parallel with the effectiveness. Tolerance was
      globally judged as good or very good by the investigating practitioners and the
      patients expressed an improvement in their feeling of well-being. In conclusion,
      from the level of effectiveness obtained and the low incidence of adverse
      effects, urapidil appears well adapted and easy to manage in a population with a
      particularly high cardiovascular risk.

PMID- 8734077
TI  - [Joint and systemic manifestations related to type 2 anti-mitochondrial
      antibodies].
AB  - The aim of the study was to assess the significance of type 2 anti-mitochondrial
      antibodies in patients with systemic and inflammatory rheumatic disease.
      Articular and systemic manifestations of 8 patients associated with type 2 anti
      mitochondrial antibodies are described. All the patients had hepatic
      abnormalities, and 5 of them disclosed a primary biliary cirrhosis. Articular and
      systemic manifestations were similar to those observed in primary biliary
      cirrhosis. Therefore, the finding of anti-mitochondrial antibodies in patients
      with systemic or inflammatory rheumatic disease implies research for other
      systemic manifestations such as primary biliary cirrhosis.

PMID- 8734078
TI  - [Anticardiolipin antibodies and Horton disease].
AB  - A prospective study, including 86 patients with giant cell arteritis proven by
      temporal artery biopsies, was performed to determine the prevalence of
      anticardiolipin antibodies, the antibody isotype, the relationship of antibodies
      to ischemic involvement and their evolution during corticosteroid treatment.
      Controls were obtained from 50 subjects without vasculitis or autoimmune
      disorders. Before treatment, 50% of patients' sera contained anti-cardiolipin
      antibodies (vs 8% in controls, p < 0.0001). These antibodies were IgG-ACL in 36%
      of patients and IgM-ACL in 17% of patients (vs respectively, 4% and 2% in
      controls). No significant association was observed between the incidence of
      ischemic ocular complications and the levels of anti-cardiolipin antibodies.
      During corticosteroid treatment, the level of anti-cardiolipin antibodies, mostly
      IgG class, decreased to become negative in 2 months. An increase of these
      antibodies was observed with the occurrence of relapses in four patients, after
      the end of corticosteroid therapy. The significance of IgG and IgM antibodies is
      different in giant cell arteritis. IgG antibodies may be markers of the course of
      this vasculitis.

PMID- 8734079
TI  - Antineutrophil cytoplasmic antibodies (ANCA) and abnormal angiograms in
      polyarteritis nodosa and Churg-Strauss syndrome: indications for the diagnosis of
      microscopic polyangiitis.
AB  - Microscopic polyangiitis (MPA) is one of the vasculitides previously included in
      the polyarteritis nodosa (PAN) group. A diagnosis of MPA is usually considered
      when glomerulonephritis and/or lung hemorrhage are present. Small-sized vessels
      are involved and this sign is considered, for some authors, to be the main
      diagnostic criterion. The present study attempted to define clinical,
      radiological and immunological characteristics of MPA and to separate them from
      classic PAN (c-PAN) and Churg-Strauss syndrome. We have shown that, in most
      cases, patients presenting microaneurysms and/or multiple vessel stenoses, which
      reflect medium-sized vessel involvement, do not have ANCA. Conversely, patients
      with glomerulonephritis have almost never had abnormal angiograms. Furthermore,
      the clinical characteristics of ANCA-positive patients also indicate small-sized
      vessel involvement. Although at present it is not possible to definitively
      separate MPA from c-PAN, our results show that ANCA should be considered
      diagnostic for MPA and, in most cases, should be an exclusion criterion for c
      PAN.

PMID- 8734080
TI  - [Risk indicators of reaginic allergy: relations between atopic dermatitis and
      serum specific IgE of various pneumallergens].
AB  - This study was conducted in 1,091 children and adolescents submitted to an
      allergy check-up for respiratory symptoms. All subjects had a research of IgE for
      Dermatophagoides pteronyssinus, cat and timothy grass pollen by CAP-System
      Pharmacia. Three hundred subjects had a personal history of atopic dermatitis.
      They were compared to the 791 others. No difference was found for age, sex,
      family history of allergic respiratory disease, breast feeding nor exposure to
      tobacco smoke. The IgE level was significantly enhanced among subjects with an
      history of atopic dermatitis, but this difference was due to a higher frequency
      of sensitisations. In subjects with at least one positive RAST (> 0.35 kIU/l) no
      significant difference was found (p = 0.41). The highest frequency of
      sensitisations in case of atopic dermatitis was exclusively related to the
      simultaneous sensitisation against all the three allergens. Such situation was
      more frequent when the atopic dermatitis was noted before the age of six months.
      On the other hand, the sensitisation severity, according to RASTs' classes, was
      independent of atopic dermatitis history. The author points out the necessity of
      strong primary preventive measures of pneumallergen environmental avoidance for
      all infants with atopic dermatitis.

PMID- 8734081
TI  - What is going to happen tomorrow regarding the antiphospholipid syndrome? Jean
      Charles Piette.

PMID- 8734082
TI  - [Hypothyroidism and blocking antibodies].

PMID- 8734083
TI  - [Association of dysfibrinogenemia and thrombosis. Apropos of a family (Fibrinogen
      Melun) and review of the literature].
AB  - We report a family with history of deep and superficial venous thrombosis. A
      large number of siblings had numerous episodes of deep venous thrombosis and less
      frequently arterial thrombosis. The most frequent site was lower limb.
      Dysfibrinogenaemia seems to play an essential role in predisposition to
      thromboembolism in this family, other known aetiologies having been excluded.
      Genetic studies of fibrinogen gene show a point mutation in the gamma chain (364
      Asp-Val), the site close to gamma 363 one of the sites involved in fibrin
      monomers polymerisation, although fibrinogen polymerisation is normal. Review of
      the 250 families with dysfibrinogenaemia published up to now shows that the
      prevalence of dysfibrinogenaemia in patients with a history of thromboembolism is
      about 0.7%, and that thrombosis is observed in about 10% of cases of
      dysfibrinogenaemia. Abortion risk seems to be increased in women with
      dysfibrinogenaemia. In contrast thromboembolism risk does not seem to be higher
      during pregnancy, but may be increased after delivery. The main mechanisms which
      have been proposed to explain thromboembolism observed in dysfibrinogenaemia are:
      resistance of the clot to thrombolysis; defective thrombin binding; enhanced
      platelet aggregation; increased blood viscosity, alteration of clot architecture.
      This family study together with the previously reported cases supports the
      hypothesis that there is a link between thrombosis and dysfibrinogenaemia in a
      small number of patients.

PMID- 8734084
TI  - [Huntington disease in a large family in southern Togo].
AB  - We report the clinical manifestations and the family in a large family in
      Southern Togo in which Huntington's disease is known to exist for the past 6
      generations. At present there are 8 patients in this family, 67 members
      descending from patients. This family study adds further information to our
      knowledge of Huntington's disease among black Africans.

PMID- 8734085
TI  - [Subclavicular skin metastasis of cervix cancer].

PMID- 8734086
TI  - [Paraneoplastic pyoderma gangrenosum].

PMID- 8734087
TI  - [Cutaneous vasculitis in sarcoidosis. 2 cases and review of the literature].

PMID- 8734088
TI  - [Osteitis secondary to toxic dermatitis caused by hydroxyurea. Apropos ofa case,
      review of the literature].

PMID- 8734089
TI  - [Neisseria mucosa endocarditis: apropos of a case and review of the literature].

PMID- 8734090
TI  - [Kidney insufficiency: toxicity factor of methyl-bromo-hydroxyquinoline].

PMID- 8734091
TI  - [Post-interval syndrome after carbon monoxide poisoning. Value of magnetic
      resonance imaging].

PMID- 8734092
TI  - [Cerebellar toxicity of cytosine-arabinoside in a young man following cerebral
      anoxia].

PMID- 8734093
TI  - [Wegener's granulomatosis, with successive lung and orbit involvement, occurring
      14 and 4 years before systemic symptoms as well as renal and sinusal sites].

PMID- 8734095
TI  - [Redaction of medical articles].

PMID- 8734094
TI  - [Wegener's disease disclosed by diabetes insipidus].

PMID- 8734096
TI  - [Cutaneous congruence in vertical scar mammaplasty with preservation of mammary
      base. Geometrical bases and initial study].
AB  - After a geometrical analysis studying the principle of the "inverted T" scar in
      mammoplasties and particularly the significance of the horizontal limb of the
      "T", the authors have developed a mammoplasty technique without a horizontal
      scar, based on the concept of preservation of the mammary implantation basis.
      Application of this principle to a preliminary series of 92 breasts in 48
      patients over a period of two years enabled the authors to perform cone resection
      of the mammary gland, while producing a congruent vertical scar not extending
      onto the inframammary sulcus. This technique, in contrast with other vertical
      scar mammoplasty techniques, does not generate any skin excess in the inframmary
      sulcus and avoids the need for skin resorption devices (cutaneous undermining,
      frowns), thereby decreasing the risk of morphological distortion and unsightly
      scars.

PMID- 8734097
TI  - [Triple muscular necklift and facelift; lifting of the orbicularis muscle, the
      platysma and zygomatic complex].
AB  - The last three decades have irreversibly changed the history of face-lifting.
      Based on the muscular approach of the Skoog, SMAS and "Composites" techniques and
      numerous recent anatomical studies, we decided to investigate the anatomical
      structures responsible for the first signs of ageing of the face. In addition to
      Hamra's techniques for orbicularis lifting and Connell's and Baker's techniques
      for platysma lifting, we have added our experience zygomaticus minor lifting in
      what we have called "the zygomatic complex". This technical combination of a
      triple muscle facelift is based on a very precise anatomical knowledge of the
      structures of the cheek which are described in the context of surgery for ageing
      of the face. We have performed this technique for almost 2 years, in 29 patients,
      with encouraging results. This study emphasizes the "preventive" nature of this
      operation, corresponding to the current request of young women, who request
      simple, rapid, outpatient procedures to maintain their thirty-year-old
      appearance. Consequently, the blind part of the procedure is performed
      endoscopically. It will probably provide even more comfort to our patients, in
      whom the satisfaction rate is remarkable, with negligible morbidity.

PMID- 8734098
TI  - [Experimental cervicoplasty: correction of the cervicomental angle by postero
      superior suspension of the hyoid bone. A study of 20 anatomical dissections].
AB  - The elegance of the cervical region is due to a certain balance between concave
      and convex surfaces, and is based on the presence of a well-defined cervicomental
      angle, generally between 90 degrees to 110 degrees. An excessively wide-open
      cervicomental angle makes the cervical profile inelegant. Numerous surgical
      techniques can improve this angle. There is however a certain limit to this
      correction: an excessively caudal and anterior hyoid bone. In this case the last
      proposal is a modification of the hyoid bone position in order to replace it in a
      backward and upper location. To achieve this goal we studied postero-superior
      suspension of the hyoid bone by plication of the tendon of the digastric muscle
      in 20 anatomic dissection. Each an dissection was controlled by x-ray of the
      profile of the cervical region before and after application of this technique.
      Cephalometric measures were performed and statistically analysed using the
      "Paired t-test" on Statview II. Analysis of the results after the plication of
      the tendon of the digastric muscle, demonstrated an average closing of the
      cervicomental angle of 25.6 degrees with an average ascent of the hyoid bone of
      13.27 millimeters and an average posterior transposition of 3.75 millimeters.
      This experimental cervicoplasty appears to be feasible. A precise surgical
      technique has been developed with an easy approach to the digastric tendon during
      standart faced lift procedures. The effect of the compression generated on the
      pharyngo-oesophageal complex by posterior transposition of the hyoid bone is
      unknown. This problem is now under investigation.

PMID- 8734099
TI  - [Lack of ossification of the skull after surgery for craniosynostosis. A study of
      risk factors apropos of 592 cases].
AB  - The Center for Craniofacial Anomalies of Necker-Enfants-Malades Hospital presents
      a retrospective study of the outcome of 592 patients who were operated for
      craniosynostosis between 1976 and 1991. The quality of ossification one year
      after operation is reported with a focus on influencing factors. The lack of
      ossification rate is 5% (30/592). Three parameters are identified as increasing
      the risk of poor osseous wound healing: local postoperative infection, forehead
      advancement especially when accomplished with resorbable osteosynthesis, and
      brachycephaly. On the contrary, repaired tears of the dura mater do not seem to
      pose a risk. Seventy five per cent of patients with local infection and 12.4% of
      forehead advancement presented a lack of ossification which is statistically
      significant (p < 0.001). Lack of ossification can compromise aesthetic and
      functional results. Decreasing postoperative infection and stable fixation may
      help to avoid it.

PMID- 8734100
TI  - [Outcome of nasal deviation in plgiocaphaly after bilateral frontocranial
      modeling in childhood].
AB  - The deviation of the nasal root is one of the major deformities in unilateral
      coronal synostosis. The objectives of this study are to evaluate the results of
      bilateral frontocranial remodeling on nasal deviation, focusing on the patient's
      age at the time of the operation. All the patients undergoing bilateral
      frontocranial remodeling for plagiocephaly and followed for a minimum of 5 years
      postoperatively, without any other craniofacial surgery were included in the
      study. Based on photographic data, 42 patients were assigned to one of 4
      morphologic categories: M1 = absence of nasal deviation; M2 = minor nasal
      deviation with no or minor revision required; M3 = severe nasal deviation with
      major alternative osteotomies required or performed; M4 = major nasal deviation
      with major craniofacial procedure and bone-grafting required or performed. Thirty
      nine patients presented with significant nasal deviation before surgery. Ninety
      two percent had a morphologic improvement and 62% had no residual nasal deviation
      (M1) more than 5 years after the procedure. The best results were obtained in
      patients operated between the ages of 12 and 24 months. All patients who
      underwent surgery during this period obtained improvement of the deformity, and
      90% had no residual deviation. In contrast, when patients were operated before
      the age of 12 months, 91% obtained improvement of the nasal deformity, and 57%
      were assigned to the M1 category. Additionally, surgery performed between the
      ages of 2 and 4 resulted in 67% of partial correction and 33% of ideal
      correction. The most difficult age group to correct were children 4 years and
      older. Of the 4 patients in this group, one required major secondary
      reconstruction (M3), and only one patient achieved complete correction. Although
      the endpoint for correction is an aesthetic assessment, cephalometric analysis
      was also performed in 29 cases. Comparison of the evaluations gave equivalent
      results.

PMID- 8734101
TI  - [Value of scaphal graft in secondary rhinoplasties].
AB  - The scaphal cartilaginous area is a most suitable anatomic site for cartilaginous
      graft harvesting. These grafts allow reconstruction of a flat dorsum, or a
      rounded dome, or alar cartilages or can be used for an extended tip graft. In
      some cases, both scaphes may be harvested. Raising of the grafts does not leave
      any sequelae when performed correctly. We have an experience of 20 cases. The
      main advantage of this graft is its flatness, which makes it ideal for the nasal
      dorsum. It has to be tailored, moderately crushed and included in a collagen
      "surgicel" in order to break the shape memory, slightly curved at its borders. We
      have used scaphal autografts in 15 cases of secondary rhinoplasties, 2 cases of
      cleft lip repair and in 3 cases of tertiary rhinoplasties. They solved most
      problems of missing cartilage, when minor defects had to be treated. These grafts
      will not solve major tissue defects which must be repaired by bone autografts,
      mostly iliac bone harvesting in our experience. The results of scaphal autografts
      are stable after 5 years. Resorption is moderate when the graft is correctly
      inserted, in an extramucosal pocket. The aesthetic result is maintained with a
      mean follow up of 2 years for 15 cases. The scaphal area of the ear therefore
      appears to be a favorable donor site for secondary, nose repair; it is easy to
      harvest, with inconspicuous morbidity and allows the raising of a good, flat and
      sculpturable material for cartilaginous nose replacement. Achieves the objectives
      of ore informed patients asking for artistic perfection.

PMID- 8734102
TI  - [Surgical strategy of osteocutaneous free transfer of the fibula in complex
      mandibular reconstructions: technical notes].
AB  - The fibula osteocutaneous free flap now has a recognized place in the therapeutic
      arsenal of microsurgical mandibular reconstructions. Based on a review of the
      literature and their own experience, the authors propose a preoperative and
      intraoperative strategy adapted to reconstructions of mandibular defects. The
      place of complementary investigations, the site of the skin flap, the choice of
      osteotomy, the type of fixation, and spatialisation of the skin flap are
      presented. They conclude on the excellent plastic and vascular qualities of the
      fibula flap in complex mandibular reconstructions.

PMID- 8734103
TI  - [Tissue expansion. Presentation of a model of external filling valve].
AB  - Based on their experience of facial tissue expansion, the authors present a model
      of an external filling valve and illustrate its advantages in 9 cases in which 13
      external valve were used: painful injection, absence of leakage, fast and
      confortable filling. The indications are sequelae of facial burns, face scars,
      treatment of orbito-temporal neurofibromatosis. The major advantage is rapid
      tissue expansion which reduces the problems of infection and skin loss.

PMID- 8734104
TI  - [Destructive paraffinoma of the breast and thoracic wall caused by paraffin
      injection for mammary increase. Apropos of 3 cases with review of the
      literature].
AB  - The injection of a high viscosity fluids into the tissues for cosmetic body
      contouring has been practised in the last four decades in the East and South-East
      of Asia. The injection of liquid paraffin for mammary augmentation was widely
      practised by surgeons, physician and even non medical people. Unfortunately, most
      of these cases ended by having different varieties of paraffinoma as a
      complication of a foreign body reaction. We report three cases of a destructive
      form of these paraffinomas ulcerating into both breasts and the anterior chest
      wall. One case was treated by bilateral mastectomy, radical excision of the
      anterior chest wall soft tissue and reconstruction by a vertical Rectus Abdominus
      Myocutaneous Flap. The second case had bilateral mastectomy and followed up for
      facial paraffinomas. The third case was just followed for up regular wound care
      as surgery was not indicated due to advanced age, poor general condition and the
      family request.

PMID- 8734105
TI  - [Use of bipedicled flap of the scalp to correct receding temporal hairline during
      secondary facelift].
AB  - The author describe a temporal scalp flap utilised during secondary face lift to
      correct receding temporal hairline.

PMID- 8734106
TI  - [Should lipoma be removed by liposuction? Apropos of a case of grade 1 myxoid
      liposarcoma of the shoulder].
AB  - Liposuction of a big lipoma--mostly on the chest and close to the upper limbs--is
      a fairly neat solution for such areas, which usually do not heal very well. The
      author reminds us of the fact that some liposarcomas may have the same features
      as a benign lipoma on inspection and palpation, and histology ("lipoma-like"). He
      recommends systematic biopsies and possibility grozen-section examination.

PMID- 8734107
TI  - [For a health policy in dermatology].

PMID- 8734108
TI  - [Tunisian pemphigus. Apropos of 70 cases. (Experience of the dermatology
      department of La Rabta Hospital 1974-1992)].
AB  - INTRODUCTION: Pemphigus frequently seen in Tunisia has specific characteristics
      distinguishing it from the European or American forms. Between 1974 and 1992, we
      observed 70 cases in the dermatology unit of the La Rabta University Hospital in
      Tunis. Most patients were young (mean age 39 yr), predominantly women (80%). Deep
      pemphigus (pemphigus vulgaris and vegetans) occurred in 56% and superficial
      pemphigus (seborrheic and foliaceus) in 44%. High-dose corticosteroids were given
      as initial treatment (1.4 mg/kg/day). Infectious complications were frequent.
      Mortality was 14%. Pemphigus in Europe and North America usually occurs in adults
      in the 50-60 year age range. Superficial forms are rare (2-10%). In Tunisia,
      pemphigus is similar to Brazilian pemphigus with high frequency and predominant
      superficial forms (pemphigus foliaceus).

PMID- 8734109
TI  - [Carriage of Staphylococcus aureus. A severity factor of erysipelas?].
AB  - INTRODUCTION: Occasional superinfection or co-infection with Staphylococcus
      aureus led us to search for S. aureus carriage prospectively in patients with non
      necrotizing bacterial dermophypodermitis, in particular erysipelas. PATIENTS AND
      METHODS: This prospective study included immunocompetent patients with bacterial
      dermophypodermitis without signs of toxicity or local manifestations suggesting
      necrotizing fasciitis. Bacteriology tests included: 1) direct immunofluorescence
      for streptococcus (groups A, C, G) on skin biopsies taken on day 0, 2) samples
      from the nasal orifices, the intergluteal fold, and potential skin portals for
      bacteriology culture, and 3) assay of antistreptolysine O and antistreptodornase
      B on day 0 and 15. RESULTS: The study group included 42 patients (23 females, 19
      males, mean age 64 +/- 3.5 yr). In 39 cases (93%) bacterial dermohypodermitis was
      located on the lower limb with a potential skin portal in 36 cases (86%). Sample
      culture, direct immunofluorescence or serology findings demonstrated presence of
      streptococci in 33 cases (79%). Nasal, intergluteal or potential portal were
      identified in 19 patients (45%) including 16 with demonstrated presence of
      streptococci. The rate of cure after oral pristinamycin did not vary
      significantly between carriers (79%) an non-carriers (91%) of Staphylococcus
      aureus. Drainage of a localized abscess was successful in 5 of 6 patients after
      initial failure of antibiotic treatment; 4 of them were carriers of S. aureus.
      CONCLUSION: This prospective study demonstrated that cutaneous-mucosal carriage
      of Staphylococcus aureus is frequent in patients with non-necrotizing
      dermohypodermitis. This carriage is not a factor of over-morbidity as shown in
      this group of infections largely dominated by erysipelas.

PMID- 8734111
TI  - [Diffuse lepromatous leprosy disclosed by cutaneous vasculitis. The Lucio
      phenomenon].
AB  - INTRODUCTION: Lucio's phenomenon, also called necrotizing erythema, is a rare
      acute manifestation which sometimes introduces diffuse lepromatous leprosy,
      almost exclusively in Central American populations. CASE REPORT: A 76-year-old
      polynesian man of chinese ethnic origin had necrotizing erythema for several
      months before development of Lucio's leprosy. The patient had necrotizing lesions
      of the lower limbs with large polygonal scars and poor general health status.
      Diagnosis was based on the discovery of acid-fast bacilli at the pathology
      examination of skin biopsies. The necrotizing zones appeared as cutaneous
      vasculitis with angiogenesis of the superficial dermis and presence of Hansen
      bacilli within the endothelium. DISCUSSION: This case of diffuse lepromatous
      leprosy, the first reported in the South Pacific, emphasizes the polymorphism of
      leprosy and the importance of recognizing rare clinical forms, especially in the
      tropics. Anti-Hansen drugs are effective.

PMID- 8734110
TI  - [Pristinamycin in the treatment of acute bacterial dermohypodermitis in adults.
      An open study of 42 patients].
AB  - INTRODUCTION: We recently demonstrated that oral roxithromycin is as effective as
      intravenous penicillin G in adults with erysipelas. We therefore evaluated the
      effectiveness of pristinamycin, an antibiotic which is very active on
      streptococci and Staphylococcus aureus, in non-necrotizing bacterial
      dermohypodermitis in adults. PATIENTS AND METHODS: This prospective open study
      was conducted in one center and included immunocompetent patients with bacterial
      dermophypodermitis without signs of toxicity or local manifestations suggesting
      necrotizing fasciitis. Bacteriology tests included direct immunofluorescence for
      streptococcus (groups A, C, G) on skin biopsies of the lesion before treatment.
      Patients were treated with pristinamycin (Pyostacine 500, 3 g/day until 10 days
      after apyrexia), and evaluated clinically on day 0, 2, 6, 8, and 15. Overall
      treatment effect was assessed on day 15. RESULTS: The study group included 42
      adults (23 woman and 19 men; mean age 64 +/- 3.5 yr). In 39 cases (93%), the
      bacterial dermohypodermitis was localized on the lower limb. The inflammatory
      lesion was well delimited, a characteristic feature of erysipelas, in 32 cases
      (76%). Sample culture, direct immunofluorescence or serology findings
      demonstrated presence of streptococci in 33 cases (79%). A single treatment with
      pristinamycin was successful in 36 patients, giving an overall rate of 86%.
      Drainage of a localized abscess was successful in 5 of 6 patients after initial
      failure of antibiotic treatment. CONCLUSION: This prospective study demonstrated
      the effectiveness of pristinamycin in non-necrotizing bacterial dermohypodermitis
      in the adult, especially in erysipelas. Overall effectiveness was comparable with
      that reported for penicillin G or macrolides in erysipelas.

PMID- 8734112
TI  - [Resistance to activated protein C disclosed by postphlebitic disease. Two
      cases].
AB  - INTRODUCTION: Recently, resistance to activated protein C has been discovered.
      Resistance to activated protein C appears to be the main cause of familial
      thrombosis. CASE REPORT: Two consecutive patients have been studied. Both have a
      venous insufficiency associated with eczema in one patient and venous ulceration
      in the second patient. The two patients had a personal and familial history of
      venous thrombosis. In both patients, a resistance to activated protein C was
      found associated with a mutation in the factor V gene in residue 506. DISCUSSION:
      When a personal or familial history of the venous thrombosis is associated with
      symptoms of venous insufficiency, resistance to activated protein C must be added
      to the search for proteins C, S and anti-thrombin III deficiency.

PMID- 8734113
TI  - [Systemic sensitization to 17-beta estradiol induced by transcutaneous
      administration].
AB  - INTRODUCTION: Transdermal administration of drugs to obtain a systemic effect may
      lead to allergic sensitization and compromise subsequent use via another
      administration route. OBSERVATION: A 52-year-old woman presented contact eczema
      with the transdermal therapeutic system Estraderm TTS50. Generalized eczema
      developed later after oral administration of an oestrogen derivative. Skin tests
      demonstrated allergic sensitization to 17 beta-oestradiol. DISCUSSION: Contact
      eczema due to transdermal therapeutic systems are usually caused by agents other
      than the active drug. Sensitization to the active drug raises the risk of
      generalized eczema and subsequent systemic complications. This risk must be taken
      into account when prescribing substitution hormone therapy for menopause.

PMID- 8734114
TI  - [Blau syndrome or familial form of sarcoidosis with onset during infancy].
AB  - INTRODUCTION: Blau syndrome is a granulomatous disease with dominant autosomal
      transmission. Skin, joint and ocular manifestations usually appear in childhood.
      CASE REPORTS: A father and his son had granulomatous disease with skin and joint
      manifestations beginning in childhood. Both patients had inflammatory
      polyarticular deformations of the small and medium sized joints with formation of
      synovial cysts. Skin manifestations were seen only in the son who presented
      diffuse micropapulous eruptions. Histology examination of the superficial and
      deep derma revealed an epithelioid granuloma without necrosis. DISCUSSION: Our
      case are similar to the syndrome described by Blau who recognized the familial
      nature of early onset sarcoidosis and probable autosomal dominant transmission
      together with joint deformation and development of synovial cysts without
      pulmonary involvement.

PMID- 8734115
TI  - [Local corticosteroid therapy in a severe form of pemphigoid gestationis].

PMID- 8734116
TI  - [A case for diagnosis: complicated frontal sinusitis].

PMID- 8734117
TI  - [A case for diagnosis: serpiginous hemangioma].

PMID- 8734118
TI  - [Resistance to activated protein C: a new cause of hypercoagulability].

PMID- 8734119
TI  - [Cartilaginous tumors and other cutaneous lesions].

PMID- 8734120
TI  - [Role of intralesional administration of bleomycin in the treatment of warts].

PMID- 8734121
TI  - [Question of the month: should direct immunofluorescence be performed in every
      case of papulous or pruriginous gestational dermatosis?].

PMID- 8734122
TI  - The value of placental pathology in studies of spontaneous prematurity.

PMID- 8734123
TI  - Sonography in the evaluation of the cervix during pregnancy.
AB  - Sonographic techniques have been developed to study the biometry and behavior of
      the cervix during pregnancy which have led to a better understanding of the
      pathogenesis of pregnancy loss and preterm birth. Nomograms have been developed
      for singleton and twin gestations, and associations between cervical sonographic
      characteristics and various adverse pregnancy outcomes have been observed. The
      new concept of 'relative' cervical incompetence suggests that the cervix may be
      an independent contributor to preterm birth. The incorporation of cervical
      sonography in management schemes for the prevention of pregnancy loss or preterm
      delivery has the potential to impact favorably on perinatal outcome.

PMID- 8734124
TI  - Use of antenatal corticosteroids for fetal maturation.
AB  - Corticosteroids used to enhance fetal maturation are one of the best studied
      interventions in perinatal medicine. The treatment has been shown to reduce
      neonatal morbidity and mortality. The intervention is also highly cost-effective.
      In this article, we review the evidence supporting the benefits of
      corticosteroids, controversial issues concerning their use, and current practice
      recommendations. The review will highlight the research presented at the recent
      National Institutes of Health Consensus Conference concerning corticosteroids.
      This research led the National Institutes of Health to advocate clinical practice
      guidelines on the appropriate use of corticosteroids.

PMID- 8734125
TI  - Management of severe preeclampsia.
AB  - Preeclampsia affects two patients, the mother and the fetus. Traditionally, women
      with severe preeclampsia have been delivered without delay, regardless of fetal
      considerations. Although delivery is appropriate therapy for the mother,
      aggressive management with immediate delivery of a fetus remote from term leads
      to high neonatal mortality and morbidity resulting from prematurity. Recent
      studies have shown favorable neonatal outcomes after conservative management of
      severe preeclampsia. Candidates for conservative management should be selected
      carefully and managed with intensive maternal and fetal monitoring at a tertiary
      perinatal center.

PMID- 8734126
TI  - The current status of Doppler sonography in obstetrics.
AB  - Searches for clinical applications of Doppler ultrasound in fetomaternal medicine
      continue. Currently, there are three main areas of interest: Doppler velocimetry
      of the umbilical artery, uterine artery and the fetal circulation (cerebral and
      venous blood flow studies). Evidence from randomized trials suggests that if
      women with suspected intra-uterine growth retardation or pre-eclampsia are
      offered Doppler studies of the umbilical artery, a clinically important reduction
      in perinatal mortality may be expected. On the other hand, screening of low-risk
      women either by umbilical artery Doppler or uterine artery Doppler is unlikely to
      be cost-effective. The study of other fetal vessels provides a fascinating
      insight into vascular changes that occur in fetal compromise, but it is not known
      whether the use of these tests will actually reduce perinatal mortality and
      morbidity. None of the Doppler indices used so far, including the middle-cerebral
      artery to umbilical artery ratio, has been able to match the performance
      characteristics of umbilical artery Doppler. Until clear evidence emerges on its
      benefit or otherwise, comprehensive fetal assessment by Doppler ultrasound should
      be used for research purposes only and results of these tests should not be used
      to guide clinical practice.

PMID- 8734127
TI  - Computerized fetal heart rate analysis and neural networks in antepartum fetal
      surveillance.
AB  - The use of computers for analysis of fetal heart rate has developed rapidly,
      enabling reproducible, objective analysis of fetal heart rate patterns. The
      problems of observer differences in visual assessment of fetal heart rate, and
      the continuum of antepartum and intrapartum fetal condition can be clarified
      through the use of such approaches. Computerized fetal heart rate analysis
      presents opportunities to perform precise evaluations of the effects of
      environmental conditions, medications, and disease states on fetal heart rate
      parameters.

PMID- 8734128
TI  - Intelligent fetal heart rate computer systems in intrapartum surveillance.
AB  - The intrapartum cardiotocogram has had a disappointing impact on clinical
      practice. Misinterpretation of the cardiotocogram not only causes an increase in
      unnecessary intervention but is also implicated in a large proportion of patients
      with birth asphyxia and avoidable perinatal morbidity. Over the past 10-20 years,
      groups have attempted to develop computer systems capable of analysing the
      cardiotocogram but with limited success. The likely explanation is that these
      conventional systems analyse the cardiotocogram in isolation from clinical
      factors. More recently, research has focused on the use of artificial
      intelligence techniques which can assess the whole clinical picture to support
      clinical decision making during labour. The current literature is reviewed and a
      system that has been validated by comparison of its performance with 17 experts
      is described.

PMID- 8734129
TI  - Advances in molecular diagnosis.
AB  - Approaches to the diagnosis of genetic disease using the tools of molecular
      genetics are being developed at a rapid pace as efforts to map the human genome
      progress. Technical challenges remain, however, in devising approaches to permit
      the wide diversity of pathogenic mutations to be identified in an efficient
      manner. Moreover, the possibility of population screening for carrier status for
      gene mutations raises important ethical and social questions. Major progress has
      been made in both areas and the list of disorders amenable to molecular diagnosis
      is expanding rapidly.

PMID- 8734130
TI  - Update in preimplantation genetic diagnosis: successes, advances, and problems.
AB  - The field of preimplantation genetic diagnosis has undergone significant advances
      since the report of the first birth from this method in 1990. The first birth in
      the USA was reported in 1992, as was the first successful diagnosis and delivery
      of a baby free of a single gene defect disorder (cystic fibrosis and then Tay
      Sachs). Investigators have now reported approximately 40 births worldwide from
      preimplantation genetic diagnosis using the polymerase chain reaction and
      fluorescent in-situ hybridization methods to analyze single cells removed from
      early cleavage stage preimplantation embryos. The International Working Group on
      Preimplantation Genetics meets annually to discuss progress and pitfalls in this
      field. Although preimplantation genetic diagnosis offers hope to patients at risk
      of transmitting disease, there are many technical hazards of this experimental
      procedure. Technical difficulties must be overcome in order for preimplantation
      genetic diagnosis to become a standard clinical tool. This review will highlight
      some of the recent advances and problems in the field of preimplantation genetic
      diagnosis.

PMID- 8734131
TI  - Modern management of Rhesus disease.
AB  - The cloning of the RhDCcEe complex has made it likely that the polymerase chain
      reaction will be incorporated into the modern management of rhesus sensitization.
      Currently, the accuracy of this technique is under evaluation. Its specific role
      in management protocols is not yet clear. The use of this technology will
      hopefully avoid the need for cordocentesis or serial amniocenteses in some
      patients.

PMID- 8734132
TI  - Fetal cardiology.
AB  - Several publications continue to address the topic of screening for fetal
      congenital heart disease with widely differing results. The ideal timing and
      method of fetal heart scanning is still under debate. An abnormal fetal heart
      position may indicate abnormality, particularly of the great arteries. The
      management of several problems that present to the fetal cardiologist are
      detailed in recent publications.

PMID- 8734133
TI  - Intra-uterine growth retardation.
AB  - Small-for-gestational-age fetuses are frequently detected in general obstetric
      practice. Despite remarkable improvements in our understanding and management of
      this group of conditions over the past 20 years, much more research is required.
      During the year reviewed in this article, advances were reported in
      identification, association/causation, relationship to maternal smoking, fetal
      endocrinology, clinical investigation and management, and these are discussed in
      turn.

PMID- 8734134
TI  - Spontaneous conception after repetitive in-vitro fertilization failure and Turner
      mosaicism.

PMID- 8734135
TI  - [Experimental prevention of deep venous thrombosis with low-molecular-weight
      heparin using implantable infusion devices].
AB  - We studied the effect of a fractionated heparin, Dalteparine Sodium, on the
      prevention of thrombosis of veins of the superior vena cava system catheterized
      by implantable infusion devices. Forty-six patients with solid or lympho
      proliferative tumors, whose clinical condition required installation of a such
      device, were successively included into the study in 1991. The anticoagulant was
      administered for one month following implantation at the dosage of 2,500 anti-Xa
      units per day. The development of deep vein thrombosis was investigated by
      systematic Doppler ultrasound before the first and third months and at 1 year.
      Three early (D9, D12 and D16) and asymptomatic thrombosis were diagnosed (6.5%).
      This rate, although clearly more favourable, was not significantly different (p =
      0.254) from the rate of 15.2% previously reported in a group of 72 comparable
      patients, but who did not receive preventive treatment. These results demonstrate
      the necessity and feasibility of a randomized study on a larger number of
      patients testing several protocols, before concluding on the efficacy of this
      type of preventive treatment.

PMID- 8734136
TI  - [Sneddon syndrome and mitral valve disease].
AB  - The authors report the case of a 37-year-old woman with widespread livedo and
      transient cerebral ischaemia (Sneddon's syndrome). The patient had also mitral
      valve disease who required commissurotomy two years ago. The research of
      anticardiolipin antibodies was negative. The relations between Sneddon's
      syndrome, antiphospholipid antibodies and valve lesions are discussed.

PMID- 8734137
TI  - [Myocardial diverticulum of the left ventricle. Review of the literature apropos
      of a case].
AB  - Left ventricular myocardial diverticular rare, as they represent 0.05% of all
      forms of diagnosed congenital heart disease. The circumstances of diagnosis are
      as variable as the multiplicity of symptoms with which they are associated.
      Consequently, treatments (or very often conservative management) are also varied
      and a standardized procedure has not been defined in this field, apart from a
      common sense approach.

PMID- 8734138
TI  - [Cardiac tamponade disclosing systemic lupus erythematosus].
AB  - Cardiac tamponade secondary to systemic lupus erythematosus is rare and has a
      very serious prognosis. The authors report a case of cardiac tamponade confirmed
      by echocardiography, which constituted the presenting sign of systemic lupus
      erythematosus in a 20-year-old patient, who required emergency pericardial
      aspiration. The diagnosis of systemic lupus erythematosus was established on the
      basis of the combination of pericardial involvement, non-erosive arthritis,
      leukopenia with lymphopenia, presence of LE cells and anti-native DNA antibodies
      and positive antinuclear antibody titre of 1/2560. The clinical course was
      favourable in response to 3 months of corticosteroid treatment. The possibility
      of SLE should be considered in any case of cardiac tamponade in a young patient
      in which the aetiology is not explained.

PMID- 8734139
TI  - [Evaluation of amlodipine in stable effort angina. Comparison with diltiazem in
      terms of efficacy, tolerability and maintenance of the anti-ischemic action 24
      hours after the last dose].
AB  - 83 patients were enrolled in a multicentre, randomized, open study to assess the
      efficacy of amlodipine in stable effort angina. Preselected patients were
      submitted to a one-week placebo wash-out period during which only nitrates or
      molsidomine were authorized. Patients were then randomized to receive either 5 mg
      of amlodipine as a morning dose, or 180 mg of diltiazem in three divided doses.
      After two weeks, the dosage was able to be increased (according to clinical
      efficacy) to 10 mg of amlodipine as a single dose or 240 mg of diltiazem in four
      divided doses. The antianginal efficacy of these two treatments was essentially
      evaluated in terms of the results of stress tests (ST) conducted at the end of
      the second week and fourth week of active treatment: and 24 hours after the last
      dose of the drug. The results of 63 patients who scrupulously complied with the
      protocol showed that amlodipine and diltiazem corrected or improved the ST
      parameters (time to onset and amplitude of ST depression, duration of ST, work
      performed). The anti-ischaemic action of amlodipine was maintained for at least
      24 hours after the last dose and therefore provides better security (by covering
      the entire 24-hour period) and better compliance (by tolerating a dose omission
      of several hours).

PMID- 8734140
TI  - [Lupus and sun].

PMID- 8734141
TI  - [Chronic progressive external ophthalmoplegia with mitochondrial anomalies.
      Clinical, histological, biochemical and genetic analysis (9 cases)].
AB  - We report the clinical signs and histological findings in nine patients with
      mitochondrial ocular myopathies. There were four males and five females. Of age
      ranging from 47 to 82 years. A more often asymetrical ptosis was in all cases of
      chronic progressive external ophtalmoplegia (CPEO), but muscle weakness in limbs
      was not usual. The prognosis in this group was good, but ubidecarenone (150 mg/d)
      used for two cases, did not improve ophtalmoplegia. The serum creatine kinase was
      normal in eight of nine cases and electromyography showed myopathic changes in
      three cases. Histoenzymatic analysis of the muscle biopsy and biochemical studies
      of mitochondria isolated from the muscle sample demonstrated mitochondrial
      myopathy associated with partial deficiency of complexes I and/or IV of the
      electron transfer chain. One of seven patients studied had single deletion by
      Southern blot analysis, in a heteroplasmic state and another an A-->G transition
      at position 3243 within the mitochondrial tRNA leu (UUR) gene. Chronic
      progressive external ophtalmoplegia, without large deletion, may have abnormality
      in other coding regions of mt DNA such as tRNA, rRNA or protein genes.

PMID- 8734142
TI  - [Classical anticoagulant treatment of venous thromboembolic disease in cancer
      patients. Apropos of a retrospective study of 71 patients].
AB  - In order to evaluate the efficiency of classical anticoagulant therapy for venous
      thromboembolic disease in cancer patients, we retrospectively analysed 71
      patients treated with intravenous heparin first and then with antivitamin K.
      After a mean follow-up of 185 +/- 25 days, 23 patients (33%) were dead; nine
      patients (12%) had suffered from major haemorrhagic complications, which were not
      fatal, four of which were due to heparin overdosage; 17 patients (24%) showed
      recurrent venous thromboembolic disease. According to univariate statistical
      analysis, risk of major bleeding was not associated with the presence of either
      thrombocytopenia, abnormal blood coagulation, metastases and/or any other
      hemorrhagic risk factors; recurrence of venous thromboembolic disease was not
      associated with the presence of other risk factors for venous thromboembolic
      disease, nor with the presence or absence of metastases and/or of ongoing
      chemotherapy. Such results suggest that classical anticoagulant therapy for
      venous thromboembolic disease in cancer patients is neither effective nor safe.
      The present retrospective study underlines needs for further prospective analyses
      in order to evaluate potential benefit from other therapeutic strategies, such as
      use of low molecular weight heparins and/or vena cava filter placement.

PMID- 8734143
TI  - [Chronic myeloid leukemia, biological aspects].
AB  - Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a stem
      cell, involving myeloid, erythroid, megacaryocyte, lymphoid B-cells and "natural
      killer" cells. The hallmark of CML is the Philadelphia (Ph) chromosome which is a
      shortened chromosome 22 (22q-) resulting from a reciprocal translocation
      involving chromosome 9 and chromosome 22, designed t (9;22) (q34;q11). This
      translocation juxtaposes parts of two genes; ABL on chromosome 9 and BCR
      (breakpoint cluster region) on chromosome 22. Transcription of the BCR/ABL fusion
      gene results in an hybrid mRNA that is translated into a 210 kDa or 190 kDa
      protein, depending on the location of the breakpoint in the bcr region. This
      protein plays a key role in CML: its tyrosine-kinase activity, that differs from
      the normal ABL product, may be involved in leukemic cell growth. Nonetheless, the
      loss of the negative cell growth regulation by c-ABL, or BCR/ABL fusion protein
      interaction with other cellular genes (such as RAS or c-MYC) could also be
      involved in CML pathophysiology. A better understanding of the molecular
      mecanisms of CML could lead to specific treatment, such as tyrosine-kinase
      inhibitors, synthetic oligodeoxynucleotides, or site-specific DNA-binding
      proteins designed against BCR/ABL oncogenic fusion sequence.

PMID- 8734144
TI  - [Prognostic factors in early inflammatory arthritis].
AB  - Rheumatoid arthritis (RA) and spondylarthropathies are the most frequent chronic
      inflammatory arthritides. RA is a potentially severe disease which causes a
      functional handicap in nearly half the patients 10 years after the first clinical
      symptoms. However RA is a heterogenous disorder characterized by wide variations
      in clinical manifestations, disease course and response to therapy. No prognosis
      factor has been identified and universally accepted and validated. Markers of
      prognosis would be highly appreciated by clinicians who could then more closely
      adapt their management decisions to the disease potential. Clinical and
      biological data collected to date have provided a limited amount of information.
      Nevertheless, ESR, CRP and rheumatoid factor titer appeared to be the most
      powerful available indicators of prognosis at the early stage of the disease.
      Recent progress in molecular biology strongly suggests that genetic markers (HLA
      DRB1 alleles) could be correlated with disease severity and it would appear
      possible to distinguish immunogenetically homogeneous subpopulations of patients
      with RA. Serum concentrations of specific cartilage and bone molecules reflecting
      tissue turnover could correlate to rate of joint destruction. Finally a
      combination of the most pertinent markers could determine a "score of severity"
      of the disease. In spondylarthropathies, limited information is available at
      present. The variables which were usually correlated with disease severity are:
      onset before 16 years of age, hip arthritis, ESR, limitation of lumbar spine,
      sausage-like finger or toe, oligoarthritis, poor efficacy of nonsteroidal
      antiinflammatory drugs and rapid evolution during the first 2 years. Genetic
      factors could also have prognosis value that should be clarified.

PMID- 8734145
TI  - [Relapsing polychondritis, thrombosis and antiphospholipid antibodies].
AB  - The authors report a case of relapsing polychondritis associated with
      antiphospholipid antibodies. The initial manifestations were recurrent venous
      thrombosis which occurred prior to the chondritis. Antiphospholipid antibodies
      are found in various diseases, some of which are sometimes associated to
      relapsing polychondritis. However, antiphospholipid-antibodies have not yet been
      reported in this disease.

PMID- 8734146
TI  - [Multiple digestive involvement in visceral leishmaniasis in a patient with HIV
      infection: favourable course with itraconazole].
AB  - We report a case of visceral leishmaniasis due to Leishmania infantum in a 35
      year-old patient with acquired immunodeficiency syndrome who complained of
      chronic diarrhea. Biopsy specimens of gastric and duodenal mucosa and bone marrow
      aspirate led to the diagnosis. Enterocytozoon bieneusi, fortuitously found in the
      duodenal mucosa, did not seem to be the causative agent of diarrhea in this case,
      but its association with visceral leishmaniasis is rare. A treatment with
      itraconazole brought about a sustained clinical remission.

PMID- 8734147
TI  - [Thrombotic microangiopathies in HIV infection: 4 cases].
AB  - Thrombotic microangiopathy (TMA) has been rarely described in HIV-infected
      patients. We report four cases of TMA during HIV infection and we analyse
      clinical, biological, etiologic, therapeutic and evolutive aspects of these four
      cases. Initial symptomatology is non specific and diagnosis is often delayed.
      Peripheric thrombopenia with haemolytic anemia and renal failure must be
      suggestive of the diagnosis. TMA can be present at any stage of HIV infection.
      Physiopathological mechanism of TMA during HIV infection remains unclear. These
      cases lead to suspect the role of opportunistic infections, neoplasia or HIV
      directly by endothelial injury or indirectly by cytokines secretion. Therapy of
      TMA is not different from non-HIV patients. Improvement with treatment must be
      obtained but long-term prognosis remains poor in account of HIV infection.

PMID- 8734148
TI  - [Spiral scanners: principles and clinical prospects].
AB  - Helical computed tomography (CT) involves continuous patient shifting during X
      ray source rotation and data acquisition. As a result, a volume data set is
      obtained in a short period of time. An entire examination can be completed in a
      single breath hold, without additional radiation exposure, optimizing enhancement
      with intravenous contrast material. By overcoming some of the constraints of
      conventional CT, helical CT has advanced prospects, including multiplanar
      reconstruction and CT angiography, as reviewed in this article. There are
      undergoing studies to confirm these preliminary findings: its clinical
      applications are currently evolving.

PMID- 8734149
TI  - [Present status of cortisone myopathy].
AB  - Steroid myopathy is one of the various side effects of prolonged treatments,
      particularly with the 9 alpha fluorinated steroids. The receptor protein probably
      plays a major role with a decrease in protein synthesis. There is no mean to
      detect this myopathy before clinical signs appear. Neither muscular testing nor
      enzymes nor electromyography give arguments and muscular biopsy is aggressive.
      Low density scanner and MNR could help diagnosis. Frequency of disease is not
      known. A total cumulative maintenance steroid dosage of 400 mg can be sufficient.
      Proximal muscles are usually involved, quadriceps and other pelvic girdle muscles
      being more severely affected. Fast twitch glycolytic type IIB fibers are
      particularly susceptible. Physical exercise is effective in preventing myopathy.
      Nevertheless, no special rehabilitation program has been tested for the moment in
      human beings.

PMID- 8734150
TI  - [Gangrene with normal pulse].

PMID- 8734151
TI  - [Meningoradiculitis in systemic lupus: role of antiphospholipid antibodies?].

PMID- 8734152
TI  - [Peritoneal tuberculosis: late complication of BCG treatment for bladder
      carcinoma].

PMID- 8734153
TI  - [Association of pyoderma gangrenosum with hepato-pancreatic involvement in
      rheumatoid polyarthritis].

PMID- 8734154
TI  - [Atlanto-axial osteoarthritis].

PMID- 8734155
TI  - [Splenic lesion and multiple monoclonal gammopathies associated with primary
      cytomegalovirus infection in an immunocompetent adult].

PMID- 8734156
TI  - [Apropos of neoplastic cachexia].

PMID- 8734157
TI  - [International symposium on treatment of cardiac arrhythmia. Current trends.
      Lille, France, November 2-3, 1995].

PMID- 8734158
TI  - Is there a need for new antiarrhythmic drugs?
AB  - Currently available antiarrhythmic drugs were developed at a time when the basic
      mechanisms underlying most arrhythmias were conjectural at best. Indeed, the
      molecular targets upon which drugs act to prevent (or to exacerbate) arrhythmias
      are only now being defined. Thus, recent advances in the treatment of patients
      with arrhythmias have emphasized non-pharmacologic approaches, which use new
      information on the pathophysiology of specific arrhythmias to deliver targeted
      therapies. For some arrhythmias, such as atrial fibrillation, it seems likely
      that drug therapy will remain an important part of treatment. With increasing
      cellular and molecular understanding of the determinants of normal and abnormal
      cardiac electrogenesis, it should be possible to develop effective and safer
      drugs for the treatment of cardiac arrhythmias.

PMID- 8734159
TI  - [Antiarrhythmic drugs in paroxysmal atrial fibrillation. When and how?].
AB  - Atrial fibrillation (AF), carries a serious risk of systemic embolic
      complications, especially cerebral. Antiarrhythmic therapy is the most used
      method for restoring or maintaining sinus rhythm, and for preventing recurrences
      or of controlling the ventricular response. A clinical classification was
      recently suggested to define when to use antiarrhythmic drugs. In a first episode
      of symptomatic AF (Class I), it is not possible to assess the chances of
      recurrence and preventive antiarrhythmic therapy would not seem justified. In
      recurrent paroxysmal AF, the arrhythmias may be asymptomatic (Class IIa) and
      antiarrhythmic therapy may be questionned. When the attacks are infrequent (< 1
      every 3 months, Class IIb), episodic pharmacological intervention to restore
      sinus rhythm or to slow the ventricular rate may be valuable, but the efficacy
      and safety of such treatment should be assessed. In Class IIc, appropriate
      antiarrhythmic treatment to prevent recurrence is often indicated. Atrial
      fibrillation resistant to one or more antiarrhythmic drugs (Class III) may also
      be subdivised into three subgroups as for Class II. In addition to the use of
      alternating of antiarrhythmic drugs not previously used, it is justifiable to
      consider investigations to determine the mechanism of resistant AF use only drugs
      of the which slow the ventricular rate. The choice of antiarrhythmic drug may be
      guided by the concepts of the Silician Gambit, taking into consideration the
      mechanism of AF and the therapeutic objective. In AF, the mechanism is reentry,
      the vulnerable parameter the atrial refractory period. To increase the refractory
      period, the target should be the sodium or potassium currents. The status of left
      ventricular function is an important parameter in the choice of an antiarrhythmic
      agent.

PMID- 8734160
TI  - Is there an effective pharmacological treatment in the prevention of vasovagal
      syncope?
AB  - Many studies have claimed successful pharmacological prevention of vasovagal
      syncope in open formats with a wide variety of drugs. However, when therapy has
      been subjected to clinical trial to date no drug has shown any real benefit but
      it is necessary to add that the means of assessment leave much to be desired.
      These are repeat tilt testing, reported symptoms, analysis of syncopal burden in
      a population and time to syncopal recurrence. The disadvantages of any parameter
      derived from tilt testing is that its reproducibility is open to question and
      other aspects such as tilt duration before syncope have been inadequately
      investigated. With respect to symptom recurrence there are limitations because of
      the well known occurrence of vasovagal syncope in clusters and the long trial
      time that it is necessary because of relatively infrequent attacks. Furthermore,
      there is a placebo effect of the investigation of syncope which may delay the
      first recurrence. The first large trial is now underway and it is hoped that it
      may offer a method of prevention of vasovagal syncope which is both effective and
      acceptable.

PMID- 8734161
TI  - Nonsustained ventricular tachycardia in ischemic heart disease: when and which
      pharmacological treatment?
AB  - Nonsustained ventricular tachycardia is not uncommon both in the presence and
      absence of organic heart disease and in the latter situation, is usually not
      associated with an increased risk. However, in patients with ischemic heart
      disease, especially in the post-infarction period, nonsustained ventricular
      tachycardia is associated with an increased risk of sudden, and possibly non
      sudden, cardiac death. Several non-invasive and invasive tests have been
      utilized, individually or in combination, to risk stratify those patients. Left
      ventricular ejection fraction, the signal averaged electrocardiogram, and
      especially programmed ventricular stimulation have been commonly utilized to
      identify those patients at high risk for malignant tachyarrhythmias and to
      evaluate the potential benefit from antiarrhythmic treatment. At present,
      however, there is no consensus as to the best strategy to identify and treat high
      risk patients. Several ongoing multicenter clinical trials may eventually provide
      such guidelines. In the meantime, an algorithm for the management of those
      patients is suggested.

PMID- 8734162
TI  - Post-infarction sustained ventricular tachycardias. The role of drugs and methods
      for assessing antiarrhythmic efficacy.
AB  - Sustained monomorphic ventricular tachycardia is the most important
      tachyarrhythmia post-infarction. It is re-entrant and is amenable to examination
      by programmed stimulation. Despite several shortcomings, this technique remains
      an important method for predicting the long term efficacy of antiarrhythmic
      drugs. Ventricular ectopic beat suppression and indirect tools for evaluating the
      electrophysiological conditions of the myocardium (signal averaging, heart rate
      variability, QT dispersion, etc.) have a useful but limited role for selecting
      and assessing therapy. Implantable cardioverter defibrillators, surgery and
      catheter ablation are important treatment options but antiarrhythmic drugs are
      the first line approach. Their efficacy is not high but for those in whom they
      work, they offer acceptable levels of reliability and safety.

PMID- 8734163
TI  - Risk assessment and prevention of sudden cardiac death in hypertrophic
      cardiomyopathy.
AB  - One of the principle aims in the assessment of the patient with hypertrophic
      cardiomyopathy is assessment of risk for sudden cardiac death. Conventional risk
      stratification is reviewed together with other non-invasive techniques such as
      exercise physiology; the signal averaged electrocardiogram and heart rate
      variability. The role of arrhythmias in the pathogenesis of sudden cardiac death
      in hypertrophic cardiomyopathy is reviewed together with the role of programmed
      ventricular stimulation. A novel electrophysiological technique is described in
      detail which aims to measure the electrophysiological effects of myocardial
      disarray and seems safer and more sensitive and specific than conventional
      electrophysiological techniques. Current therapeutic strategies are discussed
      including the role of drugs, the implantable cardioverter defibrillator, surgery
      and dual chamber pacing.

PMID- 8734164
TI  - Mechanisms and management of congenital and acquired long QT syndromes.
AB  - The long QT syndromes can be divided into congenital and acquired forms. Early
      afterdepolarizations have been identified as triggering mechanisms for both
      congenital and acquired QT syndromes but reentry may play a role in the
      perpetuation of the ventricular tachycardia, torsade de pointes. Studies of the
      ionic mechanisms of early afterdepolarizations have implicated L-type Ca2+
      current, persisting Na+ current, and Na+:Ca2+ exchange current related to Ca2+
      loading. Different ionic mechanisms may be operative in early
      afterdepolarizations occuring at different levels of membrane potential in the
      setting of prolonged repolarization by blocking K+ currents or maintaining non
      inactivating Ca2+ or Na+ currents or in early afterdepolarizations due to
      adrenergic stimulation. In the congenital long QT syndromes, two mutations have
      recently been discovered in the genes SCN5A and HERG which encode respectively
      the Na+ channel and a K+ channel conducting the current IKr. It is postulated
      that the SCN5A mutation leads to a problem with inactivation of Na+ current. In
      the case of the HERG mutation, the K+ current appears to be diminished. In the
      case of the acquired long QT syndromes, the therapeutic challenge is to maintain
      the prolonged repolarization but to interrupt the arrhythmogenic cascade. Current
      therapies for torsades de pointes include speeding of the heart rate, which
      enhances K+ current, and Ca2+ blockers or Mg, also a Ca2+ blocker. In the
      congenital long QT syndromes, therapy in the past has been directed toward
      reducting adrenergic influence either by betablockade or left cardiac
      sympathectomy. Recent discoveries open other possibilities such as Na+ channel
      blockers and methods to increase IKr such as elevation of extracellular K+.

PMID- 8734165
TI  - [Radiofrequency ablation: physical bases and principles].
AB  - Radiofrequency currents are the reference physical agent for endocavitary
      ablation, especially of supraventricular tachycardias. They are delivered in a
      continuous mode or sinusoidal waves. Because of the high frequency between 200
      and 3,000 kHz there is no stimulation of the neuromuscular cells. The mechanism
      of the resulting lesion is essentially related to heating of the biological
      surroundings of the active electrode. The temperature increase remains localised
      around the active electrode and its kinetics are progressive, which implies close
      and stable contact between the active electrode and the tissues. The lesional
      effect is obtained 60 to 90 degrees C in order to avoid the deleterious effects
      induced by temperatures of over 100 degrees C: boiling, coagulation, vaporization
      and carbonization of the tissues leading to an increase in impedence. The volume
      of lesions depends on many factors which are sometimes difficult to control in
      vivo. It is more closely correlated to the temperature of the active electrode
      than to the parameters of delivery (power, duration ...). The histological
      lesions correspond to scar tissue which respects the surrounding architecture.
      The major technological innovations of this method have resulted in an increase
      in the volume of the lesions produced, a reduction in the frequency of
      undesirable effects such as the formation of coagulum and in an immediate
      evaluation of the anatomic lesional effect. They have consisted in the
      introduction of specific electrodes and of systems of monitoring the electrical
      and thermal effects with the use of imaging techniques such as endovascular and
      transoesophageal echocardiography and angioscopy. New indications will require
      development of specific catheter-generator equipment to create lesions of size
      and shape adapted to the arrhythmogenic substrate.

PMID- 8734166
TI  - [Catheter ablation and modulation of the atrioventricular junction; current
      aspects].
AB  - Ablation of the atrioventricular junction consists in creating a therapeutic AV
      block to facilitate the treatment of symptoms caused by atrial arrhythmias
      refractory to drug therapy. The technical performance of ablation has been
      improved by restricting the indication to atrial fibrillation, by using
      radiofrequency currents, by choosing a nodal rather than His bundle ablation
      site, and by improving the function of cardiac pacemakers (rate adapting, back
      up). The functional results are excellent but the outcome is punctuated by rare
      cases of sudden death, the cause of which is not fully understood (dependance,
      ventricular arrhythmias, ...). To avoid permanent pacing, it has been suggested
      that atrioventricular conduction should be modulated rather than completely
      interrupted. Modulation of the fast pathway has been shown to be ineffective;
      that of the more complex, slow pathway, seems to be more promising. Although this
      obviates the need for a pacemaker, it does not suppress irregularity of the
      ventricular rhythm, the main cause of symptoms in paroxysmal atrial fibrillation
      and of the haemodynamic changes associated with permanent atrial fibrillation.

PMID- 8734167
TI  - Radiofrequency catheter ablation of atrial flutter circuits.
AB  - Common atrial flutter is due to reentrant activation of the right atrium,
      rotating around anatomic structures and areas of functional block, in
      counterclockwise direction in the frontal plane. The myocardium between the
      inferior vena cava and the tricuspid valve is critical to close the activation
      circuit, and ablation of this isthmus by catheter-delivered radiofrequency can
      interrupt flutter, and eventually destroy the circuit, preventing recurrence of
      the arrhythmia. Flutter interruption does not mean complete isthmus ablation, and
      the procedure endpoint is to attain flutter non-inducibility, and isthmus block.
      Despite non-inducibility, flutter may recur, and new procedures may be needed for
      complete ablation. Atrial fibrillation can occur in up to 35% of the cases during
      follow-up but is generally well controlled with drugs that were ineffective
      against flutter before ablation. Some atypical atrial flutters show circular
      right atrial activation, using the same circuit in a clockwise direction, and
      these can also be interrupted by ablation of the inferior vena cava-tricuspid
      valve isthmus. Other atypical flutters can have different anatomic substrates in
      the right or left atrium, and mapping has to define specific isthmuses as
      ablation targets in each case. Left atrial flutter remains inaccessible to
      ablation.

PMID- 8734168
TI  - [Endocavitary ablation of nodal reentrant tachycardia].
AB  - Atrioventricular nodal reentrant tachycardias which, for a long time, could only
      be treated medically, may now benefit from catheter ablation. The rapid
      retrograde pathway was an effective initial target but carried a risk of complete
      atrioventricular block of about 10%. Nowadays, most operators deliver the
      radiofrequency energy (endocavitary cautery) to the slow nodal pathway. Different
      techniques of guidance (anatomical, electrophysiological, rapid potential, slow
      potential) are associated with high success rates: 90 to 100%. However,
      experimental studies suggest that the slow potentials arise from transitional
      cells within the tachycardia circuit (the anatomical substrate of the slow
      pathway). There is still a risk of complete atrioventricular block (1 to 5%)
      which should be clearly explained to patients referred for ablation of this
      constantly benign arrhythmia.

PMID- 8734169
TI  - [Radiofrequency ablation of the atrioventricular accessory pathways. Value of
      unipolar and bipolar recordings].
AB  - Radiofrequency catheter ablation has become the treatment of choice of
      arrhythmias related to accessory atrioventricular pathways. The reported success
      rate is well over 90%, irrespective of the localisation of the accessory pathway,
      and serious complications are rare. A basic principle of the technique is the
      limitation of the number of applications of radiofrequency energy during a
      session of ablation and this requires mapping to determine the ideal site using
      various electrographic parameters. With regards to bipolar recordings, they
      include: the atrioventricular conduction time, localisation of the ventricular
      pole of the accessory pathway, recording the accessory pathway potential, the
      atrial pole of the accessory pathway, and stability of the catheter position.
      However, the parameters are not readily reproducible and the positive predictive
      value for successful ablation is low. The use of unipolar electrograms could
      therefore represent a fundamental step in improving the localisation of accessory
      pathways and thereby reducing the number of useless applications of
      radiofrequency energy.

PMID- 8734170
TI  - [Radiofrequency catheter ablation of ventricular tachycardia].
AB  - Radiofrequency energy was used for the ablation of chronic recurrent ventricular
      tachycardia (VT) in 58 patients who were divided into two groups: 44 cases with
      structural myocardial disease (36 men and 8 women: mean age 55 years; range: 14
      to 85 years) with an average left ventricular ejection fraction of 38% (range: 15
      to 80%): these patients had myocardial infarction (28 cases), arrhythmogenic
      right ventricular dysplasia (11 cases), idiopathic dilated cardiomyopathy (2
      cases), operated congenital heart disease (2 cases) and operated valvular heart
      disease (1 case). The clinical success rate after the first session of
      radiofrequency ablation was 34%. When (according to our modified protocol of
      fulguration) 160 joule cathodal shocks were delivered to the same catheter
      previously used for RF ablation during the same session or secondarily (13
      cases), the success rate increased to 76%. The average follow-up period of the 37
      survivors was 16.7 months. The second group consists of 14 cases without
      structural myocardial disease (10 men and 4 women, mean age 41 years, range 14 to
      69 years) with an average left ventricular ejection fraction of 61%. These
      patients had idiopathic ventricular tachycardia (10 cases) and verapamil
      sensitive ventricular tachycardia (4 cases). The primary success of
      radiofrequency ablation alone was 43%. When combined with fulguration during the
      same of radiofrequency ablation alone was 43%. When combined fulguration during
      the same of at a later session, the success rate increased to 71.3%. The average
      follow-up period of the 13 survivors was 19 months (range 0.3 to 39 months). No
      significant difference was observed between the groups with or without structural
      myocardial disease after radiofrequency or fulguration ablation, not only with
      respect to global results but also after analysis of subgroups with, for example,
      post-infarction ventricular tachycardia or arrhythmogenic right ventricular
      dysplasia. However, clinical success was obtained after a single session of
      radiofrequency ablation alone in 8 of the 9 cases of incessant ventricular
      tachycardia in patients with structural myocardial disease.

PMID- 8734171
TI  - [Value of mapping in surgical treatment of ventricular tachycardia].
AB  - Surgery may be proposed for patients with a localised aneurysm or akinesia for
      treatment of monomorphic ventricular tachycardia resistant to antiarrhythmic
      therapy after myocardial infarction. The multiplicity of tachycardia forms in the
      same patient, the variability of their mechanism which is not necessarily limited
      to the subendocardia layers, require mapping to guide the surgeon in the
      destruction of the anatomical substrates. In a series of 57 ventricular
      tachycardias recorded in 17 patients with myocardial infarction the authors
      demonstrated that a system of computerised mapping of the epicardial and
      endocardial regions optimised the results of this form of surgery. Mapping
      localised, sometimes at a distance from the scar, classical subendocardial
      reentry, implicated on occasion the mitral papillary muscle in the mechanism or a
      tachycardia in cases of inferior or lateral infarction and localised the reentry
      in the epicardium of the lower layers of the septum. The identification of these
      "atypical" mechanisms significantly improves the number of patients without
      inducible arrhythmias after surgery (from 50 to 87% in the authors' experience),
      without changing the operative mortality. The only really curative approach
      because of the limitations of catheter ablation, this surgery is a complementary
      method to implantable defibrillators in the management of post-infarction
      ventricular tachycardia.

PMID- 8734172
TI  - Surgical treatment of ventricular tachycardia. Indications and results.
AB  - Despite the excellent results achieved with the endocardial resection procedure
      in the management of patients with life-threatening ventricular tachycardia. Most
      surgical electrophysiology teams have experienced a decline in the number of
      direct operations performed for life-threatening ventricular tachycardia. This is
      probably due to the widespread use of thrombolytic therapy during the acute phase
      of infarct formation. But also to the advent of implantable cardioverter
      defibrillators that are increasingly sophisticated, easy to use and effective.
      Their increased use over the past few years is related to the belief that direct
      operations for the eradication of ventricular tachycardia foci bear a high
      operative mortality rate. However, today the operative mortality is less than 5%,
      and long term survival is up to 85% at 5 years with an extremely low incidence of
      ventricular tachycardia recurrence and sudden death. We report the results
      obtained in our first 100 patients in whom ventricular tachycardia surgical
      ablation was guided by computerized mapping of both the endocardium and
      epicardium. A particular type of ventricular tachycardia activation pattern was
      found to be associated with a higher rate of electrical failure due to a deep
      septal substratum. Appropriate management of this condition may further decrease
      the rate of ventricular tachycardia reinducibility and long term return of
      ventricular tachycardia to a level yet unachieved by any other therapeutic
      modality. The results of catheter ablation are promising, but access to
      intramural substrates remains unresolved. In patients with sustained monomorphic
      ventricular tachycardia associated with a discrete akinetic area of the left
      ventricle, surgery offered as a last resort is less likely to produce favourable
      results and the decision of its use should therefore be taken early before
      unjustified drug trials go on.

PMID- 8734173
TI  - Surgery for supraventricular tachycardia.
AB  - 1995 is the fifth anniversary of the advent of catheter ablation for the
      treatment of supraventricular tachycardia. Surgery has established the principles
      of the interventional approaches: 1) identification of the mechanism; 2)
      localization of the site of the mechanism; 3) identification of the anatomical
      arrhythmogenic substrate and its localization using preoperative and
      intraoperative electrophysiological cardiac mapping; 4) ablation of the
      arrhythmogenic substrate using "surgical" dissection or excision or various forms
      of energy to neutralize the substrate: cryoablation, laser, etc. Surgical
      approaches also established the EP interventions as the first line of therapy
      because they are curative. Currently, surgery for supraventricular tachycardia is
      essentially confined to atrial fibrillation, and after attempted catheter
      ablation for the Wolff-Parkinson-White syndrome. Atrial fibrillation is a complex
      arrhythmia, commonly associated with structural heart disease. To understand
      atrial fibrillation, a number of premises should be reviewed: atrial functional
      anatomy, atrial pathology, atrial fibrillation mechanism (s) and clinical
      presentation. The role of atrial fibrillation in terms of symptoms, morbidity and
      mortality is not clear because it is difficult to determine if atrial
      fibrillation is a symptom, a marker, an autonomous disease albeit it is in most
      cases an aggravating factor. Surgical rationales for atrial fibrillation are
      based on three concepts: exclusion, fragmentation and channelling. The Corridor
      operation was the first used direct surgical approach. The Maze operation and
      other techniques (fragmentation, spiral) have been reported. All surgical
      techniques have been reported with good results in terms of sinus node function
      and exercise tolerance, and to various degrees, in terms of atrial contraction.
      Currently, there is a trend to combine direct atrial fibrillation surgery with
      surgery for mitral valve albeit beneficial effects are not documented.

PMID- 8734174
TI  - The implantable cardioverter defibrillator: modern implantation techniques and
      their impact on outcomes.
AB  - The implantable cardioverter defibrillator has revolutionized the management of
      lethal ventricular arrhythmias in susceptible patients. In its second decade of
      existence, the implantable cardioverter defibrillator has undergone significant
      technologic enhancements which have resulted in ease of implantation, lower
      mortality rates, and shorter hospital stays. The newer pectoral size devices have
      been successfully implanted in a variety of patients, using models from several
      device manufacturers. Improvements in lead technology have paralleled those of
      the device itself. These include the unique concept of "unipolar" defibrillation
      as well as the trend toward dual chamber lead systems. Results of these newer
      technologies are favorable: comparably low defibrillation thresholds have been
      reported with the newer lead configurations, with lower operative mortality.
      However, morbidity attached to earlier lead systems remains as high as 16%. It is
      anticipated that the results will further improve as shorter transvenous leads
      and better connector material become routinely available. Finally, the clinical
      outcomes in the early postoperative phase indicate fewer proarrhythmic effects
      leading to shorter hospital stays in patient equipped with the latest types of
      pectoral implants. Continued progress at the level of the patient-device
      interface is expected to result in every better patient acceptance and
      proliferation of implantable cardioverter defibrillator therapy.

PMID- 8734175
TI  - Comparison of burst pacing, autodecremental (ramp) pacing, and universal pacing
      for termination of ventricular tachycardia.
AB  - This study was designed to test the comparative efficacy of burst pacing,
      autodecremental (ramp) pacing, and universal (steep ramp) pacing for termination
      of ventricular tachycardia. A prospective, randomized sequence cross-over design
      was used to achieve comparisons of the pacing modalities that were matched for
      patient, day, and ventricular tachycardia characteristics. Thirty eight patients
      were enrolled, whose ventricular tachycardia was well-enough tolerated to be
      reinduced, and tested with 3 pacing modalities. There were 27 series 1 patients
      in which the pacing modalities were nonsynchronized burst pacing, synchronized
      burst pacing, and ramp pacing. The 11 patients in series 2 were tested with
      synchronized burst pacing, ramp pacing, and universal pacing. All pacing methods
      proved to be comparable in their ability to terminate ventricular tachycardia (p
      = NS). The 2 burst methods required the fewest number of attempts (significant vs
      ramp pacing). Universal pacing required the fewest number of stimuli. The mean
      paced cycle length was similar will all methods. The shortest paced cycle lengths
      were found with the autodecremental and universal methods because of their ramp
      patterns. It is concluded that burst, ramp, and universal pacing are of similar
      efficacy, although ramps were least efficient. Choice of a modality depends on
      operator preference, and individual patient response.

PMID- 8734176
TI  - Implantable cardioverter-defibrillator: present and future indications.
AB  - Indications for of automatic cardioverter-defibrillators of automatic in patients
      with ventricular tachyarrhythmias have changed since the publications of first
      guidelines in 1991. Less invasive surgical approaches reduced the perioperative
      mortality. Tiered therapy devices improved the quality of life by reducing
      appropriate and inappropriate shocks. A low annual incidence of sudden death with
      implantable cardioverter defibrillators and frustrating results with
      antiarrhythmic drugs caused an extension of implantable cardioverter
      defibrillator indications. Despite the absence of prospective studies implantable
      cardioverter-defibrillators have become a first line treatment for patients with
      ventricular tachyarrhythmias which are not due to acute myocardial infarction. In
      cardiac arrest survivors implantable cardioverter-defibrillator therapy has
      become the gold standard due to the low annual incidence of sudden death seen in
      implantable cardioverter-defibrillator patients. The results of ongoing
      prospective studies comparing implantable cardioverter-defibrillator therapy to
      antiarrhythmic drugs have to be awaited and will influence tomorrow's indications
      for implantable cardioverter-defibrillator therapy in patients with documented
      ventricular tachyarrhythmias. Additionally, studies evaluating prophylactic
      implantable cardioverter-defibrillator implantations in patients at high risk for
      ventricular tachyarrhythmias might expand indications for implantable
      cardioverter-defibrillator therapy.

PMID- 8734177
TI  - New generations of implantable pacemaker defibrillators for ventricular and
      atrial tachyarrhythmias.
AB  - Implantable defibrillation devices have now been extensively applied to patients
      requiring cardioversion and defibrillation of sustained ventricular
      tachyarrhythmias. The focus of new developments is in improving technology,
      achieving physiologic operation in the atrium and ventricle, seeking new
      indications and identifying patient populations amenable to this therapy.
      Ventricular application technology is focusing on simplifying and improving
      robustness of lead systems yet seeking lower defibrillation thresholds. Dual
      chamber pacing, sensing and defibrillation are being developed. New populations
      for ventricular application include non-sustained ventricular tachycardia
      patients with coronary artery disease, dilated cardiomyopathy at risk for sudden
      death, long QT syndrome, pediatric patients with risk of sudden death and high
      risk postoperative coronary bypass patients. New applications include atrial
      defibrillation combined with atrial pacing in future devices. These devices are
      planned to have capabilities of ventricular defibrillation as a backup to address
      proarrhythmia concerns. It can be anticipated that implantable cardioverter
      defibrillator devices will be used for arrhythmia reversion in an expanding group
      of patients in the future.

PMID- 8734178
TI  - [Treatment of acute myocardial infarction. (STIM 93 registry)].

PMID- 8734179
TI  - [Therapeutic strategies in acute myocardial infarction. Results of STIM 93
      registry].
AB  - A registry was set up by the national college of cardiologists practicing in
      general hospitals in February 1993. The data concerned mode of admission,
      demographic details, initial clinical and haemodynamic evaluation and hospital
      outcome. Special attention was given to the electrocardiographic changes before
      and, in patients receiving thrombolytic therapy, after treatment. An analysis of
      predictive factors for mortality was performed both in the group of patients
      "revascularised" and in the group treated conventionally. One thousand and twenty
      three cases from 327 centres were analysed. There were 1292 men and 531 women,
      with an average age of 67.9 years. The average time interval from onset of
      symptoms to hospital admission was 5 h 30 min, 56.8% of patients arriving within
      6 hours. 36.4% of the population underwent thrombolysis or angioplasty, 75% of
      patients under 75 years of age admitted before the 5th hours underwent a
      procedure of myocardial revascularisation. The hospital mortality was 14%, 8.7%
      in those revascularised and 17% in patients treated conventionally. Factors
      predictive of mortality were age, female gender, Killip Classes III or IV,
      systolic blood pressure of less than 100 mmHg, heart rate of more than 100/min
      and contraindications of thrombolysis. The maximum ST depression, the sum of ST
      depression, the sum of ST elevation and depression, were also significant
      predictive factors of a fatal hospital outcome in the whole population group and
      in patients treated conventionally. In the reperfused group, only the initial sum
      of ST elevation and depression was predictive of mortality: 120 minutes after the
      beginning of thrombolysis, the sum of ST elevations and of elevations and
      depressions was predictive of twice the mortality when the values exceeded 0.6 mv
      and 1.4 mv respectively.

PMID- 8734181
TI  - [Can signal-averaged electrocardiograms be interpreted in cases of complete
      bundle branch block?].
AB  - The aim of this study was to evaluate the results of signal-averaged (SA) ECG in
      cases of complete right (RBBB) or left bundle branch block (LBBB). One hundred
      and seven patients had RBBB; 42 without cardiac disease (0), 56 with chronic
      myocardial infarction (MI) and 9 with primary cardiomyopathy (CMP). Seventy-four
      patients had LBBB: 20 without cardiac disease, 26 with chronic myocardial
      infarction and 28 with primary cardiomyopathy. A SA ECG (Cardionics, Fidelity)
      was performed with a 40 Hz band pass and compared with the recordings of 72
      healthy controls without bundle branch block. The duration of the averaged QRS
      (QRS dur), the voltage of the last 40 milliseconds (RMS40) and duration of
      terminal activity < 40 microV (LAS) were measured. The analysis of results showed
      that QRS dur was significantly longer in subjects with ventricular tachycardia
      (VT) (p < 0.05) and in those with advanced cardiac disease (p < 0.05), whatever
      the type of bundle branch block, and that only the RMS40 distinguished patients
      with VT from those without VT, irrespective of the underlying cardiac disease and
      the type of bundle branch block. However, the study of the diagnostic value of
      each parameter showed very mediocre results: RMS 40 < 20 microV in myocardial
      infarction and < 17 microV in cardiomyopathy had sensitivities and specificities
      in RBBB of 73% and 50% respectively, incalculable in CMP, in LBBB 70% and 33%,
      77% and 60% respectively; the LAS was unusable. The authors conclude that it is
      hazardous to interprete SA ECG in bundle branch block, especially in advanced
      cardiac disease where the specificity of the criteria becomes very low (< 50%).

PMID- 8734180
TI  - [Coronary artery stenting without antivitamin K. Results after a month].
AB  - This paper reports experience with a new antithrombotic agent prescribed to
      reduce the incidence of subacute occlusions during the first month after coronary
      stenting. Therefore, a powerful association of platelet antiaggregant agents was
      tested. From December 1992 to October 1994, coronary stenting was successfully
      achieved in 1,294 patients (1,118 men, average age 60.5 +/- 10 years) who were
      then treated with the association of ticlopidine 0.25 g/day and aspirin 0.10
      g/day for one month. This was covered with anticoagulation with a low molecular
      weight heparin for a variable period (one month, two weeks, then one week),
      according to the different phases of the study protocol. In all, 1487 stents were
      successfully implanted (1,330 Palmaz Schatz; 63 Cook; 80 Wictor; 13 AVE and 1
      Strecker) in 1,326 vessels (520 left anterior descending, 208 left circumflex,
      475 right coronary, 16 left main coronary arteries and 107 venous grafts) using
      balloon catheters of 2.5 mm to 5 mm diameter for average 3.45 +/- 0.4 mm). Major
      complications in the first month included 9 deaths (0.7%), 22 occlusions (1.7%):
      14 myocardial infarcts (1%) and 11 aorto-coronary bypass procedures (0.85%).
      There were 136 local haematomas or false aneurysms (10.5%), 42 of which (3.25%)
      required blood transfusion or surgical repair. This multicenter trial of a
      protocol associating platelet antiaggregant agents and low molecular weight
      heparin for one month showed a low incidence of subocclusion after coronary
      stenting (1.7 +/= 2.5%) and should enable interventional cardiologists to widen
      the indications for coronary stenting.

PMID- 8734182
TI  - [Tolerance of amlodipine in left ventricular dysfunction of ischemic origin].
AB  - The aim of this study was to assess the effects of amlodipine on left ventricular
      function at rest and on effort, at least 30 days after myocardial infarction. The
      30 patients included in the study had resting isotopic ejection fractions of 40
      to 60%. At inclusion and after 15 days treatment with 10 mg of amlodipine, the
      patients underwent exercise stress testing with a standard Bruce protocol and
      resting and exercise isotopic left ventricular ejection fractions were measured.
      The association of betablockers was allowed but vasodilator therapy was
      prohibited. During the second exercise stress test, the duration of exercise
      increased (437 +/- 167 to 518 +/- 154 s; p < 0.002) and the work level rose from
      140 +/- 56 to 169 +/- 60 Watts; p < 0.04. The number of electrically positive
      tests did not change significantly (33 vs 26.7%; NS). The resting ejection
      fraction did not increase after 15 days treatment with amlodipine (47.4 +/- 6.7
      vs 48.3 +/- 8.9%; NS). Similar results were observed with respect to the exercise
      ejection fraction (51.4 +/- 10.4 vs 52.6 +/- 8.6%; NS). These patients may
      however be divided into two subgroups. In the first subgroup of 10 patients, the
      resting ejection fraction rose by more than 5% with amlodipine whereas the
      exercise ejection fraction remained unchanged (54.4 +/- 7.7% vs 54.5 +/- 7.5%
      with amlodipine). In the second subgroup of 20 patients, the resting ejection
      fraction decreased slightly with amlodipine (48 +/- 6.9% vs 45.3 +/- 8%; p =
      0.04) but increased significantly on exercise (45.3 +/- 8% vs 51.7 +/- 9.1%; p <
      0.0002). Therefore, amlodipine, a new generation calcium antagonist, does not
      induce any deleterious effect after myocardial infarction with mild left
      ventricular dysfunction.

PMID- 8734183
TI  - [Thrombosis from mechanical valve prostheses in the Reunion island].
AB  - Between October 1991 and January 1995, 10 patients presented 14 episodes of
      thrombosis of mechanical valve prosthesis, 11 obstructive, 3 nonobstructive. In
      two cases, the thrombosis was recurrent (one after thrombolysis, one after
      surgical thrombectomy). In another two cases, the thrombosis was a recurrence (on
      a valve already surgically replaced because of thrombosis). Anticoagulant therapy
      had been ineffective in 9 cases; protein S deficiency was diagnosed in one case.
      Transoesophageal echography allowed diagnoses in all cases. Thrombolysis was the
      treatment of first intention in 9 cases (completed by a second course of
      thrombolysis in one case and by valvular replacement in two cases. The other
      patients were managed by immediate valve replacement in two cases, thrombectomy
      in one case, long-term parenteral anticoagulation in two cases (one of which was
      followed by valve replacement). Transoesophageal echography showed improved valve
      motion. Incomplete thrombus dissolution was observed in 50% of cases.
      Thrombolytic therapy was complicated by cerebrovascular accidents in two
      patients, one of which was fatal. One patient had regressive hemiplegia, one
      patient had a local hematoma. The authors conclude that thrombosis is a serious
      complication of valve replacement and usually occurs in patients inadequately
      anticoagulated. Thrombolysis may enable some patients to avoid reoperation but
      its risks limits its use to those patients thought to be unacceptable surgical
      risks. An apparently high frequency of this complication durind this period has
      led to the initiation of a study to determine the predisposing factors and to put
      preventive measures into action.

PMID- 8734184
TI  - [Mid-term outcome of escape rhythm after radiofrequency ablation of the
      atrioventricular junction].
AB  - Mid-term outcome of the underlying escape rhythm developed after radiofrequency
      ablation of the atrio-ventricular junction was studied in 50 consecutive patients
      (28 women and 22 men with a mean age of 66.2 +/- 9.6 years). The escape rhythm
      was assessed immediately after ablation and after 13.7 +/- 8 months. At the end
      of ablation: an escape rhythm was present in 38 patients (76%), with a mean rate
      of 40.7 +/- 9.7 beats/min and a QRS morphology identical to the preablation QRS
      morphology in 22 patients (58%). At follow-up: an escape rhythm was present in 37
      patients (74%), with a slower mean rate of 36.4 +/- 6.8 beats/min (p < 0.05) and
      an unchanged QRS morphology in 87.5% of the patients. Patients presenting with an
      escape rhythm at follow-up were more frequently found to have a postablation
      escape rhythm (p < 0.01). Escape rhythm presence at follow-up was not influenced
      by age, presence of a cardiac disease, continuation of an antiarrhythmic
      treatment after ablation, use of a bilateral approach for ablation or number of
      radiofrequency applications. CONCLUSION: after abrupt inhibition of the
      stimulation, an escape rhythm was present only in 74% of the patients 13.7 +/- 8
      months after atrio-ventricular junction radiofrequency ablation. QRS morphology
      was identical to the preablation morphology in 57% of the patients.

PMID- 8734185
TI  - [Reproducibility of signal-averaged electrocardiography].
AB  - The reproducibility of the parameters defining the presence of late potentials on
      the signal-averaged electrocardiogram is one of the limiting factors of the
      method. The authors studied the coefficients of correlation and reproducibility
      of these parameters in patients with coronary artery disease. In addition, they
      tried to determine which parameter was most often responsible for changing a
      diagnostic conclusion (i.e., presence or absence of late potentials). Two signal
      averaged ECGs were recorded one after the other in 127 patients. The presence of
      late potentials was defined as the presence of a least two of the following
      criteria: total amplified and averaged QRS duration (tQRS) > 114 ms: duration of
      the last signal of under 40 microV (LAS) > 38 ms, and root mean square of the
      amplitude of the last 40 ms (RMS) < 20 microV. The correlation coefficients were
      0.98, 0.96 and 0.94 for the duration of tQRS, LAS and RMS respectively (p <
      0.0001). The coefficients of reproducibility were 7.0 ms. 7.0 ms and 16.1 microV
      respectively. Late potentials were present in 22% of patients. A change in
      diagnosis between the first and second recording was observed in 10 subjects (8%
      of the population). A combined change in LAS and RMS was responsible for 6 of
      these revised diagnoses, a change in LAS alone in 2 cases, of the RMS alone in 1
      case and the tQRS alone in 1 case. In patients with coronary artery disease, the
      immediate reproducibility of the diagnosis of late potentials is affected by
      changes in LAS and RMS. The tQRS is only rarely responsible for a change in
      diagnosis. This study suggests that the result of the signal-averaged ECG should
      be interpreted with caution when the LAS or RMS are near their threshold values.

PMID- 8734186
TI  - [Reoperation for aortic valve replacement after myocardial revascularization].
AB  - A series of 13 patients (11 male, 2 female, average age 61 +/- 6 years) with
      previous aortocoronary bypass surgery and reoperated for aortic valve replacement
      (AVR) were analysed retrospectively. At coronary bypass, 8 patients (Group I) has
      insignificant aortic stenosis (AS) (mean transvalvular pressure gradient < 40
      mmHg and/or aortic valve surface > 1 cm2). The other 5 had no aortic valvular
      lesion (Group II). The average time interval between the two operations was 7 +/-
      3.3 years (Group I: 6.7 +/- 3.5 years; Group II: 7.4 +/- 3.2 years). In Group I,
      2 patients required early AVR (2 years) whereas the time of reoperation varied
      from 6 to 12 years in the other 6 patients. No operative complications related to
      the sternotomy or dissection of adhesions were observed. In 3 cases, it was
      necessary to free the implanted grafts on the right coronary artery to gain
      access to the initial part of the aorta. A transverse low aortotomy allowed AVR
      in good conditions in all cases. One patient in Group II died on the 5th
      postoperative day of a low output syndrome complicated by pneumonia. After an
      average follow-up of 3 +/- 2 years, 9 patients are still alive. Three patients in
      Group I died, two of cardiac failure and one of unknown causes. The authors
      conclude that "prophylactic" AVR in cases of insignificant AS in patients
      referred for coronary bypass surgery is not justified. Regular echocardiographic
      follow-up should lead to AVR at the most appropriate moment, sometimes after an
      interval of several years, with a low operative risk.

PMID- 8734187
TI  - [Attitudes of French cardiologists towards smoking].
AB  - The object of this study was to evaluate the attitudes and opinions of French
      cardiologists towards smoking. A postal enquiry was performed with the aid of the
      French Society of Cardiology and the French Federation of Cardiology in 1993
      using a questionnaire developed by the World Health Organisation and the
      International Union against Tuberculosis and Respiratory Diseases (IUATRD). Seven
      hundred and thirty cardiologists replied (34% of the study population). The
      average age was 47 +/- 9 years; 84% were male. The prevalence of smoking was 27%
      (14% daily smokers and 13% occasional smokers); 47% were former smokers and 26%
      had never smoked. The proportion of physicians who had never smoked was higher in
      the younger age groups (29 to 45 years) than in the older age groups (33% versus
      21% in the over 45). Forty-two per cent of daily smokers had tried seriously to
      stop smoking at least once but only 16% hoped to stop smoking in the following 5
      years. Young cardiologists were more aware of the cardiovascular and respiratory
      diseases related to tobacco consumption. Only 64% of cardiologists (54% of daily
      smokers) systematically warned a smoker if the patient had no tobacco-related
      illness or did not ask about smoking systematically. Forty-seven per cent of
      those who replied stated that they were underinformed about the methods of
      helping patients to stop smoking. The authors conclude that fewer French
      cardiologists smoke than their general practitioner counterparts (14% of daily
      smokers versus 21%). They have a better understanding of the respiratory and
      cardiovascular risks of tobacco consumption but seem to be insufficiently
      prepared to help their patients to stop smoking. In addition, their personal
      behaviour with regards to smoking influences their attitude towards patients who
      smoke.

PMID- 8734188
TI  - [Arrhythmia after surgery for congenital cardiopathies. What studies? What
      treatment?].
AB  - Cardiac surgery has greatly improved the outlook for patients with heart defects,
      giving them a much longer lifespan; it has also created specific problems and
      morbidity, amongst which arrhythmias are most prominent. The incidence of rhythm
      disturbances increases with age and duration of follow-up. To a large extent, the
      type of surgery determines the type of arrhythmias: conduction disturbances and
      ventricular arrhythmias are common after ventricular surgery (e.g. tetralogy of
      Fallot) whereas sinus node dysfunction, with its bradycardias and tachycardias,
      is prominent after atrial surgery (e.g. Mustard or Senning operations). Various
      types of investigations, both non invasive (Holter, exercise testing, signal
      averaging) and invasive electrophysiology) are available. The usefulness of these
      different techniques for each type of rhythm disturbance is discussed. Regarding
      treatment, abstention is the best approach in many cases. Others however require
      treatment to suppress symptoms and, sometimes, to try and prevent sudden death.
      The indication for various antiarrhythmic medications and also for pacemaker
      implantation are discussed. Radio frequency ablation appears to hold some promise
      for the future.

PMID- 8734189
TI  - [Mechanisms of restenosis after coronary angioplasty].
AB  - Coronary restenosis is the direct result of arterial trauma caused by angioplasty
      and therefore affects all patients to different degrees. Fracture of the plaque
      extending to the media is the principal mechanism of increase of the arterial
      lumen after balloon angioplasty, wall stretching concerning mainly excentric
      lesions. Atherectomy causes pulverisation of excision of the plaque without
      fracture. Stents reduce the amount of debris and the torn appearances of the
      plaque often observed after angioplasty. Four mechanisms are involved in the
      induction of restenosis: neointimal hyperplasia, proportional to the amount of
      trauma (damage to the internal elastic layer), related to proliferation of smooth
      muscle cells migrating from the media to the intima nad stimulated by many growth
      factors: defective remodelling or chronic elastic recoil, characterised by a
      reduction of the arterial lumen at the angioplasty site; acute elastic recoil in
      the first minutes or hours after angioplasty, mainly observed in excentric
      lesions; thrombosis, whose role is secondary except in certain clinical
      situations such as unstable angina, angioplasty of saphenous vein grafts or long
      dissections. The classical theories of restensosis attribute a major role to
      initial hyperplasia but more recent experimental and clinical data, obtained
      largely from endocoronary ultrasonography, suggest that defective remodelling may
      be more important. Although endocoronary stents prevent acute and chronic elastic
      recoil effectively, they do not prevent restenosis which remains a complex,
      multifactorial phenomenon.

PMID- 8734190
TI  - [Intrathoracic textiloma after cardiac surgery. Apropos of a case].
AB  - The authors report an exceptionally rare case of intrathoracic textiloma
      presenting with a recurrence of chest pain after myocardial revascularisation by
      double internal mammary artery bypass grafting. The diagnosis was suspected
      before reoperation from the results of echocardiography. CT scanning and magnetic
      resonance imaging. The authors discuss the clinical and paraclinical features and
      the treatment. The medico-legal aspects of this surgical complication are not
      negligeable.

PMID- 8734191
TI  - [Isolated anomalous origin of a septal artery from a third coronary ostium.
      Apropos of a case].
AB  - The authors report the case of a patient undergoing coronary angiography for
      angina who had an anomalous origin of the septal perforator artery from a
      separate ostium. Anomalies of the coronary arteries may consist not only of
      anomalous trajectories and coronary fistulae but also of anomalous origins of the
      main coronary arteries. The anomalous origin of a septal artery from a separate
      ostium is very rare accounting for 0.5% of cases in the medical literature. In
      some cases, this artery provides a collateral circulation for occluded main
      coronary vessels, thereby preserving left ventricular contractility.

PMID- 8734192
TI  - [Pulmonary embolism and thrombus trapped in a patent foramen ovale. Cure by
      heparin therapy].
AB  - The authors report the case of a 84-year old patient admitted to hospital for
      pulmonary embolism. The diagnosis was made by ventilation and perfusion pulmonary
      scintigraphy. Transthoracic echocardiography was performed routinely and showed a
      thrombus wedged across a patient foramen ovale, confirmed at transoesophageal
      echocardiography. Spiral thoracic computerised tomography showed thrombus in the
      two main pulmonary arteries and the inferior vena cava. Thrombolysis or
      thrombectomy under cardiopulmonary bypass, was thought to carry an excessive risk
      at that age and with the left-sided position of the thrombus. The alternative was
      therefore anticoagulation which led to dissolution of the thrombus without
      recurrence of pulmonary embolism or cerebrovascular accident.

PMID- 8734193
TI  - [Complete regression of cardiac non-Hodgkin's lymphoma after 23 months with
      chemotherapy].
AB  - The authors report the case of a non-Hodgkin malignant lymphoma (NHL) of the
      heart presenting with syncope. The diagnosis of a cardiac tumours was made by
      echocardiography. Myocardial biopsy enabled diagnosis of a highly malignant NHL
      in a patient with a history of low grade NHL. Chemotherapy with CNOP
      (Cyclophosphamide, Novantrone, Oncovin, Prednisone) induced total regression of
      the tumour. The patient is in total remission 23 months later. The authors
      emphasise the value of echocardiography in the diagnosis and follow-up of this
      pathology. The case is also noteworthy because of the unusual transformation of a
      low grade to a high grade cardiac NHL.

PMID- 8734194
TI  - [Laparoscopic colectomy: technique and results].
AB  - Laparoscopic preparation before colectomy consists of freeing the colon
      laparoscopically followed by a small elective laparotomy for resection and
      anastomosis. From January 1993 to October 1994, we performed 86 consecutive
      planned colectomies including 16 (19%) which had laparoscopic preparation. In 3
      of these cases (19%) the procedure was converted to laparotomy due to difficult
      dissection. The 13 patients with complete laparoscopically prepared colectomy
      were retained for this study. There were 9 men and 4 women, mean age 54 +/- 14
      years (range 34-79). Indications for surgery were benign tumor (n = 4),
      metastatic cancer (n = 3), diverticulosis (n = 3), volvulus of the pelvic colon
      (n = 2), and endometriosis involving the sigmoid (n = 1). Operative procedures
      were: short segmentary colectomy (n = 6), sigmoidectomy (n = 5), right colectomy
      (n = 2). Surgery duration was 280 +/- 75 minutes (range 150-390). The post
      operative period was uneventful in all patients. Bowel activity resumed on the
      second day after surgery in most patients. Mean hospitalization time was 7.4 +/-
      1.4 days (range 5-10 days). Laparoscopically prepared colectomy is a reliable
      simple method providing good patient comfort post-operatively. This technique
      should find its place in surgery of the colon.

PMID- 8734195
TI  - [Adrenalectomy by posterior approach for benign adrenocortical tumors. Apropos of
      12 cases].
AB  - The posterior extra-peritoneal route is usually preferred for exeresis of benign
      tumors of the adrenal glands measuring less than 5 cm. We examined the hospital
      reports for patients in which Young access was used since 1985. From December
      1985 to December 1994, 12 patients underwent surgery for benign tumor of the
      adrenal gland. There were 9 women and 3 men (mean age 49.4 years, range 29-67).
      In all patients, the tumor was localized pre-operatively on a CT-scan. There was
      a unique tumor in each case. There were 11 adrenal adenomas including 10 Conn
      tumors and 1 secreting tumor (Cushing's syndrome). The last case was a cortical
      cyst. One patient died in the post-operative period, probably due to massive
      pulmonary embolism although necroscopic evidence was not obtained. Parietal
      infection occurred in one case and a spontaneously regressive hematoma in
      another. Mean duration of hospitalization was 7.0 days. At follow-up, 1 patient
      suffered deinnervation of the oblique muscles of the abdomen which did not
      require reoperation. Two months after surgery, clinical signs and hormone
      disorders related to the Conn adenomas had regressed in 7 of the 9 patients. In
      summary, the posterior route is perfectly adapted to the treatment of benign
      tumors of the adrenal glands when the exact localization can be identified on pre
      operative imaging. This access should be considered as the reference route of
      evaluating laparoscopic procedures.

PMID- 8734196
TI  - [Management of patients with pain in the right iliac fossa and human
      immunodeficiency virus infection].
AB  - Pain in the right iliac fossa in a patient infected with HIV raises several
      questions which can mislead or delay diagnosis leading to increased morbidity and
      mortality. We report 3 cases selected because of the difficulties encountered in
      diagnosis or treatment and review the literature on the topic in an attempt to
      develop a management strategy for such patients.

PMID- 8734197
TI  - [Total rectal prolapse in children. Diagnostic and therapeutic trends. Statistics
      apropos of 52 cases].
AB  - Rectal procidentia represents classically only 2% of rectal prolapse in children.
      This rarity is more apparent than real, because peritoneographies showing the
      excess of migration of the rectogenital pouch, allows to diagnose more often this
      pathology. The normal trend of this anomaly of the infant and the young child
      even if it could be serious with strangulation is usually a spontaneous healing.
      Accordingly therapeutic indications should be cautious. Surgery is only indicated
      in confirmed or complicated forms. After analysis of the statistic of 52
      observations, the modified Lockhart-Mummery is our prefered procedure. It needs a
      short and simple surgery and the results appear satisfactory.

PMID- 8734198
TI  - [Primary acute osteomyelitis of the sternum associated with anterior
      mediastinitis].
AB  - In a 14-year-old adolescent, primary acute osteomyelitis in a rare localization,
      the sternum, was associated with anterior mediastinitis. Antibiotic therapy and
      partial sternectomy together with emptying the mediastinal abscess was
      successful. Therapeutic management of such cases is presented in a review of the
      literature.

PMID- 8734199
TI  - [Local treatments of rectal cancer].

PMID- 8734200
TI  - [Percutaneous resection of osteoid osteoma].
AB  - Therapeutic management of osteoid osteomas may vary from conservative medical
      treatment to more aggressive, though effective, surgery. Based on observations in
      4 cases in children, we demonstrate the importance of localizing the lesion on
      the CT-scan before percutaneous resection of the osteoid osteoma involving small
      bones since this method is the most conservative surgical procedure.

PMID- 8734201
TI  - [The millepede and the surgeon. Apropos of laparoscopic cholecystectomy in a case
      of situs inversus or automatic gesture constricted by reason].

PMID- 8734202
TI  - [A new case of diverticular sigmoido-cervical fistula].

PMID- 8734203
TI  - [Mesenteric infarction: resection and second-look surgery].

PMID- 8734204
TI  - [Treatment of post-coronarography femoral false aneurysm by compression, guided
      by Doppler echography].
AB  - MATERIAL AND METHODS: We evaluated the role of color Doppler US-guided
      compression in the non-invasive treatment of femoral artery pseudoaneurysms after
      cardiac catheterization, including 22 PTCA procedures. The diagnosis of 32
      pseudoaneurysms in 32 patients was accomplished by detection of the typical US
      Doppler pattern consisting of the swirling color Doppler flow and the "to and
      fro" pulsed Doppler waveform at a mean 3.6 days (1 to 14) after the cardiac
      catheterization. Thirteen patients had multiple cavity pseudoaneurysms (2 to 4).
      All the patients immediately underwent compression therapy. RESULTS: Treatment
      was successful in 42/49 cavities (86%) and 25/32 patients (78%), usually after 1
      to 3 compression cycles of 6 to 8 minutes duration. Only one recurrence was noted
      at the 24 hour US-Doppler follow-up. In all cases, pain relief during compression
      was an excellent clinical sign of hemostatic plug formation and conversion from
      pseudoaneurysm to simple hematoma. Failures occurred among patients under high
      dose anticoagulants in spite of 4 to 10 compression cycles. COMMENTARY: In
      conclusion, color Doppler US-guided compression of post-cardiac catheterization
      pseudoaneurysms should be the first line therapeutic modality, even in cases of
      multiple cavities and among patients under effective anticoagulation therapy.

PMID- 8734205
TI  - [Ano-perineal fistula in MRI. Contribution of T2 weighted sequences].
AB  - INTRODUCTION: Anal fistulae are pathological conditions observed in infections of
      the Hermann and Defosses' glands or related to Crohn's diseases. The success and
      the lack of complication of surgical treatment depends on how accurately the
      tracks are assessed. The contribution of MRI in anal fistulas is now well
      established but the imaging appearance is not well discribed. The purpose of this
      work was to discribe the different patterns of lesions. MATERIAL AND METHODS:
      Eighteen patients with anal fistulas were examined with MRI before operation
      (mean delay: 14 days. range: 1-56). SE T2 sequences, in coronal and axial planes
      referred to the anal canal were performed. The examinations were reviewed and
      compared with the results of surgical assessment to correlate imaging and
      surgical findings. RESULTS: Lesions were hyperintense on T2-weighted sequences
      but were also iso- or poorly hyper-intense when they did not contain fluids but
      only inflammatory tissue. When involving the supra-levator space, lesions were
      nodular. They were well limited if they occurred in the supra-levator space
      itself. On the contrary, the rectal wall was thickened and hyper-intense when the
      fistulous tract reached it. Lesions were similar in Crohn's disease, except for
      anal fissures which were seen as a tubular hypersignal in contact with the anal
      lumen. On T2 sequences, healed fistulas were not visible. CONCLUSION: The simple
      SE T2 sequences can discriminate between different patterns of lesions,
      especially for supra-levator extensions, fissures in Crohn's disease and chronic
      inflammatory lesions without fluid. The use of more recent machines or fat
      suppression sequences may improve the detectability of lesions, especially the
      more chronic ones.

PMID- 8734206
TI  - [Structural MRI study of the Achilles tendon. Correlation with microanatomy and
      histology].
AB  - On T1 and T2 weighted MR Imaging, normal Achilles tendon is generally described
      as a homogeneous low signal structure. However, punctuate and/or short linear
      high signal foci are often seen, especially on the anterior part of axial
      sections. These images are not artifacts. The aim of this study was to correlate
      MR images of 20 normal Achilles tendons with micro-anatomic and histologic
      studies of 2 cadaver tendons. Intratendinous vessels were found in connective
      tissue septa called mesotenon. Foci of high signals result from this mesotenon.
      On T1 weighted images, a normal Achilles tendon can present high signal images
      without any disease process.

PMID- 8734207
TI  - [Hypoplasia of the inferior vena cava with intrahepatic continuation. Color
      Doppler ultrasonography and MRI].
AB  - We report a rare case of inferior vena cava hypoplasia discovered fortuitously,
      with intra-hepatic venous shunts, explored only by color-doppler ultrasound and
      MRI. These noninvasive imaging tests demonstrated that the intra hepatic
      collateral pathway arose from an inferior (accessory) right hepatic vein and
      flowed into the right and middle hepatic veins. Due to these findings a
      cavography was avoided in this asymptomatic patient.

PMID- 8734208
TI  - [Pseudotumor form of focal acute pyelonephritis].
AB  - Two cases of focal acute pyelonephritis presenting with an unusual pseudo-tumoral
      appearance on CT are reported. The lesions exhibited a focal intra-parenchymal
      homogeneous round-shape mass without any other parenchymal or perirenal fat CT
      abnormalities. The final diagnosis of focal acute pyelonephritis was confirmed on
      following CT scans which demonstrated the total disappearance of the lesions in
      both cases. This particular appearance of acute focal pyelonephritis which
      mimicked a renal tumor should be clearly individualized in the terminology based
      on CT findings.

PMID- 8734209
TI  - [Synovial cyst involving isolated paralysis of the infraspinatus muscle.
      Ultrasonographic diagnosis and MRI].
AB  - A case of entrapment neuropathy of the inferior branch of the suprascapular nerve
      in the spinoglenoid notch is described. Ultrasonography and MRI examination
      showed a ganglion cyst in the spinoglenoid notch with an extension to the
      glenohumeral joint. The lesion was confirmed by surgical and pathological
      examination.

PMID- 8734210
TI  - [Colonic lumbar hernia secondary to congenital bone anomalies in a case of
      neurofibromatosis type I].
AB  - We report here a case of an asymptomatic lumbar hernia through a congenital
      defect of the posterior abdominal wall secondary to hypoplasia of the left part
      of the neural arch of L5 and S1. The bone defect was related to the
      neurofibromatosis of the patient. Plain radiograms showed a scoliosis and the
      bone defect. CT scan confirmed the osseous abnormalities and demonstrated a left
      colonic herniation through the bone defect. Many cases of lumbar hernia secondary
      to weakness of the abdominal muscles or following bone defects after bone graft
      harvesting, surgery or trauma have been described. This is, to our knowledge, the
      first case report of a lumbar hernia secondary to a congenital bone defect.

PMID- 8734212
TI  - [Time and image].
AB  - In this paper, the author proposes two themes of future research: a) time is a
      sign of the image. It occupies a place in the triadic Peirce's systems presented
      here; b) time is the fourth dimension of the image even when it is not visible as
      a sign.

PMID- 8734211
TI  - [Advanced-stage ankylosing spondylitis in a subject in the 8th century].
AB  - Paleopathological study of an adult male skeleton, coming from a Hungarian
      archeological site from the 8th century, revealed lesions of the spine
      (ankylosing vertebral syndesmophytosis, costo-vertebral ankylosis, discal
      calcifications), of the sacro-iliacs (bilateral ankylosis) and several
      extraspinal changes (abnormalities of symphysis pubis, enthesopathies).
      Radiological and CT investigations confirmed the diagnosis of advanced stage
      ankylosing spondylitis.

PMID- 8734213
TI  - [Giant Meckel's diverticulum].

PMID- 8734214
TI  - [2D and 3D reconstructions after spiral x-ray computed tomographic acquisition].

PMID- 8734215
TI  - [Etiology of enucleations. Apropos of 3,246 cases].
AB  - PURPOSE: An epidemiological study of the aetiology of enucleation was conducted
      in patients seen at the Centre Hospitalier National d'Ophtalmologie des Quinze
      Vingts, Paris. The enucleated globes were systematically sent to the laboratory
      for histological examination. METHODS AND MATERIALS: Histological results of the
      cases from the register of Anatomo-Pathology section of the laboratory of the
      C.H.N.O. des Quinze-Vingts, over a 70-year period from 1925-1995 were used; 3,246
      globes were examined, that is, 32.83% of all histological examinations. RESULTS:
      In our series, malignant tumours were the most frequent cause of enucleation
      (32%), followed by trauma (18%), glaucoma (16%), atrophies-dystrophies (16%) and
      inflammatory causes (12%). Globes without histological pathology were rare
      (0.12%). The majority of ophthamic tumours with histological confirmation were
      melanomas (65.2%) in old age and retinoblastomas (32.5%) in the newborn and early
      infancy. Our results are compared with those of other authors. CONCLUSION: Great
      improvements in medicine and diagnostic techniques have taken place, these last
      decades, and with the possibilities of early diagnosis, enucleation has become
      rare as it is being replaced by conservative management.

PMID- 8734216
TI  - [Diabetes: why so many diabetic retinopathies diagnosed in the stage of
      complications?].
AB  - PURPOSE: The aim of this study is to ascertain the reasons of the late diagnosis
      of severe diabetic retinopathies. METHODS: We analysed 30 diabetic patients seen
      at the initial examination with severe diabetic retinopathies, including risk
      factors of diabetes, quality of maintenance of a metabolic balance in blood sugar
      levels and examination of the fundus. RESULTS: Sixteen diabetic patients (53%)
      had no examination of the fundus from the onset of diabetes; 100% were over
      weighted of more than 15%; 100% had no strict metabolic control of blood sugar
      levels; 90% had high blood pressure; 60% had familial diabetes. CONCLUSION: The
      prevention of late diagnosis of severe diabetic retinopathies must be based on
      the prevention of diabetes: examination and treatment of patients with high risk
      factors of diabetes. The prevention of diabetic retinopathy relies on the
      maintenance of a strict metabolic balance in blood sugar levels and required
      examination of the fundus every year.

PMID- 8734217
TI  - [Is trabeculectomy without danger in case of threatened fixation?].
AB  - PURPOSE: This study examined the impact of trabeculectomy on the central visual
      field in patients in which field loss threatens fixation. METHODS: Fifty eyes in
      45 patients demonstrating a visual field loss threat to fixation underwent
      trabeculectomy. All patients underwent visual field assessment before and within
      two months of surgery, using both the 24-2 quantitative program on the Humphrey
      Field Analyser, and the macular program which measures the threshold sensitivity
      three times per 16 points distributed in the central 5 degrees centrally at 2
      degrees intervals. For inclusion in the study, each eye had to show involvement
      of at least two contiguous points in the central macular program, with a decrease
      in sensitivity to 15 dB or less, in a quadrant corresponding to a well-defined
      visual field defect shown on program 24-2. RESULTS: The average post-operative
      follow-up was 7.1 months (+/- 5.52). Overall intraocular pressure reduction was
      40%. Visual acuity decreased on an average of half line. None of the eyes showed
      loss of fixation. The average number of points with decreased sensitivity in the
      central 5 degrees (15 dB sensitivity or less) was 6.06 points (+/- 3.36) pre
      operatively and 5.78 points (+/- 3.85) post-operatively (p = NS). Mean Defect
      (MD) was noted to decrease by 1 dB (p = 0.0295) whereas Corrected Pattern
      Standard Deviation (CPSD) and Foveal Sensitivity (FS) was essentially stable.
      CONCLUSION: Based on the study, it appears that trabeculectomy can be safely
      offered to patients for surgical reduction of intraocular pressure even in those
      cases where central fixation is threatened by loss of vision within the five
      degrees of fixation.

PMID- 8734218
TI  - [Spontaneous dissection of the internal carotid artery in ophthalmological
      milieu. Apropos of 10 cases].
AB  - PURPOSE: Spontaneous dissection of the internal carotid artery is a rare vascular
      emergency, but represents the first cause of cerebral ischaemia of young
      patients. Neuro-ophthalmologic symptoms often reveals the pathology. METHODS: Ten
      cases of spontaneous dissection of the internal artery are reported. The Claude
      Bernard Horner syndrome is the most frequent symptom typically associated with
      hemicranial headache. The headache involves the ipsilateral forequarter of the
      head and the neck. Other ophthalmologic symptoms may also reveal the carotid
      dissection. RESULTS: At first, the diagnosis is strongly suspected during Doppler
      ultrasonographic examination. During the acute phase, MRI and MRA replaces
      advantagiously arteriography, confirming this affection in a non invasive way,
      and permits investigation of associated vascular pathology like fibromuscular
      dysplasia (15% of the cases). The patients received anticoagulants in order to
      prevent thrombo-embolic complications (heparine during the acute phase relayed by
      AVK). The clinical course is usually favorable with the medical treatment.
      CONCLUSION: A painful Claude Bernard Horner syndrome strongly evokes a carotid
      dissection and the arterial check-up must be realised in emergency: at first, the
      exploratory methods associates Doppler ultrasonographic examination, MRI, and
      MRA.

PMID- 8734219
TI  - [Rapid demonstration of mutations previously identified in parents at risk of
      patients with autosomic dominant retinitis pigmentosa].
AB  - PURPOSE: We have previously identified rhodopsin gene mutations in France in
      autosomal dominant (ADRP) retinitis pigmentosa in France, using a combination of
      SSCP (single-strand conformation polymorphism) and direct sequence analysis. The
      aim of this study was to perform a more rapid tool to identify a mutation in a
      ADRP family, when this mutation has been identified for one affected member of
      this family. METHODS: We looked for a restriction site, created or abolished by a
      mutation in the rhodopsin gene. We performed in vitro DNA amplification using PCR
      (polymerase chain reaction), enzymatic digestion, and migration on agarose gel.
      RESULTS: Abnormal patterns of migration were observed for affected ADRP members.
      DISCUSSION: This technique is useful and rapid (less than 5 hours) to recognize a
      previously identified mutation. However, previous precise identification of the
      mutation in one member of the family is needed.

PMID- 8734220
TI  - [Spatial contrast sensitivity in patients with severe myopia].
AB  - PURPOSE: The purpose of this study was to assess the effects of amount of myopia,
      axial elongation staphyloma and type of optical correction on contrast
      sensitivity of high myopic subjects. METHODS: Fifty-one patients (91 eyes) were
      selected on the following qualifications: myopia > or = 8 dpt and/or axial length
      > or = 26 mm, and visual acuity > or = 0.1 recorded through spectacle lenses.
      Contrast sensitivity was measured using a "Moniteur Ophtalmologique" for all
      subjects when corrected with spectacle lenses, and thereafter on a lot of
      patients (50 eyes) wearing a contact lens. RESULTS: Contrast sensitivity obtained
      with spectacle lenses was significantly decreased over the whole spatial
      frequency range. The higher the spatial frequency was, the lower contrast
      sensitivity was. The impairment increased with the amount of myopia and axial
      length, but without positive correlation. Contrast sensitivity was significantly
      lower for only the three highest spatial frequencies measured (6.4; 12.8 and 25.6
      c/deg), when a staphyloma (n = 52) was present by comparison with results
      obtained for eyes without staphyloma (n = 39). Differences between the two
      situations (spectacle lens vs. contact lens) were not significant for eyes
      wearing daily spectacle lenses; conversely, for myopic subjects generally fitted
      with contact lenses, contrast sensitivity with contact lenses was significantly
      better than that measured with spectacles for the three highest spatial
      frequencies tested. CONCLUSION: This suggests that the decrease in contrast
      sensitivity measured in high myopia is related to defects in the optical and
      neuro-retinal systems.

PMID- 8734221
TI  - [Spontaneous and bilateral anterior luxation of the lens in a 5-year-old child].
AB  - The authors report a case of bilateral spontaneous dislocation of the lens in a
      five-year-old boy. This rare complication can be encountered in certain
      congenital abnormalities of the lens and zonule. The dislocation has been
      revealed by an acute glaucoma. The mains causes like Marfan's syndrome and
      homocystinuria were not found but due to their most severe prognosis. The patient
      must be followed carefully.

PMID- 8734222
TI  - [Non-sarcomatous bilateral exophthalmos disclosing acute myeloblastic leukemia in
      children].
AB  - The authors report a bilateral exophthalmos due to a leukemic infiltration of the
      orbital lacrimal glands during an acute myeloblastic leukemia in a ten-year-old
      boy. This rare orbital localization revealed the leukemia. It was not a
      granulocytic sarcoma. Its importance leads to the extraction of the lacrimal
      glands in order to prevent the eyes from corneal perforation.

PMID- 8734223
TI  - [Bilateral ocular blast injury after refractive surgery by 2 current techniques.
      Comparative anatomo-clinical analysis of a case].
AB  - Radial keratotomy reduces the strength of the cornea front of a trauma by blast.
      The authors present and analyze the case of a 25-year-old patient having been
      submitted to an ocular bilateral trauma by explosion. Twenty-two months earlier
      he had undergone radial keratotomy (RK) in the left eye followed 8 days later by
      photorefractive keratectomy (PKR) in the right eye for a -6,00 d. myopia RLE.
      Though the trauma by blast essentially reached the right eye, the corneal
      anatomical damages were more important in the left eye. This is according to us
      the first case report of trauma on eye subjected to PRK. We appreciate the
      clinical differences presented by each eye.

PMID- 8734224
TI  - [Endophthalmitis. 2: treatment].

PMID- 8734225
TI  - [Mooren's ulcer].

PMID- 8734226
TI  - [First- time isolation of the peste des petits ruminants (PPR) virus in Chad and
      experimental induction of the disease].
AB  - In Chad, in 1993-1994, investigation into "peste des petits ruminants" (PPR)
      outbreaks were carried out in flocks of Sahelian goats. Although in the early
      1993 outbreaks the virus had not been isolated yet, a serological prevalence
      (34%) was observed using ELISA test in 475 sera collected in the infested area.
      The virus was then isolated for the first time in Chad and typical PPR cases were
      observed in Sahelian goats, known to be little sensitive to the virus. To
      experimentally induce the disease, goats were inoculated with suspensions of
      lymph nodes or lungs, collected from sick animals. Lung suspensions induced the
      most serious symptoms. Suspensions of lungs and mesenteric lymph nodes were
      positive by agar-gel immunodiffusion test against PPR anti-serum, while
      prescapular lymph nodes remained negative. Characterization of the isolated
      virus, in particular with regard to its genomic identity, should be investigated.

PMID- 8734227
TI  - [Isolation of pathogenic Mycobacterium strains in cattle slaughtered in the
      abattoir of Bobo-Dioulasso, Burkina Faso].
AB  - The major cause of meat rejection at the slaughterhouse of Bobo-Dioulasso is
      bovine tuberculosis. The objective of this work was to confirm the postmortem
      diagnosis pronounced at the slaughterhouse using laboratory methods (direct
      examination following Ziehl-Hielsen staining and isolation of Mycobacterium
      strains following culture in a Loewenstein-Jensen medium. During the study, 39
      pathogenic Mycobacterium strains (38 Mycobacterium bovis and 1 Mycobacterium
      tuberculosis) out of 100 sampled out suspicious strains, were studied. No
      Mycobacteria typical of M. farcinogenes was found on direct examination. We were
      then able to differentiate between bovine tuberculosis and bovine farcy. The
      results confirm the well-founded decision in the slaughterhouse to discard the
      meat on the grounds of tuberculosis. The majority of cattle is located in
      villages around Bobo-Dioulasso and its is therefore highly likely that the
      disease is enzootic in the area with a fairly high level of infection in animals.

PMID- 8734229
TI  - Skin lesions in dogs, horses and calves caused by the stable fly Stomoxys
      calcitrans (L.) (Diptera: Muscidae).
AB  - Specific skin lesions caused by Stomoxys calcitrans on the feeding sites of
      different species are described. Skin lesions appeared on dogs, horses and calves
      following bites of stable flies. Necrotic dermatitis was observed in 32 dogs of
      various breeds at the tip of the ears. Exudative dermatitis appeared on the legs
      of 45 adult horses and dermatitis was diagnosed in the "hair whirlpools" on the
      backs of 18 white calves.

PMID- 8734228
TI  - [Epidemiology of gastrointestinal nematodes in small ruminants in the plateau
      areas in Togo].
AB  - Post-mortem helminthological examinations were performed in Togo on small
      ruminants of the Djallonke breed (59 sheep, 60 goats), revealing the presence of
      eight gastrointestinal nematode species which were, in decreasing prevalence
      order, Trichostrongylus sp. (T. axei and T. colubriformis) (99%), Haemonchus
      contortus (82%), Strongyloides papillosus (67%), Cooperia curticei (43%),
      Oesophagostomum columbianum (40%), Gaigeria pachyscelis (36%) and Trichuris ovis
      (4%). The average worm burden was 1,367 +/- 146 in sheep and 1,133 +/- 102 in
      goats with an adult worm population peak in August-September (sheep: 2,135 +/-
      494, goats: 2,066 +/- 270). During the dry season, Haemonchus contortus and
      Oesophagostomum columbianum populations were mainly in larval hypobiosis (L4).
      The number of eggs per gram faeces was usually high (> 3,000) and neither the
      species nor the age of the host (6 months to 3 years) played a significant role
      in helminth abundance.

PMID- 8734230
TI  - [Continuing education in anesthesiology and intensive care: an ethical
      obligation].

PMID- 8734231
TI  - [Analgesia after laparoscopic cholecystectomy by intraperitoneal administration
      of bupivacaine].
AB  - OBJECTIVES: The aims of this study were to assess the analgesic effect of the
      intraperitoneal topical administration of 0.375% bupivacaine in patients
      undergoing laparoscopic cholecystectomy and to carry out a pharmacokinetic study
      of bupivacaine administered topically by intraperitoneal route. STUDY DESIGN:
      Randomized, double-blind controlled trial. PATIENTS AND METHODS: Twenty-four
      patients of ASA physical status 1 or 2, undergoing elective laparoscopic
      cholecystectomy, were included. Anaesthesia technique was the same for all
      patients. At the end of surgery, they were randomly assigned to one of two
      groups. Patients in group bupivacaine were administered 0.375% bupivacaine, 0.6
      mL.kg-1 intraperitoneally in both subdiaphragmatic areas and the cholecystectomy
      wound, those of the control group were given the same volume of NaCl 0.9%.
      Analgesia was provided by morphine PCA. Postoperative pain, assessed on a 100 mm
      visual analogue pain scale (VAS), and administered morphine were recorded 30 min
      after extubation, and 0.5, 1, 2, 3, 6, 12, 24, 36 and 48 hours later. Blood
      samples were collected 2, 5, 15, 30, 60, 90, 120, 180, 300 and 480 min after the
      intraperitoneal administration of bupivacaine to measure bupivacaine plasma
      concentration. Statistics included Student t test and Chi square test. P < 0.05
      was considered significant. RESULTS: There was no significant difference between
      the two groups with regard to VAS scores during the first 48 postoperative hours.
      Morphine requirements (total and at each point) were also similar. Plasma
      bupivacaine concentrations reached a plateau at 10-20 min, and then decreased
      slowly. The median plasma peak concentration was 0.94 +/- 0.47 microgram.mL-1. In
      one patient toxic concentrations (> 1.6 micrograms.mL-1) during the first 60 min
      after intraperitoneal administration were obtained, while in another patient a
      concentration of 1.58 micrograms.mL-1 was reached twice. CONCLUSIONS:
      Intraperitoneal administration of 0.6 mL.kg-1 of 0.375% bupivacaine is
      ineffective in reducing postoperative pain after laparoscopic cholecystectomy.
      Furthermore these high doses of bupivacaine may result in toxic plasma
      concentrations. This technique is not safe and cannot be recommended.

PMID- 8734232
TI  - [Resistance to vecuronium in burnt patients. Influence of the burnt surface on
      the effectiveness of the dose 95].
AB  - OBJECTIVE: To assess the neuromuscular blocking effect of vecuronium in adult
      burn patients, to draw dose-response curves, to determine the ED 95 according to
      burn surface area, to analyze the time course of this pattern in order to
      recognize the development of a resistance according to the length of postinjury
      period. STUDY DESIGN: Prospective open study, extending over a 12 month period.
      PATIENTS: Sixty-three consecutive adult burn patients in an acute phase and 13
      control patients who had been thermally injured at least 500 days before their
      inclusion in the study. METHODS: Anaesthesia was achieved with thiopentone,
      fentanyl and vecuronium in patients undergoing excision and autograft surgery.
      Neuromuscular blockade was assessed by thumb adduction, measured by
      electromyography using evoked train of four responses to ulnar nerve stimulation.
      Dose-response curves were determined using the single dose method from only one
      predetermined dose of vecuronium per patient on each day of the study. Dose
      response curves were compared using linear regression and ED 95 were calculated
      from log-probit data. RESULTS: In the control group, ED 95 was 53 mg.kg-1. Before
      the 7th postinjury day, patients did not differ from controls. Between the 7th
      and the 70th postinjury day the ED 95 increased significantly. Patients with a
      burn surface area (BSA) of less than 20% had a ED 95 of 69 mg.kg-1, between 20%
      and 40% of BSA the ED 95 was 103 mg.kg-1, between 40% and 60% BSA the ED 95 was
      134 mg.kg-1 and patients with a BSA over 60% had a ED 95 at 154 mg.kg-1. The
      onset of action increased in all groups and was significantly different from
      control group. CONCLUSION: Acutely burn patients become resistant to the
      neuromuscular blocking effect of vecuronium. This resistance is related to the
      magnitude of burn injury. The mechanism of resistance is related to an increase
      in nicotonic acetylcholine receptors. In these patients, the dose of vecuronium
      must be titrated to achieve effective muscular paralysis: the correcting factor
      is 1.3 for a BSA under 20%, 1.9 for a BSA between 20 and 40%, 2.5 for a BSA
      between 40 and 60%, and 2.9 for a BSA above 60%.

PMID- 8734233
TI  - [Use of urapidil during surgery for pheochromocytoma].
AB  - OBJECTIVE: To investigate the efficacy of urapidil, administered either by
      boluses or a continuous infusion, to control hypertension during resection of
      phaeochromocytoma. STUDY DESIGN: Prospective open study. PATIENTS: Seven
      consecutive patients aged between 23 and 60 years, with a hypersecretant
      phaeochromocytoma. METHODS: Standard anaesthetic technique including thiopentone,
      opioid, muscle relaxant, nitrous oxide and isoflurane. Invasive haemodynamic
      monitoring with a Swan-Ganz catheter and radial arterial catheterization.
      Infusion of cristalloids and colloids (20 mL.kg-1.h-1). Evaluation of two
      regimens of urapidil administration following the initial injection of a bolus of
      25 mg in case of severe hypertension i.e. SAP > 180 mmHg > 1 min: a) boluses of
      25 or 50 mg of urapidil injected according to the response obtained after the
      first bolus or in case of resurgence of a new hypertensive event; b) continuous
      infusion of 150-200 mg.h-1. RESULTS: Three patients developed hypertension
      between the induction of anaesthesia and the beginning of the tumor dissection.
      One bolus of 25 or 50 mg of urapidil was efficient to control this event. During
      the dissection of the phaechromocytoma, higher doses (75-100 mg) were required to
      significantly decrease SAP and DAP values (P < 0.001). Heart rate did not change
      significantly in patients not receiving esmolol. A continuous infusion, used in
      three patients, did not prevent the occurrence of peaks in two patients,
      requiring additional doses. After the removal of the tumor, three patients
      experienced severe hypotension with decreased systemic vascular resistances and
      high cardiac output. Vasoactive drugs were injected to restore better
      haemodynamic conditions. CONCLUSION: Urapidil is useful for the management of
      hypertension during the resection of phaechromocytoma. However further
      investigations are needed to determine its role in the occurrence of prolonged
      collapse after the tumor removal.

PMID- 8734234
TI  - [Perioperative artificial nutrition in elective surgery. A descriptive study of
      practice patterns in France].
AB  - OBJECTIVE: To analyse the practice patterns of perioperative artificial nutrition
      in France before the Consensus Conference held on 16 december 1994 and to compare
      them with the recommendations produced by this Conference. STUDY DESIGN:
      Retrospective cross-sectional practice patterns study. PATIENTS: Sample of
      patients collected from general or digestive tract surgeons, including for each
      one the last two patients having had before 10 December 1994 either elective
      upper (oesophagectomy, duodenopancreatectomy) or elective lower (colectomy)
      abdominal surgery. The response rate to the 2, 150 circulated questionnaires was
      14% (309), producing a sample of 601 patients (49% with upper abdominal surgery,
      51% with lower abdominal surgery). RESULTS: The geographical distribution of
      surgeons who replied and their type of activity (private or public) was similar
      to the national pattern, however with some underrepresentation of the larger
      Paris area. The duration of pre- or postoperative artificial nutrition was bellow
      seven days in 36% of the cases, and above this delay in 64% of the cases.
      Artificial feeding rates for upper abdominal surgery, were 9 and 75%,
      respectively (duration of artificial feeding of 7 days and more being only
      considered). For lower abdominal surgery, these rates were 5 and 41%,
      respectively. Enteral nutrition was given in 13% of preoperative cases and 19% of
      postoperative ones; the others received parenteral nutrition. When compared to
      the recommendations by the Consensus Conference, these results show an
      insufficient use of preoperative artificial nutrition in patients with
      malnutrition (only 22% of them received it) and an excessive use in postoperative
      patients, particularly after lower abdominal surgery. Furthermore, the caloric
      intake was in accordance with the recommendations in only 20% of the cases. It
      was too high in 38% of the cases and insufficient in 47% of them. Similarly, the
      postoperative nitrogen intake complied with the recommended figures in only 5% of
      the cases. CONCLUSION: This study highlights large discrepancies between the
      recommendations by the Consensus Conference and current practice patterns. It
      questions the efficiency of this therapy as it is implemented today and generates
      high and unwarranted expenses.

PMID- 8734236
TI  - [Pneumatic tourniquets in orthopedics].
AB  - Pneumatic tourniquets, often used to provide a bloodless operating field, carry a
      risk of adverse effects. Limb exsanguination by gravitation is less aggressive
      than by mechanical means. Skin, muscles, nerves and vessels suffer maximally
      under tourniquet because of mechanical pressure, with both a sagittal force,
      responsible for compression and an axial force responsible for stretchening. All
      parts of the limb are therefore affected by ischaemia. The restarting of
      circulation will also increase lesions at the microcirculatory level, responsible
      for the "no reflow" phenomena. Transient reperfusion intervals are not
      necessarily beneficial. These effects will significantly contribute to the post
      tourniquet sensory motor injuries. The tourniquet increases the risk of sepsis.
      Tourniquet release allows metabolites from the leg to enter into the circulation,
      and also carries a risk of pulmonary thromboembolism. Carbon dioxide is
      eliminated by spontaneous hyperventilation under regional anaesthesia. If not
      eliminated by an increase of mechanical ventilation during general anaesthesia,
      it may raise intracranial pressure in head trauma patients. Various chemotactic
      and cytolytic agents may cause lung injury. Mobilization of blood volume at
      tourniquet placement and release may have detrimental haemodynamic effects in
      patients with coronary or cardiac insufficiency. The tourniquet increases
      arterial pressure after 20 to 25 minutes under general anaesthesia. Regional
      anaesthesia is considered as the technique of choice for the prevention of
      "tourniquet hypertension", closely linked to pain and relievable by local
      anaesthetics. Tourniquet modifies also the pharmacokinetics of anaesthetic and
      other agents. It generates hyperthermia, especially in children. Prospective and
      comparative studies did not show any advantage as far as duration of surgery and
      amount of blood loss are concerned. In order to minimize its side effects, the
      tourniquet must be used within the frame of a strict procedure, with a well
      adapted and regularly checked equipment. Duration of ischaemia should be as short
      as possible and not continue for more than two hours, with a reperfusion of 15
      minutes every hour. Local hypothermia seems to be a safe means for decreasing
      side effects.

PMID- 8734235
TI  - [Do corticotherapy and hemodilution decrease postoperative inflammation after
      maxillofacial surgery?].
AB  - OBJECTIVE: To assess the efficiency of corticosteroids and preoperative acute
      normovolaemic haemodilution (PANHD) in reducing postoperative inflammation after
      maxillofacial surgery. STUDY DESIGN: Randomized clinical trial. PATIENTS: Thirty
      two patients scheduled to undergo maxillary osteotomy for facial dysmorphia were
      randomized into four groups of eight (PANHD or not; corticosteroids or not).
      METHODS: PANHD decreased haematocrit to 30%. In the corticosteroid groups,
      methylprednisolone 1.5 mg.kg-1 was given intravenously at the beginning of
      surgery (after PANHD in haemodiluted group), and after surgery, 1.5 mg.kg-1 iv
      daily for three days. Postoperative inflammation was assessed with an X-Ray
      technique (radiotelemetry) providing data on tissue thickness (extent of facial
      oedema), and by measurement of plasma concentrations of four acute phase proteins
      during the first postoperative week. RESULTS: No change in facial oedema and in
      acute phase proteins occurred with PANHD. Corticosteroids decreased postoperative
      oedema and acute phase proteins. CONCLUSION: Corticosteroids decrease
      postoperative inflammation after maxillofacial surgery but not PANHD.

PMID- 8734237
TI  - [Anaphylactic shock after tourniquet removal in orthopedic surgery].
AB  - Case report of six patients who experienced symptoms of severe anaphylactic
      shock, after tourniquet release at the end of minor orthopaedic surgery of the
      limbs under regional anaesthesia. The immunological mechanism of the shock was
      confirmed by prick tests. The causative agent was rifamycin SV used for cleaning
      the surgical wound prior to its closure. In case of repetitive surgery and/or in
      allergic patients the use of another antibiotic or the simple cleaning of the
      wound with normal saline should be considered. In case of surgery using a
      tourniquet, an iv access should be maintained for 1 hour after tourniquet release
      and the patient closely monitored in the recovery room. The allergologic
      assessment should take place 3 to 6 weeks later and include all drugs
      administered during the 10 minutes preceding the occurrence of shock.

PMID- 8734238
TI  - [Chylothorax following closed thoracic injury].
AB  - Chylothorax following blunt chest trauma is a rare event. The presence of a
      cloudy or milky persistent pleural effusion should suggest the possibility of its
      chylous origin. The diagnosis is made by analysis of the fluid obtained either
      from thoracentesis or tube thoracostomy. A lymphangiogram can show the site of
      the lesion, but computed tomography is a more recent and probably as helpful
      diagnostic test. An efficient control of the chylous effusion may be facilitated
      by using a fat-poor enteral nutrition and parenteral nutrition, which prevents
      malnutrition. Surgical ligation of the thoracic duct is relatively simple and
      efficient. It is indicated when the daily chylous flow is over 500 mL after 2 or
      3 weeks of medical treatment or in case of weight loss.

PMID- 8734239
TI  - [Prolonged apnea after suxamethonium administration during staphylococcal toxic
      shock].
AB  - A toxic shock syndrome occurred after a femoral nail removal requiring revision
      surgery. After administration of suxamethonium (1 mg.kg-1), an apnoea prolonged
      over 45 minutes was observed. The trachea was extubated 105 minutes after
      suxamethonium administration. For the nail removal, two days before, the
      anaesthetic had been given by the same anaesthesiologist, with a similar
      protocol. Apnoea extended over 20 minutes. The day of the revision surgery,
      plasma cholinesterase activity was 410 UI.L-1 and reached 910 UI.L-1, 9 months
      later. Dibucaine number was 20 and fluorure number 17. The apnoea was in relation
      with a genetic plasma cholinesterase deficiency increased by the toxic shock
      syndrome. Shock and hepatic insufficiency were suspected to contribute to the
      decrease in plasma cholinesterase. Suxamethonium should be avoided in case of
      toxic shock syndrome.

PMID- 8734240
TI  - [Carbon dioxide embolism during hysteroscopy followed by transient blindness].
AB  - A 43 year-old woman, with uterine bleeding and right ovary cyst, was scheduled
      for hysteroscopy-curettage and laparoscopy. Her history was unremarkable. After
      induction of general anaesthesia and tracheal intubation (propofol, fentanyl,
      vecuronium), anesthesia was maintained with N2O/O2 (60%/40%) and isoflurane 1 vol
      %. The patient was placed in the dorsal lithotomy position. Two minutes after the
      beginning of CO2 insufflation for hysteroscopy, a ventricular tachycardia with a
      circulatory arrest suddenly occurred. Insufflation was stopped, cardiopulmonary
      resuscitation started and lignocaine 100 mg iv administered. The haemodynamic
      status improved rapidly with a return to sinusal rhythm and stable blood pressure
      within two minutes. In the recovery room, the patient was restless and
      experienced blindness for 3 hours. Physical examination and all investigations
      (EEG, brain CT scan, carotid Doppler and transoesophageal echocardiography) were
      normal. The most probable diagnosis was a CO2 venous embolism associated with an
      arterial paradoxal embolism responsible for the temporary blindness.

PMID- 8734241
TI  - [Cardio-thyrotoxicosis with arrhythmia disclosed by an embolic cerebrovascular
      accident].
AB  - We report a case of thyroid cardiomyopathy from an iodine overload in a patient
      admitted for a cerebrovascular accident. The diagnosis was suggested by a
      hyperkinetic circulatory status and confirmed by the increased circulating
      thyroid hormone concentrations. Treatment improved the haemodynamic status,
      however the patient died from a cerebral herniation.

PMID- 8734242
TI  - [Paraplegia after cardiac arrest].
AB  - We report a case of a permanent flaccid paraplegia, with a sensory loss at T12
      level, not associated with cerebral damage, subsequent to a cardiac arrest of 15
      minutes duration, in a 67-year-old patient, undergoing haemorragic surgery for
      gangrenous purulent cholecystitis. Besides cardiovascular collapse and subsequent
      circulatory arrest, possible favouring factors include anatomical anomalies in
      the territory of anterior spinal artery, surgical posture with hyperlordosis
      generating venous stasis, emergency haemostatic maneuvers with compression of the
      arterial territory providing spinal blood supply. Spinal cord lesions are
      probably more frequent than expected, as the often associated cerebral anoxic
      encephalopathy impedes their recognition. Only a systematic anatomopathological
      examination of the spinal cord, in patients who died after a cardiac arrest,
      would provide the accurate incidence of spinal complications.

PMID- 8734243
TI  - [Hemorrhage complicating heparin treatment in a patient with myxedema].
AB  - A 75 year-old woman was admitted for a myxoedematous coma. Treatment included a
      prophylactic administration of low molecular weight heparin. During recovery from
      coma she experienced pain in her right calf. The anticoagulant therapy was
      switched to subcutaneous calcium heparin. However, the latter had to be
      discontinued due to the formation of a haematoma of a thigh. Clinical and
      biological data were in favour of a mechanism of heparin stocking during coma
      followed by its release during recovery.

PMID- 8734244
TI  - [Transfer hypokalemia induced by norepinephrine infusion].
AB  - We report a case of a severe hypokalaemia by intracellular shift of potassium in
      a sedated and ventilated head trauma patient. The kalaemia which was 3.9 mmol.L-1
      at admission in the intensive care unit decreased to 1.3 mmol.L-1 during a
      perfusion of noradrenaline (0.3 micrograms.kg-1.min-1). Following the decrease of
      the noradrenaline dose, and administration of potassium, the kalaemia rapidly
      increased to 5.3 mmol.L-1 carrying a risk of arrhythmia. Therefore, kalaemia and
      ECG should be closely monitored when the noradrenaline doses are reduced. The
      causes of transcellular shift of potassium are reviewed.

PMID- 8734245
TI  - [Difficult intubation. French Society of Anesthesia and Intensive Care. A
      collective expertise].

PMID- 8734246
TI  - [Claims related to anesthesia at the University Hospitals of Paris].
AB  - OBJECTIVE: To evaluate the number and the reason of anaesthesia-related
      malpractice claims in university hospitals of Paris. STUDY DESIGN: Retrospective
      study. METHODS: From December 1977 to December 1994, 1,185 claims, originating
      from all departments, dental trauma excluded, were reviewed and classified by one
      medical expert. They were analyzed with regard to type of activity responsible
      for the damage. RESULTS: Out of the 789 claims resulting from surgical activity,
      41 were directly anaesthesia-related. The most frequent problems were the
      neurological complications of spinal or epidural anaesthesia (n = 10), and the
      consequences of difficult intubation or aspiration of stomach contents (n = 5). A
      series of 19 damages due to posture was difficult to classify as surgery- or
      anaesthesia-related. In the 41 anaesthesia-related claims, an indemnification was
      alloted to seven (5.2%). This rate was similar to that for surgical activity
      related claims. However, the amount of the anaesthesia-related malpractice
      compensations was equivalent to 26% of those alloted to the surgery-related
      claims and to two-thirds of the indemnifications equal to or above 2,000,000 FF.
      CONCLUSIONS: There are few anaesthesia-related claims in the Paris university
      hospitals. Only few claims result in a compensation. By contrast, when a
      indemnification is alloted, its amount is very high. Locoregional anaesthesia
      seems to be at a higher risk for malpractice claims.

PMID- 8734247
TI  - [Decrease in plasmatic cholinesterase activity in severe bacterial infections:
      comparison with the decrease observed in severe liver cirrhosis].
AB  - As the influence of sepsis on plasma cholinesterase activity is not clearly
      established, plasma cholinesterase activity was measured in 30 healthy surgical
      orthopaedic patients, 11 patients with severe postoperative infections and 18
      patients with patent cirrhosis (Child-Pugh C). Plasma cholinesterase activities
      were significantly decreased (P < 0.001) in patients with postoperative
      infections (1,706 +/- 535 Ul.L-1) and in those with patent cirrhosis (1,318 +/-
      538 Ul.L-1) in comparaison to healthy surgical patients (4,716 +/- 1,232 Ul.L-1).
      The decrease in patients with postoperative infections and in those with patent
      cirrhosis was similar. It remains to be assessed whether the activity of
      anaesthetic agents biotransformed by plasma cholinesterase is modified during
      severe infections.

PMID- 8734248
TI  - [Inspiratory aid with facial masks during acute respiratory failure without
      hypercapnia].
AB  - This prospective study assessed, in 10 conscious patients without a history of
      chronic respiratory disease, the feasibility of mechanical pressure support
      ventilation with PEEP by face mask for the treatment of acute respiratory failure
      without hypercapnia. Pressure support level was determined to obtain a VT of 5 to
      10 mL.kg-1 and a decrease of respiratory rate of more than 20%. FIO2 and PEEP
      levels were determined to obtain a SpO2 > 92% and a PaO2 > 70 mmHg. The
      efficiency of the technique was assessed through the time course of respiratory
      rate, PaO2, PaCO2 and SaO2. The technique was efficient in all patients and
      tracheal intubation was not required. During face mask ventilation, a significant
      decrease in respiratory rate and an increase in PaO2 and SaO2 were observed.
      Pressure support ventilation with PEEP by face mask is an efficient technique for
      the treatment of acute non hypercapnic respiratory failure in conscious and
      cooperative patients.

PMID- 8734249
TI  - [Argyria and anesthesia].

PMID- 8734250
TI  - [Fatal pulmonary Pasteurella infection of unknown origin].

PMID- 8734251
TI  - [Cardiac arrhythmia caused by massive resorption of glycine during hysteroscopy].

PMID- 8734252
TI  - [Research of preferential indications of patient-controlled analgesia in
      orthopedics and traumatology].

PMID- 8734253
TI  - [Apropos of blood patch after thoracic epidural anesthesia].

PMID- 8734254
TI  - [Limits of sumatriptan in the treatment of headache after dura mater puncture].

PMID- 8734256
TI  - [Difficult intubation: an English solution].

PMID- 8734255
TI  - [Difficult deliveries treated with sufentanil spinal anesthesia at the end of
      labor].

PMID- 8734257
TI  - [9th meeting of the Anesthesia-Intensive Care in Otorhinolaryngology Club. Paris,
      1 December 1995].

PMID- 8734258
TI  - [Neuropeptides and nasal mucosa: a general review and update].
AB  - Following a review of the literature, the authors focused their interest on the
      sensitive physiology of the biochemistry of the nasal mucosa. After a general
      presentation of the neurotransmitter molecules studied (the tachykinins), the
      authors have determined their presence in the sensitive afferent nerves of the
      pituitary gland, evidencing their co-existence with various other neuropeptides.
      The distribution of these molecules was studied, given their capacity of acting
      on peripheral tissular receptors. The widespread distribution and the
      considerable potential of such neuropeptides reveal the important they play in
      nasal physiology.

PMID- 8734259
TI  - Mucocele of the maxillary sinus.
AB  - The maxillary sinus mucocele is a rare condition and it usually presents
      clinically as a benign tumor. Sixteen patients were evaluated. A previous history
      of surgery or injury to maxillary sinus was obtained in 12 cases, the diagnosis
      being confirmed by computed tomography imaging. Recovery is often complete after
      Caldwell-Luc operation. The authors discuss some important aspects of diagnosis
      and treatment.

PMID- 8734260
TI  - [Zygomatic-orbito-malar fractures. Apropos of 85 cases].
AB  - Our retrospective study has concerned 85 cases of zygomatic-orbito molar
      fractures, hospitalised and treated from january 1983 to december 1992. 86% of
      patients were men. The young adult is interested in 78% of cases. The traffic
      accidents are predominant in 45%. The diagnosis is especially, made by the clinic
      and confirmed by the radiology. The abstension is justificate in 27, 1% due to
      the absence of deplacement and associated disorders. The orthopedic treatment
      concerns the len deplaced (20% of cases) and stable molar fractures. The surgery
      such as reduction with osteosynthesis or reconstruction of floor is realised in
      55% of patients presenting deplaced fractures with norphologic and/or fonctionel
      disorders. The evolution is good in general. Few sequellaes has been noted in 25%
      cases. The authors insist on the interest of the precocity of diagnosis and
      treatment and on the multidisciplinar collaboration which permit an adapted
      treatment with few sequellaes.

PMID- 8734261
TI  - [Current knowledge on the action of retinoids in carcinoma of the head and neck].
AB  - The retinoids are a pharmacologic class based on the vitamin A or retinol. The
      most known related derivatives are the all-trans (ATRA), 13 and 9 Cis retinoic
      acids. The antitumor and differenciative activities have been demonstrated in: in
      vitro, in vivo and clinical studies. In head and neck cancers, the clinical phase
      III trials in chemoprevention of second primary tumors have shown discordant
      results related to the type of retinoic acid. Nuclear retinoic acid receptors are
      members of the steroid-thyroid and vitamin D3 superfamily of nuclear receptors
      which regulate differenciation proliferation and apoptosis in cooperation with
      mediated proteins of the apoptosis (especially p53 protein). A thorough knowledge
      on the earlier mechanisms involved in carcinogenesis of squamous cell carcinomas
      would lead to futur reversal therapy with the reversal of pathologic to normal
      tissues by the restauration of mechanisms of the physiologic control. This futur
      clinical trial research could provide cancer prevention and control by the
      induction of cellular differentiation rather than proliferation (retinoids)
      and/or the expression of tumor-suppressor genes (p53 protein transfection).
      Finally, the retinoids treatment should be performed in control studies because
      of the toxicity at high doses.

PMID- 8734262
TI  - [Introductory chemotherapy in epidermoid carcinoma of the head and neck. Apropos
      of a retrospective study of 293 patients].
AB  - The authors present a retrospective study of 293 patients treated by neoadjuvant
      chemotherapy for squamous cell carcinoma of the head and neck without metastases.
      The results are globally analyzed for all localizations, as well as separately
      for each localization (larynx, hypopharynx, oropharynx). The aims of this study
      are to evaluate the results of neoadjuvant chemotherapy in the different tumor
      sites of the upper aerodigestive tract, to identify the predictive factors of a
      complete response, and to ascertain if neoadjuvant chemotherapy allows to
      alleviate the locoregional treatment without compromising survival. In laryngeal
      cancers, the organ conservation rate was 20.8%. If chemotherapy does not improve
      survival in patients with laryngeal cancer, it should be noted that survival of
      patients who had a total response of their tumor to chemotherapy is better than
      that of non-responders. In hypopharyngeal cancers, the organ conservation rate
      was 30% and no statistically significant difference in survival was noted as a
      function of the different parameters studied. As for oropharyngeal cancers,
      chemotherapy obtained, in our series, a total clinical response, and thus
      avoiding oropharyngeal surgery, in 46.2% of cases. In this localization, the
      survival of totally-responding patients is greater in a statistically significant
      manner at 5 years than in non-responding patients. Globally, chemotherapy does
      not improve survival, but does allow for a gain in the quality of survival,
      permitting a non-negligible rate of organ preservation as a function of tumor
      site. The tumor stage, the lymph node status, as well as the initial performance
      index represent predictive factors of total response to neoadjuvant chemotherapy.
      Analysis of our results had led us to reserve neoadjuvant chemotherapy in T3
      laryngeal and hypopharyngeal cancers, in T3 cancers of the tonsil and the
      tonsiloglossal fold, as well as T2-T3 tumors of base of the tongue and soft
      palate.

PMID- 8734263
TI  - Detection of deglutition disorders after reconstructive laryngectomy. Clinical
      and radiological evaluations.
AB  - Subtotal reconstructive laryngectomy is an appropriate surgical procedure for
      intralaryngeal squamous cell carcinoma. After this surgery the functions of the
      larynx are greatly modified. These functions may be retained if at least one
      cricoarytenoid is preserved with good function. The aim of our study was to
      determine the recovery of swallowing in the late postoperative period and to
      establish the possible causes of dysphagia. 34 patients previously submitted to
      reconstructive laryngectomy were studied by clinical and endoscopical evaluation
      as well as videofluoroscopic examination. The results of our study confirm what
      has been reported by other authors, that is that the sphincter function greatly
      altered in the early postoperative period, is progressively restored, especially
      when both arytenoids are preserved. Videofluoroscopic examination frequently
      showed the asymptomatic false passage of liquid boluses.

PMID- 8734264
TI  - Efficacy of prophylactic elective neck dissection in the treatment of cancer of
      the larynx.
AB  - The effectiveness of elective neck dissection for treatment of cancers of the
      head and neck is controversial. We report a restrospective study of 142 patients
      treated at our hospital between 1974 and 1994 for squamous cell carcinomas of the
      supraglottic larynx. At the time of surgery, none of the patients had palpable
      cervical adenopathy. All patients underwent tumour resection, while 55
      additionally underwent functional elective neck dissection. Elective neck
      dissection had no significant effects on either the risk of subsequent
      development of ipsilateral cervical adenopathy or on survival. In view of these
      results, we do not consider elective neck dissection to be beneficial as a
      routine strategy for management of carcinomas affecting the supraglottic larynx.

PMID- 8734265
TI  - [Cholesteatoma of the middle ear in children. Apropos of 160 cases].
AB  - Cholesteatoma of the middle ear in children is a current topic and authors are
      not yet unanimous as far as surgical treatment is concerned. We report our
      experience on 160 cases of cholesteatoma observed in 150 children aged from 4 to
      15 years old. The first complications represent the reason for consulting in 36%
      and bilateral affection in 15% of the cases. We have practised the "open
      technique" in 62%, the "closed technique" in 38% of the cases. The "second look"
      operation for a residual cholesteatoma, or a recurrence constitute 26% of cases
      after the closed technique. Our choice of the open technique is explained by the
      social and economic standard of the patients, the state of the mastoid, the
      frequency of the complications mainly intracranial ones, and the types of lesions
      encountered during the operation. According to this serie, we can review the data
      of the literature, and analyse the different points of view.

PMID- 8734266
TI  - Mucormycosis of the paranasal sinuses.
AB  - Between 1989 and 1992 we had two cases of mucormycosis. The first patient
      presented with left hemiplegia: radiologic studies showed a right sphenoidal
      sinus mass, cerebral ischaemic infarction and occlusion of the right carotid
      artery. The second patient was seen with an abscess of the hard palate after long
      term steroid therapy. CT scan showed a soft-tissue mass occupying the maxillary
      sinus, which had eroded its walls and spread to palate, orbit and ethmoidal
      cells. We have emphasised the presence of hyperglycemia in both cases, the marked
      tendency of this lesion to invade blood vessels, and the good results obtained by
      combining liposomal amphotericin B with radical surgical debridement.

PMID- 8734267
TI  - Rhinocerebral mucormycosis: predisposing factors, diagnosis, therapy,
      complications and survival.
AB  - Mucormycosis is the most acutely fatal fungal infection of the human being (5).
      Although relatively uncommon, its morbidity makes it an extremely important
      disease for the Otolaryngologist-Head and Neck Surgeon. A review of 11 cases of
      rhinocerebral mucormycosis (nine female and two male patients) admitted from 1961
      to 1994 at Hospital das Clinicas, University of Sao Paulo was undertaken. The age
      range was from eight months to 49 years with a median age of 31 years. In the
      current study, we present and discuss the predisposing factors, the methods of
      diagnosis, the treatment given the complications observed and the survival of the
      disease. The survival rate for paranasal sinus mucormycosis in this study was
      72.7% (8/11). All deaths occured within the first month after diagnosis and
      institution of treatment. All the patients that died presented with diabetic
      ketoacidosis. Hemiplegia as a neurological complication of the disease was seen
      in 66.6% (2/3) of the deaths. Survival analysis (Fisher Test p < 0.05) indicates
      that diabetic ketoacidosis and hemiplegia are negative prognostic factors in
      mucormycosis survival. The authors intend to add some more information to the
      limited literature on paranasal sinus mucormycosis.

PMID- 8734268
TI  - [Apropos of a case of laryngeal granular cell tumor].
AB  - The granular cell tumor, or Abrikossofs tumor, is a benign rare neoplastic
      disease, which affects the larynx in approximately 6% of all the described
      locations. Its nervoux origin is admitted by the majority of the specialists and
      its treatment is only surgical. After describing the histopathology and the
      clinical characteristics of the lesion, we describe a most unusual atypical
      endolaryngeal location. In our review we have not found any case described as
      such.

PMID- 8734270
TI  - [Mandibular reconstruction in benign tumors of the mandible].
AB  - The authors report ten cases of reconstruction in the mandibular interrupter
      substance wast after excision of the large benign tumors which dominated by
      ameloblastoma. The reparation is realised by free no vascularized bone graft, of
      ten with the iliac crest, rarely with costochondral graft. The lateral mandibular
      interrupter substance waste concerning the temporo-mandibular joint (type III) is
      frequent. The reparation often immediate, is realised by the iliac crest graft
      fixed to mandibular stump with miniatures plaques and intermaxillar blocking. The
      fonctioning and morphology results in majority is qualified to be mean with a
      follow-up between 14 and 24 months.

PMID- 8734269
TI  - [Goldenhar syndrome: apropos of a case].
AB  - We report a case of Goldenhar syndrom in thirty eight old woman who has been
      refered to us for peribulbar choristoma. The authors discuss the different
      ophthalmological, otolaryngological and general manifestation of this syndrom and
      the therapeutic modalities of the ocular anomalies.

PMID- 8734271
TI  - [Teaching of laparoscopic surgery. The end of university diplomas].

PMID- 8734272
TI  - [Current technique of gastric plasties in esophageal surgery].

PMID- 8734273
TI  - [Prognostic factors of survival in medullary cancers of the thyroid. Apropos of
      51 cases. Clinical, biochemical and immunocytochemical study].
AB  - The aim of this study was to assess the main clinical biochemical and
      immunocytochemical factors influencing survival in 51 patients operated for
      medullary thyroid carcinoma (MTC). There were 55% of women and 37% of familial
      cases. Mean age was 43 +/- 3 years. The following survival variables were tested:
      sex, age, stage, familial disease, Serum Carcino Embryonic Antigen (CEA) and
      Calcitonin (CT) levels three months postoperatively, intensity of CEA and CT
      immunostaining, percentage of cells stained for CEA and CT. The actuarial
      survival rate, including postoperative mortality (N = 1), was studied by uni and
      multivariate analysis using a Cox model (N = 31). The 5-year survival was 69 +/-
      7%. By univariate analysis, stages I or II (p < 0.0001), age of 45 years and less
      (p < 0.0001), normalized CEA levels (p < 0.006), percentage of CT stained cells
      greater than 80% (p < 0.04) and weak CT and CEA staining (p < 0.02) were
      significant predictors of increased survival rates. Age less than 45 and stages I
      or II were significant prognostic factors of goof survival on multivariate
      analysis (p < 0.001). We conclude that clinical criteria constitute good survival
      prognostic factors in patients operated for MTC. The better prognosis of familial
      cases was probably related to their earlier detection. The prognostic value of
      immunostaining remains controversial and requires further studies.

PMID- 8734274
TI  - [Colonic irrigation for colostomies. Results of a national survey among 795
      colostomized patients].
AB  - Colonic irrigation (CI) represents the procedure of choice for patients with a
      colostomy. Recent technical advances (irrigation kit) have provided patients with
      simple, safe and effective material, allowing a new expansion of this old
      concept. A total of 795 colostomates (from association's data base) were assessed
      by questionnaires 386 (49%) of them used CI: 43.5% of patients operated before
      1980 and 50% after 1980 (p < 0.005). Two thirds of patients performed Cl every
      two days, in the morning, with one liter or less of water, for 45 to 60 minutes.
      No morbidity was reported. Some patients (18%) stopped the procedure
      deliberately, but none due to a complication. Total continence during 48 H was
      observed in 48.4% of patients. Wearing a classical stomabag after CI must be
      considered to be a precaution rather than a failure. However one half of patients
      wore a simplified material (minibag, obturator, sticking plaster). The vast
      majority of patients (86%) claimed to be entirely satisfied with CI and 96%
      wanted to continue the procedure as long as possible.

PMID- 8734275
TI  - [Medical treatment of chronic radiation induced enteritis].
AB  - The aim of the primary treatment of chronic radiation enteritis is to control
      active intestinal damage. Total parenteral nutrition and systemic glucocorticoid
      should be used when radiotherapy has been performed within the preceding year, in
      the case of extensive and severe intestinal damage, without fistula or bleeding.
      Symptomatic treatment depends on the pathophysiological analysis of diarrhea and
      compensation of malabsorption.

PMID- 8734276
TI  - [Treatment of uterine fibromas].
AB  - Uterine myomas are frequent tumors, but only some of them need to be treated:
      only when they are symptomatic. After describing the role of oestrogen and growth
      factors on the development, and the value of clinical examination and imaging
      techniques (ultrasonography, outpatient hysteroscopy without anesthesia), the
      authors study the various treatments. Medical treatments essentially consist of
      progesterone and preoperative GnRH agonists or in peri-menopause (add-back
      therapy). When if medical treatment fails, surgery consists of: myomectomy and
      hysterectomy (by abdominal, laparoscopic or vaginal routes), myolysis and
      hysteroscopic resection. Three cases are isolated: infertility, pregnancy and
      menopause associated with uterine myomata.

PMID- 8734277
TI  - [Ultrasonic laparoscopy in digestive diseases].
AB  - Laparoscopic ultrasound combines the advantage of diagnostic laparoscopy with
      intraoperative ultrasonography. This new technique allows visualisation of deep
      structures that are not palpable. The technical aspects and the application in
      abdominal surgery are described. The principal indications are detection of
      common bile duct stones during laparoscopic cholecystectomy and staging of
      abdominal cancers. The information provided by laparoscopic ultrasound influences
      therapeutic decisions.

PMID- 8734278
TI  - [Radiation injury of the small intestine. Radiobiological, radiopathological
      aspects; risk factors and prevention].
AB  - Small bowel radiolesions are a dose-limiting factor in radiotherapy of the
      abdomen ether administered alone or in combination with surgery and/or
      chemotherapy. Acute radiolesions on the small intestine are frequent and related
      to the rapid turnover of mucosal cells. The acute effects of radiation are
      rapidly regressive after completion of radiation therapy. The reported incidence
      of severe late chronic radiation injury of the small intestine varies between 0.5
      and 15%. Most of chronic injuries occur between 12 and 24 months after radiation.
      Chronic radiation enteropathy is related to the low turnover of the intestinal
      wall tissues. It is characterized by progressive cell depletion, collagen
      fibrosis and obliterative vascular injury. The main factors predisposing to late
      small bowel complications are: the total radiation dose, the dose per fraction,
      the volume of small bowel irradiated, previous surgery, and chemotherapy combined
      to radiation therapy. The knowledge of the predisposing conditions of chronic
      small bowel injuries facilitates estimation of late small bowel potential
      morbidity and allows the proposal of personalised therapeutic adjustments to
      reduce this risk.

PMID- 8734279
TI  - [Mesenteric vein infarction associated with congenital antithrombin III (ATIII)
      deficiency].
AB  - A venous mesenteric infarction in a 27-year-old patient is reported. This patient
      presented a genetic quantitative AT-III deficiency without anticoagulation
      therapy. Ultrasonography revealed portal vein thrombosis and laparoscopy showed
      mesenteric vein infarction. Laparotomy was performed mmediately and revealed
      segmental infarction of 60 cm of the jejunum which was resected; the portal vein
      was considered to be partially occluded on palpation. No strangulation or
      mechanical factors were identified. Immediately postoperatively the patient
      received therapeutic doses of heparin with AT-III concentrates to increase AT-III
      levels; no recurrent thrombotic episode was observed. A systematic second-look
      operation 24 hours postoperatively showed good bowel viability. Five days later,
      long-term anticoagulation with acenocoumarol was decided. Twelve days later,
      ultrasonography showed complete portal revascularization which was confirmed by a
      third surgical operation on D60.

PMID- 8734280
TI  - [Adrenal gland epithelial cyst. Apropos of a case].

PMID- 8734281
TI  - [Fistulization of the cystic duct in a septated peritoneum after laparoscopic
      cholecystectomy].

PMID- 8734282
TI  - [Medullary cancer of the thyroid gland in France in 1995].
AB  - 2260 patients with medullary thyroid carcinoma have been registered in France in
      1995 by the GETC group. Main characteristics of the disease are reviewed in this
      paper. Many problems remain concerning screening, localisation of metastases and
      non surgical treatment.

PMID- 8734283
TI  - [Analysis of the RET gene and medullary cancer of the thyroid. Contribution to
      the diagnosis and treatment].
AB  - MTC occurs sporadically or as part of multiple endocrine neoplasia type 2 (MEN 2)
      syndromes or as familial MTC (FMTC). 97% of the patients affected with MEN 2B
      show a germline mutation in codon 918 (exon 16) within the tyrosine kinase domain
      of the RET protooncogene. In 97% of MEN 2A patients, the germline mutation
      affects one of five cysteine codons within exons 10 and 11 in the extracellular
      domain. Only 65% of FMTC patients are found to have a germline mutation of RET.
      These mutations affect either the cysteine rich domain (as MEN 2A mutations) or
      codons 768 (exon 13) or 804 (exon 14) within the tyrosine kinase domain. In
      families affected with hereditary form of MTC, mutation analysis is now commonly
      used to determine genetic status. Individuals without the mutation would be
      considered unaffected and would not require further biochemical screening.
      Individuals who inherit the MEN 2 mutation would undergo biochemical screening
      tests and have thyroidectomy as soon as these tests are abnormal. Risk of
      phaeochromocytoma in affected patients depends on the position of RET mutation.
      This risk is high if the patient has a codon 634 mutation and low if he has a
      mutation within exon 10, 13 or 14. Frequency of adrenal follow-up could so be
      adapted with regards to the localisation of RET germline mutation. When a new MTC
      case is diagnosed, the distinction between a true sporadic and a de novo
      hereditary case is important for future clinical management of both the patient
      and his family. The absence of RET exons 10, 11, 13, and 14 germline mutations
      appears to rule out MEN 2A to a high probability. However the presence of a
      familial form of MTC cannot be excluded conclusively. Since codon 918 somatic
      mutations are found in 25% of MTC from truly sporadic cases, mutation analysis of
      RET in tumour DNA may help in distinguishing the sporadic cases from those that
      are in fact heritable.

PMID- 8734284
TI  - [Hypercalcitoninemia in conditions other than medullary cancers of the thyroid].
AB  - Serum calcitonin (CT) assays are the most useful tumoral marker for the diagnosis
      and follow up of medullary thyroid carcinoma (MTC). Since 1988 the sensitivity
      and specificity of CT assays have been considerably improved. Normal basal and
      pentagastrin (Pg) stimulated CT ranges remain to be established and it appears
      necessary to determine the pathological circumstances which may be responsible
      for hypercalcitoninemia in addition to MCT. By reviewing literature and data from
      the "Groupe d'Etude des Tumeurs a Calcitonine": a/we compared basal and Pg
      stimulated CT values obtained with two commercially available immunometric CT
      assays and we observed that CT values measured by the CT-EASIA MEDGE-NIX kit were
      three fold the values obtained by suing the hGH ELSA CIS BIOINDUSTRIE Kit; b/we
      determined that hypercalcitoninemia may be observed in isolated C Cell
      Hyperplasia (HCC) surrounding either lymphocytic thyroiditis or follicular
      thyroid carcinoma loci, in chronic renal failure on maintenance hemodialysis, and
      in various neuroendocrine tumors. Surprisingly, the hypercalcitoninemia related
      to HCC has been found in genetically unaffected members (without any identified
      gene RET mutation) of both a Multiple Endocrine Neoplasia type 2A and isolated
      familial hereditary MTC.

PMID- 8734285
TI  - [Non-neoplastic hypercalcitoninemia. Pathological anatomy].
AB  - Normal C-cells are classically concentrated between the upper and middle thirds
      of each thyroid lobe and account for less than 1% of the thyroid gland volume. C
      cell hyperplasia (CCH), defined as the presence of at least 3 low-power
      magnification (x100) microscopic fields containing more than 50 C-cells and at
      least 40 cells/cm2 was first described in a familial context of MEN2. It was then
      observed in many other conditions, especially in association with chronic
      lymphocytic thyroiditis or with thyroid tumors other than medullary thyroid
      carcinoma (MTC). In members of a MEN2 family, carrying a RET mutation, CCH is
      constant and associated with micro-MTC. At least 20% of patients with chronic
      lymphocytic thyroiditis or with a thyroid tumor other than MTC have CCH that, in
      a few cases, is associated with hypercalcitoninemia. 20 % normal subjects meet
      quantitative criteria of CCH. Patients belonging to a MEN2 family, without a RET
      mutation but presenting hypercalcitoninemia, could belong to this group. HCC
      appears to be a pre-neoplastic condition only in patients carrying a RET
      mutation. Under other circumstances, HCC may be either a reactive or even a
      normal condition.

PMID- 8734286
TI  - [Detection of residual lesions and metastases of medullary thyroid cancer].
AB  - Persistent hypercalcitoninemia represents a frequent situation particularly in
      case of inadequate surgery of medullary throid carcinoma (MTC). This event
      conducts to a surgical re-exploration after excluding the presence of distant
      metastases. After adequate initial surgical treatment the localisation of the
      residual or recurrent tumor tissue is often difficult with conventional imaging
      techniques. Immunoscintigraphy and selective venous sampling for calcitonin
      measurements have a good diagnostic sensitivity for cervical or mediastinal
      localisations and also for distant metastases. However complete remissions are
      not the rule after cervical and/or mediastinal reintervention which are proposed
      to patients who are free of distant metastases. This underlines the necessity of
      early diagnosis of MTC and adequate first neck operation.

PMID- 8734287
TI  - [Role of non surgical therapeutics in the treatment of patients with medullary
      cancer of the thyroid].
AB  - Medullary thyroid carcinoma (MTC) is a rare endocrine tumour secreting the
      calcitonin (CT), its main tumoral marker, occuring as a sporadic or a familial
      disease. These diseases are associated with a 5-years prognostic from less than
      50 to 100%, depending on the tumoral stage at the diagnosis time. The surgical
      management is demonstrated to be able to obtain a biological recovery in some
      patients. The other therapeutic means have no or poorly effects on the MTC
      evolution. Partial and transient responses are described for 15 to 20% of the
      patients with the use of multiple trials of chemotherapy. The external
      radiotherapy may have some little effects on local tumoral involvement without
      influence on the survival rates as compared to the surgery alone. The hormonal
      therapy with somatostatin analogues and the metabolic scintigraphies using MIBG,
      somatostatine analogues, radio-active iodine have no therapeutic effects
      demonstrated. The development of targeted therapy by the use of specific
      monoclonal antibodies, such as anti-CEA radiolabeled antibodies, is to be
      evaluated. The prognostic factors, as defined in large series of patients
      studied, does not necessary reflect the aggressiveness of the tumour. Thus, the
      therapeutic approach of MTC patients must take into consideration that the
      biologic activity of the disease does not implicate an aggressive disease. The
      evaluation of CT and CEA circulating levels remains of prognostic value and a
      useful tool for the practicians for the management of MTC patients.

PMID- 8734288
TI  - [Cancers of the thyroid. Value of a regional registry on 627 patients diagnosed,
      treated and followed by a multidisciplinary team].
AB  - Since 1966, data from 1536 patients with a thyroid carcinoma, living in the
      French region Champagne-Ardenne, a geographical area with 1,350,000 inhabitants
      were registered. The creation of a multidisciplinary group and the involvement of
      the general practitioners, allowed us to reach an exhaustive and continued
      registration process for the French administrative area of Marne and Ardennes
      (855,000 inhibitants, 627 patients). The sex-ratio F/M was 3.8 and the median
      ages were respectively equal to 46 [10-93] and 52 [13-82] in females and males.
      In the age groups 10-14 and 15-19, 3 cases and 13 cases were respectively
      registered. An history of external irradiation was noted in 2.9% of the patients.
      The study of the incidence around the Chooz nuclear plant (Ardennes) did not show
      an increase of the risk. For the French administrative area Marne and Ardennes,
      for the period 1975-1979, the incidence rates, standardized on the European
      population, were equal to 1.75/100,000 in males (SD = 0.15) and 6.38/100,000 (SD
      = 0.29) in females. These values among the highest from the data published by the
      other European registries should be explained by a more intensive diagnosis
      procedure and an improvement in the accuracy of histological diagnosis. An
      increase of the incidence rate was observed between the periods 1975-1983 and
      1984-1992 from 1.04 to 2.05/100,000 and 4.99 to 6.39/100,000 in males and females
      respectively. This was associated with changes in clinical and histological
      features and an improvement in survival curves. For patients under the age of 19,
      we have compared both periods before and after the accident of Chernobyl. The
      incidence rates increased from 0.13 to 0.45/100,000 and 0.49 to 1.81/100,000 in
      the age groups 10-14 and 15-19 respectively. This change was at the order of
      magnitude to this observed in our adults population. We did not found the
      histological aggressiveness which characterized the Chernobyl-induced thyroid
      cancer in children. The knowledge of the significant prognostic factors
      determined by multifactorial analyses is a major foundation of our therapeutic
      strategy.

PMID- 8734289
TI  - Activating mutations of the TSH receptor gene cause thyroid diseases.
AB  - Spontaneous mutations have been identified in the gene encoding the thyrotropin
      receptor, the effect of which is to activate the receptor in the absence of
      hormone. When they occur within thyrocytes (somatic mutations) activating
      mutations cause clonal expansion of the cells into a hyperfunctional thyroid
      adenoma (toxic nodule). Our results demonstrate that this pathophysiologic
      mechanism accounts for the majority of toxic adenomas (9 mutations found out of
      11 adenomas). The remaining cases are probably secondary to mutations in the G
      protein Gs. When similar mutations are present in the germ line, they cause a
      form of non-autoimmune hyperthyroidism transmitted as an autosomal dominant
      trait. Mutations of the tsh receptor gene have been found in five different
      families, including that corresponding to the original description of the
      syndrome by J. Leclere (Nancy). Structure/function studies of the various mutant
      receptors will contribute to our understanding of the mecanisms involved in the
      activation of G protein-coupled receptors.

PMID- 8734290
TI  - [Paracrine regulation of Leydig cells].
AB  - In addition to the endocrine control of Leydig cell functions by LH, paracrine
      control of Leydig cell functions has been suspected from the indirect stimulatory
      effect of FSH on Leydig cells. Coculture experiments of Leydig and Sertoli cells
      and the effect of Sertoli cell conditioned media on Leydig cells confirmed the
      production by Sertoli cells of acute steroideogenic factor(s) and factors
      involved in the positive or negative control of Leydig cell differenciated
      functions. Characterization and purification of these paracrine factors has been
      until recently unsuccessful. Another approach has been to investigate whether
      compounds of known biological activities in other systems, were produced within
      the testis and act on leydig cells. IGF-I is produced by Sertoli and Leydig cells
      under the control of their respective gonadotropin, LH and FSH. IGF-I enhanced
      hCG responsiveness of Leydig cells by increasing both LH receptor and
      steroidogenic enzymes. On the contrary TGF-beta which is also produced by Sertoli
      and Leydig cells is a potent inhibitor of Leydig cell functions. Its production
      by Sertoli cells is inhibited by FSH. Inhibin enhanced Leydig cell differentiated
      cell functions. Activin has, conversely to what has been published in the rat, a
      stimulatory effect on Leydig cell functions in the immature porcine Leydig cell
      model. The effects of these growth factors or related molecules mainly consist in
      positive (IGF-I, Inhibin, Activin) or negative (TGF-beta, TGF-alpha/EGF, bFGF)
      trophic effects regulating LH/hCG receptor number and mRNAs and steroidogenic
      enzyme mRNAs and activites, allowing regulation of the responsiveness of Leydig
      cells to LH. Thus both gonadotropins contribute, directly for LH and indirectly,
      through paracrine mecanisms, for FSH, to testosterone production.

PMID- 8734291
TI  - [Clinical and genetic study of a familial case of multiple endocrine neoplasia
      type 1 (MEN 1). From value of multidisciplinary collaboration].
AB  - Multiple Endocrine Neoplasia type 1 (MEN 1) is an autosomal dominant familial
      syndrome characterized by involvement of several endocrine glands, including
      parathyroid, pancreatic islet cells, anterior pituitary and diffuse
      neuroendocrine tissues (carcinoids). The gene causing this syndrome has been
      localized to chromosome 11 but was not cloned up-to-date. Pre-clinical diagnosis
      in predisposed MEN 1 families was based on the use of genetic linkage analysis
      with polymorphic DNA probes flanking the disease locus. The set-up collaborative
      multi-disciplinar medical and surgical network facilitates further clinical and
      genetic studies on MEN 1 families. Semiological course of the disease is complex
      and the main objective in clinical follow-up of patients and related is to limit
      the probability of misdiagnosis. The present report describe the clinical and
      genetic analysis in a MEN 1 family and the difficulties related to diagnose the
      disease. An interesting observation on two cases of hyperprolactinemia by two
      individuals further excluded by genetic analysis assess the potential risk of
      bias in genetic linkage studies in non-well documented families. Concerted
      analysis of genetic and bio-clinical data permitted the evaluation of each
      patient and to exclude the risk of MEN 1 in all children tested. This example
      demonstrates the need of a complete clinical information previously to genetic
      analysis and a multi-disciplinar and collaborative approach in follow-up of
      patients in each family.

PMID- 8734292
TI  - [Pancreatic somatostatinoma and MEN 1. Apropos of a case. Review of the
      literature].
AB  - The pancreatic somatostatinoma belongs to the type of rare endocrine tumors of
      the pancreas. We report the observation of a 54 year old woman. Previously she
      was suffering from diabetes mellitus. An abdominal ultrasonography revealed an
      endocrine tumor of the pancreatic tail. There was no specific symptomatology,
      with the exception for the hyperglycaemia. The diagnosis of somatostatinoma was
      certified post operatively by the immunocytochemistry of the tumor. Then, the
      patient developed a hypercalcaemia associated with an increase of parathyroid
      hormone. The surgery of the neck revealed three hyperplastic parathyroids,
      inducing this association as a multiple endocrine neoplasia type 1 (MEN 1). The
      patient did not develop pituitary tumor. Afterwards, scintigraphy with 111 Indium
      octreotide showed a residual tumor at the head of pancreas. Basal levels of
      somatostatine and calcium, pentagastrine test, computed tomography scan,
      arteriography were negative. The presence of a second somatostatinoma was
      confirmed by surgery and immunohistology. One year after the surgery, the patient
      remains clinically well. The pancreatic localization of the somatostatinoma in a
      MEN 1 is poorly documented. Its malignant nature can only be assured by the
      presence of metastases. The genetic detection of the MEN 1 becomes possible.
      Above all, the treatment is based on surgery and/or chemotherapy (Fluoro-Uracile;
      Streptozotocine). In our case, 111 In-octreotide scintigraphy was the only method
      demonstrating a residual focus, suggesting it could be an element of reference
      for the diagnosis and survey of somatostatinoma the watch of patients having a
      treatment for somatostatinoma.

PMID- 8734293
TI  - [Primary hyperparathyroidism and pregnancy].
AB  - We report a case of primary Hyperparathyroidism (HPT) occuring in a 36 year old
      woman, during pregnancy. This woman received medical therapy to the delivery,
      then underwent parathyroidectomy in post-partum. Primary HPT during pregnancy is
      associated with increased risk of fetal loss, neonatal and maternal morbidity.
      Neonatal hypocalcemia is due to transient hypoparathyroidism consequent to
      abnormal suppression of fetal parathyroid hormone secretion by maternal
      hypercalcemia. Maternal hypercalcemia may be masked by hypoalbuminemia during
      pregnancy and often leads to aspecific symptoms which will differ the diagnosis.
      The recommanded treatment is parathyroidectomy which should preferably be
      performed during the second trimester of pregnancy; the efficacity of medical
      treatment is poor and transient.

PMID- 8734294
TI  - Mechanisms involved in the generation of free radicals.
AB  - Free radicals are constantly formed in the human body, both by "accidents of
      chemistry" and for useful metabolic purposes. Their action is opposed by a
      balanced and co-ordinated system of antioxidant defences. Upsetting this balance
      causes oxidative stress, which can lead to cell injury and death.

PMID- 8734295
TI  - Role of DNA repair enzymes in the cellular resistance to oxidative stress.
AB  - Oxidative stress occurs in cells when the equilibrium between prooxidant and
      antioxidant species is broken in favor of the prooxidant state. It is due to
      reactive oxygen species (ROS) generated either by the cellular metabolism such as
      phagocytosis, mitochondrial respiration, xenobiotic detoxification, or by
      exogenous factors such as ionizing radiation or chemical compounds performing red
      ox reactions. Some ROS are extremely reactive and interact with all the
      macromolecules including lipids, nucleic acids and proteins. Cells have numerous
      defence systems to counteract the deleterious effects of ROS. Proteins and small
      molecules specifically eliminate ROS when they are formed. There are three
      species of superoxyde dismutases which transform the superoxyde anion O2- in
      hydrogen peroxyde H2O2 which in turn will be destroyed by peroxysomal catalase or
      by various peroxydases. There are numerous small molecules in the cell such as
      glutathion, alpha-tocopherol, vitamines A and C, melanine, etc. which are
      antioxydant molecules. ROS escaping destruction generate various lesions in DNA
      such as base modifications, degradation products of deoxyribose, chain breaks.
      These various lesions have been characterized and it is possible to quantitate
      them in the DNA of cells which have been irradiated or treated by free radical
      generating systems. The biological properties of the bases modified by ROS have
      been established. For example C8-hydroxyguanine (8-oxoG) is promutagenic since,
      if present in DNA during replication, it leads to incorporation of dAMP residues,
      leading to transversion mutation (GC-->TA). Purines whose imidazole ring is
      opened (Fapy residues) are stops for the DNA polymerase during DNA replication
      and are therefore potentially lethal lesions for the cell. Oxidized pyrimidines
      have comparable coding properties. Efficient DNA repair mechanisms remove these
      oxidized bases. In Escherichia coli cells, endonuclease III (NTH protein) and
      endonuclease VIII (NEI protein) excise many oxidized pyrimidines, whereas the FPG
      protein (formamidopyrimidine-DNA-glycosylase) eliminates 8-oxoG and Fapy lesions.
      Besides its DNA glycosylase activity, the protein FPG has a beta-lyase activity
      incising DNA at abasic site by a beta-delta elimination mechanism, and a dRPase
      activity. The FPG protein has a zinc finger motive which is mandatory for the
      recognition of its substrate. Mammalian cells have similar DNA repair proteins
      and it should be emphazized that there is conservation of the different functions
      and in most cases a remarquable homology of the amino acids sequences from E.
      coli to man.

PMID- 8734296
TI  - Estimation of peroxidative damage. A critical review.
AB  - Numerous methods have been developed to measure lipid peroxidation products and
      lipid peroxidation damage in tissues, cells and body fluids. The choice of which
      method is most appropriate depends, amongst others, on the specific interest of
      the investigator. In the routine clinical and laboratory praxis, the
      determination of thiobarbituric acid reactive substances (TBARS) under strictly
      standardized conditions is in most cases the first choice. The specificity of the
      colorimetric or fluorimetric assay can be significantly improved if combined with
      HPLC. If levels of TBARS are increased, other more sophisticated assays should be
      performed for verification. Assays are available for: Phospholipid- and
      cholesterylester hydroperoxides, aldehydic lipid peroxidation products including
      4-hydroxynonenal, fluorescent protein adducts (e.g. lipofuscin), conjugated
      dienes and antioxidants. The measurement of pentane and ethane in the exhaled air
      by gas chromatography is the only available non-invasive method. Several
      laboratories currently develop immunological assays (ELISA, RIA) for determining
      proteins modified by lipid peroxidation products (e.g. malonaldehyde, 4
      hydroxynonenal) or autoantibodies against oxidatively modified proteins. It can
      be expected that such assays will soon gain diagnostic importance.

PMID- 8734297
TI  - Reactive oxygen intermediates as second messengers of a general pathogen
      response.
AB  - Oxygen and derived ROIs became a threat for all organisms more than two billion
      years ago. Both prokaryotic and higher eukaryotic cells are able to alter their
      genetic programme in response to changes in the intracellular levels of reactive
      oxygen intermediates (ROIs). In bacteria and yeast, this response leads to the
      new synthesis of proteins that protect the induced cells from the consequences of
      oxidative damage, such as DNA strand breaks, lipid peroxidation and oxidative
      damage of proteins, thereby ensuring growth in a prooxidant environment. In
      higher eukaryotic cells, oxidative stress can be the consequence of reoxygenation
      of ischemic tissus or of exposure to environmental hazards. Intriguingly,
      multicellular organisms have also evolved cellular mechanisms to actively produce
      ROIs. In one case, the reactive compounds are needed as weapons against invading
      microorganisms. Granulocytes, neutrophils and macrophages have specialized in
      releasing of large amounts of H2O2 and superoxide. However, many other cell types
      can also inducibly produce ROIs but in amounts insufficient to threat
      microorganisms. There is increasing evidence that the small increases in ROI
      levels fulfil a role as second messengers. We propose that these pandemic
      pathogens have been conserved throughout evolution as universal pathogen
      messengers turning on genes with important functions in the immune response and
      cell proliferation. The higher eukaryotic transcription factor NF-kappa B will be
      described as a protein which is activated by ROIs under a great variety of
      pathogenic conditions and initiates the new expression of genes with important
      roles in inflammatory, immune and acute phase responses.

PMID- 8734298
TI  - [Modulation of the oxidative burst of human neutrophils by pro- and anti
      inflammatory cytokines].
AB  - Human polymorphonuclear neutrophils (PMN) and cytokines play a critical role in
      host defences against invading microorganisms. In response to a variety of
      stimuli, PMN are a major source of reactive oxygen species (ROS) which are
      essential for bacterial killing and may induce oxidative stress in tissue
      environment. A precise regulation of the oxidase activity is therefore necessary.
      Cytokines such as TNF alpha, GM-CSF, IL-8, IL-6, IL-1 alpha and IL-1 beta
      produced during the immune and inflammatory responses to pathogens have been
      reported to interact with PMN activities. However, contradictory results have
      been reported on their direct and priming effects on the PMN release of ROS
      (oxidative burst). We have used a flow cytometry method to study the effects of
      these cytokines on the oxidative burst of PMN in whole blood, in order to avoid
      PMN activation related to isolation procedures. None of the cytokines tested
      directly activated the PMN oxidative burst, but they did have differential
      priming effects on the oxidative burst in response to N-formyl peptides. TNF, GM
      CSF and IL-8 strongly primed a subpopulation of PMN to produce H2O2 in response
      to fMLP, while IL-1 alpha, IL-1 beta and IL-6 failed to do so. Furthermore, the
      addition of TNF, GM-CSF or IL-8 to whole blood increased the capacity of a
      subpopulation of PMN to bind N-formyl peptides, a phenomenon that could account
      for the strong H2O2 production in response to fMLP following priming by the
      cytokines. These results show that, among the various cytokines tested, TNF, GM
      CSF and IL-8 strongly prime the PMN oxidative burst in response to bacterial
      peptides in whole blood and suggest that these cytokines may play a critical role
      in bacterial killing in vivo and also in the surrounding tissue injury secondary
      to pathological inflammatory reactions. In particular, TNF and IL-8 plasma levels
      as well as LPS-induced monocytic production of these cytokines ex vivo have been
      correlated with the production of ROS by stimulated PMN and with the lung injury
      score in patients with Adult Respiratory Distress Syndrom (ARDS). However,
      desensitization phenomena have also been described. In particular, in HIV
      infected patients we demonstrated a decrease of H2O2 production by PMN in whole
      blood after ex vivo priming by IL-8 and TNF followed by fMLP stimulation. This
      decrease increased with the progression of the disease and was inversely
      correlated with IL-8 plasma level. Different mechanisms could explain such
      desensitization phenomena at the receptor and post receptor level. In addition
      cytokines are involved in a complex network of regulation and anti inflammatory
      cytokines, such as IL-10, could act as a negative signal on the proinflammatory
      cytokines induced-priming of oxidative burst.

PMID- 8734299
TI  - Update on dietary antioxidants and cancer.
AB  - Advances in diagnosis and treatment of cancer, as well as increased understanding
      of the mechanisms of the disease, have provided and will certainly continue to
      provide enormous benefit to affected individuals. At the same time, interventions
      that may prevent common cancers from developing in healthy people could, at least
      in theory, afford even greater benefits to society as a whole. The hypothesis
      that antioxidant vitamins might reduce cancer risk is based on a large body of
      both basic and human epidemiologic research. A large number of case-control and
      cohort studies provide remarkably consistent data suggesting that consumption of
      foods rich in antioxidant vitamins reduce risks of developing epithelial cancers.
      These data raise the question of a possible role of antioxidants, such as
      vitamins C and E, and beta carotene, in the primary prevention of cancer as well
      ar cardiovascular disease but do not provide a definitive answer. Despite the
      lack of clear benefit, there has been a rapid increase in the consumption of
      supplements of these micronutrients. Limited randomized trial data on the role of
      supplemental antioxidants are available. A number of randomized trials are
      currently underway designed to test the hypothesis that antioxidants prevent
      chronic diseases and to evaluate the long term safety of the widespread practice
      of supplementation. Well designed and well conducted large-scale randomized
      trials are necessary to provide a definitive positive or negative result on which
      public policy can be based, or a null result that is truly informative and that
      can then safely permit the rechanneling of already limited resources to other
      areas of research.

PMID- 8734300
TI  - [Role of oxidation of lipoproteins in the pathogenesis of atherosclerosis].
AB  - There is increasing evidence suggesting an important role of LDL oxidation in the
      pathogenesis of atherosclerosis. It has been shown that oxidized LDL is present
      in vivo and that it is atherogenic in many ways. LDL sensitivity to oxidation
      depends on many factors. Oxidation occurs mainly in the arterial wall and the
      methods usually available to measure oxidation are not sensitive enough to detect
      the minimally oxidized LDL which could be present in the circulation. A more
      sensitive method would be very useful in clinical trials to test the potential
      benefits of antioxidant therapy in the prevention and/or the treatment of
      atherosclerosis. One has to wait for the results of long, prospective,
      randomized, double blind studies before considering dietary and/or therapeutic
      recommandations for the use of antioxidants.

PMID- 8734301
TI  - Pathogenic mechanisms in familial amyotrophic lateral sclerosis due to mutation
      of Cu, Zn superoxide dismutase.
AB  - Oxidative mechanisms of damage have been implicated indirectly in the damage to
      brain tissue caused acutely by ischemia or chronically by neurodegenerative
      diseases. A direct link between pathogenesis and antioxidant enzyme systems has
      come from studies of a genetic form of amyotrophic lateral sclerosis (ALS). ALS
      causes the degeneration of motor neurons in cortex, brainstem and spinal cord
      with consequent progressive paralysis and death. The disease occurs in both
      sporadic and familial forms. Some 20% of kindreds in which ALS is inherited in an
      autosomal dominant fashion have mutations in the gene (SOD1) encoding Cu, Zn
      superoxide dismutase (SOD). Several SOD1 mutations have been shown by ourselves
      and others to cause motor neuron disease when expressed at high levels in
      transgenic mice, whereas transgenic mice expressing comparable amounts of wild
      type human SOD do not show clinical disease. Thus, we have argued that motor
      neuron disease is caused by gain-of-function mutations in the human SOD1 gene.
      Our current experiments investigate the link between mutation of SOD1 and
      oxidative pathways of damage.

PMID- 8734302
TI  - Oxidative stress in Parkinson's disease and other neurodegenerative disorders.
AB  - The cause of cell death in neurodegenerative diseases remains unknown but the
      formation of free radicals and the occurrence of oxidative stress may be a common
      component of many, if not all, such disorders. For example, in substantia nigra
      in Parkinson's diseases key alterations occur, in iron handling, mitochondrial
      function and antioxidant defences, particularly reduced glutathione. These
      indices of oxidative stress are accompanied by evidence of free radical mediated
      damage in the form of increased lipid peroxidation and oxidation of DNA bases.
      The alterations in oxidative stress occurring in Parkinson's disease appear not
      be related to the administration of L-DOPA. Some alterations of oxidative stress
      are found in other basal ganglia in degenerative disorders (multiple system
      atrophy, progressive supranuclear palsy, Huntington's disease) but these have not
      been investigated to the same extent. Similarly, examination of biochemical
      changes occurring in Alzheimer's disease, motor neurone disease and diabetic
      neuropathy also suggest the involvement of free radical mediated mechanisms as a
      component of neurodegeneration. It is probable that irrespective of the primary
      cause of individual neurodegenerative disorder, the onset of oxidative stress is
      a common mechanism by which neuronal death occurs and which contributes to
      disease progression. Clearly, therapeutic strategies aimed at limiting free
      radical production and oxidative stress and/or damage may slow the advance of
      neurodegenerative disease.

PMID- 8734303
TI  - [Role of oxidative stress in aging].
AB  - In this article is presented a synthesis of the complex relationships between
      oxidative stress ageing. Free radicals are produced in a continous way but they
      are also quickly removed by very efficient defence systems. The studies trying to
      increase the antioxidants uptake in the diet or to produce transgenic animals
      overexpressing antioxidant enzymes did not lead to increased life span in
      mammals. Only transgenic drosophils for SOD and catalase lived longer than the
      parents wild type. At the cellular level, oxidative stresses speed up the passage
      of fibroblasts from young to old morphotypes. This shift increases with stress
      intensity but is also influenced by the quantity of energy available to the cell.
      Thermodynamics of open systems very well account for the experimental
      observations of cell response to stresses, oxidative stress being only one of the
      challenges faced by living cells. Oxidative stresses must be considered in
      relationship with the level of defence and turnover systems as affecting
      continuously various cellular functions with sometimes excessive production in
      pathological situations. In this case, a global response of the cell is observed
      which is the result of complex mechanisms linked to cell activation and changes
      in gene transcription.

PMID- 8734304
TI  - [Metabolism and antioxidant function of glutathione].
AB  - Glutathione (gamma-glutamyl-cysteinyl-glycine or GSH) is a cysteine-containing
      tripeptide with reducing and nucleophilic properties which play an important role
      in cellular protection from oxidative damage of lipids, proteins and nucleic
      acids. GSH regulates the metabolism of proteins and their activities by means of
      thiol-disulfide exchange. During oxidative stress, GSH plays a key role of
      protection and detoxification as a cofactor of glutathione peroxidases and
      glutathione-S-transferases. There are synergistic interactions between GSH and
      other components of the antioxidant defense system such as vitamin C, vitamin E
      and superoxide dismutases.

PMID- 8734305
TI  - [Effect of lipid intake in meals on the duodenojejunal and sigmoid motor
      responses in healthy volunteers].
AB  - OBJECTIVES: In man, fat induces a fed motor pattern in the small bowel and
      stimulates colonic motility. With a pure lipid meal, these motor effects are dose
      related. However, animal studies have suggested that the motor effects of fat are
      reduced when lipids are mixed with proteins and carbohydrates. Our aim was to
      study in healthy volunteers the duodeno-jejunal and sigmoid motor responses after
      two 750-kcal meals, one containing 28%, the other 58% lipids. METHODS: Combined
      duodeno-jejunal and sigmoid manometric sessions were performed in each volunteer
      during 3 hours after each test meal. Meal was always given 30 minutes after the
      occurrence of a phase III in the duodenum. The order of the two studies was
      randomly assigned with a minimal interval of 8 days between the two studies. The
      number of waves and the area under curve were calculated both on the overall and
      on each of the 6 successive half hours of the recording period. RESULTS: Phases
      III were interrupted at least for 3 hours by both types of meals in each
      volunteer. The overall duodeno-jejunal motor response was not different after the
      two meals and, in all cases, a progressive decrease of the motor parameters with
      time was demonstrated. A lower response in the duodeno-jejunum during the first
      postprandial hour and a delayed onset of the maximal motor activity were observed
      with the high fat meal. In the sigmoid, a motor response to food was observed in
      all volunteers without any quantitative difference between the low and high fat
      meals. CONCLUSION: A two-fold increase of the lipid fraction of a meal does not
      enhance the duodeno-jejunal and sigmoid motor responses to food. At variance, it
      reduces the first hour motor response and delays the peak of maximal activity in
      the duodeno-jejunum. Our data confirm that the specific motor effects of fat are
      modified by their combination with proteins and carbohydrates.

PMID- 8734306
TI  - [Antisecretory effects of YY peptide and neuropeptide Y at three levels of the
      small intestine in rats].
AB  - OBJECTIVES AND METHODS: The purpose of this study was to compare the effects of
      peptide YY (PYY) and neuropeptide Y (NPY) on VIP- and PGE2-stimulated intestinal
      net water flux at three different levels of the small intestine (duodenum,
      jejunum, ileum), by a technique of in situ closed loops in anaesthetised rats.
      RESULTS: VIP-stimulated net water flux was efficiently inhibited by both peptides
      at all three intestinal levels studied; PYY (ID50 about 30 pmol/kg.h) was 3 to 18
      fold more potent than NPY. PGE2-stimulated net water flux was also efficiently
      inhibited in the jejunum and ileum; PYY (ID50 about 10 pmol/kg.h) was 30 to 90
      fold more potent than NPY. A 30% inhibition of PGE2-stimulated net water flux
      could only be achieved in the duodenum with the largest dose of either peptide
      used in this study. CONCLUSIONS: PYY and NPY display potent inhibitory effects of
      stimulated net water flux at the three studied levels of the small intestine,
      except in the PGE2-stimulated duodenum. The PYY ID50s measured suggest that PYY
      may have a physiological action in regulating small intestinal water flux in the
      rat.

PMID- 8734307
TI  - [Stomach ulcers and Helicobacter pylori. Clinical, endoscopic and histological
      characteristics].
AB  - OBJECTIVES: The aim of the study was to determine in a large group of patients
      with a gastric ulcer the differences between patients, ulcers and gastric mucosa
      as related to the presence or absence of Helicobacter pylori (H. pylori).
      METHODS: This prospective study evaluated 150 patients with a benign gastric
      ulcer. A patient was considered as H. pylori positive on the basis of a positive
      culture or the presence of gastritis and another positive diagnostic test for H.
      pylori (urease test, cytology, histology, serology). RESULTS: One hundred and
      five patients were positive for H. pylori (70%) whereas 45 patients were not
      infected (30%). There were significant differences regarding the clinical
      characteristics of patients, the ulcer and the mucosa. H. pylori positive
      patients differed in terms of past history of ulcer (63 vs 12%), age (57 vs 50
      years), sex (48% males vs 24%) and consumption of non steroidal antiinflammatory
      drugs (39 vs 75%). H. pylori positive ulcers were more often single (79 vs 53%)
      and located on the small curvature (76 vs 33%). Chronic gastritis was always
      present in positive patients, with associated intestinal metaplasia (35 vs 2%)
      and atrophy (45 vs 9%). Negative patients often had a normal gastric mucosa (53%)
      or reactive gastritis (27%). CONCLUSION: Seventy percent of gastric ulcer are
      associated with H. pylori infection, corresponding to the classical ulcer. The
      majority of H. pylori negative ulcers appears to be associated to non steroidal
      antiinflammatory drugs.

PMID- 8734308
TI  - [Immunotherapy of colorectal cancers].

PMID- 8734309
TI  - [Economic assessment in health care: contribution and limits].

PMID- 8734310
TI  - [Seroprevalence of viral hepatitis A in at the Amiens University Hospital].
AB  - OBJECTIVES AND METHODS: The epidemiology of viral hepatitis A has been evolved in
      the past few years, resulting in an increasing number of people without immunity
      to this virus. Health care workers are usually considered to be a group at risk
      of contamination by hepatitis A. A sero-epidemiologic study was performed in 525
      members of the Pediatry, Gastroenterology, Internal medicine, Digestive
      radiology, kitchen and maintenance department staffs in the Amiens University
      Hospital. The aim of this study was to describe the epidemiology of hepatitis A
      and to estimate the level of occupational hazard it represents in the hospital.
      RESULTS: Age, low education level, country of origin in an endemic region and
      more than 2 siblings or children were significantly associated with the presence
      of anti-HAV antibodies. The prevalence of 50% was similar to that observed in
      other hospitals, but lower than that found in the general population.
      Seroprevalence was not higher in departments exposed to stools (Pediatry,
      Digestive endoscopy and laboratories) than in others. A higher rate of
      seroprevalence was observed in kitchen and maintenance staffs than in medical,
      laboratory and Radiology staffs, in Internal medicine than in the
      Gastroenterology Department, and in the laboratory than in Radiology Department.
      These differences disappeared after adjustment for extraprofessional parameters
      which appeared to be most important for hepatitis A epidemiology. CONCLUSIONS:
      The hospital occupational hazard for hepatitis A virus did not seem higher than
      that observed in the general population.

PMID- 8734311
TI  - [Viral hepatitis A with prolonged course in adults].
AB  - OBJECTIVE: The aim of this study was to determine the clinical and virological
      characteristics of patients with type A viral hepatitis and a protracted course.
      METHODS: Twenty-seven patients with hepatitis A virus and elevated serum ALT
      levels for more than 6 months were studied. Patients were tested for hepatitis C
      and E virus using conserved serums. RESULTS: A biological relapse was defined by
      a decrease of the serum ALT levels > or = 50% followed by a > or = 50% increase
      in the minimal value. Biological relapses occurred in all patients. The median
      time between the onset of the disease and the first relapse was 87 days. During
      relapse, jaundice and ascites were present in five and one patients,
      respectively. All patients recovered. Serum aminotransferase activities returned
      to the normal range in a median of 230 days. None of the 17 tested patients had
      hepatitis C virus antibodies. Sixteen patients were tested for hepatitis E virus
      antibodies; 8 were positive for IgG and one for IgM. Sixteen control patients
      with acute hepatitis A of short duration, matched for date and country of
      contamination, were also tested for antibodies to hepatitis E virus; 11 were
      positive for IgG and none for IgM. CONCLUSION: A protracted course of type A
      viral hepatitis is characterised by relapses with or without symptoms. The high
      frequency of a positive test for hepatitis E IgG associated with a negative test
      for IgM in patients with and without a protracted course does not suggest that
      hepatitis E virus plays a role in patients with a protracted course. These
      positive results might be due to either false positive results or to past
      contamination.

PMID- 8734312
TI  - [Compared efficiency of three strategies of management of chronic hepatitis C.
      Effect on the risk of cirrhosis 8 years after diagnosis].
AB  - OBJECTIVES AND METHODS: The goal of treating chronic hepatitis C with alfa
      interferon is to eradicate HCV infection. The actual influence of this treatment
      on the development of cirrhosis is unknown. Moreover, the poor results and the
      high cost of this treatment have caused a public health problem. Three strategies
      were evaluated by decision analysis: no treatment (S1), treatment of chronic
      active hepatitis only (S2), treatment of all chronic hepatitis (S3). For each
      strategy, we estimated the probability of the occurrence of the following events
      based on data in the literature: presence of chronic active hepatitis, chronic
      persistent hepatitis or cirrhosis at the time of diagnosis; discontinuation of
      interferon because of adverse events; biological response to treatment; incidence
      of cirrhosis 8 years after diagnosis without treatment or in case of response to
      treatment. RESULTS: The risk of cirrhosis was 28.5% with S1, 25.4% with S2, and
      25.2% with S3, 8 years after diagnosis. If HCV infection was detected early
      before cirrhosis, the number of cases of cirrhosis occurring in an 8 year
      followup period would be 45,600 with S1, 40,640 with S2, and 40,320 with S3 and
      the cost of S2 and S3 would be 1.23 10(9) French Francs (FF), and 2.57 10(9) FF,
      respectively. The mean cost to prevent one case of cirrhosis would vary from
      248,000 FF with S2 to 487,000 FF with S3. CONCLUSION: This decision analysis
      study suggests that the S3 strategy is not suitable for a population of HCV
      infected patients, because of its low efficiency and high cost.

PMID- 8734313
TI  - [Antibiotic prophylaxis and endoscopic retrograde cholangiopancreatography].

PMID- 8734314
TI  - [Peritoneal mesothelioma revealed by episodes of recurrent spontaneous
      peritonitis].
AB  - A case of a malignant peritoneal mesothelioma revealed by recurrent episodes of
      peritonitis is reported. This presentation had never been described. A 54 year
      old man presented successive episodes of appendicitis, cholecystitis and
      sigmoiditis associated with purulent aseptic peritonitis. There were no signs of
      immunodepression or vasculitis. Initial analysis of peritoneal biopsies showed
      non specific inflammation. Because of long-term asbestos exposure, these biopsies
      were reviewed. A diagnosis of peritoneal mesothelioma was made on subserous
      infiltration by mesothelioma cells, and confirmed by immunohistochemistry. The
      patient died ten months after the diagnosis of mesothelioma despite chemotherapy
      (cisplatine+interferon).

PMID- 8734315
TI  - [Portal vein thrombosis and rupture of the esophagus secondary to a barotrauma].
AB  - Portal vein thrombosis complicating a trauma is rare. We report a case of portal
      vein thrombosis associated with esophageal rupture after a blast injury due to
      the explosion of a pressurized nitrogen bottle. Portal vein thrombosis was
      discovered during oesophageal reconstruction, 70 days after the initial injury. A
      favorable outcome was observed.

PMID- 8734316
TI  - [Chronic hepatic encephalopathy treated by long-term intravenous administration
      of flumazenil in ambulatory care].
AB  - Treatment of chronic hepatic encephalopathy is difficult. Oral flumazenil has
      been proposed for long-term treatment but is not presently available on the
      market. We report the successful treatment of one case of chronic hepatic
      encephalopathy in cirrhosis without precipitating factors by low dose intravenous
      injections of flumazenil (Anexate, 1 mg/4 hours). Flumazenil is expensive and not
      always effective. We suggest reserving this treatment to highly selected patients
      (without precipitating factor, or after failure of first choice treatment).

PMID- 8734317
TI  - [Digestive endoscopy and risk of transmission of hepatitis C virus: hygiene and
      discussion].

PMID- 8734318
TI  - [Bouveret syndrome revealed by hematemesis].

PMID- 8734319
TI  - [Probable acute hemorrhagic colitis caused by isotretinoin with a test of
      repeated administration].

PMID- 8734320
TI  - [Hepatic metastases revealing neuroendocrine carcinoma of the esophagus].

PMID- 8734321
TI  - [Severe parietal cellulitis following laparoscopy for peritonitis caused by
      perforated duodenal ulcer].

PMID- 8734322
TI  - [Atypical mucinous ductal ectasia or fissured mucinous cystadenoma?].

PMID- 8734323
TI  - [Hemocholecystitis after intrahepatic portacaval anastomosis by transjugular
      approach: treatment by cholecystostomy and endoscopic sphincterotomy].

PMID- 8734324
TI  - [Fulminant hepatitis caused by flutamide].

PMID- 8734325
TI  - [Acute pseudo-angiocholitic hepatitis caused by oxatomide].

PMID- 8734326
TI  - [An odd hunting accident: acute obstruction of a biliary prosthesis caused by a
      buck shot].

PMID- 8734327
TI  - [Clear cell cancer of the gallbladder and extrahepatic bile ducts].

PMID- 8734328
TI  - [Cellular constituents and extracellular proteins involved in the pathogenic
      capacity of Streptococcus group A].
AB  - Group A streptococci (S. pyogenes) possess a number of capsule and cell wall
      associated components and release many extracellular proteins (toxins and
      hydrolytic enzymes) that are known or thought to contribute to the virulence and
      pathogenicity of the microorganism. Groupe A streptococci cause a wide array of
      infections, the most frequent of which are acute pharyngitis and pyoderma with
      two severe sequelae (acute rheumatic fever and glomerulonephritis). Other
      manifestations are scarlet fever and various soft tissue infections as well as
      sepsis and the recently characterized streptococcal toxic shock syndrome. The
      somatic components of group A streptococci include cell wall M protein, capsular
      hyaluronic acid, lipoteichoic acid, peptidoglycan, fibronectin binding protein,
      C5a peptidase and receptors for various human plasma proteins particularly IgA
      and IgG. The extracellular products are numerous and consist of among others the
      hemolytic toxins streptolysins S and O, hyaluronidase, streptokinase and
      cysteinyl proteinase as well as the superantigens erythrogenic toxins A and C
      also known as pyrogenic exotoxins.

PMID- 8734329
TI  - ["Autoantibodies" and cell aging. Does malonic dialdehyde constitute an
      immunological marker of cell aging?].
AB  - Malondialdehyde (MDA), a lipid peroxidation product, reacts with free amino
      groups of proteins to give amino-3-iminopropene (AIP) bridges which are
      immunogenic. Antibodies reacting specifically with MDA-crosslinked proteins
      preexist in the sera of healthy human subjects, and we hypothesize that they are
      implicated in processes of senescent cells recognition and elimination. Results
      obtained by immunofluorescence and flow cytometry show an immunological response
      against structures arising on cell membranes from MDA reaction with free amino
      groups of proteins. Such structures might also be implicated in autoimmunity.

PMID- 8734330
TI  - [Suppression of platelet activating factor effects (PAF) on the retina by G
      proteins inhibitors].
AB  - The Platelet Activating Factor (PAF) have been shown to alter the transretinal
      potential recorded from light stimulated isolated retina. In the present study,
      we investigated the effect of cholera and pertussis toxins on PAF-induced
      electroretinogram (ERG) impairment. Administrated alone, 2.10(-7) M PAF induced a
      very marked and rapid drop in the b-wave amplitude of the ERG. When 75
      micrograms/l of cholera toxin was coadministrated with PAF (2.10(-7) M) into the
      perfusion solution, the fall of the b-wave was not observed, suggesting that PAF
      effect on retinal function was mediated through GTP-binding protein (G-protein).
      Similarly, low-dose of pertussis toxin (5 micrograms/l) 1) were sufficient to
      antagonize PAF (2.10(-7) M) consequence on the ERG. Our results suggest that the
      irreversible and deleterious effect of PAF on ERG is mediated by a G-protein
      mechanism, located in the neural retina.

PMID- 8734331
TI  - [Aspergillus fumigatus: from saprophytism to virulence. Phenotypic and genotypic
      biodiversity].
AB  - During the last two decades, deep changes have arised in aspergillosis. Thus,
      this fungal infection mainly due Aspergillus fumigatus is becoming a serious
      public health-hazard in the growing population of immunocompromised patients.
      From literature and their own experience, the authors present a synthesis of
      phenomenons promoting this evolution: the host predisposing factors, environment
      and potential contamination sources, then the fungus itself. Genetic research
      developed into the disease-causing organism could be of major interest in
      epidemiology of aspergillosis and to identify new targets of prophylaxis.

PMID- 8734332
TI  - [Current therapeutic methods in onco-hematology].
AB  - These next years, many anticancer drugs will be available with new mechanism of
      action. The taxoid compounds: Taxol and Taxotere have been judged efficous in the
      treatment of advanced ovary and breast cancers. Also, DNA-Topoisomerase I
      inhibitors, a new enzyme molecular target, will expand solid tumors therapeutic
      strategies. The adenosine analogs represent the xnewest advances in hematology:
      fludarabine becomes the second line treatment for chronic lymphoid leukemia,
      cladribine the reference treatment for hairy cell leukemia. At least, all-trans
      retinoic acid has changed acute promyelocytic leukemia pronostic by
      differentiating tumor cells, and open a very new way of cancer treatment. All
      these agents are the first compounds available, others are still in development.
      They, all, are benefit of a productive research.

PMID- 8734333
TI  - [Effects of temperature and PH on dissolution kinetics of methotrexate in aqueous
      media].
AB  - In vitro dissolution kinetics of Methotrexate have been analysed at different
      temperatures in water at pH 1.5. After giving rise to the dissolution reaction,
      it has been possible to follow up the kinetic of dissolution and calculate energy
      activation. The pH variation allows us also to appreciate the constant behaviour
      of dissolution at temperature 310 K (37 degrees). Weilbull equation is valid with
      success for dissolution reaction as well during temperature variation and
      different values of pH. In both cases the Weibull constant b has been calculated
      and compared to constant dissolution K.

PMID- 8734334
TI  - [Stability control of a copper histidinate solution].
AB  - Some authors have suggested the administration subcutaneous of copper histidinate
      for the treatment of the Menkes disease. The purpose of this study was to control
      the complex formation of Cu (II)-L-Histidine in molar ratio 1/2 and to verify the
      stability in some conditions of determination and validation production.

PMID- 8734335
TI  - [Glorification of forgotten famous chemists: the medals of the Stanislas Limousin
      Committee].
AB  - A Committee created in 1938 by Pr Goris decided to honour Stanislas Limousin--a
      dispensing chemist who invented, among other things, medicinal Cachets and
      pharmaceutical vials--by placing a medallion bearing his effigy upon the house
      where he was born in Ardentes. Ten years later, this Committee considered that
      quite a few other dispensing chemists deserved the same honour and selected four
      of them: Eugene Choay, Charles Tanret, Emile Boudier and Claude Nativelle: the
      aim of the author was find out whether those medallions had really been affixed
      on the respective birth places of these pharmacists and if they were still in
      place. It is the case for the first two of them. Concerning Boudier, his
      medallion was affixed on his pharmacy in Montmorency and is still there. As for
      Nativelle, his medallion, if ever affixed, was laid down and recently found again
      an attic of the faculty of pharmacy.

PMID- 8734336
TI  - Epidemiology of inflammatory bowel disease: an update.
AB  - What have epidemiologic studies on IBD taught so far? Consistent findings are as
      follows: A high incidence of both CD and UC in industrialized countries and an
      increase in these areas of the incidence of CD during the years 1960-80 followed
      by a plateau phase, and a more stable pattern in UC during the same period have
      been found. A greater number of mild cases have probably been diagnosed recently.
      This also helps to explain the differences in severity and survival between
      community and referral centre groups. The male to female ratio is greater than 1
      in UC, and this is the opposite in CD. Mortality of IBD has decreased during the
      past decades. As young people are especially prone to develop IBD, most of those
      affected will have their disease for many years. In developing IBD, genetic
      influences are of importance. However, epidemiologic studies strongly point to
      possible interactions between genetically determined features and environmental
      or other factors. Of these exogenic factors smoking is the most consistent, being
      of negative influence in CD and protective in UC. Diet and oral contraceptives
      may influence disease expression, and perinatal events such as viral infections
      may alter adult susceptibility. The question remains open whether UC and CD are
      one diseases entity. Similarities in the epidemiologic features of UC and CD
      support the idea of IBD being one disease. Other findings suggest dividing UC and
      CD into further subgroups: in CD it has been suggested that fibrostenotic,
      penetrating, and inflammatory behaviour should be considered different disease
      entities; in UC some groups consider ulcerative proctitis a disease entity on its
      own, separating it from the proximally extending colitis. In therapeutic trials
      this approach has proved to be of importance, and it is not inconceivable that in
      subgroups, with regard to aetiopathogenetic mechanisms, different factors have to
      be looked for.

PMID- 8734337
TI  - The effect of Helicobacter pylori on gastric acid secretion by isolated parietal
      cells from a guinea pig. Association with production of vacuolating toxin by H.
      pylori.
AB  - BACKGROUND: One of the features of Helicobacter pylori infection in the human
      stomach seems to be disordered gastric acid secretion. The effect of vacuolating
      toxin (VT) produced by H. pylori on gastric acid secretion was examined. METHODS:
      VT(+)(toxigenic) and VT(-)(nontoxigenic) strains of H. pylori were cultured in
      brucella broth. The culture supernatant was added to isolated parietal cells, and
      acid secretion and intracellular adenosine 3'5'-cyclic phosphate (cAMP) and Ca2+
      levels were measured with the 14C-aminopyrine (14C-AP) method, with 125I
      radioimmunoassay (RIA), and with the fura-2 fluorescence method, respectively.
      RESULTS: In the VT(+) strain a considerable inhibitory effect on 14C-AP
      accumulation was observed. However, the VT(-) strain had no significant effect on
      intracellular c-AMP and Ca2+. CONCLUSIONS: The VT(+) strain of H. pylori has an
      inhibitory effect on gastric acid secretion, whereas the VT(-) strain does not.
      This inhibitory effect was not associated with the response of second messengers.
      It is speculated that VT produced by H. pylori has a direct action on H(+)-K+
      adenosine triphosphatase in parietal cells.

PMID- 8734338
TI  - Helicobacter colonization of biopsy specimens cultured in vitro is dependent on
      both mucosal type and bacterial strain.
AB  - BACKGROUND: Colonization by Helicobacter pylori is strictly tissue-specific. We
      have previously reported on an in vitro adhesion model for pig and human gastric
      mucosa, in which biopsy specimens were successfully infected and cultured for
      72h. The aim of this study was to compare H. pylori colonization of different
      mucosae and by different Helicobacter strains. METHODS: Specimens from pig,
      rabbit, and rat antrum, pig urinary bladder, and pig duodenum were inoculated
      with two H. pylori strains and one H. mustelae strain. Four additional strains,
      including one mutant lacking flagella, were compared on pig antral specimens.
      RESULTS: The viability of all mucosae was comparable at 48h of culture. The
      percentage adhering bacteria increased with time in all mucosae, reaching 17%,
      11%, and 2% in pig, rabbit and rat antral mucosa, 11% in pig bladder, and 3% in
      duodenum at 48h. The type of H. pylori strain was a strong determinant for
      adhesion in pig antrum. Strain SVA40 had the highest adhesion; the mutant lacking
      flagella colonized very poorly. H. mustelae adhered to all types of mucosae in a
      more unspecific manner. CONCLUSIONS: On the basis of tissue viability, bacterial
      colonization, and adhesion, pig antral mucosa is clearly superior. H. pylori
      strains differ in their ability to adhere to and colonize cultured mucosa.

PMID- 8734339
TI  - Nondispersive isotope-selective infrared spectroscopy: a new analytical method
      for 13C-urea breath tests.
AB  - BACKGROUND: Currently, stable isotope techniques in breath tests using 13C
      labeled substrates are limited to a few centers equipped with expensive and
      complex isotope ratio mass spectrometry (IRMS). Although breath samples can be
      mailed to these centers, widespread application of 13C breath tests would be more
      feasible with a cheaper and more practicable analysis system at hand. METHODS: We
      therefore tested the newly developed nondispersive isotope-selective infrared
      spectrometer (NDIRS) with reference to IRMS in a clinical setting comparing the
      results of both techniques in 538 consecutive 13C-urea breath tests performed for
      the detection of Helicobacter pylori infection. RESULTS: With NDIRS five false
      positive and three false-negative results were observed; that is, the sensitivity
      of NDIRS was 98.3%, and the specificity was 98.6%. The delta over base-line
      values of both devices correlated linearly (Y = 0.87 +/- 0.01 X + 0.29 +/- 1.5; r
      = 0.95; p < 0.0001; n = 538). CONCLUSIONS: When running this large number of
      breath tests in 3 days, the NDIRS proved to be a reliable, stable, and easy-to
      operate analytical tool, which is well qualified for gastroenterologic
      application in the diagnostic routine. Both the price and the easy handling of
      NDIRS will facilitate the widespread use of the noninvasive stable isotope
      technique for 13C breath tests.

PMID- 8734340
TI  - Human galanin modulates human colonic motility in vitro. Characterization of
      structural requirements.
AB  - BACKGROUND: Human galanin (hGal) is a 30-residue non-amidated gut-brain peptide
      that shows considerable sequence divergence compared with galanin (Gal) forms of
      other species. Conflicting results have been reported with regard to the
      structural requirements for its modulatory action on gut motility. METHODS: We
      investigated the effect of human and rat Gal and substituted analogues of Gal on
      the contractility of longitudinal muscle strips of the human colon in vitro.
      RESULTS: Both hGal and rGal contracted the preparations in a concentration
      dependent and tetrodotoxin-resistant manner without difference in sensitivity.
      The NH2-terminally truncated peptides hGal (3-30) and rGal (3-29) were inactive,
      whereas the NH2-terminal fragments, hGal (1-21) and rGal (1-18), remained fully
      responsive. Single amino acid substitutions at NH2-terminal positions showed
      divergent results: substitution of Trp2 reduced significantly potency and
      efficacy, whereas substitutions at positions 1, 3, 4, or 5 did not markedly
      modify the bioactivity of Gal. Galantide, a high-affinity Gal antagonist in the
      central nervous system, is a full agonist in human colonic smooth muscle.
      CONCLUSION: The COOH-terminal part of Gal contributes mainly the receptor-binding
      affinity of the peptide, whereas the NH2-terminal region is essential for
      biologic activity.

PMID- 8734341
TI  - Gastric antral motility in functional dyspepsia. Effect of mental stress and
      cisapride.
AB  - BACKGROUND: Disordered gastric antral motor activity may be induced by mental
      stress. The effect of cisapride on these abnormalities has previously not been
      investigated. METHODS: Ten healthy subjects and 19 patients with functional
      dyspepsia (FD) and erosive prepyloric changes participated in the study. Antral
      motility was recorded with real-time ultrasonography after ingestion of 500 ml
      meat soup during i) a 4-min rest period, ii) 2.5 min of mental stress, and iii) a
      4-min recovery period. Patients and controls were studied after 3 days of
      treatment with 10 mg cisapride three times daily and placebo in a double-blind
      crossover design. RESULTS: Mean postprandial amplitude of antral contractions was
      lower in patients than controls (p < 0.001). Antral amplitude was reduced by
      mental stress in healthy persons (p < 0.001) but not in patients. Both fasting
      and postprandial antral areas were larger in FD patients than controls (p < 0.001
      and p = 0.02, respectively). Cisapride reduced the fasting (p < 0.001) and the
      postprandial (p = 0.05) antral area in the FD group but not in controls. The soup
      meal produced dyspeptic symptoms in 90% of the patients and in only 10% of the
      controls (p < 0.001). Cisapride had no significant effect on symptoms or antral
      contractions. CONCLUSIONS: Mental stress induced antral hypomotility in healthy
      subjects but not in patients with FD who had reduced motility at base line.
      Cisapride reduced the enlarged fasting and postprandial antral areas in the
      patients but had no effect on amplitudes of antral contractions or symptoms.

PMID- 8734342
TI  - The relationship between gut hormone secretion and gastric emptying in different
      phases of the migrating motor complex.
AB  - BACKGROUND: No studies are available on the relationship between the response of
      gut hormones and gastric emptying in different phases of the migrating motor
      complex. This study examined whether basal gut hormone concentrations in plasma
      before food ingestion are predictors of emptying characteristics and whether
      different hormone secretion patterns are associated with specific alterations in
      emptying rate. METHODS: Twelve healthy men were examined on two occasions: one
      with meal ingestion in phase I and the other with meal ingestion in phase II. The
      meal consisted of an omelette labelled with 99mTc followed by 150 ml water
      labelled with 111In. Plasma concentrations of gastrin, cholecystokinin, motilin,
      and peptide YY were measured in the fasting state, immediately after food
      ingestion, and at 15-min intervals in the postprandial period. RESULTS: New
      findings from the present study include a higher incremental integrated
      postprandial motilin response in phase I than in phase II (998 pmol/l*30 min (495
      to 2010) versus 210 pmol/l*30 min (-270 to 2323), p < 0.05), and a linear
      relationship between median total integrated motilin response and solid emptying
      at 120 min in phase I (Rs = 0.58; p < 0.05). Furthermore, in phase I a linear
      relationship between total integrated area of cholecystokinin and solid emptying
      at 120 min was demonstrated (Rs = 0.62; p < 0.05). CONCLUSION: The findings from
      the present investigation have to be considered in the future design of studies
      that focus on postprandial release of gastrointestinal hormones. The transition
      from phase III to phase I is a reproducible and easily recognized pressure event.
      Therefore, we recommend the use of food ingestion immediately after termination
      of duodenal phase III.

PMID- 8734343
TI  - A double-blind placebo-controlled trial with loperamide in irritable bowel
      syndrome.
AB  - BACKGROUND: Loperamide has a relaxing effect on localized and segmental large
      bowel spasms. On the basis of previously observed effects on pain and stool
      habits in patients with diarrhoea, the present trial intended to examine the
      regulating effect in an unselected cohort of patients with the irritable bowel
      syndrome (IBS). The symptoms in IBS are dependent on variations in motility
      initiated by different mechanisms. Therefore, when examining the effect of
      treatment, characterization of the patient material is important. METHODS: Ninety
      patients were included in this prospective double-blind trial comparing
      loperamide with placebo over 5 weeks. The two groups were characterized and
      compared with healthy controls (n = 33), matched by age and sex. Demographic,
      clinical, and biochemical data were recorded. RESULTS: Clinical variables and
      social and personal relationships were similar for the loperamide group (n = 35),
      the placebo group ( n = 34), the dropouts (n = 21), and controls. Somatic
      diseases and mental disturbances were increased in the patients compared with the
      controls. Throughout the 5 weeks of treatment an improved stool consistency
      (32%), reduced defecation frequency (36%), and reduced intensity of pain (30%)
      were found in the loperamide group. An increase in nightly pain was observed in
      the loperamide group. CONCLUSIONS: This trial lends support to a multifactorial
      aetiology in IBS. Treatment must be individualized with regard to both the effect
      and the risk of constipation and abdominal pain. The trial shows a benefit of
      loperamide in an unselected cohort of IBS patients with regard to stool
      frequency, stool consistency, and the overall pain intensity, but with increased
      abdominal pain during the night. It should be recommended that the patients take
      the medication in divided daily doses.

PMID- 8734344
TI  - Redefining abdominal syndromes. Results of a population-based study.
AB  - BACKGROUND: Gastroenterologists use different definitions of irritable bowel
      syndrome and upper dyspepsia, and the different definitions select different
      populations with the syndromes. The aim of the study was, in an unselected
      population, to find combinations of abdominal symptoms that occur together more
      often than can be expected by chance and thereby find statistical support for
      standard definitions of the syndromes. METHODS: A sex- and age-stratified random
      sample of 4851 Danes living in the western part of Copenhagen was interviewed
      about abdominal symptoms. Five years later an identical interview was carried out
      among the participants. RESULTS: The participation rate was 79% in the first
      study and 85% in the second. Independent of age, sex, and time, the following
      three definitions describe subjects with symptoms occurring together more often
      than could be expected by chance: 1) Subjects stating that they often experience
      both abdominal pain and distension and, additionally, either borborygmi or
      altering stool consistency. This combination occurred with a prevalence of 3.2%
      among men and 7.5% among women; 2) Subjects stating that they experience all of
      the following three symptoms: abdominal pain, heartburn, and acid regurgitation.
      This combination occurred with a prevalence of 1.3% among men and 0.8% among
      women; 3) Subjects stating that they often experience both nausea and abdominal
      pain. This combination occurred with a prevalence of 0.9% among men and 3.6%
      among women. CONCLUSIONS: It is suggested that these three definitions should be
      used as standards for irritable bowel syndrome, upper dyspepsia-heart burn type
      and upper dyspepsia-nausea type, respectively.

PMID- 8734345
TI  - Postoperative staging of gastric carcinoma. A comparison between the UICC stage
      classification and the 12th edition of the Japanese General Rules for Gastric
      Cancer Study.
AB  - BACKGROUND: The feasibility of the latest edition of the Japanese General Rules
      for Gastric Cancer Study (GRGCS) is evaluated by comparison with the TNM system.
      METHODS: In a 5-year period from 1985 to 1989, 978 patients with gastric cancer
      underwent laparotomies at the Dept. of Gastroenterological Surgery, Aichi Centre
      Centre, Japan. All the patients have now been followed up for 5 years or until
      death. These patients were retrospectively classified into appropriate clinical
      stages and residual tumour status on the basis of the GRGCS and the 4th edition
      of the TNM classification by the UICC, and survival curves for various stages and
      subgroups were evaluated. RESULTS: The GRGCS classification provided useful
      information by splitting UICC stage IV into stages IVa and IVb, and R0 into
      curabilities A and B, both subgroups showing significant differences in the
      survival curves. CONCLUSIONS: The new edition of the GRGCS can be recommended as
      a useful staging manual for gastric cancer.

PMID- 8734346
TI  - Prognostic significance of p53 expression, chromosome 17 copy number, and DNA
      ploidy in non-metastasized colorectal carcinomas (stages IB and II).
AB  - BACKGROUND AND METHODS: Paraffin-embedded tumor tissue from 101 non-metastasized
      colorectal adenocarcinomas (tumor stages IB and II--that is, pT2 and 3, pN0, M0)
      was investigated for p53 expression by immunohistology (IH) (moab DO1),
      chromosome 17 (#17) copy number by interphase cytogenetics using non-radioactive
      in situ hybridization (NISH) with a centromer-specific DNA probe (D17Z1), and DNA
      ploidy by flow cytometry (FCM). The aims of the study were 1) to test whether
      numerical #17 aberrations are involved in functional TP53 loss in locally
      confined colorectal carcinomas; 2) to search for correlations between aberrant
      p53 expression and #17 aberrations with DNA ploidy and histopathology; and 3) to
      test the prognostic significance of these factors. RESULTS: Sixty cases (59.4%)
      showed nuclear p53 expression IH (low-grade p53 accumulation (< 50%), n = 16
      (15.8%); high-grade (> or = 50%), n = 44 (43.6%)). Nish showed #17 aneusomy in
      46% of the carcinomas (34% deletions, 12% gains). In FCM analysis, 43% of the
      carcinomas were DNA non-diploid. p53 overexpression correlated statistically
      significantly with FCM non-diploidy (p = 0.013). Furthermore, #17 aneusomy also
      correlated with FCM non-diploidy (p = 0.001). However, there was no association
      between #17 status and p53 expression (IH). CONCLUSIONS: Our data suggest a role
      for the TP53 gene in the aneuploidization process. Numerical deletions of #17,
      however, were not associated with p53 immunoreactivity in the analyzed tumors.
      With regard to prognosis, the most important independent variable in stage IB/II
      colorectal carcinomas was tumor stage, followed by high-grade p53 expression of
      tumor cells; #17 aneusomy was an independent risk factor for tumor
      relapse/progression but not for survival. As alterations of the investigated
      variables were not found in all carcinomas under study, different pathogenetic
      pathways seem to exist in colorectal carcinogenesis.

PMID- 8734347
TI  - Portal hypertensive colopathy in patients with cirrhosis.
AB  - BACKGROUND: Colonic vascular ectasias and colorectal varices have been observed
      in patients with cirrhosis. However, the pathogenesis of these vascular lesions
      has not been established. METHODS: We enrolled 35 cirrhotic patients and 20
      normal controls in this study. All received colonoscopic examinations and
      measurements of plasma glucagon levels. Portal pressure measurements were
      performed in all the cirrhotic patients. RESULTS: Colonic vascular ectasias
      occurred more commonly in cirrhotic patients than in controls (17 of 35 versus 0
      of 20; p = 0.009) and more commonly in cirrhotic patients with ascites than in
      those without (15 of 24 versus 2 of 11; p = 0.038). However, the presence of
      colonic vascular ectasias was not related to the hepatic venous pressure gradient
      or plasma glucagon levels. Colorectal varices also occurred more commonly in
      cirrhotic patients than in controls (16 of 35 versus of 1 of 20; p = 0.034), but
      the hepatic venous pressure gradient, plasma glucagon levels, and severity of
      cirrhosis were not related to the presence of colorectal varices. CONCLUSIONS:
      Portal hypertension per se and increased plasma glucagon levels may not play an
      important role in the pathogenesis of colonic vascular ectasias or colorectal
      varices in patients with cirrhosis.

PMID- 8734348
TI  - Portal duplex sonography in liver cirrhosis. A useful supplement to endoscopic
      evaluation of bleeding risk of esophageal varices?
AB  - BACKGROUND: In a prospective study we investigated whether the endoscopic
      assessment of the bleeding risk of esophageal varices could be supported by
      portal duplex sonography. METHODS: Over the time span of 2.5 years (range, 13 +/-
      5 months) we observed 41 patients with liver cirrhosis. During that time 17
      patients had acute esophageal variceal hemorrhage and constituted the bleeding
      group, and the remaining 24 patients without a hemorrhage constituted the non
      bleeding group. RESULTS: Within the bleeding group the mean portal blood flow
      velocity (Vm) was 0.093 +/- 0.033 m/sec, and the mean flow volume (Fm) was 0.371
      +/- 0.173 l/min. Both results were significantly lower than the corresponding
      results of the nonbleeding group (p < 0.017; p < 0.05). By assuming cut-offs for
      Vm of 0.12 m/sec and for Fm of 0.420 l/min, we obtained a diagnostic sensitivity
      for hemorrhage of 0.88 and 0.65. CONCLUSION: Our results show that portal duplex
      sonography may improve the evaluation of endoscopically ascertained bleeding risk
      of esophageal varices.

PMID- 8734349
TI  - Plasma interleukin-6 levels in patients with cirrhosis. Relationship to
      endotoxemia, tumor necrosis factor-alpha, and hyperdynamic circulation.
AB  - BACKGROUND: Liver cirrhosis with portal hypertension is associated with
      hyperdynamic circulation characterized by generalized vasodilatation and
      increased cardiac output and regional blood flows. Patients with liver cirrhosis
      present with increased levels of interleukin-6 (IL-6), which may inhibit vascular
      smooth-muscle contraction. We investigated whether increased plasma IL-6 levels
      contribute to the pathogenesis of hyperdynamic circulation observed in cirrhotic
      patients and whether they are correlated with plasma tumor necrosis factor-alpha
      (TNF-alpha) and endotoxin concentrations. METHODS: In 58 consecutive cirrhotic
      patients and 34 healthy subjects the plasma concentrations of TNF-alpha and IL-6
      were measured with enzyme-linked immunosorbent assay, and endotoxin
      determinations with a limulus assay. In addition, 52 cirrhotic patients underwent
      a hemodynamic study using Swan-Ganz catheterization. RESULTS: Plasma TNF-alpha,
      IL-6, and endotoxin levels were significantly higher in cirrhotic patients than
      in healthy subjects (7.3 +/- 0.2 versus 5.8 +/- 0.1 pg/ml, 6.4 +/ 0.8 versus 2.0
      +/- 0.2 pg/ml, and 7.6 +/- 1.2 versus 2.8 +/- 0.3 pg/ml, respectively; p < 0.01).
      In cirrhotic patients the plasma levels of TNF-alpha IL-6, and endotoxin
      progressively increased in relation to the severity of liver dysfunction (graded
      by Pugh's classification). A significant correlation was observed between plasma
      TNF-alpha and IL-6 levels (r = 0.48, p < 0.001), whereas no correlation was
      observed between plasma endotoxin levels and plasma TNF-alpha and IL-6 levels.
      Plasma IL-6 levels correlated negatively with systemic vascular resistance in
      patients with cirrhosis (r = 0.5, p < 0.01). CONCLUSIONS: Plasma IL-6 levels are
      increased in patients with cirrhosis. The severity of liver cirrhosis is an
      important factor for the occurrence of increased IL-6 levels. IL-6 may play a
      role in the hyperdynamic circulation observed in patients with cirrhosis.

PMID- 8734350
TI  - Biliary complications in one hundred adult liver transplantations.
AB  - BACKGROUND: Biliary complications are a common problem in liver transplantation
      (LT). METHODS: We reviewed 100 consecutive adult LTs, including 10
      retransplantations. Ten patients who survived for less than 1 month or developed
      hepatic artery thrombosis were excluded. Biliobiliary anastomosis was performed
      with a T-tube (CCT) (n = 25) or without it (CC) (n = 59), or biliodigestive
      anastomosis (Rouxen-Y) (n = 6) was used. RESULTS: Biliary complications (8
      anastomotic strictures and 9 bile leakages) occurred in 15 LTs. Surgical
      treatment was needed for seven strictures and two leakages. Complications tended
      to be more frequent with CCT than with CC (24% versus 12%). Biliary complications
      were often accompanied by cytomegalovirus disease and bacterial infections. After
      a median follow-up time of 5.2 years, total patient survival was 71% for all 100
      LTs and 81% for those with biliary complications. CONCLUSIONS: Biliary
      complications are rather frequent after LTs; they are often preceded by
      infections but can be treated and do not cause excessive mortality. T-tubes are
      not to be recommended.

PMID- 8734351
TI  - Acute effect of ursodeoxycholic acid on gallbladder volume in healthy subjects.
AB  - BACKGROUND: Although it has been shown that chronic administration of
      ursodeoxycholic acid increases gallbladder fasting and residual volume, it is
      unknown whether ursodeoxycholic acid exerts an acute effect on gallbladder
      volume. We therefore evaluated the effect of a single oral dose of
      ursodeoxycholic acid on gallbladder volume in healthy volunteers. METHODS: After
      the volunteers had fasted overnight, gallbladder volume was measured
      sonographically every 15 min for 5 h. Following a 1-h control period group I (n =
      8) received ursodeoxycholic acid (1000 mg) orally with 100 ml of water, whereas
      group II (n = 8) received 100 ml of water (placebo) only. Gallbladder volumes
      were calculated, applying the sum-of-cylinders method. Serum levels of
      ursodeoxycholic acid were determined by gas chromatography at 1-h intervals.
      RESULTS: Gallbladder fasting volumes before ursodeoxycholic acid were similar in
      both groups (24.0 +/- 2.3 ml versus 25.4 +/- 3.3 ml; NS). After ingestion of
      ursodeoxycholic acid (group I) gallbladder volume increased rapidly, reaching
      27.6 +/- 3.1 ml (p < 0.04) 1 h and 38.4 +/- 3.4 ml (p < 0.02) 4 h after ingestion
      of ursodeoxycholic acid. The individual gallbladder volumes after ingestion of
      ursodeoxycholic acid in group I increased to 146%-211% of pretreatment values.
      Ursodeoxycholic acid serum levels increased from 0.94 +/- 0.38 mumol/l to 10.51
      +/- 1.36 mumol/l (p < 0.001) and correlated closely with gallbladder volumes (r =
      0.80; p < 0.05). After ingestion of water only (group II) gallbladder volume
      decreased transiently from 15 min to 30 min after water intake and then remained
      at pretreatment values throughout the study period. CONCLUSION: Administration of
      a single oral dose of ursodeoxycholic acid causes a rapid increase in gallbladder
      volume, which reaches 163 +/- 10% of pretreatment volume at 4 h and is closely
      correlated with ursodeoxycholic acid serum levels.

PMID- 8734352
TI  - Pancreatic duct abnormalities and pancreatic function in patients with chronic
      inflammatory bowel disease.
AB  - BACKGROUND: We performed a cross-sectional study to estimate the prevalence of
      duct abnormalities and exocrine pancreatic dysfunction in an unselected group of
      patients with inflammatory bowel disease (IBD) and to correlated the findings
      with clinical, endoscopic, and histologic variables. METHODS: A total of 237 IBD
      patients were screened for pancreatic enzymes and with a PABA test. Seventy-one
      (30%) patients with values more than twice the upper normal limit in biochemical
      tests or with a PABA test < 40% were further evaluated. The pancreatic evaluation
      included endoscopic retrograde pancreatography, ultrasonography, and a secretin
      test. The endoscopic and histologic findings were systematically evaluated.
      RESULTS: The secretin test was completed in 54 patients, and in 10 (19%) it
      showed a decreased maximal bicarbonate concentration, corresponding to 4% of the
      whole study group. The pancreatograms of 59 patients were studied. In 20 (34%)
      patients unequivocal duct abnormalities were found. The prevalence of pancreatic
      duct abnormalities in IBD was 8.4%. CONCLUSION: Our results show the presence of
      pancreatic duct abnormalities and exocrine pancreatic insufficiency in some
      patients with IBD.

PMID- 8734354
TI  - Serum gastrin levels.

PMID- 8734353
TI  - Giant splenic cyst with high serum concentration of CA 19-9. Failure of treatment
      with percutaneous transcatheter drainage and injection of tetracycline.
AB  - BACKGROUND: Recently, several cases of nonparasitic true splenic cyst with high
      serum concentration of carbohydrate antigen (CA 19-9) have been reported. CASE:
      We report a giant splenic cyst presenting with high serum concentration of CA 19
      9 in a 21-year-old man without a history of previous trauma. Imaging techniques
      showed a huge monolocular cyst of the spleen, and laboratory data showed
      increased serum CA 19-9 levels (326 U/ml; normal, < 37 U/ml). Serologic test was
      negative for parasitic infection. These findings led us to the diagnosis of
      epithelial splenic cyst. Percutaneous transcatheter drainage and injection of
      tetracycline were performed for 2 weeks. The cyst shrank, and the serum CA 19-9
      level decreased favorably. However, cystic fluid reaccumulated in a month.
      CONCLUSIONS: The accumulation of cystic fluid in splenic epithelial cysts may be
      attributable not only to the secretion of the lining cells but also to influx
      from the splenic sinuses.

PMID- 8734355
TI  - Progress and challenges toward an AIDS vaccine: Brother, can you spare a
      paradigm?
AB  - The development of a safe and effective vaccine for prevention of AIDS has thus
      far proven to be exceedingly difficult due to the complexities associated with
      HIV pathogenesis including but not limited to antigenic hypervariability,
      multiple routes and modes of transmission, a lack of defined correlates of
      protective immunity, and a tropism for infection of immunoregulatory cells which
      are essential for orchestrating an effective host immune response. Recent
      observations, including the identification of significant differences between
      primary isolates of HIV circulating in the population and laboratory-adapted
      isolates, animal model protection studies demonstrating prevention of AIDS-like
      disease progression in nonhuman primates in the absence of sterilizing immunity,
      and epidemiologic studies which question the current dogma surrounding HIV
      variation and control, have led to the development of novel approaches for
      antigen presentation and adjuvant development targeted at AIDS vaccine
      development. The goal of developing a safe and effective AIDS vaccine will likely
      occur when continued advances in understanding the immunopathogenesis of HIV is
      balanced with a healthy dose of empirical testing of innovative candidate AIDS
      vaccines.

PMID- 8734356
TI  - Characterization of interleukin-15 (IL-15) and the IL-15 receptor complex.
AB  - IL-15 interacts with a heterotrimeric receptor that consists of the beta and
      gamma subunits of the IL-2 receptor (IL-2R) as well as a specific, high-affinity
      IL-15-binding subunit, which is designated IL-15R alpha. Since both the beta and
      the gamma subunits of the IL-2R are required for signaling by either IL-2 or IL
      15, it is not surprising that these cytokines share many activities in vitro.
      However, the differential expression of these cytokines and the alpha chains of
      their receptors within various tissues and cell types suggests that IL-2 and IL
      15 may perform at least partially distinct physiological functions. The
      production of IL-15 by macrophages, and possibly other cell types, in response to
      environmental stimuli and infectious agents suggests that IL-15 may play a role
      in protective immune responses, allograft rejection, and the pathogenesis of
      autoimmune diseases.

PMID- 8734357
TI  - Mucosal inflammatory cytokine production by intestinal biopsies in patients with
      ulcerative colitis and Crohn's disease.
AB  - Chronic inflammation in inflammatory bowel disease (IBD; Crohn's disease and
      ulcerative colitis) may be attributed partly to increased secretion of
      inflammatory cytokines. The aim of this study was to investigate simultaneously
      the spontaneous release patterns of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1-beta (IL-1 beta), and interleukin-6 (IL-6) by organ cultures of
      inflamed mucosa from IBD patients. Organ cultures of involved IBD mucosa
      spontaneously produced increased amounts of TNF-alpha, IL-1 beta, and IL-6
      compared to normal mucosa. The patterns of cytokine release between Crohn's
      disease and ulcerative colitis organ cultures were not significantly different.
      Increased inflammatory cytokine production by lamina propria mononuclear cells
      (LPMCs) and mucosa treated with EDTA suggests that these cytokines originate
      mainly from LPMCs. These results confirm the role of inflammatory cytokines in
      IBD and shed a new light on the role of TNF-alpha in IBD.

PMID- 8734358
TI  - Abnormal in vitro thymocyte differentiation in a patient with severe combined
      immunodeficiency-Nezelof's syndrome.
AB  - An in vitro coculture model system of CD34+ stem cells and allogenic cultured
      thymic epithelia fragments was used to evaluate thymocyte differentiation in a 9
      month-old child of Amish descent with Nezelof syndrome. Though the patient's stem
      cells differentiate to acquire normal expression of CD2 and CD7, later steps of
      maturation were abnormal. There was detectable but reduced expression of CD3 and
      CD4 phenotypes. CD44+ expression, however, was markedly reduced. CD44 is an
      adhesion molecule, interacting with the matrix ligands hyaluronan and
      fibronectin, and is expressed early in thymocyte differentiation and subsequently
      in mature T cells. It is hypothesized that abnormal expression of CD44 in a
      variant of severe combined immunodeficiency, Nezelof's syndrome, interferes with
      normal thymocyte and thymic epithelial interaction, which leads to abnormal
      thymocyte differentiation.

PMID- 8734359
TI  - Blood cytokine levels rise even after minor surgical trauma.
AB  - The exact changes in cytokine production and clinical implications of the
      increased cytokine levels following operative trauma remain unclear. In this
      study, systemic production of a spectrum of cytokines, including IL1 alpha, IL1
      beta, IL6, IL8, IL10, and IFN gamma, was examined in patients undergoing minor
      elective operative trauma. The levels of IL1 receptor antagonist (ra) and IL6
      soluble receptor (sR) were also determined. Although there were no changes in IL1
      alpha and IL1 beta plasma levels during the entire observation period, there was
      a significant rise in IL1 ra level in all patients between postoperative day 1
      and postoperative day 14. A significant increase in the IL6 plasma level was seen
      on days 1, 3, and 7 after surgery and an increase in the IL6 sR level was
      observed on postoperative days 10 and 14. Interestingly, the IL8 plasma values
      had risen significantly on days 1 and 3 following the operation. In some
      patients, an elevation in IL10 plasma level was noted on days 1 and 3
      postsurgery. Results demonstrated that even a minor surgical procedure such as
      cholecystectomy with uneventful wound healing was followed by an appearance in
      the blood circulation of significant levels of cytokines between day 1 and day 14
      after surgery. These observations point to the necessity of searching for methods
      of down-regulating the systemic cytokine effects after surgical trauma for the
      routine postoperative management.

PMID- 8734360
TI  - Long-term follow-up of health in blood donors with primary selective IgA
      deficiency.
AB  - A 20-year health follow-up study of 159 initially healthy blood donors with a
      severe deficiency of serum IgA ( < 0.05 x 10(-3) g/L) and of 45 donors with
      decreased serum IgA (0.05 x 10(-3)-0.8 g/L) was carried out. The findings
      indicate that persons with a severe deficiency of and decreased serum IgA who are
      healthy as young adults have an increased susceptibility to pneumonia and
      recurrent episodes of other respiratory infections and a higher risk of
      developing autoimmune diseases in middle age. Vitiligo, autoimmune hypothyreosis,
      milk intolerance, and possible rheumatoid arthritis were associated with severe
      IgA deficiency, but otherwise different degrees of IgA deficiency seem to be
      similar with respect to the appearance of diseases. Regardless of the fact that a
      total of 163 (80%) of the 204 IgA-deficient subjects had-episodes of infections,
      drug allergy, or autoimmune or atopic disease, the finding of primary, selective
      IgA deficiency in a healthy adult per se does not seem to predict severe life
      threatening illnesses at least during 20 years of life.

PMID- 8734361
TI  - The effects of retinoic acid on immunoglobulin synthesis: role of interleukin 6.
AB  - Retinoic acid (RA) and its parent compound, retinol (ROH, vitamin A), have been
      recognized as important immunopotentiating agents. Previous studies from our
      laboratory have demonstrated that RA can augment formalin-treated Staphylococcus
      aureus (SAC)-stimulated immunoglobulin (Ig) synthesis of cord blood mononuclear
      cells (CBMC). To determine the mechanism(s) by which RA modulates Ig synthesis,
      we studied the effects of RA on B cells and cytokine production. The addition of
      RA (10(-5) to 10(-10) M) to Epstein-Barr virus (EBV)-transformed B-cell clones
      derived from either adult or cord blood B cells augmented Ig secretion twofold.
      In contrast, cell proliferation was inhibited as measured by 3H-thymidine
      incorporation. We evaluated two cytokines known to be constitutively produced by
      EBV cell lines, IL-1 and IL-6. While RA had no effect on IL-1 production, IL-6
      synthesis was greatly enhanced (20- to 45-fold), which was also reflected by an
      increase in steady-state mRNA levels for IL-6 but not TNF-alpha or TGF-beta on
      Northern blot analysis. Polyclonal rabbit anti-IL-6 antibodies were used to block
      the augmenting effects of RA on Ig synthesis of adenoidal B cells. RA-induced
      augmentation in IgG and IgA synthesis was blocked 58 and 29%, respectively, by
      anti-IL-6 antibodies. These studies suggest that the enhancing effects of RA on
      Ig synthesis are mediated, at least in part, by the autocrine or paracrine
      effects of IL-6 on B-cell differentiation.

PMID- 8734362
TI  - [Consensus conference: "Ulcer and gastritis at the time of Helicobacter pylori".
      Why and how?].

PMID- 8734363
TI  - [Gastroduodenal ulcer disease and gastritis: general epidemiology, natural
      history and progression].

PMID- 8734364
TI  - [Chronic gastritis and gastroduodenal ulcers: anatomopathological aspects, course
      and progression].

PMID- 8734365
TI  - [Role of acid secretion in the pathogenesis of duodenal ulcer].

PMID- 8734366
TI  - [Role of Helicobacter pylori in the pathogenesis of ulcer disease and gastritis].

PMID- 8734367
TI  - [Epidemiology of Helicobacter pylori: disparities in the distribution of the
      infection].

PMID- 8734368
TI  - [When to look for Helicobacter pylori?].

PMID- 8734369
TI  - [How to look for Helicobacter pylori?].

PMID- 8734370
TI  - [How to eradicate Helicobacter pylori in 1995? Critical review of available
      treatments].

PMID- 8734371
TI  - [Therapeutic management of duodenal ulcer except in emergency cases:
      antisecretory treatment].

PMID- 8734372
TI  - [Therapeutic management of duodenal ulcer except in emergency: eradication of
      Helicobacter pylori].

PMID- 8734373
TI  - [Management of duodenal ulcer except in emergency: surgical treatment].

PMID- 8734374
TI  - [Medical treatment of stomach ulcer except in emergency].

PMID- 8734375
TI  - [Management of stomach ulcer except in emergency: surgical treatment].

PMID- 8734376
TI  - [Helicobacter pylori infection: relationships between gastritis and clinical
      symptomatology].

PMID- 8734377
TI  - [When should Helicobacter pylori be eradicated?].

PMID- 8734378
TI  - [Role of Helicobacter infection in the causes and mechanisms of gastroduodenal
      ulcer and chronic gastritis].

PMID- 8734379
TI  - [Diagnostic methods of Helicobacter pylori infection].

PMID- 8734380
TI  - [How to eradicate Helicobacter pylori?].

PMID- 8734381
TI  - [What is the right therapeutic management of duodenal ulcer except in
      emergency?].

PMID- 8734382
TI  - [Treatment of stomach ulcer].

PMID- 8734383
TI  - [Should Helicobacter pylori be eradicated in a patient with chronic gastritis?].

PMID- 8734384
TI  - [Ulcer disease and gastritis in Helicobacter pylori infection].

PMID- 8734385
TI  - [Ulcer disease and gastritis in Helicobacter pylori infection].

PMID- 8734386
TI  - The odyssey of Orpheus: the evolution of solo singing.
AB  - Notated sacred solo song dates from 1,000 B.C. Early secular song exhibits modest
      vocal demands of chant-like character. Popular song and liturgical solo song
      share common origins. Western European secular song notation began in the early
      Medieval Age. Compositional writing for solo voice took a dramatic turn toward
      virtuosity about 1600. By the mid-17th century, the modern solo voice emerged.
      "Classical" solo vocal literature is not static but is constantly evolving,
      requiring skills far in excess of those of speech or of early solo song
      literature; this is equally the case with ethnomusicological and popular singing
      styles. Efficient use of the singing instrument is essential to the healthy
      accomplishment of all of these literatures.

PMID- 8734387
TI  - Bifurcations in excised larynx experiments.
AB  - Bifurcation analysis was applied to vocal fold vibration in excised larynx
      experiments. Phonation onset and vocal instabilities were studied in a parameter
      plane spanned by subglottal pressure and asymmetry of either vocal fold adduction
      or elongation. Various phonatory regimes were observed, including single vocal
      fold oscillations. Selected spectra demonstrated correspondence between these
      regimes and vocal registers noted in the literature. To illustrate the regions
      spanned by the various phonatory regimes, two-dimensional bifurcation diagrams
      were generated. Many instabilities or bifurcations were noted in the regions of
      coexistence, i.e., regions in which the phonatory regimes overlap. Bifurcations
      were illustrated with spectrograms and fundamental frequency contours. Where
      possible, results from these studies were related to clinical observations.

PMID- 8734388
TI  - Respiratory and glottal efficiency measures in normal classically trained
      singers.
AB  - Respiratory and glottal efficiency measures were collected from a pool of 40
      classically trained singers with normal larynges. All singers had > or = 3 years
      of formal classical voice training and were active professional solo classical
      singers. Mean flow rates were obtained from all subjects to assess glottal
      efficiency. Additionally, maximum phonation times and phonation quotients were
      obtained from a subset of the singers. Pulmonary function test data on forced
      expiratory volume, forced vital capacity, and forced expiratory flow were
      obtained for all subjects. Results were compared with published normal values,
      not specifically derived from trained singers, used commonly in voice
      laboratories. Differences were found, suggesting the need for separate normative
      data to be used for evaluation of the vocal athlete.

PMID- 8734389
TI  - Objective measures of voice production in patients complaining of laryngeal
      fatigue.
AB  - The purpose of this retrospective study is to describe results of acoustic,
      aerodynamic, and videostroboscopic measures in patients complaining of laryngeal
      fatigue. Data were collected from 88 patients whose primary complaint was chronic
      laryngeal fatigue in the absence of visible laryngeal pathologies. The results
      revealed an abnormally high airflow rate and decreased maximum phonation time. An
      anterior glottal chink, anterior and posterior glottal chinks, or spindle-shaped
      glottal closure were found in 61% of the subjects.

PMID- 8734390
TI  - Perceived pitch of whispered vowels--relationship with formant frequencies: a
      preliminary study.
AB  - To clarify the role of formant frequency in the perception of pitch in
      whispering, we conducted a preliminary experiment to determine (1.) whether
      speakers change their pitch during whispering; (2.) whether listeners can
      perceive differences in pitch; and (3.) what the acoustical features are when
      speakers change their pitch. The listening test of whispered Japanese speech
      demonstrates that one can determine the perceived pitch of vowel /a/ as ordinary,
      high, or low. Acoustical analysis revealed that the perception of pitch
      corresponds to some formant frequencies. Further data with synthesized whispered
      voice are necessary to confirm the importance of the formant frequencies in
      detail for perceived pitch of whispered vowels.

PMID- 8734391
TI  - Comparison of various automatic means for measuring mean fundamental frequency.
AB  - The purpose of this paper was to evaluate the reliability of, and agreement
      among, six speech analysis systems in the determination of fundamental frequency.
      Five male and five female speakers provided oral reading and sustained vowel
      samples for analysis. Each sample was analyzed five times by each system. The
      results indicated high reliability for all of the systems for both sexes and both
      utterance types. Agreement among the systems was high for the male sustained
      vowels and the female oral reading samples. In contrast, poor agreement occurred
      among the systems for the male oral reading samples and the female sustained
      vowels. The findings indicate that the output of these automatic methods tends to
      be consistent over repeated trials within the systems in their extraction of
      fundamental frequency; however, agreement among these systems varies.

PMID- 8734392
TI  - Intrasubject variability of objective voice measures.
AB  - Recent advances in the diagnosis and treatment of voice disorders necessitate the
      need for accurate and reliable objective voice measurements. There are many
      instruments commonly used to analyze voice data. Many, if not most, of these
      instruments have not been adequately tested for reliability or consistency. This
      study evaluates the intrasubject variability of the objective voice measurements
      from two commonly used voice analysis instruments. The study also presents data
      correlating subjective mood states, room temperatures, sleep times of the
      subject, time since last meal, and hydration levels to the various acoustic
      measures. Several weak but significant correlations were obtained and are
      discussed. Guidelines for the appropriate use of these instruments are described.

PMID- 8734393
TI  - Standardized laryngeal videostroboscopic rating: differences between untrained
      and trained male and female subjects, and effects of varying sound intensity,
      fundamental frequency, and age.
AB  - To determine the influence of the factors gender, vocal training, sound
      intensity, pitch, and aging on vocal function, videolaryngostroboscopic images of
      214 subjects, subdivided according to gender and status of vocal training, were
      evaluated by three judges with standardized rating scales, comprising aspects of
      laryngeal appearance (larynx/pharynx ratio; epiglottal shape; asymmetry arytenoid
      region; compensatory adjustments; thickness, width, length, and elasticity of
      vocal folds) and glottal functioning (amplitudes of excursion; duration,
      percentage, and type of vocal fold closure; phase differences; location of
      glottal chink). The video registrations were made while the subjects performed a
      set of phonatory tasks, comprising the utterance of the vowel /i/ at three levels
      of both fundamental frequency and sound intensity. Analysis of the rating scales
      showed generally sufficient agreement among judges. With the exception of more
      frequently observed complete closure and lateral phase differences of vocal fold
      excursions in trained subjects, no further differences were established between
      untrained and trained subjects. With an alpha level of p = 0.005, men differed
      from women with respect to laryngeal appearance (larynx/pharynx ratio,
      compensatory adjustments, and the presence of omega and deviant-shaped
      epiglottises), and their vocal folds were rated thicker in the vertical
      dimension, smaller in the lateral dimension, longer, and more tense, with smaller
      amplitudes of excursion during vibration. Glottal closure in male subjects was
      rated more complete, but briefer in duration. Significant effects of the factors
      pitch, sound intensity, and age on vocal fold appearance and glottal functioning
      were ascertained. Awareness of the influence of these factors, as well as the
      factor gender, on the rated scales is essential for an adequate evaluation of
      laryngostroboscopic images.

PMID- 8734394
TI  - The sound of senescence.
AB  - This paper draws together findings of recent studies examining changes in voice
      with aging. Listeners' accuracy in perceiving age from voice is discussed, along
      with changes in speaking fundamental frequency, fundamental frequency stability,
      temporal aspects of speech, and resonance features of voice with aging.
      Descriptions are provided of differences in glottal gap configuration as a
      function of age and gender. In addition, acoustic/temporal measures that have
      been demonstrated to correlate with perceived age estimates are presented.

PMID- 8734395
TI  - Videokymography: high-speed line scanning of vocal fold vibration.
AB  - A digital technique for high-speed visualization of vibration, called
      videokymography, was developed and applied to the vocal folds. The system uses a
      modified video camera able to work in two modes: high-speed (nearly 8,000
      images/s) and standard (50 images/s in CCIR norm). In the high-speed mode, the
      camera selects one active horizontal line (transverse to the glottis) from the
      whole laryngeal image. The successive line images are presented in real time on a
      commercial TV monitor, filling each video frame from top to bottom. The system
      makes it possible to observe left-right asymmetries, open quotient, propagation
      of mucosal waves, movement of the upper and, in the closing phase, the lower
      margins of the vocal folds, etc. The technique is suitable for further processing
      and quantification of recorded vibration.

PMID- 8734396
TI  - Superior laryngeal nerve paresis and paralysis.
AB  - Superior laryngeal nerve paresis and paralysis are relatively common but often
      difficult to diagnose with certainty. They are most commonly caused by viral
      infections, though other etiologies must be considered. A thorough history and
      physical examination, including strobovideolaryngoscopy and laryngeal
      electromyography, are needed for definitive diagnosis. It is essential to
      establish the diagnosis accurately to differentiate an apparent superior
      laryngeal nerve paresis from other conditions, such as myasthenia gravis.
      Laryngeal electromyography is used to confirm clinical impressions, as a guide
      for therapy, and as one measure of recovery. In our experience, accurate and
      early diagnosis assure the best phonatory outcome by directing therapy that will
      prevent or eliminate compensatory vocal abuses, which may themselves lead to even
      more serious vocal injury.

PMID- 8734397
TI  - Three-dimensional head kinematics and cervical range of motion in the diagnosis
      of patients with neck trauma.
AB  - OBJECTIVE: To create a statistical model using three-dimensional (3D) head
      kinematics and range of motion (ROM) to distinguish between people with whiplash
      syndrome and asymptomatic controls. STUDY DESIGN: Cross-sectional study to
      estimate validity of diagnostic measures. METHODS: Fifty-one asymptomatic
      controls (most of whom were women), 18-35 yr old and 30 matched whiplash trauma
      patients seeking care from suburban outpatient clinics were sought. 3D kinematic
      parameters of head motion were obtained during tracking tasks (e.g., flexion,
      extension, etc.) and cervical ROM was measured via a head mounted inclinometer.
      Their level of pain and disability was assessed via a self-administered neck
      disability index questionnaire and visual analog pain scale (VAS). RESULTS: A
      scoring system of biomechanical abnormalities derived from the vertical piercing
      point, its second derivative and symmetry during oblique tasks. The scores ranged
      from a minimum of 0 to a maximum of 3. A cutoff of > or = 0.5 correctly
      identified the greatest number of subjects and minimized false positives
      (sensitivity 77%, specificity 82%, likelihood ratio 4.5). ROM performed similarly
      well at a cutoff of 1 SD below the normative mean (sensitivity 77%, specificity
      84%, likelihood ratio 3.9). CONCLUSIONS: There is potential for biomechanical
      analysis to objectively detect abnormalities. The statistical model yielded
      moderate to high sensitivity and specificity using 3D helical-axis parameters of
      the head and standard ROM. The model development will continue via this process
      in future studies. These data could be a first step toward the creation of
      useful, noninvasive protocols for the diagnosis and management of soft tissue
      trauma of the neck.

PMID- 8734398
TI  - Oscillations of the vertebrae in spinal manipulative therapy.
AB  - OBJECTIVE: To determine the general nature of the biomechanical response of the
      vertebrae to small forces, such as spinal manipulative therapy (SMT). DESIGN:
      Perturbation theoretical methods of physics and mechanical energy considerations
      are used to derive the equations of motion of the vertebral bodies moving under
      the combined influences of ligamentous and discogenic forces, applied forces and
      dissipative forces attributable to surrounding tissues. RESULTS: The allowable
      solutions to the equations of motion determine that the mechanical response of
      any vertebra to SMT should consist of a superposition of damped oscillations.
      This is based on the most general assumptions about the spine that are consistent
      with clinical observations, namely, that patients can lie stably motionless, and
      is independent of the specifics of any spinal model. DISCUSSION: The extant data
      are shown to be consistent with this theory. The implications for future research
      and clinical practice are explored. CONCLUSIONS: Vertebral motion in response to
      SMT seems to occur in two distinct phases: an initial, (passive) oscillatory
      response to the SMT thrust, governed by ligamentous and discogenic forces, and a
      later, less regular motion, probably caused by muscular reflex contractions.
      Evidence of this includes direct measurement of oscillations, surface
      electromyogram measurements of muscle responses and detection of multiple spinal
      resonances. Further research on the muscular reflex responses to SMT is
      necessary. Most SMT should initiate some of the normal-mode oscillations of the
      vertebrae. There may be up to 144 different frequencies of vertebral oscillatory
      motion in each individual in any posture; those frequencies detected thus far are
      consistent with the predicted relationship between frequencies, vertebral body
      masses and coefficients of stiffness. Further data are needed to confirm the
      detailed validity of this theory.

PMID- 8734399
TI  - The role of congruence between patient and therapist in chronic low back pain
      patients.
AB  - OBJECTIVE: To determine the role of congruence in the perception of the evolution
      of back pain during treatment and in the expectations about the future of back
      pain problems. Congruence was defined as the agreement between patient and
      therapist on various aspects of back pain problems and of treatment. DESIGN:
      Semistructured interviews at the beginning and the end of treatment. SUBJECTS:
      Seventy-one back pain patients and their therapists (6 chiropractors and 6
      rheumatologists). MAIN OUTCOME MEASURES: Synthesized index of congruence based on
      24 questions asked of both the patient and his/her therapist. RESULTS: The
      distribution of the congruence scores indicated a high level of congruence in
      39.4% of the cases, an average level in 35.2% and a low level in 25.4%. The
      results demonstrated that congruence was significantly associated with the
      perception of an improvement in back pain. This positive perception was
      nevertheless associated with the expectation of persistence or recurrence of the
      back pain problem in the future. Noncongruence was correlated with the patient's
      estimation of a less favorable evolution of the back pain problem during the
      treatment and with a major difficulty for both the therapist and the patient to
      express clear expectations about the future of the patient's back pain problem.
      CONCLUSIONS: Congruence mainly reflects an agreement that the treatment is aimed
      at the management of a long-term condition rather than at the resolution of the
      back pain problem. Congruent patients seem to accept living with their back
      problems, a position shared by their therapists, whereas noncongruent patients do
      not seem to share this conception of back pain.

PMID- 8734400
TI  - Stiffness judgments are affected by visual occlusion.
AB  - OBJECTIVE: The current protocol for judging posteroanterior (PA) spinal stiffness
      has been shown to provide unreliable estimates of PA stiffness. It is possible
      that a failure to standardize therapists' use of vision in the test protocol
      partly contributes to the disagreement between raters. This study sought to
      establish whether vision affects stiffness judgments and so needs to be
      standardized when judging PA stiffness. DESIGN: Perceptual study using a
      mechanical device to provide stiffness stimuli with physiotherapists and lay
      people as judges. SETTING: University psychophysics laboratory. INTERVENTIONS:
      Occlusion of vision via opaque goggles. MAIN OUTCOME MEASURES: Measures of
      interstimulus discriminability and bias. RESULTS: Occluding vision had no effect
      on judges' ability to discriminate between stiffness stimuli; however, the same
      stimuli were judged as significantly stiffer under the visual occlusion
      condition. CONCLUSION: The data from this study suggest that vision needs to be
      controlled when using manual tests to judge PA spinal stiffness.

PMID- 8734401
TI  - The impact of health policy on chiropractic.
AB  - OBJECTIVE: The chiropractic profession has traditionally had little or no direct
      influence on health policy. Conversely, every chiropractor is impacted daily by
      health policy decisions promulgated by government agencies, health purchasers,
      managed care organizations and others. This discussion provides an overview of
      health policy constituencies important to chiropractors, reviews processes
      currently being used to assess health care technology and develop policy and
      offers strategies for the profession to more actively engage in constructive
      policy development. METHOD: Descriptive overview of key issues based on
      qualitative selective overview of literature and author's observations based on
      two years employment in a government health policy position. CONCLUSIONS: The
      chiropractic profession's traditional approach to influencing health policy has
      focused on public relations, political lobbying for favorable legislation and
      litigation, which has increased public awareness and resulted in a number of
      legislative successes. However, for the most part, the momentum of decision
      making at agency levels and in policy staff positions continues to occur without
      involvement of chiropractors trained or experienced in policy-making. This is in
      contrast with medicine and other allied health fields, whose ranks hold such
      positions routinely. Additionally, methodology for policy decision-making is
      increasingly evidence-based. Strategies for the chiropractic profession to more
      actively participate in this arena are offered.

PMID- 8734402
TI  - Tethered cord syndrome.
AB  - OBJECTIVE: To briefly discuss a case of tethered spinal cord syndrome, and to
      acquaint the reader with one of many important differential considerations among
      patients presenting with low back and leg pain. FEATURES: A 32-yr-old woman
      sought treatment at a private chiropractic clinic for a 6-month history of low
      back pain with intermittent diffuse bilateral leg pain and numbness. Plain films
      of the lumbar spine revealed no abnormality. Magnetic resonance imaging
      demonstrated a tethered spinal cord. INTERVENTION: The abbreviated filum
      terminale was surgically corrected. CONCLUSIONS: Tethered cord syndrome, a
      significant finding, is likely to have been responsible for the patient's signs
      and symptoms. Magnetic resonance imaging is particularly helpful in evaluating
      spinal cord deformity, and may provide important information on patients not
      responding to chiropractic care.

PMID- 8734403
TI  - Chiropractic correction of atlantoaxial rotatory fixation.
AB  - OBJECTIVE: To discuss the diagnosis, management and possible mechanism of
      atlantoaxial rotatory fixation. CLINICAL FEATURES: An 11-yr-old girl with
      significant head tilt of 7 months' duration sought chiropractic evaluation. Her
      history included indirect head and neck trauma from a motor vehicle accident and
      prior manipulative and therapeutic treatment. There was minimal muscular
      hypertonicity, except for the sternocleidomastoid muscle on the side opposite
      head tilt. The head seemed to be locked in a classic "cock robin" position.
      Radiological examination revealed asymmetry of the atlanto-odontoid interval,
      suggesting occipital-atlantoaxial joint dysfunction. A diagnosis of atlantoaxial
      rotatory fixation was made. INTERVENTION AND OUTCOME: Treatment included
      vectored/linear, upper cervical, high-velocity, low-amplitude chiropractic
      manipulation of the atlas vertebra, mobilizing manipulation and stretching
      exercises. Complete resolution occurred. CONCLUSION: This single case study
      suggests that chiropractic manipulation may be a viable treatment option for
      atlantoaxial rotatory fixation. Further investigation into manipulation as a
      treatment should be pursued.

PMID- 8734404
TI  - Chiropractic and the information superhighway: a brief guide to the Internet.

PMID- 8734405
TI  - Misuse of the literature by medical authors in discussing spinal manipulative
      therapy injury.

PMID- 8734406
TI  - Where do we go from here?

PMID- 8734407
TI  - Attitudes on immunization: a survey of American chiropractors.

PMID- 8734408
TI  - Manipulation and cervicogenic headache.

PMID- 8734409
TI  - Extinction of peroxisomal functions in hepatoma cell-fibroblast hybrids.
AB  - Although peroxisomes are ubiquitous, differences in the number of organelles and
      in the expression of associated metabolic activities are observed, depending on
      the cell type. To investigate the control of peroxisomal activity in connection
      with cell differentiation, we constructed hybrids between two types of cells
      whose histogenetic origins dictate significant differences in peroxisomal
      activities: hepatoma cells and fibroblasts, with high and low expression,
      respectively, of peroxisomal functions. In these hybrids, extinction of the
      elevated activities that characterize liver cells is observed, in parallel with
      the well-documented extinction of differentiated functions. This suggests the
      existence in fibroblasts of a negative trans-acting regulation.

PMID- 8734410
TI  - Biochemical evidence of haplodiploidy in the whitefly Bemisia tabaci.
AB  - Polymorphic esterase and acetylcholinesterase alleles in the whitefly Bemisia
      tabaci were studied using electrophoretic and colorimetric assays. The
      segregation of these alleles between parental and F1 generations provided
      unequivocal evidence of haplodiploidy in this pest species. Unmated females,
      heterozygous at a polymorphic locus, produced a 1:1 ratio of haploid males
      expressing either of the maternal alleles. Although male offspring were produced
      by both virgin and mated females, the segregation of alleles showed they were
      always haploid (hemizygous) for the marker enzymes. Females only arose from
      fertilized eggs and invariably expressed paternal and maternal alleles.

PMID- 8734411
TI  - Molecular mechanism of null expression of aldehyde dehydrogenase-1 in rat liver.
AB  - In isozyme systems in general, the pattern of tissue-dependent expression of a
      given type of isozyme is uniform in various mammalian species. In contrast, a
      major cytosolic aldehyde dehydrogenase isozyme, termed ALDH1, which is strongly
      expressed in the livers of humans and other mammals, is hardly detectable in rat
      liver. Thirteen nucleotides existing in the 5'-promoter region of human,
      marmoset, and mouse ALDH1 genes are absent in the four rat strains examined. When
      the 13 nucleotides were deleted from a chloramphenicol acetyltransferase
      expression construct, which contained the 5'-promoter region of the human ALDH1
      gene and a low-background promoterless chloramphenicol acetyltransferase
      expression vector, the expression activity was severely diminished in human
      hepatic cells. Thus, deletion of the 13 nucleotides in the promoter region of the
      gene can account for the lack of ALDH1 expression in rat liver.

PMID- 8734412
TI  - AGI, a previously unreported D. melanogaster alpha-glucosidase: partial
      purification, characterization, and cytogenetic mapping.
AB  - Inbred Drosophila melanogaster stocks were surveyed for alpha-glucosidases with
      nondenaturing gel electrophoresis using a fluorogenic substrate to stain the
      gels. The glucosidase most active under these conditions is polymorphic. We
      established that the polymorphism is genetic in origin and that the glucosidase
      was not likely to be a previously characterized enzyme. The gene encoding the
      enzyme was mapped cytogenetically to 33 A1-2- 33A8-B1, confirming that this is an
      enzyme not yet reported in D. melanogaster. The enzyme was partially purified by
      elution from nondenaturing gels, which enabled us to establish that it has
      optimal activity at pH 6 and interacts most strongly with alpha-1-4 glucosides. A
      developmental and tissue survey suggested that this enzyme could have a purely
      digestive role or be involved in carbohydrate metabolism inside the organism. We
      propose that this enzyme is involved in either starch digestion or glycogen
      metabolism.

PMID- 8734413
TI  - Genetic analysis of factors controlling high-level expression of cytochrome P450,
      CYP6D1, cytochrome b5, P450 reductase, and monooxygenase activities in LPR house
      flies, Musca domestica.
AB  - To understand better the biochemical genetics of cytochrome P450 monooxygenase
      mediated insecticide resistance, we examined the microsomal monooxygenases in
      insecticide-susceptible (aabys) and pyrethroid-resistant (LPR) house fly strains,
      as well as 15 house fly lines derived from crosses of LPR and aabys. In
      comparison to the aabys strain, LPR had higher levels of total cytochromes P450,
      cytochrome b5, P450 reductase, CYP6D1, and three P450 monooxygenase activities: 7
      ethoxycoumarin O-deethylase (ECOD), methoxyresorufin O-demethylase (MROD), and
      aromatic hydrocarbon hydroxylase (AHH). The elevated levels of cytochrome b5 were
      linked to factors on autosomes 1 and 2. This is similar to previous reports on
      monooxygenase-mediated resistance and is consistent with the idea that elevated
      cytochrome b5 levels are involved in monooxygenase-mediated resistance in the LPR
      strain. Linkage of the elevated P450 reductase is different from that of
      monooxygenase-mediated resistance. Strains having high levels of CYP6D1 (i.e.,
      like LPR) had high levels of P450 reductase, while strains having intermediate
      levels of CYP6D1 also had high levels of reductase. Therefore, there is no clear
      evidence that the elevated P450 reductase in the LPR strain is required for the
      increased monooxygenase activity. Overexpression of total cytochromes P450,
      CYP6D1 (mRNA and protein), and CYP6D1-mediated monooxygenase activities (MROD and
      AHH) in LPR microsomes was linked to a combination of factors on autosomes 1 and
      2. This demonstrates that increased expression of CYP6D1 in the LPR strain is
      both cis regulated by a factor(s) on autosome 1 and trans regulated by a
      factor(s) on autosome 2. The correlation between the overexpression of CYP6D1
      mRNA and protein suggests that CYP6D1 expression is regulated transcriptionally.
      Monooxygenase-mediated resistance in LPR is controlled by factors on autosomes 1
      and 2, which supports previous claims that CYP6D1 is responsible for
      monooxygenase-mediated resistance in the LPR strain.

PMID- 8734414
TI  - Arylsulfatase A: relationship of genotype to variant electrophoretic properties.
AB  - Previous work has shown that specific electrophoretic variants of arylsulfatase A
      occur more frequently among alcoholic patients than among psychiatric and normal
      controls. The present study sequenced the gene for two of these electrophoretic
      variants, IIIa and IIIb. Both contain an A-to-G transition corresponding to
      substitution of Asn350 by Ser, with the resulting loss of an N-glycosylation
      site. The difference in electrophoretic mobility of their gene products is due to
      a mutation in the IIIb gene resulting in the replacement of Arg496 by His.
      Evidence is presented that individuals possessing either of two other
      electrophoretic variants, Va and Vb, are heterozygous for a normal ASA allele and
      either a IIIa or IIIb allele, respectively. Thus, the relationship between the
      phenotype of the electrophoretic banding patterns, IIIa, IIIb, Va, and Vb, and
      their corresponding genotypes has been elucidated.

PMID- 8734415
TI  - Classification and differential diagnosis of clear and basal cell tumors of the
      salivary glands.
AB  - Several cell types of the salivary glands and their neoplasms may have a clear
      cytoplasm. Classification of their cytological features is made possible with
      special stainings, immunohistochemistry, and electron microscopy. Clear cell
      tumors of the salivary glands are usually formed by one distinctive cytological
      type. A new but distinct and very rare salivary gland neoplasm is the hyalinizing
      clear cell carcinoma, which should be differentiated from other clear cell
      salivary tumors. Salivary gland tumors with predominance of a basal cell
      component are basal cell adenoma, basal cell adenocarcinoma, and the solid type
      of adenoid cystic carcinoma. The differential diagnosis of clear cell and basal
      cell tumors is of great importance for the prognosis and treatment of these
      tumors.

PMID- 8734416
TI  - Maxillofacial fibro-osseous lesions: classification and differential diagnosis.
AB  - A large diversity of lesions may involve the maxillofacial bones. Some occur
      exclusively at this site. Other lesions at this location have features that are
      different from similar lesions occurring elsewhere in the skeleton. This site
      dependent morphology applies especially to fibro-osseous lesions, which will be
      discussed in this report. Fibrous dysplasia shows evenly distributed islands of
      woven bone that fuse with surrounding bone. The presence of lamellar bone and
      osteoblastic rimming does not contradict that diagnosis as they would for lesions
      occurring outside the maxillofacial bones. Ossifying fibromas are demarcated or
      encapsulated. They show a broad variation in mineralized material that may be
      woven bone as well as lamellar bone or may be present as rounded cell-poor
      particles regarded as a form of cementum. Specific subtypes are juvenile
      ossifying fibroma and psammomatoid ossifying fibroma, both of which contain
      cellular stroma exhibiting mitotic activity. Lesions known as periapical cemental
      dysplasia can be found in the tooth-bearing jaw area and are similar to ossifying
      fibroma but without demarcation. These lesions may be focal, involving one or a
      few adjacent teeth; when they are more widely distributed, they are named florid
      cemento-osseous dysplasia. Periapical cemental dysplasia should be distinguished
      from cementoblastoma, a lesion similar to osteoblastoma but connected with tooth
      apices. Ossifying fibroma may resemble well-differentiated osteosarcoma as
      ossifying fibroma may be more cellular and may have a higher number of mitoses
      than osteosarcoma.

PMID- 8734417
TI  - Benign mucosal tumors of the nose and paranasal sinuses.
AB  - The histogenesis of benign mucosal tumors of the nose and paranasal sinuses is
      reviewed in this report. In contradistinction to the view favored in the
      literature, these comprise three distinct entities. Everted and cylindric cell
      papillomas are true papillomas, lined by stratified squamous and microcyst-laden,
      columnar, and oncocytic epithelium, respectively. Inverted papillomas are polyps
      with marked, patchy squamous metaplasia in ductal and surface epithelium and
      numerous microcysts containing macrophages in those epithelia. Low-grade squamous
      carcinoma of the nose and paranasal sinuses may be difficult to distinguish from
      inverted papilloma. There are no intermediate forms from any one of the three
      types of benign mucosal tumors of the nose and paranasal sinuses to another. The
      site of origin of everted papilloma is from the nasal septum or nasal vestibular
      epithelium. Inverted and cylindric cell papillomas arise on the other hand from
      the lateral wall of the nose, ethmoid, or maxillary sinuses. Inverted papillomas
      alone among the three have a strong tendency to recur, and some cases are
      associated with carcinoma, although the development of malignancy is unusual.

PMID- 8734418
TI  - Granulomatous disorders of the oral mucosa.
AB  - A wide variety of granulomatous disorders can involve the orofacial tissues. As
      in other sites, appropriate clinicopathologic correlations are needed to reach a
      definitive diagnosis. The clinical and pathologic features of some of the more
      common oral granulomatous disorders are considered, including idiopathic
      conditions, foreign body lesions, and infectious lesions.

PMID- 8734419
TI  - Basal cell adenocarcinoma of minor salivary and seromucous glands of the head and
      neck region.
AB  - Basal cell adenocarcinoma of salivary glands is an uncommon and recently
      described entity occurring almost exclusively at the major salivary glands. This
      report provides an overview of the clinicopathologic profile of this neoplasm by
      including the personal experience on the clinical features, microscopic and
      ultrastructural characteristics, proliferation activity, and DNA tumor patterns
      of 12 lesions occurring at the minor salivary glands of the head and neck region,
      where basal cell adenocarcinoma is probably an underecognized entity, previously
      reported under different designations. Basal cell adenocarcinoma predominates at
      the seventh decade without sex preference. The tumors affecting the minor
      salivary glands occur most frequently at the oral cavity (jugal mucosa, palate)
      and the upper respiratory tract. The prevalent histologic tumor pattern is
      represented by solid neoplastic aggregates with a peripheral cell palisading
      arrangement frequently delineated by basement membrane-like material. The
      neoplastic clusters are formed by two cell populations: the small dark cell type
      (that predominates) and a large cell type. Necrosis, either of the comedo or the
      apoptotic type, is a frequent finding. Perineural growth occurs in 50% of the
      cases and vascular permeation in 25%. Immunohistochemistry identifies a dual
      differentiation with a reactivity pattern indicative of ductal epithelial and
      myoepithelial differentiation, which can be confirmed by electron microscopy. The
      differential diagnosis of the neoplasm includes its benign counterpart, the basal
      cell adenoma, solid variant of adenoid cystic carcinoma, undifferentiated
      carcinoma, and basaloid squamous carcinoma. The tumors recur more frequently than
      lesions originating in major salivary glands. Mortality is associated with the
      anatomic site of the lesion, advanced stage, residual neoplasia at surgery, and
      tumor recurrence. The importance of recognizing basal cell adenocarcinoma outside
      major salivary glands is related to the clinical behavior of the neoplasm that
      seems to be less indolent than that of tumors arising in major salivary glands.

PMID- 8734420
TI  - Myoepithelial tumors of salivary glands: a clinicopathologic,
      immunohistochemical, ultrastructural, and flow-cytometric study.
AB  - Myoepitheliomas of the salivary glands remain a controversial entity. To
      contribute to the knowledge of this entity, 16 myoepithelial tumors of the
      salivary glands were studied: 12 benign myoepitheliomas (BME) and 4 malignant
      myoepitheliomas (MME). The clinical and the histologic findings of each case were
      studied Immunohistochemistry and flow-cytometry analysis were performed from the
      paraffin-embedded material in 15 cases. An electron-microscopy study was
      performed in 8 cases. The myoepithelial tumors affected patients of both sexes
      equally. The mean age of the patients with BME was 54 years, and the mean age of
      patients with MME was 62 years. Eight cases of BME originated in the parotid
      gland and 4 cases originated in the minor salivary glands. All the MME developed
      from a benign preexistent tumor: two developed from a pleomorphic adenoma in the
      parotid gland, and the other two MME developed in the minor salivary gland from a
      BME. The myoepithelial tumors were composed of epithelioid, plasmacytoid,
      spindle, or clear cell types, and they showed a solid or a myxoid pattern of
      growth. Immunohistochemical studies revealed marked and diffuse positivity to
      cytokeratins, vimentin, and S-100 protein in all cases. Glial fibrillary acidic
      protein was positive in 8 cases (53%), and muscle-specific actin and smooth
      muscle actin were positive in only 3 cases (20%); they were all cases of BME.
      Desmin was negative in all tumors. Ultrastructural studies showed the presence of
      basal membrane, tight junctions, intermediate filaments, and microvilli as well
      as actin-like filaments lacking focal densities in all cases. But actin-like
      filaments with focal densities were not identified. Flow cytometry determined
      that all BME were diploid with a mean proliferative index of 7.73%. Two of the
      MME were diploid and the other two MME were aneuploid. The mean proliferative
      index of MME was 11.93%. In conclusion, BME and MME originated in major and minor
      salivary glands can display different histologic patterns and cellular features.
      Some immunohistochemical and ultrastructural characteristics have been found in
      all these neoplasms, which supports the idea that myoepitheliomas are composed by
      neoplastic modified myoepithelial cells, not fully differentiated. These
      techniques can be useful for the diagnosis of these tumors.

PMID- 8734421
TI  - Cloning of cDNAs from a mammalian expression library by a direct selection
      amplification method.
AB  - A sensitive method was devised for cloning cDNAs from a mammalian expression
      library based on single-cell detection and selection of transfected cells. The
      method is applicable for cloning cell-surface or cytoplasmic proteins for which a
      detection assay, such as immunofluorescence or immunohistochemical reactivity,
      exists. The widely used eukaryotic expression vector cdm8 is utilized, and the
      method is demonstrated using the gene for C-CAM, a liver glycoprotein adhesion
      molecule. After transfection, cells are plated out on a collagen gel substrate to
      allow retrieval of selected cells. Simultaneous fixation and permeabilization
      with acetone permits immunological and histochemical detection of cell-surface
      and cytoplasmic proteins without loss of plasmid vector. Inserts of interest are
      recovered by PCR with vector primers.

PMID- 8734422
TI  - Transgenic grain legumes obtained by in planta electroporation-mediated gene
      transfer.
AB  - Electroporation-mediated gene transfer into intact plant tissues was demonstrated
      in pea, cowpea, lentil, and soybean plants. Transient expression of a chimeric
      gus reporter gene was used to monitor the uptake and expression of the introduced
      DNA in electroporated nodal axillary buds in vivo. The branches that grew out of
      the nodal meristems were chimeric and expressed the introduced gene up to 20 d
      after electroporation. Transgenic R1 pea, lentil, and cowpea plants were
      recovered from seeds originating on these chimeric branches as shown by Southern
      blot hybridization and GUS expression. Transgenic R2 soybean and lentil plants
      were also obtained. Segregation ratios in these populations showed a strong bias
      against transgene presence or expression.

PMID- 8734423
TI  - Isolation and characterization of the restriction endonuclease PpeI from
      Phormidium persicinum.
AB  - PpeI is a type II restriction endonuclease isolated from cyanobacterial strain
      Phormidium persicinum. The endonuclease PpeI, an isoschizomer of ApaI, recognizes
      the hexanucleotide sequence (5'-GGGCC/C-3') and cleaves, after the second C,
      producing four nucleotide 3'-cohesive ends.

PMID- 8734424
TI  - The analysis of fluorophore-labeled carbohydrates by polyacrylamide gel
      electrophoresis.
AB  - The glycans of glycoconjugates mediate numerous important biological processes.
      Their separation and structural determination present considerable difficulties
      because of the small quantities that are available from biological sources and
      the inherent difficulty of analyzing the wide variety of complex structures that
      exist. A method for the analysis of reducing saccharides by PAGE that uses
      specific fluorophore labeling and is simple, rapid, sensitive, and readily
      available to biological researchers, has been developed. This method is known
      acronimically either as PAGEFS (PAGE of Fluorophore-labeled Saccharides) or in
      one commercial format as FACE (Fluorophore-Assisted Carbohydrate
      Electrophoresis). In the PAGEFS method, saccharides having an aldehydic reducing
      end group are labeled quantitatively with a fluorophore and then separated with
      high resolution by PAGE. Two fluorophores, 8-aminonaphthalene-1,3,6-trisulfonic
      acid (ANTS) and 2-aminoacridone (AMAC), have been used to enable the separation
      of a variety of saccharide positional isomers, anomers, and epimers. Subpicomolar
      quantities of individual saccharides can be detected using a sensitive imaging
      system. Mixtures of oligosaccharides obtained by enzymatic cleavage from
      glycoproteins can be labeled and electrophoresed to yield an oligosaccharide
      profile of each protein. AMAC can be used to distinguish unequivocally between
      acidic and neutral oligosaccharides. Methods of obtaining saccharide sequence
      information from purified oligosaccharides have been developed using enzymatic
      degradation. Other applications and the potential of the system are described.

PMID- 8734425
TI  - Acyclic nucleosides as antiviral compounds.
AB  - Acyclovir is an effective drug for the treatment of HSV and VZV infections, which
      after phosphorylation to the triphosphate, inhibits viral DNA polymerase.
      Acyclovir has low oral bioavailability, therefore prodrugs have been developed,
      and the L-valyl ester, valaciclovir, recently has been licensed for the treatment
      of shingles. Ganciclovir is used against CMV, and famciclovir, a lipophilic
      prodrug of penciclovir, is marketed for shingles. The acyclic nucleoside
      phosphonates are active against thymidine kinase-resistant viral strains.
      Promising analogs are PMEA (in clinical trial for the treatment of AIDS) and (S)
      HPMPC (good in vivo activity against HSV, VZV, CMV, and EBV). Oligonucleotides
      incorporating acyclic nucleosides at the 3'-and 5'-ends, or constituted of amino
      acyclic nucleosides, are resistant to cleavage by nucleases and may be useful in
      antisense and/or antigene therapy. HEPT is active against HIV-1: It binds in a
      hydrophic pocket on reverse transcriptase, rather than in the polymerase active
      site. Some acyclic nucleosides are potent inhibitors of purine and pyrimidine
      nucleoside phosphorylase. These compounds may have a therapeutic niche in
      combination therapy with antiviral and anticancer nucleosides, and in the
      treatment of diseases involving the T-cell.

PMID- 8734427
TI  - Sequencing of double-stranded PCR products.
AB  - Very often the experimental step following PCR is sequencing of the amplified
      fragment. Two protocols that allow direct sequencing of a double-stranded PCR
      product are described. The first involves removal of one strand of the PCR
      product using an M13 single-stranded DNA clone, allowing the second strand to be
      sequenced. The second protocol involves Maxam-Gilbert chemical sequencing after
      PCR amplification with one labeled primer. The advantages and disadvantages of
      the two protocols are compared, but both yield DNA sequence without cloning of
      the PCR product.

PMID- 8734426
TI  - Retroviral vectors. From laboratory tools to molecular medicine.
AB  - The majority of clinical trials for gene therapy currently employ retroviral
      mediated gene delivery. This is because the life cycle of the retrovirus is well
      understood and can be effectively manipulated to generate vectors that can be
      efficiently and safely packaged. Here, we review the molecular technology behind
      the generation of recombinant retroviral vectors. We also highlight the problems
      associated with the use of these viruses as gene therapy vehicles and discuss
      future developments that will be necessary to maintain retroviral vectors at the
      forefront of gene transfer technology.

PMID- 8734428
TI  - High-resolution glycoprotein analysis using capillary electrophoresis.
AB  - The high-resolution separation achievable with capillary electrophoresis has been
      applied successfully to the analysis of glycoproteins. Inherent in the
      implementation of this technology for glycoprotein analysis is the use of
      specific buffer additives. Bifunctional cationic reagents, such as simple alkyl
      chains bearing terminal amino or quaternary ammonium groups, have been
      particularly useful for the analysis of ovalbumin, an excellent model
      glycoprotein. Although dynamic coating of the capillary wall and the subsequent
      decrease in protein-wall interactions in known to be key in the effectiveness of
      these additives, much remains to be learned regarding the mechanism through which
      they function.

PMID- 8734429
TI  - Identification of glycoproteins on nitrocellulose membranes and gels.
AB  - In this article we describe a procedure for the detection of glycoproteins on
      gels employing the periodic acid-Schiff's reagent. In addition, a number of
      staining protocols and direct binding ELISA, employing antibodies and lectins,
      are described for the identification and quantitation of glycoproteins after
      their immobilization by dot, slot, or Western blotting onto nitrocellulose
      membranes. We document, in detail, the conditions (i.e., the effect of solvent
      and detergents) for the immobilization of one specific family of O-linked
      glycoproteins, namely mucins. However, taking into account our suggestions, these
      procedures should be applicable to other types of glycoprotein.

PMID- 8734430
TI  - Rapid removal of unincorporated label and proteins from DNA sequencing reactions.
AB  - This article presents a simple and rapid method for removal of unincorporated
      label and proteins from DNA sequencing reactions by using Wizard purification
      resin. This method can be successfully applied for preparation of end-labeled
      oligonucleotides free of unincorporated label, which is important in experiments
      (including DNA sequencing) when the level of background should be as low as
      possible. Also, this method is effective in removal of proteins from DNA
      sequencing reactions.

PMID- 8734431
TI  - Expression of mRNA for a sodium channel in subfamily 2 in spinal sensory neurons.
AB  - RNA blot analysis and non-isotopic in situ hybridization cytochemistry were used
      to study the expression of the mRNA for the glial sodium channel NaG, belonging
      to Na+ channel subfamily 2, in rat dorsal root ganglia (DRG). mRNA hybridizing at
      high stringency with an antisense riboprobe against the NaG sequence was observed
      in both Schwann cells and spinal sensory neurons in situ within DRG, but was
      expressed at higher levels in the latter. In contrast, hybridization was not
      detectable in neurons within hippocampus, cerebellum and spinal cord. The
      expression of the mRNA hybridizing with the NaG probe appears to be
      developmentally regulated in both Schwann cells and DRG neurons, with levels
      increasing as development proceeds. Thus, in addition to the mRNAs for types I
      and II/IIA alpha-subunits and beta 1-subunit in DRG neurons and types II/IIA and
      III alpha-subunits beta 1-subunit in Schwann cells, the mRNA for an additional
      sodium channel belonging to subfamily 2 is expressed in these cells in situ.

PMID- 8734432
TI  - Expression of a unique globo-series glycolipid in cultured rat dorsal root
      ganglion neurons: relationship with neuronal development.
AB  - Previous studied from the laboratory demonstrated the presence of a UDP
      galactose:Gb3Cer alpha 1-3galactosyltansferase activity responsible for the
      synthesis of a unique glycosphingolipid (GSL), Gal alpha 1-3Gb3Cer, in cultured
      PC12 pheochromocytoma cells (21). In this investigation, we examined the presence
      of this enzyme activity in isolated rat embryonic dorsal root ganglion neurons
      (DRGN), which, like pheochromocytoma cells, originate from the neural crest
      cells. DRGN exhibited the alpha-galactosyltransferase activity and the activity
      was comparable to that of the PC12 cells while several other rat tissues, with
      the exception of kidney, showed minimal activity. In order to define the spatial
      and temporal expression of Gal alpha 1-3Gb3Cer in DRGN, we examined the
      expression of Gal alpha 1-3Gb3Cer in cultured DRGN derived from embryonic day 16
      rat embryos. Using a polyclonal antibody raised against Gal alpha 1-3Gb3Cer, we
      examined the localization of this glycolipid in DRGN cells after 5, 8, 12, and 15
      days in culture. Immunostaining was restricted to the neurons while Schwann cells
      were negative. At day 5, the immunostaining was weak and confined to the cell
      body of the DRGN, though neurites were present at this stage. The period between
      days 5 and 15 represented a period of rapid neuritic growth and continued
      enlargement of the cell bodies. Immunoreactivity in the cell bodies increased
      dramatically by day 8. By day 12, immunoreactivity was present in neurites, and
      by day 15, was strong in both cells bodies and neurites. The expression of Gal
      alpha 1-3Gb3Cer in vivo was confirmed by immunostaining of frozen sections of
      dorsal root ganglia. Our present studies which demonstrate neuron-specific
      expression of Gal alpha 1-3Gb3Cer during neurotigenesis combined with previous
      observations for its expression in PC12 cells, strongly implicates this GSL in
      neuronal development.

PMID- 8734433
TI  - Expression of carbonic anhydrase II mRNA and protein in oligodendrocytes during
      toxic demyelination in the young adult mouse.
AB  - The aim of this study was to identify events that might take place in
      oligodendrocytes early in the process of demyelination, i.e., before the
      occurrence of massive loss of myelin. It was considered important to focus on
      demyelination and remyelination in young adults, in whose brains there would be
      relatively few juvenile glial precursor cells. CAII mRNA and protein were used to
      monitor changes in oligodendrocytes during cuprizone intoxication in the mice.
      After four or eight weeks of cuprizone feeding CAII message became less plentiful
      in oligodendrocyte processes. Two days after removal of cuprizone CAII message
      had appeared in those cell processes. Four or eight weeks after beginning
      cuprizone feeding CAII protein had decreased approximately 25% in forebrain
      homogenates. The loss of CAII protein was reversible after four weeks on
      cuprizone, but not after eight weeks. After four weeks of cuprizone feeding the
      numbers of CAII mRNA-positive oligodendrocytes had decreased by approximately
      50%, and after eight weeks, by approximately 80%. By 12 weeks, however, the
      number of oligodendrocytes expressing CAII mRNA had spontaneously returned to
      normal levels. Before eight weeks of cuprizone feeding, loss of myelinated tracts
      in the corpus striatum was reversible. Demyelination appeared to become
      irreversible after nine weeks of intoxication, although expression of CAII mRNA
      remained reversible. The results suggest that in the brain of the young adult,
      oligodendrocytes expressing message for CAII can be generated spontaneously
      shortly before demyelination becomes irreversible, and can survive and continue
      to express CAII mRNA but not CAII protein.

PMID- 8734434
TI  - Antisense oligonucleotide to the 70-kDa heat shock cognate protein inhibits
      synthesis of myelin basic protein.
AB  - Transfection of rat oligodendrocytes with an oligonucleotide sequence
      complementary to the mRNA encoding the initial ten amino acids of the rat 70-kDa
      heat shock cognate protein (HSC70) resulted in a rapid (within 24 h) and
      significant reduction in HSC70 synthesis (69% of control cells transfected with
      sense oligonucleotide). A further decrease to approximately 44% of controls was
      detected after 2 days. At that time, HSC70 protein content fell to approximately
      49% of controls, and a significant reduction in the synthesis of myelin basic
      protein (MBP) was first detected (66% of controls). After 5 days, HSC70 synthesis
      returned to control levels. As HSC70 protein content recovered, so did the
      synthesis of MBP. Throughout the 5-day experimental period, only minor changes
      were detected in cell morphology, overall pattern of protein synthesis and the
      synthesis and content of proteolipid protein (PLP) and the pi isoenzyme of
      glutathione-S-transferase (pi). These data show that when HSC70 protein content
      is sufficiently reduced by antisense oligonucleotide, synthesis of MBP (but not
      PLP or pi) is correspondingly down-regulated, and provide evidence consistent
      with the role of HSC70 as a chaperone for MBP.

PMID- 8734435
TI  - Proteolipid/DM-20 proteins bearing the paralytic tremor mutation in peripheral
      nerves and transfected Cos-7 cells.
AB  - Paralytic tremor (Plp-pt) is a missense mutation of the myelin proteolipid gene
      (Plp) in rabbits. The myelin yield in the Plp-pt brain is reduced and the protein
      and lipid composition of central nervous system (CNS) myelin is abnormal. We
      studied the intracellular transport of the normal and Plp-pt mutant PLP and DM-20
      in transiently transfected Cos-7 cells. While the mutant PLP accumulates in the
      rough endoplasmic reticulum and does not reach the plasma membrane, the spliced
      isoform of PLP, mutant DM-20, is normally transported to the cell surface and
      integrated into the membrane. Analysis of rabbit sciatic nerves revealed that
      concentration of peripheral nervous system (PNS) myelin proteins is normal in Plp
      pt myelin. In the PNS like in the CNS, the level of Plp gene products is
      subnormal. But this does not affect myelination in the PNS where PLP, present in
      low concentration, is not a structural component of compact myelin. The normal
      level of Plp gene expression in Schwann cells is low and these results suggest
      that, in the Plp-pt PNS, Schwann cell function is not affected by the deficiency
      in PLP and/or the impairment of intracellular PLP transport.

PMID- 8734436
TI  - Orientation of myelin proteolipid protein in the oligodendrocyte cell membrane.
AB  - The orientation of proteins within a cell membrane can often be difficult to
      determine. A number of models have been proposed for the orientation of the
      myelin protein, proteolipid protein (PLP), each of which includes exposed domains
      on the intracellular and extracellular membrane faces. Immunolabeling experiments
      have localized the C-terminus and the region spanning amino acids 103-116 to the
      cytoplasmic face of the membrane, but no well characterized antibodies have been
      available that label extracellular PLP domains. In this report, we describe the
      generation and characterization of mouse monoclonal antibodies (mAb) against
      putative extramembrane domains. Three of the mAb, specific for PLP peptides 40
      59, 178-191, or 215-232, immunostain live oligodendrocytes, indicating that these
      regions of the molecule are exposed on the external surface of the cell. In
      addition, we have used these mAb to study the time-course of incorporation of PLP
      into the oligodendrocyte membrane. These studies increase our knowledge of the
      orientation of PLP in the lipid bilayer and are relevant for understanding myelin
      function.

PMID- 8734437
TI  - Role of calpain in spinal cord injury: increased calpain immunoreactivity in rat
      spinal cord after impact trauma.
AB  - Impact spinal cord injury (20 g-cm) was induced in rat by weight drop. The
      immunoreactivity of mcalpain was examined in the lesion and adjacent areas of the
      cord following trauma. Increased calpain immunoreactivity was evident in the
      lesion compared to control and the immunostaining intensity progressively
      increased after injury. The calpain immunoreactivity was also increased increased
      in tissue adjacent to the lesion. mCalpain immunoreactivity was significantly
      stronger in glial and endothelial cells, motor neurons and nerve fibers in the
      lesion. The calpain immunoreactivity also increased in astrocytes and microglial
      cells in the adjacent areas. Proliferation of microglia and astrocytes identified
      by GSA histochemical staining and GFAP immunostaining, respectively, was seen at
      one and three days after injury. Many motor neurons in the ventral horn showed
      increased calpain immunoreactivity and were shrunken in the lesion. These studies
      indicate a pivotal role for calpain and the involvement of glial cells in the
      tissue destruction in spinal cord injury.

PMID- 8734438
TI  - The 66-kDa neurofilament protein (NF-66): sequence analysis and evolution.
AB  - A 2.5 kb cDNA clone encoding the mouse 66 kd neurofilament protein (NF-66) was
      isolated and sequenced. The deduced protein sequence contains 501 amino acid
      residues. Comparison of the mouse, rat and human NF-66 indicated > 90% homology
      in protein sequence and 85% homology in coding nucleotide sequence. A high degree
      of homology was observed between NF-66 and other intermediate filament proteins
      especially in the alpha-helical domain. Zooblot analyses suggested that the
      putative ancestral gene for vimentin and NF-66 was detectable in the avian. By
      comparison, the ancestral sequence for GFAP appeared after that for vimentin.

PMID- 8734439
TI  - Characterization of guanylyl cyclase in purified myelin.
AB  - This study was undertaken to characterize the enzymatic properties of the
      particulate guanylyl cyclase previously shown to be present at a high level of
      activity in purified rat brain myelin. Significant activation was achieved by
      both Lubrol-PX and Triton X-100, the latter being somewhat more effective. A pH
      optimum of 7.8 was observed, compared to 7.4 for microsomes. Employing 1.2 mM GTP
      with 1% Triton X-100, linearity of response was observed up to 60 min and
      approximately 1.2 mg of myelin protein. Kinetic analysis revealed Km values of
      0.258mM and 0.486mM for myelin and microsomes, respectively, similar values being
      obtained by Lineweaver-Burke analysis or Direct Linear Plot. Vmax values were 20
      and 266 pmol/mg protein/min for myelin and microsomes, respectively. Washing of
      the myelin with 0.5 M NaCl or 0.1% Na taurocholate did not remove a significant
      amount of guanylyl cyclase activity, indicating the enzyme to be intrinsic to the
      myelin sheath.

PMID- 8734440
TI  - Origin of cholesterol in myelin.
AB  - We review some of the older literature concerning metabolic turnover of
      cholesterol in the nervous system. The overall picture is that incorporation of
      radioactive precursors into brain cholesterol is roughly proportional to the rate
      of myelination and that, once incorporated, radioactive cholesterol is relatively
      stable metabolically. We outline a strategy for demonstrating the source (local
      synthesis or uptake from circulation) of cholesterol in brain. The experimental
      design involves determining the rate of accumulation of cholesterol; this is
      calculated as the increasing amounts of sterol in brain at successive time
      intervals during development. The rate of appearance of newly synthesized
      cholesterol is determined from incorporation of radioactivity from 3H20 (injected
      i.p. several hours prior to sacrifice) into cholesterol. The radioactivity
      associated with the sterol fractions and the specific activity of body water
      determined from the serum can be used to calculate the absolute amount of sterol
      newly synthesized during the time when 3H20 was present. The results obtained
      demonstrated that all of the bulk cholesterol accumulating in brain can be
      accounted for by newly synthesized cholesterol. None of the radioactive
      cholesterol came from the circulation, since cholesterol feeding suppressed
      cholesterol biosynthesis in the liver and specific radioactivity of circulating
      cholesterol was negligible. Thus, almost all cholesterol accumulating in brain
      during development is locally synthesized.

PMID- 8734441
TI  - Release of intracellular calcium stores leads to retraction of membrane sheets
      and cell death in mature mouse oligodendrocytes.
AB  - The ability of mature oligodendrocytes (OLs) to recover from insult is important
      in repair of damage following demyelination. Since regulation of Ca2+ levels
      within cells plays a critical role in function and survival, this study
      investigates the effects of changes in cytoplasmic Ca2+ on the viability of
      cultured mouse OLs and their ability to maintain membrane sheets. Mature OLs in
      culture respond rapidly to the calcium ionophore A23187 and promptly return to
      resting Ca2+ levels when the ionophore is removed. Longer exposure to 0.1-1.0
      microM A23187 leads to microtubule disruption, membrane sheet retraction and
      eventual cell death; nuclear lysis occurs in many of the OLs, as reported by
      Scolding, et al. (1) for rat OLs. In our cultures, mature OLs were more
      susceptible to nuclear lysis than were immature OLs or astroglia. Release of
      intracellular Ca2+ stores with thapsigargin at 5-10 microM also leads to
      retraction of membrane sheets. Following 6 hours of continuous exposure to
      thapsigargin, the effects on membrane sheets are reversed over the next 12 hours.
      After 18 hours of continuous exposure to thapsigargin, only occasional nuclear
      lysis is observed, but a number of the mature OLs show signs of DNA
      fragmentation, indicating that apoptotic death is occurring. Our results suggest
      that mature OLs cannot survive a prolonged influx of extracellular calcium as
      readily as immature OLs and astroglia, but have mechanism to withstand similar
      increases in cytoplasmic Ca2+ following sustained release of intracellular
      stores.

PMID- 8734442
TI  - Receptor-mediated phagocytosis of myelin by macrophages and microglia: effect of
      opsonization and receptor blocking agents.
AB  - Myelin is phagocytosed by microglia (MG) and to a somewhat lesser extent by
      peritoneal macrophages (M phi) in a dose- and time-dependent manner. In serum
      free medium opsonization of rat myelin significantly enhances binding and
      ingestion, more by rat macrophages than by microglia. Furthermore the requirement
      for opsonization is not restricted to anti-myelin antibodies as the difference in
      the rate of myelin uptake by macrophages is largely eliminated when they are
      cultured in 10% fetal calf serum. Binding and ingestion of both myelin and
      opsonized myelin are inhibited to the same dose-dependent extent by zymosan,
      oxidized LDL, peroxidase-antiperoxidase (PAP), opsonized erythrocytes and the
      anti-CR3 antibody OX42 implicating lectin, scavenger, Fc and complement receptors
      in the phagocytosis of myelin. Thus while the differential uptake of myelin and
      opsonized myelin by macrophages would indicate a central role for the Fc
      receptor, binding inhibition studies implicate a range of membrane receptors
      which would obviate the need for antigen-antibody complexing to stimulate
      phagocytosis. Uptake of both myelin preparations by macrophages or microglia is
      stimulated by interferon-gamma and inhibited by TGF-beta, and the process of
      ingestion results in increased nitric oxide release and decreased superoxide
      production, the effect being more pronounced when myelin is opsonized.

PMID- 8734443
TI  - Effects of exogenous triiodothyronine on fast axonal transport during tadpole
      metamorphosis.
AB  - Bullfrog tadpoles at metamorphic stages V, X and XVIII were immersed in 25 nM
      triiodothyronine (T3) to assess whether the 4-5 fold increase in fast axonal
      transport (FAxT) previously observed during this span of spontaneous
      metamorphosis (1) could be mimicked by precocious application of thyroid hormone.
      The trend initially observed was for T3 to stimulated [35S]methionine
      incorporation into lumbar DRG and inhibit incorporation in tail DRG. Both
      effects, however, appeared to be exerted primarily on satellite cells rather than
      neurons since most of the T3-induced changes in DRG were of a similar magnitude
      to those in the respective nerve trunks. Findings consistent with this
      observation resulted from use of the retrogradely transported lectin, ricin120,
      to determine the proportion of DRG incorporation occurring in neurons. When
      incorporation of [35S]methionine in lumbar DRG neurons was examined, T3 had no
      stimulatory effect at any of the metamorphic stages examined. When FAxT was
      assessed as [35S]protein accumulating proximal to a nerve trunk ligature, and
      expressed as a percentage of newly-synthesized protein in lumbar DRG neurons, no
      stimulatory effect of T3 was detected. The question remains whether the changes
      in FAxT in peripheral neurons observed during spontaneous metamorphosis may be
      induced by circulating hormones other than T3 or are secondary to changes in the
      target tissues.

PMID- 8734445
TI  - Monoclonal antibodies to proteins of the myelin-like sheath of earthworm giant
      axons show cross-reactivity to crayfish CNS glia: an immunogold electron
      microscopy study.
AB  - Monoclonal antibodies were generated to the proteins in myelin-like membranes
      isolated from the nerve cords of the earthworm, Lumbricus terrestris. One of
      these showing cross-reactivity to 30-32 and 40 kDa proteins was shown by
      immunofluorescence microscopy and immunogold electron microscopy to be bound
      primarily to glial cell process and their membranes and the myelin-like layers.
      This antibody cross-reacted with proteins of 60-65, 42, and 40 kDa in crayfish
      (Procambarus clarki) nerve cord homogenates. Localization by immunoelectron
      microscopy showed the antibody to be bound exclusively to the membranes of the
      glial processes ensheathing the axons in the crayfish nerve cord. Thus, the
      proteins in earthworm and crayfish glial cell membranes have some epitopes in
      common. We suggest that this may represent an evolutionary conservation of these
      proteins.

PMID- 8734444
TI  - Do oligodendrocytes divide?
AB  - Remyelination occurs in the adult central nervous system following a wide variety
      of experimental and naturally occurring demyelinating conditions, including
      multiple sclerosis. Remyelination is preceded by the appearance of new
      oligodendrocytes. These new cells may be generated from glial precursor cells, or
      from pre-existing differentiated oligodendrocytes that re-enter the cell cycle,
      which may first dedifferentiate, or both processes may occur. The evidence for
      the source of new oligodendrocytes following toxic or immune-mediated lesions is
      reviewed. Good evidence exists that fully differentiated oligodendrocytes can
      incorporate [3H]thymidine but this may be a rare event. Most of the evidence
      points towards glial precursor cells as the source of new oligodendrocytes in the
      adult, but definitive experiments have not yet been done. Research strategies,
      using our current knowledge and techniques, are outlined for solving this
      problem.

PMID- 8734446
TI  - Inflammation in EAE: role of chemokine/cytokine expression by resident and
      infiltrating cells.
AB  - Experimental allergic encephalomyelitis (EAE) is an inflammatory demyelinating
      disease of the central nervous system (CNS) which has many clinical and
      pathological features in common with multiple sclerosis (MS). Comparison of the
      histopathology of EAE and MS reveals a close similarity suggesting that these two
      diseases share common pathogenetic mechanisms. Immunologic processes are widely
      accepted to contribute to the initiation and continuation of the diseases and
      recent studies have indicated that microglia, astrocytes and the infiltrating
      immune cells have separate roles in the pathogenesis of the MS lesion. The role
      of cytokines as important regulatory elements in these immune processes has been
      well established in EAE and the presence of cytokines in cells at the edge of MS
      lesions has also been observed. However, the role of chemokines in the initial
      inflammatory process as well as in the unique demyelinating event associated with
      MS and EAE has only recently been examined. A few studies have detected the
      transient presence of selected chemokines at the earliest sign of leukocyte
      infiltration of CNS tissue and have suggested astrocytes as their cellular
      source. Based on these studies, chemokines have been postulated as a promising
      target for future therapy of CNS inflammation. This review summarized the events
      that occur during the inflammatory process in EAE and discusses the roles of
      cytokine and chemokine expression by the resident and infiltrating cells
      participating in the process.

PMID- 8734448
TI  - Gonadotrophin receptors.
AB  - Precocious puberty may be gonadotrophin-dependent, due to premature activation of
      the hypothalamic GnRH pulse generator, or gonadotrophin-independent wherein serum
      LH and FSH levels are undetectable despite near-adult levels of gonadal
      steroidogenesis. In one form of gonadotrophin-independent familial male
      precocious puberty (FMPP) activating mutations of the LH receptor cause
      constitutive activation of the cAMP signal transduction cascade in Leydig cells
      with attendant testosterone biosynthesis. The LH receptor is a member of the
      seven transmembrane group of receptors coupled to signal transduction through GTP
      binding intermediate proteins. In FMPP the initial mutations were described in
      the sixth membrane spanning domain close to the third intracellular loop which is
      known to be important for coupling to the subunit of the stimulatory GTP binding
      protein Gs. Subsequently, activating mutations at several other sites in the LH
      receptor have been described. Activating mutations in the second step of the
      signalling cascade, the GTP binding protein Gs, have been described in sporadic
      somatotrophinomas in the pituitary and solitary thyroid adenomas. The McCune
      Albright syndrome may also be rarely associated with pituitary and thyroid
      adenomas, in addition to the more common polyostotic fibrosus dysplasia and
      gonadotrophin-independent precocious puberty. Thus, in the luteinized ovarian
      tissue of patients with this condition activating mutations in Gs alpha subunit
      have been described at codon 201. These mutations are somatic, not germ line, and
      only one allele needs to be affected as they are dominant. In an uncommon form of
      male pseudohermaphroditism associated with hypergonadotrophic hypogonadism and
      Leydig cell hypoplasia, inactivating mutations of the LH receptor are described.
      These, too, are in the sixth transmembrane domain and both alleles must be mutant
      as the condition is autosomal recessive. These 'experiments of nature' have
      provided invaluable insights into the structure-function relations of the LH
      receptor, and the mutations described have been recreated and studied in vitro,
      where the predicted activation or failure to stimulate steroidogenesis confirm
      their pathogenic nature. As yet no such activating or inhibiting mutations in the
      FSH receptor gene have been described, but it is likely these will be forthcoming
      in future.

PMID- 8734447
TI  - Phosphorylation of myelin protein: recent advances.
AB  - Since it was first described 25 years ago, phosphorylation has come to be
      recognized as a widespread and dynamic post-translation modification of myelin
      proteins. In this review, the phosphorylation characteristics of myelin basic
      protein, protein zero (P0), myelin-associated glycoprotein and 2'3' cyclic
      nucleotide 3'-phosphodiesterase are summarized. Emphasis is placed on recent
      advances in our knowledge concerning the protein kinases involved and the sites
      of phosphorylation in the amino acid sequences, where known. The possible roles
      of myelin protein phosphorylation in modulating myelin structure, the process of
      myelin assembly and mediation of signal transduction events are discussed.

PMID- 8734449
TI  - The TSH receptor and thyroid diseases.
AB  - Recent advances in the understanding of the molecular biology of the TSH receptor
      have had a considerable impact on several aspects of thyroidology. The
      identification and functional characterization of mutations in the TSH receptor
      gene which constitutively activate the TSH receptor in the absence of its ligand
      provide an explanation for the molecular mechanism which is most likely
      responsible for the majority of the hyperfunctioning thyroid adenomas. Moreover,
      these constitutively activating mutations also cause a new form of familial
      hyperthyroidism: non-autoimmune autosomal dominant hyperthyroidism and also
      sporadic cases of congenital non-autoimmune hyperthyroidism. TSH receptor
      mutations which cause a reduced sensitivity to TSH have been identified as the
      cause of non-autoimmune congenital hypothyroidism. TSH receptor mRNA variants
      have been found in thyroid associated ophthalmopathy. If protein expression for
      these variants can be demonstrated, this finding could advance our understanding
      of thyroid associated ophthalmopathy. The ability to produce large quantities of
      TSH receptor protein in bacteria has led to the generation of more sophisticated
      assays for TSH receptor antibodies and enabled the generation of an animal model
      for thyroid autoimmunity.

PMID- 8734450
TI  - The ACTH receptor.
AB  - The ACTH-R is a receptor that has a prominent role in mammalian physiology, but
      which has been notoriously difficulty to study. The cloning of the gene encoding
      this receptor in 1992 should permit significant advances in the understanding of
      the physiology, pharmacology and pathophysiology of ACTH. Areas of particular
      interest that should be clarified in the next few years are the control of the
      tissue specific expression of the gene, and an understanding of the molecular
      determinants of the ligand-receptor interaction. This latter area raises the
      prospect of clinically useful, orally active ACTH agonists and antagonists.

PMID- 8734451
TI  - Insulin-like growth factor receptors and binding proteins.
AB  - The insulin-like growth factor receptors are integral membrane proteins and
      demonstrate separate, but important effects on the regulation of cellular
      processes. The IGF-I receptor signals multiple cascades via its inherent tyrosine
      kinase activity. The IGF-II/M-6-P receptor on the other hand is primarily
      involved in targeting of enzymes to various subcellular compartments. In
      contrast, the insulin-like binding proteins are secreted by the cells and
      accumulate in the extracellular matrix or on the external surface of the cell.
      They are also involved in regulating cellular processes more indirectly. They
      modulate the interactions of the IGFs with their receptors, and in addition, may
      have some IGF-independent effects probably by direct interaction with integrin
      and other cell membrane receptor proteins. The recent studies, as outlined in
      this review, strongly suggest an important, if not essential role for the IGF
      system in normal physiology and disease states. The challenge now is to define
      the mechanisms involved in these effects. More studies are required to fully
      understand the post-receptor mechanism involved in IGF-I receptor signal
      transduction and the mechanisms whereby the IGFBPs exert their interesting
      effects. Understanding these mechanisms will enable investigators to create new
      therapeutic modalities for diseases that are affected by the IGF system.

PMID- 8734452
TI  - Vasopressin and oxytocin receptors.
AB  - The oxytocin and the vasopressin V1a, V1b and V2 receptors have recently been
      cloned and shown to form a sub-family within the large superfamily of G-protein
      linked receptors. Renal V2 receptors mediate vasopressin-induced water
      reabsorption via induction of intracellular cAMP production in collecting duct
      cells. Most remaining actions of vasopressin on blood vessel constriction, liver
      glycogenolysis, platelet adhesion, adrenal angiotensin II secretion and certain
      brain functions are mediated via v1a-type receptors that are coupled to a Gq/11
      protein. V1 receptor activation leads to stimulation of phospholipases C, D and
      A2 and an increase in intracellular calcium. Vasopressin stimulates pituitary
      corticotrophin release via a third vasopressin receptor type (V1b) which is
      present on corticotrophs. Oxytocin induces myometrial contraction, endometrial
      prostaglandin F2 alpha production, mammary gland milk ejection, renal natriuresis
      and specific sexual, affiliative and maternal behaviours via oxytocin receptors
      which are also coupled to a Gq/11 protein. Although only one oxytocin receptor
      type has been cloned so far, recent binding studies indicate that uterine
      endometrial oxytocin receptors may constitute a distinct receptor subtype. In
      contrast to most other membrane receptors, the expression of oxytocin receptors
      undergoes very rapid and physiologically relevant up-and-down-regulation. A > 100
      fold up-regulation of uterine oxytocin receptors occurs during gestation and may
      represent the trigger for parturition. Indeed, oxytocin receptor antagonists are
      able to counteract preterm labour and may soon be available for clinical use. The
      presence of oxytocin receptors on breast cancer cells and the growth-inhibitory
      effects of OT suggest a potential use of oxytocin analogues for breast cancer
      treatment. Whereas no mutations of the oxytocin or V1a or V1b receptors have been
      found, over 60 different genetic mutations of the (renal) V2 receptor have been
      described which represent the cause for congenital nephrogenic diabetes
      insipidus.

PMID- 8734453
TI  - Mutant insulin receptors in syndromes of insulin resistance.
AB  - To date, mutations of the insulin receptor remain the only well-established
      causes of severe insulin resistance. There is a broad correlation between the
      extent of impairment of signal transduction seen when the mutant receptors are
      expressed in vitro with the severity of the clinical phenotype. Thus
      leprechaunism, Rabson-Mendenhall syndrome and Type A insulin resistance appear to
      represent points on a continuum of severity of receptor dysfunction, rather than
      completely distinct syndromes. In other syndromes of insulin resistance, insulin
      receptor abnormalities remain the exception. However, functional studies of
      expressed naturally occurring insulin receptor mutations have acted as
      experiments of nature and greatly aided attempts to dissect the structure
      function relationships of the receptor. The next few years will no doubt begin to
      reveal the contributions made by defects in the post-receptor signalling cascade
      to the syndromes of insulin resistance in man.

PMID- 8734454
TI  - Serpentine receptors for parathyroid hormone, calcitonin and extracellular
      calcium ions.
AB  - The cloning of the receptors for PTH, CT and extracellular calcium ions
      represents a significant advance in the elucidation of the mechanisms through
      which extracellular calcium ions are regulated. All are members of the
      superfamily of GPCR, and the inclusion of the Ca2+o-sensing receptor in this
      superfamily documents that extracellular calcium ions can serve as an
      extracellular first messenger, in addition to subserving their better known role
      as a key intracellular second messenger. Furthermore, it has proved possible to
      identify several human diseases that result from inactivating or activating
      mutations in the PTH or Ca2+o-sensing receptor. Finally, the availability of
      these cloned receptors will enable many more studies on structure-function
      relationships for these receptors as well as clarifying their tissue
      distribution, regulation and roles in health and disease. It may also be possible
      to design novel therapeutic agents that permit manipulation of the receptors when
      their function is abnormal.

PMID- 8734455
TI  - Somatostatin receptors and disease: role of receptor subtypes.
AB  - A variety of human neuroendocrine tumours express SSTR. The five recently cloned
      human SSTR subtypes have a distinct chromosomal localization and pharmacological
      profile, and a tissue-specific expression pattern which suggests a differential
      function of SSTR subtypes in different organ systems. Most tumours carrying SSTR
      may express multiple SSTR subtypes, while the SSTR2 subtype is most predominantly
      expressed. The somatostatin analogue, octreotide, binds with high affinity to the
      SSTR2 and SSTR5 subtype and with a low affinity to the SSTR3 subtype. This
      analogue does not bind to the SSTR1 and SSTR4 subtypes. No major differences in
      the binding characteristics have been found between octreotide and two other
      clinically used octapeptide SST-analogues, BIM-23014 and RC-160. Our preliminary
      data indicate that an absent hormonal response to octreotide in vitro also
      implies an absent response to BIM-23014 and RC-160. The expression of the SSTR2
      subtype in human tumours is proposed to be related to a clinical beneficial
      effect of octreotide treatment, while the functional significance of the other
      SSTR subtypes is not clear at present. In addition it is unclear which subtype(s)
      is involved in the antimitotic actions of SST(-analogues). Further developments
      with regard to the oncological application of SST analogues await the
      identification of the SSTR subtype(s) mediating anti-proliferative effects, as
      well as the development of analogues which selectively activate this subtype(s).
      A good correlation has been found between the presence of SSTR2 subtype mRNA and
      binding of [125I-Tyr3]octreotide in human primary tumours. Therefore, SSTR
      scintigraphy of human primary tumours and their metastases presumably visualizes
      SSTR2-expressing tumours, although it is reasonable to assume that SSTR5, and to
      a lesser extent SSTR3, when expressed simultaneously with SSTR2, also contribute
      to the visualization of tumours.

PMID- 8734456
TI  - Endocrine disorders associated with mutations in guanine nucleotide binding
      proteins.
AB  - The basis for a number of relatively rare endocrine diseases, which present
      clinically with features of AHO, have been shown conclusively to result from
      mutations in the G3 alpha gene which interfere with the expression of functional
      protein. Individual kindreds display a range of specific mutations in this gene.
      A further series of disorders result from somatic mutations of the G3 alpha gene
      which result in constitutive activation (in one case probably with a concomitant
      decrease in stability of the expressed protein). When such a mutation occurs in
      early embryogenesis it can result in a pattern of mosaicism of expression of
      clinical features in the patient. Despite these cases, equivalent alterations in
      other G-protein alpha subunit genes seem to be of limited importance in human
      disease. This is despite biochemical data from a range of experimental cell
      models which indicate that such mutations can have potent effects on cell growth
      and division.

PMID- 8734457
TI  - Activities of nitric oxide in normal physiology and uremia.
AB  - Nitric oxide (NO) generated from arginine exerts a variety of renal and
      extrarenal physiological and pathophysiological effects. NO is generated by two
      types of nitric oxide synthases: acutely responsive, constitutive NOS and slower,
      more persistent inducible NOS (iNOS). The latter is transcriptionally dependent,
      often stimulated by cytokines. NO regulates glomerular ultrafiltration, tubular
      reabsorption, and intrarenal renin secretion; many of these renal effects are
      mediated by interactions with angiotensin II and adrenergic (alpha 2) activity.
      Decreased NO activity also enhances tubuloglomerular feedback activity, which
      could contribute to renal vasoconstriction, NaCl retention, and elevated blood
      pressure. Loss of renal function could influence NO activity via: (1) endothelial
      dysfunction; (2) decreased arginine synthesis by kidney; (3) responses to
      arginine analogs that act as NOS inhibitors; (4) increased cytokine activity; and
      (5) altered oxidation:reduction status of cells, etc. For example, platelet
      dysfunction in uremia may be caused by cytokine-induced iNOS activation.
      Moreover, acutely responsive, constitutive NOS activity may be depressed in
      progressive loss of renal function. Decreased NO activity might contribute to
      baroreceptor dysfunction observed in hypertension and progressive renal disease.
      Studies of the impact of uremia suggest that iNOS may be chronically stimulated
      by cytokines, whereas acutely responsive, constitutive NOS activity may be
      concurrently depressed.

PMID- 8734458
TI  - Glomerular protein trafficking and progression of renal disease to terminal
      uremia.
AB  - Experimental and human studies indicate that altered glomerular permeability to
      proteins correlates with tubulointerstitial injury and subsequent glomerular
      scarring. Maneuvers that restore the selectivity of glomerular barrier to
      macromolecules limit renal injury in progressive nephropathies. The abnormal
      traffic of proteins through the glomerular capillary has an intrinsic renal
      toxicity linked to the process of over-reabsorption by proximal tubular cells.
      Excessive protein reabsorption induces functional alterations of tubular cells
      that overexpress inflammatory and vasoactive molecules, as indicated by in vitro
      or in vivo studies. Thus monocyte chemoattractant protein-1 and osteopontin may
      attract inflammatory cells into renal interstitium. Enhanced tubular endothelin-1
      secretion, mainly toward the basolateral membrane of the cell, may stimulate
      interstitial macrophage infiltration and in addition may promote interstitial
      fibroblast proliferation and extracellular matrix synthesis, thus amplifying
      tubulointerstitial inflammation and injury.

PMID- 8734459
TI  - Metabolic acidosis as a uremic toxin.
AB  - Patients with chronic renal failure suffer from a muscle wasting syndrome that is
      characterized by loss of lean body mass and negative nitrogen balance. Evidence
      is provided indicating that metabolic acidosis plays a major role in initiating
      these adverse effects. In particular, we discuss findings suggesting that
      metabolic acidosis mitigates its effects by activating the cytosolic ubiquitin
      proteasome proteolytic pathway. Additional evidence that metabolic acidosis
      alters vitamin D and parathyroid hormone levels is provided. Therapy that
      includes correction of the metabolic acidosis with alkali in the form of sodium
      bicarbonate supplements has significant therapeutic implications for uremic
      patients with even mild degrees of metabolic acidosis.

PMID- 8734460
TI  - Organic acids and the uremic syndrome: protein metabolite hypothesis in the
      progression of chronic renal failure.
AB  - A number of organic acids including phenols are accumulated in plasma of uremic
      patients because of reduced renal clearance. Some of them account for uremic
      problems such as reduced drug binding. Protein-bound organic acids such as
      hippuric acid, indoxyl sulfate, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic
      acid (CMPF), are markedly accumulated in uremic plasma, and produce defective
      protein binding of drugs. CMPF is tightly bound to serum albumin, and thus cannot
      be removed by conventional hemodialysis, but continuous ambulatory peritoneal
      dialysis and protein-leaking hemodialysis can remove CMPF, leading to lower serum
      levels. Based on the findings that indoxyl sulfate stimulates the progression of
      chronic renal failure in rats, and that low-protein diet or oral sorbent exert
      protective effects on the progression of chronic renal failure and reduce the
      serum and urine levels of indoxyl sulfate, the author proposes a protein
      metabolite hypothesis that endogenous protein metabolites such as indoxyl sulfate
      play a significant role in the progression of chronic renal failure.

PMID- 8734461
TI  - T cells and B cells in chronic renal failure.
AB  - Recent knowledge into the pathophysiological mechanisms mediating the immune
      abnormalities characteristic of end-stage renal disease (ESRD) has focused on the
      dual activation versus deficiency state of immunocompetent cells. Despite major
      advances in renal replacement therapy, notably hemodialysis, no significant
      improvement in the immune status of uremic patients has been achieved. After a
      brief review of the role of T cells and B cells in the normal immune response,
      the functional and phenotypic T and B cell abnormalities observed in uremic
      patients are presented. Special emphasis is placed on our recent findings
      indicating that these abnormalities are observed at an early stage in the course
      of chronic renal failure, worsen with the progression of uremia, and are
      exacerbated by the dialysis procedure. The previous hypotheses that could
      reconcile the so-called Janus-faced behavior of T cells in uremia are updated in
      light of the recent findings obtained in the search of therapeutic strategies
      that could counteract the impaired responsiveness of patients with ESRD to
      vaccination against hepatitis B virus. Perspectives of research aimed at
      elucidating the respective role of T helper cell subpopulations (Th1 and Th2)
      could contribute to understanding of the mechanisms of the multifaceted process
      of uremia-related immune dysregulation and of the rationale for possible
      immunointervention strategies.

PMID- 8734462
TI  - Dysfunction of polymorphonuclear leukocytes in uremia.
AB  - There is increased incidence of infectious complications in uremic patients,
      indicating impairment of cellular host defense in these patients. Several reports
      confirm metabolic and functional abnormalities of polymorphonuclear leukocytes
      (PMNL) including altered adherence to endothelial cells, altered generation of
      reactive oxygen species, altered release of microbial enzymes, impaired
      chemotaxis, phagocytosis, intracellular killing of bacteria, altered carbohydrate
      metabolism, and/or impaired ATP formation. Several studies report on correlations
      between PMNL dysfunction, especially phagocytosis and oxidative burst, and
      ferritin content. Deferoxamine therapy improved PMNL function. Chronic renal
      failure is a state of increased cytosolic calcium. Increased cytosolic calcium is
      associated with several alterations of PMNL function and metabolism, which
      improve by normalization of cytosolic calcium either by calcium channel blockers
      or by lowering of elevated parathyroid hormone. Each hemodialysis session using
      bioincompatible membranes triggers neutrophil activation, evidenced by
      overexpression of adhesion molecules, elevation of cytosolic calcium, release of
      PMNL granular enzymes, and generation of reactive oxygen species. Several studies
      claim that this results in chronic downregulation of phagocyte function. Several
      granulocyte inhibitory compounds have been isolated and characterized from uremic
      serum. The uremic retention product p-cresol depresses respiratory burst
      activity. The following granulocyte inhibitory peptides could be isolated from
      dialysis patients: granulocyte inhibitory protein I and II with homology to light
      chain proteins and beta 2-microglobulin, degranulation inhibitory protein I and
      II being identical to angiogenin and complement factor D, and immunoglobulin
      light chains. These proteins inhibit PMNL function in nanomolar concentrations.

PMID- 8734463
TI  - Dyslipidemia in renal disease.
AB  - In summary, dyslipidemia is a common feature of various renal syndromes. Whether
      this perturbed lipid metabolism results in accelerated atherosclerosis and
      increased cerebrovascular and cardiovascular morbidity and mortality remains a
      subject of inquiry. Also undefined is the role of dyslipidemia in the progression
      of renal injury. The malnutrition that becomes a dominant morbid feature in
      patients on maintenance renal replacement therapy provides a caveat against
      aggressive intervention for modest hyperlipidemia once dialysis is instituted.
      Individualized assessment of end organ atherosclerotic disease and cardiovascular
      risk factors should form the basis for modification of the treatment plan (ie,
      pharmacological intervention) should nonpharmacological means prove ineffective.

PMID- 8734464
TI  - The heart in uremia.

PMID- 8734465
TI  - Anorexia in dialysis patients.
AB  - Malnutrition, which is common in maintenance dialysis patients, is strongly
      associated with increased morbidity and mortality. An important contributing
      factor is anorexia, leading to reduced intake in relation to the recommended
      allowances, which for protein is higher than in healthy subjects. Uremic toxicity
      in underdialyzed patients may cause anorexia as a result of retention of toxic
      compounds in the middle molecular weight range, which are normally excreted in
      the urine. Various comorbidity factors and psychosocial and economic factors may
      also be associated with low nutritional intake. The hemodialysis procedure may
      reduce nutritional intake because of cardiovascular instability with nausea and
      vomiting and post-dialysis fatigue. Abdominal discomfort, absorption of glucose
      and amino acids, and peritonitis may reduce appetite in peritoneal dialysis
      patients. Underdialysis, if present, should be corrected and various catabolic
      factors such as acidosis, infections, and other comorbidity factors should be
      treated, dietary counseling should be given, and psychosocial and economic
      support should be provided when needed. Patients who remain malnourished despite
      such measures may be given parenteral or enteral nutritional supplementation.
      Peritoneal dialysis solutions with amino acids have been used successfully in
      CAPD patients who suffer from protein malnutrition. Recombinant human growth
      hormone and IGF-1 are new treatment alternatives that need further evaluation.

PMID- 8734466
TI  - Effects of uremia on growth in children.
AB  - Growth failure is a major complication of uremia in infancy and childhood. The
      influence of the primary renal disease leading to uremic growth retardation in
      children, the contributing factors leading to growth failure, such as metabolic
      acidosis, renal osteodystrophy, hyperparathyroidism, nutrition-endocrine and
      developmental disorders, are reviewed to update nephrologists on the complex
      issue of growth failure in children with uremia. The collaboration between
      endocrinologists and nephrologists in treating children with growth retardation
      is highlighted by a recently completed National Institutes of Health (NIH)-funded
      clinical trial on renal osteodystrophy plus the use of recombinant human growth
      hormone and insulin-like growth factor. Finally, this article concludes with a
      brief summary of an approach to reverse the effects of uremia on growth,
      including conservative nutritional management, treatment of anemia with
      erythropoietin, and selected aspects of growth and development after renal
      transplantation.

PMID- 8734467
TI  - Thoughts about judging dialysis treatment: mathematics and measurements, mirrors
      in the mind.
AB  - This article considers the contributions of the urea kinetic parameters, , Kt/V
      and nPCR, to beliefs about judging dialysis treatment. The values calculated from
      any set of data depend on the model (eg, 1 pool, 2 pool, or so forth) and the
      mathematics used to derive the values. Yet, the medical community debates the
      value of Kt/V at which patients should be treated even as they debate the
      mathematics by which Kt/V should be calculated. The resulting ambiguities about
      proper targets and methods may actually frustrate large-scale clinical quality
      enhancement initiatives. The casual use of mathematical models can mislead unwary
      clinicians and compromise quality enhancement. For example, the observation that
      a high Kt/V is associated with a high nPCR leads to the widespread belief that
      improving Kt/V must substantially improve nutritional status. The association,
      however, results mainly, if not solely, from mathematical coupling rather than
      biological cause and effect. The misguided belief could contribute to ineffective
      treatment of malnourished patients. Complicated mathematical models are useful
      tools for describing and evaluating evolving concepts about the physical
      properties of dialysis and for estimating the effects of new therapies. However,
      the changing nature of concepts, and therefore the mathematical models designed
      to support them, makes clinical care ideas that attempt to shoehorn old concepts
      into new equations. It is the result of the dialysis treatment, not the
      mathematical path by which it is achieved, that is associated with improved
      patient health. Consequently, clinical care should be guided by simple
      measurements that reflect the outcome of the treatment, not by mathematical
      parameters.

PMID- 8734468
TI  - Calcium as a second messenger of the action of transforming growth factor-beta on
      insulin secretion.
AB  - In MIN6 insulinoma cells, transforming growth factor-beta (TGF-beta) induced the
      oscillatory elevation of the cytoplasmic free calcium concentration, [Ca2+]c, in
      the presence of 5.5 mM glucose. The increase in [Ca2+]c induced by TGF-beta was
      totally dependent on calcium entry and attenuated by nifedipine or nickel
      chloride. In contrast, carbachol elevated [Ca2+]c in the presence of nickel
      chloride. When the plasma membrane was hyperpolarized by diazoxide, TGF-beta did
      not raise [Ca2+]c, whereas both carbachol and depolarizing concentration of
      potassium elevated [Ca2+]c under the same conditions. TGF-beta did not affect
      either the cellular cyclic AMP or inositol trisphosphate levels. In the presence
      of 5.5 mM glucose, TGF-beta induced a 3-fold increase in insulin secretion and
      the effect of TGF-beta was blocked by either nifedipine or nickel chloride. TGF
      beta did not stimulate insulin secretion in the presence of 100 microM diazoxide,
      whereas both carbachol and 40 mM potassium chloride significantly increased
      insulin secretion. These results suggest that TGF-beta induces the oscillatory
      elevation of [Ca2+]c in MIN6 cells by stimulating calcium entry via voltage
      dependent calcium channels. Calcium is an intracellular messenger of the action
      of TGF-beta on insulin secretion.

PMID- 8734469
TI  - Effect of selective beta-adrenoceptor stimulation on UCP synthesis in primary
      cultures of brown adipocytes.
AB  - Given the co-existence of the three beta-adrenoceptor (beta AR) subtypes (beta
      1AR, beta 2AR and beta 3AR) in brown adipocytes, the present study was undertaken
      to determine the relative importance of these in the induction of UCP synthesis
      in mouse BAT precursor cells in primary culture. Cells at different stages of
      differentiation were exposed to different beta AR agonists: prenalterol (a
      selective beta 1AR agonist), salbutamol or clenbuterol (selective beta 2AR
      agonists), or BRL 37344 (a selective beta 3AR agonist). As with the endogenous
      agonist, noradrenaline, and the non-selective beta AR agonist, isoprenaline, all
      four beta AR agonists induced UCP in the confluent stage of the cells, but with
      different potencies, and with the highest induction being seen after clenbuterol
      or BRL 37344 treatment. Cells in the confluent stage of development were the most
      sensitive to the effects of the agonists, although clenbuterol and BRL 37344
      induced a weak UCP synthesis in pre-confluent cells. None of these beta AR
      agonists were able to induce UCP synthesis in the post-confluent period. The
      responses to prenalterol and salbutamol were inhibited by propranolol at
      relatively low concentrations, suggesting their effects were mediated by beta 1AR
      and beta 2AR, respectively. However, propranolol was a particularly weak
      antagonist of BRL 37344 and, unexpectedly, of the clenbuterol UCP responses,
      which suggests that both induce UCP synthesis via the beta 3AR. In summary, the
      beta 3AR is the most important adrenoceptor coupled to the induction of UCP
      synthesis, although both beta 1AR and beta 2AR activation may make a
      contribution. However, all three beta AR subtypes do not become fully functional
      until cultured cells become confluent.

PMID- 8734470
TI  - Changes in adenosine A1- and A2-receptor expression during adipose cell
      differentiation.
AB  - Two adenosine receptors A1 and A2 are associated with either stimulation (A2) or
      inhibition (A1) of adenylate cyclase. Using the clonal cell line Ob1771, we have
      studied the expression of the two receptors during the process of adipose
      conversion accelerated by exposure to dexamethasone and 3-isobutyl-l
      methylxanthine (IBMX) during the first 3 days post-confluence. The effects
      mediated by the two receptors on preadipocyte differentiation and adipocyte
      metabolism were also investigated. The two adenosine agonists NECA and PIA were
      used as preferential agonists of the A2- and A1-receptor, respectively. In
      preadipose cells (just confluent), both of the mouse clonal line and human
      primary culture, NECA dose-dependently stimulated cAMP production with a
      significant higher potency (P < 0.01) than did PIA. In adipose cells (16-day post
      confluent) NECA was found to exert a biphasic effect on forskolin-stimulated cAMP
      production: i.e., NECA was clearly inhibitory in the femto- to picomolar
      concentration range whereas this effect gradually diminished at higher
      concentrations. The effect of PIA in 16-day post-confluent adipose cells however,
      was purely inhibitory on both cAMP production (IC50: 33.52 +/- 0.44 fM) and
      lipolysis (64% +/- 7%; P < 0.01). These findings were corroborated by Northern
      blot analysis which revealed A1-receptor mRNA to be exclusively expressed in the
      mature adipocytes, whereas A2-receptor mRNA gradually declined during the
      differentiation process except in 16-day post-confluent cells. In addition, NECA
      significantly enhanced the effect of corticosterone-induced differentiation by
      46.8% (P < 0.05) but failed to have any adipogenic potency acting either alone or
      in concert with carbaprostacyclin (cPGI2). Thus, endogenous adenosine may have a
      bimodal action on adipose tissue metabolism mediated through stimulatory A2- and
      inhibitory A1-receptors, respectively, as a function of adipose conversion.

PMID- 8734471
TI  - Direct binding of progesterone receptor to nonconsensus DNA sequences represses
      rat GnRH.
AB  - The mechanisms by which steroid receptors repress gene expression are not well
      understood. In this report, we show that progesterone receptor (PR), in the
      presence of progesterone (P) directly represses rat gonadotropin releasing
      hormone (rGnRH) gene transcription. Deletion analysis studies using transient
      transfection assays in GT1-7 neuronal cells mapped the effects of P to sequences
      in the proximal rGnRH promoter between -171 and -73. This DNA sequence lacks any
      consensus steroid response element binding sites. Cotransfection of a mutant
      progesterone receptor that lacks a functional DNA binding region (hPRcys)
      abolished repression of the rGnRH promoter by P. Gel mobility shift assays
      confirmed that PR directly binds to the DNA fragments -171/-126, -126/-73, and 
      111/-73, which encompass the negative progesterone response element (nPRE) of the
      rGnRH promoter. Mutagenesis of the rGnRH nPRE -171/-126 DNA fragment resulted in
      a loss of PR binding. Thus, direct DNA binding of PR to nonconsensus elements in
      the proximal rGnRH promoter inhibits rGnRH gene expression.

PMID- 8734472
TI  - Prolactin receptor gene expression in rat splenocytes and thymocytes from birth
      to adulthood.
AB  - In vivo and in vitro studies have indicated that the anterior pituitary hormone
      prolactin (PRL) is an immunoregulator and functions in the development of the
      neonatal immune system. In this study, prolactin receptor (PRL-R) expression from
      birth to adulthood as well as the effect of milk ingestion on the PRL-R
      expression were examined in splenocytes and thymocytes of neonatal rats. Three
      approaches were taken to measure PRL-R expression: (i) polymerase chain reaction
      (RT-PCR); (ii) antibody to PRL-R and Western blotting; (iii) antibody to PRL-R
      and flow cytometry. RT-PCR analysis revealed the short and long form of PRL-R
      mRNA in both spleen and thymus at every age tested. However, the long form of PRL
      R mRNA was always more abundant than that of the short form. In addition,
      antipeptide antibody against the long form of PRL-R recognized 84 and 42 kD
      proteins in the spleen, but only the 84 kD protein in the thymus. A monoclonal
      antibody U6 recognized 38 and 40 kD proteins in both the spleen and thymus.
      Although the mRNA level of PRL-R was relatively low at birth and increased with
      age in both the spleen and thymus, the levels of protein bands detected with both
      antibodies correlated with development in the spleen; whereas the levels remained
      steady in the thymus. Therefore, we concluded that the expression of PRL-R at the
      protein level is developmentally regulated in the spleen but not in the thymus.
      Finally, milk ingestion in the first seven hours decreased the percentage of
      cells expressing cell surface PRL-R, suggesting that milk-borne PRL may have a
      direct effect on lymphocytes.

PMID- 8734473
TI  - Tyrosine kinase inhibitor as a novel signal transduction and antiproliferative
      agent: prostate cancer.
AB  - In prostate cancer cells, the binding of peptide growth factors to specific
      receptors increases tyrosine kinases (TK) activity to regulate cell
      proliferation, cell differentiation, and signaling processes. To determine
      whether inhibition of receptor TK activity inhibits tumor growth, we studied the
      effects of a tyrosine kinase inhibitor, RG-13022 (tyrphostin), on cultured human
      prostate cancer cells. RG-13022 significantly inhibited TGF alpha-induced
      phosphorylation of EGF receptor (EGFR). This compound inhibited TGF alpha
      stimulated [3H]thymidine incorporation in a dose-dependent manner with IC50 being
      30 microM. Clonogenicity in soft agar was reduced in the presence of RG-13022.
      Inhibitory effects were also observed in androgen-positive LNCaP cells and
      androgen-negative PC3 cells. RG-13022 not only inhibited TGF alpha-induced growth
      but also growth stimulated by epidermal growth factor (EGF), acidic fibroblast
      growth factor (aFGF) and serum. In addition, RG-13022 also blocked androgen
      stimulated cell proliferation, suggesting that functioning TK pathways are
      required for androgen-induced growth. This novel synthetic inhibitor may be
      useful in providing a new strategy for future therapeutic intervention for
      prostate cancer.

PMID- 8734475
TI  - Differential desensitization response of the neonatal and adult rat somatotroph
      to growth hormone-releasing hormone and phorbol ester.
AB  - Elevated levels of circulating growth hormone (GH) in the perinatal animal may be
      caused in part by relative resistance to the desensitizing effects of GH
      secretagogues. We compared the effects of 4-day exposure of primary pituitary
      cell cultures from adult male and 2-day-old rats to GH-releasing hormone (GHRH;
      10 nM) or 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 1 microM) on subsequent
      acute GH response to these secretagogues. Prolonged exposure to GHRH reduced
      subsequent GHRH-induced GH release from pituitary cells of both age groups, but
      the reduction in GH response was significantly less in neonates than adults. In
      addition, GH secretion from neonatal pituitaries rose progressively during each
      day of GHRH exposure, to reach levels almost 7 times basal; by contrast, GH
      secretion from adult pituitaries increased only transiently and then declined.
      Prolonged exposure to TPA reduced the subsequent GH response to TPA equally in
      neonates and adults, but differentially affected the GH response to GHRH; TPA
      exposure reduced the GH response to GHRH in neonates, but not in adults. These
      data suggest a fundamental difference between the GH regulatory processes of
      neonatal and adult pituitaries. The ability of the somatotroph to exhibit
      attenuated GH response on exposure to secretagogue is developmentally regulated,
      and relative resistance of the immature somatotroph to homologous desensitization
      by GHRH may contribute to elevated serum GH levels during the perinatal period.

PMID- 8734474
TI  - Effects of the N-terminal cysteine mutation on prolactin expression and secretion
      in transfected cells .
AB  - We developed an experimental cell model to look for motif(s) of rat PRL sequence
      encoding a sorting signal to secretory granules. An efficient expression vector
      (pCMV-rPRL) was used to transfect several eukaryotic cell lines in culture, i.e.,
      one neuronal cell line (C6) and three glandular pituitary derived cell lines
      (AtT20, GC, GH3CDL). Despite the ubiquitous transcription of pCMV-rPRL, the
      synthesis and secretion of rPRL were detected primarily in GH3CDL cells that
      derived from lactotrophs, suggesting a cell-specific post-transcriptional control
      of rPRL expression. During transient expression, exogenous native PRL was
      transported through intracellular compartments of the secretory pathway and
      underwent regulated release. Abolition by mutagenesis (C4S) of the N-terminal
      disulfide bond increased by 50% the PRL secretion rate (medium to cell ratio) and
      multiplied by 5 the specific activity of medium PRL from pulse-labeled cells.
      These results support the hypothesis that N-terminal disulfide bond plays a role
      in the control of PRL intracellular transit and storage.

PMID- 8734476
TI  - The extragenomic action of progesterone on human spermatozoa is influenced by
      redox regulated changes in tyrosine phosphorylation during capacitation.
AB  - Capacitation had no effect on the ability of progesterone to elicit a rapid
      calcium transient in the acrosomal domain of human spermatozoa but had a marked
      influence of the ability of this steroid to induce a biological response. The
      development of this responsiveness to progesterone appeared to be redox regulated
      in that it was promoted by the stimulation of reactive oxygen species generation
      and inhibited by the presence of antioxidants, including catalase and membrane
      permeant thiols. The ability of redox conditions to influence the biological
      responsiveness of human spermatozoa did not involve changes in the dynamics of
      the calcium transients induced by progesterone but was causally linked with clear
      differences in tyrosine phosphorylation. We conclude that the ability of human
      spermatozoa to respond to the calcium transients induced by progesterone depends
      on a background of phosphotyrosine expression that can be profoundly influenced
      by the redox status of the spermatozoa during capacitation.

PMID- 8734477
TI  - Expression of functional lutropin/choriogonadotropin receptor in the baculovirus
      system.
AB  - The LH/CG receptor (LH/CG-R) is a G protein-coupled receptor with a relatively
      large glycosylated extracellular domain. The complete 674 amino acid residue rat
      receptor was expressed in Sf9 insect cells using the baculovirus expression
      system. Optimal expression under the control of the polyhedrin promoter was
      obtained at 72 h post-infection and a multiplicity of infection of 0.1. The
      recombinant LH/CG-R was expressed on the cell surface (ca. 4500 receptors/cell)
      and exhibited saturable, high affinity binding of human CG (hCG) with a Kd of 0.4
      nM. There was no evidence of intracellular trapping of the receptor. The
      intracellular concentration of cAMP was increased in response to hCG binding. In
      contrast, baculovirus-expressed recombinant hCG only weakly stimulated
      intracellular cAMP levels at relatively high doses. Two forms of the receptor
      (approximately 75 and approximately 200 kDa) were detected by Western blot
      analysis. These results demonstrate that the full length LH/CG-R expressed in
      insect cells is functional in that it binds hormone with high affinity and is
      able to couple to adenylate cylase.

PMID- 8734478
TI  - Effect of hemorrhage and nephrectomy on erythropoietin gene expression in the
      ovine fetus.
AB  - The purposes of this study were to determine whether (1) erythropoietin (Epo)
      gene expression could be stimulated, by severe hemorrhage, in both kidney and
      liver, at three stages of gestation (75-80, 106-112, and 140-142 days; term
      approximately equal to 150 days) in chronically-cannulated ovine fetuses and (2)
      whether the liver would compensate for the lack of kidneys at 110 days. Blood was
      removed (20% of estimated blood volume) at each of 0, 1, 19 h, and tissues
      collected at 24 h. In hemorrhaged fetuses (H) the liver mRNA levels were 2.7-, 5
      , and 3-times that of control fetuses (C) at 78, 110 and 141 days, respectively.
      The kidney H:C ratios, for Epo mRNA, were 5, 6.4 and 43, respectively, at these
      three stages of gestation. In six fetuses at 108 days, nephrectomized 5-7 days
      before hemorrhage (HN) Epo mRNA increased 5-fold in the liver, and plasma Epo
      values were significantly lower (P < 0.05) than in intact (H). Thus hemorrhage
      stimulates increased Epo gene expression in both liver and kidney from mid
      gestation, in the ovine fetus, but the liver does not compensate for the lack of
      kidneys at 110 days.

PMID- 8734479
TI  - Hexamethylenebisacetamide (HMBA) is a growth factor for human, ovine and porcine
      thyroid cells.
AB  - Hexamethylenebisacetamide (HMBA) provokes in murine erythroleukemia cells (MELC)
      a commitment to terminal differentiation leading to the activation of the
      expression of hemoglobin. HMBA has been tested also in other cells from colon
      cancer, melanoma or lung cancer. However it has not yet been tested in the
      thyroid. We demonstrate in this paper that HMBA in kinetics and concentration
      response experiments increases the proliferation of human thyroid cells isolated
      from Graves'-Basedow patients. It also acts like a growth factor for ovine and
      porcine thyroid cells, respectively, from the OVNIS line and the ATHOS line. This
      molecule which is a differentiating factor in the MELC system and a growth factor
      in human thyroid cell cultures represents a potential to get human thyroid cell
      lines expressing specialized functions.

PMID- 8734480
TI  - Physiological comparison of alpha-ethyl-alpha-methyl-gamma-thiobutyrolactone with
      benzodiazepine and barbiturate modulators of GABAA receptors.
AB  - The GABAA receptor/chloride ionophore (GABAR) is allosterically modulated by
      several classes of anticonvulsant agents, including benzodiazepines and
      barbiturates, and some alkyl-substituted butyrolactones. To test the hypothesis
      that the anticonvulsant butyrolactones act at a distinct positive-modulatory site
      on the GABAR, we examined the physiological effects of a butyrolactone, a
      benzodiazepine and a barbiturate on GABA-mediated currents in voltage-clamped
      neurons and cells transfected with various subunit combinations. The
      butyrolactone, alpha-ethyl-alpha-methyl-gamma-thiobutyrolactone (alpha EMTBL),
      altered the EC50 for GABA and changed the apparent cooperativity of GABA
      responses. In contrast, the benzodiazepine chlordiazepoxide altered the EC50 for
      GABA with no effect on apparent cooperativity. The barbiturate phenobarbital
      altered both the EC50 and the amplitude of the maximal GABA response without
      altering apparent cooperativity. The GABA-mediated effect of the barbiturate, but
      not the benzodiazepine, added to the maximal effect of the butyrolactone,
      supporting the hypothesis that butyrolactones do not exert their effect at the
      barbiturate effector site. Both alpha EMTBL and phenobarbital potentiated GABA
      currents in transfected cells containing the alpha 1 beta 2 and alpha 1 gamma 2
      subunit combinations, as well as alpha 1 subunits alone. Chlordiazepoxide had the
      minimum requirement of an alpha subunit and a gamma subunit. Specific GABARs
      lacking benzodiazepine or barbiturate modulation were tested for modulation by
      alpha EMTBL. The alpha 6 beta 2 gamma 2 combination was modulated by the
      butyrolactone but not chlordiazepoxide. However, GABARs comprising rho1 subunits
      were sensitive to both phenobarbital and alpha EMTBL. Although the molecular
      determinants for alpha EMTBL action appear similar to the barbiturates, our data
      support the conclusion that alpha EMTBL interacts with GABARs in a distinct
      manner from barbiturates and benzodiazepines.

PMID- 8734482
TI  - Reduction of cerebellar GABAA responses by interleukin-1 (IL-1) through an
      indomethacin insensitive mechanism.
AB  - Recently, a role of IL-1 in the central nervous system has been described,
      principally a fever-inducing effect in the hypothalamus through a prostaglandin
      second messenger system. IL-1 has also been shown to potentiate gamma
      aminobutyric acid (GABAA) responses in embryonic chick neurones. This study
      describes the investigation of the effect of IL-1 on GABAA responses within the
      in vitro rat cerebellar slice, a preparation containing intact neuronal
      circuitry. Stimulation of the area of passage of paralleled fibres produced a
      pure GABAA inhibition of the spontaneous firing of Purkinje cells. 5 and 10 ng/ml
      IL-1 produced a reduction in the duration of inhibition 10 min after beginning
      perfusion of IL-1. This effect reversed within 15 min of washing out the IL-1. 10
      ng/ml IL-1 also reduced the effects of exogenously-applied GABA (0.1 mM) with the
      same time course. In the presence of 1 uM indomethacin, there was no change in
      the effect of the IL-1. It can therefore be concluded that the reduction in
      cerebellar GABAA responses by IL-1 is not mediated by the indomethacin-sensitive
      prostaglandin second messenger system.

PMID- 8734481
TI  - Zolpidem functionally discriminates subtypes of native GABAA receptors in acutely
      dissociated rat striatal and cerebellar neurons.
AB  - The whole-cell patch-clamp technique was used to compare the properties of native
      GABAA receptors in Purkinje and striatal neurons acutely dissociated from
      neonatal rat brains (7-11 days old). In symmetrical chloride concentrations and
      at a negative holding voltage, GABA induced inward currents in a concentration
      dependent manner with EC50 values of 4 and 8 uM in Purkinje and striatal neurons,
      respectively. Diazepam potentiated the current induced by 1 uM GABA in Purkinje
      and striatal neurons with EC50 values of 28 and 42 nM and maximal potentiations
      of 128 and 182%, respectively. Zolpidem potentiated this GABA-induced current in
      Purkinje and striatal neurons with EC50 values of 33 and 195 nM and maximal
      potentiations of 189 and 236%, respectively. These results show that zolpidem, in
      contrast to diazepam, functionally discriminates subtypes of native GABAA
      receptors. Zolpidem has greater affinity for GABAA receptors containing omega 1
      (Purkinje cells) than for those with omega 2 (striatum) sites and has higher
      intrinsic activity at these receptors than diazepam. These properties of zolpidem
      may contribute to its hypnoselective profile.

PMID- 8734483
TI  - Lamotrigine potentiates the antiseizure activity of some anticonvulsants in DBA/2
      mice.
AB  - Lamotrigine [0.5-10 mg/kg, intraperitoneally (i.p.)] was able to antagonize the
      audiogenic seizures in DBA/2 mice in a dose-dependent manner. Lamotrigine at
      doses of 0.5 and 1.25 mg/kg i.p., which per se did not significantly affect the
      occurrence of audiogenic seizures in DBA/2 mice, markedly potentiated the
      anticonvulsant activity of carbamazepine, diazepam, phenytoin, phenobarbital and
      valproate against sound induced seizures in DBA/2 mice. The degree of
      potentiation by lamotrigine was greatest for diazepam and valproate, lower for
      phenobarbital, and least for phenytoin and carbamazepine. The increase in
      anticonvulsant activity was associated with a comparable increase in motor
      impairment. However, the therapeutic index of combined treatment of diazepam +
      lamotrigine or valproate + lamotrigine was more favourable than the diazepam +
      saline or valproate + saline treatment. Since lamotrigine did not significantly
      influence the plasma levels of the anticonvulsant drugs studied we might suggest
      that pharmacokinetic interactions, in terms of total plasma levels, are not
      probable. However, the possibility that lamotrigine alters protein binding and
      increases the relative free vs protein bound ratio may not be excluded.
      Lamotrigine did not significantly affect the hypothermic effects of the
      anticonvulsant compounds studied. Lamotrigine showed an additive effect when
      administered in combination with some classical anticonvulsants, most notably
      valproate and diazepam.

PMID- 8734484
TI  - Regional changes in brain dopamine utilization during status epilepticus in the
      rat induced by systemic pilocarpine and intrahippocampal carbachol.
AB  - Systemic administration of pilocarpine (400 mg/kg i.p.) or intrahippocampal
      injection of carbachol (100 micrograms/1 microliters) induced limbic motor
      seizures in rats, characterized by head weaving and paw treading, rearing and
      falling, and forepaw myoclonus, developing into status epilepticus. After being
      in status for 30 min, rats were killed and levels of dopamine,
      dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were determined in
      eight brain regions by high performance liquid chromatography. Pilocarpine
      induced seizures significantly elevated dopamine in the striatum, and in both
      dorsal and ventral aspects of the hippocampus, but did not affect dopamine in
      substantia nigra, nucleus accumbens, olfactory tubercle, cingulate cortex or
      amygdala. Metabolite levels were increased in striatum, substantia, nigra,
      nucleus accumbens and cingulate cortex, and fell in the hippocampus, but remained
      unchanged in the olfactory tubercle and amygdala. Intrahippocampal carbachol
      significantly raised the dopamine contents of striatum and nigra, and in both
      ventral and dorsal aspects of the hippocampus, but not elsewhere. DOPAC and/or
      HVA were elevated in all brain regions tested, save for amygdala and dorsal
      hippocampus. These changes translated into seizure-induced increases in dopamine
      utilization in the nucleus accumbens, olfactory tubercle and cingulate cortex,
      and to a fall in dopamine utilisation in the hippocampus, with no net change in
      amygdala. In addition pilocarpine (but not carbachol) increased dopamine
      utilization in the nigrostriatal axis, possibly through a seizure-unrelated
      mechanism. The relevance of these findings to seizure development are discussed.

PMID- 8734485
TI  - Modification of the characteristics of dopamine transporter in brain regions and
      spinal cord of morphine tolerant and abstinent rats.
AB  - The specific binding of [3H]GBR 12935 to crude synaptosomal membranes of brain
      regions and spinal cord of morphine tolerant and abstinent rats was investigated.
      Male Sprague-Dawley rats were implanted with 6 morphine pellets each containing
      75 mg of morphine base during a 7-day period. Placebo pellet implanted rats
      served as controls. Rats sacrificed without removal of the pellet were considered
      tolerant whereas those from which pellets were removed 16 hr prior to sacrificing
      were labeled abstinent. The binding of [3H]GBR 12935 was initially determined at
      a 1 nM concentration in all brain regions and spinal cord, which was followed by
      the determination of Bmax and Kd values in the corpus striatum, a highly enriched
      region for the dopamine transporter. In morphine tolerant rats, the binding of
      [3H]GBR 12935 was increased in the hypothalamus (182%) but was decreased in the
      corpus striatum (34%) and spinal cord (30%). The decrease in binding in the
      corpus striatum was due to an increase in the Kd value of [3H]GBR 12935. However,
      during morphine withdrawal, the binding of [3H]GBR 12935 was still higher in the
      hypothalamus (255%) but was decreased in the hippocampus (53%). Thus, chronic
      administration of morphine results in changes in the dopamine transporter
      function in selected brain regions and the spinal cord, and these changes are
      dependent upon whether or not the animals are undergoing the abstinence syndrome.

PMID- 8734486
TI  - Progesterone in vitro increases NMDA-evoked [3H] dopamine release from striatal
      slices in proestrus rats.
AB  - The dopaminergic nerve terminals in rat striatum appear to be an important target
      for progesterone (Pg) and the excitatory amino acid glutamate. In the present
      study the possible interaction between glutamate and Pg upon [3H]DA release in
      striatal slices from rats in proestrus was examined. [3H]DA release was augmented
      by NMDA in a concentration-dependent manner. The presence of Pg (400 nM) in the
      perfusion medium produced an amplification of the responses to NMDA (50 microM)
      as shown by significant increase in the tritium outflow. The NMDA selective
      antagonists AP-7 (100 microM) and MK-801 (0.1 microM) prevented the effects of
      both NMDA and NMDA plus Pg on [3H]DA release. In contrast, the AMPA/kainate
      receptor antagonist CNQX (10 and 20 microM) was ineffective. Furthermore, AP-7
      (100 microM) attenuated the enhancing effect of 400 nM Pg on [3H]DA release
      evoked by 28 mM K+. The antagonist was unable to alter the effect produced by K+
      alone. These results indicate a specific action of Pg on dopaminergic terminals
      mediated by NMDA receptors and suggest a close interaction between glutamate and
      dopamine systems in the striatum, apparently modulated by progesterone.

PMID- 8734487
TI  - (+/-)-kavain inhibits the veratridine- and KCl-induced increase in intracellular
      Ca2+ and glutamate-release of rat cerebrocortical synaptosomes.
AB  - The action of (+/-)-kavain on the veratridine, monensin and KCl-depolarization
      evoked increase in free cytosolic Ca2+ concentration ([Ca2+]i), and its influence
      on the release of endogenous glutamate from rat cerebrocortical synaptosomes were
      investigated. [Ca2+]i was fluorimetrically determined employing FURA as the Ca2+
      sensitive fluorophore, and glutamate was detected by a continuous enzyme-linked
      fluorimetric assay. The incubation of synaptosomes in the presence of (+/-)
      kavain up to a concentration of 500 mumol/l affected neither basal [Ca2+]i nor
      spontaneous release of glutamate, but dose-dependently reduced both veratridine
      elevated [Ca2+]i (IC50 = 63.2 mumol/l) and glutamate-release (IC500 = 116.4
      mumol/l). The inhibition of these parameters, attained with 500 mumol/l(+/-)
      kavain, could be overcome by inducing an artificial Na+ influx, using monensin as
      a Na+ ionophore, An application of (+/-)-kavain after veratridine caused a
      decrease in veratridine-elevated [Ca2+]i, which was similar to the action of
      tetrodotoxin (TTX) with regard to time course, half-life of [Ca2+]i decline and
      the final steady state level of [Ca2+]i. Concomitantly, veratridine-induced
      glutamate-release was blocked. The results indicate that specific inhibition of
      voltage-dependent Na+ channels is a primary target of (+/-)-kavain, thus
      preventing a [Na+]i provoked increase in [Ca2+]i and glutamate-release. However,
      pathways related to the elevation of [Ca2+]i by [Na+]i itself, and the processes
      involved in normalization of elevated [Ca2+]i and glutamate-release downstream to
      enhanced [Ca2+]i, seems to be unaffected by (+/-)-kavain. Using KCl-depolarized
      synaptosomes, 400 mumol/l (+/-)-kavain reduced, in analogy to Aga-GI toxin, KCl
      evoked [Ca2+]i and diminished the part of glutamate-exocytosis which is related
      to external Ca2+ to about 75% of control. At a concentration of 150 mumol/l,
      which is above the IC50 value necessary to block voltage-dependent Na+ channels,
      (+/-)-kavain affected neither basal nor the KCl-induced increase in [Ca2+]i.
      These results might suggest that (+/-)-kavain at concentrations sufficient to
      block Na+ channels completely. moderately inhibits the non-inactivating Ca2+
      channels located on mammalian presynaptic nerve endings.

PMID- 8734488
TI  - Pressure exposure unmasks differences in release properties between high and low
      yield excitatory synapses of a single crustacean axon.
AB  - The cellular mechanisms underlying the effect of high pressure on synaptic
      transmission at two types of synapses were studied in the opener muscle of the
      lobster walking leg. Excitatory postsynaptic currents (EPSCs) were recorded using
      a loose macropatch clamp technique at normal pressure and 3.5, 6.9 MPa helium
      pressure. Responses of the single excitatory axon could be grouped into two
      types: low yield (L) synapse exhibiting a small mean EPSC with a considerable
      number of failures, and high yield (H) synapse having a larger mean EPSC with
      very few failures. The change in several synaptic transmission parameters
      indicated that high pressure similarly reduced presynaptic evoked release in both
      L and H synapses. However, some differences in the kinetics and probability of
      release could be detected. A major difference was the spontaneous miniature EPSCs
      (mEPSCs) activity. Many of the mEPSC, observed only in L synapses, were 'giant'
      (size of 2-5 q). High pressure selectively increased the frequency of the giant
      mEPSCs in the L synapse but had little effect on their amplitude histogram. High
      pressure depressed evoked synaptic transmission in both synapses by modulating
      the presynaptic quantal release parameters, but concomitantly enhanced
      spontaneous quantal release in L synapses by an unknown mechanism.

PMID- 8734489
TI  - Effects on iontophoretically applied acetylcholine on membrane potential and
      synaptic activity of bulbar respiratory neurones in decerebrate cats.
AB  - Intracellular recordings were made from bulbar respiratory neurones of
      decerebrate cats, together with iontophoretic application of acetylcholine and
      its specific antagonists to assess cholinergic mechanisms involved in the central
      respiratory network in vivo. Of 126 respiratory-related neurones impaled in the
      ventral respiratory group, iontophoresis of acetylcholine produced depolarization
      in 67 cells (53%), hyperpolarization in 36 cells (29%), and no effect in the
      remaining 23 cells (18%). Depolarization occurred predominantly in laryngeal
      motoneurones (31/40) and bulbo-spinal neurones (4/5), while a comparable number
      of non-antidromically-activated respiratory neurones displayed either
      depolarization (33/81) or hyperpolarization (31/81). Acetylcholine had no
      significant effect on excitatory and inhibitory postsynaptic potentials in all
      types of neurones tested. Both depolarizing effects of acetylcholine were
      antagonized by co-iontophoresis of atropine, but not by hexamethonium. Input
      resistance was increased (7/9) or unchanged (2/9) in depolarized cells, whereas
      it was unaltered in all hyperpolarized cells tested (n = 6). The present results
      suggest that the distribution and functions of cholinergic muscarinic receptors
      are different for the laryngeal and bulbo-spinal types of respiratory neurones
      and the non-antidromically-activated respiratory neurones in the cat.

PMID- 8734490
TI  - The effect of the selective reversible acetylcholinesterase inhibitor E2020 on
      extracellular acetylcholine and biogenic amine levels in rat cortex.
AB  - E2020 is a piperidine cholinesterase inhibitor (ChEI) which is structurally
      distinct from other compounds presently under study for treatment of Alzheimer's
      disease. We studied the effect of this compound on acetylcholine (ACh),
      norepinephrine (NE), dopamine (DA) and serotonin (5-HT; 5-hydroxytryptamine) by
      means of transcortical microdialysis in the cortex of awake rats with no ChEI in
      the probe. We also compared the inhibition of brain cholinesterase (ChE) by two
      different approaches. Following 0.5 and 2.0 mg/kg s.c. administration, the
      increase in ACh was 200% (30 min) and 2100% (1 hr), respectively. The maximal ChE
      inhibition at 30 min was 35.5% (2.0 mg/kg) and 15.6% (0.5 mg/kg) when measured as
      ACh hydrolysis in the diluted homogenate. After the 2.0 mg/kg dose,
      phosphorylation by DFP was completely blocked at 30 min. After 0.5 mg/kg, ChE
      phosphorylation was maximally inhibited at 30 min (56%) and declined thereafter
      to negligible levels by 3 hr. In addition, E2020 increased extracellular levels
      of catecholamines in cortex in agreement with our previous findings with
      carbamate ChEI. Following 2.0 mg/kg, both NE (100%) and DA (80%) were elevated,
      whereas after 0.5 mg/kg only NE (50%) was affected. Neither dose affected
      extracellular 5-HT. Thus, E2020, which inhibits brain ChE by a novel, reversible
      mechanism, elevates extracellular ACh in a comparable manner to other centrally
      active ChEI, and this elevation of ACh is associated with stimulation of
      catecholamine release.

PMID- 8734491
TI  - (-)-pindolol and (+/-)-tertatolol affect rat hippocampal 5-HT levels through
      mechanisms involving not only 5-HT1A, but also 5-HT1B receptors.
AB  - The present work examined, using in vivo microdialysis, the effects of 0.16-10
      mg/kg of the beta-adrenoceptor antagonists, (-)-pindolol and (+/-)-tertatolol,
      which have additional 5-HT1A receptor antagonist properties, on extracellular 5
      HT levels in the ventral hippocampus of chloral hydrate-anaesthetized rats. These
      effects were compared with those observed when (-)-pindolol and (+/-)-tertatolol
      were given together with the 5-HT1A agonist 8-OH-DPAT (0.31 mg/kg i.p.). When
      given alone, (-)-pindolol and (+/-)-tertatolol increased 5-HT levels not only
      after systemic administration (at 2.5 and 10 mg/kg s.c.), but also when perfused
      locally through the dialysis probe (at a concentration of 10 microM). At doses
      equal to or lower than those that increased 5-HT when given alone, (-)-pindolol
      and (+/-)-tertatolol inhibited the decrease of extracellular 5-HT levels induced
      by 8-OH-DPAT. At higher doses, however, (-)-pindolol and (+/-)-tertatolol were
      less able to reverse these effects of 8-OD-DPAT. The selective beta 1
      adrenoceptor antagonist, (+/-)-betaxolol, did not alter 5-HT levels, either when
      given alone or when given together with 8-OD-DPAT. Although the antagonism of the
      8-OH-DPAT-induced decrease of 5-HT levels by (-)-pindolol and (+/-)-tertatolol is
      likely to be related to their 5-HT1A antagonist properties, their ability to
      increase extracellular 5-HT levels when given alone may involve interactions with
      5-HT1B receptors at hippocampal 5-HT terminals.

PMID- 8734492
TI  - Autoradiographic localization of 5-CT-insensitive 5-HT1-like recognition sites in
      guinea pig and rat brain.
AB  - Quantitative autoradiographic studies, with [3H]5-HT, were used to investigate
      the distribution of 5-CT-insensitive 5-HT1-like (5-HT1E/1F) recognition sites in
      rat and guinea pig brain. For comparison and control purposes the distribution of
      the closely related 5-HT1D binding site, which is abundant in the guinea pig but
      not the rat, was also investigated, as well as total specific [3H]5-HT binding.
      Results from this study confirm the previously described regional distribution of
      the 5-HT1D binding site and also revealed a predominance of 5-CT-insensitive 5
      HT1-like 5-HT1E/1F) recognition sites in the olfactory tubercle, caudate putamen,
      nucleus accumbens and substantia nigra of both species. Interestingly 5-CT
      insensitive 5-HT1-like (5-HT1E/1F) recognition sites were particularly dense in
      the claustrum of the guinea pig, but not the rat.

PMID- 8734493
TI  - Pharmacological characterization of nitric oxide production in a rat model of
      meningitis.
AB  - Depending on its concentration and target site, nitric oxide (NO) is an
      intracellular messenger or inflammatory mediator. Recent research supports an
      expanded role for NO in the pathophysiology of neuroinflammatory diseases. Using
      analytical and pharmacological techniques, the present study identifies NO as a
      potential inflammatory mediator in experimental meningitis in the rat.
      Intracisternal administration of lipopolysaccharide (LPS) induced NO synthesis
      from the lateral and third ventricle choroid plexi and surface meninges but not
      from systemic white blood cells, suggesting that meningeal inflammation was
      restricted to the central nervous system. The time course of NO production
      revealed at 3 hr lag after intracisternal LPS, followed by a peak of 8 hr and
      subsequent decrease to baseline 24 hr after LPS dosing. The pharmacological rank
      order of NO synthase inhibitors in meningeal preparations (NG-aminoarginine > NG
      methylarginine approximately aminoguanidine) was slightly different than the rank
      order for the LPS-stimulated monocyte-macrophage cell line, J774A.1 (NG
      aminoarginine approximately NG-methylarginine > aminoguanidine). A prolonged
      inhibition of NO production was observed in cultured meningeal preparations or
      J774A.1 cells briefly exposed to and washed free from NO synthase inhibitors.
      These findings implicate NO as an inflammatory mediator during experimental
      meningitis, and suggest that NO synthase inhibitors might be potentially useful
      agents for meningeal inflammation.

PMID- 8734494
TI  - Antagonism of the presumed presynaptic action of L-AP4 on GABAergic transmission
      in the ventrobasal thalamus by the novel mGluR antagonist MPPG.
AB  - The metabotropic glutamate receptor (mGluR) agonists CCG-I and L-AP4, acting at
      Group II and Group III mGluRs respectively, can reduce GABAergic synaptic
      inhibition on single neurones in the rat thalamus in vivo via a presumed
      presynaptic mechanism. The actions of L-AP4 were antagonized by (+/-)-alpha
      methyl-4-phosphonophenylglycine (MPPG), whereas CCG-I was significantly less
      affected. Thus MPPG may be a useful tool for detecting physiological roles for
      Group III mGluRs.

PMID- 8734495
TI  - Regulation of the zebrafish goosecoid promoter by mesoderm inducing factors and
      Xwnt1.
AB  - Goosecoid is a homeobox gene that is expressed as an immediate early response to
      mesoderm induction by activin. We have investigated the induction of the
      zebrafish goosecoid promoter by the mesoderm inducing factors activin and basic
      fibroblast growth factor (bFGF) in dissociated zebrafish blastula cells, as well
      as by different wnts in intact embryos. Activin induces promoter activity, while
      bFGF shows a cooperative effect with activin. We have identified two enhancer
      elements that are functional in the induction of the goosecoid promoter. A distal
      element confers activin responsiveness to a heterologous promoter in the absence
      of de novo protein synthesis, whereas a proximal element responds only to a
      combination of activin and bFGF. Deletion experiments show that both elements are
      important for full induction by activin. Nuclear proteins that bind to these
      elements are expressed in blastula embryos, and competition experiments show that
      an octamer site in the activin responsive distal element is specifically bound,
      suggesting a role for an octamer binding factor in the regulation of goosecoid
      expression by activin. Experiments in intact embryos reveal that the proximal
      element contains sequences that respond to Xwnt1, but not to Xwnt5c. Furthermore,
      we show that the distal element is active in a confined dorsal domain in embryos
      and responds to overexpression of activin in vivo, as well as to dorsalization by
      lithium. The distal element is to our knowledge the first enhancer element
      identified that mediates the induction of a mesodermal gene by activin.

PMID- 8734496
TI  - Xenopus Xsal-1, a vertebrate homolog of the region specific homeotic gene spalt
      of Drosophila.
AB  - We have isolated an amphibian homolog of the homeotic gene spalt of Drosophila.
      Like its Drosophila counterpart the Xenopus Xsal-1 gene encodes a protein that
      contains three widely separated sets of sequence related double zinc finger
      motifs of the CC/HH-type as well as a single CC/HH zinc finger. The Xenopus gene
      encodes a fourth double zinc finger and a single CC/HC zinc finger motif that
      have no counterpart in the fly protein. Alternative splicing of Xsal-1
      transcripts gives rise to RNAs coding for either four, three or two double zinc
      fingers, respectively. The main expression domains of Xsal-1 in early development
      are confined to distinct regions along the lateral axon tracts within the
      midbrain, hindbrain, and spinal cord. Outside the central nervous system Xsal-1
      is expressed in the facio-acoustic ganglion and in the developing limb buds. The
      pattern of expression suggests that Xsal-1 might be under control of signals
      emanating from the notochord and/or the floor plate and that it might function in
      neuronal cell specification.

PMID- 8734498
TI  - The expression of a reporter protein, beta-galactosidase, is preserved during
      maturation and aging in some cells of the adult Drosophila melanogaster.
AB  - The effects of maturation and aging on cell stability and maintenance of protein
      expression have been examined in adult Drosophila melanogaster. Counting the
      number of cells present in the antenna of the adult fly revealed little loss in
      cell number with aging. Enhancer map-marked genes expressing beta-galactosidase
      (beta-gal) in the antenna and an Rh1 opsin reporter gene construct expressing
      beta-gal in the R1-6 photoreceptor cells of the compound eye revealed no
      alteration in spatial distribution or amount of beta-gal with aging. A heat shock
      inducible promoter coupled to the expression of beta-gal, hsp70-lacZ, revealed
      that the rate and amount of induction of beta-gal after heat shock is preserved
      during aging but the rate of decay of beta-gal may be slightly delayed in older
      animals. These studies suggest that the ability to express a reporter protein,
      beta-galactosidase, is preserved in at least a subset of cells in the aging fly.

PMID- 8734497
TI  - Compound mutants for retinoic acid receptor (RAR) beta and RAR alpha 1 reveal
      developmental functions for multiple RAR beta isoforms.
AB  - Mice with targeted disruptions in retinoic acid receptor genes have been
      generated to assess the role of nuclear receptors as transducers of the retinoid
      signal during vertebrate development. Mice with mutations that disrupt all
      isoforms of the RAR alpha, RAR beta and RAR gamma genes as well as for the
      individual RAR alpha 1, RAR beta 2 and RAR gamma 2 have been described. By
      breeding the RAR alpha 1 and RAR beta strains together we have generated double
      mutants which have striking phenotypes not discernible in mice homozygous for the
      individual mutations. Mice lacking both RAR alpha 1 and RAR beta died shortly
      after birth because of hypoxia, although individual RAR alpha 1 and RAR beta
      mutants were phenotypically normal. As previously observed in RAR compound
      mutants, histological examination of 18.5 dpc fetuses of RAR alpha 1 -/-beta-/-
      double mutants revealed a number of congenital malformations which in many
      respects were similar to those observed in fetuses of vitamin A-deficient
      mothers. The regions of congenital defects in RAR alpha 1 -/-beta-/- double
      mutants included the eye, the skull, the respiratory tract, the heart, the aortic
      arch-derived great vessels, and urogenital system. The penetrance of
      malformations in RAR alpha 1 -/-beta-/- mutants was greater than that in the
      reported RAR alpha 1 -/-beta 2-/- double mutants. Moreover, RAR alpha 1 -/-beta-/
      mutants exhibited hypoplastic lungs and ossified fusion between basioccipital
      and exoccipital bones that were not reported in the RAR alpha 1 -/-beta2-/-
      animals, and displayed ectopic thymus and an unique defect in testis suggesting
      specific roles for RAR beta 1, 3 and/or 4 isoforms in these structures. The RAR
      alpha 1 single mutant animals as well as RAR alpha 1-/- beta-/- double mutant
      mice were susceptible to the teratogenic effects of RA, demonstrating that RAR
      alpha 1 and RAR beta isoforms singly or in combination do not play a major role
      in RA-induced craniofacial malformation and limb deformities.

PMID- 8734499
TI  - huckebein is required for glial development and axon pathfinding in the
      neuroblast 1-1 and neuroblast 2-2 lineages in the Drosophila central nervous
      system.
AB  - huckebein encodes a predicted zinc finger transcription factor which is
      transiently expressed in a subset of Drosophila central nervous system precursors
      (neuroblasts (NBs)). We used DiI cell lineage tracing and cell fate markers to
      investigate the role of huckebein in the NB 1-1 and NB 2-2 cell lineages. Loss of
      huckebein does not switch these NBs into different NB fates, nor does it change
      the number of cells in their lineages; rather, it is required for glial
      development in the NB 1-1 lineage, and for axon pathfinding of a subset of
      interneurons and motoneurons in both lineages.

PMID- 8734500
TI  - Olfaction in birds: differential embryonic expression of nine putative odorant
      receptor genes in the avian olfactory system.
AB  - We have isolated nine putative odorant receptor genes from the chick, named COR1
      to COR9, that belong to the large multigene family of olfactory G protein-coupled
      receptors found in the fish, rat, mouse, dog, and human. By combining genomic DNA
      blot analysis, low stringency library screenings, and several PCR analyses, we
      were able to detect approximately 20 COR genes in the chick genome highly related
      to COR1-9. By in situ hybridization of newborn and adult, COR expression was
      detected only in the olfactory epithelium, and exhibited a random spatial
      distribution. During development, COR expression was observed as early as
      embryonic stage E5. Different levels of gene expression were observed for the
      COR1-9 genes: at E5, COR1-6 expression was high compared to the expression of
      COR7, COR8, and COR9. Surprisingly, at E5, a row of COR1-6 positive cells
      probably associated with the olfactory nerve extended outside the olfactory
      placode, reaching the anterior pole of the developing forebrain. These results
      suggest that, in addition to their role as putative odorant receptors, some COR
      may play a role in the development of the avian olfactory system.

PMID- 8734501
TI  - Cell fate and morphogenetic movement in the late mouse primitive streak.
AB  - A prospective fate map of the late gastrulation mouse primitive streak has been
      charted in 8.5 dpc mouse embryos developed in culture, using the lineage marker
      DiI to label groups of cells. As at earlier stages, the fate of cells in the 8.5
      dpc primitive streak is regionalised such that successively more caudal regions
      of the streak give rise to more lateral mesoderm. While most labelled cells over
      a 24 or 48 h culture period exit from the primitive streak, some are consistently
      found to remain within it. The most conspicuous resident population is present in
      the node. To determine when ingression of ectoderm through the streak ceases,
      ectoderm cells of the streak and posterior neuropore of 8.5-10.0 dpc embryos were
      labelled. Involution of surface cells to form mesoderm continues until closure of
      the posterior neuropore but is not seen thereafter.

PMID- 8734502
TI  - Checklist: vertebrate homeobox genes.
AB  - Up to now around 170 different homeobox genes have been cloned from vertebrate
      genomes. A compilation of the various isolates from mouse, chick, frog, fish and
      man is presented in the form of a concise checklist, including the designations
      from the original publications. Putative homologs from different species are
      aligned, and key characteristics of embryonic or adult expression domains, as
      well as mutant phenotypes are briefly indicated.

PMID- 8734503
TI  - Sheep cloned using embryos derived from a cultured cell line.

PMID- 8734504
TI  - Nuffield Council cautiously approves xenotransplantation using pigs.

PMID- 8734505
TI  - Serological survey for orthopoxvirus infection of wild mammals in areas where a
      recombinant rabies virus is used to vaccinate foxes.
AB  - Several fox vaccination campaigns against rabies have been undertaken in Belgium
      by using a vaccinia-rabies recombinant virus distributed in baits in the field.
      However, foxes and other wild animals that may ingest the baits could be infected
      at the same time by another orthopoxvirus, such as cowpox virus, which circulates
      in wildlife. Recombination between the two viruses could therefore occur. A
      serological survey for antibodies to orthopoxvirus, and particularly to cowpox
      virus, was undertaken in foxes and in several other wild species. Antibodies were
      detected only in two rodent species, in 16 of 25 bank voles (64 per cent) and in
      two of 29 woodmice (7 per cent). The risk of virus recombination in wildlife can
      therefore be considered to be extremely low.

PMID- 8734506
TI  - Bovine adenovirus type 10: properties of viruses isolated from cases of bovine
      haemorrhagic enterocolitis.
AB  - The isolation, serological classification and growth properties of adenoviruses
      isolated from fatal cases of haemorrhagic enterocolitis in calves are described.
      Four viruses, from different submissions, were isolated in cultures of calf
      testis cells and were identified as adenoviruses by electron microscopy. The four
      isolates were serologically identical and were classified as bovine adenovirus
      type 10 in cross-neutralisation tests with other bovine, ovine and porcine
      adenovirus species. Their growth in the nucleus of infected cells was accompanied
      by the production of typical adenovirus-associated inclusions. A serological
      survey to determine the incidence of infection with the virus in cattle in
      Northern Ireland demonstrated the presence of low levels of neutralising
      antibodies in 55 per cent of cattle over two years old, although only 8 per cent
      were positive at a 1/500 dilution of serum.

PMID- 8734507
TI  - Side effects of oral antimicrobial agents in the horse: a comparison of
      pivampicillin and trimethoprim/sulphadiazine.
AB  - To evaluate the side effects of oral pivampicillin and trimethoprim/
      sulphadiazine, 200 horses receiving these antimicrobial agents were studied. The
      horses received either trimethoprim/ sulphadiazine (30 mg/kg twice daily) or
      pivampicillin (25 mg/kg twice daily) for three or more days. No adverse effects
      other than loose faeces and diarrhoea were detected. The risk of diarrhoea was
      significantly less after the oral administration of pivampicillin (3 per cent)
      than after trimethoprim/ sulphadiazine (7 per cent). Horses whose appetite was
      reduced appeared to be predisposed to develop diarrhoea after the administration
      of either oral antimicrobial agent.

PMID- 8734508
TI  - Survey of Ehrlichia canis antibodies among dogs in Israel.
AB  - A seroepidemiological survey was made of the prevalence of antibodies reactive
      with Ehrlichia canis in stray and pet dogs from five geographical regions of
      Israel. Serum samples from 410 dogs were assayed by an indirect fluorescent
      antibody test and serum reactive at a 1:20 dilution or greater was considered
      positive. The overall seroprevalence was 30 per cent with 23.9 per cent in pet
      dogs and 37.5 per cent in stray dogs. The seroprevalence in apparently healthy
      pets (17.6 per cent) was lower but did not differ significantly from the
      seroprevalence in sick animals (26.6 per cent). The seroprevalence was highest in
      the north of Israel and lowest in the central hilly area, and followed the same
      trend in both the populations sampled. Young dogs (under one year old) had a
      lower seroprevalence (14.9 per cent) than adult (one to eight years) (36.4 per
      cent) or older dogs (over eight years) (34.2 per cent). The results demonstrate
      that dogs in Israel are extensively exposed to E canis and indicate that
      ehrlichiosis is endemic in this area of the Middle East.

PMID- 8734509
TI  - Atypical lymphosarcoma in a cow.

PMID- 8734511
TI  - Bovine embryo transfer.

PMID- 8734510
TI  - Sudden death in lambs associated with Clostridium sordellii infection.

PMID- 8734513
TI  - Milking machines and mastitis.

PMID- 8734512
TI  - Control of lungworm.

PMID- 8734514
TI  - Inflammatory syndrome of footpads in puppies and AA-amyloidosis.

PMID- 8734515
TI  - First conference on foundations of information science: from computers and
      quantum physics to cells, nervous systems, and societies.

PMID- 8734516
TI  - Cross-scale information processing in evolution, development and intelligence.
AB  - Biological systems are treated as percolation networks in which processes at all
      scales participate. Macroscopic inputs are transduced to microphysical events
      through an interleaved hierarchy of structures and processes and microphysical
      events are amplified to control macroscopic structures and functions. Integrity
      and adaptation are achieved through self-consistency dynamics operating at all
      levels of organization. The unmanifest structure of the vacuum plays a vital role
      in these dynamics.

PMID- 8734517
TI  - Internalist stance and the physics of information.
AB  - Information is by itself intrinsically diachronic, whereas synchronic information
      conceived by referring to an invariant source matrix of information is no more
      than a theoretical artifact constructed in the limit of ignoring the historicity.
      Information is the basic attribute of local dynamics of internal measurement, in
      which any dynamics is taken to proceed through detection internal to interacting
      material participants of whatever kind. Information dynamics of a local character
      is semantic by virtue of constructing the global principle of conservation of
      energy from the inside. Material embodiment of information actualizes in the form
      of energy consumers acting toward the outside from their inside. Global dynamics
      such as mechanics is simply a phenomenon emerging from information dynamics.

PMID- 8734518
TI  - Self-modifying systems: a model for the constructive origin of information.
AB  - The mechanisms of information processing in Turning machines and biological
      systems are examined from the point of view of physical sets of variables.
      Computation is characterized as a process, the realization of which involves a
      bounded set of interactions and a pre-definable set of variables in real systems.
      Using ideas from process philosophy, the ability of natural systems to transcend
      these computational modes is discussed. A class of systems, called self-modifying
      systems, that utilize persistent shifts in their defining interactions and
      variable composition is introduced. Various other ideas that lead to similarly
      non-computational or semi-computational scenarios (as in the case of distributed
      code systems) are referenced. As applications, computer models of emergent
      phenomena using randomly growing interaction sets as well as theoretical issues
      that range from the meaning of simulation to the problem of information gain in
      self-modifying systems are discussed.

PMID- 8734519
TI  - Tree and loop as moments for measurement.
AB  - Biologically motivated computing presents us with a measurement process in
      science. It triggers an epistemological shift from state-oriented physics to
      measurement-oriented physics, in which we can find a parallelism with
      Wittgenstein's shift from rule following to a language game. We argue here that
      an approximation or computing process can be viewed as a language game and
      propose an idea of proto-computing which is metaphorically formalized through
      disequilibration between tree- and loop-program, as a model for measurement
      oriented computing.

PMID- 8734520
TI  - Information as a basic property of the universe.
AB  - A theory is proposed which considers information to be a basic property of the
      universe the way matter and energy are. Operationally--just as energy is defined
      in terms of its capacity to perform work--so is information defined in terms of
      its capacity to organize a system. Pure energy can perform no 'useful' (entropy
      reducing) work without a concomitant input of information. Conversely, all
      expenditures of energy lead to a reorganization of the universe, hence to a
      change in its information status. Energy and information are interconvertible;
      physicists have been able to ignore the information parameter principally for two
      major reasons. First, historically, just as there was no need to define energy
      prior to the advent of increasingly complex, powered machinery and cannons
      (Galileo was a military engineer), so was there no need until the 20th Century to
      define information. It was the telephone engineers who first preoccupied
      themselves with developing a theory of information. The second reason is that
      physicists invented accounting devices such as potential energy and entropy to
      explain the apparent disappearance of energy yet maintain the law of the
      conservation of energy. The proposed theory would consider that what is conserved
      is the sum of information and energy. The mathematical relationship between
      information and entropy is provided by the equation: I = (Io)e-S/k while the
      conversion of energy into information involves the relationship: 1 J/degree K =
      10(23) bits (approximately) Acceptance of the theory would require paradigm
      shifts in a number of interrelated areas.

PMID- 8734521
TI  - Information and uncertainty in living systems, a view from ecology.
AB  - The organization of living entities combines, in close proximity and partial
      overlap, dissipative and self-organizing systems. Their superposition, in which
      gradients of opposite signification cross, allows local discontinuities to occur,
      and in them a place for marginal chaos and fractal configurations. Among other
      features, a difference in turnover speed characterizes such coupling, higher on
      the relatively more uniform domain where entropy increases more easily, and lower
      at the more minutely organized places of preferential information accretion. At
      the level of elementary physical events, logical aspects of indeterminacy could
      perhaps be clarified by an observer, assuming that the living system performs the
      role of a witness of historical progress.

PMID- 8734522
TI  - The enzymatic basis of information processing in the living cell.
AB  - Analogies are drawn between the computational aspects of information processing
      and the enzymatic events of cellular metabolism. The origin thereof is linked to
      the logic-elements involved in the reaction-diffusion processes of the metabolic
      operation. It is shown how such function entails a 'molecular machine' quality
      when associated with organized non-equilibrium energy sources in the cell.

PMID- 8734523
TI  - Metaphors, models and bioinformation.
AB  - The notion of bioinformation is central to the biosciences. This short paper
      examines a number of metaphors which are intimately related to this idea. These
      include metaphors about 'system' as well as metaphors associated with biosystem
      as 'text'. A framework its presented which allows ideas about biosystems and
      computer systems to be displaced and a number of specific topics are then
      discussed. Firstly, information processing in non-neural tissues is given as an
      example of parallel distributed processing. This is followed with a number of
      metaphors associated with 'text', including 'glue', 'verbs' and 'interpretation'.
      The paper concludes with a proposal on how to integrate general ideas of
      bioinformation using the idea of the 'ecology of domains'.

PMID- 8734524
TI  - 'Gloom in the society of enzymes': on the nature of biological information.
AB  - Most approaches to information pay attention only to the 'positive' or
      constructive side ('presence') of this phenomenon: its composition, construction
      rules, emergence, effective activity, etc. However, the 'negative' or degrading
      aspects ('absences', disappearance of activity) are equally important within most
      biologico-informational processes. In fact, protein degradation can be put on a
      par with protein synthesis concerning its functionality and sophistication. By
      taking into account recent integrative discoveries in the molecular biology of
      the cell (signalling system, cell cycle, apoptosis, protein degradation, enzyme
      function) a wider approach encompassing both the 'presence' and 'absence' aspects
      seems possible. The overall dynamics which emerges--involving symmetry breaking
      and symmetry restoration by means of information processing mechanisms--may be
      extrapolated to neuronal and socio-economic realms too. Interestingly, the
      phenomenon of 'absence' can also be pinpointed, at least as a metaphor, within
      the internal structure of natural numbers.

PMID- 8734525
TI  - Cell molecular computers and biological information as the foundation of nature's
      laws.
AB  - It is proposed to unite the principles of new science mathematics, physics and
      biology for the description of living creatures. Such description is based on
      four principles: minimal price of action, optimum prediction, minimal
      irreversibility, and causality. In this new knowledge of nature not only the
      molecular biological experimental aspects have to be considered, but also the
      profound 'meaning' of molecular texts of DNA.

PMID- 8734526
TI  - The brain as a hermeneutic device.
AB  - An attempt has been made to reconcile the 'device approach' and the
      'philosophical approach' to the brain. Systems exhibiting high structural and
      dynamic complexity may be candidates of being hermeneutic devices. The human
      brain, which is a structurally and dynamically complex device, not only perceives
      but also creates new reality: it is a hermeneutic device.

PMID- 8734527
TI  - Vertical information flow in the brain: on neuronal micro events and
      consciousness.
AB  - The consciousness problem and its relation to theories of spontaneous brain
      activity are discussed. It is argued that an evolutionary perspective suggests an
      interactionist solution of the consciousness problem, i.e., mental events
      interact with physical brain events. A specification of the physical events
      assumed to be associated with mental events is proposed to make the discussion of
      mind-brain theories more fruitful. An interactionist solution of the
      consciousness problem requires random spontaneous brain activity. A mechanism for
      such activity is proposed on the basis of experimental findings. Some new results
      from patch-clamp experiments on intact tissue (the hippocampal slice preparation)
      are presented. The results indicate that single channel events may cause random
      spontaneous neuronal activity, illustrating the phenomenon of micro events
      inducing macro or global brain events, and also the central theme of vertical
      information flow. The findings highlight the importance of understanding the
      stochastic nature of channel gating.

PMID- 8734528
TI  - The psychobiology of mind-body communication: the complex, self-organizing field
      of information transduction.
AB  - The current information revolution in molecular biology has important
      implications for an new understanding of the phenomenology of mind, memory and
      behavior as a complex, self-organizing field of information transduction. This
      paper traces the pathways of information transduction in life processes from the
      molecular-genetic level to the dynamics of mind and behavior together with
      suggestions for future research exploring the psychobiology of mind-body
      communication and its implications for the psychotherapeutic arts of the future.

PMID- 8734529
TI  - Consciousness, privacy, and information.
AB  - The challenges for a scientific study of conscious experience are discussed, as
      well as the importance of such research for the foundations of information
      science. A three pronged approach to the investigation of consciousness and its
      functions is suggested.

PMID- 8734530
TI  - Ultraperspective and endophysics.
AB  - Ultraperspective is the capability of human beings to step into the shoes of
      another person. Endophysics is the science of those physical properties of the
      world which exist not from the outside but only form the inside. Both have in
      common the adoption of an 'exterior' position. In the one case, the exteriority
      is 'horizontal', in the other, 'vertical'. Ultraperspective is a macroscopic
      concept, endophysics a microscopic one. Both can be implemented in computer
      models. Novel experiments can be set up in either domain: animals acquiring the
      status of human persons, and objective features of the physical world acquiring
      the status of an observer-specific mirage. Mead an Levinas, and Einstein and
      Bohr, are the protagonists. In the age of computer-assisted enlightenment, a new
      look at the ethical roots of science appears justified.

PMID- 8734531
TI  - A note on information, order, stability and adaptability.
AB  - This brief essay explores some of the subtler ramifications of the notion of
      order or information. It starts out by arguing that and why a system's
      information or order must be one of the central determinants of its power and
      productivity, hence of its capacity to survive. Furthermore, such information
      must also underlie a system's stability and adaptability. And this again leads us
      to what may well be one of the main laws or non-linear relationships underlying
      the growth of information or order: an increase in a system's information or
      order is more likely as its initial level of order is already higher.

PMID- 8734532
TI  - Defining systems based on information exchange: structure from dynamics.
AB  - We take the occasion of the workshop to examine a proposition that systems may be
      better defined in terms of interactions based on information exchange rather than
      on atomic elements. Although speculative, the paper is in the spirit of
      exploration within a workshop atmosphere. It is enough for us that the
      interactions be perceived to exist. On this basis, components become interactors,
      which signal each other through the exchange of information mediated by some
      interaction mechanism. At a minimum, interactions need only be imputed.
      Consequences for the appropriate definition of a system parameter based on our
      position are examined. Possible mathematical avenues are introduced. In the
      process, a connection with belief systems is explored.

PMID- 8734533
TI  - A dynamical model of the meaning of information.
AB  - The main challenge for information science is to naturalize the semantic content
      of information. This can only be achieved in the context of a naturalized
      teleology (by 'teleology' is meant the coherence and the coordination of the
      physical forces which constitute the living state). Neither semiotics nor
      cybernetics are capable of performing this task, but non-equilibrium
      thermodynamics and non-linear dynamics may be. A physical theory of the meaning
      of information is sketched, first by identifying biofunctions with generalized
      non-linear oscillators and their associated phase-space attractors, and then by
      postulating the existence, within all such oscillators, of a component capable of
      coordinating low-energy interactions with the correct environmental conditions
      supporting the dynamical stability of the oscillator. The meaning of information
      is thus interpreted as the prediction of successful functional action.

PMID- 8734534
TI  - Emergent information. Towards a unified information theory.
AB  - This paper proposes the restoration of information theory by means of a
      philosophy of evolutionary systems. What this philosophy implies for the
      conception of information may be called a multi-stage model, comprising both the
      history and the ordering of information processing by real-world systems. Such a
      unifying information concept may assist suitable research in the coming field of
      information science.

PMID- 8734535
TI  - Information in social systems: implications for steering and regulation.
AB  - The concept of information seems applicable to investigate the internal
      organization of social systems, and specifically, to give insight into the
      possibilities as well as the limitations of processes of 'steering and
      regulation'. It can play a crucial role in linking the structure of a social
      system to its actual capacity to steer and regulate its internal organization.
      Moreover, it seems promising in the understanding and explanation of the global
      dynamics of these social processes.

PMID- 8734536
TI  - C3: information science in uniform.
AB  - This contribution explores an aspect of information science, which is little
      treated in the literature, but on which enormous sums of money are spent
      annually. This is the subject of information and the prosecution of war. What
      follows may be considered as a kind of tutorial on this huge, but poorly
      understood realm of information science applications. My objective at the
      workshop was to acquaint the participants with an overview of how information has
      been woven into the fabric of conflict. At present, information is so tightly
      woven with combat that the term information warfare has been coined. It may come
      as a surprise to think in these terms about information science.

PMID- 8734537
TI  - Realities of virtual reality.

PMID- 8734538
TI  - Second-order texture contrast resolves ambiguous apparent motion.
AB  - When a black and a white square on a grey surround exchange places, it was
      previously shown that on a dark surround it is the white square, and on a light
      surround it is the black square, that is seen in apparent motion (AM). Thus the
      higher-contrast square carries the AM. We now show that the same is true for
      second-order AM of texture-defined squares. Squares were defined by four
      different textures: by anisotropy (horizontal versus vertical random dashes), by
      alpha numeric letters, by hash marks, or by dot size. The result was that the
      square that differed more from the surround in texture properties carried the
      second-order AM. Judgments of texture salience revealed a high correlation
      between salience and apparent motion. In a third experiment, crossover AM between
      dissimilar textures was investigated, and it was found that the more salient
      textures carried the AM. Results cannot be explained by the concept of "texture
      activity', but instead indicate that the system extracts a measure of "texture
      contrast' prior to analysis of salience and apparent motion.

PMID- 8734539
TI  - The perceived direction of textured gratings and their motion aftereffects.
AB  - The stimuli in these experiments are square-wave luminance gratings with an array
      of small random dots covering the high-luminance regions. Owing to the texture,
      the direction of these gratings, when seen through a circular aperture, is
      disambiguated because the visual system is provided with an unambiguous motion
      energy. Thus, the direction of textured gratings can be varied independently of
      grating orientation. When subjects are required to judge the direction of
      textured gratings moving obliquely relative to their orientation, they can do so
      accurately (experiment 1). This is of interest because most studies of one
      dimensional motion perception have involved (textureless) luminance-defined since
      wave or square-wave gratings, and the perceived direction of these gratings is
      constrained by the aperture problem to be orthogonal to their orientation. Thus,
      direction and orientation have often been confounded. Interestingly, when
      subjects are required to judge the direction of an obliquely moving textured
      grating during a period of adaptation and then the direction of the motion
      aftereffect (MAE) immediately following adaptation (experiments 2 and 3), these
      directions are not directly opposite each other. MAE directions were always more
      orthogonal to the orientation of the adapting grating than the corresponding
      direction judgments during adaptation (by as much as 25 degrees). These results
      are not readily explained by conventional MAE models and possible accounts are
      considered.

PMID- 8734540
TI  - Spatial filtering and the Zollner-Judd geometrical illusion: further studies.
AB  - In a geometrical figure in which long vertical lines are each crossed by a series
      of short oblique lines, an illusory effect is obtained such that the orientations
      of the long lines are perceived as nonvertical and shifted away from the
      orientation of the oblique lines (the Zollner illusion). In addition, the
      vertical separation between the crossing (oblique) lines is perceived as less
      than that if the crossing lines are horizontal (the Judd illusion). It has
      previously been shown that these two effects are closely related, and a single
      process account has been proposed in which both effects are explained by a
      computational model involving band-pass spatial filtering of the figure by means
      of difference-of-Gaussians (DOG) filters. Two arguments are presented against the
      latter account. First, in an opposite-contrast-polarity figure with, for example,
      white vertical lines and black crossing lines on a mid-grey background, the peaks
      in the DOG filter output are such as to predict the reversal of the Zollner-Judd
      effects. It is shown by demonstration that this prediction is disconfirmed, and
      that the normal effects are obtained. Second, it is shown that the normal Zollner
      Judd effects are obtained in the absence of the long vertical lines, and in the
      presence of anomalous contours. The latter effects are also in contradiction to
      the band-pass-filtering model. These findings are discussed in relation to a dual
      process account of the Zollner-Judd effects.

PMID- 8734541
TI  - Adaptation to spatial offsets.
AB  - After prolonged viewing of a three-element target in which the middle element is
      spatially offset, subsequent viewing of the same three elements in alignment
      results in the middle element appearing to be offset in the opposite direction.
      This adaptational aftereffect to a spatial offset was investigated with elements
      which were spatial-frequency narrowband and equidetectable to ascertain (a) the
      properties of the mechanisms involved and (b) the nature of the underlying
      computation. Evidence is presented in favour of an orientational-grouping, rather
      than a purely positional computation, underlying this aftereffect. A dual site of
      adaptation is proposed: one which receives input from the orientation extracted
      from the output of linear filters, and another which receives input from the
      orientation derived from grouping processes working on the contrast-energy
      representation. These may correspond to the mechanisms which are thought to
      underlie the processing of real and subjective contours.

PMID- 8734542
TI  - Capacity limitations in memory for visual locations.
AB  - This paper examines people's ability to make judgments which require them to know
      the relative positions of objects that are not simultaneously visible is
      examined. It has previously been shown that people can accurately perform such a
      task. The current experiments test the capacity limits for such tasks. Two
      experiments were conducted that required subjects to make spatial judgments based
      on sequences of points presented two at a time. It was shown that, whereas
      subjects can perform accurately when memory for a small number of dots (about
      four) is required, increasing the number of dots results in a radical reduction
      in performance. This argues against both the idea that spatial memory is based on
      a linguistic description and the idea that it is based on an image-like
      representation. Rather it appears that one can form an accurate representation of
      the spatial properties of a small number of objects.

PMID- 8734543
TI  - Foreshortening in cube drawings by children and adults.
AB  - The lengths of lines and the sizes of angles were measured in freehand drawings
      of cubes produced by 190 children and 158 adults. The lengths of oblique lines
      depicting receding cube edges were foreshortened relative to horizontal lines
      showing nonreceding edges. In the drawings from children aged 9 and 10 years the
      obliques were foreshortened by about 40%, compared with 30% in adults' drawings.
      The amount of foreshortening was not correlated with the angle at which the
      obliques were drawn. Line lengths were also foreshortened in "transparent"
      drawings, which are often said to show "what is known" about cube structure. One
      explanation of the results is that line lengths are foreshortened by children and
      adults to create the visual impression of equal-length cube edges, even in
      transparent drawings. This foreshortening fits with how the receding edges of a
      square face of a cube project to a vantage point. Children and adults who use
      foreshortening are not depicting the structure of cubes by matching features such
      as equal-length edges with similar features in the physical lines on the page, as
      has been suggested in some recent approaches to drawing development.

PMID- 8734544
TI  - Life-span development of odor identification, learning, and olfactory
      sensitivity.
AB  - In the first of three studies, children (aged 8 to 14 years) were found to
      perform worse than young and middle-aged adults in unprompted identification of
      doors, with average performance much like that of elderly adults. Comparisons on
      other tasks, specifically odor threshold, prompted odor identification, and
      object naming (Boston Naming Test), across the life span (five groups) revealed
      that children have the same excellent olfactory sensitivity as young adults and
      merely lack odor-specific knowledge that accumulates slowly through life. Such
      knowledge apparently accumulates so slowly that age-associated discriminative
      losses, measurable by early middle age, begin to wear away gains obtained through
      experience before odors can become overlearned. In the second study, a novel
      adaptive psychophysical method, the step procedure, confirmed the equivalent
      sensitivity of children and young adults. In the third study, a paired-associate
      task illustrated the sluggish course of odor learning. Young adults outperformed
      children, though the youngest group, first graders, made up ground relatively
      fast. For children and adults, common odors facilitated performance relative to
      novel odors. The outcome highlighted the relevance of semantic factors in odor
      learning irrespective of age.

PMID- 8734545
TI  - Can reflections on 20 years of searching.

PMID- 8734546
TI  - The effects of neglect on academic achievement and disciplinary problems: a
      developmental perspective.
AB  - The present study examines the effect of child neglect, alone and in combination
      with abuse, on academic achievement and school disciplinary problems for
      elementary, junior high, and senior high students. The sample included 324
      neglected children and adolescents, and a matched nonmaltreated sample of 420
      children and adolescents. All subjects were in grades K through 12 in a small
      city in New York state. The results revealed that neglected children did perform
      more poorly than their nonmaltreated counterparts, having lower grades, more
      suspensions, more disciplinary referrals, and more grade repetitions, even when
      controlling for gender of child and SES. Neglect alone and neglect in combination
      with physical or sexual abuse was related to lower grades and more suspensions.
      The combination of abuse and neglect had a particularly strong effect on the
      number of disciplinary referrals and grade repetitions. Abused/neglected students
      in junior high had the highest number of grade repetitions. The number of
      disciplinary referrals continued to increase through senior high for both
      neglected and abused/neglected students. Interestingly, the academic performance
      of all subjects dropped during junior high. Neglect and neglect in combination
      with abuse appeared to exacerbate a decline in academic performance that occurs
      as children enter junior high school.

PMID- 8734547
TI  - What can child homicide rates tell us about the effectiveness of child welfare
      services?
AB  - This paper examines the methodological problems involved in using child homicide
      rates as measures of the success or failure of child protection efforts. A
      comprehensive review of child homicide research identifies three major
      methodological issues: (1) The classification of child deaths as homicides is
      unreliable; (2) child homicides may not generally represent the endpoint of a
      continuum of violence ranging from inadequate parenting to maltreatment to death;
      and (3) child homicides are not frequent enough occurrences to effectively
      measure the impact of child welfare services and policies. We conclude that while
      improved reporting and classification procedures may lead to some useful avenues
      for research, relying on child homicide statistics to evaluate child welfare
      services may contribute to further narrowing the scope of child welfare by
      stressing procedures geared primarily to preventing child homicides. Child
      welfare services need to develop outcome measures that tap the broader mandate of
      improving the circumstances and well-being of children.

PMID- 8734548
TI  - Court-ordered assessment: impact of maternal noncompliance in child maltreatment
      cases.
AB  - Parental noncompliance to court orders is associated with several factors that
      jeopardize safe and stable child care. We advanced three hypotheses: (1) maternal
      noncompliance to court-ordered assessment is associated with loss of child
      custody; (2) noncompliance is related to court clinic custody recommendations;
      and (3) noncompliance is stable across child protection and court clinic
      settings. Based on a sample of 56 court-referred child maltreatment cases, all
      hypotheses were confirmed. Results are discussed in terms of: (a) maternal
      noncompliance as a marker for high-risk child care; (b) our limited understanding
      of the phenomenal meaning of noncompliance; and (c) the dearth of empirically
      derived intervention methods.

PMID- 8734549
TI  - Onset of physical abuse and neglect: psychiatric, substance abuse, and social
      risk factors from prospective community data.
AB  - Studies of psychiatric and social risk factors for child maltreatment have been
      limited by retrospective methodologies and reliance on officially reported or
      identified samples. Using data from both Waves I and II of the National Institute
      for Mental Health's Epidemiologic Catchment Area survey, 7,103 parents from a
      probabilistic community sample who did not self-report physical abuse or neglect
      of their children at Wave I were followed to determine the risk factors
      associated with the onset of self-reported physical abuse or neglect identified
      at Wave II. Social factors considered included age, socioeconomic status, social
      support, education, household size, and gender. In addition, several psychiatric
      disorders, including substance abuse disorders and depression were examined. Risk
      models were developed using hierarchical logistic regression. Physical abuse and
      neglect were found to have distinct sets of risk factors, with minimal overlap
      between the groups. Social and demographic variables were found to be limited
      predictors of maltreatment, while substance abuse disorders were strongly
      associated with the onset of both abuse and neglect (relative risks = 2.90 and
      3.24 respectively). Depression was found to be a strong risk factor for physical
      abuse (relative risk = 3.45). Implications of the findings are discussed in terms
      of major causal models of maltreatment.

PMID- 8734550
TI  - Innovative models for rural child protection teams.
AB  - This paper describes child protection teams in rural Newfoundland and Labrador,
      Canada. The teams have developed an innovative model that encourages a community
      based response to child abuse. Child protection teams usually follow the case
      consultation model, which is a group of professionals dealing with specific cases
      of child abuse. In Newfoundland and Labrador, child protection teams evolved away
      from this type of approach. Communities in the province face unique social and
      economic conditions and as a result child protection teams now mainly focus on
      prevention through public education and awareness, advocacy, and professional
      development. Many of the child protection teams have developed a two-tiered
      model. The first tier of the team includes community representatives who
      participate in the activities listed above. The second tier is involved with case
      conferences and is composed only of professionals dealing directly with the cases
      of child abuse. This paper discusses the child protection team model emerging in
      Newfoundland and Labrador in contrast to those described in the literature.

PMID- 8734551
TI  - Reliability and validity of a measure of sexual and physical abuse histories
      among women with serious mental illness.
AB  - OBJECTIVE: The purpose of this paper is to describe a standardized questionnaire
      of histories of abuse among women with serious and persistent mental illness, and
      to assess its test-retest reliability and its validity. METHODS: Seventy women
      enrolled in an outpatient clinic were asked about childhood histories of physical
      and sexual abuse in a structured clinical interviews at two times. RESULTS: Test
      retest reliability yielded a Kappa of .63 for the measure of physical abuse, and
      .82 for the measure of sexual abuse. Validity, assessed as consistency with an
      independent clinical assessment, showed 75% agreement for reports of physical
      abuse, and 93% agreement for reports of sexual abuse. CONCLUSIONS: Childhood
      histories of physical and sexual abuse can be reliably and validly assessed in
      women with severe and persistent mental illness using a standardized instrument.

PMID- 8734552
TI  - A comparison of the childhood experiences of convicted male child molesters and
      men who were sexually abused in childhood and claimed to be nonoffenders.
AB  - Eighty-four incarcerated child molesters and 95 nonoffender comparison subjects
      were interviewed. All of the nonoffenders and 93% of the child molesters had been
      sexually abused in childhood. The prisoners were more socially disadvantaged as
      children and had received more verbal and physical abuse. The prisoners were more
      accepting of their abuse in the sense of not understanding or accepting that it
      was aberrant behavior but rather thinking that it was a commonplace, inevitable,
      and consequently a normal part of childhood. Liking some aspect of the initial
      abuse also differentiated prisoners from the nonoffenders. Prisoners were abused
      by a larger number of people than were nonoffenders. Prisoners did not use the
      fact of their own abuse as an excuse for their own offenses. Abuse by a female
      was more common in the prisoner group. It is possible to see what constitutes
      sexual abuse to an outsider being construed positively by some victims,
      especially where the sexual acts occur in a context that includes affection and
      attention. This factor seems important to remember when trying to understand the
      replication of abuse across generations. The men who were least damaged by abuse
      were those abused by strangers in "one-off" offenses, which they recognized as
      wrong and from which they escaped without accepting responsibility for the adults
      behavior.

PMID- 8734553
TI  - Before Mary Ellen.

PMID- 8734554
TI  - Parental social isolation.

PMID- 8734555
TI  - Child maltreatment: testing the social isolation hypothesis.
AB  - Several barriers limit our attempts to untangle the social context of child
      maltreatment. One major barrier is our inability to agree on or effectively
      communicate what social isolation is. In an attempt to clarify this construct,
      the introductory section traces the evolution of the social isolation construct
      over the last three decades and concludes it is not one etiologic factor for
      child maltreatment, but rather, a large set of variables linked to the parent's
      perception of support, and their informal and formal networks. The empirical
      section examines each component of the social isolation construct by comparing
      300 maltreating and nonmaltreating low-income mothers. Considerable variation is
      found between the networks of different types of maltreating mothers and
      nonmaltreating mothers on structural network properties, perception of support,
      and the types of resources they do and do not receive. For example, neglectful
      mothers had fewer network members, fewer contacts, fewer members living within 1
      hour, and received fewer emotional and instrumental resources. Despite these
      findings, the label "social isolation" may not accurately describe the networks
      of mothers who maltreat their children, since all three types of maltreaters had
      at least eight important network members and more than 100 contacts with these
      members in the month before completing the questionnaire.

PMID- 8734556
TI  - Effects of aging on P3 components of somatosensory event-related potentials
      elicited by different stimulus conditions. Conventional averages and single-trial
      analysis.
AB  - Effects of aging on P3 components of somatosensory event-related potentials
      (ERPs) under different stimulus conditions were studied in healthy subjects using
      conventional averages and single-trial waveform analysis. The P3 component
      elicited by target stimuli (target P3) and that elicited by rare nontarget
      stimuli (nontarget P3) showed significant latency prolongation with age at the
      rate of 1.6 and 2.0 ms/year, respectively. The nontarget P3 showed a greater
      trial-to-trial fluctuation of single-trial latency than the target P3, probably
      because 'passive attention' was more liable to fluctuate. The variabilities of
      single-trial target P3 latency and of single-trial nontarget P3 latency were not
      correlated with age. Thus, the P3 latency prolongation with age might not be
      attributable to fluctuation in latency resulting from impairment of attention
      with aging.

PMID- 8734557
TI  - Effect of chronic cadmium exposure on VEP and EEG spectral components.
AB  - Pregnant swiss albino rats were divided to three groups as control (C), cadmium
      (Cd) and non-cadmium (NCd) groups. Control animals were received tap water while
      the rats of Cd group were received Cd as CdC12 in their drinking water during the
      experimental period. On the other hand, the NCd group was given Cd during
      pregnancy, but given tap water after birth. Twenty-two days after birth, fourteen
      rats (for each group) were taken from their mothers and continued to be treated
      with Cd (Cd group) or tap water (C and NCd groups) for an additional 38 days.
      After the experimental period, flash VEPs and EEGs of three groups were recorded
      and amplitude spectral analysis was computed by Transient Response-Frequency
      characteristics (TRFC) method. The mean amplitude (dB) of 1-3.5 and 14-20 Hz
      frequency bands for right response whereas 1-3.5, 4-7, 8-13 and 14-20 Hz
      frequency bands for left response of VEPs were decreased in Cd group compared
      with control group. On the other hand, significant differences were observed
      between Cd and control groups in all the frequency bands of EEGs except 6-8 Hz.

PMID- 8734558
TI  - Directional changes in neutrophil adherence following passive resting versus
      active imagery.
AB  - This study was designed to determine whether increases or decreases in neutrophil
      adherence could be achieved following a self-regulation (relaxation/imagery)
      intervention. Fifteen subjects were randomly assigned to one of three conditions.
      Two experimental groups employed imagery focussed on either increasing or
      decreasing neutrophil adherence. Subjects had two weeks of self-regulation
      practice (4 total training sessions) prior to blood drawings. A third group of
      control subjects had the same number of resting sessions without imagery
      training. All subjects had blood samples collected before and after either 30
      minutes of self-regulation or resting practice for two sessions. Pulse and
      peripheral finger temperature measures were taken before and after the blood
      samples. Both experimental groups demonstrated decreases in neutrophil adherence,
      and the control showed a tendency toward increases in this measure. The
      psychophysiologic data for the control group was suggestive of a relaxation
      response. The experimental group that attempted to increase neutrophil adherence
      demonstrated psychophysiologic responses that were contrary to relaxation. We
      concluded that an active cognitive exercise or process is associated with
      decreases in neutrophil adherence irrespective of the exercise. In contrast,
      relaxation without an active imagery exercise was associated with increases in
      neutrophil adherence. The results of this study are discussed in terms of
      behavioral engineering of directional immune changes.

PMID- 8734559
TI  - Diagnosis, physiology, pathology and rehabilitation of traumatic brain injuries.
AB  - Accumulating clinical and experimental studies continue to elucidate and further
      define the significance of intra- and extra-cranial factors which determine
      outcome of traumatic brain injury. These factors include severity of injury, age
      of the patient, presence or absence of premorbid brain insults, and associated
      pathophysiological events such as anoxia, respiratory arrest, hemorrage, edema,
      contrecoup and Wallerian degeneration. Following resolution of acute temporary
      symptoms, delayed complications include seizures, neurotic and psychotic
      disorders, earlier onset of stroke, earlier senescence, increased suicide risk,
      reduced life expectancy, progressive intellectual deterioration and development
      of symptoms comprising the post-traumatic syndrome. In spite of these diverse
      initial and later pathological sequelae, the reserve capacities of the brain for
      establishment of compensatory mechanisms can provide bases for a remarkable
      degree of spontaneous cerebral reorganization and recovery. The accumulating
      findings in patients with traumatic brain injuries reflect principles and factors
      underlying the organization, disorganization and reorganization of human brain
      function.

PMID- 8734560
TI  - Neuropsychological aspects of Wilson's disease.
AB  - A consecutive series of 34 patients with confirmed diagnoses of Wilson's disease
      (WD) was administered complete neuropsychological examinations upon admission to
      a university medical center for routine laboratory tests. Twenty-five patients
      with neurological and/or hepatic symptoms (symptomatics) revealed frequent and
      severe motor deficits and infrequent and mild cognitive deficits in contrast to
      nine patients with genetic findings of Wilson's disease but no symptomatic
      findings (asymptomatics). Somato-sensory tests were normal in all. One of the
      most intriguing findings was the absence of a significant correlation between the
      level of copper toxicity and the degree, nature, and frequency of associated
      neurological deficits in both symptomatic and asymptomatic patients. Fifty per
      cent of the present sample received psychiatric treatment, including
      hospitalization, for schizophrenia, depression, anxiety, and related disorders
      prior to confirmed diagnosis of WD. The present findings provide additional
      evidence that patients with the initial presenting psychological symptoms may be
      easily misdiagnosed and mistreated if the possibilities of Wilson's disease are
      not ruled out first.

PMID- 8734561
TI  - The attentional system in brain injury survivors.
AB  - The present study was designed to check the model of attention proposed by Posner
      and Petersen (1990), in patients with traumatic brain injury. We analyzed a
      series of neuropsychological tests administered to these patients after they were
      discharged from the hospital. Scores obtained from this group were subjected to
      factor analysis. The results of this analysis could be characterized by four
      factors which accounted for 85.4% of the variance. According to our data, factor
      1 (perceptual and motor speed) and factor 2 (vigilance and alertness) represent
      Posner's posterior attention system. Factor 3 (encoding) and factor 4 (shifting)
      represent Posner's anterior attention system (AAS), but we have to consider that
      the AAS is not only attention but is shared by other cognitive processes. The
      results also suggest that the attention system could be stable and could be
      defined independently from the type of patient and type of illness.

PMID- 8734562
TI  - Time perception as a complex functional system: neuropsychological approach.
AB  - Ninety-two brain-damaged patients and 111 normal control subjects were tested on
      their orientation to date; sequencing of events; discrimination of simultaneity
      and succession; conditioning to time; comparison, production and reproduction of
      durations; conservation of velocity in clocks; construction of time units; and
      psychological time. Temporal disorientation was related to advanced age, low
      educational level, amnesia, dementia and limbic or diffuse brain lesions. Only
      multifocal-diffuse lesions accompanied by dementia could disintegrate the concept
      of metric time, while sparing psychological time, discrimination of durations and
      sequencing of canonically recurring events. Reproduction of durations and
      verbally mediated temporal conditioning were impaired in frontal and temporal
      limbic lesions, which left intact the concept of time. The results support the
      hypothesis that temporal perception is accomplished by a complex functional
      system, regarding both its psychological structure and cerebral organization.

PMID- 8734563
TI  - Sleep in healthy elderly subjects: a 24-hour ambulatory polysomnographic study.
AB  - It is still debated whether the deterioration of the sleep pattern, frequently
      reported by elderly subjects, is due only to aging per se. Other factors
      associated with aging or modifications of biological rhythms could also be
      involved. Elderly subjects frequently complain of daytime sleepiness, but it is
      not clear whether this actually represents a return to a polyphasic structure of
      sleep, or only a consequence of a disturbed night sleep. Ten healthy, independent
      and active elderly subjects (age > 72 years) were elevated by means of 24-hour
      ambulatory polysomnography. Findings of nocturnal sleep were compared with sleep
      of the same group in the 24-hour period and with sleep of young healthy controls.
      We observed a fragmentation of nocturnal sleep, but a fairly good representation
      of stages and a preservation of cyclicity. Except for three cases, with early or
      late times of sleep onset and wake-up, sleep disruption did not seem to be
      related to modification of circadian rhythms. Only three subjects presented
      undesired daytime naps, whereas the others either did not show daytime sleep at
      all, or were used to having their siesta after lunch since their young adulthood.
      In normal aging, daytime sleep does not constitute a social problem. Ambulatory
      polysomnography is a valid alternative to laboratory recordings in the
      identification of daytime sleep.

PMID- 8734564
TI  - Abnormalities of ABR and auditory perception test findings in acquired palatal
      myoclonus.
AB  - An auditory test battery consisting of pure tone audiometry, the auditory
      brainstem response (ABR), the nonsense monosyllable perception test, the dichotic
      listening test and the Token test were administered to three patients with
      palatal myoclonus. All patients had ABR abnormalities correlated with the
      location of brainstem lesions, despite relatively normal pure-tone threshold. In
      two of the three patients, both the nonsense monosyllable test and the dichotic
      listening test revealed dominance on the side ipsilateral to the lesion, while
      ABR abnormalities were present on the contralateral side. In one patient who had
      bilateral ABR abnormalities, both the monosyllable perception and dichotic
      listening test scores were poor for bilateral ears. These results suggest that
      brainstem lesions producing palatal myoclonus could have an effect on auditory
      perception.

PMID- 8734565
TI  - Diagnostic agreement in the classification of headache using Ad Hoc Committee and
      IHS criteria.
AB  - This study examined the level of agreement between raters in the diagnosis of
      headache using the Ad Hoc Committee (AHC) on the Classification of Headache and
      the Headache Classification Committee of the International Headache Society (IHS)
      classification criteria. In addition, differences in classification of headache
      between the AHC and IHS classification systems were considered. Analyses
      indicated that both the AHC and IHS classification systems were adequate in
      allowing clinicians to reach 100% agreement in diagnosis of headache cases (N =
      36). Additionally, there was 91.7% diagnostic agreement between the two sets of
      criteria as applied by the raters. Differences in diagnostic classification
      between the two sets of criteria were believed to be the result of IHS
      exclusionary criteria in the classification of Tension-type headache.

PMID- 8734566
TI  - Interdependence of priming performance and brain-damage.
AB  - Basically, two hospitalized patient groups were a variety of different learning
      situations which are subdividable into conventional and experimental tests and
      which covered so-called implicit and explicit memory tests. Furthermore, data
      from other cases were used for comparison and for support of the proposed
      hypotheses. The main sample consisted of 15 focal brain-damaged patients (group
      N) and 15 patients after surgical interventions outside the nervous system (group
      O). Aside from affective behavior and intelligence, memory tests were used. These
      included the WMS-r, picture and face recognition tests, the Tower of Hanoi, the
      Wisconsin Card Sorting Test (WCST), a Concept Comprehensive Test, and word and
      picture priming tests. A number of significant differences were obtained between
      the two age, sex, and education matched groups. Above all, intelligence and
      memory were reduced in parallel in the cortically damaged compared to the well
      matched orthopedic group, while attention and concentration did not differ. Even
      performance in tests such as the Tower of Hanoi and the WCST differed, perhaps
      explainable by the proportion of frontal lobe damaged patients and the overall
      decrease in intelligence in group N. Verbal priming was found to a similar degree
      in both groups. On the other hand, priming of incomplete pictures was
      significantly poorer in group N than in group O; furthermore, results from MQ-
      and IQ-based group splitting (independent of their previous N or O affiliations)
      suggested a direct relation between mnemonic and other cognitive abilities and
      success in priming. As perceptual, but not verbal priming differed between
      groups, and explanation of group N results, based primarily on explicit memory
      processing, is unlikely. It is concluded that non-brain damaged patients in
      general are able to use a wider repertoire of information encoding strategies
      which at least in part is memory and intelligence correlated.

PMID- 8734567
TI  - Invincible Athletics program: aerobic exercise and performance without strain.
AB  - This study compared physiologic pattern during conventional aerobic exercise to
      those during Invincible Athletics--a program emphasizing balance and comfort
      during exercise to increase strength, endurance, and mind-body coordination
      gradually without the negative effects of the stress/recovery cycle. While heart
      rats were similar during both workouts, during Invincible Athletics: (1)
      perceived comfort tended to be higher and perceived exertion tended to be lower;
      (2) breath rates were significantly lower; (3) respiratory sinus arrhythmia and
      central-parietal alpha relative power were significantly higher; and (4)
      endurance was significantly longer. Respiratory sinus arrhythmia decreases with
      physiologic and mental stress. Heightened respiratory sinus arrhythmia and EEG
      alpha relative power along with subjective reports of greater comfort, less
      exertion, and observed increased endurance suggest that during Invincible
      Athletics athletes may be more easily adapting to the demands made upon them.

PMID- 8734568
TI  - Collagen-induced arthritis in mice: synergistic effect of E. coli
      lipopolysaccharide bypasses epitope specificity in the induction of arthritis
      with monoclonal antibodies to type II collagen.
AB  - DBA/1 mice develop a chronic peripheral arthritis after immunization with type II
      collagen termed collagen-induced arthritis. We have localized the main
      arthritogenic determinants of CB11, a CNBr-generated arthritogenic fragment of
      chick type II collagen (CII), using 3 smaller peptide fragments of CB11 generated
      by endoproteinase LysC, LysC1 (CII 124-290), LysC2 (CII 291-374) and LysC3 (CII
      375-402) and a panel of monoclonal antibodies (mAb) specific to CB11. MAb
      specific to the arthritogenic region of CB11 were also used to study the
      synergistic effect of E. coli lipopolysaccharide (LPS) on antibody-mediated
      arthritis in naive DBA/1 mice. LysC2 contained a minimum essential arthritogenic
      fragment of type II collagen: LysC2 induced arthritis by active immunization,
      also, a combination of four mAb specific to LysC2 passively transferred arthritis
      to naive mice. A single i.p. injection of LPS (50 micrograms/mouse) reduced the
      threshold values of the arthritogenic dose of mAb from 1 mg to 50
      micrograms/clone per mouse, and decreased the number of mAb required for inducing
      arthritis from 4 to 2 clones. These observations suggest that LysC2, an 84 amino
      acid residue fragment, contains the main arthritogenic determinants within chick
      CB11. Importantly, LPS, a strong inducer of pro-inflammatory cytokines, negates
      the required multiple epitope specificity of autoantibodies in the passive
      transfer model and acts synergistically in the induction of arthritis by
      autoantibody.

PMID- 8734569
TI  - T cells from BB-DP rats show a unique cytokine mRNA profile associated with the
      IDDM1 susceptibility gene, Lyp.
AB  - Diabetes prone biobreeding rats display several abnormalities in T cell numbers,
      T cell function and T cell surface phenotype which are associated with the onset
      of spontaneous disease. One of the most pronounced abnormalities in these animals
      is a marked T cell lymphopenia which is evident in both CD4+ and CD8+ peripheral
      T cell subsets. To gain a better understanding as to the nature of T cell
      responses in these animals, we have utilized RT-PCR to analyze the cytokine mRNA
      profiles of mitogen activated peripheral T cells derived from lymphopenic and non
      lymphopenic animals. Our results suggest that inheritance of the lymphopenia
      gene, Lyp, is associated with a unique cytokine profile most similar to that
      previously described for mouse medullary thymocytes. In addition, cell surface
      staining of peripheral T cells from diabetes prone animals revealed a high
      frequency of Thyl+ cells, which is characteristic of both thymocytes and recent
      thymic emigrants. Following thymectomy, T cell responsiveness to a number of
      different stimuli is greatly reduced on a cell for cell basis as is the absolute
      number of surviving T cells. Taken collectively, our results suggest that the
      majority of the peripheral T cell pool in these diabetic prone rats consists of
      short lived, recent thymic emigrants which most likely also contain the effector
      cells required for initiation of diabetes.

PMID- 8734570
TI  - Concentric fibrosis and cellular infiltration around bile ducts induced by graft
      versus-host reaction in mice: a role of CD8+ cells.
AB  - We report in this paper on obvious fibrotic lesions in the liver of mice
      undergoing specified graft-versus-host reaction (GVHR). B6 CD8+ splenocytes were
      transferred into (bm 12 x bm 1)F1 mice to induce GVHR. Recipient mice had been
      thymectomized and administrated with anti-CD8 monoclonal antibody (mAb) to
      deplete CD8+ cells from the hosts. Two weeks after the mAb administration,
      recipient mice were injected with B6 CD8+ cells and sacrificed further two or
      four weeks later for analyzing hepatic lesions histopathologically. Light
      microscopic analyses revealed the presence of concentric fibrosis around both
      small and large duct levels and the infiltration of mononuclear cells into portal
      areas. Focal necrosis of hepatocytes was also detected electron-microscopically.
      These findings suggest that CD8+ T lymphocytes might play an important role in
      the induction of fibrotic lesions in the liver.

PMID- 8734571
TI  - Therapy of streptozotocin induced diabetes with a bifunctional antibody that
      delivers vinca alkaloids to IL-2 receptor positive cells.
AB  - IVA039.1 is a bifunctional antibody with specificity for the murine IL-2 receptor
      and vinca alkaloids. Biodistribution studies show that IVA039.1 can target and
      deliver vinca alkaloids to tissues that contain IL-2 receptor positive cells.
      Vinca alkaloids are lymphocytotoxic. Therapy of diabetic mice with IVA039.1 plus
      vincristine results in a significant decrease in the glucose levels of diabetic
      compared to untreated mice. The therapeutic effect of IVA039.1 plus vincristine
      therapy was additive but surprisingly not synergistic. The binding of IVA039.1 to
      vincristine has moderate affinity with a slow off rate. In vitro studies suggest
      that, when bound to IVA039.1, the vincristine is inactivated. We attribute the
      lack of an enhanced therapeutic response to bifunctional antibody therapy using
      IVA039.1 plus vincristine to the inaccessibility of the drug to the target cells.

PMID- 8734573
TI  - Progress in thyroid-associated ophthalmopathy.

PMID- 8734572
TI  - T cell proliferative responses to glutamic acid decarboxylase-65 in IDDM are
      negatively associated with HLA DR3/4.
AB  - Based on studies in spontaneously non-obese diabetic (NOD) mice, it has been
      suggested that the Mr 65,000 isoform of glutamic acid decarboxylase (GAD65) is of
      major importance in the pathogenesis of insulin-dependent diabetes mellitus
      (IDDM). In humans, antibodies to GAD65 are present before and at onset of the
      disease and in vitro T cell reactivity to GAD has also been reported. To further
      characterize the T cell recognition of GAD65, we incubated peripheral blood
      mononuclear cells from 45 newly diagnosed IDDM patients with purified recombinant
      human islet GAD65 and correlated the proliferative response with HLA DR haplotype
      and the presence of GAD65 autoantibodies. Fifty healthy individuals were studied
      as controls. Of the patients, 49% showed proliferative responses to GAD65 in
      contrast to only 4% of the controls. T cell proliferation to GAD65 was
      significantly more frequent in patients not being HLA DR3/4 heterozygous (19/29,
      66%) as compared to HLA DR3/4 heterozygous patients (3/16, 19%) (p < 0.01). The
      difference was most pronounced in females with 64% (9/14) of the HLA non-DR3/4
      patients being positive compared to none (0/6) of the HLA DR3/4 patients (p <
      0.05). The overall frequency of GAD65 autoantibodies was 71% (32/45) with a
      similar distribution between patients with HLA DR3/4 (10/16, 63%) and HLA non-DR
      3/4 (22/29, 76%). There was no correlation between levels of the T and B cell
      responses to GAD65 (r = 0.24). In conclusion, we find a proliferative T cell
      response to GAD65 in approximately 50% of recent onset IDDM patients and
      unexpectedly find the majority of responders to be HLA non-DR 3/4 heterozygous
      patients. No difference was observed in B cell responsiveness between the two HLA
      groups.

PMID- 8734574
TI  - Design and implementation of a picture archiving and communication system: the
      second time.
AB  - This report describes the authors' experience in the design and implementation of
      two large scale picture archiving and communication systems (PACS) during the
      past 10 years. The first system, which is in daily clinical operation was
      developed at University of California, Los Angeles from 1983 to 1992. The second
      system, which continues evolving, has been in development at University of
      California, San Francisco (UCSF) since 1992. The report highlights the
      differences between the two systems and points out the gradual change in the PACS
      design concept during the past 10 years from a closed architecture to an open
      hospital-integrated system. Both systems focus on system reliability and data
      integrity, with 24-hour on-line service and no loss of images. The major
      difference between the two systems is that the UCSF PACS infrastructure design is
      a completely open architecture and the system implementation uses more advanced
      technologies in computer software, digital communication, system interface, and
      stable industry standards. Such a PACS can withstand future technology changes
      without rendering the system obsolete, an essential criterion in any PACS design.

PMID- 8734575
TI  - Picture archiving and communication system bandwidth and storage requirements.
AB  - The purpose of this work was to determine the requirements for image storage and
      network bandwidth for a total digital department in a moderate sized academic
      radiology department. Data from the radiology information system was combined
      with image production information to produce a model of image acquisition.
      Destinations of images to reading rooms were studied to determine the final
      distributions of film. All findings were used to model the flow of data that
      would be expected if the images in the department were completely digital. Using
      today's standards, the department would produce approximately 15.7 Gbytes of data
      per day or 3.5 Tbytes of data per year if all acquisitions were digital. The peak
      acquisition rate would be 1.8 Gbytes per hour with a sustained rate greater than
      1 Gbyte per hour for most of the working day. The anticipated bandwidth for the
      total digital department exceeded the capabilities of the existing picture
      archiving and communication system equipment. A distributed networked archive
      solution was shown to optimize access to images by radiologists and referring
      clinicians.

PMID- 8734576
TI  - Modular extension of the ACR-NEMA DICOM standard to support new diagnostic
      imaging modalities and services.
AB  - The American College of Radiology-National Electrical Manufacturers Association
      (ACR-NEMA) Standard for Digital Imaging and Communications in Medicine (DICOM)
      (NEMA PS3-1993, DICOM) enables interconnection of imaging equipment and exchange
      of diagnostic images over standard networks. The widespread adoption of DICOM by
      industry and the benefits of standardized image management have attracted
      international attention. Other medical specialties, dentistry, and veterinary
      medicine have indicated strong interest in extending the DICOM Standard to
      support nonradiological image modalities. Parts 1 through 9 of DICOM were
      published in 1992 and 1993. Additional features developed in response to requests
      from the user community are being added in DICOM Supplements. The ACR, NEMA, and
      committees from other medical specialties working under the coordination of the
      American National Standards Institute Healthcare Informatics Standards Planning
      Panel Message Standards Developers Subcommittee Joint Working Group for
      Diagnostic Image Communication have defined new image object classes to support X
      Ray Angiography, Radio-Fluoroscopy, Positron Emission Tomography, Endoscopy, and
      Light Microscopy. ACR-NEMA has also developed new service classes for Storage
      Commitment and Worklist Management. In joint work with the standards development
      committee of the Japanese Industries for Radiation Apparatus and the Japanese
      Medical Information System Development Center, ACR-NEMA has developed
      specifications for multibyte character set support and for a DICOM file format
      for transportable media. Other work is in progress. New DICOM features have
      provided and can continue to provide significant new functionality for digital
      image management systems. The demonstrated capability of efficient extension of
      the base standard is evidence of the effectiveness of the object oriented
      strategy of DICOM.

PMID- 8734577
TI  - Circumferential measurement of thoracic wall using a standard respiratory belt.
AB  - Respiratory gating during imaging to reduce imaging artifacts involves the
      gathering of image data only at the end of the respiratory cycle. This is
      commonly performed by a pneumatic respiratory belt to monitor thoracic wall
      motion during respiration. Such gating has been used for magnetic resonance,
      computerized tomographic, and nuclear medicine imaging. The goal of this study
      was to measure the performance of a standard belt used for gating imaging
      studies. The standard respiratory belt system provided with the Magnetom 42 SP
      MRI scanner (Siemens AG, Erlangen, Germany) was selected. The belt was connected
      to a microcontroller-based pressure measurement unit that was connected to the
      standard RS-232C serial port of a computer. The signal was compared with that of
      a strain gauge respiration transducer. The response of the system was tested in
      vitro both for isometric and isotonic loading. The data measured from the
      pneumatic belt was linear with different weights of 50 to 1,400 grams with a
      coefficient of determination (R2) of 0.999. The system was linear for different
      amounts of stretching (R2 of 0.998) within the first 45 mm, which is enough for
      normal breathing. In vivo the pneumatic system seemed more accurate in measuring
      the constant stretching in apnea than the strain gauge respiratory belt. The
      results show that it is possible to use a standard pneumatic belt for accurate
      measurement of thoracic wall movement during imaging and for other purposes as
      well.

PMID- 8734578
TI  - Equipment configuration and procedures: preferences for interventional
      microtherapy.
AB  - Magnetic resonance imaging (MRI), computed tomography, and electron beam
      tomography scanners are built for radiologic diagnosis. With increasing frequency
      they are being used in the field of interventional Microtherapy to permit
      transparent visualization of the therapeutic field. Each of these scanners can be
      combined with endoscopy, fluoroscopy/digital subtraction angiography, and
      ultrasound units for hybrid imaging techniques as well as with therapeutic
      systems like lasers or radiofrequency. MRI affords 3D localization without x-ray
      exposure. Open access and keyhole imaging allow nearly real time guidance of
      instruments. Minimally invasive techniques using endoscopes and hybrid
      tomographic guidance result in improved tip tracking of microinstruments and
      reduced complications. This safer access into the body will lead to
      interdisciplinary cooperation with the potential for large cost reductions. This
      report summarizes our experience regarding which of the hybrid imaging suites is
      best suited for procedures including among others drug instillations, prosthesis
      (stent) implantation, or microoperations (endoscopic diskectomy/sequestrectomy),
      and physiological measurements simultaneously.

PMID- 8734579
TI  - Conditions for the induction of long-term potentiation in layer II/III horizontal
      connections of the rat motor cortex.
AB  - 1. The present studies investigated conditions for the induction of long-term
      potentiation (LTP) in the local horizontal pathways of layers II/III in the
      primary motor cortex (MI) of the adult rat. Field potential and intracellular
      recordings demonstrated synaptic interactions across the superficial layers
      within MI that could be enhanced transiently by focal application of the gamma
      aminobuturic acid-A receptor antagonist bicuculline methiodide (Bic) at the
      recording site. 2. Field potentials evoked in the superficial MI horizontal
      pathways increased in amplitude after tetanizing, theta burst stimulation (TBS),
      but only when Bic was applied transiently at the recording site immediately
      before TBS. In the absence of Bic, TBS failed to produce long-lasting increases
      in horizontally evoked field responses. By contrast, TBS delivery during focal
      Bic application increased field potential amplitudes by 25-35% when measured 25
      30 min after stimulation. The amount of potentiation was greater when two
      converging horizontal inputs were stimulated together but was not increased with
      higher intensity stimulation. Persistent effects of Bic application alone were
      evident. However, these effects were small unless Bic application continued until
      evoked field potential amplitude increase exceeded 200% of baseline. 3. The
      synaptic nature of field potential increases were confirmed using intracellular
      recordings of layer II/III neurons located near field potential electrodes. 4.
      LTP also could be induced without Bic application by cotetanization of vertical
      pathways simultaneously with horizontal activation. Vertical conditioning alone
      at 2 Hz, which affects inhibitory efficacy, was shown to transiently relieve
      depression of successive responses that ordinarily occurs during a burst of three
      horizontal stimuli. These results suggest that LTP of horizontal pathways may be
      regulated by spatiotemporal interactions between horizontal and vertical
      pathways. 5. Horizontal LTP was blocked reversibly by bath application of the N
      methyl-D-aspartate (NMDA) antagonist 2-amino-5-phosphonovaleric acid, thereby
      implicating NMDA-receptor activation in LTP induction for these pathways. 6. The
      results confirm and extend our previous finding that the potential for activity
      dependent modification of synaptic connections exists within the intrinsic
      horizontal connections of the superficial cortical layers. Synaptic modification
      across horizontally connected neurons appears to be regulated both by the
      arrangement of intrinsic circuitry and by the availability of mechanisms for
      modification at individual synapses. The properties of horizontal connections
      indicate that they form a spatial substrate and provide an activity-dependent
      mechanism for plasticity of adult cortical representations.

PMID- 8734580
TI  - Encoding of binocular disparity by simple cells in the cat's visual cortex.
AB  - 1. Spatiotemporal receptive fields (RFs) for left and right eyes were studied for
      simple cells in the cat's striate cortex to examine the idea that stereoscopic
      depth information is encoded via structural differences of RFs between the two
      eyes. Traditional models are based on neurons that possess matched RF profiles
      for the two eyes. We propose a model that requires a subset of simple cells with
      mismatched RF profiles for the two eyes in addition to those with similar RF
      structure. 2. A reverse correlation technique, which allows a rapid measurement
      of detailed RF profiles in the joint space-time domains, was used to map RFs for
      isolated single neurons recorded extracellularly in the anesthetized paralyzed
      cat. 3. Approximately 30% of our sample of cells shows substantial differences
      between spatial RF structure for the two eyes. Nearly all of these neurons prefer
      orientations between oblique and vertical, and are therefore presumed to be
      involved in processing horizontal disparities. On the other hand, cells that
      prefer orientations near horizontal have matched RF profiles for the two eyes.
      Considered together, these findings suggest that the visual system takes
      advantage of the orientation anisotropy of binocular disparities present in the
      retinal images. 4. For some cells, the spatial structure of the RF changes over
      the time course of the response (inseparable RF in the space-time domain). In
      these cases, the change is similar for the two eyes, and therefore the difference
      remains nearly constant at all times. Because the difference of the RF structure
      between the two eyes is the critical determinant of a cell's relative depth
      selectivity for the proposed model, space-time inseparability of RFs is not an
      obstacle for consistent representation of stereoscopic information. 5. RF
      parameters including amplitude, RF width, and optimal spatial frequency are
      generally well matched for the two eyes over the time course of the response. The
      preferred speed and direction of motion are also well matched for the two eyes.
      These results suggest that the encoding of motion in depth is not likely to be a
      function of simple cells in the striate cortex. 6. The results presented here are
      consistent with our model, in which stereoscopic depth information is encoded via
      differences in the spatial structure of RFs for the two eyes. This model provides
      a natural binocular extension of the current notion of monocular spatial form
      encoding by a population of simple cells. Note, however, that our findings do not
      exclude the possibility that positional shifts of RFs also play a role in
      determining the disparity selectivity of cortical neurons.

PMID- 8734581
TI  - Comparison of discharge variability in vitro and in vivo in cat visual cortex
      neurons.
AB  - 1. In neocortical slices, the majority of neurons fire quite regularly in
      response to constant current injections. But neurons in the intact animal fire
      irregularly in response to constant current injection as well as to visual
      stimuli. 2. To quantify this observation, we developed a new measure of
      variability, which compares only adjacent interspike intervals and is therefore
      less sensitive to rate variations than existing measures such as the coefficient
      of variation of interspike intervals. 3. We find that the variability of firing
      is much higher in cells of primary visual cortex in the anesthetized cat than in
      slice. The response to current injected from an intracellular electrode in vivo
      is also variable, but slightly more regular and less bursty than in response to
      visual stimuli. 4. Using a new technique for analyzing the variability of
      integrate-and-fire neurons, we prove that this behavior is consistent with a
      simple integrate-and-fire model receiving a large amount of synaptic background
      activity, but not with a noisy spiking mechanism.

PMID- 8734582
TI  - Motor patterns for two distinct rhythmic behaviors evoked by excitatory amino
      acid agonists in the Xenopus embryo spinal cord.
AB  - 1. Mechanisms underlying the selective expression of different motor patterns in
      vertebrates are poorly understood. Immobilized, spinal Xenopus embryos are used
      here to examine the motor patterns evoked by various concentrations of excitatory
      amino acids. 2. Relatively low concentrations of N-methyl-D-aspartate (NMDA) (40
      60 microM), kainate (7-8 microM), and alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate (AMPA) (5 microM) evoked motor root discharge characteristic
      of swimming. Brief applications of higher concentrations of kainate (20-40
      microM), AMPA (25-30 microM), quisqualate (5 microM), and glutamate (1-4 mM)
      evoked sequences of a different motor pattern: struggling. This is characterized
      by a longer cycle period, increased burst duration, and a reversed longitudinal
      pattern of motor root discharge. The struggling pattern was never evoked by
      higher concentrations of NMDA (300-500 microM), but was evoked by 30 microM AMPA
      or 5 microM quisqualate in the presence of 50 microM D-2-amino-5
      phosphonopentanoic acid. 3. Intracellular recordings from presumed spinal
      motoneurons showed different patterns of activity during agonist-evoked swimming
      and struggling. The patterns were like those described previously during sensory
      evoked behavior. 4. Caudal applications of excitatory amino acids that produced
      struggling discharge did so only at caudal motor roots, whereas caudal
      applications of NMDA evoked swimming activity throughout the spinal cord. 5.
      During excitatory-amino-acid-evoked struggling, sensory Rohon-Beard neurons
      depolarized up to 7 mV, but did not fire. 6. The results show that expression of
      the struggling pattern, like swimming, is not critically dependent on sensory
      discharge. The results are also consistent with the idea that expression of the
      two very different motor patterns for swimming or struggling in this simple
      vertebrate preparation can be controlled by the level of excitation within the
      spinal motor circuitry, and need not involve the activity of a specific external
      neuromodulator.

PMID- 8734583
TI  - Corticomotoneuronal contribution to the fractionation of muscle activity during
      precision grip in the monkey.
AB  - 1. During independent finger movements, the intrinsic muscles of the hand show a
      fractionated pattern of activity in which the timing and amplitude of
      electromyographic (EMG) activity varies considerably from one muscle to another.
      It has been suggested that, in the macaque monkey, corticomotoneuronal (CM) cells
      that produce postspike facilitation (PSF) of EMG in these muscles contribute to
      this fractionation. To test this hypothesis, we have investigated the
      relationship between the pattern of PSF exerted by a CM cell and the pattern of
      activity shown by the cell and by its target muscles. 2. The activity of 15
      identified CM cells was recorded from two monkeys that performed a precision grip
      task. Spike-triggered averaging of rectified EMG during the hold period of this
      task showed that each cell produced PSF in at least two intrinsic hand muscles.
      3. Segments of data were selected from the initial movement period of the task in
      which the EMG activity in one target muscle was substantially greater than that
      of the other, and the mean firing rate of each CM cell was determined for these
      periods. 4. CM cells showed bursts of activity in the movement period. Most of
      them (13/15) had a significantly (P < 0.001) higher firing rate when one of its
      target muscles was more active than the other. For nine of these cells
      (identified as set A), this muscle was the one receiving the larger PSF. In four
      cases (set B), the reverse was true. Two cells (set C), which produced PSF of
      equal size in their target muscles, showed no change in firing rate across the
      periods of fractionated EMG activity. 5. All set A and set B cells fired at
      significantly (P < 0.001) higher rates during the movement period, in association
      with fractionation of EMG activity, than in the hold period, in which a
      cocontracted pattern of muscle activity was observed. 6. There were pronounced
      differences in the strength of PSF exerted by the CM cells on their target
      muscles during the fractionation periods. One CM cell exerted PSF of a muscle
      during one period of fractionation, but postspike suppression of the same muscle
      during the other period. 7. It is suggested that changes in the firing rate of a
      CM cell and in the degree of facilitation it exerts could both contribute to the
      fractionation of activity in its target muscles. Cells of set A appear to be
      specifically recruited in a manner that directly reflects the pattern of
      facilitation they exert on the sampled target muscles. These results may explain
      why the CM system is so important for the performance of relatively independent
      finger movements.

PMID- 8734584
TI  - Spatial determinants of multisensory integration in cat superior colliculus
      neurons.
AB  - 1. Although a representation of multisensory space is contained in the superior
      colliculus, little is known about the spatial requirements of multisensory
      stimuli that influence the activity of neurons here. Critical to this problem is
      an assessment of the registry of the different receptive fields within individual
      multisensory neurons. The present study was initiated to determine how closely
      the receptive fields of individual multisensory neurons are aligned, the
      physiological role of that alignment, and the possible functional consequences of
      inducing receptive-field misalignment. 2. Individual multisensory neurons in the
      superior colliculus of anesthetized, paralyzed cats were studied with the use of
      standard extracellular recording techniques. The receptive fields of multisensory
      neurons were large, as reported previously, but exhibited a surprisingly high
      degree of spatial coincidence. The average proportion of receptive-field overlap
      was 86% for the population of visual-auditory neurons sampled. 3. Because of this
      high degree of intersensory receptive-field correspondence, combined-modality
      stimuli that were coincident in space tended to fall within the excitatory
      regions of the receptive fields involved. The result was a significantly enhanced
      neuronal response in 88% of the multisensory neurons studied. If stimuli were
      spatially disparate, so that one fell outside its receptive field, either a
      decreased response occurred (56%), or no intersensory effect was apparent (44%).
      4. The normal alignment of the different receptive fields of a multisensory
      neuron could be disrupted by passively displacing the eyes, pinnae, or
      limbs/body. In no case was a shift in location or size observed in a neuron's
      other receptive field(s) to compensate for this displacement. The physiological
      result of receptive-field misalignment was predictable and based on the location
      of the stimuli relative to the new positions of their respective receptive
      fields. Now, for example, one component of a spatially coincident pair of stimuli
      might fall outside its receptive field and inhibit the other's effects. 5. These
      data underscore the dependence of multisensory integrative responses on the
      relationship of the different stimuli to their corresponding receptive fields
      rather than to the spatial relationship of the stimuli to one another.
      Apparently, the alignment of different receptive fields for individual
      multisensory neurons ensures that responses to combinations of stimuli derived
      from the same event are integrated to increase the salience of that event.
      Therefore the maintenance of receptive-field alignment is critical for the
      appropriate integration of converging sensory signals and, ultimately,
      elicitation of adaptive behaviors.

PMID- 8734585
TI  - A voltage-dependent and calcium-permeable ion channel in fused presynaptic
      terminals of Torpedo.
AB  - 1. We used a preparation of fused presynaptic nerve terminals of Torpedo
      electromotor nerve and the patch-clamp technique for characterization of single
      ion channels. We report here of a large, nonselective ion channel which is highly
      voltage dependent. 2. The slope conductance of the I-V relation was estimated by
      either direct measurement of the single-channel current amplitude at different
      voltages (850 +/- 18 pS (SE); n = 9) or by variance analysis (834 +/- 23 pS; n =
      5). 3. The voltage dependence was examined in three ways. At steady-state DC
      voltage conditions, NPo (the open probability times the number of channels in the
      patch) was estimated. At potentials < 0 mV, the probability of the channel to
      open is negligible and increases dramatically, within a very narrow voltage
      range, to > 50% at +8 mV (n = 8). 4. In pulse experiments, the activation time
      delay is shorter as the voltage step reaches more positive values. The mean time
      for half activation (T1/2) decreases from 15 ms at +10 mV to 4 ms at +30 mV (n =
      5). 5. Ensemble currents exhibit rectification in response to voltage ramps at
      negative potentials (n = 10). 6. The channel was found to be nonselective. Its
      permeability to Na+, K+, Cl-, glutamate, Ba+2, and Ca+2, relative to Na+, was
      1.00, 1.00, 1.22, 1.07, 0.85, and 0.62, respectively. 7. Based on the transport
      number of calcium, the calculated driving force, and the mean channel open time,
      we estimated the number of calcium ions entering the nerve terminal upon
      depolarization. This number is not substantially different from the number of
      ions entering through voltage-dependent, calcium-selective channels in other
      cells. 8. We speculate that this nonselective ion channel, may serve as a calcium
      entry route into the nerve terminal and hence be involved in transmitter release.

PMID- 8734586
TI  - Stretch-sensitive afferent neurons in cat knee joint capsule: sensitivity to
      axial and compression stresses and strains.
AB  - 1. Experiments were performed to determine whether the response of stretch
      sensitive mechanoreceptors to tissue deformation is caused by the axial
      stretching of the tissue or by the associated transverse compression of the
      tissue caused by the Poisson effect. 2. Single, stretch-sensitive
      mechanoreceptors were recorded in vitro in a preparation of innervated, isolated
      capsule from the cat knee. Afferents were isolated in a ligamentous capsule
      thickening that has a uniform geometry and parallel collagen fibers. The tissue
      was loaded axially while simultaneously stretching it around the surface of a
      cylinder to produce compression stresses and strains. Axial stresses and strains
      were measured or estimated. 3. By altering the diameter of the cylinder, given
      axial stresses and strains produced different levels of compression stresses and
      strains. It was possible to compare the neuronal response to pure uniaxial
      tension with the response when both axial stretching and transverse compression
      was applied. 4. In 8 of 11 experiments, transverse compression did not
      significantly change the response (P > 0.05). In one experiment, the response was
      decreased by compression. In the other two experiments, the response was
      increased but was not a function of the magnitude of the compressive stress. 5.
      Compressive strain was not significantly correlated with neuron response in any
      experiment. 6. The data do not sustain the model that the responses of stretch
      sensitive neurons are due to local compression of the afferent ending.

PMID- 8734587
TI  - Effect of spike blockade on the receptive-field size of amacrine and ganglion
      cells in the rabbit retina.
AB  - 1. Intracellular recordings were obtained from 21 amacrine cells and 12 ganglion
      cells in the isolated, superfused retina-eyecup of the rabbit. Cells were
      subsequently labeled with horseradish peroxidase (HRP) or N-(2-aminoethyl)
      biotinamide hydrochloride (Neurobiotin) for morphologic identification. 2.
      Initial experiments performed on three amacrine cells and three ganglion cells
      showed that 1 microM tetrodotoxin (TTX) abolished all spiking. This included both
      large-amplitude and small-amplitude spikes recorded in many amacrine cells,
      indicating that they are mediated by voltage-gated sodium channels. 3. The center
      receptive-field size of 18 amacrine cells and 9 ganglion cells was measured with
      the use of a 50-microns-wide/6.0-mm-long rectangular slit of light that was
      displaced along its minor axis (parallel to the visual streak) in steps as small
      as 3 microns. The retina was then bathed in 1 microM TTX, or individual cells
      were injected with 50 mM QX-314, a quatemary lidocaine derivative, to abolish all
      spiking, and the center-receptive field of each cell was then remeasured. 4.
      Although TTX blocked spiking in all ganglion cells (dendritic diameters ranging
      from 302 to 969 microns), it produced no significant change in the size of their
      center-receptive fields. This finding argues that passive, electrotonic spread of
      synaptic inputs to ganglion cell dendritic arbors is adequate for efficient
      propagation from terminal branches to the soma; active propagation via voltage
      gated sodium channels plays no apparent role. 5. In contrast, TTX and QX-314 had
      variable effect on the receptive fields of amacrine cells, which was related to
      the size of their dendritic arbors. Whereas TTX had no significant effect on the
      receptive-field size of amacrine cells whose dendritic arbors were < 525 microns
      across, the center-receptive fields of larger amacrine cells were reduced, on
      average, by 40%; QX-314 produced a very similar average reduction of 39%.
      Moreover, for these larger cells, there was a direct relationship between the
      magnitude of the reduction in receptive-field size produced by TTX or QX-314 and
      the size of a cell's dendritic arbor. This relationship was true whether the
      change in receptive-field size was measured in absolute terms or as percent
      reduction from control values. 6. Interestingly, TTX and QX-314 also
      significantly reduced the amplitude of slow potentials recorded in amacrine cells
      by an average of 22 and 24%, respectively. However, the amplitude of slow
      potentials recorded in ganglion cells were relatively uneffected by TTX. 7. These
      findings are consistent with the idea that, for amacrine cells with dendritic
      arbors spanning > 525 microns, active propagation of synaptic signals mediated by
      voltage-gated sodium channels is necessary for efficient movement of information
      across a cell's dendritic arbor and thus plays a major role in shaping their
      receptive fields. Although the TTX effects may also reflect an indirect
      contribution from altered synaptic input derived from presynaptic spiking
      neurons, the strong similarity between the effects of TTX and QX-314 argues that
      any such contribution was minor. For smaller amacrine cells, passive,
      electrotonic spread of signals appears adequate for efficient propagation within
      their limited dendritic arbors.

PMID- 8734588
TI  - Hyperosmotic regulation of voltage-gated calcium currents in rat anterior
      pituitary cells.
AB  - 1. The sensitivity of voltage-gated calcium currents to hyperosmotic media
      containing mannitol or sucrose (373-723 mOsm) and to the dihydropyridine (DHP)
      calcium channel agonist Bay K 8644 was examined in enriched populations of rat
      anterior pituitary somatotrophs by using the whole cell mode of the patch-clamp
      technique. 2. Hyperosmotic media reduced the amplitude of voltage-gated calcium
      currents. With a 61.9% increase in extracellular medium osmolarity (523 mOsm),
      low voltage-activated (LVA) calcium currents were reduced to 67.9 +/- 17.8% of
      control size and high voltage-activated (HVA) calcium currents were reduced to
      57.0 +/- 5.7% (mean +/- SD) of control size. The hyperosmotic suppression of HVA
      calcium currents was usually accompanied with a negative shift of 6.0 +/- 2.9 mV
      (mean +/- SD) in the activation curve of HVA currents. 3. The DHP calcium-channel
      agonist Bay K 8644 (10 microM), which stimulates hormone secretion from
      somatotrophs, increased the amplitude of HVA calcium currents to 212.6 +/- 67.2%
      of their control size, prolonged their tail currents, and negatively shifted the
      activation curve of HVA calcium currents by 6.2 +/- 2.8 mV. 4. Hyperosmotic media
      reduced the amplitude of DHP-sensitive HVA calcium currents and their associated
      prolonged tail currents, thus providing direct evidence for hyperosmotic
      suppression of DHP-sensitive currents. 5. Hence, exposure of pituitary cells to
      hyperosmotic media reduced voltage-sensitive calcium influx through LVA and DHP
      sensitive HVA calcium channels. The inhibition of calcium influx through DHP
      sensitive channels, which are implicated in regulation of hormone secretion in
      these cells, suggests that inhibitory hyperosmotic effects on hormone secretion
      from pituitary cells may stem from inhibition of calcium influx, before the
      exocytotic process. These results may also be relevant to effects of
      hypertonicity on neurosecretion in the nervous system.

PMID- 8734589
TI  - Decrement of GABAA receptor-mediated inhibitory postsynaptic currents in dentate
      granule cells in epileptic hippocampus.
AB  - 1. Inhibitory postsynaptic currents (IPSCs) were studied in hippocampal dentate
      granule cells (DGCs) in the pilocarpine model and human temporal lobe epilepsy,
      with the use of the whole cell patch-clamp recording technique in slice
      preparations. 2. In the pilocarpine model, hippocampal slices were prepared from
      rats that were allowed to experience spontaneous seizures for 2 mo. Human
      hippocampal specimens were obtained from epileptic patients who underwent
      surgical treatment for medically intractable seizures. 3. IPSCs were generated by
      single perforant path stimulation and recorded at a membrane potential (Vm) of 0
      mV near the reversal potential of glutamate excitatory postsynaptic currents in
      the voltage-clamp recording. IPSCs were pharmacologically identified as gamma
      aminobutyric acid-A (GABAA) IPSCs by 10 microM bicuculline methiodide. 4. During
      low-frequency stimulation, IPSCs were not different in amplitude among non
      seizure-experienced rat hippocampi, human nonsclerotic hippocampi, seizure
      experienced rat hippocampi, and human sclerotic hippocampi. In the last two
      groups of DGCs, current-clamp recordings indicated the presence of prolonged
      excitatory postsynaptic potentials (EPSPs) mediated by the N-methyl-D-aspartate
      (NMDA) receptor. 5. High-frequency stimulation, administered at Vm = -30 mV to
      activate NMDA currents, reduced GABAA IPSC amplitude specifically in seizure
      experienced rat hippocampi (t = 2.5, P < 0.03) and human sclerotic hippocampi (t
      = 7.7, P < 0.01). This reduction was blocked by an NMDA receptor antagonist, 2
      amino-5-phosphonovaleric acid (APV) (50 microM). The time for GABAA IPSCs to
      recover to their original amplitude was also shortened by the application of APV.
      6. I conclude that, when intensively activated, NMDA receptor-mediated excitatory
      transmission may interact with GABAergic synaptic inhibition in DGCs in seizure
      experienced hippocampus to transiently reduce GABA(A) receptor-channel function.
      Such interactions may contribute to give rise to epileptic excitation in
      chronically seizure-prone hippocampus.

PMID- 8734590
TI  - Glutamate-induced long-term potentiation enhances spontaneous EPSC amplitude but
      not frequency.
AB  - 1. Many examples of long-term potentiation (LPT) are induced by repetitive
      electrical stimulation of presynaptic axons. LTP also is induced by direct
      glutamate iontophoresis (1 M, 1-2 microA, 10 s) onto postsynaptic neurons in
      hippocampal slices without evoked presynaptic stimulation; this form of LTP is
      called "ionto-LTP". The studies herein test the hypothesis that ionto-LTP is
      expressed primarily through postsynaptic mechanisms. 2. Whole cell recordings
      were used to examine the amplitude and frequency of spontaneous excitatory
      postsynaptic currents (sEPSCs) in CA1 pyramidal neurons. sEPSCs were composed of
      an equal mixture of tetrodotoxin (TTX)-insensitive miniature EPSCs and EPSCs that
      appeared to result from spontaneous action potentials (i.e., TTX-sensitive
      EPSCs). The detection of all sEPSCs was virtually eliminated by 6-cyano-7
      nitroquinoxaline-2,3-dione (20 microM), suggesting that sEPSCs were glutamate
      mediated synaptic events. 3. Changes in the amplitude and frequency of sEPSCs
      were examined during the expression of ionto-LTP to obtain new information about
      the cellular location of mechanisms involved in synaptic plasticity. Our findings
      show that ionto-LTP expression results in increased sEPSC amplitude in the
      absence of lasting increases in sEPSC frequency. 4. Potentiation of sEPSC
      amplitude without changes in sEPSC frequency has been previously interpreted to
      be due to postsynaptic mechanisms. Although this interpretation is supported by
      findings from peripheral synapses, its application to the central nervous system
      is unclear. We have considered alternative mechanisms. Models based on increased
      release probability for action potential dependent transmitter release appeared
      insufficient to explain our results. The most straightforward interpretation of
      our results is that LTP induced by glutamate iontophoresis on dendrites of CA1
      pyramidal neurons is mediated largely by postsynaptic changes.

PMID- 8734591
TI  - Single-domain/bound calcium hypothesis of transmitter release and facilitation.
AB  - 1. We describe a model of transmitter release that is based on the finding that
      release can be gated during the opening of individual Ca2+ channels, suggesting
      that the release site can be activated by the Ca2+ domain under a single channel.
      In this model each release site contains four independent Ca2+ binding sites or
      gates with unbinding kinetics graded from slow to fast and affinities ranging
      from high to low. All four gates must be bound for release to occur. Thus
      synaptic dynamics are governed by the kinetics of Ca2+ binding and unbinding from
      release sites, not Ca2+ diffusion. 2. Fast facilitation occurs when an action
      potential invades a terminal with one or more ions remaining bound to the release
      sites. Residual free Ca2+ is not necessary for facilitation with this mechanism,
      but if present it would enhance facilitation by binding to high-affinity gates
      between pulses. 3. This model can account for key features of release. These
      include fourth-power cooperativity with regard to external Ca2+; a release time
      course that is virtually independent of an increase in quantal content; an
      inverse relation between external Ca2+ and the degree of facilitation; and a
      steplike increase in facilitation with increasing stimulus frequency, with each
      step corresponding to a unitary decline in the Ca2+ cooperativity. 4.
      Facilitation of single-channel-based secretion is shown to be robust even if
      channel opening is stochastic. Spontaneous release of transmitter, assumed to be
      due in part to spontaneous Ca2+ channel openings, is shown to be elevated during
      and after a train of impulses. 5. An extension of the model to include multiple
      Ca2+ channels per release site demonstrates that one role of overlapping Ca2+
      domains may be to accentuate depolarization-evoked release relative to
      spontaneous release.

PMID- 8734592
TI  - Transient and sustained depolarization of retinal ganglion cells by Ih.
AB  - 1. Using whole cell patch-clamp methods, we have identified an inward cationic
      current activated by hyperpolarization (Ih) in somata of goldfish retinal
      ganglion cells. 2. Ih activated at test potentials between -70 and -105 mV, and
      did not appear to inactivate during prolonged hyperpolarizations under voltage
      clamp. During step hyperpolarizations from holding potentials between -70 and -40
      mV, apparent activation was faster at more negative test potentials. On
      repolarization from -105 mV to holding potentials between -75 and -55 mV, Ih
      deactivated exponentially at rates showing no marked voltage dependence (tau =
      approximately 100 ms). 3. Ih tail currents reversed at membrane potentials
      consistent with a relative permeability to Na+ and K+ of roughly 0.5, when
      pipette and bath solutions both contained Na+ and K+. 4. Ih was readily blocked
      by extracellular Cs+ (3 mM), but was resistant to block by tetraethylammonium (30
      mM), Ba2+ (1 mM), or Co2+ (2.4 mM). 5. Time-dependent voltage rectification
      developed during injection of hyperpolarizing current under current clamp. After
      current injection ceased, membrane potential depolarized beyond resting
      potential, often leading to anode-break-like spikes. Both voltage rectification
      and voltage overshoot were suppressed by extracellular Cs+. 6. Voltage-clamp
      measurements in the presence and absence of Cs+ were used to model membrane
      potential changes produced by exogenous current injections, by hyperpolarizing
      synaptic inputs, and by termination of both. Modeled responses resembled membrane
      potential changes measured under current clamp when terms for activation and
      deactivation of Ih were included. 7. The voltage rectification and anode-break
      like spikes observed in isolated cells resemble those recorded during and after
      light-evoked hyperpolarizations of retinal ganglion cells in situ. Ih may
      transiently augment retinal ganglion cell excitability after termination of
      hyperpolarizing light stimuli, and thus promote encoding of stimulus timing.

PMID- 8734593
TI  - Membrane properties and cell ultrastructure of taste receptor cells in Necturus
      lingual slices.
AB  - 1. Whole cell patch-clamp recordings and electron micrographs were obtained from
      cells in Necturus taste buds in lingual slices to study their membrane properties
      and to correlate these properties with cell ultrastructure. 2. Two different
      populations of taste receptor cells could be identified: one type possessed
      voltage-gated Na+ and K+ (noninactivating) currents (group 1 cells); the other
      type possessed only K+ (inactivating) currents (group 2 cells). 3. The zero
      current ("resting") potential (Vo) and whole cell resistance (Ro) of these two
      types of taste cells differed significantly. For group 1 cells, on average, Vo = 
      75 mV and Ro = 24.6 G omega, and for group 2 cells, Vo = -49 mV and Ro = 48.9 G
      omega. The difference in Ro was not explained completely by differences in cell
      sizes, suggesting that intrinsic membrane properties differed between the
      populations. 4. Cells injected with biocytin were the electron microscope after
      tissues were reacted with majority (14 of 16) of cells with voltage-gated Na+ and
      K+ currents (group 1 cells) were characterized by abundant rough endoplasmic
      reticulum and dense granular packets in the apical process. These are features of
      dark cells. All the cells that only possessed K+ currents (group 2 cells) were
      characterize by well-developed smooth endoplasmic reticulum and an absence
      granular packets. These features characterize light cells. 5. These findings
      indicate that there is a good, although not exact, correlation between
      electrophysiological properties and cell morphotype in Necturus taste bud cells.
      All dark cells possessed Na+ and K+ currents and thus would be expected to be
      capable of generating action potentials. Most light cells only possessed outward
      K+ currents and thus would be incapable of generating action potentials.

PMID- 8734594
TI  - Subjective scaling of smooth surface friction.
AB  - 1. Six men and four women, 30-51 yr of age, were asked to use the tip of the
      washed and dried index finger to stroke six different featureless, flat surfaces
      mounted on a three-dimensional force platform. The six surfaces were rosin-coated
      glass, glass, satin-finished aluminum, poly-vinyl chloride (PVC) plastic, Teflon,
      and nyloprint (polyamide plastic). The subjects were requested to indicate where
      the sensation produced by each surface should be placed on an unidimensional
      scale represented by an 18cm line labeled at one end by the words "most slippery"
      and at the other end by the words "most sticky." The coefficients of friction for
      each surface and for each subject were subsequently assessed by asking each
      subject to stroke the surfaces as if they were assessing its slipperiness for 5
      s. 2. The finger forces normal and tangential to the stroked surfaces were
      digitized at 250 Hz and stored on a laboratory computer. The ratio of the mean
      tangential force to the mean perpendicular force during stroking was used to
      calculate the mean coefficient of kinetic friction. The mean friction for all
      subjects ranged from 0.43 for the nyloprint surface to 2.79 for the rosin-coated
      glass. Correlation coefficients calculated between the subjective estimates of
      friction and the measured coefficients of friction for each subject individually
      resulted in a mean correlation of 0.85 (n = 10, P < 0.001). 3. These data
      indicate that subjects can accurately scale relative differences in the friction
      of macroscopically smooth, flat surfaces, by modulating the tangential force
      applied to the finger while keeping the normal force relatively constant. The
      fact that subjects maintained a relatively constant normal force and instead
      varied the tangential force across different surfaces suggests that receptors
      sensitive to these tangential forces are important in the perception of smooth
      surface friction.

PMID- 8734595
TI  - Friction, not texture, dictates grip forces used during object manipulation.
AB  - 1. Three men and seven women, 25-40 yr of age, were asked to use the thumb and
      index fingers to grasp, lift, and hold the armature of a linear motor generating
      a 2.0-N opposing force (simulating an object weighing approximately 200 g) for 2
      s. The surface in contact with the fingers was composed of smooth or polyamide
      plastic etched with 1.0-mm high Braille beads separated at 2.0- or 3.0-mm
      intervals measured from apex to apex. The surfaces were left either untreated or
      coated with talc, water, or sucrose films designed to change the coefficient of
      friction with the skin. Talc reduced the coefficient of friction, whereas water
      and sucrose both increased the friction against the skin. In all, 12 surface
      conditions were used to evaluate the effects of texture and friction on the grip
      force during lifting and holding. 2. For all subjects the inverse coefficient of
      friction was associated with proportionately scaled increases in grip force,
      regardless of surface texture. The peak lifting force as well as the static force
      used to hold the object stationary were significantly correlated with the inverse
      of the coefficient of friction. When coatings were applied to dissimilar surface
      textures to produce similar coefficients of friction, the grip force profiles
      were nearly identical. When strong adhesives increased the friction of the smooth
      surface compared with textured surfaces, grip forces decreased as friction
      increased. That is, although the untreated smooth surface had less friction than
      either of the two textured surfaces, the addition of sucrose increased the smooth
      surface friction to a higher level than either of the similarly treated textured
      surfaces. As a result, the effect of surface friction could be dissociated from
      the effect of either surface texture or coating. Friction appears to be a more
      important factor in determining the grip force than either texture or surface
      films at least for the range of textures and coatings examined in this study.

PMID- 8734596
TI  - Orbitofrontal cortex neurons: role in olfactory and visual association learning.
AB  - 1. The orbitofrontal cortex is implicated in the rapid learning of new
      associations between visual stimuli and primary reinforcers such as taste. It is
      also the site of convergence of information from olfactory, gustatory, and visual
      modalities. To investigate the neuronal mechanisms underlying the formation of
      odor-taste associations, we made recordings from olfactory neurons in the
      orbitofrontal cortex during the performance of an olfactory discrimination task
      and its reversal in macaques. 2. It was found that 68% of odor-responsive neurons
      modified their responses after the changes in the taste reward associations of
      the odorants. Full reversal of the neuronal responses was seen in 25% of these
      neurons. Extinction of the differential neuronal responses after task reversal
      was seen in 43% of these neurons. 3. For comparison, visually responsive
      orbitofrontal neurons were tested during reversal of a visual discrimination
      task. Seventy-one percent of these visual cells showed rapid full reversal of the
      visual stimulus to which they responded, when the association of the visual with
      taste was reversed in the reversal task. 4. These demonstrate that of many
      orbitofrontal cortex olfactory neurons on the taste with which the odor is
      associated. 5. This modification is likely to be important for setting the
      motivational value of olfactory for feeding and other rewarded behavior. However,
      it is less complete, and much slower, than the modifications found or orbit
      frontal visual during visual-taste reversal. This relative inflexibility of
      olfactory responses is consistent with the need for some stability is odor-taste
      associations to facilitate the formation and perception of flavors.

PMID- 8734597
TI  - Representation of olfactory information in the primate orbitofrontal cortex.
AB  - 1. To analyze the information represented about individual odor stimuli in the
      responses of single olfactory neurons in the primate orbitofrontal area, neuronal
      responses were measured to a set of seven to nine odorants in macaques performing
      an olfactory discrimination task. The population of neurons analyzed had
      responses that were significantly differential to the odorants. 2. Information
      theoretic analyses were applied to the responses of the neurons, and information
      measures were calculated from the firing rate of the responses and from the
      principal components of the responses. The information reflected by the firing
      rate of the response accounted for the majority of the information present (86%)
      when compared with the information derived from the first three principal
      components of the spike train. This indicated that temporal encoding had a very
      minor role in the encoding of olfactory information by single orbitofrontal
      olfactory cells. 3. The average information about which odorant was presented,
      averaged across the 38 neurons, was 0.09 bits, a figure that is low when compared
      with the information values previously published for the responses of temporal
      lobe face-selective neurons. 4. Application of information theoretic analyses to
      the responses of these neurons showed how much information about which stimulus
      was delivered was present in the responses of individual neurons. It was found
      that for the majority of the neurons significant amounts of information were
      reflected about one or two of the odorants presented. 5. For each neuron, the
      information reflected in the responses of that neuron about the reinforcement
      value and the information about the identity of the odorants were calculated. It
      is shown that many neurons carry information about which of the odorants was
      presented; in addition, some neurons reflect information only about the taste
      association of the stimuli and not about odorant identity. 6. Measurements of the
      sparseness of the representation indicated that a broadly distributed
      representation of the identity of odorants was present in this population of
      neurons.

PMID- 8734598
TI  - Recruitment of triceps surae motor units in the decerebrate cat. I. Independence
      of type S units in soleus and medial gastrocnemius muscles.
AB  - 1. We tested the hypothesis that reflex inhibition of soleus motor units reflects
      selective inhibition of slow-twitch (type S) motor units throughout the triceps
      surae. Physiological properties including type, together with firing behavior,
      were measured from single motor units in the medial gastrocnemius (MG) muscle of
      decerebrate cats with the use of intra-axonal recording and stimulation. MG unit
      firing was contrasted during net inhibition or excitation of the slow-twitch
      soleus muscle produced by ramp-hold-release stretches of MG. 2. Stretch of the MG
      muscle increased the firing of type S motor units in the MG regardless of the
      reflex response of the soleus muscle. When stretch inhibited soleus, each of the
      14 type S units sampled from MG either was newly recruited or exhibited increases
      in the rate of ongoing firing. Increased firing was observed in 320 of 321
      stretch trials. For 8 of these 14 units, a total of 155 stretch trials evoked
      reflex excitation of soleus, and unit firing increased in all trials. 3. For the
      eight MG type S motor units studied during both reflex inhibition and excitation
      of soleus, firing rate tended to be higher during inhibition. The higher rates
      were also associated with the higher MG forces required to elicit soleus
      inhibition. For one MG type S unit it was possible to compare firing rates during
      soleus inhibition and excitation for trials of overlapping levels of MG force.
      For this unit, firing rate was similar, but still appreciably higher, during
      inhibition. 4. Soleus inhibition was also produced by stretch of the plantaris
      (PL) or lateral gastrocnemius (LG) muscles. Type S units in PL (n = 2) or in LG
      (n = 1) were recruited or increased firing rate even when stretch of these
      muscles produced soleus inhibition. 5. The firing behavior of 12 fast-twitch
      (type F) units was studied (11 from MG, 1 from PL). All type F units either were
      recruited or accelerated the rate of firing during soleus inhibition, as well as
      during soleus excitation. 6. These findings give evidence that reflex inhibition
      of type S motor units in the soleus muscle does not necessarily reflect an
      organizational scheme in which there is inactivation of type S units in other
      active muscles. In the DISCUSSION we point out the absence of direct evidence for
      selective inactivation of units on the basis of their type classification.

PMID- 8734599
TI  - Recruitment of triceps surae motor units in the decerebrate cat. II.
      Heterogeneity among soleus motor units.
AB  - 1. On the basis of the orderly activation of motoneurons in a pool, one would
      predict that motor unit activity and whole muscle force will change at least
      roughly in parallel: active motor units should continue to fire as net muscle
      force increases and quiescent motor units should remain inactive as muscle force
      decreases. We have consistently observed this relationship in our studies of the
      medial gastrocnemius (MG) muscle, but here we report an uncoupling of the soleus
      muscle and some of its motor units. 2. Physiological properties and firing
      behaviors of 20 soleus motor units were characterized in five decerebrate cats
      with the use of intra-axonal stimulation and recording. Motor unit firing was
      elicited in reflexes initiated by muscle stretch, nerve stimulation, and
      mechanical stimulation of the heel. Particular emphasis was placed on the
      heterogenic reflexes produced in soleus by ramphold-release stretches of the MG
      muscle. In agreement with previous reports, either net heterogenic excitation or
      inhibition of the soleus muscle was produced in separate trials of MG stretch. 3.
      During excitation of soleus in autogenic stretch reflexes and in crossed
      extension reflexes, all 20 units were recruited or increased firing, i.e., unit
      firing was coupled with soleus force. In the other reflexes, however, unit firing
      and muscle force were uncoupled for 10 of these units. Six tonically active motor
      units were inhibited during an increase in soleus force produced by MG stretch or
      by mechanical stimulation of the heel. Four motor units were activated during a
      decrease in soleus force produced by the same stimuli. 4. Six motor units were
      studied during both soleus inhibition and excitation evoked by MG stretches. One
      motor unit was consistently coupled to the soleus muscle response; firing
      increased during soleus excitation and decreased during inhibition. However, four
      soleus motor units were inhibited under both conditions, and one unit was excited
      under both conditions. Thus the firing behavior of five of these six motor units
      was the same in response to MG stretch, irrespective of the soleus response. 5.
      The uncoupling was most clearly recognized when tonically active units ceased
      firing during net excitation of the soleus muscle and when silent units began
      firing during net inhibition of the soleus muscle. Unit responses were not as
      striking in all trials of MG stretch (spike number increased or decreased
      relative to prestretch values by 1-4 spikes), but the responses were consistent
      across trials; in multiple stretches, spike number commonly either increased or
      decreased. Intertrial regularity was also observed in units for which firing was
      coupled with the net reflex response of the soleus muscle. 6. Divergence in the
      firing of soleus motor units was also observed in three cases in which records
      were taken simultaneously from two motor units. In one pair, one unit increased
      and the other decreased firing during MG stretch-evoked inhibition of soleus. In
      the other two pairs, one unit increased and the other decreased firing when
      soleus was excited by heel stimulation. In all pairs, the unit that decreased
      firing under these conditions had the lowest recruitment threshold in response to
      the soleus stretch. 7. Although all soleus motor units were classified as slow
      twitch (type S), variation in their physiological properties bore some relation
      to firing behavior. Those units recruited during periods of soleus inhibition
      exhibited among the fastest conduction velocities and contraction times in our
      sample. In all three unit pairs sampled, the unit expressing decreases in firing
      had the slower conduction velocity and contraction time. 8. These findings
      demonstrate that soleus motor units are differentially activated and deactivated
      by peripheral afferents. (ABSTRACT TRUNCATED)

PMID- 8734600
TI  - Presynaptic inhibition of calcium-dependent and -independent release elicited
      with ionomycin, gadolinium, and alpha-latrotoxin in the hippocampus.
AB  - 1. Presynaptic inhibition of synaptic transmission in the hippocampus was
      investigated by comparing the effects of several agonists on miniature excitatory
      and inhibitory postsynaptic currents (mEPSCs and mIPSCs). 2. The Ca2+ ionophore
      ionomycin increased the frequency of mEPSCs and mIPSCs but did not affect their
      amplitude. Ionomycin-induced release required extracellular Ca2+ and was
      prevented by pretreatment with botulinum neurotoxin serotype F, like evoked
      synaptic transmission. Unlike evoked transmission, however, this increase did not
      involve activation of voltage-dependent Ca2+ channels because it was insensitive
      to Cd2+. 3. Both the lanthanide gadolinium and alpha-latrotoxin produced
      increases in the frequency of mEPSCs and mIPSCs, but their actions were
      independent of extracellular Ca2+. 4. Adenosine, the gamma-aminobutyric acid-B
      (GABAB) receptor agonist baclofen, and a mu-opioid receptor agonist strongly
      reduced the frequency of synaptic currents triggered by all three secretagogues.
      5. We conclude that activation of these presynaptic receptors can reduce high
      frequencies of vesicular glutamate and GABA release by directly impairing
      transmitter exocytosis. Presynaptic inhibition of gadolinium- and alpha
      latrotoxin-induced release indicates that this impairment occurs without changes
      in intraterminal Ca2+ homeostasis and when vesicle fusion is rendered Ca2+
      independent, respectively. 6. The inhibition of ionomycin-induced release
      provides additional evidence for a direct, neurotransmitter receptor-mediated
      modulation of the proteins underlying vesicular docking or fusion as an important
      component of presynaptic inhibition of evoked synaptic transmission.

PMID- 8734601
TI  - Dendritic arbor of locus coeruleus neurons contributes to opioid inhibition.
AB  - 1. The nucleus locus coeruleus (LC) is made up of noradrenergic cells all of
      which are hyperpolarized by opioids. Recent work has shown that the reversal
      potential of the opioid-induced current is more negative than the potassium
      equilibrium potential. The aim of the present study was to determine whether the
      extent of the dendritic field could contribute to the very negative opioid
      reversal potential. 2. Individual LC cells were labeled in the brain slice
      preparation. The number of dendrites found on cells in slices sectioned in the
      horizontal plane was greater than cells in coronal slices. However, the
      dimensions of the cell body slices from each plane were not significantly
      different. 3. The resting conductance of neurons from slices cut in the
      horizontal plane was significantly larger than in cells from coronal plane. 4.
      The amplitude of the outward current induced by [Met5]-enkephalin (ME) was larger
      in cells from horizontal slices and the reversal potential was more negative than
      that of cells in coronal slices. 5. The results show that the plane of section
      influences the membrane properties and opioid actions of LC neurons in vitro and
      suggest that these differences correlate with the numbers of dendrites. The
      results suggest that in vivo, in addition to intrinsic membrane properties and
      synaptic inputs, the structural makeup of the nucleus is an important factor in
      determining the activity.

PMID- 8734602
TI  - Relation of chemical structure to spatial distribution of sensory responses in
      rat olfactory epithelium.
AB  - 1. Electroolfactogram (EOG) recordings were made in three configurations from the
      rat olfactory epithelium. Each configuration compared recordings in the
      dorsomedial recess of the epithelium with recordings in ventral or lateral parts
      of the epithelium. Most comparisons were made with simultaneous recordings. The
      exception was a series in which the dorsal recess and lateral space between the
      base of two turbinate bones were directly exposed for odor application and
      recording. The spatial distributions of maximal responses were largely
      independent of recording configuration. 2. Simultaneous recordings compared
      dorsomedial and lateral sites in the epithelium during stimulation with a series
      of 50 odorants. The odorants that evoked larger responses in the lateral sites
      were usually compounds that lacked oxygen containing functional groups (such as
      the carbonyl group). This was true for straight chain and cyclic alkanes, for
      terpine compounds, and for aromatic compounds. The major exception was cineole, a
      bicyclic compound. All compounds containing ketone groups evoked larger
      dorsomedial responses. The responses of aldehydes and esters depended upon
      whether they were attached to aliphatic or aromatic chains. 3. In the three types
      of preparation, the sites responding best to ketones were in the same expression
      zone of the epithelium according to published maps for the rat and mouse. The
      sites responding best to odors without functional groups were in the far lateral
      or ventral region and corresponded to one of the two most lateral and ventral
      expression zones. This fact suggests that the receptors in these regions have a
      preference for particular chemical properties. This level of analysis cannot
      determine whether all receptors in each zone have a stronger response to certain
      properties of these odorants or whether each zone contains different proportions
      of receptors with these properties.

PMID- 8734603
TI  - Mechanical actions of heterogenic reflexes among ankle stabilizers and their
      interactions with plantarflexors of the cat hindlimb.
AB  - 1. The stretch-evoked reflex organization of muscles whose major action is to
      abduct [peroneus brevis (PB); peroneus longus (PL)] and adduct [tibialis
      posterior (TP); flexor digitorum longus (FDL); flexor hallucis longus (FHL)] the
      ankle, and their interactions with the hindlimb extensors gastrocnemius (G) and
      soleus (S), were studied in 27 unanesthetized decerebrate cats. Ramp-hold-release
      stretches of physiological amplitudes were applied to muscle tendons detached
      from their bony insertion, and muscle force output was measured in response to
      these perturbations. Flexion and crossed-extension reflexes were used to modulate
      baseline force. 2. PB and TP shared strong, length-dependent, short-latency
      inhibitory reflexes prominent when the muscles were either actively generating
      force or quiescent. The mechanical characteristics of this reflex suggest Ia
      reciprocal inhibition as the underlying mechanism. Just as reciprocal inhibition
      between S and tibialis anterior stiffens the ankle joint against sagittal
      perturbations, we propose that reciprocal inhibition between PB and TP stiffens
      the ankle joint against nonsagittal perturbations. 3. In all preparations (n = 7)
      and under all conditions examined, PB and PL shared well-demonstrated mutual
      excitation. The reflex responses were asymmetric (favoring excitation of PL),
      length dependent, and occurred simultaneously with the stretch reflex at a
      latency of 16-18 ms. Mutual monosynaptic projections previously described between
      these two muscles explain all of the above findings. Our data further demonstrate
      that, under certain conditions, the ensemble activity of this reflex interaction
      has a powerful effect on the mechanical behavior of the muscle. 4. The
      heterogenic reflex organization of the ankle adductors was as follows: FDL evoked
      a modest excitation on TP, whereas FHL evoked weak inhibition. Latency of the
      excitation from FDL onto TP (24 ms) was greater than expected if the reflex were
      mediated by heteronymous Ia afferents. In all preparations examined (n = 3), TP
      contributed no significant reflexes onto either FDL or FHL. 5. Mutual, asymmetric
      inhibition characterized interactions between PB and the plantarflexors S and G.
      Most remarkable was a novel, long-latency (72-74 ms) reflex inhibition evoked on
      both S and G by stretch of PB. When this inhibition occurred, it dramatically
      decreased the S (or G) stretch response. Longer PB lengths evoked greater
      inhibition of isometric S; regression analysis indicated that the model best
      predicting this inhibition contained muscle force and stiffness terms. No long
      latency reflexes were noted from either G or S onto PB. The mechanism underlying
      long-latency inhibition is presently unknown; however, features of this
      interaction suggest interneurons receive either group II or group III afferent
      input. 6. G and TP shared short latency, mutually inhibitory, asymmetric reflexes
      favoring inhibition of TP. No long-latency interactions were noted, nor were
      there any mechanically significant interactions between S and TP. 7. Reflex
      interactions across the abduction/adduction axis thus favored inhibition of
      plantarflexion and adduction torques while emphasizing abduction torques: PB/S
      (or PB/G) interactions were mutual, asymmetric, and favored inhibition of G and
      S; TP/G interactions were mutual, asymmetric, and favored inhibition of TP; TP/PB
      interactions were approximately balanced. The overall mechanical outcome of these
      inhibitory interactions may partly underlie the global corrective strategy seen
      in intact cats subjected to linear perturbations. 8. No significant reflex
      interactions were demonstrated between PL and TP, G, or S, nor were any long
      latency reflexes noted. Thus, whereas reflex interactions between the
      stereotypically activated PB and other stereotypically activated muscles
      (including TP, G, and S) were strong and well-demonstrated, interactions between
      the variably activated PL and these same muscles were far weaker.

PMID- 8734604
TI  - GABA-induced inactivation of functionally characterized sites in cat visual
      cortex (area 18): effects on direction selectivity.
AB  - 1. Microiontophoresis of gamma-aminobutyric acid was used to reversibly
      inactivate small sites of defined orientation and direction specificity at a
      horizontal distance of 400-700 microns from single cells recorded in cat area 18.
      There was extensive or complete overlap between the receptive fields of cells at
      the recording and inactivation sites. A cell's directionality index [DI: 1 -
      (response to nonpreferred direction/response to preferred direction)], the
      response to the preferred direction, and orientation tuning width (measured at
      half the maximum response) were compared before and during inactivation of either
      iso-orientation sites (where the orientation preference was within 22.5 degrees)
      or cross-orientation sites (where it differed by 45-90 degrees). 2. During iso
      orientation inactivation, 40 (73%) of 55 cells showed a significant (> 0.20)
      change in DI; the mean change in DI for these cells was 0.59. An additional cell
      showed a marked increase in response to the preferred direction that did not
      result in a change in DI. With one exception, the effects occurred in the absence
      of a significant (> 25%) change in orientation tuning width. 3. In most cases,
      the results were broadly predictable in the sense that iso-orientation
      inactivation predominantly affected a cell's response to the direction of motion
      of an optimally oriented bar that was closest to the preferred direction at the
      inactivation site: viz., a decrease in response to the preferred direction and an
      increase in response to the preferred or nonpreferred direction. 4. It is argued
      that the decreases in response were due to a reduction in the strength of
      intracortical iso-orientation excitatory connections made primarily between cells
      with similar direction preferences, whereas the increases in response involved a
      loss of iso-orientation inhibition. 5. In cases where remote inactivation caused
      an increase in response to the nonpreferred direction, comparable effects could
      be elicited when a mask left exposed only the excitatory subregion of the
      receptive field in S cells or the most responsive part of the excitatory
      discharge region in C cells. This implies extensive or complete spatial overlap
      between the profiles of excitation and inhibition in a cell's nonpreferred
      direction. 6. During cross-orientation inactivation, a significant change in DI
      was seen in only 14 (19%) of 73 cells and, with one exception, these changes were
      accompanied by increases in response to non-optimal orientations and significant
      broadening of orientation tuning. The effects of cross-orientation inactivation
      on directionality were presumably due to the loss of cross-orientation
      inhibition, which contributes primarily to orientation tuning. 7. Inactivation of
      the same site could cause an increase in response to the nonpreferred direction
      in cells recorded at iso-orientation sites and an increase in response to
      nonoptimal orientations and broadening of orientation tuning in cells recorded at
      cross-orientation sites. This is consistent with the notion that a single
      inhibitory neuron can contribute to the directionality or orientation tuning of
      different target cells depending on their location in the orientation map. 8. The
      results provide evidence for a major contribution of intrinsic mechanisms to the
      orientation tuning and direction selectivity of cells in cat area 18. It is
      proposed that two different intracortical processes are involved in the
      enhancement of orientation and direction selectivity: 1) suppression of responses
      to nonoptimal orientations and directions as a result of cross-orientation
      inhibition and iso-orientation inhibition; and 2) facilitation of responses to
      optimal orientations/directions via iso-orientation excitatory connections.

PMID- 8734605
TI  - Block of glutamate decarboxylase decreases GABAergic inhibition at the crayfish
      synapses: possible role of presynaptic metabotropic mechanisms.
AB  - 1. The cytosolic concentration of a neurotransmitter is believed to be an
      important factor determining its release. The effects of 3-mercaptopropionic acid
      (MP) and aminooxyacetic acid (AOAA), glutamate decarboxylase (GAD) blockers, on
      GABAergic postsynaptic and presynaptic inhibitory neurotransmission were examined
      in the crayfish (Procambarus clarkii) opener neuromuscular synapses. 2.
      Intracellular recordings of evoked excitatory postsynaptic potentials (EPSPs) and
      inhibitory postsynaptic potentials (IPSPs) as well as loose macropatch clamp
      measurements of excitatory postsynaptic currents (EPSCs) and inhibitory
      postsynaptic currents (IPSCs) were used to evaluate the effects of the drugs,
      which were applied exclusively to the nerve bundle. 3. Under normal conditions, a
      stimulus train to the inhibitor preceding the excitor stimulation elicited a
      large reduction in EPSP amplitude in a time interval-dependent manner. This
      inhibition is effected by postsynaptic as well as presynaptic processes. 4.
      Treatment with MP or AOAA decreased the IPSP amplitude and its altered
      conductance but had no effect on the IPSP reversal potential or the resting
      potential of the cell. They did, however, slightly increase the Rin of the fiber.
      5. Quantal analysis of single IPSCs revealed that GAD blockers increased the
      number of failures and thus reduced quantal content (m), diminished the
      probability of release (p), but did not affect the quantum current (q) or the
      statistical parameter (n), believed to be the number of available active zones.
      6. Quantal analysis of EPSCs, released after interaction with the inhibitor,
      revealed a reduction in m without any effect on q. GAD blockers greatly reduced
      the efficacy of this inhibition without affecting the EPSC q. 7. GAD blockers
      increased the output of the excitor release sites by the following mechanisms: 1)
      increased EPSC, 2) increased EPSC facilitation, or 3) enhancement of spontaneous
      activity (miniature EPSCs). 8. Short time incubation with picrotoxin and CGP
      35348 eliminated IPSCs and evoked inhibition. However, longer exposure (90 min)
      increased the excitor responses, similarly to the effects of GAD blockers. 9.
      Baclofen, a gamma-aminobutyric acid-B (GABAB) agonist, antagonized AOAA effects
      on evoked inhibition. 10. These results demonstrate that GAD blockers decrease
      postsynaptic and presynaptic inhibition by reducing both tonic and evoked
      release, most likely by diminishing p. 11. The reduction in GABA synthesis and
      release revealed a complex mechanism for GABAergic metabotropic regulation of
      inhibition efficacy and the release from the excitor glutamatergic terminals.

PMID- 8734606
TI  - Parabrachial area: electrophysiological evidence for an involvement in cold
      nociception.
AB  - 1. Thirty-five percent of 120 neurons recorded extracellularly in the
      parabrachial (PB) area of anesthetized rats responded to a peripheral cold
      stimulus (0 degrees C). The cold-sensitive neurons were located in the lateral PB
      area, and most of those exhibiting a strong response to cold stimuli were inside
      or in close vicinity to the area receiving a high density of projections from
      superficial neurons of the dorsal horn. 2. The receptive fields for cold
      stimulation often were restricted to one or two parts of the body with a
      contralateral predominance for the limbs. No side predominance was observed for
      the face. 3. From a low spontaneous activity (10th percentile < median < 90th
      percentile: 0.1 < 1.5 < 5 Hz), the PB neurons responded to cold noxious stimuli
      (0 degree C water bath or waterjet, 20 s), without observable delay, with a
      sustained discharge. The mean maximal response to the stimulus was 16.1 +/- 1.2
      Hz (mean +/- SE; n = 42). 4. About one-half (45%) of these cold-sensitive neurons
      were activated specifically by cold stimulation and did not respond or were
      inhibited by noxious heat and/or pinch. The remaining (55%) cold-sensitive
      neurons were also driven by heat and/or pinch. 5. The cold-sensitive neurons
      exhibited a clear capacity to encode cold stimuli in the noxious range: the
      stimulus-response function was always positive and monotonic from 30 to 0 degrees
      C; the mean curve was linear between 20 and 0 degrees C before plateauing between
      0 to -10 degrees C; the mean threshold to cold stimulation was 17.1 +/- 1 degrees
      C (n = 21) and the mean t50 was 10.7 +/- 1.1 degrees C (n = 13). 6. The cold
      sensitive neurons responded to intense transcutaneous electrical stimulation with
      an early and/or a late peak of activation, the latencies of which were in the 15
      50 ms and 80-170 ms ranges (n = 8), respectively, i.e., compatible with the
      activation of A delta and C fibers. Interestingly, the cold-specific neurons
      predominantly responded with a late peak, suggesting these neurons were primarily
      driven by peripheral C fibers. 7. The intravenous injection of morphine depressed
      the responses of PB neurons to cold noxious stimuli in a dose-related (1, 3, and
      9 mg/kg) and naloxone reversible fashion. The ED50 value was estimated
      approximately 2 mg/kg. Furthermore, two populations of neurons could be separated
      according to their morphine sensitivity. 8. It is concluded that PB cold
      nonspecific neurons could be involved in affective-emotional, autonomic and
      neuroendocrine reactions in response to noxious cold events. The PB cold-specific
      neurons could be, in addition, involved in some thermoregulatory processes.

PMID- 8734607
TI  - Electrical filtering in gerbil isolated type I semicircular canal hair cells.
AB  - 1. Membrane potential responses of dissociated gerbil type I semicircular canal
      hair cells to current injections in whole cell current-clamp have been measured.
      The input resistance of type I cells was 21.4 +/- 14.3 (SD) M omega, (n = 25).
      Around the zero-current potential (Vz = -66.6 +/- 9.3 mV, n = 25), pulsed current
      injections (from approximately -200 to 750 pA) produced only small-amplitude,
      pulse-like changes in membrane potential. 2. Injecting constant current to
      hyperpolarize the membrane to around -100 mV resulted in a approximately 10-fold
      increase in membrane resistance. Current pulses superimposed on this constant
      hyperpolarization produced larger and more complex membrane potential changes.
      Depolarizing currents > or = 200 pA caused a rapid transient peak voltage before
      a plateau. 3. Membrane voltage was able to faithfully follow sine-wave current
      injections around Vz over the range 1-1,000 Hz with < 25% attenuation at 1 kHz. A
      previously described K conductance, IKI, which is active at Vz, produces the low
      input resistance and frequency response. This was confirmed by pharmacologically
      blocking IKI. This conductance, present in type I cells but not type II hair
      cells, would appear to confer on type I cells a lower gain, but a much broader
      bandwidth at Vz, than seen in type II cells.

PMID- 8734608
TI  - Taste-mixture suppression: functional dissection of cellular and paracellular
      origins.
AB  - 1. Chorda tympani (CT) nerve responses were recorded during simultaneous current
      and voltage clamping of the lingual receptive-field epithelium to examine the
      role of field potential in taste mixture suppression between sodium gluconate
      (NaG) and potassium gluconate (KG). 2. Under zero current-clamp conditions, CT
      responses to 100 mM NaG were suppressed by 63% when presented in mixture with 250
      mM KG. At this concentration, KG alone elicited no measurable neural activity,
      but produced a large submucosal-positive field potential. 3. When CT responses to
      100 mM NaG were obtained with voltage clamp at the zero-current clamp field
      potential of the NaG/KG mixture, they were suppressed by only 30% relative to NaG
      responses under zero-current clamp. Similarly, CT responses to the mixture of NaG
      and KG measured while voltage was clamped at the field potential of NaG alone
      were slightly elevated, but not to the magnitude of zero-current clamp responses
      to NaG. Therefore field potential-mediated suppression of CT responses to NaG
      accounts for only a part of the total mixture suppression between NaG and KG. 4.
      Analysis of the voltage dependence of CT responses to NaG indicated that the
      moderate field potential increase (8.9 mV) caused by the presence of KG in the
      mixture equates to a 43% increase in the apparent Km for NaG, from 110 to 157 mM.
      Use of this effective Km obviated the effect of field potential on CT responses
      to the NaG/KG mixture and permitted kinetic analysis of K+ blockade of Na+
      responses. These analyses suggested that K ions block Na+ movement through apical
      Na+ channels in a voltage-independent manner with an apparent Ko of 405 mM.
      Importantly, direct inhibition of Na+ transduction by K+ can account for the part
      of mixture suppression not mediated by field potential. 5. These experiments
      reveal that mixture suppression between NaG and KG is derived from two distinct
      sources. Field potential, triggered largely by the limited mobility of both K+
      and Na+ through taste bud tight junctions, globally modulates Na+ transduction.
      In addition, at the level of the apical Na+ channel, K ions directly block
      movement of depolarizing Na+ across taste receptor apical membranes.

PMID- 8734609
TI  - Computer simulations of voltage clamping retinal ganglion cells through whole
      cell electrodes in the soma.
AB  - 1. Computer simulations of voltage-clamp experiments in retinal ganglion cells
      were implemented to better understand the insights that can be obtained with this
      physiological approach. 2. Simulation studies of voltage clamping were based on
      the contemporary approach of using whole-cell recordings with low resistance
      electrodes attached to the soma. Realistic ganglion cell morphologies were
      provided by cell staining experiments in the mudpuppy retina; selected cells
      included small-, medium-, and large-field neurons whose morphologies were entered
      into a computer through a neuron tracing program. 3. Values for the specific
      membrane resistance (Rm) varied from 5,000 to 100,000 omega/cm2 to conform to the
      range of Rm values obtained with intracellular sharp electrodes and whole-cell
      recordings. 4. Synaptic input currents were simulated by injecting current with
      and without an underlying conductance change into different regions of the
      dendritic tree. The time-variant waveform of the current included a combined
      transient and sustained component similar to the waveform of ON-bipolar
      activation. 5. Simulations were base on 1) intact structures, which included the
      soma and the entire dendritic tree, and 2) a more limited cell geometry that
      included representation of the soma, but only part of the dendritic tree, to
      represent the restricted morphology that might be rendered after cutting the
      retina into 150-microns cross sections for retinal slice experiments. 6. The
      results of this study indicate that voltage clamping from the soma, with optimal,
      low resistance electrodes and series resistance compensation, provides an error
      free voltage clamp for slow signals that are generated within a small
      electrotonic distance from the soma (approximately 0.1 lambda). 7. The ideal
      voltage-clamp conditions are optimized when synaptic conductances are small and
      nonlinear membrane elements are minimally activated: small-field neurons best
      approximate these conditions, but clamping errors are evident in these cells when
      more distal branches are activated. The degree of error in voltage clamping was
      much greater when medium-and large-field neurons were evaluated. 8. It was not
      possible to clamp action potentials (nonpropagating) even when they were
      generated near the soma in any of the three model cells examined. 9. Experimental
      paradigms were developed to demonstrate that inadequate voltage clamping can lead
      to errors in the interpretation of experimental data when relevant variables are
      not taken into consideration. Suggestions are made for determining and optimizing
      favorable clamp conditions.

PMID- 8734610
TI  - Reorganization of movement representations in primary motor cortex following
      focal ischemic infarcts in adult squirrel monkeys.
AB  - 1. Intracortical microstimulation (ICMS) techniques were used to derive detailed
      maps of distal forelimb movement representations in primary motor cortex (area 4)
      of adult squirrel monkeys before and a few months after a focal ischemic infarct.
      2. Infarcts caused a marked but transient deficit in use of the contralateral
      hand, as evidenced by increased use of the ipsilateral hand, and reduced
      performance on a task requiring skilled digit use. 3. Infarcts resulted in a
      widespread reduction in the areal extent of digit representations adjacent to the
      lesion, and apparent increases in adjacent proximal representations. 4. We
      conclude that substantial functional reorganization occurs in primary motor
      cortex of adult primates following a focal ischemic infarct, but at least in the
      absence of postinfarct training, the movements formerly represented in the
      infarcted zone do not reappear in adjacent cortical regions.

PMID- 8734611
TI  - Application of the GABA antagonist bicuculline to the premotor cortex reduces the
      ability to withhold reaching movements by well-trained monkeys in visually guided
      reaching task.
AB  - 1. A gamma-aminobutyric acid (GABA) antagonist, bicuculline methiodide (BMI, 10
      micrograms/microliters, 1 microliter), was locally injected into a total of 32
      sites in the right premotor cortex (PM) of two rhesus monkeys that had been well
      trained in a visually guided reaching task (VR) for approximately 3 yr. The
      monkey initiated the task by pressing a central hold lever with its left hand,
      and this was followed by waiting (1 s), warning (central green square on a
      computer monitor, 0.5 s), cue (right, upper, or left square), delay (2-5 s), and
      go (central green square changes to red, < 1.2 s) periods. In the go period, the
      monkey released the hold lever and reached out to one of three target levers
      (left, upper, or right) that had been indicated 2-5 s previously in the cue
      period. 2. At three sites in the dorsal part of the PM, after the local
      application of BMI, reaching movements of the left forelimb, which were not part
      of the trained-reaching, occurred 200-300 ms after the onset of a burst of
      neuronal activity at the BMI injection site. This induced-reaching, which was
      designated a "forced-reaching" movement, occurred while the monkeys were pressing
      the hold lever before the cue appeared-i.e., during the waiting or waiting
      period. No reaching occurred when the burst did not appear. Furthermore,
      trajectories and electromyograms of the forelimbs during the forced-reaching
      movements were similar to those in the trained-reaching movements in the VR task.
      3. These results suggest that restricted sites in the dorsal PM of monkeys are
      involved in the initiation and/or execution of trained-reaching movements and
      that GABAergic inhibition at these sites normally suppresses this
      initiation/execution unless it is required. By relaxing GABAergic suppression,
      the dorsal PM might send a command to a neuronal system that is associated with
      trained reaching to recruit the system, thereby initiating and/or executing the
      trained reaching.

PMID- 8734612
TI  - Long-lasting potentiation and depression without presynaptic activity.
AB  - 1. Long-term potentiation (LTP) and long-term depression (LTD) require a rise in
      intracellular Ca2+ concentration ([Ca2+]i) in the postsynaptic CA1 pyramidal
      neuron to activate Ca-dependent biochemical processes. This rise in [Ca2+]i is a
      necessary trigger for the induction of LTP and LTD, but it is unclear if
      concurrent presynaptic activity is required for their induction or expression. 2.
      We used photolysis of the caged-Ca2+ compound nitr-5 to elevate postsynaptic
      [Ca2+]i. Long-lasting potentiation (LLP) and long-lasting depression (LLD) were
      obtained in the absence of presynaptic activity. 3. Because LLP and LLD share
      common features with LTP and LTD induced by presynaptic stimulation these results
      show that a rise in [Ca2+]i in the postsynaptic CA1 pyramidal neurons is
      necessary and sufficient for the induction and expression of LTP and LTD, and
      that concurrent presynaptic activity is not required.

PMID- 8734613
TI  - Sign stimulus activates a peptidergic neural system controlling reproductive
      behavior in Aplysia.
AB  - 1. In the marine mollusk Aplysia, egg laying is a complex behavior that lasts for
      up to several hours. We used behavioral and electrophysiological methods to
      determine how egg laying occurs in groups of animals and how it is related to
      other aspects of reproductive behavior. 2. Prolonged contact with an existing egg
      mass by the lips and tentacles of an animal is a sign stimulus for release of egg
      laying behavior and two other fixed action patterns in the same individual,
      mating as a female during egg laying and mating as a male after egg laying. 3.
      Prolonged contact with the egg mass initiated repetitive spike activity in bag
      cell neurons, which are part of a peptidergic neural system that modulates
      neuronal activity in the CNS for up to several hours. The sign stimulus thus
      activates the neuromodulatory system, which may serve as an innate releasing
      mechanism, and an associated internal drive, for control of the behavioral
      sequence.

PMID- 8734614
TI  - Intracellular blockade of inhibitory synaptic responses in visual cortical layer
      IV neurons.
AB  - 1. Inhibitory postsynaptic potentials (IPSPs) evoked by stimulation at the white
      matter/layer VI border were recorded intracellularly from visual cortical layer
      IV neurons maintained in vitro. These IPSPs, typically not apparent at resting
      membrane potentials, were measured at membrane potentials 15-25 mV depolarized
      from resting levels. The effects of two chloride channel blockers on these IPSPs
      were investigated. 2. 4,4'-Dinitro-stilbene-2,2'-disulfonic acid (DNDS) was found
      to inhibit IPSPs as it diffused into the postsynaptic cell from an intracellular
      micropipette, leaving only the presumed pure excitatory postsynaptic potential
      (EPSP) component of the evoked compound PSP. Input resistance, resting membrane
      potential, spike accommodation, and EPSPs at resting membrane potentials were not
      significantly affected. 3. A novel chloride channel blocker 5,11,17,23
      tetrasulfonato-25,26,27,28-tetramethoxy-calix[4]a rene (TS-TM-calix[4]arene) was
      found to potently inhibit IPSPs recorded at depolarized membrane potentials. The
      TS-TM-calix[4]arene, similar to DNDS, did not affect input resistance, resting
      membrane potential, spike accommodation, and EPSPs at resting membrane
      potentials. 4. To confirm that DNDS and TS-TM-calix[4]arene were indeed blocking
      IPSPs, similar experiments were performed on monosynaptic IPSPs evoked by
      stimulation of layer V in the presence of 2-amino-5-phosphonovaleric acid (APV)
      and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Both DNDS and TS-TM
      calix[4]arene were effective in blocking monosynaptic IPSPs. 5. Consistent with
      the notion that DNDS and TS-TM-calix[4]arene block IPSPs by inhibiting gamma
      aminobutyric acid-A (GABAA) receptor channels, the decrease in input resistance
      caused by extracellular application of muscimol was also significantly inhibited
      by intracellular use of these compounds. 6. These data suggest that DNDS and TS
      TM-calix[4]arene applied intracellularly may be useful for the study of the
      function of GABAA-mediated synaptic inhibition of cortical neurons. Because only
      neurons impaled by the recording electrodes are influenced by the drugs, this
      method offers an advantage over extracellular application of GABAA blockers in
      that entire networks of neurons are not influenced.

PMID- 8734615
TI  - Cloning of a novel component of A-type K+ channels operating at subthreshold
      potentials with unique expression in heart and brain.
AB  - 1. Proteins of the Kv4 or Shal-related subfamily are key components of transient
      K+ channels (A channels) operating at subthreshold values of the membrane
      potential. We have cloned and characterized a new mammalian Kv4 or Shal-related
      cDNA (Kv4.3) that predicts a protein with strong sequence conservation with the
      other known members of this subfamily. 2. Injection of Kv4.3 transcripts into
      Xenopus oocytes generates an A type K+ current, with small but physiologically
      significant differences from the currents expressed by Kv4.2 and Kv4.1 mRNAs.
      Kv4.3 currents can be modified to resemble native A currents by coinjection with
      a low molecular weight mRNA fraction from rat brain which does not express
      detectable currents on its own. Particularly striking is a 7-to-10-fold increase
      in the rate of recovery from inactivation, a 5- to 10-fold increase in current
      magnitude and a 3- to 4-fold increase in sensitivity to 4-amino pyridine (4-AP).
      3. In situ hybridization histochemistry was used to compare the expression of the
      three known Kv4 genes. Kv4.2 and Kv4.3 (but not Kv4.1) are abundant in the adult
      rat brain, with each displaying a specific, but sometimes overlapping pattern of
      expression. Moreover, a reciprocal gradient of expression of Kv4.2 and Kv4.3
      transcripts is seen in some brain areas, such as in the pyramidal cell layers of
      the hippocampus and the granule cell layer of the cerebellum. Therefore Kv4
      proteins may form heteromultimeric channels of distinct subunit composition in
      different neurons. Moreover, the results suggest that neurons such as pyramidal
      cells in the hippocampus and granule cells in the cerebellum represent
      heterogeneous cell populations in terms of their ISA, and hence in their firing
      patterns. Kv4.2 and Kv4.3 also display complementary expression in the heart,
      with Kv4.3 being more abundant in atria and Kv4.2 in ventricle. The existence of
      multiple Kv4 proteins forming channels of variable subunit combinations helps
      explain the diversity of ISA channels in neurons.

PMID- 8734616
TI  - Parietal neurons related to memory-guided hand manipulation.
AB  - 1. We recorded activity of the hand-manipulation-task-related neurons in the
      posterolateral bank of the anterior intraparietal sulcus (area AIP) of the monkey
      parietal cortex during a delayed hand manipulation task. 2. We examined mainly
      the object-type visual-dominant and visual-and-motor neurons that responded to
      the sight of objects for manipulation. The majority of these neurons (32 of 48)
      showed sustained activity during the delay period in the dark before manipulation
      of preferred objects. 3. Six visual-and-motor neurons showed set-related activity
      before the hand manipulation in the dark, so that their delay period activity was
      likely to be related to motor preparation. 4. The delay period activity of 18
      visual-dominant and visual-and-motor neurons without set-related activity was
      likely to represent spatial features of objects, because the majority of the
      neurons showed the same selectivity in the shape and/or orientation during object
      fixation and the delay period. 5. Of these 18 neurons, 10 showed sustained
      activity in the dark after brief illumination of objects during a light
      interrupted fixation task, suggesting that they store the short-term memory of
      objects without the intention to remember. 6. The results suggest that the visual
      memory of three-dimensional features of objects is likely to be incorporated in
      area AIP and to be used for the guidance of hand manipulation.

PMID- 8734617
TI  - Visually guided saccade versus eye-hand reach: contrasting neuronal activity in
      the cortical supplementary and frontal eye fields.
AB  - 1. We studied neuronal activity in the supplementary eye field (SEF) and frontal
      eye field (FEF) of a monkey during performance of a conditional motor task that
      required capturing of a target either with a saccadic eye movement (the saccade
      only condition) or with an eye-hand reach (the saccade-and-reach condition),
      according to visual instructions. 2. Among 106 SEF neurons that showed
      presaccadic activity, more than one-half of them (54%) were active preferentially
      under the saccade-only condition (n = 12) or under the saccade-and-reach
      condition (n = 45), while the remaining 49 neurons were equally active in both
      conditions. 3. By contrast, most (97%) of the 109 neurons in the FEF exhibited
      approximately equal activity in relation to saccades under the two conditions. 4.
      The present results suggest the possibility that SEF neurons, at least in part,
      are involved in signaling whether the motor task is oculomotor or combined eye
      arm movements, whereas FEF neurons are mostly related to oculomotor control.

PMID- 8734618
TI  - Active tactile exploration influences the functional maturation of the
      somatosensory system.
AB  - 1. The hypothesis that active exploration of objects is required for the
      functional maturation of neuronal circuits subserving tactile perception was
      tested by subjecting 8- to 11-day old rats to a complete unilateral section of
      the facial nerve. This procedure selectively abolished whisker protraction
      movements without affecting the sensory innervation of the facial vibrissae, the
      tactile organs used by rats to discriminate object texture and shape. 2. Six to
      14 mo after the facial nerve section, simultaneous recordings of neuronal
      ensembles located in the ventral posterior medial nucleus (VPM) of the thalamus
      revealed a marked reduction in receptive field (RF) size (in terms of number of
      whiskers), and the formation of abnormal RF surrounds, spanning the face and
      contiguous body regions. In addition, the directional organization of VPM RFs,
      represented by caudal to rostral shifts in RF centers over 30 ms following
      whisker stimulation, was greatly reduced in these animals. 3. These results
      suggest that neonatal active tactile exploration is required to establish normal
      spatiotemporal patterning of neuronal RFs within the somatosensory system, and
      consequently, to develop normal tactile perception.

PMID- 8734619
TI  - Annual update on legislative issue.

PMID- 8734620
TI  - The National Labor Relations Board (NLRB)

PMID- 8734621
TI  - Nurse-managed cancer-screening clinic.
AB  - As many institutions are reconfiguring the work environment to compete within the
      managed care arena, nurse-managed clinics can be one cost-effective option in
      which advanced practice nurses can further enhance the quality and efficiency of
      health care services provided by the primary care physicians in this everchanging
      health care arena.

PMID- 8734622
TI  - Speculoscopy: a tool to enhance the detection of abnormal vaginal and cervical
      cells.

PMID- 8734623
TI  - Failure to thrive: an ambulatory approach.
AB  - The diagnosis and management of failure to thrive, a multifactorial condition,
      can be a challenge for the primary care provider. This article deals with organic
      failure to thrive and nonorganic failure to thrive in ambulatory settings. The
      complex etiology of failure to thrive is addressed relative to maternal/paternal
      and infant/child characteristics. Physical assessment is addressed with special
      attention on critical growth measurements, feeding and eating patterns,
      developmental delays, and psychosocial issues. Interventions in the areas of
      nutrition, development, and psychosocial interactions are examined with an
      emphasis on team management. Long-term effects of failure to thrive and primary
      and secondary preventive interventions are addressed.

PMID- 8734624
TI  - Recurrent aphthous stomatitis: primary care management.
AB  - Recurrent aphthous stomatitis (RAS), often referred to as canker sore, is a
      chronic inflammatory disease. Frequently seen in the primary care setting, RAS
      affects over 50% of the population and may be observed in an otherwise apparently
      healthy individual. An unknown pathogenesis and absence of curative treatment
      make RAS a challenge to manage. Treating RAS should be patient specific and focus
      on reduction of pain and lesions. An awareness of literature suggesting
      etiologies, precipitating, and predisposing factors can assist the practitioner
      and patient in controlling RAS episodes. Contained in this review is a suggested
      course of management for patients with RAS, including present recommendations for
      pharmacological interventions.

PMID- 8734625
TI  - A national survey of nurse practitioner chlamydia knowledge and treatment
      practices of female patients.
AB  - Chlamydia is the most prevalent sexually transmitted disease in the United
      States, with over 4 million new infections presenting each year. The disease
      presents disproportionate problems for women who are generally asymptomatic;
      chlamydia is more difficult to diagnose in women than men. Untreated infections
      in women evolve into serious reproductive tract sequelae, including pelvic
      inflammatory disease, chronic pain, infertility, ectopic pregnancy, and neonatal
      complications. The bright side to this epidemic is that these sequelae are
      preventable. Chlamydia is both treatable and easily cured when it is detected. A
      national mailed survey of NPs was conducted to ascertain current chlamydia
      knowledge levels and clinical practices with female patients. Survey findings
      indicate that NPs are fairly knowledgeable about the infection and NP clinical
      practices are generally consistent with Centers for Disease Control and
      Prevention recommendations for chlamydia diagnostics and treatment. However, the
      survey identified NP deficits in screening and treatment practices for pregnant
      women. These findings are disturbing given the serious risks associated with
      failure to promptly diagnose and treat prenatal infections. The survey highlights
      the need for continuing professional education about chlamydia and other sexually
      transmitted infections.

PMID- 8734626
TI  - Women and heart attacks: prevention, diagnosis, and care.
AB  - Despite being viewed as a male health problem, more women die from heart disease
      than men. The literature and preliminary research data reviewed clearly support
      that gender differences exist. The higher prevalence of myocardial infarction in
      older women and those with other known risk factors suggests the etiology,
      pathophysiology, and treatment is the same as for men. Differences in
      socioeconomic status, psychosocial profiles, presenting symptoms, disease
      progression, and a poorer response to treatment suggests that myocardial
      infarction in women is not fully understood. Women need to know they are at risk
      and not delay seeking treatment for subtle but important symptoms. Assessment
      strategies that take into account the woman's body, personal profile, and the
      female pattern of variant angina, non-Q wave, nonocclusive infarction are
      reviewed. Considering the literature that links social support with survival,
      mobilizing support to help the women direct energies to her own recovery becomes
      a necessary intervention. Implications to health teaching, diagnostic testing,
      diagnosis, referral, and the effective management of women with myocardial
      infarction are delineated.

PMID- 8734627
TI  - Acute otitis media in children.
AB  - Acute otitis media, a common childhood disorder, is an inflammation of the middle
      ear. It is the most frequent diagnosis made in primary care settings for children
      under 15 years of age. Almost all children are afflicted with at least one
      episode of otitis media before age 6. Diagnosis can often be challenging,
      especially in infants and toddlers. Moreover, management controversies exist.
      This article addresses the epidemiology, clinical presentation, and diagnosis of
      acute otitis media and presents treatment options based on results of recent
      research. When a child is diagnosed with acute otitis media, it behooves the
      clinician to use sound research-based clinical judgment in prescribing treatment.

PMID- 8734628
TI  - Adult screening for depression.

PMID- 8734629
TI  - The hypertensive elder: a review for the primary care provider.
AB  - Hypertension, the most prevalent cardiovascular disorder in America, affects over
      50% of the older adult population. Management of hypertension in the elder is
      influenced by numerous age-related factors, including physiological changes, co
      morbid conditions, functional or cognitive impairments, and polypharmacy issues.
      As data on the damaging effects of untreated hypertension increase, practice
      guidelines are increasingly focused on early detection and successful management
      of blood pressure in the primary care setting. The primary health care provider,
      having an advanced knowledge base and excellent communication skills, can make
      effective management of hypertension a reality. This article presents a
      comprehensive review of assessment, diagnosis, and treatment of hypertension in
      the older adult. Lifestyle modification and pharmacologic therapy are discussed.
      Elements of patient education are described, with special emphasis on promoting
      adherence to a long-term treatment regimen.

PMID- 8734630
TI  - College health providers' knowledge, attitudes, and management practices of
      genital HPV infection.
AB  - This comparative survey of college health providers explored nurse practitioners'
      (N = 73) and physicians' (N = 70) knowledge, attitudes, and management practices
      related to genital human papillomavirus (HPV) infection in females. Both groups
      had adequate knowledge of basic issues of HPV epidemiology, diagnosis, and
      treatment. Divergent attitudes and management practices were reported among the
      providers, with generally low agreement with national STD treatment guidelines
      published by the Centers for Disease Control and Prevention (CDC). Generally,
      providers tended to practice a more aggressive management approach on several
      aspects of HPV infection than recommended by the CDC guidelines. The one major
      exception reported by the majority of providers was the conservative use of
      colposcopy for identifying subclinical HPV infection in patients with external
      genital warts, a finding consistent with CDC guidelines. The availability of
      colposcopy within a provider's health center was found to be associated with the
      reported use of colposcopy. Recommendation for future research and implications
      for college health and advanced nursing practice are addressed.

PMID- 8734631
TI  - Alprostadil for the treatment of erectile dysfunction.

PMID- 8734632
TI  - Cystic fibrosis: malabsorption associated with pancreatic insufficiency.

PMID- 8734633
TI  - Job description for primary care nurse practitioners.

PMID- 8734634
TI  - Comparison of virulence of different Actinobacillus pleuropneumoniae serotypes
      and biotypes using an aerosol infection model.
AB  - An aerosol infection model for inoculation of pigs with Actinobacillus
      pleuropneumoniae is described. With this model the virulence of three A.
      pleuropneumoniae biotype 1 strains representing serotypes 2, 5b and 6, and one
      Danish biotype 2 were compared using 13-week-old pigs for inoculation. The pigs
      were sacrificed 24 h after aerosol exposure and lung lesions were evaluated. In
      pigs exposed to aerosols of suspensions containing 10(4) CFU/ml of serotypes 2,
      5b and 6, a number of 5-10 lesions of haemorrhagic necrotizing pneumonia were
      induced. For the biotype 2 strain the dose creating similar lesions was 10(9)
      CFU/ml. Repeated experiments confirmed these results showing similar virulence of
      serotypes 2, 5b and 6 whereas the biotype 2 strain proved less virulent. The
      aerosol infection model allowed a comparison of the number of A. pleuropneumoniae
      CFU/liter air which were necessary to induce lung lesions in susceptible pigs.
      This indicates that the model will be well suited for virulence studies of A.
      pleuropneumoniae serotypes in pigs.

PMID- 8734635
TI  - Studies on the cell tropism of Listeria monocytogenes in ovine fetal brain cell
      cultures.
AB  - The uptake of Listeria monocytogenes by cells in primary dissociated brain cell
      cultures prepared from ovine fetuses at approximately 50 to 60 days of gestation
      was studied using a sequential double immunofluorescence technique with
      antibodies against cell type-specific markers and the bacterial pathogen. Cell
      cultures were inoculated with bacteria at day 4, 8, and 15 in vitro. Listeria
      monocytogenes was predominately internalized by CD68-positive macrophages,
      followed by astrocytes, fibronectin-expressing cells, and neurons. An uptake of
      the bacterium by galactocerebroside (GC)-positive oligodendrocytes, which were
      first detected at day 15 in vitro, did not occur. Although a tropism for neurons
      was not observed, the susceptibility of neurons for infection with Listeria
      monocytogenes is in accordance with the supposed intraaxonal migration of the
      bacterium in the pathogenesis of focal brain stem encephalitis. The pattern of
      the infection rates of ovine brain cell types was similar to that shown in murine
      fetal brain cell cultures, indicating that there is no species-specific brain
      cell tropism of the bacterium.

PMID- 8734636
TI  - Comparative evaluation of antibodies induced by commercial Pasteurella
      haemolytica vaccines using solid phase immunoassays.
AB  - The objective of this study was to evaluate the ability of four commercial
      vaccines to elicit antibodies against the leukotoxin (Lkt), capsular
      polysaccharide (CP), iron regulated outer membrane proteins (IROMPs), and whole
      cell (WC) antigens of Pasteurella haemolytica A1. Modified double antibody
      sandwich enzyme linked immunosorbent assays (ELISAs) were developed to measure
      antibody levels against Lkt, CP and IROMPs. An indirect ELISA was developed to
      measure the levels of antibody against WC antigens. The ideal cut off points for
      ELISAs were determined on receiver operating characteristic curves, using sera
      from 30 calves injected subcutaneously with a live P. haemolytica 12296 strain as
      positive control and sera from 30 colostrum-deprived calves as negative control.
      The vaccines evaluated were: 'One Shot' (SmithKline Beecham, West Chester, PA) a
      bacterin-toxoid, 'Presponse' (Langford Laboratories, Guelph, Ontario) a Lkt-rich
      culture supermatant, 'Once PMH' (BioCor Inc., Omaha, NE) a modified live vaccine,
      and 'Septimune' (Fort Dodge laboratories, Fort Dodge, IA) an outer membrane
      extract. Thirty, 4-6 week old Holstein calves were randomized into 5 groups to
      receive one of the four vaccines or a placebo (sterile phosphate buffered
      saline). The calves were vaccinated intramuscularly on day 0 and on day 14, and
      bled on days, 0, 14, and 28 to measure antibody levels against Lkt, CP, IROMPs,
      and WC antigens of P. haemolytica Al. 'One Shot', and 'Once PMH' vaccinates
      showed a significant (P < 0.05) increase in antibody levels against Lkt at 28
      days. 'Once PMH' vaccinates also showed significant (P < 0.05) increase in
      antibody levels against IROMPs at 28 days compared to the other four groups but
      this increase was not significant over time within the 'Once PMH' group.
      'Presponse', 'Once PMH' and 'One Shot' vaccinates showed a significant (P < 0.05)
      increase in antibody levels against CP over time. These groups also had
      significantly higher antibody levels against CP, compared to controls and
      'Septimune' vaccinates at 14 and 28 days (P < 0.05).

PMID- 8734637
TI  - In vitro and in vivo phenotypes resulting from deletion of the high temperature
      requirement A (htrA) gene from the bovine vaccine strain Brucella abortus S19.
AB  - An htrA deletion mutant was created in the bovine vaccine strain, B. abortus S19,
      by replacing the majority of the htrA gene with a kanamycin resistance gene.
      Antibiotic selection for a double crossover event yielded kanamycin-resistant,
      ampicillin-sensitive colonies confirmed by Southern and western blot analysis to
      be HtrA deficient. The B. abortus S19 htrA mutant was significantly more
      susceptible than the parental strain to killing by H2O2 (P < 0.001) and O(2)-
      generated by the redox cycling agent paraquat (P < 0.05) in disk sensitivity
      assays. Deletion of the htrA gene from S19 produced a bimodal effect on the
      spleen colonization profile of this strain in BALB/c mice. At one week post
      infection, the B. abortus S19 htrA mutant colonized the spleens of experimentally
      infected BALB/c mice at significantly lower levels (P < 0.01) than the parental
      strain. Enhanced clearance (P < 0.05) was also observed at later timepoints, i.e.
      4 and 7 weeks post infection, however at 2 and 3 weeks post infection, the mutant
      and parental strains colonized the mice at equivalent levels. The temporal
      development of specific delayed type hypersensitivity and antibody responses in
      BALB/c mice infected with the mutant or parental strain were equivalent. These
      results suggest that the htrA gene product contributes to successful host
      colonization by S19. However, deletion of this gene does not radically alter the
      overall, characteristic spleen colonization profile of this vaccine strain in the
      BALB/c mouse model, nor compromise the capacity of this strain to elicit Brucella
      cellular or humoral immune responses in this experimental host.

PMID- 8734638
TI  - Serogroups, toxins and antibiotic resistance of Escherichia coli strains isolated
      from diarrhoeic lambs in Spain.
AB  - One hundred and forty-four Escherichia coli strains isolated from 144 diarrhoeic
      lambs (5 to 21 days old) from 38 flocks in Spain were serotyped and investigated
      for production of enterotoxins (LT and STa), verotoxins (VT1 and VT2), cytotoxic
      necrotizing factors (CNF1 and CNF2), alpha-haemolysin (Hly) and enterohaemolysin
      (EntHly), for necrotic and lethal activities and for antibiotic resistance. The
      strains belonged to 39 different serogroups; however, 58% were of one of 13
      serogroups (O4, O6, O7, O8, O9, O11, O23, O26, O77, O80, O101, O103 and O161) and
      only four of them (O8, O9, O11 and O77) accounted for 34% of strains. In total 10
      (7%) toxigenic strains were detected: two LT+, two VT1+ EntHly+, four VT1+ EntHly
      , one CNF1+ Hly+ and one CNF2+. The highest percentages of antibiotic resistance
      were reached in the group of antibiotics (tetracycline, streptomycin,
      sulphadiazine, ampicillin, kanamycin, neomycin, chloramphenicol, trimethoprim and
      cotrimoxazole) that are most generally used by Spanish veterinary clinics. We
      conclude that E. coli strains isolated from diarrhoeic lambs are not generally
      toxigenic and belong to a large number of serogroups.

PMID- 8734639
TI  - Evidence for phospholipase B activity in Fusobacterium necrophorum cultures and
      its association with hemolysin/leucocidin activities.
AB  - Phospholipase B (PLB) activity was present in Fusobacterium necrophorum cultures
      and it correlated closely with virulence and co-purified with the
      hemolysin/leucocidin activities. All three activities were associated with a
      large molecule or molecular complex (6 x 10(2)-2 x 10(3) kDa) exhibiting varying
      degrees of aggregation. These were present mainly in the culture medium and to a
      lesser extent in cell sonicates. The PLB and toxin activities were sensitive to
      heat, dissociating agents, proteolytic enzymes, prolonged purification regimes,
      freeze-drying and repeated freeze-thawing. The toxin(s) were stable over a broad
      range of pH, did not require divalent ions or reducing agents and could be kept
      for several months as an ammonium sulfate precipitate at 4 degrees C, or stored
      as a concentrated liquid in the presence of proteolytic inhibitors at - 20
      degrees C.

PMID- 8734640
TI  - CNF producing Escherichia coli isolated from cattle in Northern Ireland.
AB  - Tissue culture assays were used to investigate the incidence of cytotoxic
      necrotising factors (CNFs) 1 and 2 in Escherichia coli strains from cattle. E.
      coli cultures were obtained from faeces collected from 223 cases of diarrhoea and
      from 113 healthy animals. In addition, strains cultured from 62 cases of
      mastitis, 66 cases of septicaemia and 68 cases of abortion were also
      investigated. E. coli producing CNF 1 or 2 were identified in all sample groups
      except for the abortion cases. Comparable levels of CNF1 strains were present in
      E. coli from the faces of diarrhoeic (4%) and healthy faeces (4.4%) whereas lower
      levels of CNF2 were identified in the faeces from diarrhoeic animals (19.3%) in
      comparison with healthy animals (30.9%). One CNF1 producing strain was identified
      among the E. coli isolated from mastitis samples, while 3% and 10.6% of
      septicaemic strains were positive for CNF1 and 2, respectively. Serogrouping of
      CNF isolates did not reveal the association of any particular serogroups with the
      different conditions.

PMID- 8734641
TI  - Reactive nitrogen intermediates production from naive and activated monocytes by
      extracts of Mycobacterium bovis BCG.
AB  - Extracts of Mycobacterium bovis strain BCG were assessed for in vitro activation
      of monocytes to produce reactive nitrogen intermediates. The culture filtrate of
      M. bovis BCG was a strong inducer of nitrite production while live BCG and
      sonicated antigens were also potent inducers. Other extracts activated monocytes
      which showed an increase in nitrite production after in vitro BCG infection.

PMID- 8734642
TI  - Replication of Australian porcine isolates of Ileal symbiont intracellularis in
      tissue culture.
AB  - Ileal symbiont intracellularis (ISI) isolated from Australian cases of PIA and
      PHE was replicated in the rat ileum enterocyte cell line IEC 18. The number of
      ISI within cells varied, as did the number of ISI infected within the monolayer.
      At 24 h post infection a large number of cells were infected with approximately
      100 ISI per cell. At the termination of infection, fewer IEC 18 cells were
      infected but ISI had replicated to fill the cell cytoplasmic space. Numerous foci
      of infected cells were visible in the monolayer, containing as many as 15 densely
      infected cells. Division of ISI infected cells indicated the transmission of ISI
      in the cytoplasm to daughter cells. This suggests that the replication of ISI in
      culture appears to be reasonably cell dependent. No cytopathic effects were
      observed in the infected cultures.

PMID- 8734643
TI  - Expression of the major inner capsid protein, VP6, of avian rotavirus in
      mammalian cells.
AB  - A gene encoding the major inner capsid protein, VP6, of avian rotavirus was
      inserted into the eukaryotic expression vector pAX-91 under the control of the SR
      alpha promoter and was expressed at a high level in simian COS7 cells. The
      expressed VP6 was indistinguishable in terms of electrophoretic mobility from the
      corresponding protein synthesized in simian MA104 cells infected with avian
      rotavirus. Binding assays with a series of monoclonal antibodies (mAbs) that
      corresponded to four antigenic sites on VP6 of avian rotavirus showed that the
      antigenic characteristics of the expressed product were identical to those of the
      native VP6 of avian rotavirus virions. Fiber-like structures that reacted
      strongly with antiserum against rotavirus were observed in VP6-expressing COS7
      cells. Furthermore, an analysis of the tertiary structure of the expressed VP6
      protein indicated that it adopts a trimeric configuration, similar to that of the
      major inner capsid protein of PO-13 virus. From these results, it appears that
      recombinant VP6 will facilitate studies of the structure and function of
      authentic VP6, an important protein in avian rotavirus.

PMID- 8734644
TI  - Sequence variation of the gC gene among pseudorabies virus strains.
AB  - We have determined the nucleotide sequences of the major glycoprotein C (gC) gene
      of 3 pseudorabies virus (PRV) strains isolated in Japan, the USA, and Northern
      Ireland after gene amplification mediated by a polymerase chain reaction (PCR).
      The nucleotide and deduced amino acid sequence homologies among the strains were
      > 98% and > 97%, respectively. The restriction patterns of the amplified DNA
      fragments generated by restriction endonucleases SalI and SmaI revealed three
      genomic variations among the 15 PRV strains. The Japanese PRV isolates have
      identical restriction fragment patterns and differ from those of the non-Japanese
      isolates examined. Among 3 PRV strains with distinctive genotype each other,
      there is no significant difference in pathogenicity for the ddY mouse.

PMID- 8734645
TI  - The immunodominant proteins of reticuloendotheliosis virus.
AB  - The antigenic profiles of three REV prototype strains, CSV, SNV and REV-T and
      eight Israeli isolates were analysed by SDS-PAGE and immunoblotting with
      convalescent chicken serum, three mAbs, 11A25, 11C237 and 11C100, a rabbit
      antiserum to REV-T whole virus (Cui et al., 1986) and a rabbit antiserum to REV-A
      p30 gag protein (Tsai et al., 1985). Under both reducing (+DTT) and non-reducing
      conditions of SDS-PAGE, a major immunodominant 75-100 kDa band was shared by all
      strains examined. In contrast to the chicken serum that recognized both
      continuous and discontinuous epitopes on the 75-100 kDa band of all the isolates,
      the mAbs and the two rabbit sera behaved otherwise. Only the DTT-resistant
      epitopes on the 75-100 kDa band of REV-T were recognized by the rabbit antisera
      and the mAb 11C237, and only the DTT-labile epitopes of REV-T 75-100 kDa antigen
      were detected by mAb 11C100. The two mAbs 11A25 and 11C237 detected discontinuous
      epitopes of all the strains except SNV, while the rabbit antisera recognized the
      discontinuous epitopes on the 75-100 kDa band of all the 11 strains. The rabbit
      antisera and mAb 11C237 detected additional lower molecular weight proteins and
      the mAb 11C237 also detected three proteins of high molecular weight under non
      reducing conditions only. The p30 antiserum detected the low molecular weight
      proteins demonstrating their gag gene-encoded identity. From these results we
      conclude that the major immunogen of REV is the 75-100 kDa protein that contains
      both continuous and discontinuous epitopes. With this panel of antibodies the
      eight new isolates appeared to belong antigenically to REV subtype 3 (Chen et
      al., 1987).

PMID- 8734646
TI  - Comparison of a commercial ELISA and an immunoperoxidase monolayer assay to
      detect antibodies directed against porcine respiratory and reproductive syndrome
      virus.
AB  - A commercially available enzyme-linked immunosorbent assay (ELISA) for the
      detection of antibodies against porcine respiratory and reproductive syndrome
      virus (PRRSV) was compared to an immunoperoxidase monolayer assay (IPMA). Serum
      samples used were collected from pigs experimentally infected with either the
      American or European antigenic type of PRRSV, and also from piglets born to sows
      that had been experimentally infected with the European antigenic type of PRRSV.
      In addition, three sets of European field sera (n = 275, n = 68, n = 349) were
      tested and evaluated using the IPMA as the gold standard. Results showed that
      both the IPMA and the ELISA were able to detect antibodies against the two
      antigenic types of PRRSV. When sera of experimentally infected pigs were tested,
      the IPMA with homologous antigen detected antibodies 2 to 3 days earlier than the
      ELISA, and was more sensitive in detecting maternal antibodies. The ELISA was
      slightly more sensitive for detecting antibodies against the American type than
      for the European type. When sets of field sera were tested, the relative
      sensitivity of the ELISA ranged between 0.68 and 0.91, and the relative
      specificity ranged between 0.75 and 0.97. However, in two of these sets (n = 275,
      n = 349) we determined that a decrease of the threshold value of ELISA (from 0.4
      to 0.3) increased sensitivity without loss of specificity. We concluded that the
      ELISA is an easy, quick and reliable test to diagnose PRRSV infection in swine
      herds.

PMID- 8734647
TI  - Porcine reproductive and respiratory syndrome virus does not exacerbate
      Mycoplasma hyopneumoniae infection in young pigs.
AB  - The purpose of this study was to determine if Porcine Reproductive and
      Respiratory Syndrome (PRRS) virus infection altered the severity of acute
      Mycoplasma hyopneumoniae (MH) infection in young pigs. Twenty five, 3-week-old
      male pigs were randomly assigned by litter and weight to one of 3 groups. Groups
      1 (PRRS only, n = 5) and 2 (PRRS + MH, n = 10) were inoculated intranasally with
      PRRS virus (IN-5 isolate, 10(5) TCID50) and viremia in all pigs was confirmed by
      virus isolation from serum 3 days later. Group 3 (MH only, n = 10) was inoculated
      at the same time with virus free culture media. Seven days after virus
      inoculation, Groups 2 and 3 were inoculated intratracheally with MH (strain P
      5722-3, 10(7) CCU). All pigs were euthanized and necropsied 28 days later, when
      maximum lesions of mycoplasmosis occurs. Pigs in group 1 did not cough and had no
      gross lung lesions, but were still viremic at necropsy. MH was isolated from all
      pigs in groups 2 (avg. log 5.2 +/- 1.3) and 3 (avg. log 5.1 +/- 1.5), but
      differences were not significant (P = 0.87). Similarly, there were no differences
      in average days coughing (8.9 +/- 2.8 v 11.2 +/- 4.5, P = 0.17), grossly
      pneumonic lung (16.5% v 17%, P = 0.91), or microscopic lung lesion scores (10.1
      +/- 2.6 v 11.1 +/- 1.9, P = 0.35) between pigs in groups 2 and 3. Under these
      experimental conditions, PRRS virus infection did not increase the severity of
      experimental Mycoplasma hyopneumoniae infection in young pigs.

PMID- 8734648
TI  - Sensitivity of Australian isolates of Salmonella enteritidis to nitrofurantoin
      and furazolidone.
AB  - Susceptibility of 66 and 62 Australian isolates of Salmonella enteritidis to
      nitrofurantoin and furazolidone, respectively, was determined. Most isolates were
      susceptible to both antibiotics. Cross-resistance was low among all isolates, but
      higher among the subset of phage type 4 isolates. These results contrast directly
      with those of a previous study (Rampling, A., Upson, R. and Brown, D.F.J. (1990)
      J. Antimicrob. Chemother., 25: 285-290). Sensitivity among Australian isolates of
      S. enteritidis does to some extent, support the contention that furans may have
      played a role in the selection and enhanced colonisation of poultry by Salmonella
      enteritidis in Britain. Furthermore, nitrofurantoin should not be used as a
      selective agent in the isolation of Salmonella enteritidis.

PMID- 8734649
TI  - Disability and handicap in dermatology.

PMID- 8734650
TI  - Photodynamic therapy in dermatology.

PMID- 8734651
TI  - Cutaneous findings in the mentally retarded.

PMID- 8734652
TI  - Chloroquine pruritus: a possible fixed cutaneous reaction.

PMID- 8734653
TI  - Trichohyalin expression in skin tumors: retrieval of trichohyalin antigenicity in
      tissues by microwave irradiation.
AB  - BACKGROUND: The antitrichohyalin antibody AE 15 is effective for identifying the
      cell lineage that undergoes the pathway of inner root sheath-type
      differentiation. Unfortunately, the AE 15 does not react with trichohyalin in
      tissue that is formalin-fixed and embedded in paraffin according to routine
      procedures. METHODS: We attempted to retrieve the trichohyalin antigenicity in
      formalin-fixed, paraffin-embedded biopsy specimens that included normal skin as
      well as skin tumors such as trichofolliculoma and pilotricoma. RESULTS: We found
      that the use of a metal solution in combination with microwave oven heating
      improves the trichohyalin immunoreactivity substantially. Further, trichohyalin
      was found to be expressed not only in the secondary hair structure in
      trichofolliculoma but also in a certain cell lineage that differentiates to
      squamoid cells in pilomatricoma. CONCLUSIONS: Our findings established that
      surgical specimens processed under routine procedures can be successfully
      investigated with AE 15 using the microwave irradiation method. Studies of
      epidermal diseases expressing trichohyalin should provide valuable insights into
      our understanding the functional significance of trichohyalin during abnormal
      keratinization.

PMID- 8734654
TI  - Linear scleroderma in children.
AB  - BACKGROUND: Linear scleroderma is a cutaneous disease of unknown etiology. It
      most often affects children, who develop band-like lesions in an asymmetric
      distribution. The literature is reviewed as to the diagnosis, pathogenesis, and
      treatment of linear scleroderma. CASE REPORT: Six new cases of linear scleroderma
      in children are reported. Their ages ranged from 6 to 17 years, and five were
      girls. A 17-year-old girl had en coup de sabre. Multiple treatment modalities
      were used. All laboratory testing was negative. CONCLUSIONS: Linear scleroderma
      is a clinical diagnosis. The pathogenesis remains unknown. A consistently
      effective therapy has not been found, although diphenylhydantoin and ticlopidine
      hydrochloride should be evaluated in clinical trials.

PMID- 8734655
TI  - Ultrastructure and human papillomavirus DNA in papillomatosis of external
      auditory canal.
AB  - BACKGROUND: A viral etiology has been suspected in papillomatosis of the external
      auditory canal (PEAC), but virus particles have not been detected so far,
      although they are easily demonstrable in skin warts. The purpose of the study was
      to solve this discrepancy by the use of polymerase chain reaction (PCR).
      MATERIALS AND METHODS: Specimens from the external auditory canal of 14 patients
      with PEAC, but no human papilloma virus infection of the genital areas, were
      examined histologically by light and electron microscopy, as well as by PCR to
      detect viral DNA. RESULTS: Histologically, papillomatosis was present in all
      specimens. Vacuolated cells were found in the upper part of the stratum malpighii
      in five cases. On electron microscopy, the numbers of perichromatin and
      interchromatin granules were increased, but no viral granules were observed. In
      all specimens, DNA of HPV 6 was detected using PCR, but there was no evidence of
      DNA of other HPV. CONCLUSIONS: Papilloma of the external auditory canal is
      produced by infection with HPV 6.

PMID- 8734656
TI  - The cost of treating genital warts.
AB  - BACKGROUND: Genital warts is a common sexually transmitted disease treated by a
      variety of medical specialists. Standard therapies offer symptomatic relief but
      cannot ensure lasting remission. Using the clinical literature, claims databases,
      and a panel of experienced practitioners, the relative efficacy, cost, and cost
      effectiveness of five common treatments for genital warts were assessed in this
      study. METHODS: We reviewed the clinical literature for the following genital
      wart therapies: podofilox, podophyllin, trichloroacetic acid, cryotherapy, and
      laser therapy, focusing on their relative efficacy. Physicians experienced in
      treating genital warts defined standard treatment protocols for men and women
      patients with moderate wart burdens. Using national claims data and protocols
      developed by physicians, we derived three economic models based on provider
      charges, third-party payments, and a resource-based relative value scale,
      respectively. RESULTS: The literature review demonstrated highly variable success
      and recurrence rates among treatment methods and failed to show that one
      treatment provides consistently superior efficacy. In the economic models,
      treating women generally proved more costly than treating men per episode of
      care. This was due to the need for more extensive follow-up visits in the
      treatment of women. Total costs were highest for cryotherapy and lowest for a
      patient-applied therapy that reduced the need for follow-up visits. CONCLUSIONS:
      Clinicians should consider both clinical and cost issues when choosing the
      appropriate treatment for patients with genital warts.

PMID- 8734657
TI  - Accessory mammary tissue associated with congenital and hereditary nephrourinary
      malformations.
AB  - BACKGROUND AND OBJECTIVES: The association between polythelia (supernumerary
      nipple) and kidney and urinary tract malformations (KUTM) is controversial. Some
      authors reported this association in newborns and infants. Case-control studies
      dealing with adult subjects are not found in the literature. The purpose of this
      study is to determine the frequency of the association between accessory mammary
      tissue (AMT) and congenital and hereditary nephrourinary defects in an adult
      population compared to a control group. METHODS: The study was performed in 146
      white patients (123 men, 23 women) with AMT out of 2645 subjects consecutively
      referred to us for physical examination. The following investigations were
      undertaken: ultrasonographic examination of the abdomen and the kidneys, ECG,
      echocardiogram, roentgenogram of the vertebral column, urinalysis, and other
      laboratory tests. A sex- and age-matched control group without any evidence of
      AMT or lateral displacement of the nipples underwent the same examinations.
      RESULTS: Kidney and urinary tract malformations were detected in 11 patients with
      AMT (nine men, two women) and in one control. These data indicate a significantly
      higher frequency of KUTM in the AMT-affected patients compared to controls (7.53%
      vs. 0.68%, P < 0.001). A broad spectrum of KUTM was discovered in association
      with AMT: adult dominant polycystic kidney disease, unilateral renal agenesis,
      cystic renal dysplasia, familial renal cysts, and congenital stenosis of the
      pyeloureteral joint. CONCLUSION: Accessory mammary tissue offers an important
      clue for congenital and hereditary anomalies of the kidneys and urinary
      collecting systems. Patients with AMT should, therefore, be extensively examined
      for the presence of occult nephrouropathies.

PMID- 8734658
TI  - Sarcoma of Meckel's cartilage.

PMID- 8734659
TI  - Localized Darier's disease and its nosologic status.

PMID- 8734660
TI  - Generalized lentiginosis manifesting through three generations.

PMID- 8734661
TI  - Bilateral segmental neurofibromatosis with speckled lentiginous nevus.

PMID- 8734662
TI  - Persistently recurring Mediterranean Kaposi's sarcoma on skin grafts.

PMID- 8734663
TI  - Multiple lipomas, angiolipomas, and parathyroid adenomas in a patient with Birt
      Hogg-Dube syndrome.

PMID- 8734664
TI  - Nonpigmenting fixed drug eruption after pseudoephedrine.

PMID- 8734665
TI  - Hyperkeratotic chronic tinea pedis treated with neticonazole cream. Neticonazole
      Study Group.

PMID- 8734666
TI  - Onychomycosis treated with a short course of oral terbinafine.

PMID- 8734667
TI  - The second "sacred disease": earlier euphemistic equivalent of "Hansen's
      disease".

PMID- 8734668
TI  - Erythrodermic psoriasis associated with hyperuricemia and Iatrogenic Cushing's
      syndrome due to topical corticosteroid therapy.

PMID- 8734669
TI  - White House announces cancer-drug initiatives.

PMID- 8734671
TI  - CDC panel develops action plan for drug-resistant streptococci.

PMID- 8734672
TI  - Safety profiles of tramadol, lindane, and astemizole updated.

PMID- 8734673
TI  - Considering a hybrid system for automated drug distribution.

PMID- 8734674
TI  - Effectiveness and safety of once-daily aminoglycosides: a meta-analysis.
AB  - The effectiveness and safety of once-daily versus several-times-daily
      aminoglycosides were studied in a meta-analysis. MEDLINE for 1988 to 1995 was
      searched, and additional studies were identified from review articles and
      references in retrieved articles. Studies selected for meta-analysis were
      randomized controlled clinical trials in nonneutropenic adult patients comparing
      the clinical effectiveness or nephrotoxicity or ototoxicity of once-daily with
      several-times-daily aminoglycosides. Differences between groups were expressed as
      odds ratios. The results were combined by the procedure of Mantel and Haenszel,
      and 95% confidence intervals and exact confidence intervals were computed. An
      odds ratio smaller than 1 would indicate a lesser likelihood of a given endpoint
      in the once-daily group, and an odds ratio greater than 1 would indicate a
      greater likelihood. Eighteen studies involving 2317 patients were included in the
      meta-analysis. Summary odds ratios were 1.47 for effectiveness (95% CI = 1.13
      1.94), 0.56 for ototoxicity (95% CI = 0.26-1.16), and 0.60 for nephrotoxicity
      (95% CI = 0.40-0.86). A meta-analysis showed that treatment with single daily
      doses of aminoglycosides seems to be more effective, less nephrotoxic, and as
      ototoxic as multiple doses daily.

PMID- 8734675
TI  - Establishing an outpatient anticoagulation clinic in a community hospital.
AB  - The establishment of a pharmacist-managed out-patient anticoagulation clinic in a
      private community hospital is described. Discussions by pharmacy with office
      based physicians at a 187-bed, private, nonprofit community medical center
      indicated that the traditional system of anticoagulation management was not ideal
      for the physicians or their patients. Development of a pharmacist-managed
      anticoagulation clinic began in fall 1993; operations began in spring 1994.
      Planning included analyzing existing practices, reviewing the relevant
      literature, obtaining physician input, visiting an established anticoagulation
      clinic, formulating a business plan, and developing clinical protocols.
      Collaborative relationships were established with the hospital laboratory,
      business office, and risk management, information services, and medical records
      departments. Two pharmacists were trained to work in the clinic and provide
      coverage 24 hours a day. Services include patient assessment, monitoring of
      anticoagulation, warfarin dosage adjustment, medication management, patient
      education, follow-up care, and providing feedback to referring and attending
      physicians. The clinic has met with physician and patient satisfaction, has
      reduced the number of admissions to treat warfarin-related bleeding, and has been
      able to cover its direct costs. A pharmacist-managed anti-coagulation clinic was
      successfully established in a private community hospital.

PMID- 8734676
TI  - Stability of an extemporaneously compounded levothyroxine sodium oral liquid.
AB  - The stability of levothyroxine sodium in oral liquid dosage forms compounded from
      commercially available tablets was studied. Levothyroxine sodium oral liquids (25
      micrograms/mL) were prepared from tablets and from powder with and without
      methylparaben preservative and transferred to amber, high-density polyethylene
      bottles. Five bottles of each tablet-based formulation were stored at 2-8 degrees
      C, 23-27 degrees C, and 38-42 degrees C, and five bottles of each powder-based
      formulation were stored at 38-42 degrees C. On days 3, 8, 14, 22, 31, 61, and 90,
      samples were taken from each bottle and analyzed for drug concentration by
      stability-indicating high-performance liquid chromatography. There was
      significant degradation of levothyroxine sodium in all the formulations. However,
      the tablet-based formulation without preservative stored at 4 degrees C retained
      at least 90% of its initial concentration for eight days after compounding.
      Degradation occurred faster in the tablet-based formulation with preservative.
      None of the formulations retained > or = 90% initial potency by day 14. An
      extemporaneous oral liquid formulation of levothyroxine sodium 25 micrograms/mL
      compounded from crushed tablets was stable for eight days when stored in amber
      bottles at 4 degrees C.

PMID- 8734677
TI  - Improving the presentation of drug information to pharmacy and therapeutics
      committees for formulary decisions.

PMID- 8734678
TI  - Weight-based protocol for improving heparin therapy.

PMID- 8734679
TI  - Accuracy and reproducibility of syringe measurements.

PMID- 8734680
TI  - Effect of autoclaving on stability of nitrofurazone soluble dressing.

PMID- 8734681
TI  - Stability of doxorubicin hydrochloride and vincristine sulfate in two portable
      infusion-pump reservoirs.

PMID- 8734682
TI  - Stability of granisetron hydrochloride with dexamethasone sodium phosphate for 14
      days.

PMID- 8734683
TI  - ASHP's development of patient-education programs.
AB  - On February 14 and 15, 1996, FDA sponsored a public meeting and workshop to
      elicit recommendations on providing written educational material that patients
      would find useful (see April 1, 1996, AJHP, page 712). To learn more about
      systems that generate patient information, particularly information that is drug
      specific, FDA invited companies that produce these systems to explain their
      approaches. Representatives from ASHP, USP, Medical Economics, Medi-Span, and
      First DataBank provided meeting attendees with overviews of their products. ASHP
      Senior Vice President Mary Jo Reilly presented the ASHP products Medication
      Teaching Manual and MedTeach and explained the Society's history of encouraging
      pharmacists to provide patients with useful information.

PMID- 8734684
TI  - Criteria for use of valproate in adult psychiatric inpatients and outpatients.

PMID- 8734685
TI  - Mitoxantrone extravasation and tissue necrosis.

PMID- 8734686
TI  - Wrong information in computerized drug monograph.

PMID- 8734687
TI  - Need for quality-control testing of extemporaneously prepared oral solids.

PMID- 8734688
TI  - Error in epoprostenol package labeling.

PMID- 8734689
TI  - Assembling a performance improvement committee before Joint Commission
      evaluation.

PMID- 8734690
TI  - Importance of public health in the next century.

PMID- 8734692
TI  - Dental care of patients who receive head and neck radiation therapy.

PMID- 8734693
TI  - Buccinator flap for closure of large palatal defects.

PMID- 8734694
TI  - Long-term follow-up of modified condylotomy for internal derangement of the
      temporomandibular joint.
AB  - OBJECTIVES: The purpose of this study was to evaluate disk position and patient
      response 10 years after modified condylotomy for symptomatic reducing disk
      displacement. STUDY DESIGNS: Questionnaires and invitations to return for
      examination and temporomandibular joint magnetic resonance imaging were mailed to
      39 consecutive patients 10 years after modified condylotomy. RESULTS: On a 10
      point scale the mean pain experienced by the 17 respondents (27 joints) to the
      questionnaire was 2.0. Ninety percent of 20 joints (12 patients) examined were
      free of tenderness to palpation. Magnetic resonance imaging in 10 patients (17
      joints) showed disk reduction in 59%, displacement with reduction in 29%, and
      displacement without reduction in 12%. Eighty-five percent of the joints met
      American Association of Oral and Maxillofacial surgeons criteria for a successful
      therapeutic outcome. CONCLUSIONS: The study suggests a role for modified
      condylotomy in the long-term management of symptoms associated with reducing disk
      displacement. Further, modified condylotomy can frequently reverse an internal
      derangement and seems to protect against the natural progression of
      osteoarthrosis.

PMID- 8734695
TI  - Electromyographic and kinesiographic study in patients with nonreducing disk
      displacement of the temporomandibular joint.
AB  - OBJECTIVE: The purpose of this study was to clarify electromyographic and
      mandibular kinesiographic properties of the chewing movements in patients with
      unilaterally painful nonreducing disk displacement of the temporomandibular
      joint. STUDY DESIGN: Chewing movement in 50 female patients was evaluated by
      electromyograph and mandibular kinesiograph, and the results were compared with
      those in 31 normal controls. RESULTS: In the analysis by electromyograph, some
      differences between patients and controls were found. In the analysis by
      mandibular kinesiograph, chewing movement showed deviation to the chewing side in
      the TMJ-affected-side chewing but did not show deviation in the TMJ-unaffected
      side chewing in the horizontal plane. The maximal anteroposterior width between
      opening and closing paths in the sagittal plane was smaller in the experimental
      subjects. CONCLUSION: These differences between patients and controls may be
      helpful to diagnosis for painful nonreducing disk displacement of the
      temporomandibular joint.

PMID- 8734696
TI  - Supratarsal fold incision for approach to the superior lateral orbit.
AB  - OBJECTIVE: To report and evaluate the use of the supratarsal fold incision for
      access to the lateral and superior orbit. DESIGN: This is a retrospective
      evaluation of seven patients with zygomatic and orbital fractures who underwent
      repair with the supratarsal fold incision used to expose the frontozygomatic
      region or supraorbital rim. Data were obtained by review of hospital charts,
      radiographs, and by clinical examination. RESULTS: Excellent exposure and access
      were obtained because of the proximity of the incision to the lateral and
      superior orbit. Mobility of the eyelid tissue allowed for atraumatic manipulation
      and retraction. All fractures were adequately reduced by clinical and
      radiographic examination without complication. CONCLUSION: The supratarsal fold
      incision is a versatile incision for access to the zygomaticofrontal suture and
      supraorbital rim. In addition to providing excellent exposure, it produces a
      superb cosmetic result with a scar well-hidden in the skin folds of the upper
      eyelid.

PMID- 8734697
TI  - Pericoronitis and tonsillitis: clinical and darkfield microscopy findings.
AB  - OBJECTIVE: Upper respiratory tract infections and tonsillitis and pharyngitis in
      particular increase the risk of lower third molar pericoronitis. The study was
      made to investigate clinical and microbiologic associations between pericoronitis
      and tonsillitis. STUDY DESIGN: The subjects were 20-year-old Finnish male
      conscripts. Thirty-eight patients had tonsillitis without and 33 patients had
      tonsillitis with a symptom-free erupting lower third molar; 27 patients had
      pericoronitis but healthy tonsils. All subjects were examined clinically.
      Bacterial samples were taken from healthy and diseased tonsils and from healthy
      and diseased third molar pericoronal pockets. The microbes were classified
      morphologically with the use of a darkfield microscope. RESULTS: Eighty-two
      percent of infected tonsils had deep crypts and 52% of them exudated pus compared
      with 36% (p < 0.001) and 0% (p < 0.001) in healthy tonsils, respectively.
      Infected lower third molars were less than half erupted and had on average 8.8 mm
      deep pericoronal pockets compared with pockets 5.5 mm deep recorded in symptom
      free cases (p < 0.001). Spirochetes were more common in infected pockets than in
      symptom-free cases comprising 8.2% versus 3.0% of the total bacterial count (p =
      0.044). Rods were more common in infected tonsils than healthy ones (8.9% versus
      4.8%, p = 0.041). CONCLUSION: There were similarities in morphologic microbiota
      of pericoronitis and tonsillitis. However, clinical findings of tonsils did not
      appear to link with the findings of third molars.

PMID- 8734698
TI  - Nonsurgical treatment of patients with periodontal disease.
AB  - OBJECTIVE: To determine whether the short-term use of systemic antimicrobials
      (metronidazole or doxycycline) and locally delivered antimicrobials
      (metronidazole, chlorhexidine) in patients with advanced forms of periodontal
      disease could prevent the normally necessary access surgery. STUDY DESIGN: Ninety
      four patients were randomly assigned with the use of a double-blind protocol.
      RESULTS: There was a 93% reduction in the need for periodontal surgery about
      individual teeth and an 81% reduction in the need for tooth extractions. Only 93
      teeth of an initial total of 783 teeth actually needed surgery or extractions.
      Eighty-one percent of the patients entered into the maintenance phase of
      treatment without needing surgical treatments. CONCLUSION: These findings
      indicate that a treatment paradigm based on the diagnosis and treatment of
      anaerobic infections is likely to be successful in those patients for whom access
      surgery is recommended.

PMID- 8734699
TI  - Masticatory muscle symptoms in a patient with McArdle's disease.
AB  - Myofascial pain dysfunction syndrome is a syndrome characterized by chronic
      preauricular pain and tenderness involving the muscles of mastication. The cause
      is often multifaceted and generally poorly defined. A case of McArdle's disease
      is discussed in which the patient presented with symptoms consistent with
      myofascial pain dysfunction syndrome. McArdle's disease is a rare autosomal
      recessive glycogen storage disorder in which there is a metabolic myopathy that
      results in exercise intolerance, muscle pain, and tenderness, and that in this
      patient gave rise to chronic symptoms of myofascial pain. Although uncommon,
      McArdle's disease should be considered in the diagnosis of patients with symptoms
      of myofascial pain dysfunction syndrome because the condition has important
      implications with respect to the patients renal function and because it can be
      readily distinguished by simple investigations.

PMID- 8734700
TI  - Diagnosis of acute bone/bone marrow infarction of the mandible in sickle
      hemoglobinopathy. Report of a case.
AB  - Vasoocclusive involvement of bones is a common cause of acute morbidity in
      patients with sickle cell hemoglobinopathy. Although the literature contains only
      two reports of infarction of the mandible in sickle cell vasooccusive crisis,
      earlier authors were often limited to the clinical examination as their primary
      or only diagnostic method. This article presents a sickle cell patient in
      vasoocclusive crisis who subsequently developed infarction of the right mandible
      without an infectious or inflammatory cause and was ultimately diagnosed by
      nuclear bone imaging scans.

PMID- 8734701
TI  - Oral manifestations of severe short-limb dwarfism resembling Grebe
      chondrodysplasia: report of a case.
AB  - The oral and dental abnormalities associated with a distinct variety of severe
      short-limb dwarfism are described. The patient, a 9-year-old Arab boy, had
      delayed development and eruption of teeth, severe oligodontia of permanent
      dentition, hypodontia, microdontia, supplemental incisor, enamel hypoplasia of
      primary teeth, doubled and abnormal frenal attachments, bifid uvula, hypoplastic
      maxilla, and malocclusion. Clinical and radiographic examinations revealed
      asymmetric dysplasia and anaplasia of long bones, craniofacial dysmorphia,
      prominent forehead, budlike fingers and bulbous toes, dysplastic nails, severe
      hearing loss, and reduced joint mobility. These features resemble, in general,
      those characteristic of Grebe chondrodysplasia, an extremely rare ill-defined
      syndrome that is inherited as an autosomal-recessive disorder.

PMID- 8734702
TI  - Thrombophilia, hypofibrinolysis, and alveolar osteonecrosis of the jaws.
AB  - OBJECTIVES: Our specific aim in 49 patients (42 women, 7 men) with osteonecrosis
      of the jaw was to determine whether thrombophilia (increased tendency to
      intravascular thrombosis) or hypofibrinolysis (reduced ability to lyse thrombi)
      were associated with this regional avascular necrosis. STUDY DESIGN: Determinants
      of thrombosis and fibrinolysis were compared in healthy controls and in 42 women
      and 7 men who had biopsy-proven idiopathic osteonecrosis of the jaw with severe
      chronic jaw or facial pain syndromes and failure to respond to conventional
      medical and dental treatments. RESULTS: Of the 49 patients, 35 (71%) had
      thrombophilia or hypofibrinolysis and only 14 were normal. Thrombophilia as a
      sole coagulation defect was found in 10 patients, 7 with resistance to activated
      protein C and 3 with low protein C (deficiency of an antithrombotic protein).
      Hypofibrinolysis with low stimulated tissue plasminogen activator activity and
      high lipoprotein (a) (an atherogenic, hypofibrinolytic lipoprotein) were found as
      sole coagulation defects in seven and eight patients, respectively. Ten patients
      had mixed defects; 7 of these 10 had thrombophilia with resistance to activated
      protein C. Sinusoidal dilatation was a constant feature in maxillary and
      mandibular bone biopsies, suggesting venous occlusion with intramedullary
      hypertension. Marrow fibrosis and occasional fibrin plugs were additional
      microscopic features believed to impair venous drainage and to contribute to
      ischemic necrosis of the alveolar bone. CONCLUSIONS: Primary thrombophilia and
      hypofibrinolysis appear to be common, heritable, pathophysiologic risk factors
      for idiopathic osteonecrosis of the jaws. These coagulation defects may also
      contribute to alveolar neuralgia, atypical odontalgia and facial neuralgia,
      idiopathic trigeminal neuralgia, and to treatment failures so often encountered
      in patients with alveolar osteonecrosis and disabling chronic facial and jawbone
      pain syndromes.

PMID- 8734704
TI  - Focal myositis of the floor of mouth: report of two cases and review of the
      literature.
AB  - Focal myositis is an uncommon inflammatory myopathy of unknown cause affecting
      skeletal muscle. It may be mistaken on clinical evaluation for a malignant
      neoplasm. We describe two cases, both involving the mylohyoid muscle of the floor
      of the mouth. In each case excisional biopsy of a firm indurated mass revealed a
      focal lymphocytic and histiocytic infiltrate associated with degenerating and
      regenerating skeletal muscle fibers. No clinical or biochemical evidence of
      generalized muscle disease was seen at presentation or at 1-year and 7-year
      follow-up examination. The literature on focal myositis involving the head and
      neck region is reviewed.

PMID- 8734703
TI  - Scanning electron microscopy of teeth in osteogenesis imperfecta type I.
AB  - Opalescent teeth from five patients and nonopalescent teeth from six patients
      with osteogenesis imperfecta type I were examined with the scanning electron
      microscope and their appearances compared with those of teeth from normal
      persons. In opalescent teeth the main findings were a reduction in the number and
      variation in the size of the dentinal tubules that were irregularly embedded
      within the disturbed dentinal matrix and an abnormally smooth enamel-dentinal
      junction. Similar less marked dentinal abnormalities were found in the
      nonopalescent teeth from three patients. No abnormality was found in the enamel
      in any of the teeth examined. These findings suggest that in osteogenesis
      imperfecta teeth that appear normal may have defective dentine. This relevant to
      the current clinical classification of the disorder into subgroups according to
      the clinical presence or absence of affected teeth.

PMID- 8734705
TI  - Heterotopic gastrointestinal and pancreatic tissue of the tongue: a case report.
AB  - Heterotopic gastrointestinal mucosa of the tongue is a rare type of oral
      choristoma. Associated pancreatic tissue has never been reported to our
      knowledge. We present the case of an 8-month-old female infant with congenital
      cleft palate who had a tongue mass. On histologic evaluation the lesion consisted
      of gastrointestinal and pancreatic tissue. This choristoma may arise from
      entrapped multipotential endoderm during tongue development.

PMID- 8734706
TI  - Metastatic renal cell carcinoma involving Wharton's duct: a case report.
AB  - This article describes a case of renal cell carcinoma that metastasized to the
      right Wharton's duct of a 73-year-old man. Metastases of renal cell carcinoma to
      the oral tissues are rare. Involvement of salivary gland tissue appears to be
      exceedingly rare, and a metastatic focus localized only in the Wharton's duct
      never has been reported in the literature.

PMID- 8734707
TI  - Hyperplasia of the sublingual glands in adult patients.
AB  - Hyperplasia of the sublingual salivary glands in an entity of unknown cause not
      previously reported in the literature. The main clinical finding is a unilateral
      or bilateral painless sublingual enlargement of the sublingual gland without any
      recognized local or systemic associated factor.

PMID- 8734708
TI  - Chondroid lipoma. A newly described lesion that may be mistaken for malignancy.
AB  - A case of chondroid lipoma located in the submandibular region of a 21-year-old
      man is presented. On macroscopic evaluation the tumor was lobulated and quite
      yellow. Microscopic examination showed that this tumor was composed of mature
      adipose tissue and eosinophilic cells. The eosinophilic cells displayed single or
      multiple vacuoles and resembled lipoblast or hibernoma-like cells. These were set
      in a myxoid or chondromyxoid stroma. Most cells reacted with antibodies directed
      against vimentin and neuron-specific enolase. Focal weak positivity for S-100
      protein was noted. Principal considerations in the histopathologic differential
      diagnosis included hibernoma, myxoid liposarcoma, and extraskeletal myxoid
      chondrosarcoma (chordoid sarcoma).

PMID- 8734709
TI  - Penicillin as a supplement in resolving the localized acute apical abscess.
AB  - PROBLEM: Antibiotics are often prescribed indiscriminately to treat endodontic
      emergencies. OBJECTIVES: This study examined (1) the effect of penicillin
      supplementation on reduction of symptoms and (2) the course of recovery of
      localized acute apical abscess after emergency treatment. STUDY DESIGN: Patients
      with pulp necrosis and periapical pain and/or localized swelling were considered.
      Those eligible did not have any signs of spreading infections. Patients received
      appropriate local treatment, and a double-blind protocol was used to randomly
      assign them to one of three groups: penicillin VK group, placebo group, or
      neither medication group. All received ibuprofen 600 mg four times daily for 24
      hours. Patients entered their pre- and postoperative pain and swelling experience
      on a visual analog scale for up to 72 hours. RESULTS: Resolution was fairly rapid
      in most patients. Statistical analysis of the scores of 32 respondents revealed
      no significant differences (at p < 0.05) between the three groups in course of
      recovery or symptoms at any time period. CONCLUSIONS: Patients with localized
      periapical pain or swelling generally recovered quickly with local treatment. The
      data did not show a demonstrable benefit from penicillin supplementation.

PMID- 8734710
TI  - Machining efficiency and wear resistance of nickel-titanium endodontic files.
AB  - OBJECTIVE: Nickel-titanium endodontic files are more flexible than stainless
      steel. Little information is reported concerning machining efficiency and wear
      resistance of nickel titanium. This study assessed the dentin-machining ability
      and wear resistance of nickel titanium endodontic files in vitro. STUDY DESIGN:
      The method described earlier to assess machining efficiency and wear resistance
      of stainless steel files was used. Eight different types and brands of nickel
      titanium files were studied: Ultra-Flex Hedstrom, Ultra-Flex K, Mity Hedstrom,
      Mity K, Mity Turbo, Hedstrom Naviflex NT, NiTiFlex, and Hyflex X-file. Thirty
      files of each brand were evaluated. One-way ANOVA and t tests were performed to
      analyze the data. RESULTS: Considerable variation was found in matching
      efficiency and wear. The best initial machining ability of all nickel titanium
      instruments was recorded for the Hyflex-X file (0.60 +/- 0.16 mm2); the poorest
      performance was for the Mity Turbo file, which machined less than one third of
      the best performing instrument (0.19 +/- 0.12 mm2). CONCLUSIONS: We compared our
      results with results of a previous study of stainless steel endodontic files and
      concluded that nickel titanium instruments are as aggressive as or better than
      stainless steel instruments in removing dentin. They are also more durable than
      their stainless steel counterparts.

PMID- 8734711
TI  - Radiology: closing a century, opening a millennium.
AB  - As we close the file on the first century of radiology, we honor the pioneers and
      reflect on the progress they started. We also open a new file, not just a new
      century, but a new millennium of opportunity. The dramatic technologic advances
      in diagnostic imaging within recent decades have provided the foundation for
      expanding our activities in Oral and Maxillofacial Radiology. We are no longer
      just dental radiology; we can no longer rest on the teaching and practice of
      conventional dental radiography. We can summarize in one word the direction our
      efforts must take in opening the millennium: research. Only with research at the
      fundamental as well as clinical level we can continue to expand our service to
      the public, to our patients, and to our colleagues.

PMID- 8734712
TI  - Dose reduction of two digital sensor systems measuring file lengths.
AB  - OBJECTIVE: The aim of this study was to determine the effect of dose reduction on
      the image quality of two sensor systems with automatic greyscale adjustment.
      STUDY DESIGN: Two digital sensor systems, Sidexis (Siemens, Bensheim, Germany)
      and Digora (Soredex, Helsinki, Finland), were tested. The image quality of the
      systems was determined by comparing lengths of endodontic files (025, 020, 015,
      and 010 files) and a premolar root in the digital images with lengths on
      conventional radiographic films. For the experiments the exposure was changed to
      100%, 50%, 25%, 12.5%, 6.25%, and 3.125% of that for Ektaspeed films. RESULTS:
      The lengths of 025 and 020 files and the premolar root in the digital images were
      comparable with the lengths on films even if the exposure was reduced to 6% of
      that used for Ektaspeed films. The lengths of 015 files reduced as the exposure
      was reduced. The lengths of 010 files were significantly shorter than the lengths
      on films. CONCLUSIONS: With the systems tested, a dose reduction of approximately
      95% compared with Ektaspeed films is possible to determine the lengths of a
      premolar root and 025 and 020 files. For thinner objects a dose reduction is
      questionable.

PMID- 8734713
TI  - Radiographic changes in the temporomandibular joint in patients with generalized
      osteoarthritis and rheumatoid arthritis.
AB  - This is the first study concerned with radiographic characteristics in patients
      with generalized osteoarthritis and signs and symptoms of temporomandibular joint
      involvement. For comparison, patients with rheumatoid arthritis and
      temporomandibular joint involvement were used. The patient material comprised 20
      patients with generalized osteoarthritis (20 joints) and 21 patients with
      rheumatoid arthritis (21 joints). The radiographic methods were corrected
      sagittal tomography (hard tissue changes, joint space, and condylar position),
      frontal tomography (hard tissue changes), and individualized oblique lateral
      transcranial projections (condylar translation). Sixteen (80%) joints in the
      group of patients with generalized osteoarthritis and 15 (71%) joints in the
      group with rheumatoid arthritis revealed structural changes. The condyle was the
      predominant location. No radiographic criterion was pathognomonic for generalized
      osteoarthritis or rheumatoid arthritis. However, osteophytes, flattening of the
      condyle, or a reduced joint space was observed more often in joints with
      generalized osteoarthritis, whereas erosions in the condyle were more common in
      joints with rheumatoid arthritis. The radiographic findings in patients with
      generalized osteoarthritis are more similar to those seen in patients who have
      the common form of temporomandibular joint osteoarthritis than to those in
      patients with rheumatoid arthritis.

PMID- 8734714
TI  - Three-dimensional computed tomography reconstruction in treatment planning for
      large ameloblastoma.
AB  - A case of an unusually large mandibular ameloblastoma is reported in which
      standard radiologic examination failed to provide adequate visualization of the
      tumor's limits because of overlapping structures and the presence of compound
      shadows. Computed tomography imaging and three-dimensional reconstruction proved
      invaluable in the treatment planning of this large lesion, because it allowed the
      surgeon to visualize and comprehend the geography of the tumor and its
      relationship to surrounding structures and soft tissues and to formulate a
      surgical plan. Use of this technique helped ensure complete excision of the tumor
      without excessive removal of uninvolved tissue.

PMID- 8734715
TI  - Cherubism: diagnostic imaging and review of the literature in Japan.
AB  - Cherubism is a nonneoplastic disease of bone characterized by clinical,
      bilateral, painless enlargements of the jaws that are said to give the patient a
      cherubic appearance. Cherubism may appear in solitary cases or in many members of
      the family, often in multiple generations. On radiography the lesions have the
      appearance of bilateral multilocular radiolucent areas. On histopathologic
      evaluation the lesions show proliferating fibrous connective tissue containing
      numerous multinucleated giant cells. Since it was first described by Jones in
      1933, many cases have been documented without restriction to any one country or
      ethnic group, but only a few cases have been reported in Japan, apparently
      because it is rare here. We report a case of cherubism in a 15-year-old boy and
      review the Japanese literature.

PMID- 8734716
TI  - Acute obstructive sleep apnea as a complication of sphincter pharyngoplasty.
AB  - This report describes postoperative airway compromise following sphincter
      pharyngoplasty (SP) for treatment of post-palatoplasty velopharyngeal
      dysfunction. A retrospective review of 58 SPs performed for post-palatoplasty
      velopharyngeal dysfunction, on 30 male, and 28 female patients, over a 5-year
      study period was undertaken at a tertiary referral academic institution
      (Washington University School of Medicine), at the St. Louis Children's Hospital,
      Cleft Palate and Craniofacial Deformities Institute. Eight patients were
      identified who had the following inclusion criteria: overt perioperative and/or
      postoperative airway dysfunction, identifiable syndromes, or microretrognathia.
      Items reviewed were patient demographic factors, associated medical problems,
      genetics evaluations, nasendoscopic characteristics of velopharyngeal closure,
      anesthetic evaluation of the patients, and the incidence and severity of
      perioperative complications. Particular attention was paid to factors
      contributing to the airway obstruction. Of the eight subjects with perioperative
      and/or postoperative upper airway dysfunction following SP, five patients had
      Pierre Robin sequence/micrognathia, while three patients had a history of
      perinatal respiratory and/or feeding difficulties without micrognathia or an
      identified genetic disorder. All but two episodes of airway dysfunction resolved
      within 3 days postoperatively. These patients were discharged home with apnea
      monitors; both were readmitted with recurrent airway dysfunction. Continuous
      positive airway pressure (CPAP) was utilized successfully in all instances, and
      no patients required take-down of the SP to relieve airway dysfunction. CPAP is
      an effective, noninvasive treatment strategy for management of iatrogenically
      induced apnea following SP, without sacrificing the surgical benefit of improved
      speech intelligibility.

PMID- 8734717
TI  - Orbital dysmorphology in unilateral coronal synostosis.
AB  - Unilateral coronal synostosis (UCS) produces overt craniofacial dysmorphology.
      UCS surgery in infancy aims to release the osseous restriction and normalize the
      fronto-orbital deformity. The quantitative effect of this surgery on the orbit
      and its contents is unknown. This study was conducted to quantify the
      preoperative orbital dysmorphology and its surgical outcome in patients with
      unilateral coronal synostosis. Twenty-eight UCS patients had preoperative three
      dimensional computerized tomographic (CT) scans (at mean age 4.0 months), cranio
      orbital reconstructive surgery (at 4.7 months), and postoperative scans (at 18.1
      months). The CT data were analyzed using a computer workstation and AnalyzeTM
      biomedical imaging software. Four measurements were performed on both ipsilateral
      (same side as synostosis) and contralateral (opposite to synostosis) orbits of
      each scan: orbital index (OI, 100 x height/width of orbit), orbital cavity volume
      (OV), ocular globe volume (GV), and ventral globe Index (VGI, 100 x globe volume
      ventral to the anterior surface of orbital cavity/GV). The data were analyzed for
      statistical significance using Student's ttest. Preoperatively, the OI was
      significantly greater on the ipsilateral than on the contralateral side (113.7
      vs. 87.3). There was a significant improvement on both sides of the orbit
      postoperatively, with ipsilateral 99.1 and contralateral 92.1. However, the
      difference between both sides remained significant. The OV was smaller in the
      ipsilateral orbits both pre- and postoperatively, with ipse/contralateral ratios
      of 95.8 and 95.2, respectively. Importantly, the GV was consistently smaller in
      the ipsilateral orbits preoperatively, with an ipse/contralateral ratio of 93.3.
      The ratio increased to 97.1 postoperatively, a statistically significant change.
      In the ipsilateral orbits, the preoperative VGI was significantly greater. The
      VGI improved postoperatively. These data indicate that UCS affects the
      development of the osseous orbit as well as its soft-tissue contents. After
      cranio-orbital surgery, there is diminution of asymmetry of both the bony orbit
      and its soft-tissue contents. Partial normalization of orbital dysmorphology
      occurred during the first postoperative year. UCS surgery in infancy does not
      prevent growth of orbital hard or soft tissues, and it seems to permit
      normalization of previously impaired growth.

PMID- 8734718
TI  - Teaching model for closure of oronasal fistula and bone grafting of the maxilla.
AB  - Secondary bone grafting of the maxilla and closure of the residual oronasal
      fistula at the stage of transitional dentition has become a well-accepted
      treatment modality. This procedure, in conjunction with orthodontic treatment,
      has been incorporated into the management protocol of many cleft teams around the
      world in an effort to further improve functional and esthetic habilitation of
      patients with unilateral or bilateral clefts of the lip, alveolus, and palate.

PMID- 8734719
TI  - Extradural deadspace after infant fronto-orbital advancement in Apert syndrome.
AB  - Infant fronto-orbital advancement is presently a management cornerstone of the
      craniosynostosis in Apert syndrome. This procedure is based on the premise that
      the expanding brain rapidly advances in support of, and to remodel, the new
      frontal facade. This series of infant patients with Apert syndrome undergoing
      fronto-orbital advancement with early postoperative computerized tomography
      assessment reveals a large extradural deadspace persistent through the first
      postoperative week, not obliterated consistently until the fourth week. Early
      deadspace effacement results from expansion of the prefrontal subarachnoid space,
      without any significant change in size or shape of the frontal brain substance or
      ventricles. Brain growth or expansion was particularly slow with brain shape
      distortions still evident at late follow-up.

PMID- 8734720
TI  - Fourier analysis of cephalometric shapes.
AB  - Craniofacial growth and development involve both size and shape variations. Shape
      variations can be assessed independently from size using mathematical methods
      such as the Fourier series. A method for the reconstruction of outlines starting
      from selected landmarks and for their Fourier analysis has been developed and
      applied to analyze the age differences in shape in the tracings of the Bolton
      standards (lateral view) from 1 to 18 years of age. The size-independent shape of
      the Bolton standard at 18 years was larger at the chin, at the gonion, and in the
      anterior cranial base than the shape at 1 year of age. Conversely, the younger
      shape was larger in the middle part of face, corresponding roughly to the
      maxillary bone, than the older shape. When standardized for size, growth thus
      seemed to modify craniofacial shape with progressive lengthening and narrowing.
      This shape effect was largely overwhelmed by the very evident size increments,
      and it could be measured only using the proper mathematical methods.

PMID- 8734721
TI  - Proprioceptive representation of the levator veli palatini muscle in the solitary
      nucleus of the rat.
AB  - The levator veli palatini muscle is innervated by motoneurons of the
      glossopharyngeal nerve, which are located within the ambiguus nucleus; however,
      little is known about the afferent fibers of this muscle. A horseradish
      peroxidase study was conducted in rats following injection into the levator veli
      palatini muscle branch to reveal the location and the distribution of dendrites
      of the afferent fibers of the muscle. Terminal labels were densely distributed in
      the lateral region of the solitary nucleus, which receives afferents of the
      glossopharyngeal nerve, ipsilateral and contralateral to the injection site. The
      relationship of the levator veli palatini muscle with respiration was suggested
      by the localization of labeled terminals at sites where the afferents from the
      respiratory organs project densely, and by the demonstrated proprioceptive role
      of the afferent fibers passing through the muscle spindles contained in the
      levator veli palatini muscle.

PMID- 8734722
TI  - Position of upper permanent central incisors prior to eruption in unilateral
      cleft lip and palate.
AB  - The position and degree of eruption of permanent central incisors within the
      premaxilla were measured on x-ray films obtained in 102 patients with unilateral
      cleft lip and palate and in 52 normal individuals aged 5 years. The patients were
      subdivided according to sex and to the method of surgical repair (bone grafting
      or periosteal flap surgery). Individuals with rotated incisors were assessed
      separately. The results showed that maxillary depth was not significantly reduced
      prior to palate surgery while the alveolar process was markedly retroclined. An
      unerupted central upper incisor on the side of the cleft was situated more
      anteriorly than in controls. Because of the distortion of the alveolar process,
      it was retroclined and produced a deformation of the subspinal concavity. Both
      this deformation and the distortion of the alveolar process interfered with the
      measurements of maxillary depth and rendered it inadequate. The incisor on the
      normal side was situated more posteriorly than in controls and was less
      retroclined than the incisor on the affected side. The degree of eruption of
      incisors on both the normal and affected sides did not differ from controls. The
      type of surgical repair influenced only the retroclination of the alveolar
      process and of the incisors within this process. The retroclination was more
      marked after primary bone grafting than after periosteal flap surgery. The
      position and degree of eruption of rotated incisors did not differ from
      nonrotated incisors, and the presence of rotated incisors was not related to the
      degree of the shortening of maxillary depth. There were no significant
      differences between males and females.

PMID- 8734723
TI  - Effect of cuspid positioning in the cleft at the time of secondary alveolar bone
      grafting on eventual graft success.
AB  - This investigation was to determine the relationship between the success of
      secondary alveolar bone grafting and the position of the permanent cuspid
      relative to the cleft at the time of grafting. In this retrospective study
      utilizing periapical radiographs take on cleft patients to evaluate bone grafting
      results, the subjects were patients treated at the Lancaster Cleft Palate Clinic,
      a private institution specializing in the care of cleft patients. Sixty-seven
      patients (20 BCLP; 47 UCLP) were selected for this study based on availability of
      quality radiographs and a minimum of 6-month post-surgical follow-up. All
      patients underwent alveolar bone grafting (mean age, 10 years 7 months).
      Presurgical radiographs were taken within 3 months of the operation. Post
      surgical radiographs were taken to evaluate the outcome of grafting (mean follow
      up, 2 years 10 months). Radiographs were traced and digitized on a total of 86
      cleft sites. Presurgically, a ratio was used to determine the amount of cuspid
      crown emerged through the alveolus into the cleft site relative to the anatomic
      cuspid-crown length. Post-surgically, ratios of bone support for the teeth mesial
      and distal to the cleft were established by dividing the amount of root covered
      by bone by the anatomic root length. Ratios expressing the height of alveolar
      crest relative to the cementoenamel junction (CEJ) of adjacent teeth and amount
      of alveolar notching relative to the mesial tooth root length were also
      evaluated. Linear regressions of each of the five ratios of graft outcome on the
      cuspid-eruption ratio were done. No significant correlations could be found
      between final graft success and the amount of cuspid crown exposed in the cleft
      at the time of grafting. Cuspid position could not be shown to be a significant
      factor in determining graft success.

PMID- 8734724
TI  - Dyspnea following experimentally induced increased nasal airway resistance.
AB  - Nasal resistance (NRZ) values for healthy adults range from 1.0 to 3.5 cm
      H2O/L/sec. Some oral breathing tends to occur at values above 3.5. The purpose of
      the present study was to determine at what level of NRZ individuals sense that
      nasal breathing is difficult. A diaphragm was used to add four different
      resistance loads in random to 15 adult subjects. These loads were 5,8, and 15 cm
      H2O/L/sec and a value 40% above the individual's normal NRZ. Loads were added
      under four conditions: normal breathing, fixed flow rate, fixed breathing rate,
      and fixed flow and breathing rate. The pressure-flow technique was used to
      measure NRZ under all conditions. The study revealed that the sensation of
      breathing difficulty occurred at a median resistance of 5 cm H2O/L/sec and, as
      subjects were constrained to maintain fixed flow and breathing rates, the
      magnitude of RZ, at which the sensation of dyspnea was noted, decreased. The
      values observed in this study support previous findings suggesting that
      individuals switch to some oral breathing to maintain an adequate level of upper
      airway resistance at values between 3.5 and 4.5 cm H2O/L/sec. The findings also
      show that individuals attempt to minimize increases in airway resistance by
      modifying breathing behaviors.

PMID- 8734725
TI  - Midsagittal velar kinematics during production of VCV sequences.
AB  - We present data on velar speech movements examined by electromagnetic
      articulography (EMA), a tool for the study of velar kinematics. Based on
      investigations on 22 normal German subjects (15 male, 7 female), movement paths
      of the velum using a sensor positioned on the midsagittal anterior surface were
      recorded using a series of high and low vowel VCV utterances. Maximum velar
      elevation (mean = 13.5 +/- 0.6 mm [SD]) with the rest position as a reference was
      observed during the production /iti/. The average maximum articulatory velocity
      of velar movements during /iti/ production was 141.0 mm/sec. Maximum movement of
      the velum observed during production of /ana/ averaged 7.5 +/- 1.1 mm. The
      direction of velar movement ranged between 44.6 degrees and 50.4 degrees relative
      to the bite plane registered electromagnetically. The influence of loudness
      variation of sequence production is demonstrated and discussed with the
      literature.

PMID- 8734726
TI  - Three-dimensional comparison between the palatal forms in infants with complete
      unilateral cleft lip, alveolus, and palate (UCLP) with and without Hotz's plate.
AB  - A three-dimensional measuring system was developed to analyze changes in palatal
      forms of UCLP infants. This system quantified the change of the curved surface on
      a palate by automatically superimposing two wireframe models obtained from casts
      at different stages of growth. It also analyzed the curvature of the palatal
      surface. This system was used to study the palates of 20 infants with unilateral
      cleft lip and palate (UCLP), from the first to fourth months after birth (12 with
      Hotz's plate and 8 without, selected at random). Both major and lesser maxillary
      segments without Hotz's plate remained anterior and lateral although those with
      Hotz's plate moved mesially during the fourth month after birth. In addition, the
      degrees of curvature on the palatal surfaces with Hotz's plate were less than
      those without Hotz's plate.

PMID- 8734727
TI  - Bilaterally involved Tessier No. 4 cleft: case report.
AB  - Craniofacial clefts are rare among facial anomalies, with an incidence of 1.5 to
      5 per 100,000 births, and 1 per 100 cases of cleft lip and palate. The Tessier
      No. 4 oro-ocular cleft is one of the rarest, with 33 unilateral and bilateral
      clefts reported in the literature. Among the bilateral clefts only 3 of 9
      involved Tessier No. 4 cleft bilaterally. We report a case of bilateral Tessier
      No. 4 craniofacial cleft and our approach to surgical correction.

PMID- 8734728
TI  - Palatal mucoperiosteal expansion as an adjunct to palatal fistula repair: case
      report and review of the literature.
AB  - Case report of conventional palatal soft-tissue expansion in an attempt at cleft
      palate fistula closure with a standard tissue expander. This technique may be an
      alternative to a tongue flap to promote closure of persistent oronasal fistula.

PMID- 8734729
TI  - Presurgical anxiety treated with cognitive behavioral therapy in a 13-year-old
      female with cleft lip and palate: a psychological case report.
AB  - This case report describes presurgical anxiety in a 13-year-old female with
      complete cleft lip and palate, treatment of the anxiety with cognitive-behavioral
      therapy and progressive relaxation with biofeedback prior to a septorhinoplasty,
      and the treatment outcome.

PMID- 8734730
TI  - Early surgery for repairing cleft lip and palate.

PMID- 8734731
TI  - Congenital palatal ulcers in newborn infants with cleft lip and palate.

PMID- 8734732
TI  - Staging and prognosis of T3b bladder cancer.
AB  - Individuals with extravesical extension of bladder cancer (stage T3b) have a
      worse prognosis than those with muscle-invasive disease confined to the bladder.
      Accurate staging of T3b bladder cancer becomes increasingly important as more
      effective methods of treating high-stage bladder cancer are developed. Despite
      aggressive attempts over the last three decades to stage muscle invasive disease
      more accurately, bladder cancer is still staged incorrectly in 30% to 50% of
      patients. The basis for accurate clinical staging resides in a thorough
      endoscopic resection and a careful bimanual examination. Imaging studies
      (transurethral ultrasonography, computed tomography [CT], and magnetic resonance
      imaging [MRI] can increase the accuracy of staging but are most reliable when
      performed before transurethral resection.

PMID- 8734733
TI  - Characteristics of invasive bladder cancers: histological and molecular markers.
AB  - Changes in gene expression permit the emergence of clones of cancer cells with
      biological properties that enable invasion and metastasis. We present in this
      article an overview of the variety of genetic and antigenic markers that have
      been reported for invasive bladder cancer. Although the prognostic and diagnostic
      usefulness of many of these markers in invasive bladder cancer remains to be
      fully evaluated, this review will serve as a resource for the clinician on the
      current state of the field. Alterations in the biology and genetics of cells no
      doubt contribute to the processes of invasion and metastasis and are likely to
      provide important, useful information for future identification and management of
      the patient with invasive bladder cancer.

PMID- 8734734
TI  - Radical cystectomy for stage T3b bladder cancer.
AB  - Radical cystectomy with pelvic lymphadenectomy is the mainstay of treatment of
      muscle-invasive transitional cell carcinoma of the bladder. Outcome in patients
      with pathologically organ-confined disease is excellent, with local control rates
      exceeding 90% and 5-year survival approaching 80%. It is apparent, however, that
      radical cystectomy alone is inadequate therapy for patients with clinical or
      pathological extravesical extension. These patients are at high risk for relapse
      both locally and distantly. The development of more effective chemotherapy and
      optimal integration of systemic therapy with locally applied therapeutic
      modalities are needed. Recent data suggest that patients with clinical
      extravesical extension (T3b/T4) may benefit from combined local therapy with the
      addition of preoperative radiotherapy as well as multi-agent systemic
      chemotherapy. Furthermore, it appears that clinical staging modalities are
      reliable in the selection of patients for this multi-modal approach with only a
      small number of patients thereby subjected to unnecessary treatment.

PMID- 8734735
TI  - The role of chemotherapy in the management of the patient with T3b bladder
      cancer.
AB  - At present, it is clear that chemotherapy can contribute to improved outcome for
      some patients with locally advanced bladder cancer. For patients in clinical
      stage T3b, the incidence of pathological node involvement is no high that little
      is lost by giving up precise staging, and neoadjuvant therapy is probably the
      preferred approach. This is based on improved tolerance for chemotherapy,
      improved resectability rates, and the desirability of addressing metastatic
      disease at the earliest opportunity. Although more experience is needed, at
      present the surgical complication rate for cystectomy after chemotherapy does not
      appear to be significantly higher than immediate surgery. For patients thought to
      have T2/3a lesions according to clinical evaluation who are subsequently found to
      have stage pT3b at operation, the evidence for benefit from chemotherapy is not
      yet conclusive, and we consider use of adjuvant therapy in this setting to be
      investigational. It is hoped that refinement of clinical markers and continued
      improvement in combination regimens will allow more effective therapy to be
      targeted more selectively in the future.

PMID- 8734736
TI  - Radiotherapy for stage T3b transitional cell carcinoma of the bladder.
AB  - The role of radiotherapy for the treatment of clinical stage T3b transitional
      cell carcinoma of the bladder is controversial. The options range from definitive
      radiotherapy alone, to preoperative radiotherapy and cystectomy, to chemotherapy
      and radiation for bladder preservation. Our data show that long-term local
      control after definitive radiotherapy is only 27% and that death attributable to
      local-regional failure in this setting is 43%. Thus, definitive radiotherapy is
      only used in patients who are considered poor candidates for surgical and
      chemotherapy procedures. Preoperative radiotherapy (PREOP) has been studied in a
      number of randomized series, all of which failed to establish an improvement in
      patient outcome over those treated with radical cystectomy alone (CYST). However,
      these studies are subject to criticism, mostly because of poor patient accrual
      and low numbers of patients available for the analyses. A retrospective review of
      patients treated at MD Anderson Cancer Center indicates that local control is
      superior with PREOP as compared with CYST. An analysis of the impact of local
      control on distant metastasis rates in patients treated with CYST showed that
      local control was an independent correlate of distant metastasis and survival.
      Thus, preoperative radiotherapy may be beneficial to patients with late-stage
      muscle-invasive bladder cancer by securing local control and reducing distant
      metastasis rates as a result. The success of bladder preservation for stage T3b
      patients rests with the ability to select patients with radiosensitive tumors. To
      this end, the immunohistochemical staining status of tumor p53 and pRB was
      investigated in patients treated with PREOP. Abnormal pRB expression was very
      strongly related to radiation response, whereas altered p53 expression was
      associated with high distant metastasis-free and overall survival rates. These
      two molecular markers were complementary and show promise in facilitating the
      selection of late-stage patients for bladder preservation.

PMID- 8734737
TI  - What to do if the lymph nodes are positive.
AB  - Lymph node metastases are common in patients with advanced bladder cancer.
      Survival rates have apparently improved from about 15% to 30% as management
      evolved from lymphadenectomy plus cystectomy to multimodal therapy, but
      investigators have not conclusively shown the benefit of adjuvant irradiation
      and/or chemotherapy. If clinical staging indicates nodal metastases, we recommend
      primary multiagent chemotherapy with subsequent exploratory laparotomy,
      lymphadenectomy, and possibly cystectomy for complete responders. Patients
      without clinical evidence of metastases undergo complete bilateral pelvic
      lymphadenectomy plus cystectomy if nodes are normal, or if grossly abnormal but
      resectable. Patients with nodal metastases may be candidates for adjuvant
      chemotherapy.

PMID- 8734738
TI  - Bladder preservation and continent urinary diversion in T3b transitional cell
      carcinoma of the bladder.
AB  - The patient with T3b transitional cell carcinoma (TCC) of the bladder has
      traditionally been treated with radical cystectomy and urinary diversion, but
      initial success with systemic chemotherapy and renewed interest in quality-of
      life issues has increased interest in bladder preservation treatments.
      Unfortunately, despite multiple trials using limited surgical procedures and
      neoadjuvant or adjuvant chemotherapy, no combined modality has consistently
      improved survival over the achieved with radical cystectomy alone in patients
      with T3b disease. Additionally, continent stomal diversions and orthotopic
      neobladders allow almost normal continence and voiding in both male and female
      patients, which calls into question the need for bladder preservation. Although
      no single treatment modality or urinary diversion is right for all patients, a
      radical cystectomy with continent diversion provides the best chance for survival
      and allows the best postoperative quality of life. If bladder preservation
      treatments are used, inclusion in a clinical trial is recommended.

PMID- 8734739
TI  - The management of locally recurrent invasive bladder cancer following radical
      cystectomy.
AB  - Local recurrence of invasive bladder cancer after radical cystectomy has an
      aggressive natural history with a poor prognosis. Most patients with this
      difficult clinical problem have either objective or subclinical metastatic
      disease. Accordingly, patients should be treated with a multimodality approach
      that includes systemic treatment (chemotherapy) as well as aggressive local
      treatments, such as surgery and radiation therapy. Although the prognosis is
      generally poor, long-term disease-free survival is achievable in a few patients
      with a multimodality treatment approach

PMID- 8734740
TI  - Indications for permanent cardiac pacing in first-degree AV block: class I, II,
      or III?

PMID- 8734741
TI  - Effects of high energy shocks on pacing impedance during transvenous ICD
      implantation.
AB  - The purpose of the current study was to characterize the effects of transvenous
      ICD shocks on myocardial impedance. Rather than recording impedance during
      shocks, it was measured during continuous pacing in order to minimize confounding
      effects such as electrode polarization. Pacing impedance (reflecting the combined
      impedances of the electrode-tissue interface, myocardium, and blood pool) was
      measured every 5 seconds before and after 58 single shocks in 22 patients
      undergoing ICD implantation with a Transvene (n = 14) or Endotak (n = 8) lead.
      There was a progressive and long-lasting decrease in impedance after shocks. The
      magnitude of this change was similar for 0.6-J test shocks and shocks > or = 5 J
      (28 +/- 32 omega vs 23 +/- 16 omega; P = 0.8). However, the drop in impedance was
      more abrupt after high energy shocks. Because impedance continued to decline
      throughout the 5-minute interval between shocks, successive shocks had a
      cumulative effect, with a decrease of 46 +/- 42 omega after four discharges. In
      conclusion, a progressive decline in pacing impedance is a characteristic
      response to transvenous ICD discharges.

PMID- 8734742
TI  - Influence of age, lead axis, frequency of arrhythmic episodes, and atrial
      dimensions on P wave triggered SAECG in patients with lone paroxysmal atrial
      fibrillation.
AB  - Signal-averaged P wave of 42 patients with lone paroxysmal atrial fibrillation
      (PAF) and 29 normal subjects (N) were recorded, using three orthogonal leads and
      analyzed in the time and frequency (entire P wave or a 100-ms segment ranging
      from 75 ms before to 25 ms after the end of P wave) domains. PAFs were divided
      into a group of 12 having > or = 2 attacks a month (HF) and a group of 30 having
      < or = 2 attacks a year (LF). Statistically significant differences were absent
      with regard to ages of PAF and N; ages of HF, LF, and N at the time of signal
      averaged ECG; ages of HF and LF at the time of the first arrhythmic episode; and
      elapsed times from the first episode. Length of P wave and some frequency-domain
      parameters were found to be significantly correlated with age. PAF showed a
      significantly longer duration of P wave in the frontal plane using the time
      domain analysis. Frequency analysis was found to be useful in evaluating the
      influence of attack frequency. HF showed significantly higher values of some
      frequency-domain parameters than LF and N, while the three groups did not differ
      for time-domain analysis. P wave duration and frequency content of the three
      orthogonal leads proved to be significantly different in PAF and N. Right and
      left atrial echocardiographic dimensions proved to be higher (even if within
      normal limits) in HF than in LF and N. Results suggest that frequency analysis
      should be performed on the entire P wave.

PMID- 8734743
TI  - A critical appraisal of quantitative spectro-temporal analysis of the signal
      averaged ECG: predicting arrhythmic events after myocardial infarction.
AB  - The objective of this study was to determine if spectro-temporal analysis of the
      signal-averaged ECG (SAECG) predicts spontaneous sustained ventricular
      tachyarrhythmias and sudden death in patients prospectively followed after
      myocardial infarction (MI). A SAECG was recorded in 177 patients 9 +/- 5 days
      after MI. Spectro-temporal analysis of the SAECG involved incrementing a Hanning
      window every 3 ms beginning 20 mg before the end of the QRS complex and extending
      into the ST segment. Quantitative analysis was performed using a cross
      correlation function to create a normality factor. A normality factor < 0.3 was
      deemed abnormal. The SAECG was abnormal in 41% of patients using time-domain
      analysis and 44% of patients using spectro-temporal analysis. There was no
      correlation between an abnormal SAECG in the time domain and the frequency
      domain. Patients with inferior wall MI were more likely to have an abnormal
      spectro-temporal map (odds ratio 2.26, P < 0.05). Time-domain analysis of the
      SAECG (relative risk (RR) 2.6) was a statistically significant univariate
      predictor of arrhythmic events. Spectro-temporal analysis of the SAECG was only
      weakly (RR 1.8) and not significantly (P = 0.15) associated with the spontaneous
      occurrence of these arrhythmias. When both time-domain analysis and spectro
      temporal analysis of the SAECG were abnormal, the relative risk for an arrhythmic
      event was increased by 3.3-fold. Quantitative spectro-temporal analysis of high
      frequency signals within the SAECG cannot by itself predict the occurrence of
      spontaneous ventricular arrhythmias in patients after MI.

PMID- 8734744
TI  - Lead extraction in young patients with and without congenital heart disease using
      the subclavian approach.
AB  - Pacemaker lead removal using interlocking stylets and dilator sheaths has greatly
      reduced the need for major surgical intervention when lead extraction is
      required. Previous reports have shown the utility of this method in older
      patients, most of whom have anatomically normal hearts. The purpose of this study
      is to report the results of this technique in young patients with and without
      congenital heart disease. There were 13 patients (M:F = 7:6) aged 9-26 years
      (median 13). Congenital heart disease was present in 8 of 13 patients. A total of
      17 leads required removal; they had been implanted for 54 +/- 24 months (range 19
      94). Leads were removed from the left subclavian vein (13) or right subclavian
      vein (4) only. Seventeen of 18 leads were completely removed and one partially
      retained in the left subclavian vein. New leads were implanted from the same vein
      in 11 of 13 patients. Interlocking stylets and metal or flexible dilator sheaths
      were used in all cases except two. There was one surgical complication: a late
      wound dehiscence, which was easily managed. No patient required a transfusion,
      and there was no structural damage noted in any patient on the postoperative
      echocardiogram. We conclude that lead removal using interlocking stylets and
      dilator sheaths from the subclavian approach is an effective technique that can
      be used in young patients, including those with congenital heart disease.

PMID- 8734745
TI  - Prospective evaluation of infrahisal second-degree AV block induced by atrial
      pacing in the presence of chronic bundle branch block and syncope.
AB  - The value of nonfunctional infrahisal second-degree atrioventricular (AV) block
      induced by incremental atrial pacing was prospectively examined in 192 patients
      with chronic bundle branch block (BBB) and syncope. We compared 174 (91%)
      patients with normal response to atrial pacing (Group I) to 18 (9%) patients with
      atrial pacing induced nonfunctional infrashisal second-degree AV block (Group
      II). Patients in group I had higher incidence of organic heart disease,
      ventricular tachycardia induction, and retrograde ventriculoatrial conduction (P
      < 0.001, P < 0.05, P < 0.01, respectively), while patients in group II had higher
      incidence of primary conduction disease and prolonged H-V intervals (P < 0.001, P
      < 0.01, and P < 0.001). During mean follow-up period of 65 +/- 34 months for
      group I, and 68 +/- 35 months for group II, a development of spontaneous second-
      or third-degree AV block was higher in group II (14/18 [78%]), than in group I
      (15/174 [9%]) (P < 0.001). The site of AV block was infrahisal in all patients in
      group II, and in 10 of 15 patients in group I. Because of the prophylactic pacing
      in all patients in group II, the incidence of sudden death was similar among the
      two groups, but patients in group I had higher incidence of cardiac death (P <
      0.05). CONCLUSION: In patients with chronic BBB and syncope, a nonfunctional
      infrashisal AV block induced by incremental atrial pacing identified patients
      with particularly high risk of development of spontaneous infrahisal AV block.
      Therefore, permanent cardiac pacing is absolutely indicated in these patients.

PMID- 8734746
TI  - Normal values for the childhood signal-averaged ECG.
AB  - To obtain normative data for the childhood signal-averaged ECG (SAECG), we
      obtained SAECGs in 155 volunteers, aged 5-15 years, using Frank leads and a
      Fourier transform filter. Unfiltered QRS duration (QRSDU) and filtered QRS
      duration (QRSDF) were significantly longer in males, and the root mean square of
      the terminal 40 ms (RMS40) was significantly higher in females. There were no
      gender differences in the duration of high frequency low amplitude signals < 40
      microV (DHFLA). All SAECG variables were significantly related to body surface
      area (BSA). Regression models were established for SAECG variables. For males,
      the predicted mean + 1.96 standard deviations (SD) for QRSDF (97.5th centile)
      ranged from 114 ms at BSA 0.70 m2 to 123 ms at 1.90 m2. For females, the
      predicted mean + 1.96 SD for QRSDF ranged from 110 ms at BSA 0.70 m2 to 119 ms at
      1.90 m2. For males and females, the predicted mean + 1.96 SD for DHFLA ranged
      from 34 ms at 0.70 m2 to 38 ms at 1.90 m2. For males, the predicted mean - 1.96
      SD (2.5th centile) for RMS40 (based on natural logarithm model) ranged from 30
      microV at 0.70 m2 to 15 microV at 1.90 m2. For females, the predicted mean -1.96
      SD for RMS40 ranged from 42 microV at 0.70 m2 to 20 microV at 1.90 m2. In
      children 5-15 years of age, both gender and BSA need to be taken into account
      when interpreting the SAECG.

PMID- 8734747
TI  - Electrophysiological, rate dependent, and autonomic effects of the class III
      antiarrhythmic almokalant after myocardial infarction in the pig.
AB  - Ventricular arrhythmias remain a major problem, in particular in patients with
      left ventricular dysfunction or heart failure. In this group of patients, Class I
      drugs were shown to be ineffective, and they even increased mortality during
      chronic treatment. New antiarrhythmic agents should preferably not only have pure
      antiarrhythmic effects, but should also be free from adverse autonomic
      properties. In the present study, the electrophysiological, rate dependent and
      autonomic effects of intravenously administered almokalant, a new Class III
      antiarrhythmic drug, were investigated in nine pigs surviving a myocardial
      infarction. The ventricular effective refractory period (VERP) increased after
      almokalant (loading dose: 0.05 mumol.kg-1.min-1, continuous infusion: 0.0025
      mumol.kg-1.min-1) from 292 +/- 25 to 308 +/- 13 ms (pacing cycle length [PCL] 500
      ms + 1 extrasystole [ES]), from 249 +/- 19 to 261 +/- 16 ms (PCL 400 ms +1ES),
      and from 209 +/- 18 to 219 +/- 18 ms (PCL 300 ms +1ES). The VERPs increased most
      after three ES at PCL 400 ms: from 167 +/- 27 to 186 +/- 29 ms (P < 0.05) and at
      PCL 300 ms: from 150 +/- 29 to 174 +/- 27 ms (P < 0.05). The ventricular
      monophasic action potential durations (MAPD) were similarly prolonged and the
      ratio VERP/MAPD did not change. Prolongation of MAPD after almokalant remained
      present at short pacing cycle lengths. Before almokalant infusion, sustained
      monomorphic ventricular tachycardia (VT) was inducible in two pigs, and
      nonsustained VT in a third animal. After almokalant, only one pig remained
      inducible. Two weeks after myocardial infarction, heart rate variability and
      baroreflex sensitivity were reduced. Furthermore, subsequent electrophysiological
      testing transiently reduced these parameters of autonomic activity. During
      almokalant however, no changes in autonomic functions were observed after
      programmed stimulation. Heart rate variability decreased after myocardial
      infarction from 6.3 +/- 2.5 ms to 5.4 +/- 4.2 ms (P = NS). After programmed
      stimulation, it further decreased to 2.8 +/- 2.0 ms (P = 0.028). Almokalant
      infusion prevented autonomic deterioration: 3.3 +/- 2.2 ms before stimulation and
      3.3 +/- 1.3 after stimulation (P = NS). In postinfarct pigs, almokalant prolongs
      VERP and MAPD at shorter pacing cycle lengths. The results indicate absence of
      reverse rate dependence and of adverse autonomic changes.

PMID- 8734748
TI  - Performance of implantable defibrillator pacing/sensing lead adapters.
AB  - The wide variety of implantable defibrillators (ICDs) available from different
      manufactures and the lack of universal industry standards has resulted in the
      frequent need for lead adapters at time of ICD implant or change. We analyzed the
      performance of 81 consecutive ICD sensing/pacing lead adapters used between 1988
      and 1993. A total of 66 adapters was used for new epicardial systems, and 15
      adapters served as lead connectors during ICD generator replacement.
      Pacing/sensing lead adapters used were: model LA-201 (n = 28; 34.5%); model 030
      308 (n = 26; 32%); model 5866-24 (n = 15; 18.5%); and miscellaneous (n = 12;
      15%). After a mean follow-up of 21 +/- 16 months, nine pacing/sensing lead
      adapters had documented or strongly suspected failure. Most often pacing/sensing
      lead adapters presented clinically as frequent aborted shocks. Actuarial
      probability of freedom from failure for model LA-201 was 83% at 1 year, and 72%
      at 2 and 3 years; this was poorer than for the other sensing leads combined (P =
      0.01; hazard ratio = 4.92; 95% confidence intervals = 1.2-20; log-rank test). In
      conclusion, pacing/sensing lead adapters are a potential source of ICD system
      complications. Performance is dissimilar among different models; specifically,
      model LA-201 may not be safe in the long-term, and patients with this lead
      adapter need to be closely monitored.

PMID- 8734749
TI  - Acute and chronic changes in atrial natriuretic factor induced by ventricular
      pacing: a self controlled clinical trial.
AB  - A self controlled clinical trial was carried out to study the acute and chronic
      effects of ventricular pacing (VVI) on the atrial natriuretic factor (ANF).
      Eleven people were selected from a pool of 20 DDD paced patients. Pacemakers were
      programmed to the VVI mode for 1 month and their effectiveness tested by ECG at
      rest and after an effort test. AnF was measured by radioimmunoassay at baseline,
      after 15 minutes, and again 1 month after programming. The reliability of the
      radioimmunoassay was confirmed using the coefficients of variation between
      (12.5%) and within assay (9.7%). Data analysis was done using Wilcoxon's test.
      Our results showed that the onset of VVI pacing led to a sudden sharp rise in ANF
      in all patients (P < 0.0001). During VVI pacing, three patients were dropped from
      the study (2 were withdrawn because of symptoms and 1 voluntarily withdrew).
      After 1 month of VVI pacing, a significant increase of ANF above the baseline was
      observed (P < 0.05). The results showed that ventricular pacing led to an
      immediate rise in ANF and, that with long-term VVI pacing, there was an increase
      in ANF levels as well. The role of these findings in the pathophysiology of the
      pacemaker syndrome calls for further research.

PMID- 8734750
TI  - Overnight heart rate and cardiac function in patients with dual chamber
      pacemakers.
AB  - Animal data indicate that chronic, overnight pacing at normal evening heart rates
      impairs cardiac function. We examined the relationship of pacing rate and cardiac
      function in nine patients with dual-chamber pacemakers. We investigated two, 3
      week pacing regimens (80 and 50 ppm: DDD mode) in a cross-over design. Doppler
      echocardiograms were performed at 1700 hours (PM) and 0600 hours (AM) at the end
      of each regimen. Ventricular function and preload decreased overnight (PM vs AM)
      with both pacing regimens. Compared to the morning values, the ratio of
      preejection to ejection time (PEP/ET) rose (0.43 vs 0.46), while the mean
      velocity of circumferential fiber shortening (Vcf) fell (1.16 cm/s vs 1.11 cm/s).
      Stroke volume (SV) (61 mL vs 53 mL) and ejection fraction (EF) also fell (0.56 vs
      0.53) in the morning. End-diastolic volume (EDV) (94 mL vs 88 mL) decreased in
      the morning, as did the ratio of passive to active filling (E/A) (1.06 vs 0.96).
      Isovolumic relaxation time (91 ms vs 101 ms) increased overnight at both pacing
      rates. Systolic function decreased at 80 ppm relative to 50 ppm at both times of
      day. SV fell (54 mL vs 61 mL), while both EDV (92 mL vs 90 mL) end-systolic
      volume (ESV) increased (43 mL vs 40 mL). Contractility measured by Vcf (1.09 cm/s
      vs 1.18 cm/s) and PEP/ET (0.49 vs 0.41) was reduced at 80 ppm. The heart needs to
      rest at night by slowing its rate of contraction. Pacing at 80 ppm impairs
      systolic and diastolic ventricular function compared to 50 ppm. Longer term
      consequences of ostensibly physiological pacing rates merit inquiry, particularly
      in those with preexisting cardiac dysfunction.

PMID- 8734751
TI  - Long-term thresholds of nonsteroidal permanent pacing leads: a 5-year study.
AB  - The present commercial market supports many nonsteroidal endocardial pacing leads
      of differing construction. In order to compare the performance of these
      configurations, we studied the long-term pacing properties of three
      representative lead types by randomized clinical trial in 99 patients undergoing
      a first elective VVI implant. Thirty-one patients received sintered platinum
      leads, 36 activated pyrolytic carbon leads, and 32 vitreous carbon leads. All
      received generators capable of noninvasive threshold testing. Acute sensing
      parameters were R wave amplitude and ST segment elevation measured from the
      endocardial electrogram. Noninvasive voltage thresholds were measured at
      implantation, 2 days, 1, 3, and 6 months, and yearly thereafter for 5 years.
      There were no significant differences between leads in pacing or sensing
      capabilities at implantation. All three demonstrated similar increases in
      thresholds, peaking at 1 month, then falling to a plateau by 6 months and did not
      vary significantly thereafter. There were no significant differences in
      thresholds between leads during 5 years of follow-up. The lowest mean threshold
      at 5 years was 0.93 V at 0.5 ms. This study suggests that: (1) although these
      lead types all perform well, none offers any particular clinical advantage over
      another; (2) the degree of early threshold peaking precludes immediate
      postimplant output reduction, but later thresholds are sufficiently low to enable
      reductions in pacing output; (3) safe low energy pacing requires greater
      attention to the lead-generator combinations; (4) data obtained at subsequent
      annual follow-up provided no additional useful clinical information to that
      obtained at 1 year; and (5) in the absence of other differences, cost can be the
      deciding factor in lead selection.

PMID- 8734752
TI  - The use of methylphenidate in the treatment of refractory neurocardiogenic
      syncope.
AB  - Recurrent neurocardiogenically mediated episodes of hypotension and bradycardia
      are a common cause of recurrent syncope that can be identified by head upright
      tilt table testing. While the use of beta-blockers, theophylline,
      fludrocortisone, disopyramide, and serotonin re-uptake inhibitors can be helpful
      in preventing further episodes, some patients are unresponsive to or poorly
      tolerant of these agents. We investigated the use of the central nervous system
      stimulant and peripheral vasoconstrictor methylphenidate in preventing both tilt
      induced and spontaneous neurocardiogenic syncope. Seven patients (all women, mean
      age 31 +/- 15 years) with recurrent syncope and positive head upright tilt
      induced hypotension/bradycardia (refractory to normal therapy) were placed on
      methylphenidate 10 mg orally three times per day. Six of the seven patients
      became both tilt negative and clinically asymptomatic over a 7-month follow-up
      period. We conclude that methylphenidate may be an effective therapy in patients
      with recurrent neurocardiogenic syncope refractory to other forms of therapy.

PMID- 8734753
TI  - Atrial flutter mapping and ablation. I. Studying atrial flutter mechanisms by
      mapping and entrainment.
AB  - Endocardial mapping has led to a detailed knowledge of reentry mechanisms in
      atrial flutter. Multipolar and deflecting tip catheters allow recording local
      electrograms from multiple areas of the right atrium, and from the coronary
      sinus. In common flutter, with the typical "sawtooth" pattern, there is circular
      activation of the right atrium in a "counterclockwise" direction, descending in
      the anterior and lateral walls, and ascending in the septum and posterior wall.
      Superior and inferior vena cava, linked by a "line" of functional block in the
      posterolateral wall, make the central obstacle for circular activation. The
      cranial and caudal turning points are the atrial "roof," and the isthmus between
      the inferior vena cava and the tricuspid valve. Complex conduction patterns,
      probably including slow conduction are detectable in the low septal area, around
      the coronary sinus. Atypical flutter, without the sharp negative deflections of
      common flutter, sometimes shows circular activation in the right atrium, rotating
      in the opposite direction of common flutter (clockwise). Other atypical flutters
      show no circular right atrial activation, and only partial data from coronary
      sinus activation, combined with the response to atrial stimulation (entrainment)
      allow the diagnosis of left atrial reentry, without a precise delimitation of the
      circuits. In patients having undergone cardiac surgery, atypical flutter may be
      based on reentry around surgical scars. To our knowledge, the mechanism of type
      II flutter has not been disclosed in humans.

PMID- 8734754
TI  - Palmtop computers and the physician.

PMID- 8734755
TI  - Manpower needs in pacing and electrophysiology: taking a closer look.

PMID- 8734756
TI  - An irregularly irregular rhythm.

PMID- 8734757
TI  - Problems in managing patients with long QT syndrome and implantable cardioverter
      defibrillators: a report of two cases.
AB  - Implantable cardioverter-defibrillators (ICDs) have been a successful adjunct to
      the management of arrhythmias in patients with Long QT syndrome (LQTS). In two
      patients, interactions between LQTS and the ICD were diagnosed and corrected.
      Oversensing of T waves was confirmed in the first, while in the second, the
      arrhythmia disappeared when T wave abnormalities improved after cessation of H2
      blocker therapy. In patients with LQTS and an ICD, T wave oversensing should be
      considered. Interventions that may have an adverse effect on repolarization
      should be avoided.

PMID- 8734758
TI  - Undersensing of the tiny QRS complexes that emerged after the isolation of the
      right ventricle in a patient with ventricular tachycardia.
AB  - This article describes a patient who underwent right ventricular disconnection
      for medically refractory ventricular tachycardia associated with arrhythmogenic
      right ventricular dysplasia. After the operation there was no ventricular
      tachycardia recurrence. Two years after the operation, he received a permanent
      VVI pacemaker for the symptomatic second-degree AV block. Sensing function of the
      pacemaker was normal for the normal QRS complexes, but the tiny QRS complexes
      that appeared after the arrhythmia surgery were not sensed by the pacemaker and
      therefore caused no problem.

PMID- 8734759
TI  - Internal cardioversion in two patients with atrial fibrillation refractory to
      external cardioversion.
AB  - A 26-year-old man underwent an electrophysiological study for evaluation of a
      history of congenital heart disease, presyncope, and wide complex tachycardia.
      During the study the patient developed sustained atrial fibrillation with a rapid
      ventricular response. A 17-year-old man with a history of sick sinus syndrome
      developed sustained atrial fibrillation. Both patients failed four attempts at
      external cardioversion with a maximum delivered energy of 360 J. Low energy
      cardioversion was successful in both patients using biphasic waveforms and
      internal transvenous defibrillation electrodes. Internal cardioversion using a
      transvenous electrode system can be successful in patients with atrial
      fibrillation refractory to external cardioversion.

PMID- 8734760
TI  - New approach to subclavian venipuncture.

PMID- 8734761
TI  - An unusual complication in pacemaker therapy.

PMID- 8734762
TI  - Diagnosis of wide complex tachycardia.

PMID- 8734763
TI  - Effect of a NO donor (glyceryl trinitrate) on nociceptive thresholds in man.

PMID- 8734764
TI  - Families linked and unlinked to chromosome 19 with familial hemiplegic migraine.

PMID- 8734765
TI  - Familial hemiplegic migraine: a clinical comparison of families linked and
      unlinked to chromosome 19.DMG RG.
AB  - We compared the clinical characteristics of 46 patients from three unrelated
      families with familial hemiplegic migraine (FHM) linked to chromosome 19, with
      those of 20 patients from two families with FHM not linked to chromosome 19. We
      found no significant differences for age at onset, frequency and duration of
      attacks, duration of the paresis, and occurrence of basilar migraine symptoms. In
      the linked families, significantly more patients reported unconsciousness during
      attacks (39% vs 15%; p < 0.05) and provocation of attacks by mild head trauma
      (70% vs 40%; p < 0.05). In one linked family patients also displayed chronic
      progressive cerebellar ataxia, whereas in one unlinked family benign infantile
      convulsions occurred in addition to FHM. Interestingly, so far an association
      with cerebellar ataxia was only described in chromosome 19-linked families. FHM
      linked to chromosome 19 and FHM unlinked to chromosome 19 do not differ with
      respect to clinical features.

PMID- 8734766
TI  - The family history of migraine. Direct versus indirect information.
AB  - Migraine assessed by proband report was evaluated in a family study of migraine.
      A clinical interview of spouses and first-degree relatives by a physician was
      used as an index of validity. The operational diagnostic criteria of the
      International Headache Society were used. Of the 378 probands from the general
      population, 126 had migraine without aura, 127 had migraine with aura, 17 had
      both migraine without aura and migraine with aura and 108 had never had migraine.
      Spouses (n = 229) and first-degree relatives (n = 1109) were included in the
      analyses. Sensitivity, specificity, predictive values and chance-corrected
      agreement rate for the diagnosis of migraine were 49%, 93%, 81% (PVpos), 77%
      (PVneg) and 0.47, respectively. The corresponding values for migraine without
      aura were 58%, 87%, 63% (PVpos), 84% (PVneg) and 0.46 respectively, while the
      values for migraine with aura were 52%, 88%, 61% (PVpos), 83% (PVneg) and 0.42,
      respectively. Migraine assessed by proband report is not satisfactory for
      diagnosing migraine in relatives, since the number of affected relatives is
      highly underestimated. Our results emphasize the necessity of a clinical
      interview of the relatives in family studies of migraine.

PMID- 8734767
TI  - Regional cerebral blood flow (rCBF) in migraine during the interictal period:
      different rCBF patterns in patients with and without aura.
AB  - The aim of this study was to evaluate the rCBF (133Xe clearance method) in
      migrainous patients free from attack. Fifty patients suffering from migraine
      without aura (group M) and 20 suffering from migraine with aura (group MA) (age
      range 20-50 years) were submitted to 32 channel rCBF mapping during the
      interictal period. The rCBF data of patients were compared with those obtained
      from 60 healthy control subjects (group C) and 21 patients suffering from tension
      type headache (group TH). The mean (average of all channels) rCBF values were:
      group M = 70.5 +/- 13.7 ml/100g/min; group MA = 56.6 +/- 11.4 ml/100g/min; group
      C = 62.3 +/- 8.3 ml/100g/min; group TH = 62.1 +/- 8.4 ml/100g/min (F = 11.93; p <
      0.001). As expected, patients belonging to group TH had a normal rCBF. The mean
      rCBF of group M was significantly higher than that of groups C and TH, while in
      group MA it was significantly lower than in groups C and TH. Group M showed a
      diffuse hyperemia, while group MA showed rCBF values significantly lower than
      normal in posterior regions, according to aura. Our results suggest that: (a) the
      rCBF pattern in migrainous patients is different from that in both controls and
      TH patients, even during the interictal period; (b) patients suffering from
      migraine with and without aura are two distinct subpopulations with opposite rCBF
      deviations.

PMID- 8734768
TI  - Effect of a nitric oxide donor (glyceryl trinitrate) on nociceptive thresholds in
      man.
AB  - Several animal studies suggest that nitric oxide (NO) plays a role in central and
      peripheral modulation of nociception. Glyceryl trinitrate (GTN) exerts its
      physiological actions via donation of NO. The purpose of the present study was to
      examine the effect of this NO donor on nociceptive thresholds in man. On two
      different study days separated by at least a week 12 healthy subjects received a
      staircase infusion of GTN (0.015, 0.25, 1.0, 2.0 micrograms/kg/min, 20 min each
      dose) or placebo in a randomized double-blind crossover design. Before the
      infusion and after 15 min of infusion on each dose, pressure pain detection and
      tolerance thresholds were determined by pressure algometry (Somomedic AB, Sweden)
      in three different anatomic regions (finger, a temporal region with interposed
      myofascial tissue and a temporal region without interposed myofascial tissue).
      Relative to placebo, the three higher GTN doses induced a decrease in both
      detection and tolerance thresholds in the temporal region with interposed
      myofascial tissue (p = 0.003 detection and p = 0.002 tolerance thresholds,
      Friedman). No such changes were observed in the other two stimulated regions.
      These results could reflect central facilitation of nociception by NO. However,
      we regard convergence of nociceptive input from pericranial myofascial tissue and
      from cephalic blood vessels dilated by NO as a more likely explanation of our
      findings.

PMID- 8734769
TI  - Initiating mechanisms of experimentally induced tension-type headache.
AB  - To elucidate possible myofascial mechanisms of tension-type headache, the effect
      of 30 min of sustained tooth clenching (10% of maximal EMG-signal) was studied in
      58 patients with tension-type headache and in 30 age- and sex-matched controls.
      Pericranial tenderness, mechanical and thermal pain detection and tolerance
      thresholds and EMG levels were recorded before and after the clenching procedure.
      Within 24 h, 69% of patients and 17% of controls developed a tension-type
      headache. Shortly after clenching, tenderness was increased in the group who
      subsequently developed headache, whereas tenderness was stable in the group of
      patients who remained headache free. Mechanical pain thresholds evaluated by
      pressure algometry remained unchanged in the group which developed headache,
      whereas thresholds increased in the group which did not develop headache. Thermal
      pain detection and tolerance thresholds remained unchanged in both groups. These
      findings indicate that, although there may be several different mechanisms of
      tension-type headache, one of them is sustained muscle contraction. A peripheral
      mechanism of tension-type headache is therefore possible, whereas a secondary
      segmental central sensitization seems to be involved in subjects with frequent
      tension-type headache. Finally, the increase in pressure pain thresholds in
      patients who did not develop headache suggested that clenching activated their
      antinociceptive system, whereas those developing headache were unable to do so.

PMID- 8734770
TI  - A quality of life instrument for adolescents with chronic headache.
AB  - We developed a generic Quality of Life (QL) measurement scale for adolescents
      between 12 and 18 years of age, primarily for use on youngsters with chronic
      headaches or migraine. The Quality of Life Headache in Youth (QLH-Y) is a 71 item
      (69 multiple choice items and two visual analogue scales) QL measurement scale.
      It assesses an individual's QL in six QL subdomains. Study 1 (n = 223) was aimed
      at item selection and scale construction. Thirteen subscales were developed to
      cover the four QL subdomains Psychological Functioning, Functional Status,
      Physical Status and Social Functioning. The QL subdomains Satisfaction with Life
      in General and Satisfaction with Health were covered by two visual analogue
      scales. Internal consistency of nearly all the subscales was satisfactory. Study
      2 (n = 159) was conducted to evaluate the validity and stability of the QLH-Y.
      Indications for parent-youth agreement, construct validity and sensitivity for
      headache and migraine were obtained. Stability coefficients were between 0.47 and
      0.72 for the 1-week interval and between 0.31 and 0.60 for the 6-month interval.
      Nearly all of the QLH-Y subscales appeared to be more sensitive to differences
      between subjects with headaches and headache-free subjects, while the QL
      subdomain Functional Status was most sensitive for subjects who had suffered from
      a recent headache.

PMID- 8734772
TI  - Should we investigate migraine of late onset?

PMID- 8734771
TI  - Amitriptyline and dexamethasone combined treatment in drug-induced headache.
AB  - Frequent or regular intake of antimigraine drugs, including analgesics,
      constitutes a common cause of chronic daily headache. Discontinuation of
      symptomatic medication can produce an increase in head pain accompanied by
      withdrawal symptoms. We report the favourable outcome of treating a group of
      outpatients with the combination of amitriptyline, dexamethasone and sumatriptan.
      Dexamethasone (4 mg/day) was given intramuscularly for 2 weeks, amitriptyline
      orally at night (50 mg/day) for at least 6 months, and sumatriptan subcutaneously
      to treat acute headache attacks. Eighteen out of 20 patients abstained from drug
      abuse. Eleven of these 18 patients showed a marked reduction in headache
      frequency (at least 75% in relation to the basal value), and were considered
      "very good responders". The other seven patients experienced at least 50%
      reduction in headache frequency compared to baseline. This preliminary report
      suggests that drug-induced headache can be treated effectively in outpatients
      using dexamethasone, amitriptyline and sumatriptan in combination with
      significant benefit in everyday life conditions.

PMID- 8734774
TI  - Cervicogenic headache.

PMID- 8734773
TI  - Cluster headache syndrome associated with middle cerebral artery arteriovenous
      malformation.
AB  - Cluster headache (CH) is an idiopathic cephalalgic syndrome, although several
      pathological processes have been described in association with this syndrome. We
      report two cases of cluster headache in hospitalized patients with middle
      cerebral artery dependent arteriovenous malformation (AVM). After surgical
      removal of the AVM the headache completely resolved, suggesting that
      complementary studies and treatment of the underlying aetiology may be indicated
      for secondary forms of cluster headache.

PMID- 8734775
TI  - Three-dimensional reconstruction of the cochlea from two-dimensional images of
      optical sections.
AB  - This paper describes a methodology for three-dimensional (3D) computer-aided
      reconstruction of the guinea pig cochlea using orthogonal-plane fluorescence
      optical sectioning. Specimens are sectioned optically, allowing them to remain
      intact during observation. Equations to correct the data for specimen translation
      and rotation are developed and 3D reconstructions of the scala tympani, round
      window membrane, and cochlear aqueduct are presented. The error associated with
      the reconstruction is estimated to be < 19 microns.

PMID- 8734776
TI  - Diagnostic performance of CT, MPR and 3DCT imaging in maxillofacial trauma.
AB  - CT imaging of complex maxillofacial fractures is common practice now, but the
      relative diagnostic value of spiral computed tomography (CT), multiplanar
      reformations (MPR), and three-dimensional (3D) reconstructions in evaluating
      maxillofacial fractures is not established with independent validation of correct
      diagnosis. We studied these modalities and measured their diagnostic value in a
      carefully controlled observer based rated response experiment. Multiple fractures
      were created by blunt experimental trauma in nine adult cadaver heads (five
      males, four females). Spiral CT scans were performed on all specimens before
      (control) and after trauma. Axial slices (CT), sagittal and coronal multiplanar
      reconstructions (MPR), and 3D volumetric reconstructions views were generated.
      Truth was determined by defleshing the specimens and direct inspection of the
      traumatized skull. Three expert readers separately interpreted CT, MPR and 3D
      film hard copy images presented in random order blinded to patient identification
      or experimental conditions. We measured the time to diagnose each case as
      recorded by a monitor who was present while evaluations were performed. Twenty
      eight facial regions were evaluated using rated response and free response
      illustrative formats. Each region was considered separately. Sensitivity and
      specificity were calculated to measure observer performance. We found that 3D and
      CT had a similar performance in fracture detection and both were markedly better
      than MPR. For free response illustrative data, CT correctly identified 10% more
      orbital fractures than 3D, and approximately 10% fewer zygomatic fractures.
      Fracture localization was best with 3D. Reader confidence was highest with CT,
      but assessment time was faster with 3D. We conclude that CT and 3D are comparable
      in detecting midfacial fractures and both are superior to MPR. 3D reconstructions
      are superior for localization of complex fractures involving multiple planes.

PMID- 8734777
TI  - Cerebral cartography--a method for visualizing cortical structures.
AB  - We present a method for visualizing the human cortex on one planar map. The data
      are taken from a 3D MRI study. Ray tracing with non-parallel rays is used to
      project the cortical relief onto a non-planar projection surface, which is in
      turn mapped onto the plane by cartographical projection. Two modifications of the
      method are proposed: the spherical mapping uses a sphere as the projection
      surface; the model-based mapping uses an analytically defined model of the scalp
      to generate the normal vectors. The cerebral cartography can be used for example
      for producing anatomical reference maps on which EEG measurement data can be
      superimposed.

PMID- 8734778
TI  - Rubinstein-Taybi syndrome: cranial MR imaging findings.
AB  - Rubinstein-Taybi syndrome is a syndrome of mental retardation associated with
      broad thumbs and big toes. The patients have a characteristic flat face with a
      beaked nose. This paper deals with brain changes in a patient with this syndrome,
      studied by MR imaging, which mainly consist of bilateral rolandic cortical clefts
      and diminished white matter, which probably account for mental retardation.

PMID- 8734779
TI  - 3D-spiral CT of multiple exostoses.
AB  - We report pre- and post-operative three-dimensional (3D)-spiral CT images in a
      patient with multiple exostoses. Images of 3D-CT, which were performed using the
      integrated 3D software of the CT system, showed the exact shapes and locations of
      the individual tumors around the knee joint in comparison with the surgical
      findings and resected specimen. 3D-spiral CT images of multiple exostoses would
      be useful for the planning of surgical procedure.

PMID- 8734780
TI  - Isolated choroid plexus lipomas.
AB  - Seven patients with isolated choroid plexus lipomas were found during the
      consecutive evaluation of 5351 CT and 1542 MR examinations of the brain during
      approximately 9 months, from the diagnosis of the first case up to the last one.
      Five patients were adults and two were children (one neonate). The lesions were
      unilateral in six patients, and bilateral in one (the neonate). Their sizes
      ranged from 2mm to 1 cm, and they were nodular or curvilinear. The lesions were
      bright on spin-echo T1-weighted and water saturation MR images, and were dark on
      spin-echo T2-weighted and fat saturation MR images. Relatively smaller lesions
      (five cases) were not seen on the CT scan. We noted an approximately 0.04%
      frequency on the CT scan (two in 5351 CT examinations), and 0.45% frequently on
      the MR images (seven in 1542 MR examinations) for isolated choroid plexus
      lipomas.

PMID- 8734781
TI  - Abdominal aortic coarctation: CT, MRI, and angiographic correlation.
AB  - Abdominal aortic coarctation is an uncommon entity in the elderly. We present a
      case of abdominal aortic coarctation with computed tomography (CT), magnetic
      resonance imaging (MRI) and conventional angiographic correlation. CT and MR
      imaging detected an abnormal abdominal aorta distal to the origin of the celiac
      axis with the diagnosis of abdominal aortic coarctation confirmed by conventional
      angiography. Clinical presentation and diagnostic imaging findings depend on the
      level of the coarctation and its relationship to the renal vessels.

PMID- 8734782
TI  - MRI of pseudocoarctation of the aorta: morphological and cine-MRI findings.
AB  - We report a case of pseudocoarctation of the thoracic aorta diagnosed by magnetic
      resonance imaging. Morphological spin-echo findings and cine-MRI performed by
      gradient-echo multiphase images are reported. No other more invasive examinations
      were needed to establish the diagnosis of pseudocoarctation and to differentiate
      from other aortic abnormalities.

PMID- 8734783
TI  - Pineal and suprasellar metastasis of lung cancer: case report and review of the
      literature.
AB  - A very rare case of simultaneous pineal and suprasellar metastasis of lung cancer
      in a 46-year-old man is reported. Simultaneous mass lesions in these regions are
      usually diagnosed as primary germ cell tumors in the central nervous system. The
      clinical features and differential diagnosis are discussed.

PMID- 8734785
TI  - Sarcoidosis of the spinal cord with extensive vertebral involvement: a case
      report.
AB  - We report on a patient with systemic sarcoidosis who was presented with
      myelopathy and backache. Plain spinal films were normal, CT scan showed sclerotic
      lesions within the vertebrae. MRI showed more extensive involvement of the spine
      with multiple vertebral lesions which were hypointense on both T1W1 and T2W1 and
      did not enhance with gadolinium. MRI also showed high signal lesions within the
      cervical and lumbar spinal cord on T2-weighted images (T2W1) which were
      isointense on T1-weighted images (T1W1) and did not enhance. Vertebral biopsy
      results were consistent with the diagnosis of sarcoidosis. MRI is very sensitive
      in detecting sarcoidosis of bone but non-specific and other types of sclerotic or
      lytic bone lesions (notably metastases) need to be excluded.

PMID- 8734784
TI  - A 24 year follow up of an isolated lymphangioma of the kidney.
AB  - Renal lymphangioma is a rare benign tumor of the kidney. An example is presented
      which was initially identified by excretory urography, angiography and biopsy. A
      24 year follow up included computed tomography. The radiographic findings,
      pathogenesis and natural history of this unusual tumor are discussed.

PMID- 8734786
TI  - Case report: MRI of extrapancreatic gastrinoma.
AB  - Islet cell tumors are a relatively rare group of neuroendocrine tumors that are
      often difficult to image preoperatively. We present the magnetic resonance
      imaging characteristics of an uncommon and unusually large extrapancreatic
      gastrinoma.

PMID- 8734787
TI  - Stimulation of the T-cell antigen receptor-CD3 complex signaling pathway by the
      tyrosine phosphatase inhibitor pervanadate is mediated by inhibition of CD45:
      evidence for two interconnected Lck/Fyn- or zap-70-dependent signaling pathways.
AB  - The tyrosine phosphatase specific inhibitor pervanadate is a potent activator of
      T lymphocytes through induction of tyrosine phosphorylation and downstream events
      of the activation cascade. Using CD45- or CD3-negative variants of the Jurkat
      leukemic T-cell line we show that the different biochemical events induced by
      pervanadate appeared to be dependent on the presence at the cell surface of
      either CD45 or CD3. CD45-dependent events such as tyrosine phosphorylation of
      Shc, activation of nuclear factor-kappa B (NF-kappa B), activator protein-1 (AP
      1), transcription factors, and stimulation of interleukin-2 (IL-2) promoter and
      of CD69 and CD25 surface expression paralleled activation of the tyrosine kinases
      lck and fyn. By contrast, stimulation of calcium influx, a CD3-dependent event,
      paralleled zap-70 activation. The data demonstrate that the T-cell antigen
      receptor-CD3 (TcR-CD3) complex is functionally linked to two different protein
      tyrosine kinase (PTK) modules with separate specific functions and that CD45 may
      be an important regulator of this coupling.

PMID- 8734788
TI  - Interleukin-10 drives human monocytes to CD16 positive macrophages.
AB  - Cells of the monocyte/macrophage lineage are heterogenous in that some types
      express the CD16 molecule (Fc receptor for IgG, type III), while others are
      negative. We now show that culture of human blood monocytes with interleukin-10
      (IL-10) will induce high levels of cell surface CD16 within 18 hr, and this goes
      along with increased transcript levels. After prolonged culture for 36 hr,
      control cultures also become CD16 positive and this induction can be prevented by
      anti-IL-10, but not by anti-tumor necrosis factor (TNF) antibody or isotype
      control. In vitro culture of blood monocytes results in a spontaneous decrease of
      the myelomonocytic stem cell antigen CD33, suggesting that the cells undergo
      maturation. IL-10 treatment will accelerate this process and result in a further
      reduction of cell surface CD33. These data indicate that IL-10 promotes monocyte
      maturation and directs these cells to develop into CD16 positive macrophages.

PMID- 8734789
TI  - Transmembrane TNF is sufficient to induce localized tissue toxicity and chronic
      inflammatory arthritis in transgenic mice.
AB  - TNF plays a pivotal role in the pathogenesis of a broad spectrum of infectious,
      inflammatory, and autoimmune diseases. In addition to the secreted, mature 17 kD
      form, TNF exists as a bioactive precursor 26 kD transmembrane protein.
      Transmembrane TNF signaling has been directly associated with specific immune
      mechanisms, including the contact-dependent lymphocyte and monocyte-mediated cell
      killing and the CD40 ligand-independent, T cell-mediated polyclonal B cell
      activation. In previous studies, we have reported that mice expressing 3'-UTR
      modified human TNF transgenes develop chronic inflammatory polyarthritis with a
      100% phenotypic penetrance and timed disease onset. In additional experiments, we
      have also shown that high-level expression of human TNF in lymphoid cells of
      transgenic mice results in both local (thymic hypoplasia) and systemic
      (ischaemia, tissue necrosis, and wasting) TNF-mediated pathology. In this study
      we show that transgenic mice expressing a T cell-targeted membrane-associated
      mutant human TNF alpha protein are displaying only local TNF-mediated
      pathologies, ranging from lymphoid tissue derangements to proliferative synovitis
      and chronic inflammatory arthritis. These results demonstrate that in vivo, at
      least part of the pathogenic activities of TNF alpha may be assigned to the
      functioning of its uncleaved, membrane-associated form.

PMID- 8734790
TI  - Bacteria and bacterial cell wall constituents induce the production of regulatory
      cytokines in dendritic cell clones.
AB  - The primary function of dendritic cells (DC) is the uptake, processing, and
      presentation of antigens to unprimed T cells, but the regulation of these
      functions is largely unknown. The study of the signals that maintain DC in a
      resting state or that drive their activation has been hampered by the
      difficulties in obtaining pure DC populations. The availability of immortalized
      DC clones from different tissues (spleen and skin) allowed us to investigate the
      regulation of cytokine production in response to physiological signals in the
      absence of contaminating cells. The DC clones exhibited the phenotypical and
      functional features of DC precursors and could phagocytose, albeit at a low rate,
      whole bacteria. Heat-inactivated bacteria and bacterial cell wall products were
      tested for cytokine induction. Lipopolysaccharide, lipoteichoic acid, and gram
      negative bacteria were potent inducers of tumor necrosis factor alpha and
      interleukin 6 release, whereas gram-positive bacteria were less efficient. The
      results suggest that microbial infections can directly promote cytokine DC
      release of relevant inflammatory responses as well as in the autocrine activation
      of DC.

PMID- 8734791
TI  - Microtubule-active agents mimic lipopolysaccharides in priming macrophages for
      enhanced arachidonic acid metabolism.
AB  - Macrophages play a crucial role in inflammation and host defense, in part, by
      secreting metabolites of arachidonic acid (20:4). Bacterial lipopolysaccharides
      (LPS) are poor agonists of the 20:4 cascade, but do have the capacity to prime
      macrophages for greatly increased 20:4 metabolism upon subsequent stimulation
      with activators of protein kinase C (PKC). The microtubule-stabilizing agent,
      taxol, mimics many of the effects of LPS in macrophages. We demonstrate in this
      study that taxol, like LPS, primes murine peritoneal macrophages for an enhanced
      release of 20:4 in response to both phorbol 12-myristate 13-acetate (PMA) and
      zymosan. Taxol and LPS, when used at maximum concentrations, acted additively to
      prime macrophages for PMA-stimulated release of 20:4, suggesting that the two
      agents signal through different pathways. Interestingly, agents that stimulate
      the depolymerization of microtubules, colchicine and nocodazole, also primed
      macrophages for an enhanced release of 20:4 in response to PMA, however, they did
      not prime when zymosan was the stimulus. We conclude that agents that disrupt the
      microtubule network prime resident peritoneal macrophages for enhanced release of
      20:4.

PMID- 8734792
TI  - Defective translation of tumor necrosis factor mRNA in lipopolysaccharide
      tolerant macrophages.
AB  - Macrophage activation by lipopolysaccharide (LPS) results in the translational
      activation of tumor necrosis factor (TNF) mRNA. The initial phase of macrophage
      activation is followed by a refractory state called LPS tolerance characterized
      by an impaired TNF production in response to a secondary LPS challenge. LPS
      tolerant macrophages contain high amounts of TNF mRNA, suggesting a translational
      regulation of TNF biosynthesis. The induction of LPS tolerance was studied in RAW
      264.7 macrophages stably transfected with a chloramphenicol acetyl-transferase
      (CAT) reporter gene construct driven by a constitutive cytomegalovirus promoter
      and containing the 3' untranslated region of the murine TNF gene. We found that
      primary stimulation of transfected cells by LPS (1 ng/ml, 12 hr) resulted in a
      marked suppression (80%) of CAT accumulation in response to a secondary LPS
      challenge (1 microgram/ml, 6 hr). In contrast, the accumulation of CAT mRNA was
      not influenced by LPS tolerance. Using the same CAT reporter, we observed that
      the serine/threonine phosphatases 1 and 2A inhibitor okadaic acid induced TNF
      mRNA translation and that this activation was not inhibited by LPS-tolerance. In
      conclusion, these data indicate that deficient production of TNF in LPS-tolerant
      macrophages in response to a second LPS challenge is characterized by a defective
      translation of TNF mRNA. However, this hyporesponsiveness to LPS is specific,
      since translation of TNF mRNA induced by okadaic acid is not inhibited in LPS
      tolerant macrophages.

PMID- 8734793
TI  - Ankle arthrodesis: results after the miniarthrotomy technique.
AB  - Of 34 ankle fusions (34 patients) performed at our institution between June 1992
      and June 1993, 15 utilized a miniarthrotomy technique. This technique involves
      two 1.5-cm incisions, one medial and one anterolateral, through which the ankle
      joint cartilage and synovium are debrided. Subchondral bone resection is
      completed with a high-speed cutting tool, creating a "slurry" that is saved for
      local bone graft. The ankle is then appropriately positioned (5 degrees of
      valgus, 0 degree of dorsiflexion, and neutral rotation), cannulated screws are
      inserted, the position is checked fluoroscopically, and the wound is closed. The
      patient receives a short leg cast at 2 weeks and a walking cast at 3 to 5 weeks
      until there is radiographic and clinical evidence of solid arthrodesis. In our 15
      patients, follow-up ranged from 12 to 19 months after surgery and arthrodesis was
      radiographically evident at a mean of 6.0 weeks (range, 3-15 weeks).
      Complications were limited to a transient synovitis in 7/15 patients, which
      lasted approximately 3 weeks and was possibly related to the bone slurry.
      Although ankle joints with marked malalignment require a more extensive open
      arthrodesis procedure, this miniarthrotomy technique offers decreased soft-tissue
      insult, decreased bone stripping, easy application, and rapid healing time for
      the treatment of severe degenerative changes of the ankle with minimal deformity.

PMID- 8734794
TI  - Open reduction and internal fixation of type II intra-articular calcaneus
      fractures.
AB  - Open reduction and internal fixation of 23 type II calcaneus fractures in 21
      patients was performed using a standard extended lateral approach. Average follow
      up was 26 months (range, 12-47 months). The Creighton-Nebraska Health Foundation
      Assessment Score for Fractures of the Calcaneus was used to evaluate fractures.
      The average score was 91.4 (range, 80-100), which represented an excellent
      result. A series of 10 type II fractures treated with closed methods was also
      evaluated using the same evaluation methods. The average score was 70 (range, 60
      84), which represented a fair result. There was a clear statistically significant
      superiority with type II calcaneus fractures treated with open reduction and
      internal fixation (P < 0.0001). We recommend type I calcaneus fractures
      (nondisplaced) be treated with closed methods, and type II calcaneus fractures
      (displaced) be treated with open reduction and internal fixation.

PMID- 8734795
TI  - Magnetic resonance imaging of acute Maisonneuve fractures.
AB  - Magnetic resonance imaging (MRI) studies were performed on five patients with
      acute Maisonneuve fractures. All patients had sustained a twisting injury to
      their ankles and complained of ankle pain and pain over their proximal fibula.
      High quality images with excellent visualization of all the ankle ligamentous
      structures were obtained. MRI showed that the anterior inferior tibiofibular
      ligament was disrupted in all patients and the posterior inferior tibiofibular
      ligament was intact in three of five patients. Also, the anterior talofibular
      ligament was disrupted in all patients and the calcaneofibular ligament was
      ruptured in two of five patients. This raises the question of whether patients
      with Maisonneuve fractures have lateral ankle instability at long-term follow-up.
      Although the superficial deltoid ligament was disrupted in all patients, the deep
      deltoid ligament was intact in one patient, partially disrupted in one patient,
      and completely disrupted in three patients. The interosseous ligament was
      disrupted at the ankle in all patients, while the interosseous membrane was
      disrupted in the leg in all patients except one. This patient had an intact
      interosseous membrane despite rupture of the interosseous ligament at the ankle
      and the presence of a proximal one third fibula fracture.

PMID- 8734796
TI  - Clinical results of simultaneous adjacent interdigital neurectomy in the foot.
AB  - Fifteen patients (19 feet) who underwent simultaneous surgical excision of two
      primary interdigital neuromas in adjacent web spaces of the foot were studied
      retrospectively. There were 11 female patients (73%). The average age of the
      patients was 54.4 years. Other causes of multiple web space tenderness were
      excluded prior to surgical resection of both neuromas. At an average follow-up of
      68.6 months (range, 32-113 months), 10 feet (53%) had complete resolution of
      symptoms and six feet (31%) had minimal residual symptoms. Three feet in two
      patients (16%) continued to have significant pain after surgery. One sequela of
      the procedure was dense sensory loss of the plantar aspect of the third
      metatarsal head to the tip of the third toe. There was also proximal dorsal
      sensory loss to the second, third, and fourth toes which was a function of the
      type of incision used. The sensory loss did not cause disability in the patients,
      but did cause some awkwardness with nail care. Resection of adjacent interdigital
      neuromas, although rarely indicated, can be expected to provide significant pain
      relief in 84% of patients, which is similar to results reported for resection of
      a single neuroma.

PMID- 8734797
TI  - Tibiotalar contact area and pressure distribution: the effect of mortise widening
      and syndesmosis fixation.
AB  - An unconstrained cadaver ankle model was designed to reevaluate the effect of
      ankle mortise widening and syndesmotic fixation on the load-bearing
      characteristics of the tibiotalar joint. Tibiotalar contact area, centroid shift,
      and mean contact pressure were quantified using a pressure-sensitive film
      technique. Six fresh-frozen below-knee amputation specimens were axially loaded
      with 500 N in three positions: neutral, 10 degrees of dorsiflexion, and 20
      degrees of plantarflexion. The tibiotalar contact area and centroid position for
      each specimen in its intact state were first determined and then compared with
      values obtained after syndesmotic fixation, mortise widening of 2 and 4 mm, and
      deep deltoid ligament transection. Syndesmotic fixation significantly decreased
      joint contact area but did not consistently affect centroid position. However,
      unlike earlier studies, which used more constrained ankle fracture models,
      mortise widening with or without deltoid rupture was not found to significantly
      affect contact area, centroid position, or joint contact pressure. When
      statically loaded, the talus moved to its position of maximal congruence in the
      mortise, rather than displacing laterally along with the lateral malleolus.

PMID- 8734798
TI  - Osteonecrosis of the talus: treatment by hindfoot fusion.
AB  - The results were reviewed for 11 ankles (10 patients) that had been treated with
      various hindfoot arthrodeses because of symptomatic osteonecrosis of the talus.
      Follow-up averaged 6.5 years (range, 2-15 years). A functional assessment using a
      modified Mazur grading system was performed both before surgery and at final
      follow-up. Data were also collected on the duration of the procedure,
      intraoperative findings, and the patient's assessment of postoperative cosmesis
      (excellent, good, fair, or poor). Radiographs were analyzed to determine the
      interval from the procedure until bony union. Nine of the 11 arthrodeses (82%)
      fused with the primary procedure and achieved excellent Mazur ratings (mean, 86
      points; range, 81-90 points). The average interval until radiographic fusion was
      7 months (range, 4-13 months). All eight patients (nine fusions) with successful
      fusions graded their cosmetic outcomes as excellent or good. The average length
      of the procedure was 148 minutes (range, 130-300 minutes), compared with an
      average of 92 minutes (range, 62-151 minutes) for ankle arthrodeses performed by
      the same surgeons in rheumatoid or osteoarthritic ankles (P < 0.001) and 102
      minutes (range, 75-164 minutes) from a report in the literature. Two of the
      procedures were complicated by nonunions secondary to infections. In one patient,
      after treatment by debridement and intravenous antibiotics, reinfection and
      chronic osteomyelitis developed with a subsequent below-knee amputation. The
      other patient was treated successfully with debridement, antibiotics, and
      subsequent revision arthrodesis, which fused solidly at 9 months with an
      excellent result. We conclude that hindfoot arthrodeses for osteonecrosis can be
      technically demanding, but, despite having a long time to bony union, they can
      have an excellent clinical outcome.

PMID- 8734799
TI  - Multiple lower limb osteophytosis with macrodactyly: a case report.
AB  - A 39-year-old woman with restriction of movement and macrodactyly of the great
      toes was found to have severe juxta-articular multiple osteophytosis of the lower
      limbs. The pathogenesis of this unusual condition is unknown. It may be a variant
      of diffuse idiopathic skeletal hyperostosis.

PMID- 8734800
TI  - Tarsal coalition.
AB  - Tarsal coalition is a bridging between the tarsal bones of the foot. The bridge
      may be composed of bone, cartilage, fibrous tissue, or a combination of these.
      When symptomatic, patients usually present with hindfoot pain and frequent
      sprains as children, adolescents, or young adults. The classical appearance is a
      rigid flatfoot with heel valgus and abduction of the forefoot. Flexible cavus
      feet have been reported. The incidence in the general population is less than 1%,
      and the most common types are talocalcaneal and calcaneonavicular coalitions. The
      cause is attributed to failure of segmentation and differentiation of the
      primitive mesenchyme. Calcaneonavicular coalitions can be diagnosed with an
      oblique radiograph of the hindfoot. Most talocalcaneal coalitions require
      computerized tomography for diagnostic confirmation. Magnetic resonance Imaging
      may be useful for cartilaginous and fibrous coalitions. Casting is the usual
      initial treatment for the symptomatic individual. With treatment failure, in the
      absence of degenerative changes, resection of the coalition can be performed with
      good results. Isolated subtalar fusion may be performed for failed talocalcaneal
      resections. Failed subtalar fusions and failed calcaneonavicular resection may be
      treated with triple arthrodesis.

PMID- 8734802
TI  - Assessment of serum levels of alpha-1-microglobulin, beta-2-microglobulin, and
      retinol binding protein in the fetal blood. A method for prenatal evaluation of
      renal function.
AB  - The concentrations of alpha-1-microglobulin, beta-2-microglobulin, and retinol
      binding protein were determined in fetal blood sampled by cordocentesis. The
      blood values of 126 fetuses without ultrasonographic findings of urinary tract
      abnormalities as controls were found to be independent of the week of gestation.
      In nine fetuses affected by a severe bilateral renal dysplasia or agenesis,
      elevated values of alpha-1-microglobulin but normal values of retinol binding
      protein were obtained. The authors recommend the determination of alpha-1
      microglobulin and, with some restriction, also of beta-2-microglobulin in
      prenatal renal function diagnosis.

PMID- 8734801
TI  - Development of a model system to compare cell separation methods for the
      isolation of fetal cells from maternal blood.
AB  - Three major methods have been described for the isolation of fetal cells from
      maternal blood: fluorescence-activated cell sorting (FACS), immunomagnetic beads,
      and magnetic-activated cell sorting (MACS). To date, no study has directly
      compared fetal cell recovery using each of these methods. Here we describe our
      system using a "model' male fetal cell mixed into female peripheral blood
      mononuclear cells. Fetal cell yields and purities were assayed by a quantitative
      polymerase chain reaction (qPCR) using chromosomes Y- and 7-specific sequences.
      Fetal cell recovery was investigated by selection of CD71+ cells or depletion of
      CD45+ cells. Our data demonstrated variation in fetal cell recovery for all
      methods tested, although CD71+ selection by FACS gave the best and most
      consistent results.

PMID- 8734803
TI  - Early amniocentesis at 10-12 weeks' gestation.
AB  - In this study we report the results of 181 ultrasound-guided genetic
      amniocenteses performed at 10-12 weeks of gestation and describe the indication,
      technical problems, amniotic fluid volume, culture success and timing, abortion
      and fetal loss rate, and perinatal results. Amniotic fluid was obtained in 98.4
      per cent of the cases; at the first attempt, in 167 out of 181. The culture
      success rate was 94.5 per cent, and the fetal loss rate within 2 weeks was 0.5
      per cent (one case with a sonographic abnormality). The total fetal loss rate
      during pregnancy was 1.6 per cent. A comparison of our data and those of other
      published series shows no significant differences, either with respect to this
      period of gestation (10-12 weeks) or with respect to the traditionally called
      early amniocentesis' (12-14 weeks) or conventional amniocentesis (15 weeks or
      more). The mean culture time was just a few days longer in some of the series,
      and in some cases, there was also a lower success rate after culture,
      particularly when amniocentesis was carried out at 10 weeks or less. We conclude
      that amniocentesis performed at 10-12 weeks is feasible, safe, and easy to
      perform, and provides a real benefit to the pregnant woman.

PMID- 8734804
TI  - Measurement of amniochorionic membrane thickness using high-frequency ultrasound.
AB  - Premature rupture of the membranes (PROM) accounts for approximately 30 per cent
      of all preterm deliveries. PROM is thought to be mainly due to a decrease in
      membrane integrity. The aim of our investigation was to determine, post-partum
      after 28 normal deliveries, the thickness of the amniochorionic membrane using a
      20 MHz high-frequency ultrasound. The data obtained were compared with
      histological sections for measurement accuracy using a linear regression analysis
      method. The membrane thickness of the total study group was 0.83 +/- 0.11 mm
      (0.72-1.08 mm). Based on a statistical comparison with the histological sections,
      the high-frequency ultrasound examination was shown to be highly reliable, with a
      correlation coefficient of r = 0.96 (P < 0.0001). High-frequency ultrasonographic
      examinations of membrane thickness are an objective and reliable method and may
      be a gain to prenatal diagnostics once this method can be used in vivo.

PMID- 8734805
TI  - Effect of gravidity on maternal serum markers for Down's syndrome.
AB  - The effect of gravidity on maternal serum alpha-fetoprotein (AFP), unconjugated
      oestriol (uE3), and human chorionic gonadotrophin (hCG) levels was investigated
      in 27,592 women being screened for Down's syndrome. There was no difference in
      the median AFP level in primigravid and multigravid women, but the median hCG
      level in multigravid women was 5.9 per cent lower than in those tested in their
      first pregnancy (P < 0.0001) and the median uE3 level was 3.9 per cent lower (P <
      0.0001). Among multigravid women, there was no material difference in hCG levels
      according to the number of previous pregnancies or livebirths, whereas uE3 levels
      declined steadily with increasing numbers. Both markers declined with advancing
      maternal age: for hCG this was an independent effect, but for uE3 it was due to
      the correlation between age and gravidity. Allowing for these effects will not
      greatly alter the Down's syndrome screening detection and false-positive rates.

PMID- 8734806
TI  - Prenatal diagnosis of uniparental disomy 15 following trisomy 15 mosaicism.
AB  - Maternal uniparental disomy 15 (UPD15), responsible for approximately 25 per cent
      of Prader-Willi syndrome cases, is usually caused by maternal meiosis I non
      disjunction associated with advanced maternal age. These cases may initially be
      detected as mosaic trisomy 15 during routine prenatal diagnostic studies. In such
      cases, PCR (polymerase chain reaction) microsatellite analysis of uncultured
      cells makes prospective prenatal diagnosis for UPD15 possible with results
      available in 2-4 days. We have performed molecular analyses on a series of seven
      cases of mosaic trisomy 15 identified in amniotic fluid (AF, n = 3) or chorionic
      villus samples (CVS, n = 4) from patients initially referred for advanced
      maternal age or abnormal triple screen. In all cases, the maternal ages were > or
      = 35 years and maternal meiosis I non-disjunction was documented as the cause of
      the trisomy in all informative cases (n = 5). Of the three case with mosaic
      trisomy 15 at amniocentesis, two showed the presence of the trisomy in the fetus.
      Molecular analysis showed one case with maternal UPD15 in the euploid cell line
      and one case with biparental inheritance. Both of these families elected to
      terminate the pregnancies based on the presence of true fetal mosaicism. In the
      third case, low-level trisomy 15 mosaicism in the amniotic fluid was not
      confirmed in a follow-up amniotic fluid sample and molecular analysis indicated
      biparental inheritance in the fetus. For the four trisomy 15 mosaics detected at
      CVS, molecular analysis was performed on direct amniotic fluid cell lysates for
      prospective diagnosis of UPD at 14-16 weeks' gestation. Follow-up cytogenetic
      analysis of the amniotic fluid in all four cases was normal, indicating confined
      placental mosaicism. Molecular analysis showed one of these four cases to have
      maternal heterodisomy 15. Based on the likelihood of Prader-Willi syndrome due to
      maternal UPD15, the couple chose to terminate the pregnancy. The total of two of
      seven cases of trisomy 15 mosaicism resulting in UPD15 is consistent with the
      theoretical expectation of one-third and indicates a high risk of UPD in such
      pregnancies. Therefore, UPD testing should be offered in all cases of mosaic
      trisomy 15 encountered in CVS or amniocentesis.

PMID- 8734808
TI  - Prenatally detected hepatic hamartoma: another cause of non-immune hydrops.
AB  - Although various conditions associated with non-immune hydrops have been
      reported, primary hepatic tumours are rare. As a mesenchymal hamartoma of the
      liver is a rare benign tumour, it has not been listed as a cause of hydrops. In
      this report we describe a case in which a large cystic mass in the fetal liver
      associated with non-immune hydrops was prenatally detected with sonography and
      magnetic resonance imaging, and histopathologically confirmed as a mesenchymal
      hamartoma of the liver.

PMID- 8734807
TI  - Molecular prenatal diagnosis of glycogen storage disease type Ia.
AB  - Glycogen storage disease type Ia (GSD Ia, von Gierke disease) is an autosomal
      recessive inborn error of metabolism caused by the deficiency of D-glucose-6
      phosphatase (G6Pase). Since this enzyme is expressed primarily in hepatocytes,
      couples at risk for GSD type Ia relied on fetal liver biopsy for prenatal
      diagnosis. The recent isolation of the G6Pase gene and identification of several
      disease-causing mutations have permitted molecular prenatal diagnosis using
      amniocytes or chorionic villi. Chorionic villus sampling (CVS) was performed in
      an Ashkenazi Jewish family in whom a previous child was homoallelic and both
      parents were heterozygous for the R83C mutation. Molecular analysis revealed that
      the fetus was not affected. The prenatal diagnosis was confirmed postnatally by
      biochemical and molecular studies. Thus, the molecular prenatal diagnosis of GSD
      type Ia can be safely and accurately made in the first trimester.

PMID- 8734809
TI  - Fetal hydrops secondary to human parvovirus infection in early pregnancy.
AB  - Parvovirus B19 infection has been associated with fetal anaemia, hydrops, and in
      some cases demise. Most of the reported cases of fetal hydrops were detected in
      second-trimester fetuses. We report a series of three cases in which human
      parvovirus infection was associated with hydropic changes at an earlier
      gestational age. Spontaneous resolution of hydrops occurred in all fetuses. A
      greater understanding of the natural history of human parvovirus infection is
      needed prior to deciding on the mode of therapy (conservative management versus
      in utero fetal therapy).

PMID- 8734810
TI  - Early prenatal diagnosis of Fanconi anaemia in a twin pregnancy, using DNA
      analysis.
AB  - We present a case of prenatal diagnosis of Fanconi anaemia (FA) in a pair of
      twins at 14 weeks of gestation. The parents had previously had two children: a
      healthy boy and a boy with FA belonging to complementation group C (FAC). The FA
      patient is a compound heterozygote, carrying a 322delG and a IVS4+4A-->T mutation
      in the FAC gene. Prenatal DNA analysis showed that both fetuses were heterozygous
      for different mutations in the FAC gene. Both fetuses had normal male karyotypes.
      At 36 weeks the twins were born. They did not show congenital anomalies.

PMID- 8734812
TI  - The vanishing fetal ureterocele: a cause for concern?
AB  - The natural history of fetal ureteroceles is poorly understood. We report two
      cases of fetal ureterocele which add to our understanding of its natural history.
      In both cases, the fetal ureterocele 'resolved' later in gestation. The postnatal
      findings emphasize the importance of an aggressive newborn evaluation despite
      apparent resolution of the ureterocele on prenatal ultrasound examination.

PMID- 8734811
TI  - Prenatal diagnosis of Blackfan-Diamond syndrome: case report and review of the
      literature.
AB  - A case of prenatally diagnosed autosomal dominant congenital hypoplastic anaemia
      (Blackfan-Diamond syndrome or Aase congenital anaemia) causing hydrops fetalis is
      presented. Recommendations for the prenatal management of Blackfan-Diamond
      syndrome (BDS) include prepregnancy counselling for parents with BDS, detailed
      and serial fetal ultrasonography and echocardiography, cordocentesis if there are
      signs of anaemia, consideration of in utero transfusions and planned early
      delivery if the fetus is affected.

PMID- 8734813
TI  - Prenatal aspects of giant fetal cranial haemangio-endothelioma.
AB  - A case of a large vascular lesion of the skull is reported. The lesion was
      discovered at 22 weeks' gestation and it rapidly increased in size, reaching 8 cm
      a month later. Tumor echogenicity was the same as that for soft tissues and
      colour Doppler examination revealed intense vascularization. Cordocentesis showed
      features of the Kasabach-Merritt syndrome and very high plasma levels of alpha
      fetoprotein. A Caesarean section was performed to avoid dystocia and led to the
      birth of a baby with cardiac failure in the immediate neonatal period. Biopsies
      of the mass led to the diagnosis of a non-malignant haemangio-endothelioma. The
      mass was removed and plastic surgery performed. The baby is alive and well 9
      months after the operation.

PMID- 8734814
TI  - Early sonographic findings suggestive of the human fetal tail.
AB  - The prenatal diagnosis of a human tail was suggested in six fetuses with
      ultrasound findings of an echogenic protrusion in the lumbo-sacral region. All
      fetuses were at 14-16 weeks' gestation. The ultrasound findings disappeared in
      all cases at 22-23 weeks. Dermal abnormalities such as pilonidal sinus, deep
      dimples, and scarred tissue were found in all six newborns. It is possible that
      the late regression of the embryonic human tail was the cause of these dermal
      findings.

PMID- 8734815
TI  - Prenatal detection of de novo inversion of chromosome (2) (p13q11.2) and
      postnatal follow-up.
AB  - We report the first case of an apparent de novo pericentric inversion of
      chromosome 2 at the breakpoints p13q11.2 that was detected prenatally. Follow-up
      performed over 4 years showed phenotypic abnormalities including minor
      craniofacial dysmorphism, hypotonia, hearing loss, gustatory flushing syndrome,
      and severe developmental delays. The literature on chromosome 2 inversion is
      reviewed.

PMID- 8734816
TI  - The presence of hydrops fetalis in a fetus with congenital mesoblastic nephroma.
AB  - We report the first prenatal diagnosis of a case of congenital mesoblastic
      nephroma complicated by hydrops fetalis. Congenital mesoblastic nephroma is
      generally thought to be a benign disease but when complicated by hydrops fetalis
      it may be a potentially lethal condition.

PMID- 8734817
TI  - A case of maternal uniparental disomy of chromosome 9 in association with
      confined placental mosaicism for trisomy 9.
AB  - We describe the first case of maternal uniparental disomy (UPD) of chromosome 9
      in a fetus who was shown to have mosaic trisomy 9 in a chorionic villus sample.
      Karyotyping and molecular studies following termination of the pregnancy
      confirmed mosaicism in the placenta and maternal UPD(9) in the fetal tissues.
      This case demonstrates that the mechanism of trisomy correction may result in a
      fetus with UPD(9).

PMID- 8734818
TI  - Alpha-fetoprotein elevation in maternal serum after percutaneous umbilical blood
      sampling (PUBS)

PMID- 8734820
TI  - Current awareness in prenatal diagnosis.

PMID- 8734819
TI  - Triploidy, imprinting, and hCG levels in maternal serum screening.

PMID- 8734821
TI  - Cancer registries in epidemiologic research.

PMID- 8734822
TI  - Dioxin and cancer: the never-ending story.

PMID- 8734823
TI  - A program for eradication of hepatitis B from Taiwan by a 10-year, four-dose
      vaccination program.
AB  - Approximately 15 percent of the Taiwanese population are chronic carriers of
      hepatitis B virus (HBV), among the highest rates in Asia. In July 1984, the
      Taiwanese government initiated a nationwide HBV-vaccination program. The program
      began with educational efforts and voluntary prenatal screening for HBsAg.
      Infants of HBsAg-carrier mothers received a four-dose regimen of hepatitis B
      vaccine. Those born to highly infectious mothers also received a dose of
      hepatitis-B immune globulin within 24 hours after birth. Seroepidemiologic
      studies were conducted using a random sample of infants. Serum samples were
      collected at 18, 24, 36, and 48 months and analyzed via radioimmunoassay for
      HBsAg, anti-HBs, and anti-HBc. Infants of highly infectious mothers had HBsAg
      positivity rates of 14.2 percent (vaccine plus HBIG) and 19.7 percent (vaccine
      only) when on schedule, and 17.0 percent when off schedule. Infants of moderately
      infectious mothers had an HBsAg positivity rate of 3.0 percent when on schedule
      and 6.4 percent when off schedule. These low positivity rates persisted
      throughout the 48-month follow-up period. This represents a dramatic improvement
      upon the 40 to 96 percent vertical transmission rate seen before the program
      implementation. This program demonstrates that mass immunoprophylaxis for HBV is
      feasible, and provides practical strategies for other Asian countries.

PMID- 8734824
TI  - Cancer mortality in German male workers exposed to phenoxy herbicides and
      dioxins.
AB  - In an occupational cohort study, the relation between exposure to phenoxy
      herbicides, and contaminants (dioxins and furans) and cancer mortality was
      investigated. A total of 2,479 workers from four plants in Germany were included,
      with a mortality follow-up until the end of 1989 (for one cohort, until the end
      of 1992). A total of 484 deaths were recorded yielding a standardized mortality
      ratio (SMR) of 101 (95 percent confidence interval [CI] = 92-111) for total
      mortality, and an SMR of 119 (CI = 100-141) for all malignant diseases. A variety
      of herbicides was produced, including those which are known to have been
      contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). High dioxin and
      furan exposure (in particular, exposure to TCDD, but also to higher chlorinated
      dioxins) had occurred in two of the four plants as shown by blood-fat
      measurements in a sample of workers. Mortality from all neoplasms increased with
      latency and was highest in the largest plant where the highest TCDD blood levels
      were recorded. An increased mortality in the total cohort from respiratory cancer
      (SMR = 154, CI = 115-202), cancer of the buccal cavity and pharynx (SMR = 295, CI
      = 135-560), and non-Hodgkin's lymphoma (SMR = 326, CI = 119-710) was observed.
      Our findings are consistent with results from other cohorts which showed an
      increased overall cancer mortality and mortality of respiratory cancer after long
      term exposure to these phenoxy herbicides and dioxins.

PMID- 8734825
TI  - Determinants of survival following the diagnosis of esophageal adenocarcinoma
      (United States).
AB  - The rapidly rising incidence of esophageal adenocarcinomas in the United States
      and western Europe remains unexplained. Most persons who develop the disease have
      had long-standing gastroesophageal reflux symptoms with concomitant Barrett's
      metaplasia. They are, therefore, potentially identifiable for endoscopic
      screening and cancer surveillance, which should facilitate the early detection of
      these tumors. We undertook these analyses to determine the extent to which the
      opportunity for early diagnosis and treatment of esophageal adenocarcinomas has
      been realized in the US. Specifically, using data from the Surveillance,
      Epidemiology, and End Results (SEER) program of the US National Cancer Institute,
      we examined changes in stage of disease at diagnosis and in survival between 1973
      and 1991 and investigated patient characteristics as predictors of survival.
      Improvements in stage at diagnosis and in survival between 1973 and 1991 were
      minor and clinically insignificant; overall five-year survival never exceeded 10
      percent. Stage of disease at diagnosis was the strongest determinant of
      subsequent survival; five-year survival with patients with in situ tumors was
      68.2 percent. This survival advantage persisted up to 15 years after diagnosis
      and was independent of other prognostic factors. We conclude that the opportunity
      for reduction in esophageal cancer mortality has been largely unrealized in the
      US. In light of the increasing incidence of esophageal adenocarcinoma, efforts
      should be devoted to identifying those at highest risk of developing Barrett's
      metaplasia and subsequent adenocarcinoma, and to developing cost-effective
      primary prevention and cancer surveillance methods targetting them.

PMID- 8734826
TI  - Differences between black and white patients with cancer of the uterine corpus in
      interval from symptom recognition to initial medical consultation (United
      States).
AB  - To determine whether Black women with symptoms of uterine corpus cancer had
      longer times from symptom recognition to initial medical consultation than did
      White women in the United States, 331 newly diagnosed patients living in Atlanta
      (GA), New Orleans (LA), and San Francisco/Oakland (CA) during 1985-87 were
      interviewed to collect information on symptoms, dates of recognition and
      consultation, and other factors that might affect the interval. Data were
      analyzed to estimate medical consultation rates and rate ratios following symptom
      recognition. Median recalled times between symptom recognition and consultation
      were 16 days for Black women and 14 days for White women. Although poverty,
      having no usual source of healthcare, and other factors were associated with
      lower consultation rates, the adjusted rate among Black women was only somewhat
      lower (0.87) than among White women, and the 95 percent confidence interval (CI =
      0.58-1.31) was consistent with no true difference between the races. In addition,
      the median time to consultation for women with stage IV cancer was only 15 days
      longer than the time (14 days) for the women with stage I cancer. These results
      suggest that time from symptom recognition to initial medical consultation does
      not contribute importantly to the more advanced stage cancer of the uterine
      corpus commonly found among Black women.

PMID- 8734827
TI  - Second primary cancers following cancers of the kidney and prostate in New South
      Wales (Australia), 1972-91.
AB  - Data from the New South Wales (NSW) (Australia) Central Cancer Registry for the
      period 1972-91 were examined to determine the risk of second primary cancers
      following an initial invasive cancer of the renal parenchyma (ICD-9 code 189.0),
      renal pelvis (code 189.1), or prostate (code 185). Eligible cases were restricted
      to those who had survived for at least two months after diagnosis of the first
      primary cancer. Expected numbers of cancers were obtained by assuming that
      subjects experienced the same cancer incidence as prevailed in the corresponding
      general population and applying gender-, age-, and calendar-specific rates to the
      appropriate person-years at risk. The relative risk (RR) of a second primary
      cancer was taken to be the ratio of observed to expected numbers of second
      cancers. Following prostatic cancer, there was an overall deficit of cancers at
      all sites combined (RR = 0.79, 95 percent confidence interval [CI] = 0.75-0.84),
      and no site had a significantly raised RR. Taking this into consideration, there
      appeared to be a reciprocal relationship of increased risk of prostatic cancer
      (RR = 1.7, CI = 1.2-2.3) following an initial cancer of the renal parenchyma and
      of renal parenchymal cancer (RR = 1.2, CI = 0.8-1.7) after cancer of the
      prostate. An increased risk of bladder cancer occurred following renal
      parenchymal (RR = 3.4, CI = 1.1-8.0, for women only) as well as after renal
      pelvic cancer (men: RR = 8.7, CI = 5.4-13; women: RR = 39, CI = 26-56). A tobacco
      related pattern of excess risk was seen after renal pelvic cancer but not after
      cancer of the renal parenchyma. These data illustrate that an excess of second
      primary cancers may reflect shared etiologic factors or increased medical
      surveillance.

PMID- 8734828
TI  - Liver cancer in Asian migrants to the United States and their descendants.
AB  - The incidence of primary liver cancer in Chinese, Japanese, and Filipino migrants
      to the United States and their descendants is compared with that of United States
      born Whites. Incident liver cancer cases were ascertained between 1973 and 1986
      from population-based cancer registries serving the San Francisco/Oakland (CA)
      metropolitan area, 13 counties of western Washington, and Hawaii. The population
      of these three areas, with regard to age, race, and country of birth, was
      estimated from a special tabulation of the 1980 US census. Rates of primary liver
      cancer were higher for men born in Asia than Asian men born in the US, who, in
      turn, had higher rates than did US Whites (respective annual rates per 100,000:
      Chinese, 26.5 and 9.8; Japanese, 16.5 and 6.6; Filipinos, 11.4 and 6.5; US
      Whites, 3.4). Among Asian American women, the trends were not as consistent
      (respective annual rates per 100,000: Chinese, 2.2 and 3.7; Japanese, 1.9 and
      1.4; Filipino, 2.6 and 0; US Whites, 1.1). In general, liver cancer incidence
      among Asian Americans was lower than among residents of Asia. These findings are
      compatible with substantial variation among Asians in the prevalence of one or
      more etiologic factors for liver cancer, such as hepatitis-B infection and
      aflatoxin consumption, in relation to residence and place of birth.

PMID- 8734829
TI  - Reproductive variables and risk of uterine cervical cancer in Norwegian registry
      data.
AB  - The influence of reproductive variables on cervical cancer incidence, controlling
      for other sociodemographic factors, was estimated in Norwegian register and
      census data, using Poisson regression models. Among the 1.3 million women under
      observation, a total of 2,870 cases of cervical cancer were diagnosed. According
      to models restricted to parous women, parity level had no independent impact on
      cervical cancer incidence, but a clear effect of age at first birth was noted. It
      was most pronounced in the squamous cell carcinomas, where the incidence was
      reduced by 48 percent from age at first birth < 21 years to age at first birth
      27+ years. Women without children had the same cervical cancer incidence as
      parous women with a first birth after age 24. The sociodemographic variables
      controlled for exerted a strong net effect on the cervical cancer incidence.
      Educational level was related inversely to the cancer risk. Moreover, an
      increased risk was seen for women who had given birth when they were still single
      (never married) and for those who were divorced/separated at the time of the last
      previous census. A fairly small excess risk was found to be associated with
      living in non-rural compared with rural areas.

PMID- 8734830
TI  - Anthropometric measures and metabolic rate in association with risk of breast
      cancer (United States).
AB  - To investigate whether cancer risk-reduction seen in calorie-restricted animals
      also applies to breast cancer in women, we have analyzed data from the first
      National Health and Nutrition Examination Survey in the United States and
      subsequent follow-up surveys. During the follow-up of one to 155 months, 182 out
      of 7,622 women developed breast cancer. Due to biased under-reporting of dietary
      intake, the analysis did not examine calorie intake as an exposure variable, but
      rather focused on anthropometric measures and metabolic rate as biomarkers of
      nutritional balance. Multiple Cox regression analysis showed elevated odds ratios
      (OR) for height, elbow width, and skinfolds among postmenopausal women. ORs for
      the fifth quintile were 2.0 (95 percent confidence interval [CI] = 1.0-3.8), 2.3
      (CI = 1.2-4.7), and 2.0 (CI = 1.0-4.0), respectively. Weight (OR = 2.5, CI = 1.2
      5.1) and resting metabolic rate (OR = 2.0, CI = 1.0-4.0) were significant
      relative to the second quintile. Bitrochanteric breadth, sitting height, body
      fat, body mass index, or combination variables were not associated with cancer
      risk. It was concluded that in the analysis of breast cancer data, skeletal
      measures ought to be considered as routine potential confounders, and that using
      measured rather than estimated metabolic rates may improve risk prediction.

PMID- 8734831
TI  - The impact of smoking habits on lung cancer risk: 28 years' observation of 26,000
      Norwegian men and women.
AB  - While factory-made cigarettes dominate the market in most countries, the use of
      handrolled cigarettes accounts for a substantial proportion of the tobacco
      consumption in Norway. In the present study, we examined the impact of tobacco
      smoking on lung cancer in general, and the effect of handrolled cigarettes in
      particular. The data used was from a self-administered mailed questionnaire which
      included questions about smoking habits and which was completed by about 26,000
      men and women in 1964-65. During the follow-up from 1966 to 1993, 333 lung
      cancers in men and 102 in women were registered. The analysis was performed by
      use of the Cox proportional hazards regression models. A clear dose-response
      relationship was found both for cigarette smoking, and for pipe smoking (in men).
      The dose-response relationship of cigarette smoking was seen in all the three
      histologic groups considered-squamous cell carcinoma, adenocarcinoma, and small
      cell carcinoma. The highest relative risks were noted in squamous cell and small
      cell carcinoma. A higher risk of lung cancer was found for cigarette-smoking
      women who started cigarette smoking before the age of 30 compared with similar
      groups of men. In a combined analysis of men and women, an elevated relative risk
      of 1.9 (95 percent confidence interval = 1.2-3.3) was found for those smoking
      only handrolled cigarettes compared with those smoking factory-made filter
      cigarettes only.

PMID- 8734832
TI  - Cancer incidence among male railway engine-drivers and conductors in Sweden, 1976
      90.
AB  - During recent years, the relationship between exposure to magnetic fields and
      cancer has attracted increasing interest. In Sweden, train personnel are exposed
      to comparatively strong magnetic fields in their work. The aim of the present
      study was to investigate cancer incidence, particularly leukemia and brain
      tumors, among male railway engine drivers and conductors, respectively, and to
      compare their cancer incidence with that of the general male population. The
      study population comprised all male railway engine drivers (n = 7,466) and
      conductors (n = 2,272) who were ever employed at the Swedish State Railways
      during the period 1976-90. The study population was observed with regard to
      cancer incidence by means of the National Cancer Register for the period 1976-90.
      The total cancer incidence (all tumors included) among railway engine drivers was
      lower than in the general Swedish population. An increased incidence of
      lymphocytic leukemia was observed among railway engine drivers and conductors
      combined (relative risk = 2.3; 95 percent confidence interval = 1.3-3.2), with
      the same point estimate for both occupational groups. For brain tumor
      (astrocytoma), the observed relative risk was close to one. The study provides
      evidence of an excess risk of lymphocytic leukemia in railway engine drivers and
      conductors, workers with known occupational exposure to magnetic fields.

PMID- 8734833
TI  - A population-based study of contralateral breast cancer following a first primary
      breast cancer (Washington, United States)
AB  - To evaluate predictors of contralateral breast cancer risk, we examined data from
      a nested case-control study of second primary cancers among a cohort of women in
      western Washington (United States) diagnosed with breast cancer during 1978
      through 1990 and identified through a population-based cancer registry. Cases
      included all women in the cohort who subsequently developed contralateral breast
      cancer at least six months after the initial diagnosis, but prior to 1992 (n =
      234). Controls were sampled randomly from the cohort, matched to cases on age,
      stage, and year of initial breast cancer diagnosis. Information on potential risk
      factors for second primary cancer was obtained through medical record
      abstractions and physician questionnaires. Women who were postmenopausal due to a
      bilateral oophorectomy (i.e., a surgical menopause) at initial breast cancer
      diagnosis had a reduction in contralateral breast cancer risk compared with
      premenopausal women (matched odds ratio [mOR] = 0.25, 95 percent confidence
      interval [CI] = 0.09-0.68), whereas no reduction in risk was noted among
      postmenopausal women who had had a natural menopause (mOR = 0.90, CI = 0.39
      2.09). Among postmenopausal women, there was a suggestion of a lower risk
      associated with relatively high parity (2+). A family history of breast cancer
      was associated with an increased risk (mOR = 1.96, CI = 1.22-5.15) and varied
      little by menopausal status. Having an initial tumor with a lobular component
      (c.f. a ductal histology) was not related strongly to risk (mOR = 1.47, CI = 0.79
      2.74). The results of the present and earlier studies argue that we have limited
      ability to predict the occurrence of a contralateral breast tumor. Better
      predictors will be required before diagnostic and preventive interventions can be
      targeted to subgroups of patients with unilateral breast cancer.

PMID- 8734835
TI  - The effect of ethanol and calcium channel antagonists on rabbit EEG.
AB  - The influence of nifedipine, verapamil, and cinnarizine on the effect of ethanol
      on EEG of rabbits (frontal cortex, hippocampus, MRF) was tested. Nifedipine (1.75
      mg/kg, IP) and cinnarizine (7.5 mg/kg, IP) were given 30 min before ethanol
      administration. Verapamil (0.2 mg/kg, IV) was given 15 min before ethanol
      injection in a dose of 0.8 g/kg IV. Ethanol caused the increase of the
      frequencies 0.5-4 cps in the recording, as well as a marked decrease of the
      fastest frequencies. Verapamil prevented ethanol's effect on EEG recording.
      Cinnarizine antagonized this action to a smaller extent and the influence of
      nifedipine is transitory and less pronounced.

PMID- 8734834
TI  - Sexual, reproductive, and other risk factors for adenocarcinoma of the cervix:
      results from a population-based case-control study (California, United States)
AB  - The incidence of adenocarcinoma of the cervix increased steadily in young women
      in the United States between the early 1970s and the mid-1980s. Despite this
      increase, little is known about the etiology of this cancer, although a role for
      risk factors for both squamous cell carcinoma of the cervix and endometrial
      adenocarcinoma has been suggested. Incident cases of adenocarcinoma of the cervix
      diagnosed in women born after 1935 (ages 42 to 56 at diagnosis) were identified
      from the Los Angeles (California) County Cancer Surveillance Program (LACCSP).
      Data from personal interviews with 195 cases and 386 controls (matched on age,
      race, and neighborhood) were analyzed. Compared with women in the highest
      categories of education and income, women in the lowest categories had a 2.5 and
      3.1-fold elevated risk of adenocarcinoma of the cervix. Number of sexual
      partners, especially before age 20, was strongly predictive of risk (odds ratio =
      5.6, 95 percent confidence interval = 1.4-22.0 for 10 or more compared with no
      partners before age 20). Smoking was not associated significantly with risk.
      Weight gain and long-term use of oral contraceptives increased risk, while long
      term diaphragm use was protective. This study suggests that both sexual and
      hormonal factors are important etiologic factors for adenocarcinoma of the
      cervix.

PMID- 8734836
TI  - Effects of ethanol feeding and malnutrition on collagen synthesizing and
      degrading enzymes in rat pancreas.
AB  - This study was performed to delineate the combined effects of a low-fat diet and
      chronic ethanol ingestion on collagen metabolism in rat pancreas. Rats fed a very
      low-fat diet (5% of total calories as lipid) for 12 weeks developed malnutrition
      as judged by weight loss (-33% of the initial body weight) and low serum albumin
      and amylase levels. The pancreas of malnourished rats showed increased
      collagenase activity with respect to animals fed a 35% lipid diet (p < 0.05).
      Hydroxyproline content was higher in the pancreas of malnourished rats and
      collagenase activity correlated well with hydroxyproline content (r = 0.57, p =
      0.0013). Ethanol feeding for 12 weeks, regardless of the nutritional state of the
      rats, did not change the synthesis and degradation rates of collagen in the
      pancreas. The present study suggests that malnutrition may have profound effects
      on collagen metabolism.

PMID- 8734837
TI  - Adrenalectomy prevents the development of alcohol preference in male rats.
AB  - By forcing adrenalectomized (ADX) and sham-operated (SHAM) rats to chronically
      drink ethanol by mean of presentation of only one drinking bottle containing 10%
      ethanol, no differences occurred between both groups. ADX and SHAM rats were then
      exposed to chronic alcoholization using an inhalation procedure. After sejourning
      3 weeks into the alcoholization chamber, rats were submitted to a free-choice
      paradigm [water vs. a 10% (v/v) ethanol solution]. The sham-operated rats
      presented an alcohol-induced behavioral preference towards alcohol whereas
      adrenalectomized animals never exhibited a preference to ethanol. In the
      adrenalectomized rats treatment with hydrocortisone (30 micrograms/ml) given
      orally during the pulmonary alcoholization failed to modify this preference
      whereas treatment with corticosterone (25 micrograms/ml) given orally abolished
      the difference with SHAM animals. These data showed that adrenalectomy prevented
      the development of ethanol preference and the clear involvement of the
      hypothalamo-pituitary-axis in alcohol preference.

PMID- 8734838
TI  - Piracetam promotes mossy fiber synaptic reorganization in rats withdrawn from
      alcohol.
AB  - Prolonged alcohol intake affects the morphology of the hippocampal formation of
      the rat and the resulting alterations do not reverse after withdrawal. Actually,
      an increase of the degenerative activity might occur in this condition. This
      unexpected observation prompted us to test the efficacy of neuronoprotective
      drugs during withdrawal. Because in a previous study we found that piracetam, a
      cyclic derivative of GABA, once added during withdrawal impedes hippocampal cell
      loss, we decided to evaluate the effect of this compound at the synaptic level.
      Using unbiased stereological techniques, we estimated the total number of
      contacts between mossy fibers and CA3 pyramids, as well as the volume and the
      surface area of the respective pre- and postsynaptic compartments. We found that
      in piracetam-treated withdrawn rats the number of synapses was higher than that
      observed in nonpiracetam-treated and alcohol-fed animals. The mechanisms leading
      to the synaptic reorganization took place at the mossy fiber level. The
      postsynaptic compartment does not seem to participate in the reorganization. It
      is suggested that the role of piracetam in this process might depend on the
      protective effect that this compound has upon glutamatergic receptors.

PMID- 8734839
TI  - Ethanol increases uterine blood flow and fetal arterial blood oxygen tension in
      the near-term pregnant ewe.
AB  - Fetal hypoxia is a hypothesized mechanism of ethanol teratogenesis. The objective
      of this study was to test this hypothesis by determining the effects of maternal
      ethanol infusion on uterine blood flow (UBF) and fetal oxygen status. UBF was
      measured with an electromagnetic flow probe placed around the left maternal
      uterine artery of the surgically recovered instrumented near-term pregnant sheep
      at 124 +/- 3 days of gestation (term = 147 days). Experimental treatment involved
      maternal infusion of 2 g (n = 3) or 4 g (n = 5) ethanol/kg maternal body weight,
      or 0.9% saline (n = 4) over a 5-h period. Arterial blood samples were collected
      at regular intervals to monitor maternal ethanol concentration and fetal PO2.
      Maternal ethanol infusion produced a dose-dependent increase (p = 0.0009) in UBF.
      Ethanol infusion also increased (p = 0.03) fetal arterial PO2. Overall, these
      findings indicate that fetal hypoxia is not a mechanism of ethanol teratogenesis.

PMID- 8734840
TI  - Expression and activities of class IV alcohol dehydrogenase and class III
      aldehyde dehydrogenase in human mouth.
AB  - Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the principal
      enzymes responsible for the oxidation of ingested ethanol in humans. To study
      these two enzymes in surgical specimens of attached gingiva and tongue, we have
      examined the isozyme patterns by agarose isoelectric focusing and determined the
      enzyme activities. Class IV mu-ADH, class III chi-ADH, and class III ALDH3 were
      detected in the oral mucosa tissues. Gingival mu-ADH exhibited a pH optimum for
      ethanol oxidation at 10 and the K(m) value for ethanol (pH 7.5) was estimated to
      be 27 mM. At pH 7.5 and 30 degrees C, the ADH activities in the gingiva and
      tongue samples were determined to be 90.0 +/- 5.8 (mean +/- SE; n = 24) and 50.6
      +/- 5.1 (n = 3) nmol/min/g tissue (at 33 mM ethanol), and 138 +/- 11 and 55.1 +/-
      4.7 nmol/min/g tissue (at 500 mM ethanol), respectively. The ALDH activities at
      20 mM acetaldehyde were determined to be 169 +/- 19 and 50.3 +/- 8.1 nmol/min/g
      tissue for the gingiva and tongue, respectively. We conclude that ethanol can be
      significantly metabolized in human attached gingiva and lingual mucosa by mu-ADH.
      The result also suggests that, due to lacking activity of low K(m) ALDH2 and
      ALDH1, cytotoxic metabolite acetaldehyde may be involved in the etiology of
      alcohol-related oral injury.

PMID- 8734841
TI  - Effects of nimodipine and other calcium channel antagonists in alcohol-preferring
      AA rats.
AB  - Several lines of evidence suggest that L-type calcium (CA2+) channels play a role
      in excessive ethanol (EtOH) intake. In accordance with this, a considerable
      amount of antagonists for these ion channels has been found to suppress EtOH
      intake and preference in various animal models of alcoholism. The aim of the
      present study was to examine antialcohol effects of L-type Ca2+ channel
      antagonists in alcohol-preferring AA rats. These rats, a Wistar line selectively
      bred for a high 10% v/v EtOH preference in a free-choice situation, have thus far
      not been subjected to systematic investigations with Ca2+ channel antagonists.
      Therefore, effects on EtOH preference and intake, as well as on food and total
      fluid intake, were evaluated for the 1,4-dihydropyridine (DHP) derivatives
      nimodipine, felodipine, isradipine, nicardipine, nifedipine, and nitrendipine, as
      well as for the phenylalkylamine verapamil and the benzothiazepine diltiazem,
      utilizing a limited access, free-choice procedure. All DHPs were found to be
      highly effective in reducing both EtOH intake and preference, without affecting
      total fluid intake. Irrespective of route of application (IP or PO), the
      effective dose ranges were found to be very similar across compounds (10-30
      mg/kg). Nevertheless, because food intake was also reduced, the effects were not
      completely selective. For nimodipine, the (-)-enantiomer seemed to be more
      effective as its (+)-enantiomer, possibly reflecting stereoselectivity at central
      binding sites. Compared to the DHPs, verapamil produced a similar profile of
      activity, but diltiazem was found to be ineffective. These results confirm and
      extend previous findings with L-type Ca2+ channel antagonists obtained in other
      models of alcoholism and suggest that this class of compounds offers an
      interesting approach for the pharmacotherapy of alcoholism.

PMID- 8734842
TI  - Lack of effect of dopamine D2 blockade on ethanol intake in selected and
      unselected strains of rats.
AB  - Previous research has suggested that brain catecholamines may be involved in
      regulating ethanol intake. This study was designed to look more specifically at
      dopamine (DA) and whether DA D2 receptor blockade with the antagonist pimozide
      would alter ethanol consumption in rats. Subjects were male Maudsley Reactive and
      Wistar rats, the former previously shown to consume larger amounts of ethanol
      than the latter. Both strains were screened for ethanol intake by presentation of
      ethanol solutions (free choice with water) in increasing steps from 2% to 10%
      (v/v) on an alternate-day schedule. Following the screening period, animals were
      switched to a schedule of everyday presentation of the 10% (v/v) ethanol solution
      (free choice with water) for 10 baseline days. Animals were then divided into
      high and low drinking levels according to whether their mean baseline ethanol
      intake (g/kg) fell within +/- 0.5 SD of the mean intake of their group (Maudsley
      Reactives: mean = 2.55 g/kg, low drinkers < 1.63, high drinkers > 3.47; Wistars:
      mean = 2.17 g/kg, low drinkers < 1.53, high drinkers > 2.82). The animals were
      assigned to one of five treatment groups for 5 subsequent days where they
      received IP injections of pimozide (0.08, 0.24, or 0.48 mg/kg), tartaric acid, or
      saline. Following the treatment period, ethanol consumption was recorded for 5
      posttreatment days. No significant differences due to treatment were observed for
      either intake or preference of ethanol across treatments, drinking groups, or
      strains. The results obtained in the present study suggested that interference in
      DA neurotransmission through administration of the D2 antagonist pimozide does
      not significantly alter ethanol consumption in either MR or Wistar animals.

PMID- 8734843
TI  - Alcohol-induced changes in blood gases, glucose, and lactate in pregnant and
      nonpregnant rats.
AB  - The effects of alcohol and pregnancy on venous blood pH, gases (pO2, pCO2),
      bicarbonate (HCO-3), and glucose and lactate were examined in pregnant and
      nonpregnant female rats using anaerobic analytical methods of blood collection.
      Baseline measurements were obtained prior to treatment and then at 30 min, 1, 2,
      and 4 h after gastric intubation with 0, 2, 4, or 6 g/kg of alcohol. Alcohol
      produced a metabolic acidosis, increases in blood glucose and lactate
      concentrations, and an increase in blood oxygen concentration. Gestation days 18
      19 (0.8 gestation) of pregnancy were associated with a slight alkalosis, a
      decrease in oxygen concentration, no effect on glucose concentrations, and an
      increase in lactate concentrations compared with nonpregnancy. The only
      significant interaction between alcohol and pregnancy occurred for pO2 and O2C,
      wherein alcohol increased both of these parameters in nonpregnant animals only.
      These results indicate that the rat's pH response to acute alcohol infusion is
      unique because alcohol does not produce any significant changes in blood pH in
      other animal models. This change was similar in both pregnant and nonpregnant
      animals. Except for changes in blood oxygen content, the pregnant and nonpregnant
      female rat's response to alcohol were also similar as well.

PMID- 8734844
TI  - Angiotensin II antagonists block ethanol effects on the aerial righting reflex.
AB  - The purpose of the present study was to determine the effects of an angiotensin
      II (AII) AT1 antagonist, losartan 10, 15, and 20 mg/kg IP, and the AII AT2
      antagonist, PD 123319, 20 mg/kg IP on ethanol (EtOH) intoxication as measured by
      the aerial righting reflex in male rats. EtOH (25%), 2.0 g/kg, was administered
      by stomach tube under mild metaphane anesthesia and the aerial righting reflex
      was determined at 30-min intervals for 3.5 h. The AII antagonists were
      administered IP 2 h before the EtOH. There were six groups of 10 rats each: EtOH
      alone, 10, 15, or 20 mg/kg losartan plus ethanol, 20 mg/kg losartan plus 20 mg/kg
      PD 123319 plus EtOH, and 20 mg/kg losartan alone. Data were analyzed by a two-way
      ANOVA with repeated measures on one factor, time. Results show a clear
      intoxicating effect of ethanol on the aerial righting reflex that was blocked
      significantly by losartan in a dose-dependent way. Losartan alone had no
      observable effect. The administration of both antagonists, losartan and PD 123319
      injected IP in two different sites, completely blocked the EtOH effect on the
      aerial righting reflex. The involvement of AII in the mediation of EtOH
      intoxication effects on the aerial righting reflex supports results of our
      previous studies on the effects of EtOH on open field behavior, AII impairment of
      the retention of an inhibitory shock avoidance response, and AII inhibition of
      hippocampal granule cell long-term potentiation, all of which can be blocked by
      losartan.

PMID- 8734845
TI  - Ganglioside long-chain base composition of rat brain subcellular fractions after
      chronic ethanol administration.
AB  - Rats of two different ages (2 and 7 months) were treated with an ethanol
      containing liquid diet for 24 days and change of the ceramide composition of
      gangliosides were studied in the brain synaptosomal, microsomal and myelin
      fractions. Greater differences were observed in the younger age, where ethanol
      treatment caused a significant increase of C20:1 LCB in GM1 ganglioside of
      synaptosomes and microsomes and in GD1a of myelin.

PMID- 8734846
TI  - Effects of ethanol consumption by adolescent alcohol-preferring P rats on
      subsequent behavioral performance in the cross-maze and slip funnel tests.
AB  - Neonatal alcohol exposure during the first 1-2 weeks of age is known to produce
      subsequent behavioral hyperactivity in rats. However, little is known about the
      effects of alcohol exposure during adolescence on subsequent adult behavior. In
      the present study, male and female P rats had free access to 10% alcohol during
      adolescence (3-8 weeks of age). After 8 days of abstinence, their behavior was
      evaluated in the cross-maze and in the inescapable slip funnel tests during the
      10th week of age. Two-way ANOVAs revealed significant effects of alcohol drinking
      on several variables. Compared to alcohol-naive rats, the alcohol-exposed group
      started exploration earlier (3.5 +/- 0.3 vs. 5.4 +/- 0.7 s, p = 0.03) and made
      fewer defecations. In the slip funnel test, the alcohol group spent more time
      immobile (130 +/- 7 vs. 107 +/- 5 s, p = 0.01) and less time attempting to escape
      out of the funnel (11 +/- 2 vs. 28 +/- 5 s, p = 0.002) than the control group.
      Overall, the results suggest that the effects of alcohol drinking by P rats
      during adolescence on subsequent behavior are to reduce novelty-induced anxiety
      (cross-maze test) and lower response to stress induced by an inescapable
      situation (slip-funnel test).

PMID- 8734847
TI  - P450 2E1 expression in liver, kidney, and lung of rats treated with single or
      combined inducers.
AB  - Ethanol consumption combined with smoking increase the risk of cancer in many
      tissues. Such a mechanism implies the involvement of cytochrome P450 alcohol
      (CYP2E1), which is regulated by numerous xenobiotics. The combination of P450 2E1
      inducers (acetone or pyridine) and 3-methylcholanthrene during rat treatment was
      shown to decrease the liver P450 2E1 content while it enhanced its expression in
      kidney. It is suggested that this differential tissue response helps explain the
      organotropy of nitrosamine carcinogenicity.

PMID- 8734848
TI  - Serum lipoprotein(a) [Lp(a)] in alcoholic men: effect of withdrawal.
AB  - This study examines the effect of alcohol withdrawal on lipoprotein(a) [Lp(a)] in
      24 male, middle-aged chronic alcohol abusers admitted for withdrawal therapy.
      Serum concentration of Lp(a) was determined before and during the first 3 weeks
      of abstinence. The changes in three sialylated proteins [Lp(a), alpha 1
      antitrypsin (alpha 1-AT), and haptoglobin (Hp)] and in desialylated transferrin
      (CDT) were also determined in 14 patients. After the 3 weeks of withdrawal
      therapy, the mean and median Lp(a) concentrations increased (p = 0.0001). The
      changes in Lp(a) levels were not related to the changes in dietary intake nor to
      the decrease in total HDL, HDL3, HDL2 cholesterol, Apo A-I, and Apo B. In the
      subgroup of 14 chronic alcohol abusers, Lp(a) levels increased parallel with Hp
      and alpha 1-AT, whereas CDT decreased. It is concluded that the impact of alcohol
      on sialylated proteins may be one of the mechanisms responsible for the increase
      in plasma Lp(a) after alcohol withdrawal.

PMID- 8734849
TI  - Different levels of [3H]MK-801 binding in long-sleep and short-sleep lines of
      mice.
AB  - The long-sleep (LS) and short-sleep (SS) lines of mice were selectively bred for
      differential sensitivity to the hypnotic effects of ethanol. Several studies
      suggest that excitatory amino acid receptor systems are involved in these
      genetically determined differences in sensitivity to ethanol. The experiments
      described in this article examine further the potential role of NMDA excitatory
      amino acid receptors in genetically determined differences in hypnotic
      sensitivity to ethanol by measuring [3H]MK-801 binding in eight brain regions of
      LS and SS lines of mice. Significantly greater levels of binding were found in SS
      hippocampus and striatum. Binding levels in the remaining brain regions revealed
      no significant between-line differences. Affinity differences between regions
      were seen but no between-line differences in affinity were found in any brain
      region. These findings lend support to the hypothesis that differences in NMDA
      receptor systems are part of the genetically determined biochemistry that
      produces differential hypnotic sensitivity to ethanol in LS and SS mice.

PMID- 8734850
TI  - [Hepatic hemangioma--an increasing diagnostic problem in clinical practice].

PMID- 8734851
TI  - [Hepatic hemangioma. Analysis of 103 cases. Clinical considerations and imaging
      methods].
AB  - Hemangiomas are the most common benign vascular tumor found in the liver. In this
      study, 103 cases of hepatic hemangiomas were analysed in a retrospective manner.
      Image aspects such as those seen in ultrassonography, computed tomography,
      nuclear magnetic resonance and arteriography are discussed. The incidence was
      higher amongst the female sex, between individuals from 40 to 60 years old, which
      presented predominantly without symptoms (66%) and localized mainly in the right
      hepatic lobe (74%). The meaning of those aspects, when adopted, permits the
      clinicians to differentiate benign from malignant nodular lesions in the liver.

PMID- 8734852
TI  - [Prevalence of hepatitis C virus in urban and rural populations of northeast
      Brazil-pilot study].
AB  - Hepatitis C virus can be found in all continents. However, differences exist with
      respect to its prevalence. In Brazil, epidemiological data are scarce, and are
      based, in their majority, on information obtained from blood donors and not from
      the general population. Our objective is to show the prevalence of anti-HCV in
      two distinct populations: one rural and one urban: Salvador, a metropolis, and
      Castro Alves, a rural village with very little contact with other populations.
      Eight hundred individuals from Salvador and 800 from Castro Alves were randomly
      visited. After obtaining consent, we collected blood samples for serology tests
      and determination of ALT levels. The anti-HCV antibody was tested using ELISA II
      (ABBOTT Labs), and confirmed by RIBA III (Chiron). We studied the prevalence of
      anti-HCV in two populations and its distribution with respect to age group and
      sex and ALT level. chi 2 and Fisher exact were used for the statistical analysis.
      Of the 800 individuals from Salvador, 44% were women and 56% were men. The age
      group varied from 10 to 70 years, with an average age of 42. Ten (1.25%)
      individuals were anti-HCV positive in the urban population and none in the rural
      population (P < 0.001). No evident correlation was found regarding sex and ALT
      level, between anti-HCV positive and anti-HCV negative individuals in the urban
      population. In conclusion, our results suggest a higher prevalence of HCV
      infection in the urban population probably due to a high level of exposure. The
      sero-epidemiological studies using blood donors do not reflect the
      epidemiological reality of HCV in Brazil due to selection bias which could
      overestimate its seroprevelence.

PMID- 8734853
TI  - [Reactivation of ulcerative rectocolitis with the use of non-steroidal anti
      inflammatory drugs. Report of a case and review of the literature].
AB  - The case of a patient with ulcerative colitis and isolated sacro-ileitis is
      presented. She suffered reactivation of the intestinal disease with diclofenac.
      The patient was allergic to sulfasalazine and was using fish oil fatty acid. The
      possible mechanisms of reactivation of the inflammatory bowel disease with non
      steroidal anti-inflammatory drugs are discussed. It is suggested when necessary
      the utilization of non-steroidal anti-inflammatory drugs that inhibits the
      lipoxygenase in these patients.

PMID- 8734854
TI  - [Current approach to pancreatic necrosis].
AB  - The incidence of acute pancreatitis is increasing. Necrosis occurs in 10 to 20%
      of the cases, and is associated with great morbidity and mortality. The diagnosis
      of pancreatic necrosis can be suspected clinically and biochemically, and
      confirmed with imaging methods. A computerized tomography with contrast injection
      (dynamic pancreatography) is the best diagnostic method. Treatment of pancreatic
      necrosis is primarily conservative. Prophylactic antibiotic therapy is reserved
      for the biliary pancreatitis and for severe cases. When pancreatic infection is
      suspected, computerized tomography or ultrasonic exam guided percutaneous
      aspirative punction must be performed, with Gram stain and culture of the
      material aspirated. If bacterial infection is present, adequate antibiotic
      therapy with good penetration in necrotic tissue must be provided associated with
      surgical necrosectomy and local washing or open drainage.

PMID- 8734855
TI  - [Liver abscess in childhood: report of 8 cases].
AB  - The authors present eight cases of children with liver abscess diagnosed in the
      Pediatric Nursery of the "Hospital das Clinicas", State University of Campinas,
      SP, Brazil, during eight years. Five children were younger than five years. They
      were four boys and four girls. The symptomatology was inespecific. Staphylococcus
      aureus was the more frequent etiologic agent and in two cases it was seen Ascaris
      lumbricoides worm inside the abscess. The findings of ultrasound and
      computadorized tomography were similar. In most cases, were employed the
      association of broad spectrum antibiotics and percutaneous draining, and a good
      clinical outcome was observed in all patients.

PMID- 8734856
TI  - [Hydrogen test (H2) in the air expired for the diagnosis of small bowel bacterial
      overgrowth].
AB  - The small bowel bacterial overgrowth is characterized by the presence of colonic
      flora in the small bowel, may to lead malabsorption and/or diarrhea and/or weight
      loss. The small-bowel culture has served as the "gold standard" for diagnosing
      bacterial overgrowth. The colonic flora is able to ferment carbohydrates that are
      present in the lumen of the intestinal tract with production of hydrogen, which
      is subsequently observed and excreted by the breath. Therefore, the hydrogen
      breath test after oral carbohydrates administration represents an alternative,
      non-invasive and specific method for diagnosing small bowel bacterial overgrowth.

PMID- 8734857
TI  - Microcystin hepatitis.

PMID- 8734858
TI  - [Remodel, remodelment, remodelling].

PMID- 8734859
TI  - [Comparative study between verapamil and adenosine triphosphate in the treatment
      of paroxysmal supraventricular tachycardia].
AB  - PURPOSE: To evaluate the efficacy and safety of intravenous (IV) adenosine
      triphosphate (ATP) and verapamil to convert acute episodes of paroxysmal
      supraventricular tachycardia (PSVT) to sinus rhythm. METHODS: Fifty patients with
      PSVT were randomized in two groups: A) 25 treated with IV bolus of ATP (10 or
      20mg), and V) 25 treated with IV verapamil, up to 15mg, during 3min. We evaluated
      the time delay necessary to convert the arrhytmia, doses, and side-effects.
      Patients with acute ischemic syndromes (< 3 weeks), severe congestive heart
      failure, and treatment with dipyridamole or methylxanthine were excluded.
      RESULTS: There were no differences between the two groups regarding to age, sex,
      and success rate. The average time till reversal were respectively, 30s and 248s
      for ATP and verapamil. Ventricular ectopy and general discomfort were observed in
      33% of patients receiving ATP, whereas no side-effects occurred in group V.
      CONCLUSION: ATP is a good option to convert rapidly PSVT to sinus rhythm and,
      probably, could be the first choice to treat PSVT patients with ventricular
      dysfunction.

PMID- 8734860
TI  - [Diabetes mellitus and ischemie heart disease. Comparison by gender].
AB  - PURPOSE: To test the association between diabetes mellitus and ischaemic heart
      disease (IHD) in males and females, after adjusting for known confounders and/or
      modifiers of effect. METHODS: The study was designed as a case-control and the
      period of data collection was one year (March/93 until February/94). The
      association between diabetes mellitus and IHD was evaluated in each one of two
      groups: one composed by men the other by women, aged 30-69 years living in the
      city of Sao Paulo. The respective samples sizes were 547 and 286. Logistic
      regression was the statistical method used to do the analysis of the data.
      RESULTS: There were similar odds ratios in both genders and diabetes was not
      considered an independent risk factor for IHD. In each one of the groups the
      variables hypertension, hypercholesterolemia, smoking and familial history were
      considered independent risk factors to IHD. The interaction between diabetes and
      exposures levels of other variables was not statistically significant.
      CONCLUSION: The presence of major risk factors in the models contributed to the
      disappearance of the association between diabetes mellitus and IHD.

PMID- 8734861
TI  - [Fungal infections in 100 patients subjected to heart transplantation].
AB  - PURPOSE: To evaluate prevalence, causes, clinical aspects, topography and deaths
      due to fungal infections diagnosed in a series of patients submitted to heart
      transplantation. METHODS: 100 consecutive patients submitted to heart
      transplantation were studied. Follow-up was three to 90 (mean 25.38 +/- 25.97)
      months. Fungal infections were diagnosed by the Centers for Disease Control
      criteria. RESULTS: Forty seven fungal infections were found, with three deaths
      caused mainly by fungal infection. The most common infection in this series was
      oral infection by Candida albicans, Acremonium sp, Aspergillus sp, Candida
      tropicalis, Histoplasma capsulatum and Pneumocystis carinii were also responsible
      for infections in this patient population. CONCLUSION: Fungal infections caused
      three deaths in this series, and were responsible for increased morbidity. The
      authors suggest prophylactic and therapeutic recommendations.

PMID- 8734862
TI  - [Surgical myocardial revascularization in young patients].
AB  - PURPOSE: To determine early and late results of surgical myocardial
      revascularization (SMR) in young patients. METHODS: We studied retrospectively 73
      patients aging less than 40 years and submitted to SMR between 1975 and 1989. The
      method used was patient card review and thelephone contact with the patient or
      his physician. RESULTS: Follow-up was obtained in all cases in a period of 2 to
      185 (59.9 +/- 41.0) months. Of the coronary risk factors smoking was the most
      frequent. One vessel coronary artery disease was observed in 16 (21.9%) patients,
      2 and 3 vessel coronary artery disease in 26 (35.6%) and 32 (43.8%) patients
      respectively. SMR was considered complete in 68 (93.2%) patients. An associated
      procedure was performed on 10 cases: Left ventricular aneurysm repair in 9
      (12.3%) and mitral valve replacement in one (1.4%). Perioperative myocardial
      infarction occurred in 7 (9.5%) patients and one of them died (operative
      mortality: 1.4%). During follow-up, 6 (8.3%) patients died with an actuarial
      survival rate of 89.1% at 15 years. An event free survival rate of 68.3% was
      observed at 10 years. From 66 survivors, 53 (80.3%) were asymptomatic at late
      follow-up and 48 (72.7%) patients returned to work. CONCLUSION: Surgical
      myocardial revascularization in young patients associated with medical treatment,
      has good early and late results with a high percentage of patients asymptomatic
      and reemployed at a late follow-up.

PMID- 8734863
TI  - [High risk percutaneous transluminal coronary angioplasty after mechanical
      recanalization of the unprotected left main stem coronary artery and during
      myocardial infarction].
AB  - A 70 years-old man, with acute myocardial infarction, was submitted to
      successfull percutaneous transluminal coronary angioplasty of the left main stem
      coronary artery, following recanalization of that artery.

PMID- 8734864
TI  - [Chagas disease perspectives for the 21st century].

PMID- 8734865
TI  - [Fetal heart rhythm disorders. Detection and prenatal management].

PMID- 8734866
TI  - [The use of adenosine triphosphate in supraventricular paroxysmal tachycardia].

PMID- 8734867
TI  - -Apical hyperthophic cardiomyopathy--.

PMID- 8734868
TI  - [Clinical, electrical and surgical treatment of hypertrophic cardiomyopathy].

PMID- 8734869
TI  - [Hypertrophic cardiomyopathy: concepts and classification].

PMID- 8734870
TI  - [Hypertrophic cardiomyopathy in special conditions-child, adolescent and aged].

PMID- 8734871
TI  - [Hypertrophic cardiomyopathy. Clinical characteristics, diagnostic methods and
      natural history].

PMID- 8734872
TI  - The effect of partial meniscectomy on the long-term prognosis of knees with
      localized, severe chondral damage. A twelve- to fifteen-year followup.
AB  - We retrospectively matched 42 patients with unilateral chondral damage in the
      weightbearing zone of one knee compartment according to sex, age, location of
      chondral damage, and follow-up time. Two groups of 21 patients were formed. One
      group had chondral damage only. The other group had chondral damage and a
      meniscal tear treated with partial meniscectomy. After 12 to 15 years, all
      patients were reexamined. Twenty-nine percent (N = 6) of the patients who had a
      partial meniscectomy needed repeat meniscal surgery during followup. No patients
      with isolated chondral damage developed meniscal symptoms, and only three
      patients underwent minor surgeries (P < 0.02). At the follow-up evaluation, both
      groups had similar knee function with a mean Lysholm score of 87 points. However,
      most patients had reduced their sports activities from competitive individual
      sports before injury to noncompetitive physical fitness exercise at followup. At
      the roentgenologic examination, patients who had partial meniscectomies had more
      severe roentgenologic signs of osteoarthritis than patients who had chondral
      damage only (P < 0.03). Meniscectomy, varus knee alignment at the follow-up
      evaluation (P < 0.04), and age older than 30 years (P < 0.04) at the time of the
      operation were associated with a higher incidence of osteoarthritis.

PMID- 8734873
TI  - Rotator cuff injury in contact athletes.
AB  - The causes and incidence of rotator cuff injuries in patients under the age of 40
      has not been clearly established. The present study focuses on a group of 10 male
      contact athletes with rotator cuff injuries related to trauma sustained during
      football (ages from 24 to 36 years). Symptoms included pain and dysfunction in
      all 10 patients and a positive shrug sign in 8 of 10. The diagnoses for these
      patients were two isolated contusions, five partial-thickness tears, and three
      full-thickness tears. Surgery was performed on all patients after nonoperative
      treatment failed. Three partial-thickness tears were arthroscopically debrided.
      One full-thickness and two partial-thickness tears were repaired using the
      arthroscopically assisted miniarthrotomy technique. An open repair was performed
      in two patients. Two isolated rotator cuff contusions were arthroscopically
      debrided. The average followup was 21 months. Nine of 10 athletes returned to
      active participation in football, 7 of these at their preinjury levels. The
      diagnosis of rotator cuff injury should be considered in a contact athlete who
      has persistent shoulder pain, impingement signs, weakness, and a positive shrug
      sign. Arthroscopic debridement of the subacromial space followed by debridement
      or repair of rotator cuff tears, as clinically indicated, resulted in a marked
      improvement in function and rapid return to sport for these patients.

PMID- 8734874
TI  - Arthroscopic anterior labral reconstruction using a transglenoid suture
      technique. Results in active-duty military patients.
AB  - We report the clinical outcome of arthroscopic labral reconstruction using a
      transglenoid suture technique in a young, active-duty military population. Forty
      eight patients (49 shoulders) with varying degrees of glenohumeral instability
      underwent arthroscopic labral reconstruction using a transglenoid suture
      technique. All patients had traumatic injuries to their shoulders and all
      patients had magnetic resonance imaging scans demonstrating anterior labral
      tears. Postoperatively, the patients' shoulders were immobilized for up to 6
      weeks. At a mean followup of 30 months (range, 12 to 49), 17 of the 41 patients
      (41%) with preoperative dislocation or subluxation had recurrent instability.
      Nine of these patients subsequently underwent open reconstruction procedures for
      recurrent instability. On the basis of the Rowe rating system, 53% had excellent
      or good results and 47% had fair or poor results. The overall perioperative
      complication rate was 14%. Suprascapular nerve palsy occurred in three cases
      (6%). Using the Fisher exact test, we determined that immobilization for 6 weeks
      postoperatively correlated with a lower recurrence rate in the patients with a
      history of glenohumeral dislocation (P = 0.007). The results of arthroscopic
      labral reconstruction using transglenoid sutures in the military patient are
      inferior to the reported 3% to 5% recurrence rate with open Bankart procedures,
      and the transglenoid pin technique jeopardizes the suprascapular nerve.

PMID- 8734875
TI  - Posterior instability of the glenohumeral joint. A technique of repair.
AB  - Seventeen patients underwent posterior capsulotendinous tensioning procedures to
      eliminate recurrent posterior glenohumeral instability. Fourteen patients were
      evaluated an average of 44 months (range, 18 to 98) after surgery. The average
      patient age was 27 years. Before surgery, all patients were unable to perform
      their activities of daily living, occupational activities, and athletic
      activities. Preoperatively, the average pain rating score on a visual analog
      scale was 5 of 10 at rest and 9 of 10 with activities. Six patients had previous
      anterior reconstructions. After surgery, the average range of motion was 174
      degrees of forward elevation and 69 degrees of external rotation; internal
      rotation was to the thumb level of T-8. No patient had a recurrence of posterior
      instability. After surgery, the average pain rating score was 2 of 10 at rest and
      4 of 10 with activities. All patients improved after their operations, but four
      patients were minimally disabled from activities of daily living; six patients
      experienced shoulder fatigue at work; and four patients had difficulty with
      sports activities. Overall, 13 of the 14 patients were satisfied with their
      surgical procedures and their outcomes.

PMID- 8734876
TI  - Shoulder range of motion in elite tennis players. Effect of age and years of
      tournament play.
AB  - We studied glenohumeral rotational range of motion in 39 members of the United
      States Tennis Association National Tennis Team and touring professional program.
      We took goniometric measurements of internal and external rotation of dominant
      and nondominant shoulders at the glenohumeral joint with the humerus at 90
      degrees of abduction. We categorized the tennis players by age and by years of
      tournament play. Results were analyzed by total rotation, internal rotation,
      external rotation, and dominant-to-nondominant shoulder differences. In our
      results, dominant internal rotation of the shoulder declined and the difference
      between dominant and nondominant internal rotation increased with both age and
      years of tournament play. Men and women tennis players showed the same degree of
      deficits in range of motion. Significant analysis of variance statistics were
      calculated for dominant internal rotation with years of total play, dominant
      total rotation with years of total play, and nondominant total rotation with age.
      Moderate negative correlations were found between dominant internal rotation and
      years of total play and dominant total rotation and years of total play. These
      results indicate a loss of internal rotation that seems progressive with longer
      periods of play. This loss of internal rotation of the shoulder is an absolute
      loss of motion because total rotation also decreases. Early detection and a
      corrective training program should be considered because adaptations may result
      in deleterious biomechanics affecting both performance and risk of injury.

PMID- 8734877
TI  - A biomechanical analysis of rotator cuff deficiency in a cadaveric model.
AB  - We conducted this cadaveric study to define a biomechanical rationale for rotator
      cuff function in several deficiency states. A dynamic shoulder testing apparatus
      was used to examine change in middle deltoid muscle force and humeral translation
      associated with simulated rotator cuff tendon paralyses and various sizes of
      rotator cuff tears. Supraspinatus paralysis resulted in a significant increase
      (101%) in the middle deltoid force required to initiate abduction. This increase
      diminished to only 12% for full glenohumeral abduction. The glenohumeral joint
      maintained ball-and-socket kinematics during glenohumeral abduction in the
      scapular plane with an intact rotator cuff. No significant alterations in humeral
      translation occurred with a simulated supraspinatus paralysis, nor with 1-, 3-,
      and 5-cm rotator cuff tears, provided the infraspinatus tendon was functional.
      Global tears resulted in an inability to elevate beyond 25 degrees of
      glenohumeral abduction despite a threefold increase in middle deltoid force.
      These results validated the importance of the supraspinatus tendon during the
      initiation of abduction. Glenohumeral joint motion was not affected when the
      "transverse force couple" (subscapularis, infraspinatus, and teres minor tendons)
      remained intact. Significant changes in glenohumeral joint motion occurred only
      if paralysis or anatomic deficiency violated this force couple. Finally, this
      model confirmed that rotator cuff disease treatment must address function in
      addition to anatomy.

PMID- 8734878
TI  - The role of the acromioclavicular ligaments and the effect of distal clavicle
      resection.
AB  - To determine the role of the acromioclavicular ligaments in controlling scapular
      rotation about the distal clavicle and the effects of distal clavicle resection,
      we used 13 fresh shoulders consisting of the clavicle, acromioclavicular
      ligaments, coracoclavicular ligaments, and scapula. The range of motion was
      measured using a specially designed goniometer for each of the three orthogonal
      axes of rotation of the scapula with reference to the clavicle: anterior
      posterior axial rotation, protraction-retraction, and abduction-adduction. We did
      two experiments involving sequential sectioning. Range of motion was measured in
      the intact shoulder and after each sectioning cut. The order of sectioning in
      Experiment 1 (six shoulders) was 1) the inferior acromioclavicular ligament, 2)
      removal of 5 mm of the distal clavicle, and 3) the superior acromioclavicular
      ligament. In Experiment 2 (seven shoulders) the order was 1) the superior
      acromioclavicular ligament, 2) removal of 5 mm of the distal clavicle, and 3) the
      inferior acromioclavicular ligament. The most important results were 1) only 5 mm
      of the distal clavicle needs to be resected to ensure that no bone-to-bone
      contact occurs in rotation postoperatively and 2) there was no difference in the
      end result (for range of motion in any of the three axes) whether the inferior
      acromioclavicular ligament or the superior acromioclavicular ligament was cut
      before removal of 5 mm of the distal clavicle.

PMID- 8734879
TI  - Primary repair for posterior cruciate ligament injuries. An eight-year followup
      of fifty-three patients.
AB  - We reviewed 53 of 58 patients who had primary repairs of posterior cruciate
      ligament injuries between 1981 and 1988. Sixteen patients had isolated posterior
      cruciate ligament ruptures, 16 had complex injuries with capsular and collateral
      ligament involvement, and 21 had additional anterior cruciate ligament ruptures.
      Forty-six patients were treated by transosseous multiple-loop sutures and seven
      with bony avulsions by screw osteosynthesis. The mean follow-up time was 7.5
      years (range, 3 to 12). All patients were examined subjectively (questionnaire)
      and objectively (clinical examination, KT-1000 arthrometer, functional testing,
      radiographs, and Cybex II isokinetic strength analysis). The results were graded
      according to the International Knee Documentation Committee evaluation form and
      the Lysholm score. The average Lysholm score was 82.4 (range, 40 to 100). Thirty
      eight patients returned to their preinjury activities at the same intensity
      level. The patients' subjective assessments were normal or nearly normal in 35
      patients. The posterior drawer test was negative or 1+ in 46 patients. Cybex
      isokinetic strength analysis revealed a decrease in quadriceps muscle strength of
      the involved limb by 10.5% (P < 0.01). Our data suggest that primary repair of
      posterior cruciate ligament ruptures provides good results after 8 years in
      approximately two thirds of the patients. Distal ligamentous ruptures, lack of
      athletic activity, and temporary olecranization correlated with poor results.
      Bony avulsions, midsubstance or proximal ruptures, and athletic activity
      correlated with good results.

PMID- 8734880
TI  - Long-term followup of the untreated isolated posterior cruciate ligament
      deficient knee.
AB  - We evaluated 38 subjects with isolated posterior cruciate ligament-deficient
      knees at a mean of 13.4 years (range, 5 to 38) after injury to study the
      occurrence of symptoms, disabilities, and articular degeneration. Each subject
      completed a standardized questionnaire, physical examination, and had radiographs
      taken of both knees. Eight (21%) patients had surgeries for meniscal injuries
      after their posterior cruciate ligament injuries. The mean questionnaire score
      for function (50-point maximum) was 34.4 +/- 6.5 (SD) for the patients who did
      have meniscal surgeries versus 40.0 +/- 8.7 for the 30 patients who did not (P =
      0.05). Among the 30 patients with isolated posterior cruciate ligament-deficient
      knees with normal menisci, 24 (81%) had at least occasional pain and 17 (56%) had
      at least occasional swelling. As time from injury increased, increased articular
      degeneration on radiographs was seen (P = 0.037). Our study suggests that the
      prognosis for the isolated posterior cruciate ligament-deficient knee varies.
      Some patients experience significant symptoms and articular deterioration, while
      others are essentially asymptomatic and maintain their usual knee function.

PMID- 8734881
TI  - The popliteofibular ligament. Rediscovery of a key element in posterolateral
      stability.
AB  - We have recently become aware of a strong direct attachment of the popliteal
      tendon to the fibula. To investigate the importance of this attachment, we
      examined 20 cadaveric knees. The popliteofibular ligament was identified in all
      20 knees. The cross-sectional area of the popliteofibular ligament was 6.9 +/-
      2.1 mm2, compared with 7.2 +/- 2.7 mm2 for the lateral collateral ligament.
      Biomechanical testing of these structures, simulating a purely varus stress on
      the knee, revealed that the lateral collateral ligament always failed first,
      followed by the popliteofibular ligament, and then the muscle belly of the
      popliteus. The mean maximal force to failure of the popliteofibular ligament
      approached 425 N (range, 204 to 778), compared with 750 N (range, 317 to 1203)
      for the lateral collateral ligament. Our results indicate that the
      popliteofibular ligament contributes to posterolateral stability.

PMID- 8734882
TI  - Injuries in indoor soccer. The Lake Placid Dawn to Dark Soccer Tournament.
AB  - We conducted a prospective study of soccer injuries during the Soccer America
      Dawn to Dark Indoor Soccer Tournament, which was organized by the Lake Placid
      Soccer Center, Lake Placid, New York, 1993. Eight hundred twenty-four players
      competed in open men's, open women's, over-30 men's, and mixed divisions. The
      overall rate of injury per 100 player hours was 4.44, with a rate of 5.79 in the
      open men's, 4.74 in the open women's, 2.73 in the over-30 men's, and 1.54 for the
      mixed divisions. The differences in injury rates for men versus women and men
      versus older men were not statistically significant. Twenty-five of the 38
      injuries (65.8%) were mild, with 27 injuries (71.4%) occurring in the lower
      extremities. Ankle sprains were the most common injuries and combined ligamentous
      injuries to the knee were the most common severe injuries. As the injuries
      increased in severity, they were more likely to be noncontact injuries. The data
      demonstrate the low incidence of injury in male and female indoor soccer
      participants. The data also show the similarity in the types of injuries
      sustained by indoor and outdoor soccer players.

PMID- 8734883
TI  - Sports injuries in the game of hurling. A one-year prospective study.
AB  - A prospective study of hurling injuries was conducted over the 8 months of one
      season on 74 players. These athletes averaged 4.30 +/- 2.58 hours per week of
      training and 1.15 +/- 0.21 hours per week of matches. Mean time of injury was
      1.20 +/- 2.53 days in the hospital, 20.34 +/- 19.25 days off sport, and 13.34 +/-
      17.25 days of restricted activity. Together this injury time amounts to 14.3% of
      the season. There were 92 match- and 43 training-related injuries, giving 342.47
      injuries per 10,000 hours of matches and 43.83 injuries per 10,000 hours of
      training. Overall, there were 369.9 days of injury per 1000 hours of
      participation. The most common type of injury was muscle strain (24.4% of the 135
      total injuries). The hamstrings was the most common site of strain, accounting
      for 41% of these injuries. Contusions comprised 16.3% of the injuries and sprains
      comprised 15.6%. The most frequently injured sites were the finger (13%),
      hamstrings (12%), back (11%), head (9%), and knee and ankle (9%). Forty-one
      percent of the injuries were attributed to foul play. The results of the study
      suggest that the incidence of injuries in hurling is high and may be attributed
      to poor conditioning, poor protection, and lack of enforcement of the rules.

PMID- 8734884
TI  - Comparison of failure strength between metallic and absorbable interference
      screws. Influence of insertion torque, tunnel-bone block gap, bone mineral
      density, and interference.
AB  - Because of the good initial fixation strength of interference screws used in
      anterior cruciate ligament reconstruction, metal interference screws have become
      the standard method for fixation of bone-patellar tendon-bone grafts. To avoid
      some of the complications with metal screws, a bioabsorbable interference screw
      was developed. Data on fixation strength in older human cadavers indicate a
      similar failure strength between bioabsorbable and metal screws. We studied the
      failure mechanisms, insertion torques, and fixation strengths of absorbable and
      metal interference screws in cadaveric knees from young and middle-aged donors.
      With identical gap and screw size, the mean insertion torque for the metal screws
      (mean, 1.5 N-m; SD, 0.8) was significantly higher than for the absorbable screws
      (mean, 0.3 N-m; SD, 0.19). The mean failure load for the metal screws (mean 640
      N; SD, 201) was also significantly higher than for the absorbable screws (mean,
      418 N; SD, 118).

PMID- 8734885
TI  - The relationship between tunnel placement and clinical results after anterior
      cruciate ligament reconstruction.
AB  - To correlate clinical results after anterior cruciate ligament reconstruction
      with tunnel placement measured radiographically, we prospectively studied 128
      patients who had arthroscopically assisted bone-patellar tendon-bone
      reconstructions. Patients with bilateral anterior cruciate ligament
      reconstructions, other significant knee ligament injuries, or those undergoing
      chondroplasty or meniscal repairs were excluded, leaving 42 patients. The
      relationship between radiographic tunnel position and clinical results was
      determined using the Lysholm score, KT-1000 arthrometer testing, the Tegner
      activity level, and the pivot shift and Lachman tests. Clinical results
      correlated positively with posterior femoral tunnel placement on lateral
      radiographs and negatively with excessive anterior tibial tunnel placement.
      Specifically, when femoral tunnels were placed at least 60% posterior along
      Blumensaat's line and tibial tunnels were at least 20% posterior along the tibial
      plateau, 69% of patients had good or excellent Lysholm scores and 79% had KT-1000
      arthrometer maximum manual side-to-side differences of 3 mm or less. When the
      above criteria were not met, 50% of patients had good or excellent Lysholm scores
      and 22% had KT-1000 arthrometer maximum manual side-to-side differences of 3 mm
      or less. This close correlation indicates that satisfactory radiographic tunnel
      position influences outcome after anterior cruciate ligament reconstruction.

PMID- 8734886
TI  - Strategies for attachment site locations and twist of the intraarticular anterior
      cruciate ligament graft.
AB  - We modeled an intraarticular anterior cruciate ligament graft and investigated
      the effects of attachment orientation and twist of the graft on its isometry
      during quadriceps muscle loading. Physiologic levels of quadriceps muscle loads
      were applied to 15 intact cadaveric knees. We measured the changes in distance
      between points on the tibia and femur for knee flexion angles between 0 degree
      and 120 degrees using a three-dimensional digitizer. Selected points on the tibia
      and femur, representing graft attachment sites, allowed us to model the graft as
      a broad band. Distance was used to approximate graft fiber length. A 180 degrees
      twist in the graft significantly reduced the maximal range of changes in distance
      when the graft was attached in the anteroposterior direction. Range is defined as
      the difference between the largest and smallest changes in distance among the
      fibers of the graft for a given angle of flexion. This reduction enhanced
      isometry among the fibers of the graft. Enhanced isometry would be expected to
      enhance load sharing among these fibers, thereby increasing the overall strength
      of the graft. For a graft 10 mm wide and 4 mm thick, the dimensions of a typical
      patellar tendon graft, the best overall isometry was found when the breadth of
      the graft was attached to the tibia in the mediolateral direction, to the femur
      along the most isometric line, and with a 180 degrees twist in the graft.

PMID- 8734887
TI  - Achieving full range of motion after anterior cruciate ligament reconstruction.
AB  - A review of 119 consecutive anterior cruciate ligament reconstructions showed
      that the time from injury to surgery (early versus delayed) did not make a
      difference in obtaining full range of motion. Only patients with late surgery had
      a slight decrease in range of motion. Followup data were obtained for 111
      reconstructions. Twenty-one were early surgeries (1 to 14 days), 22 were delayed
      surgeries (15 to 28 days), and 68 were late surgeries (more than 28 days). The
      patients involved in the 21 early surgeries obtained 0 degree of knee extension
      or better and 135 degrees of knee flexion or better. The patients involved in the
      22 delayed reconstructions reached 0 degree of knee extension or better and 135
      degrees of flexion or better. Among the patients with the 68 late surgeries, 93%
      of the knees reached 0 degree of extension or better and all reached at least 135
      degrees of flexion. The five patients who did not achieve full knee extension had
      extension loses less than 4 degrees. All 111 reconstructions were determined
      stable when full range of motion was achieved based on clinical examination,
      which included the Lachman test, anterior drawer test, pivot shift, and KT-1000
      arthrometer when appropriate.

PMID- 8734888
TI  - Stability of the braced ankle. A biomechanical investigation.
AB  - We measured the bare ankle and the braced angle-torque relationships in 12
      uninjured volunteers under static and dynamic conditions within the full range of
      inversion motion. These relationships were measured with a specially designed
      mechanical device that allowed inversion movements with angular velocities up to
      850 deg/sec. In testing the bare ankle under static conditions, the torque showed
      a 10-fold increase within the full range of motion (average, from 0.9 N-m at 7
      degrees to about 8 N-m at 48 degrees of inversion). The slope of the angle-torque
      relationship increased under dynamic conditions giving higher torque values (up
      to 18 N-m on average). Both orthoses induced similar additional torques that
      increased linearly, up to about 6 N-m at 45 degrees, with higher angles of
      inversion. These additional torques are small compared with the amount of stress
      applied to the foot during a typical ankle sprain situation, such as recovering
      from a jump. Therefore, we propose that orthotic devices increase the ankle
      torque, counteracting the inversion movement, and also prevent the start of the
      inversion movement by preloading and maintaining the ankle in a proper anatomic
      position with optimal contact between the articular surfaces.

PMID- 8734889
TI  - Electromyographic latency changes in the ankle musculature during inversion
      moments.
AB  - Ten uninjured subjects (ages 18 to 30 years) had electromyographic testing of the
      peroneus longus, peroneus brevis, and tibialis anterior muscles in response to
      inversion moments at two speeds (50 and 200 deg/sec) and two joint angles
      (neutral and 20 degrees of plantar flexion) using a hydraulically controlled tilt
      platform. Subjects underwent 10 trials of each type of inversion moment on Day 1
      testing, which included both legs. On Day 2, subjects again underwent 10 trials
      of each type of inversion moment, but only on one leg. Reliability was assessed
      by comparing left and right leg data within muscle groups for Day 1 testing.
      Repeatability was assessed by comparing Day 1 with Day 2 data. The latency
      measurements (the time between the beginning of the inversion moment and the
      onset of first motor response) for the peroneus brevis and tibialis anterior
      muscles were found to be reliable and repeatable with no significant differences
      between the same muscle groups. The peroneus longus muscle had a significant
      difference between legs but was found to be highly repeatable. Speed of inversion
      moment and plantar flexion angle both caused significant changes in latency
      response of the peroneus muscles, with increased speed producing a shorter
      latency response and increased angle causing a longer latency response. Our
      results indicate a loss of protective reflexes with increasing plantar flexion.

PMID- 8734890
TI  - Proprioception in classical ballet dancers. A prospective study of the influence
      of an ankle sprain on proprioception in the ankle joint.
AB  - We studied prospectively the influence of ankle sprains on proprioception as
      measured by recording the postural sway of classical ballet dancers. Excellent
      balance and coordination are important for classical ballet dancers, and postural
      stability requires adequate proprioception from the ankle joint. Fifty-three
      professional dancers from the Royal Swedish Ballet, Stockholm, and 23
      nonathletes, the control group, participated in the investigation. Postural sway
      was recorded and analyzed with a stabilimeter using a specially designed,
      portable, computer-assisted force plate. Six dancers sustained ankle sprains
      during followup. The recordings were obtained of these dancers before and after
      the injuries. The stabilometry results differed among the male and female dancers
      and the control group as follows: 1) the male dancers demonstrated a smaller
      total area of sway, and 2) both the male and female dancers had a smaller mean
      sway on the left foot than on the right (no mean difference in sway was found
      between the left and right foot in the control group). In comparison with the
      condition before injury and with the uninjured foot, the postural stability of
      the dancer was impaired for several weeks after the ankle sprain. Postural
      stability gradually improved during rehabilitation and improvement still occurred
      several weeks after professional dancing had resumed.

PMID- 8734891
TI  - Biomechanics of iliotibial band friction syndrome in runners.
AB  - We propose a biomechanical model to explain the pathogenesis of iliotibial band
      friction syndrome in distance runners. The model is based on a kinematic study of
      nine runners with iliotibial band friction syndrome, a cadaveric study of 11
      normal knees, and a literature review. Friction (or impingement) occurs near
      footstrike, predominantly in the foot contact phase, between the posterior edge
      of the iliotibial band and the underlying lateral femoral epicondyle. The study
      subjects had an average knee flexion angle of 21.4 degrees +/- 4.3 degrees at
      footstrike, with friction occurring at, or slightly below, the 30 degrees of
      flexion traditionally described in the literature. In the cadavers we examined,
      there was substantial variation in the width of the iliotibial bands. This
      variation may affect individual predisposition to iliotibial band friction
      syndrome. Downhill running predisposes the runner to iliotibial band friction
      syndrome because the knee flexion angle at footstrike is reduced. Sprinting and
      faster running on level ground are less likely to cause or aggravate iliotibial
      band friction syndrome because, at footstrike, the knee is flexed beyond the
      angles at which friction occurs.

PMID- 8734892
TI  - Characteristics of the leg extensors in male volleyball players with jumper's
      knee.
AB  - The aim of the present study was to characterize the performance ability of the
      leg extensor apparatus in a group of athletes with jumper's knee and to compare
      the results with those of a matched control group without knee symptoms. Patient
      and control groups (12 players in each) were selected from a population of 141
      well-trained male Norwegian volleyball players, of which 55 (39%) satisfied the
      diagnostic criteria for jumper's knee. The testing program consisted of a
      standing jump, a countermovement jump, a 15-second rebound jump test, a standing
      jump with a 20-kg load, and a standing jump with a load corresponding to one-half
      of the subject's body weight. Jump height and power were measured using a contact
      mat connected to an electronic timer. The test results of the patient group were
      significantly higher than those of the control group for the countermovement jump
      (15% increase), power during rebound jump (41%), work done in standing jump (12%)
      and countermovement jump (22%), and the difference between countermovement jump
      and standing jump (effect of adding eccentric component). Athletes with jumper's
      knee demonstrated better performance in jump tests than uninjured athletes,
      particularly in ballistic jumps involving eccentric force generation.

PMID- 8734893
TI  - An electromyographic analysis of the shoulder during a medicine ball
      rehabilitation program.
AB  - We used dynamic electromyography and a motion analysis system to describe the
      muscle firing patterns in 10 shoulder muscles and the basic kinematics of a two
      handed overhead medicine ball throw. Ten healthy male subjects with no history of
      shoulder injury were evaluated. The two-handed medicine ball throw was divided
      into three phases for analysis: cocking, acceleration, and deceleration. The
      average duration of the throw was 1.92 seconds; the cocking phase represented
      56%, the acceleration phase 15.5%, and the deceleration phase 28.5% of the throw.
      In the cocking phase, the upper trapezius, pectoralis major, and anterior deltoid
      muscles showed high activity ( > 40% to 60% maximum manual test), and the rotator
      cuff muscles had moderate activity ( > 20% to 40%). In the acceleration phase,
      five of the muscles demonstrated high levels of activity ( > 40% to 60%) and the
      upper trapezius and lower subscapularis muscles had very high levels of activity
      ( > 60%). Analysis of the deceleration phase revealed high activity in the upper
      trapezius muscle and moderate activity in all other muscles except the pectoralis
      major. Our findings support the use of medicine ball training as a bridge between
      static resistive training and dynamic throwing in the rehabilitation of the
      overhead athlete. This training technique provides a protective method of
      strengthening that closely simulates portions of the throwing motion.

PMID- 8734894
TI  - A statistics primer.

PMID- 8734895
TI  - Stimulation of the medial preoptic area of the hypothalamus in the rat elicits
      increases in intracavernous pressure.
AB  - Penile erection can be elicited by various stimuli integrated in the spinal cord
      and/or higher central nervous structures. The medial preoptic area (MPOA) of the
      hypothalamus is known to play a key role in the regulation of the male sexual
      behavior. In anesthetized male rats we performed MPOA stimulation via
      stereotaxically implanted electrodes or canulae delivering L-glutamate. An
      erectile response, assessed by an increase of intracavernous pressure (ICP), was
      recorded during electrical stimulation of the MPOA. Stimulating the posterior
      region of the MPOA elicited a greater erectile response than stimulation applied
      to the anterior region. Microinjections of L-glutamate also elicited an ICP
      increase. Stimulation of MPOA neurons therefore elicits activation of neural
      pathways controlling penile erection.

PMID- 8734896
TI  - Evaluation of cardiorespiratory parameters in rats after spinal cord trauma and
      treatment with NBQX, an antagonist of excitatory amino acid receptors.
AB  - 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), a selective
      antagonist of amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate
      receptors, ameliorates functional deficits and tissue loss after experimental
      contusive spinal cord injury (SCI). Data suggest that NBQX acts via local
      receptors at the injury site. However, potential systemic effects of NBQX could
      also modify consequences of SCI. We therefore examined effects of therapeutic
      doses of NBQX on cardiorespiratory parameters (CRP) including: mean arterial
      pressure, heart rate, respiratory rate and arterial blood gas. We found no
      significant effect on these CRP of either focal microinjection or intravenous
      administration of NBQX at doses that are therapeutic for SCI, in either uninjured
      rats, or rats after SCI. The results support the hypothesis that NBQX affects SCI
      by acting locally rather than through systemic effects and demonstrate NBQX
      treatment paradigms without adverse effects on CRP.

PMID- 8734897
TI  - Expression of markers for both neuronal and glial cells in human amniotic
      epithelial cells.
AB  - Human amniotic epithelial (HAE) cells are formed from amnioblasts, separated from
      the epiblast at about the 8th day after fertilization. We attempted to detect
      various developmental antigens specific to neural cells by immunocytochemical
      methods. The cultured HAE cells displayed positive immunoreactivity to RC1,
      vimentin, A2B5, neurofilament proteins, microtubule-associated protein 2 (MAP2)
      and MAP2 kinase. In addition, the cells also demonstrated immunoreactivity to
      glial fibrillary acidic protein, CNPase, myelin basic protein and
      galactocerebroside. The appearance rate of positive cells was more than 50% in
      cells positive to RC1, A2B5, vimentin or neuronal markers, and 20-30% to glial
      cell markers. Double staining showed the heterogeneous appearance of
      oligodendrocyte lineage cells. These data indicate that HAE cells may have the
      putative multipotentiality of neurons, astrocytes and oligodendrocytes.

PMID- 8734898
TI  - Novel approach to a quantitative treatment of the quantal transmitter release at
      the frog neuromuscular junction.
AB  - To explain the discrepancy between estimates of parameters of quantal transmitter
      release received by different techniques the paper postulates a novel concept for
      quanta mobilization, which assumes that a quantum emitted by a vesicle
      transiently acquires a transition state in which it is immediately available for
      release. The working particle model is formulated in terms of probabilities of
      inter-state quanta transitions. The parameters of the model are determined by
      fitting solutions to the experimental curves representing short-term changes of
      synaptic efficacy at the frog neuromuscular junction as well as taking into
      account the morphologically estimated number of releasable vesicles. The value of
      the model is demonstrated by successful prediction of the estimates of the
      parameters of the quantal transmitter release suggested by evidence received from
      different lines of research.

PMID- 8734899
TI  - EEG coherence within the 13-18 Hz band as a correlate of a distinct lexical
      organisation of concrete and abstract nouns in humans.
AB  - Coherence analysis was applied to the EEG of 19 female participants who had to
      memorize auditorily presented abstract and concrete nouns. The EEG was recorded
      from 19 scalp electrodes (10/20 system). Significant differences between both
      word classes were found only in the beta 1-band (13-18 Hz) whereas the alpha 1
      band (8-10 Hz) revealed coherence patterns which were identical for both word
      classes. These results indicate that the alpha 1-band reflects cognitive
      processes that were common to both word classes, whereas the beta 1-band seems to
      be closely related to associative processes and more complex cognitive functions.

PMID- 8734900
TI  - Supraspinal influences on the facilitation of rat nociceptive reflexes induced by
      carrageenan monoarthritis.
AB  - During hyperalgesia there is an enhancement of wind-up and the appearance of a
      novel wind-up of the A-fibre-mediated responses. We have examined if these
      phenomena are influenced by supraspinal mechanisms by analysing single motor unit
      activity in control and arthritic rats, either intact or acutely spinalised.
      Enhancement of the C-fibre wind-up and the novel A-fibre wind-up were only
      observed in the intact arthritic animals. We conclude that C-fibre wind-up is a
      spinal phenomenon, whereas the enhancement of the C-fibre wind-up and the novel A
      fibre wind-up during arthritis depend also on supraspinal influences.

PMID- 8734901
TI  - Kinetic characterisation and solubilisation of gamma-hydroxybutyrate receptors
      from rat brain.
AB  - The solubilisation of the gamma-hydroxybutyrate (GHB) receptors from rat brain
      membranes was undertaken as the first step for their molecular characterisation
      and purification. Treatment of crude brain membranes with high concentrations of
      NaCl and Triton X-100 resulted in solubilisation of proteins which retain
      specific GHB binding activity. Ionic detergents do not solubilise and/or
      inactivate the receptors. Measurements of kinetic parameters of GHB binding
      showed that the solubilised receptor, in the presence of detergent, exhibited a
      reduction of affinity for GHB and its endogenous brain analogue trans-4
      hydroxycrotonate (T-HCA). The membrane protein extract, submitted to
      chromatography by gel filtration, showed a single peak of protein with [3H]GHB
      binding activity. Association and dissociation constants of GHB for its membrane
      binding site were in accordance with the Kd determined by the Scatchard method.

PMID- 8734902
TI  - Glial fibrillary acidic protein (GFAP) immunohistochemistry in human cortex: a
      quantitative study using different antisera.
AB  - Glial fibrillary acidic protein (GFAP) is the principal marker for brain
      astrocytes. The present study aims to examine the variability in GFAP
      immunohistochemistry in formalin-fixed human brain. Four commercially-available
      antisera were tested using standardised protocols in the cerebral cortex of three
      cases with prominent glial reactions and one control. GFAP immunoreactivity was
      largely confined to the pial surface and white matter in control cortex, with the
      number of astrocytic cell bodies and processes as well as intensity of staining
      markedly increased in damaged cortices. A dramatic difference in the pattern of
      GFAP staining using different antisera was observed and may account for
      discrepancies between past studies. This variance has important practical
      implications for the interpretation of results using GFAP immunohistochemistry in
      human tissue.

PMID- 8734903
TI  - Induction of apoptosis and secondary necrosis in rat dorsal root ganglion cell
      cultures by oxidized low density lipoprotein.
AB  - Neural cell degeneration underlies central and peripheral nervous system
      disorders. In this study we examined the influence of oxidized low density
      lipoprotein (Ox-LDL) on rat dorsal root ganglion (DRG) cells in culture. Methods
      used were cell morphology, lactate dehydrogenase (LDH) release, the TUNEL
      reaction and DNA fragmentation. Exposure of DRG cells to Ox-LDL for 24 h led to
      elevation of LDH in the culture medium; short term exposure (4 h) induced
      apoptosis, evidenced by DNA fragmentation and a positive TUNEL-reaction. DRG
      cells modified LDL in the presence of Cu2+ to mildly oxidized and to a small
      extent to fully oxidized forms; these in situ-generated LDL oxidation products
      were strongly toxic. These results suggest that Ox-LDL is a neurotoxin; it
      initiates apoptotic cell injury which progresses to necrosis and cell death.

PMID- 8734904
TI  - Nitric oxide synthase inhibitor facilitates focal seizures induced by
      aminopyridine in rat.
AB  - The effects of N-nitro-L-arginine (NA), a nitric oxide (NO) synthase inhibitor,
      were investigated on the focal ictal-like seizure induced by 3-aminopyridine in
      rat neocortex in vivo. Intraperitoneal and intracerebroventricular (i.c.v.)
      injections of NA markedly facilitated propagation of epileptiform events. In
      addition, NA injected i.c.v. increased the number/hour of individual ictal
      periods while decreasing their duration. In the presence of NA and an N-methyl-D
      aspartate (NMDA) receptor antagonist D(-)2-amino-5-phosphonovaleric acid (APV)
      the number of ictal periods increased while their duration synergically
      decreased. APV by itself did not change the number of ictal episodes but
      decreased their duration. Our results suggest that NO inhibits the induction and
      propagation of seizure activity. We cannot distinguish the proportion of neuronal
      and/or vascular NO involved in our experimental conditions, but these effects
      seem to be independent of the NMDA receptors.

PMID- 8734905
TI  - The 5-HT1A agonist ipsapirone enhances EEG slow wave activity in human sleep and
      produces a power spectrum similar to 5-HT2 blockade.
AB  - The REM sleep-suppressing effect of postsynaptic 5-HT1A stimulation has been well
      established. Here we investigate the effects of the 5-HT1A agonist ipsapirone (10
      and 20 mg) on sleep EEG power spectra during non-REM sleep in nine healthy
      humans. At the lower dose, slow wave activity (SWA; EEG power in the delta (1-4.5
      Hz) range) was significantly enhanced. At the higher dose, where side-effects
      occurred, the enhancement in SWA was not significant. The spectral profile was
      characterized by a bimodal increase of power in the lower delta and in the theta
      (5-8 Hz) frequencies, and by troughs at 4 Hz and at 11 Hz, a pattern compellingly
      similar to that reported for a 5-HT2 antagonist (seganserin). We propose that the
      spectral data following the lower ipsapirone dose reflect a net decrease of
      neuronal activity at 5-HT2 receptors, mediated through stimulation of
      somatodendritic autoreceptors in the raphe nuclei (presynaptic) and/or through
      stimulation of postsynaptic 5-HT1A receptors colocalized with 5-HT2 receptors.
      The spectral non-REM sleep EEG profile might be used to investigate central 5-HT
      function in humans.

PMID- 8734906
TI  - Corticotropin-releasing factor induction in rat piriform cortex following kainate
      elicited seizures.
AB  - There is a substantial increase in number of cells labeled for corticotropin
      releasing factor-like immunoreactivity in specific extrahypothalamic brain
      regions, particularly the piriform cortex, in rats allowed to survive 24 h
      following generalized clonic seizures. Seizures were elicited by kainic acid.
      Vehicle treated control animals had only a few cells labeled for corticotropin
      releasing factor-like immunoreactivity at these brain sites. These areas of
      corticotropin-releasing factor-like induction appear to be localized to brain
      regions known to be vulnerable to kainate neurotoxicity and cell destruction.

PMID- 8734907
TI  - Hippocampal slices from prion protein null mice: disrupted Ca(2+)-activated K+
      currents.
AB  - The intrinsic properties of hippocampal CA1 pyramidal cells were examined in mice
      lacking prion protein (PrP-null). The resting potentials, time constants,
      amplitude of the medium afterhyperpolarization (AHP) and spike firing
      accommodation did not differ from the control group. The PrP-null group differed
      in having lower input resistances, a lack of the late AHP and of a charybdotoxin
      sensitive summated AHP. We propose that CA(2+)-activated K+ currents, in
      particular IAHP, are disrupted in PrP-null mice.

PMID- 8734908
TI  - The anthozoan neuropeptide Antho-RWamide I modulates Ca2+ current in sea anemone
      myoepithelial cells.
AB  - The anthozoan neuropeptide Antho-RWamide I (< Glu-Ser-Leu-Arg-Trp-NH2) excites
      contraction of endodermal muscles in sea anemones. Single electrode voltage clamp
      recordings from semi-intact preparations of endodermal myoepithelial cells reveal
      that Antho-RWamide I increases an inward Ca2+ current. Evidence for the
      involvement of a Ca2+ current in contraction was supported by the observation
      that Cd2+ abolished spontaneous contractions and reduced inward current.
      Contractions and inward currents induced by Antho-RWamide I were not, however,
      completely abolished in the presence of Cd2+. We conclude that Antho-RWamide, a
      putative neurotransmitter at sea anemone smooth muscle, acts by opening, either
      directly or indirectly, Ca2+ channels in the muscle membrane.

PMID- 8734909
TI  - Neurofibrillary tangles of Alzheimer's disease brains contain 14-3-3 proteins.
AB  - The localisation of 14-3-3 proteins compared to that of tau and ubiquitin-protein
      conjugates in sections of hippocampus from Alzheimer's disease (AD) brains was
      examined by immunohistochemistry. In all cases (n = 10), anti-14-3-3 stained a
      proportion of neurofibrillary tangles (NFT). In general, NFT stained by anti-14-3
      3 were smaller than those stained by anti-tau or anti-ubiquitin-protein
      conjugates and were more confined to the neuronal cell body. Occasionally,
      cortical Lewy bodies in cases of Lewy body dementia were also found to be 14-3-3
      positive. Since 14-3-3 proteins are central to MAP kinase signalling, the results
      support the proposal that this pathway is in part responsible for the
      hyperphosphorylation of tau, which leads to the formation of the paired helical
      filaments seen in AD brains.

PMID- 8734910
TI  - In situ recordings of presumed folliculo-stellate cells in the intermediate lobe
      of the pituitary gland of Xenopus laevis.
AB  - In situ whole cell voltage clamp recordings of presumed folliculo-stellate cells
      were made in the intermediate lobe of the clawed toad Xenopus laevis. Lucifer
      Yellow fillings revealed, in addition to the small, spherical melanotropes, a
      population of larger cells with many processes that were, to a limited extent,
      dye-coupled and are assumed to be folliculo-stellate cells. The presumed
      folliculo-stellate cells differed strongly from the melanotropes in
      electrophysiological properties. The cells had a membrane resistance of < 600 M
      omega (at -100 to -80 mV) and a membrane potential of ca. -90 mV, close to the
      equilibrium potential for K+. At potentials of > or = -20 mV, most of the cells
      displayed a rapidly activating and slowly inactivating outward K+ current. In all
      cells, hyperpolarizing pulses to < or = -100 mV activated an inward rectifying K+
      current.

PMID- 8734911
TI  - Rapid but transient increases in cholecystokinin mRNA levels in cerebral cortex
      following amygdaloid-kindled seizures in the rat.
AB  - Cholecystokinin-octapeptide (CCK-8S) is widely distributed in neurones of the
      central nervous system, where it is thought to act as a transmitter or modulator.
      CCK-8S has been shown to exert anti-convulsant activity in animal seizure models
      and changes in cortical and hippocampal CCK-immunoreactivity and preproCCK
      messenger RNA (mRNA) have been reported following electrically- and chemically
      induced seizures. In the present study, the spatiotemporal effect of amygdaloid
      kindled seizures on levels of preproCCK messenger RNA in rat brain were
      determined using quantitative in situ hybridization histochemistry. Stimulation
      evoked seizures produced bilateral increases (45-70%) in preproCCK mRNA
      throughout layers II-III of the cerebral cortex. These increases were rapidly
      induced, occurring 30-60 min after the last stage 5 seizure, but transient, as no
      significant changes were detected after 2 h, or subsequently at 24 or 72 h, or 2
      8 weeks, post-stimulation. Rapid changes in the relative levels of preproCCK
      mRNA, post-seizure, suggest a possible stabilization of preproCCK transcripts and
      increased production of CCK-8S peptide, which may be involved in anticonvulsant
      mechanisms in response to the acute seizures.

PMID- 8734912
TI  - Comparative sensitivity to adenosine of paired-pulse inhibition and single field
      potentials in the rat hippocampus.
AB  - If excitatory terminals onto inhibitory interneurones were more sensitive to
      adenosine than excitatory terminals onto pyramidal cells in the hippocampus it
      might explain the effect of adenosine to decrease paired-pulse inhibition and
      account for reported excitatory effects of low concentrations of adenosine. We
      have compared the concentration-response relationships for the effect of
      adenosine on single evoked field potentials and on paired-pulse inhibition in the
      CA1 area of the rat hippocampal slice in order to test this hypothesis. Adenosine
      caused a concentration-dependent decrease in both single evoked population spike
      size and in paired-pulse inhibition between potentials. The concentration
      response relationships for both effects was very similar, ruling out the
      possibility that excitatory terminals onto inhibitory interneurones are more
      sensitive to adenosine than excitatory terminals onto pyramidal cells, and
      suggesting that the receptors located at the two sites may be indistinguishable.

PMID- 8734913
TI  - Superantigens.
AB  - Superantigens are potent modulators of the immune system. Some of their
      biological and immunological properties are reviewed here with special attention
      to their potential significance for cutaneous inflammation, specific skin immune
      responses and skin diseases.

PMID- 8734914
TI  - Simultaneously detected aberrant p53 tumor suppressor protein and HPV-DNA
      localize mostly in separate keratinocytes in anogenital and common warts.
AB  - The E6 oncoprotein of human papillomavirus (HPV) is known to inactivate the
      control function on cell cycle exerted by p53 tumor suppressor protein in vitro
      by binding to p53 and thus facilitating the degradation of p53. We have applied a
      simultaneous in situ demonstration method for detecting p53 protein and HPV-DNA
      on formalin-fixed tissue sections, and investigated the in vivo interrelationship
      of p53 protein and HPV-DNA. Immunohistochemical staining for p53 protein with
      polyclonal and monoclonal antibodies, recognizing both wild-type (wt) and mutated
      p53 protein, was performed first and in situ DNA hybridization (ISH) for HPV
      types 6/11 or 16/18 with digoxigenin-labelled probes thereafter. 47% (25/53) of
      48 histologically confirmed primary or recurrent condylomata acuminata (CA), 2
      Bowenoid papulosis (BP) and 3 common wart (CW) biopsies, positive for HPV 6/11 or
      HPV 16/18 DNA, showed keratinocytes immunopositive for p53 protein. Of these, 11
      lesions with abundant numbers of p53-positive cells were further analyzed with
      the double method. Signals for abnormal p53 protein and HPV-DNA were detected in
      separate cell nuclei in all biopsies and, additionally, in the same cell nuclei
      in 3 biopsies (1 BP, 1 CA, 1 CW). Usually the p53 positivity localized more
      basally in the epidermis than HPV-DNA, although p53- and HPV-positive
      keratinocytes were always located closely. The findings were similar for HPV
      types 6/11 and 16/18. Our finding of both p53 and HPV-6/11 signals in the same
      cell nuclei may indicate complexing of p53 and low-risk HPV's without degradation
      of p53. Our results show abnormal p53 expression in HPV-infected skin lesions,
      and suggest that p53 protein is susceptible to aberrations even in the cells in
      the vicinity of productive HPV infection. However, it is not yet fully understood
      how HPV interferes with p53 protein in these cells.

PMID- 8734915
TI  - Interactions of sulfates of divalent metals in nickel-sulfate-sensitive patients.
AB  - 70 nickel-sensitive subjects who previously gave positive patch test response to
      10 microliters of nickel sulfate 0.1 M, were patch tested to 10 microliters of
      mixed aqueous solutions containing nickel sulfate 0.1 M+magnesium sulfate 0.3 M,
      nickel sulfate 0.1 M+zinc sulfate, 0.3 and 0.5 M, respectively, nickel sulfate
      0.1 M+ manganese sulphate 0.3 and 0.5 M, respectively nickel sulphate 0.1 M+
      cadmium sulfate 0.1 and 0.3 M, respectively, nickel sulfate 0.1 M+iron sulfate
      (III) 0.1 and 0.3 M, respectively, and to 10 microliters of aq. cadmium sulfate
      0.1 M, aq. cadmium sulfate 0.3 M, aq. iron sulfate 0.1 M, aq. iron sulfate 0.3 M.
      The results showed that, whilst sulfates of divalent metals with similar size and
      redox properties (Mg, Zn and Mn) were able to reduce or to suppress, in a dose
      dependent way, the majority (75%) of nickel reactions, those with large radius
      and different oxidation state(Fe III), generally gave an increase in the
      reactions. In about 15% of the tested subjects, an increase in all the positive
      reactions to the mixed solutions was found. The findings seem to demonstrate that
      in only a majority but not all of nickel sulfate allergic reactions, is Ni(II)
      able to substitute for divalent ions with similar properties at the ion sites of
      some proteins. This tendency reproduces the results of experimental systems, in
      which nickel toxicity and cancerogenity are considered responsible. In contrast,
      in about 15% of the tested subjects, there was a general enhancement of the
      reactions. In these cases, either the occurrence of a "hyper-irritable" skin
      caused by the adopted test system or, more likely, the formation of Ni complexes
      with different geometries, is hypothesized.

PMID- 8734916
TI  - Thrombin and melittin activate phospholipase C in human HaCaT keratinocytes.
AB  - Following the activation of specific receptors, phospholipase C has been shown to
      cleave the membrane phospholipid phosphatidylinositol bisphosphate into the 2nd
      messengers inositol 1,4,5-trisphosphate and diacylglycerol. Both 2nd messengers
      contribute to the regulation of cellular proliferation. The receptor for
      bradykinin is coupled to this pathway in keratinocytes, but knowledge about other
      activators of phospholipase C is limited. Additional mediators and agents were
      therefore examined regarding their ability to activate phospholipase C in HaCaT
      keratinocytes. Analysis for 3H-inositol phosphates was performed by anion
      exchange HPLC. Thrombin and melittin induced a time- and dose-dependent release
      of inositol 1,4,5-trisphosphate. Several other mediators examined such as
      angiotension II, neurotensin, C3a, pituitary adenylate cyclase activating
      peptide, phenylephrin, and prostaglandin E2, did not induce the formation of
      inositol phosphates. In view of the mitogenic activity and the increased
      formation of thrombin after tissue injury, the coupling of the thrombin receptor
      to phospholipase C in HaCaT keratinocytes suggests a role of this protease in
      epidermal wound healing.

PMID- 8734917
TI  - Heparin induces fibroblast proliferation, cell-matrix interaction and epidermal
      growth inhibition.
AB  - We have examined the effect of heparin on fibroblasts cultivated in monolayer or
      in a 3-dimensional culture system: the so-called collagen lattices. Thereafter,
      we have investigated the effect of heparin on the kinetics of epidermal growth on
      the collagen lattices. In monolayer culture, heparin stimulated the fibroblast
      growth with an optimal response at 0.01 mg/ml. The volume of treated fibroblasts
      was smaller than that of untreated controls. In the collagen lattices, heparin
      stimulated the fibroblast growth with an optimal response at 0.1 mg/ml. The
      volume of treated fibroblasts was greater than that of untreated controls, the
      opposite to the result observed in monolayer culture. The beginning of the
      contraction of the collagen lattices was inhibited by heparin. Heparin inhibited
      epidermal growth on the immersion as well as on the emersion collagen lattices.
      These effects of heparin should be the consequences of heparin-induced
      modifications of cell-matrix interactions.

PMID- 8734918
TI  - Specific detection of anti-cell surface antibodies in herpes gestationis sera.
AB  - We examined 42 herpes gestationis sera with immunofluorescence of normal human
      skin sections, and found that anti-keratinocyte cell surface antibodies were
      detected specifically in 10 herpes gestationis sera. The diagnosis of these
      herpes gestationis cases was confirmed by detecting antibodies against the 180 kD
      bullous pemphigoid antigen with immunoblotting of its fusion protein. The results
      of immunoadsorption assay using baculoproteins of both pemphigus vulgaris and
      pemphigus foliaceus antigens indicated that the herpes gestationis sera did not
      recognize common pemphigus antigens. Immunoblotting of human epidermal extracts
      and immunofluorescence of various tissues also suggested that the sera did not
      recognize any other desmosomal components or paraneoplastic pemphigus antigens.
      The significance of this reactivity is unclear. However, because no control
      bullous pemphigoid sera showed this reactivity, it may suggest a different
      pathophysiology between herpes gestationis and bullous pemphigoid.

PMID- 8734919
TI  - Merkel cells and Merkel cell carcinoma express the BCL-2 proto-oncogene.
AB  - The bcl-2 proto-oncogene, which is involved in the regulation of apoptosis, is
      expressed in a wide variety of fetal and adult tissues. We and others have
      demonstrated recently that in the human skin melanocytes, nervus cells and
      melanoma cells express bcl-2 constitutively. In the present study, we have
      analysed the expression of bcl-2 in Merkel cells and in Merkel cell carcinomas.
      In 2 colour immunofluorescence staining, normal human Merkel cells as identified
      by the expression of cytokeratins 8, 18 and 20, were also anti-bcl-2 positive.
      Staining of paraffin sections of Merkel cell carcinomas with an anti-bcl-2
      monoclonal antibody revealed strong bcl-2 protein immunoreactivity in all 5
      tumors tested. Serial sections of Merkel cell carcinomas stained with the
      monoclonal antibodies CK 20, CAM 5.2, anti-neuron-specific enolase and anti-bcl-2
      showed that the anti-bcl-2 reactive cells were indeed tumor cells. Our data
      demonstrate for the first time, that normal human Merkel cells and Merkel cell
      carcinomas express bcl-2 constitutively. Considering the biological function of
      the bcl-2 proto-oncogene, i.e., its anti-apoptotic effect, it is conceivable that
      in the near future, modulations of the expression of this protein may offer a new
      strategy in the therapy of bcl-2 expressing tumors such as Merkel cell carcinoma.

PMID- 8734920
TI  - Modulation of keratinocyte growth factor (KGF) mRNA expression in human dermal
      fibroblasts grown in monolayer or within a collagen matrix.
AB  - In this study, we analysed the modulation of keratinocyte growth factor (KGF)
      mRNA expression in human dermal fibroblasts cultured either in monolayer or
      within a collagen matrix (dermal equivalent). In monolayer cultures, KGF
      expression by quiescent fibroblasts was stimulated by different growth substances
      such as serum, epidermal growth factor and basic fibroblast growth factor.
      Moreover, we demonstrated that the induction of this gene was mediated by at
      least 2 different signalling pathways involving protein kinase C (PKC) and cAMP.
      In dermal equivalents, we observed that the collagen matrix negatively modulated
      KGF mRNA expression. Indeed, among the growth substances used, only the serum
      slightly stimulated KGF expression. Nevertheless, as in monolayers, this
      induction involved at least PKC and cAMP signalling pathways. As the collagen
      matrix can modulate fibroblast growth, we also studied KGF expression in growing
      fibroblasts from either monolayer cultures or dermal equivalents. We then showed
      that this collagen matrix negatively influenced KGF expression independently of
      the proliferative state of fibroblasts. All these results underline the fact that
      KGF mRNA expression by human dermal fibroblasts is induced by different
      substances; however this expression can be modulated by fibroblast-matrix
      interactions.

PMID- 8734921
TI  - Granulocyte/macrophage-colony-stimulating factor induces the migration of human
      epidermal Langerhans cells in vitro.
AB  - In the present study, we investigated the in vitro migratory activity of human
      epidermal Langerhans cells (LC). Freshly isolated LC exhibit very low spontaneous
      migration. In contrast, a strong migration is recorded 6 h after the isolation.
      This migration is due to the presence of GM-CSF released by surrounding
      keratinocytes in vitro. Picomolar concentrations of GM-CSF promote the migration
      of LC, but nanomolar concentrations are inhibitory. Checker-board experiments
      indicate that GM-CSF acts as a chemokinetic mediator for LC, Bulk cultured LC
      exhibit a significant decrease of their spontaneous migration but retain the
      capacity to respond to GM-CSF only at nanomolar concentrations. In contrast, LC
      cultured in the presence of picomolar concentrations of exogenous GM-CSF exhibit
      a spontaneous migratory activity comparable to that of 6 h rested LC but do not
      respond to GM-CSF. These results suggest that GM-CSF represents an essential
      factor triggering the egress of LC from their epidermal environment.

PMID- 8734922
TI  - Absence of MHC class II antigen on mast cells at sites of inflammation in human
      skin.
AB  - Since the presence of major histocompatibility complex (MHC) antigens has
      recently been reported on murine and human mast cells under various conditions,
      we have investigated their expression on mast cells in different types of
      cutaneous inflammation. Cryostat sections from lesional biopsies of patients with
      psoriasis, atopic eczema, chronic urticaria, lichen planus, bullous pemphigoid
      and urticaria pigmentosa were immunohistochemically stained with monoclonal
      antibodies against MHC class I and class II antigens using a double staining
      APAAP/toluidine blue methodology. While strongly positive staining with the
      antibody directed against MHC class I antigens was found on nearly all mast cells
      in normal skin and in inflammatory dermatoses, reactivity for HLA-DR and HLA-DQ
      antigens on mast cells could not be detected, except for less than 2% of cells
      with doubtful staining. Human mast cells therefore probably play no significant
      role as antigen-presenting cells in the conditions studied.

PMID- 8734923
TI  - [Retrospective detection of hantavirus clinical infections in Argentina].
AB  - Hantavirus activity in rodents and human beings in Argentina has been known since
      the 1980's. In this study, we retrospectively investigated hantavirus infections
      among Argentine Hemorrhagic Fever (AHF) cases notified between 1987 and 1994,
      without virological confirmation. IgG and IgM antibodies to hantavirus were
      tested by ELISA. Among 1028 patients included in the study, we found 13 recent
      infections (1.26%) and 13 remote infections (1.26%). IgG antibodies determined in
      745 healthy persons living in the same localities of recent infection cases, gave
      only one positive result (0.13%). Nine of the 13 recent infections had the
      clinical presentation of Hemorrhagic Fever with Renal Syndrome (HFRS) while the
      other four were in the form of Hantavirus Pulmonary Syndrome (HPS). We performed
      a clinical and epidemiological comparison between the nine patients with FHSR and
      two paired control groups: one with confirmed AHF and the other with Febrile
      Syndrome of Undetermined Etiology (FSUE), which were negative for hantavirus,
      Junin and LCM. There were no differences between clinical signs or symptoms.
      Nevertheless, normal or high leucocyte counts, with thrombocytopenia,
      hemoconcentration, high creatinine levels and proteinuria in HFRS cases resulted
      useful for differential diagnosis. These results showed the coexistence of Junin
      virus and hantaviruses in the endemic area of AHF, and indicate the importance of
      including the infection with these viruses in the differential diagnosis of
      hemorrhagic fevers and respiratory distress syndromes of unknown etiology. The
      clinical variability found could be related to the presence of more than one
      hantavirus serotype in our country.

PMID- 8734924
TI  - Cystic fibrosis: frequency of delta f508 and g542x mutations in Cordoba,
      Argentina.
AB  - Using Polymerase Chain Reaction (PCR) based techniques we analyzed the frequency
      and genotypic distribution of two mutations (delta F508 and G542X) that produce
      Cystic Fibrosis. The study was carried out in 19 non-related patients (38
      chromosomes) born in the Province of Cordoba. The distribution of genotypes
      showed the presence of 8 homozygote patients delta F508/delta F508, 2 individuals
      with non-determined mutations (X/X) and 9 compound heterozygotes (delta F508/X).
      The mutation G542X was not found. The mutation delta F508 was detected in 25
      chromosomes resulting in an incidence of 66%.

PMID- 8734925
TI  - Serological evidence of human Hantavirus infection in Argentina, Bolivia and
      Uruguay.
AB  - A serological survey was conducted in 1985-1987 to determine the presence of
      infection for Hantavirus in the general population in Argentina, Uruguay,
      Paraguay and Bolivia, as well as among rodent-exposed laboratory workers in
      Argentina. Out of 748 individuals tested by immunofluorescence 20 proved positive
      for Hantaan virus 76/118 strain of whom 16 also reacted against Seoul virus 80/39
      strain and 2 against Puumala virus Sotkamo strain. Ten out of 72 Argentine
      laboratory workers were positive for the first 2 viruses by ELISA,
      immunofluorescence and/or plaque reduction neutralization test, in 4 of whom
      recent infection was demonstrated by IgM antibody presence. Inapparent Hantavirus
      infection was thus demonstrated for the first time in 2.7% of regional
      inhabitants, together with 13.9% among rodent-exposed laboratory workers. Our
      data established the existence of human Hantavirus infection nearly 10 years
      before the recognition of clinical cases of hemorrhagic fever with renal syndrome
      and hantavirus pulmonary syndrome in Argentina.

PMID- 8734926
TI  - [Risk factors for the consumption of illegal drugs. Study in 1904 18-year-old
      boys in the city of Buenos Aires].
AB  - During September 1988 an anonymous, self-administered survey was carried out
      among a random sample of 18-year-old boys living in Buenos Aires city. The
      characteristics of 232 boys who reported illegal drug usage during the previous
      year were compared against those of the 1672 who denied drug consumption during
      that period. Forward stepwise multiple logistic regression analysis showed strong
      association between drug use and drug consumption by friends (OR 18.6) or
      brother/sister (OR 4.3), and consumption of tobacco or alcohol (OR 4.5 and 4.2
      respectively). Results show different characteristics that can facilitate the
      primary care physicians' task of prevention and diagnosis of drug consumption in
      his/her patients.

PMID- 8734927
TI  - Body composition in normal and osteoporotic women.
AB  - Body composition and bone mineral density using dual-energy X-ray absorptiometry
      (DEXA) was determined in a large group of normal women and osteoporotic patients
      with atraumatic vertebral fractures. Between the third and seventh decades, there
      was an increase of 9.5 kg of body weight and 7.5 kg of fat mass in the normal
      women. The percentage of fat augmented from 33% to 42%. However, the lean mass
      showed no modifications over these decades. Fat mass in the osteoporotic women
      was significantly less than that in the age and sex matched controls (22.4 +/-
      1.0 vs 26.6 +/- 1.0 kg; p < 0.006). However, lean tissue mass was similar in the
      two groups. The decrease in fat mass explain 74% of the difference of body weight
      between osteoporotics and controls. The fat mass of 13 osteoporotic patients
      (30%) was lower than the lowest value found in the controls and 20(45%) were
      lower than minus one standard deviation of the values for controls. The
      osteoporotic patients had less fat mass in the three subregions evaluated, but
      the difference was more significant in the trunk (-18%) and legs (-17%) than in
      the arms (-11%). Fat mass may have an important protective effect on the
      skeleton. The mechanism has yet to be elucidated.

PMID- 8734928
TI  - [Reproducibility of nuclear grade in breast neoplasm. A multicenter experience].
AB  - Nuclear grade is considered a valuable prognostic factor in mammary carcinomas.
      Since the histological diagnosis of most of these tumors is made by "non expert"
      pathologists, it was considered interesting to find out the reproducibility of
      general pathologists to define the nuclear grade. In order to do this, a series
      of 15 mammary carcinomas, 10 of them randomly selected and 5 because they were
      considered difficult to classify for nuclear grade, were examined separately by
      10 general pathologists. In a first round of observation, each one of them graded
      the cases according to their own criteria as used routinely, and for a second
      round they followed a written guide. An analysis of variance was applied to the
      data and no significant differences were found between observers, neither in the
      randomly selected cases nor in the total series. The written guide, surprisingly,
      instead of lowering the differences, increased them. Analysis of the individual
      performance of observers showed two of them having a great variation between both
      rounds of observation, and this was considered to influence the results of the
      whole group. Interobserver performance to discriminate high grade tumors (G3)
      from the rest, showed a good correlation in all the participants. These results
      allow us to conclude that in this series, examined by general pathologists, an
      acceptable reproducibility was observed, specially when high risk tumors were
      being identified.

PMID- 8734929
TI  - [Effect of magnetic fields on skin wound healing. Experimental study].
AB  - Although there are many publications on the usefulness of magneto-therapy,
      discrepancies exist about the utility of electromagnetic fields in skin wound
      healing. The objective of this work was to study the effect of electromagnetic
      fields on wound healing in rats. Thirty six male Wistar rats were used; a
      rectangular lesion was made in the back of each animal (4.2 cm x 2.3 cm). They
      were divided into 3 groups: group C (control) with sham treatment; group C50,
      treated with continuous electromagnetic fields of 5 mT (50 Gauss) and group P200,
      treated with pulsed electromagnetic fields of 20 mT (200 G). The treatments were
      of 30 minutes a day during 21 days. The corporal weights (Table 1) and the wound
      longitudinal and transversal maximal axis (Figures 1, 2) were weekly recorded and
      the data was evaluated by analysis of variance. On day 14, the P200 group showed
      the maximal longitudinal axis which was smaller than that of group C (p < 0.01).
      On day 21 in both treated groups the maximal longitudinal axis was smaller than
      that of group C (p < 0.01); besides the axis was smaller in the P200 group than
      in the C50 group (p < 0.05). No statistical differences were observed in the
      remaining data. The results showed a facilitating effect of electromagnetic
      fields on wound healing in rats. Pulsed electromagnetic fields seem to have a
      precocious and larger healing effect than continuous electromagnetic fields.

PMID- 8734930
TI  - Multidrug resistant tuberculosis outbreak in Buenos Aires. DNA fingerprinting
      analysis of isolates.
AB  - In order to determine the possible relationship among HIV patients coinfected
      with multidrug resistant tuberculosis strains who had been receiving clinical
      assistance in our Hospital, clinical and epidemiological information from 28
      patients was collected. DNA fingerprinting by restriction fragment length
      polymorphism (RFLP) pattern was performed on the mycobacterial isolates from
      these patients, using the restriction enzyme Pvull and IS 6110 as genetic marker.
      A unique RFLP pattern was found in 10 isolates from 10 different patients who had
      a disease caused by a single strain. Our findings confirm RFLP as a reliable and
      useful tool to analyze TB transmission.

PMID- 8734931
TI  - Hospital transmission of multidrug-resistant Mycobacterium tuberculosis in
      Rosario, Argentina.
AB  - Multidrug-resistant tuberculosis has emerged over the last two years at Carrasco
      Hospital, located in Rosario city. Nosocomial transmission among 7 AIDS patients
      admitted into the same ward between June and December/94 was supported by
      temporal clustering of cases, matching drug susceptibility, and identical IS6110
      fingerprints. Among 8 non-HIV chronic cases without evidence of reciprocal
      contact outside the hospital, two additional clusters of 2 and 4 cases,
      respectively, were identified. The latter was found to be generated by a strain
      genetically related to the one that infected AIDS patients. It is hypothesized
      that an ancestor strain, common to both, might have been brought into the
      hospital long before the outbreak was first suspected.

PMID- 8734932
TI  - [The role of SPARC gene in tumorigenic capacity of human melanoma cells].
AB  - Previous studies from our laboratory have demonstrated that human melanoma cell
      lines and tumors expressed high levels of the extracellular protein SPARC. In
      order to demonstrate its role in human melanoma progression, IIB-MEL-LES human
      melanoma cells were transfected with SPARC full length c-DNA in the antisense
      orientation. In vivo studies demonstrated that all the control mice injected with
      parental cells developed tumors, while none of the mice injected with cells
      obtained from three different clones with diminished levels of SPARC expression,
      developed tumors. These studies suggest that SPARC may play a key role in human
      melanoma progression.

PMID- 8734933
TI  - [Carpal tunnel syndrome as initial manifestation of polymyalgia rheumatica].
AB  - A case of polymyalgia rheumatica with atypical manifestations, including carpal
      tunnel syndrome, distal myalgias and a low eritro sedimentation is reported. The
      association of polymyalgia rheumatica and carpal tunnel syndrome is
      controversial. Although it has been reported previously in a recent and large
      review of carpal tunnel syndrome in Rochester, USA, there was not any more cases
      of polymyalgia rheumatica associated with carpal tunnel syndrome than in the
      general population. In our patient, the symptoms of polymyalgia rheumatica and of
      carpal tunnel syndrome were present at the beginning, and both responded
      satisfactorally to the treatment with methylprednisone. This form of presentation
      and its response to treatment suggest that the symptoms of carpal tunnel syndrome
      are caused by the inflammation of the carpal synovial, which is an unfrequent
      manifestation of polymyalgia rheumatica. We report this case for the purpose of
      altering to an unusual form of presentation of polymyalgia rheumatica in order to
      avoid unnecessary surgery for the carpal tunnel syndrome.

PMID- 8734934
TI  - [Prosthetic valve endocarditis caused by Corynebacterium urealyticum].
AB  - Corynebacterium urealyticum has been recognised as causing inflammatory cystitis
      and other human infections. In our knowledge this is the first case of a
      prosthetic valve endocarditis due to C. urealyticum. It was diagnosed in a 61
      year old male patient with a history of rheumatic fever, hypertension and aortic
      stenosis. He had undergone surgery to replace the aortic valve and to perform
      triple aortocoronary bypass. The isolate was not multiresistant. Endocarditis due
      to C. urealyticum is very rare. Corynebacterium species, usually considered as
      contaminants, frequently colonize surgical cardiovascular areas and must be taken
      into account as causative agents of severe endocarditis.

PMID- 8734936
TI  - [Diarrhea, hypotension, hyponatremia and hypernatruria in AIDS].

PMID- 8734935
TI  - [Medical parathyroidectomy. Its efficacy in treatment of lower maxillary brown
      tumor].
AB  - A patient with end-stage renal disease, hemodialysis treatment, severe secondary
      hyperparathyroidism and mandibular brown tumor received increasing doses of oral
      calcitriol (3.5 to 9 micrograms/week) and calcium carbonate (10 g/day). Nineteen
      months after the treatment, clinical, radiological and humoral improvement were
      observed. The present case demonstrates the effectiveness of medical
      parathyroidectomy for the control of severe secondary hyperparathyroidism--brown
      tumor--in chronic hemodialysed patients. This procedure should be considered as
      choice treatment keeping surgical parathyroidectomy for cases in which it is
      contraindicated such as hyperphosphoremia and/or controlled hypercalcemia or
      failure of the former procedure.

PMID- 8734937
TI  - [Effect of cilazapril, a converting enzyme inhibitor, on cardiovascular
      hypertrophy in the hypertensive patient].
AB  - The sustained increase in peripheral vascular resistance is the hemodynamic
      alteration characteristic of the established adult hypertension. This is the
      result of a vascular tone increase and/or structural changes which imply
      hypertrophy as well as hyperplasia of the vascular smooth muscle fibers,
      hypertrophy of the cardiac cells and an increase in the constituent synthesis of
      the extracellular matrix. Angiotensin II and noradrenalin exert major trophic
      effects which accelerate the progression of cardiovascular hypertrophy being the
      cardiovascular system very sensitive to the trophic actions of renin-angiotensin.
      Angiotensin II induces the expression of the A-chain of the growth factor of
      platelet origin, of the baseline fibroblastic growth factor and of the B
      transformer factor and, moreover, stimulates type I and type III collagen
      synthesis and favors trophic factors release. Therefore, the renin-angiotensin
      system plays an important role in growth regulation and myocyte remodelation and
      in the cardiovascular extracellular matrix which is mediated through specific
      receptors, since it can be inhibited by ATI receptor antagonists for angiotensin
      II and ACE. Cilazapril is an ACE long duration agent which produces a reduction
      of both blood pressure and cardiovascular hypertrophy. This is a multiple action
      mechanism exerting a vasodilator action, inhibiting the sympathetic tone or
      increasing kinine levels and inhibiting the cardiac and vascular renin
      angiotensin system.

PMID- 8734938
TI  - [Non-invasive mechanical ventilation in intensive care].
AB  - Non-invasive mechanical ventilation is useful in order to delay or avoid
      endotracheal intubation. Continuous positive airway pressure (CPAP) is helpful
      for patients with decreased lung compliance, airways obstruction due to vocal
      cord paralysis or tracheobronchomalacia, presence of auto-PEEP (positive end
      expiratory pressure) and as a weaning method. Non-invasive intermittent positive
      pressure ventilation (IPPV) is not very different from conventional mechanical
      ventilation except for the absence of an endotracheal tube. It is specially
      useful in patients with neuromuscular diseases or central hypoventilation. It has
      been also helpful for patients with decrease of lung compliance or COPD and as a
      weaning procedure. It may be applied with or without PEEP and by means of a bi
      level IPPV system. All of these methods require cooperative patients and by means
      of a bi-level IPPV system. All of these methods require cooperative patients and
      they do not allow an adequate management of increased respiratory secretions. Non
      invasive mechanical ventilation has the advantages of not showing complications
      associated to endotraqueal intubation and may be performed by means of less
      expensive equipment.

PMID- 8734939
TI  - [Emerging or re-emerging viruses?].

PMID- 8734940
TI  - [Is multidrug-resistant tuberculosis an emergent infection in Buenos Aires?].

PMID- 8734941
TI  - [Oxygen free radicals and HIV infection. Can antioxidants be useful?].

PMID- 8734942
TI  - [Apoptosis. Its role in the immune system ontogeny and in HIV infection].

PMID- 8734943
TI  - Classification of immature stage habitats of Culicidae (Diptera) collected in
      Cordoba, Argentina.
AB  - In order to classify mosquito immature stage habitats, samples were taken in 42
      localities of Cordoba Province, Argentina, representing the phytogeographic
      regions of Chaco, Espinal and Pampa. Immature stage habitats were described and
      classified according to the following criteria: natural or artificial; size;
      location related to light and neighboring houses; vegetation; water; permanence,
      movement, turbidity and pH. Four groups of species were associated based on the
      habitat similarity by means of cluster analysis: Aedes albifasciatus, Culex
      saltanensis, Cx. mollis, Cx. brethesi, Psorophora ciliata, Anopheles albitarsis,
      and Uranotaenia lowii (Group A); Cx. acharistus, Cx. quinquefasciatus, Cx.
      bidens, Cx. dolosus, Cx. maxi and Cx. apicinus (Group B); Cx. coronator, Cx.
      chidesteri, Mansonia titillans and Ps. ferox (Group C); Ae. fluviatilis and Ae.
      milleri (Group D). The principal component analysis (ordination method) pointed
      out that the different types of habitats, their nature (natural or artificial),
      plant species, water movement and depth are the main characters explaining the
      observed variation among the mosquito species. The distribution of mosquito
      species by phytogeographic region did not affect the species groups, since
      species belonging to different groups were collected in the same region.

PMID- 8734944
TI  - The epidemiology of malaria in Prabis, Guinea-Bissau.
AB  - This article reports upon a community survey of malaria in Prabis, Guinea-Bissau.
      A house to house census of the population was initially carried out from August
      to December 1991 (rainy season). After completing the census of each village, the
      population was invited to come, a week later, to a central point, where they were
      medically examined and finger-prick blood samples were collected for
      epidemiological characterization of the malaria situation in the area. The blood
      films of the one single village were used to compare the sensitivity and
      specificity of Polymerase Chain Reaction (PCR) with optical microscopy detection
      of parasites. In another village, the occurrence of parasitaemia was compared in
      children with and without fever. During the dry season, from March to June 1992,
      the population in each village was again invited to come to a central point. Some
      of the field procedures were repeated. The study revealed Prabis as an
      administrative Sector of Guinea-Bissau with endemic malaria, mostly due to
      Plasmodium falciparum, but with a significant rate of mixed infections. Active
      transmission occurred throughout the year, but it was more intensive during the
      rainy season and in the northwestern quadrant of the Sector. The level of
      endemicity of the village varied from hypo to holoendemic. The factors associated
      with the differences among villages included village size and predominant
      economic activity (closeness to rice fields). The transmission paradigm was, most
      likely, a mixture of malaria of the African wet Savannah and malaria associated
      with irrigated paddy fields. PCR proved to be a sensitive method with low
      specificity during the dry season. Pyraexia of 37.4 degrees C or higher in
      children aged 2-9 years is not a sensitive indicator of parasitaemia but, it is
      highly specific and it has a clinically useful predictive value.

PMID- 8734945
TI  - Natural infection of a domestic cat (Felis domesticus) with Leishmania (Viannia)
      in the metropolitan region of Belo Horizonte, State of Minas Gerais, Brazil.

PMID- 8734946
TI  - Monoclonal antibodies for the identification of New World Leishmania species.
AB  - Monoclonal antibodies specific for selected species complexes of Leishmania have
      been employed for the characterization of several representative strains of
      Leishmania isolated from different hosts and localities in the Americas. In the
      past 15 years, data have been accumulated concerning (i) the specificities of a
      number of these monoclonal antibodies and (ii) the antigenic variation (level of
      the expressed antigenic determinants) occurring among New World Leishmania
      species or strain variants as recognized by the monoclonal antibodies. This
      report is an attempt to summarize in brief the data accumulated to date on these
      points and to indicate the directions for future applications of these specific
      monoclonal antibodies for identification of leishmanial isolates.

PMID- 8734947
TI  - Variation between geographical populations of Lutzomyia (Nyssomyia) whitmani
      (Antunes & Coutinho, 1939) sensu lato (Diptera:Psychodidae:Phlebotominae) in
      Brazil.
AB  - Phylogenetic analysis of morphometric and biological characters indicated that
      there are two distinct forms of Lutzomyia whitmani in Brazil: one is present both
      north and south of the River Amazonas in the State of Para while the other occurs
      in northeast Brazil, in the State of Ceara, and further south, including the type
      locality in State of Bahia. The Amazonian form is reportedly neither strongly
      anthropophilic nor synanthropic, and it is the vector of Leishmania shawi;
      whereas the southern form is often collected peridomestically, while biting man,
      and has been found infected with Le.(V.) braziliensis. The ratio of the length of
      the genital filaments to that the genital pump was found to be consistently
      smaller in males of the Amazonian populations. A middle repetitive DNA element
      was isolated by differentially screening a genomic library made using Amazonian
      material, and the sequence was diagnostic for this form of Lu. whitmani (being
      absent or occurring in low copy number in the southern form). The total evidence
      suggests there are at least two, geographically-isolated forms of Lu. whitmani,
      which may represent different cryptic species.

PMID- 8734948
TI  - Synhimantus (Synhimantus) magnipapillatus n. sp. (Nematoda, Acuarioidea) from the
      Yellow-crowned Night-heron, Nyctanassa violacea cayennensis (Gmelin) (Aves,
      Ardeidae).
AB  - Synhimantus (Synhimantus) magnipapillatus n. sp., mainly considering the
      outstanding size of the cervical papillae and the delicate structure of the
      cephalic cordons, is not related to any other species of the genus, except for S.
      (S.) laticeps, concerning the similarities regarding the spicules, that justify
      their comparison.

PMID- 8734949
TI  - Complete immunization against Trypanosoma cruzi verified in individual mice by
      complement-mediated lysis.
AB  - Experimental systems to assay immunity against Trypanosoma cruzi usually
      demonstrate partial resistance without excluding the establishment of sub-patent
      infections in protected animals. To test whether Swiss mice immunized with
      attenuated parasites might develop complete resistance against virulent T. cruzi,
      experiments were performed involving challenge with low numbers of parasites,
      enhancement of local inflammation and the combination of natural and acquired
      resistance. Absence of infection was established after repeated negative
      parasitological tests (including xenodiagnosis and hemoculture), and lack of
      lytic antibody was tested by complement mediated lysis. Immunization with 10(7)
      attenuated epimastigotes conferred protection against the development of high
      levels of parasitemia after challenge with Tulahuen strain, but was unable to
      reduce the number of infected animals. However, when a strong, delayed-type
      hypersensitivity reaction was triggered at the site of infection by injecting a
      mixture of virulent and attenuated T. cruzi, a significant proportion of
      immunized animals remained totally free of virulent infection. The same result
      was obtained when the immunization experiment was performed in four month old
      Swiss mice, displaying a relatively high natural resistance and challenged with
      wild, vector-borne parasites. These experiments demonstrate that complete
      resistance against T. cruzi can be obtained in a significant proportion of
      animals, under conditions which replicate natural, vector delivered infection by
      the parasite.

PMID- 8734950
TI  - Assessment of immunity induced in mice by glycoproteins derived from different
      strains and species of Leishmania.
AB  - A comparative study was undertaken on the immunogenic properties of 63kDa
      glycoproteins obtained from five different strains/species of Leishmania and
      assessed in C57BL/10 mice. The humoral immune response was assessed by ELISA
      against the five different antigens of the immunized animals. The cellular immune
      response was derived from Leishmania. The response was found to be species
      specific in all of determined by means of the cytokine profiles secreted by the
      spleen cells of immunized animals. The presence of gamma-IFN and IL-2, and the
      absence of IL-4 in the supernatants of cells stimulated by L. amazonensis antigen
      established that the cellular response is of Th1 type. The five glycoproteins
      tested were equally effective in protecting C57BL/10 mice against challenge by L.
      amazonensis. About 50% of the immunized animals were protected for six months.

PMID- 8734951
TI  - Recrudescence induced by cyclophosphamide of chronic Trypanosoma cruzi infection
      in mice is influenced by the parasite strain.
AB  - Reactivation of chronic chagasic patients may occur upon use of immunosuppressive
      drugs related to kidney or heart transplantation or when they are affected by
      concomitant HIV infection. This recrudescence, however, does not occur in all
      chagasic patients exposed to immunosuppressive agents. We therefore investigated
      the influence of Trypanosoma cruzi strains in the recrudescence of the parasitism
      in mice at the chronic phase treated with cyclophosphamide, an immunosuppressor
      that blocks lymphocytes DNA synthesis and therefore controls B cells response. A
      large variation was detected in the percentages of newly established acute phases
      in the groups of mice inoculated with the different strains. We suggest that
      reactivation of chronic T. cruzi infections is influenced by the parasite
      intrinsic characteristics, a phenomenon that might occur in the human disease.

PMID- 8734952
TI  - The sand fly fauna (Diptera: Psychodidae: Phlebotominae) of a focus of cutaneous
      leishmaniasis in Ilheus, State of Bahia, Brazil.
AB  - The municipality of Ilheus, State of Bahia, has a focus of cutaneous
      leishmaniasis where entomological studies were carried out to determine the sand
      fly species and their habits. Lutzomyia migonei, L. sallesi, L. tupynambai, L.
      schreiberi, L. intermedia, L. whitmani, L. yuilli yuilli, L. fischeri, L.
      pessoai, L. shannoni and L. misionensis were identified. Lutzomyia whitmani was
      the predominant species. Specimens were collected indoors, at peridomestic sites,
      in the cocoa plantations and in other types of collections. Females fed readily
      on humans and were attracted to domestic animals. Our evidence suggests that L.
      whitmani is a probable vector.

PMID- 8734953
TI  - Trypanosoma rangeli and trypanosoma cruzi: cross-reaction among their immunogenic
      components.

PMID- 8734954
TI  - Diagnosis of malaria by acridine orange fluorescent microscopy in an endemic area
      of venezuela.
AB  - Fluorescent (acridine orange) microscopical examination of capillary centrifuged
      blood (quantitative buffy coat [QBC] analysis) and Giemsa stained thick blood
      smears (GTS) were compared for diagnosis of malaria in blood specimens from
      adults living in malaria transmission areas of the States of Bolivar and Amazonas
      in southeastern and south Venezuela, respectively. Of a total of 198 GTS
      examined, 95 subjects (48%) showed parasitaemia. Among the 95 blood films with a
      positive GTS, 94 were judged positive by the QBC. However, positive QBC tubes
      were found in 29 out of 103 blood specimens with a negative GTS. Thus, relative
      to a GTS standard, the sensitivity and specificity of the QBC-test was 99.2% and
      72%, respectively. Young trophozoites of Plasmodium vivax and P. falciparum could
      not be distinguished with certainty. It is confirmed that the QBC offers many
      advantages compared with the standard diagnosis of malaria parasites,
      specifically in the speed of staining and ease of interpretation. However, in
      places where P. falciparum and P. vivax occur, species and stage differentiation
      should be confirmed with the GTS.

PMID- 8734955
TI  - Trypanosoma cruzi defined antigens in the serological evaluation of an outbreak
      of acute Chagas disease in Brazil (Catole do Rocha, Paraiba).
AB  - Immunoglobulin G and M humoral response to recombinant protein B13 and
      glycoconjugate LPPG Trypanosoma cruzi defined antigens was evaluated by ELISA in
      18 patients in the acute phase of Chagas disease, who were contaminated on the
      same occasion. LPPG showed 100% positivity detecting both IgM and IgG antibodies,
      while positivity of 55-65% was observed for B13. An epimastigote alkaline extract
      (EPI) also showed high sensitivity for acute IgM (100%) and IgG (90%) antibodies.
      However LPPG had better discriminatory reactivity since with EPI two patients
      showed negative IgG, and several other sera presented OD values for IgG and IgM
      antibodies very close to the cutoff. Thus, it is suggested that detection of IgM
      antibodies by LPPG may be used for diagnosis of the acute phase of Chagas
      disease. An intense decline of IgG and IgM antibodies to the three antigens was
      observed in response to anti-T. cruzi chemotherapy in all acute phase patients.
      After treatment, six (30%) individuals maintained IgG positivity to EPI, LPPG,
      and B13 with lower reactivity than that measured at the acute phase. For
      comparison, serology of a group of 22 patients in the chronic phase of Chagas
      disease and also submitted to chemotherapy was determined. Positive IgM
      antibodies to EPI, LPPG and B13 were detected in only 5-9% cases. In all chronic
      phase patients IgG antibodies highly reactive to the three antigens were present
      and no significant decrease resulted after benznidazole administration. These
      observations reinforce previous reports that treatment in the acute phase may
      reduce or eliminate the parasite.

PMID- 8734956
TI  - Detection by ultrasound of living adult Wuchereria bancrofti in the female
      breast.

PMID- 8734957
TI  - Use of the 2,3-diacyl-trehalose and the purified protein derivative in the
      serodiagnosis of tuberculosis in AIDS.
AB  - The effect of the human immunodeficiency virus (HIV) infection on IgG production
      against purified protein derivative (PPD) and 2,3-diacil-trehalose (SL-IV) was
      investigated by an enzyme-linked immunosorbent assay (ELISA) test. Comparison
      between the antigens showed that immunocompetent patients produce preferentially
      antibodies to SL-IV than to PPD (73.3% versus 63.3%). Combination of these
      results showed an increase of the sensitivity to 80%, which decreased over the
      spectrum of immunodepression caused by HIV. In the tuberculous HIV seropositive
      group the sensitivities of SL-IV and PPD were 36.4% versus 40% and 0% versus
      22.2% in the tuberculosis/acquired immunodeficiency syndrome (TB/AIDS) group.
      Combination of these results gave respectively 54.5% and 20%, showing that
      serological tests have limited value for diagnosis of tuberculosis in HIV
      infected patients. High antibody levels were observed in HIV seropositive
      asymptomatic group, but only two individuals were positive for both antigens. In
      the follow up, one of them developed tuberculous lymphadenitis, indicating that
      further work is needed to access the value of serological tests in predicting
      tuberculosis in HIV infected individuals.

PMID- 8734958
TI  - Analysis of the clonal diversity of Staphylococcus aureus methicillin-resistant
      strains isolated at Joao Pessoa, state of Paraiba. Brazil.
AB  - To investigate the clonal diversity of Staphylococcus aureus strains isolated at
      Joao Pessoa, State of Paraiba, Brazil, digested genomic DNA were studied by
      pulsed-field gel electrophoresis (PFGE) in nine methicillin-resistant strains
      (MRSA) and three methicillin-sensitive strains (MSSA), selected among 67 isolates
      based on their antimicrobial susceptibility and epidemiology. The isolates were
      obtained between April and November 1992 from the Hospital of the Federal
      University of Paraiba, located in Joao Pessoa. Two MRAS isolates from the Oswaldo
      Cruz Hospital, Sao Paulo, Brazil, including an epidemic strain previously
      detected from different hospitals at the country were used as control. Five
      different patterns, were demonstrated by MRSA isolated in Joao Pessoa and these
      patterns were described in several epidemiologically unrelated hospitals in Sao
      Paulo. Our results suggest the interstate dissemination of a MRSA clone in Joao
      Pessoa which is similar to that described in other cities of Brazil.

PMID- 8734959
TI  - Hemolytic activity of Trichomonas vaginalis and Tritrichomonas foetus.
AB  - The hemolytic activity of live isolates and clones of Trichomonas vaginalis and
      Tritrichomonas foetus was investigated. The isolates were tested against human
      erythrocytes. No hemolytic activity was detected by the isolates of T. foetus.
      Whereas the isolates of T. vaginalis lysed erythrocytes from all human blood
      groups. No hemolysin released by the parasites could be detected. Our preliminary
      results suggest that hemolysis depend on the susceptibility of red cell membranes
      to destabilization and the intervention of cell surface receptors as a mechanism
      of the hemolytic activity. The mechanism could be subject to strain-species
      genera specific variation of trichomonads. The hemolytic activity of T. vaginalis
      is not due to a hemolysin or to a product of its metabolism. Pretreatment of
      trichomonads with concanavalin A reduced levels of hemolysis by 40%.

PMID- 8734960
TI  - N-terminal amino acid sequences of the major outer membrane proteins from a
      Neisseria meningitidis group B strain isolated in Brazil.
AB  - The four dominant outer membrane proteins (46, 38, 33 and 28 kDa) were detected
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in a semi
      purified preparation of vesicle membranes of a Neisseria meningitidis (N44/89,
      B:4:P1.15:P5.5,7) strain isolated in Brazil. The N-terminal amino acid sequence
      for the 46 kDa and 28 kDa proteins matched that reported by others for class 1
      and 5 proteins respectively, whereas the sequence (25 amino acids) for the 38 kDa
      (class 3) protein was similar to class 1 meningococcal proteins. The sequence for
      the 33 kDa (class 4) was unique and not homologous to any known protein.

PMID- 8734961
TI  - Anti-moulting activity in Brazilian Melia azedarach.

PMID- 8734962
TI  - Ultrastructure of cell renewal in the midgut of termites.

PMID- 8734963
TI  - [Behavior of caliptrate Diptera in relation to oviposition substrates under
      laboratory conditions in Rio de Janeiro, RJ, Brazil].
AB  - How adult females of calyptrate Diptera recognize the appropriate breeding
      substrate is a matter of controversy. Among holometabolic insects, the feeding
      opportunities of immature stages are generally determined by the adult female
      choice of an oviposition site. The ovipositional and larvipositional substrate
      preference for the synanthropic flies (Chrysomya megacephala, C. putoria,
      Phaenicia cuprina: Calliphoridae; Atherigona orientalis, Synthesiomyia nudiseta:
      Muscidae; Ravinia belforti, Parasacophaga ruficornis, Peckia chrysostoma:
      Sarcophagidae) is presented in this work. The substrate used for testing were the
      following: bovine minced meat, fish (sardine), bovine liver, shrimp, squid, human
      faeces and banana. Bovine minced meat was the ovipositional and larvipositional
      substrate preferred by seven species. Human faces were preferred by R. belforti.

PMID- 8734964
TI  - Feeding preference of the larvae of Chrysomya megacephala (Fabricius) (Diptera:
      Calliphoridae) and Ravinia belforti (Prado e Fonseca) (Diptera: Sarcophagidae)
      concerning different diets.

PMID- 8734965
TI  - [The university and electronics].

PMID- 8734966
TI  - Analysis of antidiarrhoeic effect of plants used in popular medicine.
AB  - People customarily use the extracts of plants known to have antidiarrhoeal
      effects without any scientific base to explain the action of the extract. For
      this reason, an investigation was undertaken with a view to determining the
      efficacy of the effects of the brute aqueous extract (BAE) of the leaves of
      Psidium guajava (guava), Stachytarpheta cayenensis (bastard vervain), Polygonum
      punctatum (water smartweed), Eugenia uniflora (Brazil or Surinam cherry) and
      Aster squamatus (ze-da-silva) on the intestinal transport of water in rats and on
      the gastrointestinal propulsion in mice. With the exception of the BAE of S.
      cayenensis, all other BAE's have increased the absorption of water in one or more
      intestinal portion in relation to the control group. All tested BAE, except that
      of P. punctatum, reduced the gastrointestinal propulsion in relation to that of
      the control group. The results indicate that the BAE of the leaves of P. guajava,
      S. cayenensis, P. punctatum, E. uniflora and A. squamatus have a potential
      antidiarrhoeic effect to be confirmed by additional investigations in animals
      infected with enteropathogenic agents.

PMID- 8734967
TI  - Mortality from asthma in the state of S. Paulo, Brazil (1970-1992).
AB  - Mortality from asthma has shown important variations over time in several
      countries. In Brazil, a mortality study performed in the 60s, covering the cities
      of S. Paulo and Ribeirao Preto, and other ten cities showed that S. Paulo
      presented the lowest death rate from asthma among of them all. It was decided to
      study the time trends of deaths from asthma and from the whole set of respiratory
      diseases from 1970 to 1992, in the population aged 15-34 yrs. old in the State of
      S. Paulo, as well as to compare them with those of other countries. Asthma
      mortality rates during the 23 years of observation since 1975, showed an
      oscillatory declining pattern with a peak of deaths in the initial years. The
      linearization of the curve allows the calculation of Pearson's correlation
      coefficient that was significantly negative, suggesting a decline in the
      mortality over this period, mainly in the 5-9 yrs. old and 30-34 yrs. old strata.
      The segmentation of data between the period of ICD-9, 1970 to 1978, and of ICD-9,
      1979 and subsequent years, shows that there is stability within each period, in
      all age-groups, except for that of 5-9 yr. olds between 1970-1978. Comparing the
      rates of the population aged 15-34 yrs. old for the State of S. Paulo, Brazil,
      with trends observed in 14 other countries, an intermediate pattern for the first
      triennial period (1970-1972) as well as for the subsequent triennial periods,
      emerges. A prevalence study of asthma, a follow up program meant for using
      emergency rooms and a surveillance of deaths due to all respiratory diseases and
      specifically to asthma are strongly recommended.

PMID- 8734968
TI  - Rise and fall in ischemic heart disease mortality - it may have happened before.
AB  - The rise in ischemic heart disease (IHD) mortality occurring mostly during the
      first half of the 20th century is usually associated with economic development
      and its consequences for people's lifestyles. On the basis of historical
      evidence, it is postulated that a previous IHD epidemic cycle may have occurred
      in England and Wales towards the turn of the nineteenth century. The implications
      of this on causal theories and current etiological research on atherosclerosis
      are discussed.

PMID- 8734969
TI  - Cognitive deficit and depressive symptoms in a community group of elderly people:
      a preliminary study.
AB  - Since the number and proportion of old people increases worldwide, health
      professionals and systems should be made aware and prepared to deal with their
      problems. Cognitive deficit and symptoms of depression are common among the
      elderly, and may occur in relation to various risk factors such as health
      conditions and psychosocial variables. In order to study cognitive deficit and
      the presence of signs and symptoms of depression, 62 elderly community subjects
      enrolled at a Community Health Unit in Porto Alegre, southern Brazil, were
      interviewed. They were evaluated by means of the Mini Mental State Exam, the
      Montgomery-Asberg Depression rating scale, and a questionnaire on health
      conditions, living arrangements and social variables. Higher levels of symptoms
      of depression were observed among subjects exposed to major risk factors for
      cerebrovascular diseases (diabetes and coronary disease), while impaired
      cognitive performance was seen among individuals who could not count on the
      presence of a confidant (social network variable). The results suggest that the
      early identification of major risk groups among old people can help to prevent
      institutionalization and keep individuals in the community.

PMID- 8734970
TI  - [Estimates of infant mortality in Brazil in the 80's: a proposal for a
      methodological procedure].
AB  - A procedure for the estimation of the infant mortality rate in Brazil, in the
      1980's, based only on the age distribution of registered deaths, is here
      proposed. Using this technique, it is possible to estimate the probabilities of
      dying in the first year of life in a continuous way, year by year, for different
      regions of the country. The space-time distribution of the main causes of infant
      deaths is analysed and the relevance of using this coefficient to express the
      social and economic conditions of the Brazilian population from 1979 to 1989 is
      discussed.

PMID- 8734971
TI  - [Nutritional and feeding status of preschool children in the semi-arid region of
      Bahia (Brazil): I. Anthropometric assessment].
AB  - A survey of 754 preschool children was undertaken in the urban areas of seven
      small towns of the semi-arid region of Bahia, Northeast Brazil. The study set out
      to determine the prevalence of weight and height deficits, as well as to
      correlate them with variables such as age, family income, mother's schooling and
      food consumption. A prevalence of 22.9% of Height for Age (HA) below -2.0 SD was
      found (stunting) and prevalence of 19.1% and 3.6% were determined, respectively
      for Weight for Age (WA) and Weight for Height (WH) below -2.0 SD (wasting).
      Regarding food consumption, only 6.8% of the children received a diet with an
      adequate energy supply for their age group in the previous day. There was a close
      association between inadequate HA and WA and family income per capita (p = 0.001
      and p = 0.000, respectively). Children from families with income < 1/4 of the
      minimum wage per capita had twice the chance of being malnourished as compared
      with those from the > or = 1/2 minimum wage per capita stratum. The children
      included in this study showed prevalences of inadequate WH and WA significantly
      higher than those found in a national survey conducted in the same period (p =
      0.047 and p = 0.000 respectively). This fact is surprising since in the last
      decade important reductions in child malnutrition and mortality were reported in
      the country as a whole; this may indicate that children from this region probably
      were not benefitted in the same way as the rest of the Brazilian child
      population.

PMID- 8734972
TI  - [Occurrence of Campylobacter spp among food handlers in hospital kitchens in
      urban areas of the southern region of Brazil].
AB  - The lack of information regarding the occurrence of Campylobacter spp in food
      handlers and the potential public health risk involved, led to the undertaking of
      this work. The main purpose was to verify the presence of asymptomatic
      Campylobacter spp carries in food handlers of hospital and commercial foodservice
      kitchens. The average prevalence of carriers in kitchens was of 6.2%; that in
      commercial foodservice kitchens (10.5%) being higher than that found in hospital
      kitchens (2.2%) in a universe of 177 individuals studied. A close relationship
      was found between Campylobacter spp, carriers of masculine sex and age group,
      which was of about 20 to 35 years of age. There was also strong evidence
      suggesting a higher prevalence of Campylobacter spp among handlers of masculine
      sex than among those of feminine sex.

PMID- 8734973
TI  - [Occupational noise exposure and hypertension].
AB  - The hypothesis that occupational noise exposure is positively associated with
      hypertension was examined in a cross-sectional study carried out on a group of
      patients who were enrolled at the Occupational Health Unit of the Unified Health
      System, situated in Salvador city, the capital of Bahia state, Brazil. Data were
      obtained from 276 medical records, corresponding to all patients newly registered
      during the first six months of 1992. Data on noise exposure come from both
      reported occupational exposure history and clinical diagnosis of occupational
      noise-induced hearing loss. Hypertension diagnosis complies with World Health
      Organization criteria, as well as with the history of antihypertensive treatment.
      Stratified analysis and unconditional logistic regression modeling show results
      that do not support the study hypothesis: there are no differences between
      systolic or diastolic blood pressure or between proportion of hypertension for
      exposed and non exposed groups. However, statiscally significant (alpha = 0.05)
      increment of the effect measured was reported among workers who reported low
      educational level (below elementary). This could be another evidence of socially
      related inequalities underlying exposure distribution among workers at the
      workplace, which should be addressed, at greater depth, in future studies.

PMID- 8734974
TI  - [Alberprosenia malheiroi Serra, Atzingen & Serra, 1987 (Hemiptera, Reduviidae).
      Redescription and bionomics].
AB  - Alberprosenia malheiroi n. sp. first became known through an informal publication
      of a paper submitted a Congress, in 1980. The same diagnosis with a photograph
      was published in 1987, but no formal description has yet been made. The present
      authors describe adults and immature instars, establish a sintypical series and
      introduce bionomic data and data on the rearing of this species in insectary. The
      most evident differences between A. malheiroi n. sp. and A. goyovargasi, the
      former generic species, are the general colour pattern which is completely black;
      the interocular area, wider than an eye in dorsal view; the acute apex in collar
      tubercules and the significantly larger size, almost double that of the latter
      specie. The eggs are small attach themselves to the substratum in groups of
      either 3 or 4, are elipsoid with no lateral flattening, having a convex and
      prominent operculum, without conspicuous structures. Nymphs have the typical
      tribal and generic characteristics in each stage, the anteocular region being
      shorter than the postocular one. Pilosity appears in the second instar and
      becomes more evident with instar development. A. malheiroi n. sp. was captured in
      a forest, in wild (palm-tree) ecotopes associated with bats or birds, in the
      State of Para, Brazil. Trypanosoma cruzi was not found in any specimens. These
      triatomines were reared in +/- 25 degrees C and +/- 60% RH, the insects are quick
      and fly without difficulty. They fed well on pigeons and bats but not on rats,
      mice or hamsters. The eggs incubation period was thirteen days on average, and
      the evolution time of the nymphal period was a hundred and thirty two days on
      average.

PMID- 8734975
TI  - [Excretion of promastigotes of Leishmania pifanoi by experimentally infected
      Lutzomyia youngi].
AB  - The increase in the promastigotes population of Leishmania pifanoi in Lutzomyia
      youngi experimentally infected and kept on 50% sacarose under constant conditions
      of temperature and humidity is described. Two stages in the differentiation and
      growth of the parasites are recognised between two and twenty-four hours after
      meals. The pleomorphic differentiation of the amastigotes in short promastigotes
      which multiply by binary division for 60 hours, when the rupture of the
      peritrophic membrane occurs, takes place within 48 hours. The second stage occurs
      between 72 and 96 hours when some of the parasites migrate to the esophagic valve
      and the rest of the free parasites are excreted in fecal drops as large, active
      promastigotes. The first drops excreted react positively to glucose or contain
      crystals of urate. The excess promastigotes of the second stage of development
      are eliminated in the last excretions and react positively to the Hemoscreen and
      Biuret tests for total proteins as also for glucose and account for 82% of the of
      drops excreted. The excretion of parasites by Lu. youngi is a normal stage in the
      growth of L. pifanoi into a vector.

PMID- 8734976
TI  - [Amplified chemical disasters: a challenge for public health].
AB  - Chemical accidents involving explosions, large fires and leakages of hazardous
      substances occurring during transport, storage and industrial production of
      chemicals constitute a real challenge to health, environmental and industrial
      safety professionals. The aim of this article is to discuss the main questions
      that this kind of accident provokes, in terms of public health, particularly in
      developing countries such as Brazil. The paper defines and characterises these
      accidents and the various health risk they involve excluding the leakages of
      hazardous substances during "normal" production in industry--through the
      combination of quantitative and qualitative information drawn from the
      international literature on the subject. From some examples of chemical accidents
      such as occurred in Bhopal (India), Vila Soco (Brazil), Sao Paulo (Mexico) and
      data of the World Health Organization (WHO), the authors seek to show that these
      events present a worsening, in terms of immediate deaths and injuries, in
      developing countries. The statistics of chemical accidents which occurred during
      the last ten years (1984 to 1993) in the State of Rio de Janeiro are used taken
      as a frame reference for the purpose of bringing to light the great number of
      occurrences made with no registration of basic information regarding assessment
      or surveillance. The complexity of causes and consequences, together with the
      structural problems of developing countries, present public health professionals
      and institutions, with some important tasks especially those of health risk
      assessment and the formulation of strategies to prevent and control future major
      chemical accidents.

PMID- 8734977
TI  - Membrane potential difference and intracellular cation concentrations in human
      placental trophoblast cells in culture.
AB  - 1. The electrochemical gradients for Na+ and K+ were assessed in a cell culture
      model of trophoblast differentiation. 2. Membrane potential difference (Em),
      intracellular water and Na+ and K+ contents were measured in choriocarcinoma
      cells (JAr cell line; 96% of which are undifferentiated trophoblast cells) and in
      mononucleate and multinucleate (differentiated) cytotrophoblast cells isolated
      from the human placenta at term. 3. There was a significant fall in Em from -57
      mV in JAr cells, to -48 and -40 mV in mono-and multinucleate cytotrophoblast
      cells, respectively. Treatment with ouabain (1 mM for 15 min) depolarized the JAr
      cell membrane by 15 mV but did not affect cytotrophoblast cell membrane
      potential. 4. Intracellular K+ concentration was similar in JAr, mono- and
      multinucleate cytotrophoblast cells but Na+ concentration was higher in
      mononucleate cytotrophoblast cells compared with JAr cells. 5. Ouabain treatment
      (3 mM for 15 min) caused a small increase (4.5%) in cell water in mononucleate
      cytotrophoblast cells but lowered K+ (approximately 30%) and increased Na+
      concentration (approximately 125%) in all the trophoblast cells studied. 6. The
      K+ equilibrium potential (EK) was more negative than Em in all cells and the
      difference between EK and Em was smaller in JAr cells (-25 mV) than in mono- and
      multinucleate cytotrophoblast cells (-33 and -43 mV, respectively). 7. The Na+
      equilibrium potential (ENa) was positive in the trophoblast cells and the
      difference between ENa and Em was 122, 100 and 100 mV in JAr, mono- and
      multinucleate cytotrophoblast cells, respectively. 8. These results suggest that
      the electrochemical gradient for K+ is affected by the stage of trophoblast cell
      differentiation. In contrast, the electrochemical gradient for Na+ is similar in
      mono- and multinucleate cytotrophoblast cells.

PMID- 8734979
TI  - Unloaded shortening velocities of rabbit masseter muscle fibres expressing
      skeletal or alpha-cardiac myosin heavy chains.
AB  - 1. Some rabbit masseter fibres express the alpha-cardiac myosin heavy chain
      (MHC). To compare the biochemical and physiological properties of these fibres
      with other skeletal fibre types, we examined the histochemical and
      immunohistochemical staining characteristics, maximum velocity of shortening
      (V(zero)) and MHC isoform content of fibres from rabbit masseter and soleus
      muscles. 2. The fibre-type composition of muscle sections was determined with MHC
      antibodies and myofibrillar ATPase histochemistry. Fibres we designated 'type
      alpha-cardiac' were different from type I and type II fibres in that they stained
      positively with the alpha-cardiac MHC antibody and they maintained. ATPase
      reactivity after acid and alkali pre-incubations. Samples of superficial masseter
      contained a few type I fibres, with the majority of fibres classified as either
      type IIA or type alpha-cardiac. Soleus samples contained type I, IIA and IIC
      fibres. 3. The V(zero) of chemically skinned fibres was determined by the slack
      test method. Each fibre was subsequently characterized as type I, IIA, IIC or
      alpha-cardiac from MHC identification using gel electrophoresis (SDS-PAGE). In
      masseter fibres the V(zero) values were (in muscle lengths s-1): type I, 0.54 +/-
      0.05 (mean +/- S.D., n = 3); type IIA, 1.23 +/- 0.34 (n = 27); type alpha
      cardiac, 0.78 +/- 0.08 (n = 9). In soleus fibres V(zero) values were: type I,
      0.55 +/- 0.06 (n = 14); type IIA, 0.89 +/- 0.04 (n = 8); type IIC, 0.73 (n = 2).
      4. We conclude that the rabbit masseter muscle contains an 'alpha-cardiac' fibre
      type that is distinct from other skeletal fibres. This fibre type expresses only
      the alpha-cardiac MHC, has unusual myofibrillar ATPase reactivity and has a
      V(zero) intermediate between type I and type II fibres.

PMID- 8734978
TI  - Mechanisms of glutamate-stimulated Mg2+ influx and subsequent Mg2+ efflux in rat
      forebrain neurones in culture.
AB  - 1. Mag-fura-2 fluorescence microscopy and whole-cell patch-clamp recordings were
      used to measure glutamate-induced changes in the intracellular free Mg2+
      concentration ([Mg2+]i) and Mg2+ currents, respectively, in cultured forebrain
      neurones from fetal rats in the absence of extracellular Na+ (Nao+) and Ca2+
      (Cao2+). 2. Increasing the extracellular Mg2+ concentration ([Mg2+]o) from 9 to
      70 mM significantly enhanced the maximum [Mg2+]i induced by a 5 min 100 microM
      glutamate plus 1 microM glycine stimulation ([Mg2+]i,5 min) from 2.04 +/- 0.07 to
      2.98 +/- 0.20 mM. Increasing [Mg2+]o from 9 to 70 mM also significantly enhanced
      the initial rate of rise in [Mg2+]i upon glutamate stimulation from 0.41 +/- 0.02
      to 0.81 +/- 0.08 mM min-1. 3. The glutamate-stimulated increase in [Mg2+]i was
      not altered by prior depletion of intracellular free Na+ (Nai+). For paired
      stimulations in single neurones, the mean [Mg2+]i,5 min was 1.95 +/- 0.17 mM
      under Na(+)-depleted conditions and 1.94 +/- 0.16 mM under control conditions. 4.
      The glutamate-stimulated increase in [Mg2+]i was significantly reduced when NMDA
      channel-permeant Cs+ or K+ ions were used as the Na+ substitute instead of the
      presumably NMDA channel-impermeant ions N-methyl-D-glucamine (NMDG), Tris or
      sucrose. The mean [Mg2+]i,5 min was 0.56 +/- 0.06 and 0.74 +/- 0.08 mM in the
      presence of Cs+ or K+, respectively, compared with 2.13 +/- 0.10, 1.93 +/- 0.11
      and 2.07 +/- 0.22 mM in the presence of NMDG, Tris or sucrose, respectively. 5.
      In whole-cell recordings performed with Cs+ as the primary intracellular cation,
      application of 100 microM NMDA plus 10 microM glycine induced inward currents
      that reversed around -55 mV in an extracellular solution containing 70 mM Mg2+
      and 31 mM NMDG as the only cations. The currents were reversibly inhibited by DL
      2-amino-5-phosphonovaleric acid (APV). In an extracellular solution containing 2
      mM Mg2+ and 140 mM NMDG, NMDA plus glycine activated outward currents at
      potentials more depolarized than -90 mV. 6. In whole-cell recordings made with
      NMDG as the principal cation in the patch pipette, application of NMDA plus
      glycine in the 70 mM Mg2+ extracellular solution induced inward currents at
      voltages more negative than +15 mV. The ratio of the current measured under these
      conditions to the current measured in an extracellular solution containing Na+ as
      the principal cation (0.073:1) was nearly constant from cell to cell. 7.
      Following a 5 min glutamate stimulation in the presence of 9 mM Mg2+, [Mg2+]i
      returned to basal levels at a mean rate of 58.1 +/- 2.1 microM min-1. Complete
      removal of Nao+ significantly inhibited the rate of recovery to 31% of control.
      Raising [Mg2+]o to 30 mM in combination with removal of Nao+ did not inhibit
      recovery significantly more than either manipulation alone (28% of control). 8.
      These results suggest that glutamate-stimulated increases in [Mg2+]i that occur
      in the absence of Nao+ and Cao2+ result from Mg2+ entry through NMDA-activated
      ion channels. Furthermore, recovery from a glutamate-induced Mg2+ load appears to
      be primarily due to Mg2+ efflux via a mechanism whose characteristics are
      consistent with Na(+)-Mg2+ exchange.

PMID- 8734980
TI  - Nucleotide binding by actomyosin as a determinant of relaxation kinetics of
      rabbit phasic and tonic smooth muscle.
AB  - 1. The apparent second-order rate constants (k+T) of ATP-induced cross-bridge
      detachment from rigor in the absence of Ca2+ were determined with laser flash
      photolysis of caged ATP (cATP) in alpha-toxin-permeabilized tonic, rabbit femoral
      artery and phasic, rabbit bladder smooth muscles. The potential effect of cATP
      binding to actomyosin (AM) on cross-bridge kinetics was examined by varying the
      initial concentration of cATP 2-fold. For a given [ATP] released from either 10
      or 5 mM cATP, the kinetics of relaxation were not significantly different; the
      estimated dissociation constant for cATP binding to smooth muscle AM was 1-3 mM.
      2. k+T was significantly higher ((9.5 +/- 1.3) x 10(4) M-1 s-1) in the phasic
      than in the tonic ((3.0 +/- 1.0) x 10(4) M-1 s-1) smooth muscle. 3. We conclude
      that the combination of the significantly lower (approximately 3 times) apparent
      second-order rate constant of MgATP association with the approximately 5 times
      higher affinity of cross-bridges for MgADP in tonic, than in phasic, smooth
      muscle is a major determinant of the slower kinetics of relaxation and, probably,
      shortening velocity of tonic smooth muscle.

PMID- 8734981
TI  - Origin of concurrent ATPase activities in skinned cardiac trabeculae from rat.
AB  - 1. To determine the rate of ATP turnover by the sarcoplasmic reticulum (SR) Ca2+
      pump in cardiac muscle, and to assess the contributions of other ATPase
      activities to the overall ATP turnover rate, ATPase activity and isometric force
      production were studied in saponin-skinned trabeculae from rat. ATP hydrolysis
      was enzymatically coupled to the oxidation of NADH; the concentration of NADH was
      monitored photometrically. All measurements were performed at 20 +/- 1 degrees C
      and pH 7.0. Resting sarcomere length was adjusted to 2.1 microns. All solutions
      contained 5 mM caffeine to ensure continuous release of Ca2+ from the SR. 2. The
      Ca(2+)-independent ATPase activity, determined in relaxing solution (pCa 9),
      amounted to 130 +/- 13 microM s-1 (mean +/- S.E.M., n = 7) at the beginning of an
      experiment. During subsequent measurements in relaxing solution, a decrease in
      ATPase activity was observed, indicative of loss of membrane-bound ATPase
      activity. The steady-state Ca(2+)-independent (basal) ATPase activity was 83 +/-
      5 microM s-1 (n = 66). 3. Treatment of saponin-skinned preparations with Triton X
      100 abolished 50 microM s-1 (60%) of the basal ATPase activity. Addition of
      ouabain (1 mM) suppressed 14 +/- 5% of the basal activity, whereas 8 +/- 3% was
      suppressed by 20 microM cyclopiazonic acid (CPA). It is argued that 31 microM s-1
      of the basal ATPase activity may be associated with MgATPase from the transverse
      tubular system. 4. The maximal Ca(2+)-activated ATPase activity, i.e. the total
      ATPase activity (determined in activating solution, pCa 4.3) corrected for basal
      ATPase activity, was found to be 409 +/- 15 microM s-1 (n = 66). Experiments with
      CPA indicated that at least 9 +/- 6% of the maximal Ca(2+)-activated ATPase
      activity originates from the sarcoplasmic Ca2+ pump. These experiments indicate
      that the rate of ATP consumption by the SR Ca2+ transporting ATPase amounts to at
      least 37 microM s-1. 5. Treatment of preparations with Triton X-100 abolished 15
      +/- 3% of the maximal Ca(2+)-activated ATPase activity, indicating that 15 +/- 3%
      of the maximal Ca(2+)-activated ATPase activity is membrane bound. 6. Variation
      of free [Ca2+] indicated that apart from the actomyosin ATPase activity a second
      Ca(2+)-dependent ATPase activity contributed to the overall ATP turnover rate.
      This activity was half-maximal at pCa 6.21, and probably reflects the SR Ca2+
      transporting ATPase. It constituted 18 +/- 3% of the Ca(2+)-dependent ATPase
      activity, yielding an upper limit for the SR Ca2+ transporting ATPase activity of
      74 microM s-1.

PMID- 8734982
TI  - Calcium handling and purinoceptor subtypes involved in ATP-induced contraction in
      rat small mesenteric arteries.
AB  - 1. The relationship between the stimulation of ATP receptors, the increase in
      intracellular free calcium concentration ([Ca2+]i; measured using the fluorescent
      indicator fura-2), contraction and the subtypes of purinoceptors involved were
      investigated in the small mesenteric artery of the rat. 2. In normal
      physiological solution, ATP (0.001-3 mM) caused concentration-dependent increases
      in both [Ca2+]i and contraction. Both responses produced by ATP (1 mM) were
      inhibited by 50% in the presence of nitrendipine (1 microM) and were abolished in
      the presence of nitrendipine plus SK&F 96365 (30 microM). 3. In Ca(2+)-free
      medium, ATP (3 mM) elicited a transient increase in both [Ca2+]i and tension
      which were abolished by caffeine and decreased by 65% by thapsigargin (1 microM).
      Moreover, ATP (1 and 3 mM) produced increases in the [3H]D-myo-inositol 1,4,5
      trisphosphate ([3H]IP3) content of vessels in a concentration-dependent manner.
      4. Treatment of the vessels with Bordetella pertussis toxin (PTX) inhibited
      contractions to ATP linked to the influx of calcium through nitrendipine
      sensitive mechanisms, but not those linked to the release of Ca2+ from
      intracellular stores nor the capacity of ATP in increasing IP3 content of the
      vessels. 5. The order of potency of ATP and its analogues in eliciting
      contraction was alpha, beta-methylene-ATP (alpha, beta-MeATP) > 2-methylthio-ATP
      (2-MeSATP) > ATP = ADP. The response to ATP was inhibited by suramin. Reactive
      Blue 2 (up to 100 microM) did not affect the contractile response to ATP.
      Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid 4-sodium (PPADS) and
      alpha, beta-MeATP abolished the response to low concentrations of ATP and reduced
      contractions elicited by high concentrations of ATP. 6. After blockade of P2X
      purinoceptors with PPADS, the order of potency of ATP and its analogues was 2
      MeSATP > ATP = ADP. UTP produced concentration-dependent contractions which were
      not affected by suramin, Reactive Blue 2, PPADS or alpha, beta-MeATP, suggesting
      the presence of P2U-purinoceptors. 7. The results suggest that low concentrations
      of ATP activate P2X-purinoceptors and produce an influx of calcium through both
      voltage-dependent calcium channels sensitive to nitrendipine and through receptor
      operated calcium channels sensitive to SK&F 96365. High concentrations of ATP
      activate P2Y-purinoceptors which promote firstly a nitrendipine-sensitive calcium
      influx via a PTX-sensitive G protein and secondly a release of Ca2+ from an
      internal source via the production of IP3.

PMID- 8734983
TI  - The effect of muscle length on intracellular calcium and force in single fibres
      from mouse skeletal muscle.
AB  - 1. The effect of muscle length on the myoplasmic free Ca2+ concentration
      ([Ca2+]i) and tetanic force production of intact single muscle fibres was
      investigated in the mouse flexor brevis muscle. Muscle fibres were analysed at
      100 microns intervals from 100 microns shorter than the optimum length (L(zero))
      to 300 microns longer than L(zero). The fluorescent Ca2+ indicator indo-1 was
      used to measure [Ca2+]i. 2. Changes in muscle length did not significantly affect
      tetanic or resting [Ca2+]i. However, at lower stimulus frequencies (30-50 Hz) the
      force-length relation was shifted to longer muscle lengths. 3. Force-tetanic
      [Ca2+]i curves were constructed at each muscle length. A comparison of these
      curves revealed that the Ca2+ sensitivity was length dependent. Ca2+ sensitivity
      increased over the ascending limb and plateau phase of the force-length curve,
      but over the descending limb Ca2+ sensitivity reached a plateau and then started
      to decrease once more. 4. These results show that length-dependent changes in
      Ca2+ sensitivity of single muscle fibres cannot simply be related to variations
      in sarcomere length. It is proposed that other factors, such as cross-bridge
      attachment and/or developed force, have a role in determining the Ca2+
      sensitivity at a particular muscle length.

PMID- 8734984
TI  - Role of calbindin-D9k in buffering cytosolic free Ca2+ ions in pig duodenal
      enterocytes.
AB  - 1. The aim of the present study was to test whether the vitamin D-dependent
      Ca(2+)-binding protein calbindin-D9k could function as an important cytosolic
      Ca2+ buffer in duodenal enterocytes while facilitating transepithelial active
      transport of Ca2+ ions. For the investigations we used dual-wavelength,
      fluorescence ratio imaging, with fura-2 as the Ca(2+)-sensitive dye, to measure
      changes in cytosolic concentrations of free Ca2+ ions ([Ca2+]i) in isolated pig
      duodenal enterocytes affected by different cytosolic calbindin-D9k
      concentrations. 2. Epithelial cells were obtained from weaned piglets with normal
      calbindin-D9k concentrations (con-piglets), from piglets with low calbindin-D9k
      levels due to inherited calcitriol deficiency caused by defective renal 25
      hydroxycholecalciferol D3-1 alpha-hydroxylase activity (def-piglets), and from
      piglets with reconstituted calbindin-D9k concentrations, i.e. def-animals treated
      with high doses of vitamin D3 which elevated plasma calcitriol levels by
      extrarenal production (def-D3-piglets). Basal levels of [Ca2+]i ranged between
      170 and 205 nM and did not differ significantly between the groups. 3. After
      addition of 5 mM theophylline, the [Ca2+]i in enterocytes from con-piglets
      doubled during the 10 min incubation. This effect, however, was three times
      higher in enterocytes from def-piglets compared with those from con-piglets.
      Similar results were obtained after 4 min incubation of enterocytes from con- and
      def-piglets in the presence of 1 microM ionomycin. In preparations from def-D3
      piglets, ionomycin-induced increases in [Ca2+]i were significantly lower compared
      with enterocytes from def-piglets and were not different from the control values.
      4. From the results, substantial support is given for the hypothesis that one of
      the major functions of mucosal calbindin-D9k is the effective buffering of Ca2+
      ions.

PMID- 8734985
TI  - Slowing of relaxation and [Ca2+]i during prolonged tetanic stimulation of single
      fibres from Xenopus skeletal muscle.
AB  - 1. Parvalbumin (PA) has been proposed to take up Ca2+ and enhance skeletal muscle
      relaxation in brief contractions; as the duration of the contraction is
      increased, PA will become saturated with Ca2+ and no longer contribute to
      relaxation which therefore will be slowed. The rate of Ca2+ loading of PA is
      determined by the Mg2+ off rate (about 4 s-1 at 22 degrees C). In the present
      study we produced prolonged tetani in intact, single fibres of Xenopus frogs
      while measuring force and the free myoplasmic [Ca2+] ([Ca2+]i) with indo-1. 2.
      Mean rate constants of slowing of force relaxation with increasing tetanus
      duration ranged between 3.2 and 4.8 s-1, thus, similar to the Mg2+ off rate of
      PA. 3. The amplitude of the tail of [Ca2+]i after tetani increased with tetanus
      duration. This increase developed with a rate constant similar to the Mg2+ off
      rate of PA 4. Steady-state force-[Ca2+]i curves were produced from tetani of
      various frequencies and tetani produced when force was depressed after fatiguing
      stimulation. These curves were used to convert [Ca2+]i records into Ca(2+)
      derived force. Relaxation of Ca(2+)-derived force was slowed following a time
      course similar to that of real force. The lag between Ca(2+)-derived and real
      force during relaxation was not affected by tetanus duration. 5. Tails of
      elevated [Ca2+]i after tetani were used to analyse the function of the SR Ca2+
      pumps. This analysis showed a marked decline in the rate of Ca2+ uptake with
      prolonged tetani. 6. In conclusion, in Xenopus fibres the slowing of relaxation
      with increasing tetanus duration can be explained by altered Ca2+ handling due to
      PA Ca2+ loading and impaired SR Ca2+ uptake. This contrasts to our previous
      results in mouse fibres and the difference can be explained by a markedly lower
      rate of SR Ca2+ uptake resulting in higher tetanic [Ca2+]i in Xenopus fibres.

PMID- 8734986
TI  - Albumin stimulates uptake of calcium into subcellular stores in rat cortical
      astrocytes.
AB  - 1. When albumin from either plasma or serum is applied at low concentrations to
      cortical astrocytes a decrease in the level of [Ca2+]i is observed. At higher
      concentrations trains of calcium spikes are seen. 2. Removal of the polar lipids
      which are normally bound to native albumin abolishes the ability to induce
      spikes, but the decrease in [Ca2+]i is unaffected. The decrease is abolished by
      the denaturation of albumin and is not reproduced by a number of other proteins,
      and is therefore a specific action of albumin. We conclude that native albumin
      has a dual agonist action: the decrease in [Ca2+]i is induced by the albumin
      protein molecule, while the spikes are induced by a lipid normally bound to it.
      3. The decrease is rapid (fastest tau = 12 s) and the rate is dependent on the
      concentration of albumin. [Ca2+]i falls from 77 nM to around 34 nM in the
      presence of saturating levels of albumin, and this level appears to be maintained
      indefinitely. 4. The decrease is due to an uptake of calcium into subcellular
      stores, as it is not abolished by removal of external Ca2+ or Na+ but is
      abolished by thapsigargin and cyclopiazonic acid, which are specific inhibitors
      of the endoplasmic reticulum Ca(2+)-ATPase. 5. When the state of store filling
      after albumin application is probed with a pulse of glutamate it can be seen that
      stores fill with the same time course as the decrease in [Ca2+]i. The low level
      of [Ca2+]i in albumin must therefore be maintained by a suppression of calcium
      influx rather than by a continued uptake into stores. 6. The calcium uptake
      potentiates the efficacy of low concentrations of calcium-releasing agonists such
      as glutamate and bradykinin by almost an order of magnitude. 7. A possible
      function for the calcium uptake caused by albumin is to potentiate the production
      of calcium spike trains by promoting refilling of calcium stores in the intervals
      between spikes. The uptake may play a role in the response of astrocytes to
      damage in the CNS.

PMID- 8734987
TI  - P2U receptor is linked to cytosolic Ca2+ transient and release of vasorelaxing
      factor in bovine endothelial cells in situ.
AB  - 1. With the use of front-surface fluorimetry and fura-2-loaded strips of bovine
      aortic valve, we characterized the [Ca2+]i transients induced in endothelial
      cells in situ using a non-selective purinergic agonist (adenosine 5'-triphosphate
      (ATP)), and selective agonists for P2X (alpha, beta-methylene ATP), P2Y (2
      methylthio-ATP (2MeSATP)) and P2U (uridine 5'-triphosphate (UTP)) purinoceptors
      and an unrelated agonist bradykinin (BK). 2. Double staining with fura-2 and
      acetylated low-density lipoprotein labelled with 1,1'-dioctadecyl-3,3,3',3'
      tetramethyl-indo-carbocyanine perchlorate showed that the fura-2 fluorescence
      arose exclusively from a single monolayer of endothelial cells covering the
      surface of the valvular strips. 3. All nucleotides (ATP, UTP and 2MeSATP) induced
      an elevation of the intracellular Ca2+ concentration ([Ca2+]i), with an initial
      transient peak and a subsequent lower sustained elevation. Blockade of the Ca2+
      influx with 1 mM Ni2+ did not affect the peak levels of the [Ca2+]i transients,
      whereas it abolished the sustained increases in [Ca2+]i induced by these
      nucleotides. 4. The potency order of these nucleotides was 2MeSATP > ATP > UTP,
      while the order of the maximum responses was UTP = ATP > 2MeSATP. alpha, beta
      Methylene ATP (up to 1 mM) had only a minimal effect. 5. Prolonged exposure to
      ATP or UTP, at concentrations giving a maximum response, desensitized the
      responses to ATP, UTP and 2MeSATP, but not to BK. Prolonged exposure to 2MeSATP
      at concentrations giving a maximum response did not desensitize the responses to
      UTP or BK, but did desensitize those to ATP and 2MeSATP. Prolonged exposure to BK
      did not induce heterologous desensitization to any of the three nucleotides. 6.
      [Ca2+]i elevation in valvular endothelial cells induced by UTP was associated
      with the relaxation of adjacent vascular medial strips precontracted with U
      46619, the stable analogue of thromboxane A2. 7. We conclude that: (1) the peak
      elevation of the [Ca2+]i transient induced by these nucleotides is independent of
      extracellular Ca2+, which therefore suggests the release of intracellular Ca2+
      and, (2) mature endothelial cells in situ, in a valvular preparation, have a
      common receptor for ATP and UTP (nucleotide or P2U receptor), which coexists with
      the P2Y receptor. Thus we propose that the activation of the nucleotide receptor,
      P2U, induces [Ca2+]i elevation in endothelial cells in situ, and thus leads to
      the release of vasorelaxing factors.

PMID- 8734988
TI  - Ca2+ current expression in pituitary melanotrophs of neonatal rats and its
      regulation by D2 dopamine receptors.
AB  - 1. We have examined the voltage-dependent Ca2+ channel activity of rat
      melanotrophs during the early postnatal period. The cells were dissociated from
      pituitary intermediate lobes, kept in culture for 5-24 h and then subjected to
      whole-cell patch-clamp experiments. 2. Like their adult counterparts, neonatal
      melanotrophs were able to generate Na+ currents, K+ currents and Ca2+ currents in
      response to membrane depolarization. Ca2+ currents were carried by both low- and
      high-threshold Ca2+ channels. 3. High-threshold Ca2+ current density decreased
      sharply between postnatal day 4 (P4) and P12. This period coincides with the
      onset of dopaminergic innervation within the intermediate lobe. Accordingly, the
      developmental decrease in Ca2+ current density was largely reversed by chronic in
      vivo treatment with sulpiride, a dopamine D2 receptor antagonist. 4. Prolonging
      the time in culture from 5 h to 8 days did not significantly alter the Ca2+
      channel activity of P3 melanotrophs, whereas the high-threshold Ca2+ current in
      previously innervated (P14) melanotrophs stayed small for the first 24 h and then
      increased 3-fold during the subsequent 4-5 days. This increase required RNA and
      protein synthesis and was prevented by adding D2 agonists to the culture medium.
      5. These results provide evidence for a postnatal suppression of high-threshold
      Ca2+ current expression in pituitary melanotrophs mediated by presynaptic
      dopamine neurons through D2 dopamine receptors.

PMID- 8734989
TI  - Structural determinants of channel conductance in fetal and adult rat muscle
      acetylcholine receptors.
AB  - 1. The structural basis of the developmentally regulated increase in endplate
      channel conductance in rat, where the gamma-subunit of the fetal muscle
      acetylcholine receptor (gamma-AChR) is replaced by the epsilon-subunit in the
      adult muscle receptor (epsilon-AChR), was investigated by analysing the structure
      of gamma- and epsilon-subunit genes and by expressing recombinant AChR channels
      of different molecular composition in Xenopus oocytes and measuring their single
      channel conductance. 2. The gamma- and epsilon-subunit genes each have twelve
      exons. In both subunits, the four homologous segments, designated M1, M2, M3 and
      M4, which are thought to contribute to the formation of the pore, are encoded by
      four separate exons, E7, E8, E9 and E12. 3. Chimaeric epsilon(gamma)- or
      gamma(epsilon)-subunits were constructed from the parental epsilon- and gamma
      subunits, respectively. Exchanging the four hydrophobic segments (M1-M4) of the
      gamma-subunit for those of the epsilon-subunit and vice versa completely reversed
      the difference in conductance between gamma-AChR and epsilon-AChR channels. 4.
      Effects of single- and multiple-point mutations in M1-M4 segments of gamma- and
      epsilon-subunits indicate that the major determinants of the difference in
      conductance between fetal and adult endplate channels are located in the M2
      segment. The key differences are the exchange of alanine/threonine (gamma
      subunit) for serine/isoleucine (epsilon-subunit) in M2, and the lysine (gamma
      subunit) for glutamine (epsilon-subunit) exchanges in the regions flanking the M2
      segment.

PMID- 8734990
TI  - Regional differences in the negative inotropic effect of acetylcholine within the
      canine ventricle.
AB  - 1. Regional differences in the effects of ACh on sub-epicardial, mid-wall and sub
      endocardial cells of the dog left ventricle have been studied. 2. ACh produced a
      dose-dependent, atropine-sensitive negative inotropic effect that was greatest in
      sub-epicardial cells and small or absent in sub-endocardial cells. 3. In sub
      epicardial (but not sub-endocardial) cells, ACh also resulted in a dose-dependent
      decrease in action potential duration. The inotropic effect of ACh on sub
      epicardial cells was primarily the result of the decrease of action potential
      duration, because during trains of voltage clamp pulses the inotropic effect of
      ACh was reduced or abolished. At a holding potential of -80 mV, 10(-5)M ACh
      decreased L-type Ca2+ current by approximately 8% and this is thought to be
      responsible for the small inotropic effect during trains of pulses. 4. Although 4
      AP, a blocker of the transient outward current (I(to)), abolished the "spike and
      dome' morphology of the sub-epicardial action potential, it had little or no
      effect on the actions of ACh on sub-epicardial cells. ACh had no effect on I(to)
      in sub-epicardial cells in voltage clamp experiments. 5. ACh activated a Ba(2+)
      sensitive outward current (IK,ACh) in sub-epicardial cells, but little or no such
      current in sub-endocardial cells. In sub-epicardial cells, ACh also inhibited the
      inward rectifier current, IK,1. 6. It is concluded that in left ventricular sub
      epicardial cells, ACh activates IK,ACh. This results in a shortening of the
      action potential and, therefore, a negative inotropic effect. In subendocardial
      cells, ACh activates little or no IK,ACh and, therefore, it has little or no
      negative inotropic effect. This may result from a regional variation in the
      expression of the muscarinic K+ channel.

PMID- 8734991
TI  - Selective activation of exocytosis by low concentrations of ACh in rat pancreatic
      acinar cells.
AB  - 1. We have monitored changes in membrane capacitance (delta C) and conductance
      (delta G) induced by muscarinic acetylcholine stimulation in single rat
      pancreatic acinar cells. 2. Acetylcholine (ACh, 500 nM) induced simultaneous
      increases of delta C and delta G. In contrast, a low concentration (50 nM) of ACh
      exclusively induced delta C increases without delta G. These responses were
      abolished by the internal perfusion of heparin. This indicates that inositol
      1,4,5-trisphosphate-mediated internal Ca2+ mobilization either simultaneously
      activates exocytosis and ion channels or exclusively initiates exocytosis. In
      comparison, a low concentration of A23187 selectively activated ion channels but
      a high concentration activated exocytosis and ion channels simultaneously. 3.
      These selective response patterns of delta C and delta G depend on the choice of
      agonist and the internal EGTA concentration. From this, we postulated two
      explanations for the selective action of muscarinic ACh stimulation on
      exocytosis. First, an area of high [Ca2+]i, spatially close to secretory
      granules, activates exocytosis. Second, an as yet unknown signalling factor
      sensitizes the Ca2+ affinity of the exocytotic apparatus.

PMID- 8734992
TI  - Synchronous release of ATP and neurotransmitter within milliseconds of a motor
      nerve impulse in the frog.
AB  - 1. It has been suggested that ATP is released together with the neurotransmitter
      acetylcholine (ACh) and, after hydrolysis to adenosine, is the primary
      physiological mediator of prejunctional neuromuscular depression. To evaluate
      whether ATP is released with sufficient rapidity to mediate prejunctional
      depression, outside-out patches containing both ATP-gated and ACh-gated ion
      channels were made from acutely dissociated guinea-pig sympathetic neurons and
      used to detect the co-release of nucleotide and neurotransmitter in frog
      cutaneous pectoris nerve-muscle preparations. 2. In a normal bathing solution in
      which muscle nicotinic receptors were blocked, a single stimulus to the motor
      nerve produced channel openings in the detector patch characteristic of both ATP
      and ACh. 3. In the remaining experiments, preparations were treated with
      sufficient hexamethonium (200 microM) to block nicotinic responses in the
      detector patch. In these experiments, a single temporally isolated nerve impulse
      caused the synchronous opening of ATP-gated channels in the detector patch with a
      latency of < 5 ms when patches were placed within 10 microns of the motor nerve
      ending. This multichannel phasic response was followed by trail of discrete
      channel openings characteristic of ATP-gated channels. 4. The selective ATP
      antagonist suramin (50 microM) reversibly eliminated the response to nerve
      stimulation. 5. The results suggest that ATP is released synchronously together
      with the neurotransmitter ACh in response to an individual nerve impulse and with
      a brief latency characteristic of quantal release from synaptic vesicles.

PMID- 8734993
TI  - Volatile anaesthetic enhancement of paired-pulse depression investigated in the
      rat hippocampus in vitro.
AB  - 1. A prominent in vivo effect of general anaesthetics, including volatile
      anaesthetics such as halothane, is the prolonging of paired-pulse depression of
      the hippocampal CA1 population spike. The mechanisms by which volatile
      anaesthetics produce this effect were investigated in the hippocampal brain slice
      preparation by testing the effect of halothane on several long-lasting inhibitory
      processes, including the calcium-activated potassium current that underlies the
      slow after-hyperpolarization (IAHP), the GABAB-mediated potassium current that
      underlies the late IPSP, and the fast and slow components of the early GABAA
      mediated IPSP. 2. Halothane produced a dose-dependent block of IAHP at
      concentrations between 0.5 and 1.5%. This block was manifested as a reduction in
      spike frequency adaptation, a reduction in the amplitude of the slow after
      hyperpolarization following a train of action potentials, and a reduction in the
      amplitude of the voltage-clamped current following a calcium spike elicited in
      the presence of tetraethylammonium and tetrodotoxin. The effect did not appear to
      be caused by blockade of voltage-sensitive calcium channels, since halothane
      markedly reduced IAHP at a concentration (1.5%) that had little effect on the
      depolarization-evoked calcium spike. 3. Halothane reduced the amplitude of the
      late GABAB-mediated IPSP by approximately 50% at concentrations between 1 and 2%.
      Similar results were obtained for polysynaptic and monosynaptic responses, and
      with current-clamp and voltage-clamp recordings. However, halothane, at
      concentrations up to 3%, had no effect on the presynaptic GABAB response, as
      indicated by no reduction in paired-pulse depression of the monosynaptic GABAA
      response. 4. Halothane (2%) and enflurane (4%) prolonged the decay phase of the
      slow component of the monosynaptic GABAA-mediated IPSC approximately twofold, but
      did not alter the amplitude of the response. Halothane also prolonged the decay
      phase of the fast component of the GABAA-mediated IPSC, with no effect on the
      amplitude. However, enflurane markedly reduced the amplitude of the fast
      component of the GABAA IPSC, so that only a small slow current remained in
      response to a selective stimulus. 5. It is concluded that the effects of
      halothane on IAHP and on GABAB responses cannot account for its effects on paired
      pulse depression, but that volatile anaesthetics enhance paired-pulse depression
      by prolonging the decay of the slow dendritic GABAA response. Furthermore, it is
      speculated that the proconvulsant property of enflurane is related to its
      depression of the fast somatic component of GABAA inhibition.

PMID- 8734994
TI  - Ischaemia-sensitive sympathetic afferents innervating the gastrointestinal tract
      function as nociceptors in cats.
AB  - 1. Activation of sympathetic visceral afferents during mesenteric ischaemia
      induces visceral pain and reflexly excites the cardiovascular system. The present
      study investigated the differential responses of ischaemically sensitive and
      insensitive sympathetic C fibre afferents to graded distension of the
      gastrointestinal tract. 2. Single-unit activity of C fibre afferents innervating
      the stomach, duodenum and jejunum was recorded from the right thoracic
      sympathetic chain of anaesthetized cats. Ischaemically sensitive and insensitive
      C fibre afferents were identified according to their response to 5-20 min of
      ischaemia. The functional characteristics of the stimulus-response relationships
      of afferents were determined by distension of a balloon placed in the
      corresponding segment of gastrointestinal tract. 3. The results show that
      ischaemically insensitive C fibre afferents had a lower threshold in response to
      distension (13 +/- 5 mmHg, n = 10). The discharge frequency of these afferents
      was saturated within a low pressure range of distension. However, ischaemically
      sensitive C fibre afferents had a high threshold (86 +/- 12 mmHg, n = 10) and a
      larger peak response to mechanical distension in the noxious range (60-180 mmHg).
      There were no differences between ischaemically sensitive and insensitive C fibre
      afferents with regard to their testing activity or responses to bradykinin (10
      micrograms I.A.). 4. This study demonstrates that the gastrointestinal system is
      innervated by low and high threshold sympathetic C fibre afferents, the latter
      having the distinct ability to encode nociceptive information such as excessive
      distension and ischaemia.

PMID- 8734995
TI  - Specific thermal responsiveness of ventromedial hypothalamic neurons to localized
      scrotal heating and cooling in rats.
AB  - 1. The specificity of thermoresponsive ventromedial hypothalamic (VMH) neurons to
      localized, incremental scrotal thermal cooling and heating of urethane
      anaesthetized male Sprague-Dawley rats (maintained at 37 degrees C colonically)
      was investigated. 2. Ventromedial hypothalamic extracellular neuronal activity
      and surface (scalp) electroencephalogram (EEG) activity from the parietal region
      were recorded. Intrascapular brown adipose tissue (TIBAT), surface tail (Tt) and
      scrotal (Tsc) temperatures, where thermal stimulation was evoked, were also
      monitored. 3. One hundred and twenty-five VMH neurons were recorded, with forty
      (32%) VMH neurons classified as warm-responsive neurons (WRNs), twenty-three
      (18%) as coldresponsive neurons (CRNs) and sixty-two (50%) as thermal non
      responsive neurons (TNRNs) based on their thermal coefficients. Of VMH WRNs, 60%
      (i.e. 24) were classified as having biphasic neuronal activity responses, as were
      60% (i.e. 14 of 23) of the CRNs. Forty per cent of WRNs and CRNs were classified
      as having monophasic changes in neuronal activity. 4. Scrotal heating or cooling
      from 5 to 40 degrees C resulted in specific firing rate changes of VMH WRNs and
      CRNs without any associated change in EEG activity (i.e. no significant change in
      EEG frequency or amplitude from initial baseline EEG activity when Tsc was 20
      degrees C). EEG desynchronization (increased EEG frequency, decreased amplitude)
      was only observed when scrotal temperatures were at 45 degrees C or after each
      tail pinch (noxious stimulation) but not with scrotal brushing (mechanical
      stimulation). 5. With core temperature maintained at 37 degrees C, localized,
      scrotal heating and cooling of rats did not induce IBAT temperature changes
      indicative of brown adipose tissue activation, but delayed changes in tail
      temperature, indicative of vasoactive effector responses, did occur.

PMID- 8734996
TI  - Long-lasting synaptic facilitation induced by serotonin in superficial dorsal
      horn neurones of the rat spinal cord.
AB  - 1. Modulatory actions of serotonin (5-hydroxytryptamine, 5-HT) on excitatory
      postsynaptic currents (EPSCs) were studied with whole-cell recordings from
      superficial dorsal horn (SDH) neurones in neonatal rat spinal cord slices. In one
      third of SDH neurones, 5-HT induced a sustained potentiation of evoked EPSCs
      lasting for more than 30 min after wash-out. This potentiation was often preceded
      by a transient suppression of EPSCs. 2. Serotonin differentially modulated the
      frequency of miniature EPSCs recorded in the presence of tetrodotoxin (TTX)
      according to the SDH neurones, producing a transient suppression, a transient
      facilitation or a long-lasting facilitation. 3. The 5-HT1A-receptor agonist 8
      hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) suppressed the amplitude of
      evoked EPSCs and frequency of miniature EPSCs in a reversible manner. In
      contrast, the 5-HT2-receptor agonists 1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane (DOI) and alpha-methyl-5-HT induced long-lasting potentiations of
      EPSC amplitude and miniature EPSC frequency. 4. Neither the mean amplitude nor
      the kinetics of miniature EPSCs were affected by 5-HT during the sustained
      facilitation of miniature EPSC frequency, suggesting that the facilitatory effect
      of 5-HT was presynaptically mediated. The 5-HT-induced long-lasting facilitation
      of miniature EPSC frequency was observed also in Ca(2+)-free, Mg2+ solution. 5.
      The long-lasting facilitation of evoked EPSC amplitude and miniature EPSC
      frequency by 5-HT was mimicked by the phorbol ester, phorbol 12,13-dibutyrate
      (PDBu), and blocked reversibly by the protein kinase C (PKC) inhibitor,
      calphostin C. Forskolin applied together with 3-isobutyl-1-methylxanthine (IBMX)
      had no effect on the evoked EPSCs. 6. We conclude that serotonin can induce a
      long-lasting facilitation of evoked EPSCs and spontaneous release of excitatory
      transmitter at SDH synapses of rat spinal cord. Our results suggest that
      intracellular PKC linked to the 5-HT2 receptor may mediate this effect by
      directly activating the exocytotic machinery.

PMID- 8734998
TI  - Water compartmentalization and extracellular tortuosity after osmotic changes in
      cerebellum of Trachemys scripta.
AB  - 1. Water compartmentalization in the turtle cerebellum subject to media of
      different osmolalities was quantified by combining extracellular diffusion
      analysis with wet weight and dry weight measurements. The diffusion analysis also
      determined the tortuosity of the extracellular space. 2. Isolated cerebella were
      immersed in normal, oxygenated physiological saline (302 mosmol kg-1), hypotonic
      saline (238 mosmol kg-1) and a series of hypertonic salines (up to 668 mosmol kg
      1). The osmolality was varied by altering the NaCl content. 3. Extracellular
      volume fraction and tortuosity of the granular layer of the cerebellum were
      determined from measurements of ionophoretically induced diffusion profiles of
      tetramethylammonium, using ion-selective microelectrodes. The volume fraction was
      0.22 in normal saline, 0.12 in hypotonic medium and 0.60 in the most hypertonic
      medium. Tortuosity was 1.70 in the normal saline, 1.79 in the hypotonic and 1.50
      in the most hypertonic saline. 4. The water content, defined as (wet weight-dry
      weight)/wet weight, of a typical isolated cerebellum (including granular,
      Purkinje cell and molecular layers) was 82.9%. It increased to 85.2% in hypotonic
      saline and decreased to 80.1% in the most hypertonic saline. 5. Measurements of
      extracellular volume fraction and water content were combined to show that
      hypotonic solutions caused water to move from the extracellular to the
      intracellular compartment while hypertonic solutions caused water to move from
      the intracellular to extracellular compartment, with only a relatively small
      changes in total water in both cases. 6. These results suggest the use of the
      isolated turtle cerebellum as a model system for studying light scattering or
      diffusion-weighted magnetic resonance imaging.

PMID- 8734997
TI  - Responses of glutamine transport in cultured rat skeletal muscle to osmotically
      induced changes in cell volume.
AB  - 1. In order to investigate the relationship between cellular hydration state and
      the rate of glutamine transport, tracer glutamine uptake into primary rat
      myotubes was studied at external osmolalities of 170, 320 or 430 mosmol kg-1. 2.
      Incubation of myotubes with glutamine (2 mM; 30 min) at 320 mosmol kg-1 increased
      cell volume and glutamine transport (by 35 and 36%, respectively); insulin (66
      nM; 30 min) also increased cell volume and glutamine transport (by 22 and 40%,
      respectively) and the effects of insulin and glutamine combined were additive.
      The increase in glutamine uptake following glutamine pre-incubation represented
      an increase in Vmax of Na(+)-dependent glutamine transport. 3. There was an
      inverse relationship between myotube glutamine transport and external osmolality
      after 30 min exposure. 4. During hyposmotic (170 mosmol kg-1) exposure there were
      large, rapid increases of cell volume and glutamine transport; the latter
      increased transiently (during the cell swelling phase) by a maximum of
      approximately 80% at 2 min, (due to an increased Vmax for Na(+)-dependent
      glutamine transport) then decayed to a new elevated steady state after 30 min
      exposure. 5. During hyperosmotic (430 mosmol kg-1) exposure there were rapid
      decreases in glutamine transport and myotube cell volume (both by approximately
      30%) to values which were maintained for at least 15 min. 6. The volume-sensitive
      glutamine transport process features characteristics of the insulin-sensitive
      system Nm transporter. 7. Modulation of Na(+)-dependent glutamine transport by
      insulin and cell volume changes may contribute towards regulation of muscle
      metabolism.

PMID- 8734999
TI  - Chronic volume expansion in the rat: proximal tubular Na+ transport and Na+ pump
      inhibition.
AB  - 1. The lesser natriuresis of chronic volume expansion (ChVE) compared with that
      of acute volume expansion (AcVE) implies different homeostatic mechanisms.
      Because little information is available in the literature on proximal tubular
      (PT) Na+ transport and intracellular electrolyte concentrations, these were
      investigated in a rat model of ChVE. 2. Haematocrit was significantly lower and
      urine volume and Na+ excretion were significantly higher in ChVE rats compared
      with control rats. 3. Proximal tubular Na+ transport with artificial PT fluid was
      normal (3.67 +/- 0.09 x 10(-4) mm3 mm-2 s-1; mean+/-S.E.M.), while with
      endogenously harvested tubular fluid it was reduced to 2.78 +/- 0.07 x 10(-4) mm3
      mm-2 s-1 in ChVE rats (P < 0.0001). 4. Intracellular Na+ was significantly
      elevated from 18.0 +/- 0.7 mmol (kg wet wt)-1 in control rats to 20.2 +/- 0.8
      mmol (kg wet wt)-1 in ChVE rats (P = 0.044). The cells showed residual swelling,
      with dry weight and phosphorus values decreasing significantly compared with
      controls (19.5 +/- 0.4 to 18.5 +/- 0.03% and 130.4 +/- 3.7 to 117.8 +/- 2.8 mmol
      (kg wet wt)-1, P = 0.04 and 0.006, respectively). 5. The results demonstrate that
      in ChVE a tubular factor inhibits PT Na+ transport associated with an inhibition
      of the Na+ pump and this resembles one mechanism defined in AcVE.

PMID- 8735001
TI  - Functional development of the sheep diaphragmatic ligament.
AB  - 1. The diaphragmatic ligament, which lines the thoracic surface of the diaphragm,
      plays a major role in setting the passive compliance of the diaphragm in the
      adult. Since many elastic tissues are more compliant at younger ages, our aim was
      to determine whether this diaphragmatic ligament plays an important role during
      development of the diaphragm. 2. We examined the passive biaxial length-tension
      properties of the isolated mid-costal diaphragm from fetal, newborn and adult
      sheep; initially with the diaphragm intact and then with the diaphragmatic
      ligament removed to reveal its functional significance. 3. We found that unlike
      other elastic tissues the diaphragmatic ligament is stiffer in early development
      than in the adult. The diaphragmatic ligament supports about 75% of the passive
      tension in the diaphragm in the 121 day fetus (term at 147 days) declining to
      about 50% from 3 weeks of age. The fetal diaphragm muscle fibres are exposed to 1
      7 kPa of stress over the last 26 days of gestation. 4. We suggest that the
      diaphragmatic ligament provides a structural framework on which the muscle fibres
      of the diaphragm grow in fetal life, and that the ligament's elasticity is
      regulated to maintain a low and constant stress on the diaphragm muscle fibres
      during development.

PMID- 8735000
TI  - Effect of lung liquid volume on respiratory performance after caesarean delivery
      in the lamb.
AB  - 1. The volume of liquid in the lungs of the fetal lamb is reported to fall in the
      final days of gestation and during labour itself. We aimed to test the hypothesis
      that this fall in liquid volume adapts the lungs for air breathing and pulmonary
      gas exchange. 2. In twelve chronically catheterized fetal lambs we measured lung
      liquid volume at 140 days gestation (term is 147 days) and then delivered the
      fetuses by Caesarean section under maternal spinal anaesthesia. In five fetuses
      we removed approximately half the liquid contained in the lungs just before
      delivery (experimental group) while the remaining seven fetuses were delivered
      without change to their lung liquid (control group). 3. Lambs born with reduced
      lung liquid volume improved their arterial blood gas and acid-base status more
      quickly than lambs born without alteration to lung liquid. 4. Carotid arterial
      blood gas values in the first 60 min of postnatal life were significantly related
      to the volume of liquid present in the lungs at birth, with higher arterial
      partial pressure of oxygen (Pa,02) and arterial oxygen saturation (Sa,02) and
      lower arterial partial pressure of carbon dioxide (Pa,CO2) levels being
      associated with lower lung liquid volumes. 5. We conclude that postnatal gas
      exchange is enhanced by a reduction in the volume of liquid remaining in the
      lungs when breathing starts.

PMID- 8735002
TI  - Fusimotor and skeletomotor activities are increased with precision finger
      movement in man.
AB  - 1. Impulses of eighteen muscle spindle afferents from finger extensor muscles
      were recorded from the radial nerve while subjects performed single joint finger
      movements of two kinds, i.e. routine and precision, which were nearly identical
      with regard to kinematics. 2. The firing rates of ten primary and two secondary
      spindle afferents were higher in the precision movements by more than 10%,
      although the difference reached statistical significance in only seven of them.
      In most cases when spindle firing was higher in precision movements the
      skeletomotor activity was higher as well. 3. The findings indicated that the
      fusimotor activity was often stronger with precision movements compared with
      routine movements. This result is in qualitative agreement with several studies
      on behaving cats, demonstrating higher fusimotor activity in more demanding motor
      tasks. On the other hand, the effects were much smaller in humans than in cats.
      Moreover, in contrast to findings from experiments in cats, no support was
      obtained for the hypothesis that fusimotor activity was adjusted independently of
      the skeletomotor activity in human finger muscles.

PMID- 8735004
TI  - From physiology to clinics--20 years of experience with pulsatile GnRH.
AB  - The physiological and the pathophysiological basis of unvariant pulsatile
      administration of gonadotrophin-releasing hormone (GnRH) as well as the clinical
      results are reviewed. Pulsatile administration of GnRH not only proved to be a
      very effective treatment mode but also became an important tool for research in
      the central control of pituitary and ovarian function under normal and disease
      conditions.

PMID- 8735003
TI  - Central motor command activates sympathetic outflow to the cutaneous circulation
      in humans.
AB  - 1. The aim of this study was to provide direct evidence that sympathetic outflow
      to the skin in humans is governed by central neural mechanisms. 2.
      Microneurographic measurements of skin sympathetic nerve activity (SNA) from the
      personal nerve was performed in nine subjects during: (1) static hand grip at 10,
      20 and 30% maximal voluntary contraction (MVC); and (2) attempted static hand
      grip during partial neuromuscular blockade produced by injection of vecuronium.
      3. Two minutes of static hand grip at 20 and 30% MVC (force output, 9.6 +/- 0.2
      and 14.4 +/- 0.3 kg, respectively) evoked significant increase in skin SNA that
      were graded to the intensity of the exercise. Static hand grip at 10% MVC (force
      output, 4.8 +/- 0.1 kg) caused a small but insignificant increase in skin SNA. 4.
      During vecuronium-induced neuromuscular blockade, subjects failed to maintain a
      force output equivalent to the output produced during 10% MVC before vecuronium
      (force output: 1st min, 4.4 +/- 0.6 kg; 2nd min, 2.1 +/- 0.4 kg), in spite of
      maximal effort being applied. This attempted hand grip exercise consistently
      evoked considerable increase in skin SNA that did not significantly differ from
      the responses produced by hand grip at 30% MVC; total skin SNA increased by 246
      +/- 93% during 2 min of attempted hand grip and increased by 243 +/- 77% during 2
      min of static hand grip at 30% MVC (means +/- S.E.M., P < or = 0.05). These
      increase in skin SNA were not due to activation of resting muscles because
      measurements of surface electromyography showed no activity in resting forearm
      muscles during static or attempted hand grip exercise. 5. This study provides
      direct neurophysiological evidence that central motor command can activate
      sympathetic outflow. During static hand grip, central motor command is the
      primary mechanism that stimulates sympathetic outflow to skin.

PMID- 8735005
TI  - The role of the GnRH dose and the route of administration on treatment outcome
      and complications.
AB  - A literature review is given on the pulsedose, the pulse interval, the route of
      administration and the complications of pulsatile GnRH therapy in
      hypogonadotropic patients. It is concluded that the treatment regimen should be
      as follows: 1. Start first treatment cycle with a pulsedose of 5 micrograms/pulse
      and a pulse interval of 120 min. 2. Regardless the outcome of the first treatment
      cycle, during the second cycle either the dose should be increased to 10
      micrograms/pulse or the interval should be reduced to 60 min. 3. Only if
      insufficient results are obtained with this pulsedose should the dose be
      increased to a maximum of 20 micrograms/pulse. With respect to the route of
      administration it is concluded that the choice of the i.v. versus the s.c. route
      of administration is mainly one of personal preference. Complications are mainly
      local inflammatory reactions. All other side effects and complications are rare
      and of minor importance.

PMID- 8735006
TI  - Multiple pregnancies: the price to pay.
AB  - Since 1980, the rate of multiple pregnancies due to assisted reproductive
      technology has been multiplied by 10, especially for twin pregnancies and for
      cases involving simple stimulation of ovulation. The prices paid are: an increase
      in prematurity (82% of deliveries); perinatal mortality (an increase of 74%); and
      transfer to intensive care units (95% of infants born of multiple pregnancies).
      This does not take into account the rise in cost per child, which increased by
      1.9 for twins and 3.7 for triplets. The solution does not lie in selective embryo
      reduction but in the reduction of the number of embryos transferred.

PMID- 8735007
TI  - Is multiple pregnancy an unavoidable complication of ovulation induction? The
      case for pulsatile GnRH.
AB  - Ovarian hyperstimulation (OHS) and multiple pregnancy are dreaded complications
      of ovulation induction. The use of pulsatile GnRH permits to prevent the
      occurrence of OHS and results in few multiple pregnancies. Low-dose GnRH
      administration, avoidance of preovulatory hCG, patient selection, and the use of
      GnRH agonist pituitary desensitization in selected patients permits to limit
      multiple conceptions to a level comparable with the occurrence of this
      complication in normal unstimulated women.

PMID- 8735008
TI  - Age-dependent doses to members of the public from intake of radionuclides: Part
      4. Inhalation dose coefficients. A report of a task group of Committee 2 of the
      International Commission on Radiological Protection.

PMID- 8735009
TI  - The relation between long-period incremental markings in dentine and daily cross
      striations in enamel in human teeth.
AB  - Ground sections of human permanent teeth were chosen where fluorescent labels in
      the dentine, resulting from repeated doses of tetracycline antibiotic, were
      unambiguously associated with accentuated markings in the enamel developing at
      the same time. Counts of daily cross-striations in enamel were continued from one
      tooth to another in a developmental sequence over a period of some 1200 days such
      that the time interval between doses of tetracycline could be calibrated. Long
      period incremental markings in the dentine, spaced on average between 15 and 30
      microns apart (and first described by Andresen in 1898) were easily visible in
      the coronal dentine when the ground sections were viewed with polarized light.
      The total number of long-period incremental markings in the dentine between the
      consecutive fluorescent labels was also counted. A regression plot of daily
      incremental lines in enamel against long-period lines in dentine demonstrated a
      regular and consistent relation between the two (r = 0.997) over a 1200-1300-day
      period. These data support the hypothesis that long-period markings in dentine
      are in fact regular incremental markings with a constant periodicity in an
      individual. They also suggest that regular long-period markings in dentine can be
      used to reconstruct the timing of tooth growth or to retrieve developmental
      information about dentine formation rates in forensic, archaeological and
      palaeontological studies with some confidence.

PMID- 8735010
TI  - Selected salivary-gland cell culture and the effects of isoproterenol, vasoactive
      intestinal polypeptide and substance P.
AB  - To establish a selected salivary-gland cell culture and determine the effect of
      neuropeptides, monolayers were cultured using 3T3 cells as a feeder layer. To
      confirm the origin of these cultured cells, amylase production was examined by
      electron microscopy and periodic acid-Schiff staining, together with
      immunocytochemical analysis of myosin, anti-cytokeratin (CK-1, CK 10/13, CK
      MNF116, CK LMW, CK HMW and CK-19) and amylase antibody. The cultured cells
      demonstrated secretion granules containing amylase and presented features
      characteristic of acinar cells, which they retained until passage two. By using a
      feeder layer in conjunction with a newly formulated culture medium, the
      selectability of these cells was improved. Changes in proliferation of cultured
      salivary-gland cells in the presence of selected neurotransmitters were also
      examined. Isoproterenol enhanced cellular proliferation. On the other hand,
      vasoactive intestinal polypeptide and substance P, which increase the weight of
      salivary glands in vivo, showed no significant enhancement of proliferation.

PMID- 8735012
TI  - Effect of in vitro passage of healthy human gingival fibroblasts on cellular
      morphology and cytokine expression.
AB  - Cytokines have been implicated in the regulation of antibody and inflammatory
      responses, but their role in periodontal diseases has not been elucidated. In the
      present study, cytokine production by human gingival fibroblasts (HGF) following
      in vitro passage was assessed in order to determine the basal levels of cytokine
      message and protein and to determine if the cellular morphology and the profile
      of cytokines produced differed with passage. The HGF cell line F-CL was
      established by explantation from non-inflamed gingival tissue, and cells from
      passages 1-10 were studied. The number of cells was determined in confluent
      cultures and cell morphology was examined by light microscopy. Fibroblasts from
      confluent cultures were examined for cytokine mRNA by reverse transcription
      polymerase chain reaction and culture supernatants were assessed for cytokines by
      enzyme-linked immunosorbent assay. The morphology of F-CL fibroblasts in passages
      1-4 was normal, while fibroblasts in passages 5-10 were larger. In general, the
      number of cells decreased from early to late passage. Fibroblasts from passages 1
      10 contained message for interleukin-1 beta, -6 and -8, but not for interleukin-1
      alpha or tumour necrosis factor-alpha. Interleukin-6 was detected in culture
      supernatants of F-CL fibroblasts by the enzyme immunoassay and its level
      decreased with increasing passage.

PMID- 8735011
TI  - Expression of mRNA for matrix metalloproteinases and tissue inhibitors of
      metalloproteinases in periodontitis-affected human gingival tissue.
AB  - It is known that the host responds to an increased concentration of collagenase
      [or matrix metalloproteinase (MMP)-1] by preferentially expressing mRNA for the
      tissue inhibitor of metalloproteinase-1 (TIMP-1) in order to overcome tissue
      destruction due to periodontitis. To further elucidate the relation between MMPs
      and TIMPs in periodontitis-affected tissues, the expression of mRNA for MMP-1, -3
      and -8, and TIMP-1 and -2, in 10 gingival samples from patients and five from
      healthy individuals was assessed by reverse transcription-polymerase chain
      reaction. The diseased group showed significantly higher levels of MMP-1, -3, -8
      and TIMP-1 mRNA relative to beta-actin than the control group (mean +/- SE:
      diseased vs healthy (%): 0.26 +/- 0.05 vs 0.018 +/- 0.0040 for MMP-1; 0.09 +/-
      0.16 vs 0.063 +/- 0.016 for MMP-3; 0.068 +/- 0.017 vs 0.006 +/- 0.0010 for MMP-8;
      12.66 +/- 2.90 vs 2.71 +/- 0.54 for TIMP-1; p < 0.01). TIMP-2 did not
      significantly differ between the two groups (1.79 +/- 0.33 vs 1.42 +/- 0.53; p >
      0.05). The preferential increase in the level of MMP-3 mRNA relative to that of
      MMP-1 and -8 in inflamed gingiva would be relevant to tissue destruction because
      MMP-3 is a broad-spectrum MMP and a pivotal activator of latent MMP-1 and -8.
      Therefore, the overall increase in MMP-1, -3 and -8 mRNA in periodontitis
      affected gingiva might account for a concerted action of MMPs during connective
      tissue destruction in periodontitis.

PMID- 8735013
TI  - Associations between dietary intake, dental caries experience and salivary
      bacterial levels in 12-year-old English schoolchildren.
AB  - A population of 328 12-yr-old English schoolchildren, consuming their normal
      diets, was investigated in a cross-sectional study to determine the interactions
      between caries experience, oral hygiene status as gingival index (GI), dietary
      intake (as number of eating events per day and the number of eating events per
      day at which sugar-containing foodstuffs, confectionery or starch-containing
      foods were consumed) and salivary levels of caries-associated micro-organisms
      (mutants streptococci, lactobacilli and yeasts). The mean (+/- SD) decayed,
      missing and filled surfaces (DMFS) (excluding precavitation lesions) score was
      3.05 +/- 3.85 and 5.72 +/- 5.00 (including precavitation lesions). The DMFS
      scores were significantly related to the salivary levels of caries-associated
      micro-organisms and to the number of eating events per day for total number of
      eating events and the number of eating events at which sugar-containing foods or
      confectionery were consumed. These associations were apparent in both bivariate
      and partial correlation coefficients with the caries-associated micro-organisms
      and GI controlled. The total daily intakes of food types, except for starch, were
      not associated with caries experience. No significant correlations were found
      between intake of food types and salivary levels of caries-associated micro
      organisms except that the mean number of confectionery-eating events was
      correlated with lactobacillus levels (r = 0.136, p < 0.01). The salivary levels
      of mutans streptococci, lactobacilli and yeasts were significantly correlated
      with GI scores. These data do not indicate simple associations between dietary
      intake, caries and levels of caries-associated micro-organisms. Poor oral
      hygiene, in children consuming unrestricted diets, may influence the salivary
      levels of mutans streptococci, lactobacilli and yeasts irrespective of the
      frequency or amount of sugar consumed. Multiple regression analyses revealed that
      three variables--GI (probably an indicator of toothbrushing behaviour with a
      fluoride-containing toothpaste), salivary concentration of lactobacilli and
      frequency of ingestion of confectionery/sugary foods--were independently and
      positively related to caries experience.

PMID- 8735014
TI  - A comparison of the mineral content of enamel and dentine in human premolars and
      enamel pearls measured by X-ray microtomography.
AB  - Mineral content gradients in two composite enamel pearls from permanent human
      upper molars were measured by X-ray microtomography (XMT) at a resolution of 15
      30 microns. This non-destructive microscopic technique was used to make 15
      microns thick XMT slices with 100-microns separation through one pearl and 250
      microns separation through the other. Average mineral contents were calculated
      from the linear absorption coefficients determined from regions of the XMT slices
      assuming the inorganic component to be calcium hydroxyapatite. These values were
      compared with similar XMT studies of coronal enamel and dentine of upper
      permanent premolars. A mineral content gradient in the pearls, reducing from the
      enamel surface to the amelodentinal junction, was found; this was similar to that
      observed in the coronal enamel of the upper premolar. The mineral contents in the
      surface and deeper enamel regions of the pearl were similar to those observed in
      premolar enamel. In contrast, the mineral content for the dentine of the pearl
      was greatest at the amelodentinal junction, i.e. the gradient was in the opposite
      direction to that observed in premolar dentine. These results suggest that the
      process of mineralization of the pearl dentine differs from that in permanent
      control dentine. In addition, gradients in enamel and dentine mineral contents
      reducing from the tip of the pearl to the base of the pearl were found.

PMID- 8735016
TI  - An immunohistochemical investigation of the expression of parathyroid hormone
      receptors in rat cementoblasts.
AB  - Cementoblasts share many of the features of the osteoblast phenotype. To
      investigate their expression of cell surface receptors for parathyroid hormone
      (PTH) (i) unlabelled PTH was bound to tissue sections and subsequently detected
      with anti-PTH monoclonal antibodies; and (ii) digoxigenin (DIG)-labelled PTH was
      applied to the sections and the bound hormone detected with anti-DIG antibodies.
      The use of non-radioactive DIG-labelled PTH represents a novel approach for the
      immunodetection of PTH receptors in situ. The expression of PTH binding sites by
      cementoblasts of cellular, but not acellular, cementum was demonstrated. The
      immunoreactivity was weaker than that seen in osteoblasts, and mainly confined to
      cementoblasts of fully formed roots. These results suggest that cementoblasts of
      functional erupted teeth may be responsive to PTH stimulation and further support
      the idea that cementoblasts and osteoblasts share a similar phenotype.

PMID- 8735015
TI  - Interactions of streptococcal glucosyltransferases with alpha-amylase and starch
      on the surface of saliva-coated hydroxyapatite.
AB  - The salivary pellicle consists of various proteins and glycoproteins which may
      interact with one another. Experiments were performed to elucidate the
      interactions of streptococcal glucosyltransferase (Gtf) enzymes with human
      salivary alpha-amylase in solution and on the surface of saliva-coated
      hydroxyapatite (SHA) beads. The Gtf enzymes -B, -C and -D, when immobilized on to
      SHA beads, reduced the activity of adsorbed amylase; GtfD showed the highest
      inhibition of salivary amylase activity. The presence of glucan produced by
      immobilized GtfD did not further reduce amylase activity. The amount of amylase
      adsorbed on to hydroxyapatite beads was reduced when salivary amylase was added
      simultaneously with any of the Gtf enzymes, suggesting that amylase and Gtfs may
      compete with each other for binding sites on hydroxyapatite. Starch hydrolysates
      produced by SHA-surface-bound salivary amylase were tested for their effect on
      glucan production from sucrose by Gtf enzymes in solution and on SHA beads;
      glucan production by SHA-immobilized GtfB was stimulated in the presence of
      starch hydrolysates. Glucan synthesized by SHA-immobilized GtfB in the presence
      of starch hydrolysates was less susceptible to hydrolysis by the fungal enzyme
      mutanase than was glucan made by SHA-immobilized GtfB in the absence of starch
      hydrolysates. Glucan production by GtfB associated with streptococci immobilized
      on to SHA was also enhanced in the presence of starch hydrolysates. The adhesion
      of oral micro-organisms to SHA coated with glucan made in the presence and
      absence of starch hydrolysates was investigated, and some bacteria displayed
      higher adhesion activities for the glucan made in the presence of the
      hydrolysates. Therefore, the interaction of amylase and Gtf enzymes on a SHA
      surface may modulate the formation of glucan and the adherence of oral micro
      organisms.

PMID- 8735018
TI  - Detection of Mycoplasma fermentans in human saliva with a polymerase chain
      reaction-based assay.
AB  - Mycoplasma fermentans and other mycoplasma species may be associated with human
      immunodeficiency virus infection. Little is known about the ecology of this micro
      organism and its natural habitat. A polymerase chain reaction (PCR)-based assay
      was used to detect M. fermentans in whole saliva. The hypothesis was tested that
      M. fermentans is present on the mucosal surfaces of the mouth and oropharynx.
      Whole saliva was collected from 110 adults. The 206-bp amplification product of
      DNA purified from these samples was detected in ethidium bromide-stained 6%
      polyacrylamide gels in 49 (44%) samples tested. All samples were confirmed by
      Southern blotting with a probe based on an internal sequence of the expected
      amplification product. The data suggest that this organism is often found in
      saliva and on oropharyngeal mucosal surfaces. Saliva may play a part in its
      transmission between individuals. Saliva sampling may be helpful in further
      studies of the ecology and distribution of the micro-organism in human
      populations.

PMID- 8735017
TI  - The oral prevalence of aerobic and facultatively anaerobic gram-negative rods and
      yeasts in semi-recluse human vegetarians.
AB  - Limited data exist on the oral ecology of vegetarians. Hence the dental and
      periodontal status, and the oral prevalence of aerobic and facultatively
      anaerobic Gram-negative rods (AGNR) and yeasts, were studied in 36 semi-recluse,
      vegetarian, Buddhist monks and nuns in Hong Kong. The oral prevalence of AGNR and
      yeasts was 61.1% and 33.3%. There was no correlation between the prevalence of
      AGNR and/or yeasts and the incidence of carious or filled teeth and the health
      status of the periodontium. Rather, the results of this study combined with those
      of previous studies suggest that increasing age and the consumption of food
      prepared in communal kitchens might be more important contributory factors in the
      oral prevalence of AGNR than the nature of the diet itself or the health of the
      dentition and periodontium.

PMID- 8735020
TI  - ENZEDUC 1.0: a user-friendly software package for computation of hyperbolic
      enzyme kinetic data in biochemical education.
AB  - ENZEDUC 1.0 is a software package developed in Microsoft QuickBASIC v7.1 for
      computation of hyperbolic enzyme kinetics. The educational focus of the package
      is laboratory practical teaching. The program can manage a maximum of 18
      substrate concentration values and 72 reaction rate values for each substrate
      concentration (1296 pairs of values). Samples can also be of unequal sizes. More
      than one reaction rate value for each substrate concentration can be handled.
      Real-time screen plots are obtained for the Michaelis-Menten function and the
      most popular linear transformations. Printer outputs are available. Hardware
      requirements are minimum 640 Kb RAM, EGA graphics card and 80286 processor.

PMID- 8735019
TI  - A flexible high-precision video system for digital recording of motor acts
      through lightweight reflex markers.
AB  - This paper describes and evaluates the digital MacReflex system for wireless
      recording of movements in three dimensions. Up to seven high resolution infra-red
      sensitive CCD video cameras with electronic shutters register the positions of
      maximally 40 stroboscopically illuminated retro-reflective tape markers. The
      system is equipped with real-time video processors for computation of position co
      ordinates for the markers and for optimised data transmission and storage. Data
      are output to any type of computer through a standard serial interface, which
      also provides possibilities for simultaneous A/D-sampling. Dynamic manipulation
      of the recorded signals in three-dimensional plots is provided by standard
      software and transformation and evaluation of recorded data are performed in
      standard software. The described equipment is found to offer a flexible and
      easily operated solution for recording of movements with high resolution.

PMID- 8735021
TI  - A computer program for sample size and power calculations in the design of multi
      arm and factorial clinical trials with survival time endpoints.
AB  - This paper presents a computer program for use in the design of long-term
      clinical trials with multiple treatment arms in which the primary outcome
      variables are censored survival times. The treatment arms may be structured as a
      one-way or multi-way factorial design. It is assumed that patients are entered
      and randomized to a treatment arm during an accrual period. The patients are then
      followed for a fixed period during which there may be dropouts. Various
      distributional assumptions can be used to model the survival times. These include
      an option in which there is an effect of treatment duly after a lag or delay
      time. The program then computes the power of various statistical tests of
      hypotheses concerning treatment differences, interactions and trends. The power
      computations are "exact" in that they use the Monte Carlo method to obtain Type I
      and II error probabilities. However the program also outputs the normal
      approximations for comparison, although they are typically not accurate in these
      situations. Fisher's LSD method is used to adjust for the multiple comparisons.
      By comparing the power for various sets of design parameters, such as sample
      size, numbers of factor levels, patient accrual rate, and length of follow-up, an
      appropriate design can be constructed. Two examples are provided. The first is a
      simple one-way layout with multiple treatment arms; the second a two-way
      factorial design for a proposed large scale cancer chemoprevention trial.

PMID- 8735022
TI  - Computer aided data acquisition and analysis of acetlycholinesterase velocity
      sedimentation profiles.
AB  - Acetylcholinesterase (AChE) is an enzyme that appears in several molecular forms.
      Individual AChE molecular forms can be isolated and identified on the basis of
      their velocity sedimentation profiles. We have improved an existing method for
      analyzing AChE sedimentation profiles with a computer aided data acquisition and
      analysis system. The software facilitates measurements of AChE activity of
      individual molecular forms and comparison among AChE velocity sedimentation
      profiles. In practice, our program increased precision and reduced the time of
      AChE velocity sedimentation profile analysis. The software can also be applied to
      velocity sedimentation analysis of other proteins. We plan to upgrade the program
      by making it compatible with Microsoft Windows.

PMID- 8735023
TI  - MIXOR: a computer program for mixed-effects ordinal regression analysis.
AB  - MIXOR provides maximum marginal likelihood estimates for mixed-effects ordinal
      probit, logistic, and complementary log-log regression models. These models can
      be used for analysis of dichotomous and ordinal outcomes from either a clustered
      or longitudinal design. For clustered data, the mixed-effects model assumes that
      data within clusters are dependent. The degree of dependency is jointly estimated
      with the usual model parameters, thus adjusting for dependence resulting from
      clustering of the data. Similarly, for longitudinal data, the mixed-effects
      approach can allow for individual-varying intercepts and slopes across time, and
      can estimate the degree to which these time-related effects vary in the
      population of individuals. MIXOR uses marginal maximum likelihood estimation,
      utilizing a Fisher-scoring solution. For the scoring solution, the Cholesky
      factor of the random-effects variance-covariance matrix is estimated, along with
      the effects of model covariates. Examples illustrating usage and features of
      MIXOR are provided.

PMID- 8735024
TI  - Effects of a supportive protocol processing system (ProtoVIEW) on clinical
      behaviour of residents in the accident and emergency department.
AB  - A randomized two period crossover trial was performed at the Accident and
      Emergency (A & E) department of the University Hospital in Nijmegen (The
      Netherlands). We assessed what the impact was of (mandatory) consultation of a
      protocol for the management of isolated traumas on treatment decisions of
      residents. All eight surgical residents who regularly worked in the A & E
      department participated in the trial. All patients who entered the A & E
      department between October 13, 1992 and June 9, 1993, of age 16 years or older
      with an isolated fracture without concomitant lesions were admitted to the study.
      During the experimental periods, the management protocol was available on
      computer (using ProtoVIEW) and during the control periods on paper. Main
      measurements were treatment adjustments made by residents (after consulting
      different information sources), and their opinion about ProtoVIEW as an
      information source assessed by means of a questionnaire. When protocol
      consultation was mandatory, residents changed their treatments almost four times
      more often towards the protocol than during the control periods (P = 0.01 Chi
      square test). Most residents found ProtoVIEW easy to use, liked it as a useful
      training source while half of them said they would use the system in daily
      clinical practice. We conclude that mandatory protocol consultation using
      ProtoVIEW influenced protocol adherence positively.

PMID- 8735025
TI  - Skill-mix in clinical radiology.

PMID- 8735026
TI  - Gender stereotyping: consequences for mental health care.

PMID- 8735027
TI  - Current management of congestive heart failure.
AB  - Congestive heart failure is a major public health problem in developed countries.
      There have been significant advances in the management of this condition over the
      last few decades. However, many patients are still not receiving adequate
      therapy. Optimal management requires appropriate investigation, education,
      counselling, medical treatment and planned follow-up. This review outlines the
      recommended approach for optimal management of patients with heart failure.

PMID- 8735028
TI  - How to get a job in medicine: 1.
AB  - Medical graduates need to plan their careers. When choosing your next job, ask
      for advice and select carefully. Your curriculum vitae must present your
      experience and special qualities to your best advantage.

PMID- 8735029
TI  - The role of nuclear medicine in the investigation of patients with AIDS.
AB  - HIV-positive patients are susceptible to both opportunistic infection and
      malignant disease. Radionuclide techniques can help in the detection of the
      occult infection and in the differentiation between infection and tumour.

PMID- 8735030
TI  - Functional endoscopic sinus surgery.
AB  - Functional endoscopic sinus surgery (FESS) is a minimally invasive dissection
      technique of in which the air cells and ostia of the paranasal sinuses are opened
      under direct vision via an endoscope. This article considers the relevant
      surgical anatomy, indications, techniques and potential complications of FESS.

PMID- 8735031
TI  - Stress in the workplace.

PMID- 8735032
TI  - Occupational stress and the law: some current issues for employers.

PMID- 8735033
TI  - Post-traumatic stress disorder.

PMID- 8735034
TI  - Chronic fatigue syndrome: a stress disorder?

PMID- 8735035
TI  - The pelvic floor sequelae of childbirth.
AB  - For centuries the structure and function of the pelvic floor and anal sphincter
      have remained enigmatic. Great strides made in new imaging techniques over the
      last decade has enabled a better understanding of this complex and dynamic
      structure. We can now explore pelvic floor dysfunction.

PMID- 8735037
TI  - Recent advances in speech and language therapy.
AB  - Speech and language therapists are involved in the care of a wide range of
      pathogies. Recent changes have been marked by an increased involvement in feeding
      and swallowing work with premature babies, and oropharyngeal cancer sufferers.
      Changes have also occurred in assessment and management of communication problems
      resulting from acquired neurological pathologies such as stroke, Parkinson's
      disease and dementia. Some of these are discussed in the following article.

PMID- 8735038
TI  - Analgesia and analgesic drugs in paediatrics.
AB  - This article reviews the management of acute and chronic pain in childhood. Many
      of the common problems are discussed and the range of therapeutic options are
      reviewed, including possible future advances. The management of pain in neonates
      is not discussed. The second article of this series will describe the use of
      sedative drugs in paediatric practice.

PMID- 8735039
TI  - Organizational development.
AB  - Organizational development is a widely used concept in industry and the NHS. It
      tends to be associated with the softer side of management, and this often masks
      the complex set of ideas it represents. Its currency in the NHS has risen,
      especially in the last decade, because its application in practice is closely
      linked to the process of managing change. This article reviews the definitions of
      organizational development and explains how the concept can be used to underpin
      organizational change.

PMID- 8735040
TI  - Emergency laparoscopy in a patient with severe asthma.

PMID- 8735041
TI  - Revisiting the psychological aspects of AIDS.

PMID- 8735042
TI  - Outpatient laparoscopic cholecystectomy feasibility.
AB  - One-hundred nineteen elective cholecystectomies were performed at Kern Medical
      Center over a 20-month period from October 1992 to May 1994 and were
      retrospectively reviewed. Eight males and 111 females ranged in age from 16 to
      70. Laparoscopic cholecystectomy was attempted in 116 patients and converted to
      open in 8 (7%). Of the elective procedures, 108 (91%) were planned as outpatient
      procedures. Of the 108 planned outpatient procedures, 73 (68%) were successfully
      completed as outpatients. Of the 35 patients who required unplanned admission, 21
      were discharged in less than 24 h. In total, 101 (87%) of the 116 elective
      cholecystectomies begun laparoscopically were discharged in less than 24 h.
      Subsequent to this data analysis, our institution is developing a 23.9 h "day
      hospital" for postanesthesia observation. With extended postoperative monitoring
      and observation, patients with short-term problems such as nausea, vomiting,
      pain, and even patients with medical conditions requiring close observation and
      control should be able to avoid admission. This retrospective study indicates
      that with development of a 23.9 h postanesthesia care unit, the majority of
      elective cholecystectomies can be attempted and completed laparoscopically on an
      outpatient basis.

PMID- 8735043
TI  - Outpatient cholecystectomy.
AB  - One hundred consecutive patients requiring elective cholecystectomy in one
      surgeon's practice were booked as outpatients between April 1994, and July 1995.
      Two patients had massive adhesions and 18 had acute disease. Outpatient surgery
      was successful for 94 patients, who spent an average of less than 6 h in
      hospital. Six patients required postoperative admission, four because of
      conversion and two for other causes. There were three readmissions, unrelated to
      outpatient status: one to treat a wound infection, one to drain a subphrenic
      abscess, and one to repair an umbilical hernia. Complications were one subphrenic
      abscess, one case of significant atelectasis, and, at the umbilical incision
      seven wound infections, one hematoma and one postoperative hernia. Advanced age
      and increased comorbidity correlated significantly with the need for hospital
      admission, but were not contraindications, either alone or in combination, to
      outpatient surgery. Patient satisfaction was high.

PMID- 8735044
TI  - Early experience with laparoscopic splenectomy.

PMID- 8735045
TI  - A case-control study of postoperative pulmonary complications after laparoscopic
      and open cholecystectomy.
AB  - Postoperative pulmonary complications (PPC) are common after upper abdominal
      surgery. The objective of this case-control study was to compare the incidence of
      PPC after laparoscopic cholecystectomy (LC) and open cholecystectomy (OC) within
      a tertiary care center. Patients were accrued from two sequential clinical trials
      that evaluated the role of incentive spirometry in the prevention of PPC after
      abdominal surgery. Included for study were patients with gallstones undergoing
      elective surgery who had an American Society of Anesthesiologists (ASA)
      classification < 3. All patients included in the study were encouraged to use an
      incentive spirometer at least 10 times each hour while awake. Patients with
      chronic bronchitis were excluded from study, as were patients who received other
      forms of physical therapy. OC was performed through either a transverse or an
      oblique incision. There was an equitable dispersion of putative risk factors for
      PPC between the groups at baseline. PPC were defined as clinical features
      consistent with collapse/consolidation, an otherwise unexplained temperature
      above 38 degrees C, plus either confirmatory chest radiology or positive sputum
      microbiology. The incidence of PPC was 2.7% (1/37) after LC and 17.2% (10/58)
      after OC (p < 0.05). It is concluded that PPC are less common after laparoscopic
      cholecystectomy than after open cholecystectomy.

PMID- 8735046
TI  - Comparative stress hormone changes during helium versus carbon dioxide
      laparoscopic cholecystectomy.
AB  - Laparoscopic surgery has been termed minimally invasive surgery by advocates of
      this technology. It has been demonstrated previously that using carbon dioxide
      for insufflation produces a respiratory acidosis due to transperitoneal
      absorption of gas. Insufflation with helium does not create this acidosis. We
      questioned whether laparoscopic surgery would elicit a stress response and
      whether the absence of acidosis with helium might prevent or reduce the levels of
      stress hormones. Sixteen female patients undergoing laparoscopic cholecystectomy
      were randomly assigned to helium (n = 8) or CO2 (n = 8) insufflation. Serum
      cortisol, epinephrine, and norepinephrine were measured preoperatively, after
      induction of anesthesia but before insufflation, at 45 min of surgery, and after
      desufflation. There were increases in epinephrine, norepinephrine, plasma
      cortisol, and urine cortisol at 45 min and at the conclusion of the procedure
      over the preoperative value. With ANOVA, each variable showed significant
      increases from preoperative values, at 45 min, and at the end of the case. Except
      for the increased epinephrine when helium was used, there were no significant
      differences in the other variables between helium and CO2. Laparoscopic
      cholecystectomy produces significant increases in stress hormone levels.
      Prevention of acidosis with helium insufflation does not appear to protect
      against increases in stress hormones. Epinephrine levels with helium insufflation
      are higher than with CO2, and elevations in stress hormones suggest that
      laparoscopic cholecystectomy is not physiologically minimally invasive.

PMID- 8735047
TI  - Safety evaluation of laparoscopically applied clips.
AB  - We have evaluated in vitro, the security of laparoscopically applied clips,
      through two commercially available clip appliers: the Endo Clip II (US Surgical)
      and the Ligaclip (Ethicon). The clip performance was tested with respect to
      dislodgment and leakage. Dislodgment was attempted both transversely and at 45
      degrees with respect to the main axis of the tubular structures tested. The mean
      maximum force (N = 24) necessary to dislodge a clip applied to silicone tubing
      (2.1, 2.4, 3.2 mm o.d.) and porcine vascular tissue was measured. The maximum
      force needed to transversely dislodge a clip applied to silicone tubing, ranged
      from 262 +/- 9 g (2.1 mm) to 315 +/- 11 g (3.2 mm) for the Endo Clip II applier,
      while the values for the Ligaclip were 220 +/- 28 g (2.1 mm) and 273 +/- 11 g
      (3.2 mm), respectively. To achieve dislodgment at 45 degrees pull, corresponding
      forces of 294 +/- 8 g (2.1 mm) and 369 +/- 14 g (3.2 mm) for the Endo Clip II,
      and 254 +/- 14 g (2.1 mm) and 297 +/- 13 g (3.2 mm) for the Ligaclip (N = 24)
      were required. Transverse dislodgment forces, for clips applied to tissue, were
      556 +/- 146 g for the Endo Clip II and 356 +/- 170 for the Ligaclip (N = 6).
      Leakage tests were also performed under pulsatile blood circulation at mean
      pressure of approximately 800 mm Hg. No tested clips applied to either silicone
      tubing or tissue allowed for any blood leakage. The dislodgment test showed that
      the Endo Clip II exhibits superior performance compared to the Ligaclip, based on
      the fact that it requires more force for transverse and semiaxial dislodgment. In
      the leakage test, both clip appliers performed equivalently.

PMID- 8735048
TI  - The use of T-bars in laparoscopic ventral hernia repair.
AB  - During the past 2 years 15 laparoscopic ventral hernias have been performed at
      our Community Hospital. Marlex mesh has been the material used. We have noticed
      some difficulty with the grasping and initial anchoring of the mesh.
      Percutaneously placed prolene sutures allow the mesh to be drawn upward with some
      effort. By using laparoscopic T-bars for the initial anchoring of the mesh to the
      anterior abdominal wall then stapling, the operative time was greatly reduced.
      This modification in technique allows for quicker placement of the mesh during
      the repair.

PMID- 8735049
TI  - A technique for second-look laparoscopy in the obese patient.
AB  - A technique for second-look laparoscopy in an obese patient suffering from acute
      mesenteric ischemia is described. A device composed of a 10-mm trocar-sleeve and
      a large Foley catheter was used, which enables its proper fixation through the
      abdominal wall, without causing any intestinal damage.

PMID- 8735050
TI  - Surgical decisions in the laparoscopic management of small bowel obstruction:
      report on two cases.
AB  - Laparoscopic management of bowel obstruction secondary to adhesions presents a
      difficult challenge for the general surgeon. The surgical management of two such
      cases is reported here: one patient with recurrent abdominal pain secondary to
      partial bowel obstruction, the other with acute small bowel obstruction. Surgical
      decision-making and technical aspects of the procedures are described. With
      careful patient selection and meticulous technique laparoscopic resolution of
      bowel obstruction may be feasible and should be attempted.

PMID- 8735051
TI  - Empyema from lost gallstones: a thoracic complication of laparoscopic
      cholecystectomy.
AB  - Laparoscopic cholecystectomy may result in lost (dropped) gallstones. Such stones
      may precipitate abdominal abscesses including subphrenic abscesses. In our case,
      the abscess eroded through the diaphragm causing an empyema 17 months after the
      laparoscopic cholecystectomy. Treatment included decortication, drainage, and
      removal of the stones.

PMID- 8735052
TI  - Laparoscopic conversion of polya gastrectomy to Roux-en-Y.
AB  - We describe a patient who underwent laparoscopic conversion of a Polya
      gastrectomy to a Roux-en-Y. We used the "Endo Stitch" (Autosuture Co., Ascot, UK)
      to simplify the creation of a laparoscopic anastomosis. The patient required
      minimal analgesia and made a rapid and uncomplicated recovery.

PMID- 8735053
TI  - Laparoscopic transabdominal preperitoneal repair of a hernia of Morgagni.
AB  - A hernia of Morgagni was successfully repaired laparoscopically by reducing the
      hernia, mobilizing the peritoneum around the perimeter of the defect, and
      stapling polypropylene mesh onto the surrounding fascia. This type of repair is
      technically easy and should give a high probability of success.

PMID- 8735054
TI  - Three-trocar laparoscopic cholecystectomy.

PMID- 8735055
TI  - Music improves emotional awareness.

PMID- 8735056
TI  - How to excel as a teacher of geriatrics.

PMID- 8735057
TI  - Learning and teaching styles: implications for teachers of family medicine.
AB  - BACKGROUND: Much attention has been given to learning and teaching "styles" in
      adult education and in medical education. Since style refers to assumptions and
      beliefs about how adults learn, it affects what teachers do to facilitate
      learning. A synthesis of two models views the educational process as a cycle:
      "experience," followed by "reflection," "abstraction," and "experimentation."
      Four styles of learning or teaching are possible by combining experience with
      observation, observation with abstraction, abstraction with experimentation, and
      experimentation with experience. Students and residents could use this
      information to negotiate with faculty to best meet their educational needs, and
      faculty could use this information to tailor their teaching strategies to best
      suit each encounter.

PMID- 8735058
TI  - Community-oriented primary care in a family practice residency program.
AB  - BACKGROUND: The practice of medicine needs to include disease prevention, health
      promotion, community health, and clinical epidemiology. Community-oriented
      primary care (COPC) can be used as an educational strategy to develop
      competencies in these areas. METHODOLOGY: An interdisciplinary team that included
      public health representatives was created to teach COPC principles to family
      practice residents and supervise their community projects. Allied health and
      nursing graduate students were also involved in the process. Projects were
      implemented in collaboration with community representatives. RESULTS: Family
      practice residents and community representatives were positive about working
      together. The family practice residents appreciated the interdisciplinary
      experience and reported that the COPC model will be useful to them in the future.
      However, the program's didactic phase was insufficient to provide adequate skills
      for use of the COPC process. The program could benefit from more involvement of
      medical students and students in other health professions. CONCLUSIONS: The
      program encountered several significant obstacles such as competing clinical
      priorities, limited health education skills, and inadequate project evaluations.
      Despite the challenges, the family practice residents, as well as the
      interdisciplinary faculty, health science graduate students, and community
      representatives, reported a positive experience.

PMID- 8735059
TI  - Teaching smoking cessation to family practice residents: an experiential
      approach.
AB  - BACKGROUND AND OBJECTIVES: Smoking cessation is a complex process influenced by
      the smoker's motivation to quit and the effective use of external support
      measures. Understanding the complexities of smoking cessation can be difficult
      for physicians, many of whom have never smoked. This paper describes an
      experiential educational approach that exposes family practice residents to the
      process of smoking cessation through active participation in an American Lung
      Association (ALA) Freedom From Smoking group. METHODS: We designed and observed a
      1-month educational program in which residents co-led a modified ALA group.
      Ethnography, a qualitative research technique, was used to discover what
      residents learned. RESULTS: We identified five themes that describe what
      residents learned through their experience in the ALA Group: 1) the power of
      nicotine addiction, 2) the power of the smoking cessation group, 3) skills, tips,
      tools, and tricks to help the smoker quit, 4) the process of redefining success,
      and 5) the ability to understand the smoker. Residents' recall of their
      experience remained vivid, even 9 months after the training concluded.
      CONCLUSIONS: This experiential approach provided a rich, lasting learning
      experience for the residents we studied.

PMID- 8735060
TI  - First-year medical students' knowledge of and attitudes toward primary care
      careers.
AB  - BACKGROUND AND OBJECTIVES: This study compared the knowledge of and attitudes
      toward primary care in relation to anticipated career choices of first-year
      medical students at two medical schools that differ significantly in production
      of primary care physicians. METHODS: A cross-sectional survey was conducted at a
      private, urban school in the Northeast where only a small percentage of students
      enter family practice residencies and a public, rural school in the Southeast
      where entry into family practice is among the highest in the country. The survey
      was conducted during the first semester of medical school. RESULTS: Ninety-six
      percent of students correctly identified general internal medicine, general
      pediatrics, and family practice as primary care fields; 51.8% identified these
      fields as "specialties." Statistically significant differences were seen between
      the percentages of students at the two schools who planned careers in primary
      care, suggesting that selection processes may differ between the two schools.
      There were no significant differences between students at the two schools in
      correctly identifying the characteristics of primary care practice. Only minor
      differences between the schools were found in assessments of the need for or
      importance of primary care. CONCLUSIONS: Although a significant difference in
      student interest in becoming primary care physicians was detected at the two
      schools, a surprising similarity was shown in their knowledge and attitudes about
      primary care. New attitudinal markers will need to be developed to help
      admissions committees select students most likely to enter primary care careers.

PMID- 8735061
TI  - Do program directors and their chief residents view the role of chief resident
      similarly?
AB  - BACKGROUND: The chief resident plays an important role in family practice
      residencies and is positioned at the nexus of the relationship between the
      faculty and the residents. It is unknown if program directors and their
      respective chief residents view this position and the role of training and
      faculty development similarly. METHODS: Parallel surveys were sent to all family
      practice residency program directors and their respective chief residents to
      explore their perceptions of the importance of the tasks and roles of the chief
      resident and the effects that perceived training, feedback, and support have on
      the chief resident's satisfaction. RESULTS: Fifty-one percent of chief residents
      and their program directors returned surveys that could be analyzed in parallel.
      Program directors placed relatively greater importance on the administrative role
      of chiefs. Mentioned most frequently as problems were balancing administrative
      duties with other tasks, dealing with personnel issues, and working with the lack
      of a clear job description. Chiefs who participated in formal training programs
      and who perceived better burnout prevention were more satisfied with their
      position. CONCLUSIONS: A large number of chief residents perceived gaps in the
      preparation for their position, particularly with regard to administrative
      skills. These deficiencies are particularly ironic in light of program directors'
      perceptions that administrative duties are of the highest importance among the
      tasks assigned to chief residents. Faculty development strategies and a program
      of burnout prevention for chief residents should be incorporated into each
      residency.

PMID- 8735062
TI  - The influence of depression on physician-patient interaction in primary care.
AB  - BACKGROUND: Depression is common but not well diagnosed in primary care medicine.
      This study examines the influence of depression and its recognition on the
      physician-patient encounter. METHODS: A total of 508 new adult patients were
      assigned randomly to 105 primary care providers. Self-reported depression was
      determined by the Beck Depression Inventory (BDI) on entry to the study. Initial
      visits were videotaped and analyzed using the Davis Observation Code. Chart notes
      were reviewed for diagnosis of depression. RESULTS: Seventy-seven of the 508
      study patients (15%) were identified as depressed in chart notes, while 130
      patients (26%) had a BDI score > or = 9, indicating moderate to severe
      depression. Recognition of depression was associated with increased counseling,
      decreased time conducting physical examination, and an increase in overall visit
      length. Both elevated BDI scores and physician recognition of depression were
      associated with decreases in chatting. Failure to recognize depression was
      associated with increased time taking medical history. CONCLUSIONS: Results
      support the potential value of psychological screening instruments in primary
      care and provide information for training physicians in the recognition and
      management of depression. The content of office visits is different when patients
      are depressed or are diagnosed as depressed.

PMID- 8735063
TI  - Why do the elderly seek or avoid care? A qualitative analysis.
AB  - BACKGROUND AND OBJECTIVES: This study attempts to understand why the elderly seek
      or choose not to seek health care. Most studies on barriers to health care have
      measured obstacles defined by the researchers. We attempt to define variables
      that are relevant to the elderly but have not yet been articulated. METHODS:
      Using grounded theory, open-ended interviews of 15 non-housebound elderly were
      conducted and coded. The data obtained were analyzed to discover and characterize
      the subjects' perceptions of barriers. RESULTS AND CONCLUSIONS: The major theme
      that emerged involved the interactions among autonomy, self-esteem, and the
      degree of illness or health. The study generated two hypotheses: 1) Self-esteem
      is directly correlated with the willingness of the elderly to seek care,
      especially as illness increases and autonomy decreases. 2) The individual's
      perception of health status, the perceived roles of the physician and the
      patient, the physician-patient relationship, and systems issues contribute to the
      dynamic paradigm that positions the elderly patient to seek or avoid seeking
      health care.

PMID- 8735064
TI  - Academic achievement of successful candidates for tenure and promotion to
      associate professor.
AB  - BACKGROUND AND OBJECTIVES: For faculty to achieve promotion and tenure, a clear
      understanding is needed of the measures by which performance will be judged. This
      study describes the specific academic achievements of successful candidates for
      tenure and promotion to associate professor in family medicine. METHODS: A survey
      questionnaire was mailed to all members listed in the Society of Teachers of
      Family Medicine database as holding the rank of associate professor. The
      questionnaire sought information about items as they were at the time the
      individual was being considered for promotion to associate professor with tenure.
      The items included scholarly accomplishments, time for research, areas of
      scholarly expertise, and departmental policy regarding promotion and tenure.
      RESULTS: Of the 296 eligible faculty, 197 (67%) returned a completed survey. The
      mean number of publications of these successfully promoted individuals was 10.
      The respondents averaged 78% of their publications in peer-reviewed journals and
      were first author on 64% of their peer-reviewed articles. The mean number of peer
      reviewed publications per year was 1.5. Research grant support as principal or
      coinvestigator was reported by 44%, and respondents averaged 9 hours a week on
      scholarly activities. Scholarly activity was found to vary significantly by type
      of school, degree, and tenure track status. CONCLUSIONS: Information reported
      here can be of value for prospective promotion and tenure candidates, their
      advisors, and members of review committees.

PMID- 8735065
TI  - Lessons of a family medicine educator.

PMID- 8735066
TI  - Generators of the brainstem auditory evoked potential in cat. I. An experimental
      approach to their identification.
AB  - This paper is the first in a series aimed at identifying the cellular generators
      of the brainstem auditory evoked potential (BAEP) in cats. The approach involves
      (1) developing experimental procedures for making small selective lesions and
      determining the corresponding changes in BAEP waveforms, (2) identifying
      brainstem regions involved in BAEP generation by examining the effects of lesions
      on the BAEP and (3) identifying specific cell populations involved by combining
      the lesion results with electrophysiological and anatomical information from
      other kinds of studies. We created lesions in the lower brainstem by injecting
      kainic acid which is generally toxic for neuronal cell bodies but not for axons
      and terminals. This first paper describes the justifications for using kainic
      acid, explains the associated problems, and develops a methodology that addresses
      the main difficulties. The issues and aspects of the specific methods are
      generally applicable to physiological and anatomical studies using any
      neurotoxin, as well as to the present BAEP study. The methods chosen involved (1)
      measuring the BAEP at regular intervals until it reached a post-injection steady
      state and perfusing the animals with fixative shortly after the last BAEP
      recordings were made, (2) using objective criteria to distinguish injection
      related BAEP changes from unrelated ones, (3) making control injections to
      identify effects not due to kainic acid toxicity, (4) verifying the anatomical
      and functional integrity of axons in lesioned regions, and (5) examining injected
      brainstems microscopically for cell loss and cellular abnormalities indicating
      dysfunction. This combination of methods enabled us to identify BAEP changes
      which are clearly correlated with lesion locations.

PMID- 8735067
TI  - Generators of the brainstem auditory evoked potential in cat. II. Correlating
      lesion sites with waveform changes.
AB  - Brainstem regions involved in generating the brainstem auditory evoked potential
      (BAEP) were identified by examining the effects of lesions on the click-evoked
      BAEP in cats. An excitotoxin, kainic acid, was injected into various parts of the
      cochlear nucleus (CN) or into the superior olivary complex (SOC). The locations
      of the resulting lesions were correlated with the changes produced in the various
      extrema of the BAEP waveforms. The results indicate that: (1) the earliest BAEP
      extrema (P1, N1 (recorded between vertex and the earbar ipsilateral to the
      stimulus) and P1a, P1b, (vertex to contralateral earbar)) are generated by cells
      with somata peripheral to the CN; (2) P2 is primarily generated by posterior
      anteroventral CN (AVCNp) and anterior posteroventral CN (PVCNa) cells; (3) SOC,
      anterior anteroventral CN (AVCNa), AVCNp, and PVCNa cells are involved in
      generating P3; (4) AVCNa cells are the main CN cells involved in P4, N4, and P5
      generation; (5) both ipsilateral and contralateral SOC cells have a role in
      generating monaurally evoked P4 and P5; and (6) P5 is generated by cells with
      characteristic frequencies below 10 kHz. From (2) and (4), it is clear that P2
      and P4-P5 are generated by cells in distinct, parallel pathways.

PMID- 8735068
TI  - Generators of the brainstem auditory evoked potential in cat. III: Identified
      cell populations.
AB  - This paper examines the relationship between different brainstem cell populations
      and the brainstem auditory evoked potential (BAEP). First, we present a
      mathematical model relating the BAEP to underlying cellular activity. Then, we
      identify specific cellular generators of the click-evoked BAEP in cats by
      combining model-derived insights with key experimental data. These data include
      (a) a correspondence between particular brainstem regions and specific extrema in
      the BAEP waveform, determined from lesion experiments, and (b) values for model
      parameters derived from published physiological and anatomical information.
      Ultimately, we conclude (with varying degrees of confidence) that: (1) the
      earliest extrema in the BAEP are generated by spiral ganglion cells, (2) P2 is
      mainly generated by cochlear nucleus (CN) globular cells, (3) P3 is partly
      generated by CN spherical cells and partly by cells receiving inputs from
      globular cells, (4) P4 is predominantly generated by medial superior olive (MSO)
      principal cells, which are driven by spherical cells, (5) the generators of P5
      are driven by MSO principal cells, and (6) the BAEP, as a whole, is generated
      mainly by cells with characteristic frequencies above 2 kHz. Thus, the BAEP in
      cats mainly reflects cellular activity in two parallel pathways, one originating
      with globular cells and the other with spherical cells. Since the globular cell
      pathway is poorly represented in humans, we suggest that the human BAEP is
      largely generated by brainstem cells in the spherical cell pathway. Given our
      conclusions, it should now be possible to relate activity in specific cell
      populations to psychophysical performance since the BAEP can be recorded in
      behaving humans and animals.

PMID- 8735069
TI  - Effects of noise and exercise on distortion product otoacoustic emissions.
AB  - The effect of physical exercise on both distortion product otoacoustic emissions
      (DPOAE), and on the temporary effects of noise on human cochlear function was
      examined. Changes in DPOAEs were compared to changes in behavioural thresholds
      and the possible relation between contralateral suppression of DPOAEs and
      susceptibility to noise exposure was investigated. Bekesy audiometry,
      tympanometry and DPOAEs were measured in 8 subjects on 3 separate occasions:
      before and after noise exposure; before and after exercise at 60% of maximal
      oxygen uptake (VO2max); and before and after a combination of noise exposure and
      exercise, all of 10 min duration. Noise exposure was third-octave band noise of
      102 dB SPL centered at 2 kHz. The magnitude of the effect of noise exposure on
      DPOAE amplitude averaged in the 2-4 kHz range was comparable but weakly
      correlated to the magnitude of the temporary threshold shift (TTS) measured as
      the change in Bekesy threshold at 3 kHz. There was no effect of physical exercise
      without noise exposure on either the Bekesy threshold or the DPOAE amplitude.
      Physical exercise significantly increased the noise-induced TTS and the effect of
      noise exposure on DPOAE amplitude. A positive correlation was found between the
      temporary effect of noise exposure and the contralateral suppression effect on
      DPOAE amplitude.

PMID- 8735070
TI  - Multiple projections from the ventral nucleus of the trapezoid body in the rat.
AB  - An analysis of the central projections of the ventral nucleus of the trapezoid
      body (VNTB) in the rat, a region of the superior olivary complex known for its
      neuronal heterogeneity, was made using two anterograde axonal tracers,
      [3H]leucine and biotinylated dextran amine (BDA). A mixture of these tracers was
      injected iontophoretically into the VNTB and the results analyzed by first
      assessing magnitudes of autoradiographic signal in nuclei receiving projections
      and then identifying the axons and terminals responsible for this signal in
      parallel sets of sections processed for BDA. Our analysis showed that in addition
      to its projections to each cochlea via the olivocochlear bundle, the VNTB has 3
      major central sites of axonal terminations: (1) the cochlear nucleus,
      particularly the molecular layer of the contralateral dorsal cochlear nucleus,
      (2) the contralateral lateral superior olive, and (3) the ipsilateral inferior
      colliculus. Other sites receiving projections from the VNTB included the VNTB
      itself and the nuclei of the lateral lemniscus. Significantly, the relative
      magnitudes of labeling within the nuclei receiving inputs from the VNTB varied
      consistently as a function of the dorsoventral location of the injection site,
      confirming previous work showing that there is a partial segregation within this
      nucleus of neurons according to their projections. Our data also revealed an
      orderly topographic pattern of projections to the cochlear nuclei, lateral
      superior olive and the inferior colliculus which is consistent with the known
      tonotopic organization both of the VNTB and these projection targets.
      Methodologically, the co-injection of two tracers was advantageous in that
      patterns of silver grains in autoradiographs could be used to confirm whether
      axons and terminals labeled with BDA had originated from labeled somata at the
      injection site or were the result of uptake of BDA by fibers of passage.

PMID- 8735071
TI  - The midbrain creates and the thalamus sharpens echo-delay tuning for the cortical
      representation of target-distance information in the mustached bat.
AB  - Mustached bats emit complex biosonar 'pulses' for echolocation. A delay of an
      echo from the emitted pulse carries target-distance information. At the auditory
      periphery, distance information is expressed by a time interval between the
      responses of neurons to the emitted pulse and its echo. In the auditory cortex
      (AC), however, it is mapped by 'FM-FM' neurons which are tuned to particular echo
      delays. FM-FM neurons have been found not only in the AC but also in the inferior
      colliculus (IC) of the midbrain and the medial geniculate body (MGB) of the
      thalamus. In the present study, we found that the IC has a precursor of the
      cortical echo-delay axis for the systematic representation of target-distance
      information and that the MGB shows the improved neural representation of target
      distance information.

PMID- 8735072
TI  - Ultrastructural localization of G-protein GS in the lateral wall of the guinea
      pig cochlear duct.
AB  - Immunocytochemical localization of a GTP-binding protein, Gs, in the various
      cells of the lateral wall of guinea pig cochlear duct was investigated using a
      post-embedding immunogold method with antibody raised against a synthetic
      decapeptide (RMHLRQYELL) encoding the C-terminus of the alpha-subunit of Gs. In
      the stria vascularis, labeling was observed on the basolateral membrane
      infoldings of marginal cells, on the juxtaposed membrane of intermediate cells,
      and on the cell membrane of basal cell. In contrast, no significant labeling was
      observed on the luminal membrane of marginal cells. Immunoreactivity also was
      detected on the cell membranes of various other cells. These include spiral
      prominence epithelial cells, fibrocytes of spiral ligament, external sulcus
      cells, and epithelial and mesothelial cells of Reissner's membrane.
      Adenylylcyclase has been functionally implicated in some of the cell types with
      membranes labeled in this study. The significance of these findings is briefly
      discussed.

PMID- 8735073
TI  - Morphologic evidence for three cell types in the human spiral ganglion.
AB  - Although two types of spiral ganglion cells (large type I and smaller type II)
      have classically been described by anatomic studies in both animal and human
      spiral ganglion, there is physiologic and morphologic evidence for subtypes of
      the large type I ganglion cell. In addition, in the animal and human, a variety
      of morphologic differences based on cytoplasmic content, myelinization,
      immunostaining and morphometric analysis have suggested more than one variety of
      type I ganglion cell. Light and electron microscopic serial sections of the
      spiral ganglion in two human specimens in the basal, middle and upper middle
      turns were pooled for morphometric analysis of the cell area, nuclear area and
      axon diameter. Analysis of variance, bivariate scatter plots and multivariate
      cluster analysis provided evidence for 3 types of ganglion cells in the human
      spiral ganglion: large, intermediate and small, varying from each other
      significantly on the basis of cell area. It was suggested, based on the
      morphologic findings and prevalence of the cell types, that the large and
      intermediate cells were subtypes of the classic type I spiral ganglion cell,
      whereas the small ganglion cell was consistent with the classically described
      type II ganglion cell.

PMID- 8735074
TI  - Effect of contralateral acoustic stimulation on the growth of click-evoked
      otoacoustic emissions in humans.
AB  - Input-output (I/O) functions of click-evoked otoacoustic emissions (CEOAEs) were
      obtained over a 12 dB range for 64 normally hearing adult listeners with and
      without contralateral broadband noise (BBN). Contralateral acoustic stimulation
      (CAS) is a convenient way of suppressing responses to ipsilateral stimuli,
      probably acting via the medial olivocochlear system (MOCS). The present study
      shows that this contralateral sound suppression of CEOAEs is largest at low
      stimulus levels. In fact, the curves obtained under CAS approach the curves
      obtained without CAS as stimulus level rises. I/O slope analysis for the whole
      study population (n = 64) showed a slight but significant rise in slope with BBN,
      which may be interpreted as I/O function decompression. A loss of contralateral
      suppression effect at high ipsilateral stimulus levels was found in both very low
      and very high amplitude CEOAE subjects, despite the fact that I/O slopes differed
      between these two groups, whereas rise in slope under contralateral stimulation
      failed to be found for these same 2 groups of 16 subjects each. These findings
      clearly indicate that the MOCS is mostly functional at low sound levels, and
      suggest that the study of CEOAE I/O slope alteration under CAS may help specify
      one form of MOCS action on cochlear functioning.

PMID- 8735075
TI  - The binding site on cochlear stereocilia for antisera raised against renal Na+
      channels is blocked by amiloride and dihydrostreptomycin.
AB  - The mechanoelectrical transduction channels on hair cells have been suggested to
      be operated by tip links that are stretched when the hair bundle is deflected in
      the direction of the tallest row of stereocilia. Localising these channels is
      therefore an important test of this hypothesis. The transduction channels are
      known to be amiloride-sensitive and immunogold labelling with antibodies raised
      against the amiloride-sensitive epithelial Na+ channel from kidney (alpha NaCh),
      has suggested that sites with similar characteristics are located in the region
      where the tips of the shorter stereocilia appear to come into contact with the
      sides of the adjacent taller stereocilia rather than being associated directly
      with the tip links. Now, further immunocytochemical experiments have been
      performed to determine if amiloride and dihydrostreptomycin, both of which can
      block transduction, can affect this labelling. Immunofluorescent labelling of the
      stereocilia is obtained when surface preparations of the organ of Corti are fixed
      and incubated with alpha NaCh followed by an appropriate secondary antibody. This
      labelling is abolished by trypsinization prior to fixation but retained if the
      tissue is pretreated with amiloride and then trypsinized in its presence. Because
      amiloride is known to protect amiloride-binding sites from degradation by
      trypsin, these results suggest that alpha NaCh is revealing amiloride-binding
      sites on the stereocilia. Similarly, immunofluorescent labelling of the
      stereocilia is abolished if cochlear tissue is pretreated with
      dihydrostreptomycin (DHS) and fixed in its presence prior to incubation with
      alpha NaCh. Quantitative analysis of colloidal gold labelling using transmission
      electron microscopy shows that DHS treatment produces a significant reduction in
      the number of gold particles on stereocilia, especially in the region of contact
      between them. These results suggest that anti-Na+ recognises a site with
      characteristics similar to the mechanoelectrical transduction channels.

PMID- 8735076
TI  - Basic fibroblast growth factor (FGF-2) affects development of acoustico
      vestibular neurons in the chick embryo brain in vitro.
AB  - The effects of basic fibroblast growth factor (FGF-2) on presumptive auditory and
      vestibular neurons from the medulla were studied in primary cell cultures. The
      part of the rhombic lip that forms nucleus magnocellularis (homologue of the
      mammalian anteroventral cochlear nucleus) was explanted from white leghorn
      chicken embryos at Hamburger-Hamilton stage 28 (E5.5), the time when precursors
      of the magnocellularis bushy cells migrate and begin to differentiate in situ. In
      vitro the neuroblasts migrated onto 2-D substrates of purified collagen,
      differentiated, and expressed neuronal markers. One-half of the cultures were
      supplemented with human recombinant FGF-2 (10 ng/ml daily) for 5-7 days; the
      others, with fetal bovine serum. FGF-2 more than doubled the length of neurite
      outgrowth during the first 3 day treatment compared to serum, but the number of
      migrating neuroblasts was unaffected. Although neurites attained greater lengths
      in FGF-2, they usually degenerated after 4-5 days; in serum their growth
      continued for several weeks. Differentiation of neuronal structure, including
      axons and dendrites, began within 1-2 days in bFGF but required at least 5-7 days
      in serum. Histochemical observations in vitro and in situ with antibodies to FGF
      receptor demonstrated immunopositive patches on acoustico-vestibular neuroblasts
      at stage 28, when they are migrating and first forming their axons. The findings
      suggest that FGF-2 stimulates neurite outgrowth in the cochlear and vestibular
      nuclei. FGF-2 may accelerate cell death by overstimulating neuroblasts, but other
      factors are needed to sustain their further development.

PMID- 8735077
TI  - The topographical organization of descending projections from the central nucleus
      of the inferior colliculus in guinea pig.
AB  - We describe the descending projections from the central nucleus of the inferior
      colliculus (CNIC) in guinea pig. Focal injections of the tracer biocytin, made in
      physiologically defined frequency regions of the CNIC, labelled laminated axonal
      terminal fields in the ipsilateral dorsal nucleus of the lateral lemniscus, and
      bilaterally in the ventral nucleus of the trapezoid body and the dorsal cochlear
      nucleus. Labelling was also present in the rostral periolivary nucleus, but we
      could not distinguish a clear border between the terminal fields in this nucleus
      and those in the ventral nucleus of the trapezoid body. Labelling observed in the
      ventral nucleus of the lateral lemniscus, and to a lesser extent in the dorsal
      nucleus of the lateral lemniscus, was accompanied by retrogradely labelled somata
      and therefore we cannot conclude unequivocally that the CNIC projects to these
      lemniscal nuclei. Where the labelling was ordered topographically, its position
      varied as a function of the best frequency at the injection site. High-frequency
      regions in the CNIC project to the medial parts of the ventral nucleus of the
      trapezoid body and dorsal cochlear nucleus, while low-frequency regions in the
      CNIC project to the lateral parts of the ventral nucleus of the trapezoid body
      and dorsal cochlear nucleus. Additional axonal labelling with terminal boutons,
      but with no apparent topographical arrangement, was present in the ipsilateral
      horizontal cell group, sagulum, and also bilaterally in the superficial granule
      cell layer of the ventral cochlear nucleus and layer 2 of the dorsal cochlear
      nucleus. Our findings are consistent with the existence of tonotopically
      organised feedback projections from the CNIC to the brainstem nuclei that project
      to it.

PMID- 8735078
TI  - Genetics of age-related hearing loss in mice. III. Susceptibility of inbred and
      F1 hybrid strains to noise-induced hearing loss.
AB  - Some humans and mice are genetically predisposed to age-related hearing loss
      (AHL), and others are variously susceptible to noise-induced hearing loss (NIHL).
      The inbred C57BL/6J (B6) mice exhibit AHL at an early age, whereas the inbred
      CBA/CaJ (CB) mice do not. The B6 mice are much more susceptible to NIHL than are
      the CB mice (Shone et al., 1991; Li, 1992a). The B6 mice possess an Ahl gene
      which maps to chromosome 10 (Erway et al., 1995). This study was designed, using
      these two inbred strains plus two F1 hybrid strains of mice, to begin to test the
      hypothesis that the Ahl genotypes may influence the susceptibility to NIHL. These
      strains of mice (with putative genotypes) are: inbred CB (+/+) and B6 (Ahl/Ahl);
      hybrid CBB6F1 (+/Ahl) and B6D2F1 (Ahl/Ahl; D2 represents inbred DBA/2J). Twenty
      four mice of each of these four strains were exposed to noise (110 dB for 0, 1 or
      2 h) and tested for auditory-evoked brainstem response (ABR) thresholds. The CB
      and CBB6F1 strains of mice did not differ significantly from each other,
      exhibiting mostly temporary threshold shifts. The B6 and B6D2F1 strains of mice
      did not differ significantly from each other, but did exhibit permanent threshold
      shifts. These results support the hypothesis that genetic predisposition to AHL
      may be revealed at a younger age by NIHL. This suggests that it may be possible
      to use the NIHL to distinguish segregating genotypes (+/Ahl vs. Ahl/Ahl) among
      backcross progeny and thereby to identify and map single genes for AHL.

PMID- 8735079
TI  - Recommendation to include OspA and OspB in the new immunoblotting criteria for
      serodiagnosis of Lyme disease.
AB  - In October 1994, the Second National Conference on the Serologic Diagnosis of
      Lyme Disease recommended a two-step approach to serological testing. The first
      step was the performance of an enzyme-linked immunosorbent assay (ELISA); the
      second step was a confirmatory immunoblot. New criteria for the interpretation of
      a positive immunoblot were also recommended. The committee decided to omit the 31
      and 34-kDa bands (OspA and OspB, respectively) from the choice of bands
      considered diagnostic for a positive immunoblot. Since we had previously included
      these in our diagnostic criteria for Lyme disease-positive immunoblots, we
      reviewed data for all patients attending a Lyme disease center with positive
      ELISAs and immunoblot assays for Lyme disease from 1 September 1992 to 31
      December 1993. The criteria for a positive Western blot (immunoblot) were the
      presence of 5 or 12 bands, including the 10 recommended by the conference, and
      the presence of the 31- and 34-kDa protein bands. Of the 136 patients evaluated,
      50 were considered to have Lyme disease. Of these 50, 4 (8%) would not have met
      immunoblot criteria for the diagnosis if the new recommendations were used. Had
      the 31- and 34-kDa bands been included as part of the diagnostic requirements for
      immunoblot, these patients would have been included. Although overdiagnosis of
      Lyme disease appears to be the more frequent problem, our concern is that the
      exclusion of the 31- and 34-kDa protein bands from the diagnostic criteria may
      result in the underdiagnosis of Lyme disease by those who would rely too heavily
      on serological confirmation. The addition of the 31- and 34-kDa bands to those
      recommended for confirmatory immunoblot should be reconsidered.

PMID- 8735080
TI  - Detection of Bordetella pertussis by rapid-cycle PCR and colorimetric microwell
      hybridization.
AB  - The use of rapid-cycle PCR combined with colorimetric microwell hybridization for
      detecting Bordetella pertussis was investigated. Rapid cycling was performed with
      an air thermocycler (model 1605; Idaho Technology, Idaho Falls, Idaho). Although
      the instrument was originally designed to be used with capillary tubes, an
      adapter that allows this instrument to be used with PCR tubes has recently been
      introduced. Because of the low heat capacity of air, the thermocycler has rapid
      transition rates between temperatures. The combination of a rapid temperature
      transition rate, small sample volume (10 microliters), and overshooting or
      undershooting of the temperature set points allowed the cycles to be reduced to 5
      s for denaturation and 10 s for extension and annealing. Thus, the amplification
      could be completed in a total of approximately 35 min. Amplified DNA was detected
      with biotin-labeled primers and by hybridization to a capture probe immobilized
      in microwell plates. When simulated clinical specimens consisting of pooled
      nasopharyngeal washes with known numbers of B. pertussis organisms were examined
      by this procedure, as little as one organism per 5 microliters of sample could be
      detected. Six nasopharyngeal aspirates or washes from culture-positive patients
      were positive by PCR, as were two of seven specimens obtained from patients that
      were negative by culture and direct fluorescent-antibody assay. The two patients
      who were PCR positive but culture and direct fluorescent-antibody assay negative
      had clinical disease compatible with pertussis. This method appears to be a
      sensitive, convenient means of detecting B. pertussis in clinical specimens. The
      total time required for specimen processing, amplification, and detection is
      about 2.5 h.

PMID- 8735081
TI  - Detection of Borrelia burgdorferi-specific DNA in urine specimens from patients
      with erythema migrans before and after antibiotic therapy.
AB  - A nested PCR was developed for the detection of Borrelia burgdorferi-specific DNA
      in the urine of patients with erythema migrans. The target for the nested PCR was
      a specific region of the flagellin gene; the detection limit was less than five
      organisms of B. burgdorferi including all three species B. burgdorferi sensu
      stricto, B. afzelii, and B. garinii. A prospective, controlled, blinded study was
      performed with 26 patients with erythema migrans to evaluate the nested PCR
      method with clinical samples. B. burgdorferi-specific DNA could be detected in
      urine specimens from 22 of 24 patients with erythema migrans (sensitivity,
      91.61%). Immediately after therapy, 11 of 19 patients still yielded positive
      results (58%). Eight weeks after therapy, 2 of 16 patients (13%) were positive by
      PCR of urine, and 20 weeks after treatment none of seven investigated urine
      samples was reactive. Essential for the sensitivity that was obtained was the
      development of a simple DNA extraction procedure. The results of the study
      indicate that the described method is highly sensitive and allows for the
      effective control of the efficacy of antibiotic therapy in patients with early
      Lyme borreliosis.

PMID- 8735082
TI  - Genomic fingerprinting for epidemiological differentiation of Staphylococcus
      aureus clinical isolates.
AB  - We used genomic fingerprinting to investigate an outbreak of methicillin
      resistant Staphylococcus aureus in the neonatal intensive care units (NICUs) of
      two hospitals. The hospitals are located in the same city and are part of the
      same medical care system. Fingerprinting was done by Southern blot hybridization
      with DNA probes for the genes encoding the S. aureus collagen adhesin (cna),
      fibronectin-binding proteins (fnbA and fnbB), and beta-toxin (hlb). Genomic DNA
      was digested with HaeIII (cna and fnbA-fnbB probes) or HindIII (hlb probe).
      Hybridization patterns could be distinguished on the basis of (i) the presence or
      absence of cna, (ii) the size of the restriction fragment containing the cna
      gene, (iii) restriction fragment length polymorphisms within fnbA and fnbB, (iv)
      the presence of a lysogenic phage within hlb, and (v) the sizes of the
      restriction fragments containing the phage-bacterial DNA junction fragments. Over
      a period of 4 months we examined a total of 46 isolates obtained from various
      wards within each hospital. Among these 46 isolates, we observed a total of 4 cna
      patterns, 11 fnbA-fnbB patterns, and 11 hlb patterns. Southern blots with HaeIII
      digested genomic DNA and a combination of all three gene probes revealed a total
      of 16 clearly distinguishable patterns. A total of 22 of the 46 isolates were
      identical with respect to every genomic marker examined. A total of 21 of these
      22 isolates were obtained from patients within an NICU. Nineteen of 21 isolates
      also exhibited identical antibiotic resistance profiles (antibiogram). Although 5
      of the remaining 24 strains exhibited an antibiogram identical to those of the
      NICU isolates, all 24 strains could be distinguished from the NICU isolates by at
      least one genomic marker. These results suggest that the NICU isolates had a
      common origin and that genomic fingerprinting with the cna, fnbA, fnbB, and hlb
      gene probes can provide an important epidemiological tool for the identification
      of clinical isolates of S. aureus.

PMID- 8735083
TI  - Molecular typing of Salmonella typhi strains from Dhaka (Bangladesh) and
      development of DNA probes identifying plasmid-encoded multidrug-resistant
      isolates.
AB  - Seventy-eight Salmonella typhi strains isolated in 1994 and 1995 from patients
      living in Dhaka, Bangladesh, were subjected to phage typing, ribotyping, IS200
      fingerprinting, and PCR fingerprinting. The collection displayed a high degree of
      genetic homogeneity, because restricted numbers of phage types and DNA
      fingerprints were observed. A significant number of the S. typhi strains (67%)
      were demonstrated to be multiple drug resistant (MDR). The vast majority of the
      MDR strains were resistant to chloramphenicol, ampicillin, trimethoprim,
      streptomycin, sulfamethoxazole, and tetracycline (R type CATmSSuT), a resistance
      phenotype that has also frequently been observed in India. Only two strains
      displayed a distinct MDR phenotype, R type AT-mSSuT. Pulsed-field gel
      electrophoresis demonstrated the presence of large plasmids exclusively in the
      MDR strains of both R types. The plasmids present in the S. typhi strains of R
      type CATmSSuT could be conjugated to Escherichia coli and resulted in the
      complete transfer of the MDR phenotype. PCR fingerprinting allowed discrimination
      of MDR and susceptible strains. The DNA fragments enabling discrimination of MDR
      and susceptible S. typhi strains by PCR were useful genetic markers for
      identifying MDR encoded by large plasmids of the H1 incompatibility group.

PMID- 8735085
TI  - Rapid susceptibility testing for nontuberculosis mycobacteria using flow
      cytometry.
AB  - We demonstrated previously that susceptibility testing of Mycobacterium
      tuberculosis could be accomplished within 24 h after the organisms were incubated
      with antituberculosis agents by using fluorescein diacetate (FDA) staining and
      flow cytometry. Continued studies have now shown that assay suspensions
      containing M. avium, M. fortuitum, M. gordonae, or M. marinum incubated with
      various concentrations of ciprofloxacin, clarithromycin, erythromycin, kanamycin,
      rifampin, tobramycin hydrolyzed less FDA than drug-free controls. Suspensions of
      treated and nontreated mycobacteria could be easily differentiated at 6 and 24 h
      after the initiation of the susceptibility assays by using FDA staining and flow
      cytometry. In addition, multiplication of the mycobacteria was not required to
      discern differences between drug-free suspensions of mycobacteria and those
      treated with antimycobacterial agents. The flow cytometric assay is simple,
      reproducible, and rapid.

PMID- 8735084
TI  - Genetic identification of cryptic genospecies of Haemophilus causing urogenital
      and neonatal infections by PCR using specific primers targeting genes coding for
      16S rRNA.
AB  - Previous genetic analysis of Haemophilus influenzae strains isolated from genital
      and neonatal infections identified a group of biotype IV that constitutes a
      cryptic genospecies only distantly related to H. influenzae and H. Haemolyticus.
      Small-subunit rRNA genes of two representative strains of this genital
      Haemophilus genospecies (strains 16N and 2406) were sequenced. The analysis
      indicated that these strains form a monophyletic unit with H. haemolyticus and H.
      influenzae biogroups Influenzae and Aegyptius and are more closely related to H.
      haemolyticus than to H. influenzae biogroups Influenzae and Aegyptius. 16S rRNA
      gene sequences were used to formulate primers for PCR-based identification of
      cryptic genital Haemophilus organisms. A 242-bp fragment was amplified from
      strains belonging to the genital Haemophilus genospecies but not from strains of
      12 other Haemophilus species, including strains of H. influenzae biotype IV sensu
      stricto.

PMID- 8735086
TI  - Serodiagnosis of listeriosis based upon detection of antibodies against
      recombinant truncated forms of listeriolysin O.
AB  - Amino-terminal fragments of listeriolysin O (LLO) of 240 and 411 residues
      (fragments LLO240 and LLO411, respectively) were expressed in Escherichia coli as
      fusion polypeptides with maltose-binding protein (MBP) with the aim of producing
      specific antigens for use in serological tests. In Western blots (immunoblots)
      with crude bacterial extracts of the fusion polypeptides, the reactivities of MBP
      LLO240 and MBP-LLO411 with anti-LLO antibody (ALLO)- and anti-streptolysin O
      antibody (ASLO)-positive human sera were first compared with that of the entire
      LLO (LLO530) also fused to MBP (MBP-LLO530). Sixteen of 17 (94.1%) ALLO-positive
      samples reacting with MBP-LLO530 also reacted with MBP-LLO411, whereas this
      proportion dropped to 11 of 17 (64.7%) with MBP-LLO240. Alternatively, 18 of 19
      (94.7%) ASLO-positive samples giving an interpretable result reacted with MBP
      LLO530, whereas 1 of 19 (5.3%) of these samples reacted with MBP-LLO240 or MBP
      LLO411. The fusion polypeptide MBP-LLO411 was purified by maltose affinity
      chromatography and was further evaluated as a diagnostic antigen in a Western
      blot assay. Twenty-one of 21 (100%) serum samples obtained from patients with
      listeriosis and found to be positive for ALLO by a reference dot blot test
      reacted with MBP-LLO411, whereas 1 of 20 (5%) ASLO-positive serum samples and 1
      of 100 (1%) serum samples from healthy adults were reactive. Thus, a polypeptide
      limited to the 411 amino-terminal residues of LLO is a specific and sensitive
      antigen for the detection of ALLO.

PMID- 8735087
TI  - Diagnosis of Chlamydia trachomatis infections in asymptomatic men and women by
      PCR assay.
AB  - A PCR assay was evaluated for its ability to detect genital chlamydial infection
      in asymptomatic men and women. Urethral swab specimens were collected from 472
      men for culture and PCR assay, and first-void urine (FVU) specimens were
      collected from 379 of these men for enzyme immunoassay (EIA) and PCR assay.
      Cervical swab specimens were collected from 242 women for culture, EIA, and PCR
      assay. Patients were considered infected if they were culture positive or
      positive by PCR with both plasmid- and major outer membrane protein-based
      primers. By using this extended "gold standard," the prevalence of infection in
      this population was 7.6% for men and 7.9% for women. For men, the sensitivities
      of urethral swab specimen culture and PCR and FVU specimen EIA and PCR were 61,
      72, 55, and 91%, respectively. All assays had specificities of > or = 99.8%. The
      positive and negative predictive values for PCR testing of FVU specimens were 100
      and 99.4%, respectively, compared with values of 96.3 and 97.8%, respectively,
      for PCR of urethral swab specimens. The sensitivities of cervical swab specimen
      culture and PCR testing were 42 and 90%, respectively, with corresponding
      specificities of 100 and 99.3%. All cervical swabs were negative by EIA.
      Molecular techniques such as PCR assays are valuable tools for the detection of
      symptomatic genital chlamydial infection. In particular, PCR assays of FVU
      specimens from men offer a highly sensitive, noninvasive screening tool that will
      likely improve patient compliance for diagnostic testing.

PMID- 8735088
TI  - Diagnosis by AMPLICOR PCR of Chlamydia trachomatis infection in urine samples
      from women and men attending sexually transmitted disease clinics.
AB  - Screening of urine specimens from men for Chlamydia trachomatis infection by a
      commercial PCR assay (AMPLICOR C. trachomatis Test; Roche Diagnostic Systems,
      Inc., Branchburg, N.J.) is a sensitive and specific noninvasive diagnostic assay.
      Since screening of women for C. trachomatis infection with the AMPLICOR C.
      trachomatis Test has been limited to use with endocervical swab specimens, we
      conducted an evaluation of the AMPLICOR C. trachomatis Test for the detection of
      C. trachomatis using female urine samples and compared the results of those
      obtained by in vitro culture and PCR of endocervical swab specimens. For 713 men
      we compared the performance of AMPLICOR C. trachomatis Test with urine specimens
      with that of culture of urethral specimens. For specimens that were PCR positive
      and culture negative, two additional tests were used to resolve the
      discrepancies: direct fluorescent-antibody assay (DFA) of sediment from a spun
      endocervical specimen culture vial and major outer membrane protein-based PCR of
      the sediment from the endocervical specimen culture vial. Of 525 urine specimens
      from females, 67 (12.8%) were PCR positive, and 41 (7.8%) endocervical specimens
      from the 525 women were culture positive. After resolution of the discrepancies,
      the resolved sensitivity of the urine PCR was 93.3%, whereas the sensitivity of
      endocervical swab specimen culture was 67.3%. Of 468 female endocervical swab
      specimens, 47 (10.0%) had a positive PCR result and 33 (7.0%) were culture
      positive. The resolved sensitivity of the endocervical swab specimen PCR was 86%.
      Of 415 matched female urine and endocervical swab specimens, there were 49
      confirmed infections; 30 (61.2%) specimens were positive by culture of the
      endocervical swab specimen, 40 (81.6%) were positive by confirmed endocervical
      swab specimen PCR, 43 (87.8%) were positive by confirmed urine PCR, and all 49
      (100%) were positive by either endocervical swab specimen PCR or urine PCR. For
      men, the resolved sensitivity of the urine PCR was 88%, and the sensitivity of
      culture was only 50.7%. These results indicate that urine PCR is highly sensitive
      for the detection of C. trachomatis in both women and men and provides a
      noninvasive technique for routine screening for chlamydial infection.

PMID- 8735089
TI  - Utility of PCR in diagnosing pulmonary tuberculosis.
AB  - At present, the rapid diagnosis of pulmonary tuberculosis rests with microscopy.
      However, this technique is insensitive and many cases of pulmonary tuberculosis
      cannot be initially confirmed. Nucleic acid amplification techniques are
      extremely sensitive, but when they are applied to tuberculosis diagnosis, they
      have given variable results. Investigators at six centers in Europe compared a
      standardized PCR system (Amplicor; Roche) against conventional culture methods.
      Defined clinical information was collected. Discrepant samples were retested, and
      inhibition assays and backup amplification with a separate primer pair were
      performed. Mycobacterium tuberculosis complex organisms were recovered from 654
      (9.1%) of 7,194 samples and 293 (7.8%) of 3,738 patients. Four hundred fifty-two
      of the M. tuberculosis isolates from 204 patients were smear positive and culture
      positive. Among the culture-positive specimens, PCR had a sensitivity of 91.4%
      for smear-positive specimens and 60.9% for smear-negative specimens, with a
      specificity of 96.1%. Analysis of 254 PCR-positive, culture-negative specimens
      with discrepant results revealed that 130 were from patients with recently
      diagnosed tuberculosis and 94 represented a presumed laboratory error. Similar
      analysis of 118 PCR-negative, culture-positive specimens demonstrated that 27
      discrepancies were due to presumed uneven aliquot distribution and 11 were due to
      presumed laboratory error; PCR inhibitors were detected in 8 specimens. Amplicor
      enables laboratories with little previous experience with nucleic acid
      amplification to perform PCR. Disease in more than 60% of the patients with
      tuberculosis with smear-negative, culture-positive specimens can be diagnosed at
      the time of admission, and potentially all patients with smear-positive specimens
      can immediately be confirmed as being infected with M. tuberculosis, leading to
      improved clinical management.

PMID- 8735091
TI  - Evaluation of immunochromatographic assay systems for rapid detection of
      hepatitis B surface antigen and antibody, Dainascreen HBsAg and Dainascreen
      Ausab.
AB  - We evaluated two immunochromatographic assays (ICAs), Dainascreen HBsAg for
      detecting human hepatitis hepatitis B surface antigen (HBsAg) and Dainascreen
      Ausab for detecting human hepatitis B surface antibody (anti-HBs) in human serum.
      The ICA systems are composed of a comb-shaped device that contains nitrocellulose
      strips on which complexes of HBsAg and anti-HBs can be visualized. The results
      can be read within 15 min of incubation. The limit of detection for HBsAg was 3.1
      ng/ml and that for anti-HBs was 42 mIU/ml. Results of HBsAg detection agreed
      completely with those of conventional enzyme immunoassays (EIAs) and showed a
      100% sensitivity (158 of 158 samples) and a 100% specificity (304 of 304
      samples). The Dainascreen Ausab detected 184 of the 199 EIA-positive samples
      (sensitivity, 92.5%) and yielded 6 positive results among the 281 EIA-negative
      samples (specificity, 97.9%). The ICA systems are rapid and sensitive methods for
      detecting HBsAg and anti-HBs. They are low-cost systems that need no complex
      instrumentation for analysis and can be recommended for routine use in clinical
      microbiology laboratories.

PMID- 8735090
TI  - Flow cytometric immunofluorescence assay for detection of antibodies to human
      immunodeficiency virus type 1 using insoluble precursor forms of recombinant
      polyproteins as carriers and antigens.
AB  - A new serological assay, the recombinant flow cytometric immunofluorescence assay
      (r-FIFA), was developed for the early detection of human immunodeficiency virus
      type 1 (HIV-1) antibodies by using recombinant insoluble forms of HIV-1 Gag-p45,
      Gag-gp41 chimeric protein, gp160, Po197 polyprotein as antigens and autologous
      carriers through flow cytometry. These recombinant proteins were expressed in
      insect cells by a baculovirus expression system. Eight anti-HIV-1 seroconversion
      panels, a low-titer anti-HIV-1 panel from Boston Biomedica Inc. (BBI), and three
      HIV-1 seroconversion specimens from the Provincial Health Laboratory of Ontario,
      Toronto, Ontario, Canada (PHL), were tested and analyzed by r-FIFA. In
      sensitivity comparisons between r-FIFA and tests licensed by the U.S. Food and
      Drug Administration, which were used to test all of the HIV-1 panels from BBI,
      detection of HIV-1 antibody by r-FIFA was on average greater than 20 days earlier
      than that by enzyme immunoassay. The sensitivity of r-FIFA has permitted the
      detection of HIV-1-specific immunoglobulin G (IgG), IgM, and IgA antibodies
      during seroconversion. A kinetic analysis of HIV-1 antibody production of r-FIFA
      has shown that either IgG or IgM, or both, can be detected, depending on the
      phase and type of the immune response in the HIV-1-infected individual. Both
      primary and secondary immune responses were observed during this period. The r
      FIFA results suggest that implementation of r-FIFA may significantly reduce the
      "window" period from the time of infection to the time of seroconversion, with
      earlier detection of antibodies after initial infection. This would also make it
      possible for us to understand the immune response and the precise mechanisms of
      immunopathogenesis in the early period of HIV-1 infection.

PMID- 8735092
TI  - Serological diagnosis of bovine neosporosis by Neospora caninum monoclonal
      antibody-based competitive inhibition enzyme-linked immunosorbent assay.
AB  - Neospora caninum, a protozoan parasite closely related to Toxoplasma gondii,
      causes abortion and congenital infection in cattle. To investigate specific
      methods of antemortem diagnosis, the antibody responses of infected cows were
      evaluated by immunoblot assay and competitive inhibition enzyme-linked
      immunosorbent assay (CI-ELISA) by using a monoclonal antibody (MAb), MAb 4A4-2,
      against N. caninum tachyzoites. MAb 4A4-2 bound diffusely to the exterior surface
      of N. caninum tachyzoites and recognized a single 65-kDa band in immunoblots. MAb
      4A4-2 was unreactive to antigens of two closely related apicomplexan protozoa,
      Toxoplasma gondii and Sarcocystis cruzi. Binding of MAb 4A4-2 was inhibited by
      mild periodate treatment of N. caninum antigen, demonstrating the carbohydrate
      nature of the epitope. Immunoblot analysis of N. caninum tachyzoite antigens with
      sera from cows with confirmed Neospora-induced abortion revealed at minimum 14
      major antigens ranging from 11 to 175 kDa. Although the recognized antigens
      varied from cow to cow, antigens of 116, 65, and 25 kDa were detected in all cows
      with abortion confirmed to be caused by N. caninum. The binding of MAb 4A4-2 to
      N. caninum tachyzoite antigen was consistently inhibited by sera from Neospora
      infected cows in a CI-ELISA format and was not inhibited by sera from Neospora
      antibody-negative cows. Furthermore, sera from cattle experimentally infected
      with T. gondii, S. cruzi, Sarcocystis hominis, or Sarcocystis hirsuta, which had
      cross-reactive antibodies recognizing multiple N. caninum antigens by immunoblot
      assay, did not inhibit binding of MAb 4A4-2 in the CI-ELISA. Thus, MAb 4A4-2
      binds a carbohydrate epitope on a single N. caninum tachyzoite surface antigen
      that is recognized consistently and specifically by Neospora-infected cattle.

PMID- 8735093
TI  - Isolation of Ehrlichia canis from dogs following subcutaneous inoculation.
AB  - Subcutaneous inoculation of dogs with Ehrlichia canis was investigated as a more
      appropriate model of canine ehrlichiosis, which is naturally transmitted by
      arthropod vectors. A dose-dependent response occurred following subcutaneous
      inoculation of seven groups of dogs with log concentrations of E. canis-infected
      canine-origin cells. Ehrlichial infection in dogs was defined as concurrence of
      an increased titer of anti-E. canis immunoglobulin G (IgG) antibody in serum, a
      decreased platelet concentration, and isolation of E. canis by blood culture. In
      dogs administered the two lowest doses, no changes were detected. In seven of
      nine dogs administered three intermediate doses, the only change detected was a
      transient and mild increase in the anti-E. canis IgG antibody titer in serum.
      Only two of nine dogs inoculated with the intermediate doses developed an
      ehrlichial infection. Five of six dogs administered the two highest dose of E.
      canis developed an ehrlichial infection. These dogs had the highest IgG antibody
      titers in serum and the earliest isolation of E. canis from blood. In dogs that
      developed an ehrlichial infection, thrombocytopenia occurred by 28 days after
      inoculation, while increased IgG antibody titers in serum and blood cultures
      positive for E. canis occurred as early as 14 days postinoculation.
      Thrombocytopenia and seroconversion occurred later in the course of infection
      than previously reported for ehrlichial infections induced by intravenous
      inoculation. The route of administration and E. canis inoculum size can influence
      the course of ehrlichial infection and should be regarded as important variables
      in experimentally induced canine ehrlichiosis.

PMID- 8735094
TI  - Murine model of invasive pulmonary aspergillosis following an earlier stage,
      noninvasive Aspergillus infection.
AB  - Aspergillus spp. occasionally cause invasive pulmonary aspergillosis following
      noninvasive infection in patients with underlying bronchopulmonary disorders
      regardless of their systemic immunological conditions. We developed a murine
      model of invasive pulmonary aspergillosis following an earlier stage, noninvasive
      Aspergillus infection. BALB/c mice were inoculated intratracheally with agarose
      beads containing Aspergillus fumigatus conidia. Two weeks after inoculation, half
      of the mice were immunosuppressed with cortisone acetate. During a 4-week
      observation period, the survival rate of infected immunosuppressed mice was
      significantly lower (P < 0.01) than that of infected nonimmunosuppressed mice.
      The number of CFU in the lungs gradually decreased in the nonimmunosuppressed
      mice, whereas a time-related significant increase (P < 0.05) of CFU was
      demonstrated in the immunosuppressed mice. In the lungs of the
      nonimmunosuppressed mice, there was marked accumulation of neutrophils,
      lymphocytes, and macrophages (in this order) around the agarose beads in the
      bronchi. Aspergillus hyphae were surrounded by the inflammatory cells and did not
      invade the lung parenchyma. In contrast, in the immunosuppressed mice,
      Aspergillus hyphae proliferated markedly and invaded the lung parenchyma after
      immunosuppression. In this model, the two-dimensional extents of the lesions were
      also evaluated with an image-processing system. Time-related increase of the area
      of peribronchial necrotic lesions was significant (P < 0.05) after
      immunosuppression. This model should therefore be useful for investigating the
      pathophysiology of noninvasive Aspergillus infection and invasive pulmonary
      aspergillosis and also for clarifying the mechanism of conversion to the invasive
      disease from the noninvasive stage.

PMID- 8735095
TI  - Quantitative detection of human immunodeficiency virus (HIV) antigen by the
      Enzymun-Test: comparison with alternative assays and nucleic acid sequence-based
      amplification of HIV type 1 RNA.
AB  - A new modular automated enzyme immunoassay (EIA) (Enzymun-Test HIV Ag: Boehringer
      Mannheim) for quantitative human immunodeficiency virus (HIV) antigen detection
      was evaluated by testing a panel of 1,506 serum samples, including
      seroconversions, dilution series, follow-up samples from patients under
      antiretroviral therapy, single serum specimens from HIV-seropositive individuals
      in different stages of infection, potentially cross-reactive samples, and sera
      from HIV-negative hospitalized patients. The Abbott HIV type 1 (HIV-1) antigen
      monoclonal antibody assay served as the reference assay, and nucleic acid
      sequence-based amplification (Organon Teknika) for quantitative amplification of
      HIV-1 RNA was used for follow-up of patients under antiretroviral chemotherapy.
      The Boehringer Mannheim and Abbott EIAs showed concordant results for the early
      detection of HIV antigen in all the seroconversion panels. The follow-up samples
      from 29 HIV-infected individuals under antiretroviral therapy gave divergent
      results between both antigen tests. For the detection of HIV antigen in single
      serum samples from HIV-infected patients in different stages of HIV infection, a
      higher number of positive samples was detected with the Abbott HIV-1 antigen
      monoclonal antibody assay in samples from patients in stages II and III of HIV
      infection. The Enzymun-Test detected three or more positive samples than did the
      Abbott assay among the samples of patients with AIDS. The concordance on a sample
      to-sample basis between the Boehringer Mannheim and Abbott EIAs was 98.6%. The
      sensitivity of the Enzymun-Test in comparison to the reference assay was 97.2%;
      the specificity was 98.8%. Although no close correlation could be found between
      the amount of viral RNA in serum detected by nucleic acid sequence-based
      amplification and the concentration of HIV antigen, a high HIV-1 RNA copy number
      was mostly associated with high levels of HIV antigen. In conclusion, the Enzymun
      Test permits accurate HIV antigen detection and offers, in contrast to previous
      assays, the possibility of completely automated detection.

PMID- 8735096
TI  - Molecular epidemiology of impetiginous group A streptococcal infections in
      aboriginal communities of northern Australia.
AB  - Group A streptococcal infections among the Aboriginal communities of the Northern
      Territory of Australia are endemic, with a concurrently high rate of the
      postinfection sequelae of rheumatic fever and acute post-streptococcal
      glomerulonephritis. The majority of the group A streptococcal isolates from the
      Northern Territory are not typeable by M typing. We recently developed a novel
      genotyping method, Vir typing. A preliminary study using this method
      discriminated all the M-nontypeable (MNT) isolates. Vir typing is based on
      restriction fragment length polymorphisms of the 4- to 7-kb Vir regulon of group
      A streptococci, which contains a number of genes, including emm (the gene for M
      protein). A total of 407 isolates of group A streptococci obtained from four
      Aboriginal communities over a 4-year period were typed by this genotyping method.
      Forty-two distinct genotypes were found among the isolates, including 22 among
      the MNT isolates. The correlation between Vir type and M type was good. This
      genotyping method allows the characterization of all group A streptococcal
      isolates from Aboriginal communities in the Northern Territory. We also propose
      that Vir typing be used in conjunction with M typing for epidemiological
      surveillance in geographical regions where the majority of isolates are MNT.

PMID- 8735098
TI  - Detection of quinolone-resistant Neisseria gonorrhoeae.
AB  - The present National Committee for Clinical Laboratory Standards (NCCLS)
      guideline for testing Neisseria gonorrhoeae quinolone susceptibility defines only
      a susceptible category for ciprofloxacin, enoxacin, lomefloxacin, and ofloxacin,
      while susceptible, intermediate, and resistant categories are defined for
      fleroxacin. To further define the criteria for detection of quinolone resistance
      in gonococci, by standard disk diffusion and agar dilution methodologies
      recommended by the NCCLS, we tested 29 strains of quinolone-resistant N.
      gonorrhoeae (QRNG) recently isolated from ofloxacin-treated patients who were
      considered clinical failures. Regression analyses were performed on these results
      together with those of another 20 strains showing reduced susceptibility and 13
      fully susceptible strains (ofloxacin MICs of < or = 0.25 microgram/ml). With 5
      micrograms ofloxacin disks, resistance in 27 (93.1%) of the QRNG strains (MICs of
      > 1 microgram/ml) was detected by the criterion of a zone diameter of < 22 mm,
      while in the remaining 2 (6.9%), the disks failed to detect resistance. A cluster
      of 15 highly resistant strains showed ofloxacin MICs of > 4 micrograms/ml and
      zone diameters of < 13 mm. When tested with 5-micrograms ciprofloxacin disks, the
      corresponding values for resistance and high-level resistance of these QRNG
      strains were < 25 mm (MICs of > 0.5 micrograms/ml) and < 15 mm (MICs of > 2
      micrograms /ml), respectively. Six strains for which ofloxacin MICs were > or = 8
      micrograms/ml showed no zones at all with both 5-micrograms ofloxacin and 5
      micrograms ciprofloxacin disks. These QRNG strains are now firmly established in
      the Southeast Asia region, and it is important for clinical laboratories to
      recognize these clinically resistant strains and to monitor their spread.

PMID- 8735097
TI  - DNA fingerprinting of Vibrio cholerae strains with a novel insertion sequence
      element: a tool to identify epidemic strains.
AB  - A novel Vibrio cholerae insertion sequence element, designated IS1004, was
      characterized and used for DNA fingerprinting of Vibrio spp. IS1004 comprises 628
      bp and contains an open reading frame whose product shows a large degree of
      sequence identity with the IS200-encoded transposase. IS1004 was present in one
      to eight copies in most of the V. cholerae strains analyzed. The IS1004-generated
      fingerprints of epidemic V. cholerae strains with serotype O1 were closely
      related, although it was possible to distinguish between the two biotypes,
      classical and El Tor. Non-O1 serotype strains generally showed heterogeneous
      patterns unrelated to those of the epidemic O1 strains. Several strains were
      observed with identical or related fingerprint patterns but expressed different
      serotypes. Conversely, strains with different fingerprint patterns but identical
      serotypes were also found. These observations indicate that the gene clusters
      coding for distinct O antigens may be transferred horizontally between V.
      cholerae strains. Two examples of non-O1 strains with a fingerprint resembling
      that of epidemic O1 strains were found; they were the O139 Bengal strain and an
      O37 strain. The O139 Bengal strain is closely related to the El Tor biotype. The
      O37 strain was responsible for a large cholera outbreak in Sudan in 1968 and was
      classified as a noncholera vibrio. Our study, however, shows that the O37 Sudan
      strain is genetically closely related to classical O1 strains. Similar to O139
      Bengal, O37 Sudan lacked most of the O1 antigen cluster but did contain flanking
      genes. Thus, O37 Sudan represents a second example of an epidemic V. cholerae
      strain carrying non-O1 antigens. This study underlines the importance of
      genotypic methods for the differentiation of V. cholerae strains and for
      recognition of strains with epidemic potential.

PMID- 8735099
TI  - Detection of enteroviruses from clinical specimens by spin amplification shell
      vial culture and monoclonal antibody assay.
AB  - Conventional tube cell culture was compared with a 72-h, spin-amplified shell
      vial indirect immunofluorescence assay for the detection of enterovirus from
      clinical specimens. The sensitivity for the shell vial assay after resolution of
      discrepant results were 93 and 100%, respectively. The shell vial assay detected
      93% of the positive cultures within 72 h of incubation while conventional tube
      culture detected only 51% of the positive cultures within the same time interval.
      The data suggest that a spin-amplified shell vial indirect immunofluorescence
      assay may be useful for the detection of enterovirus from clinical specimens.

PMID- 8735100
TI  - Molecular subtyping of Neisseria meningitidis serogroup B: comparison of five
      methods.
AB  - In order to compare methods for subtyping Neisseria meningitidis serogroup B
      isolates, 96 isolates obtained from various locations in the United States and
      northwestern Europe were subtyped by five methods: monoclonal antibody (MAb)
      based serotyping and serosubtyping, DNA macrorestriction analysis by pulsed-field
      gel electrophoresis (PFGE), multilocus enzyme electrophoresis (MEE), ribotyping,
      and PCR-restriction fragment length polymorphism of the internally transcribed
      spacer region of the rRNA operon (ITS PCR-RFLP). All N. meningitidis serogroup B
      isolates were typeable by PFGE, MEE, ribotyping, and ITS PCR-RFLP. Only 44.8% of
      the isolates were completely typeable (both serotype and serosubtype
      determination) by MAb-based serotyping and serosubtyping. 60.4% of the isolates
      could be serotyped but not serosubtyped, and 90.6% of the isolates could be
      either serotyped or serosubtyped. Simpson's discrimination indices of diversity
      for the methods were as follows: PFGE, 99.7%; MEE, 99.4%; ribotyping, 98.8%; MAb
      serotyping, 75.8%; MAb serotyping and/or serosubtyping 97.5%; and ITS PCR-RFLP,
      84.2%. The high degree of diversity observed by PFGE, MEE, and ribotyping can be
      explained by the fact that isolates were collected from different geographic
      locations at various times. PFGE, MEE, and ribotyping showed greater
      discriminatory abilities than MAb-based serotyping and serosubtyping or ITS PCR
      RFLP.

PMID- 8735101
TI  - Molecular epidemiology of Enterobacter aerogenes acquisition: one-year
      prospective study in two intensive care units.
AB  - To evaluate the respective contributions of patient-to-patient transmission and
      endogenous acquisition of Enterobacter aerogenes isolates, we conducted a
      prospective epidemiologic study in two intensive care units (ICUs) between May
      1994 and April 1995. We collected a total of 185 E. aerogenes isolates: 130 from
      51 patients in a surgical ICU (SICU), 45 from 26 patients in a medical ICU
      (MICU), and 10 from the environments in these two ICUs. All isolates were typed
      by random amplification of polymorphic DNA and enterobacterial repetitive
      intergenic consensus PCR. Among the 175 clinical isolate, we observed 40
      different profiles by random amplification of polymorphic DNA and 36 different
      profiles by enterobacterial repetitive intergenic consensus PCR. We identified a
      ubiquitous and prevalent clone, corresponding to 58% of SICU and 41% of MICU
      clinical isolates. Three epidemiologically related strains were specific to each
      ICU and represented 17% of SICU and 24% of MICU clinical isolates; unique type
      strains represented 17 and 29% of SICU and MICU clinical isolates, respectively,
      and E. aerogenes strains which were spread to a limited degree and which were
      isolated less than five times during the 1-year study period represented 8 and 6%
      of SICU and MICU clinical isolates, respectively. Our results show that E.
      aerogenes is acquired in the ICU in three different ways: patient-to-patient
      spread of a prevalent or an epidemiologically related strain, acquisition de novo
      of a strain from patients' own flora, and acquisition of a nonendemic strain
      followed by occasional patient-to-patient transmission. The findings point out
      the importance of patient-to-patient transmission in E. aerogenes acquisition and
      suggest that changes in E. aerogenes ecology in the hospital have taken place
      during the past decade.

PMID- 8735102
TI  - Detection of equine infectious anemia viral RNA in plasma samples from recently
      infected and long-term inapparent carrier animals by PCR.
AB  - Control of equine infectious anemia (EIA) is currently based on detection of anti
      EIA virus (EIAV) antibodies. However, serologic diagnostic methods may give false
      negative results in infected horses that fail to respond adequately or are in the
      early stages of infection. We developed a reverse transcriptase nested PCR (RT
      nPCR) assay for the detection of viral gag gene sequences in plasma from EIAV
      infected horses. The ability of RT-nPCR to detect field strains of EIAV was
      investigated by assaying plasma samples from 71 horses stabled on EIA quarantine
      ranches. Positive PCR signals were detected in 63 of 63 horses with EIAV antibody
      test-positive histories on approved serologic tests, demonstrating that RT-nPCR
      was probably directed against highly conserved sequences in the viral genome. The
      RT-nPCR assay, agar gel immunodiffusion test, and conventional virus isolation
      were compared for detection of early infection in 12 experimentally infected
      ponies. Viral gag sequences were detected in all 12 animals by 3 days
      postinfection (p.i.) by RT-nPCR, whereas virus could not be routinely isolated on
      cell culture until 9 to 13 days p.i. and EIAV antibodies could not be detected by
      agar gel immunodiffusion until 20 to 23 days p.i. Finally, specificity of the RT
      nPCR assay was examined by testing plasma from 43 horses with serologic test
      negative histories and no known contact with EIAV-infected animals. Viral gag
      sequences were not detectable in this control group. These data suggest that the
      EIAV RT-nPCR assay effectively detects EIAV and is more sensitive than current
      standard methods for detection of early stages of infection.

PMID- 8735103
TI  - Antigenic variability among North American and European strains of porcine
      reproductive and respiratory syndrome virus as defined by monoclonal antibodies
      to the matrix protein.
AB  - Two hybridoma cell lines producing monoclonal antibodies (Mabs) to the 19-kDa
      matrix (M) protein of porcine reproductive and respiratory syndrome virus (PRRSV)
      were obtained from BALB/c mice that were immunized with a reference Quebec tissue
      culture-adapted strain (strain IAF-Klop). The polypeptide specificities of the
      MAbs were determined by immunoblotting and immunoprecipitation tests with
      concentrated and purified preparations of the virus and by determining their
      reactivities with the Escherichia coli-expressed gene products of open reading
      frames 5 to 7. The two anti-M protein MAbs (MAbs IAFK3 and IAFK6) and another MAb
      (MAb IAFK8) directed to the 15-kDa nucleocapsid (N) protein were devoid of virus
      neutralizing activity. A library of four anti-N protein MAbs (MAbs IAFK8, SDOW17,
      VO17, and EP147) and two anti-M protein MAbs (MAbs IAFK6 and IAFK3) was used to
      investigate, by an indirect fluorescent-antibody assay, the antigenic diversity
      of 15 Canadian PRRSV isolates, in comparison with those of the U.S. ATCC VR2332
      attenuated vaccine strain and two reference European (Lelystad and Weybridge)
      PRRSV strains. The North American and European PRRSV isolates tested shared the
      epitopes recognized by anti-N protein MAbs IAFK8 and SDOW17, but three distinct
      patterns could be identified on the basis of their reactivities with the other
      anti-PRRSV MAbs. No reactivity to the anti-M protein MAbs was observed by either
      European PRRSV isolate or the attenuated U.S. vaccine strain.

PMID- 8735104
TI  - Evaluation of pulsed-field gel electrophoresis as a typing system for Candida
      rugosa: comparison of karyotype and restriction fragment length polymorphisms.
AB  - Nosocomial infections with Candida species have emerged as an increasingly
      important cause of morbidity and mortality in intensive care units. Ten Candida
      rugosa isolates from a previously documented cluster of C. rugosa infections in
      one hospital (nine burn unit isolates and one isolate from another hospital ward)
      and eight C. rugosa isolates recovered in a referral fungus testing laboratory
      (comparison isolates) from distinct geographic areas were investigated by
      molecular techniques. Isolates were from multiple anatomic sites. Pulsed-field
      gel electrophoresis (PFGE) of whole-cell DNA was performed with the 18 C. rugosa
      isolates as a marker of strain identity. The PFGE karyotypes of the C. rugosa
      isolates were demonstrated from four to seven chromosome bands. Karyotyping
      revealed the same PFGE pattern for the nine outbreak isolates from the burn unit,
      confirming clonal strain transmission. The isolate from the other hospital ward
      had a distinct karyotype. Distinct PFGE karyotype patterns were demonstrated for
      the eight comparison isolates. Restriction fragment length polymorphisms (RFLP)
      generated from whole-cell DNA digested with SfiI demonstrated the same RFLP
      pattern among outbreak isolates. Among comparison isolates, karyotyping
      distinguished some isolates that were indistinguishable by RFLP patterns.
      Karyotyping by PFGE appears to be the most useful molecular typing tool for
      discrimination among strains of C. rugosa and will be a useful marker for
      evaluating the epidemiology of future C. rugosa infections.

PMID- 8735105
TI  - Longitudinal study of molecular epidemiology of small round-structured viruses in
      a pediatric population.
AB  - Small round-structured viruses (SRSV), recently designated members of the family
      Caliciviridae, can now be readily subtyped by amplification of a defined portion
      of their genome by reverse transcription-PCR and then by identification of the
      amplicons with specific probes by Southern blotting. A longitudinal survey (from
      1991 to 1995) was conducted to determine the genotypes of the SRSV present in
      pediatric stool specimens from patients with sporadic cases of gastroenteritis.
      It was found that almost all viruses were of the G-2 genotype, and on probing,
      the subtype P2-B was predominant but the frequencies of the different subtypes
      varied from year to year. A survey of the genotypes of SRSV from community
      outbreaks from 1995 showed that the G-2 genotype was also predominant and that
      the distribution of its subtypes was similar to that seen in sporadic cases of
      diarrhea in pediatric patients over the same time period. It was concluded that
      there is a succession of subtypes of SRSV in our pediatric population over time.
      This distribution of genotypes in sporadic cases of pediatric gastroenteritis may
      reflect the distribution in community outbreaks occurring at the same time.

PMID- 8735106
TI  - Typing of Staphylococcus aureus by PCR for DNA sequences flanked by transposon
      Tn916 target region and ribosomal binding site.
AB  - The continuous intra- and interhospital spread of multiresistant Staphylococcus
      aureus demands a rapid molecular typing system. This study describes the
      fingerprinting of S. aureus by PCR amplification of DNA sequences flanked by the
      target site for transposon Tn916 and the ribosomal binding site and neighboring
      nucleotides (target 916-Shine-Dalgarno PCR [tar 916-shida PCR]). Both starting
      points for PCR are known to be randomly distributed on the S. aureus chromosome.
      By use of SmaI-macrorestriction patterns as the reference method it was shown
      that this PCR genotyping discriminates among strains of the major clonal groups
      of the species S. aureus (strains with phage patterns 29, +, 94, 96, and 95 as
      well as group II and group III patterns) and identifies the six epidemic
      methicillin-resistant S. aureus strains prevalent in German hospitals. All of the
      investigated strains including methicillin-sensitive. S. aureus were typeable.
      Tar 916-shida patterns are stable during the dissemination of epidemic
      methicillin-resistant S. aureus among different hospitals.

PMID- 8735107
TI  - Diagnostic implications of kinetics of immunoglobulin M and A antibody responses
      to Toxoplasma gondii.
AB  - We evaluated immunoglobulin M (IgM) and IgA assays that could improve the
      predictive value for recently acquired toxoplasma infection for patients with
      positive screening test results. Follow-up sera were collected from 82 patients
      whose initial serum specimen had a reactive anti-Toxoplasma gondii IgM result.
      According to the evolution of the immune response, patients were divided
      retrospectively into two groups: one in which a recent infection was unlikely and
      the other one with an evolving immune response suggestive of recent toxoplasma
      infection. All IgM and one of three IgA assays used in the study are suitable for
      screening pregnant patients, with a negative predictive value of 100%. The
      predictive value of positive results is much lower because of the low prevalence
      of acute toxoplasmosis in pregnant women and the long persistence of IgM after
      acute infection. In the present study, all except one IgM enzyme immunoassay
      remained positive well beyond 6 months after the initial sample was tested. The
      IgM immunofluorescence test had the shortest persistence of positivity in most
      cases. IgA tests were either too insensitive or remained reactive too long to be
      useful for screening pregnant patients. Interpreting enzyme immunoassays with
      modified cutoff values and the combination of two tests could improve the
      predictive value of positive results to about 80% in terms of recent infection.

PMID- 8735108
TI  - Serological diagnosis of ovine enzootic abortion by comparative inclusion
      immunofluorescence assay, recombinant lipopolysaccharide enzyme-linked
      immunosorbent assay, and complement fixation test.
AB  - Since the 1950s, serological diagnosis of ovine enzootic abortion (OEA), caused
      by strains of Chlamydia psittaci, has been based mainly on the complement
      fixation test (CFT), which is neither particularly sensitive nor specific since
      antibodies to other chlamydial and enterobacterial pathogens may be detected. In
      this study. a recombinant enzyme-linked immunosorbent assay (rELISA) (medac,
      Hamburg, Germany), based on a unique chlamydial genus-specific epitope of
      Chlamydia trachomatis L2 lipopolysaccharide, was evaluated for sensitivity and
      specificity as a primary screening assay for OEA by comparison with the CFT. A
      comparative inclusion immunofluorescence assay (IFA), in which antibody titers to
      C. psittaci and Chlamydia pecorum were examined, was used as the reference test
      for 573 serum samples from four flocks. Reactivity to C. pecorum was measured
      since inapparent intestinal infections by C. pecorum are believed to be common in
      British flocks. In detecting positive sera from an abortion-affected flock, in
      which a C. pecorum infection was also suggested by IFA, the rELISA outperformed
      the CFT with significant evidence for increased sensitivity (P = 0.003). In two
      flocks in which C. pecorum infections alone were suggested by IFA, the rELISA and
      CFT were prone to detect low levels of false-positive results, but the values
      were not significant. The rELISA provided results in one flock in which sera that
      were anticomplementary could not be resolved by the CFT. In another flock in
      which abortion had not occurred but infection by both chlamydial species was
      suspected, no significant difference was found between the sensitivities of the
      rELISA and CFT. The rELISA could not differentiate ovine C. psittaci and C.
      pecorum infections but was shown to be a more sensitive primary screening test
      for OEA than was the CFT, particularly where abortion had occurred and even when
      antibodies due to additional inapparent infection(s) by C. pecorum were present.

PMID- 8735110
TI  - Genetic variation in Australian spotted fever group rickettsiae.
AB  - Rickettsiae were isolated by cell culture of buffy coat blood from six patients
      with spotted fever from southeastern Australia and Flinders Island in Bass
      Strait. The isolates were genetically compared with two previous Rickettsia
      australis patient isolates. The genus-specific 17-kDA genes from the isolates
      were compared after DNA amplification and restriction fragment analysis of the
      amplified DNA. This comparison revealed that mainland rickettsial isolates from
      southeastern Australia were identical to two previous isolates of R. australis
      from northeastern Australia. Rickettsial isolates from Flinders Island were
      distinct from the mainland isolates. The 16S rRNA gene sequences from the
      isolates were determined and compared. The Flinders Island rickettsial agent was
      most closely related (0.3% structural divergence) to Rickettsia rickettsii,
      Rickettsia conorii, and Rickettsia slovaca. The Flinders Island rickettsial agent
      was 1.3 and 2.1% structurally divergent from R. australis and Rickettsia akari,
      respectively. The 16S rRNA gene sequence from the Flinders Island agent shows
      that this rickettsia is more closely related to the rickettsial spotted fever
      group than is R. australis. We conclude that there are two populations of spotted
      fever group rickettsiae in Australia and propose that the genetically distinct
      causative organism of Flinders Island spotted fever be designated Rickettsia
      honei. The extent of distribution and animal host reservoirs remain to be
      elucidated.

PMID- 8735109
TI  - Comparison of outbreak and nonoutbreak Acinetobacter baumannii strains by
      genotypic and phenotypic methods.
AB  - Thirty-one Acinetobacter baumannii strains, comprising 14 strains from 14
      outbreaks in different northwestern European cities and 17 sporadic strains, were
      compared by investigating various properties of the strains including biotype,
      antibiogram, cell envelope protein electrophoretic profile, ribotype pattern, and
      the band pattern generated by a novel genomic fingerprinting method, named AFLP,
      which is based on the selective amplification of restriction fragments. Results
      showed that 12 strains from unrelated outbreaks were linked together in two
      clusters according to their similarities by these typing methods, whereas
      sporadic strains were more heterogeneous. Outbreak strains appeared to be
      markedly more resistant to antibiotics than nonoutbreak strains. The uniformity
      of typing characters in two sets of outbreak strains suggests that strains in
      each cluster have a common clonal origin.

PMID- 8735111
TI  - Karyotype instability in Cryptococcus neoformans infection.
AB  - The electrophoretic karyotypes of 32 clinical and 3 environmental Cryptococcus
      neoformans isolates from New York City were studied by contour clamped
      homogeneous electrophoresis. There was extensive variation among the
      electrophoretic karyotypes of isolates from different patients. Sequential C.
      neoformans isolates from patients with chronic or relapsing infection had very
      similar karyotypes. However, minor differences in electrophoretic karyotypes were
      detected among sequential isolates from 50% of the patients studied, suggesting
      the occurrence of chromosomal rearrangements or deletions in vivo. This
      hypothesis was tested by infecting mice, recovering isolates from mouse organs,
      and comparing the electrophoretic karyotypes before and after passage. Three
      clinical and three environmental strains were studied before and after passage in
      mice. Karyotype differences were detected after mouse passage for one clinical
      and two environmental strains. Our results indicate (i) extensive karyotype
      variation among isolates from a small geographic regions, (ii) a high frequency
      of electrophoretic karyotype differences among sequential isolates from
      individual patients, and (iii) the occurrence of electrophoretic karyotype
      changes during experimental infection of mice. The implications of these
      observations are discussed.

PMID- 8735112
TI  - Subspecies typing of Vibrio parahaemolyticus by pulsed-field gel electrophoresis.
AB  - Vibrio parahaemolyticus is one of the most important food-borne pathogens in
      Taiwan, Japan, and other costal regions. We report on the development of a pulsed
      field gel electrophoresis (PFGE) method for the molecular typing of this
      pathogen. Genomic DNA was digested with SfiI, and the fragments were resolved on
      1% agarose with a contour-clamped homogeneous electric field apparatus set at 190
      V and a pulse time of 3 to 80 s. A total of 130 selected isolates obtained from
      outbreaks during 1993 and 1994 on Taiwan were also characterized by this PFGE
      method. These isolates were grouped into 14 PFGE types which consisted on one to
      six patterns, and a total of 39 patterns were identified. Most of these domestic
      clinical isolates could be clustered into several major types (types A, B, C, and
      G). These major types showed relatively low degrees of similarity to several
      foreign strains and other domestic but environmental strains. Strain CCRC12863,
      which originated from Japan, was close to the group consisting of F, G, and H
      PFGE types, suggesting a clonal relationship between this Japanese strain and
      other domestic isolates.

PMID- 8735113
TI  - Case of fatal systemic infection with an Aureobacterium sp.: identification of
      isolate by 16S rRNA gene analysis.
AB  - The case of a 75-year-old man who succumbed to a disseminated infection most
      likely caused by a species of the genus Aureobacterium is reported.
      Identification of the isolate was achieved by comparative 16S rRNA gene analysis.
      Aureobacteria are commonly found in the environment. However, only recently have
      they been recognized as a cause of infections including septicemia and soft
      tissue infections. To our knowledge, this is the first documentation of a fatal
      infection caused by an Aureobacterium sp.

PMID- 8735114
TI  - Genetic dissimilarity of two fluconazole-resistant Candida albicans strains
      causing meningitis and oral candidiasis in the same AIDS patient.
AB  - We describe a patient with AIDS who simultaneously developed Candida meningitis
      with three positive cerebrospinal fluid cultures and oral candidiasis. This
      patient also had a history or recurrent episodes of oral candidiasis treated with
      fluconazole. The patient did not respond to this therapy but was cured with
      amphotericin B and flucytosine. In vitro susceptibility tests revealed that each
      infection was caused by fluconazole-resistant Candida albicans isolates. Strain
      delineation by karyotyping, NotI restriction pattern analysis, hybridization with
      the specific probe 27A, and PCR fingerprinting with the phage M13 core sequence
      clearly demonstrated that meningitis and oral thrush were caused by two
      genetically different isolates.

PMID- 8735115
TI  - Discrepancies between results by E-test and standard microbroth dilution testing
      of Streptococcus pneumoniae for susceptibility to vancomycin.
AB  - Vancomycin susceptibility testing of Streptococcus pneumoniae by the E-test
      consistently resulted in MICs that were at the upper limit of the 1-microgram/ml
      susceptible category defined by current National Committee for Clinical
      Laboratory Standards guidelines and were always higher than MICs obtained by
      microbroth dilution. Three of five E-test results for S. pneumoniae ATCC 49619
      were higher than the acceptable limits.

PMID- 8735116
TI  - The porA alleles are identical in subgroup III serogroup A Neisseria meningitidis
      strains isolated in China in the 1960s and 1980s.
AB  - The porA genes from serogroup A, subgroup III strains isolated in the People's
      Republic of China in 1966 and in 1984 and 1985 were amplified by PCR at an
      annealing temperature of 75 degrees C. The DNA sequences (5 strains) and the
      restriction patterns generated by MspI (14 strains) were identical, unlike the
      results reported by Peixuan et al. (Z. Peixuan, H. Xujing, and X. Li, J. Clin.
      Microbiol. 33:458-462, 1995). Furthermore, PCR products which were amplified at
      an annealing temperature of 60 degrees C, as described by Peixuan et al., were
      heterogeneous in our study.

PMID- 8735117
TI  - Prevalence of fluorescent monoclonal antibody-nonreactive Neisseria gonorrhoeae
      in five North American sexually transmitted disease clinics.
AB  - We compared a direct fluorescent monoclonal antibody (DFA) test with alternative
      enzymatic and fermentation tests for identifying presumptive gonococcal isolates
      in a systematic sample from patients attending five sexually transmitted disease
      clinics in five cities. Fourteen (2.5%) of 556 isolates from three clinics were
      nonreactive with DFA confirmatory reagent and reactive by both the Quad-Ferm
      (BioMerieux Vitek Inc.) and the Rapid NH (Innovative Diagnostic Systems, Inc.)
      tests. The prevalence of DFA-nonreactive Neisseria gonorrhoeae isolates varies
      geographically and is independent of local methods for the identification of
      possible gonococci.

PMID- 8735118
TI  - Genetic characterization of rabies field isolates from Venezuela.
AB  - Twenty samples from cases of rabies in humans and domestic animals diagnosed in
      Venezuela between 1990 and 1994 and one sample from a vampire bat collected in
      1976 were characterized by reactivity to monoclonal antibodies against the viral
      nucleoprotein and by patterns of nucleotide substitution in the nucleoprotein
      gene. Three antigenic variants were found: 1, 3, and 5. Antigenic variant 1
      included all samples from dogs and humans infected by contact with rabid dogs.
      Unique substitutions permitted identification of two separate outbreaks of dog
      rabies in the Maracaibo Depression and Los Llanos region and in the Andean region
      of Venezuela. Samples from the vampire bat and two head of cattle were
      characterized as antigenic variant 3 and showed a nucleotide sequence homology of
      96 to 98% to each other and to samples of vampire bat-associated rabies
      throughout Latin America. Ten of the remaining 12 samples were characterized as
      antigenic variant 5. Genetic studies indicated that 11 of these samples formed a
      highly homologous and distinctive group but were closely related to samples of
      vampire bat-associated rabies. The 12th sample of variant 5 (from a cat) showed
      only 78 to 80% genetic homology to samples of rabies associated with vampire
      bats. The application of antigenic and genetic typing to rabies surveillance in
      Latin America is essential to improve control programs. Recognition of the source
      of outbreaks of dog rabies and identification of wildlife species maintaining
      sylvatic cycles of rabies transmission permit better utilization of public health
      resources.

PMID- 8735119
TI  - Complicated soft tissue infection with prepatellar bursitis caused by
      Paecilomyces lilacinus in an immunocompetent host: case report and review.
AB  - Documented Paecilomyces lilacinus infections are quite rare. Most reports involve
      immunocompromised patients or implanted objects. We report the first case of
      complicated soft tissue infection caused by P. lilacinus in an immunocompetent
      host. The spectrum of infections involving this fungus is reviewed.

PMID- 8735120
TI  - Extended incubation of culture plates improves recovery of Bordetella spp.
AB  - Extended incubation of culture plates was studied to see if the recovery of
      Bordetella spp. from nasopharyngeal swabs could be improved. Forty-eight
      Bordetella isolates were recovered from 103 children (overall positive-culture
      rate, 46.6%) who met the clinical case definition of pertussis. Seven of 44 (16%)
      B. pertussis isolates and 2 of 4 (50%) B. parapertussis isolates were recovered
      only after extended incubation of nasopharyngeal cultures up to 12 days.

PMID- 8735121
TI  - Testing of susceptibility of Mycobacterium tuberculosis to isoniazid and rifampin
      by mycobacterium growth indicator tube method.
AB  - We tested isolates of Mycobacterium tuberculosis recovered from 117 patients for
      their susceptibilities to isoniazid (INH) and rifampin (RIF) by the Centers for
      Disease Control and Prevention's disk modification of the indirect method of
      proportions (MOP) test and a three-tube mycobacteria growth indicator tube (MGIT;
      BBL) antimycobacterial susceptibility test (AST). Sixty-seven of the M.
      tuberculosis isolates were recovered from Lowenstein-Jensen (BBL) subcultures,
      and 50 of the isolates were recovered from MGIT cultures of samples from various
      body sites. For the MGIT AST method, 0.5 ml of test organism suspension was
      inoculated into an MGIT with 0.1 micrograms of INH per ml, an MGIT with 1.0
      micrograms of RIF per ml, and growth control MGIT. The tubes were incubated at 37
      degrees C and were examined daily. The MGIT AST results were interpreted as
      follows: susceptible if the tubes containing INH or RIF did not fluoresce within
      2 days of the time that the positive growth control fluoresced and resistant if
      the tubes containing INH or RIF did fluoresce within 2 days of the time that the
      positive growth control fluoresced. The mean time fluorescence for the positive
      growth control was 5.5 days. The two methods were in agreement for 114 of the 117
      isolates from patients, while for 3 isolates there were minor discordant results.

PMID- 8735122
TI  - Detection of hepatitis E virus RNA in stools and serum by reverse transcription
      PCR.
AB  - Stools and sera collected during an experimental hepatitis E virus (HEV)
      infection in monkeys and collected from humans with acute HEV infections during
      epidemic and sporadic cases were analyzed by reverse transcription-PCR. Two
      methods for RNA purification were compared. Proteinase K digestion and
      phenolchloroform extraction were more efficient than guanidinium isothiocyanate
      extraction in improving the sensitivity and specificity for the detection of HEV
      genomes.

PMID- 8735123
TI  - Comparison of cell culture, mouse inoculation, and PCR for detection of
      Toxoplasma gondii: effects of storage conditions on sensitivity.
AB  - The sensitivity of detection of a wild-type strain of Toxoplasma gondii by cell
      culture, mouse inoculation, and PCR was determined following sample storage under
      conditions to which clinical specimens may be subjected during transport to the
      testing laboratory. Sample storage at -20 degrees C significantly decreased the
      sensitivity of mouse inoculation. The sensitivity of cell culture decreased with
      sample storage at 4 and -20 degrees C. The sensitivity of PCR was reduced by
      storage at 4 degrees C for 48 h, freezing, and heating. These findings have
      implications for the selection of appropriate methods for the direct detection of
      T. gondii organisms in suboptimally transported clinical samples.

PMID- 8735124
TI  - Highly toxic clone of Actinobacillus actinomycetemcomitans in geographically
      widespread cases of juvenile periodontitis in adolescents of African origin.
AB  - The bacterium Actinobacillus actinomycetemcomitans has been implicated in the
      pathogenesis of juvenile periodontitis as the etiologic agent on the basis of
      several lines of circumstantial evidence. A matter of extensive debate is whether
      A. actinomycetemcomitans is an exogenous contagious pathogen or an opportunistic
      pathogen that resides in the normal oral microflora. Here we show evidence of a
      single clone of A. actinomycetemcomitans isolated from multiple patients with
      juvenile periodontitis in members of families of African origin living in
      geographically widespread areas. The clone is characterized by a 530-bp deletion
      in the leukotoxin gene operon, resulting in a significantly increased production
      of leukotoxin.

PMID- 8735125
TI  - Comparison of Binax Legionella Urinary Antigen EIA kit with Binax RIA Urinary
      Antigen kit for detection of Legionella pneumophila serogroup 1 antigen.
AB  - The Legionella Urinary Antigen EIA kit (Binax, Portland, Maine) was compared with
      the EQUATE RIA Legionella Urinary Antigen kit (Binax) for its ability to detect
      the presence of urinary antigens to Legionella pneumophila serogroup 1. Urine
      specimens from patients without Legionnaires' disease (n = 33) were negative by
      both methods (specificity, 100%). Twenty (77%) of 26 urine specimens from
      patients with Legionnaires' disease positive by the radioimmunoassay kit were
      also positive by the enzyme immunoassay (EIA) kit. If the cutoff for a positive
      EIA result were lowered to a ration of > or = 2.5, 23 of 26 (88%) urine specimens
      would have been positive by EIA and the specificity would remain 100%. Use of the
      EIA kit is an acceptable method for detecting L. pneumophila serogroup 1 urinary
      antigens by laboratories that do not want to handle radioactive materials.

PMID- 8735126
TI  - Enhanced amplification of hepatitis C virus (HCV) cDNA by PCR: detection of HCV
      RNA in archival sera.
AB  - A reverse transcription-PCR assay which successfully amplified hepatitis C virus
      RNA from poorly stored archival sera was optimized. Maximum sensitivity was
      achieved with Moloney murine leukemia virus RNase H- reverse transcriptase and by
      a single round of PCR amplification of a short (112-bp) fragment of the 5'
      untranslated region of the viral genome.

PMID- 8735127
TI  - Duration of incubation of fungal cultures.
AB  - To determine the optimum duration of incubation for recovery of fungi, the
      results of 2,173 consecutive clinical cultures were reviewed. Overall, 94% of
      fungal isolates were detected by day 7 and 98% were detected by day 14. Yeasts
      were usually (98%) detected within the first week of incubation. Recovery of
      molds required more time, but 81% were detected by day 7 and more than 96% were
      detected by day 14.

PMID- 8735129
TI  - Rare association of human herpesvirus 6 DNA with human papillomavirus DNA in
      cervical smears of women with normal and abnormal cytologies.
AB  - We investigated by nested PCR the possible association of human herpesvirus 6
      (HHV-6) and human papillomavirus (HPV) genomes in the cervixes of 109 women with
      normal and abnormal cytological smears. HPV DNA was detected in 8.33% of 24 women
      with normal cytologies and in 41.1% of 85 women with abnormal cytologies; the
      proportion of HPV DNA was directly related to the severity of the lesions. HHV-6
      DNA was found in only one patient, who had a cytological pattern of koilocytosis.
      The HHV-6 genome was classified by restriction enzyme analysis as variant B. The
      study indicates that detection of the HHV-6 genome in the cervixes of women with
      a wide spectrum of gynecological complaints is a rare event and rules out the
      possible association between HHV-6 and HPV genomes in cervical cancer lesions.

PMID- 8735128
TI  - Detection of Pneumocystis carinii DNA in blood by PCR is not of value for
      diagnosis of P. carinii pneumonia.
AB  - A nested PCR which amplified a portion of the mitochondrial large-subunit rRNA
      gene of Pneumocystis carinii was used to detect P. carinii DNA in blood from
      patients with P. carinii pneumonia. P. carinii DNA was not detected in serum and
      was detected at low levels of blood cells.

PMID- 8735130
TI  - Classification of rotavirus into G and P types with specimens from children with
      acute diarrhea in New Delhi, India.
AB  - Sixty rotavirus-positive stool specimens from children with diarrhea were
      classified into G and P genotypes. G typing was done by PCR and then by
      hybridization with G type-specific (G1 to G4) oligonucleotide probes, whereas
      nested PCR was performed for P typing. Thirty-nine samples could be classified
      into both G and P types, of which P8G1 and P4G2 (33% each) genotypes were
      predominant. The P6 genotype was detected in four children with diarrhea.

PMID- 8735131
TI  - Molecular typing of nosocomial strains of Legionella pneumophila by arbitrarily
      primed PCR.
AB  - Arbitrarily primed PCR with two different primers was compared with ribotyping
      and monoclonal antibody analysis for typing Legionella strains. Applied to 11
      epidemiologically unrelated strains, arbitrarily primed PCR resulted in an index
      of discrimination of 100% with both primers. It was found able to identify an
      epidemic clone of Legionella pneumophila serogroup 1 that was isolated from both
      patients and a hot water circuit of the same hospital.

PMID- 8735132
TI  - Specific detection of methicillin-resistant Staphylococcus species by multiplex
      PCR.

PMID- 8735133
TI  - Performance of a rapid, on-site human immunodeficiency virus antibody assay in
      public health settings.

PMID- 8735134
TI  - Tissue factor expression is differentially modulated by cyclic mechanical strain
      in various human endothelial cells.
AB  - Many of the hemostatic properties of endothelium are modulated by chemical and
      mechanical stimuli. The nature of such endothelial cell (EC) responses often
      depends upon the anatomical origin of the cells within the vascular tree. In the
      present study, we used a chromogenic assay to investigate the effect of cyclic
      strain or tumor necrosis factor alpha (TNF alpha), or both, on tissue factor (TF)
      activity in human EC derived from umbilical veins (HUVEC), aortae (HAEC), and
      dermal microvessels (HMVEC). Basal TF activities were low in all three cell
      types. Incubation for 5 h with (10 ng/ml) TNF alpha resulted in quantitatively
      diverse elevation of TF activity in all three EC types. Exposure to cyclic strain
      for 5 h induced significant elevation of TF activity only in HMVEC and HAEC.
      Concomitant application of cyclic strain and TNF alpha resulted in synergistic
      elevation of TF expression only in HMVEC. Pharmacologic elevation of cyclic AMP
      (cAMP) levels and inhibition of protein kinase C (PKC) levels inhibited TNF alpha
      induced TF expression in all EC types. However, none of these treatments affected
      the stimulatory action of cyclic strain in HMVEC. Thus, we have shown that TNF
      alpha differentially increases TF activity in human EC of various origins, that
      cyclic strain variably modulates TF activity in human EC, and that both PKC and
      cAMP mediate TNF alpha-induced TF activity, whereas cyclic strain acts
      independently of these pathways. These results show differential modulation of
      the procoagulant potential of diverse human endothelial cells in vitro by
      hemodynamic stimuli.

PMID- 8735135
TI  - Intraventricular haemorrhage in preterm infants: evidence of suppressed
      fibrinolysis.
AB  - Intraventricular hemorrhage (IVH) in premature infants may be related to the
      immaturity of the vascular bed in the germinal matrix. We measured six hemostatic
      parameters whose alterations may represent an additional risk factor for IVH in
      preterm infants. On postnatal day 1 there were differences between plasminogen
      activator inhibitor-1 (PAI-1) activity and antigen, of both full-term and preterm
      infants with and without IVH (P < 0.05). Preterms with IVH were different to both
      full-terms and preterms without IVH. No difference was observed in plasma
      concentrations of fibrinogen, plasminogen and von Willebrand factor. Plasma
      concentrations of antithrombin III were significantly higher in full-term infants
      than in preterm infants. The difference between the platelet counts of preterm
      infants with and without IVH was not significant (P > 0.05). Elevation of
      crosslinked fibrin degradation products (XDP), determined by the SimpliRED D
      dimer test, correlated in four out of five premature infants with the diagnosis
      of IVH by ultrasonography. No elevation of D-dimer XDP was observed in premature
      infants without IVH (11/12) and full-term infants (6/6). In conclusion, a
      hypercoagulable state, indicated by a rise in D-dimer XDP, may be initiated by
      some types of trauma to fragile blood vessels of the preterm infants who develop
      IVH. This hypercoagulability is further exacerbated by the increased release of
      PAI-1 leading to suppressed fibrinolysis.

PMID- 8735136
TI  - Factor V Leiden-like behaviour of animal plasma and its use for calibration of
      activated protein C-dependent assays.
AB  - We studied the sensitivity of various animal plasmas to activated human protein C
      (APC) and found an impaired response in the order monkey < horse < pig < dog <
      rabbit. We assume that this effect was mainly caused by differences in the APC
      cleavage region of factor V, as recently described for the factor V Leiden
      mutation in humans. In APC-dependent assays, which are based on the inactivation
      of factor Va, 5% (v/v) rabbit plasma added to human plasma mimicked the APC
      response seen in heterozygous carriers of factor V Leiden; 20% rabbit plasma gave
      results similar to those seen in homozygotes. We exploited this factor V Leiden
      like behaviour to prepare plasma standards for calibration of APC-dependent
      assays by mixing rabbit and human plasmas. The 0% value was assigned to the
      clotting time in the absence of APC, while the 100% value was assigned to the
      clotting time in presence of APC. A normal human plasma pool was used as
      reference. These standards were used to establish reference curves. On automated
      coagulation analyzers, the results obtained were automatically reported as
      'percent normal'. This not only simplified evaluation, but also improved the
      comparability of results.

PMID- 8735137
TI  - Manifestation of cryptic fibroblast tissue factor occurs at detergent
      concentrations which dissolve the plasma membrane.
AB  - Cultured fibroblasts treated with increasing concentrations of detergents
      expressed only encrypted levels of tissue factor activity (measured by fX
      activation in the presence of fVIIa), characteristic of undamaged cells, until
      each detergent reached a critical concentration at which the cryptic tissue
      factor activity was manifested. Beyond the narrow ranges of concentrations over
      which the detergents stimulated tissue factor activity, the detergents were
      inhibitory. Studies with Triton X-100 and octyl glucoside revealed that
      manifestation of tissue factor activity coincided with breakdown of the plasma
      membrane. The magnitude of the increased tissue factor activity differed among
      detergents, with octyl glucoside giving the largest response. The tissue factor
      that was active after Triton X-100 treatment remained mostly associated with the
      insoluble cell residue, whereas the concentration of octyl glucoside which
      stimulated activity released tissue factor activity into the supernatant.
      Radiolabeled antibody against human tissue factor was used to show that a small
      percentage of the total accessible tissue factor remained in the insoluble
      fraction after treatment with either non-ionic detergent. Chromatographic
      analysis of lipids extracted from cells treated with detergents and dansyl
      chloride showed dansyl-reactivity of phosphatidylserine on intact cells, and
      solubilization of membrane lipids at sublytic concentrations of detergents. These
      findings reveal that there is a critical level of detergent-induced membrane
      damage at which tissue factor activity is maximally expressed, in essentially an
      all-or-none manner. The results are consistent with a major role for phospholipid
      asymmetry in regulation of tissue factor specific activity, but require either
      maintenance of asymmetry during sublytic detergent perturbation of the plasma
      membrane or additional control mechanisms.

PMID- 8735138
TI  - Fibroblasts restrict tissue factor from vesicles which form in response to low
      concentrations of detergent.
AB  - Studies of tissue factor activity on fibroblasts have found that manifestation of
      the otherwise cryptic activity is evoked by Triton X-100 or octyl glucoside at
      concentrations that lyse the cells. Even though sublytic concentrations of the
      detergents extract membrane lipids into the soluble phase, they were without
      effect on tissue factor activity. Those experiments led us to conclude that
      either the fibroblasts maintain plasma membrane lipid asymmetry even as lipids
      are extracted by the detergents, up to the onset of lysis, or additional
      mechanisms for regulation of tissue factor specific activity were operative.
      Using phase contrast and immunofluorescent microscopy, we now show that at least
      one additional regulatory mechanism is indeed operative. In response to sublytic
      concentrations of octyl glucoside or Triton X-100, the cells release vesicles
      from which tissue factor antigen is excluded. Lytic concentrations of the
      detergents preclude this segregation, leaving only low amounts of tissue factor
      antigen associated with the adherent cytoskeletons. Two-color staining reveals
      marked tissue factor-actin filament co-localization, which implies the potential
      for cytoskeletal participation in the observed tissue factor segregation. We
      propose that tissue factor activity is indeed regulated by the phospholipids with
      which it is associated and the degree to which phosphatidylserine is available on
      the membrane surface, but the cells possess additional mechanisms by which the
      association of tissue factor with potentially procoagulant membrane domains is
      controlled.

PMID- 8735139
TI  - Lupus anticoagulant and thromboembolism: evaluation of fibrinogen, natural
      inhibitors and molecular markers of thrombosis.
AB  - It has been speculated that an impairment in anticoagulant pathways (protein C
      (PC), protein S (PS), resistance to activated protein C (APC)), may contribute to
      the thrombotic tendency in lupus anticoagulant (LA) patients. Increased plasma
      levels of fibrinogen are predictive for arterial thrombosis and increased
      molecular markers of thrombosis are indicative for activation of the clotting
      cascade. We investigated 25 patients (20 women) with LA. All patients were
      stratified according to their thromboembolic history and women according to their
      history of fetal loss. Eighteen patients had a history of venous or arterial
      thrombosis, or both. Seven of 16 women with at least one pregnancy had a history
      of fetal loss. The interrelation among the levels of fibrinogen, PC and PS, and
      resistance to APC, thrombin-antithrombin III complexes (TAT), prothrombin
      fragment F1 + 2, D-dimer and the history of thrombotic events and obstetric
      complications in patients with LA were evaluated. LA patients with a history of
      venous or arterial thrombosis had a significantly higher fibrinogen level than LA
      patients without (mean 366 versus 304 mg/dl; P = 0.018). Among 16 women a
      slightly lower mean TAT level in women with fetal loss was found (2.4 versus 4.3
      ng/ml; P = 0.02). No other statistically significant difference in the remaining
      parameters was yielded in both analyzed subgroups. The results of the study
      suggest an association between increased fibrinogen levels and the history of
      venous or arterial thrombosis, or both, in patients with LA. In the other
      investigated parameters, no relationship to the thrombotic or obstetric history
      was found.

PMID- 8735140
TI  - Binding of calcium ions and their effect on clotting of fibrinogen Milano III, a
      variant with truncated A alpha-chains.
AB  - Calcium ions are known to be required for normal polymerisation of fibrin
      monomers. Normal human fibrinogen has three high-affinity calcium binding sites.
      Two of these are located in the D-domains whereas the third binding site was
      tentatively assigned either to the E-domain or to the C-terminal part of the A
      alpha-chain. Furthermore, binding of calcium to the low-affinity binding sites (n
      > or = 10) facilitates fibrin monomer polymerisation. In several abnormally
      clotting fibrinogen variants, the polymerisation defect was partially normalised
      following addition of calcium ions. In this study, we show normal binding of
      calcium to fibrinogen Milano III, a homozygous fibrinogen variant with truncated
      A alpha-chains (A alpha 452 Gly-Pro-Asp-->Trp-Ser-Stop). These results confirm
      that the C-terminal parts of the A alpha-chains beyond residue 451 Ile are not
      involved in calcium binding. The thrombin time was severely prolonged and the
      final clot turbidity was strongly reduced in fibrinogen Milano III. Moreover,
      calcium ions did not significantly improve the abnormal clotting behavior of this
      dysfibrinogen. The polymerisation defect in fibrinogen Milano III appears to be
      due to truncated A alpha-chains as well as to the disulphide-linked albumin.

PMID- 8735141
TI  - Activation of human prothrombin by porcine aortic endothelial cells--a potential
      barrier to pig to human xenotransplantation.
AB  - A potential solution to the shortage of human organs for transplantation lies in
      the use of animal organs with the pig as the most likely donor. Perfusion of
      porcine organs with human blood, however, results in hyperacute rejection
      (xenograft reaction) which occurs within minutes to hours and is characterised by
      intravascular thrombosis. The pathogenesis of this xenograft reaction is
      attributed to xenoreactive natural antibodies (XNA) binding to epitopes on
      porcine endothelium activating complement with subsequent haemostatic activation.
      We have investigated whether there is direct activation of human coagulation by
      porcine endothelium in the absence of XNA and complement. Previous experiments
      demonstrated possible pathological activation of the common pathway, thus human
      prothrombin and factor X were added separately to porcine endothelium and
      monitored for activation. Human prothrombin was activated by porcine but not
      human endothelium. There was no activation of factor X. Hirudin inhibited
      prothrombin activation suggesting that a conformational change may occur in
      prothrombin on binding to porcine endothelium, such that its catalytic centre is
      exposed with subsequent autocatalytic cleavages. If this in vitro observation of
      direct prothrombin activation is translated to the in vivo situation then this
      phenomenon may pose a non-immunological obstacle to pig to human
      xenotransplantation.

PMID- 8735142
TI  - Activated protein C resistance phenotype and genotype in patients with primary
      antiphospholipid syndrome.
AB  - We studied both inherited and acquired activated protein C (APC) resistance in a
      group of 22 patients with primary antiphospholipid syndrome (APS). The APC
      resistance genotype was assessed using a PCR-based analysis for the factor V
      R506Q (Leiden) mutation. One patient with primary APS was found to be
      heterozygous for the factor V Leiden mutation. He and other family members were
      affected by severe thrombophilia and had a familial form of primary APS. The APC
      resistance phenotype was assessed by measuring the prolongation of the activated
      partial thromboplastin clotting time in response to APC. It was found in five out
      of six patients with APS, in one of them transiently. We have found that the APC
      resistance phenotype is more frequent than the genotype in primary APS. It would
      seem that patients with thrombophilia should be investigated for APC resistance
      even if found to have antiphospholipid antibodies and/or lupus anticoagulants.

PMID- 8735143
TI  - Resistance to activated protein C mimicking dysfunctional protein C: diagnostic
      approach.
AB  - It has been reported that resistance to activated protein C interferes with
      functional plasma-based coagulation assays of protein C, mimicking a type II
      deficiency. In this study we confirm and extend these findings. In our laboratory
      approximately 25% of patients with resistance to activated protein C have an
      apparent type II protein C deficiency. It is important for rapid and accurate
      diagnosis to be able to confirm or exclude a dysfunction of protein C associated
      with resistance. We therefore propose a new coagulation assay that requires first
      absorption of protein C from plasma, activation with a snake venom and
      measurement of its anticoagulant activity. This assay is quick, reproducible and
      can be automated. It is also insensitive to the presence of resistance to
      activated protein C and allows detection of all types of protein C deficiency.
      This is important when screening for inherited causes of thrombophilia since more
      than one defect might be present and interference from resistance to activated
      protein C is common.

PMID- 8735144
TI  - Platelet adhesion to late fibrinogen degradation products.
AB  - Evidence is emerging for the regulation of platelet function at sites of vascular
      injury or thrombosis by multiple platelet recognition sites in fibrinogen. This
      study examined the interaction of platelets with immobilized fibrinogen
      degradation products, fragments D and E. A 60 kDa D fragment (D60) and 30 kDa
      fragment E supported the adhesion of activated platelets in a static system,
      despite the absence of gamma chain 400-411 dodecapeptide and RGD sequences.
      Moreover, platelet adhesion to these fragments was incompletely inhibited by
      EDTA. In the absence of divalent cations, ADP-stimulated platelet adhesion to
      fragments D60 or E constituted 31 +/- 12% and 33 +/- 10% (mean +/- SD,n = 23) of
      adhesion to intact fibrinogen in the presence of divalent cations, respectively.
      This EDTA-resistant adhesion was distinctly modulated by thrombin which
      preferentially supported platelet adhesion to fragment E, and chymotrypsin which
      selectively supported platelet adhesion to fragment D60. Furthermore, two potent
      inhibitors of fibrinogen binding, the 10E5 monoclonal antibody directed against
      the GPIIb-IIIa complex and the RGDF peptide, inhibited EDTA-resistant platelet
      adhesion to fragment D60 but not to fragment E. These data suggest the presence
      of novel, non-RGD, non-dodecapeptide containing platelet recognition sequences in
      both fibrinogen D and E domains which support divalent cation dependent and
      independent platelet adhesion via potentially unique binding mechanisms.

PMID- 8735145
TI  - Recurrent thrombosis due to compound heterozygosity for factor V Leiden and
      factor V deficiency.
AB  - A point mutation in the factor V gene (factor V Leiden) is the most common cause
      of familial thrombophilia. Patients with factor V Leiden have an increased risk
      of thrombosis, particularly those homozygous for the mutation. However, the
      phenotype in individuals with the mutation is variable, suggesting that other
      factors influence thrombotic risk. We describe for the first time a family in
      which two independent defects in factor V co-exist: heterozygosity for factor V
      Leiden and factor V deficiency. Compound heterozygosity for these two defects
      results in a phenotype similar to a homozygous factor V Leiden state with
      profound resistance to APC and recurrent thrombosis.

PMID- 8735146
TI  - Is heparin the ideal anticoagulant in patients with a high plasma leukocyte
      elastase level?

PMID- 8735147
TI  - Immunoreactivity of cross-linked fibrin derivatives (D-dimer) and monoclonal
      antibodies.

PMID- 8735148
TI  - Social and psychological resources in the oldest old.
AB  - The purpose of this study was to compare mental health resources, activities of
      daily living, and social and economic resources in three age groups:
      centenarians, octogenarians, and sexagenarians. Two hundred and seventy-two older
      adults were assessed with the Older Americans Resources and Services Survey
      (OARS). Frequency analyses revealed that centanarians rated lower in social and
      psychological resources than the other two age groups.

PMID- 8735149
TI  - Mental health and number of illnesses are predictors of nutritional risk in
      elderly persons.
AB  - Data from a sample of elders (N = 240) in their 60s, 80s, and 100s indicated that
      nutritional risk was positively correlated with age (p < .05), ethnicity (p <
      .05), number of illnesses (p < .001), and poor mental health (p < .001).
      Regression analysis suggested that number of illnesses (p = .0001) and mental
      health (p = .0005) were the most significant predictors of nutritional risk and
      that these two variables explained 28.8% of the variance for the total sample.
      Somatic factors of mental health were significantly related to nutritional risk
      (p = .0001). Regression analyses for these age cohorts indicated that mental
      health was a highly significant predictor of nutritional risk for 80- to 89-year
      olds (p = .004), particularly somatic aspects of mental health (p = .03).
      Although somatic factors were highly significant among centenarians (p = .005),
      overall mental health was not a predictor of nutritional risk in centenarians (p
      = .08). Number of illnesses was the primary predictor of nutritional risk among
      sexagenarians and octogenarians.

PMID- 8735150
TI  - Older adults' strategic superiority with mental multiplication: a generation
      effect assessment.
AB  - Recent studies suggest that older adults' simple arithmetic fact knowledge may be
      superior to that of college students, as evidenced by the older adults' more
      frequent use of direct memory retrieval (versus computation) as an answer
      generation mechanism. Whereas previous studies assessed strategy selection via
      self-report and/or reaction time, we have adopted the "generation effect"
      paradigm-better memory for items that are subject-generated versus those that are
      simply read. The memorial advantage of generation depends in part on the degree
      of effort involved in generating versus reading an item. Because direct retrieval
      is less effortful than computation, we expected qualitative age differences in
      answer generation strategies to manifest themselves as age differences in the
      magnitude of the generation effect, especially for problems with larger answers.
      With simple multiplication problem materials, the expected Age x Problem Size
      interaction was found. In a verbal materials comparison condition, the size of
      the generation effect did not differ across adult age.

PMID- 8735151
TI  - Aging effects on auditory processing: an event-related potential study.
AB  - Deviant tones randomly embedded in a sequence of standard tones elicit an event
      related potential (ERP) called the mismatch negativity (MMN), which reflects
      automatic stimulus-change detection in the human auditory system. When the tones
      are attended, deviant tones elicit also an N2b component that partly overlaps the
      MMN. Sequences of standard and deviant (probability 0.15) tones were presented to
      13 healthy younger and 13 older subjects. Deviant stimuli were, in separate
      blocks, either occasional shorter duration or higher frequency tones. The
      interstimulus interval (ISI) was, in separate blocks, either 0.5 s or 1.5 s, and
      in the frequency-change condition also 4.5 s. Aging affected neither frequency
      nor duration of MMN with the 0.5 s ISI. This finding indicates that automatic
      stimulus discrimination per se is not impaired with normal aging. However, with a
      4.5-s ISI the MMN/N2b-complex attenuated significantly more in the older than
      younger subjects. This suggests that the stimulus trace decays faster or that
      involuntary attention switching is less sensitive with aging.

PMID- 8735152
TI  - Upright standing and gait: are there changes in attentional requirements related
      to normal aging?
AB  - This study evaluates attentional requirements for maintaining an upright posture
      and for walking among young and elderly persons to determine if, with normal
      aging, there is a deficit and/or a modification in the allocation of the
      attentional resources necessary for balance control. Eight young adults and 8
      elderly persons were asked to respond to an auditory reaction time (RT) task
      (secondary task) while in a seated position, while in a broad-support or narrow
      support upright standing position, and while walking (primary tasks). Reducing
      the base of support yielded slower RTs for the elderly than for the young
      persons. When walking, the elderly persons adopted a slower speed than young
      persons. They also had a shorter stride length. These adaptations have been
      reported to produce a more secure gait. Even so, they responded to the probe RT
      task with greater delays than young adults. Together, the results suggest that
      normal aging requires that a greater proportion of attentional resources be
      allocated to the balance demands of postural tasks.

PMID- 8735154
TI  - Emotional priming in clinically depressed subjects.
AB  - A study is described in which the Emotional Priming Paradigm (Power and Brewin
      (1990) Cogn. Emotion 4, 39-51) was used with a group of currently depressed
      patients and a group of nondepressed controls. The results for the depressed
      patients showed significant facilitation effects on both the speed and rate of
      endorsement of negative trait adjectives when these were preceded by negative
      emotional primes. These results contrast with those obtained with the control
      subjects who failed to show such facilitation effects. The results are discussed
      in relation to the role of cognitive biases in depression.

PMID- 8735153
TI  - Age differences in the accuracy of confidence judgments.
AB  - Age differences in accuracy were investigated by having older (M = 68.6 years)
      and younger (M = 21.5 years) adults make confidence judgments about the
      correctness of their responses to two sets of general knowledge items. For one
      set, prior to making their confidence judgments, subjects made mental strategy
      judgements indicating how they had selected their answers (i.e., they guessed,
      used intuition, made an inference, or immediately recognized the response as
      correct). Results indicate that older subjects were more accurate than younger
      subjects in predicting the correctness of their responses; however, making mental
      strategy judgments did not result in increased accuracy for either age group.
      Additional analyses explored the relationship between accuracy and other
      individual difference variables. The results of this investigation are consistent
      with recent theories of postformal cognitive development that suggest older
      adults have greater insight into the limitations of their knowledge.

PMID- 8735155
TI  - The subaffective-character spectrum subtyping distinction in primary early-onset
      dysthymia: a clinical and family study.
AB  - In 1983, Akiskal proposed that primary early-onset dysthymia should be divided
      into two subtypes: subaffective dysthymia, which is a subsyndromal form of major
      mood disorder; and character spectrum disorder, which is a form of personality
      disorder with secondary dysphoria. The present study attempted to validate this
      distinction. Akiskal's (1983) criteria were applied to a sample of 97 early-onset
      dysthymic outpatients, yielding groups of 41 subaffective and 56 character
      spectrum patients. Patients were evaluated using structured interviews for Axis I
      and II disorders, family history of psychopathology, and the early home
      environment, and a comprehensive battery of questionnaires. In addition, direct
      and family history interviews were conducted with their first-degree relatives.
      There was mixed support for Akiskal's typology. Consistent with the model,
      subaffectives exhibited higher rates of major depression, depressive symptoms,
      and a number of depressive personality and cognitive features. In addition, there
      was a higher rate of alcoholism among the relatives of character spectrum
      patients. However, contrary to Akiskal's model, the groups did not differ on
      gender, unstable personality disorders, family history of mood disorders, or the
      early home environment.

PMID- 8735156
TI  - Parsing the genetic and nongenetic variance in children's depressive behavior.
AB  - Estimates of the genetic and environmental contributions to depressive behavior
      were derived using model-fitting analyses with data from a sample of 364 twin
      pairs, aged 4 to 12 years. Results suggested that genetic and nonshared
      environmental factors accounted for significant proportions of the variance in
      children's depressive symptomatology, but estimates differ for boys and girls.
      Further analyses indicated different genetic and environmental contributions for
      younger and older children. Analyses of a direct measure of shared and nonshared
      components of the environment identified specific aspects of children's
      environments which were associated with depressive behavior.

PMID- 8735158
TI  - Lower serum transcortin (CBG) in major depressed females: relationships with
      baseline and postdexamethasone cortisol values.
AB  - This study has been carried out to examine (i) transcortin or corticosteroid
      binding globulin (CBG), the major glucocorticoid transport protein, in major
      depressed versus minor depressed and normal subjects; and (ii) the relationships
      between CBG and basal and postdexamethasone cortisol or adrenocorticotropic
      hormone (ACTH) values. Serum CBG was significantly lower in major depressed than
      in minor depressed subjects and normal controls. The significant decrease in
      serum CBG was observed in major depressed women but not in major depressed men.
      In depressed subjects, there was a significant and negative relationship between
      serum CBG and severity of illness. There were significant positive relationships
      between serum CBG and basal 8:00 a.m. plasma cortisol in normal volunteers (r =
      0.87, P < 10(-4)) and depressed subjects (r = 0.40, P = 0.0002). There was no
      significant relationship between serum CBG and 24-h urinary cortisol. In
      depressed patients, there was a positive relationship between serum CBG and
      postdexamethasone cortisol (r = 0.31, P = 0.003). It is concluded that, in
      depression, serum CBG levels should be taken into consideration for the
      interpretation of baseline and postdexamethasone plasma total cortisol levels.

PMID- 8735157
TI  - Fatty acid composition in major depression: decreased omega 3 fractions in
      cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in
      cholesteryl esters and phospholipids.
AB  - Recently, there were some reports that major depression may be accompanied by
      alterations in serum total cholesterol, cholesterol ester and omega 3 essential
      fatty acid levels and by an increased C20: 4 omega 6/C20: 5 omega 3, i.e.,
      arachidonic acid/eicosapentaenoic, ratio. The present study aimed to examine
      fatty acid composition of serum cholesteryl esters and phospholipids in 36 major
      depressed, 14 minor depressed and 24 normal subjects. Individual saturated (e.g.,
      C14:0; C16:0, C18:0) and unsaturated (e.g., C18:1, C18:2, C20:4) fatty acids in
      phospholipid and cholesteryl ester fractions were assayed and the sums of the
      percentages of omega 6 and omega 3, saturated, branched chain and odd chain fatty
      acids, monoenes as well as the ratios omega 6/omega 3 and C20:4 omega 6/C20:5
      omega 3 were calculated. Major depressed subjects had significantly higher C20:4
      omega 6/C20:5 omega 3 ratio in both serum cholesteryl esters and phospholipids
      and a significantly increased omega 6/omega 3 ratio in cholesteryl ester fraction
      than healthy volunteers and minor depressed subjects. Major depressed subjects
      had significantly lower C18:3 omega 3 in cholesteryl esters than normal controls.
      Major depressed subjects showed significantly lower total omega 3 polyunsaturated
      fatty acids in cholesteryl esters and significantly lower C20:5 omega 3 in serum
      cholesteryl esters and phospholipids than minor depressed subjects and healthy
      controls. These findings suggest an abnormal intake or metabolism of essential
      fatty acids in conjunction with decreased formation of cholesteryl esters in
      major depression.

PMID- 8735159
TI  - Mood disorders: rural/urban differences in prevalence, health care utilization,
      and disability in Ontario.
AB  - This study examines whether rural Ontario differs from urban Ontario in mood
      disorder prevalence, health service use and concomitant disability. An
      epidemiologic community survey of 9953 individuals was conducted, with
      rural/urban status defined by population-density-related criteria. Overall,
      Ontario prevalence rates for depression, manic episode, and dysthymia were
      similar to previous studies, but rural rates were unexpectedly no different from
      urban ones. Nearly half of mood disorder subjects used no services, and one-third
      reported significant disability. Rural individuals with mood disorders were
      similar to their urban counterparts in service use and disability.

PMID- 8735160
TI  - Fluvoxamine and lithium in long-term treatment of unipolar subjects with high
      recurrence rate.
AB  - We prolonged from 24 to 36 months a follow-up study of unipolar subjects with a
      high probability of recurrence treated with fluvoxamine (n = 32) or lithium (n =
      32). During the extra observation period, two patients developed mania and were
      excluded from the study. There were no further recurrences in either the lithium
      or the fluvoxamine group. In our sample, previous prescriptions of tricyclics
      seem to predict a worse prognosis.

PMID- 8735162
TI  - College women's sexuality in an era of AIDS.
AB  - The author surveyed 238 heterosexual undergraduate women enrolled in a California
      university in 1993 to determine levels of perceived self-efficacy to engage in
      safer sexual behavior. She predicted that perceived self-efficacy levels would be
      related to dimensions of sexuality that may play a role in decreasing women's
      risk of sexually contracting HIV infection. These dimensions included stereotyped
      attitudes, assertiveness, communication, and safer sex behavior. For each of
      these dependent variables, she hypothesized that participants with high levels of
      perceived self-efficacy would report significantly more "favorable," or sexually
      assertive, responses than participants with low levels of perceived self
      efficacy. Analyses using t tests confirmed all main hypotheses. In addition, one
      way analyses of variance indicated that when combined with perceived self
      efficacy levels, the survey participants' relationship status significantly
      influenced their responses.

PMID- 8735161
TI  - Attitudes about condoms and condom use among college students.
AB  - The authors assessed the relationships of ethnicity, gender, previous condom use,
      and intended condom use to perceived attributes of the condom and the
      contraceptive pill in a multiethnic sample of 197 college students. Factors that
      appeared to underlie attitudes toward the condom and the Pill included prevention
      of health problems, peer acceptance, sexual pleasure and spontaneity,
      convenience, embarrassment, and effectiveness in preventing HIV and sexually
      transmitted diseases. African American participants viewed the condom more
      positively than did students from other ethnic groups and were more likely to use
      condoms than White participants were. The African Americans appeared to know less
      about the characteristics of the Pill and were less likely to use it than were
      the White respondents. Only 60% of the persons in the student sample had used
      condoms in the last 6 months, and less than one half definitely intended to use
      condoms in the next month. Those who had used a condom at their most recent
      intercourse and those who intended to use a condom in the next month viewed the
      condom more favorably than others did. Intended condom use was associated with a
      perception of oral contraceptives as a less convenient method of birth control.

PMID- 8735163
TI  - Trends in chlamydia and other sexually transmitted diseases in a university
      health service.
AB  - The incidence of sexually transmitted diseases in a primarily student-based
      patient population served by a university health service was reviewed because of
      the perception that the number of positive chlamydia tests was declining. The
      most striking finding that emerged was that there was, indeed, a persistent and
      steady decline in the rates of chlamydia infection over the study time period of
      1989 to 1994. Other sexually transmitted diseases showed less definite declines
      or no significant change. The authors evaluated the number of positive chlamydia
      tests in the health service with symptoms suggestive of chlamydia infection. Of
      all university health service patients who tested positive for chlamydia, 48.8%
      were asymptomatic. A majority (75.2%) of the female patients who tested positive
      on their annual routine family-planning examination were also asymptomatic for
      chlamydia. Chlamydia-positive men presenting to the health service were far more
      likely to be symptomatic than were the women who were positive. Overall, a
      significant decrease in chlamydia occurred over the 5-year period in spite of an
      increasing enrollment, a fact that could perhaps be attributable to students'
      increased awareness of the risk of sexually transmitted infections and their use
      of condoms.

PMID- 8735164
TI  - An exploratory study of African American collegiate adult children of alcoholics.
AB  - The authors examined the relationship between students at a Black university who
      were adult children of alcoholics (ACOAs) and students who were not children of
      alcoholics (non-ACOAs) regarding levels of self-esteem, health in the family of
      origin, and social support during adolescence. The study participants were
      African American undergraduate students who responded to five surveys. The only
      significant relationship found was with results from the Michigan Alcoholism
      Screening Test (MAST). Level of drinking was significantly related to the self
      esteem of the ACOAs. A significant positive correlation between self-esteem and
      social support (mother) for the ACOAs and a negative correlation between self
      esteem and health in the family were also found. The findings are consistent with
      earlier reports in which an association was found between mother support and
      health of the family.

PMID- 8735165
TI  - Alcohol use among college students in Scotland compared with norms from the
      United States.
AB  - Four hundred fifty-six undergraduates at a Scottish university completed the Core
      Alcohol and Drug Survey, an instrument widely used in the United States to
      examine the nature, scope, and consequences of alcohol and other drug use on
      college campuses. The Scottish students were found to drink more frequently,
      consume more alcohol, and engage in binge drinking more often than their American
      counterparts. The Scottish students also demonstrated higher rates of hangovers,
      missed classes, and blackouts than the Americans, but the percentage of American
      students who had driven while intoxicated was greater than that of the Scots.
      Focus groups of students in Scotland and interviews with student affairs
      personnel and local officials indicated that student drinking is not generally
      viewed as a problem because extensive alcohol use appears to be part of Scottish
      culture and is readily accepted. Students reported that their drinking, other
      than in pubs, was spread out over time and was associated with eating and social
      activities. At student social events where alcohol was served, there was little
      evidence of loud, inappropriate, aggressive, or otherwise rowdy behavior;
      drinking appeared to be handled in a more controlled, safe, and responsible way
      than among US college students.

PMID- 8735166
TI  - College students' views on suicide.
AB  - College students were asked to rate the acceptability of suicide for themselves
      and for others in various circumstances. It was hypothesized that acceptability
      would vary as a function of circumstance of the suicide, the students' religious
      affiliation, history of past attempts, and whether the suicide was contemplated
      for oneself or another. The authors found that the highest acceptability for
      suicide was in the circumstances of terminal or chronic illness and depression.
      Students affiliated with organized religion were less accepting of suicide than
      were the individuals without such an affiliation. Previous suicide attempts were
      associated with greater acceptance of suicide for oneself or for others. In
      general, participants were more likely to accept suicide for others than for
      themselves, but the individuals who had previously attempted suicide displayed
      the opposite pattern under the circumstance of depression. Implications of these
      findings and directions for further research are discussed.

PMID- 8735167
TI  - An assessment of lower back pain in young adults: implications for college health
      education.
AB  - A convenience sample of 243 undergraduates completed a 36-item questionnaire on
      their knowledge about back care and exercise patterns before they attended
      lectures and a workshop on back mechanics. At the workshop, the students were
      individually evaluated for posture, hamstring flexibility, hip flexor
      flexibility, back and abdominal strength, and lifting technique. Twenty-nine
      percent of the students reported that they experienced no back pain; 71%
      experienced lower back pain 1 to 5 days a week. The majority were neglectful of
      their posture, lifting and carrying techniques, and scored fair-to-poor on the
      hamstring flexibility test, possibly foreshadowing back problems in later life.
      The majority of respondents were unsure of what exercises to do for back care.
      Within the subgroup of students who claimed they were knowledgeable about
      exercise, more than 50% were performing ineffective and potentially harmful
      exercises. The results underscored the potential worth of health education on
      back care offered through didactic instruction and experiential workshops.

PMID- 8735168
TI  - Factors influencing use of bicycle helmets among undergraduate students.
AB  - Undergraduate bicyclists' attitudes toward using helmets were surveyed, using a
      66-item questionnaire. The authors identified a series of factors that would
      increase the likelihood of students' using the protective devices and suggest
      interventions to be considered in developing programs to decrease morbidity and
      mortality in the bicycle-riding population.

PMID- 8735169
TI  - Helmet use among university bicyclists.
AB  - College-aged individuals are at risk for bicycle-related head injuries, but the
      risk of such injuries can be reduced by their use of bicycle helmets. The
      objective of this research was to measure the rate of bicycle helmet use by
      university bicyclists at a large public university in the southwestern United
      States at three different times. Bicyclists riding onto campus were observed as
      they rode through a main campus entrance in 1985, 1990, and 1994, and the
      percentage of bicyclists who were wearing a helmet was recorded. The bicyclists
      were unaware that their helmet use was being monitored. In 1985, 10% of
      bicyclists were wearing helmets; in 1990, only 4.4% wore helmets. In 1994, the
      proportion of helmet-wearing bicyclists had increased to 24%. Although the sample
      sizes were small, the 1994 increase was statistically significant. The reasons
      for the increase are unclear, and further study is needed to identify factors
      related to university bicyclists' use of bicycle helmets.

PMID- 8735170
TI  - Antihypertensive Drug Therapy. The effect of JNC criteria on prescribing patterns
      and patient status through the first year.
AB  - This study was designed to evaluate the impact of the protocol-driven
      antihypertensive therapy on outcomes guided by the Joint National Committee (JNC)
      on Detection, Evaluation, and Treatment of high blood pressure. In a systematic
      hypertension control program for union employees conducted in New York City,
      untreated patients who began treatment on monotherapy guided by JNC
      recommendations during three representative periods: I-pre-JNC IV (1986-1987); II
      post-JNC IV (1990-1991); and III (JNC V)-period of application of what were later
      published as JNC-V guidelines (1992) were observed during 1 year of treatment. A
      total of 550 presumably untreated patients were prescribed either diuretics, beta
      blockers, calcium channel blockers, or angiotensin converting enzyme inhibitors.
      There were 231 in period I, 213 in II, and 106 in III. The patient composition
      over time became more predominantly female and Hispanic (I to III: 28% to 34%,
      and 35% to 45%, respectively). The main outcome measures were type of drug first
      prescribed and the outcomes at the end of 1 year-changes in blood pressure,
      clinical chemistry measures and therapy, and clinic attendance are dropout rate.
      The pattern of first drug prescription changed from 85% to 90% of patients given
      diuretics or beta-blockers in I to 90% begun on calcium channel blockers or
      angiotensin converting enzyme inhibitors in II and finally, to an even
      distribution of drugs in III. Blood pressure response was similar across the
      three periods, 135/89 mm Hg (I), 138/89 (II), and 140/89 (III). Proportion of
      patients remaining on their initial drug in each period was fairly similar (60%,
      67%, and 69%). Scheduled clinic visits fell significantly from 7.4 visits in I,
      6.9 in II, and 6.4 in III (I upsilon III P = .004). Dropouts diminished
      significantly from 17% in I, to 10% in II, and 9% in III (I upsilon II or III P =
      .045). Modest positive changes in cholesterol and fasting blood sugar level
      occurred over time. In this general community setting, dramatic shifts in the
      choice of initial drug based upon application of JNC guidelines had little
      discernable impact on short term patient outcomes.

PMID- 8735171
TI  - Overtreatment of hypertension in the community?
AB  - Some patients currently receiving therapy for uncomplicated, mild to moderate
      essential hypertension may have been started on medication because of transient
      increases in office blood pressure (BP) or because of "white coat hypertension."
      As a consequence, many patients who do not have persistent hypertension may be
      receiving therapy for this diagnosis. This possibility was examined by
      discontinuing medication in 98 patients without target organ damage who were
      receiving longterm antihypertensive therapy under the care of their family
      physician in the community. Development of hypertension was based upon an
      increase in the patient's ambulatory BP (mm Hg) to > or = 160/95 recorded during
      usual daily activities. Evidence of early target organ damage was sought by using
      echocardiography to measure changes in left ventricular mass during the period
      off therapy. In the 50 patients who remained off treatment for 1 year, mean
      ambulatory BP increased (P < .001 from baseline (128 +/- 2/76 +/- 1) to 139 +/-
      1/82 +/- 1 at 1 year, but remained lower (P < .001) than corresponding office
      readings performed by the patient's family physician (baseline: 138 +/- 2/83 +/-
      1; 1 year: 150 +/- 2/89 +/- 1). At 1 year, ambulatory BP was < 150/90 and <
      140/90 in 41 and 21 patients, respectively. Withdrawal of therapy did not produce
      any changes in left ventricular mass index (g/m2) with the mean value at 1 year
      (104 +/-3) being similar to baseline (103 +/- 3). Of the remaining patients, 35
      redeveloped hypertension and 13 restarted therapy for reasons unrelated to BP.
      Many patients with treated, uncomplicated, mild to moderate hypertension may
      tolerate withdrawal of antihypertensive drug therapy without developing
      persistent hypertension or any increase in left ventricular mass.

PMID- 8735172
TI  - Evidence for amelioration of endothelial cell dysfunction by erythropoietin
      therapy in predialysis patients.
AB  - Evidence for the involvement of endothelial cells in the pathogenesis or
      erythropoietin-induced hypertension, and for endothelial cell damage in patients
      with chronic renal failure, has emerged and appears to be of major concern. We,
      therefore, investigated the effect of recombinant human erythropoietin (rHuEPO)
      therapy on endothelium-derived hormones in predialysis patients with progressive
      renal anemia. At the entry to the trial, the serum thrombomodulin concentration
      (Tm) and plasma endothelin-1 concentration (ET-1) in the predialysis patients
      were significantly higher than those in age- and sex-matched normal subjects.
      Following a 16 week period of treatment with 6000IU rHuEPO given intravenously
      once a week, patients' hematocrit increased from 27.1 +/- 2.6% to 34.6 +/- 3.2%
      (n = 16, P < .001). A positive correlation was found between Tm and serum
      creatinine concentration (Cr) (r = 0.61, P < .05 (n = 16), but no correlation was
      found between ET-1 and Cr. Tm and Tm/Cr significantly decreased from 7.9 +/- 2.8
      ng/mL to 6.6 +/- 2.4 ng/mL (P < .01, n = 16), and from 2.1 +/- 0.7 (x10(-10) to
      1.6 +/- 0.7 (x10(-10), P < .01, n = 16), respectively. However, there was no
      change in ET-1 as a result of the rHuEPO therapy. Creatinine clearance (Ccr), Cr,
      total amount of daily Tm excretion, Tm clearance/Ccr, daily urinary protein and
      albumin excretion, and blood pressure also remained unchanged throughout the
      trail. The present study indicates that correcting anemia by rHuEPO therapy
      reduces an abnormally elevated Tm in predialysis patients while blood pressure
      and renal function remain unchanged, suggesting that rHuEPO has a beneficial
      effect on endothelial cell dysfunction in chronic renal failure patients. This
      effect may be mediated via an improved oxygen supply to the endothelial cells due
      to the amelioration of anemia by rHuEPO.

PMID- 8735173
TI  - Relaxant effect of human brain natriuretic peptide on human artery and vein
      tissue.
AB  - Brain natriuretic peptide (BNP) is a cardiac-derived peptide hormone with
      cardiovascular and renal actions that is structurally and functionally related to
      atrial natriuretic peptide (ANP). Previous studies using rat vascular tissue have
      demonstrated a direct vasorelaxant effect of BNP. However, species-specific
      potency issues have precluded an accurate measurement of the effect of human BNP.
      This report demonstrates the vasorelaxant effects of human BNP on human vascular
      tissue prepared from internal mammary artery and saphenous vein samples. The
      vasorelaxant effect of human BNP is compared to the other members of the
      natriuretic peptide family, human ANP and C-type natriuretic peptide (CNP). With
      regard to potency and magnitude of effect, human BNP and human ANP were similar
      in relaxing arterial tissue preconstricted with endothelin-1 (BNP ED50 = 1.9
      nmol/L and ANP ED50 = 1.8 nmol/L) or phenylephrine (BNP ED50 = 10 nmol/L and ANP
      ED50 = 19 nmol/L), while CNP was significantly less effective. All three
      natriuretic peptides exhibited weak venodilating action. These data demonstrate
      that human BNP is a potent inhibitor of the vasoconstrictive actions of
      endothelin-1 and the alpha-adrenergic agonist phenylephrine on isolated human
      artery tissue preparations.

PMID- 8735174
TI  - Terazosin: ex vivo and in vitro platelet aggregation effects in patients with
      arterial hypertension.
AB  - Antihypertensive effect, platelet aggregation, and plasma lipid profile were
      studied in a group of 14 hypertensive patients with diastolic blood pressure
      between 96 and 116 mm Hg during placebo and terazosin phases. Terazosin, an alpha
      1-adrenergic blocking agent, was given initially at the dosage of 1 mg daily.
      Then it was continued at a dosage of 2 mg daily and 5 mg daily respectively, each
      dosage for 4 weeks. Blood pressure was taken every 2 weeks. Ex vivo platelet
      aggregation induced by epinephrine, collagen, and adenosine diphosphate (ADP)
      were carried out twice during the first placebo phase, once at the end of each
      terazosin dosage, and once in the second placebo phase. Total cholesterol, HDL
      cholesterol, and triglycerides were measured at the end of first placebo and
      terazosin phases. Blood from eight patients was taken during the second placebo
      phase to carry out in vitro response of platelet aggregation induced by ADP,
      collagen, and epinephrine before and after incubation with terazosin (1, 2 and 5
      micrograms/L or doxazosin (100, 200, and 500 micrograms/L for 5 min. Terazosin
      induced a statistically significant decrease in 14.2/8.0 mm Hg, 26.1/13.4 mm Hg,
      and 33.9/16.5 mm Hg in the supine position for 1, 2, and 5 mg/daily,
      respectively. No changes in heart rate were observed. Terazosin inhibited
      significant ex vivo platelet aggregation induced by epinephrine, collagen, and
      ADP in a range from 20% to 45% for different concentrations of inducers.
      Reductions in platelet aggregation seemed not to be dose dependent, as reductions
      were statistically equivalent for dosages of 1, 2, and 5 mg daily. Terazosin
      significantly reduced the level of total cholesterol (8.71%) and triglycerides
      (14.31%), and increased (although not significantly) levels of HDL cholesterol
      (3.91%). In vitro platelet aggregation was inhibited by doxazosin to a
      significant extent but not by terazosin.

PMID- 8735175
TI  - Alpha-blockade and thiazide treatment of hypertension. A double-blind randomized
      trail comparing doxazosin and hydrochlorothiazide.
AB  - This trial involved 107 patients in a two-group, parallel, double-blind,
      randomized study comparing the diuretic, hydrochlorothiazide (HCTZ) (dose 25 to
      50 mg) and the alpha 1 antagonist, doxazosin (dose 2 to 16 mg). All randomized
      participants were followed for at least 1 year. Participants were recruited from
      the community. The study was carried out in four phases: Phase I-Baseline; Phase
      II-Monotherapy Titration; Phase III-Combination Therapy Titration; and Phase IV
      Maintenance. The following measures were carried out: blood pressure,
      biochemistries, lipids/lipoproteins, quality of life, ambulatory
      electrocardiograms, echocardiograms, adverse experiences, and drug adherence.
      Both drugs were well tolerated, with only 4% taken off doxazosin and 7% off HCTZ.
      Adverse experiences were uncommon and mostly mild. Both drugs were effective in
      managing hypertension over 1 year of therapy. There was no difference noted in
      terms of efficacy of blood pressure lowering between the two study drugs, nor was
      there any evidence of tolerance developing or of any serious adverse effects.
      Average final doses for drugs were 7.8 mg for doxazosin and 36 mg for HCTZ. The
      results show that, over the course of 1 year, both drugs significantly lowered
      systolic and diastolic pressures compared to baseline; doxazosin (-19 and -16 mm
      Hg); HCTZ (-22 and 15 mm Hg). Blood pressure lowering was not significantly
      different between drugs. Sitting heart rate was not affected by drugs. Changes in
      quality of life measures were similar between groups. Echocardiographic measures
      at 1 year showed significant between-drug differences in change in left internal
      end systolic and diastolic dimensions and end systolic stress. Both doxazosin and
      HCTZ were effective drugs over 1 year for treating hypertension.

PMID- 8735176
TI  - Relationship of steady state and ambulatory blood pressure variability to left
      ventricular mass and urinary albumin excretion in essential hypertension.
AB  - A relationship exists between blood pressure and cardiovascular morbidity and
      mortality. Recent data suggest that the variability of blood pressure is also
      related to hypertensive target organ damage. We studied the relationship of
      ambulatory daytime and night-time and supine beat-to-beat Finapres blood pressure
      variability to left ventricular mass index (LVMI) and urinary albumin excretion
      (albumin/creatinine ration: ACR) in 33 hypertensive patients, untreated for more
      than 3 months. In a multiple stepwise regression model the strongest relationship
      with the LVMI existed for night-time systolic pressure (R = 0.46, multiple
      regression coefficient: 0.90 +/- 0.26 P < .01) and daytime diastolic blood
      pressure variability (multiple R increased to 0.60, multiple regression
      coefficient 3.16 +/- 1.18, P < .05). Log ACR had the strongest relationship to
      ambulatory systolic daytime pressure (R = 0.40, multiple regression coefficient
      0.0093 +/- 0.0040, P < .05) and the variability of diastolic Finapres blood
      pressure (multiple R increased to 0.52, multiple regression coefficient 0.081 +/-
      0.0036, P < .05). Both ambulatory and steady state blood pressure variability are
      related to early hypertensive target organ damage. This relationship exists
      independent of the height of blood pressure .

PMID- 8735177
TI  - Age-related and vasomotor stimuli-induced changes in renal vascular resistance
      detected by Doppler ultrasound.
AB  - Indirect measurement of renal vascular resistance by duplex Doppler waveform
      analysis was evaluated in relation to aging and some pathophysiological
      conditions. Baseline renal resistive index (RRI) (peak systolic frequency shift -
      lowest diastolic frequency shift/peak systolic frequency shift) was measured in
      healthy controls aged 20 to 85 years by analyzing the blood flow velocity
      waveform of interlobar arteries. RRI changes induced by sympathetic activation
      (cold pressor test and handgrip test) or by fluid load were evaluated. Both
      repeatability and reproducibility were very good, as the intra and interoperator
      variations were all less than their reproducibility coefficients. RRI showed a
      significant increase with aging (ANOVA P < .001), particularly evident in
      subjects older than 50 years. Both the cold pressor test and handgrip test
      induced in all the subjects (n = 16) a significant increase in RRI (P < .001),
      from 0.59 +/- 0.04 to 0.69 +/- 0.04 (12 +/- 6%) for the cold pressor test and
      from 0.57 +/- 0.03 to 0.66 +/- 0.03 (15 +/- 2%) for the handgrip test. In eight
      subjects intravenous fluid load (0.25 mL/kg/min of 0.9% NaCl for 120 min) caused
      a significant decrease in RRI (P < .001), from 0.62 +/- 0.02 to 0.53 +/- 0.01 (17
      +/- 2%), which was inversely related to mean blood pressure rise (r = 0.71, P <
      .001). These data show that pulsed wave Doppler analysis is an accurate method
      for an indirect evaluation of changes in renal vascular resistance induced by
      common vasomotor stimuli.

PMID- 8735178
TI  - Three-dimensional echocardiography compared to two-dimensional echocardiography
      for measurement of left ventricular mass anatomic validation in an open chest
      canine model.
AB  - A three-dimensional echocardiographic system has been developed that can
      accurately compute left ventricular mass in vitro. This study was designed to
      validate the new echocardiographic system for the measurement of left ventricular
      mass in vivo and to compare the accuracy of three-dimensional echocardiography to
      the accuracy of conventional two-dimensional echocardiography for measuring left
      ventricular mass. Echocardiographic imaging was performed 6 h following coronary
      ligation in 20 open chest dogs, at which time the heart was excised and the left
      ventricle weighed. Three-dimensional echocardiography used multiple short axis
      sections and polyhedral surface reconstruction to compute myocardial volume. The
      two dimensional methods employed the truncated ellipsoid model and the area
      length model. Myocardial volume was multiplied by 1.05 g/cc and echocardiographic
      mass estimates were compared to the true left ventricular weight. Three
      dimensional echocardiography provided the best correlation (r = 0.96, upsilon r =
      0.88 and r = 0.83 for the truncated-ellipsoid and area-length methods,
      respectively), and the lowest standard error of the estimate for the regression
      equation (+/- 5.5 g upsilon +/- 11.0 and +/- 14.6 g, respectively). Three
      dimensional echocardiography also had the lowest standard deviation for the echo
      true mass differences (+/- 5.8 g upsilon +/- 10.7 g and +/- 14.2 g) and a lower
      root mean square percent error (6.8%) upsilon 12.6% and 12.7%). In this open
      chest canine model, three-dimensional echocardiography is more accurate than
      standard two-dimensional echocardiographic methods for measuring left ventricular
      mass.

PMID- 8735179
TI  - Characterization of endothelium-dependent vasodilation and vasoconstriction in
      coronary arteries from spontaneously hypertensive rats.
AB  - Coronary artery disease often occurs in patients with hypertension. The present
      study was designed to evaluate coronary vascular function in isolated coronary
      arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats and
      to determine the effect of antihypertensive treatment on coronary vascular
      responsiveness. Male SHR and WKY rats (12 to 14 weeks old) were divided into
      control and hydralazine-treated (120 mg/L drinking water for 10 days) groups.
      After 10 days, arterial pressure and heart rate were recorded while rats were
      conscious and unrestrained. Left ventricular coronary arteries (200 to 300
      microns diameter) were isolated and intraluminal diameter was continuously
      recorded while vessels were maintained at a constant intraluminal pressure of 40
      mm Hg. Relaxation of coronary arteries to both acetylcholine and nitroprusside
      was slightly, but significantly, enhanced in vessels from SHR compared to WKY
      rats. The enhanced relaxation was a specific effect, since isoproterenol induced
      similar relaxation in coronary arteries from SHR and WKY rats. Contraction to
      phenylephrine, but not endothelin-1, was augmented in coronary arteries from SHR
      compared to WKY rats. Treatment with hydralazine significantly lowered arterial
      pressure in SHR and WKY rats, but did not alter the enhanced contraction to
      phenylephrine or the enhanced relaxation to acetylcholine and nitroprusside in
      coronary arteris from SHR. These results indicate that coronary arteries of 12 to
      14 week-old SHR do not have impaired endothelium-dependent relaxation, but to
      exhibit enhanced alpha-adrenoceptor-mediated contraction that is not reduced by
      lowering arterial pressure.

PMID- 8735180
TI  - Impaired fibrinolysis and insulin resistance in patients with hypertension.
AB  - Plasma plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen
      activator (tPA) antigens and activities were measured in 28 patients with
      hypertension and 12 normal controls. Steady state plasma glucose (SSPG)
      concentrations were also determined after an infusion of somatostatin, insulin
      and glucose. Patients with hypertension were further subdivided into two groups:
      insulin resistance (SSPG > 190 mg/dL, n = 14) and no insulin resistance (SSPG <
      190 mg/dL, n = 14). As compared to normal controls, hypertensive patients, either
      with or without insulin resistance, had a significant (P < .005) increases in PAI
      1 activity (18.6 +/- 1.3 upsilon 8.1 +/- 0.8 IU/mL), PAI-1 antigen (31.1 +/- 2.0
      upsilon 12.7 +/- 0.9 ng/mL) and tPA antigen (15.5 +/- 0.9 upsilon 8.8 +/- 0.9
      ng/mL), and significant decrease in tPA activity (0.43 +/- 0.05 upsilon 1.02 +/-
      0.16 IU/mL) than normotensive controls. Furthermore, hypertensive patients with
      insulin resistance had significantly higher PAI-1 activity (22.0 +/- 2.2 upsilon
      15.3 +/- 0.8 IU/mL, P = .006) and tPA antigen (17.4 +/- 1.2 upsilon 13.6 +/- 1.3
      ng/mL, P = .02) than did hypertensive patients without insulin resistance.
      However, PAI-1 antigen was insignificantly higher (34.1 +/- 2.9 upsilon 28.1 +/-
      2.4 ng/mL, P = .06) and tPA activity insignificantly lower (0.42 +/- 0.08 upsilon
      0.43 +/- 0.08 IU/mL, P = .47) in hypertensive patients with insulin resistance
      than in those without insulin resistance. In addition, PAI-1 activity and tPA
      antigen were significantly correlated with blood pressure, SSPG, triglyceride,
      HDL-cholesterol and integrated glucose response to an oral load of 75 g glucose.
      Thus, patients with hypertension have impaired fibrinolytic activity due to
      increased PAI-1 when compared to normotensive controls, and the magnitude of this
      fibrinolytic defect is greater in hypertensive patients who have insulin
      resistance. Insulin resistance with associated metabolic abnormalities may be one
      of the causes for impaired fibrinolysis in hypertension.

PMID- 8735182
TI  - Effects of a restricted sleep regimen on ambulatory blood pressure monitoring in
      normotensive subjects.
AB  - The influence of sleep deprivation during the first part of the night on 24-h
      ambulatory blood pressure monitoring (ABPM) was studied in 18 normotensive
      subjects. They underwent two ABPM, one week apart: during the first, they slept
      from 11 PM to 7 AM, and during the second, from 2 AM to 7 AM. The main
      differences were observed at dawn, before awakening, when SBP and DBP
      significantly decreased (P < .01) in the restricted sleep regimen, and during the
      morning after the recovery sleep, when SBP and HR significantly increased (P <
      .05). The explanation for these findings is not obvious. We suppose that the
      decrease in SBP and DBP at dawn might be due to a reorganization of the sleep
      phases in the restricted sleep regimen, whereas the increase in SBP and HR after
      awakening might be due to a greater sympathetic activation, as though sleep
      deprivation was a stressful condition.

PMID- 8735181
TI  - Specific prorenin/renin binding (ProBP). Identification and characterization of a
      novel membrane site.
AB  - Renin can be detected in cardiovascular and other tissues but it disappears after
      bilateral nephrectomy indicating that tissues can take up or bind renal renin
      from the circulation. If renin uptake is the result of specific binding, plasma
      prorenin may be a natural antagonist of tissue directed renin-angiotensin
      systems. To investigate if specific prorenin/renin uptake occurs in rat tissues,
      binding studies were performed, with rat microsomal membrane preparations using
      recombinant rat prorenin metabolically labeled with 35S-methionine as a probe. A
      high affinity binding site for both renin and prorenin was identified. Affinities
      for prorenin and renin were approximately 200 and 900 pmol/L, respectively.
      Binding was reversible, saturable, and pH and temperature dependent. The relative
      binding capacities of membranes from various rat tissues were as follows
      (fmol/mg): renal cortex (55), liver (54), testis (63), lung (31), brain (18),
      renal medulla (15), adrenal (17), aorta (7), heart (4), and skeletal muscle (1).
      Bound prorenin was displaced by rat and human renin or prorenin but not by the
      prosequence of rat prorenin, angiotensin I or II, rat or human angiotensinogen,
      the renin inhibitor SQ30697, atrial natriuretic factor, amylase, insulin, bovine
      serum albumin, hemoglobin, heparin, lysozyme, ovalbumin, cytochrome C, pepsin,
      pepsinogen, ribonuclease A, mannose-6-phosphate, alpha-methyl mannoside,
      gonadotropin releasing hormone, or an antibody to hog renin binding protein.
      these results demonstrate specific binding of prorenin to a site in rat tissues,
      herein named ProBP, that also binds renin. It is possible that differences in
      prorenin/renin binding capacity determine the activity of tissue-directed renin
      angiotensin systems and that prorenin is a natural antagonist. Alternatively, a
      prorenin/renin receptor may have been identified that may function by transducing
      an intracellular signal.

PMID- 8735183
TI  - The hypertensive Ren-2 transgenic rat TGR (mREN2)27 in hypertension research.
      Characteristics and functional aspects.
AB  - Primary human hypertension is a polygenic disorder. It is the prevalent cause of
      cardiovascular disease leading to cardiac failure, stroke, chronic renal failure
      and, ultimately to death. Several genes are involved in cardiovascular control
      mechanisms and their genetics are complex. Experimental models which are well
      defined are needed to clarify the role of individual genes. The generation of the
      hypertensive transgenic rat line TGR (mREN2)27 bearing the murine Ren-2 gene
      cloned from the DBA/2J mouse strain provides a monogenic model of hypertension in
      which the genetic basis (the additional renin gene) is known. These rats develop
      severe hypertension, which reaches 200 mm Hg and higher at 8 weeks of age in the
      heterozygous animal. Homozygous rats develop even higher blood pressures than
      heterozygous animals, which is paralleled by a higher mortality rate in
      homozygous rats. Animals develop pathomorphologic alterations which are
      characteristic for systemic hypertension. The transgenic rats are characterized
      by unchanged or even suppressed concentrations of active renin, angiotensin I
      (ANG I), ANG II, and angiotensinogen compared to transgene-negative littermates.
      In contrast, plasma levels of inactive renin (prorenin) are much higher in TGR
      (mREN)27 rats than in control animals. In the kidneys, renin is suppressed,
      probably mediated through negative feedback inhibition, in other tissues,
      especially in the adrenal gland, murine Ren-2 mRNA is expressed at very high
      levels. The cascade of pathophysiologic events which finally lead to hypertension
      is not fully understood in this rat model. Treatment with ACE inhibitors or
      angiotensin II receptor antagonists such as losartan is extremely efficient,
      which could mean that hypertension in this model is mediated through ANG II.
      Since the the renin-angiotensin system (RAS) in the kidneys is suppressed, other
      ANG II generating sites must be considered. This favors the concept of extrarenal
      RASs in this model.

PMID- 8735184
TI  - Monitoring and management of antihypertensive therapy induced deterioration in
      acute ischemic stroke.

PMID- 8735185
TI  - Detection of the angiotensin converting enzyme gene I/D polymorphism from
      extremely small volumes of stored serum.

PMID- 8735186
TI  - Digoxin-like immunoactivity in pregnant women with diabetes mellitus.

PMID- 8735187
TI  - Prostaglandin E1 with phentolamine for the treatment of erectile dysfunction.
AB  - AIM OF THE STUDY: to evaluate the feasibility of a self-injection programme for
      impotence with a combination of 10 micrograms prostaglandine E1 (PGE1) and 0.5 mg
      phentolamine. METHOD: follow-up at outpatients department with history taking,
      physical examination and questionnaires of 58 patients using this combination.
      Many patients could compare this drug combination with previously used drugs for
      intracavernous use. RESULTS: 42 patients started regular use. After a follow-up
      of 14 months, 26 are still on the programme. Drug related problems encountered:
      10 patients reported insufficient erectile response, five patients have had
      priapism, four patients experienced severe pain, one patient developed fibrosis.
      CONCLUSION: the combination of PGE1 and phentolamine is very effective. The
      complication rate is comparable with those reported from PGE1 alone and from
      papaverine with phentolamine.

PMID- 8735188
TI  - Determinants of satisfactory rigidity after intracavernosal injection with
      prostaglandin E1 in men with erectile failure.
AB  - The study examines the erectile response of intracavernosal injection with
      increasing doses of prostaglandin E1 (PGE) and papaverine/phentolamine (PP) in
      516 men with erectile failure. The response was correlated to age, the duration
      of erectile failure, the quality of spontaneous erections, tobacco consumption
      and medicine use. In addition, the erectile response was related to penile
      brachial index (PBI) the free testosterone index and various hormonal parameters.
      Over 60% of the subjects obtained satisfactory rigidity of at least 30 min
      duration with 7-15 micrograms PGE. A further 15% (PGE non-responders at the doses
      tested) obtained rigidity with PP. The average dose necessary to achieve rigidity
      was 8.8 micrograms for PGE and 0.94 ml (papaverine: 15 mg/ml; phentolamine 0.5
      mg/ml) for PP. The average duration of rigidity was 2.2 h and 2.3 h for PGE and
      PP, respectively. Tobacco consumption, the duration of erectile failure and the
      age of the subject did not influence the response to intracavernosal injection.
      Moreover the PBI, the free testosterone index or libido of the subject, did not
      appear to be generally important for obtaining satisfactory rigidity. In
      contrast, chronic medication, especially antihypertensive drugs, was associated
      with significantly higher numbers of poor responders, a shorter duration of
      erection in the responders and higher doses of PGE necessary to achieve a
      satisfactory response. The combination of increasing age and antihypertensive
      medication was predictive for a poor intracavernosal response. In general, a
      reduced incidence of morning erections was predictive of a weaker response to
      PGE. The proportion of men with a PBI lower than 0.75 increased with age. These
      subjects more often took chronic medication, had a lower frequency of morning
      erections and exhibited a significantly weaker reaction to PGE than subjects with
      higher PBI. In summary, a large number of men with erectile failure can obtain
      satisfactory rigidity with intracavernosal injection. In men taking
      antihypertensive medication, especially in higher age groups, the dose of the
      intracavernosal medication had to be increased. A reduced sensitivity to
      intracavernosal medication could be predicted from a lower PBI and a reduced
      frequency of spontaneous erections.

PMID- 8735189
TI  - Endothelin-1-induced modulation of contractile responses elicited by an alpha 1
      adrenergic agonist on human corpus cavernosum smooth muscle.
AB  - The goal of these studies was to examine endothelin-1 (ET-1)-induced modulation
      of contractile responses elicited by the selective alpha 1-adrenergic agonist,
      phenylephrine (PE), on isolated human corporal tissue strips. Pharmacological
      studies were conducted on human corporal tissue strips obtained from 22 patients
      undergoing implantation of penile prostheses for erectile dysfunction. For the
      purposes of statistical analysis, the patients were stratified into two age
      groups: A, age < or = 59 y (n = 10) and B, age > or = 60 y (n = 12). The patients
      were further sub-divided into two diagnostic categories, diabetics (DM, n = 9)
      and nondiabetics (ND, n = 13). Cumulative concentration-response curves (CRCs)
      were constructed to the alpha 1-adrenergic agonist, PE, prior to constructing a
      CRC to a single mixture of PE and ET-1 on the same tissue. A previously described
      fixed molar ratio (FMR) protocol was used to generate CRCs to mixtures of PE and
      ET-1. In all cases, for the PE:ET-1 FMRs of 90:10, 80:20 and 70:30, the partial
      substitution of PE with ET-1 resulted in an approx 3-fold leftward shift in the
      EC50 of the PE alone CRC with an approx 4% concomitant increase in Emax and a
      decrease in the slope factor value. There were no significant age- or disease
      related differences in any of the logistic parameter estimates that describe the
      FMR CRC, indicating that there are no detectable age- or disease-related
      alterations in ET-1-induced amplification of alpha 1-adrenergic-mediated
      contractions in these studies. In addition, the location of the FMR CRC was
      precisely predicted by the theoretical CRC for simple additivity of agonist
      effects. In conclusion, since relatively small increases in ET-1 concentrations
      were associated with significant increases in alpha 1-adrenergic-mediated
      contractile responses, these data provide further testimony to the importance of
      ET-1 in modulating corporal smooth muscle tone, and moreover, establish a
      conceptual framework for understanding the mechanism of its action(s).

PMID- 8735190
TI  - Should venous surgery be still proposed or neglected?
AB  - Forty-four men aged 20-56 years (mean 42) complaining a venous erectile
      dysfunction underwent penile venous surgery. Fifteen patients (34.1%) were
      treated by DDVL, 29 cases (65.9%) underwent DDVL + corporopexy. All patients were
      followed-up at short and long-term periods. In short-term follow-up, eight
      patients (57.2%) of 15 treated by DDVL showed spontaneous erection, six patients
      (42.8%) showed persistent erectile dysfunction. In long-term follow-up, four
      patients of this group (28.6%) showed spontaneous erection. The others, 10
      patients (71.4%), were then treated by other therapeutical alternatives. Twenty
      two patients (75.8%) of 29 operated with DDVL + corporopexy showed spontaneous
      erection in short-term follow-up. After one year, in long-term follow-up, whereas
      total 15 patients (51.7%) of them were obtaining full erection, the others
      required other forms of treatments. In both groups in a long-term follow-up,
      total 19 patients of 43 (44.2%) showed full spontaneous erection, four patients
      (9.3%) needed intracavernous injection and six patients (13.9%) were treated with
      penile prosthetic implants. A total of 29 patients (67.4%) were able to have
      acceptable sexual intercourse. We concluded that venous surgery is still useful
      in selected patients having no better therapeutical alternatives.

PMID- 8735191
TI  - Sites of androgenic regulation of cavernosal blood pressure during penile
      erection in the rat.
AB  - The present studies were designed to determine the role of reactive vascular
      smooth muscle in the regulation of blood flow into and out of the cavernous
      sinuses during penile erection in castrated and testosterone-treated animals.
      While the mean arterial pressure and intracavernosal pressure were continuously
      monitored, vasoactive drugs were injected into the aorta or into the cavernous
      sinuses during erection. The results show that both a NO releasing vasodilatory
      drug and an alpha adrenergic agonist significantly affected both mean arterial
      pressure and intracavernosal pressure when injected into the aorta. However, when
      these same drugs were injected into the cavernous sinuses, neither drug exerted a
      significant influence on the erectile response. Based on these studies, we
      conclude that the flow of blood into the cavernous sinuses during erection is
      regulated by reactive vascular smooth muscle but the outflow is not under the
      regulation of reactive vascular smooth muscle. Furthermore, the relaxation of the
      smooth muscle which controls the flow of blood into the cavernous sinuses during
      erection may be under partial androgenic control.

PMID- 8735192
TI  - Coronary artery bypass graft surgery and its impact on erectile function: a
      preliminary retrospective study.
AB  - Erectile function is markedly affected by acute alterations in circulatory
      homeostasis of which coronary artery bypass graft surgery is an excellent model.
      A group of consecutive patients who had undergone coronary artery bypass surgery
      6-12 months previously were selected for detailed review by questionnaires that
      scored their pre-operative and post-operative sexual function and erectile
      ability and aspects of the quality of life. Thirty patients were evaluable. 10
      men (33.3%) had poor erectile function before surgery. Eleven out of 30 men
      reported an improvement in erectile function while 10 men experienced a decrease
      or cessation of erectile function. Four of the five patients reporting new post
      operative erectile function had had good pre-operative function suggesting that
      the surgery was directly associated with the impotence in these men. This pilot
      study suggests that coronary artery bypass surgery can have a significant impact
      in erectile function.

PMID- 8735193
TI  - A simple, reliable method for the determination of chlorinated volatile organics
      in human breath and air using glass sampling tubes.
AB  - A method for determining chloroform, 1,1,1-trichloroethane, carbon tetrachloride,
      and trichloroethene in breath samples was developed. It consisted of collecting
      samples in 40-ml. glass-silanized tubes that were 16-in. long and had a 0.64-in.
      diameter. The ends tapered, resulting in a tube with a 1/4-in. diameter that was
      1 3/4-in. long; each end had a shutoff valve attached. One end had a strip of
      rubber tube attached to the shutoff valve for collecting the breath sample, and
      the other end contained a 1/4-in. Swagelok nut with a rubber septum for
      withdrawing the sample. Samples were withdrawn using a pressure-lock, gastight
      syringe, and they were injected onto a gas chromatograph fitted with an electron
      capture detector. The analytes were stable for at least 22 days in these tubes.
      The method detection limit was determined to be 0.03, 0.08, 0.04, and 0.04 pg/ml.
      for chloroform, 1,1,1-trichloroethane, carbon tetrachloride, and trichloroethene,
      respectively. Precision, based on 13 injections, was determined to be 13% for
      0.09 pg chloroform, 13% for 0.21 pg 1,1,1-trichloroethane, 8% for 0.16 pg carbon
      tetrachloride, and 14% for 0.1 pg trichloroethene. In all, the proposed method is
      a sensitive and reliable one for determining volatile organic compounds in breath
      and a method that can also be applied to air sampling.

PMID- 8735194
TI  - Gas chromatographic determination of parathion and paraoxon in fish plasma and
      tissues.
AB  - A sensitive capillary gas chromatographic (GC) method for the simultaneous
      determination of the organophosphate insecticide, parathion, and its active
      metabolite, paraoxon, in biological samples was developed. This method involved a
      simple liquid-liquid extraction of parathion and paraoxon from water, plasma, or
      tissues and capillary GC determination using electron-capture detection and
      splitless injection; malathion was used as the internal standard. A gradient oven
      temperature program was used; the injection port and detector temperatures were
      200 and 300 degrees C, respectively. These techniques allowed quantitative
      determination of parathion and paraoxon at 9-210-ng/ml. concentrations;recoveries
      ranged from 79.4 to 110.3% for tissues and from 91.9 to 100.0% for plasma and
      water. The within-day and between-day coefficients of variation were less than
      8.0%. The method was used to characterize the pharmacokinetics of parathion and
      paraoxon and the tissue distribution of paraoxon in rainbow trout.

PMID- 8735195
TI  - Fatal zipeprol and dextromethorphan poisonings in Korea.
AB  - Zipeprol and dextromethorphan are abused together by young people in Korea to
      obtain a stronger hallucinogenic effect. Because large amounts of these drugs are
      taken for this reason, nine fatal poisonings due to zipeprol and dextromethorphan
      have been reported since 1993. In this paper, the concentration of drugs in the
      postmortem blood and gastric contents of these victims is examined. The
      determination and identification of the drugs in biological fluids were conducted
      by gas chromatography (GC)-thermionic specific detection and GC-mass
      spectrometry. Linear calibration curves and high recoveries were obtained. The
      blood concentrations of zipeprol varied from 1.3 to 28.6 micrograms/mL, and the
      concentrations of dextromethorphan ranged from 1.1 to 18.3 micrograms/mL. The
      concentration of zipeprol in the gastric contents ranged from 26.8 to 1384.8
      micrograms/g, and dextromethorphan concentrations varied from 2.1 to 243.7
      micrograms/g.

PMID- 8735196
TI  - Quantitative gas chromatographic analysis of 3-cyano-3,3-diphenylpropionic acid,
      the acidic metabolite of bezitramide (Burgodin), in urine.
AB  - A sensitive gas chromatographic procedure with nitrogen-phosphorus detection was
      developed for the quantitative determination of 3-cyano-3,3-diphenylpropionic
      acid, the acidic metabolite of the narcotic analgesic bezitramide (Burgodin). Gas
      chromatography with mass spectrometric detection was used for confirmation. An
      internal standard, 5-cyano-5,5-diphenylvaleric acid, was synthesized and purified
      in our laboratory. The compound was extracted from 5 mL of hydrolyzed urine with
      n-hexane-ethyl acetate (85:15, v/v). Derivatization of the extract with an
      ethereal diazomethane solution was performed immediately before chromatographic
      analysis. Under the described conditions, the quantitation limit for 3-cyano-3, 3
      diphenylpropionic acid in urine was 10 ng/mL. The extraction recovery was 82%.
      The calibration graph was linear over the concentration range from 10 to 500
      ng/mL; at a 100-ng/mL concentration, within-day and day-to-day percent
      coefficients of variation of 1.9 and 3.7%, respectively, were obtained. Urine
      samples from 16 persons suspected of using bezitramide were analyzed, and they
      revealed metabolite concentrations that ranged from 10.5 to 88 ng/mL.

PMID- 8735197
TI  - Cross-reactivity of stimulants found in sports drug testing by two fluorescence
      polarization immunoassays.
AB  - We investigated the usefulness of immunological methods for presumptive detection
      of stimulants found in sports drug testing. The ingestion of substances that show
      no cross-reactivity in tests commercially available for the detection of
      amphetamines can produce positive results in the urine. Human metabolism
      contributes to the positive results of some urine samples when the parent
      compound does not cross-react with the antibodies of the assay. Urine samples
      from healthy volunteers given stimulants were tested by chromatographic methods
      and by two different fluorescence polarization immunoassays (FPIA) from Abbott
      Laboratories for the analysis of amphetamines. According to the results obtained,
      we classified stimulants into four groups: detectable stimulants that gave rise
      to amphetamine by human metabolism (group 1); detectable ephedrines and related
      compounds, appearing in the urine either as parent compounds or originated by
      metabolism (group 2); detectable stimulants that displayed actual cross
      reactivity with amphetamine tests (group 3); and stimulants not detected by FPIA
      (group 4). Most of the true doping cases due to the ingestion of stimulants may
      be detected by FPIA. The specificity of the results may be increased by combining
      immunological assays with different antibodies.

PMID- 8735198
TI  - Comparison of ethanol concentrations in blood, serum, and blood cells for
      forensic application.
AB  - Ethanol concentrations in serum (SAC) and whole blood (BAC) were determined for
      235 subjects by a headspace gas chromatographic method. The SAC:BAC ratios ranged
      between 1.04 and 1.26. The mean was 1.14, and the normal distribution had a
      standard deviation (SD) of 0.041. When a conversion (division) factor for SAC to
      BAC of 1.18 (mean + 1 SD) was used, 84% of estimated BACs were less than that
      measured; the remaining estimates differed by less than 7 mg/dL. An SAC greater
      than 100 mg/dL reliably indicated a BAC of more than 80 mg/dL. Ethanol
      concentrations in blood cells (CAC) were similarly determined for 167 of these
      subjects. The CAC:BAC ratios ranged from 0.66 to 1.00 and had a mean of 0.865 and
      a negatively skewed normal distribution with an SD of 0.065. When a conversion
      (division) factor for CAC to BAC of 0.93 (mean + 1 SD) was used, 89% of estimated
      BACs were less than that measured; the remaining estimates differed by less than
      8 mg/dL. A CAC greater than 80 mg/dL reliably indicated a BAC of more than 80
      mg/dL. The CAC is useful in forensic practice when either blood or serum is not
      available.

PMID- 8735199
TI  - Analysis of benzoylecgonine in dried blood spots by liquid chromatography-
      atmospheric pressure chemical ionization tandem mass spectrometry.
AB  - Residual samples from blood spots (i.e., whole blood spotted onto filter paper)
      are a useful source for epidemiological screening studies involving newborns.
      However, the small volume of blood available from residual blood spots
      complicates the assay. A method for analyzing benzoylecgonine (BZE; the primary
      metabolite of cocaine) in blood spots, in which the blood spot is eluted with
      aqueous ammonium acetate-methanol containing N-methyl trideuterated-BZE as an
      internal standard, followed by high-performance liquid chromatography-atmospheric
      pressure chemical ionization tandem mass spectrometry using multiple reaction
      monitoring, has been developed. This approach provides a rapid, direct, sensitive
      (limit of detection, approximately 2 ng/mL, based on a 12-microL sample size),
      and highly specific means of determining BZE concentrations in blood spots. We
      have applied this method for confirmatory analyses in a large epidemiological
      study of the prevalence of cocaine use during late pregnancy.

PMID- 8735200
TI  - Evaluation of an HPTLC method for the determination of strychnine and crimidine
      in biological samples.
AB  - In an attempt to improve the sensitivity and selectivity of thin-layer
      chromatographic analysis for the detection of strychnine and crimidine in
      biological samples, a rapid high-performance thin-layer chromatographic (HPTLC)
      method with densitometry is described. Fortified dog serum and stomach content
      samples were analyzed after extraction with chloroform. Quantitation was achieved
      by densitometry in the ultraviolet (UV) range (260 nm) of HPTLC silica gel 60
      plates. Detection of trace levels as low as 5 ng proved feasible. Linearity was
      obtained over a range of 10-250-ng deposits for crimidine and 12.5-250-ng
      deposits for strychnine with simple or F254 plates. No interferences were
      observed in the UV spectra (220-380 nm) when peaks obtained with HPTLC of the
      standard substances and positive biological contents were scanned.

PMID- 8735201
TI  - Simultaneous gas chromatographic determination of four toxic gases generally
      present in combustion atmospheres.
AB  - The measurement of combustion gases produced by burning aircraft cabin materials
      poses a continuing limitation for smoke toxicity research. Because toxic effects
      of gases depend on both their concentrations and the duration of exposure,
      frequent atmosphere sampling is necessary to define the gas concentration
      exposure time curve. A gas chromatographic (GC) method was developed for the
      simultaneous analyses of carbon monoxide (CO), hydrogen sulfide (H2S), sulfur
      dioxide (SO2), and hydrogen cyanide (HCN). The method used an MTI M200 dual
      column gas chromatograph equipped with 4-m molecular sieve-5A and 8-m PoraPlot-U
      wall-coated capillary columns and two low-volume, high-sensitivity thermal
      conductivity detectors. Detectability (in parts per million [ppm]) and retention
      times (in seconds) for the gases were as follows: CO, 100 ppm, 28 s; H2S, 50 ppm,
      26 s; SO2, 125 ppm, 76 s; and HCN, 60 ppm, 108 s. The method was effective for
      determining these gases in mixtures and in the combustion atmospheres generated
      by burning wool (CO, HCN, and H2S) and modacrylic fabrics (CO and HCN). Common
      atmospheric gaseous or combustion products (oxygen, carbon dioxide, nitrogen,
      water vapor, and other volatiles) did not interfere with the analyses. However,
      filtration of the combustion atmospheres was necessary to prevent restriction of
      the GC sampling inlet by smoke particulates. The speed, sensitivity, and
      selectivity of this method make it suitable for smoke toxicity research and for
      evaluating performance of passenger protective breathing equipment. Also, this
      method can potentially be modified to analyze these gases when they are liberated
      from biosamples.

PMID- 8735202
TI  - The effect of glutaraldehyde adulteration of urine specimens on syva EMIT II
      drugs-of-abuse assays.
AB  - The effect of glutaraldehyde (the active component of "UrinAid") on Syva EMIT II
      drugs-of-abuse screening assays was studied. It was found that, dependent on the
      assay involved, concentrations of between 0.75 and 2.00% (v/v) of glutaraldehyde
      in urine could give rise to false-negative screening results. A simple method for
      identifying urine specimens that have been adulterated with glutaraldehyde, based
      on final absorbance rate readings (dA/min), is proposed.

PMID- 8735204
TI  - An overdose of risperidone.
AB  - A fatality resulting from the suicidal ingestion of risperidone is described. The
      decedent had a lengthy history of mental illness but was otherwise healthy.
      Biological fluid samples obtained at autopsy were analyzed for risperidone by
      high-performance liquid chromatography. The blood concentration of risperidone
      was 1.8 mg/L, the urine concentration was 14.4 mg/L, and the concentration in the
      gastric contents was 34.6 mg/L (1.04 mg total). The 9-hydroxy-risperidone
      metabolite was not detected in the blood or gastric contents; however, the urine
      contained 17.8 mg/L of this metabolite.

PMID- 8735203
TI  - Detection of codeine and phenobarbital in sweat collected with a sweat patch.
AB  - Six male and two female subjects participated in a clinical study to determine
      the time course, the cumulative excretion, the intrasubject variability, the
      influence of site application, and the concentrations of codeine or phenobarbital
      in sweat following administration of a single dose of the drug. The doses of
      codeine and phenobarbital were 90 and 100 mg. respectively. Sweat was collected
      by means of a Sudormed sweat patch. Patches were removed at specified times over
      1 week, and the drug content was determined by gas chromatography-mass
      spectrometry using deuterated internal standards. Codeine was detectable at 1 h
      following the administration, and a plateau concentration was observed on the
      third day. The peak codeine concentration was observed during the 12-24-h period.
      Morphine was never detected in sweat. In contrast, phenobarbital was first
      observed 3 h after administration, and cumulative excretion was continual
      throughout the week. Intersubject variability was enormous, as the concentrations
      for the same dose were in a magnitude of 1-5. Concentrations were in the range of
      2-127 and 0.5-33 ng per patch for codeine and phenobarbital, respectively. The
      influence of the site of patch application was evaluated by analysis of six
      patches, all removed at the same time (24 h) in two subjects receiving 90 mg
      codeine. Codeine concentrations differed by a magnitude of 1-3 according to the
      area of application: the upper arm, the back, and the ribs. These data suggest
      that the sweat patch technology can be useful for documenting drug use over a 1
      week period of surveillance.

PMID- 8735205
TI  - Marijuana detection times: does the methodology validate the conclusions?

PMID- 8735206
TI  - Historical anecdote related to chemical tests for intoxication.

PMID- 8735207
TI  - Potential for false-positive results by the TRIAGE panel of drugs-of-abuse
      immunoassay.

PMID- 8735208
TI  - A response to "Serum-ethanol determination: comparison of lactate and lactate
      dehydrogenase interference in three enzymatic assays".

PMID- 8735209
TI  - A backward look at urinary tract infections.

PMID- 8735210
TI  - Management of nocturnal childhood enuresis in managed care: a new challenge.

PMID- 8735211
TI  - Pediatric urinary tract infections.

PMID- 8735212
TI  - Proteinuria.

PMID- 8735213
TI  - Hematuria.

PMID- 8735214
TI  - Epidemiology of pediatric kidney diseases.

PMID- 8735215
TI  - The human homologue of the weaver mouse gene in familial and sporadic Parkinson's
      disease.
AB  - The pathological hallmark of Parkinson's disease is cell death of dopaminergic
      neurons in the substantia nigra, resulting in striatal dopaminergic deficit and a
      clinical syndrome dominated by disorders of movement. The cause for this cell
      loss is unknown, but the possibility of a contributing genetic factor is
      increasingly recognized. Homozygous weaver mice, a mutant mouse strain, display
      progressive postnatal depletion of dopaminergic cells in the mesencephalon and
      have thus been proposed as an animal model for Parkinson's disease. Recently,
      mGIRK2, a putative G-protein inward rectifier K+ channel, has been identified as
      the causative gene in the weaver mouse and a homozygous mutation has been
      described in the H5 pore region of this channel. The human homologue of mGIRK2,
      KCNJ7 or hiGIRK2, has previously been isolated on chromosome 21q22.1. A possible
      involvement of this gene in the pathogenesis of Parkinson's disease has been
      discussed. To evaluate the possibility of a shared genetic defect in weaver mouse
      and Parkinson's disease, we analysed the H5 pore region of hiGIRK2 in familial
      and sporadic cases of Parkinson's disease. The sequence was normal in all cases
      examined, suggesting a differing aetiology of nigral cell loss in Parkinson's
      disease and weaver mice.

PMID- 8735216
TI  - Stimulation of lumbar sympathetic nerves may produce hindlimb vasodilation via
      the release of pre-formed stores of nitrosyl factors.
AB  - The physiological activation of lumbar sympathetic nerves by air-jet stress
      produces a hindlimb vasodilation in conscious rats. Although the nitric oxide
      synthase inhibitor N(G)-nitro-L-arginine methyl ester markedly reduces the
      duration of this air-jet stress-induced vasodilation, it does not prevent the
      initial fall in resistance. These data suggest that the vasodilation is initiated
      by the release of an as yet unidentified factor, whereas the vasodilation is
      sustained by the release of nitric oxide or newly synthesized nitrosyl factors
      such as S-nitrosothiols. At present, the possibility that neurogenic vasodilation
      may be initiated by the release of pre-formed pools of nitrosyl factors from
      storage sites within the hindlimb vasculature has not been addressed. We reasoned
      that if nitrosyl factors do exist in storage pools, then we should be able to
      demonstrate a "use-dependent" loss of vasodilation after nitric oxide synthesis
      inhibition which would be the result of a gradual depletion of the releasable
      pools of these nitrosyl factors. In the present study, we examined the effects of
      repeated episodes of direct electrical stimulation of the lumbar sympathetic
      chain on ipsilateral hindlimb vascular resistance in pentobarbital-anesthetized
      rats prior to and following administration of the nitric oxide synthesis
      inhibitors N(G)-nitro-L-arginine methyl ester (10, 25 or 100 mumol/kg i.v.) or
      N(G)-nitro-L-arginine (50 mumol/kg i.v.). Three episodes of electrical
      stimulation of 3.2 +/- 0.4 V (20 Hz, 5 ms duration, 5 ms delay for 10 s given 5
      min apart) produced pronounced and reproducible reductions in hindlimb vascular
      resistance in the ipsilateral hindlimb (-56 +/- 5%, -55 +/- 5% and -53 +/- 6%,
      respectively), but no changes in mean arterial pressure. Three episodes of
      electrical stimulation at 4.8 +/- 0.4 V also caused reproducible decreases in
      hindlimb resistance (-59 +/- 7%, -61 +/- 9% and -64 +/- 12%) and minor but
      reproducible decreases in blood pressure. The vasodilation produced by the first
      electrical stimulation at 3.2 +/- 0.4 V was completely abolished by a 25 mumol/kg
      dose of N(G)-nitro-L-arginine methyl ester (-11 +/- 9%). The initial episode of
      electrical stimulation at 4.8 +/- 0.4 V produced a pronounced fall in ipsilateral
      hindlimb resistance in the N(G)-nitro-L-arginine methyl ester-treated animals
      whereas the second and third stimulations produced progressively smaller
      vasodilations (-55 +/- 4%, -34 +/- 3% and -19 +/- 2%, respectively). The 10
      mumol/kg dose of N(G)-nitro-L-arginine methyl ester was not effective whereas the
      100 mumol/kg dose produced similar effects as the 25 mumol/kg dose. The 50
      mumol/kg dose of N(G)-nitro-L-arginine produced similar effects as the higher
      doses of N(G)-nitro-L-arginine methyl ester. Those results suggest that lower
      intensity electrical stimulation of the lumbar sympathetic nerves produces
      vasodilation via the release of nitric oxide or newly synthesized nitrosyl
      factors such as S-nitrosothiols. In contrast, the vasodilation produced by higher
      intensity electrical stimulation may involve the mobilization and release of pre
      formed pools of nitrosyl factors which undergo a "use-dependent" depletion in the
      absence of nitric oxide synthesis. These pre-formed pools of nitrosyl factors may
      exist within the sympathetic nerves themselves. In addition, they may be stored
      within the vascular endothelium and released by neurogenically-derived
      neurotransmitters/neuromodulators.

PMID- 8735217
TI  - Differential induction and intracellular localization of SCG10 messenger RNA is
      associated with neuronal differentiation.
AB  - The differentiation of neurons involves the establishment of distinct molecular
      compartments which regulate neuronal shape and function. This requires targeting
      of specific gene products to growth-associated regions of the neuron. We have
      investigated the temporal and spatial regulation of SCG10 gene expression during
      neuronal differentiation. There are two SCG10 messenger RNAs, 1 and 2 kg in
      length, which encode the same growth-associated protein. These messenger RNAs
      were found to be differentially regulated during the onset of neurite outgrowth
      in early rat cerebellum development. In PC12 cells, the two SCG10 messenger RNAs
      were shown to be differentially induced by nerve growth factor. Regulation of the
      2 kb messenger RNA, but not the 1 kb messenger RNA, is dependent on the
      differentiation of PC12 cells, indicating that post-transcriptional regulation of
      SCG10 expression during neurite outgrowth. Spatial regulation of the 2 kb SCG10
      messenger RNA distribution during brain development was examined by in situ
      hybridization. The 2 kb messenger RNA was found to be localized to the neuronal
      pole where outgrowth was occurring, within differentiating neurons in vivo.
      Intracellular localization of SCG10 messenger RNA was also observed in
      differentiating primary cultured neurons, with the 2 kb messenger RNA transported
      into growing neurites during the development of neuronal polarity. In neurons
      which had developed polarity, the 2 kb SCG10 messenger RNA was consistently found
      in the cell body and axon. This study demonstrates both temporal and spatial post
      transcriptional regulation of SCG10 expression which is associated with neurite
      outgrowth. The directed transport and positional translation of SCG10 messenger
      RNA provide a potential mechanism for protein targeting and the creation of
      molecular compartments during neuronal differentiation.

PMID- 8735218
TI  - Optic nerve glia secrete a low-molecular-weight factor that stimulates retinal
      ganglion cells to regenerate axons in goldfish.
AB  - The ability of lower vertebrates to regenerate an injured optic nerve has been
      widely studied as a model for understanding neural development and plasticity. We
      have recently shown that, in goldfish, the optic nerve contains two molecules
      that stimulate retinal ganglion cells to regenerate their axons in culture: a low
      molecular-weight factor that is active even at low concentrations (axogenesis
      factor-1) and a somewhat less active polypeptide of molecular weight 10,000
      15,000 (axogenesis factor-2). Both are distinct from other molecules described
      previously in this system. The present study pursues the biological source and
      functional significance of axogenesis factor-1. Earlier studies have shown that
      cultured goldfish glia provide a highly favorable environment for fish or rat
      retinal ganglion cells to extend axons. We report that the glia in these cultures
      secrete high levels of a factor that is identical to axogenesis factor-1 in its
      chromatographic properties and biological activity, along with a larger molecule
      that may coincide with axogenesis factor-2. Axogenesis factor-1 derived from
      either goldfish glial cultures or optic nerve fragments is a hydrophilic molecule
      with an estimated molecular weight of 700-800. Prior studies have reported that
      goldfish retinal fragments, when explanted in organ culture, only extend axons if
      the ganglion cells had been "primed" to begin regenerating in vivo for one to two
      weeks. However, axogenesis factor-1 caused the same degree of outgrowth
      irrespective of whether ganglion cells had been induced to regenerate new axons
      in vivo. Moreover, ganglion cells primed to begin regenerating in vivo continued
      to extend axons in culture only when axogenesis factor-1 was present. In summary,
      this study shows that glial cells of the goldfish optic nerve secrete a low
      molecular-weight factor that initiates axonal regeneration from retinal ganglion
      cells.

PMID- 8735219
TI  - Neurotrophin-4/5 selectively protects nigral calbindin-containing neurons in rats
      with medial forebrain bundle transections.
AB  - Three neurotrophic factors associated with the nigrostriatal dopaminergic system
      were tested for their trophic potential to rescue degenerating substantia nigra
      dopaminergic neurons in adult rats with transections of the medial forebrain
      bundle. Axotomy of nigral dopaminergic neurons results in a retrograde
      degeneration of their cell bodies. Unilateral transections resulted in a partial
      reduction of the number of dopaminergic neurons as identified by
      immunocytochemistry for tyrosine hydroxylase to approximately half of the number
      of neurons present on the intact contralateral substantia nigra. A similar
      percentage loss was found for the subpopulation of nigral neurons which contain
      the calcium binding protein calretinin. In contrast, the small subpopulation of
      neurons which contain calbindin was less sensitive to the lesion and showed only
      mild loss in the number of cells, which was reduced to 87% of control.
      Neurotrophin-4/5, transforming growth factor alpha or basic fibroblast growth
      factor were infused supranigrally for two weeks after transection. None of the
      trophic factors tested reversed the loss of tyrosine hydroxylase-positive or
      calretinin-positive cells. In contrast, neurotrophin-4/5, but not transforming
      growth factor alpha or basic fibroblast growth factor, was found to reverse the
      axotomy-induced loss of calbindin-positive neurons and indeed increased the
      number of cells to 45% above control levels. In addition, neurotrophin-4/5
      elevated the number of calbindin-containing neurons in intact unlesioned animals
      to 15% above control. These findings suggest that neurotrophin-4/5 selectively
      acts on nigral calbindin neurons following medial forebrain bundle transection
      and prevents these cells from degenerating.

PMID- 8735220
TI  - Short increase of BDNF messenger RNA triggers kainic acid-induced neuronal
      hypertrophy in adult mice.
AB  - Neurotrophin gene expression in adult brain varies according to physiological
      activity and following brain injury, suggesting a role in neuronal maintenance
      and plasticity. However, the exact roles and mechanisms of action of
      neurotrophins in the adult brain are still poorly understood. We have recently
      demonstrated that neurons of the adult mouse dentate gyrus can develop a
      conspicuous morphogenetic response to intrahippocampal injection of kainic acid.
      This response is correlated with long-lasting overexpression of the brain-derived
      neurotrophic factor gene, suggesting a causal relationship between molecular and
      structural changes. To test this hypothesis, brain-derived neurotrophic factor
      messenger RNA were sequestered in vivo by administration of antisense
      oligodeoxynucleotides. When administered before 20 h post-kainate, antisense
      oligodeoxynucleotides totally prevented the kainate-induced neuronal hypertrophy,
      while sense or missense sequences had no effect. On the other hand, the
      hypertrophic response was observed when antisense administration was begun 24 h
      post-kainate, indicating an involvement of brain-derived neurotrophic factor
      messenger RNA in the initiation of structural changes, but not in their
      evolution. The hypertrophy was blocked by inhibition of tyrosine kinase
      activities by K252a, suggesting an involvement of Trk high affinity receptors.
      Administration of human recombinant brain-derived neurotrophic factor without
      previous treatment by kainate failed to induce any morphogenetic response. These
      results show that a short activation of the brain-derived neurotrophic factor
      gene can, in association with neuronal activation by kainate, trigger dramatic
      and long-lasting morphological changes in adult neurons. A physiological role of
      brain-derived neurotrophic factor in adult brain could therefore be to link, by
      autocrine/paracrine action, activation of glutamate receptors and neuronal
      morphological adaptive responses.

PMID- 8735221
TI  - Maintenance of sympathetic innervation into the hippocampal formation requires a
      continuous local availability of nerve growth factor.
AB  - The sprouting of peripheral sympathetic fibers into the septally denervated
      hippocampal formation is a well-characterized model of lesion-induced plasticity.
      While various studies have demonstrated the importance of nerve growth factor for
      evoking sympathetic sprouting, little is known concerning whether nerve growth
      factor continues to be required for maintaining innervation once it has occurred.
      In the present study we have addressed this point by (i) investigating the
      consequences of withdrawing exogenous nerve growth factor support from rats in
      which sympathetic innervation was enhanced by a nerve growth factor infusion and
      (ii) using blocking antibodies to interfere with the actions of endogenous nerve
      growth factor. The results of this investigation clearly indicate that a
      continuous supply of nerve growth factor (either exogenous or endogenous) is
      required to maintain sympathetic innervation within the hippocampal formation.
      Evidence is also provided demonstrating that the nerve growth factor must be made
      available locally within a given region to evoke and maintain the sympathetic
      innervation within this location. Axonal rearrangement within the developing and
      adult brain is believed to be an important mechanism underlying learning and
      memory is crucial for lesion-related plasticity. In various experimental
      paradigms, nerve growth factor has been shown to be an important cue for
      initiating axonal remodeling. In the current study, we have demonstrated that
      once such rearrangements have taken place, nerve growth factor may also be
      required to maintain them.

PMID- 8735222
TI  - Cyclin D1 messenger RNA is induced in microglia rather than neurons following
      transient forebrain ischaemia.
AB  - Following 30 min of forebrain ischaemia in the rat, delayed neuronal death occurs
      in the CA1 sector of the hippocampus within two to three days, whereas neurons in
      other selectively vulnerable regions, such as the dorsolateral striatum, die
      within 6-12 h. In this study, we investigated cyclin D1 expression, which codes
      for a regulatory protein in cell cycle regulation, but it is also induced in
      sympathetic neurons undergoing programmed cell death. Cyclin D1 messenger RNA
      could not be detected by in situ hybridization techniques in brains of control
      rats, but was found at one and two days after ischaemia in regions of the
      dorsolateral striatum with neuronal degeneration. DNA fragmentation in this
      region, identified by the terminal transferase biotinylated-UTP nick end
      labelling (TUNEL) procedure, was observed from 6 h after ischaemia onward. In the
      hippocampus, increased levels of cyclin D1 messenger RNA were found at two and
      three days after ischaemia in the striatum pyramidale of the CA1 sector. This
      expression was associated with the occurrence of neuronal damage and TUNEL
      stained neurons. By seven days cyclin D1 messenger RNA was found in hardly any
      brain structure. There was no temporospatial overlap of cyclin D1 expression with
      the expression of the immediate-early genes c-fos, c-jun, and mkp-1, a result
      which is clearly distinct from findings in sympathetic ganglion neurons
      undergoing programmed cell death. These results do not suggest a role for cyclin
      D1 in neuronal cell death following transient forebrain ischaemia. The similarity
      of the cyclin D1 expression profile with that of the microglia-specific CR3
      complement receptor beta-subunit messenger RNA, and the results of combined in
      situ hybridization and microglia-specific immunohistochemistry suggest that
      microglia are the source of cyclin D1 messenger RNA in the postischaemic brain.
      Since cyclin D1 codes for a critical regulatory protein for progression of the G0
      to G1 phase in the cell cycle and we did not observe prominent occurrence of DNA
      fragmentation in microglial cells in the hippocampus at time points when cyclin
      D1 messenger RNA was found, we suggest that cyclin D1 induction is involved in
      the onset of microglial cell proliferation.

PMID- 8735223
TI  - Contrasting effects of fetal CA1 and CA3 hippocampal grafts on deficits in
      spatial learning and working memory induced by global cerebral ischaemia in rats.
AB  - Functional effects of fetal hippocampal field grafts were assessed in rats with
      spatial learning and memory impairments following global cerebral ischaemia.
      Experiment 1 examined effects of grafts dissected from fields CA1 and CA3 at
      embryonic day 19 and from the dentate gyrus at postnatal day 1. Cell suspensions
      (15,000 cells/site) were implanted bilaterally at two points above the dorsal CA1
      area two weeks after four-vessel occlusion (electrocoagulation of the vertebral
      arteries followed the 24 h later by occlusion of the carotid arteries for 15
      min). Histological examination showed that CA1 neuronal loss (60-70%) was
      equivalent in all ischaemic groups and that 80% of CA1 and 60% of CA3 grafts
      survived and were sited appropriately in the alveus or corpus callosum above the
      area of ischaemic CA1 damage in the host, but there was no survival of dentate
      grafts. Results from rats with poor pyramidal cell graft survival were excluded,
      but those from rats with non-surviving dentate grafts were retained as an
      additional control group. Acquisition in the water maze was examined nine and 25
      weeks after transplantation, and spatial working memory was assessed in three
      door runway and water maze matching-to-position tasks 19 and 28 weeks after
      grafting, respectively. For water maze acquisition rats were trained with two
      trails/day and a 10 min inter-trial interval for 10-12 days to locate a submerged
      platform. Ischaemic rats with CA1 grafts learned the platform position as rapidly
      as non-ischaemic controls, searched appropriately in the training quadrant and
      were accurate in heading towards the platform, but were initially impaired on
      recall of the precise platform position on probe trials with the platform
      removed. Performance of ischaemic controls and groups with CA3 and non-surviving
      dentate graft groups was significantly impaired relative to controls and to the
      CA1 grafted group. The CA1 grafted group was also as successful as controls in
      matching-to-position in the water maze and substantially superior to the other
      ischaemic groups, assessed using three trials/day, with a 30-s inter-trial
      interval and a different platform position on each day. In a more complex
      matching-to-position task in the three-door runway, the performance of the CA1
      grafted group was significantly impaired relative to controls, although superior
      to that of the other ischaemic control and graft groups. Functional recovery with
      CA1, but not CA3, grafts in ischaemic rats was replicated in a second experiment
      which assessed water maze acquisition and working memory at 10 and 14 weeks after
      transplantation, in rats with 90% graft survival. These results indicate that
      long-lasting, task-dependent improvements can be seen in ischaemic rats with CA1
      fetal grafts in both aversively and appetitively motivated spatial learning
      tasks. The findings suggest that functional recovery requires homotypic
      replacement of CA1 cells damaged by ischaemia, rather than provision of
      structurally similar glutamate-releasing CA3 pyramidal cells.

PMID- 8735224
TI  - Activation of serotonergic and noradrenergic neurotransmission in the rat
      hippocampus after peripheral administration of bacterial endotoxin: involvement
      of the cyclo-oxygenase pathway.
AB  - An endotoxic challenge produces pronounced effects on the immune, endocrine and
      central nervous systems. However, information on the brain structures and
      neurotransmitter systems participating in the physiological responses after
      stimulation of the immune system is still scarce. Using an in vivo microdialysis
      method is conscious, freely moving rats, the present study describes the effects
      of an endotoxic challenge on hippocampal serotonergic and noradrenergic
      neurotransmission. Rats were equipped with a microdialysis probe in the
      hippocampus, which enables the stress-free measurement of extracellular
      concentrations of serotonin, noradrenaline and their respective metabolites 5
      hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenylglycol. The behavioral
      activity was scored by measurement of the time during which rats were active
      (locomotion, grooming, eating, drinking). In the control rats a significant,
      positive relationship between the behavioral activity and hippocampal
      extracellular levels of serotonin, noradrenaline and 3-methoxy-4
      hydroxyphenylglycol was found. Intraperitoneally injected bacterial endotoxin
      (lipopolysaccharide; 100 micrograms/kg body weight) increased extracellular
      concentrations of serotonin, 5-hydroxyindoleacetic acid, noradrenaline and 3
      methoxy-4-hydroxyphenylglycol, whereas the behavioral activity was largely
      reduced, thus disrupting the correlation between behavioral activity and
      hippocampal levels of serotonin, noradrenaline and 3-methoxy-4
      hydroxyphenylglycol. Intraperitoneal pretreatment of rats with the cyclo
      oxygenase inhibitor indomethacin attenuated, but did not completely abolish, the
      endotoxin-induced increases in hippocampal extracellular levels of serotonin,
      noradrenaline and their metabolites. From these results it may be concluded that
      the hippocampal serotonin and noradrenaline neurotransmitter systems are part of
      the brain circuitry responsive to an endotoxic challenge. Moreover, arachidonic
      acid metabolites seem to represent important, but not the sole, mediators of the
      endotoxin-induced changes in hippocampal neurotransmission.

PMID- 8735225
TI  - Physiological and pharmacological profile of trans-azetidine-2,4-dicarboxylic
      acid: metabotropic glutamate receptor agonism and effects on long-term
      potentiation.
AB  - In this study, we biochemically analysed the effects of the novel metabotropic
      glutamate receptor agonist trans-azetidine-2,4-dicarboxylic acid and examined its
      role in hippocampal long-term potentiation. In cell lines expressing metabotropic
      receptor 1 or 5 subtypes, the compound stimulated phosphoinositide hydrolysis
      with EC50 values of 189.4 +/- 6.4 and 32.2 +/- 8.3 microM, respectively. In
      hippocampal slices, trans-azetidine-2,4-dicarboxylic acid also increased
      phosphoinositide hydrolysis, yet failed to show any effect on forskolin
      stimulated formation of cyclic AMP, even if 1 mM azetidine was applied. Since
      trans-azetidine-2,4-dicarboxylic acid (20 mM in 5 microliters) injected
      cerebroventricularly prolongs long-term potentiation induced by weak
      tetanization, a possible interaction with N-methyl-D-aspartate receptors was
      investigated using patch-clamp techniques. Neither facilitation of N-methyl-D
      aspartate (500 microM) currents nor induction of non-specific currents was
      observed in the presence of 50 and 500 microM azetidine. Strong tetanus-induced
      long-term potentiation in the dentate gyrus of freely moving rats was not
      influenced by azetidine. In combination with the antagonist (R,S)-alpha-methyl-4
      carboxyphenylglycine (200 mM in 5 microliters), however, the potentiation was
      attenuated and returned to baseline within 90 min. Blockade of N-methyl-D
      aspartate receptors using 2-amino-5-phosphonopentanoate (20 mM in 5 microliters)
      prevented the potentiation in controls, but not in the azetidine group, where
      normal potentiation was observed for both the population spike amplitude and the
      excitatory postsynaptic potential. These data suggest that (i) trans-azetidine
      2,4- dicarboxylic acid is an agonist at glutamate metabotropic receptors; (ii) a
      facilitation of induction and maintenance of long-term potentiation via N-methyl
      D-aspartate receptors seems unlikely; and (iii) pharmacological activation of
      metabotropic receptors prior to tetanization appears to bypass the N-methyl-D
      aspartate receptor dependence of the potentiation. In conclusion, a role for
      metabotropic glutamate receptors in both short-term and long-term potentiation is
      indicated by these data.

PMID- 8735226
TI  - Modifications in glutamatergic transmission after dopamine depletion of the
      nucleus accumbens. A combined in vivo/in vitro electrophysiological study in the
      rat.
AB  - The interaction between the glutamatergic and dopaminergic input in the nucleus
      accumbens was examined by studying the effects of dopamine depletion of the
      nucleus accumbens on the local field potentials, and the L-glutamate elicited
      responses of the nucleus accumbens in anaesthetized rats in vivo. A
      characteristic field potential in the nucleus accumbens is evoked by electrical
      stimulation of the fornix/fimbria fibres, with a monosynaptic positive peak at 10
      ms (P10). Rats were unilaterally injected with 6-hydroxydopamine in the nucleus
      accumbens. The contralateral accumbens was sham lesioned. The rats were divided
      into short-term and long-term survival groups of one to two weeks and 24 weeks,
      respectively. In the short-term group, a striking increase (up to three times) of
      the amplitude of the P10 components, at the site of the lesion, compared with the
      sham lesioned contralateral accumbens and untreated rats, was found. The long
      term group could still display a slight increase although on average this was not
      significantly different from controls. In the short-term group, at the centre of
      the lesion, the paired-pulse facilitation ratio was significantly smaller than at
      the more ventral, less denervated, border of the accumbens. These differences
      were no longer visible in the long-term group. Single-unit activity of the
      accumbens, elicited by the iontophoretical application of L-glutamate showed, in
      controls, a maximal firing frequency ranging from 5 to 40 Hz (mean 25 Hz),
      whereas in the short-term group more than 50% of the accumbens neurons fired with
      higher frequencies, reaching up to 90 Hz (mean 55 Hz). In the long-term group the
      firing frequency varied from 5 to 60 Hz (mean 41 Hz). No changes in threshold
      ejection glutamate current were found for both lesioned groups. In control rats
      the L-glutamate elicited responses of six cells tested could be suppressed by
      dopamine whereas in lesioned rats three of the six cells tested were unresponsive
      to dopamine. Intracellular recordings of accumbens cells in slices in 6
      hydroxydopamine and sham lesioned rats, showed no significant changes in the
      intrinsic membrane properties, e.g. resting membrane potential, input resistance,
      spike threshold, action potential amplitude or duration. We conclude that
      dopamine denervation leads to an increase of excitability of the principal
      accumbens neurons. This is reflected by the increase of the firing frequency of
      these cells and of the amplitude of the evoked field potentials. The former is
      more likely of postsynaptic origin whereas the latter may also have a presynaptic
      contribution. These effects cannot be attributed to changes in intrinsic membrane
      properties of the cells.

PMID- 8735227
TI  - Reduction in enkephalin and substance P messenger RNA in the striatum of early
      grade Huntington's disease: a detailed cellular in situ hybridization study.
AB  - The expression of enkephalin and substance P messenger RNAs was examined in the
      caudate-putamen of human post mortem tissue from control and Huntington's disease
      tissue using in situ hybridization techniques and human specific enkephalin and
      substance P [35S] oligonucleotides. Macroscopic and microscopic quantification of
      enkephalin and substance P gene expression was carried out using computer
      assisted image analysis. Tissue was collected from six control cases with no sign
      of neurological disease and six Huntington's disease cases ranging from grades 0
      to 3 as determined by neuropathological evaluation. The clinical and pathological
      diagnosis of Huntington's disease was confirmed unequivocally by genetic analysis
      of the CAG repeat length in both copies of IT15, the Huntington's disease gene. A
      marked reduction in both enkephalin and substance P messenger RNAs was detected
      in all regions of the caudate nucleus and putamen in Huntington's disease grades
      2/3 when compared to controls; in the dorsal caudate few enkephalin or substance
      P messenger RNA-positive cells were detected. For the early grade (0/1)
      Huntington's disease cases, a heterogeneous reduction in both enkephalin and
      substance P messenger RNAs were noted; for enkephalin messenger RNA the striatal
      autoradiograms displayed a conspicuous patchy appearance. Detailed cellular
      analysis of the dorsal caudate revealed a striking reduction in the number of
      enkephalin and substance P messenger RNA-positive cells detected and in the
      intensity of hybridization signal/cell. These data suggest that both the
      "indirect" GABA/enkephalin and "direct" GABA/substance P pathways are perturbed
      very early in the course of the disease and that these early changes in chemical
      signalling may possibly underlie the onset of clinical symptoms.

PMID- 8735228
TI  - Decreased neuronal nitric oxide synthase messenger RNA and somatostatin messenger
      RNA in the striatum of Huntington's disease.
AB  - The cellular abundance of neuronal nitric oxide synthase and somatostatin
      messenger RNAs was compared in the caudate nucleus, putamen and sensorimotor
      cortex of Huntington's disease and control cases. Neuronal nitric oxide synthase
      messenger RNA was significantly decreased in the caudate nucleus and putamen, but
      not in the sensorimotor cortex in Huntington's disease; the decrease in neuronal
      nitric oxide synthase messenger RNA became more pronounced with the severity of
      the disease. Somatostatin gene expression was significantly decreased in the
      dorsal putamen in Huntington's disease, but was essentially unchanged in all
      other regions examined. The density of neurons expressing detectable levels of
      neuronal nitric oxide synthase messenger RNA was reduced in the striata of
      Huntington's disease cases with advanced pathology; the density of neurons
      expressing detectable levels of somatostatin messenger RNA was similar in control
      and Huntington's disease cases. Neuropeptide Y-, somatostatin- and NADPH
      diaphorase-positive neurons were consistently present throughout the striatum
      across all the grades of the disease. Neuronal nitric oxide synthase and NADPH
      diaphorase activity (a histochemical marker for nitric oxide synthase-containing
      neurons) co-localize with somatostatin and neuropeptide Y in interneurons in the
      human striatum and cerebral cortex. Although the neurodegeneration associated
      with Huntington's disease is most evident in the striatum (particularly the
      dorsal regions), neuronal nitric oxide synthase/neuropeptide Y/somatostatin
      interneurons are relatively spared. Nitric oxide released by neuronal nitric
      oxide synthase-containing neurons may mediate glutamate-induced excitotoxic cell
      death, a mechanism proposed to be instrumental in causing the neurodegeneration
      seen in Huntington's disease. The results described here suggest that although
      the population of interneurons containing somatostatin, neuropeptide Y and
      neuronal nitric oxide synthase do survive in the striatum in Huntington's disease
      they are damaged during the course of the disease. The results also show that the
      reduction in neuronal nitric oxide synthase and somatostatin messenger RNAs is
      most pronounced in the more severely affected dorsal regions of the striatum.
      Furthermore, the loss of neuronal nitric oxide messenger RNA becomes more
      pronounced with the severity of the disease; thus implying a down-regulation in
      neuronal nitric oxide synthase messenger RNA synthesis, and potentially neuronal
      nitric oxide synthase protein levels, in Huntington's disease.

PMID- 8735229
TI  - c-Fos immunoreactivity in the sexually dimorphic area of the hypothalamus and
      related brain regions of male gerbils after exposure to sex-related stimuli or
      performance of specific sexual behaviors.
AB  - The sexually dimorphic area of the gerbil hypothalamus is essential for male sex
      behavior. To determine which aspects of mating activate its cells, or cells near
      or connected to it, we visualized c-Fos in the brains of male gerbils that had
      been exposed to various types of sex-related stimuli or that had displayed
      various aspects of sex behavior. Five groups of males were placed in familiar
      arenas containing sex-related odors. All subjects had previously mated in these
      arenas. For four groups, a female was introduced and remained with the male until
      he ejaculated, intromitted, mounted or sniffed her. Males in the fifth group
      remained in the arena alone. Males in a sixth group were placed in a clean arena
      in another room. These males were also familiar with this arena but had never
      encountered a female there. The seventh group remained in their home cages. The
      posterodorsal preoptic nucleus, the lateral part of the posterodorsal medial
      amygdala, the medial part of the sexually dimorphic area and the parvicellular
      part of the subparafascicular nucleus of the thalamus expressed c-Fos after
      ejaculation. Whether these cells triggered ejaculation or responded to it is not
      clear. The latter two areas also expressed c-Fos whenever males were exposed to
      the sex arena, but the sexually dimorphic area pars compacta did not express c
      Fos under any condition. The medial core of the nucleus accumbens, the
      ventrolateral septum, the caudomedial bed nucleus of the stria terminalis, the
      medial/central part of the posterodorsal medial amygdala and the lateral part of
      the sexually dimorphic area also expressed c-Fos when males entered the sex
      arena. The ventrolateral part of the ventromedial nucleus of the hypothalamus
      expressed c-Fos whenever males were with females. None of the 31 areas studied
      responded to mounting or intromission, but the zona incerta, the
      amygdalohippocampal area, the lateral part of the sexually dimorphic area and the
      area lateral to the medial part of the sexually dimorphic area showed progressive
      increases in c-Fos expression as mating progressed. The area dorsal to the medial
      part of the sexually dimorphic area, the paraventricular nucleus of the
      hypothalamus, the ventral premammillary nucleus and the retrorubral field showed
      the same level of c-Fos expression when males were exposed to the non-sexual
      context as when they were exposed to the sexual one. While a projection to the
      retrorubral field from the sexually dimorphic area is critical for male sex
      behavior, the retrorubral field did not show a sex-related c-Fos response. The
      data suggest that brain regions involved in male sex behavior are involved in
      different aspects of it and that this can also apply to different subsets of
      cells in each area. The data also indicate that cells involved in mating do not
      necessarily show mating-related patterns of c-Fos expression. Thus, while c-Fos
      is useful for identifying areas involved in mating, or other behaviors, its
      characteristics could cause relevant areas to be overlooked.

PMID- 8735230
TI  - The action of oxytocin originating in the hypothalamic paraventricular nucleus on
      mitral and granule cells in the rat main olfactory bulb.
AB  - The effects of electrical stimulation of the hypothalamus paraventricular nucleus
      on the spontaneous firing of mitral and granule cells in the main olfactory bulb
      were examined in ovariectomized female rats under urethane anaesthesia. High
      frequency stimulation (0.5-1.0 mA, 10-20 pulses at 100 Hz) of the paraventricular
      nucleus produced inhibitory responses in 80% of mitral cells tested and
      excitatory responses in 74% of granule cells tested, with latencies ranging from
      2 to 150 s. Both responses were blocked by infusions into the olfactory bulb of
      [d(CH2)5, Tyr(Me)2]ornithine-vasotocin (10 pmol), an oxytocin antagonist, and
      mimicked by intracerebroventricular infusions (0.2 or 0.4 nmol) or
      microiontophoretic applications of oxytocin but not by intracerebroventricular
      infusions of vasopressin (1 or 2 nmol). Infusions of 0.5% lignocaine, a local
      anaesthetic, into either the medial olfactory tract or the medial forebrain
      bundle failed to block the responses of mitral and granule cells to the
      stimulation. Unilateral transections at various levels between the bulb and the
      paraventricular nucleus also failed to block the responses. There were cases in
      which significant responses of mitral and granule cells to the stimulation
      required 60 or more pulses after the lignocaine infusions or transections,
      however. These results suggest that oxytocin originating in the hypothalamic
      paraventricular nucleus reaches the olfactory bulb following its release partly
      into the cerebrospinal fluid and acts to decrease olfactory processing.

PMID- 8735231
TI  - The olfactory bulb: a critical site of action for oxytocin in the induction of
      maternal behaviour in the rat.
AB  - Expanding on research showing that oxytocin originating in the hypothalamic
      paraventricular nucleus acts to decrease olfactory processing at the level of the
      olfactory bulb, we explored the importance of oxytocin acting on the olfactory
      bulb for the onset of maternal behaviour in Wistar rats. Experiment I was
      designed to test whether spontaneous maternal behaviour following natural
      delivery is blocked by bilateral infusions of a low dose (5 fmol) of the oxytocin
      antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]ornithine-vasotocin into the
      olfactory bulb immediately after the delivery of the first pup and again just
      before a test for maternal behaviour. Intrabulbar infusions of the antagonist
      markedly delayed the occurrence of all components (retrieval, licking, nest
      building, crouching) of maternal behaviour, whereas intracerebroventricular
      infusions of the antagonist were without effect on any component as compared with
      intrabulbar infusions of saline. Experiment 2 was undertaken to determine whether
      infusions of oxytocin into the bulb induce a rapid onset of maternal behaviour in
      virgin rats. Forty-eight hours before pup presentation virgins were
      ovariectomized and treated with oestradiol benzoate. Immediately before pup
      presentation a low dose (20 pmol) of oxytocin or saline was infused bilaterally
      into the bulb or lateral ventricle. Intrabulbar infusions of oxytocin induced
      full maternal behaviour in half of the animals tested within 2 h of pup exposure,
      in contrast to the ineffectiveness of intracerebroventricular infusions of
      oxytocin and intrabulbar infusions of saline. These results suggest that the
      olfactory bulb is a critical site where oxytocin acts to induce a rapid onset of
      maternal behaviour.

PMID- 8735232
TI  - The stomatogastric nervous system: a formal approach.
AB  - A discrete mathematical formalism (d-space) which is specifically designed to
      investigate discrete aspects of behavior is applied to the foregut of decapod
      crustacea. This approach differs from continuous modeling techniques in that the
      analysis determines a structure in which the observed behavior of the foregut is
      constrained. A notation for the implementation of the formalism is developed as
      well as a coordinate system natural to the functioning of the gastric mill. The
      formalism is used to organize previous observations that suggest potential
      courses of further experimental investigation. A detailed analysis of observed
      chewing modes of the gastric mill is presented, along with a discussion of the
      overall organization of the interrelationships between these modes. The
      investigation also addresses the relationship between behavioral modes of a
      pyloric muscle found in the shrimp Palaemon. Two alternative hypotheses are
      presented to describe the relationship of the behavioral components of the
      gastric mill: an interlaced control scheme in which the components are freely
      exchanged, and a top-down control system where the chewing modes are rigidly
      separated into packages. Flow through regions of state space in time is found to
      be important in determining the relations between the discrete behavioral
      components. The behavior of the foregut, like that of other motor control
      systems, is shown to fit naturally into the d-space formalism.

PMID- 8735233
TI  - The effect of hyperosmotic treatment on the functioning of ampullary
      electroreceptor organs.
AB  - The condition of the microvilli of the apical membrane in ampullary
      electroreceptor organs of the freshwater catfish, Ictalurus nebulosus, was
      manipulated by administration of hyperosmotic solutions (500 mM) in order to
      investigate to what extent the apical surface area determines the sensitivity and
      the shape of the frequency curves. Electrophysiological recordings demonstrated
      that hyperosmotic sucrose and glucose solutions reduce the sensitivity by 80%,
      and alter the shape of the frequency curves. The synaptic delay and the average
      spontaneous activity remained almost unchanged. Calculations with an equivalent
      electric circuit of an electroreceptor cell indicate that a reduction in apical
      surface area can account for these effects. Apparently, the sensitivity and the
      frequency curves in ampullary organs in freshwater catfish depend on the apical
      surface area. A hyperosmotic urea solution proved to be less suitable to
      investigate the effect of manipulations of the apical surface area. The almost
      total loss in sensitivity caused by administration of urea is caused by both
      shunting of the stimulus by leaky tight junctions and a reduced synaptic
      efficacy. The repetitive activity observed after exposure to glucose or sucrose
      must be attributed to malfunctioning of postsynaptic parts of the receptor organ.

PMID- 8735234
TI  - Cholinergic innervation of cerebral cortex in organotypic slice cultures:
      sustained basal forebrain and transient striatal cholinergic projections.
AB  - Slices of entire forebrain hemispheres were taken from early postnatal rat pups
      and maintained as organotypic slice cultures. Basal forebrain cholinergic
      neurons, identified by histochemical staining for acetylcholinesterase, develop
      axons that grow rapidly into cerebral cortex. Ingrowth occurs by two routes: some
      axons course laterally from the basal forebrain region to reach lateral
      neocortex; others course dorsally from the septum to reach medial cortex. By one
      to two weeks in vitro, acetylcholinesterase-positive axons have extended
      throughout most of the cortical territory. In addition to basal forebrain
      cholinergic axons, the normally local circuit cholinergic neurons of the striatum
      also send axons into cerebral cortex. These striatum-derived axons can be
      distinguished from basal forebrain axons by their distinct morphological
      characteristics and by their different response to excision of the striatum or
      basal forebrain. Further, acetylcholinesterase-positive axons in cortex that
      originate from striatum appear to retract or degenerate after about one week in
      culture, while those from basal forebrain remain present and apparently healthy
      beyond two weeks. These data document the basal forebrain cholinergic ingrowth
      into cerebral cortex using this whole hemisphere slice culture system and also
      demonstrate different degrees of maintenance of cortical afferents that are
      derived from different subcortical sources.

PMID- 8735235
TI  - Vasodilatation and enhanced oxidative metabolism of the cerebral cortex provoked
      by the periaqueductal gray matter in anaesthetized rats.
AB  - The aim of the present study was to evaluate the possible contribution of the
      cerebral cortical oxidative metabolism to the cortical vasodilator action of the
      periaqueductal gray. In 70 rats with cervical cordotomy, we found that unilateral
      stimulation of the caudal third of the lateral longitudinal column of the
      periaqueductal gray with N-methyl-D-aspartate bilaterally provoked the greatest
      increase in cortical blood flow (laser-Doppler flowmetry and/or microsphere
      flowmetry). The response was widespread over the entire neocortical regions,
      elicited in a dose-dependent manner, with little change in arterial blood
      pressure. The flow was increased effectively by a submaximal dose of the amino
      acid (1 mM, 100 nl), attaining a peak increase by 99 +/- 41% of the baseline
      level (mean +/- S.D., n = 30), and was associated with an enhancement of the
      cortical metabolic rate for oxygen by 51 +/- 26%. We then compared the flow
      increase with that induced by cold exposure (by 52 +/- 29%, n = 27), the latter
      response being tightly coupled to an enhanced metabolic rate for oxygen (by 41 +/
      23%). It was thus found that the increase in cortical blood flow provoked by the
      subdivision was dependent on the cerebrovasodilator mechanism that may be coupled
      to the cortical oxidative metabolism to the extent of one-half, and on certain
      other mechanisms for the remaining half. In view of the fact that this particular
      region serves to generate vigorous defence reactions that involve flight
      behaviour, the region should also help to meet the urgent demand for an increased
      cortical blood flow, so as to prepare for the possible generation of cortical
      hyperactivity in coping vigorously with a threatening emergency.

PMID- 8735236
TI  - Reduction of regional brain glucose metabolism following different durations of
      chronic ethanol consumption in mice: a selective effect on diencephalic
      structures.
AB  - The effects of chronic alcohol consumption on regional brain glucose metabolism
      were examined in Balb/c mice using the [14C]2-deoxyglucose autoradiographic
      technique. Animals were given a solution of 12% v/v ethanol as their only source
      of fluid for either 6, 12 or 18 months and compared to control groups receiving
      either an isocaloric solution or saccharose or tap water. Alterations of cerebral
      brain glucose metabolism were assessed in mice who were returned to a non
      alcoholic diet and allowed to freely explore a T-maze. The results showed that
      chronic ethanol consumption induced reductions of regional metabolic activity
      which were functions both of the duration of alcohol treatment and of the
      structure studied. Whereas a six month period of alcoholization did not induce
      any significant effects on metabolic activity, 12 months of treatment were
      necessary to induce the first observable and significant reductions in [14C]2
      deoxyglucose labelling. These effects were mainly limited to diencephalic
      structures such as the lateral mammillary nuclei and the anterodorsal thalamic
      nuclei. The cerebellum was also affected but to a lesser degree. After 18 months
      of alcoholization, a generalized spread of the metabolic reduction to the entire
      mammillary complex (lateral, medial and posterior nuclei) and to the thalamic
      nuclei was observed. This same duration of treatment was necessary to induce the
      first detectable decrease of metabolic activity in the hippocampus. In agreement
      with data from human neuropathology, these findings confirm the particular
      vulnerability of diencephalic structures to ethanol and suggest that damage
      limited to diencephalic regions rather than to hippocampal or cortical areas
      could be primarily responsible for the memory disorders observed in Korsakoff's
      syndrome.

PMID- 8735237
TI  - Non-cardiogenic pulmonary oedema after scorpion envenomation: a true entity?

PMID- 8735238
TI  - Reviews of venomous snake systematics in Toxicon.

PMID- 8735239
TI  - Taxonomic changes and toxinology: systematic revisions of the Asiatic cobras
      (Naja naja species complex)
AB  - Until recently, all Asiatic cobra populations were regarded as belonging to one
      single species, Naja naja. Recent revisions have shown that there are in fact at
      least 10 full species of Asiatic Naja. In order to allow the existing literature
      to be reconciled with these recent discoveries, an interpretation of the older
      nomenclature is provided. Problematic areas, especially concerning the species N.
      sumatrana and N. siamensis, are highlighted.

PMID- 8735240
TI  - 11-Oxo-tetrodotoxin and a specifically labelled 3H-tetrodotoxin.
AB  - Tetrodotoxin was oxidized to a hydrated aldehyde, 11-oxo-tetrodotoxin, which
      shares the specificity of tetrodotoxin for the Na+ channel of the isolated
      voltage-clamped frog skeletal muscle fiber, but is four to five times more
      potent. It binds to the solubilized Na+ channel of eel electroplax with a
      similarly higher potency, because of an equilibrium dissociation constant about
      0.25, and a dissociation rate constant 2.4 times slower than those for
      tetrodotoxin. 11-Oxo-tetrodotoxin can be reduced to regenerate a tetrodotoxin,
      which is chemically and biologically indistinguishable from the original
      tetrodotoxin. By reducing with tritiated sodium borohydride, a 3H marker can be
      inserted regiospecifically to yield 11-[3H]-tetrodotoxin. Because it has a
      defined specific activity of > 2.5 Ci/mmole, and a 3H marker which does not
      exchange with solvent proton, 11-[3H]-tetrodotoxin is an ideal tracer for
      tetrodotoxin. It may enable studies of problems which require higher signals
      and/or better stability of the marker than those obtainable from currently
      available tracer Na(+)-channel ligands.

PMID- 8735241
TI  - Evidence for isomerization in myotoxin a from the prairie rattlesnake (Crotalus
      viridis viridis).
AB  - Myotoxin a, from the venom of the prairie rattlesnake, Crotalus viridis viridis,
      exists as a temperature-dependent equilibrium of two interconverting forms.
      Reverse-phase high-performance liquid chromatography (RP-HPLC) shows that the two
      forms interconvert slowly enough at 25 degrees C to be seen as two separate peaks
      with a molar ratio of c. 1:4. Each peak can be isolated and individually injected
      to give the same two peaks in the same ratio of areas. The two peaks merge during
      chromatography at elevated temperatures, indicating an increase in the rate of
      interconversion. At low temperature, c. 5 degrees C, the individual peaks can be
      isolated and maintained for several days without reaching equilibrium. Mass
      analysis by matrix-assisted laser desorption ionization (MALDI) time-of-flight
      mass spectrometry shows that myotoxin a is present in both RP-HPLC peaks,
      suggesting that the two resolved forms are conformational isomers. Capillary zone
      electrophoresis (CZE) also shows two resolved, but interconvertible peaks over a
      range of pH values. Furthermore, RP-HPLC chromatograms of myotoxin a at
      concentrations from 0.013 mM to 0.41 mM maintain a consistent ratio of peak
      areas, without evidence of dimerization. Two-dimensional 1H-NMR nuclear
      Overhauser enhancement spectroscopy indicates the presence of a cis-proline
      peptide bond, consistent with an equilibrium mixture of cis-trans isomers;
      however, addition of peptidyl-prolyl cis-trans isomerase (PPI) does not enhance
      the rate of equilibration of the RP-HPLC peaks isolated at c. 5 degrees C.

PMID- 8735242
TI  - Effect of Leiurus quinquestriatus hebreus venom on calcium and deoxyglucose
      uptake in cultured cardiac cells.
AB  - The effects of scorpion venom Leiurus quinquestriatus hebreus were studied on
      cardiac cells grown in culture. The venom (30 micrograms/ml) increased
      significantly (P < 0.05) Ca2+ uptake into intact cardiocytes and to sarcoplasmic
      reticulum of skinned cells. [3H]Deoxyglucose uptake was also increased
      significantly (P < 0.05) in venom treated cardiocytes. It was found that
      fractions I and III of the venom, separated by gel filtration and ion exchange
      chromatography, are responsible for the increased Ca2+ uptake by the sarcoplasmic
      reticulum, whereas fraction IIb, III and IV are responsible for the accelerated
      rate of uptake of 45Ca and [3H]deoxyglucose by intact cells. Ca channel blockers
      prevented these effects and similar results were obtained by propranolol. Thus,
      it is concluded that the venom exerts its effect through activation of beta
      adrenoceptors which causes the opening of L-type Ca channels.

PMID- 8735243
TI  - Antagonism of glutamate receptors by a chromatographic fraction from the exudate
      of the sea anemone Phyllactis flosculifera.
AB  - In the search for new glutamate antagonists it seems promising to characterize
      the effects of venom from invertebrates that prey mainly on crustaceans. In this
      work, the exudate of the sea anemone Phyllactis flosculifera was used as a source
      of this type of compound. The action of chromatographic fraction D from P.
      flosculifera was tested upon microion-tophoretically evoked glutamate responses
      in intracellular recordings from central neurons of the land snail Zachrysia
      guanensis. Bath application of fraction D (2-8 mg/ml, n = 13) diminished both the
      excitatory and the inhibitory components of glutamate agonists in Z. guanensis
      neurons; this action was dose-dependent and partially reversible. Fraction D
      actions were also tested in the multiunit spontaneous and mechanically evoked
      responses of the glutamatergic junction between hair cells and afferent neurons
      of the axolotl Ambystoma tigrinum. Pressure ejection of fraction D in
      concentrations ranging from 0.5 to 2 mg/ml (n = 9) decreased the spontaneous and
      mechanically evoked activity of semicircular canal afferent neurons and the
      responses evoked by kainic acid and alpha-amino-3-hydroxy-5-methylisoxasole-4
      propionic acid. This action was also dose-dependent and partially reversible.
      These results indicate that fraction D acts as a glutamate receptor antagonist in
      snail and amphibian neurons. Further studies are required to characterize the
      active compounds responsible for this action and its specificity upon the
      subtypes of glutamate receptors.

PMID- 8735244
TI  - Effects of microcystin-LR on the partial reactions of the Na(+)-K+ pump of the
      gill of carp (Cyprinus carpio Linneo).
AB  - Several partial reactions of the Na(+)-K+ pump enzyme were studied in a
      microsomal fraction derived from the gill of carp (Cyprinus carpio Linneo). We
      tested the effect of three toxins [(i) microcystin-LR, (ii) microcystin-LR-like
      toxin component isolated from Microcystis aeruginosa culture and (iii) okadaic
      acid] on the phosphorylation, ouabain binding and ATPase activity of the Na(+)-K+
      pump. The K(+)-dependent hydrolysis of the Na(+)-dependent phosphorylation of
      Na(+)-K+ pump, as well the release of bound ouabain were inactivated in direct
      proportion to the amount of each toxin treatment. These results indicate that
      these toxins not only block the hydrolysis of phosphorylated protein at serine
      and threonine residues, but also inhibit the aspartic dephosphorylation step of
      the sodium pump enzymes. This inactivation could disrupt the ion homeostasis of
      the internal medium by blocking the gill function. The blockage of gill activity
      could be the cause of the massive fish death during blooms of M. aeruginosa.

PMID- 8735245
TI  - The effects of Duvernoy's gland secretion from the xenodontine colubrid
      Philodryas olfersii on striated muscle and the neuromuscular junction: partial
      characterization of a neuromuscular fraction.
AB  - The effect of Philodryas olfersii Duvernoy's secretion was studied in vivo in
      mice and chicks as well as in the mouse phrenic nerve-diaphragm and the chick
      biventer cervicis preparations. The whole secretion (20-40 micrograms/ml)
      increased the creatine kinase (CK) levels in mice but had no effect on the mouse
      phrenic nerve-diaphragm preparation. In the chick, the secretion caused head drop
      and paresia as well as irreversible blockade of the twitch-tension evoked by
      indirect stimulation in the chick biventer cervicis preparation (50% paralysis in
      34.5 +/- 2.7 min, n = 4). The secretion also caused muscle contracture (30% of
      the maximal twitch-tension generated) after a latency of nearly 9 min. Following
      fractionation on a Superose 12 FPLC column, the neuromuscular activity was
      recovered in the high mol. wt fraction (Peak I). At a concentration of 10
      micrograms/ml in the chick biventer cervicis preparation, Peak I caused 50%
      paralysis within 18.5 +/- 3.0 min (n = 4), and evoked a strong contracture (70%
      of the maximal twitch-tension generated). The contractile responses of the chick
      preparation to ACh and KCL were partially blocked (90%) by the whole secretion
      and totally blocked by Peak I. CK release was increased by the whole secretion
      but not by Peak I. The whole secretion also produced various degrees of muscle
      cell lysis and extensive widening of the intercellular spaces. The latter showed
      a loosely arranged membranous network. In general, Peak I caused only minor
      morphological alterations compared with the whole secretion, although these were
      still significantly different from those observed in the control preparations.
      The changes principally involved hypercontraction of the muscle fibers. Based on
      the above results, we conclude that Peak I contains the factor(s) responsible for
      the in vitro effects on neuromuscular transmission, whereas the direct myotoxic
      effect is apparently caused by at least one other component of the Duvernoy's
      secretion.

PMID- 8735247
TI  - Hemolytic activities of triterpene glycosides from the holothurian order
      Dendrochirotida: some trends in the evolution of this group of toxins.
AB  - Hemolysis and K+ loss from mouse erythrocytes, induced by triterpene glycosides
      and their derivatives from this order of sea cucumbers were studied. Sulfate
      groups, attached to position 4 of the first xylose residue and to position 6 of
      the third glucose residue of the branched pentaosides, having 3-O-methyl-groups
      in terminal monosaccharide moieties increase K+ loss. A sulfate group at C-4 of
      the first xylose residue increases the hemolytic activity while a sulfate at C-6
      of the third monosaccharide unit decreases it. A sulfate group at C-6 of terminal
      3-O-methylglucose drastically decreases the hemolytic activity and rate of K+
      loss. The presence of a sulfate group at the first xylose residue in glycosides
      having no 3-O-methyl group at the terminal monosaccharide decreases hemolytic
      activity and rate of K+ loss. The presence of the 16-ketone group in aglycones
      having the 7(8)-double bond significantly decreases activity. These results
      correlate with the previously proposed trends in evolution of sea cucumber
      glycosides from substances having sulfate groups at C-6 of glucose and 3-O
      methylglucose units to substances sulfated at C-4 of the first xylose or having
      no sulfate groups, and from substances with aglycone 16-ketone to substances
      having no oxygen functions in this position.

PMID- 8735246
TI  - Occurrence of paralytic toxin in Taiwanese crab Atergatopsis germaini.
AB  - Paralytic toxicity was detected by paralytic shellfish poison bioassay for all 17
      specimens of the xanthid crab A. germaini collected from northern Taiwan in
      November 1993. The average toxicity of crab specimens was 3809 +/- 2591 mouse
      units (mean +/- S.D.). The toxin was partially purified from ethanolic extract of
      the crab by ultrafiltration and Bio-Gel P-2 column chromatography.
      Electrophoresis, TLC, HPLC, ultraviolet spectrum and GC-MS analyses indicated
      that the crab toxin was composed of gonyautoxin 3 (50%), neosaxitoxin and
      saxitoxin (7%), a novel paralytic shellfish poison-like toxin (40%) and
      tetrodotoxin (3%).

PMID- 8735249
TI  - A biological method for the quantitative measurement of tetrodotoxin (TTX):
      tissue culture bioassay in combination with a water-soluble tetrazolium salt.
AB  - A tissue culture bioassay, using the mouse neuroblastoma cell line (Neuro2A), was
      improved to provide a simple and sensitive bioassay for TTX or sodium channel
      blocking toxins (SCB). The water-soluble tetrazolium salt, 2-(4-iodophenyl)-3-(4
      nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetraz olium, monosodium salt (WST-1), was
      applied to replace the time-consuming and subjective cell-counting procedure of
      the cells with automatic measurement, using a microplate reader. It was also
      confirmed that this method is directly applicable to bacterial culture
      supernatants, with the precaution of possible interference.

PMID- 8735248
TI  - LYS-49 phospholipase A2 homologs from venoms of Deinagkistrodon acutus and
      Trimeresurus mucrosquamatus have identical protein sequence.
AB  - The complete amino acid sequences of the Lys-49 PLA2s from the venom of
      Deinagkistrodon acutus (from Taiwan and China) and Trimeresurus mucrosquamatus
      (Taiwan habu) were solved by a facile cDNA cloning and sequencing method. The
      deduced amino acid sequences of the Lys-49 PLA2s of both venoms are identical,
      suggesting close phylogenic relationship between this two snake species of
      different genera. In addition, by cloning and cDNA sequencing, the mRNA coding
      for a Arg-49 PLA2 homolog of low expression level was also found in the venom
      gland of T. mucrosquamatus.

PMID- 8735250
TI  - Toxicity of jellyfish and sea-anemone venoms on cultured V79 cells.
AB  - Cnidarian toxins exert an influence on human activities and public health. The
      cytotoxicity of crude toxins (nematocyst and surrounding tissue venom) of
      Aequorea aequorea, Rhizostoma pulmo and Anemonia sulcata was assessed on V79
      cells. Rhizostoma pulmo and Anemonia sulcata crude venoms showed remarkable
      cytotoxicity and killed all treated cells at highest tested concentration within
      2 and 3 hr, respectively. Aequorea aequorea crude venom greatly affected growth
      rate during long-term experiments. No genotoxic effect was observed.

PMID- 8735251
TI  - A review of in vivo experimental methods to determine the composition of the
      human body.
AB  - This review of experimental methods employed in the measurement of the
      composition of the human body covers the developments that have occurred over the
      past 30 years. Early methods such as hydrodensitometry and skinfold anthropometry
      have been superseded by dual-energy x-ray absorptiometry and bioelectrical
      impedance spectroscopy. The measurement of the whole-body abundance of certain
      elements by isotopic dilution, neutron activation analysis and x-ray fluorescence
      can give important information of clinical significance, but neutron activation
      facilities remain available in only a few centres worldwide. The relatively
      simple, rapid and risk-free electrical methods such as multifrequency
      bioelectrical impedance analysis, which can be employed at the bedside, have been
      found to be more complicated in their interpretation. Electromagnetic methods may
      only measure the composition of the human body at its surface. X-ray computed
      tomography and magnetic resonance imaging have not yet been employed much in body
      composition measurements. Some models for the composition of the human body are
      reviewed.

PMID- 8735252
TI  - Photodynamic therapy with pulsed light sources: a theoretical analysis.
AB  - The effectiveness of photodynamic therapy using pulsed sources was evaluated
      using a mathematical model describing the time-dependent excitation and de
      excitation of the photosensitizer molecule. Using the various numerical data
      available in the literature on haematoporphyrin we calculated that the
      effectiveness of pulsed excitation in PDT is identical to that of CW excitation
      for peak fluence rates below 4 x 10(8) W m-2. Above this threshold the
      effectiveness drops significantly. In practice this effect will occur with
      sources with high pulse energy and low repetition frequency. The commonly used
      dye lasers pumped by either a Cu vapour laser or a frequency doubled Nd:YAG laser
      have a PDT effectiveness identical to that of a CW source of the same wavelength
      and the same average fluence rate.

PMID- 8735253
TI  - [Characterization of the response of hexagonal parallel-hole collimators of
      scintillation cameras].
AB  - This paper presents a formulation of the frequency response of hexagonal parallel
      hole collimator scintillation cameras. To describe this response, we propose an
      equation determined semi-empirically from a great number of simulations. The
      utility of the equation is that it enables the simple calculation of the response
      from collimator characteristics by taking into account the collimator's hexagonal
      structure. Because the equation does not assume translation invariance, the
      results can be directly compared with experimental measurements obtained with a
      point source. It is particularly interesting for collimators with large holes,
      like the medium-resolution ones used for high-energy radiation. Quality control
      and physical performance measurements are thus facilitated for this kind of
      collimator. Also, we present a new parameter that gives a quantitative assessment
      of the importance of partition penetration. This parameter is measured directly
      from the collimator frequency response. It has been studied by simulation, taking
      into account gamma photon attenuation in collimator partitions. The experimental
      measurements that have been made are in accord with the proposed equations.

PMID- 8735254
TI  - A description of discrete vessel segments in thermal modelling of tissues.
AB  - In hyperthermia treatment planning vessels with a diameter larger than 0.5 mm
      must be treated individually. Such vessels can be described as 3D curves with
      associated diameters. The temperature profile along the vessel is discretized one
      dimensionally. Separately the tissue is discretized three dimensionally on a
      regular grid of voxels. The vessel as well as the tissue are positioned in one
      global space. Methods are supplied to describe the tissue-vessel interaction, the
      shift of the blood temperature profile describing the flow of blood along the
      vessel and the calculation of the vessel wall temperature. The calculation of the
      interaction is based on tissue temperature samples and the blood temperature
      together with the distance between the centre of the vessel and the tissue
      temperature sample. An analytical expression for a vessel inside a coaxial tissue
      cylinder is then used for the calculation of the heat flow rate across the vessel
      wall. The basic test system is a vessel segment embedded inside a coaxial tissue
      cylinder. All the tests use this setup while the following simulation parameters
      are varied: position and orientation of the vessel relative to the tissue grid,
      vessel radius, sample density of the blood temperature and power deposition
      inside the tissue cylinder. The blood temperature profile is examined by
      calculation of the local estimate of the equilibration length. All tests show
      excellent agreement with the theory.

PMID- 8735255
TI  - The effect of free-electron collection on the recombination correction to
      ionization measurements of pulsed radiation.
AB  - Three models of the charge collection process in small dosimetric ionization
      chambers exposed to pulsed radiation are discussed. All three models allow for
      the presence of a free-electron component in the charge transfer, incorporating
      this into the model in slightly different ways, and the resulting collection
      efficiency formulae are compared over the range of variables normally met within
      clinical dosimetry. Measurements of the free-electron fraction for plane-parallel
      ionization chambers and for a Baldwin-Farmer 0.6 cm3 chamber are presented. The
      proportion of free electrons at the normal operating voltage is often high in
      small chambers but it is obvious that this can only lead to an increase in
      collection efficiency if the f-value calculated for purely ionic conduction
      allows for some improvement. Thus, a 50% free-electron fraction in a chamber
      which collects ions with efficiency f = 0.9950 at low pulse doses will increase
      this efficiency to only 0.9982. The same chamber, at the same operating voltage,
      and therefore the same free-electron fraction, if exposed to larger pulse doses,
      yielding an efficiency of 0.9531 as calculated for ions alone, would have a true
      efficiency of 0.9830-a large change.

PMID- 8735256
TI  - A patient dose survey for femoral arteriogram diagnostic radiographic
      examinations using a dose-area product meter.
AB  - We present a method for dealing with a complex radiographic procedure (which
      involves multiple radiographs and fluoroscopy) in an attempt to provide a simple
      way of calculating effective dose from which a general risk factor can be
      determined. A useful index of harm can be obtained by recording the number of
      radiographs in each region, and the fluoroscopy time, from which the effective
      dose may be easily calculated. A patient dose survey was carried out using a PTW
      diamentor for femoral arteriogram procedures in a large teaching hospital. The
      procedure involves fluoroscopy to the pelvic region to locate a guide wire and
      catheter, followed by a series of radiographs extending from the pelvic area to
      the feet to form a collage image of the entire arterial system. Radiographs are
      taken whilst a bolus of contrast media is injected into the arterial system.
      These measurements extend a continuing survey of doses for common diagnostic
      radiographic examinations which have previously included the simple examinations
      of lumbar spine, abdomen and pelvis.

PMID- 8735257
TI  - Automated analysis of mammographic densities.
AB  - Information derived from mammographic parenchymal patterns provides one of the
      strongest indicators of the risk of developing breast cancer. To address several
      limitations of subjective classification of mammographic parenchyma into coarse
      density categories, we have been investigating more quantitative, objective
      methods of analysing the film-screen mammogram. These include measures of the
      skewness of the image brightness histogram, and of image texture characterized by
      the fractal dimension. Both measures were found to be strongly correlated with
      radiologists' subjective classifications of mammographic parenchyma (Spearman
      correlation coefficients, Rs = -0.88 and -0.76 for skewness and fractal dimension
      measurements, respectively). Further, neither measure was strongly dependent on
      simulated changes in mammographic technique. Correlation with subjective
      classification of mammographic density was better when both the skewness and
      fractal measures were used in combination than when either was used alone. This
      suggests that each feature provides some independent information.

PMID- 8735258
TI  - The influence of a relaxation parameter on SPECT iterative reconstruction
      algorithms.
AB  - Algebraic reconstruction techniques (ARTs) have been intensively studied in image
      reconstruction. However, reconstructed images often exhibit a characteristic
      noise when applied to emission tomography. In this work, we study the influence
      of the ART relaxation parameter and identify values of that parameter which yield
      smooth images and good convergence. The study includes both simulated and real
      single photon emission computed tomographic (SPECT) data. In the simulated
      studies, scattering, attenuation, noise and detector response were included.
      Relaxation factors ranging between 0.01 and 0.35 were considered. Total counts in
      projections were between 2.5 x 10(5) and 10(6) in one slice. The goodness of the
      reconstructions was assessed by using the correlation coefficient between the
      pattern and the actual reconstruction (CC), the background coefficient of
      variation (CV), the contrast (CON) and the signal-to-noise ratio (SNR). The
      results show that values for the relaxation factor and number of interations
      close to 0.1 and 8, respectively, yield reconstructed images in which CC, CV, CON
      and SNR have well balanced values and CC, CV and SNR are very close to the
      extremal. An increase in either the number of iterations or in the relaxation
      factor results in a rise of CON but the other three FOMs deteriorate. The results
      from the real phantom, which are in agreement with those of the simulated
      studies, validate the simulation method and demonstrate the influence of the
      relaxation parameter.

PMID- 8735259
TI  - Measurement of tissue temporal point spread function (TPSF) by use of a gain
      modulated avalanche photodiode detector.
AB  - This paper describes an opto-electronic cross-correlator designed for measurement
      of the temporal point spread function (TPSF) of light at the bedside. Ultra-short
      (< 2 ps) pulses of light from a mode-locked laser were used to illuminate a
      tissue phantom. The light exiting from the tissue phantom was coupled by an
      optical fibre to a small-area (200 microns diameter, Hamamatsu S2381) avalanche
      photodiode (APD). The gain of the photodiode was modulated at the repetition rate
      of the pulsed laser (82 MHz). Usually the gain was approximately 100, but for a
      period of approximately 130 ps (FWHM) the gain was increased to approximately
      105. A lock-in amplifier, which sampled the integrated APD current, gave an
      output proportional to the difference between the current in the low- and high
      gain states. Hence a small section of the TPSF was selectively sampled. An
      overall temporal resolution of 275 ps FWHM was achieved. As the timing of the
      gain modulation was controlled by an all-electronic variable-time-delay system,
      the whole of the TPSF could be sampled without requiring any moving prism or
      mirror which is typical of many cross-correlators. Hence the system is
      mechanically very rugged, which enhances its durability in a portable instrument.

PMID- 8735260
TI  - Decoquinate and the control of experimental ovine toxoplasmosis.
AB  - Decoquinate was tested for its ability to reduce the effect of experimentally
      induced toxoplasmosis in pregnant ewes. Sheep were given decoquinate in their
      feed daily at either 2 mg or 1 mg/kg bodyweight from 10 days before an oral
      challenge with Toxoplasma gondii oocysts at 90 days of gestation, until lambing.
      Feeding decoquinate at the higher rate caused a delay in the onset of the febrile
      response to infection, reduced the overall severity of the fever and delayed the
      production of antibodies to the parasite. This treatment also reduced the
      placental damage caused by the parasite, lengthened the mean gestation period and
      increased the number and weight of live lambs, in comparison with ewes not fed
      decoquinate but challenged with T gondii oocysts. The treatment with 1 mg of
      decoquinate had smaller effects.

PMID- 8735262
TI  - Malignant histiocytosis in three Bernese mountain dogs.
AB  - Malignant histiocytosis is a rare disease which is characterised by the
      neoplastic proliferation of tissue macrophages (histiocytes) leading to excessive
      phagocytosis of erythrocytes. The clinical signs and pathological findings in
      three Bernese mountain dogs are described. Two of the dogs had the same sire. The
      disease has been established as a familial problem in Bernese mountain dogs in
      other countries, although it has not been previously recorded in the United
      Kingdom.

PMID- 8735261
TI  - Canine distemper virus in Lake Baikal seals (Phoca sibirica).
AB  - The virus epizootic which resulted in significant mortality in Siberian seals
      (Phoca sibirica) in Lake Baikal during 1987/88 was caused by canine distemper
      virus. Sequence analysis of the virus glycoprotein genes revealed that it was
      most closely related to recent European field isolates of canine distemper virus.
      This paper presents evidence that the same virus continued to circulate in seals
      in Lake Baikal after the initial epizootic. Three out of 45 brain tissue samples
      collected from seals culled in the spring of 1992 were positive for canine
      distemper virus-specific nucleic acid by the reverse transcription/polymerase
      chain reaction and the sequences were closely related to that of the original
      virus isolated in 1988.

PMID- 8735263
TI  - Use of PCR to detect Mycoplasma mycoides subspecies mycoides from nasal filter
      strips.

PMID- 8735264
TI  - Idiopathic moult in the African grey parrot (Psittacus erithacus) in a tropical
      environment.

PMID- 8735266
TI  - Emergency slaughter certificates for cattle over 30 months of age.

PMID- 8735265
TI  - Antigenic types of canine parvoviruses prevailing in Taiwan.

PMID- 8735267
TI  - LVIs and BSE control measures.

PMID- 8735268
TI  - Low bulk milk SCC and toxic mastitis.

PMID- 8735269
TI  - A structure/function analysis of Escherichia coli RNA polymerase.
AB  - Control of RNA polymerase is a common means of regulating gene expression. A
      detailed picture of both the structure and how the structural details of RNA
      polymerase encode function is a key to understanding the molecular strategies
      used to regulate RNA polymerase. We review here data which ascribes functions to
      some regions of the primary sequence of the subunits (alpha, beta beta' sigma)
      which make up E. coli RNA polymerase. We review both genetic and biochemical data
      which place regions of the primary sequence that are distant from one another in
      close proximity in the tertiary structure. Finally we discuss the implications of
      these findings on the quaternary structure of RNA polymerase.

PMID- 8735270
TI  - X-ray crystallographic studies of eukaryotic transcription initiation factors.
AB  - TATA box-binding protein (TBP) is required by all three eukaryotic RNA
      polymerases for correct initiation of transcription of ribosomal, messenger,
      small nuclear and transfer RNAs. Since the first gene encoding a TBP was cloned,
      it has been the object of considerable biochemical and genetic study. Substantial
      progress has also been made on structural and mechanistic studies, including our
      three-dimensional crystal structures of TBP, TBP bound to a consensus TATA
      elements, and the ternary complex of transcription factor IIB (TFIIB) recognizing
      TBP bound to a TATA element. The structure of apo TBP was determined at 2.1 A
      resolution. This highly symmetric alpha/beta structure represents a new DNA
      binding fold, which resembles a molecular "saddle' that sits astride the DNA. The
      DNA-binding surface is a novel curved, antiparallel beta-sheet. The structure of
      TBP complexed with the TATA element of the Adenovirus major late promoter was
      determined at 1.9 A resolution. Binding of the protein induces a dramatic
      conformational change in the DNA, by tracking the minor groove and inducing two
      sharp kinks at either end of the sequence TATAAAAG. Between the kinks, the right
      handed double helix is smoothly curved and partly unwound, presenting a widened
      minor groove to TBP's concave, antiparallel beta-sheet. Side chain-base
      interactions are completely restricted to the minor groove, and include hydrogen
      bonds, van der Waals contacts and phenylalanine-base stacking interactions. The
      structure of a TFIIB/TBP/TATA element ternary complex was determined at 2.7 A
      resolution. Core TFIIB resembles cyclinA, and recognizes the preformed TBP-DNA
      complex via protein-protein and protein-DNA interactions. The N-terminal domain
      of core TFIIB forms the downstream surface of the ternary complex, where it could
      fix the transcription start site. The remaining surfaces of TBP and the TFIIB can
      interact with TBP-associated factors, other class II initiation factors, and
      transcriptional activators and coactivators.

PMID- 8735271
TI  - The biochemistry of transcription in eukaryotes: a paradigm for multisubunit
      regulatory complexes.
AB  - The control of gene expression during development, differentiation and
      maintenance of cellular function is governed by a complex array of transcription
      factors. We have undertaken a molecular dissection of the regulatory factors that
      direct transcription of protein coding genes by RNA polymerase II. Our early
      studies identified sequence-specific transcriptional activators that bind to
      enhancer and promoter sequences to modulate the transcriptional initiation event.
      However, the mechanism by which activators enhance transcription and mediate
      promoter selectivity remained unknown. Combining biochemical purification and in
      vitro assays, we have recently identified an essential class of transcription
      factors called TAFs that are tightly associated with the basal factor TBP (TATA
      binding protein). We have found that TAFs are responsible for at least two
      regulatory functions. Some TAFs serve as coactivators capable of binding
      activators and mediating enhancing function. Other TAFs have been shown to confer
      template selectivity by binding directly to core DNA elements of the promoter.
      Thus different subunits of TBP/TAF complexes perform a variety of functions
      critical for transcriptional regulation in animal cells.

PMID- 8735272
TI  - Towards an understanding of protein-DNA recognition.
AB  - Understanding how proteins recognize DNA in a sequence-specific manner is central
      to our understanding of the regulation of transcription and other cellular
      processes. In this article we review the principles of DNA recognition that have
      emerged from the large number of high-resolution crystal structures determined
      over the last 10 years. The DNA-binding domains of transcription factors exhibit
      surprisingly diverse protein architectures, yet all achieve a precise
      complementarity of shape facilitating specific chemical recognition of their
      particular DNA targets. Although general rules for recognition can be derived,
      the complex nature of the recognition mechanism precludes a simple recognition
      code. In particular, it has become evident that the structure and flexibility of
      DNA and contacts mediated by water molecules contribute to the recognition
      process. Nevertheless, based on known structures it has proven possible to design
      proteins with novel recognition specificities. Despite this considerable
      practical success, the thermodynamic and kinetic properties of protein/DNA
      recognition remain poorly understood.

PMID- 8735273
TI  - Activation and repression of gene expression by POU family transcription factors.
AB  - The POU family transcription factors Oct-2 and Brn-3 utilize different mechanisms
      to produce a variety of effects on gene expression particularly in the nervous
      system. In the case of Oct-2, a single gene produces a primary RNA transcript.
      This transcript then undergoes alternative splicing to yield a variety of
      different mRNAs encoding Oct-2 isoforms which either activate or repress gene
      expression. In contrast, three distinct genes encode the closely related Brn-3
      factors, Brn-3b, Brn-3b and Brn-3c. Although the proteins encoded by the Brn-3a
      and Brn-3c genes activate their target genes Brn-3b represses these genes and can
      also interfere with activation by Brn-3a or c. These finding indicate that
      diverse mechanisms are used to generate activating or repressing forms of POU
      family transcription factors.

PMID- 8735274
TI  - Mechanisms of transcriptional activation and repression can both involve TFIID.
AB  - Regulation of transcription involves the activities of activators and repressors.
      Recent experiments have provided evidence that the function of both types of
      regulators can involve interactions with one or more component of the basal
      transcription machinery. A principal target appears to be TFIID, which consists
      of the TATA binding protein (TBP) and associated factors (TAFs). Here we describe
      experiments that provide added support for the idea that interactions affecting
      TFIID can play important roles in both activation and repression. We show, using
      transfection assays in Drosophila Schneider cells, that recruitment of TBP to a
      promoter as a GAL4-TBP fusion protein can provide a substantial activation of
      transcription. The conserved core of TBP is necessary and sufficient for this
      effect, which was observed with both TATA-containing and TATA-lacking basal
      promoters. These findings extend experiments performed in yeast, and strengthen
      the idea that recruitment of TBP (TFIID) can be an important mechanism of
      activation. We also provide further support for the idea that TBP can be a target
      for a transcriptional repressor, the Drosophila Even-skipped protein (Eve). We
      present evidence that the homeodomain, which is necessary for binding TBP in
      vitro, can also be required for repression in vivo, independent of its role in
      DNA binding. On the other hand, deletion of the alanine/proline-rich region that
      is essential for repression in vivo and TBP binding in vitro does not
      significantly affect DNA binding by the purified protein. These results
      strengthen the view that TBP, either directly or indirectly as a component of
      TFIID, can be a target of both activators and repressors.

PMID- 8735275
TI  - Structure and function of Escherichia coli met repressor: similarities and
      contrasts with trp repressor.
AB  - Transcription of genes encoding enzymes for the biosynthesis of methionine and
      trytophan in Escherichia coli is regulated by the ligand-activated met and trp
      repressors. X-ray crystallographic studies show how these two small proteins,
      although similar in size and function, have totally different three-dimensional
      structures and specifically recognize their respective DNA operator sequences in
      different ways. A common feature is that both repressors bind as cooperative
      arrays to tandem repeats of 8 base-pair 'Met' or 'Trp boxes' respectively, and
      the consensus sequences share the rare tetranucleotide CTAG. A series of
      structural and functional studies have shown how the two repressors discriminate
      between their operators, using a combination of direct contacts between side
      chains and bases, and indirect sensing of conformational properties of the DNA.

PMID- 8735276
TI  - Control of the cell-specificity of sigma F activity in Bacillus subtilis.
AB  - Sporulation in Bacillus subtilis is a simple developmental system involving the
      differentiation of two cell types that are formed by an asymmetric cell division.
      Major changes in the pattern of transcription during sporulation are brought
      about by the synthesis of new sigma factors (sigma), which are subunits of RNA
      polymerase that determine promoter specificity. Transcription in the smaller
      prespore cell type is initiated by a sigma factor called sigma F, the activity of
      which is subject to tight spatial and temporal control. It is negatively
      regulated by an anti-sigma factor, SpoIIAB, which is in turn controlled by an
      anti-anti-sigma factor, SpoIIAA. SpoIIAA and SpoIIAB participate in two
      contrasting reactions in vitro. In the presence of ATP, the proteins interact
      transiently and SpoIIAA is inactivated by phosphorylation on a specific serine
      residue; SpoIIAA then remains free to inhibit sigma F. In the presence of ADP,
      SpoIIAA binds tightly to SpoIIAB, and sigma F is set free. Release of sigma F
      activity in vivo might thus be effected by a prespore-specific reduction in the
      ATP/ADP ratio. Genetic experiments have implicated a fourth protein, called
      SpoIIE, in this system. It now appears that SpoIIE has two important and
      independent functions in the establishment of the prespore-specific transcription
      by sigma F. First it regulates sigma F activity, probably acting as a phosphatase
      to regenerate the active, non-phosphorylated form of SpoIIAA. Second it controls
      the formation of the septum that generates the prespore compartment. Combination
      of these two functions in a single polypeptide may provide a means of coupling
      gene expression with morphogenesis.

PMID- 8735277
TI  - Protein-protein interactions during transcription activation: the case of the
      Escherichia coli cyclic AMP receptor protein.
AB  - The Escherichia coli cyclic AMP receptor protein (CRP) is a homodimeric
      transcription activator triggered by cyclic AMP. Escherichia coli contains more
      than 100 different promoters that can be activated by CRP: in most cases the CRP
      acts by making direct contact with RNA polymerase. Remarkably, there is
      considerable variation in the location of the DNA site for CRP from one CRP
      dependent promoter to another. Genetic methods have been used to locate the
      activating regions of CRP that make contact with RNA polymerase at promoters of
      different architectures. At promoters where the DNA site for CRP is centred near
      to positions -61, -71 or -81 (i.e. 61, 71 or 81 base pairs upstream of the
      transcript start-point, respectively), a single surface-exposed loop (Activating
      Region 1) in the downstream subunit of the CRP dimer makes contact with RNA
      polymerase. The contact site in RNA polymerase is located in one of the C
      terminal domains of two RNA polymerase alpha subunits. At promoters where the DNA
      site for CRP is centred near to position-41, both subunits of the CRP dimer make
      contact with RNA polymerase via three separate surface exposed regions
      (Activating Regions 1, 2 and 3). At these promoters, where bound CRP overlaps
      with RNA polymerase-binding elements, the C-terminal domains of the polymerase
      alpha subunits are displaced and bind upstream of CRP. Activation at a number of
      E. coli promoters is dependent on binding of two CRP dimers, with one dimer bound
      near to position-41 and the other dimer bound further upstream. In these cases,
      both bound CRP dimers contact RNA polymerase. The CRP dimer bound around position
      41 contacts RNA polymerase via Activating Regions 1, 2 and 3, whereas the
      upstream bound CRP dimer contacts one of the displaced alpha C-terminal domains
      via Activating Region 1 in the downstream CRP subunit. Thus in these cases,
      codependence on two activators is due to simultaneous contacts between separate
      activators and RNA polymerase. This mechanism allows great flexibility, as any
      activator that can contact the C-terminal domain of the RNA polymerase alpha
      subunits can act cooperatively with CRP.

PMID- 8735278
TI  - Integration of growth factor signals at the c-fos serum response element.
AB  - A transcription factor ternary complex composed of serum response factor (SRF)
      and a second factor, ternary complex factor (TCF), mediates the response of the c
      fos Serum Response Element to growth factors and mitogens. In NIH3T3 fibroblasts,
      TCF binding is required for transcriptional activation by the SRE in response to
      activation of the Ras-Raf-ERK pathway. We compared the properties of three
      members of the TCF family, Elk-1, SAP-1 and SAP-2 (ERP/NET). Although all the
      proteins contain sequences required for ternary complex formation with SRF, only
      Elk-1 and SAP-1 appear to interact with the c-fos SRE efficiently in vivo. Each
      TCF contains a C-terminal activation domain capable of transcriptional activation
      in response to activation of the Ras-Raf-ERK pathway, and this is dependent on
      the integrity of S/T-P motifs conserved between all the TCF family members. In
      contrast, activation of the SRE by whole serum and the mitogenic phospholipid LPA
      requires SRF binding alone. Constitutively activated members of the Rho subfamily
      of Ras-like GTPases are also capable of inducing activation of the SRE in the
      absence of TCF; unlike activated Ras itself, these proteins do not activate the
      TCFs in NIH3T3 cells. At the SRE, SRF- and TCF-linked signalling pathways act
      synergistically to potentiate transcription.

PMID- 8735279
TI  - CREM: a master-switch in the transcriptional response to cAMP.
AB  - The CREM gene encodes both repressors and activators of cAMP-dependent
      transcription in a tissue and developmentally regulated manner. In addition,
      multiple and cooperative phosphorylation events regulate the function of the CREM
      proteins. CREM plays a key physiological and developmental role within the
      hypothalamic-pituitary axis. There is a functional switch in CREM expression
      during the development of male germ cells which is directed by the pituitary
      hormone FSH. The CREM protein in germ cells is a powerful activator which appears
      to function as a master-switch in the regulation of postmeiotic genes. CREM is
      inducible by activation of the cAMP signalling pathway with the kinetics of an
      early response gene. The induction is transient, cell-specific, does not involve
      increased transcript stability and does not require protein synthesis. The
      subsequent decline in CREM expression requires de novo protein synthesis. The
      induced transcript encodes ICER and is generated from an alternative, intronic
      promoter. ICER functions as a powerful repressor of cAMP-induced transcription,
      and represses the activity of its own promoter, thus constituting a negative
      autoregulatory loop.

PMID- 8735280
TI  - Ligand-dependent interaction of nuclear receptors with potential transcriptional
      intermediary factors (mediators).
AB  - The activity of the ligand-inducible activation function 2 (AF-2) contained in
      the ligand binding domain (LBD) of nuclear receptors (NRs) is thought to be
      mediated by transcriptional intermediary factors (TIFs). We have recently
      reported the isolation and characterization of two novel mouse proteins,
      designated TIF1 and mSUG1, that interact in a ligand-dependent fashion with the
      LBD (region E) of several NRs in vivo as well as in vitro. Remarkably, these
      interactions require the conserved core motif of the AF-2 activating domain (AF-2
      AD) and can be blocked by AF-2 antagonists. TIF1 and mSUG1 might therefore
      represent TIFs/mediators for the ligand-dependent AF-2 of NRs. By comparing the
      interaction properties of these two putative TIFs with different NRs including
      the oestrogen (ER), thyroid hormone (TR), vitamin D3 (VDR), retinoic acid (RAR
      alpha) and retinoid X (RXR) receptors, we demonstrate that: (i) RXR alpha
      efficiently interacts with TIF1, but not with mSUG1, whereas TR alpha interacts
      much more efficiently with mSUG1 than with TIF1, and RAR alpha, VDR and ER
      efficiently interact with both TIF1 and mSUG1; (ii) the amphipathic alpha helix
      core of AF-2 AD is differentially involved in the interactions of RAR alpha with
      TIF1 and mSUG1; and (iii) the AF-2 AD cores of RAR alpha and ER are similarly
      involved in their interaction with TIF1, but not with mSUG1. Thus the interaction
      interfaces between the various NRs and either TIF1 or mSUG1 may vary depending on
      the nature of both the receptor and the putative mediator of its AF-2 function.
      We discuss the possible roles of TIF1 and mSUG1 as mediators of the
      transcriptional activity of the AF-2 of NRs.

PMID- 8735281
TI  - Gene regulation in the Drosophila embryo.
AB  - Pattern formation in Drosophila depends on hierarchical interactions between the
      maternal and zygotic gene activities which subdivide the embryo into increasingly
      smaller metameric units along the anterior posterior axis. Here we describe those
      genes that encode the transcription factors which control precisely the
      expression of subordinate transcription factors in time and space. This
      regulation operates through the protein-protein interactions between
      transcription factors bound to the cis-acting enhancers, which eventually
      determine the frequency of transcription initiation by polymerase II. Our data
      show that taking into account the multiple transcriptional activators and
      repressors that bind to a typical enhancer element, it is likely that the
      regulation of gene expression in a given cell is defined by their concentration
      dependent interplay which directs target gene expression in a position-dependent
      fashion.

PMID- 8735282
TI  - The use of microwave irradiation as a pretreatment to in situ hybridization for
      the detection of measles virus and chicken anaemia virus in formalin-fixed
      paraffin-embedded tissue.
AB  - Microwave irradiation was investigated as a pretreatment to in situ hybridization
      on formalin-fixed, paraffin-embedded tissue. Two probe/tissue systems were used:
      a single-stranded RNA probe for the detection of measles virus nucleocapsid
      genome in subacute sclerosing panencephalitis brain tissue, and a double stranded
      DNA probe for chicken anaemia virus in thymus of chicken infected with the virus.
      Microwaving, when used as sole pretreatment, was not as effective as the more
      traditional enzyme pretreatments for in situ hybridization. However, when used in
      combination with existing pretreatments, a significant increase was found in
      hybridization signal in both brain and thymus tissue. This was emphasized when
      combination enzyme/microwave pretreatments were used prior to detection of
      measles virus by in situ hybridization in a series of five archival subacute
      sclerosing panencephalitis cases. The use of microwave irradiation would be
      recommended as a means of supplementing in situ hybridization methods, especially
      when using long-term formalin fixed paraffin-embedded tissue.

PMID- 8735283
TI  - Cytochemical distribution of cyclic AMP-dependent 3',5'-nucleotide
      phosphodiesterase in the rat myocardium.
AB  - The cytochemical localization of cAMP-dependent phosphodiesterase was studied in
      the rat myocardium. Slices 40 microns thick from perfusion-fixed rat hearts were
      incubated in the medium with cAMP as a substrate and Pb ions as a capture metal
      of the reaction product. After the incubation in the basic medium the specific
      precipitate of cAMP phosphodiesterase was localized on the sarcolemma of
      cardiomyocytes. In addition, it was localized on the plasmalemma of endothelial
      cells of capillaries and small coronary arteries as well as on the membrane of
      smooth muscle cells. Using selective inhibitors SK&F 94120 for phosphodiesterase
      III and Rolipram for the IV isoenzyme, both isoforms were detected on the
      membrane of smooth muscle cell. In addition, phosphodiesterase III was localized
      on the sarcolemma only and phosphodiesterase IV on the sarcolemma of
      cardiomyocytes and the plasmalemma of endothelial cells.

PMID- 8735284
TI  - Histochemical localization of zinc ions in the epididymis of the rat.
AB  - In the present study, the autometallograpic zinc sulphide technique, an improved
      version of the original Timm sulphide-silver method, was used. This technique
      reveals a particular pool of ionic zinc that is chelatable by
      diethyldithiocarbamate. At the light microscopical level, no reaction for zinc
      was found in tissues of young prepubertal rats. In adult mating and non-mating
      rats low zinc staining was found in the head and intermediate epididymis whereas
      the tail of the epididymis demonstrated high levels of zinc ions. Sections from
      the epididymal tail revealed a 'compartmentalization', based on pronounced
      differences in staining intensity along the epididymal ducts. At higher
      magnification zinc ions were found in the apical part of the principal cell and
      in the lumen. At the ultrastructural level autometallographic grains were located
      in vesicles and in lysosome-like structures of the apical parts of the principal
      cells. The luminal grains were found either associated with sperm cells, with the
      surface of the large microvilli (stereocilia), or free in the seminal fluid. The
      variation in content of zinc ions in the epididymal epithelium and lumen suggests
      that zinc ions are secreted into the lumen from the epididymal tail and may
      somehow be involved in maturation of the sperm cells.

PMID- 8735285
TI  - In situ determination of different dehydrogenase activity profiles in the linings
      of odontogenic keratocysts and radicular cysts.
AB  - The levels of succinate, lactate, glutamate, glycerophosphate and glucose-6
      phosphate dehydrogenases within the linings of keratinizing and non-keratinizing
      odontogenic cysts were investigated using static end-point and continuously
      monitored Nitroblue Tetrazolium-based histochemical methods. The use of TV image
      analysis for quantification of formazan final reaction products was validated by
      demonstrating significant relationships between the integrated absorbance at 585
      nm and the amount of formazan in, and thickness of, gelatin films containing
      reduced tetrazolium salt (r = 1.0, p < 0.001). Absorbance readings of stained
      sections gave mean coefficients of variation of 1.8 +/- 0.9% between day of
      measurement, and of 5.65 +/- 1.32% between serial sections. End-point assays
      indicated that the linings of odontogenic keratocysts contained higher levels of
      glucose-6-phosphate dehydrogenases (p < 0.0002) and lower levels of lactate
      dehydrogenase (p < 0.002) than those of radicular cysts. Succinate, glutamate and
      glycerophosphate dehydrogenase activities were similar in both cyst types.
      Results from continuously monitored assays, performed for glucose-6-phosphate and
      succinate dehydrogenases, demonstrated linear reaction rates over the first 2.75
      min of reaction. The calculated enzyme activities from continuous assays were
      between 1.49 and 3.49 times higher than those determined from end-point assays
      and confirmed that levels of glucose-6-phosphate dehydrogenase were significantly
      higher in the linings of odontogenic keratocysts than those of radicular cysts (p
      < 0.004). By contrast, succinate dehydrogenase activity was significantly higher
      in radicular cyst linings (p < 0.03). These results highlight the benefits of an
      approach to in situ determination of enzyme activity using image analysis and
      continuous monitoring methodologies. Overall, the high level of glucose-6
      phosphate dehydrogenase found in keratocyst linings is consistent with their
      clinical behaviour and higher level of proliferation and synthetic activity
      whereas the level of lactate dehydrogenase in radicular cysts probably reflects
      the presence of local tissue damage within these inflammatory lesions.

PMID- 8735286
TI  - Localization of tartrate-resistant acid phosphatase in human placenta.
AB  - Tartrate-resistant acid phosphatase is an inducible marker of cell
      differentiation and activation expressed by specialized cells of macrophage
      lineage and some activated lymphocytes. Clinically, this phosphatase is a
      diagnostic marker for hairy cell leukaemia and osteoclast activity. The cDNA for
      this enzyme has been cloned from a placental expression library, yet the cell(s)
      expressing the enzyme protein has not been determined with certainty. Our
      laboratories have developed a monoclonal antibody, 9C5, suitable for
      immunohistochemical localization of tartrate-resistant acid phosphatase in
      paraffin sections. The purpose of this study was to use antibody 9C5 to identify
      cells expressing tartrate-resistant acid phosphatase in sections of paraffin
      embedded, normal, full-term placenta and to determine if those cells expressed
      other macrophage markers including CD68 (PG-M1 antibody), LN5, lysozyme, alpha 1
      antitrypsin and alpha 1-antichymotrypsin. Histochemical localization of activity
      in frozen sections was compared with immunohistochemical localization in paraffin
      sections of the same tissue specimens. The activity and antigenicity of this
      enzyme were detected in decidual cells, syncytiotrophoblast, and some macrophages
      distributed throughout maternal and embryonic tissues, but not in neutrophils.
      Unlike other tissues previously examined, placenta contains significant numbers
      of the phosphate-positive cells that are not of macrophage origin.

PMID- 8735287
TI  - An immunohistochemical study of the 32-kDa galectin (beta-galactoside-binding
      lectin) in the nematode Caenorhabditis elegans.
AB  - The localization of the 32-kDa galectin (beta-galactoside-binding lectin) of the
      nematode Caenorhabditis elegans, which is the first lectin to be found in a
      nematode, was examined immunohistochemically using an anti-lectin antiserum. The
      lectin was found to be localized most abundantly in the adult cuticle and also in
      the terminal bulb of the pharynx. However, it was difficult to locate the
      galectin in larval animals, though immunochemical experiments suggested its
      presence. These results suggest that one of the fundamental roles of the galectin
      may be as a component of the durable outer barrier, as in the case of the
      morphogenesis of chick embryonic skin.

PMID- 8735288
TI  - Regional differences in uteroglobin biosynthesis along the rabbit oviduct:
      immunohistochemical and biochemical studies.
AB  - The biosynthesis of uteroglobin in three regions of the rabbit oviduct was
      assessed by means of immunocytochemical studies, radioimmunoassay measurements of
      the protein, and quantitative determinations of its mRNA. Immunocytochemical
      observations suggested that the number of immunopositive cells and the intensity
      of their immunolabelling were similar in the distal (infundibular) and the middle
      regions. In contrast, the isthmic portion appeared to contain less positive cells
      and weaker immunolabelling. In agreement with these findings, biochemical studies
      demonstrated that the tissue contents of uteroglobin and its mRNA were similar in
      the distal and the middle regions whereas the concentrations of both were about
      three-to four-fold lower in the isthmic portion. The results are discussed in
      relation to a possible role for uteroglobin in maintaining appropriate
      environmental conditions for the gametes and the early embryo.

PMID- 8735289
TI  - Histochemical localization of autometallographically detectable mercury in
      tissues of the immune system from mice exposed to mercuric chloride.
AB  - The distribution of mercury in the spleen, liver, lymph nodes, thymus and bone
      marrow was studied by autometallography in mice exposed to mercuric chloride
      intraperitoneally. Application of immunofluorescence histochemistry and an
      autometallographic silver amplification method was employed to the same tissue
      section. Mercury was not only detected in macrophages marked by the antibody
      M1/70 but also in macrophage-like cells, which were either autofluorescent or
      devoid of fluorescent signals. These two cell types were identified as
      macrophages at the electron microscopical level. Autometallographically stained
      macrophages were observed in the spleen, lymph nodes, thymus and in Kupffer cells
      of the liver. Furthermore, mercury was observed in endothelial cells. No obvious
      pathological disturbances were observed at light and electron microscopical
      level. At the subcellular level mercury was localized in lysosomes of macrophages
      and endothelial cells.

PMID- 8735290
TI  - Plasma glucose and pre-eclampsia.
AB  - OBJECTIVE: To determine whether there is a relationship between plasma glucose
      level in a glucose screening test and the occurrence of pre-eclampsia in non
      diabetic pregnant women. METHODS: All pregnant non-diabetic women attending the
      antenatal clinic at the Aga Khan University Medical Center were screened with a
      75 g-2 h glucose challenge test (GCT). From 1988-90, a data base of 1316 cases
      was compiled for use in this study. Of these, 67 had to be excluded because of
      one or more abnormal levels in the 75 g-3 h oral glucose tolerance test (GTT)
      that required treatment to maintain euglycemia. Among the remaining patients (n =
      1249) who had no evidence of glucose intolerance and were included in the
      analysis, there were 42 cases of pre-eclampsia. The association between pre
      eclampsia and plasma glucose level in the GCT was evaluated using logistic
      regression analysis that adjusted for effects of age and gravidity. RESULTS: The
      odds of having pre-eclampsia were increased by 20% (95% confidence interval 0%
      44%) per mmol/l rise in plasma glucose level in the GCT. The same statistic for
      age was 9% (95% confidence interval 2%-17%), and for primigravidity it was 210%
      (95% confidence interval 55%-517%). There was no significant interaction between
      these variables. CONCLUSIONS: Minor degrees of glucose intolerance, age and
      primigravidity are associated with a higher occurrence of pre-eclampsia in non
      diabetic pregnant women.

PMID- 8735291
TI  - Determinants of pregnancy outcome in patients with gestational diabetes.
AB  - OBJECTIVES: To describe the experience of management of gestational diabetes
      'GDM' among a high-risk population and to determine the relative contribution of
      maternal risk factors and some indices of glucose intolerance on pregnancy
      outcome. METHODS: A total of 173 antenatal patients with GDM, matched to 337 non
      diabetic controls were evaluated. Incidences of fetal macrosomia, large birth
      weight (> 4000 g), and operative delivery were noted. Patients with GDM were
      subgrouped into group I and II, according to the fasting blood glucose (FBG)
      level on the glucose tolerance test 'GTT', whether > or = or < 5.8 mmol/l,
      respectively. A logistic regression model was then developed with predictive
      variables, i.e. maternal weight, height, parity, gestational week at diagnosis of
      GDM, degree of glucose tolerance, treatment and means of fasting and post
      prandial blood glucose measurements as independent variables against each of the
      outcome measures as dependent variables. RESULTS: Compared with non-diabetics,
      patients with GDM were older in age, weight and parity. The mean fetal birth
      weight, incidences of macrosomia and babies > 4 kg were significantly higher
      among GDM patients. In patients with GDM the degree of glucose intolerance
      (determined by FBG on the GTT) and maternal weight were the only variables that
      significantly increased the risk of macrosomia and operative delivery. Within
      group I patients (FBG > or = 5.8 mg/dl) only 'maternal weight' significantly
      increased the risk of both having a baby > 4 kg, and operative delivery.
      CONCLUSION: Among patients with gestational diabetes, a GTT with a FBG level > or
      = 5.8 mmol/l is a strong predictor for perinatal outcome. Maternal weight is an
      independent risk factor that increases the risk of both macrosomia and operative
      delivery.

PMID- 8735292
TI  - Epidural analgesia as a risk factor for operative delivery.
AB  - OBJECTIVE: To study the relationship between epidural analgesia and instrumental
      and non-elective cesarean delivery in the 1990s in Finland. METHODS: The data was
      extracted from a nationwide birth register in 1991-1993. To adjust for other
      factors, hospital-based analyses were made separately for different types of
      hospitals and in individual-based analyses logistic regression was used. RESULTS:
      In the hospital-based analyses there was no systematic correlation between rates
      of epidural analgesia and operative delivery, but on the individual level there
      was. Comparison of hospitals with different levels of epidural rates and
      different types of hospitals suggests that the contradictory findings in the
      hospital and individual-based analyses are partly due to selection bias, and
      partly to different hospital policies. CONCLUSIONS: The results in previous
      studies and our results suggest that epidural analgesia is a risk factor for an
      operative delivery, but not a sufficient one, and its impact is likely to be
      modified by other obstetric practices and interventions.

PMID- 8735293
TI  - Granuloma inguinale in association with pregnancy and HIV infection.
AB  - OBJECTIVES: A retrospective study to confirm the clinical impression of an
      increasing prevalence of granuloma inguinale (GI) in women, and to evaluate its
      association with pregnancy and HIV infection. METHODS: Clinical records of all
      patients with a definitive diagnosis of GI attending the gynecology and antenatal
      clinics at King Edward VIII Hospital, Durban, South Africa, over a period of 36
      months (January 1991-December 1993). RESULTS: A total of 123 women were diagnosed
      with GI. The diagnosis was made by tissue smear alone in 21% (n = 26), histology
      43% (n = 53) and by a combination of smear and histology in the rest. Forty-two
      percent (n = 52) were pregnant. The only difference between pregnant and non
      pregnant women were the presence of rectal and pelvic lesions in the latter.
      Sixty-nine percent (n = 36) delivered vaginally while the remaining (n = 16) were
      delivered by cesarean section. The indications for cesarean section were
      obstetric except for a patient in labor with extensive untreated vulval
      granuloma. In the majority (85%) GI had no influence on pregnancy outcome. There
      was no evidence of congenital GI in the neonates. Twenty-seven percent (30/113)
      had positive syphilis serology and 16% (18/110) had antibody to HIV. There were
      no differences in the clinical features and outcome of HIV positive and negative
      women. CONCLUSION: This study shows that GI is increasing in pregnancy in Durban,
      South Africa. Despite the concern that pregnancy promotes dissemination of GI,
      such an effect could not be established as the clinical response to treatment and
      outcome were similar in both pregnant and non-pregnant women. Infection with HIV
      also did not alter the clinical presentation and outcome of the disease in the
      patients studied.

PMID- 8735294
TI  - Long-term follow-up of women with borderline ovarian tumors.
AB  - OBJECTIVE: To examine the long-term survival of patients with borderline ovarian
      carcinomas. METHOD: A population-based retrospective analysis of patients
      registered with West Midlands Regional Cancer Registry. The files of all patients
      registered with ovarian carcinoma during the triennium 1985-1987 were examined
      and those with borderline ovarian carcinomas identified. RESULTS: During the
      period, 1654 patients were registered, of whom 1344 had histologically confirmed
      ovarian carcinoma. From these 54 (4%) patients had borderline tumors--all Stage I
      or II. Follow-up ranged from 5 to 10 years, with only 2 patients identified where
      death was due to recurrent ovarian malignancy. CONCLUSIONS: Epidemiological
      studies avoid the bias associated with hospital-based series, and enable a crude
      evaluation of practice standards. From this series certain areas were identified
      where management could be improved. Thus the information gleaned can be utilized
      to address such issues, and comparative studies performed in the future to assess
      the impact of any changes made. The series confirms the excellent prognosis
      associated with early stage borderline ovarian carcinomas.

PMID- 8735295
TI  - Laparoscopy for adhesion prevention following myomectomy.
AB  - OBJECTIVE: To evaluate adhesion formation after classic abdominal myomectomy and
      the role of early, second-look laparoscopic adhesiolysis in the management of
      post-myomectomic pelvic adhesions in a prospective study. METHOD: Forty-eight
      patients with infertility, recurrent abortion or symptomatic myoma underwent
      second-look laparoscopy (SLL) 8 days after abdominal myomectomy. The degree of
      adnexal adhesions were scored according to the American Fertility Society
      Classification and were lyzed laparoscopically. The success of the SLL was
      evaluated in 18 patients who underwent a third-look procedure (cesarean section
      or laparoscopy) RESULTS: Myomectomy incisions on the posterior uterine wall were
      associated with more adhesions than that on the fundus or anterior wall (P <
      0.01). Myomectomies performed on uteri larger than 13 weeks gestation resulted in
      significantly higher adhesion scores than smaller ones (P < 0.001) and mainly
      intra-mural myomas than only sub-serous ones (P < 0.01). More than one uterine
      incision was found to result in more adhesions (P < 0.05), while the number of
      myomas removed were not found to affect adhesion formation (P > 0.05). In the
      patients who underwent a third-look procedure, adhesion scores were found to be
      significantly lower than the SLL (6.2 +/- 6.4 vs. 3.1 +/- 3.4) (P < 0.01).
      CONCLUSION: Myomectomy operations frequently result in pelvic adhesions, which
      may impair fertility. Early laparoscopy and adhesiolysis after myomectomy is
      useful for assessing the degree of adhesions, technical ease in performing
      adhesiolysis and resulting in lower adhesion scores as shown by third-look
      procedures.

PMID- 8735296
TI  - Malignant ovarian germ cell tumors.
AB  - OBJECTIVES: Fifty patients with malignant ovarian germ cell tumors, which
      accounts for 10.8% of all ovarian malignancies, were treated from 1977 through
      1994. Their cases are reviewed. METHODS: The histology includes endodermal sinus
      tumor (EST) in 15 patients, immature teratoma in 14, dysgerminoma in 13, and
      mixed germ cell tumor in eight. The mean age at presentation was 21.5 years and
      mean primary tumor diameter was 16 cm. All patients underwent surgery as the
      initial treatment, and 10 received more than one operation. Postoperative
      adjuvant chemotherapy was not given to cases with stage Ia immature teratoma and
      dysgerminoma. VAC (vincristine, actinomycin D, cyclophosphamide) and BVP
      (bleomycin, vinblastine, cisplatin) regimens were utilized in early 1980s for EST
      and advanced-stage tumors of immature teratoma and dysgerminoma. BEP (bleomycin,
      etoposide, cisplatin) and EP (etoposide, cisplatin) regimens were applied in
      advanced-stage disease and some stage I disease since 1990. VIP (VP-16,
      ifosfamide, cisplatin) regimen was employed as salvage regimen in cases where
      other combinations failed. RESULTS: alpha-Fetoprotein (AFP) was elevated in every
      tumor containing endodermal sinus element, and AFP served as a good indicator for
      prediction of tumor recurrence. The follow-up time ranged from 5 to 144 months
      with the mean of 54.5 months. CONCLUSIONS: The survival rate for EST was 54%,
      that for immature teratoma and dysgerminoma was 85% and 90%, respectively.

PMID- 8735297
TI  - Age of natural menopause among women in Mexico City.
AB  - OBJECTIVES: The average age of menopause among women in Mexico City was
      calculated, considering their reproductive and socio-demographic characteristics.
      The information was obtained from a population-based control group from a case
      controlled study of gynecologic cancer. METHODS: Interviews were carried out with
      1005 women resident in Mexico City chosen at random from a sample using the
      housing sample framework of the Mexico General Directorate of Epidemiology, 472
      of whom had undergone a natural menopause. RESULTS: The most important results
      include an average age for menopause in this population of 46.5 +/- 5 years (95%
      C.I. 46-48) with a median of 47. Groups of women with an average early menopause
      were those with no formal education (1.6 years), low socio-economic level (1.3
      years, P < 0.05), nulliparas (2.6 years, P < 0.05), those who had never breastfed
      (2.2 years, P < 0.05) and those who had not used contraceptive hormones (1.7
      years, P < 0.05). CONCLUSION: This phenomenon must be documented in Mexico
      because of its strong links with the morbidity and mortality of the growing
      number of women who are reaching advanced ages and whose survival is calculated
      at 30 years after menopause.

PMID- 8735299
TI  - Adenoma malignum of the uterine cervix associated with Peutz-Jeghers syndrome.

PMID- 8735298
TI  - Second trimester ovarian pregnancy.

PMID- 8735300
TI  - Combined intra-uterine and cervical pregnancy treated successfully with
      methotrexate.

PMID- 8735301
TI  - ACOG technical bulletin. Hypertension in pregnancy. Number 219--January 1996
      (replaces no. 91, February 1986). Committee on Technical Bulletins of the
      American College of Obstetricians and Gynecologists.

PMID- 8735302
TI  - ACOG technical bulletin. Hemoglobinopathies in pregnancy. Number 220--February
      1996 (replaces no. 185, October 1993). Committee on Technical Bulletins of the
      American College of Obstetricians and Gynecologists.
AB  - Hemoglobinopathies, while relatively uncommon among obstetric patients, can be
      associated with a variety of effects on the mother, fetus, or newborn. The
      effects range from absence of clinical disease to severe morbidity and death.
      Through the obstetrician-gynecologist's high index of suspicion based on clinical
      history and a close working relationship with a consultant hematologist,
      pregnancy outcome in patients with these disorders can be improved. Since most
      hemoglobinopathies are inherited as autosomal recessive conditions, screening,
      counseling, and prenatal diagnosis are important components of prenatal care for
      these women.

PMID- 8735303
TI  - ACOG committee opinion. Genetic screening for hemoglobinopathies. Number 168,
      February 1996. Committee on Genetics. American College of Obstetricians and
      Gynecologists.

PMID- 8735304
TI  - ACOG committee opinion. Tamoxifen and endometrial cancer. Number 169, February
      1996. Committee on Gynecologic Practice. American College of Obstetricians and
      Gynecologists.

PMID- 8735305
TI  - ACOG criteria set. Repeat cesarean delivery. Number 13, December 1995. Committee
      on Quality Assessment. American College of Obstetricians and Gynecologists.

PMID- 8735306
TI  - ACOG criteria set. Excisional breast biopsy. Number 14, January 1996. Committee
      on Quality Assessment.

PMID- 8735307
TI  - The Norwegian diet during the last hundred years in relation to coronary heart
      disease.
AB  - OBJECTIVE: The influence of dietary changes on serum cholesterol and CHD during
      the last century in Norway has been evaluated. DESIGN: Data on food consumption
      are based on national food supply and household consumption surveys. To be able
      to calculate comparable series of the dietary content of energy, fat, saturated,
      monounsaturated and polyunsaturated fatty acids and dietary cholesterol, we
      compiled food composition data covering this century. The dietary effect on serum
      cholesterol was estimated by Keys equation. RESULTS: Changes in dietary lipids
      precede the increase and the decrease in mortality of CHD. The estimated serum
      cholesterol level in the population increased by approximately 1 mmol/l during
      1900-1960, and decreased by approximately 0.6 mmol/l during 1960-1992. These
      changes correspond to a 60% increase and a 30% decrease in risk for CHD. However,
      the observed change in mortality of CHD was greater. During 1951-1955 and 1971
      1975 it increased by 120% in men and 80% in women aged 50-59 years and during
      1971-1975 and 1991-1993 it decreased by 43% and 29%, respectively. CONCLUSIONS:
      Change in dietary lipids have the potential to explain a great deal of the
      changes in mortality of CHD in Norway during this century. A reduced consumption
      of boiled coffee and an increase in the consumption of antioxidants may also have
      contributed to the reduced mortality of CHD the last 20 years.

PMID- 8735308
TI  - Free-living energy expenditure assessed by two different methods in rural Gambian
      men.
AB  - OBJECTIVE: To assess total free-living energy expenditure (EE) in Gambian farmers
      with two independent methods, and to determine the most realistic free-living EE
      and physical activity in order to establish energy requirements for rural
      populations in developing countries. DESIGN: In this cross-sectional study two
      methods were applied at the same time. SETTING: Three rural villages and Dunn
      Nutrition Centre Keneba, MRC, The Gambia. SUBJECTS: Eight healthy, male subjects
      were recruited from three rural Gambian villages in the sub-Sahelian area (age:
      25 +/- 4y; weight: 61.2 +/- 10.1 kg; height: 169.5 +/- 6.5 cm, body mass index:
      21.2 +/- 2.5 kg/m2). INTERVENTION: We assessed free-living EE with two
      inconspicuous and independent methods: the first one used doubly labeled water
      (DLW) (2H2 18O) over a period of 12 days, whereas the second one was based on
      continuous heart rate (HR) measurements on two to three days using individual
      regression lines (HR vs EE) established by indirect calorimetry in a respiration
      chamber. Isotopic dilution of deuterium (2H2O) was also used to assess total body
      water and hence fat-free mass (FFM). RESULTS: EE assessed by DLW was found to be
      3880 +/- 994 kcal/day (16.2 +/- 4.2 MJ/day). Expressed per unit body weight the
      EE averaged 64.2 +/- 9.3 kcal/kg/d (269 +/- 38 kJ/kg/d). These results were
      consistent with the EE results assessed by HR: 3847 +/- 605 kcal/d (16.1 +/- 2.5
      MJ/d) or 63.4 +/- 8.2 kcal/kg/d (265 +/- 34kJ/kg/d). Physical activity index,
      expressed as a multiple of basal metabolic rate (BMR), averaged 2.40 +/- 0.41
      (DLW) or 2.40 +/- 0.28 (HR). CONCLUSIONS: These findings suggest an extremely
      high level of physical activity in Gambian men during intense agricultural work
      (wet season). This contrasts with the relative food shortage, previously reported
      during the harvesting period. We conclude that the assessment of EE during the
      agricultural season in non-industrialized countries needs further investigations
      in order to obtain information on the energy requirement of these populations.
      For this purpose the use of the DLW and HR methods have been shown to be useful
      and complementary.

PMID- 8735309
TI  - Computed tomography visceral adipose tissue volume measurements of Italians.
      Predictive equations.
AB  - OBJECTIVES: To evaluate total visceral adipose tissue (AT) volumes in relation to
      single slices of visceral AT area measured at different levels and to other
      simple anthropometric measurements. DESIGN: Only outpatients examined in a
      metabolic unit were considered; subjects without conditions known to affect AT
      distribution who gave their informed consent were recruited. SETTING: All
      subjects were hospitalized in the Department of Internal Medicine of the
      University of Messina. SUBJECTS: 90 adult subjects of which 18 men and 42 pre-
      and 30 post-menopausal women. Ages ranged from 18 to 69 years and body mass
      indexes ranged from 22 to 50. INTERVENTIONS: The AT volume was calculated by
      computed tomography from the AT area of five scans and from the distances between
      these scans. RESULTS: AT area at the level of the 2nd-3rd lumbar vertebra had by
      itself the highest predictive power in men (s.e. = 6.8%), in post-menopausal
      women (s.e. = 7.4%) and, together with age, in pre-menopausal women (s.e. = 14%).
      Of the non-radiological parameters it was waist circumference, together with age,
      which showed the highest predictive power in men (s.e. = 21%), pre-menopausal
      women (s.e. = 25%) and, together with height, in post-menopausal women (s.e. =
      33%). CONCLUSIONS: A single scan measurement at the lumbar level was confirmed to
      be representative of total visceral AT volume. Waist circumference was the non
      radiological parameter that best correlated with volume.

PMID- 8735310
TI  - Measurement of body composition in chronic renal failure: comparison of skinfold
      anthropometry and bioelectrical impedance with dual energy X-ray absorptiometry.
AB  - OBJECTIVE: To compare the validity of skinfold anthropometry (SFA) and
      bioelectrical impedance (BIA) for the measurement of body composition in patients
      with chronic renal failure (CRF). DESIGN: We compared measurement of % total body
      fat (%TBF) and fat-free mass (FFM) by BIA and SFA, with dual energy X-ray
      absorptiometry (DEXA) as the criterion method to determine their value in groups
      of patients with CRF and a group of normal controls. SETTING: Renal Unit, Leeds
      General Infirmary and Centre for Bone and Body Composition Research, University
      of Leeds, UK. RESULTS: 95% levels of agreement of BIA and SFA with DEXA (using
      the method of Bland & Altman) showed considerable variation, which was greater
      for both techniques in CRF patients than in a normal control group. In normal
      subjects, BIA derived values for % TBF and FFM showed a closer agreement with
      DEXA than did SFA (% TBF BIA-DEXA -8.2 to +3.8%; %TBF SFA-DEXA -4.6 to +12.1%;
      FFM BIA-DEXA -2.5 to +5.8kg; FFM SFA-DEXA -7.9 to +3.8 kg). However, in CRF
      patients no differences in the 95% levels of agreement were observed for % TBF or
      FFM derived from BIA or SFA compared with DEXA (%TBF BIA-DEXA -13.7 to +8.3%;
      %TBF SFA-DEXA -13.0 to +9.4%; FFM BIA-DEXA -5.1 to +9.6 kg; FFM SFA-DEXA -5.6 to
      +9.1 kg). CONCLUSIONS: In CRF, errors of both BIA and SFA in comparison with DEXA
      are greater than in normal subjects. The magnitude of the limits of intermethod
      difference are relatively much greater for measurement of % TBF than FFM for both
      BIA and SFA in CRF patients and control subjects.

PMID- 8735311
TI  - Evaluation of a food frequency questionnaire used to assess nutrient intakes in
      pregnant women.
AB  - OBJECTIVE: To compare nutrient intakes assessed by food frequency questionnaire
      (FFQ) with those determined from food diaries. DESIGN: A 100-item FFQ was
      administered to women at 15 weeks of pregnancy. Food diaries were kept for a 4
      day period at 16 weeks of pregnancy. SETTING: Community-based study of a general
      population sample of pregnant women booked for delivery at the Princess Anne
      Maternity Hospital, Southampton, UK. SUBJECTS: 603 women were recruited. Complete
      dietary data were provided by 569 women. RESULTS: Nutrient intakes determined by
      FFQ were greater than those from food diaries. Spearman rank correlation
      coefficients for macronutrients ranged from 0.27 (protein and starch) to 0.37
      (fat). Stronger correlations for energy, fat and carbohydrate were seen in women
      who did not experience nausea, suggesting that the level of agreement observed
      between the FFQ and food diary in the whole group may be an underestimate of the
      true agreement. The percentage of individuals classified to the same quarter of
      the distribution of nutrient intake by the FFQ and diaries ranged from 30%
      (starch) to 41% (calcium), with between 4% (riboflavin) and 8% (energy, protein
      and vitamin E) classified to the opposite quarters. Using serum vitamin C as an
      independent biomarker of intake, the percentage of individuals classified to the
      correct quarter of intake was similar for the FFQ and diary (34% and 37%), with
      8% (FFQ) and 6% (diary) misclassified to the opposite quarter. CONCLUSION: The
      FFQ appears to give meaningful estimates of nutrient intake in early pregnancy
      which can be used to rank individuals within the distribution.

PMID- 8735313
TI  - Vitamin D deficiency in veiled Kuwaiti women.
AB  - OBJECTIVE: To study vitamin D deficiency in veiled Kuwaiti women. DESIGN:
      Prospective on cases and volunteers. SETTING: The medical department in a general
      hospital in Kuwait serving about 300000 persons (Adan Hospital). SUBJECTS: The
      authors saw four cases of unexplained vitamin D deficiency osteomalacia in
      otherwise healthy veiled Kuwaiti women. This stimulated us to study 50 veiled
      volunteer Kuwaiti women aged between 14 and 45 years old who had three children
      or less, and 22 unveiled volunteer Kuwaiti women with matched age and number of
      children as control. INTERVENTIONS: Blood samples were taken to check levels of
      25-hydroxy cholecalciferol, calcium, phosphorus and alkaline phosphatase. Blood
      urea, serum creatinine, serum bilirubin, serum alanine transaminase, serum
      aspartate transaminase, serum lactic dehydroginase, prothrombin time, urine for
      proteins and pH were checked to exclude renal and hepatic disease. RESULTS:
      showed subclinical vitamin D deficiency among veiled women and two cases of
      clinically overt osteomalacia were discovered among the veiled volunteers
      suggesting a high prevalence of the disease among veiled Kuwaiti women.

PMID- 8735312
TI  - Association between nutritional status, cell-mediated immune status and acute
      lower respiratory infections in Bangladeshi children.
AB  - OBJECTIVE: To investigate the association between nutritional status, cell
      mediated immune status and the incidence of acute lower respiratory infections
      (ALRI). DESIGN: Community-based longitudinal study. SETTING: Three villages in
      rural Bangladesh at Matlab. SUBJECT: 696 children aged 0-59 months were followed
      up for a year. METHODS: Trained field workers visited all children every fourth
      day and collected morbidity data for the preceding three days by recall. To
      determine the type and severity of respiratory infections, the field workers
      physically examined each child reporting a cough. Anthropometric status was
      determined monthly and cell-mediated immune status by skin tests was assessed at
      the beginning of the study and thereafter every 3 months. RESULTS: The incidence
      of ALRI was 23 episodes per 100 child-years. A total of 73-78% of the children
      were below -2 z score weight for age, 15-30% were below - 2 z score weight for
      height, and 68-76% were below -2 z score height for age. In logistic regression
      models, malnutrition as assessed by weight-for-height status [odds ratio (OR)
      0.66, 95% confidence interval (CI) 0.45-0.96, P = 0.03] or weight-for-age status
      (OR 0.64, 95% CI 0.45-0.92, P = 0.02) was significant predictor of ALRI. Anergic
      children had a higher risk of ALRI which approached to be statistically
      significant (OR 1.81, 95% CI 0.92-3.55, P = 0.08). CONCLUSIONS: Improvement of
      nutritional and cell-mediated immune status in rural Bangladeshi children should
      reduce the incidence of ALRI.

PMID- 8735314
TI  - Basal metabolic rate of women on the contraceptive pill.
AB  - OBJECTIVE: To investigate the variability in basal metabolic rate (BMR) of women
      taking the contraceptive pill, through sequential measurement over the course of
      one menstrual cycle. DESIGN: Randomised. SETTING: Metabolic room, School of
      Biological and Molecular Sciences, Oxford Brookes University. SUBJECTS AND
      MEASUREMENTS: BMR of five weight-stable women taking the contraceptive pill, was
      measured three to four times each week for a period of five consecutive weeks,
      BMR was measured using a Douglas bag. RESULTS: The pattern of variation in BMR
      was random for individual subjects throughout the period of measurement. The
      level of intraindividual variation indicated by the coefficient of variation (CV)
      ranged from 2.4 to 4.87%. CONCLUSIONS: Women taking the contraceptive pill did
      not exhibit the cyclicity or variation in BMR observed in some normally ovulating
      subjects. BMR in women taking the contraceptive pill could therefore be
      considered a 'biological constant'.

PMID- 8735315
TI  - The 'Green Keyhole' nutritional campaign in Sweden: do women with more knowledge
      have better dietary practices?
AB  - INTRODUCTION: In 1989 the National Food Administration in Sweden introduced a
      food-marking symbol called the 'Green Keyhole'. The aim of the campaign is to
      help consumers make lowfat, high-fibre food choices. OBJECTIVE: To describe the
      knowledge of the Green Keyhole symbol in a general female population, and to
      examine whether knowledge is associated with reported intake of dietary fat and
      fibre. SUBJECTS: 616 randomly selected women were examined and interviewed.
      METHODS: Intakes of dietary fat and fibre were analysed in relation to knowledge
      of the Green Keyhole symbol. Knowledge was assessed by means of an open-ended
      question. RESULTS: 62% of the women adequately understood the meaning of the
      Green Keyhole. These women were significantly younger (P < 0.0001). Mean body
      mass index (kg/m2+/-s.e.m.) was significantly higher among the women with more
      knowledge of the Green Keyhole symbol than those with less knowledge: 26.4 +/-
      0.2 vs 25.6 +/- 0.2, (P = 0.002). There were no major differences in total fat
      intake or total fibre intake between the women with less and more knowledge.
      However the ratios of polyunsaturated fatty acids to saturated fatty acids and
      fibre intake per 4200 kJ (1000 kcal) were higher (P = 0.05 and P = 0.03,
      respectively) and intake of saturated fatty acids was lower (P = 0.05) in the
      diet among women with better knowledge. CONCLUSIONS: The female population
      described here understands the campaign but their dietary behaviours do not
      appear to conform to the low-fat message.

PMID- 8735316
TI  - Interactions of serum ferritin with traditional cardiovascular risk factors.

PMID- 8735317
TI  - Commentary: inpatient nurse manager.

PMID- 8735319
TI  - Getting back to normal: the family experience during early stage breast cancer.
AB  - PURPOSE: To describe the process of normalization as it emerged from a study of
      families coping with early stage breast cancer. DESIGN: Qualitative, grounded
      theory. SAMPLE: Fifty-five women newly diagnosed with early stage breast cancer
      and their families. Fifty-eight percent had lumpectomy, and the remainder had
      mastectomy. Some had no further treatment, but others received radiation,
      chemotherapy, or tamoxifen. Nineteen women had positive nodes. METHODS: Five
      semistructured family and couple interviews for each family from diagnosis to one
      year later. MAIN RESEARCH VARIABLES: Process of normalization, issues and
      challenges faced, and problems coping. FINDINGS: Getting back to normal, defined
      as a safe, desirable, and stable state, was important for these families.
      Strategies used to get back to normal included seeing their families as normal,
      maintaining or returning to usual patterns quickly, minimizing disruptiveness,
      deemphasizing sick role demands, reframing negatives, and putting the cancer
      behind them. Factors influencing the process were family perspective of cancer,
      visibility or disruptiveness of symptoms of and treatments for cancer, family
      flexibility, experience with illness, life stage, and congruency of views.
      CONCLUSIONS: Families who adjust more easily view changes from normal as
      temporary, are flexible, see themselves as normal given the demands of their
      situation, share similar views, experience less major disruption or intrusiveness
      from treatments and their side effects, and appropriately use strategies to get
      back to normal. IMPLICATIONS FOR PRACTICE: Study findings emphasize the
      importance of maintaining normal routines as much as possible and getting back to
      normal quickly. Nurses must accurately assess family coping to identify those
      having difficulty and those at risk for difficulty. Nurses can support families'
      efforts to be normal and get back to normal by providing information about what
      is generally expected and what resources are available that might be helpful.
      Nurses need to be accessible to provide counseling and/or refer as needed.

PMID- 8735320
TI  - Glial neoplasms: classification, treatment, and pathways for the future.
AB  - PURPOSE/OBJECTIVES: To provide a review of glial neoplasms including histologic
      classification, signs and symptoms, diagnostic evaluation, treatment options, and
      nursing care. DATA SOURCES: Articles, books, proceedings of national meetings.
      DATA SYNTHESIS: Glial neoplasms vary according to prognosis and treatment options
      based on histologic classifications. Prediction of deficits and potential
      complications of disease and treatment can prepare the patient and healthcare
      provider in management. Treatment options include surgery, radiation therapy, and
      chemotherapy or combinations of these options. New treatment regimes currently
      are being investigated. CONCLUSIONS: Despite advances in the diagnosis and
      treatment of malignant gliomas, the outlook remains poor. As new combination
      treatment regimens become available, nursing care will significantly affect
      outcome and quality of life. IMPLICATIONS FOR NURSING PRACTICE: Goals of nursing
      care include prevention and education related to tumor- and treatment-related
      side effects, providing support and coordinating referrals to appropriate
      services during the disease process, and helping the patient and family cope with
      this devastating disease.

PMID- 8735321
TI  - Fostering the growth of research-based oncology nursing practice.
AB  - PURPOSE/OBJECTIVES: To describe the initial stages involved in fostering a
      research-based oncology nursing practice in a comprehensive cancer program,
      including planning the initial implementation strategies to stimulate research
      awareness and create a program of research studies in clinical oncology nursing.
      DATA SOURCES: Literature searches; published articles, abstracts, and books;
      interviews with staff nurses; departmental, committee, and task force meetings;
      nursing grand rounds and workshops. DATA SYNTHESIS: Review and use of the
      available information facilitated the design of implementation strategies that
      addressed issues identified in the literature and in clinical practice.
      CONCLUSIONS: The nursing department was able to plan, introduce, and evaluate a
      series of activities directed toward integrating research and clinical practice
      and building a series of research studies in oncology nursing. Introducing both
      goals was challenging but facilitated staff learning about research,
      participating in research-related activities, and seeing results from research
      studies relevant to their clinical practice. IMPLICATIONS FOR NURSING PRACTICE:
      Research can be introduced successfully into the clinical setting if staff are
      involved in the planning and design of research-related activities and if
      research expertise is available to foster and support their participation.

PMID- 8735322
TI  - Needle wire localization for nonpalpable breast lesions: sensations, anxiety
      levels, and informational needs.
AB  - PURPOSES: To determine the sensations that women most frequently report during
      needle wire localization (NWL) for nonpalpable breast lesions, to rate
      preprocedure anxiety, and to describe what preparation women consider desirable
      for the procedure. SETTING: Outpatient breast center in a large, not-for-profit
      hospital in a major city in Texas. DESIGN: Prospective, descriptive design.
      SAMPLE: Nonprobability sample of 56 women who were an average of 57 years old
      (range = 30-87 years). Forty-three (77%) underwent single wire localization. Nine
      (16%) of the women were subsequently diagnosed with breast cancer. METHODS:
      Subjects provided demographic information preprocedure. Postprocedure, subjects
      described and rated intensity of sensations on a 0-10 verbal, numeric rating
      scale. Preprocedure anxiety was also rated. Subjects responded to the question
      "What would you have liked to have been told before NWL to best prepare you for
      the procedure?" FINDINGS: Most frequently reported sensations were pressure,
      stinging, and pain, which averaged 6, 4, and 7, respectively, in intensity. Mean
      anxiety score was 5.3 on a scale of 10 with 10 subjects rating their anxiety as
      10. Five (9%) subjects fainted during the procedure. Subjects provided valuable
      suggestions about how to prepare patients for this procedure, such as providing
      brochures and pictures about the procedure. CONCLUSIONS: Subjects are moderately
      or highly anxious before NWL of the breast and describe a variety of sensations.
      Risk factors for fainting during this procedure and strategies to prevent
      fainting must be determined. IMPLICATIONS FOR NURSING PRACTICE: Sensory
      information should be used to prepare women for NWL. Subjects' suggestions about
      how to prepare women for the procedure can be used to develop educational and
      sensory approaches to enhance preparation for the procedure and perhaps reduce
      anxiety.

PMID- 8735323
TI  - Assistive personnel: their use in cancer care--an Oncology Nursing Society
      position paper.

PMID- 8735324
TI  - Leukocyte-reduced blood components: patient benefits and practical applications.
AB  - PURPOSE/OBJECTIVES: To review the various types of filters used for red blood
      cell and platelet transfusions and to explain the trend in the use of leukocyte
      removal filters, practical information about their use, considerations in the
      selection of a filtration method, and cost-effectiveness issues. DATA SOURCES:
      Published articles, books, and the author's experience. DATA SYNTHESIS: Leukocyte
      removal filters are used to reduce complications associated with transfused white
      blood cells that are contained in units of red blood cells and platelets. These
      complications include nonhemolytic febrile transfusion reactions (NHFTRs),
      alloimmunization and refractoriness to platelet transfusion, transfusion
      transmitted cytomegalovirus (CMV), and immunomodulation. Leukocyte removal
      filters may be used at the bedside, in a hospital blood bank, or in a blood
      collection center. Factors that affect the flow rate of these filters include the
      variations in the blood component, the equipment used, and filter priming.
      Studies on the cost-effectiveness of using leukocyte-reduced blood components
      demonstrate savings based on the reduction of NHFTRs, reduction in the number of
      blood components used, and the use of filtered blood components as the equivalent
      of CMV seronegative-screened products. CONCLUSIONS: The use of leukocyte-reduced
      blood components significantly diminishes or prevents many of the adverse
      transfusion reactions associated with donor white blood cells. Leukocyte removal
      filters are cost-effective, and filters should be selected based on their ability
      to consistently achieve low leukocyte residual levels as well as their ease of
      use. IMPLICATIONS FOR NURSING PRACTICE: Physicians may order leukocyte-reduced
      blood components for specific patients, or the components may be used because of
      an established institutional transfusion policy. Nurses often participate in
      deciding on a filtration method, primarily based on ease of use. Understanding
      the considerations in selecting a filtration method will help nurses make
      appropriate decisions to ensure quality patient care.

PMID- 8735325
TI  - Discard volumes necessary for clinically useful coagulation studies from
      heparinized Hickman catheters.
AB  - PURPOSE/OBJECTIVES: Determine the blood volume that must be wasted to obtain a
      clinically useful prothrombin time (PT), activated partial thromboplastin time
      (APTT), and fibrinogen concentration for blood drawn from a heparinized (2.5 ml
      of 100 units/ml), double-lumen venous catheter. DESIGN: Prospective,
      nonrandomized study comparing test results obtained from blood samples drawn
      through the catheters with those obtained via peripheral venipuncture. Patients
      acted as their own control. SETTING: Inpatient and outpatient units of a cancer
      research center located in a mid-Atlantic city in the United States. SAMPLE:
      Twenty double-lumen 10 Fr. Hickman catheters (Bard Access Systems, Salt Lake
      City, UT) were studied in 20 adult patients with cancer who had no history of
      coagulation disorders. METHODS: Samples were collected from the red lumen of 20
      heparinized, double-lumen Hickman catheters after 5, 10, 15, 20, and 25 ml of
      blood first were discarded. PTs, APTTs, and fibrinogen concentrations were
      measured on each sample. The results were compared with those derived from a
      simultaneously obtained peripheral blood sample. MAIN RESEARCH VARIABLES: PT,
      APTT, and fibrinogen values of blood samples after 5, 10, 15, 20, and 25 ml
      discards and PT, APTT, and fibrinogen of peripheral blood samples. FINDINGS: The
      coagulation results using peripheral blood were always within the normal range
      except for one slightly elevated APTT. After 25 ml of discard, all of the PTs and
      fibrinogen concentrations and 95% of the APTTs of catheter blood were within the
      normal range and therefore clinically useful. CONCLUSIONS: Clinically useful PTs,
      APTTs, and fibrinogen concentrations often can be derived with catheter-drawn
      blood when the objective is to confirm normal coagulation. However, because it is
      very difficult to obtain heparin-free samples through heparinized, double-lumen
      Hickman catheters, peripheral blood should be drawn for coagulation testing when
      a totally heparin-free sample is needed to make a critical clinical decision.
      IMPLICATIONS FOR NURSING PRACTICE: These findings provide important information
      for practice when nurses have to decide whether to draw coagulation tests through
      a heparinized catheter. Further research is needed with larger samples in varied
      populations (e.g., pediatrics) to study catheters made of different materials and
      of different calibers.

PMID- 8735326
TI  - Recalled side effects and self-care actions of patients receiving inpatient
      chemotherapy.
AB  - PURPOSE/OBJECTIVES: To increase knowledge of the incidence and severity of
      chemotherapy side effects, identify self-care actions and their effectiveness,
      and determine patients' acceptance of and ability to complete Nail's Self-Care
      Diary (SCD) (Nail, Jones, Greene, Schipper, & Jensen, 1991). DESIGN: Descriptive,
      retrospective. SETTING: Single medical oncology unit in an urban, tertiary care,
      private institution. SAMPLE: 59 adult patients with cancer who had received at
      least one prior cycle of chemotherapy as inpatients were asked to complete the
      study forms and agreed to participate. METHODS: Eligible and consenting patients
      completed the SCD, recalling side effects and self-care since their last
      hospitalization for chemotherapy, as well as patient demographic forms and
      evaluations of the SCD. Descriptive statistics were used in analysis. FINDINGS:
      More than 50% of the patients reported having alopecia, fatigue, nausea, taste
      changes, appetite loss, sleeping difficulties, and constipation during the
      posthospitalization period. Self-care actions were employed with variable effect.
      Taking medication was among the most effective self-care actions. The majority of
      patients found the SCD easy to complete. CONCLUSIONS: Side effects noted by
      patients in this study were similar to those of other populations. IMPLICATIONS
      FOR NURSING PRACTICE: This study adds to the literature evaluating specific self
      care actions practiced by patients. Nail's SCD was found to be useful in
      collecting data retrospectively and may serve as a basis for proactive patient
      teaching regarding side-effect management.

PMID- 8735327
TI  - Information needs, sources of information, and decisional roles in women with
      breast cancer.
AB  - PURPOSE: To describe preferred and actual roles in treatment decision making
      among women with newly diagnosed breast cancer, to describe their sources of
      information, and to identify and prioritize their information needs. DESIGN:
      Cross-sectional survey. SAMPLE: Seventy-four women recently diagnosed with breast
      cancer. SETTING: Two tertiary, outpatient oncology clinics in Winnipeg, Manitoba,
      Canada. METHODS: Three measures were completed: control preferences card sort,
      Thurstone scaling of information needs, and ranking of information sources. MAIN
      RESEARCH VARIABLES: Decisional roles, sources of information, and information
      needs. FINDINGS: More women (43%) preferred and more (57%) actually assumed a
      passive role in treatment decision making. This is particularly true of older
      women. Although 37% of women preferred a collaborative role, only 19% were able
      to assume such a role. The women preferred personal sources of information
      (physician, nurse, friend, or relative) over written sources. A medical journal
      was more relevant to women with higher levels of education. Most information
      needs included stage of disease, likelihood of cure, and treatment options. The
      women ranked self-care issues and sexuality as least important; older women,
      however, ranked self-care issues as more important. CONCLUSIONS: Women who want
      collaborative roles in decision making may experience difficulty in achieving
      such roles. Personal sources of information were more important to women than
      written sources. IMPLICATIONS FOR NURSING PRACTICE: Nurses can use a knowledge of
      women's priorities for information to guide information sharing. Nurses can
      assess women's desired roles in treatment decision making and facilitate women
      achieving their preferred roles.

PMID- 8735328
TI  - The effects of informational audiotapes on knowledge and self-care behaviors of
      patients undergoing radiation therapy.
AB  - PURPOSE/OBJECTIVES: To develop and test the effects of informational audiotapes
      on knowledge and management of side effects in subjects undergoing radiation
      therapy. DESIGN: Post-test-only control group design. SETTING: A large urban
      radiation oncology department. SAMPLE: Seventy-five adult patients (with a mean
      age of 53 years) who were receiving radiation therapy. METHODS: Subjects were
      randomized into control and experimental groups. The control group received the
      facility's standard care, while the experimental group received the standard care
      and also listened to informational audiotapes. Patients completed a demographic
      data form, a knowledge test, and the Radiation Side Effects Profile (RSEP). MAIN
      RESEARCH VARIABLES: Number and severity of side effects, self-care measures used
      to manage the side effects, and helpfulness of these measures. FINDINGS: Patients
      in the experimental group were more knowledgeable about radiation therapy and its
      side effects, used more self-care measures, and practiced more helpful self-care
      behaviors than control group subjects. CONCLUSIONS: Audiotapes are an effective
      strategy for teaching self-care practices to patients undergoing radiation
      therapy. IMPLICATIONS FOR NURSING PRACTICE: An important role of the nurse is to
      assess clients for side effects of treatment and provide the knowledge necessary
      for patients to become active participants in their care. Use of audiotapes
      ensured that patients received the information they needed at times and places
      that were convenient to them.

PMID- 8735329
TI  - Certification of oncology nurses: a history.

PMID- 8735330
TI  - School of nursing responds to changes in health care.

PMID- 8735331
TI  - Rural nurses keep up with the trends.

PMID- 8735332
TI  - Changing prescriptive authority of advanced practice nurses.

PMID- 8735333
TI  - Maintaining flexibility in changing times.

PMID- 8735334
TI  - "8 in 1".

PMID- 8735335
TI  - Transient acute monoblastic leukemia with reciprocal (8;16)(p11;p13)
      translocation.

PMID- 8735336
TI  - Prognostic variables and survival in pediatric acute lymphoblastic leukemias:
      cancer institute experience.
AB  - This presentation is an analysis of front-end prognostic variables in achieving a
      complete response, a continuous complete remission, and disease-free survival in
      pediatric acute lymphoblastic leukemia at the Cancer Institute, Madras, India
      between 1983 and 1988. The clinical characteristics at presentation showed that
      virtually 100% of patients belong to the poor risk category, age < 3 years of > 6
      years 72.2%, WBC > 10,000/mm3 59.8%, blast count > 50% 39.2%, organomegaly 91.8%,
      and L2 morphology 66.0%. All patients had more than one risk factor. Between 1983
      and 1988, 97 children were treated on a pilot protocol designed in collaboration
      with the Lymphoma Biology Division of the Pediatric Oncology Branch of the
      National Cancer Institute, Bethesda, Maryland. The protocol was designed for a
      poor prognostic group. The significance of implicated poor prognostic factors was
      analyzed using the Cox proportional hazard model. Age at presentation was the
      only variable that emerged as an independent risk factor, and sex appeared to be
      a modifier. No other variables attained significance. Survival data were
      calculated by the Kaplan-Meier method. The relapse-free and event-free survivals
      up to 10 years were 50.7% and 38.1%, and compare reasonably well with results
      reported for similar groups elsewhere for the same period.

PMID- 8735337
TI  - Infection risk factors in febrile, neutropenic children and adolescents.
AB  - We studied 276 fever episodes with an absolute neutrophil count (ANC) < 500/mm3
      to determine patient characteristics predicting serious infection. Infections
      occurred in 38% of patients. Blood cultures were positive in 58% of documented
      infections. There was no difference in the rates of infection or positive blood
      culture when ANC was < 200/mm3 compared with a higher ANC. However, certain high
      risk infections were more common with an ANC < 200/ mm3. Leukemia patients had
      more infections compared with other groups. Serious infections were more common
      during induction therapy or relapse. Infection incidence varied significantly
      with patient age and onset of fever in the inpatients. Less than one fifth of
      febrile neutropenic episodes had no risk features for serious infection. We
      conclude that several clinical characteristics correlate with serious infection
      in febrile, neutropenic children and adolescents receiving modern supportive
      care. Despite improvements in supportive care measures, most febrile, neutropenic
      patients need close observation and empiric intravenous antibiotic therapy.

PMID- 8735338
TI  - Varicella zoster infections in children with acute lymphoblastic leukemia.
AB  - During the period July 1986 through December 1991, 67 children were treated for
      non-B-cell acute lymphoblastic leukemia at The Juliane Marie Centre, GGK, The
      University Hospital Rigshospitalet, Copenhagen. Twenty-five children were
      susceptible to varicella zoster (VZ) virus at diagnosis. For these patients the
      cumulated risk of VZ exposure was 90% after 32 months. Five patients developed
      varicella (two of whom had pneumonitis) during the period of antileukemic
      treatment. Two of these had received prophylactic treatment with acyclovir. The 2
      year cumulated risk of having chickenpox or herpes zoster in children with
      previous VZ infection was 24% and 34%, respectively. VZ vaccination ought to be
      considered for this group of children in order to diminish transmission and
      morbidity.

PMID- 8735339
TI  - Assessment of neutrophil chemotaxis and random migration in children with
      thalassemia major.
AB  - Neutrophil chemotaxis and random migration were evaluated in 21 patients with
      thalassemia major and 21 healthy controls by a filter technique (Boyden chamber).
      Chemotactic and random migrations in patient group were found to be defective,
      which may partially account for the increased susceptibility to infection
      occasionally observed in these patients. The effects of serum ferritin levels,
      transferrin saturations that show iron overload, total count of blood
      transfusions for chronic immunostimulation, desferrioxamine therapy, and
      splenectomy on these neutrophil functions were examined in thalassemic patients
      in order to determine whether they are responsible for these defective functions
      because the mechanism of abnormal neutrophil chemotaxis and random mobility in
      thalassemic patients is not still clear.

PMID- 8735340
TI  - Ondansetron in radiation therapy of brain tumor in children.
AB  - Ten children receiving 5 to 6 week courses of radiotherapy after brain tumor
      surgery were given ondansetron treatment for persistent nausea and emesis. All
      patients continued the ondansetron treatment until the end of their radiotherapy
      course. Nausea, emesis, appetite, and adverse events were scored throughout the
      ondansetron treatment period. Ondansetron was well tolerated by all patients and
      was effective at reducing symptoms in 60% of the children.

PMID- 8735341
TI  - Loss of heterozygosity in the VNTR region of intron 1 of P53 in two
      retinoblastoma cases.
AB  - Loss of heterozygosity (LOH) was studied in 10 primary retinoblastoma tumors in
      the VNTR region of intron 1 in p53 gene by the polymerase chain reaction. To our
      knowledge mutations have not been reported in the p53 gene in retinoblastoma
      primary tumors. Heterozygosity was found at this region in 5 of 10 cases. Two
      pathology paraffin block samples showed loss of heterozygosity.

PMID- 8735342
TI  - Detection of minimal residual disease in childhood acute lymphoblastic leukemia
      after termination of therapy.
AB  - Using IgH and TCR gamma gene rearrangements as gene markers, we detected minimal
      residual disease (MRD) by means of the polymerase chain reaction (PCR) and
      restriction analysis. Of 18 children with acute lymphoblastic leukemia (ALL),
      MRDs were detected in 9 patients after termination of therapy. All 18 patients
      had been followed for 1.5 to 102 months after detection. Three of the nine MRD
      positive patients relapsed within 3 to 6 months; none of the nine MRD-negative
      patients relapsed. We suggest that MRD negativity at the end of therapy might be
      an important factor for long-term disease-free survival, because the negative
      cases had a very low risk of relapse. Because the outcome for MRD-positive cases
      is more difficult to evaluate, patients with MRD after termination of therapy
      should be monitored.

PMID- 8735343
TI  - Plesiomonas shigelloides septicemia: case report and literature review.
AB  - A 13-year-old girl with Plesiomonas shigelloides septicemia is reported. The
      infection occurred while she was receiving an allogeneic bone marrow
      transplantation for acute promyelocytic leukemia. Treatment with ciprofloxacin
      was successful. Twenty-one cases of Plesiomonas septicemia have been reported in
      the literature. Immunocompromised hosts, especially neonates, are commonly
      affected. The case mortality rate is high, with 13 of the reported patients dying
      of the infection. Successful treatment relies on the early identification of the
      organism and implementation of effective antibiotics.

PMID- 8735345
TI  - Breast metastasis in adolescents with alveolar rhabdomyosarcoma of the
      extremities: report of two cases.
AB  - We describe two adolescent girls with alveolar rhabdomyosarcoma arising from
      extremities who developed bilateral breast metastasis in their clinical course.
      In both cases, there was widespread systemic disease at initial presentation.
      Although complete remission was achieved on the 25th week post-chemotherapy
      initiation, the first patient developed breast metastasis in addition to systemic
      recurrence on the 44th week and expired. For the second patient, breast
      metastasis was noted in addition to systemic disease at initial presentation.
      Aggressive chemotherapy with autologous transplant and radiotherapy were given in
      addition to bilateral subcutaneous total mastectomy. The patient remained in
      complete remission 3 months post-therapy. We postulate that adolescent females
      with alveolar rhabdomyosarcoma of the extremities have a high risk of developing
      breast metastasis in the pubertal period, and aggressive multidisciplinary
      treatment is indicated.

PMID- 8735344
TI  - Hematological studies in children with Down syndrome.
AB  - Previous studies have reported erythrocyte macrocytosis in adults and children
      with Down syndrome (DS), the significance of which remains unclear. We compared
      hematological parameters of 50 DS children aged 2 to 15 years, divided into three
      age groups, with those of 68 aged-matched healthy children. Patients with DS had
      a significantly increased mean corpuscular volume (MCV) and hemoglobin in all
      groups when compared with the controls. Erythrocyte creatine content, hexokinase
      (Hk) activity, erythrocyte and serum folates, vitamin B12, haptoglobin, serum
      iron, and ferritin were tested. All of these parameters were not significantly
      different from those of the control group. We conclude that macrocytosis may not
      be an expression of reduced red cell survival but rather of an altered folate
      remethylation pathway, secondary to enhanced cystathionine beta-synthase (CBS)
      activity, the gene for which is present on chromosome 21.

PMID- 8735346
TI  - Superior sagittal sinus thrombosis complicating maintenance treatment for acute
      lymphoblastic leukemia.
AB  - A girl with acute lymphoblastic leukemia in remission had two seizures during the
      maintenance phase of her treatment. Magnetic resonance imaging with angiography
      identified a superior sagittal sinus thrombosis as the likely explanation for her
      symptoms. Possible causes are considered, and previous reports of the
      neurotoxicity of agents used in the treatment of leukemia are reviewed.

PMID- 8735347
TI  - Masked Hodgkin's disease: the pruriginous disguise.

PMID- 8735348
TI  - Combined administration of hepatitis B vaccine and hepatitis B immune globulin in
      children with cancer.

PMID- 8735349
TI  - Research on the menopause.

PMID- 8735350
TI  - The demography of menopause.
AB  - Menopause marks a time of dramatic hormonal and often social change for women.
      Both risk factors and health needs are likely to change as women pass through
      menopause. This paper examines the demographic characteristics of the world
      population of menopausal and post-menopausal women, and also examines the
      implication of menopause for mortality risks. The numbers of women involved are
      large. Using age 50 as a proxy for menopause, about 25 million women pass through
      menopause each year, and we estimate that in 1990 there were 467 million post
      menopausal women in the world, with an average age of about 60 years. By 2030,
      the world population of menopausal and postmenopausal women is projected to
      increase to 1.2 billion, with 47 million new entrants each year. The mortality
      implications of menopause are also substantial. Ratios of female to male
      mortality risks from all causes and from all major cause groups except neoplasms
      decline to low levels around menopause or shortly thereafter, and then rise again
      to near unity. This pattern is taken as evidence that the female reproductive
      period is broadly protective of health, but that this protection disappears after
      menopause. The main protective effect is through reduced risk of cardiovascular
      disease mortality, partially offset by increased risks of cancer mortality,
      particularly of the breast and endometrium.

PMID- 8735351
TI  - The endocrinology of the menopause.
AB  - Changes in the endocrinology of the pituitary-ovarian axis first become manifest
      at about the age of 40, a selective rise in serum follicle stimulating hormone
      (FSH) levels occurring at about the same time as a marked acceleration in the
      loss of primordial follicles from the ovary. FSH levels gradually increase with
      increasing age in women who continue to cycle regularly. During the menopausal
      transition, initiated when changes in cycle frequency or in menstrual flow are
      first observed, both gonadotrophins, oestradiol and inhibin show a marked degree
      of variability with abrupt changes from typical post-menopausal patterns to those
      characteristic of the reproductive age group. Within 1-2 years after the final
      menstrual period or menopause, FSH levels are markedly elevated, luteinizing
      hormone (LH) levels moderately so, while oestradiol and inhibin levels are low or
      undetectable. Post-menopausally, adrenal androstenedione is the major source of
      oestrogen and serum testosterone levels fall moderately, with oophorectomy
      leading to a further significant fall. Serum sex hormone binding globulin levels
      fall to a small degree post-menopausally. Areas of persisting controversy include
      the question of whether oestradiol levels fall with increasing age prior to the
      onset of the menopausal transition, the relative roles of oestradiol and inhibin
      in the selective rise of serum FSH and the role of serum androgens post
      menopausally.

PMID- 8735352
TI  - The normal menopause transition: an overview.
AB  - OBJECTIVES: This review emphasizes results from population based studies in order
      to provide a reliable knowledge base and define major knowledge gaps for future
      research. METHODS: The review systematically addresses the following aspects of
      menopause research: definition of menopause and menopause transitions; age at
      natural menopause and at inception of perimenopause; factors affecting timing and
      length of menopause transitions; concurrent hormone, menstrual and vascular
      changes. Under each substantive heading, available reports of original research
      are reviewed, assessed for reliability and summarized with respect to their
      contribution to the knowledge base. RESULTS: From this review, the following
      reliable information can be summarized: median age at natural menopause in
      Caucasian women occurs between 50 and 51-55 years of age, is not affected by
      timing of surgical menopause and is affected by cigarette smoking, with current
      smokers having an earlier menopause by 1.5-2.0 years. No other factors appear to
      have an independent effect on age at menopause. There is no evidence of any
      secular trend in age at menopause. Evidence is accumulating that most
      physiological change associated with menopause either occurs or begins before the
      final menstrual period. CONCLUSIONS: We lack reliable information on the
      following: estimates of age at menopause from non-industrialized countries and
      diverse ethnic groups; information on perimenopause; differing perceptions of
      menopause, cross culturally; multi-disciplinary prospective data that can link
      various processes into coherent patterns.

PMID- 8735353
TI  - Well-being, symptoms and the menopausal transition.
AB  - OBJECTIVES: This paper reviews the knowledge accumulated from published
      population studies of health and ill-health experiences during the menopausal
      transition. RESULTS: Well-being: mid-aged women are more likely to report
      positive moods than negative moods. Well-being is not associated with menopausal
      status but is associated with current health status, psychosocial and lifestyle
      variables. SYMPTOMS: SYMPTOMS vary greatly across cultures, with North American
      and European samples reporting higher rates of symptoms than Asian women. The
      most symptomatic women in the North American samples and Australian studies are
      those whose menstrual cycles have changed. Vasomotor symptoms increase through
      the menopausal transition. Other variables such as socio-demographic, health
      status, stress, premenstrual complaints, attitudes to ageing and menopause, and
      health behaviors are associated with the occurrence of symptoms. Psychological
      complaints: There is no increase in the incidence of major depression with the
      menopause. Negative moods are not associated with the natural menopausal
      transition. Factors associated with negative moods include surgical menopause,
      prior depression, health status, menstrual problems, social and family stressors
      and negative attitudes to menopause. Sexuality: Several studies suggest a decline
      in sexual functioning associated with menopausal status rather than ageing.
      Social factors and health status factors are also associated with sexual
      outcomes. RECOMMENDATIONS: Future research should bring together biomedical and
      sociological aspects. Positive aspects of health should be assessed as well as
      troubling symptoms. Longitudinal studies are needed with measures of hormonal
      change. Promoting positive attitudes to ageing and menopause, health lifestyles
      and stress reduction can be used as community interventions and as part of
      individual care.

PMID- 8735354
TI  - Hormonal and non-hormonal interventions for menopausal symptoms.
AB  - Recent cohort studies confirm that only flushes, night sweats and vaginal dryness
      are provenly associated with ovarian failure. Experiments nave demonstrated that
      these symptoms and insomnia associated with nocturnal vasomotor symptoms are more
      effectively controlled by oestrogen than placebo. Hormonal interventions include
      a variety of oestrogen or oestrogen/progestogen regimes. Non-hormonal treatments
      of flushes include exercise, paced respiration and psychotherapy. After the
      menopause vaginal atrophy and some urinary symptoms respond to local oestrogen
      and vaginal dryness in also prevented by lubricants. Libido is not increased by
      oestrogen therapy but may be improved by testosterone. Depression is common in
      middle-aged women but is not specifically associated with the hormonal changes
      occurring at the menopause. Oestrogen therapy may improve and stabilise mood
      during the peri-menopause but there is no firm evidence that it is effective for
      depression after the menopause. Arthralgia is not a symptom specific to menopause
      and experimental evidence concerning the role of oestrogen in the treatment of
      rheumatoid arthritis is inconclusive. Cognitive function is not related to
      menopause and measures such as stopping smoking, exercise and maintaining body
      weight may be partly effective in preventing menopausal symptoms.

PMID- 8735355
TI  - The social and cultural context of menopause.

PMID- 8735356
TI  - The perimenopause and contraception.
AB  - OBJECTIVES: To review the implications of pregnancy in women in their forties and
      the contraceptive options open to them. METHOD: Medline and popline reviews of
      the literature. RESULTS: Women in their forties are still potentially fertile,
      and pregnancy in this age group is attended with increased maternal mortality,
      spontaneous abortion, fetal anomalies and perinatal mortality. In developing
      countries, these risks are compounded by high parity and poor medical care.
      Contraception for women in this age group has special risks and benefits, both
      should be balanced to choose between the different options available. Recent
      epidemiological and clinical pharmacology studies have indicated the safety of
      extending the use of combined oral contraceptives (COCs) beyond the age of 35
      years and up to menopause. The improved picture of COCs has largely resulted from
      the use of low-dose-formulations, and avoidance of their use in women with risk
      factors for developing cardiovascular diseases. Besides their high reliability,
      which is desirable at this age, COCs will prevent the occurrence of climacteric
      symptoms and menstrual irregularities which are frequently complained of in the
      premenopausal years. Moreover, the use of COCs has a substantial protective
      effect against ovarian and endometrial cancers. Women who have reasons for
      avoiding COCs can use progestogen-only contraceptives like pills, depot
      injectables and implants. Norplant combines high efficacy and the long-term
      effect. Both copper-releasing and levonorgestrel-releasing IUDs (LNG-IUD) combine
      the advantages of high efficacy and long term effect. The reduced fecundity above
      the age of forty can allow extending the use beyond the accepted term, and up to
      one or two years beyond the menopause without the need for replacement. The
      levonorgestrel IUD has the advantage of reducing the amount of menstrual
      bleeding. The extent of use of barrier methods will depend upon the availability
      of a back-up by abortion service in case of failure. The condom has the added
      benefit of protection against STDs. Male or female sterilization is an excellent
      contraceptive option, provided that this approach is culturally acceptable and
      available at reasonable cost and low risk. CONCLUSION: Increasing the number of
      contraceptive options available to premenopausal women will improve proper
      counseling and enhance compliance.

PMID- 8735357
TI  - Osteoporotic fractures: background and prevention strategies.
AB  - OBJECTIVES: To review current knowledge of the epidemiology, pathogenesis,
      prevention and treatment of osteoporosis, with particular reference to issues
      related to the menopause. METHODS: Peer-reviewed publications were assessed.
      RESULTS: Much international variation exists in the prevalence of osteoporosis
      and the incidence of fracture. Risk fractures for osteoporosis are numerous. The
      menopause and other causes of hypogonadism in both women and men strongly
      predispose to osteoporosis. Various endocrinopathies, especially glucocorticoid
      excess, also are important. The contribution of family history may be explained
      by one or more genetic markers. Poor vitamin D and calcium nutrition, smoking,
      high alcohol consumption and inactivity increase risk. Reduced bone mass is a
      major risk factor for fracture, although the magnitude of that risk may vary
      between populations. In addition, bone fragility, length of the femoral neck (for
      hip fracture), history of prior fracture (for vertebral fracture) and falls
      affect fracture risk. Useful methods for measuring bone density are available for
      both epidemiologic surveillance and for clinical practice. Dual energy x-ray
      absorptiometry is the most desirable method in clinical care settings. Some risk
      factors can be modified for prevention of osteoporosis. Postmenopausal bone loss
      can be inhibited with estrogen or estrogen plus progestin therapy. Bone loss in
      the elderly may be moderated with calcium and vitamin D supplementation.
      Maintenance of muscle tone and strength through exercise may reduce falls.
      CONCLUSIONS. Osteoporosis is a large and growing health problem in many
      countries. Prevention of osteoporosis is a high priority, especially because
      treatment of the established disease remains sub-optimal. Prevention requires
      immediate, intermediate-term and long-term strategies. First line therapy for
      established osteoporosis in women in many countries is estrogen or estrogen plus
      progestin, calcium and vitamin D. Prospects for improved prevention of
      osteoporotic fractures are encouraging.

PMID- 8735358
TI  - The menopause and hormone replacement therapy: lipids, lipoproteins, coagulation
      and fibrinolytic factors.
AB  - OBJECTIVES: To review the recent literature concerning the effects of the
      menopause and hormone replacement therapy (HRT) on the plasma lipoprotein and
      hemostatic system, as well as on the interaction between these two coronary heart
      disease (CHD) risk factor systems. METHODS. Collection of information from
      relevant scientific journals, and by the use of Medline and Current Contents.
      RESULTS: The mainly beneficial effects of unopposed oral estrogen replacement on
      the plasma lipoprotein pattern are preserved to different degrees after addition
      of progestin to the regimen. Nortestostorone-derived progestins tend to lower HDL
      cholesterol levels more than progesterone derivatives. The slight triglyceride
      elevating effect on conjugated equine estrogens was in a large study not
      significantly counteracted by progesterone derivatives but can, according to
      other studies, be reversed by nortestosterone-derived progestins. A limited
      number of studies on transdermal administration of estradiol has suggested that
      the effects on plasma lipoproteins are smaller than during oral administration.
      There is no convincing evidence that currently used HRT regimens would
      significantly increase the risk of thrombosis. Nevertheless, the finding in some
      studies that plasma triglyceride elevations could in theory be associated with
      impaired fibrinolysis and enhanced coagulation merit further attention as some
      HRT regimens tend to increase plasma triglyceride levels. From a theoretical
      point of view, transdermal estrogen delivery would be preferable in women at risk
      for thrombosis, as they have less pronounced effects on liver functions,
      including production of hemostatic factors and very-low-density lipoprotein
      triglycerides. CONCLUSIONS: While the numerous existing HRT regimens provide many
      alternative and useful possibilities, further studies are needed concerning (a)
      novel progestins with minimal HDL cholesterol lowering effects, (b) transdermal
      and other non-oral routes for HRT, (c) possible antioxidative properties of
      estrogen and (d) metabolic links between the lipoprotein and hemostatic risk
      factor systems.

PMID- 8735359
TI  - Vascular aspects of oestrogen.

PMID- 8735360
TI  - The menopause, hormone replacement, and cardiovascular disease: the epidemiologic
      evidence.

PMID- 8735361
TI  - Postmenopausal estrogens and progestogens and the incidence of gynecologic
      cancer.
AB  - We reviewed the published medical literature to assess the impact of the use of
      estrogens, with and without progestogens, on the incidence of gynecologic cancer
      in postmenopausal women. Long-term use of an estrogen preparation that is not
      accompanied by a progestogen is associated with a large increase in the risk of
      endometrial cancer, an association that almost certainly is a causal one. The
      incidence of endometrial cancer in women who receive combined estrogen
      progestogen therapy is not elevated to nearly the same degree. There are
      suggestions that, depending on the particular combined regimen, the incidence
      need not be elevated at all beyond that of a women who has never taken hormones.
      The occurrence of other forms of gynecologic cancer appear not to be associated
      with the use of unopposed estrogens, though relevant data on cervical cancer are
      sparse. The relation of ovarian, cervical and vulvar cancer to the prior use of
      combined estrogen-progestogen therapy has only begun to be evaluated.

PMID- 8735363
TI  - Hormone replacement therapy in a risk-benefit perspective.
AB  - The relative cost-effectiveness of different treatment strategies for hormone
      replacement therapy (HRT) was assessed within the framework of a computer model.
      Where data were lacking, it was necessary to make assumptions about the effects
      of HRT, particularly in relation to combined oestrogen-progestogen therapy and
      cardiovascular disease; however, sensitivity analyses were performed to assess
      the impact of changing these assumptions on the cost-effectiveness equation. It
      appears that net expenditure by the NHS will depend critically on the direct
      costs of treatment, rather than on any indirect costs incurred or saved as a
      result of side-effects. In terms of mortality, a reduction in cardiovascular
      disease risk would have greatest impact and would overshadow any small increase
      in breast cancer risk which may be associated with long-term use. If the
      cardioprotective effect of oestrogen is real, our results suggest that long-term
      prophylactic treatment of hysterectomised women would be relatively cost
      effective. Treatment of symptomatic menopausal women for any period of time
      appears to offer very good value for money. The lack of data relating to combined
      oestrogen-progestogen therapy and cardioprotection, and the major importance of
      the latter in the equation of benefits and risks, make it more difficult to draw
      conclusions about the cost-effectiveness of treating non-hysterectomised
      asymptomatic women for prophylactic reasons.

PMID- 8735362
TI  - Hormone therapy in the menopause and breast cancer risk--a review.
AB  - OBJECTIVES: To evaluate the association between use of hormones in the menopause
      and breast cancer risk. METHODS: A qualitative review of reports published
      between 1970 and 1995. RESULTS: The risk of breast cancer starts to increase
      after 5 or more years of hormone use and remains elevated while taking hormones.
      Use for 10 or more years may be associated with a 30-80% increase in risk. From 2
      to 5 years after stopping taking hormones, the risk seems to return to unity.
      There is no difference in risk between different types of oestrogens and the
      addition of progestins does not lower the risk. CONCLUSIONS: Short term use (less
      than 5 years) seems safe with respect to breast cancer risk, while longer
      durations of use may be associated with a small, but significant increase in
      risk.

PMID- 8735364
TI  - Calcium and cell cycle control in early embryos.

PMID- 8735365
TI  - The effect of 6-dimethylaminopurine (6-DMAP) on DNA synthesis in activated
      mammalian oocytes.
AB  - Mouse, sheep and bovine metaphase II oocytes were briefly preincubated in medium
      with 6-dimethylaminopurine (6-DMAP) and thereafter activated with ethanol before
      further culture in 6-DMAP supplemented medium. The presence of 6-DMAP enhances
      the efficiency of activation and the speed of pronuclear formation but has no
      effect on DNA synthesis. These results are discussed in the context of recently
      published data showing that the preincubation of condensed chromosomes with 6
      DMAP blocks DNA synthesis when nuclei become reformed.

PMID- 8735366
TI  - Calcium-dependent development of secondary cytostatic factor (2 degrees CSF) from
      Xenopus laevis oocytes and zygotes.
AB  - Fresh cytosols extracted from unfertilised eggs of Xenopus laevis contain a
      cytostatic factor (CSF) which arrests the cell cycle at metaphase when
      microinjected into cleaving blastomeres. This CSF is sensitive to Ca2+ and is
      designated primary CSF (1 degrees CSF). During storage of Ca2(+)-containing
      cytosols at 2 degrees C, a stable CSF activity appears which is designated
      secondary CSF (2 degrees CSF). In the present study, we report that 2 degrees CSF
      activity can be induced in cytosols extracted from stage VI oocytes, unfertilised
      eggs, electrically activated eggs or blastulae, in the presence of Ca2+. Both the
      intensity and the rate of 2 degrees CSF development are dependent on the
      concentration of Ca2+ ions added to the cytosol. At Ca2+ concentrations of 5-10
      mM, 2 degrees CSF activity reaches a maximum in about 7 days. Secondary CSF is
      relatively resistant to heat but loses all activity after 5 min at 70 degrees C.
      When stored at-80 degrees C, 2 degrees CSF activity remains detectable for about
      6 weeks. Cytological observations show that blastomeres arrested by
      microinjection of 2 degrees CSF developed in cytosols of unfertilised eggs,
      activated eggs or blastulae contain metaphase chromosomes embedded in a bipolar
      spindle that has no asters developed at its poles. In contrast, blastomeres
      arrested by 2 degrees CSF in cytosols of stage VI oocytes contain condensed
      chromosomes but no spindle is formed. The mechanisms of the development of 2
      degrees CSF in Ca2(+)-containing cytosols and its mode of action are discussed.

PMID- 8735367
TI  - The role of microtubules and inositol triphosphate induced Ca2+ release in the
      tyrosine phosphorylation of mitogen-activated protein kinase in extracts of
      Xenopus laevis oocytes.
AB  - Microsomal fractions of Xenopus oocytes release preloaded 45 Ca2+ when treated
      with inositol triphosphate (InsP3). The effective concentration of InsP3 required
      for half-maximal release (EC50) is 59 nM and maximal release occurs at
      approximately 2 microM InsP3. Uptake and release of 45 Ca2+ are not altered by
      the catalytic subunit of protein kinase A, dibutyrl cyclic adenosine
      monophosphate, protein kinase A peptide inhibitor or nocodazole. In contrast,
      taxol decreases the sensitivity of the microsomal fraction to InsP3, shifting the
      EC50 for InsP3-induced Ca2+ release from 59 to 259 nM. In lysates of oocytes,
      InsP3-induced Ca2+ release causes the tyrosine phosphorylation of a 42,000 (M(r)
      42k) protein identified as 42k mitogen-activated protein (MAP) kinase. InsP3
      induced tyrosine phosphorylation of MAP kinase is prevented by BAPTA and taxol,
      but not by nocodazole. Thus, microtubule polymerisation modifies InsP3-induced
      Ca2+ release, thereby inhibiting phosphorylation of MAP kinase.

PMID- 8735368
TI  - Characterisation and role of integrins during gametic interaction and egg
      activation.
AB  - It has recently been proposed that some of the processes induced by fertilisation
      in mammals may be mediated by integrins. By performing immunofluorescence
      labelling and Western blots with antibodies directed against some of the alpha
      and beta subunits of integrins, we show here the presence of some of these
      proteins in human and hamster oocytes. Among them, alpha 2 and alpha 5 were also
      present on in vitro preparations of sea urchin egg cortices. In addition,
      antibodies raised against these two proteins were the most effective at
      inhibiting attachment and fusion of human spermatozoa with hamster oocytes. We
      suggest that alpha 2 and alpha 5 integrin chains may be common mediators in
      adhesion-fusion mechanisms triggered by fertilisation. Using similar techniques,
      we show that eggs are rich in three cytoskeletal proteins known to be linked to
      the beta chain of integrins: talin, vinculin and alpha-actinin. Moreover, we
      found that talin and alpha-actinin were associated with proteins phosphorylated
      on tyrosine after fertilisation in sea urchin eggs. We suggest that integrins
      might be involved during fertilisation and trigger egg activation through
      cytoskeletal structures.

PMID- 8735369
TI  - Protein synthesis is not required for male pronuclear formation in bovine
      zygotes.
AB  - Following fertilisation, the sperm triggers a series of intracellular changes
      which initiate oocyte activation and pronuclear formation. Oocyte activation can
      also be induced artificially by several chemicals, such as the calcium ionophore
      A23187. The sperm nucleus is transformed into the male pronucleus through the
      interaction of oocyte cytoplasmic factors. The profile of protein synthesis is
      different in bovine oocytes following fertilisation and parthenogenetic
      activation. The formation of male and female pronuclei was not blocked by the
      presence of the protein synthesis inhibitor cycloheximide. These results suggest
      that bovine oocyte activation by sperm and parthenogenetic activation induce
      different cytoplasmic responses for protein synthesis and that new protein
      synthesis is not required for male pronuclear formation in bovine zygotes.

PMID- 8735370
TI  - Immunocytochemical localisation of the nucleolar protein fibrillarin and RNA
      polymerase I during mouse early embryogenesis.
AB  - We have employed immunocytochemical procedures to localise the nucleolar protein
      fibrillarin and the enzyme RNA polymerase I in the numerous dense fibrillar
      bodies (nucleolar precursor bodies) which appear in the nuclei of mammalian early
      embryos. The aim of this study was to search for relationships between the
      localisation of these proteins, the changes in the structure of the nucleolar
      precursor bodies and the resumption of rRNA gene transcription during mouse early
      embryogenesis. Three human autoimmune sera which recognised fibrillarin and a
      rabbit antiserum created against RNA polymerase I were employed for fluorescence
      and electron microscopic immunocytochemical assays. A statistical analysis was
      also applied. Immunocytochemistry revealed that fibrillarin and RNA polymerase I
      showed the same localisation in the nucleolar precursor bodies. These proteins
      were immunolocalised only from the late 2-cell stage onward. Fibrillarin was
      initially detected at the periphery of the nucleolar precursor bodies and the
      labelling gradually increased until the morula and blastocyst stages, where
      normally active nucleoli are found. The pattern of increase of fibrillarin during
      early embryogenesis shows a parallelism with the rise in rRNA gene transcription
      occurring during these embryonic stages, and a possible correlation between these
      two phenomena is suggested. Results demonstrated that nucleolar precursor bodies
      differ in their biochemical composition from the nucleolus and also from the
      prenucleolar bodies which appear during mitosis. When anti-fibrillarin antibodies
      were microinjected into the male pronucleus of mouse embryos to analyse the
      functions of fibrillarin during early development, they partially blocked the
      early development of mouse embryos and only 23.8% of injected embryos reach the
      blastocyst stage.

PMID- 8735371
TI  - The influence of ploidy on the distribution of cells in chimaeric mouse
      blastocysts.
AB  - Previous studies of tetraploid<-->diploid mouse chimaeras and mosaics have
      revealed that tetraploid cells do not contribute equally to all tissues of the
      conceptus. In this study we have shown that, within 30 h of aggregating cleavage
      stage embryos, tetraploid cells were non-randomly distributed among different
      tissues of the early blastocyst. They were preferentially allocated to the mural
      trophectoderm regardless of cell size at the time of aggregation. This early
      effect may underlie the restricted distribution of tetraploid cells at later
      stages. We have demonstrated for the first time that ploidy can influence the
      relative position of blastomeres in the preimplantation embryo.

PMID- 8735372
TI  - Bovine oocyte plasma membrane binding sites for sperm plasma membrane during in
      vitro oocyte maturation and fertilisation.
AB  - The experimental objective was to determine whether the capability of bovine
      oocyte plasma membrane to bind sperm changes during in vitro oocyte maturation
      and fertilisation. Binding was quantified by the intensity of
      tetramethylrhodamine isothiocyanate (TRITC) fluorescence at the periphery of
      oocytes following incubation with biotinylated sperm plasma membrane proteins and
      subsequent incubation with TRITC-avidin. Bovine oocytes were matured in vitro.
      Sample groups were removed after 0,6 and 22 h, or inseminated and further
      cultured for 24 or 48 h. Oocytes were denuded of cumulus cells and zona pellucida
      and co-incubated with 56 micrograms biotinylated bovine sperm plasma membrane
      protein for 45 min in 150 microliters drops of saline-BSA. Controls were
      incubated for the same time period in the absence of sperm plasma membrane
      proteins. All oocytes were rinsed, incubated with TRITC-avidin and subsequently
      fixed and transferred to mounting medium. Oocytes were scanned with a confocal
      microscope and analysed using ImageQuant software. The binding of sperm plasma
      membrane was quantified by integrated fluorescent intensity in standardised
      ellipses spaced around the plasma membrane of the oocyte. Values are expressed as
      mean intensity units per 320 pixel ellipse. Binding of sperm plasma membrane
      continued to increase throughout in vitro oocyte maturation and fertilisation
      (9051, 24318 and 49953 for 0 and 22 h in vitro matured oocytes and fertilised
      oocytes, respectively; p = 0.0001). A dramatic decrease in sperm plasma membrane
      binding to the oocyte plasma membrane was observed in 2-cell embryos (mean
      intensity = 24477, p = 0.0001). The observed binding was primarily due to the
      binding of sperm plasma membrane proteins, as control oocytes incubated with
      TRITC-avidin only were barely visible (integrated fluorescence intensity values
      ranged from 8 to 3757.

PMID- 8735373
TI  - First meiosis of early dictyate nuclei from primordial oocytes in mature and
      activated mouse oocytes.
AB  - Nuclei of diplotene (dictyate) primordial oocytes (PO) were transferred to
      metaphase II oocytes and to activated mouse oocytes using cell fusion techniques.
      In a metaphase II oocyte, the PO nucleus condenses within 2-3 h to bivalents
      which become arranged on the first meiotic spindle. After oocyte activation,
      homologous chromosomes segregate between the oocyte and the first polar body, and
      a diploid pronucleus-like nucleus reforms from the one set of dyads. This nucleus
      condenses in the first embryonic mitosis into 40 'somatic' chromosomes which
      coexist in the common metaphase plate with 20 somatic chromosomes originating
      from the female pronucleus. Shortening of the time between fusion and activation
      of about 1 h prevents bivalent differentiation. The PO nucleus condenses only
      partially and reforms, after oocyte activation, a pronucleus-like nucleus. This
      nucleus gives rise at the first embryonic mitosis to 20 bivalents which coexist
      with 20 somatic chromosomes originating from the female pronucleus. A PO nucleus
      introduced into an activated egg completes the first cell cycle as an intact
      interphase nucleus. It never condenses in the first embryonic mitosis into
      bivalents, and undergoes only initial condensation (preceding bivalent
      differentiation). These results indicate that: (1) condensation into bivalents,
      meiotic spindle formation and first meiotic division can be greatly accelerated
      by the introduction of an early diplotene (dictyate) oocyte nucleus into a
      metaphase II oocyte, and (2) depending on whether the diplotene nucleus enters
      the first embryonic (mitotic) cell cycle after just initiating or after
      completing the first meiosis, it gives rise at the first cleavage division to
      meiotic (bivalents) or 'somatic' chromosomes respectively.

PMID- 8735374
TI  - Child abuse treatment: a fallow land.

PMID- 8735375
TI  - The developmental outcome of children born to heroin-dependent mothers, raised at
      home or adopted.
AB  - In the present investigation we were interested to study the possible role of in
      utero exposure to heroin and of the home environmental in the etiology of long
      term developmental problems in children born to heroin-dependent parents in
      comparison to matched controls. The children were examined at .5-6 years of age
      by a developmental pediatrician and a developmental psychologist using, for the
      children up to 2.5 years of age, the Bayley Developmental Scales, and for
      children aged 3-6 years the McCarthy Scales for Children's Abilities. We examined
      83 children born to heroin-dependent mothers, and compared the results to those
      of 76 children born to heroin-dependent fathers and to three control groups; 50
      children with environmental deprivation, 50 normal children from families of
      moderate or high socioeconomic class, without environmental deprivation, and 80
      healthy children from kindergartens in Jerusalem. There were five children (6.0%)
      with significant neurological damage among the children born to heroin-dependent
      mothers and six (7.9%) children among those born to heroin-dependent fathers. The
      children born to heroin-dependent mothers had a lower birth weight and a lower
      head circumference at examination when compared to controls. The children born to
      heroin-dependent parents also had a high incidence of hyperactivity, inattention,
      and behavioral problems. The lowest DQ or IQ among the children with cognitive
      levels above 70 was found in the children with environmental deprivation, next
      was the DQ or IQ of children born to heroin-dependent fathers, then the DQ or IQ
      of the children born to heroin-dependent mothers. When the children born to
      heroin-dependent mothers were divided to those that were adopted at a very young
      age and to those raised at home, the adopted children were found to function
      similarly to the controls while those not adopted functioned significantly lower.
      Our results show that the developmental delay and behavioral disorders observed
      among children born to drug-dependent parents raised at home may primarily result
      from severe environmental deprivation and the fact that one or both parents are
      addicted. The specific role of the in-utero heroin exposure in the determination
      of the developmental outcome of these children (if they do not have significant
      neurological damage), seems to be less important in comparison to the home
      environment.

PMID- 8735376
TI  - Self-perceptions, motivation, and school functioning of low-income maltreated and
      comparison children.
AB  - Maltreated children are at risk for disturbances and delays in their
      socioemotional and scholastic functioning. This study examined the impact of
      child maltreatment and age on perceptions of competence, and the relations among
      perceived competence, motivation, and school functioning. The sample included 76
      school children living in poverty, approximately two-thirds of whom had been
      victims of child maltreatment. Results indicated that both maltreated and
      nonmaltreated children exhibited maladaptive motivational orientations toward
      scholastic tasks and poor academic performance, supporting the idea that threats
      to scholastic functioning reside as much within the ecology of poverty as in that
      of maltreatment. Over and above the general effects of poverty, maltreatment was
      found to disrupt the psychological processes accounting for children's scholastic
      performance. Results revealed that younger maltreated children (6- and 7-year
      olds) reported more inflated self-perceptions of competence and social acceptance
      than nonmaltreated children. In contrast, older maltreated children (8- through
      11-year-olds) reported lower perceived social acceptance than nonmaltreated
      children. Among older nonmaltreated children, perceived competence was positively
      related to teacher's ratings of their effort, intrinsic motivation, and grades.
      For older maltreated children, these relations among self-perceptions and school
      functioning were in the opposite direction from those of nonmaltreated children,
      suggesting that the determinants of academic engagement are different for
      maltreated and nonmaltreated children.

PMID- 8735377
TI  - A representational perspective of child abuse and prevention: internal working
      models of attachment and caregiving.
AB  - Attachment theory provides a rich theoretical framework for research and
      intervention in child abuse. This paper examines the central role of internal
      working models in the development of child-parent relationships. Mental
      representations of child attachment (in infancy and middle childhood), adult
      attachment and parental caregiving are discussed in light of the adaptational
      deficits that researchers have found to be associated with attachment insecurity.
      A reconceptualization of the link between insecurity and child abuse is
      described, highlighting disorganized attachment. Implications for child abuse
      intervention are discussed.

PMID- 8735378
TI  - The approach of Israeli health and mental health students toward child
      maltreatment.
AB  - Child maltreatment is a multidisciplinary problem with legal, medical, social
      service, public policy, and mental health components. Therefore, it is essential
      to understand how members of different disciplines approach this problem. Studies
      are lacking on this subject in Israel. A preliminary study was conducted with
      1,302 students of the four main disciplines dealing with the problem of child
      maltreatment: psychology, social work, education, and medicine. An instrument
      constructed for the purpose of this study was utilized to examine the following
      main areas used by professionals in determining cases of maltreatment: (a) their
      perception of the various situations of child maltreatment; (b) their awareness
      of the risk factors of child maltreatment; (c) their awareness of the signs of
      child maltreatment; and (d) their willingness to report various cases of
      maltreatment. The results indicate important areas in detecting cases of child
      maltreatment which students from the four disciplines may disregard. Those areas
      which could be strengthened in preparing future professionals for fulfilling
      their roles are discussed.

PMID- 8735379
TI  - The effects of a health newsletter for foster parents on their perceptions of the
      behavior and development of foster children.
AB  - Foster children have a high prevalence of medical, emotional, development, and
      behavioral problems originating both with events leading up to placement and as a
      consequence of the placement itself. Foster parents are often inadequately
      trained to understand and help with these difficulties. This may result in the
      persistence or aggravation of problems, and thereby increase the risk of
      placement failure. Because of the high demands on foster parents, any such
      training that is offered may be poorly attended. Methods to better inform these
      parents delivered in their own home may be more practical and better accepted.
      Parents at Heart is a quarterly health newsletter mailed to foster parents that
      deals with topics relevant to foster children. A questionnaire administered
      before the first issue determined some characteristics of these parents and
      ascertained their attitudes about a series of child development situations and
      behavior problems. A questionnaire after the fourth issue of Parents at Hear
      showed that many of these attitudes were influenced by the material in the
      newsletter.

PMID- 8735380
TI  - Mediators of the long-term impact of child sexual abuse: perceived stigma,
      betrayal, powerlessness, and self-blame.
AB  - Using a community sample of 192 adult women who had been sexually abused during
      childhood, the present study tested the hypothesis that perceived stigma,
      betrayal, powerlessness, and self-blame mediate the long-term effects of child
      sexual abuse. A path analysis indicated that the level of psychological distress
      currently experienced by adult women who had been sexually abused in childhood
      was mediated by feelings of stigma and self-blame. This result provides partial
      support for Finkelhor and Browne's (1985) traumagenic dynamics model of child
      sexual abuse. The limitations of the study are discussed.

PMID- 8735381
TI  - Criminal prosecution of child sexual abuse cases.
AB  - To describe the outcome of prosecuting alleged intrafamilial/caretaker child
      sexual abuse, the authors evaluated charts for 1986-1988 at La Rabida Children's
      Hospital and Research Center in Chicago, plus police records for Area V, Chicago
      for 1986-1987. The state's attorney's office provided data on outcome of legal
      proceedings. Of 451 allegations, 324 (72%) were formally designated as probable
      sexual abuse cases, and 269 (83%) alleged perpetrators were identified.
      Complaints (77 felonies, 29 misdemeanors, and 30 juvenile charges) were initiated
      by the police for preliminary hearings against 136 (51%) persons. Of the felony
      charges, 66 (85.7%) resulted in indictments, and 11 (14.3%) in dismissal of
      charges by judge or grand jury. Thirty-two (48.5%) of those indicted pleaded
      guilty, 24 (36%) went to trial; 16 (67%) were found guilty, and 8 (12%) had
      charges dismissed. Therefore, of the 77 felony complaints initiated, 48 (62%)
      ended in convictions and 29 (38%) in dismissals or not-guilty verdicts. Only 24
      (5%) of the original allegations resulted in trials. Although 30% of allegations
      and 51% of alleged perpetrators ended up in court, only 17% of the original 451
      allegations were prosecuted for a felony. For felony indictments, 36% of victims
      appeared in court. Forty-three of 48 persons found guilty served time (mean
      sentencing time, 6.8 years). The mean time from initial hearing to final
      disposition was 321 days and was significantly longer if the accused either went
      to trial (501 vs. 236 days) or was found guilty or pleaded guilty (353 vs. 254
      days for not-guilty verdicts). The authors conclude that very few children (5%)
      have to appear as witnesses in court, as most cases are resolved by plea
      bargaining, and that resolution by trial can take 12 to 16 months.

PMID- 8735382
TI  - Guide to decision-making in child abuse cases.

PMID- 8735383
TI  - Stacked generalization and simulated evolution.
AB  - A stacked generalization strategy in which an evolutionary algorithm generates
      baselevel predictive models is described. The evolutionary algorithm incorporates
      model validation and an inductive ranking criterion which encourages diversity of
      prediction errors. Higher levels of the stack of generalizers yield predictors
      that work through memory-based correction and combination of predictions produced
      by populations of models obtained in lower levels of the stack. The strategy has
      been applied to the classic problem of predicting annual sunspots activity.
      Baselevel predictors are drawn from a class of recurrent neural networks.
      Normalized mean squared errors of 0.064 and 0.19 for the conventional test
      intervals of 1921-1955 and 1956-1979, respectively, improve upon previously
      published results. The strategy has also been used to accurately forecast the
      behaviour of a synthetic system which makes random transitions between two states
      of low-dimensional chaos.

PMID- 8735384
TI  - Fractal representation of the immune B cell repertoire.
AB  - The immune repertoire is characterized by a complex and dynamic organization.
      Here I suggest, based on the presence of well-defined immune reactivity patterns
      (RP) analyzed using a linguistic analogy, that the B cell repertoires could
      possess a fractal structure. A simple estimation method of the fractal dimension
      (D) for a given immune B repertoire was developed, and D demonstrated to be an
      useful tool to define what complexity is regarding the immune repertoire, and to
      evaluate the complexity level of the immune B repertoire among age-structured
      groups of mice sensitized with the hemagglutinin (HA) molecule of influenza
      virus. Also, since a fractal-linguistic point of view, considerations are made
      about the ontogeny, connectivity, chaotic regimes, and size of the immune
      repertoire. Fractal analysis indicates that the immune repertoire shows a Zipf
      like scaling behavior, a statistical property of natural languages. This result
      suggests that immune repertoire is structured like a powerful language.

PMID- 8735385
TI  - A simple model for the statistics of events in idiotypic networks.
AB  - A simple random graph model of idiotypic networks is introduced: this model
      allows (1) to evaluate the stability of the network dynamics' fixed points, and
      (2) to compute the statistics of events triggered in response to the arrival of
      new molecules (metadynamics) using a dynamic mean-field approximation based on
      the theory of branching processes. It is shown that (1) the network dynamics is
      unlikely to have many stable fixed points in a strict sense, but that (2) the
      reorganizations which the network undergoes owing to the metadynamics are always
      subcritical if plausible figures are injected into the model. In other words the
      distance between successive (unstable or weakly stable) fixed points is
      relatively small, so that the overall behavior is stable.

PMID- 8735386
TI  - Enzyme activity regulation by an outer physical signal.
AB  - The main principles and methods of creating artificial systems with the
      directional regulation of enzyme activity by an outer physical signal are
      discussed. We are presenting some experimental results for the systems working in
      the necessary regime and responding to light and temperature.

PMID- 8735388
TI  - Smoothing representation of fitness landscapes--the genotype-phenotype map of
      evolution.
AB  - We investigate a simple evolutionary game of sequences and demonstrate at this
      example the structure of fitness landscapes in discrete problems. We show the
      smoothing action of the genotype-phenotype mapping which makes evolution
      feasible. Further we propose the density of sequence states as a classifying
      measure of fitness landscapes.

PMID- 8735387
TI  - Oscillatory, stochastic and chaotic growth rate fluctuations in
      permittistatically controlled yeast cultures.
AB  - We describe a continuous culture system related to the turbidostat, but using a
      feedback system based on biomass estimation from the dielectric permittivity of
      the cell suspension rather than its optical density. It is shown that this system
      provides an excellent method of maintaining a constant biomass level within a
      fermentor. The computer-controlled system was able to effect the essentially
      continuous registration of growth rate by monitoring the rate of medium addition
      via the time-dependent activity of the pump. At some biomass setpoints for
      aerobically grown cultures of baker's yeast substantial time-dependent
      fluctuations in the growth rate of the culture were thereby observed. At some
      biomass setpoints, however, or under anaerobic conditions, or when using a non
      Crabtree yeast, the growth rate was constant, indicating that the fluctuations
      were inherent to the biological system and not simply a property of the fermentor
      and control system. A variety of time series analyses (Fourier transformations,
      Hurst and Lyapunov exponents, the determination of embedding dimension, and non
      linear time series predictions based on the methodology of Sugihara and May) were
      used to demonstrate, for the first time, that as well as stochastic and periodic
      components these fluctuations exhibited deterministic chaos. 'Trivial predictors'
      were unable to give accurate predictions of the growth rate in these cultures.
      The growth rate fluctuations were studied further by means of offline
      measurements of changes in percentage viability, bud count, and in the external
      ethanol and glucose concentrations; these data and other evidence suggested that
      the growth rate fluctuations were closely linked to the primary respiro
      fermentative metabolism of this organism. The identification of chaotic growth
      rates in cell cultures suggests that there may be novel methods for controlling
      the growth of such cultures.

PMID- 8735389
TI  - Frequency analysis of amino acids in the recognition regions of T-cell receptors.
AB  - In immunoglobulins (Igs), key amino acids in the Complementarity Determining
      Regions (CDR) are responsible for maintaining specific conformations called
      canonical structures. In T-cell receptors (TCRs), protein members of the Ig
      superfamily, the corresponding residues for maintaining these canonical
      structures have not been found. In previous studies we have found in Igs that the
      frequency of use of amino acids in some positions of the CDRs follows an inverse
      power law distribution, while the frequency of amino acids in the rest of the
      positions of the CDRs follows an exponential law distribution. The positions that
      follow the inverse power law distribution are precisely those involved in
      maintaining the canonical structures, while those positions for which the
      distribution fits the exponential distribution are those that should be properly
      involved in the recognition mechanism. In this paper, when the same analysis is
      applied to the use frequency of amino acids on the CDRs of TCRs, it is found that
      some positions that have been previously identified as having a structural role
      are those fitting the inverse power law. That finding combined with the
      cooperative or long-range interaction properties of systems that follow the
      inverse power law leads us to propose that the lack of determined key residues in
      certain positions is compensated by "equivalent' residues in other positions
      within the CDRs in order to maintain the canonical structures. Other positions
      that follow the exponential distribution are those which can be involved in the
      recognition process. These results coincide with a computer-generated model of
      TCR/peptide/MHC interaction previously published by the authors.

PMID- 8735390
TI  - Antibiotic prophylaxis and head and neck surgery--what about pulmonary
      complications?

PMID- 8735391
TI  - Pain after tonsillectomy.

PMID- 8735392
TI  - Laser technology in research, diagnosis and therapy in rhinology.

PMID- 8735393
TI  - Augmentation mentoplasty with solid silicone.
AB  - Chin retrusion is important to the facial plastic surgeon, as it is a commonly
      encountered defect in patients seeking rhinoplasty. Careful pre-operative
      evaluation may identify patients who could benefit from concurrent augmentation
      mentoplasty. Augmentation mentoplasty using pre-formed silicone implants, placed
      sub-periosteally using an extraoral approach in a total of 40 patients were
      studied. The procedure proved to be relatively straightforward, rewarding and
      associated with very little morbidity. Hard silicone appears to be a reliable and
      safe implant material for augmentation mentoplasty in terms of host tolerance,
      including infection. There were no clinical side-effects from the minimal bone
      resorption which could be noted in eight out of 13 patients studied
      radiographically.

PMID- 8735394
TI  - The differentiation of snoring mechanisms using sound analysis.
AB  - Ten subjects known to suffer from heavy snoring but not obstructive sleep apnoea
      were studied using the technique of sleep nasendoscopy. The mechanism of snoring
      was noted for each and sound recordings of the snoring noise were made. Six
      subjects were observed to snore using their soft palate only, three snored using
      only their tongue base and one snored using a combination of palate and tongue
      base. The sound recordings were subjected to computer analysis of waveform and
      frequency. Palatal flutter snoring and tongue base snoring appear to have
      distinct waveform and frequency patterns which allows them to be differentiated
      from each other.

PMID- 8735395
TI  - Measurement of health status in patients with vertigo.
AB  - In order to assess how much disability is caused by vertigo, health status scores
      of patients referred with dizziness or vertigo were compared with local
      population normative data and with the severity of illness, measured by a disease
      specific questionnaire. The questionnaires were administered by post to patients
      awaiting an ENT out-patient appointment. There was a strong correlation (P =
      0.001) between the eight dimensions of the SF-36 (Mos 36 item short-form health
      survey) and disease severity, measured by the Dizziness Handicap Inventory
      questionnaire. Compared with the general population, vertigo sufferers had
      significant role limitation due to physical problems and social functioning (men)
      and physical problems and vitality (women). General health status is
      significantly affected by both the presence and severity of vertigo and the SF-36
      may prove useful in assessing outcomes.

PMID- 8735396
TI  - Lignocaine with adrenaline: is it as effective as cocaine in rhinological
      practice?
AB  - This double-blind study compares the effectiveness of two local anaesthetics with
      vasoconstrictive activity (10% cocaine and 4% lignocaine with adrenaline 1:1000)
      used in the nose. Anterior rhinomanometry was used to assess changes in nasal
      mucosal blood volume from a reduction in congestion of the nasal mucosa with a
      resulting reduction in nasal resistance. Nasendoscopy was then performed and the
      degree of subjective discomfort evaluated. Twenty patients presenting with nasal
      obstruction but without evidence of structural disease and nine healthy
      volunteers were entered into the study. Each received 10% cocaine in one nostril,
      and 4% lignocaine with adrenaline (1:1000) in the other in a double-blind study.
      In all subjects, there was a significant reduction of nasal resistance after the
      administration of both drugs (P < 0.005). The anaesthetic effects of both agents
      were comparable with subjects reporting only a mild discomfort during
      nasendoscopy. We conclude from this study that 4% lignocaine with adrenaline
      (1:1000) solution is as effective as 10% cocaine.

PMID- 8735397
TI  - Snoring, apnoea and ENT symptoms in the paediatric community.
AB  - This study was designed to determine the prevalence of snoring and assess the
      extent of associated ENT symptoms in children up to 10 years of age. A
      questionnaire was presented to the parents of 245 children chosen at random from
      the General Practice list of the town of Frome, Somerset, UK. The prevalence of
      snoring was found to be 27%. This increased to 47% in the presence of an upper
      respiratory infection. Snoring was found to be significantly (P < 0.001)
      associated with a history of poor hearing, restless sleep, and having a cold.
      Less significant (P < 0.01) associations occurred with parental smoking, eczema,
      sleep talking, moving around the bed at night, sore throats, having a runny nose
      and mouth breathing. Snoring is a common symptom in children up to 10 years of
      age. Without evidence of other ENT disease the snoring child does not require
      referral to an ENT department for further investigation.

PMID- 8735398
TI  - Evaluation of risk factors for stomal recurrence after total laryngectomy.
AB  - The development of a stomal recurrence after total laryngectomy is a complication
      with a dismal prognosis. The risk factors and mechanisms involved are still not
      well understood. In this review of 352 patients, 21 (6%) developed a stomal
      recurrence. We studied the group of 74 patients (21%) with subglottic involvement
      separately. There was no significant difference in the rate of stomal recurrence
      in those with emergency tracheostomy (23.3%) as compared with those with intra
      operative tracheostomy (18.2%). Stomal recurrence was more strongly associated
      with subglottic involvement itself (20.3%) and T4 stage (15.3%). The findings
      suggest that submucosal extension and lymph node metastases are probably more
      important mechanisms of stomal recurrence than cancer cell implantation.

PMID- 8735399
TI  - Long-term results of trimming of the inferior turbinates.
AB  - The long-term benefit of trimming of the inferior turbinates for nasal
      obstruction is unclear and our aim was to assess this. Fourteen patients who had
      had pre-operative nasal symptom scores and anterior rhinomanometry prior to
      inferior turbinate resection were reassessed at least 7 years post-operatively.
      Both nasal symptom scores for obstruction and nasal resistance had increased
      significantly in the intervening time period. Nasal crusting and hypertrophy of
      the cut inferior turbinate are considered to be responsible for this. Patients
      should be warned some degree of nasal obstruction may recur postoperatively.

PMID- 8735400
TI  - Direct hearing aid referrals: a prospective study.
AB  - General practitioners from a designated catchment area were invited to
      participate in a direct hearing aid referral project and were issued with a
      standard referral form outlining the criteria for referral. A total of 175
      patients was referred with a fully completed referral form and were initially
      assessed by a senior audiology technician or higher grade. A total of 135
      patients (77%) was suitable for hearing aid fitting and 40 (23%) were considered
      to be inappropriate referrals, of which 17 (9.7%) required further referral for
      an ENT opinion. For the purpose of safety, each patient was independently
      examined by an ENT doctor. The management decisions of the audiology technicians
      were in total agreement with those of the ENT doctors. Our results also suggested
      that patients below the age of 60 are generally unsuitable for direct referral.

PMID- 8735401
TI  - Antigen retrieval: p53 staining in benign, pre-malignant and malignant tissues of
      the larynx.
AB  - Antigen retrieval techniques have been reported to increase p53 detection. Using
      an antigen retrieval technique applied to immunohistochemistry, a study was
      performed on 67 laryngeal lesions (21 benign, 16 carcinoma in situ, 30 squamous
      cell carcinoma). p53 staining was observed in 30% of carcinoma in situ specimens
      and 53% of squamous cell carcinomas but was not detected prior to antigen
      retrieval in any benign lesion. However, over-expression of p53 was identified in
      92.5% of benign lesions after antigen retrieval using the microwave oven heating.
      There was also increased p53 staining in both the carcinoma in situ (43.7%) and
      squamous cell carcinomas (30.0%) after antigen retrieval. We conclude that
      antigen retrieval using microwave oven heating increases immunohistochemical
      detection of p53 such that positive staining is observed in benign conditions. We
      postulate that this apparent over-expression is a manifestation of the wild-type
      protein, which may be found in more evidence in basal cells than suprabasal
      cells. Our results thus offer a cautionary note to such studies involving
      squamous cell cancers that attempt to correlate p53 over-expression with clinical
      parameters.

PMID- 8735402
TI  - Head stabilization in peripheral vestibular syndromes.
AB  - In classical posturography the standing position has been evaluated by recording
      the postural sway on a force-plate and measuring some parameters such as surface
      and velocity (Platform or P-recording). The postural sway not only results in
      forces exerted on the support surface by the feet, but the head also participates
      in the movements of this postural sway. For recording of the head movements (H
      recording), a lightbulb is placed on top of the head and the described light-path
      is recorded by a TV camera. Such an H-recording can be achieved simultaneously
      with the platform-recording. A comparative study indicates that, for some
      patients differences could be found between H- and P-recordings, for others not.
      The H-recording, in fact, gives information about the stabilization of the head,
      compared with the stability on the platform (P-recording). The importance of the
      information furnished by the double recording in Static Posturography type IV
      (SPGIV) can be deduced from the number of patients showing one or more
      differences between the types of recording. Nearly 70% showed a difference in at
      least one test. In fact, 55% showed it in two or more tests. In half of the
      tests, considered separately, a difference was noted. The differences observed
      provide complementary information in this combined recording. If the H-recording
      were to be used as a separate technique, it has to be born in mind that the
      results are certainly not always the same as when using P-recording, as in
      classical posturography.

PMID- 8735403
TI  - The incidence of bacteria in middle ear effusions.
AB  - Otitis media with effusion (OME) is a common condition in paediatric ENT
      practice. Whilst surgical management is in many cases the mainstay of treatment
      for resistant OME, the use of antibiotics has been advocated by some authorities.
      Over one quarter of middle ear effusions analysed in this study contained
      potentially pathogenic bacteria. Antibiotics may be of value in the treatment of
      OME in these children.

PMID- 8735404
TI  - The role of the Davis graft technique in the treatment of chronic post
      mastoidectomy otorrhoea.
AB  - The effect of grafting mastoid cavities with small Davis cutaneous pinch grafts
      was assessed in 15 patients. Following revision of the cavity and Davis pinch
      grafting the resultant cavity was completely dry in 13 patients (87%) over a
      period ranging from 1 to 30 months with a mean of 7.3 months, with five becoming
      dry within 1 month. Patient satisfaction with respect to reduction in discharge
      and smell was excellent (87%). We believe that the Davis graft technique has a
      beneficial role in persistent post-mastoidectomy otorrhoea especially when
      previous standard revision techniques have failed.

PMID- 8735405
TI  - Audiometric findings in children with chronic suppurative otitis media without
      cholesteatoma.
AB  - Chronic suppurative otitis media without cholesteatoma (CSOMWC) is usually
      associated with an increase in air conduction thresholds. However, only a few
      investigations reported on loss of cochlear function in the pediatric population.
      We undertook a prospective study in order to further delineate air and bone
      conduction levels in children with CSOMWC and the possible relationship between
      sensorineural hearing loss (SNHL) and other clinical characteristics that might
      reflect the extent of disease. Eighty-seven children were enrolled, 40 of which
      had bilateral disease. Hence, the total number of diseased ears tested was 127.
      Audiometric studies were performed three days after achieving a 'dry' ear
      following medical treatment. We found no statistically significant differences
      between the bone conduction threshold tested in ears with CSOMWC and control
      ears. This was also the case in 47 children with unilateral disease when cochlear
      function was investigated in the diseased and uninvolved ear in the same patient.
      Clinical correlation showed no association between age, sex, duration of otorrhea
      and presence of granulation or polyps and the degree of cochlear loss. Our study
      shows that CSOMWC in children has little effect on cochlear function.

PMID- 8735407
TI  - Fo-perturbation and Fo/loudness dynamics in voices of normal children, with and
      without education in singing.
AB  - Sustained phonations were compared in two groups of children (aged 7-12), one
      with special artistic voice education and one from a normal school, without voice
      complaints or problems. The hypothesis of specific (better) biomechanical vocal
      fold properties in the first group is confronted with the hypothesis of
      differences solely related to training of voice control. In both groups, Fo
      aperiodicity was measured in a sustained phonation at 3 different SPL levels. As
      a general rule, aperiodicity clearly decreases when the voice becomes louder.
      Aperiodicity is highly significantly lower, at all SPL-levels, in children with
      trained singing voices: this implies better mechanical properties of the vocal
      oscillator. The Fo/SPL relation on a sustained /a:/ does not differ in trained
      and untrained children's voices: out of singing context, trained children do not
      spontaneously control the Fo/SPL dynamics differently from untrained children.
      The higher regularity of vocal fold pulses is not related to the duration of
      training.

PMID- 8735406
TI  - Microbial flora of the subglottis in intubated pediatric patients.
AB  - Infection of the intubated subglottis is felt to be one of the many factors
      involved in the pathogenesis of acquired cicatricial subglottic stenosis. The
      precise role of infection is unclear and the microbial flora has not been
      established. An analysis of subglottic culture material, from 22 intubated
      pediatric patients undergoing tracheotomy, has been performed to establish the
      nature of the subglottic microbial flora. Fifty-nine isolates were found,
      including 19 types of organisms. The number of isolates per patient ranged from
      one to eight, with an average of 2.7 isolates per patient. The most common
      isolates in the 22 patients were alpha-hemolytic Streptococcus viridans (17
      isolates-77%), Neisseria sp. (6 isolates-27%), Pseudomonas sp. (5 isolates-22%),
      and coagulase negative Staphylococcus sp. (5 isolates-22%). This data indicates
      that colonization of the subglottis in intubated pediatric patients is
      polymicrobial in nature. alpha-Hemolytic Streptococcus viridans and Neisseria sp.
      were most common, with a shift in cultured flora towards Pseudomonas sp. in
      patients intubated for more than 10 days. In view of this, antimicrobial therapy
      may be of benefit in preventing acquired cicatricial subglottic stenosis.

PMID- 8735408
TI  - Spontaneous immunoglobulin production by adenoidal and tonsillar lymphocytes in
      relation to age and otitis media with effusion.
AB  - Spontaneous immunoglobulin (Ig) production by autologous adenoidal and tonsillar
      lymphocytes cultured without any mitogen was measured by an enzyme-linked
      immunosorbent assay (ELISA) in 18 children with or without otitis media with
      effusion (OME). Both IgG and IgA levels synthesized by adenoidal or tonsillar
      lymphocytes significantly increased with age. The average concentrations of IgG
      and IgA produced by adenoidal lymphocytes from children with OME were
      significantly lower than those from children without OME. Adenoidal lymphocytes
      produced IgG and IgM at significantly lower levels than autologous tonsillar
      lymphocytes did in children with OME. In contrast, no significant difference
      between adenoidal and tonsillar lymphocytes was seen on Ig production for any
      isotypes in children without OME. These results may indicate immunological
      impairment of the adenoids associated with OME.

PMID- 8735409
TI  - Otitis media: relationship to tonsillitis, sinusitis and atopic diseases.
AB  - In order to estimate the co-morbidity between ear infections and related
      childhood diseases, data about the occurrence of recurrent ear infections,
      tonsillitis, sinusitis and atopic diseases from a population based sample of 7992
      Norwegian twins were analysed. Correlational results revealed two general
      clusters, one consisting of upper respiratory tract infections (URI), the other
      defined by the atopic diseases. Overall, associations between the diseases were
      greater in males. The sizes of the correlations within each subgroup of
      infections were moderate, but significant, ranging from 0.191 to 0.363. Similar
      results were found for the relationship within the subgroup of atopies, with
      correlations ranging from 0.134 to 0.466. The correlations between the infectious
      and atopic diseases were weak. Both ear infections and tonsillitis seemed to be
      predisposing factors for sinusitis. The relative risk of sinusitis among
      individuals with a history of ear infections was 3.4 (1.9-6.2) and 1.9 (1.2-3.0)
      for males and females, respectively. Ear infections conferred an increase in
      tonsillitis, estimated at 2.3 (1.6-3.0) and 2.0 (1.2-3.6) for males and females,
      respectively. In conclusion, the present study finds evidence for a common
      predisposition of upper respiratory infections as well as for atopic diseases,
      but only moderate correlation between the subgroups. Specifically, between ear
      infections and hay fever there was no covariation.

PMID- 8735410
TI  - Audiovestibular sequelae of congenital cytomegalovirus infection in 3 children
      presumably representing 3 symptomatically different types of delayed
      endolymphatic hydrops.
AB  - Three cases of congenital cytomegalovirus (CMV) infection with long-term
      audiovestibular sequelae are presented. Case 1 had no hearing in one ear and
      severe progressive hearing loss in the other ear; he showed vestibular symptoms
      at the age of 4.5 years. Case 2 had severe but stationary hearing loss in one ear
      and showed hearing impairment symptoms in the other ear at 9-13 years of age.
      Case 3 did not have hearing impairment symptoms, or vestibular symptoms, but was
      found to have severe progressive hearing loss from the age of 15 months onwards,
      which led to profound deafness at the age of 2 years and vestibular areflexia at
      or before the age of 4 years. These cases may represent 3 symptomatically
      different types of delayed endolabyrinthine hydrops. Type 1 (ipsilateral hydrops)
      incorporates vestibular symptoms only because of a lack of hearing in the
      offending labyrinth. Type 2 (contralateral hydrops) incorporates hearing
      impairment symptoms only because of a lack of vestibular function on both sides
      and type 3 does not incorporate hearing impairment symptoms or vestibular
      symptoms (other than those relating to a complete lack of function). Given the
      present findings, those described by Weiss and Ronis (Trans. Pa. Acad. Opthalmol.
      Otolaryngol., 30 (1977) 52-54) in one case and other reported findings relating
      to histopathological or imaging methods in somewhat similar cases, it seems
      appropriate to include congenital CMV infection in the differential diagnosis of
      delayed endolymphatic hydrops.

PMID- 8735411
TI  - Database for sensorineural hearing loss.
AB  - We are creating a bank of EBV immortalized lymphoblast cells and extracted DNA
      taken from the blood of deaf children and their relatives, in order to study the
      molecular basis of hereditary deafness. We have established a corresponding
      database for sensorineural hearing loss that records clinical data for each
      entered specimen. The purpose of this paper is to present the content and design
      of the computerized relational database. The data model is designed first to
      identify known etiologies of deafness, either acquired or syndromic, and then to
      characterize the clinical features of the deaf individual, and both their
      affected and non-affected family members. The application operates in a graphical
      environment of visual prompts and message panels. The database is organized by
      sections which record demographic data, presenting complaints, otologic history,
      birth and perinatal history, developmental history, symptoms of chronic airway
      obstruction, family history, neurologic history, congenital infections,
      hospitalizations and surgical history, medication history, vestibular findings,
      audiometry, radiology, medical conditions and syndromes and physical examination.
      The database was developed on a commercially available software product. Our
      database is presented as a model for use by other clinicians and investigators.

PMID- 8735412
TI  - Auditory nerve-brainstem responses in cystic fibrosis patients.
AB  - We conducted a study in 30 children with cystic fibrosis (CF) to determine if
      their hearing had been affected. Their ages ranged between 2 to 17 years and they
      were studied by means of complete audiologic evaluation and brainstem evoked
      response audiometry (BERA). Twenty of them had received some ototoxic drugs for
      variable periods. The results showed that there was no significant correlation
      between CF and BERA findings. The findings indicated that, except a few middle
      ear problems such as serous otitis media, CF did not affect hearing status of the
      CF children per se.

PMID- 8735413
TI  - Treatment of aspiration or tracheostomy-associated pneumonia in neurologically
      impaired children: effect of antimicrobials effective against anaerobic bacteria.
AB  - The purpose of the present study was to retrospectively review the antibiotic
      therapy of aspiration or tracheostomy-associated pneumonia in 57 neurologically
      impaired children (NIC). The antimicrobials used were either ticarcillin
      clavulanate or clindamycin, which are effective against penicillin-resistant
      anaerobic bacteria, or ceftriaxone, which is less effective against these
      organisms. In those with aspiration pneumonia, a satisfactory clinical and
      microbiological response was observed in 8/9 (89%) patients who received
      ticarcillin-clavulanate, and 10/11 (91%) who received clindamycin with or without
      ceftazidime, as compared to 7/14 (50%) who received ceftriaxone (P < 0.05). For
      those who experienced tracheostomy-associated pneumonia, a positive response to
      therapy was observed in 5/6 (83%) who received ticarcillin-clavulanate, and 7/7
      (100%) who received clindamycin with or without ceftazidime, as opposed to 4/10
      (40%) who were treated with ceftriaxone (P < 0.05). The duration of fever was
      longer in both cases for those who received ceftriaxone. To summarize, this study
      illustrates the superiority of antimicrobials effective against penicillin
      resistant anaerobic bacteria, as compared to an antibiotic without such coverage,
      in the therapy of aspiration or tracheostomy-associated pneumonia in NIC.

PMID- 8735414
TI  - The effect of level of feed intake on the pharmacokinetic disposition and
      efficacy of ivermectin in sheep.
AB  - The kinetic disposition of orally administered [3H]-Ivermectin (IVM) was examined
      in sheep in which the feed intake was maintained at either 800 or 400 g/day. The
      [3H]-metabolites were almost completely associated with particulate digesta in
      the rumen. In the low feed intake group the digesta flow was slower than in sheep
      on high feed intake. This resulted in an extended residence time and greater
      availability of IVM and its metabolites. The anthelmintic efficacy of IVM was
      then examined in sheep in which feed intake was reduced from 800 g/day to 400
      g/36 h prior to and 36 h after IVM administration. In sheep with reduced intake
      97% of IVM-resistant Haemonchus contortus were removed, compared with 53% in
      sheep maintained on high feed intake.

PMID- 8735415
TI  - Pharmacokinetic-pharmacodynamic model for spiramycin in staphylococcal mastitis.
AB  - Simultaneous pharmacokinetic-pharmacodynamic (PK/PD) modelling for spiramycin in
      staphylococcal infections of the mammary gland of cows was used to predict the
      efficacy of spiramycin. A differential equation derived from the Zhi model was
      fitted to an in vitro killing curve and post-antibiotic effect determination. A
      seven-compartment PK model, in which 4 compartments representing each quarter of
      the mammary gland which was considered to be the effect compartment, was
      included. The PD model linked to the PK model was able to describe the in vivo
      spiramycin effect against Staphylococcus aureus. The parameters calculated from
      in vitro data predicted a rapid decrease for the first 12-24 h, and regrowth
      within 72 h following the treatment, whereas in vivo the bacterial effect was
      much less after 24 h than that predicted by the in vitro data. PK/PD modelling
      permitted the simulation of various doses to optimize the efficacy of the
      antibiotic, taking into account such dynamic parameters as bacterial growth rate
      constant, bacterial killing rate constant and the Michaelis-Menten type
      saturation constant. An optimal dosage regimen of 20000 IU/kg per day for 3 days
      was predicted for the treatment of Staphylococcus aureus mastitis.

PMID- 8735416
TI  - The pharmacokinetics of salicylate in dairy cattle are not altered by
      simultaneous intravenous ceftiofur sodium and DL-lysine-acetyl salicylate
      (aspirin).
AB  - This study evaluated potential alterations to the pharmacokinetics of salicylate
      by concurrently administered ceftiofur sodium. The trial design was a cross-over
      using 10 non-lactating, non-pregnant dairy cows. In the first period each cow
      received intravenously (i.v.) 26 mg/kg of DL-lysine acetyl salicylate (aspirin)
      followed immediately by 2 mg/kg ceftiofur sodium. In the second period each cow
      received 26 mg/kg of aspirin i.v. Plasma samples were harvested for determination
      of salicylate concentration by HPLC. The data best fitted a single compartment
      open model, using weighted non-linear regression. No alterations to the
      pharmacokinetic parameters of salicylate in cattle by concurrently administered
      ceftiofur sodium were detected (P < 0.05). Using 90% confidence intervals, and
      testing for changes of > 20%, control values, elimination half-life (t1/2),
      apparent volume of distribution (Vd), area under the plasma concentration versus
      time curve (AUC) and mean residence time (MRT) were not altered. For control
      animals the elimination rate constant (k(el)) and total body clearance (Cl) were
      1.35 +/- 0.43 h-1 and 20.2 +/- 6.1 ml/h.kg respectively (mean +/- SD). Since
      ceftiofur sodium did not affect the pharmacokinetics of salicylate, dose regimens
      for aspirin in cattle need not be altered when ceftiofur sodium is administered
      concurrently.

PMID- 8735417
TI  - Single dose pharmacokinetics of medetomidine in sheep.
AB  - The pharmacokinetics of medetomidine hydrochloride (Domitor) administered at a
      single dose of 15 micrograms/kg i.v. in sheep are described. Plasma medetomidine
      concentrations were determined using a sensitive radioreceptor assay technique,
      capable of also measuring metabolites which would bind to alpha 2 adrenergic
      receptors. Medetomidine was rapidly distributed, with a half-life of distribution
      of 4.65 +/- 0.65 min. The apparent volume of distribution was 2.69 +/- 0.62 L/kg,
      while elimination half-life was 37.85 +/- 2.84 min. Total body clearance varied
      between 16.29 and 151.81 mL/min.kg. Pharmacological effects of medetomidine
      paralleled its plasma concentration.

PMID- 8735418
TI  - Pharmacokinetics of caffeine in the oestrogen-implanted ovariectomized ewe.
AB  - The disposition kinetics of caffeine and its metabolites theophylline,
      theobromine and paraxanthine in the oestrogen-implanted ovariectomized ewe
      following single intravenous doses of 5, 10, 15 or 20 mg/kg caffeine are
      described in this paper. Blood was collected at 5, 30 and 60 min, and at 3, 6, 8,
      12, 24, 48, 72, 96, 120, 144, 192 and 240 h after dosing. Caffeine concentrations
      peaked within 30 min of administration but remained in a plateau phase for 3-6 h
      before declining over a prolonged period of time. For caffeine the mean
      elimination half-life was calculated to be 47 h. Detectable caffeine
      concentrations remained for 10 days after administration in all groups. The area
      under the plasma concentration-time curve (AUC) values were used to compare
      tissue caffeine exposure and were, approximately, linearly related to dose.
      Metabolite concentrations were maintained at peak and near peak concentrations
      for 6-24 h after caffeine administration followed by prolonged elimination.
      Because of significant species differences in drug elimination rates, it is
      concluded that the ewe is not a suitable animal model in the clinical context.
      However, the sheep may well provide insights into caffeine's mechanism of action
      of relevance to veterinary drug research.

PMID- 8735419
TI  - In vitro activity of fifteen antimicrobial agents against methicillin-resistant
      and methicillin-susceptible Staphylococcus intermedius.
AB  - In this study the susceptibility of 91 methicillin-resistant and -susceptible
      Staphylococcus intermedius strains (MRSI and MSSI, respectively) against 15
      antimicrobial agents was determined. The activity of the antimicrobial agents was
      studied at pH 7.2 and pH 8.5. Methicillin was more active at pH 7.2 (28 strains
      methicillin-resistant) than at pH 8.5 (55 strains methicillin-resistant).
      Gentamicin showed excellent activity, with only 3 strains resistant at pH 8.5.
      However, gentamicin would have to be administered parenterally. Oxytetracycline
      cannot be recommended for treatment of canine staphylococcal dermatitis, due to
      the high percentage (over 25%) of strains that were found to be resistant.
      Clindamycin showed little activity in inhibiting growth of the strains studied,
      the percent resistance at pH 7.2 was 93.4%. Rifampin behaved differently at the
      two pH values. However, a close relationship was noted between methicillin
      resistant and rifampin-resistant strains, particularly at the lower pH. Of the
      fluoroquinolones, ciprofloxacin or enrofloxacin would be a good useful
      alternative for the treatment of methicillin-resistant strains of S. intermedius.
      Lastly, very high resistance to sulphamethoxypyridazine was found, as was the
      case with trimethoprim and a combination of trimethoprim/sulphamethoxypyridazine,
      against not only MRSI but also MSSI strains.

PMID- 8735420
TI  - The actions of medetomidine may not be mediated exclusively by alpha 2
      adrenoceptors in the equine saphenous vein.
AB  - Spirals of endothelially denuded equine saphenous vein were used to study the pre
      and post-junctional effects of medetomidine in vitro. The pD2 values were
      calculated for noradrenaline (6.7 +/- 0.1), phenylephrine (5.6 +/- 0.1), BHT 920
      (6.2 +/- 0.2) and UK 14304 (5.7 +/- 0.2). Medetomidine produced a biphasic
      response, with a pD(2)1 of 8.2 +/- 0.1 and a pD(2)2 of 5.7 +/- 0.1 in the equine
      saphenous vein (n = 6). Prazosin (10(-7) M) significantly shifted the second
      phase of the medetomidine concentration-response curve to the right (pD(2)1 was
      8.1 +/- 0.2 and pD(2)2 was 5.0 +/- 0.2, P < 0.05). Rings of equine saphenous vein
      were electrically stimulated to investigate the pre-junctional effects of
      medetomidine. Increasing concentrations of the alpha 2-adrenoceptor agonist BHT
      920 reduced the response to electrical stimulation in a concentration dependent
      manner to a maximum of 40 +/- 5%, whereas medetomidine (0.1-100 nM) caused a
      concentration dependent enhancement to a maximum of 490 +/- 150%. These results
      suggest alpha 1- and alpha 2-adrenoceptors are functional in the equine saphenous
      vein, but that medetomidine is not acting exclusively as an alpha 2-adrenoceptor
      agonist.

PMID- 8735421
TI  - Norfloxacin nicotinate pharmacokinetics in unweaned and weaned calves.
AB  - The pharmacokinetics of norfloxacin nicotinate were investigated in unweaned and
      weaned calves. Following intravenous administration of 7.5 and 15 mg/kg
      (calculated as norfloxacin base) the clearance values were 8.5 +/- 2.0 or 7.7 +/-
      1.2 mL/min.kg (unweaned calves) and 11.7 +/- 3.2 or 16.1 +/- 3.3 mL/min.kg
      (weaned calves). Norfloxacin mean residence time and volume of distribution
      values were 211 +/- 33 or 227 +/- 41 min (unweaned calves) and 185 +/- 79 or 128
      +/- 18 minutes (weaned calves), and 1.8 +/- 0.3 or 1.7 +/- 0.1 L/kg (unweaned
      calves) and 2.0 +/- 0.7 or 2.1 +/- 0.7 L/kg (weaned calves) following
      administration of the lower and higher dose, respectively. These results
      indicated that norfloxacin pharmacokinetics were similar at a dose range of 7.5
      15 mg/kg. However, a significant difference was observed in clearance, mean
      residence time and the half-life values between the unweaned and weaned calves.
      The only major pharmacokinetic parameter which did not show a significant
      difference between the investigated groups was the volume of distribution. The
      pharmacokinetic differences between the non-ruminating (unweaned) and ruminating
      (weaned) animals seemed to result from changes in drug clearance. The absorption
      rate after intramuscular administration appeared to change as a result of dose
      increase. Norfloxacin bioavailability following intramuscular administration
      ranged from 73 to 106%. The results suggested that larger injection volumes may
      reduce the extent of absorption.

PMID- 8735423
TI  - Bioavailability, pharmacokinetics, and tissue distribution of 14C homidium after
      parenteral administration to Boran cattle.
AB  - The absorption, distribution and elimination characteristics of 14C homidium have
      been described in non-infected and Trypanosoma congolense-infected cattle treated
      with 14C homidium chloride by either intramuscular (i.m.) or intravenous (i.v.)
      injection at a dose level of 1 mg/kg body weight. Results show that the mean (+/
      SD) elimination of the drug from plasma followed a biexponential process, with
      half-lives of 0.084 +/- 0.006 h and 97.66 +/- 16.28 h for the distribution and
      elimination phases after intravenous injection, respectively. Bioavailability of
      the intramuscular dose was 62.5% and 57.8% in non-infected and trypanosome
      infected cattle, respectively. Absorption was rapid, with a tmax of 15 min and a
      mean Cmax (+/-SD) of 268.4 +/- 4.09 ng/mL following the intramuscular dose in non
      infected cattle. The major route of excretion was via faeces. Approximately 90%
      of the total dose given to non-infected i.m.-treated cattle was excreted within
      14 days. Following intramuscular administration of the drug, residues remained
      high in the major excretory organs, with the liver having concentrations of 1411
      and 1199 ng/g after 14 and 28 days, respectively. Over the same period, the
      values in the kidneys were 649 and 448 ng/g. Concentrations in the liver 14 and
      21 days following i.v. treatment were 2195 and 2454 ng/g, respectively. These
      results show that there was no significant difference in liver drug residues
      between 14 and 21 days, or 28 days depending on the treatment given, suggesting
      that once the drug is in this organ, it is released back into the circulation at
      an extremely slow rate.

PMID- 8735422
TI  - Binding of sulphamethazine to pig plasma proteins and albumin.
AB  - The interaction of sulphamethazine (SMZ) with pig plasma proteins and albumin was
      studied by ultrafiltration and equilibrium dialysis. Binding to pig plasma
      proteins was monophasic (affinity approximately 9.0 mol/L x 10(3)) and the main
      binding protein was albumin. At 37 degrees C and pH 7.4, the affinity of SMZ for
      albumin was about 8.0 mol/L x 10(3) and the number of binding sites was estimated
      as 1.4. Increasing the temperature from 4 to 45 degrees C resulted in a seven
      fold decrease in affinity, and increasing pH from 6.0 to 8.0 enhanced affinity
      for pig albumin ten-fold. The free energy of binding (-delta G) and enthalpy
      change (-delta H) were around 5.5 and 5.1 Kcal/mol, respectively. The total
      entropy change (delta S) was small and positive, around 2 cal/mol/degree K.
      Studies with the fluorescent probes warfarin and dansylsarcosine, suggest that
      these bind to separate sites on porcine albumin. SMZ displaced both probes and
      inhibited the deacetylation of p-nitrophenyl acetate by pig albumin. We conclude
      that: (1) binding of SMZ to pig plasma proteins and albumin is weak; (2) the
      interaction with albumin is exothermic and enthalpy driven, and (3) pig albumin,
      like other mammalian albumins, appears to possess discrete binding sites for
      warfarin and dansylsarcosine. SMZ interacts with both these loci.

PMID- 8735424
TI  - Pharmacokinetics and pharmacodynamics of phenylbutazone and oxyphenbutazone in
      the donkey.

PMID- 8735425
TI  - Pharmacokinetics of nebulized sodium ceftiofur in calves.

PMID- 8735427
TI  - Pharmacokinetics of radiolabelled buffalo follicle-stimulating hormone (125I
      buFSH) in female buffalo calves (Bubalus bubalis).

PMID- 8735426
TI  - Systemic absorption of gentamicin following intramammary administration to cows
      with mastitis [correction of mastititis].

PMID- 8735428
TI  - Pharmacokinetics of gentamicin in llamas.

PMID- 8735429
TI  - The effects of submaximal exercise on the pharmacokinetics of furosemide in
      horses.

PMID- 8735430
TI  - Pharmacokinetics of gentamicin in donkeys.

PMID- 8735431
TI  - Relevance of intravenous cocaine use in relation to prevalence of HIV, hepatitis
      B and C virus markers among intravenous drug abusers in southern Italy.
AB  - The purpose of this study was to analyze the relationship between intravenous
      (i.v) drug use practices and the prevalence of human immunodeficiency virus
      (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) in 146 heterosexual
      male i.v. drug users (IVDUs) attending a methadone-maintainance treatment program
      in Catanzaro, Southern Italy. One hundred and forty-six heterosexual male IVDUs
      attending a methadone-maintainance treatment program in Catanzaro were
      interviewed in order to obtain the following information: age, number of drug
      injections (calculated by multiplying the mean number of daily injections by 365
      and then by the number of years of injections), number of injection equipment
      sharing partners in the last year, number of sexual partners in the last year and
      possible IV cocaine use. Their sera were studied for the presence of antibodies
      to HIV, HBV and HCV by commercial enzyme-linked-immuno-sorbent assays run in
      duplicate. HIV positive samples were confirmed by Western Blot assay. Sixteen per
      cent of IVDUs were anti-HIV positive, 40% were anti-HBc positive and 68% were
      anti-HCV positive. Twenty-three per cent were seronegative and 12% were
      seropositive for all 3 viral markers. Multiple logistic analysis of HIV, HBV and
      HCV seropositivities in relation to age, number of drug injections, i.v. cocaine
      use and presence of injection equipment-sharing partners in the last year, showed
      that: a) older age (more than 27 years) was significantly associated with all 3
      viral infections (mainly with HIV); b) i.v. cocaine use was associated with HBV,
      but even more with HIV; c) injection equipment-sharing partners in the last year
      was directly associated with HCV and inversely with HIV. No significant
      association was observed with the number of drug injections and the number of
      sexual partners. In conclusion, this study: a) demonstrates a difference of
      prevalence for HIV, HBV and HCV serum markers in this group of IVDUs from
      Catanzaro, Southern Italy; b) underlines the importance of i.v. cocaine use in
      the spreading of HIV; c) emphasizes the need of preventive strategies.

PMID- 8735432
TI  - Development and application of an ELISA for Goodpasture's disease based on sheep
      alpha 3(IV)NC1 domains.
AB  - A high titre of antibodies to collagenase-solubilised human glomerular basement
      membrane (CS-GBM) is almost pathognomic of Goodpasture's (anti-GBM) disease. In
      order to develop an assay independent of scarce human material, a molecule of
      approximately 26 kD corresponding to the C-terminal NC1 domain of the alpha 3
      chain of type IV collagen was purified from sheep GBM by gel filtration and
      reverse phase HPLC. This molecule was antigenic when assessed by inhibition
      studies, by immunoblotting, and as a ligand on ELISA plates. An ELISA using this
      sheep alpha 3(IV)NC1 preparation to detect circulating anti-GBM antibodies gave
      comparable results to the standard RIA using crude CS-GBM. Sera from patients
      with a variety of nephropathies other than Goodpasture's disease gave negative
      results. In a prospective study, 170 consecutive sera were analysed by both the
      ELISA and the RIA. Twenty seven specimens gave positive results in one or both of
      the assays. Eleven of these were confirmed as true positive results and all were
      correctly identified by the RIA. Two false negative results in the ELISA occurred
      in previously treated cases, and both sera were only weakly positive by RIA. The
      RIA gave 13 false positive results compared with five by ELISA. The ELISA using
      highly purified sheep antigen is a robust, reliable, and more specific
      alternative to immunoassays based on crude human antigen preparations.

PMID- 8735433
TI  - Effects of serum from HIV-infected subjects on the functional activity of
      polymorphonuclear neutrophils.
AB  - The oxidative capacity of polymorphonuclears neutrophils (PMN) was assessed in 17
      subjects with asymptomatic infection (AI), 16 patients with acquired
      immnunodeficiency syndrome (AIDS) and 12 healthy normal subjects using a
      quantitative Nitroblue Tetrazolium (NBT) reduction test. The effect of the serum
      of patients on the functional activity of normal and patients' PMN was also
      investigated. The NBT reduction non stimulated and stimulated with zymosan
      particles in presence of normal serum was similar to normal controls in both
      groups of patients. The serum from 11 out of the 17 AI subjects (65%) induced an
      increase while the serum from 8 out of the 16 AIDS patients (50%) induced a
      diminution in the stimulated NBT reduction in normal and patients' PMN. Those
      effects did no, appear to be related to complement C3 and circulating immune
      complexes levels. These results are indicating that PMN of HIV-seropositive
      patients do not present an intrinsic disfunction and that the impact of serum
      factor/s affects the normal functionalism of these cells depending on the
      infection stages.

PMID- 8735434
TI  - Possible low response of C-reactive protein production in eosinophilic pneumonia.
AB  - C-reactive protein (CRP) in the patients with eosinophilic pneumonia was examined
      compared with that of bacterial pneumonia. While no difference between
      erythrocyte sedimentation rate (ESR) in eosinophilic pneumonia (mean +/- SE: 74.5
      +/- 10.6 mm/hr) and that in bacterial pneumonia (86.2 + 7.7 mm/hr) was observed,
      serum CRP level (3.87 +/- 1.24 mg/dL) and alpha 2-macroglobulin level (182.53 +/-
      13.00 mg/dL) in eosinophilic pneumonia were lower in comparison with those in
      bacterial pneumonia (14.89 +/- 1.34 mg/dL, 315.65 +/- 11.54 mg/dL, respectively),
      suggesting that the pathogenesis of eosinophilic pneumonia might involve
      defective secretion of certain cytokine related to the production of acute-phase
      reactant proteins such as interleukin-6.

PMID- 8735435
TI  - Low levels of LTB4 in cerebrospinal fluid of AIDS patients with cryptococcal
      meningitis.
AB  - In this study we evaluated the release of leukotriene B4 (LTB4) in the
      cerebrospinal fluid (CSF) of 12 patients with Acquired Immunodeficiency Syndrome
      (AIDS), which disease was complicated by Cryptococcal Meninigitis and in CSF of
      12 control subjects with inflammatory and degenerative pathologies of the Central
      Nervous System (CNS). We obtained low levels of LTB4 in all the AIDS patients
      (mean 60.5 pg/ml), while the HIV negative subjects with degenerative and
      inflammatory pathologies of CNS showed a mean of 91.5 pg/ml. The finding of low
      levels of this inflammatory reaction mediator agrees with the limited clinical
      symptoms of cryptococcal meningoencephalitis in patients affected by AIDS.

PMID- 8735436
TI  - Annotation: behavioural phenotypes: a window onto the biology of behaviour.
AB  - Characteristic behavioural patterns (including cognitive processes and social
      interactions) have been reported in a number of syndromes arising from genetic or
      chromosomal abnormalities, suggesting that molecular analysis of the underlying
      defect could reveal the biological basis of the behavioural phenotype. Because of
      the rarity of many of the syndromes, and the complexity of their genetic basis,
      there are great difficulties in establishing the validity of the association
      between syndrome and behavioural phenotype. Nevertheless, evidence from animal
      studies with relevance to human behavioural phenotypes shows that the pathway
      from genotype to phenotype may be accessible by careful delineation of
      behavioural phenotypes.

PMID- 8735437
TI  - Rating child psychiatric caseness from detailed case histories.
AB  - Novel operationalized criteria were used to rate detailed psychiatric case
      histories on 151 schoolchildren with hemiplegia. Ratings of psychiatric caseness
      or non-caseness were reliable and valid; the method may be widely applicable.
      Caseness was defined both narrowly (in terms of social incapacity for the child)
      and broadly (in terms of disruption to others and distress too). Both definitions
      could be applied reliably to children of normal intelligence but broadly defined
      caseness was more reliable for children with low intelligence. Barely half of the
      psychiatric cases met operationalized criteria for one or more DSM-IV or ICD-10
      diagnosis. The others mostly had partial or mixed syndromes that could, with
      clinical judgement, be assigned to "not otherwise specified' diagnoses. Even with
      clinical judgement, however, a substantial minority of children with low
      intelligence had clinically significant but undiagnosable abnormalities in social
      relatedness.

PMID- 8735438
TI  - The Teddy Bears' Picnic : four-year-old children's personal constructs in
      relation to behavioural problems and to teacher global concern.
AB  - The study sought to establish cross-test validity for The Teddy Bears' Picnic
      (TBP), which assesses the internal personal constructs of the troubled child.
      After showing that the TBP could discriminate between 4-year-olds who were above
      and below cut-off on the Preschool Behaviour Checklist, the research demonstrated
      that both tests could distinguish levels of teacher concern about the behaviour
      and adjustment of the preschoolers in their care. When used in conjunction with
      one another, the two tests were more powerful than either used alone. The results
      suggested that children's internal perceptions of self and others, as revealed in
      pretense, are systematically related to their mental health status.

PMID- 8735439
TI  - Nonword repetition as a behavioural marker for inherited language impairment:
      evidence from a twin study.
AB  - The Children's Nonword Repetition Test (CNRep) was given 39 children with
      persistent language impairment (LI), 13 with a history of having received speech
      language therapy (resolved LI), and 79 controls, all aged from 7 to 9 years. The
      children with LI were twins who had participated in a previous genetic study.
      Children with resolved LI, as well as those with persistent LI, were
      significantly impaired on the CNRep. Comparisons of MZ and DZ twins indicated
      significant heritability of a CNRep deficit. It is concluded that CNRep provides
      a marker of the phenotype of heritable forms of developmental language
      impairment.

PMID- 8735440
TI  - Reading problems and antisocial behaviour: developmental trends in comorbidity.
AB  - Samples of poor and normal readers were followed through adolescence and into
      early adulthood to assess continuities in the comorbidity between reading
      difficulties and disruptive behaviour problems. Reading-disabled boys showed high
      rates of inattentiveness in middle childhood, but no excess of teacher-rated
      behaviour problems at age 14 and no elevated rates of aggression, antisocial
      personality disorder or officially recorded offending in early adulthood.
      Increased risks of juvenile offending among specifically retarded-reading boys
      seemed associated with poor school attendance, rather than reading difficulties
      per se. Reading problems were associated with some increases in disruptive
      behaviour in their teens in girls.

PMID- 8735441
TI  - An investigation of risk and protective factors in a sample of youthful
      offenders.
AB  - The study explored a set of potential risk and protective factors in relation to
      criminal activity and adjustment with a group of delinquent youths. The results
      indicated, first, that risk variables reflecting family relationship and
      parenting problems were associated with heightened rates of re-offending and
      lower overall adjustment. Second, the presence of protective factors relating to
      positive peer relations, good school achievement, positive response to authority
      and effective use of leisure time was associated with more positive outcomes with
      controls for the risk variables. Third, there was no evidence of interaction
      between risk and protective factors; the latter operated similarly at low and
      high levels of risk. These results are discussed in terms of their theoretical
      and applied significance.

PMID- 8735442
TI  - The genetics of children's oral reading performance.
AB  - Measures of reading achievement and verbal ability have been shown to be
      heritable. Additionally, recent evidence has been suggestive of a major gene
      effect on reading disability and for problem reading in a sample of normal
      readers. We report on the etiology of individual differences in oral reading
      performance, the Slosson Oral Reading Test (SORT), for which biometrical analyses
      have not been reported in the literature previously. Oral reading performance was
      measured in a large population-based sample of twins of the Virginia Twin Study
      of Adolescent Behavioral Development. Biometrical analyses of the SORT suggested
      that, in both males and females, 69% of the phenotypic variation was due to
      heritable influences and 13% of the variation due to shared environmental
      effects. While the relative importance of genetic and environmental influences is
      equivalent for males and females, males showed greater phenotypic variability
      than females.

PMID- 8735443
TI  - Disaster related stresses, depressive signs and symptoms, and suicidal ideation
      among a multi-racial/ethnic sample of adolescents: a longitudinal analysis.
AB  - Longitudinal findings are presented on the relationships between disaster related
      stresses, depression scores, and suicidal ideation among a multi-racial/ethnic
      sample of adolescents (N = 4,978) all of whom have been exposed to Hurricane
      Andrew. Regression analysis showed that being female, hurricane generated
      stresses, low levels of family support, pre-hurricane suicidal ideation, and post
      hurricane depression scores were significant predictors of post-hurricane
      suicidal ideation. Path analysis revealed that being female, low socioeconomic
      status, pre- and post-hurricane depression, high stress scores, low family
      support, and pre-hurricane suicidal ideation had significant direct/indirect
      effects on post-hurricane suicidal ideation.

PMID- 8735444
TI  - Fear, anxiety and perceived control in children of agoraphobic parents.
AB  - Sixteen children (M = 11 years) of agoraphobic parents were compared with 16
      children of parents with no history of psychopathology, matched on age, gender
      and socioeconomic status. The majority (68%) of children of agoraphobic parents
      met DSM-III-R diagnostic criteria, anxiety disorders being most common. They
      reported more fear and anxiety and less control over various risks than did
      comparison children. Group's perceptions of the prevalence and their
      vulnerability to these risks did not differ. Agoraphobic mothers reported more
      separation anxiety than did comparison mothers, and maternal separation anxiety
      was negatively correlated with children's perceived control. Results are related
      to models of anxiety transmission.

PMID- 8735445
TI  - Childcare patterns of mothers of twins during the first year.
AB  - This study aims to describe the ways in which mothers of twins organize their
      childcare activities during the first year after a twin birth and to determine
      what factors might affect these mothering practices. The mother's physical and
      psychological state, support and help from the father and others in the
      surroundings, and the type of twinship were among the factors studied. Data on
      the organization of feeding, sleeping and waking routines were gathered from 51
      families. A correspondence analysis and a cluster analysis showed that twin
      mothering practices can be described along two dimensions: individualized care vs
      collective care, and level of organization of daily routines. The mother's state
      of fatigue only partially accounts for the different types of maternal behavior.
      Likewise, the presence of several caregivers does not lead to greater
      individualization in care routines. Nor does there seem to be a clear link
      between the type of maternal behaviour and the type of twinship. The discussion
      deals with the mother's emotional investment, her personal capacity for adjusting
      to the "triadic motherhood' process, and the nature of the father's involvement
      in that process. Another consideration is the impact of the type of childcare
      pattern on twin development.

PMID- 8735446
TI  - Long-term stability of individual differences in the emotional responsiveness of
      children with autism.
AB  - The results of two studies designed to investigate the short- and long-term
      stability of autistic children's responsiveness to displays of negative emotions
      in others are reported here. In the first study we measured the attention and
      behavioural responses of 22 autistic children to another's distress about a year
      and a half after initial assessments in a similar situation. In the second study,
      the children were re-assessed in two affective contexts over 5 years after
      initial testing. Individual differences in early responses to affect predicted
      affective responsiveness at each follow-up. Emotional responsiveness was
      positively associated with concurrent cognitive skills at each point of
      assessment. Furthermore, autistic children discriminated between affective and
      non-affective contexts when this discrimination was tested at the second follow
      up.

PMID- 8735447
TI  - Life event precipitants of adolescent anorexia nervosa.
AB  - As part of a prospective outcome study, independent life events occurring in the
      year before onset in 35 consecutive cases of anorexia nervosa were recorded by a
      semi-structured interview with the subject and a parent. Negative impact and
      context were rated blind, using the case vignette method. Subjects with anorexia
      reported intermediate rates of negative life events between community and
      psychiatric controls. Chronic adversities were common. Negative life events were
      associated with depressive disorder in controls, but not in those with anorexia.
      Significant under-reporting of events may occur in this population.

PMID- 8735448
TI  - Theory of mind and rule use in individuals with Down's syndrome: a test of the
      uniqueness and specificity claims.
AB  - The relationship between Theory of Mind (ToM) and rule use was explored in adults
      with Down's Syndrome (DS) and in non-handicapped pre-schoolers. Twelve low
      functioning individuals with DS (mean mental age = 5.1 years, mean chronological
      age = 22.7) performed worse than 12 MA-matched non-handicapped children (mean MA
      = 5.1 years) on several standard ToM tasks and on a color-shape card-sorting task
      in which subjects were required to switch between two incompatible sets of rules.
      On the ToM tasks, people with DS tended to focus on a single state of affairs
      (e.g. the present situation). Likewise, on the card sort, these subjects tended
      to use a single set of rules on all trials. Performance in the two types of task
      was positively correlated when MA was partialed out. The results are inconsistent
      with the slaim that ToM reflects a domain-specific psychological function and the
      notion that deficits in ToM are unique to individuals with autism.

PMID- 8735449
TI  - The antimicrobial properties of chile peppers (Capsicum species) and their uses
      in Mayan medicine.
AB  - A survey of the Mayan pharmacopoeia revealed that tissues of Capsicum species
      (Solanaceae) are included in a number of herbal remedies for a variety of
      ailments of probable microbial origin. Using a filter disk assay, plain and
      heated aqueous extracts from fresh Capsicum annuum, Capsicum baccatum, Capsicum
      chinese, Capsicum frutescens, and Capsicum pubescens varieties were tested for
      their antimicrobial effects with fifteen bacterial species and one yeast species.
      Two pungent compounds found in Capsicum species (capsaicin and dihydrocapsaicin)
      were also tested for their anti-microbial effects. The plain and heated extracts
      were found to exhibit varying degrees of inhibition against Bacillus cereus,
      Bacillus subtilis, Clostridium sporogenes, Clostridium tetani, and Streptococcus
      pyogenes.

PMID- 8735450
TI  - Effects of Hemerocallis flava on motor activity and the concentration of central
      monoamines and its metabolites in rats.
AB  - In this study, we used behavioral and biochemical methods to investigate the
      effects of Hemerocallis flava (Liliaceae) (abbreviated as HF) on motor activity
      and the concentration of monoamines in rats. The water fraction of the
      resuspended HF extract was most active in reducing the motility in rats. The
      water fraction of the HF extract enhanced the reduction of locomotor activity
      produced by alpha-methyl-p-tyrosine and 5-hydroxytryptophan, but it reduced the
      increase of locomotor activity produced by L-dopa plus benserazide and p
      chlorophenylalanine. Furthermore, the water fraction of the HF extract
      significantly decreased the concentration of norepinepherine in the cortex and
      the concentration of dopamine and serotonin in the brain stem. It also increased
      the concentration of vanilylmandelic acid in the cortex, homovanillic acid and 5
      hydroxyindole-acetic acid in the brain stem. These results suggest that the
      reduction of locomotor activity produced by the water fraction of HF extract may
      be related to the decrease in the concentration of norepinepherine in the cortex
      and the concentration of dopamine and serotonin in brain stem.

PMID- 8735451
TI  - Effects of an ethanolic extract of Desmodium adscendens on central nervous system
      in rodents.
AB  - This study investigates some pharmacological effects of the ethanolic extract of
      the leaves of Desmodium adscendens (Papillionaceae), a medicinal plant in the
      African traditional medicine, on the central nervous system. The plant extract
      induced hypothermia and had analgesic effect in mice. D. adscendens suppressed
      the tonic phase of convulsion and mortality induced by pentylenetetrazole (PTZ)
      in mice. In addition, the plant extract delayed the onset of PTZ forelimb clonus,
      and generalized limbic seizures induced by kainic acid. In contrast, the plant
      extract did not affect either tonic convulsion induced by maximal electroshock in
      mice or the progression of limbic seizures towards the status epilepticus in
      rats.

PMID- 8735452
TI  - Carrier herbal medicine: traditional and contemporary plant use.
AB  - The Carrier, an Athapaskan-speaking people of northcentral British Columbia,
      occupy the sub-boreal spruce forests of the central interior. This report, which
      is based on field study, documents some traditional and contemporary knowledge of
      the medicinal use of plants by the Carrier people. Important medicinal plants
      include: Abies lasiocarpa, Alnus incana, Arctostaphylos uva-ursi, Artemisia
      frigida, Fragaria virginiana, Juniperus communis, Picea glauca, Pinus contorta,
      Populus tremuloides, Rubus idaeus and Shepherdia canadensis.

PMID- 8735454
TI  - Diuretic and natriuretic effects of chromatographically purified fraction of
      garlic (Allium sativum).
AB  - The intravenous administration of chromatographically purified fractions of
      garlic (2, 4 and 6 micrograms/kg dry weight) to anaesthetized rabbits elicits
      dose-dependent diuretic-natriuretic responses which reach a maximum 60 min after
      injection, and return to basal levels after 90 min. A gradual decrease in heart
      rate, but not in arterial blood pressure was observed during the course of the
      experimental periods. The electrocardiogram was not affected.

PMID- 8735453
TI  - Screening of Zulu medicinal plants for prostaglandin-synthesis inhibitors.
AB  - Aqueous and ethanolic extracts of 39 plants used in traditional Zulu medicine to
      treat headache or inflammatory diseases were screened for prostaglandin-synthesis
      inhibitors. Extracts were tested in an in vitro assay for cyclooxygenase
      inhibitors. In general, ethanolic extracts caused higher inhibition than aqueous
      extracts. Two-thirds of the plants screened had high inhibitory activity. The
      highest inhibition was obtained with ethanolic extracts of Bidens pilosa, Eucomis
      autumnalis, Harpephyllum caffrum, Helichrysum nudifolium, Leonotis intermedia, L.
      leonorus, Ocotea bullata, Rumex saggitatus, Solanum mauritianum, Synadenium
      cupulare and Trichilia dregeana.

PMID- 8735455
TI  - Hepatoprotective effects of emodin from Ventilago leiocarpa.
AB  - A major component of ethyl acetate (EtOAc) and chloroform (CHCl3) fractions of
      Ventilago leiocarpa Bunge (Rhamnaceae), emodin, was isolated and exhibited
      hepatoprotective effects on carbon tetrachloride (CCl4) as well as D
      galactosamine (D-GalN)-induced liver damage. The histopathological examination
      also clearly showed that emodin reduced lymphocyte cells, Kupffer cells,
      ballooning degeneration, cell necrosis and hyaline degeneration on CCl4 and D
      galactosamine-induced tests.

PMID- 8735456
TI  - Protection of mouse bone marrow by Si-WU-Tang against whole body irradiation.
AB  - The ability of Si-Wu-Tang to eliminate bone marrow damage after radiation was
      assessed using both a clonogenic assay (survival of colony forming units spleen-
      CFUs) of stem cell survival and a hematopoietic functional assay including the
      changes of hemograms and hematocrit. Cell survival curves and dose-response
      curves for radiation alone and Si-Wu-Tang administration with radiation were
      constructed over the dose range of 1 to 9 Gy. Si-Wu-Tang was given 7 days before
      irradiation at a consecutive fractionated dose of 20 mg/20 g body weight. The
      radioresistance of stem cells treated by Si-Wu-Tang was higher than that of those
      treated by irradiation alone. However, the anti-radiation effect of leukocytes
      was not as significant as that of erythrocytes, thrombocytes and hematocrit.
      These data suggest that the anti-radiation effect by Si-Wu-Tang is dependent on
      dose and will be less after 4 Gy irradiation. Hemograms with a short turnover
      period, such as leukocytes, may be less affected after Si-Wu-Tang administration.

PMID- 8735457
TI  - Antimicrobial activity of Paliurus spina-christi Mill. (Christ's thorn).

PMID- 8735458
TI  - Single fibre electromyographic changes in man after organophosphate exposure.
AB  - 1. Neuromuscular (NM) changes resulting from organophosphate exposure are known
      to be complex. After severe acute poisoning recovery from initial depolarisation
      paralysis may be followed in a limited number of cases by onset of a non
      depolarisation paralysis (the Intermediate Syndrome). It is not clear whether
      this block arises subclinically in all cases of poisoning as a sequel to the
      initial depolarisation. 2. Single fibre electromyography (SFEMG) is a sensitive
      clinical neurophysiological technique allowing detection of subclinical changes
      at the neuromuscular junction. In the study reported it has been used to examine
      changes in NM transmission in the forearm of fit volunteers exposed to a low
      level of sarin (isopropyl methyl phosphonofluoridate). 3. Small changes in SFEMG
      were seen at three hours and three days after an exposure sufficient to cause a
      reduction in red cell acetyl cholinesterase to 60% of normal. The SFEMG changes
      were not accompanied by any clinical neuromuscular symptoms or signs and returned
      to normal 2 years after exposure. 4. The results indicate that there are
      reversible subclinical changes compatible with the development of non
      depolarising NM block without frank clinical expression. In the small population
      examined there were individual variations in response which may reflect
      differences in safety margin at the neuromuscular junction.

PMID- 8735459
TI  - Evolution of lead toxicity in a population of children.
AB  - A 3 years study was conducted to determine the evolution of blood lead
      concentrations (PbB) and free erythrocyte protoporphyrins (FEP) as indicators of
      absorption and biochemical damage in children (7-12 years old) living within one
      kilometer of a metallurgic factory that processes lead in Torreon, Coahuila,
      Mexico. In addition, neuromuscular conduction velocity, motor coordination and IQ
      where determined as indicators of physiological damage. During this period of
      time the children showed increased lead blood concentrations of 19.2 +/- 4.5
      micrograms dl-1 at the beginning of the study to 27.5 +/- 4.9 micrograms dl-1 at
      the end. Likewise, FEP increased from 56.6 +/- 20.0 micrograms dl-1 to 92.9 +/-
      28.9 micrograms dl-1. Physiological damage was evident since motor coefficients
      as well as IQ tests were reduced significantly when compared to children (7-12
      years old) living 4.5 km away from the factory who showed PbB = 8.9 +/- 1.3
      micrograms dl-1 and FEP = 16.9 +/- 4.7 micrograms dl-1 throughout the study.
      Based on these data it was possible to define three different groups with regards
      to lead toxicity sensitivity.

PMID- 8735460
TI  - The influence of pharmacological pretreatment on efficacy of HI-6 oxime in
      combination with benactyzine in soman poisoning in rats.
AB  - 1. The influence of pharmacological pretreatment (pyridostigmine, benactyzine and
      trihexyphenidyle), designated PANPAL, on soman-induced cholinergic and
      stressogenic effects as well as on the efficacy of antidotal treatment (HI-6 plus
      obidoxime) in rats was studied. 2. PANPAL prophylaxis significantly decreased
      soman-induced cholinesterase inhibition in blood, brain and diaphragm as well as
      stressogenic effects of soman (an increase in plasma corticosterone level and
      liver tyrosine aminotransferase activity). 3. PANPAL pretreatment did not improve
      the efficacy of HI-6 in combination with benactyzine on soman-induced
      anticholinesterase and stressogenic effects. 4. These findings confirm that
      PANPAL prophylaxis can improve prognosis of soman poisoning especially by
      protection of cholinesterases.

PMID- 8735461
TI  - A systemic reaction following exposure to a pyrethroid insecticide.
AB  - The pyrethroids are a group of pesticides in wide use around the world. They are
      felt to be safer than the organophosphates. We report a case of an acute systemic
      reaction in a farmer following exposure to the synthetic pyrethroid flumethrine.

PMID- 8735462
TI  - Influence of cimetidine on the toxicity and toxicokinetics of diazinon in the
      rat.
AB  - 1. The influence of cimetidine on diazinon toxicity and toxicokinetics was
      investigated in male Wistar rats. 2. The acute toxicity of diazinon, as well as
      brain acetylcholinesterase and carboxylesterase inhibition, were potentiated by
      pretreating rats with cimetidine (80 mg kg-1, i.p.) 1 and 24 h prior to diazinon
      application (50 mg kg-1, i.p.). 3. Comparison of toxicokinetic parameters between
      control and cimetidine-treated animals, showed a significant decrease in diazinon
      total body clearance and a marked increase in the area under the plasma
      concentration-time curve following cimetidine. 4. These results indicate that a
      major cause of the potentiation of diazinon may be related to the increase in the
      amount of diazinon in the systemic circulation as well as in the brain.

PMID- 8735463
TI  - Dermal absorption of cis-1,3-dichloropropene vapour: human experimental exposure.
AB  - 1. The relevance of skin absorption of cis-1,3-dichloropropene (cis-1,3-DCP)
      vapour as a route of entry compared to inhalatory uptake has been assessed in
      human volunteers under controlled exposure conditions. 2. Five adults (four males
      and one female) were dermally exposed on the forearm and hand during 45 min to 86
      mg/m3 cis-1,3-DCP. 3. Dermal uptake was assessed by determination of the main cis
      1,3-DCP metabolite in urine: the mercapturic acid conjugate of cis-1,3-DCP (cis
      1,3-DCP-MA). 4. When whole-body dermal exposure to vapour is compared to
      inhalatory exposure, the uptake through the skin is estimated to be about 2-5% of
      the inhalatory absorption.

PMID- 8735464
TI  - Cadmium-induced alterations in blood-brain barrier permeability and its possible
      correlation with decreased microvessel antioxidant potential in rat.
AB  - 1. Male albino rats of 21 days age were exposed to 10 p.p.m. cadmium (CdCl2 salt)
      in drinking water, ad libitum, for 90 days. It increased the brain cadmium levels
      by 76% (P < 0.05) and 165% (P < 0.001) respectively at 30 and 90 days of exposure
      compared to controls. 2. Cadmium increased blood-brain barrier permeability of
      fluoroscein dye (24%, P < 0.02) and the levels of brain microvessel
      malondialdehyde (31%, P < 0.01) at 90 days of exposure. However, these parameters
      did not alter significantly at 30 days of exposure. 3. Increased activities of
      microvessel superoxide dismutase (18%, P < 0.02), glutathione peroxidase (20%, P
      < 0.01) and catalase (28%, P < 0.01) were observed at 30 days of exposure. 4. The
      continuation of the Cd treatment for 90 days decreased the levels of superoxide
      dismutase (30%, P < 0.001), glutathione peroxidase (23%, P < 0.005), catalase
      (25%, P < 0.005), glutathione reductase (18%, P < 0.02), vitamin E (20%, P <
      0.01), glutathione (26%, P < 0.01), ascorbic acid (18%, P < 0.05) and
      ceruloplasmin (13%, P < 0.05) in the microvessal preparation compared to
      controls. 5. It appears that Cd-induced blood-brain barrier dysfunction may be
      related to the depletion of microvessel antioxidant substances along with
      increase in lipid peroxidation at 90 days of exposure.

PMID- 8735465
TI  - Reproductive toxicity and tissue concentrations of lindane in adult male rats.
AB  - 1. The effects of lindane on the reproductive system and its concentration in
      different tissues were investigated. Groups were dosed orally with 6 mg
      lindane/kg for 5 days or with a single dose of 30 mg/kg body weight. 2. The
      results indicate that the number (mio) of spermatids counted in the testes of
      both treated groups 2 weeks after treatment were significantly reduced compared
      to the control rats. Effects on the number of sperms were observed in both
      treated groups, but significant differences were only revealed on those with 30
      mg/kg. 3. The concentration (microgram/g tissue) of lindane in adipose tissue,
      liver, brain and testis was determined 24 h and 2 weeks after the last treatment.
      Lindane was detected in the testis of both groups 24 h and 2 weeks after the last
      treatment. 4. Histological investigation by electron microscopy revealed a
      pronounced ballooning of Sertoli cells accompanied by fragmentation or complete
      loss of organelles. 5. According to the result obtained, it is evident that
      lindane passes through the testis and exerts its toxic effect.

PMID- 8735466
TI  - Experimental study of the detrimental effect of dopamine/glucagon combination in
      d,l-propranolol intoxication.
AB  - 1. Respiratory and cardiovascular failure are the principle toxic effects of beta
      blocker overdose. Respiratory arrest is the primary cause of death in beta
      blocker intoxicated rats. 2. The effect of glucagon, dopamine and the combination
      of glucagon/dopamine on respiratory and cardiovascular function and survival time
      in beta-blocker overdose was investigated in a model of acute d,l-propranolol
      (resp. 30 and 15 mg kg-1 h-1 in rat and rabbit) intoxication in spontaneously
      breathing rats and artificially ventilated rats and rabbits. 3. Glucagon (initial
      dose of 100 micrograms kg-1 (bolus), followed by 1 microgram kg-1 min-1),
      dopamine (25 micrograms kg-1 min-1) or the combination of glucagon/dopamine did
      not improve survival time (ST) in d,l-propranolol intoxicated spontaneously
      breathing rats and artificially ventilated rats and rabbits, although some
      haemodynamic variables i.e. heart rate (HR), mean arterial blood pressure (MAP),
      left ventricular pressure (LVPmax) and the differentiated left ventricular
      pressure (LVdp/dtmax) temporarily improved. 4. Survival time was considerably
      reduced in d,l-propranolol intoxicated spontaneously breathing and artificially
      ventilated rats treated with a combination of glucagon/dopamine, which induced a
      decrease in PaO2 and pH and an increase in PaCO2 partly due to
      ventilation/perfusion mismatch. 5. The combination of glucagon/dopamine should be
      used carefully in the treatment of beta-blocker overdose in man.

PMID- 8735467
TI  - Benzene metabolites enhance reactive oxygen species generation in HL60 human
      leukemia cells.
AB  - Benzene is myelotoxic and leukemogenic in humans. The mechanisms leading to these
      effects, however have not been fully elucidated. One of the underlying mechanisms
      is believed to be the oxidative damage caused by its metabolites. A comparative
      study was undertaken to examine the relationships between reactive oxygen species
      (ROS) production, lipid peroxidation and subsequent cytotoxicity induced by five
      major benzene metabolites. The generation of ROS by benzene metabolites was
      demonstrated by the significant and dose-dependent increase of intracellular ROS
      formation in HL60 human promyelocytic leukemia cells in vitro. 1,4-Benzoquinone
      (BQ) was found to be the most potent metabolite in induction of ROS formation,
      followed by 1,2,4-benzenetriol (BT) and to a lesser extent, phenol (PH) and
      trans, trans-muconaldehyde (MD). No significant effect was observed when the
      cells were treated with trans, trans-muconic acid (MA). The enhancement of ROS
      production by BQ was effectively inhibited by the addition of catalase,
      deferoxamine (DFO) and dimethyl sulfoxide (DMSO), but unchanged by superoxide
      dismutase (SOD), suggest that hydrogen peroxide (H2O2) and hydroxyl radicals (OH)
      are the two major forms of ROS involved. The results also demonstrate that the
      ability of benzene metabolites in enhancing ROS generation is closely correlated
      to their capacity in causing lipid peroxidation and subsequent cytotoxicity.
      These findings together with earlier parallel observations on DNA damage suggest
      that ROS play an important role in the mechanism of carcinogenesis induced by
      benzene metabolites.

PMID- 8735468
TI  - Mitigation of nitrofurantoin-induced toxicity in the perfused rat liver.
AB  - 1. Nitrofurantoin is an antimicrobial agent which produces hepatotoxicity caused
      by the redox cycling of the nitro group and its radical anion. This futile
      cycling triggers a complex series of events known collectively as oxidative
      stress. 2. Our goal was to determine treatment strategies which could mitigate
      nitrofurantoin-induced toxicity in the isolated perfused rat liver. We co-infused
      various agents which blocked early or late events in the progression to toxicity.
      Tissue levels of glutathione and protein thiols were measured as indicators of
      the progression to toxicity and lactate dehydrogenase leakage into the perfusate
      was used as a marker of irreversible cell death. 3. Five treatments significantly
      (P < 0.05) decreased LDH leakage (reported as thousands of units accumulated in
      perfusate at 300 min, mean+/-standard error, n = 3-4) when compared to
      nitrofurantoin alone (274 +/- 37). These treatments were adenosine-2'
      monophosphate (120 +/- 53), penicillamine (90 +/- 29), N-(2-mercaptopropionyl)
      glycine (120 +/- 49) and bromosulfophthalein with (80 +/- 29) or without 5,5'
      difluro-1,2-bis(O-aminophenoxy)ethane-N,N,N'N'-tetraace tic acid (101 +/- 46).
      Two other treatments, N-acetylcysteine (183 +/- 7) and dithiothreitol (166 +/-
      59) delayed the onset of toxicity. Finally, calpeptin (319 +/- 34) which blocks
      activation of nonlysosomal proteases was ineffective. 4. We concluded that early
      intervention on the pathway to toxicity was most effective. The strategies
      detailed here may prove beneficial in treating hepatotoxicity seen following
      nitrofurantoin therapy.

PMID- 8735470
TI  - Morphology of ricin and abrin exposed endothelial cells is consistent with
      apoptotic cell death.
AB  - Cultures of bovine pulmonary endothelial (BPE) cells were exposed to LC70 doses
      of ricin or abrin (15.5 and 4.5 pM respectively) over a period of up to 40 h. The
      viability of the cultures (as determined by the neutral red (NR) dye retention
      assay) declined after 6 h exposure to the toxins. From 15 h onwards, cellular
      material in toxin exposed cultures became detached from the substratum of the
      culture vessels. Hoffman modulation contrast photomicrography showed that this
      process was due to ricin and abrin exposed cells collapsing into membrane bound
      vesicles which retained the NR dye, became detached and floated into the medium.
      These apoptotic-like structural changes were further investigated by transmission
      electron microscopy (TEM) and by agarose gel electrophoresis of DNA from control
      and exposed cultures. Many of the characteristic changes associated with
      apoptotic cell death were seen using TEM, including heterochromatin condensation
      at the nuclear periphery, crenulation of the nuclear membrane and progressive
      degeneration of residual nuclear and cytoplasmic structures. The plasma membrane
      of many cells remained intact, and contained nuclear and cytoplasmic debris.
      Agarose gel electrophoresis of DNA extracted from toxin-treated cells revealed
      oligonucleosome sized DNA fragments, characteristic of apoptosis, from adherent
      cells at 7 h and both adherent and floating populations when harvested from 15 h;
      DNA from unexposed control cells did not show this fragmentation. The
      identification of apoptosis as being a significant additional mechanism of
      toxicity following exposure to ricin and abrin holotoxins raises the possibility
      of developing new therapeutic strategies against poisoning by these phytotoxins.

PMID- 8735469
TI  - CYP enzymes catalyze the formation of a terminal olefin from 2-ethylhexanoic acid
      in rat and human liver.
AB  - 1. The metabolism of 2-ethylhexanoic acid (2-EHA) was studied in rat, mouse and
      human liver microsomes in vitro. The metabolites of 2-EHA were identified as
      methylated derivatives by gas chromatography-mass spectrometry. 2. 2-Ethyl-1,6
      hexanedioic acid was the main metabolite produced in rat, mouse and human liver
      microsomes. Unsaturated 2-ethyl-5-hexenoic acid, a terminal olefin, was produced
      only in human liver microsomes and phenobarbital-induced rat liver microsomes.
      The cytochrome P450 (CYP) inhibitors metyrapone, SKF 525A, triacetyloleandomycin
      (TAO), quinidine and the cytochrome P450 reductase antibody abolished its
      formation both in rat and human microsomes. 3. The metabolites were analyzed also
      in vivo in urine of 2-EHA-exposed rats and in urine of sawmill workers exposed
      occupationally to 2-EHA. Both rat and human urine contained 2-ethyl-1,6
      hexanedioic acid as the main metabolite and also 2-ethyl-5-hexenoic acid.
      Metyrapone, SKF 525A and TAO all decreased drastically the formation of 2-ethyl-5
      hexenoic acid in the rat. 4. The data indicate that (1) several CYP families
      (CYP2A, CYP2B, CYP2D and CYP3A) could be responsible for the hepatic metabolism
      of 2-EHA, (2) the same metabolites were formed in rats and man and (3) an
      unsaturated terminal olefin, 2-ethyl-5-hexenoic acid is formed in the liver.

PMID- 8735471
TI  - Report of the meeting on 'animal welfare in regulatory toxicology' under the
      auspices of the British Toxicology Society, 27 April 1995.

PMID- 8735472
TI  - Innate defect? Bronchial epithelial cells of atopic patients with asthma lack the
      ability to activate allergens.

PMID- 8735473
TI  - Adam and Eve make love. Analysis of the enantiomers of 3,4-methylenedioxy-N
      ethylamphetamine (MDE, "Eve") and its metabolite 3,4-methylenedioxyamphetamine
      (MDA) in rat brain.

PMID- 8735474
TI  - TUNEL--morituri te salutant. Quantitative in situ image analysis of apoptosis in
      well and poorly differentiated tumors from rat liver.

PMID- 8735475
TI  - Intracavitary systems.

PMID- 8735476
TI  - Increased morbidity following the introduction of remote afterloading, with
      increased dose rate, for cancer of the cervix.
AB  - A retrospective review of the treatment of cancer of the cervix compared the 3
      year period before and after the introduction of remote afterloading using a "low
      dose rate' Selectron. Data was collected on 270 patients. Compared to manually
      loaded caesium the dose rate to point A was doubled with Selectron and a dose
      reduction of 20% was adopted to compensate for the expected increased
      effectiveness. The combined grade 2 and 3 complication rates were 12% with
      manually loaded caesium and 32% with Selectron at the higher dose rate. Survival
      and local control rates were similar.

PMID- 8735477
TI  - Massive haemoptysis death and other morbidity associated with high dose rate
      intraluminal radiotherapy for carcinoma of the bronchus.
AB  - Four hundred and six patients with primary non-small cell carcinoma of the
      bronchus causing symptoms due to endobronchial disease, were treated with
      intraluminal radiotherapy (ILT) using the microSelectron-HDR machine at the
      Christie Hospital, Manchester, between April 1988 and the end of 1992. An
      assessment of morbidity for this treatment is presented, particularly with regard
      to the risk factors and causes of massive haemoptysis death. The most common
      early side-effect was a mild transient exacerbation of cough which usually
      resolved within 2-3 weeks. At various times following ILT treatment 83
      bronchoscopies were carried out randomly in 55 patients. In bronchoscopies
      carried out within the first 3 months following ILT, no tumour was visible in 80%
      of cases. A mucosal radiation reaction score (RRS) was used to grade
      bronchoscopic appearance after ILT treatment. Overall, 55% of bronchoscopic
      examinations showed some degree of mucosal radiation reaction. The majority of
      radiation reactions from 6 months onwards after ILT demonstrated a degree of
      fibrosis. A radiation reaction was seen more frequently after treatment with 2000
      cGy as opposed to 1500 cGy at 1 cm from the central axis of the radiation source.
      Thirty-two patients were identified who had died from massive haemoptysis (MH) as
      a terminal event. A Cox multivariate regression analysis showed that the
      treatment-related factors of increased dose at first ILT (P = 0.004), prior laser
      treatment at the site of ILT (P = 0.020) and second ILT treatment in the same
      location as the first ILT treatment (P = 0.047), all significantly increased the
      relative risk of MH death compared with their effect on the relative risk of
      death from other causes (OC). (In addition a fourth treatment-related factor,
      namely the concurrent use of ILT and external beam radiotherapy (EB) had a P
      value of 0.08). Twenty out of 25 assessable MH-death patients (80%) had evidence
      of recurrent or residual tumour before death but 5 patients (20%) did not. For
      surviving patients the instantancious risk of death at any one time (the cause
      specific death rate expressed as deaths per 100 cases per month), showed a sharp
      peak for MH deaths between 9 and 12 months post ILT in contradistinction to OC
      death where the peak was between 3 and 6 months post ILT. These findings may
      imply a role for late radiation reaction in the treatment-related risk factors
      identified as increasing the relative risk of MH death and possible mechanisms
      are discussed. The results have implications for treatment regimes that use a
      dose of 2000 cGy at 1 cm in a single fraction technique, that have a high
      frequency of previous laser treatment, that use multiple, repeated ILT treatments
      in the same location and that use ILT concurrently with EB.

PMID- 8735478
TI  - Replacement of hairpin and loop implants by optimised straight line sources.
AB  - Remote after loading is desirable for all forms of brachytherapy but is difficult
      in the oral cavity because the tight curvature at the top of implanted loops
      impedes passage of the source. For this reason we investigated differential
      loading of straight catheters to simulate a conventional loop or hairpin. Using a
      pulsed brachytherapy remote after loader the top four dwell positions of straight
      catheters were given two to four times the dwell time of other source positions.
      This raised the reference isodose to cover the surface mucosa without
      significantly changing either the total volume treated or the volume receiving >
      150% of reference dose when compared with conventional loop implants of
      equivalent source length and separation. This optimised straight line implant
      should therefore be amenable to remote afterloading and have similar dose/volume
      characteristics to loops.

PMID- 8735479
TI  - Influence of respiration on calculation and delivery of the prescribed dose in
      external radiotherapy.
AB  - During the delivery of the prescribed dose in external beam radiotherapy,
      respiration alters the patient's body outline and consequently the basis for dose
      calculations. The influence of this effect was studied on both healthy volunteers
      and patients. In a subgroup of volunteers, we measured that respiratory movements
      modify a person's thickness, in particular in the antero-posterior direction at
      the lower abdominal level, by more than 4% implying a variation in absorbed dose
      of more than 2%. In view of the I.C.R.U. requirements for absorbed dose accuracy,
      these variations must be taken into account. Extension of the study to a group of
      160 patients confirmed that for a subgroup of about 25%, respiration induces an
      important deviation from the prescribed dose as dose calculations are based on a
      body outline taken at an unknown stage during the respiratory cycle. Our results
      indicate that dose calculations should be based on an average body outline which
      takes the respiratory movements into account.

PMID- 8735480
TI  - Comparison of two techniques for detecting tumour hypoxia: a fluorescent
      immunochemical method and an in vitro colony assay.
AB  - The aim of this study was to compare the percentage of hypoxic cells obtained
      with two methods: an in vitro colony assay and a new method based on
      immunodetection of a marker for hypoxic cells (NITP) which could be used in
      patients. These studies have been carried out using one rodent tumour EMT6 (a
      mammary carcinoma) and one human tumour HRT18 (a rectal adenocarcinoma). The
      hypoxic cell fraction was assessed in control mice and in mice receiving two
      treatments: 250 mg/kg nicotinamide + carbogen, and 250 mg/kg nicotinamide +
      carbogen + 4 ml/kg perflubron emulsion. The two treatments increased the
      radiosensitivity of the two cell lines, nicotinamide plus carbogen plus
      perflubron emulsion having the greatest radiosensitising effect. For untreated
      and treated tumours, the percentage of hypoxic cells obtained with the in vitro
      colony assay were comparable to those obtained with immunodetection using NITP.
      Whatever the treatment, NITP detection was a convenient test to detect the
      hypoxic cell fraction in the two solid tumours we have studied.

PMID- 8735481
TI  - Repopulation in the SCCVII squamous cell carcinoma assessed by an in vivo-in
      vitro excision assay.
AB  - An in vivo-in vitro excision assay was used to study repopulation after a single
      dose of clamped irradiation (40 Gy) in the SCCVII tumour implanted in the foot of
      C3H/Km mice. The growth pattern of clonogenic cells was analysed by two different
      mathematical models: the logistic model and the Gompertz model. The logistic
      model described the data better than the Gompertz model. Accelerated repopulation
      was found when the regrowth rate after irradiation was compared to the growth
      rate at the time of treatment, and when it was compared to the growth rate in
      untreated tumours with a number of cells equivalent to the number that was found
      after irradiation. The clonogenic doubling time (cDT) was estimated at 15.1 h
      (95% c.i.: 14.2; 16.0) after irradiation, and 27.8 h (95% c.i.: 16.7; 43.5) in
      untreated controls of matching size. However, the estimate relies on the
      mathematical model chosen and on extrapolation below actually measured data. A
      small cDT points to shortening of the cell cycle time and recruitment of non
      cycling clonogenic tumour cells to be the main mechanism behind the accelerated
      repopulation.

PMID- 8735482
TI  - Intratumoral heterogeneity as a confounding factor in clonogenic assays for
      tumour radioresponsiveness.
AB  - The level of intra-tumoral heterogeneity of cellular radiosensitivity within
      primary cultures of three carcinomas of the cervix has been established. All
      three cultures contained clones that varied by as much as 3-fold in their
      clinically relevant radiosensitivity (SF2). The level of intra-tumoral
      heterogeneity observed in these cervical tumour cultures was sufficient to be a
      major confounding factor to the use of pre-treatment assessments of
      radiosensitivity to predict for clinical radioresponsiveness. Mathematical
      modeling of the relative elimination of the tumour clones during fractionated
      radiotherapy indicates that, in two of the three biopsy samples, the use of pre
      treatment derived SF2 values from the heterogeneous tumour sample would
      significantly overestimate radioresponsiveness. We conclude that assays of
      cellular radiosensitivity that identify the radiosensitivity of the most
      radioresistant clones and measure their relative abundance could potentially
      increase the effectiveness of SF2 values as a predictive marker of
      radioresponsiveness.

PMID- 8735483
TI  - Relationship between DNA damage, rejoining and cell killing by radiation in
      mammalian cells.
AB  - The prevailing hypothesis on the mechanism of radiation-induced cell killing
      identifies the genetic material deoxyribonucleic acid (DNA) as the most important
      subcellular target at biologically relevant doses. In this review we present new
      data and summarize the role of the DNA double-strand breaks (dsb) induced by
      ionizing radiation and DNA dsb rejoining as determinants of cellular
      radiosensitivity. When cells were irradiated at high dose-rate, two molecular end
      points were identified which often correlated with radiosensitivity: (1) the
      apparent number of DNA dsb induced per Gy per DNA unit and (2) the half-time of
      the fast component of the DNA dsb rejoining kinetics. These two molecular
      determinants, not mutually exclusive, may be linked through a common factor such
      as the conformation of DNA.

PMID- 8735484
TI  - Early inflammatory reaction of the rabbit coeliac artery wall after combined
      intraoperative (IORT) and external (ERT) irradiation.
AB  - The present immunohistochemical study of radiation-induced damage in major blood
      vessels is based on a multidisciplinary study (Schultz-Hector et al., Radiother.
      Oncol., 38: 205-214, 1996) investigating the combined effect of IORT of the
      coeliac axis and upper abdominal ERT. The paper describes the sequential changes
      occurring in the coeliac artery after IORT with 30 Gy, i.e. during and after
      combined IORT and fractionated ERT (total dose 40 Gy). Within 24 h after IORT,
      the arterial wall was found to be invaded by TNF-alpha positive macrophages,
      which later on disappeared within 7-14 days. At 2 days post-IORT, the medical
      smooth muscle cells were strongly positive for TNF-alpha and remained positive
      throughout the observation period of 63 days. At 80 days, a comparison of
      different IORT dose groups showed that TNF-alpha expression after 20 and 30 Gy
      IORT plus 40 Gy ERT had subsided, while it was still strongly evident after 40 Gy
      IORT. Negative reactions in sham irradiated animals or animals treated with ERT
      alone indicate that TNF-alpha expression was caused by IORT. After > 30 days post
      IORT, there was increased collagen type I deposition in the adventitia. In two
      animals receiving the full ERT course, intimal proliferations involving mainly
      smooth muscle cells were observed. Our findings indicate that some features
      typical of radiation induced arteriosclerosis such as periarterial fibrosis and
      intimal proliferations can occur as early as < 60 days postirradiation.
      Macrophage invasion as well as TNF-alpha expression in medial smooth muscle cells
      are known to be important steps in the development of spontaneous atherosclerotic
      lesions. Therefore, early TNF-alpha induction in the arterial wall by a high
      local dose of X-irradiation may be regarded as one initiating factor of chronic
      radiation-induced arteriosclerosis.

PMID- 8735485
TI  - Intratumoral radioimmunotherapy of a human colon cancer xenograft using a
      sustained-release gel.
AB  - Low tumor uptake and normal tissue toxicity limit the efficacy of RIT for the
      treatment of solid tumors. In this study, an intratumoral injectable gel drug
      delivery system for local administration of RIT was evaluated using the LS174T
      human colon cancer xenograft model in SCID mice. The injectable gel is a collagen
      based drug delivery system designed for intratumoral (i.t.) administration, which
      has previously been shown to enhance drug retention at the injection site and
      reduce systemic drug exposure. We compared the local (tumor) retention and
      biodistribution of 111In-labeled NR-LU-10 monoclonal antibody given i.t. in the
      injectable gel versus simple aqueous solution. 111In gel given i.t. and 111In-NR
      LU-10 given intraperitoneally (i.p.) were used as controls. The results showed
      that tumors treated with 111In-NR-LU-10 gel maintained the highest levels of
      radioactivity for up to 96 h. At 48 h after the administration of 111In-NR-LU-10
      gel i.t., 111In-NR-LU-10 solution i.t., 111In gel i.t., or 111In-NR-LU-10 i.p.,
      the level of radioactivity remaining in each gram of tumor was 98, 49, 45, and
      16% of the injected dose, respectively. It was estimated that if 100 microCi of
      90Y-NR-LU-10 were administered similarly, tumor treated with 90Y-NR-LU-10 gel
      i.t. would receive a dose of 90.0 Gy, whereas normal tissues in the same animal
      would receive a dose of approximately 2.43 Gy. In contrast, if 90Y-NR-LU-10 were
      delivered i.p., a comparable tumor would receive a dose of 16.8 Gy and
      corresponding normal tissues would receive 3.36 Gy. Consistent with these
      estimates, enhanced antitumor efficacy was observed when 90Y-NR-LU-10 gel was
      administered i.t. Tumor growth delay time was 6.9-fold (P < 0.01) longer in these
      animals (14.4 days) than in animals treated with 90Y-NR-LU-10 i.p. (2.1 days).
      Systemic toxicity was also significantly reduced in gel-treated animals as
      monitored by loss of body weight. This study demonstrated that intratumoral
      delivery of 90Y-NR-LU-10 gel markedly increased the retention of the radioisotope
      in tumors, enhanced the antitumor efficacy, and reduced systemic toxicity
      compared to systemic administration of the radiolabeled antibody. This injectable
      gel drug delivery system may allow for improvement in the therapeutic index for
      RIT.

PMID- 8735486
TI  - Correction for the use of the SOMA LENT tables. American and European LENT
      Working Committees.

PMID- 8735487
TI  - Radiotherapy for early infradiaphragmatic Hodgkin's disease: the Australasian
      experience.
AB  - PURPOSE: To review the Australasian results of Stage I and IIA Infradiaphragmatic
      Hodgkin's Disease (IHD) treated solely by irradiation. METHODS AND MATERIALS:
      Eligible patients had IHD only and were treated by irradiation with curative
      intent over the period of 1969 to 1988. Ten radiation oncology centres from
      within Australia and New Zealand were surveyed for patient, tumour and treatment
      variables. Disease free rates, survival and complications were analysed. RESULTS:
      106 patients with IHD were studied. The average potential follow up was 9.4
      years. The male to female ratio was 3.3:1. The median age was 37.5 years.
      Histological subgroups were as follows; lymphocyte predominant 43%, mixed
      cellularity 21%, lymphocyte depleted 5%, nodular sclerosing 27% and
      unclassifiable 4%. Fifty nine patients had laparotomy of which 22 (37%) were
      positive for tumour. Nine laparotomies were performed for diagnosis and the
      remainder for staging. One patient was up-staged by laparotomy and three were
      down-staged. Sixty-eight patients presented with inguinal disease alone, five
      with abdominal disease alone, 19 with two sites of involvement and 12 with
      inguinal, pelvic and abdominal disease. In two patients the site was unknown.
      There was no correlation between site of involvement, age, sex or histological
      subtype. Forty seven cases were clinically staged (CS) as follows: CS IA-23, CS
      IIA-24. The other 59 were pathologically staged (PS) as follows: PS IA-37, PS IB
      1, PS IIA-21. Treatment consisted of involved field alone (16), inverted Y (68),
      inverted Y and spleen (13), para-aortic irradiation only (3), or total nodal
      irradiation (6). Mean dose was 37 Gy. There were 30 recurrences to give an
      acturial 10-year disease-free rate of 70%. In multivariate analysis lower number
      of tumour sites, lymphocyte predominant histology and higher dose were all
      significantly correlated with higher disease free rates. Eight patients died of
      Hodgkin's disease and 19 of other causes. The 10-year overall survival rate was
      71%. Older age and higher number of disease sites were significantly correlated
      with shorter survival. Fourteen of 30 relapses may have been avoidable by the use
      of total nodal irradiation. In particular ten of 21 patients with abdominal
      disease relapsed in nodal sites which would have been covered by total nodal
      irradiation. CONCLUSIONS: The rate of control in IHD could perhaps be improved by
      avoiding involved field irradiation or by aggressive therapy with total nodal
      irradiation or combined modality chemo-irradiation in Stage II disease. Staging
      laparotomy does not appear to be indicated.

PMID- 8735488
TI  - Results of radiotherapy for squamous cell carcinoma of the vermilion border of
      the lower lip. A retrospective analysis of 108 patients.
AB  - The authors analyzed the clinical history, tumor histology and stage, and outcome
      of a group of 108 patients with squamous cell carcinoma (SCC) of the vermilion
      border of the lower lip who underwent radiation therapy in the period between
      1980 and 1992. The median follow-up was 77 months. The disease stages were T1 in
      89 (82.4%), T2 in 17 (15.7%), and T3 in 2 cases (1.9%). At presentation, regional
      lymph nodes were clinically negative in all but 3 patients. The total tumor dose
      varied from 48 Gy to 70 Gy, depending on the radiation modality (orthovoltage,
      electrons, photontherapy and iridium implants). Local control was achieved in 88
      out of 89 (98.9%) patients with T1, in 13 out of 17 (76.5%) patients with T2 and
      in both patients with T3 tumors. Local treatment failures (4.6%) were cured by
      salvage surgery. During follow-up, regional lymph node metastases at level I
      (submental and submandibular groups) occurred in 11 out of 89 (12.4%) patients
      with stage I and in I out of 15 (6.7%) patients with stage II tumors. All these
      patients underwent therapeutic neck dissection, followed by radiotherapy in 8
      cases. Two patients developed distant metastases. Thus, after salvage treatment
      of local failures and regional metastases the total group of patients with stage
      I and II SCCs of the vermilion border of the lower lip showed a definitive
      control rate of 98.1%.

PMID- 8735489
TI  - Seven fractions of twice daily high dose-rate brachytherapy for node-negative
      carcinoma of the mobile tongue results in loss of therapeutic ratio.
AB  - From June 1989 to December 1993, a Phase I/II protocol using high dose-rate (HDR)
      interstitial brachytherapy for early stage node-negative squamous cell carcinoma
      of the mobile tongue was undertaken to assess the toxicity and efficacy of this
      modality. A total of 27 patients were treated: T1-10 patients, T2-15 patients,
      and T3-two patients. Seven fractions x 6.5 Gy of HDR brachytherapy were given on
      a twice daily schedule, with a minimum interval time of 6 h, over a period of 3.5
      days. The actuarial tumor control probability after HDR brachytherapy was 53% at
      5 years. Local control rates for the T1 and T2 tumors were lower than comparable
      historical controls treated at our institution using low dose-rate (LDR) radium
      or cesium needle implants and iridium wire implants. This is despite the fact
      that the HDR schedule was calculated by the linear quadratic formula to have
      equal tumor killing effects as 60 Gy in 6 days of LDR radiation. In addition,
      there was a trend towards higher incidence of severe complications for the HDR
      patients compared to historical controls treated with LDR. We would caution
      against the use of this schedule of HDR brachytherapy until further studies are
      done.

PMID- 8735491
TI  - Wedge factors: dependence on depth and field size.
AB  - Wedge factor (WF) variation with field size and depth has been analysed for 6 and
      15 MV X-ray beams. The measured field size effect is 1.4% in the worst case,
      whereas the WF shows a linear dependence with depth giving a maximum variation of
      0.22%/cm (60 degrees wedge, 6 MV beam). An empirical correction for WF depth
      dependence on wedge thickness is proposed.

PMID- 8735490
TI  - Accuracy of pelvic radiotherapy: prospective analysis of 90 patients in a
      randomised trial of blocked versus standard radiotherapy.
AB  - The aim of this study was to assess the accuracy of pelvic radiotherapy during a
      trial of blocked radiotherapy at the Royal Marsden Hospital, UK. Prospective
      evaluation was performed on 90 patients receiving CT planned pelvic radiotherapy
      using weekly anterior-posterior and lateral portal films. Field placement errors
      (FPEs) were calculated by comparing field centres of each film with a designated
      point of interest. Data was evaluated to calculate the overall treatment
      simulator differences, the number of error free treatments, and mean treatment
      simulator position and to evaluate the role of systematic versus random errors.
      Age, weight, disease site, position of treatment, fractionation, blocked versus
      conventional techniques were assessed for their effect on treatment accuracy. The
      mean absolute error between treatment and simulator films was anterior right-left
      (ARL) 0.25 cm, anterior superior-inferior (ASI) 0.32 cm, lateral anterior
      posterior (LAP) 0.42 cm, and lateral superior-inferior (LSI) 0.28 cm. On average
      the field centre was displaced by 0.66 cm (standard deviation, S.D. = 0.34) from
      that intended. On each treatment day 29% of anterior films and 45% of lateral
      films had at least one 0.5 cm error. Overall 59% of treatments had at least one
      0.5 cm error and 9% a 1.0 cm error. The field centre was more than 0.5 cm from
      the position intended in 66% of treatments and over 1 cm for 14% of treatments.
      Analysis of variance showed that both random and systematic errors occurred in
      all directions. Though random errors were of similar magnitude in all direction
      (variance sigma 2 = 0.06-0.09 cm2); systematic errors showed a 4-fold variation
      being greatest in the LAP direction (sigma 2 = 0.19 cm2) and least the ARL
      direction (sigma 2 = 0.048 cm2). No factor consistently predicted for worse
      outcome in all directions. Hypofractionated treatments were less accurate in the
      LSI direction (P > 0.05). Systematic errors were associated in the ARL direction
      with hypofractionation (P < 0.01) and, in the LSI direction with weight (P <
      0.03) and age (P < 0.05). We conclude that significant random and systematic
      errors can occur during pelvic radiotherapy especially in the LAP direction.
      These results suggest that in the absence of a customised immobilisation device,
      to cover 95% of errors, margins of 0.6 cm for RL and SI directions and 0.9 cm for
      AP direction should be allowed between the planning and clinical target volumes.
      However, ideally, each centre should determine their own margin requirements
      according to local clinical practice.

PMID- 8735492
TI  - Time course of radiation-induced apoptosis in the adult rat spinal cord.
AB  - Radiation-induced apoptosis has been reported in thymic, lymphoid, haematopoietic
      cells and intestinal epithelium but is infrequently documented in other adult
      mammalian cell types. In this study, we examined the time course of radiation
      induced apoptosis in the adult cervical rat spinal cord following a single dose
      of 8 or 22 Gy. Apoptosis was assessed by morphological criteria under light and
      electron microscopy, and immunohistochemically in-situ using Apoptag to detect 3'
      -OH ends of DNA fragments. Little evidence of apoptosis (0.3 +/- 0.1 apoptotic
      nuclei per spinal cord section) was observed in control un-irradiated spinal
      cord. A significant increase in the number of apoptotic cells per spinal cord
      section was seen at 4 h after 8 (13.6 +/- 1.3) or 22 Gy (22.0 +/- 2.7). The
      number of apoptotic nuclei reached a peak at 8 h (44.7 +/- 3.7 after 8 Gy, 49.5
      +/- 4.3 after 22 Gy), and returned to the baseline level by 24 h (2.4 +/- 0.7
      after 8 Gy, 3.3 +/- 0.7 after 22 Gy). A dose of 22 Gy induced significantly more
      apoptoses than 8 Gy at 4, 6, 10 and 12 h (P < or = 0.033), but not at 8 h. More
      apoptotic nuclei were observed in white matter (64-92%) than gray matter (8-36%).
      All the apoptotic cells were observed in glial cells, and there was no evidence
      of radiation-induced apoptosis in the vascular endothelial cells or neurons. The
      morphological features of the apoptotic cells under electron microscopy and the
      absence of GFAP staining suggested that they were oligodendrocytes. We conclude
      that radiation induces apoptosis in the adult rat spinal cord, and that the
      development of apoptosis follows a specific time course.

PMID- 8735493
TI  - Ionizing radiation-induced phosphorylation of RPA p34 is deficient in ataxia
      telangiectasia and reduced in aged normal fibroblasts.
AB  - Replication protein A (RPA, also called human single stranded DNA binding
      protein, hSSB) is a trimeric, multifunctional protein complex involved in DNA
      replication, DNA repair and recombination. Phosphorylation of RPA p34 subunit is
      observed after exposure of cells to radiation and other DNA damaging agents,
      which implicates the protein not only in repair but also in the regulation of
      replication on damaged DNA template. Here, we show that the phosphorylation
      observed in RPA p34 after exposure to ionizing radiation, X- or gamma-rays, is
      reduced and occurs later in primary fibroblasts from patients suffering from
      ataxia telangiectasia (AT), as compared to normal fibroblasts. We also show that
      in primary normal human fibroblasts, radiation-induced phosphorylation of RPA p34
      is 'age'-dependent and decreases significantly as cultures senesce. Radiation
      induced phosphorylation of RPA p34 is nearly absent in non-cycling cells, while
      the expression of p21cipl/wafl/sdil remains inducible. The results demonstrate a
      growth-state and culture-age dependency in radiation-induced RPA p34
      phosphorylation, and suggest the operation of a signal transduction pathway that
      is inactivated in senescing or quiescent fibroblasts and defective in AT cells.

PMID- 8735495
TI  - Interactions of BMS-181174 and radiation: studies with EMT6 cells in vitro and in
      solid tumors.
AB  - N-7[2-(4-nitrophenyldithio)-ethyl] mitomycin C, (BMS-181174; previously
      designated as BMY25067) is a mitomycin C analog now in initial clinical trials.
      The experiments described in this report were performed to assess whether BMS
      181174, like mitomycin C and porfiromycin, was selectively toxic to the hypoxic
      cells in solid tumors and might therefore prove valuable in combination with
      radiotherapy. In contrast to mitomycin C and porfiromycin, BMS-181174 was more
      toxic to aerobic EMT6 cells in vitro than to cells made acutely hypoxic. In
      vitro, BMS-181174 and radiation produced cytotoxicity compatible with either
      additive or slightly supra-additive cytotoxicity. In vivo, BMS-181174 was
      effective in killing cells in solid EMT6 tumors. The effects of regimens
      combining BMS-181174 and radiation in vivo were complex. Combinations of low
      doses of BMS-181174 plus a large dose of radiation were very effective in killing
      cells in solid tumors. However, the survival curve plateaued at high doses of BMS
      181174, providing evidence for a subpopulation of tumor cells which were
      resistant to both BMS-181174 and radiation; this was hypothesized to be a hypoxic
      cell population.

PMID- 8735494
TI  - Radiosensitisation in normal tissues with oxygen, carbogen or nicotinamide:
      therapeutic gain comparisons for fractionated x-ray schedules.
AB  - METHODS: Radiosensitisation with oxygen, carbogen or nicotinamide alone and
      oxygen or carbogen combined with nicotinamide was compared in early and late
      responding normal tissues in rodents. X-ray treatments were delivered as single
      doses or fractionated schedules of 2 fractions in 1 day, 2, 12 and 36 fractions
      in an overall time of 12 days and 10 fractions in 5 or 12 days. Acute skin
      reactions, survival of intestinal crypts, breathing rate, reduction in the packed
      red-cell volume and clearance of 51Cr-EDTA were used as assays of epidermal, gut,
      lung and renal damage. RESULTS: Relative to air-breathing mice, carbogen or
      oxygen produced a small, and not always significant, increase in sensitivity
      (enhancement ratios < or = 1.15) in gut, lung and kidneys; however, in skin a
      dose enhancement of 1.2-1.3 was observed. The effect of nicotinamide in air,
      carbogen or oxygen was studied only in lung and gut. The drug produced variable
      but generally significant increases in radiosensitisation ( < or = 1.26) in all
      three gases. Relative to treatments in air, enhancement ratios for nicotinamide
      alone were usually slightly higher than those observed when either carbogen or
      oxygen were administered without the drug. With all three modifiers (i.e. oxygen,
      carbogen, nicotinamide alone or for the drug-gas combinations) there was no
      significant change in the enhancement ratios observed as the number of radiation
      dose fractions was varied. CONCLUSIONS: Comparisons with fractionated X-ray
      studies done previously in rodent tumours indicate that a therapeutic benefit,
      relative to lung, gut and renal damage, would be observed with oxygen or carbogen
      alone but not with nicotinamide alone. The greatest gain would be achieved with
      the combination of carbogen and nicotinamide, with which a benefit was observed
      even relative to epidermal damage. These results indicate that some decrease in
      normal tissue tolerance could be observed when using these modifiers in clinical
      radiotherapy and, although small, the appropriate dose reductions should be
      considered; caution should be exercised especially when carbogen and nicotinamide
      are used in conjunction with the more radical accelerated schedules.

PMID- 8735496
TI  - Differential effects of dose rate and superfractionation on survival and cell
      cycle of V79 cells from spheroid and monolayer culture.
AB  - Recent developments concerning brachytherapy suggest conditions for an
      equivalence between the common continuous low dose rate (CLDR) exposure and
      pulsed irradiation regimens (PDR), provided that total dose is administered in
      the same overall time. The respective theoretical considerations have been based
      solely on the phenomenon of sublethal damage recovery. The present study,
      therefore, aimed to assess a possible influence of growth state/cell cycle
      progression when CLDR and different super fractionation protocols are compared.
      The respective experiments were performed with V79 cells that can be grown as a
      rapidly proliferating monolayer culture or as small spheroids (without hypoxia)
      where most of the cells are out of cycle. Differential changes in cell cycle
      distribution occurring during the compared exposure schemes and their impact on
      cell survival were expected to be expressed most clearly with this model system
      because of the short G1 phase. Cell irradiations were performed with
      brachytherapy sources either continuously (137Cs) or with high dose rate pulses
      (192Ir) at different (1 h and 4 h) pulse repetitions whereby the overall dose
      rate was kept constant to approximately 1 Gy/h. Cell survival curves were
      generated by sampling cells at different exposure times or number of pulses,
      respectively. For spheroid cells an unequivocal decrease of effectivity was
      demonstrated with decreasing dose per pulse, and the dose effect relation
      obtained with hourly pulses of 1 Gy was indistinguishable from the CLDR response.
      For monolayer cells, on the contrary, the scheme of hourly pulses was
      significantly more effective than the CLDR irradiation. As measured by flow
      cytometry, this different behaviour could be attributed to the accumulation of
      cycling cells in the radiosensitive G2/M phase (G2 block) during protracted
      exposure which was drastically more pronounced for the pulsed scheme compared to
      the CLDR condition. The observed principle phenomenon of a block to cell cycle
      progression from high dose rate pulses (at low overall dose rate) may be less
      expressed in (human) cells having a long G1 period, but if applicable to a
      clinical situation, an increase of acute effectiveness of a superfractionated
      brachytherapy protocol has to be considered.

PMID- 8735498
TI  - Implantable cardioverter-defibrillators.

PMID- 8735497
TI  - Cross resistance and collateral sensitivity between cytotoxic drugs and radiation
      in two human bladder cell lines.
AB  - The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) test was employed
      as a means of studying the cross resistance and collateral sensitivities of two
      bladder cell lines able to grow in the presence of several antineoplastic drugs
      and/or despite the effects of radiotherapy. This cross resistance and collateral
      sensitivities were investigated in the context of two antineoplastic drugs (i.e.
      doxorubicin (an anthracycline) and vinorelbine (a Vinca alkaloid) and
      radiotherapy. The results show that cell lines able to grow in the presence of
      anticancer drugs develop a significant degree of resistance to antineoplastic
      compounds and may also develop resistance to radiotherapy. On the other hand,
      most cell lines treated first with radiotherapy develop a significant degree of
      resistance towards ionizing radiation and may also display increased sensitivity
      towards anticancer drugs. If these results obtained in vitro are clinically
      relevant, they may have important applications in the treatment of patients.
      Nevertheless, it will be necessary to validate the results on extensive series of
      chemo- and/or radioresistant cell lines exhibiting different mechanisms of
      resistance.

PMID- 8735499
TI  - Update on Creutzfeldt-Jakob disease.

PMID- 8735500
TI  - Seasonality of birth in sudden infant death syndrome.
AB  - The objective was to clarify the optimal birth month for avoidance of SIDS and
      the seasonal characteristic of each birth-month cohort. The statistical method
      was cosinor analysis, and this established seasonality of SIDS death and births,
      the extent of this seasonality (amplitude) and the position of the peak
      (acrophase). There is a lowering of risk, by one third, amongst babies born in
      February-May compared to those born in August-November. The seasonal variation of
      death was twice as great for birth in September as compared with those in April.
      Those born in May-June lived on average six weeks longer than those born in
      November-April. Advice on subsequent pregnancy delivery date should be given to
      families who have already experienced SIDS. For those born in autumn there may be
      two components-the first a genetic or intrauterine component independent of month
      of birth, and the second an independent effect of interaction with winter
      environment.

PMID- 8735501
TI  - A medical audit and patient survey of hysterectomies performed for menstrual
      disorders.
AB  - The aim of the study was to carry out an audit of 283 hysterectomies performed
      for menstrual disorders over a one year period, and to determine the satisfaction
      of the women concerned towards their treatment. The medical records of these
      patients were examined, and they were each sent a questionnaire, 69% of which
      were completed and returned. The most common presenting symptoms were menorrhagia
      and dysmenorrhoea. In 53% of cases no clinical abnormality was postulated and in
      31% of cases no pathological abnormality was found. The preoperative clinical and
      pathological diagnoses were in agreement for 59% of patients. Over 90% of women
      were satisfied with the management of their case by their GP and the gynaecology
      outpatient clinic. The use of patient-controlled analgesia systems was associated
      with better post-operative pain relief than intramuscular injections. Thirteen
      percent of patients required blood transfusion; 21% suffered some form of
      postoperative complication, most of which were minor. Ninety-four percent of the
      women were pleased that they had undergone hysterectomy, and 76% wished that they
      had had the operation sooner. It was concluded that hysterectomy is perceived
      positively by patients and should not necessarily be considered as a last resort
      treatment for menstrual disorders.

PMID- 8735502
TI  - Defibrillation--a burning issue in coronary care units!
AB  - Skin burns are accepted to be a complication of defibrillation, however there is
      no published data on their frequency, cause and treatment. A postal questionnaire
      survey was designed to assess the relative frequency of defibrillation burns in
      coronary care units and identify the possible factors contributing to their
      occurrence. Treatments prescribed in coronary care units were also noted. The
      questionnaire was sent to the Senior Sister/Charge Nurse in all 263 coronary care
      units in the United Kingdom. 232 Replies were received (88.2%). Defibrillation
      burns were seen in 98.7% of CCU's. Ten contributory factors were proposed. The
      commonest implicated cause was recurrent defibrillation. The most frequently
      prescribed topical treatment was 1% silver sulphadiazine cream (Flamazine).
      Defibrillation burns are relatively common in coronary care units. Many result
      from recurrent defibrillation and may be unavoidable in the patient undergoing
      prolonged resuscitation. However there are other identifiable factors which, if
      avoided, may lead to a reduction in the number of burns seen.

PMID- 8735503
TI  - Management of suspected acute venous thromboembolism in a general and maternity
      hospital.
AB  - A retrospective study of the management of patients with suspected acute deep
      venous thrombosis (DVT) and pulmonary thromboembolism (PTE) in a general and
      maternity hospital was conducted over a two month period in 1992. Ninety six
      patients with suspected DVT/PTE were identified, of whom only two were pregnant.
      Forty four patients had suspected DVT and confirmatory investigations were
      performed in 84%. The most common risk factor for DVT was intra-venous drug (IVD)
      use. Unfractionated heparin was prescribed to all patients except one with acute
      DVT at an average daily dose of 25,000 iu. In patients receiving heparin, 68% had
      measurements of the activated partial thromboplastin time (APTT) ratio and on 38%
      of occasions the result was subtherapeutic. Complications of heparin therapy were
      infrequent. Fifty two patients had suspected PTE and 50 underwent
      ventilation/perfusion (V/Q) scanning. No patient underwent pulmonary angiography.
      The management of patients with normal, low and high probability V/Q scans was in
      keeping with the guidelines, but only 8% [corrected] of patients with an
      intermediate V/Q scan result had further investigations and 33% received heparin.
      This study revealed suboptimal anticoagulation of patients with acute DVT and
      scope for improvement in the management of patients with an intermediate V/Q scan
      result.

PMID- 8735504
TI  - Rectus sheath haematoma presenting with Cullen's sign and Grey-Turner's sign.

PMID- 8735505
TI  - Dry bones: a paleopathological study of skeletal remains from a medieval
      graveyard in Dundee.
AB  - We report a study on human skeletal remains excavated from a medieval city centre
      graveyard. The remains of approximately 75 individuals were examined and
      radiographs were made of selected specimens. Many bones were normal and
      apparently from strong, young adults. The most frequent abnormality was
      osteoarthritis but we also noted osteoporosis, periostitis and an example of
      probable Paget's disease. From measurements of long bones and using appropriate
      formulae, we estimated stature. The average height for males was calculated to be
      172cm (5' 7") and for females 157 cm (5' 2").

PMID- 8735506
TI  - Muscle growth and muscle function: a molecular biological perspective.
AB  - Molecular biological methods are pervading all biomedical fields and it is likely
      that they will soon introduce new techniques to veterinary diagnostics and have a
      major impact on food and fibre production in animal agriculture. The ability to
      manipulate muscle growth and phenotype will present new ethical problems,
      particularly if the techniques are used to manipulate muscle development in
      greyhounds and racehorses where the financial rewards could be very substantial.
      Muscle has been a useful tissue for the study of the molecular control of tissue
      development because terminal differentiation results in the production of large
      quantities of highly specialised proteins. Now that the functional anatomy of
      structural genes in muscle is being elucidated, a coherent picture is beginning
      to emerge of the way in which post-natal muscle growth and phenotype are
      regulated at the gene level. The hormones and growth factors involved in
      regulating the quantitative and qualitative changes in gene expression are now
      better understood, together with the ability of the tissue to adapt to physical
      signals and hence new activity patterns. The myosin heavy chain isoform genes
      which encode the myosin cross-bridges (the force generators for muscular
      contraction) exist as a large multigene family. The contractility and other
      characteristics of muscle depend to a large extent on the differential expression
      of members of this and other gene families. Muscle fibres adapt for increased
      power output by expressing a subset of "fast' genes and for increased economy of
      action by expressing a slow subset of genes and producing more mitochondria. With
      the increasing understanding of gene expression in muscle, there are prospects
      for manipulating the mass, contractility and other characteristics of muscle and
      also to change its phenotype and understand certain disease states.

PMID- 8735507
TI  - Adrenocortical function in the domestic cat during treatment with levonorgestrel.
AB  - Levonorgestrel was administered via a subcutaneous, slow-release silastic implant
      to 10 queens. Five other queens served as controls. Their adrenocortical function
      was assessed by the adrenocorticotrophic hormone (ACTH) stimulation test before
      and after one, two, six and 12 months of treatment. In addition, the gross
      anatomy and histology of the adrenal gland were examined post mortem in six of
      the treated cats. In both the control and treated queens the plasma cortisol
      concentrations (pre and post ACTH) were significantly different (P < 0.05) at
      different times. However, there were no significant differences between the
      plasma cortisol concentrations (pre and post ACTH) of the treated and control
      queens. No gross or microscopical abnormalities were visible in the adrenal
      glands of the treated queens.

PMID- 8735508
TI  - Adverse haemodynamic effects of the rapid intravenous injection of hypotonic
      solutions in sheep.
AB  - The rapid intravenous administration of 10 ml of sterile water or hypotonic
      saline to five conscious sheep induced substantial adverse haemodynamic effects
      lasting 10 to 20 seconds. They included reductions in cardiac output (to 44 per
      cent of the baseline value measured in the 30 seconds before the injection),
      arterial blood pressure (67 per cent of baseline), left ventricular systolic
      pressure (60 per cent of baseline), myocardial contractility (60 per cent of
      baseline), and left coronary arterial blood flow (39 per cent of baseline), and
      increases in heart rate to 137 per cent of the baseline. The intensities of these
      effects were related directly to the rates of injection and inversely to the
      osmolalities of the solutions injected. Intravascular haemolysis was associated
      with the effects. These data are of potential importance to anyone administering
      drugs intravenously to sheep.

PMID- 8735509
TI  - Pharmacokinetics of propofol infusions, either alone or with ketamine, in sheep
      premedicated with acepromazine and papaveretum.
AB  - The pharmacokinetics of propofol were investigated in two groups of five Scottish
      blackface sheep undergoing surgery for the implantation of subcutaneous tissue
      pouches. After premedication with acepromazine and papaveretum, anaesthesia was
      induced with either propofol at 4 mg kg-1 intravenously (group 1) or with a
      mixture of propofol at 3 mg kg-1 and ketamine at 1 mg kg-1 intravenously (group
      2). Anaesthesia was maintained with a variable infusion rate of either propofol
      alone (group 1) or propofol and ketamine (group 2). Both regimens produced
      satisfactory conditions for superficial surgery of the body surface. The mean
      (SD) duration of anaesthesia was 64.8 (3.1) minutes for group 1 and 60 (0)
      minutes for group 2; the mean total dose of propofol given to the sheep in group
      1 was 801 (84) mg, and the sheep in group 2 received 470 (46) mg of propofol and
      267 (30) mg of ketamine. The mean elimination half-life of propofol was 56.6
      (13.1) minutes in group 1 and 50.3 (21.4) minutes in group 2; the mean volume of
      distribution at steady state was 1.037 (0.480) litre kg-1 in group 1 and 1.515
      (0.939) litre kg-1 in group 2; the mean body clearance was 85.4 (28.0) ml kg-1
      min-1 in group 1 and 128.0 (35.0) ml kg-1 min-1 in group 2; the mean residence
      time corrected for a bolus injection was 12.1 (4.2) minutes in group 1 and 11.9
      (6.6) minutes in group 2; for the infusion, the mean residence time was 72.1
      (4.2) minutes in group 1 and 69.9 (7.9) minutes in group 2. There were wide
      variations in the blood propofol concentrations reached in individual sheep by
      using this standard dosing regimen. All the sheep recovered quickly from
      anaesthesia; the mean times to extubation, sternal recumbency and standing for
      the animals in group 1 were 2.8 (0.4), 6.3 (1.2) and 10.9 (1.6) minutes from the
      end of the infusion, and the times for group 2 were 5.3 (0.9), 11.2 (1.7) and
      15.1 (2.2) minutes.

PMID- 8735510
TI  - An improved DNA test for bovine leucocyte adhesion deficiency.
AB  - A modified DNA test, based on the polymerase chain reaction, was developed for
      the monogenic recessive disease bovine leucocyte adhesion deficiency (BLAD). The
      test was improved by the selection of new primers which facilitated the
      interpretation of the results. An easily scorable banding pattern makes the test
      useful in cattle breeding schemes and for clinical diagnosis. A total of 2381
      samples was analysed over a period of three years. The carrier rate among young
      bulls at artificial insemination (AI) stations decreased from 11.6 per cent in
      1993 to 9.9 per cent in the first five months of 1995. Continuous screening of
      young bulls before entering AI is still recommended unless both parents are
      proven to be genetically free of BLAD. The carrier rate among clinically suspect
      animals was not increased, and carriers are therefore not expected to be
      immunodeficient. Despite all efforts to eradicate the disease, calves with BLAD
      were still observed in 1995.

PMID- 8735511
TI  - Characterisation of colony-stimulating activity in the avian T cell-derived
      factor, Salmonella enteritidis-immune lymphokine.
AB  - This investigation was designed to characterise the specific cytokine activity
      from the conditioned medium of concanavalin A-stimulated avian T cells derived
      from Salmonella enteritidis-immune chickens, S enteritidis-immune lymphokine
      (ILK). Studies were designed to determine first, whether colony-stimulating
      activity was present in ILK, second, the type(s) of colonies from the bone marrow
      that were supported in vitro by the potential colony-stimulating factors in ILK
      and, third, whether colony-stimulating activity was present in serum from chicks
      treated with ILK and challenged with S enteritidis, and to use physicochemical
      treatment as a means of identifying the potential colony-stimulating factor(s) in
      ILK. Both ILK alone and serum from chicks treated with ILK and challenged with S
      enteritidis caused significant increases in the number of colony-forming units
      (CFU) from the bone marrow in vitro. After 10 days of incubation, ILK alone
      supported the in vitro growth of granulocytic bone marrow colonies. The colony
      stimulating activity from serum derived from chicks treated with ILK and
      challenged with S enteritidis peaked two hours after the challenge. When ILK was
      either heated at 100 degrees C or treated with trypsin or acid and then injected
      into chicks, all the chicks responded with significant increases in circulating
      polymorphonuclear leucocytes (PMNs). However, when assayed for in vitro colony
      stimulating activity, only trypsinisation destroyed the activity in ILK. The
      results indicate that a colony-stimulating factor which preferentially supported
      the growth of granulocytic bone marrow colonies was present in ILK and that the
      factor was stable to heat and acid but sensitive to trypsin.

PMID- 8735512
TI  - Infection of pigs by aerosols of Aujeszky's disease virus and their shedding of
      the virus.
AB  - On three consecutive days, six pigs were exposed for 15 minutes to aerosols of
      Aujeszky's disease virus. The total estimated dose was 4.5 log 10 TCID50. Within
      each isolation room, a sentinel pig was placed on a deck two feet away from the
      infected pig. The breath of the pigs that had inhaled the aerosols was collected
      on days 3, 7 and 13. The respiratory and other clinical signs of the infected
      pigs resembled those in field cases of Aujeszky's disease. All the pigs infected
      with Aujeszky's disease virus seroconverted within seven to 10 days after
      infection. Among the sentinel pigs, clinical signs were minimal and only three
      seroconverted.

PMID- 8735513
TI  - Effect of age on the pharmacokinetics of antipyrine in calves.
AB  - Single doses of 15 mg kg-1 antipyrine were given intravenously to 10 female
      calves of the black and white breed at one, two, four, six, eight and 12 weeks of
      age, and the concentrations of antipyrine, 4-hydroxyantipyrine (4-OHA), 3
      hydroxymethyl-antipyrine (HMA) and norantipyrine (NORA) were measured in plasma
      and urine by high performance liquid chromatography. The first three months of
      life were characterised by a steady decrease in the apparent volume of
      distribution (aVd) and half-life (t0.5) of antipyrine. The systemic clearance
      (CIs) of antipyrine per unit bodyweight increased significantly between one and
      12 weeks of age. Age did not influence the excretion of HMA and NORA in urine,
      but the excretion of 4-OHA by 12-week-old calves was significantly greater than
      by one-week-old calves. There was an age-related change in the partial clearances
      of the antipyrine metabolites when expressed per unit bodyweight.

PMID- 8735514
TI  - Minor constituents of sabulous material in equine urine.
AB  - The secondary constituents accompanying calcite and vaterite (crystalline forms
      of calcium carbonate) in the sabulous deposits from 140 vesical samples and one
      renal sample of equine urine were studied by infrared spectroscopy (IR), scanning
      electron microscopy (SEM) and energy dispersive X-ray analysis (EDX). Apatitic
      calcium phosphate, present in 12 per cent of the samples, generally appeared in
      the form of spherulites with smooth and rough surfaces. Calcium sulphate, clearly
      detected by IR in 12.7 per cent of the samples, did not have a characteristic
      structure under SEM, although EDX detected sulphur in the samples. Amorphous
      silica was observed in one case and had a nodular appearance. Organic fibres were
      not as common as might have been expected in equine urinary deposits.

PMID- 8735515
TI  - Assessment of orocaecal transit time in cats by the breath hydrogen method: the
      effects of sedation and a comparison of definitions.
AB  - Oro-caecal transit times (OCTTs) were assessed in 10 healthy adult cats by the
      lactulose breath hydrogen method with either no sedation (group A), or after the
      intramuscular administration of three sedative regimens: a combination of
      acetylpromazine at 0.1 mg kg-1 with buprenorphine at 10 micrograms kg-1 (group
      B), ketamine at 5 mg kg-1 with midazolam at 0.1 mg kg-1 (group C), or
      medetomidine at 50 micrograms kg-1 (group D). For each test, the OCTT was defined
      by four methods: a visual assessment, the first maintained 4 ppm increase in
      hydrogen production, and the first maintained 0.5 ml hr-1 increase in hydrogen
      production assessed by two cumulative sum methods. Depending on the definition,
      the median OCTTs of the cats were between 113 and 131.5 minutes in group A, 86.5
      and 97.5 minutes in group B, 218 and 235.5 minutes in group C and 86.5 and 97.5
      minutes in group D. By two of the definitions, the median OCTTs in group C were
      significantly longer than in group A (P < or = 0.037) and approached significance
      by the other two definitions. The use of sedatives significantly increased the
      inter-individual variability of the OCTTs, particularly in groups C and D. There
      were significant differences between the median OCTTs defined by the four
      different methods, but all the methods were very highly and significantly
      correlated (rs < or = 0.9503, P < 0.0001).

PMID- 8735516
TI  - Simple method for the perfusion-fixation of adult bovine brain.
AB  - It is widely accepted that the vascular perfusion of a tissue leads to its
      optimal fixation for ultrastructural examination, but the technique has been
      applied with little success in large animals such as cattle. This paper describes
      a simple and highly reproducible method for the perfusion-fixation of adult
      bovine brain. The carotid arteries are cannulated and the perfusate is introduced
      by means of a peristaltic pump. The inclusion of toluidine blue in the fixative
      makes it possible to assess the success of the technique, and prevents the costly
      and time-consuming processing of material which is suboptimally fixed. The method
      is potentially valuable for the examination of a wide range of neurological
      conditions in large domestic animals at an ultrastructural level in optimally
      fixed material.

PMID- 8735517
TI  - Relationship between receptors for epidermal growth factor and steroid hormones
      in normal, dysplastic and neoplastic canine mammary tissues.
AB  - The concentrations of receptors for epidermal growth factor (EGF-R), oestrogen
      (ER) and progesterone (PR) were measured in 108 samples from canine mammary
      tumours and 132 samples of normal mammary tissue removed surgically from 84
      bitches. The history and clinical signs were also recorded. Binding sites of high
      affinity were detected in 70 per cent of both types of tissue and no significant
      variations in EGF-R concentrations or positivity were observed with the
      histology, location, size or number of mammary tumours or the age of the animal.
      A significant direct correlation (P = 0.002) was observed between the
      concentrations of ER and EGF-R only in malignant tumours. The concentrations of
      EGF-R were significantly correlated (P = 0.04) in normal mammary tissues adjacent
      to and distant from the lesions, but not between normal tissue and tumour tissue.
      No significant differences were observed in the expression of EGF-R in normal and
      neoplastic tissues from the same bitches. The direct correlation between the
      concentrations of EGF-R and ER in malignant tumours could be related to an
      oestrogen-dependent expression of EGF-R or to a similar pattern of regulation of
      the receptors.

PMID- 8735518
TI  - Changes in the release of amino acid neurotransmitters in the brains of calves
      and sheep after head-only electrical stunning and throat cutting.
AB  - In calves aged two to five months, throat cutting resulted in an increase in the
      concentration of the amino acid neurotransmitters glutamate and aspartate in the
      brain. Electrical head-only stunning by itself also increased the concentrations
      of these two neurotransmitters. The levels induced by stunning resulted in a
      seizure state characterised by epileptiform-like activity in the
      electroencephalograph. Combing head-only stunning with throat cutting within 10
      seconds of the stun had a synergistic effect upon glutamate and aspartate,
      increasing their concentration by a greater amount and more quickly than either
      procedure on its own. An irreversible loss of brain function also occurred more
      quickly than after throat cutting alone. The administration of glutamate and
      aspartate receptor antagonists before the throat cutting lengthened the time to
      the loss of brain function in a dose dependent manner. Similar changes were
      observed in sheep but they occurred much more quickly than in cattle.

PMID- 8735519
TI  - Simultaneous infusions of propofol and ketamine in ponies premedicated with
      detomidine: a pharmacokinetic study.
AB  - The pharmacokinetics of propofol and ketamine administered together by infusion
      were investigated in four ponies. Blood propofol and plasma ketamine and
      norketamine concentrations were measured by high performance liquid
      chromatography. After premedication with detomidine (20 micrograms kg-1)
      anaesthesia was induced with ketamine (2.2 mg kg-1 intravenously). The trachea
      was intubated and the ponies were allowed to breathe 100 per cent oxygen. A bolus
      dose of propofol (0.5 mg kg-1) was then administered intravenously and propofol
      and ketamine were infused for 60 and 45 minutes, respectively. The average mean
      infusion rate of propofol was 0.136 mg kg-1 min-1, and the ketamine infusion rate
      was maintained at 50 micrograms kg-1 min-1. The mean (SD) elimination half-lives
      of propofol and ketamine were 69.0 (8.0) and 89.8 (26.7) minutes, the mean
      volumes of distribution at steady state were 0.894 (0.161) litre kg-1 and 1.432
      (0.324) litre kg-1; the mean body clearances were 33.1 (4.5) and 23.9 (3.8) ml kg
      1 min-1 and the mean residence times for the infusion were 87.1 (4.1) and 110.7
      (8.2) minutes, respectively. Norketamine, the main metabolite of ketamine, was
      detected throughout the sampling period. The mean residence time for norketamine
      was 144 (16) minutes. All the ponies recovered quickly from the anaesthesia; the
      mean times to sternal recumbency and standing were 11.1 (5.3) and 30.0 (20.8)
      minutes, respectively, from the end of the infusion.

PMID- 8735520
TI  - Cardiopulmonary effects of medetomidine in sheep and in ponies.
AB  - Medetomidine was administered intravenously to six sheep at 5, 10 and 20
      micrograms kg-1 and to one horse and four ponies at 5 and 10 micrograms kg-1. In
      both species medetomidine resulted in significant decreases in heart rate and
      cardiac output and, initially, in an increase in arterial blood pressure. In the
      ponies this increase in blood pressure was followed by a significant and
      prolonged decrease, but in the sheep the secondary decrease in blood pressure was
      not statistically significant. In the sheep, the three doses of medetomidine
      resulted in profound and significant decreases in arterial oxygen tensions, which
      were significantly dose related, but in the ponies the arterial blood oxygen
      tensions were not significantly decreased. In both species medetomidine caused a
      small but significant increase in arterial blood carbon dioxide tensions.

PMID- 8735521
TI  - Oxygen affinity and Bohr effect responses to 2,3-diphosphoglycerate in equine and
      human blood.
AB  - The dependence of blood oxygen affinity and the Bohr effect on the concentration
      of 2,3-diphosphoglycerate (DPG) in erythrocytes was investigated in 24 trotter
      horses and 24 healthy men. The oxygen tension at half saturation and standard
      conditions (P50st at pH 7.4, PCO2(40) mmHg and 37 degrees C) and the carbon
      dioxide or fixed-acid-induced Bohr effect (dlogP50/dpH) were determined. Samples
      of fresh blood and blood depleted of or enriched with DPG were studied. In the
      absence of measurable DPG, the equine and human blood had similar mean (SD)
      values of P50st (16.6 [0.6] and 16.2 [0.7] mmHg, respectively). In both species
      these values increased with increasing DPG, but the response of equine blood was
      significantly lower, at least up to physiological values (P50st = 24.6 [0.6] and
      26.2 [0.7]) mmHg; DPG = 14([1.8] and 12.8 [1.2] mumol gHb-1, respectively, in
      fresh blood). For concentrations above 20 to 25 mumol gHb-1 of DPG the difference
      between the values of P50st in the two species tended to decrease because the
      response in human blood reached a plateau. The interactions between the Bohr
      effect and the concentration of DPG showed that in the horses, as in the men, the
      level of DPG played an important role in governing the relative magnitude of
      carbon dioxide and fixed acid factors. The difference between them, which is
      associated with the oxylabile carbamino binding, was greatest in DPG-depleted
      blood, but whereas in the men the difference was suppressed by an above normal
      DPG concentration, in the horses it was still measurable.

PMID- 8735522
TI  - Effect of dietary protein on the regulation of populations of Nematodirus battus
      by lambs.
AB  - Two groups of seven and two groups of six lambs were offered either a complete
      basal ruminant diet (13.2 per cent crude protein [CP]) (groups 2 and 4) or the
      same diet supplemented with fish meal (18.3 per cent CP) (groups 1 and 3). Groups
      1 and 2 were infected daily for seven weeks with Nematodirus battus larvae (L3)
      and groups 3 and 4 served as uninfected challenge controls. All the groups were
      treated with anthelmintic in the eighth week, challenged with a single dose of
      30,000 N battus L3 one week later and killed nine days after the challenge.
      Although protein supplementation tended to enhance the regulation of the
      population of N battus in the lambs which had been infected continuously, the
      effect was not statistically significant. The worm burdens in both the groups of
      previously infected lambs were significantly reduced both in number and size (P <
      0.001) and they had a lower proportion of male worms than the uninfected
      challenge controls. The lambs could be segregated into high or low responders on
      the basis of their worm burdens, and there was a significant reduction in worm
      burdens (P < 0.001) and size (P < 0.01) in parallel with the lambs'
      responsiveness. The identification of high and low responders shows that when the
      dietary protein supply is adequate the predominant effect of the host on the
      pathogenicity of its parasites is the host's genetically-determined
      susceptibility.

PMID- 8735523
TI  - Detection of Fasciola hepatica antigen in cattle faeces by a monoclonal antibody
      based sandwich immunoassay.
AB  - A monoclonal antibody-based sandwich immunoassay (mAb sandwich ELISA) was
      developed for the detection of Fasciola hepatica antigen in the faeces of cattle.
      The assay was applied to samples from 100 cattle infected with F hepatica, 56
      animals with parasitologically proven infections of other parasites and 100
      uninfected animals. F hepatica antigen was detected in all the faecal samples
      from animals with fasciolosis, but none of the samples from the uninfected
      animals or from those with other parasitic infections had significant levels of F
      hepatica antigens. The results indicate that the mAb sandwich ELISA is a rapid,
      simple and useful method for the diagnosis of active F hepatica infection in
      cattle.

PMID- 8735524
TI  - Urinary excretion by dogs of intravenously administered simple sugars.
AB  - Seven simple sugars, commonly used in intestinal function tests, were
      simultaneously administered intravenously to dogs and their urinary excretion was
      measured to assess their potential for metabolic degradation. Lactose, lactulose
      and 3-O-methyl-D-glucose were excreted unchanged, but small proportions of
      palatinose and sucrose were not, and were assumed to have been metabolised. More
      than half of the administered D-xylose and a quarter of L-rhamnose was not
      excreted and was assumed to have been metabolised. These findings may be
      significant for the interpretation of differential sugar absorption tests and the
      D-xylose tolerance test.

PMID- 8735525
TI  - Physical characteristics and biological effects of laser-induced stress waves.
AB  - Laser-induced stress waves can be generated by one of the following mechanisms:
      optical breakdown, ablation, or rapid heating of an absorbing medium. These three
      modes of laser interaction with matter allow the investigation of cellular and
      tissue responses to stress waves with different characteristics and under
      different conditions. The effects of stress waves on cells and tissues can be
      quite disparate. Stress waves can fracture tissue, kill cells, decrease cell
      viability and increase the permeability of the plasma membrane. They can induce
      deleterious effects during medical procedures of high power, short pulse lasers
      or, alternatively, may facilitate new therapeutic modalities, such as drug
      delivery and gene therapy. This review covers the generation of laser-induced
      stress waves and their effects on cell cultures and tissue.

PMID- 8735526
TI  - Comparison of trans- and intra-abdominal duplex examinations of the splanchnic
      circulation.
AB  - To evaluate the influence of the technical problems experienced when scanning
      transabdominally, a comparison was made between transabdominal and intra
      abdominal Doppler parameters of the aorta and the splanchnic arteries.
      Peroperative color duplex sonography of the abdominal aorta and the splanchnic
      arteries was performed on 25 patients who were undergoing abdominal vascular
      reconstructive surgery under stabilized standardised anaesthesia. Doppler samples
      and diameter measurements were taken of the aorta, celiac, common hepatic,
      splenic, superior and inferior mesenteric arteries, both trans- and intra
      abdominally. Significantly higher velocities were recorded in the celiac artery
      during intra-abdominal examinations. There was a trend toward higher recorded
      velocities in the other vessels. There was also a significant difference in the
      diameter measurements of most of the vessels. The trans- and intra-abdominal
      results were not always equivalent. The differences were not due to technical
      aspects. Transabdominal duplex sonography is difficult and may not be completely
      accurate in detecting quantitative flow parameters in the splanchnic arteries.

PMID- 8735527
TI  - Transcranial Doppler sonography at the early stage of acute central nervous
      system infections in adults.
AB  - Transcranial Doppler sonography (TCD) of the middle, anterior and posterior
      cerebral arteries and of the basilar artery was used to evaluate the mean blood
      velocity (V mean) and the pulsatility index [PI = (V systolic-V diastolic)/V
      mean] as a vascular resistance index in 63 patients (male 40, female 23, mean age
      43 +/- 19 y) with bacterial meningitis (n = 33, including 2 patients with fungal
      meningitis) and viral meningitis (n = 30) within 12 h after admission of the
      patients. The findings were similar for all intracranial arteries. Compared with
      reference values of 69 healthy volunteers [V mean of middle cerebral artery [MCA]
      57 +/- 13 cm/s, MCA-PI 0.83 +/- 0.15], MCA-V mean was increased in patients with
      Glasgow coma scale (GCS) scores of 14 and 15 (71 +/- 18 cm/s; t-test: p < 0.001),
      not significantly different in the patients with GCS scores of 10-13 (55 +/- 21
      cm/s) and decreased in those with GCS scores of 3-9 (42 +/- 21 cm/s, p < 0.01).
      The MCA-PI increased from 0.93 +/- 0.22 in the patients with GCS scores of 14-15
      to 2.81 +/- 2.06 in those with GCS scores of 3-9 (p < 0.001 vs. controls). By
      regression analysis, MCA-V mean decreased and MCA-PI increased with decreasing
      GCS scores (p < 0.001). Only in patients with bacterial meningitis was the
      Glasgow outcome scale (GOS) score lower the more the MCA-PI was increased
      (regression analysis p < 0.001). We conclude that in patients with bacterial and
      viral meningitis, and in a good clinical state, the cerebral blood flow seems
      increased by hyperemia; with clinical deterioration the cerebral haemodynamics
      worsen. However, the early assessment of the cerebral blood flow by TCD seems
      useful for predicting outcome in bacterial meningitis only.

PMID- 8735528
TI  - Application of focused ultrasound for the stimulation of neural structures.
AB  - The feasibility of the use of focused ultrasound for stimulation of the
      superficial and deep-seated receptor structures of humans and animals are
      presented in this review article. Applications of this method in physiology, for
      research into somatosensory and hearing perception, and also in clinical medicine
      for the diagnosis of neurological, dermatological and hearing disorders involving
      changes in perception of sensations different from normal, are discussed. It is
      proposed that the main effective factor of focused ultrasound as a stimulus of
      neural structures is a mechanical one. Such a mechanical effect could produce a
      change in membrane potential resulting in the stimulation of neural structures,
      which is related to the origin of tactile, thermal and hearing sensations. The
      direct action of sign-altering ultrasonic oscillations during the use of
      comparatively long ultrasound stimuli could possibly be the main effective factor
      for the induction of pain sensations and can also change the thresholds of other
      sensations (thermal, hearing and so forth).

PMID- 8735529
TI  - Potential adverse effects of high-intensity focused ultrasound exposure on blood
      vessels in vivo.
AB  - The aim of the study was to evaluate the potential adverse effects of high
      intensity ultrasound exposure on blood vessels during noninvasive focused
      ultrasound surgery. A hydraulic MR-compatible positioning device was used to
      manipulate a focused ultrasound transducer (frequency 1.49 MHz, f-number = 0.8)
      in an MRI scanner. The system was used to sonicate a branch of the femoral artery
      and vein of 19 rabbits (26 thighs) in vivo at intensity levels above the
      threshold for transient cavitation; i.e., between 4400 and 8800 W cm-2 with
      multiple 1 s pulses stepped across the vessels (step size = 0.7 mm). The vessels
      were located and followed by MR angiography. In 13 rabbits, x-ray angiograms were
      also performed after the animals were euthanized. The results demonstrated that
      the 1 s high-intensity exposures caused the arteries to constrict at all exposure
      levels tested. At the intensity of 5800 W cm-2 and above, the MRI angiogram
      immediately after the sonications showed no flow. The x-ray angiograms (1-2 h
      later) showed that the blood vessels were open, but constricted to about 50% or
      less of their diameter. Both the MR and x-ray angiograms showed that the vessel
      diameters relaxed toward their initial diameter during the first week after
      sonication. In five cases, hemorrhage or vessel rupture was caused by the
      sonication. This study demonstrates that short, high-intensity focused ultrasound
      exposure can cause vessel spasm and hemorrhage when transient cavitation is
      present. This condition should be avoided during noninvasive focused ultrasound
      surgery.

PMID- 8735530
TI  - Perfusion corrections for ultrasonic heating in nonperfused media.
AB  - The linear bio-heat transfer equation proposed by Pennes is widely used to
      predict temperature rise in perfused media. In this article, a mathematical
      relationship between the predicted temperature increase under perfused and
      nonperfused conditions is derived based on an analysis of the Pennes equation.
      The perfused temperature at time t and position r, Tperf(r,t) can be calculated
      from the unperfused temperature history Tunperf(r,t) and the time constant for
      perfusion, tau: [formula: see text] When the full nonperfused temperature history
      is not available, a simpler approximate method of estimating the perfused
      temperature is also suggested, requiring only a knowledge of the time constant
      for perfusion. Results are given showing the effects of perfusion after different
      exposure times for a range of beamwidths and perfusion time constants.

PMID- 8735531
TI  - Effects of shadowing on the time-intensity curves in contrast echocardiography: a
      phantom study.
AB  - Literature states that the inability of myocardial contrast echocardiography to
      assess differences in flow between regions could be related to myocardial
      shadowing. In this study, we evaluate this effect on the time-intensity curves.
      In a perfusion phantom, shadowing was induced by high concentrations of a
      contrast agent (approximately 1 x 10(8) bubbles/mL), and evaluated for different
      flows (50-270 mL/min). The high concentration resulted in an increase of the
      video-intensity in regions of interest close to the transducer (2 mm) and a
      marked reduction in remote areas (20 mm). The peak intensity of the time
      intensity curves did not correlate with flow (range r = 0.1, 0.37), while the
      inverse area under the curve correlated strongly (r = 0.98). The inverse curve
      width and the decay after peak intensity also correlated excellently with flow (r
      = 0.99 and range r = 0.97, 0.99). We opt for the decay as transmural flow
      indicator using contrast echocardiography, since this parameter is least affected
      by shadowing.

PMID- 8735532
TI  - Spatial compounding in ultrasonic imaging using an articulated scan arm.
AB  - A spatial compounding system has been designed to improve the quality of B-mode
      echographic images. It consists of constructing an improved image from the
      combination of several different images of the same cross-sectional plane. The
      "final" image is constructed by the registration and the superposition of the
      "original" images. For this, the relative position in the space of the original
      images has to be known. The use of a localization articulated arm, on which the
      ultrasonic probe is fixed, makes this possible. The main advantages of the
      technique are, on one hand, the elimination of the acoustic shadows following a
      strong reflector structure and, on the other hand, the reduction of the speckle
      generated in echographic images. The method of reconstruction has been validated
      on agar gel phantoms and provides good accuracy. In vivo experiments on human
      beings have also been performed. Acoustic shadows caused by bones in cross
      sectional images of the thigh and the arm are eliminated. All the contours of the
      femur and humerus can be observed in the final images. The reduction of speckle
      is shown in kidney images and the signal-to-noise ratio improvement is quantified
      as a function of the number of images involved in the reconstruction.

PMID- 8735533
TI  - Computation of a location shift between two subsequent intra vascular ultrasound
      registrations by cross-correlation analysis of the lumen area functions.
AB  - For longitudinal studies on atherosclerosis and restenosis after angioplasty by
      intravascular ultrasound (IVUS), it is essential that repeated studies are
      performed at exactly the same location along an arterial section. In human
      femoral arteries, lumen and plaque area functions of two subsequent IVUS pullback
      maneuvers were compared by cross-correlation analysis. In cross-correlation
      analysis of two functions with equal abscissa values, the data sets are
      repetitively correlated after incremental shifts of the two functions along the
      abscissa. This results in multiple correlation coefficients with a maximum at the
      relative position where the two functions show the closest match. In group A (12
      patients), both pullbacks were performed after angioplasty and in group B (17
      patients) one pullback was performed before angioplasty and the second
      immediately after angioplasty. In group A, cross-correlation showed a shift
      between lumen area functions of 5 mm in one patient and no shift in the other
      patients. Maximum correlation coefficients in group A ranged from 0.644 to 0.978.
      Four patients from group B showed shifts from 2.5 to 35 mm. Maximum coefficients
      were significantly smaller than in group A: 0.259-0.864 (p < 0.01). Plaque area
      functions in group B showed higher correlations (0.468-0.862, p = 0.034) and only
      two shifts. Cross-correlation of lumen and plaque area functions may be used to
      compute location shifts between two subsequent IVUS registrations and to correct
      such shifts.

PMID- 8735534
TI  - Simulation of ultrasonic imaging with linear arrays in causal absorptive media.
AB  - Rigorous and efficient numerical methods are presented for simulation of acoustic
      propagation in a medium where the absorption is described by relaxation
      processes. It is shown how FFT-based algorithms can be used to simulate
      ultrasound images in pulse-echo mode. General expressions are obtained for the
      complex wavenumber in a relaxing medium. A fit to measurements in biological
      media shows the appropriateness of the model. The wavenumber is applied to three
      FFT-based extrapolation operators, which are implemented in a weak form to reduce
      spatial aliasing. The influence of the absorptive medium on the quality of images
      obtained with a linear array transducer is demonstrated. It is shown that, for
      moderately absorbing media, the absorption has a large influence on the images,
      whereas the dispersion has a negligible effect on the images.

PMID- 8735535
TI  - Amplitude, isobar and grey-scale imaging of ultrasonic shadows behind rigid,
      elastic and gaseous spheres.
AB  - The theory of wave reflection from spherical obstacles was applied for
      determination of the cause of the shadow created by plane wave pulses incident on
      rigid, steel, gaseous spheres and on spheres made of kidney stones. The spheres
      were immersed in water which was assumed to be a tissue-like medium. Acoustic
      pressure distributions behind the spheres with the radii of 1 mm, 2.5 mm and 3.5
      mm were determined at the frequency of 5 MHz. The use of the exact wave theory
      enabled us to take into account the diffraction effects. The computed pressure
      distributions were verified experimentally at the frequency of 5 MHz for a steel
      sphere with a 2.5-mm radius. The experimental and theoretical pulses were
      composed of about three ultrasonic frequency periods. Acoustic pressure
      distributions in the shadow zone of all spheres were shown in the amplitude
      axonometric projection, in the grey scale and also as acoustic isobar patterns.
      Our analysis confirmed existing simpler descriptions of the shadow from the point
      of view of reflection and refraction effects; however, our approach is more
      general, also including diffraction effects and assuming the pulse mode. The
      analysis has shown that gaseous spherical inclusions caused shadows with very
      high dynamics of acoustic pressures that were about 15 dB higher in relation to
      all the other spheres. The shadow length, determined as the length at which one
      observes a 6-dB drop of the acoustic pressure, followed the relation r-6dB =
      3.7a2/lambda with the accuracy of about 20% independent of the sphere type.
      lambda denotes the wavelength and a the sphere radius. Thus, a theoretical
      possibility of differentiating between gaseous and other inclusions and of
      estimation of the inclusion size in the millimeter range from the shadow was
      shown. The influence of the frequency-dependent attenuation on the shadow will be
      considered in the next study.

PMID- 8735536
TI  - Diameter and compliance in the human carotid artery--variations with age and sex.

PMID- 8735537
TI  - Treatment of intrasynovial infection with gentamicin-impregnated
      polymethylmethacrylate beads.
AB  - Gentamicin-impregnated polymethylmethacrylate beads were used in the treatment of
      infective synovitis in 12 horses and 10 cattle. They had either proved refractory
      to standard treatments (lavage, debridement, joint drainage and systemic
      antibiotics) or had evidence of osteomyelitis adjacent to a synovial cavity. All
      the animals were severely lame. All the cattle and six of the horses had
      radiological evidence of osteomyelitis in communication with a synovial cavity.
      The beads were placed intrasynovially under general anaesthesia and left in place
      for 14 days. One horse and one calf were euthanased owing to continued infective
      arthritis. The infection was eliminated from the other 20 cases and six of the
      horses returned to full athletic use. Eight of nine calves with E-type infective
      arthritis and osteomyelitis returned to their intended food production or
      breeding programmes.

PMID- 8735538
TI  - A survey of the behavioural characteristics of pure-bred dogs in the United
      Kingdom.
AB  - One-hundred-and-twelve small animal veterinarians and 56 dog care professionals
      were asked to rate the behavioural characteristics of 49 breeds of dog, and to
      compare males and females by means of a 13-point questionnaire. From their
      replies, factor analysis was used to extract three underlying traits, labelled
      aggressivity, reactivity and immaturity. On the basis of these traits, eight
      groups of breeds were derived. Membership of these groups did not correspond
      exactly with any of the four existing breed classification systems (Megnin, the
      Federation Cynologique International, ancient breeds and Kennel Club of Great
      Britain), but significant differences between Kennel Club groups were found on
      all three traits. Male dogs were rated higher than females on both aggressivity
      and immaturity; the components of reactivity were also rated higher in males,
      apart from the demand for affection which was rated higher in females. Females
      were also considered easier to train than males.

PMID- 8735539
TI  - Treatment of sarcoptic mite infestation and mite hypersensitivity in pigs with
      injectable doramectin.
AB  - Thirty-two pigs were infested experimentally with Sarcoptes scabiei var suis and
      allocated randomly to a medicated group (injected intramuscularly with 300
      micrograms doramectin/kg) or an unmedicated group (injected intramuscularly with
      1 ml saline/33 kg). They were observed daily for 15 minutes for signs of
      pruritus, and the ear lesions were assessed and skin scrapings examined for mites
      on days 7, 14, 21 and 28 after treatment. In the 16 pigs treated with doramectin
      the ear lesions resolved completely within 14 days, no mites were recorded on 15
      of them on day 7 or on any of them on days 14, 21 and 28; pruritus was greatly
      reduced from day 7 onwards (range 0 to 0-62 rubbing episodes per pig per day) and
      papular skin lesions were absent from 15 of the pigs at slaughter on day 28. In
      comparison, the ear lesions in the 16 unmedicated pigs failed to resolve in 15 of
      them. Mites were present on 15 of them at different times during the experiment;
      the numbers of rubbing episodes ranged from 0.88 to 4.65 per pig per day and all
      the pigs had papular skin lesions at slaughter. In the unmedicated pigs, both the
      degree of pruritus and the presence and severity of papular skin lesions at
      slaughter were greater in those with zero or low mite counts than in those with
      high mite counts.

PMID- 8735540
TI  - Ivermectin-moxidectin side resistance by Ostertagia species isolated from goats
      and passaged to sheep.

PMID- 8735541
TI  - Pelodera dermatitis in sheep.

PMID- 8735542
TI  - Black hair follicular dysplasia in a tricolour Jack Russell terrier.

PMID- 8735543
TI  - The BSE crisis.

PMID- 8735544
TI  - Post-hibernation anorexia in tortoises.

PMID- 8735545
TI  - The effect of formaldehyde, hydrogen peroxide and genetic detoxification of
      pertussis toxin on epitope recognition by murine monoclonal antibodies.
AB  - The effect of detoxification of pertussis toxin (PT) for vaccine usage by either
      genetic manipulation, hydrogen peroxide or formaldehyde treatment on epitope
      recognition by a large collection of murine monoclonal pertussis toxin antibodies
      (PT MAbs) was assessed in a solid-phase and a soluble phase enzyme-linked
      immunosorbent assay (ELISA). The MAb binding patterns were found to be different
      in the two assays as the immobilization step appeared to cause conformational
      alterations in the native as well as the toxoided forms of PT. According to the
      solid-phase ELISA, genetic, hydrogen peroxide and 0.35% formaldehyde
      detoxification of PT resulted in reduced epitope binding in 2.9, 31.4 and 78.1%
      of the MAbs, respectively. In the soluble-phase ELISA, in which the MAbs were
      allowed to react with the toxoids or native toxin in solution, the percentages of
      MAbs showing decreased binding activity were 9.1, 50.0 and 71.4%, respectively.
      Stabilization of native PT and the genetically inactivated PT by 0.035%
      formaldehyde reduced the epitope binding activity in 50.0 and 8.7% of the MAbs,
      respectively. Increased antibody binding in the soluble-phase ELISA was observed
      in some of the toxoids: this ranged from 0% in the 0.35% formaldehyde-treated PT
      to 13.6% in the hydrogen peroxide-treated and 27.3% in the genetically detoxified
      PT. Regarding the effects of detoxification on epitopes recognized by PT
      neutralizing MAbs in the soluble-phase ELISA, we found that treatment of PT with
      either 0.035%, 0.35% formaldehyde or hydrogen peroxide induced impairment of
      epitope binding in 72.7, 81.8 and 45.5% of the MAbs, respectively. In the
      genetically inactivated PT, the epitopes recognized by the neutralizing MAbs
      either appeared to remain intact or to show increased MAb binding activity. The
      epitope-binding patterns of several PT MAbs with mouse-protective properties
      varied considerably and were shown to be dependent on the detoxification
      procedure employed. The relevance of epitope alterations on PT as a vaccine
      component is discussed. The results of the present study may have important
      implications for future quality assessment of PT for use in acellular pertussis
      vaccines.

PMID- 8735546
TI  - The N-terminal 303 amino acids of the human cytomegalovirus envelope glycoprotein
      B (UL55) and the exon 4 region of the major immediate early protein 1 (UL123)
      induce a cytotoxic T-cell response.
AB  - We reported earlier that an adenovirus (Ad) recombinant expressing the full
      length human cytomegalovirus (HCMV) glycoprotein B (gB) gene induces gB-specific
      cytotoxic T lymphocyte (CTL) responses in CBA (H-2k) mice (Berencsi et al., J.
      Gen. Virol. 74, 257-2512, 1993). Here we show that mice immunized with Ad
      recombinant viruses expressing truncated forms of the gB gene containing the
      first 700 (Ad-700), 465 (Ad-465) or 303 (Ad-303) amino acids of gB or an Ad
      construct containing exon 4 (E4) of the HCMV immediate early 1 (IEI) gene (Ad-IEI
      (E4)) demonstrate HCMV-specific CTL responses. These data suggest the importance
      of the first 303 amino acids of the gB polypeptide and the IEI E4 product in
      designing a vaccine to induce anti-HCMV CTL responses.

PMID- 8735547
TI  - Comparative efficiency of simple lipopeptide constructs for in vivo induction of
      virus-specific CTL.
AB  - We have previously shown that virus-specific CTL responses can be elicited in
      vivo by injecting, without adjuvant, 12-40 amino acid-long peptides, modified in
      C-terminal position by a simple lipidic amino acid. In this paper, we have
      studied the chemical accessibility, and the ability to induce in mice a CTL
      response, of a series of lipopeptides derived from the HIV-1 env (312-327) or
      (302-335) sequences. We showed that a single modification of these peptides by a
      lipidic amino acid, preferably in C-terminal position, results in the ability to
      reproducibly induce, without adjuvant, a relevant CTL response. No clear
      discrimination appeared concerning the nature of the lipidic modification. Our
      findings indicate that modification of a relatively long peptide by a N epsilon
      palmitoyl-L-Lysylamide can be achieved by conventional methods of synthesis and
      characterization, offering the possibility to develop low-cost synthetic vaccines
      in models in which the CTL component is of importance.

PMID- 8735548
TI  - Yeast expressing hepatitis B virus surface antigen determinants on its surface:
      implications for a possible oral vaccine.
AB  - The two major hydrophilic regions of the hepatitis B virus surface antigen
      (HBsAg) have been expressed in the outer mannoprotein layer of the cell wall of
      "Bakers Yeast", Saccharomyces cerevisiae, by fusing them between the yeast
      invertase signal sequence and the yeast alpha-agglutinin carboxyterminal cell
      wall anchoring sequence. The fusion protein contained most of the preS sequences,
      including the hepatocyte receptor, and part of the S sequence including the "a"
      determinant, and was expressed from multiple genomic copies (MIRY) using the
      constitutive PCK promoter. Immunofluorescence studies showed that the fusion
      protein was detectable at the cell surface and was stably expressed at a
      relatively high level. Intraperitoneal immunization of mice revealed a very weak
      response against the S region, and a high response against yeast itself. It is
      proposed that increasing the amount of the antigen and reducing the number of
      native cell wall proteins, might lead to a yeast that is usable as a safe and
      cheap live oral vaccine.

PMID- 8735549
TI  - What is an acceptable delay in rabies immune globulin administration when vaccine
      alone had been given previously?
AB  - Rabies immune globulins (RIG) are not always available. Rabies-exposed patients
      often present to medical centers, particularly in canine rabies infested regions,
      after a vaccine series has been started without immune globulin administration.
      It is known that rabies immune globulin can result in suppression of the
      neutralizing antibody response which usually yields detectable antibodies by day
      7. We have shown that it can be administered with a delay of up to 5 days after
      the start of vaccine treatment without significant antibody suppression within
      the first month. This study utilized the WHO approved multisite Thai Red Cross
      intradermal postexposure regimen. Effective use of rabies immune globulin in
      severe and multiple wounds, particularly in small children, may require dilution
      of the RIG in normal saline to provide a volume adequate for infiltration of all
      wounds.

PMID- 8735550
TI  - Induction of pneumococcal polysaccharide-specific mucosal immune responses by
      oral immunization.
AB  - Liposome and cholera toxin (CT) are considered to be effective antigen delivery
      vehicles and adjuvants for mucosal vaccines. The effect of these antigen delivery
      systems on adjuvant responses to mucosally administered pneumococcal
      polysaccharide (Pnup) was investigated in this study. Both mucosal (e.g. oral)
      and systemic (i.p.) immunization of mice with purified preparations of Pnup type
      23F induced antigen-specific IgM responses in sera. Interestingly, oral
      immunization of as little as 10 micrograms of Pnup type 23F was sufficient to
      induce systemic IgM responses. Pnup-specific IgM antibodies peaked by day 7 and
      no booster responses were evident after a second dose on day 14. In order to
      examine whether IgG and IgA Pnup-specific immune responses are induced by mucosal
      immunization, the mucosal adjuvant CT was mixed with Pnup type 23 as an oral
      vaccine. Co-oral administration of CT and Pnup type 23F resulted in the induction
      of Pnup-specific faecal IgA antibodies. These results were confirmed by detecting
      antigen-specific IgA-spot-forming cells in mononuclear cell suspensions prepared
      from the intestine of immunized mice. These findings suggest that oral
      immunization with Pnup in the presence of mucosal adjuvants, such as CT, could
      induce Pnup-specific IgA responses whereas Pnup alone did not. In an attempt to
      further enhance antigen-specific antibody responses, Pnup type 23F was
      encapsulated in liposomes and used as mucosal vaccine. However, immunogenicity of
      Pnup was not improved.

PMID- 8735551
TI  - Molecular size characterization of Haemophilus influenzae type b polysaccharide
      protein conjugate vaccines.
AB  - Current vaccines against Haemophilus influenzae type b (Hib) consist of capsular
      polysaccharide, polyribosylribitol phosphate (PRP), chemically conjugated to a
      carrier protein. The stability of the conjugate is essential for vaccine
      efficacy, as the target population for this vaccine includes infants, who do not
      mount an immune response to free polysaccharide vaccines. A method has been
      developed for determining structural stability and batch-to-batch consistency of
      Hib vaccines by the application of fast protein liquid chromatography (FPLC).
      This FPLC method is fast, reproducible, and can be used to evaluate single human
      doses of Hib vaccines. We have shown that the FPLC elution profiles provide a
      suitable indicator of vaccine stability under normal and degradative conditions.
      The method may also be applicable to other conjugate vaccines such as
      meningococcal and pneumococcal protein-polysaccharide conjugates.

PMID- 8735552
TI  - Suppression of virus burden by immunization with feline immunodeficiency virus
      Env protein.
AB  - Whole inactivated virus (WIV) vaccines derived from the FLA cell line protect
      cats against challenge with feline immunodeficiency virus (FIV). To discover
      whether the protective effects of WIV could be reproduced by the isolated Env
      component, either WIV or immunoaffinity-purified FIV gp120 from the FL4 cell line
      was administered to cats. Although both vaccines induced high levels of virus
      neutralizing antibodies, purified Env was much less effective than WIV in
      protecting cats against viraemia. However, reduced virus load in PBMCs was
      evident in all Env-immunized cats compared to controls. Analyses of antibody
      responses to bacterial expression products of FIV Env, which were high in Env
      immunized cats but low in animals receiving the WIV vaccine, suggested that the
      partially denatured, monomeric Env induces a less effective antiviral immune
      response than WIV. Hence, the superior immunogenicity of WIV may be due to the
      presentation of the native oligomeric structure of Env on virions.

PMID- 8735553
TI  - Comparison of adjuvant formulations for cytotoxic T cell induction using
      synthetic peptides.
AB  - We have investigated the capacity of synthetic peptides delivered in different
      adjuvant formulations to induce cytotoxic T lymphocyte (CTL) responses to a class
      I H-2Kd-restricted Plasmodium berghei circumsporozoite epitope, CS 252-260. Using
      three immunogen formulations: soybean emulsion; Montanide ISA720; and lipopeptide
      (P3-CS), we first evaluated the effects of immunization routes on CTL induction.
      No CTL response was induced in mice immunized s.c. or i.p. with CS peptide
      formulated in soybean emulsion. In contrast, immunization with lipopeptide P3-CS
      either s.c. or i.p. effectively primed for CTL. Interestingly, CS peptide
      emulsified in Montanide ISA720 induced a CTL response only when delivered s.c.
      and not i.p., indicating the critical influence of immunization routes on CTL
      induction. We then compared the effectiveness of eight adjuvant formulations to
      induce CTL response following a single s.c. immunization. Notably, lipopeptide P3
      CS and CS peptide admixed with P3 or POE lipid molecules stimulated a vigorous
      CTL response. However, only mice immunized with P3-CS and CS peptide admixed with
      P3 molecule generated long-lived CTL which persisted in vivo for 5 months. Thus,
      based on a simultaneous comparison of the different adjuvant formulations, we
      demonstrated that the conjugated and unconjugated P3 lipopeptides were the most
      effective immunogens for eliciting primary and memory CTL in mice.

PMID- 8735554
TI  - Absence of protein 2C from clarified foot-and-mouth disease virus vaccines
      provides the basis for distinguishing convalescent from vaccinated animals.
AB  - We have recently reported that cattle and pigs which have been vaccinated against
      foot-and-mouth disease can be distinguished from convalescent animals by the
      absence of antibodies to viral non-structural protein 2C (Lubroth and Brown, Res.
      Vet. Sci., 1995, 59, 70-78(1)). In this study, we show that the absence of 2C
      antibodies from the sera of vaccinated animals can be explained by the
      association of this viral protein with cellular debris which is separated from
      the virus harvest prior to inactivation of the supernatant for vaccine
      production. This serological marker can be of great value in countries where the
      disease occurs or in the veterinary regulatory arena when livestock are
      transported across borders, since it can be used to identify convalescent,
      persistently infected animals and vaccinates exposed to wild-type virus variants
      which have infected the vaccinated animals.

PMID- 8735556
TI  - Immunogenicity, efficacy and serological correlate of protection of Salmonella
      typhi Vi capsular polysaccharide vaccine three years after immunization.
AB  - The protective efficacy and immunogenicity of Vi capsular polysaccharide vaccine
      against typhoid fever was measured 3 years after its administration in a double
      blind randomized trial. Vaccine efficacy was not significantly different during
      each year of the trial and was 55% (95% CI: 30-71%) over the 3 year period. In a
      case-control study at 3 years after vaccination, recipients of Vi had higher
      levels of Vi antibodies than controls, as measured by radio-immunoassay (GMT 1.28
      vs 0.76 microgram ml-1, P = 0.0004) and by passive haemagglutination assay (GMT
      10.46 vs 3.52, P = 0.0001). The serological correlate of protection has been
      estimated using the relative risks of typhoid fever in the 2 groups and the
      relative ratio of antibody levels. The estimated protective level is 1 microgram
      ml-1 suggesting that at a mean age of 9 years, 64% of vaccinates and 40% of
      controls had protective antibody against typhoid fever in this endemic area.

PMID- 8735555
TI  - Human safety and immunogenicity of a canarypox-rabies glycoprotein recombinant
      vaccine: an alternative poxvirus vector system.
AB  - Avian poxvirus recombinants undergo abortive replication in nonavian cells, yet
      can achieve expression of extrinsic gene products. Canarypox-vectored vaccines
      have been innocuous and immunogenic in several mammalian species. ALVAC-RG, a
      canarypox recombinant expressing the rabies glycoprotein gene, was inoculated
      intramuscularly into adult volunteers on days 0, 28, and 180. Sequential cohorts
      received 10(3.5), 10(4.5), and 10(5.5) 50% tissue culture infective doses
      (TCID50); additional volunteers received the standard human diploid cell rabies
      vaccine (HDCV) on the same schedule. Reactogenicity of ALVAC-RG was minimal. The
      lowest dose of ALVAC-RG induced little antibody to rabies virus by ELISA or rapid
      fluorescent focus inhibition test (RFFIT), but 10(4.5) and 10(5.5) TCID50 doses
      elicited significant responses in both assays. All recipients of 10(4.5) and
      10(5.5) TCID50 of ALVAC-RG attained RFFIT values above the presumed protective
      level. Canarypox-specific immune responses did not inhibit boosting of rabies
      specific antibodies by the day 180 dose of ALVAC-RG. T cell proliferation in
      response to inactivated rabies virus in vitro was similar in HDCV and ALVAC-RG
      recipients after the first and second doses, although HDCV yielded superior
      results after the third dose. ALVAC-RG was safe in humans, induced functional
      antibody to rabies glycoprotein, elicited cellular responses to rabies virus, and
      could be used successfully for booster dosing at a 6 month interval.

PMID- 8735557
TI  - A simple, quantitative, reproducible avidin-biotin ELISA for the evaluation of
      group B streptococcus type-specific antibodies in humans.
AB  - Type-specific antibodies to the capsular polysaccharides (CP) of group B
      Streptococcus (GBS) are protective. Historically, the radioactive antigen-binding
      assay (RABA) has been used to determine GBS antibody levels. This method measures
      total immunoglobulin and employs the use of radioactive materials. We have
      developed an avidin-biotin ELISA that is less hazardous and is able to measure
      GBS Ia, Ib, II or III CP specific IgG. To avoid inconsistent binding to the
      plate, the CPs from GBS Ia, Ib, II and III were derivatized using adipic acid
      dihydrazide (ADH) and subsequently biotinylated without altering their antigenic
      epitopes and bound to avidin coated plates. Plasma from three different human
      subjects immunized with a tetravalent CP vaccine were used to prepare IgG
      references for Ia, II and III, respectively, thus rendering the assay
      quantitative for those types. The assay is able to detect nanograms per
      milliliter of GBS Ia, Ib, II or III specific antibody. This method is
      reproducible, sensitive and correlates with RABA by 76%.

PMID- 8735558
TI  - Safety and immunogenicity of a tetravalent group B streptococcal polysaccharide
      vaccine in healthy adults.
AB  - Proposed strategies for prevention of neonatal group B streptococcal (GBS)
      infection have included active immunization of pregnant women and passive
      immunization of high-risk infants with hyperimmune GBS globulin derived from
      vaccinated plasma donors. To explore the feasibility of a program for generating
      hyperimmune GBS globulin, we evaluated the safety and immunogenicity of a
      candidate multivalent GBS vaccine containing purified polysaccharide from types
      Ia, Ib, II, and III among subjects most likely to develop an immune response
      following vaccination, i.e. those with pre-existing antibody to GBS. Thirty
      volunteers prescreened for serum antibody to type III GBS were immunized with a
      single subcutaneous injection of vaccine containing either 10, 25, or 50
      micrograms of each polysaccharide type (Group 1). An additional ten volunteers
      prescreened for antibody to type Ia were vaccinated with the 50 micrograms dose
      (Group 2). Vaccination was generally well tolerated with minor reactions
      occurring in 27% of subjects. Using a quantitative enzyme-linked immunosorbent
      assay (ELISA), the seroconversion rates (> or = fourfold rise) and geometric mean
      antibody concentration (GMC in microgram IgG ml-1) 6 weeks after vaccination in
      Group 1 to type Ia, II, and III were 33% (GMC 5.2), 17% (GMC 3.6), and 70% (GMC
      43.4), respectively. Quantitative titers were not available for type Ib, but a
      fourfold rise in ELISA units was seen in 13% of subjects. In Group 2,
      seroconversion rates to type Ia and III were 90% (GMC 73.4) and 40% (GMC 22.2),
      respectively. No significant dose-response effect was detected. Combined analysis
      of Groups 1 and 2 demonstrated that subjects with prevaccination antibody
      concentrations > 2 micrograms IgG ml-1 had significantly higher type-specific
      antibody concentrations following vaccination compared with subjects possessing
      lower levels of antibody before immunization. We conclude that our tetravalent
      GBS polysaccharide vaccine is safe but only modestly immunogenic in healthy
      seropositive adults. More potent vaccines will be required for public health use.

PMID- 8735559
TI  - An investigation into the immunogenicity of a GnRH analogue in male rats: a
      comparison of the toxicity of various adjuvants used in conjunction with GnRH
      glycys.
AB  - Immunization of male Copenhagen Fischer rats with a gonadotrophin releasing
      hormone (GnRH) analogue, conjugated to PPD resulted in high levels of antibody
      being produced which disrupted gonadal function in male rats. The antibody
      reduced serum testosterone levels and subsequently suppressed spermatogenesis.
      Alternatives to Freund's adjuvant were tested, namely, aluminium hydroxide and
      non-ionic surfactant vesicles (NISV). The study showed that aluminium hydroxide
      was as effective as Freund's adjuvant and less toxic, in both BCG and non-BCG
      primed animals. However, NISV were completely non-toxic and most effective in
      conjunction with BCG priming. The data obtained showed that NISV have the
      potential to be used as an alternative to FCA and aluminium hydroxide-based
      adjuvants.

PMID- 8735560
TI  - Report on management of renal failure in Europe, XXV, 1994 end stage renal
      disease and dialysis report. The EDTA-ERA Registry. European Dialysis and
      Transplant Association-European Renal Association.

PMID- 8735561
TI  - Report on management of renal failure in Europe, XXV, 1994. The child-adult
      interface. The EDTA-ERA Registry. European Dialysis and Transplant Association
      European Renal Association.

PMID- 8735562
TI  - Transplantation Report. 1: renal transplantation in recipients aged 60 years or
      older at time of grafting. The EDTA-ERA Registry. European Dialysis and
      transplant Association-European Renal Association.

PMID- 8735563
TI  - Transplantation Report. 2: Pre-emptive renal transplantation in adults aged over
      15 years. The EDTA-ERA Registry. European Dialysis and Transplant Association
      European Renal Association.
AB  - Between 1985 to 1992, 2545 renal transplantation (RTx) were performed as pre
      emptive grafts in adults. This procedure represented 7.2% of first RTx for
      patients starting first renal replacement therapy (RRT) during this period, 6.1%
      of RTx performed in 1992 and 5.6% of all RTx ever performed and reported to the
      EDTA Registry. The procedure is more frequent in cases of live donor grafts,
      representing one third of pre-emptive RTx. Both 5 year patient and graft
      survivals are unaffected by dialysis duration prior to the first RTx: none in pre
      emptive, < 1 years, 1-5 years or > 5 years. In our personal view, this procedure
      should be developed.

PMID- 8735564
TI  - Transplantation Report. 3: annual end-stage renal disease (ESRD). Demography and
      treatment: application of a mathematic model based on the compartment (kinetic)
      theory. The EDTA-ERA Registry. European Dialysis and Transplant Association
      European Renal Association.

PMID- 8735565
TI  - The effects of central administration of neuropeptide Y on behavior,
      neurotransmitter, and immune functions in the olfactory bulbectomized rat model
      of depression.
AB  - The effects of subchronicly administered neuropeptide Y (NPY)
      intracerebroventricularly on behavioral, neurochemical, and immunological
      parameters were examined in sham operated and olfactory bulbectomized (OB) rats.
      In the untreated OB rats, an increase in ambulation, rearing, grooming, and
      defecation scores was found in the novel stressful environment of an "open
      field." Following 7 days of NPY administration, these behaviors were largely
      attenuated. In the elevated plus-maze apparatus, OB rats showed an increase in
      the number of entries into the open arms and time spent on the open arms compared
      with sham operated animals; NPY had no significant effect on the behavior of
      either sham operated or OB animals in this test. A decrease in the NA
      concentration was found in the amygdloid cortex of OB rats. NPY infusion
      significantly increased the NA concentration in amygdala, reduced 5-HIAA but
      increased 5-HT concentrations in the hypothalamus, and increased the dopamine
      level in the hippocampus. NPY administration also reversed the suppression of
      lymphocyte proliferation in the OB rat. However, the changes in the differential
      white blood cell count and the elevated phytohemagglutinin-induced
      chemiluminescence of mononuclear cells in the OB were not altered by NPY. These
      results suggest that NPY may have a modulatory effect on some behavioral,
      neurotransmitter, and immune aspects of the OB rat model of depression.

PMID- 8735566
TI  - Regulation of NK activity by the administration of bromocriptine in haloperidol
      treated mice.
AB  - Haloperidol (HPD) is a dopamine receptor blocker and a major causative agent of
      neuroleptic malignant syndrome. To investigate the influence of HPD on immune
      responsiveness, the natural killer (NK) cell activity of mice was examined after
      intraperitoneal administration of HPD for 5 days. NK cell activity was markedly
      decreased without a depletion of NK cells. Bromocriptine (BROMO), which is used
      for the treatment of neuroleptic malignant syndrome, also decreased NK cell
      activity. The suppressive effect on NK cell activity was inhibited by injecting
      both HPD and BROMO simultaneously. Serum levels of prolactin (PRL) decreased
      after BROMO injection, although serum PRL level was not decreased after the
      combined administration of HPD and BROMO agents. The reduction of NK cell
      activity caused by BROMO and by HPD was prevented by the co-injection of PRL and
      by a beta-adrenergic blocker, respectively. These results indicate that HPD
      decreases NK cell activity in a PRL-independent manner and that BROMO decreases
      it via PRL reduction. It seems that the PRL-independent suppressive effect of HPD
      on NK cells, which is neutralized by BROMO, is mediated by splenic sympathetic
      function via the beta-adrenergic receptor system. Therefore, BROMO helps to
      alleviate the depressed NK cell activity caused by HPD therapy.

PMID- 8735567
TI  - Surgical and psychological stressors differentially affect cytolytic responses in
      the rhesus monkey.
AB  - Four experiments were conducted in aged rhesus monkeys to investigate how
      physical and psychological stressors influence the lymphocyte cytolytic responses
      against two target cell lines. An initial analysis of the lytic activity of
      various cell subsets against K562 and RAJI target cell lines suggested that both
      CD3+CD8+ and several CD3- subsets were responsible for lysis of the K562 cells.
      The RAJI cell line, in contrast, was killed primarily by CD3-subsets. To explore
      the implications of this differential mediation of lysis, cytolytic activity was
      evaluated after a physical challenge (surgery), a psychological disturbance
      (social separation), and in vitro incubation of lymphocytes with cortisol. The
      minor surgical procedure-laparoscopic examination-resulted in a significant
      decrease in lymphocyte cytolytic responses against both target cells 1 week
      postsurgery. In contrast, psychological disturbance elicited by changes in social
      relations caused a dual response, differentially affecting the lysis of either
      K562 or RAJI cells, dependent upon the type of behavioral reaction. Incubation of
      lymphocytes with cortisol in vitro indicated that lysis of both targets could be
      affected by corticosteroids, but the high concentration required (10(-6) M)
      suggested that the in vivo inhibition of cytotoxicity may not have been mediated
      by adrenocortical activation. Overall, the results highlight the value of
      utilizing multiple target cell systems in the analysis of cytolytic activity,
      especially in studies using nonhuman primates.

PMID- 8735568
TI  - Conditioned immunosuppression in orally immunized mice.
AB  - Mice were given oral immunization after pretreatment with a regimen
      (cyclophosphamide and a novel taste in the drinking water, chocolate milk (CHM),
      which leads to suppression of the antibody response to intravenously administered
      antigens given concurrently with CHM. Following this treatment mice were
      reexposed to CHM and IgM and IgA antibody forming cells (AFC) were measured in
      spleen and Peyer's patch cells. Conditioned immunosuppression of AFC production
      was most marked (> fivefold) for IgA-AFC in Peyer's patch, with effects of lesser
      magnitude for IgM-AFC in Peyer's patch (twofold) and both IgM- and IgA-AFC in
      spleen. Analysis of cytokine production from stimulated Peyer's patch and splenic
      T cells in vitro showed significant decreased production of both IL-2 and IL-4,
      with the latter being the predominant cytokine produced in Peyer's patch cells of
      control animals.

PMID- 8735569
TI  - Catecholamines decrease lymphocyte adhesion to cytokine-activated endothelial
      cells.
AB  - Numerous studies have shown that catecholamines can modulate lymphocyte
      migration. This effect may be mediated in part by modulation of lymphocyte
      endothelial cell interactions, which is dependent on adhesion molecules expressed
      on both of these cells. Our results show that catecholamines decreased T-cell
      binding to IL-1 activated endothelial cells in vitro. The decrease in adhesion
      was not mediated by a change in adhesion molecule expression as LFA-1 and VLA-4
      expression on T-cells and ICAM-1 and VCAM-1 expression on endothelial cells were
      not changed by catecholamine stimulation. T-cells flatten and enlarge the area of
      surface contact as they adhere to endothelial cells. Image analysis of the number
      of T-cells bound and the amount of cell spreading over several time points
      suggests that catecholamines alter the kinetics of T-cell-endothelial cell
      adhesion. These results support the hypothesis that catecholamines can alter
      lymphocyte-endothelial interactions in vivo, which in turn would affect
      lymphocyte migration.

PMID- 8735570
TI  - Interleukin-1 beta reduces daily activity level in male lizards, Sceloporus
      occidentalis.
AB  - In mammals, interleukin-1 (IL-1) mediates many of the behavioral consequences of
      pathogen infection. Other vertebrates show behavioral changes when infected, but
      the neuroendocrine bases of these changes are seldom known. Here we report that
      IL-1 beta alters the daily activity cycle of lizards (Sceloporus occidentalis)
      similar to that seen in lizards infected with malaria. To our knowledge, this is
      the first report of behavioral effects of interleukin in lower vertebrates. Male
      lizards were injected with human IL-1 beta (10 ng/g animal), saline, or nothing
      (control) and the activity level (proportion of lizards above ground) was
      monitored for 48 h. IL-1 beta-injected lizards showed a decrease in activity
      compared to saline-injected and control lizards within 2 h after treatment.
      Activity levels were equivalent among treatment groups during the middle of the
      day (1200-1600 h), but IL-1-treated animals were significantly less active in the
      morning (0800-1200 h) and evening (1600-2200 h). This decrease in activity is
      similar that seen in free-ranging lizards infected with malaria, supporting the
      hypothesis that IL-1 mediates the pathogen-induced alterations to activity
      behavior under natural conditions.

PMID- 8735571
TI  - Self-instructional intervention for teaching generalized problem-solving within a
      functional task sequence.
AB  - Effects of an intervention that combined self-instruction with multiple exemplar
      training on the generalized problem solving of five high school students with
      severe mental retardation were examined. Innovative features of the intervention
      included (a) preteaching self-instruction to proficiency with one exemplar before
      introducing multiple exemplars and (b) embedding problem situations within a
      functional task sequence. Findings indicated that all students learned to perform
      five trained problem responses and five generalized responses while self
      instructing. The self-instructional intervention appeared to decrease training
      time required to self-instruct as well as to decrease variability with which
      participants verbalized their self-instructions.

PMID- 8735572
TI  - Reported communication abilities of individuals with severe mental retardation.
AB  - Little is known about the distribution of communication skills among individuals
      with severe mental retardation. The present study was designed to obtain basic
      descriptive information about the reported expressive communication status and
      other associated sensory and behavioral characteristics of four representative
      samples of this overall population. These samples include both children and
      adults and individuals living in large residential facilities as well as those
      living at home or in smaller, more natural community environments. Results of
      this study, based on completed questionnaires for 211 subjects, revealed a wide
      range of communication abilities in this population, with a significantly larger
      percentage of adults than children communicating at symbolic levels.

PMID- 8735573
TI  - Comparison of sustained and selective attention in children who have mental
      retardation with and without attention deficit hyperactivity disorder.
AB  - Attention deficits have been demonstrated in children with attention deficit
      hyperactivity disorder (ADHD) in the general population, but little is known
      about attention deficits in children with ADHD who also have mental retardation.
      In this investigation, children with ADHD and mental retardation were compared to
      those with mental retardation without ADHD on tasks assessing sustained and
      selective attention. Although children with ADHD and mental retardation made
      fewer correct target detections and more commissions on a vigilance task, no
      compelling evidence emerged for sustained attention deficits. However, evidence
      did emerge that was suggestive of selective attention deficits in these children.
      Results also suggest that girls with mental retardation may be at a higher risk
      for ADHD than are girls in the general population.

PMID- 8735574
TI  - Joint attention and language gains in children with Down syndrome.
AB  - Joint attention and topic initiation in caregiver-child interactions was explored
      in relation to children's language gains over 13 months. Caregivers of 28
      children with Down syndrome spent more time in joint attention and maintained
      more attention to caregiver-selected toys than did caregivers of 17 children with
      typical development. Receptive language gains of children with Down syndrome were
      associated with caregivers maintaining attention to child-selected toys and with
      longer lengths of joint attention. Caregivers redirecting attention away from
      child-selected toys and a greater frequency of joint attention episodes was
      negatively associated with children's language gains. More time spent in joint
      attention and caregivers maintaining attention to mother-selected toys was
      associated with receptive language gains in children who were developing
      typically.

PMID- 8735575
TI  - Self-enhancing effect of social feedback on cognitive task performance.
AB  - The influence of feedback on the cognitive task performance of individuals with
      high and low self-esteem was assessed (Coopersmith Self-Esteem Inventory, Form
      A). A median split technique segregated each group (30 adults with mental
      retardation and 30 MA-matched controls) into high and low self-esteem
      individuals. All subjects performed two memory tasks (easy, difficult) but were
      randomly assigned to only one of three feedback conditions (social, computer, and
      no feedback). Findings indicated that social feedback can alter the normally
      positive relation between self-esteem and cognitive task performance.

PMID- 8735576
TI  - Essential characteristics of self-determined behavior of individuals with mental
      retardation.
AB  - Despite increased emphasis on self-determination for individuals with mental
      retardation, only a few theoretical models have been formulated that specify
      measurable characteristics for the promotion and evaluation of this outcome. We
      propose that self-determination refers to acting as the primary causal agent in
      one's life and making choices and decisions regarding one's quality of life free
      from undue external influence or interference. Self-determined behavior is
      autonomous, self-regulated, based on psychological empowerment, and self
      realizing. We evaluated this definition by asking participants with mental
      retardation to complete various instruments that measured self-determined
      behavior and these essential characteristics. Discriminant function analysis
      indicated that measures of essential characteristics predicted differences
      between groups based on exhibition of self-determined behavior.

PMID- 8735577
TI  - Mortality of people with mental retardation in California with and without Down
      syndrome, 1986-1991.
AB  - Mortality of people with mental retardation receiving services in California was
      examined. The large population (N = 118,653) enabled us to work directly with
      mortality rates at specific ages. Up to about age 35, mortality rates of people
      with Down syndrome were comparable to those of people with mental retardation due
      to other causes. Subsequently, the increase was much more rapid in the group with
      Down syndrome. Mortality rates of individuals with Down syndrome doubled every
      6.4 years compared to 9.6 years for people without Down syndrome. Life tables
      were constructed; the remaining life expectancy of a 1-year-old child with Down
      syndrome with mild/moderate retardation was 55 years and with profound mental
      retardation, 43 years.

PMID- 8735578
TI  - Clomipramine treatment for self-injurious behavior of individuals with mental
      retardation: a double-blind comparison with placebo.
AB  - The efficacy of the serotonin (5-HT) uptake inhibitor clomipramine in the
      treatment of self-injurious behavior (SIB) was tested in individuals with severe
      and profound mental retardation. Six of the 8 subjects who completed a double
      blind, placebo-controlled crossover trial exhibited a clinically significant
      improvement (50% or greater reduction from placebo) in the frequency of SIB.
      Clomipramine treatment was also associated with improvement in SIB intensity,
      frequency of stereotypy and compulsions, teacher ratings of stereotypy and social
      withdrawal, and frequency of staff intervention required for problem behaviors.
      Adverse effects (seizure and tachycardia/agitation) occurred in 2 of the 8
      subjects. These results represent the first controlled trial of a 5-HT uptake
      inhibitor in the treatment of SIB in mental retardation.

PMID- 8735579
TI  - Extrapolated raw scores for the second edition of the Bayley Scales of Infant
      Development.

PMID- 8735580
TI  - Cues to parent involvement in drug prevention and school activities.
AB  - This exploratory study used focus group methods to identify strategies that
      promote parent involvement with young children in an alcohol, tobacco, and other
      drug (ATOD) prevention program. The Health Belief Model (HBM) guided the
      interview process and data analysis. Five focus groups were conducted with low
      income parents and school personnel from two urban elementary schools in
      Lexington, Kentucky. Cues to Action was the most frequent HBM construct expressed
      by both parents and school personnel in regard to ATOD prevention programs and
      general school activities. Enthusiasm for school activities expressed by children
      to their parents was identified as the core cue to parent involvement.
      Transportation, child care, and incentives were the basic requirements for parent
      involvement. Positive attitudes of school personnel, a combination of
      communication strategies, and multiple channels for involvement were major cues
      to parent involvement. Recommendations for involving parents in ATOD prevention
      and general school activities are suggested.

PMID- 8735581
TI  - Is school vision screening effective?
AB  - A population-based cohort of all children entering kindergarten in a three-year
      period (N = 2,938) was followed retrospectively from kindergarten through 12th
      grade to estimate incidence of abnormal school vision screening tests and rates
      of follow-up by community ophthalmologists or optometrists. Overall 28% of
      children had at least one abnormal school vision screening test. Abnormal
      screening with referral increased from 1.2% of five-year-olds to 9.1% of 13-year
      olds. Overall, 91% of children referred had further evaluation by eye care
      professionals. However, visits to an eye care professional often were delayed;
      median time was 0.8 years for children seeing an ophthalmologist and 1.8 years
      for children seeing an optometrist. Results support the continued use of simple
      visual acuity screening in schools. Consideration should be given to screening
      children beyond age 12 and developing methods to increase the rapidity of
      parental response to referral recommendations.

PMID- 8735582
TI  - A peer-led AIDS prevention program for students in an alternative school.
AB  - School-based programs designed to measure health risk behavior and reduce the
      risk of sexually transmitted diseases (STDs) and human immunodeficiency virus
      (HIV) infection have not addressed adequately the needs of adolescents outside of
      main-stream schools. In Florida, these youth represent a sizable proportion of
      the population and have been shown to be at increased risk for acquiring sexually
      transmitted diseases and human immunodeficiency virus. This article describes a
      peer-led STD/HIV intervention for students in a dropout prevention program in
      Dade Country, Florida. Trained peer counselor/educators (PCEs) led schoolwide
      activities and classroom sessions covering STD/HIV information, community health
      resources, communication and negotiation skills, and safer sex strategies.
      Teachers and students rated the PCEs effective in promoting discussion and
      serving as sources of information about AIDS and community health resources.
      Pre/post intervention questionaire results demonstrated an increase in AIDS
      awareness and discussion among students as well as an increase in condom use.
      Based on this social influences approach, peer education appears to be a
      promising health education strategy for students in dropout prevention programs.

PMID- 8735583
TI  - Combating the illusion of adolescent invincibility to HIV/AIDS.

PMID- 8735584
TI  - What in the world?

PMID- 8735585
TI  - Up-regulation of nuclear IGF-I receptor by short term exposure of stilbene
      estrogen, diethylstilbestrol.
AB  - In the present study we report the novel findings that IGF-I receptors are
      present in the nucleus based on the evidence from binding assay, detection of
      receptors by affinity labeling and Western blotting, and localization by
      immunofluorescence. The level of nuclear IGF-I receptors (nIGF-IRs) almost
      doubled in stilbene estrogen (diethylstilbestrol, DES) treated hamster kidneys
      compared to the controls. The binding constants Kd and Bmax of nIGF-IR of
      controls, 22.1 nM and 6.6 nmol/mg protein, respectively, were changed in response
      to DES treatment to 5.3 nM and 16.3 nmol/mg protein (P < 0.001), respectively.
      The enhanced level of IGF-IR in DES-treated nuclei was confirmed by both affinity
      labeling and Western blotting. These data suggest that IGFs may exert their
      biological effect through the IGF-I receptor present in the nucleus. Whether the
      up-regulation of nIGF-IR by exposure to a carcinogenic dose of DES may be a
      factor in the induction of renal cancer in Syrian hamsters, is not clear.

PMID- 8735586
TI  - Local expression of a POU family transcription factor, Pit-1, in the rat
      placenta.
AB  - A pituitary-specific trans-acting factor, Pit-1 regulates transcriptional
      activity of growth hormone (GH) and prolactin (PRL) genes. Pit-1 can bind and
      activate the promoters of human chorionic somatomammotropin (hCS-A) and placental
      GH variants (hGH-V) as well. However, expression of Pit-1 in the rat placenta has
      not yet been elucidated. The present study aims to determine whether the Pit-1
      gene is locally expressed in the rat placenta using reverse transcription
      polymerase chain reaction (RT-PCR), Northern blot and Western blot hybridization,
      in situ hybridization and immunohistochemistry. PCR products were further
      analyzed by Southern hybridization and DNA sequencing. The estimated size of Pit
      1 mRNA in placenta was very similar to that in anterior pituitary (AP). PCR
      products from placenta were exactly the same size with that from AP and confirmed
      as Pit-1-specific by Southern hybridization. The Pit-1 specific sequence was also
      confirmed by sequencing of partial amplification fragments. Immunoreactive 33 kDa
      Pit-1 was present in the placenta as well as in AP. Pit-1 specific mRNA and
      protein were localized in the trophoblast cells of placenta. These data suggest
      that Pit-1 is locally synthesized in the rat placenta and may be involved in the
      regulation of GH- and/or PRL-like gene expression in the placenta.

PMID- 8735587
TI  - Alpha-fetoprotein derived synthetic peptides: assay of an estrogen-modifying
      regulatory segment.
AB  - This study describes the estrogen bioassay of a synthetic peptide fashioned after
      an amino acid sequence from human alpha-fetoprotein (HAFP). The synthetic peptide
      (P149), modeled after a portion of the estrogen binding pocket of rat/human AFP
      chimeras, was produced via F-MOC solid phase chemistry. Bioassay of P149 in the
      estrogen-sensitive immature rodent uterus demonstrated an anti-estrogenic (40-50%
      inhibitory) activity in the 23 h but not the 3-4 h uterine response. In contrast
      to purified HAFP, incubation of the peptide with estrogen was not a prerequisite
      for inhibitory activity. The estrogen-dependent increase in uterine thrombin and
      tissue factor, as determined by an enzymatic esterase assay, was inhibited by 30%
      in rat uterine cytosols. In an in vitro bioassay of estrogen-induced focus
      formation in MCF-7 human breast cancer cultures, focus development was inhibited
      by 70% following peptide exposure. The mechanism of the AFP-derived peptide
      inhibition of estrogen-dependent growth remains to be determined.

PMID- 8735588
TI  - Involvement of a subset of tyrosine kinases and phosphatases in regulation of the
      beta-lactoglobulin gene promoter by prolactin.
AB  - This study used pharmacological intervention to provide support for a role of
      kinases and phosphatases in prolactin transactivation of a milk protein gene. It
      was based on transient cotransfection using a rabbit prolactin receptor
      expression plasmid and a beta-lactoglobulin promoter/CAT reporter construct. In
      cotransfected CHO cells, herbimycin A and tyrphostin, two tyrosine kinase
      inhibitors, were able to decrease the CAT response by over 50%, along with
      tyrosine phosphorylation of cellular proteins, whereas genistein and lavendustine
      were without effect on lactoglobulin transactivation. Orthovanadate, an
      inactivator of tyrosine phosphatases, was able to substitute for prolactin in
      inducing the CAT response. Staurosporine, a non-specific kinase inhibitor, was
      able, when used at low concentrations (10 nM), to augment the prolactin response
      strikingly. Threonine/serine kinases do not appear to be involved early in beta
      lactoglobulin promoter transactivation, since four C-kinase inhibitors and
      okadaic acid a threonine/serine phosphatase inhibitor, were without substantive
      effect. We conclude that specific tyrosine kinases are responsible for most of
      the signal transduction from the prolactin receptor to the beta-lactoglobulin
      gene promoter.

PMID- 8735589
TI  - Gelatinase A secretion and its control in peritubular and Sertoli cell cultures:
      effects of hormones, second messengers and inducers of cytokine production.
AB  - Extracellular matrix components as well as enzymes and enzyme-inhibitors
      controlling the turn-over of these components play an important role in the local
      control of testicular function. Zymographic analysis was used to study the
      secretion and the control of the secretion of gelatinase A (MMP-2) and B (MMP-9)
      by primary cultures of rat Sertoli cells and by subcultures of peritubular cells.
      Data on gelatinase A were complemented by measurement of the corresponding mRNA
      by Northern blot analysis. The agonists investigated included hormones (FSH,
      testosterone), second messengers (dbcAMP, phorbolester and a Ca(2+)- ionophore),
      interleukin-1 beta (IL-1 beta) and inducers of cytokine production (Concanavalin
      A: ConA; lipopolysaccharide: LPS; double stranded RNA: PIC). It is demonstrated
      that Sertoli cells originally secrete both gelatinase A and B. When maintained in
      serum-free medium, however, they rapidly lose the ability to secrete gelatinase
      B. After 3 days of culture gelatinase A remains the only measurable gelatinase in
      both Sertoli and peritubular cell cultures. The production in peritubular cells,
      however, exceeds that in Sertoli cells some 25-fold. This was confirmed by a 30
      fold difference in the level of steady-state gelatinase A mRNA levels. Gelatinase
      A secretion and gelatinase A mRNA were stimulated by ovine FSH in Sertoli cells
      and by dbcAMP and ConA in both Sertoli and peritubular cells. IL-1 beta displayed
      measurable but limited stimulatory effects in both cell types. Interestingly, in
      peritubular cells but not in Sertoli cells, ConA stimulated the production of a
      lower MW species probably representing an activated form of gelatinase A. It is
      concluded that both the amounts of gelatinase A produced, the levels of the
      corresponding mRNA and the regulation differ in cultured peritubular cells and
      Sertoli cells. The lectin concanavalin A is a novel and potent inducer of
      gelatinase A. It resembles cytochalasin D in selectively inducing an activated
      form of gelatinase A in peritubular cells. The mechanism responsible for this
      selective effect warrants further investigation.

PMID- 8735590
TI  - An adenosine derivative cooperates with TSH and Graves' IgG to induce Ca2+
      mobilization in single human thyroid cells.
AB  - Digital video imaging indicated that about 80% of fura-2-loaded single human
      thyroid cells responded to TSH, resulting in an increase in intracellular Ca2+
      concentration ([Ca2+]i). Most of the TSH-sensitive cells further responded to N6
      (L-2-phenylisopropyl)-adenosine (PIA) showing a transient [Ca2+]i rise in a PIA
      dose-dependent manner. Addition of PIA prior to TSH administration had no effect
      or showed only a slight [Ca2+]i increase, but in about 80% of the cells,
      regardless of the response to PIA, the addition of TSH after PIA resulted in a
      higher transient [Ca2+]i response than that in the absence of PIA. Inactivation
      of Gi/G(o) by pertussis toxin (PTX) treatment markedly reduced the effect of PIA
      on TSH action to the level induced by PIA alone. Immunoglobulin fractions
      obtained from two Graves' patients with high TSAb (antibody activity measured by
      cAMP response) activity induced [Ca2+]i increase and cooperated with PIA. Under
      the same conditions, TSH-dependent cAMP accumulation was inhibited by PIA. These
      results suggest that adenosine Ai receptor is expressed in human thyroid cells in
      primary culture as well as in FRTL-5 rat thyroid cells, and that in the presence
      of adenosine. TSH or Graves' IgG signal tends to be directed to the Ca2+ pathway
      in the human thyroid.

PMID- 8735591
TI  - Evidence that heparin binding autocrine factors modulate testosterone production
      by the adult rat Leydig cell.
AB  - Androgen production by adult rat Leydig cells is stimulated by pituitary LH but
      can also be modulated in vitro by paracrine stimulatory and inhibitory factors,
      many of which belong to growth factor families. Their actions are mediated
      through cell surface or extracellular matrix proteoglycans and the aim of this
      study was to determine the role of cell surface heparan sulfate proteoglycans in
      the regulation of testosterone secretion by adult rat Leydig cells. The presence
      of sodium chlorate (25 mM) and protamine sulfate (10 micrograms/ml) inhibited
      testosterone production by LH stimulated cells by over 50%, but had no effect on
      unstimulated cells. The LH responsiveness and testosterone production returned to
      normal after these agents were removed from the culture media. No significant
      difference in LH receptor numbers at the end of the culture period was seen
      between sodium chlorate treated and untreated cells. Testosterone production by
      dibutryl-cAMP stimulated Leydig cells was also inhibited by sodium chlorate. The
      addition of heparin inhibited testosterone production by LH stimulated cells in a
      dose-dependent manner, however, in unstimulated Leydig cells heparin stimulated
      testosterone production to up to 50% of that seen in LH stimulated cells. These
      data suggest that cell surface heparan sulfate proteoglycans modulate
      testosterone production by adult Leydig cells in vitro, and that this may involve
      the autocrine actions of heparin binding growth factors on the Leydig cells.

PMID- 8735592
TI  - Androgen regulation of the messenger RNA encoding diazepam-binding inhibitor/acyl
      CoA-binding protein in the rat.
AB  - Our recent finding that diazepam-binding inhibitor/acyl-CoA-binding protein
      (DBI/ACBP) expression is regulated by androgens in the human prostatic
      adenocarcinoma cell line LNCaP, prompted us to study whether androgen regulation
      of DBI/ACBP also occurs in vivo in the prostate and in other organs of the rat.
      Northern blot analysis demonstrated that DBI/ACBP transcripts were expressed in
      male accessory sex organs such as ventral prostate, dorsolateral prostate,
      seminal vesicles and coagulating glands. Castration caused a 1.7- to 2.7-fold
      reduction in the levels of DBI/ACBP transcripts over a period of 6 days.
      Readministration of androgens during the last 3 days led to 4.2- to 7.5- fold
      higher levels of DBI/ACBP transcripts than in untreated castrates. In situ
      hybridization revealed that in the ventral prostate, DBI/ACBP transcripts were
      expressed predominantly in epithelial cells and that the observed effects of
      androgens were due both to modulation of gene expression per cell and to changes
      in cell composition. Androgen regulation of DBI/ACBP mRNA expression was also
      observed in the lacrimal glands, the adrenals, and the submandibular glands, but
      not in the liver and the kidney. These findings demonstrate that DBI/ACBP is
      androgen-regulated in vivo in various organs of the rat. In view of the proposed
      role of DBI/ACBP in the control of multiple biological processes, DBI/ACBP may be
      one of the target genes by which androgens affect a variety of physiological
      processes.

PMID- 8735593
TI  - Nitric oxide donors decrease the function and survival of human pancreatic
      islets.
AB  - Nitric oxide (NO) has been proposed as a possible mediator of beta-cell damage in
      human IDDM. This hypothesis is based on in vitro studies with rodent pancreatic
      islets. In the present study we examined whether human beta-cells are affected by
      NO. In view of species differences in beta-cell sensitivity to damaging agents,
      rat islets were investigated in parallel. Isolated islets were exposed for 90 min
      to different concentrations of three chemically unrelated NO donors, SIN-1, GSNO
      or RBS. At the end of this incubation, human insulin release was mostly similar
      in control and NO-treated islets but, 48 h later, islet retrieval, islet DNA and
      insulin content, and glucose-induced insulin release were markedly lower in
      islets exposed to NO donors. Rat islets were already inhibited during the initial
      90 min; 48 h later their loss in beta-cell function was similar to that in human
      islets. Nicotinamide or succinic acid monomethyl ester partially protected
      against SIN-1 induced islet cell loss, but not against the functional inhibition
      of human pancreatic islets. Exposure of human or rat islets to RBS was associated
      with significant DNA strand breakage, as judged by the comet assay (single cell
      gel electrophoresis) and by ultrastructural signs of cell damage. DNA damage was
      more severe in rat islet cells exposed to similar amounts of RBS. It is concluded
      that NO donors can damage human pancreatic islets, an effect paralleled by
      induction of nuclear DNA strand breaks.

PMID- 8735594
TI  - Expression of human relaxin genes: characterization of a novel alternatively
      spliced human relaxin mRNA species.
AB  - Relaxin is a two-chain peptide hormone encoded by two non-allelic genes in humans
      and great apes, and by a single gene in all other species studied. We have
      characterized the expression of the human relaxin genes (H1 and H2) in placenta,
      decidua, prostate and ovary by reverse-transcription/polymerase chain reaction
      (RT/PCR). H2 relaxin mRNA was detected in the ovary, term placenta, decidua, and
      prostate gland. In contrast, H1 gene expression was detected only in the prostate
      gland. In addition to the relaxin PCR product of the predicted size (486 bp), a
      larger relaxin-specific product (587 bp) was detected in both H1 and H2
      amplifications and in amplifications of chimpanzee relaxin from placenta and
      corpus luteum. Sequencing of human and chimpanzee PCR products, and human relaxin
      genomic clones, revealed that the larger product arises from an alternatively
      spliced relaxin mRNA species incorporating an extra exon. This is the first
      evidence that the structure of the human and chimpanzee relaxin genes differ from
      that of other characterized relaxin genes, such as pig and rat. The novel peptide
      arising from this alternate message would be identical to prorelaxin in the B
      chain and part of the C-peptide (extending to the position of the intron) but
      would differ from prorelaxin in the carboxy-terminal domain. Observation of a
      similar mRNA species in the chimpanzee suggests that this conserved relaxin-like
      peptide may have a significant biological role.

PMID- 8735595
TI  - Growth hormone stimulates androsterone synthesis by rat theca-interstitial cells.
AB  - The aim of this study was to assess the possible role of growth hormone (GH) on
      androsterone synthesis. This effect was analyzed in theca-interstitial cells
      obtained from immature female rats. The addition of GH to the cultures
      significantly stimulated androsterone (A) synthesis in a dose- and time-dependent
      way and this effect was not due to a cellular number increase. When added to the
      hCG cultures, GH significantly enhanced androgen production even though it did
      not synergyze with the chorionic gonadotropin. The addition of antibodies anti
      IGF-I to the GH cultures did not modify the growth hormone effect suggesting that
      GH probably does not require IGF-I to achieve its effect on A production.
      Finally, no effect of GH on cAMP levels were observed in the cultures at the end
      of the treatment. Our results demonstrate that GH is able to significantly induce
      A synthesis by rat theca-interstitial cells. Since the presence of GH and its
      receptors in the ovary is now well established the present data strongly suggest
      a potential relevance of GH in reproductive biology.

PMID- 8735596
TI  - Selective translocation of non-conventional protein kinase C isoenzymes by
      gonadotropin-releasing hormone (GnRH) in the gonadotrope-derived alpha T3-1 cell
      line.
AB  - Gonadotropin-releasing hormone acts via G-protein coupled receptors to stimulate
      polyphosphoinositide-specific phospholipase C (PIC) with consequent elevation of
      cytosolic Ca2+ and activation of protein kinase C (PKC). Whereas Ca2+ is known to
      mediate stimulation of exocytotic gonadotropin release by GnRH, the identity of
      the PKC isoenzymes activated by GnRH and their physiological role in gonadotropes
      are poorly understood. In many systems translocation of PKC (from cytosolic to
      particulate fractions of cellular homogenates) has been taken as evidence of
      hormonal activation of PKC and down regulation of PKC (by prolonged treatment
      with PKC-activating phorbol esters) has been used extensively to investigate the
      role of PKC in hormone action. Here we have assessed the influence of GnRH and
      phorbol esters on translocation and down regulation of PKC isoenzymes identified
      by Western blotting with isoenzyme-specific antibodies in alpha T3-1 cells (a
      gonadotrope-derived cell line). These cells were found to posses PKCs alpha,
      epsilon and zeta but not beta, delta (present in rat pituitaries) or gamma
      (present in rat brains). In short-term stimulations (10 min), the PKC-activating
      phorbol esters, PMA and PDBu, caused concentration-dependent increases in the
      proportion of PKC alpha and PKC epsilon recovered from the particulate fraction
      of alpha T3-1 cells, but did not induce measurable translocation of PKC zeta. The
      inactive phorbol ester 4 alpha PDBu did not cause translocation of any of these
      isoenzymes. GnRH treatment induced a concentration-dependent increase in the
      proportion of particulate PKC epsilon and PKC zeta but had no measurable effect
      on PKC alpha translocation. In longer incubations (6-48 h) GnRH failed to cause
      measurable down-regulation of these isoenzymes whereas PMA treatment led to a
      clear down regulation of PKCs alpha and epsilon (albeit with different kinetics).
      The data demonstrate the differential activation and down regulation of PKC
      isoenzymes by GnRH versus PMA, which are clearly pertinent to the design of
      experiments intended to address the role of such isoenzymes in GnRH action.
      Moreover, they provide the first demonstration of hormonal regulation of an
      atypical PKC isoenzyme (PKC zeta) in pituitary cells.

PMID- 8735597
TI  - Expression of the rat BFGF antisense RNA transcript is tissue-specific and
      developmentally regulated.
AB  - The basic fibroblast growth factor (bFGF) gene locus is transcribed into a number
      of mRNA transcripts including an antisense mRNA derived from the opposite DNA
      strand of the bFGF gene. Expression of this natural antisense RNA has been
      implicated in regulation of the bFGF sense mRNA expression and turnover. In the
      present study we examined the developmental pattern of expression of the bFGF
      antisense transcript in fetal and postnatal rat tissues. Northern hybridization
      with a strand-specific cRNA probe detected a 1.5-kb polyadenylated antisense RNA
      in all tissues examined except brain, in which two transcripts were detected as a
      doublet of approximately 1.3-1.5 kb in size. The level of antisense transcript
      expression was markedly tissue- and age-dependent. In the developing brain, both
      sense and antisense transcripts were detected by Northern hybridization, but the
      pattern of their expression was inversely related. The 6.0-kb bFGF sense
      transcript increased in an age-dependent manner from days 3-30 of postnatal
      development while the antisense transcript decreased to nearly undetectable
      levels over the same period. In embryonic (days 15-19) liver, kidney, heart and
      intestine bFGF antisense RNA expression was low but increased dramatically at
      parturition, rising 5-10-fold over fetal levels by 10 days of age, then declined
      slowly to a new steady-state level in adult tissues. The level of antisense RNA
      in these tissues was much higher than that of bFGF sense mRNA, which was
      undetectable by Northern analysis. Sense and antisense trancripts were also
      detected in midgestational (11.5 days) embryos by RT-PCR. Antisense expression
      did not increase when embryos were explanted and cultured for 48 h (9.5-11.5
      days). The apparent reciprocal relationship between the abundance of sense and
      antisense bFGF transcripts in developing brain supports the possibility of a
      regulatory role for the antisense transcript in this tissue. There was no
      evidence for a reciprocal relationship between sense and antisense expression in
      the other tissues examined, indicating that the relationship between sense and
      antisense RNA expression may be tissue-specific.

PMID- 8735598
TI  - EGF increases retinoid X receptor-alpha expression in human trophoblastic cells
      in culture: relationship with retinoic acid induced human chorionic gonadotropin
      secretion.
AB  - In the present study, the effect of retinoic acid (RA) and epidermal growth
      factor (EGF) on the functions of human trophoblastic cells in culture were
      analysed. In these cells, RA potentiated the hCG secretion increase induced by
      EGF. To gain a better understanding of such a synergistic effect, the expression
      of retinoic acid receptors (RAR alpha and beta) and retinoid X receptor (RXR
      alpha) was studied by immunoblotting in RA- and EGF-treated cells. EGF treatment
      specifically increased the level of RXR alpha protein and RXR alpha transcripts.
      In parallel, we demonstrated that the choriocarcinoma cells JEG 3, which respond
      to RA by an increase in hCG secretion, express constitutively high levels of RXR
      alpha protein. Furthermore, RXR alpha-transfected trophoblastic cells also become
      RA responsive for hCG secretion. All these data suggest that RXR alpha expression
      is modulated by EGF, and may be involved in the effect of RA on hCG secretion.

PMID- 8735599
TI  - The H295R human adrenocortical cell line contains functional atrial natriuretic
      peptide receptors that inhibit aldosterone biosynthesis.
AB  - The inhibitory effect of atrial natriuretic peptide (ANP) on angiotensin II (AII)
      stimulated aldosterone secretion has been previously studied in rat and bovine
      adrenal zona glomerulosa cells in primary culture. However the understanding of
      the mode of action of ANP at the molecular level has been hampered by limitations
      of those primary cell culture systems and by the lack of cell lines from human
      adrenal cortex. Here we demonstrate the presence of fully functional ANP
      receptors in the recently characterized AII-responsive adrenocortical carcinoma
      cell line H295R. Specific saturable binding of 125I-rANP to H295R cell membrane
      preparations revealed a single class of high affinity binding sites with a
      density of 20 fmol/mg of protein. The pharmacological profile of this ANP
      receptor was documented by competitive binding of 125I-rANP with naturally
      occurring natriuretic peptides. rANP was the most potent with a Kd of 42 pM.
      pBNP32 was less potent with a Kd of 174 pM. 125I-rANP binding was not competed by
      pCNP (NPRB-specific ligand) nor by C-ANF (NPRC-specific ligand). Photoaffinity
      labeling of membrane preparations with 125I-BPA-ANP revealed a single specific
      protein of molecular weight around 130 kDa. This protein was further identified
      by immunodetection with a specific antibody directed to the human ANP-specific
      receptor NPRA. Natriuretic peptides stimulated cGMP production by the receptor
      coupled guanylate cyclase with the same specificity. Aldosterone production by
      AII-stimulated H295R cells was dose-dependently inhibited by rANP with an ED50 of
      1.5 nM. In addition, we used this model to test two chimeric analogs of ANP and
      BNP. pBNP1 and pBNP3 were, respectively, 4- and 2-fold more potent than rANP in
      competing for 125I-rANP binding with Kd of 10 and 20 pM. pBNP1 was 24-fold more
      potent in inhibiting AII-stimulated aldosterone production with ED50 of 63 pM.
      pBNP1 is therefore the most potent natriuretic peptide analog tested. In summary,
      the human H295R cell line contains NPRA receptors positively coupled to the
      particulate guanylate cyclase and that antagonize angiotensin II stimulation of
      aldosterone secretion.

PMID- 8735600
TI  - Fourier analysis of differential light scattering for the quantitation of FSH
      response associated with structural changes in immortalized granulosa cells.
AB  - We have established granulosa cell lines which express constitutively the rat FSH
      receptors by cotransfection of primary granulosa cells obtained from preovulatory
      follicles with SV40 DNA, Ha-ras oncogene and a plasmid expressing FSH receptors.
      These cells respond specifically to ovine and human FSH by cell rounding,
      intracellular cAMP accumulation, and progesterone secretion in a dose-dependent
      manner. A new method for the demonstration and quantitation of changes in cell
      shape-Small Angle Laser Light Scattering (SALLS) analysis-has been utilized for
      measurement of cell rounding in response to FSH stimulation in these cells. When
      cells were incubated with increasing doses of either ovine or human FSH, partial
      rounding of cells was observed at FSH concentrations as low as 24 pM, while
      complete rounding of cells was observed at a range of 0.24-2.4 nM of FSH.
      Following aldehyde fixation, hormone-treated cells were examined using the method
      of SALLS analysis. Histograms obtained by applying SALLS analysis on FSH
      stimulated GFSHR-17 cells were a reflection of the structural changes induced by
      the hormone. FSH- and forskolin-incubated cells yielded structured distributions
      with defined mean size and standard deviations. Moreover, the increase in
      sharpness of dominant peak in the histogram was correlated with elevated
      concentration of FSH in a dose dependent manner. In conclusion, cellular response
      to FSH is correlated with a specific pattern of light scattered in immortalized
      granulosa cells expressing functional FSH receptors. Therefore, SALLS analysis
      may serve as a useful tool for in vitro bioassay of the gonadotropic hormone.
      Moreover, this method may lend itself to in vitro bioassay of any hormone that
      induces specific morphological changes in target cells.

PMID- 8735601
TI  - Nuclease sensitivity of the human growth hormone-chorionic somatomammotropin
      locus in pituitary and placenta suggest different mechanisms for tissue-specific
      regulation.
AB  - The five human growth hormone (GH) and chorionic somatomammotropin (CS) genes are
      located at a single locus on chromosome 17. These genes share extensive
      nucleotide sequence similarity (approximately 94%) even in their flanking DNA,
      yet GH-N is expressed efficiently in the pituitary under the control of the
      pituitary-specific factor GHF-1/Pit-1 and the remaining CS-A, CS-B, CS-L and GH-V
      genes are transcriptionally active in the placenta. Despite this specificity in
      vivo, a truncated CS-A promoter can bind GHF-1/Pit-1 and allow CS-A promoter
      activity in pituitary cells in vitro. With a view to assessing whether the
      placental genes of the GH/CS locus possess a different chromatin structure in the
      pituitary and are, thus, less transcriptionally active than the GH-N gene, we
      have compared the DNAase I sensitivity of GH/CS in isolated pituitary and
      placenta cell nuclei. Our data indicate that these genes are equally sensitive in
      isolated human pituitary nuclei. By contrast, the CS-A, CS-B and CS-L genes were
      significantly (P < 0.05) more sensitive than the GH-N gene in isolated human
      placenta nuclei. Although just not significant, the GH-V gene was slightly more
      sensitive than the GH-N gene. This pattern was also seen with nuclei from human
      choriocarcinoma BeWo and JEG-3 cells, which express low and extremely low levels
      of CS RNA, respectively, but was distinct from the pattern observed in the non
      placental human cervical carcinoma HeLa cell line. These data indicate that the
      inactivity of the CS genes in the pituitary does not correlate with a 'closed'
      chromatin structure. However, they are consistent with a role for a more 'open'
      chromatin conformation in placenta-specific expression, but not necessarily high
      levels of transcriptional activity.

PMID- 8735602
TI  - Pancreatic islet B-cell individual variability rather than subpopulation
      heterogeneity.
AB  - Isolated rat pancreatic islet B-cells loaded with the Ca2(+)-sensitive
      fluorochrome Fluo-3 were examined by single-step flow cytometry at increasing
      concentrations of D-glucose (1.0 to 20.0 mM). The near forward scatter of light
      was unaffected by changes in hexose concentration. The Fluo-3 fluorescent signal
      slightly decreased when the glucose concentration was raised from 1.0 to 5.0 mM,
      and progressively increased at higher hexose concentrations. The fluorescence
      attributable to endogenous NAD(P)H increased dramatically throughout the full
      range of D-glucose concentration, with a typical sigmoidal concentration-response
      relationship. No evidence for a bimodal frequency distribution of these variables
      was found, whether at low or high D-glucose concentrations. The dispersion of
      individual NAD(P)H measurements, as judged by either their coefficient of
      variation or the height of their modal peak, was less pronounced at high than at
      low D-glucose concentrations. These findings document vastly different
      concentration-response relationships for metabolic and ionic variables in glucose
      stimulated B-cells. They confirm that all B-cells do not display an identical
      behavior, but argue against the existence of subpopulation heterogeneity in their
      responsiveness to D-glucose.

PMID- 8735603
TI  - Expression of estrogen receptor variants in normal and neoplastic human uterus.
AB  - Estrogen receptor variants lacking internal exons and representing dominant
      positive and negative activity may be involved in the initiation and/or
      progression of endocrine dependent tumors. To assess the role of estrogen
      receptor in uterine disease, we have analyzed both normal and neoplastic uterine
      samples for the presence of variant estrogen receptors using the sensitive
      technique of RT-PCR and direct automated DNA sequencing of the amplified
      products. Our analysis was conducted to determine the presence of spliced
      variants lacking exons 3 through exon 8. We demonstrate that both the normal and
      neoplastic human uterus contains a number of spliced variants of the estrogen
      receptor that co-exist with the wild type receptor. Variants lacking exons 4, 5
      and 7 but not exons 3 and 6 were detected. Also, a novel partial deletion in exon
      8 was detected in both the normal and neoplastic tissues, although a total
      deletion of this exon was not observed. In addition another region of exon 8
      deletion was found to be present in one tumor tissue which also contained an
      insertion within this region, however, other tumors did not contain this variant.
      In addition, double exon deletion variants were observed lacking exons 3 and 4,
      exons 4 and 5, and exon 7 with part of exon 8. Although our data represents a
      limited number of samples it suggests that splicing of the estrogen receptor
      message occurs in the normal physiological setting. There does not appear to be
      any association between the presence or absence of spliced variants of estrogen
      receptor and uterine tumor formation at the mRNA level.

PMID- 8735604
TI  - Heterogeneity of growth hormone (GH)-producing cells in aging male rats:
      ultrastructure and GH gene expression in somatotrope subpopulations.
AB  - Mammalian aging is characterized by a decline in the content and release of
      pituitary growth hormone (GH). However, few studies on the age-related changes in
      the population of GH-producing cells (somatotropes) have been carried out. We
      have investigated whether changes in number, ultrastructure and GH gene
      expression in subpopulations of somatotropes could explain the reduced GH release
      in aged rats. Three representative ages were studied: adult (5-month-old), old
      (19-month-old), and senescent (26-month-old) male rats. The total number of
      immunoreactive-GH cells per pituitary gland remained invariable to age. The
      separation of dispersed pituitary cells on a density gradient yielded two
      somatotrope subpopulations, of low density (LD) and high density (HD). Both
      subpopulations were equally represented in adults, whereas in old and senescent
      rats a predominance of LD-somatotropes was observed. Morphometric analysis showed
      that subpopulations exhibited storage and biosynthetic features inversely
      related. In LD-somatotropes, rough endoplasmic reticulum (RER) was more prominent
      but secretory granules (SG) were less abundant than in HD somatotropes.
      Concurrently, in situ hybridization for GH mRNA showed that GH gene expression
      was higher in LD-cells. Differences between subpopulations were essentially
      retained through the animals' lifespan, but small-sized SG, reduced RER, and low
      GH mRNA levels were inherent to aging both in LD- and in HD-somatotropes. The
      present findings demonstrate that the reduced content of pituitary GH in aged
      male rats is not due to a diminished number of GH-producing cells, but to the
      numerical predominance of scarcely granulated LD-somatotropes, combined with the
      decline in GH biosynthetic capacity observed in both subpopulations. In addition,
      age-related changes in ultrastructure and GH gene expression suggest a chronic
      inhibition of GH release and/or a weak stimulation of GH biosynthesis affecting
      both subpopulations.

PMID- 8735605
TI  - Different sites of action of arachidonic acid on steroidogenesis in rat Leydig
      cells.
AB  - The present study in purified rat Leydig cells shows that arachidonic acid may
      act as an intratesticular factor regulating LH-mediated testicular
      steroidogenesis. Arachidonic acid decreased, in a dose-dependent manner, the LH
      stimulated cAMP and testosterone levels, over 2 h incubation. Incubation of
      Leydig cells with arachidonic acid did not modify 125I-hCG binding to the cells
      as compared to control, showing that the action of arachidonic acid is not
      related to a decrease of hCG binding to the cells. Forskolin-stimulated cAMP and
      testosterone production were inhibited by 51.65 and 70.9%, respectively, in the
      presence of arachidonic acid (100 microM), although the ED50 for the diterpene
      was not changed. When isobutyl-methyl-xanthine was added to the incubation
      medium, the same percentage of inhibition was found indicating that arachidonic
      acid inhibition of cAMP production is not due to stimulation of Leydig cell
      phosphodiesterase activity. Pretreatment of the cells with pertussis toxin, to
      inactivate Gi, was also without effect on arachidonic acid inhibition of LH
      stimulated cAMP production, but pertussis toxin abolished the inhibitory effects
      of arachidonic acid when adenylate cyclase was stimulated with forskolin.
      However, arachidonic acid addition resulted in inhibition of LH- and forskolin
      stimulated testosterone production, even if the cells were pretreated with
      pertussis toxin. It can be concluded that: (1) The inhibitory effect of
      arachidonic acid is neither due to a decrease of hCG binding to Leydig cells nor
      to a stimulation of cell phosphodiesterase activity; (2) arachidonic acid
      modulates cAMP production at two different levels, either by activation of Gi
      protein and by inhibition of Gs protein or adenylate cyclase; (3) the effect of
      arachidonic acid on steroidogenesis is also beyond cAMP formation.

PMID- 8735606
TI  - Inhibition of IGF II-induced redistribution of mannose 6-phosphate receptors by
      the phosphatidylinositol 3-kinase inhibitor, wortmannin.
AB  - The effects of wortmannin, a selective inhibitor of phosphatidylinositol (PI)3
      kinase on insulin-like growth factor II (IGF II)-induced redistribution of the
      300 kDa mannose 6-phosphate/IGF II receptor (MPR 300) has been studied in human
      hepatoma HepG2 cells. IGF II increased the expression of MPR 300 at the cell
      surface threefold that was completely abolished by wortmannin at 100-300 nM.
      Higher concentrations of wortmannin also reduced the basal MPR 300-dependent
      uptake of ligands to 68% of controls. Neither the transport of two lysosomal
      enzymes nor the secretion of the IGF binding protein-1 were affected by
      wortmannin. These results show that activation of PI3-kinase plays a critical
      role in the IGF II-stimulated redistribution of MPR 300 initiated rather by IGF
      II binding to tyrosine kinase receptors than to the MPR 300.

PMID- 8735607
TI  - Estrogen-induced changes in rRNA accumulation and RNA polymerase I activity in
      the rat pituitary: correlation with pituitary tumor susceptibility.
AB  - Chronic treatment with the synthetic estrogen diethylstilbestrol induces
      pituitary tumors in rats and the susceptibility to such tumors is highly strain
      dependent. The Fischer 344 (F344) strain, which is particularly susceptible,
      develops pituitary tumors after 30-55 days of estrogen treatment. In contrast,
      the Sprague-Dawley (SD) strain is relatively resistant to such tumors. DES
      implants (5 mg) were placed in 21-day-old male rats over a 10-day period and
      changes in their testes and pituitaries were monitored. Both F344 and SD strains
      responded similarly by exhibiting a measurable decrease in testes weight to one
      third that of controls on day 10. In F344 rats, DNA synthesis in the pituitary
      increased to 228% as compared with controls after 3 days of DES treatment and
      remained high on days 7 and 10. In SD rats, DNA synthesis increased to only 150%
      of that exhibited by controls on day 3 and started to decline on day 7.
      Surprisingly, total RNA accumulation also responded to DES differentially between
      these two strains. In F344 rats, the RNA level was 250% as compared with that of
      controls after 3 days of DES treatment and continued to increase gradually on
      days 7 and 10. The RNA level in the SD strain increased only slightly from the
      same DES treatment. A nuclear run-on assay showed elevated pituitary
      transcription of ribosomal DNA in the F344 rats after 3 days of estrogen
      administration. The enzymatic activity of pituitary RNA polymerase I, the enzyme
      responsible for initiating rRNA synthesis, increased twofold in F344 rats when
      measured after 3 days of estrogen treatment whereas no increase was observed in
      the SD rats. These results suggest that estrogen-induced changes in the
      accumulation of rRNA occur at a very early stage in tumorigenesis, prior to any
      visible tumor growth in the rat pituitary.

PMID- 8735609
TI  - Distinctiveness and very short-term serial position effects.
AB  - The serial position function reflects better memory for the first and last few
      items in a list than for the middle items. Four experiments examined the effects
      of temporal spacing on the serial position function for five-item lists that took
      between 0.5 seconds and 1.1 seconds to present. As with recall of far longer
      lasting lists, recency and other robust serial position effects were observed
      with both free and serial recall. We demonstrate that temporal schedules of
      presentation control recall probability in predictable ways, and conclude that
      very fleeting lists obey similar principles as do longer-lasting lists. We
      compare both sets of findings with predictions from the dimensional
      distinctiveness framework.

PMID- 8735608
TI  - Expression of transcripts of interleukin-6 and related cytokines by human breast
      tumors, breast cancer cells, and adipose stromal cells.
AB  - The expression of transcripts of cytokines of the interleukin-6 (IL-6) family has
      been examined in human breast tumors, breast cancer cell lines, and adipose
      stromal cells, by means of reverse transcription polymerase chain reaction
      amplification. Of the six breast tumor samples examined, all expressed
      transcripts encoding IL-6 and Leukemia Inhibitory Factor (LIF). Four of the
      samples also expressed transcripts for oncostatin M (OSM) and IL-11, and three
      expressed the IL-6 receptor. Adipose stromal cells expressed IL-6, IL-11 and LIF,
      but not the IL-6 receptor, consistent with previous conclusions that IL-6
      activity in these cells required addition of IL-6 soluble receptor. In the case
      of T47D cells, expression of IL-11 protein was confirmed by immunotitration.
      Moreover, in these cells, expression of IL-11 transcripts was induced 3-fold by
      addition of estradiol to the culture medium. These results add credence to our
      previous proposal that breast cancer development is regulated in part by local
      autocrine and paracrine mechanisms via epithelial/mesenchymal interactions, in
      which estrogen produced by stromal cells surrounding the tumor acts to stimulate
      the production of growth factors and cytokines by the tumor cells. Some of these
      may act to stimulate further the growth and development of the tumor, while these
      or other factors may act on the surrounding mesenchymal cells in a paracrine
      fashion to stimulate aromatase expression in the presence of glucocorticoids.
      Thus, a positive feedback loop is established which leads to the development and
      growth of the tumor.

PMID- 8735610
TI  - A developmental evaluation of frequency memory for actions presented in lists,
      scripts, and stories.
AB  - In Experiment 1, adults estimated the frequency of typical and atypical actions
      presented in stories about scripted routines. Judgments of frequency were more
      accurate for atypical than for typical actions. In Experiments 2 and 3, children
      and adults estimated the frequency of atypical actions that were presented in
      lists, or embedded in stories that described activities that are scripted, or in
      stories that described unfamiliar activities. The results supported Hasher and
      Zacks's (1984) proposal that encoding of frequency information is automatic and
      invariant across a wide range of ages. However, both children's and adults'
      frequency estimates were influenced by manipulations that varied the difficulty
      of retrieving the representation of each occurrence of an event. The studies also
      provide novel support for the Script-Pointer-Plus-Tag theory of script memory.

PMID- 8735611
TI  - Rehearsal strategies, test expectancy, and memory monitoring in free recall.
AB  - Three experiments were carried out to determine (a) the effectiveness of
      associative rehearsal and rote repetition for long-term recall with and without
      expectation of a later recall test, and (b) the subjects' ability to assess their
      own future recall performance. The overall results showed that a test expectancy
      effect was not obtained when a voluntary selection in strategies was prohibited,
      but was found for subjects not instructed in the use of any particular strategy.
      It is also shown that the subjects could predict correctly that the items studied
      with associative rehearsal would be recalled more successfully at the final test
      than when they were studied with rote repetition. A superiority of associative
      rehearsal for prediction was not found when the subjects used only one type of
      rehearsal, but was found when they were not given the immediate test. The results
      suggest that the expectancy effect can be explained in terms of subjects'
      intentional shifts of strategies based on their metacognitive assessment of such
      strategies.

PMID- 8735612
TI  - Phonological working memory and reading in test anxiety.
AB  - Texts were presented sentence by sentence (Experiment 1) or word by word
      (Experiment 2) at a fixed rate to subjects high or low in test anxiety, under
      various conditions: no interference, concurrent articulatory suppression, and
      concurrent irrelevant speech (presented auditorily). High-anxiety subjects
      produced overt articulation more frequently than low-anxiety subjects, especially
      in the irrelevant speech condition. The most salient finding was an interaction
      between anxiety and interference on comprehension performance: under word-by-word
      but not under sentence-by-sentence-presentation, anxious subjects showed poorer
      comprehension than non-anxious subjects in both conditions known to interfere
      with the articulatory loop (i.e. articulatory suppression, and irrelevant
      speech), but equivalent comprehension in the no interference condition. These
      findings suggest (a) that the articulatory loop has a special compensatory role
      for anxious individuals in reading comprehension, and (b) that the importance of
      this auxiliary mechanism is enhanced when other strategies, such as regressive
      fixations and control of reading speed, cannot be used.

PMID- 8735613
TI  - Reinstatement of prior processing and repetition priming.
AB  - Two principal accounts of repetition priming describe either reinstatement of
      prior processing demands or activation of item-specific representations used in
      stimulus recognition as mechanisms by which the effect occurs. The former type of
      account predicts maximal priming when the same task is performed at first and
      second encounter (i.e. at training and test). The latter type of account predicts
      priming in any test task that requires access to item-specific representations as
      long as those items have been recognised earlier, regardless of the training
      task. An experiment was performed to test these contrasting predictions, in which
      subjects matched pairs of object pictures on the basis of either the colour of a
      segment of each object or on the basis of each object's identity. No repetition
      priming was observed when subjects performed colour matching at both first and
      second encounter. Priming was observed when responses were made on the basis of
      identity at both first and second encounter, and there was equivalent priming
      when colour matching was performed at the first encounter and identity matching
      at the second encounter. These results pose problems for theories of repetition
      priming based on reinstatement of prior processing demands, as colour matching
      did not prime subsequent colour matching (exact reinstatement of processing
      demands), whereas it did prime subsequent identity matching as much as did prior
      identity matching (a change in processing demands). These results are consistent
      with repetition priming occurring within a system that represents the identities
      of items.

PMID- 8735614
TI  - Reporting the dates of events: the role of prior knowledge.
AB  - In seeking to understand the processes involved when people report temporal
      information from memory, two general domains have been studied: date generation
      and duration estimation. Both domains are combined in the present study, which
      establishes, first, that people have similar expectations as to the usual lengths
      of the temporal intervals between events, and second, that expectations about
      intervals affect reconstructions of event dates. Similar expectations for
      intervals of certain vignettes (e.g. leaving on and returning from a honeymoon)
      were uncovered in Experiment 1. In Experiment 2, subjects read the same
      vignettes, but the dates used created temporal intervals that were less than,
      greater than, or equal to, the usual temporal intervals from Experiment 1.
      Subjects then recalled either one or both of the dates they had read. Results
      indicated that reported dates were influenced by both the dates presented and
      expectations based on prior knowledge.

PMID- 8735615
TI  - The effect of nociceptin on Ca2+ channel current and intracellular Ca2+ in the SH
      SY5Y human neuroblastoma cell line.
AB  - The human neuroblastoma cell line SH-SY5Y expresses the 'orphan' opioid receptor
      (ORL1). We have demonstrated that nociceptin, the putative endogenous ligand for
      ORL1, produces a concentration-dependent inhibition of the N-type calcium channel
      current in these cells (IC50 42 nM). In addition, in the presence of carbachol,
      nociceptin increased the intracellular concentration of Ca2+ (EC50 60 nM). Both
      effects of nociceptin were blocked by pertussis toxin pretreatment but not by the
      opioid antagonists CTAP (1 microM), naltrindole (1 microM) and naloxone (10
      microM).

PMID- 8735616
TI  - An interaction of ondansetron and dexamethasone antagonizing cisplatin-induced
      acute and delayed emesis in the ferret.
AB  - 1. Cisplatin, 5 mg kg-1, i.p., administered as a single treatment, induced an
      acute (day 1) and delayed (days 2 and 3) emetic response in the ferret that was
      used to investigate the potential anti-emetic activity of ondansetron and
      dexamethasone and their interaction over a three day period. 2. Ondansetron, 1 mg
      kg-1, i.p., administered three times per day in two experiments, antagonized
      significantly the retching and vomiting that occurred on days 1 and 2 by 60-76
      and 73-84%. On the third day of treatment there was a trend for a 38% reduction
      in one experiment and a 74% reduction in the other. 3. There was a trend for
      dexamethasone, 1 mg kg-1, i.p., administered as a single daily injection for
      three days, to reduce by 37% the retching and vomiting response that occurred on
      day 1, the reduction of 77% on day 2 achieved significance and dexamethasone non
      significantly increased the retching and vomiting response by 46% on day 3.
      However, dexamethasone 1 mg kg-1 i.p. administered three times per day for three
      days significantly reduced the retching + vomiting response by 85, 97 and 86% on
      days 1, 2 and 3 respectively. 4. The combination of dexamethasone, 1 mg kg-1,
      i.p., as single daily injections with ondansetron, 1 mg kg-1, i.p., administered
      three times per day improved the control of the retching and vomiting response,
      significantly reducing the total numbers of retches and vomits by more than 70%
      over a three day period. The combination of dexamethasone (1.0 mg kg-1) and
      ondansetron (1.0 mg kg-1), both administered three times daily, abolished
      cisplatin-induced emesis over the three day period. 5. The three times per day
      administration of ondansetron, 1 mg kg-1, i.p., plus dexamethasone, 1 mg kg-1,
      i.p., administered only on day 1 prevented day 1 emesis but did not modify the
      retching and vomiting that occurred on days 2 and 3. 6. The present results
      indicate that ondansetron and dexamethasone significantly reduce cisplatin
      induced emesis in the ferret during both the acute and delayed phase; drug/co
      treatment can exert an additive action to abolish cisplatin-induced emesis. The
      ferret model may be useful to detect anti-emetic drug action for treatment of
      chemotherapy-induced acute and delayed emesis in man.

PMID- 8735617
TI  - Effect of lacidipine on fatty and proliferative lesions induced in
      hypercholesterolaemic rabbits.
AB  - 1. The in vivo antiatherogenic activity of the calcium antagonist, lacidipine,
      was investigated in two different types of atherosclerotic lesions (proliferative
      and fatty lesions) induced in rabbits. 2. The proliferative lesion was obtained
      by positioning a hollow silastic collar around one carotid artery, while aortic
      fatty lesions were induced by cholesterol feeding. Cholesterol (1%) and
      lacidipine (1, 3, and 10 mg kg-1) were given daily mixed with standard diet for 8
      weeks to White New Zealand rabbits. The intimal hyperplasia (proliferative
      lesion) was induced 6 weeks after dietary and drug treatment started. 3. The
      neointimal formation was determined by measuring cross sectional thickness of
      intimal (I) and medial (M) tissue of fixed arteries. In untreated animals (n =
      5), 14 days after collar positioning an intimal hyperplasia was clearly
      detectable: the arteries with no collar (sham) showed an I/M tissue ratio of 0.03
      +/- 0.02, whereas in the carotid with collar the ratio was 0.62 +/- 0.12. In
      lacidipine-treated animals a significant and dose-dependent effect on
      proliferative lesions at all three doses tested, was observed. I/M ratios were
      0.47 +/- 0.02, 0.40 +/- 0.09, 0.32 +/- 0.02 for doses 1, 3, and 10 mg kg-1 day-1,
      respectively (P < 0.05). 4. The fatty lesion extent was significantly reduced by
      lacidipine at the 10 mg kg-1 day-1 dose, although a trend was also observed with
      lower dosage. 5. These results suggest a direct antiatherosclerotic effect of
      lacidipine, independent of modulation of risk factors such as
      hypercholesterolaemia and/or hypertension. Furthermore, the proliferative lesions
      are apparently more sensitive to lacidipine than are lipid-rich lesions.

PMID- 8735618
TI  - Paracrine renal endothelin system in rats with liver cirrhosis.
AB  - 1. Liver cirrhosis was induced in rats by CCl4 administration. We analysed the
      expression of endothelin receptor subtypes in the renal cortex and medulla using
      Scatchard analysis and receptor autoradiography, and measured plasma as well as
      renal-tissue endothelin-1 concentrations using a specific radioimmunoassay.
      Furthermore, we analysed the effects of the non-selective (A/B) endothelin
      receptor antagonist, bosentan (6 and 100 mg kg-1 day-1) on mean arterial blood
      pressure, water and sodium excretion and glomerular filtration rate. 2. Our study
      revealed an overexpression of the endothelin B receptor (ETB) in the renal
      medulla of rats with liver cirrhosis (Cir: 2775 +/- 299 fmol mg-1; Con: 1695 +/-
      255 fmol mg-1; n = 8; means +/- s.d., P < 0.01), whereas the density of ETB in
      the cortex and the endothelin A receptor (ETA) in the cortex and medulla were
      similar in both cirrhotic and control rats. Receptor autoradiography showed that
      the upregulation of medullary ETB in cirrhotic rats was due to an upregulation of
      ETB in the inner medullary collecting duct cells. 3. The tissue endothelin-1
      concentrations were increased in the renal medulla of cirrhotic rats (Cir: 271 +/
      68 pg g-1wet wt.; Con: 153 +/- 36 pg g-1 wet wt., n = 8; means +/- s.d., P <
      0.01). 4. The glomerular filtration rate was slightly decreased in cirrhotic rats
      but not altered after bosentan treatment in either cirrhotic or control rats.
      Bosentan decreased sodium excretion to a similar extent in both cirrhotic and
      control rats, whereas water excretion was significantly reduced by both dosages
      of bosentan in cirrhotic rats only (Cir + vehicle: 12.5 +/- 0.62 m day-1, Cir + 6
      mg kg-1 day-1 bosentan: 8.6 +/- 1.0 ml day-1; Cir + 100 mg kg-1 day-1 bosentan:
      7.4 +/- 0.6 ml day-1; n = 10; means +/- s.e.mean). 5. We therefore suggest that
      the upregulation of the medullary ETB in cirrhotic rats is involved in the
      regulation of water excretion in rats with CCl4-induced liver cirrhosis.

PMID- 8735619
TI  - Endogenous inotropic factor-induced endothelium-dependent relaxation of vascular
      smooth muscle.
AB  - 1. Possible contractile or relaxation effects of an endogenous inotropic factor
      (EIF) isolated and purified from porcine heart left ventricle were examined in
      rat isolated aortic ring preparations. 2. EIF induced a dose-dependent relaxation
      of the rat isolated aortic ring preparation pre-contracted with 0.4 microM
      phenylephrine (PE); 200 microliters (in 5 ml bath) of EIF caused relaxation of
      aortic rings by as much as 67.4 +/- 4.5%. In another set of experiments, in the
      presence of 100 microliters EIF, the PE concentration-response contractile curve
      shifted to the right, the maximal contractile force was reduced by as much as
      32.8% and the EC50 of PE increased from 0.2 to 0.3 microM. 3. The relaxation
      effect of EIF was demonstrated to be endothelium-dependent. Additional
      experiments demonstrated that EIF-induced relaxation in an isolated aortic ring
      could be inhibited by 2 microM NG-nitro-L-arginine methyl ester, a nitric oxide
      synthase inhibitor, suggesting the involvement of nitric oxide in EIF-induced
      relaxation of the muscle. 4. Atropine (0.2 microM) or indomethacin (10 microM)
      had no significant effect on EIF-induced relaxation. 5. These data suggest that
      EIF, a novel endogenous inotrope from porcine myocardium, also acts as an
      endothelium-dependent vasodilator substance mediating relaxation in the rat
      isolated aorta mainly by release of nitric oxide. The possibility of EIF acting
      through muscarinic receptor and the involvement of prostacyclin were excluded.

PMID- 8735620
TI  - Rhythmic relaxations of active tension in the rabbit large arteries induced by a
      combination of cyclopiazonic acid and Bay K 8644.
AB  - 1. We previously demonstrated that cyclopiazonic acid (CPA), an inhibitor of
      Ca(2+)-ATPase in the sarcoplasmic reticulum, induced rhythmic relaxations of
      active tension in the endothelium-denuded small arteries of the mesentery and the
      ear of the rabbit, but that this agent failed to induce rhythmic responses in the
      endothelium-denuded rabbit femoral artery. 2. In the present study, an attempt
      was made to induce rhythmic relaxations of active tension in the endothelium
      denuded rabbit femoral artery and the thoracic aorta, both of which were
      suspended in organ chambers for isometric tension recordings, by using CPA plus
      Bay K 8644, an L-type Ca2+ channel agonist, to induce an excessive increase in
      cytosolic Ca2+. 3. CPA or Bay K 8644 alone failed to produce rhythmic relaxations
      in the femoral artery that had been contracted with phenylephrine. In contrast,
      rhythmic responses were induced by the sequential treatment of the femoral artery
      with CPA and Bay K 8644. 4. The rhythmic relaxations of active tension in the
      femoral artery induced by CPA plus Bay K 8644 were inhibited by charybdotoxin and
      by iberiotoxin, both of which are antagonists of the Ca(2+)-activated K+ channel,
      but not by glibenclamide, a blocker of the ATP-sensitive K+ channel. 5. The
      endothelium-denuded rabbit aorta also exhibited rhythmic responses by the
      sequential addition of CPA and Bay K 8644. These responses were sensitive to
      charybdotoxin. 6. These findings indicate that, like small arteries, the large
      femoral and aortic arteries of the rabbit are also capable of displaying rhythmic
      relaxations of active tension; these relaxations may be in part attributed to the
      activation of the Ca(2+)-activated K+ channel as a result of the Ca2+ overload
      caused by CPA and Bay K 8644.

PMID- 8735621
TI  - Reversal by NPY, PYY and 3-36 molecular forms of NPY and PYY of intracisternal
      CRF-induced inhibition of gastric acid secretion in rats.
AB  - 1. The Y receptor subtype involved in the antagonism by neuropeptide Y (NPY) of
      intracisternal corticotropin-releasing factor (CRF)-induced inhibition of gastric
      acid secretion was studied in urethane-anaesthetized rats by use of peptides with
      various selectivity for Y1, Y2 and Y3 subtypes: NPY, a Y1, Y2 and Y3 agonist,
      peptide YY (PYY), a Y1 and Y2 agonist, [Leu31, Pro34]-NPY, a Y1 and Y3 agonist,
      NPY(3-36) and PYY(3-36), highly selective Y2 agonists and NPY(13-36) a weak Y2
      and Y3 agonist. Peptides were injected intracisternally 10 min before
      intracisternal injection of CRF (10 micrograms) and gastric acid secretion was
      measured by the flushed technique for 1 h before and 2 h after pentagastrin-(10
      micrograms kg-1 h-1, i.v.) infusion which started 10 min after CRF injection. 2.
      Intracisternal injection of CRF (10 micrograms) inhibited by 56% gastric acid
      secretion stimulated by pentagastrin. Intracisternal injection of NPY and PYY
      (0.1-0.5 microgram) did not influence the acid response to pentagastrin but
      blocked CRF-induced inhibition of pentagastrin-stimulated acid secretion. NPY(3
      36) (0.5 microgram) and PYY(3-36) (0.25 and 0.5 microgram) also completely
      blocked the inhibitory action of CRF on pentagastrin-stimulated acid secretion.
      3. [Leu31, Pro34]-NPY (0.5-5 micrograms) and NPY(13-36) (0.5-5 micrograms)
      injected intracisternally did not modify gastric acid secretion induced by
      pentagastrin or CRF inhibitory action. 4. The sigma antagonist, BMY 14802 (1 mg
      kg-1, s.c.) did not influence the acid response to pentagastrin but prevented the
      antagonism by PYY(3-36) (0.5 microgram) of the CRF antisecretory effect. 5. These
      results show that both PYY and NPY and the 3-36 forms of PYY and NPY are
      equipotent in blocking central CRF-induced inhibition of pentagastrin-stimulated
      gastric acid secretion. The structure-activity profile suggests a mediation
      through Y2 receptor subtype and the involvement of sigma binding sites.

PMID- 8735622
TI  - Cerebrovascular responsiveness to NG-nitro-L-arginine methyl ester in
      spontaneously diabetic rats.
AB  - 1. There is evidence that endothelial dysfunction is associated with diabetes
      mellitus. The purpose of the present study was to assess local cerebral blood
      flow (LCBF) and cerebrovascular responsiveness to the NOS inhibitor NG-nitro-L
      arginine methyl ester (L-NAME) in spontaneously diabetic insulin-dependent
      BioBred (BB) rats. 2. Diabetic rats, and non-diabetic controls, were treated with
      L-NAME (30 mg kg-1, i.v.) or saline, 20 min prior to the measurement of LCBF by
      the fully quantitative [14C]-iodoantipyrine autoradiographic technique. 3. There
      were no significant differences in physiological parameters (blood pH, PCO2, and
      PO2, rectal temperature, arterial blood pressure, or plasma glucose) between any
      of the groups of rats, and no difference in either the extent or the temporal
      characteristics of the hypertensive response to L-NAME between diabetic and non
      diabetic rats. 4. In diabetic rats, a global reduction in basal LCBF was
      observed, although significant reductions (between -20 and -30%) were found in
      only 5 (mainly subcortical) out of the 13 brain regions measured. Following L
      NAME injection, significant reductions in LCBF (between -20 and -40%) were found
      in the non-diabetic animals. In diabetic animals treated with L-NAME, a
      significant reduction in LCBF was measured only in the hypothalamus (-33%). 5.
      The cerebrovascular response to acute L-NAME is attenuated in spontaneously
      diabetic insulin-dependent BB rats. This would be consistent with the endothelial
      dysfunction in cerebral vessels, known to be associated with diabetes mellitus
      and it is possible that a loss of NO-induced dilator tone, amongst other factors,
      may underlie the observed reductions of basal LCBF in these animals.

PMID- 8735623
TI  - Effects of ranolazine on L-type calcium channel currents in guinea-pig single
      ventricular myocytes.
AB  - 1. Ranolazine has protective effects against ischaemia as exemplified by a
      reduction of the associated enzyme release and an attenuation of the fall of ATP
      and other metabolic changes. It has been suggested that ranolazine may affect GTP
      binding proteins involved in the beta-adrenergic protein kinase A (PKA) cascade
      by interacting with Gs. Calcium channel currents are stimulated by this cascade
      but the effect of ranolazine upon them is not known. The whole cell patch clamp
      technique was used to examine the action of ranolazine on basal calcium channel
      currents and those stimulated by activation at various steps in the PKA cascade.
      2. Ranolazine had only a small effect on the basal calcium current (100 microM
      caused 11.3% inhibition), but markedly attenuated the beta-adrenoceptor
      stimulated current (20 nM isoprenaline increased current by 2.3 fold, 10 microM
      ranolazine inhibited this increase by 47.6%). When the PKA cascade was activated
      downstream to the receptor by either G-protein activation with Gpp[NH]p or
      adenylate cyclase activation with forskolin, the calcium current showed a
      sensitivity to ranolazine similar to the basal current. Activation of the PKA
      cascade via H2 receptors gave rise to currents which showed an intermediate
      sensitivity to ranolazine. Ranolazine inhibition of ICa persisted during
      muscarinic attenuation of beta-adrenoceptor activation. 3. The results indicate
      that ranolazine, at concentrations which have significantly beneficial effects
      during ischaemic episodes, only greatly affects whole cell calcium current when
      facilitated by beta-adrenoceptor or histamine receptor activation. Ranolazine
      would appear to act at the receptor level, rather than at the GTP-binding or
      Gs/adenylate cyclase level. An additional smaller effect is also present, which
      may be mediated by a direct effect on the channel, or components closely
      associated with it.

PMID- 8735624
TI  - Improvement by dynorphin A (1-13) of galanin-induced impairment of memory
      accompanied by blockade of reductions in acetylcholine release in rats.
AB  - 1. Human galanin (0.32 nmol per rat, i.c.v.), an endogenous neuropeptide,
      administered 30 min before acquisition or retention trials, significantly
      impaired the acquisition of learning and recall of memory in a step-through type
      passive avoidance performance. 2. The role of dynorphin A (1-13) in learning and
      memory is controversial. Dynorphin A (1-13) (0.5 nmol per rat, i.c.v.)
      administered 5 min before galanin injection, completely antagonized these
      impairments. 3. Galanin significantly decreased acetylcholine release in the
      hippocampus 40 to 120 min after injection as determined by in vivo brain
      microdialysis. This peptide also decreased acetylcholine release, albeit to a
      lesser extent, from the frontal cortex. 4. Dynorphin A (1-13) (0.5 nmol per rat,
      i.c.v.) 5 min before galanin injection, completely blocked the decrease in
      extracellular acetylcholine concentration induced by galanin. 5. These
      antagonistic effects of dynorphin A (1-13) were abolished by treatment with
      norbinaltorphimine (5.44 nmol per rat, i.c.v.), a selective kappa-opioid receptor
      antagonist, 5 min before dynorphin A (1-13). 6. Dynorphin A (1-13) (0.5 nmol)
      itself had no effect on learning and memory and on the acetylcholine
      concentration in the hippocampus or the frontal cortex in normal rats. 7. These
      results suggest that the neuropeptide dynorphin A (1-13) ameliorates the galanin
      induced impairment of learning and memory accompanied by abolition of reductions
      in acetylcholine release via kappa-opioid receptors.

PMID- 8735625
TI  - Attenuation of endotoxin-induced multiple organ dysfunction by 1-amino-2-hydroxy
      guanidine, a potent inhibitor of inducible nitric oxide synthase.
AB  - 1. We have investigated the effects of (i) several guanidines on the activity of
      the inducible isoform of nitric oxide (NO) synthase (iNOS) in murine cultured
      macrophages and rat aortic vascular smooth muscle cells (RASM); and (ii) 1-amino
      2-hydroxy-guanidine, the most potent inhibitor of iNOS activity discovered, on
      haemodynamics, multiple organ (liver, renal, and pancreas) dysfunction and iNOS
      activity in rats with endotoxic shock. 2. The synthesized guanidine analogues
      caused concentration-dependent inhibitions of the increase in nitrite formation
      caused by lipopolysaccaride (LPS, 1 microgram ml-1) in J774.2 macrophages and
      RASM cells with the following rank order of potency: 1-amino-2-hydroxy-guanidine
      > 1-amino-2-methyl-guanidine > 1-amino-1-methyl-guanidine > 1-amino-1,2-dimethyl
      guanidine. Interestingly, 1-amino-2-hydroxy-guanidine (IC50: J774.2, 68 microM;
      RASM, 114 microM) was more potent in inhibiting nitrite formation caused by LPS
      than NG-methyl-L-arginine, but less potent than aminoethyl-isothiourea. 3. In the
      anaesthetized rat, LPS caused a fall in mean arterial blood pressure (MAP) from
      115 +/- 4 mmHg (time 0) to 98 +/- 5 mmHg at 2 h (P < 0.05, n = 10) and 69 +/- 5
      mmHg at 6 h (P < 0.05, n = 10). The pressor effect of noradrenaline (NA, 1 mg kg
      1, i.v.) was also significantly reduced at 1 to 6 h after LPS (vascular
      hyporeactivity). Treatment of LPS-rats with 1-amino-2-hydroxy-guanidine (10 mg kg
      1, i.v. plus 10 mg kg-1 h-1 starting at 2 h after LPS) prevented the delayed
      hypotension and vascular hyporeactivity seen in LPS-rats. However, 1-amino-2
      hydroxy-guanidine had no effect on either MAP or the pressor effect elicited by
      NA in rats infused with saline rather than LPS. 4. Endotoxaemia for 6 h caused a
      significant rise in the serum levels of aspartate or alanine aminotransferase
      (i.e. GOT or GPT) and bilirubin, and hence, liver dysfunction. Treatment of LPS
      rats with 1-amino-2-hydroxy-guanidine significantly attenuated the liver
      dysfunction caused by LPS (P < 0.05, n = 10). Injection of LPS also caused a
      rapid (almost maximal at 2 h) increase in the serum levels of urea and
      creatinine, and hence, renal dysfunction. This renal dysfunction was not affected
      by 1-amino-2-hydroxy-guanidine (P > 0.05; n = 10). Endotoxaemia also caused a
      dysfunction of pancreas (rise in serum levels of lipase) as well as a metabolic
      acidosis (falls in PCO2, HCO3 and base excess). Both pancreatic dysfunction and
      metabolic acidosis were largely attenuated by treatment of LPS-rats with 1-amino
      2-hydroxy-guanidine. In rats infused with saline rather than LPS, 1-amino-2
      hydroxy-guanidine had no effect on liver, renal or pancreatic function (n = 4).
      5. Endotoxaemia for 6 h resulted in a rise in the serum levels of nitrite (11.0
      +/- 0.8 microM, P < 0.01, n = 10), which was significantly reduced by 1-amino-2
      hydroxy-guanidine (6.5 +/- 0.7 microM, P < 0.05, n = 10). Endotoxaemia for 6 h
      was also associated with a significant increase in iNOS activity in lung and
      liver, which was significantly reduced in lung or liver homogenates obtained from
      LPS-rats treated with 1-amino-2-hydroxy-guanidine. In addition, endotoxaemia for
      6 h resulted in a significant increase in myeloperoxidase activity (MPO), an
      indicator of neutrophil infiltration, in the liver. Treatment of LPS-rats with 1
      amino-2-hydroxy-guanidine did not affect the rise in MPO-activity in the liver
      caused by endotoxin. 6. Thus, 1-amino-2-hydroxy-guanidine is a potent inhibitor
      of iNOS activity in macrophages or RASM in culture as well as in rats with
      endotoxic shock. Inhibition of iNOS activity with 1-amino-2-hydroxy-guanidine
      prevents the delayed circulatory failure and attenuates the dysfunction of liver,
      and pancreas, as well as the metabolic acidosis caused by endotoxaemia.

PMID- 8735626
TI  - Comparison of desulfatohirudin (REVASC) and heparin as adjuncts to thrombolytic
      therapy with reteplase in a canine model of coronary thrombosis.
AB  - 1. We compared the direct thrombin inhibitor, desulfatohirudin (REVASC) and the
      indirect thrombin inhibitor, heparin, as adjuncts to thrombolytic therapy with
      reteplase in a canine model of coronary artery thrombosis. 2. Reteplase (BM
      06.022) is a recombinant unglycosylated variant of human tissue-type plasminogen
      activator. Thrombus formation in anaesthetized open chest dogs was induced by
      electrical injury. Left circumflex coronary artery blood flow was monitored for
      210 min with an electromagnetic flow probe. Twenty eight dogs were randomized to
      receive i.v. heparin (120 iu kg-1 bolus plus 80 iu kg-1 per h) or i.v. hirudin
      (2.0 mg kg-1 bolus plus 2.0 mg kg-1 per h) 10 min before thrombolysis preceded by
      i.v. acetylsalicyclic acid (20 mg kg-1) 5 min prior to anticoagulation. Every dog
      received an i.v. double bolus injection of 0.14 + 0.14 u kg-1 ( = 0.24 + 0.24 mg
      kg-1) reteplase, 30 min apart, 1 h after thrombus formation. 3. At comparable
      reperfusion rates (12 out of 12 vs. 15 out of 16 dogs), hirudin enhanced time to
      reperfusion (14.3 +/- 1.4 vs. 23.2 +/- 3.4 min; P < 0.05) and completely
      prevented reocclusion after reperfusion in contrast to heparin (0 out of 11 vs. 7
      out of 11 dogs; P < 0.05). Coronary blood flow quality was improved by hirudin as
      shown by a higher maximum blood flow after reperfusion (130 +/- 14.3 vs. 83 +/-
      9.3% of baseline; P < 0.05), a higher blood flow level at 20, 30, 40, and 50 min
      after onset of thrombolysis (P < 0.05) and a longer cumulative patency time (195
      +/- 1.7 vs. 166 +/- 12 min; P < 0.05). Activated partial thromboplastin time and
      buccal mucosa bleeding time were prolonged (P < 0.05) by either anticoagulant,
      but did not differ significantly between groups. 4. The direct thrombin
      inhibitor, desulfatohirudin, enhanced thrombolysis, prevented reocclusion and
      increased blood flow as compared with the indirect thrombin inhibitor, heparin,
      when investigated at one dose level each and used in conjunction with reteplase.

PMID- 8735627
TI  - Role of protein kinase C in mesenteric pressor responses of rats with portal
      hypertension.
AB  - 1. Hyporesponsiveness to vasoconstrictors is a characteristic abnormality of
      liver diseases of uncertain origin. In the present study, we have evaluated the
      involvement of protein kinase C (PKC) in the reduced pressor response to
      methoxamine (MTX) of a rat model of portal hypertension induced by partial portal
      vein ligation (PVL). Experiments were performed in the isolated and perfused
      mesentery. 2. The pressor response to MTX was reduced in PVL compared to that of
      control animals (Sham) and pretreatment with NG-nitro-L-arginine (L-NOARG, 10(-4)
      M) or removal of the endothelium potentiated the response of both groups.
      However, only removal of the endothelium completely eliminated the reduced
      pressor response to MTX of the PVL vessels. 3. Pretreatment of the mesentric
      vessels with calphostin C (10(-6) M), a PKC inhibitor, reduced the response to
      MTX of Sham to a level similar to that of untreated PVL vessels, but did not
      change that of PVL animals. 4. Mesenteric pressor responses to a PKC activator,
      phorbol 12,13-dibutyrate (PDBu), were similar in vessels from both PVL and Sham
      rats and pretreatment with L-NOARG or removal of the endothelium enhanced those
      responses while indomethacin (10(-5) M) decreased them. In all cases, the
      responses to PDBU were similar in PVL vessels compared to Sham. 5. These results
      indicate that the reduced pressor response to MTX of the mesenteric vascular bed
      of PVL rats is due to an endothelial alteration, compatible with an enhanced
      production of nitric oxide. The lack of response to calphostin C in PVL vessels
      suggests an impairment in agonist-induced PKC activation. Since direct activation
      of PKC induces a normal pressor response, it is concluded that the endothelial
      alteration interacts with the mechanism producing PKC activation, which results
      in a lower pressor response of the PVL mesenteric vaculature.

PMID- 8735628
TI  - Rat striatal muscarinic receptors coupled to the inhibition of adenylyl cyclase
      activity: potent block by the selective m4 ligand muscarinic toxin 3 (MT3).
AB  - 1. In rat striatal membranes, muscarinic toxin 3 (MT3), a selective ligand of the
      cloned m4 receptor subtype, antagonized the acetylcholine (ACh) inhibition of
      forskolin- and dopamine D1 receptor-stimulated adenylyl cyclase activities with
      pA2 values of 8.09 and 8.15, respectively. 2. In radioligand binding experiments,
      MT3 increased the Kd but did not change the Bmax value of [3H]-N
      methylscopolamine (3H]-NMS) binding to rat striatal muscarinic receptors. The
      toxin displaced the major portion of the [3H]-NMS binding sites with a Ki of 8.0
      nM. 3. In rat myocardium, MT3 antagonized the ACh inhibition of adenylyl cyclase
      with a Ki value of 860 nM. 4. In rat cerebral cortical membranes prelabelled with
      [3H]-myo-inositol, MT3 counteracted the methacholine stimulation of [3H]-inositol
      phosphates formation with a Ki value of 113 nM. 5. The present study shows that
      MT3 is a potent antagonist of the striatal muscarinic receptors coupled to
      inhibition of adenylyl cyclase activity. This finding provides strong evidence
      for the classification of these receptors as pharmacologically equivalent to the
      m4 gene product (M4). On the other hand, the weaker potencies of MT3 in
      antagonizing the muscarinic responses in cerebral cortex and in the heart are
      consistent with the reported lower affinities of the toxin for the cloned m1 and
      m2 receptor subtypes, respectively.

PMID- 8735629
TI  - Receptors for kinins in the human isolated umbilical vein.
AB  - 1. The human umbilical vein has been found to contract in response to bradykinin
      (BK) and desArg9BK. 2. The rank order of potency of agonists, in the presence of
      the B1 receptor antagonist Lys[Leu8]desArg9BK, is as follows: [Hyp3, Tyr(Me)8]BK
      (pD2 8.88) = [Hyp3]BK (pD2 8.86) = LysBK (pD2 8.81) > or = BK (pD2 8.60) >>
      [Aib7]BK (pD2 6.38) >> desArg9BK and LysdesArg9BK (inactive). 3. Hoe 140 (pA2
      8.42) inhibits the effects of BK while other B2 receptor peptide antagonists are
      very weak and WIN 64338 is practically inactive. 4. Venoconstrictor responses to
      desArg9BK of fresh tissues increase with time during the in vitro incubation and
      reach a maximum after 4-6 h. The activity of Hoe 140 (pA2 5.48) is negligible
      against B1 receptor agonists. 5. When measured in the presence of the selective
      B2 receptor antagonist Hoe 140 (400 nM), the order of potency of kinin related
      peptides on the B1 receptor is Lys[desArg9]BK (pD2 8.60) > desArg9BK (pD2 6.69).
      BK, LysBK, [Hyp3]BK and other B2 receptor agonists are inactive. 6. The B1
      receptor antagonist, Lys[Leu8]desArg9BK (pA2 7.99), inhibits the response of the
      human vein to B1 receptor agonists (LysdesArg9BK or desArg9BK), but do not alter
      the effect of BK. 7. The results summarized in this paper indicate that the human
      isolated umbilical vein is a sensitive preparation containing both B1 and B2
      receptors. The human B2 receptor shows some similarity with that of the rabbit
      (at least for agonist potencies) and differs from the B2 receptor of the guinea
      pig. Compared to the rabbit B1 receptor, the human B1 receptor shows low
      sensitivity to peptides that lack the N-terminal Lys.

PMID- 8735630
TI  - The effect of a tachykinin NK1 receptor antagonist, SR140333, on oedema formation
      induced in rat skin by venom from the Phoneutria nigriventer spider.
AB  - 1. The possibility that tachykinin NK1 receptors are involved in the plasma
      extravasation evoked by intradermal (i.d.) injection of Phoneutria nigriventer
      venom (PNV) in rat dorsal skin in vivo has been investigated. 2. Local oedema
      formation induced by the i.d. injection of test agents was measured by the
      extravascular accumulation of intravenously (i.v.) injected 125I-labelled human
      serum albumin over a 30 min period. 3. The tachykinin NK1 agonist, GR73632 (30
      pmol per site), induced local oedema formation which was potentiated by co
      injection with the neuropeptide vasodilator, calcitonin gene-related peptide
      (CGRP, 10 pmol per site). The non-peptide tachykinin NK1 receptor antagonist,
      SR140333 (0.03-1 nmol per site co-injected, i.d.) significantly inhibited (0.3
      nmol per site, P < 0.05; 1 nmol per site, P < 0.001) local oedema formation
      induced by GR73632 with CGRP but not that induced by histamine (10 nmol per site)
      with CGRP. 4. PNV (0.03-0.3 microgram per site) injected i.d. induced dose
      dependent local oedema formation. SR140333 (1 nmol per site, co-injected i.d.)
      inhibited oedema formation; with complete inhibition observed at doses of 0.03
      microgram (P < 0.05) and 0.1 microgram (P < 0.001); and partial inhibition (50%)
      observed with the highest dose of PNV, 0.3 microgram (P < 0.05). 5. Local oedema
      formation induced by PNV was not affected by systemic pretreatment with the
      bradykinin B2 receptor antagonist, Hoe 140 (80 nmol kg-1, i.v.), which was used
      at a dose which significantly inhibited oedema formation by bradykinin (1 nmol
      per site). 6. Local oedema formation induced by PNV was significantly inhibited
      (P < 0.01) by co-injection of the histamine H1 receptor antagonist, mepyramine
      (2.5 nmol per site), together with the 5-hydroxytryptamine (5-HT) antagonist,
      methysergide (2.8 nmol per site). 7. In the presence of all three antagonists
      (mepyramine 2.5 nmol per site; methysergide, 2.8 nmol per site and SR140333 1
      nmol per site), the plasma extravasation induced by PNV was further significantly
      inhibited (P < 0.001, when compared with PNV injected i.d. alone; P < 0.05 when
      compared with PNV co-injected with mepyramine and methysergide and P < 0.01, when
      compared with PNV co-injected with SR140333). 8. These results suggest that
      oedema formation evoked by i.d. PNV in rat skin may be partially mediated via a
      mechanism involving tachykinin NK1 receptors and that this effect is independent
      of histamine and 5-HT.

PMID- 8735631
TI  - Analysis of the activity of alpha 1-adrenoceptor antagonists in rat aorta.
AB  - 1. In this study, the effect of seven alpha 1-adrenoceptor antagonists
      (tamsulosin, phentolamine, prazosin, WB-4101, 5-methylurapidil, spiperone and
      HV723) have been examined on the contractile response to noradrenaline (NA) and
      phenylephrine (PE) in rat isolated aorta. 2. NA and PE, when administered using a
      cumulative dosing schedule, both produced concentration-dependent contraction of
      aortic rings. It was possible to fit the individual concentration-effect (E/[A])
      curve data to the Hill equation to provide estimates of the curve midpoint
      location (p[A]50 = 7.74 +/- 0.10 and 7.14 +/- 0.18), midpoint slope (nH = 0.82 +/
      0.03 and 0.99 +/- 0.10) and upper asymptote (alpha = 3.2 +/- 0.3 and 3.1 +/- 0.2
      g) parameters for NA and PE, respectively. However, the Hill equation provided a
      better fit to the E/[A] curve data obtained with another contractile agent, 5
      hydroxytryptamine (5-HT) (p[A50] = 6.09 +/- 0.08, nH = 1.49 +/- 0.09, alpha = 2.6
      +/- 0.3 g), as judged by calculation of the mean sum of squares of the
      differences between the observed and predicted values. 3. All of the antagonists
      investigated produced concentration-dependent inhibition of the contractile
      responses of the aorta to NA and PE. Although no significant effects on the upper
      asymptotes of the E/[A] curves of any of the antagonists tested were detected,
      only tamsulosin and 5-methylurapidil did not have a significant effect on the
      slope (nH) of the NA and PE E/[A] curves. The other antagonists produced
      significant steepening of the curves obtained with NA and/or PE. 4.
      Notwithstanding the fact that one of the basic criteria for simple competitive
      antagonism at a single receptor class was not always satisfied, the individual
      log [A]50 values estimated in the absence and presence of antagonist within each
      experiment were fitted to the competitive model. The Schild plot slope parameters
      for the antagonism of NA and PE by phentolamine and HV723 were found to be
      significantly less than unity. The Schild plot slope parameters for the other
      antagonists were not significantly different from unity. 5. In the absence of
      evidence to suggest that the deviations from simple competitive antagonism were
      due to failure to satisfy basic experimental conditions for quantitative
      analysis, an attempt was made to see whether the data could be accounted for by
      an existing two-receptor model (Furchgott, 1981). The goodness-of-fit obtained
      with the two-receptor model was significantly better than that obtained with the
      one-receptor model. Furthermore, with the exception of the data obtained with
      phentolamine, the pKB estimates for the two receptors were independent of whether
      NA or PE was used as agonist. 6. To determine which alpha 1-adrenoceptor subtypes
      may be associated with those defined by the two receptor model, the mean pKB
      estimates obtained from the two-receptor model fit were compared with affinities
      measured by Laz et al. (1994) for rat cloned alpha 1-adrenoceptor subtypes
      expressed in COS-7 cells. The sum of squared differences of the data points from
      the line of identity was smallest for both pKB1 and pKB2 in the case of the alpha
      1a/d-adrenoceptor (now referred to as alpha 1d-adrenoceptor; Hieble et al.,
      1995). Therefore, the complexity exposed in this study may be due to the
      expression of closely-related forms of the alpha 1d-adrenoceptor. However,
      relatively good matches were also found between pKB1 and alpha 1c and between
      pKB2 and alpha 1b. Therefore, on the basis of these data, it is not possible to
      rule out the involvement of all three alpha 1-adrenoceptors. The conflicting
      reports concerning the characteristics of the alpha 1-adrenoceptor population
      mediating contraction of the rat aorta may, at least in part, be due to the lack
      of highly selective ligands and to between-assay variation in the expression of
      multiple alpha 1-adrenoceptors.

PMID- 8735632
TI  - Coupling of metabotropic glutamate receptors to phosphoinositide mobilisation and
      inhibition of cyclic AMP generation in the guinea-pig cerebellum.
AB  - 1. The effects of metabotropic glutamate receptor (mGluR) agonists on cyclic
      nucleotide and phosphoinositide turnover were investigated in adult guinea-pig
      cerebellar slices by use of radioactive precursors. 2.L-Glutamate, 1
      aminocyclopentane-1S,3R-dicarboxylate (1S,3R-ACPD) and RS-3,5
      dihydroxyphenylglycine (DHPG) evoked concentration-dependent increases in the
      accumulation of [3H]-inositol phosphates with pEC50 values of 2.98 +/- 0.02, 4.45
      +/- 0.06 and 4.47 +/- 0.07, respectively. Maximal responses to these agents were
      43 +/- 8, 52 +/- 12 and 84 +/- 11% of the response to 1 mM histamine,
      respectively. 3. The phosphoinositide response to 1S,3R-ACPD was antagonized in
      the presence of (+)-alpha-methyl-4-carboxyphenylglycine, with a calculated pKi
      value of 3.55 +/- 0.03. 4. Forskolin-stimulated accumulation of [3H]-cyclic AMP
      was not significantly altered in the presence of 10 microM DCG-IV or 300 microM
      1S,3R-ACPD. Similarly, 300 microM 1S,3R-ACPD failed to alter isoprenaline-(1
      microM) or 2-chloroadenosine (2-CA, 30 microM)-stimulated accumulation of [3H]
      cyclic AMP. 5. Forskolin-stimulated accumulation of [3H]-cyclic AMP was
      concentration-dependently inhibited in the presence of L-glutamate and L-serine-O
      phosphate (L-SOP) with pIC50 values of 2.91 +/- 0.17 and 2.86 +/- 0.04 with
      maximal inhibitions of 47 +/- 2 and 92 +/- 3%, respectively. L-2-Amino-4
      phosphonobuty-rate (L-AP4) inhibited the forskolin response without saturating,
      evoking an inhibition of 71 +/- 7% at 3 mM. 6. 2-CA-evoked accumulation of [3H]
      cyclic AMP was also inhibited by L-glutamate and L-SOP with pIC50 values of 2.71
      +/- 0.03 and 2.72 +/- 0.08 and maximal inhibitions of 51 +/- 5 and 99 +/- 0%,
      respectively. L-AP4 inhibited the 2-CA response without saturating, evoking an
      inhibition of 68 +/- 1% at 3 mM. 7. Isoprenaline-evoked accumulation of [3H]
      cyclic AMP was inhibited by L-glutamate and L-SOP with pIC50 values of 3.21 +/-
      0.01 and 2.96 +/- 0.08 and maximal inhibitions of 88 +/- 2 and 93 +/- 3%,
      respectively. 8. These results suggest that the guinea-pig cerebellum expresses
      Group I and Group III mGluRs coupled to phosphoinositide turnover and inhibition
      of cyclic AMP generation, respectively.

PMID- 8735633
TI  - Effects of dexamethasone and cyclosporin A on the accumulation of eosinophils in
      acute cutaneous inflammation in the guinea-pig.
AB  - 1. Eosinophils are thought to play an important role in the pathophysiology of
      allergic diseases and pharmacological suppression of their recruitment is
      considered to be of therapeutic benefit. In the present study we have assessed
      and compared the effects of treatment with dexamethasone and cyclosporin A on the
      accumulation of 111In-labelled eosinophils and local oedema formation in sites of
      acute inflammation in guinea-pig skin. 2. When injected locally 150 min prior to
      i.d. administration of antigen in a passive cutaneous anaphylactic (PCA)
      reaction, dexamethasone (10(-9) to 3 x 10(-7) mol per site) dose-dependently
      inhibited oedema formation by up to 50%. Similarly, oedema formation induced by
      PAF and lipopolysaccharide (LPS), but not by zymosan-activated plasma (ZAP), was
      significantly inhibited by dexamethasone. In contrast, 111In-eosinophil
      accumulation measured in response to i.d. injection of PAF, LPS and ZAP or in the
      PCA reaction was not altered. 3. Systemic treatment with dexamethasone (4 mg kg
      1, i.v., 150 min pretreatment period) inhibited both oedema formation and 111In
      eosinophil accumulation induced by PAF, ZAP, LPS and in the PCA reaction. 4. The
      effects of i.d. injection of cyclohexamide (2 x 10(-7) mol per site) on 111In
      eosinophil accumulation and oedema formation induced by PAF, ZAP or in a PCA
      reaction were evaluated in order to assess the dependency of these responses on
      protein synthesis. Cycloheximide had no effect on the responses measured. In
      contrast, 111In-eosinophil accumulation, but oedema formation, induced by LPS was
      inhibited by 30%. 5. Acute (10 mg kg-1, i.v., 15 min pretreatment) or prolonged
      (10 mg kg-1, s.c. daily for 3 days) systemic treatment with cyclosporin A had no
      effect on 111In-eosinophil accumulation or oedema formation induced by PAF, ZAP,
      LPS or in the PCA reaction. 6. In conclusion, we demonstrate preferential
      inhibitory effects of dexamethasone on 111In-eosinophil accumulation according to
      its site of administration. In addition we show that dexamethasone inhibits
      protein synthesis-independent acute inflammation in guinea-pig skin. Finally, our
      results do not support the concept that eosinophils are an important cellular
      site of action for the inhibitory effects of cyclosporin A in a guinea-pig model
      of allergic inflammation.

PMID- 8735634
TI  - Regional haemodynamic effects of antagonists of angiotensin II, endothelin and
      adrenoceptors in conscious, vasopressin-deficient, genetically hypertensive rats.
AB  - 1. Male, vasopressin-deficient, normotensive (DI/N) and hypertensive (DI/H) rats
      were chronically instrumented (all surgery under sodium methohexitone
      anaesthesia) to allow assessment of resting haemodynamic status and responses to
      antagonism of AT1-receptors (Experiment 1), ET(A-) and ET(B-) receptors
      (Experiment 2) or adrenoceptors (Experiment 3). 2. Before any treatment, mean
      arterial blood pressure (MAP) was higher, and hindquarters vascular conductance
      was consistently lower in all groups of DI/H rats than in DI/N rats. 3. In
      Experiment 1, losartan (10 mg kg-1 i.v.), an AT1-receptor antagonist, was given 5
      h after s.c. injection of saline, (DI/N, n = 8; DI/H, n = 8) or hyperoncotic
      polyethylene glycol, (DI/N, n = 9; DI/H, n = 9) to induce isosmotic hypovolaemia.
      In the volume-replete state, losartan caused similar small falls in MAP in the
      two groups (maximum delta MAP; DI/N, -9 +/- 2; DI/H, -15 +/- 5 mmHg), but the
      mesenteric and hindquarters vasodilatations were greater in DI/N rats. In the
      volume-depleted state the effects of losartan were augmented (delta MAP; DI/N, 
      32 +/- 3; DI/H. -31 +/- 3 mmHg), but its vasodilator effects were still greater
      in DI/N than in DI/H rats. 4. In Experiment 2, infusion of the ET(A-)ET(B
      )receptor antagonist, SB 209670 (600 micrograms kg-1 h-1; DI/N, n = 8; DI/H, n =
      9), had haemodynamic effects that were not different from those during saline
      infusion in DI/N (n = 7) and DI/H rats (n = 8). 5. In Experiment 3, sequential
      administration of the beta 2-adrenoceptor antagonist, ICI 118551 (0.2 mg kg-1
      bolus, 0.1 mg kg-1 h-1 infusion), the alpha 2-adrenoceptor antagonist, idazoxan
      (0.75 mg kg-1 bolus, 1 mg kg-1 h-1 infusion), and losartan (10 mg kg-1 bolus) had
      only slight haemodynamic effects in DI/N (n = 8) and DI/H (n = 9) rats.
      Subsequent administration of the alpha 1-adrenoceptor antagonist, prazosin (0.5
      mg kg-1 bolus, 0.8 mg kg-1 h-1 infusion) caused marked hypotension, although MAP
      was still higher in DI/H (95 +/- 4 mmHg) than in DI/N (75 +/- 4 mmHg) rats.
      However, in this circumstance there were no significant differences between
      renal, or mesenteric, or hindquarters vascular conductances in the two groups. 6.
      The results indicate that the hypertension and hindquarters vasoconstriction in
      DI/H rats is not dependent on AII or endothelin. Moreover, the relative elevation
      in MAP in DI/H persists in the presence of antagonism of beta 2, alpha 2- and
      alpha 1-adrenoceptors, in spite of no significant difference in regional vascular
      conductances.

PMID- 8735635
TI  - Failure of BQ123, a more potent antagonist of sarafotoxin 6b than of endothelin
      1, to distinguish between these agonists in binding experiments.
AB  - 1. In homogenates of human saphenous vein, [125I]-ET-1 and [125I]-S6b each
      labelled a single population of high affinity binding sites with K(D) values of
      0.64 +/- 0.11 nM and 0.55 +/- 0.08 nM respectively. Hill slopes were close to
      one. However, the density of receptors labelled by [125I]-ET-1 was significantly
      greater than that by [125I]-S6b (187.6 +/- 23.0 compared to 91.7 +/- 23.6 fmol mg
      1 protein, P < 0.02). 2. BQ123, an ET(A-)selective antagonist, inhibited specific
      [125I]-ET-1 and [125I]-S6b binding with equal affinity. BQ123 competed in a
      biphasic manner for both [125I]-ET-1 (0.1 nM) and [125I]-S6b (0.1 nM) with ET(A)
      K(D) values of 0.55 +/- 0.17 nM and 0.52 +/- 0.02 nM and ET(B) K(D) values of
      14.4 +/- 2.60 microM and 11.2 +/- 0.31 microM respectively. S6b monophasically
      inhibited 0.1 nM [125I]-ET-1 (K(D) 1.16 +/- 0.9 nM) but competed for 0.25 nM
      [125I]-ET-1 in a biphasic manner (K(D) high affinity site 1.99 +/- 0.84 nM, K(D)
      low affinity site 0.68 +/- 0.63 microM, ratio 67% : 33%). 3. BQ123 antagonized
      the vasoconstrictor responses of ET-1 with a pK(B) value of 6.47 whereas BQ123
      exhibited 50 fold higher affinity against S6b-mediated vasoconstriction with a
      pK(B) value of 8.18. Regression slopes were 0.80 +/- 0.13 and 1.08 +/- 0.11
      respectively. 4. In desensitization experiments, S6b (300 nM) did not contract
      preparations which were no longer responsive to ET-1 whereas a small contraction
      to ET-1 (300 nM) was obtained in preparations rendered unresponsive to S6b. 5.
      Medial sections of non-diseased human aorta, which express only ET(A) receptors,
      were used to compare dissociation rates of the two agonists. The time course for
      the dissociation of [125I]-ET-1 and [125I]-S6b was similar with 20-30% of each
      ligand dissociating at 4 h. 6. These data suggest that whilst BQ123, in common
      with other endothelin antagonists, is a much more potent blocker of S6b
      contractile responses than of ET-1 contractile responses, this is not reflected
      by the equal affinity of BQ123 determined in competition binding experiments
      against both [125I]-ET-1 and [125I]-S6b. This discrepancy in antagonist potency
      is probably not due to a marked difference in the rate of dissociation of [125I]
      ET-1 and [125I]-S6b from endothelin receptors. One possible explanation is that
      ET-1 is activating an additional population of receptors which may have lower
      affinity for BQ123. This is suggested by the discrepancy in receptor density
      identified by [125I]-ET-1 and [125I]-S6b.

PMID- 8735636
TI  - The mechanism of relaxation induced by atrial natriuretic peptide in the porcine
      renal artery.
AB  - 1. The mechanisms underlying the relaxation of the porcine renal artery induced
      by atrial natriuretic peptide (ANP) were investigated, using front-surface
      fluorimetry with fura-2 and receptor-coupled permeabilization by alpha-toxin. 2.
      ANP decreased the cytosolic Ca2+ concentration ([Ca2+]i) and tension during the
      contraction induced by a high external K+ solution, in a concentration-dependent
      manner. This ANP-induced decrease in [Ca2+]i during the contraction induced by
      high K+ solution was composed of two phases, an initial rapid phase, followed by
      a maintenance phase. The initial rapid decrease in [Ca2+]i, but not the
      maintained decrease in [Ca2+]i, was inhibited when the tissue was treated with
      thapsigargin, a selective Ca2+ pump inhibitor of the sarcoplasmic reticulum. When
      the tissues were treated with thapsigargin and external Ca2+ was replaced by
      Ba2+, which cannot be transported by the Ca2+ pump, ANP did not induce a decrease
      in [Ba2+]i, even though the elevation of tension induced by Ba2+ was strongly
      inhibited. 3. In the absence of extracellular Ca2+, ANP inhibited the release of
      Ca2+ from the intracellular store induced by noradrenaline (NA). 4. The [Ca2+]i
      (abscissa scale)-tension (ordinate scale) relationship observed during the
      contraction induced by various concentrations of high external K+ solution was
      shifted downwards by the addition of 10(-8) M ANP, indicating that, at any given
      [Ca2+]i, the tension generated by high K+ solution was considerably inhibited by
      the addition of 10(-8) M ANP. The [Ca2+]i-tension curve of the contraction
      obtained by the cumulative application of external Ca2+ (0-3.75 mM) during
      depolarization with 118 mM K+ solution was shifted to the left by 3 x 10(-7) M
      NA. This NA-induced [Ca2+]i-tension relationship was shifted to the right by 10(
      8) M ANP, indicating that the ANP-induced reduction of Ca(2+)-sensitivity
      operates during the contraction induced by NA. 5. In alpha-toxin-permeabilized
      preparations, ANP induced relaxation of tissues precontracted with a mixture of 3
      x 10(-7) M Ca2+, 10(-5) M guanosine 5'-triphosphate (GTP) and 10(-6) M NA. Thus a
      component of ANP-induced relaxation took place by way of a reduction in the Ca2+
      sensitivity of the myofilaments, independent of changes in [Ca2+]i. 6. These
      results indicate that ANP induces relaxation of the porcine renal artery by: (1)
      reducing [Ca2+]i mainly via the activation of the Ca2+ pumps located on the
      sarcoplasmic reticulum and sarcolemma, as well as via inhibition of agoinist
      induced release of Ca2+ from the intracellular store; and (2) decreasing the
      Ca(2+)-sensitivity of the contractile elements.

PMID- 8735637
TI  - Effects of the non-peptide, non-selective endothelin antagonist, bosentan, on
      regional haemodynamic responses to NG-monomethyl-L-arginine in conscious rats.
AB  - 1. Male, Long Evans rats (350-450 g) were chronically instrumented to allow
      monitoring of mean arterial blood pressure, heart rate and changes in renal,
      mesenteric and hindquarters haemodynamics. In the first experiment, animals (n =
      8) were given a bolus i.v. injection of the nitric oxide synthase inhibitor, NG
      monomethyl-L-arginine hydrochloride (L-NMMA; 30 mg kg-1) on four consecutive
      days. Fifteen min prior to L-NMMA administration on the fourth day, the
      endothelin, ETA-, ETB-receptor antagonist, bosentan, was injected (30 mg kg-1,
      i.v.). Relative to the response on the third day, bosentan caused 33 +/- 4%, 24
      +/- 3%, 14 +/- 3%, and 18 +/- 5% inhibition of the pressor, and renal, mesenteric
      and hindquarters vasoconstrictor effects of L-NMMA, respectively. 2. In the
      second experiment, bosentan was given 15 min before L-NMMA in a group of rats (n
      = 6) which had not received L-NMMA previously. Relative to the responses to L
      NMMA on the first day in the previous experiment, bosentan caused a 30%, 24%, 18%
      and 27% inhibition of the pressor, and renal, mesenteric and hindquarters
      vasoconstrictor effects of L-NMMA, respectively. 3. The results indicate a
      significant contribution from endothelin to the haemodynamic effects of L-NMMA in
      conscious rats. However, since our previous studies have shown the renin
      angiotensin and sympathoadrenal systems are not involved, it is likely that the
      major component of the cardiovascular response to L-NMMA in conscious rats is due
      to loss of vasodilator action of endothelial nitric oxide.

PMID- 8735638
TI  - Inhibition of glycolysis and enhanced mechanical function of working rat hearts
      as a result of adenosine A1 receptor stimulation during reperfusion following
      ischaemia.
AB  - 1. This study examined effects of adenosine and selective adenosine A1 and A2
      receptor agonists on glucose metabolism in rat isolated working hearts perfused
      under aerobic conditions and during reperfusion after 35 min of global no-flow
      ischaemia. 2. Hearts were perfused with a modified Krebs-Henseleit buffer
      containing 1.25 mM Ca2+, 11 mM glucose, 1.2 mM palmitate and insulin (100 muu ml
      1), and paced at 280 beats min-1. Rates of glycolysis and glucose oxidation were
      measured from the quantitative production of 3H2O and 14CO2, respectively, from
      [5-3H/U-14C]-glucose. 3. Under aerobic conditions, adenosine (100 microM) and the
      adenosine A1 receptor agonist, N6-cyclohexyladenosine (CHA, 0.05 microM),
      inhibited glycolysis but had no effect on either glucose oxidation or mechanical
      function (as assessed by heart rate systolic pressure product). The improved
      coupling of glycolysis to glucose oxidation reduced the calculated rate of proton
      production from glucose metabolism. The adenosine A1 receptor antagonist, 8
      cyclopentyl-1,3-dipropylxanthine (DPCPX 0.3 microM) did not alter glycolysis or
      glucose oxidation per se but completely antagonized the adenosine- and CHA
      induced inhibition of glycolysis and proton production. 4. During aerobic
      reperfusion following ischaemia, CHA (0.05 microM) again inhibited glycolysis and
      proton production from glucose metabolism and had no effect on glucose oxidation.
      CHA also significantly enhanced the recovery of mechanical function. In contrast,
      the selective adenosine A2a receptor agonist, CGS-21680 (1.0 microM), exerted no
      metabolic or mechanical effects. Similar profiles of action were seen if these
      agonists were present during ischaemia and throughout reperfusion or when they
      were present only during reperfusion. 5. DPCPX (0.3 microM), added at
      reperfusion, antagonized the CHA-induced improvement in mechanical function. It
      also significantly depressed the recovery of mechanical function per se during
      reperfusion. Both the metabolic and mechanical effects of adenosine (100 microM)
      were antagonized by the nonselective A1/A2 antagonist, 8-sulphophenyltheophylline
      (100 microM). 6. These data demonstrate that inhibition of glycolysis and
      improved recovery of mechanical function during reperfusion of rat isolated
      hearts are mediated by an adenosine A1 receptor mechanism. Improved coupling of
      glycolysis and glucose oxidation during reperfusion may contribute to the
      enhanced recovery of mechanical function by decreasing proton production from
      glucose metabolism and the potential for intracellular Ca2+ accumulation, which
      if not corrected leads to mechanical dysfunction of the postischaemic myocardium.

PMID- 8735639
TI  - The role of the endocardium in the facilitatory effect of bradykinin on
      electrically-induced release of noradrenaline in rat cardiac ventricle.
AB  - 1. The present investigation was undertaken to study the role of bradykinin in
      noradrenaline release from the ventricle of the rat induced by electrical
      stimulation. Slices of the left ventricle of adult Wistar rats with or without
      endocardium were previously loaded with 0.2 microM [3H]-noradrenaline and washed
      out before electrical stimulation was applied. 2. Bradykinin (0.1-100 nM)
      concentration-dependently increased tritium release evoked by electrical
      stimulation (EC50 = 3.5 (1.2-10.2) nM; n = 12). The angiotensin converting enzyme
      inhibitor, captopril (1 microM), which per se had no effect on tritium release,
      caused a marked enhancement of the bradykinin facilitatory effect, shifting the
      concentration-response curve of bradykinin to the left by about one log unit. The
      compound Hoe 140, a selective inhibitor of B2-bradykinin receptors, competitively
      antagonized the effect of bradykinin, indicating the involvement of these
      receptors in the action of bradykinin. 3. In endocardium-free ventricle,
      bradykinin had no effect either in the absence or in the presence of captopril.
      4. These results show that: (1) bradykinin is able to facilitate noradrenaline
      release evoked by electrical stimulation of the rat ventricle through activation
      of B2-bradykinin receptors located on endocardial cells; (2) this action of
      bradykinin which is markedly potentiated by the inhibition of the angiotensin
      converting enzyme seems to be exerted through the release of some factor which is
      formed in the endocardium and diffuses into the myocardium where it acts.

PMID- 8735640
TI  - Pharmacokinetic-haemodynamic relationships of 2-chloroadenosine at adenosine A1
      and A2a receptors in vivo.
AB  - 1. The purpose of the present study was to develop an experimental strategy for
      the quantification of the cardiovascular effects of non-selective adenosine
      receptor ligands at the adenosine A1 and A2a receptor in vivo. 2-Chloroadenosine
      (CADO) was used as a model compound. 2. Three groups of normotensive conscious
      rats received an short intravenous infusion of 1.4 mg kg-1 CADO during constant
      infusions of the A1-selective antagonist, 8-cyclopentyltheophylline (CPT; 20
      micrograms min-1 kg-1), the A2a-selective antagonist, 8-(3-chlorostyryl) caffeine
      (CSC; 32 micrograms min-1 kg-1) or the vehicle. The heart rate (HR) and mean
      arterial blood pressure (MAP) were recorded continuously during the experiment
      and serial arterial blood samples were taken for analysis of drug concentrations.
      The ratio MAP/HR was also calculated, which may reflect changes in total
      peripheral resistance on the assumption that no changes in stroke volume occur.
      3. During the infusion of CPT, CADO produced a reduction in both blood pressure
      and MAP/HR by activation of the A2a receptor. The concentration-effect
      relationships were described according to the sigmoidal Emax model, yielding
      potencies based on free drug concentrations (EC50,u) of 61 and 68 ng ml-1 (202
      and 225 nM) for the reduction of blood pressure and MAP/HR, respectively. During
      the infusion of CSC, an EC50,u value of 41 ng ml-1 (136 nM) was observed for the
      A1 receptor-mediated reduction in heart rate. The in vivo potencies correlated
      with reported receptor affinities (Ki(A1) = 300 nM and Ki(A2a) = 80 nM). The
      maximal reductions in MAP/HR and heart rate were comparable to those of full
      agonists, with the Emax values of -12 +/- 1 x 10(-2) mmHg b.p.m.-1 and -205
      b.p.m. respectively. 4. It is concluded that this integrated pharmacokinetic
      pharmacodynamic approach can be used to obtain quantitative information on the
      potency and intrinsic activity of new non-selective adenosine receptor agonists
      at different receptor subtypes in vivo.

PMID- 8735641
TI  - Actions of long chain alcohols on GABAA and glutamate receptors: relation to in
      vivo effects.
AB  - 1. The effects of n-alcohols on GABAA and glutamate receptor systems were
      examined, and in vitro effectiveness was compared with in vivo effects in mice
      and tadpoles. We expressed GABAA, NMDA, AMPA, or kainate receptors in Xenopus
      oocytes and examined the actions of n-alcohols on receptor function using two
      electrode voltage clamp recording. 2. The function of GABAA receptors composed of
      alpha 1 beta 1 or alpha 1 beta 1 gamma 2L subunits was potentiated by all of the
      n-alcohols studied (butanol-dodecanol). 3. In contrast to GABAA receptors,
      glutamate receptors expressed from mouse cortical mRNA or from cRNAs encoding
      AMPA (GluR3)- or kainate (GluR6)-selective subunits were much less sensitive to
      longer chain alcohols. In general, octanol and decanol were either without effect
      or high concentrations were required to produce inhibition. 4. In contrast to the
      lack of behavioural effects by long chain alcohols reported previously, decanol
      produced loss of righting reflex in short- and long-sleep mice, indicating that
      the in vivo effects of decanol may be due in part to actions at GABAA receptors.
      Furthermore, butanol, hexanol, octanol, and decanol produce similar potentiation
      of GABAA receptor function at concentrations required to cause loss of righting
      reflex in tadpoles, an in vivo model where alcohol distribution is not a
      compromising factor. 5. Thus, the in vivo effects of long chain alcohols are not
      likely to be due to their actions on NMDA, AMPA, or kainate receptors, but may be
      due instead to potentiation of GABAA receptor function.

PMID- 8735642
TI  - Preservation of endothelium-dependent relaxation in cholesterol-fed and
      streptozotocin-induced diabetic mice by the chronic administration of
      cholestyramine.
AB  - 1. Experiments were designed to investigate the effects of the low density
      lipoprotein (LDL)-lowering drugs cholestyramine on serum LDL levels and
      endothelium-dependent relaxation to acetylcholine (ACh) in cholesterol-fed or
      streptozotocin (STZ)-induced diabetic mice. 2. In aortic rings from control mice,
      ACh or A23187 caused concentration-dependent relaxation. The relaxations caused
      by ACh or A23187 were significantly attenuated in aortic rings from cholesterol
      fed and STZ-diabetic mice. The attenuated vasodilatation in both cholesterol-fed
      and diabetic mice was returned to normal by chronic administration of
      cholestyramine. The endothelium-independent relaxations of aortic rings induced
      by sodium nitroprusside (SNP) were not significantly different between control,
      cholesterol-fed and STZ-induced diabetic mice. 3. The increased LDL levels in
      cholesterol-fed and diabetic mice were returned to normal by the chronic
      administration of cholestyramine. Chronic administration of cholestyramine had no
      effects on serum glucose levels. 4. These results suggest that attenuated
      endothelium-dependent vasodilatations in both cholesterol-fed and STZ-diabetic
      mice are improved by the chronic administration of cholestyramine, and these
      effects are, at least in part, due to lowering serum LDL levels.

PMID- 8735643
TI  - Localization and activity of haem oxygenase and functional effects of carbon
      monoxide in the feline lower oesophageal sphincter.
AB  - 1. In the feline lower oesophageal sphincter (LOS), the distribution of the
      carbon monoxide (CO) producing enzymes haem oxygenase (HO)-1 and -2 was studied
      by immunohistochemistry and confocal microscopy, the HO activity was measured and
      the possible role for CO as a mediator of relaxation was investigated. 2. HO-2
      immunoreactivity was abundant in nerve cell bodies of the submucosal and
      myenteric plexus. Approximately 50% of the HO-2-containing myenteric cell bodies
      were also nitric oxide synthase- and vasoactive intestinal peptide (VIP)
      immunoreactive. In addition, HO-2 immunoreactivity was seen in nerve fibres, in
      non-neuronal cells dispersed in the smooth muscle and in arterial endothelium. HO
      1 immunoreactivity was confined to non-neuronal cells in the smooth muscle,
      similar to those positive for HO-2. 3. Activity of HO, measured as CO production,
      was observed in LOS homogenates at a rate of 1.00 +/- 0.05 nmol mg-1 protein h-1.
      This production was inhibited by the HO inhibitor, zinc protoporphyrin-IX (ZnPP).
      4. In isolated circular smooth muscle strips of LOS, developing spontaneous tone,
      exogenously administered CO evoked a concentration-dependent relaxation reaching
      a maximum of 93 +/- 3%. This relaxation was accompanied by an increase in cyclic
      GMP, but not cyclic AMP levels. The relaxant response was attenuated by methylene
      blue, but unaffected by tetrodotoxin. Repeated exposure to CO resulted in a
      progressive reduction of the relaxant response. 5. ZnPP caused a rightward-shift
      of the concentration-response curves for the relaxant responses to VIP, peptide
      histidine isoleucine, and pituitary adenylate cyclase activating peptide 27. 6.
      ZnPP and tin protoporphyrin-IX (another inhibitor of HO) did not affect
      nonadrenergic, noncholinergic relaxations induced by electrical field
      stimulation. Nor did ZnPP affect relaxations induced by 3-morpholino-sydnonimine
      or forskolin. 7. The present findings, showing localization of HO
      immunoreactivity to both neuronal and nonneuronal cells of the feline LOS,
      ability of LOS to produce CO and a relaxant effect of CO in circular LOS muscle,
      suggest a role for CO as a peripheral messenger.

PMID- 8735644
TI  - Impairment of stress adaptive behaviours in rats by the CCKA receptor antagonist,
      devazepide.
AB  - 1. Cholecystokinin (CCK) is released during stress both in limbic and
      hypothalamic areas suggesting that CCK could participate in modulating
      neuroendocrine as well as behavioural responses to stress. 2. In this study we
      have examined the effect of CCK receptor antagonists on the retention of the
      immobility response to a forced-swim stress in rats. In this test, rats are
      forced to swim during 15 min (conditioning period) and 24 h later, the duration
      of immobility is measured during a period of 5 min (re-test period). During the
      conditioning period rats display a period of vigorous activity, followed by
      progressive inactivity. During the re-test period rats remain 70-80% of the time
      in an immobile posture. 3. The CCKA receptor antagonist, devazepide (MK-329) but
      not the CCKB receptor antagonist, L-365,260, administered s.c. immediately before
      the conditioning period, decreased the duration of acquired immobility during the
      re-test period. The effect of devazepide was prevented by cholecystokinin
      octapeptide (CCK-8; 40 micrograms kg-1, s.c) as well as by the selective
      glucocorticosteroid GII receptor agonist, dexamethasone (30 micrograms kg-1,
      s.c.) 4. Neither corticosterone nor ACTH plasma levels measured both after the re
      test period and after the conditioning period were modified by devazepide
      treatment. 5. The results suggest a role for CCK in the behavioural adaptation to
      stress and indicate a relationship between CCK systems and glucocorticoids in the
      neuronal mechanisms involved in the acquisition of adaptive behaviours to stress.

PMID- 8735645
TI  - Effect of gadolinium on stretch-induced changes in contraction and
      intracellularly recorded action- and afterpotentials of rat isolated atrium.
AB  - 1. Atrial arrhythmias, like atrial fibrillation and extrasystoles, are common in
      clinical situations when atrial pressure is increased. Although cardiac
      mechanoelectrical feedback has been under intensive study for many years, the
      mechanisms of stretch-induced arrhythmias are not known in detail. This is partly
      due to methodological difficulties in recording intracellular voltage during
      stretch stimulation. In this study we investigated the effects of gadolinium
      (Gd3+), a blocker of stretch-activated (SA) channels, on stretch-induced changes
      in rat atrial action potentials and contraction force. 2. By intracellular
      voltage recordings from rat isolated atria we studied the effects of Gd3+ (80
      microM) on stretch-induced changes in action potentials. The stretch was induced
      by increasing pressure inside the atrium (1 mmHg to 7 mmHg). An elastic electrode
      holder that moved along the atrial tissue was used in the recordings. Thus the
      mechanical artifacts were eliminated and the cell-electrode contact was made more
      stable. To examine the influence of Gd3+ on atrial contraction we stretched the
      atria at different diastolic pressure levels (1 to 7 mmHg) with Gd3+ application
      of (80 microM) or diltiazem (5.0 microM). Contraction force was monitored by
      recording the pressure changes generated by the atrial contractions. 3. Our
      results show that: (1) atrial stretch induces delayed afterdepolarizations
      (DADs), increase in action potential amplitude and increase in relative
      conduction speed; (ii) Gd3+ blocks stretch-induced DADs and action potential
      changes; (iii) Gd3+ inhibits pressure-stimulated increase in the atrial
      contraction force, while similar inhibition is not observed with diltiazem, a
      blocker of L-type calcium channels. 4. This study suggests that Gd3+ inhibits
      stretch-induced changes in cell electrophysiology and contraction in the rat
      atrial cells and that the effects of gadolinium are due to rather specific block
      of stretch-activated ion channels with only a small effect on voltage-activated
      calcium channels.

PMID- 8735646
TI  - Ability of angiotensin II to modulate striatal dopamine release via the AT1
      receptor in vitro and in vivo.
AB  - 1. The ability of angiotensin II to modulate dopamine release from rat striatal
      slices in vitro and in the intact rat striatum in vivo was assessed by the
      microdialysis technique. 2. In slices of rat striatum, angiotensin II (0.1-1.0
      microM) induced a concentration-related increase in endogenous dopamine release
      which was maximal (approximately 250% above basal levels) within the first 2-4
      min of agonist application and subsequently declined to near basal values. The
      angiotensin II-induced increase in dopamine release was Ca(2+)-dependent and was
      completely antagonized by the selective AT1 receptor antagonist, losartan (1.0
      microM). In contrast, the AT2 receptor antagonist, PD123177 (1.0 microM) failed
      to modify the angiotensin II-induced response. Neither antagonist alone modified
      basal dopamine release from striatal slices. 3. In freely moving rats,
      angiotensin II (1.0-10 microM; administered via the microdialysis probe) induced
      a concentration-related increase in extracellular levels of dopamine which was
      maximal (approximately 150% above basal levels) within 20-40 min of agonist
      application and subsequently declined. The angiotensin II (10 microM)-induced
      increase in extracellular levels of dopamine was completely antagonized by the
      AT1 receptor antagonist, losartan (0.1-1.0 microM; administered via the
      microdialysis probe) but not by the AT2 receptor antagonist, PD123177 (1.0
      microM; administered via the microdialysis probe). Neither antagonist alone
      modified basal extracellular levels of dopamine. 4. Homogenate radioligand
      binding studies with [125I]-angiotensin II (0.1 nm) identified relatively low
      levels of specific binding sites in rat striatal homogenates compared to
      homogenates of pyriform cortex (51.3 +/- 9.2 and 651.3 +/- 55.1 fmol g-1 wet
      weight, respectively, mean +/- s.e.mean, n = 3; non-specific binding defined by
      unlabelled angiotensin II). The majority of the specific [125I]-angiotensin II
      (0.1 nM) binding in the striatal and pyriform cortex homogenates was sensitive to
      the selective AT1 receptor antagonist, losartan (1.0 microM). 5. In conclusions
      the present study provides direct evidence that angiotensin II acting via the AT1
      receptor subtype facilitates the release of dopamine in the rat striatum in vitro
      and in vivo. This receptor-mediated response may account for the modulation of
      dopamine-mediated behavioural responses by antagonists of the AT1 receptor and
      inhibitors of angiotensin converting enzyme.

PMID- 8735648
TI  - Discrimination by PPADS between endothelial P2Y- and P2U-purinoceptors in the rat
      isolated mesenteric arterial bed.
AB  - 1. The main aim of this study was to characterize the antagonistic effects of
      pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) at coexisting
      endothelial P2Y- and P2U-purinoceptors. Studies were conducted in Krebs-perfused
      mesenteric arterial preparations isolated from the rat, with tone raised by
      methoxamine (5-50 microM). 2. Purine and pyrimidine compounds elicited
      vasodilatation with a rank order of potency of 2-methylthio ATP (2-MeSATP) = ADP
      > ATP = UTP > P1, P3-diadenosine triphosphate (Ap3A) > P1, P2-diadenosine
      pyrophosphate (Ap2A) > NADP > adenosine. 8-para-Sulphophenyltheophylline (8-PSPT;
      3 microM) had no effect on vasodilator responses to 2MeSATP, ADP, ATP, UTP, Ap3A
      or NADP, but blocked responses to adenosine and the maximal response to Ap2A. 3.
      PPADS (3-100 microM) attenuated vasodilator responses to the P2Y-selective
      agonists 2MeSATP and ADP, shifting the dose-response curves to the right. The pA2
      values for PPADS at 2MeSATP and ADP were 5.97 +/- 0.69 and 5.98 +/- 0.86
      respectively. In contrast, PPADS had no effect on vasodilator responses mediated
      by the P2U-selective agonist, UTP, or on vasodilator responses mediated by ATP.
      4. PPADS (10 microM) was used to characterize responses mediated by the adenine
      dinucleotides; dose-response curves for vasodilator responses to Ap3A and NADP,
      but not those to Ap2A, were shifted to the right by PPADS. The estimated pA2
      values for the effect of PPADS on Ap3A and NADP were 6.38 and 6.26 respectively.
      5. Indomethacin (10 microM) had no effect on vasodilator responses to 2MeSATP,
      ADP, ATP or UTP. 6. In conclusion, these results show that PPADS is an antagonist
      at endothelial P2Y- but not P2U-purinoceptors in rat mesenteric arteries. These
      receptors cannot be discriminated by inhibition of prostaglandin synthesis; P2Y
      purinoceptors are, however, sensitive to ADP. Selective antagonism by use of
      PPADS showed that ATP acts at P2U- and not P2Y-purinoceptors. Ap3A and NADP
      mediate vasodilatation via P2Y-purinoceptors, whereas vasodilatation to Ap2A is
      mediated partly via P1- and possibly via P2U-purinoceptors.

PMID- 8735647
TI  - Prevention by (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin of both catalepsy and
      the rises in rat striatal dopamine metabolism caused by haloperidol.
AB  - 1. The influence of (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on
      haloperidol-induced increases in the dopamine metabolites, 3,4
      dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxyphenylacetic acid
      (HVA), was measured in three microdissected brain regions of the rat following a
      quantitative assessment of catalepsy. 2. Haloperidol alone (2.66 mumol kg-1,
      i.p.) caused a robust cataleptic response. Given 30 min after haloperidol, 8-OH
      DPAT (76 or 760 nmol kg-1, s.c.) prevented catalepsy in 30% and 100% of rats,
      respectively. 3. Haloperidol significantly increased the DOPAC (by 2 to 4 fold)
      and HVA (by 3 to 7 fold) contents of the caudate-putamen, nucleus accumbens and
      medial prefrontal cortex. Given alone, only the lower dose of 8-OH-DPAT caused a
      significant biochemical change, a doubling of cortical DOPAC. 4. In the cases
      where catalepsy was prevented by either dose of 8-OH-DPAT, the haloperidol
      induced increases in DOPAC and HVA were consistently lower in the caudate
      putamen. This pattern was true for the rise in cortical HVA but only in response
      to the lower dose of 8-OH-DPAT. In contrast, neither dose of 8-OH-DPAT was able
      to influence the haloperidol-induced rises in cortical DOPAC. In the nucleus
      accumbens, 8-OH-DPAT did not affect the haloperidol-induced increases in the
      dopamine metabolites, irrespective of the dose employed or the resulting
      behaviour. When catalepsy was not prevented, 8-OH-DPAT did not alter the
      neurochemical responses to haloperidol in any region. 5. These results suggest
      that part of the mechanism by which 8-OH-DPAT prevents haloperidol-induced
      catalepsy is reflected by a reversal of the compensatory increase in meso
      striatal and/or meso-cortical dopamine neuronal activity that normally
      accompanies postsynaptic dopamine receptor blockade with haloperidol.

PMID- 8735649
TI  - Vasoconstrictor responsiveness of the rat mesenteric arterial bed in cirrhosis.
AB  - 1. The effects of cirrhosis on mesenteric vascular reactivity were assessed in
      constantly perfused mesenteric arterial beds isolated from cirrhotic rats (carbon
      tetrachloride with phenobarbitone, n = 6), and from phenobarbitone-treated and
      untreated age-matched controls (n = 4,5). 2. At a constant flow rate of 5 ml min
      1 there was no difference in basal perfusion pressure between the groups.
      Electrical field stimulation (EFS; 4-32 Hz, 90V, 1 ms, 30 s) of perivascular
      nerves caused frequency-dependent increases in perfusion pressure which were not
      different between the groups. Dose-dependent vasoconstrictor responses to
      exogenous noradrenaline (NA), methoxamine (an alpha 1-adrenoceptor agonist),
      adenosine 5'-triphosphate (ATP) and vasopressin were also similar between the
      groups. 3. The nitric oxide (NO) synthesis inhibitor NG-nitro-L-arginine methyl
      ester (L-NAME; 30 microM) augmented constrictor responses to NA, EFS, methoxamine
      and vasopressin in all groups, and as shown for EFS and NA, this was reversed by
      L-arginine (300 microM). However, the maximum constrictor responses of cirrhotic
      preparations in the presence of L-NAME were significantly lower than those of
      both groups of control animals at the highest frequency of EFS (32 Hz) and
      highest doses of NA (0.15 and 0.5 mumol) and, compared to phenobarbitone-treated
      controls, methoxamine (5 mumol). Responses to ATP were significantly augmented by
      L-NAME only in the cirrhotic group. 4. A step-wise increase in perfusate flow to
      10, 15 and 20 ml min-1 produced a broadly similar increase in perfusion pressure
      within each group. At increased flow rates, cirrhotic preparations were
      hyporesponsive to NA (15 nmol) compared to the phenobarbitone-treated animals but
      not the untreated controls. Glibenclamide (5 microM) or L-NAME (30 microM) had no
      significant effect on the relationship between flow and perfusion pressure or on
      responses to NA at the different flow rates. 5. We conclude that sympathetic
      neurotransmission is unchanged in cirrhosis. Endogenous NO is important in
      modulation of constriction in both normal and cirrhotic states. Changes in NO may
      occur in cirrhosis, although the role of this in hyporesponsiveness of cirrhotic
      preparations to NA at higher flow rates and to the greater potentiation of ATP
      mediated constriction in the presence of L-NAME, together with the impact of
      factors such as changes in calcium and potassium channels, is not entirely clear.

PMID- 8735650
TI  - Metabotropic glutamate receptors in hippocampal long-term potentiation and
      learning and memory.
AB  - Glutamate receptors have been identified as important interfaces in learning and
      memory paradigms as well as in mechanisms of synaptic plasticity, such as long
      term potentiation (LTP) and long-term depression (LTD), which are believed to be
      the underlying cellular basis of at least some forms of learning. Although
      investigations of G-protein-coupled receptors have a long history, those
      depending on ligand-binding of glutamate have only been discovered recently, and
      this is the reason why our knowledge about metabotropic glutamate receptors
      (mGluRs) is at present very limited. However, the development of relatively
      specific antagonists and agonists has enabled the analysis of the role of mGluRs
      in synaptic plasticity, mostly studied on the models of LTP and LTD. Among
      others, we have been able to demonstrate that activation of mGluRs is essential
      for induction and maintenance of long-lasting hippocampal LTP in vitro and in
      vivo. The work conducted by several groups, including ours, has now provided
      compelling evidence that mGluR activation is an important step in the cellular
      cascades leading to memory formation in vertebrates. This led us to assume, given
      that the hippocampus plays a prominent role in spatial rather than discrimination
      learning, that mGluRs may participate in the processing of spatial information
      via hippocampal mechanisms, and may thus be similarly important as N-methyl-D
      aspartate receptors. This article surveys the literature dealing with mGluRs in
      hippocampal LTP and learning and memory. We will demonstrate that, although the
      understanding of cellular mechanisms of neuronal plasticity and of the
      pharmacology of learning and memory has advanced, the missing link to prove that
      LTP is a substrate for some form forms of learning still remains unsolved.
      Nevertheless, it appears reasonable to argue that mGluRs in LTP and learning may
      share some, but not all features, and it will be an interesting approach for
      further analysis to address the unresolved issues.

PMID- 8735652
TI  - Neuronally mediated anion secretion induced by short-chain fatty acids in the rat
      distal small intestine.
AB  - The short-chain fatty acids acetate, propionate and butyrate induced a
      concentration-dependent increase of short-circuit current (Isc) in the rat distal
      small intestine in vitro. They were ineffective in the proximal small intestine.
      The increase of lsc in the distal small intestine was dependent on the presence
      of Cl- and HCO3- ions. It was blocked by the inhibitor of the Na(+)-K(+)-Cl(-) 
      cotransporter, bumetanide, and by the Cl- channel blocker, 5-nitro-2-(3
      phenylpropylamino)-benzoate, indicating that short-chain fatty acids evoke an
      anion secretion. The secretion induced by propionate was blocked by the
      neurotoxin, tetrodotoxin, and inhibited by the muscarinic antagonists, atropine.
      In contrast, indomethacin, a cyclooxygenase inhibitor, or nordihydroguaiaretic
      acid, a lipoxygenase inhibitor, were ineffective. These results indicate that
      short-chain fatty acids stimulate chemosensitive neurones in the rat small
      intestine in a region-specific manner, which induce anion secretion by the
      release of mainly acetylcholine.

PMID- 8735651
TI  - cAMP-induced chloride transport in NCL-SG3 sweat gland cells.
AB  - cAMP-induced ion transport in a human sweat gland cell line, NCL-SG3, was
      investigated by X-ray microanalysis and patch-clamp technique. Stimulation with
      cAMP caused a decrease in the cellular Cl and K. cAMP had no significant effect
      on the intracellular Na and Ca. Chloride channel blockers (9-AC, DPC and NPPB)
      inhibited the cAMP-induced chloride efflux. In patch-clamp experiments the inward
      current increased over a period of 5-15 min on addition of membrane-permeable
      cAMP in 66% of the attempts when the cell was held at 0 mV and pulsed to negative
      membrane potentials. The inward current was completely blocked by chloride
      channel blockers. Washout reversed the effect of cAMP. The inward current was not
      diminished by substitution of impermeable cations for Na in the bath and was
      insensitive to TEA (tetraethylammoniumchloride). It is concluded that the inward
      current is mainly a chloride current. Cystic fibrosis transmembrane regulator
      (CFTR) could not be demonstrated in the NCL-SG3 cells. It is therefore possible
      that the chloride efflux is mediated by other types of chloride channels.

PMID- 8735653
TI  - Effects of the spin trap-alpha-phenyl-N-tert-butyl nitrone (PBN) in transient
      forebrain ischaemia in the rat.
AB  - The free radical spin trap alpha-phenyl-N-tert-butyl nitrone (PBN) has previously
      been shown markedly to reduce infarct size in permanent or transient focal
      ischaemia in rats. The mechanisms of action have not been clearly defined, but
      data obtained in focal ischaemia suggest microvessels or mitochondria as targets.
      Since microvascular dysfunction and/or mitochondrial failure are probably not the
      immediate causes of delayed neuronal damage following forebrain ischaemia in
      rats, we induced 15 min of two-vessel occlusion ischaemia in anaesthetized rats,
      and assessed brain damage by histopathological techniques 7 days later. Animals
      were treated either before (30 min) or after ischaemia (30 min or 6 h) with PBN
      or its vehicle. Other animals received a more soluble PBN analogue (2'-sulfonyl
      PBN), and received the drug 30 min prior to 12 or 15 min of ischaemia. PBN
      reduced neuronal necrosis in the neocortex when given 30 min post-treatment, but
      not when given before or 6 h after ischaemia, and it failed to reduce damage to
      the CA 1 sector of the hippocampus, or the caudoputamen. The sulphonyl derivative
      of PBN failed to reduce damage in any region. The results provide important hints
      as to the action of PBN. It is tentatively concluded that the nitrones ameliorate
      either the microvascular dysfunction or the mitochondrial failure, which could be
      the crucial events leading to infarction in focal ischaemia, but that they have
      only a weak effect on the mechanisms that yield selective neuronal necrosis in
      transient ischaemia of brief duration.

PMID- 8735654
TI  - Endogenous opioid mechanisms in hypothalamic blood flow autoregulation during
      haemorrhagic hypotension and angiotensin-induced acute hypertension in cats.
AB  - The influence of naloxone-induced general opiate receptor blockade on
      hypothalamic blood flow autoregulation was investigated in anaesthetized,
      artificially ventilated, temperature controlled cats. In order to study the
      changes of the hypothalamic blood flow (H2-gas clearance technique) at the lower
      limit of autoregulation systemic arterial pressure was reduced in a stepwise
      manner to 100, 80, 60 and 40 mmHg, by haemorrhage. Autoregulatory mechanisms of
      the hypothalamic vessels remained effective and hypothalamic blood flow showed no
      significant reduction until the arterial pressure was reduced to 60 mmHg in the
      vehicle-treated control cats. General opiate receptor blockade by 1 mg kg-1 mL-1
      i.v. injected naloxone resulted in a significant reduction of the autoregulatory
      capacity of the hypothalamic vessels: the blood flow followed passively the
      arterial pressure fall already from 100 mmHg mean arterial pressure. The effect
      of opiate receptor blockade on the upper limit of the autoregulation was studied
      during acute arterial hypertension, induced by angiotensin-II infusion (25
      micrograms 0.1 mL-1 min-1 i.v.). Hypothalamic blood flow remained remarkably
      steady following angiotensin-II infusion in the saline-treated control animals.
      Naloxone pretreatment (1 mg kg-1 mL-1 i.v.), however, induced a significant
      downward shift of the upper limit of the autoregulation, and hypothalamic blood
      flow started to increase in the 125-145 mmHg arterial pressure range. The
      narrowing of the autoregulatory range following general opiate receptor blockade
      suggests an important role of endogenous opioid peptides in hypothalamic blood
      flow autoregulatory mechanisms both in hypotensive and in hypertensive
      conditions.

PMID- 8735655
TI  - Changes in muscle function in response to 10 days of lower limb unloading in
      humans.
AB  - Force-generating capacity and electromyographic (EMG) activity of the knee
      extensor muscles were studied before and after short-term (10 d) unilateral lower
      limb unloading and during 4 days of recovery. Ten healthy males used crutches to
      prevent one of their lower limbs from weight-bearing while maintaining joint
      mobility as well as daily ambulatory activities. Knee extensor torque and
      quadriceps rectified EMG during maximal voluntary isometric contraction (MVC) was
      measured repeatedly before and after the intervention. Also, EMG at a fixed
      submaximal level (100 Nm; 30-45% MVC) and maximal angular velocity (AVmax),
      during unresisted knee extension, were assessed. Maximum torque decreased (P <
      0.05) by 13 +/- 8% in response to unloading while maximum EMG activity did not
      change after unloading or during recovery (P = 0.35). Submaximum EMG increased (P
      < 0.05) by 25 +/- 16% after unloading. Maximum and submaximum torque/EMG ratio
      decreased (P < 0.05) after unloading. AVmax decreased (P < 0.05) by 9 +/- 8%
      after unloading. The post value, however, was not different from that of the
      weight-bearing limb. Torque, EMG and AVmax were recovered (P > 0.05) after 4 days
      of resumed weight-bearing. The pronounced decrease and the rapid recovery in
      maximum torque appears not to be attributed to a change in muscle mass alone.
      Because the findings of unchanged maximum EMG and increased EMG at a submaximal
      force level suggest no change in neural drive, we propose that unspecific tissue
      factors in part impair muscle function in response to short-term loss of weight
      bearing activity. Results also indicate that recovery in muscle function after
      short-term unloading seems to be completed in a time span shorter than the period
      of preceding inactivity.

PMID- 8735656
TI  - EMG-activity and muscular performance of lower leg during stretch-shortening
      cycle after cooling.
AB  - To test the effect of cooling on EMG-activity of muscles working as an agonist
      and antagonist in the lower leg, 12 men dressed in shorts and jogging shoes
      performed a drop-jump exercise after 60 min exposures to 27 degrees C and 10
      degrees C. Cooling decreased mean skin temperature 5.6 +/- 0.4 degrees C (mean +/
      SD, P < 0.001), whereas rectal temperature was unaffected. The muscle
      temperature measured from m. gastrocnemius medialis decreased 4.1 +/- 0.3 degrees
      C (P < 0.01) at the depth of 30 mm below skin surface. To find the optimal
      stretching velocity for potentiation of elastic energy, the drop-jump exercise
      was performed from six different bench heights (10, 20, 30, 40, 50, and 60 cm).
      The optimal velocity was not altered on account of cooling. In cooled subjects
      during the stretch phase of the drop jumps the EMG-activity of m. triceps surae
      complex (agonist) increased (P < 0.05-0.001) while the activity of m. tibialis
      anterior (antagonist) remained unchanged. After cooling during the shortening
      phase of the jumps the EMG-activity of m. triceps surae complex decreased (P <
      0.05-0.001), whereas the activity of m. tibialis anterior increased (P < 0.05
      0.001). In addition, after cooling the peak EMG-activity appeared on the average
      28 ms earlier, which shifted the peak activity from the shortening phase (at 27
      degrees C) to the stretch phase (at 10 degrees C). Cooling increased the mean
      duration of stretch and shortening phases by 28 +/- 3 ms (P < 0.001) and 23 +/- 2
      ms (P < 0.001), respectively. The average force production during the shortening
      phase was 26% less (P < 0.05) after cooling, which resulted in a decreased rise
      of body centre of gravity (P < 0.05-0.01). It is concluded that during a stretch
      shortening cycle cooling alters the EMG-activity of agonist and antagonist
      muscles on a contradictory manner and results in an earlier peak EMG-activity.
      Therefore, alterations in motor unit recruitment could be responsible for the
      prolonged muscle contraction and decreased force production on account of
      cooling.

PMID- 8735657
TI  - Ageing is associated with reduced basal and stimulated release of nitric oxide by
      the coronary endothelium.
AB  - The ageing process is known to be associated with biochemical and functional
      changes in the heart. In an attempt to determine whether the ability of the
      coronary endothelium to secrete nitric oxide (NO) both at rest and in response to
      pharmacological stimulation is age dependent, we studied four groups of rats of
      different ages (1, 5, 15 and 26 months, respectively). Basal release of NO by
      endothelium as assessed by response of coronary flow to L-monomethylarginine, an
      inhibitor of NO synthase, was higher in the younger age groups. Similarly, the
      response of coronary flow to 5-hydroxytryptamine, a selective probe of
      endothelial capacity to secrete NO, was diminished in the older animals. This was
      confirmed by direct measurement of NO by chemiluminescence in the coronary
      effluent. In contrast, the response to glyceryl trinitrate appeared to be
      unaltered by age. It is concluded that in rats, basal and stimulated release of
      nitric oxide by the coronary endothelium deteriorates with age.

PMID- 8735658
TI  - Vasoconstriction in active calf persists after discontinuation of combined
      exercise with high-intensity elbow flexion.
AB  - The present study aimed to determine whether vasoconstriction in active calf
      occurring during combined exercise diminished or persisted when added low- and
      high-intensity elbow flexion exercise ceased and single leg exercise continued.
      Six active women (mean age, 21.2 years) participated in this study. During 10-min
      plantar flexion exercise at 10% of maximum voluntary contraction (MVC), elbow
      flexion exercise at 10% MVC was added over the 3rd and 4th min. Calf blood flow
      did not change significantly upon superimposition and cessation of this elbow
      flexion exercise. However, when elbow flexion exercise at 50% MVC was added
      during the 7th and 8th min, calf blood flow above the resting value (2.23 +/-
      0.23 mL 100 mL-1 min-1) decreased significantly (P < 0.05) from 6.72 +/- 0.87
      (6th min) to 5.14 +/- 1.36 mL 100 mL-1 min-1 after 2 min of combined exercise and
      was accompanied by a similar change in the non-exercising calf blood flow value.
      The vascular conductance of the exercising calf decreased significantly (P <
      0.01) from 6.48 +/- 1.08 (6th min) to 3.11 +/- 1.27 mL 100 mL-1 min-1 mmHg-1 at
      the end of the 2nd min of combined plantar flexion exercise with elbow flexion
      exercise at 50% MVC. After elbow flexion exercise at 50% MVC was discontinued and
      plantar flexion exercise at 10% MVC alone was performed, the vascular conductance
      in the exercising calf remained significantly low for the next 2 min. These
      results indicate that the vasoconstriction induced by adding high-intensity arm
      exercise is persistent, suggesting a major contribution of metabo-receptor
      mediated vasoconstriction rather than central command- and mechano-receptor
      mediated vasoconstriction.

PMID- 8735659
TI  - Growth resistance-sized arteries in response to bladder hypertrophy in the rat:
      time-course, DNA-synthesis and LDH-isoform pattern.
AB  - Bladder growth was induced by partial urethral obstruction. Bladder hypertrophy
      was evident at 53 h after obstruction and continued over a 6 weeks period. Small
      bladder arteries were taken from fixed anatomical locations of the bladder
      circulation, mounted in a small vessel myograph and the optimal diameter for
      maximal isometric force development was determined (Lmax K+ = 125 mM
      stimulation). Bladder hypertrophy was associated with an enlarged Lmax from 53h
      onward (compared with sham-operated controls) and Lmax continued to increase
      until 10 days after urethral obstruction. Between 10 days and 6 weeks no further
      increase of the diameter was observed. Increased diameters in vitro were
      accompanied by a transiently increased [3H] Thymidine uptake in the small
      arteries which peaked at 53 h after obstruction but was still above background at
      10 days. At this time point, small arterial growth was associated with a
      significant relative increase in the M isoform of LDH as determined with agarose
      electrophoresis on tissue homogenates. Thus organ growth induced small vessel
      growth in the rat is characterized by a rapid onset, increased but transient DNA
      turnover and LDH-isoform changes. The latter mimic changes seen in other types of
      smooth muscle growth.

PMID- 8735660
TI  - Effect of nicotine infusion in humans on platelet aggregation and urinary
      excretion of a major thromboxane metabolite.
AB  - The objective of this study was to evaluate further a possible role of nicotine
      as a stimulator of platelet aggregability and platelet arachidonic acid
      metabolism in vivo. In six healthy, non-smoking males, platelet aggregability was
      assessed by filtragometry and impedance aggregometry before, during and after an
      intravenous infusion of nicotine at two different doses (0.25 and 0.5 microgram
      kg-1 min-1) for 30 min. The aggregatory response was also measured after the
      addition of nicotine at final concentrations ranging from 10(-11) mol L-1
      directly to the aggregating blood. The synthesis of thromboxane A2 (TxA2) in
      platelets was estimated by quantitating the urinary excretion of 2.3-dinor
      thromboxane B2 (Tx-M). Despite the plasma concentrations of nicotine, cotinine
      and catecholamines in the range of those occurring during acute cigarette
      exposure, the excretion of Tx-M (204 +/- 36 pg mg-1 creatinine) remained
      unaltered during nicotine infusion. Similarly, platelet aggregatory response to
      collagen was not influenced by nicotine when infused or added in vitro. However,
      an enhanced aggregability was detected by filtragometry during the infusion of
      nicotine at the higher dose employed. The results indicate that nicotine, infused
      at moderate doses, produces a weak platelet stimulation that is not accompanied
      by significant release of thromboxane A2, as monitored by urinary excretion of Tx
      M. Although a direct action of nicotine on platelets cannot be excluded, it
      appears more likely that the enhancement of platelet function is mediated by
      other, secondary mechanisms.

PMID- 8735661
TI  - The preference for warm drinking water induces hyperhydration in heat-stressed
      lactating goats.
AB  - The aim of this study was to determine whether lactating goats regulate their
      water intake when given a choice between warm (35 degrees C) and cold (15 degrees
      C) water. Six lactating goats were kept individually in pens. At 07.00 h one
      bucket was filled with warm water and another with cold water. Water consumption
      was measured at intervals until 18.00 h. Water temperature was not controlled at
      night. Two experiments were made, one at normal room temperature (18-19 degrees
      C) and the other at 39-40 degrees C from 10.45 to 17.00 h. At normal room
      temperature the goats drank 6.0 +/- 1.4 L of the warm water but only 1.7 +/- 1.3
      L of the cold water (P < 0.001). The total water consumption, including the
      following night, was 9.2 +/- 1.6 L. This differed from control days, when only
      cold water was available (5.9 +/- 0.4 L; P < 0.05). Neither the plasma Na
      concentration nor the osmolality changed, which indicate that the goats regulated
      their fluid balance. In the experiments involving heat stress the goats drank
      11.5 +/- 1.7 L of the warm water but only 2.0 +/- 1.0 L of the cold water (P <
      0.001). In total, including the following night, they drank 16.2 +/- 2.6 L (P <
      0.001 vs. control days). Goats drank repeatedly despite falling plasma Na and
      osmolality, proving that their thirst was not induced by water losses. Their
      abdomens became distended, indicating that water was stored in the reticulo-rumen
      and explaining why their body weights increased. The goats appeared distressed.
      It is concluded that goats prefer to drink warm water. Nevertheless, our results
      suggest that, if possible, warm drinking water should not be given to lactating
      goats under hot ambient conditions.

PMID- 8735662
TI  - Olfaction in bird dogs during hunting.
AB  - The ability to catch scent continuously while running, which may be an essential
      skill for many animals of prey, requires that ambient air flows inward through
      the nose also during expiration. In this study on bird dogs, the direction of air
      flow was detected by measuring the temperature in the air inside the nostril.
      While resting, nose ventilation was synchronous with lung ventilation. While
      searching for ground scent, the dog was sniffing at a frequency of up to 200 s-1,
      a strategy which may create turbulence in the nasal passages and thereby enhance
      transport of scent molecules to the receptors in the ethmoidal cavity. When the
      bird dog was searching for game while running with its head high against the
      wind, it maintained a continuous inward air stream through the nose for up to 40s
      spanning at least 30 respiratory cycles. We suggest that expiratory gas flowing
      at high velocity from the trachea to the mouth cavity creates a lower pressure
      than in the nose thus causing an inward air stream through the nose during
      expiration by a Bernoulli effect.

PMID- 8735663
TI  - Psychiatric disorders after traumatic brain injury.
AB  - Substantial psychological and neurobehavioural evidence is available to support
      the hypothesis that traumatic brain injury (TBI) is a risk factor for subsequent
      psychiatric disorders. However, studies utilizing established psychiatric
      diagnostic schemes to study these outcomes after TBI are scarce, and no studies
      have included an assessment of personality disorders in addition to the major
      psychiatric disorders. This study utilizes structured psychiatric interviews to
      measure the prevalence of DSM-III(R) disorders in a sample of 18 subjects derived
      from a TBI rehabilitation programme. Results revealed high rates for major
      depression, bipolar affective disorder, generalized anxiety disorder, borderline
      and avoidant personality disorders. Co-morbidity was also high. A preliminary
      study of postulated predictive factors revealed possible roles for sex and for
      initial severity of injury. The study supports the association between TBI and
      psychiatric disorder, and suggests the need for monitoring, for prevention, and
      for treatment of psychiatric disorders after TBI.

PMID- 8735664
TI  - Assessment of pragmatic communication skills in adolescents after traumatic brain
      injury.
AB  - Deficits in pragmatic communication ability have a significant impact on
      functional outcome from traumatic brain injury (TBI), particularly during
      adolescence, when sophisticated social communication skills are developing. There
      are few published tests designed to assess pragmatic skills in this age group. In
      the present study, four tasks designed to tap various aspects of pragmatic
      communication ability were administered to three brain-injured adolescents and 36
      of their uninjured peers aged 15-18 years. The tasks evaluated the ability to
      negotiate, hint, describe a simple procedure, and understand sarcasm. The four
      tasks were found to tap distinct aspects of pragmatic ability in control
      subjects. Further, within the control group, task performance was related more to
      non-verbal reasoning ability than vocabulary skills. Scores for two of the three
      TBI subjects were poorer than those of their peers, while a third mildly injured
      subject performed within normal limits. Pragmatic task scores were consistent
      with the results of neuropsychological testing in the three TBI subjects.
      Implications for clinical management and recommendations for future research are
      discussed.

PMID- 8735665
TI  - Longitudinal profile of early motor recovery following severe traumatic brain
      injury.
AB  - A prospective longitudinal design was employed to describe early (first 6 weeks
      post-injury) motor function recovery in 16 individuals with severe traumatic
      brain injury (TBI). Reliable, standardized testing and scoring protocols were
      used by a physical therapist to evaluate subjects on several different aspects of
      motor function, including primitive reflexes, equilibrium/protective reactions,
      and a wide range of motor skills. The findings revealed that subjects
      demonstrated significant changes (chi 2, p < or = 0.05) between 1 and 6 weeks for
      the following variables: equilibrium reactions in sitting, rolling prone to side
      lying, sitting (supported and unsupported), kneeling, standing (assisted and
      independently), walking (assisted and independently), stair climbing with the use
      of the handrail and walking 25 m on even ground. A significant change in ability
      to sit supported between 1 and 3 weeks post-injury was also observed. In
      addition, recovery was found to be a heterogeneous process, in that different
      patterns of recovery were evident for the 26 variables and among individual
      subjects. The clinical implications for physical therapists involved in the
      rehabilitation of adults with a severe TBI are discussed.

PMID- 8735666
TI  - Screening of health risk factors prior to exercise or a fitness evaluation of
      adults with traumatic brain injury: a consensus by rehabilitation professionals.
AB  - A modified Delphi technique was used to obtain group consensus among 31
      rehabilitation professionals (RPs) from nine rehabilitation centres throughout
      the province of Quebec (Canada) to ascertain their expert opinion on the health
      risk factors (HRF) to be verified prior to beginning an exercise programme or
      evaluation for patients with traumatic brain injury (TBI). From the initial
      survey 87 items were generated, which were later regrouped into 27 HRFs. The
      relative importance of each HRF in regard to being screened before exercise in a
      population with TBI was then assessed by each RP using a five-point ordinal scale
      (1 = not important to 5 = extremely important). HRFs that were considered
      extremely important by at least 50% of HPs include: angina pectoris, aortic
      stenosis, exertional syncope, musculoskeletal sequelae which are exacerbated by
      exercise, outward aggressivity, pulmonary embolism, uncontrolled epilepsy
      (seizures), and ventricular arrhythmias. Professionals involved in exercising
      patients with TBI may find these factors useful to the efficient conduct of their
      rehabilitation programme.

PMID- 8735667
TI  - Chronic elemental mercury intoxication: neuropsychological follow-up case study.
AB  - In initial and follow-up investigations of neuropsychological function in a
      patient with elemental mercury intoxication, his scores were compared with those
      of a group of normal control subjects matched for sex, age and education. Each
      subject received a comprehensive neuropsychological examination including a
      personality inventory. On the initial examination the results indicated that the
      patient had a significant depression of performance intellectual functioning,
      impairments of attention, non-verbal short-term memory and visual judgement of
      angles and directions, psychomotor retardation and personality changes including
      depression, anxiety, desire to be alone, lack of interest and sensitivity to
      physical problems. Such an impairment picture is compatible with the previous
      observations of individuals with chronic exposure to elemental, organic or
      inorganic mercury. The follow-up study was undertaken about 1.5 years later. The
      results show that the patient's cognitive and personality functions were fully
      recovered. Our findings thus suggest a reversibility of impaired
      neuropsychological function in persons with elemental mercury poisoning if a
      prompt removal from the toxic environment is accomplished, together with proper
      medical treatment.

PMID- 8735668
TI  - Microvascular leakage in mouse pial venules induced by bradykinin.
AB  - The actions of bradykinin on pial venule leaky site formation were measured intra
      vitally in two inbred strains of mice (BALB/c and SJL/J). Pial venules were
      visualized using an open cranial window microscopy technique and the
      microvascular leaky site formation was assessed visually using a fluorescein
      dextran (70 kDa) INDICATOR. The SJL/J strain was found to be very sensitive to
      bradykinin-induced microvascular leakage. Pial venule leaky site formation was
      observed after exposure to 10 pM of bradykinin. In contrast, the BALB/c strain
      was found to be refractory to bradykinin-induced leakage. Pial arterioles were
      dilated in response to bradykinin in both strains of mice. These results support
      the concept that genetically controlled differences in vascular sensitivity and
      localization of inflammatory peptides play important roles in the generation of
      vasogenic oedema and inflammation in CNS trauma and disease.

PMID- 8735669
TI  - Specific eating and sleeping problems in Prader-Willi and Williams-Beuren
      syndrome.
AB  - Eating and sleeping problems have a high prevalence in mental retardation in
      general, but are also discussed as characteristic in some genetically determined
      disorders. A comparative analysis of eating and sleeping behaviours in 28 Prader
      Willi- and 32 Williams-Beuren syndrome children by psychometric instruments
      confirms excessive food-seeking behaviours in PWS and selective food refusal in
      WBS as specific problems. In both syndromes, however, there is considerable
      individual variability in these symptoms.

PMID- 8735670
TI  - Anthropometric and motor characteristics of Senegalese children with different
      nutritional histories.
AB  - The effects of Protein Energy Malnutrition (PEM) on the motor performance of 4.5
      6.5-year-old Senegalese children were studied. Body dimensions included weight,
      lengths, circumferences, and four skinfolds. Motor performance tests included a 3
      min endurance run, 4 x 10 m shuttle-run, distance throw, standing long jump and
      grip strength. The sample consisted of 147 children: 52 children who were
      hospitalized for severe undernutrition (severe UN group) during infancy but who
      had been nutritionally rehabilitated; 63 children who were never severely
      malnourished but who were chronically exposed to mild-to-moderate undernutrition
      up to the time of study (chronic UN group); and 32 well nourished children (well
      nourished group) from well-off households. After adjusting for sex and age, the
      well nourished group performed better than the severe UN and chronic UN groups.
      Principal components analysis resulted in two factors which explained 65% of the
      variance in anthropometry and motor performance. One was related to body size and
      the second to body composition. The three nutritional groups differed
      significantly in principal component scores for the two factors; chronic UN and
      severe UN children also differed for the second factor. Body composition,
      especially low fat mass appeared to be an important feature for motor performance
      in chronically undernourished children.

PMID- 8735671
TI  - Management of minor ailments in primary schoolchildren in rural and urban areas.
AB  - The concept of self-management in healthcare includes disease prevention, self
      diagnosis, self-treatment and appropriate consultation with health care
      practitioners. Within the context of childrens' ailments the decision-maker will
      usually be a carer. The aim of this study was to examine carers' management of
      minor childhood ailments within urban and rural settings. The subjects were
      primary schoolchildren (4-12 years of age) and the respondents were their parents
      or carers. Data were gathered using a pre-piloted structured questionnaire. The
      questionnaires were distributed through and collected by the head teachers of the
      13 participating schools. Of the 491 questionnaires distributed, 306 (62%) were
      returned and suitable for analysis. In total, 96 (31%) children had experienced a
      minor ailment in the preceding 2 weeks; the most commonly reported were cold,
      headache and gastrointestinal disturbance. Ninety-five respondents indicated how
      they managed this episode; the most common response was to treat the child with a
      medicine which they already had in the house (41%). A further 24 obtained a
      medicine specifically to manage the episode; 12 on prescription and 12 purchased
      an over-the-counter (OTC) medicine. The majority of respondents (86%) felt that
      they based their management decision on their own experience, only 10 felt their
      action was influenced by the advice of a pharmacist or doctor. Fifty children
      (16%) were reported to have a chronic illness. Several respondents volunteered
      comments suggesting that they would be cautious in their use of OTC medicines.
      This study indicates that in the majority of cases, carers manage children's
      minor ailments without recourse to professional advice.

PMID- 8735672
TI  - The impact of asthma in an inner city general practice.
AB  - This study was undertaken to find out the problems which children with asthma
      experience at school and at home. Patient interviews with 32 asthmatic children
      aged between 6 and 16 years using a semi-structured questionnaire were carried
      out in an inner city practice in Bristol. Twenty-three (71.8%) children
      experienced exercise-induced bronchospasm which particularly upset them at
      school. Eleven of 14 (78.5%) secondary schoolchildren said not being able to
      participate in sport was the worst thing about having asthma. Children seemed to
      accept that their inability to participate in sport was normal. Fourteen primary
      schoolchildren (77.7%) had restricted access to their inhalers. Primary
      schoolchildren were upset most by coughing or wheezing. Of 21 children who said
      smoke made their asthma worse, 18 lived in households where someone smoked.
      Children were more distressed by how their asthma affected them at school than at
      home. Thirty-one (96.8%) of the children viewed their asthma negatively, although
      26 (81.2%) felt they were in control of their asthma. School age children may
      have undiagnosed, exercise-induced bronchospasm causing considerable physical and
      psychological morbidity and are therefore being inadequately treated. Children's
      negative views of their asthma may be missed by conventional questioning and
      asthma clinics should ensure that children are encouraged to reveal the issues
      that concern them. Children should have easy access to their medication at
      school. Locally agreed management of asthma in schools may improve morbidity from
      asthma.

PMID- 8735673
TI  - Needs and responses of parents following the diagnosis of childhood cancer.
AB  - The diagnosis of childhood cancer can have wide-ranging effects on the family.
      The study investigated parents' views of the effects on family life at 6 months
      post-diagnosis, their satisfaction with services, and the support they needed and
      obtained. Ninety-eight families took part in the study which involved interviews
      with the main carer and self-report questionnaires completed by mothers and
      fathers. Levels of parental psychological distress were assessed, using the
      Malaise Inventory: 55% of mothers and 41% of fathers scored above the cut-off
      point held to indicate high levels of emotional distress. Relationships between
      scores on this measure and reported effects and support were investigated.
      Negative effects on parental employment, finance and family relationships and
      lack of emotional support were associated with higher levels of distress.
      Parental concerns regarding delay in diagnosis and unmet needs for counselling
      were noted.

PMID- 8735674
TI  - Summer holiday respite provision for the families of children and young people
      with learning disabilities.
AB  - While the provision of respite care is a relatively recent development in the
      provision of services to families, it is an area of considerable growth and
      apparent importance. Most service development and research has focused on the
      provision of residential or family-based respite care though some studies have
      commented on the apparent demand for other kinds of relief. This study describes
      a pilot summer playscheme for children with learning disabilities and the
      reactions of mothers to its provision. The characteristics of families who used
      the scheme are described and their felt needs for additional respite care
      explored. Mothers found the scheme very useful and expressed felt needs for
      substantially more such provision both during the summer and at other times. The
      findings are discussed in the context of the importance of developing respite
      services which meet the varied needs of families.

PMID- 8735675
TI  - Rebuilding confidence in oral contraceptives: a new imperative in family
      planning.
AB  - On December 14, 1995, the first public presentation of results of the
      Transnational Case-Control Study of Oral Contraceptives and the Health of Young
      Women was made at the winter meeting of the British Pharmacological Society at
      Brighton. Four weeks later, those results and further analyses were published in
      the British Medical Journal. There has been much debate about them in Europe and
      elsewhere. I feel privileged to have been invited to write a Leading Article
      about the safety of combined oral contraceptives in the British Journal of
      Clinical Pharmacology. These are personal opinions about the meaning of all the
      recent pharmacoepidemiological findings. With an historical context as the
      background I have added my personal reflections as a scientist and a public
      health doctor. These views do not necessarily reflect the views of my co
      investigators.

PMID- 8735676
TI  - A new opportunity for training in clinical pharmacology.

PMID- 8735677
TI  - Warfarin and aspirin as thromboprophylaxis in atrial fibrillation.
AB  - 1. Anticoagulant therapy with warfarin is now established as effective
      thromboprophylaxis against stroke in atrial fibrillation, in high-risk persons.
      Aspirin is indicated in moderate-risk persons or if warfarin is contraindicated.
      2. Risk stratification is suggested, using clinical factors supplemented by
      echocardiography, to aid choice of prophylaxis. 3. Further studies are required
      to establish how best to identify undiagnosed patients who have atrial
      fibrillation; to develop new therapeutic strategies; and to refine risk
      stratification to define which patients with atrial fibrillation are at the
      highest risk of stroke.

PMID- 8735678
TI  - A comparison of the effects of fluvastatin and bezafibrate on exercise
      metabolism: a placebo-controlled study in healthy normolipidaemic subjects.
AB  - 1. We have examined the interaction between aerobic exercise and lipid-lowering
      drugs in a crossover study of 16 healthy normolipidaemic volunteers who each
      received 21 days' treatment with bezafibrate (400 mg), fluvastatin (40 mg), and
      placebo, in random order. 2. Fluvastatin treatment reduced pre-exercise total
      cholesterol (TC) by 23% (P < 0.0001), low-density lipoprotein cholesterol (LDL-C)
      by 33% (P < 0.0001), and plasma triglycerides by 11%, compared with pre-treatment
      values. Bezafibrate reduced TC by 11% (P < 0.01); LDL-C by 9%; and plasma
      triglycerides by 40% (P < 0.01), compared with pre-treatment values. 3. During
      exercise, in comparison with placebo, and fluvastatin treatment, respectively,
      bezafibrate significantly reduced mean fat oxidation: 31% vs 39%, P = 0.035, 31%
      vs 39%, P = 0.002, plasma free fatty acid (FFA) availability, e.g. after 90 min
      of exercise: (t90) 520 vs 662 mumol 1(-1), P = 0.054, 520 vs 725 mumol 1(-1), P =
      0.016, and plasma levels of glycerol (t90): 59 vs 74 mumol 1(-1), P = 0.037, 59
      vs 73 mumol 1(-1), P = 0.016. Fluvastatin had no impact on fat metabolism in
      comparison with placebo. 4. Reduced plasma FFA concentration and lower fat
      oxidation during prolonged exercise on bezafibrate treatment may be due to an
      inhibition of hepatic acetyl coenzyme A carboxylase, resulting in reduced FFA
      release from adipose tissue. 5. The possibility that impaired fat metabolism on
      fibrates could induce premature fatigue during exercise of moderate duration and
      intensity should be examined in hyperlipidaemic patients.

PMID- 8735679
TI  - Efficacy and pharmacokinetics of a new intrarectal quinine formulation in
      children with Plasmodium falciparum malaria.
AB  - 1. Three groups of seven children aged 2-14 years with acute uncomplicated
      Plasmodium falciparum malaria received 12.8 mg kg-1 quinine gluconate by the
      intrarectal route (new cream formulation) or 8 mg kg-1 Quinimax (a Cinchona
      alkaloid alkaloid combination) by the intramuscular or intravenous (4 h infusion)
      route every 8 h for 3 days. Clinical and parasitological status was similar in
      the three groups at enrolment. 2. At 36 h, body temperature of all children of
      the three groups was returned to normal and remained so until day 7. 3. The
      decrease in parasitaemia did not differ between the three groups and the time
      required for a 50% fall in parasitaemia relative to baseline was 12.3 +/- 5.4,
      18.2 +/- 6.1 and 14.5 +/- 4.2 h in the intrarectal, intramuscular and intravenous
      treatment groups, respectively. Parasitaemia expressed as a percentage of initial
      values was not significantly different in the three groups after 48 h of
      treatment (7.4 +/- 16.0, 4.1 +/- 4.2 and 2.2 +/- 3.8% in the intrarectal,
      intramuscular and intravenous treatment groups, respectively). All the patients
      were aparasitaemic by day 7. 4. The tolerability of the three treatments was
      good; in particular, no rectal irritation was reported with the cream
      formulation. 5. The tmax occurred later after intrarectal (4.1 +/- 2.4 h) and
      intravenous infusion (3.8 +/- 0.5 h) than after intramuscular injection (1.6 +/-
      1.3 h) (P = 0.02). Cmax was lower with the intrarectal (3.0 +/- 1.0 mg 1(-1)) and
      intramuscular routes (3.2 +/- 0.7 mg 1(-1)) than with the intravenous route (5.1
      +/- 1.4 mg 1(-1)) (P = 0.003). Areas under the curve (AUC(0, 8 h)) were smaller
      with intrarectal (17.0 +/- 7 mg 1(-1) h) and intramuscular routes (19.4 +/- 4.8
      mg 1(-1)) than with the intravenous route (27.8 +/- 8.2 mg 1(-1) h) (P = 0.02).
      The approximate bioavailability of intrarectal quinine from 0 to 8 h was 36% vs
      intravenous quinine and 51% vs intramuscular quinine. 6. The good tolerability
      and efficacy of this new intrarectal quinine formulation outweigh its low
      approximate bioavailability. This new approach might thus be a safe and effective
      alternative to intramuscular quinine injection for the treatment of children with
      acute uncomplicated Plasmodium falciparum malaria in the field.

PMID- 8735680
TI  - Pharmacokinetics of butorphanol nasal spray in patients with renal impairment.
AB  - 1. The pharmacokinetics of butorphanol were evaluated in 18 female volunteers
      with varying degrees of renal function following a single, 1 mg transnasal dose
      of butorphanol tartrate. The creatinine clearance (CLCR) values for subjects in
      the normal (NOR), moderately impaired (MI), and severely impaired (SI) groups
      were > or = 70 ml min-1, 30-60 ml min-1, and < or = 30 ml min-1, respectively. 2.
      Serial blood and urine samples were collected immediately after dosing for 48 h.
      Plasma concentrations of butorphanol were determined using a specific
      radioimmunoassay. Urine concentrations of butorphanol and its metabolites
      (hydroxy-butorphanol, norbutorphanol and their glucuronide conjugates) were
      determined using h.p.l.c. with fluorescence detection. 3. There was no
      significant difference between the three treatments for peak plasma concentration
      of butorphanol and time to peak. Statistically significant differences were
      detected among the study groups for AUC, t1/2, MRT, and CLR with the mean values
      for severely impaired subjects significantly different from those of normal renal
      subjects; mean values for moderately impaired subjects were not significantly
      different from either the normal or severely impaired groups for all respective
      parameters. 4. The elimination half-life of butorphanol increased from 5.75 h in
      NOR to 10.48 h in SI. A similar trend was observed for MRT. Creatinine clearance
      (CLCR) significantly correlated with CLR (r = 0.563, P = 0.019), CLT/F (r =
      0.505, P = 0.033), t1/2 (r = -0.554, P = 0.017) and lambda (r = 0.606, P =
      0.008). 5. Although the exposure of butorphanol was greater in subjects with
      renal impairment, there was no trend for an increase in the number of adverse
      experiences reported by subjects with renal dysfunction. 6. Patients with less
      than 30 ml min-1 creatinine clearance may require less frequent administration of
      transnasal butorphanol as compared with subjects with normal or moderately
      impaired renal function.

PMID- 8735681
TI  - The antiemetic efficacy of tropisetron plus dexamethasone as compared with
      conventional metoclopramide-dexamethasone combination in Orientals receiving
      cisplatin chemotherapy: a randomized crossover trial.
AB  - 1. We report a single-blind randomized crossover trial comparing the efficacy of
      tropisetron plus dexamethasone (TROPDEX) vs conventional combination of
      metoclopramide, dexamethasone and diphenhydramine (METDEX) in prevention of acute
      and delayed vomiting in Chinese patients receiving high dose cisplatin. 2. Thirty
      six consecutive patients with nasopharyngeal carcinoma were entered into the
      study, all received cisplatin at a dose range of 60-100 mg/m2. Patients were
      randomized in the sequence of antiemetic regimens used in two consecutive cycles.
      3. The TROPDEX regimen consisting of tropisetron 5 mg i.v. and dexamethasone 20
      mg i.v. given on day 1 of chemotherapy, followed by oral maintenance with
      tropisetron 5 mg daily and dexamethasone 4 mg twice daily from day 2 to 6. The
      METDEX regimen consisting of metoclopramide 1 mg kg-1 i.v., dexamethasone 20 mg
      i.v. and diphenhydramine 25 mg i.v. given before chemotherapy and then 2 hourly
      for two more doses on day 1, followed by oral metoclopramide 20 mg 6 hourly from
      day 2 to 6. 4. Complete control of acute vomiting was observed in 64% of patients
      with TROPDEX as compared with 14% with METDEX (P < 0.01). While complete plus
      major control of acute vomiting was observed in 84% with TROPDEX as compared with
      58% with METDEX. The mean vomiting episodes on day 1 were 1.4 with TROPDEX as
      compared with 3.5 with METDEX (P < 0.01). There was, however, no significant
      difference between the two regimens in the control of delayed vomiting. 5. When
      patients randomized to TROPDEX in the second cycle were compared with those with
      TROPDEX in the first cycle, the antiemetic efficacy was reduced, with mean acute
      vomiting episodes of 2 in the former compared with 0.8 in the latter (P < 0.01).
      6. The most common adverse effect observed was headache in TROPDEX (27%) and
      dizziness in METDEX (40%). 7. In conclusion, the antiemetic regimen TROPDEX is
      effective in Chinese patients receiving high dose cisplatin chemotherapy and is
      well tolerated. It is better than conventional METDEX regimen in the control of
      acute vomiting, but not in the control of delayed vomiting.

PMID- 8735682
TI  - Haemodynamic effects of molsidomine and propranolol in patients with cirrhosis.
AB  - Propranolol and molsidomine have both been shown to decrease the hepatic venous
      pressure gradient in patients with cirrhosis. The present study aimed at
      assessing the effects of the combination of these two drugs on splanchnic and
      systemic haemodynamics of cirrhotic patients. Fifteen patients with biopsy proven
      alcoholic cirrhosis had haemodynamic measurements under basal conditions, 60 min
      after oral administration of 4 mg molsidomine then 15 min after intravenous
      administration of 15 mg propranolol. As compared with baseline values,
      molsidomine was found to decrease mean arterial pressure (-7.9%, (P < 0.01),
      cardiac output (-7.3%, P < 0.01), pulmonary wedged pressure (-45.8%, (P < 0.05)
      and hepatic venous pressure gradient (-11.7%, P < 0.01). Propranolol decreased
      heart rate (-21%, P < 0.01), further decreased cardiac output (-20.6%, (P < 0.01)
      and hepatic venous pressure gradient (-10.5%, P < 0.01). As a whole, molsidomine
      plus propranolol decreased mean arterial pressure (-8%, P < 0.01), heart rate (
      19%, P < 0.01), cardiac output (-26.5%, P < 0.01) and hepatic venous pressure
      gradient (-21%, P < 0.01). Pulmonary wedged pressure, liver blood flow and
      hepatic intrinsic clearance of indocyanine green were not significantly changed
      by the association of molsidomine and propranolol. We conclude that in patients
      with cirrhosis, molsidomine and propranolol potentiate their effects on hepatic
      venous pressure gradient. Such a combination could therefore prove useful in the
      treatment of portal hypertension.

PMID- 8735683
TI  - Effects of exogenous female sex-steroid hormones on lymphocyte beta 2
      adrenoceptors in normal females.
AB  - We have previously shown that lymphocyte beta 2-adrenoceptors (AR) are under
      cyclical control of sex-steroid hormones with greater receptor density during the
      luteal phase of the menstrual cycle. It has also been postulated that abnormal
      cyclical regulation of beta 2-AR might be a possible mechanism for premenstrual
      asthma. The effects of exogenous female sex-steroid hormones on lymphocyte beta 2
      AR function were studied in eight normal healthy females. They were evaluated at
      two successive menstrual cycles, during the follicular phase (day 1-6). They were
      randomized to receive single oral doses of either ethinyloestradiol 50 micrograms
      or medroxyprogesterone 10 mg in a cross-over study. Lymphocyte beta 2-AR
      parameters were evaluated at baseline (t0), 24 h (t24) and 72 h (t72) after
      ingestion. Baseline levels of progesterone and oestradiol were comparable on both
      cycles. Receptor density (Bmax) increased significantly (P < 0.01) from t0 after
      progesterone but not oestradiol at t 4: a 1.39-fold geometric mean difference
      (95% CI 0.96-2.00) between t24 vs t0. Receptor affinity (kd) and maximal cAMP
      response to isoprenaline (Emax) were not altered by either treatment. These
      results show that exogenous progesterone but not oestradiol, given during the
      follicular phase, significantly increased beta 2-AR. This, therefore, suggests
      that endogenous progesterone is probably responsible for previously observed
      increase in Bmax during the luteal phase of the female menstrual cycle. These
      findings may suggest possible therapeutic strategies for modulation of beta 2-AR
      in premenstrual asthma.

PMID- 8735684
TI  - Effect of food on the comparative pharmacokinetics of modified-release morphine
      tablet formulations: Oramorph SR and MST Continus.
AB  - The relative bioavailability and pharmacokinetic profiles of Oramorph SR (OSR)
      and MST Continus (MST), were evaluated by a randomized, four-way cross-over study
      in 24 healthy, male volunteers given single oral (30 mg) doses whilst fasting or
      after a high-fat breakfast. Mean Cmax, tmax, AUC (0,24h), AUC and tlag were
      significantly greater in fed compared with fasting subjects. Overall relative
      bioavailability of the two formulations (log AUC), was within the acceptable 80
      125% limits for bioequivalence both fed and fasting. Mean fasting Cmax for OSR
      was greater than MST (P < 0.05) but there was no difference between formulations
      in mean fed Cmax. No statistically significant difference between OSR and MST was
      found for other parameters nor in the incidence of adverse events. These results
      suggest that OSR and MST are bioequivalent and that if patients were to transfer
      between formulations, dosage adjustment would be unnecessary, irrespective of
      their meal schedules or food intake.

PMID- 8735685
TI  - Inhibition of caffeine metabolism by 5-methoxypsoralen in patients with
      psoriasis.
AB  - Eight patients with psoriasis were given 200 mg caffeine orally with or without
      1.2 mg kg-1 of 5-methoxypsoralen. Blood and urine samples were collected over a 2
      day period. During 5-methoxypsoralen coadministration, the apparent volume of
      distribution of caffeine remained unchanged, but oral clearance (CLp.o.)
      decreased from 9.5 +/- 3.8 (mean +/- s.d.) to 3.2 +/- 0.51 h-1 (P < 0.01). The
      area under the plasma concentration-time curve (AUC) increased from 24 +/- 9 to
      73 +/- 29 mg 1(-1) h (P < 0.001). This decrease in CLp.o. with increased AUC was
      consistent with a CYP1A2-dependent inhibition of caffeine N-demethylation which
      was further supported by significant decreases in the (AFMU+1U+1X)/17U and
      (AFMU+1U+1X)/17X urinary metabolic ratios.

PMID- 8735686
TI  - Analysis of the dihydropyrimidine dehydrogenase polymorphism in a British
      population.
AB  - Subjects with low or absent dihydropyrimidine dehydrogenase activity (DPD) are at
      risk of excessive toxicity or death when undergoing fluoropyrimidine
      chemotherapy. The DPD polymorphism has not been well characterized in the general
      population and the frequency of the enzyme deficiency is not known. In
      preparation for a population multicentre analysis of DPD activity, a comparison
      of sample preparation methods and a pilot study in normal volunteer subjects was
      performed. The stability of peripheral blood mononuclear cell DPD activity at -70
      degrees C was determined in 35 mM sodium phosphate buffer with 10% glycerol, 100%
      fetal calf serum (FCS) or as a dry pellet. DPD activity declined in FCS and
      increased in glycerol buffer, both reaching a plateau value 14 days after blood
      sampling. The glycerol buffer method was then used to study DPD activity in 50
      British subjects (36 M: 14F; 20-56 years). A 8.4-fold range in DPD activity was
      observed (30.4-256 pmol min-1 mg-1 protein). DPD activity was not influenced by
      age or cigarette smoking. This information will facilitate analysis of the DPD
      polymorphism in populations from different countries and ethnic groups.

PMID- 8735688
TI  - Interethnic variability in nifedipine disposition: reduced systemic plasma
      clearance in Mexican subjects.

PMID- 8735687
TI  - Debrisoquine 4-hydroxylation and sulphamethazine N-acetylation in patients with
      schizophrenia and major depression.
AB  - Debrisoquine 4-hydroxylation and sulphamethazine N-acetylation phenotypes were
      determined in 115 Czech drug-free in-patients with schizophrenia (n = 64) or
      major depressive disorder (n = 51). These data were compared with a control group
      of 321 healthy volunteers from the North-East German area of Greifswald. The
      distribution of debrisoquine hydroxylator phenotypes was almost identical in
      patients and healthy controls. Thus, there were 8.7% (95% CI 5.4-12.0%) of poor
      metabolizers (PM) among patients while 8.7% (95% CI 23.6-13.8%) PM among the
      control group. The prevalences of PM amongst patients with chronic schizophrenia
      and major depression were 10.9% (95% CI 4.5-21.3%) and 5.9% (95% CI 1.24-16.3%),
      respectively (chi 2 schizophrenics vs control = 0.315, NS; chi 2 depressive
      patients vs control = 0.450, NS). However, within the group of EM patients there
      was a significant (P < 0.01) shift towards higher debrisoquine metabolic ratios,
      reflecting a lower hydroxylation capacity in EM patients compared with EM healthy
      controls. The proportion of slow acetylators (SA) was 60.0% (95% CI 51.0-68.9%)
      in the entire group of psychiatric patients and 57.5% (95% CI 52.1-62.9%) in the
      control group (chi 2 all patients vs control = 0.195, NS). Furthermore, there
      were no significant differences in the prevalence of the SA phenotype between
      controls and schizophrenics or patients with major depression. Although the
      results of this modest study were negative, the presence of subtle differences in
      the metabolic capacity between psychiatric patients and a healthy population
      cannot be ruled out.

PMID- 8735689
TI  - Attitudes to adverse drug reaction reporting.

PMID- 8735690
TI  - Asynchronous transmitter release: control of exocytosis and endocytosis at the
      salamander rod synapse.
AB  - 1. We have studied exocytosis and endocytosis in the synaptic terminal of
      salamander rods using a combination of Ca2+ imaging, capacitance measurement and
      the photolysis of Ca2+ buffers. 2. The average cytoplasmic Ca2+ concentration at
      the dark resting potential was 2-4 microM. 3. An average cytoplasmic Ca2+
      concentration of 2-4 microM maintained a high rate of continuous exocytosis and
      endocytosis. 4. Changes in the rate of exocytosis were followed in less than 0.7
      s by compensatory changes in the rate of endocytosis. 5. Vesicle cycling in the
      rod synapse is specialized for graded transmission and differs from that
      previously described for synapses that release synchronized bursts of
      transmitter.

PMID- 8735691
TI  - In vivo synchronous membrane potential oscillations in mouse pancreatic beta
      cells: lack of co-ordination between islets.
AB  - 1. The properties of the oscillations in electrical activity of different beta
      cells within the same islet of Langerhans, and of different islets within the
      same pancreas, recorded in vivo, are described. 2. Simultaneous recordings of two
      cells within the same islet showed that the oscillations were synchronous. A
      rapid increase in blood glucose led to the simultaneous appearance of a
      transitory phase of continuous electrical activity in both cells. These results
      indicate that under physiological conditions, the islets operate as a functional
      syncytium. 3. Simultaneous recordings of cells from two different islets within
      the same pancreas showed that the oscillations in the electrical activity were
      not synchronous, which suggests that each islet is a functionally independent
      unit. Rapid changes in blood glucose led to the appearance of a transitory phase
      of increased electrical activity in both islets, although of different duration.
      These results suggest that the endocrine pancreas lacks a pacemaker driving the
      electrical activity of all the islets. 4. The comparison of the degree of
      activation of different islets, simultaneously recorded at different glucose
      concentrations, indicated that all the islets had a similar sensitivity to
      glucose. Furthermore, when the glucose concentration was increased, the
      electrical activity in both islets increased in parallel, suggesting that the
      amount of insulin released due to the increase in glycaemia was produced by the
      simultaneous response of all the islets and not by the recruitment of islets with
      different sensitivities to glucose. 5. Our results predict that the synchronous
      electrical activity of all the cells within an islet will result in widespread
      intracellular calcium oscillations and pulsatile insulin secretion. The
      periodicity of the pulses of insulin secretion in different islets is suggested
      to be of slightly different length and asynchronous.

PMID- 8735692
TI  - Effect on the fura-2 transient of rapidly blocking the Ca2+ channel in
      electrically stimulated rabbit heart cells.
AB  - 1. We used a rapid solution switcher technique to investigate mechanisms that
      might trigger intracellular Ca2+ release in rabbit ventricular myocytes. The
      study was carried out at 36 degrees C, intracellular Ca2+ (Ca2+i) was monitored
      with fura-2, and myocytes were electrically stimulated. 2. In patch-clamped
      cells, using the switcher to apply 20 microM nifedipine (an L-type Ca2+ current
      (ICa,L) blocker) 4 s before a depolarization to +10 mV reduced the amplitude of
      ICa,L to 10.25 +/- 2.25% of control (mean +/- S.E.M., n = 7 cells). 3. In
      externally stimulated cells, a rapid switch to 20 microM nifedipine 4 s before a
      stimulus reduced the amplitude of the fura-2 transient to 64.01 +/- 2.09% of
      control (mean +/- S.E.M., n = 19 cells). Using an in vivo calibration curve for
      fura-2, this was equivalent to a reduction in the Ca2+ transient to 50% during
      nifedipine application. Since an identical nifedipine switch reduced ICa,L to
      10.25%, it would seem that blocking a large fraction of ICa,L inhibited only half
      the Ca2+ transient. 4. The Na(+)-Ca2+ exchanger is inhibited by 5 mM nickel.
      Switching to 20 microM nifedipine +5 mM nickel 4 s before a stimulus abolished
      the fura-2 transient completely, consistent with the hypothesis that Ca2+ entry
      via reverse Na(+)-Ca2+ exchange might trigger a fraction of the fura-2 transient
      that remained during nifedipine. 5. After the Na(+)-K+ pump was inhibited by
      strophanthidin to increase intracellular Na+ (Na+i), a switch to 20 microM
      nifedipine became progressively less effective in reducing the fura-2 transient.
      This suggests that as Na+i rose, other mechanisms (perhaps reverse Na(+)-Ca2+
      exchange) appeared able to substitute for ICa,L in triggering the Ca2+ transient.
      6. In cells depleted of Nai+ to inhibit the triggering of sarcoplasmic reticulum
      (SR) Ca2+ release by reverse Na(+)-Ca2+ exchange, a nifedipine switch reduced the
      fura-2 transient to 10.9 +/- 4.19% (mean +/- S.E.M., n = 7; equivalent to 6.5% of
      the Ca2+ transient). 7. A switch to Na(+)-free (Li+) solution 100 ms before an
      electrical stimulus caused an increase in the fura-2 transient of 12.2 +/- 1.5%
      (mean +/- S.E.M., n = 7; equivalent to a 22% increase in the Ca2+ transient). 8.
      The results confirm that ICa,L is an important trigger for SR Ca2+ release and
      the resulting Ca2+ transient. However, since 50% of the Ca2+ transient remained
      when ICa,L was largely inhibited, it would seem likely that other SR trigger
      mechanisms might exist in addition. These data are consistent with the idea that
      Ca2+ entry via reverse Na(+)-Ca2+ exchange during the upstroke of the normal
      cardiac action potential might trigger a fraction of SR Ca2+ release and the
      resulting Ca2+ transient.

PMID- 8735693
TI  - Plateau-generating neurones in the dorsal horn in an in vitro preparation of the
      turtle spinal cord.
AB  - 1. In transverse slices of the spinal cord of the turtle, intracellular
      recordings were used to characterize and analyse the responses to injected
      current and activation of primary afferents in dorsal horn neurones. 2. A
      subpopulation of neurones, with cell bodies located laterally in the deep dorsal
      horn and dendrites radiating towards the pial surface, was distinguished by the
      ability to generate plateau potentials. Activation of the plateau potential by a
      suprathreshold depolarizing current pulse produced an increasing firing frequency
      during the first few seconds and a sustained after-discharge. 3. The plateau
      potential was assumed to be mediated by L-type Ca2+ channels since it was blocked
      by Co2+ (3 mM) and nifedipine (10 microM) and enhanced by Bay K 8644 (0.5-2
      microM). 4. The threshold for activating the plateau potential declined during
      the first few seconds of depolarization. The decline in threshold gradually
      subsided over 3-10 s after repolarization. 5. Frequency potentiation of the
      plateau potential contributed to wind-up of the response to depolarizing current
      pulses and primary afferent stimuli repeated at frequencies higher than 0.1-0.3
      Hz. 6. The sustained after-discharge mediated by the plateau potential was
      curtailed by a slow after-hyperpolarization (sAHP) evoked by strong
      depolarizations. The relative strength of the plateau potential and sAHP varied
      among cells. In some cells the plateau potential and sAHP interacted to produce
      damped oscillations upon depolarization. The sAHP was mediated by both apamin and
      tetraethylammonium (TEA)-sensitive K+ channels. 7. Our findings suggest that
      basic properties of sensory integration may reside with the specialized intrinsic
      response properties of particular subtypes of neurones in the dorsal horn.

PMID- 8735694
TI  - Burst-generating neurones in the dorsal horn in an in vitro preparation of the
      turtle spinal cord.
AB  - 1. In transverse slices of the spinal cord of the turtle, intracellular
      recordings were used to characterize and analyse the responses to injected
      current and activation of primary afferents in dorsal horn neurones. 2. A
      subpopulation of neurones, with cell bodies located centrally in the dorsal horn,
      was distinguished by the ability to generate a burst response following a
      hyperpolarization from rest or during a depolarization from a hyperpolarized
      holding potential. The burst response was inactivated at the resting membrane
      potential. 3. The burst response was mediated by a low threshold Ca2+ spike
      assumed to be mediated by T-type Ca2+ channels since it resisted tetrodotoxin and
      was blocked by 3 mM Co2+ or 100-300 microM Ni2+ and resembled the low threshold
      spike (LTS) described elsewhere. 4. Some burst-generating cells also displayed
      plateau potentials mediated by L-type Ca2+ channels. In these cells the burst
      following a hyperpolarizing current pulse, applied from the resting membrane
      potential, facilitated the activation of the plateau potential. Wind-up of the
      plateau potential was produced when the hyperpolarizing pulse generating the
      burst was repeated at 0.1-0.3 Hz or faster. 5. The burst response and the
      underlying low threshold Ca2+ spike were activated synaptically by primary
      afferent stimuli in a voltage range hyperpolarized from the resting membrane
      potential. 6. Cells with bursts were morphologically distinguishable from cells
      with bursts and plateau properties. 7. Our findings in this and the preceding
      paper show that the intrinsic response properties of particular subtypes of
      neurones in the dorsal horn have a profound influence on the amplitude and time
      course of the responses mediated by primary afferent fibres. We predict that
      these postsynaptic properties are probable targets for synaptic modulation.

PMID- 8735695
TI  - Effect of arachidonic acid on the L-type calcium current in frog cardiac
      myocytes.
AB  - 1. External application of the unsaturated fatty acid arachidonic acid (AA) to
      frog ventricular cells caused a large inhibition (approximately 85%) of the L
      type calcium current (ICa,L) previously stimulated by the beta-adrenergic agonist
      isoprenaline (Iso). The concentration producing half-maximal inhibition (K1/2)
      was 1.52 microM. The inhibitory effect did not affect the peak current-voltage
      relationship but produced a negative shift in the inactivation curve. 2. The
      inhibitory effect of AA also occurred in cells internally perfused with cAMP and
      non-hydrolysable analogues of cAMP. These data suggest that AA is acting by a
      mechanism located beyond adenylyl cyclase and does not involve changes in
      intracellular cAMP levels. 3. AA also inhibited the calcium current stimulated by
      internal perfusion with the catalytic subunit of protein kinase A (PKA),
      suggesting that AA acts downstream of channel phosphorylation. 4. The inhibitory
      effect of AA on the isoprenaline- or cAMP-stimulated ICa,L is largely reduced in
      cells internally perfused with the thiophosphate donor analogue of ATP, ATP gamma
      S, or protein phosphatase 1 and 2A inhibitors like microcystin (MC) or okadaic
      acid (OA). External application of the phosphatase inhibitor calyculin (Caly)
      also reduced the AA effect. These data suggested that the AA effect on ICa,L
      involves activation of protein phosphatase activity. 5. The effect of AA on ICa,L
      was not affected by staurosporine, an inhibitor of protein kinases. It was also
      unaffected in cells internally perfused with GTP gamma S. These results suggest
      that neither a PKC- nor a G-protein-mediated mechanism are likely to be involved
      in the effect of AA on ICa,L. 6. A saturated fatty acid, myristic acid (MA), had
      no inhibitory effect on the isoprenaline-stimulated Ca2+ current, whereas, in the
      same cells arachidonic acid produced approximately 85% inhibition of ICa,L. 7.
      The inhibitory effect of AA was not affected by exposing the cells to
      indomethacin (Indo), an inhibitor of the metabolism of AA by cyclo-oxygenase, nor
      nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase pathway.
      However, the non-metabolizable analogue of AA, 5,8,11,14-eicosatetraynoic acid
      (ETYA), was without effect on the isoprenaline-stimulated ICa,L. 8. These results
      suggest that AA inhibits ICa,L via a mechanism which involves, in part,
      stimulation of protein phosphatase activity. This process could provide a new
      mechanism in the modulation of calcium channel activity.

PMID- 8735696
TI  - Slow inactivation of Na+ current and slow cumulative spike adaptation in mouse
      and guinea-pig neocortical neurones in slices.
AB  - 1. Spike adaptation of neocortical pyramidal neurones was studied with sharp
      electrode recordings in slices of guinea-pig parietal cortex and whole-cell patch
      recordings of mouse somatosensory cortex. Repetitive intracellular stimulation
      with 1 s depolarizing pulses delivered at intervals of < 5 s caused slow,
      cumulative adaptation of spike firing, which was not associated with a change in
      resting conductance, and which persisted when Co2+ replaced Ca2+ in the bathing
      medium. 2. Development of slow cumulative adaptation was associated with a
      gradual decrease in maximal rates of rise of action potentials, a slowing in the
      post-spike depolarization towards threshold, and a positive shift in the
      threshold voltage for the next spike in the train; maximal spike repolarization
      rates and after-hyperpolarizations were unchanged. 3. The data suggested that
      slow adaptation reflects use-dependent removal of Na+ channels from the available
      pool by an inactivation process which is much slower than fast, Hodgkin-Huxley
      type inactivation. 4. We therefore studied the properties of Na+ channels in
      layer II-III mouse neocortical cells using the cell-attached configuration of the
      patch-in-slice technique. These had a slope conductance of 18 +/- 1 pS and an
      extrapolated reversal potential of 127 +/- 6 mV above resting potential (Vr)
      (mean +/- S.E.M.; n = 5). Vr was estimated at -72 +/- 3 mV (n = 8), based on the
      voltage dependence of the steady-state inactivation (h infinity) curve. 5. Slow
      inactivation (SI) of Na+ channels had a mono-exponential onset with tau on
      between 0.86 and 2.33 s (n = 3). Steady-state SI was half-maximal at -43.8 mV and
      had a slope of 14.4 mV (e-fold)-1. Recovery from a 2 s conditioning pulse was bi
      exponential and voltage dependent; the slow time constant ranged between 0.45 and
      2.5 s at voltages between-128 and -68 mV. 6. The experimentally determined
      parameters of SI were adequate to simulate slow cumulative adaptation of spike
      firing in a single-compartment computer model. 7. Persistent Na+ current, which
      was recorded in whole-cell configuration during slow voltage ramps (35 mV s-1),
      also underwent pronounced SI, which was apparent when the ramp was preceded by a
      prolonged depolarizing pulse.

PMID- 8735697
TI  - Mechanisms of manganese transport in rabbit erythroid cells.
AB  - 1. The mechanisms of manganese transport into erythroid cells were investigated
      using rabbit reticulocytes and mature erythrocytes and 54Mn-labelled MnCl2 and
      Mn2-transferrin. In some experiments iron uptake was also studied. 2. Three
      saturable manganese transport mechanisms were identified, two for Mn2+ (high and
      low affinity processes) and one for transferrin-bound manganese (Mn-Tf). 3. High
      affinity Mn2+ transport occurred in reticulocytes but not erythrocytes, was
      active only in low ionic strength media such as isotonic sucrose and had a Km of
      0.4 microM. It was inhibited by metabolic inhibitors and several metal ions. 4.
      Low affinity Mn2+ transport occurred in erythrocytes as well as in reticulocytes
      and had Km values of approximately 20 and 50 microM for the two types of cells,
      respectively. The rate of Mn2+ transport was maximal in isotonic KCl, RbCl or
      CsCl, and was inhibited by NaCl and by amiloride, valinomycin,
      diethylstilboestrol and other ion transport inhibitors. The direction of Mn2+
      transport was reversible, resulting in Mn2+ efflux from the cells. 5. The uptake
      of transferrin-bound manganese occurred only with reticulocytes and depended on
      receptor-mediated endocytosis of Mn-Tf. 6. The characteristics of the three
      saturable manganese transport mechanisms were similar to corresponding mechanisms
      of iron uptake by erythroid cells, suggesting that the two metals are transported
      by the same mechanisms. 7. It is proposed that high affinity manganese transport
      is a surface representation of the process responsible for the transport of
      manganese across the endosomal membrane after its release from transferrin. Low
      affinity transport probably occurs by the previously described Na(+)-Mg2+
      antiport, and may function in the regulation of intracellular manganese
      concentration by exporting manganese from the cells.

PMID- 8735698
TI  - A patch-clamp study of delayed rectifier currents in skeletal muscle of control
      and mdx mice.
AB  - 1. Potassium currents were measured in the extensor digitorum longus muscle of
      normal and mdx mice, which lack the protein dystrophin, using the cell-attached
      and inside-out patch clamp techniques, in the presence of asymmetrical K+
      concentrations (3 mM in the pipette, 160 mM in the bath). 2. In cell-attached
      patches, the delayed rectifier was the most commonly found potassium channel,
      with a density of roughly 8 channels microns-2. Outward macroscopic currents were
      activated in macropatches depolarized to potentials positive to -60 mV. The
      probability of opening reached half-maximal values around -40 mV for control
      patches and -31 mV for patches from mdx mice. 3. Tail currents were linear in the
      range between -60 and +20 mV, reversing close to -100 mV. The single channel
      current at 0 mV, estimated from non-stationary analysis of variance, was used in
      conjunction with the slope of the linear part of the tail current to calculate
      the single channel conductance, yielding a value of 19 +/- 1 pS. 4. At 0 mV, the
      delayed rectifier inactivated with two time constants, of 70 +/- 20 ms and 600 +/
      200 ms. Prepulses of 500 ms duration to different potentials produced incomplete
      inactivation with inactivation reaching 50% of its maximum at -50 mV. 5. Single
      channel activity was recorded using small pipettes. Both single channel
      conductance and kinetic behaviour were in agreement with the macroscopic current
      data. 6. In excised patches, the delayed rectifier current ran down, unmasking
      other K+ channels. A Ca(2+)-dependent K+ channel of 186 pS (BK-like channel) was
      found frequently in patches bathed in solutions containing appropriate
      concentrations of calcium, especially at stronger depolarizations. A K+ channel
      of 63 pS was unmasked in control excised patches bathed in solutions devoid of
      ATP. This channel was not observed in patches excised from mdx fibers.

PMID- 8735699
TI  - Contribution of a non-inactivating potassium current to the resting membrane
      potential of fusion-competent human myoblasts.
AB  - 1. Using the patch-clamp technique, a new non-inactivating voltage-gated
      potassium current, IK(ni), was studied in cultured fusion-competent human
      myoblasts. 2. IK(ni) is activated at voltages above -50 mV and its conductance
      reaches its maximum around +50 mV. Once activated, the current remains at a
      steady level for minutes. 3. Reversal potential measurements at various
      extracellular potassium concentrations indicate that potassium ions are the major
      charge carriers of IK(ni). 4. IK(ni) is insensitive to potassium channel blockers
      such as charybdotoxin, dendrotoxins, mast cell degranulating (MCD) peptide, 4
      aminopyridine (4-AP), 3,4-diaminopyridine (3,4-DAP) and apamin, but can be
      blocked by high concentrations of TEA and by Ba2+. 5. A potassium channel of
      small conductance (8.4 pS at +40 mV) with potential dependence and
      pharmacological properties corresponding to those of IK(ni) in whole-cell
      recording is described. 6. IK(ni) participates in the control of the resting
      potential of fusion-competent myoblasts, suggesting that it may play a key role
      in the process of myoblast fusion.

PMID- 8735700
TI  - Competition between Mg2+ and spermine for a cloned IRK2 channel expressed in a
      human cell line.
AB  - 1. A cloned inwardly rectifying K+ channel, IRK2, was expressed in a human cell
      line, human embryonic kidney (HEK) 293T. Its electrophysiological properties were
      examined using the patch clamp technique in the whole-cell, cell-attached and
      inside-out patch configurations. 2. The cells transfected with IRK2 cDNA
      exhibited a K+ current which showed classical properties of inwardly rectifying
      K+ channels at both whole-cell and single-channel levels. 3. In the inside-out
      patch configuration, intracellular Mg2+ (Mg2+i blocked the outward currents in a
      voltage-dependent and virtually time-independent manner. Mg2+i (1-100 microM)
      caused a decrease in the unitary current amplitude of the IRK2 channel by
      inducing subconducting levels. 4. In the absence of Mg2+i, intracellular spermine
      blocked the outwardly flowing IRK2 currents in a voltage- and time-dependent
      manner. Spermine (1-100 nM) did not affect the unitary channel current amplitude
      but reduced the channel open probability. The spermine block showed a slower time
      and steeper voltage dependence than the Mg2+i++ block. 5. When both these
      blockers were present, Mg2+i apparently attenuated the inhibitory effect of
      spermine on the outwardly flowing IRK2 currents. This interaction was voltage and
      time dependent, and could be well explained by a model in which Mg2+i and
      spermine competitively bind to the channel with their individual first-order
      kinetics. This competition would induce time-dependent transits of the channel
      between the Mg2+i -and spermine-blocked states via a single open state, thereby
      preserving a certain size of persistent outward currents at depolarized
      potentials.

PMID- 8735701
TI  - Substance P hyperpolarizes vagal sensory neurones of the ferret.
AB  - 1. Intracellular recordings were made in intact and in acutely dissociated vagal
      afferent neurones (nodose ganglion cells) of the ferret to investigate the
      effects of substance P(SP). 2. In current-clamp recordings, SP (100 nM) applied
      by superfusion hyperpolarized the membrane potential (7 +/- 0.7 mV; mean +/-
      S.E.M.; n = 105) and decreased the input resistance in 80% of the neurones. With
      voltage-clamp recording, SP produced an outward current of 3 +/- 0.2 nA (n = 10).
      3. The SP current was concentration dependent with an estimated EC50 of 68 nM.
      The SP-induced hyperpolarization or current was mimicked by the tachykinin
      receptor NK1 agonist Ac-[Arg6, Sar9, Met(O2)11]SP(6-11) (ASM-SP; 100 nM; n = 10)
      and blocked by the NK1 antagonist CP-96,345 (10 nM; n = 6), but not by the NK2
      antagonist SR48968 (100 nM; n = 4). No measurable change in membrane potential or
      input resistance was observed with application of either [beta-Ala8]neurokinin A
      or senktide, selective NK2 and NK3 receptor agonists, respectively (100 nM; n = 3
      for each agonist). 4. The reversal potential (Erev) for the SP outward current
      was -85 +/- 2.5 mV (n = 4). The Erev for the SP response shifted in a Nernstian
      manner with changes in extracellular potassium concentration. Alterations in
      extracellular sodium or chloride concentrations had no significant effect on the
      Erev for the SP response (n = 3 for each ion). 5. Nominally Ca(2+)-free external
      solution abolished the SP response. Removal of magnesium from the extracellular
      solution had no effect on the response. 6. Caesium (100 microM), barium (1 mM),
      tetraethylammonium (TEA; 5 mM), apamin (10 nM) and 4-aminopyridine (4-AP; 4 mM)
      each completely prevented the SP response (n > or = 3 for each). 7. These results
      indicate that SP, via an NK1 receptor, can induce a Ca(2+)-dependent outward
      potassium current which hyperpolarizes the resting membrane potential of vagal
      afferent somata.

PMID- 8735702
TI  - Deactivation and desensitization of non-NMDA receptors in patches and the time
      course of EPSCs in rat cerebellar granule cells.
AB  - 1. Spontaneous and evoked non-NMDA receptor-mediated EPSCs were recorded from
      cerebellar granule cells in slices at approximately 24 and approximately 34
      degrees C. The EPSC decay was fitted with the sum of two exponential functions.
      2. The time courses of non-NMDA receptor deactivation and desensitization were
      determined with fast concentration jumps of glutamate onto patches from cultured
      granule cells. Deactivation (decay time constant tau = 0.6 ms at 24 degrees C)
      was substantially faster than desensitization (tau = 4 ms). Both processes were
      fitted by single exponential functions. 3. The decay of the fast component of the
      spontaneous EPSC (tau EPSCfast = 0.9 ms at 23 degrees C) was marginally slower
      than deactivation but too fast to be determined by desensitization. Our results
      suggest that the decay of this component is set by both the rate of decline of
      transmitter concentration and channel deactivation. 4. A simple diffusion model
      predicts that the time course of transmitter in the cleft declines slowly during
      the later stages of its action. The slow phase of transmitter removal could
      account for the time course of the slow component of the spontaneous EPSC (tau
      EPSCslow = 8 ms at 23 degrees C).

PMID- 8735703
TI  - Involvement of protein kinases in the upregulation of acetylcholine release at
      endplates of alpha-bungarotoxin-treated rats.
AB  - 1. ACh release from motor nerve endings in diaphragms of rats treated chronically
      with alpha-bungarotoxin (alpha-BuTX) is upregulated at the level of the
      individual endplate. Involvement of protein kinases in this mechanism of synaptic
      adaptation was investigated. 2. Miniature endplate potentials (MEPPs) and
      endplate potentials (EPPs) were recorded after mu-conotoxin treatment, which
      prevents muscle action potentials. The quantal content at endplates was
      calculated 'directly', i.e. by dividing the EPP amplitude by the MEPP amplitude.
      3. Incubation of muscles from control and alpha-BuTX-treated rats with H-7, a
      protein kinase C (PKC) inhibitor, reduced MEPP amplitudes but had no clear effect
      on quantal contents. Polymyxin B, another PKC inhibitor, had a similar effect on
      muscles from alpha-BuTX-treated rats. 4. Incubation of muscles from alpha-BuTX
      treated rats with K252a, a broad-spectrum protein kinase inhibitor of, amongst
      others, PKC, Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) and
      neurotrophin receptor tyrosine kinases, resulted in a 30% decrease of the quantal
      content. However, K252a did not change the quantal content of controls.
      Incubations with the closely related compound K252b, which has an exclusively
      extracellular action, had a similar effect. 5. KN62, a specific inhibitor of
      CaMKII, decreased the mean quantal content of muscles from alpha-BuTX-treated
      rats by 18%. 6. Tyrphostin 51, a selective tyrosine kinase inhibitor, had no
      effect on quantal contents of muscles from alpha-BuTX-treated and control rats.
      However, it increased the frequency and amplitude of MEPPs in muscles from alpha
      BuTX-treated rats, leaving those of controls unchanged. 7. The extent of
      reduction of quantal content, caused by K252a, K252b and KN62, varied between
      endplates of individual muscles from alpha-BuTX-treated rats; quantal contents at
      endplates with small MEPPs were more sensitive than those at endplates with large
      MEPPs. 8. It is concluded that PKC does not play a role in the mechanism of
      upregulation of ACh release at endplates of alpha-BuTX-treated rats. Instead,
      CaMKII and some tyrosine kinases in the presynaptic membrane, as well as in the
      cytoplasm, might be involved.

PMID- 8735704
TI  - Tensile strength and dilatational elasticity of giant sarcolemmal vesicles shed
      from rabbit muscle.
AB  - 1. Mechanical properties of the surface membrane of skeletal muscle were
      determined on sarcolemmal vesicles (mean diameter, 71 microns) shed by rabbit
      psoas muscle swelling in 140 mM KC1 containing collagenase. 2. Vesicles were
      stressed by partial aspiration into parallel bore pipettes. The isotropic
      membrane tension so created caused an increase in membrane area which expresses
      itself in an elongation of the vesicle projection into the pipette. 3. For
      individual vesicles, a linear relationship between membrane tension and membrane
      area increase was found up to the point when the vesicle burst, i.e. sarcolemmal
      vesicles behaved as perfectly elastic structures. 4. The maximum tension
      sarcolemmal vesicles could sustain before bursting was 12.4 +/- 0.2 mN m-1
      (median +/- 95% confidence interval), and the corresponding fractional increase
      in membrane area was 0.026 +/- 0.005 (median +/- 95% confidence interval). The
      elastic modulus of area expansion was 490 +/- 88 mN m-1 (mean +/- S.D.). 5. In
      conformity with cited comparable work on red blood cells and artificial lipid
      vesicles, the strength and area elasticity of the skeletal muscle membrane are
      considered properties of the fluid lipid matrix of the membrane and of the degree
      to which the bilayer is perturbed by lipid-protein interaction.

PMID- 8735705
TI  - Ca2+ loading reduces the tensile strength of sarcolemmal vesicles shed from
      rabbit muscle.
AB  - 1. Sarcolemmal vesicles shed by rabbit muscle were loaded with Ca2+ by means of
      A23187 or ionomycin. [Ca2+]0 was buffered between 0.8 and 20 microM. Membrane
      strength was measured by pipette aspiration. 2. At 20 microM Ca2+ many vesicles
      underwent autolysis, or were so weak that they burst instantly on aspiration.
      Between 10 and 2 microM Ca2+ a graded decrease in membrane strength was
      demonstrable. At 0.8 microM Ca2+ the mechanical properties of the sarcolemma
      remained unaltered. 3. Mg2+ carried by A23187 does not mimic the effect of Ca2+.
      The ionophore itself similarly did not cause a decrease in membrane tensile
      strength. 4. Pre-treatment with BAPTA-AM, so as to buffer internal Ca2+, partly
      protected vesicles against the decrease in membrane strength produced by Ca2+
      loading. 5. Membrane strength was not restored by adding excess BAPTA to the
      bathing solution, so as to reverse the Ca2+ gradient. An irreversible degradation
      of the membrane consequent upon raised [Ca2+]1 seems indicated. 6. These findings
      are discussed in relation to the mechanisms which have been advanced to account
      for the role of elevated [Ca2+]1 in cell death. 7. An attempt to use
      staphylococcal alpha-toxin as an alternative means to permeabilize the sarcolemma
      led to the incidental finding that this pore-forming protein itself greatly
      weakens the membrane in doses lower than required for effective permeabilization.

PMID- 8735706
TI  - Augmented force output in skeletal muscle fibres of Xenopus following a preceding
      bout of activity.
AB  - 1. The effect of a brief period of activity on subsequent isometric tetanic force
      production was investigated in single muscle fibres of Xenopus laevis. 2.
      Following a train of ten tetani separated by 4 s intervals, tetanic force was
      significantly augmented by about 10%. The tetanic force augmentation persisted
      for at least 15 min and then slowly subsided. A similar potentiation was seen
      following trains of five and twenty tetani. 3. During the period of tetanic force
      potentiation, tetanic calcium was reduced by more than 30%, and intracellular pH
      was reduced from 7.15 +/- 0.07 to 7.03 +/- 0.11 (n = 4). 4. Fibre swelling was
      greatest at 1 min and then subsided over 15-20 min and possibly accounted for a
      small part of the observed force potentiation. 5. A reduction in the inorganic
      phosphate (P1) concentration of more than 40% was found in fibres frozen in
      liquid nitrogen at the peak of force potentiation compared with resting fibres.
      6. It is concluded that the augmentation of tetanic force found after a brief
      preceding bout of activity is due to a reduction in inorganic phosphate. This
      mechanism may underlie the improved performance observed in athletes after warm
      up.

PMID- 8735707
TI  - Force responses following stepwise length changes of rat skeletal muscle fibre
      types.
AB  - 1. Force responses following stepwise length changes of Ca(2+)-activated skinned
      leg muscle fibres (6 degrees C) of the rat were correlated with their myosin
      heavy chain (HC) isoforms (myosin HC I, fibre type I; myosin HC IIA, type IIA;
      myosin HC IID (HC IIX), type IID (type IIX); myosin HC IIB, type IIB) in order to
      study the mechanical properties of these molecules. 2. Marked differences in the
      time behaviour of force transients following quick releases of fibre length
      existed between various muscle fibres, and a conspicuous correlation with their
      myosin HC complement was noticed (order of velocity: IIB > IID > IIA > > I). No
      differences were found in the relationship between the applied length step and
      the resulting force (T1, T2 curves). 3. Our results suggest that the heads of
      various myosin heavy chain isoforms exhibit different kinetic properties. The
      differences concern the kinetics of the myosin head movements and the duration of
      cyclic interactions between myosin heads and thin filaments. The extent of force
      generating movements and the mean elongation of attached heads in the isometric
      state seem to be independent of the isoform.

PMID- 8735708
TI  - Substance P contributes to rapidly adapting receptor responses to pulmonary
      venous congestion in rabbits.
AB  - 1. This study tested the hypothesis that substance P stimulates rapidly adapting
      receptors (RARs), contributes to the increase in RAR activity produced by mild
      pulmonary congestion, and evokes an augmented response from RARs when combined
      with near-threshold levels of pulmonary congestion. 2. RAR activity, peak
      tracheal pressure, arterial blood pressure and left atrial pressure were measured
      in paralysed, anaesthetized and ventilated rabbits. Substance P was given i.v. in
      one-half log incremental doses to a maximum of 3 micrograms kg-1. Mild pulmonary
      congestion was produced by inflating a balloon in the left atrium to increase
      left atrial pressure by 5 mmHg. Near-threshold levels of pulmonary congestion
      were produced by increasing left atrial pressure by 2 mmHg. 3. Substance P
      produced dose-dependent increases in RAR activity. The highest dose given
      increased the activity from 1.3 +/- 0.5 to 11.0 +/- 3.1 impulses bin-1. Increases
      in left atrial pressure of 5 mmHg increased RAR activity from 3.8 +/- 1.4 to 14.7
      +/- 3.9 impulses bin-1. Blockade of NK1 receptors with CP 96345 significantly
      attenuated RAR responses to substance P and to mild pulmonary congestion. 4.
      Doses of substance P, which alone had no effect, stimulated the RARs when
      delivered during near-threshold levels of pulmonary congestion. 5. The findings
      suggest that substance P augments the stimulatory effect of mild pulmonary
      congestion on RAR activity, most probably by enhancing hydraulically induced
      microvascular leak.

PMID- 8735709
TI  - Postnatal development of the nociceptive withdrawal reflexes in the rat: a
      behavioural and electromyographic study.
AB  - 1. The postnatal development of nociceptive withdrawal reflexes was studied. In
      awake intact rats, forelimb, hindlimb and tail reflexes were recorded on
      videotape. In decerebrate spinal rats, electromyography (EMG) was used to record
      nociceptive withdrawal reflexes in musculi extensor digitorum longus (EDL),
      peronei, gastrocnemius-soleus (G-S) and biceps posterior-semitendinosus (BP-ST).
      Thermal (short-lasting CO2 laser pulses) and mechanical stimulation were used. 2.
      In adults, nociceptive withdrawal reflexes were typically well directed and
      reflex pathways to single hindlimb muscles had functionally adapted receptive
      fields. By contrast, at postnatal day (P) 1-7, the nociceptive withdrawal
      reflexes were often inappropriate, sometimes producing movements towards the
      stimulation, and EMG recordings revealed unadapted variable receptive fields.
      With increasing age, the nociceptive withdrawal reflexes progressively became
      well directed, thus producing localized withdrawal. Both withdrawal movements and
      spatial organization of the receptive fields were adult-like at P20-25. 3. Up to
      P25, reflex thresholds were more or less constant in both intact awake rats and
      spinal decerebrate rats, except in G-S in which no nociceptive withdrawal
      reflexes were evoked from P20 on. After P25, mechanical, but not thermal,
      thresholds increased dramatically. 4. EMG recordings revealed that during the
      first three postnatal weeks, the latency of the CO2 laser-evoked nociceptive
      withdrawal reflexes decreased significantly in peronei and BP-ST, but not in EDL,
      and thereafter increased significantly in peronei, BP-ST and EDL. The magnitude
      of the nociceptive withdrawal reflexes in these muscles increased markedly
      between P7 and P20 and showed little change thereafter. 5. Possible mechanisms
      underlying the postnatal tuning of the nociceptive withdrawal reflexes are
      discussed.

PMID- 8735710
TI  - Cutaneous inhibitory receptive fields of withdrawal reflexes in the decerebrate
      spinal rat.
AB  - 1. The inhibitory cutaneous input to the withdrawal reflex pathways to single
      hindlimb muscles was investigated in decerebrate spinal rats (n = 53) using
      electromyography. 2. Withdrawal reflexes in the peronei, extensor digitorum
      longus and tibialis anterior muscles of the leg were strongly inhibited by
      conditioning mechanical, thermal (CO2 laser) and intracutaneous electrical
      stimulation of specific skin areas. By contrast, withdrawal reflexes in the
      biceps posterior-semitendinosus muscles of the thigh could only be weakly
      inhibited by conditioning skin stimulation. 3. Powerful inhibition of withdrawal
      reflexes in single lower leg muscles was elicited from the ipsilateral hindpaw
      plantar area, which would move towards the stimulation on contraction in the
      respective muscle. In addition, weak nociceptive inhibition was evoked from the
      corresponding skin areas on the contralateral hindlimb and, in some muscles, the
      tail. 4. The ipsilateral inhibitory and excitatory receptive fields of the
      withdrawal reflexes in single muscles overlapped somewhat. On stimulation of
      these transitional areas the reflex responses were preceded by a short-lasting
      inhibition. 5. Graded mechanical and thermal stimulation demonstrated prominent
      inhibitors effects from nociceptive receptors. Weak inhibitory effects were
      elicited by innocuous mechanical stimulation, suggesting a weak contribution from
      low threshold mechanoreceptors. Latency measurements indicated an inhibitory
      input from both myelinated and unmyelinated fibres. 6. In conclusion, the
      withdrawal reflex pathways receive a powerful nociceptive inhibitory input
      through spinal pathways. The movement-related organization of this input suggests
      that it serves to prevent inappropriate withdrawal reflexes.

PMID- 8735711
TI  - Changes in muscle strength, relaxation rate and fatiguability during the human
      menstrual cycle.
AB  - 1. The effect of the different phases of the menstrual cycle on skeletal muscle
      strength, contractile properties and fatiguability was investigated in ten young,
      healthy females. Results were compared with a similar group on the combined (non
      phasic) oral contraceptive pill (OC). Cycle phases were divided into the early
      and mid-follicular, mid-cycle (ovulatory) and mid- and late luteal. Cycle phases
      were estimated from the first day of the menstrual bleed. 2. Subjects were
      studied weekly through two complete cycles. Measurements included quadriceps and
      handgrip maximum voluntary isometric force and the relaxation times, force
      frequency relationship and fatigue index of the quadriceps during percutaneous
      stimulation at a range of frequencies from 1 to 100 Hz. 3. In the women not
      taking the OC there was a significant increase of about 11% in quadriceps and
      handgrip strength at mid-cycle compared with both the follicular and luteal
      phases. Accompanying the increases in strength there was a significant slowing of
      relaxation and increase in fatiguability at mid-cycle. No changes in any
      parameter were found in the women taking the OC. 4. The changes in muscle
      function at mid-cycle may be due to the increase in oestrogen that occurs prior
      to ovulation.

PMID- 8735712
TI  - Ontogeny of postural adjustments during sitting in infancy: variation, selection
      and modulation.
AB  - 1. The aim of the study was to find out whether the development of postural
      adjustments occurs via a coupling of simple muscle responses, such as stretch
      reflexes, or via selection from an innate repertoire of centrally generated
      response patterns. 2. Postural responses during sitting on a moveable platform
      were assessed in eleven healthy infants at 5-6, 7-8 and 9-10 months of age.
      Multiple surface EMGs and kinematics were recorded while the infants were exposed
      to slow and fast horizontal forward (Fw) and backward (Bw) displacements of the
      platform. 3. From the youngest testing age onwards, largely variable but
      direction-specific muscle activation patterns were present. Fw translations
      resulted predominantly in an activation of the neck flexor, the rectus abdominis
      and rectus femoris muscle, while the neck-, thoracal- and lumbar extensor muscles
      (NE, TE, LE) and the hamstrings (Ham) showed varying amounts of inhibition.
      During Bw translations NE, TE, LE and Ham were preferably activated. The muscle
      activity could not be explained by simple stretch reflex mechanisms, but is
      likely to reflect centrally generated motor activity maturing in a predetermined
      way. However, indications for a contribution of stretch reflex mechanisms were
      also present. 4. With increasing age the variation in muscle activation patterns
      decreased, resulting in a selection of the most complete patterns. The ability to
      modulate the amplitude of the selected, most complete patterns during Fw
      translations, with respect to platform velocity and initial pelvis position,
      emerged at 9-10 months.

PMID- 8735713
TI  - Training affects the development of postural adjustments in sitting infants.
AB  - 1. The present study addressed the question of whether daily balance training can
      affect the development of postural adjustments in sitting infants. 2. Postural
      responses during sitting on a moveable platform were assessed in twenty healthy
      infants at 5-6, 7-8 and 9-10 months of age. Multiple surface EMGs and kinematics
      were recorded while the infants were exposed to slow and fast horizontal forward
      (Fw) and backward (Bw) displacements of the platform. After the first session the
      parents of nine infants trained their child's sitting balance daily. 3. At the
      youngest age, when none of the infants could sit independently, the muscle
      activation patterns were direction specific and showed a large variation. This
      variation decreased with increasing age, resulting in selection of the most
      complete responses. Training facilitated response selection both during Fw and Bw
      translations. This suggests a training effect on the first level of the central
      pattern generator (CPG) model of postural control. 4. Training also affected the
      development of response modulation during Fw translations. It accelerated the
      development of: (1) the ability to modulate EMG amplitude with respect to
      platform velocity and initial sitting position, (2) antagonist activity and (3) a
      distal onset of the response. These findings point to a training effect on the
      second level of the CPG model of postural adjustments.

PMID- 8735714
TI  - Genetic pathways in colorectal cancer.
AB  - The model of colorectal tumorigenesis put forward by Fearon and Vogelstein has
      had great influence on molecular oncology. They proposed that a series of
      mutations occur in the progression from normal cells to colorectal cancer and
      that these mutations are associated with the histological features of such
      tumours. Several postulates of the model appear to be correct, particularly its
      emphasis on the stepwise accumulation of genetic changes and the inclusion of
      mutations at the adenomatous polyposis coli (APC) and TP53 loci. Since the
      publication of the original model, however, mutations at other loci have been
      identified which may be alternatives or additions. There is also evidence to
      suggest that some colorectal cancers develop along a different genetic pathway.
      In this review, we discuss how tumour development can occur as Darwinian
      evolution through selection of advantageous somatic mutations. The non-random
      nature of mutation selection gives rise to genetic pathways of tumorigenesis. In
      addition, we consider the Fearon and Vogelstein model, its shortcomings and
      possible additions to it. The evidence suggests that not all colorectal cancers
      follow the same genetic pathway during carcinogenesis.

PMID- 8735715
TI  - Malignant peripheral nerve sheath tumour with vascular differentiation: a report
      of four cases.
AB  - Four cases of malignant peripheral nerve sheath tumour showing vascular
      differentiation are described. One case was associated with neurofibromatosis 1
      and contained angiosarcomatous, cartilaginous and rhabdomyoblastic elements. The
      other cases occurred in patients without neurofibromatosis and showed a spectrum
      of vascular lesions ranging from lobulated, haemangioma-like structures to
      angiosarcoma. These are the first recorded examples of this phenomenon not
      associated with neurofibromatosis. Immunohistochemical examination demonstrated
      the endothelial nature of the lesions in all cases and revealed cells positive
      for alpha-smooth muscle actin, probably pericytes, closely apposed to the
      endothelium.

PMID- 8735716
TI  - Expression of blood group-related antigens in cholangiocarcinoma in relation to
      non-neoplastic bile ducts.
AB  - The abnormal expression of blood group related antigens has been reported in many
      malignant tumours; however, such expression in cholangiocarcinoma has not been
      examined systematically. The expression of blood group-related antigens (A, B, H,
      Lewis(a), Lewis(b), Lewis(x), Lewis(y), carbohydrate antigen 19-9 and
      carcinoembryonic antigen) was investigated immunohistochemically in 75 cases of
      cholangiocarcinoma (31 peripheral type and 44 hilar type). In non-neoplastic bile
      ducts, A, B, and H antigens were expressed in large bile ducts, while
      Lewis(a,b,y) and carbohydrate antigen 19-9 were variably expressed in both large
      and small bile ducts. Lewis(x) and carcinoembryonic antigen was not found in non
      neoplastic bile ducts. In cholangiocarcinomas, A, B, and H, antigens were more
      frequent in the hilar type than in the peripheral type, although the difference
      was not significant. The expression of the blood-group related antigens,
      particularly A, Lewis(a,b,y), carcinoembryonic antigen, and carbohydrate antigen
      19-9, was frequent in the tumour cells in well differentiated adenocarcinomas,
      while their immunoreactivity was less frequent in poorly differentiated
      adenocarcinomas. The superanuclear and luminal expression of these antigens in
      carcinoma cells was frequent in well differentiated adenocarcinomas, and the
      diffuse, cell membranous and stromal expression of these antigens was relatively
      frequent in poorly differentiated adenocarcinomas and adenosquamous carcinoma.
      The A, B, and H immunoreactivity of both non-neoplastic bile ducts and
      cholangiocarcinomas was consistent with the host blood group type. These findings
      suggest that both the expression and intracellular distribution of blood group
      related antigens in cholangiocarcinoma are related to the differentiation of
      cholangiocarcinoma and, possibly, to the parent structure.

PMID- 8735717
TI  - Diagnostic accuracy of stereotactic core biopsy in a mammographic breast cancer
      screening programme.
AB  - Stereotactic core biopsy was performed on 200 women for 206 mammographically
      suspicious non-palpable lesions detected over a period of 2 years as part of the
      Australian national programme for early detection of breast cancer. This study
      aimed to assess the reliability of stereotactic core biopsy in this context and
      to develop a protocol for the evaluation of stereotactic core biopsy in
      mammographically detected non-palpable breast lesions. Fifty-one of 52 malignant
      lesions found by stereotactic core biopsy were confirmed by excision biopsy (one
      women declined excision). Nine (4.5%) women had atypical ductal hyperplasia on
      stereotactic core biopsy; at excision, six were low grade carcinomas (in situ or
      invasive carcinomas), one was a 3 mm focus of grade 3 invasive duct carcinoma,
      one was atypical ductal hyperplasia, and one patient refused excision biopsy. In
      29 (14.5%) women the histology of the stereotactic core biopsy was considered not
      to correlate with the radiological abnormality, and excision biopsy was advised:
      in four of these women carcinomas were found. One hundred and ten (55%) women had
      116 benign lesions on stereotactic core biopsy: on follow-up, one of these
      patients has been found to have a carcinoma. Core biopsy number and sequence were
      analysed demonstrating that no particular biopsy was more diagnostic than any
      other, and that the diagnostic yield of three cores was statistically equal to
      that of five cores. The procedure was well-tolerated and there were few
      complications. Thus, stereotactic core biopsy is an accurate and safe method for
      diagnosis of mammographically detected non-palpable breast lesions, and we
      believe it is the diagnostic technique of choice in breast cancer screening
      programmes. However, a stereotactic core biopsy diagnosis of atypical ductal
      hyperplasia requires excision biopsy since a diagnosis of low grade intraduct
      carcinoma cannot be excluded. Furthermore, if tissue obtained by stereotactic
      core biopsy does not correlate with the mammographic abnormality, excision biopsy
      should be performed.

PMID- 8735718
TI  - Immunohistochemical evaluation of nm23-H1 gene product in transitional cell
      carcinoma of the bladder.
AB  - The expression of the nm23-H1 gene has been suggested to have an inverse
      association with metastases in certain tumours. The aim of this study was to
      investigate the relationship of nm23-H1 immunohistochemical expression with
      pathological tumour variables and survival in a series of transitional cell
      carcinomas (TCCs) of the bladder. Formalin-fixed, paraffin-embedded archival
      tissue from 87 carcinomas (Ta-T1 45 cases) and T2-T4 (42 cases) was immunostained
      (Strept ABC/HRP) with the NDPK-A monoclonal antibody (NDPK-A) against nm23-H1
      protein. The tumours had already been evaluated for immuno-expression of p53
      protein. In addition, DNA analysis was performed by flow cytometry. Results were
      analysed using the linear trend in proportions test, the Fisher's exact test and
      multivariate analysis. Paradoxically, advanced tumour stage showed significant
      correlation with nm23-H1 immunopositivity in muscle invasive TCCs (P(t) = 0.01).
      Patients with nm23-H1 positive, muscle invasive TCCs had a worse prognosis at a
      level of suggestive statistical significance (PF = 0.08). In multivariate
      analysis, using a Cox's proportional hazards survival model with six variables,
      tumour grade, disease stage and synchronous p53 and nm23-H1 detection showed
      significant correlation with poor patient survival (P = 0.014, P = 0.049 and P =
      0.05, respectively).

PMID- 8735719
TI  - MIB-1 expression and iododeoxyuridine labelling in soft tissue sarcomas: an
      immunohistochemical study including correlations with p53, bcl-2 and histological
      characteristics.
AB  - We investigated the relationship between immunohistochemical estimates of
      proliferative activity and expression of bcl-2 protein and mutant p53 protein in
      23 cases of soft tissue sarcoma. Furthermore, the reproducibility of estimates of
      proliferative activity was analysed and correlations between the variables and
      with mitotic score were investigated. Proliferative activity was assessed by use
      of monoclonal antibody MIB-1 and staining for iododeoxyuridine (IdUrd), and
      evaluated in multiple, random, systematically sampled fields of vision. MIB-1
      indices were higher than those of IdUrd but for each case the two values were
      positively correlated (r = 0.78). The MIB-1 index correlated positively with
      mitotic score (2P < 0.001) and malignancy grade (2P = 0.001). The intraobserver
      reproducibility of the MIB-1 and IdUrd indices were excellent (r = 0.98 and r =
      0.90, respectively). p53 expression was detected in 43% and strong bcl-2
      expression was present in 57% of the studied cases. Expression of p53 and bcl-2
      were not significantly correlated to proliferative activity or the histological
      features. We conclude, that the MIB-1 index is a reliable and reproducible
      estimate of proliferative activity and might improve the accuracy of conventional
      malignancy grading of soft tissue sarcomas. Furthermore, the results indicate
      that neither mutant p53 protein nor bcl-2 oncogene alone are sufficient to induce
      increased proliferation in these sarcomas.

PMID- 8735720
TI  - Comparison of cytomorphological and architectural heterogeneity in
      mammographically-detected ductal carcinoma in situ.
AB  - Many classification schemes have been proposed for ductal carcinoma in situ.
      Architectural heterogeneity is widely recognized. Cytonuclear grade appears to
      have greater prognostic significance than architectural pattern. This study
      assesses heterogeneity using a classification based on cytological grade and
      compares this to architectural heterogeneity in mammographically detected ductal
      carcinoma in situ. One hundred and twelve cases were classified according to
      architectural subtypes and the carcinoma nuclei were graded. Necrosis and
      microcalcification were assessed. Eighty-four percent of ductal carcinomas in
      situ had a single nuclear grade, whereas only 39% showed a single architectural
      pattern. High grade nuclei were present in 87% of cases. Necrosis was associated
      with high nuclear grade. In contrast to architectural heterogeneity, this study
      shows little ductal carcinoma in situ heterogeneity when classification is based
      on nuclear grade. Thus, a cytomorphological classification should have the
      advantage of consistency and reproducibility in comparison to architecture-based
      classification systems.

PMID- 8735721
TI  - Sclerosing epithelioid fibrosarcoma.
AB  - A case of sclerosing epithelioid fibrosarcoma arising in the thigh of a 40-year
      old man is reported. This recently described sarcoma has a distinctive
      histological appearance which may cause confusion with a variety of other
      sarcomas with an epithelioid pattern, and indeed with benign soft tissue tumours
      showing hyalinization. Despite its bland cytology, sclerosing epithelioid
      fibrosarcoma is capable of metastases, often several years after surgical
      removal. The patient described here developed lung metastases five years after
      excision and remains alive a further three years later. The differential
      diagnosis and possible histogenesis are discussed.

PMID- 8735722
TI  - Mixed tumour of the vagina.
AB  - A 33-year-old Japanese woman presented with a polypoid 2.5 x 2.5 x 1.9 cm mass
      located in the posterior wall of the lower vagina. Microscopically, the tumour
      was composed of benign epithelial and stromal-type elements. Predominant
      epithelial elements were mucinous glands with squamous metaplasia and islands of
      mature squamous epithelium. The stromal-type cells showed reticular or short
      fascicular patterns with a transition to the epithelial elements. There was no
      dual epithelial-myoepithelial combination in the glands as seen in so-called
      mixed tumours (pleomorphic adenomas) of the salivary gland.
      Immunohistochemically, the epithelial elements were strongly positive for
      cytokeratin, PKK1 and epithelial membrane antigen, while the stromal-type cells
      co-expressed PKK1 and vimentin. Staining for S-100 protein, muscle actin, alpha
      smooth muscle actin, desmin, and CD34 was uniformly negative in the tumour cells.
      The DNA pattern was diploid. The patient is alive and well without recurrence for
      50 months after excision. These results indicate that an epithelial cell
      proliferation, probably of the remnant vestibular gland, plays a major role in
      the development of mixed tumours of the vagina.

PMID- 8735723
TI  - Malignant solitary fibrous tumour of the peritoneum.

PMID- 8735724
TI  - Multilocular peritoneal inclusion cyst (multicystic mesothelioma) with hyaline
      globules.

PMID- 8735725
TI  - Granulomatous lymphadenitis associated with metastatic malignant melanoma.

PMID- 8735726
TI  - Hepatocellular carcinoma arising in an adenoma: value of QBend 10 immunostaining
      in diagnosis of liver cell carcinoma.

PMID- 8735727
TI  - Syringocystadenocarcinoma papilliferum.

PMID- 8735728
TI  - Cytokeratins and cytokeratin staining in diagnostic histopathology.

PMID- 8735729
TI  - Treatment of fibromas.
AB  - This study defines the current modes of treatment of patients with uterine
      fibromas with a review of the literature. Progesterone treatments appear to be
      principally used in cases of minor functional symptomatology and we discuss
      recent studies of mifepristone. GnRH agonists are particularly effective in
      preoperative treatment for conservative surgery. The indications and results of
      hysteroscopic resection and laparoscopic myomectomy are compared to those of
      classic myomectomy and hysterectomy. The indications for myolysis are discussed.

PMID- 8735730
TI  - Collagen and glycosaminoglycans of Wharton's jelly and their alterations in EPH
      gestosis.
AB  - Some prenatal pathological processes may be caused by biochemical and
      morphological alterations in the umbilical cord (UC). EPH-gestosis is the most
      common pregnancy-associated pathological process. For these reasons the role of
      collagen and glycos-aminoglycans (GAGs) of UC in pathobiochemistry of this
      syndrome seems to be important. We studied histology of extracellular matrix
      components, quantity, solubility and molecular polymorphism of collagen,
      proportional relationships between various types of collagen, the amounts of GAGs
      and proportional relationships between them in Wharton's jelly of control
      newborns delivered by healthy mothers and those delivered by mothers with EPH
      gestosis. We found that Wharton's jelly is abundant in collagen and GAGs. This
      collagen is very insoluble and resistant to the action of depolymerizing agents
      (4% EDTA-Na2, pepsin). Types I, III and V collagens were isolated and quantified.
      Hyaluronic acid constitutes about 70%, whereas sulphated GAGs constitute about
      30% of total GAGs. EPH-gestosis is accompanied by significant increase in
      sulphated GAGs: hyaluronic acid ratio. The EPH-gestosis-associated alterations in
      Wharton's jelly correspond to 'premature ageing' of this tissue.

PMID- 8735731
TI  - Varicella and pregnancy.
AB  - OBJECTIVE: To appreciate the risk of embryo-foetopathy in case of maternal
      varicella occurring before 20 weeks of gestation, as well as the maternal
      complication risk (notably pulmonary) in case of maternal varicella occurring the
      third trimester of pregnancy. METHOD: Over the period from January 1987 to
      February 1995, 20 patients were managed for maternal varicella confirmed during
      the pregnancy. From these observations, the authors, by studying the literature,
      attempt to better specify the real fetal and/or maternal complication risk in
      case of maternal varicella. RESULTS: In their personal series of 20 cases,
      including 17 before 20 weeks of gestation, the authors have noted no embryo
      foetopathy. Similarly, no maternal complication (notably pulmonary complication),
      has been found. Careful study of the literature allows to specify some points. In
      case of varicella before 20 weeks, one observes an identical frequency of
      spontaneous abortions, as compared to the general population and a moderated
      increase of the frequency of premature delivery. The risk of congenital varicella
      syndrome reaches about 1.3%. Finally the risk of neonatal varicella consists in a
      maternal infection which occurs during the perinatal period and which is source
      of a high perinatal morbidity. The prenatal diagnosis is based essentially and
      currently, on the amniocentesis with viral research by polymerase chain reaction
      (PCR) in the amniotic fluid, completed by a ultrasound supervision. CONCLUSION:
      The occurrence of maternal varicella during the pregnancy is rare (0.7/1000)
      because more than 90% of women are immunized. The risk of congenital varicella
      syndrome is limited to the 20 first weeks and seems very weak, authorizing
      therapists to reassure patients presenting a varicella during their pregnancy.
      Nevertheless, the risk of pulmonary complications for the mother, in case of
      varicella during the third trimester, does exist and requires appropriated
      treatment.

PMID- 8735732
TI  - Changes of erythrocyte microrheology during normal pregnancy and after delivery.
AB  - OBJECTIVES: The changes of blood hemorheology during pregnancy are still the
      subject of many studies. Erythrocyte membrane deformability (ED) as one of the
      main components forming blood hemorheology was studied in the present paper.
      STUDY DESIGN: The changes in ED were measured in healthy non-pregnant women and
      in three groups of pregnant women in the first, second and third trimester. The
      last group consisted of women after delivery. The colloid-osmotic hemolysis
      method in relation to the change ionic strength was used for ED measurements. The
      significance of differences was evaluated by the unpaired Student's t-test.
      RESULTS: The results revealed that ED during pregnancy progressively decreases
      but after delivery significantly increases. Statistical differences between means
      in all three trimesters were significant in comparison with non-pregnant women.
      CONCLUSION: We conclude that the changes of ED are important for the normal
      course of gravidity and are probably connected to hormonal changes during
      pregnancy and after delivery.

PMID- 8735733
TI  - Stretching of the cervix and stripping of the membranes at term: a randomised
      controlled study.
AB  - OBJECTIVE: To determine whether routine antepartum stretching of the cervix and
      stripping of the membranes at term would shorten the length of pregnancies, and
      whether this correlated with cervical status and fetal and maternal parameters.
      DESIGN: A prospective, randomised, controlled study of 293 term gravidas, free of
      medical complications, divided into two groups: stretching/stripping, and non
      stretching/stripping. Digital separation of the fetal membranes from the lower
      uterine segment, and cervical stretching, were performed during routine vaginal
      examination of the first group. In the second group, only routine vaginal
      examination was performed. RESULTS: Of 293 patients, 152 underwent a trial of
      stretching and stripping; 141 served as a control group. The mean interval (hours
      to delivery after the procedure) was 136 h (S.D. 10), compared to 161 h (S.D. 11)
      in the control group (P = 0.095; not significant), but with only a trend towards
      the shorter interval in the first group. When patients were matched according to
      weeks of gestation and fetal and maternal parameters, only those at 41 weeks'
      gestation or more had a significant reduction in the interval from the procedure
      to delivery (mean 91 h (S.D. 8) compared to mean 125 h (S.D. 10) in the control
      group; P < 0.007). This observation was independent of cervical status and other
      maternal or fetal parameters. CONCLUSIONS: Only patients > or = 41 weeks'
      gestation benefitted from stretching of the cervix and stripping of the fetal
      membranes. The effect was not dependent on the cervical status or other maternal
      and fetal parameters.

PMID- 8735734
TI  - The effect of surgical castration on lipid metabolism in premenopausal and
      postmenopausal women.
AB  - OBJECTIVE: To investigate the effect of endogenous estrogen on lipid and
      lipoprotein metabolism in premenopausal and postmenopausal women. DESIGN:
      Prospective randomized study. SETTING: Department of Obstetrics-Gynecology,
      Beilinson Medical Center and Tel-Aviv University Medical School, Israel.
      SUBJECTS: Twenty-seven women, 15 premenopausal and 12 postmenopausal, undergoing
      surgical castration (total abdominal hysterectomy and bilateral salpingo
      oophorectomy). METHOD: Blood samples were drawn before the surgical intervention
      and after a 6-month interval. MAIN OUTCOME MEASURES: Assays were performed for
      estradiol, luteinising hormone and follicle-stimulating hormone, and
      triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol and total
      cholesterol/HDL as well as HDL/LDL ratio. RESULTS: No significant differences
      were found in both groups, before castration and after 6 months. A modest, but
      statistically significant, rise in triglycerides was observed in the
      premenopausal group. CONCLUSIONS: The serum lipid and lipoprotein profile
      encountered in premenopausal and postmenopausal women were unchanged 6 months
      after surgical castration. The clinical significance indicates that the effect of
      endogenous estrogen on lipid metabolism is doubtful and should be further
      investigated.

PMID- 8735736
TI  - Epithelial ovarian carcinoma of low malignant potential.
AB  - OBJECTIVE: The aim of this study was to evaluate the interest of sonographic
      features, serum marker tumors and conservative treatment especially by
      laparoscopic approach of epithelial ovarian tumors of low malignant potential (or
      borderline tumors). STUDY DESIGN: Thirty-four patients with 40 epithelial ovarian
      tumors of low malignant potential treated at Bichat Claude Bernard hospital were
      reviewed. Of these patients, 29 had preoperative sonographic control (85.2%), 19
      (55.8%) had pretreatment serum CA 125 determination, 17 (50%) serum CA 199
      determination and 19 CEA serum levels. Twenty patients (58.8%) had serous tumor
      and 14 (41.2%) had mucinous tumor. Six out of the 20 serous lesions were
      bilateral. Of the patients 31 (91%) had a stage I disease, one had stage II (3%)
      disease and two had stage III (6%) disease. Nine patients (26.5%) had laparotomic
      management, 25 (73.5%) had first laparoscopic management with seven
      laparoconversions (28%). RESULTS: The majority of borderline tumors (67.7%)
      exhibited multilocular aspects and seven patients had benign features (unilocular
      smooth sonolucent). Seven out of the 19 CA 125 serum levels were up to 35 U/ml;
      4/17 CA 199 serum levels were above 40 U/ml but the CEA serum levels were always
      normal. Eighteen patients (52.9%) had radical surgery and 16 patients (47.1%) had
      conservative surgery including 7 cystectomies. Seven patients (20.6%) had
      subsequent laparotomic treatment, (five after laparoscopic management, one after
      laparoconversion management and another one after laparotomic surgery) and no
      residual disease was found. Fourteen patients (41.1%) had preoperative cyst
      rupture (13 during laparoscopic management). Four recurrences in stage I disease
      occurred; one after unilateral salpingo-oophorectomy, three after cystectomy but
      only one recurrence was in ipsilateral ovary. All four recurrences were diagnosed
      by sonographic control and one was associated with CA 125 serum level elevation.
      Ten laparoscopic second look were negative. CONCLUSION: No specific sonographic
      aspect exists for borderline tumors but it is the best way to detect recurrence.
      The preoperative CA 125 serum levels was elevated in 36.8% of patients. The
      conservative treatment including laparoscopic procedure in borderline ovarian
      tumors appears to have a high risk of peroperative rupture but the rate of
      recurrence is similar to laparotomic treatment.

PMID- 8735735
TI  - Gasless laparoscopic gynecologic surgery.
AB  - OBJECTIVE: Evaluate gasless laparoscopic gynecologic surgery as an alternative to
      conventional technique with carbon dioxide insufflation. STUDY DESIGN:
      Retrospective study of 49 cases. RESULTS: Gasless laparoscopic gynecologic
      surgery was successful in 90% of cases. The gasless technique permits the
      surgical team to use the laparoscopic and vaginal approach simultaneously.
      CONCLUSIONS: Gasless laparoscopic gynecologic surgery seems to be a reliable
      alternative to conventional laparoscopy for selected indications.

PMID- 8735737
TI  - Reproductive outcome after hysteroscopic metroplasty.
AB  - OBJECTIVE: To evaluate the reproductive outcome after hysteroscopic metroplasty.
      STUDY DESIGN: We analysed the reproductive outcome of 69 patients, with different
      degrees of septate uterus, undergoing hysteroscopic metroplasty in the outpatient
      infertility clinic of Naples 'Federico II' University. Of the 69 patients, 48 had
      a history of recurrent abortion while 21 had a primary infertility. In all cases
      the procedure was performed by means of the resectoscope. RESULTS: In 97.1% of
      the cases post-operative hysterosalpingogram or hysteroscopic examination showed
      a normal cavity with a little fundal notch. In two cases, second surgery was
      needed. Of the 48 patients affected by repeated abortion, 40 became pregnant
      after the metroplasty whereas, to date, in the infertile group only six out 21
      (29.0%) conceived. We observed a total of 46 pregnancies with two sets of twins.
      Of these, 31 pregnancies (67.4%) were carried to term, five (10.8%) ended in
      preterm delivery, six (13%) ended in spontaneous abortion and four (8.6%) are in
      progress. Cervical cerclage was performed on 13 women. Only one (7.6%) woman with
      cervical cerclage had a preterm delivery, while the preterm delivery rate in
      women without cerclage was 12.1%. The modality of term pregnancy deliveries was
      cesarean section in 48% of the cases and vaginal delivery in the 52%.
      CONCLUSIONS: Our data analysis suggest that the correction of mullerian anomalies
      does not improve the pregnancy rate, but only the pregnancy outcome of the
      patients.

PMID- 8735738
TI  - The effects of hormone replacement therapy on plasma vitamin E levels in post
      menopausal women.
AB  - OBJECTIVE: To measure vitamin E levels in post-menopausal women before and after
      HRT, compared with levels in premenopausal women. DESIGN: Post-menopausal women
      (n = 21) had plasma vitamin E levels measured before treatment and after 6 and 12
      months treatment with HRT (2 mg 17-beta-oestradiol and 1 mg norethisterone
      acetate). The pre-menopausal group (n = 20) had plasma vitamin E levels measured
      at day 15-18 of the menstrual cycle. RESULTS: There was no significant difference
      in vitamin E levels between the pre-menopausal group and the post-menopausal
      group. Plasma vitamin E levels were not significantly altered by 12 months HRT.
      CONCLUSION: Post-menopausal women did not have altered levels of vitamin E
      compared with pre-menopausal women. Similarly HRT has no effect on plasma vitamin
      E levels. We conclude therefore that HRT does not reduce vitamin E levels in a
      similar manner to oral contraceptives and consequently post-menopausal women are
      unlikely to need a vitamin E supplement.

PMID- 8735739
TI  - The impact of woman's age and sperm parameters on fertilization rates in IVF
      cycles.
AB  - OBJECTIVE: To examine the predictive value of different sperm parameters and the
      age of a couple on fertilization rate. MATERIAL AND METHODS: One-hundred six
      consecutive sperm samples were analysed before insemination of oocytes in IVF
      cycles. Sperm count and motility were examined with the Makler Counter Chamber.
      Morphology was evaluated by the eosin nigrosin and giemsa stains. Membrane
      integrity was evaluated by the hypoosmotic swelling test (HOST). RESULTS: Using a
      step-wise logistic regression test the following parameters were all
      significantly correlated with the fertilization rates: sperm concentration after
      a 3-h layering (chi 2 = 15.85, P < 0.001), sperm motility index (chi 2 = 6.12, P
      < 0.0134), woman's age (chi 2 = 6.25, P < 0.012), and the hypoosmotic test (chi 2
      = 6.63, P < 0.01). A fertilization capacity formula was established by using
      these four parameters to predict the fertilization capacity of a couple.
      Significantly lower fertilization rates were detected in elderly women with the
      partner sperm concentration of 7 x 10(6)/ml after 3-h layering, < 30% swollen
      spermatozoa in the HOST and motility index score of < 50. CONCLUSIONS: By the
      aforementioned formula, sperm fertilization capacity can be predicted by using
      simple sperm parameters and women's age. Elderly women with partners who have
      suboptimal sperm parameters reflected by low fertilization capacity scores may
      benefit from micro-manipulation procedures.

PMID- 8735740
TI  - The relation of the gonadotrophin response to chlormadinone according to body
      weight in patients with amenorrhea due to polycystic ovarian syndrome.
AB  - OBJECTIVE: To analyze the influence of weight on gonadotrophin response after
      chlormadinone (hydroxyprogesterone derivative) induced uterine bleeding in women
      with amenorrhea due to polycystic ovarian syndrome (PCOS). DESIGN: A comparative
      study. METHODS: Thirty-six patients with PCOS were classified according to body
      mass index into three weight groups, normal, overweight and obese. Luteinizing
      hormone (LH) and follicle stimulating hormone (FSH) levels were measured during
      amenorrhea and between days 3-5 after a chlormadinone (2 mg/day for 5 days)
      induced uterine bleed. Statistical analysis was performed with Wilcox-on test for
      paired groups and Mann-Whitney U-test for independent groups. RESULTS: Overall
      LH, FSH levels and the LH/FSH ratio fell significantly (P < 0.001, P < 0.01 and P
      < 0.001, respectively) after chlormadinone administration. The LH levels
      decreased in all three weight groups, the LH/FSH ratio only fell in those normal
      and overweight subjects, and FSH did not change in any group. When comparing the
      group with normal weight and those with overweight and obesity no hormonal
      differences were found. CONCLUSION: These results show that chlormadinone has an
      inhibitory effect predominantly over LH secretion which reduces the LH/FSH ratio,
      but this is independent of body weight.

PMID- 8735742
TI  - Effect of chronic stress on estradiol action in the uterus of ovariectomized
      rats.
AB  - The aim of this study was to investigate the development of estradiol (E2)
      effects in ovariectomized rat uterus under chronic stress. The chronically
      stressed rats (swimming and overcrowded cages) were treated with a single
      injection of E2 dipropionate (10 micrograms/ rat, i.m.) in olive oil (0.1
      ml/rat). Control groups of ovariectomized rats included one group treated with
      the same dose of E2 but maintained in stress-free conditions, a second group
      subjected to the same procedure of chronic stress but injected with olive oil
      only, a third group treated with olive oil and maintained in stress-free
      conditions, and a final group which consisted of uninfluenced ovariectomized
      rats. E2 effects were determined by measuring activity of proliferation (mitotic
      index), cellular, nuclear, and nucleolar volumes (morphometry), DNA content
      (Feulgen's method) in luminal and glandular epithelia, stromal cells of
      endometrium at 24, 36 and 48 h after injection of E2 or olive oil. In chronically
      stressed rats treated with E2, at each time point almost all the parameters in
      all the structures were significantly (P < 0.05-0.001) higher, than in unstressed
      E2-treated rats. In E2-untreated rats, the stress did not influence uterine
      tissues. Thus, the chronic stress enhances strongly the E2-induced effects in the
      uterus of ovariectomized rats. It is likely mediated by the changes of some steps
      in the mechanism of estrogen action that leads to the increase in the sensitivity
      of uterine structures to estrogens.

PMID- 8735741
TI  - Thrombophilia and lipid profile in post-menopausal women using a new transdermal
      oestradiol patch.
AB  - OBJECTIVE: To assess the changes, over a 6-month period, in serum lipoproteins,
      apoproteins and coagulation factors, induced in post-menopausal women treated by
      a new transdermal oestradiol patch. METHODS: Fifty-three hysterectomised,
      healthy, post-menopausal women were treated by a new transdermal patch designed
      to deliver 50 micrograms of 17 beta oestradiol per day (Gynaderm, Shire
      Developments). One patch was applied twice weekly. RESULTS: Forty-two patients
      completed the study. There was no significant change in the level of total
      cholesterol, triglycerides, HDL or LDL. There was a significant rise in the level
      of ApoAI after 3 months on therapy but this was not sustained after 6 months;
      there was also a significant drop in the level of ApoAII after 6 months on
      treatment. The changes in ApoB and Lp(a) were not statistically significant.
      There was a significant drop in the level of antithrombin III and of protein S,
      and a significant rise in factor VII. The drop in the level of fibrinogen and of
      protein C were not statistically significant. CONCLUSION: The transdermal route
      of oestradiol administration causes minimal changes in lipoprotein metabolism.
      The statistically significant changes in the thrombophilia profile parallel those
      observed with oral HRT, but, similarly, may not reflect clinical significance.
      The potential of transdermal oestrogens as cardioprotective agents is yet to be
      determined.

PMID- 8735743
TI  - Local cerebral glucose utilization in fetal guinea pigs at 0.75 gestation.
AB  - OBJECTIVE: Using the 2-deoxyglucose method, measurements of local cerebral
      glucose utilization in large fetal animals are very difficult and expensive. To
      circumvent these problems we recently modified the 2-deoxyglucose method for use
      in the fetal guinea pig in utero (Berger et al., J Neurochem 1994; 63: 271-279).
      The present study was designed to measure the rates of local cerebral glucose
      utilization in fetal guinea pigs at 0.75 of gestation. STUDY DESIGN: After
      intravenous injection of 14C 2-deoxyglucose into the dams, local cerebral glucose
      utilization of the fetuses was measured from the time integral of the tracer in
      the maternal plasma and the autoradiographically determined concentration of the
      tracer in various parts of the fetal brain. RESULTS: Fetal cerebral glucose
      utilization was low as compared to adult animals and varied in different brain
      structures from 19 +/- 4 to 29 +/- 7 mumol/100 g/min. CONCLUSION: This study
      demonstrates the feasibility to measure local cerebral glucose utilization in
      undisturbed fetal guinea pigs in utero. We conclude that the low rate of cerebral
      glucose utilization and its small overall variability may reflect the
      neurological immaturity of the fetal brain.

PMID- 8735744
TI  - Mifepristone (RU 486) and its incidence on amniotic fluid volume in near term
      fetal macaque monkeys.
AB  - OBJECTIVE: To evaluate a possible effect of Mifepristone on amniotic fluid volume
      in near term pregnant macaque monkeys. STUDY DESIGN: Six pregnant near term
      monkeys (144 +/- 11 days of gestation) were either treated intramuscularly by
      Mifepristone (10 mg/kg, n = 3) or a placebo (n = 3). Amniotic fluid volumes were
      measured by a dilution technique using blue Evans, just prior to the injection of
      Mifepristone or placebo (t0h) and 24 h later (t24h). RESULTS: Amniotic fluid
      volume (AFV) measured at t0h was found to be statistically the same in placebo
      and Mifepristone-treated macaque monkeys (95 +/- 31 vs. 126 +/- 25 ml,
      respectively, P > 0.05). AFV was found to be lower at t24h when compared to AFV
      at t0h in placebo-treated (88 +/- 31 vs. 95 +/- 31 ml, respectively, P < 0.05)
      and in Mifepristone-treated macaque monkeys (72 +/- 7 vs. 126 +/- 25 ml,
      respectively, P < 0.05). Moreover, the ratio of AFV (t24h/t0h) was found to be
      significantly lower in Mifepristone-treated monkeys when compared to the placebo
      group (57.9 +/- 5.7% vs. 92.2 +/- 2.1%, P < 0.05) indicating a specific effect of
      the antiprogestin on AFV. CONCLUSION: In near term macaque monkeys, Mifepristone
      at 10 mg/kg induces a significant decrease of amniotic fluid volume within 24 h.

PMID- 8735745
TI  - Monoamniotic twin pregnancies. Review of the literature, and a case report with
      vaginal delivery.
AB  - OBJECTIVE: To specify the process of the sometimes difficult diagnosis of
      monoamniotic twin pregnancies, as well as the best practise for delivery of this
      type of pregnancy. METHOD: Using their personal observation (a patient with a
      monoamniotic twin pregnancy, which presented a vaginal delivery at 35 weeks of
      gestation, two girls, in cephalic presentation, without particular problem,
      despite an entanglement of the cord and the existence of a knot), the authors
      established a review of the literature on this subject. RESULTS: Monoamniotic
      twin pregnancies represent a rare possibility. The prognosis is traditionally
      somber: 40-60% mortality, mainly due to pathologies of the cord. The review of
      the recent literature shows that most authors remain in favour of weekly
      ultrasound supervision from the 23rd week and of caesarean section in principle
      at 34 weeks (or from fetal pulmonary maturation). CONCLUSION: In the absence of
      funicular compression signs by colour-doppler, and under the cover of flawless
      obstetrical conditions, vaginal delivery can only be authorized for cases when
      both presentations are cephalic.

PMID- 8735746
TI  - Leiomyosarcoma of the small intestine presenting as a pelvic mass.
AB  - We present a challenging case of differential diagnosis of leiomyosarcoma of the
      small intestine in a patient presented with a pelvic mass. This 43-year-old
      Japanese woman complained of hypermenorrhea and was diagnosed as myoma uteri. She
      underwent partial resection of the ileum with a primary end-to-end anastomosis,
      omentectomy, and appendectomy, as well as a simple hysterectomy and bilateral
      salpingo-oophorectomy. CT and MRI indicated an intestinal tumor at the gaseous
      site. The histological diagnosis was leiomyosarcoma of the small intestine and
      leiomyoma of the uterus. Although such leiomyosarcomas are rare, they can appear
      as pelvic masses and must be differentiated from gynecologic disease.
      Preoperative CT and MRI of the abdomen were useful in obtaining the diagnosis.

PMID- 8735747
TI  - Heterotopic pregnancy in a woman without previous ovarian hyperstimulation:
      ultrasound diagnosis and management.
AB  - Heterotopic pregnancy (HT) in the absence of a previous ovarian hyperstimulation
      is a very rare condition. Transvaginal ultrasonography (TV) in the case of first
      trimester pelvic pain allows a high diagnostic reliability in the identification
      of HT and a successful conservative treatment by means of TV potassium chloride
      injection.

PMID- 8735748
TI  - Trophoblast antigen levels in the first trimester of a trisomy 22 pregnancy.
AB  - We report trophoblast antigen (pregnancy-associated plasma protein-A, PAPP-A;
      free beta-human chorionic gonadotrophin, F beta hCG) expression in a trimosy 22
      pregnancy. Maternal concentrations of these antigens were depressed prior to
      detection of abnormalities by ultrasonography. Immunohistochemical findings were
      consistent with depressed marker expression.

PMID- 8735749
TI  - Potential involvement of yolk sac in teratogenesis.

PMID- 8735750
TI  - Reproductive outcome after expectant management of ectopic pregnancy.
AB  - OBJECTIVE: To study fertility rates following expectant management of clinically
      stable ectopic pregnancies. STUDY DESIGN: Twenty of 33 patients with
      laparoscopically confirmed aborting tubal pregnancies managed expectantly were
      followed for a period of 1-5 years (mean 2.7 years). Excluded were the patients
      not desiring pregnancy, and patients with known impediments to fertility, such as
      age > 40 years and previous infertility, as well as patients lost to follow-up.
      RESULTS: Successful pregnancies occurred in 16 patients (80%); one patient (5%)
      had a repeat ectopic pregnancy. CONCLUSIONS: Expectant management is associated
      with a favorable reproduction outcome.

PMID- 8735751
TI  - Blood pH in the umbilical artery at birth: an analysis of data from patients
      delivered in Hesse between 1986 and 1989.
AB  - OBJECTIVE: Measuring blood pH in the umbilical artery at birth is an important
      means of maintaining obstetrical quality. Consideration of the interrelations
      between low umbilical blood pH and perinatal risk factors may enable
      obstetricians to provide better care of the mother and child during pregnancy and
      delivery. We therefore studied the incidence of measuring blood pH at birth, the
      distribution and normal range of umbilical blood pH at birth, and the correlation
      between umbilical blood pH and pre-, sub-, and postnatal risk factors in patients
      delivered in Hesse between 1986 and 1989. SUBJECTS: Over this period 2053 women
      were delivered between 30 and 32 weeks and 128,654 between 39 and 41 weeks of
      gestation. Each of these two groups was further subdivided according to the mode
      of delivery (spontaneous vaginal delivery; operative vaginal delivery; Cesarean
      section). Of the patients delivered between 39 and 41 weeks of gestation, 24,315
      had exhibited no risk factors during pregnancy or delivery. RESULTS: The overall
      incidence of measuring umbilical blood pH at birth was about 70%, whereas pH
      measurements were taken in only 60% of preterm babies delivered vaginally. The
      percentage of preterm neonates with an umbilical blood pH < 7.10 was considerably
      higher than that of term fetuses (5.0% vs. 1.3%). Of the neonates born of women
      displaying no risk factors during pregnancy and delivery, 22.4% had an umbilical
      blood pH < or = 7.25. In patients delivered at term hardly any correlation was
      found between prenatal risk factors and umbilical blood pH. This contrasted to
      the situation in patients delivered between 30 and 32 weeks of gestation. In most
      subgroups a close correlation could be demonstrated between umbilical blood pH
      and both sub- and postnatal risk factors. No correlation was detected between
      umbilical blood pH and perinatal mortality. CONCLUSION: In view of the aim of
      maintaining and improving obstetrical quality in Hesse, the incidence of
      measuring umbilical blood pH at birth should be increased, especially in preterm
      fetuses. Since 22.4% of all babies from patients exhibiting no risk factors
      during pregnancy and delivery had an umbilical blood pH < or = 7.25, we have to
      reflect once again on the range of 'normal' umbilical blood pH at birth.
      Consideration of the various interrelations between umbilical blood pH and pre-,
      sub-, and postnatal risk factors demonstrated in this study may enable
      obstetricians to reduce the incidence of severely compromised fetuses at birth.

PMID- 8735752
TI  - Treatment of symptomatic polyhydramnios with indomethacin.
AB  - Polyhydramnios carries a poor fetal prognosis with an expected neonatal death
      rate of nearly 30%. Approximately one-fourth of this perinatal mortality is a
      result of the effects of prematurity. The poor outcome with usual management of
      polyhydramnios led us to introduce the therapeutic use of prostaglandin
      synthetase inhibitors so as to decrease amniotic fluid volume and to prevent
      premature labor. Twenty-two women (20 singleton and two twin pregnancies) were
      included in a retrospective study from 1983 to 1992. Indomethacin was given at a
      dose of 3 mg/kg/day. Treatment was started at 28.2 +/- 3.8 weeks of amenorrhea
      and discontinued after 35 weeks. We observed a significant effect of indomethacin
      on amniotic fluid volume and avoided severe preterm delivery in all patients.
      Mean gestational age at birth was 37.5 +/- 1.6 weeks of amenorrhea (range 35.5-39
      weeks). We did not observe any maternal or neonatal side effects of indomethacin
      therapy. However, we reported three neonatal deaths out of 24 infants: two
      related to undiagnosed fetal anomalies (one Nager syndrome and one cerebral
      malformation) and one related to umbilical cord entanglement in a monoamniotic
      twin pregnancy. Since our first report, several open studies supporting our data
      have been published. However, although indomethacin appears to be effective in
      the treatment of polyhydramnios, our goal is to analyze efficacy and side
      effects, so as to define conditions of clinical use.

PMID- 8735753
TI  - Evaluation of the effect of the use of vitamin supplements on vitamin A intake
      among (potentially) pregnant women in relation to the consumption of liver and
      liver products.
AB  - OBJECTIVE: To assess the distribution of dietary vitamin A intake among Dutch
      women aged 16-50 and among pregnant women, and to evaluate the effect of the use
      of a vitamin A (1200 RE) containing multivitamin supplement in terms of
      nutritional and teratogenic risk. STUDY DESIGN: Data from the 2nd Dutch national
      food consumption survey (1992) were used for calculation of the vitamin A intake
      among 1725 16-50 year old women and 58 pregnant women. Calculations were
      performed with and without simulation of the use of a supplement containing 1200
      RE vitamin A. RESULTS: Average vitamin A intake, based on a two-day dietary
      record method, compared quite well with recommended intake levels: 850 RE for the
      16-50 year old non-pregnant (NP) women (RDA: 800 RE), and 990 RE for the pregnant
      (P) women (RDA: 1000 RE), respectively. The use of liver on one of the days under
      survey resulted in high intakes: 60% of the women in this subgroup exceeded the
      'safe upper intake limit' of 3000 RE, while in 23% of the cases intakes were >
      7500 RE. Those not consuming liver or liver products on the days under survey had
      relatively low average intakes [NP (n = 1472): 540 RE; P (n = 46): 720 RE]; about
      70% of the non-liver users had intakes below the RDA. Including the daily use of
      a vitamin A containing multivitamin supplement with 1200 RE resulted in intakes >
      RDA, while only in 2% (NP), respectively 3% (P) of the cases the 'total' intake
      exceeded the 3000 RE level, but remained in all cases below 7500 RE/day. serving
      per day. CONCLUSION: The use of a vitamin A containing (maximum 1200 RE)
      multivitamin supplement can contribute to a controlled and adequate vitamin A
      intake and be considered as safe for pregnant women or women who wish to become
      pregnant, if the consumption of liver is completely avoided and the consumption
      of liver products is limited to maximum one.

PMID- 8735754
TI  - Hyperhomocysteinemia: a risk factor for placental abruption or infarction.
AB  - OBJECTIVE: To establish the prevalence of hyperhomocysteinemia in women with
      placental abruption or infarction. DESIGN: Forty-six women with normal pregnancy
      outcome (controls) and 84 women with placental abruption or infarction (study
      group) were selected, and studied in the non-pregnant state. Homocysteine
      metabolism was investigated by a standardized oral methionine loading test.
      Hyperhomocysteinemia was defined as a concentration of fasting and/or
      postmethionine plasma homocysteine exceeding the estimated 97.5 percentile level
      of the controls. In the fasting state, the vitamin status was investigated by the
      measurement of serum and red cell folate, serum vitamin B12, and whole blood
      pyridoxal-5'-phosphate (PLP, an active form of vitamin B6). RESULTS:
      Hyperhomocysteinemia was diagnosed in four controls (9%) and 26 women of the
      study group (31%, P < 0.05). The median concentrations of the vitamins studied
      were significantly lower in women of the study group as compared to the controls,
      except for red cell folate, where the median concentration was comparable in both
      groups. The median concentration of fasting plasma homocysteine, unlike post
      methionine plasma homocysteine, was significantly higher in women who experienced
      placental abruption or infarction in their first pregnancy than in women who had
      the same event after one or more uncomplicated pregnancies. CONCLUSION:
      Hyperhomocysteinemia is associated with placental abruption or infarction.

PMID- 8735755
TI  - Dynamic and steady state response of heart rate to orthostatic stress in
      normotensive and hypertensive pregnant women.
AB  - We determined the dynamic and steady state responses of heart rate (HR) to
      orthostatic stress (standing up) in normotensive and hypertensive pregnant women.
      Using a continuous recording with servo-photosphygmography, HR response to change
      in posture from left lateral recumbent position to standing was analysed. The
      subjects were divided into five groups comprising: Groups I, II and III:
      normotensive pregnant women in each of the three trimesters of pregnancy (total n
      = 77); Group IV: women with gestational proteinuric hypertension (GPH) in the
      third trimester (n = 16); Group V: age-matched non-pregnant normotensive controls
      (n = 15). The HR reacted with a typical overshoot response to this orthostatic
      change with HR rising to a peak and then settling to a new but higher steady
      state. Change in steady state HR from lying to standing (delta HR), rate of rise
      of HR in response to standing (i.e. the acceleration slope (HRon)), and rate of
      fall of HR after reaching the peak (i.e. deceleration slope (HRoff)) were
      evaluated from standing heart rate time curves. HRon in response to standing
      showed a downward trend with gestation (ANOVA, P < 0.05) in normotensive gravida.
      The deceleration slope (HRoff) showed a distinct gestational age-related decrease
      from first to third trimester in normotensive women (ANOVA, P < 0.01). The most
      striking observation was that the slope of HRoff for the GPH group was
      significantly steeper than that of normotensive women of comparable gestational
      age (unpaired t-test P < 0.01) and approximated to that of the non-pregnant
      group. The difference in HR response between normotensive women and those with
      GPH in the third trimester suggests it may have potential as a new marker for pre
      eclampsia.

PMID- 8735756
TI  - Survey of the management of third stage of labour in The Netherlands.
AB  - The standard practice during the third stage of labour of Dutch midwives and
      obstetricians was elucidated by a questionnaire mailed to all Dutch midwives and
      obstetricians. Prophylactic oxytocics in the third stage are used as a routine by
      55% of the obstetricians and only 10% of the midwives. Oxytocin is the drug of
      first choice. CONCLUSION: Routine use of prophylactic oxytocics in the third
      stage is not the standard practice in the Netherlands. Obstetricians are much
      more likely to use prophylaxis than midwives.

PMID- 8735757
TI  - Serum and peritoneal CA-125 levels as diagnostic test for endometriosis.
AB  - OBJECTIVE: To evaluate the clinical utility of CA-125 in the diagnosis of
      endometriosis and to compare the sensitivity of the serum and the peritoneal test
      as indicator of disease. STUDY DESIGN: Peritoneal fluid was obtained at
      laparoscopy. The quantitative determination of CA-125 in serum and in peritoneal
      fluid was performed by IRMA-mat CA-125 'two-step method', a two-site
      immunoradiometric assay, using 35 and 60 U/ml as cutoff. SETTING: Second
      Department of Gynecology and Obstetrics, Second University of Naples, Italy.
      PARTICIPANTS: A total of 26 women infertile undergoing diagnostic laparoscopy
      that exhibited endometriosis in 14 patients, normal pelvis in 12 patients
      (control group). INTERVENTIONS: None. RESULTS: CA-125 levels in peritoneal fluid
      were higher than those found in serum and were significantly elevated (P < 0.05),
      when compared with the control group, both in women with endometriosis stage I-II
      and stage III-IV. In serum, CA-125 levels increased only in advanced stage of
      endometriosis. CONCLUSIONS: Levels of CA-125 in peritoneal fluid seem to be a
      more sensitive indicator of disease than serum levels (0.86 vs. 0.36), especially
      in early stage endometriosis (0.80 vs. 0.20) which tends to be overlooked by the
      CA-125 serum test.

PMID- 8735758
TI  - Immunohistochemical and hysteroscopic assessment of postmenopausal women with
      uterine bleeding whilst taking Tibolone.
AB  - The gonadomimetic steroid Tibolone, is currently widely used for the treatment of
      menopausal symptoms. Up to 20% of women have been reported to have episodes of
      bleeding whilst on therapy. We investigated 37 cases who experienced bleeding
      episodes whilst on Tibolone and compared these to six cases who experienced no
      bleeding whilst on therapy and who underwent similar investigations in the course
      of a clinical study. All women underwent a diagnostic hysteroscopy and an
      endometrial biopsy, under a local anaesthetic. The endometrium was assessed by
      histology and with immunohistochemical markers for cellular proliferation (Ki67,
      PCNA), Heat Shock Protein 27 (HSP27) and bcl-2. There were 17 women with
      intracavitary lesions on hysteroscopy (including one in the control group), 10
      with polyps, five with fibroids, two with congenital uterine anomalies.
      Histological diagnosis was not obtained in 16 cases. The high incidence of
      uterine polyps in the group who bled on Tibolone suggests an etiologic relation.
      The staining pattern with HSP27 demonstrated an oestrogenic effect. There were no
      differences in the bcl-2 immunoreactivity between those who bled and those who
      did not bleed on treatment which suggests absence of a link. Similarly, there
      were no differences in the expression of the proliferation markers. We conclude
      that episodes of bleeding in patients receiving Tibolone for hormone replacement
      therapy, whilst warranting investigation, should not cause undue concern.

PMID- 8735759
TI  - Pain relief during and following outpatient curettage and hysterosalpingography:
      a double blind study to compare the efficacy and safety of tramadol versus
      naproxen. Cobra Research Group.
AB  - OBJECTIVE: To compare the analgetic efficacy and side-effects of Naproxen and
      Tramadol following the outpatient VABRA aspiration or hysterosalpingography.
      SETTING: Ninety-one patients from the gynaecology clinics of two university
      hospitals and one municipal-teaching hospital. DESIGN: Multicentre double blind
      randomized clinical trial. Computerised randomisation, stratification per-centre.
      METHODS: Semiquantitative assessment of the two drugs was performed by the
      patient and the gynaecologist using a 1- to 6-point scale. Pain, stress and well
      being was scored by the patient using the visual analog scale (VAS) and the
      verbal description scale (VDS), ranging from 0 (good) to 100 (bad). Side-effects
      during the first 24 h postoperatively were recorded by the patient in a diary.
      RESULTS: The analgetic efficacy (pain, stress and well-being) of Naproxen and
      Tramadol was identical. Subjective assessment by the patient and the doctor also
      revealed no differences between Naproxen and Tramadol. Side-effects of Tramadol,
      however, were significantly more severe than those of Naproxen and this
      phenomenon was responsible for a lower ability to proceed with normal activities
      in the Tramadol group. CONCLUSION: Tramadol is a good alternative for Naproxen at
      outpatient VABRA or HSG procedures when Naproxen is contra-indicated.

PMID- 8735761
TI  - The evaluation of morphological abnormalities of human spermatozoa in fertile and
      infertile men.
AB  - Spermatozoal morphology in semen from 114 fertile men, 107 infertile men with
      varicocele and 35 infertile men with infection of the accessory genital organs,
      aged from 18 to 53 years were evaluated by Papanicolaou-stained smears in order
      to investigate: (a) the frequency of abnormalities in the neck and tail of
      spermatozoa with an abnormal head and (b) the ability of prediction of the
      morphology of one sperm part when the morphology of another part is known. The
      investigation showed that: (1) morphological abnormalities in the neck are
      significantly higher (P < 0.001, P < 0.01), when the head was abnormal, compared
      to spermatozoa with a normal head in fertile men and in men with varicocele,
      respectively; (2) morphological abnormalities in the tail are also higher (0.05 <
      P < 0.1) in spermatozoa with an abnormal head in men with infection; (3) the
      proportional reduction of error (PRE) was low in all cases. Our results show that
      spermatozoa with abnormal heads more often present morphological abnormalities of
      their counterparts compared to spermatozoa with normal heads. Nevertheless, no
      prediction can be made on the nature of the morphology of a part of a
      spermatozoon on the basis of knowledge of its morphology of another part.

PMID- 8735760
TI  - First line immunochemotherapy with cisplatin-based protocol by intraperitoneal
      and intravenous routes in ovarian cancer: technique and results of 82 cases.
AB  - OBJECTIVES: The aim of this study, initiated in 1982, was to determine the
      feasibility and the interest of a first-line immunochemotherapy delivered by
      intraperitoneal (i.p.) and intravenous (i.v.) routes combined in ovarian cancer.
      STUDY DESIGN: Eighty-two naive patients with a common epithelial cancer entered
      the study from January 1982 to December 1990 (median follow up > 70 months). For
      i.p. infusion, we used a simple lumbar puncture needle left in situ for < 2 h.
      The first 18 patients received monthly by i.p. route: Adriamycin (DXR) 40 mg/m2,
      Fluorouracil 1000 mg/m2, Cisplatin (CDDP) 90 mg/m2, Bleomycin 30 mg -DGZ (extract
      of vibrio cholerae) 60 mg/m2. For the remaining 64 patients Aracytin 500 mg/m2
      replaced DXR and the dose of CDDP was more than doubled (200 mg/m2) thanks to the
      use of sodium thiosulfate. All 82 patients received Ifosfamid 1300 mg/m2
      intravenously. RESULTS: Local toxicity consisted in one subcutaneous abscess and
      one bacterial peritonitis out of 1508 abdominal punctures. Stage III turned out
      to be the most interesting group to evaluate the efficacy of a first-line
      protocol. In this group 34 out of 47 patients (72.3%) who underwent an initial
      incomplete surgery were in complete remission (CR) at second-look. Nevertheless,
      21 out of the 34 patients in CR relapsed (61.7%) and 14 died (43.2%). CONCLUSION:
      These results show the efficacy of our regimen administered i.p., and the safety
      of the delivery by a simple needle which avoids the complications of the
      implantable systems. Nevertheless, the usefulness of a systematic second-line
      chemotherapy (Paclitaxel?), despite a prognosis situation as favourable as a CR
      at second-look, must be taken into consideration.

PMID- 8735762
TI  - Gaucher's disease and pregnancy.
AB  - A 24-year-old primigravid woman with adult type Gaucher's disease was admitted at
      28 weeks of pregnancy. She was asthenic and the abdomen was markedly protuberant
      due to hepatosplenomegaly. A conservative approach with close monitorization of
      both mother and baby was planned. On the 39th week of pregnancy a healthy female
      baby of 3000 g was delivered via cesarean section. Apart from mild hematological
      complications, the pregnancy, the delivery and the puerperium were uneventful.

PMID- 8735763
TI  - Hyperreactio luteinalis: intraoperative finding during a cesarean section in a
      twin pregnancy.
AB  - Bilateral ovarian enlargement can be found in the course of a cesarean section.
      It is necessary to keep in mind that hyperreactio luteinalis is a benign
      condition, because the appropriate management is conservative. We present an
      unexpected, intraoperatively diagnosed case of bilateral ovarian cystic-solid
      tumours (13 cm) in a twin pregnancy.

PMID- 8735764
TI  - Endometrial ossification successfully treated by hysteroscopic resection.
AB  - BACKGROUND: Endometrial ossification is a rare condition. The common feature in
      most reported cases is a previous history of abortion and retention of fetal
      bones. Few cases of endometrial ossification can be explained by osseous
      metaplasia. Clinical presentation may include abnormal vaginal bleeding or
      discharge, dysmenorrhoea, pelvic pain, and secondary infertility. Hysterectomy or
      dilation and curettage have been the usual therapeutic methods used. Recently,
      some cases have been treated by means of hysteroscopic resection. CASE: We report
      a case of endometrial ossification in a woman who presented with dysmenorrhoea,
      dyspareunia and pelvic pain. The patient had a pregnancy voluntarily terminated
      at 16 weeks. Five subsequent routine annual gynaecological exams, including
      ultrasonographies, were normal. A new gestation was also voluntarily terminated
      at 6 weeks. One month later the patient started with clinical manifestations.
      Ultrasonograms performed 4 months after the second abortion revealed a strong
      uterine echogenic band. Bone tissue was successfully removed by hysteroscopic
      resection. CONCLUSION: This case adds further evidence favouring new bone
      formation in the uterus as a pathogenic mechanism for endometrial ossification
      and illustrates the feasibility of hysteroscopic treatment for this condition.

PMID- 8735765
TI  - Reverse end-diastolic uterine artery velocity in a pregnant woman complicated by
      mild preeclampsia and severe growth retardation.
AB  - In a pregnant woman with mild preeclampsia and severe intrauterine growth
      retardation, a reverse end-diastolic flow velocity was detected in both uterine
      arteries by colour Doppler ultrasound at 30 weeks 4 days of pregnancy. During
      follow up, both umbilical and internal iliac arteries also showed reverse end
      diastolic velocity waveforms and the fetus died in utero at 33 weeks gestation.

PMID- 8735766
TI  - Twenty-day cerebral and umbilical Doppler monitoring on a growth retarded and
      hypoxic fetus.
AB  - In one growth retarded and hypoxic fetus, the cerebral and umbilical hemodynamic
      changes were assessed (by Doppler), daily over 20 days. The fetal brain was
      investigated by magnetic resonance imaging (MRI) close to the delivery, and
      because the fetus died at delivery we performed an anatomical study of the fetal
      brain. The evolution of the fetal hemodynamics (day by day) was interpreted
      according to the MRI findings and the clinical findings. During the period of
      observation (under sustained hypoxia) the fetal deterioration was characterized
      by: (a) the progressive development of the oligohydramnios (190d), (b) the
      disappearance of the vascular reactivity (eight successive cerebral resistance
      index (RI) constant at 194d), (c) the occurrence of fetal heart rate
      decelerations (199d), and finally (d) the increase of the cerebral vascular
      resistances with reduction of the brain perfusion (204d). The anatomical study of
      the brain showed a periventricular congestion however the histology revealed
      hypoxic lesions like gliosis and a marked vasodilation of the anterior and middle
      cerebral arteries. Finally in addition to single Doppler measurements performed 1
      week before delivery (for prediction of fetal outcome), one can suggest to use
      the 'loss of fluctuation of the cerebral RI' to identify the beginning of the
      period of very high risk for the fetus. Such hypothesis may have to be confirmed
      on a larger number of pathological pregnancies.

PMID- 8735767
TI  - Ectopic pregnancy three times in line of which two advanced abdominal
      pregnancies.
AB  - Three consecutive ectopic pregnancies were diagnosed in one patient. Two
      pregnancies (one following IVF-ET) proceeded as abdominal pregnancies till the
      third trimester of pregnancy. Neither abdominal pregnancies had been diagnosed
      prior to surgery.

PMID- 8735768
TI  - Joint workshop on perinatal bereavement Luxembourg 23-24 September 1995. European
      Midwives Liaison Committee, European College of Obstetrics and Gynaecology.

PMID- 8735769
TI  - Malthusian parameter on the Finnish population in the 20th century.
AB  - We were interested in studying a demographic indicator, the Malthusian parameter
      which had not been investigated earlier in the case of the Finnish population. We
      computed the Malthusian parameter with a known renewal equation, which is, as
      usual, approximated on discrete data by using normal distribution, on the Finnish
      population in the 20th century. The data was collected from the abundant official
      statistical sources which are known to be accurate and reliable in Finland. In
      addition to this parameter we computed the gross and net reproduction rates, the
      total fertility index, and the mean and variance age of females at child-bearing.
      The Malthusian parameter seems to be a rather good means of characterizing the
      development of the population. If the parameter is positive for long enough, the
      population tends to grow. If it is negative, as has been the case in Finland
      since 1969, the population starts to diminish sooner or later. On the other hand,
      it cannot take all factors into account. For instance, because of still
      increasing lifetime and also because of a relatively large quantity of females at
      the reproductive age the population is not yet decreasing in Finland. In any
      case, the Malthusian parameter forecasts the future trend of the decreasing
      population.

PMID- 8735770
TI  - Calculating confidence intervals for summary measures of individual curves via
      nonlinear regression models.
AB  - In biomedical research data are often collected serially over time. Hence, the
      main outcome is represented by response curves. A suitable approach to analyse
      such data is given by summary measures describing the main features of the
      response curves. An important issue is the precision of the estimated summary
      measures, which can be represented by confidence intervals. However, since
      summary measures frequently cannot be obtained via linear relationships, the
      calculation of confidence intervals involves some special considerations. In this
      paper attention is focused on unimodal response curves. Important summary
      measures for this type of response curves are the curve maximum (Cmax), the time
      to curve maximum (tmax), and the area under the curve (AUC). These summary
      measures can be calculated from the parameters of nonlinear regression models
      fitted to the data. Since the summary measures are nonlinear functions of the
      regression coefficients the multivariate delta method is used to derive formulas
      for the standard errors and confidence intervals of the summary measures. The
      method is illustrated by application to pharmacodynamic data.

PMID- 8735772
TI  - Security considerations for present and future medical databases.
AB  - In this paper we consider the security of medical databases. We give an overview
      of the security problems and the possible available mechanisms for the prevention
      of security compromises. Many of the security problems are common to all
      databases. However, the problem of data inference from statistical queries is
      particularly pertinent to medical databases and consequently we treat this
      problem in more detail. The paper concludes with a proposal for a Security
      Subsystem in a database management system.

PMID- 8735771
TI  - An expert system based on causal knowledge: validation on post-cardiosurgical
      patients.
AB  - A new expert system for the analysis of post-cardiosurgical patients in Intensive
      Care Units is described, and a preliminary validation performed. The inference
      engine employs a hybrid reasoning method which integrates quantitative and
      qualitative simulation techniques in an original manner. The long-term knowledge
      consists of a causal network which reproduces the main relationships between
      physiological quantities involved in the course after cardiac surgery. Emphasis
      has been given to respiratory and metabolic, as well as cardiovascular quantities
      both in the systemic and pulmonary circulations. Preliminary system validation
      has been performed on a set of 40 cardiosurgical patients, previously classified
      either at normal-risk (17 patients) or at high-risk (23 patients) by means of
      statistical classification techniques. In most cases, predictions of the expert
      system substantially agree with those provided by the more traditional
      statistical method. The system, however, is also able to furnish detailed
      explanations on the possible physiological causes responsible for the patient
      status. In particular, simulation results indicate that a reduction in the
      cardiac index (19 cases) and an increase in the oxygen utilization coefficient
      (19 cases) are the most critical alterations in the high-risk patients. The
      system imputes the reduced cardiac index to a rise in total systemic resistance
      (15 high-risk patients), a decrease in cardiac strength (2 high-risk patients) or
      an insufficient filling volume of the systemic circulation (4 high-risk
      patients). Furthermore, in 6 high-risk patients the depressed cardiac outflow
      occurs with a reduction in the arterial oxygen content, mainly imputable to an
      insufficiency of blood hemoglobin content. Finally, two examples of the complete
      expert system explanatory capabilities are shown with reference to a pair of high
      risk patients and discussed.

PMID- 8735773
TI  - Establishing a reliable visual function test and applying it to screening optic
      nerve disease in onchocercal communities.
AB  - The computer Controlled Video Perimetry (CCVP) is a computer screening test for
      detecting visual function loss caused by onchocerciasis, glaucoma, etc. Installed
      on portable computers, the CCVP has been shown to be high acceptability in field
      community investigation. However, it is regarded to be difficult in obtaining
      reliable results from portable computer screening tests because of human
      behavioural variants and the lack of standard testing environment. In this paper,
      we propose an architecture for implementing a more reliable CCVP system. In
      particular, a self-organising neural network is applied to manage measurement
      noise caused by behavioural factors. A control unit is introduced to manage the
      overall behaviour of the system. The integrated test system has been used to
      screen optic nerve disease in onchocercal communities of rural Nigeria and the
      experimental results obtained from a large number of test records are very
      encouraging: reliable results from volatile test environments may be obtained
      using the proposed method.

PMID- 8735774
TI  - Aflatoxin destruction by microwave heating.
AB  - Microwaves were used in the present work in order to destroy pure aflatoxins
      (model system), and yellow corn and peanuts containing aflatoxins (food system).
      Pure aflatoxins (B1, B2, G1 and G2) were individually coated on a silica gel and
      exposed to microwaves at various power settings and periods. The same technique
      was adopted for peanuts and yellow corn deliberately infected by Aspergillus
      flavus. The aflatoxins were extracted, fractionated by thin-layer chromatographic
      technique and quantitatively determined by spectrodensitometry. In all cases, the
      content of different aflatoxins in the deliberately infected yellow corn was in
      the decreasing order B1 = G1 > B2 > G2. Infected peanuts were characterized by
      the highest B1 level, being approximately 3, 2, and 4.4 times as great as that in
      B2, G1 and G2, respectively. The rate of aflatoxin destruction of model and food
      systems increased with the increase of microwave oven power setting (low,
      moderate and high) and exposure time to microwaves.

PMID- 8735775
TI  - Does serum albumin/phospholipid index better reflect overall protein status in
      man?
AB  - Serum albumin concentration is a commonly used, but inadequate index of protein
      status in man. A study of serum lipid changes in malnourished children reported a
      progressive increase in serum phospholipid concentration with deterioration of
      protein status in the children. This led us to assess the usefulness of serum
      albumin/phospholipid index (API) in groups of healthy young adults, malnourished
      children, and their age-and-sex-matched well-nourished controls. We found that
      API discriminated between malnourished and well-nourished children. There was no
      difference between the index for well-nourished children and adults in spite of
      differences in body sizes. However, since serum albumin showed a similar
      discrimination between malnourished and well-nourished children, API may possibly
      not be superior to serum albumin in the assessment of protein status in man.

PMID- 8735776
TI  - Iron fortification of domestic drinking water to prevent anemia among low
      socioeconomic families in Brazil.
AB  - Iron deficiency anaemia is a most common micronutrient deficiency affecting
      mostly the low socioeconomic populations of the developing world. The objective
      of this study was to evaluate the feasibility of iron fortification of household
      drinking water to prevent iron deficiency anaemia among members of the low
      socioeconomic families of Southern Brazil. A total of 21 low socioeconomic
      families representing 88 subjects including 1-6 years old children whose
      haemoglobin level was between 10 and 12 g/dl were selected to participate in this
      study. Nine families in the control group were supplied with placebo solution and
      12 families in the experimental group were supplied iron solution with ascorbic
      acid to be added to their domestic drinking water over a period of 4 months. The
      feasibility and acceptability of iron fortified drinking water was assessed
      through home visits and questionnaires. Blood samples were collected at the
      beginning and after 4 months of the study for the determination of haemoglobin
      and serum ferritin levels. The results of this study indicated that iron
      fortified drinking water was well received by the low socioeconomic families and
      that it was effective in improving the haemoglobin and serum ferritin levels. It
      can be concluded from this study that iron fortification of household drinking
      water is a simple and effective alternative for developing countries along with
      other technological approaches to iron fortification of foods.

PMID- 8735777
TI  - Are dietary recommendations for dietary fat reduction achievable?
AB  - Despite several sets of dietary guidelines aimed at reducing fat intakes in the
      UK populations the actual fat intake in the UK has remained remarkably constant
      over the last decade. It is therefore of utmost importance to understand why the
      advice of the 1980s was not taken on board by the nation, to enable the
      achievement of current nutritional targets for dietary fat set for 2005. The
      nature of the diets of those individuals in the UK who have low fat intakes in
      line with the dietary goals are considered here, with the aim to increase our
      understanding of how the goals can be achieved in the free-living population.
      This paper postulates that a low fat diet will be easier to achieve, more
      palatable and hence more acceptable to the consumer if the dietary fat is
      replaced with a mixture of energy from sugar and starch. Further research is
      required to gain a greater understanding of what type of dietary composition will
      enable the free-living population to achieve a reduction in their dietary fat
      intake. This in turn will allow the dissemination of appropriate nutritional
      advice in the future and inform product development initiatives in the food
      industry.

PMID- 8735778
TI  - Serum antioxidant potential, and lipoprotein oxidation in female smokers
      following vitamin C supplementation.
AB  - A single blind placebo controlled trial was carried out to assess the effect of
      high dose vitamin C supplementation on the antioxidant potential, and extent of
      lipoprotein oxidation of serum in female smokers. Sixteen apparently healthy
      subjects were randomised into two groups of eight. One group received 1 g of
      vitamin C for 14 days the other group received a placebo for 14 days. Serum
      antioxidant potential (TRAP) was measured and lipoprotein oxidation was assessed
      by measuring serum malondialdehyde like material. Despite significant increases
      in serum C concentrations in the supplemented group, serum TRAP values did not
      change significantly over the course of the trial. Serum malondialdehyde like
      material also failed to show any temporal variation.

PMID- 8735779
TI  - Lipid peroxidation: a review of causes, consequences, measurement and dietary
      influences.
AB  - In this review the process of lipid peroxidation and the atherogenicity of
      peroxidied lipids are discussed. Recent findings with regard to the effect of
      selected dietary factors on susceptibility of lipids to oxidative stress and on
      antioxidant defences are analysed with particular reference to their potential
      use in the prevention and treatment of atherogenesis and, by extension, coronary
      heart disease. Laboratory methods of assessing antioxidant defences, lipid
      peroxidation and the effects of lipid peroxidation are also reviewed and
      discussed with particular reference to their ability to assess in vivo oxidative
      stress and lipid peroxidation status. A range of oxidative stress indices are
      presented and their limitations discussed, but the main focus is on the most
      commonly used laboratory test for lipid peroxidation, the thiobarbituric acid
      reacting substances (TBARS) test. Finally, the influence of selected dietary
      factors on measured peroxidation status is discussed, with particular reference
      to the antioxidant vitamins C (ascorbic acid) and E (alpha tocopherol) and the
      type of fatty acids (mono- and poly-unsaturated) in the diet.

PMID- 8735781
TI  - Relationship between birth weight and biochemical measures of maternal
      nutritional status at delivery in Bangladeshi urban poors.
AB  - A cross-sectional study was carried out to investigate relationship of birth
      weight with selected biochemical indices of nutritional status of mothers at
      delivery in poor urban population of Dhaka, Bangladesh. One hundred and fifty one
      pregnant women of known gestational length, aged 20-30 years, who attended a
      local maternity hospital for delivery participated in this study. All of them
      were free from any pregnancy complications or diseases, and delivered a singleton
      fullterm baby. Socio-economic and obstetric history were taken by interview.
      Anthropometric data and blood samples were collected on the same day. Twenty per
      cent of the participants were anaemic (Hb < 11.0 g dl-1), 49% had subnormal (<
      4.0 g dl-1) serum albumin and 32.5% had serum vitamin A lower than adequate level
      (< 30.0 micrograms dl-1). Mothers who gave birth to low birth weight babies had
      lower levels of haemoglobin (P = 0.06), serum albumin (P = 0.02) and serum
      vitamin A (P = 0.05) at delivery compared with the mothers who gave birth to
      normal weight babies. After adjustment for various confounding factors, only
      serum albumin level remained significantly lower in the mothers of low birth
      weight babies. Using multiple regression analysis for birth weight, the overall F
      ratio was calculated to be 12.5 and was highly significant (P = 0.0000). The
      adjusted R2 was 0.32. Gestational age, father's occupation, mother's body weight
      and serum albumin level were found to have significant independent effect on
      birth weight.

PMID- 8735780
TI  - Effect of different post-harvest treatments on antinutritional factors in seeds
      of the tribal pulse, Mucuna pruriens (L.) DC.
AB  - The effect of soaking, cooking and autoclaving on the levels of certain
      antinutritional factors present in the tribal pulse, Mucuna pruriens, were
      studied. The amount of reduction of total free phenolics was found to be greater
      in sodium bicarbonate solution (56%) compared to distilled water (47%); subjected
      to cooking and autoclaving these were further reduced to 49%. Autoclaving (45
      min) significantly reduced the tannin content (71%). Insignificant reduction in
      content of L-DOPA was observed in all the processes. Distilled water soaking was
      found to be ineffective in eliminating lectin activity; whereas very significant
      reduction was noticed against all the human blood groups ABO without any
      specificity in samples subjected to cooking and autoclaving. Soaking in distilled
      water was more effective (27% reduction) than sodium bicarbonate solution (17%
      reduction) in lowering the contents of phytic acid. Cooking for 90 min and
      autoclaving for 45 min resulted in eliminating phytic acid to the extent of 18%
      and 44%, respectively. Loss of HCN was greater under autoclaving (75%) than the
      other processes studied. Of the three oligosaccharides analysed, soaking effected
      maximum reduction in the level of stachyose followed by verbascose and raffinose.
      Autoclaving effected greater reduction (59-81%) compared to ordinary cooking (40
      60% reduction). Of all the different treatments studied, autoclaving seemed to be
      the best method in eliminating the investigated antinutrients more efficiently
      except L-DOPA.

PMID- 8735782
TI  - Melanotrope dopamine D2 receptor isoform expression in the developing rat
      pituitary.
AB  - This study measured melanotrope mRNA and protein expression for the dopamine D2
      receptor, and its long isoform, in relation to the appearance of dopamine in
      axons of the postnatal rat pituitary intermediate lobe. At postnatal day 2, prior
      to the onset of dopaminergic innervation, D2 receptor (D2T) mRNA was expressed
      heterogeneously in a subpopulation of melanotropes which also expressed the long
      isoform (DL). The D2L mRNA appeared to be predominant during early postnatal
      development, since the D2T probe, which did not discriminate between the
      isoforms, and the D2L probe hybridized generally to the same cells, as
      demonstrated in serial sections. Immunohistochemical methods, using two different
      antisera for the D2T receptor, however, indicated a low level of protein in most
      melanotropes. Localization of D2L protein corresponded well to D2T receptor mRNA
      distribution. At day 10, representing a time when dopamine is present in axons
      throughout the lobe, both D2T receptor mRNA and protein were detected in a
      significantly larger population of melanotropes than those expressing D2L mRNA
      and protein. This suggests the appearance of detectable short isoform (D2S) mRNA
      in virtually all melanotropes and implicates dopamine as a possible signal for
      increasing D2S isoform mRNA expression.

PMID- 8735783
TI  - Permeability function related to cerebral microvessel enzymes during ageing in
      rats.
AB  - Cerebral microvessels from rats were prepared and characterized by their
      enrichment of specific markers, namely alkaline phosphatase (AP) and tau-glutamyl
      transpeptidase (tau-GT). Further, it was observed that AP and tau-GT registered
      marked increase in aged rats. On the contrary, lactate dehydrogenase (LDH)
      activity decreased with the increasing age. Monoamine oxidase A activity in the
      microvessels decreased with age whereas MAO-B moved in the reverse direction. No
      noticeable change was seen in acetyl-cholinesterase activity with increasing age
      of rats.

PMID- 8735784
TI  - Ontogenic development of membrane lipids in the chick optic lobe.
AB  - The developmental profiles of the lipid composition and their de novo synthesis
      and remodelling in the optic lobe of the chicken were studied. The 32P
      incorporation to phospholipids showed an active de novo synthesis mainly of
      phosphatidylinositol and of a particular fraction of phosphatidylcholine during
      the early stages of the embryo development, concomitantly with the beginning of
      synaptogenesis. This de novo synthesis of phospholipids strongly increased at
      hatching. On the other hand, phosphatidylinositol presented an active lipid
      exchange (acylation-deacylation) in the early stages of embryogenesis, indicating
      a strong incorporation of 14C-arachidonic acid during this period, followed by a
      fast drop in specific activity. Two different fractions of phosphatidylcholine
      were isolated by high-performance thin-layer chromatography with a different
      profile of fatty acid composition, disclosing their different physicochemical
      behavior, metabolic activities and evolution during embryogenesis. 32P
      incorporation into phosphatidylethanolamine remained very low during the earliest
      stages of embryogenesis, showing an increase when the process of synaptogenesis
      began, until hatching, when radioactivity reached a plateau. 14C-arachidonic acid
      incorporation into phosphatidylethanolamine was minimal. Furthermore, the
      phosphatidylethanolamine pool was progressively enriched in its ethanolamine
      plasmalogen throughout the development. Chromatographic analysis of lipid
      extracts showed the presence of cerebroside traces after 16 days of embryo
      incubation. At hatching, a remarkable increase in non-hydroxylated cerebrosides
      was observed concurrently with the appearance of hydroxylated ones. These
      glycosphingolipids, as well as the sulfatides, were markedly increased in the
      lipid extracts of optic lobes of adult animals, indicating the progressive
      development and maturity of the myelin sheath.

PMID- 8735785
TI  - Dependence of cranial motor neuron formation on ventromedial brain stem.
AB  - The formation of motor neurons in the spinal cord is dependent on inductive
      signals from the floor plate and notochord. Motor neurons in the brain stem, on
      the other hand, develop in the absence of both structures. This suggests that
      either the germinal epithelium is specified intrinsically to form specific
      cranial motor nuclei or that the inductive signals for the formation of cranial
      motor neurons arise from some other structure. These possibilities were
      investigated experimentally by using the formation of trochlear motor neurons in
      the midbrain of duck embryos as a model system. The trochlear motor neurons,
      which form the nucleus of the fourth cranial nerve, developed normally after
      early damage to the prospective germinal epithelium, suggesting that it is
      unlikely to be specified intrinsically to form these cranial motor neurons.
      Instead, their development was found to be dependent on the cells within, or
      associated with, the ventromedial region of the brain stem, as the extirpation of
      this region results in the absence of motor neuron formation. These results show
      that structures other than the floor plate and notochord provide inductive
      signals for the cellular differentiation and patterning of the developing central
      nervous system. The raise the possibility that the inductive signals for motor
      neuron differentiation in the spinal cord and the brain stem may not be
      necessarily identical.

PMID- 8735786
TI  - Increase in nitric oxide synthase and NADPH-diaphorase in the adrenal gland of
      streptozotocin-diabetic Wistar rats and its prevention by ganglioside.
AB  - Levels of nitric oxide synthase (NOS) and NADPH-diaphorase in adrenal glands of
      streptozotocin-diabetic rats of 8 and 12 weeks' duration compared with control
      rats were assessed with histo-chemical and biochemical techniques. Adrenal glands
      from streptozotocin-diabetic rats of 8 weeks' duration treated with ganglioside
      were examined also. In the adrenal medulla of 8-weeks- and 12-weeks-diabetic
      rats, NOS-immunoreactive nerve fibres were increased and decreased, respectively;
      additional NOS-immunoreactive and NADPH-diaphorase stained cells, which appeared
      to be cortical cells, were located in medulla and cortex compared with controls.
      Increased intensity in NADPH-diaphorase staining of the cortical cells of
      diabetic rats was observed also. Ganglioside treatment of the 8-weeks-diabetic
      rats prevented the diabetic-induced increase in NOS-immunoreactive nerve fibres.
      Also, it reduced most of the increase in the NOS-immunoreactive and NADPH
      diaphorase stained cells and the intensity of NADPH-diaphorase staining of
      cortical cells. With biochemical assay, a significant increase in NOS activity
      was found in the adrenal glands from 8-weeks-diabetic rats, and this increase was
      reduced by ganglioside treatment in four out of six diabetic rats. In summary,
      streptozotocin-induced diabetes causes an initial increase in the levels of NOS
      and NADPH-diaphorase in the adrenal gland of rat, which was prevented by
      ganglioside treatment.

PMID- 8735787
TI  - Lead alters structure and function of mouse flexor muscle.
AB  - To evaluate the effect of long-term exposure to heavy metals on skeletal muscle,
      chronic subcutaneous injections for 7 days of two level treatments (low dose, 0.1
      mg/kg and high dose, 1 mg/kg) of lead acetate were investigated. Comparative
      analyses of in situ dorsiflexor muscle isometric contractile characteristics were
      studied in urethane-anesthetized (2 mg/g, i.p.) control and lead-exposed male
      mice. Control muscle-twitch tension reached an average of 1.81 +/- 0.06 g.
      Chronic lead (Pb2+) treatments did not affect muscle contractile speed, but
      reduced significantly the twitch tension in both high and low doses when compared
      to control animals. This effect was in a dose-dependent manner; 1.21 +/- 0.07 g
      for low dose and 0.90 +/- 0.05 g for high dose. These chronic Pb2+ treatments
      accelerated muscle fatigue after 250 stimuli (25 Hz for 10 sec) in both the low
      and high doses equally. However, marked elevation in tetanic (25 Hz) specific
      tension were observed in the high-dose, chronically treated animals, indicating
      some changes in contractile apparatus function. The high dose of chronic Pb2+
      treatment induced ultrastructural changes, including reduced number of synaptic
      vesicles, disruption of mitochondria and increased number of smooth endoplasmic
      reticulum and myelin-like figures in the intramuscular axons and neuromuscular
      junctions. Chronic Pb2+ treatment caused extensive disruption of the sarcoplasmic
      mitochondria and increased the number of myelin-like figures in the muscle. These
      results suggest that exposure to Pb2+ at a low concentration can compromise the
      in situ skeletal muscle isometric contraction.

PMID- 8735789
TI  - Rationale and indications for continuous infusion of antihemophilic factor
      (factor VIII).
AB  - The continuous infusion of drugs and biological compounds, such as factor VIII
      concentrate, should enhance therapeutic efficacy. Factor VIII can be produced by
      recombinant DNA technology or derived from plasma. Improvements to the stability
      of the compound have made continuous infusion feasible. Current and potential
      applications of continuous infusion of factor VIII product include (1) peri
      operative conditions, (2) bleeding that threatens life or limb, (3) primary or
      secondary Prophylaxis and (4) immune tolerance therapy for factor VIII allo
      antibodies. Less use of costly factor VIII and decreased laboratory expenses also
      contribute to the usefulness of continuous infusion.

PMID- 8735788
TI  - Mechanisms of pattern generation in co-cultures of embryonic spinal cord and
      skeletal muscle.
AB  - Spontaneous output patterns of embryonic spinal cord slices in vitro were
      investigated in order to study the formation of pattern-generating networks.
      Patterns of spontaneous contractions of skeletal muscle fibers were recorded in
      co-cultures of embryonic rat spinal cord, dorsal root ganglia and skeletal
      muscle. A part of these contractions was shown to be driven by spinal circuits.
      These neuron-driven activity patterns changed from random to rhythmic when the
      inhibitory synapses in the spinal cord were blocked by strychnine, bicuculline or
      both. Rhythmic patterns consisted of bursts of activity (tetanic contractions)
      followed by periods of relaxation. The transition from random to rhythmic
      patterns occurred during a period of heavily increased rate of activity.
      Presynaptic inhibition was not involved critically in the generation of rhythmic
      patterns. Such patterns were, however, modulated through muscarinic and alpha
      adrenergic receptors. Neither NMDA nor glutamate nor its uptake blocker
      dihydrokainate induced rhythmic patterns of contraction, although NMDA in the
      presence of low magnesium increased moderately the rate of random activity. In
      order to study the size of pattern-generating networks, parts of the spinal cord
      slices were sectioned during rhythmic activity. Tangential cuts at the lateral or
      dorsal side of the slices reduced either the rate or the duration of the bursts
      or both. Sagittal cuts suppressed the activity almost totally. These findings
      suggest that the pattern generators in the slices consist of excitatory networks
      covering the entire slice, and that these networks reverberate following
      spontaneous activity of some distributed elements.

PMID- 8735790
TI  - Design and assessment of clinical trials on continuous infusion.
AB  - Continuous infusion of coagulation factors is becoming increasingly popular, and
      is mirrored by the accelerating rate of publications on this topic. However,
      several questions remain, particularly regarding efficacy. For this purpose, well
      designed trials are required. Some guidelines for such trials are presented here.

PMID- 8735791
TI  - Factor VIII pharmacokinetics: intermittent infusion versus continuous infusion.
AB  - During the last few years, the purity of clotting factor concentrates has
      increased, especially with the advent of products derived from recombinant DNA
      technology. Clearly, a standard technique is needed when evaluating the in vivo
      behavior of these new products in hemophiliacs. The general principles of
      pharmacokinetics have been applied to the study of clotting factor concentrates,
      and the most useful kinetic parameters have been defined according to single- or
      repeated-dose studies. A comparison between different schedules of treatment by
      repeated bolus infusions has indicated that the dose reduction at steady state is
      inversely related to the time interval between administration. When factor
      concentrate is delivered by continuous infusion, the time interval is zero and
      the saving is maximum. The advantages of continuous infusion are particularly
      evident in hemophiliacs undergoing surgery.

PMID- 8735792
TI  - Continuous infusion of factor VIII for surgery and major bleeding.
AB  - In a clinical trial, 24 patients with haemophilia A who needed surgery or had
      suffered severe bleeding were treated by continuous infusion of Monoclate P, a
      factor VIII concentrate that is immunopurified by monoclonal antibodies.
      Continuous infusion of Monoclate P began with a dose of 2 U/kg per h that was
      adjusted according to the results of factor VIII assays to achieve a factor VIII
      target level of 100 IU/dl for 2 days and then 80 IU/dl for 5 days. The safety,
      efficacy, and economics of this approach were assessed. No haemorrhagic episodes
      were observed. The continuous infusion was convenient and had the advantage of
      producing steady-state levels of factor VIII. With a single-compartment model, we
      found median factor VIII clearance values of 3.11 (range 1.79-7.78) x 10(3)
      litres/kg per h, elimination rates of 5.0-19.4 x 10(-2)/h and a median half-life
      of 9.9 h (range 4.8-20.0 h). Clearance and the elimination rate appeared to
      decline over the infusion period, as judged by the decreasing infusion rate
      required to maintain the target concentration of factor VIII. An economic
      comparison with bolus therapy, using theoretically derived bolus dosages,
      indicated that the potential saving was related inversely to the factor VIII half
      life. Potential savings of 75% were predicted on the first postoperative day,
      averaging 35% over the full course of therapy.

PMID- 8735793
TI  - Family issues in continuous infusion therapy with factor VIII.
AB  - Two recent advances in hemophilia therapy have led to clinical trials that
      incorporate more aggressive approaches to prevent bleeding complications. The
      production of factor VIII using recombinant DNA technology diminishes the risk of
      viral transmission in factor concentrate and thus increases safety. The
      administration of factor VIII by continuous infusion optimizes pharmacokinetics
      to achieve a sustained factor VIII level using the least number of units, and
      thus decreases cost. Providing factor concentrate by continuous infusion at home
      is very challenging to parents and children. Compliance can be supported by
      addressing issues that affect the family and its functioning. These issues
      include acceptance of the diagnosis, perception of the problem, parenting style,
      communication, social supports, disclosure issues, financial concerns, and
      perceived benefits and toxicities of the therapy plan. Health care providers must
      recognize and address these issues in order to provide adequate support for the
      family. Critical interventions include adequate time and optimal conditions for
      family education, support groups, determination of family expectations,
      understanding of parenting style, assistance with communication, disclosure,
      financial issues and clarification of the risks and benefits of various treatment
      plans.

PMID- 8735794
TI  - Review of pumps for continuous infusion of coagulation factor concentrates: what
      are the options?
AB  - Continuous infusion of coagulation factor concentrates has become more popular in
      recent years because it can substantially reduce the cost of surgery for a
      patient with hemophilia. This technique has also been used successfully for
      treatment of severe bleeds, induction of immune tolerance and short-term
      prophylaxis. The large selection of devices complicates the choice of an infusion
      system for this delivery approach. However, choosing the best type of device for
      a particular situation may determine the success or failure of continuous
      infusion.

PMID- 8735795
TI  - Prophylaxis and continuous infusion for hemophilia: can we afford it?
AB  - Little is known about the ideal factor regimen for hemophiliacs nor how treatment
      should be administered. A prospective multicenter study evaluated different
      dosage regimens and defined orthopedic outcomes, based on factor consumption and
      a comparison of prophylaxis with on-demand therapy. Prophylaxis led to better
      outcomes, whether joints were initially normal or previously affected. Factor use
      was substantially more costly if prophylaxis was used, but a major reduction
      could be achieved if continuous infusion were feasible.

PMID- 8735796
TI  - Central venous access catheters in children with haemophilia.
AB  - Twenty-five central venous lines (two external 23 subcutaneous ports) were placed
      in 19 boys with haemophilia A (n = 17) or B (n = 2). The mean age of the boys was
      4.9 years (range 0.2-15.3 years). The haemophilia was severe (factor level < 1%)
      in 18 boys and moderate (factor level 3%) in one. Three boys had circulating
      inhibitors and three were positive for human immunodeficiency virus (HIV)-1
      antibody. Central venous lines were placed to facilitate intermittent factor
      replacement therapy (n = 6), long-term factor prophylaxis (n = 9), induction of
      an immune tolerance protocol (n = 2) or therapy for acquired immunodeficiency
      syndrome (AIDS)-related complications (n = 2). The ports remained in place for
      15795 days (mean 687 days, range 11-2059 days). The frequency of port-related
      sepsis was 48% (11/23 ports in eight boys) or 0.7 port infections per 1000
      patient days. Ports were removed from five boys with an unresolved infection
      (four with Staphylococcus aureus sepsis and one with Pseudomonas sp. sepsis).
      Other complications requiring port removal included a catheter tip placed too
      high in the venous system (n = 1), severe persistent pain associated with needle
      access of the port (n = 1) and a subclavian vein thrombosis (n = 1). Both the
      benefits and risks of a subcutaneous port should be considered when deciding
      whether to place this device in a very young child with haemophilia.

PMID- 8735797
TI  - Bacteriology, safety and prevention of infection associated with continuous
      intravenous infusions.
AB  - There are over 50,000 intravascular catheter-associated bloodstream infections in
      the United States each year; globally, the number of these infections is likely
      to be much higher. At least half of these bloodstream infections are caused by
      staphylococci. The source of most pathogens causing endemic catheter-associated
      bloodstream infections is the catheter insertion site or the catheter hub,
      whereby microbes migrate into the bloodstream along the outside or inside of the
      catheter, respectively. The pathogenesis of epidemic intravascular catheter
      related bloodstream infections is quite different. Epidemic bloodstream
      infections are due to manufacturer-related contamination or contamination that
      occurs at the location of catheter use, such as the hospital. These epidemics
      have most often been traced to contamination of intravenous solutions such as
      hyperalimentation or medications, blood products, contaminated cutaneous
      antiseptics or faulty decontamination of reusable devices. The prevention of
      infection associated with continuous intravenous infusion of factor VIII poses a
      number of challenges. Assurances of the sterility of the product is of paramount
      importance, as is proper storage of the product prior to use. Prevention of
      infection will further require particular attention to the conditions surrounding
      insertion of the catheter, including the optimal site of insertion, maximal
      barrier precautions and optimal disinfection of the insertion sites, and also to
      conditions surrounding maintenance of the device after insertion, including
      proper disinfection and aseptic techniques when manipulating the catheter hub,
      daily assessment of the insertion site, and maintaining scheduled changes of the
      intravenous tubing. With proper precautions, the risk of serious infection
      associated with a continuous infusion of factor VIII should be minimal.

PMID- 8735798
TI  - Effects of poloxamer 407 on the assembly, structure and dissolution of fibrin
      clots.
AB  - Poloxamer 407 has shown clinical promise in suppressing surgically related
      adhesion formation. The mechanisms by which this occurs are not well understood.
      Since poloxamer 188 has rather dramatic fibrin altering properties, the present
      study was performed to evaluate the effects of poloxamer 407 on fibrin assembly,
      structure and dissolution. Studies were performed in platelet-rich plasma (PRP),
      platelet-poor plasma (PPP) and a purified protein system. Poloxamer 407 enhanced
      the rate of fibrin assembly, and increased final gel turbidity. As poloxamer 407
      concentration rose from 0 to 20 mg/ml in the purified protein system, the final
      gel optical density (OD) increased from 0.30 to 0.95, and fiber size (mass/length
      ratio [mu]) increased from 2.4 to 13.4 x 10(13) daltons/cm. Precipitation was
      noted in the purified system at poloxamer 407 concentrations > or = 20 mg/ml.
      Over a poloxamer 407 range of 0-20 mg/ml, mu increased from 2.64 to 13.2 x 10(13)
      daltons/cm in PRP. In PPP, mu increased from 2.95 to 9.25 x 10(13) daltons/cm. In
      contrast to results with poloxamer 188, clot lysis with tPA (43 IU/ml) was
      prolonged in the presence of poloxamer 407. At 20 mg of poloxamer 407 per ml,
      clot lysis was less than 18% complete after 3000 s. For the control, lysis was
      50% complete after 1350 s. Poloxamer 407 inhibition of fibrinolysis was due to
      inhibition of plasminogen activation or plasmin activity. The fibrin altering
      properties of poloxamer 407 may partially explain some of this agent's
      interesting clinical properties.

PMID- 8735799
TI  - Plasma factor VII levels are influenced by a polymorphism in the promoter region
      of the FVII gene.
AB  - Genetic factors play a role in determining the variability of plasma factor VII
      (FVII) levels in healthy individuals. There is also evidence that high serum
      lipids are associated with high FVII levels in plasma. In the promoter region of
      the human FVII a DNA polymorphism has been described, originating from a
      decanucleotide insert present in the less frequent allele. This biallelic system,
      reflecting the absence (AA) or presence (Aa) of the decanucleotide, can be
      detected by a DNA enzyme immunoassay of PCR products. We evaluated the
      association between the polymorphic alleles and the levels of FVII:Ag and FVII:C
      in 100 healthy individuals and in 19 hypertriglyceridemic individuals. Among
      healthy individuals, mean FVII:Ag and FVII:C levels of those with the homozygous
      genotype (A/A; mean FVII:Ag 112%, mean FVII:C 109%) were significantly higher (P
      < 0.001) than the mean levels of those with the heterozygous genotype (A/a, mean
      FVII:Ag 80%, mean FVII:C 90%; P < 0.001). Similar genotype-associated differences
      for FVII:Ag and FVII:C were found in individuals with triglycerides above 250
      mg/dl (P < 0.05). FVII:C and FVII:Ag levels were positively related to
      triglycerides only in individuals without the insert (P < 0.01); there was no
      significant relationship in those carrying the allele with the insert (A/a; P =
      0.43 and 0.08). Our findings of genotype-associated differences in FVII levels
      and interactions with triglycerides are similar to those obtained with the amino
      acid dimorphism at position 353 of the factor VII protein.

PMID- 8735800
TI  - Complex functional and structural coagulation abnormalities in the carbohydrate
      deficient glycoprotein syndrome type I.
AB  - Carbohydrate-deficient glycoprotein (CDG) syndrome type I is an autosomal
      recessive disease with multisystemic manifestations. During childhood the
      patients may suffer from hemorrhages, which may be lethal, venous thromboses and
      stroke-like episodes. In this study 15 patients with CDG syndrome type I were
      examined from the levels and isoform patterns of coagulation factors and
      inhibitors and fibrinolysis parameters. The screening assays APTT and PTC were
      unaffected in most cases. In spite of this reduced levels were found particularly
      for factors II, V, X and XI and for antithrombin and protein C. Low values tended
      to be associated with elevated liver enzyme levels in serum. The values were at
      potential clinical risk levels for protein C and/or antithrombin in more than
      half of the patients, and for factor V and/or factor XI in one third of them.
      There were no current differences in values between patients who had previously
      displayed clinical symptoms of coagulation disturbance and those without such
      symptoms. Partially carbohydrate-deficient isoforms were demonstrated in
      antithrombin, protein C, protein S and in alpha 2-antiplasmin, but not in factors
      II, X and fibrinogen. Abnormal isoforms did not appear to reduce the functional
      activity of the respective glycoproteins. Analysis of individual hemostatic
      parameters is recommended in these patients in connection with clinical symptoms
      or elective surgery. The observed variability of the carbohydrate defect in
      glycoproteins in this disease may be a clue to its pathogenesis.

PMID- 8735801
TI  - Serotonin stimulates megakaryocytopoiesis via the 5-HT2 receptor.
AB  - It is known that platelet alpha-granule constituents including platelet-derived
      growth factor (PDGF), platelet factor 4 (PF4) and transforming growth factor-beta
      (TGF-beta) can affect megakaryocytopoiesis. Serotonin, a platelet dense granule
      constituent has been shown to have a mitogenic effect on fibroblasts and smooth
      muscle cells but whether it has the same effect on megakaryocytes remains
      unclear. In this study, we investigated the effect of serotonin on
      megakaryocytopoiesis and the possible mechanism of its effect using the mouse
      plasma clot culture method. The results show that: (a) serotonin significantly
      stimulates megakaryocyte colony formation with maximum stimulation at 100 nM; (b)
      enhanced action is found between serotonin and interleukin-3 (IL-3), interleukin
      6 (IL-6), granulocyte macrophage-colony stimulating factor (GM-CSF),
      erythropoietin (EPO) and PDGF; (c) ketanserin, a 5-HT2 receptor antagonist,
      blocks the mitogenic effect of serotonin on megakaryocytopoiesis; and (d) Meg-01
      cells (a megakaryocyte cell line) express 5-HT2 receptors. This study
      demonstrates that serotonin has a mitogenic effect on megakaryocytopoiesis and
      this effect may be mediated via the 5-HT2 receptor which is known to be coupled
      to G protein. It is suggested that serotonin may also be involved in the feedback
      control of megakaryocytopoiesis.

PMID- 8735802
TI  - Recommendations for the treatment of factor VIII inhibitors: from the UK
      Haemophilia Centre Directors' Organisation Inhibitor Working Party.
AB  - A strategy is described for the initial detection, management and elimination of
      factor VIII inhibitors arising in patients with congenital and acquired
      haemophilia A. It is suggested that children with severe haemophilia A should be
      screened every 3 months up to the age of 10 years for inhibitors using the
      Bethesda method. Factor VIII inhibitors arising in these patients should be
      abolished using immune-tolerance induction wherever possible. Such regimes should
      be started as early as possible, preferably when the inhibitor titre is < 10
      Bethesda Units (BU)/ml, and should not be interrupted. High-intensity regimes are
      recommended for patients whose inhibitors exceed 10 BU. Autoantibodies to factor
      VIII giving rise to acquired haemophilia should be abolished using high-dose
      immunoglobulin or conventional immunosuppression. The choice of haemostatic agent
      for the treatment of severe bleeding should be based upon the clinical
      circumstances and the current inhibitor value, measured using both human and
      porcine factor VIII in the Bethesda assay. The past anamnestic response should
      also be considered when choosing treatment for minor bleeding episodes.

PMID- 8735803
TI  - Type I antithrombin deficiency: five novel mutations associated with thrombosis.
AB  - The genetic basis of Type I antithrombin deficiency has been investigated in six
      unrelated kindred with positive histories of thrombosis using a PCR
      amplification/direct sequencing approach. Four frameshift mutations, all
      introducing premature translation termination codons were identified. Thus,
      deletions, of a C at nucleotide position 2599 or 2600, a G at position 2601-2602
      and a CT dinucleotide at position 7428-7429 were detected in three kindred and
      confirmed by restriction enzyme analysis. The identical insertion, of a T at
      nucleotide 2770, was observed in two apparently unrelated families. This finding
      may have been due to a founder effect since antithrombin gene polymorphism
      analysis showed all affected individuals to share a common haplotype. An in frame
      deletion of 6 bp at nucleotide position 2690-2696 causing the removal of codons
      76 and 77 encoding Ile 76 and Phe 77 was also detected indicating that these
      amino acids are essential for stability of the mature antithrombin.

PMID- 8735804
TI  - Drawbacks of the MAIPA technique in characterising human antiplatelet antibodies.
AB  - Monoclonal Antibody-specific Immobilisation of Platelet Antigens (MAIPA) assays
      have been developed to allow the identification and characterisation of
      antibodies directed against platelets. A major disadvantage of the MAIPA test is
      the existence of false negative results. This is due to the competition between
      human and monoclonal antibodies (MoAb) for epitopes that are either identical or
      very close. In this report we used the MAIPA technique to test anti-HPA-1a
      alloantibodies and anti-Naka isoantibodies in conjunction with a panel of murine
      MoAbs directed against CD41/61 or CD36 respectively. Our data demonstrate that
      the choice of MoAbs used in MAIPA is very important for accurate diagnosis of
      clinical conditions and institution of specific therapy. Moreover, the results
      obtained are in favour of an heterogeneity for the recognition of the alloepitope
      HPA-1a and of distinguishable epitopes on GPIV.

PMID- 8735805
TI  - Signals elicited from human platelets by synthetic, triple helical, collagen-like
      peptides.
AB  - Synthetic collagen-like peptides, of general structure [Gly-Pro-HyP]n, adopt the
      triple-helical structure which is essential for the platelet-reactivity of native
      collagens. These peptides are potent activators of platelets, stimulating
      platelet aggregation at much lower dose than collagen fibres, but, unlike
      collagen fibres, they are not recognised by the integrin alpha 2 beta 1. We have
      examined the ability of the synthetic peptides to activate the various signalling
      pathways which regulate human platelet function. The peptides are potent
      activators of Ca2+ mobilisation and of protein kinase C, and they stimulate
      tyrosine phosphorylation of some substrates preferentially. However, in contrast
      with native type I collagen fibres, they are unable to inhibit platelet adenylate
      cyclase. This suggests a mode of action for the synthetic peptides which
      substantially overlaps, but which is not entirely identical with, that of native
      collagen.

PMID- 8735806
TI  - Dual effects of diclofenac on human platelet adhesion in vitro.
AB  - The effect of two non-steroidal anti-inflammatory drugs on the adhesion function
      of human platelets was evaluated. Platelets isolated from healthy human subjects
      were treated for 10 min with the indicated drugs and then incubated in fibrinogen
      coated microwell plates in the absence or in the presence of ADP (10 microM) and
      thrombin (0.05 U/ml). After 1 h of incubation, adherent platelets were measured
      using an enzymatic assay. ADP- and thrombin-stimulated adhesion was significantly
      inhibited by high doses ( > 500 microM) of diclofenac, while doses ranging from
      50 to 300 microM stimulated adhesion in the absence of agonists (resting
      platelets). A similar stimulatory effect on platelet adhesion was observed also
      with 200-500 microM flurbiprofen. Moreover, immunocytofluorimetry demonstrated
      that diclofenac dose-dependently (100-500 microM) induced the expression of GMP
      140 and increased the expression of GPIIb/IIIa on the membrane of unstimulated
      platelets. High doses ( > 500 microM) of this drug inhibited thrombin-stimulated
      expression of GPIIb/IIIa and GMP-140.

PMID- 8735807
TI  - Platelet size: measurement, physiology and vascular disease.
AB  - Platelet volume is a marker of platelet function and activation. It is readily
      measured as mean platelet volume (MPV) by clinical haematology analysers using
      sodium citrate as the anticoagulant. Measurement in EDTA can be unreliable since
      MPV increases significantly in a time-dependent manner. MPV correlates with
      platelet function and activation, whether measured as aggregation, thromboxane
      synthesis, beta-thromboglobulin release, procoagulant function, or adhesion
      molecule expression. MPV is increased in certain vascular risk factor states,
      including hypercholesterolaemia and diabetes mellitus, but not essential
      hypertension. It is increased in acute myocardial infarction, acute ischaemic
      stroke, pre-eclampsia and renal artery stenosis. Importantly, an elevated MPV
      predicts a poor outcome following myocardial infarction, restenosis following
      coronary angioplasty, and the development of pre-eclampsia. Research into the
      epidemiology of MPV is now required to determine whether thrombomegaly is a risk
      factor for developing vascular disease. Similarly, the physiological mechanisms
      which regulate MPV within the megakaryocyte need to be elucidated. Whether MPV
      ever becomes a routinely requested test remains to be seen but changes in
      methodology will be required first.

PMID- 8735808
TI  - Studies of the platelet filter test (shear dependent platelet aggregation) in
      patients with uncommon haemorrhagic disorders.
AB  - Platelets of anticoagulated whole blood forced at 40 mmHg through a fine filter
      are activated, aggregated and retained, so block the filter (platelet filter
      test, O'Brien JR, Salmon GP. Blood 1987; 1354-1361). Our clinical experiences
      with this simple and quick haemostasis test are summarized. Patients were
      investigated with different types of vWD (type-1 = 35, type-2A = 7, type-2B = 7,
      type-3 = 1), Glanzmann's thrombasthenia, congenital deficiency of cyclo
      oxygenase, acquired Bernard-Soulier syndrome, FXII-, FXIII-deficiency and a
      control group. The cumulative drop count and the platelet retention were
      carefully measured during two phases of the filter test. Platelet count, bleeding
      time, vWF:Ag and vWF:Rcof activity were measured along with the platelet filter
      test. The filter was not blocked and the platelet retention was abnormally low in
      all patients with thrombasthenia, type-2a, type-2B, type-3 vWD. Treatment with 1
      desamino-8-D-arginine-vasopressin (DDAVP) caused enhanced platelet retention in
      16 patients with type-1 vWD. The test is simple, quick and cheap, has good
      reproducibility, and may be useful in clinical haemostasis laboratories for
      examination of high shear induced platelet functions.

PMID- 8735809
TI  - Platelet surface activation antigen expression at baseline and during elective
      angioplasty in patients with mild to moderate coronary artery disease.
AB  - Platelet activation is an important pre-thrombotic event. The elucidation of its
      pathophysiology could contribute to a reduction in the mortality associated with
      coronary artery disease-the foremost cause of death in the UK. We examined the
      platelets of 27 patients with angiographically documented coronary artery
      disease. All patients had stable angina and were taking their regular medication
      including aspirin. We demonstrated significantly increased expression of GP53 and
      activated GPIIb/IIIa on the platelet surface using a sensitive flow cytometric
      method of detection. Comparison was made with a control group of 35 patients.
      Seventeen of the patients had coronary angioplasty carried out. Serial studies of
      these patients demonstrate an immediate and sustained increase in platelet
      activation and this has important implications for prevention of restenosis after
      angioplasty.

PMID- 8735810
TI  - Correlation of GP53 and P-selectin expression in myeloproliferative disorders and
      normal controls.
AB  - Platelet degranulation occurs when platelets are activated. Alpha degranulation
      releases P-selectin whereas lysosomal degranulation releases GP53. A correlation
      between these two markers might therefore be expected. We studied the correlation
      between P-selectin and GP53 in 50 patients with myeloproliferative disorders
      (MPD), 35 normal controls and 105 disease controls (patients with inflammatory
      bowel disease [IBD, n = 52], rheumatoid arthritis [RA, n = 26] and coronary
      artery disease [CAD, n = 27]) by flow cytometry before and after stimulation with
      thrombin ex vivo. There was no significant correlation between percentage
      expression of P-selectin and GP53 in unstimulated samples in normal individuals;
      r = 0.13, P = 0.3, n = 34. Mild thrombin stimulation (10 mU/ml) led to both alpha
      and lysosomal degranulation with a strong correlation (r = 0.62, P < 0.001, n =
      35). Disease controls (IBD, RA and CAD) showed similar trends. In patients with
      MPD, in contrast, a strong correlation between the expression of these platelet
      activation markers was demonstrable in unstimulated samples (r = 0.37, P = 0.007,
      n = 50). P-selection and GP53 expression in stimulated samples also correlated
      well. The data support the existence of different control pathways for the steady
      state expression of P-selection and GP53. Heterogeneous steady state responses of
      P-selectin and GP53 may be physiological and loss of this heterogeneity may be a
      hitherto unreported and pathologically important feature of MPD. This lack of
      correlation appears to be specific to MPD and is not simply a function of
      increased in vivo platelet activation.

PMID- 8735812
TI  - Activation of the endothelin B receptor causes a dose-dependent accumulation of
      cyclic GMP in human platelets.
AB  - Endothelins modulate in vitro aggregation of human platelets in a bi-directional
      manner. Thus endothelin-1 has been shown to act as a potentiator of primary
      aggregation and an inhibitor of secondary aggregation. The endothelin receptors
      and corresponding second messengers which cause these effects have not yet been
      characterised. This study investigated the effect of endothelin-1, an agonist at
      both the ETA and the ETB receptors and sarafotoxin (SRTX) S6c, a selective ETB
      agonist, on human platelet cyclic nucleotide levels. Neither endothelin-1 (10(
      11) -10(-7) M) nor SRTX S6c (10(-11) -10(-7) M) significantly altered platelet
      cAMP levels. In contrast, both agonists produced a dose-dependent increase in
      platelet cGMP. From these data, we conclude that activation of the ETB receptor
      in human platelets is responsible for an increase in platelet cGMP and may
      contribute to the inhibition of platelet aggregation caused by the endothelins.

PMID- 8735811
TI  - Immunoelectron microscopic changes of the platelet plasma membrane after
      activation.
AB  - The observation of protein redistributions from one compartment to another during
      platelet activation reflects changes in platelet functionality. At rest alpha
      granules express a high level of the main aggregation receptor GPIIb/IIIa, and
      only a small amount of the adhesion receptor complex GPIb/IX/V which lines the
      plasma membrane. After activation, the plasma membrane loses GPIb whereas the
      level of expression of the other aggregative proteins such as GPIIb/IIIa
      increase. These observations correlate well with the passage of the platelet from
      an adhesive to an aggregative state.

PMID- 8735813
TI  - Platelet activation during provocation of coronary artery spasm by ergonovine and
      cold pressor testing in patients with angina pectoris.
AB  - The role of coronary spasm in variant angina is well established. We have studied
      the time course of platelet activation during Ergonivine provocation to determine
      one significance of platelet indices for spasm testing. The results showed that
      spontaneous platelet aggregates and beta-thromboglobulin levels in patients with
      coronary vasospasm were increased during provocation and that platelet activation
      during a positive Ergonivine test precede ECG changes and chest pain.

PMID- 8735814
TI  - Expression, purification and characterisation of recombinant pallidipin, a novel
      platelet aggregation inhibitor from the haematophageous triatomine bug Triatoma
      pallidipennis.
AB  - Pallidipin is a platelet aggregation inhibitor protein originating from the
      saliva of the haematophageous triatomine bug Triatoma pallidipennis. Its
      inhibitory effects are specific for collagen-induced platelet aggregation. The
      recombinant form of the protein was expressed in the periplasmic space of
      transformed Escherichia coli using a vector based on the alkaline phosphatase
      gene promoter and leader peptide. Recombinant pallidipin was purified in three
      chromatographic steps including cation exchange, anion exchange and size
      exclusion gel chromatography. SDS/PAGE and N-terminal amino acid sequencing
      showed that recombinant pallidipin had a molecular weight similar to that of the
      salivary protein (approximately 19 kDa) and had been correctly processed. The
      yield was 864 micrograms of pure protein from one litre of bacterial culture. The
      biological activity of recombinant pallidipin was assessed in a platelet
      aggregation assay using collagen at a concentration of 2 micrograms/ml as
      inducer, and the IC50 found to be 33 nM, similar to that determined for the
      native protein. When the collagen concentration used for induction was increased,
      higher pallidipin concentrations were also needed to achieve a comparable
      inhibition of platelet aggregation.

PMID- 8735815
TI  - Dose-responses to inducers and inhibitors of platelet aggregation analysed via a
      micro-method.
AB  - The ex vivo study of platelet function in small experimental animals treated with
      anti-platelet drugs is restricted by the limited availability of platelet-rich
      plasma (PRP). To circumvent this obstacle, a micro-method for platelet
      aggregation was developed that enables ED50 measurements for various inducers of
      platelet aggregation. Fifty microliters of human, hamster, or rabbit PRP was
      mixed with agonist in each well of a microtiter plate, and shaken at 900 rpm at
      37 degrees C for intervals up to 5 min. After stopping the aggregation with
      formaldehyde in PBS, light scattering was measured vs platelet-poor plasma (PPP)
      at 620 nm. Thus, aggregation in human PRP by ADP (t = 2 min) occurred with an
      ED50 = 1.8 microM, whereas the collagen (t = 3 min; ED50 = 2 micrograms/ml) and
      AA (t = 1 min; ED50 = 0.3 microM) induced aggregation occurred at those
      concentrations that induce aggregation in classical aggregometry. Likewise,
      aggregation was inhibited by the anti-GPIIb/IIIa antibody MA-16N7C2 and by the
      GPIIb/IIIa antagonists G4120 or MK-852. In comparison with human PRP, hamster
      (ED50 = 0.8 microM at t = 2 min) and rabbit (ED50 = 5 microM at t = 4 min)
      platelet aggregation by ADP occurred with comparable sensitivities, whereas the
      aggregation of rabbit platelets by collagen (ED50 = 15 micrograms/ml at t = 3
      min) appeared to be slightly less sensitive and subject to large interindividual
      variations. The method was applied to measure plasma levels of a GPIIb/IIIa
      antagonist following injection into hamsters.

PMID- 8735816
TI  - Inhibition of blood platelet functions by cationic amphiphilic drugs in relation
      to their physico-chemical properties.
AB  - The effects of bromadryl, dithiaden, chloroquine and propranolol on thrombin
      stimulated rat platelet aggregation (measured turbidimetrically) and thromboxane
      B2 generation (detected by an RIA method) were compared with four selected
      physico-chemical parameters of these drugs. Platelet aggregation was inhibited in
      the rank order of potency: bromadryl > dithiaden > propranolol > chloroquine,
      which corresponded with the decrease in the net charge of the terminal methyl-(or
      ethyl-) groups in the side chain and with the increase of the dipole moment of
      drug molecules. On the other hand, the rank order of potency in which the drugs
      tested inhibited thromboxane B2 formation (chloroquine > dithiaden > bromadryl >
      propranolol) correlated well with the decline in molar refractivity of the drugs.
      No relationship was found between inhibitory effects of drugs and their partition
      coefficients. The results presented indicate that inhibition of platelet
      functions might consist of several types of drug-cell interactions, depend on the
      structure and physico-chemical properties of the drugs and cannot be estimated
      simply on the basis of partition coefficients.

PMID- 8735818
TI  - Analysis of effects of adrenaline and collagen on the activity of prostaglandin
      E1-stimulated human platelet adenylyl cyclase.
AB  - A mathematical model relating the activity of adenylyl cyclase (AC) with
      concentrations of inhibitors, equilibrium dissociation constants, specific
      activity and efficacies of AC depending on the states of binding sites of the
      receptors was used for analysis of the data on inhibition of PGE1-stimulated AC
      of human platelet membranes (Farndale et al. Biochem J 1992; 282; 25-32). The
      equilibrium dissociation constant, x2 characterizing the affinity of adrenaline
      for its receptor, was estimated to be 0.14 microM; this constant is a better
      characteristic of adrenaline's potency than IC50, the concentration corresponding
      to half-asymptotic inhibition of AC. Collagen does not affect the affinity of
      adrenaline for its receptor. G protein involved in inhibition of AC activity by
      collagen is different from Gi2 mediating inhibition by alpha 2-adrenergic
      agonists. The model applied for the analysis may be thought to be the best means
      presently to relate dose-response dependencies to what is known or can be
      hypothesized about the mechanisms underlying inhibition of AC activity.

PMID- 8735817
TI  - Platelet-activating factor and not thromboxane A2 is an important mediator of
      endotoxin-induced platelet aggregation in equine heparinised whole blood in
      vitro.
AB  - Endotoxin has previously been shown to induce platelet aggregation in equine
      heparinised whole blood. This study aimed to determine whether platelet
      activating factor or products of cyclo-oxygenase metabolism (thromboxane A2 or
      prostaglandins) were important in mediating the response of platelets to
      endotoxin. The effects of the following drugs on endotoxin-induced aggregation
      were investigated: aspirin, flunixin meglumine and carprofen (non-steroidal anti
      inflammatory drugs); CV-3988 and WEB2086 (platelet-activating factor receptor
      antagonists); quinacrine (phospholipase A2 inhibitor). The effects of quinacrine
      on platelet aggregation in citrated platelet-rich plasma induced by ADP and
      platelet-activating factor were also investigated. CV-3988 and WEB2086 caused a
      concentration-dependent inhibition of endotoxin-induced aggregation. The non
      steroidal anti-inflammatories were without effect except flunixin meglumine which
      produced a small inhibition of endotoxin-induced aggregation. Quinacrine had a
      similar effect to the platelet-activating factor antagonists, but also non
      competitively inhibited platelet aggregation in citrated platelet-rich plasma. It
      is concluded that platelet-activating factor is a critical mediator of endotoxin
      induced platelet aggregation in the horse, but that products of cyclo-oxygenase
      metabolism are not of importance.

PMID- 8735819
TI  - Thrombospondin measured in whole blood--an indicator of platelet activation.
AB  - Abnormal platelet activation may be involved in prethrombotic states and lead to
      thromboembolism. When platelets become activated, they release thrombospondin
      (TSP) from their alpha-granules which binds mainly to the surface of activated
      platelets, platelet-derived microparticles and other blood cells. To determine
      bound as well as free TSP in a single assay, we developed an indirect ELISA to
      measure TSP in fixed whole blood. The intra-assay variance was less than 5% and
      97% of purified standard TSP, added to whole blood samples, was recovered with
      the ELISA. Blood collected with a 20G needle into a syringe resulted in lower
      "whole blood TSP' values than blood collected with the Vacutainer system. Whole
      blood TSP levels were measured in 66 healthy blood donors (20F, 46M) aged 25-75
      years. The mean whole blood TSP concentration was 33 +/- 19 ng/ml. No significant
      difference in whole blood TSP was found between healthy females and males (35 +/-
      23 ng/ml vs. 33 +/- 17 ng/ml).

PMID- 8735820
TI  - In vitro study of the anti-aggregating activity of two nitroderivatives of
      acetylsalicylic acid.
AB  - The antiplatelet activity of two new nitrocompounds, chemically related to
      acetylsalicylic acid (NCX 4215 and NCX 4016), was studied in vitro to verify the
      hypothetical dual action of these drugs. Both drugs, in a dose-dependent way,
      inhibited arachidonic acid-induced platelet aggregation and thromboxane A2
      production, measured as thromboxane B2 concentration in whole blood. These
      effects are likely to be related to cyclo-oxygenase inhibition. NCX 4215 and NCX
      4016 in a dose-dependent way inhibited also thrombin-induced aggregation of
      platelets pretreated with acetylsalicylic acid. These inhibitory effects are
      related to nitric oxide release and cGMP increase and significantly reversed by
      oxyhaemoglobin and methylene blue. Either as a cyclo-oxygenase inhibitor or as a
      nitric oxide donor, NCX 4016 proved to be significantly more potent than NCX
      4215.

PMID- 8735821
TI  - Contact-induced modulation of neutrophil elastase secretion and phagocytic
      activity by platelets.
AB  - It has been reported that platelets stimulate generation of reactive oxygen
      species in neutrophils and monocytes by a mechanism that requires mutual cell
      cell contact and the presence of P-selectin on the platelet surface. In the
      present study we investigated the effect of platelet-neutrophil contacts on
      neutrophil elastase secretion and phagocytic activity. Non-activated or thrombin
      activated platelets were fixed with formaldehyde, washed and incubated with
      neutrophils in the absence or presence of various neutrophil agonists. Elastase
      secretion was determined by measuring the enzyme activity in cell-free
      supernatants using a chromogenic substrate. Platelet-neutrophil adhesion and
      ingestion of zymosan particles by neutrophils were quantitated by light
      microscopy. Platelets significantly reduced elastase secretion from neutrophils
      but had no effect on the elastase activity in the supernatant of neutrophil
      lysates. When neutrophils were stimulated with the ionophore A23187 or the
      chemotactic peptide FMLP, thrombin-activated platelets were more potent to
      inhibit elastase secretion when compared with non-activated platelets.
      Neutrophils that were not able to bind platelets to their surface had a
      significantly lower phagocytic activity when compared with neutrophil with
      adherent platelets or neutrophils that were incubated in the absence of
      platelets. The results indicate that platelet-neutrophil contacts may also lead
      to an inhibition of neutrophil functions and that such inhibition could be due to
      a transient contact rather than due to a firm platelet-neutrophil adhesion.

PMID- 8735822
TI  - Redistribution of membrane glycoproteins in platelets activated under flow
      conditions.
AB  - A reduction in the ability of GPIb to bind specific MoAbs or ligands (vWF) has
      been reported in platelets exposed to thrombin in suspension. We have analyzed
      modifications in the presence of glycoproteins (GPs) on platelets activated under
      flow conditions in a system which allows limited thrombin and fibrin generation.
      Normal blood anticoagulated with low molecular weight heparin (LMWH, Dalteparin
      20 IU/ml) was recirculated for up to 10 min at 800 s-1 through annular chambers
      containing denuded arterial segments. Aliquots of blood were removed from the
      reservoir at 0, 1, 5 and 10 min and immediately mixed with paraformaldehyde.
      Membrane glycoproteins: GPIb (CD42b), GPIIb-IIIa (CD41a), GPIV (CD36); and
      activation dependent antigens: P-selectin (CD62P) and lysosomal glycoprortein
      (CD63), were detected in whole blood by dual color flow cytometry. Circulation of
      through the perfusion system resulted in platelet activated as demonstrated by
      the increased percentage of platelets positive for antigens CD62P and CD63. A
      gradual increase in the binding of MoAbs directed against GPIb, GPIIb-IIIa, and
      GPIV epitopes was noted during the entire perfusion period. Observed differences
      in mean fluorescence intensities at all the observation times were statistically
      significant (P < 0.001). Our results obtained on platelets in an experimental
      thrombosis system indicate that GPIb, GPIIb-IIIa and GPIV remain on the surface
      of activated platelets and actually increase their expression. Alterations
      detected at the level of GPIb in platelets activated by thrombin in suspension
      may not take place under in vivo situations.

PMID- 8735823
TI  - Activated platelets and impaired platelet function in intensive care patients
      analyzed by flow cytometry.
AB  - Intensive care patients often have disturbances in their coagulation and
      fibrinolysis systems, which may result in haemorrhage or disseminated
      intravascular coagulation (DIC). DIC is a dreaded complication that may develop
      rapidly and has a high mortality rate. Platelets play a central role in
      haemostasis and it is thus important to have assays that rapidly can monitor
      platelet activation and platelet function. We have used flow cytometry to measure
      platelet activation and function in intensive care patients. Fluorescein labelled
      chicken antibodies were used to detect platelet bound fibrinogen as these
      antibodies have advantages over mammalian antibodies in flow cytometry. We found
      increased levels of circulating activated platelets and microparticles in vivo
      and impaired platelet function after stimulation in vitro. The two patients with
      the highest percentage of microparticles died shortly after blood sampling.

PMID- 8735824
TI  - Changes in the composition of the platelet cytoskeleton in response to ADP:
      effects of MK-852 and ARL 66096.
AB  - Platelet activation by adenosine diphosphate (ADP) results in an alteration in
      the composition of the cytoskeleton. Here we have determined the effects of MK
      852 and ARL 66096 on the cytoskeletal changes that occur. MK-852 is a GPIIb/IIIa
      antagonist that inhibits aggregation by interfering with fibrinogen binding ARL
      66096 is a P2T antagonist that selectively inhibits ADP-induced aggregation.
      Neither agent inhibits the shape change response. Experiments were performed in
      hirudinized platelet-rich plasma. Platelet activation led to a significant and
      sustained increase in the cytoskeletal content of actin binding protein (ABP),
      myosin, alpha-actinin, a 66K protein and actin, and a significant decrease in a
      31K protein. In the presence of MK-852 there was no increase in ABP or the 66K
      protein and no decrease in the 31K protein. The increase in myosin and alpha
      actinin became reversible but there was still incorporation of actin into the
      cytoskeleton. In the presence of ARL 66096 there was no increase in ABP or the
      66K protein and no decrease in the 31K protein. ARL 66096 also prevented
      incorporation of alpha-actinin and actin. As with MK-852, myosin incorporation
      became reversible. The results suggest that (1) myosin is incorporated into the
      cytoskeleton transiently during shape change, (2) ADP interaction with the ADP
      aggregation receptor (but not that for shape change) is associated with alpha
      actinin and actin incorporation into the cytoskeleton, and (3) further changes
      that occur are consequent to fibrinogen binding and platelet aggregation.

PMID- 8735825
TI  - Platelet aggregation in patients with primary pulmonary hypertension.
AB  - Platelet aggregation activity was investigated in patients with primary pulmonary
      hypertension in different stages of the disease. Platelets were activated with
      ADP and PAF. Spontaneous platelet aggregation was also measured. Spontaneous and
      low dose PAF-induced platelet aggregation in patients was greater than in healthy
      subjects and increased with the severity of the disease. It was concluded that
      the increased platelet activity can be related to unfavourable prognosis in these
      patients.

PMID- 8735826
TI  - High shear-induced platelet activation and inactivation: the importance of
      methodology.
AB  - High shear platelet activation may be conveniently studied by forcing blood
      through a fine filter in the filterometer. To achieve haemostasis in vivo
      platelets are activated. When haemostasis is achieved, inactivation must follow.
      In the filterometer, activation occurs with filter blocking (first phase) and
      after 100s inactivation ('rebleeding') may occur (second phase). We report the
      effect of different pressures, temperatures, incubation times, anticoagulants and
      aspirin in this system. Most 'rebleeding' occurred in citrate, followed by native
      blood, r-hirudin and low-molecular-weight heparin. Unfractionated heparin
      inhibited 'rebleeding' whereas aspirin potentiated it. These and other findings
      are technically and clinically relevant and contribute to an understanding of the
      mechanisms involved in 'rebleeding' and hence perhaps in thrombogenesis.

PMID- 8735827
TI  - A deletion in the alpha subunit locks platelet integrin alpha IIb beta 3 into a
      high affinity state.
AB  - The integrin alpha IIb beta 3 (GPIIb/IIIa) mediates platelet aggregation by a
      change in affinity for the ligand fibrinogen. The amino acids 991-995 (GFFKR) at
      the NH2-terminus of the cytoplasmic domain are highly conserved in all known
      integrin alpha subunits. We postulated that the GFFKR-region is important for the
      inside-out signal transduction and has an influence on the affinity state of
      integrins. To test this hypothesis, a mutant with a deletion in the GFFKR region
      was designed. The DNA-constructs were constructed by PCR, sequenced,
      cotransfected with the beta 3 subunit into CHO cells and cell surface expression
      was proven with immunoprecipitation and flow cytometry. The GFFKR-deletion mutant
      demonstrated a high affinity binding of the mAb PAC-1 and I125-labeled
      fibrinogen. The metabolic inhibitors 2-deoxyglucose and NaN3 did not change the
      affinity state of the deleted receptor. Neither did the truncation of the
      cytoplasmic domain of the beta 3 subunit. Additionally, expression of the deleted
      integrin in the erythropoetic cell line K562 revealed a high affinity state. A
      deletion of the GFFKR-region in the cytoplasmic domain of the alpha subunit locks
      integrin alpha IIb beta 3 in a high affinity state. This is an intrinsic property
      of the deleted receptor since there is no energy dependence and no cell type
      specifity. Thus, the GFFKR-region is involved in inside-out signaling in alpha
      IIb beta 3. Furthermore, cell lines expressing this activated alpha IIb beta 3
      integrin may be used as models for activated platelets.

PMID- 8735828
TI  - Thrombospondin peptides inhibit the secretion-dependent phase of platelet
      aggregation.
AB  - Thrombospondin (TSP) is a platelet alpha-granule adhesive glycoprotein (M(r) =
      450,000) that is released in large amounts from activated platelets and
      participates in thrombus formation. The aim of the present study was to assess
      the effect of peptides corresponding to sequences within the NH2-terminal region
      and type 1 repeats of TSP on platelet aggregation induced by thrombin in washed
      platelet suspensions. We found that TSP18 (amino acids 1-174), used at micromolar
      concentrations, inhibited platelet aggregation by 30-50%, reducing the size of
      the aggregates formed. Similar results were obtained with the hexapeptide Cys-Ser
      Val-Thr-Cys-Gly (amino acids 429-434 and 486-491) used at 1.2 mM. The shorter
      peptide Val-Thr-Cys-Gly was even more inhibitory whereas the peptide Val-Thr-Lys
      Gly, which lacks a cysteine, had no effect. Interestingly, we have constantly
      found that inhibition of platelet aggregation by these peptides was accompanied
      by an inhibition of alpha and dense granule secretion, suggesting that the
      binding of secreted TSP to the plasma membrane may participate in the platelet
      signaling process. We conclude that peptides of TSP may prove useful in the
      treatment of thrombosis by impairing both the release of proaggregating
      substances and platelet macroaggregate formation.

PMID- 8735829
TI  - Magnesium inhibits human platelets.
AB  - Magnesium (Mg) may inhibit experimental arterial thrombus formation by inhibition
      of platelet activity. However, inhibition of platelet aggregation has mainly been
      shown with high concentrations of magnesium ( > 2 mM). To test the effects of Mg
      in more clinically relevant concentrations, an in vitro study was performed where
      platelets were incubated with MgSO4 in the concentration range of 0.5-8.0 mM.
      Healthy volunteers participated on 2 consecutive days. On Day 2 the volunteers
      ingested 300 mg of acetylsalicylic acid (ASA) 1 h before blood sampling. Blood
      was anticoagulated with hirudin and platelet aggregation was performed in
      platelet-rich plasma (PRP) after incubation with saline or MgSO4 for 5 min.
      Platelets were stimulated with threshold concentrations of collagen or ADP or a
      fixed high concentration of collagen (5 micrograms/ml) on both days. A
      concentration dependent inhibition of platelet aggregation was found after
      addition of MgSO4. A statistically significant inhibition (P < 0.05) was present
      at 0.5-1.0 mM MgSO4. The effect of Mg was independent of pretreatment with ASA.
      Following maximal stimulation with collagen in PRP, a synergistic inhibition of
      ASA and Mg on platelet aggregation was demonstrated. Administration of MgSO4 in
      clinically relevant concentrations showed a dose-dependent inhibition of platelet
      aggregation. Platelet inhibition also occurred after ASA administration and
      concomitant medication induced a synergistic effect.

PMID- 8735830
TI  - Studies on the effects of agonists and antagonists on platelet shape change and
      platelet aggregation in whole blood.
AB  - The shape change that occurs when platelets are stimulated with an agonist can be
      quantitated by monitoring changes in their forward-scatter/side-scatter profile
      using a flow cytometer. Here we have stimulated platelets in citrated whole blood
      with several agonists and determined the time-course and extent of the shape
      change that occurs. In some experiments parallel investigations of shape change
      and aggregation were performed. Aggregation was measured by monitoring the fall
      in number of single platelets using a Whole Blood Platelet Counter. Some agents
      (ADP, PAF, U46619 and 5HT) produced a strong and rapid change in platelet forward
      scatter/side-scatter that was maximal within 10 s. Others (A23187 and collagen)
      produced a strong but slower response. Adrenaline produced only a weak response
      that was also slow to develop, and PMA did not produce any response. The
      concentrations of each of ADP, PAF, U46619 and 5HT needed to induce a shape
      change were lower than those required for aggregation. Selective PAF, TXA2 and
      5HT antagonists (WEB 2086, sulotroban and MCI-9042) clearly inhibited both the
      shape change and the aggregation induced by the appropriate agonist; in each case
      the effect of the antagonist was to move the dose-response curve to the right.
      These results are consistent with the shape change and aggregation brought about
      by each of these agonists being mediated via a single receptor. In contrast, a
      selective P2T purinoceptor antagonist (ARL 66096) markedly inhibited the
      aggregation induced by ADP but was found to have little or no effect on shape
      change. This is consistent with these platelet responses to ADP being mediated by
      different receptors, with P2T receptors mediating only the aggregation response.

PMID- 8735831
TI  - cAMP is not an important messenger for ADP-induced platelet aggregation.
AB  - In rat platelets, basal cAMP level did not vary significantly during ADP-induced
      aggregation. In the same conditions, no variation in the cAMP content was
      observed in platelets from rats treated with clopidogrel, whereas ADP-induced
      aggregation was totally inhibited. ADP decreased cAMP level in control
      prostacyclin- or forskolin-stimulated platelets whereas, in treated platelets,
      adenylyl cyclase down-regulation was strongly inhibited. SQ 22536 (500 microM),
      an inhibitor of adenylyl cyclase, strongly reduced the cAMP content of both
      control and treated platelets but did not reverse the anti-aggregating activity
      of clopidogrel, showing that inhibition of ADP-induced adenylyl cyclase down
      regulation in treated platelets was not responsible for the anti-aggregating
      effect of clopidogrel. Similar results were obtained in rabbit platelets. These
      results therefore demonstrate that cAMP is not an important second messenger for
      ADP-induced platelet aggregation and suggest that another activating pathway,
      linked to the low affinity ADP receptor present on the platelet surface might be
      involved in the aggregation process.

PMID- 8735832
TI  - Activation of human platelets by lysophosphatidic acid.
AB  - The biochemical mechanisms of platelet activation by lysophosphatidic acid were
      investigated. Lysophosphatidic acid interacts with a membrane receptor coupled to
      the inhibitory GTP-binding protein Gi and produces a rapid decrease of the
      intracellular concentration of cAMP. Aggregation of gel-filtered platelets by
      lysophosphatidic acid requires the presence of extracellular CaCl2, as this
      phospholipid does not induce secretion of platelet dense granules. Platelet
      activation by lysophosphatidic acid in the absence of extracellular CaCl2 does
      not involve phospholipase C activation, as evaluated by measuring mobilization of
      Ca2+ from internal stores and pleckstrin phosphorylation, but causes the rapid
      tyrosine phosphorylation of several intracellular proteins. Our results indicate
      that activation of intracellular tyrosine kinases is not secondary to Ca2+
      mobilization and protein kinase C activation in lysophosphatidic acid-stimulated
      platelets.

PMID- 8735833
TI  - New pentamidine related substances which simultaneously inhibit platelet
      aggregation and accelerate plasmin generation and in vitro clot lysis.
AB  - Pentamidine, a highly toxic drug, possesses RGD-peptide (Arg-Gly-Asp)-like
      antiplatelet actions. The objective of this investigation was to study the
      anticipated profibrinolytic and antiplatelet actions of pentamidine and of
      pentamidine (bearing guanidino-like groups)-related synthetic peptidomimetic
      compounds. Platelet aggregation inhibition was assessed using ADP, thrombin,
      collagen, arachidonic acid and epinephrine as inducers, by aggregometry. In vitro
      chromogenic plasmin generation tests and clot lysis assays were also performed.
      Two (assigned as D-2 and D-3) of the synthetic pentamidine-guanidino related
      molecules were able to inhibit platelet aggregation and simultaneously accelerate
      in vitro plasmin generation and clot-lysis in the nM range. These dual action
      antithrombotic agents now need to be tested further to assess their
      antithrombotic actions in vivo.

PMID- 8735834
TI  - Platelet aggregation, sensitivity to prostaglandin E1 and thromboxane A2 release
      in recombinant hirudin- and heparin-anticoagulated blood.
AB  - Hirudin is the most potent known natural inhibitor of thrombin and is presently
      gaining popularity as an anticoagulant since recombinant forms have become
      available. The aim of the present study was to compare platelet aggregation,
      sensitivity to prostaglandin E1 and thromboxane A2 release in r-hirudinized and
      heparinized blood. Platelet aggregation was measured turbidimetrically using a
      dual channel aggregometer (Labor, Germany) in blood samples of healthy volunteers
      anticoagulated with r-hirudin W015 (Behring) and heparin (20 micrograms/ml blood
      each). Aggregation was induced by arachidonic acid (0.5, 1.0 and 2.0 mM) and
      adenosine diphosphate (1.0 microM). Prostaglandin E1 in concentrations 10, 20, 40
      and 80 ng/ml was used. Plasma thromboxane B2 content was measured by gas
      chromatography/mass spectrometry. This study showed a significantly lower
      arachidonic acid induced platelet aggregation in r-hirudinized plasma. Three
      minutes after the aggregation induction by 0.5 mM arachidonic acid the plasma
      thromboxane B2 concentration was 23.0 ng/ml in blood anticoagulated with r
      hirudin and 108.4 ng/ml in heparin-anticoagulated blood. The extent of the
      aggregation induced by adenosine diphosphate was nearly the same in hirudinized
      and heparinized plasma. Platelet sensitivity to prostaglandin E1 was
      significantly higher in r-hirudinized blood. Thus, platelet aggregation induced
      by arachidonic acid is significantly lower and sensitivity to prostaglandin E1
      higher in r-hirudin-anticoagulated blood in comparison with heparin
      anticoagulated blood.

PMID- 8735835
TI  - Fate of the GPIb/IX receptor complex following activation of human platelets.
AB  - Many excellent workers have concluded that platelet glycoprotein Ib/IX complex,
      the receptor for von Willebrand factor (vWF) is down-regulated in its ability to
      bind vWF or monoclonal antibodies and virtually cleared from the exterior surface
      to internal membranes following exposure of the cells to thrombin in suspension.
      Studies carried out in our laboratory, however, have not supported the concept of
      down-regulation or clearance. Experiments employing aggregation-disaggregation
      reaggregation, agglutination and flow cytometry have demonstrated that
      physiologic levels of calcium ions prevent or reverse the phenomenon of down
      regulation. GPIb/IX receptors remain edge to edge on surface-activated platelets,
      whether or not the cells are also exposed to thrombin before or after spreading.
      Addition of two ligands, fibrinogen labeled gold to mark GPIIb/IIIa and vWF to
      identify GPIb/IX, to discoid platelets before surface activation demonstrates
      that GPIIb/IIIa is a mobile receptor that concentrates with its ligand in cell
      centers while vWF bound to GPIb/IX moves with the membrane as it expands to the
      lateral edges of spread cell margins. Immunogold studies of thrombin-activated
      platelets in suspension reveal no clearance of GPIb/IX receptors, bound or not to
      vWF, from exposed surfaces to internal membranes. The clearance to the OCS
      reported by others may be due to difficulties encountered in staining GPIb/IX
      lining OCS channels in resting discoid platelets.

PMID- 8735836
TI  - ADP-induced P-selectin expression on platelets as a predictor of successful
      thrombolysis.
AB  - Unlike coronary thrombolysis, the role of platelet activity in the outcome of
      local thrombolytic therapy for peripheral ischaemia is not well understood. In
      the present study ten patients undergoing local pulse spray thrombolysis (PST)
      with recombinant tissue-type plasminogen activator (rt-PA), six patients
      undergoing conventional infusion thrombolysis (CT) with rt-PA and another six
      patients undergoing arteriography with iopamidol were studied. Venous blood
      samples obtained before and after the procedure were analysed using a flow
      cytometric technique for detection of platelet activation after labelling
      platelets with VH10, a monoclonal antibody against P-selectin. In the present
      study no significant differences were observed in P-selectin expression before
      and after any of the procedures, except that P-selectin expression following ADP
      stimulation was reduced in patients who had received conventional thrombolysis.
      Unexpectedly, we observed relatively greater P-selectin expression, particularly
      after ADP stimulation, both before and following thrombolysis in ten patients in
      whom thrombolysis was successful compared with six patients in whom thrombolysis
      was unsuccessful. ADP-induced P-selectin expression on platelets may therefore be
      a useful predictor of outcome of peripheral intra-arterial thrombolysis.

PMID- 8735837
TI  - Role of lipoproteins in platelet activation.
AB  - Native low density lipoprotein influences platelets principally in a time- and
      dose-dependent manner. Oxidized low density lipoprotein activates platelets and
      promotes platelet adhesion. Certain parts of high density lipoprotein may
      decrease the risk of platelet activation. The calcium signaling pathway, protein
      kinase C pathway, and cytotoxic effect are probably involved in the platelet
      activation process.

PMID- 8735838
TI  - New drugs--reports of new drugs recently approved by the FDA. Dirithromycin.
AB  - Dirithromycin is a semisynthetic derivative of erythromycin, a 14-membered ring
      macrolide antibiotic. The drug is converted during absorption and distribution,
      to an active metabolite 9-(S)-erythromycylamine, which is the predominant
      compound found in plasma and extravascular tissues. High tissue concentration of
      erythromycylamine is achieved after oral doses of dirithromycin, with slow
      release back into the circulation. The mechanism of action of dirithromycin is
      like that of erythromycin and other macrolides. These compounds inhibit RNA
      dependent protein synthesis. It has recently been suggested that all macrolides
      stimulate dissociation of peptidyl-tRNA from ribosomes during the elongation
      phase, leading to inhibited protein synthesis. The antimicrobial spectrum of
      dirithromycin is similar to that of erythromycin, although the drug offers no
      significant advantage with regard to MIC values. In vitro against Gram-positive
      isolates, dirithromycin exhibits similar potency to that of clarithromycin,
      erythromycin, roxithromycin, and clindamycin. In vivo, dirithromycin is active
      against penicillin-susceptible Staphylococcus aureus, beta-hemolytic
      streptococci, and Streptococcus pneumoniae. Dirithromycin is as effective as
      penicillin VK against streptococcal pharyngitis and tonsilitis, and as effective
      as erythromycin against acute superimposed chronic bronchitis and skin and soft
      tissue infections. In comparison with other newer macrolides, dirithromycin has
      shown similar or lesser in vitro activity. In particular, Haemophilus influenzae,
      Bacteroides spp., Peptococcus-Peptostreprococcus spp., Clostridium perfringens,
      Legionella spp., Neisseria gonorrhoeae, and Chlamydia trachomatis were all less
      sensitive to dirithromycin than azithromycin or clarithromycin. Once-daily oral
      administration of dirithromycin (500 mg) has been demonstrated to be similar in
      efficacy to erythromycin (250 mg, 4 times daily), each for approximately 7 days,
      in the treatment of acute bronchitis or acute-exacerbations of chronic bronchitis
      in controlled studies. Proven or presumed pathogen eradication rates were 83 and
      86% for acute bronchitis patients treated with dirithromycin and erythromycin,
      respectively. Corresponding bacteriological response rates in acute exacerbations
      of chronic bronchitis were 75 to 84% with dirithromycin and 75 to 82% with
      erythromycin. Both agents achieved clinical cure or improvement in over 85% of
      the patients with either condition. The main advantage of dirithromycin over
      erythromycin appears to be once-daily administration. Lilly launched
      dirithromycin in September 1993, in Spain, received approval from FDA in August
      1995, and launched it during October 1995.

PMID- 8735839
TI  - Reversible modification of tissue-type plasminogen activator by methylphosphonate
      esters.
AB  - In spite of their rapid aqueous hydrolysis, 4-nitrophenyl 4-X-phenacyl
      methylphosphonates (X = H, (PMN) CH3, CH3O, Cl and NO2) inactivate many serine
      proteases of the pancreatic and blood coagulation systems efficiently. The rate
      constants, K/Ki, for the inactivation of tissue-type plasminogen activator enzyme
      (t-PA) are 470-750 M-1 S-1 with PMN, 4-CH3-PMN, and 4-CH3O-PMN in pH 7.8, 0.05 M
      Tris buffer at 7.0 +/- 0.5 degrees C, but t-PA cannot be inhibited with the 4-Cl
      and NO2 derivatives due to rapid competing hydrolysis. Enzyme activity returns
      from each enzyme-adduct at a characteristic rate, due to a self-catalyzed
      intramolecular reactivation process. The rate constants for spontaneous
      reactivation of t-PA from the adducts formed with the three inhibitors are K =
      0.25-12.3 x 10(-2) min-1 at pH 7.4 and 25.0 +/- 0.1 degrees C and pH-dependent
      with an apparent pK approximately 8.3. The recovery of t-PA activity from the
      adducts in 40% human plasma buffered at pH 7.4 is the same or twice that in plain
      buffer. The presence of fibrin has a slight effect on inactivation but not on
      reactivation. The modulation of enzyme activity by reversible generation of the
      phosphonylated adducts has potential for medical application.

PMID- 8735840
TI  - Ophiobolin M and analogues, noncompetitive inhibitors of ivermectin binding with
      nematocidal activity.
AB  - A series of ophiobolins were isolated from a fungal extract based on their
      nematocidal activity. These compounds are non-competitive inhibitors of
      ivermectin binding to membranes prepared from the free-living nematode,
      Caenorhabditis elegans, with an inhibition constant of 15 microM. The ophiobolins
      which were most potent in the biological assays, ophiobolin C and ophiobolin M,
      were also the most potent compounds when evaluated in a C. elegans motility
      assay. These data suggest that the nematocidal activity of the ophiobolins is
      mediated via an interaction with the ivermectin binding site. The isolation,
      structure and biological activity of ophiobolins have been described.

PMID- 8735841
TI  - Longifolicin, longicoricin, and gigantetroneninone, three novel bioactive mono
      tetrahydrofuran annonaceous acetogenins from Asimina longifolia (Annonaceae).
AB  - Longifolicin (1), longicoricin (2) and (2,4-cis and trans)-gigantetroneninone
      (3), three novel bioactive mono-tetra-hydrofuran (THF) gamma-lactone acetogenins,
      were isolated from the leaves and twigs of Asimina longifolia (Annonaceae) by
      directing the fractionation with the brine shrimp lethality test (BST). The
      structures were elucidated based on spectroscopic and chemical methods. Compounds
      1-3 showed selective and potent cytotoxicities to certain human tumor cell lines.

PMID- 8735842
TI  - Heterocondensed quinazolones: synthesis and protein-tyrosine kinase inhibitory
      activity of 3,4-dihydro-1H,6H-[1,4] oxazino-[3,4-b]quinazolin-6-one derivatives.
AB  - 1-Benzylidene (2-14) and 1-phenylhydrazono derivatives (15-29) of 3,4-dihydro
      1H,6H-[1,4]oxazino[3,4-b]quinazolin-6-one (1) were obtained from the condensation
      reactions of 1 with a series of aromatic aldehydes and by direct diazonium
      coupling with aryl-diazonium chlorides. The substances were tested for their
      ability to inhibit the tyrosine kinase activity of SW-620 (human colon carcinoma)
      cells. Compounds 8, 10, 12 and 13 showed remarkable inhibitory activity.

PMID- 8735843
TI  - Synthesis of 2'-deoxyuridine 5'-(alpha,beta-imido) triphosphate: a substrate
      analogue and potent inhibitor of dUTPase.
AB  - The dUDP analogue, 2'-deoxyuridine 5'-(alpha,beta-imido)diphosphate (dUPNP) was
      synthesized. The corresponding triphosphate analogue (dUPNPP) was prepared by
      enzymic phosphorylation of dUPNP using the enzyme pyruvate kinase and
      phosphoenolpyruvate as the phosphate donor. This method was successful in
      phosphorylating the imidodiphosphate analogue of 2'-deoxythymidine (dTPNP) to 2'
      deoxythymidine 5'-(alpha, beta-imido)triphosphate (dTPNPP), in contradiction to a
      previous report. The properties of dUPNPP have been tested using the enzyme
      dUTPase from Escherichia coli. This enzyme, having a crucial role in nucleotide
      metabolism, is strictly specific for its substrate (dUTP) and catalyzes the
      hydrolysis of the alpha, beta-bridge, resulting in dUMP and pyrophosphate.
      Replacement of the alpha, beta-bridging oxygen in dUTP with an imido group
      resulted in a nonhydrolyzable substrate analogue and a potent competitive
      inhibitor of dUTPase (Ki = 5 microM). The analogue prepared (dUPNPP) may be
      utilized in crystallographic studies of the active site of dUTPase to provide
      knowledge about specific interactions involved in substrate binding and as a
      parental compound in design of dUTPase inhibition for medical purposes.

PMID- 8735844
TI  - Inhibition of adhesion molecule expression by N-alkylthiopyridine
      benzo[b]thiophene-2-carboxamides.
AB  - The surface levels of ICAM-1 and E-selectin on activated endothelial cells can be
      reduced by 3-alkoxybenzo[b]thiophene-2-carboxamides. This property is shared by
      several N-alkylthiopyridine substituted imides. Combining structural elements of
      these two diverse series lead to a new class of small molecule inhibitors of
      adhesion molecule expression.

PMID- 8735845
TI  - Role of N- and C-terminal substituents on the CCK-B agonist-antagonist
      pharmacological profile of Boc-Trp-Phg-Asp-Nal-NH2 derivatives.
AB  - Among the CCK derivatives, the tetrapeptide Boc-Trp-Phg-Asp-Nal-NH2 (1) behaves
      as a short potent CCK-B agonist which led to the development of an efficient
      peptidase-resistant CCK-B antagonist by bismethylation of its terminal CONH2
      group. Further modifications of the N- and C-terminal moieties of 1 have been
      performed and are described in this paper, together with the pharmacological
      profile of the novel synthetized compounds. Introduction of more bulky
      substituents than NalNH2 on the C-terminal part decreased the CCK-B receptor
      binding affinity. In the series of N-protected tetrapeptides X30-Phg31-Asp32
      Nal33-N(CH3)2, the Boc-substituent was shown to be optimal among the N-protecting
      groups Boc, 2Adoc, propionyl or acetyl when X = Trp. On the other hand, when X =
      alpha MeTrp, its optimal N-protecting group was 2Adoc and its configuration was
      preferentially D. In the newly synthesized compounds, 13: 2Adoc-D-alpha MeTrp-Phg
      Asp-NalN(CH3)2 and 16: 2Adoc-D-alpha MeTrp-Phg-Asp-NalNH2 had the best CCK-B
      receptor affinities (KI = 3.5 and 3.4 nM, respectively) and were selected for
      further biological evaluation. Interestingly, when tested for their capacity to
      influence inositol phosphate formation, induced by CCK8 in CHO cells transfected
      with the rat CCK-B receptor, compound 13 behaved as a full CCK-B antagonist with
      an IC50 value of 18 +/- 1 nM, being as potent as the antagonist L-365,260 and PD
      134,308 (IC50 values respectively, 39 +/- 17 and 30 +/- 2 nM), whereas compound
      16 was found to behave as a partial CCK-B agonist. Indeed 16 behaved as an
      antagonist on the firing rate of rat CA1 hippocampal neurons and acted as an
      agonist in the pentagastrin stimulated gastric acid secretion (EC50 = 12 nmol/kg)
      in anesthetized rats. Compound 13 in contrast, was found to inhibit the
      pentagastrin action at a dose (ID50 = 0.56 mumol/kg) similar to the potent
      antagonist PD-134,308 (ID50 = 0.4 mumol/kg). The antagonist/agonist properties of
      compounds 13 and 16 show that both N- and C-terminal substituents modulate the
      pharmacological properties in the Boc-CCK4 derivatives presented here.

PMID- 8735846
TI  - Azulene derivatives as TXA2/PGH2 receptor antagonists--II. Synthesis and
      biological activity of 6-mono- and 6-dihydroxylated-isopropylazulenes.
AB  - In order to examine the correlation between activity and hydrophilicity of the
      side chain of sodium 3-[4-(4-chlorobenzenesulfonylamino)butyl]-6-isopropylazulene
      -1-sulfonate (KT2-962), a non-prostanoid TXA2/PGH2 receptor antagonist, one or
      two hydroxyl groups were introduced into the isopropyl moiety. A series of 6
      hydroxylated-isopropylazulenes were synthesized by regioselective oxidation of 6
      isopropylazulenes and their in vitro and in vivo antagonistic activities were
      studied. Both the primary and tertiary alcohols, monohydroxylated derivatives,
      exhibited potent biological activities comparable to unmodified 6
      isopropylazulenes both in vitro and in vivo. In contrast, the activities of 1,2-
      and 1,3-diols of 6-substituted derivatives, markedly decreased, but recovered by
      O-isopropylidenation of the dihydroxyl moiety. These findings indicate that the
      moderate hydrophobicity of substituent at the 6-position of the azulene ring
      might be required for the activity and the size of the substituent at this
      position, not so rigid for keeping potent biological activity.

PMID- 8735847
TI  - Pyrrolo[2,3-d]pyrimidines and pyrido[2,3-d]pyrimidines as conformationally
      restricted analogues of the antibacterial agent trimethoprim.
AB  - Conformationally restricted analogues of the antibacterial agent trimethoprim
      (TMP) were designed to mimic the conformation of drug observed in its complex
      with bacterial dihydrofolate reductase (DHFR). This conformation of TMP was
      achieved by linking the 4-amino function to the methylene group by one- and two
      carbon bridges. A pyrrolo[2,3-d]pyrimidine, a dihydro analogue, and a
      tetrahydropyrido[2,3-d]pyrimidine were synthesized and tested as inhibitors of
      DHFR. One analogue showed activity equivalent to that of TMP against DHFR from
      three species of bacteria. An X-ray crystal structure of this inhibitor bound to
      Escherichia coli DHFR was determined to evaluate the structural consequences of
      the conformational restriction.

PMID- 8735848
TI  - 5'-linked lipid-oligodeoxyridonucleotide derivatives as inhibitors of human
      immunodeficiency virus replication.
AB  - The covalent attachment of a phospholipid moiety, bound to the 5'-ends of
      phosphodiester and phosphorothioate oligonucleotides (L-ODNs and LS-ODNs), was
      achieved using H-phosphonate chemistry, and the lipid-oligonucleotides were
      assayed for the inhibition of virus replication in HIV-1 infected MT-4 cells. In
      the anti-HIV activity test, lipid-phosphorothioate oligonucleotides showed higher
      anti-HIV activities than non-lipid-phosphorothioate oligonucleotides, at the low
      concentration of 0.04 microM. LS-ODNs can inhibit HIV-1 reverse transcriptase
      activity through interactions with the enzyme. We found that the covalent
      attachment of a phospholipid group to the 5'-end of the phosphorothioate
      oligonucleotide enhances its nonsequence specific anti-HIV activity.

PMID- 8735849
TI  - Studies on the synthesis and biological activities of 4'-(R)-hydroxy-5'-(S)
      hydroxymethyl-tetrahydrofuranyl purines and pyrimidines.
AB  - A series of 4'-(R)-hydroxy-5'-(S)-hydroxymethyl-tetrahydrofuranyl purines and
      pyrimidines were synthesized by the reaction of 3,4-epoxy-5-(S,trans)
      dimethoxymethyl-tetrahydrofuran and nucleobases under the catalysis of potassium
      tert-butoxide and 18-crown-6. Compounds 6a, 6c and 7b have shown significant
      inhibition on the growth of HL-60 cells. The phosphotriester and phosphodiester
      of isonucleoside 8a-d were synthesized and cytotoxic activities were reported.
      The conformation of isonucleosides in solution was studied by 1H NMR.

PMID- 8735850
TI  - Enhancing effects of alpha-,beta-monoglycosylceramides on natural killer cell
      activity.
AB  - We examined the in vitro and in vivo natural killer (NK) cell activity enhancing
      effects of alpha-, beta-galactosylceramide (GalCer) and alpha-, beta
      glucosylceramide (GluCer) which have the same ceramide moiety, and of other alpha
      , beta-GalCer having a different ceramide portion, and found that alpha-types
      show stronger enhancing effects than beta-types and the alpha-GalCer possesses
      the most potent activity among GalCers and GluCers having the same ceramide
      moiety. When the comparison of tumor growth inhibitory effects of alpha, beta
      GalCer on mice subcutaneously inoculated with B16 cells was performed, the alpha
      GalCer showed stronger suppressive activity than its beta-type, paralleling their
      enhancing effects on NK cell activity. These results suggest that the manner of
      combination between sugar and ceramide plays an important role in antitumor
      activity as well as enhancing effect on NK cell activity of GalCers.

PMID- 8735852
TI  - The rationale for use of topical corticosteroids in allergic rhinitis.
AB  - The rationale for using topical corticosteroids in the treatment of allergic
      rhinitis is that high drug concentrations can be achieved at receptor sites in
      the nasal mucosa, with minimal risk of systemic adverse effects. Topical
      corticosteroids have been demonstrated to reduce the number of Langerhans' cells
      (or their markers) in the nasal mucosa, and this is thought to attenuate antigen
      presentation. T lymphocytes have been identified as being significant in
      orchestrating the immune-inflammatory response, particularly the TH2 cells, which
      represent an important target for topical corticosteroids. TH2 cell-evoked mast
      cells and basophils are the sole producers of histamine, a mediator of major
      importance for rhinitis symptoms. Several studies have shown that the increased
      number of mast cells and basophils in the epithelium following antigen
      challenge/exposure, are markedly reduced by topical corticosteroids. Furthermore,
      the number of eosinophils, an important morphological marker of allergic
      rhinitis, can be profoundly reduced by treatment with topical corticosteroids.
      The rationale for topical treatment is strengthened by evidence of inhibition of
      cytokine release from surface epithelial cells, resulting in reduced recruitment
      and activation of mast cells, basophils, and eosinophils, which may be attributed
      to the high drug concentration achieved in epithelial cells. Ongoing inflammation
      in the mucous membrane is indicated by entry of plasma into the nasal lumen which
      subsides with the anti-inflammatory efficacy of topical corticosteroids. In
      contrast to antihistamine therapy, which has little effect on nasal blockage,
      pretreatment with topical corticosteroids results in almost complete attenuation
      of late-phase symptoms including nasal blockage, and moderate efficacy in early
      phase symptoms. Clearly, the spectrum of anti-inflammatory activity afforded by
      topical corticosteroid therapy is of clinical significance in reducing the three
      major symptoms of allergic rhinitis- sneezing, watery rhinorrhoea and nasal
      blockage.

PMID- 8735851
TI  - Structure-activity relationships of benzimidazoles and related heterocycles as
      topoisomerase I poisons.
AB  - A series of substituted 2-(4-methoxyphenyl)-1H-benzimidazoles were synthesized
      and evaluated as inhibitors of topoisomerase I. The presence of a 5-formyl-, 5
      (aminocarbonyl)-, or 5-nitro group (i.e., substituents capable of acting as
      hydrogen bond acceptors) correlated with the potential of select derivatives to
      inhibit topoisomerase I. In contrast to bi- and terbenzimidazoles, the
      substituted benzimidazoles that were active as topoisomerase I poisons exhibited
      minimum or no DNA binding affinity. 5-Nitro-2-(4-methoxyphenyl)-1H-benzimidazole
      exhibited the highest activity and was significantly more active than the 4-nitro
      positional isomer. The 5- and 6-nitro derivatives of 2-(4-methoxyphenyl)
      benzoxazole, 2-(4-methoxyphenyl)benzothiazole, and 2-(4-methoxyphenyl)indole were
      synthesized and their relative activity as topoisomerase I inhibitors determined.
      None of these heterocyclic analogues were effective in significantly inhibiting
      cleavable-complex formation in the presence of DNA and topoisomerase I,
      suggesting a high degree of structural specificity associated with the
      interaction of these substituted benzimidazoles with the enzyme or the enzyme-DNA
      complex. In evaluating their cytotoxicity, these new topoisomerase I poisons also
      exhibited no significant cross-resistance against cell lines that express
      camptothecin-resistant topoisomerase I.

PMID- 8735853
TI  - Antihistamines: topical vs oral administration.
AB  - The pathogenesis of allergic rhinitis is complex, involving not only histamine
      and mast cell-derived tryptase, but also eosinophil- and neutrophil-derived
      mediators, cytokines, and intercellular cell adhesion molecules (ICAM-1). It is
      surprising that antihistamines, which block only one component of the process,
      have proved so effective in the management of allergic rhinitis. Research has
      therefore focused on whether antihistamines have additional pharmacological
      activities. In vitro studies have shown that high concentrations of second
      generation antihistamines can block inflammatory mediator release from basophils
      and mast cells, and reduce ICAM-1 expression in epithelial cell lines. In vivo
      studies have also shown an effect on the allergen-induced inflammatory reaction;
      both oral and intranasal antihistamines cause a reduction in nasal symptoms and
      inflammatory cell influx. Oral terfenadine and cetirizine and intranasal
      levocabastine and azelastine have also demonstrated a lowering of ICAM-1
      expression on epithelial cells. With regard to clinical efficacy, topical
      levocabastine (0.5 mg/mL eye drop solution and 0.5 mg/mL nasal spray) was shown
      to be more effective than oral terfenadine (60 mg twice daily) in relieving
      ocular itch (P = 0.02) and reducing nasal symptoms in allergic
      rhinoconjunctivitis. In a further study, levocabastine eye drops were as
      effective and well tolerated as sodium cromoglycate in seasonal allergic
      rhinitis. Intranasal azelastine (0.28 mg twice daily) showed a trend for superior
      relief of rhinorrhoea and nasal obstruction compared with oral terfenadine (60 mg
      twice daily). In addition, intranasal azelastine (0.28 mg twice daily) resulted
      in significant reductions in sneezing, nasal obstruction, rhinorrhoea and itching
      in perennial rhinitis, compared with the lower efficacy of beclomethasone
      dipropionate (0.1 mg twice daily). As well as benefits in efficacy, topical
      administration is associated with improved safety. Some antihistamines,
      particularly those metabolized in the liver, are associated with occasional
      reports of severe side-effects. It is therefore logical to administer
      antihistamines directly to the target organ.

PMID- 8735855
TI  - Nasal polyps: medical or surgical management?
AB  - Nasal polyposis is considered to be a non-IgE-mediated inflammatory condition of
      the nose and sinuses, often associated with chronic non-allergic rhinitis,
      aspirin intolerance and non-allergic asthma. The aetiology of nasal polyposis is
      unknown. The main symptoms are nasal obstruction and disturbance of the sense of
      smell. Occlusion of the nasal passage by a few large polyps could be treated by
      simple polypectomy to help the patient breathe through the nose. Polypectomy per
      se does not worsen asthma. Other surgical procedures can be performed, depending
      on the degree of the disease. The aim of surgery is to restore the physiological
      properties of the nose by making the nose as free from polyps as possible, and to
      allow drainage of infected sinuses. Complementary medical treatment of polyposis
      is always necessary, as surgery cannot treat the inflammatory component of the
      mucosal disease. In this respect, topical corticosteroids have long been the
      drugs of choice to reduce the size of polyps, to prevent recurrence after
      surgery, and are often the main treatment for the disease in many patients.
      Fluticasone propionate has now been shown to be at least as effective as
      beclomethasone dipropionate as a medical tool in the management of polyposis.
      Short-term treatment with systemic corticosteroids is an alternative method of
      inducing remission and controlling nasal polyps. However, in most patients with
      nasal polyps, treatment consists of both medical and surgical management.

PMID- 8735854
TI  - Fluticasone propionate: topical or systemic effects?
AB  - Intranasal corticosteroids have been shown to be more effective than oral
      antihistamines for the treatment of seasonal allergic rhinitis. However, there
      are some who question whether intranasally administered corticosteroids should be
      used due to potential systemic effects. Fluticasone propionate, a potent
      corticosteroid with high specificity for the glucocorticoid receptor, is
      available as an aqueous nasal spray for the treatment of allergic rhinitis. To
      determine whether the efficacy of fluticasone propionate aqueous nasal spray
      (FPANS) was due to direct topical effects on the nasal mucosa or to indirect
      systemic effects following absorption from the nasal mucosa or from the swallowed
      portion of an intranasal dose, FPANS 200 micrograms once daily was compared with
      oral fluticasone propionate 5 mg or 10 mg once daily or placebo for 2 weeks in
      patients with seasonal allergic rhinitis. These oral dosages were chosen to yield
      low but consistent plasma fluticasone propionate concentrations. Both clinician-
      and patient-rated scores for nasal obstruction, rhinorrhoea, sneezing, and nasal
      itching were significantly lower in the intranasal fluticasone propionate group
      compared with both oral fluticasone propionate groups. A separate placebo
      controlled study was conducted in patients with perennial rhinitis to determine
      if administration of FPANS 200 micrograms once daily for 1 year was associated
      with adverse systemic effects. At the 1-year assessment, there were no
      significant effects on bone mineral density or on biochemical markers of bone
      turnover. Similarly, there was no evidence of posterior subcapsular cataracts nor
      of glaucoma. Furthermore, there were no significant effects on hypothalamic
      pituitary adrenal axis function as assessed by plasma cortisol and 24-h urinary
      cortisol response to the 6-h cosyntropin stimulation test. These data confirm
      that the efficacy of FPANS for the treatment of allergic rhinitis results from
      direct topical effects, thus reducing the likelihood of adverse systemic effects.

PMID- 8735856
TI  - Neuroregulation of the nose and bronchi.
AB  - The vascular beds, submucosal glands, and airway vasculature are the three
      primary effector tissues in the airways, and all are under the control of the
      parasympathetic (vagal) and sympathetic nervous systems. Parasympathetic nerves
      play a more important role in smooth muscle contraction and gland secretion. The
      complex neurogenic mechanisms initiated by activation of sensory nerves have been
      clarified to a large extent by studies on experimental animals. For example,
      inflammation or an allergic response will cause neurogenic inflammation due to
      axon reflexes; central nervous reflexes will modulate activity in all of the
      effector tissues; and these reflex responses will be modulated by local reflexes
      via parasympathetic ganglia. Similar mechanisms are suspected in humans, but
      their importance still needs to be fully established.

PMID- 8735857
TI  - Response of nose and bronchi to exercise in asthma and rhinitis: similarities and
      differences.
AB  - The response of asthmatic patients to exercise differs from that of healthy
      subjects, and the mechanisms responsible for the exercise-induced
      bronchoconstriction in the former group remain uncertain. The severity of
      bronchospasm may be related to water loss from the respiratory tree, but there
      are conflicting explanations for this. The response of the nose to exercise, in
      healthy subjects or in patients with asthma and rhinitis, has been the subject of
      few investigations, but a recent study found that the nose responds in a
      different fashion to the bronchi in patients with rhinitis and asthma. The
      bronchial tree responds by narrowing, while the nose becomes more patent. There
      is evidence that the bronchi are the main sites of airway narrowing in exercise
      induced bronchoconstriction, while there can also be simultaneous tracheal
      dilatation. In addition, it now appears that the nasal response to exercise in
      all subjects parallels that of the trachea. In total, the results suggest that
      different mechanisms are responsible for regulating the patency of the upper and
      lower airways.

PMID- 8735858
TI  - Challenge tests in nose and bronchi: pharmacological modulation of rhinitis and
      asthma.
AB  - In order to study the pathophysiology of allergic airway disease and its response
      to pharmacotherapy, allergic and non-allergic provocation challenge techniques
      can be employed. Lower airway challenge has been used widely, but the use of
      nasal challenge is becoming more widespread as its advantages are realized. New
      measurement techniques are also being used (e.g. acoustic rhinometry), along with
      more classical methods such as spirometry, peak airflow rate and symptom scores,
      to determine the response to challenge. In the lungs, allergen challenge produces
      a biphasic response, which is less clearly defined in the nose. Topical histamine
      challenge closely resembles the effects of an allergic reaction and acts by
      stimulating sensory nerve endings. Methacholine is also often used for nasal
      challenge (often in addition to histamine), due to its effects on glandular
      sensitivity. Exercise induces bronchoconstriction in asthmatics and can be
      imitated by inhalation of cold, dry air. Cold air induces glandular
      hypersecretion and nasal discharge in normal subjects, which is increased in
      severity in rhinitic patients. Drug effect investigations using antihistamines
      have shown that histamine is important in producing the symptom of sneezing,
      whereas nasal blockage is due to vasodilatation rather than plasma exudation and
      oedema. Beta 2-agonists reduce allergen-induced symptoms by stabilizing mast
      cells, whereas cholinoceptor antagonists reduce watery nasal secretion. Increased
      responsiveness of sensory nerves and nasal glands is a characteristic clinical
      feature of asthma and rhinitis, which is responsible for the symptomatology.
      These effects can be reduced by topical corticosteroids.

PMID- 8735859
TI  - Pathology of rhinitis and bronchial asthma.
AB  - Studies of the pathology of rhinitis and asthma have identified similarities and
      differences between these two clinical conditions. With regard to symptoms, both
      the nose and the lower airways respond to neural stimulation by irritant
      substances, but a major difference is that engorgement of the capacitance vessels
      is the main cause of nasal obstruction in rhinitis, while muscle constriction is
      the major determinant of lower airway narrowing. There are also similarities and
      differences with respect to the role of inflammatory cells. In both conditions
      there is evidence of allergen-induced mast cell activation, with production of an
      array of mediators (some mast cell-derived and others originating from a variety
      of other cell types). Eosinophilia is also characteristic of both diseases--it is
      prominent even in mild forms of asthma, but is low in pollen-sensitive rhinitics
      outside of the season. T-cell activation and production of cytokines plays an
      important role in the development and maintenance of allergic disease, but the
      level of T-cell activation may differ between asthma and rhinitis. Further
      research into differences in cellular activity and response to treatment between
      these two diseases may help define factors which will determine whether atopic
      disease is expressed in the upper, lower, or both parts of the respiratory tract.

PMID- 8735860
TI  - Dendritic cells in the lung: what is their relevance to asthma?

PMID- 8735861
TI  - Airway neuropeptides and neutral endopeptidase in asthma.

PMID- 8735862
TI  - Overview on denominated allergens.

PMID- 8735863
TI  - Increased numbers of dendritic cells in the bronchial mucosa of atopic asthmatic
      patients: downregulation by inhaled corticosteroids.
AB  - BACKGROUND: Dendritic cells (DC) are the most potent antigen-presenting cells
      (APC) and stimulators of T cells. Dendritic cells are also likely to be essential
      for the initiation of allergic immune responses in the lung. However, there are
      not many data on the presence of dendritic cells in the airways of patients with
      atopic asthma and on the effects of corticosteroid-treatment on such dendritic
      cells. OBJECTIVE: We investigated the distribution of dendritic cells in the
      bronchial epithelium and mucosa of 16 non-smoking atopic asthmatic patients and
      eight healthy control subjects using detailed immunohistochemistry (CD1a, HLA-DR,
      L25 as markers for dendritic cells). METHODS: Eleven asthmatics were treated for
      2.5 years with bronchodilators only and five with bronchodilators and inhaled
      beclomethasone dipropionate (BDP), 800 micrograms daily. The patients were
      randomly sampled from a double-blind multicentre study. RESULTS: There were
      higher numbers of CD1a+ DC (P = 0.003), L25+ DC (P = 0.002) and HLA-DR expression
      (P = 0.042) in the bronchial mucosa of asthmatic patients compared with healthy
      controls. After 2.5 years of treatment, we found a significant increase in flow
      expiratory volume in 1 second (FEV1) (P = 0.009) and a significant decrease in
      hyperresponsiveness (PC20 histamine) (P = 0.013) in the corticosteroid group (n =
      5) compared with the bronchodilator group (n = 11). This clinical improvement in
      the corticosteroid-treated group was accompanied by significantly lower numbers
      of CD1a+ DC (P = 0.008), and HLA-DR expression (P = 0.028) in the bronchial
      mucosa than in the bronchodilator-treated group. CONCLUSION: Our data suggest
      that dendritic cells are involved in asthmatic inflammation and that
      corticosteroids may downregulate the number of dendritic.

PMID- 8735865
TI  - Analysis of the allergenic composition of rat dust.
AB  - BACKGROUND: Allergy to rats is an important occupational health problem. The
      allergens of rat urine have been well defined but those in rat room dust, a
      potentially important source of inhalant exposure, have not. OBJECTIVE: To
      describe the allergens present in rat room dust and to identify a suitable marker
      protein which may be used to quantify airborne rat allergen. METHODS: Dust
      collected from the air-conditioning system (bulk dust, 'bd') and with an air
      sampler (airborne dust, 'ad') were analysed by radioallergosorbent test (RAST)
      inhibition, immunoblotting and immunoblot inhibition techniques and comparisons
      made with hair and urine extracts prepared from adult male Wistar rats. RESULTS:
      Extensive crossreactivity was found between the extracts by RAST inhibition under
      different experimental conditions. Dust was more potent as an inhibitor than
      other extracts. The immunoblotting patterns of both dusts were similar although
      'ad' contained an allergen at 29 kDa not found in 'bd'. Forty-two sera from rat
      allergic subjects were used to identify 18 allergens in 'bd'. Three 'major'
      allergens were found; 100% of subjects had immunoglobulin (Ig)E to a 44 kDa
      allergen and 74% and 88% of subjects had IgE with bound to the 20.5 and 17 kDa
      allergens respectively. Immunoblot inhibition experiments identified the 17 kDa
      dust allergen as alpha 2u-globulin (Rat nI). CONCLUSIONS: Rat dust is a complex
      allergenic source. The 17 kDa dust allergen has immunological identity with Rat
      nI and is a suitable marker protein for the quantitation of airborne rat
      allergen.

PMID- 8735864
TI  - The effect of inhaled thiorphan on allergen-induced airway responses in asthmatic
      subjects.
AB  - BACKGROUND: Neuropeptides are likely to be implicated in the pathophysiology of
      allergen-induced airway responses. However, upon release in the airways,
      neuropeptides are potentially inactivated by neutral endopeptidase (NEP).
      OBJECTIVE: We hypothesized that NEP-inhibition by inhaled thiorphan (TH) would
      increase allergen-induced early (EAR) and late (LAR) asthmatic responses, and
      allergen-induced airway hyperresponsiveness to histamine in asthmatic subjects in
      vivo. The dose and dosing intervals of TH were derived from previous
      pharmacokinetic and dose-finding studies. METHODS: Nine non-smoking, atopic,
      asthmatic men with dual asthmatic responses to inhaled house-dust mite extract
      participated in a double-blind, placebo-controlled, cross-over study. During each
      study period PC20 histamine was measured 24 h before, and 3 and 24 h post
      allergen. TH (1.25 mg/mL, 0.5 mL) or placebo (P) were aerosolized pre-allergen,
      and three times at 2 h intervals post-allergen (total dose of TH: 2.5 mg). Forced
      expiratory volume in one second (FEV1) was recorded and expressed as percentage
      fall from baseline. The EAR (0-3 h) and the LAR (3-8 h) were defined as maximum
      percentage fall from the pre-allergen baseline and as corresponding areas under
      the time-response curves (AUC). RESULTS: As compared with P, TH failed to induce
      an acute effect on FEV1 at any of the timepoints (P > 0.08). There was no
      significant difference between P and TH in the EAR and the LAR: neither in terms
      of maximum percentage fall from baseline (mean +/- SEM: EAR: 22.3 +/- 4.7% (P)
      and 20.4 +/- 4.1% (TH), P = 0.75; LAR: 25.2 +/- 4.7% (P) and 26.4 +/- 5.8% (TH),
      P = 0.77) nor in terms of AUC (P = 0.76). Correspondingly, the changes in PC20
      histamine were not different between the two treatments (P > 0.40). CONCLUSION:
      We conclude that four adequate doses of the inhaled NEP-inhibitor, thiorphan,
      failed to potentiate allergen-induced airway responses in asthma. These results
      suggest that either neuropeptides do not play a predominant role in allergen
      induced airway responses, or that allergen challenge induces NEP-dysfunction in
      humans in vivo.

PMID- 8735866
TI  - Airborne dust antigen exposure and specific IgG response in the potato processing
      industry.
AB  - BACKGROUND: High prevalences of work-related respiratory symptoms in relation to
      organic dust exposure have been reported in the potato processing industry, but
      the responsible effect mechanisms are not known. OBJECTIVE: To study the possible
      role of a type III allergy in aetiology. METHODS: Specific immunoglobulin G (IgG)
      and IgG4 subclass antibodies against occupational airborne antigens were
      determined in sera from 131 potato processing workers and 36 non-exposed
      controls. Personal exposure to airborne antigens was measured, and a preliminary
      biochemical characterization was carried out. RESULTS: Specific IgG was
      detectable in almost all sera, but levels were significantly (P < 0.01) higher in
      potato processing workers compared with controls. Specific IgG4 was detectable in
      half of the workers' sera, but in none of the control sera. The antigens involved
      appeared to be heat-labile potato proteins. Antibody levels increased during the
      processing campaign in most workers, and this increase was dependent on the level
      of antigen exposure. Both the difference in IgG titres between the occupationally
      exposed group and the non-exposed group, and the exposure-related increase in
      specific IgG titres seemed to be mainly due to specific antibodies of the IgG4
      subclass. Specific antibodies showed a non-significant tendency to lower levels
      in workers with work-related respiratory symptoms. CONCLUSION: Occupational
      respiratory exposure in the potato processing industry leads to a strong humoral
      immune response, most pronounced for IgG4 subclass antibodies. Type III allergy
      is, however, unlikely to play a predominant role in the aetiology of respiratory
      effects.

PMID- 8735867
TI  - Induction of hyperresponsiveness in human airway tissue by neutrophils--mechanism
      of action.
AB  - BACKGROUND: The two main features of asthma are bronchial hyperresponsiveness and
      inflammation. The inflammatory response in asthma consists of infiltration and
      activation of a variety of inflammatory cells including neutrophils. Our previous
      studies have shown that stimulated neutrophil supernatants cause
      hyperresponsiveness of human bronchial tissue in vitro. OBJECTIVE: To investigate
      the effect of the sensitization status of the tissue and the albumin
      concentration used to prepare supernatants on the response of human bronchial
      tissue to stimulated neutrophil supernatants. METHODS: Neutrophil supernatants
      were prepared from human isolated blood in the presence of varying concentrations
      of albumin (0%, 0.1% and 4%). Neutrophil supernatants were added to sensitized
      and non-sensitized human isolated bronchial tissue which was stimulated with
      electrical field stimulation (EFS) (20 s every 4 min). Receptor antagonists
      specific for the prostaglandin and thromboxane (10(-7) M GR32191), platelet
      activating factor (10(-6) M WEB 2086), leukotriene D4 (10(-6) M MK-679) and
      neurokinin A (10(-7) M SR48968) receptors were used to identify neutrophil
      products responsible for the effects observed in the bronchial tissue. RESULTS:
      In non-sensitized human bronchial tissue, stimulated neutrophil supernatants
      induced a direct contraction in the presence of 0% and 0.1% but not 4% albumin.
      This contraction was due to leukotriene D4 as MK-679 completely inhibited the
      contraction. In contrast, stimulated neutrophil supernatants increased
      responsiveness of sensitized human bronchial tissue to EFS. The increased
      responsiveness was observed only in the presence of 0.1% albumin, with the site
      of modulation likely to be prejunctional on the parasympathetic nerve. The
      increased responsiveness was not inhibited by any of the antagonists tested.
      CONCLUSION: Sensitization status of the tissue and albumin concentration effect
      the responsiveness of human bronchial tissue to stimulated neutrophil
      supernatant. Our results suggest a possible role for neutrophils in
      hyperresponsiveness.

PMID- 8735868
TI  - Detection of transforming growth factor-beta in sputum from patients with
      bronchial asthma by eosinophil survival assay and enzyme-linked immunosorbent
      assay.
AB  - BACKGROUND: We have shown that interleukin-5 (IL-5) and granulocyte-macrophage
      colony-stimulating factor (GM-CSF) are present in sputum from patients
      experiencing acute asthma attacks, by eosinophil survival assay. The viability of
      guinea-pig eosinophils was significantly increased in the presence of such sputum
      extracts after 3 days' culture, and it was inhibited by the addition of anti-IL-5
      and anti-GM-CSF antibodies. However, the contribution of IL-5 to the increase in
      eosinophil viability was less than expected from the values of IL-5 measured by
      enzyme-linked immunosorbent assay (ELISA). Therefore, we speculated that
      something in sputum inhibited the function of IL-5. OBJECTIVE: Transforming
      growth factor-beta (TGF-beta) was the only cytokine we tested that inhibited the
      prolongation of survival of guinea-pig eosinophils induced by IL-5. The objective
      of this study is to detect TGF-beta in the same sputum. METHODS: Guinea-pig
      eosinophils were cultured with or without anti-TGF-beta antibody in the presence
      of sputum extracts, and the eosinophil viability was counted after 3 days.
      Measurement of TGF-beta 1 in sputum was performed by ELISA. RESULTS: Eosinophil
      viabilities with and without anti-TGF-beta antibody were 79.7 +/- 2.9% and 69.0
      +/- 2.7%, respectively, and the difference between them was statistically
      significant (P < 0.05, n = 9). The concentration of TGF-beta 1 in the sputum was
      21.7 +/- 3.3 ng/mL (n = 9). CONCLUSION: These observations suggest that TGF-beta
      is present in sputum from patients with bronchial asthma.

PMID- 8735869
TI  - In vitro primary sensitization of hapten-specific T cells by cultured human
      epidermal Langerhans cells--a screening predictive assay for contact sensitizers.
AB  - BACKGROUND: The need to develop predictive tests which could identify potential
      allergens has been recognized for many years. There is as yet no accepted in
      vitro method for the assessment of contact sensitizers. OBJECTIVE: We have tested
      the ability of a range of contact allergens to induce in vitro primary
      sensitization of autologous T cells. METHOD: T-cell proliferation induced by
      haptens using 2-day cultured human Langerhans cells as antigen-presenting cell
      was assessed by 3H thymidine incorporation. Antigen specific stimulation was
      calculated as stimulation indexes. RESULTS: Strong allergens induced in vitro a
      primary T-cell response in all (trinitrophenyl, TNP: 13/13) or in the majority
      (fluorescein isothiocyanate, FITC: 7/10) of experiments. An irritant, sodium
      dodecyl sulfate (SDS), failed to generate a significant T-cell proliferation in
      any of the experiments (0/10). We obtained a significant lymphoproliferative
      response to weak sensitizers only in a limited number of experiments: (coumarin:
      1/12, citronellal: 0/10, hydroxycitronellal: 2/8). p-Phenylenediamine (PPDA), a
      prohapten and highly sensitizing chemical in vivo, generated primary
      sensitization in vitro in only one of six experiments, while Bandrowski's base
      (BB), a metabolization product of PPDA induced a significant T-cell response in
      all six experiments. CONCLUSION: The present in vitro model allows discrimination
      between two groups of substances: strong contact sensitizers (TNP, FITC, BB) on
      the one hand and weak sensitizers (coumarin, citronellal and hydroxycitronellal)
      and irritants (SDS) on the other hand. It could be used as a screening in vitro
      assay to eliminate strong contact allergens before further predictive animal
      tests have to be performed.

PMID- 8735870
TI  - Sequence polymorphisms of the Der p 3 house dust mite allergen.
AB  - BACKGROUND: The trypsin-like protein Der p 3 is a major allergen of
      Dermatophagoides pteronyssinus. Like other vertebrate and invertebrate trypsin
      like molecules, isoelectric-focusing studies with the natural Der p 3 protein
      have indicated that several isoforms exist. OBJECTIVE: To determine the extent of
      the sequence variation of the Der p 3 allergen and distinguish at the molecular
      level, whether the sequence isoforms represent allelic variants or multiple genes
      of the allergen. METHODS: Five cDNA clones of Der p 3 have been isolated from a
      lambda gt10 D. pteronyssinus library, using a radiolabelled polymerase chain
      reaction (PCR) Der p 3 P3WS1 probe and sequenced. Southern blot and inverse PCR
      analysis of Eco R1 digested genomic DNA was performed. RESULTS: Southern blot
      analysis of Eco R1 digested genomic DNA showed that the DNA encoding Der p 3 was
      located on a single 3.5 kb fragment and inverse polymerase chain reaction
      analysis (PCR) of this DNA showed that there was only a single Der p 3 gene on
      this 3.5 kb fragment. The nucleotide sequence of one of the clones was identical
      to the original Der p 3 P3WS1 clone and two clones differed only in their 3'
      untranslated sequences. The other two contained nucleotide changes which lead to
      several substitutions at the amino acid level, both conservative and non
      conservative. Clone 3 had 98.7% identity with Der p 3 P3WS1. One clone for which
      the full sequence was not available (clone 4) had only 84.4% identity with the
      original clone and is therefore consistent with an isoallergen. CONCLUSIONS:
      These data along with our previous genomic sequence shows that for the most part,
      the Der p 3 allergen has only minor sequence variations (variants) although the
      isoallergen indicated by clone 4 needs further investigation. It is now evident
      that Der p 3 is encoded by a single gene and that most cDNA clones constructed
      from commercial mites show only minor sequence variation similar to that observed
      for the group 1 and group 2 house dust mite allergens.

PMID- 8735871
TI  - Allergy and the risk of sudden infant death syndrome. The Members of the New
      Zealand Cot Death Study Group.
AB  - BACKGROUND AND OBJECTIVE: There are several sources that suggest that there is a
      link between allergy and sudden infant death syndrome. We endevavoured to look
      for evidence of an association between allergic disease and the risk of sudden
      infant death syndrome (SIDS). METHODS: A nationwide case-control study covering a
      region with 78% of all births in New Zealand during 1987-90. Interviews were
      completed with the parents of 393 (81.0% of total) infants who died from the
      sudden infant death syndrome (SIDS), and 1592 (88.4% of total) control families
      who were a representative sample of all hospital births in the study region.
      RESULTS: Eczema was reported in 13.9% control infants compared with only 8.0% of
      the SIDS infants, univariate odds ratio for this in terms of risk for SIDS was
      0.56 (95% confidence interval 0.37, 0.84) for infants with eczema compared with
      those without. This lesser risk for SIDS was unchanged when adjusted for
      potential confounding factors. The risk of SIDS was not associated with reported
      cow's milk reactions or a family history of allergic symptoms once adjustments
      were made for possible confounding factors. CONCLUSION: Infants with skin
      disorders identified by their parents as eczema had a low risk for SIDS. Families
      can be reassured that atopy is not a risk factor for SIDS.

PMID- 8735872
TI  - Major Dermatophagoides mite allergen, Der 1, in soft toys.
AB  - BACKGROUND: Allergen avoidance is recommended when treating atopic asthma.
      OBJECTIVES: Soft toys are often kept in close proximity to children and may serve
      as a source of exposure. Due to the potential danger from the mite allergen
      content of these toys, Der 1 from toys was measured. METHODS: We quantified the
      level of Der 1 (Der p 1 + Der f 1) in both 30 new and 174 old soft toys (weight
      216 +/- 2.5 g, height 26.5 +/- 3.4 cm), as well as in washed and in vacuumed soft
      toys. Dust was collected using an electric vacuum cleaner. Der 1 was measured by
      monoclonal antibody-based enzyme-linked immunosorbent assay (MoAb-ELISA).
      RESULTS: In brand new toys Der 1 was 0.1 microgram/g of dust, and in toys used
      for 1 year, 9.0; 2 year, 22.2; 3 year, 18.9; and more than 4 year, 22.7
      micrograms/g of dust. Der 1 in new toys was measured every 4 months for 1 year.
      Der 1 rapidly increased 10- to 20-fold in the first 4 months, but there was no
      clear seasonal change. In toys washed using a chemical detergent or cleaned using
      a vacuum cleaner, there was a stastistically significant (P < 0.001) decrease in
      Der 1 in the washed group, but not in the vacuumed group. CONCLUSION: These
      results confirm that mite allergens accumulate rapidly in toys to form a
      potentially important source of allergens and that washing toys with a chemical
      detergent is effective in the reduction of allergens.

PMID- 8735873
TI  - Evidence of antibodies to erythromycin in serum of a patient following an episode
      of acute drug-induced hepatitis.
AB  - BACKGROUND: A patient who had taken erythromycin orally developed mild signs of
      hepatocellular damage and appeared to became sensitized. After a fortuitous oral
      intake of the antibiotic, 18 months later, the patient developed an extensive
      intrahepatic cholestasis. OBJECTIVE: To confirm the allergic nature of this form
      of hepatitis by demonstrating the presence of serum antibodies directed at the
      drug. METHODS: Primary cultured human hepatocytes were used to investigate
      whether erythromycin can covalently bind to hepatocytes; and to demonstrate the
      presence of drug-directed immunoglobulins in the serum of the patient. RESULTS:
      As a consequence of its metabolism by hepatocytes, a small percentage of
      erythomycin remained bound to hepatocyte proteins. The extent of covalent binding
      varied among hepatocytes from different donors, and was not observed in
      metabolically inactive hepatocytes. Antibodies able to bind erythromycin were
      detected in the serum of the patient. When this serum was added to a human
      hepatocyte culture that had been previously incubated with the drug, binding of
      immunoglobulins was observed around the cell membrane and close to pseudo-bile
      canaliculi, thus indicating the presence of antibodies able to recognize
      erythromycin-labelled hepatocytes. CONCLUSIONS: The existence of serum antibodies
      directed at erythromycin haptens in this patient strongly suggests an allergic
      mechanism for this drug-induced hepatitis.

PMID- 8735874
TI  - Characteristics of histamine release from cultured human mast cells.
AB  - BACKGROUND: The mast cell is one of the important cells in the pathogenesis of
      allergic disorders. However, isolating human mast cells is a laborious procedure.
      Recently, cultured human mast cells raised from umbilical cord blood cells have
      become available. It is necessary to examine whether these cells are useful in
      investigating the role of mast cells in human diseases. OBJECTIVE: The phenotype
      of mast cells depends on their anatomical sites. To examine which phenotype of
      mast cells these cultured mast cells most closely resemble, their ability to
      release was investigated. METHODS: The mast cells were raised from human
      umbilical cord blood cells in the presence of stem cell factor and interleukin-6.
      To determine the mast cell subtypes, the mast cells were immunocytochemically
      stained for tryptase and chymase. The cultured mast cells were then stimulated
      with various secretagogues, and histamine release was measured by a fluorometric
      technique using high-performance liquid chromatography. RESULTS: The
      immunocytochemical staining for mast cell proteases revealed that virtually all
      cells contained tryptase, the definitive marker of mast cells, and that about a
      quarter of the cells contained chymase. Anti-IgE effectively stimulated these
      mast cells to release histamine in a dose-dependent, time-dependent manner. The
      release was completed in about 30 min. One of the non-specific stimuli, calcium
      ionophore A23187, also induced histamine release in a dose-dependent, time
      dependent manner. In contrast, compound 48/80 and substance P failed to induce
      histamine release from these cells. CONCLUSION: Cultured human mast cells
      resemble lung mast cells in their ability to release histamine. They will help in
      studying the functional properties of human mast cells and may contribute to
      clarifying the pathophysiology of human allergic diseases.

PMID- 8735875
TI  - Parainfluenza-3-virus infection enhances allergic sensitization in the guinea
      pig.
AB  - BACKGROUND: Viral respiratory tract infections have been previously considered to
      be associated with induction of allergic sensitization. OBJECTIVE AND METHODS: In
      order to investigate this relationship in an animal model, guinea-pigs were
      inoculated intranasally with Parainfluenza-3-(PI-3) virus (n = 16) or virus-free
      culture medium (controls, n = 12), sensitized at day 4 with inhaled ovalbumin
      (OA) and challenged 3 weeks later with inhaled OA using specific bronchial
      provocation testing with body plethysmographic measurement of compressed air
      (CA). Furthermore, specific anti-OA-IgG1-antibodies in serum before challenge
      were determined by enzyme linked immunosorbent assay (ELISA). For investigation
      of airway epithelium permeability horseradish peroxidase (HRP) was inhaled at day
      4 after inoculation by six animals, and HRP serum concentrations were determined
      by a direct ELISA 30 min after inhalation. RESULTS: PI-3 infected animals were
      found to be significantly more sensitized to OA compared with controls, with
      higher CA values (P < 0.001) on specific bronchial provocation and with increased
      specific anti-OA-IgG1 titers. Serum-HRP concentrations were about 20 times higher
      in the infected animals compared with controls. PI-3 infected and sham-infected
      animals had comparable bronchial reactions on specific provocation with OA when
      sensitized systemically. CONCLUSIONS: We conclude that viral respiratory tract
      infection with PI-3 virus enhances inhalative allergic sensitization in the
      guinea-pig. Increased mucosal permeability to antigens may be an important
      pathophysiological mechanism.

PMID- 8735876
TI  - Adenosine A2 receptor-mediated excitatory actions on the nervous system.
AB  - The distribution, molecular structure and role of adenosine A2 receptors in the
      nervous system, is reviewed. The adenosine A2a receptor subtype, identified in
      the nervous system with ligand binding, functional studies or genetic molecular
      techniques, has been demonstrated in the striatum and other basal ganglia
      structures, in the hippocampus, in the cerebral cortex, in the nucleus tractus
      solitarius, in motor nerve terminals, in noradrenergic terminals in the vas
      deferens, in myenteric neurones of the ileum, in the retina and in the carotid
      body. The A2b receptors have been identified in glial and neuronal cells, and may
      have a widespread distribution in the brain. Activation of adenosine A2a
      receptors can enhance the release of several neurotransmitters, such as
      acetylcholine, glutamate, and noradrenaline. The release of GABA might be either
      enhanced or inhibited by A2a receptor activation. The A2 receptor activation also
      modulates neuronal excitability, synaptic plasticity, as well as locomotor
      activity and behaviour. The ability of A2 receptors to interact with other
      receptors for neurotransmitters/neuromodulators, such as dopamine D2 and D1
      receptors, adenosine A1 receptors, CGRP receptors, metabotropic glutamate
      receptors and nicotinic autofacilitatory receptors, expands the range of
      possibilities used by adenosine to interfere with neuronal function and
      communication. These A2 receptor-mediated adenosine actions might have potential
      therapeutic interest, in particular in movement disorders such as Parkinson's
      disease and Huntington's chorea, as well as in schizophrenia, Alzheimer's
      disease, myasthenia gravis and myasthenic syndromes.

PMID- 8735877
TI  - Neuronal plasticity induced by neonatal monocular (and binocular) enucleation.
AB  - Monocular (ME) and binocular enucleation has become a useful experimental tool
      for analyzing the mechanisms of neural plasticity. ME when performed during an
      early postnatal period (up to 15 days after birth) initiates a series of adaptive
      reactions in the visual (and other sensory) system(s) which tend to compensate
      for the lost sensory capacity. Extirpation of one eye (usually the right)
      destroys afferents to both lateral geniculate bodies dorsal nucleus (CGLd) and
      superior colliculi (CS), being severely impaired by the degeneration of retino
      geniculate and collicular synapses. The sprouting of retinogeniculate fibers
      coming from the remaining eye replaces these synapses in both CGLds. Ipsilateral
      representation of the remaining eye (usually of minor significance) becomes
      extended in the left CGLd and consequently in the left visual area, just as in
      the superior colliculi. A similar but somewhat smaller extension takes place in
      the contralateral CGLd and visual cortex. The strengthening of commissural
      connections results in a remarkable extension of callosally connected stripes and
      patches in both hemispheres. After ME in the critical period, the control over
      behavior is taken over by the remaining eye. Its power of resolution is improved
      because of the higher survival of (mainly ipsilaterally projecting) ganglion
      cells. Therefore, both hemispheres are still available for storing visual
      information. In ME rats the learning of visual tasks requires both hemispheres,
      but relearning is still possible after extirpation of the contralateral one. The
      possible two main mechanisms of adaptive plastic changes are: (i) replacement of
      degenerated synapses by sprouting collaterals of ingrowing foreign fibers, and
      (ii) neurons having morphologically intact but inactive synapses establishing
      connections with afferent fibers other than the usual. The same mechanism is seen
      operating in cross-modal adaptive reactions as well.

PMID- 8735878
TI  - Responses of basal forebrain cholinergic neurons to damage in the adult brain.
AB  - The basal forebrain cholinergic system, which projects to all cortical areas, is
      a good model for the study of the responses of central nervous system (CNS)
      neurons to injury. Much is known about the specific neurotrophic factors of basal
      forebrain cholinergic neurons, and there are many techniques available to chart
      the progress of degeneration and recovery of cholinergic neurons after damage.
      There is also a clinical version of damage to cholinergic neurons which is part
      of the selective pathology of Alzheimer's disease. In general, CNS neurons do not
      regenerate well after brain damage. The first part of the review describes how
      the CNS promotes only limited neuronal regeneration, and that this is because of
      the presence of inhibitory factors and the lack of growth factors. Despite this,
      some CNS areas may provide a better environment for CNS regeneration than others.
      In the second part of the review, the degeneration and regeneration of basal
      forebrain cholinergic pathways in the adult rat are discussed. It is shown how
      the collateral sprouting of cholinergic axons occur more readily in the
      hippocampal formation than in neocortical areas, and that this could be linked
      with the more neuroplastic properties of the hippocampus. The third part of the
      review describes how the degeneration of cholinergic pathways in Alzheimer's
      disease is likely to be secondary to the pathology or degeneration of certain
      cortical areas. The hypothesis is put forward that the severity of the pathology
      in highly plastic limbic cortical areas could be linked with their susceptibility
      to risk factors of Alzheimer's disease such as ageing, and genetic and
      environmental factors.

PMID- 8735879
TI  - Endothelial cells of the brain and other organ systems: some similarities and
      differences.
AB  - The cerebral endothelium represents an active interface between blood and central
      nervous system. The blood-brain barrier restricts the free passage of nutrients,
      hormones, drugs and cellular elements to the brain. Recent studies performed on
      freshly isolated cerebral microvessels and cultured endothelial cells of brain
      capillaries provided a better understanding of the properties and functions of
      cerebral endothelial cells. This review summarizes the main findings of the in
      vitro approach in the blood-brain barrier research, describes the common
      endothelial and unique cerebral features of the brain endothelium, and provides a
      short overview on how these blood-brain barrier characteristics can be induced in
      cerebral endothelial cells by the neighbouring cells.

PMID- 8735880
TI  - Deleterious network hypothesis of Alzheimer's disease.
AB  - Numerous studies indicate that aberrant amyloid precursor protein metabolism,
      elevated peroxidative damage, depressed energy metabolism and altered calcium
      homeostasis are four pivotal deleterious factors in the pathogenesis of
      Alzheimer's disease. Cumulative evidence further suggests that these four factors
      are intimately interrelated, forming a deleterious network. Based on this new
      concept of 'deleterious network', a unifying hypothesis-the deleterious network
      hypothesis of Alzheimer's disease-is proposed. The main ideas of the hypothesis
      are delineated as follows: increases in free radical damage, alterations in
      amyloid precursor protein metabolism, impairment of energy metabolism and
      abnormalities of calcium homeostasis are four cornerstones of a deleterious
      network. Various risk factors of Alzheimer's disease can triger the network by
      promoting the occurrence of one of these key components, resulting in the
      biological abnormalities of Alzheimer's disease. Based on this new theory, a
      majority of the important observations about Alzheimer's disease can be explained
      consistently and succinctly.

PMID- 8735881
TI  - The UK epidemic of BSE: slow virus or chronic pesticide-initiated modification of
      the prion protein? Part 1: Mechanisms for a chemically induced
      pathogenesis/transmissibility.
AB  - It is proposed that exposure of the bovine embryo to specific high-dose
      lipophilic formulations of organophosphate insecticide (containing phthalimide)
      applied exclusively in the UK during the 1980s/early 1990s was the primary
      trigger that initiated the UK's bovine spongioform encephalopathy epidemic. Multi
      site binding organophosphate toxic metabolites penetrate the fetus, covalently
      binding with, phosphorylating and ageing serine, tyrosine or histidine active
      sites on fetal central nervous system prion protein. An abnormal negative charge
      corrupts prion protein molecular surface, which blocks both proteases and
      chaperones from accessing their cleavage/bonding sites. This impairs normal
      degradation and folding of prion protein respectively. Once the abnormally
      phosphorylated abnormal prion protein isoform agent is initiated, any stress
      event ensuing in adult life induces a nerve growth factor-mediated synthesis of
      normal cellular prion protein isoform that aggregates to abnormally
      phosphorylated abnormal prion protein isoform, thereby becoming
      'infected'/transformed into the same; due to the vicious circle of positive
      feedback invoked by the blocking of a prion protein-specific kinase. Prion
      protein could therefore serve as a hitherto unrecognized critical link in a chain
      of delayed neuroexcitotoxic proteins that are triggered off by chronic exposure
      to specific classes of chemical/metal that 'hit and run' during the vulnerable in
      utero period, producing spongioform encephalopathy disease years later.

PMID- 8735882
TI  - The UK epidemic of BSE: slow virus or chronic pesticide-initiated modification of
      the prion protein? Part 2: An epidemiological perspective.
AB  - This paper elucidates the flaws in the official hypothesis that bovine
      spongioform encephalopathy originated from alterations in the way that scrapie
      contaminated cattlefeeds were manufactured in the UK. An alternative hypothesis
      is proposed that cites exposure of the bovine embryo to various specific high
      dose lipophilic formulations of organophosphates, such as the high-dose
      phthalimide containing organophosphate phosmet, (which were applied compulsorily
      and exclusively in the UK during the 1980s/early 1990s) as the primary trigger
      that initiated the deformation of prion protein and the onset of the bovine
      spongioform encephalopathy epidemic. The multi-site binding metabolites of these
      organophosphates penetrate the fetus, covalently phosphorylating various active
      sites on fetal prion protein. The extra charged phosphate groups left on aged
      prion protein blocks both proteases and chaperones from accessing their
      catalytic/bonding sites, creating the undergradable, misfolded isoform of prion
      protein, PrPsc. The resulting abnormally phosphorylated PrPsc aggregates to
      freshly synthesized PrPc, transforming it into same; due to a system of positive
      feedback invoked by the organophosphate-induced blockage of a prion protein
      specific protein kinase. Both the timing, distribution and dynamics of usage of
      these specific organophosphates correlates with the epidemiology of bovine
      spongioform encephalopathy as well as accounting for the 23,000 cattle that have
      developed the disease, yet were born after the 1988 ban on scrapie-contaminated
      cattlefeed.

PMID- 8735883
TI  - The potential role of apoptosis (programmed cell death) in a chaotic determined
      carcinogenesis.
AB  - The proposed hypothesis may interpret apoptosis as a dynamic parameter by means
      of chaos theory. Regular tissue renewal is determined by the quantity of mitosis
      and cell death (mainly apoptosis). These two components are describable as so
      called 'limit cycle attractor' representing a reference cycle of the tissue
      system. If tissue kinetics remain within these limits, the system stays in a
      homeostatic equilibrium. Disruptive factors such as genetic alterations may have
      the ability to destabilize this homeostasis and induce the quasiperiodic
      development which represents one way in which a system becomes chaotic. The
      inhibition of apoptosis prevents the elimination of mutation-affected cells which
      leads to an uncoordinated proliferation of a mutated cell clone. Thus, this clone
      represents an independent oscillator which effects a new attractor: it is called
      'torus' attractor. Additional perturbations induce the chaotic 'strange
      attractor': the system is bound to shift into chaos, morphologically detectable
      as cancer.

PMID- 8735884
TI  - Cancer and malignant resistance of cells as phenomena of adaptation to damaging
      factors.
AB  - I propose the hypothesis that mechanisms of general biological persistent
      resistance to damaging factors are closely related to the development of tumour
      cells. This phenomenon is characteristic of bacterial variants whose resistance
      to antibiotics and other chemotherapeutic drugs appears through L-transformation.
      As somatic cells are exposed to carcinogens and develop into tumour cells, they
      also acquire resistance to the toxic effects of carcinogens through multistage
      malignant transformation. Many cancerous cells, which have acquired persistent
      resistance to chemotherapy drugs or irradiation, often reappear locally or in
      metastases after courses of treatment. Thus, these cells undergo a kind of
      repeated development of malignancy. After a certain remission period, they begin
      to multiply more intensively locally, and are more likely to spread by
      metastasis. All resistant cells have the following characteristics: simplified
      metabolism, genetic, biochemical and morphological properties; lower requirements
      from their nutrient medium; rapid growth; parasitic qualities; invasiveness. It
      is as if they regress into a more primitive mode of existence (atavism) to
      survive under unfavourable circumstances. Somatic cells, resistant to carcinogens
      and the cells which undergo progression to more malignant types under the
      influence of drugs become similar to unicellular organisms or to forms of the
      latter which are resistant to damaging factors. The more primitive the cells
      become, the better they survive. Thus, cancer is a special case of the general
      resistance of cells to damaging factors.

PMID- 8735885
TI  - The physiology of boredom, depression and senile dementia.
AB  - Mental stimulation ensures the flow of blood, oxygen and nutrients to the brain.
      The stimulation can be either generated internally from thought and rumination or
      externally from our environment via the senses. Without this stimulation, neuron
      shrinkage and atrophy eventually may lead to depression and senile dementia. This
      paper explains why mental stimulation may be prevented from realizing its
      beneficial effects of increasing the blood flow to the brain. The hypothesis is
      based on feedback biological mechanisms that prevent overload of the neural
      circuitry due to excessive mental stimulation. However, if overstimulation is
      maintained over a long period and, with it, the overload protection process, it
      may eventually lead to permanent depletion of neuron connections and also neural
      communications.

PMID- 8735886
TI  - Scientific productivity of Einstein, Freud and Landsteiner.
AB  - The scientific productivity of Albert Einstein was compared to that of designated
      controls Karl Landsteiner (an experimental scientist) and Sigmund Freud (an
      eminent theorist). Three assumptions made for this comparison were (1) that
      Einstein and his designated controls had equal scientific stature; (2) that their
      publications were produced in a similar, if not identical, sociocultural milieu;
      and (3) the number of publications is directly proportional to scientific
      productivity. At the end of their illustrious careers, Einstein, Freud and
      Landsteiner accumulated 315, 320 and 345 scientific publications respectively.
      Einstein was the sole author in 88% of his publications, which validates the
      third assumption. Thus, one can conclude that quantitative comparison of
      Einstein's total scientific publications with that of appropriate controls such
      as Landsteiner and Freud shows that Einstein's chronic ill health did not
      influence his scientific productivity.

PMID- 8735887
TI  - Adrenocorticotropin--a central trigger in immune responsiveness: tonal inhibition
      of immune activation.
AB  - Adrenocorticotropin is known for its key role in mediating neuroendocrine
      responses, especially in response to stress. Recently, it has been recognized to
      have direct immunomodulatory actions, most of which are suppressive. This is a
      widely conserved action which occurs in invertebrates and vertebrates. This
      conservation illustrates the fundamental nature of adrenocorticotropin's
      immunomodulatory action. Such a mechanism of action helps explain why the
      immunocytes themselves can serve as a source of adrenocorticotropin. Regulation
      of adrenocorticotropin production and action is complex and the result is an
      integration of multiple mechanisms. Serum adrenocorticotropin levels fluctuate in
      response to stimulatory and inhibitory factors. Further, peptidases can
      specifically process adrenocorticotropin into smaller active fragments, inactive
      peptides or into peptides with different activities. These proteolytic enzymes
      have a differential tissue and cellular distribution. Immune stimulating factors
      such as interleukin-1 can overcome adrenocorticotropin inhibition and
      secondarily, block adrenocorticotropin production through the release of
      corticosteroids. With an endogenous presence and complex regulation it has been
      difficult to characterize adrenocorticotropin's role in the immune system. Here,
      we propose that adrenocorticotropin is a tonis regulator of immune response, i.e.
      it tonally inhibits immunocytes which undergo disinhibition as the result of
      exposure to stimulatory signals, e.g. cytokines, neuropeptides, etc. Thus,
      adrenocorticotropin appears to set the threshold for immunoactivation by
      controlling the degree of immunoexcitability.

PMID- 8735888
TI  - Central origin of decreased heart rate variability in patients with
      cardiovascular diseases.
AB  - Sympathetic activity influences the total power of the heart rate variability
      spectrum. Decreased heart rate variability and increased sympathetic tone have
      been related to poor prognosis and an increased risk of sudden cardiac death in
      patients with myocardial infarction, congestive heart failure or hypertension. On
      the basis of recent experimental data, I propose that these disease states are
      associated with altered spectral characteristics of the central sympathetic
      activity generated within rostral ventrolateral medulla neurones, which
      subsequently leads to decreased heart rate variability and increased systemic
      sympathetic tone.

PMID- 8735889
TI  - Breast cancer: a significant causal relationship.
AB  - It has been reported that the stimulation of travelling in a motor vehicle
      triggers abnormal hormonal and adrenal excretion and also abnormal changes in the
      body's fuel system. Figures presented in this paper suggest that motor vehicle
      travel may be important in breast cancer deaths.

PMID- 8735890
TI  - Short note: on the unpleasantness of certain harsh sounds.

PMID- 8735891
TI  - Women & health policy in developing countries.

PMID- 8735892
TI  - Psychosocial factors of coronary heart disease in women: a review.
AB  - Although coronary heart disease is the leading cause of death in women in most
      industrialized countries, much less research has been carried out on this topic
      to date than in men. This article gives an overview of psychosocial factors of
      coronary heart disease in women, focussing on psychosocial risk factors for
      coronary heart disease in women such as socioeconomic status, employment status,
      chronic troubling emotions, social support and bereavement/widowhood. A second
      focus lies on psychosocial adjustment in women once coronary heart disease has
      become manifest, i.e. well-being, return to work, sexual activity and
      rehabilitation outcome after a myocardial infarction or coronary artery bypass
      grafting. Via a computerized literature research in Medline, Psychlit and
      Sociofile over the period 1980-1994 all studies on these topics were collected
      and reviewed. Comparatively more research has been undertaken on psychosocial
      risk factors for than on psychosocial adjustment to coronary heart disease in
      women. Low social class, low educational attainment, the double loads of work and
      family, chronic troubling emotions and lack of social support emerge as
      documented risk factors in women. Regarding psychosocial adjustment to coronary
      heart disease in women, there is a paucity of data, and studies including large
      samples of women and adjusting for gender are warranted. Psychosocial adjustment
      in women after a myocardial infarction seems to be worse than in men, whereas
      results on adjustment after coronary artery bypass grafting are inconclusive.
      Return to work rates after myocardial infarction or coronary artery bypass
      grafting are significantly lower in women than in men. Data on sexual activity of
      women after myocardial infarction or coronary artery bypass grafting are scarce,
      and there seems to be a complete lack of physician counseling on this topic.
      Studies on rehabilitation outcome report poorer programme uptake, poorer
      adherence and significantly higher drop-out rates for women than for men, yet
      those women who complete cardiac rehabilitation show the same or even greater
      functional improvements than men.

PMID- 8735893
TI  - Women, health and the environment.
AB  - This paper develops a conceptual framework for gender-sensitive research and
      policy analysis that centres on women's interaction with the biophysical
      environment, and the implications of that interaction for their environmental
      health. The paper reviews the lack of data on women's non-reproductive health,
      and argues that there is a need for increased research and policy formulation
      dealing with women's environmental health in both the developing and the
      developed countries. One important dilemma for most researchers interested in
      women's environmental health is the lack of an appropriate conceptual model. The
      paper argues that attention to women's interaction with the biophysical
      environment within their own life spaces' reveals that women are exposed to the
      hazards of environmental illness in a manner that is clearly gender
      differentiated. The paper reviews the impact of poverty, illiteracy and gender
      bias on women's life spaces, and argues that the failure to recognize and protect
      women's life spaces in economic policy and planning commonly leads to "disease
      environments" for women and their children. Evidence of the impact of such
      disease environments on women's environmental health is drawn from the urban
      setting and from women's experience of desertification in Africa and Asia. The
      paper reviews the policy issues that emerge from this analysis, and makes a
      series of suggestions for national and international policy and action in support
      of improvements in women's environmental health.

PMID- 8735894
TI  - Maternal mortality and the problem of accessibility to obstetric care; the
      strategy of maternity waiting homes.
AB  - One of the major causes of maternal mortality is the distance and consequent
      delay in treatment of childbirth complications. Some developing countries are
      attempting to reduce delays in treatment by moving women at risk into maternity
      waiting homes (MWHs), located near a hospital, a few days prior to the date of
      confinement. This paper illustrates some typical examples of MWHs in different
      countries. The approach of MWHs is appropriate in some settings but it requires a
      high degree of coordination between peripheral prenatal care services and second
      and third level health care facilities. This study discusses some of the issues
      related to the successful functioning of MWHs, and provides an analytical
      framework for the planning, management and evaluation of these facilities.

PMID- 8735896
TI  - Lymphatic filariasis and the women of India.
AB  - Lymphatic filariasis is a disease of the poor and underprivileged and has
      received little attention in the past. In particular, there has been a lack of
      gender sensitive research on women and lymphatic filariasis. Women suffer from
      lymphatic filariasis to a great extent but embarrassment, shame, cultural
      constraints and social taboos are some of the reasons that refrain them from
      reporting problems and seeking help. Women are thus silently bearing the brunt of
      this disease. This study has tried to obtain basic information on women and
      lymphatic filariasis with a gender approach. To understand the consequence of
      lymphatic filariasis on women in India, a holistic framework was used for this
      study, which encompasses all issues in women's lives such as their perspective on
      the disease, their role as social and economic entities and their relationships
      with others; in addition to their reproductive role. A qualitative approach using
      the technique of informal interview was used for this research. Eighty-eight
      women and 39 children were interviewed, during home visits and at clinics,
      primary health care centers and schools in both urban and rural areas in India.
      The study has obtained the much needed information on the knowledge of lymphatic
      filariasis among women in India, the impact of the disease on the women which
      include the social and economic aspects, clinic attendance and the barriers to
      health care for women with the disease, and women's awareness regarding control
      programs for lymphatic filariasis. The study also found how women cope with the
      disabilities or other manifestations of the disease. This paper discusses
      lymphatic filariasis using a gender sensitive approach. It reviews the
      literature, describes the study, analyzes the results and suggests feasible
      disease control programs for women with a multisectoral approach.

PMID- 8735895
TI  - Chinese village women as visual anthropologists: a participatory approach to
      reaching policymakers.
AB  - In developing countries, rural women are often neither seen nor heard, despite
      their extraordinary contribution to the labor force. Photo novella is an
      innovative methodology that puts cameras in the hands of rural women and other
      constituents who seldom have access to those who make decisions over their lives.
      As an educational tool, the practice of photo novella has three main goals: (1)
      to empower rural women to record and reflect their lives, especially health
      needs, from their own point of view; (2) to increase their collective knowledge
      about women's health status; and (3) to inform policymakers and the broader
      society about health and community issues that are of greatest concern to rural
      women. In this paper we analyze the third goal: the contributions and limitations
      of photo novella as a tool for informing policymakers. We conceptualize first the
      theoretical and practical underpinnings of photo novella. After tracing the
      relationships among empowerment education, feminist theory, documentary
      photography and policy, we describe photo novella within the broader context of
      the Ford Foundation-supported Yunnan Women's Health and Development Program and
      explain its application for influencing policy based on our experience carrying
      out photo novella in China.

PMID- 8735897
TI  - Working women's sexual risk taking in Jamaica.
AB  - Although the rates of HIV are increasing among female populations in developing
      countries, there is little information available about factors influencing sexual
      risk taking among working class women. This paper describes some of the issues
      discussed by two groups of 58 women working in Jamaica: Informal Commercial
      Importers and women working in the Freezone. These women discuss their economic
      vulnerability, expectations about the role of men as providers, multiple
      partners, perceptions of children as resources and concern about physical abuse
      as factors that could influence decisions about condom use. The implications of
      these findings are discussed for their impact on intervention programs targeting
      working class women in Jamaica.

PMID- 8735898
TI  - Medical professional dominance and client dissatisfaction. A study of doctor
      patient interaction and reported dissatisfaction with medical care among female
      patients at four hospitals in Trinidad and Tobago.
AB  - The aims of the study were to evaluate the presence of 'medical professional
      dominance' displayed by physicians, and to assess the levels of satisfaction with
      care received, as reported by a simple random sample of 320 patients on obstetric
      and gynaecology wards at four hospitals in Trinidad and Tobago. Professional
      Dominance was defined entirely in relation to quality of doctor-patient
      interaction, while patient satisfaction levels were reported measures. Two
      methods were used in the study: participant observation techniques were employed
      to obtain data on doctor-patient interaction, and the survey interview method was
      used for assessing levels of satisfaction of patients with care received. The
      results showed disturbingly high levels of both medical professional dominance
      and patient dissatisfaction. The results of similar studies carried out in the
      U.S.A. and Britain were used to draw a causative relationship between medical
      professional dominance and patient dissatisfaction.

PMID- 8735899
TI  - The provision of female sterilization in Sao Paulo, Brazil: a study among low
      income women.
AB  - This paper examines some problems involved in the provision of female
      sterilization procedures in Brazil, mainly those concerned with the ways in which
      this operation is offered. Female sterilization provision is analysed by
      reference to the broader institutional context and from the client's
      perspectives. These themes are discussed in the light of some recent survey
      findings. A survey was carried out between March and July, 1992 in two selected
      poor areas of Sao Paulo Metropolitan Region. 3149 women were asked about
      contraceptive use including 407 sterilized women under 40 years old who were also
      interviewed about their adaptation to sterilization. Further information was also
      obtained through in-depth interviews with 15 sterilized women who regretted the
      operation. The findings highlight a complex network of interests and
      misunderstandings which shape the nature of choice of female sterilization by
      Brazilian low income women.

PMID- 8735900
TI  - Gender aspects and women's participation in the control and management of malaria
      in central Sudan.
AB  - This work was designed to study the contribution of women in central Sudan in the
      control and management of malaria with particular emphasis on gender-related
      aspects that define women's role and participation. The Blue Nile Health Project
      (BNHP 1980-1990) was launched in 1980 mainly for control of water associated
      diseases in central Sudan. The BNHP model was chosen to conduct this work. The
      study showed that women were actively involved in the implementation of the BNHP
      strategies as health instructors (murshidat) who constituted 75% of the staff of
      BNHP unit of health education, as members of village health committees (VHC)
      where they constituted 40% of the VHC members and also as recipients of the
      project services. All murshidat were interviewed whereas multistage random
      sampling for VHC members and recipient women in 40 villages was used to select a
      sample which was interviewed. The results showed that the murshidat and VHC women
      members played a major role in the motivation, organization and health education
      of local communities prior to campaigns of environmental sanitation and vector
      control. Household commitments and difficulties in communication with the public
      were the main gender-related factors that contributed negatively to women's
      activities. Cases of malaria have more considerable socio-economic impact than
      other common diseases, especially with regard to women's household commitments
      and work. Recipient women were more concerned with aspects of self protection,
      management of family cases of malaria and health education programmes. They were
      less involved in drying mosquito breeding sites and spraying activities of
      insecticides which had been reluctantly accepted because of allergy and bad
      odour. Although the majority of women considered antimalarials to be less harmful
      than effects of malaria itself on pregnancy, they did not realize the role of
      malaria chemoprophylaxis during pregnancy. This needs more health education. The
      study showed that the BNHP programme was very successful in recruiting women in
      control and management programmes. Therefore, health planners are urged to
      persuade the subordinated communities of women in many African countries like
      Sudan to play a more active role in the health programmes and welfare of their
      communities.

PMID- 8735901
TI  - The menopause: women's psychology and health care.
AB  - Menopause has often been described as a time of loss and decay in the lay and
      medical literature. The present research aims at defining women's perception of
      themselves and their health care needs in this period of life. Through a
      community-based sample of women, participative assessments were performed and
      their conclusions contrasted with the opinions of male and female gynecologists.
      Though both groups coincided concerning the relevance of loneliness, partnership,
      beauty and the "empty nest" syndrome, several items showed a marked difference
      between both groups. Gynecologists tended to perceive women as much more striving
      for an active sex-life, depressed, lacking projects for the future and worried
      about their health care than they actually were. Women, instead, stressed the
      relevance of menopause as a life crisis laden with opportunities for self
      accomplishment and positive changes in life-style towards greater autonomy.

PMID- 8735902
TI  - Evaluation of patterns of urinary proteins by SDS-PAGE in rats of different ages.
AB  - The patterns of urinary proteins in rats of different ages were examined on SDS
      gradient polyacrylamide gel electrophoresis coupled with silver staining.
      Proteins were fractionated into at least 26 bands. Densitometric measurements
      were used to characterize protein excretion patterns. The results showed that
      proteinuria in newborn, young and adult rats is predominantly tubular, consisting
      of low molecular-weight species. Conversely, late adults and old rats had a mixed
      glomerular pattern, with a steadily increasing excretion of albumin, IgG and
      transferrin, as was the case of other high molecular-weight proteins. Fragments
      of both immunoglobulins and albumin were found in all urine samples assayed. In 1
      month old rats the percentage of Tamm-Horsfall (T-H) protein was higher (P <
      0.01) than in the remaining groups studied. In newborns, relatively high albumin,
      IgG and transferrin percentages were detected, as well as an alpha 1-acid
      glycoprotein and carbonic anhydrase excretion (P < 0.05 and P < 0.01
      respectively) higher than that observed in the other age groups studied.

PMID- 8735903
TI  - Food restriction increases the protection of erythrocytes against the hemolysis
      induced by peroxyl radicals.
AB  - We have investigated the susceptibility to peroxidation of erythrocytes from
      young, adult and old ad libitum (AL) fed, as well as from adult and old food
      restricted rats, measuring the rate of hemolysis under controlled peroxidative
      condition. Food restriction has been applied on an every-other-day (EOD) schedule
      starting from the age of 3.5 months. The oxidation of red blood cells by
      molecular oxygen was performed in an aqueous suspension using the azo-compound 2
      2'-azo-bis-(2-amidinopropane)hydrochloride (AAPH) as the free radical initiator.
      Several parameters were calculated from the time-dependent curve of AAPH induced
      hemolysis. The time required to achieve 50% hemolysis decreased with aging and
      this decrease was prevented by food restriction. The lag time, which reflects the
      capacity of the cell to buffer free radicals, was longer in young than in old AL
      fed animals also this impairment was almost completely prevented in EOD fed
      animals. The same beneficial effect of food restriction was observed considering
      the maximal amount of hemolysis attained with the dose of AAPH applied and the
      time necessary to reach this level. The general picture emerging from the present
      study is that erythrocyte membranes from EOD fed rats are better protected, than
      those from AL fed ones, against damages caused by peroxidation. This effect may
      be due to a difference in the chemical composition of the erythrocyte membranes
      as it was found in other organs.

PMID- 8735904
TI  - Short-term caloric restriction augments age-related decreases in gastrin content
      and release.
AB  - Aging is associated with significant structural and functional changes in the
      gastrointestinal tract. Gastrin, a hormone produced by G cells in the antrum of
      the stomach, stimulates proliferation of gastric mucosa; its synthesis appears to
      decrease with age. Life-long restriction of caloric intake is the only
      experimental manipulation that has been shown to retard aging processes in rats.
      The purpose of this study was to examine the effect of short-term caloric
      restriction (CR) on the production and release of the hormone gastrin with aging.
      Aging causes a fall in both fasting plasma levels of gastrin and antral content
      of gastrin in Fischer 344 rats; short-term CR appears to augment this age-related
      decrease. Steady state levels of antral gastrin mRNA were decreased with aging,
      and short-term CR resulted in an augmented decrease in aged, but not in young
      rats. Our findings indicate that gastrin release, synthesis and gene expression
      decrease with age. Restriction of the caloric intake for a short period (i.e. 8
      weeks) augments this age-related decrease in antral gastrin and fasting plasma
      levels. Short-term CR appears to decrease the production of gastrin at the level
      of gene expression.

PMID- 8735905
TI  - Mitochondrial electron transport chain activities and DNA deletions in regions of
      the rat brain.
AB  - Deletions in human mitochondrial DNA cause various mitochondrial myopathies and
      increase markedly with age in highly oxidative tissues, but exhibit a
      differential distribution in the brain. In order to determine whether a similar
      pattern occurs in rat brain the levels of a 4.8 kb deletion and electron
      transport complex activities were measured in the striatum, hippocampus,
      cerebellum, and cerebral cortex of young adult and senescent male Wistar rats.
      Deletion-containing mtDNA was present at relatively similar levels (0.0003%) in
      all regions in 6 mo rats, but increased 25-, 7-, 3-, and 2-fold in the striatum,
      hippocampus, cerebral cortex, and cerebellum, respectively, of 22-23 mo old rats.
      To assess the relationship between fractional occurrence of a deletion and
      oxidative phosphorylation capacity, the activities of mitochondrial respiratory
      chain complexes I, III, IV and V, the mitochondrial ATP-ase, each of which
      contains subunits encoded in mtDNA, were determined in homogenates. No age
      related decrements in activity were observed in any of the brain regions. Thus,
      while mtDNA deletions increase with age and to a large extent mirror the pattern
      observed in the human brain, they appear to have no effect on capacity for
      oxidative phosphorylation of distinct brain regions. Any reductions in capacity
      that may be present are likely to occur only at the level of individual cells.

PMID- 8735907
TI  - On the causation of animal morphogenesis: concepts of German-speaking authors
      from Theodor Schwann (1839) to Richard Goldschmidt (1927).

PMID- 8735906
TI  - In vitro senescence enhances IL-6 production in human gingival fibroblasts
      induced by lipopolysaccharide from Campylobacter rectus.
AB  - The production of interleukin-6 (IL-6) in human gingival fibroblasts (Gin cells)
      is increased by lipopolysaccharide (LPS) from Campylobacter rectus (C. rectus),
      which is associated with adult periodontitis; however, the age-related changes in
      the susceptibility of Gin cells to C. rectus LPS remain unclear. We examined the
      influence of in vitro senescence on C. rectus LPS-stimulated IL-6 production in
      Gin cells. LPS was prepared from C. rectus ATCC 33238 using hot phenol-water. The
      Gin cells were established from healthy gingival tissue removed from three
      patients, aged 10-12 years. The cells were cultured until confluence then
      stimulated with LPS (0.01, 0.1, 1.0 and 10.0 micrograms/ml). Levels of IL-6
      released in the medium were measured after incubation for 3, 6, 9, 12, and 24 h.
      In both young (5-6 population doublings) and senescent (17-20 population
      doublings) cells, LPS stimulated IL-6 production in a dose- and time-dependent
      manner. In response to 0.01-10.0 micrograms/ml of LPS, IL-6 production in the
      senescent cells was higher than that in the young cells. Using cells from each of
      the three donors, we found that this phenomenon of higher LPS-stimulated IL-6
      production in senescent cells was reproducible. The greater capacity of the
      senescent cells to synthesize IL-6 in response to LPS was a higher production of
      mRNA for IL-6. This increase of IL-6 production induced by C. rectus LPS in
      senescent Gin cells could help to explain the increased susceptibility to
      periodontal diseases shown by aged individuals.

PMID- 8735909
TI  - Boveri's contributions to developmental biology--a challenge for today.

PMID- 8735910
TI  - Hans Spemann (1869-1941) and the Freiburg School of Embryology.

PMID- 8735908
TI  - From the Aristotelian soul to genetic and epigenetic information: the evolution
      of the modern concepts in developmental biology at the turn of the century.

PMID- 8735912
TI  - The impact of Spemann's concepts on molecular embryology.

PMID- 8735911
TI  - Memories of Professor Hans Spemann's Department of Zoology at the University of
      Freiburg, 1920-1932.

PMID- 8735913
TI  - Alfred Kuhn, his work and his contribution to molecular biology.

PMID- 8735915
TI  - Genes and development: an early chapter in German developmental biology.

PMID- 8735914
TI  - Morphogenesis, Seidel's legacy for developmental biology and challenge for
      molecular embryologists.

PMID- 8735916
TI  - The origin of developmental physiology of plants in Germany.

PMID- 8735917
TI  - On the hormonal control of insect metamorphosis. A historical review.

PMID- 8735918
TI  - Sea urchin embryology in the sixties.

PMID- 8735919
TI  - The impact of the Zoological Station in Naples on developmental physiology.

PMID- 8735920
TI  - The long road to chemical and molecular embryology. What amphibians can teach us
      on differentiation. An interview with Professor Heinz Tiedemann. Interview by
      Horst Grunz.

PMID- 8735921
TI  - Models of biological pattern formation: common mechanism in plant and animal
      development.
AB  - Earlier proposed models for primary pattern formation, for gene activation and
      for segmentation are summarized and compared with recent molecular-genetic
      observations. A model for head, foot, tentacle and bud formation in Hydra
      illustrates that complex patterns can be reliably generated. Stable cell
      determination requires autocatalytic (autoregulatory) genes. Segmentation in
      insects has been proposed to result from a reiteration of (at least three) cell
      states. Their patterning is achieved by a mutual activation of cell states that
      locally exclude each other. A model for accretion of new segments by
      proliferation at the posterior pole is proposed that accounts for the generation
      of a periodic and a sequential pattern in register with each other. The
      assumption of a process analogous to segmentation in plants can account for the
      initiation of leaves with an intrinsic polarity that eventually leads to the
      upper and lower leaf surfaces. The model accounts also for the formation of
      axillary buds in correct relation to a leaf and for the much smaller spacing of
      leaves within a whorl when compared with the spacing between two successive
      whorls along the shoot. It is concluded that the generation of complex structures
      in distantly related organisms may be based on similar mechanisms.

PMID- 8735923
TI  - Macronucleus structure and macronucleus development in hypotrichous ciliates.
AB  - In the course of macronuclear development of the hypotrichous ciliates all
      genetic information not required for normal growth of the cell is removed from
      the new macronucleus. This differentiation process involves DNA-splicing,
      excision of transposons, DNA-fragmentation, selective gene amplification and
      telomere addition. Since many of the processes observed during macronuclear
      development, such as DNA-transposition, DNA-rearrangement or selective DNA
      amplification, may occur in differentiating cells of higher organisms, this
      biological system provides an unusual opportunity to study the ways in which DNA
      sequences can be manipulated in a differentiating cell.

PMID- 8735922
TI  - On the role of calcium during chemotactic signalling and differentiation of the
      cellular slime mould Dictyostelium discoideum.
AB  - Transient cytosolic calcium elevations are required for chemotaxis and
      differentiation of Dictyostelium discoideum since Ca2+ chelating buffers
      introduced into the cells by scrape loading inhibited motility as well as
      orientation in a Ca2+ specific manner. Ca2+ changes are provided either by
      intrinsic cytosolic Ca2+ oscillations that can be determined as periodic Ca2+
      efflux, or by receptor-mediated Ca2+ liberation from the InsP3-sensitive store
      and Ca2+ influx. Cytosolic Ca2+ homeostasis as well as oscillations seem to be
      regulated by two different Ca2+ stores, the acidosomes and the InsP3-sensitive
      store, both of which are dependent on Ca2+ pumps and V-type H+ ATPases. Ca2+
      transients are sensed by calmodulin-binding proteins. The latter have been
      detected in Dictyostelium by 125I-calmodulin labeling. A calmodulin-dependent
      protein phosphatase, calcineurin A, was cloned, sequenced, purified and
      characterized biochemically. Overproduction of calcineurin A as well as antisense
      constructs will help to the elucidation of its function in signal transduction.
      Surprisingly, protein synthesis is also controlled by Ca2+/calmodulin. An
      integral ribosomal protein of the 60S subunit, L19, proved to be a calmodulin
      binding protein and calmodulin antagonists of different classes, inhibited in
      vitro translation of Dictyostelium and wheat germ extracts.

PMID- 8735924
TI  - Drosophila differentiation genes instrumental in tumor suppression.
AB  - Tumor suppressor genes of Drosophila are developmental genes which, in the
      homozygously mutated state, induce in one step malignant or benign neoplastic
      transformation of specific cell types. They act early in development and by this
      set the stage for cell specific differentiation of imaginal discs, adult optic
      neuroblasts, blood and gonial cells. The structure, expression and possible
      function of the following four tumor suppressor genes are discussed: tumorous
      imaginal disc, lethal (3) malignant brain tumor, lethal (3) malignant blood
      neoplasm-1 and benign (2) gonial cell neoplasm.

PMID- 8735925
TI  - Regulation and function of the terminal gap gene huckebein in the Drosophila
      blastoderm.
AB  - Pattern formation in Drosophila involves a cascade of maternal and zygotic
      factors which are spatially restricted in the blastoderm embryo. Here we show
      that the Drosophila gene huckebein (hkb), a member of the gap gene class of
      segmentation genes, is not only required for suppression of segmentation in the
      terminal regions of the embryo but also to spatially restrict germ layer
      formation at the beginning of gastrulation. hkb encodes a Sp1/egr-like zinc
      finger protein, likely to be a transcription factor. Its absence in hkb mutants
      causes the ectodermal and mesodermal primordia to expand at the expense of
      endoderm anlagen, which are completely absent in null alleles of hkb. Conversely,
      ectopic expression of hkb inhibits the formation of the major gastrulation fold
      which gives rise to the mesoderm and prevents normal segmentation in the ectoderm
      of the trunk region.

PMID- 8735926
TI  - Spermatogenesis in Drosophila.
AB  - A short summary on the present knowledge on spermatogenesis in Drosophila is
      given which also points out particular questions of interest in the context of
      this morphogenetic process. Such points of interest are the formation of
      lampbrush loops in primary spermatocytes, the chromosomal events during meiosis,
      the occurrence of chromatin rearrangements and the regulation of gene activities
      at the posttranscriptional level. The activities and some major conclusions from
      my laboratory are subsequently described. They include studies of the expression
      of histone variants, the structure and function of lampbrush loops and the
      expression of genes participating in sperm morphogenesis.

PMID- 8735927
TI  - Structural and functional properties of linker histones and high mobility group
      proteins in polytene chromosomes.
AB  - Variants of histone H1 and high mobility group (HMG) proteins and their genes in
      Dipteran insects are being studied in our laboratory and have revealed different
      properties of DNA binding and intrachromosomal distribution. One of the H1
      variants of Chironomus is found only in a minority of polytene chromosome bands
      and differs from the other H1 proteins of the same organism by genomic
      organization and by an inserted structural motif, the KAPKAP repeat, that is
      present also in single H1 variants of other, evolutionarily remote organisms. NH2
      terminal peptides containing the KAPKAP repeat were found in vitro to interact
      with DNA, whereas no DNA interaction was observed with the homologous peptide of
      another H1 variant that does not contain the inserted KAPKAP repeat. We assume
      that H1 variants containing the KAP motif may interact with a stretch of linker
      DNA and package chromatin more tightly than other H1 variants. A large series of
      antibodies directed against different sites in all regions of the H1 molecule is
      being applied in studying the sites of interaction of the H1 molecule with other
      molecules in interphase chromatin in terms of antibody epitope accessibility. A
      search for insect proteins that share properties of the mammalian HMG proteins
      resulted in isolation and sequencing of two different HMG1 proteins and an HMGI
      protein. The HMG1 protein of the midge, Chironomus tentans, show a differential
      distribution in chromosomes. The more abundant cHMG1a protein appears uniformly
      distributed, whereas the less abundant cHMG1b protein could be localized only in
      chromosomal puffs. This strongly indicates that these highly similar proteins
      have different functions in chromatin. The Chironomus HMGI protein and the
      intron/exon organization of its gene were found to be very similar to human
      HMGI/Y proteins that are highly abundant in rapidly proliferating cells. Common
      properties of HMG1 and HMGI proteins include high affinity interaction with AT
      rich DNA, irregular DNA structures, and the capacity to bend DNA. These
      properties suggest that the HMG proteins may have an architectural role in
      assembling different types of chromatin.

PMID- 8735928
TI  - Muscle development and attachment to the epidermis is accompanied by expression
      of beta 3 and beta 1 tubulin isotypes, respectively.
AB  - In Drosophila beta tubulins are encoded by a small gene family whose members are
      differentially expressed in a highly cell and tissue specific manner. Here we
      focus on the expression of the beta 3 tubulin isotype during mesoderm
      differentiation and beta 1 tubulin expression in the apodemes during embryonic
      development. The beta 3 tubulin isotype is first detectable at the extended
      germband stage shortly before the separation of somatic and visceral derivatives.
      Comparing the distribution of the beta 3 mRNA and the beta 3 isotype shows that
      the transcription of the beta 3 tubulin gene is cell type specifically repressed
      during differentiation of individual mesodermal derivatives, from which the
      dorsal vessel remains transcriptionally active until shortly before hatching. In
      contrast the beta 3 tubulin protein is detectable in all mesodermal derivatives.
      The beta 3 tubulin is an excellent marker to study mesoderm differentiation on a
      regulatory and cellular level using both genetics and molecular biology. In the
      visceral mesoderm, the expression of the beta 3 tubulin gene is regulated by
      homeotic gene products, while other transactivators regulate expression in the
      dorsal vessel and the body wall musculature. In the somatic mesoderm, the beta 3
      tubulin allows to visualize myotube formation and insertion into the epidermis.
      This contact to the epidermal attachment sites (apodemes) induces beta 1 tubulin
      expression, as can be seen in double staining experiments. We determined a 14bp
      cis-regulatory enhancer element guiding expression of the beta 1 tubulin gene in
      these attachment sites. Using the beta 1 and beta 3 tubulin isotypes as markers
      we started to isolate mutants which are disturbed in muscle formation.

PMID- 8735929
TI  - Larval and imaginal pathways in early development of Drosophila.
AB  - In holometabolous development, higher insects have two different life forms, the
      larva and the imago. Both larval and imaginal cells are derived from cells of the
      blastoderm stage. After the final embryonic wave of mitosis, however, only the
      imaginal cells remain diploid, proliferate massively and do not differentiate
      until metamorphosis. The separation of these two pathways was described by many
      authors as a fundamental process that must take place at a very early stage of
      development, most probably the blastoderm stage. Mainly by using single cell
      transplantations at the blastoderm or early gastrula stages, respectively, we
      found common cell lineages between larval and imaginal structures by clones
      overlapping in the ectoderm (i.e. larval epidermal cells and imaginal discs
      within a segment, or larval and imaginal salivary gland cells), the mesoderm
      (i.e. larval somatic muscles and adepithelial cells), and the endoderm (i.e.
      larval and imaginal midgut cells). From these findings we conclude that it seems
      to be a principle in Drosophila embryogenesis that the separation of larval and
      imaginal pathways is postponed to a later developmental stage.

PMID- 8735930
TI  - Allatotropin released by the brain controls larval molting in Galleria mellonella
      by affecting juvenile hormone synthesis.
AB  - Monoclonal antibodies were raised against a protein fraction which was purified
      from larval brains of Galleria mellonella and which was shown to stimulate the
      corpora allata to synthesize juvenile hormone in vivo as well as in vitro.
      Immunoblot analysis revealed that one polypeptide band of 20 kDa was specifically
      recognized. Two pairs of median neurosecretory cells of the brain and the cells
      of the corpus cardiacum were demonstrated to be immunoreactive to the antibodies.
      Our results sustain the hypothesis that the larval brain directly governs insect
      larval molting by controlling JH synthesis via an allatrophic factor.

PMID- 8735931
TI  - Cell lineage and cell fate in crustacean embryos--a comparative approach.
AB  - Malacostracan crustaceans undergo a complex and stereotyped cleavage pattern
      during formation of and segmentation in their post-naupliar germ band. This
      pattern has been studied in several malacostracan representatives with respect to
      morphogenesis and expression of the engrailed gene. Although this cell lineage
      pattern is specific and invariant in each species, comparative analyses reveal
      subtle differences between different parts of individual germ bands and between
      germ bands of different species. We conclude that despite the elaborate cleavage
      pattern, cell fate specification is not closely linked to cell lineage.
      Furthermore, some aspects of the evolutionary alterations of germ band formation
      and segmentation in annelids and arthropods are discussed.

PMID- 8735932
TI  - Large scale genetics in a small vertebrate, the zebrafish.
AB  - The systematic isolation and characterization of mutants in Drosophila has
      enormously facilitated the analysis of molecular mechanisms underlying
      developmental pathways in the embryo. A similar approach is presently being used
      to study embryonic development of the zebrafish, which is becoming a mainstream
      model organism for vertebrate development. With its genetic versatility and
      sophisticated embryology, zebrafish offers the possibility to rapidly increase
      our knowledge of vertebrate development and add to what we have learned from
      other vertebrate model organisms.

PMID- 8735933
TI  - Neural crest cell migration and pigment pattern formation in urodele amphibians.
AB  - This review deals with research on the development and differentiation of the
      neural crest (NC) in amphibians carried out during the past twenty years. First,
      earlier studies on the migration and differentiation of NC cells in vitro are
      summarized. These studies include the modes of NC cell migration and their
      differentiation into chondroblasts, perichondral cells, neurons, Schwann cells
      and pigment cells (melanophores and xanthophores). Then a summary is given on the
      development of cranial sensory ganglia and enteric ganglia in Xenopus laevis. In
      the subsequent sections, mechanisms of NC cell migration are investigated in
      Ambystoma mexicanum, the Mexican axolotl (wild-type and white mutant) using
      ultrastructural, immunohistochemical and biochemical methods. In wild-type or
      dark axolotl embryos, pigment cells leave the NC and migrate out under the
      epidermis, whereas in the white mutant, pigment cells remain closely confined to
      the original position of the NC. This system provides an excellent model for
      analyzing NC cell migration in vertebrate embryos. Further sections deal with the
      development of larval pigment patterns in Triturus alpestris, (horizontal
      melanophore stripes) and Ambystoma mexicanum (vertical melanophore bars).
      Comparing the formation of these patterns shows that two different principles
      exist in the distribution of pigment derivatives of the NC: patterns following
      environmental cues (Triturus) and those ignoring these cues, relying solely on
      cell-cell interactions (Ambystoma). Other studies relate to evolutionary
      perspectives in pigment pattern formation. They are based on phylogenetic
      analyses of North American ambystomatids, combined with data on pigment patterns
      and their formation where such data are available. These studies have shown that
      vertical bars which develop from aggregates in the NC string are an evolutionary
      innovation, compared to the more primitive horizontal stripes lacking aggregates
      in the NC. Thus, in this review we show that the NC of amphibians (T. alpestris,
      Xenopus laevis, dark and white axolotls and other ambystomatids) may be used for
      various analyses concerning the migration and differentiation of its derivatives,
      as well as for studies on the formation and evolution of pigment patterns.

PMID- 8735934
TI  - Localization of a high molecular weight form of DNA topoisomerase I in amphibian
      oocytes.
AB  - Xenopus oocytes express a 165 kDa variant of DNA topoisomerase I (topo I) as
      opposed to the canonical 110 kDa form of somatic cells (Richard and Bogenhagen,
      Dev. Biol. 146: 4-11, 1991). By immunofluorescence microscopy using variant
      specific antibodies we show that this high molecular weight form is associated
      with lampbrush chromosome loops and the inner regions of the amplified nucleoli.
      Inhibition of topo I-activity by either Camptothecin-treatment or microinjection
      of neutralizing antibodies resulted in loop retraction and the condensation of
      chromosomes and amplified nucleoli. These data indicate that the oocyte-specific
      165 kDa form of topo I is involved in transcriptional processes mediated by RNA
      polymerase I and II and is therefore functionally equivalent to the somatic cell
      110 kDa counterpart.

PMID- 8735935
TI  - A fork head related multigene family is transcribed in Xenopus laevis embryos.
AB  - We have isolated and sequenced ten different members of the fork head/HNF-3
      multigene family from Xenopus laevis which have been termed Xenopus fork head
      domain related (XFD) genes 1 to 10. Another four isolated genes (XFD' genes)
      represent pseudo-allelic variants which arose by an ancient tetraploidization
      within this species. Whereas all genes of this multigene family exhibit a high
      degree of sequence homology within the evolutionary conserved fork head domain,
      sequences outside this module are substantially different. Based upon sequence
      homologies over the entire coding sequences, XFD-7/7' represent the Xenopus
      homologs to the rodent hepatocyte nuclear factor HNF-3 alpha, while XFD-3/3'
      encode the homologs to HNF-3 beta. Here we present an analysis of the temporal
      transcription pattern of XFD genes 1 to 10 during embryogenesis and in some adult
      tissues. Eight of these XFD genes are activated during embryonic development, but
      show different and distinct transcription profiles. The localization of
      transcripts was determined by whole-mount in situ hybridization. Although
      transcription of individual XFD genes partially overlaps, each gene is
      characterized by means of a specific spatial pattern of transcriptional activity.

PMID- 8735936
TI  - Retinoic acid receptors and nuclear orphan receptors in the development of
      Xenopus laevis.
AB  - Nuclear hormone receptors are ligand-activated transcription factors that
      regulate the expression of target genes by binding to hormone responsive elements
      (HRE) in their 5' upstream region. Retinoids which are known for their
      teratogenicity and which have a potential role in the specification of the
      anteroposterior axis of vertebrate embryos regulate transcription via a hormone
      like mechanism by activating nuclear retinoic acid receptors, designated RAR and
      RXR. Of the several isoforms of RAR found in embryos of Xenopus laevis, xRAR
      gamma 2 appears to be the most abundant. During the early retinoic acid-sensitive
      period of development, the total amount of xRAR gamma 2 transcript and protein is
      increased and a highly specific pattern of expression emerges. During
      neurulation, the receptor is predominantly found in the dorsal posterior region,
      in the head endomesoderm, and in the rostral hindbrain. The dependence of this
      pattern on mesoderm induction and on neural induction is discussed. Contrasting
      with the elaborate pattern of xRAR gamma 2, the FTZ-F1-related nuclear orphan
      receptors (xFF1rA/B) are ubiquitous nuclear proteins in Xenopus embryos, as are
      the peroxisome proliferator-activated receptors xPPAR alpha and beta. PPARs are
      activated by polyunsaturated fatty acids and regulate the synthesis of enzymes
      involved in lipid metabolism. Later in development, the isoforms xPPAR alpha,
      beta, and gamma attain different tissue specificities.

PMID- 8735937
TI  - Spatial arrangement of intra-nucleolar rDNA chromatin in amplified Xenopus oocyte
      nucleoli: structural changes precede the onset of rDNA transcription.
AB  - Amphibian oocyte nucleoli are a particular suited object for research on
      nucleolar chromatin organization. By selective rDNA amplification each pachytene
      oocyte nucleus accumulates 30 pg of extrachromosomal rDNA, this amount
      corresponds to 2 million rDNA copies. Following the selective amplification
      stage, the amplified gene copies are finally distributed within more than
      thousand extrachromosomal nucleoli per individual oocyte nucleus. The aim of the
      present study was first to obtain a precise documentation of the fate of
      amplified rDNA during early Xenopus oogenesis until the final functional
      integration of these copies into individual oocyte nucleoli, and, second, a close
      correlation of the structural data with determination of rDNA transcription rates
      by S1 transcript analysis for the subsequent stages of oocyte differentiation. In
      order to investigate the structural complexity of the intranuclear rDNA
      translocation process in detail, a confocal laser scan microscope (CLSM) was
      used, equipped with an external UV-laser. This instrumentation unambiguously
      allowed (i) the detection of small clusters of rDNA copies and (ii) the precise
      spatial documentation of the intranuclear position of rDNA clusters in relation
      to the protein-free pre-nucleolar protein bodies, a specific characteristic of
      late pachytene/early diplotene amphibian oocyte nuclei. Our results indicate that
      the major rDNA translocation processes, e.g. the association of rDNA clusters
      with pre-nucleolar protein bodies, the formation of ribbon-like pre-nucleolar
      units sensu Van Gansen and Schramm (J. Cell Sci. 10: 339-367, 1972), and,
      finally, the translocation of fused rDNA units into the interior of pre-nucleolar
      protein bodies, occur--for the most part--in absence of massive rDNA
      transcription. As shown by the S1 transcript analysis, the onset of massive rDNA
      transcription starts concomitantly with an unraveling of the densely packed rDNA
      clusters into finely dispersed rDNA units, which were shown by CLSM analysis to
      be distributed throughout the entire nucleolar volume.

PMID- 8735938
TI  - Nucleoskeleton and nucleo-cytoplasmic transport in oocytes and early development
      of Xenopus laevis.
AB  - We use amphibian oocytes and eggs as favorite biological systems to study various
      cell biological phenomena. We have analyzed the role of the zinc finger protein
      TFIIIA and ribosomal protein L5 in nucleo-cytoplasmic transfer of 5S ribosomal
      RNA and report on the structural requirements of the 5S RNA for the interaction
      with TFIIIA. Furthermore, we have used the oocyte/egg system to analyze the
      kinetics of the posttranslational isoprenylation of oocyte nuclear lamin B3 and
      its fate during egg maturation. We demonstrate, that isoprenylation of newly
      synthesized lamins takes place in the oocyte cytoplasm before uptake into the
      nucleus and show, that the isoprene modifications alone are not sufficient to
      maintain stable association of lamins with nuclear envelope derived membranes in
      eggs. Finally, initial results of the identification of cis-acting sequence
      elements, involved in translational repression of lamin mRNAs in oocytes, are
      reported.

PMID- 8735940
TI  - Zinc finger proteins in early Xenopus development.
AB  - The C2H2-type zinc finger motif defines a large super family of specific DNA and
      specific RNA binding proteins. Individual members of this protein family have
      been demonstrated to carry important regulatory functions in embryogenesis. We
      have isolated a large collection of C2H2-type zinc finger proteins from Xenopus
      laevis. Some of these proteins are highly conserved in evolution and found to be
      differentially expressed during embryonic development of the central nervous
      system. We also summarize our recent findings on the biochemical characterization
      of RNA and DNA binding activities in vitro for other Xenopus zinc finger
      proteins, which fall into structurally defined, distinct subfamilies.

PMID- 8735939
TI  - Factors responsible for the establishment of the body plan in the amphibian
      embryo.
AB  - A central topic of embryology is the establishment of the body plan during
      embryogenesis. Starting with maternal factors distributed in the early cleavage
      stages in distinct patterns and gradients cell-to-cell interactions including
      early embryonic induction result in the formation of mesoderm and the organizer
      area. While many facts are known about the role of growth factors like activin
      (closely related to the vegetalizing factor), processed Vg1, BMPs and FGF for
      mesoderm formation, the establishment of the central nervous system is not yet
      well understood. However, there is growing evidence that neural induction is a
      multistep process at the level of the dorsal mesoderm (organizer) and the
      reacting neuroectoderm. Therefore the existence of only one neuralizing factor is
      unlikely. We report about data that follistatin protein is not a direct neural
      inducer. Furthermore our comparative studies of Xenopus and Triturus exogastrulae
      indicate that planar signals are unlikely in the Triturus embryo (urodeles)
      during the early steps of neural induction. Vertical signals emanating from the
      chordamesoderm are essential for the terminal neuralization and regionalization
      of the central nervous system during gastrulation for both Xenopus and Triturus.
      The putative role of neuralizing factors and BMP/activin-like molecules for the
      stabilization or shift of neuroectoderm into different pathways of
      differentiation (epidermis or neural default state) is discussed.

PMID- 8735941
TI  - Regulation and function of the tissue-specific transcription factor HNF1 alpha
      (LFB1) during Xenopus development.
AB  - We review the data available on the structure, developmental appearance and
      embryonic regulation of the tissue-specific transcription factor HNF1 alpha
      (LFB1) in Xenopus. The expression of the HNF1 alpha gene starts early in
      embryogenesis shortly after mid-blastula transition and the protein accumulates
      in the region of the embryo where liver, pronephros and gut--tissues that contain
      HNF1 alpha in the adult--are developing. The cofactor DCoH, known to stabilize
      dimer formation of HNF1 alpha, is present as a maternal factor in the egg and has
      a partially distinct tissue distribution compared to HNF1 alpha. This implies
      that DCoH does not only modulate HNF1 alpha dimerization but may also cooperate
      with other transcription factors. By injecting HNF1 alpha promoter CAT constructs
      into fertilized Xenopus eggs we obtained activation of the injected gene
      restricted to the region of the developing larvae expressing endogenous HNF1
      alpha. Deletion analysis allowed to define the OZ-element that is essential for
      embryonic activation. This element also occurs in other promoters activated at
      mid-blastula transition in the embryo and interacts with the maternal factor OZ
      1. As the HNF1 alpha promoter also contains functional binding sites for HNF4 and
      HNF1, we postulate that all of these transcription factors contribute to the
      cascade leading to proper embryonic activation of the HNF1 alpha gene.

PMID- 8735942
TI  - Mesoderm migration in the Xenopus gastrula.
AB  - During Xenopus gastrulation, the mesoderm involutes at the blastopore lip and
      moves on the inner surface of the BCR toward the animal pole of the embryo.
      Active cell migration is involved in this mesoderm translocation. In vitro,
      mesoderm cells migrate non-persistently and intermittently by extending and
      retracting multiple lamellipodia, which pull the cell body in their direction.
      Lamellipodia formation is induced by FN. FN fibrils are present on the BCR as
      part of the in vivo substrate of mesoderm migration. Mesoderm cells can attach to
      the BCR independently of FN, but interaction with FN is required for lamellipodia
      extension and cell migration on the BCR. In contrast to preinvolution mesoderm,
      involuted migrating mesoderm always stays on the surface of the BCR cell layer:
      migrating mesoderm cells do not mix with BCR cells, and a stable interface
      between tissues is maintained. A corresponding change in cell sorting behavior
      occurs during mesoderm involution. In Xenopus, the mesoderm moves as a
      multilayered coherent cell mass held together by cadherin-mediated cell adhesion.
      Aggregate formation changes mesoderm cell behavior, rendering it more continuous,
      persistent and directional, i.e. more efficient. The mesoderm possesses an
      intrinsic tissue polarity which biases the direction of its movement. In
      addition, the fibrillar FN matrix of the BCR contains guidance cues which also
      direct the mesoderm toward the animal pole. Haptotaxis is most likely not
      involved in this substrate-dependent guidance of the mesoderm, but intact FN
      fibrils seem to be required. A polarity of the BCR cell layer which underlies
      this anisotropy of the BCR matrix develops under the influence of the marginal
      zone in the late blastula. Although in other amphibian species, gastrulation
      depends critically on mesoderm cell migration, in Xenopus, convergent extension
      of the axial mesoderm seems to provide the main driving force for gastrulation.

PMID- 8735943
TI  - Metamorphosis and pattern formation in Hydractinia echinata, a colonial hydroid.
AB  - There are several reasons why Hydractinia echinata Hydrozoa, Cnidaria) is
      excellently suited to study developmental processes. In the laboratory
      fertilization takes place every morning in the seawater in thousands of eggs.
      Cleavage starting synchronously leads to a ciliated planula larva within 2 to 3
      days. Onset of metamorphosis from the larval to the polyp stage must be triggered
      externally. There are several agents known to induce or to interfere with
      induction of metamorphosis thus allowing access to the biochemical basis of this
      process. The pattern of the resultant polyp can be influenced by certain
      treatments during the process of metamorphosis allowing access to a process of
      proportioning. The colony develops by elongation of hollow tubes at the base of
      the polyps, termed stolons on which in more or less regular intervals new polyps
      emerge. Two (main) types of polyps are formed allowing to study spacing by
      lateral inhibition and lateral dependence of each other. In the present paper
      current data and hypotheses concerning all these topics are discussed.

PMID- 8735944
TI  - Signals and signal-transduction systems in the control of development in Hydra
      and Hydractinia.
AB  - Pattern control in Hydra has traditionally been assigned to the determining
      influence of morphogens and neuropeptides. However, at present, arachidonic acid
      and its derivative 12-S-HETE are the only identified, potential signal molecules
      known to promote head and bud formation. More potent factors might exist but are
      not yet identified. Nonetheless, it is possible to evoke the development of an
      almost unlimited number of supernumerary head structures and to induce ectopic
      foot formation by interference with the PI-PKC signal transducing system. Such an
      interference can also rescue the regeneration-deficient mutant reg-16. Regarding
      signals in the development of Hydractinia, metamorphosis is induced by an
      external key stimulus, i.e. a lipid derived from environmental bacteria. The
      reception of this stimulus involves PKC-mediated responses. Upon its reception, a
      neuropeptide is released as an internal, synchronising signal. Members of the
      novel LWamide family of peptides appear to represent this internal signal. In
      postmetamorphic development, a glycoprotein SIF serves as an inducer of stolon
      formation.

PMID- 8735945
TI  - Checkpoints in the life-cycle of Cassiopea spp.: control of metagenesis and
      metamorphosis in a tropical jellyfish.
AB  - Experimental data reveal that most, if not all, major events in the metagenetic
      life-cycle of Cassiopea spp. at these checkpoints depend on the interaction with
      specific biotic and physical cues. For medusa formation within a permissive
      temperature range by monodisk strobilation of the polyp, the presence of
      endosymbiotic dinoflagellates is indispensable. The priming effect of the algal
      symbionts is not primarily coupled with photosynthetic activity, but was found to
      be enhanced in the light. Budding of larva-like propagules by the polyp, however,
      is independent from such zooxanthellae. On the other hand the budding rate is
      influenced by various rearing conditions. Exogenous chemical cues control
      settlement and metamorphosis into scyphopolyps of both sexually produced planula
      larvae and asexual propagules. In laboratory experiments two classes of
      metamorphosis inducing compounds have been detected: a family of oligopeptides,
      featuring a proline-residue next to the carboxyterminal amino acid, and several
      phorbol esters. Using the peptide 14C-DNS-GPGGPA, induction of metamorphosis has
      been shown to be receptor-mediated. Furthermore, activation of protein kinase C,
      a key enzyme within the inositolphospholipid-signalling pathway appears to be
      involved in initiating metamorphosis. In mangrove habitats of Cassiopea spp.
      planula larvae specifically settle and metamorphose on submerged, deteriorating
      mangrove leaves from which biologically active fractions have been isolated. The
      chemical characterisation and comparison of these compounds from the natural
      environment with the properties and mode of action of oligopeptide inducers is in
      progress.

PMID- 8735946
TI  - Neuronal control of development in hydra.
AB  - Hydra is an excellent model system for developmental biology, because pattern
      formation processes can be easily studied in regeneration, transplantation, and
      reaggregation experiments. At the cellular level hydra has the advantage that it
      contains only a few basic cell types and that differentiation pathways are short.
      Two types of signals, produced and released by nerve cells, control the spatial
      and temporal patterns of differentiation. Positive signals induce specific local
      differentiation events, and negative signals inhibit the spread of such
      inductions to larger areas. Head-specific growth and differentiation are
      controlled by head activator and head inhibitor, food-specific processes are
      regulated by foot activator and foot inhibitor. The activators are peptides, the
      inhibitors are low-molecular-weight substances. The sequence of the head
      activator is known, and it is conserved throughout the animal kingdom. At the
      cellular level head activator exerts three types of effects in hydra. It
      stimulates cells to divide, and it is responsible for the determination and the
      final differentiation of nerve cells and head-specific epithelial cells. For
      nerve-cell differentiation the cAMP pathway is used as second messenger system.
      Components of this pathway were identified in hydra. In mammals head activator is
      produced by nerve and neuro-endocrine cells, and it acts as mitogen on cells of
      neural origin. It is present early in neural development and in abnormal neural
      development, such as brain and neuroendocrine tumours.

PMID- 8735947
TI  - Targeted inactivation of myogenic factor genes reveals their role during mouse
      myogenesis: a review.
AB  - The role of the four myogenic regulating genes Myf-5, myogenin, MyoD, and MRF4
      (herculin, Myf-6) during mouse embryogenesis has been investigated by targeted
      gene inactivation. Null mutations for the MyoD gene generate no skeletal muscle
      phenotype due to a compensatory activation of the Myf-5 gene. Mice carrying a
      homozygous Myf-5 mutation exert considerably delayed myotome formation with
      unexpected consequences. While skeletal myogenesis in these mutant mice resumes
      normally at the onset of MyoD expression, a skeletal defect of the ribs persists.
      Apparently, Myf-5 and MyoD individually are not absolutely essential for skeletal
      muscle development, most likely because they have overlapping or redundant
      functions. In fact, double mutants lacking both, MyoD and Myf-5, fail to develop
      skeletal musculature and the muscle forming regions seem to be devoid of
      myoblasts. Homozygous inactivation of the myogenin gene leads to drastically
      reduced myofiber formation. These mice accumulate apparently normal numbers of
      myoblasts which are arrested in their terminal differentiation program. Myf-6
      null mutant mice exhibit drastically reduced expression of Myf-5 for reasons
      presently unknown. The phenotype is very similar to Myf-5 mutants with an
      additional reduction of deep back muscles and minor alterations in sarcomeric
      protein isoforms. Based on the phenotypes obtained from these various gene "knock
      out" mice, we now begin to understand the regulatory network and the homostatic
      relationship of genes which are critically involved in myogenesis of vertebrates.

PMID- 8735948
TI  - Malformations after radiation exposure of preimplantation stages.
AB  - Our studies have shown that, contrary to the opinion in most textbooks, it is
      possible to increase the number of malformed fetuses in one of our mouse strains
      (originally "Heiligenberger Stamm", meanwhile HLG/Zte) by radiation exposure of
      zygotes or of subsequent preimplantation stages. The malformation affected most
      pronouncedly is gastroschisis, a defect occurring at a frequency of 1 to 4% in
      the controls. The observed increase is strain specific (C57Bl mice or
      (HLGxC57Bl)F1 hybrids do not react in the same way), it is accompanied by an
      increased frequency of chromosomal aberrations in skin fibroblasts and of
      modified protein patterns in liver, kidney, and skin cells of day 19 fetuses. The
      most probable explanation seems to be the assumption that radiation exposure of
      preimplantation stages increases a defect with a genetic predisposition in a
      specific way and labelizes the genome of subsequent cell generations making these
      cells more susceptible for noxes acting on the fetus.

PMID- 8735949
TI  - Expression pattern of different gap junction connexins is related to embryo
      implantation.
AB  - Successful implantation in mammals requires a close interaction between the
      embryo and the uterus. Direct cell-cell communication via gap junctions seems to
      play an important role in the preparation of the uterus for embryo implantation
      and in the regulation of trophoblast invasion. During preimplantation in the rat
      the gap junctional proteins connexin (cx) 26 and cx43 are suppressed. This loss
      of cell-cell communication seems to be important for transformation of the
      endometrium into the receptive phase. The suppressive effect is mediated by
      progesterone as demonstrated by the application of antigestagens. At
      implantation, however, a spatial and temporal pattern of connexin expression is
      induced in response to embryo recognition. cx26 is locally expressed in the
      uterine epithelium of the implantation chamber, cx43 in the surrounding decidua
      prior to invasion. With progressing invasion, the decidual cells surrounding the
      invading trophoblast in addition to cx43 reveal cx26. In this phase, the invasive
      partner, the blastocyst, is characterized by coexpression of cx43 and cx31.
      During trophoblast invasion however, cx31 becomes restricted to the cells of the
      invasive ectoplacental cone, cx43 to the embryo proper. It seems that
      compartmentalization of the trophoblast and the inner cell mass is established by
      two different connexins. During placental differentiation connexin expression
      switches from cx31 to cx26 and cx43, indicating the end of the invasive phase.
      The highly regulated pattern of connexin expression in the endometrium as well as
      in the trophoblast suggests a key role of this different intercellular pathways
      in regulating the invasion process of the trophoblast into its host tissue, the
      endometrium.

PMID- 8735950
TI  - Pax and vertebrate development.
AB  - Pax genes encode transcription factors sharing a highly conserved sequence, the
      paired box. Their temporally and spatially restricted expression patterns during
      development indicate that Pax genes are involved in important steps of nervous
      system formation. Mutations in Pax genes have been correlated with three mouse
      mutants (undulated, splotch, small eye) and two human diseases (Waardenburg
      syndrome, aniridia). Recent data demonstrated that deregulation of Pax genes
      contributes to tumor formation.

PMID- 8735951
TI  - Stage and developmental specific gene expression during mammalian
      spermatogenesis.
AB  - Spermatogenesis is a complex developmental process which involves amplification
      of germinal stem cells, their differentiation into spermatocytes, meiotic
      division and finally transformation into mature spermatozoa. Therefore,
      spermatogenesis provides an interesting system for examining the regulation of
      gene expression during development and differentiation. The genes expressed
      during spermatogenesis can be divided into two main groups: diploid and haploid
      expressed genes. In this review, we report about the regulation of expression of
      a diploid expressed gene, namely the proacrosin gene, and that of a haploid
      expressed gene, the transition protein 2 gene.

PMID- 8735953
TI  - Epithelial cell polarity and embryo implantation in mammals.
AB  - At embryo implantation we are confronted with the fact that uterine and
      trophoblast epithelium make contact via their apical cell membranes. This
      epithelium-epithelium adhesion leading to definitive attachment of the embryo to
      the uterine wall, however, is far from being trivial and has been called a cell
      biological paradox. It has been proposed that some of the molecular events
      involved in epithelium-to-mesenchyme transformation might play a role in the
      interaction between uterine cells and trophoblast. As a mechanism to achieve
      uterine epithelium adhesiveness for trophoblast it is postulated that uterine
      cells partially modulate their epithelial phenotype. Data from recent in vitro
      experiments give support to this hypothesis and suggest that loss of apical-basal
      cell polarity might prepare the apical cell pole of uterine epithelium for cell
      to-cell contact with trophoblast in vivo.

PMID- 8735954
TI  - Organization and expression of the developmentally regulated H1(o) histone gene
      in vertebrates.
AB  - The H1 class of histones comprises several main-type, S-phase dependent isoforms
      and, in addition, a sperm-specific H1t and a peculiar subtype, H1 zero, which is
      confined to highly differentiated cells. In contrast to main type histone genes,
      the H1 zero gene expression does not strictly depend on DNA replication. Also in
      contrast to the other H1 subtype genes, the mammalian H1 zero gene is not
      included in a histone gene cluster and its mRNA differs in structure, size and
      mode of processing from other histone mRNAs. The regulation of expression of the
      H1 zero gene varies from main type H1 genes in several respects. This is
      manifested in the promoter structure which contains sequence elements that are
      also found in main type H1 promoters, but also shows regulatory motifs which
      appear to be involved in a developmental regulation of the H1 zero gene, such as
      a retinoic acid receptor binding site, which has been described in the mammalian
      H1 zero gene promoter.

PMID- 8735952
TI  - Stage-specific gene expression during rat spermatogenesis: application of the
      mRNA differential display method.
AB  - Spermatogenesis is a complex differentiation process which requires the
      coordinate synthesis of diverse stage-specific proteins. In attempting a large
      scale identification and characterization of those proteins, we have made use of
      the recently described mRNA differential display method (Liang and Pardee,
      Science 257: 967-971, 1992). This method is based on the reverse transcription of
      mRNAs obtained from two different cell populations (pachytene spermatocytes and
      spermatids in the present study) followed by a PCR reaction and comparison of the
      individual cDNA populations in a polyacrylamide gel system. Up to the present we
      have been able to identify 268 cDNA bands. Most of them (77%) are common to both
      cell stages. From the differentially expressed bands (23%) an ample majority was
      spermatid-specific (74%). According to our present results we conclude that the
      mRNA differential display is a promising approach for investigations on stage
      specific gene expression during a differentiation process like spermatogenesis.

PMID- 8735955
TI  - Fibroblast growth factor and its implications for developing and regenerating
      neurons.
AB  - FGF is a multifunctional heparin-binding protein which was characterized by its
      mitogenic and angiogenic action outside the nervous system. Recent data confirm
      this multifunctionality also with regard to the nervous system. The distribution
      of FGF and its receptors seems not to be in agreement with the idea of a single
      function for one population but argues for a more complex action, which might be
      dependent on the development stage and cell type. FGF and its receptors are
      widely distributed in the nervous system. In brainstem and spinal cord
      motoneurons and in sensory ganglia the FGF-2 staining pattern is developmentally
      regulated suggesting a functional change during embryonic and postnatal
      development. In addition, after nerve lesion the FGF-2 expression is altered in
      sensory and motoneurons. Administration of FGF-2 reveals trophic effects on
      survival and transmitter metabolism in vivo and in vitro. According to a more
      general neurotrophic factor concept, a physiological role of FGF for distinct
      neuron populations during development is likely. In the motor system, for
      example, FGF could act synergistically with certain neurotrophins, CNTF, or other
      non-identified co-factors. In the sensory system, a possible non-neurotrophic
      role for at least postnatal and adult sensory neurons has to be further addressed
      in the future. In order to further define and characterize the actions of the
      FGFs a mapping of the different family members and their respective receptor
      molecules during development and in the adult has to be done.

PMID- 8735956
TI  - The formation of somite compartments in the avian embryo.
AB  - The somites develop from the unsegmented paraxial mesoderm that flanks the neural
      tube. They form in an intrinsic process which lays down the primary segmental
      pattern of the vertebrate body. We review the processes of somitogenesis and
      somite differentiation as well as the mechanisms involved in these developmental
      events. Long before overt differentiation occurs, different compartments of the
      still epithelial somites give rise to special cell lines and to particular
      derivatives. By means of isotypic grafting between quail and chick embryos, it is
      possible to follow the fate of groups of somitic cells. In this way, the
      development of the myotome and the back dermis from the dorsomedial quadrant and
      of the hypaxial body wall and limb musculature from the dorsolateral quadrant was
      established. The two ventral quadrants and the somitocoele give rise to the
      chondrogenic/fibroblastic lineage of the sclerotome and form the vertebral
      column. Somite compartments can first be visualized by the expression pattern of
      Pax genes. Pax-3 is expressed in the dorsal part of the epithelial somite, while
      the ventral two thirds express Pax-1, a marker of sclerotome development. Pax-3
      expression is retained also in the premitotic myogenic cells that migrate into
      the limb buds. In differentiating myoblasts, Pax-3 expression is turned down and
      taken over by the activation of MDF's. This initial event in myogenesis occurs in
      the absence of local signals, whereas the expression of Pax-1 in the sclerotome
      can be shown to be induced by signals from the notochord and floor-plate of the
      neural tube. Epaxial myotome differentiation is supported by the neural tube,
      after the neural tube has received patterning signals from the notochord. The
      hypaxial musculature and limb musculature differentiate independently of the
      axial structures. The myogenic cells migrating within the limb buds respond to
      signals of the lateral plate mesoderm which guide their distalward migration and
      pattern the muscle.

PMID- 8735958
TI  - The use of fluorescent marker dyes for studying intercellular communication in
      nematode embryos.
AB  - As more and more cases of necessary cell-cell interactions are revealed, the
      classical view of mosaic development in nematodes has to be replaced by a more
      dynamic picture showing different types of intercellular communication. To
      investigate the pattern and function of communication pathways between cells, we
      have developed different techniques to shunt fluorescent marker dyes into embryos
      and hatched animals and study their distribution in vivo. During embryogenesis we
      find that for a long time all somatic cells form a single dye-coupling
      compartment while transfer into the germline is restricted already at an early
      stage. Considerable variations between species with respect to the size of
      communication channels and the time during which these are functional are
      observed and can be correlated to differences in the developmental program. A
      different kind of intracellular communication can be visualized with the help of
      fluorescent dyes: a transfer of yolk proteins in two phases of the life cycle, in
      the adult hermaphrodite from the gut into the maturing germ cells, and in the
      embryo from non-gut cells into the gut primordium. Cell-cell interactions in the
      nematode embryo can be inhibited with polysulfated hydrocarbon dyes (e.g. Trypan
      Blue) which bind strongly to the plasma membrane. In summary our data indicate
      that fluorescent marker dyes can be helpful tools to identify and understand the
      role of intercellular communication and transfer processes in nematode
      development.

PMID- 8735957
TI  - Metabolism of oocyte construction and the generation of histospecificity in the
      cleaving egg. Lessons from nereid annelids.
AB  - The growing oocyte and the developing egg of nereid polychaetes are easily
      accessible to observation and experimental work, a precondition for our research.
      In preparation for a single semelparous act of reproduction, nereid females
      reutilize somatic biomass for the synchronized production of numerous oocytes. To
      keep oogenesis going somatic resources become recycled by the eleocytes and are
      supplied to the oocytes in form of vitellogenin and nucleotides (among other
      identified and yet unidentified substances). Both oocytes and eleocytes are free
      floating coelomic cells. We postulate that availability of metabolites produced
      by the eleocytes might suffice to drive synchronous oocyte growth. The cortex of
      the fully differentiated oocyte contains numerous cortical granules which after
      fertilization empty by exocytosis thus causing a profound structural
      reorganization of the zygote cortex. Early development of nereids is extremely
      constant in time and spatial pattern and from the onset cleavages create
      diversity among the blastomeres. We have documented a correlation between the
      quality and amount of cytoplasm, the cell cycle duration and the histogenetic
      fate of such blastomeres. Experimental change of cytoplasmic proportions of early
      cleavage cells has serious consequences for axial development. Using a number of
      differentiation markers we were able to analyze the necessity of certain cleavage
      steps for the acquisition of the determined state.

PMID- 8735959
TI  - Differences in the neuropeptide Y-like immunoreactivity of the plasma and
      platelets of human volunteers and depressed patients.
AB  - In this study, patients with recurrent major depression were found to have
      significantly lower neuropeptide Y-like immunoreactivity (NPY-LI) in platelet
      poor plasma (p < 0.01) and significantly higher NPY-LI in platelets (p < 0.001)
      compared to controls. Also, qualitative differences in the NPY-LI in platelet
      poor plasma (PPP) and platelets were detected when the samples were analyzed by
      HPLC followed by RIA of the collected fractions.

PMID- 8735960
TI  - Release of serotonin from RBL-2H3 cells by the Escherichia coli peptide toxin
      STb.
AB  - Heat-stable enterotoxin b (STb) of Escherichia coli is a 48-amino acid basic,
      disulfide-bonded peptide that causes intestinal secretion in experimental animal
      models. Recent evidence suggests that the in vivo mechanism of STb action
      involves release of 5-hydroxytryptamine (5-HT) and production of prostaglandin E2
      (PGE2). Here we show STb-mediated release of 5-HT from rat basophilic leukemic
      cells (RBL-2H3), a mast cell line model used extensively to study 5-HT release.
      Increasing concentrations of biologically active STb resulted in a dose-dependent
      release of 5-HT from RBL-2H3 cells. In contrast to these results, reduced and
      alkylated STb had no effect on 5-HT release. Release of 5-HT from RBL-2H3 cells
      was independent of extracellular calcium ions and did not involve changes in the
      intracellular concentration of free Ca2+. In addition, pertussis toxin treatment
      completely blocked 5-HT release, indicating a role for a pertussis toxin
      sensitive G-protein in the mechanism of 5-HT release from this cell type.

PMID- 8735961
TI  - Complete primary structure of the molt-inhibiting hormone (MIH) of the Mexican
      crayfish Procambarus bouvieri (Ortmann).
AB  - The amino acid sequence of MIH was elucidated by means of digestions with
      specific proteases, manual Edman degradation, and mass spectrometry. MIH consists
      of a 72-residue peptide chain (molecular mass 8322 Da) with six cysteines forming
      three disulfide bridges that connect residues 7-43, 23-39, and 26-52. It has
      blocked N- and C-termini and lacks tryptophan, histidine, and methionine. MIH
      shows striking similarity to the crustacean hyperglycemic hormone (CHH) isomorphs
      of Procambarus bouvieri (90% identity) and to the MIH from Homarus americanus
      (79% identity) and Penaeus vannamei (46% identity). It is also related to the MIH
      from Carcinus maenas (28% identity) and Callinectes sapidus (28% identity).

PMID- 8735962
TI  - Influence of methylation or substitution of the histidine of HVFLRFamide on
      biological activity and binding of locust oviduct.
AB  - The FMRFamide-related peptide PDVDHVFLRFamide (SchistoFLRFamide) is involved in
      the neural control of locust oviducts, where it acts as a potent inhibitor of
      spontaneous and induced contractions. Previous studies have shown that the His
      residue in the truncated analogue HVFLRFamide is critical for the retention of
      inhibitory biological activity, whereas VFLRFamide, in which inhibitory
      biological activity is lost, is the minimum sequence for binding of comparable
      affinity to the parent compound. In the present study we have used binding and
      bioassay to further investigate the properties of the His residue in determining
      the inhibitory biological activity of HVFLRFamide. Substitution of His by the D
      isomer or Phe produced analogues with stimulatory rather than inhibitory
      activity, confirming the importance of the His moiety. In addition, inhibitory
      activity was retained when the His moiety was methylated at the N-3 position of
      the imidazole ring, but methylation of N-1 yielded a peptide that stimulated
      contractions. Inhibitory activity was further retained when Nn-methyl-L-His and
      D,L-1',2',4'-triazole-3-Ala were substituted for His. These results, along with
      binding studies, suggest that transfer of an imidazole proton is not responsible
      for inhibitory activity and further suggest that hydrogen bonding to the N-1 of
      the imidazole ring of histidine may be required to evoke the inhibitory response.

PMID- 8735963
TI  - Structure-activity relationships of KNEFIRFamide (AF1), a nematode FMRFamide
      related peptide, on Ascaris suum muscle.
AB  - Analogues of KNEFIRFamide (Lys-Asn-Glu-Phe-Ile-Arg-Phe-NH2; AF1), an FMRFamide
      related peptide (FaRP) originally isolated from Ascaris suum, were characterized
      in an A. suum muscle tension assay. AF1 had biphasic effects on this preparation,
      inducing a brief relaxation followed by excitation and spastic paralysis.
      Activity of AF1 in this assay was eliminated by N-terminal deletions and by
      deamidation of the carboxy-terminus. The potency of AF1 was greatly reduced by
      alanine substitution for any residue. Peptides that retained activity did not
      show the biphasic response observed with AF1, suggesting that the inhibitory and
      excitatory phases seen with AF1 may be due to activation of distinct receptors.
      The basis for the marked differences in potency observed between AF1 and the
      structurally related nematode FaRP, AF2 (KHEYLRFamide) was also tested. AF2 is
      approximately 1000-fold more potent than AF1 in this assay, but has physiological
      effects that are otherwise indistinguishable. KNEYIRFamide and KNEFLRFamide
      induced characteristic AF1/AF2 responses, but were much less potent than the
      native peptides. In contrast, KHEYIRFamide resembled AF1 in potency and pattern
      of responses. These data suggest that AF1 and AF2 act at distinct receptors, and
      hypothesis supported by the observation that KNEFIAFamide antagonized the effects
      of AF1 but not of AF2.

PMID- 8735965
TI  - Species differences in the localization of neuropeptide FF receptors in rodent
      and lagomorph brain and spinal cord.
AB  - Quantitative in vitro receptor autoradiography of [125I][D-Tyr1,(NMe)Phe3]NPFF
      was used to study the regional distribution of neuropeptide FF receptors in
      rodent and lagomorph brain. In rat, mouse, rabbit, and Afghan pika [125I][D
      Tyr1,(NMe)Phe3]NPFF binding sites were enriched in the superficial layers of
      dorsal horn of the spinal cord and in parabrachial nucleus, central gray matter,
      hypothalamus, and reunions thalamic nucleus. In other neuroanatomical regions,
      important species differences in NPFF receptor patterns are observed. In marked
      contrast, the brain and the spinal cord of the Octodon degus are devoid of NPFF
      receptors. The present study shows that in different species regional variations
      in brain NPFF receptor binding occur.

PMID- 8735964
TI  - Downregulation of mu-opioid binding sites following chronic administration of
      neuropeptide FF (NPFF) and morphine.
AB  - The effect of continuous ICV infusion of NPFF (10 micrograms/microliter) and
      morphine (40 micrograms/microliter) on mu-opioid binding sites was examined in
      rats using the in vitro radiolabeled techniques of whole-brain homogenate
      receptor binding and quantitative autoradiography. Mu receptors were labeled with
      [3H][D-Ala2-MePhe4,Glyol5] enkephalin in the homogenate binding experiments and
      with [125I][D-Ala2-MePhe4,Gly-ol5]enkephalin in autoradiographic studies. In
      homogenate binding studies, chronic administration of NPFF or morphine
      significantly downregulated mu receptors by 20% and 44%, respectively.
      Quantitative autoradiographic experiments demonstrated downregulation of mu
      opioid receptors in specific brain nuclei for both NPFF- and morphine-treated
      animals. Within the striatum and several nuclei of the thalamus, the mu receptors
      of the NPFF- and morphine-treated animals were decreased by 20-30% and 38-73%,
      respectively. These results suggest that NPFF may modulate opioid-mediated
      responses in part by altering the density of mu-opioid receptors.

PMID- 8735966
TI  - Kyotorphin synthetase activity in rat adrenal glands and spinal cord.
AB  - Kyotorphin, an endogenous [Met5]enkephalin-releasing antinociceptive dipeptide (L
      Tyr-L-Arg), is formed by kyotorphin synthetase from its constituent amino acids,
      L-Tyr and L-Arg, in the brain in an ATP-Mg(2+)-dependent manner. To elucidate the
      physiological role of kyotorphin in organs other than the brain, we examined the
      activity of kyotorphin synthetase in the rat adrenal glands and spinal cord. By
      Sephacryl S-300 gel-filtration chromatography of the soluble extracts from both
      the organs, the enzyme activity forming immunoreactive kyotorphin from L-Tyr and
      L-Arg in the presence of ATP and MgCl2 was detected in the fractions with the
      molecular mass of 200-300 kDa, being drastically reduced by the omission of ATP
      and MgCl2 from the reaction medium. The Km values of the partially purified
      adrenal and spinal kyotorphin synthetase for L-Tyr, L-Arg, ATP, and MgCl2 were
      close to those of the brain enzyme. The activity of adrenal kyotorphin synthetase
      was inhibited by some L-Arg analogues. NG-nitro-L-arginine methyl ester, alpha
      methyl-L-ornithine and D-Arg, but not by NG-nitro-L-arginine and N-iminoethyl-L
      ornithine. In the crude soluble extracts from the adrenal glands and spinal cord,
      kyotorphin was formed by kyotorphin synthetase, and also by the enzymatic
      processing of the precursor proteins, in the presence of physiological
      concentrations of L-Tyr and L-Arg in addition to ATP and MgCl2. Thus, kyotorphin
      synthetase resembling that in the brain is present in the rat adrenal glands and
      spinal cord. The present findings may predict a functional role of the L-Arg
      kyotorphin pathway in these organs.

PMID- 8735967
TI  - Kappa opioids exert a strong antiproliferative effect on PC12 rat
      pheochromocytoma cells.
AB  - Pheochromocytomas synthesize several types of opioids and their receptors.
      Opioids affect the proliferation rate of normal and tumoral cells. We have
      previously shown that the PC12 rat pheochromocytoma cells synthesize multiple
      opioids. The aim of the present work was to study the effect of opioids on the
      proliferation of these pheochromocytoma cells. Thus, the effect of several opioid
      agonists and antagonists was examined on basal and EGF-induced PC12 cell
      proliferation. The kappa opioid agonists dynorphin A, U-69593, and U-50488
      suppressed basal proliferation in a dose-dependent manner. The effect of kappa
      opioids was blocked by the general opioid antagonist naloxone and the selective
      kappa antagonist nor-binaltorphimine. Furthermore, both opioid antagonists given
      alone had a strong stimulatory effect, a findings suggesting that the
      proliferation of PC12 cells is under tonic inhibition by locally produced kappa
      opioids. Finally, the mu-opioid agonist DAGO and the delta and mu agonists DADLE
      and DSLET were ineffective.

PMID- 8735968
TI  - Mu-opioid receptor is involved in beta-endorphin-induced feeding in goldfish.
AB  - The present study evaluated the central effects of selective opioid receptor
      subtype agonists and antagonists on food intake in satiated goldfish. Significant
      increases in feeding behavior occurred in goldfish injected with beta-endorphin,
      the kappa agonist, U-50488, the delta agonist, [D-Pen2,D-Pen5]enkephalin (DPEN),
      and the mu agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO). On the other
      hand, the different receptor antagonists used: nor-binaltorphamine (nor-BNI) for
      kappa, 7-benzidilidenenaltrexone (BNTX) for delta 1, naltriben for delta 2, beta
      funaltrexamine (beta-FNA) for mu, and naloxonazine for mu 1, by themselves, did
      not modify ingestion or slightly reduced it. The feeding stimulation by beta
      endorphin was antagonized by beta-FNA and naloxonazine, but not by nor-BNI, BNTX,
      or naltriben. These data indicate that the mu-opioid receptor is involved in the
      modulation of the feeding behavior in goldfish.

PMID- 8735969
TI  - POMC-related products in the intermediate pituitary of the amphibian, Bufo
      marinus: differential subcellular processing in the Golgi and secretory granules.
AB  - In the intermediate pituitary of the anuran amphibian, Bufo marinus, the N
      acetylation of ACTH(1-13)-NH2 to yield alpha-MSH occurs as a cosecretory
      processing event, whereas the N-acetylation of beta-endorphin occurs as a
      posttranslational processing event. To understand how these two N-acetylation
      reactions are segregated, B. marinus intermediate pituitary cells were analyzed
      by immunogold labeling electron microscopy, and by using an ultracentrifugation
      procedure. The immunogold labeling studies indicated that ACTH(1-13)-NH2-related
      immunoreactivity was colocalized with N-acetylated beta-endorphin-related
      immunoreactivity in secretory granules. Furthermore, ACTH(1-13)-NH2-related
      immunoreactivity was not detected in either the ER or the Golgi. N-Acetylated
      beta-endorphin-related immunoreactivity, however, was detected in the Golgi.
      Ultracentrifugation analysis revealed that in an ER/microsomal fraction, beta-LPH
      sized and nonacetylated beta-endorphin-sized immunoreactive material were present
      in a molar ratio of 1:2. No N-acetylated forms of beta-endorphin were detected in
      the ER/microsomal fraction. In a Golgi/secretory granule fraction, the molar
      ratio of beta-LPH to beta-endorphin was 1:9 with 58% of the beta-endorphin being
      N-acetylated. Collectively, these data support the following hypotheses. The
      proteolytic cleavage of ACTH (1-39) to yield ACTH (1-13)-NH2 is a late processing
      event occurring in secretory granules. The cleavage of beta-LPH to yield
      nonacetylated beta-endorphin is an early processing event that may occur in the
      ER or the Golgi. Because N-acetylated beta-endorphin and nonacetylated ACTH(1-13)
      NH2 are colocalized in secretory granules, it appears, therefore, that the N
      acetylation of beta-endorphin is completed prior to loading into secretory
      granules. Thus, there is a spatial and temporal separation of the
      posttranslational processing events associated with the beta-LPH portion and ACTH
      portion of the POMC biosynthetic pathway in amphibian intermediate pituitary
      cells.

PMID- 8735970
TI  - Modulation of CRF-R1 mRNA in rat anterior pituitary by dexamethasone: correlation
      with POMC mRNA.
AB  - Glucocorticoids have been shown to decrease CRF receptor binding in the anterior
      pituitary. To determine whether glucocorticoids or CRF peptide modulate CRF-R1
      gene expression, CRF-R1 mRNA levels in rat pituitary and brain were measured
      after administration of a synthetic glucocorticoid, dexamethasone (DEX) or
      rat/human CRF (r/hCRF), using a sensitive solution hybridization RNase protection
      assay. DEX (400 micrograms/day) or r/hCRF (100 micrograms/kg/day) was
      administered twice daily for 5 days to male rats. DEX treatment caused a
      significant decrease in CRF-R1 mRNA levels in the anterior pituitary. Also, a
      significant positive correlation was found between CRF-R1 and POMC mRNA levels in
      the anterior pituitary of the individual animals: levels of both mRNAs were
      reduced by DEX. However, r/hCRF treatment had no significant effect on CRF-R1
      mRNA levels in the anterior pituitary. In extrahypothalamic brain regions, mRNA
      levels of CRF-R1 did not change following either DEX or r/hCRF administration.
      Our data suggest that in addition to POMC and CRF genes, CRF-R1 gene may also be
      subject to negative feedback control by glucocorticoids.

PMID- 8735971
TI  - Systemic nitroglycerin activates peptidergic and catecholaminergic pathways in
      rat brain.
AB  - In this study, we carried out an immunohistochemical evaluation of the
      neurochemical characteristics of neurons that are activated (i.e., express Fos
      protein) in response to systemic administration of nitroglycerin. In the brain
      stem, a significant percentage of activated neurons contained noradrenaline as a
      neurotransmitter, whereas only a few of them contained serotonin. In the
      paraventricular and supraoptic nuclei of the hypothalamus, numerous Fos
      immunoreactive neurons were also positive for vasopressin, oxytocin, and
      corticotropin-releasing factor. Codistribution with corticotropin-releasing
      factor was also observed in the central nucleus of the amygdala. Our findings
      point out a prominent role for catecholaminergic and peptidergic pathways in the
      brain in response to systemic nitroglycerin.

PMID- 8735972
TI  - Specificity of proteolysis inhibitors in rabbit plasma.
AB  - Hydrolysis and inhibition of hydrolysis of leucine enkephalin in Oryctolagus
      plasma were studied by kinetics and chromatographic techniques. By data obtained,
      in this species, enkephalins are degraded by the same enzymes active in other
      mammals: aminopeptidases, dipeptidylaminopeptidases, and
      dipeptidylcarboxypeptidases. At variance with data obtained in other species,
      where enkephalins are hydrolyzed mostly by aminopeptidases, in Oryctolagus Leu
      enkephalin hydrolysis is mainly due to dipeptidylcarboxypeptidases, whereas
      aminopeptidases contribution is the minimum of all three enzyme groups.
      Comparative analyses performed in the presence and in the absence of plasma
      inhibitors indicate that the ability of these substances to reduce substratum
      hydrolysis is very limited. On the contrary, the specific hydrolysis pattern
      evidenced appears to originate primarily from selective inhibition of the three
      groups of enzymes. Results obtained appear consistent with a role of plasma
      inhibitors in tuning hydrolysis to specific substrata, without appreciably
      modifying the amount of the substratum degraded.

PMID- 8735974
TI  - The interaction of vasopressin and the photic oscillator in circadian rhythms.
AB  - Telemetered body temperature (BT), heart rate (HR), and activity (AC) data were
      collected in vasopressin-containing Long-Evans (LE) and vasopressin-deficient
      Brattleboro (DI) rats. The rats were exposed to a 12/12 h light/dark cycle under
      three conditions: 1) ad lib feeding throughout the 24-h cycle, 2) two scheduled
      feeding periods during the diurnal component of the light/dark cycle, and 3) two
      scheduled-feeding periods during the nocturnal component of the light/dark cycle.
      With ad lib feeding, natural nocturnal cycles of BT, HR, and AC were maintained
      in both strains. Marked changes were observed under the condition of scheduled
      feeding during the diurnal component of the light/dark cycle. In DI animals the
      influence of the photic oscillator was lost and BT, HR, and AC shifted from
      nocturnal to diurnal patterns. Circadian rhythms in DI animals were now
      synchronized by the nonphotic zeitgeber of scheduled food presentation. On the
      other hand, LE animals lost a well-defined circadian rhythmicity resulting from
      adherence to the photic oscillator, while at the same time being influenced by
      the nonphotic oscillator. Under the condition of scheduled feeding during the
      nocturnal component of the light/dark cycle, the circadian rhythms were similar
      in DI and LE rats. Results show that vasopressin has a significant interaction
      with the photic oscillator, which is obvious only when the photic and nonphotic
      oscillators are uncoupled. In addition, the results demonstrate that the strength
      of the photic oscillator is decreased or that the effect of this oscillator is
      masked or lost in DI rats compared to LE rats.

PMID- 8735973
TI  - Adrenotensin: an adrenomedullin gene product contracts pulmonary blood vessels.
AB  - The purpose of the present study was to determine the effects of adrenotensin, a
      newly described product of the ADM gene, on cat pulmonary arterial (PA) rings.
      Under resting conditions, adrenotensin increased tension of PA rings in a
      concentration-dependent manner. Although addition of diphenhydramine, ONO-3708,
      phentolamine, methysergide, atropine, and meclofenamate did not alter the
      contractile response to adrenotensin, removal of the endothelial cell layer
      significantly reduced this response. Moreover, precontraction of PA rings with
      adrenotensin selectively attenuated the pulmonary vasorelaxant response to ADM
      but not to other vasodilator substances, including isoproterenol, pinacidil,
      nifedipine, and adenosine. The present data suggest that adrenotensin acts in an
      endothelium-dependent manner to contract PA rings. Moreover, the present data
      suggest that adrenotensin may act in a modulatory manner to influence
      vasorelaxation in response to ADM, a sister proADM product.

PMID- 8735975
TI  - Evidence for expression of vasopressin V2 receptor mRNA in human lung.
AB  - Studies using fetal sheep, goats, and guinea pigs indicate that vasopressin may
      play a role in preparing the fetal lung for the transition from a uterine to an
      air-breathing environment by slowing lung liquid secretion. The mechanism of
      vasopressin action is believed to occur through V2 receptors with subsequent
      activation of amiloride-sensitive sodium channels. However, the presence of the
      V2 receptor in human lung has not yet been documented. In the present study,
      expression of the vasopressin V2 receptor in fetal and adult human lung was
      examined using reverse transcription-polymerase chain reaction (RT-PCR), Northern
      blot analysis, and DNA sequencing. Using RT-PCR and primer pairs specific for the
      human V2 receptor, PCR products of the predicted sizes of 512 and 862 bp were
      obtained from adult human lung. DNA sequencing of the cloned PCR products
      revealed exact identity with the published sequence for the V2 receptor. Northern
      blot analysis revealed the expression of a approximately 1.9 kb mRNA in adult
      human lung as well as in kidney, but not in fetal human lung at 22-24 weeks of
      gestation. However, using the more sensitive RT-PCR assay the 862-bp product was
      successfully amplified from human fetal lung, although the data indicate the mRNA
      for this receptor is expressed in lower levels than in adult human lung or
      kidney. Using RT-PCR and primers specific for the rat V2 receptor, a PCR product
      of the predicted size of 461 bp was amplified from adult rat lung and kidney,
      despite an earlier report that this receptor mRNA is absent from the lung of this
      species. The role for the V2 receptor in adult human lung is unknown at this
      time, but, as in the human kidney and lungs of fetal sheep, goats, and guinea
      pigs, this receptor may play a role in fluid balance.

PMID- 8735977
TI  - Locations and molecular forms of gastrin-releasing peptide-like immunoreactive
      entities in ovine pregnancy.
AB  - Large quantities of gastrin-releasing peptide-like immunoreactivity (GRP-LI) are
      present in ovine pregnancy fluids (allantoic fluid > fetal plasma > esophageal
      fluid = amniotic fluid = urine > maternal plasma) and in term endometrium (60 +/-
      29 pmol.g-1) and myometrium (4.5 +/- 1.2 pmol.g-1). The larger molecular size
      [greater than GRP (1-27)] of this GRP-LI entity is not due to a GRP binding
      protein nor to a C-terminal extension of GRP. In contrast, ovine fetal colon
      extracts appear to contain the usual GRP (1-27) and GRP (18-27) forms. Hence, the
      uterus, not the fetus, is the probable source of this novel GRP-like peptide. It
      apparently acts as a hormone in ovine pregnancy and may play an important role in
      fetal-placental development.

PMID- 8735976
TI  - Several roles of CCKA and CCKB receptor subtypes in CCK-8-induced and LiCl
      induced taste aversion conditioning.
AB  - Administration of a relatively large IP dose of sulfated cholecystokinin (26-33)
      (CCK-8; 1.0 mumol/kg) consistently induced moderate taste aversion conditioning
      (TAC) using a 20-min, one-bottle test in Long-Evans rats. Because CCK-8 has
      affinity for both CCKA and CCKB receptor subtypes, we wanted to determine the
      subtype involved in CCK-8-induced TAC. Pretreatment with the selective CCKA
      antagonist MK-329 (L-364, 718 or devazepide), at doses of 0.1, 1.0, or 10.0
      mumol/kg, markedly antagonized (> 70%) CCK-8-induced TAC. Pretreatment with the
      selective CCKB antagonist L-365,260, at doses of 0.1 or 1.0 mumol/kg, partially
      antagonized (approximately 50%) CCK-8-induced TAC, although the highest dose of L
      365,260. 10.0 mumol/kg, did not. These partial antagonistic effects of L-365,260
      on CCK-8-induced TAC were replicated in our second study. In our third study, we
      observed that another CCKB antagonist, the dipeptoid CI-988, also partially
      antagonized CCK-8-induced TAC at a dose of 0.1, but not 1.0 or 10.0, mumol/kg. In
      our final study, pretreatments with a single dose (i.e., 10.0, but not 0.1 or
      1.0, mumol/kg) of either MK-329 or L-365,260 were also shown to partially
      antagonize the formation of moderate TAC induced by treatment with LiCl at 708
      mumol/kg. Marked antagonism of LiCl-induced TAC was also observed following
      pretreatment with the known anxiolytic chlordiazepoxide HCl at 7.4 mumol/kg.
      Considering the existing data on the induction of TAC by various CCK analogues,
      we consider an action of CCK-8 on peripheral CCKA, but not CCKB, receptors
      necessary for the induction of TAC. Our results of partial antagonism of CCK-8-
      and LiCl-induced TAC by L-365,260, CI-988, or MK-329 suggest, but do not prove,
      that both CCKA and CCKB mechanisms may be operative during TAC. Because the CCK
      antagonists affected TAC like chlordiazepoxide, blockade of CCKA and CCKB
      mechanisms may produce a mild anxiolytic effect.

PMID- 8735978
TI  - Amylin mobilizes [Ca2+]i and stimulates the release of pancreatic digestive
      enzymes from rat acinar AR42J cells: evidence for an exclusive receptor system of
      amylin.
AB  - Amylin dose-dependently stimulated the secretion of amylase and cholesterol
      esterase from rat pancreatic acinar AR42J cells. The biochemical basis of this
      action was investigated using fura-2-loaded AR42J cells. Amylin increased
      intracellular free calcium. [Ca2+]i, in a dose-dependent manner. The Ca2+ signal
      persisted even in Ca(2+)-free medium, suggesting mobilization from intracellular
      stores rather than influx. Consistently, thapsigargin abolished amylin-induced
      responses, suggesting that Ca2+ is released from an inositol 1,4,5-triphosphate
      (IP3)-sensitive pool. This was confirmed by the finding that amylin elevated IP3
      levels. AR42J cells pretreated with amylin did not respond to amylin, suggesting
      that the receptors mediating this response undergo homologous desensitization.
      However, pretreatment with related peptides, calcitonin gene-related peptide
      (CGRP) and salmon calcitonin, did not diminish [Ca2+]i mobilization by amylin.
      CGRP and calcitonin also failed to mobilize [Ca2+]i even at 10 microM. These
      results suggests that the stimulatory effects of amylin on pancreatic digestive
      enzyme secretion from AR42J cells are mediated by a G-protein-linked membrane
      receptor coupled to IP3-dependent calcium pools.

PMID- 8735979
TI  - Immunohistochemical identification and effects of atrial natriuretic peptide,
      pancreastatin, leucine-enkephalin, and galanin in the porcine pancreas.
AB  - This study demonstrates the presence and distribution of atrial natriuretic
      peptide (ANP) pancreastatin (PST), leucineenkephalin (Leu-ENK), galanin (GAL),
      and insulin in the pig pancreas. The effects of PST, ANP, Leu-ENK, and GAL on
      protein and amylase secretion were also investigated to determine their
      functional role in the control of pancreatic secretion. PST-immunoreactive cells
      were observed in the islet of Langerhans and in the wall of the ducts. Leu-ENK
      immunopositive cells were observed in both the endo-and exocrine pancreas. It is
      colocalized with insulin in the islet of Langerhans. ANP immunoreactivity was
      discernible in nerve fibers and cells of the exocrine pancreas. GAL
      immunopositive cells were observed in close association with insulin-positive
      cells in the islets of Langerhans and in the exocrine pancreas. Stimulation of
      isolated pancreatic segments with either ANP or Leu-ENK resulted in increased
      protein secretion and amylase output. The Leu-ENK-evoked amylase secretion was
      antagonized by naloxone. Pancreastatin was effective at all concentrations, but
      low concentration had more marked secretory effects whereas GAL failed to evoke
      any significant increases in either protein or amylase secretion. The results of
      the study have demonstrated a close association of peptidergic fibers with the
      secretory cells of the pancreas. The nerve fibers can release peptides that in
      turn can stimulate protein and amylase secretion.

PMID- 8735980
TI  - Peripherally administered calcitonin gene-related peptide decreases food intake
      in mice.
AB  - Previously, calcitonin gene-related peptide (CGRP) decreased food intake when
      administered ICV but not when administered peripherally to rats. Amylin, which
      has a close structural homology to CGRP, reduced food intake administered IP at
      concentrations higher than those previously tested for CGRP. We examined the
      effects of higher doses of IP-administered CGRP on food intake. CGRP reduced food
      intake from 25 to 200 micrograms/kg in mice. CGRP did not reduce water intake and
      was not aversive in a two-bottle test. Using a lever press, CGRP was more
      effective at reducing milk consumption in prefed than in nonprefed mice. The
      effect of CGRP on food intake was not antagonized by the cholecystokinin A
      receptor antagonist, L364,718. These studies suggest a role for CGRP as a
      satiating factor.

PMID- 8735981
TI  - Neuropeptide Y blocks and reverses interleukin-1 beta-induced anorexia in rats.
AB  - Neuropeptide Y (NPY) increases feeding by direct action in the central nervous
      system (CNS). Interleukin-1 beta (IL-1 beta), on the other hand, induces anorexia
      when administered ICV at estimated pathophysiological (e.g., yielded by 1.0
      ng/rat dose) and pharmacological (> or = 4.0 ng) concentrations in the
      cerebrospinal fluid (CSF). In the present study, we investigated NPY/IL-1 beta
      interactions using the ICV administration. ICV microinfusion of NPY (5.0
      micrograms) significantly increased 2-h food intake (by 89%), whereas IL-1 beta
      decreased 2-h food intake (32% decrease with 1.0 ng/rat; 53% with 4.0 ng/rat; and
      51% with 8.0 ng/rat). NPY (5.0 micrograms) blocked the anorexic effect induced by
      all doses of IL-1 beta when both compounds were administered concomitantly.
      Central infusion of NPY was also able to induce feeding in IL-1 beta-pretreated
      rats exhibiting marked anorexia. The results show that ICV-administered NPY
      blocks and reverses the anorexia induced by estimated pathophysiological and
      pharmacological concentrations of IL-1 beta in rats. A second interpretation of a
      data subset is that IL-1 beta attenuates or blocks NPY-induced increase in
      feeding depending on the IL-1 beta dose used. Blockage and reversal of IL-1 beta
      induced anorexia by NPY suggest the importance in studying cytokine-peptide
      interactions in the regulation of feeding behavior. Understanding these
      endogenous interactions may produce strategies with potential therapeutic
      implications for chronic diseases associated with long-term anorexia.

PMID- 8735982
TI  - Endothelin receptor synthetic N-terminal fragment interacts with the receptor
      itself.
AB  - Endothelin binds to receptors belonging to the family of G-protein-coupled
      receptors with an N-terminal extracellular domain that is suspected to be part of
      the binding site. We have synthesized different peptides of this N-terminal
      extracellular domain and analyzed the increase in calcium concentration ([Ca2+]i)
      induced by these peptides in the MEG-01 cell line and their influence on the ET-1
      concentration-effect response. Nt (20-79) exhibited a partial agonistic effect on
      [Ca2+]i and blunted the functional response of ET-1 in MEG-01 cells, but was not
      able to compete with radiolabeled ET-1 binding. The agonist effect was inhibited
      by the ET receptor antagonists PD 142893 and BQ123, suggesting an interaction
      between Nt (20-79) and the ETA receptor at a site that could be different from
      the one of ET-1.

PMID- 8735983
TI  - Production of [Asn1, Val5] angiotensin II and [Asp1, Val5] angiotensin II in
      kallikrein-treated trout plasma (T60K).
AB  - Incubation of heat-denatured plasma from the rainbow trout Oncorhynchus mykiss
      with porcine pancreatic kallikrein generates, in addition to bradykinin-related
      peptides, previously uncharacterized peptides that contract mammalian and
      amphibian vascular smooth muscle. Using rings of vascular smooth muscle from the
      bullfrog systemic arch as bioassay, we have isolated two myotropic peptides whose
      primary structures were established as: Asn-Arg-Val-Tyr-Val-His-Pro-Phe ([Asn1,
      Val5]angiotensin II) and Asp-Arg-Val-Tyr-Val-His-Pro-Phe ([Asp1, Val5]angiotensin
      II). These peptides are the same as those generated in salmon plasma by an
      extract of kidney. The data raise the possibility that activation of the
      kallikrein-kinin system in trout generates both bradykinin-related and
      angiotensin II-related peptides that may act synergistically in the regulation of
      blood pressure.

PMID- 8735984
TI  - Isolation and cardiovascular activity of a second bradykinin-related peptide
      ([Arg0, Trp5, Leu8]bradykinin) from trout.
AB  - Previous work has shown that incubation of heat-denatured plasma from the rainbow
      trout Oncorhynchus mykiss with porcine pancreatic kallikrein generates [Lys0,
      Trp5, Leu8]bradykinin (trout [Lys0]BK). We have now isolated a second BK-related
      peptide from kallikrein-treated trout plasma with the primary structure: Arg-Arg
      Pro-Gly-Trp-Ser-Pro-Leu-Arg (trout [Arg0]BK). Bolus injections of both trout
      [Arg0]BK and [Lys0]BK (> 100 pmol/kg) into the dorsal aorta of conscious trout
      produced multiphasic effects on arterial blood pressure. An initial pressor
      response of short duration (1-2 min) was followed by a fall in pressure (to below
      basal values in 11 out of 15 animals) and then by a sustained rise in pressure
      lasting up to 60 min. The maximum rise in pressure produced by trout [Arg0]BK (10
      nmol/kg) was approximately one-fourth of the maximum rise produced by angiotensin
      II in the same animals. Intracerebroventricular injections of trout [Arg0]BK (500
      pmol) into conscious trout had no effect on arterial blood pressure or heart
      rate. Trout [Arg0]BK did not affect the tension of vascular rings from trout
      efferent branchial and caeliacomesenteric arteries and anterior cardinal vein.
      Trout des [Arg9]BK had no effect on cardiovascular parameters, either in vivo or
      in vitro, indicating that the C-terminal arginine residue of the peptide is
      important in interaction with the trout kinin receptor(s).

PMID- 8735985
TI  - Intravenous NPY (27-36)-D decreases cardiac output in conscious Sprague-Dawley
      rats.
AB  - Intravenous (IV) administration of NPY (27-36)-D, a substituted carboxyterminal
      fragment of neuropeptide Y (NPY), decreases mean arterial pressure (MAP) in normo
      and hypertensive rats by a mechanism partially involving histamine receptors. The
      purpose of this study is to further characterize the cardiovascular effects of
      NPY (27-36)-D. NPY (27-36)-D dose-dependently decreased MAP, cardiac output, and
      stroke volume without significantly altering peripheral resistance. Myocardial
      contractility diminished by 151.2 +/- 31.8, 529.6 +/- 182.5, and 495.4 +/- 66.7
      mmHg/s2 in rats treated with 300, 500, and 750 nmol/kg NPY (27-36)-D,
      respectively. Therefore, NPY (27-36)-D modifies MAP, in part, by a reversible
      negative inotropic effect on the heart.

PMID- 8735986
TI  - Peptides and growth factors in non-small cell lung cancer.
AB  - Numerous growth factors and receptors that alter proliferation have been
      identified in lung cancer. In non-small cell lung cancer (NSCLC) cell lines, high
      levels of vasoactive intestinal peptide (VIP) mRNA have been detected by Northern
      analysis, and immunoreactive VIP is present. VIP elevates intracellular cAMP and
      stimulates the clonal growth of NSCLC cells. Also, transforming growth factor
      alpha (TGF-alpha) mRNA is present in NSCLC cells and TGF-alpha is present in
      conditioned media exposed to NSCLC cells. TGF-alpha binds with high affinity to
      epidermal growth factor (EGF) receptors present on NSCLC cells. EGF stimulates
      tyrosine kinase activity and growth in NSCLC cells. Synthetic peptide antagonists
      and monoclonal antibodies have been identified that disrupt autocrine growth
      pathways and inhibit NSCLC growth. These data suggest that VIP and TGF-alpha are
      important autocrine growth factors for NSCLC.

PMID- 8735987
TI  - H-Lys-Arg-Asn-Lys-Asn-Asn-OH is the minimal active structure of oxyntomodulin.
AB  - Oxyntomodulin inhibits gastric acid secretion via its C-terminal octapeptide. Its
      minimal active structure was delineated by testing, on histamine-stimulated
      gastric acid secretion in the conscious rat, the inhibitory effect of octapeptide
      analogues, shortened either or both on their N- or C- terminus. The octapeptide
      may be simplified by deleting the two C-terminal amino acids while keeping its
      efficacy and the slope of the dose-response curve. Suppressing the first N
      terminal amino acid dramatically decreased the activity. The nonprotected
      peptides are metabolized by aminopeptidases and endopeptidases. The increased
      potency of the N-acetylated forms is related, at least in part, with their
      protection against aminopeptidases.

PMID- 8735988
TI  - The effect of human calcitonin gene-related peptide on eosinophil chemotaxis in
      the rat airway.
AB  - Eosinophils play a key role for the function of release inflammatory mediators
      and destroy epithelial tissue in the airway. Therefore, they have been accepted
      to be proinflammatory effector cells in the pathogenesis of the bronchial asthma.
      The aim of this study was to investigate the effect of the calcitonin gene
      related peptide (CGRP) a 37-amino acid neuropeptide on eosinophils responsible
      for hypersensitivity using BAL fluids that represent the cell population in the
      lung tissue. For this purpose, 15 rats were divided into three groups receiving
      vehicle, 10(-6) M and 10(-5) M CGRP using a portable nebulizer. Nebulated
      exposure of CGRP resulted in both significant increases in the eosinophil numbers
      with 10(-6) and 10(-5) M CGRP of 18 +/- 0.913 cell/mm2 (mean +/- SEM: p < 0.01)
      and 31.25 +/- 1.931 (p < 0.01), respectively vs. control (12 +/- 0.408 cell/mm2).
      CGRP is capable of causing a eosinophilia in the lung in vivo and may contribute
      to airway inflammation in patients with asthma.

PMID- 8735989
TI  - Thomas K. Cureton, Jr.: pioneer researcher, proselytizer, and proponent for
      physical fitness.

PMID- 8735990
TI  - Predicting self-esteem from perceptions of actual and ideal ratings of body
      fatness: is there only one ideal "supermodel"?
AB  - Silhouette ratings of actual and ideal body fat (N = 258 high school students)
      were related to 4 self-concept scales (Body Fat, Physical Appearance, General
      Physical, Esteem) and objective body composition measures in order to test
      predictions from actual-ideal discrepancy models. Actual-ideal discrepancy scores
      were more strongly related to self-concept than actual scores alone, thus
      supporting the traditional discrepancy model. However, multiple regression
      analyses demonstrated that more sophisticated actual-ideal discrepancy models
      that considered discrepancies in either direction (feeling too fat or too thin)
      did significantly better. Because the traditional discrepancy model is a special
      case of this more general discrepancy model, the more general model should have
      broad applicability. Important aspects of this task were (a) that discrepancies
      were evaluated along a continuum in which the ideal was not one of the endpoints
      of the continuum, (b) that there was reasonable variation in ideal ratings, and
      (c) that positive and negative discrepancies were reported.

PMID- 8735991
TI  - Many-faceted Rasch calibration of a gross motor instrument.
AB  - The purpose of this study was to recalibrate a well-developed motor development
      instrument (Ulrich, 1985) using the many-faceted Rasch model and to examine its
      advantages and application potential. The instrument was administered to a total
      of 909 children from a national multistage sampling across 9 states. These
      children included 451 boys and 458 girls ranging in age from 3-10 years. The
      instrument was recalibrated using the many-faceted Rasch model with 8 defined
      facets. The primary advantages of the many-faceted Rasch calibration are (a) that
      estimations of parameters are independent of both the examinees and testing items
      employed, (b) that all facets involved in the calibration can be taken into
      account, (c) that the calibrated facets share the same metric, and (d) that the
      measurement scales are additive. These advantages, together with goodness-of-fit
      statistics generated from the calibration, provided a convenient way to examine
      the appropriateness of the testing items and related facets and to determine
      examinees' strengths and weaknesses of their measured ability. Finally, through a
      step-by-step example, it was shown that applying the many-faceted Rasch
      calibrated instrument can be both simple and practical.

PMID- 8735992
TI  - The benefits of random variable practice for spatial accuracy and error detection
      in a rapid aiming task.
AB  - The role of blocked and random variable practice in the development of a spatial
      error detection mechanism in 2 experiments was investigated in the present study.
      Twenty-four (Experiment 1) and 40 (Experiment 2) college-aged participants made
      either 20, 40, 60 degrees quick lever reversal movements in the sagittal plane.
      During acquisition in both experiments, blocked practice resulted in less spatial
      absolute constant error (ICEI) relative to the random group. The blocked practice
      group showed a smaller mean absolute objective-subjective difference than the
      random practice group during acquisition (Experiment 1). On no-knowledge of
      results retention tests in both studies, the random practice group showed a
      smaller spatial ICEI and a smaller mean absolute objective-subjective difference
      than the blocked practice group, even on a novel amplitude (Experiment 2). The
      study demonstrated the advantage of random variable practice over blocked
      variable practice on retention tests for spatial performance and in developing a
      spatial error detection capability.

PMID- 8735993
TI  - Ensenanzas en un gimnasio: an investigation of modeling and verbal rehearsal on
      the motor performance of Hispanic limited English proficient children.
AB  - This study investigated the effects of modeling and verbal rehearsal on the motor
      performance of English-speaking and limited English proficient (LEP) children.
      Children (N = 64) in 4th-grade classes were randomly assigned to conditions in a
      2 x 2 x 2 x 2 (Gender x Primary Language x Model Type x Rehearsal) factorial
      design. Boys and girls whose primary language was English or Spanish were
      assigned to either a verbal model or no-model condition as well as to a verbal
      rehearsal or no-rehearsal condition of the motor skills required to be performed.
      Analysis of variance revealed a significant Model Type x Primary Language
      interaction as well as a significant Rehearsal x Primary Language interaction.
      Follow-up analyses revealed that English-speaking children provided with a verbal
      rehearsal strategy recalled significantly more skills than English-speaking
      children in the no-rehearsal condition; for LEP children, there were no
      differences due to rehearsal. Moreover, LEP children presented with a verbal
      model recalled significantly more skills than LEP children in the no-model
      condition; for English-speaking children, there were no differences attributed to
      model type. These results indicate that effective modeling conditions that are
      provided with verbal cues in English are related to children's primary language.

PMID- 8735994
TI  - Practice schedule effects on the performance and learning of low- and high
      skilled students: an applied study.
AB  - This study examined the effects of practice schedule manipulations implemented in
      an instructional setting on the performance and learning of low- and high-skilled
      students. College undergraduates (N = 83) enrolled in 5 tennis classes completed
      a pretest on the forehand and backhand ground strokes, practiced these skills
      under a blocked or alternating schedule, and then completed a posttest. Results
      indicated that practice schedule effects on learning were influenced by student
      ability. Low-skilled students assigned to the blocked schedule had higher
      posttest scores than those assigned to the alternating schedule, whereas no
      significant differences were found for high-skilled students. These findings are
      discussed in relation to previous applied and laboratory-based findings and as a
      means for manipulating practice difficulty in teaching physical education.

PMID- 8735995
TI  - The contextual interference effect in parameter modifications of the same
      generalized motor program.
AB  - This study extended previous work (Sekiya, Magill, Sidaway, & Anderson, 1994) by
      examining whether the contextual interference (CI) effect could be found when
      task variations were controlled by the same generalized motor program (GMP) but
      differentiated on the basis of overall force parameter modifications. A
      subsidiary aim of this study was to determine how the amount of practice
      influenced the CI effect. During 2 acquisition sessions and 2 retention sessions,
      participants (N = 24) performed 3 task variations in either a blocked (low CI) or
      serial (high CI) condition. The task variations shared the same relative force
      structures but differed in the amount of overall force that had to be produced.
      Analysis of a general error measure revealed a strong CI effect, indicating that
      overall force parameter modifications of the same GMP created the CI effect.
      Analyses of various dependent measures, which dissociated GMP from parameter
      components with regard to force characteristics, revealed that parameter
      learning, but not GMP learning, was enhanced by high CI practice. No CI effect
      occurred in any aspect of timing characteristics. The amount of practice used in
      the present study did not influence the efficacy of the CI effect.

PMID- 8735996
TI  - Specificity of learning and dynamic balance.
AB  - Contrary to a strict specificity of learning position, Robertson, Collins,
      Elliott, and Starkes (1994) have reported that the balance beam performance of
      expert gymnasts is less affected by the withdrawal of vision than is the
      performance of novice gymnasts. In this study, we employed a training paradigm in
      order to exercise complete control over the sensory conditions under which a
      dynamic balance beam task was acquired. Novice participants were trained either
      with or without vision to walk across a balance beam as quickly as possible and
      later tested in the other vision condition. Although participants improved more
      in the condition in which they trained, practice in one sensory condition did not
      negatively affect performance in a different sensory circumstance. The finding
      that vision was still extremely important after 5 days of practice is problematic
      for models of motor learning that propose a progression with learning from closed
      loop to open-loop control.

PMID- 8735997
TI  - Toward a conceptual understanding of the flow experience in elite athletes.
AB  - An in-depth investigation into flow state was conducted in order to understand
      how this optimal state is experienced by elite athletes. Twenty-eight elite-level
      athletes, representing 7 sports, were interviewed on their perceptions of flow
      state during performance of their sport. Csikszentmihalyi's (1990) model of the
      flow state was examined for its applicability to elite athletes. Correspondence
      was found between the dimensions of flow, as described by Csikszentmihalyi
      (1990), and the athletes' descriptions of their experience of flow; some
      dimensions received greater support through the qualitative analysis of the
      athletes' descriptions than did other dimensions. Those dimensions of flow most
      represented across the group's data were the autotelic experience of flow, total
      concentration on the task at hand, merging of action and awareness, and the
      paradox of control. The analyses provided a detailed, sport-specific picture of
      flow state in elite athletes.

PMID- 8735998
TI  - EEG power spectral densities during and after cycle ergometer exercise.
AB  - This study examined the effects of aerobic exercise on spontaneous
      electroencephalographic (EEG) activity. Participants (N = 34) were asked to (a)
      sit quietly for a 10-min adaptation period, (b) either exercise on a cycle
      ergometer (n = 18) or watch a videotape (n = 16) for 15 min, and (c) sit quietly
      for a 10-min recovery period. EEGs were collected during the last 2 min of the
      adaptation period, the last 2 min of each 5-min stage of the exercise/videotape
      period, and the last 2 min of the recovery period. EEG power densities were
      combined across the alpha and beta frequency bands. The results indicated that
      brain activation increased (i.e., alpha activity decreased and beta activity
      increased) during the exercise condition and returned to baseline following
      exercise. This did not occur in the nonexercise condition. Thus, the results were
      consistent with the opponent-process theory (Solomon, 1980) in that brain
      activation increased during exercise.

PMID- 8735999
TI  - Stride adjustments during a running approach toward a force plate.

PMID- 8736000
TI  - Aerobic demand of running shoes designed to exploit energy storage and return.

PMID- 8736001
TI  - The visual instruction system.

PMID- 8736002
TI  - The effect of exercise on the decision-making performance of experienced and
      inexperienced soccer players.

PMID- 8736003
TI  - Reliability of the prudential FITNESSGRAM trunk lift test in young adults.

PMID- 8736004
TI  - Beat-to-beat variability of left ventricular indexes measured by acoustic
      quantification: influence of heart rate and respiration--correlation with M-mode
      echocardiography.
AB  - Influence of heart rate and respiration on beat-to-beat variability of left
      ventricular indexes measured by acoustic quantification was examined. These
      indexes were correlated with their counterparts measured by M-mode
      echocardiography. Parameters of left ventricular performance were recorded for 1
      full minute in 43 children with a mean age of 5.9 +/- 3.9 years. Beat-to-beat
      variability was documented. The effect of respiration on such variability was
      examined in another 10 subjects. A wide range of heart rates and respiration did
      not show significant influence on the degree of variance among these parameters.
      The indexes measured correlated well with their counterparts measured by M-mode
      echocardiography. Acoustic quantification separated those with normal from those
      with abnormal left ventricular function with the same statistical significance as
      did M-mode echocardiography. A moderate degree of beat-to-beat variability occurs
      in acoustic quantification-derived left ventricular indexes. Heart rate
      variability and respiration do not influence the beat-to-beat variance of
      parameters of left ventricular performance measured with the acoustic
      quantification. Excellent correlation was documented between this technique and M
      mode echocardiography.

PMID- 8736005
TI  - Assessment of the Frank-Starling relationship by two-dimensional
      echocardiography.
AB  - The Frank-Starling relationship between left ventricular stroke work and end
      diastolic minor-axis cross-sectional area was evaluated as a load-insensitive
      measure of inotropic state by two-dimensional echocardiography in 10 conscious
      dogs. Stroke work was calculated as the product of systolic change in cross
      sectional area and either (1) beat-to-beat mean arterial pressure or (2) initial
      systolic blood pressure. Both Frank-Starling relationships were highly linear
      during preload variation (mean r = 0.96), sensitive to the inotropic state (slope
      increase with calcium 51% +/- 43% and 62% +/- 53%, respectively), and insensitive
      to afterload (r < 0.4, slope or x intercept versus afterload). Thus the Frank
      Starling relationships derived from two-dimensional echocardiographic images and
      peripheral arterial pressure may be a useful and practical means of assessing
      inotropic state with minimally invasive measurements.

PMID- 8736006
TI  - Doppler echocardiographic evaluation of left ventricular end-diastolic pressure
      in patients with coronary artery disease.
AB  - Pulmonary venous flow velocity recordings have been found to be useful in
      complementing the information obtained from the mitral flow velocity and
      improving the assessment of left ventricular diastolic pressures. This study was
      undertaken to evaluate the accuracy of mitral flow and pulmonary venous flow
      variables, recorded by transthoracic Doppler echocardiography, in estimating left
      ventricular end-diastolic pressure (LVEDP) in 101 consecutive patients with
      coronary artery disease undergoing diagnostic left-sided heart catheterization.
      Patients were assigned to three groups according to the values of LVEDP (group 1,
      < or = 12 mm Hg; group 2, between 13 and 19 mm Hg; and group 3, > or = 20 mm Hg).
      LVEDP correlated most strongly with systolic fraction of pulmonary venous flow (r
      = -0.76), isovolumic relaxation time (r = -0.76), E/A ratio (r = 0.74),
      deceleration time of early mitral flow (r = -0.74), and mitral A wave
      duration/pulmonary venous A wave duration (AD/PVAD) ratio (r = -0.70) (p < 0.01
      for each correlation). Discriminant analysis demonstrated that deceleration time,
      AD/PVAD ratio, and isovolumic relaxation time were major determinants of LVEDP,
      with 87.1% of patients correctly assigned to study groups; 97% of patients of
      group 1 and 95% of patients of group 3 were identified, whereas the accuracy in
      identifying the patients of group 2 was lower (41%). Deceleration times of 140
      msec or less and AD/PVAD ratios of 0.9 or less were the best cutoff points in
      predicting an LVEDP of 20 mm Hg or greater. Multiple linear regression analysis
      demonstrated that the combination of mitral flow and pulmonary venous flow
      velocity variables provided a better estimation of LVEDP compared with that
      obtained from mitral flow velocity recordings alone (r = 0.88 versus 0.79; F
      test, 20.6). We conclude that combined analysis of mitral flow and pulmonary
      venous flow velocity provides, in patients with coronary artery disease, a
      noninvasive estimation of LVEDP with an accurate prediction of pressures of 12 mm
      Hg or less and 20 mm Hg or greater and less accurate prediction of intermediate
      values.

PMID- 8736007
TI  - Short- and long-term variability of echocardiographic stress-velocity indexes of
      cardiac function in a pediatric population.
AB  - This study determined the short- and long-term variability of stress-velocity
      relationships at end systole and peak systole. A prospective study during the
      short term (0 to 15 and 0 to 30 minutes) and long term (0 to 1 and 0 to 12
      months) was performed calculating variability by the limits of agreement method.
      The study was performed in a tertiary-care pediatric echocardiographic
      laboratory. Twenty-five normal children underwent repeat testing as described.
      Standard blood pressure, carotid pulse tracing, and M-echocardiography of the
      left ventricle was performed at the intervals described. The rate-corrected mean
      velocity of fiber shortening (MVCFC), echocardiographic stress at end systole
      (SES), and echocardiographic stress at peak systole (SPS) were calculated for all
      recordings. The slopes of MVCFC-SES and MVCFC-SPS were determined by regression
      and plotted. With these slopes, the second and third stress values were
      normalized to the first stress value for the short and long term. The differences
      in normalized MVCFC and MVCFC (delta MVCFC) for 15 to 0 minutes, 30 to 0 months,
      1 to 0 month, and 12 to 1 month were obtained for both SES and SPS, and 95%
      limits of agreement were estimated. The mean delta MVCFC for SES and SPS for the
      short and long term were not different from 0 or each other, indicating no bias.
      The 95% limits of agreement of delta MVCFCs (i.e., variability for SES at 15 to 0
      minutes, 30 to 0 minutes, 1 to 0 month, and 12 to 0 month) were +/- 0.18, +/-
      0.24, +/- 0.34, and +/- 0.27, respectively, and for SPS +/- 0.18, +/- 0.24, +/-
      0.33, and +/- 0.28. Variability showed an increasing trend with time but was
      significant only from 15 to 0 minutes and 1 to 0 month (p = 0.006). This study
      has established short- and long-term variability in the stress-velocity
      relationship that is essential for monitoring acute and chronic changes in
      ventricular contractility in an individual patient.

PMID- 8736008
TI  - A systematic approach to echocardiographic image acquisition and three
      dimensional reconstruction with a subxiphoid rotational scan.
AB  - Rotational scanning from the subxiphoid position is an image acquisition
      technique used for reconstruction of dynamic three-dimensional echocardiographic
      images in infants and small children. The orientation of the heart within the
      three-dimensional data set is variable and dependent on the image plane at which
      rotational scanning was initiated. We describe an image acquisition technique
      that standardizes the orientation of the heart within the three-dimensional data
      set, thereby permitting a systematic approach to the reconstruction of three
      dimensional renderings. Thirteen infants and small children with congenital heart
      disease were studied by this approach. Illustrative examples are provided. The
      average time required to derive a three-dimensional rendering was 37 +/- 9
      minutes. We conclude that subxiphoid rotational scanning by a systematic approach
      to image acquisition and reconstruction can be applied successfully to the
      derivation of three-dimensional renderings of congenital cardiac defects.

PMID- 8736009
TI  - How positionally stable is a transesophageal echocardiographic probe?
      Implications for three-dimensional reconstruction.
AB  - Three-dimensional (3D) reconstruction from a single esophageal scanning position
      requires a stable relationship between the probe and the heart. The purpose of
      this study was to examine the movement of a transesophageal echocardiographic
      probe during 3D image acquisition. A new dual-axis multiplane probe was used that
      includes a miniature (6 x 6 x 9 mm) magnetic sensor in the tip. The sensor
      identifies the probe's 3D position and 3D orientation in space with respect to
      the location of a magnetic field generator placed beneath the subject. In vivo 3D
      scanning was performed in five anesthetized, ventilated dogs, with positional
      determinations acquired every 66 msec. Probe movement was estimated by computing
      the deviations of each x, y, and z position and orientation determination,
      compared with the average values during each 3D scan or cardiac cycle. Ten 3D
      scans were analyzed, involving 263 cardiac cycles and 2328 determinations. The
      range and SD of the translational movement of the transducer were 2.3 and 0.8 mm,
      1.7 and 0.5 mm, and 2.4 and 0.7 mm in x, y, and z directions, respectively,
      during 3D scanning. Translational movement was more dominant than was rotational
      movement. Misregistration of three-dimensional reconstructions may be due to
      subtle probe movement. The ability to monitor probe movement may be helpful in
      optimizing 3D data sets.

PMID- 8736010
TI  - Influence of aging on left atrial appendage flow velocity patterns in normal
      subjects.
AB  - Transesophageal pulsed Doppler echocardiography was performed to examine changes
      with age in the left atrial appendage flow velocity patterns in 50 normal
      subjects (15 to 80 years) in sinus rhythm. There was a significant negative
      correlation between the peak early diastolic forward and backward left atrial
      appendage flow velocities and age, as well as a significant positive correlation
      between the peak early diastolic forward left atrial appendage flow velocity and
      the peak early diastolic transmitral and pulmonary venous flow velocities.
      Although there was a significant positive correlation between the peak atrial
      systolic transmitral flow velocity and age, there was a negative correlation
      between the peak atrial systolic forward and backward left atrial appendage flow
      velocities and age. There was a positive correlation between both the maximum
      left atrial diameter and the amplitude of the interatrial septal motion during
      atrial systole and age. There was a significant negative correlation between the
      left atrial appendage ejection fraction during atrial systole and age. Left
      atrial appendage thrombi and spontaneous echo contrast were detected in two
      subjects with low peak early diastolic and atrial systolic left atrial appendage
      flow velocities. In conclusion, both peak early diastolic and atrial systolic
      left atrial appendage flow velocities decreased with age. A decrease in the peak
      atrial systolic flow velocity appeared to be an important sign of left atrial
      appendage thrombus formation even in normal elderly subjects in sinus rhythm.

PMID- 8736011
TI  - The normal pattern of pulmonary venous flow on pulsed Doppler examination of the
      human fetus.
AB  - The pattern of pulmonary venous flow was studied in 52 normal fetuses between 16
      weeks gestation and term. A characteristic flow profile was defined. This was
      similar to that described in the child and adult and different from the pattern
      of flow in the systemic veins described in the fetus. The velocity of flow
      increased with gestation and was not influenced by heart rate. The velocity-time
      integral showed that systolic flow was 2.0 +/- 0.3 times the flow in diastole.
      Pulsed Doppler echocardiography demonstrates a distinctive pattern of pulmonary
      venous blood flow that reflects left atrial hemodynamics.

PMID- 8736012
TI  - An echocardiographic approach to the assessment of aortic stenosis.
AB  - An accurate echocardiographic assessment of aortic stenosis is critical for the
      cost-effective diagnosis and management of patients with the clinical suspicion
      of this diagnosis. Although the concepts involved in the echocardiographic
      determination of aortic pressure gradients and valve areas are relatively simple,
      acquisition of the data required to perform these calculations can at times be
      technically challenging. After reviewing the clinical signs and symptoms and the
      hemodynamics of aortic stenosis, this article reviews in detail the technical
      aspects involved in obtaining accurate gradients and valve areas emphasizing
      potential pitfalls.

PMID- 8736013
TI  - Flow dependence of the aortic valve area in patients with aortic stenosis:
      assessment by application of the continuity equation.
AB  - It has been argued that the aortic valve area (AVA) in patients with aortic
      stenosis increases with flow. Others, however, have attributed the apparent
      increase to flow dependence of the empiric constant in the Gorlin formula. We
      examined the changes in AVA during changes in transvalvular flow induced by
      dipyridamole infusion in 34 patients with aortic stenosis. Two-dimensional and
      Doppler echocardiography was used and AVA was calculated according to the
      continuity equation, which does not include empiric constants. Flow increased in
      29, decreased in four, and was unchanged in one patient. There was a linear
      correlation between percent change in flow and percent change in AVA: delta AVA%
      = 1.1 + delta flow%. 0.56 (r = 0.72; p < 0.001) In conclusion, AVA was found to
      be flow dependent. The magnitude of change in AVA observed by noninvasive
      recordings agrees with previous invasive studies according to the Gorlin formula.

PMID- 8736014
TI  - Double-chambered right ventricle: echocardiographic features.
AB  - Double-chambered right ventricle is an uncommon congenital heart disease, studied
      mostly by angiography, characterized by the division of the right ventricular
      cavity into two different pressure chambers. To analyze the anatomic features of
      this disease, data from 13 patients examined by echocardiography at the Mayo
      Clinic were reviewed. Despite the anatomic variety of this abnormality, two main
      types were identified. In the first type, intraventricular obstruction was due to
      an anomalous muscle bundle crossing the right ventricular cavity from the
      interventricular septum to the parietal wall. In the second type, no anomalous
      bundles were identified, and interventricular obstruction was due to marked
      parietal and septal hypertrophy. The main interventricular gradient was higher in
      the first type, and a ventricular septal defect was found to be associated more
      commonly with the second type.

PMID- 8736015
TI  - The clinical value of blunting of cyclic gray level variation for the detection
      of acute cardiac rejection: a two-dimensional, Doppler, and videodensitometric
      ultrasound study.
AB  - Aims of this study were to assess (1) whether videodensitometric analysis of
      myocardial gray-level variation can distinguish normal from rejecting
      transplanted hearts in a clinical setting and (2) whether this sign, used in
      combination with the other conventional two-dimensional and Doppler
      echocardiographic findings, might improve the accuracy of ultrasound techniques.
      Thirty heart transplant recipients (23 men; mean age 40 years; range 20 to 54
      years) were studied in 87 different situations by endomyocardial biopsy and
      echocardiographic evaluation. Of the 87 situations, 37 ("rejectors") showed
      histologic evidence of rejection of mild (n = 17) or moderate (n = 10) severity
      and 50 ("nonrejectors") did not show rejection processes. Cyclic variation was
      decreased significantly in rejectors compared with nonrejectors in both the
      septum (15% +/- 10% versus 25% +/- 11%; p < 0.0001) and the posterior wall (19%
      +/- 10% versus 25% +/- 12%; p < 0.01). When a cutoff of 20% or greater of cyclic
      variation in the septal wall was taken as a positivity criterion, it yielded a
      70% sensitivity and 70% specificity for identifying rejection. Sensitivity of
      conventional two-dimensional and Doppler echocardiographic signs was 51% and
      increased to 89%, increased by the videodensitometric criteria (p < 0.001).
      Specificity was 92% and decreased to 62% with videodensitometric criteria (p <
      0.001). Overall diagnostic accuracy was 75% for conventional two-dimensional
      echocardiographic Doppler criteria alone and remained unchanged by the addition
      of videodensitometric criteria. In conclusion, blunting of cyclic gray-level
      variation induced by rejection is detectable with videodensitometric analysis.
      The clinical impact of this sign appears to be limited, because the resulting
      increase in sensitivity is counter-balanced by a reduced specificity compared
      with the currently available conventional ultrasound techniques.

PMID- 8736016
TI  - Diagnostic performance of myocardial contrast echocardiography for detection of
      stunned myocardium.
AB  - Improvement in regional wall motion after acute myocardial infarction has been
      described up to 2 to 3 weeks after the acute event despite restoration of blood
      flow by early successful reperfusion therapy. The prospective identification of
      potentially reversible ventricular dysfunction caused by stunned myocardium has
      significant clinical implications. Twenty-seven patients with acute myocardial
      infarction underwent myocardial contrast echocardiography (MCE) before,
      immediately after, and 4 weeks after successful reperfusion therapy. MCE was
      performed by imaging a parasternal short-axis view during intracoronary arterial
      injection of 2 ml sonicated ioxaglate (Hexabrix-320). The contrast defect area
      and contrast-filled area before reperfusion were defined as the risk area and
      noninfarct area, respectively. The normalized gray level was defined as the ratio
      of the gray level in the risk area/gray level in the noninfarct area. In 21
      patients, wall motion was akinetic or dyskinetic immediately after reperfusion,
      and 10 of 21 patients in whom wall motion recovered during the chronic stage were
      defined as patients with stunned myocardium. In patients who showed asynergic
      wall motion immediately after reperfusion, MCE predicted the recovery of left
      ventricular wall motion (stunned myocardium) during the chronic stage with a
      sensitivity of 77%, specificity of 100%, and predictive accuracy of 86%, when a
      normalized gray level of more than 0.4 was presumed to predict stunned
      myocardium. We conclude that MCE provided the prospective identification of
      potentially reversible ventricular dysfunction caused by stunned myocardium, and
      wall motion in the area of nonenhanced myocardium on MCE immediately after
      reperfusion is not expected to show reversible dysfunction.

PMID- 8736017
TI  - Interobserver and intraobserver variation for analysis of left ventricular wall
      motion at baseline and during low- and high-dose dobutamine stress
      echocardiography in patients with high prevalence of wall motion abnormalities at
      rest.
AB  - Interobserver and intraobserver variation for analysis of left ventricular
      regional wall motion during dobutamine stress echocardiography was assessed.
      Computer-displayed cineloops from 33 patients, 25 with baseline wall motion
      abnormalities, were analyzed by two observers blinded for patient data.
      Assessment included (1) baseline wall motion abnormalities, (2) evidence of
      myocardial viability at 10 micrograms/kg/min dobutamine, and (3) evidence of
      myocardial ischemia at 30 to 40 micrograms/kg/min. Wall motion score index was
      calculated at each stage. Interobserver and intraobserver agreement for baseline
      wall motion abnormalities was 100%. Interobserver agreement for viability and
      ischemia was 84% and 82%, respectively; intraobserver agreement was 92% and 85%,
      respectively. Mean interobserver differences in wall motion score index ranged
      from 0.06 +/- 0.14 at baseline to 0.09 +/- 0.20 at high doses (p < 0.05 at all
      levels); mean intraobserver differences ranged from 0.001 +/- 0.14 to 0.01 +/-
      0.15 (difference not significant at all levels).

PMID- 8736018
TI  - Determinants of echodensity at the intima-media interface with intracoronary
      ultrasound imaging.
AB  - A thin, echodense layer (EL) is sometimes observed at the intima-media interface
      on intravascular ultrasonographic images. We reviewed a series of 119
      histologically matched, 30 MHz, in vitro ultrasound cross sections of human
      coronary arteries for factors determining the occurrence of an EL. ELs were
      observed in 19 (27%) of 71 images with optimal gain settings, in two (17%) of 12
      with high gain settings, and in none of 26 with low gain settings. In 17 (94%) of
      18 cross sections with eccentric catheter positions, an EL was visible only in
      parts of the vessel wall that were perpendicular to the ultrasound beam. ELs were
      seen behind fibrous, lipid-rich, and mixed lesions but not behind calcified
      lesions because of acoustic shadowing. The presence or morphologic elements of
      the internal elastic lamina did not influence the occurrence of an EL. We
      conclude that the occurrence of an EL at the intima-media interface depends on
      acoustic factors and gain settings, and it provides no anatomic information per
      se.

PMID- 8736019
TI  - Echocardiographic demonstration of coronary sinus diverticula in patients with
      Wolff-Parkinson-White syndrome.
AB  - Coronary sinus (CS) diverticula have been reported to be the anatomic basis of
      some posteroseptal accessory atrioventricular pathways. During 1 year, 53
      patients with Wolff-Parkinson-White syndrome referred to our center for catheter
      ablation were found to have posteroseptal or left posterior accessory pathways.
      The accessory pathway was associated with an anomaly of the CS in seven patients
      (13%), including six diverticula of the CS or its branches and one aneurysmal CS.
      Four of the CS diverticula were visualized by transesophageal echocardiography.
      Diverticular appear as echolucent, contractile pouches on the epicardial surface
      of the posteroseptal or posterior left ventricle that connect to the CS by an
      isthmus. Previous reports have suggested that accessory pathways associated with
      CS aneurysms have rapid conduction times and may be associated with an increased
      risk of rapid ventricular response during atrial fibrillation and sudden death;
      five of our seven patients had a short preexcited R-R interval in the range of
      172 to 225 msec during atrial fibrillation. In summary, many, if not the
      majority, of CS diverticula associated with preexcitation can be visualized by
      transesophageal echocardiography.

PMID- 8736020
TI  - Acute limb ischemia and heparin-induced thrombocytopenia: the value of
      echocardiography in eliminating a cardiac source of arterial emboli.
AB  - We report an unusual thromboembolic event occurring during severe heparin-induced
      thrombocytopenia. A left intraventricular thrombus was diagnosed as the source of
      multiple arterial emboli, resulting in an initial cerebrovascular event and
      subsequent bilateral acute lower extremity ischemia requiring emergency surgery.
      No underlying heart disease was detected. Pathologic examination of the
      embolectomy specimen revealed fibrin platelet aggregates with rare white and red
      blood cells, consistent with a "white thrombus." We conclude that routine
      monitoring of platelet count should be performed in all patients receiving
      heparin to identify promptly individuals who have heparin-induced
      thrombocytopenia, and when thromboembolic complications occur in this setting,
      echocardiography is indicated to identify possible intracardiac sources for
      emboli, even in patients with previously known structurally intact hearts.

PMID- 8736021
TI  - Transesophageal echocardiographic image of double-chambered right ventricle.
AB  - Double-chambered right ventricle is a rare congenital heart disease. Anomalous
      muscle bundles in the right ventricle divide the right ventricle into two
      portions and cause intracavitary obstruction of the right ventricle.
      Transesophageal echocardiography of the double-chambered right ventricle has
      never been reported. We present a 32-year-old man with double-chambered right
      ventricle associated with perimembranous-type ventricular septal defect and left
      superior vena cava. Multiplane transesophageal echocardiography provides
      excellent views of an anomalous muscle bundle in the right ventricle, which
      differed from a moderator band by its insertion site on the right ventricle.

PMID- 8736022
TI  - Echocardiographic evaluation of papillary fibroelastoma: a case report and review
      of the literature.
AB  - Papillary fibroelastomas comprise approximately 7.9% of benign primary cardiac
      tumors. Although papillary fibroelastomas were at first discovered incidentally
      at autopsy or during heart surgery, these tumors are increasingly being
      identified by echocardiography. This article reviews those papillary
      fibroelastomas detected by transthoracic or transesophageal echocardiography and
      discusses the echocardiographic features of these tumors, associated symptoms,
      and management. Echocardiography is important in influencing management decisions
      regarding excision, valve replacement, and valve repair.

PMID- 8736023
TI  - Resorbable polyesters in cartilage engineering: affinity and biocompatibility of
      polymer fiber structures to chondrocytes.
AB  - The resorbable polymers polyglycolic acid (PGA) and polylactic acid (PLA) are
      gaining increasing importance in tissue engineering and cell transplantation. The
      present investigation was focused on the biocompatibility and cell retaining
      behavior of PGA/poly-L-lactide (PLLA) (90/10) and PLLA nonwoven structures for
      the in vitro development of chondrocyte-polymer constructs. The effect of the
      relevant monomers to chondrocytes was analyzed. Type II collagen and poly-L
      lysine were compared to improve loading of PGA/PLLA and PLLA polymer nonwovens
      with chondrocytes. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zoliumbrom
      ide (MTT) test was applied for quantification. At concentrations above 2 mg/mL,
      glycolic acid was more cytotoxic than lactic acid. As shown by pH equilibration,
      the cytotoxic effect is not due merely to the acidity of the alpha-hydroxy acids.
      Regarding the degradation products, glycolic acid, and L(+) lactic acid,
      nonwovens of PLLA are more biocompatible with chondrocytes than nonwovens of
      polyglycolide. Collagen type II and poly-L-lysine generally improved cell seeding
      on resorbable polymers in tissue engineering; however, their efficiency varies
      depending on the type of fiber structure.

PMID- 8736024
TI  - Shape and size of virgin ultrahigh molecular weight GUR 4150 HP polyethylene
      powder.
AB  - Sizes and shapes of micron- and submicron-sized structures in four lots of virgin
      GUR 4150 HP ultrahigh molecular weight polyethylene powder were determined by
      using low-voltage scanning electron microscopy and image analysis. One thousand
      two hundred micron-sized virgin powder particles and 1200 of their constituent
      submicron-sized structures were analyzed. The mean maximum diameter of the micron
      sized particles was 81.3 microns, and that of the submicron-sized particles was
      0.82 micron. Particle shapes, as determined by the aspect ratio (maximum diameter
      divided by minimum diameter), were remarkably consistent from lot to lot and
      between micron- and submicron-sized particles (1.55 versus 1.53, respectively).
      Significant lot to lot variability was observed in the sizes of the micron-sized
      particles, and the size distribution of the submicron-sized particles closely
      follows the size distribution of the submicron-sized particles observed in tissue
      retrievals. This variability leads to questions about variability in polyethylene
      quality and in vivo wear performance. Size similarity between the submicron-sized
      particles retrieved from tissues and that observed in virgin powder supports the
      hypothesis that polyethylene debris has two origins: particles released from
      structures retained from the virgin powder, and particles generated de novo by
      friction and wear.

PMID- 8736025
TI  - A differential scanning calorimetry study of retrieved orthopedic implants made
      of ultrahigh molecular weight polyethylene.
AB  - Differential scanning calorimetry (DSC) was used to examine thermal and
      thermooxidative properties of ultrahigh molecular weight polyethylene (UHMW-PE)
      of five acetabular components of failed orthopedic implants retrieved at revision
      of total hip arthoplasty. The results were compared with controls (unimplanted
      acetabular cups, a 20-year-old slab of UHMW-PE, and raw material). Profiles of
      exothermic peaks indicated increased levels of oxidation in all retrieved cups.
      In three retrieved cups, DSC revealed an additional peak of endotherm that was
      not seen in control samples. The additional endotherm peaks were not artifacts
      due to oxidation during scanning, heat buildup during cutting of the samples, or
      the sterilization method after retrieval. The additional peak was associated with
      the bulk of the polymer that was extracted with hexane. It varied in relative
      area, depending on its original location of the sample in a cup, implicating
      local variability in the extent of changes in material property. The distribution
      of the changes suggests that, during implantation, tissue exposure and friction
      affected the level of oxidation and degree of crystallinity in the UHMW-PE to a
      greater degree than did loading alone. Overall results showed that DSC may be a
      useful tool in evaluating changes in the properties of UHMW-PE orthopedic
      components in vivo.

PMID- 8736026
TI  - Calorimetric characterization of the formation of acrylic type bone cements.
AB  - The formation of acrylic bone cements upon heating was investigated by
      differential scanning calorimetry (DSC). The effects of the contents of
      initiators, accelerator, biocompatibilizer, and crosslinking agents on the rate
      and the heat of polymerization during DSC heating were studied. The rate and the
      heat of polymerization (delta H) were characterized by the peak temperature and
      the area of the DSC exotherm, respectively. It was found that both the rate and
      heat of polymerization decreased with increasing heating rate. The delta H was
      increased considerably with increasing benzoyl peroxide (BPO) initiator
      concentration from 1 to 10% (w/v), whereas the rate of polymerization was reduced
      significantly. An increase in azobisisobutyronitrile (AIBN) initiator
      concentration also induced an increase in delta H, but the rate of reaction was
      not affected considerably. The addition of accelerator promoted the rate of
      reaction but resulted in a drop in delta H. The rate of polymerization for the
      system containing BPO initiator was increased quite significantly with the
      addition of hydroxyethyl methacrylate (HEMA) biocompatibilizer, while the delta H
      was slightly increased. For the system using AIBN as the initiator, the rate of
      polymerization was decreased slightly and the delta H dropped significantly with
      the addition of HEMA. The effect of ethylene glycol dimethacrylate (EGDMA)
      crosslinking agent was also examined. Polymerization became more rapid with the
      addition of EGDMA in the bone cement using BPO initiator, while it remained
      approximately constant for the system using AIBN as the initiator. No systematic
      change in delta H was observed with the addition of EGDMA in both systems. This
      study demonstrated that DSC is a potential tool to measure the amount of heat
      released and also the rate of polymerization for bone cements.

PMID- 8736027
TI  - Characterization of experimental composite biomaterials.
AB  - A comparison was made among the elastic moduli of various combinations of
      dimethacrylates that may be used as matrix resins in dental restorative composite
      biomaterials systems. Two ceramic filler materials with contrasting shape and
      size were synthesized by wet chemistry; these were used to produce a range of
      experimental composite systems. Dynamic elastic moduli determinations were used
      to study the influence of filler volume, filler size/shape, use of silane
      coupling agents, and storage in water. The filler was varied from 0 to 59% by
      volume for filler A and from 0 to 48% volume for filler B. Silane treatment was
      found to have a significant effect on modulus. Moduli for composite materials
      containing silane-treated filler were higher compared to materials containing the
      same volume loading of non-silane-treated filler. Using a light curing resin as a
      matrix gave a significantly higher modulus for a filler loading of 38% by volume.
      Storage in water for 29 days was found to have only a slight effect on moduli for
      composite systems containing in excess of 20% by volume of filler. The
      experimental composite systems produced slightly higher values for moduli than
      were predicted by the theoretical Reuse constant stress model.

PMID- 8736028
TI  - Glutaraldehyde retains its disinfectant properties in presence of
      hydroxypropylmethyl cellulose (HPMC) gel.
AB  - Explanted medical devices are routinely sent to laboratories at the Center for
      Devices and Radiological Health for analysis. The shipping of these devices
      presents potential hazards to personnel as well as an opportunity for damage to
      the devices. In an effort to address these concerns, a viscous disinfecting
      shipping medium that would limit splashing and cushion a suspended device was
      proposed. Consequently, we investigated the disinfectant properties of adding a
      gelling agent, hydroxypropylmethyl cellulose (HPMC) to common disinfectants. We
      found that the germicidal effectiveness of 2.5% glutaraldehyde in 0.05 M borax
      when tested against Bacillus subtilis spores was not changed by the addition of
      2% HPMC. In addition, HPMC appears to be compatible with 70% ethanol and at least
      one commercial disinfectant containing a quaternary ammonium compound.
      Preliminary experiments indicate that an HPMC-disinfectant gel is a potentially
      useful packaging agent for minimizing the hazards to personnel and materials
      during shipping of explanted medical devices. The use of such a medium would be
      subject to guidelines within the context of a program for handling biologically
      contaminated materials.

PMID- 8736029
TI  - A bibliography of monographic works on biomaterials and biocompatibility: update.

PMID- 8736030
TI  - Is there any difference between vacuum mixing systems in reducing bone cement
      porosity?
AB  - Six vacuum mixing systems, Cemvac, Merck, Mitvac, Optivac, Osteobond, and
      Stryker, were tested using prechilled Palacos R bone cement to investigate the
      reduction of porosity compared to mixing at atmospheric pressure. In addition the
      Optivac, Osteobond, and Stryker were tested using Simplex P bone cement to find
      out if they were effective in reducing the porosity of a middle viscosity bone
      cement. All vacuum mixing systems reduced the number of macropores (> 1 mm) and
      micropores (0.1 mm < voids < 1 mm) and increased the density of both Palacos R
      and Simplex P. But only the Optivac, Stryker, and Merck systems reduced the area
      percentage of macropores with more than 50% compared to the control. When using
      Simplex P bone cement, all three mixing systems tested reduced the numbers and
      the area percentage of macropores compared to the control. The results show that
      vacuum mixing is effective in reducing the porosity in both a high viscosity
      cement such as Palacos R and a middle viscosity cement such as Simplex P. Not all
      systems tested were effective in reducing the number and size of large voids.

PMID- 8736031
TI  - The involvement of serotonin (5-hydroxytryptamine) in photosensitive epilepsy.
AB  - Over the last decade, vigorous efforts have been made by neuroscientists to
      unravel the cellular and molecular basis of photosensitive Epileptogenic
      activities in the central nervous system (CNS). Many neurotransmitters are
      implicated in brain activities but the extent to which they participate in these
      activities needs to be clarified. This review discusses the involvement of
      serotonin (5-hydroxytryptamine, 5-HT) in photosensitive epilepsy. The
      biosynthesis, metabolism, and structural and functional distribution of serotonin
      in the brain, and the role of 5-HT, its precursors, metabolites, receptors,
      agonists, antagonists, and the enzymes of reaction in photosensitive
      epileptogenic activity with reference to 5-HT cortical density, are discussed.
      The effects of biosynthetic and metabolic impairments in the serotonergic system,
      and the extent to which they contribute to the elicitation of myoclonic
      phenomena, hallucination, impulsivity, and migraine (HIMM) in photosensitive
      epilepsy are critically reviewed, and supported by evidence from animal models of
      photosensitive epilepsy. This evidence is correlated with the clinical findings
      in human photosensitive epilepsy.

PMID- 8736032
TI  - Power equation for all-or-none effects of oxygen toxicity and cumulative oxygen
      toxicity.
AB  - Quantification of the level of O2 toxicity may provide a means of setting limits
      on various hyperoxic exposures. A previously suggested expression for
      quantitative oxygen toxicity, DMG = a x t2 x PO2c (t-time, DMG-measured level of
      O2 toxicity), has been adapted for the all-or-none phenomenon: K = t2 x PO2c. A
      symptom may appear when K reaches a threshold value Kc. Non-linear regression was
      successfully applied to all-or-none symptoms from the literature: survival,
      convulsions, substernal distress, reduction in short circuit current and nerve
      conduction blockade. The generality of these expressions enabled calculation of
      cumulative oxygen toxicity and a search for the mechanism of oxygen toxicity.
      Cumulative oxygen toxicity is calculated in three-step calculation loops in three
      suggested exposure profiles. For a possible recovery period between exposures the
      expressions took the form: DMGt = DMGc x e-rt, and Kt = Kc x e-rt, where r is the
      recovery constant. A possibly bimodal distribution of c close to the values of 1
      and 4 could be attributed to systemic effects.

PMID- 8736033
TI  - Dual effect of aminophylline on the ventilatory response to hypoxia in the rat.
AB  - Male Hooded Wistar rats were exposed to three five-minute periods of hypoxia in
      which they breathed a gas mixture comprising 7% O2 and 93% N2. Before the second
      and third hypoxic exposures rats were injected (i.m.) with aminophylline (an
      adenosine antagonist) at a dose of 15 mg.kg-1. In control animals, hypoxia caused
      an increase in ventilation which was greater during the first than during the
      fifth minute of hypoxia. Each injection of aminophylline significantly increased
      ventilation in air-breathing rats. However, the first dose of the drug did not
      significantly alter the hypoxic ventilatory response. The second dose of
      aminophylline had two effects on ventilation during hypoxia. It reduced the
      ventilatory response during the first minute of hypoxia, and also prevented the
      fall in ventilation between the first and fifth minute of exposure.
      Ethylenediamine injections had no effect on ventilation or the responses to
      hypoxia. The results suggest that adenosine has a dual role in respiratory
      control during hypoxia, one excitatory and the other inhibitory. Although
      previous studies have already identified such roles for adenosine, the present
      study may represent the first time in which these have been demonstrated in a
      single animal model.

PMID- 8736034
TI  - Effect of CO2 on Vth nerve inhibition of respiration in isolated rat nervous
      system.
AB  - The role of hypercapnia in terminating trigeminal (Vth) nerve inhibition of
      respiration is not clear. Phrenic nerve responses to Vth nerve stimulation were
      examined during eucapnia and hypercapnia. We hypothesized that hypercapnic
      stimulation might not be sufficient to overcome the inhibitory effects of the Vth
      nerve, and thus would fail to restore respiratory center output to baseline
      values. Isolated rat brainstem-spinal cord preparations from newborn rats were
      placed in a tissue bath and superfused with modified Krebs solution at 27 degrees
      C. Respiratory related activity was recorded from cut C1 or C5 ventral roots.
      Tonic stimulation of the Vth nerve (1 Hz for 15 min) under eucapnic conditions
      initially inhibited the frequency of respiratory activity over the first 1-2 min,
      followed by partial recovery after 4 min to 50-60% of the control level.
      Stimulation of the Vth nerve at 0.5 Hz initially decreased the respiratory
      frequency to about 40% of baseline over the first 3 min, which then increased to
      control levels within 6 min despite continued Vth nerve stimulation. Exposure to
      hypercapnia (15 KPa PCO2) increased the baseline respiratory frequency. However,
      hypercapnic stimulation only partially reduced the degree of the Vth nerve
      inhibitory effect. We conclude that 15 KPa PCO2 only partially reverses the
      inhibitory effect of the Vth nerve stimulation at the level of the central
      respiratory controller.

PMID- 8736035
TI  - Mechanisms of circulatory depression during simulated central apneas in the
      anesthetized dog.
AB  - We recently reported that during simulated central apneas (SCA) heart frequency
      was more severely depressed than during obstructive apneas. In the present study,
      we examined factors influencing this response including hypoxia, hypercapnia,
      mechanoreceptor input and the role of the vagus nerve. In 11 paralyzed and
      mechanically ventilated animals, SCA was produced by turning the ventilator off
      for 1 min and on for 1 min. This was done with and without hypoxia, before and
      after bilateral cervical vagotomy. We also compared the effects of SCA with
      matched intermittent hypoxia. Under all conditions during room air breathing
      arterial pO2 fell and pCO2 rose to approximately the same values: 49 and 57 torr,
      respectively. Compared with baseline, during SCA following room air breathing
      blood pressure and cardiac output did not change significantly, and heart
      frequency decreased by 47% (p<0.001). Following 100% O2 breathing, during SCA
      mean blood pressure did not change, cardiac output decreased by 20% (p<0.05) and
      heart frequency decreased by 27% (p<0.02), a decrease which was significantly
      less than that following room air breathing (p<0.02). Immediately upon resuming
      ventilation, on room air, heart frequency increased by 15 bpm (p<0.02); heart
      frequency did not increase post-apnea an 100% O2. After vagotomy, following room
      air breathing, blood pressure increased during apnea by 32% (p<0.001) and heart
      frequency decreased by only 10% (p<0.05). Oxygen breathing prevented the increase
      in blood pressure during apnea but heart frequency was still reduced by 16%
      (p<0.05). During intermittent hypoxia matched for periodicity and pO2 to SCA,
      there were no changes in heart frequency. We conclude that the cardiovascular
      response to apnea is more than just that to intermittent hypoxia, and is
      critically dependent on loss of respiratory mechanoreceptor afferent input,
      hypercapnia, and an intact vagus nerve. Blood pressure responses are also
      dependent on the vagus nerve.

PMID- 8736036
TI  - Power spectrum analysis of spontaneous fluctuations in the photoplethysmographic
      signal.
AB  - Direct measurement of variability in the peripheral circulation was performed by
      means of photoplethysmography, which provides assessment of blood volume in
      tissue and systolic blood volume increase. Both parameters showed oscillations at
      a relatively low frequency, about 0.02 Hz, and a relatively high frequency, about
      0.3 Hz, which is related to respiration. These frequencies are similar to those
      found in measurements of heart rate variability--which is also obtained by
      measuring the photoplethysmographic period variability--but the powers of the
      different frequencies are different. The low frequency oscillation, which is
      attributed to the activity of the sympathetic nervous system, is more pronounced
      in the measurements of tissue blood volume and of systolic blood volume increase
      than in the measurement of heart rate.

PMID- 8736037
TI  - The effect of hypothermia on gas exchange in anaesthetized rats in a confined
      atmosphere.
AB  - Both hypothermia and anaesthesia are known to prolong hypoxic survival. The
      combined effect of anaesthesia and hypothermia on survival in a confined
      atmosphere was studied in rats whose O2 consumption (VO2) produced hypoxia. Blood
      gases and respiratory parameters were measured in either ambient temperature TA =
      30 degrees C (final body temperature TB = 36 degrees C) or initial TA = 30
      degrees C followed by TA = 0 degree C below 100 torr inspired O2 (final TB = 19
      degrees C). Oxygen consumption, breathing frequency and heart frequency decreased
      in hypoxic hypothermia compared to hypoxic normothermia. Hypothermia did not
      affect blood pressure, blood gas tension of pH. Hypothermia in hypoxia: 1)
      reduced the demand for oxygen with respect to O2 transport; 2) abolished the
      normothermic elevation of lactate in the blood, and 3) maintained high arterial
      saturation of oxygen. In contrast with awake rats (our previous study), there was
      no difference in the terminal inspired PO2 and survival time for normothermia and
      hypothermia in the anaesthetized rat, but survival time was doubled by
      anaesthesia as compared to awake rats due to reduced VO2.

PMID- 8736038
TI  - Pentoxifylline-induced vasodilatation is not endothelium-dependent in rabbit
      aorta.
AB  - It is well known that phosphodiesterase inhibitors, such as MB 22948 or
      papaverine, induce endothelium-dependent relaxation by potentiating the effects
      of endothelium-derived relaxing factor released spontaneously in vascular
      tissues. The present study was planned to determine whether the vasodilator
      properties of pentoxifylline, a phosphodiesterase inhibitor, are endothelium
      dependent and modulated by its phosphodiesterase inhibitory activity in rabbit
      aorta. In opened aortic rings precontracted with phenylephrine (0.5 microM),
      pentoxifylline (1 microM-1 microM) caused concentration-dependent relaxation.
      Pentoxifyl line-induced relaxation was not modified by incubation with methylene
      blue (10 microM) or NG-nitro-L-arginine methyl ester (0.1 microM), or by
      mechanical denudation of endothelium. Forskolin (1nM-0. 1mM) and sodium
      nitroprusside (10nM-0. 1mM) induced concentration-dependent relaxations in both
      endothelium containing and endothelium denuded preparations. The relaxation
      induced by forskolin and sodium nitroprusside, which are cyclic AMP and cyclic
      GMP mediated, respectively, and which are both endothelium-independent, were not
      altered after incubation with pentoxifylline (0.1 mM) for 30 min. In conclusion,
      our experiments suggest that the vasodilator properties of pentoxifylline in
      isolated rabbit aorta are primarily at the level of the vascular smooth muscle
      and may not involve EDRF or its phosphodiesterase inhibitory activity.

PMID- 8736039
TI  - Cadmium induced lipid peroxidation in kidney function.
AB  - Since the kidney is the main target organ for many metals including cadmium, the
      generation of the products of lipid peroxidation due to accumulation of these
      toxic metals in the kidney may have importance in the mechanism of their
      nephrotoxicity. In order to test this hypothesis, we carried out an experimental
      study in rats. The functions and the levels of tiobarbituric acid reactive
      substances (TBARS) of the kidney were investigated in animals receiving 15
      micrograms/ml aqueous Cd solution for 30 days. Due to cadmium accumulation in
      kidney cortex, the ratio of Cd/Zn increased significantly and this increase was
      associated with elevated TBARS in both renal cortex and medulla. The content of
      TBARS in renal cortex rose from 211.6 +/- 64.2 to 303.4 +/- 46.4 nmol/g protein
      (p<0.01) and GFR decreased to 390.5 +/- 109.4 from 1008.7 +/- 4.8 microliters/min
      (p<0.01) in cadmium exposed animals. Daily coadministration of selenium, vitamins
      A, C, E did not reverse the adverse effect of cadmium on kidney function, despite
      the significant decrease in cortex TBARS levels (p<0.01). In conclusion, these
      data suggest to us that lipid peroxidation assessed by TBA test may not be the
      only mechanism in cadmium induced nephrotoxicity.

PMID- 8736040
TI  - Paroxysmal atrial fibrillation and stroke (cerebrovascular accidents) in males
      and females above and below age 65 on days of different geomagnetic activity
      levels.
AB  - The goal of this study was to determine whether differences exist in the
      frequency of paroxysmal atrial fibrillation and stroke (cerebrovascular accident)
      on days of different geomagnetic activity levels. Geomagnetic activity was
      divided into four levels: quiet (I degree), unsettled (II degree), active (III
      degree), and stormy (IV degree). Measurements were made according to the six
      highest hourly geomagnetic parameters, in nanotesla units, over 24 hours. The
      study period covered 1185 consecutive days, from January 1990 to March 1993. All
      patients treated in the Admissions Department of a major multiprofile university
      hospital for stroke (cerebrovascular accident) (977 patients) or paroxysmal
      atrial fibrillation (653 patients) were included. Groups were also divided by sex
      and age (< or = 65 years vs. > 65 years) for comparison. RESULTS: (1) There was a
      significant negative correlation between daily paroxysmal atrial fibrillation and
      geomagnetic activity level (r = 0.976, p = 0.02); (2) The absolute number of
      daily admission for paroxysmal atrial fibrillation was higher on geomagnetic
      activity I degree days than on IV degree days (p < 0.004); (3) Stroke showed the
      same negative correlation with geomagnetic activity as paroxysmal atrial
      fibrillation, but only in males 65 years of age or less (r = 0.976, p = 0.027)
      suggesting a predominantly arrhythmic origin of stroke (cerebrovascular accident)
      in this group; (4) The male/female ratio for stroke was also adversely correlated
      with geomagnetic activity (r = 0.99, p = 0.0008), with the highest absolute
      number occurring on geomagnetic activity I degree days (X2 = 4.538, p = 0.03).
      These data are in accordance with previous studies showing increased heart
      electrical instability during periods of lowest geomagnetic activity.

PMID- 8736041
TI  - Cause of catecholamine distribution change in the schizophrenic brain.
AB  - The existence of an additional or augmented (in comparison with the norm) inner
      source of electrical stimulation of the reward system (hypothalamic in
      particular) is discussed as a possible cause for catecholamine distribution
      change in the schizophrenic brain. Our previously described model of behavioral
      disorders was based on this idea and several important conclusions were deduced
      from it, including the theory of illusion formation in norm versus pathology. The
      unexpected possibility of applying the same model to the problem of
      catecholamines in the schizophrenic brain indicates a path towards a unified
      theory of schizophrenia.

PMID- 8736042
TI  - Inhibition of LDL-associated phospholipase A activity in human plasma by albumin.
AB  - LDL has been previously shown to exhibit activity of phospholipase A1 and
      phospholipase A2 as measured by the hydrolysis of NBD caproic phosphatidylcholine
      (C6-NBD-PC), which is considered to represent the phospholipase activity towards
      short chain or oxidized fatty acyl chains/3/. In the present study we show that
      in whole plasma the LDL-associated phospholipase A activity, measured by the
      hydrolysis of C6-NBD-PC, is inhibited by albumin due to its binding of the
      substrate. The inhibition depends on the molar ratio between the substrate,
      albumin and the enzyme. C6-NBD-PC and other synthetic phospholipid analogues have
      been used previously to determine plasma phospholipase A2 activity in various
      pathological states. This study suggests that when using this kind of substrate
      to measure plasma PLA activity, the choice of substrate and the experimental
      conditions should be carefully considered. Determination of the appropriate ratio
      between the three reaction components--enzyme, substrate and albumin--is required
      for reliable and consistent determination of plasma phospholipase activity.

PMID- 8736043
TI  - Time dependency of pyridostigmine-induced growth hormone response.
AB  - Growth hormone (GH) plasma levels reflect a balance between stimulation via GH
      releasing hormone (GHRH) and inhibition by somatostatin (SS). Steroids influence
      GH secretion by modulating SS tone. There is a correlation between the diurnal
      secretion of GH and cortisol (CORT). Pyridostigmine, the acetylcholinesterase
      inhibitor, increases cholinergic tone, inhibits SS release and increases the
      release of GH. We investigated the influence of CORT on pyridostigmine-induced GH
      responses by testing subjects at 9.00 and 14.00 h. Basal (mean +/- SEM) CORT
      levels at 9.00 and 14.00 h were 251.5 +/- 18.4 nmol/l and 142.7 +/- 6.7 nmol/l,
      respectively. Pyridostigmine-induced GH responses were greater at 9.00 h than at
      14.00 h (8.7 +/- 1.5 mU/l; 3.0 +/- 1.0 mU/l, respectively, [ p < 0.001]). A
      positive correlation between CORT and delta GH values was demonstrated (p <
      0.0004).

PMID- 8736044
TI  - Has nicotine a local anaesthetic action?
AB  - In this study, we investigated whether nicotine may have a local anaesthetic
      action in mice, using the tail press and tail immersion tests. Nicotine increased
      the latent time of biting the clip in the tail press test (p < 0.001) and
      retarded tail withdrawal latency in the tail immersion test (p < 0.01), compared
      to controls. These results suggest that nicotine may possess a local anaesthetic
      action.

PMID- 8736045
TI  - The effect of quinidine and myocardial ischemia on the isolated rat heart with
      fat-free diet.
AB  - Fat-free diet changes the lipid content and the electrophysiological properties
      of the rat myocardium. Five percent fat supplementation to the diet does not
      alter the basic electrophysiological properties but still has a biochemical
      effect on the lipid content of the myocardium. The purpose of this work was to
      determine whether these biochemical alterations affect the response of the
      myocardium to quinidine and ischemia, both of which interact with the lipid
      component of the membrane. We used strength-duration, strength-interval and
      threshold of ventricular fibrillation to measure the electrophysiological
      properties of the isolated rat heart at baseline and after 30 minutes of
      quinidine perfusion or coronary artery ligation. The fatty acid composition of
      the myocardium was analyzed. We found that a fat-free diet caused essential fatty
      acid deficiency, while 5% fat supplementation had a partial protective effect.
      Quinidine decreased excitability and increased refractoriness in both groups but
      had more effect on the fat-free diet hearts group. There was no difference in the
      ventricular fibrillation threshold. Ischemia increased myocardial excitability in
      the fat-free diet hearts group and had no effect on refractoriness or ventricular
      fibrillation threshold. These results support the theory that the lipid
      composition of the myocardial membrane affects its response to lipophilic drugs
      and ischemia.

PMID- 8736046
TI  - The effects of physostigmine, L-arginine and NG-nitro-L-arginine methyl ester (L
      NAME) on the mean arterial pressure of the rat.
AB  - The effects of physostigmine, L-arginine and NG-nitro-L-arginine methyl ester (L
      NAME) were investigated in urethane-anaesthetized rats. The drugs were chosen
      because physostigmine has been known to produce an increase in peripheral
      adrenergic activity, whereas L-arginine and L-NAME have been known to modulate
      nitric oxide (NO) production. Slow infusion of L-arginine produced significant
      hypotension, but only in animals pretreated by physostigmine. L-NAME applied in
      the same way produced a slow developing increase in blood pressure, but not in
      animals pretreated by physostigmine. The pressor responses to physostigmine were
      potentiated if the drug was injected during infusion of L-NAME, and depressed if
      the drug was injected after stopping L-NAME infusion (in rats not pretreated with
      physostigmine). It is concluded that L-arginine-NO pathways act in vivo to oppose
      peripheral vasoconstrictor influences coupled with central cholinergically
      mediated activation of the adrenergic system, as produced by physostigmine. In
      this way, NO is part of a general mechanism for blood pressure regulation.

PMID- 8736048
TI  - Effect of aspirin on transiently evoked otoacoustic emissions in guinea pigs.
AB  - Aspirin and other salicylates influence otoacoustic emissions (OAEs), but changes
      in transiently evoked OAEs (TEOAEs) following aspirin intake have not been
      studied experimentally. We examined the changes in TEOAEs, together with auditory
      brainstem responses (ABRs), in guinea pigs before and after the intravenous
      injection of aspirin (100 and 400 mg/kg). TEOAE power decreased slowly after the
      injection in a dose-dependent manner. Mean minimal values were detected 20 min
      after the injection of 100 mg/kg, and 40 min after the injection of 400 mg/kg.
      TEOAE power recovered slowly. These changes were paralleled by shifts in ABR
      thresholds. The magnitude of the decrease in the frequency components in the
      TEOAE frequency power spectrum was similar. In one guinea pig, TEOAE power
      returned to the pretreatment level 7 h after the injection. Findings support the
      results of in vitro studies that salicylates affect electromotility in isolated
      outer hair cells from guinea pig cochlea.

PMID- 8736047
TI  - The effects of the purinergic system on digitalis-induced epileptiform activity.
AB  - It has been suggested that endogenous chemical substances, such as adenosine,
      released during a seizure attack, may act as anticonvulsants in vivo. We have
      investigated electrophysiologically the effects of purinoceptor agonists and
      antagonists on the epileptiform activity induced by intracortical digitalis in
      anesthetized rats. Intracortical injections of 1, 2, or 4 micrograms digitalis
      (desacetyl lanatocid C) caused an epileptiform electrocorticogram (ECoG). The
      application of adenosine (25 or 100 microM) or adenosine triphosphate (ATP) (3
      mM) after desacetyl lanatocid C blocked the epileptiform activity. beta, gamma
      Methylene ATP (0.1-0.8 mM), a stable analog of ATP, produced inhibition and then
      death. The epileptogenic effect of desacetyl lanatocid C was enhanced by
      theophylline (1 mM); however, suramin (1 mM) changed the pattern of epilepsy.
      These results indicate that the purinergic system may be involved in the
      mechanism of action of digitalis glycosides.

PMID- 8736049
TI  - Attenuation of aminoglycoside ototoxicity by glutathione.
AB  - Aminoglycoside antibiotics are commonly used for the treatment of serious gram
      negative infections despite a high incidence of associated ototoxicity. Attempts
      to elucidate the mechanisms of toxicity or prevent the adverse effects have
      previously been unsuccessful. Recently, the damaging effects of aminoglycosides
      on the inner ear have been shown to be caused by a metabolite of the drug,
      implying an enzymatic conversion of the parent compound. Glutathione has been
      suggested to be closely related to the detoxification mechanisms of this
      metabolite. This study revealed the possible attenuation of aminoglycoside
      ototoxicity by glutathione. Guinea pigs were given amikacin alone or amikacin
      with prior intramuscular injection of glutathione. The pretreatment of
      glutathione significantly reduced the damage of outer hair cells of the organ of
      Corti. This may indicate that glutathione reduces the aminoglycoside ototoxicity
      and can be favorably applied in clinical use.

PMID- 8736050
TI  - Prevalence of sensorineural hearing loss due to rubella in Saudi children.
AB  - We found positive IgM antibody against rubella virus in the blood of 23 out 1,054
      (2.2%) children (age ranged between 12 months and 14 years). Fifteen 23 infected
      children were found to have bilateral sensorineural hearing loss children of the
      at-risk group and 11 of 19 from the not-at-risk group). Hearing impairment was
      bilateral in all cases, profound in 1, moderate to severe in and mild in 5. The
      serological results of the examined children are discuss and compared with other
      reported results. The prevalence rate of rubella infection is low. This is
      attributed to the universal childhood vaccination programme compulsory for all
      Saudi children.

PMID- 8736051
TI  - Multiple-frequency tympanometry in children with otitis media with effusion.
AB  - Multifrequency tympanograms were recorded from 76 ears of 43 children affected by
      otitis media with effusion (OME) and 90 ears of normal-hearing children to obtain
      data for resonance frequency (RF) and changes in phase angle. There was found to
      be a statistically significant decrease (p < 0.01) in both RF values and change
      in phase angle in ears with OME compared to normative data. This decrease may be
      interpreted by considering OME as a mass pathology. Multiple-frequency
      tympanometry seems to be a useful method for determining the effect of various
      middle-ear pathologies on the mechano-acoustical status of the middle-ear system.

PMID- 8736052
TI  - Distribution of eosinophil granule proteins in nasal mucosa of atopic patients
      with nasal polyposis.
AB  - Nasal polyposis is characterized by heavy eosinophilic infiltration into nasal
      polyp tissue. Nasal polyps have a predilection for the anteroinferior aspect of
      the middle turbinate and middle meatal area. To elucidate the pathogenesis of
      nasal polyps, the authors investigated the distribution of eosinophil
      infiltrating into nasal polyp tissue, especially at its pedicle, in comparison
      with the apparently normal nasal mucosa of the middle and inferior turbinates of
      the same patients. Tissue samples were taken from 12 allergic rhinitis patients
      with nasal polyps during endoscopic sinus surgery. Three kinds of monoclonal
      antibodies, EG1, EG2 and BMK-13, were used for immunohistochemical staining. The
      average number per high-power field of EG1+ cells was 6.33 at the pedicle of
      polyps and 4.68 and 4.36 at the middle and inferior turbinates, respectively; for
      EG2+ cells, it was 6.16 at the polyp pedicle and 2.06 and 2.47 at the middle and
      inferior turbinates, and for BMK-13+ cells, 4.20 at the polyp pedicle and 5.17
      and 4.81 at the middle and inferior turbinates. There were no significant
      differences in the distribution of EG1+ and BMK-13+ cells, but a relatively
      larger number of activated eosinophils (EG2+ cells) was noted at the pedicle of
      polyps compared with the other sites (p < 0.025). In addition, the EG2+ cell/EG1+
      cell ratio was significantly higher at the pedicle of polyps compared with the
      other sites (p < 0.01). The results of this study suggest that the activation of
      eosinophils is significant in the pathogenesis of nasal polyps in atopic patients
      rather than the number of eosinophils.

PMID- 8736054
TI  - Diagnostic and prognostic value of nucleolar organizer regions in squamous-cell
      carcinomas of the maxillary sinus.
AB  - The clinicopathological implications of nucleolar organizer regions (NORs) were
      assessed in 25 squamous-cell carcinomas arising in the maxillary sinuses. NORs in
      the carcinoma tissue were stained with silver colloid and counted. As the
      histological differentiation of the tumors decreased, the mean AgNOR number rose
      significantly. The mean AgNOR number in T4 cancers was higher than that in T2 and
      T3 cancers, and the difference between T3 and T4 categories was significant. On
      the other hand, there were no significant differences in the AgNOR number between
      tumors of patients with and without recurrence after therapy, between those with
      different clinical stages or between those with good or poor response to
      treatment. Moreover, there was no significant difference in survival rates
      between patients with low and high AgNOR counts. These studies indicate that, in
      the collective examined, the AgNOR staining method was of no prognostic value for
      patients with squamous-cell carcinomas of the maxillary sinus.

PMID- 8736053
TI  - Comparative randomised clinical study of tolerability and efficacy of Rhinomer
      Force 3 versus a reference product in post-operative care of the nasal fossae
      after endonasal surgery.
AB  - Twenty-eight patients undergoing rhinologic surgery were enrolled in a clinical
      study to compare two post-operative cleansing preparations. Patients were asked
      to wash their nasal fossae for 1 month, either with Rhinomer, a cleansing
      preparation of isotonic, sterile, undiluted sea water, presented in slightly
      pressurised bottle with neither CFC nor preservative, or with Prorhinel, a
      marketed solution containing an antiseptic agent. Patients were randomly
      allocated to treatment beginning 2 days after surgery. Nasal status was assessed
      by symptoms (blocking nose, rhinorrhoea, sneezing, itching and impaired smell)
      and rhinologic endoscopy (colour of the nasal mucosa, swelling of the mucosa,
      secretions, presence of crusts or pus). Patients attended control visits on days
      9, 15 and 30 following surgery. They were asked to record symptom intensity and
      use of a rescue medication (Vibrocil, dimetindene 0.25 mg and phenylephrine 2.5
      mg/ml) on a diary card. Twenty-six of 28 patients were eligible for efficacy
      analysis, 14 in the Rhinomer group and 12 in the Prorhinel group, In both groups,
      intensity of complaints decreased markedly over the study period. No severe
      adverse drug reactions were reported in either treatment. Evoked complaint
      frequency was comparable between groups, but patient's and physician's opinion on
      tolerability was significantly different between treatments, in favour of
      Rhinomer. In addition, the test preparation was found to be easier to use than
      Prorhinel. The weekly average frequency of use of the rescue medication was not
      significantly different between treatments. When both patients and physicians
      were asked about treatment efficacy, they expressed an opinion significantly more
      favourable to Rhinomer than to the reference drug. In this study, Rhinomer has
      shown efficacious results that justify its use in washing of the nasal cavities
      following endonasal surgery.

PMID- 8736055
TI  - Laser-uvulopalatoplasty (LUPP) under local anesthesia: effective, safe and
      comfortable.
AB  - Conventional uvulopalatopharyngoplasty has in the last years to an increasing
      extent been succeeded by a variety of laser procedures for snorers obstructed by
      lax palates only. These surgical techniques have the advantages of being less
      traumatic and therefore more suitable for local anesthesia and outpatient
      surgery. However, to the authors' knowledge, there are no studies on degree of
      patient discomfort during this type of surgery as well as the value of
      anticholinergic component in premedication in preventing bradycardia and
      hypersalivation during the operation. We studied 53 consecutive patients
      undergoing laser-uvulopalatoplasty (LUPP) under local anesthesia at our day care
      unit. LUPP is a one-stage operation for rhonchopathy which has been developed at
      our department. Twenty-five patients received morphine and scopolamine, and 28
      morphine alone as premedication. Peroperative salivation, bradycardia and nausea
      was estimated and recorded for each group. Later the patients were asked to
      assess mouth dryness both before and after surgery, as well as satisfaction with
      sedation and pain relief. The great majority of the patients (> 80%) described
      only insignificant pain, which when occurring was related to subliminal
      premedication or to the injection of local anesthesia or both. Morphine
      scopolamine was significantly better in preventing hypersalivation (p < 0.01)
      during surgery and also improved sedation and analgesia when compared to morphine
      alone (p < 0.05). The efficacy of LUPP is compared with various laser procedures
      for snoring.

PMID- 8736056
TI  - Endoluminal ultrasonography: a new method to evaluate dysphagia.
AB  - Dysphagia consists of various diseases, which all lead to an impaired quality of
      life. Besides a thorough case history and clinical examination, there is a need
      for objective diagnostic examinations to evaluate the extent of the disease. The
      present study includes 38 patients suffering from the most common causes of
      dysphagia such as benign or malignant strictures of the esophagus, esophagitis,
      achalasia cardiae, cricopharyngeal dysfunction and motility disorders. The
      patients were examined by endoluminal ultrasonography using a 2.7 mm-wide-probe.
      The present study clearly indicates the value of the method in evaluating the
      extent of the disease in patients suffering from the aforementioned diseases.

PMID- 8736057
TI  - Study on orthostatic dysregulation and the Schellong test in healthy young
      females.
AB  - We carried out a questionnaire survey regarding the symptoms of orthostatic
      dysregulation (OD) and administered the Schellong test to 301 healthy young
      females ranging in age from 18 to 21 years. OD was identified in 62 (20.6%) of
      the subjects based on the questionnaire. Although orthostatic dizziness was
      relatively common in the entire group of young females (171/301, 56.8%), this
      symptom was much more prevalent in the subjects with OD (58/62, 93.5%). There was
      also a highly significant difference between the systolic pressure decrease
      during the Schellong test procedure in 22 subjects with OD with frequent
      orthostatic dizziness and that in the 239 subjects without OD. Although the
      clinical value of the Schellong test in the assessment of OD and other related
      conditions has been brought into question because of its relatively poor
      specificity, we conclude that this test procedure may be useful in screening for
      OD or autonomic nerve dysfunction, since it presents the advantage of easy
      application in clinical practice.

PMID- 8736058
TI  - Leiomyosarcoma of the nasal cavity. Case report and literature review.
AB  - Leiomyosarcoma (LMS) accounts for approximately 7% of all soft tissue sarcomas
      and occurs most frequently in the gastrointestinal tract and uterus. LMS of the
      nasal cavity and paranasal sinuses are rare and only about 40 cases of LMS of the
      nose and paranasal sinuses have been reported in the literature. A further case
      of LMS of the right turbinate is presented, treated twice by surgery. To date,
      the patient has been free of disease for more than 48 months. The symptoms,
      pathology, treatment and prognosis, and origin of this tumor are discussed.
      Initially, LMS should be treated by extensive surgical excision, but long-term
      follow-up is essential due to the high rate of local recurrence. Radiotherapy and
      chemotherapy are insufficient therapeutic approaches. Frequency of recurrence and
      prognosis depend on the tumor site. The prognosis of LMS of the nasal cavity is
      better than LMS of the paranasal sinuses.

PMID- 8736059
TI  - Topics in xenobiochemistry--application of microdialysis techniques in
      pharmacokinetic studies.
AB  - The principle of the microdialysis technique, the microdialysis system and its
      application to pharmacokinetic studies is discussed. By applying the
      microdialysis technique to pharmacokinetic studies the number of animals needed
      can be substantially reduced, because the technique involves a sampling technique
      which does not withdraw body fluid and so does not disturb blood homeostasis.
      Therefore, there are no limiting factors to the amount of samples taken from one
      animal. The utility offered by the microdialysis technique will have a bearing on
      future pharmacokinetic studies and it is to be expected that the importance of
      microdialysis in pharmacokinetic studies will grow in the future.

PMID- 8736060
TI  - Murine cytochrome P4503A is induced by 2-methyl-3-buten-2-ol, 3-methyl-1-pentyn-3
      ol(meparfynol), and tert-amyl alcohol.
AB  - 1. Colupulone, a constituent of hops, was shown to be a potent inducer of hepatic
      P4503A in mouse. The olefin, 2-methyl-3-buten-2-ol (RC = CH2), is formed from
      lupulones when hops are exposed to atmospheric hydroxyl radicals. This suggested
      the possibility that the same reaction may occur in vivo. The credibility of this
      hypothesis was enhanced when RC = CH2 was shown to induce P4503A in mouse.
      Ethylmorphine (EM) N-demethylation, a functional marker for P4503A, was also
      induced by RC = CH2. 2. 3-Methyl-1-pentyn-3-ol (RC identical to meparfynol), a
      sedative and close structural analogue of RC = CH2, also induced P4503A and EM N
      demeythylation. Tert-amyl alcohol (RC-CH3), the saturated analogue of RC = CH2,
      was included in t he study with the expectation that it would serve as a negative
      control for the anticipated induction of P4503A by the other two alcohols. This
      proved not to be the case; RC-CH3 was about as active an inducer of P4503A as RC
      = CH2 and RC identical to CH. The possibility is considered that, like valproic
      acid, RC-CH3 is metabolized to an olefin by P450. 3. Hydroxylation of aniline and
      benzo[a]pyrene by hepatic microsomes from mice treated with the three alcohols
      were used as functional markers for the induction of P4502E and P4501A
      respectively. RC = CH2 at the two lowest levels of administration suppressed
      aniline hydroxylation but had no effect at the highest level. RC identical to CH
      was ineffective and RC-CH3 was moderately inductive at all three levels. Each of
      the three compounds were weak to moderate inducers of benzo[a]pyrene
      hydroxylation.

PMID- 8736061
TI  - Formation of 2-sulphamoylacetylphenol from zonisamide under aerobic conditions in
      rat liver microsomes.
AB  - 1. The antiepileptic agent zonisamide, 1,2-benzisoxazole-3-methanesulphonamide,
      was metabolized reductively to 2-sulphamoyl-acetylphenol (SMAP) not only under
      anaerobic conditions but also under aerobic conditions in liver microsomes of rat
      pretreated with phenobarbital or dexamethasone. 2. NADPH was required for the
      formation of SMAP from zonisamide under aerobic conditions. In addition, the
      reductive metabolism of zonisamide under these conditions was substantially
      inhibited by carbon monoxide, ketoconazole, and cimetidine, known inhibitors of
      cytochrome P450. 3. The formation of SMAP under aerobic conditions in liver
      microsomes was increased by pretreatment of rat with triacetyloleandomycin (TAO)
      and was increased by the treatment of the microsomes with ferricynaide. 4. These
      results imply that zonisamide is metabolized reductively to SMAP by a cytochrome
      P450 belonging to the 3A subfamily under aerobic conditions as well as anaerobic
      conditions.

PMID- 8736062
TI  - Lack of effect of methotrexate on the expression of constitutive hepatic
      cytochromes P450 in the male rat.
AB  - 1. The effects of methotrexate (MTX) on the expression of selected constitutive
      cytochrome P450 (CYP) isozymes in the liver of male rats at the catalytic
      activity and mRNA levels were examined. 2. Male rats received a single
      intraperitoneal injection of MTX (4 mg/kg) or vehicle and were killed, 1, 2, 7 or
      14 days following drug administration. 3. Hepatic microsomes were used for
      determination of total CYP content, NADPH-CYP reductase activity, aminopyrine N
      demethylase activity, and androstenedione (AD) hydroxylation activity; total RNA
      was also isolated from liver and was used for hybridization analysis of CYP
      isozyme expression at the mRNA level. 4. MTX did not affect any of the following
      parameters at any time-point in comparison with the corresponding vehicle
      control: body weight, liver weight, hepatic microsomal protein content, total CYP
      content, NADPH-CYP reductase activity, aminopyrine N-demethylase activity, AD 6
      beta- and 7 alpha-hydroxylase activity, and CYP3A2 mRNA content. 5. The major
      male-specific CYP isozyme, 2C11, was down-regulated by MTX treatment as revealed
      by a marginal (25%), but statistically significant decrease in AD 16 alpha
      hydroxylase activity at day 14 and a marginal (18%), but statistically
      significant decrease in CYP2C11 mRNA content at day 14. 6. In comparison with
      other antineoplastic drugs that have been examined, MTX appears to possess a
      lesser capacity for modulation of hepatic CYP enzymes.

PMID- 8736063
TI  - Pharmacokinetics of ethylene glycol. III. Plasma disposition and metabolic fate
      after single increasing intravenous, peroral, or percutaneous doses in the male
      Sprague-Dawley rat.
AB  - 1. The pharmacokinetic fate of [1,2-14C]-ethylene glycol (EG) was evaluated in
      the male Sprague-Dawley rat in order to characterize its overall uptake and
      elimination. Doses of 10 and 1000 mg/kg were administered by the intravenous
      (i.v.), peroral (p.o.), or percutaneous (p.c.) route; additional doses of 400,
      600 and 800 mg/kg were evaluated by the p.o route. 2. Baseline data obtained by
      the i.v. route for bioavailability comparisons showed that while plasma
      radioactivity concentrations declined in a biexponential manner with t1/2 beta of
      26-37 h, the disappearance of unmetabolized EG from the plasma was quite rapid
      (t1/2 beta of 0.8-1.2 h). Peroral doses were rapidly and almost completely
      absorbed, showing t1/2 abs in the order of minutes, and a bioavailable fraction
      for unmetabolized EG of 92-100%. Conversely, EG applied to rat skin was slowly
      and rather poorly absorbed, showing t1/2 abs which were an order of magnitude
      longer than for comparable p.o. and i.v. doses, and a bioavailability of
      approximately 22%. 3. The major route of elimination for the 10 mg/kg dose by any
      route was by metabolism to 14CO2 and exhalation, while urinary elimination of 14C
      was the secondary excretion pathway. 4. Plasma clearance of 14C was linear with
      increases in p.o. doses over the 400-800 mg/kg range, with AUC proportional to
      dose for these and the 10 mg/kg p.o. dose levels. However, a dose-dependent shift
      in excretion routes was observed following the p.o. 1000 mg/kg dose, with urine
      becoming the major excretion route, and similar capacity limited pharmacokinetics
      were observed for the i.v. 1000 mg/kg dose. Plasma pharmacokinetic data for
      unchanged EG after i.v. and p.o. doses demonstrated an apparent first-order
      kinetic behaviour between the 10 and 1000 mg/kg dose levels for the disappearance
      of EG. 5. Following both i.v. and p.o doses, dose-independent relationships were
      seen in the values obtained for the area under the plasma curve (AUC infinity),
      the total clearance of EG (CltotalEG), mean residence time (MRT infinity),
      apparent volume of distribution at steady state (Vdss), the terminal half-life
      (t1/2 beta) and the renal and metabolic clearance values. However, this dose
      linear plasma time course was not apparent from the dose-dependent excretion
      profiles for these two exposure routes. 6. Increases in urinary 14C-glycolate
      were also observed when the i.v. or p.o. doses were increased from 10 to 1000 mg
      EG/kg, indicating that metabolism of EG makes a substantial contribution to AUC
      infinity in the beta disposition phase of the plasma curves for this high dose.
      Oxalate, a metabolite found in man after EG exposure, was detected at very low
      levels after both the 10 and 1000 mg/kg dose levels and by either i.v or p.o.
      routes. 7. Thus, EG given by three different routes demonstrated apparent first
      order pharmacokinetic behaviour for disposition in and the elimination from
      plasma in the male rat, but dose-dependent changes occurred for the elimination
      of metabolites in urine and as 14CO2 after single i.v. and p.o. doses, but not
      for the p.c. routes.

PMID- 8736064
TI  - Application of electrospray mass spectrometry in the identification of intact
      glucuronide and suplate conjugates of clozapine in rat.
AB  - 1. The phase II metabolites in the bile, urine and faeces of rat dosed with
      clozapine were investigated by means of electrospray mass spectrometry (ESMS) in
      both positive and negative ion modes. 2. When operated at a cone voltage of 45 V,
      this soft ionization technique permitted the detection of quasi molecular ions of
      both sulphate and glucuronide conjugates of hydroxylated phase I metabolites of
      clozapine. With the cone voltage set at 90 V, however, the ESMS also contained
      highly diagnostic ions resulting from the loss of 80 Daltons (sulphur trioxide)
      or 176 Daltons (the glucuronide moiety) from sulphates and O-glucuronides
      respectively. 3. A sufficient quantity of one metabolite was isolated from rat
      bile to permit further analysis by 1H-nmr. This metabolite, which was also found
      in rat urine, was proved to be 7-O-glucuronyl-7-hydroxyclozapine. The analogous
      sulphate metabolite was also identified in bile by ESMS. 4. Correspondingly
      glucuronide and sulphate conjugates of a hydroxylated N-desmethyl clozapine were
      similarly detected in rat bile. There was insufficient material to permit
      analysis by 1H-NMR, but it appears likely that conjugation was also at the 7
      position of N-desmethylclozapine. 5. Finally, the sulphate conjugate of a hydroxy
      dechlorinated derivative of clozapine was identified by ESMS in both urine and
      bile. By analogy with a previous report of a similar metabolite in man, the
      metabolite was tentatively identified as 8-hydroxy-8-deschloroclozapine.

PMID- 8736065
TI  - Reductive metabolism and its role in the disposition of the hydroxamic
      angiotensin-converting enzyme inhibitor idrapril calcium in rat.
AB  - 1. The metabolism of 14C-idrapril calcium, the prototype of a new class of
      angiotensin-converting enzyme inhibitors, was studied in rat after a single
      intravenous administration. Plasma, urine, faeces, and bile were assayed for
      total and hplc-fractionated radioactivity. 2. Only one major metabolite (M1, 2
      sarcosinamide-cis-1,2-cyclohexanedicarboxylamide) was observed, along with
      idrapril, in plasma. Three metabolites (M1, M2, cis-1,2-cyclohexanedicarboxylic
      acid, and M3, a glucuronate derivative of M1) were present in 0-8-h urine,
      unchanged idrapril being the most abundant product. In bile, two metabolites (M1,
      M3), but not the parent compound, were found. 3. In conclusion intravenous
      idrapril undergoes hepatic reduction to M1 and hydrolysis to M2. M1 can be
      glucuronated to M3 and both are partially excreted in the bile and further
      processed in the gut to reabsorbable radioactive species.

PMID- 8736066
TI  - Effect of substituents on the metabolism of nitracrine in rat.
AB  - 1. Male Wistar rats were treated with either the antitumour agent nitracrine (1
      nitro-9-(3'-dimethylamino-N-propylamino)-acridine; NC), 4-methoxy-NC, NC
      aliphatic-N-oxide, 4-methoxy-NC-aliphatic-N-oxide, or NC-aromatic-N-oxide (30
      mumol/kg, via the femoral vein) and the major biliary and urinary metabolites
      analysed by hplc. 2. No NC or 4-methoxy-NC were detected in bile or urine of rat
      treated with NC or 4-methoxy-NC respectively, whereas the aliphatic N-oxides of
      NC and 4-methoxy-NC were recovered largely unchanged in both bile and urine. 3.
      NC-aromatic-N-oxide was rapidly and extensively converted to a major polar
      biliary product. This product was also synthesised enzymatically from NC-aromatic
      N-oxide using rat liver cytosol and has been identified by mass and 1H-nmr
      spectrometry as 1-(S-glutathionyl)-9-(3'-dimethylamino-N-propylamino)-acridine
      N(10)-oxi de. 4. The equivalent 1-(S-glutathionyl) conjugate appears to be formed
      from NC, and excreted in bile as a minor product, but not from 4-methoxy-NC.
      Further experiments with cytosol indicate that direct displacement of the nitro
      group by GSH is mediated by GSH transferase. 5. Finally, the major biliary
      metabolite of NC has been provisionally identified as a glucuronide of 1-nitro-2
      hydroxy-NC. 6. It is concluded that, for at least a significant fraction of NC,
      nitroreduction does not occur. Further, N-oxidation of the aliphatic (but not the
      aromatic ring) nitrogen, plus 4-methoxy substitution, decreases the overall
      metabolism of NC in the rat.

PMID- 8736067
TI  - Chemical defibrillation in acute myocardial ischaemia: a hypothesis.

PMID- 8736068
TI  - Anions, membrane resistance and ventricular fibrillation.
AB  - Clinical success in prevention of sudden cardiac death has been poor. New
      approaches to prevention of ventricular fibrillation (VF), one of the main causes
      of sudden cardiac death, are clearly needed. In the present article we have
      reviewed some of our own data which support the notion that VF may be prevented
      by manipulation of chloride homeostasis. Our studies have revealed a novel
      approach to VF suppression via alteration of sarcolemmal membrane resistance.

PMID- 8736069
TI  - Ion-selective channels in K562 cells: a patch-clamp analysis.
AB  - Four types of ion-selective channels were found by the patch-clamp technique in
      the human erythroleukemia K562 cells. I) in cell-attached configuration at
      potentials less negative than -40 mV an 8 ps channel was detected. The potential
      dependence of channel activity suggests that this is the TTX-sensitive Na+
      channel. II) A cation-selective channel was observed with equal permeability for
      Na+ and K+ and a potential-independent single-channel conductance of 19 pS. The
      channel is activated by intracellular Ca2+ and inhibited by TEA, III) A
      predominantly anion-selective channel was identified with the selectivity
      sequence NO3- > J- > Cl- = Br- >> SO4(2-). The single-channel conductance shows
      outward rectification, and is in symmetrical NaCl solution 19 pS at -60 mV and
      54pS at +50 mV. The open- and closed-time distributions suggest one open and at
      least four closed states. At submicromolar concentrations, the open state is
      blocked by H2DIDS leading to channel flicker between open and blocked channel;
      higher concentrations (apparent KI = 6.8 uM) lead to a longer-lasting blocked
      state. Both components of inhibition are reversible. IV) In addition, an 8 pS,
      Na(+)- and K(+)- selective channel could be induced by application of palytoxin.
      For channel activity, the presence of extracellular Na+ is essential. It is
      assumed that the Na+, K(+)-pump molecule is involved in the channel formation.
      Similarly, it is discussed whether the anion-selective channel represents a pore
      conformation of an electrically silent anion exchanger.

PMID- 8736070
TI  - Magnesium protects against anaphylactic shock and cardiac myolysis in guinea
      pigs.
AB  - The pathophysiological responses to immune stress (IS) include activation of
      several processes which are dependent on cytosolic Ca2+ elevation. Magnesium
      frequently acts as a natural Ca2+ antagonist. In this study we have observed that
      Mg2+ can protect guinea-pigs against IS. Antigen-sensitized guinea-pigs, which
      had been fed a magnesium-deficient diet, were given a single dose (15 mg) of
      MgCl2 intraperitoneally 1 h before antigen challenge. The development of
      anaphylactic shock (AS) was observed during the next 2 h, and the hearts were
      subsequently examined histologically for signs of cardiac myolysis (CM).
      Magnesium (i) reduced the incidence of CM from 40% to 10% (p < 0.05); (ii)
      reduced the incidence of AS from 61% to 35% (p < 0.05); (iii) attenuated the
      severity of the AS; and (iv) lowered mortality from 39% in the control to 19% in
      the Mg(2+)-treated group (p = 0.1). Serum and tissue total [Mg2+] were not
      affected by the administration of MgCl2. Also, the serum and heart Mg2+ levels
      were the same whether or not the guinea-pigs developed AS or CM. In cell culture
      we demonstrated that by elevating the [Mg2+] in the medium bathing sensitized rat
      basophilic leukemia (RBL) cells, the increase in cytosolic [Ca2+] subsequent to
      antigen challenge was reduced from 174 +/- 23.28% (1 mM) to 82.74 +/- 13.22% (3
      mM). We conclude that a single treatment with Mg2+ can considerably diminish
      damage induced by immune stress, probably by its altering the Ca2+: Mg2+ ratio.
      Since the physiological reaction to different types of stress is similar, Mg2+
      could prove beneficial in preventing stress-induced shock in general. Studies
      examining the mechanisms by which Mg2+ exerts its effects thus provide a
      scientific basis for the current clinical use of Mg2+ in acute myocardial
      infarction (AMI) and asthma.

PMID- 8736073
TI  - Dehydration and rehydration in donkeys: the role of the hind gut as a water
      reservoir.
AB  - Body fluid distribution was measured in three donkeys, fully hydrated, following
      dehydration and after being rapidly rehydrated. In twenty other donkeys that were
      slaughtered to supply food for predators in a safari zoo, the water content in
      the different compartments of the gastrointestinal tract (GIT) was assessed.
      Prior to being slaughtered, four of the animals were fully hydrated, four
      dehydrated and 12 dehydrated, rehydrated and then slaughtered and examined, four
      at 1, for at 3 and four at 5 hours following drinking. When the body mass of
      dehydrated donkeys dropped to 75.4 +/- 2.4% of their initial value, total body
      water of the animals (HTO space), extracellular volume (SCN space) and plasma
      volume (EB space) were reduced to 76.6 +/- 5.3%, 80.9 +/- 10.6% and 73.2 +/- 8.3%
      of their initial values, respectively. The amount of water retained in the GIT of
      the fully hydrated donkeys amounted to 15.9 +/- 3.4 1, 19% of total body water.
      In the dehydrated donkeys it was only 7.4 +/- 1.3 1. The calculated total
      intracellular volume in the dehydrated donkeys was only 14% lower than in the
      fully hydrated animals. When drinking was allowed, dehydrated donkeys consumed
      17.6 +/- 2.4 1 of water. The increase in the water content in the gut of newly
      rehydrated donkeys matched this volume, 80% of which was retained in the hind
      gut. During the five hours after drinking, only slow and moderate changes in the
      volume of the hind gut were recorded. Changes in plasma volume were also
      suppressed. It is suggested that the hind gut of the donkey, similar to the rumen
      of goats and sheep, plays a role as a water reservoir that helps maintain the
      osmotic stability of the body.

PMID- 8736072
TI  - Oxygen toxicity as a function of time and PO2.
AB  - The quantification of O2 toxicity as a function of exposure time (t) and PO2 has
      been based mainly on the empirical rectangular hyperbola. The non-linear response
      of the O2-damaged physiological variable (DMG) as a function of time at constant
      PO2 can be related to the dependence of dDMG/dt on the DMG. The kinetics of the
      O2-derived chemical species suggests a power relationship between the DMG and PO2
      rather than a linear relationship. The combination of time and PO2 considerations
      suggests two models: 1) DMG = a(ebt - 1) PO2c and 2) DMG = a.tbPO2c, where a, b
      and c are constant. Non-linear regression of the different parameters of O2
      toxicity showed a preference for model 2, with b = 2. Possible mechanisms
      underlying the kinetics of O2 toxicity and the use of the equation for its
      prediction are discussed.

PMID- 8736071
TI  - A new class of antiarrhythmic--defibrillatory compounds.
AB  - Ventricular fibrillation (VF) is a major cause of sudden cardiac death in humans.
      Currently used antiarrhythmic drugs are aimed at preventing initiation of VF by
      decreasing the incidence of arrhythmias which can lead to VF. This approach today
      seems to be insufficient. On the basis of reports that VF can terminate
      spontaneously in various mammals, and even in humans, we propose pharmaceutical
      enhancement of self-ventricular defibrillation as a new therapeutical approach.
      Data obtained over the last decade indicate that a high cardiac extraneuronal
      noepinephrine level during VF facilitates self-defibrillation. Dibenzazepines
      (tricyclic antidepressants) and phenothiazines elevate norepinephrine level by
      inhibiting norepinephrine reuptake and were found to exhibit defibrillatory
      activity. The relationship of chemical structure to defibrillatory activity was
      studied in a group of dibenzazepine and phenothiazine compounds.

PMID- 8736074
TI  - Doctors against smoking.

PMID- 8736075
TI  - Strengths and weaknesses of screening programmes for oral malignancies and
      potentially malignant lesions.
AB  - Screening for oral cancer is in an early stage of development. No randomized
      controlled trials have been undertaken to determine the impact of screening on
      mortality or even on interim outcomes such as incidence or down-staging. Until
      such data are available, mass screening for oral cancer is not recommended as
      public health policy. Case finding studies to identify individuals at risk
      because of life-style, and to detect potentially malignant oral mucosal changes
      followed by appropriate intervention may, however, reduce the future incidence of
      oral cancer. Where manpower is available, opportunistic screening focused on high
      risk subjects may be beneficial.

PMID- 8736076
TI  - Endometrial cancer in a cohort screened for breast cancer.
AB  - In a cohort of 25,000 women aged 40-65 years at intake in a periodic screening
      programme for breast cancer the occurrence of endometrial cancer was studied
      during a follow-up period of up to 18 years. The authors examined whether they
      could confirm the existence of a number of relationships between this cancer and
      some reproductive and anthropometric factors which had been found in several case
      control studies and in a few cohort studies. A comparison was made between 147
      cases of endometrial cancer occurring during the period of follow-up and a random
      sample of 900 women taken from the cohort (334 being premenopausal and 566
      postmenopausal on the day of intake). An inverse relationship between number of
      children and endometrial cancer risk was found in the older group; the excess
      risk among nulliparous women was stronger in married than in single women. Late
      age at menopause (after age 52) was associated with increased risk. Use of
      oestrogenic drugs on day of intake for alleviating perimenopausal complaints
      (reported in 8% of women) increased risk, especially in the younger group. Body
      weight was positively associated with risk (with an odds ratio of 4 in those over
      80 kg) among postmenopausal women. Because there appeared to be a moderately
      strong risk associated with tall height, especially among postmenopausal women,
      Quetelet's index performed less well than body weight itself. Nevertheless,
      subscapular and triceps skinfold thicknesses confirmed an effect of fatness on
      risk. These results are discussed with reference to other epidemiological
      studies, in particular two cohort studies from Norway. The effect of height,
      convincingly shown by Tretli and Magnus in 1990, is explained in a way which does
      not assume causal mechanisms operating at a young age: absolute fat mass rather
      than relative weight is regarded as the main determinant of risk in
      postmenopausal women.

PMID- 8736078
TI  - An ecological study of the correlation between diet and tumour mortality rates in
      Italy.
AB  - Cancer is said to be due to nutrition in 35 cases out of 100, ranging from 10 to
      70% by sites. Saturated fats show a positive relationship with cancer, while
      vitamins, vegetables and cereals show a negative relation with it. This work was
      aimed at studying the relationship between nutrition and cancer in different
      Italian areas. Cancer mortality rates collected in 94 National Health units over
      the period 1980-82 have been correlated with the average food consumption of
      individuals registered in the same units. All the nutrient groups have shown
      evidence of a correlation between nutrient intake and mortality rates. Fats,
      animal proteins and saturated fatty acids showed the strongest positive
      correlations; vegetable proteins, fibre, carbohydrates, oleic acid, vitamins C
      and B1 gave negative correlations. Thus, it can be concluded that (a) this
      ecological analysis has confirmed previous hypotheses concerning the role of
      vegetables in cancer prevention and (b) the relation between nutrition and cancer
      mortality could be even stronger if applied to the whole population, since a 1-g
      increase in vegetable protein consumption would result in a reduction of 2.5
      cases out of 100, a 1-g increase in fibre would result in a reduction of four
      cases out of 100 and a 1-g increase in animal fat would result in an increase of
      one case out of 100.

PMID- 8736077
TI  - A comparative study of risk factors for hyperplasia and cancer of the
      endometrium.
AB  - A cohort study has been carried out to investigate risk factors for cancer as
      well as hyperplasia of the endometrium. Over the 13 years for which we followed
      25,000 women aged 40-65 (who took part in a population-based screening programme
      for breast cancer), 111 cases of endometrial cancer and 109 cases of endometrial
      hyperplasia were diagnosed. A comparison of the outcome between the two disease
      entities revealed that large body weight among postmenopausal women and the use
      of oestrogenic drugs at all ages were risk factors for both cancer and
      hyperplasia of the endometrium. However, reproductive histories and premenopausal
      steroid profiles differed. Steroid excretion determinations in urine samples
      collected years before diagnosis provided further evidence in favour of the
      hypothesis of unopposed action of oestrogens in the aetiology of endometrial
      cancer. In women who were to develop endometrial hyperplasia or cancer the
      obesity-oestrogen relationship was stronger than in those who remained free of
      endometrial disease during the period of follow-up. The possible significance of
      differences in aromatase activity among the obese is considered.

PMID- 8736079
TI  - New concept for cancer screening.
AB  - Prevention of cancer mortality can be achieved by two main routes: (1) detection
      of precancerous lesions and preventing their progression to cancer, and (2)
      detecting cancers at an early stage when they are still amenable to curative
      treatment. Early detection of cancer is dependent on the population being well
      informed about cancer, and about how to carry out self-examination as a
      preliminary screen (followed by a full clinical examination in the event of
      suspicious symptoms). In this paper the warning signs that the population should
      be taught to look out for are discussed. Superficial observation and palpation
      can be used for surface tumours (which comprise 10-15% of the total). A further
      60-70% of tumours are of the digestive tract, respiratory tract or urogenital
      tract. For these, it is argued that a simple occult blood test could be used as a
      self-administered screening test. Data are presented to show that this is a
      practicable way for the general population to detect early signs of cancer or pre
      cancer, with a high yield of clinically significant results in the occult blood
      positive persons.

PMID- 8736080
TI  - Salmonella carrier state, chronic bacterial infection and gallbladder
      carcinogenesis.

PMID- 8736081
TI  - Man-biting activity of Anopheles (Nyssorhynchus) albimanus and An. (Kerteszia)
      neivai (Diptera: Culicidae) in the Pacific lowlands of Colombia.
AB  - The daily man-biting activity of Anopheles (Nyssorhynchus) albimanus and An.
      (Kerteszia) neivai was determined in four ecologically distinct settlements of
      the Naya River, Department of Valle, Colombia. Differences were found among the
      settlements with respect to the mosquito species present, intradomiciliary and
      extradomiciliary biting activity and population densities.

PMID- 8736082
TI  - Human parvovirus B19 infection and hydrops fetalis in Rio de Janeiro, Brazil.
AB  - Formalin-fixed paraffin embedded lung and liver tissue from 23 cases of non
      immune hydrops fetalis and five control cases, in which hydrops were due to
      syphilis (3) and genetic causes (2), were examined for the presence of human
      parvovirus B19 by DNA hybridisation. Using in situ hybridisation with a
      biotynilated probe one positive case was detected. Using 32P-labelled probes in a
      dot blot assay format, five further positives were obtained. These were all
      confirmed as positive by a nested polymerase chain reaction assay. Electron
      microscopy revealed virus in all these five positive cases. The six B19 DNA
      positive cases of hydrops fetalis were from 1974, 1980, 1982, 1987 and 1988, four
      of which occurred during the second half of the year, confirming the seasonality
      of the disease.

PMID- 8736083
TI  - Onchocerciasis in Ecuador: changes in prevalence of ocular lesions in Onchocerca
      volvulus infected individuals over the period 1980-1990.
AB  - Trends in prevalence rates of onchocercal ocular lesions were examined over the
      period 1980 to 1990 using data from two cross-sectional surveys. There was
      evidence for increasing prevalence of anterior chamber microfilariae,
      iridocyclitis, optic atrophy, and chorioretinopathy. Large increases in
      prevalence, in particular, were seen for posterior segment lesions: optic atrophy
      increased from 2.7% to 6.4% and chorioretinopathy from 8.8% to 35.6%. Greatest
      increases in these lesions were seen in the Chachi which was attributed to the
      large increases in prevalence of microfilariae in the anterior chamber
      particularly in those aged 30 years or greater. The study findings suggest that
      ocular onchocerciasis is evolving in parallel with the well documented
      parasitological changes.

PMID- 8736084
TI  - Biological control of Aedes albopictus (Diptera: Culicidae) larvae in trap tyres
      by Mesocyclops longisetus (Copepoda: Cyclopidae) in two field trials.

PMID- 8736085
TI  - Redescription of Lutzomyia (Lutzomyia) souzalopesi Martins, Silva & Falcao, 1970
      (Diptera, Psychodidae, Phlebotominae).
AB  - The authors redescribe the male and the female of Lutzomyia (Lutzomyia)
      souzalopesi Martins, Silva & Falcao, 1970. Taxonomic remarks, geographic
      distribution and drawings are presented.

PMID- 8736086
TI  - Neotropical planorbid snails with apertural lamellae. I. Biomphalaria helophila
      (Orbigny, 1835).
AB  - A definition of Biomphalaria helophila (Orbigny, 1835) is presented, based on
      examination of the shell and reproductive system of topotypic specimens and
      extended to a number of samples from other localities. The following nominal
      species and subspecies, collected from type localities, proved junior synonyms of
      B. helophila. Planorbis albicans Pfeiffer, 1839, Planorbis dentatus Gould, 1844;
      Planorbis dentiferus CB Adams, 1845; Planorbis dentiferus edentatus CB Adams,
      1851; Planorbis dentiens Morelet, 1849; Planorbula dentiens edentula Fischer &
      Crosse, 1880; Planorbis stagnicola Morelet, 1851; and Tropicorbis shimeki FC
      Baker, 1945. B. helophila was also identified in samples from Costa Rica,
      Guatemala, Haiti, Dominican Republic, Puerto Rico and Barbados.

PMID- 8736087
TI  - Biomphalaria subprona (Martens, 1899) (Gastropoda: Planorbidae).
AB  - A description is given of the shell, head-foot, pulmonary wall, reproductive
      system and radula of Biomphalaria subprona (Martens, 1899). A diagnosis between
      it and two other congeneric species under 10 mm in shell diameter occurring in
      Middle America (Biomphalaria helophila and B. schrammi) is presented.

PMID- 8736089
TI  - Montenegro skin test--evaluation of the composition and stability of the antigen
      preparation.

PMID- 8736088
TI  - Evaluation of enzyme-linked immunosorbent assay for the serodiagnosis of
      tuberculosis in patients with AIDS in Cuba.

PMID- 8736090
TI  - The use of polyvinyl alcohol glutaraldehyde as solid-phase in ELISA for plague.
AB  - Discs of polyvinyl alcohol cross-linked with glutaraldehyde were synthesized
      under acid catalysis (H2SO4). Then, the antigen F1 purified from Yersinia pestis
      was covalently linked to this modified polymer. Afterwards, an enzyme-linked
      immunosorbent assay (ELISA) was established for the diagnosis of plague in rabbit
      and human. The best conditions for the method were achieved by using 1.3
      micrograms of F1 prepared in 0.067 M phosphate buffer, pH 7.2, containing 1 M
      NaCl (PBS); anti-IgG peroxidase conjugate diluted 6,000 times and as a blocking
      agent 3% w/v skim milk in PBS. The titration of positive rabbit serum according
      to this procedure detected antibody concentrations up to 1:12,800 times. The
      present method, the conventional ELISA and passive haemagglutination assay are
      compared.

PMID- 8736091
TI  - Evaluation of the rabbit as a model for Chagas disease-II. Histopathologic
      studies of the heart, digestive tract and skeletal muscle.
AB  - In order to investigate the value of the rabbit as an experimental model for
      Chagas' disease, seventy one animals were inoculated with different Trypanosoma
      cruzi strains and routes. The rabbits were submitted to necropsy in acute
      (earlier than three months of infection), recent chronic (three to six months)
      and late chronic (later than six months) phases. Myocarditis, generally focal and
      endomysial, occurred in 94.1%, 66.7% and 70.8% of the infected rabbits
      respectively in the acute, recent chronic and late chronic phases. The myocardial
      inflammatory exudate was composed by mononuclear cells, and also
      polymorphonuclear cells in the acute phase. In most cases of the late chronic
      phase, the myocarditis was similar to that described in the indeterminate form of
      human chagasic patients. Initial fibrosis occurred in the three phases but was
      more severe and frequent in the early chronic. Advanced fibrosis occurred only in
      the late chronic phase. Tissue parasites occurred only in the acute phase. The
      digestive tract and skeletal muscles showed mild and occasional lesions. Our data
      indicate that experimentally infected chagasic rabbits repeat some lesions
      similar to that of humans chagasic patients, specially that of the indeterminate
      form. So, it may be a useful, however not an ideal, model.

PMID- 8736092
TI  - High and low doses of antimony (Sbv) in American cutaneous leishmaniasis. A five
      years follow-up study of 15 patients.
AB  - Seventeen patients proceeding from the municipality of Rio de Janeiro, Brazil
      presenting with the cutaneous ulcerative form of American leishmaniasis were
      treated with one ampoule of pentavalent antimony daily for 30 days. With this
      regimen the individuals doses varies greatly: from 3.8 mg/kg of body weight to
      22.3 mg/kg. After five years, patients receiving either a smaller dose or a
      bigger one, showed the same therapeutic result: cutaneous scars and no mucosal
      lesions.

PMID- 8736093
TI  - Trypanosoma cruzi infection in offspring born to chagasic C3H/He mice.
AB  - This study reports the effects of Trypanosoma cruzi infection induced in C3H/He
      male and female mice born to chagasic mice. An experimental model was established
      infecting female C3H/He mice with a low virulent T. cruzi clone. In this model,
      mating, fertilization, pregnancy evolution and delivery was carried out
      successfully. The offspring was infected at four, six and eighth weeks of age.
      The results showed that the offspring born to chagasic mothers present decreased
      resistance to acquired T. cruzi infection. This decreased resistance was
      expressed by higher levels of parasitaemia and higher mortality rates in
      offspring born to chagasic mothers than in controls. Age and sex were shown to be
      important factors of this phenomenon. The results suggest that maternal immune
      system products can modulate the immune response of the offspring.

PMID- 8736094
TI  - Trypanosoma cruzi strains and autonomic nervous system pathology in experimental
      Chagas disease.
AB  - Lesions involving the sympathetic (para-vertebral ganglia) and para-sympathetic
      ganglia of intestines (Auerbach plexus) and heart (right atrial ganglia) were
      comparatively analyzed in mice infected with either of three different strain
      types of Trypanosoma cruzi, during acute and chronic infection, in an attempt to
      understand the influence of parasite strain in causing autonomic nervous system
      pathology. Ganglionar involvement with neuronal destruction appeared related to
      inflammation, which most of the times extended from neighboring adipose and
      cardiac, smooth and striated muscular tissues. Intraganglionic parasitism was
      exceptional. Inflammation involving peripheral nervous tissue exhibited a focal
      character and its variability in the several groups examined appeared
      unpredictable. Although lesions were generally more severe with the Y strain,
      comparative qualitative study did not allow the conclusion, under the present
      experimental conditions, that one strain was more pathogenic to the autonomic
      nervous system than others. No special tropism of the parasites from any strain
      toward autonomic ganglia was disclosed.

PMID- 8736095
TI  - Tumor necrosis factor-alpha in human american tegumentary leishmaniasis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a cytokine produced by activated
      macrophages and other cells. In order to verify whether the serum levels of TNF
      alpha in American tegumentary leishmaniasis patients are associated with the
      process of cure or aggravation of the disease, 41 patients were studied: 26 cases
      of cutaneous leishmaniasis (CL) and 15 of mucocutaneous leishmaniasis (MCL).
      During active disease the serum levels of TNF-alpha of MCL patients were
      significantly higher than those of CL patients and control subjects (healthy
      individuals and cutaneous lesions from other etiologies). The MCL patients had
      serum titers of TNF-alpha significantly lower at the end of antimonial therapy
      than before therapy. After a six-month follow-up, the MCL patients had serum
      levels of TNF-alpha similar to those observed at the end of the therapy as well
      as to those of CL patients and control subjects. No significant variation in the
      serum levels of TNF-alpha was observed in CL patients throughout the study period
      (before, at the end of therapy and after a six-month follow-up). The possible
      relationship between the high TNF-alpha serum levels and severity of the disease
      is discussed.

PMID- 8736097
TI  - Reproductive behavior of Ravinia belforti (Prado & Fonseca, 1932) (Diptera:
      Sarcophagidae) females reared, in isolation, in the laboratory at Rio de Janeiro,
      RJ, Brazil.

PMID- 8736098
TI  - Comparison of the blood meal size among Triatoma infestans, T. guasayana and T.
      sordida (Hemiptera: Reduviidae) of Argentina under laboratory conditions.

PMID- 8736096
TI  - Biochemical, immunological and toxicological characteristics of the crystal
      proteins of Bacillus thuringiensis subsp. medellin.
AB  - Characterization of the insecticidal and hemolytic activity of solubilized
      crystal proteins of Bacillus thuringiensis (Bt) subsp. medellin (Btmed) was
      performed and compared to solubilized crystal proteins of isolates 1884 of B.
      thuringiensis subsp. israelensis (Bti) and isolate PG-14 of B. thuringiensis
      subsp. morrisoni (Btm). In general, at acid pH values solubilization of the Bt
      crystalline parasporal inclusions (CPI) was lower than at alkaline pH. The
      larvicidal activity demonstrated by the CPI of Btmed indicated that optimal
      solubilization of CPI takes place at a pH value of 11.3, in Bti at pH values from
      5.03 to 11.3 and in Btm at pH values from 9.05 to 11.3 Hemolytic activity against
      sheep red blood cells was mainly found following extraction at pH 11.3 in all Bt
      strains tested. Polyacrylamide gel electrophoresis under denaturing conditions
      revealed that optimal solubilization of the CPI in all Bt strains takes place at
      the alkaline pH values from 9.05 to 11.3. An enriched preparation of Btmed
      crystals was obtained, solubilized and crystal proteins were separated on a size
      exclusion column (Sephacryl S-200). Three main protein peaks were observed on the
      chromatogram. The first peak had two main proteins that migrate between 90 to 100
      kDa. These proteins are apparently not common to other Bt strains isolated to
      date. The second and third peaks obtained from the size exclusion column yielded
      polypeptides of 68 and 28-30 kDa, respectively. Each peak independently, showed
      toxicity against 1st instar Culex quinquefasciatus larvae. Interestingly,
      combinations of the fractions corresponding to the 68 and 30 kDa protein showed
      an increased toxicity. These results suggest that the 94 kDa protein is an
      important component of the Btmed toxins with the highest potency to kill mosquito
      larvae. When crystal proteins of Bti were probed with antisera raised
      independently against the three main protein fractions of Btmed, the only crystal
      protein that showed cross reaction was the 28 kDa protein. These data suggest
      that Btmed could be an alternative bacterium for mosquito control programs in
      case mosquito larval resistance emerges to Bti toxic proteins.

PMID- 8736099
TI  - The effect of different proportions of males and females over the Chrysomya
      albiceps (Wiedemann 1819) (Diptera, calliphoridae) biotic potential and longevity
      under laboratory conditions.
AB  - Chrysomya albiceps specimens were derived from colonies kept under laboratory
      conditions. The oviposition period, total number of eggs-mass and the weight of
      the eggs-mass (average/female) presented significant differences between colonies
      regarding the sexual ratio of 1 male/1 female (situation 1), when compared to the
      other ratios (1 male/3 female, situation II), (1 male/5 female, situation III),
      (3 male/1 female, situation IV) and (5 male/1 female, situation V). It was
      ascertained that the increase in the proportion of females, resulted in higher
      weight and greater number of ovipositions and lengthening of the period of
      oviposition, leads to a decrease in their lifespan.

PMID- 8736100
TI  - [Bionomical aspects of the Squamatoides triviattus (Diptera, Sarcophagidae) under
      laboratory conditions].
AB  - Experiments with Squamatoides trivitattus were carried out in two different
      controlled temperatures (16 +/- 1 degree C/50-60% RH and 27 +/- 1 degree C/70-80%
      RH). The viability of larvae and pupae at 27 degrees C was 89.82% and 92.75%
      respectively. Larvae did not develop at 16 degrees C. Larval development lasted
      for 20 +/- 4 hr, 16 +/- 8 hr and 60 +/- 7 hr for the first, second and third
      instars, respectively, completing a total of 96 +/- 6 hr. The mean pupal period
      lasted for 15.7 +/- 1.6 days. In longevity tables for the adults, life-expectancy
      for 50% of the colony submitted to 16 degrees C was of 1.78 weeks for males and
      2.42 for females. At 27 degrees C a life-expectancy of 1.15 weeks for males and
      0.78 week for females was recorded. The average life-spans for males and females
      at 16 degrees C were 3.5 +/- 2.0 and 3.8 +/- 2.6 weeks, respectively, and 1.9 +/-
      1.2 weeks for both sexes. At 27 degrees C, the longevity recorded was of 2.1 +/-
      1.3 weeks for males and 1.7 +/- 1.1 week for females.

PMID- 8736101
TI  - Ultrastructural aspects of the replication of dengue virus type 2 isolated in
      Brazil.

PMID- 8736102
TI  - Theoretical estimates of consumable food and probability of acquiring food in
      larvae of Chrysomya putoria (Diptera: Calliphoridae).
AB  - An indirect estimate of consumable food and probability of acquiring food in a
      blowfly species, Chrysomya putoria, is presented. This alternative procedure
      combines three distinct models to estimate consumable food in the context of the
      exploitative competition experienced by immature individuals in blowfly
      populations. The relevant parameters are derived from data for pupal weight and
      survival and estimates of density-independent larval mortality in twenty
      different larval densities. As part of this procedure, the probability of
      acquiring food per unit of time and the time taken to exhaust the food supply are
      also calculated. The procedure employed here may be valuable for estimations in
      insects whose immature stages develop inside the food substrate, where it is
      difficult to partial out confounding effects such as separation of faeces. This
      procedure also has the advantage of taking into account the population dynamics
      of immatures living under crowded conditions, which are particularly
      characteristic of blowflies and other insects as well.

PMID- 8736103
TI  - Beyond maps: a dynamic view of the somatosensory system.
AB  - Current theories on how tactile information is processed by the mammalian
      somatosensory system are based primarily on data obtained in studies in which the
      physiological properties of single neurons were characterized, one at a time, in
      behaving or anesthetized animals. Yet, the central nervous system relies on the
      concurrent activation of large populations of neurons to process the variety of
      sensory stimuli that contribute to normal tactile perception. The recent
      introduction of electrophysiological methods for chronic and simultaneous
      recordings of the extracellular activity of large numbers of single neurons per
      animal has allowed us to investigate, for the first time, how populations of
      neurons, located at multiple processing stages of the somatosensory system,
      interact following passive and active tactile stimulation. The rat trigeminal
      somatosensory system was used as a model for this investigation. Our results
      revealed the existence of highly dynamic and distributed representations of
      tactile information, not only in the somatosensory cortex, but also in the
      thalamus and even in the brainstem. In these structures, we identified broadly
      tuned neurons with multiwhisker receptive fields (RFs). In the thalamus, a large
      percentage of neurons exhibited shifts in the spatial domain of their RFs as a
      function of post-stimulus time. During these shifts, the center of the neuron's
      RF moved across the whisker pad from caudal to rostral whiskers, but not in the
      opposite direction, suggesting that these spatiotemporal RFs may encode
      directional information. Further studies revealed that somatosensory
      representations were maintained by dynamic interactions between multiple
      convergent afferents, since they could be altered in a matter of seconds by
      reversible sensory deprivations. Overall, these results suggest that the rat
      somatosensory system relies on both spatial and temporal interactions between
      populations of cortical and subcortical neurons to process multiple attributes of
      tactile stimuli.

PMID- 8736104
TI  - Protein targeting to the plant vacuole--a historical perspective.
AB  - Although many properties of the targeting of plant endomembrane proteins are
      similar to mammalian and yeast systems, several clear differences are found that
      will be stressed in this review. In the past few years, we have seen an
      advancement in our understanding of the signals for vacuolar protein targeting
      and some insights into the mechanisms of transport to the vacuole in the plant
      cell. This work will form the basis for elucidation of the fundamental principles
      that govern protein trafficking through the secretory system to the vacuole.

PMID- 8736105
TI  - Malaria diagnosis: a review.
AB  - Malaria is the most prevalent endemic disease in large parts of the world and is
      subject to control by health authorities. Today, the goal of malaria control is
      to prevent mortality and reduce morbidity and socioeconomic losses through the
      progressive improvement and strengthening of local and national capabilities. The
      World Health Organization considers early diagnosis as the first basic element of
      the strategy to control the disease. Traditionally, laboratory diagnosis has been
      made using the thick blood film, which continues to be the gold standard test.
      However, this test has disadvantages such as the manner in which the film is
      prepared, the level of training of the observer, the adequacy of maintenance of
      materials and equipment and its only fair sensitivity. Thus, many research
      laboratories have concentrated their efforts on the development of alternative
      methods for malaria diagnosis. These include methods for the detection of
      Plasmodia within erythrocytes (fluorescent microscopy, Quantitative Buffy Coat
      (QBC), dark field microscopy, nucleic acid probes and immunofluorescence),
      methods for the detection of plasmodial antigens in body fluids
      (radioimmunoassay, enzyme immunoassay) and methods for the detection of anti
      plasmodial antibodies in serum (indirect immunofluorescence, enzyme immunoassay,
      Western blotting). Here, we critically review the various methods for malaria
      diagnosis based on the world's literature and our experience with most of them,
      with emphasis on recent advances.

PMID- 8736106
TI  - Fatty acid oxidation in lymphocytes from Walker 256 tumor-bearing rats.
AB  - The oxidation of fatty acids in lymphocytes from the mesenteric lymph nodes of
      Walker 256 carcinosarcoma-bearing rats (TB) was studied, as well as the activity
      of the mitochondrial long-chain fatty acid transport system. Two-month old Wistar
      rats were subcutaneously implanted with 10(7) cells and after 2 weeks the tumor
      mass was 15-20% of the carcass weight. The activity of carnitine
      palmitoyltransferase (CPT) II was demonstrable in the lymphocytes of the TB group
      (8.2 +/- 5.6 nmol/min per mg mitochondria protein for 15 rats) and was not
      detected in the control, while that of CPT I was only slightly increased in the
      former. Similar rates of [1-14C]-palmitate decarboxylation were found for TB and
      control rat lymphocytes. However, when the rate of decarboxylation of [1-14C]
      palmitate present in the intracellular pool of lipids was investigated in
      cultured lymphocytes, the cells of TB rats exhibited rates 17-fold higher than
      those of control animals in the presence of fetal calf serum (FCS).
      Decarboxylation in the presence of TB rat serum was 178-fold higher than obtained
      with normal rat serum, and 1.4-fold compared to FCS. These results suggest that,
      during cachexia, lymphocytes preferably oxidize intracellular lipids, and that
      this capacity is greatly enhanced by factors circulating in the serum of tumor
      bearing rats.

PMID- 8736107
TI  - Validation of a Portuguese version of the Beck Depression Inventory and the State
      Trait Anxiety Inventory in Brazilian subjects.
AB  - We have validated a Portuguese version of the Beck Depression Inventory (BDI) and
      State-Trait Anxiety Inventory (STAI) tests by obtaining profiles for three
      Brazilian samples: 270 university students, 117 panic patients and 30 depressed
      patients. The mean BDI scores were higher for depressed patients (25.2 +/- 12.6),
      intermediate for anxious patients (15.8 +/- 10.3) and lower for students (8.5 +/-
      7.0). Mean STAI scores for anxious (52.8 +/- 11.4) and depressed patients (56.4
      +/- 10.5) were higher than for the student sample (40.7 +/- 8.6). BDI and STAI
      scores were correlated significantly in all samples. The internal consistency of
      the Portuguese version of BDI is in agreement with the literature (0.81 for
      students and 0.88 for depressed patients). The present data demonstrate that the
      psychometric properties of the Portuguese versions of the BDI and STAI are
      comparable to the original English language versions of these questionnaires,
      thereby indicating their use in clinical situations.

PMID- 8736108
TI  - Effect of improved glycemic control on blood pressure and albuminuria of insulin
      dependent diabetes without nephropathy.
AB  - To assess the effect of glycemic control on blood pressure (BP) and albumin
      excretion rate (AER) in insulin-dependent diabetes, 35 patients (age 12.6 +/- 2.7
      years) and 45 matched control subjects (11.9 +/- 1.8 years) were studied at an
      educational camp (Study I). They were evaluated at the beginning and at the end
      of a 9-day program of adequate diet and exercise twice daily, which induced
      statistically significant reductions in urinary glucose (18 +/- 21 to 5 +/- 7
      g/12 h, P < 0.01) and in insulin requirement (42 +/- 20 to 31 +/- 12 U/day, P <
      0.01) in the diabetic group. The mean BP and AER of the diabetic patients fell
      from 74 +/- 11 to 69 +/- 11 mmHg, P < 0.001, and from 4.9 +/- 6.0 to 2.1 +/- 2.0
      micrograms/min, P < 0.01, and a correlation was found between AER and urinary
      glucose. In contrast, controls showed a lower reduction in BP and no change in
      AER. To evaluate the mechanisms involved in BP fall another group of 39 diabetics
      (age 12.7 +/- 2.1 years) was submitted to the same 9-day program and also to
      improved glycemic control (Study II). Changes in BP (79 +/- 11 to 76 +/- 11 mmHg,
      P < 0.05) were slighter than in the previous study. Initial creatinine clearance
      was high and fell to the normal range at the end of the study (159 +/- 99 to 127
      +/- 42 ml min-1 (1.73 m2)-1, P < 0.05). Urinary aldosterone decreased from 5.3 +/
      3.9 to 3.4 +/- 2.4 micrograms/24 h (P < 0.05), and fractional Na+ excretion
      tended to increase. Initial and final metanephrine values did not differ. Changes
      in mean BP did not correlate with changes in aldosterone, insulin requirement or
      urinary glucose. The decreases in hyperfiltration and AER may have been due to
      the improved glycemic control induced by this educational program. Exercise may
      be responsible for BP reduction in diabetics and controls. BP changes
      particularly in diabetics could be attributed to the inhibition of the renin
      angiotensin-aldosterone system and/or to decreased insulin requirement. The
      contribution of a negative Na+ balance consequent to decreased plasma insulin
      levels to the BP fall cannot be excluded.

PMID- 8736109
TI  - Sensitivity of vincristine-sensitive K562 and vincristine-resistant K562-Lucena 1
      cells to anthracyclines and reversal of multidrug resistance.
AB  - The phenomenon of multidrug resistance (MDR), that involves the efflux pump P
      glycoprotein, can be reversed by a number of substances known as MDR modulators
      or reversing agents. In the present study we investigated the action of three
      anthracyclines, mitoxantrone and vincristine on short-term (72 h) cultures using
      2 methods ([3H] incorporation and MTT (3-[4,5-dimethylthiasol-2-yl]-2,5
      diphenyltetrazolium bromide)), on 2 cell lines: K562, a human erythroleukemia,
      and a vincristine-resistant subline K562-Lucena 1. Using the same culture methods
      plus flow cytometry analysis, the reversing potentials of cyclosporin A and
      verapamil were studied in both cell lines. There were differences in the
      sensitivity and resistance profiles of the two lines to the various drugs but
      daunorubicin (5 micrograms/ml) and idarubicin (0.035 micrograms/ml) were the most
      effective when each was used in high concentration. Cyclosporine at 200 ng/ml and
      verapamil at 5 micrograms/ml reversed MDR in the resistant line, and had a
      synergistic action with chemotherapeutic agents on the sensitive line. Again
      differences were demonstrable between combinations of the various drugs and
      reversal was only clearly shown with the method measuring cell proliferation
      ([3H] incorporation) but not by the method measuring metabolic activity (MTT).
      The efflux of rhodamine-123 mimics the functional activity of the pump and
      cyclosporine was a better reversing agent by this criteria. These data show that
      the results obtained in in vitro studies attempting to identify treatments for
      different types of leukemias depend to a large extent on the methods used to
      measure cell response.

PMID- 8736110
TI  - Natural killer cells and interleukin-12 in patients with advanced cervical cancer
      under neoadjuvant chemotherapy.
AB  - Patients with advanced cervical cancer have deficient natural killer (NK) cell
      activity, usually as a consequence of tumor invasion, which results in tumor NK
      cell sequestration. The reason for the occurrence of such alterations in patients
      under chemotherapy is unknown. We evaluated the activity and number of NK cells
      and T cell subpopulations in ten patients before and three weeks after
      neoadjuvant chemotherapy (CT). The schedule used was cis-platinum (100 mg/m2 per
      cycle) and bleomycin (15 mg/cycle), repeated every 28 days. Although there were
      similar levels of NK cells before and after CT in both groups, we observed
      greater cytotoxicity of peripheral blood lymphocytes and increased levels of CD4+
      and CD8+ T cells (P < 0.01) in five patients who presented a good clinical
      response when compared to the group with a poor response. IL-12, known to
      increase NK cell activity when added to peripheral blood lymphocyte cultures,
      markedly increased lytic activity before and after CT only in the group with a
      good clinical response. These results suggest that NK cells from the poorly
      responding patient group express less lytic activity per NK cell and are
      insensitive to IL-12 stimulation, probably as a result of reduced IL-12 receptor
      expression or a defective intracellular transduction mechanism. The present
      findings may be useful as a prognostic factor in clinical practice and also
      provide support for human clinical trials of IL-12 and neoadjuvant CT for the
      treatment of malignant cervical tumors.

PMID- 8736111
TI  - Trifluoperazine reduces the expression of CD69 in phytohemagglutinin-activated
      lymphocytes.
AB  - Trifluoperazine (TFP) is a phenothiazine capable of inhibiting lymphocyte
      proliferation as well as natural killer cells (NK) and lymphokine-activated
      killer cells (LAK) cytotoxic activity. CD69 is a surface molecule induced by
      various mechanisms of cellular activation. In the present work the modulation of
      CD69 expression by TFP was investigated on PHA-stimulated peripheral blood
      mononuclear cells and compared to that of CD25 (IL-2 receptor) expression.
      Determination of surface molecules was performed in an indirect
      immunofluorescence assay using anti-CD69 or anti-CD25 monoclonal antibodies, and
      analyzed by flow cytometry. The time course of the expression of these two
      molecules differed: CD69 expression was already declining at 48 h, whereas CD25
      was still increasing at 72 h after stimulation. TFP (10 microM) reduced CD69
      expression by 71.8% at 24 h, 68.4% at 48 h and 24% at 72 h following activation.
      In contrast, the same dose of TFP did not significantly affect CD25 expression at
      24 h but showed an inhibitory effect at later times. These results suggest that
      different activation pathways are involved in the expression of CD25 and CD69.

PMID- 8736112
TI  - In vitro induced antibody production for the diagnosis of herpes simplex virus
      infection in immunosuppressed patients.
AB  - We developed and evaluated a specific test for herpes simplex virus (HSV)
      infection based on the secretion of HSV-specific antibodies by lymphocytes
      stimulated in vitro with HSV-1 antigens. The in vitro induced antibody production
      (IVIAP) test was used for the diagnosis of HSV infection in 43 seropositive
      selected subjects: 9 healthy subjects (controls), 30 symptomatic patients (26 of
      them immunocompromised and 4 immunocompetent) and 4 patients with varicella
      zoster infection. Anti-HSV antibodies were detected by an immune assay using an
      anti-human IgG peroxidase conjugate. The test showed a sensitivity of 93% (15/16)
      and specificity of 92% (1/13) which were confirmed by positive culture or
      clinical and laboratory follow-up. One AIDS patient had a false-negative result
      and one false-positive result (1/9) was obtained among the healthy subjects. All
      patients infected with varicella zoster virus were negative to the IVIAP test.
      The test is rapid, inexpensive, easy to interpret and can be used for the
      diagnosis of HSV infections, especially in immunocompromised patients.

PMID- 8736113
TI  - Anticardiolipin antibodies from syphilis and systemic lupus erythematosus induce
      leakage in cardiolipin vesicles.
AB  - Anticardiolipin antibodies from sera of patients with systemic lupus
      erythematosus or syphilis induced leakage of entrapped carboxyfluorescein (CF)
      from cardiolipin (CL)/phosphatidylcholine(PC) vesicles prepared by sonication of
      equimolar mixtures of CL:PC. The sera dilution used here was 1:7500. IgG (5-20
      micrograms/ml) from the same sera, not containing beta 2GPI, also produced a
      concentration-dependent leak. Vesicle leakage was inhibited by salt and was not
      detected with vesicles prepared exclusively with phosphatidylcholine. The
      demonstration of antibody-induced vesicle leakage offers a convenient system to
      investigate the mechanism of antibody-lipid binding as well as a potential
      diagnostic tool.

PMID- 8736114
TI  - Reinforcing properties of the substance P C-fragment analog DiMe-C7 in Carassius
      auratus.
AB  - The aim of the present study was to investigate whether two substance P (SP)
      fragments have reinforcing effects in Carassius auratus when the fish were tested
      in a place-preference experimental model. Fish were placed in a 3-compartment box
      in which one compartment gives access to two others that are not connected. The
      time spent in each compartment was recorded for 10 min in order to determine
      which one was preferred. Twenty-four hours later the fish were given one of the
      following ip treatments: 1) group VEH (N = 12), injected with teleost saline, 2)
      group DiMe-C7 (N = 12), injected with 33 micrograms/kg DiMe-C7, and 3) group SP1
      7 (N = 12), injected with 167 micrograms/kg SP1-7. Immediately after treatment
      the fish were kept for 30 min in the compartment that was the least preferred on
      the day before and this procedure was repeated for 3 days. On the fifth day the
      fish were retested for 10 min to determine the time spent in each compartment.
      Two-way analysis of variance with treatments and testing as factors indicated a
      main effect (P < 0.0025) as well as a testing effect (P < 0.009). The post-hoc
      Scheffe multiple comparison test indicated that only the DiMe-C7 group presented
      an increase in the time spent in the paired compartment after treatment. We
      suggest that the C-terminal fragment of SP has reinforcing effects in Carassius
      auratus.

PMID- 8736115
TI  - Intraventricular cycloheximide attenuates the restraint-induced long-lasting
      effect on plus maze exploration.
AB  - Rats submitted to 2 h of restraint stress show reduced open arm exploration in
      the elevated plus maze 24 h later. To determine if this effect is dependent on
      protein synthesis during or after the restraint period, cycloheximide, a protein
      synthesis inhibitor, was injected into the right cerebral ventricle of male
      Wistar rats (200-250 g), immediately before (N = 19 animals per group),
      immediately after (N = 7 animals per group) or 2 h (N = 10 animals per group)
      following a 2-h period of forced restraint. Twenty-four hours later the animals
      were tested in the elevated plus maze. Non-stressed control groups received
      saline (SAL, N = 8-9 per group) or cycloheximide (CHX, N = 8-9 per group) and
      were tested 1 h or 24 h later in the maze. Pre- but not post-stress
      microinjections of cycloheximide (20 micrograms in 2 microliters) increased
      exploration in the elevated plus maze (% of time spent in open arms, pre-stress
      injection: SAL = 4.6 +/- 1.2, CHX = 10.7 +/- 2.3; number of enclosed arms
      entries: SAL = 3.6 +/- 0.5, CHX = 5.6 +/- 0.4). No drug effect was observed in
      non-stressed animals. These results suggest that blockade of protein synthesis
      during the restraint period may attenuate the behavioral consequences of stress.

PMID- 8736116
TI  - Inhibitory effect of DUP-753 on the drinking responses of rats to central
      administration of noradrenaline and angiotensin II and to dehydration.
AB  - We investigated the effect of losartan (DUP-753) on the dipsogenic responses
      produced by intracerebroventricular (icv) injection of noradrenaline (40
      nmol/microliters) and angiotensin II (ANG II) (2 ng/microliters) in male Holtzman
      rats weighing 250-300 g. The effect of DUP-753 was also studied in animals
      submitted to water deprivation for 30 h. After control injections of isotonic
      saline (0.15 M NaCl, 1 microliter) into the lateral ventricle (LV) the water
      intake was 0.2 +/- 0.01 ml/h. DUP-753 (50 nmol/microliters) when injected alone
      into the LV of satiated animals had no significant effect on drinking (0.4 +/-
      0.02 ml/h) (N = 8). DUP-753 (50 nmol/microliters) injected into the LV prior to
      noradrenaline reduced the water intake from 2.4 +/- 0.8 to 0.8 +/- 0.2 ml/h (N =
      8). The water intake induced by injection of ANG II and water deprivation was
      also reduced from 9.2 +/- 1.4 and 12.7 +/- 1.4 ml/h to 0.8 +/- 0.2 and 1.7 +/-
      0.3 ml/h (N = 6 and N = 8), respectively. These data indicate a correlation
      between noradrenergic pathways and angiotensinergic receptors and lead us to
      conclude that noradrenaline-induced water intake may be due to the release of ANG
      II by the brain. The finding that water intake was reduced by DUP-753 in water
      deprived animals suggests that dehydration releases ANG II, and that AT1
      receptors of the brain play an important role in the regulation of water intake
      induced by deprivation.

PMID- 8736117
TI  - Losartan (DUP-753) blocks the natriuretic, kaliuretic and antidiuretic effect of
      intracerebroventricular injection of carbachol in water-loaded rats.
AB  - We determined the effect of intracerebroventricular (icv) administration of
      losartan, an angiotensin II (ANG II) subtype 1 receptor (AT1) antagonist, on icv
      carbachol-induced natriuresis, kaliuresis and antidiuresis in water-loaded male
      Holtzman rats (250-300 g) with a cannula implanted into the lateral ventricle
      (LV). The rats were water loaded with 5% of their body weight by gavage twice,
      with the second gavage one hour after the first. Carbachol (2 nmol in 1
      microliter) was injected icv immediately after the second load. When losartan
      (DUP-753, 50 nmol in 1 microliter) was administered icv, it was given 3 min
      before carbachol. Previous icv treatment with losartan significantly reduced the
      icv carbachol-induced natriuresis (324 +/- 17 microEq/120 min), kaliuresis (103
      +/- 15 microEq/120 min) and antidiuresis (13.5 +/- 2.1 ml/120 min) compared to
      the effects of previous icv injection of saline (Na+ excretion = 498 +/- 22
      microEq/120 min; K+ excretion = 167 +/- 20 microEq/120 min; urine volume = 5.2 +/
      1.2 ml/120 min). These results, reported as means +/- SEM for 12 rats in each
      group, are consistent with the hypothesis that AT1 subtype receptors participate
      in the regulation of body electrolyte balance.

PMID- 8736118
TI  - Noise and the quality of sleep in two hospitals in the city of Belo Horizonte,
      Brazil.
AB  - Male patients of two hospitals in Belo Horizonte completed a questionnaire during
      an interview on the day of discharge in order to evaluate sleeping conditions
      related to noise during the previous night and were retested 24 h later. Patients
      had a worse perception of sleep at the noisier hospital, the University Hospital
      of the Federal University of Minas Gerais (N = 13), whose internal mean nocturnal
      noise level was Leq = 53.7 db(A), than at the quieter hospital, Baleia (N = 22),
      whose internal mean nocturnal noise level was Leq = 45.5 db(A). Noise was the
      only sleep-disturbing factor which was statistically significant.

PMID- 8736119
TI  - Effect of estrogen and neuroleptics on prolactin secretion and immunoreactive
      prolactin cells.
AB  - The use of estrogen and dopamine receptor antagonists is associated with elevated
      prolactin levels and, in rats, chronic estrogen treatment is also associated with
      lactotroph proliferation. In this study, haloperidol, fluphenazine, sulpiride and
      metoclopramide, alone or combined with estradiol, were administered to Wistar
      rats. Pituitary weight, serum prolactin levels and percent of immunoreactive
      prolactin cells in the anterior pituitary glands were determined at the end of 60
      days of treatment. The pituitary weight of rats treated with estrogen alone or in
      combination with other drugs was significantly higher than the control group. The
      serum prolactin level was higher than the upper confidence limit in all but three
      of the 90 treated rats. While in the control group the percent of immunoreactive
      prolactin cells was 20%, administration of the neuroleptic drugs and
      metoclopramide increased this percent to approximately 30%, and estrogen alone or
      in combination with one of the neuroleptic drugs increased it to approximately
      40%. The results presented here demonstrate the relationship between prolactin
      secretion and prolactin cell number when different neuroleptics and related drugs
      are used.

PMID- 8736120
TI  - Evidence for neuronal release of isotopically labelled glycine from the rat
      ventral medullary surface in vivo.
AB  - Spontaneous and stimulus-induced release of isotopically labelled glycine was
      studied in the superfused rat dorsal or ventral medullary surface in vivo.
      Superfusion of the ventral medullary surface of anesthetized (urethane, 1.2 g/kg,
      ip) male adult Wistar rats (250-350 g) with high K+ (40 mM) surrogate
      cerebrospinal fluid (CSF) produced an average increase of 45% over the
      spontaneous efflux of exogeneously applied glycine (N = 5, P < 0.01). In
      experiments in which the calcium of the CSF was replaced by an equimolar amount
      of magnesium, the increase in glycine efflux in response to high K+ was reduced
      to 15%, a value not statistically different from that observed in control
      experiments (N = 6). Veratridine stimulation evoked a large (80%) increase in
      glycine efflux (N = 5, P < 0.001), which was inhibited by tetrodotoxin. High
      potassium or veratridine failed to modify spontaneous release of glycine on the
      dorsal medullary surface. Results obtained in control experiments showed that
      neither high K+ nor veratridine is effective in modifying spontaneous efflux of
      [3H]-leucine or [3H]-inulin on the ventral or dorsal medullary surface. These
      data support the hypothesis that glycine is a neurotransmitter on the ventral
      medullary surface and that it may be part of neural pathways involved in
      cardiorespiratory regulation present in this region.

PMID- 8736121
TI  - Pressor effects elicited by stimulation within the medullary raphe nuclei of the
      golden hamster (Mesocricetus auratus).
AB  - The medullary raphe nuclei are involved in central autonomic regulation. In all
      species investigated, electrical stimulation of the raphe nuclei causes
      cardiovascular responses, although these changes vary between species. The
      present study was designed to investigate the participation of these nuclei in
      cardiovascular regulation in the hamster. We studied the effect on arterial blood
      pressure (BP) and heart rate (HR) of electrical stimulation (isolated cathodal
      square wave pulses for 10 sec at 100 Hz, 40-100 microA and 1-msec pulse duration)
      within the medullary raphe nuclei in urethane-anesthetized (1.2 g/kg, iv, after
      ether induction) golden hamsters (Mesocricetus auratus, 130 to 150 g, either
      sex). Electrical stimulation of the same sites was performed on a group of
      paralyzed (Flaxedil, 1 mg/kg, iv) and artificially ventilated animals.
      Stimulation sites were histologically defined and maps of the stimuli were
      obtained for the effect of electrical stimulation on arterial blood pressure. In
      another series of experiments L-glutamate (0.18 M) was microinjected (75 to 150
      nl) into the nucleus raphe obscurus. Electrical stimulation of the raphe nuclei
      produced predominantly pressor responses (delta = +12 to +100 mmHg; 49.3% of the
      stimulated sites). Hypotension (delta = -5 to -20 mmHg; 14.6% of the stimulated
      sites) and no change in BP (35.3%) were evoked from fewer stimulation sites.
      Pressor responses were also predominant in paralyzed animals (delta = +15 to +95
      mmHg; 62.5% of the stimulated sites), and after microinjection of L-glutamate
      into the raphe obscurus (delta = +35 to +135 mmHg). The present results
      demonstrate that in the hamster the stimulation of these nuclei evokes mainly
      pressor responses. These responses are similar to those obtained in the rat and
      guinea pig but opposite to those observed in the cat and rabbit.

PMID- 8736122
TI  - Biochemistry below 0 degrees C: nature's frozen vertebrates.
AB  - Although alien to man, the ability to endure the freezing of extracellular body
      fluids during the winter has developed in several species of terrestrially
      hibernating frogs and turtles as well as in many species of insects and other
      invertebrates. Wood frogs, for example, can endure freezing for at least 2 weeks
      with no breathing, no heart beat or blood circulation, and with up to 65% of
      their total body water as ice. Our studies are providing a comprehensive view of
      the requirements for natural freezing survival and of the physical and metabolic
      protection that must be offered for effective cryopreservation of vertebrate
      organs. Molecular mechanisms of natural freeze tolerance in lower vertebrates
      include: 1) control over ice crystal growth in plasma by ice nucleating proteins,
      2) the accumulation of low molecular weight cryoprotectants to minimize
      intracellular dehydration and stabilize macromolecular components, and 3) good
      ischemia tolerance by all organs that may include metabolic arrest mechanisms to
      reduce organ energy requirements while frozen. Cryomicroscopy of tissue slices
      and magnetic resonance imaging (MRI) of whole animals is revealing the natural
      mode of ice propagation through an organism. MRI has also revealed that thawing
      is non-uniform; core organs (with high cryoprotectant levels) melt first,
      facilitating the early resumption of heart beat and blood circulation. Studies of
      the production and actions of the natural cryoprotectant, glucose, in frogs have
      shown its importance in maintaining a critical minimum cell volume in frozen
      organs and new work on the metabolic effects of whole body dehydration in 3
      species of frogs has indicated that adaptations supporting freeze tolerance grew
      out of mechanisms that deal with desiccation resistance in amphibians. Studies of
      the regulation of cryoprotectant glucose synthesis by wood frog liver have shown
      the role of protein kinases and of alpha and beta adrenergic receptors in
      regulating the glycemic response, and of changes in membrane glucose transporter
      proteins to facilitate cryoprotectant distribution.

PMID- 8736123
TI  - Myosin-V: a class of unconventional molecular motors.
AB  - In this review we focus on the biochemical and structural properties of the
      myosin-V class of unconventional myosins as an example of the diversity of
      molecular motors within the myosin superfamily. A member of this class was first
      identified as a novel calmodulin-binding protein in mammalian brain (Larson RE,
      Pitta DE and Ferro JA (1988). Brazilian Journal of Medical and Biological
      Research, 21: 213-217). To date, the myosin-V class is represented by two
      molecules from yeast, one from nematodes, several from vertebrates (chickens,
      rats, mice and humans) and possibly one from plants. The domain structure of
      these myosins features a highly conserved head containing the ATP-hydrolysis and
      actin-binding sites, an extended neck composed of six tandem IQ-motifs which are
      sites for calmodulin binding and a large tail which has coiled-coil segments
      intercalated with globular regions of as yet unknown function. Biochemical
      studies on purified myosin-V from vertebrate brains and the description of myosin
      V mutants in yeast and mice have made myosin-V one of the best characterized,
      unconventional myosin classes at the present time, surpassed only by the well
      studied myosin-I class.

PMID- 8736124
TI  - Chitin-binding proteins from cowpea (Vigna unguiculata) seeds.
AB  - Vicilins (7S storage proteins) from cowpea (Vigna unguiculata) and other legume
      seeds were shown to bind to chitin, to regenerated chitin (fully acetylated
      chitin) and to chitosan (deacetylated chitin). Adsorbed vicilins were desorbed
      from these matrices by acetic and hydrochloric acids and by highly polymerized
      soluble chitosan. Proteins such as the lectin of common bean (PHA), soybean
      trypsin inhibitor (Kunitz), a beta-1,3-glucanase from cowpea seeds, bovine
      pancreatic alpha-chymotrypsin, chicken ovalbumin, serum albumin and rabbit gamma
      globulin did not bind. The present result is the first description of vicilin
      binding to chitin but other proteins, such as wheat germ agglutinin (WGA), a
      lectin that contains the so called "chitin-binding domain", and a chitinase
      isolated from cowpea seeds, which are involved in the defense mechanisms of
      plants against insects and fungi, were also shown to bind to chitin as previously
      reported. The binding of vicilins to chitin is probably effected not through a
      "chitin-binding domain" because they do not share this sequence with the defense
      related proteins cited above. We propose that this association of vicilins with
      chitin may be related to the effect of variant vicilins on the development of
      Callosobruchus maculatus (bruchid) in resistant cowpea seeds.

PMID- 8736125
TI  - Kinetic characterization of rat tissue kallikrein using N alpha-substituted
      arginine 4-nitroanilides and N alpha-benzoyl-L-arginine ethyl ester as
      substrates.
AB  - Hydrolysis of seven N alpha-substituted L-arginine 4-nitroanilides: benzoyl
      arginine p-nitroanilide (Bz-Arg-Nan), tosyl-arginine p-nitroanilide (Tos-Arg
      Nan), acetyl-leucyl-arginine p-nitroanilide (Ac-Leu-Arg-Nan), acetyl-phenylalanyl
      arginine p-nitroanilide (Ac-Phe-Arg-Nan), benzoyl-phenylalanyl-arginine p
      nitroanilide (Bz-Phe-Arg-Nan), tosyl-phenylalanyl-arginine p-nitroanilide (Tos
      Phe-Arg-Nan), and D-valyl-leucyl-arginine p-nitroanilide (D-Val-Leu-Arg-Nan), and
      the N alpha-substituted L-arginine ester: benzoyl-arginine ethyl ester (Bz-Arg
      OEt), by rat tissue kallikrein was studied throughout a wide range of substrate
      concentrations. The enzyme showed a bimodal behavior with all the substrates
      tested except Tos-Arg-Nan. At low substrate concentrations (10 to 170 microM for
      p-nitroanilides and 50 to 190 microM for Bz-Arg-OEt) the hydrolysis followed
      Michaelis-Menten kinetics, but at higher substrate concentrations (150 to 700
      microM for p-nitroanilides and 200 to 1800 microM for Bz-Arg-OEt) a deviation
      from Michaelis-Menten kinetics was observed with a significant decrease in
      hydrolysis rates. At high concentrations of the p-nitroanilide substrates,
      partial enzyme inhibition was observed, whereas complete enzyme inhibition was
      observed with Bz-Arg-OEt at high concentration. The kinetic parameters reported
      here were calculated from data for substrate concentrations range where the
      enzyme followed Michaelis-Menten behavior. D-Val-Leu-Arg-Nan (Km = 24 +/- 2
      microM; Vmax = 10.42 +/- 0.28 microM/min) was the best substrate tested, followed
      by Ac-Phe-Arg-Nan (Km = 13 +/- 2 microM; Vmax = 3.21 +/- 0.11 microM/min), while
      Tos-Arg-Nan (Km = 29 +/- 2 microM; Vmax = 0.10 +/- 0.002 microM/min) was the
      worst of the tested substrates for rat tissue kallikrein. For the hydrolysis of
      Bz-Arg-OEt (Km = 125 +/- 15 microM; Vmax = 121.3 +/- 7.6 microM/min), the kinetic
      parameters using a substrate inhibition model can reasonably account for the
      observed enzyme behavior, with a Ksi value about 13.6 times larger than the
      estimated Km value.

PMID- 8736126
TI  - Turnover and shedding of the Tc-85 surface glycoprotein of Trypanosoma cruzi
      trypomastigotes.
AB  - Tc-85 is an 85-kDa surface glycoprotein specific for the trypomastigote stage of
      Trypanosoma cruzi which has been implicated in the invasion of host cells by the
      parasite. Tc-85 has a half-life of 3.5-4 h and is synthesized as a 95-kDa
      precursor. Processing of the 95-kDa precursor is inhibited by N-p-tosyl-L-lysine
      chloromethyl ketone, p-chloromercuriphenylsulfonic acid, iodoacetamide or N
      ethylmaleimide, but not by aprotinin, antipain or phenylmethylsulfonil fluoride.
      Tc-85, but not the precursor, is rapidly shed into the medium, allowing a
      correlation between the decrease of Tc-85 in trypomastigotes and its increase in
      the culture medium. The shedding of Tc-85 was inhibited 50% by 1 microM
      tunicamycin, but not by 10 microM swainsonine or 10 microM 1-deoxynojirimycin
      under the experimental conditions employed. This suggests that N-linked
      oligosaccharides are important for the shedding phenomenon, although it appears
      that they do not have to be fully processed for shedding to occur.

PMID- 8736127
TI  - Patterns of long-term steroidogenesis stimulation by ACTH and phorbol ester.
AB  - Adrenocorticotropic hormone (ACTH) triggers well-defined responses in Y-1 cells.
      Among them is steroidogenesis stimulation. We have previously shown that phorbol
      12-myristate 13-acetate (PMA), an activator of the calcium- and phospholipid
      dependent protein kinase (PKC) is able to mimic all the responses triggered by
      ACTH in these cells, including steroidogenesis stimulation. Short (2 h) treatment
      with PMA leads to only 20-30% of the maximal steroidogenesis stimulation obtained
      with ACTH. However, the steroid secretion in the 2 h that follows the short-term
      (2 h) PMA treatment reaches the same levels as observed with ACTH, i.e., a 12- to
      15-fold increase. We also show that this effect is restricted to cells treated
      with PMA for up to 4 h, while treatment for longer periods of time causes a
      reduction of the steroid biosynthesis rate, an effect that is not observed in
      cells treated with ACTH or N6,2'-0-dibutyryladenosine 3',5'-cyclic monophosphate
      (dcAMP). These results suggest that activation of PKC can elicit the first phase
      of ACTH steroidogenesis stimulation, but not the second one, which strictly
      depends on activation of cAMP-dependent protein kinase.

PMID- 8736128
TI  - Immobilization of xanthine oxidase on a polyaniline silicone support.
AB  - A polyaniline silicone support to immobilize xanthine oxidase is proposed as a
      reactor coil to monitor the action of xanthine oxidase on hypoxanthine, xanthine
      and 6-mercaptopurine. A purified xanthine oxidase immobilized on this support
      lost 80% of the initial activity after 12 min of use. Co-immobilization of
      superoxide dismutase and catalase increased the stability of immobilized xanthine
      oxidase so that the derivative maintained 79% of its initial activity after 4.6 h
      of continuous use in which 1.5 mumol purine bases were converted by the
      immobilized enzyme system. There is no evidence of either polyaniline or protein
      leaching from the coil during 3 h of continuous use. When solutions (10 ml) of
      hypoxanthine, xanthine and 6-mercaptopurine were circulated individually through
      the xanthine oxidase-superoxide dismutase-catalase-polyaniline coil (1 mm
      internal diameter and 3 m in length, 3 ml internal volume) activities of 8.12,
      11.17 and 1.09 nmol min-1 coil-1, respectively, were obtained. The advantages of
      the reactor configuration and the redox properties of the polymer, particularly
      with respect to immobilized oxidoreductases, make this methodology attractive for
      similar enzyme systems. This immobilized enzyme system using polyaniline-silicone
      as support converted 6-mercaptopurine to 6-thiouric acid with equal efficiency as
      resins based on polyacrylamide and polyamide 11.

PMID- 8736129
TI  - Frequency of pap and pil operons in Escherichia coli strains associated with
      urinary infections.
AB  - Strains of E. coli isolated from patients with urinary tract infection were
      examined for P and type 1 adhesin production by colony hybridization with pap and
      pil operons. The P pili probe detected 45 (46.4%) of the total of 97 strains
      studied and the type 1 pili probe detected 83 (85.6%). The pap operon was
      detected in 39 (53.4%) of 73 strains isolated from urine of patients with urinary
      disease and in 6 (25.0%) of 24 strains isolated from feces of healthy individuals
      employed as controls (P = 0.029), and the pil operon was detected in 67 (91.8%)
      of the urinary strains and in 16 (66.6%) of the fecal strains (P = 0.007). Our
      data did not show significant differences in frequency of P pili among isolates
      from pyelonephritis (78.5%), cystitis (45.8%) and asymptomatic bacteriuria
      (54.5%). Type 1 pili were not associated with the different types of infection;
      the frequency of these pili was 100% in pyelonephritis and in asymptomatic
      bacteriuria, and 87.5% in cystitis. The incidence of pap operon in strains
      isolated from pyelonephritis and from asymptomatic bacteriuria was higher in 11-
      to 40-year old women. These data show a high frequency of pap and pil operons
      among uropathogenic strains of E. coli, which seems to be an important factor in
      the development of urinary infection.

PMID- 8736130
TI  - Substance P does not modify mononuclear cell migration into Ehrlich tumor mass.
AB  - In the present study, seven adult male mice were inoculated with Ehrlich tumor
      into the footpad after local substance P release was blocked by neurectomy of the
      sciatic and saphenous nerves. The contralateral footpad was also inoculated but
      sham-operated, and used as control. This procedure did not modify the percent of
      CD4+ (about 1-2%), CD8+ (about 1-3%), macrophages (about 21-22%), lymphocyte B
      (about 0-1%) and NK (about 1-2%) mononuclear cells present among tumor cells.
      These data suggest that chemotactic activity of substance P may not be relevant
      in this situation because the lack of this neurotransmitter (checked by
      immunohistochemistry) secondary to neurectomy did not change the cell migration
      profile into tumor mass.

PMID- 8736131
TI  - Dietary sodium intake and cardiac nerve cell hypertrophy in Wistar rats.
AB  - We determined the effect of dietary sodium intake (0.15 and 8% NaCl) on the
      cardiac neuron size of normotensive 3-week old Wistar rats. An increase in
      dietary sodium for 48 weeks induced an increase in neuronal size. The number of
      large neurons (larger than 500 microns 2) increased significantly (chi-square
      test) in rats ingesting 8% NaCl in their food. The rats presented hypertension
      (128 +/- 9 vs 134 +/- 16 mmHg; difference not significant, Student t-test) and a
      statistically significant increase in cardiac muscle mass (1.6 +/- 0.1 vs 2.0 +/-
      0.2 mg/g of rat). We conclude that food sodium can significantly increase cardiac
      nerve cell size and this trophic response occurs concomitantly with an increase
      of cardiac muscle mass.

PMID- 8736132
TI  - Cytotoxic activity of a methanol extract of Phallusia nigra (Tunicata,
      Ascidiacea).
AB  - Tunicates have been reported to be a rich source of biologically active
      compounds. In this study, we demonstrate the presence of cytotoxic substances in
      Phallusia nigra, a common tunicate from Brazilian coastal waters. An extract of
      tunicate tissue was obtained by homogenizing the visceral organs from 50
      specimens in methanol, followed by filtration and concentration in a rotary
      vacuum evaporator. Finally, the concentrate was partitioned with chloroform to
      remove lipids. The resulting extract possessed antimitotic and hemolytic
      activity. The former was demonstrated as a delay in the development of sea urchin
      eggs by partially inhibiting the process of cleavage (first cleavage, EC50 +/-
      SEM = 3.44 +/- 0.84 mg/ml). The < 500 molecular fraction of the extract obtained
      by ultrafiltration also inhibited cell proliferation (the number of viable cells
      was decreased by 68% with 500 micrograms/ml) and DNA synthesis of T47D cells
      derived from human breast carcinoma as measured by [3H]-thymidine incorporation
      (66% of the control value after 24-h incubation with 100 micrograms/ml). Dose
      dependent hemolysis obtained with P. nigra extract on mouse erythrocytes had an
      EC50 +/- SEM = 1.12 +/- 0.02 mg/ml for a 0.5% erythrocyte suspension. Hemolysis
      could be reduced by pre-incubating the cells with choline-containing
      phospholipid. Sphingomyelin (40 micrograms/ml) increased the EC50 by two-fold to
      2.86 +/- 0.04 mg/ml, but phosphatidylcholine (80 micrograms/ml) did not modify
      hemolysis.

PMID- 8736133
TI  - Distinct grooming patterns induced by intracerebroventricular injection of CRH,
      TRH and LHRH in male rats.
AB  - This paper reports the effects on grooming, related behaviors and levels of
      anxiety induced by the hypophysiotropic peptides corticotropin-releasing hormone
      (CRH, 1 microgram, 0.2 nmol, icv), thyrotropin-releasing hormone (TRH, 100
      micrograms, 275 nmol, icv) and luteinizing hormone-releasing hormone (LHRH, 1.5
      micrograms, 1.3 nmol, icv) administered into the lateral ventricle of the brain
      (icv) of adult male rats of a Holtzman-derived colony (N = 15, each group). CRH
      induced an increase in total grooming scores, whereas LHRH, TRH and vehicle had
      no effect. CRH strongly increased face and head grooming and induced head shakes.
      The time spent in rearing and gnawing was significantly decreased. In the plus
      maze, CRH reduced the time of exploration in the open arm. TRH increased face
      grooming and induced body shakes. LHRH had no effect on grooming or rearing
      behavior. No body or head shakes were observed after LHRH administration. Scoring
      of individual grooming elements demonstrated differences in action of the three
      peptides. Although both CRH and TRH increased face grooming, only CRH induced
      head grooming. Furthermore, CRH induced predominantly head shakes while TRH
      increased body shake activity. In contrast, CRH was anxiogenic and TRH appeared
      to induce stereotyped behavior. From the characterization of grooming elements
      and related responses, we conclude that each hypophysiotropic peptide induces a
      specific behavioral pattern.

PMID- 8736134
TI  - Differential production of nitric oxide by endotoxin-stimulated rat and mouse
      neutrophils.
AB  - There is controversy regarding the evidence for the production of nitric oxide
      (NO) by neutrophils (PMNs). The present study investigates NO production, as
      assessed by the biosynthesis of the end products, nitrite and nitrate, in the
      pellets and supernatants of rat and mouse peripheral blood neutrophils obtained
      during endotoxemia and of peritoneal carrageenin-elicited PMNs stimulated in
      vitro with E. coli lipopolysaccharide (LPS). We also investigated the induction
      of NO synthase by rat and mouse peritoneal cells. The intraperitoneal (ip)
      administration of LPS to mice (10 mg/kg) and rats (5 mg/kg) significantly
      increased plasma nitrate concentration by six and 23-fold, respectively. In vivo
      pretreatment with L-NGmonomethyl arginine (L-NMMA) significantly inhibited this
      production. Compared to animals injected with PBS, the cell pellets of blood PMNs
      obtained from mice, but not rats, 2 or 6 h after LPS administration produced
      significant amounts of nitrite (14 +/- 3 and 18 +/- 2 nmol/mg protein,
      respectively). Little or no nitrite was found in the incubating medium. In
      contrast, 6 h after a carrageenin challenge (700 micrograms) peritoneal
      neutrophils obtained from rats, but not mice, released high concentrations of
      nitrite into the supernatant during a 24-h period of incubation (34 +/- 0.8
      microM). The nitrite concentration of the pellet of these cells was negligible.
      In contrast to the lack of increase in the amount of nitrite released into the
      supernatants, the in vitro stimulation of rat PMNs with LPS (10 micrograms/ml)
      for 24 h did increase intracellular nitrite concentration (from 0.8 +/- 0.07 to 8
      +/- 0.3 nmol/mg protein). In mouse PMNs, LPS treatment caused only a small
      release of nitrite into the incubation medium (14 +/- 1 microM). There was no
      significant change in nitrite concentration in the cell pellets. These data
      suggest that rat and mouse neutrophils differ in their ability to produce nitric
      oxide following stimulation with endotoxin.

PMID- 8736135
TI  - 2-Pyridylarylhydrazone derivatives, a new class of platelet aggregation
      inhibitors.
AB  - A series of 2-pyridylarylhydrazone derivatives was synthesized and compared with
      a previously reported pyrazole series, i.e., 4-acylpyrazolylarylhydrazone and 5
      pyrazolylarylhydrazone, which present antiplatelet aggregation activity. The
      structures of these pyridylarylhydrazone derivatives were designed on the basis
      of the known bioisosteric relationship of the heteroaromatic ring. The
      antiplatelet aggregation activity was measured in vitro on citrated platelet-rich
      rabbit plasma in which aggregation was induced with 5 microM ADP, 5 micrograms/ml
      collagen and 200 microM arachidonic acid. Eighteen compounds belonging to the
      pyridine series were tested at 1 mM concentration and none inhibited ADP-induced
      rabbit platelet aggregation. 2-(2-Formylfurane)pyridylhydrazone exhibited a
      highly potent inhibitory activity on arachidonic acid-induced aggregation, with
      an IC50 of 0.35 microM. These results suggest that the hydrazone unit and the 2
      furyl moiety of the arylhydrazone framework are important pharmacophores for
      antiplatelet activity.

PMID- 8736136
TI  - Sexual development of hypernatriophilic male rats up to puberty.
AB  - The sexual development of normonatriophilic (Normo) and hypernatriophilic (Hyper)
      male Wistar rats was compared from 30 to 60 days of age (N = 8-10 per group) with
      emphasis on the onset of puberty. Hyper rats (more than 5 ml of saline a day in a
      situation of free access to tap water and 1.5% NaCl) had a 20-39% body weight
      reduction and a 22-29% testicular growth rate decrease compared to Normo rats.
      Plasma testosterone (ng/ml) of Normo rats increased from 0.29 +/- 0.02 at 30 days
      to 1.42 +/- 0.18 at 50 days, decreasing to 0.87 +/- 0.15 at 60 days of age, with
      no significant difference compared to Hyper animals. Plasma concentration (ng/ml)
      of luteinizing hormone (LH) was significantly lower in Hyper (0.21 +/- 0.03) than
      in Normo (0.43 +/- 0.06) rats at 40 days. At 30 days, plasma follicle stimulating
      hormone (FSH) levels (ng/ml) were significantly higher in Hyper (18.9 +/- 1.3)
      than in Normo (15.6 +/- 0.5) rats. It is possible that increased levels of FSH
      compensated for a reduced amount of LH, thus allowing similar testosterone
      production by Hyper and Normo rats. At 30 days, testis maturation was higher in
      Hyper rats, as indicated by a 22% increase in tubular cross-sections with young
      spermatids. At 50 days, spermatogenesis progressed to the production of mature
      spermatids (onset of puberty) and Hyper rats exhibited an 18.7% lower rate of
      testis maturation. Testis maturation was similar in Hyper and Normo rats at 60
      days.

PMID- 8736137
TI  - [Neuromuscular action of crotalid venoms: preliminary data].
AB  - We studied 6 patients and 2 dogs that have been bitten by South American
      rattlesnake Crotalus durissus terrificus and one rabbit inoculated with crotalid
      venom. We analyzed sensory and motor peripheral nerve conduction, repetitive
      stimulation for studying neuromuscular transmission and electromyographies.
      Muscle biopsies were processed by histochemistry. All patients had peripheral
      mononeuropathy of the closest sensitive nerve to the area of snakebite. The
      neuromuscular transmission alterations were minimal. Muscle histochemistry of 4
      patients, 2 dogs and 1 rabbit showed findings of mitochondrial myopathy. The
      majority of authors admit that crotalid venom causes myastenic syndrome. Our
      findings suggest that palpebral ptosis, myastenic facies and muscular weakness
      observed after crotalid poisoning are, probably, due to transient and reversible
      mitochondrial myopathy. As far as we know, this is the first report on the
      ability of the venom of this rattlesnake to cause local sensitive mononeuropathy
      and the first muscle histochemistry showing mitochondrial myopathy in humans
      poisoned by crotalid venom.

PMID- 8736138
TI  - Electroneuromyography and neuromuscular findings in 16 primary hypothyroidism
      patients.
AB  - There has been few reports on electroneuromyography (ENMG) changes in
      hypothyroidism. The objectives of the present study were to investigate the
      frequency of ENMG abnormalities in hypothyroidism and correlate them with
      neurological signs and symptoms and muscle enzyme levels; and to compare latency,
      amplitude and nerve conduction velocity from selected nerves with controls.
      Sixteen patients suffering from primary hypothyroidism were submitted to ENMG
      before treatment. ENMG abnormalities were found in 87.5% of the patients; 46.6%
      had myopathy and 43.7% had carpal tunnel syndrome. There was no case of
      polyneuropathy. A clear-cut clinical, laboratorial and ENMG correlation was
      observed in patients with myopathy and carpal tunnel syndrome. The patients
      showed a significant tendency of nerve conduction slowness as compared with
      controls. The findings are in accordance with the well-known nerve and muscle
      damage in hypothyroidism.

PMID- 8736139
TI  - [Sural nerve biopsy in myotonic muscular dystrophy].
AB  - Twelve patients with myotonic dystrophy were studied to look for the involvement
      of the peripheral nervous system in this disease. All of them showed the main
      signs and symptoms of the disease. They did not have another causes to justify a
      polineuropathy. They were submitted to sural nerve biopsy with counting of
      myelinated fibers and histogram. Patients showed a reduction in the number of
      myelinated fibers and in two patients the histogram was unimodal. We concluded
      that polineuropathy may be another multisystemic manifestation of myotonic
      dystrophy.

PMID- 8736140
TI  - [Attention deficit disorder: treatment with methylphenidate].
AB  - The authors present the results of the treatment with methylphenidate in 24
      children with attention deficit disorder based on DSM-III. The prescribed dose
      was 5 to 10 mg per day, once or twice a day. The results were good in 79.1% of
      the patients and poor in 16.6%. The drug was withdrawn in one patient because of
      side effects and the evaluation of efficacy was not possible. Side effects
      occurred in 2 children (headache and/or nausea). The therapeutic response and the
      side effects are compared with the literature. The authors claim attention to the
      efficacy and safety of the treatment with methylphenidate.

PMID- 8736141
TI  - [Dystonias: clinical and therapeutic aspects in 64 patients].
AB  - The experience with 64 patients with dystonia seen at the Extrapyramidal Diseases
      Sector of the Neurology Department of the Hospital Universitario Clementino Fraga
      Filho of the UFRJ is presented as well as the pertinent review of the literature.
      The five-and-a-half-year of follow-up showed that 33 were male and 31 female; 48
      were white, 10 mulatto and 6 negro; the mean time of disease was 9 years and 8
      months. According to the distribution of the movement disorder, 30 (46.9%) were
      focal, 17 (26.6%) segmental, 13 (20.3%) generalized, 3 (4.7%) hemidystonia and 1
      (1.5%) multifocal. In 11 (17.2%) the age of onset was before 12 years old, in 6
      (9.4%) between 13 and 20 years old, and in 47 (73.4%) after 20 years old.
      According to the etiology, 39 (60.9%) were idiopathic sporadic, 6 (9.4%) were
      idiopathic familial and 19 (29.7%) were symptomatic. The therapeutical approach
      used in these patients were anticholinergic drugs, dopaminergic agonists or
      antagonists and baclofen, alone or associated with anticholinergic drugs for
      generalized dystonia. The authors conclude that botulinum toxin type A is the
      most valuable therapeutic agent in the treatment of focal dystonia.

PMID- 8736142
TI  - Rural or urban living and Parkinson's disease.
AB  - Although the precise etiology of Parkinson's disease (PD) is as yet unknown, it
      appears that certain environmental factors are involved. Prior living in a rural
      area has been implicated as a possible risk factor for PD, particularly in the
      early onset type. We evaluated the role of previous living conditions in the
      clinical correlates and outcome characteristics of 118 PD patients. All of them
      were seen from January 1987 to October 1992. The Rural Group (RG) comprised 71
      patients (60.2%) who had lived in the rural area for at least 10 years (mainly in
      early phase of life) and the Urban Group (UG) consisted of 47 patients (39.8%)
      who had lived their entire life in an urban environment. The average age at the
      beginning of the symptoms was 58.8 in the RG and 54.1 in the UG. The mixed form
      of the disease (tremor, rigidity and akinesia) was the most frequent in both
      groups. A minimum 6-month follow-up period was undertaken with 63 patients
      (average 20 months) and no difference in response to treatment or in progression
      of the illness was detected between the two groups. Our data show that the
      previous living environment does not appear to be a determining factor in either
      the clinical or outcome characteristics of PD.

PMID- 8736143
TI  - High doses of carbamazepine for refractory partial epilepsy.
AB  - Forty-eight patients with partial seizures were analysed during treatment with
      1200 mg/d or more of carbamazepine (CBZ). Thirty-three were on monotherapy and
      fifteen on polytherapy. The other drugs were kept unchanged in the patients on
      polytherapy. The dose of CBZ was increased if no control was observed and the
      patient had no side effects. The doses used ranged between 1200 and 1900 mg/day
      (1200 mg/day, n = 18; 1300 mg/day, n = 1; 1400 mg/day, n = 7; 1600 mg/day, n = 9;
      1700 mg/day, n = 4; 1800 mg/day, n = 8; 1900 mg/day, n = 1). Anticonvulsant
      plasma levels were taken to confirm patient compliance. The average plasma level
      was 9.6 ug/mL. The period of follow up varied from 3 to 96 months (M = 25.6).
      Seizure's control was observed in 7 (14.48%) patients taking 1200 mg/day and in 2
      (4.16%) patients taking 1400 mg/day of CBZ. Thirty-nine patients did not show any
      control (81.21%). Ten patients (20.81%) had signs of intoxication. When patients
      have no improvement with 1400 mg/day, it is difficult to obtain any control
      despite the use of higher doses of CBZ, which frequently expose the patient to
      significant side effects.

PMID- 8736144
TI  - Allergic skin rash with lamotrigine and concomitant valproate therapy: evidence
      for an increased risk.
AB  - Cutaneous rash is one of the commonest adverse events associated with
      lamotrigine. We assessed whether the risk is increased in patients receiving
      concomitant valproate therapy in a population of 103 adult patients with
      intractable epilepsy, who had lamotrigine added to their treatment. Of the 33
      patients taking valproate, 10 (30%) developed a rash, whilst of the 70 not taking
      valproate, only 6 (8%) developed a rash. This suggests a significantly higher
      risk of cutaneous rash when starting lamotrigine in patients already taking
      valproate (p < 0.02).

PMID- 8736145
TI  - [Digital EEG with brain mapping in Alzheimer's dementia and Parkinson's disease.
      A prospective controlled study].
AB  - In order to evaluate the EEG activity during wakefulness in senile dementia of
      the Alzheimer type (AD) and Parkinson's disease (PD), a prospective controlled
      study was performed. We compared 6 AD and 11 PD patients with a control group of
      12 patients with mild to moderate major chronic depression (DSM-III-R, 1987). The
      median of the frequencies and the power of the posterior dominant activity was
      obtained in the three groups using spectral analysis. The posterior activity had
      a frequency of 8.79 +/- 0.52 (mean +/- sd) in the control group, 6.65 +/- 0.80
      (mean +/- sd) in the AD group and 7.69 +/- 1.39 (mean +/- sd) in the PD group.
      The experimental hypothesis that patients with AD and PD differ from controls in
      relation to the background activity (defined as abnormal < 8) was confirmed by
      the chi square test (p = 0.01) and the t test showed that the mean of the
      frequency of the posterior power was significantly lower in AD (p = 0.01) and PD
      (p = 0.05) patients, compared with the controls. The results indicate that this
      abnormality could be correlated with the degree of cortical damage and natural
      history of these disorders.

PMID- 8736146
TI  - Risk factors for unpleasant paresthesiae induced by paresthesiae-producing deep
      brain stimulation.
AB  - Paresthesiae-producing deep brain stimulation (stimulation of ventrocaudal
      nucleus-VC, medial lemniscus-ML or internal capsule-IC) is one of the few
      procedures to treat the steady element of neural injury pain (NIP) currently
      available. Reviewing the first 60 patients with NIP submitted to deep brain
      stimulation (DBS) from 1978 to 1991 at the Division of Neurosurgery, Toronto
      Hospital, University of Toronto, we observed that 6 patients complained of
      unpleasant paresthesiae with paresthesiae-producing DBS, preventing permanent
      electrode implantation in all of them. Such patients accounted for 15% of the
      failures (6 out of 40 failures) in our series. In an attempt to improve patient
      selection, we reviewed our patients considering a number of parameters in order
      to determine risk factors for unpleasant paresthesiae elicited by paresthesiae
      producing DBS. The results showed that this response happened only in patients
      with brain central pain complaining of evoked pain, secondary to a supratentorial
      lesion. Age, sex, duration of pain, quality of the steady pain, size of the
      causative lesion and site (VC,ML,IC) and type (micro or macroelectrode) of
      surgical exploration were not important factors. Unpleasant parethesiae in
      response to dorsal column stimulation, restricted thalamic lesion on computed
      tomography and the occurrence of associated intermittent pain were considered
      major risk factors in this subset of patients and the presence of cold allodynia
      or hyperpathia in isolation and the absence of sensory loss were considered minor
      risk factors. It is our hope that the criteria here established will improve
      patient selection and so, the overall results of DBS.

PMID- 8736147
TI  - [Stereotactic surgery for intracranial mass lesions: diagnosis and treatment].
AB  - The authors present a study about 50 stereotactic procedures for intracranial
      lesions. In 12 cases stereotaxis was used as a treatment: stereotactic surgical
      resection (5 patients) and aspiration of lesions (7 patients). This study
      confirms the great accuracy and low morbidity of the stereotactic techniques.
      Computed tomography and magnetic resonance imaging determinate the precise
      stereotactic coordinates, but in some cases it is necessary to perform stereo
      angiography. The stereotactic surgical resection of brain tumors allows the
      treatment of deep lesions or located at functional areas and considered to be
      inoperable before. The related literature is discussed.

PMID- 8736148
TI  - [Chronic subdural hematoma: analysis of 35 cases].
AB  - Thirty five patients with chronic subdural hematoma were treated surgically
      between 1988 and 1995. The patients, aged 19 to 80 years, were graded
      retrospectively according to the Bender scale. The clots were removed via burr
      holes with irrigation of the subdural space to ensure as complete an evacuation
      of subdural collection, and craniotomy with membranectomy. The mortality rate was
      16.6% with craniotomy and 0% with burr-hole. The patients who died, 80% were in
      grade III or IV. The pathogenesis and surgical treatment of chronic subdural
      hematoma has been controversial, and still remains obscure.

PMID- 8736149
TI  - [Neonatal bacterial meningitis: prospective study of the long-term outcome of 55
      children].
AB  - Fifty-five infants who presented bacterial neonatal meningitis were prospectively
      studied to analyze the frequency and the type of sequelae. All the infants were
      full term newborns. There were 38 boys and 17 girls; the age of disease onset
      varied from 3 to 28 days. The causative organism was represented mainly by
      enterobacteriae. The median time of follow-up was 5 years. The frequency of
      neurologic sequelae was 63.7%, represented mainly by neuropsychomotor development
      delay (58.2%), hydrocephaly (45.5%) and convulsions (34.5%). Severe motor
      abnormalities ocurred in 23.6% of children (quadriplegia, diplegia, hemiparesia
      and ataxia). Convulsions in the acute phase of the disease and the positive
      cerebrospinal fluid culture were highly associated to sequelae. The school
      performance, obtained in 25 children, showed presence of disabilities in 48% of
      cases, which were significantly associated to mental retardation.

PMID- 8736150
TI  - Severe forms of neurocysticercosis: treatment with albendazole.
AB  - Study of 22 patients with the severe form of neurocysticercosis treated with
      albendazole (ABZ) administered in 6 different schedules ranging from 15 to 30
      mg/kg/day for 21 to 60 days. Dextrochloropheniramine and ketoprofen were the
      adjuvant drugs. Multiple symptoms were observed in 90.9% of patients.
      Intracranial hypertension was manifested in 90.9%. Hydrocephaly occurred in
      86.4%. Evolution was satisfactory in 10 patients, 8 died and 4 had sequelae.
      Tomographic studies showed the appearance of an isolated IVth ventricle in 9
      patients, after ventriculoperitoneal shunt, before ABZ treatment in 3 of them,
      during in 5 and after treatment in one. Median clinical follow-up duration was 10
      months for the patients who died and 3-4 years for survivors. In 3 patients there
      was an increase in cyst size during the administration of the 15 mg/kg/day ABZ
      dose, which was not observed in any patient when the 30 mg/kg/day dose was used.

PMID- 8736151
TI  - Cerebral cysticercosis in Campina Grande, Paraiba--northern Brazil. Computerized
      tomography diagnosis importance.
AB  - Neurocysticercosis is the infection of the central nervous system by the larval
      form of Taenia solium, the Cysticercus cellulosae. We studied 4011 computerized
      tomographies performed in TomoHPI Radioimaging Service, Hospital Pedro I, Campina
      Grande PB, Northern Brazil, since its installation on August 1993 to July 1995.
      41 patients were diagnosed as having Cysticercus cerebral infestation,
      corresponding to an incidence of 1.02%. No cases were related in Campina Grande
      PB during 1991 according to hospitalizations under prospective payment rates.
      After this radioimaging service installation, we observed 1.86 cases per month.
      We conclude that Campina Grande has to be included as an endemic area of
      neurocysticercosis, needing health service measures to cease the cycle Taenia
      Cysticercus, the only way to get rid of such a serious problem.

PMID- 8736152
TI  - Local IgG synthesis in three pediatric patients with Cuban epidemic neuropathy.
AB  - Three pediatric patients with Cuban epidemic neuropathy were studied.
      Cerebrospinal fluid and sera were simultaneously obtained. Albumin and IgG were
      quantified by immunodifusion. Albumin quotient and local synthesis of IgG were
      calculated by Reiber/Felgenhauer formula. A patient with optic neuritis had a
      dysfunction of the blood-cerebrospinal fluid barrier. All the group had local
      synthesis of IgG.

PMID- 8736153
TI  - Trypanosoma cruzi meningoencephalitis in AIDS mimicking cerebral metastases: case
      report.
AB  - A case of Chagas' meningoencephalitis in a 47 year-old patient with AIDS is
      presented. The diagnosis was established by examination of the cerebrospinal
      fluid which showed the presence of Trypanosoma cruzi. CT-scan revealed multiple
      cerebral lesions which only became evident by contrast administration. A second
      CT after 13 days showed a severe evolution with displacement of the midline
      structures leading to the patient's death. This case, as well as other case
      reports published, has shown the fulminant evolution of Chagas'
      meningoencephalitis in AIDS patients and the importance of cerebrospinal fluid
      examination for the diagnosis.

PMID- 8736154
TI  - [Polyradiculoneuritis and neurocysticercosis: report of a case].
AB  - Report of a patient with the hydrocephalic and meningoencephalitic form of
      neurocysticercosis who simultaneously developed polyradiculoneuropathy and
      intracranial hypertension syndrome during the first week of treatment with
      albendazole. Etiologic agents associated with polyradiculoneuropathy related in
      the literature are cited. Some comments about the possible physiopathogeny of
      this entity in the presence of cysticercosis are also done. It is mentioned
      another case who presented polyradiculoneuropathy as the only manifestation of a
      probable cysticercosis of the nervous system. In this presented case, including
      the neurocysticercosis and even a mere coincidence of facts, some factors can
      have a relationship with the appearance of polyradiculoneuropathy as the surgical
      stress, the stress due to the severity of the clinical picture and the possible
      side effect of albendazole.

PMID- 8736155
TI  - [Nemalinic myopathy with intracytoplasmic spheroid bodies: report of a case].
AB  - The authors report the case of a female patient, 18 years of age, with slowly
      progressing weakness in upper and lower limbs since childhood. There were no
      significant antecedents. The neurologic examination showed mild proximal and
      distal motor deficit with a slight muscular retraction at the level of shoulders,
      elbows, coxofemural joints, knees and ankles; muscular hypotrophy in the legs and
      feet; reflexes were present and sensitivity was normal. Creatinephosphokinase
      showed an increase of one and a half times the normal value.
      Electroneuromyography: decrease in the amplitude and duration of action
      potentials and excessive recruitment of motor units, compatible with a primary
      muscular disease. A muscle biopsy with frozen sections (HE, Gomori, PAS, ATPases,
      NADH, SDH, acid and alcaline phosphatases, cytochrome oxidase and Oil-red-o)
      revealed a primary muscular disease characterized by the presence of nemalinic
      and intracytoplasmic spheroid bodies. Nemalinic bodies have been described with
      different structural abnormalities of muscle fibers; however, such association is
      rare. This is the second case report of concomitant occurrence of nemalinic and
      spheroid bodies.

PMID- 8736156
TI  - [Pyle's syndrome: report of a case].
AB  - Pyle's syndrome is a rare picture of osseous dysplasia with autosomal recessive
      inheritance beginning in early childhood. The authors report the case of a 15
      years-old female patient with bilateral lower motor neuron facial palsy,
      progressive hearing loss, salience of frontal bone, metaphyseal enlargement of
      the lower limbs and genu valgus. In the present paper we briefly review the
      clinical features and the differential diagnosis of Pyle's syndrome.

PMID- 8736157
TI  - [Breast adenocarcinoma metastatic to the pituitary gland: report of a case].
AB  - A case of breast adenocarcinoma metastatic to the pituitary gland in a 57-year
      old Brazilian female is presented. The computerized imaging may cause
      differential diagnostic confusion between a benign primary pituitary process and
      metastatic disease. Resolution of doubts by surgery is important for determining
      appropriate treatment.

PMID- 8736158
TI  - Obsessions of infanticide and imminent psychosis.
AB  - In young mothers an obsession of infanticide, that is, fear that they may murder
      their children, may be coupled with an obsession of imminent psychosis, that is,
      fear that the first obsession is a sign of approaching insanity. Sixteen mothers
      with this clinical picture were evaluated in interviews. Seven of them entered
      psychotherapy and improved. The causative factors in childhood and adolescence
      wich led to the later development of these obsessive difficulties are analyzed.
      Even when psychotherapy was not possible, as was the case in nine patients, they
      should be strongly reassured and explanations should be given about the nature of
      the problem, for such encouragement and clarification helps them to improve to a
      significant extent. The prognosis of patients who have systematic psychoterapy is
      good.

PMID- 8736159
TI  - [Tropical spastic paraparesis: a necessary redefinition].
AB  - The author disserts on the definition of Tropical Spastic Paraparesis since its
      first description up to the etiological involvement of HTLV-1 in part of the
      cases. According to him the basic nucleus of the syndrome consists of a
      paraparesis with pyramidal signs (spasticity and hyperreflexia) with variable
      sensory and sphincter symptoms. The retroviral etiology by HTLV-1 is one of the
      variable elements of the condition. He aims at preventing conceptual distortions
      in the description of this condition.

PMID- 8736160
TI  - [Dystonia: concepts, classification, and physiopathology].
AB  - Since the last decades of the past century there have been several reports in the
      medical literature describing patients with dystonia. The clinical and
      phenomenological concepts of dystonic movements have been debated. Presently,
      dystonia is defined as a syndrome of sustained muscle contractions, frequently
      causing twisting and repetitive movements, or abnormal postures. Dystonia is
      usually classified according to three criteria: distribution, age of onset and
      etiology. The generalized forms often have their onset at childhood whereas the
      focal forms are most commonly seen in adults. Dystonic movements and postures can
      occur during resting or they can be precipitated by voluntary movements or by the
      adoption of specific posture patterns. The pathophysiologic mechanisms related to
      the appearance of dystonia are presently unknown. However, there are compelling
      evidences suggesting the involvement of some basal ganglia nuclei (e.g. putamen
      and globus palidus) in the development of dystonia.

PMID- 8736161
TI  - [Dystonia: therapeutic aspects].
AB  - Several approaches have been employed for the treatment of dystonias. Possible
      specific causes should be searched for and specific treatment should be
      instituted. Different types of symptomatic treatment are grouped according to the
      following categories: pharmacological systemic therapy, surgical therapy and
      botulinum toxin injections in the affected muscles. Each of these approaches has
      its advantages and limitations. Generalized dystonias should be treated with
      anticholinergic agents. In some cases, levodopa or other drugs such as dopamine
      antagonists, baclofen and benzodiazepines should be preferred. Focal dystonias
      respond dramatically to local injections of botulinum toxin. Over 90% of patients
      with blepharospasm and 70% of patients with cervical dystonia present a
      satisfactory response to this procedure. Surgical approaches have been utilized
      in some cases of generalized (stereotaxic lesions), axial (rhizotomies) and focal
      dystonias (myectomies and neurectomies) with variable results.

PMID- 8736162
TI  - [In memoriam: Horacio Martins Canela (1919-1995)].

PMID- 8736165
TI  - Correspondence.

PMID- 8736166
TI  - The role of photodynamic therapy in the management of oral cancer and precancer.

PMID- 8736167
TI  - Stage of disease confounds apparent relationship between levels of N-ras and
      duration of survival in head and neck tumours.
AB  - The objective of this study was to determine whether elevated levels of N-ras
      correlated with clinicopathological data. Complete clinical data were available
      on 133 of 481 patients surgically treated for squamous cell carcinoma of the head
      and neck (SCCHN) who had immunohistochemical data for N-ras. Advanced stages of
      disease were strongly related to the staining for N-ras in tumour cells (P =
      0.0031). The stage of disease was inversely related to duration of survival (P =
      0.0017). Initial statistical evaluation revealed an apparent correlation between
      survival and N-ras staining. However, duration was found to be independent of the
      level of N-ras. The illusory relationship initially was a result of the
      confounding effect of the stage of disease.

PMID- 8736168
TI  - Expression of bFGF, KGF and FGF receptors on normal oral mucosa and SCC.
AB  - Fibroblast growth factors (FGFs) are involved in the transmission of signals
      between the epithelia and connective tissue, and influence epidermal growth and
      differentiation. They are thought to be important in the restoration of normal
      tissues after injury and aberrant expression may also play a role in
      tumorigenesis. However, no information is available on the nature of cells within
      oral mucosa which synthesise and/or respond to FGFs. We have screened normal oral
      mucosa and oral squamous cell carcinoma (SCC) for expression of bFGF by
      immunohistology and northern analysis and used RT-PCR to look for transcripts for
      KGF and the high-affinity FGF receptors FGFR1 and FGFR2. Transcripts for bFGF
      were detected in normal and malignant oral mucosa and KGF within connective
      tissue elements. The predominant FGF receptor detected in the epidermis and oral
      mucosa was FGFR2 which binds KGF with greater affinity than bFGF. Production of
      KGF by connective tissue components and synthesis of the high-affinity KGF
      receptor, FGFR2, by oral keratinocytes provides circumstantial evidence for a
      paracrine growth control loop with KGF synthesised within the lamina propria or
      tumour stroma influencing the proliferation and maturation of both normal oral
      epithelium and SCC.

PMID- 8736169
TI  - Prognostic factors of survival in a cohort of head and neck cancer patients in
      Oslo.
AB  - A cohort of 433 Oslo patients with head and neck (H/N) carcinomas was analysed
      for prognostic factors of survival. Mean observation time was 635 days, the
      distribution of men and women was 2:1 and the mean age was 64.5 years. Tumour
      localisations were: oral cavity 32.1%, oro/hypopharynx 19.3%, larynx 22.6% and
      others 25.2%. Stage distribution was: stage I: 21.0%, stage II: 22.6%, stage III:
      18.7% and stage IV: 37.4%. Pragmatic strategy showed independent prognostic
      factors of survival to be gender, age, tumour localisation and stage. A model of
      predicting 3 year survival was generated. An explanatory approach showed that
      female patients had a 38% lower risk of mortality compared to male patients after
      controlling for age, stage and tumour localisation. Comparing observed to
      expected mortality of the age and gender matched Norwegian population, showed
      excess risk of death among male compared to female patients when also adjusted
      for demographic confounders.

PMID- 8736170
TI  - Nuclear morphometry in squamous cell carcinoma (SCC) of the tongue.
AB  - In the histological grading of oral squamous cell carcinoma (OSCC) nuclear
      features are very important. Nevertheless evaluation is usually performed in a
      subjective and not highly reproducible way. The aim of this work was to
      investigate the relationship between nuclear shape and survival in 30 cases of
      carcinoma of the tongue. All the patients were divided into two groups: short
      term survival and long-term survival. Twenty nuclei for each tumour were
      submitted to a morphometrical study by the shape analytical morphometry (SAM)
      software system. It was thus possible to evaluate not only nuclear dimensions but
      also nuclear contour irregularities and nuclear shape asymmetries. Multivariate
      discriminant analysis (MDA) of the quantitative parameters obtained by the
      morphometrical study distinguished the patients of the two groups with only a 10%
      error; moreover successful cluster analysis was performed by using Fourier
      parameters. Both these sets of results were achieved mainly owing to the
      parameters for contour irregularities.

PMID- 8736171
TI  - Growth pattern of experimental squamous cell carcinoma in rat submandibular
      glands--an immunohistochemical evaluation.
AB  - Histopathological and immunohistochemical studies during carcinogenesis in rat
      submandibular glands (SMGs) using a carcinogen (9,10-dimethyl-1,2-benzanthracene:
      DMBA) were evaluated. For carcinogenesis, the carcinogen-containing sponge was
      surgically inserted into the gland. Histopathological features during
      carcinogenesis were as follows; dilatation of ductal segments, the presence of
      duct-like structures and cystic lesion around the sponge were observed within 3
      weeks of the experiment, squamous metaplasia in duct-like structures and lining
      epithelium of the cystic structures around the sponge were observed at 4-6 weeks
      of the experiment, and finally well differentiated squamous cell carcinomas
      (SCCs) were observed after 8 weeks of the experiment. The immunoreactivity of
      K8.12 keration (K8.12), S-100 protein (S-100), epidermal growth factor (EGF),
      laminin, and proliferating cell nuclear antigen (PCNA) were evaluated. In the
      normal SMG, EGF was confined to the granular cells and S-100 to the pillar cells
      of granular convoluted tubules (GCTs). K8.12 was found in striated (SD) and
      excretory duct (ED) cells and laminin showed linear staining of the basement
      membrane around the ducts, acini and blood vessels. PCNA-positive nuclei were
      rarely observed in the normal glandular parenchyma. During carcinogenesis, during
      the first stage, EGF in granular cells and S-100 in pillar cells of GCT segments
      disappeared, and cytokeration K8.12 was observed in duct-like structures and
      cystic epithelium around the DMBA sponge. PCNA-positive nuclei in the first stage
      were mainly confined to basal cells of morphologically altered ducts. During the
      second stage, squamous metaplastic cells showed an intense K8.12 reaction. During
      the third stage, the well differentiated SCC showed strong reaction for K8.12,
      and the linear staining for laminin staining had disappeared at the invading
      fronts. The PCNA index was nearly 40% in the tumour cell component. The stem
      cells or the progenitor cells during experimental carcinoma were most likely to
      be the ductal basal cells, and carcinogenesis was initiated with an increase of
      proliferating activity in small cell clusters surrounding a necrotic area, basal
      cells of dilated excretory ducts and duct-like structures. Thus, all ductal
      segments undergoing squamous metaplasia may participate in the genesis of
      neoplasia during experimental carcinogenesis.

PMID- 8736172
TI  - Tenascin: growth and adhesion modulation--extracellular matrix degrading
      function: an in vitro study.
AB  - Tenascin (TN), a recently characterised extracellular matrix protein, largely
      confined to the process with the development of embryo in areas of epithelial
      mesenchymal interactions and in areas where there are morphogenetic movements and
      tissue patterning, has a highly restricted expression in adult tissues. The
      expression of TN is enhanced in a variety of human neoplastic lesions. However,
      function(s) and molecular mechanisms of enhanced expression in neoplastic lesions
      remain unclear. We employed human tongue carcinoma cells (SCCKN), human salivary
      gland adenocarcinoma cells (SGT-1), normal mouse embryonic fibroblasts (NIH3T3-3)
      and K-ras-2 transformed fibroblasts (Cle-H3) in an in vitro study to elucidate
      the biological roles of TN. In in vitro studies, all the cell lines examined had
      enhanced secretion of TN in the presence of transforming growth factor-beta in a
      dose-dependent manner and TN itself was found to possess a growth-enhancing
      activity. Moreover, studies on adhesion of the cell lines on coated substrates of
      fibronectin (FN), laminin (LN), tenascin (TN), TN/FN and TN/LN showed that all
      the cells adhere and spread well on FN and LN. However, on TN they attach poorly
      and remain rounded. The relative concentrations of TN and FN affected the
      cellular adhesion and morphology. In SCCKN and SGT-1, but not in NIH3T3 and Cle
      He3 fibroblasts, a higher concentration of TN inhibited cellular adhesion on
      fibronectin, suggesting that cells attach poorly on TN, it may interfere with the
      action of fibronectin, and the relative concentrations of TN, FN or LN may affect
      cellular adhesion and morphology which may differ in different cell types. When
      TN was added in the growth medium of exponentially growing cells, the cells lost
      their cell to cell contact and were seen to be separating. The presence of these
      extracellular matrix proteins were further tested to determine whether they could
      modulate the secretion of proteolytic enzymes responsible for extracellular
      matrix degradation by tumour cells, when the neoplastic cells but not the non
      neoplastic cells grown on FN/TN substrate showed positive immunofluorescence for
      collagenase. FN, LN or TN alone did not induce collagenase in the tumour cells.
      If the same is true in vivo, although a number of factors and interactions may
      implicate the ultimate outcome, the enhanced expression of TN in neoplastic
      lesions may have potential implications for tumour growth, differentiation,
      cellular adhesion, invasion and metastasis.

PMID- 8736173
TI  - Vitamin E inhibits experimental carcinogenesis and tumour angiogenesis.
AB  - In an experiment in which vitamin E inhibited carcinogenesis, it was found that
      tumour angiogenesis and tumour growth-factor alpha (TGF alpha) expression were
      also inhibited. Forty male golden hamsters were divided into four equal groups.
      Group 1 animals had the left buccal pouches painted three times weekly with 7,12
      dimethylbenz(a)anthracene (DMBA) for 14 weeks. Group 2 animals had the same
      procedure of DMBA applications but also received alpha tocopherol. Groups 3 and 4
      were vitamin E and untreated controls. Angiogenesis was studied with factor 8
      related antigen (F8-RA) which identifies endothelial cells. TGF alpha was studied
      with the appropriate antibody. Staining was effected by the standard avidin
      biotin horseradish peroxidase system. Mean tumour volume was significantly lower
      in the DMBA-vitamin E group compared to the tumour control group. Angiogenesis
      was significantly inhibited in the DMBA-vitamin E group and TGF alpha expression
      was also inhibited. It is suggested that inhibition of tumour angiogenesis by
      vitamin E may be an additional mechanism for the anticancer action of vitamin E.

PMID- 8736174
TI  - Serum vitamins' status in oral leucoplakias--a preliminary study.
AB  - Vitamins, such as A, beta carotene, C, E, B12 and folate, are the micronutrients
      with the strongest evidence of having a link to cancer prevention and control.
      Deficiency of these vitamins at the dietary, systemic or mucosal level will
      interact with tobacco use and increase the risk of oral precancerous lesions. The
      objective of this study was to (1) establish the baseline circulating levels of
      these vitamins in our normal population with and without tobacco use and (2)
      compare these levels with the values obtained in cases of oral leucoplakias. 50
      normal controls with 25 each in chewers and non-chewers, matched for age and sex,
      were selected. 50 cases of oral leucoplakias (clinically detectable white
      patches) from the field constituted the study group. Simultaneous measurement of
      serum vitamin B12 and folate were carried out by radioassay. The other serum
      vitamins were estimated spectrophotometrically. Except for serum vitamin E, all
      the other serum vitamin levels were significantly decreased in oral leucoplakias
      compared to the controls. Cancer chemopreventive agents acting as inhibitors of
      both initiation and promotion, as analysed in our population, is promising for
      further intervention trials.

PMID- 8736175
TI  - Prognostic implications of Sialosyl-Tn antigen expression in sinonasal intestinal
      type adenocarcinoma.
AB  - The expression of the mucin antigen sialosyl-Tn (S-Tn) was evaluated
      immunohistochemically in a series of 30 intestinal type adenocarcinomas of the
      nasal cavities and paranasal sinuses to assess the relationship between the
      histological features of the lesions and their clinical behaviour. In grades 1
      and 2 adenocarcinomas, the staining localised at the apical pole or within the
      cytoplasm of neoplastic cells, and in the content of glandular structures. Grade
      3 adenocarcinomas had a very scanty expression of the antigen. Mucinous
      adenocarcinomas showed an intense immunoreaction within the cell cytoplasm and in
      the extracellular mucous pools. Conversely, non-neoplastic sinonasal mucosa had a
      very focal distribution of the antigen. Immunostaining was scored according to
      the percentage of low power microscopic fields showing positivity. Twenty-one
      adenocarcinomas (70%) were considered positive. No significant relationship was
      found between S-Tn positivity and the histological degree of differentiation of
      the lesion. The 5-year survival rate and disease-free interval of patients with S
      Tn positive adenocarcinomas were significantly lower than those with negative
      adenocarcinomas (17.8% versus 72%, P = 0.0001; 16.6% versus 40%, P = 0.0001,
      respectively). These results indicate that S-Tn immunostaining appears to be a
      significant prognostic factor in patients with sinonasal intestinal type
      adenocarcinoma.

PMID- 8736176
TI  - Malignant salivary gland neoplasms: a cytogenetic study of 19 cases.
AB  - A group of 19 malignant salivary gland neoplasms of various histological types
      (mucoepidermoid carcinoma, acinic cell carcinoma, adenoid cystic carcinoma,
      epithelial-myoepithelial carcinoma, myoepithelial carcinoma, basal cell
      adenocarcinoma, carcinoma ex-pleomorphic adenoma, ductal carcinoma,
      adenocarcinoma not otherwise specified and undifferentiated carcinoma) were
      cytogenetically investigated. Previous karyotypic information revealed deletion
      of the long arm of chromosome 6, loss of chromosome Y and the gain of chromosome
      8 as the most recurrent deviations found in these neoplasms. Clonal chromosome
      aberrations were detected in 11 cases of this series. In 7 of them there were
      only numerical deviations (gain of chromosomes 2, 7, 8, 10 and X and loss of
      chromosomes 18, 21 and Y) without concomitant structural anomalies. Structural
      rearrangements such as t(2;7), t(6;16), t(6;9) and t(1;1) translocations were
      found in two mucoepidermoid carcinomas, one adenoid cystic carcinoma and one
      ductal carcinoma, respectively. The wide spectrum of changes found in this group
      of neoplasms may reflect the diversity in their histogenesis and differentiation
      phenotypes.

PMID- 8736177
TI  - Sweet's syndrome in a patient with oral cancer associated with radiotherapy.
AB  - Approximately 10-20% of the reported patients with acute febrile neutrophilic
      dermatosis (Sweet's syndrome) have an associated neoplasm. Oral findings of
      Sweet's syndrome are rarely reported, and no cases in patients with oral cancer
      have been reported to date. This report describes the clinico- and
      histopathological findings of Sweet's syndrome in a patient with oral cancer,
      treated with radiotherapy. After 10 fractions of external beam radiotherapy,
      treatment was interrupted because of severe oral mucositis which extended beyond
      the radiation fields. Two days later the patient developed multiple tender skin
      lesions and the diagnosis Sweet's syndrome was made. Skin and oral lesions
      resolved without additional treatment and did not recur upon resuming
      radiotherapy. As suggested in previous case reports, tumour antigens might play a
      role in the development of Sweet's syndrome. In this case, irradiation therapy
      may also have been a trigger for this syndrome.

PMID- 8736178
TI  - Oral verruca vulgaris in a bone marrow transplant patient: a case report and
      review of literature.
AB  - Viral infections can cause severe morbidity in immunosuppressed cancer patients.
      A case of rapidly enlarging, biopsy-documented oral verruca vulgaris in a patient
      undergoing conditioning chemotherapy prior to bone marrow transplantation (BMT)
      is described. Human papillomavirus infections in immunosuppressed patients are
      discussed.

PMID- 8736179
TI  - Integration of medical education and the health care system.

PMID- 8736180
TI  - 'Cultural imperialism': a danger?

PMID- 8736181
TI  - Integrating medical education and health services: the Iranian experience.

PMID- 8736182
TI  - The essential role of the student in curriculum planning.
AB  - Medical school curricula are planned, written and organized by academic and
      clinical staff within medical schools. While these medical educators may well be
      experts in their given field, they lack first-hand experience of what it is to be
      a medical student in 1995. For a medical curriculum to be an effective means of
      learning for today's students, it must be written with a knowledge of their
      priorities, needs and abilities. The way in which this can be best achieved is by
      the inclusion of current students in all stages of designing a new curriculum. In
      my second year of medicine at Flinders University, I became involved in planning
      for the new Graduate Entry curriculum. In the role of student advocate, I have
      found I am able to offer teaching staff a unique perspective, the student
      perspective, on various issues. Students, through experience from their own
      education, are able to give advice on student resources and facilities and are in
      a favourable position to judge other aspects of curricula, such as the balance
      and relevance of course content and assessment. Students need to realize the
      valuable insight they have to offer their faculties and the way in which this can
      benefit future students. It is by actively seeking student involvement and using
      their input, that faculties will be able to create a consumer-friendly
      curriculum.

PMID- 8736183
TI  - Attitudes of patients to medical student participation: general practice
      consultations on the Cambridge Community-Based Clinical Course.
AB  - The clinical medical students on the Cambridge Community-Based Clinical Course
      (CCBCC) derive part of their training by taking part in consultations between
      patients and their general practitioners. Patients' attitudes to this arrangement
      and their support for student training in a general practice setting are an
      important factor in the development of community-based education. A postal
      questionnaire seeking information from patients achieved an 84% response rate.
      Both the numerical results and the patients' comments are presented. Patients
      proved generally supportive of the community-based course and some identified
      positive benefits to themselves from this provision. The large majority of
      patients did not mind the presence of medical students during consultations,
      although there are some areas in which patients are less willing to involve
      students.

PMID- 8736184
TI  - The surgical clerkship: characteristics of the effective teacher.
AB  - A good relationship between medical students and clinicians is crucial to a
      positive learning experience. To increase contact between surgical teaching staff
      and students, a teacher programme was instituted in the problem-based surgical
      clerkship at the University of Kentucky. This study examined the teacher traits
      and skills that medical students perceive as distinguishing effective from
      ineffective teachers. The 312 evaluations collected from students in successive
      surgical clerkship rotations (87% response rate) were used to determine the
      characteristics of the effective teacher. Results suggest that students rate
      increased contact with surgical teaching staff highly and that they value
      increased mentoring by the staff. The traits of teachers rated highly by students
      in the surgical clerkship include: being a positive role model, encouraging
      communication, and being well organized. Comparing data from the 2 years of the
      clerkship also revealed that providing feedback to staff on their performance as
      teachers enabled them to improve their instructional skills.

PMID- 8736185
TI  - Crafting cases for problem-based learning: experience in a neuroscience course.
AB  - Clinical cases for problem-based learning should capture the relevance of patient
      encounters, and not serve merely as a 'take-off' point for scientific study. As a
      vehicle of learning, the case should drive the science and the science should
      drive the case. Decision points elicit intellectual commitment, and help to raise
      the level of inquiry. Our cases are focused, avoiding clinical complexity and
      reliance on pattern recognition. We emphasize formulation of evidence-based
      mechanistic hypotheses. The case does not stand alone, but must suit its position
      in the course and curriculum.

PMID- 8736186
TI  - Where should special attention be paid in undergraduate medical education? Two
      surveys among Finnish physicians.
AB  - The study focuses on Finnish doctors' views of their undergraduate medical
      education. In 1988, a study (Junior Physician 88 Study) involving all the doctors
      registered during the years 1977-1986 in Finland (n = 5208) was carried out. A
      questionnaire was sent to a random sample of 2632 doctors, and after two mailings
      1745 questionnaires (66.3%) were returned. A total of 1334 gave at least one
      answer to the question: 'Where should special attention be paid in undergraduate
      medical education?' Five years later, in 1993, another study (Physician 93 Study)
      involving all medical doctors registered in Finland during the years 1982-1991 (n
      = 4671) was carried out. The same questionnaire was sent to a random sample of
      2332 doctors, and after two reminders 1818 questionnaires (78.0%) were returned,
      and 1228 doctors also answered the open-ended question. Content analysis was used
      to analyse the answers qualitatively and quantitatively. About 90% of the answers
      could be classified into two main categories: practical skills and evaluation of
      subjects. The most common proposal for the improvement of undergraduate medical
      education was that the practical skills needed in general practice should be
      taught. More education in administration and health economics was also desired.
      Respondents said that preclinical and clinical studies should be more closely
      integrated. In answers to the open question, the course in public health was
      strongly criticized for being too theoretical. Learning of the core knowledge for
      medical practice was considered essential.

PMID- 8736187
TI  - Evaluating communication skills in the OSCE format: reliability and
      generalizability.
AB  - In most objective structured clinical examinations (OSCEs), communication skills
      are assessed as an 'add-on' to history-taking stations, rather than in stations
      designed to assess communication skills in the broadest sense. This study
      investigated the feasibility of developing such stations. In part one, 60
      clinical clerks and 36 residents were rated in four 10-min emotionally charged
      situations portrayed by standardized patients. Inter-rater reliability was
      demonstrated (r = 0.59-0.63) and a highly significant effect of educational level
      was found. Generalizability between communication stations was low (0.17-0.20).
      Several explanations for poor generalizability, including poor discrimination as
      a result of low score variance and the confounding effect of content knowledge,
      were addressed in part 2. Ninety-five final-year medical students participated in
      an OSCE in which six 10-min encounters examined the students' ability to manage
      difficult emotional situations such as fear, anxiety, mania, sadness, confusion
      and anger. Half the students encountered a patient with moderate emotional
      symptoms and half an extreme emotional state. For difficult stations, students'
      scores were lower and standard deviation higher, suggesting that manipulating
      difficulty increases score variance and potentially discrimination. However, a
      strong interaction was found between difficulty and station content, and
      communication scores were highly correlated with content. Scenarios which created
      major communication difficulties (such as mania) resulted in much larger
      differences in scores between the easy and difficult versions. Communication OSCE
      stations can be created with acceptable reliability including difficult cases
      which address communication skills beyond simple history taking. Nevertheless, a
      generalizable set of communication skills remains elusive.

PMID- 8736188
TI  - A closer look at cueing effects in multiple-choice questions.
AB  - This study investigates the cueing effect occurring in multiple choice questions.
      Two parallel tests with matching contents were administered. By means of a
      computer program, examinees of different training levels and professional
      expertise were presented the same set of 35 cases (derived from patient problems
      in general practice) twice. The first time the cases were linked to open-ended
      questions; the second time they were linked to multiple choice questions. The
      examinees consisted of 75 medical students from three different years of
      training, 25 residents in training for general practice and 25 experienced
      general practitioners. Across groups, total test scores reflected a difference in
      mean scores on both formats, and a high inter-test correlation. Within each level
      of expertise, differences in mean scores and high correlations were also found.
      The data were further explored per group of examinees. Two types of cueing
      effects were found: positive cueing (examinees were cued towards the correct
      answer) and negative cueing (examinees were cued towards an incorrect answer).
      These effects were found at all levels of expertise and in almost all items.
      However, both effects decline with increasing level of expertise. Positive cueing
      mainly occurs in difficult items, whereas negative cueing mainly occurs in easy
      items.

PMID- 8736189
TI  - Computerized long-menu questions as an alternative to open-ended questions in
      computerized assessment.
AB  - To optimally avoid cueing effects and computer scoring problems in computerized
      examinations a computerized long-menu question (CLM) was developed. This question
      type was compared to open-ended questions in one treatment group and to multiple
      choice questions in another treatment group. Also, scores were compared to self
      perceived computer anxiety of the participants. CLMs yield comparable scores to
      open-ended questions, but the scores differ significantly from those on multiple
      choice tests. Correlations in the first comparison (CLMs with multiple-choice)
      were higher than those in the second camparison (CLMs with open-ended questions).
      The amount of positive and negative cueing was considerably higher in the first
      than in the second comparison. Response times of CLMs were higher than those of
      multiple-choice questions and open-ended questions, differing significantly from
      both. Computer anxiety did not influence the mean scores in either comparison.
      Therefore, in computerized testing CLMs seem to offer an acceptable replacement
      of open-ended questions.

PMID- 8736190
TI  - Content specificity and oral certification exams.
AB  - This study reports on the generalizability of different skills assessed in the
      oral certification examinations in Internal Medicine of the Royal College of
      Physicians and Surgeons of Canada. Assessments from the 1992 examination were
      examined prospectively to determine (i) inter-rater reliability, (ii) correlation
      from morning to afternoon sessions, and (iii) overall test reliability. While
      inter-rater reliability was acceptable and in the range reported from previous
      studies, the generalizability across sessions was very low, ranging from 0.30 to
      0.47, presumably reflecting content specificity. As a consequence, the overall
      test reliability was low, ranging from 0.57 to 0.69. Collapsing the overall
      scores into three decision categories (pass, borderline, fail) lowered the test
      reliability still further. Strategies to resolve this problem are suggested.

PMID- 8736191
TI  - The effects of the introduction of a system of mandatory formative assessment for
      general practice trainees.
AB  - A series of questionnaires was used to determine the amount of formative
      assessment going on within the est of Scotland Region of the UK and its perceived
      value by trainees (General Practice [GP] Registrars) both at the beginning and
      end of training. The first survey was carried out in 1989 and the second in 1994.
      Trainers and course organizers were surveyed in 1994 to determine their attitudes
      to the use of videotaped consultations for formative assessment. In 1991, the
      region had initiated a mandatory formative assessment programme which included
      regular use of videotaped consultations, confidence rating scales and Manchester
      ratings (RCGP Occasional Paper Number 40). The use of a range of assessment
      methods for formative assessment of GP Registrars increased considerably between
      1989 and 1994. The percentage of trainees using videotaped consultation analysis
      increased from 76 to 94%, for Manchester ratings from 52 to 68% and for
      confidence rating scales from 63 to 74%. Video and confidence scales were rated
      highly by trainees who were assessed by them and by most trainees at the start of
      the year, but less highly by those who had not been assessed by them by the end
      of the trainee year. Manchester ratings were not thought to be as useful, and for
      these there was no difference between users and non-users. Despite the mandatory
      system, a significant number of trainees (76%) were still not receiving the
      minimum assessment stipulated. Trainers rated lack of time as the main limiting
      factor to the greater use of video. We conclude that trainees who are exposed to
      assessment methods, particularly video, find it useful, but that some trainees
      are still receiving less than is optimal. We propose increased trainer education
      and intensified monitoring of the assessment carried out in training Practices.

PMID- 8736192
TI  - A questionnaire examining learning in general practice.
AB  - Vocational training is a key element of professional development in general
      practice. Learner-centred approaches to teaching bring a need for greater
      understanding of the individual learning styles and preferences of trainees. This
      paper reports the findings of a pilot study undertaken to determine factors that
      may influence learning among general practice trainees. A questionnaire survey of
      261 trainees in six regions in the UK was carried out to explore attitudes to a
      series of themes identified in semi-structured interviews with trainees at the
      end of their training. Six distinct subscales were identified using principal
      components analysis. These are named 'Learning from Patients', 'Openness to
      Criticism', 'Negative Attitudes', 'Desire for Clear Guidelines', 'Peer Support',
      and 'Academic Approach'. Males scored significantly higher on 'Academic Approach'
      (P < 0.05). Each of the subscales reflects themes that permeate the atmosphere of
      general practice training. Further work is required to establish relationships
      between the subscales and the outcomes of learning and to explore the
      implications for continuing professional development. The questionnaire is an
      instrument that may prove useful in the future investigation of learning in
      general practice.

PMID- 8736193
TI  - An adolescent worried about his psoriasis.

PMID- 8736194
TI  - Progress in treating leukaemia.

PMID- 8736195
TI  - Advances in gynaecology.

PMID- 8736196
TI  - Review your reading: how to prepare for the CRQ paper.

PMID- 8736197
TI  - Managing hypoglycaemic emergencies.

PMID- 8736198
TI  - Do more diabetic patients need insulin?

PMID- 8736199
TI  - Dealing with the diabetic foot.

PMID- 8736200
TI  - What next in the treatment of diabetes?

PMID- 8736201
TI  - Indo-Asians with diabetes: a special case.

PMID- 8736202
TI  - Smoking cessation: professional problem or public policy?

PMID- 8736203
TI  - Does the treatment of cryptogenic fibrosing alveolitis influence prognosis?

PMID- 8736204
TI  - Patient-administered sequential spirometry in healthy volunteers and patients
      with alpha 1-antitrypsin deficiency.
AB  - The launching of cheap, pocket-sized spirometers, with data storage capability,
      has made patient-administered sequential spirometry (PASS) an attractive method
      of monitoring ventilatory capacity. At present, little information is available
      on the quality of PASS, compared to laboratory spirometry. The aim of this study
      was to investigate whether patients could perform PASS without loss of
      reliability and reproducibility as compared with traditional laboratory
      spirometry. Ten healthy volunteers performed spirometry for 1 month and 10
      emphysematous patients with alpha 1-antitrypsin deficiency (type PiZ) performed
      spirometry twice daily for up to 2 yr. To fulfil Good Clinical Practice criteria
      on full data documentation, a traditional direct recording spirometer, the
      Vitalograph R-model, was used. A decompression device was used for calibration
      and a 3.8% annual drift in volume registration was noted. This drift was largest
      for the first year. After training, all patients were able to perform
      unsupervised spirometry, producing technically correct forced expiratory curves.
      Reproducibility of FEV1 and FVC obtained by PASS was found to be as good as for
      laboratory spirometry. After adjustment for the diurnal variation, the residual
      variation of FEV1 was 2.5% (range 1.6-4.2%) for healthy volunteers and 5.6%
      (range 4.2-7.7%) for emphysematous patients. Forced vital capacity showed the
      same pattern. In conclusion, PASS is possible in highly motivated individuals
      without loss of reliability and reproducibility when compared to laboratory
      spirometry.

PMID- 8736205
TI  - Diagnostic value of transbronchial lung biopsy under fluoroscopic guidance in
      solitary pulmonary nodule in an endemic area of tuberculosis.
AB  - In the endemic area of tuberculosis, there are many cases that present
      tuberculosis as a solitary pulmonary nodule (SPN) on chest radiographs. The
      objective of this study is to evaluate the diagnostic yield of transbronchial
      lung biopsy (TBLB) under fluoroscopic guidance in SPNs such as lung cancer or
      pulmonary tuberculoma in areas with high prevalence of tuberculosis. One hundred
      and seventy patients with SPNs on chest radiographs were included in the study;
      all had negative sputum smears for tubercle bacilli and no malignancy by sputum
      cytology before bronchoscopy. Transbronchial lung biopsy and brushing were
      performed, routinely, under fluoroscopic guidance. Of 170 patients, 120 (70.6%)
      had lung cancer (including three with metastatic cancer), 40 (23.5%) patients had
      pulmonary tuberculosis (Tb), and the remaining 10 (5.9%) patients had other
      benign pulmonary lesions. The overall diagnostic rate in SPNs was 62.4% (106 of
      170). Transbronchial lung biopsy and brushing revealed a diagnostic sensitivity
      of 70.0% in lung cancer (84 of 120) and a sensitivity of 55% in Tb (22 of 40). In
      addition, TBLB and brushing also provided rapid microscopic identification of Tb
      in 18 of 40 patients (45%, including 15 by TBLB, one by brushing smear, and two
      by postbronchoscopic sputum). The percentage of positive diagnosis correlated
      with diameter of the SPN. Solitary pulmonary nodules with diameter less than 2 cm
      were diagnosed in only 35.3% of cases (6 of 17; cancer 40% vs. Tb 29%). In
      contrast, the diagnostic rates in SPNs with diameters 2-4 cm and greater than 4
      cm were 64.5% (78 of 121; cancer 72.0% vs. Tb 62.5%) and 68.8% of cases (22 of
      32), respectively. Diagnostic bronchoscopy under fluoroscopic guidance is a
      useful tool in evaluation of patients with a peripheral pulmonary nodule since it
      may provide additional information to minimize unnecessary thoracotomy and give
      way for proper medication as early as possible.

PMID- 8736206
TI  - Hyperventilation during exercise: independence on exercise-induced
      bronchoconstriction in mild asthma.
AB  - Ventilatory gas exchange during exercise was compared in patients with mild
      asthma (11 females and 11 males), hyperventilation syndrome (HVS, 11 females),
      and healthy subjects (11 females and 11 males) in order to assess
      hyperventilation during exercise and its association with exercise-induced
      bronchoconstriction. The asthmatics showed decreased working capacity and
      decreased maximal oxygen consumption, with no evidence of limitation due to
      impairment of ventilatory capacity. Ventilatory equivalents for CO2 and O2
      (VE/VCO2 and VE/VO2) at rest did not differ between the controls and asthmatics,
      but they were significantly elevated in HVS. In female asthmatics, ventilatory
      equivalents during exercise were significantly (P < 0.05) elevated compared with
      those of healthy subjects; in female controls, VE/VCO2 was 30.1 +/- 3.3 at low
      exercise and 27.4 +/- 6.5 at maximal exercise. In female asthmatics, the
      corresponding figures were 34.9 +/- 6.1 and 36.7 +/- 5.3. Furthermore, VE/VCO2
      individually related to percent of maximal oxygen consumption (VO2max) was
      significantly increased in female asthmatics both at low and high VO2. The
      highest ventilatory equivalents were obtained in HVS, 41.7 +/- 6.7 and 43.9 +/-
      0.9, respectively. Significant exercise-induced bronchoconstriction (decrease of
      FEV1 > 15%) was found in 50% of the asthmatics. The ventilatory equivalents did
      not correlate with exercise-induced changes in FEV1 (r2 < 0.3). Mild exercise
      induced hyperventilation which was observed in mild female asthmatics, did not
      appear to be related to exercise-induced bronchoconstriction.

PMID- 8736207
TI  - Detection of Pneumocystis carinii sequences in serum by polymerase chain
      reaction.
AB  - The clinical significance of the detection of Pneumocystis carinii DNA was
      evaluated, as well as the detection of circulating P. carinii antigen from serum
      using previously collected samples. Fourteen serum samples from 13 patients were
      diagnosed positively for P. carinii DNA by polymerase chain reaction (PCR). Ten
      of 14 episodes (71.4%) of pulmonary complications were compatible with P. carinii
      pneumonia. Two patients were definitely diagnosed as having had P. carinii
      pneumonia at autopsy. All patients positive for circulating antigens were also
      positive for P. carinii DNA, suggesting that the detection of P. carinii DNA by
      PCR is more sensitive compared to the detection of circulating antigens by the
      Ouchterlony method. It is concluded that the detection of P. carinii DNA in serum
      by PCR provides useful information for identifying P. carinii pneumonia.

PMID- 8736208
TI  - Hydrolytic enzyme of the alveolar macrophage in diffuse pulmonary interstitial
      disease.
AB  - Hydrolytic enzymes [acid phosphatase, beta-glucuronidase, beta-D-N-acetyl
      glucosaminidase (beta-D-NAGA), lysozyme and angiotensin-converting enzyme (ACE)]
      are the major constituents of alveolar macrophages (AM). These enzymes play a
      crucial role in the pathogenesis of interstitial lung diseases. Cell-associated
      activity of several enzymes in alveolar macrophages obtained from control
      subjects (n = 5) and patients suffering five representative types of interstitial
      pulmonary diseases [sarcoidosis (n = 10), extrinsic allergic alveolitis (n = 5),
      idiopathic pulmonary fibrosis (n = 5), neoplastic infiltration of the lung (n =
      5) and Pneumocystis carinii pneumonia (n = 5)] were evaluated. Cells were
      obtained by bronchoalveolar lavage and isolated by Ficoll-Hypaque gradient.
      Enzymatic activity was assessed by standardized tests. Bronchoalveolar lavage
      (BAL) lymphocyte counts were significantly elevated in the patients with active
      sarcoidosis (median: 57%), allergic extrinsic alveolitis (median: 51%) and
      neoplastic infiltration (median: 31%) as compared with the other groups, whereas
      BAL neutrophil and eosinophil counts were significantly elevated in the patients
      with idiopathic pulmonary fibrosis (neutrophil median: 29%; eosinophil median:
      3%). The highest alveolar macrophage enzymatic activities were obtained in the
      active sarcoidosis group (median ACE: 23.38 microKat 10(-6) AM; median lysozyme:
      8.64 nKat 10(-6) AM; median beta-glucuronidase: 324.22 U 10(-6) AM; median acid
      phosphatase: 0.78 nKat 10(-6) AM; median beta-D-NAGA: 1.85 nKat 10(-6) AM) which
      was significantly greater than in the control group (median ACE: 6.69 microKat
      10(-6) AM; median lysozyme: 1.95 nKat 10(-6) AM; median beta-glucuronidase: 39.88
      U 10(-6) AM; median acid phosphatase: 0.38 nKat 10(-6) AM; median beta-D-NAGA:
      0.44 nKat 10(-6) AM). However, intracellular lysosomal enzymatic activities of
      alveolar macrophages from patients with allergic extrinsic alveolitis, a disease
      in which the degree of alveolar macrophage activation is maximal, were similar to
      those of the control group. These findings demonstrated a different pattern of
      expression of alveolar macrophage's hydrolytic enzymes in lymphocytic diffuse
      pulmonary interstitial disease. In sarcoidotic patients, hydrolytic enzymes were
      increased whereas in allergic extrinsic alveolitis, hydrolytic enzyme activities
      were similar to control groups. Indirect data suggest that the release of
      lysosomal enzymes by alveolar macrophages during allergic extrinsic alveolitis
      may be a factor involved in the pulmonary lesions appearing in this disease.

PMID- 8736209
TI  - Amiodarone-induced bronchiolitis obliterans organizing pneumonia (BOOP).

PMID- 8736211
TI  - An autopsy case of diffuse panbronchiolitis accompanying rheumatoid arthritis.

PMID- 8736210
TI  - Acute, reversible pulmonary hypertension associated with cocaine use.

PMID- 8736212
TI  - Informed consent for bronchoscopy.

PMID- 8736213
TI  - New human light on bovine TB in cattle and wildlife?

PMID- 8736214
TI  - Distribution within the choroid of cholinergic nerve fibers from the ciliary
      ganglion in pigeons.
AB  - The distribution of the ciliary ganglion (CG) innervation to the pigeon choroid
      was determined immunohistochemically, using antisera against choline
      acetyltransferase (CHAT) and a neurofilament-related protein (the 3A10 antigen).
      Single-labeling revealed that the nerve fibers containing these two antigens were
      similarly distributed in the pigeon choroid, with the superior and temporal
      quadrants of the eye containing the most fibers. Both types of fibers surrounded
      and ramified on choroidal blood vessels. Additionally, CHAT+ varicosities were
      evident among vessels in the choroid and choriocapillaris. Double-label
      immunofluorescence revealed that CHAT and the 3A10 antigen were almost completely
      colocalized in choroidal nerve fibers, but absent from CHAT+ varicosities.
      Substance P-containing and calcitonin gene-related peptide-containing choroidal
      nerve fibers were poor in 3A10+ labeling. Transection of the postganglionic
      fibers of the CG reduced CHAT+ and 3A10+ nerve fibers in the choroid to 3-5% of
      normal abundance, with most of the residual fibers being located in the nasal and
      inferior quadrants. The present results suggest that the CG in pigeon
      preferentially influences choroidal blood flow in the superior and temporal parts
      of the eye, which are involved in high acuity and binocular vision.

PMID- 8736215
TI  - L-Glutamate-induced responses in OFF-type bipolar cells of the cat retina.
AB  - L-Glutamate (Glu)-induced current responses were studied in 119 isolated OFF-type
      bipolar cells of the cat retina. Cells were recorded by the patch clamp technique
      in the whole-cell configuration. Glu induced a current carried by alkali metal
      ions and divalent cations with a permeability ratio of PNa:PK:PCs:PCa =
      1:0.94:1.32:0.57. Sensitivity to Glu was highest in the dendritic region. Kainate
      and AMPA worked as potent agonists, but neither APB, L-aspartate, ACPD, nor NMDA
      (all at 100 microM) was effective. The Glu-induced response was antagonized by >
      1 microM CNQX. We inferred that OFF-type bipolar cells have a non-NMDA receptor
      channel that is permeable to alkali metal ions with low selectivity, but not NMDA
      receptor or metabotropic Glu receptor.

PMID- 8736216
TI  - Cholinergic effects on cat retina In vitro: changes in rod- and cone-driven b
      wave and optic nerve response.
AB  - To identify cholinergically mediated components in the optic nerve response (ONR)
      we studied effects of cholinergic agonists and antagonists in the arterially
      perfused cat eye. Acetylcholine, carbachol, scopolamine, quinuclidinylbenzilate
      and mecamylamine were applied intra-arterially in micromolar concentrations.
      Recordings of rod- and cone-driven ERG accompanied those of the ONR and revealed:
      (i) cholinergic agonists enhanced the b-wave, particularly under photopic
      conditions, whereas scopolamine decreased the b-wave. Mecamylamine induced
      biphasic effects (decrease followed by increase) in the amplitudes of the rod-
      and cone-driven b-waves. The effects on the cone-driven ERG were more marked than
      those on the rod-driven ERG. (ii) The ON-component of the ONR was increased, then
      decreased by acetylcholine. The cholinergic antagonists exerted complex changes
      in the ONR-ON component depending on dosage and adaptation. Scopolamine
      increased, then decreased the rod-driven ON-component, but mainly increased the
      cone-driven ON-component. Mecamylamine tended to increase the cone-driven, but to
      decrease the rod-driven ON-component of the ONR. (iii) The configuration of the
      rod- as well as for the cone-driven ONR, in particular the early plateau and OFF
      components, were consistently and reversibly changed by cholinergic agonists, as
      well as by both muscarinic and nicotinic antagonists. Agonists decreased, and
      antagonists increased the amplitude of the plateau-component. We conclude that
      the ERG b-wave was enhanced by acetylcholine, but decreased by cholinergic
      antagonists. Cholinergic agonists and antagonists affect the same specific
      components of the ONR in a dose-related and reversible fashion, indicating a
      major contribution of cholinergic mechanisms to information processing in the cat
      retina.

PMID- 8736217
TI  - Contrast discrimination at high contrasts reveals the influence of local light
      adaptation on contrast processing.
AB  - Previous measurements of contrast discrimination threshold, delta C, as a
      function of pedestal contrast, C, for sine-wave gratings have shown a power law
      relationship between delta C and C at suprathreshold levels of C. However, these
      studies have rarely used contrasts greater than 50%. Whittle (1986), using
      incremental and decremental patches, found that delta C increased with C only up
      to about 50%. At higher contrasts it decreased. Since a periodic stimulus can be
      considered to be composed of increments and decrements, we thought we might find
      such an inverse U-shaped function for gratings if we used contrasts up to 100%.
      We tested this for both sine-wave and square-wave stimuli at spatial frequencies
      from 0.0625 to 8.0 c/deg. We found that for frequencies up to 0.5 c/deg, delta C
      in nearly all cases 'dipped down' after about C = 50% contrast. At 4.0 and 8.0
      c/deg, however, no dip-down occurred. Additional experiments showed that the dip
      down was unlikely to be due to cortical long-term adaptation and most likely an
      effect of localized light adaptation to the dark bars. We argue that the absence
      of dip-down at high spatial frequencies was mainly due to the attenuation of
      contrast by the optics of the eye. As for the results of Whittle (1986), a
      Weber's Law in W = (Lmax-Lmin)/Lmin describes the inverse U-shaped contrast
      discrimination function well. Two other contrast expressions also linearize the
      data on log-log plots. We show how some familiar notions about the physiological
      operation of localized light adaptation can easily account for the form of the
      contrast discrimination function. Finally we estimate the number of discriminable
      steps in contrast from detection threshold to maximum contrast for the various
      spatial frequencies tested.

PMID- 8736218
TI  - Comments on "A multi-stage color model".
AB  - A critical review is offered for the article entitled 'A multi-stage color model'
      by De Valois and De Valois [(1993) Vision Research, 33, 1053-1065]. This letter
      discusses (i) related literature, (ii) substantive problems, and (iii) the topic
      of color/luminance confounding.

PMID- 8736219
TI  - Egocentric localization of a perisaccadic flash by manual pointing.
AB  - Reaching towards a visual object in the absence of visual referents relies on a
      chain of information, from the sensory signals encoding the object's image on the
      retina, to the motor signals driving the hand. One link in this chain is an
      extraretinal eye position signal (EEPS), which specifies the position of the eye
      in the head. EEPS must be updated in precise coordination with the eye's rapidly
      changing position, or perisaccadic visual targets will be mislocalized. There
      have been conflicting reports about the existence and nature of mislocalizations
      associated with saccades. We measured perisaccadic visual localization by
      presenting brief (250 microseconds), bright (6000 cd/m2), binocular, gaze-point
      (foveal) probe flashes in an otherwise dark field to normal human subjects
      instructed to point to them with an unseen hand. Saccade and fixation targets
      were auditory, making intravisual comparison impossible. Saccades, elicited
      randomly to left and right of straight ahead, had a mean magnitude of 8.9 deg.
      Control trials, employing only non-perisaccadic probes and providing feedback of
      pointing errors, were randomly interspersed, to monitor and control drift of hand
      eye coordination. On average, localization began to shift for probes presented 2
      msec after the eye began to move, reaching a stable post-saccadic value with time
      constant tau = 71 msec. A second experiment was similar, except that viewing was
      monocular, and probes were presented randomly, at gaze (on fovea), 6 deg left of
      gaze (right of fovea) and 6 deg right of gaze (left of fovea). The main analysis
      treated saccades larger than 8 deg: their mean magnitude was 12.9 deg. Flashes
      left of gaze were relocalized faster (tau = 65 msec) than flashes right of gaze
      (tau = 129 msec) around the time of leftward saccades. In contrast, flashes right
      of gaze were relocalized faster (tau = 62 msec) than flashes left of gaze (tau =
      90 msec) around the time of rightward saccades. Time constant was independent of
      saccade size. Updating began for probes presented within 4 msec of the beginning
      of saccades, and was not a function of saccade or flash direction. Thus, there
      were no systematic mislocalizations of probes presented before eye movement, and
      large mislocalizations of probes presented during and after. Mislocalizations
      were, on average, always in the direction opposite the saccade, and were maximal
      (about half the magnitude of the completed saccade) near the end of the saccade.
      Stable post-saccadic localization was not achieved until about 100-300 msec after
      completion of a saccade; EEPS was updated slowly, compared to eye position
      itself. The visual field was not remapped uniformly: the side that would normally
      contain the target of a visually evoked saccade (and usually the target of a
      corrective saccade), was updated with a shorter time constant.

PMID- 8736220
TI  - Dynamical version--vergence interactions for a binocular implementation of
      Donders' law.
AB  - Recent investigations of the three-dimensional (3D) binocular eye positions in
      near vision have shown that a full characterization of vergence requires
      incorporation of its torsional component. The latter has a proportional
      relationship with horizontal vergence and elevation, causing the eyes to have
      intorsion in near upgaze but extorsion in near downgaze. In this study, we focus
      on the dynamical implementation of the torsional vergence component in both pure
      vergence and combined direction-depth binocular eye movements. We report on
      experiments in five subjects whose eye movements were recorded binocularly with
      the 3D magnetic search-coil technique. In pure vergence movements at a given
      elevation, torsional vergence increased with almost the same time course as
      horizontal vergence. In addition, the dynamic relationships among torsional
      vergence, horizontal vergence and elevation were close to static results in all
      subjects. In combined direction-depth movements a similar relationship held for
      the complete movements, but we could not firmly establish a straight-line
      relationship during the saccadic portion of the movement. Possible factors
      determining these responses are discussed. We computed the angular velocity
      profiles of pure vergence movements to see how tilting of the vergence angular
      velocity axis relative to Listing's plane generates torsional vergence. It is
      widely held that both saccadic and vergence movements are controlled by dedicated
      pulse generators specifying velocity signals. Little thought has been given to
      the question of how these controllers can be coordinated to yield realistic eye
      movements in 3D. Our finding that this tilt was close to full-angle, suggests a
      model in which version and vergence velocity signals are combined before the 3D
      neural integrator proposed by Tweed and Vilis. The implications of this scheme
      for the control of binocular eye movements in three dimensions are discussed,
      along with possible neural correlates.

PMID- 8736221
TI  - Contribution of area MT to perception of three-dimensional shape: a computational
      study.
AB  - Successful recognition and manipulation of objects in one's visual environment is
      critically dependent upon the ability to recover three-dimensional (3D) surface
      geometry from two-dimensional (2D) retinal images. The relative motion of image
      features, caused by relative displacement of object and observer, has
      characteristic properties that betray components of the 3D source geometry
      (distance, tilt, slant and curvature) and is among the most valuable sources of
      information used for 3D surface recovery by the primate visual system. We have
      considered the behavior of motion-sensitive neurons in primate visual cortex and
      found that their properties closely resemble those of differential motion
      operators that can be used to formally characterize the 3D shape of a smooth
      moving surface. Our analysis has led us to identify a set of three orders of
      filters for differential motion detection. These filters behave in a manner that
      is strikingly similar to the spatial and velocity tuning profiles of a sub
      population of neurons--those possessing antagonistic motion surrounds--in the
      middle temporal visual area (MT). On the basis of this analysis, we suggest that
      MT neurons subserve 3D surface recovery from relative motion cues.

PMID- 8736222
TI  - Sites of disease action in a retinal dystrophy with supernormal and delayed rod
      electroretinogram b-waves.
AB  - Delayed rod ERG b-waves in patients with an unusual retinal dystrophy have been
      attributed by some to an abnormality in receptor cGMP activity. Here the sites of
      disease action are studied by analyzing rod and cone ERGs using new analytical
      methods and a wide range of stimulus intensities. Consistent with previous
      reports, the five patients studied showed rod b-waves that were normal or
      supernormal in amplitude in response to intense flashes, but smaller than normal
      and markedly delayed in response to weaker flashes. The cone ERGs, recorded to 29
      Hz flicker and to flashes upon a background, were smaller than normal and also
      showed delays. Models of phototransduction fitted to rod and cone a-waves
      indicated that the delays in the rod and cone b-waves were not due to the speed
      or amplification of the transduction process. An analysis of the derived inner
      nuclear layer (INL) response suggests that the sites of disease action are beyond
      the outer segment and involve a delay in the activation of INL activity.

PMID- 8736223
TI  - Spatial frequency sweep pattern reversal VER acuity vs Snellen visual acuity:
      effect of optical defocus.
AB  - The effect of artificially induced image defocusing on visual acuities (VAs)
      measured by spatial frequency sweep pattern reversal visual evoked response
      (SPVER) and Snellen measurement was studied in six normal subjects. The steady
      state SPVER was recorded using vertical gratings of 10 different spatial
      frequencies ranging from 0.52 to 30.36 c/deg. The SPVER acuity was compared with
      Snellen acuity (SA) measured under the same conditions of optical defocus. With
      moderate defocusing [< + 1.0 diopter (D), VA > 20/40], the SPVER acuities were
      equal to or poorer than the SAs. With more defocus (> + 1.5 D, VA < 20/70), the
      SPVER acuities became better than the SAs. The discrepancies between the SA and
      SPVER acuities may be the result of the influence of the parafoveal area on the
      SPVER at lower visual acuity levels.

PMID- 8736224
TI  - Ultrasonographic diagnosis of congenital portosystemic shunt in 14 cats.
AB  - Twenty-four cats with clinical and, or, clinicopathological signs compatible with
      portosystemic shunting were examined prospectively using two-dimensional grey
      scale, duplex and colour-flow Doppler ultrasonography. Diagnosis of congenital
      portosystemic shunt was subsequently confirmed in 14 cats using operative
      mesenteric portography and surgery. Of the 14 affected cats, nine were purebred;
      eight were male and six female. The mean age at the time of diagnosis was nine
      months (range four to 27 months). Ultrasonographic evidence of a small liver was
      present in seven cats (50 per cent); visibility of intrahepatic portal vessels
      was reduced in three (21 per cent). An anomalous blood vessel was identified
      ultrasonographically in each cat; in 10 cats (71 per cent) the vessel was
      observed to originate from the portal vein and drain into the caudal vena cava.
      Abnormally variable portal blood flow was present in eight of the 10 cats in
      which it was measured. At surgery, six shunts were intrahepatic and eight
      extrahepatic; the ultrasonographic diagnosis of intra- versus extrahepatic shunt
      was correct in 13 cats (93 per cent). No anomalous blood vessels or abnormalities
      affecting the portal vein were detected ultrasonographically in any of the 10
      cats that did not have congenital portosystemic shunting. Hence, the accuracy of
      ultrasonography for diagnosis of congenital portosystemic shunting in this series
      was 100 per cent.

PMID- 8736225
TI  - Practical use of a combination of a dopamine agonist and a synthetic
      prostaglandin analogue to terminate unwanted pregnancy in dogs.
AB  - The combination of a dopamine agonist, cabergoline, and a synthetic analogue of
      prostaglandin F2 alpha, cloprostenol, was used to induce termination of pregnancy
      from day 25 after the estimated luteinising hormone surge (day 27 +/- 4 after the
      first mating) in five mature beagle bitches. Cabergoline was administered orally
      at 5 micrograms/kg daily and cloprostenol was injected subcutaneously at 1
      microgram/kg every other day. Treatment efficacy, in terms of pregnancy
      termination, was 100 per cent. Termination always took place by resorption of the
      fetuses. No side effects were observed. A mean of three injections of
      cloprostenol and nine days of cabergoline treatment was necessary to eliminate
      all signs of gestation. Termination was in each case accompanied by a decline in
      plasma progesterone (to less than 1 ng/ml) within 72 hours of initiation of
      treatment. In a control group of five, untreated bitches, plasma progesterone
      remained elevated throughout a corresponding period (from day 25 to day 50 after
      the estimated luteinising hormone surge). In the treated group, interoestrous
      intervals (98 +/- 41 days) were reduced, compared with previous cycles (194 +/- 9
      days) or with those of the control animals (205 +/- 37 days). It is concluded
      that the combination treatment with the anti-prolactinic agent, cabergoline (5
      micrograms/kg/day), and the synthetic prostaglandin F2 alpha, cloprostenol (1
      microgram/kg/two days), is an easy, practical, reliable and safe method to
      terminate pregnancy near and before mid-gestation in dogs.

PMID- 8736226
TI  - Pleural effusion in cats: 82 cases (1987 to 1995).
AB  - Eighty-two cases of feline pleural effusion were identified and reviewed to
      assess the type of fluid, underlying disease process, predisposing conditions,
      historical and physical examination findings, laboratory and cytology data,
      response to treatment and outcome. Pertinent findings included a high occurrence
      of pleural effusion with mediastinal lymphoma (and other types of intrathoracic
      neoplasia), pyothorax, cardiomyopathy and feline infectious peritonitis virus
      infection. Sixteen cases, eight with chylous effusion, had no underlying disease
      identified. Cats with pyothorax and effusion secondary to trauma had the best
      prognosis for complete recovery. Otherwise, the outcome was variable and the
      prognosis was guarded to poor.

PMID- 8736227
TI  - Fibro-cartilaginous embolism in a cat.
AB  - A nine-year-old cat was presented with a history of an acute onset of paraplegia.
      On the basis of the neurological examination, the lesion was localised between
      the fourth lumbar and third sacral segments (L4 to S3) of the spinal cord.
      Investigations included radiography, myelography, cerebrospinal fluid analysis,
      routine haematology and biochemistry, feline leukaemia virus testing and
      urinalysis. A definitive diagnosis was not achieved and the cat was euthanased 12
      days after presentation. Post mortem examination revealed infarction of the
      spinal cord secondary to fibrocartilaginous embolisation. This is the first
      reported case of fibrocartilaginous embolism in the cat in the UK.

PMID- 8736228
TI  - Fracture of the humerus after cancellous bone graft harvesting in a dog.
AB  - A five-year-old male Shetland sheepdog underwent calcaneoquartal arthrodesis for
      instability of the proximal intertarsal joint. A cancellous bone graft was
      harvested from the proximal humerus and packed around the arthrodesis site.
      Twenty-four hours postoperatively the dog developed a non-weightbearing forelimb
      lameness. Clinical and radiographic examination revealed a fracture of the
      humerus through the hole used to obtain the graft. Surgical repair of the
      fracture led to an uneventful recovery.

PMID- 8736229
TI  - Uterine serosal inclusion cysts in a bitch.
AB  - A six-year-old, pluriparous German shepherd dog bitch was presented with an
      abnormal vaginal discharge of several weeks' duration. Clinical signs and
      radiographic and ultrasonographic findings supported an initial diagnosis of
      segmental cystic endometrial hyperplasia, and ovariohysterectomy was performed.
      Macroscopically, the uterus appeared normal except for one large and several
      smaller cysts attached to its antimesometrial side. These cysts were restricted
      to a small area of the left uterine horn. The histological diagnosis was serosal
      inclusion cysts. The clinical findings, gross pathology and histopathology are
      described and discussed.

PMID- 8736230
TI  - Cytogenetic findings in two cases of feline histiocytoma.

PMID- 8736231
TI  - Maxillectomy and targeted radionuclide therapy with 153Sm-EDTMP in a recurrent
      canine osteosarcoma.
AB  - An eight-year-old dog with a local relapse of an osteosarcoma was treated with
      partial maxillectomy and systemic radionuclide therapy that involved two
      injections, 43 and 45 megabecquerels per kg bodyweight of the bone-seeking agent
      samarium-153-ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP), 15
      weeks apart. A transient drop in white blood cell count and platelet count was
      observed following each 153Sm-EDTMP treatment. Follow-up 21 months after surgery
      revealed no evidence of local recurrence or metastases. The dog was in excellent
      condition, suffering only minor sequelae from the surgical procedure. Compared
      with historical controls treated with surgery alone, the combination of surgery
      and systemic radionuclide therapy seems a promising strategy for the treatment of
      canine osteosarcoma.

PMID- 8736232
TI  - A taste of the exotic at Birmingham.

PMID- 8736233
TI  - Progress in pawprinting.

PMID- 8736234
TI  - Replication of hepatitis C virus.
AB  - The mode of replication of the hepatitis C virus (HCV) remains poorly understood.
      Attempts to produce a tissue culture model containing replicating HCV have been
      largely unsuccessful. Recent studies on sera from patients chronically infected
      with HCV have shown that viral particles may be found in high- or low-density
      fractions. High-density fractions contain non-infectious virions whilst
      infectious particles can be derived from low-density material. Using appropriate
      infectious fractions we have successfully infected a number of human cell lines
      allowing studies of HCV replication to be initiated.

PMID- 8736235
TI  - Visualization of hepatitis C virions and putative defective interfering particles
      isolated from low-density lipoproteins.
AB  - Hepatitis C virus (HCV) in highly infectious sera has been shown to be
      predominantly associated with low-density lipoproteins. To determine whether the
      association is specific to low-density lipoproteins (LDL) or very low-density
      lipoproteins (VLDL), we fractionated HCV-containing plasma by a column
      chromatographic procedure known to separate these classes. Hepatitis C virus RNA
      detected by polymerase chain reaction (PCR) was associated primarily with the
      very low-density (VLDL) fraction. However, it could not be ruled out that virus
      associated LDL may have eluted with this fraction. Hepatitis C virus virions
      isolated from sera having sufficient titre for visualization by electron
      microscopy are generally coated with antiviral antibodies, therefore we utilized
      the lipid association to isolate antibody-free virions. Very low-density
      lipoproteins were isolated by ultracentrifugal flotation and then treated with
      deoxycholate to release the virions. These were then isolated in a highly
      purified form by centrifugation in a sucrose gradient. The 1.10-1.11 g ml-1
      region of the gradients contained 60-70 nm particles. Particles with similar
      surface structure but having a diameter of only 30-40 nm constituted about 30% of
      the total. The latter may represent defective interfering particles. The identity
      of both small and large particles with HCV virions and associated particles was
      confirmed by their trapping on grids by an anti-HCV E2 monoclonal antibody, and
      by their aggregation by rabbit antiserum to an amino-terminal peptide of E1.
      Thus, both E1 and E2 epitopes are displayed on the surface of intact HCV virions.

PMID- 8736236
TI  - In vivo inhibition of hepatitis B viral gene expression by antisense
      phosphorothioate oligodeoxynucleotides in athymic nude mice.
AB  - Antisense oligodeoxynucleotides strategies have been used both to study normal
      gene function and to block gene expression therapeutically. We have previously
      shown that a number of antisense oligonucleotides against hepatitis B virus (HBV)
      mRNA are able to inhibit viral gene expression in vitro. Here we report the
      establishment of an animal model producing HBV markers in athymic nude mice and
      inhibition of HBV gene expression and replication by antisense DNA in vivo.
      2.2.15 cells (Hep-G2 cell line transfected with HBV genomes) were injected
      subcutaneously (s.c.) into athymic BALB/c nude mice at a total cell number of 0.5
      1 x 10(8) per mouse. Transplanted tumours developed about 2 weeks after
      inoculation. Hepatitis B surface and e antigens (HBsAg and HBeAg), as well as HBV
      DNA, could be detected in the circulation of tumour-bearing mice. Hepatitis B
      surface antigen and hepatitis B core antigen (HBcAg) were demonstrated in tumour
      cells. After 10 days of tumour growth, antisense phosphorothioate
      oligonucleotide, complementary to the cap site of the SP II promoter of HBV mRNA,
      were injected by infiltration into or around the tumour as a daily dose of 20
      micrograms per gram body weight. Treatment for a total of 10 days resulted in an
      effective inhibition of viral replication and gene expression. These results
      suggest therapeutic potential for antisense oligomers in the treatment of
      patients who are chronically infected with HBV.

PMID- 8736237
TI  - Interferon accumulation in cirrhotic rat liver.
AB  - In patients with chronic hepatitis C, the therapeutic effect of interferon (IFN)
      is influenced by the progression of liver disease. In a previous study, we showed
      that 2',5'-oligoadenylate synthetase activity in the liver homogenate was
      significantly lower in cirrhotic rats than in controls after injection of murine
      IFN. To determine the reason for this decrease, we injected IFN into rats with
      thioacetamide-induced cirrhosis and used microautoradiography with human
      lymphoblastoid interferon ([125I]LyIFN). Accumulation of [125I]LyIFN in cirrhotic
      rat livers was approximately half of that in control rats (2880 +/- 900 vs 5770
      +/- 600 mm2, P < 0.01). In the cirrhotic rat livers there were few grains on the
      hepatocytes, but many on collagen fibres. These results suggest that binding of
      IFN to its hepatocyte receptors is hindered in the presence of cirrhosis. The
      decreased amount of IFN reaching hepatocytes may contribute to the poor responses
      to IFN seen in patients with cirrhosis.

PMID- 8736238
TI  - Absence of double-stranded replicative forms of HCV RNA in liver tissue from
      chronically infected patients.
AB  - The mechanism of hepatitis C virus (HCV) replication is unknown, although the
      classification of HCV in the Flaviviridae has led to the postulation that HCV may
      adopt a replication strategy similar to that of the flaviviruses. To determine if
      HCV double-stranded replicative forms, consistent with this strategy, were
      present in total liver RNA extracted from HCV-infected individuals, HCV-specific
      RNA was detected by reverse transcription followed by polymerase chain reaction
      (RT-PCR). Initially, a strand-specific RT-PCR resulting from chemical
      modification of the 3' end of the RNA was established using in vitro transcribed
      HCV RNA. This procedure allowed the specific detection of positive and negative
      HCV RNA strands in HCV-infected liver tissue. The species of HCV RNA was then
      examined in RNA extracted from liver tissue from naturally infected individuals;
      total liver RNA was either: (i) fractionated with 2M LiCl (designed to
      precipitate single-stranded and partially double-stranded RNA); or (ii) digested
      with RNase A in high salt conditions (designed to digest single-stranded RNA
      only). Amplification of positive sense HCV RNA from the LiCl-insoluble fraction,
      but not from the LiCl-soluble fraction nor in the RNase A-digested sample, was
      consistent with the interpretation that single-strand, but not double-stranded
      HCV RNA, was contained in the liver samples. Thus, it is unclear if a double
      stranded RNA species is formed during the HCV replication cycle.

PMID- 8736239
TI  - Reactogenicity and immunogenicity of a new recombinant hepatitis B vaccine
      containing Pre S antigens: a preliminary report.
AB  - A new vaccine against hepatitis B virus (HBV) infection, produced in mammalian
      Chinese hamster ovary (CHO) cells, contains the small(s), middle (Pre S2) and
      large (Pre S1) surface proteins of HBV. Three injections of a 5-micrograms or 10
      micrograms dose were administered intramuscularly (i.m.) at 0, 1 and 6 months to
      a group of 105 young adults, who were monitored for a period of 6 months after
      the third injection. Seroconversion rates were 100% after the second injection of
      the 5-micrograms or 10-micrograms dose. Geometric mean titres of HBsAb at 1 month
      after the third injection were 12,156 mIU ml-1 and 13,482 mIU ml-1 in those
      receiving the 5-micrograms and 10-micrograms dose respectively. The vaccine was
      well tolerated with no significant adverse events. These preliminary results
      suggest that the Pre S-s recombinant vaccine, produced in mammalian cells, is
      highly immunogenic, leading to 100% seroconversion in the population tested after
      injection of only two doses of 5 micrograms.

PMID- 8736240
TI  - Longitudinal genotype analysis and quantification of hepatitis C virus in
      haemophilic patients receiving interferon-alpha therapy.
AB  - Haemophilic patients have a high prevalence of hepatitis C virus (HCV) infection
      because of the use of unsterilized clotting factor concentrates. Six major
      genotypes of HCV have been distinguished so far, with epidemiological evidence
      suggesting that genotypes 1-3 are common in the indigenous UK and US populations.
      The aim of this study was to analyse the changes in viral load and composition of
      the HCV quasispecies in haemophilic patients receiving therapy with interferon
      alpha (IFN-alpha) using the four major methods currently available for HCV
      genotyping. The most consistent genotype results were obtained using restriction
      fragment-length polymorphism (RFLP) analysis when compared with the DNA sequence
      analysis, and showed that the dominant genotype can change in patients with mixed
      genotype infections treated with IFN-alpha. This study indicates the difficulties
      in studying this group of patients with mixed HCV genotype infections, and that
      frequent sampling is necessary, together with viral load measurement to monitor
      response to IFN-alpha therapy.

PMID- 8736241
TI  - Medical education in community sites.

PMID- 8736242
TI  - The Calgary-Cambridge Referenced Observation Guides: an aid to defining the
      curriculum and organizing the teaching in communication training programmes.
AB  - Effective communication between doctor and patient is a core clinical skill. It
      is increasingly recognized that it should and can be taught with the same rigour
      as other basic medical sciences. To validate this teaching, it is important to
      define the content of communication training programmes by stating clearly what
      is to be learnt. We therefore describe a practical teaching tool, the Calgary
      Cambridge Referenced Observation Guides, that delineates and structures the
      skills which aid doctor-patient communication. We provide detailed references to
      substantiate the research and theoretical basis of these individual skills. The
      guides form the foundation of a sound communication curriculum and are offered as
      a starting point for programme directors, facilitators and learners at all
      levels. We describe how these guides can also be used on an everyday basis to
      help facilitators teach and students learn within the experiential methodology
      that has been shown to be central to communication training. The learner-centred
      and opportunistic approach used in communication teaching makes it difficult for
      learners to piece together their evolving understanding of communication. The
      guides give practical help in countering this problem by providing: an easily
      accessible aide-memoire; a recording instrument that makes feedback more
      systematic; and an overall conceptual framework within which to organize the
      numerous skills that are discovered one by one as the communication curriculum
      unfolds.

PMID- 8736243
TI  - Teaching and learning clinical perception.
AB  - A central task in clinical teaching is organization of the students' experience
      in clinical perception--the ability to observe, to recognize, to discriminate and
      to interpret clinical evidence. We cannot teach sensory perceptual experience.
      Students must experience the clinical phenomena for themselves. But we can ensure
      that what the student experiences is most likely to be turned into clinical
      learning. This paper dissects the learning task in order to derive plans for
      teaching clinical perception. A major purpose is to encourage closer study of
      physical examination, which has largely been upstaged by investigations. Students
      learn inductively from their experiences of examining patients, cumulating a
      'clinical memory' of images of patients with diseases. Reflection on that
      experience with the clinical teacher translates the sensory evidence into words.
      Teachers link the clinical observations of 'disease in patients' with previously
      learned images of 'diseases in organs', to ensure that clinical features and
      underlying basic science knowledge are clearly integrated. Perception is an
      active process, not a passive reception of observational data. Learning and
      teaching clinical perception uses both the student's direct 'sense' experiences
      and the teacher's guidance in 'making sense' of them.

PMID- 8736244
TI  - Disease prevention and health promotion: a study of medical students and
      teachers.
AB  - All students at the Royal Free Hospital School of Medicine (n = 508) were
      surveyed on their self-reported smoking and drinking habits, attitudes to disease
      prevention and health promotion in general, attitudes towards the teaching of
      disease prevention and health promotion, and their perception of what was taught
      at the beginning of the 1993-1994 academic year (response rate 75.2%). The
      teaching staff (n = 271) were also surveyed on their attitudes towards the
      teaching of disease prevention and health promotion, and their perception of what
      was taught (response rate 74.2%). Seventeen per cent of the students reported
      they were current smokers and 81% drank alcohol. Four factors were extracted from
      the responses to the items on disease prevention and health promotion in general
      and these represented the importance of health, a patient-centred approach,
      patient responsibility and a doctor-centred approach. Clinical students and those
      who were older were more likely to have a 'patient-centred' approach to disease
      prevention and health promotion. Sixty per cent of clinical and 44% of pre
      clinical teachers aimed to teach about disease prevention and health promotion.
      The topics reported by students as most likely to have been taught in detail are
      smoking and health, alcohol and health, immunization, and breast and cervical
      screening. However, all these topics were reported as having been taught in
      detail by less than 50% of the students. The majority of students and teachers
      believe that teaching about disease prevention and health promotion should be
      integrated into all years of the curriculum and all clinical firms. Teachers were
      significantly less likely than students to believe that students should learn
      more about disease prevention and health promotion, and that learning about
      prevention is as important as learning about diagnosis and treatment. We believe
      that, in order to build on the positive features highlighted in this study,
      agreed aims and objectives should be developed and teaching about disease
      prevention and health promotion should be integrated both horizontally and
      vertically throughout the curriculum.

PMID- 8736245
TI  - The use of student journals in problem-based learning.
AB  - This paper describes several examples of the use of journals in a Bachelor of
      Dental Surgery course. The examples cover: the use of journals in first year
      subjects and in later-year clinical subjects; the effect of changes in policy and
      practise as a result of experience with journals; and student views on their
      experiences with journals. The use of journals offers a means of achieving some
      of the more important goals of problem-based learning (PBL), particularly those
      requiring students to reflect upon and evaluate their experiences. When
      effectively integrated in a PBL course, journals have several functions: to
      formalize reflection; an outlet for personal feeling; an opportunity for feedback
      about a student's progress and about the course; to provide the student with a
      summary of the year's work; and a means whereby students and teachers gain
      insight into the learning process. However, our experience in Dentistry raises
      several contentious issues, especially with regard to confidentiality and
      assessment. We make several recommendations for the effective use of journals
      based on the need for frequent communication between students and staff, the
      development of an environment of trust, and the need for staff and student
      education in journal use.

PMID- 8736246
TI  - An information technology course in the medical curriculum.
AB  - This paper concerns the information technology course now running in year 1 of
      the undergraduate curriculum of the medical school of Leeds University. The
      background and objectives of the course are described, and the course content is
      outlined in terms of knowledge and practical skills. By the end of the course,
      95% of students could successfully accomplish 95% of the skill tasks taught. As
      regards attitudes to IT, independent studies comparing two randomly selected
      groups suggested students who had taken the course (a) used IT more frequently,
      and (b) viewed IT more favourably than their counterparts.

PMID- 8736247
TI  - Consulting skills training and medical students' interviewing efficiency.
AB  - In more traditional medical education, medical students took a patient's medical
      history by asking a series of sequenced, routine questions, covering presenting
      medical problem(s); medical history; social and personal history; systems review;
      and physical examination. Following this process, the student then attempted to
      derive the patient's medical problems. This inductive problem-solving paradigm
      may not assist students to prepare for their future interviewing needs, given
      doctors use a hypothetico-deductive, problem-solving approach when interviewing
      patients and numerous researchers have developed specialized communication skills
      training programmes designed to enhance students' interviewing skills. Students
      given specific consulting skills training have tended to show significantly
      greater interpersonal effectiveness and improved interview behaviours compared
      with students who experience traditional patient clerking training. These
      improvements in interviewing tend to persist over the period of students' medical
      training. The aim of the present study was to determine whether specialized
      communication skills training helped students elicit greater quantity and quality
      of information from patients and if so, whether such information assisted
      students in improving their diagnostic skills. Videotaped history-taking
      interviews conducted by students trained in communication skills and untrained
      (control) students were rated for their interview efficiency. A comparison of
      ratings given by experimentally naive, independent observers revealed that
      trained students were more efficient, but took no longer than their control group
      counterparts to elicit fuller, more relevant information. However, the student
      groups did not differ in the accuracy or scope of their medical diagnoses. It is
      argued that students' lack of medical knowledge in this early phase of their
      clinical training militated against their being able to use their interviewing
      competence to derive more potentially accurate medical diagnoses.

PMID- 8736249
TI  - Training medical students in HIV/AIDS test counselling: results of a randomized
      trial.
AB  - The study assessed the effectiveness of a programme aimed at increasing medical
      students' skills in counselling patients presenting for HIV testing/AIDS
      information. Senior medical students were randomly assigned to receive a short
      course in pre- and post-test counselling, or to a control group which received
      the usual curriculum. The students' performance in counselling simulated patients
      was videotaped at baseline and after 3 months. A subsample was also assessed at
      12 months. Students receiving the programme showed significantly greater
      improvement in pre- and post-test counselling skills over 3 months than did the
      controls. For the sub-sample continuing to 12 months, a significant effect over
      time was found; however, there was no significant difference between the groups.
      This may have been influenced by the small sample sizes used for the 12-month
      assessment. General interactional skills improved for the over-all sample over 3
      and 12 months, but again there were no significant differences between groups.
      Those exposed to the programme did not show significantly greater changes in
      either knowledge or attitude scores over either time frame, compared with
      controls. When taught in addition to the usual undergraduate curriculum at
      Newcastle University, this short interactional skills course significantly
      enhanced students' ability to provide pre- or post-test counselling for HIV/AIDS.

PMID- 8736248
TI  - Interprofessional clinical education of medical and pharmacy students.
AB  - Pharmacists have become increasingly involved in influencing prescribing.
      Pharmaceutical education has changed accordingly, with increased teaching in
      therapeutics, partly on hospitals wards, giving students an insight into diseases
      and helping communication with clinicians. To extend this idea we have designed
      joint therapeutics teaching sessions with pharmacy and medical students. The
      scheme involves final year pharmacy students who have completed a course in
      clinical pharmacy and medical students who have completed their second MB.
      Interdisciplinary pairs of students are assigned a patient with common medical
      and therapeutic problems, such as arthritis, diabetes and cardiac failure;
      patients on multiple drug treatments are preferred. They jointly obtain a
      history: the medical student performs basic clerking, while the pharmacy student
      obtains the medication history. The medical student subsequently presents a brief
      medical history, with a summary of the patient's current problems. For each
      problem, the pharmacy student presents the current therapy, its rationale and how
      it is to be monitored. Experience with 73 students over 3 years has shown that
      almost all found sessions with students from another discipline useful. Few felt
      that members of the pairs contributed unequally. The main problem appeared to be
      insufficient time (although 2 1/2 h were allowed). Most students favoured more
      such sessions. Little difference in ability appeared between the two disciplines;
      there was considerable co-operation and little nascent 'professional rivalry'.
      The medical students were more comfortable interviewing patients, and the
      pharmacy students more confident analysing drug therapy. It is concluded that
      such interdisciplinary sessions are a successful method of clinical teaching and
      should be encouraged.

PMID- 8736250
TI  - Library use and academic achievement among medical students.
AB  - Many factors play a part in determining the performance of students in
      examinations, but the extent to which students use library facilities does not
      appear to have been recently considered as a factor, in medicine or in any other
      academic subject. In this study, the number of books borrowed from the library by
      undergraduate medical students was used as a simple measure of library use, and
      significant differences in book-borrowing levels were found between students in
      different years of the medical course, students from different regions of the
      world, and men and women students. In the first year of the course, students who
      borrowed most also performed best in their end-of-year examinations, and this
      association was only partly explained by regional differences. No such
      association was found among final-year students, suggesting different study
      habits and different assessment criteria in the clinical years of the course.

PMID- 8736251
TI  - Leeds Undergraduate Medical Education Conference, 7-8 July 1995.
AB  - The Leeds Undergraduate Medical Education Conference (LUMEC) was held on 7-8 July
      1995. This conference, devoted entirely to undergraduate medical education, was
      unique in that it was organized entirely by four medical students. It attracted a
      wide and enthusiastic audience and excellent speakers. Professor Charles George
      (Chairman, Education Committee, General Medical Council) spoke about Tomorrow's
      Doctors, Dr Mark Bailey (Part-chairman, Medical Students' Committee of the
      British Medical Association) responded with 'Today's Students on Tomorrow's
      Doctors', and Dr Fleur Fisher (Ethics, Science and Information Division, British
      Medical Association) focused on the central place of ethics and communication
      skills in medicine. Professor Sam Leinster (Director of Medical Studies,
      Liverpool University) and Professor Tim de Dombal (Director, Clinical Information
      Science Unit, Leeds University) debated the need for new technology and radical
      change in the curriculum. Finally, Dr Stella Lowry (International Division,
      British Medical Association) considered the assessment of staff and Mrs Joy
      Crosby (Curriculum Facilitator, Dundee Medical School) discussed the assessment
      of students. Discussions focused on a variety of areas, including the need for
      change, the control of the money available for teaching and the problems of
      assessment.

PMID- 8736252
TI  - The time course of adaptation in macaque retinal ganglion cells.
AB  - The time course of adaptation of cells of the parvocellular (PC) and
      magnocellular (MC) pathways has been characterized following changes in retinal
      illuminance or chromaticity. Adaptation state was cycled between high and low
      luminance levels or between backgrounds with wavelengths metameric to 630 and 570
      nm. Cell responsivity was probed with brief bursts of luminance or chromatic
      modulation. After a change in luminance, adaptation of both MC-cells (tested with
      a luminance probe) and red-green PC-cells (tested with a chromatic probe) was
      relatively rapid and largely complete within 100 msec or less. After a change in
      chromaticity, recovery of responsivity in red-green PC-cells was dependent on
      cell type. Recovery of responsivity with backgrounds elevating maintained firing
      was complete within a few seconds, but with backgrounds suppressing cell firing,
      recovery took many tens of seconds. This very slow time course may be due to a
      threshold effect. In experiments with backgrounds which selectively adapted one
      cone type, use of cone-isolating probes indicated that the time course of PC-cell
      chromatic adaptation may be determined at a site after the subtraction of cone
      signals. Recovery of responsivity of MC-cells was also prolonged over several
      seconds following a chromatic change. Our data suggest that adaptation in macaque
      ganglion cells depends on mechanisms both before and after the site of cone
      interaction, and that these mechanisms may differ in time course between MC- and
      PC-cells. The results indicate that it may be important in psychophysical
      adaptation experiments to consider the presence of multiple postreceptoral
      mechanisms with different adaptation characteristics.

PMID- 8736253
TI  - Molecular cloning and characterization of the putative ultraviolet-sensitive
      visual pigment of goldfish.
AB  - A cDNA full length encoding a putative ultraviolet (UV)-sensitive visual pigment
      of goldfish was isolated. The deduced amino acid sequence shows 64% identity to
      those of human blue and chicken violet, and less identity (40-49%) to those of
      other vertebrate visual pigment. The mRNA is localized in the miniature short
      single cone cells, which are known to have a sensitivity maximum in the near UV
      region.

PMID- 8736254
TI  - N-acetylaspartylglutamate immunoreactivity in human retina.
AB  - The acidic dipeptide N-acetylaspartylglutamate (NAAG), which satisfies many of
      the criteria for a neurotransmitter, was identified immunohistochemically within
      two human retinae. We observed NAAG immunoreactivity in retinal ganglion cells,
      their dendrites in the inner plexiform layer, and their axons in the optic nerve
      fiber layer. The vast majority of ganglion cells were stained, including
      displaced ganglion cells, ganglion cells of different sizes, and those whose
      dendrites arborized in the inner and outer sublaminae of the inner plexiform
      layer, that is, presumed On- and Off- cells. The sizes of labeled and unlabeled
      cells in the ganglion cell layer, as measured in counterstained material, suggest
      that the unlabeled cells consist primarily or only of displaced amacrine cells.
      We also saw immunoreactivity in small cells along the inner margin of the inner
      nuclear layer, presumably amacrine cells, and in small cells with little
      cytoplasm in the inner plexiform and ganglion cell layers, presumably displaced
      amacrine cells. These results are consistent with a role for NAAG in the
      transmission of visual information from the retina to the rest of the brain.
      Further, they are similar to those reported previously in rat, cat and monkey,
      thus demonstrating the relevance of previous studies to humans.

PMID- 8736255
TI  - Color perception with test and adapting lights perceived in different depth
      planes.
AB  - Adapting to a chromatic light can alter the color appearance of other lights in
      view. The chromatic adapting effect is measured here with the test and adapting
      field perceived in the same depth plane, or perceived in different depth planes
      (using stereo disparity). The measurements show only a weak, though consistent,
      shift in the appearance of the test when adapting field and test are perceived in
      different depth planes, compared to when they are in the same plane. Adding
      complexity to the adapting stimulus, in the form of a second chromatic light
      surrounding the background, alters the appearance of the test but shows no
      dependence on the depth relations. Overall, there is only a small difference in
      chromatic adaptation caused by introducing a three-dimensional representation of
      these stimuli.

PMID- 8736256
TI  - Infant color vision: motion nulls for red/green vs luminance-modulated stimuli in
      infants and adults.
AB  - Four-week-olds, 9-week-olds, and adult subjects were tested with low spatial
      frequency sinusoidal gratings moving at a speed of 25 deg/sec. Luminance
      modulated and red/green gratings were presented either separately, or
      superimposed and moving in opposite directions in a chromatic motion nulling
      paradigm. An adult observer judged the direction of the slow phase of the
      subject's eye movements. Luminance-modulated gratings elicited directionally
      appropriate eye movements in all three age groups, with contrast thresholds
      decreasing markedly with age. For red/green gratings alone, 4-week-olds responded
      only marginally, but 9-week-olds and adults produced consistent directionally
      appropriate eye movements. In the motion nulling condition, 15% contrast
      luminance-modulated gratings were about equally effective in nulling the motion
      of the red/green gratings in all three age groups. A formal model of the motion
      nulling paradigm, separating threshold and equivalent luminance contrast
      parameters, was developed and applied to the data. Model fits showed that
      equivalent luminance contrast was constant or nearly constant across age groups.
      This outcome is consistent with the hypothesis that, with respect to adults,
      infants show a uniform rather than a differential loss of sensitivity to moving
      red/green vs luminance-modulated stimuli.

PMID- 8736257
TI  - Disparity tuning of the stereoscopic (cyclopean) motion aftereffect.
AB  - Across five experiments this study investigated the disparity tuning of the
      stereoscopic motion aftereffect (adaptation from moving retinal disparity).
      Adapting and test stimuli were moving and stationary stereoscopic grating
      patterns, respectively, created from dynamic random-dot stereograms. Observers
      adapted to moving stereoscopic grating patterns presented with a given disparity
      and viewed stationary test patterns presented with the same or differing
      disparity to examine whether the motion aftereffect is disparity contingent.
      Across experiments aftereffect duration was greatest when adapting motion and
      test pattern both were presented with zero disparity and in the plane of
      fixation. Aftereffect declined as disparity of adapting motion and/or test
      pattern increased away from fixation, even under conditions in which depth
      position of adapt and test was equal. This argues against a relative depth
      separation explanation of the decline, and instead suggests that the amount of
      adaptable substrate decreases away from fixation.

PMID- 8736258
TI  - Postsaccadic target blanking prevents saccadic suppression of image displacement.
AB  - Displacement of a visual target during a saccadic eye movement is normally
      detected only at a high threshold, implying that high-quality information about
      target position is not stored in the nervous system across the saccade. We show
      that blanking the target for 50-300 msec after a saccade restores sensitivity to
      the displacement. With blanking, subjects reliably detect displacements as small
      as 0.33 deg across 6 deg eye movements, with correspondingly steep psychophysical
      functions. Performance with blanking in a fixation control is inferior, evidence
      for a saccadic enhancement of sensitivity to image displacement. If blanking is
      delayed so that the target is visible immediately after the saccade in its
      displaced position, performance declines to non-blanking levels. Blanking the
      target before the saccade, and restoring it during the saccade, yields a similar
      but weaker effect. We interpret these results with a model in which the visual
      system searches for the postsaccadic goal target within a restricted
      spatiotemporal window. If it is not found, the assumption of stationarity of the
      world is broken and the system makes use of other information such as
      extraretinal signals for calibrating location.

PMID- 8736259
TI  - A simplified calibration method for three-dimensional eye movement recordings
      using search-coils.
AB  - An algorithm is presented which allows the calibration of three-dimensional eye
      movements in two magnetic fields with two search-coils in one eye, whose relative
      orientation does not have to be known. Prior to recordings a calibration cube is
      placed in front of the eye to measure real and apparent crosstalk, produced by
      imprecisely oriented horizontal or vertical magnetic fields, and to obtain a
      first approximation of offset voltages. For calibration it suffices if one point
      is fixated and, in addition, spontaneous eye movements for 30-60 sec are
      performed. Additional fixation points can be used to improve the calibration.
      Position quaternions are applied for computing eye movement recordings from man
      and monkey and to determine Listing's plane.

PMID- 8736260
TI  - Reduced perceptual dimensionality in extrafoveal vision.
AB  - The classification behaviour of human observers with respect to compound Gabor
      signals is tested at foveal and extrafoveal retinal positions. Classification
      performance is analysed in terms of a probabilistic classification model recently
      proposed by Rentschler, Juttner and Caelli [(1994) Vision Research, 34, 669-687].
      The analysis allows inferences about structure and dimensionality of the
      individual internal representations underlying the classification task and their
      temporal evolution during the learning process. Using this technique it is found
      that the internal representations of direct and eccentric viewing are
      intrinsically incommensurable, in the sense that extrafoveal pattern
      representations are characterized by a lower perceptual dimension in feature
      space relative to the corresponding physical input signals, whereas foveal
      representations are not. The observed deficits cannot be renormalized by size
      scaling (cortical magnification); however, they can be partially reduced by
      learning although the learning progress strongly depends on the observer's
      practice. The structural incommensurability between foveal and extrafoveal
      representations poses constraints on possible forms of foveal-extrafoveal
      interaction, which might have implications on related perceptual phenomena such
      as visual stability across saccadic eye movements.

PMID- 8736261
TI  - Effects on the compensatory responses to positive and negative lenses of
      intermittent lens wear and ciliary nerve section in chicks.
AB  - This study examined the ocular compensation to lens-induced defocus in chick and
      the effect of interrupting lens wear on a daily basis. Eyes fitted with +10 D
      lenses at hatching compensated rapidly, with almost complete compensation after 4
      days of lens wear; they had decreased vitreous chamber depth compared to normal
      eyes and were thus hyperopic when the lenses were removed. In contrast,
      adaptation to the -10 D lenses was much slower, was still incomplete after 9 days
      of lens wear, and in this case, eyes had increased vitreous chamber depth and
      were myopic without the lenses. Adaptation improved when lens wear was delayed
      until 7 days after hatching. The effect of interrupting lens wear by periods of
      normal vision varied with the sign of the lenses worn. Hyperopia was always seen
      in response to +10 D lenses, although the magnitude of the response decreased as
      the duration of lens wear was decreased. In contrast, even brief periods of
      normal vision, i.e., 3 hr, prevented the development of myopia in response to the
      -10 D lenses; this apparent sensitivity to normal vision is similar to that
      reported for form-deprivation myopia. Ciliary nerve section used here to
      eliminate accommodation did not alter these response patterns.

PMID- 8736262
TI  - Effects of a red background on magnocellular functioning in average and
      specifically disabled readers.
AB  - Two experiments were conducted using metacontrast masking to examine responses in
      the magno system of adults, average reading adolescents and adolescents with
      specific reading disability. In Experiment 1 the effects of a red background
      field on the metacontrast functions of adult subjects were investigated. Results
      showed that a red, compared to a photometrically matched white background field,
      significantly attenuated metacontrast magnitude, supporting the interpretation of
      metacontrast as due to magno system suppression of parvo system responses. The
      finding of a red background effect was replicated in Experiment 2 with the two
      adolescent groups. The metacontrast functions of the adolescent groups also
      differed significantly, with those with specific reading disability exhibiting
      weaker metacontrast than the average readers. This result is consistent with a
      deficit in the magno system of individuals with specific reading disability and
      indicates the continuation of the deficit beyond childhood.

PMID- 8736263
TI  - The presence of a magnocellular defect depends on the type of dyslexia.
AB  - Previous studies have identified a magnocellular pathway defect in approximately
      75% of dyslexics. Since these experiments have not classified dyslexia into
      subtypes, the purpose of this experiment was to determine if adult dyseidetic
      dyslexics or dysphoneidetic dyslexics suffer from a defect in the magnocellular
      pathway. Nine dyseidetic dyslexics, eight dysphoneidetic dyslexics, and nine
      normal readers participated in the experiment. Contrast sensitivity functions
      (CSF) were determined with vertically oriented sine wave gratings (0.5, 1.0, 2.0,
      4.0, 8.0, 12.0 c/deg drifting at 1 and 10 Hz) by employing a two-alternative,
      forced-choice technique. The results of the experiment indicated that
      dysphoneidetic dyslexics had reduced sensitivity to low spatial frequencies at 10
      Hz, whereas dyseidetic dyslexics did not have reduced sensitivity at either 1 or
      10 Hz. These results suggest that the type of dyslexia influences whether losses
      in perception are found which are consistent with a magnocellular deficit.

PMID- 8736264
TI  - Colour contrast thresholds in congenital colour defectives.
AB  - The influence of congenital colour defects on a clinical computer test for
      equiluminous colour discrimination is studied. Differences in relative spectral
      sensitivity and changes in colour contrast discrimination are two distinct
      manifestations of the abnormal genes responsible for congenital red-green
      defects. The very simple and rapid method of the heterochromatic flicker
      brightness test acts like an anomaloscope and can be used to distinguish protan
      and deuteran defectives. The depth of the congenital colour defect can be
      quantified by the colour contrast threshold measured in equiluminous conditions
      along a single red-green axis identical for all types of red-green colour
      defectives. Colour contrast thresholds in tritan colour axes are not influenced
      by congenital red-green defects and therefore they are of extreme clinical
      interest to detect and quantify acquired colour defects, even in the presence of
      a previously unknown congenital red-green defect.

PMID- 8736265
TI  - Investigation of phaeochromocytoma.

PMID- 8736266
TI  - Short-term fasting in obesity fails to restore the blunted GH responsiveness to
      GH-releasing hormone alone or combined with arginine.
AB  - OBJECTIVE: Fasting is known to clearly increase both spontaneous and GHRH
      stimulated GH secretion in normal subjects and this effect is likely to be due to
      hypothalamic mechanism(s). Our aim was to clarify the effect of a 3 or 4-day
      fast, on the GH response to GHRH alone or combined with arginine, an amino acid
      probably acting via inhibition of hypothalamic somatostatin release. DESIGN: Two
      tests with GHRH (1 microgram/kg i.v.), administered either alone or in
      combination with arginine (ARG, 0.5 g/kg i.v.) were performed, in a randomized
      order at least 3 days apart. In obese women the two tests were repeated after a 3
      or 4-day fast. PATIENTS: Seven obese women (OB, aged 17-54 years, BMI 42.4 +/-
      3.6 kg/m2, waist-hip ratio (WHR) 0.85 +/- 0.01) and ten healthy women, as control
      subjects (CS, aged 20-44 years, BMI 23.1 +/- 1.1 kg/m2, WHR 0.79 +/- 0.01) were
      studied. MEASUREMENTS: Serum GH and IGF-I levels were measured by
      radioimmunoassay. The GH secretory responses were expressed either as absolute
      values (mU/l) or as areas under the curve (AUC, mU/l/h) calculated by trapezoidal
      integration. IGF-I concentrations were expressed as absolute values (microgram/l)
      with reference to a pure recombinant IGF-I preparation. Results are expressed as
      mean +/- SEM. RESULTS: Basal GH and IGF-I levels in OB were lower than in CS (0.8
      +/- 0.2 vs 4.8 +/- 1.0 mU/l, P < 0.0001 and 120.1 +/- 21.4 vs 188.7 +/- 13.1
      micrograms/l, P < 0.02, respectively). The GHRH-induced GH rise in OB was lower
      (P < 0.00001) than in CS (AUC 340.2 +/- 81.0 vs 2125.0 +/- 199.6 mU/l/h). ARG
      increased the GHRH-induced GH rise in both groups, but in OB the GH response to
      ARG+GHRH (1458.4 +/- 439.0 mU/l/h, P < 0.03 vs GHRH alone) remained lower (P <
      0.0001) than in CS (6396.2 +/- 772.2 mU/l/h, P < 0.01 vs GHRH alone). In spite of
      a reduction in body weight and IGF-I, insulin and glucose levels, in OB fasting
      failed to modify both the basal GH levels and the somatotroph responsiveness to
      GHRH when administered either alone or combined with ARG. An increase in free
      fatty acids (FFA) was also found after fasting. CONCLUSIONS: The results of this
      study demonstrate that in obesity the somatotroph hyporesponsiveness to GHRH,
      either alone or combined with arginine, is not improved by short-term fasting. As
      fasting is considered a CNS mediated stimulus to GH secretion, its
      ineffectiveness in obesity does not support a hypothalamic pathogenesis and
      suggests that long standing metabolic alterations, such as hyperinsulinaemia
      and/or elevated free fatty acids, could play a major role in causing GH
      insufficiency in obese patients.

PMID- 8736267
TI  - Osteopenia as a feature of the androgen insensitivity syndrome.
AB  - OBJECTIVE: The syndrome of androgen insensitivity, a paradigm of a hormone
      resistance syndrome, manifests as failure of masculinization despite normal or
      high concentrations of serum testosterone. The defect in these 46 XY patients
      resides in the androgen receptor gene, with consequent defective androgen action
      and abnormal sexual differentiation. We sought to evaluate whether the adverse
      sequelae of androgen resistance may extend to skeletal tissue by measuring bone
      mineral density in six patients with androgen insensitivity. DESIGN: A cross
      sectional retrospective study. MEASUREMENTS: Bone mineral density was measured by
      means of a Dexa (Hologic QDR 1000 scanner). The diagnosis of androgen
      insensitivity was confirmed in each patient by karyotype and assay of sex
      hormones. RESULTS: The five adult patients with androgen insensitivity had been
      exposed to both defective androgen action and variable periods of oestrogen
      deficiency. The latter resulted from the low circulating oestrogen concentrations
      (for premenopausal females) before gonadectomy and inadequate oestrogen
      replacement after gonadectomy. All five adults with androgen insensitivity had
      osteopenia in both the lumbar spine (T-score -1.52 to -3.85) and femoral neck (T
      score -1.34 to -4.91). CONCLUSIONS: Osteopenia in patients with androgen
      insensitivity may relate to defective androgen action, oestrogen deficiency or a
      combination of the two. These observations have implications for the management
      of patients with androgen insensitivity and may provide insight into the effects
      of androgens on the female as well as the male skeleton.

PMID- 8736268
TI  - Cardiac flow velocity in women with the polycystic ovary syndrome.
AB  - OBJECTIVE: Women with the polycystic ovary syndrome (PCOS) often have several of
      the known risk factors for cardiovascular disease, including hyperinsulinaemia.
      We have therefore investigated variables of cardiac flow in young women with PCOS
      and related them to blood levels of reproductive hormones (LH, FSH, oestradiol
      and testosterone) and also of insulin. DESIGN: A prospective study. PATIENTS:
      Twenty-six young women with PCOS (mean age 22.8 +/- 0.9 years; mean BMI 23.0 +/-
      0.8) and 11 healthy age matched women with regular ovulatory cycles (mean age
      26.3 +/- 1.7 years; mean BMI 22.9 +/- 0.9). MEASUREMENTS: Cardiac flow was
      measured by pulsed wave Doppler echocardiography in the follicular phase of the
      cycle in controls and oligomenorrhoeic women; there was no special timing for
      amenorrhoeic women. The indicators assessed were: ejection fraction (EF), pre
      ejection time (PEP), ejection time (ET), peak systolic flow velocity (PFV),
      acceleration time (AT), flow velocity integral (FVI), mean acceleration (MA),
      diastolic time (DT), early diastolic filling time (Ei), atrial filling time
      interval (Ai), peak velocity of the early diastolic filling (PE) and peak
      velocity of the atrial filling (PA). Serum LH, FSH, oestradiol, testosterone,
      SHBG and insulin concentrations were analysed by standard RIA. RESULTS:
      Significantly lower PFV (1.055 +/- 0.025 vs 1.242 +/- 0.054, P = 0.0006) and MA
      (17.06 +/- 0.57 vs 23.00 +/- 1.49, P = 0.0001) and longer AT (0.063 +/- 0.001 vs
      0.056 +/- 0.004, P = 0.026) were found in women with PCOS as compared to age
      matched controls. Significant negative correlation between serum fasting insulin
      concentration and EF (r = -0.725, P = 0.002), PFV (r = -0.719, P = 0.0025), FVI
      (r = -0.654, P = 0.008) and MA (r = -0.757, P = 0.001) was observed in the 15
      women with PCOS in whom insulin was measured. CONCLUSION: An inverse relation
      between serum fasting insulin level and left ventricular systolic outflow
      parameters suggests that insulin is associated with the decreased systolic flow
      velocity observed in women with PCOS.

PMID- 8736269
TI  - Prevalence of Helicobacter pylori in acromegalic patients during treatment with
      octreotide.
AB  - BACKGROUND: Octreotide, a synthetic long-acting analogue of somatostatin, now has
      an established role in the treatment of acromegaly. In acromegalic patients
      treated with octreotide there is an increased incidence of gallstones and
      possibly gastritis. OBJECTIVES: (1) To compare the seroprevalence of Helicobacter
      pylori (H. pylori) infection, in acromegalic patients treated with octreotide to
      that in patients given other treatment modalities. (2) To study retrospectively
      the temporal relation between H. pylori acquisition and octreotide treatment.
      PATIENTS: Three groups of acromegalic patients were studied; 35 (20 M) had been
      treated with octreotide, 17 (10 M) with bromocriptine and 19 (12 M) had received
      no pharmacological intervention (untreated, surgically treated or treated with
      radiotherapy). DESIGN/MEASUREMENTS: The presence of H. pylori infection was
      assessed serologically (Bio-Rad GAP test for IgG), using stored serum, on the
      most recent sample from each patient and on serial samples from patients treated
      with octreotide. RESULTS: The prevalence of H. pylori seropositivity was similar
      in each treatment group, 34, 35 and 37%, respectively. Mean age and duration of
      acromegaly were similar in the first two groups. Patients who had never received
      medical treatment were slightly younger. GH levels were similar in all three
      groups. Patients on octreotide who were seropositive for H. pylori did not differ
      from those with negative serology with respect to age, duration of acromegaly,
      duration of octreotide treatment or serum GH level. Serial samples in octreotide
      treated patients showed a change in status in only one patient; 18 patients
      continued with negative serology during a mean period of 30 (range 4-62) months.
      In each of the 6 patients with persistently positive serology during octreotide
      treatment, stored samples predating octreotide therapy were shown to have already
      been positive. CONCLUSIONS: The seroprevalence of H. pylori infection in
      acromegalic patients does not appear to be increased in a manner dependent on the
      type or duration of medical treatment. In particular, octreotide therapy, while
      causing the development of histological gastritis in some patients, does not
      appear to induce the development of H. pylori infection.

PMID- 8736271
TI  - High incidence of juvenile Graves' disease in Hong Kong.
AB  - OBJECTIVE: Childhood Graves' disease has been reported to be rare and
      epidemiological data on its incidence are limited. In our Paediatric Endocrine
      Clinic, Graves' disease was the most common thyroid disorder seen. There is no
      previous epidemiological study on Graves' disease in Chinese children. This study
      was performed to determine the incidence of childhood Graves' disease in Hong
      Kong Chinese. DESIGN AND PATIENTS: We established a registry of childhood Graves'
      disease in 1990 at our centre, which has a catchment population of 1,010,000 with
      240,000 under 15 years of age. Graves' disease was diagnosed on clinical
      features, diffuse thyroid gland enlargement, elevated free thyroxine or
      triiodothyronine levels with suppressed TSH level. All confirmed cases were
      recorded prospectively. Population data were obtained from the Statistics
      Department of the Hong Kong Government. RESULTS: Forty-six Chinese children under
      15 years of age had a confirmed diagnosis of Graves' disease during the study
      period from January 1990 to December 1994. The overall incidence was
      3.8/100,000/year with a 95% confidence interval of 1.8-7.3/100,000/year.
      Incidence was low in children under 4 years. The highest incidence was in girls
      between 10 and 14 years of age at 15.5/100,000/year. The cumulative incidence for
      boys and girls of developing Graves' disease during the first 15 years was 11 and
      104 per 100,000 respectively. CONCLUSIONS: Our data demonstrate a very high
      incidence of Graves' disease in Hong Kong Chinese children, with an overall
      incidence about 5 times that reported in Danish children. A female predominance
      was found in all three age groups (0-4, 5-9 and 10-14 years) and was particularly
      striking in the adolescent girls.

PMID- 8736270
TI  - Whole body and regional soft tissue changes in growth hormone deficient adults
      after one year of growth hormone treatment: a double-blind, randomized, placebo
      controlled study.
AB  - OBJECTIVE: Adults with GH deficiency (GHD) exhibit changes in body composition.
      Studies of the effects of GH substitution on body composition have been short
      term or not adequately controlled. The purpose of this study was to evaluate the
      long-term effects of GH on soft tissue using dual-energy X-ray absorptiometry
      (DEXA). This technique enables assessment of whole body as well as regional soft
      tissue composition. DESIGN: A double-blind, randomized, placebo-controlled study
      in patients with acquired GHD. The therapeutic regime consisted of biosynthetic
      human GH (2.0 IU/m2 per day) or placebo, given as a daily subcutaneous injection
      at 2000 h for 12 months. PATIENTS: Twenty-nine patients with acquired GHD (GH <
      10 micrograms/l (< 20 mU/l) following standard provocative tests) in whom
      additional hormone replacement was maintained. MEASUREMENTS: Soft tissue
      determinations by DEXA scan, height, weight, foot volume and finger circumference
      were recorded together with serum IGF-I at baseline and after 12 months. RESULTS:
      Twelve months of GH therapy induced a total fat mass (FM) reduction of (mean +/-
      SEM) 4.88 +/- 0.58 kg (P < 0.002) (n = 13) corresponding to 21.5% of the total
      FM. The reduction in fat was most marked in the trunk, i.e. 3.07 +/- 0.29 kg (P <
      0.002) corresponding to 61% of the total FM reduction. Total lean soft tissue
      mass (LSTM) increased by 3.31 +/- 0.81 kg (P < 0.001). Regional changes for arm
      and leg in the GH group amounted to 0.32 +/- 0.08 kg (P < 0.002) and 0.71 +/-
      0.14 kg (P < 0.002), respectively, without accompanying significant changes in
      truncal LSTM between the groups. The foot volume was increased by 55.8 +/- 15.7
      ml (P < 0.007) and the finger circumference by 2.67 +/- 0.5 mm (P < 0.005) on
      active treatment with no significant changes in the placebo group. CONCLUSIONS:
      Twelve months of GH therapy induced marked changes in soft tissue; fat mass was
      reduced, particularly in the trunk (61% of total fat mass reduction) whereas lean
      soft tissue mass increased more in the extremities. The data imply that GH
      induced changes in body composition are maintained with long-term therapy.

PMID- 8736272
TI  - Thyroid cancer and thyroiditis in the goitrous region of Salta, Argentina, before
      and after iodine prophylaxis.
AB  - OBJECTIVE: The importance of iodine intake and thyroiditis in the pathogenesis of
      thyroid cancer remains controversial. We have investigated the natural history of
      thyroid cancer and thyroiditis in a goitrous region before and after iodine
      prophylaxis over a 31-year period. DESIGN: For the analysis of thyroid cancer the
      material was divided in two periods. The first 15 years (59 cases), including 5
      years before prophylaxis, was compared with the second 16 years (85 cases), a
      period well after iodine supplementation of salt. Histological diagnosis of the
      tumours was based on the WHO system. Moderate to severe thyroiditis in the non
      tumoral surrounding thyroid from female patients was recorded. For this, the
      material was analysed in the two periods in relation to the introduction of
      iodine prophylaxis in 1963, taking account of the age of the patients. RESULTS:
      Papillary carcinomas formed the largest group of tumours in both periods, with
      nearly twice as many in the second period as the first, while the numbers of
      follicular and medullary carcinomas remained about the same. The ratio of
      papillary to follicular carcinoma rose from 1.7:1 in the first period to 3.1:1 in
      the second. All three thyroid lymphomas were of the non-Hodgkin's type, and all
      occurred in the second period in females aged over 50. A severe lymphoid
      thyroiditis was present in the two cases with assessable background thyroid
      tissue. The frequency of lymphoid infiltrate in females rose from 8% (1/12)
      before 1963 to 25% (18/72) after prophylaxis in the whole series. After salt
      prophylaxis, thyroiditis was more frequent in patients with papillary carcinoma
      in general (31%), and clinically significant papillary carcinomas in particular
      (35%), than in those with non-papillary tumours (6%) (chi 2, P < 0.05 and P <
      0.025, respectively). CONCLUSIONS: Our observations indicate that a high dietary
      intake of iodine may be associated with a high frequency of papillary carcinoma
      and thyroiditis, and that thyroiditis is more commonly associated with papillary
      carcinoma than with other thyroid tumours. The occurrence of non-Hodgkin's
      lymphomas only in the post-prophylaxis period may be linked to an increase in
      thyroiditis.

PMID- 8736273
TI  - Melatonin and the pituitary-thyroid axis status in blind adults: a possible
      resetting after puberty.
AB  - OBJECTIVE: Increased levels of free thyroid hormones have been previously
      described in prepubertal blind subjects and have been thought to be a consequence
      of a partial target organ refractoriness due to the early and prolonged lack of
      light perception. The aim of this study was to clarify whether this abnormality
      is permanent or transient and the interrelationships between melatonin and
      thyroid hormone secretion. MEASUREMENTS: Total and free thyroid hormones, TSH,
      thyroxine-binding globulin (TBG), reverse triiodothyronine (rT3) and melatonin
      were measured in plasma samples obtained at 0800 h (two hours after lights-on) in
      a group of 11 totally (group 1) and 16 partially (group 2) blind adult patients
      and in 10 age-matched healthy subjects. RESULTS: Both totally and partially blind
      patients showed melatonin levels higher than in controls (330 +/- 106 pmol/l,
      group 1 and 361 +/- 159 pmol/l, group 2, respectively; controls: 53 +/- 12
      pmol/l, P < 0.001 vs both groups), but fT4, fT3, T4, T3 TSH, rT3 and TBG
      concentrations showed no significant differences from controls. CONCLUSIONS: A
      possible resetting of pituitary-thyroid axis regulation can occur in blindness
      after puberty; variations of melatonin secretion could play a role in this. The
      inhibitory effect of melatonin on thyroid gland function found in animals does
      not seem to occur in humans. Elevated melatonin levels, both in patients with
      total blindness and in those with light perception only, suggest that more
      complex mechanisms other than light signalling are involved in the changes of
      melatonin secretion in blindness.

PMID- 8736274
TI  - Neuroendocrine evidence for an association between hypothyroidism, reduced
      central 5-HT activity and depression.
AB  - OBJECTIVE: The incidence of depression in those with hypothyroidism is increased
      compared to healthy populations, though the mechanism for this is unclear. We
      tested the hypothesis that central 5-HT activity is reduced in hypothyroidism,
      and that this subsequently lowers the threshold for developing depression.
      PATIENTS: Twenty subjects entered the study: 10 drug free hypothyroid patients
      and 10 age, sex, weight and menstrual cycle matched controls. MEASUREMENTS:
      Patients were diagnosed as being depressed using DSM-IIIR criteria and rated
      using the Hamilton Rating Scale for Depression (HAM-D) and Beck Depression
      Inventory (BDI). Cortisol and prolactin responses to dexfenfluramine, a centrally
      acting 5-HT releasing agent, were used as an index of central 5-HT responsivity.
      RESULTS: Both cortisol and PRL responses were reduced in the hypothyroid group
      relative to the controls. Peak cortisol responses were inversely correlated to
      TSH levels. Four of the 10 patients were clinically depressed. Depressed patients
      had higher TSH levels than their non-depressed counterparts, and TSH levels were
      positively correlated with HAM-D and BDI scores. CONCLUSIONS: These findings
      support animal work suggesting that hypothyroidism reduces central 5-HT activity.
      They also suggest a threshold effect in that higher TSH levels predicted both
      lower 5-HT mediated endocrine responses and the presence of clinical depression.

PMID- 8736275
TI  - Peripheral glucose metabolism in human hyperprolactinaemia.
AB  - OBJECTIVE: Prolactin has important biological actions in several species which
      include metabolic control and water/electrolyte balance. However, human PRL has
      generally been characterized as a mammotrophic hormone and it is unknown whether
      PRL has any important metabolic actions. This study was thus conducted to
      evaluate the effect of hyperprolactinaemia on peripheral muscle glucose
      metabolism. DESIGN: The study was designed to determine forearm muscle glucose
      uptake and utilization (oxidative and non-oxidative metabolism) in normal and
      hyperprolactinaemic subjects in the post-absorptive state and for 3 hours after
      the ingestion of 75 g of glucose. Peripheral glucose metabolism was analysed by
      the forearm technique to estimate muscle exchange of substrates combined with
      local indirect calorimetry. PATIENTS: Eight hyperprolactinaemic patients (HP
      group, 6 females and 2 males) and ten normal subjects (N group, 7 females and 3
      males) were studied. The hyperprolactinaemic patients showed no clinical or
      laboratory evidence of acromegaly or hypothyroidism and were not using any PRL
      releasing drugs. MEASUREMENTS: Forearm blood flow was measured by capacitance
      plethysmography and arterial and venous blood samples were drawn simultaneously
      to determine plasma glucose, serum FFA, total blood CO2 and O2 and serum insulin
      in the post-absorptive state (0 time) and at 30, 60, 120 and 180 minutes after
      glucose ingestion. RESULTS: No significant difference in glucose uptake by the
      forearm muscle tissue was observed between the N and HP groups (823 +/- 103 vs
      828 +/- 110 mumol/100 ml forearm 3 h, respectively), nor were any significant
      differences observed in the intracellular utilization of glucose (oxidative and
      non-oxidative metabolism). However, the serum insulin levels after glucose
      ingestion were significantly higher in hyperprolactinaemic patients than in
      normal subjects, especially at 30 (N 283 +/- 46 vs HP 581 +/- 133 pmol/l) and 60
      minutes (N 291 +/- 37 vs HP 544 +/- 61 pmol/l). Furthermore, after glucose
      ingestion the suppression of serum FFA levels was smaller in the
      hyperprolactinaemic patients than in normal subjects. CONCLUSIONS: This study
      demonstrated that insulin resistance is associated with the presence of
      spontaneous human hyperprolactinaemia. The hyperinsulinaemia detected in the
      hyperprolactinaemic patients after the oral glucose stimulus did not determine a
      proportional increase in forearm glucose uptake and utilization, which were
      similar to the normal levels. The suppression of serum free fatty acid
      concentrations was also smaller in hyperprolactinaemic patients during the oral
      glucose challenge, suggesting an impaired antilipolytic effect of insulin.

PMID- 8736276
TI  - Serum testosterone and its relation to bone mineral density and body composition
      in normal males.
AB  - OBJECTIVE: Bone mineral density (BMD) declines with age in both men and women,
      predisposing the elderly to osteoporosis and fractures. Although there are
      extensive data about post-menopausal osteoporosis, there is relatively little
      information concerning the decrease in BMD with age in normal men, particularly
      the contribution of declining gonadal function with age to BMD. In the present
      study, we investigated the effect of age on the pituitary-gonadal axis in normal
      males and its relation to BMD and body composition. SUBJECTS: Ninety healthy Thai
      males in the Bangkok Metropolitan area without a history of smoking or
      significant alcohol consumption were studied. MEASUREMENTS: Serum testosterone
      (T), free testosterone (FT), LH and FSH were measured by radioimmunoassay in
      fasting blood samples obtained in the morning between 0600 and 1000 h. BMD at
      anteroposterior L2-L4, lateral L2-L4, femoral neck, femoral trochanter and Ward's
      triangle were determined by dual-energy X-ray absorptiometry. RESULTS: There were
      significant declines with age in BMD at lateral L2-L4 (r = -0.37, P < 0.001),
      femoral neck (r = -0.49, P < 0.0001), Ward's triangle (r = -0.54, P < 0.0001) but
      not at anteroposterior L2-L4 or femoral trochanter. Serum FT (r = -0.56, P <
      0.0001) but not T (r = -0.19, P = 0.07) decreased with age. Serum LH (r = 0.27, P
      < 0.001) and FSH (r = 0.4, P < 0.0001) increased with age suggesting a defect in
      gonadal androgen synthesis or possibly a secretion of bioinactive LH. Serum FT
      concentrations were significantly correlated to lateral L2-L4 (r = 0.27, P <
      0.05), femoral neck (r = 0.48, P < 0.0001) and Ward's triangle (r = 0.50, P <
      0.0001) BMD. After controlling for age, declining FT with age was still
      associated with a decrease in BMD in femoral neck (P < 0.05) and Ward's triangle
      (P < 0.05) but not in lateral L2-L4. The proportion of body fat increased with
      age (r = 0.3, P < 0.01). Decreased serum T, but not FT, was associated with
      increased body fat after age was taken into account (P < 0.0001). CONCLUSIONS:
      There is a decline in serum free testosterone together with increases in LH and
      FSH with age in healthy males. The decrease in serum free testosterone is
      partially associated with the age-related decline in bone mineral density added
      to the effect of age at the femoral neck and Ward's triangle. Testosterone but
      not free testosterone is associated with age-related increase in body fat.

PMID- 8736277
TI  - Spontaneous follicular and luteal function in infertile women with
      oligomenorrhoea: role of luteinizing hormone.
AB  - OBJECTIVE: There is a paucity of longitudinal endocrine studies of infertile
      patients with oligomenorrhoea. We have assessed the frequency and quality of
      spontaneous follicular development and luteal function in patients with
      oligomenorrhoea and infertility (PCOS), and have related the observed criteria to
      circulating LH activity. DESIGN: Prospective detailed investigations in a cohort
      of unselected patients. PATIENTS: Infertile women with oligomenorrhoea (PCOS, n =
      131) presenting to the infertility clinic at the Royal Infirmary, Glasgow.
      MEASUREMENTS: Patients were monitored with frequent plasma oestradiol (E2)
      concentration assessments over a minimum period of 3 weeks, starting more than 2
      weeks after a menstrual bleed. When follicular maturation was identified the
      patient provided daily blood samples through to her ensuing menstrual bleed, and
      E2, progesterone, total testosterone, FSH and LH were assessed in these samples.
      Luteal phase progesterone profiles were assessed between the days LH surge +2 and
      LH surge +6 by means of a progesterone index. RESULTS: Forty-eight per cent of
      the patients showed evidence of follicular development. The oestradiol profiles
      in the patients showing follicular growth were normal, but the progesterone curve
      was sub-normal in the early luteal phase, due to a high proportion of deficient
      luteal phases. The mean LH concentrations were elevated in the whole group, but
      no difference was observed between the mean LH values for those patients showing
      spontaneous follicular development and those who did not, and the incidence of
      ovulation was similar in the normal LH and elevated LH groups. Similarly, no
      relation was established between LH and the quantitative assessment of luteal
      phase progesterone profiles (progesterone index), and the distribution of
      progesterone indices was similar in the normal LH and elevated LH groups.
      Testosterone concentrations were positively correlated with LH (p = 0.008) but
      not with the incidence of spontaneous follicular growth. There was no significant
      difference in the incidence of spontaneous ovulation between the patients with
      elevated or normal mean follicular phase testosterone concentrations. CONCLUSION:
      The data indicate that both LH and testosterone secretion in PCOS were closely
      linked, but that neither was directly linked to the incidence or inhibition of
      spontaneous follicular development in PCOS, or to the disturbance in luteal phase
      progesterone profiles.

PMID- 8736278
TI  - Osteoporosis in Turner's syndrome and other forms of primary amenorrhoea.
AB  - OBJECTIVE: Osteopenia in Turner's syndrome is well recognized. This study is
      aimed to elucidate whether this is an intrinsic feature of the disorder, or is a
      non-specific feature resulting from oestrogen deficiency. DESIGN: Comparison of
      bone mineral density and fracture rate in Turner's patients and in 46,XX women
      with equivalent oestrogen deprivation from other causes. SUBJECTS: One hundred
      and twenty women in the reproductive age range (16-45 years): 40 with Turner's
      syndrome, 40 with other forms of primary amenorrhoea, and 40 healthy controls
      matched to patients for duration of oestrogen usage. MEASUREMENTS: Measurement of
      bone mineral density in the lumbar spine (and femoral neck in some subjects) by
      dual-energy X-ray absorptiometry, and reported history of fracture. RESULTS:
      Vertebral bone mineral density was similar in women with Turner's syndrome (mean
      0.84, SD 0.11 g/cm2) and those with other causes of primary amenorrhoea (mean
      0.81, SD 0.11 g/cm2; P = 0.26). Both groups had severe osteopenia compared with
      healthy controls (mean 1.06, SD 0.09 g/cm2, P < 0.0005, confirmed after
      correction for height and weight). Fractures had been sustained by 45% (10/22) of
      Turner's patients for whom information was available, a high frequency compared
      with controls (P = 0.014); half of these were at 'osteoporotic' sites of fracture
      (wrist, vertebra, femoral neck). CONCLUSION: Osteopenia in Turner's syndrome is
      not an intrinsic feature specific to this disorder, but results from extreme
      oestrogen deprivation. Early treatment with oestrogen is therefore recommended.

PMID- 8736280
TI  - Autonomous nodular hyperplasia of the adrenal cortex: tertiary hypercortisolism?
AB  - Two cases of Cushing's syndrome are reported in which apparently autonomous
      adrenal adenomata were associated with the presence of pituitary tumours. In one
      case the patient was apparently cured by unilateral adrenalectomy, although she
      was noted to have radiological evidence of an intrasellar tumour; serum cortisol
      was not suppressed by dexamethasone and ACTH was undetectable. Serum ACTH in the
      second case was initially 31 ng/l but became undetectable during the course of
      investigation. Transsphenoidal removal of a corticotroph adenoma did not affect
      serum cortisol and she proceeded to unilateral adrenalectomy. The pathogenesis of
      autonomous macronodular hyperplasia is discussed, as well as the options for
      management.

PMID- 8736279
TI  - Cardiovascular and metabolic responses to adrenaline infusion in patients with
      short-term hypothyroidism.
AB  - OBJECTIVE: The relation between the clinical manifestations of thyroid disease
      (both hypo and hyper-thyroidism) and tissue sensitivity to catecholamines remains
      uncertain. It has been suggested that tissue adrenergic responsiveness is
      decreased in hypothyroidism, but the reports have been conflicting and have
      invariably focused on a single physiological response. Therefore the aim of the
      present study was to determine in patients with moderate, short-term, symptomatic
      hypothyroidism the responses of heart rate, systolic and diastolic blood
      pressure, forearm blood flow and metabolic rate to adrenaline infused at a rate
      known to achieve plasma concentrations in the middle of the physiological range.
      PATIENTS: Ten subjects (5M, age 43 +/- 3 years, mean +/- SEM) were studied. All
      were on thyroxine replacement for hypothyroidism following either thyroidectomy
      or radioactive iodine and had been biochemically euthyroid for at least 6 months.
      DESIGN: Studies were performed in random order. One study was undertaken on full
      replacement therapy and the other after 50 micrograms thyroxine daily for 2
      weeks. After basal, supine measurements adrenaline was infused at 25 ng/kg/min
      for 30 minutes. MEASUREMENTS: Heart rate, blood pressure, blood glucose,
      metabolic rate and forearm blood flow were measured at rest and at 10-minute
      intervals throughout the adrenaline infusion. RESULTS: Free T4 (10.6 +/- 1.3 vs
      17.6 +/- 2.0 pmol/l, P < 0.001) and free T3 (3.6 +/- 0.2 vs 4.6 +/- 0.3 pmol/l, P
      < 0.01) concentrations were significantly lower on 50 micrograms thyroxine than
      full replacement therapy. Fasting blood glucose concentrations (4.7 +/- 0.2 vs
      4.7 +/- 0.1 mmol/l) were similar. The resting adrenaline concentrations were
      comparable, 0.29 +/- 0.18 and 0.24 +/- 0.14 nmol/l on 50 micrograms thyroxine and
      full replacement therapy respectively, and increased to a similar level (2.36 +/-
      0.39 and 2.36 +/- 0.35 nmol/l) throughout the adrenaline infusion. The resting
      heart rate and metabolic rate were significantly lower on 50 micrograms thyroxine
      than full replacement therapy (68 +/- 2 vs 72 +/- 3 beats/min, P < 0.01; and 4.48
      +/- 0.35 vs 4.88 +/- 0.39 kJ/min, P < 0.01) respectively, but the increase in
      heart rate (7 +/- 2 vs 8 +/- 2 beats/min) and metabolic rate (0.43 +/- 0.09 vs
      0.43 +/- 0.06 kJ/min) did not differ on the two study days. Resting systolic
      blood pressure, diastolic blood pressure and forearm blood flow were comparable
      on 50 micrograms thyroxine and full replacement therapy as were the changes in
      systolic blood pressure (1 +/- 1 vs 1 +/- 1 mmHg), diastolic blood pressure (-7
      +/- 2 vs -7 +/- 1 mmHg), forearm blood flow (1.4 +/- 0.1 vs 1.7 +/- 0.2
      ml/min/100ml forearm) and blood glucose concentration (0.7 +/- 0.1 vs 0.7 +/- 0.1
      mmol/l). CONCLUSIONS: Patients with short-term hypothyroidism appear to have a
      normal response to adrenaline infusion despite reduced baseline heart rate and
      metabolic rate. Thus, under physiological and mild pathophysiological conditions
      there appears to be no evidence of any synergy between thyroid status and
      sensitivity to catecholamines.

PMID- 8736281
TI  - No mutation at codon 918 of the RET gene in a family with multiple endocrine
      neoplasia type 2B.
AB  - Multiple endocrine neoplasia type 2B (MEN 2B) is a rare cancer syndrome which is
      inherited in an autosomal dominant manner. The molecular basis of this condition
      has recently been defined as a mutation of codon 918 of exon 16 of the RET proto
      oncogene. The mutation in codon 918 has been described in 69 out of 72 families
      with MEN 2B. We have studied a brother and sister who undoubtedly have the
      features of MEN 2B as evidenced by medullary thyroid carcinoma,
      phaeochromocytoma, mucosal neuromas and skeletal abnormalities. Neither of these
      patients has the classic gene mutation at codon 918 of exon 16 of the RET proto
      oncogene, and although exons 2-20 have also been sequenced, no abnormality has
      been found. DNA analysis is a sensitive method of screening families for the MEN
      2 syndromes. The absence of the mutation at codon 918 in a phenotypically normal
      individual would refute the diagnosis of MEN 2B, but in an individual with some
      of the features of MEN 2B would make the clinician reconsider the diagnosis. This
      family demonstrates that, although it is rare, the absence of the mutation in
      codon 918 of exon 16 of the RET proto-oncogene does not always exclude the
      diagnosis of MEN 2B. In such families routine biochemical screening for medullary
      thyroid carcinoma and phaeochromocytoma must be maintained for all individuals at
      genetic risk.

PMID- 8736283
TI  - Lymphocytic hypophysitis.

PMID- 8736282
TI  - Successful localization of an occult ACTH-secreting bronchial carcinoid tumour
      with 111indium-DTPA labelled octreotide.
AB  - Ectopic ACTH secretion due to occult carcinoid tumours is an occasional cause of
      ACTH dependent Cushing's syndrome. In many cases the ectopic source may be
      obvious, but sometimes no obvious source is evident, the so-called occult ectopic
      syndrome. Due to their small size, localization of such occult tumours,
      particularly bronchial carcinoids, may be extremely difficult. Whole body CT and
      venous sampling studies have been used but are not always successful in
      determining the site of such lesions. We report a 40-year-old patient with the
      ectopic ACTH syndrome due to a 0.6-cm bronchial carcinoid tumour which was
      successfully localized by 111indium-DTPA labelled octreotide scintigraphy.

PMID- 8736284
TI  - Hypercalcaemia and secondary hypoadrenalism due to Sheehan's syndrome.

PMID- 8736285
TI  - MRI diagnosis of partial tears of the anterior cruciate ligament.
AB  - In an attempt to define the magnetic resonance imaging (MRI) features of partial
      tears of the anterior cruciate ligament (ACL) we retrospectively analysed the MRI
      scans of 30 patients with a recent arthroscopic finding of a normal, a partial or
      a completely torn ACL. On review of the original reports MRI correctly predicted
      9/9 (100 per cent) complete ACL tears, 11/12 (92 per cent) normal ACLs but only
      1/9 (11 per cent) partial ACL tears. On analysis of the MRI there were four
      features which helped to differentiate partial ACL tears from either complete ACL
      tears or normal ligaments. These were the appearance of some intact fibres,
      thinning of the ligament, a wavy or curved ligament and the presence of an
      inhomogeneous mass posterolateral to the ACL. We propose that these findings may
      be indicators of partial ACL tear.

PMID- 8736286
TI  - Finger injuries from infant mittens; a continuing but preventable hazard.
AB  - During the last 4 years, three infants have presented with finger-tip injuries
      secondary to entrapment in woollen/synthetic mittens. The accident happened at
      home in one case but the other two occurred in different neonatal units.
      Spontaneous amputation of the terminal phalanx of the index finger occurred in
      two patients but in the other there was complete healing. This problem may be
      avoided by restricting the use of mittens, by changing their design, and by a
      greater awareness of this hazard.

PMID- 8736287
TI  - Admission after head injury: how many occur and how many are recorded?
AB  - This study attempted to determine how many patients admitted with a head injury
      do not have the diagnosis recorded in the medical notes, and the factors
      associated with this failure. This observational study took place over four weeks
      with a review of notes of all patients in the trauma service admission wards in a
      District and Teaching hospital. All patients aged 16 years to 65 years admitted
      to the inpatient trauma wards were included, and the frequency of diagnosis of
      head injury made by the investigator was compared with the frequency of a
      recorded diagnosis of head injury in the notes. Of 107 patients admitted 47 had
      had a head injury; 24 did not have the diagnosis recorded, and four of these had
      moderate or severe injuries. A failure to record diagnosis was more likely in the
      presence of other more severe injuries (21/28), and in patients with minor or
      trivial injuries (20/30). We conclude that head injury registers are likely to
      miss a significant number of patients admitted to hospital unless specific
      attempts are made to identify and record the diagnosis.

PMID- 8736288
TI  - Evaluating performance of the Revised Trauma score as a triage instrument in the
      prehospital setting.
AB  - In this study, we have evaluated the performance of the Revised Trauma Score
      (RTS) as a triage instrument in the prehospital setting in The Netherlands. To
      this end we analysed prehospital and clinical data on 398 injured patients in an
      urban-rural area in the east of the Netherlands. Our study included injured
      patients aged over 15 who were alive at the time the ambulance arrived. We found
      a comparatively low prevalence of major injuries in the prehospital setting,
      which varied with the definition used (for patients with an HTI-ISS > or = 18, it
      was 5.8 per cent, for HTI-ISS > or = 20 it was 3.7 per cent; for a modified HTI
      ISS criterion it was 5.3 per cent and 2.7 per cent needed major emergency
      therapy). Estimates of sensitivity were also rather low and varied with the
      definition used (38 per cent for HTI-ISS > or = 18; 56 per cent for HTI-ISS > or
      = 20, 45 per cent for the modified HTI-ISS criterion and 76 per cent for major
      emergency treatment). The specificity and the predictive value of a lowered RTS,
      however, were 94 per cent and 26 per cent respectively for all definitions used.
      The conclusion of this study is that the performance of the RTS in this study
      population is poorer than expected from earlier studies. The low prevalence of
      major injuries in the prehospital setting in The Netherlands and the distribution
      of case severity may possibly explain these results.

PMID- 8736289
TI  - Rogers' posterior cervical fusion--a 3-month radiological review.
AB  - Rogers described his technique of spinal fusion in 1942, and since then numerous
      other techniques have been described but no large series describing the
      anatomical results has been reported. To assess the technical success of Rogers'
      technique, to identify factors that contribute to less than ideal anatomical
      results, and to suggest methods of avoiding potential pitfalls, the anatomical
      results of Rogers' posterior cervical fusion were compared with what we consider
      an ideal anatomical result by analysis of the 12-week post-operative
      flexion/extension radiographs. One hundred and sixty-one Rogers-type posterior
      cervical fusions using either wire or Ethibond were performed for flexion
      injuries. The 12-week post-operative flexion extension radiographs were assessed
      for union, fusion of extra levels, residual kyphosis/listhesis, excessive
      lordosis, and hypermobility. Results were related to the presence of associated
      fractures, using the chi 2 test. Bony union was seen in 100 per cent of cases.
      Fusion of additional levels occurred in 40 (25 per cent), residual kyphosis in 54
      (34 per cent), listhesis in 14 (9 per cent), and excessive lordosis in seven (4
      per cent). Hypermobility at the adjacent level occurred in 10 (6 per cent), and
      at a distant level in five (3 per cent). Statistically significant associations
      occurred between fusion of extra levels and fractures, residual kyphosis and
      fractures, excessive lordosis with the use of wire rather than Ethibond, and the
      desired anatomical result with absence of fracture. The Rogers technique is a
      safe, easy and reliable method of achieving cervical fusion, with a 100 per cent
      fusion rate at 3 months in this series. However, the intended position of fusion,
      between 1 degree-5 degrees of lordosis, with normal alignment, is not always
      achieved. There is also a high incidence of fusion of levels other than those
      intended. We believe that the incidence of these problems could be reduced by
      more attention to surgical detail.

PMID- 8736290
TI  - Arthroscopy of the knee in war injuries.
AB  - The results of arthroscopic removal of bullets and explosive ordnance fragments
      from the knee joint are presented. The operations were performed on 18 patients
      injured in battle operations in the former Yugoslavian territory in the period
      September 1991-October 1994. The indications for arthroscopic operations were
      positive radiographic findings, a locked knee, pain, effusion, instability and
      painful movement. In 13 patients, bullets and explosive ordnance fragments were
      removed arthroscopically, while in five patients, the clinic findings were found
      to be misleading. There were no complications from the arthroscopic surgery.

PMID- 8736291
TI  - Arthroscopic retrieval of metal foreign bodies from the knee joint after war
      wounds.
AB  - From 1991 to 1995 metal bodies were removed from 16 knee joints (in 16 patients)
      using arthroscopic procedures. In 14 patients the wound resulted from explosive
      devices and in two from rifle bullets. Nine patients had more than one wound.
      Arthroscopy was performed on average 8.23 months after the injury took place
      (ranging from 14 days to 4 years). One metal foreign body was retrieved from 13
      patients, two from two and four from one patient. The size of the metal foreign
      bodies varied from 2 to 24 mm, with an average of 8.61 mm. Different degrees of
      joint damage were present in all but one patient. The metal bodies were found in
      the posterolateral angle by the popliteus tendon in four patients, in three of
      whom the metal bodies went into this position during arthroscopy.

PMID- 8736292
TI  - Fixation of intracapsular femoral neck fractures with a one-hole plate dynamic
      hip screw.
AB  - The results of internal fixation of 55 subcapital fractures of the femoral neck
      with a one-hole plate dynamic hip screw are presented. Two fractures could not be
      satisfactorily fixed and the procedures were converted to hemi-arthroplasties,
      but the remainder united within 6 months. The rate of avascular necrosis after
      union was 3 per cent in undisplaced and 31 per cent in displaced fractures. This
      method of fixation appears to produce a lower non-union rate than multiple pins
      in suitable fractures without affecting the incidence of late avascular necrosis.

PMID- 8736293
TI  - Injury reduction by the airbag in accidents.
AB  - Today an increasing number of automobiles are being equipped with additional
      passive safety devices: driver and passenger airbags. To examine the efficiency
      of the airbag in real road traffic accidents, a collective study was conducted
      from 181 traumatology centres throughout Germany. The inquiry was answered by 81
      per cent of the medical centres contacted. From the evaluation of 122 accident
      victims in 1993 who were protected with an airbag the following was concluded.
      The patients treated in surgical and in traumatological departments suffered
      predominantly superficial injuries of the head, cervical vertebra and thorax.
      Some of these chiefly superficial wounds, such as abrasions and bruises, were
      initiated by contact with the airbag. It is remarkable that 72.1 per cent of the
      airbag-protected patients suffered a maximum of MAIS 2. What is also notable is
      the continuing high number of patients suffering from severe injuries (AIS 3+) of
      the lower extremities.

PMID- 8736294
TI  - Preventable deaths among major trauma patients in Mersey Region, North Wales and
      the Isle of Man.
AB  - Preventable and unexpected deaths following injury were identified from among
      1088 victims of major injuries arising in a defined population and area during a
      12-month period. In hospital, 44 (16 per cent) deaths from blunt injury, one
      death from penetrating injury and one death from drowning were preventable. In
      patients sustaining blunt injuries, 22 per cent of non-head-injury deaths and 13
      per cent of head-injury deaths were preventable. In all preventable head-injury
      deaths either a delay in operation (35 per cent) or no operation for mass lesions
      (65 per cent) occurred, often because of misdiagnosis as alcohol intoxication (22
      per cent) or CVA (22 per cent). Multiple preventable factors were more likely in
      non-head-injury deaths and included missed injuries (67 per cent), poor airway
      care (57 per cent), delayed or no operation (52 per cent), undertransfusion (38
      per cent) and inadequate surgery (19 per cent). By TRISS methodology the outcome
      was unexpected, in 53 per cent blunt injury deaths in hospital and 2.8 per cent
      of survivors. Three preventable blunt injury deaths (6.8 per cent) had
      probabilities of survival < 50 per cent and were not, therefore, identified as
      unexpected by TRISS. A preventable death rate of 16 per cent for blunt injuries
      equates to 638 preventable blunt injury deaths each year in England and Wales.

PMID- 8736295
TI  - A mechanism for entrapment of the tibialis posterior tendon in lateral subtalar
      dislocation.
AB  - The entrapment of the tibialis posterior tendon causing a block to reduction of
      lateral subtalar dislocation is recognized. The mechanism which allows tendon
      excursion is less clearly understood. We present a case in which extensive
      tearing of the musculotendinous junction of the tibialis posterior muscle
      occurred during tendon displacement and entrapment in lateral subtalar
      dislocation. In view of this previously poorly recognized finding the two
      theories regarding entrapment are discussed. Recognition of the cause of the
      tendon lengthening with an intact flexor retinaculum allows appropriate early
      treatment.

PMID- 8736296
TI  - A comparison of isokinetics and muscle strength ratios following intra-articular
      and extra-articular reconstructions of the anterior cruciate ligament.
AB  - A prospective, randomized clinical trial was conducted to compare an intra
      articular with an extra-articular reconstruction of the anterior cruciate
      ligament. Isokinetic muscle testing was carried out 6 months to 2 years following
      operation using the Biodex isokinetic dynamometer. The extra-articular procedure
      resulted in a lower deficit for the peak quadriceps and hamstring torques and the
      range of motion.

PMID- 8736297
TI  - The epidemiology of pelvic fractures in the Mersey Region.
AB  - The Mersey Region Trauma Survey was performed over 12 months in 1989 and 1990 to
      study the epidemiology of trauma in a population of 3,200,000. All deaths from
      injuries, and all survivors with an injury severity score of 15 or over were
      included, giving a total of 1088 cases. This paper, primarily epidemiological,
      considers those victims with a pelvic fracture (153 patients), and especially
      those who reached hospital alive (111 patients). The epidemiology, hospital care
      and mortality are considered, but the specific management of individual fractures
      is not.

PMID- 8736298
TI  - The Florida trauma system: assessment of a statewide data base.
AB  - The State of Florida maintains a statewide trauma registry. This paper examines
      the data provided to the registry by four Level I, four Level II, and four non
      designated trauma care facilities within the state for completion. There were
      18,961 patients records in the registry between 1 July 1991 and 30 June 1992
      which were reviewed. Completed records were defined as containing appropriate
      notations for age, mechanism of injury, Glasgow Coma Scale, systolic blood
      pressure, respiratory rate, and Injury Severity Score. The mean completion rate
      in Level I facilities was 22.75 per cent, in Level II facilities it was 19.75 per
      cent and in non-designated centres it was 31.95 per cent. The deficits in
      completion may lead to errors in calculating trauma system efficacy, outcomes,
      and costs. Assigning and enforcing responsibility for completion of trauma
      registry data within individual facilities may aid in the resolution of these
      issues.

PMID- 8736299
TI  - Volar perilunate dislocation of the carpus: a case report and elucidation of its
      mechanism of occurrence.
AB  - Perilunate dislocation is a rare injury. The dorsal type, in which the distal row
      of the carpus displaces posterior to the lunate, is more common; the volar
      dislocation of the carpus on the lunate is an extremely rare injury. In addition
      to a case report of this rare injury, a probable mechanism is described with
      cadaveric studies. The proposed mechanism, to the author's best knowlege, has not
      been reported or recognized in the English literature, previously.

PMID- 8736300
TI  - Fracture of the thumb sesamoid: a new physical sign.

PMID- 8736301
TI  - Repair of neglected Achilles tendon ruptures with Marlex mesh.

PMID- 8736302
TI  - Selective embolization of pseudo-aneurysms of the renal artery after blunt
      abdominal injury in a patient with a single kidney.

PMID- 8736303
TI  - Juvenile Tillaux fracture of the ankle associated with a tibial shaft fracture: a
      unique combination.

PMID- 8736304
TI  - 'Sand-blaster' injuries.

PMID- 8736306
TI  - An atypical fracture of a triquetral-lunate synostosis.

PMID- 8736305
TI  - False aneurysm of the descending aorta due to penetrating injury.

PMID- 8736307
TI  - A potentially life-threatening upper eyelid laceration.

PMID- 8736308
TI  - New concept of microtubule dynamics and microtubule motor movement and new model
      of chromosome movement in mitosis.
AB  - In this study, microtubules are regarded as polymers with positive free surface
      energy. The dynamics of such polymers is complex, consisting of equilibrium, non
      equilibrium, and one-directional processes. This view of microtubules enables us
      to propose a new model of microtubule dynamics both in vitro and in vivo, and to
      draw a new conclusion on the role of GTP hydrolysis and calcium cations in
      microtubule polymerization. The study also offers a new model of chromosome
      movement in mitosis and a new model of the movement of motor proteins along
      microtubules. In the conclusion of the similarity and difference between
      microtubules and microfilaments is examined. We conclude that microfilaments,
      like microtubules, represent polymers with positive free surface energy, and that
      the movement of myosins along microfilaments can be realized in the same manner
      as the movement of motor proteins along microtubules.

PMID- 8736309
TI  - Polyribosome dynamics: size-distribution as a function of attachment,
      translocation and release of ribosomes.
AB  - Assembly of polyribosomes is the ubiquitous manifestation of the activation of
      translational machinery in cells. This is accompanied by a concomitant appearance
      of mRNAs either from an activation of pre-existing ribo-nucleoprotein particles
      (RNP) or from newly synthesized transcripts. The size-distributions of
      polyribosomes as inferred from their sedimentation profiles are essentially
      defined by various kinetic parameters responsible for continuous flux of
      ribosomes due to their recycling between the "free" and the "bound" states. In
      the theoretical analysis presented here the time-evolution of polyribosomes and
      their sustenance in the steady state is considered as a Markovian process with
      the states of mRNAs defined as the number of ribosomes attached. Expressions for
      the elements of one-step transition matrix as a function of kinetic parameters
      related to the initiation, translocation and the release of ribosomes and the
      size of mRNA are derived. The latter is shown to be relevant only in so far as it
      sets an upper limit to the size of polyribosomes. Implications of transient
      arrest of ribosomes at the initiation site as envisaged in the signal hypothesis
      for the synthesis of secretory proteins and the putative role of receptor
      mediated post-translational transport of proteins have been examined. Results of
      computer simulations on model systems have focussed attention on the diverse
      types of profiles that may appear under varying physiological conditions.

PMID- 8736310
TI  - Evolution of the genetic switch in temperate bacteriophage. I. Basic theory.
AB  - While the molecular mechanisms underlying lysogeny and induction in bacteriophage
      have been intensely studied, relatively little has been done to relate these
      findings to their presumed selective functions. To explore the ecological basis
      for these traits, I have used a resource-based model for competition between
      bacteriophage with different probabilities of lysogeny and different spontaneous
      induction rates. In any given habitat the fitness of a phage will depend on the
      inputs of sensitive cells and nutrient resources. In equable environments
      (modeled here using chemostats with constant inputs of nutrients and sensitive
      cells), bacteriophage with low probabilities of lysogeny and low induction rates
      can always invade when rare and will generally be good competitors. In variable
      environments (chemostats with seasonal inputs), bacteriophage with higher
      probabilities of lysogeny and higher induction rates are favored. In both equable
      and variable environments, the ability of a phage to invade when rare will depend
      on the properties of the resident phage, and it is possible for phages with
      divergent parameter values to coexist. The modeling suggests that bacteriophage
      that have evolved moderately low induction and lysogeny rates will be able to
      "hedge their bets" against environmental change without sacrificing the ability
      to compete well in a constant environment. Implications of this theory for
      understanding the molecular basis of gene regulation in temperate bacteriophage
      and other viruses are discussed.

PMID- 8736311
TI  - The analysis of limiting dilution assays conducted under non-saturating
      conditions.
AB  - A form of mathematical analysis is presented which permits an extended analysis
      of limiting dilution assays under conditions in which either accessory factors,
      or cells or both are limiting. This is in contrast to the traditional form of
      analysis which permits only a single limiting parameter. Both make use of in
      vitro experiments in order to determine the number of antibody-producing cell
      precursors: the traditional form of analysis requires that all accessory cells or
      their factors be present in saturating concentrations; whereas in the analytic
      method employed here, not only B cells, but also accessory cells (macrophages) or
      their factors may be limiting. Analysis under non-saturating conditions permits
      greater elucidation of the mechanisms of intercellular interaction.

PMID- 8736312
TI  - A critique of published studies into the effects of amateur boxing: why is there
      a lack of consensus?

PMID- 8736313
TI  - Medical Support Troop 3, Split Croatia. Tri-service and international.

PMID- 8736314
TI  - Thrombophilia: some recent advances in understanding.
AB  - Thrombophilia is a term with many definitions although the majority include
      criteria such as thrombosis under the age of 45; recurrent thromboembolism and a
      positive family history. It reflects a disturbance in the normal delicate balance
      between pro- and anti-coagulation such as to favour inappropriate thrombosis.
      This review concentrates on the newly described phenomenon of activated protein C
      resistance while reviewing the natural anticoagulant system. It will also briefly
      examine the indications for 'thrombophilia' screening and the implications for
      individuals found to have an abnormality of their natural anticoagulants.

PMID- 8736315
TI  - Non-union of ankle fractures in patients with ipsilateral foot drop.
AB  - We report two cases of non-union of closed ankle fractures in patients with
      neurologically compromised ipsilateral lower limbs, which we believe to be the
      first description of this association in the English language.

PMID- 8736316
TI  - Submarine escape from a depth of 300 feet: a personal experience.

PMID- 8736317
TI  - Medical protection for serving medical officers.

PMID- 8736318
TI  - Care of World War II convoy casualties in the Kola area of North Russia. Part 1-
      initial arrangements.

PMID- 8736319
TI  - Leukaemia inhibitory factor is expressed by normal human keratinocytes in vitro
      and in vivo.
AB  - Leukaemia inhibitory factor (LIF) is a pleotropic cytokine, regulating
      differentiation, cell growth, cachexia and inflammation. Using the reverse
      transcription-polymerase chain reaction (RT-PCR) we found that, in culture,
      normal human keratinocytes (KC) expressed mRNA transcripts for both LIF and the
      LIF receptor. In the conditioned medium (CM), constitutive LIF protein production
      was barely detectable but stimulation of KC with 10 ng/ml of either interleukin
      (IL)-1 alpha, or IL-8, for 24 h, resulted in small but significant increases (P <
      0.05) in LIF protein, as measured by enzyme-linked immunosorbent assay. After
      culture in media containing 1.5 mmol/l calcium, a time-dependent increase in LIF
      mRNA was seen up to 72 h (an 8.5-fold increase), over levels in cells cultured in
      0.05 mmol/l calcium. A large increase in LIF protein in the CM (from 1.15 +/-
      0.15 pg/ml to 178.7 +/- 75.7 pg/ml) was seen 72 h after a switch to media
      containing 1.5 mmol/l calcium (P = 0.05). Twenty-four hours after stimulation of
      human KC in culture with 10 ng/ml recombinant LIF, a twofold increase in both IL
      1 alpha and IL-8 protein in the CM (P < 0.05) was observed. In normal human scalp
      and foreskin, the epidermis was shown to contain LIF protein by immunostaining.
      LIF staining was found throughout the epidermis, and in the cells of the outer
      layer of the root sheath. Thus, KC synthesize LIF in vitro and in vivo.

PMID- 8736320
TI  - Ultraviolet B-exposed major histocompatibility complex class ii positive
      keratinocytes and antigen-presenting cells demonstrate a differential capacity to
      activate T cells in the presence of staphylococcal superantigens.
AB  - In this study we tested the capacity of ultraviolet B (UVB)-irradiated major
      histocompatibility complex (MHC) class II+ keratinocytes, monocytes and dendritic
      cells to activate T cells in the presence of Staphylococcus enterotoxin B. We
      demonstrated that UVB irradiation of MHC class II+ keratinocytes does not change
      their capacity to activate T cells in the presence of Staphylococcus enterotoxin
      B. In contrast, UVB irradiation of antigen-presenting cells decreases their
      capacity to activate T cells. This differential capacity to activate T cells
      after UVB irradiation was not due to factors released from UVB-irradiated cells.
      The interferon-gamma induced upregulation of HLA-DR and intercellular adhesion
      molecule-1 on keratinocytes does not seem to be the only explanation, since UVB
      irradiation decreased the accessory cell function of interferon-gamma pretreated
      monocytes. Differential requirements for and UVB regulation of costimulatory
      molecules may be involved, since blocking of the B7/CD28 pathway affects the
      capacity of dendritic cells but not keratinocytes to activate T cells in the
      presence of Staphylococcus enterotoxin B. Thus, MHC class II+ keratinocytes in
      the presence of superantigens released from staphylococci may activate T cells
      and maintain inflammation despite UVB treatment.

PMID- 8736321
TI  - Culture and drug biotransformation capacity of adult human keratinocytes from
      post-mortem skin.
AB  - The aim of this study was to analyse viability, growth, differentiation and drug
      metabolic capacity of cultured human keratinocytes obtained from post-mortem
      skin. Epidermal cells were prepared from 1-day post-mortem paired sun-exposed
      (outer) and sun-protected (inner) sites of the upper arm, of donors aged 47-80
      years. The percentage of viable cells obtained from post-mortem skin was only
      slightly lower than that usually obtained for keratinocytes isolated from fresh
      skin, and no alterations of epidermal markers were noted. Keratinocytes isolated
      post-mortem from non-exposed skin had a higher viability (78 versus 73%), and a
      more active proliferation, while their attachment rate, keratin composition,
      lipid synthesis capacity and transglutaminase activity levels were similar to
      those of epidermal cells obtained from the sun-exposed skin. Keratinocytes
      isolated from post-mortem skin expressed various phase I and II activities at
      levels similar to those obtained with keratinocytes isolated from fresh skin
      while drug metabolizing enzyme activities were consistently higher in sun-exposed
      compared to sun-protected cells. The results support the conclusion that skin
      collected post-mortem can represent an alternative source of viable and
      functional epidermal cells, and that the functional changes that occur in adult
      keratinocytes habitually exposed to the sun, affect much more strongly the drug
      metabolism capacity than the expression of differentiation markers.

PMID- 8736322
TI  - A comparison of techniques to assess skin blanching following the topical
      application of glucocorticoids.
AB  - Glucocorticoid-induced dermal blanching provides a useful research tool to study
      steroid potency and sensitivity. Conventional measurement of the intensity of
      blanching relies on subjective assessment by a trained observer using a visual
      score. Several objective techniques have recently been reported to detect skin
      blanching, but their sensitivity has not been compared previously with subjective
      visual recordings. In this report we aimed to establish whether objective methods
      offer sufficient sensitivity to be employed in epidemiological studies of
      glucocorticoid responsiveness. In healthy subjects we applied beclomethasone
      dipropionate at three concentrations (1, 10 and 100 micrograms/ml) under an
      occluded dressing overnight. The following morning we measured blanching using a
      visual score, laser Doppler velocimetry with the MBF 3D monitor (Moor Instruments
      Ltd, U.K.) and a perfusion imager (Lisca, Sweden), and reflectance
      spectrophotometry with the Dia-Stron 'erythemameter'. Using the visual score,
      blanching was detected at all concentrations of steroid. Neither laser Doppler
      instrument detected vasoconstriction at any concentration. By contrast, the
      reflectance spectrophotometer successfully recorded blanching at 10 and 100
      micrograms/ml, but not at 1 microgram/ml. We conclude that laser Doppler
      instruments, including the novel scanning perfusion imager, do not detect
      glucocorticoid-induced skin blanching, perhaps because it reflects venular rather
      than arteriolar vasoconstriction. By contrast, the Dia-Stron reflectance
      spectrophotometer has sufficient sensitivity to be used as an alternative to
      visual assessment in epidemiological studies of human glucocorticoid-induced
      dermal blanching.

PMID- 8736323
TI  - Clinical significance of serum levels of soluble interleukin-2 receptor in
      patients with localized scleroderma.
AB  - Localized scleroderma has been reported to be accompanied by abnormal immune
      reactions, including autoantibody production and lymphocyte activation.
      Lymphocyte activation can be quantitatively detected by measuring soluble
      interleukin-2 receptor (sIL-2R) in serum samples. In this study, serum sIL-2R
      levels were assayed by a sensitive enzyme-linked immunosorbent assay, in 48
      patients with localized scleroderma, in 20 with systemic sclerosis (SSc) and in
      20 healthy controls. Serum levels of sIL-2R were significantly higher in patients
      with localized scleroderma than in healthy controls. The serum levels of sIL-2R
      were correlated with the number of sclerotic lesions, the number of involved
      areas, the levels of anti-ssDNA, and the levels of antihistone antibody
      immunoglobulin M. Moreover, sIL-2R levels in sera from patients with SSc were
      also significantly higher than in healthy controls. Elevated serum levels of sIL
      2R in localized scleroderma suggest that lymphocyte activation is one of the
      early processes in the development of this disease.

PMID- 8736324
TI  - Specificity of antinuclear antibodies in scleroderma-like chronic graft-versus
      host disease: clinical correlation and histocompatibility locus antigen
      association.
AB  - Chronic graft-versus-host disease after bone marrow transplantation presents, in
      a few cases, as mild to severe scleroderma-like changes. Patients with chronic
      graft-versus-host disease with and without sclerodermatous skin changes were
      analysed for antinuclear autoantibodies (ANA) and antinucleolar autoantibodies
      (ANoA) and the results correlated with disease symptoms and histocompatibility
      locus antigen (HLA) pattern. Nineteen patients with chronic graft-versus-host
      disease and scleroderma-like skin changes, 18 with chronic graft-versus-host
      disease without scleroderma, and 17 controls on immunosuppressive treatment were
      screened for ANA and ANoA using enzyme-linked immunosorbent assay,
      immunodiffusion and immunoblot techniques. Four patients with severe scleroderma
      had antibodies to topoisomerase I, two had antibodies against PM-Scl, both
      characteristic serological findings in idiopathic systemic scleroderma. One
      patient had La/SSB antibodies and, in three cases, antibodies to the nucleolar
      antigen C23 (nucleolin) could be identified. A possible correlation between
      antinucleolin antibodies and disease activity was observed. HLA-A1, -B1, and -B2
      were found significantly more often in patients with scleroderma-like symptoms in
      comparison to patients without scleroderma-like symptoms. Chronic graft-versus
      host disease with scleroderma-like manifestations can be associated with the
      occurrence of ANA specific for idiopathic scleroderma. The development of
      scleroderma after bone marrow transplantation might have a HLA-linked genetic
      background.

PMID- 8736325
TI  - The use of antibody to C5b-9 in the subclassification of lupus erythematosus.
AB  - Fifty-five patients with biopsy-proven cutaneous lupus erythematosus (LE) were
      identified in whom a prospective and retrospective review of the clinical and
      laboratory data allowed subclassification into systemic (SLE), subacute (SCLE),
      or discoid (DLE) variants. In addition to conventional direct immunofluorescence,
      an indirect immunofluorescent technique, using a monoclonal antibody, was
      employed to assess deposition of the membranolytic attack complex (C5b-9) in skin
      lesions. Deposition of C5b-9 within the epidermis correlated with a diagnosis of
      SCLE with or without antibodies to Ro and was seen in SLE patients with
      antibodies to extractable nuclear antigens Ro, La, Sm, and RNP, and in DLE
      patients with positive antinuclear antibodies and/or extracutaneous
      manifestations. In the SLE group, vascular C5b-9 deposition was present in six
      patients. Of these, four had circulating lupus anticoagulant, one had lymphocytic
      vasculitis, and two had antibodies to Ro. In two patients with SLE there was
      keratinocyte decoration for immunoglobulin G but not for C5b-9, in the absence of
      seropositivity for antibodies to Ro, La, Sm, and ribonucleoprotein (RNP). The
      immunohistological examination of skin lesions using a monoclonal antibody to C5b
      9 is a valuable adjunct in the subclassification of LE. The presence of C5b-9
      within skin lesions of patiens with LE implies a pathogenic role for complement
      mediated pore formation.

PMID- 8736326
TI  - Reduced collagenase gene expression in fibroblasts from hypertrophic scar tissue.
AB  - The major histopathological feature of hypertrophic scar lesions is fibrosis,
      characterized by excessive accumulation of collagen. The purpose of this study
      was to determine if there is not only increased expression of collagen but also
      decreased expression of collagenase in hypertrophic scar fibroblasts. We compared
      the expression of mRNA for alpha 1 (I) and alpha 1 (III) collagen, and
      collagenase in cultured fibroblasts from different portions of hypertrophic scars
      and normal dermis. In hypertrophic scar fibroblasts, increased levels of alpha 1
      (I) and alpha 1 (III) collagen mRNAs were observed in fibroblasts from the edge
      and outside of scar tissue, while normal levels were noted in fibroblasts from
      the centre of this tissue. In contrast, decreased levels of collagenase mRNA were
      found in the hypertrophic scar fibroblasts. The reductions were: centre (25% of
      the control) greater than the edge (43% of the control) greater than the outside
      (84% of the control). The changes in the collagenase mRNA levels of the
      hypertrophic scar fibroblasts correlated well with decreased collagenolytic
      activity as determined by the degradation rate of fluorescein isothiocyanate
      labelled type I collagen in fibroblast culture supernatant. These results suggest
      that decreased expression of collagenase in hypertrophic scar fibroblasts may be
      one possible cause for the excessive accumulation of collagen in the skin lesions
      of hypertrophic scars.

PMID- 8736327
TI  - Topical diphencyprone for alopecia areata: evaluation of 48 cases after 30
      months' follow-up.
AB  - Forty-eight patients (23 male, 25 female) with severe alopecia areata were
      sensitized and treated with topical diphencyprone. Thirty-eight per cent of the
      subjects had good regrowth of hair at a mean follow-up period of 30.8 months. The
      presence of nail changes, a personal history of atopy and a long duration of
      alopecia had an adverse prognostic effect.

PMID- 8736328
TI  - Gastrostomy and growth in dystrophic epidermolysis bullosa.
AB  - Chronic malnutrition and growth failure are features of severe dystrophic
      epidermolysis bullosa (DEB). Conventional dietetic intervention is of limited
      benefit. Oesophageal dilatation or reconstruction to alleviate stricture is
      associated with substantial risks. Surgical placement of a feeding gastrostomy is
      a comparatively straightforward procedure, provided that specialized anaesthetic
      and surgical techniques are employed. Gastrostomy insertion was undertaken in 18
      children with severe DEB and the effects of this intervention were
      retrospectively evaluated. The majority received button devices (inserted
      primarily) and gastrostomy feeding supplemented oral intake. One year
      postoperatively, the average increase in weight standard deviation scores (SDS)
      of 13 patients was 0.9 SDS (95% confidence interval 0.44, 1.35) and in height
      0.42 SDS (95% confidence interval 0.05, 0.79). One patient developed an
      incisional hernia and four patients experienced minor leakage around the
      gastrostomy entry site. Two patients never accepted their gastrostomies, which
      were therefore removed. Two further patients died for reasons unrelated to the
      procedure. Our observations suggest that gastrostomy feeding can play a valuable
      role in severe DEB and is associated with minimal morbidity. Such intervention is
      best undertaken before growth failure is established, and prior to puberty.

PMID- 8736329
TI  - Ferrochelatase activities in patients with erythropoietic protoporphyria and
      their families.
AB  - Ferrochelatase, estimated as zinc chelatase, was measured in the lymphocytes of
      30 patients with erythropoietic protoporphyria (EPP), in 35 first- or second
      degree relatives of patients with EPP, and in 50 healthy controls. In 30 EPP
      patients the zinc chelatase level (mean +/- standard deviation, SD) was 0.45 +/-
      0.10 nmol of zinc protoporphyrin per hour per milligram of protein, in 14 EPP
      carriers the zinc chelatase level (mean +/- SD) was 0.42 +/- 0.09 and in 50
      healthy controls the zinc chelatase level (mean +/- SD) was 0.84 +/- 0.27. All
      patients with EPP were also demonstrated to have an elevated protoporphyrin level
      in their red blood cells: the erythrocyte protoporphyrin levels were as follows
      EPP patients (mean +/- SD) 1300 +/- 758 nmol protoporphyrin/dl, EPP carriers
      (mean +/- SD) 60 +/- 24, and healthy controls (mean +/- SD) 50 +/- 25 (P < 0.001
      for EPP patients compared to controls and EPP carriers). The families of 12 out
      of 15 EPP patients were examined with respect to the mode of inheritance of the
      disorder. Of 35 relatives, 14 were carriers of EPP, as characterized by reduced
      zinc chelatase activity in lymphocytes and by a normal protoporphyrin level in
      red blood cells. None of the 14 EPP carriers had presented with clinical symptoms
      of EPP. The mod of inheritance was autosomal dominant in seven of the 12 examined
      families, and autosomal recessive in two. In two families only one parent could
      be investigated, but we nevertheless concluded that the inheritance was autosomal
      dominant. Inheritance in one EPP family could not be elucidated as both parents
      showed normal zinc chelatase levels and did not demonstrate abnormal erythrocyte
      protoporphyrin levels.

PMID- 8736330
TI  - Multiple basal cell carcinomas: no association with HLA-DRB, HLA-DQA1 or HLA-DQB1
      in Swedish patients.
AB  - Many diseases with autoimmune features are associated with alleles of the human
      leucocyte antigen (HLA). However, few if any malignant disorders have
      reproducibly been shown to be HLA-associated. In three independent studies, using
      serological tissue typing techniques, an increase of the HLA class II specificity
      DR1 has been found in patients with multiple basal cell carcinomas. These
      observations prompted us to determine the frequencies of DRB1, DQA1, and DQB1
      alleles by high-resolution genomic tissue-typing methods, including subdivision
      of the serological DR1 specificity in the four sequence-defined alleles,
      DRB1*0101 to DRB1*0104, in 50 unrelated Swedish patients with a history of four
      or more basal cell carcinomas and 250 healthy controls. The frequency of DR1 was
      the same in patients and controls (18%). All DR1-positive patients and controls
      carried the DQA1*0101 and DQB1*0501 alleles. Six of the nine DR1-positive
      patients and controls carried the DQA1*0101 and DQB1*0501 allels. Six of the nine
      DR1-positive patients were DRB1*0101-positive, one DRB1*0102 and two carried the
      DRB1*0103 allele. This distribution of DRB1*01 alleles did not differ from the
      one found in the controls. We conclude that genetic factors associated with the
      HLA class II region do not contribute significantly to the aetiology of multiple
      basal cell carcinomas.

PMID- 8736331
TI  - Are stress proteins induced during PUVA therapy?
AB  - Heat shock or stress proteins are produced in practically all cell types when
      they are exposed to temperatures a few degrees above normal. Measurement of the
      skin temperature of patients undergoing psoralen and ultraviolet A (PUVA) cabinet
      treatment for psoriasis revealed that the outer layers of the skin experience a
      mean temperature rise of 5.3 degrees C. However, this did not produce a
      detectable stress response in epidermal samples taken after PUVA treatment. In
      vitro exposure of epidermis from biopsies or of cultured keratinocytes to a 5-7
      degrees C temperature rise produced a heat shock response, as measured by an
      increase in the production of proteins of the HSP90 and HSP70 families. These
      results were confirmed by the use of specific monoclonal antibodies. The
      corresponding mRNAs were also analysed using labelled probes. In an in vitro
      system, following simulated PUVA treatment of cultured keratinocytes, increases
      in the synthesis of HSP90 and HSP70 were detected but these increases did not
      correlate with changes in mRNA levels.

PMID- 8736332
TI  - The prevalence of dermatophyte infection in well-controlled diabetics and the
      response to Trichophyton antigen.
AB  - The prevalence of dermatophyte infection was assessed in 100 patients with well
      controlled insulin-dependent diabetes, and in a control group of 100 non
      diabetics matched for age, sex, occupation and sporting activity. Immediate and
      delayed responses to intradermal testing with Trichophyton antigen were recorded
      in both groups. The overall infection rate (skin and nails) was 19% in diabetics
      and 17% in controls. There was a higher infection rate in the skin of diabetics
      (17%) than in controls (8%), but this was not significant. Nail infection was
      seen in 12% of diabetics and in 11% of controls. Intradermal testing with
      Trichophyton antigen gave a higher proportion of both immediate and delayed
      positive results in diabetics. However, more control patients showed only an
      immediate positive response or only a delayed one. There was no evidence of an
      increased infection rate in those with immediate positive responses or of
      diminished infection rates in those with delayed positive responses, and no
      correlation with oral Candida infection. These findings applied equally to
      diabetics and controls.

PMID- 8736333
TI  - Effect of topical cis-urocanic acid on local lymph node activation during contact
      sensitization in mouse, rat and guinea-pig.
AB  - Cis-urocanic acid (cUCA) has been suggested as a mediator of impairment of
      contact hypersensitivity induction by ultraviolet B (UVB) irradiation. We
      ascertained whether topical cUCA influences local lymph node activation during
      induction of contact hypersensitivity. Topical cUCA or vehicle was applied during
      the local lymph node assay to oxazolone. Local lymph node weight and cell number
      were assessed in all animals. Additionally, cell proliferation rate was studied
      in Hartley guinea-pigs and CBA/Ca mice, whereas activation of antigen-presenting
      cells was quantified in NMRI mice and Wistar rats. Topical cUCA suppressed all
      parameters of local lymph node activation due to oxazolone application in guinea
      pigs. No effect, with the exception of a suppression of antigen-presenting cell
      activity, was seen in mice. No effect was seen in rats. The study shows that
      topical cUCA may suppress local lymph node activation during contact
      sensitization and suggests that differences between the effect of cUCA in
      different animal species may exist.

PMID- 8736334
TI  - Allergic contact dermatitis from latex rubber.
AB  - Previously we have found occasional patients with delayed hypersensitivity to
      latex (in rubber gloves) in the absence of allergy to any chemicals in the rubber
      chemical screen. There are many reports of contact urticaria to latex and
      isolated reports of delayed hypersensitivity to latex, usually in the presence of
      contact urticaria. To establish if latex ruber is a more common cause of delayed
      hypersensitivity than is currently recognized, we patch tested all patients
      attending our contact dermatitis clinic, over a 6-month period, with latex. Of
      822 patients, 16 (1.9%) demonstrated positive cutaneous reactions to latex. Six
      exhibited contact urticaria to latex, five contact urticaria and allergic contact
      dermatitis, and five allergic contact dermatitis alone. Of the five with delayed
      hypersensitivity to latex in the absence of contact urticaria, only one was
      atopic and the sensitivity was thought to be relevant or possibly relevant in
      four. Of our patients, 1.2% exhibited positive patch-test reactions to latex.
      Patch testing with latex should be considered where contact dermatitis to a latex
      rubber-containing product is suspected, e.g. gloves and footwear.

PMID- 8736335
TI  - Leucocytoclastic vasculitis induced by prolonged exercise.
AB  - Many people develop skin symptoms after long-distance walks, but little is known
      about the aetiology of these. In this study we took 11 biopsies from 10 long
      distance walkers who walked 80 km. All biopsies originated from purpuric lesions
      on the lower legs, which had appeared during walking. In all 11 specimens, signs
      of a leucocytoclastic vasculitis were present with leucocytoclasis, exocytosis of
      erythrocytes and a granulocyte/mononuclear perivascular infiltrate.
      Immunofluorescence investigations showed deposition of C3c in many specimens and
      immunoglobulin M in some. The occurrence of a leucocytoclastic vasculitis after
      prolonged exercise may be explained by the existence of an exercise altered
      cutaneous microcirculation, complement activation and an altered immune function.

PMID- 8736336
TI  - Hypergammaglobulinaemic purpura of Waldenstrom and Ro/SSA autoantibodies.
AB  - Seven out of nine patients (78%), seen over a 13-year period with
      hypergammaglobulinaemic purpura of Waldenstrom were found to have antibodies to
      Ro/SSA. Over this period we saw 175 patients who had antibodies to Ro/SSA. In six
      of the seven patients, associated diseases were recognized. Five had Sjogren's
      syndrome, and one had systemic lupus erythematosus with Sjogren's syndrome and
      thyroiditis (and died 19 years after initial presentation from cerebral
      infarction). Screening for antibodies to Ro/SSA is important in the diagnosis of
      patients with hypergamma-globulinaemic purpura, and is helpful in predicting
      prognosis.

PMID- 8736337
TI  - Dermatological presentation of disease associated with antineutrophil cytoplasmic
      antibodies: a report of two contrasting cases and a review of the literature.
AB  - Antineutrophil cytoplasmic antibody (ANCA)-associated disease (AAD) constitutes a
      pathological disease spectrum of a necrotizing vasculitis of small- and medium
      sized vessels, extravascular granuloma formation, and necrotizing and crescentic
      glomerulonephritis, and also a clinical disease continuum which ranges from renal
      limited disease to a widespread systemic vasculitis, including Wegener's
      granulomatosis and microscopic polyangiitis. In the latter, circulating ANCA are
      an aid to diagnosis and also may play a pathogenic part. Two contrasting patients
      with AAD are described, both of whom presented primary with dermatological
      features. These included a cutaneous purpuric vasculitis, orogenital ulceration,
      infarction of the fingertip, and pyoderma gangrenosum-like ulceration. These
      cases will familiarize dermatologists with both the concept and dermatological
      features of AAD.

PMID- 8736338
TI  - Bullous pemphigoid complicating human orf.
AB  - We report five cases of human orf complicated by bullous pemphigoid. This is a
      previously unrecorded complication of orf. Knowledge of the association allows
      for better management in the affected patient.

PMID- 8736339
TI  - Successful treatment of bullous pemphigoid with pulsed intravenous
      cyclophosphamide.
AB  - Pulsed therapy with intravenous cyclophosphamide was successful in a patient with
      bullous pemphigoid whose disease had proved resistant to other treatments.

PMID- 8736340
TI  - An acquired bullous dermatosis due to an autoimmune reaction against uncein.
AB  - A 59-year-old male showed acquired, mechanically induced, scarring blisters on
      the fingers, toes, scalp and abdomen, as well as in the oral cavity.
      Ultrastructural and immunohistochemical examination of the bullae revealed
      junctional epidermal-dermal separation and IgG deposits in the lamina lucida of
      the basement membrane zone (BMZ), where the reactivity of the 19-DEJ-1 monoclonal
      antibody was decreased. Anti-BMZ autoantibodies detected in his serum were
      reactive to the lower lamina lucida region of normal human skin. SDS-PAGE of
      affinity purified antigens from human keratinocytes with IgG from the patient's
      serum revealed three polypeptide bands at 165, 135 and 100 kDa, in reduced
      condition. The indirect immunofluorescence test of his serum was negative on skin
      cryosections from patients with lethal junctional epidermolysis bullosa.
      Pretreatment of normal human skin sections with the patient's serum, blocked the
      binding of 19-DEJ-1 monoclonal antibody but not that of the GB3 monoclonal
      antibody. This case is considered to be an acquired autoimmune bullous dermatosis
      due to an autoantibody reaction against uncein (19-DEJ-1 antigen), a component of
      anchoring filaments.

PMID- 8736341
TI  - Hereditary palmoplantar keratoderma with deafness.
AB  - A pedigree showing the uncommon association of palmoplantar keratoderma with
      sensorineural deafness is described.

PMID- 8736342
TI  - Black breast milk due to minocycline therapy.
AB  - We report the unusual case of a 29-year-old female who developed black
      discoloration of breast milk 3 weeks after commencing oral minocycline therapy
      for acne vulgaris. Histochemical analysis of the breast milk revealed the
      presence of pigment particles within macrophages with iron staining
      characteristics. We propose that the pigment may represent an iron chelate of
      minocycline or one of its derivatives.

PMID- 8736343
TI  - Oral papillary plasmacytosis cleared by radiotherapy.
AB  - We report a case of oral papillary plasmacytosis which initially responded well
      to etretinate and, subsequently, was successfully treated with radiotherapy, with
      minimal side-effects.

PMID- 8736344
TI  - Perforating plate-like osteoma cutis in a man with solitary morphoea profunda.
AB  - Solitary morphoea profunda is an unusual form of scleroderma, characterized by
      marked fibrosis, hyalinization of collagen fibres, and inflammatory cell
      infiltration in the deep dermal and subcutaneous layers. We describe a 58-year
      old man showing solitary morphoea profunda. Plate-like osteoma cutis, with
      transepidermal elimination of bony material, within the morphoea profunda, was
      present.

PMID- 8736345
TI  - Keloidal basal cell carcinoma. A new clinicopathological variant of basal cell
      carcinoma.
AB  - Basal cell carcinoma is the commonest malignant neoplasm of the skin. Clinical
      and histopathological variants are well known. We describe two patients with
      nodular lesions on the face, clinically suggestive of keloids, but with no
      previous history of injury at that site. Histopathological study, in both cases,
      demonstrated characteristic basaloid neoplastic aggregations of basal cell
      carcinoma, intermingled with thick, sclerotic, keloidal collagen bundles in the
      stroma. This peculiar stroma is responsible for the clinical and
      histopathological characteristics. We propose the name of keloidal basal cell
      carcinoma for this striking and distinctive variant of basal cell carcinoma.

PMID- 8736346
TI  - Ectopic extramammary Paget's disease affecting the upper abdomen.
AB  - We present 57-year-old man in whom ectopic extrammary Paget's disease (EMPD)
      affected the upper abdomen. Although the clinical appearance was suggestive of
      Bowen's disease or superficial basal cell epithelioma (BCE), the biopsy specimen
      showed EMPD histologically. Only 12 cases of ectopic EMPD have been reported
      (including this case). In our 20 year experience of 129 EMPD, this is the first
      ectopic case. Thus, the frequency of ectopic EMPD is 0.78% (one of 129) in our
      study. The male/female ratio in the reported 12 cases is 2: 1, nearly the same as
      EMPD in general (2.1: 1, in our 129 cases). The mean age of the 12 patients is
      65.8 years, which is not significantly different from ordinary EMPD (66.4 years,
      in our 129 cases). Comparing ectopic EMPD to ordinary EMPD, clinically and
      histologically, we could find no difference. As they appear to be the same
      disease, ectopic and ordinary EMPD may share similar origins and mechanisms of
      occurrence. We support the hypothesis that Paget's cells originate from the
      remaining pluripotential germinative cells which are able to differentiate into
      many kinds of secreting glands.

PMID- 8736347
TI  - Staphylococcal scalded skin syndrome in an HIV-1 seropositive man.
AB  - The staphylococcal scalded skin syndrome (SSSS) is very rare in adults. Renal
      impairment and immunocompromise are predisposing causes. We report a 38-year-old
      HIV-1 seropositive intravenous drug abuser who developed SSSS due to
      staphylococcal pneumonia. An exfoliating toxin-releasing Staphylococcus aureus,
      phage type II type 3C, was isolated from the sputum and from blood cultures. This
      is the third case of adult SSSS to be reported in the context of HIV disease.

PMID- 8736348
TI  - Kaposi's sarcoma with primary bone lesions in an HIV-seronegative man.
AB  - Classic Kaposi's sarcoma, with primary bone lesions, is described in an HIV
      seronegative man. The bone involvement, painful lytic lesions in the right leg
      and both feet, was shown by magnetic resonance and histology not to be contiguous
      with the skin lesions. Chemotherapy with vinblastine and doxorubicin,
      significantly reduced the skin and bone lesions, and pain also improved.

PMID- 8736349
TI  - Milia en plaque.
AB  - A 59-year-old woman presented with milia grouped in plaques, in the preauricular
      areas, bilaterally. Follicle-damaging dermatoses, tumours and external agents,
      can lead to this peculiar clinical pattern. We outline the clinical and
      histological features which allow accurate diagnosis of this condition.

PMID- 8736350
TI  - Acrolocalized acquired cutis laxa.
AB  - A 55-year-old man presented with a 14-year history of loose, redundant skin on
      the palmar aspects of the finger tips and toe pulps, which gave a peculiar
      'chewing gum' appearance. Skin biopsies of involved areas showed a normal
      appearance, and only a discrete decrease in the elastic fibres could be
      identified with an elastic tissue stain. Ultrastructural examination, however,
      demonstrated marked fragmentation and degeneration of the elastic tissue.
      Localized cutis laxa in an acral distribution, was fully developed at
      presentation. He gave a history of repeated episodes of swelling and urticaria of
      the involved areas, which we regard as being the initial inflammatory stages of
      this disease process.

PMID- 8736351
TI  - Erythropoietic protoporphyria.

PMID- 8736352
TI  - Pustulosis palmoplantaris associated with chronic recurrent multifocal
      osteomyelitis of the mandible.

PMID- 8736353
TI  - Specific cutaneous involvement in B-cell prolymphocytic leukaemia.

PMID- 8736355
TI  - Familial atrophia maculosa varioliformis cutis.

PMID- 8736354
TI  - Monitoring of the disease progress in Sezary syndrome by cd7- cells using flow
      cytometry.

PMID- 8736356
TI  - Detection of human papillomavirus type 16 DNA in two cases of verrucous carcinoma
      of the foot.

PMID- 8736357
TI  - Eccrine squamous syringometaplasia in intertriginous areas.

PMID- 8736358
TI  - Recurrent adenocarcinoma of the ovary presenting as skin nodules.

PMID- 8736359
TI  - Paraneoplastic pemphigus: potential therapeutic effect of plasmapheresis.

PMID- 8736360
TI  - Acitretin-induced myopathy.

PMID- 8736361
TI  - Urticarial vasculitis induced by centrally acting appetite suppressants.

PMID- 8736362
TI  - Intrathoracic lymphoproliferative disorders and lymphoma.
AB  - The spectrum of lymphoproliferative disorders is truly a continuum from benign
      diseases to malignant aggressive lymphomas. Remarkable advances in laboratory
      techniques of monoclonal antibody production and molecular biology over the last
      decade allow more sophisticated analysis of these diseases. It is now apparent
      that some entities previously labeled "benign" are actually non-Hodgkin's
      lymphomas. We review the current knowledge of this spectrum including the
      histopathologic and clinical findings, as well as the radiographic
      characteristics. Understanding the diseases, treatment challenges, and follow-up
      requirements aids the radiologist in a more efficient and cost-effective
      evaluation of these patients.

PMID- 8736363
TI  - Progressive burn injury documented with vimentin immunostaining.
AB  - Precise determination of burn depth during the immediate postburn period remains
      an unresolved clinical problem. In an attempt to provide a new clinical option to
      aid in diagnosis of burn depth, an immunohistochemical marker (antivimentin) was
      used to examine excisional tissues or serial punch biopsies, or both, in partial
      thickness human burn injuries. To test the hypothesis that burn injury continues
      to progress beyond the first 24 hours, burn depth was assessed by quantitative
      morphometric analysis in both a partial-thickness porcine burn model and in
      sequential samples from human patients. Vimentin immunostaining of ubiquitous
      mesenchymal populations resulted in a precise demarcation between burn eschar and
      the viable underlying dermis at 1 to 5 days after burn trauma. Porcine wounds
      showed continuous and significant progression in burn depth during days 1 through
      3, but wounds were no deeper on the fourth postburn day. Similarly, 13 of 14
      patients showed significant progression in burn depth between 1 to 5 days after
      burn injury. In conclusion, immunohistochemical staining with an antisera
      targeted toward a widely dispersed cell population in the dermis can be utilized
      as an effective tool to confirm the depth of tissue injury during the acute
      postburn period. Data from our randomly selected patients with partial-thickness
      burn suggest that burn wounds continue to demarcate for several days.

PMID- 8736364
TI  - Effects of an arginine-glycine-aspartic acid peptide-containing artificial matrix
      on epithelial migration in vitro and experimental second-degree burn wound
      healing in vivo.
AB  - Cells central to dermal tissue repair such as dermal fibroblasts and
      keratinocytes interact with arginine-glycine-aspartic acid (RGD)-containing
      proteins of the extracellular matrix such as fibronectin. It has been shown that
      synthetic peptides containing this RGD sequence can also support cell attachment
      and migration in vitro. We therefore set out to test whether the use of these
      peptides, when formulated as a synthetic RGD-peptide matrix consisting of peptide
      complexed with hyaluronic acid, would have an effect on the rate of epithelial
      migration and healing of experimental wounds. Evaluation consisted of measuring
      he extent of epithelial outgrowth from human dermal explants and the
      epithelization of experimental second-degree burn wounds in pigs. We show here
      that the RGD-peptide matrix supports epithelial sheet migration from explants in
      a dose-dependent manner. In second-degree burn wounds in pigs, wounds treated
      with daily applications of the RGD-peptide matrix under occlusion resurfaced at a
      significantly faster rate (day 7 = 57% completely epithelized) than wounds
      treated with hyaluronic acid under occlusion (day 7 = 13% completely epithelized,
      p < 0.01), occlusion alone (day 7 = 13% completely epithelized, p < 0.01), or air
      exposed (day 7 = 0% completely epithelized, p < 0.001). Histologic examination
      showed that wounds treated with the RGD-peptide matrix also had thicker
      epithelial covering and greater granulation tissue deposition than occluded, air
      exposed, and hyaluronate-treated wounds. These data therefore show that the use
      of RGD-peptide matrix induces faster explant epithelial migration and results in
      faster healing of experimental second-degree burns.

PMID- 8736365
TI  - Reduced albumin extravasation in experimental rat skin and muscle burn injury by
      D-myo-inositol-1,2,6-trisphosphate treatment.
AB  - This study investigated the effects of the anti-inflammatory agent D-myo-inositol
      1,2,6-trisphosphate (IP3) on burn edema. Two sets of experiments were performed.
      In the first set, a full-thickness burn injury was induced in the abdominal skin
      of anesthetized rats. Postburn intravenous treatment was given with IP3,
      indomethacin or saline solution. Extravasation of Evans blue albumin in the
      burned tissue was quantified by a spectrophotometric technique. Results showed
      significant inhibition of albumin extravasation by IP3 in three of five different
      doses compared to saline-treated animals. In the second set of experiments, a
      deep full-thickness burn through the abdominal skin and rectus muscle was
      induced. The therapeutic window of IP3 could be more well-defined. Resulted
      showed a significant reduction of albumin extravasation in the skin at all four
      dose levels and in the abdominal muscle at three of four doses. Indomethacin had
      no significant effect on postburn edema formation. The mechanisms responsible for
      the inhibition of albumin leakage by IP3 could be secondary to reduced formation
      of edema-promoting inflammatory mediators by the agent, resulting in improved
      vascular patency.

PMID- 8736366
TI  - Integrin and matrix molecule expression in cultured skin replacements.
AB  - Current tissue culture techniques enable human keratinocytes (HK) from a small
      section of skin to be grown into sheets of epithelium for treating extensive
      wounds. The additional use of dermal replacements coupled with cultured skin
      substitutes may improve handling properties and effect ultimate healing results.
      Adhesion of cultured HK grafts to wounds, and final success rates of HK grafting,
      are variable and frequently unsatisfactory. To evaluate adhesion molecule
      (integrin) expression by cultured grafts, as well as matrix molecule
      distribution, we performed immunohistologic analysis of integrin expression on HK
      cultured on plastic and a polyurethane membrane, as well as on two dermal
      substitutes. Multilayered HK sheet grafts were prepared by culturing cells in
      plastic tissue culture dishes, and HK were cultured to single-layer confluence on
      polyurethane membranes (Hydroderm; Wilshire Medical Inc., Dallas, Texas).
      Composite grafts were prepared by seeding proliferating HK on Dermagraft,
      composed of human neonatal fibroblasts cultured in polyglactin mesh (Advanced
      Tissue Sciences, La Jolla, Calif.) and on AlloDerm, an acellular human dermis
      (LifeCell Inc., The Woodlands, Texas). Immunohistologic staining was performed
      for the integrin subunits alpha 5, alpha 6, and alpha v. Staining for matrix
      molecules included fibronectin, laminin-1, and laminin-5. HK in cultured
      epithelial sheets showed integrin alpha 6 expression on basal cells, and only
      faint alpha 5 and alpha v staining. HK cultured to confluence on Hydroderm
      reacted with monoclonal antibodies specific for alpha 5, alpha 6, and alpha v.
      Through HK adhered well to Dermagraft, there was reduced adhesion of HK on
      AlloDerm that was not accelerated by addition of fibronectin. HK in composite
      grafts showed distinct reactivity according to the time in culture. HK on
      Dermagraft lost alpha 5 reactivity by day 17 and only weak alpha v reactivity was
      seen. Basal keratinocytes on AlloDerm, however, remained alpha 5 and alpha v
      positive. In both composite grafts, integrin alpha 6 expression was limited to
      basal keratinocytes.

PMID- 8736367
TI  - Prognostic indicators in the elderly patient with burns.
AB  - Elderly patients with burns present unique challenges to the burn team. The
      present study was designed to evaluate the impact of specific preinjury health
      conditions, mechanisms of injury, and postinjury complications on their survival.
      A retrospective review of 252 patients more than 55 years of age evaluated
      demographic information, premorbid medical conditions, burn characteristics,
      clinical management, complications, and survival during a 12-year period. For
      comparison, these individuals were divided into four age groups: I (55 to 65), II
      (66 to 75), III (76 to 85), and IV (86 to 96). Although burn size did not change
      with age, patients more than 75 years of age experienced a significantly higher
      mortality rate (60.1%, groups III, IV vs 33.9%, groups I, II, p < 0.05).
      Preinjury health problems were observed in more than two thirds of the patients,
      and when two or more were present, there was a higher incidence of complications
      (65.4% vs 45.3%, p < 0.05) and death (53.0% vs 33.5%, p < 0.01). The effect of
      premorbid health problems on outcome was most evident in the youngest age group.
      Prolonged hospital stays and lower survival rates were observed when more than
      one complication occurred during hospitalization (1 complication, 60.8% survival;
      2 or more, 28.0%, p < 0.001). Older age groups more commonly had infections (IV,
      76.2%) and a fatal outcome when systemic sepsis occurred (IV, 100%). The lower
      respiratory tract was the most common site of infection (24.6%) and carried the
      highest incidence of sepsis (15.1%) and death (13.1%). Certain predictors of poor
      outcome have been identified in elderly patients with burns, which will aid our
      treatment of this patient population and facilitate family counselling.

PMID- 8736368
TI  - Differences in IgM synthesis to gut bacterial peptidoglycan polysaccharide after
      burn injury and gut ischemia.
AB  - Both burn injury and intestinal ischemia have been proven to induce bacterial
      translocation from the gut. It is still unknown, however, whether the bacteria
      induces immune response in these different models. To assess this, we measured in
      vitro IgM synthesis to peptidoglycan polysaccharide (PGPS), a ubiquitous gut
      bacterial antigen, after burn injury or gut ischemia-reperfusion in a mouse
      model. Eighty-five BALB/c mice were divided into four groups. Gut ischemia was
      produced by placing a vessel loop around the superior mesenteric artery at
      celiotomy (group Isc; n = 31). After 45 minutes, the abdomen was reopened, and
      the vessel loop removed. All animals had visible gut ischemia. Control mice
      (group Isc-C; n = 15) underwent two sham operations. Burn injury was 25% body
      surface area full-thickness to the dorsum (group B; n = 27). Another control
      group (B-C; n = 12) was also used. Animals were euthanized 24 hours after
      recirculation or 5 days after the burn injury. All spleens were removed, and cell
      suspensions prepared. Cells were cultured in 2.5 micrograms/ml lipopolysaccharide
      for 5 days, and anti-PGPS IgM level in the supernatant was measured by an enzyme
      linked immunosorbent assay. Intestinal ischemia produced a significant rise in in
      vitro anti-PGPS IgM synthesis per 10(5) lymphocytes, which is the principal
      immunoglobulin response to infection. However, anti-PGPS IgM in mice after burn
      injury was significantly decreased. This decreased IgM synthesis after burn
      injury compared to gut ischemia may represent continued immune impairment from
      the burn wound, and may account for organ dysfunction related to bacterial
      translocation after burn injury.

PMID- 8736369
TI  - Acute and chronic respiratory complications of toxic epidermal necrolysis.
AB  - Toxic epidermal necrolysis (TEN) is a rare disease resulting in bullous necrosis
      of the epidermis with partial-thickness loss of skin and mucous membranes.
      Previous reports of TEN have not focused on respiratory complications. During a 6
      year period, 12 patients with biopsy-proven TEN were referred to a regional burn
      unit at the Wellesley Hospital, Toronto. Five patients required mechanical
      ventilatory support, and nine showed roentgenographic evidence of respiratory
      complications that had developed. Intensive therapy in a critical care burn unit
      resulted in a 75% survival rate. The four nonsurvivors had severe preexisting
      multisystem disease. Four survivors were observed prospectively, with 3 monthly
      pulmonary function testings performed. The four survivors tested, even if they
      did not require mechanical ventilatory support, showed evidence of respiratory
      involvement. Three patients demonstrated a persistent reduction in carbon
      monoxide diffusing capacity of up to 35% to 40% below normal. From our case
      series we suggest that TEN, although primarily a dermatologic condition, may
      result in life-threatening acute respiratory decompensation requiring ventilatory
      support and long-term pulmonary function abnormalities. Patients with TEN should
      be closely monitored for pulmonary complications.

PMID- 8736370
TI  - Formic acid inhalation injury: a case report.
AB  - We report a case in which a patient sustained an inhalation injury as a result of
      aerosolized formic acid. The patient sustained a partial-thickness burn to the
      face from a chemical spray; however, as a result of aerosolization, he also
      inhaled formic acid. This resulted in a reversible pulmonary chemical injury.
      Inhalation of formic acid results in a reactive airway dysfunction syndrome--a
      common response to inhalation of an occupational irritant.

PMID- 8736371
TI  - Intradermal injection of epinephrine to decrease blood loss during split
      thickness skin grafting.
AB  - After a burn injury, the hemodynamics of a patient is changed. There is usually a
      fall in hematocrit. In addition to this, there is the loss of blood during the
      grafting procedure. Some patients cannot tolerate this loss of blood. The method
      we use to help decrease the loss of blood during skin grafting is an injection of
      epinephrine intradermally before the graft and eschar are excised. We have found
      this method to be useful in a select group of patients.

PMID- 8736372
TI  - Dermasorb versus Jelonet in patients with burns skin graft donor sites.
AB  - A prospective and randomized trial that compares Jelonet (Smith & Nephew PLC,
      London, England) with a new hydrocolloid dressing, Dermasorb (Convatec Ltd.,
      Clwyd, United Kingdom), is presented. The dressings were applied on contiguous
      donor sites in 21 patients that required skin grafting for burn wounds. Pain
      experienced with the dressing in situ was assessed on days 2, 4, 7, and on two
      subsequent occasions. During dressing changes, pain experienced was again
      assessed, bacteriologic swabs were taken, and the percentage of epithelialization
      was recorded. Questionnaires completed by investigators and patients were used to
      assess the perceived performances of both dressings. The results showed that
      Dermasorb is a less painful dressing than Jelonet, in which wounds heal faster.
      Dermasorb was preferred by both investigators and patients. No clinical or
      laboratory evidence of any differences of colonization or infection were found.
      All results were statistically significant. We would strongly recommend the use
      of Dermasorb as a split-thickness skin graft donor site dressing for a patient
      with burns.

PMID- 8736373
TI  - The effects of soft tissue mobilization on the immature burn scar: results of a
      pilot study.
AB  - The purpose of this pilot study was determine the effects of soft tissue
      mobilization (STM) on range of motion (ROM), scar pliability, and vascularity.
      Patients received either one treatment session of standard physical therapy or
      standard physical therapy plus 10 to 15 minutes of STM. Before and after ROM,
      scar pliability and vascularity measurements were obtained. The student's t test
      was used to compare measurements and revealed the STM group (n = 5) had
      significant (p < 0.10) gains in wrist extension and radial deviation, and the
      control group (n = 5) had significant gains in wrist extension and ulnar
      deviation. No significant difference was found in ROM, scar pliability, and
      vascularity when the STM group was compared to the control group. Further study
      of a larger sample over multiple treatment sessions is necessary to determine the
      true efficacy of STM.

PMID- 8736374
TI  - Animal extremists: a cause for concern?
AB  - Investigators in various biomedical specialties, as well as hunters, farmers, and
      fur ranchers, have been victimized by animal rights extremists in the United
      States, the United Kingdom, and other countries during recent years. Given the
      extent of animal-based burn research, in which rodents and higher mammals are
      subjected to burn and smoke trauma, the potential for a liberation attack by an
      animal rights fringe group must be taken seriously. Suggestions are given to
      researchers and their institutions to prevent or minimize such an attack.

PMID- 8736375
TI  - Essential microminerals and their response to burn injury.
AB  - Certain microminerals, named because of their minute quantities in the body, are
      essential components for maintaining homeostasis involving, in particular,
      metabolism, immune defense, and wound healing. In general, these trace elements
      are characterized by having multiple roles and by demonstrating deficiency
      syndromes that are complex and difficult to diagnosis. The response of the
      microminerals to injury, especially burn injury, is not well defined. The purpose
      of this article is to describe the known roles of the trace elements and the
      effect of burn injury on circulating and tissue levels. As will be noted, much
      less is known regarding the impact of trace elements' changes on the injury
      process than the role of these elements in the normal state. In addition, the
      amount of trace elements needed for the stress changes after injury are, for the
      most part, undefined.

PMID- 8736376
TI  - Propane gas dangers and strategies for prevention of injuries.
AB  - Although the overall incidence of thermal injuries continues to decrease, the
      incidence of certain types of burns is alarmingly high. Approximately 3000
      propane fires and explosions are reported yearly. More than 9% of these cases
      result in bodily injury, and the mortality rate is more than 7% of the injured.
      Most of the accidents are felt to be the result of a lack of knowledge among the
      general public in regard to the use of liquid petroleum (LP) gas, which is a low
      cost and widely used fuel source. A series of accidents that resulted in several
      injuries in the midsouth area heightened our awareness of the problems associated
      with LP-gas storage, transportation, and use. A review of the incidence of use
      and injury, warning systems, product liability status, and prevention strategies
      are reported to help educate health care providers and increase public awareness
      of the problems associated with propane gas.

PMID- 8736377
TI  - Results of a hospital survey to determine the extent and type of psychologic
      services offered to patients with severe burns.
AB  - Surveys sent to psychologic service providers at the 159 burn care hospitals in
      the United States and Canada elicited 69 responses with 66 completed forms.
      Results indicated that few hospitals provide formal psychologic testing for their
      patients who require acute or reconstructive care. However, respondents estimated
      that more patients display symptoms of depression and post-traumatic stress
      disorder than are given counseling or psychologic therapy. Referrals for
      counseling or therapy at discharge and appointments for follow-up visits to
      assess emotional health are given to approximately two thirds of the patients. A
      disturbing survey finding was that many respondents reported that their hospital
      staff, 6 months after beginning to work on the unit, also displays symptoms of
      depression and post-traumatic stress disorder.

PMID- 8736378
TI  - Stabilization of endotracheal tubes in children.

PMID- 8736379
TI  - Clarification on the use of silver-based purification systems.

PMID- 8736380
TI  - Anesthesia and thermal injury.

PMID- 8736381
TI  - Hepatotumorigenicity and peroxisome proliferation induced by the hypolipidemic CI
      924 in a two-year study in male and female B6C3F1 mice.
AB  - The hepatic tumorigenicity of CI-924 (5,5'-(1,1'-biphenyl)-2,5-diylbis(oxy)(2,2
      dimethylpentanoic acid)), a hypolipidemic agent, was evaluated in 50 B6C3F1
      mice/sex/dose given drug in the diet at 0, 5, 25, and 75 mg/kg/day for 2 yr.
      Peroxisomal and drugmetabolizing enzyme determinations, as well as
      ultrastructural evaluations, were conducted in subsets of these same groups,
      because drugs of this class cause peroxisome proliferation and hepatic tumors in
      rodents. CI-924 elicited dose-dependent increases in the incidence of
      hepatocellular adenomas and carcinomas in both sexes that were statistically
      significant at 75 mg/kg. Stereologic evaluation revealed significant increases in
      hepatocellular peroxisome volume ratio, due to increased numbers of peroxisomes,
      in females at all doses and males at 75 mg/kg. Peroxisomal enzyme activity
      measurements revealed no change in catalase, but dose-dependent increases in
      carnitine acetyltransferase and cyanide-insensitive beta-oxidation in both sexes.
      Peroxisome proliferation, determined biochemically or ultrastructurally, was
      twice as great in females compared to males. Total cytochrome P-450 was increased
      in both sexes given 75 mg/kg. There were dose-dependent decreases in glutathione
      S-transferase in males and increased glutathione peroxidase in both sexes at 25
      and 75 mg/kg. In conclusion, this study demonstrated that while CI-924 induced
      hepatic tumors in male and female B6C3F1 mice the associated peroxisome
      proliferation, while moderate in females, was only weak in the males after 2 yr
      of exposure.

PMID- 8736382
TI  - Chronic administration of the mutagenic heterocyclic amine 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine induces cardiac damage with characteristic
      mitochondrial changes in Fischer rats.
AB  - Fischer-344 rats of both sexes were administered the heterocyclic amine 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) for 52 wk at the dietary level of
      400 ppm. Light microscopic and ultrastructural investigation of the myocardium
      revealed prominent changes in all PhIP-treated male and female animals
      investigated. These were characterized by a diffuse proliferation of markedly
      enlarged mitochondria, with abundant cristae and often containing lamellar bodies
      as inclusions. PhIP is well known to cause DNA adducts in the rat heart, and
      there are numerous reports of mutations in mitochondrial DNA in both humans and
      experimental animals being associated with very similar lesions to those observed
      in the present study. The results thus suggest that this heterocyclic amine
      induces cardiac damage by the same mechanism.

PMID- 8736383
TI  - Regulatory issues of importance to developing anti-HIV therapeutics.
AB  - In the United States, before clinical trials with new drugs can proceed, an
      Investigational New Drug (IND) application must be submitted to the Food and Drug
      Administration. Applications for drugs intended for the treatment of HIV-related
      diseases are reviewed by the Division of Anti-Viral Drug Products (DAVDP) within
      the Center for Drug Evaluation and Research. IND applications must contain
      adequate preclinical studies to support the safety of the proposed clinical
      trials. Essential for demonstrating safety are animal toxicology studies in which
      the drug has been administered in doses, by the route(s) of administration, and
      over a length of time equivalent to the corresponding parameters proposed for
      clinical trials. Reproductive toxicology/teratology studies should be conducted
      early in the development of the drug. Other nonclinical toxicology studies, such
      as carcinogenicity bioassays, are usually conducted concurrently with clinical
      trials. The DAVDP has developed a Pre-IND program to assist sponsors in preparing
      the best preclinical research to support the development of new drugs.

PMID- 8736384
TI  - Hepatic neoplasms from internally deposited 144CeCl3.
AB  - Fifty-five dogs were exposed by inhalation to graded activity levels of 144CeCl3,
      a relatively soluble form of the beta-emitting radionuclide. A large portion of
      the 144Ce translocated from lung to liver and skeleton. Significant radiation
      doses were delivered to the respiratory tract, liver, and skeleton; however, the
      liver received the greatest cumulative absorbed dose. Liver tumors were the most
      frequently observed neoplasms in these exposed dogs and included 7 primary
      hepatic hemangiosarcomas, 1 cholangiocarcinoma, 1 hepatocellular carcinoma, 1
      fibrosarcoma, 4 biliary cystadenomas, and 1 fibroma. The dose to the liver in
      these dogs ranged from 11 to 250 Gy with a median of 57 Gy. Autoradiographs
      showed a relative uniform distribution of beta dose to the liver. All the
      malignant tumors and 1 cystadenoma were primary causes of death. The morphologic
      features of the hemangiosarcomas and associated hepatic lesions were similar to
      those described for hemangiosarcomas induced in people exposed to Thorotrast.
      Biliary cystadenomas were associated with degenerative lesions in the liver but
      not with other neoplasms in the liver. These results indicate that the liver is
      an important target organ for effects from internally deposited 144Ce.

PMID- 8736385
TI  - Integrated evaluation of central nervous system lesions: stains for neurons,
      astrocytes, and microglia reveal the spatial and temporal features of MK-801
      induced neuronal necrosis in the rat cerebral cortex.
AB  - Routinely processed, hematoxylin and eosin (H&E)-stained slides are typically
      used to assess the morphologic integrity of the central nervous system in
      neurotoxicity safety studies. However, the value of special stains for improving
      neuropathologic evaluations during the assessment of neurotoxicity has been
      emphasized in the neuroscience literature and by regulatory agencies. The primary
      objective of the present study was to characterize the spatial and temporal
      changes in neurons, astrocytes, and microglia after dizocilpine maleate (MK-801)
      induced focal neuronal necrosis in the posterior cingulate/retrosplenial (PC/RS)
      cortex of the rat. A secondary objective was to evaluate the application of
      special stains and a novel sectioning procedure for detecting neurotoxicity.
      Sixty adult male Sprague-Dawley rats were treated with sterile water vehicle or
      10 mg/kg MK-801 and perfused through the left ventricle (pumped at 65 mm Hg
      pressure) with 10% neutral buffered formalin or 4% paraformaldehyde at 4 hr and
      on days 1, 3, 7, 14, and 28 after treatment. For light microscopic evaluation,
      brain sections were stained with H&E, a special cupric-silver (CS) stain that
      selectively impregnates degenerating neurons and makes them readily evident,
      glial fibrillary acidic protein (GFAP) immunohistochemistry for astrocytes, and
      Griffonia simplicifolia isolectin B4(GSA) histochemistry for microglia. Brains
      perfusion-fixed with 4% paraformaldehyde were prepared for CS staining with a
      novel frozen-sectioning procedure for multiple embedding in a composite gelatin
      block. In H&E sections from treated rats, necrotic nerve cell bodies were
      observed in PC/RS cortical layers 3 and 4 on days 1, 3, 7, and 14, but not on day
      28. These necrotic neurons required high magnification for detection (x20
      objective, x10 ocular). In contrast, degenerating neurons selectively stained
      with CS were observed in the same location as necrotic neurons seen with H&E but
      at low magnification (x2 objective, x10 ocular). Cupric-silver staining showed
      details not seen with H&E, including dendritic and axonal degeneration with
      progressive fragmentation. Beginning on day 3, GFAP immunohistochemistry revealed
      hypertrophic astrocytes in a diffuse pattern throughout the region of cell body
      necrosis, a change that persisted throughout the study. However, GSA lectin
      histochemistry identified a few reactive microglia on day 1 in a multifocal
      pattern throughout the region of cell body necrosis. Reactive microglia were
      observed on days 3, 7, and 14, but not on day 28. Glial changes observed with H&E
      staining were limited to an increase in the cellularity of glial cell nuclei in
      the area of neuronal necrosis. This study provides a comprehensive and integrated
      view of the temporal changes occurring in neurons, astrocytes, and microglia
      during acute neurotoxic injury. Moreover, advantages for using new staining and
      sectioning methodologies to enhance the toxicologic evaluation of the central
      nervous system are demonstrated.

PMID- 8736386
TI  - The interactions of diet and colonic microflora in regulating colonic mucosal
      growth.
AB  - The colonic mucosa can adapt its growth to alterations in diet. Metabolites from
      colonic microflora are frequently implicated as the primary factor in mediating
      the colonic mucosal response to diet; however, there is also evidence indicating
      that diet may have a direct effect in mediating this response. The aim of this
      study was to determine the role of diet, microflora, and microflora metabolites
      in altering the growth of the colonic mucosa. Two 28-day feeding studies were
      conducted using Sprague-Dawley rats. The first study compared the growth of the
      colonic mucosa in germ-free and conventional rats fed 6 different diets. The
      second study compared the growth of the colonic mucosa to the concentration of
      bacterial-derived short-chain fatty acids (SCFs), bile acids, and ammonia. The
      diets that were fed consisted of (1) AIN-76a diet without dietary fiber; (2)
      standard AIN-76a diet, which contained 5% cellulose; (3) AIN-76a diet with 5%
      guar gum; (4) a "Western" human diet with 20% fat and 10% cellulose; (5) AIN-76a
      diet formulated to mimic Diet 4 in fat content but with 2.5% cellulose; and (6)
      Purina Rodent Chow. Quantitative volumetric and stereologic analysis was used to
      assess changes in total colonic mucosal volume as a measure of mucosal growth. In
      germ-free rats, Diets 2-4 and 6 induced a significant increase (18-38%) in
      mucosal volume compared to Diet 1. In conventional animals, only Diets 4 and 6
      induced a significant increase (up to 63%) in mucosal volume compared to Diet 1.
      Relative to the germ-free animals, only conventional animals on Diets 4 and 6 had
      an increase in mucosal volume. The increases in mucosal volume in Diets 4 and 6
      were not consistently associated with increased SCFAs, ammonia, or bile acids.
      There was a wide range in the colonic concentrations of SCFAs (2-fold), ammonia
      (6-fold), and bile acids (10-fold). The presence of colonic microflora in and of
      itself does not lead to enhanced colonic mucosal growth. Rather, there are unique
      interactions between specific types of diet and microflora that lead to a growth
      promoting effect. This effect could not be explained by alterations in the
      concentration of SCFAs, ammonia, or bile acids in colonic contents.

PMID- 8736387
TI  - 1995 STP Young Investigator Award recipient. Increased rate of apoptosis
      correlates with hepatocellular proliferation in Fischer-344 rats following long
      term exposure to a mixture of groundwater contaminants.
AB  - Apoptosis was evaluated in the livers of Fischer-344 rats following observations
      of increased hepatocellular proliferation from exposures, at low parts per
      million (ppm) levels, to a drinking water mixture of 7 groundwater contaminants
      during a 6-mo time-course study. The 7 chemicals used are among the most
      frequently detected contaminants associated with hazardous waste sites: arsenic,
      benzene, chloroform, chromium, lead, phenol, and trichloroethylene. Significant
      increases in 5-bromo-2'-deoxyuridine hepatocellular labeling were present in a
      unique pattern surrounding large hepatic veins (0.5-2.0 mm). This did not appear
      to be a regenerative response due to cytotoxicity, as assessed by the absence of
      increased plasma enzyme activity and the absence of hepatocellular lesions.
      Immunohistochemical staining for apoptosis, using the terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end labeling (TUNEL) method showed patterns
      of labeling in treated animals that directly correlated to areas of increased
      hepatocyte proliferation. Apoptotic activity was maximum at the 1-mo exposure
      time point, whereas proliferating hepatocytes reached a maximum rate at the 10
      day time point. This may have been triggered as a compensatory response to the
      increased cell proliferation or as a protective response to remove cells with
      altered DNA due to chemical mixture exposure. The principal findings of this
      paper are that (a) apoptosis directly correlated with changes in cell
      proliferation: (b) observed effects were produced by repeated exposures to a
      relatively low-level chemical mixture; and (c) the TUNEL method detected
      apoptotic cells at very early and late stages, potentially increasing the
      observable time period for apoptosis.

PMID- 8736388
TI  - N-methyl-N'-nitro-N-nitrosoguanidine-induced neoplasms in medaka (Oryzias
      latipes).
AB  - To test the sensitivity of the small fish species Oryzias latipes to the direct
      acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), medaka were
      exposed at 15 days of age to 30 mg/L for 1 hr and followed for up to 16 mo. One
      hundred neoplasms were diagnosed in 84 of 213 exposed fish, with approximately
      equal percentages in males and females. Many neoplasms (62%) were of mesenchymal
      origin and were categorized as blood vascular neoplasms (hemangioma and
      hemangiosarcoma), invasive sarcomas, and scale-associated neoplasms. Invasive
      sarcomas included rhabdomyosarcoma, fascial sarcoma, hemangiopericytoma, and
      undifferentiated sarcoma. A scale-associated neoplasm, termed lepidocytoma, was
      an unusual neoplasm of scale anlage. Thyroid follicular neoplasms, with a 100%
      incidence in males, and pancreatic acinar carcinoma were the most common
      epithelial tumors. Neoplasms of the gills, swim bladder, and olfactory epithelium
      were also seen as well as teratoma with mixed epithelial and mesenchymal
      components. The study showed a broad range of neoplasms induced by MNNG in
      medaka, with a tissue distribution that might support direct action on exposed
      tissues.

PMID- 8736389
TI  - Reactivity of tissue-specific antigens in N-methyl-N'-nitro-N-nitrosoguanidine
      induced neoplasms and normal tissues from medaka (Oryzias latipes).
AB  - To further characterize the distribution of tissue-specific antigens in fish
      neoplasms, juvenile medaka were exposed to 30 mg/L of N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) for 1 hr and allowed to grow out for up to 16 mo. Using a
      streptavidin peroxidase technique, keratin, vimentin, and neurofilament
      intermediate filament proteins, and actin and S-100 proteins were labeled in MNNG
      induced neoplasms and normal medaka tissues using specific monoclonal or
      polyclonal antibodies. In vascular tumors, rhabdomyosarcoma, and teratoma, muscle
      tissues were positive for actin. Other sarcomas including hemangiopericytoma,
      fascial sarcoma, and undifferentiated sarcoma were negative for all antibodies
      tested. An unusual scale-associated neoplasm, composed of clusters of scale
      forming cells surrounding spicules of scale, had keratin-positive stroma. The
      epithelial neoplasms were also positive for keratin, except for pancreatic acinar
      carcinoma, which had limited positivity. Both teratoma and olfactory carcinoma
      had S-100-positive intraepithelial cells morphologically reminiscent of
      neurosensory epithelial cells, which were S-100 positive in normal tissues.
      Although positive reactivity in fish tissues correlated with mammalian data, the
      antibodies used were raised against mammalian antigens. Therefore, a negative
      reaction may be indicative of lack of antibody sensitivity to specific fish
      antigens rather than absence of the antigen in the tissues. However, these data
      show that tissue-specific antigen detection may assist in elucidating the biology
      of neoplasia in fish.

PMID- 8736390
TI  - Confocal laser scanning microscopy of oncogene localization in rainbow trout cell
      lines derived from normal and tumor tissue.
AB  - We examined the localization and expression of the nuclear oncoprotein c-myc and
      the cytoplasmic membrane-associated oncoprotein c-ras in rainbow trout cell lines
      derived from both normal and tumor tissue in order to question whether c-myc and
      ras oncoprotein immunostaining was increased in cells derived from tumors
      compared to cells derived from normal tissue. Cell lines examined were derived
      from normal rainbow trout gonadal cells (RTG-2), a rainbow trout hepatoma (RTH
      149), and a rainbow trout mesothelioma (RTM). Protein products of c-ras and c-myc
      were visualized in these 3 cell lines by employing fluorescein-labeled anti-mouse
      pan-ras and c-myc antibodies. The RTG-2 cells were used in this study as normal,
      control cells, and they exhibited little pan-ras and c-myc staining. The RTH-149
      cell line (a tumorigenic cell line) exhibited positive pan-ras staining in
      regions of the membrane and cell cytoplasm. Localization of c-myc staining to
      perinuclear regions was punctate in RTH-149 cells. RTM cells (also a tumorigenic
      cell line) displayed a ras staining localization similar to the pattern seen in
      RTH-149 cells. RTM cells exhibit a diffuse perinuclear staining and, thus,
      display a more ubiquitous localization of c-myc than RTH-149 cells. Northern blot
      analysis indicated that c-myc expression was highest in RTM cells, whereas RTG-2
      cells and RTH-149 cells expressed similar lower levels of c-myc expression. We
      were unable to detect significant ras expression in any of the cell lines by
      Northern blot analysis. In summary, the cell line derived from normal tissue, the
      RTG-2 cells, displayed little ras and c-myc immunostaining, whereas the cell
      lines derived from tumorigenic tissue, RTH and RTM cells, displayed increased
      immunostaining for c-myc and ras proteins.

PMID- 8736391
TI  - Review article. The rat incisor in toxicologic pathology.
AB  - Microscopic examination of the incisors of rats and mice may reveal
      toxicologically significant changes. First, the incisor morphology reflects the
      nutritional status of the animal: fluctuations of mineral metabolism and vitamin
      availability are disclosed by the rodent incisors, because the incisors continue
      to grow during life. Similarly, direct or indirect changes of mineral metabolism
      by a test substance are reflected in the morphological appearance of the incisor
      dentin. In addition, hormonal disturbances may give rise to typical structural
      alterations of the incisor in the test animal. Certain chemicals may have
      deleterious effects upon the odontogenic tissues, resulting in tooth malformation
      and malocclusion and eventually in odontomas. Apparent nasal tumors may turn out
      to be of dental origin. Nasal luminal masses that are discussed within this scope
      are dental malformation, dental callus, and true odontogenic tumors. According to
      our experience, odontogenic tumors might possibly develop within the scope of a
      reaction to mechanical tooth trauma as well. In carcinogenicity studies, this
      consideration deserves attention when evaluating treatment-related putative
      odontogenic tumors.

PMID- 8736392
TI  - Olfactory undifferentiated carcinoma with endocranial extension in a Fischer-344
      rat.
AB  - A spontaneous tumor in the nasal cavity, extending through the cribriform plate
      to the cranial cavity, was detected in a 103-wk-old female Fischer-344/DuCrj rat.
      The tumor appeared to arise from the olfactory epithelium and was composed of
      round to polygonal, undifferentiated cells arranged in solid sheet-like and
      lobular patterns with scant fibrovascular stroma. Ultrastructurally, the tumor
      cells often formed desmosomes between contiguous cells and had no neurosecretory
      granules. Immunohistochemically, the tumor cells did not react with any
      antibodies specific for intermediate filaments, neuronal, muscular, and
      endothelial elements. Based on these results, the tumor was diagnosed as
      undifferentiated olfactory epithelial carcinoma.

PMID- 8736393
TI  - Brief communication, Histopathology of a spontaneously developing mast cell
      sarcoma in a Wistar rat.
AB  - A case report is given of a very rare spontaneous mast cell tumor in the eyelid
      of the left eye of a female Wistar rat used in a long-term oral toxicity study.
      Metastasis of the tumor had occurred in the mandibular lymph nodes and in the
      liver. Clinically, the animal showed blepharospasm, dacryorrhoea, and
      exophthalmus. Hematologic findings included slight eosinophilia and a remarkable
      basophilia. At necropsy, a bilateral conjunctivitis was diagnosed and a tumorous
      mass was found in the left submandibular region. Histologically, the tumor was
      composed of round to polygonal cells with pale cytoplasm, containing abundant
      predominantly basophilic granules. The intracytoplasmatic granules stained
      metachromatically with Toluidine blue and immunostained positively with
      serotonin. Numerous eosinophils were scattered throughout the tumor and were also
      present in other organs. Cells with round, oval, or indented nuclei and abundant
      cytoplasm, containing pronounced eosinophilic granules, were found in spleen and
      bone marrow. They turned out to be immature stages of eosinophilic granulocytes.
      Characteristics of the present tumor are compared with observations on mast cell
      tumors in other species.

PMID- 8736394
TI  - Brief communication, P53 accumulation in N-methyl-N-nitrosourea-induced rat
      mammary tumors.
AB  - P53 aberrant protein expression and mutation is a component of many human tumors
      but less information is available regarding involvement in relevant animal
      models. We have examined invasive mammary epithelial neoplasms for p53 aberrant
      protein expression from Sprague-Dawley rats induced by two intrajugular
      injections of N-methyl-N-nitrosourea (NMU, 50 mg/kg), 7 days apart, beginning at
      44-49 days of age. Positive nuclear staining was observed in 8/10 mammary tumor
      frozen sections using PAb 421, a mouse monoclonal antibody, compared to a mixed
      mouse IgG negative control antibody. Paraffin sections from two additional sets
      of similarly induced rat mammary tumors also showed positive nuclear staining
      (22/37 tumors) with CM-5, a rabbit polyclonal antibody. Our results indicate that
      elevated cellular content of p53 is a common event in invasive palpable mammary
      tumors induced by NMU in this dual-injection model system.

PMID- 8736395
TI  - Commentary. The uncontrolled variable in risk assessment: ad libitum overfed
      rodents--fat, facts and fiction.

PMID- 8736396
TI  - Neurotoxicity: a field of increasing importance for the toxicologic pathologist.

PMID- 8736400
TI  - Personal reminiscences: the development of neurology at the Montreal Children's
      Hospital.

PMID- 8736401
TI  - Evoked potentials as predictors of outcome in neonatal intensive care unit
      survivors: review of the literature.
AB  - Neonatal intensive care unit survivors are at substantial risk for a range of
      neurodevelopmental sequelae, and therefore a variety of clinical diagnostic
      techniques have been evaluated as predictors of outcome. We summarize the
      prognostic value of evoked potentials in newborns at risk. A review of the
      literature reveals that brainstem conduction abnormalities in auditory brainstem
      evoked potentials are associated with neuromotor impairment; however, there are
      many false negative studies. Visual evoked potentials are highly accurate in
      predicting neurologic deficits in early childhood in asphyxiated term neonates.
      Sensitivity and specificity are consistently high for somatosensory evoked
      potentials in term newborns; however, correlations with outcome in premature
      infants is controversial. Several studies have compared neonatal findings on
      neuroimaging studies and evoked potentials, and concordant results between these
      two tests are highly predictive. However, neurologic sequelae often can most
      accurately be predicted by visual or somatosensory evoked potentials. Evoked
      potentials may therefore be a useful adjunct to the clinical investigation and
      prognostication of outcome in the high risk newborn.

PMID- 8736402
TI  - Differential diagnosis of staring spells in children: a video-EEG study.
AB  - Staring is frequently a nonepileptic manifestation in children. To differentiate
      epileptic versus nonepileptic staring, we reviewed clinical and video-EEG
      findings in 143 patients, aged 5 months to 43 years, monitored for staring
      episodes. In 79 patients staring was of epileptic origin; 46 had partial seizures
      and 33 atypical absence. Thirty-five had behavioral staring, 8 psychogenic
      seizures, 1 a migraine equivalent, and in 20 no staring spells were recorded. In
      all patients with epileptic staring, epilepsy was suspected clinically. Only 22
      of the admissions for behavioral staring and 3 for pseudoseizures were to exclude
      a possible nonepileptic phenomenon. Review of their clinical histories revealed
      that certain findings strongly support a nonepileptic origin. In conclusion, a
      careful clinical history will differentiate between epileptic and nonepileptic
      staring episodes in most patients. Video-monitoring is helpful to adjust
      treatment or to exclude nonepileptic events in patients with refractory staring
      spells.

PMID- 8736403
TI  - Mitochondrial DNA depletion: prevalence in a pediatric population referred for
      neurologic evaluation.
AB  - Mitochondrial DNA depletion is a quantitative disorder of mtDNA, characterized by
      tissue-specific reductions in mtDNA copy number, that presents in infancy or
      early childhood. It is most likely transmitted as an autosomal recessive trait,
      although about half of the described cases are sporadic. To estimate its
      prevalence we measured relative mtDNA copy number (mtDNA: 18S rDNA ratio) by
      Southern blot analysis in muscle biopsy samples from all children with compatible
      histories referred between 1983 and 1994. Of the 304 biopsies evaluated, 54 met
      the study criteria. We found 6 patients (2 male, 4 female) with mtDNA depletion
      (relative mtDNA copy number 7.9-33.2% of control). Their clinical course and
      findings were heterogeneous, however all but one manifested weakness, hypotonia,
      and developmental delay. Clinical severity was not obviously related to the
      degree of mtDNA depletion. No patient had ragged-red fibers, although 2 had a
      lipid storage myopathy. Immunofluorescence with antibodies to double-stranded
      DNA, COX IV, and COX II demonstrated homogeneously reduced reactivity to all
      three antibodies compared with control. mtDNA depletion may be a relatively
      common neurogenetic disorder of infancy and early childhood and should be
      considered in children with unexplained weakness, hypotonia, or developmental
      delay.

PMID- 8736404
TI  - Acephalgic migraines of childhood.
AB  - Migraine aura without headache (acephalgic migraines) is a recognized subset of
      migrainous phenomena in the adult population. No reports of its prevalence or
      characteristics in a series of children exists. Using diagnostic criteria for
      migraine aura without headache established by the International Headache Society,
      a retrospective review of a computerized database of all patients referred over a
      4-year period (July 1991 to June 1995 inclusive) to a single university-based
      pediatric neurologist was performed. Fourteen patients were identified,
      representing 2% of all patients with a primary diagnosis of migraine. Nine were
      females and 13 had a strong family history of migraines. Age of onset of symptoms
      ranged from 5 to 12 years with a mean of 8 years. Symptoms were episodic in all,
      varying in frequency from weekly to more typically monthly, lasting generally
      less than 10 min. In 9 patients the aura described was that of often colorful
      photopsias or scintillating scotomas. Two had micropsia, one had temporal
      distortion (time "speeded up"), one had hyperacusis, and the final patient had a
      vague sense of disconnection from her surroundings. Only 2 patients had a
      headache occasionally associated with the described aura. In addition to the
      acephalgic migraines, 9 patients had either common or classical migraines, the
      latter typically featuring aura distinct from those observed in these patients'
      acephalgic episodes. Neurologic examination, electrophysiologic investigation
      (EEG/evoked potentials), and neuroimaging were noncontributory in all instances.
      Migraine aura without headache is a recognizable benign migraine syndrome of late
      childhood.

PMID- 8736405
TI  - Deferring adjuvant therapy for totally resected intracranial ependymoma.
AB  - Radical surgery is the most important treatment modality for ependymoma. The
      benefit of adjuvant radiotherapy and/or chemotherapy following a gross total
      resection of a low grade intracranial ependymoma is uncertain. Since 1990 we
      elected to defer adjuvant therapy in 7 pediatric patients with a median age of 7
      years (range 3-16 years) who had a radical resection of an intracranial
      ependymoma and no evidence of central nervous system metastases. The primary
      tumor site was the cerebral hemisphere (6) and the cerebellum (1). A gross total
      resection was radiologically confirmed in 5 of the 7 patients. Two of the
      patients had a blood clot in the resection site on the postoperative magnetic
      resonance imaging scan. All patients are alive after a median follow-up of 44
      months and the median progression-free survival is 38+ months. Five of the
      patients remain in continuous remission. The 2 patients with postoperative blood
      clots developed subclinical local recurrences, 10 and 11 months, respectively,
      after diagnosis. They remain in remission for 13+ and 27+ months after subsequent
      radical surgical procedures. Involved field radiotherapy was administered to 1
      patient. After a limited period of follow-up, radical surgery alone appears to be
      sufficient for the majority of children with low grade ependymomas diagnosed at >
      3 years of age when postoperative imaging confirms a gross total resection. This
      is more likely to occur in supratentorial ependymomas arising in older children.

PMID- 8736406
TI  - Infantile spasms: cerebral blood flow abnormalities correlate with EEG,
      neuroimaging, and pathologic findings.
AB  - This ongoing study examines abnormalities of cerebral perfusion in a consecutive
      series of children with infantile spasms and correlates cerebral blood flow (CBF)
      abnormalities with electroencephalographic (EEG), neuroimaging, and pathologic
      findings. A consecutive series of children with infantile spasms, diagnosed by
      standard clinical and EEG criteria, had cerebral perfusion studies using 99Tc
      HmPAO single photon emission computed tomography (SPECT), together with
      neuroimaging studies using computed tomography (CT) and/or magnetic resonance
      imaging (MRI), interpreted independently and correlated with surgical pathologic
      findings. Twenty children aged 2-13 months (mean 9.3 months) were studied over a
      4-year period; 60% had symptomatic infantile spasms due to cerebral dysgenesis
      (33%), other congenital lesions (25%), tuberous sclerosis (17%), or other causes
      (25%), and the remaining patients were cryptogenic (40%). CBF abnormalities were
      present in 85%: multifocal decrease (40%), focal increase (25%), diffuse decrease
      (15%), and focal increase (10%), while the remaining 15% had normal cerebral
      blood flow. Focal cortical lesions may lead to infantile spasms, even in
      cryptogenic patients diagnosed by functional neuroimaging such as 99Tc-HmPAO
      SPECT. In selected patients, surgical excision of the cortical lesions leads to
      improved seizure control and possibly outcome. The localization and surgical
      excision of focal cortical lesions in infantile spasms required further
      investigation with functional and structural neuroimaging, EEG, and
      intraoperative electrocorticography.

PMID- 8736407
TI  - Encephaloduroarterio-synangiosis in a child with sickle cell anemia and moyamoya
      disease.
AB  - We report a black girl with sickle cell anemia. On prophylactic exchange
      transfusion protocol, she experienced cerebrovascular accidents at 3 and 3.5
      years of age, both associated with transient right hemiparesis. At 7.5 years of
      age, she presented with a partial motor seizure and a left hemiparesis. A
      cerebral angiogram demonstrated stenosis at the origins of both middle and
      anterior cerebral arteries bilaterally with extensive basal collateralization.
      She underwent uncomplicated bilateral encephaloduroarteriosynangiosis (EDAS)
      procedures using both superficial temporal arteries. At age 9 years, the patient
      presented with a severe headache and tunnel vision secondary to a stenosis of
      both posterior cerebral arteries. She underwent bilateral EDAS procedures using
      both occipital arteries. No complication was encountered. Postoperative cerebral
      angiogram demonstrated impressive neovascularity at the sites of all four EDAS
      procedures. Different treatment options of moyamoya disease are discussed.

PMID- 8736408
TI  - Cauda equina histiocytosis X.
AB  - A young child was admitted with a cauda equina syndrome believed to be
      progressive, but unrelated to a congenital anomaly. Magnetic resonance imaging
      studies revealed the presence of an intradural tumor in the cauda equina. A
      yellow pasty tumor with nerve root infiltration was identified at surgery.
      Histologic features were pathognomonic for histiocytosis X. The patient's
      management and review of the literature are discussed.

PMID- 8736409
TI  - The clinical spectrum of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.
AB  - Four patients with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
      are presented. Clinical onset in the form of acute encephalopathy occurred
      between the ages of 9 months and 3 years. The clinical course included recurrent
      metabolic crises in 4 patients, cardiac involvement and retinopathy in 3, and
      myopathy in 2. None had signs of peripheral neuropathy. Three patients died and
      one is currently well. Hypoketotic hypoglycemia with C6-C14 3-hydroxy
      dicarboxylic aciduria during metabolic crises associated with decreased plasma
      carnitine levels was the main biochemical finding. Enzymologic studies disclosed
      long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency in all patients.
      Homozygosity for a G to C mutation at position 1528 in the encoding region of the
      enzyme was found in 2 patients. Histologic and electron microscopic studies of
      liver biopsy specimens revealed steatosis in 3 patients and mitochondrial
      abnormalities in 2. Skeletal muscle biopsies disclosed nonspecific degenerative
      changes in 2 patients and were normal in the remaining 2. Ultrastructural
      abnormalities in mitochondria were found in 3 patients. A review of the
      literature combined with the data from our series (total 22 patients) disclosed
      acute clinical onset in 77% of cases and subacute in 23%. In the combined series,
      the average age at onset was 11 months, family history was positive in 32% of
      patients and overall mortality was 50%. We describe the clinical spectrum of this
      disease and emphasize that, among patients with suspected beta-oxidation defects
      the finding of pigmentary retinopathy should lead to the suspicion of long-chain
      3-hydroxyacyl-coenzyme A-dehydrogenase deficiency.

PMID- 8736410
TI  - Epidemiology of bacterial meningitis in children: Aichi Prefecture, Japan, 1984
      1993.
AB  - The details of 328 patients with bacterial meningitis, admitted from 1984 through
      1993, were obtained from 46 departments of pediatrics of large hospitals through
      questionnaires. The incidence rate per 100,000 child-years was 2.32, being higher
      in children aged 0-4 years (rate, 7.22) than 5-15 years (rate, 0.49). The disease
      in the 274 (84%) etiologically diagnosed patients was due to Haemophilus
      influenzae (95), Streptococcus pneumoniae (56), Group B streptococci (GBS) (41),
      Escherichia coli (27), and other agents (55), including 7 patients with
      Mycobacterium tuberculosis infection. The short-term outcome (mean length of
      follow-up, 2 years, 11 months) of meningitis was death in 26 patients (8.2%) and
      sequelae in 49 (16.0%), including 26 children with multiple residual impairment.
      Tuberculous, pneumococcal, and GBS meningitis with a poor outcome increased
      during the late period (1989-1993) of the 10-year study. The annual infant
      mortality rate for purulent meningitis decreased from 3.7 to 1.4 per 100,000
      population between 1984 and 1993. The incidence of a poor outcome (death and
      sequelae) in newborns decreased by half during the late period.

PMID- 8736411
TI  - Mitochondrial encephalomyopathies presenting with features of autonomic and
      visceral dysfunction.
AB  - Three children are reported with mitochondrial encephalomyopathy who presented
      with autonomic dysfunction. Autonomic dysfunction included gastrointestinal
      dysmotility, apnea, cardiac arrhythmias, decreased lacrimation, supersensitivity
      to metacholine, altered sweating, and postural hypotension. These patients
      illustrate that in some mitochondrial encephalomyopathies autonomic features may
      be prominent and can mimic the clinical features associated with hereditary
      sensory and autonomic neuropathies.

PMID- 8736412
TI  - Vertebral artery dissection: issues in diagnosis and management.
AB  - Vertebral artery dissection is an uncommon cause of stroke in children. Accuracy
      of diagnosis by magnetic resonance angiography (MRA) instead of invasive
      transfemoral angiography (TFA) has been controversial. The need for
      anticoagulation and duration of such therapy is also arguable. We report 2 boys
      with vertebral artery dissection: one, aged 7 years, presented with hemiparesis
      and seizures and the other, aged 4 years, presented with ataxia. Each boy's
      initial MRA was not interpreted as delineating occlusive lesions to explain the
      posterior circulation infarcts visualized on computed tomography and magnetic
      resonance imaging scans. However, subsequent MRAs were suspicious for vertebral
      artery dissection, which was confirmed by TFA. Both children were treated with
      anticoagulation therapy. The first patient continued to manifest evidence of new
      infarcts despite treatment (initially with aspirin alone, followed by
      anticoagulation with heparin and warfarin), and is now maintained on a
      combination of high dose warfarin and aspirin. The second patient is now
      maintained on aspirin alone after initial anticoagulation for 6 months with
      heparin followed by warfarin. A high index of suspicion for vertebral artery
      dissection may allow diagnosis on the basis of MRA alone. Previous reports have
      indicated good outcomes of vertebral artery dissection in children and adults
      irrespective of anticoagulation treatment. Our experience suggests that
      anticoagulation may be beneficial in preventing further strokes caused by the
      dissection.

PMID- 8736413
TI  - Down syndrome and moyamoya disease: presentation with subarachnoid hemorrhage.
AB  - Moyamoya disease in childhood is frequently accompanied by manifestations of
      ischemia; cerebral hemorrhage is unusual in patients younger than 15 years of
      age. Previous studies suggest an association of childhood moyamoya disease, which
      is often bilateral, with Down syndrome. Possible etiologic factors of moyamoya
      disease in Down syndrome are discussed.

PMID- 8736414
TI  - From conversion hysteria to somatisation to abnormal illness behaviour?

PMID- 8736415
TI  - Psychosocial factors and physical illness in primary care: promoting the
      biopsychosocial model in medical practice.

PMID- 8736416
TI  - Cynical hostility, anger, and resting blood pressure.
AB  - Research on associations of anger and hostility with resting blood pressure (BP)
      has generally ignored their interrelationships. The present study examined the
      individual and joint relationships of cynical hostility, anger-in, anger-out, and
      anger frequency with resting BP using the Cook-Medley Hostility Scale and the
      Spielberger anger scales. Multiple regressions were conducted on data from a
      community sample of 105 men and women to examine the main and interactive effects
      of anger and hostility on BP, controlling for established physical covariates.
      Diastolic BP was inversely related to anger-in scores in men and women. Systolic
      and diastolic BP were positively associated with Ho (hostility) score only in
      women. No confounding or interactive effects of hostility and anger on BP were
      found. It is suggested that the sex-specific link between cynical hostility and
      BP may reflect a chronic mismatch between the social cognitions of cynically
      hostile women and some of the cultural norms that govern women's social lives.

PMID- 8736417
TI  - Modification of smoking habits five months after myocardial infarction:
      relationship with personality characteristics.
AB  - The relationship between personality characteristics and spontaneous modification
      of smoking habits was assessed in 164 patients after their first myocardial
      infarction (MI). Smoking habits before the MI were investigated in retrospect and
      5 months later. Smoking appeared to have decreased significantly. Persistent
      smokers could be differentiated from nonsmokers and exsmokers by a significantly
      high level of state-anxiety and depression. Young persistent smokers had a high
      level of depression; elderly persistent smokers were highly anxious and had a low
      level of somatization. The relationship between smoking behaviour modification
      and personality characteristics is discussed in association with intervention
      programmes.

PMID- 8736418
TI  - Cardiac Depression Scale: validation of a new depression scale for cardiac
      patients.
AB  - Assessing the effect of interventions on quality of life in cardiac patients
      lacks sensitivity because there is no specifically validated scale for measuring
      depression in cardiac patients. A questionnaire of 35 items (selected for face
      validity) was given to 246 cardiac outpatients (age 59.3 +/- 14.1 years, 159
      male, 87 female). The Beck Depression Scale was then administered, followed by
      blinded clinical rating of depression. The item scores were subjected to common
      factor analysis. Internal consistency was assessed using alpha reliability
      coefficients and clinical validity using Spearman correlation coefficients. The
      final scale consisted of 26 items (alpha reliability coefficient 0.90) in 2
      robust dimensions and 7 subscales. The scale correlated well with clinical rating
      and with the Beck Depression Scale, but without the marked skewness of the
      latter. The behavior of the new Cardiac Depression Scale suggests that it will be
      an excellent measure for studies of outcome in cardiac patients.

PMID- 8736419
TI  - A controlled study of facial mobility treatment in Parkinson's disease.
AB  - The aim of this study was to evaluate the effects of orofacial physiotherapeutic
      treatment (OPT) on the facial mobility of Parkinson's disease (PD) sufferers.
      Sixteen participants with PD were allocated randomly to either the Treatment
      group or the Control group. A short interview between the physiotherapist and
      each subject was videotaped, and 10 random frames of the videotape were selected
      to be used in the facial expression assessment. The quantification of facial
      expressions was achieved by using an objective microcomputer-based measurement
      system, based on a mathematical model of the face (FACEM). A facial outline is
      obtained, as well as 12 facial measures, which represent distances between key
      facial landmarks. The facial assessment was performed on 3 separate occasions,
      that is, baseline (pretreatment), posttreatment, and follow-up (4 weeks later). A
      repeated measures analysis of variance (MANOVA) revealed a significant main
      effect of Time and a significant interaction effect between Time and Group for
      the Mouth-Opening Measure, suggesting that after treatment, members of the
      Treatment group opened their mouths to a greater degree than members of the
      Control group. Within the Treatment group, significant differences between
      pretreatment and posttreatment scores (MANOVA) were found for Mouth-Opening
      Measure and Mid-Top-Lip Measure. Similarly, Mouth-Opening Measure, Mid-Top-Lip
      Measure, Lower-Lip Thickness Measure, Top Eyelid/Iris Intersect Measure and Lower
      Eyelid/Iris Intersect Measure were significant across time from baseline to
      follow-up in the Treatment group only. No significant differences were found on
      any of the facial measures during the same period for members of the Control
      group. These findings suggest that OPT can improve facial movement and that this
      benefit extends in time, beyond the period of OPT itself. Such an increase in
      facial mobility can be expected to modify the "Parkinsonian facies" and
      facilitate the display of facial expressions.

PMID- 8736420
TI  - The relationship between severity of coronary artery disease and vital
      exhaustion.
AB  - The present study investigates the association between the severity of coronary
      artery disease (CAD) and feelings of exhaustion. Vital exhaustion consists of
      three major components: lack of energy, increased irritability, and
      demoralization. Previous studies showed that exhaustion is of predictive value
      for first myocardial infarction (MI). However, these studies could not rule out
      that the state of exhaustion prior to MI was the result of underlying CAD. To
      examine this issue, severity of CAD and cardiac pump function were related to
      feelings of exhaustion in 307 patients who underwent coronary angiography. It was
      found that exhaustion, as assessed by means of the Maastricht Questionnaire (MQ),
      was not related to the severity of CAD (F = 1.17; p = 1.05). Furthermore, a poor
      left ventricular function did not relate to MQ scores (N = 138; F < 1; NS). On
      the other hand, clinical variables (duration of complaints, exercise performance,
      peripheral vascular disease, and dyspnea), use of medication (nitrates, beta
      blocking agents, calcium antagonists, and diuretics), and demographic
      characteristics (gender and education) were associated with MQ scores. Multiple
      regression analysis showed that demographic variables (lower education, younger
      age, and female gender) were the predominant predictors of exhaustion. In
      addition, dyspnea, peripheral vascular disease, and the use of medication related
      significantly to exhaustion scores (R2 = 0.13; F = 4.8; p < 0.001). We conclude
      that neither the extent of CAD nor impaired cardiac pump function is related to
      feelings of exhaustion in patients referred for coronary angiography. Therefore,
      the previously reported association between exhaustion and future MI is not
      likely to be caused by underlying coronary disease.

PMID- 8736421
TI  - Factors associated with depression in a heterogeneous HIV-infected sample.
AB  - The present study examined factors contributing to depressive symptomatology in a
      low SES, heterogeneous HIV seropositive sample. The sample was comprised of 120
      HIV-infected patients who completed psychosocial measures upon their initial
      visit to an outpatient HIV clinic. Length of time since HIV seropositive
      notification and HIV-related symptomatology were also assessed. Social support,
      major life stress, and HIV-related symptomatology were significantly associated
      with depression. Perceived availability of social support accounted for the
      greatest variance in depression scores. Length of time since seropositive
      notification was not significantly associated with depression. These findings
      extend previous research with middle-class, homosexual, white males to the
      rapidly growing minority, heterosexual, and low SES populations and point to the
      need for the inclusion of social support interventions in the provision of
      services of these individuals.

PMID- 8736422
TI  - Psychologic characteristics associated with acute stressor-induced leukocyte
      subset redistribution.
AB  - This study examined relationships between psychologic characteristics and
      enumerative immune responses to an acute laboratory stressor. Lymphocyte subsets
      were measured in 104 subjects at rest and following a 6-minute laboratory
      naturalistic speaking stressor. Multiple linear regression was utilized to assess
      relationships between immune reactivity (change scores) and anger expression,
      hostility, anxiety, depression, and stress. The task resulted in significant
      increases over baseline in WBC (p < 0.001), T-suppressor/cytotoxic CD8 cells (p =
      0.010) natural killer CD56 cells (p < 0.0001), and CD57 (p < 0.0001) cells, and
      significant decreases in T-cells (p = 0.012), T-helper cells (p = 0.003), B-cells
      (p < 0.001), and the T-helper/suppressor ratio (p < 0.001). In general, the
      regression suggested that moderate associations exist between certain psychologic
      attributes and acute subset redistribution. For example, the increase in natural
      killer cell subsets was significantly negatively associated with anger
      expression, hostility, and depression. Suppressor/cytotoxic (CD8) cell reactivity
      was associated with baseline as well as with the task-induced changes in anxiety.
      B-cell (CD19) responses were related to the subject's age, expression of anger,
      and depression scores. As with the cardiovascular reactivity literature, these
      findings suggest that a relationship exists between certain psychologic
      characteristics such as anger and anxiety and immune reactivity to acute stress.

PMID- 8736423
TI  - The psychological impact on staff of caring for people with serious diseases: the
      case of HIV infection and oncology.
AB  - Psychological stress and work-related burnout in staff working with AIDS and with
      cancer patients were compared using a self-report method of assessment. Measures
      included the General Health Questionnaire (GHQ), Maslach Burnout Inventory (MBI),
      and the Social Adjustment Scale (SAS-M). More than 80% of those staff who were
      approached responded to the questionnaire, including 70 doctors and nurses
      working with people with AIDS and 41 doctors and nurses working in oncology. More
      than a third of staff had substantial levels of psychological morbidity, and
      about a fifth had significant levels of work-related stress. Factors associated
      with the presence of high levels of psychological morbidity and with abnormal
      levels of emotional exhaustion, depersonalization, and concerns about personal
      accomplishment were identified. Staff described the work situations with which
      they had difficulty dealing and some of the coping strategies they used. The
      findings confirm that staff working with people with cancer or AIDS experience
      psychological difficulties of the kind likely to respond to interventions aimed
      at improving their ability to cope with work-related stresses. The mental health
      services could play an important role in carrying out research in this field and
      in providing practical help to deal with staff's difficulties.

PMID- 8736424
TI  - Urinary dopamine and noradrenaline outputs during oral salt loading in healthy
      Chinese subjects with a family history of hypertension.
AB  - 1. Increased salt sensitivity has been reported in first-degree relatives of
      hypertensive patients. To determine if the enhanced effect of oral salt intake on
      blood pressure in such individuals is related to abnormal renal dopamine (DA) or
      sympathetic nervous system responses, we studied the effects of two different
      sodium intakes (20 mmol/day followed by 220 mmol/day each given for 5 days) on
      mean arterial pressure (MAP) and urinary excretion of sodium, free DA and
      noradrenaline (NA) in seven normotensive Chinese subjects with a family history
      of hypertension. We compared these results with those we have reported previously
      for normotensive subjects without a family history of hypertension. 2. There was
      a seven- to ten-fold increase in sodium excretion (P < 0.02). MAP increased from
      80.1 +/- 2.5 to 83.1 +/- 2.1 mmHg (P < 0.05). A 23% increase in urine DA (P <
      0.02) was seen on day 1. From day 2 to day 5, the increase in urine DA (12-15%)
      became attenuated and reached statistical significance only on days 2 and 5.
      There was no significant change in urinary NA output. 3. As in healthy Chinese
      subjects without a family history of hypertension, those with a family history
      showed an early but unsustained rise in urine DA during oral sodium loading. Such
      an increase was rather small compared to the increase in urine sodium, suggesting
      that renal DA only contributes partly to the natriuretic response. Unlike those
      with no family history, subjects with a family history showed an increase in
      blood pressure after oral salt loading, possibly because of inadequate
      suppression of sympathetic nervous system activity.

PMID- 8736425
TI  - cGMP release in rat mesenteric arterioles and in conduit mesenteric artery.
AB  - 1. Relaxing factors were studied in two perfused preparations of the same
      vascular area in the rat: resistance mesenteric arterioles and conduit mesenteric
      artery. 2. In both preparations, an acetylcholine (ACh) infusion inhibited
      noradrenaline (NA) vasoconstrictor effects but at a ten-times greater
      concentration in conduit artery than in resistance arterioles. 3. Endothelium
      destruction with hypotonic Krebs solution did not change basal perfusion
      pressure, but increased NA responses and suppressed ACh inhibitory effects in
      arterioles and arteries. Likewise, L-NAME abolished the ACh effect in mesenteric
      arterioles but only reduced it in mesenteric artery. 4. Basal release of cyclic
      GMP was significantly greater in mesenteric artery than in resistance arterioles.
      By contrast, ACh-induced cGMP release was higher in mesenteric arterioles.
      Endothelium removal did not change basal release of cGMP in mesenteric arterioles
      but reduced it in mesenteric artery. 5. These results suggest that in basal
      conditions several relaxing factors are present in higher concentrations in
      conduit mesenteric artery than in resistance mesenteric arterioles. However,
      although it releases higher basal amount of cGMP, this vessel has a reduced role
      in vascular control than do smaller arteries.

PMID- 8736426
TI  - Interactions of the cardiac chronotropic effects of rilmenidine with the
      autonomic nervous system in conscious dogs: comparison with clonidine.
AB  - 1. The cardiac chronotropic effects of rilmenidine (10-100 micrograms kg-1) and
      clonidine (1-10 micrograms kg-1) were studied in conscious dogs with chronic
      atrioventricular block. 2. Rilmenidine and clonidine initially (< 3 min)
      decreased atrial rate, although the effect was not related to dose. More
      lastingly, ventricular rate was decreased in a dose-related manner (ratio, 1:21).
      Rilmenidine lowered mean blood pressure only at 100 micrograms kg-1, while
      clonidine had the same effect at doses of 5 micrograms kg-1 upward (ratio, 1:15).
      3. When administered after atropine and pindolol, rilmenidine (50 micrograms kg
      1) produced a decrease in atrial rate, with an identical intensity but longer
      duration than under basal conditions. When clonidine (2.5 micrograms kg-1) was
      given after atropine, no chronotropic atrial effect was observed. However, when
      clonidine (2.5 micrograms kg-1) was given after pindolol, it produced a decrease
      in atrial rate that was more marked, both in intensity and duration, than under
      basal conditions. After phenoxybenzamine, rilmenidine decreased atrial rate with
      a more marked and lasting effect than observed under basal conditions. Clonidine
      produced a bradycardic atrial effect identical to the basal effect. After
      yohimbine, rilmenidine and clonidine decreased atrial rate with an intensity
      similar to that under basal conditions, although the time course was totally
      different. 4. When given after atropine, rilmenidine (50 micrograms kg-1) and
      clonidine (2.5 micrograms kg-1) decreased ventricular rate as under basal
      conditions, whereas after pindolol and phenoxybenzamine, both drugs decreased
      ventricular rate less markedly than under basal conditions, both in intensity and
      duration. After yohimbine, rilmenidine and clonidine produced no chronotropic
      ventricular effect. 5. These results show that (a) the initial atrial bradycardia
      caused by rilmenidine results from both a decrease in sympathetic tone and an
      increase in cholinergic activity; while the effect of clonidine is caused mainly
      by the enhancement of cholinergic activity. For both drugs, alpha 2-adrenoceptors
      are involved at least in the initiation of the effect; (b) the very short
      duration of atrial bradycardia may result from reflex buffering in response to
      ventricular bradycardia. This buffering is less effective when heart rate was
      high; and (c) the ventricular bradycardia caused by both drugs is mainly the
      result of a decrease in sympathetic tone in response to the stimulation of alpha
      2-adrenoceptors. The results also suggest that negative chronotropic postsynaptic
      alpha 2-adrenoceptors could be involved in the ventricular bradycardia.

PMID- 8736427
TI  - Drugs for treatment of benign prostatic hyperplasia: affinity comparison at
      cloned alpha 1-adrenoceptor subtypes and in human prostate.
AB  - 1. We have previously shown that among alpha 1-adrenoceptor antagonists used or
      investigated for the treatment of benign prostatic hyperplasia, tamsulosin
      discriminates alpha 1-adrenoceptor subtypes in rat tissues whereas alfuzosin and
      naftopidil do not. We now expand these studies to additional drugs (doxazosin,
      terazosin) being used and/or investigated for this purpose, and have evaluated
      all of these drugs at cloned subtypes and in human prostate. 2. Competition
      binding studies were performed with [3H]-prazosin in membrane samples from rat
      spleen, kidney and cerebral cortex and human prostate and with cloned alpha 1
      adrenoceptors expressed in COS cells. Doxazosin and terazosin did not
      discriminate alpha 1-adrenoceptor subtypes in rat kidney and cerebral cortex. In
      contrast, the subtypes present in the tissues were well discriminated by the
      alpha 1A-adrenoceptor-selective reference drug WB 4101. 3. Alfuzosin, doxazosin,
      naftopidil and terazosin did not discriminate cloned alpha 1-adrenoceptor
      subtypes transiently expressed in COS cells whereas tamsulosin and WB 4101 did.
      4. In human prostate, alfuzosin, doxazosin, naftopidil and terazosin did not
      discriminate the alpha 1-adrenoceptor subtypes present in this tissue whereas
      tamsulosin and the alpha 1A-adrenoceptor-selective reference drugs WB 4101,
      phentolamine and 5-methylurapidil did. Based on data with the alpha 1A
      adrenoceptor-selective drugs, human prostate contains alpha 1A- and alpha 1B
      adrenoceptors in an approximate 70:30% ratio. 5. We conclude that tamsulosin, in
      common with WB 4101, but in contrast to alfuzosin, doxazosin, naftopidil, and
      terazosin is selective for alpha 1A-adrenoceptors which appear to dominate in the
      human prostate; the therapeutic relevance of this selectivity remains to be
      assessed in clinical studies.

PMID- 8736428
TI  - Inhibitory effect of propofol on sympathetic neurotransmission results in changes
      of plasma neuropeptide Y in rats.
AB  - 1. The effects of propofol on sympathetic neurotransmission and changes of plasma
      level of neuropeptide Y-like immunoreactivity (NPY-ir) were investigated in rats.
      2. Intraperitoneal injection of propofol into rats lowered the systemic blood
      pressure and plasma NPY-ir in a dose-dependent manner. 3. Decrease of plasma NPY
      ir induced by propofol was not modified in adrenalectomized rats. In the
      activation of adrenergic neurotransmission by a ganglionic nicotinic agonist,
      elevation of plasma NPY-ir was also reduced by propofol indicating the direct
      effect on peripheral adrenergic nerve terminals. 4. Plasma level of NPY-ir
      reversed in parallel with the recovery of anaesthesia induced by propofol. After
      an intracerebroventricular injection of propofol into the rats, both the lowering
      of plasma NPY-ir and the induction of anaesthesia were observed. Thus, a central
      nervous system effect of propofol can also be considered in its effect on plasma
      NPY-ir. 5. The data suggest that propofol has the ability to lower plasma NPY-ir
      in rats through an inhibition of adrenergic neurotransmission via central nervous
      pathway and/or peripheral nerve terminal blockade.

PMID- 8736429
TI  - Involvement of nitric oxide in the smooth muscle tone of the isolated canine
      spleen and the responses to acetylcholine and substance P.
AB  - 1. The canine isolated spleen was perfused at constant flow with warmed (37
      degrees C) Krebs solution while the splenic arterial perfusion pressure (SAPP)
      and spleen weight were recorded continuously. An augmented smooth muscle tone was
      maintained by a continuous intra-arterial infusion of noradrenaline (0.01-0.1
      mumol min-1) throughout the experiment. 2. Intra-arterial infusion of
      indomethacin (5.6 microM) significantly elevated (P < 0.05) the augmented
      vascular tone and the subsequent infusion of L-NAME (10 microM) further raised
      this vascular tone significantly (P < 0.01). 3. The splenic vasoconstrictor
      response to L-NAME was significantly (P < 0.05) reduced by the subsequent
      infusion of L-arginine (300 microM) but not of D-arginine (300 microM). 4.
      Neither L-NAME nor D-NAME had any effect on the basal vascular tone or the spleen
      weight in conditions of either basal or augmented tone. 5. Bolus injection of
      acetylcholine, substance P, sodium nitroprusside and isoprenaline caused short
      lasting reductions in the SAPP. 6. The splenic vasodilator responses to ACh and
      SP, but not those to SNP and ISO, were significantly (P < 0.05) reduced by the
      infusion of L-NAME (10 microM), methylene blue (30 microM) but not of D-NAME (10
      microM). 7. The reductions in the vasodilator responses to ACh and SP caused by L
      NAME were partially reversed by L-arginine (300 microM), but not by D-arginine
      (300 microM). 8. The results demonstrate the contribution of nitric oxide (NO)
      release to the maintenance of the augmented splenic vascular tone and also the
      contribution of NO to the splenic vasodilator responses to ACh and SP.

PMID- 8736431
TI  - Effects of DQ-2511 on neutral activity in afferent and efferent loops of gastric
      vago-vagal reflex pathways in the rat.
AB  - 1. DQ-2511 is a new substituted benzamide compound that has gastric prokinetic
      properties. Actions of the drug on neural discharge in the innervation of the
      stomach of anaesthetized rats were studied. Standard extracellular methods of
      multi-unit recording were used to study rates of firing in afferent and efferent
      filaments teased from gastric branches of the vague nerve. 2. Decreased firing in
      gastric vagal efferents was associated with increased rates of discharge in the
      gastric afferents. 3. Intravenous application of DQ-2511 resulted in increased
      frequency of firing in the efferents in association with decreased rate of
      discharge in afferent fibres. 4. Application of cholecystokinin octapeptide
      (CCK8) suppressed activity in the gastric efferents which occurred coincident
      with the elevated discharge in the afferents. Pretreatment with DQ-2511 blocked
      the actions of CCK8. 5. The results suggest that the gastric prokinetic action of
      DQ-2511 may involve suppression of activation of afferents in the sensory
      component of gastric inhibitory vago-vagal reflex pathways.

PMID- 8736430
TI  - Augmentation of neurally evoked cholinergic bronchoconstrictor responses by
      prejunctional NK2 receptors in the guinea-pig.
AB  - 1. We examined the effect of exogenously administered tachykinins, neurokinin A
      (NKA), substance P (SP) and neurokinin B (NKB) on neurally mediated cholinergic
      bronchoconstrictor responses in guinea-pigs. 2. Electrical stimulation of regions
      in the dorsal medulla oblongata produced a cholinergic bronchospasm that was not
      affected by depletion of endogenous tachykinins with capsaicin pretreatment (50
      mg kg-1, s.c., 1 week earlier) or by pretreatment with the neutral endopeptidase
      inhibitor, phosphoramidon (3 mg kg-1, i.v.). 3. Infusion of NKA (0.03-0.1
      microgram kg-1 min-1), SP (1 microgram kg-1 min-1) or NKB (1 microgram kg-1 min
      1) potentiated the bronchoconstrictor response to electrical stimulation of the
      dorsal medulla. The doses of tachykinins tested were subthreshold for direct
      activation of airway smooth muscle, because they were devoid of direct
      bronchoconstrictor effects. The relative rank order potency for augmentation of
      centrally induced bronchospasm was NKA > NKB approximately SP, suggesting
      activation of the NK2 receptor subtype. 4. Infusion of NKA, SP and NKB had no
      effect on bronchoconstrictor responses to i.v. methacholine (1 microgram kg-1)
      indicating that a prejunctional neural mechanism of action was responsible for
      the effects on CNS stimulation-induced bronchospasm. 5. Potentiation of the
      bronchoconstrictor response to dorsal medullary stimulation produced by infusion
      of NKA was blocked by pretreatment with the NK2 antagonist SR 48968 (1 mg kg-1,
      i.v.) but not by the NK1 antagoinst CP 96,345 (1 mg kg-1, i.v.). 6. The
      potentiation of CNS-induced bronchospasm produced by infusion of SP was partially
      inhibited by CP 96,345 (1 mg kg-1, i.v.) but not by SR 48968 (1 mg kg-1, i.v.).
      Treatment with combined SR 48968 (1 mg kg-1, i.v.) and CP 96,345 (1 mg kg-1,
      i.v.) completely blocked the SP-induced potentiation of CNS-stimulated
      bronchospasm. 7. These results identify an important modulatory role for NK2
      receptors, located at prejunctional sites on parasympathetic nerves, on
      cholinergic bronchoconstrictor responses in guinea-pigs. 8. It is proposed that
      substances that release tachykinins from airway sensory nerves, e.g. inflammatory
      mediators or irritants, may induce hyperresponsiveness of cholinergic
      bronchomotor responses by activation of NK2-receptors on parasympathetic airway
      nerves. Furthermore, these studies indicate that endogenous tachykinins are not
      involved in the maintenance of basal cholinergic bronchomotor tone in the intact
      guinea-pig.

PMID- 8736432
TI  - Hypothalamic cellular and molecular mechanisms helping to satisfy axiomatic
      requirements for reproduction.
AB  - In the absence of universal equations expressing neurobiological findings, the
      safest theoretical approach for the neuroendocrinologist is to start from
      axiomatic requirements for biologically adaptive neural mechanisms, in our case
      for reproduction. From this emerge two themes: the likely importance of
      interactions between internal (hormonal) and external signals in controlling gene
      expression relevant to reproductive functions; and, second, the vision of
      molecular interactions on DNA subserving environmental impacts on reproduction.
      The first theoretical notion has so far yielded data showing a role for synaptic
      inputs during the onset of estradiol actions for the hormone's induction of
      enkephalin mRNA, a finding which parallels earlier behavioral results. As well,
      noxious somatosensory inputs interact with estrogens and progesterone in their
      influence on enkephalin gene expression. The second theme led to novel
      investigations of thyroid influences on reproductive molecular biology and
      behavior, including the ability of exogenous or endogenous thyroid hormones to
      reduce female mating responses. Since elevated thyroid hormone levels could
      signal environmental cold, our experiments offer the possibility of explaining
      ethological facts at a molecular level. More generally, nuclear hormone receptor
      interactions on the surface of DNA may offer a new level of neural integration
      revealed first by hormone effects in neuroendocrine cells.

PMID- 8736433
TI  - Effects of long-term treatment with antidepressant drugs on proopiomelanocortin
      and neuropeptide Y mRNA expression in the hypothalamic arcuate nucleus of rats.
AB  - Antidepressant drugs have in common a delayed onset of clinical efficacy. In
      rats, long-term, daily administration of four different types of clinically
      effective antidepressant drugs results in decreased corticotropin releasing
      hormone (CRH) mRNA expression levels in the hypothalamic paraventricular nucleus
      (PVN). Because a subpopulation of neuropeptide Y (NPY) and proopiomelanocortin
      (POMC) neurons in the hypothalamic arcuate nucleus (Arc) projects to the PVN, we
      measured NPY and POMC mRNA expression in the Arc using in situ hybridization
      histochemistry at several time points following daily administration of four
      different antidepressant drugs. After 14 and 56 days of imipramine treatment, Arc
      NPY mRNA levels are decreased to 85% and 75% of control levels, but are unchanged
      compared to control after one or five days of treatment. Arc POMC mRNA levels are
      unchanged compared to controls at 1, 5, 14, or 56 days following imipramine
      treatment. Unlike after imipramine, Arc NPY and POMC mRNA levels are increased
      significantly to 134-172% of control following 56-day treatment with the
      antidepressant drugs fluoxetine, phenelzine, or idazoxan. The divergent effects
      of imipramine vs the other 3 antidepressant drugs on Arc NPY mRNA expression are
      similar to the pattern of changes in tyrosine hydroxylase (TH) mRNA expression
      levels in the locus coeruleus (LC) using the same experimental paradigm, but are
      different from the unidirectional depressive effects of all four drugs on CRH
      mRNA expression in the PVN. Thus, the Arc NPY and LC noradrenergic systems may
      act coordinately in mediating antidepressant effects. The present data are
      consistent with the delayed onset of clinical efficacy for antidepressant drugs,
      and suggest that Arc NPY and POMC neurotransmitter systems play a role in the
      pathophysiology of depression.

PMID- 8736434
TI  - The temporal pattern of mating-induced immediate-early gene product
      immunoreactivity in LHRH and non-LHRH neurons of the estrous ferret forebrain.
AB  - The mating-induced preovulatory surge of luteinizing hormone (LH) lasts for at
      least 12 h in the female ferret. This prolonged increase in circulating LH is
      presumably accompanied by a corresponding elevation in the activity and output of
      luteinizing hormone-releasing hormone (LHRH) neurons projecting to the
      hypothalamic-hypophyseal portal blood vessels and adenohypophysis. We used the
      protein products of the immediate early genes (IEGs) c-fos, and c-jun as markers
      of neural activation in order to determine whether a sub-population of LHRH
      neurons is differentially activated by mating and whether non-LHRH neurons in
      specific forebrain regions are selectively activated at different times during
      the mating-induced preovulatory LH surge. In Experiment 1, estrous female ferrets
      were perfused 0.5, 1.5, 3.0, 6.0 or 12.0 h after receiving one 5-min intromission
      from a male or after being placed alone in a testing cage for 20 min. Fos-like
      immunoreactivity (Fos-IR; Oncogene Ab-2 antiserum) and LHRH-like immunoreactivity
      (LHRH-IR; LR-1 antiserum) were visualized. The percentage of Fos-IR LHRH neurons
      was significantly augmented 1.5 h after mating but had returned to basal levels
      by 3.0 h. The double-labeled LHRH neurons were concentrated in the caudal medio
      basal hypothalamus. In non-LHRH neurons the number of Fos-IR neural nuclei was
      significantly increased by mating in the medial preoptic area (MPOA), bed nucleus
      of the stria terminalis (BNST), medial amygdala (MA), ventrolateral hypothalamus
      (VLH), and midbrain central tegmental field (CTF) 1.5 h after mating but, as in
      LHRH neurons, had returned to basal levels by 3.0 h. In Experiment 2, estrous
      females were perfused 1.5 h or 8.0 h after either receiving one 5-min
      intromission or being placed alone in a testing cage, and the brains were
      processed for LHRH and c-Fos-like (DCH-1, Dr Gerard Evan), c-Jun-like (Jun-IR;
      Oncogene Ab-2) or Egr-1-like (Egr-IR; Santa Cruz) immunoreactivity. The
      percentage of LHRH neurons colabeled with both Fos-IR and Jun-IR was
      significantly greater in the 1.5 h group than in the unpaired group. Again, the
      induction of these IEG products occurred in LHRH neurons in the caudal medio
      basal hypothalamus. Mating significantly increased the number of Fos-IR non-LHRH
      neural nuclei in the MPOA, BNST, MA, VMH and CTF, as well as the number of Egr-IR
      nuclei in the MPOA, BNST and MA in the 1.5 h group. By contrast, the number of
      Jun-IR non-LHRH neurons was unaffected by mating. In these Experiments we have
      identified a sub-population of LHRH neurons which, using Fos and Jun as markers
      of neural activation, is activated by mating and may be differentially involved
      in the generation of the preovulatory LH surge. Although the LHRH system is
      presumably activated throughout the duration of the 12 h preovulatory LH surge, c
      Fos and c-Jun immunoreactivity in LHRH neurons is augmented only transiently. Fos
      IR and Egr-IR in non-LHRH neurons show a similar time-course. Together, these
      results suggest that the presence of augmented levels of these proteins is not
      required for the maintenance or termination of the preovulatory output of LHRH.

PMID- 8736435
TI  - Compression of the pituitary stalk elicits chronic increases in CSF vasopressin,
      oxytocin as well as in social investigation and aggressiveness.
AB  - The neurochemical and behavioural effects of a novel stereotaxic surgical method
      developed for interrupting the nerve fibres running through the rat pituitary
      stalk to the posterior pituitary gland was studied. The cerebrospinal fluid (CSF)
      vasopressin (AVP) and oxytocin (OT) content as well as changes in aggressiveness
      were measured in rats one week and one month after the surgical intervention. The
      main results are as follows: (1) the compression of the pituitary stalk elicits a
      chronic increase in water consumption, as well as in CSF vasopressin and oxytocin
      content; (2) the surgical intervention increased the frequency of clinch fighting
      after one week. The increase in aggressiveness accentuated after one month and,
      in addition, operated animals showed reduced scores of resting while exploratory
      and social behaviours increased; (3) there was a strong positive correlation
      between water consumption, vasopressin, and aggressiveness; (4) oxytocin changes
      showed a positive correlation with variation in social behaviour. The surgical
      intervention may serve as a model for lesions of the pituitary stalk and
      formation of ectopic neurohypophyses in humans.

PMID- 8736436
TI  - PACAP and VIP stimulate Ca2+ oscillations in rat gonadotrophs through the
      PACAP/VIP type 1 receptor (PVR1) linked to a pertussis toxin-insensitive G
      protein and the activation of phospholipase C-beta.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive
      intestinal polypeptide (VIP) are hypothalamic factors that play roles in the
      regulation of anterior pituitary cell activity. PACAP exists in 2 forms
      physiologically, a 38 amino acid form (PACAP38) and a form possessing the N
      terminal 27 amino acids of PACAP38 (PACAP27). We have previously shown that
      PACAP38 stimulates an increase in [Ca2+]i in rat gonadotrophs. In an attempt to
      identify the PACAP receptor type underlying this effect, we compared the potency
      of PACAP38, PACAP27 and VIP to stimulate Ca2+ changes in identified single rat
      gonadotrophs. All 3 peptides at 100 nM were capable of stimulating high amplitude
      Ca2+ oscillations, which were also observed in the absence of extracellular Ca2+.
      The order of potency of these peptides was PACAP38 > PACAP27 > VIP, and a potent
      antagonist of the PACAP/VIP type II binding site ([4-CI-D-Phe6, Leu17]-VIP)
      failed to block these responses, suggesting that these effects are mediated
      through a PACAP/VIP type 1 receptor (PVR1). The Ca2+ responses to PACAP38 and VIP
      were unaffected by overnight treatment of the cells with pertussis toxin (PTX;
      250 ng/ml) indicating that these responses are mediated by a PTX-insensitive G
      protein. Finally, the Ca2+ responses stimulated by PACAP38 and VIP were blocked
      by the phospholipase C-beta blocker U73122 (5 microM). In summary, PACAP
      stimulates Ca2+ oscillations in rat gonadotrophs through the activation of the
      PVR1 linked to a PTX-insensitive G-protein and the activation of phospholipase C
      beta. VIP can stimulate the same pathway in rat gonadotrophs, although it is at
      least 100 fold less potent than PACAP38.

PMID- 8736437
TI  - Suckling-induced Fos-immunoreactivity in subgroups of hypothalamic POMC neurons
      of the lactating rat: investigation of a role for prolactin.
AB  - Attention has recently been focused on lactation-induced modifications of
      activity of neuronal populations in the arcuate nucleus (ARC) of the mediobasal
      hypothalamus. The ARC hosts the tubero-infundibular dopaminergic (TIDA system)
      responsible for the neuroendocrine control of prolactin (PRL), and other non
      neuroendocrine neuronal populations, such as neuropeptide Y (NPY)- and
      proopiomelanocortin (POMC)-containing systems that are important modulators of
      hypothalamic gonadoliberin (GnRH) secretion. Our longstanding interest in the
      functional anatomy of the ARC led us to investigate whether the suckling stimulus
      would trigger an expression of Fos-ir in specific arcuate neuronal populations
      and to possibly characterize responsive neurons by using double-labeling
      immunohistochemistry. Freely nursing lactating females expressed strong Fos-ir in
      neurons of the ARC compared to diestrous females. Fos-ir was encountered in
      neurons not belonging to the TIDA system and that was for a large proportion
      identical to the POMCergic neurons. We showed that, in lactating females
      submitted to suppression of the suckling stimulus by removal of the pups, the
      pattern of expression of Fos-ir is similar to that seen in diestrous females and
      that, a pattern of expression of Fos-ir indistinguishable from that observed
      during free lactation is reinstated a short time after the return of the pups and
      restoration of the suckling stimulus, suggesting that this expression of Fos-ir
      strictly depends upon the presence of the newborns and the suckling stimulus. By
      lowering circulating levels of the PRL with bromocryptine-or PRL antiserum
      treatment, we noticed a decrease in the number of (beta-endorphin + Fos)-ir
      neurons compared to non-injected freely nursing lactating females. By maintaining
      high levels of circulating PRL with haloperidol-treatment, we observed a number
      of colocalizations close to that observed in freely nursing lactating females.
      Our results suggest that during lactation a rostral subgroup of the arcuate
      POMCergic neuronal population is activated at least partially in response to the
      suckling-induced secretion of PRL and that this activation participates in
      maintaining the endocrine and/or metabolic demands of the lactational status.

PMID- 8736438
TI  - Pineal microdialysis of the melatonin in conscious sheep: methodology,
      application to a diurnal rhythm and effect of isoproterenol.
AB  - This paper describes the development of a new technique to measure melatonin
      contents in the pineal gland of moving sheep: the microdialysis. A dialysis probe
      was used to collect extracellular fluid in the sheep pineal gland, but also to
      inject directly into it different drugs such as isoproterenol at a very low
      concentration. The probe was implanted the day before the beginning of the
      experiment in order to obtain low levels of melatonin. This technique makes it
      possible to measure melatonin in the dialysate and plasma of rams submitted to
      8L:16D. No melatonin either in the dialysate or in the plasma was found during
      the light phase. Shortly after lighting off, the melatonin concentration
      increased in the dialysate and plasma and remained stable during the dark phase.
      Melatonin concentrations began to decrease before lighting on and no detectable
      levels were found during the following light phase. The secretion of melatonin
      is, at least, under adrenergic regulation. Local infusion of isoproterenol (90
      microliters at 10(-6) M), an agonist of beta adrenergic receptor, through the
      probe, increased melatonin levels during 2 h, even when infusions were repeated 3
      times. This demonstrates the presence of beta adrenergic receptors. The technique
      presented in this paper could be of considerable interest for studying sheep
      pineal gland and its main secretion, melatonin, for example during diurnal
      rhythms or for studying its regulation.

PMID- 8736439
TI  - Regulation of activin type-II receptor mRNA levels in rat hypothalamus by
      estradiol in vivo.
AB  - A solution-hybridization S1-nuclease protection assay was used to evaluate the
      expression of messenger RNAs for the activin beta A subunit and type II activin
      receptor in adult rat brain. Results indicate the presence of beta A subunit mRNA
      in both hypothalamus and brainstem, with approximately two-fold higher levels in
      brainstem. Levels of activin type II receptor mRNA were similar in the
      hypothalamus of young virgin and 15-day lactating females, and in females in
      which pups were removed after a 5-day lactation period. Male rats castrated
      prepubertally (30 days p.n.) had approximately 220% higher (P < 0.05)
      hypothalamic activin type II receptor mRNA levels than postpubertal, 3-month old
      age-matched sham controls. Two month treatment of castrate rats with estradiol
      (200 ng/g, i.p. every 2 days) reduced hypothalamic activin type II receptor mRNA
      expression to control levels; the same dose of testosterone had no effect. The
      expression of the hypothalamic activin type II receptor gene may be estrogen
      regulated in vivo.

PMID- 8736440
TI  - The relationship between gastro-oesophageal reflux disease and dental erosion.
AB  - It is well known that acid regurgitated from the stomach into the mouth will
      erode teeth. Conditions such as anorexia and bulimia nervosa, chronic alcoholism
      and gastric disturbances cause palatal dental erosion. The common factor in these
      conditions is the role played by the stomach and oesophagus in the acid movement.
      Acid moving through the lower oesophageal sphincter into the oesophagus is
      described as gastro-oesophageal reflux (GOR). In some patients the acid movement
      becomes chronic, painful and requires treatment and is termed gastro-oesophageal
      reflux disease (GORD). It is felt by many gastroenterologists that GORD is a
      failure of the anti-reflux mechanism, which is predominantly controlled by the
      lower oesophageal sphincter (LOS). Regurgitation is the reflux of gastric juice
      through the upper oesophageal sphincter and into the oral cavity. Once the acid
      has reached the mouth the potential exists for damage to the teeth. This paper
      reviews the role of GOR, GORD and regurgitation in the aetiology of dental
      erosion.

PMID- 8736441
TI  - Influence of paste temperature at curing on conversion rate and bending strength
      of light-cured dental composites.
AB  - Pastes of three dental composites were tempered to 20 degrees C, 37 degrees C and
      60 degrees C. Test specimens (22 x 2 x 2 mm) were cured by light and stored in
      deionized water. Three-point bending strength was measured after 1 h and after 24
      h. Degree of conversion on the surface exposed to the curing light and the
      opposite surfaces at the bottom of the mould was analysed by Fourier transform
      infrared (FTIR) after 1 h. After 1 h, specimens produced using the pastes cured
      at 60 degrees C showed significantly higher bending strength than the specimens
      produced using pastes cured at 20 degrees C and 37 degrees C. However, after 24 h
      the composites pretempered at the lower temperatures had developed the same level
      of bending strength as the composites cured at 60 degrees C. An increase in the
      degree of conversion with increased paste temperature was found in all materials
      after 1 h.

PMID- 8736442
TI  - An in vitro microleakage study of a new multi-purpose dental adhesive system.
AB  - Despite the advances made in the field of adhesive dentistry, microleakage still
      remains an area of concern, as a secure seal to dentine and cementum still cannot
      be achieved with certainty. This project compared the effectiveness of a new
      adhesive, Scotchbond Multi-Purpose Dental Adhesive System (SBMP) with an
      established product, Gluma Bonding System (Gluma) in preventing microleakage and
      the influence of storage, thermal and load cycling on microleakage patterns. In
      uncycled specimens, Gluma Bonding System had significantly less leakage (P <
      0.01) at both occlusal and cervical margins. Thermocycling of composite
      restorations utilizing SBMP resulted in a significant decrease (P < 0.05) at the
      occlusal margins but had no effects on cervical leakage. Mechanical loading had
      no influence on leakage patterns either cervically or occlusally. Three months'
      storage and combined treatment resulted in a significant decrease in leakage (P <
      0.05) at the occlusal margins.

PMID- 8736443
TI  - Biological effects of palladium and risk of using palladium in dental casting
      alloys.
AB  - In dentistry, palladium is a very common component of dental casting alloys of
      all types, and its use has increased over the past several decades in response to
      the increased cost of gold. However, there have been recent controversies,
      particularly in Germany, over possible adverse biological effects of using
      palladium in dental alloys. Therefore, the purpose of this paper is to review the
      known biological effects of palladium and the likelihood that these effects can
      be caused by dental alloys which contain palladium. In an ionic form and at
      sufficiently high concentrations, palladium has toxic and allergic effects on
      biological systems. Palladium allergy almost always occurs in individuals who are
      sensitive to nickel. The carcinogenic potential of the palladium ion is still
      unclear, although there is some evidence that it is capable of acting as a
      mutagen. However, there are no well documented cases of adverse biological
      reactions to palladium in the metallic state. Furthermore, in spite of the
      potential adverse biological effects of palladium ions, the risk of using
      palladium in dental casting alloys appears to be extremely low because of the low
      dissolution rate of palladium ions from these alloys.

PMID- 8736444
TI  - Studies of changes in occlusion after the insertion of complete dentures. Part I.
AB  - The present study aims to investigate changes in the occlusion of complete
      dentures after their insertion. A total of 85 edentulous patients were provided
      with new complete dentures. Their individual hinge axes were determined using
      mechanical axiography and the upper finished dentures were transferred by
      facebows to Dentatus articulators. The lower dentures were mounted according to
      an intraoral central bearing point (CBP) registration and equilibrated in
      terminal hinge position. An articulator specially modified for measurements in
      the condylar area was used. The differences between the positions of the condylar
      balls with CBP registration and those after equilibrating the occlusion were
      determined. On average, 19 days after insertion, 71 patients took part in a
      follow-up examination. As in the first session, the terminal hinge position was
      registered with the CBP method using the apex of the Gothic arch. Thus, the
      positions of the condylar balls immediately after the new registration could be
      compared with those in equilibrated intercuspation 3 weeks earlier. The
      differences were found to be 0.5 +/- 0.4 mm (0-2.9 mm) in the three axes
      (sagittal, coronal and horizontal). They are thought to result from settling into
      the denture bearing tissues and also from neuromuscular adjustment of the
      masticatory system. Compulsory remounting of complete dentures after insertion is
      therefore recommended.

PMID- 8736445
TI  - Comfortable zone of the mandible evaluated by the constant stimuli method.
AB  - For evaluation of the comfortable zone (CZ) and the most comfortable position
      (MCP) of the occlusal vertical relation of the mandible, the constant stimuli
      method with three subjective categories of judgements was applied in 10
      edentulous subjects. The evaluated CZ was stable and about 3 mm in width. The
      occlusal vertical dimension (OVD) of the existing dentures was found to be
      located within the CZ in nine of the 10 subjects.

PMID- 8736446
TI  - Alteration in the bite force and EMG activity with changes in the vertical
      dimension of edentulous subjects.
AB  - The bite force and EMG activity of jaw closing muscles were studied at seven
      different vertical jaw positions around the occlusal vertical dimension (OVD) in
      10 edentulous subjects. When the masseteric EMG activity was maintained at
      constant values (40% and 20% of the maximum activity at the OVD), the bite force
      increased in proportion to increase of the vertical dimension. On the other hand,
      when the bite force was maintained at constant values (4 kg and 8 kg), the EMG
      activities of the jaw closing muscles decreased, with an increase of the vertical
      dimension. These results indicate that the OVD is not the position at which the
      most efficient exertion of the bite force is obtained.

PMID- 8736447
TI  - Posterior palatal seal adaptation: influence of a high expansion stone.
AB  - In this follow-up investigation, the ability of a new, high expansion stone to
      reduce acrylic resin denture base processing distortions was studied and compared
      with a previously reported investigation of bases processed on buff stone.
      Denture bases were processed by the continuous-injection and trial-pack
      techniques on flat vault palate casts and then trimmed and polished. Measurements
      were made at the posterior palatal border opening at 1 day and 1 week immersion
      in water (23 degrees C). Results showed that denture bases processed on high
      expansion stone had better posterior palatal seal adaptation compared with those
      processed on buff stone, independent of processing techniques.

PMID- 8736448
TI  - Analysis of composition and structure of hard autopolymerizing reline resins.
AB  - The authors investigated the composition and structure of six hard auto
      polymerizing reline resins. The chemical compositions, glass transition
      temperatures, molecular weights and particle size distributions of the powders,
      and the chemical compositions of the liquids were examined. The powder
      compositions were classified into three groups. The first group contained
      poly(methyl methacrylate). The second contained poly(ethyl methacrylate) and
      poly(methyl methacrylate/ethyl methacrylate) and the third contained poly(ethyl
      methacrylate). The average molecular weights of these powders was about 2 x
      10(5). The indexes of molecular weight dispersion suggested that all powders
      contained polymers that had a narrow molecular weight distribution. The particle
      size distribution of these powders was classified into two groups. The first
      group was mainly in the range of 50-100 microns and the second mainly between 20
      and 50 microns. The composition of the liquids was classified into three groups.
      The first group contained a monofunctional methacrylate monomer. The second
      contained a monofunctional methacrylate monomer and a plasticizer and the third
      contained monofunctional methacrylate monomers and cross-linking agents. The
      results of this experiment showed the differences in composition among the
      products. This will be useful for examining the relationship between the
      composition and mechanical properties of hard autopolymerizing reline resins.

PMID- 8736449
TI  - Effects of food/oral simulating fluids on microstructure and strength of dentine
      bonding agents.
AB  - This study evaluated the effect a food simulating solution, 75% v/v
      ethanol/water, and an artificial saliva, Moi-Stir, have on the microstructure and
      on the diametral tensile strength (DTS) of three dentine bonding agents (Tenure,
      Scotchbond Multi-Purpose and Optibond). The microstructure was examined by using
      a scanning electron microscope (SEM). The DTS data were analysed using ANOVA and
      the Tukey LSD test. The microstructural observations were compared with changes
      in DTS. The SEM observation revealed deterioration of all bonding agents due to
      conditioning in the solutions for 30 days. The different solutions appeared to
      cause different reactions in the bonding agents. However, these effects may be
      exaggerated due to the presence of an air-inhibited surface layer. Those
      conditioned in Moi-Stir showed swelling. The presence of filler particles in the
      Optibond bonding agent appears to decrease the deterioration resulting from
      soaking. Materials conditioned in ethanol exhibited both dissolution and
      thinning. Diametral samples of each bonding material were tested after being
      conditioned in the above-mentioned solutions for 1, 7, 14 and 30 days.
      Conditioning significantly decreased the DTS of all bonding agents, except
      Optibond in Moi-Stir. Filled Optibond maintained its DTS longer than did the two
      unfilled bonding agents. The decrease in DTS of all the ethanol-conditioned
      groups is a function of the square root of time (P < 0.001) and conforms to
      Fick's laws of diffusion. The filled Optibond showed a lower ethanol diffusivity
      (0.5 x 10(-5) cm2 s-1) than the other two unfilled bonding agent systems (average
      1.2 x 10(-5) cm2 s-1) (P < 0.05). The high ethanol diffusivities were thought to
      be due to the presence of HEMA, a hydrophilic resin, in the bonding agent. These
      results also suggest that solution uptake occurred through the resin matrix.
      Filler particles may therefore play an important role in weathering resistance of
      these materials to oral environment solutions. The physical appearance and
      strength of dentine bonding agents are significantly altered by exposure to oral
      environment solutions.

PMID- 8736450
TI  - Blood pressure in young adults with and without a paternal history of premature
      coronary heart disease in Europe: the EARS Study. European Arteriosclerosis
      Study.
AB  - OBJECTIVE: The European Arteriosclerosis Study (EARS) was designed to identify
      variables which discriminate subjects with a paternal history of premature
      coronary heart disease (CHD) from controls and to study the distribution of these
      variables across Europe. In this article we report on the blood pressure (BP)
      data. DESIGN: Comparison of young individuals (18 to 26 years) from 14 different
      European universities with and without paternal history of premature (before 55)
      myocardial infarction (MI). SUBJECTS AND METHODS: 1994 university students were
      recruited, 682 with a positive paternal history of premature MI (cases) and 1312
      age and sex-matched controls. Following a rigid fieldwork and analyses protocol,
      data on life style, BP, anthropometric and analytical measurements were obtained.
      RESULTS: Only diastolic BP in female patients was different between cases and
      controls (P < 0.05). A significantly higher prevalence of high BP personal
      history in male cases than in controls was observed (P < 0.02). BP means showed
      significant regional differences with higher values in the northern and middle
      European countries respect to southern regions (P < 0.0001). BP values were
      positively correlated to body mass index (BMI) and waist to hip (W/H) ratio, no
      correlations were observed with alcohol consumption in this age group. Tobacco
      showed a negative independent correlation with both systolic and diastolic BP (P
      < 0.0001). The use of contraceptive pills was associated with higher systolic (P
      < 0.0001) and diastolic (P < 0.05) BP levels. After adjustment for covariants,
      only weak correlations were observed between BP, lipids and apolipoproteins. Apo
      E showed a positive correlation with BP. Lp(a) and fibrinogen showed no
      significant regression coefficients with BP. Among cholesterylesters, oleic acid
      percentages were negatively correlated to BP values (mainly diastolic BP: P <
      0.001), while the correlation with linoleic acid was positive (P < 0.001).
      Fasting glucose levels showed an independent correlation with systolic BP (P <
      0.0001) in a multiple regression analysis. CONCLUSIONS: In the group with
      paternal history of premature MI, the higher prevalence of personal history of
      high BP in males and the higher diastolic BP values in females suggest that high
      BP could play a role in the elevated CHD risk of this group. Epidemiological
      observations on BP distribution and its relation with anthropometric and
      biochemical covariants in a young group of age from different European countries
      are reported.

PMID- 8736451
TI  - The significance and trend of hypertension related deaths in urban Sierra Leonean
      Africans.
AB  - In order to determine the impact and trend of hypertension related deaths in the
      overall mortality of urban Sierra Leoneans, a review of death certificate records
      in the capital Freetown over the period 1983-1992 was undertaken. A total of
      25119 consecutive records were examined to identify those with hypertension as a
      major or contributory cause of death. For the purpose of this study, hypertensive
      stroke, cardiac and renal deaths were selected as the main hypertension related
      disorders. Hypertension related deaths accounted for an average of 7.5% of all
      deaths and 13.7% of deaths in those aged 40 years and above between 1983 and
      1992. For the latter group, stroke deaths accounted for 5.2%, cardiac deaths for
      4.7%, and renal deaths for 0.8% of total mortality. There were more male
      hypertensive stroke deaths but when expressed as a percentage of the total
      deaths, no sex difference was noted. Hypertensive stroke deaths accounted for 7%
      of all deaths in the age group 50-69 years in females, while hypertensive cardiac
      deaths, caused 6% of deaths in the 60-69 year age group in both sexes.
      Hypertensive renal death was infrequently recorded being present mainly in the 40
      49 year age group predominantly in males. When all hypertension related deaths
      were considered together, their major impact was in the seventh decade in females
      and in the eighth decade in males accounting for approximately 20% and 16% of all
      deaths respectively. Hypertension related deaths appeared to show a steady
      increase over the 10 year study period. Hypertension is a significant cause of
      death particularly in elderly urban Sierra Leoneans in Freetown and deaths from
      hypertension may be increasing.

PMID- 8736452
TI  - Home monitoring of blood pressure: limited value in general practice.
AB  - To investigate the reliability of home blood pressure (HBP) measurement as it is
      generally used in practice, we studied 50 consecutive newly referred hypertensive
      patients that were measuring HBP for at least 6 months before referral. No
      specific instructions on the technique of HBP measurement were given to the
      patients. HBP was compared to clinic BP (CBP) by using daytime ambulatory BP
      (ABP) as a reference method. The technique of HBP measurement used by the
      patients was assessed on the basis of a detailed questionnaire and the accuracy
      of the devices was tested against a mercury column. There was no difference
      between the degree of similarity of ABP with HBP or CBP (mean value of
      discrepancies and correlation coefficients) for systolic BP (SBP) and little
      difference for diastolic BP (DBP). However, the variability of discrepancies
      between HBP and ABP was equal to the corresponding variability between CBP and
      ABP, indicating that HBP was not better predictor of ABP than CBP. Although
      patients measured HBP more frequently than generally recommended, poor
      standardisation of measurement and wrong technique were particularly common. In
      conclusion, in the present study HBP measurement offered no advantage over CBP in
      predicting ABP. The theoretical advantages of HBP may be partially offset by
      incorrect technique and less standardised conditions of measurement. Without
      patients education and regular maintenance of devices HBP offers no advantage
      over CBP and should not be used. (This article is based on data presented at the
      7th European Hypertension Society Meeting in Milan, June 1995).

PMID- 8736453
TI  - Association between electrocardiographic ischemic abnormalities and ischemic
      heart disease risk factors in a Japanese population.
AB  - This cross-sectional study was undertaken to investigate the association of
      electrocardiographic (ECG) ischemic abnormalities with ischemic heart disease
      (IHD) risk factors in a Japanese population. Resting ECGs of 1201 subjects (572
      men and 629 women, aged 30 to 89 years), were coded independently by two coders
      according to the Minnesota Code. Blood pressure (BP) was recorded using a
      standard sphygmomanometer, and non-fasting serum total cholesterol and high
      density lipoprotein cholesterol were measured. Codes 1.1 and 1.2 were classified
      as myocardial infarction and codes 1.3, 4.1-4.4, 5.1-5.3 and 7.1 were classified
      as ischemia. Prevalence of ECG with evidence of IHD (IHD ECG) was defined as
      myocardial infarction and ischemia together. Levels of risk factors were compared
      between subjects with IHD ECGs and those without IHD ECGs. Multiple logistic
      regression analysis was used to ascertain the associations between IHD ECG and
      risk factors. The prevalence of myocardial infarction in the total population was
      1.5% and 0.7% in men and women, respectively and the prevalence of IHD ECGs was
      10% and 11.3% in men and women, respectively. Systolic blood pressure (SBP) was
      consistently higher in subjects with IHD ECGs in the total population of both
      sexes (P < 0.001, P = 0.001 for men and women respectively). Diastolic blood
      pressure (DBP) was higher only in men with IHD ECGs (P = 0.002). In middle-aged
      men (aged 30-59 years), total cholesterol was considerably higher in subjects
      with IHD ECGs, although this relationship was statistically not significant. In
      multiple logistic regression analysis, SBP was independently associated with IHD
      ECGs in both sexes (P = 0.001). Associations between IHD ECGs with total
      cholesterol, alcohol intake and smoking were not statistically significant. This
      study showed that electro-cardiographic IHD evidences in Japanese are
      predominantly associated with blood pressure level in both sexes.

PMID- 8736454
TI  - Prison life and the blood pressure of the inmates of a developing community
      prison.
AB  - The blood pressure (BP) of the inmates of a developing community prison was
      assessed. The inmates of the all-male prison were interviewed as regards medical
      and diet history, alcohol and smoking habit, use of hard drugs, salt intake and
      duration of prison confinement and had their BP measured. Sixty-two low social
      class males were similarly assessed as controls. Eighty-one of the 84 inmates
      consented. Systolic BP (SBP) ranged from 80-150 mm Hg (mean 115.1 +/- 1.7) for
      prisoners and 80 to 140 mm Hg (mean 107.5 +/- 1.6) for controls (P < 0.05);
      diastolic BP (DBP) from 50-110 mm Hg (mean 74.1 +/- 1.3) and 45-90 mm Hg (mean
      68.8 +/- 1.6) respectively (P < 0.05). Twelve (14.8%) of the prisoners had DBP >
      or = 85 mm Hg compared to three (4.8%) of controls (P = 0.05). The prisoners have
      been in confinement for 1 to 790 days. Both SBP and DBP increased with duration
      of confinement (r = 0.26 P = 0.02 and 0.22 P = 0.057 respectively). The
      prevalence of "hard' drug abuse, cigarette smoking and alcohol consumption was
      quite high among prisoners (34.6%, 66.7% and 77.8% respectively). The study
      suggests that both SBP and DBP are higher in the prisoners compared to controls
      and appear to increase with duration of prison confinement. This might in part be
      related to certain stressful factors associated with prison life and possibly
      substance abuse.

PMID- 8736455
TI  - Relationships between blood pressure components, lipids and lipoproteins in
      normotensive men.
AB  - The aim of this study is to assess the relationships between pulse pressure (PP)
      mean arterial pressure (MAP), clinical and lipid parameters in normotensive men.
      One hundred and twenty-seven normotensive men aged 35-64 years from the French
      department of Haute-Garonne were analysed. Blood pressure (BP) was measured using
      a random zero device. Correlation analysis was performed using Pearson's
      coefficient. Variables significantly related to PP and MAP were then introduced
      in a stepwise multiple regression analysis. On univariate analysis, PP was
      significantly and positively related to total cholesterol, triglycerides, VLDL
      and LDL-cholesterol and apo B. MAP was positively related to age, body mass index
      (BMI), triglycerides and VLDL-cholesterol. Stepwise multiple regression analysis
      showed only apo B to be independently related to PP after adjustment for MAP.
      Also, after adjustment for PP, only BMI and VLDL-cholesterol were related to MAP.
      Hence, MAP is related to BMI and VLDL-cholesterol, which are a common feature of
      hyperinsulinism. PP is linked to apo B, an important proatherogenic factor. These
      biological parameters appear specific of steady and pulsatile components of BP.
      The relationship between PP and apo B suggests a possible link between lipids and
      arterial stiffness, and may partly explain the prognostic value of PP in
      myocardial infarction.

PMID- 8736456
TI  - On the determinants of the creatinine clearance: a population study.
AB  - The objective of this study was to define the normal urinary creatinine clearance
      and its determinants. The creatinine clearance was measured in both sexes in a
      large random Belgian population sample (BIRNH: Belgian interuniversity Research
      on Nutrition and Health) by measuring serum creatinine and the 24 h urinary
      creatinine excretion. At a mean age of 50.8 years in 2,075 men and 50.1 years in
      1,933 women the mean creatinine clearance was 101 +/- 30.5 and 86.9 +/- 25.8
      ml/min respectively. In multiple regression analysis the creatinine clearance in
      both sexes correlated negatively with age and positively with weight and 24 h
      urinary sodium, potassium, calcium and magnesium (all P < 0.0001). Total R2 was
      0.40 in men and 0.35 in women. After adjustment for age, height and weight no
      significant relationship exists between the 24 h urinary creatinine clearance and
      either systolic or diastolic blood pressure. Serum creatinine increased with age,
      more so in women, and was at all ages higher in men compared to women. The
      creatinine clearance decreased with age in both sexes. Our study demonstrates the
      existence of highly significant associations between urinary cations and the
      creatinine clearance, independent of total caloric intake.

PMID- 8736457
TI  - Influence of the arterial blood pressure and nonhemodynamic factors on regional
      arterial wall properties in moderate essential hypertension.
AB  - Structural and functional abnormalities may occur at the left ventricle and in
      different large arteries in essential hypertension. Noninvasive high resolution
      pulsed doppler echo-tracking technique allows calculation of regional arterial
      wall properties, which might be determined by either hemodynamic or non
      hemodynamic factors. Therefore we aimed to study regional arterial wall
      properties in three different vascular territories and examined whether
      hemodynamic and non-hemodynamic parameters were significantly associated to a
      specific vascular territory. In 30 patients (mean age 47 +/- 2 years) with newly
      diagnosed and untreated essential arterial hypertension, arterial wall properties
      were determined at the carotid (common, external and internal), femoral, and
      brachial artery using a noninvasive ultrasound wall movement detector system. The
      study parameters were arterial diameter, relative diameter change, arterial
      distensibility (DC) and cross-sectional compliance (CC) coefficient. On the day
      of the experiments office blood pressure (BP) was measured as well as an
      ambulatory 24 h BP profile performed on an outpatient basis. Blood samples were
      taken on the day of the vascular examination for the determination of plasma
      renin activity (PRA), aldosterone, intact (1-84) parathyroid hormone (PTH),
      insulin and plasma noradrenaline and adrenaline. Among the studied vascular
      territories, only DC and CC of the common carotid artery were significantly (P <
      0.01) correlated with office and ambulatory systolic BP. Intact PTH was
      significantly correlated with the diameter (r = 0.61, P = 0.005) and DC (r = 
      0.53, P = 0.01) of the internal carotid artery. Noradrenaline was inversely
      correlated with DC of the femoral artery (r = - 0.55, P < 0.01). All correlations
      remained significant after adjustment for age and body mass index as confounding
      variables. In conclusion, in mild to moderate arterial essential hypertension
      there is a heterogeneity of vascular wall properties and their relationship to BP
      and humoral factors between brachial, femoral and carotid (common, external and
      internal) arteries. Our findings might renew interest in the old concept of the
      'circulatory paradox'.

PMID- 8736458
TI  - Potential mechanisms by which nonsteroidal anti-inflammatory drugs elevate blood
      pressure: the role of endothelin-1.
AB  - To determine whether endothelin-1 (ET-1) contributes to hypertension associated
      with non-steroidal anti-inflammatory drug (NSAID) usage in healthy, elderly,
      normotensive individuals a randomised, double-blind, placebo-controlled,
      crossover trial of indomethacin was undertaken in 41 healthy, elderly individuals
      with stable normotension or controlled hypertension (blood pressure (BP) < or =
      160/90 mm Hg). The main outcome measures were systolic and diastolic BP, heart
      rate, cardiac output, weight, creatinine clearance, plasma renin activity,
      aldosterone, endothelin-1 and arginine vasopressin concentrations and 24 h
      urinary endothelin-1 and 6 keto prostaglandin F1 alpha outputs. Analysis of
      covariance was used to evaluate the effect of indomethacin on BP and related
      parameters. Indomethacin treatment for 1 month increased systolic (+/- s.e.m.:
      4.1 +/- 2.2 mm Hg; 95% confidence interval 0 to 8.3 mm Hg) and diastolic BP (2.7
      +/- 1.1 mm Hg; 0.4 to 4.9 mm Hg) without altering cardiac output (P = 0.59),
      implying an increase in total peripheral resistance. Indomethacin treatment
      produced a small increase in weight (1.4 +/- 0.4 kg; 0.6 to 2.2 kg), a small
      reduction in renal function (creatinine clearance: 6.8 +/- 1.8 mis/min; 3.3 to
      10.3 mis/min) but a significant (83%) increase in daily urinary endothelin-1
      production (13.1 +/- 3.4 ng/ml; 6.4 to 19.8 ng/ml) without altering plasma ET-1
      concentration, suggesting increased renal synthesis. In conclusion, renal
      paracrine effects of ET-1 may contribute to NSAID-induced blood pressure
      elevation in humans.

PMID- 8736459
TI  - Medium-term effects of betaxolol monotherapy and combination therapy with
      nitrendipine on lipoprotein and apolipoprotein metabolism in patients with mild
      to moderate essential hypertension.
AB  - The objective of this study was to assess the medium-term effects of betaxolol, a
      long-acting, lipid-soluble, cardioselective, beta-adrenergic antagonist, alone
      and in combination with nitrendipine on blood pressure (BP) and metabolism of
      lipid, lipoprotein and apolipoprotein in patients with mild to moderate
      hypertension. Forty-seven patients (21 men, 26 women, average age 54 years)
      participated in an open controlled clinical trial. After a 4-week washout period,
      all of the patients received betaxolol monotherapy at a dose of 5-10 mg daily for
      6 months (Phase I). From month 7 through month 12 (Phase II), half of the total
      patients (Group B, n = 23) with diastolic blood pressure (DBP) of 95 mm Hg or
      more at the end of Phase I were also given nitrendipine (10-20 mg, once daily),
      while the remaining patients (Group A, n = 24) continued to receive only
      betaxolol. Systolic blood pressure (SBP), DBP, and heart rate (HR) were monitored
      once monthly. Serum lipid profiles were measured at study entry and after 6 and
      12 months of therapy. Betaxolol significantly reduced SBP, DBP, and HR in both
      groups during Phase I, and the reductions in SBP and DBP were markedly less in
      Group B than in Group A. During Phase II, the additional reduction of SBP and DBP
      to levels similar to those in Group A was achieved by betaxolol in combination
      with nitrendipine, and HR was slightly but significantly increased. Betaxolol
      monotherapy reduced serum levels of high density lipoprotein cholesterol (HDL-C)
      and increased levels of triglyceride, apolipoprotein (apo) C-II and apo C-III.
      Combination therapy with betaxolol and nitrendipine increased serum apo A-I but
      did not affect other lipid profiles. Our results indicate that betaxolol is an
      effective antihypertensive drug which has a preferable effect on HR and HDL
      profiles when combined with nitrendipine.

PMID- 8736460
TI  - No deterioration of insulin secretion by the potassium channel opener pinacidil
      in essential hypertension.
AB  - Hypertension has been associated with hyperinsulinemia and insulin resistance.
      The elevations in plasma insulin are the apparent adaptation of the pancreatic
      beta cell to the resistance to insulin. Maintenance of normal insulin release is
      therefore of great importance for subjects with hypertension. The potassium
      channel opener pinacidil has antihypertensive properties. Pinacidil has been
      shown to inhibit Insulin release in vitro in isolated pancreatic beta cells. We
      therefore studied the acute effect of pinacidil on insulin secretion and insulin
      sensitivity in hypertensive and control subjects. The acute effect of pinacidil
      (25 mg, orally) on plasma insulin was studied during a hyperglycemic clamp (180
      min, blood glucose 10 mmol/L) in 10 healthy volunteers and in 10 non-obese
      hypertensive patients in a randomised, placebo controlled double blind study.
      Fasting plasma insulin levels were 54.8 +/- 10.9 and 51.1 +/- 8.8 pmol/L in the
      control group and statistically significantly higher in the hypertensive group:
      90.5 +/- 16.6 and 100.0 +/- 16.2 pmol/L (with and without pinacidil,
      respectively, both P < 0.02 vs control group). Plasma insulin levels rose to
      maximum levels of 246.7 +/- 44.6 and 267.2 +/- 56.2 pmol/L after 5 min in the
      control group (with and without pinacidil, respectively, NS) and to maximum
      levels of 248.9 +/- 37.3 and 238.0 +/- 39.1 pmol/L after 5 min in the
      hypertensive group (with and without pinacidil, respectively, NS). Areas under
      the insulin curve (AUCinsulin) of the first and second phase did not differ
      between the control and hypertensive group, with or without pinacidil. In the
      control and the hypertensive group separately no statistically significant effect
      of pinacidil on the mean glucose infusion rate/mean insulin level (M/I) ratio, a
      measure for insulin sensitivity, was shown. When both groups were taken together,
      an increase in the M/I ratio under the influence of pinacidil was found for the
      third hour of the clamp (P < 0.02). In conclusion, fasting insulin levels in the
      hypertensive subjects were significantly higher than in the control subjects. The
      potassium channel opener pinacidil did not influence insulin secretion in
      hypertensive patients and healthy controls. Pinacidil may have an enhancing
      effect on insulin sensitivity.

PMID- 8736461
TI  - Axis I-axis II interactions.

PMID- 8736462
TI  - Personality dimensions in the chronic fatigue syndrome: a comparison with
      multiple sclerosis and depression.
AB  - This study investigated the relative rates of personality disturbance in chronic
      fatigue syndrome (CFS). Individuals who met the CDC criteria for CFS were
      compared to two other fatiguing illness groups, mild multiple sclerosis and
      depression, as well as sedentary healthy controls. Subjects were administered a
      structured psychiatric interview to determine Axis I psychiatric disorders and
      two self-report instruments to assess Axis II personality disorders and the
      personality trait of neuroticism. The depressed group had significantly more
      personality disorders and elevated neuroticism scores compared with the other
      three groups. The CFS and MS subjects had intermediary personality scores which
      were significantly higher than healthy controls. The CFS group with concurrent
      depressive disorder (34% of the CFS group) was found to account for most of the
      personality pathology in the CFS sample. The results are discussed in the context
      of the relationship between personality variables and fatiguing illness.

PMID- 8736463
TI  - The Tridimensional Personality Questionnaire in depression: state versus trait
      issues.
AB  - The goal of our study was to examine the stability over time of the personality
      measures defined by Cloninger's Tridimensional Personality Questionnaire (TPQ) in
      patients with major depression. We conducted a retrospective chart review of 63
      outpatients who had participated in one of three double-blind antidepressant
      trials. All subjects had completed the TPQ upon entry and upon termination of the
      12-week trials. Statistically significant decrements in harm avoidance scores
      were observed in those subjects whose depression improved, regardless of gender
      or duration of presenting depressive episode. No significant changes were
      observed in the other two dimensions (novelty seeking and reward dependence).
      Nonresponders as a group had no statistically significant decreases in any TPQ
      dimension or subscales. While novelty seeking and reward dependence remain
      relatively independent of mood, harm avoidance appears to be a measure which is
      elevated during depressive states and which changes with improvement of
      depression. These findings are consistent with those of other investigators.

PMID- 8736464
TI  - Personality disorder in obsessive compulsive disorder: a controlled study.
AB  - In order to assess Axis II pathology in Obsessive Compulsive Disorder patients as
      compared to other anxiety disorder patients, the Personality Disorder Examination
      was administered to 258 anxiety disorder patients. In contrast to a number of
      recent reports, a low rate of personality disorder diagnoses were found in the
      OCD sample as well as the anxiety disorder control subjects. The findings of the
      current investigation are discussed in terms of state-trait confounding.

PMID- 8736465
TI  - Lack of effect of ECS on rat brain inositol monophosphatase activity and inositol
      levels and of i.c.v. inositol on ictal and post-ictal length.
AB  - Lithium (Li) has often been compared to ECT in therapeutic spectrum and
      mechanism. Inhibition of inositol monophosphatase and reduction of brain inositol
      are major mechanisms of Li action. Many Li effects in animals and humans are
      reversible by inositol. We therefore studied interactions of ECS and inositol.
      ECS in rats did not reduce brain inositol monophosphatase activity or brain
      inositol levels. Intracerebroventricular injection of 10 mg inositol, a dose that
      reverses Li effects, had no effect on seizure length or post-ictal length.

PMID- 8736466
TI  - Frequency of neuropathology in a brain bank from a long-term, domiciliary
      population.
AB  - Postmortem analysis of brain chemistry and anatomy in the study of psychiatric
      disorders has enjoyed renewed interest recently. There are myriad difficulties in
      establishing a brain bank, including proper diagnosis and confounding
      neuropathology. These difficulties may become more pronounced in a long-term
      domiciliary facility. In order to begin to address neuropathologic
      considerations, we performed neuropathological examinations on each patient
      included in our bank of 20 brains. Forty-five per cent of all patients had
      significant and unexpected neuropathology. Selection of patients to be included
      in postmortem studies requires careful screening to enhance accurate
      neuropathological assessment.

PMID- 8736467
TI  - Loading dose imipramine--new approach to pharmacotherapy of melancholic
      depression.
AB  - This study investigated the therapeutic efficacy of loading doses of imipramine
      hydrochloride and compared it with that of conventional gradually escalating dose
      regimen of the same drug in 16 melancholic depressives (DSM III-R), done in a
      comparative, randomized, double-blind research design. There were four males and
      four females in each group who were comparable on socio-demographic and clinical
      variables. The study group received the bolus doses of imipramine on two
      consecutive days and was free of any antidepressant treatment between day 3 and
      day 7 of the treatment period, whereas the control group received the
      conventional regime of gradual escalation of imipramine dose over a period of 7
      days. The results indicate that imipramine hydrochloride can relieve depression
      almost completely within 72 h, if given in high bolus doses, thus challenging the
      theory of lag period for antidepressant action as an inherent property of this
      drug. The study shows that the pulse loading dose was superior to a conventional
      dose regime with regard to both antidepressant efficacy and rapidity of onset of
      action. The various mechanisms possibly involved in such a dramatic improvement
      and its implications have been discussed.

PMID- 8736468
TI  - The effects of antecedent substance abuse on the development of first-episode
      psychotic mania.
AB  - We examined associations of antecedent drug and alcohol abuse with age of onset
      of bipolar disorder and the time to hospitalization in a sample of 59 patients
      presenting with their first episode of psychotic mania. Patients with first
      episode manic or mixed bipolar disorder with psychotic features were recruited
      from consecutive hospitalizations and evaluated using structured diagnostic
      instruments. Antecedent alcohol abuse was present in 12 patients (20%), and
      antecedent drug abuse in 19 (32%). Antecedent alcohol abuse was associated with a
      later age of onset of the bipolar disorder, although antecedent drug abuse was
      not associated with age of onset. Patients with antecedent drug or alcohol abuse
      required hospitalization sooner than those without. These preliminary findings
      suggest that patients with bipolar disorder and antecedent alcohol abuse may have
      a later onset of their affective illness, perhaps representing a subgroup of
      patients in whom previous alcohol abuse is necessary to precipitate an affective
      episode. Regardless, the presence of antecedent substance abuse leads to more
      rapid hospitalization in these patients. Our results should be considered
      preliminary, given the small sample size and the post-hoc design of the study.
      Additional prospective studies of patients with new onset bipolar disorder and
      antecedent substance abuse syndromes are needed to further clarify the complex
      relationships between substance abuse and bipolar disorder.

PMID- 8736469
TI  - The family metaphor applied to nursing home life.
AB  - The family metaphor was applied to data from participant observations of 18 lucid
      nursing home patients in order to highlight how nursing home life influenced
      their experience of health. The instrumental activities in the nursing home were
      more routinised and specialised than in a family, but usually care was observed
      to be tender, loving and diligent. Further analysis revealed many factors, which
      may combine to disturb self-esteem and prevent efforts towards further
      maturation: loss of continuity to earlier self, collectivisation of activities,
      extreme dependence, embarrassing situations, child role, and constantly mild
      behaviour from staff.

PMID- 8736470
TI  - Rural nurses' use of universal precautions in relation to perceived knowledge of
      patient's HIV status.
AB  - The increased incidence of AIDS in rural areas of the United States has called
      attention to the practice of universal precautions by rural nurses. The purpose
      of this research was to determine protective barrier use by 555 nurses living in
      rural counties in Pennsylvania and New York State and the effect on this use of
      their knowledge of their patients' HIV status. Findings suggest that nurses
      increased their use of protection if they knew their patients were HIV-positive.
      However, if they thought that their patients were HIV-negative or if they did not
      know their patients' HIV status, they did not always use adequate protection.
      Findings are discussed as they relate to the context of rural nursing practice.

PMID- 8736471
TI  - Effects of Orem-based nursing intervention on nutritional self-care of myocardial
      infarction patients.
AB  - The purpose of the study was to investigate the effect of nursing care based on
      Orem's nursing theory on nutritional self-care of myocardial infarction patients.
      Self-efficacy was explored as a disposition which may motivate behavioral change.
      One hundred and four subjects were randomly assigned to treatment or control
      groups. The nursing intervention, which took place during the first 6 weeks
      following hospital discharge, was effective in supporting healthy low-fat eating
      behavior. Nursing care influenced patients' self-care agency but lacked impact on
      self-efficacy for healthy eating.

PMID- 8736472
TI  - A young child's pain: how parents and nurses 'take care'.
AB  - A qualitative study was undertaken to describe how parents and nurses respond to
      hospitalized young children experiencing pain from surgical interventions.
      Participant observation was used to identify care behaviours and the care context
      within which the children experienced, and caregivers witnessed, post-operative
      pain. Interviews with parents, nurses, and children were also conducted during
      the observation periods and prior to discharge to augment the observational data.
      Care provided by parents included comfort measures and vigilant monitoring of the
      children's pain. Nurses primarily provided technical care, used limited pain
      assessment approaches, and were not able to adequately alleviate the children's
      pain. Factors, strategies, and feelings associated with these care behaviours are
      described. The most salient recommendations arising from these findings are that
      nurses: (a) be provided with education about pain assessment and management, and
      (b) be empowered by policies that allow them to sensitively and effectively
      respond to children in pain.

PMID- 8736473
TI  - Public perceptions of a health visitor.
AB  - This paper outlines the views of a random sample of 175 members of the public on
      the role and function of the health visitor. Those who had previous contact with
      a health visitor were more likely to know her employer but not necessarily her
      qualifications. They also had a greater knowledge of the type of clients a health
      visitor may see and the advice she is able to give. Although many people were
      aware of the health visitor's work in health promotion, very few would contact a
      health visitor for health advice, the vast majority choosing to see their GP.
      Health visitors should be aware of this and the way in which their profession is
      viewed by those whose health they aim to influence and may also consider a change
      of name and/or direction if the profession is to continue to develop and be more
      responsive to the needs of the 90s.

PMID- 8736474
TI  - Development of community nursing: analysis of the central services and practice
      dilemmas.
AB  - As examples of nurse practitioners in primary care, Swedish district nurses have
      been shown, in several studies, to respond well to the general pressure to
      achieve higher productivity in health care. Yet they have less frequently been
      involved in studies of the detailed content of the service they provide. To
      maintain total service quality, change should not be brought about only for the
      sake of efficacy. This study is divided into an analysis of the basic service
      provided in district nursing by identifying a typical interaction with a patient;
      and an analysis of the daily dilemmas district nurses experience, their
      consequences, and possible measures for change. For the consultation study, data
      were collected from 40 videorecordings of office-hour consultations by a rural
      district nurse. Regarding the dilemma situations, a critical incident
      questionnaire was returned by 153 district nurses in a Swedish country. The
      analyses showed that the district nurse practises in an area between self-care on
      the one hand, and the intersection of the different specialties in health care,
      on the other. Both the consultation study and the study of dilemmas in practice
      showed that the district nurse has to approach the health care organisation from
      a viewpoint close to that of the patient, which implies that she can, and has to,
      maintain an overview of the patient's total interaction with social institutions.
      This focal localisation of the shared care and co-ordination aspects constitutes
      a critical target for change and development efforts. The conclusions are that,
      first, the role of the district nurse/nurse practitioner as co-ordinator and
      advocate in patient-centred care could be considered in central health services
      policies and planning. Second, the content of the district nurses' daily work
      could be taken into account in the implementation of quality programs. These
      measures together can lead to an integration between today's theoretical nursing
      models and the dynamically changing structures of health care organisations.

PMID- 8736475
TI  - A study of health centers in Saudi Arabia.
AB  - Saudi Arabia is a developing country with a tremendous potential for growth and
      development. In an attempt to endorse Primary Health Care (PHC) concepts, it
      abolished all its former dispensaries and maternal and child health centers, and
      amalgamated their services into health centers that deliver PHC services. This
      expansion in centers development created a need for evaluation to assess the
      extent at which the new objectives are being achieved. The purpose of this study
      was to evaluate the resources available in three large health centers in Saudi
      Arabia, and determine consumers' satisfaction with the services provided. The
      study was conducted in the City of Riyadh. Three centers were chosen purposefully
      and the consumers of the respective centers were interviewed as to their
      satisfaction with the services provided. The results show that there was a
      discrepancy between the findings obtained from the centers' resources evaluation
      and those derived from the satisfaction portion. It is recommended that the Saudi
      Ministry of Health would upgrade its centers' resources, and that more studies
      would be conducted in the other centers of the country.

PMID- 8736476
TI  - The question of knowledge in district nursing.
AB  - This paper focuses on the development of the experiential knowledge base in
      district nursing with reference to changes in professional preparation for
      district nurses and to a research study conducted by the author during the 1970s.
      The process of conducting the research showed that an exclusive focus on activity
      fails to capture the range and depth of nursing care in the home. Schon's concept
      of professional artistry is employed as an interpretive framework to consider
      some of the study findings and with reference to more recent research studies the
      author concludes that while it has always been central to skilled nursing,
      professional artistry has remained hidden. The problems confronting academics and
      practitioners in articulating such knowledge are explored together with the
      possible consequences of continued failure to address this issue. These
      difficulties are discussed in the context of the current changes in the National
      Health Service with particular reference to the introduction of grade mix in
      community nursing. The paper concludes by arguing that a better understanding of
      the district nurse's knowledge base must be vigorously pursued.

PMID- 8736477
TI  - Diabetic adolescents' compliance with health regimens and associated factors.
AB  - Fifty-one young diabetics responded to a questionnaire concerning compliance and
      were interviewed on two topics: the meaning of care to the subjects and the
      nature of their support system. Diabetes control was measured by glycosylated
      haemoglobin (GHB). Interview data were analysed by continuous comparative
      analyses. The categories obtained were quantified and the relationship between
      variables analysed by cross tabulation, chi-square test and discriminant
      analysis. Those who responded with a good compliance showed good control of
      diabetes as indicated by GHB values and reported sufficient energy and will-power
      to implement the health regimens. Those young people who reported that they had
      sufficient energy and will-power considered care important, received
      encouragement, felt that care brings well-being and had no fears of
      complications.

PMID- 8736478
TI  - A comparison of two methods of measuring fatigue in patients on chronic
      haemodialysis: visual analogue vs Likert scale.
AB  - The study compared level of fatigue measured by two self-report instruments in 43
      patients on chronic haemodialysis. The two fatigue measures were the multi-item
      fatigue subscale of the Profile of Mood States (POMS) and a single-item visual
      analogue scale (VAS). There was a significant relationship between the two
      measures (r = 0.80); however, the shared variance was only 64%. Males and
      females, as well as subjects of different ages, responded to the two scales in
      different ways. Nurses need to know that different tools may give different
      results, even when the same concept, that is fatigue, is being measured in the
      same subjects at the same time.

PMID- 8736479
TI  - Oestrogens and progestins and breast cancer risk in post-menopausal women.

PMID- 8736480
TI  - Hormone replacement therapy and the breast cancer issue.

PMID- 8736481
TI  - The use of oestrogens and progestin and the risk of breast cancer in post
      menopausal women. G.A. Colditz et al. N. Engl. J. Med. 1995; 332: 1589-93.

PMID- 8736482
TI  - Critical review of the article by Colditz et al. on 'The use of estrogens and
      progestins and the risk of breast cancer in postmenopausal women' published in
      the N.E.J.M. 1995, 332: 1589.

PMID- 8736483
TI  - Does post-menopausal hormone-replacement therapy increase risk for breast cancer?
      A perspective on the findings of the Nurses' Health Study.

PMID- 8736484
TI  - Pharmacological implications of inward rectifier K+ channels regulation by
      cytoplasmic polyamines.
AB  - The powerful combination of molecular biology and electrophysiology has allowed
      extraordinary progress in the field of ion channel structure-function. In fact,
      only 10 years have passed since the first amino acid sequence of a voltage
      dependent ion channel, the Na+ channel, was deduced [1], and already the
      structural domains involved in ion channel permeation, block and gating have been
      identified in many channel types. Despite this progress, in most cases the
      correlation between specific domains and ion channel function is still
      speculative at present, due to the absence of direct structural information [2].
      In this review we will describe recent progress in the field of structure
      function of one class of K+ channels, the inward rectifiers (IRKs). In
      particular, we will review the sequences of structure-function experiments which
      have led to the discovery of a novel regulation of IRKs by cytoplasmic organic
      polycationic substances like polyamines (PAs). This discovery represents a
      paradigm for how structure-function information has preceded and made possible
      the identification of physiological mechanisms of ion channel regulation. Owing
      to the important role played by IRKs in the regulation of resting membrane
      potential, a major determinant of cellular transport and volume [3], and to the
      established link between PAs and cell growth and division, the direct regulation
      of IRKs by PAs assumes a critical importance for the pharmacological control of
      cell growth and neoplastic transformation.

PMID- 8736485
TI  - The heterogeneity of vesicular acetylcholine storage in cholinergic nerve
      terminals.
AB  - The vesicular hypothesis of quantal acetylcholine release describes the process
      by which discrete packages (or quanta) of the transmitter are released from nerve
      terminals through the exocytosis of the content of synaptic vesicles. However,
      cholinergic synaptic vesicles can no longer be vaguely regarded as simple
      membrane bound 'sacks' of the transmitter. Modern molecular, biochemical,
      morphological and electrophysiological research has revealed them to be complex
      cellular structures with a heterogeneous mixture of functions. Thus, not all
      synaptic vesicle populations are formed under the same circumstances and there
      are variations in the releasability of synaptic vesicle populations. This review
      briefly outlines some of the experimental research that has lead to our current
      thinking on the heterogeneity of vesicular acetylcholine storage in cholinergic
      nerve terminals. In addition, a model for vesicular acetylcholine storage and
      release is presented that attempts to accommodate many of the modern ideas
      concerning cholinergic synaptic vesicle function and interaction.

PMID- 8736486
TI  - Effects of different sampling strategies on predictions of blood cyclosporine
      concentrations in haematological patients with multidrug resistance by Bayesian
      and non-linear least squares methods.
AB  - The Bayesian method (BM) can use previous information for the optimization of
      dosage regimen. However, Bayes' law remains true when the parameters are obtained
      from the infinite population. Therefore a bias might exist in the previous
      information and affect BM predictive performance. To overcome this shortcoming,
      the blood drug concentration of a patient can be used to individualize his
      pharmacokinetic parameters. Until now, at least two sampling strategies, i.e.
      steady-state and non-steady-state sampling strategies, have been developed to
      individualize and predict blood drug concentration. In the present study we used
      five sampling strategies: (1) all samples; (2) post-infusion samples; (3) during
      infusion samples; (4) samples within 95% confidence interval/interquartile range
      of a steady-state concentration; (5) the sample of the mean/median at the mid
      time-point of a steady-state to individualize and predict blood cyclosporine
      concentrations in haematological patients with multidrug resistance. We
      investigated the effects of different sampling strategies on BM and the nonlinear
      least squared method (NLLSM) predictive performances. The results showed that BM
      predictive performance was better than NLLSM. But the results did not prove that
      the steady-state sampling strategies were superior to the non-steady-state ones.

PMID- 8736487
TI  - Cardiac and renal endothelin-1 binding sites in streptozotocin-induced diabetic
      rats.
AB  - The aim of this work was to study cardiac and renal endothelin binding sites
      during the progression of diabetes. Male Crl:CD (BR) rats were made diabetic by
      injection of streptozotocin (STZ, 45 mg kg-1 i.v.). Only rats with a glycaemia of
      500 mg per 100 ml or higher, were used. The hearts were taken at 2, 4 or 6 weeks
      and kidneys at 2 and 6 weeks, after diabetes induction, for binding studies. In
      the heart, the number of Et-1 binding sites was significantly increased 2 weeks
      after STZ-induction of diabetes (449 +/- 13 vs. 345 +/- 18 fmol (mg protein) -1,
      in controls; p < 0.05) without modification of KD value (104 +/- 5 vs 101 +/- 7
      pM). Comparable results were obtained 4 and 6 weeks after STZ-induction. In the
      kidney both the parameters were unchanged at all the times tested. IN CONCLUSION:
      a specific increase in cardiac Et-1 binding sites, without change in affinity of
      the peptide, was found 2, 4 and 6 weeks after diabetes induction; while renal Et
      1 binding sites were not modified.

PMID- 8736488
TI  - Radical scavenger activity of bendazac, an anticataract non-steroidal anti
      inflammatory agent.
AB  - Oxidative damage to lens components is associated with cataract formation and
      reactive oxygen species (ROS) overproduction at inflammation sites is thought to
      lead to the development of inflammatory disorders. Bendazac is a non-steroidal
      anti-inflammatory drug able to delay the cataractogenic process. Aim of the
      present study is to characterize, both chemically and biologically, the activity
      of this anticataract agent as a radical scavenger. Bendazac has been shown to be
      a strong reacting substrate in a chemical oxidizing system, which mimics a
      physiological pathway of hydroxy radical generation. In the Fenton-Cier reaction
      the drug rapidly forms a mixture of hydroxylated derivatives, among which 5
      hydroxybendazac, bendazac's main metabolite, being a hydroxy radical scavenger
      itself. Moreover, by means of a rapid and sensitive flow cytometric method able
      to determine reactive oxygen intermediate production, bendazac and its 5-hydroxy
      derivative were shown to inhibit oxidative burst activation in polymorphonuclear
      neutrophil leukocytes (PMNLs).

PMID- 8736489
TI  - Effects of hypoxia on enzyme activities in skeletal muscle of rats of different
      ages. An attempt at pharmacological treatment.
AB  - The activities of enzymes related to energy metabolism in the gastrocnemius and
      soleus muscles in young-adult (4 months), mature (12 months) and senescent (24
      months) rats were compared after 72 h of continuous exposure to normobaric
      hypoxia or normoxia after alpha-adrenergic antagonist nicergoline or saline
      solution had been given intraperitoneally for 30 consecutive days. The maximum
      rates (Vmax) of the following enzyme activities in the crude extract and/or the
      mitochondrial fraction of each muscle specimen were evaluated: (1) for the
      anaerobic glycolytic pathway: hexokinase, phosphofructokinase, pyruvate kinase
      and lactate dehydrogenase; (2) for the tricarboxylic acid cycle; citrate synthase
      and malate dehydrogenase; (3) for the electron transfer chain; cytochrome
      oxidase; and (4) for the NAD+/NADH redox state: total NADH cytochrome c
      reductase. The significant differences between the enzyme activities at different
      ages or under different experimental conditions in the two tissue preparations of
      the two muscles were determined by ANOVA. MCA and ETA were used to evaluate the
      net effects of the experimental conditions. Ageing did not seem to affect the
      soleus and gastrocnemius muscles in the same way. Changes were seen only in the
      glycolytic pathway enzymes in the crude extract from the gastrocnemius muscle. In
      the soleus muscle changes in enzyme activities as a function of ageing were also
      found in the mitochondrial fraction. We also found that hypoxia caused greater
      changes in 12-month-old rats than in those of other ages (especially in the
      enzyme activities of the gastrocnemius muscle). Finally out data show that only
      in certain cases was the pharmacological treatment able to modify the influence
      of hypoxic conditions on the levels of enzyme activities, regardless of the age
      of animals.

PMID- 8736490
TI  - Protective actions of L-carnitine and acetyl-L-carnitine on the neurotoxicity
      evoked by mitochondrial uncoupling or inhibitors.
AB  - The mechanism for the pathological increase in cell death in various disease
      states e.g. HIV immunodefficiency or even ageing or Alzheimer's disease, occurs
      by complex and as yet undefined mechanism(s) related to immunological,
      virological or biochemical disturbances (i.e. energy depletion, oxidative stress,
      increased protein degradation). We have studied mitochondrial uncoupling or
      inhibitor toxicity on neurones at the cellular level and at the mitochondrial
      level using rhodamine (Rh123) and 10-nonylacridine orange (NAO) fluorescence with
      confocal microscopy. Blockade of the mitochondrial chain complexes at various
      points was studied. The possible protective effects of the compound L-carnitine,
      which plays a central role in mitochondrial function, was tested in this form of
      neurotoxicity. It appears that L-carnitine and its acetylated form, acetyl-L
      carnitine, can attenuate the cell damage, as assessed by lactate dehydrogenase
      (LDH) release, evoked by the uncoupler, p-(trifluoromethoxy)phenylhdyrazone
      (FCCP), or by the inhibitors, 3-nitropropionic acid (3-NPA) or rotenone. Further,
      the FCCP-induced inhibition of Rh123 uptake was antagonized by the preincubation
      of cells with L-carnitine. Since such neurotoxic mechanisms may be operating in
      the various pathological forms of myotoxicity and neurotoxicity, these
      observations suggest potential for a therapeutic approach.

PMID- 8736491
TI  - A databank (3D-ali) collecting related protein sequences and structures.

PMID- 8736493
TI  - Analysis of protein conformational characteristics related to thermostability.
AB  - The thermal stability of proteins was studied, 195 single amino acid residue
      replacements reported elsewhere being analysed for several protein conformational
      characteristics: type of residue replacement; conservative versus nonconservative
      substitution; replacement being in a homologous stretch of amino acid residues;
      change in hydrogen bond, van der Waals and secondary structure propensities;
      solvent-accessible versus inaccessible replacement; type of secondary structure
      involved in the substitution; the physico-chemical characteristics to which the
      thermostability enhancement can be attributed; and the relationship of the
      replacement site to the folding intermediates of the protein, when known. From
      the above analyses, some general rules arise which suggest where amino acid
      substitutions can be made to enhance protein thermostability: substitutions are
      conservative according to the Dayhoff matrix; mainly occur on conserved stretches
      of residues; preferentially occur on solvent-accessible residues; maintain or
      enhance the secondary structure propensity upon substitution; contribute to
      neutralize the dipole moment of the caps of helices and strands; and tend to
      increase the number of potential hydrogen bonding or van der Waals contacts or
      improve hydrophobic packing.

PMID- 8736492
TI  - Recognition of transmembrane alpha-helical segments with environmental profiles.
AB  - A method for assessing the environmental properties of membrane-spanning alpha
      helical peptides in proteins has been proposed. The algorithm employs a set of
      environmental preference parameters derived for amino acid residues based on the
      analysis of the 3-D structures of membrane domains in bacteriorhodopsin and
      photoreaction centers Rhodopseudomonas viridis and Rhodobacter sphaeroides. The
      resulting 3-D-1-D scores for transmembrane segments are significantly different
      from those derived for alpha-helices in globular proteins. The parameters
      obtained have been used to construct environmental profiles for membrane alpha
      helices in bacteriorhodopsin and photoreaction centers. The profiles successfully
      recognize their own sequences in several specially designed large databases. The
      method has been applied to several membrane proteins with unknown spatial
      structures. Most of their membrane-spanning peptides were efficiently recognized
      by the profiles. The predicted environment of the residues in the membrane
      segments fits the experimental data well. The approach is independent of any
      homology data and can be employed to delineate the membrane segments of a protein
      with environmental characteristics close to those of bacteriorhodopsin and
      photoreaction centers. The alignment of these segments with the reference
      profiles provides a considerable amount of data about their lipid and protein
      exposure.

PMID- 8736494
TI  - Free energy calculations of the mutation of Ile96-->Ala in barnase: contributions
      to the difference in stability.
AB  - Free energy calculations were carried out to determine the relative unfolding
      free energy of the Ile96 wild type and Ala96 mutant barnases. The total
      calculated free energies suggest that substitution of Ile96 with Ala destabilizes
      barnase by 3.9 kcal/mol, which is in good agreement with the independently
      determined experimental values of 4.0 and 3.3 kcal/mol and a previous simulation.
      However, a decomposition of the free energy finds the dominant contributions to
      this free energy arising from the noncovalent interactions between the perturbed
      group and distant residues of barnase in the sequence and water molecules and
      only a very small contribution from covalent interactions. This is in contrast to
      the previous simulation, using the dual topology methodology, which produced a
      decomposition with an approximately 60% free energy contribution from changes in
      covalent interactions. The use of the single topology employed in the present
      calculations and the dual topology employed in the previous study are analyzed in
      order to understand the contrast between the present results and the results of
      the previous study.

PMID- 8736495
TI  - Locating the unpaired cysteine of tissue-type plasminogen activator.
AB  - Variants of tissue-type plasminogen activator (t-PA) were constructed with
      selected cysteines replaced by alanine to evaluate the role of an unpaired
      cysteine, which has been presumed to be in the growth factor module. C75A, C83A,
      C84A and CC83-84AA variants of t-PA were expressed transiently in human embryonic
      kidney cells. The biochemical properties of these variants provided experimental
      evidence to identify the unpaired cysteine in t-PA. Assays of amidolytic
      activity, plasminogen activation (in the presence or absence of fibrinogen or
      fibrin), plasma clot lysis, fibrin binding, clearance in mice, and interaction
      with a panel of monoclonal antibodies were performed as the basis for comparing
      these variants with wild-type t-PA. In all assays, C83A t-PA was biochemically
      equivalent to wild-type t-PA. C75A t-PA, C84A t-PA and CC83-84AA t-PA variants
      exhibited reduced activities in a variety of functional assays. These variants
      displayed two-to threefold lower activity in fibrinogen or fibrin stimulated
      plasminogen activation, and fivefold reduced plasma clot lysis activity compared
      with that of wild-type t-PA. The affinity of C75A t-PA and C84A t-PA for fibrin
      was decreased more than two orders of magnitude compared with C83A t-PA or wild
      type t-PA. Plasma clearance of C75A t-PA and C84A t-PA was reduced 2-fold in
      mice. The C75A, C84A and CC83-84AA variants displayed significantly decreased
      reactivity with anti-tPA monoclonal antibodies specific for finger/growth factor
      domain epitopes. These data are consistent with a disulfide linkage of Cys75 with
      Cys84 and that Cys83 exists as an unpaired sulfhydryl. The significance of the
      unpaired cysteine is as yet undetermined since C83A t-PA and wild-type t-PA are
      functionally equivalent.

PMID- 8736496
TI  - Engineering the aggregation properties of dodecameric glutamine synthetase: a
      single amino acid substitution controls 'salting out'.
AB  - Escherichia coli glutamine synthetase (GS) is a dodecamer of identical subunits
      which are arranged as two face-to-face hexameric rings. In the presence of 10%
      ammonium sulfate, wild type GS exhibits a pH-dependent "salting out' with a pKa
      of 4.51. Electron micrographs indicate that the pH-dependent aggregation
      corresponds to a highly specific self-assembly of GS tubules, which result from
      stacking of individual dodecamers. This stacking of dodecamers is similar to the
      metal ion-induced GS tubule formation previously described. Site-directed
      mutagenesis experiments indicate that the N-terminal helix of each subunit is
      involved in the salting out reaction, as it is in the metal-induced stacking. A
      single substitution of alanine for His4 completely abolishes the (NH4)2SO4
      induced aggregation. However, the H4C mutant protein does nearly completely
      precipitate under the same salting out conditions. Mutations at other residues
      within the helix have no effect on the stacking reaction. Differential catalytic
      activity of unadenylylated GS versus adenylylated GS has been used to determine
      whether wild type dodecamers "complement' the H4A mutant in the stacking
      reaction. The complementation experiments indicate that His4 residues on both
      sides of the dodecamer-dodecamer interfaces are not absolutely required for
      salting out, although the wild type dodecamers clearly stack preferentially with
      other wild type dodecamers. Approximately 20% of the protein precipitated from
      the mixtures containing the wild type GS and the H4A mutant is the mutant. The
      implications of these results for protein engineering are discussed.

PMID- 8736498
TI  - Synthetic collagen-like domain derived from the macrophage scavenger receptor
      binds acetylated low-density lipoprotein in vitro.
AB  - The bovine macrophage scavenger receptor is a 70 kDa membrane protein that is
      trimerized on the macrophage cell surface. The receptor binds modified low
      density lipoproteins (LDL). The core binding site is located within 22 residues
      at the C-terminus of the collagen-like domain of the receptor. The Lys residue at
      position 337 plays an important role in ligand binding. Here, the collagen-like
      domain was constructed using a peptide architecture technique, in which three
      collagenous peptide chains were crosslinked at their N-termini. The crosslinked
      peptide showed a collagen-like structure by circular dichroism and existed mainly
      in a monomeric triple helical form as shown by gel exclusion chromatography. The
      triple-stranded peptide was demonstrated to bind acetylated LDL (Ac-LDL) using
      regions derived from Gly323 to Lys340 of the natural bovine scavenger receptor.
      However, a single-stranded peptide with the same amino acid sequence did not bind
      Ac-LDL. Furthermore, a triple-stranded mutated peptide in which Lys corresponding
      to Lys337 in the mother protein was substituted with Ala showed no binding
      activity to Ac-LDL. These results, taken together, indicate that the synthetic
      collagen-like peptide has a similar structure to the binding site in the
      scavenger receptor, and support the view that the collagen-like domain of the
      natural scavenger receptor recognizes Ac-LDL.

PMID- 8736499
TI  - On the choice of reference mutant states in the application of the double-mutant
      cycle method.
AB  - Pairwise interactions in proteins can be detected and, in certain circumstances,
      their strength measured by applying the method of double-mutant cycles. Such
      cycles comprise wild type protein, two single mutants and the corresponding
      double mutant. The analysis of double-mutant cycles is most straightforward when
      the mutations are to alanine since interactions are mostly removed without new
      interactions being formed. Here, 'not-to-alanine' double-mutant cycles are
      analysed. It is shown that a 'not-to-alanine' double-mutant cycle can be
      decomposed into four double-mutant cycles with mutations only to alanine. The
      coupling energy corresponding to the 'not-to-alanine' double-mutant cycle is
      expressed as a function of the coupling energies of these four cycles.

PMID- 8736497
TI  - Specific killing of lymphoma cells by cytotoxic T-cells mediated by a bispecific
      diabody.
AB  - Antibody fragments produced by bacterial fermentation lack natural effector
      functions. Bispecific antibody fragments, however, can be endowed with effector
      functions, for example cell-mediated killing, by binding to and retargeting of
      cytotoxic cells. Diabodies are a class of engineered antibody fragments with two
      antigen binding sites, consisting of two associated chains; each chain consists
      of heavy and light chain variable domains linked by a short polypeptide linker.
      In contrast to IgG, or other antibody fragments in which the two binding sites
      can take up a range of orientations and spacings, the diabody structure is more
      rigid and compact, with the two binding sites separated by 65 lA (less than half
      the distance in IgG). To establish whether diabodies could also be used in cell
      mediated killing, we have explored the use of a bispecific diabody binding to an
      idiotypic marker on mouse B-cell lymphoma (BCL-1) and to mouse CD3. The
      bispecific diabody activated naive T-cells and also mediated the specific killing
      of the lymphoma cells by cytotoxic T-cells. The diabody was less active in T-cell
      activation but 10-fold more active (w/v) in killing than an analogous bispecific
      IgG.

PMID- 8736500
TI  - Concurrent bovine viral diarrhoea virus and Salmonella typhimurium DT104
      infection in a group of pregnant dairy heifers.
AB  - Two days after being imported into the United Kingdom one of a group of 30
      pregnant dairy heifers showed clinical signs of bovine viral diarrhoea virus
      (BVDV) infection and subsequently died. Before it died the heifer was BVDV
      antigen-positive and antibody-negative. The gross post mortem findings were
      suggestive of mucosal disease but in addition to noncytopathic BVD virus,
      Salmonella typhimurium DT104 was cultured from tissues and gut contents. The
      other heifers were screened for S typhimurium by culturing faeces, and serology
      showed that 13 (45 per cent) of the group seroconverted to BVDV in the three
      weeks between samplings and the remainder were seropositive, indicating previous
      exposure. During this period four heifers showed clinical signs of acute BVDV
      infection but recovered uneventfully. Four animals (14 per cent) were positive
      for S typhimurium DT104 on faecal culture, and three of these excretors
      concurrently seroconverted to BVDV. Of the 29 heifers remaining in the group, one
      aborted in late gestation, 26 bore live calves and two delivered stillborn
      calves. Pre-colostral blood samples from the calves showed that their dams' pre
      existing antibody titres correlated well with in utero fetal protection. In non
      immune dams, exposure to BVDV between 69 and 120 days of gestation led to the
      birth of live persistently viraemic calves. Infection between 120 and 140 days of
      gestation led to the birth of live calves with evidence of congenital damage to
      the central nervous system, and infection later than 140 days of gestation led to
      the birth of live, normal calves with high pre-colostral antibody titres to BVDV.
      One calf which sucked colostrum was antibody and virus antigen-positive when
      sampled at 12 hours old but regular blood sampling failed to detect viraemia
      again until the calf was seven weeks old when it became persistently viraemic.

PMID- 8736501
TI  - Clinical evaluation of in-feed zinc bacitracin for the control of porcine
      intestinal adenomatosis in growing/fattening pigs.
AB  - This field trial was designed to investigate whether the incorporation of zinc
      bacitracin into pig feed would prevent porcine intestinal adenomatosis. Two
      hundred-and-eighty-eight weaned pigs on a farm with a previous history of the
      disease were divided into 16 pens of 18 pigs. Two dietary regimens of zinc
      bacitracin were tested: from weaning up to 100 days of age, either 300 or 200 ppm
      zinc bacitracin were incorporated; from 100 to 125 days of age, either 200 or 100
      ppm zinc bacitracin were added; and from 125 to 156 days of age (slaughter),
      either 100 or 50 ppm zinc bacitracin were added. The results were compared with a
      positive control group which received 60, 60 and 30 ppm salinomycin during the
      same periods, and with a negative control group which received no antibacterial
      and/or performance enhancer. The mortality, diarrhoea scores, average daily
      weight gains, average daily feed intakes and feed conversion ratios of the pigs
      were assessed. At slaughter, samples of ileum were taken from eight randomly
      selected pigs per group for bacteriological and histopathological examinations.
      The three treated groups all performed better than the control group, and the
      group receiving the high dose regimen of zinc bacitracin performed significantly
      better than the groups receiving the low dose of zinc bacitracin or salinomycin.

PMID- 8736502
TI  - Epidural lipomatosis in a six-year-old dachshund.
AB  - A six-year-old female dachshund was examined because of intermittent lameness in
      its left pelvic limb and periodic back pain. Myelography, epidurography and
      computed tomography (CT) revealed a dorsal displacement of the dural sac in the
      lumbosacral region caused by a soft tissue mass which had the specific density of
      fat. The mass was removed via a dorsal laminectomy in the lumbosacral area and a
      histological examination confirmed that it was adipose tissue. The clinical signs
      resolved after the surgery and a follow-up CT five months later showed no
      evidence of compression of the dural sac. The diagnosis of epidural lipomatosis
      in this dog was based on the clinical findings, the results of diagnostic
      imaging, and the surgical and histological findings, all of which revealed many
      similarities with epidural lipomatosis in man.

PMID- 8736503
TI  - Comparison of isolates of canine parvovirus by monoclonal antibody and
      restriction enzyme analysis.

PMID- 8736504
TI  - Surgical correction of a canine preputial deformity.

PMID- 8736505
TI  - A case of true hermaphroditism in a sheep.

PMID- 8736506
TI  - Acute pleuropneumonia in Barbary sheep (Amnotragus lervia) associated with
      Chromobacterium violaceum.

PMID- 8736507
TI  - Dispensing of medicines and professional fees.

PMID- 8736508
TI  - Idiopathic moult in parrots.

PMID- 8736509
TI  - RCP guidelines: the use of radioiodine in the management of hyperthyroidism.

PMID- 8736510
TI  - Quality of care: identification and quantification of the process of care among
      children undergoing nuclear medicine studies.
AB  - The aim of this study was to define indices which could be used to assess the
      quality of care of children undergoing an examination requiring intravenous
      (i.v.) access in an integrated department of radiology and to see if these
      indices could be quantified. A prospective study of all patients requiring an
      i.v. injection for a nuclear medicine examination (NME) over a period of 8 weeks
      was undertaken. The following indices were assessed: the waiting time of the
      patients in the department for a NME, the use of EMLA (a local anaesthetic
      cream), use of sedation, and number of attempts to achieve i.v. access. The 219
      males and 174 females had a median age of 46 months. EMLA was applied to 298
      children. The median times from arrival to the application of EMLA was 5 min,
      between EMLA to the injection 59 min, and between arrival to injection 65 min.
      Seventeen children had sedation. Intravenous access was achieved on the first
      attempt in 76.7% of cases and three or more attempts were made in 8.5% of cases.
      Successful injections were made in 91.5% of the children; 8.2% had partial
      extravasation of the radio-isotope at the injection site and in one patient the
      examination was abandoned due to an inability of gaining i.v. access. This study
      has identified and quantified indices to measure the quality of care for children
      undergoing an i.v. injection in an imaging department. Baseline values have been
      established for i.v. access, sedation and waiting times in the radiology
      department for various NMEs. Undertaking multiple imaging procedures on the same
      day requires careful scheduling and complex organization.

PMID- 8736511
TI  - The virtual gamma camera room.
AB  - The installation of a gamma camera is time-consuming and costly and, once
      installed, the camera position is unlikely to be altered during its working life.
      Poor choice of camera position therefore has long-term consequences. Additional
      equipment such as collimators and carts, the operator's workstation and wall
      mounted display monitors must also be situated to maximize access and ease of
      use. The layout of a gamma camera room can be optimized prior to installation by
      creating a virtual environment. Super-Scape VRT software running on an upgraded
      486 PC microprocessor was used to create a 'virtual camera room'. The simulation
      included an operator's viewpoint and a controlled tour of the room. Equipment
      could be repositioned as required, allowing potential problems to be identified
      at the design stage. Access for bed-ridden patients, operator ergonomics,
      operator and patient visibility were addressed. The display can also be used for
      patient education. Creation of a virtual environment is a valuable tool which
      allows different camera systems to be compared interactively in terms of
      dimensions, extent of movement and use of a defined space. Such a system also has
      applications in radiopharmacy design and simulation.

PMID- 8736512
TI  - Comparison of 201Tl, 99Tcm-MIBI and 131I imaging in the follow-up of patients
      with well-differentiated thyroid carcinoma.
AB  - Problems stemming from the withdrawal of TSH suppressing doses of T4 or T3 and
      false-negative studies associated with 131I scintigraphy have justified the
      search for other radionuclides in the follow-up of patients with well
      differentiated thyroid carcinoma. Although 201Tl and 99Tcm-MIBI (MIBI) have been
      suggested as alternatives, their role in the detection of residual and recurrent
      disease has yet to be established. We therefore studied 36 patients who had
      undergone total or near total thyroidectomy for well-differentiated thyroid
      carcinoma to determine the imaging potential of 201Tl, MIBI and 131I in the
      detection of residual or recurrent disease. Eighteen of the 36 patients had
      undergone 131I ablation. Imaging was performed 20 min following the intravenous
      injection of 111 MBq 201Tl or 555 MBq MIBI, or 48 h after the oral ingestion of
      185 MBq 131I. The overall concordance between the 201Tl, MIBI and 131I scans was
      70%. The concordance between thyroglobulin (TG) levels and the 131I scans was
      78%; that between the 201Tl and MIBI scans and TG levels was 83%. Among the group
      of pre-ablative patients, there were six false-negative results with 201Tl and
      three false-negative results with MIBI. Among the post-ablation group, the 201Tl
      and MIBI scans were falsely negative in five patients. The 131I scans revealed
      all known residual or recurrent diseases. In conclusion, 201Tl, MIBI or TG levels
      should not be used in the place of 131I for the detection of residual or
      recurrent thyroid cancer. However, in patients who have not had their TSH
      suppressing doses of T4 or T3 withdrawn, the role of 201Tl and MIBI is debatable.

PMID- 8736513
TI  - Quantification of extracorporeal white cell and platelet deposition in
      cardiopulmonary bypass: comparison of membrane and bubble oxygenators.
AB  - Cardiopulmonary bypass is known to activate both white cells and platelets. The
      aim of this study was to investigate whether the use of bubble and membrane
      oxygenators results in different degrees of deposition in the filter and
      oxygenator of the bypass circuit. Dual-isotope imaging techniques were employed,
      with white cells labelled with 99Tcm and platelets with 111In, and with
      subsequent imaging of the filters and oxygenators on a gamma camera fitted with a
      medium-energy, parallel-hole collimator, relative to a known standard. The
      percentage white cell oxygenator deposition ranged from 0.011 to 4.91% in the
      bubble group (n = 20) and was not different from the membrane group (0.001 to
      4.22%). Similarly, no difference in platelet deposition was found, with 0.605
      45.17% deposited in the bubble oxygenators and 0.001-15.26% deposited in the
      membrane oxygenators. Filter deposition of both types of cell was substantially
      lower in both membrane and bubble groups with no difference between groups. The
      striking feature of the data is the non-normal distribution of the deposition in
      both types of oxygenator. This study demonstrated that both white cell and
      platelet deposition in the cardiopulmonary bypass circuit can be quantified using
      radiolabelled cells. No differences in oxygenator or filter deposition were found
      in patients randomly allocated to membrane or bubble oxygenation.

PMID- 8736514
TI  - Bone mineral density in patients with spinal cord injuries.
AB  - The bone mineral density (BMD) of 157 patients with a spinal cord injury (SCI)
      was measured using dual-photon absorptiometry (Lunar DP-4). The BMD of the second
      to fourth lumbar vertebrae (L2-L4) and the right femoral neck was measured and
      the mean density registered in grams per square centimetre. The likelihood of a
      fracture was based on the percentage of BMD in young normals and the degree of
      risk of fracture. The following criteria were used to separate the patients: (1)
      complete or incomplete immobility due to the SCI; (2) the time between the SCI
      and measurement of BMD was short (<or= 3 years) or long (> 3 years); (3) the
      level at which the SCI occurred was considered to be high (i.e. from the first
      cervical vertebra to the tenth thoracic vertebra) or low (i.e. from the eleventh
      thoracic vertebra to the first lumbar vertebra). The rate of abnormal BMD (i.e. a
      greater risk of fracture) in each of the groups and at each site was measured and
      differences evaluated using the chi-square test. Fifty-four of the 157 (34%)
      scans revealed an abnormal BMD at the level of L2-L4 and 126 (80%) in the right
      femoral neck. The difference between these two incidences was significant (P <
      0.001). However, there were no significant differences in abnormal BMD with
      regard to severity of the SCI, time elapsing since the SCI and level at which the
      SCI occurred. We conclude that hip demineralization is a common complication in
      SCI, but that lumbar BMD is better preserved.

PMID- 8736515
TI  - Bone SPET of symptomatic lumbar spondylolysis.
AB  - The aim of this study was to clarify the clinical role of bone single photon
      emission tomography (SPET) of the lumbar spine in young persons with persistent
      lumbar pain which might be due to spondylolysis. Thirty-one bone SPET studies
      were performed on 25 patients (19 males, 6 females) aged 7-26 years (average 15.6
      years) who had suffered lumbar pain associated with physical activity, and who
      were suspected of having spondylolysis. Planar and SPET images of the lumbar
      spine were obtained 2-3 h following the injection of 99Tc(m)-methylene
      diphosphonate using a single-head rotating gamma camera. The findings on the bone
      scintigram were compared with those on the radiograph. Bone scintigraphy at
      presentation was positive in only 7 of 15 sites of the pars interarticularis
      defects demonstrated on plain radiographs. On the other hand, seven sites of the
      pars interarticularis which were normal on the radiograph were positive on bone
      SPET. As clinical symptoms improved after immobilization using a lumbar corset,
      bone SPET tended to revert towards normal. The planar image was abnormal in only
      8 (42%) of the 19 abnormal sites on the SPET image. A bone SPET study is
      indicated in patients who are negative on radiological tests and who are still
      suspected of having spondylolysis. If SPET is positive in these patients, the
      increased bone uptake is most likely suggestive of a state of 'stress reaction',
      and may be a good indicator for patient management. If negative, further
      radiological examinations will be required for proper assessment of the origin of
      lumbar pain.

PMID- 8736516
TI  - 'Reverse redistribution pattern' during myocardial perfusion imaging with 99Tcm
      MIBI.
AB  - We retrospectively studied 540 consecutive patients with coronary artery disease
      (CAD) undergoing 99Tcm-methoxy-isobutyl-isonitrile (99Tcm-MIBI) myocardial single
      photon emission tomography (SPET) to determine the incidence of the 'reverse
      redistribution pattern' (RRP). RRP is similar to reverse redistribution (RR) in
      201Tl myocardial SPET and is defined as the presence of a perfusion defect on the
      resting cardiac image, rather than on the exercise image. Our results confirmed
      30 (5.6%) patients to have RRP, all of whom underwent diagnostic coronary
      angiography. None of the 30 patients showed RRP in the territory of the left
      circumflex coronary artery. RRP occurred in the territory of the left anterior
      descending coronary artery (LAD) in 16 patients, 12 of whom had a normal LAD.
      Fourteen patients presented with RRP in the territory of the right coronary
      artery, all of whom had normal coronary arteries. RRP in 99Tcm-MIBI myocardial
      SPET is less common than RR in 201Tl myocardial SPET and is frequently associated
      with normal coronary arteries. RRP with 99Tc(m)-MIBI seems to be of little value
      in the diagnosis of CAD.

PMID- 8736517
TI  - Stress/injection protocols for myocardial scintigraphy with 99Tcm-sestamibi
      compared with 201Tl: implications of early post-stress kinetics.
AB  - Stress/injection protocols developed for myocardial perfusion imaging with 201Tl
      may not be optimal for 99Tcm-sestamibi (MIBI), an agent with lower myocardial
      extraction and higher abdominal uptake; prolongation of exercise after
      radiotracer injection might improve these relative drawbacks of MIBI. We compared
      the kinetics of MIBI and 201Tl by acquiring dynamic planar images for 5-7 min
      after a bolus injection (n = 180 studies) with stress performed by supine bicycle
      exercise alone, intravenous dipyridamole or combined stress. Routine or prolonged
      protocols involved continuation of exercise for 1 or 2.5 min respectively after
      tracer appearance in the heart. Subsequently, the perfusion images obtained were
      categorized as normal or showing significant defects. Myocardial uptake of MIBI,
      normalized for injected dose, body weight and camera sensitivity, was only 40% of
      that for 201Tl; there were no differences based on test mode or scan result for
      either perfusion tracer. During the second minute after injection, the
      cavity/myocardial ratios, an index of blood pool activity, were elevated with
      MIBI by 25% when compared with 201Tl (P < 0.001). During the third minute, cavity
      activity was again higher with MIBI, but only in those subjects with abnormal
      scans. The prolonged exercise phase did not prevent progressive accumulation in
      the abdomen, but did allow cavity levels to decline before termination of
      exercise. The prolonged protocol may ensure that myocardial uptake of MIBI is
      completed during peak blood flow, and therefore is recommended for stress with
      exercise or with dipyridamole and exercise in combination.

PMID- 8736518
TI  - A variable threshold edge-detector for improved quantitation of gated tomographic
      imaging of the left ventricular blood pool.
AB  - The accurate measurement of left ventricular volume from tomographic MUGA studies
      is difficult due to the limited resolving power of the gamma camera, which causes
      errors in the detection of the correct ventricular boundaries. Therefore, the use
      of fixed threshold or second-derivative edge-detectors results in overestimates
      at small volumes. A variable threshold edge-detection technique was developed to
      overcome this. Computer-simulated short-axis slices through the heart over a
      range of left ventricular dimensions were convolved by the Point Spread Response
      Function of the system to model the acquired image. The maximum pixel value and
      the threshold value required to detect the true ventricular edge from each
      simulation were then combined into a look-up table for the calculation of the
      required threshold value. As the dimension of the ventricle decreased, the
      threshold value chosen to detect the ventricular edge increased. Left ventricular
      volumes and ejection fraction measurements were calculated for seven patients
      using cine-MRI as the gold-standard technique for validation of the proposed
      method. The single photon emission tomographic studies were analysed using both
      the standard second-derivative edge-detection software and the proposed variable
      threshold technique. The variable threshold technique was shown to increase
      significantly the accuracy of ventricular volume measurements and ejection
      fraction calculations. The average error in the measurement of volumes was
      reduced from 41.4 +/- 45.1% to 18.5 +/- 14.6% and the accuracy of ejection
      fraction measurement was increased from 29.7 +/- 4.6% to 11.3 +/- 6.9%.

PMID- 8736519
TI  - The role of 99Tcm-HMPAO brain SPET in paediatric traumatic brain injury.
AB  - Twenty-eight paediatric patients suffering from chronic sequelae of traumatic
      brain injury (TBI) were examined by EEG, radionuclide imaging with 99Tcm
      hexamethylpropyleneamine oxime (99Tcm-HMPAO), computed tomography (CT) and, when
      available, magnetic resonance imaging (MRI), the results of which were evaluated
      retrospectively. Our findings indicate that neuro-SPET (single photon emission
      tomography) with 99Tcm-HMPAO is more sensitive than morphological or
      electrophysiological tests in detecting functional lesions. In our group, 15 of
      32 CT scans were normal, compared with 3 of 35 SPET studies. SPET identified
      approximately 2.5 times more lesions than CT (86 vs 34). SPET was found to be
      particularly sensitive in detecting organic abnormalities in the basal ganglia
      and cerebellar regions, with a 3.6:1 detection rate in the basal ganglia and a
      5:1 detection rate in the cerebellum compared with CT. In conclusion, neuro-SPET
      appears to be very useful when evaluating paediatric post-TBI patients in whom
      other modalities are not successful.

PMID- 8736520
TI  - Radiopharmaceutical dosage of 99Tcm-HMPAO for cerebral blood flow SPET studies in
      children.
AB  - Four methods of calculating the activity of 99Tcm-hexamethylpropyleneamine oxime
      to be administered in cerebral blood flow investigations of children were
      evaluated in patient studies. Three of the methods were based on the size of the
      child. We also constructed a theoretical dosage model based on physiological data
      and attenuation effects. The aim of the study was to find a dosage calculation
      method that gave the same image quality for children of all ages as well as for
      adults. The results showed that the dosage method based on body weight is the
      only one of the four methods that does not exhibit an age-dependent variation in
      image quality and therefore this method is recommended.

PMID- 8736521
TI  - Accumulation of 99Tcm-polyclonal immunoglobulin in different stages of infection:
      an experimental study.
AB  - In this experimental study, the utility of 99Tc(m)-polyclonal human
      immunoglobulin (99Tcm-HIG) for localizing acute and chronic phases of
      inflammatory lesions was investigated. Three groups of rats were inoculated with
      Staphylococcus aureus in the right thigh. Then, 24 h (group I, n = 12), 48 h
      (group II, n = 12) and 72 h (group III, n = 12) post-inoculation, the rats
      received 40 MBq 99Tcm-HIG into the jugular vein. In addition, two control rats
      were studied at 24 h after inoculation of sterile saline. Both visual and
      quantitative evaluations were undertaken. The acute and chronic stages of
      inflammation were determined by pathological examination. The mean ( +/- S.D.)
      lesion/contralateral uptake ratios at 4 and 24 h after 99Tcm-HIG injection were:
      group I, 1.22 +/- 0.1 and 2.12 +/- 0.16; group II, 1.15 +/- 0.08 and 2.25 +/-
      0.16; group III, 1.06 +/- 0.09 and 2.08 +/- 0.14. In conclusion, the acute and
      chronic phases of infection showed non-significant differences in 99Tcm-HIG
      uptake ratios.

PMID- 8736522
TI  - Origin of the Patlak-Rutland plot.

PMID- 8736523
TI  - Radiation protection issues associated with nuclear medicine out-patients.

PMID- 8736524
TI  - Radiation protection issues.

PMID- 8736525
TI  - A flexible partnership: the CytR anti-activator and the cAMP-CRP activator
      protein, comrades in transcription control.
AB  - A vital point in gene regulation is control at the level of transcription
      initiation. Recent research has established that this regulation can involve
      sophisticated networks of interacting proteins that modulate the activity of the
      transcription machinery by DNA looping, direct protein-protein interactions or
      changing DNA topology in the promoter region. This Micro-Review focuses on our
      investigations of a relatively simple prokaryotic gene regulatory system, the
      Escherichia coli CytR regulon, which exhibits a number of these features. This
      work has opened the door to the molecular understanding of how a prokaryotic
      repressor can be correctly positioned at specific DNA sequences with the help of
      a global activator, and how the repressor subsequently inhibits factor-dependent
      transcription initiation.

PMID- 8736526
TI  - Very short patch repair: reducing the cost of cytosine methylation.
AB  - In Escherichia coli and related bacteria, the product of gene dcm methylates the
      second cytosine of 5'-CCWGG sequences (where W is A or T). Deamination of 5
      methylcytosine (5meC) results in C to T mutations. The mutagenic potential of
      5meC is reduced by a system called very short patch (VSP) repair, which replaces
      T with C. T:G and U:G mispairs in the methylatable sequence and in related
      sequences are recognized by the product of vsr, a gene adjacent to dcm. Vsr
      creates a nick just 5' of the mispaired pyrimidine to initiate the repair.
      Additional products known to be required for VSP repair are DNA polymerase I and
      DNA ligase. MutS and MutL have a stimulatory role but are not required. The
      ability of Vsr to recognize T:G mispairs in sequences related to CCWGG is
      probably responsible for over- and under-representation of certain
      tetranucleotides in the E. coli genome. Although VSP repair reduces spontaneous
      mutations at 5meCs in replicating bacteria, mutation hot-spots persist at these
      sites. Under conditions that more accurately mimic the natural environment of E.
      coli, VSP repair appears to be effective in preventing mutation at 5meC.

PMID- 8736527
TI  - A newly identified gene cluster in Aspergillus nidulans comprises five novel
      genes localized in the alc region that are controlled both by the specific
      transactivator AlcR and the general carbon-catabolite repressor CreA.
AB  - Ethanol-utilization in Aspergillus nidulans is mediated by alcohol dehydrogenase
      I and aldehyde dehydrogenase encoded by alcA and aldA, respectively. Both genes
      are under the transcriptional control of the specific activator AlcR and the
      general carbon catabolite repressor CreA. The alcR and alcA genes are closely
      linked in chromosome VII; aldA is located in chromosome VIII. We have identified
      five other transcripts that are expressed from the same genomic region as alcA
      and alcR. They are inducible by the gratuitous inducer ethyl methyl ketone (EMK),
      and are carbon catabolite repressed. The corresponding genes, designated alcM,
      alcS, alcO, alcP, and alcU, are differentially regulated by the specific
      transcriptional activator AlcR, and they are not all under the direct control by
      the CreA repressor. Some of the inducible transcripts are very abundant in the
      cell, whereas others are poorly expressed. Two sets of genes, alcM/alcS and
      alcR/alcO, are divergently transcribed and probably share a common cis-acting
      region, whereas alcP and alcU are individually transcribed from the same strand
      as alcA and alcR, and have their own promoters. The significance of the alc gene
      clustering is discussed. At least four of the five novel alc genes in the cluster
      are not essential for ethanol metabolism.

PMID- 8736528
TI  - Phosphorylation-dependent binding of BvgA to the upstream region of the cyaA gene
      of Bordetella pertussis.
AB  - In Bordetella pertussis, transcription of virulence-associated genes is regulated
      by the BvgS and BvgA proteins, members of the bacterial two-component signal
      transduction family. BvgS is the transmembrane sensor and BvgA, in its
      phosphorylated form, is believed to be the key transcriptional activator in B.
      pertussis. However, the BvgA recognition sites in most virulence promoters have
      not yet been identified. To investigate the interaction of BvgA with the upstream
      region of cyaA, the gene encoding adenylate cyclase haemolysin, we have produced
      large amounts of BvgA in Escherichia coli. The protein was purified from
      inclusion bodies and then phosphorylated by acetyl phosphate. Using
      electrophoretic mobility-shift and footprinting assays, we provide evidence that
      BvgA cannot bind to the cyaA promoter unless it is phosphorylated. The
      phosphorylated form of BvgA (BvgA-P) is able to bind specifically to the upstream
      region of cyaA. Analysis of this region revealed that an unexpectedly large
      sequence, from -137 to -51, appears to be the target for BvgA-P binding, and
      probably contains multiple binding sites.

PMID- 8736529
TI  - Essential roles of core starvation-stress response loci in carbon-starvation
      inducible cross-resistance and hydrogen peroxide-inducible adaptive resistance to
      oxidative challenge in Salmonella typhimurium.
AB  - The starvation-stress response (SSR) of Salmonella typhimurium encompasses the
      physiological changes that occur upon starvation for an essential nutrient, e.g.
      C-source. A subset of SSR genes, known as core SSR genes, are required for the
      long-term starvation survival of the bacteria. Four core SSR loci have been
      identified in S. typhimurium: rpoS, stiA, stiB, and stiC. Here we report that in
      S. typhimurium C-starvation induced a greater and more sustainable cross
      resistance to oxidative challenge (15 mM hydrogen peroxide (H2O2) for 40 min)
      than either N- or P-starvation. Of the four core SSR loci, only rpoS and stiC
      mutants exhibited a defective C-starvation-inducible cross-resistance to H2O2
      challenge. Interestingly, (unadapted) log-phase S. typhimurium rpoS and stiA
      mutants were very sensitive to oxidative challenge. Based on this, we determined
      if these core SSR loci were important for H2O2 resistance developed during a 60
      min adaptive exposure to 60 microM H2O2 (adapted cells). Both unadapted and
      adapted rpoS and stiA mutants were hypersensitive to a H2O2 challenge. In
      addition, a stiB mutant exhibited normal adaptive resistance for the first 20
      mins of H2O2 challenge but then rapidly lost viability, declining to a level of
      about 1.5% of the wild-type strain. The results of these experiments indicate
      that: (i) the rpoS and stiC loci are essential for the development of C
      starvation-inducible cross-resistance to oxidative challenge, and (ii) the rpoS,
      stiA, and, in a delayed effect, stiB loci are needed for H2O2-inducible adaptive
      resistance to oxidative challenge. Moreover, we found that both stiA and stiB are
      induced by a 60 microM H2O2 exposure, but only stiA was regulated (repressed) by
      (reduced form) OxyR.

PMID- 8736530
TI  - Limited variation and maintenance of tight genetic linkage characterize
      heteroallelic pilE recombination following DNA transformation of Neisseria
      gonorrhoeae.
AB  - Genetic recombination impacts on neisserial biology in two ways: (i) specific
      loci undergo rearrangement at high frequency leading to the formation of many
      different alleles; and (ii) Neisseria, being naturally competent for DNA
      transformation, provide a means to disseminate the novel alleles throughout a
      population. In this study pilE was used as a model system to examine
      heteroallelic recombination following DNA transformation. When gonococci were
      transformed with chromosomal donor DNA containing different pilE alleles, the
      majority of pilE recombinants arose through allelic replacement. Co-conversion
      analysis across pilE showed that in approximately 85-90% of recombination events
      encompassing pilE and an adjacent opa locus, linkage was maintained (i.e.
      approximately 10-15% of recombination events terminated within the approximately
      1000 base pair pilE/opaE interval). In addition to those recombinants that arose
      through allelic replacement, a large pilus-minus subpopulation was also observed
      (approximately 10% of all recombinants), indicating that many recombination
      events did not yield recombinant pilEs that could be assembled into functional
      pili. PilE mosaics increased following transformation with plasmid donor DNAs
      carrying pilE with limited flanking-sequence homology, suggesting a potential
      role for flanking-sequence homologies in mosaic formation. Overall, the data
      support the view that horizontal transmission of chromosomal DNA between
      gonococci will favour the spread of intact alleles, as opposed to expanding the
      allelic repertoire through the formation of gene mosaics.

PMID- 8736531
TI  - The effects on Escherichia coli of expression of the cloned bacteriophage T4
      nucleoid disruption (ndd) gene.
AB  - Immediately after T4 bacteriophage infection, the Escherichia coli nucleoid
      undergoes rapid delocalization. The ndd gene of T4 is responsible for this
      nuclear disruption phenomenon. We have cloned two alleles of this gene and
      studied the effects of their expression on E. coli cells. We have shown that the
      Ndd protein (i) is able to reproduce the disruption of the nucleoid
      characteristic of T4 infection, (ii) is highly toxic and results in a logarithmic
      decrease in cell viability, and (iii) inhibits genomic DNA replication by
      blocking progression of replication forks. Induction of Ndd does not result in
      degradation of genomic DNA and does not significantly alter the general processes
      of transcription and translation during the entire period of exponential cell
      death. These results support the notion that the target of Ndd is some aspect of
      the nucleoid architecture.

PMID- 8736532
TI  - Characterization of a Penicillium chrysogenum gene encoding a PacC transcription
      factor and its binding sites in the divergent pcbAB-pcbC promoter of the
      penicillin biosynthetic cluster.
AB  - Previous work established that pH regulation of gene expression in Aspergillus
      nidulans, a major determinant of penicillin biosynthesis, is mediated by the zinc
      finger transcription factor PacC, an activator of transcription of the
      isopenicillin N synthase gene. We characterize here the pacC gene from the
      efficient penicillin producer Penicillium chrysogenum, which functionally
      complements an A. nidulans pacC null mutation. It encodes a 641-residue
      polypeptide showing 64% identify to A. nidulans PacC and containing three
      putative zinc fingers specifically recognizing a 5'-GCCARG-3' hexanucleotide.
      Penicillium pacC transcript levels are higher under alkaline than under acidic
      growth conditions and elevate at late stages of growth. The gene contains three
      PacC-binding sites in its 5'-upstream region. Transcript levels of pcbC (encoding
      P. chrysogenum isopenicillin N synthase) are low on a repressing carbon source
      and elevated on a derepressing carbon source. With either carbon source, alkaline
      pH elevates pcbC transcript levels, correlating with the presence of seven PacC
      binding sites in the 1.1 kb pcbAB-pcbC intergenic region and strongly suggesting
      that pcbC is under direct pacC control. However, in contrast to the situation in
      A. nidulans, alkaline pH does not override the negative effects of a repressing
      carbon source, revealing differences in the regulation of the penicillin pathway
      between Penicillium and Aspergillus.

PMID- 8736533
TI  - Induction of ammonia monooxygenase and hydroxylamine oxidoreductase mRNAs by
      ammonium in Nitrosomonas europaea.
AB  - In Nitrosomonas europaea, ammonia monooxygenase (AMO) and hydroxylamine
      oxidoreductase (HAO) catalyse the oxidation of ammonia (NH3) to nitrite (NO2-). A
      transcript of 3500 bases hybridizes to probes for amoA and amoB (genes that code
      for AMO proteins). A transcript of 2100 bases hybridizes to probes for hao (the
      gene that codes for HAO). Induction of the mRNAs detected by amo and hao probes
      required the presence of ammonium (NH4+). To correlate new levels of mRNA with de
      novo activity, existent mRNA pools and AMO activity were depleted prior to
      induction by NH4+. The mRNAs of AMO and HAO were depleted by depriving the cells
      of energy for at least 8 h; AMO activity was inactivated with acetylene (C2H2)
      after mRNA depletion. In cells treated this way, levels of new AMO mRNA and de
      novo AMO enzyme activity were correlated with increased NH4+ concentrations up to
      1 mM after 3 h of incubation. HAO mRNA also increased in the NH4(+)-treated
      cells. Other proteins and RNAs induced by NH4+ were detected in 14CO2-labelling
      experiments. The AMO and HAO mRNAs were preferentially synthesized during energy
      limiting conditions.

PMID- 8736534
TI  - Regulation of the expression of the traM gene of the F sex factor of Escherichia
      coli.
AB  - Conjugative F-plasmid transfer is mediated by the transfer (tra) region which
      encodes nearly 40 genes, 25 of which are essential for this process in
      Escherichia coli. TraM is required for conjugation and is encoded on a separate
      operon between the origin of transfer and the traJ gene. The traJ gene product is
      the positive regulator of transcription of the 30 kb tra operon, the first gene
      of which is traY. Using primer-extension assays and immunoblots on the F plasmid
      itself and its derivatives, we demonstrate that F TraM regulates its own
      expression from two promoters and that it requires TraY as well as expression of
      the tra operon for maximal traM transcription. traY is the first gene in the tra
      operon under the control of the TraJ regulator, which is in turn negatively
      regulated by the antisense RNA, FinP, and the FinO protein. Thus, a control
      circuit has been established whereby traM is negatively regulated by the FinOP
      fertility inhibition system through its repression of TraJ expression, which
      adversely affects transcription of the traY gene.

PMID- 8736535
TI  - Identification and sequence of a nifJ-like gene in Rhodospirillum rubrum: partial
      characterization of a mutant unaffected in nitrogen fixation.
AB  - A nifJ-like gene was identified in the photosynthetic purple non-sulphur
      bacterium Rhodospirillum rubrum. A DNA segment hybridizing to Klebsiella
      pneumoniae nifJ was isolated, the gene was inactivated, and a mutant strain, SNJ
      1, was constructed by allele replacement. The mutation was confirmed by DNA
      sequencing. Northern blotting and by the lack of pyruvate oxidoreductase
      activity. This is the first report of a nifJ-like gene in photosynthetic
      bacteria. Unexpectedly, SNJ-1 was capable of nitrogen fixation, and growth was
      similar to the wild-type strain under all conditions investigated. Therefore,
      this is also the first demonstration that a nifJ homologue, when present, is not
      essential for nitrogen fixation in a diazotroph. The nifJ-like gene was sequenced
      and found to have considerable similarity to published nifJ gene sequences from
      other organisms. By primer extension, the initiation site for transcription was
      located, and a typical sigma 54 promoter sequence was identified.

PMID- 8736536
TI  - TOL plasmid transcription factor XylS binds specifically to the Pm operator
      sequence.
AB  - XylS, an AraC family transcription factor, positively regulates transcription of
      Pseudomonas putida TOL plasmid meta operon from the Pm promoter. A tandem of 15
      bp homologous direct repeats, separated by 6 bp and overlapping with the -35
      hexamer of the promoter, is required for the activation of Pm by XylS in vivo. In
      this study we have characterized specific binding of XylS to the Pm operator Om.
      XylS was overexpressed with an epitope tag in its N-terminus. Tagged XylS (N
      XylS) was immunopurified and was shown to specifically bind to Om. We have used
      matrix-bound N-XylS in DNA footprinting and methylation interference experiments.
      Binding of N-XylS protects 44 bp in the Om region on both strands from DNase I
      digestion and generates hypersensitive sites (within the protected area) which
      lie on the same face of the DNA helix. Results of hydroxyl radical footprinting
      and methylation interference assays indicate that XylS binds along one side of
      the DNA and covers four helical turns. The protein has base-specific contacts in
      four adjacent major groove regions on the same helical face. Our data are in
      accord with the prediction of the presence of two separate DNA-binding units in
      an XylS molecule which are involved in base-specific contacts in two adjacent
      major-groove regions of a half-site. The direct repeat arrangement of the binding
      site and the mode of DNA binding of XylS are similar to the arrangement of
      recognition sites and the DNA contact pattern of AraC protein from Escherichia
      coli.

PMID- 8736537
TI  - The centromere-like parC locus of plasmid R1.
AB  - The parA partitioning system of plasmid R1 consists of three components: the cis
      acting centromere-like parC locus, and two proteins, ParM and ParR. The parC
      locus contains two sets of five direct repeats (iterons) to which the ParR
      protein binds. The parA promoter is located in the core region between the two
      sets of iterons. Mini-R1 replicons carrying parC are stabilized by the
      simultaneous presence of ParM and ParR. The parC locus present on a co-resident
      plasmid leads to instability of the mini-R1 replicon (incompatibility). Here we
      present a genetic analysis of the stability and incompatibility phenotypes
      associated with parC. We show that all 10 iterons are required for maximum
      stabilization and incompatibility. Replacement of the core promoter region
      between the repeats by a foreign promoter region did not reduce stabilization.
      Thus, the only structural components in parC seem to be the two sets of iterons.
      The parA promoter, P parA, is repressed by ParR. We show that all 10 iterons are
      required for full repression of the promoter. The activity of the promoter was
      influenced by sequences located outside the core region. An A-rich region located
      upstream of the -35 element of PparA was found to increase promoter activity. The
      region encoding the parA mRNA leader region also strongly influenced the
      expression level of PparA- lacZ fusions. We show that this high expression (hex)
      element is a transcriptional antiterminator that prevents Rho-dependent
      termination.

PMID- 8736538
TI  - The Yersinia YpkA Ser/Thr kinase is translocated and subsequently targeted to the
      inner surface of the HeLa cell plasma membrane.
AB  - Multiple yop mutant strains of Yersinia pseudotuberculosis not expressing several
      virulence effector Yop proteins (YopH, M, E, K and YpkA) were engineered. When
      high-copy-number plasmids carrying the ypkA or the yopE gene with their
      endogenous promoters were introduced into the engineered strains, the
      corresponding Yop protein was secreted at high levels in vitro. These multiple
      yop mutant strains, when harbouring the yopE gene in trans, behaved as the wild
      type strain with respect to YopB-dependent translocation of YopE through the HeLa
      cell plasma membrane. Using these multiple yop mutant strains, it was
      demonstrated that the YpkA Ser/Thr protein kinase mediates morphological
      alterations of infected cultured HeLa cells different from those mediated by YopE
      and YopH. Furthermore, YpkA is shown to be translocated by a YopB-dependent
      translocation mechanism from surface-located bacteria and subsequently targeted
      to the inner surface of the target-cell plasma membrane. The pattern of YpkA
      localization after infection suggests that this Yop effector is involved in
      interference with signal transduction.

PMID- 8736539
TI  - Internal pH crisis, lysine decarboxylase and the acid tolerance response of
      Salmonella typhimurium.
AB  - Salmonella typhimurium possesses an adaptive response to acid that increases
      survival during exposure to extremely low pH values. The acid tolerance response
      (ATR) includes both log-phase and stationary-phase systems. The log-phase ATR
      appears to require two components for maximum acid tolerance, namely an inducible
      pH homeostasis system, and a series of acid-shock proteins. We have discovered
      one of what appears to be a series of inducible exigency pH homeostasis systems
      that contribute to acid tolerance in extreme acid environments. The low pH
      inducible lysine decarboxylase was shown to contribute significantly to pH
      homeostasis in environments as low as pH 3.0. Under the conditions tested, both
      lysine decarboxylase and sigma s-dependent acid-shock proteins were required for
      acid tolerance but only lysine decarboxylase contributed to pH homeostasis. The
      cadBA operon encoding lysine decarboxylase and a lysine/cadaverine antiporter
      were cloned from S. typhimurium and were found to be 79% homologous to the cadBA
      operon from Escherichia coli. The results suggest that S. typhimurium has a
      variety of means of fulfilling the pH homeostasis requirement of the ATR in the
      form of inducible amino acid decarboxylases.

PMID- 8736540
TI  - Accessory proteins impose site selectivity during ColE1 dimer resolution.
AB  - The cer-Xer dimer resolution system of plasmid ColE1 is highly selective, acting
      only at sites on the same molecule and in direct repeat. Recombination requires
      the XerCD recombinase and accessory proteins ArgR and PepA. The Escherichia coli
      chromosome dimer resolution site dif and the type II hybrid site use the same
      recombinase but are independent of ArgR and PepA and show no site selectivity.
      This has led to the proposal that ArgR and PepA are responsible for the
      imposition of constraint. We describe here the characterization of a novel class
      of "conditionally constrained' multimer resolution sites whose properties support
      this hypothesis. In the presence of ArgR and PepA, plasmids containing
      conditionally constrained sites are monomeric, but in their absence, extensive
      multimerisation is seen. A mutant ArgR derivative (ArgR110), which is defective
      in cer-mediated dimer resolution, remains able to prevent plasmid multimerisation
      by a conditionally constrained site. This implies that the accessory factors
      block recombination in trans rather than ensuring rapid multimer resolution. When
      the distance between the ArgR and XerCD binding sites in a conditionally
      constrained site was altered by a non-integral number of helical turns, the site
      became unconstrained. Constraint was restored by the insertion of a full helical
      turn.

PMID- 8736541
TI  - Analysis of nitrate regulatory protein NarL-binding sites in the fdnG and narG
      operon control regions of Escherichia coli K-12.
AB  - During anaerobic growth, expression of the fdnGHI and narGHJI operons of
      Escherichia coli is induced by the NarL protein in response to nitrate. The fdnG
      operon control region contains four NarL-binding sites (termed NarL heptamers)
      between positions -70 and -130. The two central NarL heptamers of fdnG are
      arranged as an inverted repeat and are essential for regulation by NarL. We used
      mutational analysis of these central heptamers to investigate the precise
      sequence requirements for NarL-dependent induction. Mutations were examined for
      their effects on NarL-dependent expression in vivo. Substitutions at position 1
      of either heptamer had the strongest effect whereas substitutions at position 7
      had the weakest effect. For some positions, alterations in both heptamers had a
      stronger effect than either of the single changes. The 2 bp spacing between these
      NarL heptamers was also important for normal nitrate induction. The narG operon
      control region has at least eight NarL heptamers arranged in two groups. Previous
      work has shown that nucleotide substitutions in two of these heptamers, centred
      at positions -195 and -89, severely reduce nitrate induction of narG operon
      expression in vivo and significantly interfere with NarL-DNA interactions in
      vitro. Substitutions in heptamers -185 and -101 affected narG operon induction
      only when the concentration of phospho-NarL was low (during growth in the
      presence of nitrite). Changes in each of the other four NarL heptamers studied
      had little or no effect on nitrate or nitrite induction of narG operon expression
      or on NarL-DNA interactions in vitro.

PMID- 8736542
TI  - STAB-SD: a Shine-Dalgarno sequence in the 5' untranslated region is a determinant
      of mRNA stability.
AB  - Transcription of the Bacillus thuringiensis cryIIIA toxin gene is initiated at
      nucleotide position -558 (relative to the cryIIIA start codon). However, the
      major cryIIIA transcript is an mRNA with its 5' end at nucleotide position -129.
      Fusions to the lacZ reporter gene revealed that the cryIIIA 5' untranslated
      region downstream of nucleotide position -129 acts as a 5' mRNA stabilizer.
      Deletion and mutation analysis suggest that the determinant of stability is a
      Shine-Dalgarno (SD) sequence close to the 5' end of the stable transcript. This
      SD sequence, designated STAB-SD, does not direct translation initiation. However,
      mutations predicted to weaken the putative interaction between the SD sequence
      and the 3' end of 16S rRNA lead to reduced mRNA stability. The binding of a 30S
      subunit to STAB-SD may be required for stabilization of cryIIIA mRNA as a
      transcript with a 5' end at nucleotide position -129. Similar STAB-SD sequences
      are found in the 5' untranslated regions of other cryIII genes, and in the 5'
      untranslated regions of genes from Gram-positive bacteria other than B.
      thuringiensis and may therefore be a widespread determinant of mRNA stability.

PMID- 8736543
TI  - Identification and characterization of FrzZ, a novel response regulator necessary
      for swarming and fruiting-body formation in Myxococcus xanthus.
AB  - The frz genes of Myxococcus xanthus constitute a signal-transduction pathway that
      processes chemotactic information in a manner analogous to that found in enteric
      bacteria. Ultimately, these genes regulate the frequency of individual cell
      reversal. We report here the identification of a novel component of this signal
      transduction pathway, designated frzZ, which was discovered as an open reading
      frame located 5' to the frz operon but transcribed in the opposite orientation.
      The translational start site of frzZ is 170 base pairs from that of frzA.frzZ
      utilizes a promoter similar to the sigma 70 promoters of Escherichia coli, and
      encodes a 290-amino-acid soluble protein, FrzZ (M(r) 30,500). FrzZ contains two
      domains, both of which show strong homology to CheY and other members of the
      response-regulator family. Linking these domains is a 39-amino-acid region that
      is very rich in alanine and proline (38% Ala and 33% Pro). A frzZ null mutant
      showed abnormally low reversal rates when compared to the wild-type control and
      was unable to form fruiting bodies on starvation medium, but it did form 'frizzy'
      aggregates. In addition, the frzZ mutant was defective in swarming, particularly
      on soft agar (0.3% w/v). However, unlike most frz mutants, the frzZ mutant was
      able to respond to attractants and repellents in the spatial chemotaxis assay.
      The discovery of FrzZ demonstrates that the M. xanthus frz signal-transduction
      pathway utilizes multiple response-regulator (CheY-like) proteins.

PMID- 8736544
TI  - Isolation and characterization of insertional mutations in flagellin genes in the
      archaeon Methanococcus voltae.
AB  - Methanococcus voltae is a flagellated member of the Domain Archaea that has four
      flagellin genes arranged in two transcriptional units. One transcriptional unit
      encodes only flaA while the second is a multi-cistronic unit encoding three
      flagellin genes (flaB1, flaB2, and flaB3) as well as at least seven other open
      reading frames downstream. The polymerase chain reaction was used to amplify an
      internal fragment of the flaA gene which was subsequently cloned into an
      insertion vector developed for M. voltae. Transformation of protoplasts with this
      vector led to the isolation of mutant strains that had insertions in flaA or
      flaB2. Mutant strains carrying insertions in flaA had flagelia that were similar
      to wild-type cells in both number and appearance when viewed using the electron
      microscope. In addition, some of these mutant strains had profiles identical to
      the wild type in immunoblots developed with antisera raised against the 31 kDa
      flagellin of M. voltae. All flaA mutant strains and the wild-type cells showed
      immuno-cross-reactive bands at 33 and 31 kDa (corresponding to purified
      flagellins) as well as at 18 kDa. Some flaA mutant strains also showed an immuno
      cross-reactive band at 27 kDa which probably represents a truncated flagellin
      produced by the insertion vector. However, both types of flaA mutant strains were
      less motile than the wild type in semi-swarm plate experiments. The mutant strain
      with an insertion in flaB2 was non-flagellated when examined by electron
      microscopy and it was non-motile in semi-swarm plate experiments. It represents
      the first structural mutant strain isolated in a methanogen. This mutant strain
      lacked the 33, 31, and 18 kDa immuno-cross-reactive bands observed in the wild
      type and flaA mutant strains, and instead had a novel band at 20 kDa. This band
      may represent an unmodified flagellin which still has an attached leader peptide.
      If so, then one of the downstream genes in the multi-cistronic transcriptional
      unit may encode a leader peptidase for the flagellin system.

PMID- 8736545
TI  - The Aspergillus fumigatus chsC and chsG genes encode class III chitin synthases
      with different functions.
AB  - Two genes, designated chsC and chsG were isolated from DNA libraries of the
      opportunistic fungal pathogen, Aspergillus fumigatus. The genes were
      characterized with respect to their nucleotide sequences and mutant phenotypes.
      The complete deduced amino acid sequences of chsC and chsG show that the products
      of both genes are Class III zymogen-type enzymes. A mutant strain constructed by
      disruption of chsC is phenotypically indistinguishable from the wild-type strain,
      but chsG- and chsC- chsG- strains have reduced colony radial growth rate and
      chitin synthase activity, conidiate poorly and produce highly branched hyphae.
      Despite these defects, the double-mutant strain retained the ability to cause
      pulmonary disease in neutropenic mice. However, in comparison to the wild-type
      strain, there was a decrease in mortality and delay in the onset of illness in
      mice inoculated with the double-mutant strain, which was associated with smaller
      and more highly branched fungal colonies in lung tissue.

PMID- 8736546
TI  - Unified nomenclature for broadly conserved hrp genes of phytopathogenic bacteria.

PMID- 8736547
TI  - WW domains.
AB  - WW domains are recently described protein-protein interaction modules; they bind
      to proline-rich sequences that usually also contain a tyrosine. These domains
      have been detected in several unrelated proteins, often alongside other domains.
      Recent studies suggest that WW domains in specific proteins may play a role in
      diseases such as hypertension or muscular dystrophy.

PMID- 8736548
TI  - Kinesin and myosin: molecular motors with similar engines.
AB  - Structure determination of the catalytic domains of two members of the kinesin
      superfamily reveals that this class of molecular motor exhibits the same
      architecture as myosin and suggests that these microtubule- and actin-based
      motors arose from a common ancestor.

PMID- 8736549
TI  - The reactivity of B12 cofactors: the proteins make a difference.
AB  - Determination of the structure of intact methylmalonyl-CoA mutase from
      Propionibacterium shermanii, and comparisons with the structure of the cobalamin
      binding fragment of methionine synthase from Escherichia coli, afford a first
      glimpse at the similarities and distinctions between the two principal classes of
      B12-dependent enzymes: the mutases and the methyltransferases.

PMID- 8736551
TI  - Aromatic interactions define the binding of the alphavirus spike to its
      nucleocapsid.
AB  - BACKGROUND: Most enveloped viruses bud from infected cells by a process in which
      viral intracellular core components interact with cytoplasmic domains of
      transmembrane spike glycoproteins. We have demonstrated previously that a
      tyrosine motif in the cytoplasmic domain of the Semliki Forest virus (SFV) spike
      glycoprotein E2 is absolutely essential for budding. In contrast, hardly anything
      is known regarding which region of the capsid protein is involved in spike
      binding. Therefore, the mechanism by which spikes are selectively sorted into the
      viral bud or by which energy is provided for envelopment, remains unclear.
      RESULTS: Molecular models of the SFV capsid protein (SFCP) and the cytoplasmic
      domain of the spike protein were fitted as a basis for a reverse genetics
      approach to characterizing the interaction between these two proteins.
      Biochemical analysis of mutants defined a hydrophobic pocket of the capsid
      protein that is involved both in spike binding and nucleocapsid assembly.
      CONCLUSIONS: We suggest that aromatic residues in the capsid protein serve to
      bind the side chain of the essential E2 tyrosine providing both specificity for
      spike incorporation and energy for budding. The same hydrophobic pocket also
      appears to play a role in capsid assembly. Furthermore, the results suggest that
      budding may occur in the absence of preformed nucleocapsids. This is the first
      demonstration of the molecular mechanisms of spike-nucleocapsid interactions
      during virus budding.

PMID- 8736550
TI  - The suitability of multi-metal clusters for phasing in crystallography of large
      macromolecular assemblies.

PMID- 8736552
TI  - Identification of a protein binding site on the surface of the alphavirus
      nucleocapsid and its implication in virus assembly.
AB  - BACKGROUND: Many enveloped viruses exit cells by budding from the plasma
      membrane. The driving force for budding is the interaction of an inner protein
      nucleocapsid core with transmembrane glycoprotein spikes. The molecular details
      of this process are ill defined. Alphaviruses, such as Sindbis virus (SINV) and
      Semliki Forest virus (SFV), represent some of the simplest enveloped viruses and
      have been well characterized by structural, genetic and biochemical techniques.
      Although a high-resolution structure of an alphavirus has not yet been attained,
      cryo-electron microscopy (cryo-EM) has been used to show the multilayer
      organization at 25 A resolution. In addition, atomic resolution studies are
      available of the C-terminal domain of the nucleocapsid protein and this has been
      modeled into the cryo-EM density. RESULTS: A recombinant form of Sindbis virus
      core protein (SCP) was crystallized and found to diffract much better than
      protein extracted from the virus (2.0 A versus 3.0 A resolution). The new
      structure showed that amino acids 108 to 111 bind to a specific hydrophobic
      pocket in neighboring molecules. Re-examination of the structures derived from
      virus-extracted protein also showed this 'N-terminal arm' binding to the same
      hydrophobic pocked in adjacent molecules. It is proposed that the binding of
      these capsid residues into the hydrophobic pocket of SCP mimics the binding of E2
      (one of two glycoproteins that penetrate the lipid bilayer of the viral envelope)
      C-terminal residues in the pocket. Mutational studies of capsid residues 108 and
      110 confirm their role in capsid assembly. CONCLUSIONS: Structural and mutational
      analyses of residues within the hydrophobic pocket suggest that budding results
      in a switch between two conformations of the capsid hydrophobic pocket. This is
      the first description of a viral budding mechanism in molecular detail.

PMID- 8736553
TI  - The crystal structure of bacteriophage Q beta at 3.5 A resolution.
AB  - BACKGROUND: The capsid protein subunits of small RNA bacteriophages form a T = 3
      particle upon assembly and RNA encapsidation. Dimers of the capsid protein
      repress translation of the replicase gene product by binding to the ribosome
      binding site and this interaction is believed to initiate RNA encapsidation. We
      have determined the crystal structure of phage Q beta with the aim of clarifying
      which factors are the most important for particle assembly and RNA interaction in
      the small phages. RESULTS: The crystal structure of bacteriophage Q beta
      determined at 3.5 A resolution shows that the capsid is stabilized by disulfide
      bonds on each side of the flexible loops that are situated around the fivefold
      and quasi-sixfold axes. As in other small RNA phages, the protein capsid is
      constructed from subunits which associate into dimers. A contiguous ten-stranded
      antiparallel beta sheet facing the RNA is formed in the dimer. The disulfide
      bonds lock the constituent dimers of the capsid covalently in the T = 3 lattice.
      CONCLUSIONS: The unusual stability of the Q beta particle is due to the tight
      dimer interactions and the disulfide bonds linking each dimer covalently to the
      rest of the capsid. A comparison with the structure of the related phage MS2
      shows that although the fold of the Q beta coat protein is very similar, the
      details of the protein-protein interactions are completely different. The most
      conserved region of the protein is at the surface, which, in MS2, is involved in
      RNA binding.

PMID- 8736554
TI  - The structure of elongation factor G in complex with GDP: conformational
      flexibility and nucleotide exchange.
AB  - BACKGROUND: Elongation factor G (EF-G) catalyzes the translocation step of
      translation. During translocation EF-G passes through four main conformational
      states: the GDP complex, the nucleotide-free state, the GTP complex, and the
      GTPase conformation. The first two of these conformations have been previously
      investigated by crystallographic methods. RESULTS: The structure of EF-G-GDP has
      been refined at 2.4 A resolution. Comparison with the nucleotide-free structure
      reveals that, upon GDP release, the phosphate-binding loop (P-loop) adopts a
      closed conformation. This affects the position of helix CG, the switch II loop
      and domains II, IV and V. Asp83 has a conformation similar to the conformation of
      the corresponding residue in the EF-Tu/EF-Ts complex. The magnesium ion is absent
      in EF-G-GDP. CONCLUSIONS: The results illustrate that conformational changes in
      the P-loop can be transmitted to other parts of the structure. A comparison of
      the structures of EF-G and EF-Tu suggests that EF-G, like EF-Tu, undergoes a
      transition with domain rearrangements. The conformation of EF-G-GDP around the
      nucleotide-binding site may be related to the mechanism of nucleotide exchange.

PMID- 8736555
TI  - Structure of a water soluble fragment of the 'Rieske' iron-sulfur protein of the
      bovine heart mitochondrial cytochrome bc1 complex determined by MAD phasing at
      1.5 A resolution.
AB  - BACKGROUND: The 'Rieske' iron-sulfur protein is the primary electron acceptor
      during hydroquinone oxidation in cytochrome bc complexes. The spectroscopic and
      electrochemical properties of the 'Rieske' [2Fe-2S] cluster differ significantly
      from those of other iron-sulfur clusters. A 129-residue water soluble fragment
      containing the intact [2Fe-2S] cluster was isolated following proteolytic
      digestion of the bc1 complex and used for structural studies. RESULTS: The
      structure of the Rieske iron-sulfur fragment containing the reduced [2Fe-2S]
      cluster has been determined using the multiwavelength anomalous diffraction (MAD)
      technique and refined at 1.5 A resolution. The fragment has a novel overall fold
      that includes three sheets of beta strands. The iron atoms of the [2Fe-2S]
      cluster are coordinated by two cysteine (Fe-1) and two histidine (Fe-2) residues,
      respectively, with the histidine ligands completely exposed to the solvent. This
      is in contrast to the four cysteine coordination pattern observed in previously
      characterised [2Fe-2S] ferredoxins. The cluster-binding fold is formed by two
      loops connected by a disulfide bridge; these loops superpose with the metal
      binding loops of rubredoxins. The environment of the cluster is stabilised by an
      extensive hydrogen-bond network. CONCLUSIONS: The high-resolution structure
      supports the proposed coordination pattern involving histidine ligands and
      provides a basis for a detailed analysis of the spectroscopic and electrochemical
      properties. As the cluster is located at the tip of the protein, it might come
      into close contact with cytochrome b. The exposed N epsilon atoms of the
      histidine ligands of the cluster are readily accessible to quinones and
      inhibitors within the hydroquinone oxidation (QP) pocket of the bc1 complex and
      may undergo redox-dependent protonation/deprotonation.

PMID- 8736556
TI  - The crystal structure of the light-harvesting complex II (B800-850) from
      Rhodospirillum molischianum.
AB  - BACKGROUND: The light-harvesting complexes II (LH-2s) are integral membrane
      proteins that form ring-like structures, oligomers of alpha beta-heterodimers, in
      the photosynthetic membranes of purple bacteria. They contain a large number of
      chromophores organized optimally for light absorption and rapid light energy
      migration. Recently, the structure of the nonameric LH-2 of Rhodopseudomonas
      acidophila has been determined; we report here the crystal structure of the
      octameric LH-2 from Rhodospirillum molischianum. The unveiling of similarities
      and differences in the architecture of these proteins may provide valuable
      insight into the efficient energy transfer mechanisms of bacterial
      photosynthesis. RESULTS: The crystal structure of LH-2 from Rs. molischianum has
      been determined by molecular replacement at 2.4 A resolution using X-ray
      diffraction. The crystal structure displays two concentric cylinders of sixteen
      membrane-spanning helical subunits, containing two rings of bacteriochlorophyll-a
      (BChl-a) molecules. One ring comprises sixteen B850 BChl-as perpendicular to the
      membrane plane and the other eight B800 BChl-as that are nearly parallel to the
      membrane plane; eight membrane-spanning lycopenes (the major carotenoid in this
      complex) stretch out between the B800 and B850 BChl-as. The B800 BChl-as exhibit
      a different ligation from that of Rps. acidophila (aspartate is the Mg ligand as
      opposed to formyl-methionine in Rps. acidophila). CONCLUSIONS: The light
      harvesting complexes from different bacteria assume various ring sizes. In LH-2
      of Rs. molischianum, the Qy transition dipole moments of neighbouring B850 and
      B800 BChl-as are nearly parallel to each other, that is, they are optimally
      aligned for Foster exciton transfer. Dexter energy transfer between these
      chlorophylls is also possible through interactions mediated by lycopenes and B850
      BChl-a phytyl tails; the B800 BChl-a and one of the two B850 BChl-as associated
      with each heterodimeric unit are in van der Waals distance to a lycopene, such
      that singlet and triplet energy transfer between lycopene and the BChl-as can
      occur by the Dexter mechanism. The ring structure of the B850 BChl-as is optimal
      for light energy transfer in that it samples all spatial absorption and emission
      characteristics and places all oscillator strength into energetically low lying,
      thermally accessible exciton states.

PMID- 8736557
TI  - The solution structure of the first zinc finger domain of SWI5: a novel
      structural extension to a common fold.
AB  - BACKGROUND: The 2Cys-2His (C2-H2) zinc finger is a protein domain commonly used
      for sequence-specific DNA recognition. The zinc fingers of the yeast
      transcription factors SWI5 and ACE2 share strong sequence homology, which extends
      into a region N-terminal to the first finger, suggesting that the DNA-binding
      domains of these two proteins include additional structural elements. RESULTS:
      Structural analysis of the zinc fingers of SWI5 reveals that a 15 residue region
      N-terminal to the finger motifs forms part of the structure of the first finger
      domain, adding a beta strand and a helix not previously observed in other zinc
      finger structures. Sequence analysis suggests that other zinc finger proteins may
      also have this structure. Biochemical studies show that this additional structure
      increases DNA-binding affinity. CONCLUSIONS: The structural analysis presented
      reveals a novel zinc finger structure in which additional structural elements
      have been added to the C2-H2 zinc finger fold. This additional structure may
      enhance stability and has implications for DNA recognition by extending the
      potential DNA-binding surface of a single zinc finger domain.

PMID- 8736558
TI  - The solution structure of human thioredoxin complexed with its target from Ref-1
      reveals peptide chain reversal.
AB  - BACKGROUND: Human thioredoxin (hTRX) is a 12 kDa cellular redox protein that has
      been shown to play an important role in the activation of a number of
      transcriptional and translational regulators via a thiol-redox mechanism. This
      activity may be direct or indirect via another redox protein known as Ref-1. The
      structure of a complex of hTRX with a peptide comprising its target from the
      transcription factor NF kappa B has previously been solved. To further extend our
      knowledge of the recognition by and interaction of hTRX with its various targets,
      we have studied a complex between hTRX and a Ref-1 peptide. This complex
      represents a kinetically stable mixed disulfide intermediate along the reaction
      pathway. RESULTS: Using multidimensional heteronuclear edited and filtered NMR
      spectroscopy, we have solved the solution structure of a complex between hTRX and
      a 13-residue peptide comprising residues 59-71 of Ref-1. The Ref-1 peptide is
      located in a crescent-shaped groove on the surface of hTRX, the groove being
      formed by residues in the active-site loop (residues 32-36), helix 3, beta
      strands 3 and 5, and the loop between beta strands 3 and 4. The complex is
      stabilized by numerous hydrogen-bonding and hydrophobic interactions that involve
      residues 61-69 of the peptide and confer substrate specificity. CONCLUSIONS: The
      orientation of the Ref-1 peptide in the hTRX-Ref-1 complex is opposite to that
      found in the previously solved complex of hTRX with the target peptide from the
      transcription factor NF kappa B. Orientation is determined by three
      discriminating interactions involving the nature of the residues at the P-2' P-4
      and P-5 binding positions. (P0 defines the active cysteine of the peptide, Cys65
      for Ref-1 and Cys62 for NF kappa B. Positive and negative numbers indicate
      residues N-terminal and C-terminal to this residue, respectively, and vice versa
      for NF kappa B as it binds in the opposite orientation.) The environment
      surrounding the reactive Cys32 of hTRX, as well as the packing of the P+3 to P-4
      residues are essentially the same in the two complexes, despite the opposing
      orientation of the peptide chains. This versatility in substrate recognition
      permits hTRX to act as a wide-ranging redox regulator for the cell.

PMID- 8736559
TI  - Two structurally different RNA molecules are bound by the spliceosomal protein
      U1A using the same recognition strategy.
AB  - BACKGROUND: Human U1A protein binds to hairpin II of U1 small nuclear RNA (snRNA)
      and, together with other proteins, forms the U1 snRNP essential in pre-mRNA
      splicing. U1A protein also binds to the 3' untranslated region (3'UTR) of its own
      pre-mRNA, inhibiting polyadenylation of the 3'end and thereby downregulating its
      own expression. The 3'UTR folds into an evolutionarily conserved secondary
      structure with two internal loops; one loop contains the sequence AUUGCAC and the
      other its variant AUUGUAC. The sequence AUUGCAC is also found in hairpin II of U1
      snRNA; hence, U1A protein recognizes the same heptanucleotide sequence in two
      different structural contexts. In order to better understand the control
      mechanism of the polyadenylation process, we have built a model of the U1A
      protein-3'UTR complex based on the crystal structure of the U1A protein-hairpin
      II RNA complex which we determined previously. RESULTS: In the crystal structure
      of the U1A protein-hairpin II RNA complex the AUUGCAC sequence fits tightly into
      a groove on the surface of U1A protein. The conservation of the heptanucleotide
      in the 3'UTR strongly suggests that U1A protein forms identical sequence-specific
      contacts with the heptanucleotide sequence when complexed with the 3'UTR. The
      crystal structure of the hairpin II complex and the twofold symmetry in the 3'UTR
      RNA provide sufficient information to restrict the conformation of the 3'UTR RNA
      and have enabled us to build a model of the 3'UTR complex. CONCLUSIONS: In the
      U1A-3'UTR complex, sequence-specific interactions are made entirely by the
      conserved heptanucleotide and the last base pair (C:G) of the stem. The structure
      is stabilized by protein-protein contacts and by electrostatic interactions
      between basic amino acids of the protein and the phosphate backbone of the RNA
      stem regions. The formation of a protein dimer necessary for the inhibition of
      poly(A) polymerase requires a conformational change of the C termini of the
      proteins upon RNA binding. This mechanism could prevent the inhibition of poly(A)
      polymerase by free U1A protein. The model is consistent with biochemical data,
      and the protein-protein interactions within the 3'UTR complex account for the
      cooperativity of U1A protein binding to the 3'UTR. The model also serves as an
      important structural guide for designing further experiments to understand the
      interaction between the U1A-3'UTR complex and poly(A) polymerase.

PMID- 8736560
TI  - Location and function of the human frontal eye-field: a selective review.
AB  - The location and possible function of the human frontal eye-field (FEF) were
      evaluated by reviewing results of cerebral blood-flow (CBF) and lesion studies. A
      remarkable consistency was found regarding the rostro-caudal (Y: from -6 to 1 mm)
      and dorso-ventral (Z: from 44 to 51 mm) location of the FEF, as defined by the
      CBF method within a standardized stereotaxic system (the zero point for all X, Y
      and Z coordinates coinciding with the anterior commissure, Talairach and Tournoux
      [Co-planar Stereotactic Atlas of the Human Brain, Georg Thieme, Stuttgart, 1988].
      In contrast, there was a marked variability along the mediolateral axis (X: from 
      24 to -40 mm for the left hemisphere and from 21 to 40 mm for the right
      hemisphere). The human FEF is thus located either in the vicinity of the
      precentral sulcus and/or in the depth of the caudalmost part of the superior
      frontal sulcus. In either case, this location challenges the commonly held view
      of the FEF being located in Broadmann's area 8. With regard to FEF function, the
      results of CBF studies failed to support a role for the FEF in the cognitive
      aspects of oculomotor control, such as the execution of anti-saccades. Blood-flow
      activation data are consistent in this respect with the results of lesion
      studies. It is proposed that future research on FEF function in human subjects
      may benefit from focusing on the visuomotor rather than the cognitive aspects of
      oculomotor control.

PMID- 8736561
TI  - Preserved color imagery in an achromatopsic.
AB  - The loss of color vision secondary to central nervous system disease
      (achromatopsia) is thought to preclude visual imagery of colors. We report a
      patient with achromatopsia, secondary to bilateral temporo-occipital infarcts
      inclusive of the lingual and fusiform gyri, with preserved color imagery. Our
      findings, in conjunction with previous cases in the literature, are consistent
      with a single neural network for color processing in which a disconnection of
      internal activation from stored color representations produces impaired color
      imagery with preserved color perception, whereas a disconnection of visual input
      to these representations produces achromatopsia with preserved color imagery.

PMID- 8736562
TI  - The use of hemi-imagery for studying brain asymmetries in image generation.
AB  - To learn if there are brain asymmetries for image generation we asked 50 right
      handed normal subjects to image one-half of an object and to report which half
      (right or left) they saw. We found that these subjects were more likely to image
      the right half of objects than the left. We also found that right hemi-imagers
      demonstrated a greater degree of right-handedness than did left hemi-imagers. Our
      results suggest that in strongly right-handed subjects the left hemisphere is
      more adept at object image generation than is the right hemisphere.

PMID- 8736563
TI  - Saccadic eye movement programming in unilateral neglect.
AB  - The present study examined the eye movements made by patients with unilateral
      neglect under fixation gap and overlap conditions. The prior offset of fixation
      in a + 100 msec gap condition did not produce an increase in the numbers of
      contralesional saccades made by 3 out of 4 patients. This finding is incompatible
      with the view that the deficit in producing contralesional saccades reflects an
      inability to disengage visual attention from fixation. A significant reduction in
      saccade latency was, however, obtained in the gap condition ('gap effect'). The
      latency reduction in the gap condition is consistent with models which attribute
      the gap effect to warning signal effects and the release of an ocular rather than
      an attentional disengagement mechanism. Saccade latency was not increased when
      two targets were presented bilaterally and simultaneously in both hemifields (in
      contrast to the increase in latency shown by normal subjects). The lack of a
      normal 'bilateral target effect' in neglect is attributed to an imbalance in the
      level of activity in the saccadic system. Three patients showed visual
      'extinction' and did not make saccades to the contralesional bilateral targets.
      In contrast R.R. who shows object-based neglect did not show extinction and made
      saccades to the contralesional bilateral targets. This suggests that visual
      extinction may be influenced by the form of neglect shown by the patient. The
      effects on saccade amplitude of presenting two targets in the same hemifield were
      also examined in a global effect task. One patient showed a much greater global
      effect than normal when pairs of targets were presented in his ipsilesional
      hemifield. In contrast R.R. showed a normal magnitude global effect. It appears
      that the form of neglect shown by a patient is a factor that influences their eye
      movement behaviour on simple saccade tasks and these eye movement abnormalities
      cannot be accounted for by a deficit of attentional disengagement.

PMID- 8736564
TI  - Frontal lesions increase post-target interference in rapid stimulus streams.
AB  - We examined the effects of frontal lesions on the attentional processes
      surrounding the discrimination of target stimuli by comparing patients with
      frontal excisions, patients with temporal excisions and controls on target-letter
      identification in rapid visual streams. Subjects were asked to look at streams of
      18-26 letters presented centrally at rates of 6, 8, or 10 letters/sec and to name
      the two white target letters (T1 and T2) embedded among black letters in each
      stream. The two target letters were separated by either 0, 2,4, or 6 black
      letters. Normals and temporals correctly reported T1 at all rates, they showed
      the expected T2 identification errors peaking 300 msec after T1 at high rate and
      little T2 interference at lower rates. However, frontals showed T2 interference
      at the two lower rates and were unable to identify T1 at high rate. The effects
      observed suggest that an inertia of target discrimination processes contributes
      to the frontal attention deficits.

PMID- 8736565
TI  - Neural systems engaged by planning: a PET study of the Tower of London task.
AB  - The functional anatomy of planning was investigated using the Tower of London
      task. Activation was observed in a distributed network of cortical areas
      incorporating prefrontal, cingulate, premotor, parietal and occipital cortices.
      Activation in corresponding areas has been observed in visuospatial working
      memory tasks with the exception of the rostral prefrontal cortex. This area may
      be identified with the executive components of planning comprising response
      selection and evaluation. Enhanced neural activity in both this rostral
      prefrontal area and the visuospatial working memory system was associated with
      increased task difficulty.

PMID- 8736566
TI  - Asymmetrical memory decline in normal aging and dementia.
AB  - We assessed whether age-associated memory impairments and the memory impairment
      of Alzheimer's disease (AD) is comparable in the verbal and nonverbal domains.
      Subjects incidentally learned the identity and location of a group of objects and
      later verbally recalled the objects as well as recalling their previous spatial
      location. Comparison subject (younger subjects for experiment 1, and older
      subjects for experiment 2) were tested after retention intervals that equated
      their performance with that of the index subjects. We found that memory does not
      change uniformly with age. Verbal memory is more affected than nonverbal memory.
      This asymmetrical pattern is a feature of normal aging and does not appear to be
      due to a degenerative process such as Alzheimer's disease.

PMID- 8736567
TI  - Analysis of the episodic memory deficit in early Alzheimer's disease: evidence
      from the doors and people test.
AB  - Anterograde episodic memory was assessed in a cohort of 33 patients with early
      dementia of Alzheimer type (DAT) and 30 matched controls using immediate and
      delayed prose recall, the CERAD word learning test and the recently developed
      doors and people test of visual and verbal recall and recognition. DAT patients
      showed markedly impaired learning on all three measures, with little evidence of
      cumulation of information across trials. Patients showed more forgetting than
      controls on prose recall and the CERAD word list, but more detailed analysis
      suggested that this differential loss was attributable to the contribution of
      primary memory to immediate but not delayed recall. No differences in forgetting
      rate were observed on the doors and people test. Scaled scores were used to
      derive a recall-recognition index, together with a measure of material-specific
      memory based on the ratio of verbal to visual memory deficits. There was no
      evidence for differential sensitivity of recall over recognition, implying that
      the episodic memory deficit is one of learning, rather than of the retrieval of
      learned material. Although individuals varied in the relative degree of
      impairment of verbal and visual memory, there was no general tendency for
      material-specificity. It was concluded that the episodic memory deficit in DAT is
      general in nature and primarily reflects impaired learning rather than
      accelerated forgetting or disrupted retrieval.

PMID- 8736568
TI  - Recall of frequency of occurrence of self-generated and examiner-provided words
      after frontal or temporal lobectomy.
AB  - Patients with unilateral excisions from the frontal or temporal lobe and normal
      control subjects were given two tasks requiring the recall of the frequency of
      occurrence of words that differed in the number of times they occurred in study
      lists. In one task, subjects were required to generate words in response to cues,
      whilst in the other they merely had to read responses that satisfied the cues.
      All subject groups gave higher frequency estimates to words they had generated
      than to words they had read. Across both tasks, the frontal-lobe groups (left
      more so than right) underestimated frequency of occurrence.

PMID- 8736569
TI  - Movement-related potentials associated with motor inhibition under different
      preparatory states during performance of two visual stop signal paradigms in
      humans.
AB  - The motor-inhibition process was examined in humans by monitoring reaction times
      (RTs), electromyograms (EMGs), and movement-related potentials. Eight subjects
      performed two types of visual stop signal paradigm, one with ongoing motor
      activity and the other without background motor activity. NO-GO-specific negative
      potentials were consistently recorded from subjects with constant onset and
      duration relative to the onset of the NO-GO stimulus in both tasks and the
      spatial distribution of amplitudes was also invariant between the tasks.
      Sustained background muscle activity was not influenced by the inhibitory
      command. The constant features of NO-GO-specific potentials during performance of
      both tasks imply that temporally and spatially similar inhibition processes might
      specifically suppress the execution of a new motor process without any
      significant effect on the ongoing motor programme, regardless of differences in
      preparatory states.

PMID- 8736570
TI  - A case of simulated, psychogenic or focal pure retrograde amnesia: did an entire
      life become unconscious?
AB  - A case of pure retrograde amnesia following mild head injury is reported.
      Neuropsychological, psychodynamic and statistical approaches are employed in an
      attempt to disentangle the clinical picture presented by the patient. Focal
      retrograde amnesia, psychogenic retrograde amnesia and simulated amnesia are all
      taken into account. From a public events questionnaire and an inquiry about
      famous people, consistency analyses showed that the patient was able implicitly
      to use information she denied having, but at the same time, made us lower the
      probability of a simulated amnesia. Moreover, psychodynamic analysis showed that
      the patient's personality structure was compatible with hysterical patterns and
      we suggest that the patient's memory defect may be related to her personality. It
      seems less likely, though still possible, that the case may be explained in terms
      of deliberate simulation. In this case we conclude that the classification along
      the conscious/unconscious dimension seems more informative than the contrast
      between psychogenic and organic genesis.

PMID- 8736571
TI  - Non-verbal auditory recognition in normal subjects and brain-damaged patients:
      evidence for parallel processing.
AB  - Three different aptitudes involved in sound object recognition were tested in 60
      normal subjects and 20 brain-damaged patients: (i) capacity to segregate sound
      objects on different cues (intensity steps, coherent temporal modulations or
      signal onset synchrony); (ii) asemantic recognition of sounds of real objects by
      judging whether two different sound samples belonged to the same object; and
      (iii) semantic identification of sounds of real objects as judged by means of a
      multiple choice response test. In 12 patients, different aptitudes involved in
      auditory recognition were disrupted separately and in a way which speaks in
      favour of parallel rather than hierarchical processing. There was no strong
      association between deficits in non-verbal auditory recognition and aphasia or
      the side of lesion.

PMID- 8736572
TI  - Asymmetries in intermanual transfer of maze learning in right- and left-handed
      adults.
AB  - This study examined asymmetries in transfer learning on a finger maze as a
      function of handedness, hand at acquisition and maze orientation at transfer. In
      both handedness groups, right-hand acquisition enhanced opposite hand performance
      on an identical and a vertically reversed maze at transfer, relative to a mirror
      reversed maze; left-hand acquisition, in turn, enhanced opposite hand transfer on
      the spatially reversed mazes relative to the identical maze. The findings suggest
      that different strategies (i.e. verbal versus spatial/motoric) come into play in
      maze learning depending on the hand used at acquisition (right versus left,
      respectively) rather than on overall hand dominance.

PMID- 8736573
TI  - Parallel direction and extent specification of planar reaching arm movements in
      humans.
AB  - The present study was undertaken to clarify further whether the programming of
      direction and extent of the same motor trajectory is accomplished by parallel or
      serial processing channels. We reasoned that if direction and distance are
      independently specified, then the time course of each process should not be
      influenced by the need for simultaneously specifying the other parameter. If
      direction and distance are specified in a serial order, the need to specify two
      parameters rather than only one should prolong the process of response
      specification. For this purpose experiments were run on the same six subjects,
      using our time-response paradigm and the data obtained were compared. To avoid
      any possible effect attributable to the Hick and Hyman law, the number of targets
      was maintained invariant and equal to four. Our major finding is that the time
      course of directional specification of reaching movements is not influenced by
      the need for simultaneously specifying extent. This is consistent with our view
      of parameterization of planning and executing movements, in which the two
      parameters (direction, extent) can be specified in parallel.

PMID- 8736574
TI  - Endotoxin administration induced differential neurochemical activation of the rat
      brain stem nuclei.
AB  - Lipopolisaccharide (LPS) is a potent activator of the immune system, but also
      activates the hypothalamic-pituitary-adrenocortical (HPA) axis and cerebral
      catecholamine systems. In the present study, the effect of peripheral LPS
      administration on catecholaminergic and serotonergic neurotransmission in
      discrete brainstem nuclei was examined. Two hours following systemic
      administration of LPS (1, 10, or 100 micrograms/kg) norepinephrine (NE) content
      in the locus coeruleous (LC) was significantly increased in a dose related
      manner. An increased dopamine (DA) turnover as reflected by the 3,4
      dihydroxyphenylacetic (DOPAC) + Homovanillic acid (HVA)/DA ratio, [DO-PAC +
      HVA]/[DA], was also observed at the LC with the medium and high doses of LPS
      administered. Endotoxin caused the main effects in the nucleus of the tractus
      solitarii (NTS) in which (a) it was found NE content increased in a dose related
      fashion, (b) DA turnover index was elevated with 10 and 100 micrograms/kg LPS
      doses, and (c) levels of serotonin (5-HT) and its catabolite, 5-hydroxyindole-3
      acetic acid (5-HIAA), were also significantly elevated following the injection of
      10 or 100 micrograms/kg LPS. By contrast, a consistent lack of catecholaminergic
      and serotonergic responses to endotoxin treatment was observed at the level of
      midbrain Raphe nuclei (MRN). These results demonstrate that differential
      neurochemical changes may occur in the brainstem region with a rank order of
      activation by LPS that was NTS > LC > MRN, suggesting different neural substrate
      for central effects of peripheral immune activation.

PMID- 8736575
TI  - Effects of the GABAB antagonist CGP 35348 on sleep-wake states, behaviour, and
      spike-wave discharges in old rats.
AB  - The GABAB antagonist CGP 35348 was intraperitoneally given in doses of 100, 300,
      and 900 mg/kg to old rats. These rats were earlier chronically provided with EEG
      and EMG electrodes. Sleep recordings based on visual inspection of EEG and EMG
      recordings were made for 3 h post injection, and spontaneous behaviour in the
      recording cage was additionally observed. With 100 and 300 mg/kg, the drug
      produced an increase in the duration of REM sleep compared to the saline-injected
      control group. The REM sleep latency was correspondingly reduced. Non-REM sleep
      and total sleep duration increased and an s-shaped dose-response relationship was
      found. Explorative behaviour was diminished after injections with 100 and 300
      mg/kg CGP 35348. The number and duration of spike-wave discharges were reduced
      after all doses of CGP 35348 and during all 3 recording hours. The latter
      outcomes confirm the strong suppressive action of this drug on spike-wave
      discharges; these effects have also been reported in models of absence epilepsy.
      The hypnotic properties and especially the increase in REM sleep after the
      administration of CGP 35348 deserve attention considering the paucity of drugs
      which facilitate REM sleep. The discovery of drugs promoting REM sleep might have
      theoretical as well as clinical consequences.

PMID- 8736576
TI  - Effects of glutamate receptor antagonists on posthypoxic myoclonus in rats.
AB  - Male Sprague-Dawley rats developed posthypoxic myoclonus following 10-min cardiac
      arrest and resuscitation. In current studies, roles of N-methyl-D-aspartate
      (NMDA), non-NMDA (a-amino-3-hydroxy-5-methylisoxazole-4-propionate, AMPA, and
      kainate), and metabotropic glutamate receptors in the pathophysiology of
      posthypoxic myoclonus were investigated. Treatments with the competitive or
      noncompetitive NMDA receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid
      (D[-]-AP-5) (ED50: 12.5 mg/kg, i.p.) or MK-801 maleate (ED50: 0.034 mg/kg, i.p.),
      and competitive or noncompetitive non-NMDA (AMPA/kainate) receptor antagonist,
      6,7-dinitroquinoxaline-2,3-dione (DNQX) (ED50: 9.25 nM/5 microliters, i.c.v.) or
      1-(4-ami -nophenyl)-4-methyl-7,8-methylenedioxy -5H-2,3-benzodiazepine
      hydrochloride (GYKI 52466) (ED50: 0.67 mg/kg, IP), significantly decreased
      myoclonus episodes in rats. On the other hand, treatment with the metabotropic
      glutamate receptor antagonist, L(+)-2-amino-3-phosphonopropionic acid (L[+]-AP-3)
      (50 or 500 nM/5 microliters, i.c.v., exerted no significant effect on myoclonus
      scores in posthypoxic rats. These results indicate that activation of NMDA and
      non-NMDA receptors receptors may mediate posthypoxic myoclonus in rats, whereas,
      involvement of metabotropic glutamate receptors needs to be studied further.

PMID- 8736577
TI  - Expression of the beta 1 and beta 2(AMOG) subunits of the Na,K-ATPase in neural
      tissues: cellular and developmental distribution patterns.
AB  - We have used isoform-specific antisera against the Na,K-ATPase beta 1 (SpETb1)
      and beta 2(AMOG) (SpETb2) subunit isoforms in order to establish their specific
      cellular and subcellular localization in several developmental stages of the rat
      central nervous system. Immunocytochemical preparations revealed beta 1 Isoform
      protein in most neural cells, being predominantly located in the soma of neurons
      and astrocytes, with no appreciable developmental variations. In the newborn rat,
      beta 2(AMOG) immunoreactivity was present in cellular processes of astroglia and
      in the somas of neurons and decreasing in intensity with maturation until
      adulthood, where no beta 2 isoform was detected in neurons. The differential
      location of these isoforms, both developmentally and at the cellular level
      suggest a complex regulation of their genes expression and mechanisms of
      subcellular distribution, as well as functional differences.

PMID- 8736578
TI  - Activation of anterior lobe corticotrophs by electroacupuncture or noxious
      stimulation in the anaesthetized rat, as shown by colocalization of Fos protein
      with ACTH and beta-endorphin and increased hormone release.
AB  - A marked expression of the c-fos proto-oncogene has been recently reported in
      cells of the anterior lobe of the pituitary gland in rats subject to
      electroacupuncture or noxious thermal stimulation under pentobarbital
      anaesthesia. The present study was undertaken to identify the activated pituitary
      cells. Following both kinds of stimulation, most Fos-immunoreactive anterior lobe
      cells showed colocalization with adrenocorticotropic hormone or beta-endorphin
      immunoreactivity. No c-fos expression occurred in pituitary cells immunoreactive
      for growth hormone, prolactin, luteinizing hormone, or thyrotropin-stimulating
      hormone. A marked rise of adrenocorticotropic hormone and beta-endorphin
      concentrations occurred in plasma. In the hypothalamus, c-fos expression was
      increased in the mediobasal nuclei-namely, the arcuate nucleus-and in the
      paraventricular nucleus, but more in the former. It is suggested that
      somatosensory noxious input, or the partly noxious input evoked by
      electroacupuncture, activate the hypothalamo-pituitary-adrenocortical axis as in
      common forms of stress, but with a specific activation of the mediobasal
      hypothalamic nuclei and no stimulation of intermediate lobe cells. Opiate release
      from the pituitary gland may contribute to acupuncture analgesia or the intrinsic
      antinociceptive reactions triggered by noxious stimulation.

PMID- 8736579
TI  - Inositol phosphate formation in mice prenatally exposed to drugs: relation to
      muscarinic receptors and postreceptor effects.
AB  - Mice were exposed to phenobarbital or heroin [diacetylmorphine (DAM)] prenatally
      by feeding the mother phenobarbital on gestation day 9-18; DAM was injected into
      the mother on gestation days 9-18. At the age of 50 days, mice exposed to
      phenobarbital or DAM prenatally were examined for long-term biochemical changes
      in the postsynaptic septohippocampal system as measured by alterations in
      formation of the second messenger inositol phosphate (i.p.). A significant
      increase in i.p. formation in response to carbachol was found after prenatal
      exposure to DAM. An increase in i.p. formation in response to 20 mM KCl alone or
      in the additional presence of 10 mM carbachol or 1mM physostigmine was found
      after prenatal exposure to phenobarbital or DAM. In addition, a significant
      increase in IP formation in response to sodium fluoride was found after prenatal
      exposure to phenobarbital or DAM. It is suggested that an increase in G-protein
      activation and in the second messenger formation accompanies the early drug
      induced upregulation of the muscarinic receptors found in our previous studies.

PMID- 8736580
TI  - Sexual dimorphism of GABAA receptor levels in subcortical brain regions of a
      woodland rodent (Apodemus sylvaticus).
AB  - This is the first report of quantitative autoradiography results showing sex
      differences of GABAA receptor levels in brain regions of a wild rodent (wood
      mouse, Apodemus sylvaticus) living in its natural habitat. The labeling of this
      GABAergic site with its specific high affinity radioligand [3H] muscimol provided
      a heterogeneous and dimorphic binding pattern in some of the neural centers. In
      the female, higher (> or = 50 < or = 65%) to moderately higher (< 50%) binding
      levels than in the male, even after correction of the specific binding values
      using the calculated quenching coefficients, were observed in the substantia
      nigra pars reticulata and ventral lateral thalamic nucleus, brain centers that
      are relays of motor circuits. In the male, on the other hand, a higher level was
      only obtained in the caudateputamen. Relays of the stria terminalis-hypothalamic
      central gray pathway such as the bed nucleus of the stria terminalis, the pontine
      central gray and the ventromedial hypothalamic nucleus, were among the other
      female brain areas with an extremely higher (> 65%) to higher and moderately
      higher binding activity than in the male. From the saturation analyses, it
      appeared that the binding differences were mainly due to Bmax variations,
      although closer examinations revealed that changes in the KD might have also
      accounted for [3H] muscimol binding differences, as shown by the high KD and Bmax
      values in the bed nucleus of the stria terminalis, the substantia nigra pars
      reticulata and the pontine central gray of the female wood mouse. These findings
      suggest that the dimorphic binding activity of GABAA receptors in the above brain
      regions might be involved in neuronal circuitry mechanisms related to sex
      specific social behaviors in rodents living in their natural environmental
      conditions.

PMID- 8736581
TI  - Median eminence corticotrophin-releasing hormone content following prenatal
      stress and neonatal handling.
AB  - Neonatal handling produces enduring changes in hypothalamic-pituitary-adrenal
      (HPA) axis activation in response to acute stress presentation. Handled rats
      display reduced HPA activity in response to stress, which is associated with
      increased hippocampal glucocorticoid receptor densities and decreased median
      eminence corticotrophin-releasing hormone (CRH) content. Prenatal stress (PS)
      also has long-term consequences on HPA responsivity to stress and related
      behavioral profiles. On the basis of earlier behavioral data suggesting that PS
      contributed to the expression of handled responses, we investigated how PS and
      handling might interact to affect median eminence CRH content. Groups of
      prenatally stressed rats and controls were subjected to a handling procedure or
      left undisturbed. Adult rats were killed and median eminence CRH levels were
      assayed as well as plasma corticosterone (CORT). PS and handling did not affect
      CRH content; however, handled plus PS rats exhibited significantly reduced CRH
      levels. Handling decreased plasma CORT concentrations, an effect that was absent
      in the PS rats. We contend that PS can modulate an animal's sensitivity to later
      environmental manipulations while producing minimal effects on its own.
      Researchers interested in early environmental conditions and later physiologic
      and behavioral responses should monitor their subjects' gestational history.

PMID- 8736582
TI  - Inhibition by MK-801 of cocaine-induced sensitization, conditioned place
      preference, and dopamine-receptor supersensitivity in mice.
AB  - Repeated administration of cocaine led to increases in ambulation-accelerating
      activity (sensitization) and conditioned place preference (CPP). Dopamine (DA)
      receptor supersensitivity was also developed in cocaine-induced sensitized and
      CPP mice. An N-methyl-D-aspartate (NMDA)-receptor antagonist, MK-801, blocked
      simultaneously developments of cocaine-induced behavioral sensitization, CPP, and
      DA-receptor supersensitivity. Furthermore, MK-801 inhibited a apomorphine-induced
      striatal dopaminergic action: climbing behavior. These results suggest that the
      cocaine-induced dopaminergic behaviors such as sensitization to ambulatory
      activity and CPP may be produced via activation of the NMDA receptor. The
      development of postsynaptic DA-receptor supersensitivity may be an underlying
      common mechanism that mediates cocaine-induced behavioral sensitization and CPP.

PMID- 8736583
TI  - Morphologic analysis of rat retino-collicular neuron terminals containing
      monoamine oxidase.
AB  - The retino-collicular neuron terminals containing type A monoamine oxidase (MAO
      A) in the stratum griseum superficiale of the rat superior colliculus were
      analyzed to provide a morphologic basis for the physiologic role of these neurons
      in the visual pathway. A computer-assisted, three-dimensional reconstruction of
      the terminal complex associated with the MAO-A-positive terminals was performed.
      MAO-A-positive terminals originated in the retina and terminated in the stratum
      griseum superficiale. This was confirmed by tract tracing and enucleation
      experiments. The terminals were densely grouped in clusters of irregularly shaped
      swellings. Electron microscopy revealed that the MAO-A-positive terminals were
      located in a glomerulus-like structure. In this terminal complex, a significant
      proportion of the axonal profiles (42.96%) synapsed with the MAO-A-positive
      terminals. Most of the profiles (24.16%) resembled presynaptic dendrites, which
      represent intermediate elements between the retinal terminals and conventional
      dendrites. Unlike the glomerulus in the dorsal lateral geniculate body, the MAO-A
      positive terminal swellings were not located in the central part of the terminal
      complex. The terminals had an irregular shape and were located in the complex.
      The terminal complex was partially ensheathed by glial processes. Furthermore,
      the membrane surfaces exhibiting synaptic specializations were very small
      compared with the total surface of the terminal swellings. The membrane length of
      the synaptic specialization was 5.38% of the total perimeter of the MAO-A
      positive terminals.

PMID- 8736584
TI  - Efferent projections of the retrorubral nucleus to the substantia nigra and
      ventral tegmental area in cats as shown by anterograde tracing.
AB  - The aim of the present study was to determine whether the retrorubral nucleus
      projects to the dopaminergic nuclei in the ventral midbrain of the cat. For this
      purpose, injections of biotinylated dextran-amine or Phaseolus vulgaris
      leucoagglutinin were placed into the retrorubral nucleus under stereotaxic
      guidance. The tracers were visualized by means of (immuno) histochemical
      procedures. In addition, tyrosine hydroxylase immunohistochemistry was used to
      evaluate the location of the injection sites and the distribution of the
      anterogradely labeled fibers. Both tracers reveal the same topography of labeled
      fibers in the ventral mesencephalon. Labeled fibers with varicosities were found
      ipsilaterally in the substantia nigra pars compacta, the substantia nigra pars
      lateralis, the ventral tegmental area and, contralaterally, in the substantia
      nigra pars compacta, the ventral tegmental area, and the retrorubral nucleus. A
      considerable number of labeled axons with varicosities were observed to be
      wrapped around the dendrites and perikarya of tyrosine hydroxylase-positive
      neurons in these areas. The present results are discussed in view of the possible
      role of the A8 dopaminergic cell group in the coordination of A9 nigrostriatal
      and A10 mesolimbic systems, as well as in the progressive pathology seen in
      patients suffering from Parkinson's disease.

PMID- 8736585
TI  - Ischemic tolerance to memory impairment associated with hippocampal neuronal
      damage after transient cerebral ischemia in rats.
AB  - When rats were trained preoperatively with a three-panel runway task and were
      then exposed to 10-min ischemia by the method of 4-vessel occlusion, they showed
      no increase in the number of errors (attempts to pass through two incorrect
      panels of the three panel-gates at four choice points), having normal retention
      of memory performance learned before the ischemic insult. Next, we investigated
      the abilities of ischemic rats to acquire the three-panel runway task and to
      learn a subsequent reversal task, where the correct panel-gate locations were
      changed. Rats with 5-min ischemia exhibited performance as good as that of
      control rats, but rats exposed to 10- and 20-min ischemia showed more errors than
      control rats during 10 acquisition sessions and 5 subsequent reversal sessions,
      each of which (consisting of 6 trials) was given once a day. Marked neuronal
      degeneration was observed in the hippocampal CA1 sector from the rats with 10-
      and 20-min ischemia. Exposure to sublethal 5-min ischemia followed by 10-min
      ischemia at a 2-h interval had no effect on either the memory impairment during
      acquisition and reversal tests or the hippocampal CA1 damage. When rats were
      exposed to 5-min ischemia 2 days before lethal 10-min ischemia, they showed
      acquisition and subsequent reversal learning as good as that of control rats.
      Preconditioning with sublethal 5-min ischemia followed by 2 days of reperfusion
      also prevented the neuronal destruction of the hippocampal CA1 sector induced by
      10-min ischemia. These findings suggest that postischemic hippocampal CA1
      neuronal damage does not affect retention of spatial memory acquired before
      ischemia, but produces a significant impairment of acquisition and subsequent
      reversal learning. The present results also demonstrate that preconditioning with
      sublethal ischemia can develop tolerance to subsequent lethal ischemia to prevent
      the learning impairment related to the hippocampal CA1 neuronal damage.

PMID- 8736586
TI  - Association of serum cholesterol and triglyceride levels with agitation and
      cognitive function in a geropsychiatry unit.
AB  - Several studies have reported an association between aggression and cholesterol
      levels. The purpose of this study was to investigate the relationship of serum
      cholesterol and triglyceride levels with aggression and cognitive function in
      elderly inpatients. One hundred ten patients consecutively admitted to the
      Geriatric Psychiatry inpatient unit at Houston's Veterans Affairs Hospital
      received comprehensive evaluations by a multidisciplinary team. Fasting serum
      cholesterol and triglyceride levels were obtained within 3 days of admission. In
      addition, two geriatric psychiatrists administered the Mini-Mental State
      Examination (MMSE) and the Cohen-Mansfield Agitation Inventory (CMAI).
      Correlation coefficients were calculated between lipid levels, CMAI total and
      subscale scores, and MMSE scores. Multiple linear-regression analyses were done
      to further investigate the relation between lipid concentrations and various
      confounders. We found no significant correlation between serum triglyceride
      levels and MMSE, CMAI total, and CMAI factor scores. In addition, we found a
      significant positive correlation between serum cholesterol levels and physical
      nonaggressive behavior, and a significant negative correlation between serum
      cholesterol levels and MMSE scores. We found no relationship between aggressive
      behavior and serum cholesterol or triglyceride levels. However, an association
      between high cholesterol levels and agitation exists, which may be mediated by
      the association between high cholesterol levels and impaired cognition.

PMID- 8736587
TI  - Psychiatric illnesses in the elderly: a review.
AB  - Neuropsychiatric disorders in the elderly, such as dementia, depression, anxiety,
      and psychosis, may occur alone or in combination with neurologic or medical
      illness. Geriatricians must be familiar not only with diagnostic issues but also
      with treatment options and medication-induced alterations in mental status.

PMID- 8736588
TI  - Effects of passive body heating on the sleep of older female insomniacs.
AB  - The purpose of this study was to evaluate passive body heating (PBH) as a
      treatment for insomnia in older adults. Polysomnographic recordings of older
      adults routinely show an increase in sleep fragmentation and a substantial
      decrease in slow-wave sleep (SWS) consistent with complaints of "lighter" more
      disturbed sleep. An increase in body temperature in young adults early in the
      evening by way of PBH has been shown to produce an increase in SWS in the early
      part of the sleep period. In a crossover design, nine female insomniacs (aged 60
      72 yr) participated in two consecutive nights of PBH, involving hot (40-40.5
      degrees C) and luke-warm (37.5-38.5 degrees C) baths 1.5 hours before bedtime.
      Significant improvement in sleep continuity and a trend toward an increase in SWS
      occurred after hot baths. Results of subjective measures showed that subjects
      experienced significantly "deeper" and more restful sleep after hot baths. In
      addition, hot baths resulted in a significant delay of temperature nadir in
      comparison to baseline nights.

PMID- 8736589
TI  - Management of the prescription-drug-dependent adult: case of meprobamate abuse
      and its treatment.
AB  - Misuse of prescription drugs in the elderly can be a serious problem that is
      difficult to manage. Prescriptions for non-narcotic central nervous system (CNS)
      depressants (e.g., anxiolytics and sedative-hypnotics) are commonly written, and
      their use is associated with severe intoxication and withdrawal effects. The
      presence of comorbid psychiatric conditions (e.g., depression or panic disorder),
      for which these agents are prescribed frequently, complicates the clinical
      picture. This paper, using case examples of meprobamate abuse, describes how
      physicians can recognize, manage, and treat a patient who is abusing a non
      narcotic CNS depressant.

PMID- 8736590
TI  - Failure to record delirium as a complication of intra-aortic balloon pump
      treatment: a retrospective study.
AB  - This study was conducted to determine whether or not diagnosis and treatment of
      delirium among patients treated with the intra-aortic balloon pump (IABP)
      correlates with the recording of this complication on discharge records. Since
      prior episodes of delirium are one of the few clear risk factors for future
      episodes of delirium, accurate recording of delirium on the discharge summary and
      list of discharge diagnoses is useful to clinicians. A retrospective review of
      the charts of all patients (N = 198) who underwent placement of an IABP during
      1988; assessment of the type and frequency of medical and neuropsychiatric
      complications during IABP treatment; and comparison of chart review findings with
      the Massachusetts General Hospital's computer-generated lists of discharge
      diagnoses for the same IABP-treated patients was completed. Only 12% of patients
      diagnosed and treated for delirium had delirium recorded as a discharge
      diagnosis. In contrast, 44% and 52% of patients who had been diagnosed and
      treated for cerebrovascular accident and pneumonia, respectively, had these
      diagnoses recorded among the discharge diagnoses. Receiving a discharge diagnosis
      of organic brain syndrome increased the likelihood that delirium was recorded as
      a discharge diagnosis. Delirium is underdiagnosed as a complication associated
      with IABP-treatment and is under-reported on the list of discharge diagnoses,
      even when it is diagnosed. Further study is warranted to determine if making the
      diagnosis of delirium during a patient's hospital course and recording it is a
      complication at the time of discharge is translated into a higher level of
      preparedness by physicians during subsequent hospitalizations.

PMID- 8736591
TI  - Chronic subdural hematoma in the elderly: a case report.
AB  - A previously healthy 82-year-old male presented with depressive and paranoid
      symptoms of 3 months' duration. Physical examination and cognitive functions were
      normal. Poor response to treatment and continuing weight loss lead to medical
      investigations that ultimately showed a large, left frontoparietal, chronic
      subdural hematoma. Following drainage, the patient showed some improvement in
      paranoid features but still required pharmacologic treatment for depression. The
      psychiatric features of chronic subdural hematoma as well as the management of
      this neurologic condition in the elderly patient are reviewed and discussed.

PMID- 8736592
TI  - Neurobiology of disruptive nocturnal behavior.

PMID- 8736593
TI  - An analysis of lymph node DNA for possible bacterial agents of cat-scratch
      disease.
AB  - Recent investigations have implicated Afipia felis and Rochalimaea henselae as
      possible agents of cat-scratch disease (CSD). We studied lymph nodes with
      necrotizing granulomas characteristic of CSD for A. felis and R. henselae DNA so
      that the relationship of these organisms to lymph nodes with necrotizing
      granulomas of unknown etiology might be better defined. We examined formalin
      fixed, paraffin-embedded lymph node biopsies with necrotizing granulomas
      suggestive of CSD from 28 children obtained over the last 10 years. None had
      identifiable bacteria, fungi, or acid-fast organisms on routine staining.
      Pleomorphic bacillary structures consistent with the CSD bacillus were seen with
      the Steiner stain in 17 cases. We performed the polymerase chain reaction (PCR)
      on the extracted lymph node DNA with DNA primers for these organisms after
      demonstrating the presence of amplifiable DNA with c-K-Ras primers. R. henselae
      was identified in two samples. A. felis DNA was found in just one specimen. These
      putative CSD bacteria are infrequently associated with necrotizing granulomas
      using standard PCR techniques. It is possible that some of the patients did not
      have clinical CSD. The preservation of DNA or numbers of bacteria in the
      extracted sections may be inadequate for demonstration by DNA amplification
      methods. These bacilli may be responsible for a small proportion of these
      characteristic lesions of unknown etiology, or the typical CSD histology,
      including the presence of pleomorphic bacillary structures, may be nonspecific.

PMID- 8736594
TI  - Outflow tract abnormalities in atrioventricular canal malformations.
AB  - Atrioventricular canal malformations are commonly regarded as being arrests of
      development of normal cardiac septation since their morphology strongly resembles
      the normal heart of Carnegie stages 14 through 18. Similarly, the spectrum of
      outflow tract abnormalities, which includes truncus arteriosus, transposition of
      the great arteries, double outlet right ventricle, and tetralogy of Fallot, has
      been interpreted as a developmental arrest because these malformations resemble
      the normal embryonic outflow tract in Carnegie stages 14 through 18,
      respectively. The causes of the developmental arrests in these two classes of
      malformations are unknown. Observation of an unusual autopsy case with features
      of both atrioventricular canal defect and tetralogy of Fallot prompted us to
      review the outflow tract morphology in 38 hearts with an atrioventricular canal
      malformation and two semilunar valves to determine if there was evidence to
      support the idea that both conditions may have the same pathogenesis. In all 38
      hearts there was fibrous continuity between an anterior mitral leaflet and an
      aortic valve, which by anatomic definition means that no case had truncus
      arteriosus, transposition of the great arteries, or double outlet right
      ventricle. There were three cases with coarctation of the aorta, a lesion which
      arises when blood flow in the pulmonary trunk exceeds aortic flow during early
      development. There were four cases with pulmonary to aortic valve caliber ratios
      similar to those found in tetralogy of Fallot but the aortic-to-pulmonary valve
      angle relative to the heart base ranged over the full spectrum of angles seen in
      normal hearts and those with tetralogy of Fallot. Furthermore, this angle showed
      the same range of values for partial and complete canal defects, and did not
      correlate with patient age or ratio of pulmonary to aortic valve caliber. We
      conclude that the pathogenesis of the spectrum of outflow tract developmental
      arrests is different from that of atrioventricular canal malformations.

PMID- 8736595
TI  - Hypothesis: pathogenesis of skip areas in long-segment Hirschsprung's disease.
AB  - The existence of skip areas in a subset of patients with long-segment
      Hirschsprung's disease (LSHD) is a rare phenomenon that poses practical and
      theoretical challenges. In this paper, three new cases are described and compared
      with preceding reports in the medical literature. In addition, an analogous
      distribution of ganglion cell precursors is reported in the developing large
      intestines of murine embryos, homozygous for the lethal spotted (ls) allele. In
      ls/ls embryos, which were destined to have "classic" short-segment aganglionosis
      coli, a transient phase was observed in which ganglion cells were present in the
      middle colon, but absent from the cecum and distal large intestine. This "skip
      area" is attributed to an extramural phase of neuroblast migration which is
      unique to the colon. Persistence of an abnormal pattern of neuroblast migration,
      similar to that observed transiently in ls/ls embryos, is invoked as an
      explanation for skip areas in humans with LSHD.

PMID- 8736596
TI  - Agenesis of the ductus venosus and its correlation to hydrops fetalis and the
      fetal hepatic circulation: case reports and review of the literature.
AB  - Under normal conditions about 50% of the placental venous return bypasses the
      liver through the ductus venosus. This blood flow is preferentially directed
      toward the foramen ovale and provides optimum oxygenation to the fetal heart and
      brain. Absence of the ductus venosus is a rare vascular anomaly, the significance
      of which has been disputed. We distinguish the pattern in which the liver is
      entirely bypassed, a manifestation of a fundamental malformation in the umbilical
      venous system, from the pattern in which the ductus venosus is absent despite a
      normal course of the umbilical vein. We review the literature regarding the
      latter and report eight new cases. Three of the four previously reported cases
      showed associated malformations and two of them suffered from portal congestion
      and hydrops. Among our eight cases three showed severe malformations in the
      cardiovascular system. Three cases presented themselves with hydrops fetalis and
      disturbance in the portal circulation, and two cases expressed signs of
      intrauterine asphyxia. The absence of the ductus venosus might be a minor
      vascular maldevelopment resulting in an early disturbance in the portal
      circulation. Our findings suggest that this anomaly might induce hydrops fetalis.

PMID- 8736597
TI  - Adrenocortical heterotopia in the placenta.
AB  - We report two cases of term third-trimester placentas with microscopic nodules of
      cells histopathologically identical to adrenocortical tissue. Adrenocortical
      tissue within the placenta is exceedingly rare, with only one previous case
      reported. We discuss the possible histogenesis of this entity.

PMID- 8736598
TI  - Neu-Laxova syndrome: pathological evaluation of a fetus and review of the
      literature.
AB  - Neu-Laxova syndrome is a rare autosomal recessive disorder characterized by
      ichthyosis, intrauterine growth retardation, microcephaly, short neck, central
      nervous system abnormalities, hypoplastic or atelectatic lungs, limb deformities,
      edema, polyhydramnios, and short umbilical cord. Abnormal facial features include
      sloping forehead, hypertelorism, severe ectropion, proptosis, malformed ears,
      flat nose, and micrognathia. A necropsy study of a male infant with Neu-Laxova
      syndrome is described. Cleft palate and ambiguous external genitalia were present
      in addition to anomalies characteristic of Neu-Laxova syndrome. The clinical
      manifestations are compared with those of the 40 previously reported cases.

PMID- 8736599
TI  - Asynchronous pulmonary hyperplasia associated with tracheal atresia: pathologic
      and prenatal sonographic findings.
AB  - We describe a case of pulmonary hyperplasia associated with tracheal atresia and
      a complete obstruction to the egress of pulmonary secretions. In classical
      pulmonary hyperplasia associated with cartilagenous laryngeal atresia and a
      persistent pharyngotracheal duct, the histologic appearance of the lungs is
      normal but exhibits "synchronous" hypermaturity. The histologic pattern in our
      case is much less mature, resembles CAM type III, and exhibits "asynchronous"
      development. We suggest that these histologic patterns be distinguished and that
      pulmonary hyperplasia is probably underrecognized and not nearly as rare as
      previously thought.

PMID- 8736600
TI  - Intraairway Feulgen-positive bodies in hyaline membrane disease of the newborn.
AB  - In reviewing cases of hyaline membrane disease of the newborn (HMD) we have been
      struck by the occurrence of dense basophilic bodies within the airways. To
      further examine this phenomenon we reviewed lung histology from 246 consecutive
      stillborns and liveborns 24 hours or less of age autopsied at The Johns Hopkins
      Hospital. Cases with autolysis or major malformations were excluded. We found the
      basophilic bodies in 61 (71%) of 87 infants with HMD. The material forming the
      bodies was Feulgen-positive and derived from necrotic respiratory epithelial
      cells. Pyknotic nuclei were extruded from necrotic cells and fused to form the
      bodies some of which reached a size of over 50 microns in maximum dimension.
      Among the 159 cases without HMD, only 13, all of which were among 81 cases of
      fetal pneumonia, showed small, 2-5 microns in diameter, intraairway Feulgen
      positive bodies. The bodies in these cases of fetal pneumonia were derived from
      disintegrating leukocytes. The study shows that the formation of intraairway
      Feulgen-positive bodies derived from necrotic epithelial cells is a common
      finding in infants dying with HMD during the first day of life. The early
      development and frequent occurrence of the bodies lends support to the idea that
      respiratory epithelial cell necrosis is the cause of HMD of the newborn.

PMID- 8736601
TI  - Duplication of 9P and hyperplasia of the choroid plexus: a pathologic,
      radiologic, and molecular cytogenetics study.
AB  - Duplication of the short arm of chromosome 9 is a rare constitutional
      abnormality, and the presence of pathologically confirmed hyperplasia of the
      choroid plexus in one of two cases, and a choroid plexus papilloma in another,
      raises the possibility of a relationship between the 9p abnormality and abnormal
      growth of the choroid plexus. Molecular cytogenetic analysis using fluorescence
      in situ hybridization was used for detection of chromosome 9-derived material in
      various formalin-fixed choroid plexus abnormalities. Extra copies of chromosome 9
      derived material was found in the hyperplastic choroid plexus and in a choroid
      plexus carcinoma. These findings suggest that there may be an association between
      duplication of chromosome 9 material and abnormal development of the choroid
      plexus.

PMID- 8736602
TI  - Fetal parvovirus B19 infection and liver disease of antenatal onset in an infant
      with Ebstein's anomaly.
AB  - Fetal parvovirus B19 infection has been reported in association with hydrops and
      fetal demise, myocarditis, and congenital anomalies, as well as with normal
      outcome of pregnancy. One infant with liver disease of fetal onset associated
      with parvovirus B19 infection has been described. We have seen another such
      infant, in whom marked siderosis of the liver suggested accelerated destruction
      of erythrocytes and portal tract fibrosis with proliferation of bile ducts
      suggested intrauterine infection. Viral cytopathic effects were not seen.
      Maternal serum obtained postpartum contained IgM class antibodies against
      parvovirus B19, and parvovirus B19 nucleic acid sequences were identified in the
      infant's liver by polymerase chain reaction studies. We propose that recognition
      of this combination of siderosis with fibrosis and bile duct proliferation will
      permit identification of cases of fetal parvovirus B19 infection.

PMID- 8736604
TI  - Bone invasion by a recurrent digital fibroma of infancy in a child with Beckwith
      Wiedemann syndrome.
AB  - We describe a child with features of the Beckwith-Wiedemann syndrome with
      congenital recurrent digital fibroma of infancy that extended into and replaced
      the marrow of the terminal phalynx of the little finger. Digital fibromas of
      infancy have not previously been associated with either Beckwith-Wiedemann
      syndrome or invasion into underlying bone.

PMID- 8736603
TI  - Pathology of chronic herpes infection associated with seizure disorder: a report
      of two cases with tissue detection of herpes simplex virus 1 by the polymerase
      chain reaction.
AB  - Although uncommon, the association of chronic encephalitis with epilepsy is well
      recognized. While a viral etiology has been suspected based on the morphology, to
      date no virus has been successfully cultured from the brain in patients with
      Rasmussen's encephalitis. We describe the pathologic findings and report the
      detection of herpes simplex virus 1 (HSV1) in the brain in two patients who
      presented primarily with intractable seizures. In the first patient, an
      intrauterine infection was suspected as the underlying basis for the seizure
      disorder and the extensive cerebral calcification and gliosis. The second patient
      (with presumed HSV1 encephalitis at age 7 months) underwent a temporal lobectomy
      for medically refractory seizures at the age of 3 years and pathologic
      examination revealed a chronic encephalitis. While immunohistochemical,
      ultrastructural, and culture studies were negative for viral pathogens, molecular
      analysis by the polymerase chain reaction (PCR) revealed HSV1 DNA sequences in
      both cases. Thus our cases represent two examples of chronic encephalitis
      associated with a seizure disorder, where a definitive viral etiology was
      documented by PCR.

PMID- 8736605
TI  - Hepatic vascular malformation.

PMID- 8736606
TI  - Malignant germ cell tumor and urticaria pigmentosa.

PMID- 8736608
TI  - Olivopontocerebellar atrophy in carbohydrate-deficient glycoprotein syndrome.

PMID- 8736607
TI  - Atypical juvenile xanthogranuloma.

PMID- 8736609
TI  - Familial right ventricular dysplasia (cardiomyopathy).

PMID- 8736610
TI  - Lethal Dowling-Meara-type epidermolysis bullosa simplex in a young infant.

PMID- 8736611
TI  - Hepatic angiomyolipoma in childhood: association with tuberous sclerosis.

PMID- 8736612
TI  - Congenital tracheal anomalies.

PMID- 8736613
TI  - Cervical teratomas.

PMID- 8736615
TI  - Drug therapy of non-insulin-dependent diabetes mellitus in the elderly.
AB  - Non-insulin-dependent diabetes (NIDDM) is a common problem in the elderly. The
      discovery of several classes of oral antidiabetic agents has increased the
      prospects of achieving better control of hyperglycaemia with reduced risk of
      severe adverse events. Some of these agents, such as acarbose or miglitol, do not
      cause hypoglycaemia and act locally in the gut. As such they are safer agents. On
      the other hand, the low cost of some sulphonylurea agents and a once or twice
      daily administration schedule make them an attractive option. Metformin appears
      to be especially useful in obese insulin-resistant patients with NIDDM. However,
      obesity is not as much of a problem in the elderly as it is in middle-aged
      patients, and contraindications to the use of metformin are common in the
      elderly. The use of a combination of 2 or 3 oral antidiabetic agents to delay the
      need for insulin therapy is now possible. The long term effects of this approach
      are not known and the cost of polypharmacy is of concern.

PMID- 8736614
TI  - Adverse effects of antipsychotic agents. Do newer agents offer advantages?
AB  - Although antipsychotic drugs are effective in treating the so-called positive
      features of schizophrenia, between one-quarter and one-third of patients respond
      poorly. Furthermore, the incidence of adverse effects is high, especially those
      reflecting disruption of extrapyramidal function, and is a major source of non
      compliance. There is a clear need for new compounds that are more efficacious
      and/or better tolerated. Until recently, the classical dopamine hypothesis, with
      its emphasis on D2 blockade as the key mechanism of antipsychotic action,
      dominated drug development, though the emphasis is now shifting. Three 'new'
      antipsychotics have reached the international market in the past 5 years-the
      newly rehabilitated clozapine and the genuinely new remoxipride and risperidone.
      Claims of enhanced tolerability have been made for each of these, but as none is
      free from adverse effects, their place in treatment can only be meaningfully
      established in relation to the efficacy of each in different clinical situations.
      Clozapine has an extensive profile of general, nonhaematological adverse effects
      which is slightly different in emphasis from, but comparable in incidence to,
      that of chlorpromazine. There is a 0.8% risk of agranulocytosis in the first year
      of exposure, which can be fatal, though the boundary separating it from other
      (especially phenothiazine) antipsychotics in this regard is becoming increasingly
      blurred. It has a clearly diminished liability to cause extrapyramidal adverse
      effects. Its proven efficacy in operationally defined treatment-resistant
      schizophrenia and in patients intolerant to the extrapyramidal adverse effects of
      standard drugs establishes its credentials for advantage in these groups. There
      is on present evidence, however, only a hint of enhanced efficacy in acute
      schizophrenia: this requires further investigation. Open maintenance studies
      provide impressive data on long term outcome, especially in terms of quality-of
      life parameters, but this issue requires to be addressed in blind, randomised
      trials. Until such additional information is forthcoming the risks and consequent
      costs would not justify extension of its use. The evidence to date is that
      reported benefits in so-called negative features probably reflect its favourable
      neurological profile. While the advantages of clozapine are undoubted, they
      remain as yet restricted to selected patient groups. Remoxipride has a good
      general tolerability profile, its special strength being its low sedative effect.
      However, its reported association with aplastic anaemia has severely restricted
      its use, and regular haematological monitoring is required. Although remoxipride
      appears to have a lower liability to produce extrapyramidal adverse effects than
      the high potency haloperidol, its benefits relative to other low potency
      compounds in this regard remain unproven. The only obvious situation in which its
      risks and consequent costs would be justified would seem to be patients with
      established compliance problems as a result of intrusive sedation with standard
      drugs. The position of other benzamides such as raclopride and amisulpride
      remains to be established. Risperidone, perhaps from its antiadrenergic actions,
      has more in the way of cardiovascular adverse effects than haloperidol, though
      these can be obviated by graded early exposure. It may also be associated with
      greater weight gain. Otherwise it appears to be well tolerated. In comparison
      with haloperidol, it appears to be associated with a lower prevalence of acute
      extrapyramidal adverse effects in dosages < or = 10 mg/day, the most potentially
      important component of which is its reportedly insignificant likelihood of
      promoting akathisia. These conclusions emerge from comparisons with haloperidol
      in doses many might consider somewhat high. The question of the advantage of
      risperidone over low or milligram-equivalent haloperidol regimens remains
      open.(ABSTRACT TRUNCATED)

PMID- 8736616
TI  - The thrombocytopenic purpuras. Recognition and management.
AB  - Idiopathic thrombocytopenic purpura (ITP) and thrombotic thrombocytopenic purpura
      (TTP), are distinct entities. ITP is a relatively common autoimmune disorder
      typically manifesting with isolated thrombocytopenia. The acute form, more common
      in children, is a self-limiting, often post-viral disease. Therapy, if indicated,
      usually consists of a brief course of steroids or intravenous IgG. Chronic ITP,
      more common in adults, rarely remits spontaneously. Most patients respond
      initially to steroids, but generally the disease relapses when steroids are
      tapered. Splenectomy offers a 70% chance of cure. A variety of treatment options
      exist for patients not responding to splenectomy. The treating physician must
      choose the most effective and least toxic treatment for the individual patient.
      TTP is a rare, often life-threatening, multisystem disease of unknown aetiology.
      Its hallmark is widespread occlusion of the microcirculation by platelet
      aggregates. The clinical symptoms usually respond dramatically to plasma exchange
      therapy. Steroids, antiplatelet agents and vincristine may also be useful.
      Splenectomy should be considered in patients with multiple relapses. More
      specific therapy awaits a fuller understanding of the pathogenesis of this
      disease.

PMID- 8736617
TI  - Diagnosis and drug therapy of prolactinoma.
AB  - A prolactin-secreting pituitary tumour is the most frequent cause of
      hyperprolactinaemia that commonly occurs in clinical practice. Prolactinomas
      occur more frequently in women than in men and may differ in size, invasive
      growth and secretory activity. At presentation, macroadenomas are more frequently
      diagnosed in men. Specific immunohistochemical stains are necessary to prove the
      presence of prolactin in the tumour cells. The main investigations in the
      diagnosis of a prolactin-secreting adenoma are hormonal and radiological. As
      prolactin is a pulsatile hormone, it is a general rule to obtain several blood
      samples by taking a single sample on 3 separate days or 3 sequential samples
      (every 30 minutes) in restful conditions. Prolactin levels of 100 to 200
      micrograms/L are commonly considered diagnostic for the presence of a
      prolactinoma; however, prolactinoma cannot be excluded in the presence of lower
      levels, and prolactin levels > 100 micrograms/L are present in some patients with
      idiopathic hyperprolactinaemia. Several dynamic function tests have been proposed
      to differentiate idiopathic from tumorous hyperprolactinaemia. Although they
      could be used for group discrimination, these tests cannot be used for individual
      patients. To differentiate between a prolactinoma and a pseudoprolactinoma,
      thyrotrophin response to a dopamine receptor antagonist may be used, as only
      prolactinomas may have an increased response. A short course of dopaminergic
      drugs may also be of some help, as in macroprolactinomas only a shrinkage may be
      observed. After hyperprolactinaemia is confirmed, imaging with computerised
      tomography (CT) and magnetic resonance imaging (MRI) are necessary to define the
      presence of a lesion compatible with a pituitary tumour. There is now a general
      agreement that medical therapy is of first choice in patients with prolactinomas.
      Bromocriptine, the most common drug used in this condition, is a semisynthetic
      ergot alkaloid that directly stimulates specific pituitary cell membrane dopamine
      D2 receptors and inhibits prolactin synthesis and secretion. In most patients, a
      reduction or normalisation of prolactin levels is usually observed, together with
      the disappearance or improvement of clinical symptoms. The sensitivity to
      bromocriptine is variable and patients may need different dose of the drug.
      Bromocriptine is also able to shrink the tumour in most patients; however, a few
      reports of disease progression during therapy have been described. The need for
      close follow-up, including prolactin levels and CT or MRI studies, is therefore
      emphasised. Bromocriptine is conventionally given in 2 or 3 daily doses; however,
      a single evening dose has been shown to be equally effective. Bromocriptine is
      usually well tolerated by the majority of patients; some adverse effects (nausea,
      vomiting, postural hypotension) may be initially present, but they usually wear
      off in time. To prevent such adverse effects it is advisable to start treatment
      with a low dose during the evening meal and gradually increase the dose over days
      or weeks. A few patients are unable to tolerate oral bromocriptine, so different
      formulations of bromocriptine or alternative dopamine agonist drugs (lisuride,
      terguride, metergoline, dihydroergocryptine, quinagolide, cabergoline, pergolide)
      have been proposed. Of particular clinical relevance because of their good
      tolerability and sustained activity are cabergoline and quinagolide. Particular
      attention should be paid to pregnancy in prolactinoma patients, as tumour
      enlargement has been reported. As the risk for this occurrence is low in patients
      with microprolactinoma, there is a general agreement that the drug can be stopped
      once pregnancy is diagnosed. In patients with macroprolactinoma the risk of
      tumour enlargement is higher. Therefore, primary therapy with bromocriptine until
      the tumour has shrank is suggested before pregnancy is attempted. Bromocriptine
      should be stopped as soon as pregnancy is confirmed, but re

PMID- 8736618
TI  - Practical guidelines for the treatment of cholera.
AB  - Cholera is a dramatic clinical illness that requires rapid diagnosis and
      aggressive therapy. Clinical signs and symptoms of mild, moderate and severe
      dehydration must be determined, before beginning fluid therapy. Fluid therapy has
      2 phases: rehydration (first 3 to 4 hours to correct deficits) and maintenance
      (to match continuing losses). The route and speed of fluid administration will
      depend on the degree of dehydration. Patients with severe dehydration should be
      treated intravenously, as should those patients who do not tolerate oral
      rehydration solution (ORS). Ringer's lactate is the preferred intravenous
      solution, although normal saline may be used along with ORS. For most patients
      with cholera, an ORS using one of the higher sodium-containing solutions and
      plain water optimally provide the fluid and salt needed. Close monitoring of
      intake, outputs and hydration status should be performed for all patients.
      Antimicrobial therapy should be given to moderately and severely ill patients in
      order to decrease the volume of fluids lost and to shorten the period of
      excretion of vibrios.

PMID- 8736619
TI  - Ebrotidine.
AB  - Ebrotidine is the first of a new generation of H2 receptor antagonists with
      gastroprotective activity It stimulates epithelial cell proliferative activity
      and produces beneficial physicochemical changes in the gastric mucus that
      contribute to its gastro-protective action against ethanol-, aspirin- or stress
      induced gastric mucosal damage The antisecretory properties of ebrotidine are
      similar to those of ranitidine and approximately 10-fold greater than those of
      cimetidine This drug exhibits anti-Helicobacter pylori activity that is
      synergistic with a number of antibacterial agents; it inhibits the urease enzyme
      and the proteolytic and mucolytic activities of H. pylori, and counteracts the
      inhibitory effects of H. pylori lipo-polysaccharide Ebrotidine is as effective as
      ranitidine for the treatment of patients with gastric or duodenal ulcers or
      erosive reflux oesophagitis Ebrotidine therapy results in significantly better
      ulcer healing rates than ranitidine treatment in patients who smoke.

PMID- 8736620
TI  - Gemfibrozil. A reappraisal of its pharmacological properties and place in the
      management of dyslipidaemia.
AB  - Gemfibrozil improves lipid and apolipoprotein profiles, particularly very low
      density lipoprotein (VLDL) triglyceride and high density lipoprotein (HDL)
      cholesterol levels, in patients with dyslipidaemia when administered at a total
      daily dose of 900 or 1200 mg. As demonstrated by the Helsinki Heart Study, these
      effects result in a reduction in some risk factors for coronary heart disease
      (CHD) and also a 34% reduction in the incidence of this disease after 5 years
      compared with placebo. Limited data suggest that gemfibrozil has beneficial
      effects on the fibrinolytic system and may slow the progression of
      atherosclerosis. Gemfibrozil has shown efficacy in the treatment of patients with
      type IIa, IIb, III, IV or V dyslipidaemia or hypoalphalipoproteinaemia,
      especially in patients with elevated triglyceride and low HDL cholesterol levels.
      It is also effective in patients with non-insulin-dependent diabetes mellitus
      (NIDDM) and dyslipidaemia and has no detrimental effects on glycaemic control. A
      small number of studies also showed gemfibrozil to be effective for the control
      of dyslipidaemia associated with renal failure, transplantation, nephrotic
      syndrome, arterial occlusive disease or systemic lupus erythematosus. However,
      patients with pre-existing CHD do not appear to derive the same benefits (reduced
      CHD mortality) from gemfibrozil therapy as these other patients, although results
      are based on studies of limited size and number. In general, gemfibrozil has at
      least similar efficacy to bile acid sequestrants and other fibric acid
      derivatives. Comparisons with HMG-CoA reductase inhibitors show these agents to
      produce different effects on lipid profiles from gemfibrozil. Thus, gemfibrozil
      would be expected to be superior in some patients (those with elevated
      triglyceride or VLDL cholesterol levels), but HMG-CoA reductase inhibitors should
      have greater benefits in those with elevated low density lipoprotein cholesterol
      levels. Thus, in patients with elevated triglyceride levels and low HDL
      cholesterol levels, and, particularly in patients with NIDDM, gemfibrozil is a
      useful treatment option, which has been shown to reduce the risk of CHD in middle
      aged men. However, limited available data prevents the accurate comparison of
      this agent with HMG-CoA reductase inhibitors in patients with this lipid profile.

PMID- 8736622
TI  - Docetaxel. A review of its pharmacodynamic and pharmacokinetic properties and
      therapeutic efficacy in the management of metastatic breast cancer.
AB  - Docetaxel is a member of the taxoid class of antineoplastic agents. Its mechanism
      of action is primarily related to its ability to enhance microtubule assembly and
      to stabilise microtubules by preventing their depolymerisation, thus disrupting
      normal cell division. Docetaxel has significant cytotoxic activity against human
      breast cancer cell lines and freshly explanted human breast cancer cells in
      vitro. It has also shown activity in mice against mammary tumours and human
      mammary tumour xenografts. Docetaxel has been investigated in the treatment of
      patients with advanced and/or metastatic breast cancer in European and North
      American phase II trials using an initial dose of 100 mg/m2 infused over 1 hour
      every 3 weeks. As first-line treatment, monotherapy with docetaxel was associated
      with complete and partial response rates of 5 to 16% and 49 to 53%, respectively,
      with an overall (complete plus partial) response rate of 54 to 68%. The median
      overall survival time of patients in one study was > or = 71 weeks. Docetaxel
      monotherapy has shown impressive activity as second-line therapy in patients with
      metastatic breast cancer who had relapsed while receiving adjuvant therapy or who
      had progressive disease following previous treatment, with overall response rates
      of 53 and 58% reported in 2 studies. A number of issues need to be addressed
      before the ultimate place of docetaxel in the management of metastatic breast
      cancer is fully established. The efficacy of docetaxel compared with standard
      agents and in combination regimens and its effect on quality-of-life aspects
      require further evaluation. Nevertheless, docetaxel is a promising new agent
      which has produced impressive clinical results and should be considered an
      alternative second-line treatment of patients with metastatic breast cancer.

PMID- 8736623
TI  - Diabetes mellitus in older patients. Is tight blood glucose control warranted?
AB  - Diabetes mellitus is a major health problem in the older population, where it is
      mainly of the non-insulin-dependent type [i.e. non-insulin-dependent diabetes
      mellitus (NIDDM)]. Epidemiological evidence and extrapolation of trial data from
      patients with insulin-dependent diabetes mellitus (IDDM) suggests that improving
      glycaemic control reduces the risk of developing microvascular complications
      (i.e. retinopathy, nephropathy and neuropathy) and also slows the rate of
      progression of these complications in patients with early disease. Macrovascular
      morbidity and mortality is, however, more common than microvascular disease in
      the older population and the evidence that improved glycaemic control
      significantly reduces the impact of macrovascular disease is weak. Thus, the
      overall benefits of tight glycaemic control are less well defined in older
      patients, who tend to have NIDDM, than in younger patients with IDDM. There are
      small but significant risks associated with tight glycaemic control in the older
      patient, including potentially fatal hypoglycaemia with sulphonyl-ureas and/or
      insulin, and fatal metformin-induced lactic acidosis. Patients at especially high
      risk of these complications can, however, be identified and inappropriate
      pharmacological intervention can be avoided.

PMID- 8736624
TI  - Treatment of post-stroke hypertension. A practical guide.
AB  - Cerebrovascular disease is a common cause of morbidity and mortality, especially
      in the elderly. Treatment of hypertension is effective in the primary prevention
      of stroke. Hypertension is seen in 80% of acute stroke patients but, by the tenth
      day after admission to hospital, only one-third are still hypertensive. The
      clinical significance of post-stroke hypertension is uncertain and its management
      is a contentious issue. In this article we review current evidence regarding the
      risks and benefits of the treatment of post-stroke hypertension. The
      pathophysiology of post-stroke hypertension is described in relation to
      autoregulation of cerebral blood flow after cerebral infarction or haemorrhage.
      In the absence of clinical trial data, recommendations for early treatment of
      post-stroke hypertension are based on a review of expert opinion that immediate,
      controlled lowering of blood pressure after acute stroke is required only in
      defined situations such as hypertensive encephalopathy or aortic dissection.
      There are no reliable data regarding the comparative effects of different
      hypotensive agents after acute stroke; short-acting vasodilator drugs are
      recommended if treatment is essential. The benefits of hypotensive therapy in
      secondary prevention of recurrent stroke are uncertain but the results of large
      clinical trials in progress should provide helpful guidelines for clinical
      practice.

PMID- 8736625
TI  - Diabetic neuropathy in elderly patients. What can be done?
AB  - The prevalence of diabetes mellitus increases markedly with age. Furthermore,
      advancing age is a strong risk factor for diabetic neuropathy, independent of the
      duration of diabetes mellitus and glycaemic control. Several biological changes
      occurring during the aging process may account for the facilitating effect of age
      on diabetic neuropathy. These include an increase in the production of advanced
      glycosylation end-products (AGEs), a defect in the polyol pathway, nerve vascular
      alterations and impaired resistance to oxidative stress. The clinical diagnosis
      of diabetic neuropathy is often difficult in elderly patients. The relationship
      between symptoms and neuropathy and that between neuropathy and diabetes mellitus
      are more difficult to ascertain in elderly patients due to age-related changes in
      the peripheral and autonomic nervous system and associated diseases frequently
      encountered in this population. Diagnosis of diabetic neuropathy is based on
      nerve conduction studies, vibratory perception threshold determination and
      assessment of autonomic function. For most of these tests, reference values are
      markedly influenced by age and their interpretation should use carefully age
      adjusted reference intervals. Identification of peripheral diabetic neuropathy
      indicates a high risk of foot complications, such as ulcers and gangrene, often
      resulting in amputation, whereas cardiovascular autonomic neuropathy is
      associated with an increased risk of postural hypotension and coronary events.
      All these risks increase markedly with aging. Therapeutic trials in elderly
      patients with diabetic neuropathy are lacking. Treatment of diabetic neuropathy
      consists of achievement of better glycaemic control and treatment of symptoms
      related to neuropathy. Specific treatments capable of preventing or curing
      neuropathy are under investigation. The interesting results obtained with aldose
      reductase inhibitors in animal studies contrast with disappointing results in
      patients with diabetes mellitus. Other metabolic approaches, like antioxidants
      and gamma-linolenic acid, seem promising. Clinical complications of diabetic
      neuropathy in the elderly are often severe. Early detection is required, since at
      the present time a preventive approach is the most effective way to avoid or
      postpone debilitating complications. More research is needed to make effective
      curative treatments of diabetic neuropathy available.

PMID- 8736626
TI  - Antidepressant-induced hyponatraemia in the aged. Avoidance and management
      strategies.
AB  - Antidepressant-induced hyponatraemia, while relatively uncommon, is an important
      clinical problem with serious consequences. Most antidepressants have been
      associated with hyponatraemia. Although the exact mechanism by which
      abnormalities of serum sodium level are produced is not known, most of the
      patients described in case reports meet the accepted criteria for the syndrome of
      inappropriate antidiuretic hormone secretion. Symptoms of hyponatraemia can mimic
      depression or psychosis, so awareness of this syndrome and periodic monitoring of
      serum electrolytes are important for early recognition. Stopping the medication
      and assuring normal extracellular fluid volume are the mainstay of treatment;
      rarely, intravenous infusion of hypertonic saline is required. After correcting
      the metabolic abnormalities, options for treatment of depression include:
      rechallenging with the same medication or initiating another antidepressant while
      carefully monitoring serum sodium level, or considering electroconvulsive
      therapy, if warranted by the clinical condition.

PMID- 8736621
TI  - Ciprofloxacin. An updated review of its pharmacology, therapeutic efficacy and
      tolerability.
AB  - Ciprofloxacin is a broad spectrum fluoroquinolone antibacterial agent. Since its
      introduction in the 1980s, most Gram-negative bacteria have remained highly
      susceptible to this agent in vitro; Gram-positive bacteria are generally
      susceptible or moderately susceptible. Ciprofloxacin attains therapeutic
      concentrations in most tissues and body fluids. The results of clinical trials
      with ciprofloxacin have confirmed its clinical efficacy and low potential for
      adverse effects. Ciprofloxacin is effective in the treatment of a wide variety of
      infections, particularly those caused by Gram-negative pathogens. These include
      complicated urinary tract infections, sexually transmitted diseases (gonorrhoea
      and chancroid), skin and bone infections, gastrointestinal infections caused by
      multiresistant organisms, lower respiratory tract infections (including those in
      patients with cystic fibrosis), febrile neutropenia (combined with an agent which
      possesses good activity against Gram-positive bacteria), intra-abdominal
      infections (combined with an antianaerobic agent) and malignant external otitis.
      Ciprofloxacin should not be considered a first-line empirical therapy for
      respiratory tract infections if penicillin-susceptible Streptococcus pneumoniae
      is the primary pathogen; however, it is an appropriate treatment option in
      patients with mixed infections (where S. pneumoniae may or may not be present) or
      in patients with predisposing factors for Gram-negative infections. Clinically
      important drug interactions involving ciprofloxacin are well documented and
      avoidable with conscientious prescribing. Recommended dosage adjustments in
      patients with impaired renal function vary between countries; major adjustments
      are not required until the estimated creatinine clearance is < 30 ml/min/1.73m2
      (or when the serum creatinine level is > or = 2 mg/dl). Ciprofloxacin is one of
      the few broad spectrum antibacterials available in both intravenous and oral
      formulations. In this respect, it offers the potential for cost savings with
      sequential intravenous and oral therapy in appropriately selected patients and
      may allow early discharge from hospital in some instances. In conclusion,
      ciprofloxacin has retained its excellent activity against most Gram-negative
      bacteria, and fulfilled its potential as an important antibacterial drug in the
      treatment of a wide range of infections. Rational prescribing will help to ensure
      the continued clinical usefulness of this valuable antimicrobial drug.

PMID- 8736627
TI  - Tuberculosis in the elderly. Epidemiology and optimal management.
AB  - The problem with the emergence of HIV-associated tuberculosis (which usually
      occurs in young adults) is that attention has been diverted away from the fact
      that, in the developed world, the elderly represent the biggest pool of
      tubercular disease and therefore the greatest pool of infection within the
      community. Although the incidence rate of tuberculosis continues to decline in
      most countries, there is evidence from parts of the developing world that rates
      may be beginning to increase. The presentation of the disease in the elderly is
      often uncharacteristic, e.g. disease tending to be more insidious in onset,
      pyrexia often absent and haemoptysis less common. Chest x-ray changes may also
      mislead the clinician in that disease is frequently present in the mid or lower
      zones. The elderly are probably at greater risk of extrapulmonary tuberculosis,
      which also presents in uncharacteristic ways. The diagnosis remains based on
      clinical presentation and the presence of smear and culture positivity, although
      some patients may be treated in the absence of microbiological proof. Standard
      treatment is with a combination of isoniazid, rifampicin and pyrazinamide, with
      or without a fourth drug such as ethambutol. The incidence of adverse effects in
      the elderly is much greater than that in younger patients, often resulting in the
      need to change the medication to drugs which are better tolerated. This may
      require changing to regimens which are less effective and therefore have to be
      taken for a longer period of time. The presence of concomitant disease such as
      liver or renal failure may also necessitate the administration of a suboptimal
      regimen. Mortality in elderly patients with tuberculosis is considerably higher
      than that in younger patients, even when treatment appears to have been started
      on time; even in the developed world mortality exceeds 30% in those patients over
      70 years of age.

PMID- 8736628
TI  - The value of influenza and pneumococcal vaccines in the elderly.
AB  - Influenza and pneumococcal vaccines have been available for decades and have
      repeatedly been shown to be efficacious in healthy adults. However, for both
      vaccines, efficacy in high risk populations and older individuals does not seem
      to be as great, leading to reluctance to use them as recommended. Recent
      observational studies in older individuals have confirmed and quantified the
      effectiveness of the 2 vaccines in situations of actual use. Economic data
      indicate that under realistic situations they are likely to reduce costs for
      healthcare systems. Societal benefits are now also established. While it may be
      useful to confirm the cost savings in additional systems of healthcare, the
      current emphasis should be to devise strategies to increase use of the vaccines.

PMID- 8736629
TI  - The role of nitric oxide in heart failure. Potential for pharmacological
      intervention.
AB  - There is now considerable evidence that nitric oxide (NO) production and action
      are abnormal in patients with heart failure. Spontaneous NO release from the
      vascular endothelium is preserved or enhanced in patients with heart failure and
      this may help to maintain tissue perfusion by blunting the vasoconstriction
      induced by various neurohumoral factors. On the other hand, endothelial NO
      release in response to various stimuli including exercise appears to be
      diminished and this may contribute to the impaired exercise capacity of patients
      with heart failure. It is now apparent that NO produced within the heart plays an
      important role in the modulation of cardiac contractility under physiological
      conditions. In patients with heart failure, however, increased myocardial NO
      production in response to cytokines such as tumour necrosis factor-alpha may
      contribute to reduced contractility and myocyte injury. Our understanding of the
      role of NO in the control of vascular tone has provided an explanation for the
      efficacy of nitrovasodilators in heart failure and has stimulated novel
      approaches to augmenting endogenous vascular NO production. There is also
      evidence that ACE inhibitors act to restore normal endothelial function in
      patients with heart failure. Increased NO production within the heart,
      particularly that produced via the pro-inflammatory inducible NO synthase, may be
      detrimental. It remains to be determined whether selective inhibition of
      inducible NO synthase can favourably modify the course of this lethal condition.

PMID- 8736631
TI  - Arachidonate transport through the blood-retina and blood-brain barrier of the
      rat during aging.
AB  - The permeability-surface area product (PS) of [I-14C]arachidonate at the blood
      retina (BRB) and blood-brain barrier (BBB) was determined after short carotid
      perfusion in Wistar rats at 4, 12 and 28 months of age. For the visual system
      structures, parietal and frontal cortex, striatum, hypothalamus, hippocampus and
      olfactory bulb there was no significant difference among mean PSs in any age
      group. Our results indicate that: (1) arachidonate is able to cross at relevant
      rate BRB and BBB; (2) in all brain regions except retina, optic tract and
      hippocampus, blood barriers have a transport capacity for arachidonate
      significantly higher than that for docosahexaenoate and palmitate as well; (3)
      aging does not affect influx into retina and other structures of rat central
      nervous system of the arachidonate, a metabolic substrate rapidly incorporated
      into microcapillary and brain lipids, and for which simple diffusion transport
      across the BRB and BBB may be postulated.

PMID- 8736630
TI  - Amitriptyline. A review of its pharmacological properties and therapeutic use in
      chronic pain states.
AB  - Amitriptyline is a tricyclic antidepressant agent which also has analgesic
      properties. Whether its analgesic effects are linked to its mood-altering
      activity or attributable to a discrete pharmacological action (or a combination
      of both) is unknown. Clinical trials demonstrate that oral amitriptyline achieves
      at least a good or moderate response in up to two-thirds of patients with post
      herpetic neuralgia and three-quarters of patients with painful diabetic
      neuropathy, neurogenic pain syndromes that are often unresponsive to narcotic
      analgesics. Amitriptyline has also demonstrated efficacy in heterogeneous groups
      of patients with chronic non-malignant pain. Other possible areas of use for
      amitriptyline are in patients with fibromyalgia or as an adjuvant for
      uncontrolled cancer pain, although evidence for the latter application is
      limited. Adverse events resulting from the antimuscarinic activity of
      amitriptyline (primarily dry mouth and sedation) are commonly reported, even at
      the low dosages used for the control of pain. Low starting doses and careful
      dosage titration may help to minimise these effects. Orthostatic hypotension and
      tachycardia, sometimes associated with tricyclic antidepressant agents, may also
      pose a problem in the elderly. In summary, amitriptyline has a valuable place in
      the treatment of chronic pain conditions that affect the elderly provided that
      the drug is used judiciously to minimise adverse effects. Importantly,
      amitriptyline remains the best studied of the antidepressant agents in post
      herpetic neuralgia and diabetic neuropathy and is an important and effective
      treatment option in these syndromes.

PMID- 8736632
TI  - Developing brain cells produce factors capable of inducing the HT7 antigen, a
      blood-brain barrier-specific molecule, in chick endothelial cells.
AB  - Homeostasis of the neural microenvironment is maintained by the blood-brain
      barrier (BBB). To analyze the molecular mechanisms by which the BBB is induced
      during embryonic development, we have taken advantage of an in vivo model of BBB
      induction based on the expression of the HT7 cell surface protein. This protein
      is a transmembrane glycoprotein of the immunoglobulin superfamily. It is
      expressed in the chick BBB-forming endothelial cells, but not in peripheral
      endothelial cells. Here we show that the HT7 protein is induced in vessels which
      had vascularized a quail embryonic brain graft transplanted in the coelomic
      cavity of chick embryo. The quail brain graft was vascularized by both chick and
      quail-derived vessels. All chick host-derived vessels in the brain transplant
      were found to express HT7 while the neighboring chick vessels were negative. We
      conclude that the invading host endothelial cells differentiated into BBB-forming
      vessels under the influence of developing quail brain cells. This model
      reproduces the BBB induction during development. It may be useful for further
      approaches to study the molecular mechanisms involved in BBB induction.

PMID- 8736633
TI  - Effects of phencyclidine metabolites on serotonin uptake in rat brain.
AB  - The effects of phencyclidine (PCP) and its metabolites on serotonin (5
      hydroxytryptamine, 5-HT) receptors were studied. PCP and its metabolites
      inhibited the uptake of [3H]5-HT and the binding of [3H]paroxetine in rat brain,
      while they failed to inhibit either [3H]5-HT binding to 5-HT1 receptors or
      [3H]ketanserin binding to 5-HT2 receptors. The trans-isomer of 4-phenyl-4-(I
      piperidinyl)cyclo-hexanol (trans-4-PPC), the major metabolite of PCP, rather than
      PCP itself, inhibited [3H]5-HT uptake most potently. These results suggest that
      the serotonergic effects of PCP, in part, may be based on the effects of PCP
      metabolites on 5-HT uptake.

PMID- 8736634
TI  - Embryonic genes expressed in Alzheimer's disease brains.
AB  - Alzheimer's disease (AD)-specific or characteristic gene expression was explored
      by the identification of cDNA clones by means of differential screening for
      embryonic brain cDNA library with 32P-labeled cDNA probes prepared from mRNA of
      AD and normal human brains. To isolate neuronal genes in degenerating neurons, we
      used rat embryonic cDNA library at stage day 15 when glial cells developed poorly
      in the brain. Seventeen embryonic genes were identified as embryonic alpha
      tubulin, embryonic beta-tubulin, hnRNP, protein L-isoaspartyl methyltransferase
      (PIMT), ferritin heavy chain, type IV collagen, actin-binding protein cofilin,
      profilin and nine novel sequences designated as A1-9. We characterized these
      genes by Northern blot analysis, RNase protection assay and immunohistochemical
      studies, showing that PIMT and a novel gene designated as A5 showed the
      transcriptional up-regulation in AD brains. In addition, the immunohistochemical
      studies showed PIMT, type IV collagen, and cofilin were associated with
      neurofibrillary tangles in degenerating neurons, brain vessels in affected
      regions, and synaptosomal structures in AD brains, respectively. The catalogue
      presented here also showed the involvement of cytoskeletal proteins, cytoskeleton
      associated proteins, and an iron-storage protein, suggesting the presence of
      regenerating activity and the abnormal metabolisms in affected neurons of AD
      brains.

PMID- 8736635
TI  - Reduction in number of dopamine uptake sites but unchanged number of piperazine
      acceptor/CYP450IID6 binding sites in the human caudate nucleus in aging.
AB  - A substantial decrease in number of striatal dopamine uptake sites is a
      characteristic finding in aging. This decrease resembles the dopaminergic nigro
      striatal degeneration in Parkinson's disease (PD). A dysfunction of cytochrome
      P450IID6 (debrisoquine-4-hydroxylase) is suggested to be involved in the
      pathogenesis of PD. In this study, binding sites associated with the neuronal
      form of P450IID6 were studied in the caudate nucleus from individuals in the age
      range 20-81 years using [3H]GBR 12935 as a radioligand. No significant changes in
      binding parameters were obtained, while in the same region a significant decrease
      in number of dopamine uptake sites occurred. Thus, in aging, P450IID6 and
      dopaminergic degeneration seem not to be functionally related in this region.
      Whether such a relation exists in PD is still to be examined.

PMID- 8736636
TI  - Local administration of morphine decreases the extracellular level of GABA in the
      periaqueductal gray matter of freely moving rats.
AB  - Opioids are generally believed to activate descending pain inhibitory pathways
      from the periaqueductal gray matter (PAG). Since opioids exert an inhibitory
      effect on neural excitability and transmitter release, an opioid-mediated
      inhibition of tonically active inhibitory gamma-aminobutyric acid (GABA) neurons
      has been suggested to mediate this effect. The aim of the present microdialysis
      study was to investigate the effect of local administration of morphine on the
      extracellular GABA level in the PAG of awake rats. The recently developed and
      highly sensitive method of capillary electrophoresis with laser-induced
      fluorescence detection was used for GABA determination in microdialysate samples
      obtained from the PAG of freely moving rats. The basal GABA level was 54.5 +/-
      6.6 nM (n = 8; mean +/- SEM). Perfusion of the dialysis probe with morphine (100
      microM) for 30 min significantly decreased the GABA level to 28.2 +/- 4.2 nM (n =
      8; P < 0.05). The effect of morphine was reversed by coperfusion with naloxone
      (100 microM in the perfusion fluid). The present results thus provide direct
      experimental evidence for an opioid-induced inhibition of tonic GABA release in
      the PAG, which may in turn lead to a disinhibition of descending pain inhibitory
      pathways.

PMID- 8736637
TI  - Structural and functional analogs of CuZn superoxide dismutase inhibit rat brain
      nitric oxide synthase by interference with the reductase (diaphorase) domain.
AB  - Copper complexes with superoxide dismutase (SOD) activity show a wide range of
      pharmacological activities. We have investigated the effect of ([N,N'-bis(2
      pyridylmethylene)-1,4-butanediamine]-(N,N',N", N"')]-Cu(II)-chloride (Cu-PuPy)
      and ([N,N'-bis(2-pyridyl-phenyl)methylene-1,4-butanediamine]-(N,N',N", N"'))
      Cu(II)-chloride (Cu-PuPhePy) on the multiple catalytic functions of rat brain NO
      synthase (NOS). Both drugs inhibited the formation of L-citrulline as well as the
      enzymatic reduction of cytochrome c. The uncoupled oxidation of NADPH, catalyzed
      by neuronal NOS in the absence of L-arginine, was inhibited by Cu-PuPy but
      stimulated by Cu-PuPhePy, suggesting that the phenyl-substituted compound acts as
      a parasitic electron acceptor. Our data identify copper complexes with SOD
      mimicking activity as a novel class of neuronal NOS inhibitors blocking the
      reductase (diaphorase) activity of the enzyme.

PMID- 8736638
TI  - Temporal and spatial appearance of the membrane cytoskeleton and perineuronal
      nets in the rat neocortex.
AB  - Parvalbumin-immunoreactive interneurons are surrounded by perineuronal nets,
      containing molecules of the extracellular matrix (e.g. tenascin-R). Furthermore,
      they seem to have a special cytoskeleton composed of, among others, ankyrinR and
      beta Rspectrin. In the present developmental study we showed that the
      intracellular markers parvalbumin, ankyrinR and beta Rspectrin as well as Vicia
      Villosa agglutinin, an extracellular marker for perineuronal nets, appeared in
      the second postnatal week. In the third postnatal week, ankyrinR and beta R
      spectrin were present in the parvalbumin-positive interneurons. Tenascin-R
      appeared in a similar topographic distribution as the intracellular markers. The
      adult pattern was established upon the end of the fourth postnatal week. Our
      results indicate that cytoskeletal maturity maybe a prerequisite for the
      organization of perineuronal nets of extracellular matrix.

PMID- 8736639
TI  - Organotypic cortex-striatum-mesencephalon cultures: the nigrostriatal pathway.
AB  - We were successful in developing cortex-striatum-mesencephalon organotypic
      cultures from the rat brain after 4-9 weeks in vitro. A modification of the
      'roller tube' technique was employed where slices were embedded in a
      plasma/thrombin clot onto a Millicell membrane on a coverslip. The underlying
      membrane provided high mechanical stability during culturing, which reduced the
      likelihood of deterioration of the cultures. Tyrosine hydroxylase
      immunoreactivity was used to label dopamine neurons and axonal innervation into
      the cortical and striatal culture. The electrophysiological responses of striatal
      medium-sized spiny neurons to cortical, striatal and mesencephalic stimulation
      were characterized.

PMID- 8736640
TI  - In vivo regulation of acetylcholine release via adenosine A1 receptor in rat
      cerebral cortex.
AB  - The roles of the endogenous adenosine on acetylcholine release via adenosine A1
      receptor were investigated in rat cerebral cortex using brain microdialysis. Oral
      administration of KF15372 (8-dicyclopropylmethyl-1,3-dipropylxanthine), a novel
      selective adenosine A1 receptor antagonist, at doses of 1.25, 5, and 20 mg/kg,
      significantly increased the extracellular levels of acetylcholine in rat cerebral
      cortex. Selective A1 agonist N6-((R)-phenylisopropyl) adenosine (R-PIA) did not
      affect the extracellular level of acetylcholine by both oral (1.25 mg/kg) and
      intracortical administrations (0.3 microM) via dialysis probe. These results
      suggest that the extracellular level of acetylcholine is under tonic inhibitory
      control of endogenous adenosine via the A1 receptor.

PMID- 8736641
TI  - Regional activation of human cerebral cortex upon an adaptation in mirror
      drawing.
AB  - To elucidate cerebral regions involved in adaptation to mirror drawing, changes
      in regional cerebral blood flow were measured using positron emission tomography
      at different levels of adaptation. A significant signal in subtraction images was
      localized in left Brodmann's area 45 (ventral sub-region of Broca's area) in the
      initial phase of the mirror drawing. This activity decreased as adaptation
      proceeded, and a small cluster in area 19 of the medial extrastriate cortex
      became significantly active. An after-effect of ca. 30 min of mirror-drawing was
      also detected in the right area 21 of the temporal association cortex. The
      results first demonstrated visuo-cortical regions where neurons might change
      their activity to evoke plastic response to the inverted vision.

PMID- 8736642
TI  - Modulation of phosphoinositide turnover by chronic nicergoline in rat brain.
AB  - Basal and agonist-stimulated phosphoinositide (PI) turnover and inositol 1,4,5 
      trisphospate (InsP3) content in rat brain were investigated after chronic
      nicergoline (SERMION) treatment. Oral administration of nicergoline (5 mg/kg
      b.i.d. for 7 weeks) enhanced the basal turnover of PI in the cerebral cortex
      compared to controls. This effect was paralleled by a significant rise of
      cortical InsP3 levels. No significant changes of noradrenaline- or carbachol
      induced accumulation of [3H]-inositol-I-phophate ([3H]-InsP1) were found in
      cortices from nicergoline-treated rats. On the contrary, in the striatum
      nicergoline significantly potentiated the responsiveness of noradrenaline- and
      carbachol-stimulated PI turnover, leaving unchanged the basal production of [3H]
      InsP1 and InsP3 levels. The results suggest that the interaction of nicergoline
      with PI transducing pathway might have relevance to the mechanisms of action of
      nicergoline.

PMID- 8736643
TI  - Manganese and 1-methyl-4-(2'-ethylpheny1)-1,2,3,6-tetrahydropyridine induce
      apoptosis in PC12 cells.
AB  - Oxidative stress is thought to play a key role both in the neurotoxin MPTP- and
      manganese (Mn)-induced neurotoxicity and in apoptotic cell death. In the present
      study, we report that Mn and the MPTP analogue 1-methyl-4-(2'-ethylphenyl)
      1,2,3,6-tetrahydropyridine (2'Et-MPTP), which is metabolized by MAO-A to 1-methyl
      4-(2'-ethylphenyl)-pyridinium ion (at concentrations of 0.5 and 1.0 mM), induced
      apoptosis in PC12 cells. Apoptosis was tested by terminal deoxynucleotidyl
      transferase-mediated 2'-deoxy-uridine-5'-triphosphate nick end labelling (TUNEL)
      technique, flow cytometry and fluorescence microscopy. Both Mn and 2'Et-MPTP
      induced also a time-dependent decrease in cell viability, as determined by the 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Only Mn
      induced apoptosis and decrease in cell viability were inhibited by the
      antioxidant ascorbic acid. We conclude that apoptosis may be an important
      mechanism of cell death in MPTP- and Mn-induced parkinsonism. However, an
      oxidative stress mechanism may be recognized only in the Mn-induced apoptosis.

PMID- 8736644
TI  - High-speed voltage-sensitive dye imaging of an in vivo insect brain.
AB  - We have developed an improved optical recording technique with high spatio
      temporal resolution to investigate neural activity from an in vivo insect brain.
      Optical images were acquired from hawk moth antennal lobe (AL) neurons. When
      activity was elicited by electrical stimulation of the antennal nerve using a
      stereoscopic microscope, depolarization followed by hyperpolarization was
      consistently recorded in the AL. When gamma-aminobutyric acid (GABA)-mediated
      synaptic transmission was blocked by the picrotoxin, the typical
      hyperpolarization was greatly reduced while no changes were observed in the
      depolarization. This suggests that the hyperpolarization results from inhibitory
      postsynaptic potentials (IPSPs) originating from GABA-sensitive chloride channels
      on the AL neurons.

PMID- 8736645
TI  - Effect of conditioned fear stress on dopamine release in the rat prefrontal
      cortex.
AB  - The effects of conditioned fear stress (CFS) on dopamine release in the medial
      prefrontal cortex were studied by in vivo microdialysis in the rat. CFS (exposure
      to an environment in which foot-shock had been delivered previously) induced a
      marked suppression of motility, i.e., freezing behavior. Extracellular
      concentrations of dopamine in the medial prefrontal cortex were increased by CFS.
      The increase of dopamine returned to the pretreatment levels when rats were
      returned to the home cages. Diazepam (0.5 mg/kg, i.p.) suppressed both the CFS
      induced freezing behavior and extracellular dopamine levels in the medial
      prefrontal cortex. These findings suggest that anxiety and dopamine release in
      the prefrontal cortex might be related.

PMID- 8736646
TI  - Correlated discharges of two neurons in rat gustatory cortex during gustatory
      stimulation.
AB  - During application of tastants into the oral cavity correlated activities were
      observed in 27 of 64 neuron pairs recorded simultaneously in the gustatory cortex
      of anesthetized rats. The mean frequency of correlated discharges as assessed
      from the size of the peak appearing in the cross-correlogram was lower (0.2-0.33
      spikes/s) and the mean width of the peaks was wider (8 ms) as compared to those
      reported in the gustatory relay stations in the brainstem. In a few cases troughs
      were formed or peaks appeared with a long delay.

PMID- 8736647
TI  - Glucose-induced decrease in glutamate levels in ischemic human brain by in-vivo
      microdialysis.
AB  - Glutamate is one of the principal neurotoxins in the pathogenesis of ischemic
      neuronal injury. Elevated glutamate levels in ischemia have been well documented
      in many animal stroke models. Recent work in humans also shows a similar trend.
      We have used our acute focal ischemic model of the human brain to study the
      response of glutamate levels by in vivo microdialysis during ischemia using two
      different perfusates. The addition of 30 mM of glucose to the perfusate
      attenuated the percentages of dialysate glutamate levels from 4.27 +/- 1.7 to
      1.34 +/- 0.47 (P < 0.001) during partial ischemia and from 21.42 +/- 6.05 to 7.25
      +/- 1.43 (P < 0.05) with total ischemia. The pre-ischemic values of glutamate
      were similar with the two perfusates. These results indicate that the ischemia
      induced rise in glutamate is attenuated by exogenous glucose delivery in the
      human stroke model.

PMID- 8736648
TI  - 5-HT1D-like receptors inhibit the release of endogenously formed [3H]GABA in
      human, but not in rabbit, neocortex.
AB  - Both human and rabbit brain contain the 5-hydroxytryptamine (5-HT)1D subtype of 5
      HT1 receptors. We studied the effects of 5-HT1D receptor stimulation on
      neocortical [3H] gamma-aminobutyric acid (GABA) release from GABAergic neurons in
      these species. The 5-HT1D receptor agonist sumatriptan depressed [3H]GABA release
      in human neocortex and the 5-HT1 receptor antagonist metitepin prevented this
      depression with potencies suggesting mediation by 5-HT1D-like receptors. In
      rabbit neocortex, however, 5-HT1D agonists did not affect the release of
      [3H]GABA. Since 5-HT and GABA seem to function antagonistically in anxiety
      disorders their neocortical interaction may be (patho)physiologically relevant.

PMID- 8736649
TI  - Functional modulation of the human flexion and crossed extension reflexes by body
      position.
AB  - The effects of body position on the electrically evoked flexion (FR) and crossed
      extension reflexes (CER) were investigated in humans. The FR area in the
      ipsilateral tibialis anterior muscle was significantly smaller during sitting
      than supported stance by 36% (P < 0.01). In contrast, the excitability of
      extensor muscles on both sides was enhanced in standing. For instance, twice as
      many subjects manifested a response in the ipsilateral vastus lateralis (VL) and
      the contralateral VL and/or soleus muscles (i.e. the CER) in standing than
      sitting. The FR and CER modulation observed seems to be dictated by the
      difference in functional demand between sitting and supported stance.

PMID- 8736650
TI  - Asthma and chronic bronchitis: similarities and differences.

PMID- 8736651
TI  - Methods to improve the diagnostic accuracy of malignant mesothelioma.

PMID- 8736652
TI  - HLA antigens and asthma in Greeks.
AB  - HLA-A and -B antigens were determined in a group of 76 Greek asthmatic patients:
      35 children (1.5-15 years) and 41 adults (18-73 years). The results were compared
      to those of 400 healthy unrelated controls from the same population. The standard
      NIH lymphocytotoxicity test was applied. When all 76 patients were compared to
      the controls, a statistically significant lower frequency of HLA-B5 and -B35
      antigens was noted. When adults were analysed alone, an increased frequency of
      HLA-B8 was found. On the other hand, in the asthmatic children sub-group, the HLA
      A10 antigen was significantly higher and the HLA-B5 was significantly lower than
      in the controls. These data imply that different HLA antigens may be involved in
      the pathogenesis of several clinical forms of asthma and that, in order to study
      the role of immunogenetic factor(s) in the pathogenesis of this disease, more
      adequate grouping criteria are needed.

PMID- 8736653
TI  - A comparison of the clinical efficacy and patient acceptability of terbutaline
      Turbuhaler and salbutamol Rotahaler, in adult patients with asthma.
AB  - This open randomized, cross-over study compared the clinical efficacy and patient
      acceptability of the two bronchodilator delivery systems, terbutaline Turbuhaler
      (0.5 mg t.i.d.) and salbutamol Rotahaler (0.4 mg t.i.d.), each given for 3 weeks.
      Thirty-two adult asthmatics (21 males and 11 females with a mean age of 34 years)
      who demonstrated at least 15% reversibility in PEF or FEV1 in response to
      terbutaline, were enrolled for study. The median reversibility in FEV1 was 27.5%
      for the terbutaline-salbutamol group and 21% for the salbutamol-turbutaline
      group. Two patients discontinued during terbutaline treatment (one due to
      respiratory infection and one due to tachycardia, exhaustion and tremor) and five
      patients were lost to follow-up during salbutamol treatment, leaving data from 25
      patients for an 'all patients treated' analysis. Mean morning PEF was 426 l min-1
      during terbutaline and 410 l min-1 during salbutamol (difference 16 l min-1, 95%
      CI of difference 3-28 l min-1, P = 0.016), and mean evening PEF was 446 l min-1
      during terbutaline and 428 l min-1 during salbutamol (difference 18 l min-1, 95%
      CI 5-30 l min-1, P = 0.0076). No significant differences were detected in diary
      symptom scores or in use of additional study drug during the day or night, and no
      serious adverse events were reported. When asked to state their treatment
      preferences on the basis of effects, side-effects and overall, more patients
      preferred Turbuhaler in each case, although no statistically significant
      differences were detected. In conclusion, terbutaline via Turbuhaler was
      significantly more effective than salbutamol via Rotahaler in controlling lung
      function (mean daily PEF) in adults with mild to moderate asthma, and it was the
      preferred treatment overall in 44% of patients, compared with 16% for Rotahaler
      (n.s.).

PMID- 8736654
TI  - Study of paradoxical response to chemotherapy in tuberculous pleural effusion.
AB  - BACKGROUND: Paradoxical worsening of disease, in spite of effective chemotherapy
      for tuberculosis, has been reported to occur in cases of intracranial
      tuberculoma, lymph node, and pulmonary tuberculosis. However, only rare case
      reports describe such paradoxical response in tuberculosis pleurisy. METHODS:
      Sixty-one patients with proven tuberculous pleural effusion were retrospectively
      screened in Riyadh, Saudi Arabia, in three major hospitals to look systematically
      at the incidence and features of paradoxical response. RESULTS: Paradoxical
      increase in the size of the effusion was detected in 10 of 61 patients. In six
      patients, the effusion became massive with worsening of dyspnoea requiring the
      use of corticosteroids in five patients and therapeutic aspiration in all six.
      However, complete resolution occurred in all 10 patients within 1-3 months. Three
      out of the 10 patients developed residual pleural thickening. CONCLUSION: An
      incidence of 16% (10/61) paradoxical worsening of tuberculous effusion following
      the start of anti-tuberculous treatment has been documented. This resulted in
      respiratory distress necessitating therapeutic re-aspiration in six of 10
      patients.

PMID- 8736655
TI  - IL-8 in pleural effusion.
AB  - Interleukin-8 (IL-8) is a recently described potent chemotactic factor that may
      be involved in the pathogenesis of pleural effusions. To understand the actual
      mechanisms mediating the inflammatory response, changes in cellular components
      and IL-8 level in pleural fluid of different aetiologies were evaluated. Thirty
      four patients (19 male, 15 female) with a mean age of 46 +/- 22 years (range 16
      92) were included in the study. Of these, 13 had tuberculous pleural effusion,
      seven had empyema/parapneumonic pleural effusion, and 14 had malignant pleural
      effusion (seven adenocarcinoma, three ovarian carcinoma, two lymphoma, one
      chronic myeloid leukaemia, and one small cell carcinoma) with positive cytology.
      Differential cell counts in the pleural fluid were obtained using cytocentrifuge
      preparations. The concentrations of IL-8 in pleural fluid were measured by the
      ELISA method. Interleukin-8 was detected in all 34 pleural fluid samples. The
      serum IL-8 level was analysed only in the empyema/parapneumonic pleural effusion
      group. The mean IL-8 levels of tuberculous, empyema/parapneumonic, and malignant
      pleural effusions were 1420 +/- 1049 pg ml-1, 4737 +/- 2297 pg ml-1, and 1574 +/-
      1079 pg ml-1, respectively. The IL-8 levels in the empyema/parapneumonic group
      were significantly raised over malignant and tuberculous groups (P < 0.02). The
      mean pleural fluid neutrophil counts in tuberculous, empyema/parapneumonic and
      malignant pleural effusions were 315 +/- 575 cells mm-3, 11,136 +/- 12,452 cells
      mm-3, and 635 +/- 847 cells mm-3, respectively (P < 0.003). There was a
      significant positive correlation between pleural IL-8 levels and neutrophil
      counts (r = 0.46, P < 0.006). The levels of IL-8 in paired samples of serum and
      pleural fluid in the empyema/parapneumonic effusion group were compared, and the
      concentration of IL-8 was higher in the pleural effusion than serum (means, 4737
      +/- 2297 pg ml-1 and 130.0 +/- 62.5 pg ml-1, respectively, P < 0.03). There was a
      significant negative correlation between IL-8 concentrations in serum and pleural
      fluid (r = -0.80, P < 0.03). This data suggests that production of IL-8 in
      pleural effusion may play a key role in initiation and maintenance of
      inflammatory reactions, especially in empyema/parapneumonic pleural effusions. It
      may offer the basis for introduction of novel anti-inflammatory agents in
      treatment.

PMID- 8736656
TI  - Lung involvement in systemic sclerosis (scleroderma): relation to classification
      based on extent of skin involvement or autoantibody status.
AB  - Lung involvement accounts for significant morbidity and is a leading cause of
      mortality in patients with systemic sclerosis (SSc). It has been shown that
      different patterns of pulmonary involvement are seen in different subtypes of
      SSc. This paper reports a retrospective review of 72 patients with SSc to
      determine whether disease classification according to the extent of skin
      involvement alone (diffuse vs. limited) or autoantibody status was predictive of
      pulmonary parenchymal involvement. The diagnosis of interstitial lung disease was
      based on pulmonary function tests and chest radiographs. Restrictive lung disease
      was common in both limited SSc (lSSc) and diffuse SSc (dSSc), occurring in 30%
      and 50% of these patients respectively (P = 0.16). Radiographic evidence of
      significant interstitial disease was also comparable between the groups [nine of
      32 lSSc patients (28%) vs. six of 17 dSSc patients (32%), P = n.s.]. No
      significant difference in mean lung function was found between patients with anti
      Scl 70 antibody (n = 12) compared to those without (n = 60) (TLC 79.0 +/- SE 5.1%
      predicted vs. 82.8 +/- 2.2, P = n.s.; DLCO 63.0 +/- 5.1 vs. 59.7 +/- 2.5, P =
      n.s.). By contrast, statistically significant differences in mean lung function
      were found between patients with anticentromere antibody (ACA) (n = 24) and those
      without ACA (n = 48) (TLC 98.6 +/- SE 3.9% predicted vs. 79.7 +/- 3.1%, P <
      0.001); and less frequent radiographic evidence of severe interstitial disease (0
      of 17 with significant interstitial changes on chest radiograph vs. 15 of 32
      (47%), P = 0.002). It is concluded that classification of SSc patients on the
      basis of the distribution of skin involvement poorly predicts the occurrence of
      interstitial lung disease. On the other hand, ACA is highly associated with the
      absence of interstitial lung disease.

PMID- 8736657
TI  - Maximum inspiratory and expiratory pressures have no daytime variation in healthy
      men.
AB  - The variation of maximal respiratory pressures (Pimax and Pemax) in healthy
      subjects were studied on the same day in 16 non-smoking healthy men (age 26.2 +/-
      3.2 years). The Pimax and Pemax were obtained on three occasions (8 a.m., 2 p.m.
      and 9 p.m.) within the same day. There were no differences between readings for
      Pimax and Pemax values.

PMID- 8736658
TI  - Re-expansion pulmonary oedema following spontaneous pneumothorax.
AB  - Re-expansion pulmonary oedema may occur after chest tube drainage of pneumothorax
      and can give rise to cardiopulmonary manifestations which range from the mild to
      the severe. In order to evaluate the prevalence and the clinical manifestations
      of this complication, all patients with spontaneous pneumothorax managed with
      chest tube drainage were evaluated over an 8-yr period (1986-1994). A chest
      radiograph was performed routinely in all patients within 4 h of tube insertion.
      Lung expansion and the appearance of infiltrates within the lungs were
      investigated specifically. Re-expansion oedema was noted in three of 320 episodes
      (0.9%). Two of the three patients needed rapid and extensive clinical treatment.

PMID- 8736659
TI  - Acute massive pulmonary haemorrhage, pulmonary embolism and deep vein thrombosis
      in a patient with systemic lupus erythematosus and varicella.

PMID- 8736660
TI  - Menthol and aspirin-induced asthma.

PMID- 8736661
TI  - Raised brain natriuretic peptide in pulmonary hypertension.

PMID- 8736662
TI  - Bronchiectasis and Felty's syndrome.

PMID- 8736663
TI  - A matter of law?

PMID- 8736664
TI  - Common law correction.

PMID- 8736665
TI  - After the fact.

PMID- 8736666
TI  - Institutional review boards. A net too thin.

PMID- 8736667
TI  - At the juncture of theory and practice. Remarks on receiving the Henry Knowles
      Beecher Award.

PMID- 8736668
TI  - Ethics as design. Doing justice to moral problems.

PMID- 8736670
TI  - Society's diseases.

PMID- 8736671
TI  - Liberty, equality, death!

PMID- 8736672
TI  - Judging the past. The case of the human radiation experiments.

PMID- 8736673
TI  - Judging the other. Responding to traditional female genital surgeries.

PMID- 8736674
TI  - Cross-cultural miscommunication.

PMID- 8736675
TI  - The significance of glucose turnover in the brain in the pathogenetic mechanisms
      of Alzheimer's disease.
AB  - This paper presents a comprehensive survey of the pathogenesis and
      pathophysiology of Alzheimer's disease (AD). Two mechanisms are of etiological
      importance in the development of a degenerative dementing brain disease: 1.
      Lesions in the mitochondrial genome that are caused by free radicals. Primary
      degenerative AD is characterized by a tendency to acquire random lesions within
      mitochondrial DNA that are produced by free radicals. The consequence of these
      lesions is a decrease in glucose turnover and a decline in oxidative
      phosphorylation. Point mutations on chromosome 21 are hypothesized to increase
      the susceptibility of mitochondrial DNA to lesions created by free radicals. 2.
      Ischemic brain lesions as well as traumatic brain damage cause an increase in the
      release of excitotoxic amino acids (glutamate, aspartate, etc.). These
      neurotransmitters increase CA(+2) influx into the nerve cell and significantly
      lower energy production. From a pathogenetic point of view, AD is characterized
      by a decrease in glucose turnover in the brain. The progression of AD can be
      monitored by F18- deoxyglucose PET studies. This technique also allows the
      recognition of patients who are prone to develop AD. The actual development of a
      cognitive deficit is a threshold phenomenon that occurs if glucose turnover in
      the hippocampus or temporoparietal cortex drops below a critical level of about
      40% of the level of age-matched controls. The low glucose turnover in AD causes a
      cholinergic deficit by decreasing the synthesis of AcCoA, which is used by
      choline acetyltransferase in the acetylation of choline to acetylcholine. The
      decrease in glucose turnover also reduces oxidative phosphorylation. The
      resulting decrease in ATP triggers the hyperphosphorylation of tau protein by
      activating protein kinase 40erk. The hyperphosphorylation leads to the
      development of paired helical filaments. The generation of beta amyloid and the
      loss of neuronal synapses are also caused by a decrease in oxidative
      phosphorylation, since beta amyloid precursor proteins are not inserted into the
      membranes of nerve cells in the absence of a sufficient amount of ATP. This
      results in the generation of intact beta amyloid molecules and leads to
      amyloidosis in the brains of patients with Alzheimer's disease.

PMID- 8736676
TI  - Protein folding, nucleation phenomena and delayed neurodegeneration in
      Alzheimer's disease.
AB  - This hypothesis attempts to explain how Alzheimer's disease can be both sporadic
      and autosomal dominant with catastrophic neurodegeneration occurring after
      decades of normal function. The production of A beta peptide, the subunit of
      amyloid plaques, from the ubiquitous amyloid precursor protein is discussed.
      Conformational changes are argued to be crucial to the formation of these amyloid
      plaques and to their neurotoxicity. Parallels are drawn with prion disease where
      similarly a normal cellular protein becomes pathogenic once a conformational
      change is induced. Post-mitotic neurons in the brain are susceptible to this
      destructive process which is initiated by nucleation phenomena and is then self
      propagating. An understanding of the conformational changes involved in plaque
      formation may open new therapeutic avenues in Alzheimer's disease.

PMID- 8736677
TI  - Associative synaptic plasticity in hippocampus and visual cortex: cellular
      mechanisms and functional implications.
AB  - Synchronous pre- and postsynaptic neuronal activity results in long-term
      potentiation (LTP) of excitatory synaptic transmission in the hippocampus and the
      neocortex. Induction of this form of potentiation requires calcium influx
      mediated by NMDA receptors. Experimental evidence is reviewed for induction of
      long-term depression (LTD) of synaptic transmission in the hippocampus in vitro
      and neocortical neurons in vivo, when the discharge of the postsynaptic neuron is
      temporally decorrelated from the presynaptic stimulation. Homosynaptic LTD
      induced by low frequency tetani in the hippocampus in vitro requires NMDA
      receptor activation and a moderate calcium influx. The role of postsynaptic
      calcium as a key parameter in the encoding of temporal contiguity of neural
      activity and its possible implications in the formation of engrams during
      specific learning tasks are discussed.

PMID- 8736678
TI  - The role of conduits in nerve repair: a review.
AB  - The restoration of effective and meaningful axonal function following peripheral
      nerve injury continues to be a considerable clinical challenge. The use of
      conduits to bridge the gap between severed ends is a contemporary experimental
      maneuver that isolates the microenvironment of regenerating axons. Entubulation
      has allowed analysis and manipulation of putative influences upon nerve
      regeneration. A review is provided of the research efforts that have explored the
      neurobiological and mechanical factors that guide nerve regeneration within
      conduits. Levels of specificity, from tissue specific growth to end-organ
      specific growth, are outlined within the framework of the theories of
      Neurotropism, Contact Guidance and Neurotrophism. Included are investigations
      utilizing different conduit materials and the few clinical applications of these
      conduits. A number of chamber manipulations, extra-cellular matrix substrates and
      growth factors and their molecular receptors have been implicated in enhanced
      regeneration specificity. This information has been extended to the conduit
      model. The interposition of healthy nerve segments into conduits is proposed as a
      means of extending the length of successful nerve regeneration.

PMID- 8736679
TI  - Multivalvular disease.

PMID- 8736680
TI  - Etiology of valvular heart disease.
AB  - The incidence of congenital valvular heart disease has not significantly altered
      in recent decades. Major factors contributing to altered profiles of acquired
      valvular heart disease in the past few decades include an increased elderly
      segment of the population and increasing recognition of nonrheumatic forms of
      valvular heart disease. Mitral valve prolapse, and similar involvement of other
      valves, together with senile calcific aortic stenosis have emerged as the most
      common forms of valvular heart disease in developed countries. Body leanness and
      hypertension are additional etiological factors for senile calcific aortic
      stenosis. Severe calcification of a congenital bicuspid aortic valve continues to
      be an important cause of aortic stenosis in the elderly. Idiopathic degeneration
      of the aortic and mitral valves, apparently a different condition than mitral
      valve prolapse, has also become recognized. Despite a recent increase in the
      incidence of acute rheumatic fever in North America, rheumatic heart disease
      remains an infrequent cause of valvular heart disease in developed nations. Its
      incidence has diminished in the Middle East, but it is still frequent in
      underdeveloped countries. Intravenous drug abuse is increasing in importance as a
      cause of valvular heart disease in urban centers in the United States. Syphilitic
      heart disease is very rare.

PMID- 8736681
TI  - The management of mitral valve disease.
AB  - Clinical investigators continue to make significant advancements in the diagnosis
      and treatment of patients with mitral valve disease. The salutary effects of
      mitral balloon valvotomy for mitral stenosis and the development of a reasonable
      approach to the asymptomatic patient with chronic mitral regurgitation are
      examples of relevant research that affects clinical outcomes. Recent developments
      in the management of patients with mitral valve disease are reviewed.

PMID- 8736682
TI  - Aortic valve disease.
AB  - There have been several significant advances in our understanding of aortic valve
      disease over the past year. Recent studies suggest that "degenerative" valvular
      aortic stenosis is an active disease process rather than an inevitable
      consequence of aging. In the diagnostic evaluation of patients with aortic
      stenosis, detailed studies of the changes in valve area with changes in flow rate
      and the subaortic flow profile have been performed. In addition, the myocardial
      response to chronic pressure overload has been studied in further detail
      including gender differences in the response to chronic pressure overload. Aortic
      regurgitant severity can now be quantitated more precisely using simplified
      measures of regurgitant fraction based on Doppler and color flow imaging
      techniques. The optimal timing of surgical repair in chronic aortic regurgitation
      continues to be a topic of interest, with additional studies recommending
      surgical intervention prior to the development of an irreversible decrease in
      left ventricular contractility. Most importantly, two randomized trials of
      afterload reduction for preventing left ventricular dilation and symptom onset in
      aortic regurgitation have been performed, with the data supporting long-term
      afterload reduction in this patient group.

PMID- 8736683
TI  - Rheumatic heart disease.
AB  - Rheumatic heart disease seems in many ways emblematic of an older era in
      medicine, without any prospects of new development or change in the current era.
      Many new findings have come to light in the past few years regarding this
      illness, which has a relatively low prevalence in the United States. Not only
      have the diagnostic Jones criteria for acute rheumatic fever changed, but
      substantial advances have been made in the use of penicillin prophylaxis for
      recurrent rheumatic attacks, the use of mitral valve repair or reconstruction for
      rheumatic mitral regurgitation, the management of rheumatic, aortic, and mitral
      valve disease, and the application of balloon commissurotomy for mitral stenosis.
      This review details some of these advances.

PMID- 8736684
TI  - Diagnosis and management of prosthetic valve dysfunction.
AB  - Immediate and long-term prognosis of patients with prosthetic valves critically
      depends on prevention, rapid diagnosis, and optimal treatment of complications.
      This review describes the current practice in management of prosthetic
      dysfunction and discusses unresolved or controversial issues such as: what is the
      optimal anticoagulation regimen in both mechanical and bioprosthetic heart
      valves? Is thrombolysis superior to surgery in thrombotic valve obstruction? Is
      valve replacement superior to conservative therapy for prosthetic valve
      endocarditis? In addition, recently obtained data relating to the incidence of
      early and late mortality, thromboembolism, anticoagulation-related hemorrhage,
      valve thrombosis, hemolysis, paravalvular leakage, and the necessity and risk of
      reoperation are presented.

PMID- 8736685
TI  - Advances in surgical treatment of acquired valve disease.
AB  - After the first two decades of constant improvements in valve prostheses, no
      major advance has occurred since the mid 1980s. Hence, valve replacement remained
      the exchange of one disease for another. With minor and, for the most part,
      statistically nonsignificant variations, the spectrum of late valve-related
      complications remained unaltered and the few series published in the year under
      review brought no additional information of relevance. By contrast, in the past
      few years there has been a growing enthusiasm for the use of allografts,
      stentless porcine bioprostheses, and pulmonary autografts. Not only was there a
      surge of interest in the allografts as aortic valve substitutes, but in the past
      year there have also been several reports of use for whole or partial mitral or
      tricuspid valve replacement. On the other hand, stentless bioprostheses are also
      gaining increasing acceptance, and all major manufacturers of heart valve
      prostheses have models for use in different situations and with different
      techniques. Finally, the Ross operation is now being performed around the world.
      Despite these advances, valve repair still merits the preference of many
      surgeons. Mitral valvuloplasty preserves left ventricular function much better
      than valve replacement. By contrast, the results of aortic valve repair look much
      less impressive. Lastly, this work focuses on recent reports on special aspects
      of surgery for native or prosthetic valve endocarditis, especially with the use
      of allografts or autografts; on the results of valve surgery in elderly patients,
      a fast growing group; and on the controversial issues of anticoagulation in
      patients with artificial valves.

PMID- 8736686
TI  - Valvular disease in pregnancy.
AB  - Previously asymptomatic mitral stenosis can lead to remarkably sudden development
      of life-threatening pulmonary edema in pregnancy and the patients, often
      immigrants from the developing world, may be unaware that they have heart
      disease. Diagnosis and treatment need to be rapid and effective. Left ventricular
      outflow tract obstruction may also lead to trouble in pregnancy with the
      development of angina and left ventricular failure. Regurgitant valve disease is
      much better tolerated in pregnancy than valvular stenosis, but mitral valve
      repair, usually feasible for nonrheumatic prolapsing mitral valves, should be
      carried out before pregnancy if regurgitation is severe. The treatment of women
      with Marfan's syndrome who already have aortic root widening but desire children
      remains very difficult, both with regard to the mother's safety and in relation
      to the dominant inheritance of the condition. Advice to women with artificial
      valves desiring pregnancy remains controversial, with continuation of warfarin
      increasingly favored over transfer to heparin in Europe. The use of bioprostheses
      in young women anticipating future pregnancy is also fading due to mounting
      evidence of accelerated deterioration of such bioprostheses during pregnancy.

PMID- 8736687
TI  - Current status of heart transplantation.

PMID- 8736688
TI  - Selection and management of candidates for heart transplantation.
AB  - The increasing discrepancy between the donor hearts available and the number of
      patients with advanced heart failure underscores the need to optimize medical
      therapy and restrict the option of cardiac transplantation to patients with heart
      failure refractory to maximal conventional therapy. New medical and surgical
      therapies should be studied specifically in this population. The need for heart
      transplantation in ambulatory patients with severe heart failure is better
      assessed by the serial evaluation of objective measures of clinical stability and
      peak exercise oxygen consumption, than by assessment of standard risk factors at
      the time of patient referral. Among comorbidities which may preclude
      transplantation, psychosocial risk factors have recently undergone stricter
      scrutiny. The successful outcome of candidates for heart transplantation requires
      serial assessment and continuity of care by a dedicated team of health
      professionals specialized in heart failure and transplantation.

PMID- 8736689
TI  - Selection and management of cardiac allograft donors.
AB  - The selection of suitable donor hearts is essential for successful recipient
      outcome. Early allograft failure accounts for approximately 25% of deaths in
      heart transplantation recipients. The pool of donor organs that become available
      is inadequate to meet the ever increasing demand. Almost 30% of patients awaiting
      cardiac transplantation die before a suitable donor heart becomes available. The
      development of strategies aimed at expanding the donor pool are critically
      needed. To accomplish this goal it is important to improve donor management,
      prevent tissue injury following brain death, and attempt to correct donor organ
      dysfunction.

PMID- 8736690
TI  - The pathogenesis of cardiac allograft vasculopathy.
AB  - There has been an intensive effort in the past year to identify immunologic and
      nonimmunologic factors in the pathogenesis of cardiac allograft vasculopathy.
      Significant progress has been made regarding cell proliferation and cell death,
      with particular focus on cell growth factors, cell death factors, and their
      receptors. Endothelial cell injury and endothelin expression and production have
      been implicated in the development of cardiac allograft vasculopathy. A
      significant clinical association between dyslipidemia and cardiac allograft
      vasculopathy has been detected by intracoronary ultrasonography. Furthermore,
      proteoglycans are postulated to play an important role through lipoprotein
      proteoglycan interactions. The role of cytomegalovirus infection remains
      controversial. Immunosuppressive agents such as rapamycin and FK506 may
      contribute to a reduction of vasculopathy.

PMID- 8736691
TI  - Opportunistic infections in the cardiac transplant patient.
AB  - The risk of opportunistic infection in the cardiac transplant patient is
      determined by the interaction between the epidemiologic exposures that the
      patient encounters and the patient's net state of immunosuppression. The
      epidemiologic exposures include those encountered in both the community and the
      hospital, with the latter being more important as they usually occur at a point
      in time when the patient's net state of immunosuppression is at its highest. The
      net state of immunosuppression is a complex function whose major determinants are
      the immunosuppressive program and the presence or absence of infection with a
      group of immunomodulating viruses, particularly cytomegalovirus. Strategies for
      preventing opportunistic infection in this patient population are based on the
      following factors: technically impeccable surgery, precisely managed
      immunosuppression, environmental protection (particularly in the hospital), and
      the use of preventative antimicrobial strategies. These last are of two types,
      prophylactic and preemptive. The key point in both these approaches is to link
      the preventative strategy to the intensity of the immunosuppressive program and
      to target the antimicrobial program to the time period and patient group at
      greatest risk. For most opportunistic infections this is the time period 1 to 6
      months after transplantation (when viral infections are prevalent), and the small
      group of patients more than 6 months after transplantation who are chronically
      overimmunosuppressed because of rejection.

PMID- 8736692
TI  - New monoclonal antibodies.
AB  - Monoclonal antibody technology has become an important diagnostic and therapeutic
      tool in many areas of medicine, including the prevention and treatment of organ
      transplant rejection. The monoclonal antibody that has been most widely used
      clinically is OKT3, a murine monoclonal antibody directed against the CD3
      receptor on the surface of human T cells. In heart transplant recipients OKT3
      successfully reverses rejection refractory to conventional immunosuppression.
      Monoclonal antibodies that are partially of human origin reduce the problem of
      sensitization in human recipients. The production of a fully human Fab' that can
      be used in place of the whole monoclonal antibody is being actively investigated.
      Strategies designed to induce tolerance to the allograft will involve the
      combined administration of monoclonal antibodies and donor antigens.

PMID- 8736693
TI  - Induction of tolerance to cardiac allografts.
AB  - The ability to induce tolerance to alloantigens, and in the future xenoantigens,
      in vivo is essential to progress in transplantation. The immunosuppressive drugs
      available for use in clinical transplantation at present are capable of
      preventing or reducing the incidence of acute rejection in the first few months
      after transplantation, but they appear less effective at preventing chronic graft
      loss. The induction of tolerance to the histocompatibility antigens of the organ
      donor in the long term after transplantation would eliminate the need for long
      term administration of these nonspecific immunosuppressive drugs. This alone
      would have a major impact on the quality of life of patients with long-term
      surviving organ grafts by reducing the immunologic and nonimmunologic
      complications associated with long-term immunosuppressive therapy. The strategies
      for the induction of tolerance in the long term after transplantation, and more
      ambitiously before transplantation, that are currently being explored in a
      variety of experimental models are the subject of this review.

PMID- 8736694
TI  - Recent advances and the potential for clinical use of xenotransplantation.
AB  - The success of allotransplantation has paradoxically led to a shortage in the
      supply of organs required to meet the increasing demand. Xenografts represent a
      potentially infinite supply of good quality organs. Recent advances in the
      understanding of the immunobiology of xenograft rejection has spurred
      experimental approaches aimed at abrogating or suppressing human xenospecific
      immune responses. The limited supply of colony-bred nonhuman primates (baboons)
      makes it highly unlikely that this species will be of widespread use as a donor
      source. Therefore, the pig has been proposed as a realistic alternative donor.
      Delineation of the major pig xenoantigens recognized by natural human
      xenoreactive antibodies has led to the development of strategies aimed at
      depletion of antibodies or the prevention of their binding to xenogeneic
      endothelium. Recognition that antibody binding leads to endothelial cell
      activation and complement-mediated injury has led to the development of
      genetically modified pigs whose organs are potentially resistant to damage by
      human complement by virtue of the fact that their endothelial cells express
      membranebound human complement regulatory proteins. Finally, dissection of the
      relative contributions of humoral and cellular immune responses directed against
      xenografts from closely or distantly related species has permitted rational
      recommendations for the administration of immunosuppressive regimens.

PMID- 8736695
TI  - Valvular heart disease.

PMID- 8736696
TI  - Heart transplantation.

PMID- 8736697
TI  - Age-associated decrease in inositol 1,4,5-trisphosphate and diacylglycerol
      generation by 1,25(OH)2-vitamin D3 in rat intestine.
AB  - The hormonal form of vitamin D3, 1,25(OH)2-vitamin D3(1,25[OH]2D3), stimulates
      the breakdown of membrane phosphoinositides, generating inositol-1,4,5
      trisphosphate (IP3) and diacylglycerol (DAG) in a variety of cell systems.
      Several studies suggest that alterations in the receptor-mediated
      phosphoinositide cascade are involved in the pathophysiology of aging. Therefore,
      the formation of IP3 and DAG were determined under basal conditions and after
      stimulation with physiological concentrations of 1,25(OH)2D3 in duodenum from
      young (3-mo-old) and aged (24-mo-old) rats. The hormone induced a transient and
      biphasic formation of IP3 and DAG. Values obtained in young rats peaking at 15 s
      (51% and 42% above basal levels for IP3 and DAG, respectively) and at 3 min (90%
      and 74% above basal levels for IP3 and DAG, respectively) were significantly
      decreased in duodenum from senescent animals (IP3: +20% and DAG: +18% above basal
      level at 15 s; and IP3: +18% and DAG: +29% above basal level at 3 min). The
      1,25(OH)2D3-induced generation of DAG in both young and aged duodenum was
      effectively inhibited in the presence of neomycin, a phospholipase C (PLC)
      inhibitor, and was dependent on extracellular Ca2+. After the biphasic response,
      the levels of DAG generated by the hormone (10 min stimulation) remained
      elevated; the elevation occurred in the absence of IP3 production; and the
      elevated levels were not abolished by neomycin, implying that phospholipids other
      than phosphoinositides are the source of DAG. This 1,25(OH)2D3-dependent late
      phase of DAG generation was also diminished in aged animals. The precise
      molecular basis and the physiological significance of decreased liberation of IP3
      and DAG by 1,25(OH)2D3 in the aged rat duodenum remains to be determined.

PMID- 8736698
TI  - In vitro and in vivo growth inhibition of murine melanoma K-1735 cell by a
      dominant negative mutant alpha subunit of the Gi2 protein.
AB  - In murine and rat fibroblasts, activation of several G proteins (Gi2, Gq, G12)
      can stimulate cell growth or transformation, and can induce tumor formation in
      nude mice; contrastingly, inactivation of Gi2 inhibits fibroblast proliferation
      in vitro. We investigated whether it is possible to modulate malignant cell
      growth in vitro and in vivo through alteration of Gi2 protein function. To do so,
      we introduced mutated alpha subunits of Gi2 (alpha i2) in CL19 cells, a clone of
      the murine melanoma cell line K-1735. When we did this, a constitutively
      activated mutant (alpha i2-Q205L) and a dominant negative mutant (alpha i2-G204A)
      of alpha i2 were stably expressed in CL19 cells. We found that the in vitro
      motility of all alpha i2-transfected CL19 cells was increased; however,
      overexpression and alteration of the function of Gi2 did not increase metastasis
      formation by CL19 cells in nude mice. Expression of alpha i2-Q205L conferred a
      limited growth advantage to CL19 cells in vitro; in vivo, tumor formation and
      size, and overall survival of animals injected with CL19 cells expressing alpha
      i2-Q205L, were similar to controls. In contrast, expression of the inactive alpha
      i2-G204A mutant inhibited CL19 growth in vitro by at least 50% in all conditions
      tested, and mice injected with cells expressing the alpha i2-G204A mutant showed
      delayed tumor formation, reduced tumor size, and longer survival. We conclude
      that Gi2 proteins contribute to malignant cell growth, and more importantly, that
      inactivation of Gi2 proteins can inhibit proliferation of melanoma cells and
      possibly of other malignant cells both in vitro and in vivo.

PMID- 8736699
TI  - Calcium controls second-messenger signalling in olfactory cilia.
AB  - The increase in intracellular calcium concentration elicited by odorant
      stimulation seems to be involved in down-regulating the responsiveness of
      olfactory neurons to subsequent stimuli. The present study suggests that this
      regulatory effect may be due to a calcium-dependent attenuation of the olfactory
      signalling cascade; the odor-induced cyclic adenosine monophosphate (cAMP)
      response in olfactory cilia is diminished by calcium in a dose-dependent manner.
      This reduced cAMP signal is not due to an activation of phosphodiesterases by
      elevated calcium levels, but rather seems to be mediated by the inhibition of
      adenylate cyclase by calcium ions.

PMID- 8736700
TI  - The dual role of S-nitrosoglutathione (GSNO) during thymocyte apoptosis.
AB  - Nitric oxide (NO) is known to regulate redox-sensitive signalling pathways in
      physiology and pathophysiology. Depending on its concentration, the NO-releasing
      compound S-nitrosoglutathione (GSNO) causes negative and positive regulation of
      thymocyte apoptosis. At levels below 0.6 mM, GSNO produces deoxyribonucleic acid
      (DNA) laddering, which is inhibited by activation of protein kinase C (PKC),
      cycloheximide treatment, and calcium chelation. Higher concentrations of the NO
      donor (1-2 mM) suppress thymocyte apoptosis initiated by the classical agonist
      dexamethasone. Inhibition of apoptosis by NO is analogous to the action of the
      thiol-blocking compound N-ethylmaleimide (NEM) and the glutathione-S-transferase
      substrate 1-chloro-2,4-dinitrobenzene (CDNB). Inhibition of apoptosis results
      from thiol modification of critical proteins in response to NO treatment.
      Depending on the concentration, GSNO can be involved either in toxic or in
      protective signalling in thymocyte biology.

PMID- 8736701
TI  - Arachidonic acid stimulates the intrinsic activity of ubiquitous glucose
      transporter (GLUT1) in 3T3-L1 adipocytes by a protein kinase C-independent
      mechanism.
AB  - Exposure of adipocytes to arachidonic acid rapidly enhanced basal 2-deoxyglucose
      uptake, reaching maximal effect at approximately 8 hr. Insulin-stimulated 2
      deoxyglucose uptake was not altered over the experimental period. While the short
      term (2-h exposure) effect of arachidonic acid was negligibly influenced by
      cycloheximide, the enhancement of glucose transport by long-term (8-h) exposure
      to arachidonic acid was markedly decreased by the simultaneous presence of
      protein-synthesis inhibitors, implying that the short-term and long-term effects
      of arachidonic acid may involve distinct mechanisms. Immunoblot analysis revealed
      that 8-h but not 2-h exposure to arachidonic acid increased the content of the
      ubiquitous glucose transporter (GLUT1) in both total cellular and plasma
      membranes. The insulin-responsive glucose transporter (GLUT4), on the other hand,
      was not affected. Following 2-h exposure to arachidonic acid, kinetic studies
      indicated that the apparent Vmax of basal 2-deoxyglucose uptake was more than
      doubled, while the apparent Km for 2-deoxyglucose remained unchanged. Protein
      kinase C (PKC) depletion by pretreating cells with 4 beta-phorbol 12 beta
      myristate 13 alpha-acetate (PMA) for 24 h had little influence on the subsequent
      enhancing effect of arachidonic acid on 2-deoxyglucose uptake. In addition, PMA
      was able to stimulate 2-deoxyglucose uptake in arachidonic-acid-pretreated cells
      with similar increments as in non-treated cells. Thus, our data seem to suggest
      that arachidonic acid may enhance the intrinsic activity of GLUT1 by a PKC
      independent mechanism.

PMID- 8736702
TI  - Intricate regulation of nitric oxide synthesis in neurons.
AB  - There is little doubt that nitric oxide (NO) is one of the most important second
      messengers yet to be discovered, particularly in relation to its diverse roles in
      the regulation of neuronal function. As expected, synthesis of such a
      multifunctional molecule has to be under very tight control. For example, there
      is evidence that the rate of production of NO in neurons is regulated by several
      second messengers and their related protein kinases. NO by itself is also able to
      elicit negative feedback on the activity NO synthase (NOS) to attenuate its own
      rate of synthesis. Furthermore, NO modulates the release of neurotransmitters and
      alters the sensitivity of receptors that are coupled to stimulation of its
      synthesis. In healthy neurons, all of these intricate mechanisms are expected to
      cross-talk in harmony to result in the generation of optimal amounts of NO.

PMID- 8736703
TI  - H-89 inhibits collagenase induction by phorbol ester through a mechanism that
      does not involve protein kinase A.
AB  - Cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) regulates
      the activity of growth-factor-induced pathways at the level of cytoplasmic
      kinases and nuclear transcription factors. We observed that H-89, an inhibitor of
      PKA, induced mitogen-activated protein (MAP) kinase activity in a 12V-ras
      transformed fibroblast cell line. In contrast, H-89 inhibited phorbol-ester
      mediated induction of MAP kinase, junB messenger ribonucleic acid (mRNA), and
      collagenase mRNA in these cells. Phorbol-ester stimulation of a collagenase
      promoter reporter construct was also inhibited by H-89. However, stimulation of
      the collagenase promoter was not inhibited by overexpression of the PKA
      inhibitory protein PKI. These data suggest that H-89 inhibits the activity of an
      enzyme required for phorbol-ester induction of collagenase mRNA, but that this
      inhibition does not occur at the level of PKA.

PMID- 8736704
TI  - Cellular signalling: the role of the peroxisome.
AB  - This article reviews the role of the peroxisome in cellular signalling, with
      particular emphasis on the unique contributions of this organelle to the complex
      regulatory inter-relationships of cellular processes within the mammalian
      organism. Among the topics covered are the close alignments between the
      signalling systems governing peroxisome proliferation and those of the steroid
      hormone/thyroid hormone/vitamin D nuclear-receptor superfamily; the regulation of
      the permeability of the peroxisomal membrane; the involvements of
      lysophosphatidic acid as an intra- and inter-cellular messenger; the special role
      of the phosphatidylcholine cycle and its derivative messengers in relation to
      peroxisomal metabolism; peroxisomal contributions to the regulation of oxygen
      free radical levels in tissues and the significance of these radicals as second
      messengers; the evidence of peroxisomal influences on inter-cellular signalling
      from metabolic turnover studies; modifications of the regulatory significance of
      fatty acids by the peroxisome; the commonalities in metabolic relationships
      between the peroxisome and other cellular organelles; and regulatory shuttles
      associated with peroxisomal function. It is concluded that the peroxisome
      displays several significant interconnections with the cellular-signalling
      apparatus, that it is capable of imprinting a characteristic influence on the
      regulatory network in the cell, and that the contributions of this organelle
      deserve greater consideration in future investigations of cell-signalling
      phenomena.

PMID- 8736705
TI  - GTP binding to Gs does not promote subunit dissociation.
AB  - The stimulatory G protein (Gs) mediates activation of adenylyl cyclase. Gs is a
      heterotrimeric protein (alpha beta gamma) that is activated when guanosine
      triphosphate (GTP) or a non-hydrolyzable GTP analogue displaces tightly bound
      guanosine diphosphate (GDP) from the guanine nucleotide-binding site of the alpha
      subunit (Gs alpha). Divalent cations such as magnesium are also required for Gs
      activation. Subunit dissociation can accompany Gs activation and is thought to be
      critical for this process. We investigated the effects of MgCl2 and various
      purine nucleotides on Gs-subunit dissociation and activation. Subunit
      dissociation was assayed by measuring the amount of G protein beta-subunit that
      was co-precipitated by Gs alpha-specific antiserum. Gs activation was determined
      by its ability to reconstitute adenylyl cyclase activity in S49 cyc-membranes
      that lack Gs alpha. High concentrations of MgCl2 caused bound GDP to dissociate
      from Gs and inactivated the protein unless high concentrations of GDP or GTP were
      present in solution. MgCl2 caused a concentration-dependent dissociation of Gs
      subunits. GTP gamma S (a non-hydrolyzable GTP analogue) shifted the MgCl2
      concentration-response curve for subunit dissociation to lower concentrations of
      MgCl2, suggesting that GTP gamma S promoted subunit dissociation. On the other
      hand, GDP and GTP were equally effective in shifting the curve to higher
      concentration of MgCl2. These results suggest that GTP, the compound that
      activates Gs in vivo, was no more effective at promoting Gs subunit dissociation
      than was GDP.

PMID- 8736706
TI  - Mechanistic hypotheses for the activation of G-protein-coupled receptors.
AB  - G-protein-coupled receptors (GPCR) play an important role in the functioning of
      the nervous and endocrine systems. Intensive efforts devoted to mutational
      analyses of GPCR have greatly enhanced our understanding of the receptor-G
      protein signalling pathway. Nonetheless, the lack of receptor structural data
      mandates that the mechanism of receptor activation can only be probed indirectly
      through hypothesis testing. Mechanistic models at two different levels, a
      thermodynamic model and a structural model, are reviewed here. A general
      thermodynamic model can be used as a framework for analyzing macroscopic
      experimental data, while a probability function based on a helical-rotation model
      can potentially provide a link between microscopic conformational changes and
      macroscopic rate constants and equilibrium constants. Conformational induction
      and conformational selection are two inseparable consequences of the receptor
      binding system. Mechanistic models based on the integration of mutational data,
      spectroscopic data, and model simulation will form a foundation upon which
      further experiments can be designed, and consideration of both thermodynamic and
      structural principles will provide coherent insights into the receptor-activation
      process.

PMID- 8736707
TI  - G proteins in adipocytes and preadipocytes: characterization, subcellular
      distribution, and potential roles for Gi2 and/or Gi3 in the control of cell
      proliferation.
AB  - Guanosine triphosphate (GTP)-binding protein subunits were studied by immunoblot
      analysis in particulate fractions from mature adipocytes, confluent
      preadipocytes, and in vitro-differentiated preadipocytes. Mature adipocytes
      express Gi alpha 1, Gi alpha 2, Gi alpha 3, Go alpha, Gq/11 alpha, G13 alpha and
      the long and short isoforms of Gs alpha, but no Gz alpha or G12 alpha. Confluent
      and differentiated preadipocytes differ in having a higher content of Gi alpha 3
      and G13 alpha and expressing G12 alpha. In contrast, they lack Gi alpha 1, Go
      alpha, and the short from of Gs alpha. The G-protein alpha subunits Gi alpha 2,
      Gs alpha (long isoform), and Gq/11 alpha, and G-protein beta subunits were
      unchanged throughout the differentiation process. By immunoblot and indirect
      immunofluorescence studies on confluent preadipocytes, we showed that Gi alpha 2
      is present in the endoplasmic reticulum and marginally in plasma membranes and
      nuclei. In contrast, antibodies to Gi alpha 3 stained the Golgi apparatus. The
      role of G proteins on preadipocyte proliferation was studied using Bordetella
      pertussis toxin. Exposure of growing cells to this toxin in the presence of fetal
      calf serum (FCS) decreased [3H]thymidine incorporation by 40% and induced a 40%
      increase in doubling time. This resulted in a 30% decrease in cell number per
      well after 48 h. These effects of B. pertussis toxin did not appear to be related
      to an increase in cyclic adenosine monophosphate (cAMP) concentration, because
      forskolin had the opposite effect on cell proliferation. Finally, B. pertussis
      toxin prevented serum-induced Raf1 association to the plasma membrane, possibly
      by disrupting FCS-induced G beta gamma effects on the Ras/Raf1 pathway. Since Go
      alpha and Gi alpha 1 subunits were absent in preadipocytes, we conclude that Gi2
      and/or Gi3 proteins transduce some mitogenic signals of FCS through release of G
      beta gamma subunits. The subcellular distribution of Gi alpha 2 and Gi alpha 3
      suggests that part of their functions result from interactions with components
      other than the plasma membrane.

PMID- 8736708
TI  - Effects of ambulation on foot oxygen tension in limbs with peripheral
      atherosclerosis.
AB  - As walking a few steps increases the arteriovenous pressure difference for blood
      flow through the feet, we studied the effect of a brief period of walking on
      transcutaneous oxygen tension (tcPO2). Foot tcPO2 was measured using Clarke type
      electrodes before, during and after a brief period of repetitive walking on the
      treadmill in 15 patients with various degrees of arterial obstruction. TcPO2 was
      significantly higher during walking, than while standing on the treadmill, in
      limbs with severe disease manifested by toe systolic pressure <30 mmHg (mean
      change 0.7 kPa or 5 mmHg, P=0.001). Also, supine tcPO2 was significantly higher
      following periods of walking than before in limbs with toe pressure both below
      and above 30 mmHg (mean change 1.5 kPa or 11 mmHg, P<0.001). The results indicate
      that a brief period of walking increases skin oxygenation. Regimens of such
      exercise may promote healing in some limbs with arterial disease.

PMID- 8736709
TI  - Cardiac sympathovagal balance during sleep apnea episodes.
AB  - The main acute cardiovascular effects of obstructive sleep apnea syndrome (OSAS)
      are elevation of blood pressure and reflectory bradycardia, which are followed by
      an abrupt tachycardia on resumption of breathing. This haemodynamic instability
      is related to hypoxemia and arousal, and may lead to increased risk from cardiac
      arrhythmias and sudden cardiac death, as well as to the development of chronic
      arterial hypertension, in these patients. The aim of this study was to apply
      frequency domain analysis of heart rate variability (HRV) measured from
      continuous electrocardiogram (ECG) recordings to evaluate how cardiac autonomic
      function, and especially cardiac sympathovagal tone, changes during sleep apnea
      episodes. We identified 41 apneas leading to more than 4%-unit arterial oxygen
      desaturation in 12 patients (11 men, 1 woman (correction for women), age range 27
      67 years). Frequency domain analysis of HRV was performed from ECG recordings
      using 4 min epochs starting 20 min before apnea began and lasting 20 min after
      the beginning of apnea. The mean (+/-SEM) fall in oxygen saturation during the
      apnea was 6.8 +/- 0.6%-units. While high frequency band (HF, reflects cardiac
      vagal activity) remained unchanged, low frequency band (LF, mainly sympathetic
      activity) showed a constant increase, leading to significant change in the
      sympathovagal balance (LF/HF ratio). In conclusion, concordantly with previous
      peripheral sympathetic-nerve recordings, frequency domain analysis of HRV is able
      to detect sympathetic activation during sleep apnea episodes, leading to marked
      change in the sympathovagal balance.

PMID- 8736710
TI  - The concentrations of free amino acids in human liver tissue obtained during
      laparoscopic surgery.
AB  - The concentrations of the free amino acids in individual tissues gives
      information concerning amino acid, energy and protein metabolism. In muscle and
      intestinal mucosa, different metabolic states are distinctly characterized by an
      altered free amino acid pattern. Furthermore, the patterns are quite different in
      individual tissues. So far, liver tissue has not been investigated systematically
      in this respect. The aims of this investigation were to establish a standardized
      sampling procedure for liver tissue during laparoscopic surgery and to
      characterize the free amino acid concentrations in human liver tissue. Aspartate
      was the most abundant amino acid in the liver, followed by taurine, glutamine,
      glutamate, glycine and alanine. These six, and most abundant, amino acids
      constitute 90% of the total hepatic amino acid concentration. In the future,
      liver tissue sampling during laparoscopic surgery may be used as a model for
      investigating the influence of nutrition and hormones on hepatic amino acid and
      protein metabolism in man.

PMID- 8736711
TI  - Improved gas exchange during exercise after weight loss in morbid obesity.
AB  - The aim of this study was to determine the effect of weight loss induced by 6
      weeks very-low-calorie-diet (VLCD) and behavioural intervention on pulmonary gas
      exchange during exercise in non-smoking morbid obese (BMI>40 kg/m2) otherwise
      healthy patients. Seven obese patients underwent a maximal bicycle ergometer test
      with continuous analysis of expired air and arterial blood sampling before and
      after a mean weight loss of 18% (25.7 kg, range: 10-50 kg). Body mass index (BMI)
      decreased with weight loss from 46.6 (6.3) kg/m2 to 38.0 (4.7) kg/m2 (P<0.01).
      Oxygen consumption (VO2) at low and submaximal exercise levels decreased after
      weight reduction, but the change was not statistically significant. The peak
      oxygen consumption related to body weight (VO2/kg) increased 22% from the initial
      16.2 (3.6) ml/min/kg to 19.8 (3.1) ml/min/kg (P<0.05). Decrease in VCO2 was
      significant at submaximal exercise level. Ventilatory equivalent for CO2
      increased significantly after weight reduction (P<0.05). Standing up and light
      exercise resulted in a significant increase in the mean arterial oxygen tension
      (PaO2) (P<0.05) and a significant decrease in the mean alveolar-arterial
      difference P(A-a)O2 (P<0.05) when compared to supine values. The mean increase in
      PaO2 with weight loss was not significant. The peak P(A-a)O2 decreased
      significantly after weight reduction. In conclusion, weight reduction induced by
      VLCD and behavioural intervention without exercise therapy can improve gas
      exchange during exercise in morbid obesity. Increased wasted ventilation, and a
      tendency to alveolar hyperventilation, after weight loss may reflect a delay in
      the adaptation of regulation of breathing to rapid weight loss.

PMID- 8736712
TI  - Three-dimensional cross-sectional velocity distribution in the ascending aorta in
      cardiac patients.
AB  - Knowledge of the distribution of velocities across the ascending aorta is
      important for measurements of cardiac output; for understanding the function of
      normal and diseased valves and for the evaluation of prosthetic valves. The aim
      of this study was to investigate, in detail, the spatial distribution of axial
      velocities in the human ascending aorta, covering a nearly complete cross-section
      of the lumen in a time continuous modus. During open-heart surgery, blood
      velocities in the ascending aorta were mapped in 10 patients. All patients had
      aortic valves with no significant clinical evidence of disease. Pulsed Doppler
      ultrasound technique was used to measure blood velocity using an intraluminal
      probe with a 1 mm, 10 MHz crystal connected to a position-sensitive device. The
      distribution of blood velocity in the aorta 6-8 cm above the valve was
      characterized by a skewed and irregular peak systolic flow, with maximum velocity
      posteriorly. There was a positive correlation (r=0.854, P<0.002) between the
      maximum skewness slope and the stroke volume. Significant retrograde flow was
      recorded in all patients in the left posterior part of aorta in late systole and
      early diastole. The rotation of the point of maximal velocity was anticlockwise
      in six patients, clockwise in three and alternating in one. The present study
      shows that there is a considerable individual variation in the velocity
      distribution in the ascending aorta, with no plane symmetric features, and that
      large sampling volumes are required for reliable estimates of mean velocity.

PMID- 8736713
TI  - Heat-washout: a new method for measuring cutaneous blood flow rate in areas with
      and without arteriovenous anastomoses.
AB  - A new method, the heat-washout method, for measuring total cutaneous blood flow
      rate is introduced. The measurements were performed with a transcutaneous (tc)
      PO2-electrode that is capable of heating and measuring local temperature, and it
      is constructed with a thermostatically controlled cap. The probe was heated
      electrically to a selected temperature 2-10 degrees above normal skin
      temperature. When the temperature was stable, the heating element was turned off,
      and the temperature was registered every 10 s until a stable baseline
      temperature, Tb, was obtained. Tb was subtracted from the registered temperatures
      giving deltaTs that were plotted in a semilogarithmic diagram. The heat-washout
      was monoexponential, and the slope was used for calculating blood flow rate in
      accordance with the principle of Kety, using a known partition coefficient. The
      method was applied to the forearm in two subjects, and the results were compared
      to blood flow rates obtained simultaneously by the 133Xe-washout method in the
      same area. The equation of the regression line was y = 2.5 + 0 x 968X and the
      correlation coefficient was 0 x 986 at temperature levels of 37-45 degrees C. In
      the pulp of the thumb, blood flow rates, in arteriovenous anastomoses, were
      estimated in two subjects by subtracting the capillary blood flow rate, measured
      by 133Xe-washout, from the total cutaneous blood flow rate, measured by heat
      washout. Due to a relatively low diffusions coefficient for 133Xe compared to
      heat, 133Xe cannot be used for measurement of blood flow rate in arteriovenous
      anastomoses.

PMID- 8736714
TI  - Blood flow rate in arteriovenous anastomoses and capillaries in thumb, first toe,
      ear lobe, and nose.
AB  - Measurements of blood flow rate in the pulp of the thumb, the first toe, the ear
      lobe, and the nose were performed using the heat-washout method, and the 133Xe
      washout method under orthostatic changes in humans. Blood flow rate measured by
      the heat-washout method in the thumb was about 127.5 ml (100 g x min)-1 at heart
      level in two subjects, (n=10), and in the pulp of the first toe in 6 subjects
      (n=12) 49.3 ml (100 g x min)-1 at heart level. Above heart level blood flow rate
      decreased with the falling pressure head, and 50 cm below heart level blood flow
      remained unchanged compared to heart level. The arterioles supplying the
      capillaries in this region showed autoregulation of blood flow to 50 cm above
      heart level, but a veno-arteriolar reflex was not present. Blood flow rate in the
      ear lobe and on the side of the nose showed a similar pattern of reaction, with a
      blood flow rate in the arteriovenous anastomoses of about 100 ml (100 g x min)-1
      in sitting position.

PMID- 8736715
TI  - The transport of phosphate between the plasma and dialysate compartments in
      peritoneal dialysis is influenced by an electric potential difference.
AB  - Six kinetic models of transperitoneal phosphate transport were formulated and
      validated on the basis of experimental results obtained from 22 non-diabetic
      patients undergoing peritoneal dialysis. The models were designed to elucidate
      the presence or absence of diffusive, non-lymphatic convective, and lymphatic
      convective phosphate transport. Calculations allowed for a 20% protein binding of
      phosphate. The validation procedure demonstrated that only diffusive and non
      lymphatic convective phosphate transport mechanisms were identifiable. A
      lymphatic convective phosphate transport mechanism was not identifiable.
      Furthermore, it was demonstrated that the electrochemical gradient between plasma
      water and dialysate favours the diffusive phosphate transport, and both electric
      and chemical potentials must be taken into account in calculations of the
      transperitoneal phosphate transport.

PMID- 8736716
TI  - Smoke-derived nitric oxide and vascular prostacyclin are unable to counteract the
      platelet effect of increased thromboxane formation in healthy female smokers.
AB  - The incidence of cigarette smoking tends to be higher in women, justifying
      directed studies on smoke-related mechanisms of cardiovascular disorder in
      females. Platelet activity plays an important etiological role in several
      settings of cardiovascular disease. Cigarette smoking facilitates platelet
      formation of proaggregatory thromboxane A2. However, cigarette smoke contains
      nitric oxide (NO), which has antiplatelet activity. Furthermore, the formation of
      anti-aggregatory prostacyclin (PGI2) may be higher in smokers than in non
      smokers. Hence, the concerted action of NO and PGI2 on platelet activity in
      smoking females is important to elucidate. The metabolites of TxA2, NO, and PGI2,
      as well as cyclic guanosine 3':5'-monophosphate (cGMP; second messenger for NO in
      the platelets) and cyclic adenosine 3':5'-monophosphate (cAMP; second messenger
      for PGI2 in the platelets), were analysed in 23 healthy female smokers (daily
      consumption 11-20 cigarettes per day) and in 26 matched non-smokers. The urinary
      excretion of 2,3-dinor TxB2 (metabolite of TxA2) was considerably higher in
      smokers than in non-smokers (177 vs. 72 pg/mg creatinine, respectively; P<0.001).
      Plasma and urinary levels of nitrate (metabolite of inhaled NO) did not differ
      between the groups. Plasma and urinary cGMP were slightly increased (252 vs. 193
      nmol/L; P<0.05 and 0.63 vs. 0.51 micromol/24 h; P<0.05, respectively) in smokers
      compared to non-smokers, while platelet cGMP was lower in smokers than in non
      smokers (81 vs. 10.3 pmol/10(6) platelets, respectively; P<0.05). The urinary
      excretion of 2,3-dinor-6-keto-PGF1a (metabolite of PGI2) did not differ between
      the groups. Platelet or urinary cAMP did not differ between the groups either,
      while plasma cAMP was lower in smokers than in non-smokers (19.2 vs. 26.2 nmol/l,
      respectively; P<0.001). In healthy female smokers NO is not absorbed from the
      inhaled smoke, and endothelial PGI2 formation is not enhanced to counterbalance
      the increased platelet formation of proaggregatory TxA2.

PMID- 8736717
TI  - Relationships between field fitness test and basal serum testosterone and
      cortisol levels in soccer players.
AB  - The aim of this study was to investigate the existence of a relationship between
      performance capacities and blood levels of testosterone (T) and cortisol (C).
      Thirty-two professional soccer players volunteered for the study. Morning levels
      of hormones were plotted against results of maximal vertical jump with a
      preparatory counter-movement (CMJ), 30 m running, and Cooper's 12-min running
      test. The serum T was positively related to both CMJ and average running speed
      (r=0.43 and r=0.47, respectively). Serum levels of C and T were in negative
      correlation (r= -0.40 and r= -0.49, respectively) with the results of Cooper's
      test. It was concluded that athletes with better explosive strength and sprint
      running performances have a higher basal level of testosterone. The results
      suggest a relationship between testosterone production and development of fast
      twitch muscle fibres in athletes.

PMID- 8736718
TI  - Electrodermal activity reveals respiratory and slower rhythms of the autonomic
      nervous system.
AB  - Electrodermal Activity (EDA) was measured in 55 subjects during (1) an alarm
      reaction, (2) mental load, and (3) physical load. In 34 subjects, not only was a
      transient response observed, but also, oscillatory patterns characterizing short
      term variations of EDA. The durations of these oscillations varied between 3-16
      s. Most commonly, they were approximately within the frequency range of
      respiration, or lower, at about 0.1 Hz. The EDA-rhythms were also related to the
      arterial blood pressure. They were, however, not strictly synchronized with
      respiration or with the blood pressure waves. We conclude that assessment of EDA
      in combination with fluctuations of the heart rate, and also, if possible,
      arterial blood pressure, may turn out to be a useful tool in the evaluation of
      the interaction between different regulatory processes that are realized by the
      common brainstem system.

PMID- 8736719
TI  - Male contraception.
AB  - With the powerful tools of molecular investigation, the last decade has witnessed
      the most remarkable scientific advance in our history, yet no new leads for male
      contraception have been forthcoming. All the likely methods of male contraception
      discussed above were derived from relatively 'old' physiological principles or
      serendipitous observations. The increasing gap between fundamental research (in
      the control of mammalian spermatogenesis) and the lack of clinical application
      are a testament to the low public funding priority afforded to male reproduction
      and the unwillingness of the pharmaceutical industry to invest in male
      reproductive research and development. Yet amidst such an unfavourable setting
      and with very limited support, it is heartening to note that the prospects of
      introducing a new systemic method for male contraception into the market by the
      end of this millenium has been greatly enhanced. Thus the results of recent
      studies have confirmed the contraceptive efficacy of sex steroid-induced
      oligozoospermia and unexpectedly revealed an ethnically distinct pattern of
      susceptibility to the hormonal suppression of spermatogenesis. Thus, Asian men
      are more responsive than are caucasian, and long-acting testosterone esters now
      being tested in that most densely populated part of the world may well hasten the
      large-scale application of this method. This is probably the most effective way
      to correct the misconceptions that men are unwilling or disinterested in sharing
      in family planning options with their partners. Together with the increased
      acceptance of novel non-surgical and reversible methods of vas deferens occlusion
      and the availability of improved non-latex condoms, the currently unfulfilled
      contraceptive needs of millions of men can be increasingly met in future years.
      The consequent increase in overall contraceptive prevalence could well make the
      telling difference between demographic catastrophe and maintaining good quality
      existence. Politicians, scientists and industrialists need to wake up to their
      responsibilities and the opportunities offered by this untapped resource and
      market potential.

PMID- 8736720
TI  - Post-partum contraception.
AB  - The choice of a post-partum contraceptive method depends on many factors,
      including the need for a temporary versus a permanent method, the infant feeding
      choice and the extent to which informed consent is made prior to delivery. For
      maximum protection, the non-breast-feeding woman should be protected from the
      fourth week post-partum, even if that means using a temporary method, such as
      condoms or spermicides, until her method of choice is procured. Combined
      oestrogen/progestin methods should be avoided by all women for 2-3 weeks to avoid
      elevating the risk of thromboembolism. Preparations containing oestrogen should
      be avoided altogether during lactation because they have been associated with a
      reduction in milk production. POPs, implants and injectables are appropriate
      regardless of infant feeding choice. They can be administered immediately post
      partum in bottle-feeding women, but should ideally be postponed for 6 weeks in
      breast-feeding women. It is best to insert IUDs within 10 minutes of delivery of
      the placenta, in order to minimize the risk of IUD expulsion. Insertion
      immediately after expulsion of the placenta requires special training, and
      expulsion rates are reduced with the insertion experience of the practitioner.
      Breast-feeding is not associated with an increase in IUD expulsion or uterine
      perforation, and it is associated with fewer removals for bleeding or pain. Tubal
      sterilization is safe, convenient and cost-effective when performed immediately
      after delivery, but it requires extensive counselling and fully informed consent
      prior to the onset of labour to avoid potential regret over post-partum tubal
      ligation. If the procedure is performed immediately, any effect on the
      establishment of lactation may be minimized. LAM is a method that can only be
      used by breast-feeding women. It may prove to be a useful way to time the
      commencement of a second, less temporary contraceptive method. Natural family
      planning methods require a period of abstinence for the establishment and
      identification of the new symptoms of fertility. When LAM is used during this
      interval, the need for abstinence may be reduced significantly for breast-feeding
      women. Breast-feeding provides health benefits for the woman and her infant, as
      well as the best possible nutrition for the baby. The International Planned
      Parenthood Federation (1990) (among others) recommends that, 'As far as is
      practicable, all women should be advised and encouraged to breastfeed fully'. The
      infant feeding decision affects the choice of a contraceptive method, and this is
      an important reason for the woman's physician to be interested in her infant
      feeding choice.

PMID- 8736721
TI  - Contraception with anti-progesterone.
AB  - Anti-progesterones have potential as contraceptives, acting either by the
      inhibition of ovulation or the inhibition of endometrial development. Clinical
      studies have shown that once-a-month treatment with Mifepristone in the early
      luteal phase is an effective contraceptive method, and that emergency post-coital
      contraception with Mifepristone is at least as effective as other methods
      currently used. Recent studies indicate that the endometrium is more susceptible
      to Mifepristone than are the hypothalamic and pituitary regions, and it may
      therefore be possible to develop a new contraceptive method based on low daily or
      once-weekly doses of Mifepristone that does not influence ovarian function.

PMID- 8736722
TI  - Modern intra-uterine devices.
AB  - Modern intrauterine devices (IUDs) provide effective, safe and long-term
      contraception and could be recommended to most women. The mechanism of action of
      an IUD is still not fully understood, but most recent research suggests that
      copper-IUDs as well as hormone-releasing intrauterine systems (IUSs) prevent
      conception. In women in mutually monogamous relationships the risk of PID is low
      and related to the insertion procedure. IUD/IUS use should be discouraged if
      there is a suspicion of increased risk of sexually transmitted disease. The risk
      of ectopic pregnancy is extremely low if modern, highly effective IUDs/IUSs are
      used. Copper-IUDs increase menstrual blood loss by around 50%, whereas hormone
      releasing IUSs substantially reduce menstrual blood loss. Careful patient
      selection and counselling are the most important tools in order to provide
      acceptable and safe IUD use.

PMID- 8736723
TI  - Contraceptive vaccines.
AB  - The basic principle of a contraceptive (or anti-fertility) vaccine is to use the
      body's own immune defence mechanisms to provide protection against an unplanned
      pregnancy. Factors such as: economic production, convenience of use, relatively
      long-lasting but reversible action, low failure rate, and the avoidance of
      mechanical devices or exogenous hormones make this approach a potentially
      attractive option for family planning programmes in both developing and developed
      countries. The major efforts in research and development have involved the
      prospect of active immunization against specific antigens of sperm, ovum, zygote
      and early embryo, and the pregnancy hormone hCG. Several anti-hCG vaccines have
      entered clinical trials and show promising results. These vaccines operate by
      preventing or interrupting pregnancy at the peri-implantation stage probably by
      neutralizing the luteotrophic action of hCG. The most refined vaccine is one
      directed against the unique C-terminal peptide on the beta-subunit of hCG. This
      vaccine provokes antibodies that are specific for hCG and do not cross react with
      hLH. Future research efforts aim to optimize the anti hCG approach, utilize new
      vaccine delivery systems, and broaden the spectrum of target antigens of
      potential utility for contraceptive vaccines.

PMID- 8736724
TI  - New hormonal methods of contraception.
AB  - Three types of new contraceptive delivery system have been discussed in this
      chapter. Each have novel methods of delivery and may be acceptable to certain
      groups of women. It is clear that subdermal contraceptive implants are extremely
      useful as a long-term method of contraception, and provided insertion occurs
      correctly, removal will then be easy. The second-generation implants using a
      single rod, compared with the first-generation ones using six capsules, would
      appear to offer advantages both to the patient and in relation to the training of
      medical and paramedical personnel who have to fit the subdermal implant. The main
      disadvantage is the incidence of irregular bleeding, which, by and large, can be
      overcome by pre-insertion counselling and by time. The second method of delivery,
      vaginal rings, offers high patient acceptability, but a usable ring for
      contraception has as yet to be developed. Two approaches appear to be the use of
      a continuous progestogen-only ring, or a combined ring releasing oestrogen and
      progestogen with a 21-day-in, 7-day-out cycle of use. Ongoing studies will
      indicate whether vaginal lesions are significant or related to the flexibility of
      the ring. If these studies prove satisfactory, further development of the vaginal
      rings, both as an alternative method for interval use or as a specific postpartum
      form of contraception using progesterone-releasing rings, will be developed.
      Significant developments in the use of a combined monthly injectable have led to
      the release of two preparations, Cyclofem and Mesigyna, which are now available
      in many countries. This combined approach offers a significant reduction in
      amenorrhoea rates and unacceptable bleeding, the majority of women having
      acceptable menstrual patterns even during the first 3 months of use. All three
      methods have low and acceptable rates of pregnancy, the lowest being seen with
      the subdermal implants and with combined monthly injectables. Due to the length
      of action of subdermal implants, these may find a niche for women wishing to use
      a long-acting method and not wishing to be sterilized. They also provide a useful
      method where medical intervention is not available on a regular basis. Monthly
      injectable preparations can be given by paramedical personnel, and introductory
      studies have indicated that in developing and developed countries, they are
      highly acceptable. All three methods offer an increased choice for women and safe
      and effective methods of contraception.

PMID- 8736725
TI  - Sterilization.
AB  - Sterilization is accepted as a permanent method of contraception by many couples
      in the world. Female sterilization is more widely used than male sterilization,
      but the latter is used by many couples in developed countries. The most widely
      used methods for female sterilization are simple tubal ligation, electrocautery
      of the fallopian tubes, and occlusion of the tubes by Hulka or Filshie clips or
      Falope rings. These procedures may be carried out either by minilaparotomy or by
      laparoscopy, under local anaesthesia. Sterilization may be performed immediately
      following pregnancy, or as an interval operation. The effectiveness of female
      sterilization is high, with failure rates of about 1-2 per 1000 procedures.
      Immediate complications are few and minor, while there appear to be no serious,
      long-term adverse effects. It is possible that there is a protective effect
      against ovarian cancer. Potential new technologies for female sterilization
      include the use of chemicals, such as quinacrine, for transcervical tubal
      occlusion, and hysteroscopic methods. Male sterilization is more simple and can
      readily be performed under local anaesthesia. A new technique originating in
      China, the no-scalpel technique, has made the procedure even more simple and
      produces fewer complications such as haematoma. It is possible that the direct
      injection of plug-forming material into the vas may render the procedure more
      reversible. Concerns about possible adverse effects of vasectomy on
      cardiovascular diseases and testicular cancer largely have been dispelled, but a
      possible weak association between vasectomy and prostatic cancer continues to be
      studied.

PMID- 8736726
TI  - Contraception for the older woman.
AB  - Contraception presents particular problems for women over the age of 40. Although
      fertility is declining and the risk of pregnancy may be small, the consequences
      of an unplanned pregnancy may be socially devastating and medically ill-advised.
      Menstrual dysfunction and psychosexual difficulties increase with age and may
      exacerbate the side-effects of some methods of contraception. The long-term risks
      of combined hormonal contraception, particularly cardiovascular disease, become
      more pertinent to women whose natural risk of disease increases with age.
      Patterns of sexual activity and contraceptive use change with age. The advantages
      and disadvantages of currently available methods of contraception are difficult
      to quantify, and the choice of method is very much a matter for individual
      concern. The increasing prevalence of HRT may complicate matters for some women
      who are unsure for how long to continue using contraception. Contraceptives of
      the future may be designed to improve the reproductive health of all women,
      particularly those approaching the menopause.

PMID- 8736727
TI  - Sexual behaviour in young people.

PMID- 8736728
TI  - Cytarabine release from alpha, beta-poly (N-hydroxyethyl)-DL-aspartamide matrices
      cross-linked through gamma-radiation.
AB  - alpha, beta-Poly (N-hydroxyethyl)-DL-aspartamide solutions were cross-linked
      through gamma-radiation and the systems obtained were tested as matrices for drug
      sustained release, using cytarabine as model drug. We performed the
      characterization of the cross-linked polymer, both drug-loaded and unloaded.
      through water swelling measurements, scanning electron microscopy and X-ray
      analysis. Finally, we investigated the in vitro release behaviour of cytarabine.

PMID- 8736729
TI  - Effectiveness of a bioabsorbable conduit in the repair of peripheral nerves.
AB  - A new conduit made with a bioabsorbable copolymer, poly (L-lactide-co-6
      caprolactone), was evaluated in an animal model as a guide for nerve
      regeneration. The conduit had an inner diameter of 1.3 mm and a wall thickness of
      175 microns. Segments of length 1.2 cm were interposed between the proximal and
      distal stumps of transected ischiatic nerves in Wistar rats, bridging a nerve gap
      of 1 cm. All of the procedure was performed under general anaesthesia using
      microsurgical techniques. Controls were performed at 1, 3 and 6 months and it was
      demonstrated that the conduit was still undamaged after 30 d. Progressive signs
      of degradation appeared at 90 and 180 d. Nerve regeneration in the lumen was
      effective as confirmed by histological and electron microscopical investigations.
      These preliminary results emphasize the interesting properties of the conduit
      with regard to the achievement of a neural prosthesis.

PMID- 8736730
TI  - Quantitative assessment of the tissue response to films of hyaluronan
      derivatives.
AB  - The aim of this study was to evaluate the in vivo response following implantation
      into a rat model of three innovative hyaluronan derivatives for clinical use:
      HYAFF 7, HYAFF 11 and HYAFF 11p75 (respectively, the 100% ethyl ester, 100% and
      75% benzyl esters). The tissue reaction evoked by films of these new biomaterials
      implanted into the dorsolumbar musculature of rats was assessed quantitatively
      using a well established technique based upon an image analysis system. The
      number of inflammatory cells present and the patterns of cell distribution around
      the implant up to a distance of 642 microns were examined at different time
      periods after implantation. Since a well-delineated tissue-material interface was
      needed for this type of investigation, it was not possible to apply image
      analysis to sections once dissolution of the implanted materials had begun. Films
      of both the total esters, HYAFF 7 and HYAFF 11, were found to undergo a slow
      dissolution process and, after a month, films of these materials were still
      present at the site of implantation. Differences in response to the two materials
      were observed only during the first two weeks, particularly with respect to
      neutrophil distribution and total cellularity. HYAFF 7 was found to be more
      reactive, with higher numbers of neutrophils near the surface of the implant than
      HYAFF 11. Thereafter, the differences between the two materials were minimal and
      owing mainly to a faster dissolution of HYAFF 7 films. After 3 and 5 months,
      considerable degradation of films of both total esters had occurred. Significant
      quantities of material appeared inside numerous macrophages with an ED1-positive
      phenotype. Only a very thin layer of fibrous connective tissue, indicative of low
      reactivity, was found to surround the site of implantation, separating the
      dissolved material and the phagocytic cells from healthy muscular tissue. ED2
      positive macrophages were primarily confined within the lining connective tissue.
      The partial benzyl ester, HYAFF 11p75, showed a different behaviour. In fact,
      evidence of film dissolution was already present a week after the implantation.
      After two weeks, the implanted films were completely dissolved and numerous ED1
      positive macrophages phagocytosing the material were observed at the site of
      implantation. Therefore, in agreement with previous in vitro studies, which
      showed a greater susceptibility to degradation of hyaluronan derivatives with
      lower percentage of esterification, HYAFF 11p75 underwent resorption faster than
      the corresponding total ester.

PMID- 8736731
TI  - Comparative animal study of three ligament prostheses for the replacement of the
      anterior cruciate and medial collateral ligament.
AB  - Three different ligament prostheses (Leeds-Keio, Gore-Tex and a prototype of
      Aramid) were implanted in sheep knee joints replacing the anterior cruciate
      ligament and the medial collateral ligament. After 1 yr the knees were explanted
      and their biomechanical properties were assessed by a drawer test and tensile
      tests of the implants. Additionally the ligament replacements, the synovial
      membrane and the lymph nodes were inspected histologically. For each type of
      prosthesis partial or total ruptures occurred. None of the operated joints
      regained normal stability and stiffness. Anterior knee stability was best for the
      Gore-Tex treated group and worst for those joints that received a Leeds-Keio
      implant. The stiffness and rupture strength were highest for the Gore-Tex
      prostheses. Histologically the strongest intra-articular inflammatory response
      was observed in the Gore-Tex treated joints. Inside the drill tunnels the
      severest foreign body reaction was found for the Aramid prostheses. Gore-Tex
      fibres often showed good bony integration. Wear particles formed from all
      prostheses and caused small granulomas and mild synovities. The results suggest
      that none of the tested materials represent an ideal solution for ligament
      replacement. Relatively good stability does not guarantee good biocompatibility
      and vice versa. This suggests that ligament prostheses should be applied only in
      salvage cases.

PMID- 8736732
TI  - Appearance of low signal intensity lines in MRI of silicone breast implants.
AB  - Magnetic resonance (MR) images of five explanted mammary prostheses were obtained
      with a 1.5 T GE Signa system using a conventional spin-echo pulse sequence, in
      order to investigate the low-intensity curvilinear lines which may be observed in
      MR images of silicone gel-filled breast implants under pressure from fibrous
      capsules. MR images showed ellipsoid prostheses, often containing multiple low
      intensity curvilinear lines which in some cases presented an appearance very
      similar to that of the linguine sign. Upon opening the fibrous capsules, however,
      all of the prostheses were found to be completely intact demonstrating that the
      appearance of multiple low signal intensity curvilinear lines in MR images of
      silicone gel-filled prostheses is not necessarily a sign of prosthesis rupture.
      The MR image features which are specific to the linguine sign must be more
      precisely defined.

PMID- 8736733
TI  - Evaluation of an artificial dermis full-thickness skin defect model in the rat.
AB  - An artificial dermis product was applied to full-thickness skin defects in rats
      and cell infiltration into the collagen matrix was investigated. Host fibroblasts
      and capillaries infiltrated as far as the upper end of the collagen matrix by day
      14 after application. Determination of glycosaminoglycan levels in the matrix
      showed that hyaluronic acid was generated in a similar amount to that seen in the
      intact skin by day 14. An autologous thin split-thickness skin graft was placed
      onto the artificial dermis simultaneously or several days after its application
      to the defect. The take rate was 100% when a split-thickness skin graft was
      performed on day 14 after application of the artificial dermis. At 6 weeks after
      the skin defect was created, the wound area was 80% of the original area and the
      dermis at the grafted site was as thick as that of normal skin. These results
      suggested that the artificial dermis provides a good matrix for thin split
      thickness skin graft and is useful for the reconstruction of full-thickness skin
      defects. This method is considered to be an alternative to the conventional
      procedure using thick skin grafts or skin flaps.

PMID- 8736734
TI  - Histological evaluation of skin reconstruction using artificial dermis.
AB  - An artificial dermis, composed of a collagen matrix, was applied to a full
      thickness skin defect prepared on the back of rats. Two weeks later, a thin split
      thickness skin autograft was overlaid on the matrix at each recipient site. The
      dermal layer at the recipient sites was 1.02 mm thick with prior application of
      artificial dermis, as compared with the 0.46 mm thickness observed without such
      pretreatment. Histologically, the split-thickness skin graft normally lies with
      no gap on the artificial dermis, which looks like natural dermis. Six days after
      grafting, the epithelial basal cells in the grafts showed an active uptake of
      bromodeoxyuridine (a thymidine analogue), indicating high activity of cell
      proliferation. About 50 and 20% respectively of the artificial dermis remained at
      each recipient site at 12 and 20 weeks after its application (after the skin
      defect). This finding indicates that bovine collagen, which is a constituent of
      the artificial dermis, is gradually replaced by the host tissue.

PMID- 8736735
TI  - Complement activation by 3-mercapto-1,2-propanediol immobilized on gold surfaces.
AB  - Thiol-modified surfaces are chemically well defined and suited for surface
      biological model experiments and biomaterials research. 3-Mercapto-1,2
      propanediol (mercaptoglycerol, MG), immobilized on gold, spontaneously binds
      immunoglobulins from human serum and activates the complement system. The surface
      bound complement factors were detected by ellipsometry-antibody techniques. The
      overall complement activation was subsequently corroborated independently with
      enzyme immunosorbent assay (EIA) and sheep and chicken erythrocyte haemolytic
      complement techniques. EIA experiments indicated elevated levels of C4d, but no
      significant increase of factor Bb was evident in the test serum from the MG
      system. The haemolytic assays show that MG surfaces consume complement factors
      from both pathways. Ellipsometry revealed that immunoglobulin G (IgG) and
      complement factor 1q (C1q) are transiently antibody detectable on MG after
      exposure to whole serum by the use of antibody techniques. Complement factor 3
      (C3), C2, C4 and properdin could be detected on the surface, but not factors H
      and B. The total adsorbed mass and particularly C3 antibody deposition were
      suppressed by using EGTA-Mg2+ serum. The results suggest that MG surfaces
      initially activate complement via the classical pathway. Other IgG binding
      surfaces also appear to behave in a similar manner.

PMID- 8736736
TI  - Periosteal and endosteal reaction to reaming and nailing: the possible role of
      revascularization on the endosteal anchorage of cementless stems.
AB  - The reaction of bone to titanium implants of different shapes inserted in the
      rabbit tibia was investigated with histological and perfusion techniques to
      determine the pattern of vessel distribution. The experimental implants included
      full cylindrical rods, hollow rods with holes on the surface and wire mesh rods.
      In the implanted bones the rods were found to fill a large area of the medullary
      canal; however, owing to the discrepancy between the shape of the diaphysis and
      the implant, the endosteal contact was never complete. In an early phase,
      reactive bone filled the gap between the endosteal and the implant surface; in
      hollow and wire mesh rods bone had grown inside through the lateral holes or
      loops of the mesh. Revascularization took place together with remodelling of the
      endosteal, primary bone to mature lamellar. In full implants a reticle of newly
      formed vessels developed around the rods; in hollow and wire mesh implants
      vessels had grown inside the implant itself and the endosteal surface had a more
      regular profile than in full rods. Wire mesh plugs prevented formation of a
      peripheral medullary space and showed no encapsulation; wires in contact with or
      in proximity to the endosteal surface were incorporated by lamellar systems with
      strong connections with the original cortical bone.

PMID- 8736737
TI  - Direct bone formation on sand-blasted titanium implants: an experimental study.
AB  - Surface modifications of an implant have been demonstrated to be important in
      influencing the tissue reactions around the implant. Recently, osteoblasts have
      been shown to be capable of laying down a mineralized matrix in direct contact
      with the titanium surface. The aim of the present study was to analyse the early
      bone responses to titanium implants with an aluminium dioxide sand-blasted
      surface. Microscopical analysis showed that in the first week it was possible to
      observe the presence of mineralized bone in direct contact with the metal
      surface, while in other portions of the interface, osteoblasts were seen at the
      implant surface. These results were confirmed in the 2 and 4 wk observations. Our
      results could help to explain the increased removal torque forces reported in the
      literature concerning sand-blasted implants.

PMID- 8736738
TI  - In vitro investigation of fluoride ion release from four resin-modified glass
      polyalkenoate cements.
AB  - Conventional glass ionomer cements are known to release fluoride ions to the
      surroundings. Recently, resin-modified glass ionomer cements have been produced.
      These have differing chemical formulations and this may affect their ability to
      release fluoride ions. The study evaluates both the fluoride release and
      compressive strength of one conventional and four resin-modified glass ionomer
      cements with respect to time. The results showed that the formulation of the
      resin-modified materials influenced the fluoride release. One resin-modified
      glass ionomer (PhotacFil) released more fluoride than all other materials, while
      Vitremer, Fuji II LC and Chemfil Superior release similar amounts. Variglass had
      a very much smaller elution of fluoride ions. This suggests that there is
      considerable variation in fluoride release between materials of similar generic
      origin. The compressive strength of these materials was not affected with time.

PMID- 8736739
TI  - Development of a model for assessment of biomaterial encrustation in the upper
      urinary tract.
AB  - A need exists for ureteral stent materials capable of preventing or reducing
      encrustation. The aim of this study, therefore, was to develop an in vitro model
      producing biomaterial encrustation similar to that on stents in vivo. Three
      models were designed and evaluated. Polyurethane stent sections were immersed in
      human urine (37 degrees C, 5% CO2): (1) with and (2) without crushed human kidney
      stone and (3) in an artificial urine (37 degrees C, 5% CO2). Encrustation of
      similar composition, as determined by infrared spectroscopy, X-ray diffraction
      and energy dispersive X-ray analysis, formed on stent materials in vivo, in
      artificial urine and in human urine with crushed kidney stone. Magnesium ammonium
      phosphate (struvite) and calcium phosphate (hydroxyapatite) predominated in all
      encrustations. The reproducibility and ease of use of the artificial urine model
      provided optimum encrustation assessment of materials presently used in ureteral
      stents and evaluation of novel biomaterials.

PMID- 8736740
TI  - Alginate polycation microcapsules. I. Interaction between alginate and
      polycation.
AB  - The interactions between alginate and polycations have been studied by using
      different labelling techniques. Binding of poly-L-lysine (PLL) to alginate in the
      gel state is mainly governed by the amount of dissociable negative charges on the
      bead surface. PLL was found to bind more rapidly to gel beads made from alginate
      with a high content of mannuronic acid. The binding was enhanced by increasing
      the alginate concentration on the surface by making inhomogeneous beads. When the
      capsules were stored in the presence of cations with high affinity for alginate
      (Ca2+, Sr2+), PLL was washed off. Less PLL is bound to strontium alginate than to
      calcium alginate beads. Two mechanisms appear to be responsible for the binding
      of sodium alginate to alginate PLL capsules (coating): (i) an electrostatic
      interaction between the soluble coating material and excess positive charges on
      PLL on the surface; (ii) the formation of a calcium alginate gel on the surface
      owing to leaching of calcium ions from the core. The stability and efficiency of
      the coating as a function of molecular size and sequential structure of the
      coating polymer have also been investigated.

PMID- 8736741
TI  - Role of leucocytes in coagulation induced by artificial surfaces: investigation
      of expression of Mac-1, granulocyte elastase release and leucocyte adhesion on
      modified polyurethanes.
AB  - Thrombus formation on artificial surfaces can be viewed as the sequential and
      concomitant involvement of protein adsorption, platelet reactions, activation of
      the coagulation system, participation of complement, fibrinolytic and kallikrein
      kinin systems, and the interaction of cellular elements. This study examines the
      activation of leucocytes on a series of well-characterized polyurethanes with
      different ionic groups [sulphonate groups (negatively charged); quaterinary amine
      groups (positively charged)], in terms of adhesion, degranulation and cell
      surface integrin receptor expression. Leucocyte adhesion was monitored with
      radiolabelled neutrophils and scanning electron microscopy (SEM), degranulation
      by measurement of human neutrophil elastase using an indirect enzyme-linked
      immunosorbent assay and cell surface expression of the integrin receptor Mac-1,
      using fluorescent-activated cell sorting (FACS). Our results indicate a trend
      towards enhanced adhesion and degranulation with respect to the negatively
      charged polyurethane. Similar results were observed with respect to the integrin
      Mac-1 from recovered adherent cells. The findings of enhanced adhesion and
      spreading, Mac-1 up-regulation and granulocyte elastase release from the
      negatively charged sulphonated polyurethane indicate the potential of leucocytes
      to contribute towards thrombus formation on such surfaces.

PMID- 8736742
TI  - Encapsulation of artificial tissues in polyelectrolyte complexes: preliminary
      studies.
AB  - The in vitro engineering of vital tissues from isolated cells requires primarily
      the synthesis of a new intercellular matrix. Structural components of the
      extracellular matrix are large molecules such as collagens and proteoglycans. To
      retain and accumulate new matrix molecules within three-dimensional cell
      cultures, chondrocyte-polymer constructs were encapsulated in polyelectrolyte
      complex membranes. Further, these membranes might also be relevant for other
      applications where cells or tissues have to be isolated from their environment by
      semipermeable structures.

PMID- 8736743
TI  - Surgery by numbers?

PMID- 8736744
TI  - Maxillectomy--to reconstruct or obturate? Results of a UK survey of oral and
      maxillofacial surgeons.
AB  - Post-maxillectomy defects may be restored either by surgical reconstruction or by
      prostheses and there is continuing controversy about the most appropriate method
      of rehabilitation in any particular case. A questionnaire was designed to assess
      the current practices of oral and maxillofacial surgeons in the UK after
      resection of the maxilla for malignant disease. Maxillectomies were carried out
      by 83% of surgeons; most surgeons do 1-5 cases a year; 38% of surgeons do
      reconstruct surgically, but only in 10% of cases. Only 65% of surgeons have
      access to the services of a restorative dentist; this did influence 19% of
      surgeons' decision about whether to reconstruct surgically or restore by
      prosthetic means.

PMID- 8736745
TI  - An experimental study of lingual nerve repair using epineurial sutures or
      entubulation.
AB  - The recovery of the mechanosensitive afferent fibres in the lingual branch of the
      trigeminal nerve has been studied using electrophysiological techniques in cats,
      after two methods of nerve repair. After nerve section the lingual nerve was
      repaired by either epineurial sutures or by entubulation. 12 weeks after either
      method of repair the properties of the regenerated fibres were significantly
      different from normal, but following repair with epineurial suture they were
      closer to normal than after repair by entubulation. After entubulation the fibres
      had a greater reduction in conduction velocity, a greater increase in force
      threshold, and the adaptation times were faster. The results suggest that
      epineurial suture should be preferred clinically.

PMID- 8736746
TI  - Self-reinforced polyglycolic acid membrane: a bioresorbable material for orbital
      floor repair. Initial clinical report.
AB  - A self-reinforced polyglycolic acid membrane has been used successfully to repair
      15 orbital floor fractures in 12 consecutive patients. As polyglycolic acid is
      absorbable it does not cause the complications of long-term infection and
      migration associated with non-absorbable bioinert alloplastic repair materials.

PMID- 8736747
TI  - In vitro fracture fixation: adhesive systems compared with a conventional
      technique.
AB  - To find out whether adhesive techniques could have a role in bone fixation in
      selected cases an in vitro comparison between the current 'Champy' miniplate
      system and bonded stainless steel was undertaken using cyanoacrylate or dental
      composite cement. 33 bovine ribs were sectioned to simulate fracture separation,
      divided randomly into three groups, and immobilised by one of the three
      treatments. Distraction across the 'fracture' was produced using a universal
      testing apparatus, and forces at failure were recorded in Newtons (N). Image
      analysis enabled the contact area of the adhesive to be determined in mm2, so the
      bond strength in N/mm2 was derived. The Champy system failed at a significantly
      greater force (N) than the adhesives (p = 0.000). There was no significant
      difference in bond strength between either of the adhesive systems tested.

PMID- 8736748
TI  - Professional attitudes to requests for secondary facial reconstruction in
      patients who have attempted suicide.
AB  - Two patients sustained multiple facial fractures after a suicide attempt. After a
      period of convalescence, both wished to undergo secondary reconstructive surgery
      to improve the cosmetic appearance and function. On the ward, patients induced
      strong emotional reactions in medical staff and nurses. It should be realised
      that in most cases suicide attempts are not fatal. It is essential that a
      psychiatrist is consulted who establishes a psychiatric diagnosis and has an
      active role in further treatment. What may interfere with the indications for
      operation is countertransference from the surgeon to the patient who consciously
      injured himself. Five types of countertransference hatred are distinguished and
      described; repression of countertransference, projection of countertransference,
      reaction formation, reversion, and distortion or denial of reality. Failure to
      recognise this mechanism will result in undertreatment of these patients. A good
      professional understanding between the consultation liaison psychiatrists and the
      surgeons may facilitate a positive outcome of consultations in this area.

PMID- 8736749
TI  - Screw fixation following bilateral sagittal ramus osteotomy for mandibular
      advancement--complications in 700 consecutive cases.
AB  - The use of transbuccal positional screws for stabilisation of bony segments
      following bilateral sagittal split osteotomy for mandibular advancement was
      assessed in 700 consecutive cases. In 19 patients (2.7% of cases) screw fixation
      was not used as the method of fixation. Screw removal was performed in 20
      patients (2.8% of cases), in 15 cases due to infection and 5 cases for diverse
      reasons. The incidence of inferior alveolar nerve damage was increased when
      compared to a group of patients managed with intermaxillary fixation following
      advancement BSSO treated in the same unit. In 4 patients (0.6%) a lingual nerve
      dysaesthesia occurred. Screw loosening in the first postoperative week occurred
      in 4 patients and in 3 of these re-operation was necessary. Extra oral scar
      formation did not give rise to any significant problems.

PMID- 8736750
TI  - The presence of the antilingula and its relationship to the true lingula.
AB  - 20 cadaver mandibles were studied for the presence of an antilingula and its
      relationship to the true lingula and mandibular foramen. Three independent
      observers evaluated the mandibles for the presence of an antilingula. It could be
      identified on all 40 sides. On 9 of the sides, there was complete concordance on
      the position of the antilingula between the three observers. On the other 31
      sides, however, there was a variation between observers of up to 11 mm. In only
      43% of the cases was the antilingula within 5 mm of the true lingula. In most
      cases, the true lingula was postero-inferior to the antilingula. There was a
      negative horizontal and positive vertical correlation between the position of the
      antilingula on one side and its position on the contralateral side.

PMID- 8736751
TI  - Traumatic bilateral hypoglossal nerve palsy.
AB  - A case of bilateral hypoglossal nerve palsy following a road traffic accident is
      reported. The possible aetiology is discussed.

PMID- 8736752
TI  - Avoiding artefacts in oral biopsies: the punch biopsy versus the incisional
      biopsy.
AB  - Fifty oral biopsy specimens were removed, 24 with a punch and 26 by conventional
      incision with a scalpel. All specimens were routinely processed in the
      histopathology laboratory and examined for artefacts. Significantly fewer
      artefacts were found in the punch biopsy group compared to the incisional biopsy
      group. Access for the punch was not found to be a problem.

PMID- 8736753
TI  - Actinomycosis--an unusual presentation.
AB  - We report an unusual presentation of orofacial actinomycosis mimicking the
      clinical appearance of a minor salivary gland tumour of the upper lip.
      Histological examination confirmed the diagnosis and we think that the lesion was
      caused by infection of a mucocele of the upper lip by Actinomyces israelii, an
      oral commensal.

PMID- 8736754
TI  - Treatment of over-reduction of the nose and subsequent deformities.
AB  - Failures after rhinoplasty are the result of both technical mistakes and of
      errors of judgement. One of the most common errors is resection of too much
      tissue from the components of the nose: the dorsum, alar cartilages, or septum.
      Such deformities may have both cosmetic and functional effects. The defects that
      most commonly make a nose look unnatural are: a shallow nasofrontal angle, a nose
      that has been shortened too much, an over-reduced dorsum which emphasises a
      parrot's beak deformity, and a round nasal tip with a short interdomal length
      that lacks definition. The purpose of this paper is to describe the most common
      deformities associated with excessive resection of the nose, and to suggest the
      appropriate procedures for correcting the defects. Grafting is usually necessary.
      We will deal first with deformities of the dorsum and septum and then of the
      nasal base, but it must be borne in mind that a defect in one area is likely to
      affect the other areas because they are interrelated-for example, over-resection
      of the dorsum may also effect the tip of the nose. In addition, not all
      deformities are the result of excessive reduction; some may result from
      inadequate resection.

PMID- 8736755
TI  - Third molar surgery: an audit of the indications for surgery, postoperative
      complaints and patient satisfaction.

PMID- 8736756
TI  - Management of soft tissue facial wounds.

PMID- 8736757
TI  - Central giant cell granulomas of the jaws.

PMID- 8736758
TI  - Tyrosine phosphorylation: past, present and future.

PMID- 8736759
TI  - Biomembranes, ion channels and new biomaterials.

PMID- 8736760
TI  - Fishing in the stream of diabetes: from measuring insulin to the control of fetal
      organogenesis.

PMID- 8736761
TI  - Regulation of promoters by two transcription activators: evidence for a
      'simultaneous touching' model.

PMID- 8736762
TI  - Basic helix-loop-helix transcription factors and the cross-regulation of sulphate
      and phosphate metabolism in yeast.

PMID- 8736763
TI  - Regulation of gene expression by ambient pH in Aspergillus: genes expressed at
      acid pH.

PMID- 8736764
TI  - Metabolic regulation of hepatic gene expression.

PMID- 8736765
TI  - Regulation of insulin gene transcription by nutrients.

PMID- 8736766
TI  - Regulation of lipogenic enzyme expression by glucose in liver and adipose tissue:
      is glucose 6-phosphate the signalling metabolite?

PMID- 8736767
TI  - Regulation of gene expression by insulin: analysis in single living cells.

PMID- 8736768
TI  - Regulation of selenoprotein gene expression and thyroid hormone metabolism.

PMID- 8736769
TI  - Nutrient regulation of intestinal sugar-transporter expression.

PMID- 8736770
TI  - Functional interpretation of the organization of mammalian adipose tissue: its
      relationship to the immune system.

PMID- 8736771
TI  - Early adipocyte differentiation.

PMID- 8736772
TI  - Uncoupling protein in brown adipose tissue: molecular differentiation of the
      adipose tissues.

PMID- 8736773
TI  - Adrenergic regulation of brown adipocyte differentiation.

PMID- 8736774
TI  - Beta 3-adrenoceptors and the regulation of metabolism in adipose tissues.

PMID- 8736775
TI  - Immunological manipulation of adiposity.

PMID- 8736776
TI  - Nutritional influences on human adipose-tissue metabolism.

PMID- 8736777
TI  - Oxygen processing in photosynthesis.

PMID- 8736778
TI  - Peroxisomes as a source of superoxide and hydrogen peroxide in stressed plants.

PMID- 8736779
TI  - The origin of the oxidative burst in plants.

PMID- 8736780
TI  - Free radicals and other paramagnetic ions in interactions between fungal
      pathogens and potato tubers.

PMID- 8736781
TI  - Superoxide generation in relation to dehydration and rehydration.

PMID- 8736782
TI  - Free radicals and metabolism associated with the acquisition and loss of
      desiccation tolerance in developing seeds.

PMID- 8736783
TI  - Plant defence systems and ozone.

PMID- 8736784
TI  - Gaseous pollutants and plant defence mechanisms.

PMID- 8736785
TI  - Manipulation of glutathione metabolism in transgenic plants.
AB  - There is clear potential for the genetic manipulation of key enzymes involved in
      stress metabolism in transgenic plants. However, the data emerging so far from
      such experiments are equivocal. The detailed analysis of stress responses in
      progeny of primary transgenics, coupled with comparisons with control transgenic
      plants that do not contain the GR transgene, allows us to take into account the
      possible variation in response to stress associated with regeneration of plants
      from tissue culture. The picture that is now beginning to emerge with respect to
      the role of GR in stress protection is that, although there are clearly benefits
      to be had from overexpression of the enzymes, there is no direct correlation
      between enzyme levels and stress tolerance. It may be that overexpression of the
      cytosolic isoform (gor2) will prove to be of greater benefit. Furthermore, the
      types of stresses to which transgenic plants have been exposed in order to assess
      the consequences of oxidative stress tolerance cannot reproduce those that will
      experienced in field conditions. Only when plants with higher GR levels and
      increased glutathione synthesis capacity are grown in field trials will it be
      possible to make a full assessment of the benefits of engineering plants with
      altered glutathione metabolism.

PMID- 8736786
TI  - Oxidative stress and responses in Arabidopsis thaliana and Oryza sativa subjected
      to chilling and salinity stress.

PMID- 8736787
TI  - Ascorbate metabolism in relation to oxidative stress.

PMID- 8736788
TI  - Cytosolic calcium and oxidative plant stress.

PMID- 8736789
TI  - Free radical formation in non-photosynthetic plant tissue--an overview.

PMID- 8736790
TI  - Understanding the heterogeneity of the limb-girdle muscular dystrophies.

PMID- 8736791
TI  - Structure-function relationships in dystrophin and utrophin.

PMID- 8736792
TI  - Costameric distribution of beta-dystroglycan (43 kDa dystrophin-associated
      glycoprotein) in normal and dystrophin-deficient human skeletal muscle.

PMID- 8736793
TI  - Skeletal muscle development and the role of the myogenic regulatory factors.

PMID- 8736794
TI  - Is myotonic dystrophy a single-gene disorder?

PMID- 8736795
TI  - Gene transfer to muscle.

PMID- 8736796
TI  - mRNA targeting: signals in the 3'-untranslated sequences for sorting of some
      mRNAs.

PMID- 8736797
TI  - Targeting proteins to mitochondria: is there a role for mRNA localization?

PMID- 8736798
TI  - Localization signals in proteins internalized from the cell surface.

PMID- 8736799
TI  - Intracellular targeting of secretory proteins in neuroendocrine cells.

PMID- 8736800
TI  - Trafficking, targeting and translocation of the insulin-responsive glucose
      transporter, GLUT4, in adipocytes.

PMID- 8736801
TI  - Intracellular transport of the low-density lipoprotein receptor.

PMID- 8736802
TI  - Hijacking host cell signal transduction mechanisms during infection with
      enteropathogenic Escherichia coli.

PMID- 8736803
TI  - The central regulation of energy homeostasis: roles of neuropeptide Y and other
      brain peptides.

PMID- 8736804
TI  - Hormones and the ob gene product (leptin) in the control of energy balance.

PMID- 8736805
TI  - Pancreatic B-cells as mediators of metabolic effects of regulatory peptides.

PMID- 8736806
TI  - Metabolic actions of neuropeptide Y and their relevance to obesity.

PMID- 8736807
TI  - Central glucagon-like peptide-I in the control of feeding.

PMID- 8736808
TI  - The metabolic role of GIP: physiology and pathology.

PMID- 8736809
TI  - Regulatory peptides in the control of metabolism during starvation and exercise.

PMID- 8736810
TI  - Islet amyloid polypeptide: actions and role in the pathogenesis of diabetes.
AB  - IAPP has been postulated to have a role as a modulating factor in glucose
      homoeostasis and to be involved in the pathophysiology of diabetes. However, the
      normal physiological functions of the peptide remain obscure: exogenous IAPP acts
      on many experimental systems to modulate nutrient supply and metabolism but there
      is no evidence to suggest that circulating IAPP has an aetiological role in the
      onset of Type-2 diabetes. Amyloid deposits formed from polymerized IAPP
      progressively accumulate in the islets of Type-2 diabetic patients. These
      insoluble deposits do not precipitate the onset of hyperglycaemia in Type-2
      diabetes, but progressive accumulation of amyloid is associated with islet cell
      destruction and decreased islet function in the later stages of the disease.
      Although the causative factors of formation of the first IAPP fibril are unknown,
      continued high levels of insulin and IAPP secretion as a result of nutrient
      stimulation or insulin resistance will promote binding to preformed fibrils and
      extension of the deposits. It is important that methods to identify patients
      susceptible to amyloid deposition are developed and therapeutic agents are
      produced that can reduce or prevent polymerizatin of IAPP to form amyloid and
      minimize severe deterioration of islet function in Type-2 diabetes.

PMID- 8736811
TI  - Lipoproteins in non-insulin dependent diabetes mellitus (NIDDM).

PMID- 8736812
TI  - Alterations in plasma lipoprotein concentrations in patients with peripheral
      vascular disease.

PMID- 8736813
TI  - A brain receptor for a subfraction of high density lipoprotein containing
      apolipoprotein E.

PMID- 8736814
TI  - Ob (obese) gene expression in white adipose tissue of obese Zucker (fa/fa) rats.

PMID- 8736815
TI  - Expression of the ob (obese) gene during lactation in mice.

PMID- 8736816
TI  - Lack of effect of different dietary saturated fatty acids on adipose tissue
      deposition in the rat.

PMID- 8736817
TI  - Metallothionein gene expression in brown adipose tissue.

PMID- 8736818
TI  - The effect of feeding diets with different n-6/n-3 fatty acids ratios on adipose
      tissue of deposition in the rat.

PMID- 8736819
TI  - Adipose tissue development in the chick embryo.

PMID- 8736820
TI  - Insulin signal transduction in adipocytes from lactating sheep.

PMID- 8736821
TI  - Treatment of pluripotential C3H 10T1/2 fibroblasts with bone morphogenetic
      protein-4 induces adipocyte commitment.

PMID- 8736822
TI  - Preadipocyte factor-1 expression in the mouse embryo and placenta.

PMID- 8736823
TI  - Preferential mobilisation of docosahexaenoic acid from adipose tissue
      triacylglycerol of the chick embryo.

PMID- 8736824
TI  - The characterisation of expression of three murine peroxisome proliferator
      activated receptor genes.

PMID- 8736826
TI  - Effect of insulin on glucose transport in adipose tissue in lactation.

PMID- 8736825
TI  - Platelet membrane glycoprotein IV (CD36) is involved in arachidonic acid induced
      platelet aggregation.

PMID- 8736827
TI  - Lipoprotein lipase mRNA levels in adipose tissue in lactation.

PMID- 8736828
TI  - A novel method for the rapid separation of human plasma lipoproteins using self
      generating gradients of Iodixanol.

PMID- 8736830
TI  - Apolipoprotein CII & CIII in non-insulin dependent diabetic patients.

PMID- 8736829
TI  - Carotenoid profiles of human plasma lipoproteins.

PMID- 8736831
TI  - Effect of flavonoids on arachidonic acid metabolism and prostacyclin (PGI2)
      formation in human vascular endothelial cells.

PMID- 8736832
TI  - Effect of heavy metals on lipids from the freshwater alga Selenastrum
      capricornutum.

PMID- 8736833
TI  - The effect of dietary lipid manipulation on the uptake of [3H]-triolein by
      tissues of the rat.

PMID- 8736834
TI  - Regulation of glutathione peroxidase (GSHPx) activity in human vascular
      endothelial cells by fatty acids.

PMID- 8736835
TI  - Retention of orotic acid effect on very low density lipoproteins secretion in
      cultured hepatocytes.

PMID- 8736836
TI  - Oxysterols and human endothelial cell function.

PMID- 8736837
TI  - Reaction of proteins with vehicle exhaust soot.

PMID- 8736838
TI  - Interactive effects of dietary cholesterol and saturated fat on low density
      lipoprotein cholesterol.

PMID- 8736839
TI  - The relationship between the fatty acid composition of the lipids of the yolk and
      the brain of the duck embryo.

PMID- 8736840
TI  - Tissue-specific development of antioxidant systems during avian embryogenesis.

PMID- 8736841
TI  - Interactions between lipid and insulin in the regulation of apolipoprotein B
      secretion.

PMID- 8736842
TI  - Evidence that both the acyl-CoA- and malonyl-CoA binding sites of mitochondrial
      overt carnitine palmitoyltransferase (CPT I) are exposed on the cytosolic face of
      the outer membrane.

PMID- 8736843
TI  - The addition of a glycosyl-phosphatidylinositol-anchor to a soluble form of
      neutral endopeptidase re-establishes its apical targeting in LLC-PK1 cells.

PMID- 8736844
TI  - Role of the glycosyl-phosphatidylinositol anchor in membrane protein sorting in
      Madin-Darby canine kidney cells.

PMID- 8736845
TI  - Enrichment of specific mRNAs in cytoskeletal-bound and membrane-bound polysomes
      in Chinese hamster ovary cells.

PMID- 8736846
TI  - Localisation of beta-globin reporter sequences to the perinuclear cytoplasm by
      myosin heavy chain and vimentin 3'untranslated regions.

PMID- 8736847
TI  - Distribution of glutathione peroxidase mRNAs between free and cytoskeletal-bound
      polysomes in H4 hepatoma cells.

PMID- 8736849
TI  - Effect of oral supplementation with micronutrient antioxidants on trans fatty
      acid content of lipoproteins in healthy humans.

PMID- 8736848
TI  - Isolation and characterization of two intracellular GLUT4 glucose transporter
      pools in rat skeletal muscle.

PMID- 8736850
TI  - Effects of 7B2 on the maturation of pro-hormone convertase 2 (PC2) in vitro.

PMID- 8736851
TI  - Mutations in the pro-peptide of PC2 prevent transit through the secretory
      pathway.

PMID- 8736852
TI  - The antioxidant activity of heparins.

PMID- 8736853
TI  - Superoxide generation in plant peroxisomal membranes: characterization of redox
      proteins involved.

PMID- 8736854
TI  - Purification and characterization of peroxisomal and mitochondrial Mn-superoxide
      dismutases from watermelon cotyledons.

PMID- 8736855
TI  - Modulation of human platelet function by food flavonoids.

PMID- 8736856
TI  - Active oxygen metabolism in the senescence of pea leaves: ascorbate and
      glutathione contents in different cell compartments.

PMID- 8736857
TI  - Elicitor-induced generation of active oxygen in suspension cultures of
      Arabidopsis thaliana.

PMID- 8736858
TI  - Stress tolerance of transgenic Nicotiana tabacum with enhanced activities of
      glutathione reductase and superoxide dismutase.

PMID- 8736859
TI  - alpha-Tocopherol binding activity of human red blood cells: implications in
      nutritional assessment of vitamin E status.

PMID- 8736861
TI  - Similarity and dissimilarity in aspects of the binding to heparin of Ca2+ and
      Zn2+ as revealed by potentiometric titration.

PMID- 8736860
TI  - alpha-Tocopherol-binding protein in the cytosol of the human placenta.

PMID- 8736862
TI  - The binding of platinum (II) to heparin.

PMID- 8736863
TI  - Blast disease of rice in regard to active oxygen.

PMID- 8736864
TI  - The expression of plasminogen activators and their inhibitors in cultured human
      retinal capillary endothelial cells.

PMID- 8736865
TI  - Characterisation of a monoclonal antibody which recognises the enzyme chitinase
      from Lepeophtheirus salmonis.

PMID- 8736866
TI  - Novel approaches to the purification and identification of cytochrome P450
      enzymes in the equine.

PMID- 8736867
TI  - Human diadenosine 5',5"'-P1,P4-tetraphosphate pyrophosphohydrolase (Ap4A
      hydrolase) possesses a MutT motif.

PMID- 8736868
TI  - Characterisation of Sxa2, a carboxypeptidase involved in pheromone recovery in
      fission yeast.

PMID- 8736869
TI  - Maturation of Krp1, an endopeptidase from the fission yeast Schizosaccharomyces
      pombe.

PMID- 8736870
TI  - The effect of starvation and ethanol on c-myc messenger RNA expression in the
      heart.

PMID- 8736871
TI  - The effect of novel detergents on hepatic microsomal glucose-6-phosphatase
      activity.

PMID- 8736872
TI  - Anabolic effects of a range of beta 2-adrenoceptor agonists in a clonal G8.P8
      cell line.

PMID- 8736873
TI  - Clenbuterol is not an agonist of Na+ dependent creatine transport.

PMID- 8736874
TI  - Glucose-mediated regulation of GLUT-1 and GLUT-3 mRNA in human retinal
      endothelial cells.

PMID- 8736875
TI  - The effect of transforming growth factor beta 1 on the function of HepG2 hepatoma
      cells.

PMID- 8736876
TI  - The effect of oxygen concentration on the function of human Hep G2 hepatoma cells
      and primary cultures of rat hepatocytes.

PMID- 8736877
TI  - Regulation of the activities of citrate synthase isoenzymes from Pseudomonas
      aeruginosa PAC 514.

PMID- 8736878
TI  - Metallothionein isoform analysis by liquid chromatography-electrospray ionisation
      mass spectrometry.

PMID- 8736879
TI  - Effect of extracellular matrix and growth arrest on the alkaline phosphatase
      activity of F9 embryonal carcinoma cells.

PMID- 8736880
TI  - Effect of plane of nutrition and growth hormone treatment on insulin receptor
      gene expression and kinase activity of sheep muscle and adipose tissue.

PMID- 8736881
TI  - Regulation of acetyl CoA carboxylase gene expression in adipose tissue from
      lactating sheep.

PMID- 8736882
TI  - A cell culture model to study regulation of selenoprotein gene expression of
      selenium.

PMID- 8736883
TI  - A competitive prehybridisation assay for validating the specificity of
      oligonucleotide probes: application for analysis of rat metallothionein -1 and -2
      mRNA.

PMID- 8736884
TI  - Uptake and bioavailability of dietary polyamines.

PMID- 8736885
TI  - Melatonin regulated gene expression in pars tuberalis cells of the ovine
      pituitary investigated by differential display.

PMID- 8736886
TI  - Glucose mediated regulation of transforming growth factor beta in human retinal
      endothelial cells.

PMID- 8736887
TI  - Polyamine acetylation and apoptosis.

PMID- 8736888
TI  - Hydrogen peroxide induces the catabolism of polyamines in human breast cancer
      cells.

PMID- 8736889
TI  - Effect of the thiazolidinedione antihyperglycaemic agent BRL 49653 on liver fatty
      acid binding protein gene expression.

PMID- 8736890
TI  - The inheritance of a novel mutation in glycogen storage disease type 1a.

PMID- 8736891
TI  - Regulation of the fatty acid synthase promoter by retinoic acid.

PMID- 8736892
TI  - Reduced insulin sensitivity of isolated skeletal muscle but enhanced lipogenic
      capacity of adipocytes in both spontaneously hypertensive and Wistar Kyoto rats.

PMID- 8736893
TI  - Teratogenic potential of free-radicals and hexokinase isoenzymes in the
      postimplantational "diabetic" rat conceptus.

PMID- 8736894
TI  - Relationships between hypothalamic neuropeptide Y and food intake in the
      lactating rat.

PMID- 8736895
TI  - Effect of zinc on metallothionein content of CHO cells transfected with
      metallothionein gene under the control of a non-inducible promoter.

PMID- 8736896
TI  - GLUT1 to 5 & SGLT1 expression in thyroid-hormone-treated Caco-2 cells.

PMID- 8736897
TI  - IUF1, a nutrient responsive transcription factor in the pancreatic beta-cells.

PMID- 8736898
TI  - Mapping nutrient regulatory sequences in the insulin gene.

PMID- 8736899
TI  - Endoplasmic reticulum enzyme systems in developing human fetal trachea.

PMID- 8736900
TI  - Glucose-6-phosphatase in rat pancreas.

PMID- 8736901
TI  - Glucose-6-phosphatase in developing human oesophagus.

PMID- 8736902
TI  - Altered glycogen synthesis associated with changes in cell volume of rat skeletal
      muscle myotubes in primary culture.

PMID- 8736903
TI  - Inhibition of HIV-1 replication by uridine-3'-spiroxirane, a new type of reverse
      transcriptase inhibitor.

PMID- 8736904
TI  - Studies on the Escherichia coli melAB promoter.

PMID- 8736905
TI  - Mechanism of peptide transport in ruminant intestinal brush-border membrane.

PMID- 8736906
TI  - Factors and molecular mechanisms involved in the regulation of chicken colonic
      luminal membrane Na(+)-linked transport systems.

PMID- 8736907
TI  - Asymmetric distribution of the plasma membrane fatty acid-binding protein
      (FABPpm) in the human placenta.

PMID- 8736908
TI  - Glucose catabolism induces the L-type pyruvate kinase gene (125a).

PMID- 8736909
TI  - Can HPV16 detection rationalise the management of women with mild or moderate
      dyskaryosis?

PMID- 8736911
TI  - Characterisation of the expression of Wnt-1 and Wnt-5A related genes from
      Lepeophtheirus salmonis during embryonic development.

PMID- 8736910
TI  - Expression of a DNA binding protein in tumours.

PMID- 8736912
TI  - Identification and expression of antigens from Lepeophtheirus salmonis for use in
      vaccination trials.

PMID- 8736913
TI  - Evaluation of filamentous bacteriophage as immunogens in Atlantic salmon.

PMID- 8736914
TI  - A comparison of different chemiluminescent substrates for the detection of
      endothelial adhesion molecule transcripts.

PMID- 8736915
TI  - The adherence of Streptococcus mutans and streptococcal antigen I/II to a high
      molecular weight human salivary glycoprotein.

PMID- 8736916
TI  - Effect of growth factors on fibroblast migration in a simplified wound healing
      model.

PMID- 8736917
TI  - Induction of stress proteins in human skin keratinocytes by heat, ultraviolet and
      8-methoxypsoralen.

PMID- 8736918
TI  - Analysis of K-ras in the stools of patients with colorectal tumors.

PMID- 8736919
TI  - Altered myosin heavy chain in hearts of ethanol exposed rats.

PMID- 8736920
TI  - The involvement of catecholamines, in hypertension, alcohol and ACE-inhibition.

PMID- 8736921
TI  - Changes in composition and polyamine content in the gastrointestinal tract due to
      pathogenic infection.

PMID- 8736922
TI  - Altered renal intermediary metabolism and the onset of renal dysfunction in the
      streptozotocin diabetic rat.

PMID- 8736923
TI  - Sulphur amino acid derivatives as inhibitors of vitamin B12 dependent methionine
      synthase.

PMID- 8736924
TI  - Experimental D-penicillamine-induced myopathy.

PMID- 8736926
TI  - Glycogen phosphorylase may be activated by AMP-kinase in skeletal muscle.

PMID- 8736925
TI  - Ligand-induced differentiation of glucocorticoid receptor (GR) trans-repression
      and transactivation.

PMID- 8736927
TI  - Purification of GnSAF from human follicular fluid for production of a monoclonal
      antibody.

PMID- 8736928
TI  - Characterization of monoclonal antibodies against arginine vasopressin.

PMID- 8736929
TI  - Thyroid hormones in burn injured children.

PMID- 8736930
TI  - Evidence for distinct dystrophin C-terminal transcripts in rabbit brain.

PMID- 8736931
TI  - Detection of germinal mosaicism in a DMD family.

PMID- 8736932
TI  - Immunogold localization of adhalin, alpha-dystroglycan and laminin in normal and
      dystrophic skeletal muscle.

PMID- 8736933
TI  - Retroviral-mediated gene transfer into murine and human skeletal muscle for the
      correction of dystrophin deficiency.

PMID- 8736934
TI  - Modulation of pre-mRNA splicing in the Duchenne muscular dystrophy gene.

PMID- 8736935
TI  - Adenoviral vectors for gene transfer of full-length human dystrophin cDNAs.

PMID- 8736936
TI  - Cloning and expression of human S-laminin.

PMID- 8736937
TI  - Correction of the dystrophic phenotype by germ-line gene therapy with recombinant
      dystrophin cDNAs in mdx mice.

PMID- 8736938
TI  - Low probability of dystrophin and utrophin coiled coil regions forming dimers.

PMID- 8736939
TI  - The protein defect in congenital muscular dystrophy.

PMID- 8736940
TI  - A search for genes in the facioscapulohumeral muscular dystrophy region.

PMID- 8736941
TI  - A 3.7kb fragment from the myotonic dystrophy protein kinase promoter directs
      neural-specific expression in vivo.

PMID- 8736942
TI  - Changes in adult muscle phenotype in response to disuse and passive stretch.

PMID- 8736943
TI  - Use of synthetic peptides to produce a variety of fibrin antibodies.

PMID- 8736944
TI  - Functional characterisation of the neuropeptide Y receptor mediating feeding in
      the rat.

PMID- 8736945
TI  - Processing of Leu-enkephalin by rat hepatocytes.

PMID- 8736947
TI  - Electrospray ionisation mass spectrometry (ESI/MS) of ceroid lipofuscin protein;
      a model system for the study of F0 inhibitor interactions with mitochondrial
      subunit C.

PMID- 8736946
TI  - Concentrations of gut hormones in control and lactating sheep.

PMID- 8736948
TI  - Electrospray ionisation mass spectrometry (ESI/MS) studies of organotin
      interactions with ceroid lipofuscin protein (subunit C).

PMID- 8736949
TI  - The transmembrane structure of IsK potassium channel.

PMID- 8736950
TI  - Effects of aliphatic alcohols on the ER calcium pumps and InsP3 receptors from
      porcine cerebellum.

PMID- 8736951
TI  - Can phenolic plasticising agents affect testicular development by disturbing
      intracellular calcium homeostasis?

PMID- 8736953
TI  - Characterisation of N-methyl-D-aspartate (NMDA)-induced kindling.

PMID- 8736952
TI  - Actions of the anticonvulsant agent 2-amino-4-phosphonobutyrate on the release of
      [3H]D-aspartate from rat forebrain slices.

PMID- 8736954
TI  - Redox regulation of RNA synthesis in plant mitochondria.

PMID- 8736955
TI  - Molecular modelling of the pore of potassium channels by restraints-directed
      distance geometry.

PMID- 8736956
TI  - Tyrosine dephosphorylation in the gut.

PMID- 8736957
TI  - FTIR spectroscopic analysis of the structure and stability of pig citrate
      synthase.

PMID- 8736958
TI  - Modulation of cell proliferation by fibrin degradation products.

PMID- 8736959
TI  - Evaluation of tumor-associated antigens and total sialic acid levels in effusions
      of malignant and benign origin.

PMID- 8736960
TI  - Serum MCA, CA 125 and CA 19.9 determination in primary breast cancer.

PMID- 8736961
TI  - Lipid mimetics as inhibitors of human platelet phospholipase A2.

PMID- 8736962
TI  - Development of a radioimmunoassay to a fragment of vasostatin II.

PMID- 8736963
TI  - Lipid-helix interactions in membrane receptors.

PMID- 8736964
TI  - Immunohistochemical analysis of p185 in normal and transformed human tissues.

PMID- 8736965
TI  - Immunodominant regions of the extra-cellular domain of the bovine growth hormone
      receptor.

PMID- 8736966
TI  - Faecal calprotectin: non-invasive marker of gastrointestinal inflammation in
      Salmonella infected rats.

PMID- 8736967
TI  - The mechanism of calprotectin's candidastatic activity appears to involve zinc
      chelation.

PMID- 8736968
TI  - Elevated plasma levels of L1L and L1H in CF patients.

PMID- 8736969
TI  - Microbiostatic activity of human plasma and its relation to zinc and iron
      availability.

PMID- 8736970
TI  - Some effects of fluoride on the IgA protease of the oral bacterium Streptococcus
      sanguis.

PMID- 8736971
TI  - Construction of a single-chain Fv from an antibody which catalyses a Diels Alder
      cycloaddition.

PMID- 8736972
TI  - Phage antibodies: new technology to obtain monoclonal antibodies to the multidrug
      resistance gene product P-glycoprotein.

PMID- 8736974
TI  - T cell receptor repertoire in peripheral blood and bronchial biopsies from normal
      and asthmatic subjects.

PMID- 8736973
TI  - Cytokine mRNA profiles of normal and asthmatic peripheral blood cells and
      endobronchial biopsies.

PMID- 8736975
TI  - Kidney and urine enzyme activity in experimental gentamicin nephrotoxicity in the
      Sprague-Dawley rat.

PMID- 8736976
TI  - Muscle protein release following down hill walking.

PMID- 8736977
TI  - HIV-1 virus infected T lymphocytes. The behaviour of purine metabolism.

PMID- 8736978
TI  - Purification and kinetic properties of cardiac calmodulin dependent cyclic
      nucleotide PDE (PDE-I).

PMID- 8736979
TI  - Serum copper and ceruloplasmin concentrations in patients with primary breast
      cancer.

PMID- 8736980
TI  - Glutathione S-transferase of human kidney: are there gender-related quantitative
      differences?

PMID- 8736981
TI  - The accessibility of proteins in protein-SDS complexes.

PMID- 8736983
TI  - Isocyanate inactivation of yeast glutathione reductase & its modulation by
      oxidised glutathione and NADPH.

PMID- 8736982
TI  - The reaction of phosphoglycerate mutase from Schizosaccharomyces pombe with
      diethylpyrocarbonate.

PMID- 8736984
TI  - Glutathione S-transferases in cultured human proximal tubular cells.

PMID- 8736985
TI  - Differential expression of CYP1A1 and CYP1B1 in human breast cancer.

PMID- 8736986
TI  - Cytochrome P450 1B1 expression in human malignant tumours.

PMID- 8736987
TI  - Expression of matrix metalloproteinases in colorectal cancer.

PMID- 8736989
TI  - Inflammatory alpha-1-acid glycoprotein shows an altered reactivity to the lectin
      Concanavalin A.

PMID- 8736988
TI  - Molecular cloning and expression of cDNAs for rat and human kidney cysteine
      conjugate beta-lyase.

PMID- 8736990
TI  - The anti-proliferative effect of alpha-1-acid glycoprotein from HepG2 cell line
      on mononuclear leucocytes.

PMID- 8736991
TI  - Interaction between anionic amino acids and the mammary tissue (Na(+)-glutamate)
      cotransporter.

PMID- 8736992
TI  - The effect of non-steroidal anti-inflammatory drugs on volume-activated amino
      acid transport.

PMID- 8736993
TI  - Mammary tissue protein synthesis is regulated by cell volume.

PMID- 8736994
TI  - Sample handling techniques for analysis of neurokinin A in human saliva.

PMID- 8736995
TI  - Review of neurotransmitters and their role in alcoholism treatment.
AB  - Studies on the genetic basis of addiction indicate that the tendency to develop
      alcoholism is inherited. In addition, alcoholism appears to be associated with a
      specific neurochemical disorder. Research has focused on the mesolimbic system,
      which is associated with the ability to feel pleasure (i.e. hypothalamic control
      centres are related to daily survival activities, and the medial forebrain bundle
      is involved in the positive reinforcement of addictive drugs). Current findings
      support the hypothesis that a neurochemical deficiency causes alcohol-dependent
      individuals to drink. Thus, pharmacotherapy may play an important part in
      treating those who are not helped by psychosocial therapy alone. Future therapies
      may include agents that block, enhance, or normalize neurotransmitter function as
      well as genetically engineered agents that could target a specific cause of
      alcoholism.

PMID- 8736996
TI  - The role of neurotransmitters in alcohol dependence: animal research.
AB  - Animal studies have demonstrated that alcohol changes neurotransmitter
      concentrations in the brain. These changes in levels of dopamine, serotonin,
      gamma-aminobutyric acid (GABA), endogenous opioid peptides, and noradrenaline are
      associated with activation of reward centres in the brain. It is this property of
      alcohol that is believed to be responsible for the reinforcing effect of alcohol
      consumption in rats. One class of neurotransmitters, the endogenous opioid
      peptides, are believed to play an important role in alcohol reinforcement. This
      view is supported by the reduced preference for alcohol consumption found in rats
      given an opiate agonist. The widely distributed inhibitory neurotransmitter GABA
      is also believed to play a fundamental role in mediating the effects of alcohol.
      A better understanding of the mechanisms that support alcohol dependence in
      animals offers hope for the development of pharmacological interventions to block
      these mechanisms, an approach that is now being explored in humans.

PMID- 8736997
TI  - Alcohol reinforcement and neuropharmacological therapeutics.
AB  - The pleasant subjective effects produced by alcohol undoubtedly reinforce
      drinking behaviour. Alcohol positively reinforces or rewards drinking by
      producing a mild euphoria. Alcohol also has anxiolytic effects that negatively
      reinforce drinking. The reinforcing effects of alcohol are mediated by several
      neurochemical systems, with dopamine and serotonin playing major roles in reward
      and the gamma-aminobutyric acid-benzodiazepine receptor system playing a major
      role in negative reinforcement. Research from our laboratory suggests that the
      behavioural effects of alcohol change when blood alcohol levels are changing and
      that these changes correspond to alterations of specific neurochemical systems.
      Behavioural activation and reward effects appear to occur as blood alcohol
      concentrations (BACs) increase. Depressive and aversive effects of alcohol occur
      during the period when BACs decrease. The observed correlation between
      behavioural and neuropharmacological changes and alcohol consumption suggest that
      alcohol produces a unique cascade over time that may provide clues to its long
      sought specific mechanisms of action. In alcohol-dependent individuals, chronic
      exposure to alcohol may alter the function and communication between the liver,
      brain and other vital organ systems involved in hunger and the maintenance of
      nutrition. Under such conditions, the importance of alcohol in the diet may be
      enhanced such that hunger signals in the alcohol-dependent individual motivate
      the consumption of alcohol. Therefore, hunger for alcohol may provide an
      additional source of reinforcement. Endogenous opioid mechanisms may be important
      in this form of alcohol reinforcement.

PMID- 8736998
TI  - Use of serotonin (5-HT) and opiate-based drugs in the pharmacotherapy of alcohol
      dependence: an overview of the preclinical data.
AB  - Numerous neurotransmitter systems [e.g. dopamine, gamma-aminobutyric acid (GABA),
      the endogenous opioids, and serotonin (5-hydroxytryptamine, 5-HT)] are involved
      in the regulation of alcohol consumption. Because 5-HT reuptake inhibitors and
      opioid antagonists modify the activity of neurotransmitters, it has been
      hypothesized that they may also mediate the desire to drink alcohol by acting on
      specific receptors in the brain. Animal studies have shown that concomitant
      administration of 5-HT and opioid antagonists reduces alcohol consumption;
      therefore, the combined use of several pharmacotherapies may be the most
      effective treatment for alcohol dependence.

PMID- 8736999
TI  - Implications of endogenous opioids and dopamine in alcoholism: human and basic
      science studies.
AB  - We investigated the endogenous opioid system and its role in mediating the
      reinforcing effects of ethanol that lead to high ethanol consumption as a
      biochemical marker of an individual's vulnerability to excessive ethanol
      consumption. We performed studies using human subjects with [high risk (HR)] and
      without [low risk (LR)] a family history of alcoholism to supplement our studies
      with experimental animals bred selectively for high- or low-ethanol consumption.
      HR subjects had lower basal plasma beta-endorphin levels as compared with LR
      subjects, but they had a more pronounced release of beta-endorphin after exposure
      to ethanol. Findings from animal studies indicated that ethanol-preferring
      (C57BL/6) mice (analogous to the HR human subjects) had higher levels of
      hypothalamic beta-endorphin activity than did ethanol-avoiding (DBA/2) mice
      (analogous to the LR human subjects) under basal conditions. However, the C57BL/6
      mice had a more pronounced release of hypothalamic beta-endorphin than did DBA/2
      mice after exposure to ethanol. Thus, although hypothalamic beta-endorphin system
      activity in human and animal models of alcoholism differs under basal conditions,
      there is enhanced hypothalamic beta-endorphin system activity after exposure to
      ethanol in both models. We have also performed studies comparing the density and
      distribution of opioid receptors in brains of ethanol-preferring animals, such as
      C57BL/6 mice and ALKO-alcohol (AA) rats, and ethanol-avoiding animals, such as
      DBA/2 mice and ALKO-non-alcohol (ANA) rats. Interestingly, it was observed that
      in distinct brain regions known to be important for mediating the process of
      reinforcement, the C57BL/6 mice had a higher density of delta-opioid receptors
      than the DBA/2 mice, while the AA rats had a higher density of mu-opioid
      receptors than the ANA rats. Thus, in the ethanol-preferring animals, the
      increased release of beta-endorphin following exposure to ethanol was associated
      with a higher density of delta- or mu-opioid receptors in brain regions important
      for reinforcement, such as the nucleus accumbens and the ventral tegmental area,
      and may interact with the dopaminergic system and promote ethanol's reinforcing
      properties, leading to excessive drinking and alcoholism.

PMID- 8737000
TI  - Neurobehavioural basis for the pharmacotherapy of alcoholism: current and future
      directions.
AB  - Results from studies of pharmacotherapies for primary alcoholism are reviewed,
      including selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors
      (e.g. fluoxetine), opiate antagonists (e.g. naltrexone) and dopamine agonists
      (e.g. bromocriptine). Because there is considerable comorbidity between alcohol
      dependence, anxiety, and affective disorders, results from studies of medications
      used to treat these psychiatric disorders are also reviewed, including the 5-HT
      agonist buspirone and the noradrenergic agent desipramine. The neurobehavioural
      model of alcohol dependence implies that combinations of medications may lead to
      more effective treatment; thus, identifying subtypes of alcoholic patients will
      be important in determining which therapies or combinations of therapy will be
      most effective in treating alcohol dependence. For example, in an ongoing study,
      we are attempting to subtype an alcoholic population for treatment selection by
      measuring endogenous opioid activity. Because endogenous opioids are involved in
      analgesia, we exposed male and female subjects with alcoholism [some of whom had
      post-traumatic stress disorder (PTSD)] to cold-induced pain and measured their
      response before and after administration of naloxone or placebo. The naloxone
      injection reduced pain response. In addition, women who have PTSD are much more
      sensitive to stress, which may be related to levels of brain opioid activity.

PMID- 8737001
TI  - The pharmacological treatment of alcohol dependence: needs and possibilities.
AB  - Standard treatment for alcohol abuse may include pharmacotherapy to alleviate
      withdrawal symptoms followed by psychotherapy in inpatient and/or outpatient
      settings. Treatment goals include abstinence and reduced alcohol consumption.
      Standard treatment for alcoholism has a high rate of success in Germany; however,
      for various reasons, only a small percentage of alcoholic patients are admitted
      to alcoholism treatment programmes. A new drug, acamprosate, could benefit many
      more alcoholic patients. Several studies indicate that acamprosate reduces the
      craving for alcohol and enhances abstinence. Acamprosate's effect is dose
      dependent and it has a few minor side-effects. In addition, the availability of
      acamprosate may enable family practitioners to play an increasingly important
      role in the treatment of alcoholic patients, thus allowing more patients to
      receive treatment.

PMID- 8737002
TI  - New 'state' markers for the detection of alcoholism.
AB  - Specific laboratory tests can be used to identify patients who are alcohol
      dependent. The laboratory values of a number of biological 'markers', including
      carbohydrate-deficient transferrin, are often elevated in cases of chronic and
      acute alcohol abuse. Trait markers reflect a predisposition for alcoholism; state
      markers reflect actual alcohol consumption. It has been suggested that state
      markers can be subdivided into screening and relapse markers, and even further
      subdivided into pre-relapse markers, i.e. craving markers. We hypothesize that
      methanol metabolism and the presence of condensation products in the blood may
      serve as state and pre-relapse markers for alcoholism. Since the sensitivities
      and specificities of laboratory screening tests vary, and an absolute marker for
      alcoholism has yet to be identified, research in the area of biological markers
      for alcoholism should continue.

PMID- 8737003
TI  - Subtypes of alcoholism and their role in therapy.
AB  - In recent years, the term 'chronic alcoholism' has had a meaning that is more
      descriptive than diagnostic. Several subtypes of alcoholism have been established
      and are now a necessary tool for studying therapy outcome. Alcohol-dependent
      patients can be subtyped based on clearly assigned dimensions (e.g. biological,
      sociological and psychological disturbances). Craving and the underlying
      disturbance must be treated. The number of pharmacological agents that may reduce
      alcohol intake has increased recently. We conducted a prospective long-term study
      based on four subtypes of alcohol-dependent patients to assess the efficacy of
      acamprosate. Our findings demonstrate that these patient subtypes are relevant to
      outcome in trials of pharmacological agents. We strongly recommend subtyping
      alcohol-dependent subjects in future trials, because the usefulness of effective
      drugs could be overlooked when they are tested in a heterogeneous population.

PMID- 8737004
TI  - Use of serotonin (5-hydroxytryptamine) reuptake inhibitors in the treatment of
      alcoholism.
AB  - Animal studies have shown that alcohol consumption is reduced when serotonin (5
      hydroxytryptamine, 5-HT) levels are increased in the central nervous system.
      Similarly, studies of alcohol-dependent human subjects have shown that treatment
      with 5-HT reuptake inhibitors (i.e. zimeldine, citalopram, fluoxetine, and
      fluvoxamine) decreases the desire to drink alcohol and improves symptoms of
      alcohol-related anxiety and depression in patients who have undergone
      detoxification. However, not all studies have shown them to be an effective
      treatment to help maintain recovery in alcohol dependence. The exact mechanisms
      of action of the 5-HT reuptake inhibitors are not yet fully understood and
      additional studies are needed. However, at this time, the 5-HT reuptake
      inhibitors may be effective pharmacotherapies for alcohol-related depression.

PMID- 8737005
TI  - Opioid antagonists in the treatment of alcohol dependence: clinical efficacy and
      prevention of relapse.
AB  - Placebo-controlled studies have demonstrated that patients treated with opioid
      antagonists had fewer drinking days, lower rates of resumed heavy drinking, and
      reduced alcohol craving, when compared with placebo-treated patients. Patients
      who received an opioid antagonist were also less likely to drink heavily if they
      sampled alcohol during treatment. One study also demonstrated that patients who
      were treated with the opioid antagonist naltrexone had lower serum aspartate
      aminotransferase and alanine aminotransferase levels than placebo-treated
      patients. This is consistent with self-reported decreases in alcohol consumption.
      These patients also had less severe alcohol-related problems than placebo-treated
      patients, as indicated by the Addiction Severity Index. Opioid antagonists might
      act by reducing the reinforcing effects of alcohol and the incentive to drink.
      These agents, when combined with comprehensive treatment programmes, are an
      effective adjunctive treatment for alcohol-dependent patients.

PMID- 8737006
TI  - Voice of the victims--the key to consensus and support for alcoholism research.
AB  - The US National Institute on Alcohol Abuse and Alcoholism (NIAAA) recognizes two
      forms of problematic drinking: 'willful alcohol abuse', a behavioural problem,
      and 'alcohol dependence', a true medical disorder, which includes a genetic
      component, that can be scientifically understood and medically treated. Current
      biomedical research has linked specific neurotransmitters to certain effects of
      alcohol that are unique to alcoholics. An inadequate flow of information between
      the victims of alcoholism, researchers, and the public has impeded further
      exploration of the genetic and neurochemical underpinnings of alcohol dependence.
      This is due in part to continuing misconceptions about alcohol dependence, not
      only among the general public, but within the scientific and medical communities
      as well. Consequently, compared to other diseases, research in alcohol dependence
      is proceeding with less urgency despite its relatively high economic and social
      costs. Incorporating the input of recovering alcoholics into future research
      agendas can help to ensure relevant scientific investigation and the delivery of
      a more accurate and consistent message to the public with regard to alcoholism.

PMID- 8737007
TI  - The treatment of alcoholic hepatitis.
AB  - Alcoholic hepatitis is a precirrhotic lesion; it develops in only a minority of
      chronic alcohol abusers even after decades of abuse. The clinical spectrum of
      disease varies from asymptomatic hepatomegaly to florid hepatocellular failure
      with gastrointestinal bleeding and hepatic encephalopathy. Corresponding
      variation is observed both in morbidity and mortality. The majority of
      individuals with mild to moderate alcoholic hepatitis improve significantly
      following abstinence from alcohol and the provision of a diet sufficient to meet
      their nutritional requirements; their long-term outcome is determined largely by
      their ability to maintain abstinence from alcohol. Individuals with severe
      alcoholic hepatitis require intensive nutritional support and vigorous management
      of the complications of their liver injury; their outcome is generally poor. A
      small, carefully selected subgroup of these very sick patients may benefit, at
      least in the short-term, from treatment with corticosteroids; the place of
      orthotopic hepatic transplantation, in this patient group, is still the subject
      of debate. No other treatment modalities have been shown to confer benefit
      consistently. A number of new therapeutic approaches have been proposed and need
      to be explored.

PMID- 8737008
TI  - Alcohol-related seizures and the kindling effect of repeated detoxifications: the
      influence of cocaine.
AB  - The purpose of this study was to determine if individuals with concurrent alcohol
      and cocaine use differ in regard to seizure risk compared to individuals who
      abuse only alcohol, and to explore the relationship between multiple
      detoxifications and seizure risk in the context of concurrent cocaine use. In
      this study, alcoholic cocaine users had a decreased risk of seizure compared to
      alcoholics without cocaine use (P < 0.005). Seizures were rare in individuals who
      did not abuse alcohol. Alcoholic cocaine users reported a younger age at first
      seizure compared to alcoholics without cocaine use (P < 0.04). Alcoholic patients
      with seizures had significantly more previous detoxification experiences compared
      to matched alcoholic patients without seizures (P = 0.0001). Concurrent cocaine
      use did not appear to have an independent effect on the risk of seizure. The
      findings in this study suggest that concurrent cocaine use may accelerate the
      development of alcohol-related seizures in predisposed individuals but does not
      appear to substantially increase overall risk. Multiple previous detoxifications
      are associated with an increased risk of seizures in alcoholics both with and
      without concurrent cocaine use.

PMID- 8737009
TI  - Are alcoholic women more likely to drink premenstrually?
AB  - A retrospective questionnaire study of alcoholic women attending a clinic for
      abstaining alcoholics, a voluntary agency and a drop-in centre for people with
      alcohol problems was conducted over a 2-year period. The women were asked whether
      they experienced premenstrual symptoms based on Halbreich et al.'s Premenstrual
      Assessment Form (PAF) [Halbreich et al. (1982) Acta Psychiatrica Scandinavica 65,
      46-65] and were also administered the severity of Alcohol Dependence
      Questionnaire (SADQ). The results showed that one-third of women drank more
      premenstrually than at other times of the month. It is concluded that knowledge
      of high-risk times of the month can aid counselling for this group of women.

PMID- 8737010
TI  - Buspirone as an inhibitor of voluntary ethanol intake in male rats.
AB  - The effect of buspirone, a drug with mainly 5-HT1A-agonist activity, on voluntary
      ethanol intake was tested in a rat model of alcoholism. In this model the
      treatment consists of an injection of ethanol (2.0 g/kg) or saline once a week,
      preceded by a 24 h choice between water and ethanol (10% w/v). This weekly
      injection of ethanol reduces voluntary ethanol intake in male rats. Maximal
      inhibition is seen after 5-6 weeks. At this maximal inhibition buspirone or
      saline was injected prior to the voluntary 24 h intake of ethanol in both the
      ethanol- and saline-injected groups. The tested doses were 5 mg/kg (week 5) and
      20 mg/kg (week 6). There was no reduction in ethanol intake in the buspirone
      injected groups when compared with their corresponding controls. A second
      experiment with buspirone was performed during the evaluation period following
      treatment with ethanol. This treatment consisted of a choice between water and
      ethanol (10%, w/v) for 1 day each week, followed by an injection of ethanol 2.0
      g/kg) and lasted for 52 weeks. During the evaluation period the rats had a
      continuous choice between ethanol and water for 37 weeks and no injections were
      given. In this situation, with a longer exposure to ethanol, a dose of 20 mg/kg
      of buspirone in week 90 reduced ethanol intake by approximately 40%, when
      compared with controls. The effect of this buspirone dose lasted at least a week.
      This indicates that the long-term exposure to ethanol in the second experiment
      induces changes that affect the serotonergic transmission, and that this changed
      neural system is involved in the regulation of voluntary ethanol intake.

PMID- 8737011
TI  - Relative and combined effects of propylthiouracil, ethanol and protein deficiency
      on muscle.
AB  - A hypermetabolic state with increased oxygen consumption has been described in
      alcoholic hepatitis, playing a major role in ethanol-induced liver damage. Based
      on its ability to decrease oxygen consumption, propylthiouracil (PTU) has been
      proposed as a therapeutic agent in this context. On the other hand, several
      muscle changes have been described in hypothyroidism, including both atrophy and
      hypertrophy of muscle fibres. The aim of this experimental study was to analyse
      the effects of PTU on the alcohol-induced changes in muscle fibre size and
      proportion, also taking into account the presence or absence of protein
      deficiency. The study was performed on 64 male Wistar rats divided into eight
      groups, fed with: (1) Lieber-DeCarli control diet: (2) an isocaloric 36% ethanol
      containing diet: (3) an isocaloric 2% protein-containing diet: (4) an isocaloric
      36% ethanol 2% protein-containing diet, without and with PTU, respectively. Right
      gastrocnemius muscle was removed 2 months later and histochemical and
      morphometric studies were performed. Type IIb fibre atrophy was observed both in
      the alcoholic and protein-deficient animals, but not in the PTU-treated animals.
      The combination of protein deficiency and ethanol led to a more marked type IIb
      atrophy, with PTU reversing this effect. Malnutrition led to a decrease in type I
      fibre diameter: ethanol and PTU caused an increase in its size and PTU reversed
      the effect of protein deficiency. Proportion of type IIb fibres decreased in the
      three experimental groups without PTU with respect to the control, especially in
      the alcoholic protein-deficient animals. PTU-treated animals, especially those
      fed a low-protein diet, showed a more marked reduction in type IIb fibre
      proportion than that presented by the groups without PTU. However, an increase in
      type I fibre proportion was observed in the PTU-treated animals, especially
      marked in those fed a low-protein diet. Thus, PTU seems to ameliorate ethanol
      induced changes on type IIb muscle fibres.

PMID- 8737012
TI  - Distribution of catalase in rat brain: aminergic neurons as possible targets for
      ethanol effects.
AB  - Ethanol is metabolized at a slow but measurable rate in rodent brain. Recent
      studies indicate that this process is mediated mainly by catalase. The spatial
      distribution of this enzyme in different brain structures is poorly known. To
      explore possible local imbalances between the production and elimination of
      ethanol-derived acetaldehyde, we investigated the regional and cellular
      distribution of catalase, histo- and immunohistochemically, using serial cryostat
      sections from male Wistar rats. Compared to the strong peroxisomal staining seen
      in liver, brain catalase staining was weak and was not immunologically detected
      with an anti-sheep bovine catalase antibody. Activity was observed only in
      microperoxisomes, mainly in perikaryons of aminergic neurons, in the known groups
      of adrenergic, nonadrenergic and serotonergic neurons of the brain stem. Little
      peroxisomal staining was seen in other types of brain structures. This result
      contrasted to that of aldehyde dehydrogenase, which we previously observed to be
      widely distributed in brain structures, but with low activity in perikaryons of
      aminergic (especially catecholaminergic) neurons, as compared to cholinergic
      neurons. Our data indicate that catalase-mediated oxidation of ethanol to
      acetaldehyde takes place mainly in aminergic neurons, which seem to have a
      limited capacity for the subsequent removal via aldehyde dehydrogenase. This
      suggests that locally produced acetaldehyde could mediate CNS effects of ethanol
      in these structures.

PMID- 8737013
TI  - Adrenalectomy protects ethanol-withdrawn rats from harmine-induced tremor.
AB  - A growing number of studies have implicated the hypothalamic-pituitary-adrenal
      (HPA) axis in acute and chronic alcoholization and in ethanol withdrawal. In
      order to study the ethanol/HPA axis interaction during alcohol withdrawal, we
      performed experiments using adrenalectomized (ADX) male rats alcoholized by a
      chronic pulmonary alcoholization procedure. Eight hours after the 3 weeks of the
      alcoholization procedure, the rats were evaluated for a tremor activity. In order
      to reduce the great variability of the withdrawal tremors, we estimated the
      supersensitivity of the withdrawn rats to the tremorogenic compound harmine. We
      also studied the effect of a hydrocortisone treatment given in the drinking
      bottle during the alcoholization procedure on the harmine-induced tremors of ADX
      and sham rats. Alcohol withdrawal resulted in increased tremor response to 10
      mg/kg harmine, and a protective effect of adrenalectomy on this effect was
      observed. Hydrocortisone administration to ADX or sham rats did not affect the
      tremor profile of the alcohol withdrawn rats.

PMID- 8737014
TI  - Age-related effects of chronic ethanol intake on physical properties, lipid
      composition and galactosyltransferase activity of rat small intestine microsomes.
AB  - The effect of a 4-week ethanol administration on: (1) glycoprotein content of
      brush border membrane (BBM): (2) galactosyltransferase activity; (3) lipid
      composition and fluidity of intestinal microsomes prepared from young and adult
      rats was investigated. In spite of a lower alcohol consumption, the more dramatic
      effects of treatment have been observed in the older rats, where BBM protein
      bound hexoses and microsomal galactosyltransferase activity were significantly
      decreased. On the contrary, these parameters were unaffected in young rats.
      However, both rat groups were similarly affected in having their microsomal
      cholesterol contents significantly increased. Microsomal membranes from ethanol
      fed adult rats were less fluid compared to control rats: the high fluorescence
      anisotropy value could be related to the high cholesterol/phospholipid ratio and
      to the decrease of the unsaturated fatty acids C22:4 and C22:6.

PMID- 8737015
TI  - Prevalence of alcohol problems in general practice: an experience from southern
      Italy.
AB  - The Michigan Alcoholism Screening Test (MAST) and the response to a question
      about heavy alcohol consumption were used to assess the prevalence of alcohol
      problems in consecutive patients (77 males and 46 females) consulting a general
      practitioner in an urban area in the South of Italy (Castellammare di Stabia).
      Alcohol problems, which were defined by a cut-off score of 5 on the MAST and/or
      by heavy alcohol consumption (corresponding to at least 60 g of ethanol daily for
      males and 36 g of ethanol daily for females for at least 2 years), were
      identified in 54 patients [43.9%; 95% confidence interval (CI) 35.0-53.1%], 45
      males (58.4%; 95% CI 46.6-69.6%) and nine females (19.6%; 95% CI 9.4-33.9%). The
      prevalence of MAST positive patients was 32.5% (95% CI 24.4-41.6%) in the total
      patient sample, 45.5% (95% CI 34.1-57.2%) among males and 10.9% (95% CI 3.6
      23.6%) among females. The question about heavy alcohol consumption had a
      predictive negative value of 97.2% (95% CI 90.2-99.7%) and a predictive positive
      value of 73.1% (95% CI 59.0-84.4%) in relation to MAST positive patients. It is
      suggested that general practitioners should incorporate this question about heavy
      alcohol consumption as a screening question in order to detect alcohol problems
      and give advice regarding reduction of alcohol consumption.

PMID- 8737016
TI  - Urinary excretion of tetrahydro-beta-carbolines relating to ingestion of
      alcoholic beverages.
AB  - Tetrahydro-beta-carbolines, formed from aldehydes and tryptamine, have been
      suggested as potential biochemical markers for alcoholism. The excretion of 1
      methyl-1,2,3,4-tetrahydro-beta-carboline (MTBC) and 1,2,3,4-tetrahydro-beta
      carboline (TBC) in human urine was studied to assess their possible origin. In
      urine collected after a drinking party, MTBC and TBC were excreted in
      significantly higher concentrations compared with sobriety. MTBC and TBC were
      contained in beer and wine at ng/ml levels, but not in distillate alcoholic
      beverages such as whisky, brandy, gin, etc. The urinary excretion of MTBC and TBC
      was elevated after drinking beer, whereas no change was observed after drinking
      whisky. When a human subject was orally administered with deuterated L-tryptophan
      together with drinking whisky, deuterated tryptamine was increasingly excreted in
      urine. However, no increase was found in urinary deuterated MTBC. These results
      indicate that the urinary excretion of MTBC and TBC associated with alcohol
      ingestion does not imply promotion of their in vivo formation, but the exogenous
      supply of MTBC and TBC by drinking alcoholic beverages containing them.

PMID- 8737017
TI  - Effects of chronic administration and subsequent withdrawal of ethanol-containing
      liquid diet on rat liver tryptophan pyrrolase and tryptophan metabolism.
AB  - An investigation of the effects of chronic administration of ethanol by the
      liquid diet procedure and its subsequent withdrawal on tryptophan (Trp)
      metabolism and disposition was performed in rats. Treatment with the control
      liquid diet caused an enhancement of liver Trp pyrrolase activity and mRNA
      abundance. These effects are not due to the starvation associated with this
      feeding procedure, because they occur in rats maintained on the liquid diet ad
      libitum. Chronic ethanol administration in the liquid diet did not further
      influence the above increased expression of Trp pyrrolase mRNA but caused
      inhibition of pyrrolase activity in competition with the effects of the diet. The
      control liquid diet decreased liver Trp concentration, but exerted no significant
      effects on other aspects of Trp disposition. The most striking and robust finding
      was a highly significant elevation in both Trp pyrrolase activity and mRNA
      expression at 7 h following discontinuation of ethanol availability, at which
      time there were demonstrable behavioural signs of ethanol withdrawal. The
      increase in Trp pyrrolase mRNA during alcohol withdrawal may be caused by
      corticosterone, whose circulating concentration was also increased. The changes
      in Trp pyrrolase activity during ethanol withdrawal were associated with
      significant alterations in Trp disposition including decreased brain Trp
      concentration and 5-hydroxytryptamine synthesis and turnover. These alterations
      may play a pivotal role in the behavioural manifestations of ethanol withdrawal
      including the hyperexcitement underlying audiogenic seizures. We suggest that rat
      Trp pyrrolase gene regulation may be an important biological determinant of the
      ethanol withdrawal syndrome and requires further study, and that the use of the
      liquid diet procedure in Trp metabolic studies requires inclusion of adequate
      controls and special attention to the effects of the liquid diet itself.

PMID- 8737018
TI  - Acetylcholinesterase and choline uptake in striatum from rats with varying
      sleeping times.
AB  - Male rats were injected with ethanol as a 25% solution (3.5 g/kg body weight) and
      then the duration of the retention of the righting reflex (DRR) as well as the
      duration of ethanol-induced sleep (DEIS) were recorded. On the basis of DEIS in
      60 rats, we selected four groups of six rats each: short-sleep group (SS, 34 +/-
      5 min), intermediate-sleep (IS, 118 +/- 3 min), long-sleep (LS, 186 +/- 5 min)
      and non-sleep rats (NS, 0 min). The striatal crude mitochondrial fraction was
      assayed for acetylcholinesterase activity (AChE, EC 3.1.1.7) and high-affinity
      choline uptake. NS rats manifested similarity of the above parameters to those
      determined in SS and IS rats. LS rats were distinguished by a higher AChE
      activity in comparison with NS animals.

PMID- 8737019
TI  - Ethical issues in research into prevention of insulin-dependent diabetes mellitus
      (IDDM)

PMID- 8737020
TI  - The management of hypertension in diabetes: with special reference to diabetic
      kidney disease.
AB  - Hypertension is both an exacerbating factor for, and a consequence of, diabetic
      renal disease. In diabetic patients, hypertension is associated with increased
      total body sodium secondary to impaired renal excretion, and increased vascular
      reactivity, notably to catecholamines and angiotensin II. The mechanisms causing
      these changes are discussed. Control of hypertension will slow the progression of
      diabetic renal disease and the inexorable decline in GFR. A number of studies now
      suggest that in proteinuric IDDM and NIDDM patients angiotensin converting enzyme
      inhibitors (ACE-I) may have additional reno-protective effects in addition to
      their hypotensive action. In addition ACE-I will reduce proteinuria and delay the
      onset of diabetic nephropathy in normotensive microalbuminuric IDDM and NIDDM
      patients. Use of ambulatory blood pressure monitoring indicates that such
      patients may not be truly 'normotensive'. On-going studies seem to suggest that
      the most reno-protective blood pressure is the lowest one achievable, as long as
      the patient remains asymptomatic. Further studies are required to assess the
      impact of blood pressure control, and especially ACE-I, on the incidence of end
      stage renal failure. In addition, more direct comparisons between different
      pharmacological agents in early diabetic renal disease would be useful.

PMID- 8737021
TI  - R.D. Lawrence, H.G. Wells, G.B. Shaw: a vignette.
AB  - Among the unpublished autobiographical notes of Dr R.D. Lawrence are numerous
      references to his contacts and friendship with the author H.G. Wells, who was to
      become the first President of the (British) Diabetic Association. Wells was
      responsible for Lawrence being called in for consultation by George Bernard Shaw,
      a meeting which was to have surprising consequences.

PMID- 8737022
TI  - In new-onset insulin-dependent diabetic patients the presence of anti-thyroid
      peroxidase antibodies is associated with islet cell autoimmunity and the high
      risk haplotype HLA DQA1*0301-DQB1*0302. Belgian Diabetes Registry.
AB  - In 157 new onset IDDM (104 men, 53 women, ages 10-39 yr) anti-thyroid peroxidase
      anti-bodies (anti-TPO) were assayed with a specific immunological test. Values
      greater than 100 U ml-1 were considered positive. Seventeen per cent of the
      patients were positive (32% of the women versus 10% of the men, p < 0.001).
      Eighty-five per cent of the anti-TPO + patients have a positive titre of islet
      cell antibodies (ICA > or = 12 JDFU) versus 64% of the anti-TPO-patients (p <
      0.05). When patients were subdivided in a young (10-25 yr) and an older age group
      (26-39 yr) this association was also true for ICA > or = 50 JDFU and valid for
      insulin autoantibodies (IAA) at low (> or = 0.7%) and high risk (> or = 1.5%) (p
      < 0.005) in the second group. The median of the TSH concentration was not
      different between anti-TPO+ and anti-TPO- when the group is considered as a
      whole. In the anti-TPO+ men (26-39 yr) TSH was however significantly greater
      (1.55 microU ml-1, range 0.74-8.5 versus 1.4 microU ml-1, range 0.21-3.5, p <
      0.0001) when compared to the anti-TPO-men of the same age group. The haplotype
      HLA DQA1*0301-DQB1*0302 was more frequent in the anti-TPO+ (39%) than in the anti
      TPO- (23%) patients (p < 0.02) for the age group 26-39 yr but not for the age
      group 10-25 yr. The other diabetes susceptibility haplotype DQA1*0501-DQB1*0201
      was less frequent in anti-TPO+ patients. In conclusion we suggest that thyroid
      auto-immunity must be part of the initial screening of IDDM especially when
      patients are older at clinical onset of the disease.

PMID- 8737023
TI  - Evaluation of the importance of maternal history of diabetes and of mitochondrial
      variation in the development of NIDDM.
AB  - In 79 South Indian nuclear pedigrees ascertained via probands with NIDDM and both
      parents living, parental diabetic status was established through previously
      diagnosed NIDDM (n = 97) or oral glucose tolerance testing (n = 61). There was no
      significant difference between diabetes prevalence in mothers and fathers (60 vs
      53 (76% vs 67%), respectively, p = 0.22). 'Age at diabetes diagnosis' survival
      curves did differ according to parental gender (p = 0.02) but this may reflect
      gender differences in health provision rather than pathophysiology. No maternal
      excess effects of the magnitude evident in previous studies were detected,
      suggesting either ethnic differences or overestimation of the maternal effect
      when reported histories of parental diabetes have been used. The tRNA(Leu(UUR)
      gene region was studied for diabetes-associated variation given the role of
      mutations in this gene in some pedigrees displaying maternal transmission of
      NIDDM. None of 142 unrelated South Indian NIDDM subjects displayed the MELAS
      mutation at nt3243. However, sequencing identified two variants of potential
      importance: (a) at nt3290 in the tRNA(Leu(UUR) gene, seen in 7/142 diabetic and
      1/85 control subjects (p = 0.11), (b) at nt3316 in the ND1 gene (4/142 vs 1/85
      subjects, respectively (p = 0.51)). Further studies are needed to determine the
      relevance of these variants to the development of NIDDM.

PMID- 8737024
TI  - The short insulin tolerance test: feasibility study using venous sampling.
AB  - The short insulin tolerance test (ITT) is both a simple and valid method of
      quantifying insulin sensitivity although arterialization of samples and the risk
      of hypoglycaemia remain as potential difficulties. We examined the safety and
      reproducibility of using venous sampling with insulin doses of 0.1 U kg-1 and
      0.05 U kg-1 in healthy subjects. Whole blood glucose concentrations were measured
      contemporaneously and the rate of plasma glucose decline (mmol l-1 min-1) for
      each test was estimated from unlogged venous plasma glucose concentrations
      measured at 1 min intervals. The mean rates of plasma glucose decline for the 0.1
      U kg-1 and 0.05 U kg-1 insulin doses were 0.26 mmol l-1 min-1 (n = 11, range =
      0.17-0.41, intrasubject coefficient of variation (CV) = 9.4%) and 0.25 mmol l-1
      min-1 (n = 6, range 0.19-0.46, intrasubject CV = 15.9%), respectively. Reversal
      of significant hypoglycaemia was necessary in one subject before 15 min post
      insulin. We found that: (1) venous sampling provides a reproducible measure of
      glucose uptake after insulin, (2) contemporaneous bedside glucose sampling
      identifies those at risk of significant hypoglycaemia during the ITT, and (3) the
      0.1 U kg-1 dose response is more reproducible and no less safe than the half dose
      response. We conclude that the current ITT protocol would be made safer and
      simpler with the above modifications although further studies comparing venous
      with arterialized sampling are needed.

PMID- 8737025
TI  - Metabolic abnormalities in offspring of NIDDM patients with a family history of
      diabetes mellitus.
AB  - NIDDM appears to be an inherited condition. Our aim was to identify early
      metabolic abnormalities in non-diabetic offspring with one NIDDM parent and with
      a strongly positive (n = 58, age 27.8 +/- 7.0 years) or a negative family history
      (n = 38, age 27.4 +/- 6.7 years) of diabetes. These were compared with 31
      offspring of non-diabetic parents (age 26.9 +/- 5.5 years). After an overnight
      fast, blood was taken for glucose, insulin, C-peptide, insulin receptors, and
      lipids. All the subjects underwent a 75 g oral glucose tolerance test. The
      positive family history group had significantly higher fasting levels of
      triglycerides (1.09 +/- 0.24 vs control subjects: CS: 0.93 +/- 0.16 mmol l-1, p <
      0.001), insulin (102.8 +/- 46.4 vs CS: 77.5 +/- 32.4 pmol l-1, p < 0.01) and C
      peptide (0.69 +/- 0.22 vs CS: 0.61 +/- 0.19 nmol l-1, p < 0.05) and lower numbers
      of insulin receptors per red cell (9.1 x 10(3) (4.5-18.1, 95% confidence
      intervals) vs CS: (11.2 x 10(3) (6.3-19.9)), p < 0.01, despite similar blood
      glucose levels. After a glucose challenge (120 min), the increases in both
      insulin and C-peptide concentrations were significantly greater in the positive
      family history group (289.2 +/- 214.1 pmol l-1, 2.23 +/- 1.48 nmol l-1),
      respectively, than in CS (192.4 +/- 170.3 pmol l-1, p < 0.05) (1.54 +/- 0.99 nmol
      l-1 p < 0.01), respectively. No significant differences were found in fasting and
      post-challenge glucose levels. The negative family history group had
      significantly lower numbers of insulin receptors 9.4 x 10(3) (4.1-15.2) compared
      with CS (p < 0.05). Insulin sensitivity was significantly reduced in the positive
      family history group (41.6%) compared with control subjects (51.9%), p < 0.01.
      The results strongly support the familial basis of the disease.

PMID- 8737026
TI  - Microalbuminuria, cardiovascular risk factors, and insulin resistance in two
      populations with a high risk of type 2 diabetes mellitus.
AB  - A total of 359 Wanigelas from Papua New Guinea and 1041 Nauruans had urinary
      albumin concentrations (UAC), serum insulin, and a number of cardiovascular
      disease (CVD) risk factors measured during population-based surveys of non
      insulin-dependent diabetes mellitus. These data were used to explore the
      hypothesis that microalbuminuria is closely associated with insulin resistance
      and the metabolic syndrome. In both Nauruans and Wanigelas, worsening glucose
      tolerance was associated with increasing prevalence of micro- and
      macroalbuminuria. Within each category of glucose tolerance, microalbuminuria was
      associated with general worsening of cardiovascular risk factors including lipid
      concentrations, blood pressure and obesity, although few of the associations were
      statistically significant. Correlations between UAC and markers of insulin
      resistance (fasting insulin, fasting insulin/glucose ratio and HOMAS%, a computer
      modelled estimate of insulin sensitivity) were weak and inconsistent irrespective
      of glucose tolerance status. Relationships between insulin sensitivity and
      urinary albumin in normoglycaemic Wanigelas and Nauruans, and in diabetic
      Nauruans, were no longer significant after adjusting for fasting glucose and body
      mass index. While microalbuminuria in Nauruans and Wanigelas was associated with
      cardiovascular risk factors irrespective of glucose tolerance, it seems unlikely
      on the basis of these results that the relationship is mediated through a common
      association with insulin resistance.

PMID- 8737027
TI  - Clinical characteristics, left and right ventricular ejection fraction, and long
      term prognosis in patients with non-insulin-dependent diabetes surviving an acute
      myocardial infarction.
AB  - Patients with diabetes mellitus have a high morbidity and mortality from acute
      myocardial infarction, the reason for which is not fully understood. The
      relationship between congestive heart failure symptoms, left ventricular ejection
      fraction, and long-term mortality was examined in 578 hospital survivors of acute
      myocardial infarction, 47 of whom had Type 2 (non-insulin-dependent) diabetes
      mellitus. None of the patients were treated with insulin. The prevalence of
      congestive heart failure during hospitalization was similar in patients with and
      without diabetes, although mean diuretic dose was higher in the former patients.
      Left and right ventricular ejection fraction was measured with radionuclide
      ventriculography in the second week after acute myocardial infarction. At
      discharge from the coronary care unit, patients with and without diabetes had
      similar left ventricular ejection fraction (with diabetes: median 46% vs without
      diabetes: median 43%; p = 0.89). Median right ventricular ejection fraction (62%)
      was within normal limits in both groups and did not differ statistically.
      Survival data were obtained for all patients. The 5-year mortality was increased
      in patients with diabetes compared with non-diabetic patients independent of left
      ventricular ejection fraction. Univariate analysis showed that the cumulative 5
      year mortality rate was 53% in the group with diabetes compared with 43% in the
      non-diabetic group (p = 0.007). Using multivariate regression analysis presence
      of diabetes was found to have a significant association with long-term mortality
      after myocardial infarction, that was independent of age, history of
      hypertension, congestive heart failure symptoms during hospitalization or of
      either left or right ventricular ejection fractions at discharge. We conclude
      that the excess mortality in patients with non-insulin-dependent diabetes
      mellitus is not explained by available risk markers after myocardial infarction.
      Even though left ventricular ejection fraction and serum creatinine did not
      differ significantly, the apparent higher dose of Frusemide in patients with than
      without non-insulin-dependent diabetes mellitus might indicate that heart
      failure, it present, is more severe in patients with than in those without
      diabetes. The importance of diastolic dysfunction in this context needs to be
      determined.

PMID- 8737028
TI  - Influence of diabetes mellitus and glycaemic control on the characteristics and
      outcome of common infections.
AB  - The aim of the present study was to elucidate the effect of diabetes and
      metabolic control on the presentation, sources, pathogens and outcome of common
      infections. Of 515 patients admitted to three departments of internal medicine
      because of a suspected acute infection, 132 (26%) had diabetes mellitus.
      Osteomyelitis was diagnosed in 3% of the diabetic patients and in 1% of patients
      without diabetes, and infection of the extremities in 7% and 0%, respectively (p
      = 0.003). Klebsiella sp. caused 24% of urinary tract infections in diabetic
      patients, versus 13% in patients without diabetes (p = 0.1). The percentage of
      Staphylococcus aureus infections in diabetic patients was 10% versus 5% in non
      diabetic patients (p = 0.06). The gross mortality rate in the diabetic patients
      was 10%, and in patients without diabetes, 12%. In patients without fatal
      underlying disorders, mortality in the diabetic patients was 10% (2% in patients
      with glycosylated haemoglobin (GHb) lower than median, and 17% in patients with
      GHb higher than median) and in the non-diabetic patients 4% (p = 0.04). Five
      factors were independently and significantly related to mortality in diabetic
      patients: acute respiratory distress (very large odds-ratio [OR]), coma (OR 3.8,
      95% confidence interval [CI] 1.0-14.3), GHb above the median (OR 3.3, 95% CI 1.8
      6.2), the interaction between GHb and absence of a severe underlying disorder (OR
      12.0, 95% CI 2.9-50.7) and duration of diabetes (OR of 1.072 for 1-year
      increment, and 1.42 for a 5-year increment). Choice of empiric antibiotic
      treatment in diabetic patients with suspected bacterial infection should take
      into account the preponderance of Klebsiella sp. and Staphylococcus aureus
      infections. The present results favour an association between poor glycaemic
      control and a fatal outcome of infectious diseases in diabetic patients.

PMID- 8737029
TI  - Coeliac disease: frequent occurrence after clinical onset of insulin-dependent
      diabetes mellitus. Childhood Diabetes in Finland Study Group.
AB  - Coeliac disease was searched for in a series of 776 children with newly diagnosed
      IDDM. During the follow-up of 2 to 3 years from diagnosis, reticulin and gliadin
      antibodies were measured, and a jejunal biopsy was performed in those cases with
      high levels of antibodies; 19 children were identified with coeliac disease,
      giving the prevalence of 2.4%. In only one case had coeliac disease been
      diagnosed before IDDM. Nine patients with proven coeliac disease were negative
      for antibodies when IDDM was diagnosed, but became positive within 24 months. All
      patients found to have coeliac disease were positive for IgA reticulin
      antibodies, but only 12 of 18 (67%) showed a high level of IgA gliadin
      antibodies. Of the 18 patients genotyped for HLA DR locus, 14 (78%) were positive
      for DR3 and 10 (56%) were positive for DR4. DQB1*0201 allele was present in 17 of
      18 patients (94%). Coeliac disease in children with IDDM tends to develop soon
      after diabetes is diagnosed. Routine screening for coeliac disease is recommended
      repeatedly during the first years after the diagnosis of IDDM.

PMID- 8737030
TI  - Daytime glibenclamide and bedtime NPH insulin compared to intensive insulin
      treatment in secondary sulphonylurea failure: a 1-year follow-up.
AB  - The aim of this study was to compare the metabolic effects of a combination of
      daytime glibenclamide and evening NPH insulin with intensive insulin treatment
      (rapid acting insulin before meals and NPH insulin at bedtime) in patients
      exhibiting secondary failure to sulphonylurea treatment. Thirty-nine mildly obese
      NIDDM patients (BMI 25.6 +/- 0.5) were randomized after 6 weeks of intensive
      insulin treatment to either a combination treatment (CT, n = 20) or continued
      intensive insulin treatment (IT, n = 19). There were no differences between the
      two groups in age, diabetes duration, BMI, HbA1c, or basal and glucagon
      stimulated C-peptide. The patients were followed for 1 year and the findings were
      analysed on an intent to treat basis. Two patients in the CT group were excluded
      after 2 and 6 months, respectively, due to unacceptably high postprandial glucose
      values. There was a significant difference in HbA1c between the CT and IT groups
      at 6 months (8.2 +/- 0.2, n = 19, vs 6.8 +/- 0.4%, n = 19, p < 0.001)), but not
      at 12 months (7.8 +/- 0.3, n = 18, vs 7.5 +/- 0.4%, n = 19). After the initial
      intensive insulin treatment, BMI was constant in the CT group but increased
      significantly at 6 and 12 months in the IT group. We conclude that both
      treatments are associated with a marked and long-term improvement of glycaemic
      control. The intensive insulin treatment leads to a more pronounced weight
      increase which in the long run might have negative effect on overall metabolic
      control. Therefore, the combination treatment together with intensified education
      and dietary advice should be regarded as the initial treatment of choice for oral
      agent failure in moderately obese NIDDM patients.

PMID- 8737031
TI  - Increased prevalence of upper gastrointestinal symptoms in long-term type 1
      diabetes mellitus.
AB  - Using a validated postal questionnaire, we investigated the frequency of 24
      gastrointestinal symptoms during the previous 3 months in a cohort of 110 young
      adult patients (54 males and 56 females, mean age 37.2 +/- 4.7 years) with onset
      of Type 1 diabetes mellitus at < 16 years of age. They were compared with 210 age
      and sex-matched controls (104 males and 106 females). The main difference in the
      frequency of various symptoms between the two groups was a significant increase
      among the diabetic patients in upper gastrointestinal symptoms, such as loss of
      appetite (17.8% vs 3.6%, p < 0.001), early satiety (26.8% vs 6.1%, p < 0.001),
      nausea (22.7% vs 9.1%, p < 0.01) and vomiting (12.2% vs 3.0%, p < 0.01). No
      difference was noted in the frequency of symptoms from the lower gastrointestinal
      tract, apart from a significant increase in the feeling of incomplete defaecation
      (28.6% vs 17.0%, p < 0.04) in the diabetic patients. Patients with levels of
      haemoglobin A1c in the highest quartile had significantly more gastrointestinal
      symptoms than other diabetic patients. Further, the prevalence of symptoms was
      higher in females than in males. In conclusion, long-term Type 1 diabetes is
      accompanied by a markedly increased frequency of upper gastrointestinal symptoms,
      mainly in females and patients with poor metabolic control.

PMID- 8737032
TI  - Retinopathy screening in type 2 diabetes: reliability of wide angle fundus
      photography.
AB  - The purpose of the study was to assess the reliability of mydriatic 60 degrees
      fundus photography in a retinopathy screening programme for Type 2 diabetic
      patients in a primary health care setting. In 323 eligible consecutive Type 2
      diabetic patients above 40 years of age, attending a regional shared care
      diabetes project, mydriatic wide angle fundus photography was compared with
      standardized fundoscopy in dilated pupils as the recommended test for the
      detection of diabetic retinopathy. Fundus photography included two black and
      white transparencies per eye visualizing the central and nasal retinal field.
      Fundoscopy findings and pictures were scored according to modified Wisconsin
      criteria. Fundoscopy revealed in 95/646 eyes (14.7%) some degree of diabetic
      retinopathy. Sensitivity and specificity of fundus photography (omitting
      ungradable transparencies) were 97% for the diagnosis of any diabetic retinopathy
      (DRP). All patients with moderate and severe DRP (Wisconsin grade 3 and worse)
      according to fundoscopy were detected by fundus photography. In conclusion,
      mydriatic wide angle 60 degrees fundus photography, making two pictures per eye,
      can be applied effectively and reliably in the detection of diabetic retinopathy
      in patients with Type 2 diabetes.

PMID- 8737033
TI  - The effect of the non-ionic contrast medium iohexol on glomerular and tubular
      function in diabetic patients.
AB  - The effect of the non-ionic contrast medium iohexol (Omnipaque) on renal function
      was investigated in diabetic patients with signs of peripheral ischaemia. Forty
      six patients, 70 +/- 11 years (mean +/- SD) old, age at diabetes diagnosis 53 +/-
      17 years, and with varying degrees of diabetic nephropathy were studied before 1,
      2, and 30 days after aortobifemoral arteriography. Serum creatinine, creatinine
      clearance, urinary excretion of immunoglobulin G, albumin collagen IV (NC1),
      kappa and lambda chains, alpha-1 microglobulin and Tamm-Horsfall protein were
      evaluated. Within 1 month before and 30 days after arteriography, the glomerular
      filtration rate was measured by clearance of iohexol. The acute effect of the
      radiocontrast medium was an increase in the serum creatinine level in 41 (89%)
      patients, with a more than 25% increase in 12 (26%) patients. The excretion rates
      of immunoglobulin G and albumin decreased, whereas the proximal and distal
      tubular function and the excretion of collagen IV did not change. The increment
      in serum creatinine was associated with the preangiographic renal function (p <
      0.05), a history of heart failure (p < 0.01), but not with age, duration and type
      of diabetes, gender, systolic or diastolic blood pressure, glycated haemoglobin
      (HbAlc) or blood glucose levels. The increase of serum creatinine was associated
      with a pre-existing proximal tubular dysfunction and a worsening of distal
      tubular function. No changes in the parameters measured persisted 30 days after
      angiography. In summary, a transient increment in serum creatinine level after
      arteriography occurred in 89% of diabetic patients. It was associated with the
      preangiographic renal function, a history of heart failure and signs of
      preexisting proximal tubular dysfunction and worsening of distal tubular
      function. However, these changes were reversible.

PMID- 8737034
TI  - Treatment of diabetic gustatory sweating with topical glycopyrrolate cream.
AB  - A 42-year-old insulin-dependent diabetic man presented with severe bilateral
      gustatory sweating associated with a deterioration in his glycaemic control.
      Conventional oral antimuscarinic medication was contraindicated because of his
      cardiac insufficiency. Topical 0.5% glycopyrrolate cream was tried and applied on
      alternate days to his face, which resulted in the complete cessation of his
      gustatory sweating without side-effects. Topical glycopyrrolate cream is an
      effective treatment of diabetic gustatory sweating without the adverse effects
      commonly found with oral anti-muscarinic medication.

PMID- 8737035
TI  - 'Dead in bed' in Norway.

PMID- 8737036
TI  - Testicular germ cell populations in the adult rat after continuous in-vivo
      testicular infusion of inhibin-A and activin-A.
AB  - This study investigated the in-vivo effects of inhibin-A and activin-A on germ
      cell subpopulations in the adult rat testis. Each animal received a total of 2
      micrograms (dose 5 ng/0.5 microliter/h) of activin, inhibin or 0.1% bovine serum
      albumin (vehicle control) delivered intratesticularly into the left testis via a
      cannula connected to an abdominal minipump implant. To establish whether the
      hormones exerted any effect on procarbazine-induced germ cell depletion, a single
      intraperitoneal dose of this agent was given to a group of the rats 24 h after
      the start of testicular infusion of activin or inhibin. Rats were killed 14 days
      later. Inhibin treatment caused a reduction in the number of round spermatids
      without altering serum FSH levels. In procarbazine-treated rats, infusion of
      inhibin reduced the number of pachytene spermatocytes and reduced blood FSH
      levels simultaneously. Infusion of activin had no significant effect on the
      numbers of germ cells, but reduced the number of dead cells in the seminiferous
      tubules of procarbazine-treated rats. The data would therefore suggest that the
      effects of inhibin and activin on the seminiferous epithelium are influenced by
      the testicular microenvironment, and that they are capable of influencing the
      growth and survival of germ cells by both FSH- and non FSH-mediated mechanisms.
      Further experiments are needed to identify the physiological role(s) of inhibin
      and activin in spermatogenesis.

PMID- 8737037
TI  - Clinical and genetic variability in XX sex-reversed patients.
AB  - Three 46, XX hypogonadal subjects are described who exhibited different clinical
      and genetic characteristics. Two patients, with complete sex-reversal, are
      sterile males with hypogonadal features; the third patient, with partial sex
      reversal, presented with a eunuchoid appearance and with ambiguous genitalia.
      Polymerase chain reaction (PCR) amplification of DNA from these patients showed
      the presence of a translocation of the sex-determining region of the Y chromosome
      (Sry) only in the first two patients described.

PMID- 8737038
TI  - Superoxide anion scavenging capacity of human seminal plasma.
AB  - This study has investigated the antioxidant capacity of human seminal plasma due
      to the presence of both high and low molecular weight antioxidant factors.
      Methods for the measurement of superoxide dismutase-like activity (SOD-like) and
      total antioxidant status (TAS) were automated, and had a within-run coefficient
      of variation of 7.3% for SOD-like activity and 4.8% for TAS. In 69 semen samples
      from unselected infertile men, SOD-like activity in seminal plasma ranged from 2
      to 16 U/ml, with a mean of 6.9 +/- 2.8 U/ml. As SOD-like activity was correlated
      positively with levels of citric acid (p < 0.0001), zinc (p < 0.0002) and acid
      phosphatase activity (p < 0.0005), and there was no correlation with fructose
      levels, our results suggest that prostatic secretions are an important source of
      superoxide anion scavengers. Evaluation of SOD-like activity in infertile men
      with accessory sex gland infections (n = 12) showed significantly lower activity
      (p < 0.003) compared to values found in 12 infertile men without signs of
      infection. The values obtained for total antioxidant status (equivalent to the
      antioxidant capacity of alpha-tocopherol analogue) ranged from 1.7 to 2.3 mmol/L,
      with a mean of 2.1 +/- 0.1 (n = 40), reflecting the protective activity of
      ascorbate, urate and albumin, and to a very low extent of glutathione and
      taurine. The data obtained by TAS assay correlated with fructose, a major marker
      of vesicular secretion (p < 0.005), suggesting that low molecular weight
      components with antioxidant capacity derive partly from the seminal vesicles. The
      results indicate that the relative contribution of antioxidant defence systems
      capable of counteracting the deleterious action of superoxide anions, depends on
      the secretory activity of accessory sex glands and is independent of excessive
      ROS production due to increased oxidative stress.

PMID- 8737039
TI  - Glucose is not essential for the occurrence of sperm binding and zona pellucida
      induced acrosome reaction in the mouse.
AB  - Glucose is necessary, in some species, for successful fertilization, but its role
      in the different gamete functions has only been documented partially. In this
      study we have examined the progression of mouse spermatozoa through the oocyte
      investments in order to determine which steps require glucose. Evidence is
      presented of glucose involvement during this sequence of events, since in-vitro
      fertilization was inhibited in glucose-free medium even when spermatozoa were
      capacitated in the presence of glucose. Access to the zona pellucida was not
      inhibited in the absence of glucose, suggesting that capacitation, progressive
      motility and zona binding of spermatozoa do not depend on the presence of an
      extracellular glycolysable substrate. However, zona penetration was prevented in
      the absence of glucose. Most importantly, the zona pellucida-induced acrosome
      reaction was found to occur in glucose-free medium. It is proposed that
      hyperactivated motility, which has been described to require glucose in the
      literature, may be the precise process responsible for the failure of spermatozoa
      to enter the perivitelline space.

PMID- 8737040
TI  - In-vitro initiation of forward motility in testicular spermatozoa.
AB  - Initiation of forward motility in vitro was investigated in goat and ram
      spermatozoa obtained from the rete testis. No forward motility was generated in
      the immotile testicular spermatozoa when they were incubated in a modified
      Ringer's solution containing theophylline (30 mM) and epididymal plasma (2 mg
      protein/ml). However, these reagents induced non-progressive flagellar movement
      in approximately 25% of spermatozoa. Bicarbonate (25 mM) induced forward motility
      in approximately 16% of the goat/ram testicular spermatozoa. Theophylline was
      essential for the bicarbonate-mediated activation of sperm motility, but
      epididymal plasma had no significant effect on this activation process.
      Theophylline activated progressive motility in testicular spermatozoa in a dose
      dependent manner, the maximum effect occurring after incubation for 10 min with
      30 mM theophylline. The initiation profile of in-vitro motility of goat/ram
      spermatozoa from the caput epididymis closely resembled that of testicular
      spermatozoa except that induction of motility in the caput spermatozoa was
      dependent both on bicarbonate and epididymal plasma. The data indicate that,
      unlike caput epididymal spermatozoa, initiation of motility in testicular
      spermatozoa is not dependent on motility-promoting protein(s) in epididymal
      plasma.

PMID- 8737041
TI  - Are the characteristics of spermatozoa in the insemination medium useful for
      predicting in-vitro fertilization results?
AB  - To determine whether the characteristics of Percoll-selected spermatozoa are more
      predictive of in-vitro fertilization (IVF) results than are those of native
      semen, 118 semen samples from patients undergoing an IVF attempt were studied.
      Motility, using computer-assisted sperm analysis, and morphology were recorded
      before and after sperm selection on a Percoll gradient. Percoll selection
      increased the percentage of morphologically normal spermatozoa (58.2 +/- 19.9%
      versus 47.9 +/- 17.9%; p < 0.0001). This increase concerned almost all
      abnormalities and especially abnormalities of the midpiece (cytoplasmic droplets
      and bent tails). However, morphology of spermatozoa in the Percoll fraction had
      the same predictive value for IVF as did that for whole semen. Concerning
      motility, all parameters, except linearity, were improved by Percoll preparation,
      and their predictive value for IVF results was significantly higher in the
      Percoll fraction than in native semen. Therefore, it is concluded that, even if
      sperm characteristics are improved dramatically after Percoll selection, only
      motility analysis then gave more practical information than did analysis of sperm
      characteristics in native semen. This suggests that impairment of spermiogenesis,
      which presumably induces sperm abnormalities, is more important than are the
      actual characteristics of the spermatozoa.

PMID- 8737042
TI  - Detection of Chlamydia trachomatis in the prostate by in-situ hybridization and
      by transmission electron microscopy.
AB  - Chlamydia trachomatis infection has been investigated in the prostate gland using
      in-situ DNA hybridization and transmission electron microscopy. Sixty-four
      samples of tissue removed by trans-urethral resection or by open surgery from men
      with benign prostatic hypertrophy (BPH), were examined histologically and 20 of
      the cases were found to be positive for mononuclear cell infiltration. Some
      samples were then investigated using in-situ hybridization and transmission
      electron microscopy. Out of 20 tissue samples with mononuclear cell infiltration,
      nine were found to be positive for C. trachomatis infection.

PMID- 8737043
TI  - Maturation of sperm motility in the epididymis of the common marmoset (Callithrix
      jacchus) and the cynomolgus monkey (Macaca fascicularis).
AB  - The acquisition by spermatozoa of the capacity for movement upon liberation from
      the epididymal duct into buffer is one of the obvious changes associated with
      sperm maturation and, hence, studies of sperm kinematics might provide good
      indices for sperm maturation. Profiles of development in the movement pattern of
      spermatozoa taken from six regions of the epididymis were established in marmoset
      and cynomolgus monkeys using computer-assisted sperm analysis. Motion of
      spermatozoa from initial regions was sluggish and irregular, then developed in
      the more distal region into erratic movement effected by an increase in the
      vigour of flagellation as reflected by curvilinear velocity. The tendency of
      immature spermatozoa to display circular motion was more common in the marmoset
      than in the cynomolgus monkey. In the marmoset the most drastic changes in
      percentage motility and kinematic parameters of spermatozoa occurred between the
      distal caput and the proximal corpus; maximal values for these parameters were
      found around the distal corpus epididymis. For the cynomolgus spermatozoa the
      sharpest gain in percentage motility was also achieved between the caput and
      proximal corpus epididymis, but with full kinematic development in the proximal
      cauda epididymis. These maturational changes were not synchronous among
      spermatozoa from the same site as they moved along the epididymis, as reflected
      in the heterogeneity of each sample in the kinematic properties of individual
      spermatozoa, especially those from the proximal corpus epididymis. The
      maturational profiles in the monkeys are comparable to the situation in the
      human, for which they may provide a useful model.

PMID- 8737044
TI  - Immunohistochemical detection of immature Sertoli cell markers in testicular
      tissue of infertile adult men: a preliminary study.
AB  - Testicular biopsy specimens from oligozoospermic infertile patients are
      characterized by different types of spermatogenic impairment in adjacent
      seminiferous tubules, a phenomenon called mixed atrophy. In order to evaluate
      possible involvement of the state of Sertoli cell differentiation, the
      distribution pattern of anti-Mullerian hormone (AMH), vimentin and cytokeratin
      intermediate filament proteins was investigated by means of immunohistochemistry.
      AMH immunoactivity occurs in Sertoli cells of the normal postnatal prepubertal
      testis, but it is absent in the adult testis with normal spermatogenesis. In the
      case of mixed atrophy, AMH immunoactivity was found in Sertoli cells of tubules
      showing spermatogenic arrest at the level of spermatogonia and in tubules showing
      Sertoli-cell-only (SCO) syndrome. Vimentin was expressed regularly in Sertoli
      cells independent of spermatogenic impairment or the state of Sertoli cell
      differentiation. Cytokeratin immunoactivity occurs in Sertoli cells of the normal
      postnatal prepubertal testis. Furthermore, cytokeratin expression was found in
      Sertoli cells of tubules showing spermatogenic arrest at the level of
      spermatogonia and in some SCO tubules. Co-expression of AMH and cytokeratin
      suggests that spermatogenic impairment such as spermatogenic arrest and SCO
      syndrome in human seminiferous tubules is associated with a population of Sertoli
      cells showing a prepubertal stage of development. The different pattern of AMH
      and cytokeratin expression in SCO tubules indicates that Sertoli cells in SCO
      syndrome show a mosaic pattern of differentiation.

PMID- 8737045
TI  - hP, the component of log P controlling structure-activity relationships amongst
      non-steroidal anti-inflammatory drugs.
AB  - A range of 25 drugs and other compounds selected from published sources by strict
      criteria, has been used to confirm that their ability to inhibit the production
      of prostaglandin by mouse peritoneal macrophage does not correlate with log P but
      with hP, the parameter composed of only the hydrophobic contributions (atoms and
      groups composed of carbon, hydrogen and halogens). Other heteroatoms and physical
      properties can usually be ignored. Anti-inflammatory activity does not depend
      upon pKa or partition phenomena unless extreme, nor does it depend primarily upon
      the structural types within the range phenols, salicylic acids, mefenamic acids,
      areneacetic and profenic acids.

PMID- 8737046
TI  - Correlation of pharmacological properties of a group of hypolipaemic drugs by
      molecular topology.
AB  - This investigation was undertaken to test the ability of the molecular
      connectivity model to predict the percentage of plasma protein binding, the
      percentage of total cholesterol reduction and oral LD50 in rats of a group of
      hypolipaemic drugs using multi-variable regression equations with multiple
      correlation coefficients, standard error of estimate, degrees of freedom, F
      Snedecor function values, Mallow's CP and Student's t-test as criteria of fit.
      Regression analyses showed that the molecular connectivity model predicts these
      properties. Corresponding stability (cross validation) studies were made on the
      selected prediction models which confirmed their goodness of fit. The results
      also demonstrated that the presence of substituents and molecular volume,
      determine the value of these properties in hypolipaemic drugs.

PMID- 8737047
TI  - Structure-activity relationships of some novel coronary dilator derivatives of
      palmitoyl carnitine in the rat isolated heart.
AB  - The structure-activity relationships of some novel coronary dilator derivatives
      of palmitoyl carnitine in the rat isolated perfused heart are described. It has
      been shown previously that esterification of palmitoyl carnitine changes the
      activity of the compound from a coronary constrictor to a coronary dilator. In
      this study, it was found that the ester group is not a necessary requirement for
      coronary dilator activity, but only the absence of the negatively charged
      carboxylic acid group of palmitoyl carnitine, as compounds containing an ethyl
      group in place of the ester group were also active coronary dilators.
      Furthermore, substituting the methyl groups attached to the nitrogen atom of the
      molecule profoundly altered coronary dilator activity. A quaternary ammonium
      group was a necessary requirement for potent coronary dilator activity.

PMID- 8737048
TI  - Studies on powder plug formation using a simulated capsule filling machine.
AB  - Using an apparatus which simulates the action of a Macofar 13-2 dosating-type
      capsule-filling machine, the variation in plug weight and density with changing
      machine parameters has been studied. The piston ejection speed has no effect on
      plug properties. However increase in compression speed leads to a less
      consolidated powder plug and hence reduced plug weight. Application of higher
      pressures reduces plug weight changes, but would be expected to affect release
      characteristics. Comparison of axial and radial pressures generated by plugs of
      Starch 1500 and lubricated lactose show significant differences which can be
      explained by the different consolidation and elastic properties of the two
      solids.

PMID- 8737049
TI  - The effects of backing materials and multilayered systems on the characteristics
      of bioadhesive buccal patches.
AB  - The effects of backing materials (ethylcellulose, polyvinylpyrrolidone and
      cellulose acetate mixture, and poly(ethylene-co-vinyl acetate) on the
      characteristics (hydration and adhesion) of newly developed bioadhesive patches
      for controlled drug delivery via the buccal mucosa were investigated. It was
      found that the swelling profiles of buccal patches were changed dramatically by
      the species and amount of the backing materials, and those changes could alter
      the drug release profile. The drug release profiles of single-layered and
      multilayered buccal patches were significantly different. It was demonstrated
      that the multiple-layer device could be used to modify the drug release for
      obtaining the ideal clinical pharmacokinetic release profile.

PMID- 8737050
TI  - Poly-(D,L-lactic acid) microspheres incorporating histological dyes for intra
      pulmonary histopathological investigations.
AB  - Polylactic acid (PLA) microspheres incorporating fluorescein as a histological
      marker have been prepared and used as a model for the testing of inhaled PLA
      microspheres (2-5 microns) in the lung. PLA microspheres (20 mg) were delivered
      to rabbits in the form of a saline nebulization. The distribution pattern within
      the pulmonary system showed that the fluorescein-labelled microspheres were
      distributed about the four lobes in discrete groups. The comparative numbers of
      these groups showed a trend towards a reduced concentration in the lower lobes.
      Subsequent histological examination revealed that the microsphere-treated lungs
      had been significantly damaged after 24 h. Histological damage was assessed in
      terms of pulmonary haemorrhage, eosinophilia and neutrophil infiltration.

PMID- 8737051
TI  - Modified beta-cyclodextrin (SBE7-beta-CyD) with viscous vehicle improves the
      ocular delivery and tolerability of pilocarpine prodrug in rabbits.
AB  - The complexation of pilocarpine prodrug, O,O'-dipropionyl-(1,4-xylylene)
      bispilocarpate, with various beta-cyclodextrin (beta-CyD) derivatives was studied
      by the phase solubility method. The effects of coadministered sulphobutyl ether
      beta-CyD (SBE7-beta-CyD) with and without poly(vinyl alcohol) (PVA) on the miotic
      response and eye irritation of the prodrug were investigated in pigmented
      rabbits. The pilocarpine prodrug formed 1:1 inclusion complexes with variably
      substituted sulphobutyl ether derivatives of beta-CyD (SBE4-beta-CyD and SBE7
      beta-CyD), and 1:1 and 1:2 complexes with hydroxypropyl-beta-CyD (HP-beta-CyD) at
      pH 7-4. Coadministered SBE7-beta-CyD eliminated the eye irritation due to the
      pilocarpine prodrug, but also decreased the miotic response. Ocular absorption of
      the prodrug was improved by increasing the viscosity of prodrug/SBE7-beta-CyD
      solution with PVA without inducing any eye irritation. Eye irritation due to
      viscous prodrug/SBE7-beta-CyD solutions was comparable with isotonic NaCl
      solution. We conclude that administration of pilocarpine prodrug in viscous SBE7
      beta-CyD solution decreases substantially eye irritation while ocular absorption
      is not affected.

PMID- 8737052
TI  - Intestinal absorption studies on peptide mimetic alpha-methyldopa prodrugs.
AB  - Two dipeptide mimetic prodrugs, 1 and 2, and two tripeptide mimetic prodrugs, 3
      and 4, of L-alpha-methyldopa were evaluated for intestinal absorption by in-situ
      single pass rat jejunal perfusion studies and by in-vitro uptake experiments in
      brush-border membrane vesicles (BBMVs) prepared from rat intestine. In the
      perfusion studies, compound 1 demonstrated a 3.5-fold increase in permeability
      (Pm* = 2.27) as compared with that of alpha-methyldopa (Pm* = 0.65), indicating
      that this prodrug was better absorbed in the intestine than its parent drug.
      Other prodrugs showed no significant improvement in intestinal permeability. The
      results correlated with the results of BBMV uptake studies. In the presence of an
      inward proton gradient, compound 1 showed Michaelis-Menton saturable kinetics of
      BBMV uptake with a low value of K(m) (0.06 +/- 0.13 mM) and a high value of
      Vmax/K(m)(36.38 nmol (mg protein)-1/30s mM-1) at a low concentration range and a
      linear uptake at high concentrations with Kd = 0.14 +/- 0.02 mM. Compounds 2 and
      3 were mainly taken up in BBMVs via passive diffusion. Compound 4 was taken up in
      BBMVs basically via the carrier-mediated transport system, while the rate of
      uptake was much lower than that of compound 1. The uptake of compounds 1 and 4
      was significantly inhibited by dipeptides L-Gly-L-Pro and L-Gly-L-Phe, and
      cephradine, a beta-lactam known to be transported via the dipeptide carrier
      system, indicating that both compounds were taken up in BBMVs via the H(+)
      coupled dipeptide-mediated transport system. In contrast to the complicated
      uptake profile of alpha-methyldopa, the higher rate of BBMV uptake with less
      variation demonstrated on compound 1 suggested that the attached nonessential
      amino acid moiety, D-phenylglycine, is a feasible delivery tool in carrying the
      parent drug through the intestine.

PMID- 8737053
TI  - Uptake and transport characteristics of chloroquine in an in-vitro cell culture
      system of the intestinal mucosa, Caco-2.
AB  - The transepithelial transport and uptake of chloroquine were studied in cultured
      human intestinal Caco-2 cell layers, to investigate whether a specific mechanism
      facilitates the flux of chloroquine. Due to ionization of chloroquine at the pH
      of the intestinal lumen, the fraction of the neutral form, which is required for
      partitioning into biological membranes, is very low, while oral bioavailability
      has been reported to be nearly complete. Several observations, such as
      concentration-dependent uptake and temperature-dependent transepithelial flux,
      suggest the presence of carrier mediated transport. However, alternative
      mechanisms may be invoked to explain these observations. It is suggested that
      concentration dependence can originate from ion-trapping in acidic compartments
      of the cell or non-specific binding to cell components, while temperature
      dependent transport can, at least partly, be explained by the temperature
      dependence of the acid dissociation constants of chloroquine. No differences were
      observed in the transepithelial flux of the enantiomers of chloroquine. pH
      dependent uptake as well as pH-dependent transepithelial transport suggest that
      the translocation of chloroquine occurs according to the fraction of neutral
      molecules. From the data obtained in this study, it is concluded that chloroquine
      crosses the gastrointestinal barrier by passive diffusion. The extensive area of
      the gastrointestinal tract probably compensates for the low fraction of the
      neutral molecule. An interesting finding of this study was the concentration
      dependent increase in transepithelial electrical resistance across monolayers
      incubated with chloroquine at the apical side.

PMID- 8737054
TI  - Influence of plasma-protein binding on analgesic effect of methadone in rats with
      spontaneous withdrawal.
AB  - The effect of spontaneous withdrawal on alpha 1-acid glycoprotein (AAG) levels
      and methadone protein binding has been studied in the rat. Animals were made
      physically dependent on morphine by providing morphine HCl in drinking water for
      three weeks. The natural opiate withdrawal was induced in rats by substituting
      the morphine solution with drinking water. The severity of the abstinence
      syndrome was assessed at various time intervals. After 12 h of withdrawal, the
      animals showing abstinence signs and low morphine levels were injected with
      intravenous methadone (0.35 mg kg-1) and the analgesic effect was measured by the
      tail-flick method and compared with animals receiving water. The oral
      administration of morphine produced an increase in AAG levels from 0.64 +/- 0.05
      g L-1 in control animals to 1.47 +/- 0.92 g L-1 in experimental animals at the
      point of withdrawal and 1.21 +/- 0.09 g L-1 24 h after withdrawal. The percentage
      of methadone unbound was significantly lower in morphine-treated than in control
      animals. A significant correlation between AAG levels and percentage of methadone
      bound was observed. A parallel analgesic effect after intravenous methadone, as
      measured by AUC in the tail-flick test, was less in abstinence animals than in
      control (287.6 +/- 24.8 compared with 401.0 +/- 37.06s min). We suggest that in
      the withdrawal syndrome an adjustment of methadone dose may be necessary because
      of changes in protein binding.

PMID- 8737055
TI  - Pharmacological characterization of the vanilloid receptor in the rat isolated
      vas deferens.
AB  - The present study set out to further characterize the vanilloid receptor in the
      rat isolated vas deferens. In this preparation, both capsaicin and
      resiniferatoxin (RTX) evoked a concentration-dependent inhibition in the
      amplitude of electrically-evoked contractions with pEC50 values of 7.62 +/- 0.03
      and 12.2 +/- 0.21 respectively. Responses to capsaicin were fast in onset and
      faded rapidly over a 30-min exposure period, whereas those to RTX were slow in
      onset and well maintained, an observation believed to reflect pharmacokinetic
      differences in the rate of penetration to the vanilloid receptor. Responses to
      both agonists showed mutual cross-desensitization and were antagonized by both
      the vanilloid-receptor antagonist capsazepine and the ion-channel blocker
      ruthenium red. The capsaicin analogue, olvanil failed to either mimic or
      antagonize capsaicin-evoked responses in the rat isolated vas deferens, an effect
      at variance with previous observations in other tissues. The reason for these
      differences is unclear, but the possibility of multiple classes of receptor
      cannot at this stage be ruled out.

PMID- 8737056
TI  - Effects of sulpiride and nemonapride, benzamide derivatives having distinct
      potencies of antagonistic action on dopamine D2 receptors, on sensitization to
      methamphetamine in mice.
AB  - The acute ambulatory stimulation by methamphetamine (2 mg kg-1 S.C.) was dose
      dependently reduced by 3-h pretreatment or combined treatment with sulpiride (1
      100 mg kg-1 S.C.), and combined treatment with nemonapride (0.003-0.03 mg kg-1
      S.C.), benzamide derivatives having selective antagonistic action on dopamine D2
      receptors. The repeated (5 times) administrations of methamphetamine at 3-day
      intervals induced a sensitization to its ambulation-increasing effect, and the
      sensitization was significantly inhibited by 3-h pretreatment with either
      sulpiride (10-100 mg kg-1), or combined treatment with either sulpiride (3 or 10
      mg kg-1) or nemonapride (0.01 or 0.03 mg kg-1) at each methamphetamine
      administration. Although the ambulation-increasing effect of methamphetamine
      disappeared by 3 h after the administration, the 3-h post-treatment with
      sulpiride (3 mg kg-1) or nemonapride (0.03 mg kg-1) after each methamphetamine
      administration was effective for a significant inhibition of the induction of
      methamphetamine sensitization, whereas, the comparatively higher doses of
      sulpiride (30 and 100 mg kg-1 in the combined treatment, and 10-100 mg kg-1 in
      the post-treatment) did not inhibit the methamphetamine sensitization. On the
      other hand, the repeated administrations of sulpiride (30 and 100 mg kg-1) alone,
      but not any doses of nemonapride, at 3-day intervals elicited a significant
      increase in the sensitivity to methamphetamine. These results suggest that,
      although the potencies of the anti-methamphetamine effects of sulpiride and
      nemonapride differ by a factor of 3000, they inhibit the induction of
      sensitization to methamphetamine in the pretreatment, combined treatment and
      early post-treatment schedules. However, it is also suggested that the repeated
      treatment with comparatively higher doses of sulpiride may produce a denervation
      supersensitivity of dopamine D2 receptors, and resultant increase in the
      sensitivity to methamphetamine.

PMID- 8737057
TI  - Synthesis, gastroprotective, antisecretory and anti-Helicobacter effect of N-[3
      (3-(1-piperidinylmethyl) phenoxy)propyl]-hydroxyacetamide 2-hydroxypropane-1,2,3
      tricarboxylate bismuth (3+) complex (MX1)-MX1.
AB  - MX1 (N-[3-(3-(1-piperidinylmethyl)phenoxy)propyl]-hydroxyacetamide+ ++ 2
      hydroxypropane-1,2,3-tricarboxylate bismuth (3+) complex) is a novel salt of the
      active metabolite of H2-antagonist roxatidine with a complex of bismuth with
      citric acid. In a model of ethanol-induced ulcers in male Wistar rats, both
      roxatidine and the bismuth salt reduced the number and the total length of
      lesions. Comparison of roxatidine and MX1 at equimolar doses of 160 mumol kg-1
      showed a more potent cytoprotective effect of MX1. The potency of anti-secretory
      and antiacidic effects of MX1 was more than twice that of roxatidine on histamine
      stimulated secretion in female Wistar pylorus-ligated rats. Microbiological tests
      with the reference bismuth preparation De-Nol showed prominent anti-Helicobacter
      properties of MX1 in-vitro. Both test compounds had similar range of MICs to
      Helicobacter pylori, from 4 to 64 microgram bismuth mL-1. The cytoprotective,
      antisecretory, anti-acidic and anti-Helicobacter properties of the new agent MX1
      warrant further more extensive pharmacological and clinical trials.

PMID- 8737058
TI  - Changes in the subcellular distribution of the rat uterus oestrogen receptor as
      induced by oestradiol, tamoxifen and ZD 182,780.
AB  - The aim of this work was to compare the subcellular distribution of the oestrogen
      receptor from the uteri of rats treated with vehicle alone (control group),
      oestradiol or one of the anti-oestrogenic drugs tamoxifen and ZD 182,780. The
      nuclear, microsomal and cytosolic oestrogen receptor contents were evaluated by
      an immunoenzymatic method ("ER-EIA" kit from Abbott Laboratories) and the results
      in each fraction were expressed as a percentage of the total number of receptors.
      Parallel studies were performed to assess the uterotrophic effect of these drugs
      and to assess that they had reached the uterus. In the control group, we found
      that the oestrogen receptor was distributed mainly between the microsomal (29.1
      +/- 1.3%) and cytosolic (68.1 +/- 0.9%) fractions, with only a small amount
      located in the nucleus (2.8 +/- 0.5%). When oestradiol was administered, the
      oestrogen receptor distribution was: nuclear 11.7 +/- 2.0, microsomal 15.5 +/-
      1.3 and cytosolic 72.8 +/- 3.3% and, in the tamoxifen group, the results were:
      nuclear 18.5 +/- 1.5, microsomal 26.0 +/- 3.1 and cytosolic 55.5 +/- 3.4%, which
      shows a relative shift both to the control and the oestradiol-treated groups. In
      the uteri of rats treated with ZD 182,780 the results were very similar to those
      obtained in the control group. Our results indicate that the subcellular
      distribution of the oestrogen receptor varies according to the drug administered
      and that this receptor may not be located in a single subcellular compartment.
      Moreover, the nuclear uptake of the ZD 182,780-oestrogen receptor complex seems
      to be blocked, possibly due to impaired receptor dimerization. In the case of
      tamoxifen, the intracellular transport of the receptor also seems to be blocked,
      probably due to the nuclear retention of the receptor, thus suggesting that
      tamoxifen must impair the oestrogen receptor function on a step subsequent to the
      receptor dimerization.

PMID- 8737059
TI  - Effect of policosanol on foam-cell formation in carrageenan-induced granulomas in
      rats.
AB  - Policosanol is a new cholesterol-lowering drug isolated and purified from sugar
      cane wax, which prevents the development of lipofundin-induced lesions and foam
      cell formation in New Zealand rabbits and Wistar rats. This study was conducted
      to examine the effects of policosanol on foam-cell formation in carrageenan
      induced granulomas in rats. Eighteen Wistar rats were randomly distributed in
      three experimental groups which received orally for 20 days Tween 20 H2O as
      vehicle (control group) or policosanol at 2.5 or 25 mg kg-1. At the 11th day,
      lipofundin was injected intraperitoneally for 8 days to induce formation of foam
      cells in the granuloma. At day 13, carrageenan was injected subcutaneously for
      granuloma induction and seven days later animals were killed. A significant
      reduction of the foam-cell formation in granulomas of policosanol-treated rats
      was observed. It is concluded that policosanol prevents the development of foam
      cells in carrageenan-induced granulomas (extravascular medium) in rats.

PMID- 8737060
TI  - A novel method for the preclinical assessment of rectal irritation.
AB  - The purpose of this study concerns a novel method for preclinical assessment of
      rectal irritation caused by suppositories introduced into the rectum. Rectal
      irritation was assessed by the balloon method in fasting conscious rats. This
      method is based on measuring rectal contractions due to possible irritation
      caused by the presence of drugs and adjuvants in the suppository. In control
      experiments (vehicle only), significant rectal contractions were not observed in
      a range of pH 1.5-11.0 and osmotic pressure 70-2000 mOsm kg-1 H2O, respectively.
      On the other hand, strong contractions were observed after rectal administration
      of an aqueous solution of 50% glycerin, 100 mM sodium caprate or 25 mM sodium
      cholate. The intensity of contraction after rectal administration of sodium
      caprate or sodium cholate was dependent on the concentration in the dosing
      solution. In addition, the effect of sodium caprate and sodium cholate on rat
      rectal mucosa was investigated by optical light microscopy. Although slight or
      moderate alteration such as the presence of mucinous substance in lumen and
      congestion, oedema and haemorrhage of the rectal membrane 20 min after rectal
      administration, there was no major damage to the rectal mucosa. There was a
      correlation between the median score for mucinous substance in lumen and mean
      intensity of rectal contraction. For comparative purposes, defecating sensations,
      pain, itch, burning sensations, and awareness of the presence of a foreign body
      after administration of suppositories containing 0, 1, 2 and 4% sodium caprate
      were examined in eight healthy volunteers. The defecating sensation in the human
      subjects correlated with the intensity of rectal contraction in rats. The results
      suggest that rectal contraction in conscious rats could be a useful index for
      prediction of a defecating sensation in man.

PMID- 8737061
TI  - Surprising pharmacological activity of analogues designed by substitution of
      position 3 in arginine vasopressin (AVP) and 8-D-arginine vasopressin with L-2
      napthylalanine.
AB  - In an attempt to develop more active and selective analogues of arginine
      vasopressin (AVP), two peptides have been designed, synthesized and tested for
      vasopressor (V1-receptors) and antidiuretic (V2-receptors) activities. We also
      estimated the uterotonic and anti-uterotonic activities of these compounds in
      vitro. The first peptide, [(L-2-Nal)3] AVP is a highly active V2-agonist. The
      second analogue, [(L-2-Nal)3, (D-Arg)R]VP is among the most potent antagonists of
      the vasopressor response to AVP. Moreover, it is the first V1-antagonist devoid
      of anti-uterotonic activity. High antipressor potency of the second peptide was
      achieved without modification of position 1.

PMID- 8737062
TI  - Glibenclamide antagonizes the inhibitory effect of morphine on gall bladder
      emptying.
AB  - Egg yolk-induced gall-bladder emptying in mice was used to investigate the effect
      of glibenclamide and minoxidil (ATP-dependent K(+)-channel modulators) on biliary
      tract effects of morphine. The inhibitory effect of morphine (1-4 mg kg-1, i.p.)
      on egg yolk-induced gall-bladder emptying was completely blocked by pretreatment
      with naloxone (2 mg kg-1, i.p.) or glibenclamide (0.65 mg kg-1, i.p.) whereas,
      pretreatment with minoxidil (0.65 mg kg-1, i.p.) did not modify the inhibitory
      effect of morphine on gall-bladder emptying. Our results suggest that biliary
      tract actions of morphine are mediated through glibenclamide-sensitive K+
      channels similar to those involved in the analgesic action of morphine.

PMID- 8737063
TI  - Antihypertensive drugs reduce noradrenaline-induced hypertrophy of cultured
      myocardial cells.
AB  - The cellular mechanisms of cardiac hypertrophy are still largely unknown. In-vivo
      studies have demonstrated that antihypertensive drugs can regress hypertrophy
      independently of reductions in blood pressure. The antihypertrophic effects of
      metoprolol, propranolol, felodipine, verapamil and captopril were studied in
      neonatal cardiac myocyte culture. Prazosin was used as a positive control.
      Hypertrophy was defined as an increase in protein content measured by [3H]leucine
      incorporation. Noradrenaline induced a 1.5-fold increase in protein synthesis
      over 48 h. Prazosin prevented the hypertrophic effect of noradrenaline.
      Adrenergic beta-receptor blocking agents and calcium antagonists reduced myocyte
      hypertrophy in a dose-dependent manner. The angiotensin-converting enzyme
      inhibitor captopril was ineffective. These results indicate that adrenergic beta
      receptor blockers and calcium antagonists may have direct nonhaemodynamic effects
      on the growth of cultured cardiac myocytes.

PMID- 8737064
TI  - Preventive effects of unsei-in and oren-gedoku-to, Chinese traditional medicines,
      against rat paw oedema and abdominal constriction in mice.
AB  - Oren-gedoku-to and Unsei-in are complex mixtures of ingredients derived from
      plants. These two drugs are clinically most frequently used in the treatment of
      Behcet's disease, we have investigated the anti-inflammatory and analgesic
      actions of Oren-gedoku-to and Unsei-in using a battery of tests; rat paw oedema
      induced by five different agents; abdominal constriction; mouse ear swelling; and
      dye leakage tests, designed to clarify the therapeutic potential of these
      medicines. The findings in this study that these medicines are able to inhibit
      the rat paw oedema, suppress the abdominal constriction and inhibit the increased
      dye permeability confirm the analgesic and anti-inflammatory effects of these
      compounds. From these results there seems a clear rationale for exploring the
      effectiveness of these Chinese medicines in the treatment of chronic and acute
      inflammatory diseases.

PMID- 8737065
TI  - Modification of Ca2+ metabolism in the rabbit aorta as a mechanism of spasmolytic
      action of warifteine, a bisbenzylisoquinoline alkaloid isolated from the leaves
      of Cissampelos sympodialis Eichl. (Menispermaceae).
AB  - The regulation of intracellular Ca2+ as a mechanism of spasmolytic activity of a
      bisbenzylisoquinoline alkaloid, warifteine, isolated from the leaves of
      Cissampelos sympodialis, Eichl (Menispermaceae) was studied in the rabbit aorta.
      Warifteine (pD2' 4.12 +/- 0.09) similar to verapamil (pD2' 6.89 +/- 0.05)
      antagonized, in a noncompetitive and reversible manner, KCl-induced contractions,
      mediated by Ca2+ entry through voltage-operated channels. Noradrenaline-induced
      sustained contractions mediated by Ca2+ entry through receptor-operated channels
      were also inhibited by warifteine (IC50 6.03 x 10(-5) M) and the standard agent
      sodium nitroprusside (IC50 1.9 x 10(-8) M). In Ca(2+)-free medium, the alkaloid
      reduced the intracellular Ca(2+)-dependent transient contraction to noradrenaline
      by inhibiting the release of Ca2+ (IC50 2.6 x 10(-5) M) from the stores and the
      refilling (IC50 1.9 x 10(-5) M) of the intracellular stores. The standard agent,
      procaine, also inhibited the release of Ca2+ (IC50 3.2 x 10(-5) M) but had no
      significant effect on Ca2+ uptake into the stores. Warifteine failed to affect
      intracellular Ca2+ stores sensitive to caffeine, while procaine inhibited (IC50
      7.9 x 10(-4) M) the release of Ca2+ from these stores. The results indicate that
      warifteine may cause muscle relaxation by inhibiting Ca2+ channels and by
      modifying the intracellular Ca2+ stores sensitive to noradrenaline.

PMID- 8737066
TI  - Perimetric [Ca2+]i rise and exocytosis detected by ultraviolet laser scanning
      confocal microscopy in rat peritoneal mast cells.
AB  - It has been reported that in dialysed mast cells an increase in mean [Ca2+]i is
      neither necessary nor sufficient for secretion; however, it is possible that
      juxtamembranal [Ca2+]i may exceed the mean [Ca2+]i before exocytosis. The present
      study was carried out to analyse spatial and temporal dynamics of [Ca2+]i and
      concomitant exocytosis in intact rat peritoneal mast cells using UV laser
      scanning confocal microscopy. Stimulation with Compound 48/80 (16 microM)
      increased mean [Ca2+]i, causing an initial rapid elevation from 40 to 200 nM,
      which lasted for 6 s and was followed by a delayed secondary increase to 600 nM.
      Exocytotic images were seen in the cell perimeter 16 s after the stimulation.
      Perimetric and nuclear [Ca2+]i increased to several mumoles per litre, while that
      in the intermediate region remained low. In a Ca(2+)-deficient environment,
      Compound 48/80 still increased perimetric [Ca2+]i to micromolar values and
      induced exocytosis. This study clearly indicates, for the first time, that a
      perimetric increase in [Ca2+]i to micromolar levels precedes exocytosis, in
      intact, as opposed to permeabilized cells.

PMID- 8737067
TI  - The induction of c-fos and c-jun in the stretched latissimus dorsi muscle of the
      rabbit: responses to duration, degree and re-application of the stretch stimulus.
AB  - The mRNA levels of the proto-oncogenes c-fos and c-jun were measured in the
      rabbit latissimus dorsi (LD) muscle in response to the application of various
      stretch regimes in vivo. It was shown that it was necessary for the stretch to be
      applied continuously over 1 h in order to achieve full induction of c-fos and c
      jun mRNA at 1 h. In addition, a correlation was demonstrated between the degree
      of stretch imposed on the LD and the induced levels of c-fos and c-jun mRNA.
      Moreover, a second induction of these genes occurred when the LD was subjected to
      a second stretch stimulus. The magnitude and time course of the second response
      depended on the precise timing of the second stimulus in relation to the initial
      induction.

PMID- 8737068
TI  - Non-quantal acetylcholine release in the mouse diaphragm after phrenic nerve
      crush and during recovery.
AB  - The progressive decline and recovery of spontaneous quantal acetylcholine (ACh)
      release (miniature endplate potentials, MEPPs) and the H-effect were measured in
      the mouse diaphragm after nerve crush and during regeneration. The H-effect is
      the hyperpolarization of the muscle fibre membrane produced by the addition of
      (+)tubocurarine, which indicates non-quantal ACh release. One hour after nerve
      crush the H-effect had declined to 50% of control values and 4 h later the H
      effect disappeared completely. There were no substantial changes in the MEPP
      frequency and amplitude during the first 4 h after denervation. MEPP frequency
      then increased, but after 6 h of denervation it decreased and after 16 h no MEPPs
      were found in any of the muscle fibres. The times of onset of these denervation
      changes in the proximal, central and distal parts of diaphragm were similar.
      During reinnervation, the H-effect was detectable in all muscle parts 3 days
      before the reappearance of MEPPs. The H-effect developed first on day 8 in the
      proximal endplates and then, with a delay of 3 and 6 days, in the central and
      distal areas, respectively. During axonal regrowth the non-quantal release was
      restored before detectable quantal release. Non-quantal release is the first
      indication of the ability of the nerve terminal to release ACh in the process of
      reinnervation.

PMID- 8737069
TI  - Nitric oxide and release of the peptide VIP from parasympathetic terminals in the
      submandibular gland of the anaesthetized cat.
AB  - The role of nitric oxide (NO) in mediating various submandibular responses to
      stimulation of the parasympathetic innervation has been investigated in
      anaesthetized cats, in which N omega-nitro-L-arginine methyl ester (L-NAME; 30 mg
      kg-1 I.A.) was used to block the synthesis of NO. L-NAME significantly reduced
      the vasodilator response and the flow of saliva, together with the output of
      salivary protein that occurred during stimulation of the chorda lingual nerve (20
      Hz for 1 s at 10 s intervals), without significantly reducing the output of
      vasoactive intestinal peptide (VIP) from the gland. The results show that NO is
      implicated not only in the release of VIP, as established previously, but also in
      mediating its actions following release in the submandibular gland of the cat.

PMID- 8737070
TI  - Peroxidase and kallikrein in atropine-resistant secretion of submandibular saliva
      on parasympathetic nerve stimulation in anaesthetized rats.
AB  - Flow of submandibular saliva and the constituents secreted during chorda-lingual
      nerve stimulation at 40 Hz (3 x 10 min) were studied after alpha- and beta
      adrenergic blockade, and in the absence (control) or presence of cholinergic
      blockade in anaesthetized rats. Peroxidase and true tissue kallikrein (rK1) were
      assessed to gain insight into the effects of the non-adrenergic, non-cholinergic
      (NANC) transmitters on protein secretion by acini and granular tubules,
      respectively. From control glands there was an overall mean flow of 181 +/- 15
      microliters g-1 min-1, with no significant differences between the three periods.
      Secretion from atropinized glands was approximately 20% of that from control
      glands in the first 10 min, decreasing progressively to approximately 6% in the
      final period. Protein outputs from control glands showed no significant
      differences for the three periods (0.23 +/- 0.05 mg g-1 min-1). Protein outputs
      from atropinized glands were similar to controls in the first 10 min and then
      decreased significantly. Peroxidase output from control glands increased
      progressively (from 31 +/- 7 to 243 +/- 68 pmol dichlorofluorescein (DCF) g-1 min
      1) but in saliva from atropinized glands the overall mean output was only 4.5 +/-
      0.8 pmol DCF min-1 ml-1, with a progressive decrease between samples. Outputs of
      rK1 from control glands were similar for all samples (20.6 +/- 4.0 nmol AFC g-1
      min-1), but there was a significantly smaller and decreasing output of rK1 from
      atropinized glands. In conclusion, NANC transmitters released from
      parasympathetic nerves during stimulation at high frequency appear to have little
      influence on the secretion of protein from rat submandibular acini and granular
      tubule cells when acting in isolation. This contrasts with their effects on
      amylase secretion from rat parotid glands under similar circumstances.

PMID- 8737071
TI  - Characterization of a sodium-dependent magnesium efflux from magnesium-loaded rat
      pancreatic acinar cells.
AB  - This study investigates the mechanism of magnesium (Mg2+) transport (efflux) from
      the exocrine rat pancreas. Permeabilized pancreatic acini were loaded with Mg2+
      by employing a high-Mg2+ (12 mM) buffer containing A23187 (6 microM). Net Mg2+
      efflux was measured using the technique of atomic absorbance spectrophotometry.
      Incubation of preloaded acini in a buffer deficient in Mg2+ resulted in a large
      and time-dependent release of Mg2+ with maximal efflux occurring within 40 min.
      Pretreatment of loaded acini with bumetanide, SITS or ouabain had no significant
      effect on Mg2+ efflux. In contrast, when acini were pretreated with 10 mM
      dinitrophenol, 10(-4) M amiloride, 1 mM lidocaine or 1 mM quinidine there were
      significant (P < 0.001) decreases in net Mg2+ efflux. Replacement of
      extracellular sodium [Na+]o with either N-methyl-D-glucamine (NMDG), Tris or
      choline resulted in a significant (P < 0.001) inhibition of Mg2+ efflux. The
      results of this study indicate that Mg2+ transport (efflux) in pancreatic acinar
      cells may not be associated with the Na(+)-K(+)-ATPase, the Na(+)-K(+)-Cl-
      cotransporter or the anion exchanger, but with a Na(2+)-sensitive Mg2+ transport
      system.

PMID- 8737072
TI  - Cholecystokinin-8 and vasoactive intestinal polypeptide stimulate exocrine
      pancreatic secretion via duodenally mediated mechanisms in the conscious pig.
AB  - The effects of local and peripheral administration of cholecystokinin-8 (CCK-8)
      and vasoactive intestinal polypeptide (VIP) on basal pancreatic secretion were
      investigated in conscious pigs. Five pigs (20 +/- 2 kg, mean +/- S.E.M.) were
      chronically fitted with a T-shaped cannula in the duodenum, and catheters in the
      pancreatic duct, jugular vein, and right gastroepiploic artery. The arterial
      catheter was inserted against the bloodstream with its tip opposite the duodenal
      branch(es) of the right gastroepiploic artery, so that all injected peptides
      would reach the duodenal arterial circulation excluding the pancreas. Pancreatic
      secretion during basal conditions (i.e. after an overnight fast) exhibited a
      characteristic cyclic pattern (cycle duration, 70 +/- 4.2 min). Secretion volume
      oscillated between 0.2 +/- 0.04 and 4.0 +/- 0.9 ml kg-1 h-1 (P < 0.001), trypsin
      output between 9.6 +/- 1.9 and 29.1 +/- 4.1 U kg-1 h-1 (P < 0.001) and protein
      output between 0.36 +/- 0.08 and 9.2 +/- 1.7 mg kg-1 h-1 (P < 0.001). Infusion
      into the jugular vein for 1 min, during the trough of pancreatic secretion, of
      either CCK-8 (15 pmol kg-1 min-1) or VIP (7 pmol kg-1 min-1) did not stimulate
      pancreatic secretion. However, local infusion of an identical dose of CCK-8 or
      VIP into the duodenal arterial circulation increased the volume, protein output
      and trypsin output of the pancreatic juice (P < 0.05 to < 0.001). These results
      indicate that CCK-8 and VIP can stimulate the exocrine pancreas by a duodenally
      mediated mechanism.

PMID- 8737073
TI  - The effect of distension of the stomach on peripheral blood flow in anaesthetized
      pigs.
AB  - The present study was undertaken in anaesthetized pigs to determine the primary
      reflex effects of gastric distension on the peripheral circulation. Changes in
      blood flow in the splenic, superior mesenteric, left renal and left external
      iliac arteries were assessed using electromagnetic flowmeters during distension
      of a balloon in the stomach, performed at constant aortic blood pressure and
      heart rate, with 0.6 l of Ringer solution (mean gastric transmural pressure of
      about 12 mmHg). In fourteen pigs, a decrease in splenic, renal and iliac flows
      and variable changes in mesenteric flow were obtained. A decrease in mesenteric
      flow and more marked decreases in the other flows occurred in response to the
      distension after the administration of propranolol or butoxamine. In five pigs,
      the vasoconstrictive responses were graded by step increments in gastric
      distending volume from 0.4 to 0.8 l. The above responses were abolished by the
      administration of phentolamine (eight pigs) and by bilateral cervical vagotomy
      (six pigs). The results showed that innocuous distension of the stomach in
      anaesthetized pigs reflexly caused vasoconstriction in the splenic, renal and
      iliac vascular beds; vasoconstriction also occurred in the mesenteric vascular
      bed but only after beta-blockade. These reflex responses were mediated by
      sympathetic mechanisms which involved both alpha and beta vascular adrenoceptors
      and their afferent limb was in the vagal nerves.

PMID- 8737074
TI  - Reflex vascular responses from aortic arch, carotid sinus and coronary
      baroreceptors in the anaesthetized dog.
AB  - In chloralose-anaesthetized dogs, pressure applied to coronary, carotid and
      aortic baroreceptors were changed independently and the resulting reflex vascular
      responses were determined. Increases in pressure to each group of baroreceptors
      resulted in reflex vasodilatation; the maximal responses to distension of carotid
      and coronary baroreceptors were significantly larger than those to aortic
      receptors, but not different from each other. Increases in pressure in all three
      regions induced maximal responses at similar times from the onset of the pressure
      stimulus. However, the time for recovery of vascular resistance following a
      decrease in baroreceptor pressure differed. Vasoconstriction following a period
      of coronary hypertension occurred slowly, requiring 70 s for 90% of the response
      to develop. This was significantly longer than the corresponding times for
      carotid and aortic receptors (about 28 s). The rate of vasoconstriction in
      response to coronary baroreceptor unloading was influenced by the period for
      which the pressure stimulus was applied and vasoconstriction was even slower when
      the pressure stimulus had been maintained for 8 min. The mechanism responsible
      for delaying the vasoconstriction following a period of coronary hypertension is
      not known, but this effect may have important implications for the control of
      arterial blood pressure.

PMID- 8737075
TI  - Effects of moderate hypothermia on baroreflex and pulmonary chemoreflex heart
      rate response in decerebrate ferrets.
AB  - The effects on the baroreceptor reflexes and pulmonary reflexes of moderate
      immersion hypothermia (core temperature, 30.2 +/- 0.07 degrees C) have been
      investigated in the decerebrate ferret. Baroreflex sensitivity was estimated from
      the relationship between change in cardiac interval and change in systolic blood
      pressure following i.v. bolus injection of phenylephrine. The responses to
      phenylephrine in ferrets were best fitted by two linear slopes with an initial
      shallow slope, a, followed by a steeper slope, b. The slope or sensitivity of b
      was increased significantly by moderate cooling (n = 6 animals, 36 responses, P <
      0.05). Pulmonary J-receptor reflex sensitivity was assessed by i.v. injection of
      phenylbiguanide (PBG), which evokes a dose-dependent bradycardia. The bradycardic
      response was unaltered by the hypothermia (n = 6 animals, 88 responses).
      Electrical stimulation of the right peripheral vagal nerve was employed to assess
      effects on the efferent components of the reflexes. The bradycardia, in response
      to stimulation, was significantly increased by moderate cooling at all
      stimulation frequencies (n = 8 animals, 88 responses, P < 0.001). Thus the
      results suggested that baroreceptor heart rate reflex sensitivity was enhanced by
      the moderate hypothermia. At least one component of the enhanced baroreflex
      response may be the result of changes in the efferent pathway of the reflex
      response. However, the absence of effect of PBG may indicate a differential
      afferent and efferent organization of pulmonary J-receptors compared with
      baroreceptors.

PMID- 8737076
TI  - A dopamine transporter in human erythrocytes: modulation by insulin.
AB  - Red blood cells are capable of transport and accumulation of catecholamines. The
      aim of this paper is to characterize the catecholamine transport system in the
      human red blood cell and in particular that of dopamine. Dopamine, noradrenaline
      and adrenaline enter the red blood cell by a similar process, which shows
      saturation kinetics with Vmax values of 0.54 +/- 0.12, 0.48 +/- 0.08 and 0.63 +/-
      0.13 mumol (1 cells)-1 min-1, respectively, and K(m) values of 15.62 +/- 1.19,
      5.81 +/- 1.19 and 12.00 +/- 2.97 nM, respectively. Observations based on the
      dependence of dopamine influx on the transmembrane H+ gradient, and the effect of
      transport inhibitors such as DMA (dimethyl-amiloride), DIDS (4,4'
      diisothiocyanatostilbene 2,2'-disulphonic acid), reserpine, GBR 12909 (1-(2-(di(4
      fluoro-phenyl)-methoxy)-ethyl)-4-(3-phenylpropyl)piperazine) , GBR 12935 (1-(2
      (diphenyl-methoxy)-ethyl)-4-(3-phenyl-propyl)piperazine), and cyanine suggest
      that catecholamine transport is not mediated by the Na(+)-H+ exchanger, the anion
      exchanger or a system similar to that responsible for dopamine uptake in either
      synaptosomes or the proximal tubule. However, choline inhibits the influx of
      dopamine with an IC50 value of 17 microM and stimulates the efflux of dopamine
      with a K(m) value of 8.20 microM. These results strongly suggest that dopamine is
      transported by the choline exchanger previously reported to be present in red
      blood cells. Probenecid inhibits dopamine uptake with an IC50 of 0.63 microM. The
      presence of insulin receptors in human red blood cells, and the relationship
      between insulin and catecholamine levels in the plasma led us to investigate the
      effect of insulin on catecholamine transport. In fasting subjects, dopamine,
      adrenaline and noradrenaline influxes were higher than in fed subjects.
      Furthermore, the addition of exogenous insulin to red blood cells from fasting
      subjects significantly reduced the influx of catecholamines while no effect was
      observed when insulin was added to red blood cells obtained from fed subjects.
      The present study shows that catecholamines, and in particular dopamine, are
      transported in red blood cells via an exchanger which is possibly the choline
      transport system. The activity of this transporter is regulated by insulin. These
      results support a role for red blood cells as a storage pool for circulating
      catecholamines.

PMID- 8737077
TI  - Changes in the intracellular free amino acid pool in human saphenous vein tissue
      culture.
AB  - The aim of this work was to investigate the effect of tissue culture on the
      intracellular amino acid pool in both freshly isolated and surgically prepared
      saphenous vein segments taken from patients undergoing coronary artery bypass
      surgery (number of patients, n = 8). Viability of freshly isolated vein rings,
      indicated by ATP concentration, was maintained in culture (321 +/- 41 vs. 277 +/-
      31 nmol (g wet wt)-1, 0 vs. 14 days). The initial decrease in ATP concentration
      in surgically prepared rings was significantly reversed following 14 days in
      culture from 135 +/- 26 to 201 +/- 18 nmol (g wet wt)-1 (P < 0.05). Freshly
      isolated vein rings maintained their intracellular free amino acid pool during
      the 14 days in culture (from 166 +/- 25 to 166 +/- 23 mumol (g protein)-1).
      Surgical preparation of vein rings induced a decrease in the intracellular free
      amino acid pool (from 166 +/- 25 to 87 +/- 15 mumol (g protein)-1, P < 0.05).
      This decrease was partially reversed after 14 days in culture (140 +/- 19 mumol
      (g protein)-1). Although the total amino acid pool in both types of vein rings
      after 14 days in culture was similar, there were variations in individual amino
      acid concentrations. Freshly isolated rings showed an increase in glutamine
      concentration and a decrease in alanine and aspartate concentrations after 14
      days in culture. Surgically prepared vein rings showed a decrease in aspartate
      concentration and an increase in concentrations of glutamine, asparagine,
      glutamate and glycine. The changes in individual intracellular free amino acid
      concentrations, which were largely determined by the corresponding concentrations
      in the medium, indicates that culture media should be supplemented with taurine,
      aspartate and alanine.

PMID- 8737078
TI  - Cutaneous vascular control in the arms of women with postmastectomy oedema.
AB  - The control of forearm skin blood flow was examined in the swollen arms of twelve
      women with oedema caused by breast cancer treatment. The swollen arm was compared
      with the opposite unaffected (control) arm. Using laser Doppler flux (LDF) and
      continuous finger blood pressure (BP) measurements, vascular control was tested
      by applying a range of provocations previously shown to alter cutaneous vascular
      resistance (CVR) in healthy subjects. The tests and the accepted mechanism were:
      post-ischaemic hyperaemia (locally mediated vasodilatation), inspiratory gasp and
      cool reflex (both sympathetically mediated vasoconstriction), arm dependency
      (locally mediated vasoconstriction), and core heat load (sympathetically mediated
      vasodilatation). CVR was calculated as BP/(LDF-biological zero). Three
      differences between the control and swollen arms were identified. (i) The laser
      Doppler biological zero signal was significantly higher on the swollen side (P =
      0.005, Student's paired t test). (ii) Baseline LDF was significantly lower on the
      swollen side (P = 0.002), and apparent CVR correspondingly higher. (iii)
      Cumulative reactive hyperaemia (area under the LDF curve above baseline) was
      significantly less on the swollen side (P = 0.03), although peak flux was not
      significantly different. Inspiratory gasp, cool reflex, arm dependency and core
      heat load produced changes of similar magnitude in both arms. It appears that
      sympathetic neural control and local vasoconstrictor control in arm dependency
      are normal in arm lymphoedema but that locally mediated vasodilator control is
      impaired. In addition, baseline skin blood flow may be reduced in this condition.
      The results provide no support for impairment of vascular tone as a contributory
      factor to the oedematous state.

PMID- 8737079
TI  - The effect of exposure to increased hydrostatic pressure up to 46 ATA on
      respiratory sinus arrhythmia in humans.
AB  - Respiratory sinus arrhythmia (RSA) has been used as a non-invasive estimate of
      vagal tone to determine whether the reduction in resting heart rate commonly seen
      when humans are exposed to increases in the ambient pressure is associated with
      changes in vagal autonomic control. Two sets of divers (n = 4) were examined
      during two simulated saturation dives, one to 46 atmospheres absolute (ATA) and
      another to 37 ATA. A significant reduction in resting heart rate was seen in both
      dives upon exposure to high pressure compared with controls at 1 ATA. The
      reduction in heart rate seen at increased pressure was consistent regardless of
      respiratory rate, indicating that moderate changes in respiratory rate do not
      affect heart rate under these conditions. No changes in the overall magnitude of
      RSA were observed over a range of respiratory rates during either dive compared
      with control values at 1 ATA. During both dives, RSA was significantly larger (P
      < 0.05) at low respiratory rates compared with higher rates for both 1 ATA
      controls and at high pressure. The presence of a hyperbaric bradycardia strongly
      suggests that vagal tone is altered during hyperbaric exposure; however, the lack
      of change in the magnitude of RSA at high pressure brings into question the
      viability of using RSA as an accurate indicator of vagal tone and this lack of
      correspondence deserves further investigation.

PMID- 8737080
TI  - Accumulation of the endogenous L-arginine analogue NG-monomethyl-L-arginine in
      human end-stage renal failure patients on regular haemodialysis.
AB  - We measured plasma levels of L-arginine, its analogue NG-monomethyl-L-arginine (L
      NMMA), and related amino acids in normal subjects and uraemic patients (n = 31),
      before and after haemodialysis. Plasma levels of L-arginine were reduced to less
      than half of normal values in uraemic subjects compared with controls, and were
      not affected by haemodialysis. L-NMMA was not detectable in non-uraemic subjects,
      but markedly elevated in uraemic patients. In parallel, we used human red blood
      cells as a model to study the effect of L-NMMA upon the transport of L-arginine.
      L-NMMA trans-stimulated L-arginine transport significantly, confirming that L
      arginine and L-NMMA share common transport pathways. Our results suggest altered
      L-arginine metabolism and the presence of an increased concentration of a NO
      synthase inhibitor in uraemia. We propose that alterations in plasma L-arginine
      levels and increased production of L-arginine analogues will alter NO synthesis
      and may help to explain some pathological changes seen in uraemia.

PMID- 8737081
TI  - Molecular biology of the amiloride-sensitive epithelial Na+ channel.
AB  - The amiloride-sensitive epithelial Na+ channel is formed by the assembly of three
      homologous subunits, alpha, beta and gamma. The channel is characterized by its
      sensitivity to amiloride and to some amiloride derivatives, such as phenamil and
      benzamil, by its small unitary conductance (approximately 5 pS), by its high
      selectivity for lithium and sodium, and by its slow kinetics. The alpha-, beta-,
      and gamma-proteins share significant identity with degenerins, a family of
      proteins found in the mechanosensory neurons and interneurons of the nematode
      Caenorhabditis elegans. They are also homologous to FaNaCh, a protein from Helix
      aspersa nervous tissues, which corresponds to a neuronal ionotropic receptor for
      the Phe-Met-Arg-Phe-NH2 peptide. All these proteins contain a large extracellular
      loop, located between two transmembrane alpha-helices. The NH2 and COOH terminal
      segments are cytoplasmic and contain potential regulatory segments that are able
      to modulate the activity of the channel. Accordingly, in Liddle syndrome, in
      which patients develop a form of genetic hypertension, mutations within the
      cytoplasmic COOH terminal of the beta- and gamma-chains of the epithelial Na+
      channel lead to a hyperactivity of the channel. Epithelial Na+ channel activity
      is tightly controlled by several distinct hormonal systems, including
      corticosteroids and vasopressin. In kidney and colon, aldosterone is the major
      sodium-retaining hormone, acting by stimulation of Na+ reabsorption through the
      epithelium. In the distal colon from steroid-treated animals, a large increase in
      beta- and gamma-subunit transcription is observed, whereas the alpha-subunit
      remains constitutively transcribed. In kidney, RNA levels of the three subunits
      are not altered by aldosterone, suggesting that other mechanisms control Na+
      channel activity in that tissue. In lung, the glucocorticoids are positive
      regulators of the channel activity, especially around birth, and act via an
      increased transcription of the three subunits.

PMID- 8737082
TI  - G protein regulation of alveolar ion channels: implications for lung fluid
      transport.
AB  - Vectorial ion flow across the alveolar epithelium provides the driving force for
      lung fluid secretion in the prenatal lung and for fluid reabsorption at birth and
      thereafter into adult life. Fluid secretion is dependent upon 'active'
      accumulation of Cl- into the lumen of the developing lung and any factor which
      interupts the production of this liquid template results in life-threatening
      abnormalities in lung growth. The direction of fluid flow is reversed at birth to
      bring about the reabsorption of the lung fluid so that gaseous exchange can be
      initated successfully in the neonate. This functional switch at birth involves
      active Na+ reabsorption; failure of this mechanism to activate adequately
      contributes to respiratory distress in the newborn. Although beta 2-adrenoceptor
      cAMP-protein kinase activation provides a basic model for the switch, it is clear
      that local regulation of many of the components in the switching cascade are
      important to the overall efficiency with which it is achieved. Co-localized with
      apical Cl- and Na+ channels are pertussis toxin-sensitive G proteins, which exert
      their regulatory effects principally by direct protein-channel interactions. The
      modulation of channels by local G proteins is finely tuned by negative feedback
      mechanisms, which may include a novel double-bond specific fatty acid regulation
      of G protein turnover and the paracrine effects of locally produced eicosanoids.
      An understanding of how these overlapping pathways integrate to produce the
      smooth and ordered transition from Cl- secretion to Na+ absorption will allow the
      design of rational treatments for conditions that are characterized by
      disfunctional lung fluid homeostasis.

PMID- 8737083
TI  - Role of the actin cytoskeleton in the regulation of the cystic fibrosis
      transmembrane conductance regulator.
AB  - The anion-selective channel CFTR (cystic fibrosis transmembrane conductance
      regulator), whose dysfunction is responsible for the onset of cystic fibrosis, is
      regulated by cAMP through the activation of protein kinase A (PKA). The nature of
      this activation process is unknown. In the present study, patch-clamp techniques
      were applied to both mouse mammary adenocarcinoma cells expressing human
      epithelial CFTR (CFTR cells) and cultured neonatal rat ventricular myocytes
      (NRVM), to determine whether CFTR is modulated by the actin cytoskeleton, and
      whether the actin cytoskeleton may be implicated in the cAMP-stimulated
      activation of the channel protein. Acute changes in the actin cytoskeleton by
      addition of cytochalasin D (CD) activated whole-cell currents in CFTR cells and
      NRVM. Addition of actin to excised, inside-out patches also activated CFTR. A
      functional characterization of CFTR in either cell type included cAMP-induced,
      linear whole-cell and single-channel currents in symmetrical Cl-, permeability to
      ATP, and inhibition by either diphenylamine-carboxylate (DPC) or a monoclonal
      antibody raised against CFTR. Incubation of CFTR cells and NRVM with CD for over
      6 h prevented CFTR activation either by the cAMP pathway under whole-cell
      conditions or by PKA under excised inside-out conditions. Thus a complete
      derangement of the actin cytoskeleton prevents the cAMP-dependent activation of
      CFTR. CFTR activation, however, was restored by subsequent addition of actin. In
      summary, changes in actin filament organization modulate CFTR channel activity by
      a mechanism entailing a direct interaction between actin filaments and CFTR.

PMID- 8737084
TI  - Evidence for independent Cl- and HCO3- secretion and involvement of an apical
      Na(+)-HCO3- cotransporter in cultured rat epididymal epithelia.
AB  - Electrogenic chloride and bicarbonate secretion by cultured rat epididymal
      epithelia was studied using the short-circuit current (ISC) technique. When
      incubated in normal solution, 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic
      monophosphate (cpt-cAMP) caused a rise in the ISC, which was attributable to Cl-
      and HCO3- secretion. Cl- secretion was found to contribute to the initial
      transient phase, whereas HCO3- secretion contributed to the sustained phase of
      the response. HCO3- secretion involves a basolaterally placed Na(+)-H+ exchanger
      and apical anion channel, most probably the cystic fibrosis transmembrane
      conductance regulator (CFTR). There is also evidence that an apical electrogenic
      Na(+)-HCO3- cotransporter is involved in HCO3- exit. CFTR accounted for 70% of
      HCO3- secretion, while the Na(+)-HCO3- cotransporter accounted for 30%. The
      possibility that the cotransporter may serve as an alternative pathway for HCO3-
      secretion in cystic fibrosis is discussed.

PMID- 8737085
TI  - Role of mitochondria-rich cells in epithelial chloride uptake.
AB  - Uptake of NaCl by amphibian tight epithelia, such as skin, urinary bladder and
      collecting duct, requires considerable thermodynamic work. By calculation it is
      demonstrated that NaCl absorption from dilute external solutions ([NaCl]
      approximately 1 mM) demands more energy than can be provided by the Na(+)-K(+)
      ATPase alone. Thus, in addition to the Na+ pump, another transport ATPase must be
      involved. Previously, we have suggested that the other transport ATPase is an
      apical proton pump in mitochondria-rich (MR) cells. By driving an apical Cl(-)
      HCO3- exchange, a rheogenic H+ pump would energize entrance of Cl- across the
      apical membrane. Since Cl- channels are present in the basolateral membrane, the
      net result would be a transcellular active rheogenic uptake of Cl-, and secretion
      of H+ and HCO3-. At higher external concentrations, the Cl- uptake by MR cells is
      driven by the Na+ pump-generated transepithelial electrical potential difference,
      which also requires the presence of apical Cl- channels. Electrophysiological
      methods have been developed by which we have been able to study the polarity of
      single MR cells and identify apical and basolateral transport systems. We have
      verified the existence of rheogenic H+ pumps in the apical membrane and Cl-
      channels in both membranes.

PMID- 8737086
TI  - The cellular physiology of articular cartilage.
AB  - The cells of articular cartilage, or chondrocytes, live in an unusual and
      constantly changing physicochemical environment. They receive poorly understood
      signals during the loading of the tissue and produce, through a balance between
      macromolecular synthesis and degradation, a mechanically resilient extracellular
      matrix. Matrix turnover is influenced by changes to the intracellular composition
      (cell volume, pH and ionic content) of chondrocytes, and there are suggestions
      that this is altered in the disease process of osteoarthrosis. However, there is
      little information on the fundamental aspects of articular cartilage cellular
      physiology, which is essential if the factors controlling cartilage integrity in
      health and disease are to be understood. The present short review focuses on some
      of the membrane transporters of chondrocytes involved in volume regulation,
      electrophysiology and the regulation of intracellular pH.

PMID- 8737087
TI  - Modulation of vagal actions on heart rate produced by inhibition of nitric oxide
      synthase in the anaesthetized ferret.
AB  - We have examined a possible role for nitric oxide in the efferent vagal control
      of heart rate of the anaesthetized ferret, using stimulation of the motor fibres
      of the right vagus at supramaximal intensities and increasing frequencies.
      Propranolol was used to block beta-adrenergic actions on the heart. L-NAME (50
      100 mg i.v.) significantly reduced the bradycardia induced by vagal stimulation
      at all frequencies tested (1-15 Hz); subsequent infusion of L-arginine (100-200
      mg i.v.) restored the vagally induced heart rate responses to control levels.
      These results strongly suggest a role for nitric oxide in modulating the vagally
      mediated control of heart rate.

PMID- 8737088
TI  - Passive smoking and early arterial damage.

PMID- 8737089
TI  - Incessant ventricular tachycardia: a lost case or new hope?

PMID- 8737090
TI  - Economic aspects of treatment with captopril after MI.

PMID- 8737091
TI  - Chlamydia and coronary heart disease.

PMID- 8737092
TI  - Magnesium and acute myocardial infarction: misunderstood ion or irrelevant
      molecule?

PMID- 8737093
TI  - Unipolar cardioverter/defibrillator systems implanted under local anaesthesia--a
      further step to feasibility and safety.

PMID- 8737094
TI  - Progress in exercise electrocardiography.

PMID- 8737095
TI  - Hormone replacement therapy: a useful tool in the prevention of coronary artery
      disease in postmenopausal women? Working Group on Women and Cardiovascular
      Disease of The Netherlands Heart Foundation.

PMID- 8737096
TI  - Do magnetic resonance techniques contribute to the management of clinical
      problems?

PMID- 8737097
TI  - Should all patients with atrial fibrillation receive warfarin? Evidence from
      randomized clinical trials.
AB  - Anticoagulants should be used more widely in patients with atrial fibrillation.
      Legitimate concerns exist about the risk/benefit ratio in younger patients with
      no risk factors and in patients over the age of 75 years. Use of lower doses of
      anticoagulation (potential target range INR of 1.5-2.5) than used heretofore is
      probably the solution to most of the problems associated with anticoagulation,
      but conclusive proof of the efficacy of this strategy is needed. Although aspirin
      may reduce the risk of stroke the effect may be no more than among patients with
      a similar level of cardiovascular risk factors and in sinus rhythm. As such,
      aspirin is a valid alternative for patients with atrial fibrillation at a low
      risk of stroke but should not be used as an excuse to withhold anticoagulants in
      patients at greater risk. Several larger studies investigating the effects of
      different intensities of anticoagulation and the use of aspirin-warfarin
      combinations are underway. Indeed SPAF-III, comparing a combination of low dose
      warfarin and aspirin with formal anticoagulation has been stopped and reported in
      March 1996. A summary of the results will appear in the July issue.
      Identification of the minimum effective dose of warfarin and effective monitoring
      systems remain a priority.

PMID- 8737098
TI  - Association of Chlamydia pneumoniae and acute coronary heart disease events in
      non-insulin dependent diabetic and non-diabetic subjects in Finland.
AB  - OBJECTIVE: It has been suggested that Chlamydia pneumoniae, a Gram-negative
      intracellular bacterium, is a risk factor for both myocardial infarction and
      chronic coronary heart disease. Previous studies have been done predominantly in
      non-diabetic subjects and thus the effect of diabetes on the association between
      C. pneumoniae antibodies and coronary heart disease has not been analysed. The
      aim of our study was to investigate the association between prior chlamydial
      infection and the risk of serious coronary heart disease events (myocardial
      infarction or coronary death) in a 7-year prospective study of cohorts of
      diabetic and non-diabetic subjects in two areas of Finland. RESULTS: It was found
      that the prevalence of elevated chlamydial antibodies at baseline was higher in
      nondiabetic subjects who had serious coronary heart disease events during the
      follow-up than in subjects without coronary heart disease events (32 vs 15%,
      relative risk 2.56, P = 0.013) in East Finland. In non-diabetic subjects living
      in West Finland we did not find this association. The association between the C.
      pneumoniae antibodies and coronary heart disease events did not markedly change
      after controlling for other risk factors for coronary heart disease (OR 2.44, P =
      0.055) in non-diabetic subjects living in eastern Finland. In diabetic patients
      we did not find any association between chlamydial antibodies and coronary heart
      disease events. CONCLUSION: We found an association between C. pneumoniae
      antibodies and coronary heart disease events in non-diabetics living in eastern
      Finland. This association remained strong even after controlling for the other
      risk factors for coronary heart disease. In diabetic patients with high risk for
      coronary heart disease, C. pneumoniae was not a risk factor for coronary heart
      disease.

PMID- 8737099
TI  - Non-invasive prediction of reperfusion and coronary artery patency by continuous
      ST segment monitoring in the GUSTO-I trial.
AB  - In the GUSTO-I ECG ischaemia monitoring substudy, 1067 patients underwent
      continuous ST segment monitoring, using vector-derived 12-lead (406 patients), 12
      lead (373 patients) and 3-lead Holter (288 patients) ECG recording systems.
      Simultaneous angiograms at 90 or 180 min following thrombolytic therapy were
      performed as a part of the prospective study in 302 patients. Infarct vessel
      patency was established as TIMI perfusion grades 2 or 3 and occlusion as TIMI
      perfusion grades 0 or 1. Coronary artery patency was predicted from ST trends up
      to the time of angiography. Predictive values at 90 and 180 min after the start
      of thrombolysis were 70% and 82% for patency and 58% and 64% for occlusion,
      respectively. In retrospect, accuracy appeared greatest (79-100%) in patients
      with extensive ST segment elevation (> or = 400 microV), if both speed of ST
      recovery and extent of ST segment elevation were taken into account. Although the
      three recording systems differed considerably in signal processing, no
      significant difference in accuracy was demonstrated among these systems. We
      conclude that continuous ECG monitoring may help select high risk patients
      without apparent reperfusion who may benefit from additional reperfusion therapy.
      As ST recovery may occur early after the start of thrombolytics and accuracy of
      the test is related to peak ST levels, the use of on-line ECG monitoring devices
      on emergency wards and cardiac care units is recommended.

PMID- 8737100
TI  - The QRS score: a promising new exercise score for detecting coronary artery
      disease based on exercise-induced changes of Q-, R- and S-waves: a relationship
      with myocardial ischaemia.
AB  - BACKGROUND: Recently, a new exercise test criterion diagnosing coronary artery
      disease was proposed, based on a composite of changes in Q-, R- and S-waves: the
      QRS score. We compared this new criterion with conventional ST-segment depression
      and other compositions of Q-, R- and S-wave changes in patients and normals and
      related the QRS score to reversible thallium-201 scintigraphic defects and ST
      segment depression as markers for ischaemia. The influence of beta-blockade on
      the QRS score was also studied. METHODS: The study population consisted of 155
      persons with 53 normals (group I) and 102 patients with documented coronary
      artery disease (group II). Another 20 patients (group III) with proven coronary
      artery disease and a positive exercise test by ST-segment criteria were studied
      for the influence of beta-blockade on the QRS score. A symptom-limited exercise
      protocol according to the modified Bruce protocol was used. For the QRS score, Q
      , R- and S-wave amplitudes which could be recovered immediately were subtracted
      from pretest values: delta Q, delta R, delta S respectively. The score was
      calculated by the formula: (delta R - delta Q - delta S)AVF + (delta R - delta Q 
      delta S)V5. RESULTS: Using a cut-off point of > 5 as normal, the QRS score
      resulted in a sensitivity of 88.2%, a specificity of 84.8% and a predictive
      accuracy of 87.1%. For ST-segment depression these values were 54.9%, 83% and
      64.5% respectively (P < 0.001 compared to the QRS score). Predictive accuracies
      of changes in Q-, R- and S-waves in leads AVF and V5 separately, combinations of
      changes and combining the two leads, resulted-with the exception of solitary S
      wave changes-in predictive accuracies higher than those of ST-segment depression,
      but all were lower than the QRS score. We found a significant correlation between
      the QRS score, the summed ST-segment depression (P < 0.004) and the extent of
      reversible thallium-201 defects (P < 0.001). Applying Bayes' theorem, the
      combination of an abnormal QRS score and ST-segment depression resulted in the
      highest post-test risk for coronary artery disease and a normal QRS score without
      ST-segment depression in the lowest post-test risk. The QRS score and the maximal
      ST-segment depression changed significantly under the influence of beta-blockade
      (P < 0.02 and P < 0.001 respectively). CONCLUSION: Our data suggest that an
      abnormal QRS score reflects myocardial ischaemia. Furthermore, for the
      interpretation of the exercise test, the combined analysis of ST-segments and the
      QRS score is of value for the prediction of the presence or absence of coronary
      artery disease and its follow-up.

PMID- 8737101
TI  - High-dose intravenous magnesium attenuates complement consumption after acute
      myocardial infarction treated by streptokinase.
AB  - OBJECTIVE: This study was designed to detect changes in complement levels
      following acute myocardial infarction and to test whether magnesium sulphate
      (MgSO4) administration interferes with the complement response that follows acute
      myocardial infarction. DESIGN: Twenty-nine patients with acute myocardial
      infarction treated with streptokinase were included and randomly assigned to
      three treatment groups. In groups A and B, a bolus of 1 g MgSO4 was infused
      intravenously followed by 4 g (group A) and 14 g (group B) MgSO4 for 24 h while
      normal saline was administered in group C (control). Blood samples for C3, C4 and
      CH-100 were obtained at baseline and repeatedly during the 48 h following the
      initiation of magnesium infusion. RESULTS: In groups A and C, a remarkable
      decrease in the levels of C3, C4 and CH-100 was observed when measured 1 h after
      the end of streptokinase infusion and thereafter for the ensuing 48 h compared to
      baseline values (P < 0.05). In group B, the decrease in these complement elements
      was attenuated, and a significant (P < 0.05) delayed decrease of C3 and C4 was
      observed only at 24 h and later up to 48 h. The mean level of CH-100 in group B
      was significantly depressed compared to baseline from 3 h and thereafter up to 48
      h. Mean C3 values plotted against observation time differed between the three
      groups (P = 0.021). A similar trend was observed for C4 (P = 0.133) but not for
      CH-100 (P = 0.46). CONCLUSION: (1) Complement elements are being consumed
      following acute myocardial infarction treated by streptokinase. (2) High-dose
      intravenous magnesium attenuates the complement process following acute
      myocardial infarction. (3) These results might signify that magnesium modulates
      the inflammatory response that follows infarction.

PMID- 8737102
TI  - Endothelial dysfunction of the non-infarct related, angiographically normal,
      coronary artery in patients with an acute myocardial infarction.
AB  - BACKGROUND: Patients with acute myocardial infarction and single-vessel disease
      may have early atherosclerosis in other angiographically normal coronary
      arteries. METHODS: Coronary endothelial responses were analysed in 20 non
      diabetic patients with an acute myocardial infarction and one-vessel disease. In
      an angiographically normal, non-infarct related, coronary artery serial
      acetylcholine doses of 10(-7) M, 10(-6) M, 10(-5) M and 10(-4) M and
      nitroglycerin 40 micrograms were infused over 3 min. The responses of the
      coronary vessel were measured with quantitative angiography. Coronary blood flow
      was also measured with a Doppler catheter in 11 of the 20 patients. RESULTS: Four
      patients showed a trend towards vasodilation during acetylcholine infusion in the
      proximal and distal segments: from 2.49 +/- 0.23 mm to 2.95 +/- 0.42 mm and 2.43
      +/- 0.56 mm to 2.81 +/- 0.66 mm, respectively. Coronary vascular resistance
      decreased to 57 +/- 4% (P = 0.03). The other 16 patients presented
      vasoconstriction in the proximal and distal segments: 2.61 +/- 0.75 mm to 2.03 +/
      0.65 mm (P = 0.0001), and 2.40 +/- 0.58 to 1.81 +/- 0.56 mm (P = 0.0036),
      respectively. Nitroglycerin caused vasodilation in the proximal (2.69 +/- 0.61
      mm, P = 0.017, ANOVA) and distal segments (2.48 +/- 0.45 mm, P = 0.009, ANOVA).
      Coronary vascular resistance increased to 141 +/- 43% (P = 0.03) over the basal
      value in this group of patients. CONCLUSION: Endothelial dysfunction of the
      epicardial and resistance vessels was found in angiographically normal coronary
      arteries of patients with one-vessel disease in 75% of this population.

PMID- 8737103
TI  - Differences in the morphology of unstable and stable coronary lesions and their
      impact on the mechanisms of angioplasty. An in vivo study with intravascular
      ultrasound.
AB  - The aim of this study was to compare the morphology of stable and unstable
      coronary lesions using intravascular ultrasound in patients undergoing coronary
      balloon angioplasty and to determine whether lesion morphology had any influence
      on the mechanism of balloon angioplasty. Thirty three (15 stable and 18 unstable)
      patients undergoing single lesion percutaneous transluminal coronary angioplasty
      were studied with intravascular ultrasound before and after intervention. All
      examinations, recorded on S-VHS video tape, were studied off-line and matched
      sites from the point of minimum lumen area after the procedure and the
      corresponding site prior to intervention were compared. The morphology of lesions
      before intervention was noted and the mechanisms of angioplasty (vessel stretch,
      lesion remodelling and lesion tears) were determined by comparing pre- and post
      interventional morphology and dimensions. The only significant morphological
      difference between stable and unstable lesions was the presence of a demarcated
      inner layer in unstable lesions, delimited by a fine circumferential line. This
      pattern was noted in 77% (14/18) of unstable lesions and in 7% (1/15) of stable
      lesions (P < 0.01). Unstable lesions tended to have more echolucent zones than
      stable lesions (72% (13/18) vs 46% (7/15), P = 0.13). The mechanisms of
      angioplasty were also found to differ. Whereas lesion remodelling (or
      'compression') was seen in 77% (14/18) of unstable lesions, it occurred in only
      13% (2/15) of stable lesions and mean lesion cross-sectional area reduction was
      greater in unstable lesions, - 14.8 +/- 8.3% (2.1 +/- 1.3 mm2) compared to stable
      lesions, - 4.1 +/- 8.4% (0.42 +/- 0.9 mm2), P < 0.01. In contrast, vessel stretch
      was seen more frequently in stable lesions (73%, 11/15) compared to unstable
      lesions (22%, 4/18) P < 0.01 and the mean increase in vessel cross-sectional area
      was + 13.5 +/- 6.8 (1.6 +/- 0.9 mm2) in stable lesions compared to + 5.5 +/- 5.6%
      (0.8 +/- 0.9 mm2) in unstable lesions, P < 0.01. Lesion tear was present to a
      similar degree in both groups of patients. In this observational study we found a
      set of echographic markers that distinguished unstable lesions. The mechanisms of
      angioplasty differed between stable and unstable angina, with greater lesion
      remodelling seen in unstable lesions and vessel stretch in stable lesions. Taken
      together, these findings suggest that the markers we describe may be echographic
      indicators of mural thrombus.

PMID- 8737104
TI  - Economic aspects of treatment with captopril for patients with asymptomatic left
      ventricular dysfunction in The Netherlands.
AB  - OBJECTIVE: To estimate the costs and effects of preventive treatment with
      captopril compared with the current treatment policy in patients with
      asymptomatic left ventricular dysfunction after a myocardial infarction. METHODS:
      Estimates of effects are based on the results of the SAVE trial. Costs are
      estimated on the basis of current treatment patterns in four Dutch hospitals. All
      knowledge is incorporated in a mathematical model extrapolating the SAVE results
      to 20 years. RESULTS AND CONCLUSIONS: Captopril treatment is expected to increase
      survival at certain costs. The average additional costs per patient are estimated
      at DF1 2,491 in 4 years and at DF1 8,723 in 20 years of treatment. Costs per
      additional survivor after 4 years are estimated at DF1 69,126. After
      extrapolation of the results of the SAVE trial to 20 years, costs per life-year
      gained can be estimated at DF1 15,799. From univariate sensitivity analysis it
      appears that the results are highly sensitive for the costs of treatment with
      captopril and the occurrence and prevention of clinical heart failure. Varying
      all estimates randomly between upper and lower limits-in 5,000 simulations-an
      estimate of costs per life-year gained of DF1 15,729 is made for 20 years of
      treatment, with 95% of all estimates between DF10 and DF1 50, 000. On a national
      level, undiscounted costs are expected to increase up to approximately DF1 42
      million annually during the first 40 years after introduction of the preventative
      strategy.

PMID- 8737105
TI  - Effects of beta receptor antagonists on left ventricular function in patients
      with clinical evidence of heart failure after myocardial infarction. A double
      blind comparison of metoprolol and xamoterol. Echocardiographic results from the
      Metoprolol and Xamoterol Infarction Study (MEXIS).
AB  - Two hundred and ten patients with clinical evidence of heart failure, developing
      after an acute myocardial infarction, were randomized to treatment with the beta
      1-receptor antagonist metoprolol 50-100 mg b.i.d. (n = 106) or the beta 1
      receptor partial agonist xamoterol 100-200 mg b.i.d. (n = 104). Left ventricular
      systolic and diastolic function were assessed with echocardiography and
      transmitral Doppler cardiography before and after 3 and 12 months of double-blind
      treatment. E-point septal separation and percent left ventricular fractional
      shortening were used as indices of systolic function. The ratio between peak
      early and late mitral diastolic flow (E/A ratio) and isovolumic relaxation time
      were used as indices of diastolic function. In the xamoterol group, there was a
      deterioration in E-point septal separation (P < 0.05). A difference between the
      treatment groups was present both at 3 months (E-point septal separation 11.4 vs
      13.0 mm, P < 0.01, fractional shortening 27.1 vs 25.2%, P < 0.05) and 12 months
      (E-point septal separation 11.1 vs 13.2 mm. P < 0.005, fractional shortening 26.9
      vs 25.0%, P < 0.05). E/A ratio increased in the metoprolol group (P < 0.05) but
      not in the xamoterol group. At 3 months there was a significant difference (0.85
      vs 0.67, P < 0.005) between the groups but not at 12 months. In comparison with
      the beta 1-receptor antagonist metoprolol, the beta 1-receptor partial agonist
      xamoterol impaired left ventricular systolic function in patients with clinical
      evidence of heart failure after an acute myocardial infarction.

PMID- 8737106
TI  - Ventilatory response to exercise and to carbon dioxide in patients with heart
      failure.
AB  - Patients with heart failure exhibit an increased ventilatory response to
      exercise; their slope of the overall ventilation/carbon dioxide production ratio
      (VE/VCO2) is elevated. This elevation is related to impaired exercise performance
      and is commonly explained by an increased ventilation-perfusion mismatch.
      However, the concept of afferents to the respiratory centre modulating
      ventilation during exercise has been raised. In healthy subjects, ventilation
      during exercise is related to the hypercapnic ventilatory response during
      rebreathing. This is explained by a similar response of the respiratory centre to
      different stimuli. The aim of this study was to analyse the relationship between
      the ventilatory response to exercise and to carbon dioxide in patients with
      chronic heart failure. The hypercapnic ventilatory response was measured at rest
      using the rebreathing method in 31 patients with chronic heart failure and a left
      ventricular ejection fraction < 40% and 25 controls. Thereafter a maximal bicycle
      exercise test with evaluation of VE/VCO2 was performed. The maximal oxygen uptake
      during exercise was 13.1 +/- 5.2 ml. min-1.kg-1. The slope of the hypercapnic
      ventilatory response was normal (1.1 +/- 0.81. min-1. mmHg-1) but minute
      ventilation breathing room air was increased in the patients as compared to the
      controls. VE/VCO2 during exercise was positively correlated to the hypercapnic
      ventilatory response (r = 0.70; P < 0.00001). This relationship supports the
      concept that in patients with heart failure, ventilation during exercise is not
      only influenced by an increased ventilation-perfusion mismatch but is in part
      mediated by the responsiveness of the respiratory centre. Different afferents to
      the respiratory centre, such as central command or muscle ergoreflex may play a
      role in modulating ventilation during exercise.

PMID- 8737107
TI  - Catheter ablation of incessant ventricular tachycardia: acute and long-term
      results.
AB  - SUBJECTS: Seventeen patients with incessant ventricular tachycardia refractory to
      anti-arrhythmic therapy underwent catheter ablation between 1987 and 1993.
      Fifteen patients had coronary heart disease and two had dilated cardiomyopathy.
      The mean age of the patients was 65 +/- 8 and the mean left ventricular ejection
      fraction was 31 +/- 9%. METHODS: Ablation sites were selected on the basis of
      endocardial activation mapping, concealed entrainment or bundle branch mapping.
      Catheter ablation was performed with direct current in nine patients and with
      radiofrequency energy in eight patients. Incessant ventricular tachycardia was
      terminated by catheter ablation in all 17 patients. RESULTS: One patient died
      after the ablation procedure due to pericardial tamponade. During
      electrophysiological testing 5-14 days later, 7 of 16 patients (44%) had
      inducible sustained or non-sustained ventricular tachycardia. Five of them
      underwent implantation of an automatic cardioverter/defibrillator, and three of
      these experienced discharges of the device during a mean follow-up of 30 +/- 12
      months. another patient underwent implantation of a cardioverter/defibrillator
      after spontaneous recurrence of ventricular tachycardia. Out of the nine patients
      without inducible ventricular tachycardia, one died as a result of sudden cardiac
      death, and another had spontaneous ventricular tachycardia. Thus, ventricular
      tachycardia recurred clinically in 6 of 16 patients (38%), in whom ventricular
      tachycardia with the same morphology as that of the ablated ventricular
      tachycardia could be determined only in one patient. CONCLUSION: Catheter
      ablation is the method of choice for the emergency treatment of patients with
      incessant ventricular tachycardia. Due to the high risk of recurrence, additional
      anti-arrhythmic management, such as the implantation of a
      cardioverter/defibrillator, has to be considered.

PMID- 8737108
TI  - Implantation of a unipolar cardioverter/defibrillator system under local
      anaesthesia.
AB  - OBJECTIVE: To evaluate prospectively the safety and feasibility of the
      implantation of cardioverter/defibrillator systems under local anaesthesia.
      Conventionally, cardioverter/defibrillator systems are implanted under general
      anaesthesia. With the development of single-lead transvenous unipolar
      cardioverter/defibrillator systems for subpectoral implantation a pacemaker-like
      approach for device implantation appears applicable. METHODS: Implantation of a
      single-lead transvenous unipolar cardioverter/defibrillator under local
      anaesthesia with sedation for defibrillation threshold testing was performed in
      37 consecutive patients. The presenting arrhythmia was ventricular fibrillation
      in 13 patients, and monomorphic ventricular tachycardia in 24 patients. A 1%
      lidocaine solution was used for local anaesthesia, and midazolam was applied for
      sedation to perform defibrillation threshold testing. Arterial blood pressure,
      arterial oxygen saturation and heart rate were monitored throughout the
      procedure. The patient's tolerance of the implantation procedure was evaluated
      with a standardized questionnaire. RESULTS: The unipolar transvenous
      cardioverter/defibrillator system was implanted successfully in all patients
      under local anaesthesia. During defibrillation threshold testing, sufficient
      sedation was achieved with 12.5 +/- 3.7 mg midazolam. For determination of the
      defibrillation threshold 5.9 +/- 1.4 episodes of ventricular fibrillation were
      induced. The mean defibrillation threshold was 13.1 +/- 5.5 J, and the mean
      duration of the implantation procedure was 68 +/- 30 min. Mean heart rate, mean
      arterial blood pressure and arterial oxygen saturation were not significantly
      different before and after defibrillation threshold testing. Twenty-six patients
      (70%) were symptom-free throughout the implantation procedure; most of the
      remaining patients reported minor symptoms. There were no complications, and
      patients were discharged 2.2 +/- 0.7 days after implantation. In 12 patients,
      post-implant testing of the implantable cardioverter/defibrillators was performed
      successfully, without sedation, 2.8 +/- 1.4 days after as an outpatient
      procedure. CONCLUSION: Single-lead unipolar transvenous implantable
      cardioverter/defibrillator systems can be safely implanted under local
      anaesthesia with mild sedation for defibrillation threshold testing. The
      procedure is well tolerated.

PMID- 8737109
TI  - Spectral analysis of short term R-Tapex interval variability during sinus rhythm
      and fixed atrial rate.
AB  - Analysis of heart rate variability has been proven useful in stratifying post
      myocardial patients at risk and in evaluating autonomic dysfunction. Recently
      augmented inter-lead variability of the QT interval has been associated with
      increased mortality as a result of arrhythmia and proposed as a marker of
      dispersion of ventricular repolarization. As the duration of the QT interval is
      largely dependent upon the length of the preceding cardiac cycle it is tempting
      to analyse whether neural mechanisms might also directly exert additional
      modulation. Using autoregressive algorithms we therefore analysed RR and R-Tapex
      interval variabilities in 15 normal subjects during sinus rhythm and in six
      patients with a fixed atrial rate. In controls mean R-Tapex interval and variance
      measured on the vector magnitude were, respectively, 245 +/- 6 ms and 5.1 +/- 0.7
      ms2. Spectral analysis of R-Tapex indicated the presence of two spectral
      components which corresponded to the low and high frequency components of heart
      rate variability. In R-Tapex variability, high frequency (44 +/- 4 nu) was
      predominant over low frequency (29 +/- 4 nu). During controlled respiration, a
      manoeuvre associated with enhanced vagal modulation of sinus node, there was a
      further increase in high frequency (58 +/- 4 nu) whereas during tilt the low
      frequency component of R-Tapex variability became predominant (57 +/- 6 nu). In
      patients with a fixed atrial rate, variance was extremely low (3 +/- 0.9 ms2) and
      only a respiration-related high frequency component was recognizable in spectral
      analysis of RR and R-Tapex variabilities. This component was likely to depend
      upon mechanically induced changes in cardiac vector orientation. These data
      indicate that during sinus rhythm short-term R-Tapex interval variability is
      characterized by the same rhythmical components present in RR variability.
      However, the presence of a very low variance and of only a high frequency
      component in patients in whom the physiological variability of sinus node is
      abolished by atrial pacing. suggests that neural modulatory mechanisms do not
      exert a direct effect on the length of the R-Tapex interval.

PMID- 8737110
TI  - Use of transthoracic Doppler echocardiography combined with clinical and
      electrocardiographic data to predict acute pulmonary embolism.
AB  - Transthoracic echocardiography and continuous wave Doppler were prospectively
      performed in 132 out-patients with suspicion of pulmonary embolism, and who had
      no previous history of severe cardiac or pulmonary disease. Bedside
      echocardiography determined diagnosis other than pulmonary embolism in 55
      patients. Further study was completed in 70 patients; pulmonary embolism was
      found in 31 and excluded in 39. Significant differences were found as regards
      right ventricular diameter (27 +/- 8 vs 22 +/- 5 mm, P < 0.001), left ventricular
      diameter (41 +/- 9 vs 49 +/- 7 mm, P < 0.001), right over left ventricular
      diameter ratio (0.67 +/- 0.23 vs 0.43 +/- 0.15, P < 0.0001), tricuspid
      regurgitant flow peak velocity (2.9 +/- 0.4 vs 2.4 +/- 0.7 m.s-1, P < 0.0001),
      and abnormal septum motion (12 vs 4, P < 0.01). Multivariate analysis of
      echocardiographic data included a tricuspid regurgitant flow peak velocity
      greater than 2.5 m.s-1 and a right over left ventricular diameter ratio greater
      than 0.5 in a logistic model (sensitivity 93%, specificity 81%). The combination
      of echocardiographic and non-echocardiographic data included the two previous
      echocardiographic variables, together with signs of deep vein thrombosis, a deep
      S wave in lead D1, and a Q wave in lead D3 on the electrocardiogram in a logistic
      model (sensitivity 96%, specificity 83%). It can be concluded that emergency
      echocardiography, alone or combined with clinical examination and
      electrocardiogram, satisfactorily predicts acute pulmonary embolism.

PMID- 8737111
TI  - The deletion polymorphism of the angiotensin-converting enzyme gene is related to
      phenotypic differences in human arteries.
AB  - We hypothesized that angiotensin-converting enzyme (ACE) insertion/deletion
      polymorphism may be related to arterial phenotypic differences that could explain
      the adverse effects of deletion polymorphism. Accordingly, contractile responses
      to angiotensin I and II (0.1 nmol.1(-1)-1 micromol.1(-1), endothelium-dependent
      relaxation to methacholine (0.01-100 micromol.1(-1), and the effect of NG
      monomethyl-L-arginine (L-NMMA; 100 micromol.1(-1) on phenylephrine (10
      micromol.1(-1) induced contraction, were studied in isolated rings of internal
      mammary arteries obtained from patients undergoing coronary bypass surgery. The
      results were analysed according to the ACE genotype of the patient (II, n = 8;
      ID, n = 11; DD, n = 9) as well as the presence/absence of either allele. The
      arteries from patients with the D allele (ID/DD) displayed a lower sensitivity to
      methacholine (P < 0.05 vs II), which suggested that the capacity of the
      endothelium for nitric oxide release in response to stimulation was also lower.
      By contrast, the increase in phenylephrine-induced contraction, by pre-incubation
      with L-NMMA, was more pronounced in the group with the DD allele (31 +/- 5%) than
      with the ID (11 +/- 11%) and II alleles (1 +/- 11%, P < 0.05 vs DD), which
      suggested a higher level of basal nitric oxide release. Finally, the differences
      in the responses to angiotensin I and II, which were used to evaluate the
      vascular conversion of angiotensin I, indicated that the level of angiotensin I
      conversion was higher in patients with the D allele (ID/DD, P < 0.05 vs II). The
      findings of this study indicate that ACE insertion/deletion polymorphism is
      related to arterial phenotypic differences in endothelial function and
      angiotensin I conversion.

PMID- 8737112
TI  - A comparison of left ventricular myocardial velocity in diastole measured by
      magnetic resonance and left ventricular filling measured by Doppler
      echocardiography.
AB  - Abnormal diastolic left ventricular function is an early marker for myocardial
      disease and may be impaired even when global systolic function is normal.
      Subendocardial function is affected early in ischaemic heart disease and by
      altering left ventricular long axis motion, may contribute to abnormal
      transmitral pressure gradients. Regional myocardial long axis velocity in
      diastole measured by magnetic resonance was compared with left ventricular
      filling measured by Doppler echocardiography in 25 patients with coronary artery
      disease. Fifteen patients also underwent magnetic resonance assessment at the
      time of onset of early diastolic blood flow. The onset of diastolic long axis
      velocity preceded flow across the mitral valve by a mean of 46 ms. Mean long axis
      myocardial velocity correlated with peak early filling velocity (E) (r = 0.73, P
      < 0.001), early deceleration (r = -0.73, P < 0.001), and the early to late
      filling ratio (E/A) ratio (r = 0.6, P < 0.01). Maximum myocardial long axis
      velocity also correlated with peak early filling velocity (r = 0.56, P < 0.01),
      early deceleration rate (r = 0.63, P < 0.001), and the E/A ratio (r = 0.53, P <
      0.01). The variability of long axis velocity around the ventricle correlated
      inversely with peak early filling, (r = -0.7, P < 0.001), early deceleration (r =
      -0.56, P < 0.01), and the E/A ratio (r = -0.48, P < 0.02). Peak atrial filling
      velocity did not correlate with any measure of long axis myocardial velocity. We
      conclude that early diastolic long axis myocardial velocity has a significant
      effect on left ventricular filling.

PMID- 8737113
TI  - Dobutamine-induced and spontaneous sustained ventricular tachycardia in recent
      myocardial infarction.

PMID- 8737114
TI  - Internal mammary artery spasm immediately after grafting to the left anterior
      descending artery: diagnosis and treatment.

PMID- 8737115
TI  - Oxidative stress in clinical situations--fact or fiction?

PMID- 8737116
TI  - The role of leukocytes in tissue injury.
AB  - The recruitment of leukocytes to the sites of inflammation and leukocyte-derived
      inflammatory mediators contributes to the development of tissue injury associated
      with inflammatory diseases. The first step in the pathogenesis of inflammatory
      conditions is adhesion of circulating leukocytes to activated vascular
      endothelial cell in the inflamed tissues and subsequent transmigration through
      the endothelial cells. During these processes, leukocytes are activated to
      secrete a variety of substances such as growth factors, chemokines and cytokines,
      complement components, proteases, nitric oxide, and reactive oxygen metabolites,
      which are considered to be one of the primary sources of the tissue injury.
      Prevention or reduction of leukocyte-endothelial cell adhesion often results in a
      profound attenuation of the microvasculature and parenchymal cell dysfunction in
      various animal models of human inflammatory diseases. It has been shown that all
      aspirin-like non-steroidal anti-inflammatory agents share at least one
      characteristic in that all of these agents diminish the adhesive interactions
      required for the accumulation of leukocytes at the site of inflamed tissue. The
      challenge for future investigations will need to be carefully examined: the
      relations between leukocyte and endothelial cell interactions, the mechanisms of
      activation of leukocytes and endothelial cells, and the components of the
      signaling pathways. Information related to these topics will allow a better
      understanding of the role of leukocytes in inflammatory tissue injury and the
      development of novel therapeutic strategies.

PMID- 8737117
TI  - Mechanisms of secondary brain injury.
AB  - The mechanisms which lead to secondary brain damage following transient ischaemia
      are incompletely defined. As discussed in this hypothesis article, the events
      which lead to such damage could encompass (a) a perturbed membrane handling of
      calcium, leading to a slow, gradual increase in the free cytosolic calcium
      concentration (Ca2(i)), with subsequent calcium overload of mitochondria, (b) a
      sustained reduction of protein synthesis which, in the long run, deprives cells
      of enzymes or trophic factors essential to their survival, or (c) the initiation
      of an inherent program for cell death. Results obtained in ischaemia of brief to
      intermediate duration demonstrate that the ultimate cell death is heralded by a
      reduction in the respiratory capacity of isolated mitochondria. However, the
      results fail to demonstrate whether or not such a reduction precedes
      deterioration of the bioenergetic state which then precipitates cell death.
      Cyclosporin A (CsA) has recently been shown to dramatically improve the delayed
      CA1 damage following transient forebrain ischaemia. Since CsA is known to block a
      deleterious permeability transition (PT) in mitochondria from several tissues in
      response to calcium accumulation and oxidative stress, the results on CsA effects
      in forebrain ischaemia support a mitochondrial origin for the delayed cell death.
      Furthermore, comparisons with the effects of CsA and alpha-phenyl-N-tert-butyl
      nitrone (PBN) in thymocytes and other cells undergoing programmed cell death
      suggest that delayed neuronal damage occurs by a sequence of events akin to those
      leading to apoptotic cell death. However, whether cell death is apoptotic or
      necrotic may depend on the severity of the insult (and its duration). We
      speculate that the initial ischaemic transient leads to gradual mitochondrial
      calcium overload, the latter triggering a PT, and apoptotic or necrotic cell
      death. Since similar results have been obtained in normoglycaemic animals
      subjected to ischaemia of intermediate duration, and in animals with preischaemic
      hyperglycaemia, it seems likely that both increased ischaemia duration and
      hyperglycaemia accelerate damage to mitochondria in the reperfusion period.
      Recent results obtained in transient focal ischaemia of 2 h duration demonstrate
      that the free radical spin trap PBN reduces infarct size, even when given 1 or 3
      h after the start of reperfusion, thus providing a second window of therapeutic
      possibility. A major effect of the drug is exerted on the recovery of energy
      metabolism of the tissue since it reduces a secondary deterioration in the
      bioenergetic state, occurring after 2-4 h of reperfusion. At least in part, the
      spin trap may exert its effect by reducing microvascular dysfunction caused by
      oedema and to adhesion of polymorphonuclear (PMN) leucocytes, which give rise to
      an inflammatory response mediated by cytokines, lipid mediators, or free
      radicals. This contention is supported by the reduction in focal ischaemic damage
      by antibodies to adhesion molecules for PMNs. However, it has now been found that
      the secondary deterioration of the bioenergetic state of core and penumbral
      tissues are mirrored by corresponding changes in the respiratory functions of
      isolated mitochondria, suggesting that, also in this type of ischaemia, the
      mitochondria suffer secondary damage. It is conceivable that a significant
      fraction of malfunctioning mitochondria emanate from microvascular tissue,
      explaining why antibodies to adhesion molecules mitigate the ischaemic lesions.

PMID- 8737118
TI  - Cerebral microdialysis as a diagnostic tool in acute brain injury.
AB  - In the past 10 years, the management of brain injury has shown several advances.
      Besides new diagnostic tools many new tentative approaches have been
      investigated, such as jugular bulb measurement of oxygen and lactate differences
      and near-infrared spectroscopy. The latest tool is microdialysis, which uses a
      probe as an interface to the brain. This method uses internally perfused semi
      permeable membrane probes, which allow neurochemical water-soluble substances to
      be collected outside the brain for further analysis. Since the late 1980s the
      first results of microdialysis in neurointensive care show that chemical
      substances such as lactate, glucose, amino acids, metabolites of several
      biochemical mechanisms and electrolytes are measurable. This heterogeneous
      approach now waits for validation for clinical use and for the most challenging
      aspect, the clinical interpretation and use to improve therapy. The aim of this
      review is to describe the state of the art of this new technique, including our
      own experiences and concepts.

PMID- 8737119
TI  - Efficacy and mechanisms of action of the cytoprotective lipid peroxidation
      inhibitor tirilazad mesylate in subarachnoid haemorrhage.
AB  - Subarachnoid haemorrhage (SAH) following cerebral aneurysm rupture or trauma can
      result in the induction of secondary ischaemic brain damage via a decrease in
      microvascular perfusion, a disruption of the blood-brain barrier and consequent
      vasogenic oedema, and the delayed spasm of the major cerebral arteries (i.e.
      vasospasm). It is increasingly apparent that oxygen radical-induced, iron
      catalyzed lipid peroxidation (LP) within the subarachnoid blood and vascular wall
      plays a key role in the occurrence of these secondary events. Tirilazad mesylate
      is a potent cytoprotective inhibitor of LP that works by a combination of radical
      scavenging and membrane stabilizing properties. It has been demonstrated to
      attenuate the acute and delayed vascular consequences of SAH and to protect the
      brain against ischaemic insults. Much of its action is mediated by an effect on
      the vascular endothelium, although it also appears to exert some direct
      neuroprotection and to inhibit LP in the subarachnoid blood. These actions of
      tirilazad in experimental SAH are reviewed.

PMID- 8737120
TI  - Therapeutic approaches for the prevention of secondary brain injury.
AB  - The precise mechanisms underlying secondary brain damage after traumatic injury
      to the central nervous system (CNS) are not well understood, and delayed neuronal
      injury may result from pathological changes in neurotransmitter release,
      synthesis or generation of endogenous autodestructive neurochemicals and/ or
      inflammatory mediators, or alterations in endogenous protective or trophic
      factors. Recent identification of such factors and the elucidation of the timing
      of the neurochemical cascade following CNS injury provides a window of
      opportunity for therapeutic intervention with pharmacological compounds which
      modify synthesis, release, receptor binding or physiological activity of
      neurotoxic factors. A number of recent experimental studies have reported that
      pharmacological modification of the post-traumatic neurochemical milieu can
      promote functional recovery in a variety of animal models of CNS trauma. This
      paper summarizes recent work suggesting that pharmacological manipulation of
      several key neurotransmitter and neurochemical systems can attenuate neuronal
      damage and improve functional outcome associated with traumatic brain injury.

PMID- 8737121
TI  - In-vitro activity of sparfloxacin in comparison with currently available
      antimicrobials against respiratory tract pathogens.
AB  - Bacterial resistance to antimicrobial agents is an ever-increasing problem. The
      in-vitro activity of sparfloxacin compared with that of currently available
      antimicrobial agents against pathogens implicated in respiratory tract infections
      is reviewed. Sparfloxacin is a fluoroquinolone active against both penicillin
      susceptible and -resistant strains of Streptococcus pneumoniae. It is also active
      against many other respiratory tract pathogens and may be a suitable alternative
      for empirical therapy of community-acquired respiratory tract infections.

PMID- 8737122
TI  - Comparative in-vitro activity of sparfloxacin against genital pathogens.
AB  - The in-vitro activity of sparfloxacin against four pathogens commonly implicated
      in genital infections was compared with that of a number of other commonly
      administered antimicrobials. Sparfloxacin demonstrated excellent activity against
      Neisseria gonorrhoeae (MIC range of < or = 0.0002-5 mg/L for beta-lactamase
      producing strains, and < or = 0.0002-0.03 mg/L for non-beta-lactamase producing
      strains). This activity was similar to that of lomefloxacin and ciprofloxacin and
      was greater than that of ofloxacin. Sparfloxacin was more active against
      Ureaplasma urealyticum (MIC90 1 mg/L) than the other three quinolones (MIC90 4
      mg/L). Sparfloxacin was much more active against Mycoplasma hominis (MIC90 0.06
      mg/L) than the other quinolones (MIC90 1 mg/L). Sparfloxacin showed the most
      potent inhibitory and bactericidal activity of the quinolones against Chlamydia
      trachomatis with MIC and MBC of 0.06 mg/L (ofloxacin MIC and MBC 1 mg/L;
      ciprofloxacin and lomefloxacin MIC and MBC 2 mg/L). The results of this study and
      others performed by workers using different methods are consistently similar.
      Since sparfloxacin has broad activity against pathogens implicated in genital
      infections it may be a good therapeutic alternative for these syndromes.

PMID- 8737123
TI  - Pharmacokinetics of sparfloxacin in healthy volunteers and patients: a review.
AB  - In Caucasian volunteers and patients plasma sparfloxacin concentrations reached a
      peak of 1.2-1.5 mg/L between 3 and 6 h after a single 400 mg dose; T1/2 ranged
      from 16 to 22 h. The peak plasma concentration and the area under the plasma
      concentration-time curve exhibited dose-related increases but a slight decrease
      in the extent of absorption was observed following administration of doses above
      those recommended for clinical use. Renal clearance did not exceed 10% of the
      apparent plasma clearance. The urinary excretion of unchanged drug accounted for
      9-10% of the dose administered and that of its glucuronide for 27-38% of the
      dose. The biliary excretion of the drug and its glucuronide accounted for about
      1.5 and 11% of the dose administered, respectively. Following multiple-dose
      administration (200 mg daily after a loading dose of 400 mg on day 1), steady
      state concentrations were achieved following the second dose. The peak plasma
      concentration was 1.4 mg/L and the through concentration was 0.5 mg/L. The T1/2
      was approximately 20 h. Studies in patients show that the pharmacokinetics of
      sparfloxacin were not influenced by age but severe renal failure markedly
      impaired elimination of the parent drug (the T1/2 was approximately doubled in
      patients with renal failure), and glucuronide, requiring adjustment of the dosage
      regimen. In patients with liver cirrhosis but no cholestasis, the
      pharmacokinetics of sparfloxacin were not markedly altered, although the urinary
      excretion of the glucuronide was about twice that observed in healthy volunteers.
      No modification of the usual dosage is recommended for these patients.

PMID- 8737124
TI  - Pharmacokinetic interactions related to the chemical structures of
      fluoroquinolones.
AB  - Fluoroquinolone derivatives interact with methylxanthines (theophylline,
      caffeine) and metallic ion-containing drugs to different degrees. The rat appears
      to be a suitable model for predicting such interactions in man. It has been
      possible to determine the relationship between the chemical structure of the
      fluoroquinolone and the magnitude of the interaction. Fluoroquinolones with a
      bulky substituent at the position 8, such as sparfloxacin, lomefloxacin and
      fieroxacin, are less prone to interact with theophylline than those without an 8
      substituent, such as enoxacin. This substituent determines the planarity of the
      whole fluoroquinolone molecule and the interaction tends to be more significant
      for planar fluoroquinolones. Furthermore, a 4'-nitrogen atom in the 7-piperazinyl
      group is essential for the interaction to occur. The nitrogen atom is possibly
      the site that binds cytochrome P-450, which catalyses theophylline metabolism.
      The reduction in bioavailability of fluoroquinolones by concurrent administration
      of aluminium hydroxide is more striking for derivatives with fewer substituents
      on the essential structure and on the piperazinyl group, such as norfloxacin,
      ciprofloxacin and enoxacin. Substitution at the 5-position diminishes the
      interaction, which suggests that the 5-substituent may affect the formation
      and/or stability of unabsorbable chelate complex which is the probable cause of
      the interaction. These findings are potentially useful in designing
      fluoroquinolones less prone to drug interactions.

PMID- 8737125
TI  - A review of the penetration of sparfloxacin into the lower respiratory tract and
      sinuses.
AB  - There are a number of potential sites of infection in the lower respiratory
      tract. This review summaries the nature of these sites and the ways in which
      antibiotic penetration can be studied. The results of a single-dose and a
      multiple-dose study of the penetration of sparfloxacin into the respiratory tract
      are also provided. After a single oral dose of sparfloxacin 400 mg or a 400 mg
      loading dose on day 1 followed by 200 mg daily for 2 days, sparfloxacin
      concentrations in the bronchial mucosa, epithelial lining fluid and alveolar
      macrophages were higher than the corresponding concentrations in serum. Compared
      with other fluoroquinolones, sparfloxacin achieves higher concentrations at these
      sites. Sparfloxacin diffusion into maxillary sinus mucosa has been studied in
      patients with chronic maxillary sinusitis undergoing surgery. High concentrations
      of sparfloxacin were detected in sinus mucosa 2 to 5 h after administration of a
      single dose of sparfloxacin 200 or 400 mg.

PMID- 8737126
TI  - Study design, methodology and statistical analyses in the clinical development of
      sparfloxacin.
AB  - Many publications in the past 10 years have emphasised the difficulties of
      evaluating anti-infective drugs and the need for well-designed clinical trials in
      this therapeutic field. The clinical development of sparfloxacin in Europe,
      involving more than 4000 patients in ten countries, provided the opportunity to
      implement a methodology for evaluation and statistical analyses which would take
      into account actual requirements and past insufficiencies. This methodology
      focused on a rigorous and accurate patient classification for evaluability,
      subgroups of particular interest, efficacy assessment based on automation
      (algorithm) and individual case review by expert panel committees. In addition,
      the statistical analyses did not use significance testing but rather confidence
      intervals to determine whether sparfloxacin was therapeutically equivalent to the
      reference comparator antibacterial agents.

PMID- 8737127
TI  - Sparfloxacin for the treatment of community-acquired pneumonia: a pooled data
      analysis of two studies.
AB  - A pooled data analysis of two double-blind studies encompassing 1137 episodes of
      community-acquired pneumonia in hospitalised adults, of which 560 were treated
      with sparfloxacin and 577 were randomised to comparator antibacterial agents
      (amoxycillin/clavulanic acid, erythromycin or amoxycillin administered at
      reference dosages), was performed. The global efficacy rate at the end of
      treatment in evaluable patients treated with sparfloxacin was 88.3% compared with
      84.1% in those who received comparator antibacterial agents. This analysis
      verified the efficacy of this new aminofluoroquinolone, given orally once daily,
      in the treatment of community acquired pneumonia. The overall outcome favoured
      sparfloxacin for use in the empirical treatment of community-acquired pneumonia.

PMID- 8737128
TI  - Comparative efficacy of sparfloxacin in comparison with amoxycillin plus
      ofloxacin in the treatment of community-acquired pneumonia. French Study Group.
AB  - A prospective, placebo controlled double-blind, randomised study comparing oral
      sparfloxacin 200 mg once daily following a 400 mg loading dose on day 1 with an
      oral combination of amoxycillin 1 g tid plus ofloxacin 200 mg bid was conducted
      in 211 hospitalised patients with community-acquired pneumonia. Patients were
      included in the study if they were aged > 65 years or had failed a previous
      course of antibacterial therapy. The duration of treatment was 10 days. The
      overall efficacy rates for the sparfloxacin and amoxycillin plus ofloxacin
      treatment groups were 91.9% and 81.5%, respectively, in evaluable patients at the
      end of treatment. Age or prior failure of antibacterial therapy did not affect
      the overall success rate of sparfloxacin. The safety profile of sparfloxacin was
      similar to that of the antibacterial combination. This study demonstrated that
      sparfloxacin given once daily is a suitable therapy for the treatment of
      community-acquired pneumonia in the elderly or in patients with failure of
      previous antibiotic therapy.

PMID- 8737129
TI  - Comparative safety and efficacy of sparfloxacin in the treatment of acute
      exacerbations of chronic obstructive pulmonary disease: a double-blind,
      randomised, parallel, multicentre study.
AB  - In a double-blind, placebo-controlled trial, patients with acute exacerbations of
      chronic obstructive pulmonary disease (COPD) were randomly allocated to oral
      treatment with sparfloxacin (200 mg loading dose followed by 100 mg once daily)
      or amoxycillin/clavulanic acid (500 mg/125 mg tds) for a total treatment duration
      of 7 to 14 days. Patients were evaluable if they had a FEV1/FVC ratio of less
      than 70% at stable state and presented with a suspected infectious exacerbation
      defined as increases in dyspnoea, sputum volume and sputum purulence. The primary
      efficacy variable was the overall success (defined as disappearance or
      improvement of dyspnoea and reductions in sputum volume and purulence) at end of
      treatment and follow-up. Overall efficacy was assessed in both the intent-to
      treat (728 patients) and the evaluable (351 patients) populations. At the end of
      treatment and follow-up, success rates were identical for the sparfloxacin (87.3%
      and 78.7%) and amoxycillin-clavulanic acid (88.8% and 79.8%) treatment groups.
      Similar figures were found for the intent-to-treat population. The analysis of
      drug safety was similar for both treatment groups. The most frequently
      encountered pathogens were Streptococcus pneumoniae, Haemophilus influenzae, and
      Moraxella catarrhalis. Sparfloxacin appeared superior for bacteriological
      eradication of Haemophilus influenzae, and Moraxella catarrhalis. Sparfloxacin in
      a single daily dose appears at least as effective as amoxycillin/clavulanic acid
      in the treatment of patients with acute exacerbations of COPD.

PMID- 8737130
TI  - Sparfloxacin versus cefuroxime axetil in the treatment of acute purulent
      sinusitis. Sinusitis Study Group.
AB  - In a double-blind, multicentre trial, 382 patients with a diagnosis of acute
      purulent sinusitis were randomised to receive sparfloxacin 200 mg once daily for
      5 days following a loading dose of 400 mg on day 1 (n = 193) or cefuroxime axetil
      250 mg twice daily for 8 days (n = 189). Patients were classified as success or
      failure according to clinical symptoms plus bacteriological and radiological data
      at the end of treatment and at a follow-up visit. In analyses of the intent-to
      treat (n = 374) and evaluable populations (n = 304), the 5 day course of
      sparfloxacin was at least as effective and well tolerated as the 8 day course of
      cefuroxime axetil. The success rates at the end of treatment in the evaluable
      population were 82.6% and 83.2% in the sparfloxacin and cefuroxime axetil groups,
      respectively. The pathogens isolated most frequently were Haemophilus influenzae
      (33%) and Streptococcus pneumoniae (28%). Response rates according to the
      bacterial aetiology of the acute sinusitis were similar in the two treatment
      groups. Both drugs were well tolerated. The commonest adverse events were
      gastrointestinal and were reported in 2.6% and 3.8% of sparfloxacin- and
      cefuroxime axetil-treated patients, respectively.

PMID- 8737131
TI  - Comparative efficacy and safety of single oral doses of sparfloxacin versus
      ciprofloxacin in the treatment of acute gonococcal urethritis in men.
AB  - A double-blind, randomised, international multicentre study was conducted to
      compare the efficacy and safety of sparfloxacin 200 mg versus ciprofloxacin 250
      mg as single oral-dose treatment for acute gonorrhoea in men. A total of 238
      patients were included and 191 were evaluable for primary efficacy (eradication
      of Neisseria gonorrhoeae). At follow-up, 99% (96/97) of the sparfloxacin-treated
      patients were culture-negative compared with 98% (92/94) in the ciprofloxacin
      group. Three of the four patients who harboured gonococci at follow-up admitted
      to having had unprotected sexual intercourse after treatment and were probably
      reinfections. The rate of post-gonococcal urethritis was 26% in both groups,
      although Chlamydia trachomatis was isolated in only 4% of patients at inclusion.
      Both drugs were well tolerated. Single oral doses of sparfloxacin 200 mg and
      ciprofloxacin 250 mg are equally effective in the treatment of acute gonorrhoea
      in men.

PMID- 8737132
TI  - A comparative study of two different regimens of sparfloxacin versus doxycycline
      in the treatment of non-gonococcal urethritis in men.
AB  - A multicentre, double-blind, randomised study comparing the efficacy and safety
      of oral sparfloxacin (200 mg on day 1 followed by 100 mg daily for 2 or 6
      additional days) with doxycycline (200 mg once daily for 7 days) in the treatment
      of non-gonococcal urethritis in men was conducted. The overall success rates for
      the three treatment groups were statistically equivalent both at the end of
      treatment and at the follow-up visits. For chlamydial urethritis, the rates of
      relapse or possible reinfection were similar in the 7-day sparfloxacin and
      doxycycline groups. For ureaplasmal urethritis and urethritis of unknown
      aetiology, the rates of relapse or possible reinfection were lower in the 7-day
      sparfloxacin group than in the other two treatment groups. Sparfloxacin was well
      tolerated. A 7-day sparfloxacin regimen appears to be a useful alternative to
      doxycycline for the treatment of non-gonococcal urethritis in men.

PMID- 8737133
TI  - Comparative efficacy of sparfloxacin versus ciprofloxacin in the treatment of
      complicated urinary tract infection.
AB  - A total of 686 adult patients with complicated urinary tract infections were
      enrolled in a double-blind, randomised, multicentre study to compare sparfloxacin
      (200 mg loading dose on day 1 followed by 100 mg daily) with ciprofloxacin (500
      mg orally twice daily) for 10 to 14 days. Urinary tract infection was defined as
      pyuria and bacteriuria (cfu > or = 10(5)/mL). Evaluations were performed at four
      time-points. The clinical efficacy of the two antibacterial agents was equivalent
      at the end of treatment: clinical cure in 88.6% of the intent-to-treat population
      and 87.3% in the evaluable population treated with sparfloxacin compared to 85.4%
      and 84.8% of the intent-to-treat and evaluable populations, respectively, treated
      with ciprofloxacin. The clinical results were also equivalent at follow-up. The
      bacteriological efficacy of the two agents was not equivalent. At the end of
      treatment, bacteriological cure was observed in 72.6% of the intent-to-treat and
      72.1% of the evaluable populations treated with sparfloxacin and in 81.4% and
      80.8% of the intent-to-treat and evaluable populations, respectively, treated
      with ciprofloxacin. The difference was primarily because of a higher number of
      persisting pathogens, which included Enterobacteriaceae other than Escherichia
      coli, Pseudomonas aeruginosa and enterococci, which exhibited moderate
      susceptibility to sparfloxacin. Tolerability was similar in the two treatment
      groups.

PMID- 8737134
TI  - Safety profile of sparfloxacin in the treatment of respiratory tract infections.
AB  - A total of 2081 adult patients with community-acquired lower respiratory tract
      infections participated in Phase III clinical trials of sparfloxacin. A total of
      1040 patients were randomised to sparfloxacin and 1041 patients received a
      comparator regimen. Sparfloxacin was administered as a 400 mg loading dose on day
      1 followed by 200 mg once daily to patients with community-acquired pneumonia and
      as a 200 mg loading dose on day 1 followed by 100 mg daily to patients with acute
      exacerbations of chronic obstructive pulmonary disease. Comparator regimens were
      amoxycillin/clavulanic acid 500/125 mg tid, amoxycillin 1000 mg tid, a
      combination of amoxycillin 1000 mg tid plus ofloxacin 200 mg bid or erythromycin
      1000 mg bid. The incidence of adverse events, the incidence and severity of
      antibacterial-related adverse events and the incidence of antibacterial
      discontinuation due to adverse events were no different among patients treated
      with sparfloxacin compared with those who received a comparator antibacterial
      agent. Sparfloxacin appears to be as well tolerated as other oral antibacterial
      regimens commonly used to treat lower respiratory tract infections.

PMID- 8737135
TI  - Overview of electrocardiographic and cardiovascular safety data for sparfloxacin.
      Sparfloxacin Safety Group.
AB  - During the preclinical development of sparfloxacin, prolongation of the
      electrocardiographic QT interval was observed in dogs. Subsequently, the effect
      of sparfloxacin on the QTc interval in man was studied in Phase I studies in
      healthy volunteers. An independent Safety Board was established to evaluate the
      electrocardiograms, provide an assessment of the clinical consequences of
      prolongation of the QT interval, and advise on the design of current and future
      studies. Results of Phase I and Phase III studies have been consistent and
      indicate that the increase in QTc interval associated with sparfloxacin is
      moderate (3% on average) and that patients with renal or hepatic impairment are
      not at increased risk. Few serious adverse cardiovascular events have been
      reported during post-marketing surveillance of sparfloxacin and all have occurred
      in patients with an underlying cardiac condition.

PMID- 8737136
TI  - The Garrod Lecture. Evasion of antibiotic action by bacteria.
AB  - Antibiotics have reduced the mortality from infectious diseases but not the
      prevalence of these diseases. Use, and often abuse, of antimicrobial agents
      encourages the evolution of bacteria toward resistance, often resulting in
      therapeutic failure. This evolution is due to the emergence of "new' resistance
      mechanisms and to the spread of well-characterized mechanisms of resistance to
      the majority of bacterial species. Bacterial resistance can be intrinsic or
      acquired. Intrinsic resistance is species or genus specific and delineates the
      spectrum of activity of the antibiotic. Acquired resistance is present in only
      certain strains of a species or of a genus. The latter results from mutation in a
      gene located in the host chromosome or a plasmid or from acquisition of new
      genetic information by a bacterium, mainly by conjugation or transformation. In
      this review, recent developments in the understanding of biochemical mechanisms
      and the genetics of resistance is considered for the clinically important
      antibiotic families.

PMID- 8737137
TI  - Current therapeutic approaches to cryptosporidiosis in immunocompromised
      patients.
AB  - Cryptosporidium parvum is a protozon which can cause a severe debilitating
      disease in immunocompromised patients. Animal models show that cellular immunity
      is the most important factor protecting against the development of the disease,
      but patients with a humoral immune deficiency are also at risk. In HIV-infected
      patients there is a clear relationship between disease severity and CD4-cell
      counts. The development of insight into the pathogenesis and of new agents is
      hampered by the lack of an in-vitro culture system. Prevention is of utmost
      importance because of the difficulties of therapy and the severity of the
      clinical disease which can develop. Oocysts are highly resistant to the commonly
      used disinfectants. HIV-infected patients with cryptosporidiosis not on
      antiretroviral therapy should commence it. Non-specific therapy with anti
      diarrhoeal agents should be instituted. If no effect is seen, therapy with
      paromomycin 500 mg qds for 2-3 weeks should be started, followed by maintenance
      therapy with 500 mg bid to prevent a relapse.

PMID- 8737138
TI  - pH modulation of aminoglycoside resistance in Staphylococcus epidermidis
      harbouring 6'-N-aminoglycoside acetyltransferase.
AB  - The kinetic constants of the aminoglycoside-modifying enzyme 6'-N-aminoglycoside
      acetyltransferase (AAC(6')IV) from the clinical strain Staphylococcus epidermidis
      RYC 13036 differed depending on whether tobramycin and amikacin (glycosamine
      group) or gentamicin and netilmicin (garosamine group) were used as substrates.
      Acetylation of the glucosamine antibiotics was highly susceptible to substrate
      inhibition which increased with pH whereas the garosamine group compounds showed
      limited substrate inhibition over a wide pH range. These differences in activity
      correlated with MIC values of S. epidermidis RYC 13036 for different
      aminoglycosides. Aminosugars moiety and pH markedly influenced the AAC(6')IV
      aminoglycoside interactions.

PMID- 8737139
TI  - Mutations responsible for reduced susceptibility to 4-quinolones in clinical
      isolates of multi-resistant Salmonella typhi in India.
AB  - Twelve isolates of Salmonella typhi isolated in Vellore, India had reduced
      susceptibility to 4-quinolones (MIC of ciprofloxacin 0.256 mg/L). One isolate was
      isolated in 1992 but the remaining 11 were isolated in 1994. The section of the
      gyrA gene from codons 24 to 185, which includes the "Quinolone Resistance
      Determining Region", was amplified by the polymerase chain reaction and, after
      separating the amplified strands, the DNA was sequenced directly. In the one
      isolate from 1992, no alterations were seen in this region of gyrA, compared with
      the ciprofloxacin-sensitive isolates and presumably decreased 4-quinolone
      susceptibility resulted from reduced permeability of the cell outer membrane or
      another mechanism. In nine isolates from 1994, a substitution of phenylalanine
      for serine at position 83 of GyrA correlated with the decrease in 4-quinolone
      susceptibility. In the remaining two isolates, the novel substitution of
      aspartate to tyrosine at position 87 was found; in one isolate this substitution
      was coupled with another substitution at position 83 but in the other it was not.

PMID- 8737140
TI  - Choice of a routine method for detecting methicillin-resistance in staphylococci.
AB  - Four methods were compared for their abilities to detect methicillin-resistance
      of Staphylococcus strains using mecA gene PCR analysis in 6 h as the gold
      standard. 57 Staphylococcus aureus and 100 coagulase negative staphylococci (CNS)
      were evaluated by the oxacillin disc diffusion method (Kirby-Bauer), the
      automated API (ATB-plus) system (bioMerieux, La Balme les Grottes, France) in 24
      h, the rapid BBL Crystal MRSA ID system (Becton Dickinson, Cockeysville, Md.),
      the oxillin MICs using the NCCLS agar dilution method in 24 h, and the mecA gene
      PCR analysis. For S. aureus, the correlation was excellent between the BBL
      Crystal MRSA ID system and mecA gene PCR analysis (positive predictive value =
      100%; negative predictive value = 97%) and oxacillin MIC (positive predictive
      value = 96%; negative predictive value = 96%). The correlation between BBL
      Crystal MRSA ID and mecA gene PCR was not reliable for CNS (negative predictive
      value = 68%). For CNS, the slower routine susceptibility methods to identify
      intrinsic methicillin-resistance were better: API ATB Staph has a positive
      predictive value = 94% and a negative predictive value = 82%, and the disc
      diffusion test has a positive predictive value = 95% and a negative predictive
      value = 74%. However, BBL Crystal MRSA ID was as reliable as some of the other
      methods tested for CNS after 6 h incubation when the inoculum was increased:
      positive predictive value = 94% and a negative predictive value = 77%. These
      results emphasize that genotypic detection of methicillin-resistance will
      undoubtedly become important to detect rapidly methicillin-resistance, especially
      for CNS.

PMID- 8737141
TI  - Antimicrobial activities in vitro and in vivo of transition element complexes
      containing gold(I) and osmium(VI).
AB  - Metal compounds have been used as antibacterial agents for centuries. The in
      vitro activity of two metal containing complexes, one gold, the other osmium, was
      investigated using a panel of clinically isolated bacteria and Candida albicans.
      Twenty strains of each organism were used and MIC and MBC values determined using
      the agar plate dilution method. Protein binding effects on the activity of the
      compounds were also investigated using media supplemented with 5% human blood. In
      vivo activity of the two compounds was subsequently determined in a hairless
      obese mouse skin-surface activity model. Both compounds were highly active
      against the Gram-positive organisms and Candida albicans in vitro. The gold
      compound had some Gram-negative activity but the osmium complex was inactive
      against these organisms. Both were extensively protein bound. In the in-vivo
      experiment the gold compound achieved a 2-3 log reduction for all the test
      organisms and was at least as good as or superior to mupirocin in its eradication
      rate. The osmium compound was inactive.

PMID- 8737142
TI  - In-vitro and in-vivo antibacterial activity of plaunotol, a cytoprotective
      antiulcer agent, against Helicobacter pylori.
AB  - Recently, some antiulcer agents have been reported to have antibacterial activity
      against Helicobacter pylori, which is highly associated with gastritis and peptic
      ulcers. In-vitro and in-vivo activity of plaunotol, a cytoprotective antiulcer
      agent, against H. pylori was investigated. Antibacterial activity of plaunotol
      against a standard strain (NCTC 11637) and 14 clinical isolates was compared with
      those of other cytoprotective antiulcer agents: benexate, sofalcone, teprenone,
      cetraxate, and gefarnate, by an agar dilution method. The MIC50 and MIC90 of
      plaunotol against 15 strains were 6.25 and 12.5 mg/L, respectively, making it the
      most potent of the cytoprotective antiulcer agents. The bactericidal effect of
      plaunotol was investigated using an in-vitro killing assay. Plaunotol at
      concentrations of more than 6 mg/L induced a rapid reduction of culture
      turbidity, with an extensive loss of viability, within 30 min. Observation by
      scanning electron microscopy revealed that plaunotol caused autolysis and treated
      cells were deformed. In-vivo activity of plaunotol against H. pylori was examined
      in a nude mouse gastritis model. Plaunotol significantly decreased the number of
      H. pylori in the stomach of nude mice. In addition, the antiulcer agent enhanced
      the antibacterial activity of amoxycillin or clarithromycin in the infection
      model.

PMID- 8737143
TI  - In-vitro susceptibility of Klebsiella oxytoca strains to 13 beta-lactams in the
      presence and absence of beta-lactamase inhibitors.
AB  - The susceptibility of Klebsiella oxytoca isolates was tested by an agar diffusion
      method (167 strains collected in six countries) and an agar dilution method (38
      strains). Multivariate analysis of inhibition zone diameters by principal
      component analysis clearly individualised four susceptibility patterns, including
      the phenotype of strains overproducing beta-lactamase and resistant to
      penicillins, first-generation cephalosporins, cefuroxime and aztreonam, but
      susceptible to ceftazidime. This phenotype was different from that conferred by
      plasmid-mediated extended-spectrum beta-lactamases; strains expressing these
      enzymes were also resistant to ceftazidime and cefotaxime. The bla(oxy) gene from
      K. oxytoca was introduced into Escherichia coli and K. oxytoca recipients and
      conferred increased resistance to beta-lactams in the recipient cells. Clavulanic
      acid was effective in association with piperacillin (MIC decreased 36-fold),
      ceftriaxone (35-fold) and aztreonam (19-fold) against overproducing strains, in
      spite of a relatively high IC50 (0.3 microM). Sulbactam (IC50, 400 microM) was
      ineffective in this context when combined with piperacillin (MIC decreased 1.5
      fold), ceftriaxone (1.6-fold) and aztreonam (1.6-fold). The inhibitory activity
      of tazobactam (IC50, 8.2 microM) was heterogeneous depending on the strain and
      the beta-lactam with which it was combined. When combined with piperacillin or
      ceftriaxone little potentiation in antibiotic activity occurred (MIC decreased
      3.9-fold and 4.5-fold, respectively); however, tazobactam plus aztreonam resulted
      in a 50-fold decrease in MIC of antibiotic.

PMID- 8737144
TI  - Effect of pentoxifylline on the course of systemic Candida albicans infection in
      mice.
AB  - Pentoxifylline can decrease the production of tumour necrosis factor alpha (TNF
      alpha) by endotoxin-stimulated macrophages and may improve survival in animals
      with overwhelming bacterial sepsis. In this study various doses of pentoxifylline
      were administered to mice with systemic Candida albicans infection to determine
      its effect on serum TNF alpha levels, organ fungal burden, and host survival.
      Intraperitoneal injections of pentoxifylline at 20 mg/kg every 8 h did not affect
      these endpoints. However, fungal counts were significantly higher in kidneys of
      animals that received 30 and 60 mg/kg of pentoxifylline every 8 h when compared
      to controls. Injection of 60 mg/kg of pentoxifylline at 8 h intervals also
      significantly shortened mean survival from 5.8 to 3.8 days (P = 0.01).
      Pentoxifylline did not affect peripheral WBC counts, serum TNF alpha and
      interleukin-6 levels, or the density of neutrophils in tissues. In vitro,
      pentoxifylline decreased the production of TNF alpha by C. albicans-stimulated
      macrophages in a dose-dependent manner, but only at concentrations greater than
      100 mg/L. In contrast, pentoxifylline suppressed TNF alpha production by
      endotoxin-stimulated macrophages at concentrations as low as 10 mg/L. Thus,
      higher doses of pentoxifylline are detrimental in systemic C. albicans infection.
      However, the detrimental effect is not mediated by alterations in serum TNF alpha
      or interleukin-6 levels or the aggregation of neutrophils in tissues.

PMID- 8737145
TI  - Multiple-dose pharmacokinetics and safety of trovafloxacin in healthy volunteers.
AB  - The multiple-dose pharmacokinetics and safety of trovafloxacin (CP-99,219), a new
      fluoroquinolone antibacterial agent, were evaluated in healthy male volunteers.
      Trovafloxacin was administered orally at 100 or 300 mg as a single dose followed
      by a 3 day washout period, and then was dosed once-daily for 14 consecutive days.
      Multiple serum and urine samples were collected on days 1 and 17 and were
      analysed for trovafloxacin concentrations by HPLC-UV. Following single doses, the
      mean Cmax values (mean +/- S.D.) were 1.0 +/- 0.3 and 2.9 +/- 0.4 mg/L for the
      100 and 300 mg, respectively; those after 14-day consecutive daily dosing (day
      17) were 1.1 +/- 0.2 and 3.3 +/- 0.5 mg/L, respectively. Trovafloxacin was
      rapidly absorbed and reached Cmax approximately 1 h after dosing. The mean values
      of T1/2 associated with the 100 and 300 mg doses were 9.2 +/- 1.2 on day 1 and
      10.5 +/- 0.7 h on day 17; those after the 300 mg doses were 10.5 +/- 1.4 and 12.2
      +/- 1.9 h, respectively. The cumulative urinary recovery of unchanged drug
      averaged 5.3% of the administered dose. Trovafloxacin renal clearance was 0.43 +/
      0.09 L/h. The free fraction of the drug in plasma was 23.8 +/- 6.1%. The renal
      clearance, half-life and unbound fraction did not change over the course of 2
      weeks of multiple dosing. Steady-state serum concentrations were attained by the
      third daily dose, with approximately 1.3-fold accumulation. Both doses of
      trovafloxacin were well tolerated, and no significant changes in any laboratory
      safety parameters were detected. This study shows that the pharmacokinetics of
      trovafloxacin are linear and stationary and that steady-state serum
      concentrations above the MICs for most susceptible pathogens attained.

PMID- 8737146
TI  - Pharmacokinetics of netivudine, a potent anti-varicella zoster virus drug, in
      patients with renal impairment.
AB  - The pharmacokinetics of a single oral 200 mg dose of netivudine (1-(beta-D
      arabinofuranosyl)-5-(1-propynyl)uracil), a nucleoside analogue under development
      for use in varicella zoster virus infections, were studied in 12 renal failure
      (RF) subjects (creatinine clearance 15 +/- 7 mL/min) and 12 age-matched healthy
      subjects with normal creatinine clearance. Blood and urine samples were collected
      up to nine days after drug administration. Concentrations of netivudine and of
      its main metabolite, the pyrimidine base 5-(1-propynyl)uracil (5 PU), were
      determined by a specific high performance liquid chromatography assay. The mean
      peak plasma concentrations of netivudine, Tmax, and volume of distribution were
      not significantly affected by RF. The elimination half-life of netivudine was
      approximately 15 h in subjects with normal renal function and 60 h in RF
      patients. Plasma and renal clearances of netivudine were significantly reduced in
      RF patients and AUC was three to four times higher in these patients. Cmax and
      AUC of 5 PU were higher in RF patients, and the half-life was also significantly
      longer. However, the half-life of this metabolite was much lower than that of the
      parent compound. Tmax and the lag time were similar in the two groups. There were
      highly significant correlations for netivudine and 5 PU between half-life and
      creatinine clearance and between renal clearance and creatinine clearance. These
      findings suggest that netivudine dosage may need to be reduced in patients with
      severe renal failure, and confirm that formation of the 5 PU is independent of
      the elimination of netivudine from plasma.

PMID- 8737147
TI  - A meta-analysis of clinical studies of imipenem-cilastatin for empirically
      treating febrile neutropenic patients.
AB  - There are many clinical studies comparing antibiotic treatments, but the majority
      are too small to have sufficient power to be reasonably certain of detecting
      statistically a moderate treatment effect. For example, few of the 19 studies
      published on imipenem-cilastatin for empirically treating febrile neutropenic
      patients were able to show any significant treatment effect in either direction
      when compared with alternative regimens. We therefore undertook a meta-analysis
      of these studies and made 21 pairwise comparisons of a control regimen with
      imipenem-cilastatin. Eleven comparisons were made between imipenem-cilastatin and
      a beta-lactam-aminoglycoside combination, and a further 10 between the carbapenem
      and a beta-lactam regimen either alone or combined with a glycopeptide or other
      beta-lactam antibiotic. These two data sets were analysed separately. Imipenem
      cilastatin demonstrated a beneficial treatment effect over that achieved by
      aminoglycoside containing control regimens, yielding a typical odds ratio (OR) of
      0.77 (95% CI 0.61 to 0.98). A beneficial treatment effect for the carbapenem
      regimen was also shown against regimens that did not include an aminoglycoside,
      with the typical OR being 0.67 (95% CI 0.54 to 0.84). Although there was clinical
      heterogeneity between studies, the treatment effect itself was relatively
      homogenous. These results show meta-analysis to be a useful aid for interpreting
      the data from clinical studies that are intrinsically too small to provide
      conclusive results.

PMID- 8737148
TI  - Interaction of macrolides with alpha dornase during DNA hydrolysis.
AB  - Since patients with cystic fibrosis are often treated with alpha dornase to
      reduce sputum viscosity, and because of preliminary reports of efficacy of long
      term low-dose erythromycin therapy in chronic airway diseases, it is likely that
      alpha dornase and macrolides might be given together in such patients. A possible
      interaction between these drugs was therefore investigated. Using hyperchromic
      effect to quantify alpha dornase activity, a time- and dose-dependent inhibitory
      effect on human DNA hydrolysis has been observed for erythromycin, roxithromycin
      and azithromycin. Inhibitory doses 50% for alpha dornase were graphically
      determined. Azithromycin exhibited the strongest inhibitory effect.

PMID- 8737149
TI  - The effect of rifampicin on adaptive resistance of Pseudomonas aeruginosa to
      aminoglycosides.
AB  - Using the dynamic chequerboard technique, we confirmed that rifampicin produces a
      synergistic bactericidal effect when combined with amikacin or netilmicin.
      Adaptive resistance was suppressed when rifampicin was added to aminoglycoside
      after, but not during, first exposure to amikacin or netilmicin. The effect of
      rifampicin on adaptive resistance could account for the synergy between
      rifampicin and aminoglycosides.

PMID- 8737150
TI  - Evaluation of the Etest for rapid susceptibility testing of Mycobacterium avium
      to clarithromycin.
AB  - MICs of clarithromycin were determined by the Etest method for thirty clinical
      strains of Mycobacterium avium complex (MAC) and compared with MICs results as
      determined by the reference agar dilution method. Agreement (within +/- 1 log2
      dilution) between the Etest and the reference method was 70% for susceptible
      strains and 100% for resistant strains. No major errors resulting in
      misclassification in susceptibility or resistance categories were detected for
      the Etest MIC method. It is suggested that the Etest is easy to perform and is an
      accurate method for determining susceptibility of MAC strains to clarithromycin.

PMID- 8737151
TI  - In-vitro activity of psychiatric drugs against Corynebacterium urealyticum
      (Corynebacterium group D2).
AB  - We tested the in-vitro activity of amoxycillin, amoxycillin/clavulanic acid,
      cefotaxime, gentamicin, trimethoprim-sulphamethoxazole, tetracycline,
      norfloxacin, ciprofloxacin, vancomycin, teicoplanin, clindamycin and five
      psychiatric drugs (chlorpromazine, sertraline, fluoxetine, paroxetine and
      risperidone) against 32 strains of Corynebacterium urealyticum. Resistance rates
      exceeded 90% for all antibiotics except glycopeptides, quinolones and
      tetracycline. Sertraline was the most active psychiatric drug. We tested the
      influence of sertraline on the activity of amoxycillin, amoxycillin/clavulanic
      acid, cefotaxime, gentamicin, trimethoprim-sulphamethoxazole, tetracycline and
      ciprofloxacin. We did not observe antagonism in any case. Sertraline enhanced the
      activity of ciprofloxacin and tetracycline against all strains (MIC decrease: 4
      64-fold for ciprofloxacin, 2-32-fold for tetracycline).

PMID- 8737152
TI  - Comparative in-vitro activity of the new fluoroquinolone trovafloxacin (CP
      99,219) against gram-positive cocci.
AB  - The in-vitro activities of the new fluoroquinolone trovafloxacin (CP-99,219) and
      ciprofloxacin were determined against 225 Gram-positive cocci. Trovafloxacin was
      4-32 fold more active than ciprofloxacin against staphylococci and streptococci
      and also showed greater activity against enterococci including vancomycin
      resistant Enterococcus faecium and Enterococcus faecalis that were highly
      resistant to aminoglycosides and/or produced beta-lactamase. Trovafloxacin was
      also bactericidal at 3 mg/L against enterococci except for isolates for which the
      MICs were > or = 2 mg/L.

PMID- 8737153
TI  - Concentration of teicoplanin in the serum of adults with end stage chronic renal
      failure undergoing treatment for infection.
AB  - We examined the adequacy of the following schedule for the administration of i.v.
      teicoplanin to patients with chronic renal failure: three doses of 6 mg/kg at 12
      h intervals, a fourth dose 24 h later and then subsequent doses every 72 h. Eight
      infected patients undergoing dialysis were investigated, with serum antibiotic
      concentrations measured ten minutes before and one hour after administration.
      Mean trough concentrations were 6.9 +/- 3.1 mg/L on day two, 9.8 +/- 4.4 mg/L
      (day three), 9.2 +/- 4.8 mg/L (day six), 10.9 +/- 5.5 mg/L (day nine), 12.1 +/-
      6.1 mg/L (day 12) and 14.8 +/- 8.0 mg/L (day 15). The proposed schedule achieved
      adequate trough serum teicoplanin concentrations by 48 h in six out of eight
      patients examined. The dosage regimen was well tolerated.

PMID- 8737155
TI  - Over-the-counter antimicrobials: the hidden costs of resistance.

PMID- 8737154
TI  - Safe intravenous antibiotic therapy at home: experience of a UK based programme.
AB  - Outpatient i.v. antibiotic therapy is well developed in the United States,
      largely because of pressures from third-party payers to reduce costs of medical
      care. We have developed an outpatient i.v. antibiotic programme in Oxford, that
      has evolved from a desire to provide high quality i.v. therapy to AIDS patients
      with cytomegalovirus retinitis. We describe the rationale of the service and
      report on our first two years' experience. We treated 67 consecutive patients
      (eight with HIV infection) at home with i.v. antibiotics. This resulted in a
      saving of 2275 hospital days for those patients without HIV infection. HIV
      positive patients received 69 months of home i.v. therapy. Minor intravascular
      catheter complications occurred in only five patients (7.5%). The only serious
      complications were three episodes of catheter-related sepsis (4.5%), all
      occurring in AIDS patients who had lines in for more than six months. We have
      shown that home i.v. antibiotic therapy can be delivered safely to patients with
      a wide variety of infectious problems using the existing network of community
      nurses in the National Health Service. Essential components to the programme
      include a multidisciplinary team working between the hospital and community and a
      written shared care protocol. Such a programme can result in reduced lengths of
      hospital stay and patient, community nurse and physician satisfaction.

PMID- 8737156
TI  - gyrA of ofloxacin-resistant clinical isolates of Mycobacterium tuberculosis from
      Hong Kong.

PMID- 8737157
TI  - Comparative stability of carbapenem and penem antibiotics to human recombinant
      dehydropeptidase-I.

PMID- 8737158
TI  - Pneumococcal susceptibility to meropenem.

PMID- 8737159
TI  - In-vitro activity of cefditoren against clinical isolates of penicillin
      susceptible and resistant strains of Streptococcus pneumoniae, Haemophilus
      influenzae and Neisseria meningitidis.

PMID- 8737160
TI  - Cystitis due to vancomycin-intermediate Staphylococcus saprophyticus.

PMID- 8737161
TI  - Pharmacokinetics of once-daily versus thrice daily tobramycin in cystic fibrosis
      patients.

PMID- 8737162
TI  - Fluconazole plus allopurinol in treatment of visceral leishmaniasis.

PMID- 8737163
TI  - Food and general neophobia in Swedish families: parent-child comparisons and
      relationships with serving specific foods.
AB  - The aims were to investigate the occurrence of food and general neophobia in
      Swedish families with children 2-17 years of age, parent-child correlations with
      respect to neophobia and the relationships between neophobia and the reported
      serving of specific foods in the family. A group of 370 randomly selected
      families from two Swedish towns (stratified, 185 from each) were invited and 57
      (15%) participated. The results are based on the Food and General Neophobia
      Scales (Pliner & Hobden, 1992), parental ratings of child food neophobia and an
      ad hoc Food Frequency Questionnaire. The overall levels of neophobia were
      relatively low for both children and parents. There were only a few significant
      gender differences with respect to Food Neophobia but fathers and boys scored
      numerically higher than did mothers and girls on several items in the Food
      Neophobia Scale. The children, particularly boys, showed significantly higher
      Food and General Neophobia than their parents. Both Food and General Neophobia
      tended to decrease with increasing age among the children. Families were divided
      according to whether specific foods had been served or not. This classification
      showed virtually no relationship with the degree of food neophobia of family
      members. However, the higher the food neophobia in mothers and children, the
      fewer of the listed uncommon foods had been served in the family.

PMID- 8737164
TI  - Influences of gender, amount of food, and speed of eating on external raters'
      perceptions of binge eating.
AB  - Traditional methods for examining binge-eating (e.g. food diaries, laboratory
      binges), primarily employing clinical samples, have a number of limitations. This
      paper details three studies utilizing a new methodology to examine perceptions of
      binge eating: standard videotapes of male and female models consuming doughnuts.
      College students (n = 459) viewed one of nine videotapes and were asked if the
      eating behavior of the model was a binge or not. Variables manipulated include
      gender of the model, number of doughnuts, rate of eating and social (vs.
      solitary) eating. The number of doughnuts eaten by a female model was sufficient
      for female subjects to label it as a binge. In order for a male to have binged,
      females responded to the amount; males required both speed and amount. Results
      are discussed in terms of their relevance for understanding perception of binge
      eating in normal and clinical populations.

PMID- 8737165
TI  - Effects of effort and social modeling on drinking in humans.
AB  - The role of economic and social influences on water intake in humans was explored
      in two experiments. In the first experiment, the effect of water cost (as defined
      as the amount of effort required to acquire water) on prandial drinking was
      studied by manipulating water position during an ad libitum meal: water was
      available either on the dining table, about 20 feet from the table, or
      approximately 40 feet away. Subjects drank significantly more when the water was
      on the table than in the other conditions; but a linear relationship between cost
      (distance) and intake was not observed. In the second experiment, the effects of
      water cost and a social model on drinking were assessed in a similar paradigm.
      Increasing effort required to obtain water significantly reduced prandial water
      intake, and the presence of a social model increased water intake. Although some
      interesting trends emerged, no significant interactions between social and
      economic factors were found. These experiments demonstrate that environmental
      factors can significantly affect facultative drinking in humans.

PMID- 8737166
TI  - Effects of weight and energy content of preloads on subsequent appetite and food
      intake.
AB  - This study was done to determine the relative effects of energy content and
      weight of ingested food on subsequent satiety and food intake. The weight/volume
      and the energy content of nine preloads were manipulated, in a 3 x 3 factorial
      design, to give three weight levels, 250, 500 and 750 g, and three energy levels
      0, 1.26 and 2.51 MJ (0, 300 and 600 kcal). The weights were varied by the
      addition of water, while the energy levels were varied by using yogurt and cream.
      Each of the 1.26 and 2.51 MJ preloads contained 27 g of protein and 31 g of
      carbohydrates. The 1.26 MJ preloads contained 8 g of fat and the 2.51 MJ preloads
      had 41 g of fat. Each of the nine preloads was presented as a lunch to 21 female
      and 16 male subjects. Two hours after the preloads, subjects consumed sweet and
      savory snacks and various drinks ad libitum from a buffet. The weight of the
      preload had a small but statistically significant effect on feelings of hunger
      and satiety between preload and buffet, and on energy intake during the buffet
      (5.34, 5.05 and 5.04 MJ after 250, 500 and 750 g preloads). There was a large
      difference between 0 and 1.26 MJ, but little difference in effect between 1.26
      and 2.51 MJ preloads. Mean energy intakes in the buffet after the 0, 1.26 and
      2.51 MJ preloads were 6.17, 4.83 and 4.42 MJ. These results suggest that the
      weight or amount of food affects subsequent appetite and food intake, but the
      effect of energy is stronger.

PMID- 8737167
TI  - Energy density and its role in the control of food intake: evidence from
      metabolic and community studies.
AB  - This review discusses the role that dietary composition and energy density play
      in the control of eating behaviour. The effect of dietary manipulations of fat
      and carbohydrate on energy intake remains controversial. We suggest this to be
      largely a consequence of different study designs. When low-fat foods are included
      in the diet and thus only some items manipulated subsequent food choice commonly
      ensures compensation and energy intake remains constant. However, when all items
      are manipulated and macronutrient composition fixed, an alteration in the energy
      density results in a parallel change in energy intake and there is no energy
      compensation. In addition, we hypothesise that hyperphagia on high-fat diets is a
      consequence of a high energy density rather than fat content per se. Independent
      of fat content, low energy dense diets generate greater satiety than high energy
      dense diets, suggesting that an important regulatory signal may be the weight or
      volume of food consumed. Epidemiological studies confirm that energy intake
      increases with energy density and thus weight loss may be best achieved on a low
      energy dense diet. Although the use of low-fat items may not reduce intake during
      covert manipulation, it may be successful during periods of deliberate dieting,
      providing that food-substitutions are not counter-balanced by other high density
      items.

PMID- 8737168
TI  - Acid-base balance affects dietary choice in cats.
AB  - The effect of acid-base status on self-selection of dietary protein was examined
      in three groups of adult male cats fed 20% soybean-protein and lactalbumin diets
      formulated to produce acidic, neutral or alkaline status. In two experiments,
      cats were offered a choice between the 20% protein diets or (1) the same diet
      with additional protein as casein (49% total crude protein) or (2) the same diet
      with added soybean-protein and lactalbumin (43% crude protein). Casein contained
      0.63 mmol H+/g and caused all three groups to avoid the high casein diets by day
      4. The high soybean-protein-lactalbumin diets did not contain added acid but
      would produce some extra acid upon catabolism of the sulfur-containing amino
      acids. Again, all three groups avoided the high protein diets by day 4. In a
      third choice trial, cats adapted to three low protein diets containing
      appropriate electrolytes to cause neutrality, acidemia or alkalemia, were offered
      a choice between: neutral vs. acidic; acidic vs. neutral or basic vs. acidic. The
      cats chose the neutral, neutral and basic diet respectively, restoring or
      maintaining acid-base homeostasis for each situation. The diets producing
      acidosis lowered serum sodium and potassium concentrations. We conclude that cats
      select appropriate diets in an attempt to maintain acid-base homeostasis.

PMID- 8737169
TI  - Effects of stressful noise on eating and non-eating behavior in rats.
AB  - Eating and other behaviors were measured in 36 food-deprived rats on 15
      consecutive days during 20 min test sessions. During training sessions 1 to 5 all
      animals were habituated to the test boxes with white noise of 55 dB intensity.
      For sessions 6 to 10 noise intensity was increased to 95 dB for the experimental
      rats and to 60 dB for the control rats. The food intake of experimental rats was
      lower for stress session 1. The duration of eating behavior was lower, and
      durations of exploring, grooming and resting behaviors were higher for all stress
      sessions for rats exposed to 95 dB white noise. Speed of eating behavior was
      higher for all stress sessions in the experimental group. Defecation rate of the
      experimental rats was higher for all stress sessions. On post-stress sessions 11
      to 15 animals were again tested under the stimulus conditions of the training
      period (55 dB). No significant effects were observed for this period. The results
      are discussed with respect to models of "stress-induced" eating and behavioral
      ecology.

PMID- 8737170
TI  - Changes in the distribution of a calcium-dependent ATPase during demyelination
      and remyelination in the central nervous system.
AB  - A calcium-adenosine triphosphatase (Ca(2+)-ATPase) activity expressed by CNS
      nerve fibres has been examined during demyelination and remyelination in rats, 21
      26 days after an intraspinal injection of ethidium bromide. The Ca(2+)-ATPase
      distribution was determined cytochemically, using a technique believed primarily
      to reflect the presence of ecto-ATPases. We confirm that in normal nerve fibres
      Ca(2+)-ATPase activity was present on the external surface of the myelin sheath,
      and on the axolemma at the nodes of Ranvier. Labelling of the internodal axolemma
      was restricted to small, scattered, punctate regions. However, following
      demyelination the Ca(2+)-ATPase activity was expressed continuously along both
      the exposed, previously internodal axolemma of entirely naked axons, and it was
      particularly prominent at sites of contact between axons and glial-cell
      processes. During remyelination (which in this lesion is accomplished
      predominantly by Schwann cells) the proportion of the axonal surface exhibiting
      Ca(2+)-ATPase activity decreased in concert with the progressive thickening of
      the new myelin sheath. The non-myelin forming plasmalemma of Schwann cells was
      positive for the Ca(2+)-ATPase activity, but activity was abruptly lost at the
      site of compaction between the inner and outer leaflets of the forming myelin
      sheath. Ecto-ATPase activity is a property of some cell adhesion molecules, and
      it follows that the changes observed in the distribution of ATPase activity in
      this study may reflect changes in the axolemma which are important for the
      successful repair of the lesion by remyelination. The ATPase activity may, for
      example, reflect the changing distribution of molecules important in aiding axo
      glial recognition and the establishment of axo-glial contacts.

PMID- 8737171
TI  - Compartmentation of alpha-internexin and neurofilament triplet proteins in
      cultured hippocampal neurons.
AB  - Intermediate filaments comprise an integral part of the neuronal cytoskeleton.
      However, little is known about their function, and there remains some uncertainty
      about their precise subcellular localization. We examined the timing of
      expression and distribution of alpha-internexin, neurofilament triplet proteins
      and peripherin using immunocytochemistry in cultured hippocampal neurons. alpha
      Internexin immunostaining was present in all neurons at all developmental stages.
      Immunostaining appeared as long filaments in axons and short fragments in
      dendrites which extended into dendritic spines. The presence of alpha-internexin
      in dendritic spines was confirmed in situ by electron microscopy of rat
      hippocampal tissue sections and suggests that this intermediate filament may
      serve as a link between cytoskeletal elements in dendritic shafts and spines. In
      culture, immunostaining using antibodies against individual triplet protein
      subunits indicated that light (NF-L) and middle (NF-M) subunits were first
      expressed in cells shortly after the initiation of axonal outgrowth. Expression
      of the heavy (NF-H) subunit occurred a few days later. Although timing and
      localization of expression did not correlate with the initiation of axonal or
      dendritic processes, it was coincident with periods of rapid outgrowth. Triplet
      proteins were more abundant in axons and appeared to be incorporated into
      lengthier filaments than in dendrites. Highly phosphorylated NFH/M
      immunoreactivity was polarized to axons after 6 days in culture. The distribution
      of one NF-H epitope was restricted to GABAergic neurons in mature cultures,
      suggesting a cell-type specific modification. Peripherin was not detectable at
      any time in hippocampal cultures. Our results show that intermediate filaments
      are integral components of the neuronal cytoskeleton of cultured hippocampal
      neurons throughout development. Furthermore, the localization of alpha-internexin
      suggests that it may be involved in the formation or maintenance of dendritic
      spines.

PMID- 8737172
TI  - Carotid sinus nerve terminals which are tyrosine hydroxylase immunoreactive are
      found in the commissural nucleus of the tractus solitarius.
AB  - Tyrosine hydroxylase immunoreactive sensory neurons in the petrosal ganglion
      selectively innervate the carotid body via the carotid sinus nerve. Central
      projections of the carotid sinus nerve were traced with horseradish peroxidase.
      The commissural nucleus of the tractus solitarius was examined by dual labelling
      light and electron microscopy. Dense bilateral labelling with horseradish
      peroxidase was found in the tractus solitarius and commissural nucleus of the
      tractus solitarius. Horseradish peroxidase was found in unmyelinated axons,
      myelinated axons, and nerve terminals. About 88% of horseradish peroxidase
      labelled carotid sinus nerve axons were unmyelinated. Tyrosine hydroxylase
      immunoreactivity was identified in unmyelinated axons, myelinated axons,
      dendrites, perikarya, and nerve terminals. Most tyrosine hydroxylase
      immunoreactive axons (93%) in the commissural nucleus of the tractus solitarius
      were unmyelinated. Tyrosine hydroxylase immunoreactivity was simultaneously
      identified in carotid sinus nerve unmyelinated axons, myelinated axons, and nerve
      terminals. These double-labelled terminals comprised 28% of the number of
      tyrosine hydroxylase immunoreactive terminals in the commissural nucleus of the
      tractus solitarius, and 55% of transganglionically-labelled terminals. Therefore,
      there are both central and peripheral sources of tyrosine hydroxylase
      immunoreactive nerve terminals in the commissural nucleus of the tractus
      solitarius. These data support the hypothesis that peripheral tyrosine
      hydroxylase immunoreactive neurons are involved in the origination of the
      chemoreceptor reflex. Axo-axonic synapses between peripheral carotid sinus nerve
      afferent terminals and central terminals containing tyrosine hydroxylase
      immunoreactivity were observed in 22% of the axo-axonic synapses observed. Thus,
      central tyrosine hydroxylase immunoreactivity neurons are involved in the
      modulation of the chemo-and/or baroreceptor reflexes. Synaptic contacts were not
      observed between carotid sinus nerve afferents and tyrosine hydroxylase
      immunoreactive perikarya of dendrites. Catecholaminergic neurons are thus
      unlikely to be the second order neurons of either the chemo-or baroreceptor
      reflex in the commissural nucleus of the tractus solitarius.

PMID- 8737173
TI  - An immuno-electronmicroscopical study of the distribution of laminin within
      autografts of denatured muscle.
AB  - We have used an immunogold post-embedding technique to examine, qualitatively and
      quantitatively, the distribution of laminin along sarcolemmal basal laminae of
      variously treated muscle autografts placed in transected rat sciatic nerves. We
      found that freeze-thawing or heating to 60 degrees C prior to grafting did not
      affect laminin labelling density along the sarcolemmal basal laminae, either at
      the time of preparation or 7 days after grafting. In sharp contrast, heating to
      80 degrees C significantly reduced laminin labelling density. These findings are
      consistent with our earlier work showing that frozen-thawed or 60 degrees C
      muscle autografts both support axonal regeneration, whereas 80 degrees C grafts
      do not, and add further support to the view that laminin is a functionally
      important molecule in nerve regeneration. We have compared immunostaining using
      10 nm gold particles with silver enhancement of 5 nm gold particles: although
      labelling density was higher in the silver-enhanced preparations, there was no
      increase in background labelling. Although empty sarcolemmal basal lamina tubes
      were frequently highly infolded, there was no evidence of preferential labelling
      of either 'peaks' or 'troughs' of the infolded basal laminae.

PMID- 8737174
TI  - Sciatic nerve injury in the adult rat: comparison of effects on oligosaccharide,
      CGRP and GAP43 immunoreactivity in primary afferents following two types of
      trauma.
AB  - Using immunocytochemical and morphometric techniques, the localisation of three
      neuronal oligosaccharide antigens (two lactoseries and one globoseries
      oligosaccharide) were studied in the spinal cord and dorsal root ganglia of adult
      rats following unilateral crushing or transection of the sciatic nerve. The
      expression of CGRP and GAP43 was also studied for comparison. We found that
      following transection of the nerve the expression of lactoseries oligosaccharides
      and CGRP was permanently depressed, whilst that of the globoseries antigen
      (SSEA4) was unaffected. However following crush trauma and subsequent
      regeneration after 2 months, only the expression of one lactoseries antigen, LA4
      remained significantly depressed. Our results suggest that different subsets of
      sensory neurons vary in the rate of reaction to injury and that one subset of
      neurons expressing a lactoseries oligosaccharide antigen is particularly
      susceptible to axotomy-induced changes. Furthermore neurons expressing the
      globoseries oligosaccharide antigen SSEA4 appear to be relatively unaffected by
      peripheral axotomy.

PMID- 8737175
TI  - Pill or people?--the choice is ours.

PMID- 8737176
TI  - The effect of concomitant use of neuroleptic drugs and lithium on the
      erythrocyte/plasma lithium ratio in Iranian patients with bipolar disorder.
AB  - Patients treated with lithium (Li+) and neuroleptic drugs concomitantly are
      reported to show more pronounced adverse effects than patients on Li+ alone.
      There are conflicting results about the effect of neuroleptic drugs on the
      erythrocyte/plasma Li+ ratio and intraerythrocyte Li+ concentration, and
      methodological problems may be a reason for this. The effect of the concurrent
      use of neuroleptic drugs with Li+ on the Li+ ratio was studied in 66 patients
      with bipolar affective disorders during prophylactic Li+ therapy using the new
      direct method of measuring erythrocyte Li+ concentration. This new direct method
      has been shown to give much more precise and accurate results than the values
      obtained by other methods. No relationship was found between the Li+ ratio and
      sex, age, Li+ dosage, duration of treatment or plasma Li+ concentration. Results
      revealed that patients taking a combination of Li+ and neuroleptic drugs showed
      significantly lower Li+ ratios and intraerythrocyte Li+ concentrations as
      compared with those on Li+ alone. It is notable that this reducing effect of
      neuroleptic drugs was increased by the concurrent use of two types of neuroleptic
      drugs. The effect on neuroleptic drugs on the Li+ ratio may be mediated through a
      stabilizing effect of these drugs on the cell membrane and consequently Li+
      transport in erythrocytes.

PMID- 8737177
TI  - In-line filter occlusion during intravenous delivery of injectable menatetrenone
      (vitamin K2).
AB  - Filter occlusion during intravenous infusion of injectable menatetrenone in an
      electrolyte fluid was examined. The menatetrenone concentration and its emulsion
      droplet size were not changed by in-line filtration. However, particle counts in
      the admixed solution and examination of scanning electron micrographs of the
      surface of the filter membrane indicated that particle formation occurred
      immediately after the admixture of menatetrenone injection with Hicaliq No. 2,
      but not with 5% glucose injection. This may be due to the interaction of excess
      lecithin in the emulsion with the electrolyte. Filter occlusion also occurred
      with the admixture of menatetrenone-free emulsion and Hicaliq No. 2, but not with
      5% glucose injection. These findings indicate that injectable menatetrenone
      should not be admixed with electrolyte fluids.

PMID- 8737178
TI  - Pleural effusion associated with D-penicillamine therapy: a case report.
AB  - This case report illustrates the occurrence of a large pleural effusion
      associated with long-term D-penicillamine therapy. This complication has not
      previously been reported.

PMID- 8737179
TI  - Long-term stability of cimetidine in total parenteral nutrition.
AB  - The stability of cimetidine (Tagamet) was investigated in total parenteral
      nutrition (TPN) mixtures containing different amino acid sources. TPN mixtures
      were stored at 5 degrees C in ethylvinyl acetate bags for 28 days and analysed by
      stability-indicating high-pressure liquid chromatography. Results indicated that
      cimetidine was physically compatible and chemically stable (less than 5%
      degradation) for at least 28 days in TPN mixtures containing either Freamine III,
      Vamin 14 or Aminoplex 12 as the amino acid source.

PMID- 8737180
TI  - Demonstrating effectiveness--the concept of numbers-needed-to-treat.
AB  - When assessing a health-care intervention the main question is--does it work?
      Often, a more difficult question needs to be answered--how well does it work?
      Systematic reviews and meta-analyses help to provide answers to both questions.
      Too often though, the results are expressed in a way that leaves the reader
      asking, 'what is the result?' Numbers-needed-to-treat is a simple method for
      conveying the answers. It can be applied to any chosen clinical outcome with
      dichotomous data, and the results can be understood by doctor, patient and the
      public. This paper discusses the concept of numbers-needed-to-treat and gives
      worked examples using trials in H. pylori eradication and lowering of serum
      cholesterol.

PMID- 8737181
TI  - Frequency of thyroid disease among Southeast Asian primary care patients.
AB  - We prospectively assessed 99 Southeast Asians for the presence of thyroid disease
      who were attending a primary care clinic devoted to the care of refugees.
      Subjects were undergoing evaluation as new patients and had no previously
      diagnosed thyroid abnormality. Each patient had a physical examination performed
      by his or her primary-care provider, was given a standardized questionnaire that
      focused on symptoms of thyroid disease and underwent a venipuncture for total
      thyroxine, triiodothyronine resin uptake and thyrotropin (TSH) concentration.
      Those who had an abnormal examination, calculated free thyroxine index (FT4I) or
      TSH level were re-examined by an endocrinologist and had repeat thyroid studies
      performed. Although 81% of patients reported > or = 1 symptom compatible with
      thyroid dysfunction, only 17% were found to have laboratory abnormalities. An
      abnormal FT4I and TSH level was found in 5% and 13% of subjects, respectively,
      but only one case of clinically significant hyperthyroidism and no cases of
      hypothyroidism were confirmed. TSH suppression, noted in 12% of subjects,
      persisted over a median follow-up of 6 months. Among seven patients with an
      anatomic abnormality of the thyroid, four had an abnormal FT4I or TSH. We
      conclude that the clinical prevalence of symptomatic thyroid dysfunction among
      Southeast Asians is comparable to that reported for non-Asian populations, but
      that the frequency of subclinical hyperthyroidism may be higher. Although
      symptoms suggestive of thyroid disease are common, routine screening for thyroid
      disease is not indicated in this study.

PMID- 8737182
TI  - The causes and management of atrial fibrillation.
AB  - Atrial fibrillation is present in approximately 10% of the population aged over
      65 years, in whom its presence is associated with a significantly increased
      morbidity and mortality. Principal complications include reduced cardiac output
      and the precipitation of heart failure and thromboembolic phenomena, including
      strokes and peripheral emboli. In the majority of cases atrial fibrillation is
      associated with ischaemic heart-disease and hypertension. Other important causes
      are thyrotoxicosis, valvular heart-disease and atrial septal defect. The primary
      aims of treatment in atrial fibrillation are to terminate the arrhythmia
      (cardioversion) with either drugs or direct current (DC) shock and to prevent its
      recurrence. Effective cardioversion may necessitate the treatment of underlying
      pathology. If these primary aims cannot be achieved then an attempt must be made
      to effectively control the ventricular rate with drugs such as digoxin. Recently,
      further strong evidence has been provided to support the role of anticoagulants
      and antiplatelet drugs in preventing the major problem of systemic thromboembolic
      complications. Some of the special difficulties relating to the treatment of
      atrial fibrillation associated with thyrotoxicosis as well as paroxysmal atrial
      fibrillation will also be considered.

PMID- 8737183
TI  - The impact of clinical pharmacy intervention in a psychiatric hospital.
AB  - One hundred and nine physician-initiated consultations were directed to a
      clinical pharmacist over a 1-year period. Two hundred and three (88.2%)
      recommendations out of 229 were adopted. Major question types included preventive
      measures, non-response, side-effects and mixed factors. The global effectiveness
      of pharmacist interventions suggests that 67.9% of patients exhibited a very
      satisfactory or satisfactory response. While our study suggests that a clinical
      pharmacist may favourably contribute to the quality of patient care, a control
      group study is required to confirm our results.

PMID- 8737184
TI  - Near-patient stability studies.
AB  - Approaches to performing stability tests on formulations developed in hospitals,
      defined as the near-patient situation, are reviewed. Emphasis is placed on the
      selection and validation of storage conditions and the statistical methodology
      necessary to ensure confidence in the results obtained.

PMID- 8737185
TI  - Consensus development meeting 1995: combined oral contraceptives and
      cardiovascular disease. The Consensus Statement issued after the Second European
      Conference on Sex Steroids and Metabolism, Amsterdam, November 1995. Writing
      Committee.

PMID- 8737186
TI  - No difference between micro- and macroprolactinomas in the prolactin
      responsiveness to metoclopramide and dopamine administration.
AB  - Differences between micro- and macroprolactinomas, as regards the prolactin
      secretory pattern in response to pharmacological challenges, have been reported
      in in vivo and in vitro models, and interpreted as being due to different
      dopaminergic regulation of prolactin release. In 32 patients with prolactin
      secreting tumors, 19 with microprolactinomas and 13 with macroprolactinomas, and
      ten healthy volunteers, we evaluated the prolactin secretion in response to
      pharmacological manipulations of central dopaminergic tone. To this end, three
      tests were performed, in random order: (1) 4-h saline infusion; (2) 10 mg
      metoclopramide as i.v. bolus; (3) 4-h dopamine infusion (0.01 microgram/kg/min)
      with a 10-mg metoclopramide bolus given after the second hour of infusion.
      Dopamine infusion, compared to saline, caused a significant prolactin decrease in
      all the three groups of subjects, without significant difference between micro-
      and macroprolactinoma patients. In prolactinoma patients, administration of
      metoclopramide induced a significant rise in plasma prolactin which, however, was
      significantly lower than the one displayed by controls. Again, no difference was
      observed between the two groups of hyperprolactinemic patients. Dopamine infusion
      induced a significant and comparable increase in the prolactin response to
      metoclopramide in micro- and macroprolactinoma patients, while it was ineffective
      in control subjects. In conclusion, no differences appear to exist between micro-
      and macroprolactinoma patients as regards the prolactin secretory pattern during
      pharmacological modifications of the dopaminergic tone. A central dopaminergic
      defect and an increased prolactin turnover with attendant reduction of the
      intracellular hormone pool may both be involved in the reduced prolactin release
      following provocative stimuli in patients with prolactinoma.

PMID- 8737187
TI  - Superovulation with urinary human follicle-stimulating hormone: correlations with
      body mass index and body fat distribution.
AB  - Our objective was to investigate the relationship between body mass index (BMI),
      waist/hip ratio (WHR), follicle-stimulating hormone (FSH) dose, length of
      stimulation and clinical outcome in infertile women with and without polycystic
      ovary syndrome (PCOS) undergoing controlled ovarian hyperstimulation. Controlled
      ovarian hyperstimulation was induced in 60 women for a total of 111 cycles (48%
      in PCOS patients) with urinary human FSH (u-hFSH). A significant correlation
      between BMI, u-hFSH dose and duration of stimulation was found in PCOS and non
      PCOS patients with WHR < 0.8. These correlations were not present in PCOS
      patients with WHR > 0.8. Pregnant patients received significantly less ampules of
      u-hFSH. From our data we suggest a controlled ovarian hyperstimulation protocol,
      for obese non-PCOS patients and obese PCOS patients with WHR < 0.8, starting with
      a double dose of u-FSH.

PMID- 8737188
TI  - A prospective pilot study of co-treatment with growth hormone and gonadotropins
      for improving spermatogenesis in normogonadotropic patients with severe
      oligoteratoasthenospermia.
AB  - The objective of this study was to induce spermatogenesis by co-treatment with
      growth hormone and gonadotropins in normogonadotropic patients with severe
      oligoteratoasthenospermia (OTA) who had failed to respond adequately to
      conventional therapy. A prospective study in which co-treatment with growth
      hormone (4 IU) and human menopausal gonadotropin (hMG; 150 IU of follicle
      stimulating hormone (FSH) and 150 IU of luteinizing hormone (LH)), three times a
      week, and human chorionic gonadotropin (hCG; 2500 IU), two times a week for 24
      weeks, were administered after unsuccessful treatment for at least 12 weeks with
      gonadotropins. Four patients who had failed to respond to conventional treatment
      with gonadotropins participated in the study. Semen volume, sperm production,
      serum testosterone, LH, FSH, insulin-like growth factor-I (IGF-I) and growth
      hormone-binding protein concentrations were used to measure outcome. In all four
      patients, there was no improvement in sperm quality as compared to baseline
      measurements. Serum testosterone concentrations remained within normal limits. A
      significant increase in both serum IGF-I and growth hormone-binding protein was
      found following treatment with growth hormone. Our results do not encourage the
      use of co-treatment of gonadotropins with growth hormone in cases of
      normogonadotropic OTA syndrome patients who fail to respond adequately to the
      conventional therapy with gonadotropins.

PMID- 8737189
TI  - Successful induction of spermatogenesis in a patient with hypogonadotropic
      hypogonadism following co-treatment with growth hormone.

PMID- 8737190
TI  - A three-year clinical investigation into efficacy, cycle control and tolerability
      of a new low-dose monophasic oral contraceptive containing gestodene.
AB  - This long-term, open-label multicenter study investigated the clinical efficacy
      and tolerability of a monophasic oral contraceptive containing 20 micrograms
      ethinylestradiol and 75 micrograms gestodene. A total of 670 women between the
      ages of 18 and 45 years received the trial preparation over a 3-year period,
      giving 19,095 evaluable cycles. Of the 670 participants in the study, 75%
      completed at least 24 cycles with the trial preparation and 46% remained in the
      study for the full 3 years. One pregnancy occurred during the study which was
      considered by the investigator to be the result of misuse of the drug, giving an
      uncorrected Pearl Index of 0.07. Cycle control with the trial preparation was
      good, especially in women who did not miss any pills. By cycle 3, only 10.2% of
      women who had not missed pills reported intermenstrual bleeding (scanty or
      medium/excessive bleeding) and this decreased to 2.3% by cycle 36. The
      preparation was well tolerated, with a low incidence of unprompted adverse
      events. There were no clinically significant changes in mean body weight or blood
      pressure. Over the 3 years of the study, 10% of women withdrew from the study for
      reasons related mostly to mild adverse events. Results from this study
      demonstrate that the trial preparation is a reliable and well-tolerated oral
      contraceptive that provides good cycle control.

PMID- 8737191
TI  - Clinical evaluation of near-continuous oral micronized progesterone therapy in
      estrogenized postmenopausal women.
AB  - In an open non-comparative prospective trial of 12 months' duration, we
      investigated the role of a novel hormone replacement therapy regimen in 40 post
      menopausal women who sought hormone replacement therapy. The regimen consisted of
      continuous administration of 0.625 mg of conjugated equine estrogen coupled with
      a fixed low-dose of micronized oral progesterone administered for 23 days every
      calendar month. The regimen was well-tolerated, producing no major side-effects
      and was effective in relieving menopausal symptoms. The study showed that 40% of
      the women experienced side-effects and 20% withdrew from the study. Half of the
      20% of the women who dropped out did so for reasons not related to treatment. All
      symptomatic women experienced improvement after the 1st month, and virtually all
      were asymptomatic by the 3rd month of treatment, persisting until the end of the
      trial with the average number of hot flushes per day declining from the
      pretreatment levels by 96%. Amenorrhea was observed in 47% of patients,
      amenorrhea and minimal vaginal bleeding in 78% but acyclic bleeding was present
      in 28% of those in whom bleeding was re-established. Endometrial atrophy was
      induced in the majority of patients and no atypical endometrial hyperplasia was
      encountered. No significant changes were observed in blood glucose or liver
      enzymes. The mean percentage changes from baseline for serum cholesterol,
      triglycerides, high-density lipoprotein (HDL) cholesterol, low-density
      lipoproteins (LDL) and LDL/HDL ratio were -6%, +32% (p < 0.001), -16% (p < 0.05),
      +15% (p < 0.05) and -23% (p < 0.05), respectively. The regimen was clinically
      effective and its apparent lack of major side-effects, the protective effect on
      the endometrium, the added advantage of minimal vaginal bleeding and the
      beneficial effect on lipid/lipoprotein levels, offer an attractive therapy and
      improved compliance with postmenopausal hormone replacement therapy.

PMID- 8737192
TI  - Transdermal estrogen replacement therapy in normal perimenopausal women: effects
      on pituitary-ovarian function.
AB  - The effects of 6 months of hormone replacement therapy by transdermal estradiol
      patches (0.05 mg/day for 21 days) and oral progestogens (10 mg/day for 10 days)
      on hypothalamic-pituitary-ovarian function was evaluated in 32 perimenopausal
      women, aged 42-47 years, with irregular anovulatory cycles and menopausal
      symptoms. Hormone levels evaluated on the 8th and 24th day of the cycle preceding
      therapy showed follicle-stimulating hormone (FSH) levels above 15 mIU/ml,
      estradiol less than 45 pg/ml and progesterone less than 800 pg/ml. During
      therapy, there was an improvement in menopausal symptoms, a decrease in
      luteinizing hormone (LH) and FSH levels, an increase in estradiol levels and the
      transdermal patches were well tolerated. At the end of therapy, 19 women
      continued to have regular ovulatory cycles with progesterone levels similar to
      those in luteal phase. FSH and LH concentrations were significantly lower than
      before therapy. This study shows that hormone replacement therapy not only
      improves menopausal symptoms but may also restore the hypothalamic-pituitary
      ovarian function.

PMID- 8737193
TI  - The role of follicle-stimulating hormone in the selection of follicles in human
      ovaries: a survey of the literature and a proposed model.
AB  - A review of the literature resulted in a model consisting of three follicle
      stimulating hormone (FSH)-related mechanisms of follicle selection in the human
      ovarian cycle. The FSH-dependent selection of dominant follicles is the result of
      varying FSH serum levels on the one hand, and a varying follicular sensitivity to
      FSH on the other hand. The first FSH-related mechanism of follicle selection is
      the intercycle rise of FSH which induces the ongoing development of a reasonable
      number of follicles during the early follicular phase. The intercycle FSH level
      should surpass the FSH threshold of the follicles with the highest FSH
      sensitivity, but the FSH level should not be too high because many other less
      sensitive follicles might also be stimulated to develop. The second and third
      mechanisms act together during the mid- to late follicular phase. During the mid-
      and late follicular phases, the number of dominant follicles is reduced by the
      synergistic actions of a decreasing FSH level and the differentiation of the
      follicular sensitivity to FSH. Follicles destined to become dominant gain
      sensitivity to FSH, whereas follicles destined to become atretic lose their
      sensitivity to FSH. This differentiation of follicular sensitivity to FSH is the
      result of several endo-, para- and autocrine factors which modulate the effect of
      FSH on the growing follicle. The differentiation of follicular sensitivity to FSH
      supports the effect of the decreasing FSH level. Only the most sensitive follicle
      will become dominant. The other follicles will become atretic. The presented
      model may be of use not only for interpretation of the results of ovarian
      stimulation, but also to put the growing amount of data on growth factors and
      other substances which modulate the effects of FSH in the dynamic context of
      follicle selection.

PMID- 8737194
TI  - Measurement of health outcome and associated costs in cardiovascular disease.
AB  - As a result of scarcity of resources, combined with increased demand and the
      introduction of newer, more expensive technologies, choices have to be made about
      the allocation of funds between competing therapeutic options and priorities.
      Economic evaluation provides a means of making such choices more rational and the
      allocation of resources more efficient. Essentially, there are four types of
      health-economic evaluation: cost-minimization, cost-effectiveness, cost-utility
      and cost-benefit analysis. Costs associated with cardiovascular care amount to 12
      13% of the Swedish healthcare budget. Most of the direct costs associated with
      treating cardiovascular disease are spent on inpatient care. The indirect costs
      associated with morbidity and mortality are much greater than direct costs. The
      treatment of hypertension provides a good example of how direct costs of therapy
      must be balanced against long-term benefits. Long-term costs of uncontrolled
      hypertension include those resulting from other cardiovascular diseases for which
      hypertension is a significant risk factor, involving the brain, kidneys and
      arterial system. Benefits from anti-hypertensive therapy are greater in older
      patients and in those with more severe blood pressure elevation. In those over 70
      years old with a diastolic blood pressure between 100 and 104 mmHg, effective
      anti-hypertensive therapy has actually been demonstrated to result in a cost
      saving.

PMID- 8737195
TI  - Patient non-compliance with drug regimens: measurement, clinical correlates,
      economic impact.
AB  - Poor compliance with rationally prescribed drug regimens attenuates benefits of
      treatment, making compliance a key link between process and outcome in ambulatory
      care. Compliance is defined as "the extent of correspondence between the
      patient's actual dosing history and the prescribed regimen'. Electronic
      monitoring methods reveal that > 30% of patients omit many prescribed doses,
      irrespective of disease, prognosis, or symptoms. Some drugs are better able than
      others to maintain therapeutic action during the more common lapses in dosing.
      These are called "forgiving' drugs; their duration of action is more than twice
      the prescribed interval between doses, allowing action to continue when one or
      more doses are missed. Forgiveness has limits, so long lapses in dosing will
      nullify action of any drug, with economic consequences that depend on the
      clinical consequences of lapsed action, or, with some drugs, rebound effects.
      These practical points have only come to light with the use of electronic
      monitoring of compliance, which avoids the biases created by tablet counts and
      other methods that make it easy for patients to censor evidence for omitted
      doses. All else being equal, the most forgiving drug in its class will be
      associated with the best outcomes, for it will be least impacted by prevalent
      poor and partial compliance.

PMID- 8737196
TI  - Benefits of adherence to anti-hypertensive drug therapy.
AB  - Long-term adherence or compliance with anti-hypertensive drug therapy is poor. It
      has been estimated that within the first year of treatment 16-50% of
      hypertensives discontinue their anti-hypertensive medications. Even among those
      who remain on therapy long term, missed medication doses are common.
      Epidemiological studies have shown that drug-treated hypertensives have higher
      blood pressures than age-, gender- and body mass index-matched normotensives. In
      addition, drug-treated hypertensive men and women who achieve blood pressure
      normalization are less likely to die over a 9.5-year period than those whose
      blood pressure remains elevated while taking anti-hypertensive drugs. Thus, one
      reason for less than optimal reduction of blood pressure-related cardiovascular
      renal risk in drug-treated hypertensives is inadequate blood pressure lowering.
      Quantifiable excess risk has been documented even in the short term ( < 1 year)
      after interruption or discontinuation of anti-hypertensive medications as total
      healthcare costs are higher, mostly because of higher hospitalization rates. Data
      from the Treatment of Mild Hypertension Study (TOMHS) are relevant to long-term
      adherence to various anti-hypertensive drug monotherapies. At 48 months, 82.5%
      and 77.8% of participants remained on amlodipine and acebutolol, respectively
      (both P < 0.01 compared with placebo). However, only 67.5%, 66.1% and 68.1%,
      respectively, of chlorthalidone, doxazosin and enalapril participants remained on
      these drugs as monotherapy at 48 months. Differential adherence to long-term anti
      hypertensive drug therapy could translate into a greater risk of blood pressure
      related complications and higher overall healthcare expenditures. Strategies to
      minimize the deleterious impact of therapeutic non-adherence with anti
      hypertensive medications as well as the clinical and cost implications of the
      TOMHS data will be discussed.

PMID- 8737197
TI  - Therapeutic implications of drug "holidays'.
AB  - While a patient may appear to be fully compliant with respect to quantity of
      medication ingested, the timing of doses can vary considerably. This may
      introduce protracted intervals between doses, particularly if dosing frequency is
      greater than once daily. This commonly presents in the form of drug holidays,
      where dosing is omitted for 1 or more days, followed by a resumption of full
      strength dosing, possibly resulting in excessive drug effects when dosing
      suddenly resumes, rebound effects when dosing is suddenly stopped and a period
      without effective drug action. Poor compliance has not only been associated with
      poorer treatment outcome, but also with financial consequences. It has been
      suggested that hospitalization due to non-compliance accounts for 11.7% of all
      healthcare expenditure in the U.S.A. Differences between drugs, in terms of both
      their concentration-time profiles and their duration of action, will lead to some
      agents being more effective than others in the face of interruptions in dosage. A
      drug with an intrinsically long duration of action, such as the calcium
      antagonist amlodipine, will provide better therapeutic coverage than those with a
      shorter duration of action and therefore minimize effects generated by an
      intermittent pattern of dosing.

PMID- 8737198
TI  - Benefit and costs of anti-hypertensive treatment.
AB  - Hypertension is common throughout the world and represents the single greatest
      risk factor for increasing cardiovascular mortality, cardiovascular morbidity and
      overall mortality. Diseases associated with hypertension are not only, in
      general, of a chronic disabling nature, but, in most instances, require frequent
      hospitalization, with expensive drug treatment and management. Stroke, coronary
      heart disease, congestive heart failure and chronic renal insufficiency represent
      the most commonly encountered corollaries of inadequately treated hypertension.
      Anti-hypertensive treatment is accompanied by a reduction of hypertension-related
      cardiovascular risk and a clearcut benefit in terms of reduced incidence of major
      cardiovascular complications of hypertension and overall mortality. This benefit
      has frequently been underestimated in many clinical trials. Attempts to improve
      the cost-benefit ratio have included the use of treatment strategies based upon
      24-h control of blood pressure, since it has been demonstrated that hypertension
      related end-organ damage correlates more closely with 24-h average blood pressure
      and with 24-h blood pressure variability than with blood pressure measured in the
      clinic. It is hoped that new anti-hypertensive agents, which smoothly reduce 24-h
      blood pressure profile, will further reduce the incidence of hypertension-related
      end-organ damage.

PMID- 8737199
TI  - Can improved quality of care reduce the costs of managing angina pectoris?
AB  - Angina pectoris is a common symptom in patients over 50 years and is usually
      secondary to myocardial ischaemia resulting from coronary artery disease. The
      management of angina should be aimed at the maintenance or improvement of quality
      of life and delaying death. There are three strategies that may be adopted:
      medical, percutaneous transluminal coronary angioplasty and surgery. The majority
      of patients with angina can be controlled symptomatically most of the time by
      medical treatment alone. Any assessment of cost of treatment must take into
      account the cost of investigation, treatment, the morbidity associated with
      procedures or side effects of drugs, together with that of recurrent
      hospitalization, prolonged life and premature death. In addition, the duration of
      treatment has a major bearing on cost. Taking these factors into account, medical
      therapy is the least expensive short- and long-term treatment for angina
      pectoris. A medical approach to treatment also has considerable advantages over
      an interventional approach in terms of major morbidity. Only one of six surgical
      trials has demonstrated a survival benefit.

PMID- 8737200
TI  - More evidence for a beneficial effect of platelet glycoprotein IIb/IIIa-blockade
      during coronary interventions. Latest results from the EPILOG and CAPTURE trials.

PMID- 8737201
TI  - Temperature-controlled radiofrequency current ablation--what temperature?

PMID- 8737202
TI  - Cardio-oesophageal reflex and "linked angina'--is the way to a man's (or woman's)
      heart through the stomach?

PMID- 8737203
TI  - Spectral analysis of RR variability during transient myocardial ischaemia: have
      we moved from the computer console to the bedside?

PMID- 8737204
TI  - Non-invasive markers of coronary reperfusion in acute myocardial infarction.

PMID- 8737205
TI  - Angina, exercise and food.

PMID- 8737206
TI  - Primary PTCA for acute myocardial infarction--a logistic comment.

PMID- 8737207
TI  - The importance of reducing delay in acute myocardial infarction.

PMID- 8737208
TI  - The Sicilian gambit: an opening move that loses the game?

PMID- 8737209
TI  - Myocardial contrast echocardiography in acute myocardial infarction.
      Pathophysiological background and clinical applications.
AB  - Myocardial contrast echocardiography is a technique used in experimental and
      clinical settings in order to visualize the pattern of intramyocardial perfusion.
      In the acute phase of myocardial infarction, regional absence of flow during
      myocardial contrast echocardiography delineates the area at risk of necrosis,
      while the definitive non-perfused area expresses infarct size. Reopening the
      infarct-related artery, which may be achieved spontaneously by thrombolysis or
      percutaneous transluminal coronary angioplasty, is not a reliable indicator of
      intramyocardial reperfusion. If myocardial ischaemia due to coronary occlusion
      has been sufficiently prolonged and severe, not only myocyte viability, but also
      microvascular integrity is lost. Myocardial contrast echocardiography, using
      intracoronary injection of sonicated contrast medium, gives information about
      microvascular integrity and the effective presence of intramyocardial reflow.
      Anatomical integrity of microvasculature does not necessarily imply preserved
      function, and thus the microvessel vasodilating reserve may also be impaired.
      Myocardial contrast echocardiography has the potential to assess alterations in
      microvascular function, showing, in the myocardial area with reduced coronary
      reserve, a relatively reduced increase in echocontrast signal intensity when an
      intravenous vasodilator agent is administered.

PMID- 8737210
TI  - Heart rate variability. Standards of measurement, physiological interpretation,
      and clinical use. Task Force of the European Society of Cardiology and the North
      American Society of Pacing and Electrophysiology.

PMID- 8737211
TI  - Mortality, reinfarction, left ventricular ejection fraction and costs following
      reperfusion therapies for acute myocardial infarction.
AB  - The comparative efficacy of thrombolytic drugs and primary angioplasty for acute
      myocardial infarction have recently been studied, but long-term follow-up data
      have not yet been reported. We conducted a randomized trial involving 301
      patients with acute myocardial infarction; 152 patients were randomized to
      primary angioplasty and 149 to intravenous streptokinase. Left ventricular
      function was assessed with a radionuclide technique both at hospital discharge
      and at the end of the follow-up period. Follow-up data were collected after a
      mean (+/-SD) of 31 +/- 9 months. Total medical costs were calculated. At the end
      of the follow-up period, 5% of the angioplasty patients had died from a cardiac
      cause compared to 11% of the patients randomized to intravenous streptokinase, P
      = 0.031. Cardiac death or a non-fatal reinfarction occurred in 7% of angioplasty
      patients compared to 28% of streptokinase patients, P < 0.001. There was a
      sustained benefit of angioplasty compared to streptokinase on left ventricular
      function. The total medical costs in the two groups were similar. Coronary
      anatomy (patency and single or multivessel disease), infarct location and
      previous myocardial infarction were important determinants of clinical outcome
      and costs. After 31 +/- 9 months of follow-up, primary angioplasty compared to
      intravenous streptokinase results in a lower rate of cardiac death and
      reinfarction, a better left ventricular ejection fraction, and no increase in
      total medical costs.

PMID- 8737212
TI  - Spectral analysis of heart rate variability before and during episodes of
      nocturnal ischaemia in patients with extensive coronary artery disease.
AB  - Spectral analysis of heart rate variability was used to assess autonomic nervous
      system activity associated with episodes of nocturnal myocardial ischaemia in 32
      patients (20 men, age 58 +/- 9 years) with extensive coronary artery disease.
      Twenty-four hour Holter tape recordings were analysed and spectral indexes of
      heart rate variability were computed by fast Fourier analysis on 2 min segments
      covering the period from 10 min before to 10 min after each nocturnal ischaemic
      episode, defined as ST segment depression > or = 1 mm lasting at least 4 min.
      Spectral power was measured at low frequencies (LF: 0.06-0.10 Hz) and high
      frequencies (HF: 0.15-0.40 Hz) and the ratio LF/HF was calculated. RESULTS. A
      total of 30 episodes of nocturnal ischaemia were analysed. High frequency
      spectral power showed a clear decrease during the 10 min before the onset of
      ischaemia, remained steady until the end of the episode, and returned to normal
      by 6 min after. Low frequency spectral power fluctuated throughout the ischaemic
      episodes with no clear pattern of variation. The low/high frequency ratio
      reflected mainly the changes in high frequency. CONCLUSIONS. Sympathetic
      predominance due to para-sympathetic withdrawal is the principal change in
      autonomic nervous system activity associated with episodes of nocturnal
      ischaemia.

PMID- 8737213
TI  - The effect of meals of differing composition on exercise tolerance in patients
      with angina pectoris.
AB  - In this study we compared different dietary constituents and their effect on the
      angina threshold. We compared carbohydrate-rich, fat-rich and balanced liquid
      diets on effort tolerance in 14 patients of mean (range) 61 (41-73) years of age
      with chronic stable angina. On four different occasions at least 1 week apart,
      patients had exercise treadmill tests after an overnight fast and then after a
      rest period of 1 h ingested one of three different approximately isocalorific
      (about 4000 kJ) liquid drinks of 600 ml consisting mainly of: fat, carbohydrate
      or a balanced meal with an equal volume of water as control. Meals were given in
      random order. Analysis of the mean (SD) differences in heart rate between fasting
      and the post-prandial state for the different meals revealed a significant
      increase between water and the other meals, fat (+4(6) beats.min-1 P < 0.002),
      balanced (+9(17) beats.min-1 P < 0.004), and carbohydrate (+10(12) beats.min-1 P
      < 0.0002). There was no significant difference between the groups as regards
      systolic or diastolic blood pressure. Cardiac output increased following the
      meals but decreased after water; however, there was a significant difference
      between water and balanced meals. Exercise tolerance fell following all the meals
      but was significantly greater after a balanced (mean (SD) -108(129) s P < 0.01)
      and carbohydrate meal (-92(52) s P < 0.001). The reduction in exercise duration
      following a fat meal (-36(53)s) was not significantly different from that
      following water (-8(43) s) but was significantly smaller than after a
      carbohydrate meal (P < 0.02). Time to 1 mm of ST depression showed similar
      changes to that of total exercise duration, being significantly lower after a
      carbohydrate (mean (SD) -76(77) s P < 0.01) and balanced meal (-76(63) s P <
      0.005). Time to 1 mm ST depression, although reduced by a fat meal (-15(84) s)
      was significantly less than after a carbohydrate meal (P < 0.02). In conclusion,
      patients with chronic stable angina have impaired effort tolerance and a lower
      angina threshold after high calorie containing liquid meals. Meals rich in
      carbohydrate have greater effects than meals where the majority of calories are
      derived from fat. Patients should be advised to avoid exercise in the first 30
      min after eating.

PMID- 8737214
TI  - Serum myoglobin for the early non-invasive detection of coronary reperfusion in
      patients with acute myocardial infarction.
AB  - The ideal non-invasive method for detecting coronary reperfusion has not yet been
      established. In 63 patients with acute myocardial infarction, serum myoglobin and
      creatine kinase-MB were measured every 15 min. Thrombolytic treatment was given
      (n = 52) and acute coronary angiography showed a patent infarct-related artery in
      49 patients while 14 patients had no coronary reperfusion. Median time to peak
      serum myoglobin was shorter (reperfusion group 178 min vs no reperfusion group
      480 min, P < 0.0001) than time to peak serum creatine kinase-MB (reperfusion
      group 550 min vs no reperfusion group 1080 min, P < 0.0001), P < 0.0001.
      Myoglobin appearance rate, calculated as the concentration at 2 h divided by
      baseline values (Mb2/Mb0) was highest in the reperfusion group (4.0 vs 1.6), P <
      0.001. An earlier proposed index, Mb2/Mb0 > 2.4 for identification of reperfusion
      2 h after thrombolytic therapy, showed predictive values of positive and negative
      tests of 0.94 and 0.44, respectively. Combining this index with signs of medium
      to larger infarct size (Mb2 > 200 micrograms.l-1) increased the predictive value
      of the negative test to 1.00. In patients with signs of minor infarcts (Mb2 < 200
      micrograms.l-1) the predictive values of positive and negative tests were 0.94
      and 0.79, respectively, 5 h after onset of thrombolytic therapy. An early rise
      and a peak in serum myoglobin values seems to be a reliable and simple non
      invasive indicator of successful and unsuccessful reperfusion therapy.

PMID- 8737215
TI  - Cardio-oesophageal reflex in humans as a mechanism for "linked angina'.
AB  - The aim of this study was to investigate the hypothesis that oesophageal acid
      stimulation reduces coronary blood flow in humans as a result of the presence of
      a cardio-oesophageal reflex which may provide a mechanism for "linked angina'. We
      studied the effect of oesophageal acid stimulation on coronary blood flow in 35
      syndrome X patients and 24 heart transplant patients. A fine tube was positioned
      into the patient's distal oesophagus. An intracoronary Doppler catheter was
      positioned in the proximal left anterior descending coronary artery for coronary
      blood flow measurements. Oesophageal instillation of 0.1 M hydrochloric acid was
      performed (60 ml over 5 min) and the measurements were repeated. The coronary
      blood flow was significantly reduced by acid oesophageal stimulation in the
      syndrome X group [pre-acid 78.9 +/- 36.4 ml. min-1, post-acid 50.8 +/- 32.9
      ml.min-1 (P = 0.0001)]. However, coronary blood flow in the heart transplant
      group, in whom the heart is denervated, was unaffected by acid infusion. We
      conclude that oesophageal acid stimulation can produce angina and significantly
      reduce coronary blood flow in humans. The lack of any significant effect in the
      heart transplant group, in whom the heart is denervated, suggests a neural
      reflex.

PMID- 8737216
TI  - Anti-ischaemic efficacy of L-propionylcarnitine--a promising novel metabolic
      approach to ischaemia?
AB  - L-propionylcarnitine, a naturally occurring derivative of L-carnitine, essential
      for mitochondrial fatty acid transport and high-energy phosphate exchange,
      acutely reduces myocardial ischaemia and improves ischaemia-induced cardiac
      dysfunction following intravenous administration. This randomized, crossover
      study was designed to compare the long-term anti-ischaemic effects of oral L
      propionylcarnitine with diltiazem in patients with stable, exercise-induced
      angina. After a 2-week washout phase of anti-anginal medication and a 2-week
      single-blind placebo period, 46 patients were included in the study, 23 of whom
      received 1500 mg L-propionylcarnitine daily for 6 weeks, and 23 diltiazem (180 mg
      daily for 3 weeks, followed by 360 mg daily for 3 weeks), crossing over to the
      other treatment after a 1-week washout period. Three patients on L
      propionylcarnitine and two on diltiazem discontinued. Both treatments resulted in
      comparable exercise duration (582 +/- 35 s and 588 +/- 33 s, mean +/- SEM), time
      to 0.1 mV ST depression (436 +/- 38 s and 465 +/- 36 s), and increase in time to
      0.1 mV ST depression from baseline (20% and 28%), L-propionylcarnitine and
      diltiazem, respectively. Diltiazem decreased the rate-pressure product at rest
      and exercise, L-propionylcarnitine did not. Both compounds significantly reduced
      ST depression at maximal exercise [23% (L-propionylcarnitine) vs 35% (diltiazem),
      P < 0.05 diltiazem vs L-propionylcarnitine]. Diltiazem increased the time to
      onset of angina by 22%. In contrast, no significant changes occurred with L
      propionylcarnitine. During the study, anginal attacks were reduced by 70% and
      57%, and nitroglycerin consumption decreased by 57% and 70%, L-propionylcarnitine
      and diltiazem, respectively. Thus, both L-propionylcarnitine and (high-dose)
      diltiazem result in anti-ischaemic effects and decrease anginal attacks in daily
      life. Although the effect of diltiazem on exercise-induced ischaemia appears more
      pronounced than that of L-propionylcarnitine, this novel metabolic approach to
      ischaemia warrants further development.

PMID- 8737217
TI  - Thrombolytic therapy reduces the incidence of left ventricular thrombus after
      anterior myocardial infarction. Relationship to vessel patency and infarct size.
AB  - BACKGROUND: Controversial evidence exists as to whether thrombolytic therapy
      reduces the incidence of left ventricular thrombus in acute myocardial infarction
      and, if so, how this relates to successful reperfusion. METHODS: Four hundred and
      eighteen consecutive patients underwent echocardiography and coronary angiography
      within 3 weeks of an acute myocardial infarction. A dyssynergic score was
      calculated by analysing regional wall motion in 18 left ventricular segments. The
      infarct-related artery was considered patent if TIMI grade 2 or 3 flow and less
      than 90% stenosis were present. Retrograde perfusion by Rentrop's grade 2 or 3
      collaterals was considered significant. RESULTS: Large anterior myocardial
      infarctions were associated with the highest prevalence (39%) of left ventricular
      thrombosis. Thrombus was also very frequent if the left anterior descending
      coronary artery was occluded and no collaterals to the infarct area were seen
      (75%). Anticoagulant therapy reduced the prevalence of left ventricular thrombus,
      regardless of whether the infarct-related vessel was patent or not. Conversely,
      in patients undergoing thrombolysis the incidence of left ventricular thrombosis
      was lower when the left anterior descending coronary artery was patent, and
      especially when an early creatine kinase peak, suggestive of reperfusion, was
      recorded (7%). Finally, the presence of left ventricular thrombosis was inversely
      related to the asynergy score. CONCLUSION: These observations suggest that the
      presence of left ventricular thrombus is related to the extent of myocardial
      damage. Thrombolytic therapy reduces thrombus probably by salvaging myocardium at
      risk.

PMID- 8737218
TI  - Determinants of delay between symptoms and hospital admission in 5978 patients
      with acute myocardial infarction. The TRACE Study Group. Trandolapril Cardiac
      Evaluation.
AB  - The aim of this study was to analyse the influence of patient characteristics on
      delay between onset of symptoms and hospital admission (patient delay) in acute
      myocardial infarction, and especially to assess the impact of risk factors for
      acute myocardial infarction on patient delay. A group of 6676 consecutive
      patients with enzyme-confirmed acute myocardial infarction, admitted alive to 27
      Danish hospitals over a 26 month period from 1990 to 1992, were studied. Due to
      missing information on delay or in-hospital acute myocardial infarction 698
      patients were excluded, leaving 5978 patients for analysis. Mean patient delay
      was 9.1 h, median delay 3.25 h (5 to 95 percentiles: 0.67-40.0 h). Thirty-four
      percent were admitted within the first 2 h, 68% within 6 h and 81% within 12 h of
      onset of symptoms. In multivariate logistic regression analysis, a greater than 2
      h patient delay was independently associated with male gender (odds ratio (OR) =
      0.809, P = 0.003), increased age (P = 0.0001), diabetes mellitus (OR = 1.269, P =
      0.03), left ventricular systolic function (wall motion index) (P = 0.02), onset
      from midnight to 0600h (OR = 1.434, P = 0.0001), onset on a weekday (OR = 0.862,
      P = 0.04), history of angina pectoris (OR = 1.198, P = 0.02), chest pain as
      initial symptom (OR = 1.293, P = 0.02), ventricular fibrillation (OR = 0.562, P =
      0.0001), ventricular tachycardia (OR = 0.620, P = 0.0001), Killip class > or = 3
      (OR = 0.709 P = 0.002), presence of ST elevation (OR = 0.810, P = 0.01) and ST
      depressions (OR = 0.847, P = 0.01). All these variables, except history of
      diabetes mellitus, angina pectoris, and chest pain as an initial symptom were
      also associated with a delay of more than 6 h. Thrombolytic therapy was
      administered to 55.8% of patients admitted within 2 h of an acute myocardial
      infarction, 48.5% of patients admitted within 2-6 h, 31.5% of patients admitted
      after 6-12 h and 11.9% of patients arriving later than 12 h after start of
      symptoms. CONCLUSION. Patient delay continues to be disappointingly long. This
      also applies for patients at a high risk of acute myocardial infarction (notably
      those with a history of diabetes mellitus and angina pectoris).

PMID- 8737219
TI  - First clinical experience with a new flexible low profile metallic stent and
      delivery system.
AB  - We report the first clinical use of a new, flexible, low profile, balloon
      expandable metallic stent and delivery system (ACS Multi-Link). The stent,
      designed in an effort to overcome the shortcoming of existing stents, has a low
      metal mass, superior scaffolding properties and favourable rheological
      characteristics. It also allows side branch access and is delivered via an
      innovative stent catheter. Ten stents were used to treat 10 patients with
      threatened abrupt closure after balloon angioplasty. All were successfully
      deployed, with a satisfactory angiographic result in nine. The patient with an
      unsatisfactory angiographic result proceeded to uneventful coronary bypass
      surgery. There were no other procedural or in-hospital complications. One patient
      developed restenosis and one had an intra-cerebral bleed following a fall. This
      new stent thus appears safe and effective when used to treat threatened abrupt
      closure. Due to its favourable characteristics, it may be well suited for
      reduction of restenosis. A multi-centre European registry (WEST) for primary
      implantation in 100 consecutive patients has now been completed.

PMID- 8737220
TI  - Temperature-controlled radiofrequency catheter ablation of manifest accessory
      pathways.
AB  - OBJECTIVES: The primary objectives of this study were to assess the feasibility
      of temperature-controlled radiofrequency catheter ablation of left and right
      sided manifest accessory pathways in patients with Wolff-Parkinson-White syndrome
      and to gain more insights into biophysical aspects of temperature-controlled
      catheter ablation in humans. BACKGROUND: The electrode-tissue interface
      temperature and other biophysical parameters are among important variables
      determining the efficacy and safety of radiofrequency ablation of accessory
      pathways. Experimental studies have shown that radiofrequency-induced tissue
      necrosis can be accurately predicted by monitoring of catheter tip temperature.
      METHODS: 38 consecutive patients (14 f, 24 m; aged 42 +/- 12 years) with
      anterograde conducting accessory pathways (left sided: n = 22; right sided: n =
      16) underwent temperature-controlled radiofrequency ablation (HAT 200S, Dr
      Osypka, Germany). The electrode temperature was monitored via a thermistor
      embedded into a 4 mm catheter tip. Power output was adjusted automatically during
      energy delivery in a closed loop system (preselected temp.: 70.1 +/- 5.8 degrees
      C). RESULTS: Accessory pathway conduction was successfully abolished in all
      patients after the delivery of 2.3 +/- 2.1 radiofrequency pulses (range: 1-9,
      median: 2). Interruption of the accessory pathway as evidenced by loss of
      preexcitation occurred after 5.9 +/- 5.4 s. At the time of the interruption of
      the accessory pathway the catheter tip temperature measured 54.2 +/- 11.2 degrees
      C in patients with left and 44.9 +/- 5.0 degrees C in patients with right sided
      accessory pathways, respectively (P < 0.008). Higher temperature levels during
      left sided applications did not shorten the time it took for the effect to appear
      (left sided accessory pathway: 7.5 +/- 6.3 s, right sided accessory pathway: 3.7
      +/- 2.9 s; ns). The catheter tip temperature was significantly higher during left
      compared to right sided applications after 5 (52.1 +/- 3.1 degrees C vs 47.2 +/-
      4.3 degrees C) and 10 s (61.5 +/- 6.2 degrees C vs 52.7 +/- 4.2 degrees C)
      following initiation of the impulse (P < 0.005). Power output and delivered
      energy did not differ significantly at the time of accessory pathway abolition.
      Peak values of delivered power (45.1 +/- 10.9 W vs 41.3 +/- 10.6 W; P < 0.05) and
      total delivered energy (2452 +/- 1335 J vs 1392 +/- 762 J; P < 0.02) were
      significantly higher in the group of right sided pathways compared to left sided
      applications. The peak temperature measured 77.1 +/- 13 degrees C during
      effective and 69.9 +/- 14 degrees C during ineffective energy applications (P <
      0.05). The time it took for the effect to appear was significantly longer in
      transiently effective pulses (10.4 +/- 7.2 s) compared to permanently effective
      applications (5.9 +/- 5.4 s; P < 0.02). Despite temperature control, an abrupt
      rise in impedance was observed in 10 of 89 (11%) energy applications. No
      procedure-related complications occurred. CONCLUSIONS: Temperature-controlled
      radiofrequency ablation of manifest accessory pathways is highly effective and
      safe. The temperature response is faster and significantly higher in left-sided
      energy applications compared to right-sided pulses. Peak temperature levels
      measured at the electrode tip are significantly higher during effective than
      ineffective pulses. Sudden rises in impedance are not completely prevented during
      temperature-controlled radiofrequency ablation of accessory pathway, although no
      procedure-related complications were noted in this patient cohort.

PMID- 8737221
TI  - Effects of respiration on left ventricular diastolic function in healthy
      children.
AB  - Pulsed Doppler echocardiographic indices of mitral valve filling were measured in
      20 healthy children, between 3 and 12.5 years old, in order to evaluate the
      effects of spontaneous respiration on left ventricular diastolic filling
      patterns. There were significant respiratory variations in four parameters of
      left ventricular diastolic function: The peak early filling velocity, the ratio
      of early to late peak filling velocity, and the ratio of early to late diastolic
      velocity-time integral decreased significantly during inspiration (mean decrease
      7%, P < 0.05; 16%, P < 0.01; and 12%, P < 0.05, respectively). On the other hand
      there was a significant increase in late peak filling velocity with inspiration
      (10% increase, P < 0.05). Other variables of left ventricular diastolic filling
      were unchanged with inspiration. These results suggest that assessment of left
      ventricular diastolic function in children should be standardized with regard to
      respiratory phases in any clinical application.

PMID- 8737222
TI  - The effects of isometric stress on left ventricular filling in athletes with
      isometric or isotonic training compared to hypertensive and normal controls.
AB  - Hypertrophy of the left ventricle may be associated with altered left ventricular
      filling dynamics. To test whether isometric and isotonic training affect left
      ventricular filling differently at rest and during isometric stress, 38 males, 13
      long distance runners, eight weight-lifters, eight hypertensive patients and nine
      age-matched healthy male controls with a mean age of 30 +/- 7 years, were studied
      before and after 90 s of 50% maximal handgrip force. Left ventricular Doppler
      filling parameters were compared in the four groups while they were resting and
      during isometric stress testing, and the results assessed in relation to left
      ventricular mass index and wall stress. All subjects had normal resting filling
      patterns except for hypertensive patients, and peak meridional wall stress was
      low in both athletic groups at rest. Weight-lifters had a hypertensive response
      during isometric stress testing, associated with a reduction in peak E velocity
      and a marked increase in peak A velocity, resembling the filling pattern in
      hypertensive subjects. In runners the filling pattern remained normal. Thus,
      while the resting left ventricular pattern was normal in all athletes, isometric
      stress testing was associated with a hypertensive filling pattern only in weight
      lifters compared to normal filling in runners.

PMID- 8737223
TI  - Determinants of heart rate variability in heart transplanted subjects during
      physical exercise.
AB  - Respiratory sinus arrhythmia has been described in heart transplanted subjects.
      In order to investigate the mechanisms involved in the generation of this
      condition in the transplanted heart and its evolution after surgery, graded
      exercise was performed (0-75 W in 25 W steps) on a cycle ergometer by 41 subjects
      (mean age 44 years) who had undergone heart transplantation 28 months (range 3
      60) earlier and by six age matched-control subjects. R-R interval, respiratory
      signal, O2 consumption (VO2) and CO2 production (VCO2) were measured. Respiratory
      sinus arrhythmia was assessed by the autoregressive power spectrum of the R-R
      interval and respiration. All subjects reached the anaerobic threshold (heart
      transplants: 60% at 50 W, 40% at 75 W Controls: 150 W). In control subjects, the
      respiratory sinus arrhythmia was higher than in heart transplanted subjects (5.80
      +/- 0.30 vs 1.45 +/- 0.16 1n ms2) and it decreased significantly (4.66 +/- 0.30
      1n ms2, P < 0.05) during exercise, despite the increase in breathing rate and
      depth. When, the group of heart transplanted subjects was considered as a whole,
      respiratory sinus arrhythmia was found to be present in all conditions. It
      significantly increased at 25 W (from 1.45 +/- 0.16 to 2.00 +/- 0.17 1n ms2, P <
      0.01), then significantly fell below baseline during recovery (to 0.97 +/- 0.23
      1n ms2, P < 0.01). Multiple regression analysis showed that a linear combination
      of heart rate (inverse correlation) and VO2 (direct correlation) together with
      months having passed since transplantation surgery, could explain the observed
      changes in heart rate during exercise (multiple regression: r = 0.658, P <
      0.0001). In five long-term transplanted subjects, non respiratory-related low
      frequency (0.1 Hz) waves were present on the R-R spectrum, but respiratory sinus
      arrhythmia is also present in the recently transplanted heart and depends on the
      opposing effects of ventilation and heart rate. In a few cases, sympathetic
      modulation (re-innervation) could not be excluded.

PMID- 8737224
TI  - Cyclic variation in myocardial gray level as a marker of viability in man. A
      videodensitometric study.
AB  - Experimental and human studies have shown that a preserved cyclic (diastolic-to
      systolic) echoreflectivity variation, assessed by radiofrequency sampling of
      backscatter signal with non-commercially available prototypes, identifies
      viability in a myocardial segment with a resting dyssynergy. The objective of
      this study was to assess whether a videodensitometric analysis of myocardial gray
      level variation during cardiac cycle might identify viable but dyssynergic
      myocardium in a clinical setting. Thirty-four patients with a resting dyssynergy
      (akinesis in 26, marked hypokinesis in eight) in the septum and/or inferno
      posterior wall were evaluated by videodensitometry. All echo studies were
      performed with commercially available instruments in the long axis parasternal
      view, with quantitative analysis of gray levels performed off-line on digitized
      images. Segmental wall motion was assessed with a 16 segment model of the left
      ventricle, each scored from 1, normal, to 4, dyskinetic. A follow-up echo study
      was obtained in all patients > 4 weeks after successful revascularization (in 22
      by angioplasty, in 12 by bypass surgery). Two groups of segments were identified:
      18 viable segments (contractile improvement of 1 grade or more in resting
      function after revascularization); 16 necrotic segments (no contractile
      improvement in resting function after revascularization). The % cyclic variation
      was higher in viable vs necrotic segments (26 +/- 16 vs 1 +/- 13%, P < 0.01), in
      spite of similar % systolic thickening (5 +/- 5 vs 4 +/- 6%, P = ns) and end
      diastolic thickness (10 +/- 2 vs 10 +/- 2 mm, P = ns). When individual patient
      analysis was performed, % cyclic variation was below the 95% confidence limits
      obtained from normal control regions (n = 34; % cyclic variation = 38 +/- 14) in
      two out of 18 viable and in 14 out of 16 necrotic segments. A cut-off of > or =
      9.4% cyclic variations in a dyssynergic segment yielded 89% sensitivity and 88%
      specificity for predicting functional recovery following successful
      revascularization. In conclusion, viable dyssynergic myocardial segments show a
      cyclic gray level variation at rest, which can be detected by simple
      videodensitometric analysis, much less technologically demanding than
      radiofrequency backscatter evaluation.

PMID- 8737225
TI  - Prediction of reversibility of wall motion abnormalities after revascularization
      using F18-fluorodeoxyglucose single photon emission computed tomography.

PMID- 8737226
TI  - Haemorrhagic retinopathy in patients admitted with acute cardiac chest pain.

PMID- 8737227
TI  - Preliminary results of a nutritional survey in a sample of 35,000 Italian
      schoolchildren.
AB  - An investigation of the nutrient intake of a large-scale sample (n = 35,072),
      drawn from the Italian school-age population (7-10 years) was carried out in a
      nationwide survey of nutritional patterns. Friuli, the Piedmont, Latium and
      Sicily regions were selected as representative of the nation's north-south and
      east-west socio-economic divisions. A food frequency questionnaire was used to
      assess nutritional intake. Traditional methods of 24-h dietary recall and a
      weighted food diary were used in subsamples to assess the validity of the food
      frequency questionnaire. Our data suggest that the average diet of Italian
      schoolchildren is rich in protein (especially animal proteins) and lipids
      (prevalently saturated fatty acids), but that carbohydrate and fibre intakes
      remain generally low. The relatively low calcium intake among girls and a
      widespread, more than adequate iron intake are also noteworthy. The food and
      nutrient intakes assessed suggest a dietary pattern with several positive points,
      but also reveal potential hazards for a wider population spectrum. The type of
      large-scale nutritional monitoring with a multi-method approach can be used in
      Italy and elsewhere to describe the dietary trends of a school-age population.

PMID- 8737228
TI  - Enhanced effect of clarithromycin on neutrophil function in vitro.
AB  - An in vitro study was carried out to investigate the effect of clarithromycin, a
      new oral macrolide, on neutrophil reactive oxygen species generation and
      chemotaxis. It was found that neutrophil-generated O2-, H2O2 and OH. levels were
      significantly increased by clarithromycin at concentrations of 50 micrograms/ml
      (P < 0.05). The drug also significantly increased chemotaxis (P < 0.05). These
      results indicate that clarithromycin may enhance the activation of neutrophils in
      vivo.

PMID- 8737229
TI  - Effects of recombinant human erythropoietin in infants with very low birth
      weights.
AB  - Anaemia of prematurity, a postnatal fall in haemoglobin concentration and
      haematocrit, is particularly common in those born at less than 32 weeks of
      gestation. Experimental and clinical data implicate inadequate erythropoietin
      production as an important reason. In this study recombinant human erythropoietin
      (r-HuEpo) was used in an attempt to treat or prevent this anaemia and thereby
      provide an alternative to erythrocyte transfusions. Premature infants (birth
      weight < or = 1250 g and gestational age < or = 32 weeks), who were likely to
      need transfusions, were randomly assigned to receive 4 weeks of treatment with
      either subcutaneously administered r-HuEpo (200 U; n = 12) or placebo (n = 12),
      three times weekly. All patients had oral supplements of elemental iron at a dose
      of 3 mg/kg/day. Treatment was started in the third week of life. Reticulocyte
      counts were significantly raised (P < 0.05) in the group treated with r-HuEpo at
      the end of treatment. The neonates in the group treated with r-HuEpo needed fewer
      erythrocyte transfusions than those in the placebo group during treatment. There
      were no toxic effects attributable to r-HuEpo. The results indicate that
      treatment of infants with very low birth weights with r-HuEpo will reduce their
      need for erythrocyte transfusions.

PMID- 8737230
TI  - Significance of increased accumulation of type VI collagen and transforming
      growth factor beta 1 in tubulointerstitial damage in hypertensive
      nephrosclerosis: an immunohistochemical study.
AB  - The distribution of type VI collagen and transforming growth factor beta 1 (TGF
      beta 1) was studied by immunohistochemistry in 12 renal biopsy specimens of
      hypertensive nephrosclerosis and five control cases. In control kidneys, the
      immunostaining of type VI collagen was found in the mesangium, glomerular
      basement membrane and tubular basement membrane. For TGF beta 1, mesangium,
      glomerular basement membrane, tubular basement membrane and tubular epithelial
      cells stained positively in the control kidneys. In contrast to the control
      cases, markedly increased immunostaining for both type VI collagen and TGF beta 1
      was consistently observed in tubulointerstitial damage in hypertensive
      nephrosclerosis. These immunohistochemical findings provide the evidence for a
      parallel increase of both type VI collagen and TGF beta 1 during the process of
      tubulointerstitial injury in hypertensive nephrosclerosis. From the results of
      the present study, it is speculated that TGF beta 1 may contribute to the
      tubulointerstitial injury by stimulating increased synthesis of various
      extracellular matrix including type VI collagen.

PMID- 8737231
TI  - Cardiorespiratory function as assessed by exercise testing in patients with non
      insulin-dependent diabetes mellitus.
AB  - Exercise testing was used to examine 19 cardiorespiratory diabetes mellitus
      patients, aged 32-68 years (body mass index, 27.8 +/- 4.8 kg/m2), and 16 healthy
      volunteers, aged 23-57 years (body mass index, 22.7 +/- kg/m2). A graded cycling
      exercise test was done, monitoring gas exchange, ventilation and heart rate.
      Values were significantly higher in the non-insulin-dependent diabetes mellitus
      (NIDDM) patients than in the controls for fasting blood glucose (P < 0.01),
      glycosylated haemoglobin (P < 0.01), body weight (P < 0.05) and body mass index
      (P < 0.05). The exercise testing produced values that were significantly lower in
      the patients with NIDDM than in the controls for percentage oxygen uptake (P <
      0.05), maximum load (P < 0.05), maximum metabolic equivalent (P < 0.01) and
      maximum oxygen uptake per unit body weight (P < 0.01). Ventilatory capacity and
      forced expiratory volume at 1 sec did not differ significantly in the two groups.
      These results suggest that general fitness is diminished due to reduced
      cardiorespiratory function in patients with NIDDM.

PMID- 8737232
TI  - Factors related to the development and progression of diabetic retinopathy in
      patients with type 2 diabetes.
AB  - This study was intended to clarify the factors associated with the development
      and progression of diabetic retinopathy in patients with Type 2 diabetes. A total
      of 107 patients with Type 2 diabetes underwent fundoscopic examination by an
      ophthalmologist, and the factors that might be associated with the severity of
      retinopathy were investigated. Analysis of variance and the chi 2 test were
      performed to determine whether 22 separate factors were associated with the
      severity of diabetic retinopathy. There were significant associations between
      retinopathy and duration of disease, systolic blood pressure, urinary albumin
      index, and blood urea nitrogen. Multiple regression analysis with retinopathy as
      the criterion variable and 20 other factors as explanatory variables revealed
      that, of those explanatory variables showing statistical significance, the
      strongest associations were with duration of disease and type of diabetic
      therapy, in that order. The chi 2 test also revealed significant associations
      between retinopathy and both the type of diabetic therapy and the use of anti
      hypertensive therapy. The results suggest that the duration of illness and the
      type of diabetic therapy are strongly related to the development and progression
      of retinopathy in patients with Type 2 diabetes. These findings suggest that
      insulin deficiency in patients with Type 2 diabetes should be corrected as early
      and as vigorously as possible, and that modification of daily activities to
      achieve a more nearly non-diabetic state should be instituted first, with
      supplementary drug therapy added as required.

PMID- 8737233
TI  - Pituitary macroadenoma in Addison's disease.
AB  - Long-standing primary failure of pituitary-dependent endocrine glands may lead to
      hyperplasia of the pituitary cells. These changes in the pituitary gland may be
      correlated with the severity and duration of target-endocrine gland
      insufficiency. Production of adrenocorticotrophic hormone by the pituitary tumour
      and modest hyperprolactinaemia may develop due to adrenocortical insufficiency,
      but production of prolactin by the pituitary tumour due to primary adrenal
      insufficiency is rare. A case study is presented, with primary adrenal
      insufficiency associated with hyperprolactinaemia and pituitary macroadenoma
      (most probably prolactinoma). Plasma levels of prolactin were found to decrease
      after glucocorticoid, mineralocorticoid and bromocriptine therapy.

PMID- 8737234
TI  - Dr. Sen-itiroh Hakomori.

PMID- 8737235
TI  - A reflection on the early history of glycosphingolipids.

PMID- 8737236
TI  - Characterization of gangliosides from Ehrlich ascites tumour cells and their
      variants.
AB  - Differences in the nature of the gangliosides present in two types of Ehrlich
      ascites tumour (EAT) cells, the adherent and non-adherent EAT cells, were
      studied. Gangliosides were isolated by DEAE Sephadex column chromatography and
      analysed by high-performance thin-layer chromatography (HPTLC). The non-adherent
      EAT (na-EAT) cells which grow in the peritoneal cavity of mice were selected for
      growth on basement membrane and tissue culture plastic to give the adherent EAT
      (a-EAT) cells. na-EAT cells contained 1.57 nmol lipid-bound sialic acid per mg
      protein and at least 12 different gangliosides, including major gangliosides such
      as GM3, GM2, GM1, GD3, GD1a and GT1b. On the other hand, the ganglioside pattern
      of a-EAT cells differed significantly from that of na-EAT cells, both
      quantitatively and qualitatively. The content of lipid-bound sialic acid in a-EAT
      cells was only 0.24 nmol per mg of protein. The gangliosides in a-EAT cells were
      characterized as GD1a and trisialogangliosides and, significantly, a-EAT cells
      did not contain monosialogangliosides. Neutral glycolipids were isolated from
      both cell lines and their patterns were compared. In contrast to the gangliosides
      pattern, their neutral glycolipid patterns were similar. Glucosylceramide and
      lactosylceramide were the major components in both types of cells. In addition to
      na- and a-EAT cells, a-EAT cells were passaged in mice by intraperitoneal
      injection, giving rise to a third variant (c/m EAT cells). We analysed the
      gangliosides in c/m EAT cells to determine whether there was a change in the
      ganglioside pattern found in na-EAT cells. After repeated passage of c/m EAT
      cells in mice, the pattern of gangliosides shifted to that of na-EAT cells.
      Alterations of ganglioside composition may be associated with the growth
      environment of the murine peritoneal cavity; alternatively, a selection process
      may have occurred.

PMID- 8737237
TI  - Expression and localization of Lewis(x) glycolipids and GD1a ganglioside in human
      glioma cells.
AB  - We analysed the glycolipid composition of glioma cells (N-370 FG cells), which
      are derived from a culture of transformed human fetal glial cells. The neutral
      and acidic glycolipid fractions were isolated by column chromatography on DEAE
      Sephadex and analysed by high-performance thin-layer chromatography (HPTLC). The
      neutral glycolipid fraction contained 1.6 micrograms of lipid-bound
      glucose/galactose per mg protein and consisted of GlcCer (11.4% of total neutral
      glycolipids), GalCer (21.5%), LacCer (21.4%), Gb4 (21.1%), and three unknown
      neutral glycolipids (23%). These unknown glycolipids were characterized as
      Lewis(x) (fucosylneolactonorpentaosyl ceramide; Le(x)),
      difucosylneolactonorhexaosyl ceramide (dimeric Le(x)), and neolactonorhexaosyl
      ceramide (nLc6) by an HPTLC-overlay method for glycolipids using specific mouse
      anti-glycolipid antibodies against glycolipid and/or liquid-secondary ion (LSI)
      mass spectrometry. The ganglioside fraction contained 0.6 micrograms of lipid
      bound sialic acid per mg protein with GD1a as the predominant ganglioside species
      (83% of the total gangliosides) and GM3, GM2, and GM1 as minor components. Trace
      amounts of sialyl-Le(x) and the complex type of sialyl-Le(x) derivatives were
      also present. Immunocytochemical studies revealed that GD1a and GalCer were
      primarily localized on the surface of cell bodies. Interestingly, Le(x)
      glycolipids and sialyl-Le(x) were localized not only on the cell bodies but also
      on short cell processes. Especially, sialyl-Le(x) glycolipid was located on the
      tip of fine cellular processes. The unique localization of the Le(x) glycolipids
      suggests that they may be involved in cellular differentiation and initiation of
      cellular growth in this cell line.

PMID- 8737238
TI  - Cholesterol-containing lactose derived neoglycolipids serve as acceptors for
      sialyltransferases from rat liver Golgi vesicles.
AB  - The cholesterol-containing lactose derived neoglycolipids beta
      Lactosylcholesterol, Cholesteryl-beta-lactosylpropane-1,3-diol, 3-Cholesteryl-1
      beta-lactosylglycerol, 2-Cholesteryl-1-beta-lactosylglycerol, 2,3-Dicholesteryl-1
      beta-lactosylglycerol, 1-Deoxy-1-cholesterylethanolaminolactitol, 1-Deoxy-1
      cholesteryl (N-acetyl)-ethanolaminolactitol, 1-Deoxy-1
      cholesterylphosphoethanolaminolactitol, and 1-Deoxy-1-cholesterylphospho (N
      acetyl)-ethanolaminolactitol were synthesized and used as acceptors for
      sialytransferases from rat liver to Golgi vesicles. Relative activities with the
      neoglycolipids as acceptors varied from 28 to 163% compared to those obtained
      with the authentic acceptor lactosylceramide. Product identification by thin
      layer chromatography and fast atom bombardment mass spectrometry showed that the
      neoglycolipids yielded mono- and disialylated products. The results of
      competition experiments suggested that lactosylceramide and the neoglycolipids
      were sialylated by the same enzymes.

PMID- 8737239
TI  - Treatment of Gaucher disease with an enzyme inhibitor.
AB  - The hypothesis is offered predicting that Gaucher patients could be treated with
      a drug that slows the synthesis of glucosylceramide, the lipid that accumulates
      in this disorder. The present therapeutic approach involves augmenting the
      defective enzyme, glucosylceramide beta-glucosidase, with exogenous beta
      glucosidase isolated from human tissue. This spectacularly expensive mode of
      treatment should be replaceable with a suitable enzyme inhibitor that simply
      slows formation of the lipid and matches the rate of synthesis with the rate of
      the defective, slowly working beta-glucosidase. Several drugs that possess this
      ability are available, the best known of which is 1-phenyl-2-decanoylamino-3
      morpholino-1-propanol (PDMP), a designer inhibitor that resembles the synthase's
      substrate and product. PDMP has been found to be effective in mice, rats, fish,
      and a wide variety of cultured cells. Its use, at suitable dosages, seems to be
      harmless, although long-term tests have not been made. The lack of suitable
      animal models of Gaucher disease has made it difficult to test the hypothesis
      adequately, but PDMP does rapidly lower the levels of glucosylceramide in normal
      animal tissues and the animals evidently do well with the lowered levels of
      glucosylceramide and its more complex glycolipid metabolites.

PMID- 8737240
TI  - Influence of phospholipid chain length on verotoxin/globotriaosyl ceramide
      binding in model membranes: comparison of a supported bilayer film and liposomes.
AB  - The importance of the surrounding lipid environment on the availability of
      glycolipid carbohydrate for ligand binding was demonstrated by studying the
      influence of phosphatidylcholine fatty acid chain length on binding of verotoxins
      (VT1 and VT2c) to their specific cell surface receptor, globotriaosylceramide
      (Gb3) in the presence of auxiliary lipids both in a microtitre plate surface
      bilayer film and in a liposome membrane model system. In the microtitre assay,
      both VT1 and VT2c binding to Gb3 was increased as a function of decreasing PC
      acyl chain length likely resulting in increased Gb3 exposure. In the liposome
      assay VT1 binding was similarly modulated, however the effect of VT2c binding was
      more complex and did not follow a simple function of increased carbohydrate
      exposure. Earlier work established that C22:1 and C18:1Gb3 fatty acid homologues
      were the preferred Gb3 receptor containing liposomes, but in C14PC liposomes,
      binding to C22:1Gb3 (but not C18:1Gb3) was elevated such that this Gb3 species
      now became the preferred receptor for both toxins. This change in verotoxin/Gb3
      homologue binding selectivity in the presence of C14PC did not occur in the
      microtitre bilayer format. These results are consistent with our proposal that
      these toxins recognize different epitopes on the Gb3 oligosaccharide. We infer
      that relative availability of these epitopes for toxin binding in an artificial
      bilayer is influenced not only by the exposure due to the discrepancy between the
      fatty acyl chain lengths of Gb3 and PC, but by the physical mode of presentation
      of the bilayer structure. Such acyl chain length differences have a more marked
      effect in a supported bilayer film whereas only the largest discrepancies affect
      Gb3 receptor function in liposomes. The basis of phospholipid modulation of
      glycolipid carbohydrate accessibility for receptor function is likely complex and
      will involve phase separation, gel/liquid crystalline transition, packing and
      lateral mobility within the bilayer, suggesting that such parameters should be
      considered in the assessment of glycolipid receptor function in cells.

PMID- 8737241
TI  - The effect of fumonisin B1 on developing chick embryos: correlation between de
      novo sphingolipid biosynthesis and gross morphological changes.
AB  - Fumonisins, mycotoxins produced by Fusarium moniliforme and a number of other
      fungi, are potent inhibitors of the sphinganine-N-acyltransferase, a key enzyme
      of sphingolipid biosynthesis, and cause neuronal degeneration, liver and renal
      toxicity, cancer and other injury to animals. In this study we investigated the
      effect of fumonisin B1 on the sphingolipids of developing chick embryos. After
      yolk sac injection of fumonisin B1 a concentration and time dependent increase of
      the sphinganine-over-sphingosine ratio of the embryos could be demonstrated.
      Studies were done to evaluate the effect of fumonisin B1 on the glycophingolipid
      pattern of the chick embryos. In the presence of 72 micrograms fumonisin B1 per
      egg the incorporation of [14C]galactose and of [14C]serine into embryonic
      glycosphingolipids was reduced by about 70%, although the mass of
      glycosphingolipids was not affected by the toxin. However, a reduction of the wet
      weight of the treated embryos was observed. Additionally, histological
      examinations of whole embryo sections of control and fumonisin B1 treated embryos
      are presented. Fumonisin B1 caused haemorrhages under the skin as well as in the
      liver of treated embryos. A close correlation between disruption of sphingoid
      metabolism and light microscopic detectable tissue lesions could be observed.

PMID- 8737242
TI  - Isolation of three novel cholinergic neuron-specific gangliosides from bovine
      brain and their in vitro syntheses.
AB  - In the present study, three extremely minor but novel Chol-1 antigens, termed X1,
      X2, and X3 have been isolated from bovine brain gangliosides. Based on the
      results of sialidase degradation, TLC-immunostaining with anti-Chol-1 antibody
      and fast atom bombardment mass spectrometry, their chemical structures were
      identified as: III6NeuAc-GgOse4Cer (X1: GM1 alpha) III6NeuAc,II3NeuAc-GgOse4Cer
      (X2: GD1a alpha) III6NeuAc,II3NeuAc-NeuGc-GgOse4Cer (X3: GT1b alpha) The yields
      of GM1 alpha, GD1a alpha, and GT1b alpha, were approximately 150, 20, and 10
      micrograms, respectively, from 10 g of the bovine brain ganglioside mixture. In
      conjunction with our previous observations, all gangliosides with anti-Chol-1
      reactivity were found to contain a common sialyl alpha 2-6 N-acetylgalactosamine
      residue, indicating that this unique sialyl linkage is the specific antigenic
      determinant. We subsequently examined the biosynthesis of the three novel Chol-1
      gangliosides using rat liver Golgi fraction as an enzyme source. The results
      showed that GM1 alpha, GD1a alpha, and GT1b alpha were synthesized from asialo
      GM1, GM1a, and GD1b, respectively, by the action of a GalNAc alpha 2
      6sialyltransferase.

PMID- 8737243
TI  - Sulfatide prolongs blood-coagulation time and bleeding time by forming a complex
      with fibrinogen.
AB  - Sulfatides (galactosylceramide I3-sulfate), which are found in serum lipoproteins
      of various mammals, effectively increased prothrombin time (anticoagulant effect)
      and also effectively prolonged bleeding time (anti-platelet effect). When equal
      volumes of a homogeneous micellar solution of sulfatide and fibrinogen in
      phosphate-buffered saline were mixed, an insoluble complex precipitated. Analysis
      of the precipitated complex showed that the molar ratio of sulfatide to
      fibrinogen was about 400:1. These results indicate that the sulfatide micelle
      binds tightly to fibrinogen and thereby interferes with both fibrin gel formation
      (anticoagulant activity) and platelet function.

PMID- 8737244
TI  - Prosaposin and prosaptide, a peptide from prosaposin, induce an increase in
      ganglioside content on NS20Y neuroblastoma cells.
AB  - Prosaposin has been recently identified as a neurotrophic factor eliciting
      differentiation in neuronal cultured cells (NS20Y). In this paper we investigate
      whether prosaposin and its active peptide (prosaptide) may modify the ganglioside
      pattern in neuroblastoma cells. The analysis by high performance thin layer
      chromatography did not reveal qualitative changes in the ganglioside pattern of
      NS20Y cells incubated in the presence of prosaposin, compared to control cells,
      but it did reveal an increase of the content of all three major resorcinol
      positive bands (GM3, GM2, GD1a). Cytofluorimetric and immunofluorescence
      microscopic analysis revealed that the increase of the ganglioside content was at
      the plasma membrane level. These findings suggest that the neurotrophic activity
      of prosaposin on NS20Y neuroblastoma cells might be mediated in part by the
      increase of cell surface gangliosides.

PMID- 8737245
TI  - Total synthesis of glycononaosyl ceramide with a sialyl dimeric Le(x)-sequence.
AB  - The first total synthesis of glycononaosyl ceramide with a sialyl dimeric Le(x)
      sequence 1 is described. Regio- and stereo-selective glycosylations of sialyl
      donors 6,7,8 with the suitably protected Le(x) trisaccharide acceptors 9,10 beta
      were performed to give the expected tetrasaccharides 15 and 21, which were
      converted into the corresponding donors 20 and 22. Boron trifluoride etherate
      promoted glycosylation of 20 with pentasaccharide acceptor 11 afforded
      regioselectively the expected nonasaccharide 23. After replacing benzyl groups of
      23 by acetyl groups, the anomeric acetate was transformed into the alpha
      trichloroacetimidate 27. The crucial coupling between 27 and (2S, 3R, 4E-3-O
      benzoyl-2-N-tetracosanoylsphingenine 3 was executed to afford completely
      protected beta-glycoside 28. Finally, selective cleavage of the methyl ester and
      N,O-deprotection of 28 gave the target ganglioside 1.

PMID- 8737246
TI  - Cloned beta 1,4N-acetylgalactosaminyltransferase: subcellular localization and
      formation of disulfide bonded species.
AB  - Cloned human beta 1,4N-acetylgalactosaminyltransferase (GalNAcT) catalyzes the
      synthesis of the glycosphingolipids GM2, GD2, and gangliotriosylceramide. To
      determine the subcellular location of this enzyme and whether it exists in
      intermolecular disulfide bonded species, we stably transfected Chinese hamster
      ovary (CHO) cells with three myc epitope-tagged forms of the GalNAcT gene: the
      native enzyme; the lumenal domain of GalNAcT fused to the cytoplasmic and
      transmembrane domains of N-acetylglucosaminyltransferase I (GNT); and the
      transmembrane and lumenal domains of GalNAcT fused to the cytoplasmic domain of
      the Iip33 form of human invariant chain in order to retain the enzyme in the
      endoplasmic reticulum (ER). Immunoelectron microscopic analysis with anti-myc
      revealed that GalNAcT/myc was present throughout the Golgi stack, the
      GNT/GalNAcT/myc form was restricted primarily to the medial Golgi cisternae, and
      the Iip33/GalNAcT/myc form was restricted to the ER. Cells transfected with each
      of the three constructs contained high levels of GM2 synthase activity in vitro,
      but only the GalNAcT/myc form and the GNT/GalNAcT/myc forms were able to
      synthesize the GM2 product in vivo. The enzyme produced by all three constructs
      was present in the transfected cells in a disulfide bonded form having a
      molecular size consistent with that of a homodimer or higher aggregate.

PMID- 8737247
TI  - Characterization of novel mono-O-acetylated GM3s containing 9-O-acetyl sialic
      acid and 6-O-acetyl galactose in equine erythrocytes.
AB  - Novel mono-O-acetylated GM3s, one containing 9-O-acetyl N-glycolyl neuraminic
      acid and another containing 6'-O-acetyl galactose, were isolated as a mixture
      from equine erythrocytes, and the structures were characterized by one- and two
      dimensional proton nuclear magnetic resonance (NMR) and fast atom bombardment
      mass spectrometry (FAB-MS). The position of the O-acetyl residue was identified
      by the downfield shift of the methylene protons at C-9 of N-glycolyl neuraminic
      acid (9-O-Ac GM3) and C-6 of galactose (6'-O-Ac GM3) in the NMR spectrum, in
      comparison to the respective non-acetylated counterparts. To confirm the presence
      of 6'-O-Ac GM3, the O-acetylated GM3 mixture was desialylated with Arthrobacter
      neuraminidase, giving 6-O-acetyl galactosyl glucosylceramide, the structure of
      which was estimated by NMR and FAB-MS, together with non-acetylated
      lactosylceramide with a ratio of 1:1.

PMID- 8737248
TI  - GM1 ganglioside modulates prostaglandin E1 stimulated adenylyl cyclase in neuro
      2A cells.
AB  - This study demonstrates modulation by GM1 ganglioside of prostaglandin E1 (PGE1)
      induced cAMP formation in Neuro-2a neuroblastoma cells. Pretreatment of the cells
      with neuraminidase, an enzyme that increases cell surface GM1, resulted in
      significant elevation of PGE1-induced cAMP formation, as did preincubation of the
      cells with nmolar concentrations of GM1. Pretreatment with brain ganglioside
      mixture lacking GM1 had no effect. Cholera toxin B subunit, a specific GM1
      binding ligand, inhibited adenylyl cyclase. When the concentration of exogenous
      GM1 in which the cells were preincubated was increased from nmolar to mu molar
      levels there was a dose-responsive fall off in cAMP elevation, attributed to
      progressive inhibition of adenylyl cyclase by increasing GM1. These results are
      interpreted as indicating modulation of this PGE1 receptor in Neuro-2a cells by
      plasma membrane-localized GM1 in a structure-specific manner.

PMID- 8737249
TI  - Synthesis of deoxygalactose-containing sialyl Le(X) ganglioside analogues to
      elucidate the structure necessary for selectin recognition.
AB  - Sialyl Lewis X ganglioside analogues containing 4-deoxy-, 6-deoxy-, and 4,6
      dideoxy-D-galactopyranose in place of D-galactopyranose have been synthesized.
      Glycosylations of 2-(trimethylsilyl)ethyl 2,6-di-O-benzyl-beta-D
      galactopyranoside and 2-(trimethylsilyl)ethyl beta-D-fucopyranoside with the
      phenyl 2-thioglycoside derivative of sialic acid, using N-iodosuccinimide (NIS)
      trifluoromethanesulfonic acid (TfOH) as the promoter in acetonitrile, gave the
      desired 2-(trimethylsilyl)ethyl sialyl-alpha-2-->3)-beta-D-galactopyranoside and 
      beta-D-fucopyranoside, respectively. The sialylgalactose derivative obtained was
      then modified to 4-deoxy and 4,6-dideoxy derivatives. These were converted, by O
      benzoylation, transformation of the 2-(trimethylsilyl)ethyl group to
      trichloroacetimidates, and introduction of the methylthio group with
      methylthiomethylsilane, into the corresponding glycosyl donors, which were then
      coupled with 2-(trimethylsilyl)ethyl O-(2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl)
      (1->3)-O-(2-acetamido-6-O- benzyl-2-deoxy-beta-D-glucopyranosyl)-(1->3)-2,4,6-tri
      O-benzyl-beta-D- galactopyranoside in the presence of
      dimethyl(methylthio)sulfonium triflate (DMTST). The resulting pentasaccharides
      were each converted to the corresponding alpha-trichloroacetimidates, which, on
      coupling with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol, gave the
      desired sphingosine derivatives. Selective reduction of the azide group, N
      acylation with octadecanoic acid, O-deacylation, and saponification of the methyl
      ester afforded the target compounds.

PMID- 8737250
TI  - Interleukin-3-associated ganglioside GD1a is induced independently of normal
      interleukin-3 receptor in murine myelogenous leukaemia NFS60 cells transfected
      with the interleukin-3 gene.
AB  - The mechanism of interleukin-3 (IL-3) independent cell growth and of IL-3
      associated ganglioside expression was analysed using the IL-3 dependent murine
      myelogenous leukaemia cell line NFS60-I7 and IL-3 gene-transfected sublines. The
      transfected cell lines showed autonomous cell growth, tumorigenicity, and IL-3
      associated ganglioside GD1a expression in spite of their IL-3 production. While
      the parental NFS60-I7 cells did not express significant amounts of GD1a,
      exogenous recombinant IL-3 (rIL-3) was demonstrated to induce IL-3-associated
      ganglioside GD1a expression in NFS60-I7 cells. Furthermore, the growth potential
      of the transfected cells was not blocked by anti-IL-3 antibody and expression of
      GD1a was not affected by anti-IL-3 antibody. These findings suggest that IL-3
      expressed intracellularly by gene transfection might act independently of the
      normal IL-3 receptor on autonomous cell growth and on IL-3-associated GD1a
      expression in murine myelogenous leukaemia NFS60 cells.

PMID- 8737251
TI  - Recognition of the blood group H type 2 trisaccharide epitope by 28 monoclonal
      antibodies and three lectins.
AB  - The patterns of cross-reaction of 30 monoclonal antibodies and three lectins were
      determined by ELISA with 21 ABH, Ii or Lewis related synthetic oligosaccharides
      coupled to bovine serum albumin. At least seven main groups of cross-reactive
      patterns were identified among the antibodies, plus several isolated antibodies
      which had intermediate patterns between two of the main antibody groups. The
      three lectins had different cross-reaction patterns, Galactia tenuiflora was
      different from all the antibodies, Ulex europaeus lectin 1 and Lotus
      tetragonolobus were similar, but not identical to groups III and V of antibodies
      respectively. The anti-H antibodies cross-reacting with A type 2 gave similar
      agglutination scores with all the normal ABO erythrocytes, while the anti-H
      antibodies not cross-reacting with A type 2 reacted with different scores: O > A2
      > A2B > B > A1 > A1B > O(h), suggesting that these antibodies react better with
      the free H epitopes and do not recognize the H in A or B epitopes. Based on the
      ELISA and agglutination results and the lowest energy conformations of each
      oligosaccharide obtained by computer modelling, the most probable oligosaccharide
      surface areas recognized by each antibody main group are illustrated.

PMID- 8737252
TI  - Negative-ion fast atom bombardment and electrospray ionization tandem mass
      spectrometry for characterization of sulfated and sialyl Lewis-type
      glycosphingolipids.
AB  - Structural characterization of sulfated and sialyl Lewis (Le)-type
      glycosphingolipids performed by fast atom bombardment (FAB) and electrospray
      ionization (ESI) mass spectrometry is described. Both FAB and ESI collision
      induced dissociation tandem mass spectrometry (CID-MS/MS) of acidic
      glycosphingolipids allowed identification of the sulfated or sialyl sugar, and
      provided information on the saccharide chain sequence. The negative-ion tandem
      FABMS of sulfated Le-type glycosphingolipids having the non-reducing end
      trisaccharide ion as the precursor can be used to differentiate the Le(a)- and
      Le(x)-type oligosaccharides. The ESI CID-MS/MS of multiple-charged ions provided
      even more detailed structural information, and some of the useful daughter ions
      appeared with higher m/z values than the precursor because of a lower charge
      state. These methodologies can be applied to the structural analyses of
      glycoconjugates with much larger molecular masses and higher polarity, such as
      the poly-sulfated and sialyl analogues.

PMID- 8737253
TI  - Structural characterization of a novel mono-sulfated gangliotriaosylceramide
      containing a 3-O-sulfated N-acetylgalactosamine from rat kidney.
AB  - A novel mono-sulfated glycosphingolipid based on the gangliotriaose core
      structure was isolated from rat kidney. The isolation procedure involved
      extraction of lipids with chloroform/methanol, mild alkaline methanolysis, column
      chromatographies with anion exchangers and silica beads. The structure was
      characterized by compositional analysis, FTIR spectroscopy, methylation analysis,
      1H-NMR spectroscopy and negative-ion liquid secondary ion mass spectrometry
      (LSMIS) using the intact glycolipid and its desulfation product. The two
      dimensional chemical shift correlated spectroscopy provided information on the
      sugar sequence as well as anomeric configurations, and indicated the presence of
      a 3-O-sulfated N-acetylgalactosamine within the molecule. Negative-ion LSIMS with
      high- and low-energy collision-induced dissociation defined the sugar sequence
      and ceramide composition, confirming the presence of a sulfated N
      acetylgalactosamine at the non-reducing terminus. From these results, the
      complete structure was proposed to be HSO3-3GalNAc beta 1-4Gal beta 1-4Glc beta 1
      1Cer (Gg3Cer III3-sulfate, SM2b).

PMID- 8737254
TI  - Expression of neolactoglycolipids: sialosyl-, disialosyl-, O-acetyldisialosyl-
      and fucosyl- derivatives of neolactotetraosyl ceramide and neolactohexaosyl
      ceramide in the developing cerebral cortex and cerebellum.
AB  - The following neolacto glycolipids were identified and their developmental
      expression was studied in the rat cerebral cortex and cerebellum: Fuc alpha 1
      3IIInLcOse4Cer,Fuc alpha 1-3VnLcOse6Cer and (Fuc)2 alpha 1-3III,3VnLcOse6Cer, as
      well as acidic glycolipids, NeuAc alpha 2-3IVnLcOse4Cer [nLM1], (NeuAc)2 alpha 2
      3IVnLcOse4Cer [nLD1], O-acetyl (NeuAc)2 alpha 2-3IVnLcOse4Cer [OAc-nLD1] and
      their higher neolactosaminyl homologues NeuAc alpha 2-3VlnLcOse6Cer [nHM1] and
      (NeuAc)2 alpha 2-3VlnLcOse6Cer [nHD1]. These glycolipids were expressed in the
      cerebral cortex only during embryonic stages and disappeared postnatally. This
      loss was ascribed to the down regulation of the synthesis of the key precursor
      LcOse3Cer which is synthesized by the enzyme lactosylceramide: N
      acetylglucosaminyl transferase. On the other hand in the cerebellum, these
      glycolipids increased with postnatal development due to increasing availability
      of LcOse3Cer. In the cerebellum, only nLM1 and fucosyl-neolactoglycolipids
      declined after postnatal day 10-15, perhaps due to regulation by other
      glycosyltransferases. Also, in the cerebellum, nLD1 and nHD1 were shown to be
      specifically associated with Purkinje cells and their dendrites in the molecular
      layer and with their axon terminals in the deep cerebellar nuclei, similar to
      other neolactoglycolipids shown previously.

PMID- 8737255
TI  - Blood group glycosphingolipid expression in kidney of an individual with the rare
      blood group A1 Le(a-b+) p phenotype: absence of blood group structures based on
      the globoseries.
AB  - Total neutral glycolipid fractions were isolated from kidney and ureter tissue
      obtained at autopsy of an individual of the rare blood group A1 Le(a-b+) p. The
      amount of glycolipids isolated were 3.7 and 2.5 mg g-1 dry tissue weight for the
      kidney and ureter tissue, which is in the range of reference blood group P
      kidneys. Part of the kidney glycolipid fraction was subfractionated by HPLC.
      Glycolipid compounds were structurally characterized by thin-layer chromatography
      (chemical detection and immunostaining with monoclonal antibodies), proton NMR
      spectroscopy and mass spectrometry. Globotriaosyl- and globotetraosyl-ceramides,
      which are the major compounds in kidneys of P individuals, were absent in the p
      kidney, and a comparatively increased amount of monoglycosyl- and
      lactosylceramides was found. A shift to longer fatty acyl chains in the ceramide
      part of lactosylceramides was noted. Elongated globoseries compounds with five to
      seven sugar residues, including the blood group A type 4 chain structure, were
      lacking. A slight increase in neolactotetraosyl- and blood group X pentaglycosyl
      ceramides was noticed. The study confirms an enzymatic block in the conversion of
      lactosylceramide to elongated globoseries compounds in the kidney tissue similar
      to that of erythrocytes of p individuals.

PMID- 8737256
TI  - Use of diethyl squarate for the coupling of oligosaccharide amines to carrier
      proteins and characterization of the resulting neoglycoproteins by MALDI-TOF mass
      spectrometry.
AB  - The 8-methoxycarbonyloctyl glycosides of GlcNAc beta, Gal beta 1-4Glc beta, Fuc
      alpha 1-2Fuc alpha 1-3GalNAc beta and Fuc alpha 1-2Gal beta 1-3[Fuc alpha 1
      4]GlcNac beta were converted to primary amines by reaction with neat
      ethylenediamine and then coupled to bovine serum albumin (BSA) using diethyl
      squarate as the connector. The average degree of incorporation of the sugar onto
      the protein, as well as the molecular weight distribution, could be conveniently
      determined using matrix assisted laser desorption ionization/time of flight
      (MALDI-TOF) mass spectrometry thus avoiding cumbersome structure-dependent colour
      tests or analysis of cleaved ligand. The present coupling method has the
      advantages of proceeding under very mild conditions, yielding controlled
      incorporation values and can reliably be used for the coupling of very small
      amounts (mg) of oligosaccharide.

PMID- 8737257
TI  - Modulation of cholinergic synaptic functions by sialylcholesterol.
AB  - The effects of sialylcholesterol, a synthetic ganglioside analogue, on
      cholinergic synaptic functions were investigated using synaptosomes prepared from
      C57BL/6 mouse brain cortices. Addition of alpha-sialylcholesterol stimulated high
      K (50 mM)-evoked acetylcholine (ACh) release from synaptosomes at concentrations
      ranging from 1 to 5 microM. The beta-anomer of the sialyl compound also increased
      the neurotransmitter release at 5 microM, but the effect was much smaller than
      that of the alpha-anomer. Beta-sialylcholesterol appeared to increase high
      affinity choline uptake and Ach synthesis, resulting in an increment in the
      release of ACh. On the other hand, alpha-sialylcholesterol did not change the
      synthetic rate of ACh, and instead it increased the depolarization=induced influx
      of calcium ions into synaptosomes, while the beta-anomer did not affect the
      divalent cation influx. The enhanced calcium influx is thought to increase ACh
      release from synaptosomes treated with alpha-sialylcholesterol. These results
      imply that the two anomers of sialylcholesterol may modulate the synaptic
      membrane machinery differently, that is, the alpha-anomer may activate voltage
      dependent calcium channels and the beta-anomer may facilitate high-affinity
      choline uptake. In order to evaluate the ameliorating effect of
      sialylcholesterol, alpha-sialylcholesterol was applied to the synaptosomes from
      aged mice (34 months old), which have been shown to have a decreased ACh release
      (Tanaka et al., 1995, J Neurosci Res, in press [1]). The reduced neurotransmitter
      release recovered to the levels of younger animals, suggesting that
      sialylcholesterol might have a potential therapeutic use for restoring synaptic
      function that occurs in aged brains.

PMID- 8737259
TI  - Minister outlines slaughter plans for older cattle.

PMID- 8737260
TI  - Current concepts in the management of canine cataract: a survey of techniques
      used by surgeons in Britain, Europe and the USA and a review of recent
      literature.
AB  - One of the authors (D. L. W.) visited ophthalmologists in Great Britain, Europe
      and the USA to assess current practice in the surgery of cataracts in dogs. This
      paper describes the results of these visits and provides a survey of the
      literature. The success rates in canine cataract surgery have increased markedly
      in the last 10 years, particularly as a result of the introduction of
      phacoemulsification techniques and the reduction in the use of extracapsular
      cataract extraction; these new techniques and the problems they seek to overcome
      are discussed. The paper also considers the developing field of intraocular lens
      implantation, the rationale behind such developments and the benefits and
      potential problems which may occur after the extraction of a cataract and the
      implantation of a lens.

PMID- 8737258
TI  - Programmed cell death in neurotumour cells involves the generation of ceramide.
AB  - Ceramide has been typically thought of as the membrane anchor for the
      carbohydrate in glycosphingolipids but many studies have suggested that it may
      cause apoptosis. Apoptosis or programmed cell death (PCD) is thought to be
      responsible for the death of one-half of neurons surviving the development of the
      nervous system. The potential involvement of the sphingomyelin-ceramide signaling
      process as an integral part of PCD was therefore examined in several neurotumour
      cell lines. We show that synthetic C2-ceramide (N-acetylsphingosine), a soluble
      ceramide analogue, can rapidly trigger PCD in these cells, characterized by: 1)
      classic DNA laddering on agarose gels; 2) DNA fragmentation as determined by
      Hoechst Dye; and 3) cell viability (mitochondrial function and intact nuclei)
      assays. We report that staurosporine can both activate PCD (by all three criteria
      above) in neurotumour cells and increase both the formation of ceramide and
      ceramide mass. Both ceramide formation and the induction of PCD were further
      enhanced by the co-addition of a ceramidase inhibitor oleoylethanolamine (25
      microM). Staurosporine and oleoylethanolamine were similarly effective in
      inducing ceramide formation and PCD in immortalized hippocampal neurons (HN-2)
      and immortalized dorsal root ganglion cells (F-11). Our data suggests that
      formation of ceramide is a key event in the induction of PCD in neuronally
      derived neurotumour cells.

PMID- 8737261
TI  - Changes in the body composition of cats during weight reduction by controlled
      dietary energy restriction.
AB  - Thirteen overweight domestic short-haired cats were fed a commercial low calorie
      diet for 18 weeks at an energy intake to lose weight; they lost an average of
      18.1 per cent of their starting weight. An evaluation of their body composition
      by dual energy x-ray absorptiometry before and after the study suggested that
      most of the weight lost was composed of fat. The cats' lean bodyweight did not
      change significantly, but increased as a proportion of total bodyweight.

PMID- 8737262
TI  - Canine epilepsy: a genetic counselling programme for keeshonds.
AB  - The predisposition of keeshonds (Dutch barge dogs) to an idiopathic epilepsy
      appears to be determined by a single autosomal recessive gene. The pedigrees of
      15 litters which included animals diagnosed as epileptic ('fitters') were
      compared with those of 34 contemporary, normal animals. The pedigrees of all the
      fitters traced back, on both the paternal and maternal sides, to a common
      ancestor. Subsequently, further pedigrees and details of litters were gathered.
      If both parents of a fitter were heterozygous ('carriers'), the progeny (120 in
      number) of all known carrier x carrier matings would be expected to have a ratio
      of three phenotypically normal animals to one fitter, that is, 90:30. The ratio
      observed (91:29) was not significantly different. The Keeshond Club has published
      a list from which the identities of carriers can be inferred, with the intention
      that known carriers should be excluded from breeding. A genetic counselling
      programme has been in operation since 1989, which is based on advising breeders
      on the probability that the offspring of proposed matings would be fitters or
      carriers; advice has been given on 77 proposed matings. The mean probability that
      the proposed matings would result in carriers has declined significantly, and
      this is consistent with a decline in the frequency of the gene for this form of
      epilepsy in the breed.

PMID- 8737263
TI  - Role of chronic disseminated intravascular coagulation in a case of canine
      angiostrongylosis.
AB  - A dog whose major clinical signs suggested a coagulopathy, is described. The dog
      had a history of bleeding episodes and had a severe regenerative anaemia. By
      using specific factor assays, the coagulopathy was found to be due to a
      consumptive intravascular process that resembled chronic disseminated
      intravascular coagulation. Subsequent investigations identified Angiostrongylus
      vasorum as the cause.

PMID- 8737264
TI  - Antibodies in cat sera from southern Africa react with antigens of Ehrlichia
      canis.

PMID- 8737265
TI  - Antigenic type distribution among canine parvoviruses in dogs and cats in
      Germany.

PMID- 8737266
TI  - Economics of warble fly eradication.

PMID- 8737267
TI  - Cyclic neutropenia in collies.

PMID- 8737268
TI  - Teat licking in dairy cattle.

PMID- 8737269
TI  - Flea control in ferrets.

PMID- 8737270
TI  - Low bulk milk SCC and toxic mastitis.

PMID- 8737271
TI  - Dual response modes in lateral geniculate neurons: mechanisms and functions.
AB  - Relay cells of the lateral geniculate nucleus, like those of other thalamic
      nuclei, manifest two distinct response modes, and these represent two very
      different forms of relay of information to cortex. When relatively
      hyperpolarized, these relay cells respond with a low threshold Ca2+ spike that
      triggers a brief burst of conventional action potentials. These cells switch to
      tonic mode when depolarized, since the low threshold Ca2+ spike, being voltage
      dependent, is inactivated at depolarized levels. In this mode they relay
      information with much more fidelity. This switch can occur under the influence of
      afferents from the visual cortex or parabrachial region of the brain stem. It has
      been previously suggested that the tonic mode is characteristic of the waking
      state while the burst mode signals an interruption of the geniculate relay during
      sleep. This review surveys the key properties of these two response modes and
      discusses the implications of new evidence that the burst mode may also occur in
      the waking animal.

PMID- 8737272
TI  - Formation and storage of 11-cis retinol in the eyes of lobster (Homarus) and
      crayfish (Procambarus).
AB  - Modes of storage and mechanisms of formation of 11-cis retinoids in the eyes of
      animals vary widely among the major phyla. We here describe evidence from two
      species of macruran decapod crustacea that point to different processes from
      those known in insects, the other group of arthropods for which there is
      extensive data. The eyes of the lobster (Homarus) contain about 300 pmol of
      retinal, somewhat less free retinol, and variable amounts (up to 1000+ pmol) of
      two retinyl esters, over 90% of which contain retinol in the 11-cis
      configuration. The major ester contains the long chain, polyunsaturated fatty
      acid docosahexaenoate (C22:6), but retinyl oleate (C18:1) is also present.
      Crayfish (Procambarus) contain the same retinyl esters, although in much smaller
      amounts. Homogenates of the eyes of both species are capable of isomerizing all
      trans retinyl docosahexaenoate to the 11-cis configuration without using the
      energy of light. Crude fractionation of homogenates shows isomerase activity
      associated with membranes. The reaction mechanism has not been explored in
      detail, but on the basis of present evidence it may be similar to that found in
      vertebrate pigment epithelium. It is clearly different from the light-dependent
      processes known in insects (Hymenoptera and Diptera) and cephalopod mollusks,
      where isomerization takes place at the level of the aldehyde and 11-cis retinyl
      esters are not present as major storage reserves.

PMID- 8737273
TI  - Selective expression and rapid regulation of GABAA receptor subunits in
      geniculocortical neurons of macaque dorsal lateral geniculate nucleus.
AB  - Monocular deprivation in adult macaques produces a rapid down-regulation in GABA
      and GABAA receptor subunit immunoreactivity in deprived-eye columns of primary
      visual cortex (VI) but a significantly delayed GABA reduction in deprived layers
      of the dorsal lateral geniculate nucleus (LGN). These findings, suggesting that
      normal inhibitory neurotransmission persists in LGN at a time when VI inhibitory
      mechanisms are greatly altered, are consistent with physiological studies that
      have demonstrated a greater degree of functional plasticity in VI than in LGN.
      Nonetheless, functional adaptation to partial loss of visual input has been
      detected in the LGN, indicating that synaptic plasticity takes place in this
      nucleus. In the present study, evidence for early changes in inhibitory
      neurotransmission were examined with immunocytochemical methods to determine if,
      in the absence of early GABA regulation, GABAA receptor subunits in macaque LGN
      are affected by adult deprivation. Immunoreactivity for alpha 1 and beta 2/3
      subunits of the GABAA receptor was intense within the magnocellular layers and
      more modest in the parvocellular layers and intercalated layers. In all layers,
      immunoreactivity was present in the cytoplasm and along the surfaces of
      relatively large somata and in dense tangles of processes in the neuropil. Double
      labeling experiments demonstrated that somata and processes immunoreactive for
      alpha 1 and beta 2/3 were surrounded by GABA terminals but no cell intensely
      immunoreactive for either subunit expressed immunoreactivity for GABA, itself.
      Following periods of monocular deprivation by tetrodotoxin (TTX) injection for 4
      days or longer, layers deprived of visual activity displayed levels of alpha 1
      and beta 2/3 immunoreactivity markedly lower than those displayed by the
      adjacent, normally active layers. Such changes were greater as the period of
      deprivation increased. The changes included a loss of immunostaining in and
      around somata and in many neuropil elements of deprived layers. These data
      indicate that GABA and GABAA receptor subunits alpha 1 and beta 2/3 are expressed
      by separate populations of neurons in macaque LGN that are differentially
      regulated by visual activity. The findings suggest that rapid, activity-dependent
      regulation of postsynaptic receptors represents one mechanism for altering
      synaptic strength in the adult macaque visual system.

PMID- 8737274
TI  - Effects of neurotensin on visual neurons in the superficial laminae of the
      hamster's superior colliculus.
AB  - Autoradiography with 125I-neurotensin in normal and enucleated hamsters was used
      to define the distribution of receptors for this peptide in the superficial
      layers of the superior colliculus (SC). Neurotensin binding sites were densely
      distributed in the stratum griseum superficiale (SGS), and results from the
      enucleated animals indicated that they were not located on retinal axons. The
      effects of neurotensin on individual superficial layer cells were tested in
      single-unit recording experiments. Neurotensin was delivered via micropressure
      ejection during visual stimulation (n = 75 cells), or during electrical
      stimulation of either the optic chiasm (OX; n = 47 cells) or visual cortex (CTX;
      n = 29 cells). In comparison with control values, application of neurotensin
      decreased visual responses of all SC cells tested to 54.1 +/- 34.9% (mean +/-
      standard deviation; range of decrement 7.5 to 100%; nine cells showed no effect
      or an increase in visual activity, which for four of these was > or = 30%).
      Neurotensin application also reduced responses to electrical stimulation of
      either OX or CTX, respectively, to 65.8 +/- 36.5% of control values (range of
      decrement 2.6 to 97.4%; 12 neurons showed a weak increment < or = 30%) and 68.0
      +/- 38.5% (range of decrement 3.3 to 100%; five cells showed no effect or an
      increment, in one case > or = 30%). Of the 25 neurons tested with both OX and CTX
      stimulation, the correlation of evoked response suppression by neurotensin was
      highly significant (r = 0.70; P < 0.001). This suggests that the suppressive
      effects of neurotensin were common to both pathways. To test whether the
      inhibitory effects of neurotensin were presynaptic or postsynaptic, Mg2+ ions
      were ejected iontophoretically to abolish synaptic responses, and the neurons (n
      = 16) were activated by iontophoresis of glutamate and then tested with
      neurotensin. Neurotensin reduced the glutamate-evoked responses to an average
      59.3 +/- 37.9% of control values (range 2.3 to 92.5%; one cell showed an
      increment > 30%). This result suggests that the site of action of neurotensin is
      most likely postsynaptic.

PMID- 8737275
TI  - Microspectrophotometric and immunocytochemical identification of ultraviolet
      photoreceptors in geckos.
AB  - Retinas of the nocturnal geckos, Hemidactylus turcicus, Hemidactylus garnotii,
      and Teratoscincus scincus, were studied with microspectrophotometry and
      immunocytochemistry against various visual pigment epitopes to reveal UV
      sensitive photoreceptors. From 6-20% of the thinner members of type C double
      photoreceptors, earlier believed to be blue-sensitive, were found to contain a UV
      absorbing visual pigment with lambda max at 363-366 nm. The pigment had bleaching
      and dichroic properties typical of other photoreceptor cell types of the retina.
      Presumptive UV-sensitive cells in retinal sections were "negatively" labeled as
      they did not react with either the cone-specific monoclonal antibody COS-1 or
      with the anti-rhodopsin polyclonal serum AO, which together labeled all of the
      remaining photoreceptor types (green-sensitive A singles, B doubles, and thicker
      members of C doubles, as well as the blue-sensitive majority of thinner members
      of C doubles). UV cells were moderately stained with the mAb K42-41 produced
      against the 5-6 loop of bovine rhodopsin, which also moderately labeled blue
      sensitive cells. mAb OS-2 strongly stained all outer segments, including the UV
      sensitive ones. Similarities between gecko UV visual pigments, and UV visual
      pigments of other vertebrates, as well as possible functional significance of
      these cells are discussed.

PMID- 8737276
TI  - Calcium homeostasis in photoreceptor cells of Drosophila mutants inaC and trp
      studied with the pupil mechanism.
AB  - The light-driven pupil mechanism, consisting of an assembly of mobile pigment
      granules inside the photoreceptor cells, has been investigated by in vivo
      reflection microspectrophotometry in wild type (WT) Drosophila and in the
      photoreceptor mutants inaC and trp. The pupillary response of a dark-adapted WT
      eye to a step in light is a monophasic reflectance increase reaching a plateau
      after ca. 15-s light adaptation. This reflectance change is due to photoreceptor
      pigment granules that accumulate near the tips of the rhabdomeres under light
      adaptation and that are withdrawn towards the periphery in the dark (Franceschini
      & Kirschfeld, 1976). The step response of the pupil mechanism of inaC is
      triphasic. Strikingly, the reflectance level at light onset is distinctly higher
      than that in WT, due to a partly aggregated state of the photoreceptor pigment
      granules near the rhabdomere tips that persists in the dark-adapted state, in
      line with direct calcium measurements of Peretz et al. (1994b). The step response
      of the pupil mechanism of inaC is slightly elevated compared to that of WT. The
      step response in trp is a transient, biphasic reflectance change, approximating a
      log normal function. This function is also a good approximation of the pulse
      response in WT and inaC. The intensity range of pupillary sensitivity is about 4
      log unit. The range of inaC compared to that of WT is slightly (approximately 0.5
      log unit) shifted towards lower intensities, but that in trp is strongly shifted
      to higher intensities (approximately 2.5 log unit). The results can be
      interpreted with the present knowledge of the primary steps in fly
      phototransduction and the hypothesis that the local intracellular calcium
      concentration determines the position of the pigment granules, and hence are in
      line with the notion that the pupil can be used as a qualitative Ca2+ probe.

PMID- 8737277
TI  - The effects of luminance and chromatic background flicker on the human visual
      evoked potential.
AB  - Previous studies report that background luminance flicker, which is asynchronous
      with signal averaging, reduces the amplitude and increases the latency of the
      pattern-onset visual evoked potential (VEP). This effect has been attributed to
      saturation of the magnocellular (m-) pathway by the flicker stimulus. In the
      current study, we evaluate this hypothesis and further characterize this effect.
      We found that flicker had similar effects on the pattern-onset and pattern
      reversal VEP, suggesting that the reversal and onset responses have similar
      generators. Chromatic flicker decreased latency of the chromatic VEP whereas
      luminance flicker increased peak latency to luminance targets. This result
      indicates that luminance flicker saturates a rapidly conducting m-pathway whereas
      chromatic flicker saturates a more slowly conducting parvocellular (p-) pathway.
      Finally, evoked potentials to chromatic and luminance stimuli were recorded from
      34 electrodes over the scalp in the presence of static and asynchronously
      modulated backgrounds. An equivalent dipole model was used to assess occipital,
      parietal, and temporal lobe components of the surface response topography.
      Results showed that chromatic flicker reduced activity to a greater extent in the
      ventral visual pathway whereas luminance flicker reduced activity to a greater
      extent in the dorsal visual pathway to parietal lobe. We conclude that the VEP to
      isoluminant color and luminance stimuli contains both m- and p-pathway
      components. Asynchronous flicker can be used to selectively reduce the
      contribution of these pathways to the surface recorded VEP. Our results provide
      evidence of parallel pathways in the human visual system, with a dorsal luminance
      channel projecting predominantly to the posterior parietal lobe and a ventral
      color channel projecting predominantly to inferior temporal lobe.

PMID- 8737278
TI  - Sensitivity to full-field visual movement compatible with head rotation:
      variations with eye-in-head position.
AB  - Variations in velocity detection thresholds for full-field visual rotation about
      various axes are compatible with a simple channel-based system for coding the
      axis and velocity of the rotation (Harris & Lott, 1995). The present paper looks
      at the frame of reference for this system. The head-centered, craniotopic
      reference system and the retinal-based, retinotopic reference systems were
      separated by using eccentric eye positions. We measured the threshold for
      detecting full-field visual rotation about a selection of axes in the sagittal
      plane with the eyes held either 22 1/2 degs up, straight ahead or 22 1/2 degs
      down in the head. The characteristic features of the variation in detection
      thresholds did not stay stable in craniotopic coordinates but moved with the eyes
      and were constant in retinotopic coordinates. This suggests that the coding of
      head rotation by the visual system is in retinotopic coordinates.

PMID- 8737280
TI  - Agrin mRNA expression in the developing chick Edinger-Westphal nucleus.
AB  - Agrin is a large extracellular matrix protein that directs the accumulation of
      acetylcholine receptors at the neuromuscular junction. Recent evidence suggests
      that agrin may be involved in organizing synapses in the visual system as well.
      Focussing on the pathway that controls accommodation and pupilloconstriction,
      this study examined the temporal pattern of agrin expression with reference to
      the organization of cholinergic synapses between embryonic chick Edinger-Westphal
      and ciliary ganglion neurons. In situ hybridization with an S35-labeled agrin
      cRNA probe was used to characterize agrin expression in the Edinger-Westphal
      nucleus during development. Agrin mRNA was detected in the Edinger-Westphal
      nucleus at all time points studied, from embryonic day 7 (E7, Hamburger and
      Hamilton stage 31) through newly hatched chicks. Throughout this period, agrin
      mRNA expression in Edinger-Westphal neurons was lower than in nearby oculomotor
      and trochlear neurons, suggesting that cells projecting to neuronal targets may
      require less agrin than those projecting to muscle. Agrin mRNA expression in the
      Edinger-Westphal nucleus at E7, E8, E9, and E10 was significantly higher than at
      E12. The early appearance of agrin mRNA coincides with the period during which
      acetylcholine receptors are being organized on ciliary ganglion neurons,
      consistent with the possibility that agrin contributes to neuron-neuron synapse
      formation in this pathway.

PMID- 8737279
TI  - Correlation between a bicuculline-resistant response to GABA and GABAA receptor
      rho 1 subunit expression in single rat retinal bipolar cells.
AB  - Using patch-clamp recording in combination with reverse transcriptase-polymerase
      chain reaction (RT-PCR), we show in individual bipolar cells acutely dissociated
      from the adult rat retina a correlation between the expression of the GABAA
      receptor rho 1 subunit mRNA and a bicuculline-resistant, diazepam-insensitive
      component of the GABA-activated whole-cell current response. This "GABAC-like"
      response, contributing to approximately 42% of the GABA-activated whole-cell
      current and displaying variable sensitivity to picrotoxin, was found in bipolar
      cells but not in any of the ganglion cells examined. Expression profiling of
      GABAA receptor subunit mRNAs in individual electrophysiologically tested retinal
      neurons revealed that, while both bipolar cells and ganglion cells may express
      numerous GABAA receptor subunit isoforms, including that of rho 2, the expression
      of the rho 1 subunit was strictly limited to bipolar cells. We propose a possible
      link between the presence of a receptor with GABAC-like pharmacological profile
      and the expression of the retina-specific rho 1 subunit isoform. The results
      presented in this study constitute the first direct demonstration of such a
      correlation at the single-cell level.

PMID- 8737281
TI  - Extra-receptive-field motion facilitation in on-off directionally selective
      ganglion cells of the rabbit retina.
AB  - The excitatory receptive-field centers of On-Off directionally selective (DS)
      ganglion cells of the rabbit retina correspond closely to the lateral extent of
      their dendritic arborizations. Some investigators have hypothesized from this
      that theories for directional selectivity that entail a lateral spread of
      excitation from outside the ganglion cell dendritic tree, such as from starburst
      amacrine cells, are therefore untenable. We show here that significant motion
      facilitation is conducted from well outside the classical excitatory receptive
      field center (and, therefore, dendritic arborization) of On-Off DS ganglion cells
      for preferred-direction, but not null-direction moving stimuli. These results are
      consistent with a role in directional selectivity for cells with processes lying
      beyond the On-Off ganglion cell's excitatory receptive-field center. These
      results also highlight the fundamental distinction in retinal ganglion cell
      receptive-field organization between classical excitatory mechanisms and those
      that facilitate other excitation without producing directly observable excitation
      by themselves.

PMID- 8737282
TI  - Neurotensin induces calcium oscillations in cultured amacrine cells.
AB  - The peptide, neurotensin, is found in a class of amacrine cells synapsing chiefly
      with other amacrine cells in the chicken retina (Li & Lam, 1990; Watt et al.,
      1991). To investigate the possible effects of neurotensin, we have used Ca2+
      imaging to measure cytosolic Ca2+ concentrations in cultured chick amacrine
      cells. Following a delay of about 2 min, neurotensin (300 nM) induced
      oscillations in Ca2+ concentration that typically had a period of 2 min and peak
      values of about 300 nM when averaged over the cell body. The phospholipase C
      inhibitors U-73, 112 and 4'-bromophenacyl bromide terminated oscillations induced
      by neurotensin but the protein kinase inhibitors H7 and staurosporine did not
      inhibit oscillations, increasing their frequency instead. In the absence of
      external Ca2+, neurotensin induced only a single Ca2+ transient, much briefer
      than when external Ca2+ was present. Together these results suggest that
      neurotensin activates phospholipase C, thereby producing IP3 that triggers Ca2+
      release from an internal store. Although this released Ca2+ contributes to
      periodic Ca2+ peaks, the majority of cytosolic Ca2+, even in the first peak,
      comes from Ca2+ influx across the plasmalemma.

PMID- 8737283
TI  - Activation of NMDA receptor-channels in human retinal Muller glial cells inhibits
      inward-rectifying potassium currents.
AB  - Although it is well known that neurotransmitters mediate neuron-to-neuron
      communication, it is becoming clear that neurotransmitters also affect glial
      cells. However, knowledge of neuron-to-glial signalling is limited. In this
      study, we examined the effects of the glutamate agonist N-methyl-D-aspartate
      (NMDA) on Muller cells, the predominant glia of the retina. Our
      immunocytochemical studies and immunodetection by Western blotting with
      monoclonal antibodies specific for the NMDAR1 subunit provided evidence for the
      expression by human Muller cells of this essential component of NMDA receptor
      channels. Under conditions in which potassium currents were blocked, NMDA-induced
      currents could be detected in perforated-patch recordings from cultured and
      freshly dissociated human Muller cells. These currents were inhibited by
      competitive and non-competitive blockers of NMDA receptor-channels. Extracellular
      magnesium reduced the NMDA-activated currents in a voltage-dependent manner.
      However, despite a partial block by magnesium, Muller cells remained responsive
      to NMDA at the resting membrane potential. Under assay conditions not blocking K+
      currents, exposure of Muller cells to NMDA was associated with an MK-801
      sensitive inhibition of the inward-rectifying K+ current (IK(IR)), the largest
      current of these glia. This inhibitory effect of NMDA appears to be mediated by
      an influx of calcium since the inhibition of IK(IR) was significantly reduced
      when calcium was removed from the bathing solution or when the Muller cells
      contained the calcium chelator, BAPTA. Inhibition of the Muller cell KIR channels
      by the neurotransmitter glutamate is likely to have significant functional
      consequences for the retina since these ion channels are involved in K+
      homeostasis, which in turn influences neuronal excitability.

PMID- 8737284
TI  - Cysteamine-induced depletion of somatostatinergic systems alters potentials
      evoked from the rat visual cortex.
AB  - This study was performed in order to establish whether selective depletion of
      somatostatin (SS) in the rat primary visual cortex obtained by cysteamine (CSH)
      administration results in changes of visual evoked potentials (VEPs). VEPs in
      response to a contrast reversal (0.5 Hz) of an optimal sinusoidal grating (0.1
      cycle/deg, contrast 90%, mean luminance 15 cd/m2) were recorded from different
      layers of the binocular portion of the primary visual cortex of anesthetized rats
      with saline injection as well as before and after CSH treatment (90 mg/kg, s.c.).
      VEPs of CSH treated rats, as compared to those obtained either in saline-injected
      animals or before drug administration, are reduced in amplitude at intermediate
      cortical layers whereas they are increased at deeper layers. VEP changes depend
      on CSH treatment and not on the extended anesthesia since no alterations in the
      VEP profile can be observed in saline-injected animals maintained in the same
      experimental condition. Forty-eight hours following CSH treatment, the VEP
      profile is comparable to that of saline-injected animals. Immunocytochemical
      analysis of the visual cortex of rats recorded 7 h after CSH treatment shows a 20
      30% reduction in the number of SS-containing cortical cells. The highest
      reduction can be observed in cortical layer 5 although a significant decrease is
      also found in layers 2-3. In contrast, the pattern of SS immunoreactivity of the
      visual cortex of rats recorded 48 h after CSH administration is similar to that
      obtained in control conditions. These results indicate that a selective toxin for
      somatostatinergic systems induces a transient decrease of SS-containing cell
      number in selected cortical layers. Accordingly, CSH can serve as a useful
      pharmacological tool for the study of somatostatinergic function in the rat
      visual cortex since changes in VEPs can be related to a reduction of
      somatostatinergic neurons associated to CSH treatment. In particular, the present
      results suggest that one of the possible actions of somatostatinergic neurons in
      the rat visual cortex is to modulate the excitatory-inhibitory balance.

PMID- 8737285
TI  - Topography of ganglion cells and photoreceptors in the retina of a New World
      monkey: the marmoset Callithrix jacchus.
AB  - We studied the anatomical substrates of spatial vision in a New World monkey, the
      marmoset Callithrix jacchus. This species has good visual acuity and a foveal
      specialization which is qualitatively similar to that of humans and other Old
      World primates. We measured the spatial density of retinal ganglion cells and
      photoreceptors, and calculated the relative numbers of these cell populations. We
      find that ganglion cells outnumber photoreceptors by between 2.4:1 and 4.2:1 in
      the fovea. The peak sampling density of ganglion cells is close to 550,000
      cells/mm2. This value falls by almost 1000-fold between the fovea and peripheral
      retina; a value which approaches recent estimates of the centroperipheral
      ganglion cell gradient for human and macaque monkey retina and primary visual
      cortex. The marmoset shows a sex-linked polymorphism of color vision: all male
      and some female marmosets are dichromats. Six of the retinas used in the present
      study came from animals whose chromatic phenotype was identified in
      electrophysiological experiments and confirmed by polymerase chain reaction (PCR)
      amplification of cone opsin encoding genes. One animal was a trichromat and the
      others were dichromats. Antibodies against short wavelength-sensitive (SWS) cones
      labeled close to 8% of all cones near the fovea of one dichromat animal,
      consistent with electrophysiological evidence that the SWS system is present in
      all marmosets. The topography and spatial density of cone photoreceptors and
      ganglion cells was similar to that reported for macaque retina, and we found no
      obvious difference between dichromatic and trichromatic marmoset retinas. These
      results reinforce the view that the main determinate of primate foveal topography
      is the requirement for maximal spatial resolution.

PMID- 8737286
TI  - Expression of opsin mRNA in normal and vitamin A deficient retinas of the
      sphingid moth Manduca sexta.
AB  - Two distinct opsin-encoding cDNAs, designated MANOP1 and MANOP2, were isolated as
      3' fragments from the sphingid moth Manduca sexta. They were obtained by reverse
      transcription of retinal RNA and amplification with the polymerase chain reaction
      (PCR) using a degenerate primer designed to an amino-acid sequence conserved in
      arthropod opsins. The cDNA fragments labelled bands at approximately 1.8 kb on
      Northern blots of retinal RNA extracts. Levels of opsin message were compared in
      retinas from normal moths, whose diets were fortified with carotenoid precursors
      of the Manduca rhodopsin chromophore, 3-hydroxyretinal, and those reared on
      carotenoid/retinoid (vitamin A) deficient diets. The chromophore-depleted retinas
      contained more opsin mRNA;this was particularly true for MANOP2. Thus, the
      chromophore is not required for opsin gene transcription in Manduca.

PMID- 8737288
TI  - A model for optokinetic eye movements in turtles that incorporates properties of
      retinal-slip neurons.
AB  - The turtle's optokinetic response is described by a simple model that
      incorporates visual-response properties of neurons in the pretectum and accessory
      optic system. Using data from neuronal and eye-movement recordings that have been
      previously published, the model was realized using algebraic-block simulation
      software. It was found that the optokinetic response, modelled as a simple
      negative feedback system, was similar to that measured from a behaving animal.
      Because the responses of retinal-slip detecting neurons corresponded to the
      nonlinear, closed-loop optokinetic response, it was concluded that the visual
      signals encoded in these neurons could provide sufficient sensory information to
      drive the optokinetic reflex. Furthermore, it appears that the low gain of
      optokinetic eye movements in turtles, which have a negligible velocity storage
      time constant, may allow stable oculomotor output in spite of neuronal delays in
      the reflex pathway. This model illustrates how visual neurons in the pretectum
      and accessory optic system can contribute to visually guided eye movements.

PMID- 8737287
TI  - The optic tract in embryonic hamsters: fasciculation, defasciculation, and other
      rearrangements of retinal axons.
AB  - The early development of the optic tract in hamsters was studied by labeling
      retinal axons with Dil applied to the eye, and then examining the labeled axons
      in flatmount preparations of the rostral brain stem. This technique permits a
      panoramic view of the entire retinal projection, from the chiasm to the caudal
      end of the superior colliculus. In the E11 embryo, retinal axons have reached the
      chiasm. They defasciculate as they emerge from the nerve, prior to reaching the
      ventral midline of the diencephalon, then converge again as they pass over to the
      opposite side. At the midline, many axonal trajectories crisscross, implying some
      shuffling of relative positions. Retinal axons are tightly bundled within the
      optic tract. Upon reaching the ventral border of the lateral geniculate body
      (LGB), they splay out over the nucleus, revealing a wavefront of pioneer axons
      individually distributed across the rostro-caudal extent of the LGB. Later
      emerging retinal axons course over the surface of the thalamus in waves;
      subsequent waves of axons interdigitate between the lead fibers without
      fasciculating along them. Past the LGB, the axons undergo a second change in
      relative positions as the ribbon of fibers swerves caudally, prior to entering
      the superior colliculus. Retinal axons are tipped with growth cones of varying
      morphologies. No strong correlation is evident between the structural complexity
      of the growth cone and its position within the tract. In the majority of cases,
      ipsilaterally and contralaterally directed axons follow a similar developmental
      course along the optic tract, without any indication of a temporal lag in the
      ipsilateral projection as claimed in earlier reports. Understanding the changes
      in spatial distribution of embryonic retinal axons as they navigate along the
      optic tract provides a further step towards elucidating how point-to-point
      projections form in developing sensory systems.

PMID- 8737289
TI  - Gaze field properties of eye position neurones in areas MST and 7a of the macaque
      monkey.
AB  - The activity of parietal cortex neurones primarily related to eye position (EP
      neurones) was studied in macaque monkeys with the aim of precisely defining the
      neurones' gaze fields (GF) and comparing them in two functionally different
      areas, MSTd and 7a. Discharge rates of single neurones in the inferior parietal
      lobule and in the underlying cortex of the superior temporal sulcus were recorded
      in two Java monkeys while the animals fixated a steady visual target positioned
      at several different points on a video screen. The GFs were then drawn as a
      regression surface fitting the mean discharge rates. Cells tonically influenced
      by the angle of gaze were found in both areas. The GFs most often took the form
      of a nearly planar surface best characterized as a ramp tilted towards a
      hemifield or quadrant of the visual field, shifted eccentrically with respect to
      the straight ahead (primary position), and with a midpoint centred between 0 deg
      and 20 deg of gaze eccentricity and saturation between 10 deg and 35 deg. In a
      minority of cases, the discharge rate was nearly maximal at the primary position
      and decreased to a minimum within 35 deg of eccentricity. In other instances, the
      GFs were peaked surfaces, limited to a restricted part of visual space. EP
      neurones, while showing similar gaze fields in areas MST and 7a, were found
      intermingled with functionally different types of cells. The results suggest that
      EP neurones similar to those already described in several areas of the monkey
      parietal cortex are present also in area MST. These cells, by signalling the
      degree of gaze eccentricity from the primary position, encode gaze position in an
      orbito-centered frame extending up to 30-35 deg from the straight-ahead. The role
      of EP neurones might be to supply contiguous elements with a gaze eccentricity
      signal required for visuo-motor processes such as the control of tracking
      movements.

PMID- 8737290
TI  - The role of macrophage subpopulations in autoimmune disease of the central
      nervous system.
AB  - In this review the role of various subpopulations of macrophages in the
      pathogenesis of experimental autoimmune encephalomyetitis is discussed.
      Immunohistochemistry with macrophage markers shows that in this disease different
      populations of macrophages (i.e. perivascular cells, microglia and infiltrating
      blood-borne macrophages) are present in the central nervous system. These
      subpopulations partially overlap in some functional activity while other
      activities seem to be restricted to a distinct subpopulation, indicating that
      these subpopulations have different roles in the pathogenesis of
      encephalomyelitis. The studies discussed in this review reveal that
      immunocytochemical and morphological studies, combined with new techniques such
      as in situ nick translation and experimental approaches like the use of bone
      marrow chimeras and macrophage depletion techniques, give valuable information
      about the types and functions of cells involved in central nervous system
      inflammation. The review is divided in three parts. In the first part the
      experimental autoimmune encephalomyelitis model is introduced. The second part
      gives an overview of the origin, morphology and functions of the various
      subpopulations. In the third part the role of these subpopulations is discussed
      in relation to the various stages (i.e. preclinical, clinical and recovery) of
      the experimental disease.

PMID- 8737291
TI  - Safranin O reduces loss of glycosaminoglycans from bovine articular cartilage
      during histological specimen preparation.
AB  - The ability of Safranin O, added to fixation and decalcification solutions, to
      prevent the escape of glycosaminoglycans (GAGs) from small cartilage tissue
      blocks during histological processing of cartilage has been studied. GAGs in the
      fixatives and decalcifying solutions used and those remaining in the 1 mm3 cubes
      of cartilage were assayed biochemically. The quantity of GAGs remaining in the
      cartilage cubes were determined from Safranin O-stained sections using
      videomicroscopy or microspectrophotometry. A quantity (10.6%) of GAGs were lost
      during a conventional 4% buffered formaldehyde fixation (48 h) and a subsequent
      decalcification in 10% EDTA (12 days) at 4 degrees C. Roughly one-quarter of the
      total GAG loss occurred during the 48 h fixation, and three-quarters during the
      12 days of decalcification. Inclusion of 4% formaldehyde in the decalcification
      fluid decreased the loss of GAGs to 6.2%. The presence of 0.5% Safranin O in the
      fixative reduced this loss to 3.4%. When 0.5% Safranin O was included in the
      fixative and 4% formaldehyde in the decalcification solution, Safranin O staining
      of the histological sections increased on average by 13.5%. After fixation in the
      presence of 0.5% Safranin O, there was no difference in the staining intensities
      when decalcification was carried out in the presence of either Safranin O or
      formaldehyde, or both. It took 24 h for Safranin O to penetrate into the deep
      zone of articular cartilage, warranting a fixation period of at least this long.
      In conclusion, the addition of Safranin O to the fixative and either Safranin O
      or formaldehyde in the following decalcification fluid, markedly reduces the loss
      of GAGs from small articular cartilage explants during histological processing.
      However, for immunohistochemical studies, Safranin O cannot be included in the
      processing solutions, because it may interfere.

PMID- 8737292
TI  - The extracellular matrix proteins fibulin-1 and fibulin-2 in the early human
      embryo.
AB  - Fibulin-1 and fibulin-2, two recently identified extracellular matrix proteins
      with a homologous domain structure, are known to bind various extracellular
      ligands and calcium. In this study, they have been localized at the light
      microscopical level in human embryos of gestational weeks 4-10, using polyclonal
      antibodies. Identical localization patterns were observed for the two fibulins in
      most of the tissues. In the heart, the endocardial cushion tissue and
      endocardium, but not the myocardium, were stained, as were the basement membrane
      zones and adventitia of blood vessels. Staining was also observed in the
      perichondrium and calcifying regions of developing bones. Moreover, reactions
      occurred with the gut subepithelium and epithelial basement membranes of the
      skin. Differences in staining patterns, however, were observed in various neural
      structures. Fibulin-1 was prominent in the matrix of the leptomeningeal anlage,
      in basement membranes of the neuroepithelium and the perineurium of peripheral
      nerves. Fibulin-2 was detected primarily within the neuropithelium, spinal
      ganglia and peripheral nerves. The early embryonic expression of both fibulins
      indicates specific roles during organ development and, in particular,
      involvements in the differentiation of heart, skeletal and neuronal structures.

PMID- 8737293
TI  - Immunocytochemical localization of H(+)-K(+)-ATPase in the rat colon.
AB  - The presence and distribution of gastric-type H(+)-K(+)-ATPase were investigated
      in the rat colon using a monoclonal antibody raised against hog gastric H(+)-K(+)
      ATPase. Rat stomach was used as positive control. Rat kidney and ileum, in both
      of which H(+)-K(+)-ATPase has been reported in the past, were also studied. In
      stomach, very strong staining was found confined to the parietal cells, and a
      strong band at M(r) approximately 94 kDa on the immunoblots. In colon a moderate
      staining was found in the supranuclear region of the epithelial cells, with
      similar intensity and distribution of staining of the surface and deep mucosa of
      the crypts, throughout the length of the colon. Another monoclonal antibody,
      specific to the 31 kDa subunit of H(+)-ATPase, used as a negative control, or
      omission of the primary antibody, resulted in lack of any staining in either
      colon or stomach. On immunoblots of homogenates of colonic mucosa, no specific
      band could be identified, either due to very low expression of the H(+)-K(+)
      ATPase or loss of antigenicity of the epitope during the processing steps. No
      positive staining was observed in rat kidney and ileum, suggesting that they
      contain isoforms that are structurally different.

PMID- 8737294
TI  - Characterization and immunocytochemical localization of actin and fibronectin in
      haemocytes of the mussel Mytilus galloprovincialis.
AB  - Cell-extracellular matrix interactions are recognized to be important for human
      leucocyte functions, including chemotaxis and phagocytosis. These activities
      depend on a reorganization of the microfilament actin (F-actin) promoted by
      fibronectin, one of the major components of extracellular matrices. Although
      invertebrate haemocytes are, in many aspects, similar to the human granulocyte
      monocyte-macrophage cell lineage, actin and fibronectin have not been well
      studied in these cells. Consequently, the characterization and structural
      organization of actin and fibronectin in mussel (Mytilus galloprovincialis)
      haemocytes was investigated using Western blotting analysis, indirect
      immunofluorescence and immunoelectron microscopy. Actin was immunocharacterized
      by an anti-total actin monoclonal antibody. Fibronectin was immunocharacterized
      by an autologous polyclonal antiserum directed against the protein of mussel
      haemolymph. Actin was mainly localized along the peripheral cytoplasm of the
      haemocyte. The distribution of the F-actin microfilaments was assayed with
      Rhodamine-labelled phalloidin. F-actin was associated mainly with stress-fibres
      of spreading haemocytes and with microspikes at the adhesion sites. The labelling
      by the anti-fibronectin antiserum of the haemocyte rough endoplasmic reticulum
      vesicles, revealed by immunoelectron microscopy, suggests that these cells are
      involved in fibronectin biosynthesis. Gold particles were also present along the
      outer surfaces of the cell plasma membrane and its protrusions. Mussel
      fibronectin was localized immunohistochemically at the adhesion sites and in the
      extracellular matrix fibrils. The relationships between fibronectin and the actin
      cytoskeleton in Mytilus galloprovincialis haemocytes are discussed.

PMID- 8737296
TI  - Arylsulphatase A activity and sulphatide concentration in the female rabbit
      oviduct are under physiological hormonal influence.
AB  - Oviduct samples of female rabbits in different phases of the reproductive cycle
      were analysed to establish the role of sex steroid hormones in the regulation of
      sulphatide concentration and arylsulphatase A activity. In addition to
      biochemical procedures, histochemical techniques were used to localize both
      enzyme activity and the natural substrate. The plasma concentrations of
      progesterone and 17 beta-oestradiol were determined by radioimmunoassay (RIA).
      The findings show that the parameters examined undergo considerable changes
      during the different phases of the reproductive cycle. Oestrogens exert an
      inducing action on arylsulphatase A activity, while progesterone inhibits it.
      Fluctuations of the catabolic arylsulphatase activity condition the sulphatide
      concentration, which reaches maximum values at the eighth post-ovulatory day when
      progesterone dominance is consolidated. In this phase of the reproductive cycle,
      thin-layer chromatography confirms the presence not only of larger quantities of
      sulphatides, but also of all other lipid fractions.

PMID- 8737295
TI  - The glucose-6-phosphatase enzyme in developing human trachea and oesophagus.
AB  - Glucose-6-phosphatase is an endoplasmic reticulum system which is found primarily
      in liver and kidney. Recently, it has become clear that it is also present in
      lower amounts in a variety of other tissues. Previous histochemical studies of
      glucose-6-phosphate hydrolysis in trachea have given equivocal results and only
      one study on adult oesophagus has shown glucose-6-phosphatase, enzymatic activity
      but without cellular localization. We have now shown, using microassay
      techniques, that microsomes isolated from human foetal trachea and oesophagus
      both contain low levels of specific glucose-6-phosphatase activity (mean = 0.9
      and 1.5 nmol min-1 mg-1 microsomal protein, respectively) which are less than 10%
      of the levels in microsomes of human foetal liver of similar age. In the
      developing trachea, glucose-6-phosphatase immunoreactivity has been found, using
      a monospecific antibody to the catalytic subunit of the glucose-6-phosphatase
      enzyme, to be first present at 10-11 weeks' gestation, and thereafter in foetal
      life, predominantly present in ciliated cells, with smaller amounts in non
      ciliated secretory cells, duct lining cells, and occasional basal cells. The
      foetal oesophageal epithelium is transiently ciliated from 10 to 11 weeks'
      gestation, but ciliated cells are gradually replaced by squamous cells from 14 to
      16 weeks onwards. Glucose-6-phosphatase immunoreactivity in human foetal
      oesophagus is predominantly confined to ciliated cells, but non-ciliated luminal
      cells are also reactive, as are occasional basal cells. Mucus secretory cells in
      foetal trachea and oesophagus are immunonegative, as is the entire epithelium of
      both organs in the embryo (up to 56 postovulatory days.

PMID- 8737297
TI  - Vaginal birth after cesarean section: current opinion.
AB  - Although the current literature attests to the merits of a trial of labor in the
      patient with a prior cesarean section, some controversies remain. For example,
      can women with two or more sections be allowed a trial of labor and can patients
      who undergo a trial of labor receive oxytocin or prostaglandins for induction?
      Also, do certain indications for previous cesarean section such as relative
      cephalopelvic disproportion/failure to progress or the diagnosis of breech or
      twins in the present pregnancy constitute an indication for elective repeat
      cesarean delivery? These questions along with some other controversies are
      discussed in the light of newly accumulated data in the English literature and
      our own experience over the last decade in a major university-based tertiary
      medical center.

PMID- 8737298
TI  - Prevalence, management and outcome in eclampsia.
AB  - OBJECTIVE: To review the management of eclampsia in our institution. METHOD: The
      prevalence, management and outcome of women with eclampsia over a period of 8
      years were reviewed at our referral medical center. There were 444 patients with
      eclampsia among 5757 deliveries (1 in 12.96 deliveries or 7.71% of deliveries).
      Most of the cases were uneducated and had received no antenatal care. One hundred
      eighty-one cases were nulliparous (40.77%). High parities of more than five were
      observed in 27.93% of cases. A standard magnesium sulfate regimen, similar to
      Prichard's intramuscular regimen, was used. RESULTS: Magnesium sulfate
      effectively controlled the convulsions. The incidence of abdominal delivery among
      397 cases with ante- and intrapartum eclampsia was 50.12%. Perinatal mortality
      was very high (591.47% 0) for all cases. Maternal complications were serious and
      led to maternal death in 42 women (9.46%). CONCLUSION: Eclampsia is still a
      serious obstetric complication particularly in uneducated women who do not
      receive antenatal care.

PMID- 8737299
TI  - Unexplained elevated maternal serum alpha-fetoprotein in singleton pregnancies as
      a predictor of fetal risk.
AB  - OBJECTIVE: The aim of the study was to evaluate the significance of unexplained
      elevated maternal serum alpha-fetoprotein in singleton pregnancies as a predictor
      of fetal risk. METHOD: A retrospective study of 1582 consecutive women who
      attended the antenatal clinic at Oldham and District General Hospital, Oldham,
      UK, over a 6-month period. One hundred pregnant women with elevated serum alpha
      fetoprotein concentrations were classified as the index group and were matched
      against a control group. All the women in the index group underwent amniocentesis
      and detailed ultrasonography. The incidence of antepartum hemorrhage (placental
      abruption and placenta previa), preterm labor and intrauterine growth restriction
      (IUGR) in the two groups was analyzed and the results subjected to X2 analysis.
      RESULTS: None of the patients in the index group had chromosomal abnormalities or
      birth defects. IUGR occurred in 18 (18%) of the index group babies but in only
      four (2%) in the control group (P < 0.0000006). Placental abruption occurred in
      five (5%) in the index group compared with two (2%) in the control group (P <
      0.03), while preterm labor occurred in nine (9%) in the index group compared with
      two (2%) in the control group (P < 0.005). CONCLUSION: Women with unexplained
      elevated maternal serum alpha-fetoprotein are at increased risk of preterm labor,
      antepartum hemorrhage (placental abruption) and IUGR.

PMID- 8737300
TI  - Multivariate analysis of prognostic factors in patients with endometrial cancer.
AB  - OBJECTIVE: The prognostic factors of endometrial cancer are closely correlated. A
      multivariate analysis was carried to compare the importance of each factor.
      METHOD: A multivariate analysis was performed of 19 clinicopathologic prognostic
      factors obtained from 144 endometrial cancer patients who had been surgically
      treated in our hospital between January 1971 and December 1993. RESULTS:
      Significant prognostic factors according to the Kaplan-Meier method were depth of
      invasion, vascular invasion, nuclear grade, cervical involvement, lymph node
      metastases, intraperitoneal cytology, serous adenocarcinoma, DNA ploidy, type of
      hysterectomy and surgery only or combined with chemotherapy or radiotherapy.
      Multivariate analysis showed that vascular invasion and nuclear grade were more
      significant than structural grade, histologic subtype or DNA ploidy. CONCLUSION:
      Multivariate analysis is useful for extracting important recurrent factors from
      mutually related prognostic factors. Vascular invasion and nuclear grade are
      singled out as the most useful histologic prognostic factors.

PMID- 8737301
TI  - Ultrasonographic monitoring of ovarian follicles in women using norethisterone
      for contraception.
AB  - OBJECTIVE: The purpose of this study was to examine the effect of intranasal and
      oral norethisterone (NET) on ovarian folliculogenesis. METHODS: Sixteen healthy,
      sterilized women with regular menstrual cycles were recruited to the study. NET
      300 micrograms per day was administered orally (n = 8) or intranasally (n = 8)
      for two consecutive menstrual cycles. Serial pelvic ultrasonography was performed
      to monitor ovarian follicular growth. RESULTS: Ultrasonographic evidence of
      normal follicular growth and ovulation was observed in 10 cycles whilst 22 cycles
      were anovulatory. Formation of follicular cysts was seen in 14 cycles, 13 of
      which were anovulatory and in one ovulation was observed in the opposite ovary.
      The size of the cysts varied between 27 and 44 mm. The cysts disappeared when NET
      treatment was discontinued. A positive correlation between cyst size and
      estradiol levels was observed with intranasal NET in 50% of cyst cycles. In three
      cycles, although normal follicular growth and endocrine profile were observed,
      the follicles failed to rupture. These were classified as luteinized unruptured
      follicles. Immature follicles < 10 mm were seen in six cycles. CONCLUSION: The
      study showed that NET administered either orally or intranasally evidently
      disturbs normal follicular growth and rupture.

PMID- 8737302
TI  - A national center for sexually abused women in Sweden.
AB  - Sexual violence is a significant global problem. The unequal power between men
      and women is considered to be the main reason for violence against women. Women
      who are exposed to sexual assault are great consumers of medical and social care.
      The Swedish government has reacted to the problem by establishing an expert
      center for battered and raped women. The center has three main tasks: treatment
      in a professional and empathic way; research into and development of medical and
      psychosocial treatment of patients and the underlying causes of sexual violence;
      education and information of the general public.

PMID- 8737303
TI  - The quality of abortion services in Turkey.
AB  - The quality of abortion in Turkey's public sector hospitals is investigated using
      multiple research methods including observations of actual procedures, interviews
      with medical staff and clients, and an inventory of materials and equipment. The
      results suggest that women who obtain abortions in public sector hospitals have a
      higher abortion rate than the general population. They are likely to receive a
      vacuum aspiration with minimal pain control medication. Clinical infection
      control procedures are insufficient, as are interpersonal communication practices
      including counseling on reproductive health issues and providing factual
      information. Links with family planning services are strong and the majority of
      abortion patients who desire family planning receive a contraceptive method,
      either through direct provision of postabortion contraceptives or referral.

PMID- 8737304
TI  - Isolated 'contractions' of the uterine cervix in a patient with incompetent
      cervix.

PMID- 8737305
TI  - Serous cystadenocarcinoma and ovarian teratoma during pregnancy.

PMID- 8737306
TI  - Congenital chloridorrhea.

PMID- 8737307
TI  - Nephrotic syndrome and periodic fever in pregnancy.

PMID- 8737308
TI  - Long-term danazol administration.

PMID- 8737309
TI  - Incidence of invasive mole and choriocarcinoma following partial hydatidiform
      mole.

PMID- 8737310
TI  - ACOG technical bulletin. Induction of labor. Number 217--December 1995 (replaces
      no. 157, July 1991). American College of Obstetricians Gynecologists.
AB  - Induction of labor is a worthwhile therapeutic option when the benefits to either
      the mother or fetus outweigh those of expectant management. A careful explanation
      to the patient of the process and methods is essential, particularly when
      induction is indicated but the cervix is unfavorable for induction. In these
      circumstances, preinduction cervical ripening may be beneficial but has not been
      conclusively demonstrated to reduce the rate of cesarean births. Although
      widespread, the use of serial inductions with oxytocin has not been clearly shown
      to be advantageous.

PMID- 8737311
TI  - ACOG technical bulletin. Dystocia and the augmentation of labor. Number 218-
      December 1995 (replaces no. 137, December 1989, and no. 157, July 1991). American
      College of Obstetricians and Gynecologists.
AB  - The diagnosis of dystocia is currently a leading indication for cesarean delivery
      in the United States. Efforts to identify abnormal labor and correct abnormal
      contraction patterns, fetal malposition, and inadequate expulsive efforts may
      help eliminate many cesarean deliveries without compromising the outcome for
      either mother or fetus. Cesarean deliveries for dystocia should not be performed
      in the latent phase of labor or in the active phase of labor unless adequate
      uterine activity has been achieved. Cesarean deliveries in the second stage of
      labor may be reduced if, after reevaluation of the fetus and pelvis, there is
      potential for correction of uterine forces with oxytocin, correction of
      malposition, operative vaginal delivery, or safe continued observation. Use of
      either a low-dose or high-dose oxytocin regimen is appropriate for augmentation
      of labor. Regardless of the regimen used, oxytocin should be administered by
      trained personnel capable of responding to complications. A physician who has
      privileges to perform cesarean delivery should be readily available.

PMID- 8737312
TI  - ACOG Committee opinion. Second-look laparotomy for epithelial ovarian cancer.
      Number 165, December 1995 (replaces no. 100, November 1991). Committee on
      Gynecologic Practice. American College of Obstetricians and Gynecologists.
AB  - The Committee on Gynecologic Practice makes the following recommendations: Second
      look laparotomy is the most accurate method of assessing disease status in a
      patient who has completed initial therapy for ovarian cancer and who is
      clinically free of disease. It serves as a useful early endpoint in assessing the
      effectiveness of treatments in prospective randomized clinical trials. There are,
      however, no prospective clinical trials that demonstrate an advantage in survival
      for patients who have undergone second-look laparotomy. A negative second-look
      laparotomy is associated with improved survival rates and may be used to justify
      either discontinuing therapy altogether or using an investigational consolidation
      therapy. In patients with stage I or II ovarian cancer who have had complete
      surgical staging and appropriate adjuvant therapy and who are asymptomatic, a
      second-look laparotomy is rarely positive (5%) and is not thought to be of value.
      Retrospective studies suggest that maximal cytoreduction (to nodules < 5 mm) of
      tumors in patients with stage III or IV ovarian cancer who are clinically free of
      disease prior to secondlook laparotomy is associated with improved median
      survival rates despite the lack of evidence that current second-line therapies
      are effective. Second-look laparotomy usually should be performed by a
      gynecologic oncologist who has a complete understanding of ovarian cancer and has
      defined the goals of second-look laparotomy for an individual patient. The
      surgeon must have the surgical skills to perform a complete operation as
      described in the "Assessment" section. Second-look laparotomy is not considered a
      "standard" or "mandatory" operation for all women with ovarian cancer. The
      additional morbidity and cost of the procedure must be weighed against the
      expected benefit for the individual patient. A second-look laparotomy may be
      appropriate based on the goals of treatment for an individual patient or as part
      of a clinical protocol.

PMID- 8737313
TI  - ACOG Committee opinion. Informed refusal. Number 166, December 1995. Committee on
      Professional Liability. American College of Obstetricians and Gynecologists.

PMID- 8737314
TI  - ACOG Committee opinion. Perinatal and infant mortality statistics. Number 167,
      December 1995. Committee on Obstetric Practice. American College of Obstetricians
      and Gynecologists.

PMID- 8737315
TI  - ACOG criteria set. Postterm pregnancy. Number 10--August 1995. Committee on
      Quality Assessment. American College of Obstetricians and Gynecologists.

PMID- 8737316
TI  - ACOG criteria set. Laparoscopically assisted vaginal hysterectomy. Number 11-
      October 1995. Committee on Quality Assessment. American College of Obstetricians
      and Gynecologists.

PMID- 8737317
TI  - ACOG criteria set. Initial maternal--fetal assessment following acute abdominal
      trauma. Number 12--November 1995. Committee on Quality Assessment. American
      College of Obstetricians and Gynecologists.

PMID- 8737318
TI  - Embracing exercise in 'sport' psychology.

PMID- 8737319
TI  - Antecedents of state goals in age-group swimmers: an interactionist perspective.
AB  - A theoretical tenet of 'goal perspective' theory that has received little
      research attention has been the nature of the relationship between the person and
      the environment with respect to predicting task and ego involvement in sport.
      This study therefore integrated both dispositional and situational criteria in
      order to examine their relative ability to predict 'state' goals of task and ego
      involvement in a sample of age-group swimmers (n = 214). The Task and Ego
      Orientation in Sport Questionnaire (TEOSQ) and several single-item assessments of
      goal orientation represented the dispositional measures, and these were completed
      away from the race environment. The situational antecedents of task and ego
      involvement were assessed by the 11-item Race Context Questionnaire (RCQ), which
      was administered to the swimmers within 1 h of their main event at their county
      championships. The RCQ also assessed the extent to which the performer had set
      task and ego goals for the upcoming race (i.e. 'state' goals). Factor analysis of
      the RCQ revealed four factors which cumulatively accounted for 65.3% of the
      variance: social/personal perceptions of ability; perceived state goal preference
      of significant others; race outcome value; and perceived readiness. Moderated
      hierarchical regression analyses revealed separate main effects as well as
      significant interactions between the dispositional and situational predictors of
      the different goal types. Specifically, social perceptions and race-specific
      criteria were the major predictors of ego involvement, whereas the level of task
      orientation combined with the above situational factors seemed to exert greater
      influence in determining the intensity of task involvement in age-group swimmers.
      These findings alert researchers to the importance of applying an interactionist
      perspective to the examination of 'state' goals.

PMID- 8737320
TI  - Electromyographic activity during windsurfing on water.
AB  - Electromyographic activity and the electrocardiogram were recorded during
      windsurfing on the water in six subjects (three females and three males).
      'Beating' and 'reaching' (both with continuous pumping), 'running' and
      'uphauling' were performed in light to moderate winds. The physiological signals
      were transmitted to a shore base by radio telemetry and recorded with
      synchronized video and audio information of movement. Heart rates were similar
      for the beating, reaching and running activities within the individuals, but
      varied between individuals (means of 145 to 173 beats min-1), due to performance
      conditions and related muscle activity levels. During beating and reaching, the
      trapezius, flexor carpi ulnaris, extensor carpi radialis, biceps brachii and
      tibialis anterior were very active, with the gluteus maximus being particularly
      important in beating. Running involved less general muscle activity, though the
      role of the tibialis anterior increased. Differences in technique were identified
      between the subjects, notably in the order of muscle recruitment to participate
      in the activities.

PMID- 8737321
TI  - Electromyographic activity of beating and reaching during simulated boardsailing.
AB  - This study examined the responses of six competitive boardsailors (three males,
      three females) during laboratory-based simulation tasks while the
      electromyographic activity of up to 13 muscles was recorded. A sailboard, mounted
      in a steel frame and resting on a waterbed, allowed simulation of roll and pitch
      movements. Wind force was simulated by attaching the boom to a weight stack with
      a hydraulically controlled buffered release phase. The progression of the
      simulation test was controlled by the sailor copying movements on an edited video
      of each subject boardsailing on the open water. Analysis of individual pumping
      movements for mean peak percentage of maximal enveloped voluntary contraction
      (%MEVC) in 'beating' and 'reaching' showed that muscular activity in the arm
      (flexor carpi ulnaris, extensor carpi radialis and biceps brachii) was greatest
      (66-94% MEVC), with considerable activity (58-75% MEVC) in the deltoid and
      trapezius shoulder muscles, but much less activity in the leg muscles (16-40%
      MEVC). For the combined upper and lower body muscles there was a significant
      difference (P < 0.001) between 'beating' and more physically demanding 'reaching'
      pumping activity. Electromyographic activity was higher than reported previously
      during simulation, reflecting the current dynamic nature of the sport.

PMID- 8737322
TI  - Maximal muscle power output in cycling: a modelling approach.
AB  - This study sought to find the optimal design parameters for a bicycle-rider
      system (crank length, pelvic inclination, seat height and rate of crank rotation)
      that maximise the power output from muscles of the human lower limb during
      cycling. The human lower limb was modelled as a planar system of five rigid
      bodies connected by four frictionless pin joints and driven by seven functional
      muscle groups. The muscles were assumed to behave according to an adapted form of
      Hill's (1938) equation, incorporating the muscle force-length relation. The force
      length relation and the values of length that served as input into the relations
      of the various muscles were defined in the following two ways: (1) the force
      length relation was parabolic, based on the experiment of Woittiez et al. (1984),
      and the length was defined as the whole muscle length; and (2) the force-length
      relation was expressed as a combination of lines, based on the cross-bridge
      theory, and the length was defined as muscle fibre length. In the second
      definition, the joint configurations at which four of the seven muscle groups
      reached optimal length (i.e. the length at which the muscle can exert maximal
      isometric force) were further given in two ways. The first way was consistent
      with a previous study from this laboratory (Yoshihuku and Herzog, 1990); the
      second way relied on unpublished experimental data. The dependence of the average
      power on the design parameters and definitions of the force-length relation and
      muscle length was examined. Maximal average power for one full crank rotation
      with a crank length of 0.17 m was found to be about 1300 W for definition 1 and
      1000 W for definition 2. The average power was more sensitive to changes in
      design parameters in definition 2 than definition 1. The optimal rate of crank
      rotation with a crank length of 0.17 m was 18.4 rad s-1 (176 rev min-1) for
      definition 1 (this value is different from the result of the previous study due
      to revisions in input for two muscle groups), and 15.2 rad s-1 (145 rev min-1)
      and 14.6 rad s-1 (139 rev min-1) for definition 2.

PMID- 8737323
TI  - The role of upper limb segment rotations in the development of racket-head speed
      in the squash forehand.
AB  - In the squash forehand drive, the contribution that each of the upper limb
      segment's anatomical rotations make to racket-head velocity towards the front
      wall (x-direction) during the forward swing and at impact were calculated. Eight
      squash players (3 females, 5 males) capable of hitting a high-performance squash
      forehand drive were filmed at a nominal rate of 300 Hz by two phase-locked
      Photosonics cameras. The three-dimensional displacement histories of 12 selected
      landmarks were then calculated using the direct linear transformation approach
      and three-dimensional individual segment rotations were calculated using vector
      equations. Internal rotation of the upper arm at the shoulder joint (46.1%), hand
      flexion at the wrist joint (18.2%) and forearm pronation at the radio-ulnar joint
      (12.0%) were the major contributors to the mean 30.8 m s-1 x-direction velocity
      of the centre of the racket-head at impact. Pronation of the forearm at the radio
      ulnar joint and extension at the elbow joint both played a significant role in
      generating racket velocity in the period prior to impact.

PMID- 8737324
TI  - Strength diagnosis: the use of test data to determine specific strength training.
AB  - The aim of this study was to determine if pre-training strength and power tests
      could provide data that effectively discriminated between subjects whose cycling
      performance improved considerably from training, from those who did not. Twenty
      active healthy male subjects performed 10 weeks of plyometric or weight training.
      Prior to and at the completion of the training, the following tests were
      performed: (1) a 6-s cycle ride; (2) isokinetic leg extension at 1.05 and 5.24
      rads s-1; and (3) a maximum isometric squat. The subjects in the two training
      groups were separated into those whose cycling performance improved significantly
      as a result of the training (good) and those who did not (poor). The pre-training
      muscular function tests of the good versus poor achievers were then compared,
      individually for each form of training, to determine if they could be used to
      discriminate between the two subject groups. The pre-training isometric data
      effectively discriminated between those individuals who improved their cycling
      performance significantly as a consequence of training and those who did not.
      While this finding has practical implications for the exercise science field,
      further research is required before generally useful normative data can be used
      with confidence to prescribe individual specific training programmes.

PMID- 8737325
TI  - The effect of oral creatine supplementation on the 1000-m performance of
      competitive rowers.
AB  - This study investigated the change in 1000-m simulated rowing performance in two
      matched groups of 19 competitive rowers following a 5-day period of
      supplementation with placebo (CON group) or creatine at a dose equivalent to 0.25
      g creatine monohydrate per kilogram of body mass (BM) (EXP group). Creatine
      uptake was calculated from the difference between the amount fed and the amount
      recovered in urine during each 24-h period of supplementation. Total creatine
      uptake for the EXP group over the 5-day period of supplementation averaged 34.9
      +/- 10.9 g (range 20.1-54.9 g), which equated to 3.54 +/- 0.93 mmol kg BM-1. The
      estimated creatine uptake into muscle was 38.1 +/- 10.0 (range 22.6-56.6) mmol kg
      dry weight-1 for these subjects. After supplementation with placebo, the CON
      group showed no change in 1000-m rowing performance (214.0 +/- 30.9 vs 214.1 +/-
      31.5 s; P = 0.88). Of these subjects, 7 decreased and 10 increased their
      performance times (range - 3.1 to 2.7%). By contrast, 16 of the 19 subjects in
      the EXP group improved their performance times. The mean improvement in rowing
      performance for the EXP group was 2.3 s (211.0 +/- 21.5 vs 208.7 +/- 21.8 s; P <
      0.001), an overall improvement of just over 1% (range - 0.4 to 3.4%). We conclude
      that in competitive rowers, a 5-day period of creatine supplementation was
      effective in raising whole-body creatine stores, the magnitude of which provided
      a positive, though statistically non-significant (r = 0.426, P = 0.088),
      relationship with 1000-m rowing performance.

PMID- 8737326
TI  - Factors associated with home advantage in English and Scottish soccer matches.
AB  - Using the results from the end-of-season (1992-93) league tables, overall home
      advantage was confirmed in the eight major divisions of the English and Scottish
      football leagues. The degree of home advantage was found to vary significantly
      across the divisions. Furthermore, these divisional differences in home advantage
      were found to be significantly associated with the mean attendance of each
      division. In an attempt to understand these findings, every occurrence of two
      influential events (either a sending-off or penalty scored) reported in a
      national Sunday newspaper was recorded. The overall frequency of both sendings
      off and penalties scored favoured the home side, but again this was not constant
      across the divisions. In divisions with large crowds, the percentage of home
      sendings-off was relatively small (30%), compared with no difference (50%) in
      divisions with smaller crowds. Similarly, the percentage of penalties scored by
      home sides in divisions with the largest crowds was large ( > 70%), in contrast
      to little or no advantage in divisions with smaller crowds. Two possible
      explanations for these findings were proposed. Either larger crowds were able to
      provoke the away player into more reckless behaviour (real fouls), or influence
      the referee into believing that the away player had committed more fouls
      (perceived fouls).

PMID- 8737327
TI  - Historical developments in gay health and medicine.

PMID- 8737328
TI  - Idiopathic ulcerations of the oesophagus in HIV-infected patients: a review.
AB  - A clinical syndrome of large ulcerations of the oesophagus had been well
      described in the literature in HIV-infected patients. These patients are markedly
      symptomatic with odynophagia and substernal chest pain as their most common
      presenting symptoms. Weight loss often accompanies this disorder. Despite biopsy
      evaluation for patients with idiopathic oesophageal ulcerations, no identifiable
      cause of this lesion is found. Although some authors suggest that these
      ulcerations represent a primary HIV infection of the oesophagus, other question
      the role of HIV itself in the development of these lesions. Patients with this
      disorder appear to respond to corticosteroid therapy in the oral, intravenous or
      intralesional form. This therapy could possibly predispose to infectious
      complications. Acute HIV infection has also been described presenting with
      lesions of the oesophagus which may be single or multiple. It has again been
      suggested that HIV is the primary aetiology of the oesophageal ulcerations.
      Endoscopic evaluation is mandatory for the diagnosis of idiopathic oesophageal
      ulcerations of the oesophagus in HIV-infected patients. It is important to rule
      out the many other causes of oesophageal ulcerations in these patients, as
      treatment modalities are determined by proper diagnosis of the underlying
      disorder.

PMID- 8737329
TI  - Venous thrombosis in HIV infection.
AB  - Previous reports indicate that venous thrombosis is an infrequent problem in
      patients with HIV infection. Despite this, various HIV-related factors have been
      proposed as potentially thrombogenic and an HIV-related hypercoagulability has
      been suggested. At the present time, there exists no consensus of opinion
      regarding prophylaxis against venous thrombosis for hospitalized patients with
      HIV. This article aims to provide an overview of venous thrombosis in HIV
      infection with particular reference to published and personal evidence for
      possible risk factors and their implications for prophylaxis.

PMID- 8737330
TI  - Commissioning genitourinary medicine services: the policy research agenda.

PMID- 8737331
TI  - Practical models for the care of HIV and AIDS patients.
AB  - Mathematical models for infectious diseases are of limited use in providing
      practical help to health professionals. In this paper we discuss computer models
      developed jointly by operational research mathematicians and clinicians to meet
      this need. We use the term 'operational modelling' to describe this pragmatic
      approach. The models can aid decision-making at a resource planning level and can
      also be used by clinicians to monitor and improve patient care. The models
      incorporate uncertainty and variability and are therefore mathematically complex,
      but are easy to use and provide a great deal of useful information about
      morbidity and resource use.

PMID- 8737332
TI  - Colposcopy services provided by Genito-Urinary Medicine clinics in the United
      Kingdom--British Society for Colposcopy and Cervical Pathology/National Co
      ordinating Network Survey, 1993.
AB  - Postal questionnaires were circulated to all Genito-Urinary Medicine (GUM)
      clinics in the UK (in parallel with questionnaires circulated to gynaecologists)
      on behalf of British Society for Colposcopy and Cervical Pathology (BSCCP) and
      National Co-ordinating Network (NCN) to audit colposcopy services. Information
      was sought on colposcopy workload, referral criteria, treatment method and
      followup, waiting times, staffing and training. A similar but less comprehensive
      survey of colposcopy services in GUM was undertaken in 1990 enabling direct
      comparison of some but not all aspects of the service in the last 3 to 4 years.
      One hundred and forty-two GUM Clinics replied. Of those who replied, 70 (49.3%)
      clinics provided a colposcopy service; an increase from 60 to 70 clinics since
      1990. However, only 66 clinics provided detailed information for analysis. Forty
      six out of 66 (69.7%) clinics performed treatment for some or all of their
      patients and the most frequent methods of treatment used were loop excision and
      cold coagulation. One hundred and seventy-two (range 8-1982) patients were seen
      per annum with a mean of 7 (range 1-68) colposcopy sessions per month. Sixty-four
      per cent of these sessions were undertaken by consultants, 14% by training grades
      and the rest by Clinical Assistants and Associate Specialists. Fifty-three per
      cent of all patients with abnormal smears were colposcoped within 2 weeks and the
      maximum waiting period was less than 8 weeks for all severe dyskaryosis/malignant
      cells cytology reports; 1.6% of clinics admitted to having cases of invasive
      cervical cancer following previous treatment of cervical intraepithelial
      neoplasia (CIN) and 96% of clinics had a protocol in place for defaulters. The
      default rate was 12% both for new and follow-up patients. Thirty out of 70 (43%)
      clinics were computerized and 50/66 (75.8%) of clinics collected accurate
      statistics.

PMID- 8737333
TI  - Access to genitourinary medicine services by women attending a family planning
      clinic.
AB  - The purpose of this study was to assess the need for genitourinary medicine (GUM)
      referral in family planning clinics (FPC) and to investigate whether women were
      more likely to attend an appointment if the consultation took place in the FPC or
      in the GUM clinic. A total of 98 women were referred from the FPC for GUM
      testing. They were randomly referred to be tested either in a local FPC or in the
      local GUM clinic. Sixty-three per cent of the 49 women randomized to be tested in
      the GUM clinic attended the consultation compared to 83% of the 49 women who
      attended the consultation in the FPC. This was statistically significant (P <
      0.05). Twenty-six per cent of those attending the GUM clinic for testing and 29%
      of those women attending the FPC had a sexually transmitted disease (STD), that
      is, excluding candidiasis and bacterial vaginosis. There was no statistical
      difference between the 2 groups. Full GUM testing was successfully carried out in
      the FPC setting. This study showed that women were less likely to attend for GUM
      testing if the consultation took place in the GUM clinic compared to the FPC. It
      is known that there is a need for GUM services to be accessible to FPC attenders
      (and vice versa). Further research is needed to determine why women are reluctant
      to attend GUM clinics.

PMID- 8737334
TI  - An evaluation of percutaneous endoscopic gastrostomy feeding in AIDS.
AB  - Between October 1991 and October 1993, 17 AIDS patients (14 intravenous drug
      users, 3 sexually acquired) were commenced on percutaneous endoscopic gastrostomy
      (PEG) feeding in St James's Hospital. Indications were progressive weight loss
      related to severe anorexia, persistent oesophageal candidiasis (5) and absence of
      gag reflex (1). Two patients requested PEG tube removal after one week because of
      crampy abdominal pain without peritonitis. Five patients died from AIDS related
      infections within 6 weeks of PEG insertion. Ten patients were followed up for > 2
      months (mean 5.2 months, range 2.5-15.5 months). In these 10 patients, 1 patient
      developed a PEG site infection which responded to topical antibiotics. There were
      no other complications. There was a significant (P < 0.001) increase in energy
      and protein intake at 2 months. Variant degrees of weight gain occurred in all
      patients (mean 2.6 kg) (P < 0.01). Small but significant increases in other
      anthropometric variables occurred. Patients who died within 6 weeks of PEG
      insertion were older, and had a lower serum albumin than the group who survived >
      2 months (P < 0.01). A self-administered questionnaire demonstrated that the
      majority of patients found PEG feeding acceptable and preferable to nasogastric
      (NG) feeding.

PMID- 8737335
TI  - Clinical features of early HIV in the Edinburgh City Hospital cohort.
AB  - In order to describe the clinical features of HIV (non-AIDS), particularly
      injection drug use (IDU) related HIV, in patients attending the Regional
      Infectious Diseases Unit in Edinburgh, a prospective review utilizing the WHO
      staging system of the 680 HIV positive patients, 30% of whom were women and 68%
      were infected via IDU, was undertaken. Despite the fact that the majority of drug
      users and heterosexuals enrolled asymptomatic, by 1993, 71% of the patients had
      developed some HIV related clinical problem. The important clinical problems
      observed for the cohort were; minor skin problems, minor bacterial infections,
      major bacterial sepsis, oral thrush, oral hairy leucoplakia, significant weight
      loss of > 10%, HIV related thrombocytopenia and of course AIDS. Unlike previous
      reports from other areas, in Edinburgh drug users were not more likely than other
      risk groups to develop severe bacterial disease. Differences in morbidity and
      mortality rates by risk group but not by gender were noted but these may well be
      affected by the very different enrolment pattern observed in the various risk
      groups. The pre-AIDS mortality rates for drug users were remarkably similar to
      published rates from other centres.

PMID- 8737336
TI  - Laboratory-based HIV surveillance with information on exposure: importance of
      discriminating person-based from test-based results.
AB  - Within a surveillance programme in a Regional Public Health Laboratory anonymous
      information on HIV test, requesting physician and tested individual is
      automatically selected, regardless of test result. Thereby, personal identifiers
      are transformed into unique but meaningless numeric codes. Besides, requesting
      physicians receive a questionnaire on indication for testing (response 87%).
      Between April 1989 and June 1993 12,219 HIV tests were performed in 10,972
      individuals. The percentage of positive tests (2.1%) was twice the percentage of
      positive individuals (1%). No increase in number of new infections was observed
      over time. Of individuals, 41.6% were tested due to third party requests (mainly
      insurance): HIV was demonstrated once (0.03%). Among the remainder, with medical
      indications, seroprevalence was 1.4%. At relatively little expense, we were able
      to provide valid information about patterns of HIV-testing and HIV
      seroprevalences among people tested in routine medical practice. Prevention of
      double counts proved to be important. Extension to other Dutch areas is expected.

PMID- 8737337
TI  - HIV-1 infection in a Ugandan town on the trans-African highway: prevalence and
      risk factors.
AB  - All adult residents (aged 13 years or more) of 154 randomly selected households
      in 3 urban and one semi-rural ward of a town in South West Uganda on the trans
      African highway were invited to participate in a socio-demographic, behavioural
      and medical survey. An unambiguous HIV-1 serostatus was obtained for 389 (80%)
      adults. The overall sero-prevalence rate was 40.4%; all age groups except males
      aged 13-19 years had infection rates in excess of 20%. Rates above 50% were found
      in females aged 20-34 years and males aged 35-44 years. For females
      seropositivity rates increased steeply with increasing numbers of lifetime sexual
      partners up to a maximum of 3; in contrast, for males rates continued to increase
      with increasing numbers of partners. The risk of infection amongst those with
      only one reported partner was 17%. A high proportion of males (14%) and females
      (18%) reported a history of genital ulcer disease within the previous 6 months;
      on examination genital lesions were observed in 12% of all participants.
      Interventions with a single focus are unlikely to have much impact in such a
      situation and a strategy is suggested which includes 3 components, namely
      improved STD control, a reduction in partner change and an increase in condom
      utilization.

PMID- 8737338
TI  - Is Trichomonas vaginalis still a marker for other sexually transmitted infections
      in women?
AB  - Trichomonas vaginalis (TV) has, in the past, been regarded as a useful marker for
      other asymptomatic sexually transmitted infections such as gonorrhoea and
      chlamydia in women. The aim of this study was to determine whether TV is still
      such a marker. All women attending the Department of Genito-urinary Medicine at
      the Leeds General Infirmary with a diagnosis of TV during 1983 and 1993 were
      identified and concurrent infections were tabulated. In 1993 approximately 30% of
      women with TV had at least one other sexually transmitted infection. The
      prevalence of gonorrhoea in women with trichomoniasis fell from 20% in 1983 to
      10% in 1993 whilst the prevalence of chlamydia in these women remained unchanged
      at 15%. Thus trichomoniasis is still frequently associated with other pathogens
      in women and screening of these women for other infections remains essential.

PMID- 8737339
TI  - A case of acute hepatitis B occurring four months after multiple rape.

PMID- 8737340
TI  - Non-specific urethritis--possible association with isotretinoin therapy.

PMID- 8737341
TI  - The British Postgraduate Medical Federation course in GU medicine/STDs, HIV
      infection and sexual health.

PMID- 8737342
TI  - HIV seropositivity and the breakdown of heterosexual relationships in north west
      London.

PMID- 8737343
TI  - Multiple sites for the detection of Chlamydia trachomatis in women--does it
      matter?

PMID- 8737344
TI  - Trimethylamine and the amine 'wiff' test not related in bacterial vaginosis.

PMID- 8737345
TI  - HIV at the hospital/general practice interface: bridging the communication
      divide.

PMID- 8737346
TI  - Some views of psychic reality.
AB  - This paper is based on the Presidential Address given at the end of the San
      Francisco Congress in August 1995. The author concentrates on discussing the
      three main Panel presentations on psychic reality from the technical, clinical
      and theoretical perspectives and in the context of the life cycle. Referring to
      Grinberg's introduction to the Congress, he reiterates that psychic reality forms
      the central point from which psychoanalysis can be contemplated. A special
      mention is given to the Panel on multidisciplinary perspectives of psychic
      reality, which includes contributions from two well-known philosophers, in
      connection with the current epistemological status of psychoanalysis in the
      context of the Congress's main theme. The author concludes by quoting a sonnet,
      which he feels illustrates the complex dialectic between reality and fantasy,
      between truth and lies.

PMID- 8737347
TI  - Myth and madness: a report of a psychoanalytic study of antisemitism.
AB  - This essay reports the findings and conclusions of a psychoanalytic study of
      antisemitism based upon case reports and classical, historical and literary
      documents. With respect to antisemitic sentiments, individual dynamics are
      overridden by stereotypical myths. After the definitive secession of early Jewish
      and Gentile Christ followers from the Jewish community at the end of the first
      century Common Era, the Jews were stigmatised and demonised by them and by the
      early Church fathers and labelled as a principle of evil, along with Satan, that
      was to blame for all Christian misfortune. The many antisemitic myths that
      evolved throughout the history of the Christian West all concurred in this theme.
      Apocalyptic thinking required such a principle as the source of the death phase,
      so that the elimination of Jews became the condition for the rebirth phase. In
      the presence of a sense of disorganization and chaos, societies congeal into
      fundamentalist groups that require a mythic enemy. These groups tend to cultivate
      apocalyptic paranoia. Under those circumstances, anti-Jewish sentiment and
      discrimination become active persecution. The essay, and to a much greater
      extent, the book upon which it is based, examine some of the findings of the case
      studies, analyse apocalyptic thinking and describe the psychology of the
      fundamentalist community.

PMID- 8737348
TI  - Psychic reality--a personal view of the San Francisco Congress.

PMID- 8737349
TI  - Psychic reality and clinical technique.

PMID- 8737350
TI  - Psychic reality in borderline conditions.

PMID- 8737351
TI  - The patient's psychic reality.

PMID- 8737352
TI  - The psychoanalytic status of social reality.

PMID- 8737353
TI  - Psychic reality and perversions.

PMID- 8737354
TI  - Who maps psychic reality?

PMID- 8737355
TI  - Psychic reality and dreams.

PMID- 8737356
TI  - Hysteria one hundred years on.

PMID- 8737357
TI  - Psychic reality: theoretical concepts.

PMID- 8737358
TI  - The concept of psychic reality in the different theoretical currents of today.

PMID- 8737359
TI  - Psychic reality and the analyst: the inner working of the analyst's mind.

PMID- 8737360
TI  - Psychic reality: its relationship to defences involving negative mechanisms.

PMID- 8737361
TI  - Psychic reality and creativity.

PMID- 8737362
TI  - Addressing the psychic reality of the borderline child.

PMID- 8737363
TI  - Psychic reality and the psychoanalysis of the adolescent.

PMID- 8737364
TI  - The expression of emotions: a contemporary psychoanalytic perspective.

PMID- 8737365
TI  - Psychic reality and the life cycle: the psychic reality of women.

PMID- 8737366
TI  - Infertility, surrogacy and the new reproductive techniques: psychoanalytic
      perspectives.

PMID- 8737367
TI  - Psychic reality and the Freud-Ferenczi controversy.

PMID- 8737368
TI  - Psychic reality and pathogenic beliefs: patients' theories about themselves and
      the relational world.

PMID- 8737369
TI  - The holocaust and beyond.

PMID- 8737370
TI  - A brief history of the International Psychoanalytical Association.
AB  - Originally prepared as part of the background material for an International
      Psychoanalytical Association Symposium devoted to a critical consideration and
      review of the structure and functioning of the IPA in 1988, this paper uses
      sources within the IPA's Archives to trace the key developments in their history
      since their foundation in 1910. An addendum provides some details of similar
      developments from 1985 to the present.

PMID- 8737371
TI  - Multiple transcription start sites for the GnRH gene in rhesus and cynomolgus
      monkeys: a non-human primate model for studying GnRH gene regulation.
AB  - In humans, transcription of the gonadotropin-releasing hormone (GnRH) gene can be
      initiated at two transcription start sites to produce different GnRH mRNAs. The
      upstream transcription start site is used only in reproductive tissues and
      tumors. To determine if a similar pattern of GnRH gene expression exists in non
      human primates, we cloned GnRH cDNA from rhesus monkey hypothalamic RNA using
      reverse transcriptase-polymerase chain reaction (RT-PCR) and the 5' flanking
      region of the monkey GnRH gene by PCR. A 96% similarity between monkey and human
      GnRH cDNA was found with 94% similarity in the upstream promoter region. An
      upstream transcriptional start site, was identified in cynomolgus monkey
      testicular mRNA, 504 base pairs upstream from the hypothalamic site, which was
      different from that identified in the human GnRH gene. Various cynomolgus monkey
      reproductive tissues were found to utilize this upstream transcriptional start
      site. In contrast, no evidence was found for the use of upstream transcriptional
      start sites in rat testis or placenta, suggesting that the reproductive tissue
      specificity of the upstream transcription start site may be a primate specific
      feature.

PMID- 8737372
TI  - Prolactin recruits STAT1, STAT3 and STAT5 independent of conserved receptor
      tyrosines TYR402, TYR479, TYR515 and TYR580.
AB  - The present study of prolactin (PRL) receptor-mediated recruitment of signal
      transducers and activators of transcription (STATs) demonstrates that PRL
      activates STAT3, in addition to STAT1 and STAT5 as previously reported, and that
      STAT1, STAT3 and STAT5 are mediators of PRL effects in cells whether of lymphoid,
      myeloid or mammary epithelial origin. Furthermore, receptor mutants M240 and T280
      that do not mediate PRL-induced JAK2 activation and cell proliferation, are also
      unable to mediate STAT activation, supporting the proposed model of JAK2 as the
      initial effector protein used by PRL receptors. On the other hand, tyrosine
      phosphorylation analysis and electrophoretic mobility shift assays showed that
      receptor mutant G328, which lacks four of the five conserved cytoplasmic tyrosine
      residues of PRL receptors, retained the ability to activate JAK2 and STAT1, STAT3
      and STAT5. These results support the notion that phosphotyrosyl residues other
      than those of the receptor, i.e., JAK2, are involved in recruiting STAT proteins
      to the activated PRL receptor complex.

PMID- 8737373
TI  - Glucocorticoids stimulate prostaglandin H synthase type-2 (PGHS-2) in the
      fibroblast cells in human amnion cultures.
AB  - The human amnion may be an important source of prostaglandins involved in the
      onset of labour. Glucocorticoids are possible regulators of amnion prostaglandin
      synthesis and have been shown to stimulate the PGE2 output and prostaglandin H2
      synthase (PGHS) activity of human amnion cells maintained in primary monolayer
      culture. There are two known isoforms of PGHS: the constitutively expressed PGHS
      1 and the inducible PGHS-2. Recent studies have shown that the latter isoform is
      induced by glucocorticoids. The amnion consists of a single layer of epithelial
      cells beneath which lies a mesenchymal layer containing fibroblasts and it is not
      known which cell types are responding to glucocorticoids in this manner. In the
      present study, we demonstrate that although both cell types are present in
      culture, PGHS-2 protein and mRNA levels increase exclusively within the
      fibroblasts in response to dexamethasone, while PGHS-1 protein and mRNA levels
      remain unaffected in both cell types. These results suggest that the stimulation
      of PGE2 in cultured amnion cells by glucocorticoids is due to an upregulation of
      PGHS-2 gene transcription in fibroblasts, and that these previously overlooked
      cells may have important roles to play in the synthesis of prostaglandins
      involved in labour.

PMID- 8737374
TI  - CAG-repeat expansion in androgen receptor in Kennedy's disease is not a loss of
      function mutation.
AB  - Expansion of CAG trinucleotide repeats in androgen receptor gene is present in
      patients with a rare X-linked inherited form of motor neuron disorder termed
      Kennedy's disease or spinal and bulbar muscular atrophy (SBMA). This is a late
      onset progressive disease often associated with mild signs of androgen
      insensitivity. Defects in androgen receptor (AR) action have been linked to the
      expansion of the CAG trinucleotide repeats and postulated to be the cause of the
      disease. We have identified a trinucleotide repeat of 45 in the N-terminus of the
      AR in two brothers with SBMA and several members in their family (range in the
      general population is 11-35). Treatment of the patients with androgens failed to
      improve their clinical symptoms and provided no hint of an anomalous function of
      the AR. Consistently, functional analysis of the mutant receptor showed hormone
      binding, transactivation and transrepression potentials identical to that of the
      wild-type receptor. These results together argue against SBMA being a loss of
      function mutation of the AR.

PMID- 8737375
TI  - Isolation of NEB-LFamide, a novel myotropic neuropeptide from the grey fleshfly.
AB  - A methanolic extract of 350,000 adult grey fleshflies Neobellieria bullata, was
      prepared and screened for myotropic activity. After fractionation on the first
      column, all fractions were screened in two heterologous (Locusta oviduct and
      Leucophaea hindgut) and one homologous (Neobellieria hindgut) myotropic bioassay.
      We here report the purification of one fraction, which stimulates the
      contractions of the Locusta oviduct. Electrospray Mass Spectrometry of the
      peptide revealed a molecular mass of 1395.82. The primary structure has been
      determined as AYRKPPFNGSLF-amide. This novel peptide was designated Neb-LF-amide.
      This sequence is different from the other known myotropic peptides in insects.
      The threshold concentration of the synthetic peptide is 1 x 10(-7) M on the
      Locusta oviduct. On the hindgut of Neobellieria or Leucophaea, the synthetic
      peptide is not active. By use of a polyclonal antiserum raised against the
      synthetic peptide, immunoreactivity was localized in median neurosecretory cells
      in the pars intercerebralis of the fly brain, indicating that Neb-LF-amide is a
      neuropeptide.

PMID- 8737376
TI  - The same sequence mediates activation of the human urokinase promoter by cAMP in
      mouse Sertoli cells and by SV40 large T antigen in COS cells.
AB  - Cell-specific activation by follicle-stimulating hormone and its intracellular
      mediator, cAMP, of the human urokinase promoter in mouse Sertoli cells requires
      overlapping purine-rich and GC-rich sequences between -54 and -42 from the
      transcriptional start site. We have previously shown that binding of unidentified
      nuclear factors to these sequences is induced by cAMP stimulation, and that
      sequences from the enhancerless SV40 replication origin can interfere with the
      binding, whereas consensus Sp1 binding sites are ineffective. We now show that
      sequences within the SV40 origin able to compete for the formation of cAMP
      induced DNA-protein complexes in Sertoli cell nuclear extracts are binding sites
      for the SV40 large T antigen. Large T antigen expressed in COS cells binds the
      cAMP-responsive sequences of the human urokinase gene and transactivates the
      proximal promoter, thus mimicking the effect of nuclear factors induced by cAMP
      in Sertoli cells. We show that Egr-1 is one of the factors present in cAMP
      induced DNA-protein complexes formed between the human urokinase promoter and
      Sertoli cell nuclear extracts. However, Egr-1 levels are similar in unstimulated
      and cAMP-treated Sertoli cells, suggesting that this factor interacts with a
      different GC-box binding factor, that we have previously shown to be strongly
      induced by cAMP treatment of Sertoli cells. We propose that SV40 large T antigen
      in COS cells can mimick the action of heterodimers formed in cAMP stimulated
      Sertoli cells between Egr-1 and a cell specific cAMP-induced GC-box binding
      factor.

PMID- 8737377
TI  - Quantitative analysis of pancreatic glucokinase gene expression in cultured beta
      cells by competitive polymerase chain reaction.
AB  - Regulation of glucokinase (GK) gene expression in pancreatic beta cells has been
      poorly investigated, both due to low abundance of the gene and to difficulties in
      cells isolation. The present study describes the establishment of a competitive
      RT-PCR method for quantitative analysis of GK gene. The method has been applied
      to the analysis of GK mRNA expression RIN 1046-38 cells. We have monitored
      modifications of GK mRNA expression after different periods of time in culture
      and we have studied the effect induced by dexamethasone (DEX) treatment. We show
      that the method is very sensitive and requires very low amount of RNA. Data
      demonstrate that GK mRNA expression in RIN cells is reduced as a function of
      passages in culture and that the reduction is positively correlated with the
      decrease of insulin responsiveness observed in high passages cells. DEX treatment
      inhibits GK mRNA expression in RIN cells in a dose-dependent and time-dependent
      manner.

PMID- 8737378
TI  - Lipopolysaccharide-induced DNA damage is greatly reduced in rats treated with the
      pineal hormone melatonin.
AB  - The ability of melatonin to influence lipopolysaccharide (LPS)-induced
      genotoxicity was tested using micronuclei as an index in both bone marrow and
      peripheral blood cells of rats. LPS was given as a single dose of 10 mg/kg.
      Melatonin (5 mg/kg) was injected prior to LPS administration and thereafter at 6
      h intervals to the conclusion of the study (72 h). The number of micronucleated
      polychromatic erythrocytes increased significantly after LPS administration both
      in cells from peripheral blood and bone marrow. Melatonin administration to LPS
      treated rats highly significantly reduced micronuclei formation in both
      peripheral blood and bone marrow cells beginning at 24 h after LPS administration
      and continuing to the end of the study. In blood the increase in micronuclei
      formation was time-dependent in LPS-treated rats with peak values being reached
      at 36-48 h. The ability of melatonin to reduce LPS-related genotoxicity is likely
      related to its antioxidant activity.

PMID- 8737379
TI  - Characteristics of ANP-binding sites in the adrenal capsules of term-pregnant
      rats.
AB  - Significant increases of circulatory volume and plasma aldosterone levels are
      observed in pregnancy. We investigated whether a decrease of atrial natriuretic
      peptide (ANP) receptors in the adrenal zona glomerulosa (ZG) could explain the
      marked elevation of plasma aldosterone occurring during pregnancy. 125I-ANP
      binding was measured in competition experiments using rANP(1-28), ANP(4-23), a
      truncated analog which has high specificity for the ANP-C receptor, or a
      combination of both. Western blot experiments were also performed with an
      investigation into the effect of ANP on aldosterone secretion in adrenal capsule
      suspensions. 125I-ANP binding on adrenal ZG membranes was displaced by ANP(1-28)
      with an affinity (Kd) of 313 +/- 39 and 323 +/- 60 pM (NS) for pregnant and non
      pregnant rats, respectively. The density of sites (Bmax) decreased slightly but
      not significantly during pregnancy. Displacement experiments with ANP(4-23)
      demonstrated a Bmax of 137 and 134 fmol/mg of proteins (NS) for pregnant and non
      pregnant rats, respectively. Studies were performed to block the ANP-C site.
      Displacing the remaining 125I-ANP binding with ANP(1-28) led to an affinity
      constant and receptor density which were not significantly different between the
      two groups of rats. The results obtained with Western blots showed a single band
      of 123 kDa with no significant variations in ANP-R1 receptors in the ZG during
      gestation. The sensitivity of potassium-, ACTH- or angiotensin II-stimulated
      aldosterone secretion to ANP was not altered by gestation. These data show that
      the apparent hyperaldosteronism found in normal term-pregnant rats is not the
      consequence of modifications in the affinity, number and properties of ANP
      receptor types or in the sensitivity of the aldosterone response to ANP.

PMID- 8737380
TI  - Phospho-serine/threonine phosphatases in rat islets of Langerhans: identification
      and effect on insulin secretion.
AB  - Stimulation of insulin secretion is accompanied by changes in the phosphorylation
      state of several islet polypeptides. Protein (de)phosphorylation is mediated by
      the action of protein kinases and phosphoprotein phosphatases. In this study we
      have investigated expression of phospho-serine/threonine phosphatases (PPs) in
      rat islets of Langerhans and studied the role of these enzymes in the regulation
      of insulin secretion. PP1, PP2A and PP2B were identified in rat islets and high
      levels of PP1/2A activities were detected. Inhibition of PP1/2A markedly
      inhibited glucose-stimulated insulin secretion, whilst glucose increased islet
      PP1/2A activities in situ. Insulin secretion at basal glucose was unaffected by
      inhibitors of PP1/2A. Inhibition of PP2B had no effect on either basal or glucose
      stimulated insulin secretion. These results suggest that PP1/2A are stimulated by
      glucose in rat islets and the presence of active PP1/2A is required for
      stimulation of insulin secretion by glucose.

PMID- 8737381
TI  - Paradoxical effect of 3-isobutyl-1-methylxanthine on cytochrome P450 cholesterol
      side-chain cleavage mRNA accumulation in porcine granulosa cells.
AB  - Earlier studies in immature porcine granulosa cells cultured in serum-free medium
      showed dual actions of the protein kinase C activator 12-O-tetradecanoylphorbol
      13-acetate (TPA). In cells incubated for 24 h, TPA inhibited follicle-stimulating
      hormone (FSH)-stimulated cytochrome P450 cholesterol side-chain cleavage
      (P450scc) mRNA accumulation. In contrast, at 4 h, TPA increased P450scc mRNA
      concentration in the absence and presence of FSH or 8-bromo-cAMP; in addition,
      TPA augmented FSH-stimulated cAMP accumulation. The actions of TPA were then
      examined in the presence of the phosphodiesterase (PDE) inhibitor, 3-isobutyl-1
      methylxanthine (IBMX). With IBMX present, TPA caused a smaller relative
      augmentation of cAMP accumulation during a 4-h incubation period, suggesting that
      TPA may both increase cAMP synthesis and inhibit its degradation. The stimulatory
      effect of FSH or 8-bromo-cAMP on P450scc mRNA concentration was not modified by
      IBMX. However, TPA no longer augmented the FSH- or 8-bromo-cAMP-stimulated
      P450scc mRNA accumulation when IBMX was present. In cells treated with FSH for 24
      h, IBMX augmented progesterone production, but paradoxically accentuated the
      inhibitory effect of TPA on steroidogenesis. These results indicate that IBMX
      converts TPA from a stimulatory into an inhibitory agent by an action unrelated
      to cAMP, and points to the need for caution in interpreting experiments with this
      drug.

PMID- 8737382
TI  - Post-translational cooperativity of ornithine decarboxylase induction by
      estrogens and peptide growth factors in human breast cancer cells.
AB  - Mutual interactions between 17 beta-estradiol (E2) and insulin or insulin-like
      growth factor-I (IGF-1) in the regulation of ornithine decarboxylase (ODC)
      expression were examined in estrogen-responsive MCF-7 human breast cancer cells.
      Whereas E2 only retarded the rapid decay of ODC activity observed upon mitogen
      withdrawal, both insulin and IGF-1 led to a rapid (< 4 h), net increase in ODC
      activity that was mediated, at least in part, through their cognate receptors. E2
      synergistically potentiated the induction of ODC by IGF-1, resulting in a 170
      fold elevation of enzyme activity after 48 h, as compared with 23- and 70-fold
      increases caused by E2 and IGF-1 alone, respectively. Cooperativity was more
      pronounced at suboptimal peptide concentrations due to a decrease in the half
      maximal concentration of insulin or IGF-1 required for ODC induction. Phorbol-12
      myristate-13-acetate (PMA) also strongly induced ODC activity in a transient
      manner, and additively to the effect of IGF-1. IGF-1 and PMA additively increased
      ODC mRNA level, whereas E2 alone had no effect on ODC mRNA abundance. IGF-1
      increased the half-life of ODC activity by 60%, whereas E2 or PMA alone had no
      significant effect on enzyme stability. On the other hand, the simultaneous
      addition of IGF-1 and either E2 or PMA cooperatively reduced ODC turnover,
      resulting in 3.5- and 2-fold increases, respectively, in the half-life of ODC
      activity. Thus, ODC expression in breast cancer cells is primarily regulated by
      tyrosine kinase- and protein kinase C-dependent pathways, whereas estrogens
      increase ODC activity through a novel type of synergistic interaction with growth
      factors that results in a decreased rate of enzyme turnover.

PMID- 8737383
TI  - Decreased expression of carboxypeptidase E protein is correlated to estrogen
      induction of rat pituitary tumors.
AB  - Following the cleavage of peptide precursors by endopeptidases such as the
      proprotein convertases PC2 and PC3, carboxypeptidase E (CPE) functions to remove
      basic amino adds from the C-terminus of various pituitary hormones. We
      investigated the role of CPE in the differential sensitivity between rat strains
      to estrogen-induced pituitary tumors. Pituitary CPE protein levels were unchanged
      by diethylstilbestrol (DES) in tumor-resistant Sprague-Dawley (SD) rats. However,
      in tumor-susceptible Fischer 344 (F344) rats, DES decreased CPE protein levels
      such that by 7 and 8 weeks of treatment, CPE was barely detectable. One week
      withdrawal of DES caused an increase in CPE protein levels at 8 weeks. After 2
      and 4 weeks of DES treatment, CPE protein levels in F344 rats decreased to 18 and
      2.3% of control values, respectively, but no strain difference was observed in
      the protein levels of proprotein convertase 2 (PC2) or PC3. Additionally, Brown
      Norway (BN), F344, and F1 hybrid (BN x F344) rats were treated with DES for 10
      weeks. The level of pituitary CPE protein was not affected by DES in BN rats
      whereas F344 rats had only 8% of the level of CPE pituitary protein of BN rats.
      The pituitaries of F1 rats, which had an intermediate weight response to DES, had
      an intermediate level of CPE protein (31% that of BN rats). Levels of CPE mRNA
      were not affected by DES in SD rats while in F344 rats DES tended to decrease
      levels of CPE mRNA after both 2 and 4 weeks of treatment, although the response
      was variable. It thus appears that pituitary CPE protein is differentially
      regulated by DES between tumor-resistant rats and F344 rats primarily at the post
      transcriptional level. Furthermore, in F344 rats, levels of CPE protein are
      inversely correlated to increases in pituitary weight caused by DES treatment.

PMID- 8737384
TI  - Expression of PACAP and its type-I receptor isoforms in the rat ovary.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the
      secretin/glucagon/vasoactive intestinal peptide (VIP)/growth hormone releasing
      hormone (GHRH) family of neuropeptides, several of which stimulate
      steroidogenesis in ovarian granulosa cells. PACAP receptors are of two major
      subtypes; the type I receptor (PACAP-I-R) has much higher affinity for PACAP than
      VIP, and the type II receptor (PACAP-II-R) has similar affinity for both
      peptides. In the rat ovary, expression of the PACAP gene was demonstrated by
      amplification of ovarian RNA by the reverse transcription/polymerase chain
      reaction (RT-PCR). In addition, hybridization of Northern blots of rat ovarian
      poly(A)+ RNA with a 706-nt rat hypothalamic PACAP-I-R cDNA probe revealed the
      presence of a 7.0 kb PACAP receptor transcript, similar to that detected in brain
      and hypothalamus. RT-PCR using specific primers for the PACAP-I-R gene yielded
      products of the expected size with RNA obtained from ovarian tissue, brain, and
      hypothalamus. The authenticity of the PCR products was confirmed by Southern
      blotting and nested PCR, which revealed at least three splice variants of the
      PACAP-I-R in the rat ovary. These findings demonstrate that both PACAP and PACAP
      I-R isoforms are expressed in the rat ovary, where they could exert autocrine or
      paracrine actions on granulosa cell function.

PMID- 8737385
TI  - C-fos and c-jun expression in human endometrium and myometrium.
AB  - Estrogen is a mitogen in human endometrium and is considered to be responsible
      also for myometrial cell proliferation. Signalling pathways of estrogen action in
      these tissues are not known. In various other estrogen responsive cells, estrogen
      induces transient expressions of c-fos and c-jun mRNAs. We examined c-fos and c
      jun mRNA expressions by Northern blotting in paired samples of endometrium,
      myometrium and leiomyoma tissues obtained from women under various hormonal
      environments as well as of endometrium and myometrium at term pregnancy. In
      nonpregnant endometria, strong expressions of c-fos (2.2 kb) and of c-jun (2.7 kb
      and 3.2 kb) were detected both in the follicular and luteal phase of the
      menstrual cycle, and the c-fos expression was significantly stronger in
      proliferative phase endometrium than in the adjacent myometrium. In most of the
      myometrial and leiomyoma tissue samples the signals for both protooncogenes were
      weak, and there were no systematic differences in the expressions between normal
      myometrium and myomatous tissue. In pregnant endometrium and myometrium, both the
      c-fos and c-jun mRNA expressions were nearly undetectable, and in pregnant
      endometrium expressions were significantly lower than those in nonpregnant
      endometrium. Also in late pregnancy myometria, the expression of c-jun was
      significantly lower than in nonpregnant tissues. These data suggest that c-fos
      and c-jun activation may be a part of estrogen-induced signal transduction in the
      endometrium, and that in term pregnancy endometrium this signalling pathway is
      inhibited. Due to the strong expression of c-jun and c-fos both in the
      proliferative and secretory phase endometrium, it is likely that these
      protooncogenes are related to functions other than epithelial cell proliferation
      in human endometrium. The weak expressions of c-fos and c-jun in the myometrium
      and in leiomyomata suggest that signalling pathways mediating steroid hormone
      action in endometrium and myometrium are different.

PMID- 8737386
TI  - Evidence for estrogen receptor-mediated regulation of human gonadotropin
      releasing hormone promoter activity in human placental cells.
AB  - Two fragments of the human gonadotropin-releasing hormone (GnRH) promoter, one
      containing 0.6 kb of the downstream promoter sequence (H-1) and another 1.8 kb
      fragment (H-2) containing the upstream promoter region with a deletion of the
      downstream promoter sequence, were fused to a promoterless luciferase (Luc)
      reporter construct and transfected into the human placental (JEG) cells. JEG
      cells transfected with both constructs showed insignificant changes in luciferase
      activity in response to estradiol. However, cotransfection of H-2-Luc construct
      with a vector expressing a human estrogen receptor (ER) cDNA results in dose
      dependent decreases in luciferase activity in response to estradiol. This ER
      mediated down-regulation of promoter activity was retained in constructs with the
      GnRH promoter deleted to position 548 bp 5' to the upstream transcription start
      site. Further deletion of upstream promoter sequence to 169 bp reversed the
      estrogen responsiveness from inhibitory to stimulatory. Thus, this study
      demonstrated that the upstream GnRH promoter region can be regulated by estrogen
      in transfected JEG cells.

PMID- 8737387
TI  - Mitogenic stimulation of normal and oncogene-transformed human thyroid epithelial
      cells by hepatocyte growth factor.
AB  - Hepatocyte growth factor (HGF) has been shown to be mitogenic for a wide variety
      of epithelial cells, including recently, dog thyroid follicular cells. Here we
      have extended this work to human thyrocytes, and find that recombinant HGF
      stimulates DNA synthesis (proportion of cells in cell cycle S phase) in normal
      primary cells in monolayer, with an ED50 of approximately 8 ng/ml and a maximum
      between 50 and 250 ng/ml. Stimulation was observed even in the presence of 10%
      fetal calf serum (previously the most potent mitogen for these cells in our
      hands), the maximum nuclear 3H-thymidine labelling index achieved with HGF being
      up to 6-fold higher than that with serum alone. A similar additive effect was
      observed on thyrocytes already stimulated to proliferate by expression of an
      activated ret oncogene. These results make HGF the most potent defined mitogen
      for human thyrocytes to date, and suggest that upregulated HGF/met signalling may
      confer a significant growth advantage even in neoplastic thyroid cells,
      consistent with the finding of increased met expression in many thyroid
      carcinomas.

PMID- 8737388
TI  - Microsatellites and PCR primers for genetic studies and genomic sequencing of the
      human TSH receptor gene.
AB  - The thyroid stimulating hormone receptor (TSHR) is the main autoantigen in
      Graves' disease. Mutations of the TSH receptor have been implicated in various
      thyroid diseases. In this study, we describe three polymorphic markers localised
      within introns 2 and 7 of the TSH receptor gene. These markers are useful for the
      study of genetic diseases involving the TSH receptor. They allowed us to map
      precisely the TSH receptor gene on chromosome 14q31 between D14S287 and D14S68.
      We also describe selected primers and experimental conditions for the
      amplification and direct genomic sequencing of the 10 exons of the receptor gene.

PMID- 8737389
TI  - Enteric pathogens associated with gastrointestinal dysfunction in children with
      HIV infection.
AB  - Infants and young children with HIV infection commonly suffer from
      gastrointestinal manifestations of their disease. Many HIV infected children have
      evidence of persistent diarrhoea, malabsorption, malnutrition or growth failure.
      The aetiology and pathogenesis of gastrointestinal dysfunction in HIV infected
      children have not been well defined. We performed immunocytochemical analyses on
      intestinal tissue from 19 HIV-infected children with gastrointestinal dysfunction
      or growth failure. None of these 19 children had microbial pathogens identified
      in faecal samples using standard microbiological methods. Intestinal tissues were
      obtained from the children by biopsy and were examined for antigens from
      Pneumocystis carinii, cytomegalovirus (CMV) and herpes simplex virus (HSV) using
      the avidin-biotin-complex immunohistochemical technique and monoclonal or
      monospecific antibodies. We detected at least one of these pathogens in samples
      from eight (42%) of 19 HIV infected children. P. carinii was the most prevalent
      pathogen, found in five of the eight HIV infected children. All of the children
      with intestinal pneumocystis infection were receiving prophylaxis directed at the
      prevention of pulmonary disease with this organism and none of them were
      undergoing active pulmonary infection. We also identified CMV antigens in
      intestinal tissues from four children and HSV antigens in intestinal tissues from
      one child. Two children were infected with more than one pathogen. On the other
      hand, none of these pathogens were found in the tissues obtained from 10 HIV
      uninfected patients who had intestinal tissues obtained for chronic non
      infectious diarrheal and inflammatory diseases (P < 0.01, Fisher's exact test).
      Our findings indicate that some children with HIV infection and gastrointestinal
      dysfunction may be infected with opportunistic pathogens despite negative
      analyses employing standard microbiological methods. Our study also indicates
      that HIV infected children can undergo intestinal infection with P. carinii
      despite the administration of standard immunoprophylactic regimens directed at
      the prevention of infection with this organism.

PMID- 8737390
TI  - Detection and molecular typing of Campylobacter jejuni in fecal samples by
      polymerase chain reaction.
AB  - In order to determine whether polymerase chain reaction (PCR) could be used to
      detect Campylobacter jejuni directly in stool samples, DNA from 66 frozen culture
      positive and negative fecal samples was purified by column chromatography. The
      flaA gene was amplified using primers directed against the conserved 5' and 3'
      regions and produced a 1.7 kb amplicon. Fifteen of 18 (83%) C. jejuni culture
      positive samples were detected by agarose gel electrophoresis and ethidium
      bromide staining. The test was negative in one sample containing C. coli. Twelve
      samples containing other enteric pathogens were negative as were 34 of 35 culture
      negative samples. Flagellin gene typing (see reference 14) of the flaA gene
      product from two stool samples in which the patients' stool isolate was also
      available showed the identical flagellin gene types suggesting that molecular
      typing of Campylobacter could potentially be performed on stool samples without
      the need for culture.

PMID- 8737391
TI  - Non isotopic automatable molecular procedures for the detection of enteroviruses.
AB  - Five microwell non isotopic hybridization assays, based on colorimetric
      immunoenzymatic reading, were developed and evaluated for the rapid and
      automatable detection of enteroviruses. Virus nucleic acids and/or capture probes
      were covalently bound to microtiter wells, and digoxigenin-11-dUTP was used as
      label for the detection of hybridized material. Among these procedures, a reverse
      transcriptase polymerase chain reaction (RT-PCR) hybridization assay was the most
      sensitive, enabling the detection of 10 MPNCU of poliovirus, and offering
      detection specificity for other enteroviruses, such as coxsackieviruses and
      echoviruses. The second most sensitive method was a complementary hybridization
      assay, simultaneously using three detection probes, one from the 5' end and two
      from the 3' end of poliovirus genome, offering a sensitivity for poliovirus
      detection of 5 x 10(3) MPNCU.

PMID- 8737392
TI  - Amplification of full-length HIV-2 envelope genes.
AB  - In contrast to HIV-1, no studies have been published on the genetic and
      functional analysis of the envelope gene of primary NSI isolates of HIV-2.
      However several studies on HIV-1 have shown that NSI strains are the most
      frequently transmitted strains and probably the most important strains in the
      pathogenesis of HIV infection. Furthermore, it has been shown that the genetic
      and biological characteristics of primary isolates of HIV-1 differ widely from
      those of T-cell-line adapted isolates. Two different polymerase chain reaction
      (PCR) methods, nested-polymerase chain reaction and overlapp-extension
      amplification, were used to amplify the envelope genes from a primary non
      syncytium-inducing HIV-2 isolate, HIV-2ALI, and from the T-cell line adapted
      syncytium-inducing isolate, HIV-2ROD. These methods could amplify the complete
      envelope gene from both viruses. Nested-polymerase chain reaction method was
      highly sensitive, enabling the amplification of one proviral copy of HIV-2ALI in
      10000 peripheral blood mononuclear cells. The use of the methods described herein
      may help to expand our knowledge on the genetic diversity of HIV-2 as well as on
      the structure and function of the envelope glycoproteins of primary HIV-2
      isolates.

PMID- 8737393
TI  - Fingerprinting sequence variation in ribosomal DNA of parasites by DGGE.
AB  - Although there is a tendency for rDNA genes within a species to maintain sequence
      homogeneity, there can be significant levels of variation among rDNA repeat
      sequences within populations or individuals of a species as a consequence of
      mutation mechanisms. To date, there have been no practical techniques available
      in molecular parasitology that allow the extent of sequence variation among the
      repeats (i.e., number of sequence types) to be displayed visually. In this
      report, we describe the use of the denaturing gradient gel electrophoresis (DGGE)
      technique for the rapid screening of parasite rDNA for sequence variation without
      the need for exhaustive cloning or DNA sequencing. The resolution of this
      variation by DGGE provides a diagnostic fingerprint for a species.

PMID- 8737394
TI  - Use of the polymerase chain reaction to specifically amplify integrated HPV-16
      DNA by virtue of its linkage to interspersed repetitive DNA.
AB  - A polymerase chain reaction (PCR) based technique that combines a virus specific
      primer and a human interspersed repetitive sequence (IRS) specific primer in
      order to detect integration of human papilloma virus type 16 (HPV-16) is
      described. Amplification of viral-host DNA junctions occurs when viral
      integration results in placement of the virus specific primer binding site near
      (less that 3-4 kb) the primer binding site within a repetitive sequence element.
      The method relies on enzyme labeled oligonucleotide probes to achieve rapid,
      specific, and nonradioisotopic detection of viral integration related PCR
      products since episomal forms of the viral DNA do not lead to exponential
      accumulation of hybridizable PCR products. The technique is demonstrated for
      human genomic DNA derived from clinical cervical swab specimens and archival
      paraffin embedded blocks. Viral integration was detected in 41% of the HPV-16
      positive samples (n = 34). In this positive subset, 64% were classified as
      invasive neoplasias, 29% CIN III and 7% CIN II. Analyzing the positive invasive
      neoplasias, 6 of 9 (66%) of the fingerprint results were obtained when an HPV
      primer was paired with an Alu primer. Interestingly, 100% of Alu primed
      fingerprint results obtained were derived from samples presenting invasive
      neoplasia (P < 0.025 by chi square).

PMID- 8737395
TI  - Polymerase chain reaction of bacterial genomes with single universal primer:
      application to distinguishing mycobacteria species.
AB  - The polymerase chain reaction with a single universal primer (UP-PCR) was applied
      to bacterial strains and mycobacteria isolates alongside conventional methods. A
      universal protocol of preparation of PCR samples from cultures representing
      Escherichia coli, Enterobacter aerogenes, Serratia marcescens, Staphylococcus
      aureus, Streptococcus pyogenes, Klebsiella pneumoniae, Mycobacterium
      tuberculosis, Mycobacterium bovis, and several non-tuberculous mycobacteria was
      found to be reproducible and efficient with these organisms. The bands of UP-PCR
      products observed in an agarose gel after electrophoresis were species-specific
      and provided an efficient means of distinguishing bacterial species. The
      applicability of this approach to mycobacteria identification was assessed by
      comparing the DNA bands obtained for different strains. Three reference strains
      and 22 clinical isolates of M. tuberculosis and M. bovis produced very similar
      DNA banding patterns. They comprised a triplet of prominent and several minor
      fragments within the 200-500 base pair (bp) size range and were the easiest to
      interpret. The DNA profiles of unrelated mycobacteria clearly differed from each
      other when subjected to electrophoretic analysis and correlated well with results
      of culture method. The method provides a real promise of its application in
      clinical studies as a simple assay for distinguishing between tubercle bacilli.

PMID- 8737396
TI  - 'Fingerprinting' of HLA-DQA by polymerase chain reaction and heteroduplex
      analysis.
AB  - We have developed a rapid, non-radioisotopic PCR fingerprinting technique for
      analysis of the HLA-Class II DQA gene second exon polymorphism, and have applied
      it to DNA samples from 210 healthy individuals. The technique is based on the
      formation of specific patterns (fingerprints) of homoduplexes or heteroduplexes
      between in vitro amplified DNA sequences. After electrophoresis on non-denaturing
      polyacrylamide gels and ethidium bromide fluorescence or silver staining,
      different HLA-DQA types give allele-specific banding patterns. HLA DQA typing is
      done by visual comparison between the sample's fingerprint patterns and
      appropriate controls. Similar fingerprints can be resolved by mixing the sample
      with a standard DNA in an amplified 'DNA crossmatch'. This application of PCR
      fingerprinting is useful to confirm the HLA-DQA serological typing and to improve
      the molecular characterization of this polymorphic region.

PMID- 8737397
TI  - A quantitative polymerase chain reaction (PCR) assay completely discriminates
      between Duchenne and Becker muscular dystrophy deletion carriers and normal
      females.
AB  - Duchenne/Becker muscular dystrophy (DMD/BMD) is a severe X-linked myopathy. In
      65% of the patients, the mutations responsible for the disease are macrodeletions
      in the dystrophin-encoding gene that can be identified with multiplex polymerase
      chain reaction (PCR) technology. We developed a method for quantitative PCR
      analysis of deletion carriers involving the use of phosphorimager-based scanning
      of radioactive-labelled PCR products. We calculated the ratios between the areas
      of two peaks, one corresponding to the deleted segments to be analysed and the
      other taken as a reference. In carriers, these ratios (R value) were always about
      half those obtained in normal females. The final diagnostic result, the
      diagnostic index (DI), is the ratio of the R values between the propositus and a
      normal subject. We also assessed the variability of each step of the procedure
      and the overall variability of the DI value, thus obtaining cut-off values that
      completely discriminated BMD/DMD deletion carriers from normal females. We were
      also able to classify, as either 'carrier' or 'normal', several females whose
      status was not identified with linkage analysis.

PMID- 8737398
TI  - Non-radioisotopic detection of human xenogeneic DNA in a mouse transplantation
      model.
AB  - Xenogeneic mouse models are widely used for the study of human tumor growth and
      metastasis. To date, few methods have been developed to track and quantitate the
      colonization of mouse organs with transplanted human cells. In this paper, a
      family of nonradioisotopic DNA oligonucleotide probes that are complementary to
      sequences within the human Alu element are characterized. These probes can be
      used in Southern hybridization reactions to quantitate the colonization of mouse
      organs with human derived cells. One oligonucleotide probe, the Alu-C probe, was
      identified as the most sensitive and specific in the family of probes synthesized
      for the distinction of human genomic DNA in a mouse genomic DNA background. The
      Alu-C probe can identify 0.05 ng human diploid DNA in a mouse background of 500
      ng of genomic DNA. This represents 7.5 human diploid cells admixed with 75,000
      mouse diploid cells. The Alu-C probe can therefore be employed to assess human
      colonization in xenograft models for a variety of human tumors and non-neoplastic
      tissues.

PMID- 8737399
TI  - A practical strategy for detection of major chromosome aneuploidies using ratio
      mixing fluorescence in situ hybridization.
AB  - We describe the use of ratio-mixing FISH to visualize simultaneously probe sets
      specific for chromosomes 13, 18 and 21 as well as both sex chromosomes in
      uncultured lymphocytes and amniocytes. This method has the advantage of a smaller
      sample requirement than uni-colour FISH and potential for analysis of a larger
      number of chromosome aneuploidies using a minimum number of different probe
      haptenization and detection systems. An unselected series of uncultured
      lymphocytes and amniocytes was used to investigate the reliability of ratio
      mixing FISH for diagnostic applications. The results indicate that the five
      colour ratio-mixing FISH is a reliable technique and can be used for simultaneous
      detection of major aneuploidies. However, as a diagnostic approach, the strategy
      of using a three-colour ratio-mixing FISH and a dual colour to detect the five
      clinically important aneuploidies on two slides from the same sample, appears to
      be simpler and more practical.

PMID- 8737400
TI  - Characterization of four microsatellites in an Italian population and their
      application to paternity testing.
AB  - Microsatellites have recently been used for linkage analysis of genetic diseases
      and for DNA fingerprinting in forensic medicine. In the present study the
      heterozygosity, PIC values and allele distributions of four microsatellites,
      D8S85, D8S88, D5S346 and D7S460, in an Italian population have been investigated.
      After amplification with primers specific for each locus, alleles were separated
      and detected by denaturing gel electrophoresis and ethidium bromide staining.
      High heterozygosity and PIC values were observed for all microsatellites in
      accordance with data in other Caucasian populations. However, different allele
      distributions for D8S85, D8S88 and D5S346, due to the presence of additional
      bands or to different frequencies, were found. D7S460, which has never been fully
      characterized before, appeared to have five alleles in the range 172 to 188 bp.
      When used for paternity testing, all microsatellites gave results which were
      consistent with those obtained with established markers, including apo B 3'HVR,
      D1S80 and COL2A1. This indicates that D8S85, D8S88, D5S346 and D7S460 may be
      useful as additional informative markers or for solving discrepancies in selected
      cases.

PMID- 8737401
TI  - Progressive cortical synchronization of ponto-geniculo-occipital potentials
      during rapid eye movement sleep.
AB  - Phasic events, termed ponto-geniculo-occipital potentials, appear in the
      brainstem, thalamus and cerebral cortex during rapid eye movement sleep. In the
      cat, the species of choice for ponto-geniculo-occipital studies, these field
      potentials are usually recorded from the lateral geniculate thalamic nucleus and
      visual cortex. However, the fact that brainstem cholinergic neurons play a
      crucial role in the transfer of ponto-geniculo-occipital potentials to the
      thalamus, coupled with the evidence that mesopontine tegmental neurons project to
      virtually all thalamic nuclei, together explain why ponto-geniculo-occipital
      potentials are recorded over widespread territories, beyond the visual
      thalamocortical system. Here we demonstrate, by means of multi-site unit and
      field potential recordings from sensory, motor and association cortical areas in
      behaving cats, that: (i) ponto-geniculo-occipital potentials appear synchronously
      over the neocortex; and (ii) that their cortical synchronization develops
      progressively from the period preceding rapid eye movement sleep by 30-90 s (pre
      rapid eye movement), to reach the highest degree of intracortical coherence
      during later epochs of rapid eye movement sleep. We propose that the widespread
      coherence of cortical ponto-geniculo-occipital potentials underlies the
      synchronization of fast oscillations (30-40 Hz) during rapid eye movement sleep
      over many, functionally distinct cortical territories implicated in dreaming, as
      brainstem-induced ponto-geniculo-occipital-like potentials are consistently
      followed by such fast oscillations.

PMID- 8737402
TI  - Ultrastructural localization of the plasmalemmal calcium pump in cerebellar
      neurons.
AB  - In a previous study, fluorescence labeling of a plasmalemmal ATPase protein with
      the 5F10 monoclonal antibody revealed prominent antigen in the cerebellar
      molecular layer surrounding the somata and dendrites of Purkinje cells. In the
      present study, this antibody labeled with silver enhanced nano-sized gold
      particles on semithin plastic sections revealed a clearly demarcated plasma
      membrane outlining the somata and entire dendritic arbors of Purkinje cells
      including their spines. Ultrastructural analysis of horseradish peroxidase
      preparations showed reaction product along the plasmalemma and extending on to
      the sub-plasmalemmal endoplasmic reticulum. In the granular layer, somata of
      granule cells were reactive, as were their dendritic extensions into glomeruli
      where reactive claws surrounded voids formed by mossy fiber rosettes. Somata and
      dendrites of cerebellar nuclear cells also had reactive zones that were limited
      to the plasma membrane and a narrow zone of the sub-plasmalemmal endoplasmic
      reticulum. Comparative labeling of this protein and P channel protein revealed
      similar plasmalemmal locations. This study shows that a specific calcium ATPase
      pump protein is located on the plasmalemma of certain types of cerebellar
      neurons. The ultrastructural distribution of calcium pump and P channel
      antibodies occurred in punctate sites along the plasma membrane of dendrites and
      spines of Purkinje cells. The close association between P-type calcium channels
      and the plasma membrane calcium pump is consistent with rapid extrusion of
      intracellular calcium from neurons endowed with large numbers of voltage-gated
      calcium channels.

PMID- 8737403
TI  - Metabolic activity pattern in the motor and somatosensory cortex of monkeys
      performing a visually guided reaching task with one forelimb.
AB  - The [14C]deoxyglucose method was used to map the metabolic activity in the
      primary somatosensory and motor cortex in monkeys (Macaca nemestrina) performing
      a unimanual task. The task required visually guided reaching and target holding
      at a rate of about 10 movements per min. The entire dorsoventral extent of the
      cortical region lying between the posterior crown of the arcuate and the anterior
      crown of the intraparietal sulci was reconstructed on the sagittal plane, from
      horizontal sections aligned on the fundus of the central sulcus. The metabolic
      mapping of the control monkey demonstrated homogeneous activity all around the
      central sulcus, bilaterally. The mapped activity in the performing monkeys
      displayed two different patterns. The first pattern, contralateral to the moving
      forelimb, was characterized by several discrete regions of increased metabolic
      activity, which were symmetrically distributed in a mirror image fashion around
      the fundus of the central sulcus. These activated regions correspond to the lower
      body, forelimb, and mouth areas of representation of body parts in previously
      reported maps in primary motor and somatosensory cortical areas. The second
      activity pattern ipsilateral to the moving forelimb, displayed activated
      somatosensory and motor regions corresponding only to the lower body, and mouth
      representations. Our study provides a continuous, high resolution map of activity
      pattern in the entire primary motor and somatosensory cortices, which
      demonstrates that the reaching forelimb is controlled by a discrete subregion in
      the contralateral somatosensorimotor cortex, whereas other subregions of body
      representation are actively involved, bilaterally, during the performance of a
      relatively simple motor behaviour.

PMID- 8737404
TI  - Preincubation with protein synthesis inhibitors protects cortical neurons against
      oxygen-glucose deprivation-induced death.
AB  - Twenty-four hour exposure to cycloheximide produced a concentration-dependent
      reduction in protein synthesis in mouse cortical cell cultures. Unexpectedly, a
      24 h pretreatment with cycloheximide exposure also reduced neuronal vulnerability
      to subsequent oxygen-glucose deprivation-induced injury, measured both acutely
      (cell swelling) or after one day (cell lysis). This neuroprotective effect was
      attenuated if the period of cycloheximide pretreatment was shortened to 8 h, and
      lost if the pretreatment was shortened to 1 h. A comparable neuroprotective
      effect was also induced by 24 h pretreatment with another protein synthesis
      inhibitor, emetine. The neuroprotection induced by pretreatment with
      cycloheximide or emetine was probably not attributable to reduction of apoptosis:
      (i) neuronal death under these conditions occurs by N-methyl-D-aspartate receptor
      mediated excitotoxic necrosis, not apoptosis; (ii) the same cycloheximide
      pretreatment did not block staurosporine-induced apoptosis. Also unlikely as an
      explanation is reduction in postsynaptic vulnerability to excitotoxicity, as
      death induced by exogenous addition of N-methyl-D-aspartate, kainate, or alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionate was little affected by
      cycloheximide pretreatment. Rather, the protective effect of cycloheximide
      pretreatment was probably explained, at least in part, by marked reduction in the
      glutamate release induced by oxygen-glucose deprivation.

PMID- 8737405
TI  - Attenuated hippocampal damage after global cerebral ischemia in mice mutant in
      neuronal nitric oxide synthase.
AB  - To address the importance of nitric oxide or its reaction products as mediators
      of neurotoxicity in brain, tissue injury was assessed after transient global
      ischemia in mice rendered mutant in the gene for neuronal nitric oxide synthase.
      Halothane-anesthetized wild type and mutant mice were subjected to temporary
      occlusion of the basilar plus both carotid arteries for 5 or 10 min followed by
      three days of reperfusion. Hippocampal injury, assessed both by qualitative
      grading and by cell counting in the CA1 subregion, was significantly less in the
      mutant mice group after 5 or 10 min of ischemia. Mutant mice exhibited a lower
      mortality (P < 0.01), less weight loss, more normal grooming and spontaneous
      motor activity and better grasping in the 10 min group. There were no obvious
      differences in cerebrovascular anatomy or hemodynamics between wild type and
      mutant mice. The data suggest that a deficiency of neuronal nitric oxide synthase
      confers increased resistance to transient global cerebral ischemia, and support
      the suggestion that selective neuronal nitric oxide synthase inhibitors might
      reduce tissue injury associated with global cerebral ischemia.

PMID- 8737406
TI  - Nitric oxide synthase and neuronal vulnerability in Parkinson's disease.
AB  - Parkinson's disease is characterized by a loss of dopaminergic neurons in the
      mesencephalon. Although the mechanism of this neuronal loss is still unknown,
      oxidative stress is very likely involved in the cascade of events leading to
      nerve cell death. Since nitric oxide could be involved in the production of free
      radicals, we analysed, using immunohistochemistry and histochemistry, the
      production systems of nitric oxide in the mesencephalon of four patients with
      idiopathic Parkinson's disease and three matched control subjects. Using specific
      antibodies directed against the inducible isoform of nitric oxide synthase (the
      enzyme involved in the synthesis of nitric oxide), we found evidence to suggest
      that this isoform was present solely in glial cells displaying the morphological
      characteristics of activated macrophages. Immunohistochemical analysis performed
      with antibodies against the neuronal isoform of nitric oxide synthase, however,
      revealed perikarya and processes of neurons but no glial cell staining. The
      number of nitric oxide synthase-containing cells was investigated by
      histoenzymology, using the NADPH-diaphorase activity of nitric oxide synthase.
      Histochemistry revealed (i) a significant increase in NADPH-diaphorase-positive
      glial cell density in the dopaminergic cell groups characterized by neuronal loss
      in Parkinson's disease and (ii) a neuronal loss in Parkinson's disease that was
      two-fold greater for pigmented NADPH-diaphorase-negative neurons than for
      pigmented NADPH-diaphorase-positive neurons. These data suggest a potentially
      deleterious role of glial cells producing excessive levels of nitric oxide in
      Parkinson's disease, which may be neurotoxic for a subpopulation of dopaminergic
      neurons, especially those not expressing NADPH-diaphorase activity. However, it
      cannot be excluded that the presence of glial cells expressing nitric oxide
      synthase in the substantia nigra of patients with Parkinson's disease represents
      a consequence of dopaminergic neuronal loss.

PMID- 8737407
TI  - Differential distribution of nicotinamide adenine dinucleotide phosphate
      diaphorase and neural nitric oxide synthase in the rat choroid plexus. A
      histochemical and immunocytochemical study.
AB  - This study used NADPH diaphorase (NADPHd) histochemistry and neuronal nitric
      oxide synthase immunocytochemistry to examine the localization of nitric oxide
      synthase in the choroid plexus of the lateral ventricles and the fourth ventricle
      of rat brain. That the NADPHd reaction product in choroid plexus was specific to
      nitric oxide synthase was evaluated: (i) by comparison to immunocytochemical
      labelling for nitric oxide synthase; and (ii) by comparing NADPHd histochemical
      staining in choroid plexus and brain (rich in nitric oxide synthase-positive and
      NADPHd-positive neurons) in the presence or absence of iodonium diphenyl or
      dichlorophenolindophenol, two potent albeit non-selective inhibitors of nitric
      oxide synthase activity. In brain, NADPHd histochemistry homogeneously stained
      neuronal cell bodies, axons and dendrites, while it produced particulate
      cytoplasmic staining of all epithelial cells in the choroid plexuses of the
      lateral and fourth ventricles. Within the choroid plexus of the lateral
      ventricles, NADPHd-positive nerve fibres were also observed around blood vessels
      and coursing among the epithelial cells. The distribution of immunoreactivity for
      nitric oxide synthase in brain and in nerve fibres in the choroid plexuses of the
      lateral ventricles resembled the distribution of histochemical labelling for
      NADPHd. Choroid plexus epithelial cells were, however, devoid of nitric oxide
      synthase immunoreactivity. Consistent with this, iodonium diphenyl and
      dichlorophenolindophenol (0.1 mM) inhibited NADPHd histochemical staining in
      brain neurons and in choroid plexus nerve fibres, but not in choroid plexus
      epithelial cells. These results demonstrate that the choroid plexus of the
      lateral ventricles in rat brain is innervated by nitric oxide synthase-positive
      nerve fibres. These nitric oxide synthase-positive nerve fibres may have an
      important role in the regulation of cerebrospinal fluid balance. Although choroid
      plexus epithelial cells contain an enzyme with NADPHd activity, this enzyme is
      not nitric oxide synthase.

PMID- 8737408
TI  - Chromogranin A triggers a phenotypic transformation and the generation of nitric
      oxide in brain microglial cells.
AB  - Chromogranin A is an ubiquitous 48,000 mol. wt secretory protein stored and
      released from many neuroendocrine cells and neurons. In human brain, chromogranin
      A is a common feature of regions that are known to be affected by various
      neurodegenerative pathologies such as Alzheimer's, Parkinson's and Pick's
      diseases. Brain degenerative areas are generally infiltrated by activated
      microglial cells, the resident macrophage cell population within the central
      nervous system. Here, we report that both recombinant human chromogranin A and
      chromogranin A purified from bovine chromaffin granules trigger drastic
      morphological changes in rat microglial cells maintained in culture. Microglial
      cells exposed to chromogranin A adopted a flattened amoeboid shape and, this
      change was associated with an accumulation of actin in the subplasmalemmal
      region, as observed by immunocytochemistry and confocal laser microscopy. In
      single microglial cells loaded with indo-1, chromogranin A elicited a rapid and
      transient increase in [Ca2+]i which preceded the reorganization of actin
      cytoskeleton. The activity of nitric oxide synthase was estimated by measuring
      the accumulation of nitrite in the culture medium. Both recombinant human
      chromogranin A and bovine chromogranin A triggered an important accumulation of
      nitrite comparable to that induced by lipopolysaccharide, a well-known activator
      of microglia. The effect of chromogranin A was dose dependent, inhibited by N
      omega-nitro-L-arginine methyl ester, a competitive inhibitor of nitric oxide
      synthase, and by cycloheximide, an inhibitor of protein synthesis. These findings
      suggest that chromogranin A induces an activated phenotype of microglia, and thus
      may have a role in the pathogenesis of neuronal degeneration in the brain.

PMID- 8737409
TI  - Effect of ascorbic acid on hyperoxic rat astrocytes.
AB  - The effect of ascorbic acid on cell size and ascorbic acid transport was studied
      in hyperoxic astrocytes. Subcultured rat astrocytes plated on poly-L-lysine
      coated coverslips or on plastic dishes were exposed to serum-free culture medium
      and 20% or 42% ambient oxygen for 48 h. Vehicle (homocysteine) or L-ascorbic acid
      was added to the medium at 0 and 24 h. Cell size and relative optical density of
      glial fibrillary acidic protein-positive astrocytes were measured by a
      computerized imaging system. Cells on the dishes were used for ascorbic acid
      transport studies. Hyperoxia significantly increased the cell size of astrocytes,
      and this effect was inhibited by ascorbic acid. The rate of L-[14C]ascorbic acid
      Na(+)-dependent uptake was also inhibited by hyperoxia in vehicle-treated
      cultures but not in ascorbic acid-supplemented cultures. These results indicate
      that the presence of ascorbic acid during the hyperoxic episode can prevent
      astrocytic cell swelling and preserve membrane transport function.

PMID- 8737410
TI  - Epileptiform activity induced by pilocarpine in the rat hippocampal-entorhinal
      slice preparation.
AB  - An in vitro slice preparation of combined hippocampus and entorhinal cortex from
      adult rats was used to study the modalities of generation and propagation, as
      well as the pharmacological properties of the epileptiform activity induced by
      the muscarinic agonist pilocarpine (10 microM). Simultaneous field potentials
      recordings were made from the medial entorhinal cortex and from the dentate
      gyrus, CA3 and CA1 subfields. Pilocarpine application induced two types of
      interictal epileptiform discharges. The first occurred in the entorhinal cortex
      and consisted of bursts of population spikes lasting 408 +/- 135 ms (n = 20
      slices) and repeating at a rate of 0.26 +/- 0.07 Hz (n = 20); this interictal
      activity propagated to the hippocampus via the perforant path. The second type
      was only observed in CA3 and CA1 subfields, had shorter duration (82 +/- 16 ms; n
      = 20) and occurred at a higher rate (1.42 +/- 0.7 Hz; n = 20) than the first
      type. Ictal epileptiform discharges (duration: 11.5 +/- 4.1 s; rate: 0.002 +/-
      0.0009 Hz; n = 10) were also seen in the entorhinal cortex, from where they
      propagated to the dentate, CA3 and CA1 via the hippocampal trisynaptic loop as
      revealed by latency analysis and lesion experiments. Ictal and interictal
      discharges of entorhinal origin disappeared in the hippocampal sectors, but
      continued to occur in the entorhinal cortex following a cut of the perforant path
      (n = 5). Fast interictal discharges observed solely in the hippocampus originated
      in CA3, since sectioning the Schaffer collaterals made them disappear in CA1 (n =
      7). All types of epileptiform activity disappeared during application of the non
      N-methyl-D-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione
      (10 microM; n = 7). By contrast, the N-methyl-D-aspartate receptor antagonist 3
      3(2-carboxy-piperazine-4-yl) propyl-1-phosphonate (10 microM) abolished ictal
      discharges in the entorhinal cortex and reduced the duration of the interictal
      events recorded in this area (n = 7). Interictal discharges originating from CA3
      continued to occur at a higher rate than in control during application of this N
      methyl-D-aspartate receptor antagonist. Our study confirms that the combined
      hippocampal-entorhinal slice preparation represents a suitable model for
      understanding the modalities of origin and propagation of epileptiform activity
      within the limbic system. In this in vitro preparation, the entorhinal cortex is
      the site of origin for ictal discharges. Moreover, the different types of
      epileptiform activity induced by this muscarinic agonist have specific, structure
      dependent pharmacological profiles. These results are discussed in relation to
      those obtained in vivo.

PMID- 8737411
TI  - Regeneration of the GABAergic septohippocampal projection in vitro.
AB  - The formation of the GABAergic septohippocampal projection was studied in vitro.
      Slice cultures of the septal complex from young postnatal rats were prepared and
      co-cultivated with hippocampal slices for up to four weeks. Then, the
      anterogradely transported tracer Phaseolus vulgaris leucoagglutinin was injected
      into the septal culture and the labeled fibers were traced into the hippocampal
      culture. Some fibers were identified as originating from GABAergic septal cells
      by double-labeling with an antiserum against GABA using the postembedding
      immunogold procedure. Our results showed that double-labeled terminals of
      GABAergic septohippocampal neurons established symmetric synapses exclusively
      with GABA-positive dendrites in one out of five co-cultures, but also contacted
      numerous GABA-negative structures in the remaining four co-cultures. These
      findings, together with light microscopic data from sections double-stained for
      Phaseolus and parvalbumin, indicate that the high target selectivity of the
      GABAergic septohippocampal pathway for GABAergic interneurons in vivo is lost in
      most cases, at least under the present in vitro conditions. It is hypothesized
      that this may be due to an immaturity of the connection, the lack of axon-guiding
      factors or an expansion of the septohippocampal GABAergic fibers in the absence
      of many extrinsic afferents, including GABAergic fibers. The simultaneous
      occurrence of anterogradely labeled, but GABA-negative, septohippocampal
      terminals in the hippocampal target culture also suggests that the
      septohippocampal cholinergic projection developed in vitro, as was shown before
      in other studies. Since most septohippocampal neurons have to be axotomized for
      culture preparation, the present results indicate that GABAergic septohippocampal
      neurons from young postnatal rats survive axotomy and are capable of regenerating
      a septohippocampal projection, including the formation of characteristic
      GABAergic synapses on co-cultured hippocampal neurons. However, the
      characteristic target selectivity is rarely preserved.

PMID- 8737412
TI  - Differential effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      and N-methyl-D-aspartate receptor antagonists applied to the basal forebrain on
      cortical acetylcholine release and electroencephalogram desynchronization.
AB  - It is known that glutamatergic tracts activated from the pedunculopontine
      tegmentum represent a major input to the nucleus basalis magnocellularis. To
      establish the role of different ionotropic glutamate receptors in synaptic
      transmission in the basal forebrain, the pedunculopontine tegmentum was
      stimulated in urethane-anesthetized rats and the resulting increases in cortical
      acetylcholine release and desynchronization of the electroencephalogram were
      monitored. R(-)-3-(2-carboxypiperazine-4-yl)-propyl-I-phosphonic acid (CPP), an
      antagonist at N-methyl-D-aspartate-type glutamate receptors, and 6, 7
      dinitroquinoxaline-2, 3-dione (DNQX), an antagonist at alpha-amino-3-hydroxy-5
      methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors, were delivered
      through a microdialysis probe placed in the basal forebrain. The N-methyl-D
      aspartate antagonist preferentially inhibited cortical acetylcholine release,
      while the AMPA antagonist was more powerful in reducing desynchronization. A
      combination of both N-methyl-D-aspartate and AMPA antagonists abolished the
      increase in cortical acetylcholine release without reducing desynchronization.
      The dissociation between increased cortical acetylcholine release and
      electroencephalogram desynchronization suggests that the activity of corticopetal
      basal forebrain cholinergic neurons is neither necessary nor sufficient to
      produce electroencephalogram desynchronization. Rather, the nucleus basalis can
      probably affect the electroencephalogram by its projections to the thalamus. The
      reversal of the inhibitory effect of DNQX on the electroencephalogram by CPP may
      be due to the blockade of N-methyl-D-aspartate receptors on the GABAergic
      projection from the basal forebrain to the thalamus.

PMID- 8737413
TI  - Age-related changes in diurnal acetylcholine release in the prefrontal cortex of
      male rats as measured by microdialysis.
AB  - Extracellular levels of acetylcholine in the prefrontal cortex were measured
      using the micro-dialysis method in freely moving young (three to four months old)
      and old (23 to 24 months old) male rats over a period of 24 h to examine the
      effect of aging on prefrontal acetylcholine release. Prefrontal acetylcholine
      release during a 24 h period exhibited a diurnal variation with higher levels
      during the dark cycle than during the light cycle in young rats but not in old
      rats. In addition, prefrontal acetylcholine release was closely associated with
      spontaneous activity in young rats but not in old rats. The present study
      suggests that aging reduces diurnal changes in the prefrontal acetylcholine
      release and that there is a cross-correlation between the prefrontal
      acetylcholine release and spontaneous locomotor activity in male rats.

PMID- 8737414
TI  - Glutamate decarboxylase immunoreactivity in corticocortical projecting neurons of
      rat somatic sensory cortex.
AB  - Combined retrograde tracing and immunocytochemical experiments were carried out
      on rats to ascertain whether corticocortical projecting neurons in the somatic
      sensory areas are immunoreactive to an antiserum against glutamate decarboxylase.
      Injections of a retrograde tracer (colloidal gold-labelled wheat germ agglutinin
      conjugated to enzymatically inactive horseradish peroxidase) in the first somatic
      sensory area labelled neurons in the injected area, in the second somatic sensory
      area, and in the parietoventral area of the ipsilateral hemisphere. The
      topographical and laminar distribution of these retrogradely-labelled
      corticocortical neurons in the first and second somatic sensory areas and in the
      parietoventral area was in line with a previous description (Fabri M. and Burton
      H. (1991b) J. comp. Neurol. 311, 405-424). In sections processed for the
      simultaneous visualization of the retrograde tracer and glutamate decarboxylase
      immunoreactivity, a number of neurons were double-labelled. Double-labelled
      neurons were most numerous in the first somatic sensory cortex, where they
      accounted for 5% of all retrogradely-labelled neurons. Outside this region,
      double-labelled cells were observed in the second somatic sensory cortex and in
      the parietoventral cortex, where they amounted respectively to 2.8% and 2.3% of
      all corticocortical neurons labelled in these two areas. Glutamate decarboxylase
      immunopositive corticocortical neurons were mainly concentrated in the
      infragranular layers (73.8% of all double-labelled neurons in the first somatic
      sensory area, 81.7% in the second somatic sensory area, and 76.5% in the
      parietoventral area). The results indicate the presence of a small but
      significant contingent of GABAergic inhibitory neurons in the associative
      connections of the somatic sensory areas.

PMID- 8737415
TI  - Electron microscopic serial-sectioning/reconstruction study of parvalbumin
      containing neurons in the external plexiform layer of the rat olfactory bulb.
AB  - Neurons containing a calcium-binding protein parvalbumin in the external
      plexiform layer of the rat olfactory bulb were identified light microscopically
      with the pre-embedding immunocytochemistry and were subsequently analysed with
      the electron microscopic serial-sectioning and three-dimensional reconstructions.
      In the present study we chose several different types of parvalbumin
      immunoreactive neurons identified light microscopically as Van Gehuchten cell
      type, superficial short-axon cell type and multipolar cell type. Parvalbumin
      immunoreactive somata were similar to one another in their ultrastructural
      characteristics, showing nuclear indentations, moderately developed Golgi
      apparatus and abundant mitochondria; these structural features appeared to
      resemble those of the short axon cells around the glomeruli and in the granule
      cell layer reported in previous electron microscopic studies. All neurons
      analysed in the present study made symmetrical synapses on to dendrites and
      somata of presumed mitral/tufted cells and received asymmetrical synapses from
      them, and occasionally formed reciprocal synapses with them. On the parvalbumin
      immunoreactive processes, the asymmetrical synapses nearly equalled the
      symmetrical ones in number and about 30-50% of them were identified as reciprocal
      pairs. In contrast, no presynaptic sites were observed on parvalbumin
      immunoreactive somata, and thick portions (more than approximately 2 microns in
      diameter) of the proximal dendrites, where they were occasionally postsynaptic in
      some asymmetrical and symmetrical synapses from parvalbumin-immunonegative
      profiles. Characteristically, parvalbumin-immunoreactive process frequently make
      direct contacts with one another; processes regarded light microscopically as
      arising from a soma or a dendrite or parvalbumin-immunoreactive neurons were
      sometimes revealed to be separate but directly contacting processes with electron
      microscopic examinations. Although puncta adherentia were occasionally observed
      between these contact sites, so far neither gap junctions nor chemical synapses
      were observed. Until now, it has been believed that in the external plexiform
      layer only granule cells form reciprocal synapses with mitral/tufted cells.
      However, the present study clearly demonstrates that interneurons different from
      granule cells, namely GABAergic neurons containing a calcium-binding protein
      parvalbumin, also make reciprocal synapses with mitral/tufted cells in the
      external plexiform layer. Therefore, neuronal processes making reciprocal
      synapses with mitral/tufted cells in the external plexiform layer cannot be
      determined a priori as granule cell processes.

PMID- 8737416
TI  - Steroid metabolizing enzymes in pluripotential progenitor central nervous system
      cells: effect of differentiation and maturation.
AB  - A novel in vitro system which allows extensive culturing of multipotential stem
      cells from mouse brain has made it possible to test whether enzymes that
      metabolize androgens and progestagens are present in undifferentiated central
      nervous system progenitor cells. Embryonic day 14 striatal cells were grown in
      the presence of either 20 ng/ml of epidermal growth factor (which prevents cell
      differentiation), or 2% fetal bovine serum (facilitating differentiation).
      Differentiation was complete by 35 days in vitro when the cell population
      comprised 86 +/- 2.0% astrocytes, 6 +/- 0.7% neurons 1.6 +/- 0.5%
      oligodendrocytes and 6.4 +/- 0.5% undifferentiated cells. No changes in the
      proportions of cell type were observed thereafter (38 and 45 days in vitro). 5
      alpha-Reductive conversion (by 5 alpha-reductase) of testosterone and
      progesterone into dihydrotestosterone and dihydroprogesterone, and subsequent 3
      alpha hydroxylation (by 3 alpha-hydroxysteroid dehydrogenase) to 3 alpha-diol and
      tetrahydroprogesterone were assayed in the cultures at 35, 38 and 45 days in
      vitro. Undifferentiated epidermal growth factor-treated cells (controls) formed
      about 10 times more dihydroprogesterone than dihydrotestosterone. Conversions of
      dihydrotestosterone and dihydroprogesterone, respectively, into 3 alpha-diol and
      tetrahydroprogesterone were very similar. In the fetal bovine serum-treated
      differentiating cells, 5 alpha-reductase converting progesterone increased at 38
      days in vitro, and remained similarly elevated at 42 days in vitro (4 times).
      However, the conversion of testosterone into dihydrotestosterone remained at
      control levels up to 42 days in vitro when an increase was observed. 3 alpha
      Hydroxysteroid dehydrogenase activity converting dihydroprogesterone but not
      dihydrotestosterone was increased at 38 and 42 days in vitro. These results show
      that undifferentiated central nervous system cells possess androgen and
      progestagen metabolizing enzymes which are strongly influenced by the cellular
      differentiation/maturation process.

PMID- 8737417
TI  - Early gestational mesencephalon grafts, but not later gestational mesencephalon,
      cerebellum or sham grafts, increase dopamine in caudate nucleus of MPTP-treated
      monkeys.
AB  - The mechanism of the behavioral improvement observed in parkinsonian primates
      that receive intrastriatal transplants of fetal dopamine neurons has not been
      firmly established. Dopamine production by grafted neurons may be the basis of
      the behavioral recovery. Alternatively, stimulation of the host dopamine system
      by the transplant procedure itself may be central to the outcome. The present
      study examined whether dopamine concentration was raised in the caudate nucleus
      of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primate
      following grafting, and if so, whether the elevation was dependent on either (i)
      the introduction of the implantation cannula (sham), (ii) the brain region that
      was grafted, or (iii) the gestational age of fetal tissue that was grafted.
      Transplantation of early gestational age fetal ventral mesencephalon (embryonic
      days 40-50) was associated with significant elevation of caudate nucleus dopamine
      concentration to a mean of approximately 20% of control values in the vicinity
      (within 2 mm) of the graft, compared with more distant sites in the caudate
      nucleus. With early gestational age fetal ventral mesencephalon, the ratio of
      homovanillic acid/dopamine concentration near the graft site was normalized
      compared to the elevated value found in the caudate nucleus distant from the
      graft site. Grafts of later stage fetal ventral mesencephalon, or fetal
      cerebellum, or sham implantation did not increase dopamine concentration or lower
      homovanillic acid/dopamine ratio near the graft site. Biochemical and
      histochemical evidence suggests that host dopamine neurons terminating in the
      nucleus accumbens are not the source of the changes. Numerous tyrosine
      hydroxylase-positive neurons at the graft site were only observed in the MPTP
      treated monkeys that received grafts of early gestational age fetal ventral
      mesencephalon. These data lend strong support to the hypothesis that dopamine
      derived from grafted dopamine neurons is the major basis for behavioral recovery
      observed following intrastriatal transplantation in our MPTP-treated monkeys.

PMID- 8737418
TI  - A topographic re-evaluation of the nigrostriatal projections to the caudate
      nucleus in the cat with multiple retrograde tracers.
AB  - The anatomical organization of the cat nigrostriatal projections to the caudate
      nucleus was studied by retrograde tracer techniques. Horseradish peroxidase
      conjugated with wheat germ agglutinin and fluorescent retrograde tracers such as
      Fast Blue and Diamidino Yellow were injected concomitantly in different regions
      of the caudate nucleus. The distribution of single and double retrogradely
      labeled neurons was analysed in the substantia nigra pars compacta, substantia
      nigra pars lateralis, retrorubral area and adjacent ventral tegmental area.
      Adjacent sections processed for acetylcholinesterase were used as histochemical
      markers for the densocellular zone of the substantia nigra. The main findings of
      this study are: (1) The rostral caudate nucleus receives projections mainly from
      the caudal substantia nigra while the caudal caudate nucleus receives projections
      from all rostrocaudal levels of the substantia nigra. (2) The substantia nigra
      pars lateralis projects very specifically to the caudal caudate nucleus. (3) The
      ventral retrorubral area close to the medial lemniscus projects to all
      rostrocaudal levels of the caudate nucleus. (4) The rostral caudate nucleus
      receives projections mainly from the medial substantia nigra while more caudal
      sectors of the caudate nucleus receive projections from the medial and lateral
      substantia nigra. (5) A dorsoventral inversion of nigrostriatal projections from
      the medial substantia nigra pars compacta and the adjacent ventral tegmental area
      to the caudate nucleus was established. In contrast, we found zones within the
      retrorubral area projecting both to the dorsal and ventral caudate nucleus. (6)
      Distant injections of two different fluorescent tracers regarding both the
      dorsoventral and the rostrocaudal coordinates, yielded double-labeled neurons
      that were mainly located in the medial and caudal portions of the substantia
      nigra and in the ventral retrorubral area. However, the number of double-labeled
      neurons was higher after separated injections in the dorsoventral axis,
      suggesting that the collateralization to the caudate nucleus occurs mainly in the
      dorsoventral plane. (7) A clustering organization of nigrostriatal cells
      projecting to the caudate nucleus was detected mainly in the intermediate
      rostrocaudal part of the substantia nigra pars compacta and in the retrorubral
      area. The results of this comprehensive study on the cat nigrostriatal pathway to
      the caudate nucleus show novel findings on the anatomical organization of the
      nigrostriatal projections which might help the understanding of the complex
      architecture of nigral neurons projecting to the caudate nucleus in carnivores.

PMID- 8737419
TI  - Increased expression of type 1 insulin-like growth factor receptor messenger RNA
      in rat hippocampal formation is associated with aging and behavioral impairment.
AB  - Insulin-like growth factor messenger RNAs are expressed in adult rat brain.
      However, little is known about the effects of aging on the expression of the
      insulin-like growth factors, their receptors, and their binding proteins in
      different regions of rat brain. The goal of the current study was to assess
      whether there is altered expression of the insulin-like growth factor system
      during normal aging in the hippocampal formation, a region particularly
      vulnerable to the aging process. A spatial learning task in the Morris water maze
      was used to assess the cognitive status of young (7-8-month-old) and aged (28-29
      month-old) male Long-Evans rats. Sites of expression and abundance of insulin
      like growth factor-I, type 1 insulin-like growth factor receptor, and insulin
      like growth factor binding protein-4 messenger RNAs were then examined by in situ
      hybridization histochemistry and solution or northern blot hybridization assays.
      In situ hybridization histochemistry revealed no qualitative differences in the
      regional distribution of insulin-like growth factor-I, type 1 receptor, and
      insulin-like growth factor binding protein-4 messenger RNAs within the
      hippocampal formation of young and aged rats. However, quantitative analysis of
      messenger RNA abundance in hippocampal tissue homogenates showed a significant
      age-related increase in type 1 receptor messenger RNA (n = 25; t = -2.5; P <
      0.02). Furthermore, linear regression analysis indicated that type 1 receptor
      messenger RNA abundance was significantly correlated with spatial learning
      impairment in the water maze (r = 0.44; P < 0.03) such that greater behavioral
      impairment was associated with higher type 1 receptor messenger RNA levels in the
      hippocampal formation. Neither insulin-like growth factor-I nor insulin-like
      growth factor binding protein-4 messenger RNA abundance was related to age or
      behavior. However, linear regression revealed a negative correlation between
      insulin-like growth factor-I messenger RNA abundance and type 1 receptor
      messenger RNA abundance in aged hippocampus (r = -0.72, P < 0.01). These data
      indicate that increased hippocampal expression of type 1 receptor messenger RNA
      is associated with aging and cognitive decline. The correlation between type 1
      receptor and insulin-like growth factor-I messenger RNA abundance in the
      hippocampal formation of aged rats suggests that insulin-like growth factor
      availability may influence type 1 receptor expression. However, because no
      overall age difference was found in the amount of insulin-like growth factor-I
      messenger RNA in the hippocampal formation, decreased insulin-like growth factor
      from other sources such as the cerebrospinal fluid and the peripheral circulation
      may be involved in up-regulating type 1 receptor messenger RNA. Alternatively,
      type 1 receptor messenger RNA regulation may be part of a trophic response to the
      degenerative and regenerative events that occur within the hippocampal formation
      during aging.

PMID- 8737420
TI  - The peripheral antinociceptive effect of morphine in a rat model of facial pain.
AB  - The present study compared the peripheral and systemic antinociceptive effect of
      morphine on formalin-induced facial pain behavior in the rat. Formalin (5%, 50
      microliters) was injected subcutaneously into the vibrissal pad of adult rats
      (250-300 g). Morphine sulfate at doses of 100-1000 micrograms was subcutaneously
      injected locally (same area) or systemically (in the neck), 30 min before, or
      simultaneously with, formalin. The typical biphasic face grooming response,
      consisting of an early phasic phase (0-6 min) and a delayed tonic phase (12-42
      min), displayed by control animals, was suppressed by both local and systemic
      administration of morphine; this effect was dose dependent. However, the
      suppression of the early phase with local morphine administration 30 min before
      formalin could be significantly greater (49-52%) than with systemic
      administration, depending on the dose used. Administration of local morphine
      simultaneously with formalin produced up to 34% reduction in the early and an
      additional 32% reduction of the late phases of face grooming, compared to
      systemic injections. Local injection of naloxone (10 micrograms) almost
      completely reversed the antinociceptive effect of 1000 micrograms of morphine
      (early phase 85 +/- 7%, late phase 100 +/- 26% reduction), whereas the same dose
      of naloxone applied systemically (i.p.) produced only partial reversal (early
      phase 29 +/- 16%, late phase 36 +/- 1% reduction). This study further indicates
      that locally administered morphine can exert an analgesic effect superior to
      systemic administration in the case of inflammatory and non-inflammatory pain
      through a peripheral site of action. These results support the clinical use of
      peripheral opioid administration in the treatment of human painful conditions.

PMID- 8737421
TI  - Pre-emptive dynorphin and N-methyl-D-aspartate glutamate receptor antagonism
      alters spinal immunocytochemistry but not allodynia following complete peripheral
      nerve injury.
AB  - The development of chronically painful states following peripheral nerve injury
      may involve different mechanisms depending on the nature and extent of the nerve
      lesion. The altered spinal neurochemistry of two substances, the excitatory amino
      acid glutamate operating via the N-methyl-D-aspartate receptor and the endogenous
      opioid peptide dynorphin, have been implicated in behavioral sequelae that follow
      partial peripheral nerve injury. In addition, dynorphin has nonopioid functions
      which may involve the N-methyl-D-aspartate receptor. We investigated two
      hypotheses: that the development of mechanical allodynia following complete nerve
      injury is not greatly influenced by the N-methyl-D-aspartate receptor, and that
      spinal dynorphin and glutamate expression is interdependent. These studies
      employed sciatic cryoneurolysis, a complete but transient peripheral nerve injury
      that results in a delayed mechanical allodynia beginning 21-28 days after injury.
      Rats were administered dizocipline maleate (MK-801) at 0.25 mg/kg twice per day
      intraperitoneally from days 0-7 or from days 0-21 post-lesion to pre-emptively
      block the N-methyl-D-aspartate receptor. In a separate group of rats, an antibody
      to dynorphin was administered intraperitoneally at 16.6 mg/kg twice per day from
      days 14 to 21 post-lesion. For all groups, the outcome of allodynia behavior was
      assessed using von Frey filaments at 42 days post-lesion and the resulting
      dynorphin and glutamate immunoreactivity in the substantia gelatinosa was
      measured using proportional area stained and relative optical density,
      respectively. Only the 0-7 day MK-801 treatment increased the resulting
      mechanical thresholds significantly (mean +/- S.E.M. 7.0 +/- 1.2 g) when compared
      to saline-injected animals (3.9 +/- 0.6 g). However, this effect did not prevent
      allodynia since baseline thresholds were 12 or 15 g for each group. With regard
      to resulting spinal immunoreactivity, anti-dynorphin antibody treatment
      significantly increased glutamate immunoreactivity when compared to saline
      treated animals (mean relative optical density +/- S.E.M. = 807.2 +/- 3.6 versus
      779.6 +/- 8.3, respectively; P = 0.01) at 42 days post-lesion. We conclude that
      the development of allodynia following sciatic cryoneurolysis peripheral nerve
      injury involved a minimal contribution from N-methyl-D-aspartate receptor
      activity. In addition, this study demonstrated that decreasing available
      dynorphin using antiserum had a significant and lasting effect on spinal
      glutamate expression without altering the outcome of allodynia. These conclusions
      suggest that etiological mechanisms leading to pain behaviors are not equal for
      all nerve injuries, and that altering kappa opioid levels can affect
      glutaminergic pathways at a substantially later time.

PMID- 8737422
TI  - Differential expression of c-fos messenger RNA in the rat spinal cord after
      mucosal and serosal irritation of the stomach.
AB  - Expression of the immediate early gene c-fos is considered to be a marker for
      neuronal activation in the spinal cord in response to afferent input. Since the
      stomach is continually exposed to injurious chemicals, the present study examined
      whether application of acid (0.15 M HCl) and formalin (5%) to the gastric mucosa
      or serosal surface of the stomach stimulates c-fos transcription in the caudal
      thoracic spinal cord of anaesthetized rats. The spinal cord was removed 15, 45 or
      120 min after exposure of the stomach to the noxious chemicals and processed for
      quantitative in situ hybridization autoradiography of c-fos messenger RNA.
      Exposure of the gastric mucosa to acid or formalin failed to increase the
      expression of c-fos messenger RNA in the thoracic spinal cord. Application of
      acid to the serosal surface of the stomach was also unable to stimulate c-fos
      transcription, whereas serosal application of formalin led to substantial
      expression of c-fos messenger RNA in the superficial but also deeper laminae of
      the spinal dorsal horn when examined 45 min, but not 15 or 120 min, post
      stimulation. The highest expression of c-fos messenger RNA was seen when formalin
      was injected subcutaneously into one hindpaw and c-fos transcription was examined
      in the lumbar spinal cord. These data indicate that acute exposure of the gastric
      mucosa to chemical injury does not provide the afferent input which is necessary
      to cause appreciable c-fos transcription in second order neurons within the
      spinal cord. Stimulation of the gastric mucosa by acid and formalin was followed,
      however, by gastric hyperaemia in which spinal afferents releasing vasodilator
      peptides have been implicated. It is concluded, therefore, that acute stimulation
      of nociceptive afferents in the stomach causes local homoeostatic reactions but
      does not necessarily provide afferent input sufficient to recruit spinal
      nociceptive circuits.

PMID- 8737423
TI  - Nicotinic acetylcholine receptors in separate brain regions exhibit different
      affinities for methyllycaconitine.
AB  - The family of nicotinic acetylcholine receptors contains numerous subtypes. Since
      the subunit compositions of most native neuronal nicotinic receptors are unknown,
      an important method for distinguishing subtypes of functional neuronal receptors
      is based on pharmacological criteria, such as affinity for snake toxins. We have
      now examined the affinities of native chick nicotinic receptors for
      methyllycaconitine, a toxin purified from Delphinium. We find that
      methyllycaconitine is a potent antagonist at central nicotinic receptors located
      on Edinger-Westphal neurons, producing nearly complete functional blockade of
      nicotinic responses at 10 nM. In marked contrast, methyllycaconitine is 1000-fold
      less potent at blocking nicotinic responses in the lateral spiriform nucleus.
      Methyllycaconitine inhibits kappa-bungarotoxin-sensitive nicotinic receptors in
      ciliary ganglia at 0.5-1.0 microM. Radioligand binding studies also reveal
      heterogeneity in the affinity of the toxin for nicotinic receptors.
      Methyllycaconitine binds most avidly to [125I] alpha-bungarotoxin sites in brain
      (Ki = 5.4 nM), and is 200-fold less potent at muscle nicotinic receptors (IC50 =
      1.1 microM). The least potent binding of the toxin is to [3H]nicotine sites in
      brain (Ki = 3.7 microM). Methyllycaconitine is thus a useful pharmacological tool
      for distinguishing certain subtypes of native nicotinic receptors. The relatively
      low affinity of the toxin for nicotinic receptors in the lateral spiriform
      nucleus is consistent with the known properties of these receptors, which include
      a high affinity for [3H]nicotine and a lack of sensitivity to alpha- and kappa
      bungarotoxin. On the basis of high affinity for methyllycaconitine and
      insensitivity to alpha-bungarotoxin, the nicotinic receptors in the Edinger
      Westphal nucleus are unlike any previously described nicotinic receptor subtype.

PMID- 8737424
TI  - The serotonergic agent fluoxetine reduces neuropeptide Y levels and neuropeptide
      Y secretion in the hypothalamus of lean and obese rats.
AB  - Evidence suggests that serotonin and neuropeptide Y neurons in the hypothalamus,
      which respectively inhibit and stimulate food intake, may interact to control
      energy homoeostasis. We therefore investigated the effects of fluoxetine, which
      inhibits serotonin reuptake, on food intake and the activity of the neuropeptide
      Yergic arcuato-paraventricular projection in lean Wistar and Zucker rats. We also
      studied its effects in obese Zucker rats, in which obesity is postulated to be
      due to overactivity of the arcuato-paraventricular projection. Fluoxetine
      significantly reduced food intake in lean and obese rats, both during continuous
      subcutaneous infusion and (10 mg/kg/day for seven days) and acutely after a
      single injection (10 mg/kg). Fluoxetine also significantly reduced neuropeptide Y
      levels in the paraventricular nucleus, a major site of neuropeptide Y release
      which is highly sensitive to the appetite-stimulating actions of neuropeptide Y.
      Push-pull sampling in lean and fatty Zucker rats showed that neuropeptide Y
      secretion in the paraventricular nucleus was significantly reduced after acute
      fluoxetine treatment. Furthermore, seven days fluoxetine treatment prevented the
      significant increases in hypothalamic neuropeptide Y messenger RNA which were
      induced in lean rats by food restriction which precisely matched the hypophagia
      induced by the drug. We conclude that fluoxetine inhibits various aspects of the
      activity of the neuropeptide Yergic arcuato-paraventricular neurons, and suggest
      that reduced neuropeptide Y release in the paraventricular nucleus may mediate,
      at least in part, the drug's hypophagic action. We further suggest that serotonin
      may influence food intake and energy balance by inhibiting the arcuato
      paraventricular projection, and that the two neurotransmitters may act together
      to regulate feeding and energy homoeostasis.

PMID- 8737425
TI  - Differential cellular pattern of gene expression for two distinct cGMP-inhibited
      cyclic nucleotide phosphodiesterases in developing and mature rat brain.
AB  - Cyclic GMP-inhibited phosphodiesterases are characterized by sensitivity of cAMP
      hydrolysis to inhibition by cGMP. This phosphodiesterase family contains at least
      two different isoforms (PDE3A and PDE3B) encoded by distinct genes and serving
      tissue-specific roles in regulation of lipolysis, glycogenolysis, myocardial
      contractility, and smooth muscle relaxation. Our previous work indicated an
      abundance of these two phosphodiesterase messenger RNAs in the embryonic rat
      brain, and therefore, to elucidate the potential functions of these enzymes in
      brain development as well as in mature brain function, the present study mapped
      cellular patterns of gene expression for these two enzymes from embryonic day 15
      to adulthood using in situ hybridization histochemistry. Phosphodiesterase 3B
      isoform messenger RNA is uniformly expressed in germinal neuroepithelium and
      mature neurons, with distribution generally reflecting cell density.
      Phosphodiesterase isoform 3A messenger RNA, in contrast, demonstrates striking
      spatiotemporal specificity of expression, with three distinct patterns being
      evident. Firstly, this mRNA is highly abundant in both primary and secondary
      neuroepithelial germinal zones. Secondly, during early postnatal development
      PDE3A mRNA is transiently but highly expressed in neurons localized in basal
      forebrain, deep cerebellar, pontine, interpeduncular and a variety of thalamic,
      midbrain and brainstem nuclei. Thirdly, PDE3A mRNA is focally expressed in
      isolated large striatal and hippocampal neurons from the perinatal period without
      attenuation into adulthood. In summary, two cGMP-inhibited phosphodiesterase
      isoforms show distinctive patterns of gene expression in brain: PDE3B gene
      expression is uniform without evidence of system specificity or developmental
      stage specificity, suggesting that this isoform has a constitutive role in
      neuroepithelial metabolism, while PDE3B gene expression demonstrates a high level
      of spatiotemporal heterogeneity, suggesting that this isoform subserves a variety
      of developmental stage-specific and system-specific functions.

PMID- 8737426
TI  - Expression of an epithelial membrane glycoprotein by neurons arising from the
      human olfactory plate through development.
AB  - Human terminal-vomeronasal neural crest cells began to express a 34,000 molecular
      weight epithelial membrane glycoprotein, which was detected by the mouse
      monoclonal antibody Ber-EP4 soon after their migration into the olfactory plate.
      Expression of this antigen continued in neurons arising from these cells, which
      were olfactory sensory neurons and luteinizing hormone-releasing hormone
      producing neurons migrating into the brains of the embryos of approximately 44-52
      postovulatory days. Ber-EP4 immunoreactivity appeared over the entire surface
      membranes of these neurons, including their processes, not only in their
      extracerebral portions, but also within the brain parenchyma from 48 to 53
      postovulatory days. Ber-EP4 immunoreactivity of these migrating neurons became
      weaker as they matured into luteinizing hormone-releasing hormone-producing
      neurons and disappeared from the postnatal hypothalamic neurons; however, it
      remained in the primary sensory nerve fibers throughout postnatal life. Except
      for the neurons arising from the olfactory plate, no other human neurons express
      this epithelial antigen during the course of development. The mechanism and
      significance of the expression of this antigen in mature sensory neurons remains
      unclear, but the intramucosal location and morphological kinship of these neurons
      to epithelial cells may be related to this phenomenon. The results of the present
      study indicate that neurons arising from the olfactory plate are distinct from
      other neurons by having a 34,000 molecular weight epithelial membrane
      glycoprotein that can be detected by the mouse monoclonal antibody, Ber-EP4,
      during the embryonic stage. This antigen disappears from the luteinizing hormone
      releasing hormone-producing neurons concomitant with maturation, but is preserved
      in the olfactory primary sensory nerve throughout postnatal life.

PMID- 8737427
TI  - Vincristine disturbs spontaneous firing of the afferent nerve fibre in ampullary
      electroreceptor organs.
AB  - Ampullary electroreceptor organs of the catfish were apically exposed to 0.3 mM
      vincristine in order to investigate the part played by the microtubular system in
      stimulus transduction. The main effects were repetitive firing of the afferent
      fibre, a reduction of the mean spontaneous activity and a reduction of the spike
      amplitude two to four days after exposure to vincristine. The mean sensitivity
      was less susceptible to vincristine than the spontaneous activity. Since the
      shape of the frequency curves remained unchanged and similar effects as described
      above were also observed after denervation, we conclude that vincristine most
      likely does not affect electroreceptor cell functioning, but causes degeneration
      of the afferent fibre.

PMID- 8737428
TI  - Inappropriate distribution of medicines by professionals in developing countries.

PMID- 8737429
TI  - Antibiotic use in a periurban community in Mexico: a household and drugstore
      survey.
AB  - In developing countries, antibiotics are the most common drugs sold, and some
      data suggest that they are frequently misused. In order to describe the pattern
      of antibiotic use in a periurban community in Mexico City, 1659 randomly-selected
      households were visited and an interview with the housewife was carried out. Six
      local drugstores also were selected at random. A social worker made six visits to
      each pharmacy, observed the events during the purchase of the drug and applied a
      structured questionnaire to the customer immediately after the transaction. Of
      8279 individuals, 425 (5%) said that they had used at least one antimicrobial in
      the preceding 2 weeks and antibiotics were the majority (29%) of the drug sales.
      The main perceived reasons for drug use were acute respiratory tract ailments and
      gastroenteritis. Interviewees reported that antibiotic therapy was given in 27%
      of respiratory diseases and in 37% of all diarrheal episodes. The drugs most
      commonly reported were: penicillins, erythromycin, metronidazole, neomycin,
      cotrimoxazole and tetracyclines. While self-medication and drug purchases without
      medical prescription were common, the majority of antibiotics were prescribed by
      a physician. Approximately two thirds of individuals using an antibiotic said
      they had used it for less than 5 days and 72% of the purchases were for
      insufficient quantities of drugs. Our data suggest that antibiotics are
      frequently misused and they support the need to assess the determinants of self
      medication, health-seeking behavior and physician prescribing practices. The need
      for effective educational programs to improve prescribers' decisions is stressed.

PMID- 8737430
TI  - Availability of over-the-counter drugs for arthritis in Sao Paulo, Brazil.
AB  - Seventy pharmacies located in Sao Paulo were randomly selected and visited. Seven
      researchers posed as ordinary clients presenting with a standardized complaint of
      symptoms according to a scenario previously defined. The client asked for
      medicines to relieve his/her pain or discomfort. After the seller's suggestion
      the client asked for 2 drugs randomly selected from a drug list containing 30
      trademarked drugs commonly prescribed to arthritis patients. These drugs should
      be available only on prescription. In only 12.8% of the pharmacies did the seller
      initially suggest the client see a physician. The sellers "prescribed' non
      steroid anti-inflammatory drugs (NSAID), vitamins, analgesics (AN) and
      corticosteroids (CO) in respectively 42.8, 20.0, 14.3 and 5.7% of the visits.
      From the drug list, the client secured 67.7% of the NSAID, 65.0% of the CO and
      20.0% of the sedatives without presenting a prescription. Pharmacy sellers
      usually comply with the clients demands. Future studies should aim at the
      evaluation of interventions to reduce the availability of the over-the-counter
      drugs for arthritis.

PMID- 8737431
TI  - Drug prescribing practices of general practitioners and paediatricians for
      childhood diarrhoea in Karachi, Pakistan.
AB  - Observations were made of 996 encounters between children with diarrhoea and
      practitioners (28 paediatricians, 62 general practitioners) in Karachi, Pakistan.
      Oral rehydration salt (ORS) was prescribed in more than 50% of encounters by 53%
      of general practitioners (GPs) and 61% of paediatricians. Sixty-six percent of
      GPs and 50% of paediatricians prescribed antibacterials, 60% of GPs and 28% of
      paediatricians prescribed antidiarrhoeals and 39% of GPs and 32% of
      paediatricians prescribed antiamoebics in more than 30% of their encounters.
      Looking at all the encounters, we observed that ORS was prescribed in 52 and 51%,
      antibacterials in 41 and 36%, antidiarrhoeals in 48 and 29%, and antiamoebics in
      26 and 22% of encounters by GPs and paediatricians, respectively, Cotrimoxazole
      was the most frequently prescribed antibacterial by both types of practitioners.
      Antidiarrhoeals were prescribed more often by GPs than by paediatricians. In 77%
      of their encounters, GPs dispensed drug formulations known as "mixtures' made in
      their own dispensing corners. The mean duration of encounters between patients
      and GPs was 3 +/- 2 minutes and between patients and paediatricians was 9 +/- 4
      minutes. These results indicate inadequate prescription of ORS and excessive
      prescription of antibacterials, antidiarrhoeals and antiamoebics. Intervention
      strategies need to be planned to improve the prescribing practices of both
      groups.

PMID- 8737432
TI  - Factors influencing physicians' prescribing behaviour in the treatment of
      childhood diarrhoea: knowledge may not be the clue.
AB  - Proper diarrhoea treatment has received greater attention during the last 10
      years. However, the unjustified use of medicines to treat simple episodes of
      acute diarrhoea continues to divert attention and available resources away from
      appropriate treatment. A study to identify the factors determining prescribing
      practices for diarrhoea treatment was carried out in a peri-urban part of Lima,
      Peru in 1991. Physicians were interviewed, and then their practice was assessed
      by visits of confederates with healthy children described as ill, by interviews
      with mothers of sick children leaving the clinic, or by both of these methods.
      Physicians' reported practices in treating diarrhoea cases were compared to their
      actual practices. Although physicians' knowledge of drug management seemed to
      influence the low frequency of prescription of antidiarrhoeal drugs, it did not
      have the same influence on prescription of antimicrobials. Our results suggest
      that the diagnostic process and consequently the treatment decision do not follow
      a scientific rationale for this illness. The physicians' prescribing practices
      seemed to be more related to agreement with social expectations and the
      caretakers' perception of the physicians' role than they were to the standard
      biomedical rules of diarrhoea management.

PMID- 8737433
TI  - Retail pharmacies in developing countries: a behavior and intervention framework.
AB  - Retail pharmacies in developing countries are one of the most important sources
      of advice on pharmaceuticals. Among the reasons the clients give are ease of
      access; availability of medicines; quality of service (no waiting and convenient
      hours of operation); and cheaper products, availability of credit, or the option
      to buy drugs in small amounts. However, the appropriateness of prescribing by
      retail pharmacy staff has been found to be far from acceptable. In childhood
      diarrhea, for example, oral rehydration salts (ORS), the appropriate diarrhea
      treatment, are recommended much less than pharmaceuticals of limited value, such
      as antimotility agents, adsorbents, etc. Little information is available for
      reasons underlying such behaviors. In this paper, we present a conceptual
      framework in which to analyze factors that may affect retail pharmacy
      prescribing, and we suggest strategies for behavior change. We developed this
      framework after examining relevant literature on retail pharmacy prescribing. We
      propose that pharmacy factors, client factors, physician practice and regulatory
      factors are the four sets of important factors for understanding pharmacy
      prescribing behavior. For intervention, we present four types of interventions
      which could be used for changing the behavior of pharmacy staff: information
      alone, persuasion, incentives and coercion. The behavior and intervention
      frameworks presented in this paper should also help in guiding further research
      in this area. For example, new information on the effects of ownership type,
      availability vs actual role of professional staff and authority structure on
      pharmacy treatment behaviors would be useful areas for future research.
      Similarly, additional research is needed on the comparative effects of coercive,
      persuasive and incentive strategies on pharmacy treatment behaviors.

PMID- 8737434
TI  - Small group intervention vs formal seminar for improving appropriate drug use.
AB  - In an attempt to evaluate the efficacy of different methods of interventions to
      improve the appropriate use of drugs for acute diarrhoea, a controlled study has
      been carried out in 6 districts in Yogyakarta and Central Java provinces,
      Indonesia. This study was designed to investigate the impacts of two different
      methods of educational intervention, i.e. a small group face-to-face intervention
      and a formal seminar for prescribers, on prescribing practice in acute diarrhoea.
      The districts were randomly assigned into 3 groups and 15 health centers were
      selected from each district. Prescribers in Group 1 underwent a small group face
      to-face intervention conducted in the respective health center. Those in Group 2
      attended a formal seminar conducted at the district level. Prescribers in Group 3
      served as the control group. Both interventions were given on a single occasion
      without follow-up supervision or monitoring. Written information materials on the
      appropriate management of acute diarrhoea were developed and were provided to all
      prescribers in the intervention groups. Focus group discussions (FGDs) involving
      prescribers and consumers in the 6 districts were carried out to identify various
      underlying motivations of drug use in acute diarrhoea. The findings of the FGDs
      were used as part of the intervention materials. To evaluate the impacts of these
      interventions on prescribing practice, a prescribing survey for patients under
      five years old with acute diarrhoea was carried out in health centers covering 3
      month periods before and after the intervention. The results showed that both
      interventions were equally effective in improving the levels of knowledge of
      prescribers about the appropriate management of acute diarrhoea. They were also
      partially effective in improving the appropriate use of drugs, reducing the use
      of non-rehydration medications. There was a highly significant reduction of
      antimicrobial usage either after small-group face-to-face intervention (77.4 +/-
      2.7% to 60.4 +/- 2.9%; P < 0.001) or formal seminar (82.3 +/- 3.0% to 72.3 +/-
      3.6%; P < 0.001), and the former caused significantly (P < 0.001) greater
      reduction than the latter. There was also a significant (P < 0.01) reduction in
      the usage of antidiarrhoeals after both interventions, i.e. from 20.3 +/- 3.7% to
      12.5 +/- 3.3% (P < 0.01) after face-to-face intervention and from 48.5 +/- 4.1%
      to 27.0 +/- 4.3% (P < 0.01) after seminar. However, the formal seminar had a
      significantly (P < 0.01) greater impact than the small group face-to-face
      intervention. There was also a trend toward increased oral rehydration solution
      (ORS) usage after both interventions, but this did not achieve the level of
      statistical significance (P > 0.05). No changes were observed in the control
      group. Although the small group face-to-face intervention did not appear to offer
      greater impacts over large seminars in improving the appropriate use of drugs in
      acute diarrhoea, since the unit cost of training is far less costly than the
      seminar, it might be feasibly implemented in the existing supervisory structure
      of the health system.

PMID- 8737435
TI  - Effect of training on the clinical management of malaria by medical assistants in
      Ghana.
AB  - Malaria accounts for over 40% of all outpatient consultations in Ghana. A common
      drug use problem associated with its treatment with chloroquine is over- and
      under-dosage and a preference for the intramuscular route of administration.
      Inadequate treatment is an important factor in the selection of resistant strains
      of malaria parasites. To ensure the proper management of diseases at health
      centres the Ministry of Health instituted an in-service training programme for
      medical assistants in 1987. We evaluated the effect of this training on the
      clinical management of malaria using a quasi-experimental design. Three methods
      of data collection were used; prescription survey, assessment questionnaires and
      focus group discussions. Our findings revealed that gains in knowledge following
      the training had deteriorated within a year. There was also a discrepancy between
      knowledge and practice of malaria treatment. This was shown by over- and under
      dosing of chloroquine in children and adults respectively. There was also
      overwhelming preference (85% of all cases) for injections and a high tendency
      towards polypharmacy (average of five drugs per visit). The motivating reasons
      for these were mainly socio-cultural and included patient demand and attitudes,
      prescriber self interests and stereotypes and the daily practical challenges of
      the community. While paying greater attention to supervision of clinical work at
      health posts, consideration must be given to socio-cultural context of drug use
      in any such future training programmes if rational use of drugs is to be
      achieved.

PMID- 8737436
TI  - Interactional group discussion: results of a controlled trial using a behavioral
      intervention to reduce the use of injections in public health facilities.
AB  - Injections are commonly overused in Indonesia. More than 60% of patients
      attending public health facilities receive at least one injection, which
      increases clinical risk and has adverse economic impact. This study assesses the
      efficacy of an innovative behavioral intervention, the Interactional Group
      Discussion (IGD), for reducing the overuse of injections. This study was a
      controlled trial in a single district with 24 public health centers randomized to
      intervention and control groups. Prescribers in the intervention group were
      invited to one IGD, each of which consisted of 6 prescribers and 6 patients; a
      total of 24 IGDs were held in a 4-week period, and all invited prescribers
      participated. The groups, which lasted 90-120 minutes, were facilitated by a
      behavioral scientist and a clinician, who also served as a scientific resource
      person. The hypothesized mechanism of behavior change involved reality testing
      prescribers' assumptions about patient beliefs, imparting scientific information
      about injection efficacy, and establishing peer norms about correct behavior.
      Outcomes were measured by a retrospective prescribing survey covering the periods
      3 months before and 3 months after the intervention, with samples of 100
      prescriptions per center per month. Rates of injection and average number of
      drugs per prescription were computed separately for each center, and t-tests were
      used to compare pre-post changes in outcomes in both groups. Results showed a
      significant decrease in injection use from 69.5 to 42.3% in the intervention
      group, compared to a decrease from 75.6 to 67.1% among controls [-18.7.0%
      intervention vs control, 95% CI = (-31.1%, -6.4%), P < 0.025]. There was also a
      significant reduction in average number of drugs per prescription [-0.37 drugs
      prescribed per patient, 95% CI = (-0.04, -0.52), P < 0.05], indicating that
      injections were not substituted with other drugs. We conclude that the IGD
      significantly reduces the overuse of injections. It is suggested to try out other
      behavioral interventions to improve the rational use of drugs.

PMID- 8737437
TI  - Improving physician prescribing patterns to treat rhinopharyngitis. Intervention
      strategies in two health systems of Mexico.
AB  - To improve prescribing practices for rhinopharyngitis, an interactive educational
      intervention and a managerial intervention were carried out in 18 primary care
      facilities in metropolitan Mexico City. Four family medicine clinics of the
      Mexican Social Security Institute (IMSS) and 14 health centres of the Ministry of
      Health (SSA) were included. A quasi-experimental design was employed. One hundred
      and nineteen physicians (IMSS 68, SSA 51) participated. Sixty-five physicians
      (IMSS 32, SSA 33) were in the study group, while 54 were in the control group
      (IMSS 36, SSA 18). The study had four stages: (I) baseline, to evaluate the
      physicians' prescribing behaviour for rhinopharyngitis; (II) intervention, using
      an interactive educational workshop and a managerial peer review committee; (III)
      post-intervention evaluation of short-term impact; and (IV) follow-up evaluation
      of long-term effect 18 months after the workshop. The control group did not
      receive any intervention but was evaluated at the same time as the study group.
      At baseline, most patients in both institutions received antibiotic prescriptions
      (IMSS 85.2%, SSA 68.8%). After the workshop, the percentage of patients receiving
      antibiotic prescriptions in the IMSS went from 85.2% to 48.1%, while in the SSA
      it went from 68.8% to 49.1%. Appropriateness of treatment was analyzed using the
      physician as the unit of analysis. At baseline, 30% of IMSS physicians in the
      study group treated their patients appropriately. After the intervention, this
      percentage increased to 57.7%, and at the 18-month follow-up it was 54.2%. The
      SSA study group increased the appropriate use of antibiotics from 35.7% to 46.2%,
      with this percentage falling to 40.9% after the 18-month follow-up period. In the
      control group there were no significant changes in prescribing patterns with
      respect to either the prescribing of antibiotics or the appropriateness of
      treatment. The intervention strategies were successful in both institutions.
      Forty per cent of physicians improved their prescribing practices after the
      workshop, with this change remaining in 27.5% of them throughout the follow-up
      period. On the other hand, 42.5% of the physicians did not change their
      prescribing practices after the intervention. The rest (17.5%) showed appropriate
      prescribing practices during all the stages of the study. We conclude that it is
      possible to improve the physicians' prescribing practices through interactive
      educational strategies and managerial interventions. This type of intervention
      can be an affordable way to provide continuing medical education to primary care
      physicians who do not have access to continuing educational activities, and to
      improve the quality of care they provide.

PMID- 8737438
TI  - Assessing the impact of a regulatory intervention in Pakistan.
AB  - In 1990 paediatric formulations of antimotility drugs were deregistered in
      Pakistan. Although preliminary research data suggests the incidence of paralytic
      ileus in children suffering from acute diarrhoea has fallen, cases continue to be
      recorded. A small-scale survey conducted in 1993 to assess the effectiveness of
      the regulatory intervention conclusively proved that while the deregistered
      products had been successfully withdrawn from the overwhelming majority of retail
      outlets, blackmarketing of a paediatric antimotility drug was taking place in one
      city. The results also indicated that throughout the country the deregistered
      formulations were being substituted by other irrational therapies, including the
      misuse of adult formulations. As a regulatory intervention, therefore,
      deregistration needs to be accompanied by efforts to change patient attitudes and
      physician prescribing habits.

PMID- 8737439
TI  - pH regulation and proton signalling by glial cells.
AB  - The regulation of H+ in nervous systems is a function of several processes,
      including H+ buffering, intracellular H+ sequestering, CO2 diffusion, carbonic
      anhydrase activity and membrane transport of acid/base equivalents across the
      cell membrane. Glial cells participate in all these processes and therefore play
      a prominent role in shaping acid/base shifts in nervous systems. Apart from a
      homeostatic function of H(+)-regulating mechanisms, pH transients occur in all
      three compartments of nervous tissue, neurones, glial cells and extracellular
      spaces (ECS), in response to neuronal stimulation, to neurotransmitters and
      hormones as well as secondary to metabolic activity and ionic membrane transport.
      A pivotal role for H+ regulation and shaping these pH transients must be assigned
      to the electrogenic and reversible Na(+)-HCO3-membrane cotransport, which appears
      to be unique to glial cells in nervous systems. Activation of this cotransporter
      results in the release and uptake of base equivalents by glial cells, processes
      which are dependent on the glial membrane potential. Na+/H+ and Cl-/HCO3
      exchange, and possibly other membrane carriers, accomplish the set of tools in
      both glial cells and neurones to regulate their intracellular pH. Due to the pH
      dependence of a great variety of processes, including ion channel gating and
      conductances, synaptic transmission, intercellular communication via gap
      junctions, metabolite exchange and neuronal excitability, rapid and local pH
      transients may have signalling character for the information processing in
      nervous tissue. The impact of H+ signalling under both physiological and
      pathophysiological conditions will be discussed for a variety of nervous system
      functions.

PMID- 8737440
TI  - Plasticity of cutaneous primary afferent projections to the spinal dorsal horn.
AB  - Reorganization of the somatotopic map in the spinal dorsal horn may be elicited
      by a variety of deafferenting lesions, including transection of peripheral nerves
      or dorsal roots, or the application of neurotoxins. While such lesions give rise
      to a variety of neurochemical and morphological changes in the dorsal horn,
      collateral sprouting of intact primary afferents appears to be minimal. Recently,
      intraaxonal injection of neurobiotin has allowed visualization of the entire
      spinal arborization of single A beta primary afferent fibers in animals where the
      somatotopy of the relevant region of dorsal horn has also been mapped. In
      contrast to the somatotopic precision of the terminal fields of peripheral nerves
      suggested by transganglionic tracing, these studies have shown that afferents
      make connections many millimeters rostral and caudal to the region where their
      receptive field is represented in the somatotopic map. Intracellular recording
      from dorsal horn neurons has further shown that these long-ranging projections
      make functional, but weak, synaptic connections. Thus the functional somatotopic
      reorganization that follows nerve lesions in mature animals might be explained
      simply by an increased synaptic efficacy of these existing projections. In
      contrast to the negligible sprouting of intact A beta primary afferents, those
      undergoing axonal regeneration exhibit dense collateral sprouting into
      deafferented regions of the dorsal horn, particularly the superficial laminae,
      where the terminal arbors of many small (A delta and C) nociceptive afferent
      fibres degenerate following peripheral nerve lesions. The inappropriate
      connections made by these collateral sprouts may partly underlie the painful
      sequelae of nerve injury in man.

PMID- 8737441
TI  - Ischemia and lesion induced imbalances in cortical function.
AB  - Cortical structures are often critically affected by ischemic and traumatic
      lesions which may cause transient or permanent functional disturbances. These
      disorders consist of changes in the membrane properties of single cells and
      alterations in synaptic network interactions within and between cortical areas
      including large-scale reorganizations in the representation of the peripheral
      input. Prominent functional modifications consisting of massive membrane
      depolarizations, suppression of intracortical inhibitory synaptic mechanisms and
      enhancement of excitatory synaptic transmission can be observed within a few
      minutes following the onset of cortical hypoxia or ischemia and probably
      represent the trigger signals for the induction of neuronal hyperexcitability,
      irreversible cellular dysfunction and cell death. Pharmacological manipulation of
      these early events may therefore be the most effective approach to control
      ischemia and lesion induced disturbances and to attenuate long-term neurological
      deficits. The complexity of secondary structural and functional alterations in
      cortical and subcortical structures demands an early and powerful intervention
      before neuronal damage expands to intact regions. The unsatisfactory clinical
      experience with calcium and N-methyl-D-aspartate antagonists suggests that this
      result might be achieved with compounds that show a broad spectrum of actions at
      different ligand-activated receptors, voltage-dependent channels and that also
      act at the vascular system. Whether the same therapy strategies developed for the
      treatment of ischemic injury in the adult brain may be applied for the immature
      cortex is questionable, since young cortical networks with a high degree of
      synaptic plasticity reveal a different response pattern to hypoxic and ischemic
      insults. Age-dependent molecular biological, morphological and physiological
      parameters contribute to an enhanced susceptibility of the immature brain to
      these noxae during early ontogenesis and have to be investigated in more detail
      for the development of adequate clinical therapy.

PMID- 8737442
TI  - Endothelium-dependent hyperpolarization of vascular smooth muscle: role for a non
      nitric oxide synthase product.
AB  - There is now a considerable evidence that indicates that there is non
      NO/prostanoid mediated vasodilation/hyperpolarization mechanism in a variety of
      blood vessels from different species. It is argued that a factor, EDHF, is
      responsible for mediating these cellular events and, like NO, EDHF is synthesized
      and released, in a Ca(2+)-dependent manner, from endothelial cells and activates
      vascular K+ channel(s) with the predominant evidence suggesting K(Ca)
      (iberiotoxin and/or apamin sensitive) though this remains to be absolutely
      confirmed. A number of studies also indicate that a cytochrome P-450 metabolite
      of arachidonic acid, namely an epoxyeicosatrienoic acid, may serve as the
      chemical messenger between endothelial and vascular smooth muscle cells. Evidence
      confirming that there is chemical transmission between endothelial and vascular
      smooth muscle cells is, however, minimal. Although significant progress has been
      recently made, much needs to be discovered concerning the nature, synthesis,
      release, vascular effects as well as the role of EDHF in normal and diseased
      vascular tissue.

PMID- 8737443
TI  - Molecular modeling of interactions between tetrahydroprotoberberines and dopamine
      receptors.
AB  - AIM: To build up the structure models of dopamine receptors, then combined with
      the receptor models, to investigate the action mechanism of
      tetrahydroprotoberberines (THPB) on dopamine receptors at the molecular level.
      METHODS: Using the three-dimensional structure of bacteriorhodopsin as a
      template, we have constructed dopamine D1 and D2 receptor models on computer. l
      Stepholidine was selected as the leading compound of THPB and docked into D1 and
      D2 receptor active sites. RESULTS: After manual adjustment and energy
      minimization, the ligand-receptor interaction models were achieved. Based on
      these models, the possible action mechanism of THPB on dopamine receptors was
      suggested that the protonated N atom of THPB form electrostatic interaction and
      hydrogen-bonding interaction with residue Asp in TM3 of the receptor, the two
      substituents in D ring of THPB form hydrogen-bonding interactions with two Ser
      residues in TM5 of the receptor, and the aryl groups form pi-pi interactions with
      some aryl residues of the receptor around ligand. CONCLUSION: Our ligand-receptor
      interaction models should be helpful for rational design of more potent drugs.

PMID- 8737444
TI  - Two-state stochastic models for memory in ion channels.
AB  - AIM: To study quantitatively the memory existing in ion channels. METHODS:
      Stochastic processes were used to model 2 categories of memory (short-term and
      long-term) by persisting in the standpoint of two-state, instead of multiple
      states, but with different transition mechanism. RESULTS: A two-state Markov
      process with constant transition intensities well fitted the short-term memory
      and a two-state Markov process within a kind of random environment well fitted
      the long-term memory. Statistical procedures for parameter estimation were
      proposed and demonstrated with 2 real examples on the channels of PC12 cells.
      CONCLUSION: The memory in ion channels can be quantitatively modelled as
      stochastic process with 2 states.

PMID- 8737445
TI  - (-)-stepholidine vs 12-chloroscoulerine enantiomers on firing activity of
      substantia nigral dopamine neurons.
AB  - AIM: To compare the potencies between (-)-stepholidine ((-)-SPD) and 12
      chloroscoulerine (CSL) enantiomers on firing of substantia nigra (SN) dopamine
      (DA) neurons. METHODS: Extracellular single unit recordings in paralyzed rats.
      RESULTS: In rats, (-)-SPD, (-)-, ( +/- )-, and (+)-CSL attenuated i.v.
      apomorphine (Apo, 10 micrograms.kg-1)-induced inhibition on firing of DA cell,
      and their ED50 values were 15.1 (11.9-19.4), 7.8 (7.0-8.7), 12.6 (2.0-17.9)
      micrograms.kg-1, and 2.9 (2.6-3.3) mg.kg-1, respectively. Thus, (-)-CSL was 1
      time more potent than (-)-SPD and 371 times more potent than (+)-CSL on D2
      receptors. In reserpinized rats, (-)-SPD, (-)-, ( +/- )-, and (+)-CSL blocked the
      inhibition caused by i.v. 4 mg.kg-1 SKF-38393, with ED50 values of 0.53 (0.51
      0.55), 0.51 (0.43-0.60), 1.2 (0.7-2.0), and 5.9 (4.9-7.1) mg.kg-1, respectively.
      The potency of (-)-CSL was similar to that of (-)-SPD on D1 receptors and 11
      times higher than that of (+)-CSL. CONCLUSION: CSL enantiomers are D1/D2 mixed
      antagonists as (-)-SPD. (-)-CSL is the most, while (+)-CSL is the least, potent
      one among them.

PMID- 8737446
TI  - Dopamine-induced ionic currents in acutely dissociated rat neurons of CNS.
AB  - AIM: To determine whether or not the dopamine (DA) can induce ionic current in
      single neuron acutely dissociated from different central areas including
      striatum, ventral tegmental area (VTA), substantia nigra pars compacta (SNC) and
      hippocampal CA1 area. METHODS: Using a new patch-clamp whole-cell recording
      technic, namely nystatin-perforated whole-cell configuration under voltage-clamp
      mode. RESULTS: In 36 single neurons isolated from the striatum and VTA, DA 10
      1000 mumol.L-1 was quite diverse to elicit ionic current responses. In 19 SNC
      neurons, 5 neurons (26%) response to 1 mmol.L-1 DA represented as a small outward
      current (11.3 +/- 2.4 pA) at a holding potential (V(H)) of -20 mV. In 25 of 69
      (36%) examined hippocampal CA1 pyramidal neurons, however, application of DA
      induced 3 types of current responses: outward current (8 neurons) accompanied
      with an increase of membrane conductance, slow inward current (5 neurons) with an
      decrease of membrane conductance and outward-following inward current (12
      neurons) at a V(H) of -20 mV. The concentration-response relationship of DA
      induced currents showed the typical sigmoid shape with the threshold dose, being
      the maximum response dose are 3 mumol.L-1 and 1 mmol.L-1 respectively. The
      current-voltage (I-V) relationship of DA-induced responses did not show any
      voltage-dependent manner and the reversal potential (E(DA)) was close to the
      equilibrium potential of potassium (E(K)) calculated with the Nernst equation.
      TEA 5 mol.L-1 effectively inhibited the DA-induced response. CONCLUSION: These
      results suggest that DA-induced outward current is carried by K+ in single
      hippocampal CA1 pyramidal neuron.

PMID- 8737447
TI  - Distributions of mu and delta opioid receptors in central nervous system of SHR
      rats and normotensive WKY rats.
AB  - AIM: To compare the distributions of opioid receptor subtypes in central nervous
      system of spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto
      (WKY) rat. METHODS: [3H] Ohmefentanyl (OMF), [3H]N-methyl-N-[7-(I-pyrrolidinyl)-1
      oxaspiro (4,5)dec-8-yl] benzeneacetamide (U-69593) and [3H]etorphine after
      suppression of mu and kappa-sites by 15 mumol.L-1 each of unlabeled OMF and trans
      (1R,2R)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]-benzeneacetamide
      hydrochloride (U-50 488H) were used as ligands for mu, kappa, and delta opioid
      receptor subtypes in autoradiography, respectively. RESULTS: Delta receptors had
      an increase in hypothalamic nuclei, periaqueductal gray, caudate and
      interpeduncular nuclei, and a decrease in substantia nigra in SHR than in those
      of WKY rat. Mu receptors were less concentrated in basolateral amygdaloid
      nucleus, habenular nuclei and nucleus of solitary tract of SHR than in those of
      WKY rats. Kappa receptor density was not checked out in the present study.
      CONCLUSION: Distribution of opioid receptor subtypes is related to hypertension
      of SHR, and delta opioid receptor is more important than mu opioid receptor in
      the maintenance of hypertension in SHR.

PMID- 8737448
TI  - Modulatory effects of gonadorelin on GABA-induced depolarization and GABA
      activated current in rat spinal ganglion neurons.
AB  - AIM: To explore the modulatory effects of gonadorelin on GABA-induced
      depolarization and GABA-activated current in membrane of rat primary sensory
      neurons. METHODS: Intracellular recordings and whole-cell patch clamp techniques
      were performed on neurons in rat spinal ganglia (SG) preparation and neurons
      freshly isolated from rat SG, respectively. Drugs were applied by superfusion
      and/or by bath application. RESULTS: In the majority of neurons GABA (10 mumol.L
      1 -1 mmol.L-1) induced a depolarization, which was blocked by bicucullin (100
      mumol.L-1). Pretreatment with gonadorelin (50 mumol.L-1) decreased the GABA
      induced depolarization by 79 +/- 22% (n = 29), while gonadorelin elicited no
      effect or slight depolarization alone. In 6 of 11 cells, GABA-activated currents
      were also inhibited by pretreatment with gonadorelin (50 mumol.L-1), while in 5
      of 11 cells, there was no change or a slight potentiation. CONCLUSION:
      Gonadorelin exerts an inhibitory effect on GABA-induced depolarization and GABA
      activated current in the primary sensory neurons.

PMID- 8737449
TI  - Effect of desipramine on spontaneous activity of hippocampal CA1 neuron after
      transient cerebral ischemia in rats.
AB  - AIM: To study the spontaneous firing of CA1 neurons in rat hippocampus after
      transient cerebral ischemia and the effect of desipramine (Des) on the post
      ischemic electric activity of CA1 neurons. METHODS: Single-unit extracellular
      recordings were performed in rats on d 3 after 10 min of cerebral ischemia by
      occlusion of 4 arteries. Des and saline were injected into a tail vein. The
      histological changes of CA1 neurons was assessed by the neuronal density of the
      CA1 sector. RESULTS: The spontaneous firing rate of CA1 neurons on d 3 after
      ischemia was enhanced in comparison with the control value. Des (0.2 and 0.4
      mg.kg-1, i.v., n = 5 & 6, respectively) reduced dose-dependently the increase of
      firing rate with maximal inhibition by 6 min (58% & 85%) to 9 min (69% & 94%) (vs
      vehicle group, P < 0.01). About 50% cells in CA1 region showed necrotic changes.
      CONCLUSION: Des antagonized the hyperexcitability of CA1 neurons after cerebral
      ischemia.

PMID- 8737450
TI  - Effects of nitrendipine on capacity of calcium binding of erythrocyte membrane
      and total intraerythrocyte calcium content in SHR rats.
AB  - AIM: To study the effect of nitrendipine (Nit) on the capacity of calcium binding
      of erythrocyte membrane and total intraerythrocyte calcium content in spontaneous
      hypertensive rats (SHR). METHODS: Systolic blood pressure (SBP) of the conscious
      rats was monitored by tailcuff method with a BP and HR recorder for MRS-III rat.
      Erythrocyte membrane was prepared according to modified Bing's method. Calcium
      binding of membrane and total intraerythrocyte calcium content was determined by
      an automatic absorption spectrophotometer. The membrane protein was determined
      with a colorimetric method. RESULTS: Nit (ig 10 mg.kg-1 qd x 20 d) induced a
      significant reduction in total intraerythrocyte calcium content (169 +/- 18 vs 87
      +/- 14 mumol/L cell, P < 0.01) accompanied by a marked fall of SBP (27.1 +/- 2.5
      vs 16.7 +/- 1.0 kPa, P < 0.01) but exerted no influence on the capacity of
      calcium binding of erythrocyte membrane under incubation in CaCl2(0) (basal
      calcium binding) or 40 mmol.L-1 (maximal calcium binding) (21.9 +/- 2.3 vs 22.7
      +/- 2.1 and 55 +/- 14 vs 53 +/- 23 mumol/g protein, respectively, P > 0.05).
      CONCLUSION: The antihypertensive effect of Nit is related to the reduction of
      intracellular calcium and possibly have no direct relation to the capacity of
      calcium binding of cell membrane.

PMID- 8737451
TI  - Effects of dipfluzine on cortical somatosensory evoked potentials and amino acid
      contents in ischemic rat brain.
AB  - AIM: To evaluate the effects of dipfluzine ?1-diphenyl-methyl-4-[3-(4
      fluorobenzoyl)]-piperazine, Dip? on the intra- and extra-cellular contents of the
      amino acids in brain and the cortical somatosensory evoked potentials (SEP) in
      rats with cerebral ischemia. METHODS: Amino acids in micro-dialysates and brain
      tissue homogenates in female Wistar rats with bilateral carotid artery ligation
      (BCAL) were measured by HPLC and SEP was measured by the electrophysiological
      technique. RESULTS: Dip 50 mg.kg-1 i.p. prevented SEP from prolonging of the
      latency and overactivity of lowered amplitude, markedly lowered the elevation in
      extracellular level of glutamate (Glu), aspartate (Asp), and glycine (Gly) in
      intracerebral microdialysates, and alleviated the decrement of intracellular
      contents of Glu, Asp, Gly, taurine (Tau), and GABA in brain tissue. CONCLUSION:
      Dip reduced the disturbance of cortical function and the imbalance between
      excitatory and inhibitory amino acids in ischemic brain, therefore provided a
      further evidence for its protective effect on ischemic cerebral damage.

PMID- 8737452
TI  - Influences of ginsenosides Rb1 and Rg1 on reversible focal brain ischemia in
      rats.
AB  - AIM: To study the influences of ginsenosides Rb1 and Rg1 (active components of
      the total saponins of Panax ginseng) on the brains against ischemia-reperfusion
      injury. METHODS: Rat focal cerebral ischemia was induced by reversible middle
      cerebral artery occlusion (MCAO) without craniectomy. The influences of
      ginsenoside Rb1 and Rg1 on infarct size (IS), neurologic deficit (ND) and the
      contents of calcium and potassium in the infarct were observed. RESULTS: In a 2-h
      ischemia, Rb1 10-40 mg.kg-1 i.v. 30 min before MCAO decreased IS by 20%-49% and
      ND score from 5.1 to 4.1-2.3, and inhibited Ca accumulation and K loss by 22%-50%
      and 18-37%, respectively; Rb1 10-40 mg.kg-1 i.v. immediately after MCA was
      recanalized decreased IS by 12%-35% and ND score from 5.2 to 4.3-3.3, and
      inhibited Ca accumulation and K loss by 10%-40% and 17%-30%, respectively. In
      permanent ischemia, Rb1 40 mg.kg-1 i.v. reduced IS, ND, Ca accumulation and K
      loss. However, Rg1 40 mg.kg-1 i.v. did not show effect on both permanent and 2-h
      MCAO. CONCLUSIONS: Rb1 protected brain from ischemic and reperfusion injuries.

PMID- 8737453
TI  - Cardiovascular effects of injection of argipressin into lateral septal nuclei in
      rats.
AB  - AIM: To determine whether argipressin (Arg) plays a role in central neural
      control of cardiovascular function by acting on the lateral septal nuclei (LSN).
      METHODS: Measuring mean arterial blood pressure (MAP) and heart rate (HR)
      responses followed microinjection of Arg into the LSN of rats anesthetized with
      urethane. RESULTS: Arg (100, 200, and 400 ng) injected into the LSN produced a
      dose-dependent hypertension and tachycardia. Maximal changes of MAP were 0.9 +/-
      0.6, 2.3 +/- 1.3, 4.0 +/- 1.4 kPa, respectively; maximal changes of HR were 12 +/
      27, 50 +/- 33, and 89 +/- 27 bpm, respectively. Pretreatment of the LSN with a
      vasopressin 1 type antagonist d (CH2)5Tyr(Me) Arg abolished the MAP and HR
      responses produced by injection of Arg. Peripheral alpha-adrenergic blockade with
      phentolamine blocked the hypertension responses to injection of Arg into the LSN.
      CONCLUSION: Arg acts in the region of the LSN to exert a central action on the
      cardiovascular system that is mediates by stimulation of sympathetic outflow.

PMID- 8737454
TI  - Toxicity to transferred rat embryos after aspirin treatment during
      preimplantation stage in vivo.
AB  - AIM: To explore the relationship between drug-induced blastopathies and post
      implantation embryotoxicity or developmental defects. METHODS: Pregnant rats on d
      3 were given intragastrically aspirin (0.25, 0.5, and 1 g.kg-1). On d 4, the
      blastocysts were transferred into the uterine horns of pseudopregnant rats (made
      by mating with male rats which had been given intragastrically 3-chloro-1,2
      propanediol 5 mg.kg-1 for 5 d). Uterine contents were examined at term. RESULTS:
      The frequency of blastocysts with morphological alterations (FBMA) was increased
      on d 4 of gestation. The implantation rate was lower than that of the controls. A
      dose-related increase in resorption (55.2%, 69.5%, and 85.2%) and malformation
      rate (3.8%, 44.4%, and 25%), and decrease in viability rate of fetuses (44.8%,
      30.5%, and 14.8%) were observed in test groups with correlations to FBMA.
      CONCLUSION: Embryotoxicity and fetal malformations were induced by treatment of
      aspirin before implantation in a dose-dependent manner.

PMID- 8737455
TI  - Effects of tetrandrine on cytosolic free calcium in cultured rat myocardial
      cells.
AB  - AIM: To study the effects of tetrandrine (Tet) on myocardium. METHODS: Using Fura
      2-AM and AR-CM-MIC cation measurement system, cytosolic free calcium ([Ca2+]i)
      was examined in cultured rat single myocardial cells. RESULTS: The resting
      [Ca2+]i was 90 +/- 12 nmol.L-1 in the presence of Ca2+ 1.3 mmol.L-1 in Hanks'
      solution. Tet 1-100 mumol.L-1 had no effect on the resting [Ca2+]i, but 10-100
      mumol.L-1 depressed the [Ca2+]i elevation when extracellular Ca2+ was 5 mmol.L-1.
      Tet 1-100 mumol.L-1 inhibited KC1 (30 and 60 mmol.L-1) induced [Ca2+]i elevation
      in a concentration-dependent manner, the IC50 value was 8.8 mumol.L-1 (95%
      confidence limits: 3.3-23.7 mumol.L-1) and 6.9 mumol.L-1 (95% confidence limits:
      2.8-17.4 mumol.L-1), respectively. Norepinephrine (NE) 10 mumol.L-1 caused a
      rapid increase in [Ca2+]i in the presence or absence of extracellular Ca2+, Tet
      30-100 mumol.L-1 only decreased the former. Tet 10-100 mumol.L-1 also decreased
      ouabain (Oua)-induced elevation in [Ca2+]i. CONCLUSION: Tet had inhibitory
      effects on Ca2+ transmembrane movement, but it is not a selective calcium channel
      blocker in rat myocardial cells.

PMID- 8737456
TI  - Suberogorgin vs N-cyclohexyl suberogorgamide effects on urine, respiration, and
      blood pressure in rat and cat.
AB  - AIM: To compare the pharmacological actions of suberogorgin (Sub) and N
      cyclohexyl suberogorgamide (N-CS). METHODS: Urine was collected from rats and
      anesthetized cats which had been loaded with water. The concentrations of Na+ and
      K+ in urine were determined in ICAP-9000 atomic emission spectrometry. An
      equitoxic (1/50 LD50) dose of Sub and N-CS was used in cats. RESULTS: The cat
      urine was decreased by 63% after i.v. Sub 0.4 mg.kg-1, but increased by 25% after
      i.v. N-CS 1.5 mg.kg-1, lasting at least 9 h. Sub and N-CS increased the
      respiratory rate and tidal volume, but did not change the blood pressure. The rat
      urine was decreased by 48% after i.p. Sub 1.3 mg.kg-1, but increased by 14% after
      i.p. N-CS 3.2 mg.kg-1. Sub and N-CS increased the concentrations of Na+ and K+ in
      rat urine. These effects lasted at least 24 h. CONCLUSION: Sub is an
      antidiuretic, while N-CS is a diuretic drug.

PMID- 8737457
TI  - Effect of emodin on c-myc proto-oncongen expression in cultured rat mesangial
      cells.
AB  - AIM: To explore the possible molecular mechanism of emodin on the inhibition of
      glomerular mesangial cells (MC). METHODS: In rat MC culture, c-myc mRNA level was
      detected by dot-blotting as expressed by the dilutions of the total RNA on the
      visible dots. RESULTS: Low level c-myc mRNA was found in serum-free cultured
      quiescent MC. Addition of lipopolysaccharide (LPS 10 mg.L-1) induced a higher
      level expression of c-myc mRNA within 30 min, maximal expression at 2.5 h and
      persisted for 6 h. This over-expressing of c-myc mRNA was markedly suppressed by
      emodin (25 mg.L-1), the inhibition of emodin on c-myc mRNA expression was still
      seen at 6 h, and the greatest suppressive effect was at 2.5 h. CONCLUSION: Emodin
      participating in its down-regulatory effect of c-myc mRNA over-expression
      contributes to its inhibitory action on MC.

PMID- 8737458
TI  - Effects of egtazic acid and calcimycin on synthesis of DNA and collagen in
      cultured human lung fibroblasts.
AB  - AIM: To study the effects of egtazic acid (EA) and calcimycin (Cal) on the
      synthesis of DNA and collagen in cultured human lung fibroblasts (HLF). METHODS:
      The synthesis of DNA and collagen was determined by measuring the incorporation
      of [3H]TdR and [3H]proline of HLF respectively. RESULTS: The collagen synthesis
      increased markedly 24 h after exposure to both EA (0.05-4 mmol.L-1) and Cal (0.25
      20 mumol.L-1), and that there was no obvious change in DNA synthesis. After 36-48
      h exposure, both DNA and collagen syntheses decreased in the groups of EA (1, 2,
      and 4 mmol.L-1); the DNA synthesis was also suppressed in Cal groups in a
      concentration-dependent manner, whereas collagen synthesis decreased only in Cal
      (10 and 20 mumol.L-1). CONCLUSION: Extracellular Ca2+ influx into fibroblasts
      increased collagen production, However, the DNA synthesis was suppressed when the
      cytosolic Ca2+ was too high or too low.

PMID- 8737459
TI  - [Comparison between kinetics of positive inotropism of ibopamine and ouabain].
AB  - AIM: To compare the kinetics of positive inotropism between ibopamine (Ibo) and
      ouabain (Oua). METHODS: The isolated right papillary muscle of cat was used to
      assess the positive inotropic effects by cummulative concentrations of Ibo and
      Oua. The maximal effects was recognized as the contraction just before the
      appearance of spontaneous contraction. A Hill equation was developed by using lg
      [E/(Emax-E)] vs lg C. RESULTS: The S value of Ibo was smaller than that of Oua,
      causing C95/C5 (ratio of concentrations producing 95%/5% of Emax) of Ibo (264)
      elevenfold as large as Oua (22.9). Comparing with Oua, concentrations of Ibo
      initiating effects were lower, the slope was smaller, and higher concentrations
      were required for producing maximal effect. During drug concentration declining,
      the effect-concentration curve of Ibo showed a counter-hysteresis loop, more
      remarkable than Oua. CONCLUSION: The changes in positive inotropism of Ibo
      against drug concentrations were less than those of Oua.

PMID- 8737460
TI  - [Synergism of sobuzoxane in combination with doxorubicin against leukemia P388 in
      mice].
AB  - AIM: To study the antitumor activity of sobuzoxane (Sob) in combination with
      doxorubicin (Dox) and the effect of Sob on Dox-induced cardiotoxicity. METHODS:
      DBA/2 mice bearing transplanted leukemia P388 were given i.v. Dox 2 mg.kg-1.d-1
      for 3 d, 4 mg.kg-1.d-1 for 1 d combined with ig Sob 20, 40 mg.kg-1.d-1 for 7 d.
      The increase in life span (ILS) of each group was recorded in 30 d. The
      myocardium of moribund mice was examined by transmission electron microscopy.
      RESULTS: The ILS of combination therapeutic groups of Sob with Dox was 48.7%,
      57.3%, 59.0%, and 62.4% respectively, which were 30%-90% higher than the sum of
      ILS of two groups treated with Dox and Sob separately (P < 0.01). The
      ultrastructural injury of cardiomyocytes of P388-bearing mice caused by
      combination chemotherapy with Dox plus Sob was markedly attenuated compared with
      Dox alone. CONCLUSION: Sob with Dox exhibited an antitumor synergistic effect on
      leukemia P388, and the cardiotoxicity of Dox was reduced by Sob.

PMID- 8737461
TI  - [Effects of aspirin and nifedipine alone or in combination on hemodynamics in
      anesthetized dogs].
AB  - AIM: To study the effects of the combination of aspirin (Asp) and nifedipine
      (Nif) on hemodynamics in 8 anesthetized dogs. METHODS: Tension time index (TTI),
      left ventricular work index (LVWI), mean arterial pressure (MAP), and total
      peripheral vascular resistance (TPVR), femoral artery blood flow (FBF),
      ventricular systolic pressure (LVSP), maximum of its first derivative
      (dp/dt(max)), left ventricular end diastolic pressure (LVEDP) and heart rate (HR)
      were recorded on polygraph and electromagnetic flowmeter. RESULTS: Asp 5, 10
      mg.kg-1, i.v. exerted a significant effect on the hemodynamic indices, wheras Nif
      15 micrograms.kg-1, i.v. decreased TTI, LVWI, MAP, and TRVR, increased FBF
      distinctively, and slightly affected LVSP, dp/dt(max), LVEDP, and HR. The effects
      of Asp in combination with Nif on hemodynamics were similar to those of Nif
      alone. CONCLUSION: The improvement of cardiovascular function caused by Nif was
      not affected by the presence of Asp.

PMID- 8737462
TI  - [Proceedings of the 3rd international symposium on ion channels and Ca2+
      antagonists].

PMID- 8737463
TI  - [Prospects for application of molecular biotechnique to pharmacognosy].

PMID- 8737464
TI  - [Medicinal plant resources of Berberis L. in Guizhou province].
AB  - Based on field investigation and identification of 19 species and one variety of
      medicinal plant of Berberis produced in Guizhou Province, it has been found out
      that among these species 3 is found to be new ,4 species and one variety are
      discovered for the first time in Guizhou province. Geographical distribution,
      perpendicular distribution and medicinal uses of these species are spelled out
      and a key for their identification is given.

PMID- 8737465
TI  - [A comparative study on the chemical constituents of cultivated and wild fructus
      Gardeniae].
AB  - Studies have been made on the preliminary tests of the chemical constituents of
      cultivated and wild Fructus Gardeniae on the comparative analysis of the thin
      layer chromatograms, IR and UV spectra of 95% ethanolic extracts as well as
      extracts obtained with four different solvents, and on the content determination
      of gardenosides. The results reveal that the cultivated and wild Fructus
      Gardeniae have similar chemical constituents, but differ in the contents of some
      constituents.

PMID- 8737466
TI  - [A preliminary study on essential oils for the control of Ustilago coicis].

PMID- 8737467
TI  - [Effect of ginger-processing on beta-sitosterol and total alkaloid contents in
      Rhizoma Pinelliae].
AB  - The contents of beta-sitosterol of five processed products of Rhizoma Pinelliae
      we were determined by TLC. The result showed that the lowest content of beta
      sitosterol was found in Rhizoma Pinelliae boiled with ginger juice (0.0180%), and
      the highest in raw Phizoma Panelliae (0.0572%). The contents of total alkaloid of
      five processed products of Phizoma Pinelliae were also determined by gravimetry
      and spectrophotometry with acid dye. The result showed that the highest content
      of total alkaloid was obtained in Rhizoma Pinelliae boiled with ginger juice and
      alum, and the lowest in Rhizoma Pinelliae boiled with ginger juice.

PMID- 8737468
TI  - [Investigation and experimental study on the standards and quality of leech
      pieces].
AB  - It has been confirmed by investigation that Whitmania pigra is the main medicinal
      breed of leech, and filiform pieces are the best for extraction. The quality of
      leech processed by 3 different methods has been studied qualitatively and
      quantitatively in terms of amounts of extraction, TLC, electrophoresis of protein
      and anti-thrombin action.

PMID- 8737469
TI  - [Exploration on oral preparations of Chinese materia medica by semi-bionic
      extraction].
AB  - In the light of biopharmacy, the present new technology to extract oral
      preparations of Chinese traditional medicinal by semi-bionic method was designed.
      In the technological process, the prescribed drugs were decoction and extracted
      first in an acid solution with a certain value and then in an alkaline solution
      with ther pH value. Afterwards, the extracts were filtered concentrated, dried
      and made into preparation. The theoretical basis of this technology was analysed
      and the concrete procedures were introduced, with Shaaogan Zhitong pill as an
      example.

PMID- 8737470
TI  - [Effect of ultrasonic extraction on extraction rate of berberine].
AB  - The parameters are proposed which can be used in extracting berberine from the
      rhizoma of Coptis chinensis with ultrasound. Compared with traditional immersing
      method, ultrasonic extraction is time saving and of higher extraction rate.

PMID- 8737471
TI  - [Hydrothobic constituents of Nyssa sinensis Oliv].

PMID- 8737472
TI  - [Chemical constituents of Cyclocarya paliurus (Batal.) Iljinsk].
AB  - Four compounds were isolated from the leaves of Cyclocarya paliurus. They were
      identified as daucosstero, beta-L-arabopyranose, steraric acid and palmitic acid
      on the basis of spectral data and chemical properties. All of them were isolated
      from this plant for the first time.

PMID- 8737473
TI  - [Determination of bakuchiol in the fruit of Psoralea corylifolia L].
AB  - A GC method for the determination of bakuchiol of described. GC conditions for
      analysing are as follows: stationary phase: SE-30: injector temperature: 250
      degrees C: column temperature: 200 degrees C and detector: FID. The linear range
      of this method is 0.24-2.4 micrograms and the average recovery is 98.82%, with a
      relative standard deviation of 1.58%. This method has been successfully used to
      determine the content of bakuchiol in the samples on the market in 11 different
      areas, the contents being 1%-7%.

PMID- 8737474
TI  - [Effects of buyang huan wu decoction on rat hyperlipemia model].
AB  - Buyang Huan Wu Decoction can obviously lower the blood-lipid in rat hyperlipemia
      model, as well as drop the cholesterol in the aortic wall. Moreover, the
      decoction can drop the rising specific viscosity of blood and plasma, raise SOD
      and lower LPO in the blood.

PMID- 8737475
TI  - [Active antisenile constituents in Cistanche deserticola Y. C. Ma].
AB  - From the dry bulbs of Cistanche deserticola a branch of orobahchacease plant
      growing in Inner Mongolia two active antisenile constituents (D-mannitol and
      polysaccharide) were isolated and identified. Chemical analysis and spectroscopic
      tests show that D-mannitol corresponds to the authentic standard, and
      polysaccharide is condensed from rhamnose, xylose, arabinose and galactose.

PMID- 8737476
TI  - [In vitro experiment on scavenging oxy-radical and suppressing myocardial lipid
      peroxidation with sini decoction].
AB  - Results indicate that Sini Decoction has a significant effect of anti-lipid
      peroxidation of its components, Radix Aconiti Preparata and Radix Glycyrrhizae
      can significantly suppress lipid peroxidation of myocardial homogenate, while
      Rhizoma Zingiberis cannot. The decoction can effectively scavenge oxygen free
      radicals, each component having similar effect to some extent.

PMID- 8737477
TI  - [Effect of plant polysaccharides on phosphatidylinositol turnover of sarcoma S180
      cell membranes].
AB  - Mice sarcoma S180 cell membranes, [r-32 P]ATP and plant polysaccharides (PPS,
      ASPS, TF and lentinan) were incubated together for 5 min at 30 degrees C.
      Phosphatidylinositides were isolated and subjected to scintillation fluid
      counting. The results showed that PPS and ASPS, especially the latter, could
      inhibit the phosphatidylinositol turnover obviously, while TF and lentinan had no
      such effect.

PMID- 8737478
TI  - [Relation between 5 flavors and channel tropism in some traditional Chinese
      drugs].
AB  - In the present paper, the relationship between five flavors and channel tropism
      is statistically studied for 261 traditional Chinese drugs which are reported to
      have only on flavor in the Chinese Pharmacopeia (1990 edition). The results show
      that in attribution there are considerable differences between the law of bitter
      and the law of acrid, between the law of sweet and law of salty, and between the
      law of acrid and the law of salty, while the laws of other pairs of flavors are
      similar. The laws of channel tropism are considerably affected by the mergence of
      exterior and interior channels. The relationship between five flavors and channel
      tropism is thus widely divergent from that held by the traditional theory of five
      elements.

PMID- 8737479
TI  - Characteristics of cyclicity in maiden thoroughbred mares in the United Kingdom.
AB  - The characteristics of the cyclicity of 12 maiden thoroughbred mares kept in two
      groups were studied over a total of 58 cycles. On average, oestrus lasted 5.3
      days and in 60 per cent of the cycles ovulation occurred in the last two days of
      oestrus. Oestrus and ovulation tended to be synchronised in each group of mares.
      The mean diameter of single-ovulating preovulatory follicles on the day before
      ovulation was 41.5 mm and during the seven days before ovulation they grew 2.5
      mm/day. More than one follicle ovulated in 19 (33 per cent) of the cycles (seven
      double ovulations and 12 dioestrous ovulations). All the oestrous mares and 25
      per cent of the mares with dioestrous ovulations had uterine oedema on the day
      before ovulation.

PMID- 8737480
TI  - Plasma lipase concentration as an aid to the early detection of pancreas disease
      in farmed Atlantic salmon (Salmo salar).
AB  - Plasma lipase concentrations were determined in Atlantic salmon post smolts at
      weekly intervals on two farms from late June. On one farm there was a significant
      increase (P < 0.001) in lipase concentration which coincided with a suspicion of
      pancreas disease on clinical grounds. A definitive diagnosis was subsequently
      confirmed by histopathology. The exercise was repeated on 10 farms in the
      following year and the results provided additional evidence of the value of
      monitoring lipase concentration as an indication of pacreas disease at an earlier
      stage than it can be detected by clinical signs and histopathology alone.

PMID- 8737481
TI  - Factors affecting the mortality of lambs in transit to or in lairage at a
      slaughterhouse, and reasons for carcase condemnations.
AB  - The computerised records of all the lambs slaughtered at one plant from August
      1991 to July 1992 were used to determine the mortality rate throughout the year
      and to examine the variables that could have been associated with changes in the
      mortality rate. The plant processed 3.3 per cent of all the lambs that were
      slaughtered in the United Kingdom during the period. Lambs arriving for slaughter
      from a livestock auction were over four times more likely to die in lairage, or
      to have died during transport, than lambs which were sent directly from the farm.
      However, the overall mortality rate was only 0.0182 per cent and lower than that
      for other species for which figures were available. Changes in the mortality rate
      of the lambs from livestock auctions appeared to be associated with the price of
      slaughter lambs, and periods of increased mortality coincided with increased
      rates of carcase condemnations due to 'arthritis', 'abscess' and 'pleurisy'.

PMID- 8737482
TI  - The interval between birth and sternal recumbency as an objective measure of the
      vitality of newborn calves.
AB  - The time from birth to attaining sternal recumbency (T-SR) was recorded for 219
      newborn calves in order to evaluate its use as a parameter for diagnosing
      vitality. Calves were defined as vital if they received routine care without
      medical treatment and survived seven days from birth without any symptom of
      illness (n = 192). Those which did not fulfil these conditions were categorised
      as non-vital (n = 27). Ten calves were born spontaneously and the others were
      delivered either by caesarean section (n = 105), normal extraction (n = 78) or
      forced extraction (n = 26). The mean (+/- sd) T-SR values of the vital calves in
      these delivery groups were: 4.0 +/- 2.2, 4.5 +/- 3.1, 5.4 +/- 3.3 and 9.0 +/- 3.3
      minutes, respectively. Jugular blood gas and pH measurements were performed at
      several fixed times after birth until pH and base excess had reached values of
      over 7.2 and more than -5.0 mmol/litre, respectively. Mean pH and base excess
      values of vital calves 10 minutes post partum were significantly higher and
      lower, respectively, than those of non-vital calves. Forcefully extracted calves
      had longer T-SR, more serious acidosis, recovered more slowly from acidosis, died
      more, and exhibited trauma more frequently. A T-SR of at least 15 minutes had a
      predictive value of 84 per cent for non-vitality, while 10 minute pH values of
      less than 6.9 had a lower predictive value, namely 68 per cent, for non-vitality.
      Correlations between T-SR values and 10 minute pH and base excess values were
      moderate, whereas correlations between T-SR values and PCO2 values were weaker
      still and much more dependent on the type of delivery. It is concluded that T-SR
      determination is a valuable, practicable and objective diagnostic tool for
      estimating the condition of newborn calves during the first 15 minutes of life.
      The diagnostic value of a single pH measurement on the jugular blood of a
      neonatal calf is doubtful.

PMID- 8737483
TI  - Observations on the pathogenesis of digital dermatitis in cattle.

PMID- 8737486
TI  - Embryonic and fetal mortality in cattle.

PMID- 8737484
TI  - Organophosphorus sheep dips.

PMID- 8737488
TI  - Salmonella enteritidis in eggs stored at room temperature.

PMID- 8737487
TI  - Sample preparation for M paratuberculosis polymerase chain reaction in faeces and
      tissues.

PMID- 8737489
TI  - A comparison of the haemagglutinating and enzymic activities of Bacteroides
      fragilis whole cells and outer membrane vesicles.
AB  - The haemagglutinating and enzymic activities of the obligately anaerobic
      pathogenic bacterium Bacteroides fragilis were examined. Outer membrane vesicles
      are released from the surface of B. fragilis. They can be detected by electron
      microscopy in ultrathin sections and bacterial suspensions after negative
      staining. Electron microscopy and immunogold labelling with a MAb specific for
      surface polysaccharide of B. fragilis confirmed that the vesicles carried outer
      membrane associated epitopes. The haemagglutinating activity of whole cells from
      populations of B. fragilis strains NCTC9343, BE3 and LS66 enriched by Percoll
      density gradient centrifugation for a large capsule (LC), electron dense layer
      (EDL); non-capsulate by light microscopy) and outer membrane vesicles (OMV) which
      had been purified by centrifugation from EDL-enriched populations were compared
      using human and horse erythrocytes. The enzymic activity of OMV, LC- and EDL
      enriched populations, as detected by the API ZYM kit, was compared for strains
      NCTC 9343 and BE3. Purified OMV from the strains examined exhibited both
      haemagglutinating and enzymatic activity. Haemagglutination by the EDL-enriched
      population was sensitive to treatment with sodium periodate. The LC-enriched
      population haemagglutinated only after ultrasonic removal of the capsule. This
      indicates that the LC masks a haemagglutinin. The results suggest a potential
      role for OMV in the virulence of B. fragilis.

PMID- 8737491
TI  - Streptococcus pyogenes infection in mice.
AB  - We inoculated 5 to 7-week-old female C3HeB/FeJ mice with Streptococcus pyogenes
      strain B514-Sm (type M50) by both an intranasal and intratracheal route and
      characterized the resulting illness. Following intranasal inoculation, the
      animals developed signs of illness within 1 to 8 days post-inoculation which
      correlated with acute, suppurative, bronchopneumonia during histopathologic
      analysis; however, the relationship of response to dose was non-linear, as seen
      previously in a small group of mice. Intratracheal inoculations were then
      performed to increase the quantitative reliability of the model. Following
      intratracheal inoculation, the animals succumbed to an illness that was
      indistinguishable from that seen after intranasal inoculation, and the incidence
      of pneumonia followed a steep dose response curve. The dose at which 50% of the
      animals exhibited signs of respiratory illness within 72 h was 1.0 x 10(7) colony
      forming units. All of the animals that appeared ill had lung lesions as
      determined by gross and histopathologic examination. Bacteraemia followed
      pneumonia in two-thirds of the intratracheally inoculated animals, indicating
      that the S. pyogenes had crossed tissue barriers. We hope that this model will be
      useful in future studies concerning the role of suspected streptococcal virulence
      factors in the later stages of pathogenesis of invasive S. pyogenes infection.

PMID- 8737490
TI  - Molecular cloning and expression of bovine interleukin-8.
AB  - Interleukin-8 (IL-8) is a neutrophil and T-lymphocyte chemotactic and activating
      factor. This cytokine is produced by many cell types including macrophages in
      response to a variety of microbial and non-microbial agents. In the present
      study, we determined the nucleotide sequence for bovine IL-8 cDNA. The amino acid
      sequence encoded by this cDNA shares 76 and 87% homology with the human and swine
      IL-8 proteins, respectively. Bovine IL-8 cDNA was expressed in Escherichia coli
      as a beta-galactosidase fusion protein. Western blotting demonstrates that this
      fusion protein, but not beta-galactosidase cross-reacts with monospecific anti
      human IL-8 antiserum. We also studied the induction of IL-8 mRNA synthesis in
      bovine alveolar macrophages (BAM) stimulated with heat-killed Pasteurella
      haemolytica. IL-8 mRNA was induced in BAM as early as 1 h and was detectable at
      high levels 12 h post-stimulation with P. haemolytica. A dose titration of P.
      haemolytica and E. coli endotoxins showed that a relatively low level of P.
      haemolytica endotoxin induced high levels of bovine IL-8 mRNA. The significance
      of these findings in the pathogenesis of bovine pneumonia caused by P.
      haemolytica is discussed.

PMID- 8737492
TI  - Deletion and reintroduction of glucosyltransferase genes of Streptococcus mutans
      and role of their gene products in sucrose dependent cellular adherence.
AB  - Streptococcus mutans has three kinds of glucosyltransferases (GTases), i.e. GTase
      I, GTase-SI and GTase-S. These enzymes co-operatively synthesize adhesive glucan
      from sucrose, which contributes to firm adherence of growing organisms to solid
      surfaces. In this study, the genes encoding GTase-I (gtfB) and GTase-SI (gtfC) of
      S. mutans MT8148 (serotype c) were inactivated by the insertion mutagenesis by
      allelic exchange. Three types of isogenic mutants lacking either GTase-I, GTase
      SI or both, respectively were isolated. Sucrose dependent cellular adherence of
      these mutants were significantly lower than that of the parent. Adherence of
      GTase-SI deficient mutant was lower than that of GTase-I deficient mutant. We
      then generated Escherichia coli-Streptococcus shuttle vectors carrying the gtfB
      and gtfC gene. The shuttle vector containing the gtfB gene was transformed into
      the GTase-I deficient mutant. Western blot analysis of the transformant revealed
      that GTase-I protein was fully expressed. Sucrose dependent adherence of the
      transformant increased but did not reach that of the parent. Similarly, the
      shuttle vector containing the gtfC gene was transformed into the GTase-SI
      deficient mutant. The expression of GTase-SI and sucrose dependent adherence of
      the transformant was revealed to be at a level similar to those by the parent.
      These results indicated that GTase-SI does play an essential role in the
      production of adhesive glucan that can lead to firm cellular adherence to solid
      surfaces.

PMID- 8737493
TI  - Studies into the role of the SEF14 fimbrial antigen in the pathogenesis of
      Salmonella enteritidis.
AB  - To investigate the role of the SEF14 fimbrial antigen in pathogenesis, a single
      defined sefA (SEF14-) inactivated mutant of Salmonella enteritidis strain LA5 was
      constructed and tested in a number of biological assay systems. There was no
      significant difference between the wild-type strain and the isogenic SEF14-
      mutant in their abilities to adhere to and invade HEp-2 epithelial cells or their
      survival in mouse peritoneal macrophages, whereas the SEF14- mutant was ingested
      more rapidly by isolated human PMN. Both the strains colonized the intestine,
      invaded and spread systemically in 1 day-old chicks, laying hens and BALB/c mice
      equally well. A significantly greater number of chicks excreted the wild-type
      SEF14+ strain during the first week following infection as compared to those
      infected with the SEF14- mutant. However, similar numbers of chicks excreted the
      two strains between 2 and 7 weeks after infection. These results indicate that
      possession of SEF14 fimbriae alone do not appear to play a significant role in
      the pathogenesis of S. enteritidis although its contribution to virulence may be
      dependent on the host species infected.

PMID- 8737494
TI  - Comparison of the infectivity of isolates of Listeria monocytogenes following
      intragastric and intravenous inoculation in mice.
AB  - The infectivity of 19 haemolytic isolates of Listeria monocytogenes from
      different sources (clinical and environmental) and representative isolates from
      Listeria ivanovii and Listeria innocua was compared following intragastric (i.g.)
      and intravenous (i.v.) inoculation in immunocompetent male BALB/c mice. There was
      marked variation in the infectivity of the different isolates by either route but
      when isolates were ranked in descending order by spleen count, following i.g.
      administration, the strains fell into four groups. Infectivity of some isolates
      also differed when i.v. inoculation was compared with i.g. administration, so
      that assessment of virulence by spleen counts only following i.v. inoculation
      might fail to detect isolates of poor infectivity by the i.g. route. These
      results suggest that intragastric inoculation of normal immunocompetent mice is a
      useful model for detecting strains of L. monocytogenes that are poorly invasive
      via the gut even though they are relatively virulent by intravenous inoculation.

PMID- 8737495
TI  - [What should be done for diarrhea during antibiotic therapy?].

PMID- 8737496
TI  - [Prognostic factors of surgically treated colorectal cancer].

PMID- 8737497
TI  - [Treatment of rectal hemorrhage secondary to radiation proctitis].

PMID- 8737498
TI  - [What is the medical therapeutic approach to gastroesophageal reflux?].

PMID- 8737499
TI  - [The laser in digestive surgery].

PMID- 8737501
TI  - [Imaging of the recurrence of colorectal cancer].

PMID- 8737500
TI  - [Ileo-anal anastomosis in Crohn disease].

PMID- 8737502
TI  - [Drug-induced intestinal complications].

PMID- 8737503
TI  - [Treatment of chronic viral hepatitis].

PMID- 8737504
TI  - [Chronic idiopathic constipation in adults. Pathogenesis and treatment].
AB  - The purpose of this review article is to outline the main factors underlying
      adult chronic idiopathic constipation (colic substrates, bacterial fermentation,
      colic peristalsis, perineal anomalies and psychological factors) as well as
      readily available exploratory methods (colic transit time, anorectal manometry).
      A review is made of the various therapeutic possibilities, taking into account
      hygienico-dietetic and pharmacological treatments (mono- or multifactorial
      laxatives), biofeedback and psychological approaches. The main cases seen in
      clinical practice are described.

PMID- 8737505
TI  - [Infectious diarrhea. Which germ? Which treatment?].

PMID- 8737506
TI  - [Medical treatment of gastroesophageal reflux in adults].

PMID- 8737507
TI  - [The application of cholangio-MRI in the examination of the biliary tree].

PMID- 8737508
TI  - [Endoscopic treatment of superficial digestive cancer].

PMID- 8737509
TI  - [Hemochromatosis, Wilson's disease. Some diseases which are not often
      considered].

PMID- 8737510
TI  - [The mechanism of action of sennosides].
AB  - A review of the recent progress in the study of the mode of action of the
      sennosides, the active constituents of the senna drug, is presented. An
      interaction between rhein anthrone, the active metabolite of the sennosides, and
      the immune cells of the colon is suggested as a base for laxative activity.

PMID- 8737511
TI  - [Counseling male adolescents with homosexual orientation and their parents].
AB  - In counseling of adolescents with a homosexual orientation and their parents we
      are not only confronted with the typical conflicts of this developmental phase as
      those between autonomy and dependence. Moreover we are concerned with specific
      problems which--because of the coming out--result for the adolescent himself as
      well as for the whole family system. It is important in such counseling that the
      following three questions are considered: the characteristic tendencies of
      separation of the adolescent and the parental reactions to it, the parental
      acceptance of the homosexual orientation of their son, and the coming out process
      for the adolescent and the family as a whole.

PMID- 8737512
TI  - [Child and adolescent psychiatry and child and adolescent welfare: general
      interprofessional relations--results of a study].
AB  - Child and adolescent Psychiatry on the one hand and Social Welfare Services and
      Child Protection on the other share common fields. The theoretical orientation of
      the Social Sciences differs from that of Psychiatric Medicine, producing a
      potential of conflict in areas of mutual operation. This report is based on an
      analysis of the transferrals from Child and adolescent psychiatric in-patient
      treatment to foster care. The results show that the children concerned mainly
      present with conduct disorder plus emotional problems and that the process of
      transferral is impaired by a number of factors which can be clearly named.

PMID- 8737513
TI  - [Bibliotherapeutic dream work after acute psychotic decompensation].
AB  - The paper reports about a follow-up treatment of a 15,5 year old female youth,
      who had suffered a polymorph psychotic disturbance with schizophrenic
      symptomatology. The symptoms began after a sexual encounter with a friend. During
      her illness the patient considered herself as "Jesus". By means of intensive
      dream work and bibliotherapy the psychotic events could be identified and
      understood subjectively. Three months after the onset of the illness the
      psychotic anxieties could be addressed by reading the Grimm fairy tale "The
      robber's bride" and could thus be better understood and classified. The patient's
      anxieties referred to physical and emotional disintegration (to be incorporated,
      to be Christ himself, and to give away his body). The patient could recall these
      anxieties as having actually occurred to her at the beginning of her illness.

PMID- 8737514
TI  - [Viewing of horror and violence videos by adolescence. A study of speech samples
      of video consumers with the Gottschalk-Gleser Speech Content analysis].
AB  - In 1990 pupils of different schools in Wurttemberg were interviewed about their
      television and video consumption. It turned out that a high percentage of mainly
      male pupils of Hauptschulen (upper division of elementary schools) and special
      schools excessively and regularly consumed films which were on the index (X
      rated) or seized depicting horror and violence. Subsequent to the inquiry through
      questionnaires and different personality tests, speech samples of 51 test persons
      were recorded on tape. 5 speech samples had to be excluded from further
      investigation since they contained less than 70 words. The transcribed and
      anonymized records were examined according to the Gottschalk-Gleser content
      analysis of verbal behavior, and two groups of so-called seldom lookers (n = 22)
      and frequent lookers (n = 24) were compared to each other. The frequent lookers
      significantly often reported about film contents which presumably means that
      their imagination is more restricted and less productive than that of the other
      group. In addition, this group of frequent lookers had significantly higher
      scores concerning death anxiety and guilt anxiety. With regard to hostility
      affects, their scores were also significantly raised concerning outward-overt
      hostility, outward-covert hostility, and ambivalent hostility. Probably the group
      of frequent lookers comprised more test persons with relationship disorders, with
      borderline risks, dissocial personality features, and problems to cope with their
      aggressiveness. So they show on the one hand a raised affinity to watch such
      films, but simultaneously unconscious and conscious learning processes take place
      which stimulate further aggressive fantasies (and possibly also actions).

PMID- 8737515
TI  - [The "hidden" indication].

PMID- 8737516
TI  - [Primary therapy of advanced ovarian carcinoma: current status and perspectives].
AB  - Standard therapy of advanced ovarian cancer includes staging laparotomy with
      aggressive debulking, possibly pelvic and para-aortic lymphadenectomy, and
      postoperative chemotherapy. Until present, combination chemotherapy with cis
      /carboplatin and cyclophosphamide has been standard. Due to the positive results
      emerging from recent clinical trials, paclitaxel in combination with platinum
      might soon emerge as a new standard for patients with advanced ovarian cancer.
      The role of high-dose chemotherapy is currently under investigation.
      Pretherapeutic chemosensitivity testing, using a third-generation assay, is
      studied in randomized trials. Since the cost/benefit ratio is increasingly
      playing an important role, a cost comparison of the six most commonly used
      chemotherapy protocols is presented.

PMID- 8737517
TI  - [Diagnostic value of combined vaginal ultrasound and hysteroscopy in peri- and
      postmenopausal bleeding].
AB  - OBJECTIVE: Is it possible to reduce the rate of curettages by using ultrasound
      and hysteroscopy? METHODS: Transvaginal sonography, hysteroscopy, and dilation
      and curettage were performed in 103 patients with menometrorrhagia or
      postmenopausal bleeding. The patients were divided into three groups, depending
      on the ultrasound findings. RESULTS: All 9 cases with cancer of the endometrium
      were found in group 3. 1 of the 9 carcinomas was not detected by hysteroscopy.
      CONCLUSIONS: We believe that dilation and curettage is necessary in symptomatic
      women with an endometrial thickness < 4 as well as > 4 mm. Prospective studies
      have to clear the question of whether endometrial carcinomas can be detected by
      hysteroscopy in cases with an endometrium < 4 mm thick.

PMID- 8737518
TI  - [Value of ultrasound in early detection of endometrial carcinoma].
AB  - OBJECTIVE: The purpose of our study was to examine the diagnostic value of the
      biometry of the endometrium for the early detection of endometrial carcinomas in
      postmenopausal women as well as to compare our results with those of other
      authors. METHODS: In 69 post menopausal women the endometrial thickness measured
      by vaginosonography before diagnostic curettage or hysterectomy was compared with
      the histological results. RESULTS: Using a cutoff value of 6 mm, a sensitivity of
      96%, a specificity of 24%, a positive predictive value of 16%, and a negative
      predictive value of 97% were established. CONCLUSIONS: Endovaginal ultrasound
      evaluation of the endometrial thickness is not specific enough to be used
      screening method for the early detection of endometrial carcinoma.

PMID- 8737519
TI  - [Ultrasound morphologic evaluation of the postmenopausal endometrium. A
      prospective study].
AB  - OBJECTIVE: The measurement of the endometrial thickness by means of transvaginal
      sonography has been discussed as a tool for cancer screening. The aim of the
      study was to evaluate such a sonomorphological characterization of the
      endometrium performed by physicians in training. METHODS: A transvaginal
      sonography was performed in 400 patients before histological examination
      (dilatation and curettage or hysterectomy). The endometrial thickness measured as
      double layer and the sonographic patterns were determined. RESULTS: The
      endometrial thickness correlated with the histological findings: the median
      thickness was 6 mm for the normal endometrium and increased to 9 mm for
      polypiform hyperplasias 9.5 for cervical mucous polyps, and to 14 mm for
      glandular-cystic hyperplasias and carcinomas (p < 0.001 vs. normal). The
      sonomorphological grading score was also associated with the histology. For the
      sonomorphological grading, the sensitivity decreased to 80%, but the specificity
      increased to 62%. CONCLUSIONS: The sonomorphological pattern is superior to the
      sole determination of the endometrial thickness. This method is practicable under
      routine conditions performed by physicians in training. However, the specificity
      of both methods is too low to recommend them for cancer screening.

PMID- 8737520
TI  - [Beta-thalassemia and pregnancy: 2 rare cases].
AB  - Our experience of beta-thalassemia during pregnancy is limited to 2 rare cases.
      The first patient suffered from beta(0)/beta(+) thalassemia, and therapy
      consisted of 300 ml of concentrated red cells every month and deferoxamine.
      During pregnancy the patient received 300 ml of concentrated red cells every
      week, and a healthy child was born by cesarean section. The second patient
      suffered from Cooley's disease till 1985. She received many transfusions but was
      allergic to deferoxamine. Later, bone marrow transplantation was successful. Her
      normal full-term pregnancy concluded with the birth of a healthy child.

PMID- 8737521
TI  - [Recommendations of the Urogynecology Study Group on ultrasound of the lower
      urinary tract within the scope of functional urogynecologic diagnosis].

PMID- 8737522
TI  - [Risk and prevention of thromboembolism complications in gynecologic
      malignancies].
AB  - Gynecologic malignancies are often associated with deep vein thrombosis and
      pulmonary embolism, even before treatment is begun. But such complications also
      happen during treatment, also if thromboembolism prophylaxis is performed. The
      incidence of pulmonary embolism before treatment was investigated using
      scintigraphy. In a retrospective and in a prospective randomized trial, various
      methods of thromboembolism prophylaxis were evaluated during primary or
      postoperative radiation therapy. Pulmonary embolism was present in 11.9% of the
      patients admitted with uterine malignancy. Retrospectively, there were deep vein
      thromboses in 6.8%, pulmonary embolisms in 3.8% and bleeding complications in
      5.3% of the patients receiving thromboembolism prophylaxis with acenocoumarol
      during radiation therapy of cervical and endometrial cancer. In the prospective
      study, deep vein thromboses occurred in 1.5%, pulmonary embolisms in 5.9% and
      bleedings in 2.2%, with both the LMW heparin and the acenocoumarol groups
      presenting similar results. Thromboembolism is a frequent paraneoplasia of
      uterine malignancies. The prevention of thromboembolic complications during
      radiation therapy of uterine malignancies is efficacious and safe using either
      LMW heparin or acenocoumarol.

PMID- 8737523
TI  - [Overexpression of p53 as prognosis factor in vulvar carcinoma].
AB  - Twenty-five cases of squamous cell carcinoma of the vulva were examined for p53
      protein overexpression using immunohistochemistry. p 53 protein overexpression
      was associated with poorer overall survival.

PMID- 8737524
TI  - [Early invasive cervix carcinoma--FIGO 1994].
AB  - 7078 histological cases of cold-knife conisation have been reevaluated. Because
      of the changes of the FIGO 1994 staging system, all microinvasive cancers in that
      material have been reclassified. This had major histomorphological and clinical
      consequences.

PMID- 8737525
TI  - [Immunostimulating protein 90K in ovarian carcinoma].
AB  - Protein 90K is a tumor-associated antigen, which is able to enhance the cytotoxic
      activity in lymphokine-activated and natural killer cells as well as the IL-2
      release in peripheral blood lymphocytes. In our in vitro experiences we observed
      a stimulatory effect by IFN-alpha and IFN-gamma on 90K-specific mRNA expression
      and protein release in ovarian cancer cells, and 90K was furthermore found to be
      a potent stimulator of macrophage activity. Protein 90K seems to be involved in
      tumor immunology; it may represent a critical link between tumor and immune
      system.

PMID- 8737526
TI  - [Computer-assisted analysis of ultrasound sequences of the left ventricle for
      determining ejection fraction].
AB  - The present study describes an automatic procedure for calculating the ejection
      fraction on the basis of ultrasound images. This procedure is divided into three
      steps, and programmed in C/UNIX. In an initial step, an algorithm, known as
      sequence analysis, is used to identify the enddiastolic and endsystolic images
      from a series of ultrasound images. With the use of a template matching procedure
      for calculating displacement vectors, a method has been developed for the first
      time for analysing moving images for identification purposes. The subsequent
      image analysis employs various filter processes for noise suppression, contrast
      enhancement, image sharpening, edge detection and segmentation. On the basis of
      the geometrical data of the segmented left ventricle obtained in this way the
      respective volumes and ejection fraction are calculated. To validate this
      automatic procedure, the series of ultrasound images were examined by a
      cardiologist. It was found that the identification of the endsystolic and
      enddiastolic image was correct, and that there was good agreement between the
      automatically determined and manually determined ejection fraction.

PMID- 8737527
TI  - [Modeling vestibulo-ocular reflexes in everyday activities].
AB  - Fundamental data for the establishment of a new clinical testing procedure for
      patients suffering from equilibrium disorders were developed. A mathematical
      model that predicts vestibulo-ocular reflex responses (eye velocities) to three
      dimensional head movements was investigated. An experimental set-up permitting
      the simultaneous recording of the head and eye movements was developed to
      investigate the vestibulo-ocular reflex (VOR) during everyday activities. The
      test results show that computer simulation of the VOR occurring during complex
      movements is indeed possible. The model was able to predict the trend of the
      experimentally determined eye velocities. It was ascertained that for the further
      development of the model, the influence of the cervico-ocular reflex (COR) on the
      resulting eye velocities also has to be taken into account. The proposed method
      for investigating patients with equilibrium disorders appears suitable enough to
      make further development to the clinical stage worthwhile. An adaptation of the
      feedback amplification parameters of the model to take account of the nature of
      the stimulus and the influence of COR is needed to improve the agreement between
      the amplitudes of measured and predicted eye velocities. To reliably quantify the
      feedback amplification parameters, tests need to be carried out in a large number
      of subjects.

PMID- 8737528
TI  - [Rest-activity cycle in man].
AB  - An actigraph (ZAK company) is a small device that can be worn on the wrist like a
      watch. We carried out a study to compare sleep efficiency and total sleep time as
      determined by actigraphy and polysomnography. The number of body movements per
      minute is a density function. The integrated function shows a virtually constant
      gradient in the wake state and a different constant gradient during sleep. The
      body movement density function per hour provides a useful threshold for correctly
      differentiating between wake and sleep states. This threshold is defined as the
      minimum between the two maxima of the bimodal logarithmic body movement density
      distribution. In the second step we computed a rank scale of the different
      gradients and approximated the integrated function for every scale element using
      linear graphs. The points of intersection of the straight lines define the time
      points for sleep onset and end of sleep. Sleep efficiency is given by SE = 100
      (TST-sleep interruption time)/TST. Total sleep time is the interval between sleep
      onset and end of sleep. Actigraphy is a suitable semi-objective method for
      estimating sleep efficiency and total sleep time, and--for cost reasons--should
      be used for screening before approaching a sleep laboratory. Actigraphy carried
      out over several days shows only small differences in comparison with
      polysomnography. The estimation of parameters is more accurate the longer the
      patient wears the actigraph, and a minimum of five days is recommended. Spectral
      analysis of the intregrated body movement density provides important information
      for detecting subclinical sleep disorders.

PMID- 8737529
TI  - [Scanning electron microscopy studies of morphologic changes in ultra-high
      molecular weight polyethylene materials after various processing steps].
AB  - Scanning electron microscopic (SEM) studies were carried out on various
      orthopaedic implants made of ultra-high molecular weight polyethylene (UHMWPE).
      Both non-sterilized and gamma-sterilized machined (milled) implants were used.
      Milled implants showed significant surface irregularities, and cross-sections
      also revealed irregularities in deeper layers of the polyethylene. In gamma
      sterilized implants, cracks measuring 10-30 microns in length were found at a
      depth of 1.5 to 2.5 mm. Crater-like defects were also occasionally seen. CLINICAL
      RELEVANCE: On the basis of these findings, direct compression moulding and a
      sterilization process in which oxygen is eliminated can be recommended as ways of
      improving the quality of UHMWPE used for orthopaedic implants.

PMID- 8737530
TI  - [Foot stress simulator for biomechanical in vitro studies of lower leg segments].
AB  - In this paper we describe a foot-loading simulator that permits in vitro studies
      on human lower leg and foot specimens. The specimens are fixed in a jig and
      loaded axially with the aid of a pneumatic cylinder. The resulting transfer of
      forces through the ankle joint complex and Chopart's articulation (line) can be
      demonstrated on a pressure-sensitive film. Plantar pressure measurements obtained
      in patients or normal subjects can be used to ensure the comparability of in vivo
      and in vitro measurements. The supporting platform can be tilted in such a manner
      as to provide a range of foot positions up to 20 degrees in plantar- or
      dorsiflexion, eversion or inversion. The system is used for investigating the
      effects on the intra-articular pressures and plantar pressure patterns of
      physiological muscle activity and pathological conditions following fracture of
      the calcaneum or damage to the lateral ligament. By way of an example, the
      effects of muscle forces on plantar pressure distribution are presented.

PMID- 8737531
TI  - [Evaluating error values of pressure measuring systems and their clinical
      relevance].

PMID- 8737532
TI  - [Technical principles of blood pressure monitoring and possible sources of
      error].

PMID- 8737533
TI  - [Pulmonary artery catheter. Theory and practice].

PMID- 8737534
TI  - [Monitoring mechanical function of the heart with reference to pressure-volume
      relations].

PMID- 8737535
TI  - [VO2 and DO2 during cardiogenic shock and infection].

PMID- 8737536
TI  - [Double indicator methods for monitoring in the intensive care unit].

PMID- 8737537
TI  - [Continuous monitoring of minute cardiac volume].

PMID- 8737538
TI  - [Transesophageal echocardiography as intraoperative monitoring of risk patients].

PMID- 8737539
TI  - [Methods of microcirculatory monitoring (laser Doppler flowmetry,
      photoplethysmography and computer-assisted venous occlusion plethysmography)].

PMID- 8737540
TI  - [Terminus technicus "screening and pre-test probability"].

PMID- 8737541
TI  - [Microalbuminuria in diabetes mellitus--illness or symptom?].
AB  - Microalbuminuria (MA) is a term used for urinary albumin excretion between 20 and
      200 micrograms/min. or 30-300 mg/24 h. This definition is not used by all
      authors. In addition, various methods may influence the results. The significance
      of MA concerns the prognosis in diabetics. For the juvenile type 1 diabetes
      nephropathy is the most important complication. In adult type 2 diabetics the
      prognosis concerns mainly cardiovascular death. The excess mortality to be
      attributed to MA is several fold in type 1 diabetes, less in the adult onset type
      variety. MA is the expression of an incipient general disease of blood vessels
      touching as much the kidney as the heart. According to the presence or absence of
      other vascular damage. MA develops toward nephropathy or cardiovascular
      complications. The features leading to or worsening MA are elevated blood
      pressure, poor glucose control, elevated lipoproteins, diminished insulin
      sensitivity and probably smoking. Retinopathy is an indicator for particularly
      sensitive patients responding with the development of MA upon only mildly
      elevated blood pressure or poor metabolic control. The prevalence of MA is close
      to 20% for both types of diabetes. Non-diabetic persons under 60 years of age
      exhibit MA in 2-10%, the elderly in 20-30%. For non-diabetic persons with
      hypertension MA is reported to be present in 19%. Over a time span of 5 years,
      19% of type 1 patients with MA develop proteinuria of more than 300 mg/24 hours.
      In a third of cases albumin excretion normalises. In the remaining half a small
      progression of MA occurs. For type 2 patients the increased mortality risk is
      restricted to the first 5 years, thereafter the survival curves return to those
      of patients without MA. In these patients the excess mortality is already present
      at albumin excretion rates above 10 micrograms/min. Higher values have,
      therefore, to be considered pathological. For the treatment of the syndrome ACE
      inhibitors and ev. Ca-antagonists (with the exception of dihydropyridine,
      nifedipine) are recommended. They reduce albumin excretion by 50%. In a single
      study (yet) with type 1 diabetes mortality also was reduced by 40-50%. This would
      imply that the excess mortality could be halved in patients undergoing this
      treatment.

PMID- 8737542
TI  - [Transplantation and organ donation in Germany].
AB  - Since the first kidney transplantation in Germany 1963 organ transplantation
      progressed in quality and quantity. Despite a very successful development the
      national transplant program stagnates since 1990 with even regression in renal
      transplantation. As number of patients in need of renal replacement therapy has
      grown now to about 40,000 it is of great importance to improve the situation
      especially in regard to kidney transplantation.

PMID- 8737543
TI  - [Rehabilitation of children and adolescents after organ transplantation].
AB  - Today transplantation of different vital organs is an often and successfully
      applied clinical method. After organ transplantation the degree of recovery
      mainly depends on graft function. Besides social, work and school reintegration
      as well as the development of independence and self-responsibility are decisive
      for a general recovery. Therefore a rehabilitation should be planned in the scope
      of the medical care after transplantation. For this reason the rehabilitation
      center for children and juvenile was founded in Stronach, Austria in 1992. Since
      then until March 1995 136 kidney- and 54 liver transplanted patients have been
      treated. There is a significant increase of hemoglobine in all cases and a
      significant decrease of creatinine as a parameter of graft function in kidney
      transplanted patients. By spiroergometric testing the heartrate at the aerobic
      anaerobic threshold can be easily estimated in children and juvenile and in
      consideration of these results the physical endurance can be distinctively
      increased by an individual training program.

PMID- 8737544
TI  - [25 years kidney replacement therapy in childhood and adolescence--success of
      somatic and psychosocial rehabilitation].
AB  - In the late sixties, renal replacement therapy (RRT) was started in terminal
      renal insufficient children and adolescents. The high mortality rate and extreme
      therapeutic difficulties gave doubts to the possibility of longterm survival as
      well as somatic and psychosocial rehabilitation in these patients. But nowadays
      due to improvements in medical and technical possibilities of dialysis and kidney
      transplantation as well as to individually adapted treatment of the metabolic
      problems 5-years survival rate is more than 90%, body growth and development is
      in the lower normal range. Successful psychosocial rehabilitation despite RRT has
      also improved over time. In the beginning only 29% dialysed patients and 51%
      transplanted children attended school and 65% completed school. A recent analysis
      of educational status employment rate and social situation in 617 patients
      between 20 and 35 year of age who started RRT as children in Europe and 276
      terminal renal insufficient adolescents in Germany, gave following results: one
      third went to vocational training, 11-17% attended university. Thereafter 40-65%
      of all patients were employed. Unemployment was a big problem in dialysed
      adolescents and young adults. With increasing age the patients gained
      independence in their life style. About 20% lived in their own houses, 28% were
      either married, divorced or widowed, 8% had children of their own.

PMID- 8737545
TI  - [Geriatrics, a social medicine challenge].
AB  - The number of old people in our society is strongly increasing. In 1960 1.4
      percent of the German population were older than 80 years, in 1993 this
      percentage was 3.8. 4000 persons older than 100 years are living in Germany
      today. A great number of these old people are ill and in need of help, often
      being multimorbid. It has to be the task of geriatrics to increase the number of
      symptom-free years and to relieve arising diseases.--Cardiovascular and cancer
      diseases--the leading diseases in our society--are for the most part caused and
      maintained by external factors. But genetic defects are also increasingly getting
      involved. About 5000 genetic defects in man have been described so far and
      results of the latest research suggest that every human being has four to eight
      pathologically changed genes. Which effects these genes have in the course of
      life is still the question. Environmental influences play an important role, also
      in genetically caused diseases.--The care insurance, recently established in
      Germany, involves considerable dangers. Most of the sick people who are in need
      of care are being nursed in families and households. These possibilities should
      be made use of also in the future. The number of people demanding care benefits
      will continuously rise in the coming years and the extent of necessary financial
      support is threatening to increase excessively. Bureaucratic selection procedures
      should be avoided. An important role will come up to the doctors in this field.
      It must be avoided letting the cultural evolution get out of control. This is
      also true for the field of geriatrics and gerontology.

PMID- 8737546
TI  - [The elderly as accident victims--an overview].
AB  - Accidental death is the most important non-natural death in the age-group. Old
      age people with physiological and pathological alterations especially will be
      endanger by traffic accidents and downfall-injuries.

PMID- 8737547
TI  - [External fixation of bones (fixateur externe) in fracture treatment].
AB  - In traumatology, we differentiate between conservative and surgical treatment.
      External fixation of the bone lies somewhere between the two. When deciding on
      the most appropriate treatment for each patient, the advantages and disadvantages
      must be carefully evaluated. However, there are a series of single or multiple
      injuries which can't be optimally treated with conservative procedures nor with
      invasive surgery. External fixation has become the treatment method of choice in
      many of these cases. The fragments to be stabilised are fixed with (so-called
      Schanz screws) or with (Steinmann pins) or with wires. The section which lies
      outside the body are attached to longitudinal rods. External fixation is a
      noninvasive, surgical method of fracture stabilisation with many advantages is
      easy to handle, has a low complication rate, can be taught anywhere, and can be
      used everywhere. There are great advantages in cases of soft tissue damage, in
      polytraumatised patients and in septic orthopedic surgery.

PMID- 8737548
TI  - [Survey of alcohol drinking and results of studies of alcoholism biological
      markers within the scope of a neurologic occupational medicine study of
      industrial workers].
AB  - As part of a combined neurological and occupational-medical study about
      potentially neurotoxic agents consumption of alcohol of the probationers as
      possible influential factor on the nervous system was evaluated. Therefore an
      injury of industrial workers of different nationalities was performed about the
      individual alcohol consumption combined with an investigation about so-called
      alcoholism-markers [gamma-Glutamyltranferase (gGT), mean corpuscular erythrocytes
      volume (MCV) and Carbohydrate-deficient Transferrin (CDT)]. It was the aim of the
      study, to give an overview of the amount of alcohol consumption in male
      industrial workers - and to examine, to what extent connections exist between
      alcoholism markers and the amount of individual alcohol consumption. We found a
      high percentage of probationers with alcohol abstinence (53%). The test persons
      with anamnestic alcohol consumption indicated a mean alcohol consumption of 33,7
      g per day (6 to 240 g/d). A significant correlation between changes of laboratory
      markers and amount of alcohol consumption could only be found for CDT. In
      addition there was a correlation of CDT with gGT and MCV and of gGT with MCV, but
      with very small correlation coefficients. After multiple logistic regression and
      establishing of a prediction model of the consumption of alcohol under knowledge
      of laboratory results an assignment of the probationers to the respective group
      (abstinents and/or consumers of alcohol) was not successful with sufficient
      safety. According to our data in a normal collective a determination of
      laboratory parameters, which are discussed as alcoholism markers, does not
      contribute to better delimitation of abstinent living and alcohol drinking
      persons and to a better knowledge of the amount of alcohol consumption.

PMID- 8737549
TI  - [Doping--anabolic steroid abuse--careless homicide].
AB  - Proceeding from a case requiring an expert's opinion (competitive athlete from
      the GDR), the question of damage to the health after the abuse of anabolic
      preparations is being discussed once again. In this connection, however, it is
      not only necessary to look at the cases that have come to light in the
      competitive sports sector (doping) but also at cases involving the body-building
      movement. Damages to the liver, in particular liver tumors, are described, among
      others. But vascular diseases are also described. Auto-aggression and aggression
      toward others can, however, also entail a forensic/psychiatric report, and,
      finally, the forensic-medicine expert can be challenged when manipulations of the
      urine specimens to be examined are involved (DNA analyses). From the legal point
      of view, doping cases will constantly pose the question of whether the athletes
      concerned knew what they were being "treated" with. Quite apart from forensic
      questions, however, it will also be necessary to discuss the overall complex from
      the point of view of medical ethics. Every time a case becomes known, damage is
      done once again to the idea that sports are supposed to bring nations together
      and promote peace.

PMID- 8737550
TI  - Dyslipidemia in chronic renal failure patients.

PMID- 8737551
TI  - Is there an endemic focus of kala azar in Bombay?

PMID- 8737552
TI  - Dyslipidemia in patients with chronic renal failure and in renal transplant
      patients.
AB  - Indian studies on lipid profile abnormalities in chronic renal failure (CRF) have
      varied from no abnormalities at all to significant abnormality
      (hypertriglyceridemia and reduced HDL) as described in the Western literature.
      Moreover, there is no Indian study on the effect of renal transplantation on the
      abnormal lipid profile of CRF. The aim of our study was to determine the lipid
      profile of CRF patients on conservative treatment, end stage renal disease (ESRD)
      patients on maintenance hemodialysis (HD) treatment and renal transplant
      patients. We also looked at the effect of fish oil rich in polyunsaturated fatty
      acids (Max-EPA) on hypertriglyceridemia of CRF. The study included 4 groups; Gp
      I: control subjects (n = 9, age = 30 +/- 5 yrs), Gp II: CRF patients on
      conservative treatment (n = 9, age = 49 +/- 17 yrs), Gp III: ESRD patients on HD
      for at least 3 months (n = 19, age = 53 +/- 9 yrs), Gp IV: 3 months post-renal
      transplant patients (n = 9, age 31 +/- 11 yrs). The lipids and lipoproteins
      analysed include total cholesterol, HDL, LDL, triglycerides, Apo A1 and Apo B. It
      was observed that in Gp II patients triglycerides were significantly elevated (p
      < .05) and Apo A1/Apo B significantly abnormally lower (p < .001) compared to Gp
      I. In Gp IV patients, there was no significant difference in lipid profile
      compared to Gp I. With the use of Max-EPA in 5 patients with
      hypertriglyceridemia, there was a significant improvement in hypertriglyceridemia
      (p < .05). Our study suggests: 1) significant hypertriglyceridemia does develop
      in a majority of CRF patients. The abnormality probably improves with dialysis
      treatment and renal transplantation. 2) A lower Apo A1/Apo B ratio in CRF
      patients may account for higher risk of atherosclerosis. 3) Fish oil rich in
      polyunsaturated fatty acids improves hypertriglyceridemia of CRF.

PMID- 8737553
TI  - Post-operative pain relief in children following caudal bupivacaine and
      buprenorphine--a comparative study.
AB  - Eighty-five paediatric patients (age range: 6 mths-12yrs) undergoing lower
      abdominal surgery were studied for post-operative pain relief following either
      caudal bupivacaine (GpI: n = 43) or buprenorphine (GpII: n = 42). Bupivacaine was
      administered as 0.5ml/kg body weight of 0.25% solution and buprenorphine as 4
      micrograms/ml and volume of 0.5 ml/Kg body weight in normal saline. Post
      operatively pain was graded on a 4-point scale and behaviour on a 5-point scale.
      Any post-operative complications and need for additional analgesia were also
      noted. Bupivacaine provided good pain relief in the early post-operative hours
      but buprenorphine provided pain relief lasting for 24 hrs or more post
      operatively. Post-operative behaviour of 10 patients receiving buprenorphine was
      graded as cheerful as compared to 2 from bupivacaine group. Till the end of
      observation period (i.e. 8 hr post-operatively), majority of patients receiving
      buprenorphine remained cheerful.

PMID- 8737554
TI  - Modulation of Kupffer cell activity by Tinospora cordifolia in liver damage.
AB  - Kupffer cells are major determinants of outcome of liver injury. Their activity
      was therefore studied in a model of chronic liver disease. The effect of
      Tinospora cordifolia, an indigenous agent with proven hepatoprotective activity,
      was evaluated on Kupffer cell function, using carbon clearance test as a
      parameter. Rats were divided into two major groups. In Gp I which served as
      normal control t1/2 of carbon was 9.48 +/- 4.14 min. GpII received horse-serum in
      a dose of 0.5 ml/100 gm b.w. i.p. for a period of 12 weeks and was divided into
      three sub-groups. In Gp IIA at the end of 12 weeks half-life of carbon was found
      to be significantly increased to 19.86 +/- 7.95 min (p < 0.01). Indicating
      suppressed Kupffer cell function in chronic liver damage. In Gp IIB treated with
      vehicle for 4 more weeks there was significant prolongation of half-life to 38.32
      +/- 10.61 min (p < 0.01), indicating perpetuation of damage in absence of
      damaging agent. Whereas in Gp IIc, treated with Tinospora cordifolia t 1/2 was
      decreased to 14.24 7.74 min (p < .01), as compared to vehicle control indicating
      a significant improvement in Kupffer cell function and a trend towards
      normalization.

PMID- 8737555
TI  - A 18 years study of testicular tumours in Jodhpur, western Rajasthan.
AB  - The present study based on WHO histologic typing of testicular tumours deals with
      100 cases recorded in the files of the Department of Pathology from 1969 to 1987.
      These tumours accounted for 2.57% malignancies of male genital system. Maximum
      number of tumours were recorded in the third and fourth decades. Right testis was
      affected in 60% cases. Scrotal swelling was the predominant presenting feature,
      followed by pain. Five cases of testicular tumours were observed in undescended
      testis. Germ cell tumour of one histologic type constituted 76% of testicular
      tumors. Germ cell tumors of more than one histologic type were 23%. One case (1%)
      belonged to lymphoid and haemopoietic system and was of large cell lymphocytic
      lymphoma. Amongst the germ cell tumors with one histologic type, seminoma (34%)
      and embryonal carcinoma (28%) were predominant while teratocarcinoma was a
      predominant tumour in combination group.

PMID- 8737556
TI  - Synchronously performed prostatic fine needle aspiration and core biopsies--an
      appraisal.
AB  - One hundred and twenty-six patients underwent fine needle aspiration (FNA) and/or
      core biopsies of the prostate in a rurally located, non-oncospecialised
      organisational setting. The procedures were performed by the residents of varying
      seniority and experience. While a simple core biopsy alone had a greater
      diagnostic potential, (37/45) FNA was found to be a rapidly interpretable
      sampling methodology with consequent reduction of waiting period for diagnosis
      and institution of treatment. The two techniques taken together complemented each
      other by avoiding repeat biopsies, delaying diagnosis and therapy. In case FNA
      turned out to be inconclusive, the report on core biopsy would follow soon,
      unlike in a situation where they are done asynchronously.

PMID- 8737557
TI  - The role of early trabeculectomy in the control of chronic simple glaucoma.
AB  - Seventy patients of bilateral chronic simple glaucoma with a mean age of 59.7
      years, an intra-ocular pressure over 25 mmg Hg, optic disc cupping, and without
      visual field loss were selected. The eye with higher intra-ocular pressure or the
      larger optic disc cup was treated by early trabeculectomy while the other eye of
      the same patient was subjected to medical therapy with topical beta blockers for
      3 years (without any surgical treatment). Both the eyes of 70 patients were
      compared after 3 years. Eyes which had undergone trabeculectomy had a mean intra
      ocular pressure of 11.7 mm Hg against 18 mm Hg in the medically treated eyes.
      Surgically treated eyes had decrease in the mean cup : disc ratio (from 0.54 : 1
      to 0.48 : 1) whereas medically treated eyes showed an increase from 0.41:1 to
      0.51: 1. Visual field loss occurred in 3/70 operated eyes and in 27/70 medically
      treated eyes. Twenty-one of 70 treated eyes developed cataract and 12 of these
      required cataract surgery. Only 18/70 medically treated eyes developed cataracts
      but none of these required cataract surgery. Early trabeculectomy in cases of
      chronic simple glaucoma resulted in a large reduction of intra-ocular pressure
      and consequently reduced the size of optic disc cup and the chances of visual
      field loss.

PMID- 8737558
TI  - End-tidal carbon dioxide detectors--are they useful in children?

PMID- 8737559
TI  - Acquired tracheo-oesophageal fistula.
AB  - Acquired tracheo-oesophageal fistula is rare. The most common causes are
      tuberculosis and malignancy. Here we report a patient who had come with dysphagia
      and aspiration pneumonia with paratracheal lymphnodes on X-ray chest and was
      diagnosed to have a tracheo-bronchial fistula on barium studies. Transtumoral
      intubation by pull-through method was carried out.

PMID- 8737560
TI  - Localization of a pheochromocytoma using I-123 MIBG adrenal scintigraphy.
AB  - In a patient with the clinical diagnosis of pheochromocytoma, the localization of
      the tumor is essential for planning treatment. Recently, we have performed I-123
      metaiodobenzylguanidine (MIBG) adrenal scintigraphy in a patient presenting with
      a history of paroxysmal hypertension. Scintigraphy accurately located an ectopic
      unilateral pheochromocytoma. The scintigraphic diagnosis was confirmed by surgery
      and a diagnosis of ectopic unilateral pheochromocytoma was made by
      histopathological examination. This case report illustrates the specific
      diagnosis of pheochromocytoma by I-123 MIBG scintigraphy which is especially
      useful when other diagnostic procedures are equivocal.

PMID- 8737561
TI  - Penicillium species causing onychomycosis.
AB  - Onychomycosis caused by mould infection is rare. A 40 year old male patient
      presented with dystrophic finger nails and multiple, erythematous lesions with
      slightly raised borders and scaling all over the body. The patient was a known
      diabetic. He did not respond to griseofulvin. Samples from nails and skin scales
      were cultured. From the nails, Penicillium species and from the skin scales.
      Trichophyton rubrum were isolated. Ketoconazole therapy (200 mg twice daily x 4
      mths) led to complete cure with negative cultures and normalization of nails.

PMID- 8737562
TI  - Dual isolation technique for paediatric lung surgery.
AB  - This report describes a dual isolation technique adopted to isolate the lungs
      from one another at the time of right pneumonectomy in a child (age: 5 yrs, 10 kg
      weight) with evidence of infective lung disease associated with copious purulent
      secretion and compromised respiratory function. The isolation of right lung from
      left was achieved by placing Fogarty embolectomy catheter in right main bronchus
      and a plain polyvinylchloride endotracheal tube (which was aseptically preshaped
      to have a distal 45 degrees angulation towards left) in left main bronchus. No
      soiling of left lung occurred during surgery and patient remained hemodynamically
      stable. In the same child, post-thoracotomy pain was relieved for five days with
      buprenorphine, administered through a lumbar epidural catheter. The child had an
      uneventful post-operative course and cooperated for physiotherapy.

PMID- 8737563
TI  - Multiple myeloma presenting as proliferative (crescentic) glomerulonephritis.
AB  - Glomerular extracapillary cellular proliferation with crescent formation
      initially presenting as rapidly progressive glomerulonephritis is a rare clinical
      manifestation of multiple myeloma. We report here a case of a 58 year old female
      who initially presented with haematuria, loss of weight and appetite and history
      of febrile episodes and was diagnosed following renal biopsy as rapidly
      progressive glomerulonephritis. Haemodialysis was carried out a month later
      because of uremic symptoms and maintained with monitoring of serum, calcium,
      phosphate, alkaline phosphatase, albumin and iPTH levels. After 6 months, she
      complained of bone pains over anterior chest wall which persisted even with low
      calcium haemodialysis. Serum protein electrophoresis and bone marrow aspiration
      revealed multiple myeloma. On starting chemotherapy, bone pain subsided but the
      patient expired within 15 days of therapy.

PMID- 8737564
TI  - Adenoid cystic carcinoma of the cervix in a young patient.
AB  - Adenoid cystic carcinoma of the cervix is a rare disease. It usually occurs in an
      elderly age group. A case who presented at a younger age (30 years) is being
      reported. The chief complaint was excessive vaginal bleeding for 2 months. Per
      vaginum examination revealed a growth. She was staged FIGO IIIb. She was treated
      with radical radiotherapy. Disease regressed slowly and complete local response
      appeared after six months of treatment. Presentation of adenoid cystic carcinoma
      in younger age group and effect of radiotherapy in advanced stage is reviewed.

PMID- 8737565
TI  - Statistics in medical research--V. Some non-parametric tests.

PMID- 8737566
TI  - Pericardial systolic sound mimicking peristalsis--a clue to hiatus hernia.

PMID- 8737567
TI  - [Formation of so-called byproducts (propanols, butanols et al.) from ethanol by
      microorganisms].
AB  - Microbiological literature implies and furnishes evidence that aliphatic alcohols
      and the corresponding carboxylates as well as acetone can be produced from
      ethanol during microbial metabolic processes. Propionate/propanol-1 followed by
      butyrate can be obtained by means of step-by-step reductive carboxylation of
      acetyl-CoA. Both butyrate/butanol-1 and caproate/hexanol-1 are typical
      fermentation products of Clostridium kluyvery. In cases where butyrate
      decomposition is disrupted up to 50% of butyrate is isomerised to isobutyrate. In
      addition to ethanol, butyrate and butanol-1, isopropanol and acetone are
      characteristic products of commercially used Clostridia. One would expect that
      saccharolytic organisms producing ethanol in addition to other "solvents"
      (butanol-1, acetone, isopropanol) can also synthesise the solvents if the
      substrate is changed (ethanol instead of carbohydrate). Under carbon monoxide,
      formiate and hydrogen, some CODH-active Clostridia can, very efficiently, convert
      various carboxylates into the corresponding alcohols. There are several groups of
      organisms present in human intestinal tract that can utilise ethanol and other
      alcohols.

PMID- 8737568
TI  - [Lowering the promille limit?].
AB  - The Legislator's decision not to lower the 0.8 per mile alcohol level limit of
      the section 240 StVG runs counter to the tendency of fighting dring driving
      altogether. This decision was made despite the fact, that according to current
      medical science the risk limit lies at 0.4 per mile. It can't be justified by the
      "ultima ratio" principle which was introduced by the legislator for decision
      making. Much on the contrary, it suggests a development where considerations will
      no longer be applied only for the protection of the citizen. Here we can observe
      a continuation of the interpretation of the alcohol level limits which seem to
      simply serve as a means of ensuring a conviction. The economical analysis of the
      law is the theoretical background to this consideration which dominated by this
      process. This analysis does not take any further limitations of legislative
      powers into consideration with the exception of effectiveness, efficiency and its
      maximum use under the political and economic aspects. Therefore it allows the
      protection of the individual to be obscured by these maxims. However, lowering of
      the alcohol level risk limit to 0.4 per mile should not be insisted on, but
      instead there should be a call for the introduction of an alcohol ban altogether.
      This request could be justified with the lack of the legal basis of the alcohol
      level limits.

PMID- 8737569
TI  - Large-scale perfusion culture process for suspended mammalian cells that uses a
      centrifuge with multiple settling zones.
AB  - A high-cell-density perfusion culture process, using a novel centrifuge, was
      developed. The centrifuge has spiral multiple settling zones to separate cells
      from culture medium. Because of the multiple zones, the separation area can be
      efficiently increased without enlarging the diameter of the centrifuge. The
      centrifuge used in this study had a separation capacity of 2600 ml culture medium
      min -1 at 100 g of the centrifugal force. A new cell separation and withdrawal
      method was also developed. The cells separated in the centrifuge can be withdrawn
      easily from the centrifuge with no cell clogging by feeding a liquid carrier such
      as a perfluorocarbon into the centrifuge and pushing the cells out with the
      liquid carrier. By this culture process, monoclonal antibodies were produced with
      mouse-human hybridoma X87X at a cell density of about 8 x 10(6) cells ml -1 for
      25 days. This centrifuge culture shows promise as a large-scale perfusion culture
      process. (Himmelfarb et al. 1969; Feder and Tolbert 1983) usually have the
      problem of filter clogging, and perfusion culture processes with gravitational
      cell settling (Tokashiki and Arai 1989) are limited in scale-up because of low
      separation efficiency. Recently centrifugal separation of cells from culture
      medium has been used for perfusion culture processes (Hamamoto et al. 1989;
      Tokashiki et al. 1990; Apelman 1992; Jager 1992). This process essentially has a
      high separation efficiency and can avoid further operational problems, such as
      filter clogging, by the type of filtration. To investigate the scale-up
      feasibility of the centrifuge culture system, we have developed a new type of
      centrifuge with four layers of spiral cell-settling zones to increase the
      separation area, and a novel cell separation and withdrawal method using a
      perfluorocarbon.

PMID- 8737570
TI  - Studies on the inactivation of the flavoprotein D-amino acid oxidase from
      Trigonopsis variabilis.
AB  - Inactivation of D-amino acid oxidase occurred by different mechanisms. The enzyme
      showed a rapid loss of activity in the presence of micromolar amounts of Cu2+ and
      Hg2+. It was also sensitive to oxidative inactivation by Fe2+ and H2O2 when both
      reagents were added in millimolar amounts. When oxidatively inactivated D-amino
      acid oxidase and a corresponding non-treated control were modified with the
      sulfhydryl-modifying, fluorescent reagent monobromobimane and subsequently
      digested with endoproteinase Glu-C, Cys-298 was identified to be a target for
      oxidative modification according to differences in the known peptide profile of
      fluorescence intensity. Another reason for the observed loss of enzyme activity
      in crude extracts was the specific proteolytic digestion of D-amino acid oxidase,
      which was dependent on the growth phase of the cells used. This cleavage was
      catalyzed by a serine-type proteinase and was the introductory step for the
      further complete degradation of the enzyme. In addition, a coenriched 50-kDa
      protein, identified as NADPH-specific glutamate dehydrogenase, significantly
      decreased the stability of the D-amino acid oxidase activity. Treatment of apo-D
      amino acid oxidase from T. variabilis with monobromobimane resulted in a
      significantly increased fluorescence of two peptides, neither of which contained
      any cysteine residue. Thus, an involvement of cysteine residues in binding the
      FAD coenzyme should be excluded.

PMID- 8737571
TI  - Optimization of environmental factors for the production and handling of
      recombinant retrovirus.
AB  - Certain steps from the production to infection of the amphotropic retroviral
      vector, MFG- LacZ, were optimized and the factors that affect retroviral titers
      were analyzed. Retroviral vector titers were highest when the culture supernatant
      was harvested 3 days after the producer cells had reached confluence. About a 2
      fold increase in vector production was achieved at 32 degrees C compared to that
      at 37 degrees C. Low serum concentrations had no significant effect on the titers
      of virus produced by the CRIP cell line. Retroviral vectors were stable at 4
      degrees C but very unstable at 37 degrees C and were quite sensitive to freezing
      and thawing. About 30%-50% of viral infectivity was lost during the thawing step
      and the loss was not recovered by the addition of commonly used cryoprotectants.
      Increase in viral exposure time for infection to target NIH3T3 cells was linearly
      proportional to the retroviral titer for up to 15 h. In addition, using DEAE
      dextran in place of polybrene as a polycation during infection enhanced infection
      efficiency about 3-fold. The retrovirus was robust to simple ultrafiltration and
      its titer could be easily concentrated 16-fold. Taken together, our data suggest
      that at least a 100-fold increase in titer can be achieved with simple
      optimization.

PMID- 8737572
TI  - Construction of an integrative food-grade cloning vector for Lactobacillus
      acidophilus.
AB  - An integrative cloning vector was constructed using a randomly cloned HindIII
      digested chromosomal fragment from Lactobacillus acidophilus ADH inserted into an
      Escherichia coli vector, pBluescript II SK+. Southern hybridization studies
      demonstrated homology of the inserted fragment with one other L. acidophilus
      strain and one Bifidobacterium strain. Identification of a SauI site located near
      the middle of the 1.9-kb ADH chromosomal fragment made it possible to clone the
      Lactobacillus bulgaricus beta-galactosidase (EC 3.2.1.23) gene into this vector.
      The vector was unable to replicate in the homologous host, L. acidophilus ADH,
      following electroporation. The chromosomal fragment allowed the integration of
      the beta-galactosidase gene (beta gal) into the host chromosome via homologous
      recombination. The size of the two flanking L. acidophilus ADH chromosomal
      fragments, approximately 0.95 kb each, was sufficient to allow the double cross
      over to take place. Southern hybridization demonstrated that only L. acidophilus
      and L. bulgaricus DNA had been integrated into the chromosome of the host strain.
      The beta-galactosidase activity of the transformant was increased approximately
      200-fold when compared to the enzyme activity of the wild-type strain. The beta
      gal gene remained stable in the transformant strain after 30 transfers in growth
      media without selection pressure. This first-generation integrative cloning
      vector is constructed solely of DNA from organisms consumed by humans and could
      be considered a food-grade vector system.

PMID- 8737573
TI  - Organization and expression in Pseudomonas putida of the gene cluster involved in
      cephalosporin biosynthesis from Lysobacter lactamgenus YK90.
AB  - The Lysobacter lactamgenus YK90 pcbAB gene encoding delta-(L-alpha-aminoadipyl)-L
      cysteinyl-D-valine (ACV) synthetase is located immediately upstream of the pcbC
      gene in the same orientation in the gene cluster involved in cephalosporin
      biosynthesis. The pcbAB gene encodes a large polypeptide composed of 3722 amino
      acid residues with a molecular mass of 411593 Da. The predicted amino acid
      sequence has a high degree of similarity with those of known ACV synthetases from
      fungi and actinomycetes. Within the pcbAB amino acid sequence, three conserved
      and repeated domains of about 600 amino acids were identified. the domains also
      share a high degree of similarity with non-ribosomal peptide synthetases such as
      gramicidin synthetase 2 of Bacillus brevis. The pcbAB gene was expressed under
      the control of the lac promoter in Pseudomonas putida. Expression of the gene
      cluster involved in cephalosporin biosynthesis in P. putida led to the
      accumulation of beta-lactam antibiotics. Deletion analysis of an open-reading
      frame located between the cefE and cefD genes from the gene cluster revealed that
      it encoded deacetylcephalosporin C synthetase (cefF). From the results presented
      here and those of previous studies, the genes involved in cephalosporin
      biosynthesis in L. lactamgenus appear to be clustered in the order pcbAB-pcbC-
      cefE-cefF-cefD-bla in the same orientation within a 17-kb region of DNA.

PMID- 8737574
TI  - Characterization of two bioluminescent Rhizobium meliloti strains constructed for
      field releases.
AB  - The deliberate release of genetically engineered microorganisms requires a
      thorough characterization of the microbes in question. For the two bioluminescent
      Rhizobium meliloti strains, L1 and L33 [Selbitschka et al. (1992) Mol Ecol 1:9
      19; Selbitschka et al. (1995) FEMS Microbiol Ecol 16:223-232], designated for
      field release, the sites of genetic modifications in the chromosomes were
      sequenced from amplified genomic DNA. This indicated no unexpected alterations in
      the nucleotide sequence. The bioluminescent phenotype was stably inherited over
      more than 100 generations in liquid cultures. The presence of the luciferase gene
      in both strains did not have secondary effects on a variety of metabolic pathways
      as assessed by the Biolog GN system. A specific polymerase chain reaction
      amplification, based on the chromosomal insertion site of the luc cassette,
      allowed the discrimination between the two strains and thus simplifies
      monitoring. The RecA-deficient strain L1 showed a strongly (more than 90%)
      reduced ability to nodulate alfalfa in competition with its parent strain R.
      meliloti 2011 and its RecA+ counterpart L33.

PMID- 8737575
TI  - Arabinoxylan-degrading enzyme system of the fungus Aspergillus awamori:
      purification and properties of an alpha-L-arabinofuranosidase.
AB  - An alpha-L-arabinofuranosidase produced by the fungus Aspergillus awamori had a
      molecular mass of approximately 64 kDa on sodium dodecyl sulphate/polyacrylamide
      gel electrophoresis (SDS-PAGE) and was optimally active at pH 4.6 and 50 degrees
      C. The enzyme, which chromatographed as a single component on SDS-PAGE, appeared
      to consist of two isoenzymes of pI 3.6 and 3.2. Acting in isolation, the alpha-L
      arabinofuranosidase had only a very limited capacity to release L-arabinose (less
      than 11%) directly from arabinoxylans that had been extracted from a number of
      plant cell wall preparations using 18% alkali, but a much higher proportion of
      the L-arabinose (46%) was released from a wheat straw arabinoxylan that had been
      isolated by steam treatment. There was a marked synergistic effect between the
      alpha-L-arabinofuranosidase and an endo-(1 --> 4)-beta-D-xylanase produced by A.
      awamori in both the rate and extent of the release of L-arabinose from both oat
      straw and wheat straw arabinoxylans, suggesting that L-arabinose-substituted
      oligosaccharides generated by the endoxylanase action were better substrates for
      enzyme action. A novel property of the alpha-L-arabinofuranosidase was its
      capacity to release a substantial proportion (42%) of feruloyl L-arabinose from
      intact wheat straw arabinoxylan. The concerted action of the alpha-L
      arabinofuranosidase and endoxylanase released 71% of the feruloyl L-arabinose and
      69% of the p-coumaroyl L-arabinose substituents from wheat straw arabinoxylan.

PMID- 8737576
TI  - The single-batch bioconversion of wheat straw to ethanol employing the fungus
      Trichoderma viride and the yeast Pachysolen tannophylus.
AB  - We have developed and optimized a single-batch process of the production of
      ethanol from wheat straw employing the fungus Trichoderma viride and the yeast
      Pachysolen tannophylus. T. viride and Aspergillus niger were examined for their
      ability to produce fermentable sugars from cellulosic waste materials, e.g.
      different kinds of straw and wood waste. T. viride most efficiently saccharified
      delignified wheat straw within 3 days at 25-30 degrees C with a yield of reducing
      sugars of 27 g from 50 g delignified wheat straw. The resulting wheat straw
      hydrolysates contained xylose and glucose in a 1:1.6 molar ratio. After heat
      inactivation of fungal activities the sugars were converted to ethanol by the
      oxygen-tolerant yeast P. tannophylus in the same batch. Under the optimized
      conditions developed (all weights are per liter) 70 g natural untreated wheat
      straw (100%) yielded 50 g delignified straw (71.4%), which was saccharified to 27
      g reducing sugars (38.6%). Fermentation of the sugars yielded 11.8 g ethanol
      (16.9%) and followed the molar equation: 1 xylose + 1.6 glucose --> 5.3 ethanol +
      5.6 CO2.

PMID- 8737577
TI  - [Routine antibiotic administration--consider risks and benefits!].

PMID- 8737578
TI  - [Prophylactic and therapeutic use of antibiotics in trauma surgery].
AB  - Antibiotic treatment in traumatology (either for prophylactic or therapeutic
      purposes) can reduce the local bacterial contamination and can therefore improve
      the balance in favor of the host defence capacity. Above all, its value has to be
      measured depending on the local bacterial colonization in the individual case and
      to what extent this is the essential pathogenetic factor for development of the
      infection or for resistance to infection. In situations where local host damage
      (either traumatic or iatrogenically/surgically induced) is the predominant
      cofactor for the development or persistence of infection, the antibiotic or other
      pharmacological reduction of the bacterial colonization is of secondary or no
      importance at all. In view of this, the indications for routine antibiotic
      prophylaxis or therapy, which so far have been accepted as valid, should be
      reconsidered. On the one hand, excellent hygienic conditions have increasingly
      reduced the relative importance of bacterial contamination in aseptic procedures.
      On the other hand, the surgical-technical evolution in the last 5 years (such as
      biological osteosynthesis, unreamed intramedullary nailing, stepwise definite
      stabilization in complex fractures, initial open wound treatment and very early
      plastic reconstruction in open fractures, as well as radical necrectomy in
      chronic infection of bones and soft tissues) could create a significant
      improvement in the conditions concerning prevention and treatment of infection.
      Therefore, the relative importance of adjuvant antibiotic treatment is
      considerably less. Based on previous studies, the publications of the past 3
      years focusing on this aspect are examined critically. Finally, detailed
      recommendations are defined and advice given for well-aimed, controlled
      continuation studies.

PMID- 8737579
TI  - [Classification of distal radius fractures and its diagnostic value].
AB  - In the conservative treatment of distal radial fractures the main problem is
      redislocation due to instability. We evaluated the three classification methods
      most often used to find out how well the different groups correspond to
      instability and severity of fractures-thus what their prognostic value is in the
      probable recovery time. Based on an analysis of 633 cases, we found that neither
      the most often used Frykman nor the AO and older classifications have any
      practical significance in this respect.

PMID- 8737580
TI  - [Prevot nailing, an elegant method. Experiences with 38 personal cases].
AB  - Endomedullar elastic stabilization with titanium Prevot nails is an excellent
      method of treating long-bone fractures in children. Without touching the
      epiphyseal line, this method guarantees early functional follow-up treatment with
      minimal operative trauma. For this reason, this method can compete successfully
      with common methods like extension treatment, external fixation and
      osteosynthesis with plates. From October 1990 to October 1993 we treated more
      than 40 fractures with Prevot nails and checked 38 of them clinically and
      radiologically. All 17 femur fractures healed correctly from an anatomical point
      of view and without rotation defects. In 4 patients we found a maximum difference
      in length of 1 cm in favor of the operated side. All of the 11 forearm fracture
      had good results, but there were 2 poor results with delayed union (adult
      patients) in the 6 humerus fractures operated upon. The remaining 4 cases, had to
      do with exceptional indications like lower leg fractures, combined humerus and
      forearm diaphyseal fractures, and metacarpal diaphyseal fractures. Our first
      experience with this method is good. The duration of hospitalization is short and
      early functional follow-up treatment for pediatric diaphyseal fractures is in
      general practicable. This procedure for operative care of femur and forearm
      diaphyseal fractures has now become the standard therapy in our clinic.

PMID- 8737581
TI  - [Intraoperative and postoperative insertion control of anterior cruciate ligament
      plasty. A radiologic measuring method (quadrant method)].
AB  - The best proximal insertion for an ACL graft is an anatomic insertion. The
      anatomic landmarks of this insertion area are well known, but it is sometimes
      difficult to find these anatomic landmarks during the operation. Thus, it is
      desirable to have an objective method to control the insertion. This study was
      undertaken because no description is available how you can localize the
      projection of the anatomic ALC insertion exactly in an X-ray picture. We
      dissected ten human cadaveric knees with intact ACLs. The most ventral, dorsal,
      distal and proximal borders of the insertion area were marked with 4 K-wires. The
      K-wires were shortened exactly on the bone border of the intercondylar space.
      Then the knees were X-rayed in a strictly lateral position. Thus, the shortened
      ends of the K-wires determined the projection of the ACL insertion in the X-ray
      picture. The center of this marked area was called point K. Then we determined 4
      distances in the X-ray picture: distance t: the sagittal diameter of the lateral
      condyle, measured along the Blumensaat line distance h: the maximal height of the
      notch distance a: the distance between K and the dorsal border of the condyle,
      measured along t distance b: the distance between t and K, measured on a
      perpendicular line on t Distance a is a partial distance of t and distance b is a
      partial distance of h. Because of varying projection factors and varying knee
      sizes, absolute values of these distances are not helpful. This is the reason why
      we expressed a and b as a proportion of t and h. Distance a was measured 24.8% of
      distance t. Distance b was measured 28.5% of distance h. The maximal deviation of
      a and b was 2.2% and 2.5%. Therefore, you can say: In a strictly lateral X-ray
      picture the distance of K (midpoint of proximal ACL insertion) from the dorsal
      border of the condyle is 24.8% of the whole diameter of the condyle, and the
      distance of K from the roof of the notch is 28.5% of the notch-height. This
      method does not depend on the size of the knee and the distance between the X-ray
      unit and the knee. The only condition is that the X-ray of the knee must be
      strictly lateral. This method is easy to handle and is reproducible. It can be
      used intraoperatively if the surgeon is not sure about the right insertion or if
      the anatomic landmarks cannot be seen exactly. It can be used postoperatively for
      documentation of the right position of the substitute. It can be used to find out
      the possible reason for rupture of a transplant (insertion too ventral) before
      the revision operation.

PMID- 8737582
TI  - [Surgical treatment of acute, complete acromioclavicular joint dislocation.
      Indications, technique and results].
AB  - From June 1983 to May 1990, 51 patients were operated on for acute, complete
      acromioclavicular dislocation (Tossy III). The operative technique includes
      suturing of the coracoclavicular and acromioclavicular ligaments and
      stabilization of the clavicle with resorbable, 10-mm coracoclavicular PDS
      banding. Six patients received primary resection of the lateral end of the
      clavicle due to significant injury of the AC joint cartilage. Forty-two patients
      with an average follow-up of 6.1 years were evaluated clinically using the UCLA
      and Constant-Murley Score, as well as subjective grading. Additional radiological
      assessment was performed in 36 cases. Excellent or good clinical results were
      obtained in 97.6%, with 85.7% being free of pain. All patients with primary
      resection of the lateral end of the clavicle had no pain. The incidence of
      postoperative complications was low (one deep wound infection with removal of the
      PDS band, three secondary dislocations). Post-traumatic arthritis developed in
      14.7% of the patients. In those cases of acute grade III AC joint dislocations
      where operative treatment is indicated, this technique provides excellent results
      with a low complication rate.

PMID- 8737583
TI  - [Bite wounds and their characteristic position in trauma surgery management].
AB  - Bite wounds have a special position in traumatology because of their high
      complication rate compared to similar soft tissue wounds caused by other reasons.
      The authors report in a retrospective study about the results of 525 patients
      with bite wounds. In 98 (18.7%) cases the wounds were sutured primarily after
      surgical revision when there was no sign of infection. Antibiotic therapy (a
      combination of amoxicillin and clavulan acid) was given to 109 patients (20.8%)
      who had infected wounds or who were at greater risk for infection (e.g.,
      extremely large wounds, large hematoma). Antibiograms were only made when the
      wounds had already been infected. The total infection rate came to 11.8%, with
      5.2% infected facial bites, 11.3% lower extremity, 18.6% upper extremity and
      18.8% hand bite wounds. The infection rate after primary suture was 10.2% (3.2%
      at the face, 18.8% at the upper extremity and 25% each in the hand and the lower
      extremity). The average time period from the trauma to the first medical
      treatment amounted to 11 h in the infected wounds and 2 h in the non-infected
      ones. Cat bites became infected in 37.5%, dog bites in 14.9%.

PMID- 8737584
TI  - [Injuries of the cervical spine. Diagnosis and surgical treatment].

PMID- 8737585
TI  - [Traumatic rupture of the inferior thyroid artery].
AB  - We report a rare case of traumatic aneurysma of the inferior thyroid artery,
      which occurred after a minor life-threatening trauma. The lesion was diagnosed
      during an angiographical examination, performed because of hemodynamic
      instability of the patient. For therapy, the lesion was ligated and excised.

PMID- 8737586
TI  - [Orthopedic Research Society and American Academy of Orthopedic Surgeons.
      Congresses of a superlative genre. 42nd Annual Meeting Orthopedic Research
      Society (ORS), 17-22 February 1996 and 63rd Annual Meeting American Academy of
      Orthopedic Surgeons (AAOS), 22-26 February 1996, Atlanta].

PMID- 8737587
TI  - [Do we still need a blood-free field?].

PMID- 8737588
TI  - Medical, economic, and regulatory factors affecting point-of-care testing. A
      report of the conference on factors affecting point-of-care testing,
      Philadelphia, PA 6-7 May 1994.
AB  - On 6-7 May 1994, the National Academy of Clinical Biochemistry sponsored a
      conference on point-of-care testing (POCT) in Philadelphia, PA. Several other
      organizations including the American Association for Clinical Chemistry, the
      Centers for Disease Control and Prevention, the Clinical Laboratory Management
      Association, the National Laboratory Training Network Eastern Area Resource
      Office, and Thomas Jefferson University co-sponsored the program, which brought
      together approximately 225 healthcare professionals involved in the decision
      making processes of implementing and overseeing POCT. These individuals included
      clinical chemists, medical technologists, clinicians, pathologists, nurse
      managers, respiratory therapists, laboratory and hospital administrators, and
      manufacturers of point-of-care devices. The conference focused primarily on the
      critical care setting, but some attention was given to the more general patient
      setting. The panelists assessed POCT from four perspectives: (1) medical aspects,
      (2) delivery options for achieving rapid turn-around time, (3) the economics of
      the different delivery options, and (4) legislative, regulatory, and legal
      issues. At the completion of the meeting, areas of agreement and disagreement
      were summarized. In addition, areas requiring further research and
      standardization were delineated. The impact of the conference on laboratory
      practices was evaluated by means of a questionnaire sent to hospital-based
      healthcare personnel approximately 6 months after the meeting.

PMID- 8737589
TI  - Evaluation of multicomponent fluorimetric analytical data by use of partial least
      squares calibration. Application to the determination of codeine and ephedrine in
      urine.
AB  - A partial least-squares calibration (PLS) method for the simultaneous
      spectrofluorimetric determination of acetylsalicylic acid, codeine and ephedrine
      is proposed. The use of PLS for the multicomponent spectrofluorimetric
      determination is demonstrated by analysing synthetic mixtures. Analyte mixtures
      can be resolved even in the presence of strongly overlapped fluorescence signals.
      The method was validated by subjecting experimental data to exhaustive
      statistical analysis. The proposed method was applied to the simultaneous
      determination of the three drugs in synthetic mixtures with a urine matrix. The
      concentration ranges considered are 1.56-10.92 and 25-100 micrograms/ml for the
      codeine-ephedrine mixture, and 0.8-3.2, 0.1-0.5 and 1.6-4.8 micrograms/ml for the
      acetylsalicylic acid-codeine-ephedrine mixture. The analytical results were quite
      good in all cases.

PMID- 8737590
TI  - Defective hepatobiliary leukotriene elimination in patients with the Dubin
      Johnson syndrome.
AB  - The Dubin-Johnson syndrome (DJS) is characterized by a hereditary conjugated
      hyperbilirubinemia and a typical dark pigment accumulation in liver parenchymal
      cells. In the present study the renal excretion of leukotrienes in five patients
      with histologically established DJS and five age- and sex-matched healthy
      subjects was investigated. Endogenous urinary leukotrienes were separated by high
      performance liquid chromatography and subsequently quantified by immunoassays and
      gas chromatography-mass spectrometry. Patients with DJS excreted significantly (P
      < 0.01) greater amounts of cysteinyl leukotriene, LTE4 (8-fold), the omega
      oxidation product omega-carboxy-LTE4 (15-fold) and the beta-oxidation metabolite
      omega-carboxy-tetranor-LTE3 (26-fold) into urine than healthy controls. These
      results imply that in DJS leukotriene elimination into bile is defective, leading
      to a compensatory renal leukotriene elimination and a typical excretion pattern
      of urinary leukotriene metabolites. Analysis of endogenous urinary leukotrienes
      seems to be a new approach to the noninvasive diagnosis of this disease.

PMID- 8737591
TI  - Effect of prednisone on protease activities and structural protein levels in rat
      muscles in vivo.
AB  - To further elucidate the biochemical mechanism by which the corticosteroid
      prednisone induces differential changes in muscle mass (via altered protein
      synthesis/degradation rates) in normal or degenerating muscle tissues, we have
      determined the activity of a range of proteolytic enzyme types, together with
      levels of muscle structural proteins, in five innervated and denervated muscle
      types from control and drug treated rats. In both normal and wasting muscles, the
      activity of many protease types was substantially down-regulated following
      treatment with prednisone; however, accompanying net decreases in muscle mass
      were observed (although the structural protein composition of muscles was
      unaltered following drug treatment). We conclude that whilst overall rates of
      protein degradation in both normal and degenerating muscle may be reduced (via
      protease down-regulation) following prednisone treatment, the effect of the
      latter in reducing protein synthesis rates must be proportionately greater (even
      in actively degenerating tissue). Thus, the data do not support the hypothesis
      that the beneficial effect of prednisone in maintaining muscle mass in
      pathological tissues (e.g., Duchenne muscular dystrophy (DMD)) operates
      principally via down-regulation of protease action/protein catabolism.

PMID- 8737592
TI  - Lithogenicity of human bile is reduced by freezing and thawing.
AB  - We examined the effects of freezing and thawing upon the nucleation time and the
      distribution of cholesterol between micelles and vesicles in 9 human gallbladder
      and 7 hepatic biles. The nucleation time was significantly longer after freezing
      when compared to fresh samples (22.4 +/- 2.6 vs. 7.4 +/- 1.9 days, respectively).
      Concomitantly, a substantial shift of cholesterol from vesicles to micelles was
      noted, with the proportion of vesicular cholesterol decreasing from 26.5% +/-
      6.0% in fresh biles to 8.6% +/- 2.3% after freezing. These effects were observed
      in all types of human biles, regardless of origin, cholesterol saturation or
      initial presence of cholesterol crystals, and were most notable after the first
      week of freezing. The decrease in vesicular cholesterol in all biles and the
      increase in nucleation time of gallbladder biles correlated with the time the
      samples had been in a frozen state. It is concluded that the lithogenic
      properties of human bile are not maintained during storage at -20 degrees C.
      Freezing results in a shift of cholesterol from vesicles to micelles and reduces
      the tendency of cholesterol to crystallize from bile samples.

PMID- 8737593
TI  - Reference intervals for some serum biochemical markers of bone metabolism in
      Kuwait.
AB  - Using the Hitachi 717 Selective Multichannel analyser, we established reference
      intervals for serum albumin (37-9 g/l); measured serum calcium (2.14-2.54
      mmol/l); corrected serum calcium (2.25-2.60 mmol/l); serum phosphate (0.74-1.60
      mmol/l); and alkaline phosphatase (47.0-289.6 U/l) in the Kuwaiti population. The
      mean concentrations of calcium and phosphate decreased with increasing age in
      both sexes except for a sudden increase in women at about menopause. Although
      there was a skewed distribution of alkaline phosphatase in both sexes there was a
      significant increase in enzyme activity in women after the age of 50 years. Using
      corrected serum calcium we found that 15% of women in the reproductive age group
      in Kuwait had hypocalcaemia.

PMID- 8737594
TI  - Serum neuron specific enolase (S-NSE) reference interval evaluation by time
      resolved immunofluorometry compared with a radioimmunoassay.
AB  - The serum neuron specific enolase (S-NSE; EC 4.2.1.11) reference interval was
      evaluated by DELFIA (Wallac) in 161 healthy blood donors and the method compared
      with the S-NSE RIA assay (Pharmacia). The DELFIA assay total analytical variation
      coefficient (CV%) was between 3.7% and 6.6%., the RIA CV% 7.6% to 13.1%. Late
      centrifugation (after hours) increased the variation as a result of contamination
      with blood cells. Log transformation into a gaussian distribution was selected by
      Box-Cox analysis and tested by two models: the gauss-distribution and the Refval
      transformation. The 95% reference intervals and corresponding 90% confidence
      intervals were: female 2.9-9.6 micrograms/l (2.6-3.2 and 8.5-10.7) micrograms/l
      and male 3.4-11.7 micrograms/l (3.0-3.8 and 10.2-13.2 micrograms/l). Mean values
      were significantly different (P < 0.001), female 5.3 (4.9-5.6), male 6.3 (5.8
      6.7) micrograms/l. The serum NSE levels were analysed with both methods in a
      population of 110 patients. The results were significantly correlated
      (coefficient, 0.9896; r, 0.99; P < 0.0001-two tailed). For high S-NSE values (>
      150.0 micrograms/l) differences between the methods exceeded the mean difference
      + 2S.D., while low concentrations were interconvertible. Maximal diagnostic
      efficacy was 0.91 for both assays, in DELFIA 17.2-23.9 micrograms/l and for RIA
      17.2-21.9 micrograms/l. Identical sensitivity, specificity, discriminative power
      score, and likelihood ratio were found. The two methods are consequently
      interconvertible.

PMID- 8737595
TI  - Production and characterization of monoclonal antibodies against L-carnitine:
      radioimmunologic assays for L-carnitine determination.
AB  - Monoclonal antibodies against L-carnitine have been produced and characterized.
      These antibodies have been found to specifically bind L-carnitine and, with
      different affinities, other carnitine-related compounds. No binding was observed
      with choline or acetylcholine. These antibodies have been used to measure L
      carnitine in biological samples and serum. Data obtained demonstrate that, in
      biological samples, by using radiolabelled carnitine, it is possible quickly to
      detect small amounts of carnitine. The high specificity of the test is clearly
      demonstrated.

PMID- 8737596
TI  - Serum alkaline phosphatase activity during zinc deficiency and long-term
      inflammatory stress.
AB  - A decrease in serum zinc can be caused by a real zinc deficiency but can also be
      caused by an apparent zinc deficiency, e.g. in inflammatory stress. The aim of
      this study was to evaluate the diagnostic power of serum alkaline phosphatase
      (AP) activity in the discrimination between pathophysiologic states of "real" and
      "apparent" zinc deficiency. A decrease in serum zinc was induced in growing and
      adult rats, by providing a diet low in zinc and by causing inflammatory stress.
      AP activity was determined using reagents low or enriched in zinc. Serum AP was
      decreased in zinc-deficient adult rats (P < 0.01). In zinc-deficient growing rats
      AP activity was not different from normal rats but AP activity decreased rapidly.
      In the same growing rats a significant difference was found in AP activities
      determined using buffers low and enriched in zinc (P < 0.001) between both groups
      of rats. After inducing inflammatory stress a decrease in AP activity (P < 0.01)
      and serum zinc (P < 0.001) was seen during the first few days. After the initial
      phase of inflammation AP activity normalized, serum zinc showed a rise which
      after correction for the decrease in serum albumin reached the level of the
      control rats. A difference in AP activity in buffers low and enriched in zinc was
      observed only during the first few days after induction of inflammatory stress (P
      < 0.001). Probably the method of measurement of the difference in enzyme
      activity, using buffers low and enriched in zinc, can be used as an indication
      for zinc deficiency in situations with changing AP enzyme concentrations. AP
      activity is decreased during the initial phase of inflammatory stress due to a
      decrease in serum zinc.

PMID- 8737597
TI  - Comparison of proline endopeptidase activity in brain tissue from normal cases
      and cases with Alzheimer's disease, Lewy body dementia, Parkinson's disease and
      Huntington's disease.
AB  - Neuronal death associated with plaque and tangle formation characteristic of
      Alzheimer's disease (AD) may result from an underlying defect of intracellular
      protein catabolism. In an attempt to identify the proteolytic enzyme types
      responsible for aberrant protein processing, we have composed the levels of
      activity of proline endopeptidase in brain tissue samples (grey/white matter)
      from frontal, parietal, temporal and occipital lobes, from normal control cases,
      and cases with AD, Lewy body dementia (LBD), Parkinson's disease (PD) and
      Huntington's disease (HD). The activity of proline endopeptidase was
      significantly reduced in AD to approximately 65% of that of corresponding control
      tissue-this is of note since previous biochemical analyses have in general failed
      to detect altered activity of other protease types in AD tissues. However, this
      relatively selective reduction in proline endopeptidase activity in AD tissue (in
      terms of protease types investigated) is not specific for disease type, since
      activity was also reduced (65%-70% of control) in tissue samples from LBD, PD and
      HD cases. The data suggest that reduction in proline endopeptidase activity may
      be a characteristic of a generalized process of neurodegeneration. Although the
      precise cellular function of this enzyme in normal/ pathological tissues remains
      to be determined, the question arises as to whether pharmacological strategies
      designed to enhance proline endopeptidase activity in brain tissue may improve
      patient outcome in the above disorders.

PMID- 8737598
TI  - Kinetic nephelometric determination of albumin produced by rat hepatocytes in
      culture.
AB  - A kinetic immunonephelometric method for the determination of albumin produced by
      rat hepatocytes in culture is described. This assay is simple, rapid and
      sensitive. The methodology allows detection of 0.7 mg/l albumin in 200
      microliters of culture medium. Within-run precision CVs for three levels of
      concentrations were under 1.0% and between-day precision CVs were under 4.1%. The
      range of measurement obtained using appropriately diluted samples was 1.2 to 74
      mg/l. The rabbit IgG fraction to rat albumin used in this method did not cross
      react with albumin from cow, allowing the use of fetal calf serum in the medium.
      The method described can thus be used easily for the assessment of albumin
      synthesis in cellular studies using isolated hepatocytes.

PMID- 8737599
TI  - Alterations of erythrocyte morphology and lipid composition by
      hyperbilirubinemia.
AB  - Morphology and membrane lipid composition of erythrocytes from neonates
      (jaundiced and healthy) and adults (before and after incubation with bilirubin)
      were studied. The morphological index, expressing the relative proportions of the
      different stages of cell distortion, and the membrane cholesterol, phospholipids
      and cholesterol/phospholipids molar ratio, were determined. In jaundiced neonates
      a significant increase in the morphological index (P < 0.01) was found. After
      incubation with bilirubin, adult erythrocytes also showed an increase in the
      morphological index (P < 0.01). Hemolysis occurred under these conditions, and
      the red cell ghosts obtained (vesicles) showed a rounded morphology. Higher
      cholesterol/phospholipid ratio and lower phospholipid content were found in
      jaundiced neonates compared with healthy babies (P < 0.05) and adults (P < 0.01),
      as well as in the cells (P < 0.05) and vesicles (P < 0.01) obtained after
      bilirubin incubation. Bilirubin cytotoxicity may occur in a stepwise manner:
      deposition of bilirubin in membrane produces echinocytosis, which is followed by
      disintegration of the lipid bilayer with loss of phospholipids from the membrane.

PMID- 8737600
TI  - The effects of tert-butyl hydroperoxide on human erythrocyte membrane ion
      transport and the protective actions of antioxidants.
AB  - The oxidising actions of tert-butyl hydroperoxide (tBH) (0-3 mmol/l) on human
      erythrocyte membrane ion transport have been studied using measurements of 86Rb+
      influx. Ouabain and bumetanide were used to distinguish Rb+ flux via the sodium
      pump (Na,K-ATPase), Na,K,2Cl cotransporter and through residual membrane
      permeability. The protective actions of antioxidants and related molecules
      (vitamin E, vitamin E acetate, Trolox, butylated hydroxytoluene (BHT) and
      dithioerythritol (DTE) were studied. The effects of tBH were concentration
      dependent and the mean residual (ouabain and bumetanide insensitive) Rb+
      permeability was increased by a factor of 8.5 (S.E.M. 2.2, n = 15) by a 5-min
      exposure to 2 mmol/l tBH. This action was almost completely prevented by co
      incubation with Trolox or BHT, and partially prevented by the presence of vitamin
      E or DTE. Incubation with 2 mmol/l tBH for 5 min increased intracellular Na+ by a
      factor of 1.8 (S.E.M. 0.1, n = 8) and reduced intracellular K+ by a factor of
      0.93 (S.E.M. 0.03, n = 8). These effects were prevented by Trolox and partially
      prevented by vitamin E, whereas DTE and vitamin E acetate were ineffective.
      Incubation with 2 mmol/l tBH for 5 min reduced the mean apparent sodium pump Vmax
      by 43% (S.E.M. 4, n = 8). This effect was completely prevented by Trolox and
      partially prevented by vitamin E. Vitamin E acetate had no effect. The mean
      bumetanide-sensitive Rb+ influx via the Na,K,2Cl cotransporter was reduced by 30%
      (S.E.M. 8.7, n = 25) by a 5-min exposure to 2 mmol/l tBH. This action was
      variable and no significant actions of the antioxidants studied could be
      demonstrated. This study suggests that tBH-mediated oxidative damage occurs from
      a hydrophilic site and involves increased non-selective membrane cation
      permeability and inhibition of specific transport systems.

PMID- 8737601
TI  - Plasma thiols, cognitive function and ageing.

PMID- 8737602
TI  - The use of calcein acetomethylester (AM)-labelled polymorphonuclear cells in a
      polycarbonate filter chemotaxis assay.

PMID- 8737603
TI  - Adenylosuccinate lyase deficiency and disorders of saccharide metabolism;
      experience with combined screening test.

PMID- 8737604
TI  - CHD in the elderly: knowledge for clinicians and researchers.

PMID- 8737605
TI  - Coronary heart disease risk factors in older persons.
AB  - In most Western nations, coronary heart disease (CHD) is the leading cause of
      death and one of the most important causes of physical disability in persons over
      65 years of age. The importance of traditional CHD risk factors has been well
      documented in middle-aged populations, whereas their role in older populations is
      still under debate. This paper reviews the epidemiologic evidence from
      observational studies and randomized clinical trials that established risk
      factors for CHD predict level of risk of CHD, and identify high risk individuals
      among older men and women. Hypertension and cigarette smoking have been clearly
      associated with an increased risk of CHD events, and their modification has been
      proven to be highly effective in the primary and secondary prevention of CHD in
      older persons. For other highly prevalent risk factors, such as lipid
      abnormalities, obesity and physical inactivity, evidence of an independent
      association with CHD risk has been demonstrated by the majority of observational
      studies. However, definitive proof from controlled clinical trials of the
      beneficial effects of their modification is still lacking in the older
      population. The role of estrogen replacement therapy in the primary and secondary
      prevention of CHD in old women is still an open question. In evaluating the
      impact of these risk factors in older persons, elements such as comorbidity,
      frailty, and age-related changes in risk profile should also be taken into
      consideration. Given the complexity of the relationship between risk factors and
      multiple disease statuses, other important outcomes, such as osteoporosis,
      cancer, falls and physical disability, should be considered when evaluating the
      risks and benefits of risk factor modifications in older persons.

PMID- 8737606
TI  - Inotropic agents in older patients with chronic heart failure--current
      perspectives.
AB  - Until recently, inotropic therapy has been regarded as the most direct remedy for
      the left ventricular systolic dysfunction that often underlies the development of
      heart failure. Nevertheless, all the agents with significant inotropic properties
      that have been evaluated to date (such as beta adrenergic stimulants,
      phosphodiesterase inhibitors, and high-dose vesnarinone) showed significant
      increases in mortality with long-term administration. However, it is noteworthy
      that the participants in trials to evaluate inotropic therapy were not
      representative of geriatric heart failure patients for age, gender, and
      comorbidity. Thus, results from these studies must be interpreted cautiously when
      treatment for chronic heart failure must be applied to elderly subjects. At
      present, digitalis is the only inotropic agent recommended for long-term
      treatment, because it improves symptoms and prevents disease progression through
      neurohormonal and baroreceptor mechanisms; nevertheless, its long-term safety is
      still undetermined. The role of low-dose vesnarinone, pimobendan and ibopamine,
      which share neurohormonal, rather than inotropic, mechanisms of action, is still
      under investigation. Pending the definition of these issues, ACE-inhibitors and
      diuretics remain the mainstay of therapy for chromic heart failure.

PMID- 8737607
TI  - Differential effects of reduced muscle use (hindlimb unweighting) on skeletal
      muscle with aging.
AB  - The changes in hindlimb muscle mass, fiber area and contractile tension that
      occurred with two weeks of reduced weight-bearing (HU) were of greater magnitude
      in 6-month-old as opposed to 36-month-old rats. The pattern of change following
      HU for young and old animals differed, which may indicate that multiple
      mechanisms are responsible for the observed changes. The majority of old rats had
      difficulty with ambulation following unweighting, suggesting that the functional
      consequences of reduced weight-bearing are greater in old than in young animals.
      One hour of weight-bearing during HU attenuated the decline in SOL fiber atrophy,
      muscle mass and Po, but had no apparent effect on the GAST, PL or EDL. The
      reduction in Po with HU was not due, except for the old PL, to changes at the
      neuromuscular junction.

PMID- 8737608
TI  - Erythrocytic calpain-calpastatin system in Alzheimer's disease.
AB  - Calpains, calcium activated neutral proteases (CANP), and calpastatin (CAST),
      their specific inhibitor, are involved in the proteolysis of amyloid precursor
      protein (APP), which is thought to be abnormal in Alzheimer's disease (AD). We
      studied the CANP/CAST system in erythrocytes of 14 clinically probable AD
      patients, 11 young and 14 old controls. CANP and CAST activities in the control
      subjects significantly correlated with increasing age; old controls showed a
      significant increase in CANP and CAST activities compared to young controls.
      Values of CANP and CAST activities in AD patients were similar to those of young
      controls. The physiological gage-related increase in proteolysis seems to be lost
      in AD patients, and this could play a role in the pathogenesis of the disease.
      However, due to the overlap of results between patients and controls, we could
      not reliably differentiate the healthy from the disease state on the basis of
      erythrocytic CANP/CAST activity.

PMID- 8737609
TI  - Exercise in frail elderly men decreases natural killer cell activity.
AB  - Six frail male outpatients 70 years and older deemed at risk for fall, but not
      suffering from serious medical problems nor receiving immune-altering drugs,
      received an exercise intervention of increasing strenuousness for 60 minutes 3
      times a week for 3 months in comparison with 7 controls having no intervention.
      Psychosocial and immunologic assessments were made at baseline (Time 1), and
      after 6 (Time 2) and 12 (Time 3) weeks of physical conditioning. Cytotoxic
      activity of natural killer (NK) cells significantly decreased during the course
      of the study, in spite of transient exercise-induced increases at times 2 and 3.
      Despite the many known benefits of exercise, this report suggests its possible
      adverse effects on NK cell cytotoxicity in the very frail elderly. Mild
      overexertion in frail old people may be clinically significant in view of the now
      recognized role of NK cells in the prevention of metastasis.

PMID- 8737610
TI  - Infection surveillance and antibiotic utilization in a community-based skilled
      nursing facility.
AB  - To survey the types of suspect infections, the antibiotic utilization and the
      patterns of antibiotic resistance among bacterial pathogens in a community
      Skilled Nursing Facility (SNF), we conducted a 20-month prospective observational
      surveillance program comprising all 585 patients admitted to a 149-bed private
      community SNF. Data were collected form medical charts, laboratory reports and
      nurses reports. Overall, 41% of the patients developed at least one presumptive
      nosocomial infection, and 54% of the patients received one or more antibiotic
      treatments. The overall presumptive nosocomial infection rate was 7.2 per 1000
      patient days. The most common sites of presumptive nosocomial infection were the
      urinary tract (38%) and the respiratory tract (28%). The most common pathogens
      overall were E. coli (25%). Antibiotic groups used most frequently were the
      quinolones (22% of prescriptions). Thirty-nine percent of the Staphylococcus
      aureus isolates associated with suspected infections were resistant to
      methicillin, and of these 94% were also resistant to ciprofloxacin. Most of the
      resistant S. aureus isolates were from indwelling catheter-associated with UTIs.
      Infections associated with quinolone resistant strains of gram-negative bacilli
      were infrequent. No epidemiologic evidence of nosocomial clustering was apparent.

PMID- 8737611
TI  - Influence of age, exercise, and dietary restriction on oxidative stress in rats.
AB  - This study was undertaken to investigate the effects of exercise, dietary
      restriction (DR) and aging on the formation of reactive oxidant species (ROS),
      antioxidant defenses, and membrane fluidity. Test were performed on hepatic
      microsomes, mitochondria, and cytosol from 9- and 20-month-old male Fischer 344
      rats, which were divided into four groups: ad libitum fed, sedentary (AS);
      restricted, sedentary (RS); ad libitum fed, exercised (AE); and restricted,
      exercised (RE). Results show that both exercise and DR suppressed microsomal ROS
      production, but not mitochondrial ROS production, which increased with age in all
      groups. Exercise and DR increased catalase and glutathione peroxidase (GSH-Px)
      activities and maintained cytosolic ascorbic acid concentration at high levels.
      Exercise led to significantly higher levels of cytosolic glutathione (GSH).
      Activity of cytosolic superoxide dismutase (SOD) remained unchanged, whereas
      glutathione-s-transferase (GST) activity significantly increased with DR. The
      fluidity of the mitochondrial membrane from exercised and DR rats deteriorated
      less with age than the membrane from AS rats. Exercise alone was found to improve
      fluidity, but was more effective when coupled with DR. These results suggest for
      the first time that the combination of exercise training and DR is the most
      effective means of preserving membrane fluidity and suppressing microsomal ROS
      production.

PMID- 8737612
TI  - Swallowing and the duration of the hyoid movement in normal adults of different
      ages.
AB  - Normal swallows were examined using ultrasound imaging. Durational data of the
      hyoid movement were obtained from frame-by-frame analysis. The duration of the
      hyoid movement of three consecutive unstimulated (= dry) swallows was compared to
      that of stimulated (= wet) swallows in 120 subjects equally distributed among
      both sexes and four different age groups. Dry swallows proved to be longer than
      wet ones, and the duration of both types increased with age. The first dry
      swallow was invariably shorter than the third one; no such difference was noted
      with the wet swallows. With increasing age, the oral phase was more frequently
      accompanied by extra hyoid gestures, and the total number of swallows produced
      during a 10-second period was reduced in the elderly. These differences probably
      do not indicate pathology, but may be explained by changes in oral sensitivity,
      and subclinical oral-motor changes which occur in normal subjects with increasing
      age.

PMID- 8737613
TI  - The geriatrician in 1996--a viewpoint from Switzerland.
AB  - The aging of populations represents a tremendous challenge for the 21st century,
      all the more since it is known that men are more often confronted with periods of
      disability in later life than in other periods of their life span. To meet this
      concern, actions should be taken in the medical field and in this regard, the
      geriatrician has an essential role to play. Geriatrics, as an innovative
      discipline, should become a widely-recognized and strengthened speciality on the
      academic plane, also through promoting high-level research, on which high-quality
      teaching in turn depends. There is a need, therefore, to arm family doctors,
      because they are in charge of following up the population's aging; indeed, they,
      better than anyone else, know the difference between normal aging and pathology,
      and thereby are the very first to make interventions aimed at facilitating the
      aging process.

PMID- 8737614
TI  - Comparison of an enzyme-linked immunosorbent assay vs radioimmunoassay for
      measuring serum progesterone at low levels.
AB  - Reports have suggested a correlation between low serum progesterone (P) levels
      prior to human chorionic gonadotropin (hCG) administration and increased
      pregnancy rates in patients undergoing in vitro fertilization (IVF) patients. We
      have published two opposite conclusions, dependent upon the methodology used.
      Pregnancy rates were higher when P by radioimmunoassay (RIA) was < 1 ng/mL, but
      no increase in pregnancy rates were found when P was measured by the same
      company's non-isotopic assay. To test if the lack of correlation was attributable
      to the P method, sera from IVF patients were assayed by two methods, RIA and
      enzyme linked immunosorbent assay (ELISA). There was 81.8% agreement between
      methods. Further studies are needed to determine the importance of low P;
      however, if non-isotopic methods are used, the IVF center should carefully
      determine the accuracy of their assay in the low range.

PMID- 8737615
TI  - Urinary excretion of relaxin after estradiol treatment of postmenopausal women.
AB  - The influence of estradiol treatment on the urinary excretion of relaxin, a
      hormone in earlier years only found during pregnancy and presently associated
      with functions in the cardiovascular system, was investigated in postmenopausal
      women. Thirteen postmenopausal women were treated with transdermal estradiol and
      12 women with oral estradiol for 4 weeks. A new radioimmunoassay for human
      relaxin (rec-hRLX-2) was used. With transdermal, but not with oral
      administration, a significant increase of urinary relaxin excretion was
      registered. Further experiments are necessary to elucidate the source of urinary
      relaxin and its role in the hormone replacement therapy of postmenopausal women.

PMID- 8737616
TI  - Laparoscopic treatment of ovarian endometrioma. One year follow-up.
AB  - Thirty-six women with ultrasonographic diagnosis of ovarian endometrioma
      (bilateral in nine of them), have been treated laparoscopically. After the
      surgical procedure the patients were assigned to one of the following regimes: Gn
      RH-a for 3 months, oral contraceptives if they wanted to avoid pregnancy, or
      nothing. The follow-up consisted in 1-3-6-12 months ultrasound. The first
      recurrences were observed at the 6-month ultrasound with an overall recurrence
      rate after 12 months of 11%. Improvement of pain symptoms occurred in 87% of the
      patients and fertility rate was 45%.

PMID- 8737617
TI  - Study of the electromechanical activity of the uterus. Experimental study.
AB  - The uterine electromechanical activity was studied in 12 mongrel bitches. The
      uterus was exposed under general anesthesia, and 2 electrodes were sutured to its
      serosa. The electric activity was recorded for 30 minutes/day for 10 days.
      Simultaneous electric and mechanical activity (registered by a 4 F catheter
      connected to a pressure transducer) was also studied without and with uterine
      distension by a balloon. The electric activity was further recorded after
      performing uterine annular myotomy proximal and distal to the electrodes and
      between them. Pacesetter potentials (PPs) were registered from the 2 electrodes,
      having identical frequency and regular rhythm by the 2 electrodes, and were
      consistent in the individual dog on all test days. Action potentials (APs)
      followed PPs randomly and were associated with increase in uterine pressure.
      Balloon distension of the uterus effected increased PP and AP frequency. Annular
      uterine myotomy led to PP and AP disappearance distally but not proximally to
      myotomy. In conclusion, the study demonstrates that the uterus possesses electric
      activity represented by PPs which spread caudally. APs seem to be contractile
      waves. Recording of the electromechanical activity of the uterus may be of
      diagnostic significance in uterine disorders.

PMID- 8737619
TI  - Relationship of early follicular phase sera follicle stimulating hormone and
      luteinizing hormone levels as measured by a radioimmunoassay and an enzyme-linked
      immunosorbent assay to number of oocytes retrieved.
AB  - A study was performed to see if the level of serum follicle stimulating hormone
      (FSH) or luteinizing hormone (LH) obtained in the early follicular phase could
      predict the number of oocytes retrieved following in vitro fertilization (IVF).
      For each patient the sera FSH and LH were measured by both an enzyme-linked
      immunosorbent assay (ELISA) and a radioimmunoassay (RIA) method. With the ELISA
      method when early follicular phase serum FSH was < or = to the group median (9.0
      mIU/mL) 16.5 oocytes were retrieved vs 6.7 when FSH was greater than the median.
      Comparable values using the median of the RIA assay were 17.5 vs 8.1 oocytes.
      Similar analysis for serum LH failed to show any relationship between baseline LH
      and the number of oocytes retrieved. This study thus demonstrates that at least
      one non-isotopic method is equal to a specific RIA method in distinguishing good
      from average or poor responders.

PMID- 8737618
TI  - Prediction of the need for insulin therapy in pregnant women with impaired
      gestational glucose tolerance (IGGT).
AB  - OBJECTIVE: Our aim was identify pregnant women with impaired gestational glucose
      tolerance (IGGT) at risk for more severe gluco-metabolic alterations who could
      require subsequent insulin therapy during pregnancy. METHODS: We studied 78
      pregnant women with IGGT after a 100 g glucose oral tolerance test. Patients were
      divided into two groups based on a cut-off value of a 15% reduction from normal
      values of the glucose load. Sixty-three patients had at least one value above
      this cutoff point, while 15 had all residual values below the cut off. All
      patients were put on a diet and glycemia reassessed: those who showed pre
      prandial blood glucose higher than or equal to 90 mg/dl and/or 2-h post-prandial
      higher than or equal to 120 mg/dl underwent insulin therapy. We matched the
      presence of at least one residual value in the oral glucose tolerance test above
      the limit used with the subsequent need for insulin treatment. RESULTS: The
      presence of at least one residual value above the "-15%" cutoff in the glucose
      tolerance test was associated with high risk (positive predictive value 79%),
      whereas normality of the residual values indicated low risk (negative predictive
      value 80%), of insulin need during the rest of pregnancy. CONCLUSIONS: Pregnant
      women with IGGT definitely do not have a normal metabolic condition, sometimes
      even requiring diet and insulin treatment. From our results, the need for more
      accurate monitoring and insulin treatment may be predicted by simply looking at
      the residual values in the glucose tolerance test.

PMID- 8737620
TI  - Effects of cyclic therapy with intranasal carbocalcitonin in healthy spontaneous
      postmenopausal women.
AB  - Carbocalcitonin spray administered for 12 months at a daily dosage of 80 U MRC
      according to five schedules has been tested on 150 normal spontaneous
      postmenopausal women for its influence on bone mineral density (BMD), bone
      metabolism and osteoarticular pain. BMD was monitored before and at the end of
      treatment in comparison with BMD of untreated control women. Metabolic markers
      (serum alkaline phosphatase, serum osteocalcin and urinary hydroxyproline) were
      also evaluated before and during treatment (at the 9th or 10th month of
      treatment). Osteoarticular pain was assessed by an analogic visual scale.
      Intranasal carbocalcitonin, administered according to cyclic schedules at a high
      frequency dosage, was able to maintain bone mass only in the earlier
      postmenopausal women. BMD percent increase after 12 months of treatment was 1.10
      and 1.31 in women with low (< 0.870 mg/cm2) and high baseline BMD (> or = 0.870
      mg/cm2), respectively. In advanced menopause the maintaining effect of
      carbocalcitonin on BMD seemed evident only if the baseline bone mass was lower
      than the BMD of the age matched control group. At least six months of
      treatment/year is necessary for effective therapy. Both systemic and local
      tolerance were optimal. No significant side-effects were detected.

PMID- 8737621
TI  - Vaginal endometriosis. Two case reports and review of the literature on rare
      urogenital sites.
AB  - The authors present two rare cases of vaginal endometriosis. Moreover, the
      literature regarding other sites of low genital tract involvement is reviewed.

PMID- 8737622
TI  - Human papilloma virus--H.P.V. condyloma. Current studies in diagnosis, treatment
      and prognosis.
AB  - Since 1982, in the Republic of Panama, we evaluated 5,400 women who showed the
      oncological risk (R.O.) in 59% and in which the participation of pure or
      associated HPV was 87.6%. The incidence of the HPV in our female population is
      52% with a prevailing age of 20-40 years.

PMID- 8737623
TI  - The diagnosis of benign uterine pathology using transvaginal
      endohysterosonography.
AB  - Twenty-nine women believed to be affected with benign uterine pathologies
      underwent transvaginal hysterosonography insertion of a physiological solution
      into the cervical cavity by means of a catheter positioned in the cervical canal.
      This new technique, due to the acoustic window created by the fluid, made it
      possible to find: one cervical polyp, six endometrial polyps, one endometrial
      synechia, five submucosa myomas and one uterine malformation, the presence of
      which, with traditional ultrasonography can only be suspected. The subsequent
      hysteroscopic check-up confirmed the high diagnostic reliability of
      hysterosonography which is also easy to carry out, safe and costs little.

PMID- 8737624
TI  - An obstetric and neonatal study on unplanned deliveries before arrival at
      hospital.
AB  - OBJECTIVE: To establish the prevalence of unplanned deliveries before arrival at
      a big metropolitan hospital and to determine the demographic characteristics of
      the group of women at risk of delivering before arrival. DESIGN: A random case
      control study. Each baby born before arrival and its mother were compared to the
      next baby born in the same Department. SUBJECTS: All babies born before arrival
      at the Department of Obstetrics and Gynecology, University "La Sapienza" in a 10
      yr. period (Jan 1983-Dec 1993). RESULTS: Of 27,274 consecutive deliveries in the
      study period, 22 (0.8%) babies were born before arrival at hospital. Of the 22
      women who delivered before arrival, 16 were Italian, 5 were considered nomad (no
      fixed address) and one was a Polish tourist. No statistical difference was found
      between groups regarding maternal age, parity, gestational age, birth weight and
      immediate delivery complications. No mortality cases were observed in the study
      or control group. Neonatal stay in the neonatal ward was longer in the study
      group (6.5 vs 3.5 days, P < 0.001). Hypothermia was the highest morbidity (P <
      0.001) and neonatal complications were more prevalent in babies delivered before
      arrival than in-born babies (P < 0.001). CONCLUSIONS: Delivery before arrival to
      hospital does not seem to carry a higher neonatal mortality risk. However, the
      prevalence of complications was higher in such babies, with hypothermia being the
      highest morbidity.

PMID- 8737625
TI  - Acute leukemia and pregnancy. Case report.
AB  - In this case report we describe a case of acute myeloid leukemia (AML; FAB M4)
      diagnosed in a 27-year-old female at the 20th week of gestation. After informed
      consent, the patient chose to undergo anti-leukemic treatment without therapeutic
      abortion. Complete remission was obtained following standard chemotherapy for AML
      (doxorubicin, cytosin-arabinoside, 6-thioguanine). The patient successively
      underwent an autologous bone marrow transplant (ABMT). No fetal malformation was
      observed. Urgent cesarean section was necessary at the 29th gestational week
      because of the onset of foetal sufferance. Fourteen months after diagnosis and
      seven months after ABMT the patient died due to relapse of AML. The child is
      presently 3.5 year old and well. In our opinion, the care of a pregnant woman
      with acute leukemia is feasible and it needs a multi-specialist effort that is
      easier to be achieved in a tertiary care institution.

PMID- 8737626
TI  - In vitro effects of the novel anti-epileptic agent vigabatrin on alanine
      aminotransferase and aspartate aminotransferase activities in rat serum.
AB  - The in vitro effects of vigabatrin (CAS 60643-86-9, MDL 71,754) on alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) activities were
      examined in rat serum. Initially, vigabatrin (30-100 micrograms/ml) produced a
      concentration-dependent decrease in ALT activity at 100 micrograms/ml or more
      after 15 min incubation with the rat serum. AST activity, in contrast, was
      unaffected by concentrations up to 1,000 micrograms/ml. Next, treating the rat
      serum with vigabatrin (30-300 micrograms/ml) for up to 5 h produced a
      concentration- and time-dependent decrease in ALT activity. On the other hand, a
      decrease in AST activity was observed only after incubation with the highest
      concentration of vigabatrin for 3 h or more. Finally, an investigation was made
      on the antagonistic effect of L-alanine, a natural substrate for ALT, on the
      vigabatrin-induced decrease in ALT activity to elucidate possible mechanisms
      underlying the inhibitory effect of vigabatrin on ALT activity. L-alanine,
      depending on its concentration, countered the effects of vigabatrin (100
      micrograms/ml) at a 10- or 100-fold higher molar ratio than vigabatrin. These
      findings suggest that vigabatrin favorably decreases ALT activity by blocking the
      L-alanine binding site of enzymes.

PMID- 8737627
TI  - Nocturnal psychometric assessment of the hypnotic activity of low and normal
      doses of brotizolam.
AB  - The hypnotic activity of acute doses of 0.125 mg and 0.250 mg brotizolam (CAS
      57801-81-7, Lendormin) was compared in a double-blind randomised placebo
      controlled study. Forty-nine healthy female volunteers aged between 23 and 44
      years were enrolled. Trial medication was administered sublingually at 9:15 p.m.
      and 9:30 p.m., respectively. The nocturnal investigations continued until 2:30
      a.m. A final examination was performed in the morning after breakfast. Every 30
      min mood was measured by visual analogue scales. A computerised psychometric test
      (CDT) over 8 min was undertaken in order to measure continuous attention under
      short-term memory load. The Digit Symbol Substitution Test (DSST) was performed
      every hour. The CDT was not evaluable due to significant baseline differences. A
      statistically significant sedative effect in the DSST was already found 30 min
      after administration of 0.250 mg brotizolam, while the effect of 0.125 mg
      brotizolam just failed to reach the threshold of significance. Both treatments
      showed equivalent efficacy at 0.5, 1.5 and 2.5 h after administration. After 3.5
      and 4.5 h there was no statistically significant difference between placebo and
      0.125 mg brotizolam. After 4.5 h 0.250 mg brotizolam still showed significant
      hypnotic activity compared to placebo and 0.125 mg brotizolam. No treatment
      effects on mood were apparent according to the visual analogue scales.
      Furthermore, no hangover effects were detected for any of the parameters
      measured. The pharmacodynamic results confirmed the duration of action of more
      than 4.5 of h 0.250 mg brotizolam found in earlier studies and suggest that 0.125
      mg is as effective as 0.250 mg with regard to sleep onset disturbances but has a
      shorter duration of action.

PMID- 8737628
TI  - Effects of 6-(3-dimethylaminopropionyl)forskolin hydrochloride on energy
      metabolism in dog hearts in situ.
AB  - The effect of NKH477 (6-(3-dimethylaminopropionyl)forskolin hydrochloride, CAS
      138605-00-2) [formula: see text], a newly developed forskolin derivative, on
      mechanical function, carbohydrate metabolism and energy metabolism was examined
      in the dog heart, and compared with that of dobutamine. Intravenous injection of
      NKH477 (10 or 30 micrograms/kg) or dobutamine (1 or 3 micrograms/kg) increased
      the maximum rate of rise of left ventricular pressure (LVdP/dtmax), producing a
      positive inotropic effect. The duration of the effect of NKH477 was longer than
      that of dobutamine. In addition, NKH477 (10 or 30 micrograms/kg) increased heart
      rate (positive chronotropic effect). Nevertheless, neither NKH477 (10 or 30
      micrograms/kg) nor dobutamine (1 or 3 micrograms/kg) modified the tissue levels
      of adenosine triphosphate, adenosine diphosphate, adenosine monophosphate,
      creatine phosphate and lactate. Glycolytic flux (as expressed by the ratio of
      ([glucose-6-phosphate] + [fructose-6-phosphate]) / [fructose-1,6-diphosphate])
      and redox state (as expressed by the ratio of [lactate] / [pyruvate]) in the
      myocardial cells were not influenced by NKH477 (10 or 30 micrograms/kg) or
      dobutamine (1 or 3 micrograms/kg). These results suggest that NKH477 produces
      both positive inotropic and positive chronotropic effects, while it does not
      interfere with the myocardial energy and carbohydrate metabolism.

PMID- 8737629
TI  - Characterization of sulfation patterns of beef and pig mucosal heparins by
      nuclear magnetic resonance spectroscopy.
AB  - Though differing only slightly in their degrees of sulfation, heparin
      preparations from pig mucosa and those from beef mucosa have consistently
      different 13C- and 1H-NMR spectra, which provide useful fingerprints for
      distinguishing the two types of heparin. Integrated areas of NMR signals
      associated with minor, undersulfated sequences (assigned by comparison with mono
      dimensional spectra of selectively desulfated heparins and by analysis of two
      dimensional spectra of heparins prepared from pig and beef mucosa) permit
      quantitation of differences in sulfation patterns. Undersulfation of pig mucosal
      heparins at position 6 of the hexosamine units, determined by 13C-NMR and
      expressed as percent glucosamines nonsulfated at C6 referred to total
      glucosamines, is substantially lower for pig mucosal heparins than for beef
      mucosal heparins (16.9-21.7% vs 36.7-40.7%; average values: 18.6% vs 40.3%). By
      contrast, undersulfation at position 2 of the iduronic acid units, determined by
      1H-NMR and expressed as percent nonsulfated iduronic acid referred to total
      (sulfated + nonsulfated) iduronic acid is significantly higher for pig mucosal
      preparations (9.6-13.5% vs 2.1-2.7%; average values: 12.7% vs 2.3%). Pig mucosal
      heparins also have a significantly higher content of 3-O-sulfated glucosamine
      units, which are markers for the active site of heparin for antithrombin-III.

PMID- 8737630
TI  - Investigation of the efficacy of oxerutins compared to placebo in patients with
      chronic venous insufficiency treated with compression stockings.
AB  - The aim of this study was to investigate, if the the combined treatment of
      compression stockings and drug treatment with oxerutins (O-(beta-hydroxyethyl)
      rutosides, Venoruton) provides additional benefit for patients with chronic
      venous insufficiency (CVI) compared to compression treatment alone. Oxerutins
      belong to the group of oedema protective agents and possess anti-exudative and
      membrane protective activity. A total of 133 female patients with CVI grade II
      participated in this double-blind, randomised, multi-centre, parallel-group study
      with two treatment groups. The whole study lasted for 19 weeks, and consisted of
      a one week placebo run-in phase, 12 weeks treatment phase, followed by a 6 weeks
      treatment-free follow-up period. All patients received a basis compression
      therapy that consisted of standard compression stockings. In order to standardise
      initial fitting of stockings in this multi-centre setting, stockings were fitted
      after one week of standard diuretics starting at baseline and then stockings were
      worn for the following 11 weeks. Patients were randomised to receive oxerutins (2
      x 500 mg daily) or matching placebo. Leg volumes (water displacement) and
      associated subjective symptoms (visula analogue scale) were measured during a
      placebo run-in period at enrolment (week - 1) and half a week later (week - 1/2),
      at baseline week 0), at 4, 8, 12 weeks on treatment, and again after a 3- and 6
      weeks treatment-free follow-up. The primary efficacy criterion, the area under
      the baseline from week 0 to week 18 (AUB0-18) of leg volume changes, as
      measurement of the global change of leg oedema during the study, resulted in a
      superior reduction of -5589 ml.d for the combined treatment with oxerutins
      compared to -2101 ml.d for placebo (p = 0.012). The mean change of leg volume
      compared to baseline after 12 weeks of treatment was -63.9 ml for stockings and
      oxerutins, and -32.9 ml for the patients who received stockings and placebo (p <
      0.05). Oxerutins showed a prolonged effect in the follow-up phase compared to
      placebo, with mean AUB values for week 12 to week 18 of -1769 ml.d versus -133
      ml.d (p < 0.01). The study demonstrated that the combined therapy of compression
      stockings and drug treatment with oxerutins is significantly superior in reducing
      leg oedema resulting from chronic venous insufficiency compared to compression
      treatment alone.

PMID- 8737631
TI  - Comparative clinical efficacy and tolerability of oxerutins and horse chestnut
      extract in patients with chronic venous insufficiency.
AB  - Oxerutins (O-(beta-hydroxyethyl)rutosides, HR, Venoruton) and horse chestnut
      extract (HCE) are active principles of first priority for the pharmacological
      treatment of chronic venous insufficiency (CVI). The efficacies of both compounds
      were shown in numerous, double-blind, randomized, placebo controlled clinical
      trials. Besides the direct comparison of the two compounds the aim of the study
      was to investigate the initial dose/maintenance dose concept for HR. 137 female,
      postmenopausal patients with CVI II finished the study according to protocol.
      Following one week placebo run-in the patients were treated either with 1000 mg/d
      HR, 600 mg/d HCE or 1000 mg/d for 4 weeks and than with 500 mg/d HR within the
      initial dose/maintainance dose concept for 12 weeks and observed for further 6
      weeks. A main confirmative criterion was the volume reduction of the leg.
      Subjective criteria were descriptively evaluated. HR (1000 mg/d) was proven to be
      equivalent or better, reducing the leg volume (AUB0-18) by -5273 +/- 11418 ml.d
      compared to -3187 +/- 10842 ml.d under HR (1000 mg/d and 500 mg/d), and -3004 +/-
      7429 ml.d under HCE-treatment. Both compounds exhibit a substantial carry-over
      effect. The maintenance posology of HR is able to stabilize the therapeutic
      obtained under initial dose conditions.

PMID- 8737632
TI  - Investigation of the therapeutic equivalence of different galenical preparations
      of O-(beta-hydroxyethyl)-rutosides following multiple dose peroral
      administration.
AB  - Oxerutins (O-(beta-hydroxyethyl)-rutosides, HR, Venoruton) are available in
      different releasing galenical formulations for the treatment of chronic venous
      insufficiency (CVI). In order to investigate the biopharmaceutical relevance of
      the releasing properties of the galenical forms the therapeutic efficacy between
      the commercially available forms was investigated (500 mg sustained release film
      tablets, 300 mg sustained release film tablets, 300 mg normally releasing
      capsules) in comparison to an aqueous solution and placebo. In total 100 female
      patients with CVI grade II participated. The study was carried out following a
      randomized, placebo controlled design with parallel treatment groups. Following a
      two-week run-in phase patients were treated for 12 weeks with different
      posologies of HR (2 x 1/d 500 mg, 3 x 1/d 300 mg, 1 x 1000 mg/d as aqueous
      solution). Main criterion was the reduction of leg volume following 12 weeks
      treatment. Subjective criteria were descriptively evaluated. All four HR
      treatments were significantly superior to placebo (p < 0.0008). The different
      posologies had no influence on the efficacy. The therapeutic efficacy is
      independent of the in vitro rate of release. The available forms are regarded as
      bioequivalent.

PMID- 8737633
TI  - Dialysis clearance of buflomedil in hemodialysed patients.
AB  - Buflomedil (CAS 55837-25-7, Fonzylane) is a peripherally vasoactive drug which
      improves nutritional blood flow in ischaemic tissue of patients with peripheral
      vascular disease by the way of an increase of perfusion in the microcirculation.
      Ten hemodialysed patients with chronic renal failure treated with intravenous
      infusion of 400 mg of buflomedil during 4 h of dialysis were included in the
      first study. This study was carried out to determine the dialysis plasma
      clearance and the amount of drug dialysed during the first intravenous
      administration of buflomedil. The dialysis clearance calculated from the amount
      recovered in dialysate was (mean +/- SD) 25.4 +/- 25.6 ml/min. The drug recovery
      resulting from hemodialysis represented a small fraction of the dose (< or = 5%).
      A second study was carried out to determine the accumulation of buflomedil in
      chronic hemodialysed patient. The drug concentration were measured before and at
      the end (4 h) of the infusion of buflomedil in six other patients maintained on
      intermittent hemodialysis (3 per week) for 4 weeks. The average Cmin and Cmax
      were stable during the 12 successive dialyses (mean +/- SD intervals were between
      0.36 +/- 0.53 and 0.66 +/- 0.79 microgram/ml for Cmin and between 5.15 +/- 2.19
      and 7.37 +/- 1.76 micrograms/ml for Cmax), showing no trend of accumulation of
      buflomedil. These results agree with the pharmacokinetics of the drug which is
      mainly metabolised in the liver and has a low renal clearance. Dialysis is unable
      to modify significantly the plasma concentration of the drug in regularly
      dialysed patients.

PMID- 8737634
TI  - Oxatomide and derivatives as inhibitors of mediator release from a mast cell
      model. Structure-activity relationships.
AB  - A series of benzimidazolone and benzimidazole analogues of the antiallergic drug
      oxatomide (1-?3-[4-(diphenylmethyl)-1-piperazinyl]propyl?-1,3-dihydro-2H-
      benzimidazol-2-one, CAS 60607-34-3) [formula: see text], was evaluated for
      inhibiting the release of the performed mediator beta-hexosaminidase from the rat
      basophilic leukemia (RBL-2H3) cell line. Activation of the cells was induced by
      antigen, or by the calcium ionophore A23187 (calcimycin) in combination with or
      without the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). For the
      active compounds, inhibition of exocytosis was found with all triggers, with the
      antigen trigger being somewhat more sensitive. This indicates that the compounds
      influence several steps in the signal transduction route leading to exocytosis.
      The activity of the compounds is not totally aspecific as small structural
      changes strongly affect the inhibiting activity. Introduction of a chlorine
      substituent at the 6-position of the benzimidazolone group results in loss of
      activity. There does not seem to be a significant activity difference between the
      benzimidazolone and benzimidazole analogues. Analogues with n < 3, n > 5 or a
      branched alkyl chain between the piperazinyl and the benzimidazol(on)e moiety
      lose inhibitory activity. Secretion of the newly formed mediator arachidonic acid
      and its metabolites was affected by the compounds comparable to the effect on the
      release of beta-hexosaminidase. The anti-allergic activity did not correlate with
      the histamine H1-receptor antagonistic activity.

PMID- 8737635
TI  - Direct detection of the antioxidant activity of a new flavonic derivative using
      the chemiluminescence method.
AB  - The antioxidant potential of a new water soluble flavonic derivative, namely
      theophylline rutoside (TR-1722) has been tested using the chemiluminescence
      method. The method is based on the oxidative degradation of luminol by the
      hydrogen peroxide in Tris-HCl-buffer, when reactive species of oxygen are being
      obtained: O2-., HO., 1O2, and allows for the capability of substances to inhibit
      the free radical processes in this test system to be quantified and hence for
      their antioxidant properties in respect to a standard substance (in our case
      quercetin) to be compared. The results obtained reveal that TR-1722 has
      antioxidant action comparable to that of quercetin, the highest efficacity being
      registered at the concentration of 2 mumol/l, the conditions being: H2O2 16,2
      mmol/l; luminol 2 mumol/l, in Tris-HCl buffer 20 mmol/l, pH 8.3. The antioxidant
      potential of TR-1722 is also maintained when the conditions of the system are
      modified, that is, the concentration of the hydrogen peroxide, the intensity of
      the action being dependent on the hydrogen peroxide concentration, but no direct
      proportionality is registered.

PMID- 8737636
TI  - New analgesics derived from the phencyclidine analogue thienylcyclidine.
AB  - Several derivatives of thienylcyclidine (1-[1-(2-thienyl)cyclohexyl]piperidine,
      CAS 1867-65-8, TCP) were synthesized and characterized. The compounds were
      evaluated for analgesic agonism in mice using tail-flick test as a model for
      antinociceptive activity. The most potent compounds are 7 and 11, which are about
      twice as active as the standard pethidine. The influence of naloxone on the
      antinociceptive activity of these compounds is also reported. The present
      pharmacological data are discussed and compared with those previously reported
      for structurally related phencyclidine analgesics.

PMID- 8737637
TI  - Effect of acetylsalicylic acid, paracetamol, caffeine and a combination of these
      substances on the renal prostaglandin E2, 6-keto-prostaglandin F1 alpha, water,
      creatinine and electrolyte excretion of the rat.
AB  - The aim of the study was to investigate the effect of acetylsalicylic acid (CAS
      50-78-2, ASA), paracetamol (CAS 103-90-2) and caffeine (CAS 58-08-2) and a
      combination of these substances on the renal prostaglandin excretion of rats
      loaded with water. In addition to the effects on the renal excretion of
      prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha),
      the effect on the electrolyte, creatinine and water excretion was measured. Even
      in low doses ASA led to a dose-dependent reduction in the renal PGE2 and 6-keto
      PGF1 alpha excretion. In oral doses up to 200 mg/kg paracetamol did not have any
      effect on the renal prostanoid excretion. In the combination it did not change
      the effect of ASA on the prostaglandin excretion. Caffeine caused a marked dose
      dependent increase in the PGE2 excretion. The effect of caffeine on the renal 6
      keto-PGF1 alpha excretion was less marked. In combination with ASA, with and
      without the addition of paracetamol, caffeine reduced the inhibitory effect of
      ASA on the excretion of arachidonic acid metabolites. The values for the renal
      prostaglandin excretion did not show any clear correlation with the other
      parameters of diuresis.

PMID- 8737638
TI  - Effects of acetylsalicylic acid, paracetamol and caffeine and a combination of
      these substances on kidney glutathione levels.
AB  - Following preliminary tests in which rats proved to be fairly insensitive to the
      depletory effect of paracetamol (CAS 103-90-2) on kidney glutathione levels, old
      male mice from a strain exhibiting particular susceptibility to paracetamol were
      investigated in respect of the comparative effects of paracetamol,
      acetylsalicylic acid (CAS 50-78-2, ASA) and caffeine (CAS 58-08-2), and a
      combination of these substances, on kidney glutathione levels. Additionally, the
      effects of paracetamol and ASA on hepatic glutathione in mice were also measured.
      When administered separately at oral doses of 150-600 mg/kg both paracetamol and
      ASA produced dose- and time-dependent depletion of kidney glutathione
      concentrations in the mice. The effect of ASA at a given dose was weaker than
      that of paracetamol. Caffeine showed only a very weak and transient depletory
      effect up to an oral dose of 60 mg/kg. The effects of the combined administration
      of paracetamol and ASA on kidney glutathione levels were only additive in nature.
      The administration of caffeine did not increase the reduction in kidney
      glutathione levels produced by the combination of paracetamol and ASA. The
      reduction in hepatic glutathione induced in the mice by paracetamol was
      considerably more pronounced than that observed in the kidneys. ASA, on the other
      hand, did not affect glutathione in the mouse liver at those doses which had led
      to a reduction in kidney glutathione levels.

PMID- 8737639
TI  - Confirmation of efficacy of etofibrate against peripheral atherosclerosis in non
      human primates which model human lesion types I-VII.
AB  - In dyslipidemic or hyperlipidemic patients etofibrate (CAS 31637-97-5, active
      principle of Lipo-Merz-retard) improves plasma lipoprotein profiles by reducing
      low density lipoprotein cholesterol and triglycerides. Experimentally, it also
      promotes fibrinolysis and thrombolysis and reduces the susceptibility of
      lipoproteins to oxidative stress. In order to investigate the possible efficacy
      of etofibrate on atherosclerosis, a study in African Green Monkeys was performed.
      To accelerate atherogenesis, balanced groups of adult male Vervetes
      (Cercopithecus aethiops) were fed an atherogenic diet, with and without
      etofibrate, while negative controls received a prudent diet. Total dietary risk
      exposure was 38 months, with etofibrate treatment during the final 27 months. The
      etofibrate dose achieved plasma concentrations of clofibric acid comparable to
      the one achieved clinically. Necropsy demonstrated lesions equivalent to human
      atherosclerosis types I-VII, which were compared between treatments both
      macroscopically and microscopically. Peripheral atherosclerosis was significantly
      less frequent after etofibrate treatment than in positive controls. In aortas,
      etofibrate probably ameliorated atherogenesis, as defined by proliferation of
      smooth muscle and foam cells, and accumulation of cholesterol crystals. Effective
      reduction of plasma cholesterol by etofibrate was confirmed. In conclusion, anti
      atherogenic efficacy of etofibrate was demonstrated in a non-human primate model
      of accelerated atherogenesis. The results on peripheral atherosclerosis confirm
      the preliminary clinical data in patients suffering from peripheral vascular
      occlusion.

PMID- 8737640
TI  - Studies of the K(ATP) channel opening activity of the new dihydropyridine
      compound 9-(3-cyanophenyl)-3,4,6,7,9,10-hexahydro-1,8-(2H,5H)-acridined ione in
      bladder detrusor in vitro.
AB  - The potassium (K+) channel opening activity of ZM244085 (9-(3-cyanophenyl)
      3,4,6,7,9,10-hexahydro-1,8-(2H,5H)-acridined ione, CAS 149398-59-4), a novel
      dihydropyridine (DHP), was ascertained. In a set of functional assays, its
      mechanoinhibitory effect on myogenic activity of guinea pig bladder detrusor
      muscles, either mildly or highly depolarized with 15 or 80 mmol/l KCl, was
      measured. ZM244085 had negligible effect on the tone of the detrusor contracted
      with 80 mmol/l KCl but reduced the myogenic activity induced with 15 mmol/l KCl
      (IC50=4.2 +/- 0.4 mumol/l). Glibenclamide, an ATP-sensitive K+ (KATP) channel
      blocker, competitively antagonized this action of ZM244085 with a pA2 value of
      7.6. This functional profile of ZM244085 is similar to that of the prototypic K+
      channel opener cromakalim but stands in contrast to that of typical DHP Ca2+
      channel blockers such as nifedipine and nimodipine. The membrane potential of the
      guinea pig detrusor, recorded with intracellular microelectrodes, was
      hyperpolarized 6.8 +/- 3.1 mV by ZM244085 (10 mumol/l). This hyperpolarization
      was completely blocked by glibenclamide but not affected by apamin (10 mumol/l),
      a toxin blocking specifically small conductance and Ca2+ dependent K+ (SKCa)
      channels. ZM244085 (10 mumol/l) increased the whole cell KATP current in isolated
      guinea pig detrusor cells by 8.8 +/- 2.5 pA, but failed to activate large
      conductance and Ca2+ dependent K+ (BKCa) channels in excised inside-out membrane
      patches from those cells. The results from these studies showed that ZM244085 is
      a K+ channel opener which activates predominantly KATP channels in vitro to relax
      bladder detrusors.

PMID- 8737641
TI  - Bioavailability of fluoride administered as sodium fluoride or sodium
      monofluorophosphate to human volunteers.
AB  - This paper reports a reassessment of the bioavailability of fluoride from
      monofluorophosphate (MFP, CAS 10163-15-2). It was prompted by recent work from
      this laboratory reporting that, following an oral dose of MFP, a fraction of the
      drug appears in plasma bound to globulins forming a previously undetected
      compartment of non-diffusible fluoride. The presence of protein-bound MFP in
      plasma after the intake of this drug hinders its straightforward comparison with
      NaF (CAS 7681-49-4). After an oral of NaF, all plasma fluoride is diffusible.
      After intake of MFP, on the other hand, plasma contains diffusible fluoride and
      protein-bound fluoride during the 6-8 h following intake. The area under the
      curve of total plasma fluoride for MFP (1540 +/- 117 mumol.min/l) doubles that of
      NaF (811 +/- 52 mumol.min/l p < 0.001). On this basis, in agreement with findings
      previously reported for the rat, it is concluded that the bioavailability of
      fluoride for MFP doubles that of NaF.

PMID- 8737642
TI  - [Antibacterial action of clindamycin in chronic, recurrent tonsillitis].
AB  - After oral administration of 300 mg Sobelin, the efficacy and pharmacological
      kinetics of clindamycin (CAS 18323-44-9) were analysed in 35 patients with
      recurrent tonsillitis. Minimal inhibitor concentration (MIC) and minimal
      bactericidal concentration (MBC) have been evaluated for 120 strains. MIC and MBC
      for 91.7% of the strains amounted to 0.25 micrograms/ml. Concentrations of
      antibiotics in the serum were higher than 0.25 micrograms/ml after 12 h, i.e.
      higher than the minimal inhibitory concentration. The established free and
      efficient portion of clindamycin in the serum which is not bound to plasma
      proteins shows that a clear bacteriostatic effect is achieved up to 6 h after
      application of the antibiotic. The concentration in the tissue of the tonsils was
      0.6-0.8 micrograms/g after 7-9 h indicating that sufficient MIC values were
      achieved. The free portion of the antibiotic in the tissues after 9 h also
      reached the MIC of germs. Hence clindamycin is considered to be an efficient
      antibiotic in the management of acute exacerbation of recurrent tonsillitis. Due
      to serum- and tissue levels of the tonsils administration of 300 mg of the test
      drug is indicated three times daily.

PMID- 8737643
TI  - Susceptibility of Helicobacter pylori and Candida spp. to the east African plant
      Terminalia spinosa.
AB  - Trees of the genus Terminalia have long been used in the traditional medicine of
      Kenya (East Africa). In an ethnopharmacological approach, extracts of the stem
      bark of Terminalia spinosa were investigated for antibacterial and antifungal
      activity. The extracts were active against Helicobacter pylori, with the
      following minimum inhibitory concentrations (MIC): MIC50 of 125 mg/l, MIC90 of
      250 mg/l, and MIC-range of 62.5-500 mg/l. Yeasts of the genus Candida showed a
      similar susceptibility. The results indicate that the plant if a source of
      antimicrobial compounds with therapeutic potential.

PMID- 8737644
TI  - Effect of basic fibroblast growth factor on wound healing in healing-impaired
      animal models.
AB  - The effect of basic fibroblast growth factor (bFGF) on wound healing was studied
      in healing-impaired animal models such as metabolic diseases (obesity and
      diabetes), infection, steroid treatment, malnutrition and chronic liver failure.
      bFGF treatment resulted in an acceleration of wound healing in an almost same
      dose range regardless of impairment causes or animal species used. The beneficial
      effects of bFGF on wound healing were suggested to be due to its potent
      angiogenesis and granulation tissue formation activities, leading to a rapid
      reepitherialization of the wound. In addition, the findings that bFGF promoted
      healing in infection wound and burn wound of diabetic mice, and burn wound of
      dietary-restricted rats indicated its ability to accelerate wound contraction,
      another important process of wound closure.

PMID- 8737645
TI  - Proband and parent assistance in identifying relatives for cystic fibrosis
      carrier testing.
AB  - To identify, contact, and offer free cystic fibrosis (CF) carrier education,
      testing, and genetic counseling to the first, second, and third degree relatives
      of individuals with CF, study personnel contacted probands or the parents of
      minor probands requesting assistance in identifying relatives. We requested
      family pedigrees, including names, addresses, and phone numbers and if necessary
      a saliva sample for determination of the specific CF mutations in the family. Two
      hundred three families of 220 probands being followed at a large CF clinic in the
      Southeastern United States were eligible for inclusion in the study. Of the 203
      families 109 (53.7%) assisted by providing contact information on relatives and,
      when necessary, a saliva sample for mutation analysis. An additional 33 (16.4%)
      agreed to assist but did not provide either or both contact information or saliva
      samples. Sixty-one (30.1%) declined to provide assistance. Thirteen percent of
      the probands/parents wanted to talk with relatives before providing contact
      information. A logistic regression model predicting proband/parent assistance is
      provided. This study suggests that the active outreach method used here to
      identify at risk relatives to offer them CF carrier testing resulted in somewhat
      lower proband or parent assistance than reported by other similar approaches. The
      strengths and weaknesses of this approach, including comments by probands and
      parents on the method, are discussed.

PMID- 8737646
TI  - A new case of Klippel-Trenaunay-Weber (KTW) syndrome: evidence of autosomal
      dominant inheritance.
AB  - Most cases of KTW syndrome are sporadic. However, in a few, other family members
      have some clinical manifestations of the syndrome, and an autosomal dominant mode
      of inheritance has been suggested. In this paper we present a family with an
      affected child who has large skin hemangiomata, overgrowth of the right leg, and
      severe heart defects. Her mother has a large capillary hemangioma on the left
      side of back and has developed severe varicosities in both lower extremities. The
      maternal grandmother developed severe varicosities in her legs at a young age.
      The clinical signs found in the mother and maternal grandmother represent a
      milder phenotype and might be explained as variable expressivity of the syndrome.
      The family tree supports autosomal dominant inheritance.

PMID- 8737647
TI  - Bilateral porencephaly, cerebellar hypoplasia, and internal malformations: two
      siblings representing a probably new autosomal recessive entity.
AB  - We report on 2 sibs with bilateral porencephaly, absence of the septum
      pellucidum, and pancerebellar hypoplasia including absence of the vermis. Situs
      inversus and tetralogy of Fallot was present in one, and an atrial septal defect
      in the other. This constellation of findings is discussed against the background
      of familial porencephalies and schizencephalies, familial cerebellar hypoplasias,
      and asplenia/polysplenia syndromes. It is concluded that the described
      constellation of findings constitutes a new entity of probably autosomal
      recessive inheritance.

PMID- 8737648
TI  - Non-mosaic tetrasomy 9p in a liveborn infant with multiple congenital anomalies:
      case report and comparison with trisomy 9p.
AB  - Tetrasomy of the short(p) arm of chromosome 9 has been reported in few cases.
      Most of these children present with microbrachycephaly, wide forehead,
      hypertelorism, lowset, malformed ears, beaked noses, and micrognathia. Additional
      anomalies include short neck, congenital heart disease, genital abnormalities,
      multiple limb defects, hypotonia, and early death.

PMID- 8737649
TI  - Juvenile myoclonic epilepsy in chromosome 6p12-p11: locus heterogeneity and
      recombinations.
AB  - We recently analyzed under homogeneity a large pedigree from Belize with classic
      juvenile myoclonic epilepsy (JME). After a genome wide search with 146
      microsatellites, we obtained significant linkage between chromosome 6p markers,
      D6S257 and D6S272, and both convulsive and EEG traits of JME. Recombinations in
      two affected members defined a 40 cM JME region flanked by D6S313 and D6S258. In
      the present communication, we explored if the same chromosome 6p11
      microsatellites also have a role in JME mixed with pyknoleptic absences. We
      allowed for heterogeneity during linkage analyses. We tested for heterogeneity by
      the admixture test and looked for more recombinations. D6S272, D6S466, D6S294,
      and D6S257 were significantly linked (Zmax > 3.5) to the clinical and EEG traits
      of 22 families, assuming autosomal dominant inheritance with 70% penetrance.
      Pairwise Zmax were 4.230 for D6S294 (theta m = f at 0.133) and 4.442 for D6S466
      (theta m = f at 0.111). Admixture test (H2 vs. H1) was significant (P = 0.0234
      for D6S294 and 0.0128 for D6S272) supporting the hypotheses of linkage with
      heterogeneity. Estimated proportion of linked families, alpha, was 0.50 (95%
      confidence interval 0.05-0.99) for D6S294 and D6S272. Multipoint analyses and
      recombinations in three new families narrowed the JME locus to a 7 cM interval
      flanked by D6S272 and D6S257.

PMID- 8737650
TI  - CVS-exposed limb deficiency defects with or without other birth defects:
      presentation of six cases born during a period of nine years.
AB  - We report on six cases with CVS-exposed limb-"reduction" defects born in our
      hospital during a period of 9 years (1986-1994). Four cases were associated with
      other birth defects. One had an oromandibular-limb hypogenesis syndrome with a
      cleft lip and jejunal atresia, a second had an oromandibular-limb hypogenesis
      (Hanhart) syndrome, a third had severe flexion deformity at the hips and
      hyperextension at the knees with meconium peritonitis and intestinal obstruction,
      and a fourth had Poland anomaly. Detailed clinical descriptions, prenatal
      diagnosis, photographs, and radiographs are presented. Our presentation adds to
      the information on severe limb abnormalities after CVS and suggests CVS-exposed
      limb defects may be associated with other birth defects resulting from vascular
      insufficiency or intrauterine compression. We suggest that detailed post-CVS
      sonographic followups are necessary for each CVS-exposed case to identify not
      only the possible fetal limb reduction, but also vascular disruption-type
      malformations and compressive deformities.

PMID- 8737651
TI  - Characterization by fluorescence and electron microscopy in situ hybridization of
      a double Y isochromosome.
AB  - A patient with mixed gonadal dysgenesis and Y isochromosomes i(Y) is described.
      Lymphocyte cultures from peripheral blood contained a high proportion of 45,X
      cells and several other cell lines with two different marker chromosomes (mars).
      These markers had either a monocentric (mar1) or a dicentric appearance (mar2).
      Following high-resolution GTG, RBG, QFQ, and CBG bandings, five cell lines were
      identified; 45,X/46,X,+mar1/46,X,+mar2/47,X,+mar1x2/47,X,+mar2x 2. The
      percentages were 66/6/26/1/1%, respectively. Chromosome banding analyses were
      insufficient for characterization of the markers. In situ hybridization of
      specific probes for the Y centromere and its short arm showed, both in
      fluorescence and electron microscopy (EM), two different Y rearrangements. Mar1
      is an isochromosome for the short arm i(Yp) and mar2 is a dicentric which was
      shown by EM to be a double isochromosome Yp, inv dup i(Yp). The breakpoint
      producing mar1 is within the centromere and the one producing mar2 is within one
      of the short arms of the Y isochromosome. The findings of different cell
      populations in peripheral blood lymphocytes indicate the postzygotic instability
      of this i(Yp).

PMID- 8737652
TI  - Identical twin discordance for the Brachmann-de Lange syndrome revisited.
AB  - The only known twin pair evidently discordantly affected for the BDLS (Brachmann
      de Lange syndrome) and who had been considered monozygotic (MZ) based on blood
      analysis remained a problem because biological zygosity determination needed
      further typing. In this report we review the clinical findings of this pair of
      twins at the age of 20. The use of DNA fingerprinting with three multilocus
      probes, F10, DNF24, and 33.6, allowed us to present evidence of monozygosity with
      a high degree of certainty. The significance of this confirmation of discordance
      in determining the cause of BDLS is discussed. Intensive comparative genomic
      studies of the discordant twin sisters may be useful to unravel the molecular
      genetics of this enigmatic pattern of malformation.

PMID- 8737653
TI  - A-2-->G transition at the 3' acceptor splice site of IVS17 characterizes the
      COL2A1 gene mutation in the original Stickler syndrome kindred.
AB  - Hereditary progressive arthro-ophthalmopathy, or "Stickler syndrome," is an
      autosomal dominant osteochondrodysplasia characterized by a variety of ocular and
      skeletal anomalies which frequently lead to retinal detachment and precocious
      osteoarthritis. A variety of mutations in the COL2A1 gene have been identified in
      "Stickler" families; in most cases studied thus far, the consequence of mutation
      is the premature generation of a stop codon. We report here the characterization
      of a COL2A1 gene mutation in the original kindred described by Stickler et al.
      [1965]. Conformational sensitive gel electrophoresis (CSGE) [Ganguly et al.,
      1993] was used to screen for mutations in the entire COL2A1 gene in an affected
      member from the kindred. A prominent heteroduplex species was noted in the
      polymerase chain reaction (PCR) product from a region of the gene including exons
      17 to 20. Direct sequencing of PCR-amplified genomic DNA resulted in the
      identification of a base substitution at the A-2 position of the 3' splice
      acceptor site of IVS17. Sequencing of DNA from affected and unaffected family
      members confirmed that the mutation segregated with the disease phenotype.
      Reverse transcriptase-PCR analysis of poly A+ RNA demonstrated that the mutant
      allele utilized a cryptic splice site in exon 18 of the gene, eliminating 16 bp
      at the start of exon 18. This frameshift eventually results in a premature
      termination codon. These findings are the first report of a splice site mutation
      in classical Stickler syndrome and they provide a satisfying historical context
      in which to view COL2A1 mutations in this dysplasia.

PMID- 8737655
TI  - EEC syndrome and genitourinary anomalies: an update.
AB  - We report on a large family with the ectrodactyly, ectodermal dysplasia, clefting
      (EEC) syndrome. The clinical manifestations in this family show great
      variability. Specific genitourinary anomalies were found. The propositus with
      micturition problems is discussed in detail. A dysplastic bladder epithelium
      might be the cause of these problems. A remarkable improvement of the complaints
      was achieved upon treatment with synthetic sulfonated glycosaminoglycans.

PMID- 8737654
TI  - Diagnosis of four chromosome abnormalities of unknown origin by chromosome
      microdissection and subsequent reverse and forward painting.
AB  - A molecular cytogenetic method consisting of chromosome microdissection and
      subsequent reverse/forward chromosome painting is a powerful tool to identify
      chromosome abnormalities of unknown origin. We present 4 cases of chromosome
      structural abnormalities whose origins were ascertained by this method. In one
      MCA/MR patient with an add(5q)chromosome, fluorescence in situ hybridization
      (FISH), using probes generated from a microdissected additional segment of the
      add(5q) chromosome and then from a distal region of normal chromosome 5,
      confirmed that the patient had a tandem duplication for a 5q35-qter segment.
      Similarly, we ascertained that an additional segment of an add(3p) chromosome in
      another MCA/MR patient had been derived from a 7q32-qter segment. In a woman with
      a history of successive spontaneous abortions and with a minute marker
      chromosome, painting using microdissected probes from the whole marker chromosome
      revealed that it was i(15)(p10) or psu dic(15;15)(q11;q11). Likewise, a marker
      observed in a fetus was a ring chromosome derived from the paracentromeric region
      of chromosome 19. We emphasize the value of the microdissection-based chromosome
      painting method in the identification of unknown chromosomes, especially for
      marker chromosomes. The method may contribute to a collection of data among
      patients with similar or identical chromosome abnormalities, which may lead to a
      better clinical syndrome delineation.

PMID- 8737656
TI  - Ectodermal dysplasia, Rapp-Hodgkin type in a mother and severe ectrodactyly
      ectodermal dysplasia-clefting syndrome (EEC) in her child.
AB  - We describe a mother with manifestations most consistent with the Rapp-Hodgkin
      type of ectodermal dysplasia and her malformed newborn son with ectrodactyly,
      ectodermal dysplasia, cleft palate, and bilateral cystic and obstructive
      ureteroceles with hydroureters and cystic renal dysplasia as described in the EEC
      syndrome. This observation suggests that the Rapp-Hodgkin type of ectodermal
      dysplasia and EEC syndrome, both defined as autosomal dominant conditions with
      variable expression, may be manifestations of the same mutated gene. We also want
      to emphasize that urogenital anomaly is another hallmark of the EEC syndrome.

PMID- 8737657
TI  - Mosaic tetrasomy 15q25-->qter in a newborn infant with multiple anomalies.
AB  - We describe a premature boy with metopic craniosynostosis, facial anomalies,
      atrial-septal defect, hydronephrosis and flexion contractures of lower limbs, and
      mosaic tetrasomy 15q25-->qter. The extra chromosome material was present in the
      form of an acentric marker. A number of clinical manifestations observed in this
      child were also found in 3 previously reported patients who were trisomic for the
      same part of chromosome 15 and in 2 patients who were tetrasomic for a larger
      segment of 15q.

PMID- 8737658
TI  - Correlation between connexin 32 gene mutations and clinical phenotype in X-linked
      dominant Charcot-Marie-Tooth neuropathy.
AB  - We studied the relationship between the genotype and clinical phenotype in 27
      families with dominant X-linked Charcot-Marie-Tooth (CMTX1) neuropathy. Twenty
      two families showed mutations in the coding region of the connexin32 (cx32) gene.
      The mutations include four nonsense mutations, eight missense mutations, two
      medium size deletions, and one insertion. Most missense mutations showed a mild
      clinical phenotype (five out of eight), whereas all nonsense mutations, the
      larger of the two deletions, and the insertion that produced frameshifts showed
      severe phenotypes. Five CMTX1 families with mild clinical phenotype showed no
      point mutations of the cx32 gene coding region. Three of these families showed
      positive genetic linkage with the markers of the Xq13.1 region. The genetic
      linkage of the remaining two families could not be evaluated because of their
      small size.

PMID- 8737659
TI  - Sex ratios in fetuses and liveborn infants with autosomal aneuploidy.
AB  - Ten data sources were used substantially to increase the available data for
      estimating fetal and livebirth sex ratios for Patau (trisomy 13), Edwards
      (trisomy 18), and Down (trisomy 21) syndromes and controls. The fetal sex ratio
      estimate was 0.88 (N = 584) for trisomy 13, 0.90 (N = 1702) for trisomy 18, and
      1.16 (N = 3154) for trisomy 21. All were significantly different from prenatal
      controls (1.07). The estimated ratios in prenatal controls were 1.28 (N = 1409)
      for CVSs and 1.06 (N = 49427) for amniocenteses, indicating a clear differential
      selection against males, mostly during the first half of fetal development. By
      contrast, there were no sex ratio differences for any of the trisomies when
      comparing gestational ages < 16 and > 16 weeks. The livebirth sex ratio estimate
      was 0.90 (N = 293) for trisomy 13, 0.63 (N = 497) for trisomy 18, and 1.15 (N =
      6424) for trisomy 21, the latter two being statistically different than controls
      (1.05) (N = 3660707). These ratios for trisomies 13 and 18 were also
      statistically different than the ratio for trisomy 21. Only in trisomy 18 did the
      sex ratios in fetuses and livebirths differ, indicating a prenatal selection
      against males > 16 weeks. No effects of maternal age or race were found on these
      estimates for any of the fetal or livebirth trisomies. Sex ratios for
      translocations and mosaics were also estimated for these aneuploids. Compared to
      previous estimates, these results are less extreme, most likely because of larger
      sample sizes and less sample bias. They support the hypothesis that these trisomy
      sex ratios are skewed at conception, or become so during embryonic development
      through differential intrauterine selection. The estimate for Down syndrome
      livebirths is also consistent with the hypothesis that its higher sex ratio is
      associated with paternal nondisjunction.

PMID- 8737660
TI  - Lumpers, splitters, and FGFRs.

PMID- 8737661
TI  - A matter of reading English.

PMID- 8737662
TI  - HZF-3, an immediate-early orphan receptor homologous to NURR1/NOT: induction upon
      membrane depolarization and seizures.
AB  - Nuclear hormone receptors are thought to play important roles in the regulation
      of gene expression in the hippocampus. We report here the isolation of an
      additional member of this superfamily, HZF-3, which is expressed preferentially
      in the rat brain and therein within the hippocampus. HZF-3 cDNA encodes a 66.6
      kDa protein with high homology to the inducible nuclear orphan receptors
      NURR1/NOT and NGFI-B. Like NURR1/NOT and NGFI-B, HZF-3 mRNA accumulates in PC12
      cells subsequent to membrane depolarization. In the rat brain, HZF-3 expression
      is induced following seizures elicited by the chlorinated insecticide lindane.
      The time course of HZF-3 induction by membrane depolarization in PC12 cells and
      seizures in animals is more prolonged than that observed for other immediate
      early genes, such as NGFI-B. Electrophoretic mobility shift assays demonstrated
      HZF-3 to interact specifically with the same DNA target element as NGFI-B: NBRE.
      These results suggest HZF-3 is a member of a distinct family of inducible orphan
      receptors which are likely to display synergistic and/or antagonistic regulatory
      functions in mediating signal-induced transcriptional responses in the nervous
      system.

PMID- 8737663
TI  - Differential distribution of mRNA encoding cAMP-specific phosphodiesterase
      isoforms in the rat brain.
AB  - We studied the distributions of four different cyclic AMP-specific
      phosphodiesterase isoform mRNAs (APDE1-4) and compared them with that of 63 kDa
      calmodulin-stimulated phosphodiesterase (CPDE) in the rat brain by in situ
      hybridization histochemistry using specific radiolabeled oligonucleotides. The
      distribution patterns were unique for all the APDE isoforms examined here.
      Although no significant signals for APDE1 could be detected anywhere in the rat
      brain, all other isoforms were expressed ubiquitously but unevenly and showed
      overlapping distribution patterns. Among all the APDE isoforms studied here,
      APDE3 showed the strongest and the most extensive expression. Its distribution
      pattern implies that it may modulate different cellular processes associated with
      learning and memory. Compared to APDE3, the levels of expression of APDE2 and
      APDE4 were weaker, the latter showing the weakest expression. Our study suggests
      that different isoforms of APDE are expressed together in the same class of
      neurons implying complex interactions among different signaling pathways, thereby
      mediating distinct and specific functions.

PMID- 8737664
TI  - Prolonged alteration in E-box binding after a single systemic kainate injection:
      potential relation to F1/GAP-43 gene expression.
AB  - The presence in hippocampus of a basic helix-loop-helix (bHLH) family of
      transcription factors (TFs) specifically binding in an electrophoretic mobility
      shift assay (EMSA) to the E-box recognition element was established by selective
      blockade of binding both by cold competition and by an antibody to MyoD1, an E
      box TF. Protein source was from a micro-dissected preparation enriched in
      hippocampal granule cells. Specific E-box binding of hippocampal transcription
      factors was significantly reduced in kainate acid (KA) treated animals. This was
      observed at 24 and 72 h, but not before (3, 6 h) or after (96 h). This is the
      first report to our knowledge to study functional regulation of E-box binding
      protein in adult hippocampus. To determine the generality of this E-box
      regulatory event, we studied four other situations, in addition to kainate
      treatment, where axonal growth is known or has been suggested to increase: NGF
      treatment of PC12 cells, unilateral hilar lesions, long-term potentiation after 1
      h, and postnatal rat hippocampal development. In all four cases, decreased E-box
      binding was observed. The recent link of F1/GAP-43 mRNA induction in hippocampal
      granule cells by KA to growth of their axons, the mossy fibers in the adult rat,
      suggests a potential role for the F1/GAP-43 5' flanking promoter region in
      regulating neurite outgrowth. Since in all cases decreased E-box binding preceded
      increased F1/GAP-43 mRNA expression, it is suggested that E-box binding to the
      F1/GAP-43 promoter in hippocampal granule cells could negatively regulate F1/GAP
      43 gene expression. Indeed, analysis of recognition elements on the F1/GAP-43
      gene revealed an arrangement, previously described in other genes, of multiple
      adjacent E-box elements. E-box binding of bHLH transcription factors is likely to
      occur on several different genes in addition to F1/GAP-43. It is, therefore,
      attractive to think that E-box binding is regulated by in vivo activation of the
      adult brain and that this gene regulatory event participates in the orchestration
      of molecular and cellular responses underlying axonal growth.

PMID- 8737665
TI  - Induction of apolipoprotein E mRNA in the hippocampus of the gerbil after
      transient global ischemia.
AB  - B/A4 is the major component of brain amyloid plaque, one of the hallmarks of
      Alzheimer's disease (AD). B/A4 is a product of proteolytic processing of its
      precursor, the Alzheimer amyloid precursor protein (APP). Recently,
      apolipoprotein E (APO-E) has also been shown to be associated with Alzheimer's
      disease pathology because it is localized to plaques and tangles, and the gene
      encoding one of the isoforms of APO-E (E4) is associated with late-onset familial
      and sporadic AD. In addition, APO-E exhibits high affinity for binding to the B
      peptide (B/A4). In this study, we have investigated changes in the steady state
      levels of APP, APO-E, and the astrocyte-specific marker, glial fibrillary acidic
      protein (GFAP) mRNA in the gerbil hippocampal CA1 region after a 10-min period of
      bilateral carotid occlusion-induced forebrain ischemia. Following this insult, we
      observed a loss of 90% of the CA1 neurons by 72 h post-ischemia. The mRNA levels
      on day 1 through day 7 post-ischemia were quantitated using an image analyzer.
      There was an increase in the transcription of APO-E and GFAP mRNAs, with the
      levels of APO-E mRNA being the highest (3-fold increase on day 7 post-ischemia)
      (P < 0.005). However, we did not see an increase in APP mRNA. In a parallel study
      [Hall, E.D. et al., Exp. Neurol., 135(1995) 17-27], we have also seen an increase
      in levels of APO-E and GFAP protein measured by immunocytochemistry. However, in
      contrast to the lack of an increase in APP mRNA, immunocytochemical measurement
      of APP did show an increase, perhaps due to delayed translation of previously
      formed mRNA. We suggest that neuronal injury or insult results in the induction
      of certain genes (and, therefore, protein synthesis) in the surrounding reactive
      astrocytes, and these proteins may contribute to post-injury amyloidogenesis.

PMID- 8737666
TI  - Discrete brain areas express the insulin-responsive glucose transporter GLUT4.
AB  - Whether or not glucose utilization in the brain is insulin-dependent is still a
      controversial issue. We looked for the presence of the insulin-sensitive glucose
      transporter (GLUT4) in rat brain and obtained the following results: (1) poly(A)
      RNAs from the hypothalamus and anterior medulla oblongata hybridize with a cDNA
      probe for GLUT4; (2) reverse transcription-polymerase chain reaction (RT-PCR) on
      RNA from various brain nuclei detects GLUT4 transcripts; (3) immunocytochemistry,
      using a polyclonal antibody to GLUT4; reveals a specific immunostaining pattern,
      whereas both electronic microscopy and double immunofluorescence staining, using
      a neurofilament protein marker, indicate a neuronal localization. These results
      are discussed in terms of a putative neuromodulator role of insulin, via glucose
      utilization, in brain areas involved in the regulation of fuel metabolism.

PMID- 8737667
TI  - Effect of serotonin on cytokine mRNA expression in rat hippocampal astrocytes.
AB  - Serotonin is a widely distributed neurotransmitter which elicits a range of
      central activities. We examined the effect of serotonin on cytokine mRNA
      expression by rat hippocampal astrocytes in primary cultures. Semi-quantitative
      reverse transcription-polymerase chain reaction (RT-PCR) analysis shows that
      interleukin-6 (IL6) mRNA is expressed after 10(-12) M serotonin stimulation
      whereas transforming growth factor-beta (TGF beta) and tumor necrosis factor (TNF
      alpha) are induced by 10(-10) M serotonin. These inductions appeared after 1 h
      stimulation for IL6 and TNF alpha, whereas that of TGF beta appeared after 4 h.
      The present results provide the first evidence that serotonin can influence
      astrocyte cytokine production, and thus this neurotransmitter may be considered a
      potential neuroimmunomodulator.

PMID- 8737668
TI  - Presence and localization of neurotrophin receptor tyrosine kinase (TrkA, TrkB,
      TrkC) mRNAs in visceral afferent neurons of the nodose and petrosal ganglia.
AB  - The presence of mRNAs to the high affinity tyrosine kinase (Trk) receptors for
      neurotrophins was studied in visceral afferent neurons of the nodose and petrosal
      ganglia of adult and neonatal rats using in situ hybridization histochemistry.
      Neurons containing TrkA mRNA were found in the adult nodose and petrosal ganglia.
      About 10% of nodose ganglion neurons and 38% of petrosal ganglion neurons
      contained TrkA mRNA. The nodose and petrosal ganglia from 1 day old neonates also
      expressed TrkA mRNA. No TrkB mRNA-containing neurons were detected in the adult
      nodose and petrosal ganglia, whereas TrkB mRNA was detected in 1 day old neonatal
      nodose and petrosal ganglia. TrkC mRNA was found in about 9% of nodose ganglion
      neurons and 11% of petrosal ganglion neurons of adult rats. Likewise, low but
      detectable levels of TrkC mRNA were seen in 1 day old neonatal nodose and
      petrosal ganglia. These data demonstrate the presence of TrkA and TrkC in the
      adult nodose and petrosal ganglia and provide a substrate for the ongoing
      neurotrophin-induced regulation of these placodally derived visceral afferent
      neurons. The altered expression of Trk receptor mRNAs in the nodose and petrosal
      ganglia between the adult and neonatal rats may reflect developmentally regulated
      changes in neurotrophin responsiveness.

PMID- 8737669
TI  - Regulation of kappa opioid receptor mRNA in the rat brain by "binge' pattern
      cocaine administration and correlation with preprodynorphin mRNA.
AB  - We previously reported that 'binge' pattern administration of cocaine elevates
      preprodynorphin (ppDyn) mRNA in the caudate-putamen of rats. The present study
      confirms this finding. In addition, we report here that "binge' pattern
      administration of cocaine leads to a significant decrease in the mean level of
      kappa opioid receptor (KOR) mRNA in the substantia nigra, with no significant
      change in the mean level of KOR mRNA in the caudate-putamen. The decrease in KOR
      mRNA in the substantia nigra after 3 day or 14 day 'binge' administration of
      cocaine was comparable to the increase in ppDyn mRNA in the caudate-putamen.
      While there was no significant change in the mean levels of KOR mRNA in the
      caudate-putamen following cocaine administration, there was a positive within
      animal correlation between the levels of ppDyn mRNA and KOR mRNA in the caudate
      putamen, both in animals administered saline and in animals receiving 'binge'
      cocaine for 14 days. Finally, mean levels of ppDyn or KOR mRNA in cocaine treated
      rats were not different from saline treated controls following a 10 day
      withdrawal from 14 days of 'binge' cocaine administration. The results provide
      evidence of regulation of KOR mRNA by cocaine in the substantia nigra.

PMID- 8737670
TI  - Pontine cholinergic neurons show Fos-like immunoreactivity associated with
      cholinergically induced REM sleep.
AB  - Recently, we showed c-fos expression in pontine nuclei in association with
      cholinergically induced REM sleep (REMc). Pontine cholinergic mechanisms have
      been implicated in the orchestration of the phasic and tonic events underlying
      REM sleep. Therefore, in the present study, we examined whether pontine
      cholinergic neurons demonstrate Fos-like immunoreactivity (Fos-LI) following
      cholinergically induced, sustained rapid-eye movement (REMc) sleep in cats.
      Microinjections (0.25 microliter) of vehicle (n = 2) or carbachol (n = 3; 2.0
      micrograms/0.25 microliter) were made into the medial pontine reticular
      formation. Carbachol produced a state with all the signs of natural REM sleep,
      and with durations ranging from 27 to 40.1 min. Animals were killed immediately
      after the end of REMc. Compared to vehicle treated animals (0.9% saline), the
      animals with REMc showed a significantly higher number of Fos-LI cells in pontine
      regions implicated in REM sleep generation. More importantly, 11.2% (SEM +/-
      0.83) of cholinergic neurons in the lateral dorsal tegmental (LDT) and
      pedunculopontine tegmental (PPT) nuclei were determined to be also Fos-LI
      positive. In the vehicle treated animals very few Fos-LI cells were found and
      none of these were found to be cholinergic. These findings indicate that during
      REMc a transcriptional cascade involving c-fos occurs in a subpopulation of
      pontine cholinergic neurons.

PMID- 8737671
TI  - Expression of c-fos mRNA after audiogenic seizure in adult rats with neonatal
      hypothyroidism.
AB  - In situ hybridization histochemistry was used to evaluate the expression of the
      immediate-early gene c-fos following the induction of audiogenic seizures in
      adult rats with transient neonatal hypothyroidism. The rats treated with 0.02%
      propylthiouracil (PTU) through mother's milk during days 0-19 after delivery
      showed a high incidence of seizures to auditory stimulation at the age of 4
      months. The significant induction of c-fos mRNA by audiogenic seizures is
      prominent in several brain areas including central gray, peripeduncular nucleus,
      inferior colliculus, septal nucleus, bed nucleus of stria terminalis, and
      dorsomedial hypothalamus. However, the expression of c-fos mRNA was comparable in
      neocortex, dorsal hippocampus and medial geniculate body between control rats and
      PTU-treated, seizure-induced rats. These results confirm the previous report on
      the c-fos expression following audiogenic seizure sensitized during development
      by a loud noise [20]. The present results indicate that the neonatal PTU
      treatment may provide a useful tool for studying the mechanism underlying the
      seizure susceptibility and development after maturation.

PMID- 8737672
TI  - Selective c-Jun overexpression is associated with ionizing radiation-induced
      apoptosis in the developing cerebellum of the rat.
AB  - Immunohistochemistry to Bcl-2, Bax, c-Myc, c-Fos, Fos-related, c-Jun, Jun B and
      Jun D was used to study the involvement of these factors in ionizing radiation
      induced apoptosis in the cerebellum of the developing rat. Selective c-Jun
      overexpression was observed during the whole process of radiation-induced cell
      death. Furthermore, c-Jun overexpression was restricted to apoptotic cells, as
      shown by double labeling with the method of in situ labeling of nuclear DNA
      fragmentation and c-Jun immunohistochemistry. This is the first in vivo evidence
      that selective c-Jun overexpression is associated with apoptotic cell death in
      the developing nervous system following ionizing radiation.

PMID- 8737673
TI  - Changes in the phosphorylation of eukaryotic initiation factor 2 alpha,
      initiation factor 2B activity and translational rates in primary neuronal
      cultures under different physiological growing conditions.
AB  - Phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 (eIF-2) is
      one of the best known mechanisms regulating protein synthesis in a wide range of
      eukaryotic cells, from yeast to human. To determine whether this mechanism
      operates in primary neuronal cells, we have cultured primary neuronal cells for 7
      days under two optimal growing conditions, complete medium (containing 15% serum)
      and serum-free medium, and determined the protein synthesis rate, eukaryotic
      initiation 2 and 2B (eIF-2B) activities, as well as the level of phosphorylation
      of eIF-2. Cells cultured in serum-free medium exhibited a lower rate of protein
      synthesis (75%), concomitant to a decreased eIF-2 activity (71%), and slightly
      higher eIF-2(alpha P) levels (from 10 to 16% of total eIF-2) with respect to
      cells cultured in complete media. eIF-2B activity, as measured at saturating eIF
      2. GDP concentrations (assay independent on the presence of eIF-2(alpha P)) was
      similar under the two culture conditions. When neurons cultured in serum-free
      medium are exposed to complete medium for only 24 h, there is a clear decrease in
      the phosphorylation of eIF-2 alpha (16-3%). This decrease correlates in time with
      an increase in the protein synthesis rate (154%), as well as eIF-2 activity
      (236%). The increased levels of eIF-2(alpha P), a competitive inhibitor of eIF-2B
      in the guanine-exchange reaction, are responsible for the decreased eIF-2B
      activity found in the neurons cultured in serum-free medium. Additionally, eIF
      2(alpha P) is accountable for the lower effect of exogenous eIF-2B in ternary
      complex formation from preformed eIF-2. GDP in the serum-free media. These
      changes in phosphorylation of eIF-2 alpha in normal mammalian cells in response
      to changes in the extracellular medium are reported here for the first time.

PMID- 8737674
TI  - A new Cys2/His2 zinc finger gene, rKr1, expressed in oligodendrocytes and
      neurons.
AB  - The myelination of nerve fibers is essential for the function of the vertebrate
      nervous system as a prerequisite for fast saltatory conduction of action
      potentials. In the central nervous system (CNS), myelin is produced by
      oligodendrocytes. In order to identify gene regulatory proteins involved in the
      differentiation of this glial cell type or in the expression of myelin-specific
      genes, we have constructed a cDNA library from a highly enriched population of
      rat oligodendrocytes and screened this library for members of the Kruppel family
      of Cys2/His2 zinc finger proteins. One of the identified clones, named rKr1,
      encodes a novel protein of 650 amino acids which contains 12 carboxy-terminal
      zinc finger domains and an amino-terminal acidic domain. On Northern blots, a
      single rKr1 mRNA of 4.3 kb is detected. This message is present in all adult rat
      tissues tested, with the highest levels found in the CNS and testis. In situ
      hybridization on the P15 brain revealed that the transcript is expressed in
      differentiated oligodendrocytes and in subtypes of neurons. Particularly high
      message levels are found in motor neurons of the brainstem and the spinal cord.
      The modular structure of the rKr1 protein, in which a potential DNA binding
      region (the zinc fingers) is combined with a putative activation domain (the
      acidic region), suggests a function as sequence-specific transcriptional
      activator.

PMID- 8737675
TI  - Spermidine/spermine N1-acetyltransferase mRNA levels show marked and region
      specific changes in the early phase after transient forebrain ischemia.
AB  - Considerable evidence points to an involvement of natural polyamines (putrescine,
      spermidine and spermine) in trophic regulation of brain tissue.
      Spermidine/spermine N1-acetyltransferase is the key enzyme in the interconversion
      pathway which leads to the formation of spermidine and putrescine from spermine
      and spermidine, respectively. In the present paper we have studied using in situ
      hybridization histochemistry the levels of spermidine/spermine N1
      acetyltransferase mRNA in the rat central nervous system after transient
      forebrain ischemia. In the first hours after the insult, a modest increase in
      spermidine/spermine N1-acetyltransferase mRNA levels was observed in ependymal
      cells and other non-neuronal cells of all telencephalic and diencephalic regions.
      In addition, major increases in spermidine/spermine N1-acetyltransferase mRNA
      levels were observed in regions selectively vulnerable to the ischemic insult,
      such as striatum, hippocampus and cerebral cortex, during the first day post
      reperfusion. The time course and extent of labelling increase were subregion- and
      cell-specific. At the cellular level, the labelling appeared markedly increased
      in neurons (8-10 fold in ventromedial striatum and CA1 region) and, to a lesser
      extent, in non-neuronal cells. The increase in SSAT mRNA levels was not directly
      related to cell degeneration, as it was detected in both some vulnerable and some
      resistant cell populations. However, the peak increase of SSAT labelling was
      precocious in resistant neurons (such as those of ventromedial striatum and
      dentate gyrus granular layer) and delayed or very limited in vulnerable neurons
      (such as those of CA1 pyramidal layer and dorsolateral striatum). The increase in
      spermidine/spermine N1-acetyltransferase may contribute to the increase in
      putrescine and decrease in spermidine levels observed after ischemia and gives
      further support to the notion that polyamine metabolism in the early phase after
      lesion is oriented towards putrescine production. This phenomenon could be
      relevant in determining the prevalence of neurotrophic vs. neurotoxic effects of
      polyamines.

PMID- 8737676
TI  - Translation initiation sites and relative activity of large and small forms of
      human choline acetyltransferase.
AB  - We have previously shown that translation of human choline acetyltransferase
      (ChAT) mRNA starts at least at two sites and produces two enzyme proteins with
      different molecular weights. In this study, translation initiation sites and
      relative activity of large and small forms of ChAT were determined by site
      directed mutagenesis, followed by expression and immunoblotting analyses. The
      large and small forms were translated at the first and second ATG codons of ChAT
      cDNA, respectively, and the specific activity was almost the same between the two
      forms of the enzyme.

PMID- 8737677
TI  - Regional brain-derived neurotrophic factor mRNA and protein levels following
      transient forebrain ischemia in the rat.
AB  - Levels of BDNF mRNA and protein were measured in the rat brain using in situ
      hybridization and a two-site enzyme immunoassay. Under basal conditions, the
      highest BDNF concentration was found in the dentate gyrus (88 ng/g), while the
      levels in CA3 (50 ng/g), CA1 (18 ng/g) and parietal cortex (8 ng/g) were markedly
      lower. Following 10 min of forebrain ischemia, BDNF protein increased transiently
      in the dentate gyrus (to 124% of control at 6 h after the insult) and CA3 region
      (to 131% of control, at 1 week after the insult). In CA1 and parietal cortex,
      BDNF protein decreased to 73-75% of control at 24 h. In contrast, BDNF mRNA
      expression in dentate granule cells and CA3 pyramidal layer was transiently
      elevated to 287 and 293% of control, respectively, at 2 h, whereas no change was
      detected in CA1 or neocortex. The regional BDNF protein levels shown here
      correlate at least partly with regional differences in cellular resistance to
      ischemic damage, which is consistent with the hypothesis of a neuroprotective
      role of BDNF.

PMID- 8737678
TI  - GAP-43 mRNA expression in early development of human nervous system.
AB  - The temporal and spatial distribution of GAP-43 mRNA in early human development,
      from 6 to 23 gestational weeks (g.w.), was examined by in situ hybridization
      histochemistry. GAP-43 mRNA was expressed as early as 6 g.w. in all regions of
      developing nervous system, the spinal cord, brainstem, cerebellum, diencephalic
      and telencephalic regions. Although the pronounced level of expression persisted
      during the entire examined period, the intensity of expression varied along the
      spatial axis over time. Analysis at the cellular level revealed that early on in
      development (6 g.w.) GAP-43 mRNA was expressed in the entire neuroblast
      population. With the onset of differentiation, at 13-23 g.w., GAP-43 mRNA
      expression had switched to the neurons that are in the process outgrowth. The
      highest level of GAP-43 mRNA expression was localized in the regions consisting
      of differentiating neurons, such as the cortical plate and intermediate zone of
      the telencephalic wall, and several delineated subcortical and thalamic nuclei.
      The spatial and temporal pattern of GAP-43 mRNA expression obtained suggests a
      possible dual role of GAP-43 in the development of the human nervous system: in
      the embryonic brain it could be involved in fundamental processes underlying cell
      proliferation; in the fetal brain its expression is specifically correlated with
      differentiation and the outgrowth of axons.

PMID- 8737679
TI  - Hippocampal glucocorticoid receptor mRNA is up-regulated by acute and down
      regulated by chronic amphetamine treatment.
AB  - Repeated administration of amphetamine-like stimulants to rats results in
      enhanced behavioral responsiveness to subsequent administration of these drugs.
      Recent evidence suggests corticosterone may play a role in the development of
      sensitization perhaps through the down-regulation of glucocorticoid receptor
      (GR). To test this hypothesis further we examined the effects of five daily
      injections of amphetamine (AMPH) (2.5 mg/kg) on GR mRNA of adult Sprague-Dawley
      rats. Two other groups received saline for 4 days and then either saline or AMPH
      on the fifth day. All animals were killed 24 h after the last treatment and in
      situ hybridization was performed with an antisense mRNA GR probe. Quantification
      of hippocampal GR was accomplished by computer analysis of digitized images of
      CA1 and dentate gyrus. Acute AMPH produced a significant up-regulation of GR mRNA
      in CA1 and a nonsignificant trend towards up-regulation in the dentate gyrus.
      Repeated exposure to AMPH resulted in a significant down-regulation in CA1, and a
      nonsignificant trend towards down-regulation in dentate gyrus. These data support
      a role for hippocampal GR mRNA in the development of behavioral sensitization.

PMID- 8737680
TI  - Nuclear localization of functional FGF receptor 1 in human astrocytes suggests a
      novel mechanism for growth factor action.
AB  - Fractionation of human astrocytes revealed the presence of 103, 118, and 145 kDa
      forms of FGF receptor 1 (FGFR1) in isolated nuclei. Only trace amounts of FGFR1
      proteins were detected in the cell membrane or cytoplasmic fractions. Nuclear
      FGFR1 is found in the nucleoplasm and nuclear matrix but not in chromatin. Immuno
      confocal microscopy further demonstrates the intranuclear presence of FGFR1 and
      its colocalization with FGF-2. Nuclear FGFR1 binds to FGF-2 and has tyrosine
      kinase activity. Translocation of functional growth factor receptors into the
      cell nucleus offers a novel mechanism for growth factor action.

PMID- 8737682
TI  - Gonadal regulation of somatostatin receptor 1, 2 and 3 mRNA levels in the rat
      anterior pituitary.
AB  - In order to investigate the gonadal regulation of pituitary somatostatin
      receptors (SSTRs)-gene expression, we studied the existence of sexual dimorphism
      on SSTR1, SSTR2, and SSTR3 mRNA levels in the rat anterior pituitary. The roles
      of testosterone and other non-androgenic testicular factors were also evaluated.
      SSTR1, SSTR2 and SSTR3 mRNA content were assessed by in-situ hybridization in
      male rats lacking the influence of androgenic and/or non-androgenic testicular
      factors. We found that SSTR1 and SSTR3 mRNA levels in the anterior pituitary
      exhibited sexual dimorphism. Moreover, our data indicate that SSTR1 mRNA levels
      are regulated by testosterone, while SSTR3 mRNA content is regulated by non
      androgenic testicular factors. In contrast, SSTR2 levels are not influenced by
      gonadal function.

PMID- 8737681
TI  - Corticotropin-releasing factor up-regulates its own receptor mRNA in the
      paraventricular nucleus of the hypothalamus.
AB  - We investigated the role of CRF in regulating receptor expression in the
      paraventricular nucleus (PVN). First, to clarify the effect of exogenously
      administered CRF, 1 microgram of ovine CRF was injected into rat lateral
      ventricle and changes in concentration of the CRF type 1 receptor (CRF1-R) and
      CRF mRNA in the PVN were semiquantified after in situ hybridization. Second, we
      determined the effect of stress, as a stimulant of endogenous CRF secretion, on
      mRNA accumulation. While CRF1-R mRNA expression was low to be undetectable in the
      PVN of controls, both intracerebroventricular administration of CRF and restraint
      significantly increased CRF1-R and CRF signals in the parvocellular PVN. Thus CRF
      may modulate CRF production and release from the PVN, by regulating CRF1-R
      expression.

PMID- 8737683
TI  - Modulation of adenylyl cyclase by Aplysia bag cell peptides: evidence for a
      common receptor.

PMID- 8737684
TI  - Upper and lower extremity somatosensory evoked potential recording during surgery
      for aneurysms of the descending thoracic aorta.
AB  - Since tibial nerve somatosensory evoked potentials (SEPs) recording is influenced
      by hemodynamic changes and anesthetics, alterations cannot always be attributed
      to spinal cord ischemia, so causing false positive results. Additional recording
      of median nerve SEPs facilitates interpretation. From January 1988 to July 1993,
      60 consecutive patients (44 men, 16 women, mean age 66 years, ranging from 26 to
      83 years) underwent surgery for an aneurysm of the descending thoracic aorta
      using a non-heparinized left heart bypass (Biomedicus pump). In 40 patients
      recording of the tibial and median nerve SEPs was performed intraoperatively by
      stimulating both nerves alternately. In 32 patients (80%) both recordings were
      uneventful. In three patients (7.5%) the tibial nerve SEP temporarily disappeared
      due to peripheral ischemia on termination of the bypass for the creation of an
      open distal anastomosis. In three patients (7.5%) near loss of both tibial and
      median SEP recordings was caused by low blood pressure and/or anesthetics. In two
      patients (5%) isolated loss of the tibial nerve SEP was due to ischemia in the
      spinal pathway of the tibial nerve. The tibial nerve SEP signal returned to
      normal: in one patient after reperfusion of intercostal arteries localized within
      the aneurysm, in the other patient after drainage of cerebrospinal fluid (CSF).
      Continuous recording of both tibial and median nerve SEPs gives consistent
      information on spinal cord ischemia, reducing the false positive rate of the
      lower extremity SEP to 7.5%.

PMID- 8737685
TI  - Open chest and delayed sternal closure after cardiac surgery.
AB  - OBJECTIVES: Open chest (OC) and subsequent delayed sternal closure (DSC) has been
      described as a useful method in the treatment of the severely impaired heart
      after cardiac surgery. METHODS: Prolonged open chest was used in 142 to 3373
      adult cardiac operations (4.2%) between January 1987 and December 1993. The
      indications were: hemodynamic compromise (121), intractable bleeding (9) and
      arrhythmias (12). Delayed sternal closure was carried out in 123 of 142 patients
      at a mean of 2.0 +/- 1.4 days (range 0.5-8 days). Open chest and DSC were used
      proportionally more frequently after combined cardiac surgery (28/293, 9.6%) than
      after coronary artery bypass grafting (CABG) alone (108/2891, 3.7%) or valve
      operation (6/230, 2.6%). RESULTS: Ninety-seven of the 123 who had DSC (78.9%)
      survived and were discharged an average of 8.6 +/- 4.2 days after closure. Fourty
      five patients died: 19 before DSC and 26 after this method. Mortality was related
      to indications for OC: when the indication was low cardiac output the mortality
      was 38.6%, for hemodynamic collapse on closure 0%, diffuse bleeding 33.3% and
      arrhythmias 27.3%. Delayed sternal closure in patients without intraaortic
      balloon pump support was more likely to be successful (mortality rate 4/25, 16.0%
      versus 35/76, 46.3%, P < 0.01). Superficial sternal wound infection occurred in 2
      of 123 (1.6%) patients after DSC, mediastinitis in 1 (0.8%) and sternal
      dehiscence in 3 (2.4%) patients, which does not differ from a control population
      that had primary sternal closure. The follow-up of 97 survivors at an average of
      28 +/- 4 months revealed an improvement of NYHA class by 1.4 +/- 0.4. There were
      16 deaths (13 cardia-related) during the follow-up period and 3 redo CABG. One
      case of sternal osteomyelitis occurred without any other late sternal morbidity.
      CONCLUSIONS: This study shows that OC with DSC is a beneficial adjunct in the
      treatment of postoperatively impaired cardiac function, profuse hemorrhage and
      persistent arrhythmias. It can be performed without increased sternal morbidity.
      Long-term results are also encouraging.

PMID- 8737686
TI  - Value of body plethysmography in preoperative assessment of thoracotomy
      candidates.
AB  - The usefulness of body plethysmography in the assessment of thoracotomy
      candidates is not well documented. Reported thresholds for operability are
      generally expressed in absolute values, which do not take into account a
      patient's size, age or gender. Spirometric and plethysmographic data of 103
      patients undergoing thoracotomy were examined for their ability to predict death
      due to cardiopulmonary insufficiency, pneumonia, and atelectasis during the first
      30 postoperative days. Neither plethysmographic nor spirometric parameters could
      predict atelectasis. Patients who underwent lobectomy were susceptible to the
      development of atelectasis. A weak correlation between elevated functional
      residual capacity (FRC) and occurrence of postoperative pneumonia was found. Lung
      function testing was not able to separate survivors from non-survivors. Patients
      with pneumonia were at high risk of death in their postoperative course. Because
      of the non-linear relationship, a correlation coefficient between spirometric and
      plethysmographic variables was not calculated. The prevalence of cardiac risk
      factors was high, so the decision for invasive hemodynamic studies should rather
      be based upon a patient's history than restricted to patients with impaired lung
      function. Because of methodological differences, and probably insuitable
      reference values, body plethysmography cannot substitute for spirometry. For FRC
      and FRC to total lung capacity (FRC/ TLC) ratio, further investigations must be
      undertaken to establish a correct reference value.

PMID- 8737687
TI  - Tricuspid valve reconstruction, a treatment option in acute endocarditis.
AB  - Tricuspid valve endocardititis is treated surgically by total valve excision or
      valve replacement. Both procedures are controversial with regard to the
      hemodynamic consequences and to the long-term prognosis. In the following,
      results of tricuspid valve repair in acute infective endocarditis are reported
      and discussed as an additional treatment option. Between January 1988 and
      December 1993, 118 patients were operated on for acute valve endocarditis at our
      institution. Eleven of these patients had tricuspid valve endocarditis, isolated
      (n = 7) or combined with endocarditis of a left-sided valve (n = 4). In the cases
      with isolated tricuspid valve endocarditis, the indication for surgery was
      intractable infection in six and hemodynamically relevant tricuspid insufficiency
      in one out of seven patients. In all patients with associated left-sided
      endocarditis, the indication was hemodynamic deterioration. In eight patients the
      tricuspid valve endocarditis was treated as follows: debridement, vegectomy,
      patch reconstruction of the cusps, reducing the cusps to two. In three patients
      reconstruction was not possible because of extensive involvement of all parts of
      the valve, including the valve ring and the papillary muscles. In these patients
      primary valve replacement (n = 1) or valve excision with secondary replacement (n
      = 2) was performed. In four patients tricuspid reconstruction was combined with
      mitral (n = 1), aortic (n = 1) or double valve replacement (n = 2).
      Postoperatively, signs of infection vanished in all surviving patients (n = 10)
      and tricuspid valve endocarditis healed without recurrences. Implanted prosthetic
      material did not lead to recurrent infection. One patient died early
      postoperatively after valve excision, in septic shock and multi-organ failure. In
      seven patients late echocardiographic follow-up showed tricuspid regurgitation
      grade 0 in three patients, I in two, II in one and III in one. Our results
      suggest that valve repair is a reasonable treatment option for tricuspid valve
      endocarditis in all cases with localized infection of the valve. Only if
      extensive valve destruction excludes valve repair, would we now favor primary
      valve replacement over simple valvulectomy. In all other cases primary valve
      reconstruction is the treatment of choice for tricuspid valve endocarditis, if
      surgery is indicated.

PMID- 8737688
TI  - Cephalic veins in coronary artery bypass surgery.
AB  - Various alternative conduits for aortocoronary bypass grafting have been
      suggested when the saphenous vein quality is inadequate. During a 10-year period
      we have used the cephalic vein in 39 patients. Eighteen entered an angiographic
      follow-up study. A total of 31 arm vein grafts were used with 43 distal
      anastomoses. When calculating patency by number of patent distal anastomoses,
      this was 46% (median follow-up was 31 months), but calculating by the number of
      patent grafts we found 52% patency (median follow-up 31 months). In conclusion,
      we discourage others from using arm veins in aortocoronary bypass operations.

PMID- 8737689
TI  - Results of unifocalization for pulmonary atresia, ventricular septal defect and
      major aortopulmonary collateral arteries: patency of pulmonary vascular segments.
AB  - Unifocalization, a surgical technique to unifocalize the pulmonary blood supply
      in patients with pulmonary atresia, ventricular septal defect and major
      aortopulmonary collateral arteries, is a useful preparative operation to extend
      the indication for corrective surgery. The preoperative and postoperative
      pulmonary angiograms of 51 patients (aged 3 months-26 years at first
      unifocalization, 29 males, 22 females), who underwent a total of 96
      unifocalizations from December 1985 to July 1994, were studied to assess the
      effectiveness of each procedure of unifocalization. The procedures of
      unifocalization were ligation (9), angioplasty (6), direct anastomosis (25),
      bridging (6), additional central pulmonary artery creation (9), central pulmonary
      artery creation (36) and thrombectomy (5). Altogether 125 anastomoses were made,
      and the patency of 101 (80.2%) anastomoses was confirmed, 24 (19.2%) were shown
      to be occluded. The patency rate of the anastomoses between xenograft rolls and
      intrapulmonary arteries was 79.5% (70/88), while that between native central
      pulmonary arteries and intrapulmonary arteries was 83.8% (31/37; N. S.). The
      patency rate of the anastomoses involving intrahilar arteries was 88.0% (44/50),
      while that for the group involving extrahilar arteries only was 71.9% (46/64; P <
      0.05). It is concluded that 1) unifocalization with the reconstruction of central
      pulmonary arteries using a pericardial roll is a useful method for patients with
      absent or hypoplastic central pulmonary arteries, 2) it is preferable to divide
      the fissures of lung in anastomosing pulmonary arteries of arborization
      abnormalities.

PMID- 8737690
TI  - The effect of pentoxifylline on the lung during cardiopulmonary bypass.
AB  - Cardiopulmonary bypass (CPB) produces an inflammatory response due to the
      interaction of blood with a foreign body surface. The lungs are most affected by
      this inflammatory response. Pentoxifylline (PTX), a phosphodiesterase inhibitor
      and an inhibitor of leukocyte activation, is used to minimize damage in lungs
      where leukocytes play an important role. Twenty patients with mitral valve
      stenosis with planned mitral valve surgery were included in the study. The ten
      patients receiving pentoxifylline (PTX group) were administered 400 mg PTX orally
      TID for 3 days preoperatively and, following anesthetic induction, a 300 mg PTX
      infusion was given. The ten patients receiving no PTX were the control group
      (CT). Platelet and leukocyte counts, mean pulmonary arterial pressure (mPAP),
      pulmonary capillary wedge pressure (PCWP), cardiac index (CI), pulmonary vascular
      resistance (PVR), alveolar-arterial PO2 gradient (AaDO2) were measured just
      before and after CPB, and 2 h postoperatively. The number of the leukocytes
      increased in the blood samples drawn 15 min after CPB in both groups and 2 h
      postoperatively showed no statistical change. The number of platelets had
      decreased significantly at the end of the CPB in both groups and, 2 h
      postoperatively, there was a further decrease in the blood count in the control
      group (P < 0.05). There was no significant difference in either the preoperative
      or postoperative PAP, PAWP, and CI. Pulmonary vascular resistance increased in
      both groups following the CPB (CT, before: 136 +/- 44, after: 177 +/- 94 dyne.
      sec.cm-5; PTX, before: 151 +/- 82, after 182 +/- 43 dynes.sec.cm-5). Two hours
      postoperatively, a considerable increase continued in the control group (CT 219
      +/- 170 dynes.sec. cm-5), while there was an insignificant increase in the PTX
      group (PTX 193 +/- 51 dynes.sec.cm-5) (P < 0.05). The alveolar-arterial PO2
      gradient increased after the CPB in both groups but a moderate decrease was
      observed 2 h postoperatively. In lung biopsy specimens taken before and after the
      CPB, there was marked leukocyte sequestration in the control group, whereas the
      number of leukocytes was seen to be insignificant in the PTX group (P < 0.005).
      This dosage regimen of PTX inhibits the postoperative increase in PVR and greatly
      minimized leukocyte sequestration in the lung due to CPB.

PMID- 8737691
TI  - Surgical resection of pulmonary metastases from colorectal carcinoma. Five-year
      survival and main prognostic factors.
AB  - Between 1986 and 1994, 19 patients underwent pulmonary resection for metastatic
      colorectal carcinoma. The mean interval between colon resection and appearance of
      pulmonary metastasis was 41 +/- 21 months. All the patients had no more than two
      metastases. Wedge resection alone or associated with lobectomy was performed in
      four patients, lobectomy in ten, and pneumonectomy in five. One patient died
      within the month after surgery. Mean follow-up was 35 +/- 26 months. The 5-year
      survival rate was 38.7%. Repeat thoracotomy for recurrent metastases was
      performed in one patient. The disease-free interval, the size of metastases, the
      type of pulmonary resection, and the location and the stage of primary cancer had
      no apparent influence on survival, but the survival rate at 4 years was 25% for
      patients with high carcinoembryonic antigen (CEA) level versus 80% for those with
      low CEA level. We conclude that, at least when the number of metastases is less
      than two, resection of colorectal lung metastasis is safe and effective.

PMID- 8737692
TI  - Respiratory muscle strength after lung resection with special reference to age
      and procedures of thoracotomy.
AB  - Changes in respiratory muscle strength after lung resection were examined
      concerning age and procedures of thoracotomy. Maximum inspiratory (MIP) and
      expiratory (MEP) mouth pressure were measured before operation and 1, 2, 4, and
      12 weeks after operation in 81 patients undergoing lung resection. In 48 patients
      undergoing pneumonectomy, lobectomy, or segmentectomy, patients older than 70
      showed a significantly lower MIP and MEP before operation and throughout the
      postoperative period compared to younger ones (P < 0.01). Furthermore, the older
      patients showed a significantly lower percentage of postoperative MIP and MEP 4
      weeks after operation than the younger ones (P < 0.01). In 31 patients undergoing
      lung wedge resection, patients undergoing limited thoracotomy (LT) and video
      assisted thoracic surgery (VATS) showed significantly higher percentages of
      postoperative MIP and MEP than those undergoing posterolateral thoracotomy (PLT)
      1 and 2 weeks after operation (P < 0.01 or 0.05). But there was no significant
      difference in the values between LT and VATS. We concluded that (1) elderly
      patients suffered respiratory muscle weakness before and after operation and
      their postoperative recovery of respiratory muscle strength was slower than in
      younger patients, and (2) VATS and LT resulted in more rapid recovery of
      respiratory muscle strength than PLT, but the difference between VATS and LT was
      not significant.

PMID- 8737693
TI  - Resectional surgery in carcinoma of the oesophagus and cardia: what influences
      long-term survival?
AB  - OBJECTIVE: Our objectives were to determine factors which influence survival
      after resectional surgery in patients with cancer of the oesophagus and cardia.
      PATIENTS AND METHOD: 562 consecutive patients with primary cancer of the
      oesophagus or gastric cardia (oesophago-gastric junction) undergoing resectional
      surgery and reconstruction of the oesophagus were studied. Operative approach
      depended on tumour location, the aim being complete resection of the tumour and
      associated lymph nodes. Postoperative staging was based on tumour, nodes and
      metastasis (TNM) classification. RESULTS: There were 342 males and 220 females,
      aged 61.8 +/- 12.8 years. Histology of the tumours was: squamous cell carcinoma
      49%, adenocarcinoma 47.5% and other tumours 3.5%. The location of tumours within
      the oesophagus was: cervical (n = 32), upper thoracic (n = 18), middle thoracic
      (n = 241) and lower thoracic and gastric cardia (n = 271). Of the tumours 16%
      were stage I, 10% stage II and 74% stage III. Hospital mortality rate was 9%
      overall, significantly higher in cervical tumours (cervical tumours versus lower
      and or middle oesophageal tumours: P < 0.05), the elderly (age > 75 years versus
      age < 75 years: P < 0.05) and stage III disease (stage III versus stage I: P <
      0.001). The overall 5-year survival rate was 18%. There was no correlation
      between tumour histology, location or type of operation and long-term survival.
      Survival disease-free for 5 years or more was 73% for stage I, 15.8% for stage II
      and 6% for stage III. The only significant correlation was between the stage of
      disease and long-term survival (stage I versus stage III P < 0.001, stage I
      versus stage II P < 0.05). CONCLUSIONS: Immediate results are affected by a
      number of factors but long-term survival is related entirely to the stage of the
      tumour.

PMID- 8737694
TI  - Pharyngo-oesophageal dysphagia: surgery based on clinical and manometric data.
AB  - High or pharyngo-oesophageal dysphagia (PD) is defined as difficulty in
      initiating the act of swallowing within 1s. It involves the mechanisms
      controlling the tongue, pharynx and upper oesophageal sphincter (UOS) and is
      associated with a wide variety of local, neurologic and muscular disorders, and
      can also occur after surgery in the area and in response to gastro-oesophageal
      reflux (GOR). Our study aims at defining the criteria for surgery in PD and to
      evaluate the clinical results of such treatment. Twenty-three patients who
      underwent surgery were evaluated with pharyngo-oesophageal motility and
      ambulatory 24-hr pH-metry. The following parameters were measured: 1) pharyngeal
      contraction amplitude, 2) duration, 3) repetitive pharyngeal contractions, 4) UOS
      tone, 5) percentage of UOS relaxation, 6) duration of relaxation, 7) UOS closing
      pressure, 8) UOS closing duration, 9) co-ordination of UOS closing pressure and
      upper oesophageal (UO) contractions. Preoperative manometry showed a variety of
      abnormalities in several of the parameters, such as prolonged pharyngeal
      contraction ("spasm"), unco-ordinated pharyngeal contractions and UOS relaxation,
      low amplitude pharyngeal contractions, unco-ordinated UOS closing tone and UO
      contractions and hypotonic UO. Surgery was directed at the specific abnormality
      in each patient taking into consideration the presence or absence of GOR.
      Seventeen patients (74%) had excellent results. Three other patients (13%), who
      had improved swallowing but who continued to have GOR complicated by some
      oesophageal dysmotility, oesophagitis and an oesophageal web, underwent
      subsequent anti-reflux surgery with relief of symptoms. In conclusion, pharyngo
      oesophageal motility measurement is mandatory in PD, especially when a
      diverticulum is absent. Cricopharyngeal myotomy with or without diverticulectomy
      as indicated produces excellent results. Associated oesophageal problems have to
      be dealt with appropriately.

PMID- 8737695
TI  - Endothelial cell seeding improves patency of synthetic vascular grafts: manual
      versus automatized method.
AB  - Lack of an endothelial surface is the most important variable causing the
      relatively poor patency of synthetic bypass grafts. This study was designed to
      investigate the effect of endothelial cell seeding on small-diameter Dacron
      grafts seeded with microvascular endothelial cells from omentum, and to evaluate
      two methods (manual vs automatized) for one-stage seeding in a canine carotid
      artery model. In 30 mongrel dogs microvascular endothelial cells were harvested
      from omentum, either by a manual or an automatized method, and seeded onto 6-mm
      internal diameter Dacron prostheses prior to the graft interposition into the
      common carotid arteries. Non-seeded Dacron grafts were used as control grafts.
      All dogs received dipyridamole (75 mg/day) and acetylsalicylic acid (325 mg/day)
      for 4 weeks. The prostheses were explanted between 2 and 26 weeks after
      insertion. The results were assessed by patency, angiography, light and scanning
      electron microscopy, transmission electron microscopy, and morphometry.
      Endothelial cell seeding improved the patency rate significantly, regardless of
      the seeding methods used. The overall actuarial patency rates at 5, 12, and 26
      weeks were 98%, 94% and 94%, respectively, for the seeded Dacron grafts, and 92%,
      62% and 54%, respectively, for the non-seeded grafts. The automatized method
      yielded more endothelial cells per gram of omental tissue than the manual method
      (P = 0.0002), but there was no difference (P = 0.34) between the seeding
      densities per square centimeter of the graft surface. The harvesting and seeding
      by the automatized method took 55 min for the whole procedure, 20 min less than
      the manual method. We concluded that one-stage endothelial cell seeding with
      omental microvascular endothelial cells improved the patency of small-diameter
      Dacron grafts in a canine model. The automatized method obtained excellent
      results comparable to the manual procedure, and also reduced the time necessary
      for the cell seeding.

PMID- 8737696
TI  - An alternative method for repair of aortico-left ventricular tunnel associated
      with severe aortic stenosis presenting in a newborn.
AB  - Although a rare congenital anomaly, aortico-left ventricular tunnel (ALVT)
      presents in infants as severe aortic regurgitation which can be successfully
      corrected at the time of diagnosis. In this neonatal case of ALVT, the dominant
      clinical presentation was of severe aortic stenosis. Ultimately, aortic root
      replacement with an aortic homograft was required to repair both the ALVT and the
      dysplastic, stenotic aortic valve.

PMID- 8737697
TI  - Homograft replacement of thoraco-abdominal aorta for a leaking mycotic aneurysm.
AB  - We report the case of a 67-year-old, diabetic patient who underwent antibiotic
      preserved homograft replacement of a thoraco-abdominal segment of the aorta for
      leaking mycotic aneurysm. This was successful in eradicating the sepsis and no
      graft complication had occurred at (18 months). Follow-up with computed
      tomography (CT) scanning.

PMID- 8737698
TI  - A case report on the use of recombinant hirudin as an anticoagulant for
      cardiopulmonary bypass in open heart surgery.

PMID- 8737699
TI  - Extensive resection with selective cerebral perfusion for a lung cancer invading
      the aortic arch.
AB  - An extensive operation for lung cancer invading the aortic arch is reported. A 66
      year-old man presented the recent onset of hoarseness. Chest computed tomography
      and magnetic resonance imaging demonstrated a tumor of the Botallo lymph node
      invading the aortic arch. Left pneumonectomy with combined resection of the
      aortic arch was performed with the use of brain-isolated cardiopulmonary bypass.
      The aortic arch was resected and replaced by an artificial graft. Pathological
      examination revealed a primary lesion of adenocarcinoma in the left upper lobe
      and contiguous lymph node involvement, pT4N2M0. He was discharged and followed as
      an outpatient, however he died of miswallowing 10 months later. Such an extensive
      operation may be of value in selected patients.

PMID- 8737700
TI  - Uveal melanoma: updated considerations on current management modalities.
AB  - Published data on growth rates of uveal melanomas and effects of treatment
      modalities raise important considerations. Dissemination from uveal melanomas
      starts after the tumour is larger than 7 mm diameter; growth from 7 to 10 mm
      diameter increases the risk of metastases incrementally to approximately 16%.
      Estimations of tumour doubling times indicate that metastatic death before 8
      years is nearly always due to pre-therapeutic dissemination so that the impact on
      survival by therapy can only be assessed thereafter. Histopathology on irradiated
      melanomas reveals that reproductive activity has not been suppressed and the
      anticipated (and unfavourable) risk of metastases is not balanced by poor post
      irradiation visual acuity. Also the psychological well-being of a patient with a
      functional fellow eye is better after primary enucleation. Conservative
      management is most appropriate for: small melanomas, patients with a short life
      expectancy, melanomas in a single functioning eye, and patients refusing
      enucleation.

PMID- 8737701
TI  - Indocyanine green angiography in the juvenile haemorrhagic choroidopathy.
AB  - Juvenile haemorrhagic choroidopathy (JHC) is an idiopathic syndrome marked by
      macular choroidal neovascularization (CNV) in patients under the age of 50. We
      used fluorescein angiography (FA) and indocyanine green angiography (ICGA) to
      examine 17 patients with macular CNV and JHC. CNV was always unilateral. On ICGA
      examination the CNV were weakly fluorescent in 59% of cases, hyperfluorescent in
      the remaining 41%. ICGA showed up the following alterations: a) areas with
      diffuse choroidal hyperfluorescence at the posterior pole or in the peripapillary
      region in 11 affected eyes (65%), in the fellow eye too in 5 patients; b) areas
      of choroidal hypofluorescence at the posterior pole but also outside the vascular
      arcades in 2 affected eyes (12%). In conclusion, ICGA does not appear
      indispensable for detecting CNV in JHC but this method does show up diffuse
      choroidal alterations not detectable with FA. The pathogenetic implications of
      the ICGA findings are discussed.

PMID- 8737702
TI  - Determination of the pseudofacility by fluorophotometry in the human eye.
AB  - PURPOSE: Pseudofacility (decrease in aqueous humor flow in response to increase
      in the intraocular pressure (IOP)) has been evaluated in animals and in humans by
      a combination of different techniques that seriously alter the ocular physiology,
      such as the cannulation of the eyeballs, use of radioactive isotopes, perilimbic
      suction cups or tonography. Very different results have been obtained. Our
      objective is to relate the value of the aqueous humor flow in humans (as measured
      by fluorometry) with IOP. In order to obtain the widest range of IOP possible, we
      have performed this study in both normal as well as glaucoma patients. METHODS:
      48 eyes were studied, corresponding to 31 subjects (mean age 58 +/- 14 years). Of
      these, 21 corresponded to normal subjects and 27 to glaucoma patients. The
      aqueous humor flow (F) was determined by fluorophotometry (Protocol of Yablonsky)
      and the IOP was measured thereafter. RESULTS: The mean value of F was 2.1 +/- 0.5
      microliter/min for healthy eyes and 2.2 +/- 0.7 microliter/min for glaucoma
      affected eyes. The values were not different (p > 0.1). The mean value of the IOP
      was 15.3 +/- 3.1 mmHg in the normal population and 22.1 +/- 4.3 mmHg in the
      glaucoma patients. A linear relationship between F and IOP was found (r = -0.41,
      p < 0.05, decrease in F = 0.081 microliter min-1 mmHg-1). CONCLUSIONS: The value
      of the pseudofacility in the humans can be estimated at 0.081 microliter min-1,
      mmHg-1, which constitutes 27% of the total outflow facility. This figure also
      makes it possible to estimate the role of the ultrafiltration in blood in the
      production of the aqueous humor since it is assumed that active secretion is
      pressure-independent. The results obtained are concordant with a secondary but no
      unimportant role of the plasmatic ultrafiltration with respect to the active
      secretion.

PMID- 8737703
TI  - Corneal metabolism and epithelial barrier function after cataract surgery and
      intraocular lens implantation: a fluorophotometric study.
AB  - PURPOSE: The aim of this study was the assessment of possible changes in corneal
      metabolism and epithelial barrier function after an extracapsular lens extraction
      with artificial lens implantation. METHODS: Ten patients without any eye
      medication were selected out of 140 patients attending for extracapsular lens
      extraction with lens implantation at the university hospital. Corneal metabolism
      was evaluated by fluorophotometric measurement of corneal autofluorescence. The
      corneal fluorescence values were corrected for interference by the fluorescence
      of the ocular lens. Corneal epithelial barrier function was evaluated by
      determination of corneal epithelial permeability. The permeability was calculated
      from the fluorescein penetration into the cornea after application of an eye bath
      containing fluorescein. Operated and fellow eyes were investigated 1 week before
      and 3-4 weeks after the operation. RESULTS: The corneal autofluorescence of the
      operated eye decreased significantly after surgery (mean decrease: 14%, Wilcoxon
      paired-sample test: P = 0.038). The corneal epithelial permeability of both eyes
      increased after surgery above the normal range of healthy controls (mean increase
      operated eye: 34%, P = 0.015, fellow eye: 32%, P = 0.15). Both corneal
      autofluorescence and epithelial permeability returned to normal values after one
      year. CONCLUSIONS: The lower corneal autofluorescence in the operated eye after
      surgery indicates a lower corneal metabolism which may be due to surgery. The
      increased epithelial permeability of both eyes implies a temporary impairment of
      the corneal barrier function. The interaction with the fellow eye indicates a
      consensual reaction which may attributed to damage to the neural system by the
      surgery.

PMID- 8737704
TI  - Effects of subconjunctival methylprednisolone on the blood aqueous barrier
      following cataract surgery.
AB  - The aim of this double-blind randomized study was to assess the effect of
      subconjunctival methylprednisolone hemisuccinate (MH) on the recovery of the
      blood aqueous barrier (BAB) following uncomplicated cataract surgery performed by
      the same surgeon in normal eyes. Fifty eyes of fifty patients (28 female, 22
      male, mean age 72.3 +/- 11.2 years) were randomized into two groups: group 1
      received a subconjunctival injection of MH (40 mg in 0.5 cc) at the end of the
      surgery and group 2 did not. All patients were free of other ocular or systemic
      diseases known to alter the BAB and were not taking any anti-inflammatory
      medications. Postoperative treatments were similar in both groups. The patients
      were submitted to laser flare photometry 30 minutes to one hour after mydriasis
      with a drop of tropicamide preoperatively and on the first, second and seventh
      day and then one month and six months following surgery. No difference in aqueous
      flare was seen between the two groups on any of postoperative visits. These data
      suggest that subconjunctival MH has no beneficial effect in postoperative BAB
      permeability following uncomplicated cataract surgery in normal eyes.

PMID- 8737705
TI  - Diode laser photocoagulation of choroidal hemangioma.
AB  - BACKGROUND: The argon laser photocoagulation has recently become the treatment of
      choice in choroidal hemangioma. We evaluated the efficacy of the near infrared
      wavelength diode laser in the treatment of such tumours. This wavelength is not
      highly absorbed by the retinal pigment epithelium and penetrates deep into the
      choroid. METHODS: Two cases of choroidal haemangioma with a serous detachment of
      the neural retina were diagnosed with ophthalmoscopy, fluorescein and indocyanine
      green angiography, A-scan and B-scan ultrasonography and treated with a surface
      photocoagulation with a diode laser. The efficacy of photocoagulation was
      evaluated three, six, twelve and fifteen months after laser treatment. RESULTS:
      The resorption of the subretinal fluid and a reduction in thickness of the tumour
      followed laser photocoagulation. CONCLUSIONS: Diode lasers might be effective in
      the treatment of choroidal haemangioma.

PMID- 8737706
TI  - Branch retinal artery occlusion (BRAO) combined with branch retinal vein
      occlusion (BRVO) and optic disc neovascularization associated with HIV and CMV
      retinitis.
AB  - Two vaso-occlusive events, branch retinal artery occlusion (BRAO) and branch
      retinal vein occlusion (BRVO), were observed in the retina of an HIV-infected
      patient with cytomegalovirus (CMV) retinitis who developed neovascularization of
      the disc (NVD). Although BRVO and reversible NVD have been reported in
      association with CMV retinitis, we have seen no reports of concomitant BRAO. CMV
      damages endothelial cells and causes an occlusive vasculitis. In HIV-infected
      individuals, damaged endothelial cells and rheologic problems result in increased
      blood viscosity. HIV infection has also been associated systemically with
      elevated levels of cytokines, including tumor necrosis factor alpha (TNF-alpha).
      In vitro, TNF-alpha exerts effects that decrease fibrinolytic potential; this
      activity in the circulation of a patient with AIDS may lead to vascular occlusive
      events. In the patient reported here, the retinal changes were not reversed by
      induction therapy with ganciclovir and the NVD did not regress.

PMID- 8737707
TI  - Asymmetric fundus flavimaculatus/Stargardt's disease, associated with unilateral
      myopia.
AB  - An unusual asymmetric pattern of fundus flavimaculatus was observed in a
      unilateral myopic patient. Although electrophysiologic testing was similar for
      both eyes, fundus lesions were different and less pronounced in the myopic eye.

PMID- 8737708
TI  - Acute and long-term effects of prostaglandin E1 assessed by clinical and
      microcirculatory parameters in critical limb ischemia: a pilot study.
AB  - We treated 14 patients suffering from critical limb ischemia (CLI) as defined by
      the Consensus Document, and in whom possibilities of surgical or percutaneous
      arterial reconstruction were excluded, by PGE1 60 micrograms i.v. daily during 3
      weeks. Effects were evaluated by clinical, macrocirculatory and microcirculatory
      parameters during a follow-up of 1 year. After treatment with PGE1, we noted a
      significant reduction in analgesic use and in pain score. The average tcpO2
      values on the forefoot in the supine and sitting positions, with or without
      inhalation of O2 through a face mask, showed a significant improvement after 3
      weeks, as well as capillary stage. Laser Doppler flux did not change, but was
      significantly higher in diabetic patients than in nondiabetics with CLI. In 4
      patients (28%) no improvement could be found after 3 weeks' treatment. Although
      in 6 patients the improvement lasted for up to 4 months, the legs eventually
      deteriorated. In 4 patients (28%) the legs were preserved after 1 year without
      further active therapy. No patient with initial tcpO2 values above 40 mm Hg in
      the supine and 100 mm Hg in the sitting positions during O2 inhalation lost a
      leg. Although other effects like local care could have influenced the outcome
      favorably, we noticed a beneficial albeit transient effect of PGE1 for the
      majority of our patients with CLI. TcpO2 measurements with O2 inhalation might be
      a valuable predictor of a positive long-term result.

PMID- 8737709
TI  - Analysis of laser Doppler flux motion in man: comparison of autoregressive
      modelling and fast Fourier transformation.
AB  - In order to investigate laser Doppler (LD) flux motion in healthy subjects and
      patients with peripheral arterial occlusive disease (PAOD), spectrum analysis of
      LD signals is needed. Autoregressive analysis (AR) is presented as an alternative
      method of power spectrum estimation. This procedure is compared to the commonly
      used fast Fourier transform algorithm (FFT) by describing the analytical power of
      both spectra in the analysis of flux motion waves. LD signals were recorded from
      the forefoot of 8 healthy volunteers and 11 patients with different degrees of
      PAOD. The flux, concentration of moving blood cells and velocity signal was
      digitized and stored for off-line analysis. Special software was designed to
      calculate AR and FFT spectra of the LD signals and to compare the suitability of
      both methods for the spectral analysis of LD recordings. Additionally, three
      dimensional spectrum diagrams were calculated to demonstrate time-dependent flux
      changes during standardized provocation maneuvers. AR facilitates the
      determination of frequency and amplitude of flux motion waves as compared to the
      FFT. Low frequency-large amplitude waves (LF waves) were detected in both groups.
      High frequency-small amplitude waves (HF waves), which predominantly appear in
      severe ischemia, were observed in 7 of the 11 patients and in 2 of the 8
      controls. The spectra revealed pulsatile waves in all healthy controls, but only
      in 1 of the 11 patients. AR modelling allows a reliable description of important
      flux motion components and has considerable advantages in spectral estimation of
      LD signals as compared to the FFT.

PMID- 8737710
TI  - The influence of adenosine on red blood cell flow cessation in skeletal muscle.
AB  - The observed positive correlation between cessation of red blood cell flow in
      capillaries at low perfusion pressures and the oxygen tension (PO2) in the
      superfusion solution may be due to oxygen-dependent arteriolar constriction. To
      test this hypothesis, we investigated capillary flow cessation during aortic
      occlusion and concomitant changes in diameters of terminal arterioles and
      capillaries in normal and vasodilated vascular beds of rabbit tenuissimus muscle
      (n = 15) by means of video intravital microscopy. In the vasodilated bed,
      arteriolar tone was eliminated by local application of 10(-4) M adenosine (ADO).
      The PO2 in the superfusate was varied locally, i.e., in the solution between
      objective lens and muscle surface. At a local PO2 of 40 mm Hg without ADO, flow
      ceased in about 50% of the capillaries during aortic occlusion while the
      arterioles dilated to 118% of control (median; p < 0.001). Addition of ADO led to
      an increase in arteriolar and capillary diameter to 220% (median; p < 0.001) and
      121% (median; p < 0.05), respectively. Under ADO, the incidence of capillary flow
      cessation was reduced (p < 0.05) to about 20%. Elevation of the local PO2 from 40
      to 100 mm Hg in the presence of ADO did not lead to a significant change in the
      incidence of flow cessation, nor to changes in arteriolar or capillary diameter.
      In the presence of ADO, median arteriolar and capillary diameters during aortic
      occlusion were 96% (p < 0.001) and 7% (p < 0.05) larger than their control
      diameters without ADO, respectively. In summary, it is suggested that the
      incidence of flow cessation may depend on both the arteriolar and the capillary
      diameter. Of these two factors, capillary diameter may be the most important one,
      because its changes affect the interaction between red blood cells and the vessel
      wall in the narrow capillaries, and, hence, the resistance to flow. In the
      presence of ADO, at elevated local PO2 levels flow cessation still occurs in
      about 20-30% of the capillaries, suggesting that arteriolar contraction is only
      in part responsible for the incidence of flow cessation.

PMID- 8737711
TI  - Pyogenic granuloma stimulates angiogenesis in the chick embryo chorioallantoic
      membrane.
AB  - Ten samples of pyogenic granuloma and 10 of normal skin from age- and sex-matched
      controls were grafted onto the chick embryo chorioallantoic membrane (CAM) to
      investigate their possible angiogenic activity. The angiogenic response in
      pathological and control implants was assessed on histologic sections by a
      planimetric point-count method 4 days after grafting. The CAM mast cells were
      also quantified. The vascular counts in the area underlying the pyogenic
      granuloma were four times higher than those of normal skin. A higher number of
      mucosa-like mast cells was detected in the intermediate mesenchyme of the CAM in
      pathological samples in comparison to controls. Pyogenic granuloma may promote
      angiogenesis leading to release of several angiogenic factors. The role played in
      angiogenic response by the inflammatory cells, mainly mast cells, forming the
      perilesional infiltrate was supported by this study.

PMID- 8737712
TI  - Measurement of neutrophil content in brain and lung tissue by a modified
      myeloperoxidase assay.
AB  - Myeloperoxidase (MPO) activity is assessed for the quantification of neutrophil
      accumulation in tissues. In particular, it may be used to support in vivo data on
      leukocyte kinetics obtained by intravital microscopy and to clarify whether
      phenomena observed on the organ surface reflect the situation of the whole organ
      microcirculation. Previous measurements of MPO activity were limited by
      interference with other peroxidases and by inhibition of MPO activity by specific
      enzymes. To circumvent these limitations, a modified assay was devised that
      combined a two-step tissue homogenization technique with heat incubation in a
      continuous photometric measurement. MPO activity was quantified in neutrophils
      isolated from rat and rabbit whole blood, rat brain and rabbit lung and compared
      with intravital microscopic data on leukocyte accumulation. The modified assay is
      characterized by high reproducibility, strong correlation of MPO activity with
      number of neutrophils and full recovery of neutrophils added to tissue
      homogenate. MPO activity per neutrophil was 342.9 +/- 11.7 mU/10(6) cells in rats
      and 40.3 +/- 0.8 mU/10(6) cells in rabbits. MPO activity in tissue was
      significantly lower in rat brains (18.9 +/- 29.7 mU/g) as compared to rabbit
      lungs (741 +/- 67 mU/g). Whereas global cerebral ischemia/reperfusion did not
      increase MPO activity in rat brain (18.1 +/- 26.1 mU/g), intravenous infusion of
      cobra venom factor (1,447 +/- 407 mU/g) or endotoxin (1,439 +/- 285 mU/g),
      enhanced MPO activity in rabbit lung. These results parallel microcirculatory
      data from the organ surface. Therefore they supplement the intravital microscopic
      observations by demonstrating that these are indeed representative of deeper
      parenchymal tissue areas.

PMID- 8737713
TI  - Effects of Ginkgo biloba extract (EGb 761) on arteriolar spasm in a rat cremaster
      muscle preparation.
AB  - The effects of an extract of Ginkgo biloba (EGb 761) on arteriolar spasm were
      confirmed using a preparation of rat cremaster muscle. When vasospasm was induced
      by rat serum, arteriolar constriction reached 25-30% of the initial diameter
      after 10 min. Intravenous injection of EGb 761 (30 mg/kg) 5 min after inducing
      spasm inhibited about 80% of this serum-induced vasoconstriction. As previous
      studies have shown that EGb 761 has an antiaggregatory effect on platelets,
      thrombin, serotonin (platelet-derived compounds that are present in the serum)
      and a thromboxane analogue (U46619) were also used to induce vasospasm.
      Administration of EGb 761 (30 mg/kg) 5 min after exposure of the preparation to
      serotonin (10(-3) M) or 10 min after exposure to thrombin (20 units) did not
      affect vasospasm induced by these agents. In contrast, treatment with this same
      dose of EGb 761 5 min after exposure of the preparation to U46619 (10(-4) M)
      abolished the arteriolar constriction induced by this agent in 15 min. The
      thromboxane/prostaglandin H2 receptor antagonist SQ29548 antagonized serum
      induced vasospasm, indicating an involvement of thromboxane. Other experiments
      indicated that the effects of EGb 761 of counteracting vasospasm may be mediated
      in part by ginkgolide B, a triterpene constituent of the extract that is an
      antagonist of platelet-activating factor and in part by an 'NO-like' action of
      its proanthocyanidin constituents. Taken together, these results have revealed
      that EGb 761 treatment can antagonize the vasoconstrictor effect of thromboxane
      on arterioles. As thromboxane is implicated in many cardiovascular disorders,
      this property of EGb 761 may explain some of its beneficial clinical effects in
      such pathologies.

PMID- 8737714
TI  - Effects of rat hepatocytes on macromolecular permeability of bovine aortic
      endothelial cell monolayer.
AB  - The aim of this study was to examine whether the hyperpermeable structure of the
      liver endothelium in vivo is related to the interactions of hepatocytes in a
      culture system. The permeation of macromolecular FITC-labeled dextran (molecular
      weight 70,000) through a monolayer of bovine aortic endothelial cells (BAEC),
      cocultured with rat parenchymal hepatocytes (P-hep), was increased. When the BAEC
      were cocultured with nonparenchymal hepatocytes (N-hep), the permeability of the
      BAEC monolayer was not increased. However, when the BAEC were cocultured with a
      mixture of P-hep and N-hep (PN-hep), the BAEC monolayer was more permeable than
      when BAEC were cocultured with P-hep alone. The conditioned medium of P-hep did
      not alter the BAEC monolayer permeability, nor did the extracellular matrix of P
      hep alter BAEC permeability. When the BAEC were cocultured with PN-hep, the F
      actin content was not altered. These findings suggest that the interaction
      between hepatocytes and endothelial cells exerts an important effect on the
      hyperpermeable structure of the liver vessels in vivo.

PMID- 8737715
TI  - Management of the Hughes syndrome.

PMID- 8737716
TI  - Microheterogeneity of alpha 1-antitrypsin in relation to the concentration of its
      complex with immunoglobulin A in the sera of patients with rheumatoid arthritis.
AB  - OBJECTIVE: Serum alpha 1-antitrypsin (alpha 1AT) is an acute-phase glycoprotein
      which contains three carbohydrate side chains, N-glycosidically linked to the
      asparagine molecules (Asn46, Asn83 and Asn247) of the single polypeptide unit.
      "Microheterogeneity", which is a varying proportion of bi- or triantennary
      heteroglycans attached to the glycosylation sites, has been observed in various
      inflammatory states including rheumatoid arthritis (RA), and may influence the
      properties of alpha 1AT. METHODS: In this study, we used affinity
      immunoelectrophoresis with the lectin concanavalin A (ConA) to investigate the
      possible role of alpha 1AT microheterogeneity in IgA-alpha 1AT complex formation.
      The concentrations of alpha 1AT and its glycosylation variants, the level of
      immunoglobulin A (IgA), and concentration of IgA-alpha 1AT complex were
      determined in the sera of 43 patients with RA. RESULTS: In seven patients, high
      concentrations of the IgA-alpha 1AT complex were found. This group did not differ
      from the remaining patients in sex, age, or disease activity. However,
      significantly higher concentrations of both the alpha 1AT variant 1a+1b (with a
      predominance of triantennary heteroglycan side chains) and IgA were found in
      patients with an elevated complex compared to those with low serum levels of IgA
      alpha 1AT complex (p < 0.05 for both variables). In the entire group, there was a
      significant correlation between the IgA-alpha 1AT complex level and both serum
      IgA and the concentrations of alpha 1AT variants 1a+1b and 2 (r = 0.3473, p <
      0.05; r = 0.4604, p < 0.005; r = 0.3176, p < 0.05, respectively). CONCLUSION: The
      results suggest that the microheterogeneity of alpha 1AT may play a part in the
      formation of the IgA-alpha 1AT complex in RA.

PMID- 8737717
TI  - CD4 cytopenia and occasional expansion of CD4+CD8+lymphocytes in Sjogren's
      syndrome.
AB  - OBJECTIVES: To define whether Sjogren's syndrome (SS) patients have
      lymphocytopenia compared to healthy controls, and to assess which lymphocyte
      subset might be involved. The presence of any concurrent infection was recorded.
      METHODS: A cohort of ten consecutive patients with SS was studied, and the
      results were compared with ten sex- and age-matched controls (C). RESULTS: In SS,
      a significant cytopenia of CD4+ (679 +/- 339 vs 1110 +/- 222 cells/mm3, p <
      0.005) and an even more impressive decrease in the CD4+CD45 RA+ (242 +/- 154 vs
      491 +/- 190 cells/mm3, p < 0.005) subset was observed. An absolute CD4
      lymphocytopenia (CD4+ < 300 cells/mm3) was seen in two patients. In one patient
      an unusual finding was the expansion of a double positive population of CD4+CD8+
      lymphocytes. No striking relationship with any particular infection was shown. A
      retrospective review of the absolute CD4+ cytopenia in 54 consecutive SS cases
      revealed a prevalence of 5.5%. CONCLUSION: Some SS patients have T
      lymphocytopenia which mainly affects the CD4+CD45 RA+ subset. Occasional cases
      with absolute CD4 lymphocytopenia may also be observed. These patients show some
      evidence of mild recurrent or chronic, but never severe, opportunistic
      infections.

PMID- 8737718
TI  - A study of sixty pregnancies in patients with the antiphospholipid syndrome.
AB  - OBJECTIVE: To study the maternal and fetal outcome in treated antiphospholipid
      syndrome (APS) pregnancies. METHODS: Sixty pregnancies in 47 APS patients (11
      primary and 36 secondary) were followed in a multidisciplinary clinic. Patients
      testing antiphospholipid antibody positive and having a history of recurrent
      miscarriages were treated with low-dose aspirin (75 mg) daily. Patients with APS
      and a previous history of thrombotic events were treated with subcutaneous
      unfractionated or low molecular weight heparin and low-dose aspirin (75 mg)
      daily. RESULTS: The live birth rate increased from 19% of their previous non
      treated pregnancies to 70% despite a high incidence of obstetric and fetal
      complications: pre-eclampsia (18%), prematurity (43%), fetal distress (50%) and
      intrauterine growth retardation (31%). Two predictors of fetal outcome were
      observed: the previous obstetric history and the presence of thrombocytopenia.
      Seven pregnancies (12%) were complicated by thrombotic events during pregnancy or
      during the puerperium. There were no thrombotic events in those receiving a low
      molecular weight heparin regimen. CONCLUSION: Close obstetric monitoring by a
      multidisciplinary team and the use of antithrombotic therapy was effective in
      reducing the fetal wastage in APS pregnancies despite a high incidence of
      obstetric and fetal complications.

PMID- 8737719
TI  - The reactivity of sera from patients with systemic lupus erythematosus to seven
      different species of single and double stranded deoxyribonucleic acids.
AB  - OBJECTIVE: Anti-DNA antibodies are frequently found in the serum of patients with
      systemic lupus erythematosus (SLE). To understand whether the avidity of SLE sera
      to different species of single-stranded (ss) and double-stranded (ds) DNA is
      different or not, the reactivity of active SLE sera to seven species of DNA from
      viral, bacterial, piscine, and mammalian sources was compared. METHODS: Nineteen
      sera from patients with active SLE were studied for their reactivity to different
      ssDNA and dsDNA from Escherichia coli (EC), Micrococcus lysodeikticus (ML),
      Clostridium perfringens (CP), calf thymus (CT), salmon testis (ST), human
      placenta (HP) and lambda phage by ELISA. The dsDNA was purified by treating it
      with S1 nuclease and proteinase K, followed by Sephacryl S-300 gel filtration.
      The ssDNA was purified by absorption on a hydroxyapatite column after heat
      cleavage of the dsDNA. RESULTS: The reactivity of SLE sera to 7 species of dsDNA
      was not significantly different and they recognized a more widely shared epitope.
      In contrast, the reactivity of these sera to 7 species of ssDNA was erratic and
      the antigens could be grouped into high (CP and HP), medium (EC, ML, CT, and ST)
      and low (lambda-phage) antigenicities. CONCLUSION: The anti-ssDNA and anti-dsDNA
      antibodies of SLE patients recognize more widely shared determinants on the DNA
      of seven different species. Lambda-phage DNA shows the poorest immunogenicity
      among them.

PMID- 8737720
TI  - Cyclosporine A shows immunosuppressor activity on T lymphocytes from the
      peripheral blood and synovial fluid of patients with autoimmune arthritis.
AB  - OBJECTIVE: This work studies the effects of Cyclosporine A (CsA) upon the
      activation and proliferation of mononuclear cells (MNC) from the peripheral blood
      (PB) of patients with chronic autoimmune arthritis and from healthy controls, and
      from the synovial fluid (SF) of patients. METHODS: In vitro studies of
      activation, proliferation, mRNA expression and lymphokine production were carried
      out. RESULTS: We found in the PB and SF MNCs from patients with autoimmune
      arthritis that CsA inhibits the proliferative response, activation antigen
      expression, IL-2 mRNA expression and IL-2 production induced by polyclonal
      mitogens in a dose dependent manner. CONCLUSION: CsA blocks lymphocyte activation
      in PB and SF MNCs from patients with autoimmune arthritis.

PMID- 8737721
TI  - Different cytokine profiles in the synovial fluid of patients with
      osteoarthritis, rheumatoid arthritis and seronegative spondylarthropathies.
AB  - OBJECTIVE: Cytokines play a critical role in the pathogenesis of arthritis. The
      aim of this study was to compare the amounts of IL-1 alpha, IL-1 beta, IL-4, IL
      6, IL-8, IL-10, IL-12, TNF-alpha, TGF-beta 1 and IFN-gamma in the synovial fluid
      of 30 patients with rheumatoid arthritis (RA), 40 patients with osteoarthritis
      (OA) and 13 patients with seronegative spondylarthropathies (SpA). METHODS: Since
      some samples exhibited non-specific activities, all cytokines were measured by
      ELISA in the presence or absence of cytokine specific neutralizing antibodies.
      RESULTS: Our data show that these cytokines can be detected in OA, RA and SpA.
      Compared to patients with OA, all cytokines were found in higher levels in
      patients with RA and SpA. Surprisingly, higher levels of IL-4, IL-10 and TGF-beta
      1 were not associated with lower cytokine levels. In contrast, higher levels of
      IFN-gamma were associated with elevated monokine concentrations. CONCLUSIONS: Our
      data indicate that the immunosuppressive effects of IL-4, IL-10 and TGF-beta 1
      predicted from in vitro studies may not be active in vivo. Different monokine
      profiles could be observed in patients with IL-4 and/or IFN-gamma, indicating
      that the T cells involved in these diseases may have different immunoregulatory
      properties.

PMID- 8737722
TI  - Anti-endothelial cell antibodies in patients with various forms of vasculitis.
AB  - OBJECTIVE: To determine the prevalence of anti-endothelial cell antibodies (AECA)
      in various forms of vasculitis and to evaluate their relationships with markers
      of endothelial cell (EC) injury such as thrombomodulin (TM), von Willebrand
      factor antigen (vWf) and protein S. METHODS: A total of 167 disease-associated
      sera, from 79 patients with large- or medium-sized (group I) and 88 with small
      sized vessel vasculitis (group II), were examined for the presence of AECA using
      a cellular enzyme-linked immunosorbent assay (ELISA). These were evaluated before
      and after incubation with epithelial cells. EC plus epithelial cell (eC) extracts
      were fractionated and blotted with selected sera, and EC plus mononuclear cell
      extracts were dotted and blotted with lupus sera. Soluble TM, vWf and protein S
      levels were measured by ELISA. RESULTS: The binding of antibodies to eC was
      significant in group II sera (p < 0.01) but not in group I sera, so that the
      remaining EC-specific activity was significantly higher (p < 0.001) in the latter
      group than in the former. Eight antigenic specificities appeared to be specific
      for EC, whereas three were shared with eC. Despite absorption, the sera remained
      as reactive with EC and MNC as before. Taking the patient group as a whole, the
      levels of serum TM correlated with the titers of IgG, IgM and IgA AECA.
      CONCLUSION: EC-specific activity is more often encountered in group I than in
      group II patients. At present, the explanation for the distinct AECA
      specificities in these disease associated sera is not clear.

PMID- 8737723
TI  - Comparison of MRI and computed tomography in the various stages of plasma cell
      disorders: correlations with biological and histological findings. Myelome-Midi
      Pyrenees Group.
AB  - OBJECTIVE: Our study had a double aim: (i) to evaluate the sensitivity and the
      specificity of computed tomography (CT) and magnetic resonance imaging (MRI) in
      the different stages of plasma cell disorders, and (ii) to correlate CT and MRI
      with the biological, cytological and histomorphometric parameters. METHODS:
      Twenty-four patients with MGUS according to Kyle, 12 patients with stage 1 and 12
      with stage 3 myeloma, and 30 age-matched controls underwent MRI (sagittal views
      of the spine and coronal views of pelvis and femurs), CT (axial views from T10 to
      L5, sacrum, iliac crests), a histomorphometric study, determination of plasmocyte
      infiltration, and measurement of paraprotein, B2-microglobulin, the ca/cr ratio
      and osteocalcin. RESULTS: Heterogeneous osteopenia with microlacunae seen on CT
      scan and diffuse decreased signal intensity which remained higher than the signal
      of the intervertebral disk on T1 weighted sequences (MRI) were not peculiar to
      myeloma. Lacunae larger than 5 mm with trabecular disruption observed on CT,
      diffuse decreased signal intensity lower than the disk signal, and a multinodular
      appearance on MRI, not seen in the controls or in patients with MGUS, were
      observed in all stage 3 myeloma and in 40% of stage 1 myeloma patients. MGUS and
      stage 1 myeloma patients with abnormal MRI had a higher monoclonal component,
      plasma cell percentage and hypercellular bone marrow than those with normal MRI
      findings. MGUS or stage 1 myeloma patients with abnormal CT had a lower
      trabecular bone volume than those with normal CT. CONCLUSIONS: CT and MRI both
      reveal specific lesions in 40% of stage 1 myeloma patients. These methods are
      thus complementary in bone and bone marrow studies in myeloma.

PMID- 8737724
TI  - The stimulation of mononuclear cells from patients with rheumatoid arthritis to
      degrade articular cartilage is not modulated by cartilage itself.
AB  - OBJECTIVE: To study the modulation of mononuclear cell (MNC) activity in patients
      with rheumatoid arthritis (RA) by constituents released from human articular
      cartilage, which may be present in vivo during early events of the disease, when
      articular cartilage is not only mildly damaged. METHODS: In an attempt to
      stimulate RA MNC, cells were co-cultured with healthy or mildly damaged articular
      cartilage tissue. In addition, because of the reported cross-reactivity between
      cartilage constituents and mycobacterial heat-shock protein (hsp60), RA MNC
      sensitized with hsp60 were also co-cultured with cartilage tissue. Activation of
      the RA MNC was assessed by analysing the production of catabolic factors involved
      in joint damage. For this purpose culture supernatants of the treated RA MNC,
      comprising the catabolic factors, were added to freshly isolated articular
      cartilage explants. As a read out for catabolic activity, proteoglycan (PG)
      turnover by the explants was determined. RESULTS: Spontaneous activity of
      untreated RA MNC caused inhibition of PG synthesis and increased PG release upon
      addition of their culture supernatants to the cartilage explants. This MNC
      activity was not enhanced by the constituents released from healthy or mildly
      damaged cartilage tissue, whereas sensitization of RA MNC with hsp60 resulted in
      a 40% enhanced inhibition of PG synthesis. However, even under these pre
      activated conditions no reactivity towards the cartilage constituents could be
      observed. CONCLUSION: Cartilage constituents released from mildly damaged
      cartilage tissue, as may be present during the early events of RA. do not
      modulate the catabolic activity of RA MNC.

PMID- 8737725
TI  - HSP70-1 promoter region alleles and susceptibility to rheumatoid arthritis.
AB  - The distribution of HSP70-1 promoter alleles was studied in 90 adult Caucasian RA
      patients (65 European and 25 Asian Indian) and 113 normal control (60 European
      and 53 Asian Indian). The HSP70-1 promoter alleles were defined by
      oligonucleotide typing of polymerase chain (PCR)-amplified genomic DNA. The
      prevalence of HSP70-1 promoter allele "B" was significantly (p < 0.0004, pc <
      0.0012; RR = 5.1) higher in RA patients (22.2%) compared to normal controls
      (5.3%). It is likely therefore that HSP70-1 promoter allele B is associated with
      susceptibility to RA.

PMID- 8737726
TI  - Coexisting polyostotic fibrous dysplasia and Paget's disease.
AB  - The following case report describes a patient who is known to have both fibrous
      dysplasia and Paget's disease, and traces his history over more than 50 years.
      The similarities and differences between the two conditions and their relative
      importance at the various stages of the history are discussed.

PMID- 8737727
TI  - Iatrogenically induced vertebral osteomyelitis due to Pseudomonas aeruginosa.
AB  - We report three cases of iatrogenically induced vertebral osteomyelitis due to
      Pseudomonas aeruginosa. One case was a post-nucleotomy and post-operative
      complication of herniated disk treatment, one was related to infection of an
      epidural catheter in a patient suffering from rheumatoid arthritis and the third
      followed urinary investigation in a patient with prostate cancer. Infection was
      cured in all patients with antibiotic treatment. These case reports shed light on
      the possibility of infections with pseudomonas aeruginosa, in addition to the
      more common infections such as by staphylococci, especially following iatrogenic
      maneuvers.

PMID- 8737729
TI  - Glucocorticoid-induced osteoporosis: pathogenesis, prevention and treatment.
AB  - Glucocorticoids (GC) are widely used for anti-inflammatory and immunosuppressive
      therapy. Thirty to 50% of GC-treated patients develop osteoporosis. Potential
      mechanisms of GC-induced osteoporosis (GC-OP) include abnormalities in calcium
      balance, vitamin D metabolism, parathyroid hormone release and activity,
      prostaglandin E2 and cytokine synthesis, interference with c-fos and p-53
      expression in osteoblasts, and hypogonadism. Early diagnosis and detection of
      patients at risk are accomplished with rapid, safe and non-invasive bone density
      measurements. Preventive measures include maintaining a positive calcium balance,
      vitamin D supplementation (if indicated) and treatment of hypogonadism. The
      shortest duration and the smallest doses possible of GC for a particular
      condition are advisable. For high-risk patients and those with established GC-OP
      calcitonin or bisphosphonate therapy is recommended.

PMID- 8737728
TI  - Bone involvement in Gaucher's disease: 'bone crisis' or disease complication?
AB  - Bone involvement can represent the inaugural symptom of Gaucher's disease (GD).
      Here, we report the case of a 68-year old man diagnosed as having GD since 1963.
      In June 1994 the patient was referred to our Rheumatology Unit because of a long
      lasting coxalgia on the left hip and progressive walking impairment following
      traumatic fracture of the left femur. Multicystic osseous changes at standard X
      ray and hyper-gamma-globulinemia with an elevated ESR (122 mm, 1st hour)
      suggested the diagnosis of either osteonecrosis of the femoral head or multiple
      myeloma. On bone marrow biopsy examination, Gaucher's cell infiltrates were
      detected and an increased uptake in the distal left femur and proximal tibia were
      demonstrated by lipophilic tracer scan (99mTc-Sestamibi). Subsequently, the
      patient suffered another femoral fracture at a site of Gaucher's infiltrates
      previously documented by bone scan. We conclude that in patients with GD, 99mTc
      Sestamibi bone scan can selectively evaluate the presence of bone lipid deposits,
      and could indirectly differentiate this bone condition from other serious
      skeletal complications of the disease.

PMID- 8737730
TI  - Polyarticular pigmented villonodular synovitis associated with multiple
      congenital anomalies. A case of Noonan-like/multiple giant cell lesion syndrome.
AB  - A case of polyarticular pigmented villonodular synovitis associated with many
      congenital phenotypic peculiarities (such as shortness, blue sclerae, flattened
      nose, low-set ears, hypertelorism, curly hair and pulmonary stenosis) is
      described. The presence of many of the typical signs of the Noonan syndrome and
      the histological finding of giant cells on the synovial biopsy led to the
      diagnosis of Noonan-like/multiple giant cell lesion syndrome.

PMID- 8737731
TI  - Prevalence of anti-neutrophil cytoplasmic antibodies (ANCA) in juvenile chronic
      arthritis.
AB  - OBJECTIVE: Sera from 66 children with active JCA of oligoarticular, polyarticular
      or systemic onset, 13 sera from patients in disease remission, 15 sera from
      patients with reactive arthritis, and 11 from Lyme arthritis patients were tested
      for the presence of anti-neutrophil cytoplasmic antibodies (ANCA) in order to
      evaluate their diagnostic significance in JCA. RESULTS: ANCA were found in 21%
      (14/66) of the active JCA sera, all showing an atypical pANCA staining pattern
      using indirect immunofluorescence on ethanol fixed granulocytes. 71% of these
      sera also showed antinuclear antibodies (ANA) on HEp-2 cells. By additional
      staining on paraformaldehyde fixed granulocytes to exclude staining artefacts due
      to ethanol fixation, 2 of the pANCA positive sera showed cytoplasmic staining. In
      no case did we find nuclear fluorescence suggesting a true cytoplasmic
      localization of the involved antigens. All ANCA positive sera were negative for
      anti-MPO and anti-LF antibodies. ANCA prevalence in our study group did not
      correlate with the disease subgroup, disease duration or other clinical
      characteristics. However, we found ANCA only in active disease. CONCLUSION: Our
      data suggest that the diagnostic importance of ANCA in JCA is restricted to only
      a few JCA patients. In these cases, however, ANCA positivity supports the
      diagnosis of JCA. Further studies are needed to substantiate this finding, as
      well as possible subgroup specificities. Standardized techniques of granulocyte
      fixation and antigen specific tests are needed to produce comparable results in
      different study groups.

PMID- 8737733
TI  - Mixed cryoglobulinemia: effect of alpha-interferon on subclinical lymphocyte
      alveolitis.

PMID- 8737732
TI  - Transient disappearance of serum antiphospholipid antibodies can also be due to
      prednisone therapy.

PMID- 8737734
TI  - Bone infarcts or chondrosarcomas? The usefulness of MRI.

PMID- 8737735
TI  - Treatment of panniculitis with cyclosporin A.

PMID- 8737736
TI  - Polymyalgia rheumatica in the young female as a syndrome of presentation of
      Takayasu's arteritis.

PMID- 8737737
TI  - High urinary neopterin levels in Familial Mediterranean Fever.

PMID- 8737738
TI  - Hypophosphatemic osteomalacia in an elderly patient with generalized bone pain.

PMID- 8737739
TI  - Watermelon stomach in a patient with vitiligo and systemic lupus erythematosus.

PMID- 8737740
TI  - Systemic lupus erythematosus presenting as iron deficiency anemia due to
      pulmonary alveolar hemorrhage.

PMID- 8737741
TI  - Impact of genomics on inflammation research.

PMID- 8737742
TI  - Dithiocarbamates inhibit IL-1-induced cartilage degradation in bovine articular
      cartilage explants.
AB  - Interleukin-1-stimulated cartilage degradation in bovine articular cartilage
      explants is effectively inhibited by several different dithiocarbamates with
      IC50's in the micromolar range.

PMID- 8737743
TI  - Effect of manoalide on human 5-lipoxygenase activity.
AB  - The marine natural product manoalide (MLD) has been described to inactivate
      phospholipase A2 (PLA2) from several sources as well as to inhibit synthesis of
      eicosanoids in human polymorphonuclear leukocytes (HPMNL). MLD also reduces
      chemically-induced inflammation in vivo. In this investigation we have examined
      the effect of MLD on A23187-induced generation of leukotriene B4 (LTB4) and
      thromboxane B2 (TXB2) in HPMNL as well as 5-lipoxygenase (5-LO) activity from
      HPMNL sonicated preparations. In the intact cell system, MLD inhibited with
      similar potency biosynthesis of LTB4 and TXB2 (IC50 1.7 and 1.4 microM,
      respectively). In order to discern if inhibition of 5-LO is involved in the
      effect of MLD, we examined the action of this compound on 5-LO activity from
      10,000 x g and 100,000 x g supernatants of sonicated HPMNL homogenates. The
      enzymatic activity was not affected at concentrations of MLD up to 50 microM.
      These data indicate that MLD is not a direct inhibitor of 5-LO activity from
      HPMNL and support the hypothesis that its anti-inflammatory action could be
      related with a reduction of eicosanoid biosynthesis via inhibition of PLA2.

PMID- 8737744
TI  - Inhibition of endothelial cell adhesion molecule expression with SJC13, an
      azaindolidine derivative, in vitro.
AB  - Stimulation of cultured human umbilical vein endothelial cells (HUVEC) with
      lipopolysaccharide (LPS) induces adherences for human promyelocytic cell line
      HL60. Adherence of HL60 cells to HUVEC stimulated with LPS for 4h was completely
      inhibited by pretreatment with SJC13, an azaindolidine derivative. The mechanism
      whereby SJC13 inhibits the adhesiveness of HUVEC was investigated. Pretreatment
      of SJC13 inhibited LPS-induced expression of E-selectin and vascular cell
      adhesion molecule-1 (VCAM-1), but not intercellular adhesion molecule-1 (ICAM-1),
      in HUVEC, determined by flow cytometry and cellular enzyme-linked immunosorbent
      assay (cell-ELISA). The inhibitory activity was concentration dependent between
      62.5 and 1,000 micrograms/ml. SJC13 also selectively inhibited LPS-induced
      increases in E-selectin and VCAM-1 mRNAs, indicating that the action of SJC13 is
      to inhibit synthesis of these molecules. These data demonstrate that SJC13 is
      capable of selectively inhibiting the expression of E-selectin and VCAM-1, but
      not ICAM-1, in endothelial cells.

PMID- 8737745
TI  - Gold salts inhibit osteoclastic bone resorption in vitro.
AB  - Loss of bone mass is commonly associated with rheumatoid arthritis (RA) and is
      increasingly considered to be due to the increased activity of bone-resorbing
      osteoclasts. Gold salts such as auranofin (AF), aurothioglucose (ATG) and
      aurothiomalate (ATM) have beneficial therapeutic effects in RA, but their
      mechanisms(s) of action is not well understood. In the present study we have
      examined the effects of these 3 gold salts on osteoclastic bone resorption in
      vitro, using the bone slice assay where bovine cortical bone slices are resorbed
      by osteoclasts disaggregated from the long bones of neonatal rats. All 3 gold
      salts inhibited osteoclastic bone resorption with IC50 values of AF = 0.1
      microgram/ml, ATG and ATM = 1 microgram/ml. All 3 compounds caused a decreased
      survival of osteoclasts on bone slices at high concentrations indicating a
      cytotoxic effect that was also observed in a cytotoxicity assay with osteoblast
      like UMR-106 cells. Preincubation of bone slices with various concentrations of
      AF followed by extensive washing prior to use in the bone slice assay also
      resulted in an inhibition of bone resorption (IC50 = 4 micrograms/ml) and
      osteoclast survival on the bone slices preincubated with high concentrations of
      AF was decreased. Since these effects were obtained with therapeutic
      concentrations of gold salts, these results indicate that inhibition of
      osteoclastic bone resorption by gold salts may, at least in part, account for
      their beneficial effects in RA.

PMID- 8737746
TI  - Decrease of ciliary beat frequency by platelet activating factor: protective
      effect of ketotifen.
AB  - The ciliary beat frequency (CBF) of the tracheal epithelial cells controls in
      part the respiratory tract mucociliary transport efficiency. We investigated the
      effects on CBF of PAF-acether (PAF) and its metabolite/precursor lyso-PAF. Guinea
      pig tracheal rings were incubated for 3 to 6h with 1 microM PAF (C16, C18,
      C16/C18: 80/20%), lyso-PAF C16 or lyso-phosphatidylcholine (LPC). CBF changes
      were assessed by microphotooscillography (mean number of measures per ring = 14).
      We also examined the effect on PAF-induced CBF changes of the PAF receptor
      antagonist WEB 2086, the anti-asthmatic/anti-anaphylactic drug ketotifen and the
      anti-histamine H1 pyribenzamine. CBF of control rings exposed to vehicle only
      from 0 to 6h showed no significant statistical variations (hertz, mean +/- SEM):
      10.8 +/- 0.1 (n of measures = 890). By contrast, 1 microM C16, C18, and C16/C18
      PAF significantly inhibited CBF after 3 to 6h incubation. C16 and C16/C18 PAF
      were more potent than C18 PAF (8.8 +/- 0.2, n = 112, 8.7 +/- 0.2, n = 64, and 9.6
      +/- 0.1, n = 537 respectively; ANOVA analysis, p < 0.001 from control). At the
      same concentration, lyso-PAF also inhibited CBF, 9.5 +/- 0.1 (n = 197, p < 0.001)
      but not LPC, 10.5 +/- 0.2 (n = 127). WEB 2086 inhibited lyso-PAF and C16/18 PAF
      induced CBF decrease. Preincubation (20 min) with ketotifen but not with
      pyribenzamine (1 microM) also suppressed the CBF inhibitory effect of PAF and
      lyso-PAF. Incubation of [3H]PAF with tracheal rings from 10 min to 6h resulted in
      its partial metabolism (25%) into [3H]lyso-PAF and a compound with a short
      retention time (10 min). [3H]lyso-PAF incubated for 3h with tracheal rings was
      partially metabolized (10%) into [3H]PAF and a compound with a short retention
      time. The PAF-induced decrease of CBF is congruent with its influence on
      pulmonary clearance, possibly via a specific receptor, since WEB 2086 abolished
      the effect of PAF. The inhibition of the PAF-induced CBF decrease by ketotifen
      may contribute to the therapeutic properties of this antiallergic drug.

PMID- 8737747
TI  - Characterization of a primate model of asthma using anti-allergy/anti-asthma
      agents.
AB  - The following study was performed to further characterize a primate model of
      asthma using classes of drugs that target allergy (pyrilamine, cetirizine), are
      bronchodilators for the treatment of asthma (salbutamol, salmeterol) or are anti
      inflammatory (dexamethasone). These drugs were examined for their ability to
      inhibit acute, antigen-induced bronchoconstriction, the development of airway
      hyperresponsiveness (AHR) and the infiltration of leukocytes into the lungs of
      atopic cynomolgus monkeys (Macaca facsicularis) using a 10-day, multiple antigen
      (Ag) challenge protocol. All compounds except dexamethasone and cetirizine
      significantly (p < 0.05) reduced acute, Ag-induced bronchoconstriction
      (salbutamol: 74.2%, salmeterol: 52.6%%, pyrilamine: 62.4% inhibition) compared to
      vehicle control trials. Only dexamethasone and salmeterol prevented the
      development of AHR to methacholine challenge by 90.4 +/- 6.81% and 85.7 +/- 5.61%
      respectively. Dexamethasone significantly reduced the Ag-induced increase in BAL
      eosinophils by 85.9 +/- 8.53%. Cetirizine reduced the eosinophil response in 5 of
      6 monkeys and salmeterol demonstrated a trend towards reduced eosinophil
      increases after multiple Ag challenge, but neither of these were statistically
      significant. These results further illustrate the utility of this model in
      predicting compound effects against several relevant functional endpoints that
      are consistent with the effects of similar classes of compounds in humans.

PMID- 8737748
TI  - Human whole blood assays for inhibition of prostaglandin G/H synthases-1 and -2
      using A23187 and lipopolysaccharide stimulation of thromboxane B2 production.
AB  - When freshly drawn, heparinized human whole blood is incubated with 50 microM
      calcium ionophore A23187, platelets are stimulated to produce thromboxane B2
      (TxB2) by activation of prostaglandin G/H synthase-l (PGHS-1). TxB2
      concentration, as measured by immunoassay, is maximal at 20-30 min and declines
      thereafter. Addition of acetylsalicylic acid (IC50 = 2.8 microM) or other
      nonsteroidal antiinflammatory drugs (NSAIDs) 15 min or 4.5h prior to 30 min
      stimulation with ionophore results in concentration dependent inhibition of TxB2
      production. When blood is incubated with 0.01-10 micrograms/ml E.
      colilipopolysaccharide (LPS), PGHS-2 is induced and TxB2 levels become detectable
      at 3h and continue to increase through 24h. Using a 5h incubation with 10
      micrograms/ml LPS, aspirin (10 microM added at 0 h), which is rapidly metabolized
      to salicylic acid, had no effect on 10 micrograms/ml LPS-induced TxB2, but
      inhibited TxB2 production by ionophore A23187 added at 4.5h through acetylation
      of pre-existing PGHS-1. In a 5h assay, NSAIDs added at 0 h were compared for
      inhibition of TxB2 production stimulated by addition of ionophore A23187 at 4.5h
      (PGHS-1), or by addition of LPS at 0 h (PGHS-2). Most NSAIDs were more potent
      against PGHS-1 than PGHS-2. Diclofenac, naproxen and flufenamic acid were
      equipotent or slightly selective for PGHS-2. Diflunisal and nimesulide were > 4
      fold selective for PGHS-2, and NS-398 was > 30-fold selective for PGHS-2.

PMID- 8737749
TI  - Nitric oxide enhances cyclooxygenase activity in articular cartilage.
AB  - Nitric oxide (NO) is a small messenger molecule synthesized by a family of
      enzymes, the nitric oxide synthases. Cyclooxygenases are a group of
      proinflammatory enzymes that release prostaglandins including prostaglandin E2
      (PGE2). Both nitric oxide synthase and cyclooxygenase are involved in the
      inflammatory cascade of arthritis. However, the relationship between these two
      enzymes and their products has not been explored in articular cartilage. Here we
      show that in cultured bovine chondrocytes and explants of human osteoarthritic
      cartilage both nitric oxide synthase and cyclooxygenase activities were induced
      by the inflammatory mediators, lipopolysaccharide, and interleukin-1 beta or
      tumor necrosis factor-alpha. When nitric oxide synthase activity was inhibited,
      PGE2, synthesis was inhibited. NO donors also induced PGE2 synthesis and NO
      scavengers inhibited cyclooxygenase activity. Taken together, these results
      support the concept that PGE2 synthesis is directly related to NO formation and
      that NO may modulate cyclooxygenase activity in articular cartilage.

PMID- 8737750
TI  - Protective activity of ketoprofen lysine salt against the pulmonary effects
      induced by bradykinin in guinea-pigs.
AB  - We investigated the capacity of ketoprofen lysine salt (KLS) to counteract the
      pulmonary effects of some mediators of airway inflammation. The protective effect
      of KLS and its R-isomer against bradykinin (BK) induced plasma extravasation in
      the airways and bronchoconstriction was evaluated in anaesthetized guinea-pigs,
      in parallel with the capacity of KLS to inhibit the production of thromboxane A2
      (TXA2). Moreover, we studied the ability of KLS to modulate leukotriene C4 (LTC4)
      and acetylcholine (ACH) induced bronchoconstriction and the associated production
      of TXA2. Nimesulide (NIM) was used as the reference compound. KLS dose
      dependently inhibited the bronchoconstriction and the associated production of
      TXA2 induced by BK, with closely related ID50 values of 31.2 and 34.0
      micrograms/kg i.v., respectively. The protection was evident 10 min after KLS
      administration and, at 100 micrograms/kg i.v., lasted up to 2h, Moreover, KLS
      dose-dependently inhibited the increase in capillary permeability induced by BK,
      with a potency (ID50 23.4 micrograms/kg i.v.) slightly higher than that shown
      against the bronchoconstriction. KLS also prevented the bronchoconstriction and
      TXA2 production triggered by LTC4, but not ACH induced bronchoconstriction. In
      all the models studied, KLS was about 10 times more potent than NIM. These data
      demonstrate the capacity of KLS to counteract the bronchoconstriction induced by
      BK and LTC4 and to a large extent the airway inflammation induced by BK. Blockade
      of prostanoid production is likely to account for this protective effect, since
      the R-isomer of KLS was devoid of significant activity.

PMID- 8737751
TI  - Once-daily gentamicin: translating theory into practice.
AB  - Gentamicin continues to have an important role in the treatment of serious
      bacterial infections. There is increasing interest in once-daily administration,
      which is more convenient than multiple-dose regimens. Animals studies and
      clinical trials suggest that once-daily administration is as efficacious and no
      more toxic for a variety of infections, but there is still some reluctance to use
      once-daily regimens routinely in neutropenic patients, because of the potential
      risk of breakthrough bacteraemia. A number of aspects of the serum concentration
      monitoring of once-daily gentamicin remain unresolved. The most commonly used
      assay systems are not sensitive enough, without some modification in technique,
      to detect the very small pre-dose concentrations seen with once-daily dosing, and
      it is not clear what constitutes an acceptable pre-dose concentration. Until the
      results from further studies become available, it is prudent to maintain a pre
      dose concentration below 1 mg.1(-1), and local arrangements are necessary to
      address the frequency and timing of assays. It seems likely that once-daily
      administration will become the norm, because of its many advantages.

PMID- 8737752
TI  - Efficacy and safety of spirapril, a new ace-inhibitor, in elderly hypertensive
      patients.
AB  - OBJECTIVE: To compare the safety, efficacy, tolerability and duration of the
      antihypertensive effect of an ACE-inhibitor spirapril 3 mg or 6 mg in elderly (>
      or = 60 y) hypertensive patients in a multicentre, observational, double-blind
      randomised study. METHODS: After a four-week placebo period, 39 patients were
      randomised to six weeks of treatment with spirapril 3 mg and 47 patients with
      spirapril 6 mg. RESULTS: In the sitting position the mean (SD) decrease in
      systolic blood pressure (SBP) was 12(15) mmHg (95% confidence interval 7 to 17
      mmHg) and in diastolic blood pressure (DBP) 10(7) mmHg (8 to 12 mmHg) in the 3-mg
      group and 10(13) mmHg (6 to 14 mmHg) and 9(7) mmHg (7 to 11 mmHg), respectively,
      in the 6-mg group (P < 0.001 compared to placebo period in both groups).
      Spirapril 3 mg and 6 mg produced DBP < or = 90 mmHg or a fall > or = 10 mmHg in
      53% and 51% of the patients, respectively. DBP was < or = 90 mmHg in 36% and SBP
      < or = 160 mmHg in 67% of the patients taking 3 mg and in 26% and 63% of the
      patients taking 6 mg spirapril. The most commonly reported adverse effects were
      cough (13-17%), dizziness, headache and insomnia. A trend to a more frequent
      adverse effects was observed in patients receiving spirapril 6 mg. Spirapril was
      both cholesterol- and glucose-neutral. CONCLUSIONS: According to our study,
      spirapril 3mg seems to be a suitable starting dose for the treatment of
      hypertension in the elderly patients.

PMID- 8737753
TI  - Is overuse of sumatriptan a problem? A population-based study.
AB  - OBJECTIVE: Sumatriptan is highly efficacious in aborting acute attacks of
      migraine. Owing to recent reports of misuse of sumatriptan, we performed a study
      of its use in a Danish population. METHODS: Data were retrieved from a
      prescription database covering a period of 27 months after release of the drug.
      Consumption was described by the defined daily dose (DDD) unit and total
      individual consumption during the period was calculated. Those who received more
      than one prescription for sumatriptan were classified according to peak use of
      sumatriptan into high (> or = 60 DDD/31 days) (n = 45), intermediate (30-59
      DDD/31 days) (n = 127) and low (< 30 DDD/31 days) (n = 1423) consumption groups.
      Individual usage of other medication was described. RESULTS: We identified 2,878
      users of sumatriptan, of whom 1,283 (45%) only redeemed one prescription. The use
      of sumatriptan was highly skewed. The 1% heaviest users accounted for 20% of the
      total consumption. The median total individual consumption of sumatriptan was 500
      DDD, 192 DDD, and 24 DDD in the three groups of multiple redeemers, respectively.
      Pronounced differences in the total amounts of opioids and ergot alkaloids used
      were also found, with the high peak consumption group being the heaviest
      consumers of all drug categories, although half of them had only received large
      doses of sumatriptan. Fifty seven % of high peak users redeemed more than 29 DDD
      of sumatriptan within one month of initiation of treatment. The 45 high peak
      users had received the bulk of their medication, largely in tablet formulation,
      from 31 prescribers. The data points to rebound headache as a plausible
      underlying mechanism, but incorrect use of sumatriptan for migraine prophylaxis
      is also a possibility. Overuse of sumatriptan has serious economic consequences
      and its long-term health effects are not known.

PMID- 8737754
TI  - Ketotifen in HIV-infected patients: effects on body weight and release of TNF
      alpha.
AB  - OBJECTIVE: Tumor necrosis factor alpha (TNF-alpha) is involved in the genesis of
      HIV-associated malnutrition. We performed an open-label trial on the effects of
      ketotifen, an in vitro inhibitor of TNF-alpha release from peripheral blood
      mononuclear cells (PBMCs), on the nutritional status and TNF-alpha release of HIV
      infected subjects. PATIENTS: Six HIV-infected subjects received oral ketotifen 4
      mg per day for 84 days and were followed up for an additional 70-day period. Body
      composition was measured by bioelectrical impedance analysis. TNF-alpha plasma
      levels, TNF-alpha release from PBMCs, and plasma concentration of soluble TNF
      receptors were measured repeatedly during the study and control period. RESULTS:
      During ketotifen intake, TNF-alpha release from stimulated PBMCs significantly
      decreased (68 vs 155 pg ml-1), but not TNF-alpha and soluble TNF receptor plasma
      concentrations. Subjects gained weight (+ 2.7 kg), whereas weight loss was
      observed after cessation of treatment (-1.6 kg). CONCLUSION: Ketotifen inhibits
      TNF-alpha release from stimulated PBMCs and might thus be useful in the
      management of HIV-associated malnutrition.

PMID- 8737755
TI  - Comparison of dose requirement, serum erythropoietin and blood pressure following
      intravenous and subcutaneous erythropoietin treatment of dialysis patients. IV
      and SC erythropoietin.
AB  - OBJECTIVE: The purpose of the study was to investigate the effect of route of
      administration of erythropoietin (EPO) on the dose requirement in dialysis
      patients after intravenous (IV) and subcutaneous (SC) therapy. METHODS: The study
      was performed as a single centre, prospective, open, combined parallel and cross
      over study of 50 dialysis patients, consecutively randomised to IV or SC
      treatment with EPO. The initial dose was 49 U.kg-1 3-times weekly, adjusted to
      increase haemoglobin (Hgb) from a median 5.3 mmol.1(-1) to a target of
      haemoglobin 6.5-7.5 mmol.1(-1). After reaching the target level, the haemoglobin
      was maintained for 4 months (Period 1). Then IV and SC treatment was switched for
      a further 4 months (Period 2). The study included high risk patients. The
      adjustment period was completed by 38 patients, Period one by 32 patients (IV/SC
      = 15/17; male/female = 19/13; age = 54 (24- 71) y), and Period two by 22
      patients. RESULTS: No significant difference was found between the two groups in
      the reticulocyte response, the rate of Hgb increase (IV 0.7 versus SC 0.5,
      mmol.1(-1). month-1), time to reach target level (IV 43 versus SC 60 days), or
      total EPO dose per increase in haemoglobin to target level (IV 663 versus SC 946
      (U.kg-1) per (mmol Hgb.1(-1)). The overall median maintenance dose during the
      last month of the two four month periods was 105 (range IV 51-336) U.kg-1.w-1 and
      SC 104 (range 21-321) U.kg-1.w-1. Through serum EPO levels were significantly
      higher during SC treatment. The blood pressure did not change significantly from
      the base level after either route of administration; start 133/80 versus 143/80
      mmHg, target 127/78 versus 154/85 mmHg, and maintenance period 140/84 versus
      142/85 mmHg. Thus, three-times weekly IV or SC EPO did not differ significantly
      in efficacy or in the effect on blood pressure in dialysis patients.

PMID- 8737756
TI  - Effects of oral contraceptives on plasma neutral amino acids and cholesterol
      during a menstrual cycle.
AB  - OBJECTIVE: Concentrations of plasma neutral amino acids, i.e. threonine, serine,
      asparagine, glycine, alanine, citrulline, alpha-aminobutyric acid, valine,
      methionine, isoleucine, leucine, tyrosine, phenylalanine, and tryptophan, and
      serum cholesterol, were determined at the follicular (Day 4), mid-cycle (Day 16)
      and luteal (Day 25) phases of the menstrual cycle in 15 users of the new
      generation of combined oral contraceptives (OC), 11 on multiphase combined OC,
      and 17 controls. RESULTS: The controls showed a decrease in the sum of amino
      acids to 95% at mid-cycle and 90% in the luteal phase relative to the follicular
      phase, and a significant decrease in the tyrosine level at the luteal relative to
      the follicular phase. Since there was no significant difference between the two
      OC subgroups in the levels of the specified variables at either of the phases,
      the two groups were considered together. The sum of amino acids in the OC group
      decreased to 89% at mid-cycle and 91% at the luteal phase relative to the
      follicular phase, indicating less metabolic effect than reported for older OC
      formulations. Compared to the controls, the OC group showed significant increased
      threonine level at the luteal phase, decreased glycine levels at mid-cycle and
      the luteal phases, decreased citrulline level at mid-cycle, and markedly
      decreased tyrosine levels at the mid-cycle and luteal phases. Neither total nor
      high density lipoprotein (HDL) cholesterol differed significantly between the
      control and OC groups. CONCLUSION: The results suggest that the metabolic effects
      of the new generation combined OC on neutral amino acids and cholesterol are only
      modest to slight, except for the effect on tyrosine, the brain noradrenaline
      precursor, which may cause disturbances of various noradrenaline-mediated central
      functions in susceptible subjects.

PMID- 8737757
TI  - Are there stereoselective electrophysiologic effects of intravenously
      administered (S)- or (R)-propafenone hydrochloride in patients with
      supraventricular tachycardia?
AB  - OBJECTIVE: The electrophysiological effects of intravenously administered pure
      (S)- and (R)-propafenone hydrochloride has been determined for the first time in
      humans-12 patients with supraventricular tachycardia. METHODS: Measurements were
      performed before and during drug therapy. RESULTS: (S)- and (R)-propafenone
      prolonged the AH interval from 82 to 107 ms and 75 to 84 ms, respectively, and
      significantly increased the V nodal Wenckebach cycle length by 58 ms and 37 ms,
      respectively. The AV nodal effective refractory period in both groups was
      increased significantly to the same extent (45 vs 42 ms). Sinus node recovery
      times were not significantly influenced by either enantiomers. Both (S)- and (R)
      propafenone significantly prolonged the HV interval to the same extent (from 41
      to 51 ms, and 42 to 53 ms). Changes in the electrophysiological characteristics
      of the myocardium were more pronounced in the atria than in the ventricles. Only
      (S)-propafenone significantly increased the atrial effective refractory period
      from 204 to 230 ms, and the ventricular effective refractory period from 225 to
      241 ms compared to (R)-propafenone (from 221 to 239 ms, and from 219 to 222 ms,
      respectively). There was a more pronounced electrophysiological effect on AV
      nodal conduction of (S)- than (R)-propafenone, probably as a result of its beta
      blocking activity. CONCLUSION: The electrophysiological effects of (S)-compared
      to (R)-propafenone were not very pronounced, so it still remains questionable
      whether one of the enantiomers might be clinically superior to the other, or to
      the racemic mixture.

PMID- 8737758
TI  - Adverse events with continuous doxapram infusion against late postoperative
      hypoxaemia.
AB  - OBJECTIVE: A randomized double-blind controlled trial of doxapram versus placebo
      against late postoperative hypoxaemia was planned to include 40 patients (2 x
      20). RESULTS: After inclusion of 18 patients a serious adverse event was
      encountered with development of a brain stem infarction in a 90-year-old woman
      receiving doxapram. At this point the randomization code was broken and we
      decided to terminate the trial. Three of nine patients receiving doxapram had had
      an adverse event whereas none of the patients receiving placebo had adverse
      events (P = 0.2). In the 18 patients studied, there was an insignificant trend
      towards higher mean oxygen saturation in the doxapram group, and a significantly
      higher minimum oxygen saturation and reduced number of hypoxaemic events on the
      first postoperative night. CONCLUSION: Although these preliminary data on the
      effect of doxapram on postoperative hypoxaemia seem promising, further studies on
      the effect of continuous nocturnal postoperative doxapram infusion on levels of
      arterial oxygen saturation should be postponed until more knowledge about the
      pharmacokinetics of doxapram in this particular clinical situation has been
      gathered.

PMID- 8737759
TI  - Investigation of nifedipine absorption in different regions of the human
      gastrointestinal (GI) tract after simultaneous administration of 13C- and 12C
      nifedipine.
AB  - OBJECTIVE: To evaluate the absorption of nifedipine in man from four different
      sites of the gastrointestinal tract. METHODS: On separate occasions, nifedipine
      solution was administered locally to the stomach, the small intestine and two
      sites in the colon in 4 healthy male volunteers (age 29-34 y weight 73-82 kg, non
      smokers) using a remote controlled drug delivery device (HF-capsule). In order to
      assess absolute and relative bioavailabilities, an intravenous infusion was given
      on a separate occasion and all treatments were accompanied by a simultaneous oral
      dose of a stable-isotope labelled nifedipine solution. This allowed to minimise
      the influence of intra-individual variability. Plasma samples were collected up
      to 24 h post dose and faeces for 72 h. A new method of analysis of nifedipine in
      plasma and faeces using gas chromatography with mass-selective detection (GCMS)
      was employed. RESULTS: Dissolved nifedipine was found to enter the systemic
      circulation completely along the intestine, being absorbed from jejunum to colon.
      Absorption was less rapid from the colon than from the upper part of the gut, but
      this was not associated with a decrease in absorption and/or bioavailability:
      Absolute bioavailability, calculated from the normalised AUC values, ranged from
      42 to 56%, and bioavailability relative to oral solution was 100 to 126% (medians
      of the application sites). CONCLUSION: The absence of an absorption window in the
      intestinal tract suggests that nifedipine is well suited for use in controlled
      release formulations.

PMID- 8737760
TI  - Pharmacokinetic interaction between cyclosporine and the dihydropyridine calcium
      antagonist felodipine.
AB  - OBJECTIVE: In a double blind, randomised, placebo-controlled, cross-over study 12
      healthy male volunteers were allocated to receive felodipine + placebo,
      cyclosporine + placebo, and felodipine + cyclosporine in order to investigate the
      interaction between the calcium channel blocker felodipine and cyclosporine as it
      affects the pharmacokinetics of felodipine, dehydrofelodipine, and cyclosporine,
      and 24-hour blood pressure measurements. METHODS: Single doses of cyclosporine
      (capsules, 5 mg/kg body weight) and of felodipine (extended release (ER) tablets
      10 mg) were given at a 1-2 week interval. Plasma drug concentrations were
      followed for 2 days after drug intake. RESULTS: For cyclosporine, Cmax was
      increased after combined treatment (16%) compared to cyclosporine alone, but
      felodipine did not influence other kinetic parameters of cyclosporine. For
      felodipine, combined treatment with cyclosporine and felodipine increased AUC and
      Cmax (58% and 151%, respectively) and lowered mean residence time (24%)
      significantly compared to felodipine alone. For the metabolite dehydrofelodipine,
      too, AUC and Cmax were increased after the combined treatment (43% and 94%,
      respectively). Mean 24-hour systolic and diastolic blood pressures were
      significantly lower after felodipine, both when felodipine was given alone
      (121/68 mmHg) and in combination with cyclosporine (122/68 mmHg) compared to
      cyclosporine alone (127/73 mmHg). CONCLUSION: A combined single dose of
      cyclosporine and felodipine in healthy subjects increased the AUC and Cmax of
      felodipine suggesting a cyclosporine-induced decrease in the first-pass
      metabolism of felodipine, whereas the AUC of cyclosporine was only slightly
      increased by felodipine.

PMID- 8737762
TI  - Intraindividual variability in red blood cell thiopurine methyltransferase
      activity.
AB  - OBJECTIVE: Long-term (13 weeks) and circadian (24 hours) intraindividual
      variability in red blood cell (RBC) thiopurine methyltransferase (TPMT) activity
      in healthy subjects was studied. METHODS: RBC TPMT activity was measured
      radiochemically. RESULTS: The variability in RBC TPMT activity was low and was
      only slightly higher than the imprecision of he TPMT assay. Mean long-term
      intraindividual variability in RBC TPMT activity was 6.5% (CV) (n = 46). Mean
      intraindividual circadian variability in RBC TPMT activity was 6.4% (CV) (n =
      18). CONCLUSIONS: In contrast to what has been observed in children with acute
      lymphoblastic leukaemia, the intraindividual variability in RBC TPMT activity in
      healthy subjects was low. The reported changes in baseline RBC TPMT activity in
      patients are probably therefore due to drugs, disease, assay variation or other,
      unidentified factors.

PMID- 8737761
TI  - In vitro comparative inhibition profiles of major human drug metabolising
      cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase
      inhibitors.
AB  - OBJECTIVE: The affinity of (+)-, (-)- and (+/-)- fluvastatin, a new synthetic HMG
      CoA reductase inhibitor developed as a racemate, for specific human P450
      monooxygenases in liver microsomes was compared with that of the
      pharmacologically active acidic forms of lovastatin, pravastatin and simvastatin.
      METHODS: Affinity was determined as the inhibitory potency for prototype
      reactions for 3 major drug metabolising enzymes: diclofenac 4'-hydroxylation
      (CYP2C9), dextromethorphan O-demethylation (CYP2D6), and midazolam 1'
      hydroxylation (CYP3A4). RESULTS: Lovastatin acid, pravastatin and simvastatin
      acid displayed moderate affinity for all three P450 isozymes (estimated Ki > 50
      micromol.1(-1)). Racemic and (+)- and (-)-fluvastatin showed moderate affinity
      (estimated Ki > 50 micromol.1(-1)) for CYP2D6 and CYP3A4, whereas their affinity
      for CYP2C9 was high (estimated Ki < 1 micromol.1(-1)). Diclofenac 4'
      hydroxylation was competitively and stereoselectively inhibited, with measured
      Ki's of 0.06 and 0.28 micromol.1(-1) for (+)- and (-)- fluvastatin, respectively.
      CONCLUSION: Fluvastatin selectively inhibits a major drug metabolising enzyme
      (CYP2C9), the (+)-isomer (pharmacologically more active) showing 4-5 fold higher
      affinity. As already reported for lovastatin and simvastatin, in vivo drug
      interactions by inhibition of liver oxidation of CYP2C9 substrates (e.g.
      hypoglyceamic sulphonylureas and oral anticoagulants) may be expected.

PMID- 8737764
TI  - Metabolic and analytical interactions of grapefruit juice and 1,2-benzopyrone
      (coumarin) in man.
AB  - OBJECTIVE: Grapefruit juice is known to inhibit mammalian cytochrome P450
      isozymes such as CYP3A4. The aim of this study was to investigate the influence
      of the juice on the fate of coumarin (1,2-benzopyrone) metabolized by CYP2A6 in
      man. Its potentially inhibitory effect was examined when low and high amounts of
      grapefruit juice were taken. METHODS: In crossover studies, doses of 10 mg
      coumarin (Venalot) were given orally to an healthy male volunteer. The drug was
      taken either with water or with grapefruit juice, at different volumes (300 ml or
      4 x 250 ml at intervals of 30 min). Urine samples were collected up to 24 h after
      dosing. After in vitro hydrolysis they were analysed fluorimetrically for
      umbelliferone, the metabolite of coumarin, and cumulative excretion curves were
      established. HPLC and TLC served to identify fluorescent metabolites from the
      juice. RESULTS: If coumarin is given in water its excretion is complete after 6 h
      and 70% of the dose is recovered. Grapefruit juice (300 ml) given simultaneously
      slightly retards the appearance of the fluorescent metabolite in the urine within
      the first few hours. The recovery of coumarin remains unaffected. One litre of
      juice enhances the delay and increases the recovery of coumarin to nearly 100%.
      Respective controls with grapefruit juice alone lead to remarkable excretions of
      a fluorescent material identified as conjugated scopoletin, which strongly
      interferes with the analysis of the coumarin experiment. The precursor of
      scopoletin is widely present at different concentrations in commercially
      available grapefruit juices. However, the autoinhibition of the juice is
      correlated neither to the concentration of naringin nor to that of scopoletin.
      CONCLUSION: Only grapefruit juice given at high doses (1 L) retards the
      appearance of the main metabolite of coumarin administered orally but increases
      its recovery. Due to scopoletin formed from the grapefruit juice, experiments
      especially with coumarin are strongly affected.

PMID- 8737763
TI  - Effect of food on the bioavailability of oxybutynin from a controlled release
      tablet.
AB  - OBJECTIVE: The effect of food on the bioavailability of oxybutynin was assessed
      in a randomised cross-over study in 23 healthy volunteers. A single oral 10 mg
      dose of a controlled release oxybutynin tablet was administered after a high fat
      breakfast and to fasting subjects. The AUC, Cmax, tmax, t1/2 and MRT of
      oxybutynin and its active metabolite N-desethyloxybutynin were determined.
      RESULTS: Breakfast did not change the AUC of oxybutynin but increased the AUC of
      N-desethyloxybutynin by about 20%. The Cmax of oxybutynin and N
      desethyloxybutynin were two-fold higher when the drug was administered after
      breakfast compared to the fasting state. CONCLUSION: Breakfast significantly
      reduced the MRT of oxybutynin and N-desethyloxybutynin.

PMID- 8737765
TI  - Influence of repeated oral doses of ethinyloestradiol on the metabolic
      disposition of [13C2]-ethinyloestradiol in young women.
AB  - OBJECTIVE: To examine the influence of daily oral administration of
      ethinyloestradiol on the total clearance of 13C-labeled ethinyloestradiol in
      women. METHODS: 19, healthy, young women received a single IV dose of 0.06 mg 13C
      ethinyloestradiol. Subsequently, they were treated with daily oral doses of 0.06
      mg ethinyloestradiol for 8 days. On the last day of oral treatment, they received
      a further IV dose of 0.06 mg 13C-ethinyloestradiol. The pharmacokinetic
      parameters clearance, area under the serum level-time curve, terminal half-life,
      steady-state volume of distribution and mean residence time of 13C
      ethinyloestradiol in each volunteer were evaluated after both IV doses, and the
      corresponding pairs of parameters were examined statistically for the
      significance of intraindividual differences. RESULTS: Following the first
      (second) intravenous administration, the mean area under the curve was 2.54
      (2.67) ng.h.ml-1. The terminal half-life and mean residence time were 9.7 (9.6) h
      and 10.5 (10.1) h, respectively. The steady-state volume of distribution was 4.3
      (3.9) 1.kg-1 and the clearance was 7.0 (6.6) ml.min-1.kg-1. No significant
      difference was observed in any of these parameters between the first and the
      second IV doses of 13C-EE2. CONCLUSIONS: Since the clearance in particular
      remained unchanged after repeated oral administration of ethinyloetradiol, the
      hypothesis that ethinyloestradiol can inhibit its own metabolism in vivo can be
      rejected.

PMID- 8737766
TI  - Effect of physical activity on serum concentrations of digoxin and digitoxin.
AB  - OBJECTIVE: To study the influence of moderate physical activity on serum
      concentrations of digoxin, digitoxin and albumin. METHODS: Blood samples were
      drawn from 10 consecutive mobile patients on digoxin and 12 patients on digitoxin
      therapy before and following a 10-min walking period. Digitalis serum
      concentrations were determined by radioimmunoassay, and albumin serum
      concentrations by laser nephelometry. RESULTS: Following physical activity,
      digoxin serum concentrations dropped immediately to 79% of baseline values and
      remained significantly decreased for 20 min. Digitoxin concentrations did not
      change significantly. CONCLUSION: In contrast to digoxin, the effect of physical
      activity the serum concentration of digitoxin can be disregarded.

PMID- 8737767
TI  - Stereoselective pharmacokinetics of mefloquine in young children.
AB  - OBJECTIVE: the stereospecificity of mefloquine pharmacokinetics in children has
      been investigated. PATIENTS: Twelve children aged 6 to 24 months were treated for
      uncomplicated falciparum malaria with a single oral dose of 25 mg.kg-1 racemic
      mefloquine in combination with sulfadoxine and pyrimethamine. METHODS:
      concentrations of mefloquine enantiomers were determined using a coupled achiral
      chiral chromatographic system. Pharmacokinetic parameters were calculated using
      model-independent analysis. RESULTS: Maximum plasma concentrations, areas under
      the curve and apparent plasma elimination half-lives were higher for the (-)
      enantiomer than its antipode. In contrast, the apparent volume of distribution
      (V/f) and total clearance (Cl/f) values were higher for the (+) enantiomer.
      CONCLUSION: the stereoselectivity of mefloquine pharmacokinetics is similar to
      that observed in adults.

PMID- 8737768
TI  - Concept of bridging studies and ethical concerns.

PMID- 8737769
TI  - Experimental and clinical results of fiberoptic argon laser stapedotomy.
AB  - Since 1992 a small air-cooled opthalmological argon laser (Argus system, 3 W
      max.) equipped with a fiberoptic microhandpiece has been used for stapedotomy at
      the Inselspital, Berne. The microhandpiece has been developed especially for
      otological purposes in our electronic laboratory. In order to measure the effect
      of argon laser pulses applied through the handpiece to the ear, we performed
      temperature measurements in a saline-filled inner ear model by using ultrathin (2
      microns thick), ultrafast (4 ns) thermosensitive rhodamine-coated polyurethane
      films. Multiple laser pulses of 1-2.5 W and 0.1 s duration - as used in clinical
      applications - produced a temperature elevation of about 1 degree C in the liquid
      of the inner ear model. The local laser effect was then examined histologically
      on the isolated stapes. The thermal damage zone around the stapedotomy
      perforation was limited to about 100 microns. In a clinical study we compared the
      results of argon laser stapedotomy (n = 54) with those of a skeeter microdrill
      stapedotomy (n = 29). Substantial hearing gains were found in all cases in both
      groups. In the laser stapedotomy group the mean residual air-bone gap (0.5-2 kHz)
      was 10 dB or less in all cases but one. Inner ear function remained unchanged
      except for a 40-dB loss at 4000 Hz in one case. Transient vertigo with nystagmus
      occurred in one case. Facial nerve dysfunction did not occur in any patient. The
      most important advantage of the laser found was the absence of mechanical trauma
      to the stapes. Stapes luxation and a floating footplate were avoided. In
      contrast, thick footplates were more easily perforated with the skeeter. Use of
      an argon laser equipped with a fiberoptic microhandpiece and a skeeter microdrill
      as needed seems particularly advantageous for stapedotomy.

PMID- 8737770
TI  - In situ real-time sequential potentiometric determinations of potassium
      concentrations from three cochlear regions in noise-exposed rats.
AB  - Double-barrelled potassium selective microelectrodes (K-ISME) were used in situ
      for real-time sequential determinations of potassium concentrations (CK+) in
      endolymph, marginal cells and the spiral ligaments of rats exposed to moderate
      noise at 100 dB for 30 min (NE) and control (CTL) animals. CK+ in NE animals at
      these sites did not differ significantly when compared to CK+ in CTL animals.
      However, there was a slight decrease in CK+ in marginal cells in the noise
      exposed animals.

PMID- 8737771
TI  - A comparison of morphological effects on the rabbit nasal and sinus mucosa after
      surgical denervation and topical capsaicin application.
AB  - In order to study morphological effects on the nasal and sinus mucosa, New
      Zealand White rabbits underwent either unselective, regional sectioning of
      sensory and parasympathetic nerve branches or topical treatment of the mucosa
      with capsaicin. Ten days after treatment, mucosal specimens were analyzed by
      light and electron microscopy. Immunohistochemistry was used to evaluate
      neuropeptides present, in particular substance P, calcitonin gene-related
      peptide, vasoactive intestinal peptide and neuropeptide Y. In surgically
      denervated rabbits, mucosal glands were found to be enlarged and contained an
      increased number of zymogen granules having a bipartite substructure. Topical
      capsaicin application caused localized epithelial changes in the sinus mucosa and
      maxilloturbinal region of the nose, including clotting of cilia and an increased
      number of goblet cells. Reduced amounts of all neuropeptides investigated were
      found in the surgically denervated animals, while topical capsaicin treatment had
      only marginal effects on the mucosal neuropeptide content. The morphological
      changes observed after surgical denervation suggest an imbalance between neural
      stimulation and secretory capacity of the mucosal glands. These findings could
      explain the difference in clinical effect noted between sectioning of the vidian
      nerve and topical treatment with capsaicin in patients with perennial rhinitis.

PMID- 8737772
TI  - Morphological changes in rat submandibular gland mucous cells during fixation
      with 10% formalin.
AB  - The features of mucous cells in 10% formalin (FA)-fixed submandibular glands
      differ markedly from those fixed in glutaraldehyde (GA). We therefore studied
      morphological changes in mucous cells during 10% FA fixation. Mucous cells were
      fixed in either 10% FA, neutral sodium-phosphate-buffered (Na-PBed) 10% FA, ice
      cold 10% FA or an ice-cold fixative mixture of 2.0% paraformaldehyde (PA) and
      0.5% GA. Two different methods were used: immersion fixation and venous perfusion
      fixation. The 10% FA-fixed tissues had elliptical or flattened nuclei, a clear
      cytoplasm and no secretory granules. Tissues fixed with the fixative mixture
      displayed almost round nuclei, a broad endoplasmic reticulum and abundant
      secretory granules in the cytoplasm. Tissues immersion-fixed with neutral Na-PBed
      10% FA or perfusion-fixed with ice-cold 10% FA had almost the same light
      microscopic appearance as that of the mixture-fixed tissues. To elucidate the
      process of morphological changes during 10% FA fixation at room temperature,
      samples immersed in 10% FA for varying periods of time were postfixed immediately
      in the fixative mixture and exposed to microwave irradiation. This method
      produced a variety of findings, even within the same section. There was a
      significant difference in the findings seen in the center of the section and at
      the periphery. The initial changes caused by 10% FA were rupture of the secretory
      granules located in the perinuclear region and destruction of the perinuclear
      organelles such as Golgi apparatus, mitochondria and endoplasmic reticulum.
      Absorption of the endoplasmic reticulum progressed so that the perinuclear region
      became translucent. To obtain a better structure in mucous cells from the fixed
      submandibular gland tissues, an appropriate fixative such as GA should be used
      and the fixative should infiltrate into the tissues as quickly as possible.

PMID- 8737773
TI  - Middle-latency responses to assess objective thresholds in patients with noise
      induced hearing losses and Meniere's disease.
AB  - In this study 23 patients with noise-induced hearing loss (NIHL) referred for
      medico-legal evaluation and a group of 18 cases with Meniere's disease were
      evaluated audiologically using the middle-latency response (MLR). Cross
      correlation functions were used to assess precisely MLR thresholds in low and
      middle frequencies. Cross-correlation data obtained from suprathreshold levels to
      below threshold levels were compared with the normal limits of parameters found
      at threshold levels, allowing us to determine the true MLR threshold. Our results
      revealed that this MLR threshold and visual detection thresholds were different
      in 18% of both the NIHL and Meniere's disease groups. In this population the true
      MLR threshold was greater by 5 dB. These findings demonstrated that cross
      correlation functions can enhance the sensitivity of the definition of the MLR
      threshold. True MLR thresholds were compared with subjective pure-tone
      audiometric (PTA) thresholds at the same frequencies (0.5, 1 and 2 kHz). The true
      MLR threshold and PTA threshold were in agreement within 10 dB in 91% of the NIHL
      group and all of the Meniere's disease group. The PTA threshold was greater by 15
      dB or more in the remaining NIHL group. If a criterion of 15 dB discrepancy
      indicates non-organic hearing loss, it can be inferred that 9% of an NIHL
      population referred for medico-legal evaluation is exaggerating subjective
      audiometric thresholds.

PMID- 8737775
TI  - A comparison of topical Emla cream with Bonain's solution for anesthesia of the
      tympanic membrane during tympanocentesis.
AB  - The purpose of this study was to investigate the relative efficacy of Emla cream
      (a eutectic formulation of lignocaine and prilocaine) and Bonain's solution
      (equal amounts of cocaine hydrochloride, menthol and phenol) as local anesthetic
      agents to the tympanic membrane. Fifty patients undergoing bilateral
      tympanocentesis were included. The patients were used as their own controls. One
      tympanic membrane was anesthetized with Emla cream and the other with Bonain's
      solution. The operating microscope was used. After a 30 min analgesic time,
      tympanocentesis was performed with aspiration of middle ear secretions. Each
      patient was then asked to fill in a questionnaire that graded the severity of
      pain experienced: none, very mild, mild, moderate or severe. Findings showed that
      Bonain's solution was more effective in tympanocentesis. All patients experienced
      no pain to very mild pain. With Emla cream 15 of 50 patients experienced mild to
      moderate pain. No significant side effects occurred with either anesthetic agent.

PMID- 8737776
TI  - Pre- and postoperative evaluation of patients with nasal obstruction undergoing
      endoscopic sinus surgery.
AB  - Functional endoscopic endonasal sinus surgery (FESS) is at present the surgical
      method of choice for many clinicians treating chronic sinusitis and nasal
      polyposis. Postoperatively, patients have felt that patency of the nasal airway
      is improved, although all previous studies have failed to objectively measure
      changes produced. By using anterior active rhinomanometry, decreased unilateral
      and total nasal resistance was measured. Although improvement in total resistance
      was not statistically significant, reduction in unilateral resistance was. All
      patients demonstrated subjective improvements in unilateral and total nasal
      patencies. The reduction in nasal resistance was more pronounced in baseline
      resistance values than after decongestion, indicating that FESS had a positive
      effect on mucosal edema but did not alter the structural anatomy of the main
      nasal passages.

PMID- 8737774
TI  - Cytokeratin 18 expression in squamous cell carcinoma of the head and neck.
AB  - Cytokeratin (CK) expression was studied in squamous cell carcinomas of different
      subsites in the head and neck by using cryostat sections from 27 head and neck
      squamous cell carcinomas (HNSCCs) and 6 cell lines established from HNSCC. All
      tissues were analyzed immunohistochemically with a panel of monospecific anti
      keratin monoclonal antibodies. Most carcinomas recapitulated the expression
      pattern of keratins present in the basal layer of normal epithelium from the site
      of tumor origin. Regional differences in the expression of simple-epithelial type
      of keratins in stratified (pseudostratified) epithelia were to a large extent
      repeated in corresponding carcinomas. In the present study, localization of
      various keratins were surveyed and CK 18 specific monoclonal antibodies were
      specifically used to distinguish SCCs of the larynx or hypopharynx from SCCs of
      the oral cavity. CK 18 staining of almost all tumor cells was detected in 11 of
      12 SCCs of the larynx and hypopharynx, but was only detected sporadically in 3 of
      9 SCCs of the oral cavity. The present results show that CK 18 typing might be
      useful for distinguishing sites of origin of various HNSCCs. Findings also
      indicate that CK 18 expression in SCC might be modulated by microenvironmental
      factors.

PMID- 8737777
TI  - A comparative study of psychological aspects of recurring and non-recurring
      functional aphonias.
AB  - The present study is based on the hypothesis that patients with recurrent attacks
      of aphonia differ from those with non-recurring attacks of aphonia in their
      anxiety levels, social assertiveness and stress-coping strategies. A comparison
      was made between 21 women with recurring aphonia and 19 women with non-recurring
      aphonia with respect to these three factors. Seventeen healthy women served as
      volunteers. Compared to patients with non-recurring aphonias, patients with
      recurring aphonias exhibited a significantly higher level of anxiety and
      significantly more respect for social norms and codes of propriety. Their coping
      was also characterized by a higher escape tendency. Patients with recurring
      aphonias also reported a significantly higher number of problems in their private
      lives within the preceding 5-year period. In therapy patients should be
      encouraged to reflect upon a possible rigidity toward social norms and better
      understand fears regarding conflicts in personal relationships.

PMID- 8737778
TI  - Human keratinocyte culture from the peritonsillar mucosa.
AB  - Tonsillectomy tissue can be used as a routine source for cultures of
      oropharyngeal keratinocytes. In so doing, a peritonsillar strip of unaltered
      mucosa was dissected in the upper submucosa. Subsequent trypsinization yielded
      7.0 +/- 3.4 x 10(6) keratinocytes per bilateral tonsillectomy. Keratinocyte
      attachment and growth in primary culture were promoted by sublethally irradiated
      3T3 murine fibroblasts. Three subcultures could be performed without a feeder
      layer and were characterized by a population doubling time of 4.5 days during log
      growth phase. Electrophoretic and immunoblot analysis of the third subculture
      revealed a strong expression of keratin pairs 5/14 and 6/16 as well as keratins 7
      and 19, whereas keratins 8/18 were expressed less intensely. The lowest
      intensity, was found for keratin 13, which is known to be indicative of the
      differentiated mucosa. The culture technique thus provides an easily available in
      vitro model for morphological and functional studies on the epithelial
      compartment of human oropharyngeal mucosa.

PMID- 8737779
TI  - Interleukin 1 (IL-1) and IL-1-receptor antagonist (IL-1-RA) in middle ear
      cholesteatoma: an analysis of protein production and biological activity.
AB  - Cytokine networks are now presumed to play an essential role in the pathogenesis
      of middle ear cholesteatoma. Of the factors identified in cholesteatoma,
      interleukin-I (IL-1)-alpha appears to be especially important because of its
      stimulation of keratinocyte proliferation as well induction of bone resorption.
      To further characterize the possible role of IL-1 in the pathogenesis of
      cholesteatoma, we quantified the levels of IL-1 and IL-1-receptor antagonist (IL
      1-RA) present using the bicinchonic acid protein assay and enzyme-linked
      immunosorbent assay (ELISA) on tissue extracts from 20 cholesteatoma specimens.
      The presence of biologically active IL-1 was also analyzed, using the cell line
      LBRM-33 and an ELISA for the detection of interleukin-2 (IL-2). Human skin
      obtained from the external ear canal was used as control. The amounts of IL-1
      alpha in cholesteatoma (34.9 +/- 19.5) were higher than in human skin (6.7 +/-
      2.8). The observed differences were statistically significant by Student's t-test
      (P < 0.01). Skin samples showed elevated concentrations of IL-1-RA (248.3 +/-
      30.2) in comparison to that in the cholesteatoma (80.8 +/- 13.5). This was also
      statistically significant (P < 0.01). Whereas IL-1 activity was not detected in
      skin samples, all cholesteatoma specimens studied showed a stimulation effect on
      the production of IL-2 when incubated with the cell line LBRM-33. The results
      point to an over-expression of IL-1 concurrent with a decreased secretion of IL-1
      RA in middle ear cholesteatoma. Furthermore IL-1-RA production is deficient
      relative to total IL-1 production, resulting in the presence of active IL-1.

PMID- 8737780
TI  - The association of cancers of the larynx with cancers of the lung.
AB  - We report 77 cases of associated primary cancers of the larynx and lung that were
      managed at the Department of Otolaryngology, University of Padua, between 1980
      and 1994. To our knowledge, this is the largest series reported in the literature
      to date. This association is not a chance finding, but presumably the result of
      common pathogenetic factors.

PMID- 8737781
TI  - The nasopharyngeal bacterial flora in children with otitis media with effusion.
AB  - A study was undertaken to evaluate the incidence of nasopharyngeal alpha
      streptococci with inhibitory activity against pathogens, as a defense mechanism
      of the normal bacterial flora against infection. Cultures were taken from the
      nasopharynges of 43 children with otitis media with effusion (OME). The detection
      rates of alpha-streptococci with inhibitory activity against Haemophilus
      influenzae, Streptococcus pneumoniae, Staphylococus aureus and group A
      streptococci were significantly lower in the nasopharynx than those isolated from
      the tonsils of the same patients. Moreover, the detection rates of alpha
      streptococci with inhibitory activity against all of these pathogens derived from
      the nasopharynx were lower than those in healthy children, streptococcal strains
      with activity against H. influenzae and Strep, pneumoniae were also lower than
      that in patients with tonsillitis. These findings suggest that low nasopharyngeal
      levels of alpha-streptococci with inhibitory activity against respiratory
      pathogens may render children susceptible to OME. Further studies are needed to
      investigate the relationships between the prevalence of pathogens in the
      nasopharynx and the inhibitory activities of alpha-streptococci against them in
      order to devise and select optimal treatment for patients with OME.

PMID- 8737782
TI  - Detection of viral antigen in the endolymphatic sac.
AB  - A study was devised to determine whether or not any immune defense mechanism is
      present when a virus invades the human endolymphatic sac (ES). The ES was removed
      from 14 fresh autopsy cases having no known pre-mortem diseases in the middle and
      inner ears. Specimens were then examined for viral antigens including herpes
      simplex (HSV) type 1 and 2, mumps and cytomegalovirus using immunohistochemical
      methods. DNA examination by in situ hybridization was also performed for HSV. HSV
      antigen and DNA were observed in 9 of the 14 cases studied. These findings
      suggest that the virus invades the ES but is impeded by an immune defense
      mechanism under normal conditions. Since disease may alter host defenses, further
      studies are warranted to study the relationship between HSV and patients with
      Meniere's disease.

PMID- 8737783
TI  - The relationship between orthostatic dysregulation and the orthostatic test in
      dizzy patients.
AB  - The orthostatic test was administered to 134 dizzy patients (37 males and 97
      females) who were identified as having orthostatic dysregulation from December
      1990 through November 1994. The mean age of the male and female patients was 42.5
      and 44.6 years, respectively, and the peak age decade was the 50s. Among the
      questionnaire items for orthostatic dysregulation, orthostatic dizziness was the
      most frequent major symptom and occurred in 116 of the patients (86.6%). Fatigue
      was the most frequent minor symptom and was found in 97 (72.4%). The incidence of
      positive orthostatic test results in the patients with orthostatic dysregulation
      (50.7%) was significantly higher (P < 0.01) than that in the control subjects
      (27.8%). There was also a significant difference (P < 0.01 or P < 0.05) between
      systolic pressure decrease during the orthostatic test procedure in the patients
      with orthostatic dysregulation and that in the control subjects. These results
      suggest that autonomic imbalance as reflected by the orthostatic dysregulation
      questionnaire and orthostatic test results is closely related to the occurrence
      of dizziness or vertigo.

PMID- 8737784
TI  - Immunohistochemical localization of manganese superoxide dismutase in the rat
      cochlea.
AB  - There has been recent increasing interest in the involvement of superoxide
      radicals (O2-) and their scavenging enzymes, the superoxide dismutases, in the
      patho-physiology of certain diseases. Since mitochondria are significant
      intracellular sources of O2- and important targets of oxidant injury, determining
      the intracochlear localization of mitochondrial O2- scavenging enzyme may provide
      important insight into the pathogenesis of injury due to cochlear oxidants. In
      order to locate the mitochondrial O2- scavenging enzyme, manganese superoxide
      dismutase (MnSOD), the authors used a modified immunoglobulin peroxidase bridge
      sequence method to detect MnSOD in paraffin-embedded, formalin-fixed rat
      cochleas. Site-specific immunolocalization of MnSOD could be demonstrated in the
      cochlear labyrinth, suggesting that the generation of intracochlear O2- was
      possibly implicated in the metabolically active sites and sites rich in
      vascularity. This study also provided a useful probe for detecting MnSOD
      immunohistochemically from ethylenediamine tetra-acetic acid-treated materials
      without requiring an antigen retrieval procedure.

PMID- 8737785
TI  - Application of the ATP-bioluminescence assay to thermosensitivity testing for
      head and neck cancer.
AB  - We investigated the usefulness of the ATP assay as a thermosensitivity test in
      comparison with a colony-forming assay (CFA). The intracellular ATP levels in KB
      cells were markedly decreased after exposure to hyperthermia (43 degrees C for 1
      h), reaching less than half that in the control cells in 12-18 h, and recovering
      gradually thereafter. The effect of hyperthermia assessed by the ATP assay
      closely correlated to that assessed by CFA, not only when KB cells were heated at
      42, 43, and 44 degrees C but also in the conditions where L, KB and IMC-3 cell
      lines were heated at 43 degrees C. Findings showed that the ATP assay can be
      performed easily and more quickly than CFA for evaluating cell viability after
      heating. We also investigated heterogeneous responses to hyperthermia in cells
      from fresh surgical specimens of tumors. Thus, this rapid and reliable test was
      found to be useful for predicting the outcome of hyperthermia as a clinical
      treatment.

PMID- 8737786
TI  - Allograft stapes surgery for conductive hearing loss in patients with ossicular
      chain anomalies.
AB  - An allograft stapes was used during surgical intervention for conductive hearing
      loss due to ossicular malformations in 11 ears of seven patients. The external
      auditory canal and tympanic membrane were normal in all ears. The surgical
      findings for the ossicles were stapes fixation (7 ears), stapes fixation with
      discontinuity of the incudostapedial joint (in both ears of one patient), a
      deformed incus and stapes crura compressed by the facial nerve (one ear in which
      the stapes was not fixed) and an anomaly of the incus and stapes combined with a
      dermoid cyst (in one ear in which the stapes was also not fixed). In all ears,
      the following procedures were performed: stapedectomy followed by sealing the
      oval window with a vein graft and placing an allograft stapes between the oval
      window and the lenticular process of the incus or the handle of the malleus. The
      allograft stapes was placed with its capitulum on the oval window in all cases,
      and fibrin glue was used for stabilizing the seal and the allograft stapes. The
      indications for stapedectomy for conductive hearing loss due to ossicular chain
      anomalies and the utility of allograft stapes are discussed.

PMID- 8737787
TI  - Neuroendocrine cells in the cat laryngeal epithelium.
AB  - The structure and distribution of neuroendocrine cells in the feline laryngeal
      epithelium were examined using immunohistochemical techniques. Neuroendocrine
      cells were often spindle shaped, with cytoplasmic processes directed towards the
      lumen and basement membrane. The apical portion of the cells usually reached the
      laryngeal lumen with microvillous projections. The cytoplasm always contained
      variable numbers of electrondense cored vesicles. The number of neuroendocrine
      cells decreased in the following order: subglottis, posterior glottis,
      supraglottis, anterior glottis. Neuroendocrine cells contained calcitonin gene
      related peptide, substance P and/or 5-hydroxytryptamine. They also showed protein
      gene product 9.5 or neuron-specific enolase immunoreactivity. These observations
      suggest that neuroendocrine cells play a part in the regulatory function of the
      cat larynx by releasing various peptides. These substances may contribute to
      allergic reactions or control mucus secretion by acting via the endocrine or
      paracrine pathways and/or neurosecretory pathways.

PMID- 8737788
TI  - Management of war-related neck injuries during the war in Croatia, 1991-1992.
AB  - From 1 September 1991 to 31 December 1992, a total of 7,043 wounded patients were
      treated in the War Hospital in Slavonski Brod. Seven hundred and twenty eight
      patients with head and neck injuries were treated in the Department of
      Otorhinolaryngology and Cervicofacial Surgery. Of this number, 187 had neck
      injuries. Ninety-two (49.2%) of them were treated in outpatient facilities and 95
      (50.8%) as inpatients. Immediate exploration was done in 84 patients with
      penetrating neck injuries. Vital structures were involved in 49 patients: major
      blood vessels (40 cases), larynx (17 cases), pharynx (8 cases), trachea (5
      cases), thyroid gland (3 cases) and esophagus (2 cases). Definitive treatment was
      given to all of these injuries. Primary wound closure was performed upon
      exploration in 74 patients who were treated within the first 6 h after trauma.
      Secondary wound closure was performed in 10 patients with neck exploration
      performed more than 6 h after injury, and in those with extensive defects of
      tissue requiring the use of larger local flaps or free flaps. The mortality among
      patients with neck injuries was 2.1%.

PMID- 8737789
TI  - Herpes simplex virus type I reactivation as a cause of a unilateral temporary
      paralysis of the vagus nerve.
AB  - Infection by neurotropic viruses, as exemplified by the herpes family, is
      universally accepted as a cause of palsies of the cochleo-vestibular and facial
      nerve. Palsies of the vagus nerve with a possible viral etiology have been
      described, although viruses have been identified in only a few selected cases. We
      report a 52-year-old man with unilateral otalgia, hoarseness and dysphagia.
      Examination revealed unilateral (left-sided) pharyngeal dysfunction, and
      paralysis of the left vocal cord fixed in the paramedian position. A barium
      swallow documented dysfunction of the left pharyngeal constrictor muscles. These
      findings suggested the lesion to be located either at the inferior ganglion of
      the vagus nerve or cranially. At direct laryngoscopy a smear was obtained from a
      4-mm mucosal ulcer at the region of the left arytenoid cartilage. This smear
      demonstrated antibodies to herpes simplex virus (HSV) type I by
      immunofluorescence. On follow-up 19 months after the initial infection there was
      complete remission of the paralysis of the left vocal cord and normal pharyngeal
      function. The demonstration of HSV type 1 antibodies from a mucosal lesion in the
      distribution of the superior laryngeal nerve suggests that reactivation of HSV
      type I was the most likely explanation for the temporary nerve palsy seen.

PMID- 8737790
TI  - The LAURA multichannel cochlear implant in a true Mondini dysplasia.
AB  - A congenitally deaf child with bilateral Mondini dysplasias of the inner ear was
      successfully implanted with a LAURA multichannel cochlear prosthesis. This is the
      first report of a patient with a Mondini dysplasia in whom a LAURA multichannel
      cochlear prosthesis was successfully implanted. The cerebrospinal fluid leakage
      typically occurring after cochleostomy in similar patients was readily
      controlled, indicating that the deformity present was not a contra-indication for
      cochlear surgery. The audiological results obtained are described in detail.
      Since the internal unit of the LAURA prosthesis is very flexible, various speech
      processing strategies, such as continuous interleaved and phase-locked continuous
      interleaved strategies, can be tried and evaluated.

PMID- 8737791
TI  - Bilateral acoustic neurofibromatosis with bilateral multicentric facial
      schwannomas.
AB  - A case report of a 20-year-old female with bilateral acoustic neurofibromatosis
      (NF-2) and bilateral facial schwannomas is presented. Multiple segmental
      schwannomas were found with clinically intact tissue between each tumoral
      enlargement in the right parotid region. Translocation (2;8) (p2.4:q2.1) was
      detected in this patient, and has not been reported in a schwannoma until now.
      The patient's family would not allow any major surgery to be performed.

PMID- 8737792
TI  - Do laws of biomechanics work in reconstruction of the cartilaginous nasal septum?
AB  - "Biomechanical" techniques can be used for correcting C-shaped or S-shaped nasal
      septum cartilage deformities. These include mucoperichondrium elevation on the
      concave side, trimming cartilage to its necessary size, incisions to release
      cartilaginous bends and strip resections. Resection and reimplantation of
      cartilage are preferable when correcting a difficult post-traumatic septum. While
      biomechanical principles are applicable to nasal septum surgery, further clinical
      studies must be devised to provide proper correction of the nasal septum with
      minimal sacrifice of cartilage.

PMID- 8737793
TI  - Repair of the ossicular chain with an ionomer cement by an inadequate incus after
      prior stapes surgery for otosclerosis.
AB  - Use of an ionomer bone cement is described for repairing the ossicular middle ear
      system in revision stapes surgery. The cement was used to enlarge an eroded
      inadequate incus to allow placement of a new stapes prosthesis. Reconstruction of
      the incus with this new bone cement was readily performed and hearing results
      after 2 years of follow-up have been promising.

PMID- 8737794
TI  - The role of different imaging procedures in early diagnosis and management of
      descending necrotizing mediastinitis.

PMID- 8737795
TI  - Brain stem dermoid cyst.

PMID- 8737796
TI  - Toward a departmental view of developmental neurosciences.

PMID- 8737797
TI  - Cerebrospinal shunt infections in infants.

PMID- 8737798
TI  - The significance of an international society.

PMID- 8737799
TI  - Neurovascular developmental interaction: a specific form of vascular
      maldevelopment in the malformed brain. I. An experimental study and proposal of a
      new teratological concept.
AB  - The process of the development of the intracranial vessels was studied by means
      of immunohistochemical analysis of factor VIII in normal and exencephalic chick
      fetuses. The results revealed that the development of blood vessels in
      exencephalic brain was far advanced beyond the norm, with intense
      immunoreactivity to factor VIII on postincubation day 16 exceeding that on day 21
      in normal controls. Compared with results regarding the direction of the
      overgrowth in the neuronal maturation process in the previous study using the
      chick exencephaly model, the findings of overmatured blood vessels were
      compatible with NSE- and somatostatin-positive elements that appeared especially
      in the overgrowth foci. The results of the present study suggested the pathogenic
      development of the "area cerebrovasculosa" in the neural placode as a phenomenon
      consequent upon hypervascularization in response to neuronal overgrowth, as seen
      in human cases of exencephaly or anencephaly. We emphasize the significance of
      this specific phenomenon in the development of the fetal central nervous system,
      namely neurovascular developmental interaction.

PMID- 8737800
TI  - Complications of endoscopic neurosurgery.
AB  - Neuroendoscopy is rapidly becoming an essential part of the neurosurgeon's
      repertoire. Currently, very few studies have identified the complications of this
      new technique, yet many have warned of the steep learning curve associated with
      its practice. We have reviewed the last 173 neuroendoscopic procedures performed
      by one surgeon and identified two distinct groups of complications: those that
      have clinically significant sequelae and those that cause concern
      intraoperatively but no overt clinical problems. The 173 procedures were
      performed on 152 patients. Of these patients, 11 suffered significant
      complications (7%). Twenty-two of the procedures were complicated by
      intraoperative problems (13%). The incidence of insignificant complications
      appeared to decrease with experience, whereas that of the significant ones did
      not. These complications occurred in association with a wide variety of
      operations over a 2-year period. We conclude that neuroendoscopy is a relatively
      safe technique with an overall 7% complication rate and a steep learning curve,
      and that, with a few simple guidelines, it can be employed by all neurosurgeons
      for the betterment of their patients.

PMID- 8737801
TI  - Early-onset progressive encephalopathy with migrant, continuous myoclonus.
AB  - Three unusual cases of focal continuous myoclonus with onset during the first
      months of life, lasting from dozens of minutes to hours, are reported. During
      disease evolution, prolonged bilateral myoclonic seizures and generalized tonic
      clonic seizures occur. Subsequently, a progressive encephalopathy with hypotonia
      and ataxia appears. A net worsening of the neurological condition is observed
      after the age of 4-5 years. Cortical atrophy is shown by CCT and MRI.
      Neurometabolic screening is not contributory. Repeated polygraphic recordings
      show continuous and segmental myoclonic jerks, localized in different muscles, at
      frequencies ranging between 0.5-1 c/s and 6-8 c/s. Moreover action myoclonus is
      recorded. During the first period of disease the EEG does not show any paroxysmal
      activity. As to the classification, this syndrome corresponds to an early onset
      progressive encephalopathy of unknown origin, similar in some aspects to Alper's
      disease. Another problem is the interpretation of the myoclonic phenomena. Some
      important aspects suggest a cortical origin of the diverse myoclonic phenomena
      observed in these cases.

PMID- 8737802
TI  - Congenital myopathy with type II muscle fiber hypoplasia.
AB  - An unusual congenital neuromuscular disease characterized by atypically small
      type II muscle fibers is reported. The patients were a 9-year-old boy and a 3
      year-old boy, both of whom showed motor retardation with proximal muscle wasting
      and hypotonia. Muscle biopsy revealed hypoplastic type II fibers and normal type
      I fibers. The observed hypoplasia seems to be a primary alteration.

PMID- 8737804
TI  - The place of decompressive surgery in the treatment of uncontrollable post
      traumatic intracranial hypertension in children.
AB  - The authors report two cases of post-traumatic uncontrollable intracranial
      hypertension in children (120 torr in case 1; 90 torr in case 2) who were treated
      within the first 12 h after trauma by surgery including decompressive
      craniectomy. The outcome was favourable in both children. Intracranial pressure
      (ICP) was recorded during the pre-, intra- and postoperative periods and during
      each specific step of the surgical procedure. Craniectomy alone induced a
      decrease in ICP of 45% (40 torr) in case 1 and 30% (35 torr) in case 2. Although
      this method remains controversial, given the lack of controlled trials, it can
      offer a salvage procedure in children with rapidly worsening intracranial
      hypertension, allowing survival without disabling neurological sequelae.

PMID- 8737803
TI  - High-dose radiation-induced meningiomas following acute lymphoblastic leukemia in
      children.
AB  - The authors review three personal cases of patients who developed cerebral
      meningiomas following high-dose radiotherapy for acute lymphoblastic leukemia.
      Two patients were female and one male. Their ages when the leukemia appeared were
      between 11 and 15 years. All patients were treated with a course of prophylactic
      irradiation to the neuraxis for a total dose of 24 Gy. After an average interval
      of 10.4 years, all three patients presented a meningioma; histologically, one was
      meningothelial and two were fibrous. All three meningiomas presented atypical
      features. At follow-up 1, 4, and 4 years respectively after surgery, none of
      these patients presents neurological deficits or neuroradiological signs of
      recurrence. Forty-nine cases of high-dose radiation-induced meningioma are also
      reviewed.

PMID- 8737805
TI  - Cranial disjunction and visual failure in a slit ventricle syndrome with patent
      shunt.
AB  - A 6.5-year-old child who received a shunt at 3 weeks of age for triventricular
      hydrocephalus related to his congenital toxoplasmosis developed symptoms of
      intracranial hypertension and papilloedema. Computed tomographic scan
      demonstrated slit ventricles. The shunt device was shown to be patent on isotope
      transit study. Spontaneously the cranial sutures widened and headaches
      disappeared, but loss of vision occurred and did not reverse despite optic nerve
      sheath fenestration. We suspect that a rapid drop in intracranial pressure played
      a role in the pathogenesis of our patient's blindness. This possible complication
      should be taken into account when calvarial expansion is planned in a patient
      with an intracranial hypertension syndrome with papilloedema in the presence of
      slit ventricles and a patent shunt.

PMID- 8737806
TI  - A case of cranial meningocele associated with Joubert syndrome.
AB  - Joubert syndrome was first reported in 1969 as a rare, recessive autosomal
      syndrome associated with neuropathological abnormalities of the cerebellum and
      brain stem, partial or complete aplasia of the cerebellar vermis, and presenting
      with episodic hyperpnea and apnea, oculomotor abnormalities, and psychomotor
      retardation. Having experienced one case of this syndrome with associated cranial
      meningocele, we report the clinical course, MRI features, and surgical findings,
      and discuss the relevant literature.

PMID- 8737807
TI  - Trigeminal neurinomas in infants: report of two cases.
AB  - Two cases of trigeminal neurinoma in two infant girls aged 3 and 6 months are
      reported. Both presented with temporal cranial vault bulging at birth. The 6
      month-old patient suffered onset of focal fits 1 month before admission and her
      neurological examination revealed no abnormalities. The 3-month-old patient had
      right exophthalmus and a subcutaneous fronto-orbital plexiform neurofibroma at
      birth. Neurological examination disclosed a sensory deficit of the first
      trigeminal nerve division. She also had a family medical history of von Reckling
      hausen's disease. The incidence of trigeminal neurinomas in children is reviewed.
      The patients in these two cases are the youngest recorded; the cases are the only
      ones reported in infants. Clinical, radiological, and therapeutic aspects are
      discussed.

PMID- 8737810
TI  - The axonal projections of the Hofmann nuclei in the spinal cord of the late stage
      chicken embryo.
AB  - The projection pattern of the neurons of the paragriseal Hofmann nuclei was
      mapped in the chicken embryo using the lipophilic tracer DiI. This report focuses
      on the pattern of projection from the Hofmann nuclei major observed 1-4 days
      prior to hatching, at which time the projection appears to be substantially
      developed. (1) Each neuron extends a commissural axon through the ventral gray
      matter and across the midline in the ventral commissure. The axons originating
      from a single Hofmann nucleus cross within a stretch of the cord equivalent to
      about one spinal segment. There is a small overlap of the axon populations
      originating from adjacent Hofmann nuclei. After reaching the contralateral
      ventral columns the individual axons bifurcate and extend rostrally and caudally
      up to 5 spinal segments in each direction. The rostral and caudal trajectories
      differ; the rostral axons shift progressively more laterally while the caudal
      axons tend not to deviate from their initial course. (2) Throughout their
      longitudinal course the axons give rise to terminal collaterals that are
      concentrated in lamina 8. Rostrally and caudally the terminals decrease in
      density and become increasingly scattered. (3) Hofmann neurons are multipolar
      with 4-5 laterally directed primary dendrites whose arbors are restricted to the
      Hofmann nucleus major within which the neurons reside. (4) Hofmann neurons
      receive afferent terminals from a longitudinal column of commissural interneurons
      located contralaterally in close approximation to the central canal. Each Hofmann
      nucleus major is innervated by a rostrocaudally restricted subset of these
      presynaptic neurons. The axon trajectories of the presynaptic neurons are similar
      to those of the Hofmann neurons. (5) Paragriseal neurons that are not located
      within Hofmann nuclei major are also commissural intersegmental interneurons and
      tend to be clustered segmentally. The segmentation is clearest for the Hofmann
      nuclei minor, which are clusters of neurons iterated along the ventrolateral
      margin of the thoracic spinal cord but not organized in protruding lobes.

PMID- 8737809
TI  - In vivo inhibition of programmed cell death by local administration of FGF-2 and
      FGF-4 in the interdigital areas of the embryonic chick leg bud.
AB  - The formation of the digits in amniote vertebrates is accompanied by a massive
      degeneration process that accounts for the disappearance of the interdigital
      mesenchyme. The establishment of these areas of interdigital cell death (INZs) is
      concomitant with the flattening of the apical ectodermal ridge (AER), but a
      possible causal relationship between these processes has not been demonstrated.
      Recent studies have shown that the function of the AER can be substituted for by
      implantation of beads bearing either FGF-2 or FGF-4 into the apical mesoderm of
      the early limb bud. According to these observations, if the onset of INZs is
      triggered by the cessation of the AER function, local administration of FGFs to
      the interdigital tissue prior to cell death should delay or inhibit interdigit
      degeneration. In the present study we have confirmed this prediction. Implanting
      Affi-gel blue or heparin beads pre-absorbed with either FGF-2 or FGF-4 into the
      interdigital tissue of the chick leg bud in the stages prior to cell death
      stimulates cell proliferation and causes the formation of webbed digits. Vital
      staining with neutral red confirmed an intense temporal inhibition of
      interdigital cell death after FGF treatment. This inhibition of interdigital cell
      death was not accompanied by modifications in the pattern of expression of Msx-1
      or Msx-2 genes, which in normal development display a domain of expression in the
      interdigital tissue preceding the onset of degeneration.

PMID- 8737808
TI  - Ultrastructure of sympathetic axons and their structural relationship with
      vascular smooth muscle.
AB  - This review focuses on the more recent findings of the structure of sympathetic
      postganglionic axons and the association of their varicose terminals with
      vascular smooth muscle. These studies have investigated the innervation of a wide
      range of vessels from different regions of the vasculature in the rat, guinea pig
      and rabbit and have predominantly used serial sections and computerised three
      dimensional reconstructions of entire varicosities. They have shown, contrary to
      previous studies conducted in the 1960s and 1970s, that sympathetic axon
      varicosities commonly form structurally specialised neuromuscular junctions with
      vascular smooth muscle cells of most resistance arteries and some small veins. In
      addition, they have shown that most axon varicosities innervating small
      arterioles and small mesenteric veins form neuromuscular junctions, indicating
      that neurotransmitter is primarily released at such neuromuscular junctions. This
      review discusses the structure of sympathetic neuromuscular junctions, their
      development, structural diversity and distribution on vessels from different
      regions of the vasculature. These more recent structural findings and their
      possible significance for our understanding of mechanisms involved in neural
      transmission in blood vessels is discussed.

PMID- 8737811
TI  - Development of myocardial fiber organization in the rat heart.
AB  - Confocal laser-scanning microscopy of phalloidine-stained actin fibers is a
      relatively new tool for studying the development of myocardial fiber
      organization. It seems to show orientation of myocytes in rather early embryonic
      stages. To further evaluate the differentiation of the myocardium, this technique
      was compared with transmission electron microscopy in rat embryos aged between 11
      and 18 days. Although the confocal images of actin filament patterns pointed to
      early myocyte orientation, the electron micrographs revealed that even at 17 days
      the ventricular myocardium was far from mature. Myofibrils never completely
      filled the myocytes, and lack of organization was the rule rather than the
      exception. The organized structure as revealed by confocal microscopy was based
      on cell-to-cell continuity, whereas electron microscopy showed crossing and
      disarray within individual myocytes. Exceptions were in the ventricular
      trabeculations, which showed precocious myofiber differentiation. The
      trabeculations probably support ventricular systole in those stages in which the
      free walls do not yet provide efficient contractions. The other exception was the
      wall of the outflow tract, which showed well-oriented myofibrils from early
      stages onwards. Apparently, the outflow tract has a different function in these
      stages. The differences found between confocal microscopy and electron microscopy
      suggest that some caution is indicated in the interpretation of fluorescent
      images of relatively low magnification.

PMID- 8737812
TI  - The ultrastructure of the sensory hairs of the paratympanic organ receptor cells
      in chicken.
AB  - The hair bundle of the receptor cells in the paratympanic organ of the chicken
      was studied by TEM, after fixation in aldehydes/osmium tetroxide or in
      aldehydes/osmium tetroxide/tannic acid. The bundles are formed by a kinocilium
      and by 40-70 stereocilia. The stereocilia are linked to each other by an
      extensive network of filaments. Three types of these connectors are present:
      basal, shaft and apical; the latter consist of side-to-side and tip-to-side
      connectors. We observed that the shaft connectors are well-highlighted only when
      tannic acid was used, while the other connectors are to be found in the
      conventionally fixed specimens also. The tip-to-side connector consists of a
      filament which joins the tip of a stereocilium with the side of an adjacent
      taller stereocilium; we suggest that the distortion of this filament would give
      rise to the mechanosensory transduction. The other connectors probably serve to
      maintain the regular spatial arrangement of the hair bundle and the mechanical
      coupling of the stereocilia. Our study shows that the general conformation of the
      hair bundle and the stereociliary links of the hair cells in the paratympanic
      organ of chicken are similar to those previously described in the hair cells of
      the acoustico lateralis system.

PMID- 8737814
TI  - Formation of the ocular arteries in the chick embryo: observations of corrosion
      casts by scanning electron microscopy.
AB  - An investigation was carried out on the formation of the blood vessels that
      supply the optic cup or eyeball in developing chick embryos ranging in age from
      Hamburger-Hamilton stage 17 (st17) to st44. Corrosion casts of the vasculature
      were made by injecting resin and examined by scanning electron microscopy. The
      optic cup was supplied by branches of the cranial ramus of the circle of Willis
      (CCW) from st17 to st19. By st23, a branch of the CCW and that of the internal
      carotid artery became anlagen of two ophthalmic arteries, namely, the cerebral
      ophthalmic artery (COA) and the internal carotid ophthalmic artery (ICOA)
      respectively. They were continued by primordia of the long posterior ciliary
      arteries, which connected with each other to form a ring around the pupil.
      Between st19 and st26, another branch of the CCW was found, by contrast, to
      supply the primitive pecten. The distal part of the nasal long posterior ciliary
      artery began to atrophy at st28, so the temporal long posterior ciliary artery
      only began to supply the ring artery around the pupil by st30. At the same time,
      the artery supplying the pecten became anastomosed with the ICOA behind the
      eyeball to form the definitive pectinate artery. By st30, the ophthalmic branch
      of the stapedial artery had also formed and connected with the distal part of the
      ICOA behind the eyeball, as well as with the distal part of the COA by st34. The
      supraorbital branch of the stapedial artery, which had replaced the CCW to
      anastomose with the ethmoidal artery by st30, was found to be connected to the
      COA at st36. The main vascular system supplying the eyeball was complete at st36,
      and its structure at st40 and st44 was fundamentally similar to that at st36.

PMID- 8737813
TI  - Distribution of p75 and trk-neurotrophin receptor proteins in adult human
      sympathetic ganglia.
AB  - We investigated the expression of immunoreactivity (IR) for low- (p75) and high
      affinity (trk proteins) neurotrophin-receptor proteins in adult human
      paravertebral-sympathetic ganglion neurons. Mouse monoclonal antibodies against
      the pan-neurotrophin-receptor p75, and rabbit polyclonal antibodies against
      specific epitopes of the intracytoplasmic domain on trk neurotrophin-receptor
      proteins were used in fresh unfixed and formaldehyde-fixed paraffin-embedded
      sympathetic ganglia. All adult human paravertebral-sympathetic neurons displayed
      trkA neurotrophin-receptor-like protein IR, 10% express trkC neurotrophin
      receptor-like protein IR, 37-44% show p75 IR, and no IR was obtained for trkB
      neurotrophin-receptor-like protein. The intensity of immunostaining was
      independent of the neuron size. Labelling of non-neuronal tissues, especially
      blood-vessel walls, was observed for p75, trkA and trkC neurotrophin-receptor
      proteins. These results indicate that overlapping exists in the expression of p75
      and trk neurotrophin-receptor proteins in adult human paravertebral-sympathetic
      neurons, and suggest that neurotrophins might act on these neurons.

PMID- 8737815
TI  - Influence of partial decerebration and hypophyseal allograft on differentiation
      of thymic epithelial cells in chick embryos: an ultrastructural study.
AB  - The thymus of 18-day-old normal-chick embryos, partially decerebrated chick
      embryos, and partially decerebrated embryos bearing hypophyseal allografts were
      analysed by light and transmission electron microscopy. The hypophyseal influence
      on the cytological differentiation of epithelial components has been studied. The
      thymus of partially decerebrated embryos showed a delayed differentiation of some
      types of epithelial cells and a marked decrease in number of lymphoid cells.
      Partially decerebrated embryos with hypophyseal implants showed a consistent
      recovery in the degree of differentiation of epithelial components. These
      findings indicate the influence of the hypophysis in establishing a correct
      environment for stromal cell differentiation.

PMID- 8737816
TI  - The effect of embryonic cerebrospinal fluid pressure and morphogenetic brain
      expansion on wound healing in the midbrain of the chick embryo.
AB  - The role of increased cerebrospinal fluid pressure and morphogenetic brain
      expansion on midbrain wound healing was studied in chick embryos at stages 16-22.
      The embryos were divided into six groups as follows: group I (stages 16/17),
      group II (stages 18/19), group III (stages 20-22), group IV (stages 18/19), group
      V (stages 20-22) and group VI (stages 18/19). The mid-brains of embryos of groups
      I-III were wounded and the embryos re-incubated for varying periods up to 24 h.
      The neuroepithelial wounds of all group-I embryos healed completely within 24 h.
      However, complete healing was observed in only 25% of wounds in group II and
      11.4% in group III by 24 h. To reduce cerebrospinal fluid pressure and thus slow
      down brain expansion, longitudinal wounds (about 0.8 mm long) were made in the
      hindbrain roof plate of group-IV and group-V embryos, and puncture wounds (0.1 mm
      in diameter) also in the hindbrain roof plate of group-VI embryos. This allowed
      cerebrospinal fluid to escape prior to wounding the midbrain. There was a
      significant increase in the proportion of group-IV and group-V embryos with
      completely healed midbrain neuroepithelial wounds (77.3% and 28.6% respectively).
      However, a comparison between groups II and VI embryos yielded no statistically
      significant difference in healing. Thus, increasing cerebrospinal fluid pressure
      and brain expansion adversely affect midbrain neuroepithelial wound healing.

PMID- 8737817
TI  - Ultrastructural localization of NADPH-diaphorase activity in the submucous
      ganglia of the guinea-pig intestine after vagotomy.
AB  - The reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d)
      activity in the axon terminals presynaptic to the submucous neurons of guinea-pig
      intestine following unilateral cervical vagotomy was studied by electron
      microscopy. The reaction product of diaphorase was localized only in the axon
      terminals that contained predominantly small agranular vesicles, and it was
      usually deposited around the vesicles. The terminals that contained predominantly
      large granular or flattened vesicles did not display any signs of diaphorase
      reactivity. Although there were only few diaphorase-positive submucous neurons in
      the small intestine, a considerable number of diaphorase-positive axon terminals
      was observed in the submucous ganglia of the small intestine in the control
      animals. Ten days after vagotomy, the quantitative study showed that when
      compared with the control animals, the number of diaphorase-positive terminals in
      the submucous ganglia of duodenum, mid-small intestine and colon in the
      vagotomized animals was reduced (P < 0.05). When the NADPH-d-positive terminals
      were examined in closer detail, it was found that only a small proportion of them
      showed signs of degeneration as evidenced by the swelling and vacuolation of
      their contents of mitochondria, with disrupted cristae and clumping of synaptic
      vesicles. It was therefore concluded that at least some of the diaphorase
      positive axon terminals in the submucous ganglia of guinea-pig intestine
      originated from the vagus nerve.

PMID- 8737818
TI  - Formation and dynamics of female and male pronuclei in the fertilization of the
      eggs of Rana limnocharis.
AB  - Eggs of Rana limnocharis were inseminated with conspecific sperm and the
      formation and timing of the second polar body, the formation of female and male
      pronuclei, and their dynamic movements were observed. Sperm enter the egg at
      random locations around the second polar body, between 15 degrees and 60 degrees.

PMID- 8737819
TI  - A classification scheme for malformations of cortical development.
AB  - Malformations of the cerebral cortex are being recognized more frequently as a
      cause of epilepsy, developmental delay, neurological deficits, and mental
      retardation. Nonetheless, a standard nomenclature and classification system of
      these malformations, based upon state-of-the art knowledge derived from genetics,
      embryology, imaging, and pathology, has not been devised. In this manuscript, we
      propose such a classification system. Moreover, we have constructed the system
      such that both the framework and the classifications themselves are flexible and
      can be adapted as our knowledge of the embryology, genetics, imaging, and
      pathology of these disorders advances. We believe that the use of this
      classification system will help both clinicians and researchers to understand and
      think about these disorders and their causes better. In turn, we hope that this
      improved understanding will lead to further refinements in classification, to
      advances in our knowledge and, ultimately, to improvements in therapy.

PMID- 8737820
TI  - Localized proton magnetic resonance spectroscopy of cerebral metabolites.

PMID- 8737822
TI  - Brain perfusion SPECT in infantile neuronal ceroid-lipofuscinosis (INCL).
      Comparison with clinical manifestations and MRI findings.
AB  - We studied brain perfusion in 19 patients with infantile neuronal ceroid
      lipofuscinosis (INCL), aged 13 months to 11 years, using 99mTc-HMPAO single
      photon emission computed tomography (SPECT). SPECT findings were compared with
      clinical manifestations and MRI findings. The typical SPECT findings at an early
      stage of INCL were bilateral anterior frontal, posterior temporoparietal and
      occipital hypoperfusion. Initially cerebral hypoperfusion was localized and
      symmetrical, whereas atrophic findings were more generalized. Reduction in
      cerebellar perfusion appeared later, as did cerebellar atrophy. Progression from
      mild to severe cerebral and cerebellar hypoperfusion was rapid, corresponding to
      the clinical progression. However, the perfusion of deep grey matter structures
      (basal ganglia and thalami), although atrophic on MRI, was often well preserved
      up to the terminal stage. Severe perfusion defects in INCL, which appeared
      approximately at the age of four, were associated with grave clinical
      manifestations and neuropathologic findings. Particularly, the early SPECT
      perfusion abnormalities may assist in the differential diagnosis between INCL and
      other neurode-generative diseases.

PMID- 8737821
TI  - Cobblestone lissencephaly with normal eyes and muscle.
AB  - Cobblestone lissencephaly is the characteristic brain malformation observed in
      Fukuyama congenital muscular dystrophy (FCMD), muscle-eye-brain disease (MEB),
      and Walker-Warburg syndrome (WWS). The diagnostic criteria for all three require
      the presence of congenital muscular dystrophy, and criteria for MEB and WWS
      require retinal abnormalities. We report three patients from two consanguineous
      families of Middle Eastern origin with cobblestone lissencephaly but no
      abnormalities of the eyes or muscle. Based on the current diagnostic criteria for
      the cobblestone lissencephaly syndromes, this disorder must be classified
      separately from the others, but it may well be allelic to MEB and WWS. Linkage
      studies have excluded the gene for this disorder from the region of the FCMD gene
      on chromosome 9q31-32.

PMID- 8737823
TI  - Brain perfusion SPECT in juvenile neuronal ceroid lipofuscinosis.
AB  - The juvenile neuronal ceroid-lipofuscinosis (JNCL) is a recessively inherited
      progressive encephalopathy. We studied 21 JNCL patients with a duration of
      illness of 1 to 17 years by 99mTc-HM-PAO single photon emission computed
      tomography (SPECT) and correlated the findings with clinical parameters. All
      patients had at least one hypoperfused brain area, the median number of such
      areas was 5 per patient. Parietally, occipitally, and in the cerebellar lobes
      hypoperfusion was usually mild whereas it was temporally more severe. Right
      parietal hypoperfusion correlated to neurological dysfunction.

PMID- 8737824
TI  - VEP and ERP abnormalities in children and adolescents with prepubertal onset of
      insulin-dependent diabetes mellitus.
AB  - Visual evoked sensory (VEP) and event-related potentials (ERP) were assessed in
      29 adolescents with insulin-dependent diabetes mellitus (IDDM) and in 29 controls
      matched for age and gender. Data were compared with clinical and psychometric
      measures, age at onset, duration of disease, and metabolic control. Analysis
      revealed no latency differences for the first cortical VEP component (P50) but a
      steadily increasing latency delay for subsequent VEP (N80, P100, N150, P200) and
      ERP components (P300) in the IDDM group compared to healthy controls. IDDM
      subjects showed highly significant latency prolongations (p < 0.001) for P100,
      N150 and P200 and P300 compared with healthy controls. A pathological VEP/ERP
      latency delay of more than 3 SD above the reference value range was observed in
      21 IDDM patients (72.4%). Psychometric outcome measures in IDDM subjects showed
      no significant performance deficits on the Raven SPMs relative to non-diabetic
      controls. In contrast to VEP and ERP anomalies, which were highly interrelated,
      there was no tendency for neurophysiological and psychometric abnormalities to be
      contemporarily present. Neither electrophysiological nor psychometric measures
      were correlated with age at onset, IDDM duration, quality of metabolic control,
      or the presence of peripheral neuropathy. These findings give evidence that 1)
      higher cognitive functions are frequently affected in adolescents even with
      prepubertal IDDM onset, 2) neurophysiological ERP analysis seems to detect minor
      neurocognitive restrictions, presently not affecting psychometric outcome, 3)
      altered neurophysiological parameters were present in more than 70% of IDDM
      subjects studied, and 4) functional CNS disturbances affecting neurocognition are
      apparently not correlated with metabolic parameters previously thought to be
      important predictors of CNS outcome, suggesting the presence of multifactorial
      influences affecting neurocognition in IDDM subjects.

PMID- 8737825
TI  - Outcome of persistent vegetative state following hypoxic or traumatic brain
      injury in children and adolescents.
AB  - Persistent vegetative state (PVS, apallic syndrome) has become a significant
      medical and social problem. The outcome of young people with PVS is a matter of
      great interest. Therefore, we analysed the outcome of 127 children and
      adolescents who were in PVS for at least 30 days following traumatic (n = 82) or
      hypoxic (n = 45) brain injury. After 19 months of follow-up, 84% of the patients
      of the traumatic brain injury (TBI) group, but only 55% of the hypoxic brain
      injury (HBI) group had left PVS (p < 0.001). The TBI patients regained
      consciousness earlier. Later than 9 months post trauma less than 5% of the
      patients of both groups left PVS. Hypoxic brain injury patients had a higher
      incidence of seizures (p = 0.01) and a higher seizure frequency. They had
      significantly more complications like pneumonia, gastrointestinal disturbance or
      myositis ossificans (= heterotopic ossification). Posttraumatic hyperthermia and
      autonomic dysfunctions were correlated with worse outcome in the TBI group, but
      not in the HBI group. Thirteen patients (16%) with TBI became independent in
      everyday life versus only two (4%) with HBI. These results underline the
      important contribution of hypoxia in severe and permanent brain impairment. They
      also may help to establish the prognosis of children in PVS.

PMID- 8737826
TI  - The posterior fontanelle: a neglected acoustic window.
AB  - The additional information, obtained when using the posterior fontanelle
      routinely as the second acoustic window, is illustrated in four infants. Three of
      them are full-term infants with hypoxic ischaemic encephalopathy. In newborn
      infants, who are still too unstable to be transported to the magnetic resonance
      unit, extensive damage in the occipital subcortical white matter and/or cortex
      can be visualised by performing cranial ultrasound through the posterior
      fontanelle.

PMID- 8737827
TI  - Delayed bilateral median nerve injury due to low-tension electric current.
AB  - A 6-year-old boy inserted an opened metal clip into a domestic electric outlet
      using the thumb and index fingers of both hands. He suffered low tension
      electrical shock with mild cutaneous signs. After a few weeks, he developed
      bilateral numbness and weakness of both hands. Electrophysiologic studies
      revealed bilateral median nerve sensorimotor axonal loss. Low tension electric
      shock could have produced delayed bilateral median nerve damage indirectly via
      spasm and thermal coagulation of the vasa nervorum. The pinching position of the
      fingers, the "circuit" of the metal clip, and the low resistance due to the
      thinness and moistness of child's skin may account for: 1) the absence of an
      electrical cutaneous burn and 2) easy volume conduction of current along the
      neurovascular bundle containing the median nerve.

PMID- 8737828
TI  - Association of congenital muscular dystrophy with hypoplasia of the lateral
      abdominal wall musculature and hypoplasia of the external genitalia.

PMID- 8737829
TI  - Smith-Lemli-Opitz syndrome: treatment with cholesterol and bile acids.

PMID- 8737830
TI  - Genetic differences and heritability of antibody response to Escherichia coli
      vaccination in young broiler chicks.
AB  - Broiler chicken lines, selected divergently for high (HC) or low (LC) antibody
      titer to Escherichia coli vaccination at an early age, were evaluated for
      antibody response at the S5 and S9 generations of selection. The full-pedigreed
      populations consisted of about 300 and 400 chicks per line in S5 and S9,
      respectively. At S5, all chicks were vaccinated at 10 d of age (VA10) and
      antibody titer was determined twice for each chick, at 8 and 12 d postvaccination
      (dPV). At S9, each line was divided into two equal groups; in the HC line, one
      group was vaccinated at 8 d of age (VA8), and the other at 10 d of age (VA10),
      whereas in the LC line, one group was VA10 and the other was VA12. Antibody
      titers were determined twice for each chick, 8 and 10 dPV. The effects of line,
      age at vaccination (VA), and days for antibody development (dPV) were tested, and
      the heritability of antibody titer was estimated for each line-VA-dPV set of
      data. The HC and LC lines differed significantly in the maturation process of
      their immune systems. The percentage of chicks with detectable antibody at 18 d
      of age (VA10-8 dPV) among HC chicks was significantly higher than among LC chicks
      (85 vs 48% in S5 and 96 vs 63% in S9). In S9, 90% of the HC chicks had already
      responded at 16 d of age and 100% at 18 d of age, whereas among the LC chicks,
      only 62% were positive at 18 d of age, increasing to no more than 98% at 22 d of
      age. The results demonstrates that selection of antibody titer to E. coli
      vaccination at 20 d of age actually affects the earliest age of immune response,
      as the immune system of the HC chicks matures earlier than that of the LC chicks.
      The HC S9 chicks at 8 dPV exhibited a fourfold higher antibody titer than their
      LC 8 counterparts. This difference further increased at 10 dPV, indicating that
      the lines differed not only in the level of antibody at a specific age, but also
      in their rate of antibody titer development. The highest estimate of heritability
      was very similar in both lines (0.44 and 0.42 in HC and LC, respectively).
      However, in the HC line this heritability was exhibited at 18 d of age, and only
      at 22 d in the LC line. Thus, both lines have a similar amount of genetic
      variation for early immune response, but in the HC line this variation is fully
      expressed 4 d earlier than in the LC line. These results suggest that selection
      for high or low antibody response in young chicks results in early or late
      antibody production, respectively. To maximize the efficiency of selection for
      early immune response, one must determine the best vaccination age and timing of
      antibody evaluation in any given population, and these values must be revalidated
      and updated as selection proceeds.

PMID- 8737831
TI  - Promoter and transcription of type X collagen gene in broiler chickens with
      tibial dyschondroplasia.
AB  - Type X collagen is produced exclusively in hypertrophic chondrocytes of the
      growth plate of the proximal tibiotarsus and is believed to play an important
      role during normal development from chondrogenesis to osteogenesis. Chondrocytes
      of chickens with tibial dyschondroplasia (TD) fail to attain full hypertrophy and
      the amount of type X collagen, being a marker of hypertrophy, is likely to be
      reduced. It is not clear whether transcriptional regulation is functional for
      expression of the type X collagen gene in TD birds. Nucleotide sequence of the
      type X collagen gene promoter was determined by sequencing PCR-based DNA clones.
      Nucleotide identity of this fragment between the normal and TD carriers was
      97.6%. Both normal and TD birds were similar in a putative transcription start
      site, the site of TATAA box, and neither had a CCAAT box. However, there were two
      gaps in TD carriers, four gaps in normals, and five nucleotide substitution
      sites. By rapid amplification of cDNA ends by PCR (RACE-PCR), transcription of
      the gene was assessed using total RNA and mRNA from both normal chondrocytes and
      TD lesions at 3 and 4 wk of age. The RACE-PCR product for type X collagen mRNA
      was detectable in both normal and TD birds at two stages. No difference was found
      between them. This result does not support the hypothesis that transcriptional
      regulation of type X collagen gene is important in TD development of chickens.
      Variations in the promoter region did not affect transcription of type X collagen
      gene in TD carrier chickens.

PMID- 8737832
TI  - Effects of breeder hen age and dietary fat on embryonic and neonatal broiler
      serum lipids and glucose.
AB  - In two experiments, the effects of dietary fat and breeder hen age on relative
      yolk sac weight (RYSW) and total serum cholesterol (CHOL), high (HDLC) and low
      (LDLC) density lipoprotein cholesterol, triglycerides (TRI), and glucose (GLU)
      were monitored in broiler embryos and chicks. In Experiment 1, embryos at 18 d of
      incubation and chicks at hatch were sampled from eggs laid by breeder hens at 26
      (young), 36, and 48 wk of age. No dietary effects were noted in either
      experiment; however, chicks from young hens exhibited elevated serum CHOL, HDLC,
      LDLC, and lower GLU when compared with chicks from hens at either 36 or 48 wk of
      age. Additionally, embryos from young breeders displayed a lower RYSW at 18 d of
      incubation. Conversely, by hatch there was no difference in RYSW among offspring
      from different aged hens. In Experiment 2, newly hatched chicks were sampled from
      breeder hens at 36, 51, and 64 wk of age. Dietary effects were also not evident
      in this experiment; however, chicks from 51-wk-old breeders displayed the highest
      and lowest serum HDLC and TRI, respectively, compared to the other two age
      groups, whereas chicks from either 51- or 64-wk-old breeders exhibited higher
      levels of CHOL than those at 36 wk. Chicks from 64-wk-old breeders displayed an
      increase in LDLC when compared with the other two ages. These data suggest that
      serum concentrations of lipids and GLU, and RYSW in 18 d embryos and newly
      hatched chicks are influenced by hen age and not by added dietary fat.

PMID- 8737833
TI  - Beak trimming of turkeys. 1. Effects of three methods of beak trimming on body
      weight and mortality of six genetic lines.
AB  - An experiment was designed to compare BW and mortality of turkeys when three
      methods of beak trimming were utilized. Turkeys from six genetic lines were
      assigned to three beak trimming methods: arc beak trimming at hatching, hot-blade
      block trimming at 13 d, or hot-blade top-beak-only trimming at 13 d. Beak
      trimming method influenced 8-wk BW of three lines of females, but did not affect
      female BW at 16 wk. Beak trimming method influenced 8-wk BW of males from one
      line and 16-wk BW of a different line. There were no effects of method of beak
      trimming on 20-wk BW of either males or females from any line. Neither lines nor
      beak treatments differed in mortality.

PMID- 8737834
TI  - Effects of feed antibiotic avoparcine on organ morphology in broiler chickens.
AB  - Groups of 90 male broilers each were administered the antibiotic avoparcine mixed
      into feed in concentrations of 7.5, 10, and 15 ppm and achieved a higher mean
      body weight than the controls fed without this admixture. At the end of the 70-d
      fattening period, histological examination was carried out on selected
      individuals. The small intestine, liver, bursa of Fabricius, thymus, thyroid
      gland, pancreas, kidneys, heart, and skeletal muscle were observed on paraffin
      sections stained with hematoxylin and eosin. Cell proliferation was assessed in
      the liver and small intestine by means of bromodeoxyuridine labeling. The
      exposure to avoparcine resulted in a decreased cell proliferation in both tissues
      when compared to controls. In addition, hypertrophy of the hepatocytes and
      development of reactive lymphoid tissue in the bursa of Fabricius, which occurred
      in the controls, were absent in the treated animals. These observations indicate
      that the growth-promoting effect of avoparcine is related to a restriction in the
      host animals of responses to intestinal bacteria. No adverse pathological changes
      were observed in the examined tissues, indicating that avoparcine was well
      tolerated.

PMID- 8737835
TI  - Responses of growing and finishing turkey toms to dietary lysine.
AB  - The present study investigates the lysine requirements of British United Turkey
      (BUT) Big 6 turkey toms from 8 to 12 and from 16 to 20 wk of age. Growth, feed
      conversion, and carcass quality responses to increasing dietary lysine levels
      were measured. From 8 to 12 wk of age (4.0 to 8.8 kg live weight), about 1.20%
      (4.0 g/Mcal ME) lysine in the diet was found to be adequate to obtain optimum
      growth and feed conversion, Nitrogen retention also tended to increase with
      elevated dietary lysine levels in growing turkey toms. From 16 to 20 wk of age
      (13.1 to 18.5 kg live weight), the highest lysine level of 0.96% (3.0 g/Mcal ME)
      appeared to be insufficient to maximize weight gain. It is concluded, therefore,
      that the dietary lysine requirement of finishing turkey toms is 0.96% lysine or
      higher. In addition to the growth response, a marked increase in breast meat
      deposition in response to dietary lysine could be observed in finishing turkeys.
      Increasing dietary lysine decreased intramuscular fat content and grill loss and
      increased the protein level in breast meat.

PMID- 8737836
TI  - Changes in body composition and adipocyte cellularity of male broilers subjected
      to varying degrees of early-life feed restriction.
AB  - Three experiments were conducted to determine growth performance, body
      composition changes, and adipocyte characteristics of male broilers subjected to
      early-life feed restriction. The purpose of Experiment 1 was to determine 42-d
      growth performance and body composition changes. Treatments used were full-fed
      control and 50% physical feed restriction during the period 6 to 12 d of age.
      Experiment 2 was conducted to determine the adipocyte characteristics during and
      after feed restriction to 42 d of age. An additional treatment involved gradual
      refeeding following the feed restriction period. Experiment 3 was designed to
      test the effect of feeding different types of dietary fat during realimentation
      on the abdominal fat pad (AFP) size, and lasted until 18 d of age. Three types of
      fats were tested, namely animal-vegetable (A-V) blend, flax oil, and animal
      tallow, each represented by full-fed and feed-restricted treatments. Complete
      compensatory growth by feed-restricted birds relative to controls was not
      achieved by 42 d in either Experiments 1 or 2. Early feed restriction resulted in
      lower body fat percentage at 12 d (P < 0.05), although by 42 d a higher rate of
      fat deposition mainly by hypertrophy of adipocytes resulted in no difference in
      fatness. Gradual reintroduction into ad libitum feeding did not alter such
      adipocyte hypertrophy nor improve compensatory growth response during refeeding.
      There was consistent improvement in feed efficiency associated with early-life
      feed restriction (P < 0.05). The use of different types of dietary fat did not
      effect the AFP when expressed as percentage body weight. Birds that were fed A-V
      blend during the refeeding period had bigger AFP (grams per bird), a situation
      that is attributable to differences in body weight. Attainment of growth
      compensation by the feed-restricted broilers apparently requires a more prolonged
      growth period or a less severe feed restriction program than that used here.
      Saturation of dietary fat has no effect on realimentation characteristics of the
      broiler.

PMID- 8737837
TI  - The effects of supplemental microbial phytase on the performance and utilization
      of dietary calcium, phosphorus, copper, and zinc in broiler chickens fed corn
      soybean diets.
AB  - A 3-wk feeding trial with 180 sexed day-old broiler chickens was conducted to
      study the efficacy of microbial phytase (Natuphos 1000) on growth performance,
      relative retention of P, Ca, Cu, and Zn, and mineral contents of plasma and bone.
      Treatments involved a normal P level corn-soybean diet, a low-P diet, and a low-P
      plus phytase (600 phytase units/kg) diet. Phytase supplementation increased (P <
      or = 0.05) body weight in male and female chickens by 13.2 and 5.8%,
      respectively, at 21 d. The improvements yielded body weights comparable to those
      obtained on the normal P diet. Phytase supplementation overcame (P < or = 0.05)
      the depression of feed intake observed on the low-P diet. Treatments had no
      effect on feed:gain ratio. Phytase supplementation of the low-P diet increased (P
      < or = 0.05) the relative retention of total P, Ca, Cu, and Zn by 12.5, 12.2,
      19.3, and 62.3 percentage units, respectively, in male chickens. Microbial
      phytase increased the plasma P by 15.7% and reduced (P < or = 0.05) the Ca
      concentration by 34.1%, but had no effect on plasma concentrations of Cu or Zn.
      Phytase supplementation increased the percentage ash in both head and shaft
      portions of dry, fat-free tibia bone to a level comparable to that of the normal
      P diet. Phytase supplementation had no effect on the concentration of any of the
      minerals measured in whole tibia ash but did increase (P < or = 0.05) the DM
      percentage of P and Ca min tibia head of male chickens by 0.65 and 1.4 percentage
      units, respectively. These results show that microbial phytase supplementation of
      a low-P diet increased growth and relative retention of total P, Ca, Cu, and Zn
      and improved bone mineralization in broiler chickens.

PMID- 8737838
TI  - Sulfur amino acid requirement and cystine replacement value of broiler chicks
      during the period three to six weeks posthatching.
AB  - Three experiments were conducted with commercial broiler chicks to determine the
      SAA requirement during the growth period 3 to 6 wk posthatching. A 20% CP corn
      peanut meal basal diet (3,200 kcal ME(n)/kg) was analyzed to contain 0.23% Met
      and 0.28% cystine. True digestibility assessment in cecectomized cockerels
      revealed that Met and cystine in the basal diet were 81 and 75% digestible,
      respectively. Therefore, the basal diet contained 0.19% digestible Met and 0.21%
      digestible cystine. When fully fortified with DL-Met, growth rate and feed
      efficiency of chicks fed the corn-peanut meal diet were equal to that of chicks
      fed a 20% CP Met-fortified corn-soybean meal diet. In the SAA requirement assay,
      Ross x Hubbard male chicks were fed graded increments of DL-Met (0.03%) and L
      cystine (0.03%) to achieve digestible SAA concentrations of 0.40, 0.46, 0.52,
      0.58, 0.64, and 0.70%. Weight gain and feed efficiency responded quadratically (P
      < 0.01) to increasing doses of SAA. The estimated requirement for maximal feed
      efficiency was higher than that for maximal weight gain. Both visual appraisal
      and curve fitting procedures suggested a requirement of close to 0.61% digestible
      SAA. When extrapolated to a corn-soybean meal diet where SAA true digestibility
      is 87.5%, the total SAA requirement calculates to be 0.70% of the diet. However,
      because commercial corn-soybean meal diets typically contain supplemental Met,
      which is only 81% efficient (wt:wt) in furnishing cystine, the estimated total
      SAA requirement for chicks fed 20% CP Met-fortified corn-soybean meal diets with
      3,200 kcal of ME/kg would probably approximately 0.72% of the diet. A DL-Met vs L
      cystine supplementation assay suggested that digestible cystine can supply no
      more than 52% of the total requirement for digestible SAA of chicks during the 3-
      to 6-wk growth period.

PMID- 8737839
TI  - Effect of orally administered Eubacterium coprostanoligenes ATCC 51222 on plasma
      cholesterol concentration in laying hens.
AB  - Thirty normocholesterolemic laying hens were used to investigate the effect of
      oral administration of Eubacterium coprostanoligenes on plasma cholesterol
      concentrations. Hens were divided randomly into three treatment groups (active,
      inactive, and control) with 10 hens in each group. The active group received 0.5
      mL of E. coprostanoligenes suspension (approximately 2 x 10(7) cells per
      milliliter) daily for 4 wk; the inactive group received the same dosage of killed
      (boiled) bacterial suspension; and the control group received no supplemental
      bacteria. After bacterial feeding, the coprostanol to cholesterol ratio in feces
      of the active group was significantly greater than ratios of the inactive and
      control groups, indicating that E. coprostanoligenes was colonized in the
      intestine of hens and was converting intestinal cholesterol to coprostanol.
      Plasma cholesterol concentrations, however, were not affected by the bacterial
      treatment.

PMID- 8737840
TI  - Preliminary linkage map of the chicken (Gallus domesticus) genome based on
      microsatellite markers: 77 new markers mapped.
AB  - Microsatellite polymorphisms are finding increasing use in genetics. The
      objectives of this study were 1) to enlarge the number of markers to contribute
      to a well-defined linkage map of the chicken genome; and 2) to create a
      preliminary linkage map only based on microsatellite markers. The need for
      microsatellite markers is high for performing a whole genome scan for the
      identification of quantitative trait loci. Seventy-seven newly developed
      microsatellite markers that were polymorphic on either one or both of the
      reference populations were mapped and in combination with all previously
      described markers, used to construct a preliminary linkage map of the chicken
      genome. The 128 microsatellite markers mapped thus far cover 23 of the 38 linkage
      groups of the East Lansing reference population. In the case of the Compton
      reference population, 20 linkage groups out of 40 are covered with microsatellite
      markers. No linkage was found in the East Lansing population with five markers,
      and in the case of the Compton population four markers were unlinked. About 42
      and 32% of the East Lansing and Compton maps, respectively, were covered by the
      128 microsatellite markers. The microsatellite markers are well dispersed among
      the various linkage groups and there was no evidence for clustering of the
      markers within the map. With the 38 markers that were mapped on both reference
      populations, 10 of the East Lansing linkage groups could be associated with 13 of
      the Compton linkage groups.

PMID- 8737841
TI  - Age effect of male and female broiler breeders on sperm penetration of the
      perivitelline layer overlying the germinal disc.
AB  - An experiment was conducted to test the effect of age (male and female) on the
      number of spermatozoa penetrating the perivitelline layer (PL) overlying the
      germinal disc (GD) in broiler breeders. Eighty young broiler breeder hens (39 wk
      old, Y), and 80 old spent broiler breeder hens (69 wk old, O) were randomly
      divided into eight groups of 20 hens each by age. Hens were inseminated weekly
      for 4 consecutive wk with 5 x 10(7) pooled sperm/50 microL from either young or
      old broiler breeder males. Sperm penetration (SP) of the PL at the GD was
      assessed in a random sample of 12 oviposited eggs from each hen group for each
      day postinsemination, with the remainder of the eggs incubated for 10 d to obtain
      fertility values. For the main effect of sex, and for age within sex, there were
      differences in mean SP (7.3 vs 4.8; Y vs O hens; P < 0.02) and fertility (73.7 vs
      54.9%; Y vs O hens; P < 0.002) values. Old males had higher mean SP values and
      fertility (7.2 and 70.6%) than young males (4.8 and 58.0%; P < 0.03 and 0.01,
      respectively). Following artificial insemination of a constant number of sperm,
      age of hens appears to contribute more to the decrease in SP and fertility than
      the age of male broiler breeders. Eggs were obtained from naturally mated broiler
      breeder flocks from different strains (A and B), lines (male and female), and
      ages. There was an effect on overall mean SP values due to strain (105.8 vs 78.6
      holes per GD area; Strains A and B, respectively; P < 0.0001), and line within
      Strain B (106.4 vs 50.8 holes per GD; male and female line, respectively; P <
      0.0001). There was a quadratic relationship between SP of the PL and age in
      Strain A with values ranging from 153.3 to 20.0 holes per GD area (P < 0.003). In
      Strain B, SP holes in the PL decreased in the male line due to age (127.8 to 59.7
      per GD; P < 0.01), with an effect of age on the female line also (62.1 vs. 37.8
      holes per GD; P < 0.05).

PMID- 8737842
TI  - The suppressive effects of testosterone on growth in young chickens appears to be
      mediated via a peripheral androgen receptor; studies of the anti-androgen ICI
      176,334.
AB  - ICI 176,334 is a nonsteroidal anti-androgen that has been shown to selectively
      block peripheral androgen receptors in rats and is presumed to do so in chickens.
      In chickens, androgens stimulate secondary sexual characteristics (e.g., comb),
      but inhibit growth and the immune tissues. The present study examined the effect
      of dietary ICI 176,334 (5 or 25 mg/kg body weight) on growth in chickens in the
      presence or absence of testosterone treatment (as 1-cm long silastic implants).
      Treatments began at 2 wk of age and continued through 6 wk of age. Testosterone
      alone reduced body growth (average daily gain and shank-toe length, together with
      weights of the body, skeletal muscle, and the bursa of Fabricius, an immune
      tissue), and stimulated comb development. At the low dose (5 mg/kg), ICI 176,334
      alone had no effect on body growth or organ weight with the exception that comb
      weight was reduced. At the high dose (25 mg/kg), ICI 176,334 decreased growth
      (body weight, average daily gain, and shank-toe length) and organ weights (breast
      muscle, bursa of Fabricius, testis, and comb weights). This effect may represent
      a toxicity. As might be expected with an anti-androgen, ICI 176,334 (at either 5
      or 25 mg/kg) completely suppressed the stimulation of comb growth evoked by
      testosterone. Similarly, ICI 176,334 (5 mg/kg) overcame, albeit partially, the
      growth-suppressive effects of testosterone (on body weight, average daily gain,
      shank-toe length, and breast muscle weight) and also had inhibitory effects on
      the weights of the testis and bursa of Fabricius. The anti-androgen, ICI 176,334,
      did not influence the reduction in circulating concentrations of luteinizing
      hormone occurring after testosterone treatment. The present data are consistent
      with the growth-suppressive effects of testosterone in chickens being mediated
      via a peripheral androgen receptor. No effects of either testosterone or ICI
      176,334 were observed on circulating concentrations of insulin-like growth factor
      I despite the marked changes in growth rate.

PMID- 8737843
TI  - Influence of male broiler breeder dietary energy intake on reproduction and
      progeny growth.
AB  - A study was conducted to test the effects of dietary energy intake on
      reproduction in genetically similar broiler breeder males and on the subsequent
      growth of their progeny. Fifty-nine 1-d-old pedigree broiler breeder male chicks
      were raised to breeding age. At 33 wk of age, 33 males were chosen and placed in
      one of three groups of 11 males per group and fed either 370, 330, or 290 kcal
      per bird per d. Each group contained both full and half brothers and had similar
      6- and 33-wk mean body weights. There was a significant negative effect of
      decreased dietary energy intake on sperm concentration and total live sperm per
      milliliter of ejaculate, whereas there was no significant effect on ejaculate
      volume or percentage dead sperm per ejaculate. Four groups of hens (21 wk of age)
      with 18 hens per group, were randomly assigned to each male dietary treatment
      group. Hens were artificially inseminated with 50 microL neat pooled semen from
      one of the three male treatment groups. There was a significant linear effect of
      diet on fertility, with no significant effect on hatch of fertile, hatch of eggs
      set, or embryonic mortality. There was no effect of sire energy intake on
      offspring body weights at 0, 3, or 6 wk of age. Hens were similarly artificially
      inseminated and sperm penetration determined for 9 consecutive d
      postinsemination. There was a significant quadratic relationship between sperm
      penetration of the perivitelline layer overlying the germinal disc and day
      postinsemination for each of the three male treatment groups. In addition, mean
      sperm penetration was 62.3, 42.9, and 6.6 holes in the germinal disc
      perivitelline layer for the high, medium, and low energy groups, respectively.
      Following 16 wk of dietary energy treatment, there was a significant linear
      effect of diet on mean testes weight, mean testes weight as a percentage of male
      body weight, and male body weight.

PMID- 8737844
TI  - Objective measurement of sperm motility based upon sperm penetration of Accudenz.
AB  - When a suspension of rooster sperm was overlaid upon 6% (wt/vol) Accudenz,
      immotile sperm did not enter but motile sperm entered rapidly. The absorbance of
      the Accudenz layer increased as a result. These phenomena were used to measure
      sperm motility objectively at body temperature. The intra-assay coefficient of
      variation (CV) was 2.6% (n = 3). When roosters (n = 36) were ejaculated
      repeatedly and sperm motility data analyzed by two-way ANOVA, a male effect was
      observed (P < or = 0.001). When roosters were ranked by mean motility scores (n =
      3 evaluations per male) and representative males selected as semen donors, a
      difference in fertility (P < or = 0.001) was observed between males characterized
      by minimal and maximal sperm motility. Frequency analysis with data from a second
      flock of roosters (n = 100) revealed a normal distribution. Roosters categorized
      by average sperm motility (n = 18) or sperm motility greater than one standard
      deviation above the mean (n = 17) were selected for further analysis by repeated
      measurements. A split-plot ANOVA revealed a difference between categories (P < or
      = 0.0001) and variation among males within a category (P < or = 0.0001). In
      contrast, sperm motility was independent of time and there was no interaction
      between category and time. Thereafter, five roosters from each group were
      ejaculated weekly and interassay CV estimated with semen pooled by category (n =
      3 observations per category). During this interval, sperm motility of average
      roosters was 55 +/- 5.9% of that of roosters within the high motility category.
      Interassay CV were 18.1 and 9.2% for roosters originally categorized by average
      and high sperm motility, respectively. The assay described has potential for: 1)
      selecting males based on sperm motility, and 2) standardizing the measurement of
      poultry sperm motility.

PMID- 8737845
TI  - A new method for rapid determination of sperm concentration in turkey semen.
AB  - The routine determination of sperm concentration not only provides a measure of
      semen quality but also supplies a means of delivering precise sperm numbers in
      modern artificial insemination (AI) programs. Methods for estimating sperm
      numbers in laboratory settings (e.g., hemacytometer) are not practical for use in
      breeding facilities. A microprocessor-controlled semen analyzer (Densimeter,
      Model 534-B-Mod1, Animal Reproductive Systems) is commercially available for
      evaluating stallion semen. We calibrated and modified the semen analyzer to
      determine sperm concentration in turkey semen and to provide information on the
      required dilution for a constant AI dose. To calibrate the semen analyzer for
      turkeys, six samples of pooled semen (10 toms per sample) were collected by
      abdominal massage. A dilution curve of undiluted and 1:0.5, 1:1, 1:1.5, 1:2, 1:3,
      1:5, and 1:10 diluted semen was established using Beltsville Poultry Semen
      Extender. Sperm concentration in diluted samples was determined by hemacytometer
      counts. The hemacytometer counts were used to develop an equation for estimating
      sperm concentration from the semen analyzer's absorbance readings and the
      equation programmed into the instrument. The newly developed program on the semen
      analyzer was subsequently validated by comparing instrument values for sperm
      concentrations with concurrent hemacytometer counts, which compared well to
      concentrations determined by a previously calibrated photoelectric colorimeter
      (Klett). Correlation coefficients between the semen analyzer and hemacytometer
      counts and the Klett and hemacytometer counts were r = 0.996 and r = 0.992,
      respectively (P < 0.001). The semen analyzer method was accurate and precise and
      could be beneficial to commercial turkey AI programs because it is easy to use,
      requires limited technological skills, and provides results for determining sperm
      concentration and AI dose in approximately 1 min.

PMID- 8737846
TI  - Comparative growth and development of Nicholas and hybrid toms from 16 to 82 days
      and effects of protein restriction from 0 to 59 days on growth of hybrid toms
      through 125 days of age.
AB  - The objective of this experiment was to study age and diet effects on serial
      growth of economically important carcass parts of Nicholas (NIC) and Hybrid (HYB)
      toms. At approximately 14-d intervals from 16 to 82 d, BW and the weight of
      selected carcass parts were compared in toms from both commercial strains. There
      were no overall strain differences in BW, although NIC toms were heavier from 31
      to 72 d, which resulted in a significant strain by age interaction (P < or =
      0.021). The absolute weight of the Pectoralis major (PMAJ; P < or = 0.022) and
      tibia plus associated muscles (Drum; P < or = 0.051) were increased in NIC toms.
      The relative weight of the PMAJ (P < or = 0.004) and abdominal fat (72 and 82 d;
      P < or = 0.023) also were heavier in NIC toms. The relative weight of the drum
      and Gastrocnemius muscle (GAS-TROC) was heavier in HYB toms, however (P < or =
      0.001). A separate set of HYB poults was fed a diet deficient in protein or
      lysine (PD) from 0 to 8 wk and their growth and carcass development were compared
      with those fed a Control diet (NRC, 1984). Comparisons also were made at
      approximately 14-d intervals from 16 to 125 d. The PD diet from 0 to 8 wk
      significantly reduced BW and absolute breast muscle and leg portion weights. The
      relative weight of the PMAJ and Pectoralis minor (PMIN) were also reduced in toms
      fed the PD diets but the thigh and drum (125 d) were increased.

PMID- 8737847
TI  - The influence of temperature on broiler breast muscle shortening and
      extensibility.
AB  - The purpose of this study was to characterize the influence of temperature on
      muscle shortening and extensibility in broiler breast muscle (Pectoralis major).
      The extent of prerigor muscle shortening has been shown to affect the ultimate
      tenderness of meat, whereas a decrease in extensibility has traditionally been
      used to define rigor mortis in muscle. Muscle shortening over time was determined
      at three incubation temperatures: 0, 23, and 41 C. Shortening was measured on
      intact and excised muscles, as well as on muscle strips with and without attached
      weight (200 g). The time a muscle strip needed to reach loss of extensibility was
      also determined at each of the three incubation temperatures. The intact and
      excised muscles showed some evidence of both cold and rigor (hot) shortening. No
      extreme shortening effects were found in the muscle strips incubated with or
      without attached weight. The use of muscle strips to predict intact muscle or
      excised whole muscle shortening in a complex muscle such as poultry Pectoralis
      may be limited. The time required to loss of extensibility of the muscle strips,
      i.e., rigor completion, was 5.5, 4.5, and 0.8 h at 0, 23, and 41 C, respectively.
      The results show that cold-induced shortening may contribute to toughening of
      early deboned broiler breast muscle, but its impact on commercial processing and
      subsequent meat tenderness does not appear to be consistent.

PMID- 8737848
TI  - Comparison between irradiated and thermally pasteurized liquid egg white on
      functional, physical, and microbiological properties.
AB  - A comparative study was undertaken to determine the effect of irradiation and
      thermal pasteurization on the functional, physical, and microbiological
      properties of liquid egg white (LEW). The LEW was irradiated or thermally
      pasteurized then stored at 4 C for 3 mo. Both treatments destroyed the inoculum,
      Salmonella typhimurium. The microbial growth rate was slower in the irradiated
      LEW than in the thermally pasteurized treatment. Irradiated samples had 47% lower
      foam drainage and more stable viscosity than samples that were thermally
      pasteurized. Volume of angel food cake prepared with irradiated or pasteurized
      LEW decreased 48 and 57%, respectively, after 90 d. Color did not differ between
      treatments. Ionizing radiation is an alternative processing method that inhibits
      microbial growth and helps maintain functionality of LEW.

PMID- 8737849
TI  - Carcass yield and weep loss from fast-food cuts after processing broilers using
      extremes in stunning current and slush-ice chilling.
AB  - Six-week-old broilers were compared in yield and weep loss when stunned using
      either 25 or 125 mA current followed by slush-ice chilling where resultant
      carcasses were either held static for 4 h or subjected to 45 m of tumbling.
      Treatments were factorially arranged among the populations of 32 pens (24 birds
      per pen) that had been reared under common conditions. Tumbling increased chill
      water uptake, abdominal fat content, and yield of whole carcasses, whereas no
      differences occurred as a result of the stunning treatments. Carcasses were
      separated into a nine-piece cut immediately after chilling. All parts lost weight
      from weepage during the subsequent 24 h, and weep from total parts was greater
      when carcasses had been tumbled than held static. Keel portion breasts and
      drumsticks continued a weight advantage from water uptake with tumble chilling,
      but wings, thighs, and split breast lost this additional water and were similar
      to those respective parts static chilled. High stunning current led to an
      increased amount of keel portion breast, regardless of chilling treatment, with
      subsequent weep not being affected. Alterations in yield that occur because of
      chilling procedure are substantial and not equivalent among parts, whereas
      stunning has little impact and is focused on the breast.

PMID- 8737850
TI  - Texture evaluations of cooked, diced broiler breast samples by sensory and
      mechanical methods.
AB  - The texture of cooked chicken breast is usually determined on intact pieces or
      strips that are representative of the muscle. Researchers emphasize the
      importance of uniformity of sample size and orientation of fibers to the shearing
      blades to ensure consistent data from instruments such as shear devices. For
      sensory evaluations, sample pieces of chicken breasts presented to panelists are
      often sized as single 2-cm2 or several 1-cm2 pieces. In this study, two sensory
      and two mechanical procedures were evaluated for efficacy in discerning texture
      differences in 1-cm2 pieces of cooked chicken. Three postmortem deboning times
      (2, 6, and 24 h) provided a texture quality spectrum. Sensory characteristics
      were evaluated by descriptive analysis trained panel (DA-TP) and by category
      scales-untrained panel (CS-UP). Twenty-gram breast portions of 1-cm2 pieces were
      evaluated using a multi-blade Allo-Kramer (AK) shear blade. Warner-Bratzler (WB)
      shear values of intact 1.9-cm-wide strips were also recorded. Discriminant
      analysis classification based on CS-UP gave higher error rates (probabilities of
      misclassification) than classification based on DA-TP. The CS-UP error rates were
      0.36 (tender) and 0.65 (juiciness). The error rate of classification by DA-TP was
      0.21. Error rates for classification by mechanical devices were 0.30 for WB and
      0.21 for AK. Sample size is a consideration in texture evaluation protocols.
      Smaller sample pieces appear to mask differences in initial chew characteristics
      and in juiciness that are due to deboning time.

PMID- 8737851
TI  - Should hepatitis C positive donors be accepted for renal transplantation?

PMID- 8737852
TI  - Challenges and evolving contributions of epidemiology in nephrology and
      hypertension.

PMID- 8737853
TI  - Salt sensitivity: does it play an important role in the pathogenesis and
      treatment of hypertension?
AB  - Abundant data confirm a role for sodium intake in human blood pressure and for
      the pathogenesis and treatment of some forms of hypertension. New information
      concerning mechanisms for the effect of salt on blood pressure, as well as the
      relationship between salt intake and the heart and kidneys, is reviewed.

PMID- 8737854
TI  - Blood pressure J-curve: is it cause or effect?
AB  - Clinical trials have demonstrated that antihypertensive therapy leads to the
      prevention of stroke, consistent with that predicted by epidemiological data. In
      contrast, in the same studies, the reduction in coronary artery disease events
      has been substantially less than predicted. Many possible explanations have been
      proposed to account for this shortfall in the reduction of disease produced by
      antihypertensive therapy. One suggestion has been that too great a fall in
      diastolic pressure during treatment actually increases the risk of myocardial
      infarction. A substantial body of data taken from clinical trials has
      consistently demonstrated a J-shaped association of diastolic pressure and
      coronary events. Some studies suggest that this J-shaped association is limited
      to those with coronary disease, and that the J-phenomenon is the result rather
      than the cause of atherosclerotic disease of the aorta. A prospective study is
      underway to resolve this issue. Meanwhile, the cautious physician is advised to
      seek a moderate decline in diastolic pressure to a level greater than 80 mmHg.

PMID- 8737855
TI  - 1995: the year of the calcium antagonist controversy.
AB  - The year 1995 has been an unsettling one in the history of the treatment of
      hypertension and ischemic heart disease. A fierce debate has sprung up about the
      safety of calcium antagonists, particularly the dihydropyridine nifedipine. A
      widely publicized case-control study showed that compared with diuretics and beta
      blockers, short-acting calcium antagonists, when used in the treatment of
      hypertension, were associated with a higher risk of myocardial infarction, an
      effect which appeared to be dose related. A second study focused on clinical
      trials of nifedipine in patients primarily with acute myocardial ischemia
      syndromes. The meta-analysis showed an increased risk in the relative mortality
      rate of 1.16 associated with the use of short-acting nifedipine at doses of 80
      mg/day or higher. The mechanisms responsible for these results were also
      discussed. Both publications were accompanied by editorials, and there were
      subsequently other commentaries published which pointed out weaknesses in the
      design, conduct, analysis and interpretation of the studies, and these have also
      been reviewed. Arising from this controversy, important questions have been
      raised which need to be addressed. First, are the data valid and are these drugs
      safe? If not, can the data be extrapolated from short-acting dihydropyridines, to
      the newer formulations and other sub-classes of calcium antagonists? Second, do
      these agents reduce cardiovascular morbidity and mortality? Finally, what are the
      alternatives to their use and the clinical implications? These studies have
      raised questions about safety, and there is little evidence to show any actual
      benefit on the incidence of cardiovascular events. For most patients there are
      clinically tested and proved therapeutic alternatives, i.e. diuretics and beta
      blockers, and therefore the burden of proof must now be on those who primarily
      recommend the use of calcium antagonists. Recommendations and guidelines for
      treatment, where the primary goal is to reduce cardiovascular morbidity and
      mortality must be supported by adequate data.

PMID- 8737856
TI  - Microalbuminuria: prognostic implications.
AB  - Microalbuminuria is the presence of albumin above the normal but below the
      detectable range with the conventional urine dipstick methodology.
      Microalbuminuria is present in a variety of renal and non-renal diseases but only
      recently has its importance as a prognostic indicator been appreciated. It is an
      independent risk factor for renal mortality in patients with insulin-dependent
      diabetes mellitus and most probably for those with non-insulin-dependent diabetes
      mellitus. Moreover, it is associated with a four- to sixfold increase in
      cardiovascular mortality in diabetic subjects. Its role as a prognostic indicator
      in non-diabetic subjects is controversial. The available data suggest that it is
      not an independent risk factor in patients without diabetes, including
      hypertensive subjects. Moreover, in this latter group it appears to be simply a
      reflection of events that result in tissue injury from elevated arterial
      pressures rather than an initiator of injury. The converse may be true in the
      diabetic patient. A large body of data also exists to support the notion of early
      aggressive intervention to attenuate the rise of microalbuminuria with blood
      glucose control. In addition, agents such as angiotensin-converting enzyme
      inhibitors attenuate both the rise in microalbuminuria and progression of insulin
      dependent diabetes mellitus nephropathy. Fewer but similar findings have been
      reported for subjects with non-insulin-dependent diabetes mellitus nephropathy.
      Thus, microalbuminuria should be assessed annually in all diabetic subjects.
      Routine screening for microalbuminuria in hypertensive non-diabetic subjects is
      not recommended at this time.

PMID- 8737857
TI  - Quality of patient care in the Medicare End-Stage Renal Disease Program: the
      basis and implementation of the 1994-1997 End-Stage Renal Disease Health Care
      Quality Improvement Program.
AB  - Substantial changes have occurred in the quality assurance and improvement
      programs conducted by the Health Care Financing Administration in the Medicare
      End-Stage Renal Disease Program. This review is a brief description of these
      changes and an introduction to the health policy, epidemiology, health services
      research, clinical nephrology, and statistical process control literature that is
      the basis for this initiative.

PMID- 8737858
TI  - Measuring effectiveness and outcomes of interventions for renal disease.
AB  - Effectiveness research, often called patient outcome research, is an evolving
      research discipline that attempts to provide information about the appropriate
      use of medical practices. This field of research uses epidemiological methods
      (observational and randomized controlled trials), analyses of variation and
      outcomes in medical practices, formal literature reviews and meta-analyses,
      quality of life measurement, decision analysis, patient preference assessment,
      patient satisfaction assessment, and economic and cost-effectiveness analysis.
      Several recent studies have applied a variety of these methods to provide data
      that will assist health professionals in the field of nephrology to make more
      informed clinical decisions. More of these studies are needed as new
      interventions are developed and tested in an environment where policy makers are
      asking how much value these interventions add and at what cost.

PMID- 8737859
TI  - Analgesics and chronic renal disease.
AB  - Intake of analgesics has been associated with the presence of chronic renal
      diseases in a number of studies. Phenacetin was the first drug to be linked with
      chronic renal disease. Four out of five case-control studies that have examined
      this issue have also demonstrated an association of acetaminophen use with renal
      disease. Non-steroidal anti-inflammatory drugs have not been available for a long
      enough time to evaluate risk associated with their use. Several studies suggest
      that mixtures of analgesics are most harmful to the Kidney. The National Kidney
      Foundation recently issued a position paper on analgesics and the kidney that
      provides guidance to patients and providers.

PMID- 8737860
TI  - Update on pathogenesis, markers and management of diabetic nephropathy.
AB  - Experimental animal models and cell culture techniques, highlighting the central
      role of glucose metabolism, have provided important insight into the pathogenesis
      of diabetic nephropathy. Microalbuminuria and other candidate phenotypic or
      genotypic markers for the early onset of disease are discussed. Management
      recommendations center around strict glycemic control and the normalization of
      blood pressure by angiotensin-converting enzyme inhibitors.

PMID- 8737861
TI  - Adhesion molecules in renal disease.
AB  - This review updates the advances in basic and clinical studies of adhesion
      molecules in renal disease that have appeared in 1995. The primary focus is on
      ischemia and transplantation.

PMID- 8737862
TI  - Immunomodulatory function of major histocompatibility complex-derived peptides.
AB  - Recent advances with regard to the structure and function of the major
      histocompatibility molecules have given rise to a better understanding of T cell
      receptor interaction with the major histocompatibility complex plus peptide
      complex on the surface of antigen-presenting cells, and have highlighted the
      pivotal role of the peptide in determining the subsequent T cell response. There
      has therefore been increased interest in the use of synthetic peptides to alter T
      cell responses to foreign antigens. The purpose of this review is to highlight
      the recent studies which demonstrate the potential immunomodulatory functions of
      peptides derived from major histocompatibility complex molecules.

PMID- 8737863
TI  - Chronic rejection.
AB  - The pathogenesis of chronic rejection is a complex network of immunological,
      metabolic and haemodynamic events leading to a cascade of cellular and molecular
      events with a subsequent remodelling of the graft. Evidence suggests that the
      frequency and intensity of acute rejection episodes strongly correlate with graft
      loss as a result of chronic rejection. The most characteristic feature of chronic
      rejection, shared by all organs, is concentric generalized arteriosclerosis with
      low-grade perivasculitis affecting all intragraft arteries of the transplant. In
      vitro studies have demonstrated that a variety of cells and molecules may
      regulate smooth muscle cell replication in the vascular wall, the migration of
      smooth muscle cells from the media into the intima, and the development of
      arteriosclerotic lesions throughout the entire length of the vessel wall. These
      molecules include peptide growth factors, cytokines, vasoactive hormones, and
      lipid mediators of inflammation (eicosanoids), and they are secreted in situ by
      inflammatory, endothelial and smooth muscle cells in the vascular wall. In order
      to prevent chronic rejection it is necessary to optimize immunosuppression,
      possibly by the use of new immunosuppressive drugs that also seem to have direct
      inhibitory effect on smooth muscle cells and on transplant arteriosclerosis. The
      scope of this review is to highlight our current understanding of the risk
      factors, pathogenesis and prevention of chronic renal allograft rejection. This
      review will also briefly discuss present animal models used to investigate
      chronic rejection at the cellular and molecular level.

PMID- 8737864
TI  - Vasculitis and the kidney.
AB  - This review analyzes the current literature on small vessel vasculitis affecting
      the kidney, and emphasizes the important contribution of anti-neutrophil
      cytoplasmic antibodies to recent advances in understanding. There is a very
      strong correlation between the presence of these auto-antibodies and the types of
      systemic vasculitis that cause crescentic glomerulonephritis with scanty immune
      deposits. Despite this, it is not yet clear whether anti-neutrophil cytoplasmic
      antibodies cause vasculitis or merely reflect its presence. However, the recent
      demonstration of anti-neutrophil cytoplasmic antibodies in spontaneous murine
      models of vasculitis, and the development of a model of vasculitis caused by
      immunity to myeloperoxidase strengthen the case for a pathogenic role. Regardless
      of whether they are pathogenic, sequential measurement of anti-neutrophil
      cytoplasmic antibody titres have proved extremely useful in the management of
      patients with systemic vasculitis. They are a considerable help in diagnosis, but
      perhaps they are even more important as a guide to maintenance immosuppressive
      therapy; relapses are rare when anti-neutrophil cytoplasmic antibodies cannot be
      detected, and are common when their titres are rising. Other ways to minimize
      exposure to cyclophosphamide are also reviewed.

PMID- 8737865
TI  - Genetics of kidney development.
AB  - Genetic approaches have clarified the molecular basis of many different stages of
      kidney development with considerable clarity. By introducing targeted mutations
      in mice, a number o transcription growth factors have been shown to be required
      for early kidney tubulogenesis. Most recently, the transcription factor Pax-2,
      and bone morphogenetic protein-7, a growth factor, were added to the list of
      factors required for the early stages of kidney tubulogenesis. Compared with the
      defects seen in mice lacking Pax-2 or bone morphogenic protein-7, the formation
      of cysts in tubules is morphologically a very mild defect. Cysts are seen in many
      transgenic mice with overexpression of a gene in the kidney, and in some
      'knockout' mice lacking a gene. Some of these genes might be involved in human
      cystic diseases. However, it was recently shown that the gene affected in 85% of
      patients with autosomal dominant polycystic kidney disease encodes a novel
      protein, called polycystin. This protein is very large and has a sequence
      suggesting multiple transmembrane domains. It extracellular domains suggest that
      polycystin is involved in cell-cell and cell-matrix interactions.

PMID- 8737866
TI  - Epidemiology and prevention.

PMID- 8737867
TI  - Renal immunology and pathology.

PMID- 8737868
TI  - Botryomycosis.

PMID- 8737869
TI  - Erythema nodosum leprosum.

PMID- 8737870
TI  - Infection with Penicillium marneffei.

PMID- 8737871
TI  - Adult T-cell leukemia/lymphoma cutaneous type.

PMID- 8737872
TI  - Porokeratosis of Mibelli and HIV-infection.
AB  - BACKGROUND: The exacerbation of porokeratosis of Mibelli associated with
      inmunosuppression has been well documented. MATERIALS AND METHODS: We describe
      the clinical and histologic data of three cases of HIV-infected patients, who
      developed porokeratosis following HIV-contact. RESULTS: The three reported
      patients were found to have the clinical and histologic features of porokeratosis
      of Mibelli. Either the exacerbation or development of the disease followed HIV
      infection. CONCLUSION: Although porokeratosis is not a disease indicative of
      AIDS, its flare-up or its presence in HIV-infected patients may serve as a marker
      of inmunodeficiency.

PMID- 8737873
TI  - Skin diseases among adolescent boys in Abha, Saudi Arabia.
AB  - BACKGROUND: Adolescence is characterized by a sensitivity to issues of
      attractiveness. With dermatologic conditions, this may adversely affect early
      detection and compliance. METHODS: A cross-sectional study was carried out on a
      multistage stratified random sample of 647 adolescent schoolboys in Abha, Saudi
      Arabia, to determine the prevalence of skin diseases. The age of the boys ranged
      from 11 to 19 years with an average of 15.3 +/- 1.9 years. RESULTS: It was found
      that 19.8% of the children were affected by one form or another of transmissible
      skin diseases (TSD). The most common types were: pediculosis capitis (9.6%),
      verruca vulgaris (3.9%), and tinea pedis (1.9%). The prevalence of TSD increased
      significantly as the age decreased and as the crowding index increased. As for
      non-transmissible skin diseases, acne vulgaris was the most prevalent disease
      (56.3%). The prevalence and severity of acne increased significantly as the age
      increased. CONCLUSIONS: The findings indicate the need to develop regional
      intervention programs at the school level. Appropriate continuing medical
      education programs for school health workers in the region are mandatory to
      achieve this goal.

PMID- 8737874
TI  - Cutaneous manifestations of systemic lupus erythematosus: study from Lahore,
      Pakistan.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder in which
      cutaneous lesions occur in 85% of patients. This study from Lahore, Pakistan, was
      conducted to determine the pattern and incidence of such lesions in SLE. METHODS:
      Forty patients with SLE fulfilling the clinical and laboratory criteria of the
      American Rheumatism Association (ARA) (1982) were examined between October 1992
      and September 1993 for the presence of cutaneous manifestations. RESULTS: Skin
      changes noted were: noncicatricial diffuse alopecia (82.5%), malar rash (60%),
      mucosal lesions (60%), discoid eruption (57.5%), photosensitivity (60%), nail
      involvement (55%), vascular lesions (50%), pruritus (45%), and pigmentary changes
      (37.5%). Peripheral gangrene, chronic ulcers, Raynaud's phenomenon, urticaria,
      chilblains, thrombophlebitis, palmar erythema, and erythema multiforme were rare.
      Antinuclear antibody reaction was positive in 80% and anti-dSDNA antibodies in
      70%. CONCLUSION: A different clinical pattern was noted in our patients than
      reported previously.

PMID- 8737875
TI  - Recurrent nonmelanoma skin cancer in southern Australia.
AB  - BACKGROUND AND OBJECTIVE: In retrospective studies of non-melanoma skin cancers,
      the recurrence rates were relatively high. This study had as its aim to determine
      the recurrence rate of nonmelanoma skin cancer (NMSC) and prospectively, risk
      factors for recurrence in southern Australia. STUDY DESIGN: This is a prospective
      study of outpatients with histologically confirmed NMSC. All patients seen by a
      dermatologist between November 1988 and November 1989 were entered into the study
      and followed for at least 3 years. Any recurrent NMSCS were removed and recorded.
      RESULTS: Four hundred and eighty-one patients were entered and 420 followed for
      at least 3 years. A recurrent NMSC developed in 8% (adjusted for losses). A
      multivariate analysis determined that the main risk factor for recurrence within
      the first 3 years of follow-up was the number of NMSC a patient had when entering
      into the study. Those with 3 to nine NMSC were five times more likely to develop
      a recurrence than those with less than three NMSC. Those with 10 or more NMSC
      were 25 times more likely to develop a recurrence. Age, sex, and types of skin
      cancers removed were not risk factors within the first 3 years of follow-up.
      CONCLUSION: Patients who have had multiple skin cancers require careful follow-up
      because of the risk of developing recurrences.

PMID- 8737876
TI  - Treatment of actinic prurigo in Chimila Indians.
AB  - BACKGROUND: Actinic prurigo has a high prevalence in women of child-bearing age.
      Its treatment has been, among others, with thalidomide. To avoid the deleterious
      effects of this drug on the embryo, therapeutic alternatives have been sought.
      Among these, tetracycline and vitamin E have been investigated as to their
      influence on the symptoms of actinic prurigo. Both these drugs affect superoxide
      radicals that are thought to be involved in the pathogenesis of actinic prurigo.
      MATERIALS AND METHODS: Patients (Chimila Indians with a high prevalence of
      actinic prurigo) received either (a) tetracycline, 500 mg three times daily, for
      6 months, or (b) vitamin E, 100 IU daily, for 6 months. The patients were seen
      once monthly. There were eight patients in each group. RESULTS: Both drugs used
      were effective. Pruritus was remarkably improved by either treatment. None of the
      side effects were severe enough to lead to interruption of treatment, but the
      observation period posttreatment was relatively short, 4 months for tetracycline
      and 2 months for vitamin E. The improvement occurred in spite of the continuation
      of extensive exposure to the sun. CONCLUSIONS: Tetracycline and vitamin E are
      efficacious in relieving the pruritus of actinic prurigo. Preliminary trials of a
      combination treatment with these two drugs is a new avenue which has shown in
      preliminary trials to yield synergistic effects which might allow the dosage of
      tetracycline to be reduced.

PMID- 8737877
TI  - Corneocytes in scaly parakeratotic diseases.
AB  - BACKGROUND AND OBJECTIVES: The stratum corneum of some of the scaly
      (parakeratotic) diseases was examined with light and scanning electron microscopy
      (SEM) with the purpose to reveal the importance of this layer in the diagnosis of
      some of the diseases associated with the formation of scales. MATERIALS AND
      METHODS: Two biopsies of the skin surface were taken: one, obtained from 80
      patients with various parakeratotic scaly diseases and from 25 control subjects,
      was processed for light microscopy; the other biopsy for SEM was taken from 10
      control subjects and 25 patients. The diagnoses of these patients were: psoriasis
      (5 patients), erythrodermic psoriasis (2 subjects), parapsoriasis (5 patients),
      pityriasis rubra pilaris (5 subjects), pityriasis rosea (3 subjects), and
      seborrheic dermatitis (5 subjects). RESULTS: The light microscopic studies showed
      that normal corneocytes are of polygonal shape with their largest diameter
      measuring 42 microns; these cells lacked nuclei. All parakeratotic cells appeared
      bizarre in shape, smaller than normal, and the cells contained a nucleus. With
      SEM, normal cells appeared relatively regular in size and shape, trabeculated,
      and had a flat surface. Cells examined in all the diseases revealed various
      sizes, outlines, and trabeculae. Specific surface patterns (print) of diseased
      cells were: "fish-scale" in psoriasis; "marbled" in parapsoriasis, "rocky stone"
      in pityriasis rubra pilaris; "heart-shaped" in seborrheic dermatitis, and
      semicrystalloid in pityriasis rosea. CONCLUSIONS: Parakeratosis is characterized
      not only by the retention of the nucleus in keratinocytes, but is also
      characterized by a cell of smaller size. The specific print of a disease helps in
      the diagnosis. The print will change with different stages of a disease.

PMID- 8737878
TI  - Lethal epidermolysis bullosa in black South African neonates.
AB  - BACKGROUND: While there have been a number of reports of epidermolysis bullosa
      (EB) occurring in South African black neonates, the disorder occurs rarely and
      the electron-microscopic findings in affected South African patients have not
      been documented previously. METHODS: All patients with neonatal EB who were
      biopsied for electron microscopy at the South African Institute for Medical
      Research between 1986 and 1992 were included in the study. The eight boys and
      three girls had extensive blistering and all died within the first few months of
      life. RESULTS: Nine of the patients showed the features of junctional EB, whereas
      the remaining two were classified as dystrophic EB. There were no differences in
      the clinical manifestations between the two categories. CONCLUSIONS: The lethal
      form of EB in South African black neonates is associated with at least two types
      of basement membrane defect.

PMID- 8737879
TI  - Detection of T lymphocytes and T lymphocyte subsets in lichen planus: in situ and
      in peripheral blood.
AB  - BACKGROUND: Abnormal immune mechanisms are thought to be important in the
      pathogenesis of lichen planus (LP). This is a study to clarify the changes that
      occur in T lymphocytes and T lymphocyte subsets, both in situ and in peripheral
      blood. METHODS: A group of 100 patients with LP were included in this study. T
      lymphocytes and T lymphocyte subsets were detected in lesional skin by
      immunoperoxidase cell surface staining using monoclonal antibodies. Peripheral T
      lymphocytes and T lymphocyte subsets were also detected by indirect
      immunofluorescence using monoclonal antibodies. A group of 10 normal healthy
      subjects were used as controls. RESULTS: The study of the lesional T lymphocytes
      and T lymphocyte subsets demonstrated that helper T cells was the predominant
      subset in LP lesions in most of the patients. This predominance was evident
      irrespective of the duration of the disease and was more evident in late than in
      early lesions. The percentage of both total T lymphocytes and helper T cells in
      peripheral blood was decreased significantly in patients compared with controls.
      A significant decrease in helper T cells and the helper/cytotoxic T cell ratio
      was detected in patients with a longer duration of the disease. CONCLUSION:
      Activation of helper T lymphocytes that were found to be the predominant subsets
      in LP lesions may be responsible for epidermotropic cellular infiltrates leading
      to damage and destruction of epidermal cells.

PMID- 8737880
TI  - Bibliography of secondary sources on the history of dermatology. I. Journal
      articles in English supplemented through 1995.

PMID- 8737881
TI  - Anergic cutaneous leishmaniasis versus lobomycosis.

PMID- 8737882
TI  - Giant cutaneous rhinosporidiosis.

PMID- 8737883
TI  - Tuberculosis cutis orificialis.

PMID- 8737884
TI  - Segmental neurofibromatosis with ipsilateral renal agenesis.

PMID- 8737885
TI  - Oil of bitter orange: new topical antifungal agent.
AB  - BACKGROUND: Superficial dermatophyte infection is one of the most common
      dermatologic diseases. Some of these infections are extremely resistant to
      therapy. METHODS AND PATIENTS: Sixty patients participated in this study; they
      were classified into three groups (20 patients in each). All groups had
      comparable numbers of patients with tinea corporis, cruris, and pedis. Group 1
      was treated with a 25% emulsion of oil of bitter orange (OBO) three times daily;
      group 2 was treated with 20% OBO in alcohol three times daily and group 3 was
      treated with pure OBO, once daily. Clinical and mycologic examinations were
      performed before therapy and every week until a complete cure had occurred.
      RESULTS: In group 1, 80% of patients were cured in 1 to 2 weeks and 20% in 2 to 3
      weeks. In group 2, 50% were cured in 1 to 2 weeks, 30% in 2 to 3 weeks and 20% in
      3 to 4 weeks. In group 3, 25% of patients did not continue the trial. Of the
      remaining patients, 33.3% were cured in one week, 60% in 1 to 2 weeks, and 6.7%
      in 2 to 3 weeks. Oil of bitter orange produced no side effects except mild
      irritation seen with the use of the pure form. CONCLUSIONS: An in vitro study
      showed that OBO (natural product) exerts fungistatic and fungicidal activity
      against a variety of pathogenic dermatophyte species. It is a promising, cheap,
      and available topical antifungal therapeutic agent.

PMID- 8737886
TI  - Utility of bone marrow and liver biopsies for staging cutaneous T-cell lymphoma.
AB  - BACKGROUND: The wide use of staging procedures, looking for visceral involvement
      in patients with cutaneous T-cell lymphoma (CTCL), is controversial, especially
      in the early stages. In this study, we analyzed the results of bone marrow biopsy
      and laparoscopy with liver biopsy in a series of 43 patients with CTCL. METHODS:
      Clinicopathologic stages were established by a modification of the TNM system
      proposed in 1979. Results of staging procedures were correlated with blood cell
      counts and laboratory tests. The usefulness of the staging procedures was
      analyzed particularly in patients without clinical or biologic evidence of
      extracutaneous disease. RESULTS: The patient's median age was 66 years; 35
      patients were men and eight women. The clinicopathologic stages were as follows:
      T1: 3 cases; T2: 15; T3: 14; T4: 11; N0: 15; N1: 28; M0: 38; M1: 5; B0: 37; and
      B1: 6 cases. Internal lymph node disease, diagnosed by lymphangiography and/or
      abdominal scanning, was demonstrated in 37% of patients. Bone marrow infiltration
      was seen in 12% of patients and was the only form of visceral involvement. All
      liver biopsies were negative. Serum lactate dehydrogenase (LDH) levels were
      raised in patients with lymph node disease; it was the only laboratory test that
      correlated with extracutaneous involvement. Staging procedures changed three of
      the nine patients with a clinical T1-T2N0M0B0 stage (33%) to a more advanced
      stage. The abdominal lymph node evaluation allowed a reclassification from N0 to
      N1 in two of nine cases (22%); one of the remaining cases was reclassified from
      M0 to M1 on the basis of bone marrow biopsy results. CONCLUSIONS: Our results
      indicate that bone marrow biopsy is a useful investigational procedure for
      determining extracutaneous disease in CTCL. Peritoneoscopy with liver biopsy
      rarely is informative; however, as our study does not include a very large number
      of patients, these preliminary conclusions must be confirmed in the future by
      including more cases.

PMID- 8737887
TI  - Resolution of generalized granuloma annulare with isotretinoin therapy.

PMID- 8737888
TI  - Neural activity in the VMH associated with suppression of the circulatory system
      in rats.
AB  - Spontaneous neural activity within the ventromedial nucleus of the hypothalamus
      (VMH) was monitored in rats to search for neurons regulating the autonomic
      nervous system. By means of multiple unit activity (MUA) recording method, unique
      explosive rises in neural activity (MUA volleys), 1 to 4 min in duration, were
      recorded in conscious freely moving animals. Heart rate was monitored as an
      autonomic parameter and found to decrease when MUA volleys appeared. These MUA
      volleys also occurred under urethane anesthesia, and blood pressure and heart
      rate decreased simultaneously with the volleys, but body temperature remained
      constant. This fall in blood pressure (but not heart rate) was replicated by
      electrical stimulation through the electrodes that recorded MUA volleys,
      suggesting that the neurons responsible for MUA volleys can suppress the
      circulatory system. The frequency of MUA volleys exhibited a clear diurnal
      variation: they appeared every 15 or 30 min in the light phase but only seldom in
      the dark. This diurnal variation seems to be an endogenous circadian rhythm
      because it was indicated to freerun after blinding the animals. These results
      suggest that there is a discrete population of neurons in the VMH that fires
      predominantly during the light phase in an episodic manner and suppresses the
      circulatory system.

PMID- 8737889
TI  - Analgesic effect of ceruletide in men is limited to specific pain qualities.
AB  - Cholecystokinin (CCK) and related peptides are supposed to be potent analgesic
      neuropeptides. Studies in rodents suggest a dose-dependent biphasic effect. The
      present study aimed to examine the pain modulating effect of different doses (0.5
      microgram and 5 micrograms) of ceruletide (CRL), infused i.v. for 30 min. Pain
      thresholds were obtained for ischemic, mechanical, and thermal pain. In addition,
      pain tolerance was measured for mechanical pain. According to a placebo
      controlled double-blind within-subject design 25 healthy men attended three
      experimental sessions each. Pain perception was measured as a baseline and twice
      after the infusion. The effect of both doses of CRL to enhance the pain threshold
      for thermal stimuli is in line with former studies. However, perception of heat
      stimuli above or below the threshold was not substantially affected by CRL
      treatment. Algesic properties of CRL are also indicated, because the tolerance
      for mechanical pain decreased after administration of the high dose of CRL.
      Perception of ischemic pain was not obviously influenced by any of the
      treatments. The role of CRL in human pain modulation seems to vary, depending on
      the type of experimental pain.

PMID- 8737890
TI  - Refeeding after prolonged fasting in rats: nycthemeral variations in dietary self
      selection.
AB  - The influence of metabolic status on food selection during refeeding after
      fasting was investigated in rats fasted for a long period of time and
      subsequently given the choice of eating fat, protein, and carbohydrate
      individually. Rats were fasted until either metabolic phase 2 (essentially using
      lipids) or metabolic phase 3 (when there was a rise in protein utilization). The
      very large first meal of the refeeding was identical in the two groups of animals
      and consisted mainly of fat and protein. The observed diurnal hyperphagia
      persisted for 2 days in phase 2, while in phase 3 the hyperphagia persisted
      throughout the 8 observation days. Both periods of hyperphagia consisted of an
      increase in fat and in protein intakes. The nocturnal intake was increased, but
      to a lesser extent, on days 4 and 5 in phase 2 and on days 4, 5, and 6 in phase
      3. These results can be related to the metabolic events present during the
      diurnal part of the nycthemeral cycle.

PMID- 8737892
TI  - Adult rat vigilance states discrimination by artificial neural networks using a
      single EEG channel.
AB  - Two multilayer neural networks were designed to discriminate vigilance states
      (waking, paradoxical sleep, and non-REM sleep) in the rat using a single parieto
      occipital EEG derivation. After filtering (bandwidth 3.18-25 Hz) and digitization
      at 512 HZ, the EEG signal was segmented into eight second epochs. Five variables
      (three statistical, two temporal) were extracted from each epoch. The first
      network computed an epoch by epoch classification, while the second network also
      utilized contextual information from contiguous epochs. A specific postprocessing
      procedure was developed to enhance the vigilance state discrimination of the
      neural networks designed and especially paradoxical sleep state estimation. The
      classifications made by the networks (with or without the postprocessing
      procedure) for six rats were compared to these made by two human experts using
      EMG and EEG informations on 63,000 epochs. High rates of agreement (> 90%)
      between humans and neural networks classifications were obtained. In view of its
      development possibilities and its applicability to other signals, this method
      could prove of value in biomedical research.

PMID- 8737891
TI  - Daylength and body mass affect diet self-selection by Siberian hamsters.
AB  - Siberian hamsters exhibit a decrease in peak body mass/fat and caloric intake
      when they are exposed to short winter-like days (SDs) compared with hamsters
      exposed to long summer-like days (LDs). We hypothesize that the photoperiod may
      directly or indirectly mediate alterations in gustatory processing that may
      account for shifts in the preferences for specific food types and/or
      macronutrients. Two experiments lasting 14 days each were conducted to: 1)
      identify photoperiod-related differences in diet selection, and; 2) determine
      whether these differences were a primary effect of SD exposure or a secondary
      effect due to SD-induced decreases in body fat/mass. In Experiment 1, two groups
      of hamsters were exposed to either LDs or SDs and given access to three complex
      food types [sunflower seeds (SF); rabbit chow (RC); millet seeds (M)]. In
      addition to their photoperiod-induced decreased body and fat pad mass, and
      caloric intake, SD-housed hamsters exhibited significant differences in their
      patterns of diet selection and relative amounts of fat, carbohydrate (COH), and
      protein eaten compared with LD-housed hamsters. By the end of the experiment, SD
      housed hamsters selected a diet higher in COH and protein and lower in fat than
      that selected by LD-housed hamsters. Because SD-housed hamsters decrease their
      body mass/fat, this may reflect an adaptive strategy to maintain a leaner body
      mass. A second experiment was conducted to test whether the diet selection
      pattern of SD-housed hamsters was due to the SD-induced decrease in body
      mass/fat. LD-housed hamsters were allowed to feed ad lib (AL group), or were food
      restricted (FR group) to simulate a SD-induced decrease in body mass. Both groups
      were then released into the diet self-selection paradigm. FR hamsters reversed
      their food restriction-induced decrease in body mass and showed concurrent
      alterations in diet self-selection patterns that were distinct from the SD
      induced patterns seen in Experiment 1. Specifically, they showed a persistent
      hyperphagia and selected a larger proportion of their total calories as M (high
      COH) and less as SF (high fat) than did AL hamsters during their return to LD
      body mass levels. However, once LD body mass levels were achieved, they increased
      their SF intake, and thus fat consumption. Despite these dynamic daily changes,
      the average selection patterns of both the diet types and macronutrients were not
      different by the end of the experiment. Therefore, it appears that the SD-induced
      changes in the selection of food sources (and ultimately, the macronutrient
      composition of the diet) cannot be solely attributable to the SD-induced
      decreases in body mass.

PMID- 8737893
TI  - Effect of feeding time on hepatic nucleic acid, plasma T3, T4, and GH
      concentrations in rainbow trout.
AB  - The effect of feeding time (dawn, midnight) on the growth performance and daily
      pattern of liver nucleic acid concentrations, plasma thyroid hormone, and growth
      hormone concentrations was studied in immature rainbow trout (Oncorhynchus
      mykiss, mean individual weight: 55 g). Fish were held in groups of 20 individuals
      (12 groups per treatment) and maintained in flow-through tanks supplied with
      river water under natural photoperiod. Food pellets (Aqualim, 49% crude protein)
      were delivered daily over a 30-min period by means of belt feeders. Growth
      performance and protein retention efficiency were higher for trout fed at dawn
      than for those fed at midnight, whereas both groups of fish ingested the same
      total amount of feed. All parameters studied showed significant daily variations.
      The daily patterns of liver RNA concentrations, RNA/DNA, and protein/DNA ratios
      were significantly different between fish fed at dawn and at midnight, indicative
      of a higher liver protein synthesis in the trout fed at dawn. On average, plasma
      thyroid hormone levels were higher and plasma GH concentrations were lower in
      trout fed at dawn compared with those fed at midnight. The hormonal patterns were
      only affected by feeding time when the fish were fed at dawn. These results
      suggested that the observed differences in growth and protein retention
      efficiency were linked to the observed differences in plasma hormone levels.

PMID- 8737894
TI  - Influences of fat, energy, and time of day on mood and performance.
AB  - Paired studies testing the effects of lower energy high-fat, low-CHO meals (3181
      kJ, fat:CHO energy ratio 54:41) and higher energy low-fat, high-CHO meals (3599
      kJ, fat:CHO energy ratio 7:88) were conducted in 18 healthy males. The meals were
      eaten at 1030 h by group A (nine subjects) and 1230 h by group B (nine subjects).
      Subjective lassitude increased following ingestion of all four meals, but there
      was little change in performance. In addition, group A, but not group B, felt
      significantly less vigorous, imaginative, and antagonistic, and significantly
      more dreamy, feeble, and fatigued after the lower energy high-fat, low-CHO meal
      than after the higher energy low-fat, high-CHO meal. These results suggest that
      in the morning, fat exerts a greater depression on alertness and mood than
      carbohydrate irrespective of a reduction in energy content, but this effect
      varies according to the time at which food is eaten, and is less evident at lunch
      time.

PMID- 8737895
TI  - The relevance of continuous blood pressure monitoring in examining the
      relationship of memory efficiency with blood pressure characteristics.
AB  - The study of the relationship between hypertension and cognitive decline is
      characterized by various difficulties of realization and, as a consequence, by
      incongruent results. One of the reasons for these difficulties may be explained
      by the occasional method of measurement of blood pressure (once a day). This
      study presents the results obtained in 27 normotensive and mild hypertensive
      subjects of both sexes (ages between 20 and 77 years) with a continuous blood
      pressure monitoring for 24 h. A noninvasive sphygmomanometric technique was used
      employing a portable recorder programmed to take a measure every 30 min. Both
      objective and subjective measures of memory, measures of attention efficiency,
      and IQ were correlated to the blood pressure measures. Continuous monitoring data
      of blood pressure were analyzed according to a model that included a macroscopic
      descriptive analysis, a microscopic rhythmometric analysis, and a microscopic
      integrative analyses where the effects of the interaction between level and
      duration of excess and the time of the day when the excess eventually appeared
      were considered. Results evidenced no differences in cognitive efficiency between
      those subjects identified with the traditional occasional measurement of blood
      pressure as hypertensives of mild severity and the normal subjects. Cognitive
      efficiency of our subjects was found correlated, independently from the clinical
      diagnosis, with the time of peak and with the duration of excess of their blood
      pressure when the results of the analyses on the continuous monitoring of blood
      pressure were considered.

PMID- 8737896
TI  - Sensitivity to testosterone varies with strain, sex, and site of action in
      chickens.
AB  - Day-old chicks (cockerels and pullets) of two strains of chicken (a commercial
      breed and strain of feral fowl) were treated intramuscularly with 25 mg/0.1 ml of
      testosterone oenanthate on day 1 posthatching. Controls received 0.1 ml of the
      vehicle. Attack and copulatory behavior were scored from days 7 to 14 using
      standard hand-thrust tests, which rank the responses from 1 to 10. The sizes of
      the comb and testes were also measured. All measures showed strain and sex
      differences. Copulation and attack scores were highest in males of the feral
      strain. Even untreated males of the feral strain had high scores, and these were
      further elevated by the testosterone treatment. In fact, the attack scores of
      feral males were marginally higher than those of the males of the commercial
      strain treated with testosterone. Testosterone treatment of the feral females
      also elevated attack and copulation to a much greater extent than in the
      commercial strain. Opposite effects occurred for the development of the comb.
      Comb volume, absolute and adjusted for body weight, was much greater in treated
      chicks of the commercial strain than in those of the feral strain. These results
      indicate that chicks of the feral strain may have more central and fewer
      peripheral receptors for testosterone or that their receptors for testosterone
      are more sensitive than those of the commercial strain. Alternatively, there may
      be strain, as well as sex, differences in the metabolism of testosterone.

PMID- 8737897
TI  - Modulation of the baroreceptor reflex by stimulation of the hypothalamic defense
      and vigilance areas.
AB  - Electrical stimulation of the hypothalamic defense area (HDA) elicits a
      pressor/tachycardia response that is believed to prepare an animal for fight or
      flight. In contrast, electrical stimulation of the hypothalamic vigilance area
      (HVA) evokes a pressor/bradycardia response that is associated with the
      inhibition of movement. The differences in the behavioral components of these two
      affective response patterns suggest differential modulation of the baroreceptor
      reflex. The present study tested this idea by assessing the effects of electrical
      stimulation of the HDA and the HVA upon the bradycardia/depressor response
      elicited by stimulation of the aortic nerve (AN) in rabbits. Concurrent HDA and
      AN stimulation was observed to attenuate the AN-elicited bradycardia but enhanced
      the depressor response elicited by AN stimulation. In contrast, concurrent
      stimulation of the HVA and AN enhanced the bradycardia elicited by AN stimulation
      but reduced the magnitude of the AN-elicited depressor response. These results
      provide evidence for differential modulation of the baroreceptor reflex during
      the defense and vigilance reactions.

PMID- 8737898
TI  - Chronic tryptophan restriction disrupts grooming chain completion in the rat.
AB  - Tryptophan restriction in the diet leads to low levels of brain serotonin.
      Serotonin has been implicated in the magnitude of novelty-induced grooming
      behavior, but its possible role in self-grooming chain completion has not been
      investigated. A tryptophan-deficient diet produced fewer chain-associated face
      washings, more face washings alone, fewer number of chains, as well as elementary
      units into chains. Thereafter, an apparent lower threshold for emotional
      responsiveness also took place. Impairments of the serotoninergic inhibitory
      activity of striatal and/or nigral dopaminergic terminals is suggested, because
      corpus striatum has been proposed to be an organizer structure of both the serial
      ordering as well as in the completion of the self-grooming chains.

PMID- 8737899
TI  - Pavlovian conditioning of LPS-induced responses: effects on corticosterone,
      splenic NE, and IL-2 production.
AB  - The present study used a taste aversion paradigm to condition lipopolysaccharide
      (LPS)-induced suppression of splenic lymphocyte interleukin-2 (IL-2) production,
      with concurrent measurement of corticosterone production and splenic
      norepinephrine (NE) content). In training, two groups of rats received saccharin
      and IP LPS in a paired (P) manner and a third group in a specifically unpaired
      (U) manner. In the test, the unpaired group (group U) and one of the paired
      (group P) groups were re-exposed (R) to the cue and the other not (NR). An
      additional group controlled for the effects of cues (conditional stimulus) and
      fluid deprivation (negative control; NC). A robust taste aversion in the P-R
      group was accompanied by suppression of IL-2 production, reduced splenic NE
      content, and elevated corticosterone production, relative to combined controls
      (i.e., groups U-R, P-NR, and NC). The conditioned modulation of IL-2 secretion,
      along with the concomitant alteration of adrenocortical and sympathetic
      mediators, supports the involvement of bidirectional central nervous-immune
      system pathways in this paradigm.

PMID- 8737900
TI  - The effects of chronic corticosterone on memory performance in the platform maze
      task.
AB  - Acquisition and reversal of a memory task dependent on hippocampal integrity were
      assessed in rats following chronic corticosterone treatment. Young adult male
      rats were injected daily with corticosterone (10 mg/kg, SC) for 8 weeks. Memory
      was assessed during the last week of treatment with an elevated platform maze.
      During acquisition trials, corticosterone-treated rats did not differ from
      vehicle-treated controls in either the location of first hole chosen nor in the
      latency to locate the escape hole. In the reversal trials, when the position of
      the escape hole was rotated 135 degrees, both groups successfully reversed their
      responses without persevering towards the previously rewarded escape hole
      location. These findings suggest that, despite the probability of corticosterone
      induced changes in hippocampal physiology, chronic corticosterone treatment does
      not adversely affect performance in a memory task dependent on hippocampal
      integrity.

PMID- 8737901
TI  - Dissociation between adrenal tyrosinehydroxylase and phenylethanolamine N
      methyltransferase activities following repeated experience of defeats in
      individually housed male DBA/2J mice.
AB  - Adrenal activities of tyrosinehydroxylase (TH) and phenylethanolamine N
      methyltransferase (PNMT) were compared between individually housed defeated
      intruders and socially housed residents (SR) (Experiment 1), and between
      individually housed defeated intruders and individually housed victor residents
      (Experiment 2). In addition, corticosterone titers were determined and dominance
      status of SR (dominant, subdominant active, and subdominant passive) considered.
      Defeats were induced twice a week for 6 consecutive weeks in short resident
      intruder encounters. The main findings were: 1) within the groups of SR, TH and
      PNMT activities were high in dominant and low in subdominant-passive mice; 2) in
      Experiment 1, TH activities of individually housed defeated intruders were low
      like those of subdominant-passive SR whereas their PNMT activities were high like
      those of dominant SR; 3) in Experiment 2, TH activities were low in both
      categories of individually kept mice whereas PNMT activities were significantly
      elevated in the defeated intruders; 4) in both experiments, PNMT activities of
      intruders correlated significantly with the accumulated number of attacks they
      had received throughout all resident-intruder tests. Findings show separate
      effects of permanent social stimulation and of episodic experience of defeats on
      adrenal catecholamine synthesis. Lack of permanent social stimulation decreased
      adrenal TH and PNMT activities whereas repeated episodic experience of defeats
      specifically increased PNMT but not TH activities in individually housed mice.

PMID- 8737902
TI  - Modifications in dietary self-selection specifically attributable to voluntary
      wheel running and exercise training in the rat.
AB  - To explore the effects of physical exercise on total caloric intake, body weight
      gain, and dietary self-selection in rats, female rats of the Dark Agouti strain
      were placed on macronutrient self-selection. They had free access to running
      wheels during the whole experimental period. After 16 days of voluntary exercise
      only, they were trained on a motor-driven treadmill (16 m/min) at the beginning
      of the dark period. Runtime was progressively increased and reached 3 h per day
      (plateau). When trained, the rats decreased spontaneous wheel running. Voluntary
      wheel running did not modify body weight gain. However, it increased both
      carbohydrate and total caloric intakes. Exercise training reduced body weight
      gain, but did not further modify total caloric intake. Moreover it increased
      protein and reduced fat intakes. Most of the training-induced modifications were
      not side effects of fasting during exercise training.

PMID- 8737903
TI  - d-fenfluramine's effects on normal ingestion assessed with taste reactivity
      measures.
AB  - The effects of d-fenfluramine on intake and on hedonic responses to taste stimuli
      in rats were investigated using a modified taste reactivity paradigm. Subjects (n
      = 15) were first trained to consume a 3% sucrose solution. They were then
      pretreated with d-fenfluramine (0.3-3.0 mg/kg, i.p.), and tested with access to
      either 3% sucrose, or a 0.01% quinine HCl solution. In the modified taste
      reactivity test, chronic oral cannulation was not used; instead, taste reactivity
      measures were scored during periods of noningestion in a voluntary intake test. d
      Fenfluramine reliably reduced both sucrose and quinine consumption, and increased
      latency to drink at the highest dose. d-Fenfluramine also spared aversive
      responses to quinine, but reduced positive ingestive responses to sucrose. These
      results are consistent with an effect of d-fenfluramine to reduce taste
      palatability, which may, in turn, be an important factor in the effect of this
      drug on feeding motivation.

PMID- 8737904
TI  - Drinking and blood pressure responses to central injection of L-NAME in conscious
      rats.
AB  - The drinking behavior and blood pressure responses to i.c.v. administration of
      artificial cerebrospinal fluid (aCSF) or NG-nitro-L-arginine methyl ester (L
      NAME, 10, 250, or 500 micrograms), an inhibitor of nitric oxide synthase, were
      examined in conscious rats following either osmotic stimulation (1.0 M NaCl, 15
      ml/kg, s.c.) or induction of hemorrhage (0.7 ml/min to a 20% blood volume loss).
      Water intake increased in all animals. L-NAME at doses of 250 and 500 micrograms,
      but not 10 micrograms, significantly attenuated water consumption induced by both
      stimuli. The mean arterial blood pressure (MABP), which increased after osmotic
      stimulation, was maintained at pressor levels by 250 and 500 micrograms of L
      NAME, but decreased progressively and reached basal levels after treatment with
      aCSF and the lowest dose of L-NAME (i.e., 10 micrograms). Hemorrhage
      significantly decreased MABP in all rats. The fall in blood pressure associated
      with hemorrhage returned to control levels in animals treated with 250 and 500
      micrograms of L-NAME but not in those treated with aCSF or 10 micrograms of L
      NAME. These results indicate that nitric oxide is involved in the regulation of
      drinking behavior and may play an important role in the central control of blood
      pressure during osmotic stimulation and hypotensive hemorrhage.

PMID- 8737905
TI  - Galanin microinjected into the medial preoptic nucleus facilitates female- and
      male-typical sexual behaviors in the female rat.
AB  - Galanin (GAL) microinjected within the sexually dimorphic medial preoptic nucleus
      (MPN) facilitates male-typical sexual behaviors in the male rat, a response that
      requires the presence of testosterone. As in the male, GAL-immunoreactive cells
      located within the MPN of the female also concentrate gonadal steroids and become
      less immunoreactive after gonadectomy. Thus, to investigate sexual behaviors in
      the female and to determine whether effects are comparable to those obtained in
      the male, GAL was microinjected unilaterally within the MPN of female rats. We
      report that GAL stimulated female-typical lordosis behavior after estrogen
      priming, and that the effect was not due to general arousal as measured by
      nonspecific locomotor activities. In a separate experiment, GAL microinjected
      within the MPN dose-responsively increased mount frequencies and decreased mount
      latencies in testosterone-primed females. A higher dose of testosterone was
      required in females for this stimulation of male-typical sexual behavior than
      required in a previous experiment in males.

PMID- 8737906
TI  - Rewarding electrical brain stimulation: similar thresholds for Flinders Sensitive
      Line Hypercholinergic and Flinders Resistant Line Hypocholinergic rats.
AB  - Flinders Sensitive Line hypercholinergic rats, which exhibit augmented
      hypothermic responses to the cholinesterase inhibitor physostigmine and to the
      muscarinic agonist oxotremorine, have been proposed to represent a useful animal
      model for some aspects of human depression. With disturbance of reward processes
      considered to be a core feature of depression, the present studies were designed
      to investigate the neuropharmacology of brain stimulation-reward (BSR) in
      Flinders Sensitive Line (FSL) rats, Flinders Resistant Line (FRL) rats, and
      outbred control Sprague-Dawley rats. All animals were tested in a rate-free,
      current-threshold brain stimulation-reward paradigm, following acute challenges
      with the monoamine reuptake inhibitor cocaine, the dopamine D1 receptor
      antagonist SCH-23390, the cholinergic muscarinic antagonist scopolamine, and the
      serotonin reuptake inhibitor fluoxetine. Baseline BSR thresholds did not differ
      across the three groups. For all groups, cocaine lowered thresholds, SCH-23390
      and scopolamine-elevated thresholds, while fluoxetine had no significant effect.
      Thresholds for the three groups were not differentially affected by
      pharmacological locomotor activity relative to outbred Sprague-Dawley controls.
      These results suggest that both Flinders lines exhibit behavioral differences
      from outbred control rats, but not with regard to reward processes as assessed by
      rewarding electrical stimulation of the lateral hypothalamus.

PMID- 8737907
TI  - Prevention of stereotypy in laboratory mice: effects on stress physiology and
      behaviour.
AB  - According to the coping hypothesis, the adaptive significance of stereotypies in
      barren housing conditions may lie in their potency to attenuate the deleterious
      consequences of chronic stress. Present evidence from experimental studies is
      ambiguous. When Zur:ICR mice were selectively prevented from stereotypic wire
      gnawing at the cage lid, the previous amount of stereotyped behaviour after a
      short-term decrease in activity was compensated by variable active behaviour on
      the cage floor. This change in behaviour was associated with a short-term
      elevation of serum corticosterone concentrations 24 h after stereotypy
      prevention. However, 3 days later corticosterone levels were back at pretreatment
      base levels. Both behavioural and physiological short-term effects were caused by
      the impact of prevention on behavioural organization. They disappeared as soon as
      new habits were established, even though they were not stereotyped. In contrast
      to the predictions of the coping hypothesis, prevention of stereotypy had no
      significant effects on chronic measures of both the sympathetic-adrenal-medullary
      system and the hypothalamus-pituitary-adrenal system. Thus, there is no evidence
      that stereotypic wire gnawing reduces chronic stress in Zur:ICR mice. This
      implies that coping with stress is not a general aspect of cage-induced
      stereotypic behaviour.

PMID- 8737908
TI  - Prenatal effects of parity on behavioral ontogeny in mice.
AB  - In mice, parity and previous experience with pups may influence a mother's
      behavior towards her pups, thus possibly causing postnatal maternal effects on
      the subsequent development of the pups. The present experiment addressed the
      question whether parity also might have prenatal effects. We studied 622 pups
      from second or third litters that originated from 25 genetically different
      populations and had been fostered to random-bred lactating females. Development
      of responses was significantly delayed in mice from third litters, when compared
      to pups from second litters in three out of five sensorial and four out of eight
      motor tests. In addition, pups from second litters initially were slightly
      heavier than those from third litters. This difference in body weight disappeared
      after the 10th day postnatally. However, it should be noted that effect sizes
      were quite small.

PMID- 8737909
TI  - Illumination has no effect on rats' behavior in the elevated plus-maze.
AB  - Male Wistar rats Shoe:Wist(Shoe) were tested in the elevated plus-maze under
      three different illumination levels (30, 300, and 900 lx). It was found that
      illumination did not change percentage of time spent in closed arms, number of
      closed arm entries, or time spent on open arms, or total arm entry. This confirms
      earlier findings that rat's behavior in the elevated plus-maze is independent of
      light levels.

PMID- 8737910
TI  - A contact eatometer suitable for feeding restriction schedules.
AB  - We describe and test a programmable feeding system based on a contact eatometer,
      previously developed in our laboratory, consisting of a swinging grid beneath a
      hopper that is moved by the rat each time it wants to eat. This has not been
      connected to a solenoid that can block the movement of the grid to prevent access
      to the food. It also provides a continuous record of food approaches even during
      restricted periods when no food is made available, and so it is useful in
      studying the synchronizing role of food in the circadian rhythms of feeding
      behavior. The simplicity and cheapness of its construction and the effective
      blocking of access to food make it an ideal tool in chronobiological studies
      involving the simultaneous use over long periods of a large number of animals.

PMID- 8737911
TI  - The role of olfaction in oil preference in the chicken.
AB  - The role of olfaction on the preference of diets containing 20% medium-chain
      (MCT) or long-chain triacylglycerol (LCT) was investigated in the chicken.
      Olfactory bulbectomized, sham-operated (Sham) or intact (Intact) birds were
      offered a choice between LCT or MCT diet and food intake was measured over a
      short time period. Intact and Sham groups showed a significant preference for LCT
      over MCT diet, but olfactory-bulbectomized chickens lost the preference for LCT
      over MCT. The bilateral cutting of the olfactory nerves confirmed the results
      taken in olfactory bulbectomy. It is concluded that olfaction plays a major role
      in the preference of diets containing MCT or LCT in chickens.

PMID- 8737912
TI  - Receiving grooming as a reinforcer for the monkey.
AB  - The present study was intended to evaluate whether receiving grooming, given to a
      monkey by an experimenter, can be used as a positive reinforcer in operant
      conditioning. When the monkey touched the surface of the correct pattern in a
      visual discrimination task after a tone cue, the experimenter groomed the
      monkey's face, neck, and head with his hand. To test whether the discrimination
      behavior depended on the shape of the stimuli or on the position of the pattern,
      these experimental parameters were changed in the different tasks. When the
      square pattern was assigned as correct and presented on the animal's left side,
      the average score for correct discrimination was 90% in the last 10 sessions out
      of 30 sessions, and this was statistically significant at a confidence level of p
      < 0.005 (Grant's table). Correct discrimination was statistically significant
      when the position of the square was randomly changed to the right and left side
      of the monkey, and also when the correct pattern was reversed from the square to
      the cross and its position was again randomly changed. Therefore, it was
      concluded that the grooming that an experimenter gives to a monkey can be applied
      as a positive reinforcer in operant conditioning. This experimental paradigm is
      considered to be useful for neurophysiological analysis of brain mechanisms
      underlying reward derived from somatosensory input in nonhuman primates.

PMID- 8737913
TI  - Messenger RNA expression of steroidogenesis enzyme subtypes in the human
      pilosebaceous unit.
AB  - In order to define the respective involvement of steroidogenesis enzymes subtypes
      in the control of hair follicle homeostasis, we evaluated, by semiquantitative
      RT/PCR, the expression levels of mRNAs coding for 17 beta-hydroxysteroid
      dehydrogenase type 1 and type 2, 3 beta-hydroxysteroid dehydrogenase, Cyt.P450
      aromatase, steroid 5 alpha-reductase type 1 and type 2 and 11 beta-hydroxysteroid
      dehydrogenase. These assays were performed for several components of the
      pilosebaceous unit (PSU); fresh plucked anagen hairs, sebaceous glands and
      primary culture of dermal papilla, as well as other tissues involved in an active
      steroid metabolism (human testis, liver, placenta, prostate, ovary, uterus and
      adrenals) as controls. We found that plucked hair (i.e. mainly keratinocytes from
      the inner and outer root sheaths) expressed: (1) very high levels of 17 beta
      hydroxysteroid dehydrogenase type 2 corresponding to levels found in liver and
      placenta; (2) high levels of steroid 5-alpha-reductase type 1 corresponding to
      levels found in testis, liver and ovary, and moderate levels of 17 beta
      hydroxysteroid dehydrogenase type 1, which corresponded to the expression in
      testis, prostate and uterus. In contrast, Cyt.P450-aromatase, 3 beta
      hydroxysteroid dehydrogenase and steroid 5 alpha-reductase type 2 were poorly
      expressed in the pilosebaceous unit as compared with other tissues.
      Interestingly, expression patterns of these enzymes in primary cultures of dermal
      papilla were distinctive since 5 alpha-reductase type 1 and 11 beta
      hydroxysteroid dehydrogenase were the only mRNA detected. Taken together, these
      results suggest that not only sebaceous gland but also outer root sheath
      keratinocytes may contribute, through the activity of the steroid 5 alpha
      reductase type 1, to the pathogenesis of androgen-dependent alopecia.

PMID- 8737914
TI  - A minoxidil-related compound lacking a C6 substitution still exhibits strong anti
      lysyl hydroxylase activity in vitro.
AB  - It has been previously reported that minoxidil inhibits the activity of lysyl
      hydroxylase (LH), an enzyme which catalyzes the formation of hydroxylysine, which
      is necessary for proper maturation of collagen at the transcriptional and
      enzymatic levels. Using the reverse transcriptase-polymerase chain reaction, we
      confirmed that this inhibition occurred at least at the transcriptional level.
      Furthermore, we took advantage of this sensitive and rapid method to perform a
      quantitative structure activity relation study using several compounds
      structurally related to minoxidil. We found that when the C6 of the pyrimidinyl
      moiety was substituted, it had to be by a tertiary nitrogen, i.e. an N-piperidin
      ring for the inhibition of LH mRNA synthesis to be observed. Surprisingly,
      however, we found that 2,4-diamino-pyrimidin-3-oxide, a new compound lacking an
      organic moiety para to the nitroxide oxygen, also retained a high inhibitory
      effect on LH mRNA expression, comparable to that of minoxidil. We thus conclude
      that the presence of a substituent para to the nitroxide oxygen is dispensable
      for inhibition of LH mRNA to be observed in vitro. This brings new insights into
      the design of therapeutic agents useful in any condition where an overproduction
      of mature collagen is unwanted, i.e. accelerated wound healing, keloids and
      localized scleroderma.

PMID- 8737915
TI  - A new method for assessing the gloss of human skin.
AB  - A new method for an objective assessment of the gloss of human skin is presented.
      The reflectometric measuring set-up complies with DIN 67530. The principle of
      this new method is based on a contactless determination of the skin's reflection
      of light from a tungsten filament lamp, recorded at an angle of 60 degrees by a
      silicon photocell. In a comparative study with 30 test persons it was discovered
      that the forehead, with 2.70 standardised reflectometer units (RU; SD +/- 0.59
      RU), displayed a significantly higher gloss than the lower arm (1.99 RU, SD 0.28
      RU, p < 0.0001). In an investigation into the influence of four different cream
      bases on the skin gloss it could be determined that the value depends on the
      percentage of grease, the water concentration and the consistency of the
      respective base. The method presented permits a fast, contactless, randomly
      repeatable objective assessment of skin gloss. Since the acceptance of cosmetics
      and pharmaceutical products depends not least on their skin gloss effect, this
      method can provide valuable information when estimating the success of old and
      new products.

PMID- 8737916
TI  - Effect of naftifine on neutrophil adhesion.
AB  - Effective methods of fungal treatment involve reduction in fungal infections and
      host inflammatory responses. Naftifine (NF), a topical antifungal agent, is
      highly active in vitro and in vivo against a wide range of pathogenic fungi.
      Additionally NF has been shown to inhibit polymorphonuclear leukocyte (PMN)
      chemotaxis and respiratory burst activity in an irreversible dose-dependent and
      time-dependent manner. Since leukocyte adherence to endothelia is believed to be
      one of the initial crucial events in the recruitment of circulating leukocytes to
      the site of inflammation, we have investigated the in vitro effect of NF on PMN
      adherence to nylon fiber, BSA-coated glass chamber or polystyrene, and
      endothelial monolayers via three adherence assays. All three assays demonstrated
      a statistically significant reduction (p < 0.01-0.001) in PMN adherence to the
      respective media. In particular, NF (at 30-60 micrograms/ml) significantly
      inhibited PMN adherence to endothelial monolayers (p < 0.01) as measured
      spectrophotometrically by the uptake of rose bengal stain. Therefore, NF inhibits
      PMN adherence to endothelia in our in vitro model system. This inhibition may
      constitute part of the anti-inflammatory effect of NF.

PMID- 8737917
TI  - Radioprotective effects of a protein-free hemodialysate in human epidermis.
AB  - The accidental or therapeutic exposure of human skin to ionizing radiation is
      known to cause the radiation syndrome with its various manifestations. The aim of
      the study was to investigate the potential radioprotective effects of the protein
      free hemodialysate Actovegin. After exposure to X-rays (single dose, 6 Gy), 70%
      of the cells died. In the presence of the hemodialysate, irradiation did not lead
      to cell death. Instead a slight increase in cell number was observed. A 5-fold
      increased cell number was found after 6 days when the cells were treated with the
      hemodialysate alone. To elucidate molecular mechanisms of the observed biological
      effects the correlation between the expression of the epidermal growth factor
      receptor (EGFR) and the demonstrated growth activation was investigated.
      Radiation alone resulted in a clear induction of EGFR, whereas the combination of
      irradiation and Actovegin treatment led to a strong downregulation after 2 days.
      Thus, the hemodialysate suppressed one of the radiation-induced effects. Further
      investigations have to elucidate the role of other proteins which are involved in
      the signal transduction cascade of tyrosine kinases (e.g. Ras, Raf, MAP kinases)
      leading to the transcription factor AP-1 in response to radiation under Actovegin
      treatment.

PMID- 8737918
TI  - Effects of inflammation on plasma extravasation and mast cell response in normal
      and denervated rat skin.
AB  - The effects of mild inflammation induced by topical chloroform treatment on
      plasma extravasation and mast cell response were studied in normal innervated and
      denervated rat skin. In the absence of inflammation, the reduction in plasma
      protein extravasation in response to noxious heat was 31.2% in denervated skin
      compared to the innervated skin. In the presence of inflammation, the reduction
      in this response was 52.5% in denervated skin compared to the innervated skin.
      During inflammation, mast cells became abundant, highly degranulated and migrated
      to the lower dermal tissue forming large aggregations. The ultrastructural
      observations showed a close anatomical relationship between mast cells and
      vesicle-containing nerve profiles. These results indicate that repeated topical
      chloroform treatment of the rat skin induces neurogenic vascular inflammation
      accompanied by an increase in mast cell response.

PMID- 8737919
TI  - Heterogeneity of human skin mast cells and human basophils. I. Pharmacological
      experiments with activators and inhibitors of protein kinase C.
AB  - Skin mast cells and basophilic leukocytes are known as key elements of acute and
      subacute IgE-mediated immune responses of the skin. The present paper
      investigated pharmacological aspects of signal transduction pathways of both cell
      types using activators and inhibitors of protein kinase C (PKC). The nonselective
      inhibitor K252a suppressed Fc epsilon RI-mediated histamine release from
      basophils and skin mast cells dose-dependently with IC50 values of 0.01 and 0.28
      mumol/l. However, preincubation of both cell populations with kinase inhibitors
      showing in vitro selectivity for PKC (Ro 31-7549, calphostin C, GF 109203X)
      revealed a distinct modulation of cell response: IgE-mediated mediator release
      was inhibited only in skin mast cells, whereas in experiments with basophils a
      concentration-dependent potentiation of exocytosis was observed. Further evidence
      for heterogenous biochemical signals following activation of both cell types
      derived from studies with the phorbol ester TPA. With respect to acute and late
      phase IgE-mediated skin reactions, we suggest that distinct signal transduction
      mechanisms at the level of PKC (isozymes) in basophils and skin mast cells might
      reflect their functional heterogeneity.

PMID- 8737920
TI  - Metabolism of benzocaine during percutaneous absorption in the hairless guinea
      pig: acetylbenzocaine formation and activity.
AB  - The effect of dose and enzymatic inhibition on the percutaneous absorption and
      metabolism of benzocaine was studied in vitro in the hairless guinea pig. At the
      dose level of 2 micrograms/cm2, benzocaine was rapidly absorbed and extensively
      metabolized (80%) by acetyltransferase. As the applied dose of benzocaine was
      increased to 40 and 200 micrograms/cm2, N-acetylation of benzocaine decreased to
      44 and 34%, respectively, suggesting saturation of the acetyltransferase system.
      Total 14C absorption after benzocaine application was not significantly different
      between control and enzyme-inhibited skin and therefore does not appear to be
      affected by the extent of benzocaine metabolism during percutaneous penetration.
      Skin provides a significant first-pass metabolic effect for therapeutic doses of
      percutaneously absorbed benzocaine, and the primary metabolite formed,
      acetylbenzocaine, is biologically active.

PMID- 8737921
TI  - Mouse inoculation studies reveal no transmissible agent in amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) resembles the spongiform encephalopathies in
      its dual pattern of inherited and sporadic cases, its uniform prevalence in
      different populations, its late onset (suggestive of a long incubation period)
      and its pathological picture of neuronal degeneration without inflammation. There
      is a well-established protocol for primary transmission of scrapie and related
      diseases to mice. Using this, we inoculated four longlived, inbred, mouse strains
      with cord material fresh-frozen within three hours of death, from a case of ALS
      or a control case. No motor neuron loss, gliosis or tract demyelination was found
      in the experimental group. Fifty per cent of each group were observed for more
      than 600 days. Two types of lesions were found in these animals at death:
      widespread foci of white matter vacuolation and bilateral thalamic mineral
      deposits. They were present in the control group at the same incidence and
      severity as in the experimental group and were thus considered to represent an
      age-related change. Attention is drawn to them because they have been claimed as
      significant when found in a transgenic model of spongiform encephalopathy. The
      results of our carefully-controlled experiment suggest that it is unlikely that
      ALS is caused by a scrapie-like agent capable of transmission to mice.

PMID- 8737922
TI  - The search for a transmissible agent in ALS.

PMID- 8737923
TI  - Cerebral amyloid beta protein deposits and other Alzheimer lesions in non
      demented elderly east Africans.
AB  - There is little knowledge of the existence of Alzheimer disease (AD) or Alzheimer
      type of dementia in indigenous populations of developing countries. In an effort
      to evaluate this, we assessed the deposition of amyloid beta (A beta) protein and
      other lesions associated with AD in brains of elderly East Africans. Brain
      tissues were examined from 32 subjects, aged 45 to 83 years with no apparent
      neurological disease, who came to autopsy at two medical Institutions in Nairobi
      and Dar es Salaam. An age-matched sample from subjects who had died from similar
      causes in Cleveland was assessed in parallel. Of the 20 samples from Nairobi, 3
      (15%) brains exhibited neocortical A beta deposits that varied from numerous
      diffuse to highly localized compact or neuritic plaques, many of which were also
      thioflavin S positive. Two of the cases had profound A beta deposition in the
      prefrontal and temporal cortices and one of these also exhibited moderate to
      severe cerebral amyloid angiopathy. Similarly, 2 of the 12 samples from Dar es
      Salaam exhibited diffuse and compact A beta deposits that were also predominantly
      reactive for the longer A beta 42 species compared to A beta 40. We also noted
      that A beta plaques were variably immunoreactive for amyloid associated proteins,
      apolipoprotein E, serum amyloid P and complement C3. Tau protein reactive
      neurofibrillary tangles (NFT) were also evident in the hippocampus of 4 subjects.
      By comparison, 4 (20%) of the 20 samples from randomly selected autopsies
      performed in Cleveland showed A beta deposits within diffuse and compact
      parenchymal plaques and the vasculature. These observations suggest A beta
      deposition and some NFT in brains of non-demented East Africans are qualitatively
      and quantitatively similar to that in age-matched elderly controls from
      Cleveland. While our small scale study does not document similar prevalence rates
      of preclinical AD, it suggests that elderly East Africans are unlikely to escape
      AD as it is known in developed countries.

PMID- 8737924
TI  - Pathological aging in Africans: a benign form of cerebral amyloidosis vs. pre
      clinical Alzheimer's disease?

PMID- 8737925
TI  - Introduction to the Amyloid Symposium.

PMID- 8737926
TI  - Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D): I--A review
      of clinical, radiologic and genetic aspects.
AB  - Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) is an
      autosomal dominant disease caused by deposition of beta-amyloid in the
      leptomeningeal arteries and cortical arterioles, in addition to preamyloid
      deposits and amyloid plaques in the brain parenchyma. The disease is due to a
      point mutation at codon 693 of the amyloid precursor protein (beta PP) gene at
      chromosome 21. Since this point mutation is diagnostic for HCHWA-D,
      presymptomatic testing is feasible and offered, together with genetic counselling
      and psychological support, to subjects at risk. HCHWA-D is clinically
      characterized by recurrent strokes, in addition to dementia, which can occur
      after the first stroke but also preceding it. Radiological studies revealed focal
      lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse
      white matter damage. Diffuse white matter hyperintensities on MRI are an early
      symptom of HCHWA-D since they have been found on MRI scans of subjects who had
      not suffered a stroke. The presence of the diagnostic point mutation makes HCHWA
      D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The
      characteristic pathological abnormalities and its implications for Alzheimer's
      disease will be discussed in Part II of this article.

PMID- 8737927
TI  - Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D): II--A
      review of histopathological aspects.
AB  - Cerebral amyloid-beta (A beta) angiopathy is the histopathological hallmark of
      hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D). A beta
      deposits are found mainly in the cerebral and cerebellar meningocortical blood
      vessels and as plaques throughout the cerebrocortical gray matter. A beta
      deposition in arteries and arterioles starts at the junction of media and
      adventitia and proceeds to involve the media causing degeneration of the vascular
      smooth muscle cells. Cerebrocortical arterioles often show one or two layers of
      radial A beta around a layer of homogenous A beta that replaces the media.
      Degenerating neurites, reactive astrocytes and microglial cells may surround
      cerebrocortical angiopathic arterioles and capillaries, probably in reaction to
      invasion of the perivascular neuropil by A beta fibrils. Furthermore, clusters of
      coarse extracellular matrix deposits may be found near A beta-laden
      cerebrocortical arterioles. The amyloid-associated proteins, cystatin C, and beta
      PP colocalize diffusely with Dutch vascular A beta, whereas HLA-DR
      immunoreactivity is found only in the periphery of the diseased vessel wall. The
      latter phenomenon may be related to the presence of perivascular cells.
      Angiopathic blood vessels frequently show structural changes. The relation of the
      described pathology to the development of hemorrhage, infarction and
      leukoencephalopathy needs further elucidation.

PMID- 8737928
TI  - The molecular pathology of hereditary cystatin C amyloid angiopathy causing brain
      hemorrhage.
AB  - Knowledge about molecular pathology of hereditary cystatin C amyloid angiopathy
      (HCCAA), also called hereditary cerebral hemorrhage with amyloidosis, Icelandic
      type, has increased greatly in the last decade. The disorder has an autosomal
      dominant mode of inheritance and causes fatal brain hemorrhage in normotensive
      young adults. It is due to a mutation in the gene encoding the cysteine
      proteinase inhibitor, cystatin C.A single nucleotide is substituted, A for T, in
      the codon 68, resulting in glutamine replacing leucine in the protein sequence.
      This variant protein has an increased tendency to aggregate and forms heavy
      depositions of amyloid in the walls of the small arteries and arterioles of the
      brain. The amyloid deposition leads to arterial damage with single or multiple
      strokes. In the following review the clinical features, family studies,
      pathology, biochemistry and molecular genetics of HCCAA are addressed.

PMID- 8737930
TI  - Brain amyloid--a physicochemical perspective.
AB  - The ability to form stable cross-beta fibrils is an intrinsic physicochemical
      characteristic of the human beta-amyloid peptide (A beta), which forms the brain
      amyloid of Alzheimer's disease (AD). The high amyloidogenicity and low solubility
      of this hydrophobic approximately 40-mer have been barriers to its study in the
      past, but the availability of synthetic peptide and new physical methods has
      enabled many novel approaches in recent years. Model systems for A beta
      aggregation (relevant to initial nidus formation) and A beta deposition (relevant
      to plaque growth and maturation) in vitro have allowed structure/activity
      relationships and kinetics to be explored quantitatively, and established that
      these processes are biochemically distinct. Different forms of the peptide, with
      different physiochemical characteristics, are found in vascular and parenchymal
      amyloid. Various spectroscopic methods have been used to explore the three
      dimensional conformation of A beta both in solution and in solid phase, and
      demonstrated that the peptide adopts a different configuration in each state. A
      significant conformational transition is essential to the transformation of A
      beta from solution to fibril. These observations suggest new therapeutic targets
      for the treatment of AD.

PMID- 8737929
TI  - Prion protein amyloidosis.
AB  - The prion protein (PrP) plays an essential role in the pathogenesis of a group of
      sporadic, genetically determined and infectious fatal degenerative diseases,
      referred to as "prion diseases", affecting the central nervous system of humans
      and other mammals. The cellular PrP is encoded by a single copy gene, highly
      conserved across mammalian species. In prion diseases, PrP undergoes
      conformational changes involving a shift from alpha-helix to beta-sheet
      structure. This conversion is important for PrP amyloidogenesis, which occurs to
      the highest degree in the genetically determined Gerstmann-Straussler-Scheinker
      disease (GSS) and prion protein cerebral amyloid angiopathy (PrP-CAA), while it
      is less frequently seen in other prion diseases. GSS and PrP-CAA are associated
      with point mutations of the prion protein gene (PRNP); these conditions show a
      broad spectrum of clinical presentation, the main signs being ataxia, spastic
      paraparesis, extrapyramidal signs and dementia. In GSS, parenchymal amyloid may
      be associated with spongiform changes or neurofibrillary lesions; in PrP-CAA,
      vascular amyloid is associated with neurofibrillary lesions. A major component of
      the amyloid fibrils in the two diseases is a 7 kDa peptide, spanning residues 81
      150 of PrP.

PMID- 8737931
TI  - Peripheral nerve amyloidosis.
AB  - Peripheral nerve amyloidosis is the cardinal feature of familial amyloid
      polyneuropathy (FAP) but can also be seen in primary light chain (AL) amyloidosis
      and dialysis (beta 2-microglobulin) related amyloidosis. The generalized
      neuropathy seen in all forms of peripheral nerve amyloidosis is similar,
      characterized by a severe progressive mixed neuropathy with autonomic
      dysfunction. Pathologically, amyloid is found in the peripheral nervous system as
      amorphous, eosinophilic, extracellular deposits. FAP is most commonly associated
      with variant plasma transthyretin (TTR), although it has also been described in
      association with mutant apolipoprotein A-1 and gelsolin. There are now at least
      36 point mutations in the TTR gene associated with FAP and these continue to be
      described. Recent studies on the possible role individual point mutations in the
      TTR gene may play in amyloidosis have helped give us an insight into the
      mechanisms behind peripheral nerve amyloidosis. This article reviews the clinical
      and pathological features of the peripheral nerve amyloidosis and discusses
      theories of amyloidogenesis based on studies of FAP.

PMID- 8737932
TI  - Brain parenchymal and microvascular amyloid in Alzheimer's disease.
AB  - Brains of patients with Alzheimer disease/senile dementia of Alzheimer type
      (AD/SDAT) develop a progressive accumulation of amyloid, which deposits primarily
      in the form of characteristic parenchymal 'plaques' (senile or neuritic
      plaques/SP's) and as mural deposits in the walls of capillaries and arterioles
      (cerebral amyloid angiopathy /CAA). A major component of this amyloid is a small
      and unique peptide composed of 39-43 amino acids, beta/A4, which is cleaved from
      a much larger precursor protein (APP) that has several isoforms. Brain amyloid
      can be detected in autopsy or biopsy brain tissue by classical,
      immunohistochemical and ultrastructural (including immuno-electron microscopic)
      methods of varying sensitivity and specificity. Beta/A4 amyloid deposition is
      remarkably variable (e.g. predominantly parenchymal or vascular, or a mixture of
      parenchymal and vascular) among patients with AD/SDAT. Despite its abundance in
      the brains of AD/SDAT patients, the precise role of beta/A4 in the pathogenesis
      of the neurological deficit, neocortical atrophy and progressive synapse loss
      associated with AD/SDAT has yet to be determined. However, mutations in the gene
      that encodes APP are clearly associated with familial AD syndromes in which there
      is significant brain amyloid deposition. CAA, in addition to its association with
      AD/SDAT, can result in hemorrhagic and (possibly) ischemic forms of stroke. Work
      with recently developed transgenic mice which express large amounts of beta/A4 in
      the central nervous system is likely to elucidate mechanisms by which the protein
      is selectively or deposited in the brain in a parenchymal or microvascular form,
      and how it contributes to the pathogenesis of neurodegeneration.

PMID- 8737933
TI  - Inactivation of the causal agents of Creutzfeldt-Jakob disease and other human
      prion diseases.

PMID- 8737934
TI  - Somatosensory cortical and dermatome evoked potentials: a study conducted on 60
      normal subjects. Results and their correlation relative to height and age.
AB  - The somatosensory cerebral evoked potentials of the median and tibial nerves (N
      20, P 38), as well as dermatome evoked potentials by stimulation of specific
      dermatomes corresponding to the roots C5, C6, C7, C8-T1, L3, L4, L5 and S1, were
      recorded on the scalps of 73 normal subjects. The height and age of each subject
      were noted. Of the 73 subjects studied, 60 were withheld for the protocol. The
      technique and constants used for recording are explained, as well as the results
      obtained. A statistical analysis was undertaken, using parametric and non
      parametric methods. The latter enabled us to determine the averages, standard
      deviation, median and percentile for each of the latencies. A study by
      correlation allows for a comparison between the left and the right sides, and
      between the various dermatomes. For median and tibial nerves and for each
      dermatome latency values are correlated to subjects' height and age. Thus, it is
      possible to show the absence of correlation between the median nerve, the
      dermatomes of upper limbs with age and height, whereas there exists a perfect
      correlation with age and height for the tibial nerves and the dermatomes of lower
      limbs. All normal results adjusted to height and age are given.

PMID- 8737935
TI  - Clinically and electrodiagnostically pure sensory demyelinating polyneuropathy.
AB  - A 35-year-old woman presented with a 4 year history of stepwise sensory loss
      which progressed in an asymmetrical fashion (mononeuropathy multiplex) and
      developed into a relatively symmetric polyneuropathy which was purely sensory by
      clinical and electrodiagnostic criteria. Sural nerve biopsy revealed
      demyelination with axonal sparing. Extensive laboratory evaluation failed to
      reveal a definite cause. This case is unique among well-documented cases of
      chronic inflammatory demyelinating polyneuropathy (CIDP) in that it is purely
      sensory by both clinical and electrodiagnostic criteria, and may represent a
      distinct entity rather than an extension of the spectrum of CIDP.

PMID- 8737936
TI  - Schwartz-Jampel syndrome: clinical, electromyographic and genetic studies.
AB  - Two sisters aged 9 and 7 from consanguineous parents are described. Both of them
      develop myotonia, muscular weakness as early as the first year after birth. At
      the age 3-4 a disturbed gait appeared due to knee joint contractures and limited
      joint movements. The children display facial dysmorphism (a small forehead, a
      flat base of the nose, a receding chin, an irregular order of the teeth, low-set
      ears, a high-arched palate, low hair-line), kyphoscoliosis, pigeon breast, severe
      contractures of the knee and elbow joint and foot deformities. The elder sister
      cannot walk. Hirsutism of all four limbs is found as well as sparse subcutaneous
      tissue. Muscles are stiff and firm. Tendon reflexes of the lower limbs are
      absent. Muscle enzymes show slightly increased values. The EMG needle examination
      in both sisters was abnormal. Spontaneous, continuous, high-frequency, low
      voltage electrical discharges were observed in all distal and proximal muscles of
      the hands and legs. Some of them have a typical myotonic pattern. The MCV and the
      SCV was within the normal range. Both parents of our patients, their sister aged
      4, as well as their grandparents showed no clinical and EMG abnormalities. All
      these data allow authors to affirm the diagnosis chondrodystrophic myotonia.,
      described for the first time in Bulgaria.

PMID- 8737937
TI  - Relaxation electromechanical delay of the quadriceps during selected movement
      velocities.
AB  - The purpose of this study was to quantify the time between the cessation of EMG
      activity and cessation of torque production, or relaxation electromechanical
      delay, (R-EMD) of the quadriceps at three angular movement velocities. A Biodex
      dynamometer passively moved the right knee of 25 males through a given range at
      three velocities (10, 60 and 120 degrees per second). Subjects were instructed to
      actively extend their knees to a visual target, then to immediately relax. Biodex
      torque and position data, as well as surface EMG from the right Vastus Medialis
      (VM), Rectus Femoris (RF) and Vastus Lateralis (VL) were sampled simultaneously.
      EMG cessation was determined when activity fell below a threshold based on the
      muscle's resting EMG. Torque cessation was determined when the slope of the
      relaxation curve decreased to 10% of the initial value. R-EMD time for each
      quadriceps head at each velocity was determined by calculating the difference
      between these two times. To examine reliability, subjects were retested four days
      later. Approximately two thirds of the subjects were unable to consistently
      perform the motor task of abrupt relaxation at some or all of the tested
      velocities. This variability was ascribed to motor control issues. Average R-EMD
      times for all subjects, muscle segments and velocities ranged from 249 +/- 68 ms
      to 276 +/- 51 ms during the first test session, and 239 +/- 46 ms to 300 +/- 59
      ms during the second session. These data are important in identification of
      physiologically meaningful cessation of muscle contraction, and may be beneficial
      in research studies focusing on the areas of motor control and motor learning,
      computerized movement analysis, and prediction models for the determination of
      muscular force from the EMG signal.

PMID- 8737938
TI  - Median-radial sensory latencies comparison as a new test in carpal tunnel
      syndrome.
AB  - Median and radial distal sensory latencies (DSL) were compared in 50 patients
      with carpal tunnel syndrome (CTS) and 50 healthy subjects by stimulating each
      nerve separately and recording sensory nerve action potential (SNAP) from
      standard anatomical locations for stimulation and recording sites. The range of
      difference between median DSL and radial DSL was 0.18 -1.18 msec in control group
      and 1.12-4.46 msec in CTS patients with a mean of 0.69 msec and 1.99 msec
      respectively (P < or = 0.0001). We found the value of 1 msec as a good cut-off
      point for diagnosis of CTS. The test described here seems to be an effective and
      simple criteria for increasing the sensitivity of nerve conduction studies in
      CTS.

PMID- 8737939
TI  - Distal, "Tinel-like" percussion paresthesiae, with proximal nerve lesions.
AB  - Can proximal nerve lesions cause a distal "Tinel-like" sign? We present the case
      studies of two patients with documented cervical root lesions who exhibited
      percussion paresthesiae distally in the absence of any clinical or nerve
      conduction evidence of distal pathology. The possible mechanisms underlying such
      manifestation, which has been previously reported in the literature, are
      explored, and a case is made for the phenomenon being related to the "distortion"
      of a normal sensory signal when it encounters an area of spatial inhomogeneity
      proximally along the nerve.

PMID- 8737940
TI  - Quantitative EMG in cervical dystonia.
AB  - Within the latest years botulinum toxin A (BT) applied locally in affected
      muscles has gained a superior position in the treatment of cervical dystonia. EMG
      is often used as a guidance for the injections, which has caused a need for
      better knowledge about the electromyographic changes in the muscles involved. In
      the present study we used the turns-amplitude analysis for the quantitative
      evaluation of the EMG of the sternocleidomastoid muscles and posterior neck
      muscles in 44 patients with cervical dystonia, not previously treated with BT.
      Twelve healthy subjects were examined for comparison. At rest 13 patients showed
      abnormal activity (defined as > 100 turns/s) in the sternocleidomastoid muscle
      contralateral to the involuntary head rotation (CS) and the ipsi- and
      contralateral posterior neck muscles (IPN and CPN): 12 patients had abnormal
      activity in CS and IPN, and seven patients had abnormal activity in all muscles,
      including the ipsilateral sternocleidomastoid muscle (IS). Other combinations
      were seen less often. The distribution of muscles with abnormal activity was not
      always obvious from the clinical examination. CPN and IS, i.e., apparently
      unaffected muscles, showed reduced EMG activity during attempted maximal
      voluntary contraction, indicating difficulties in activating all motor units.

PMID- 8737941
TI  - Application EMGs spectral analysis method for the objective diagnosis of
      different clinical forms of Parkinson's disease.
AB  - The authors work out a computer analysis method to investigate electrical
      activity of muscles (EMG). With four muscles (extensor carpi radialis longus and
      tibialis anterior of both right and left sides) integrated EMGs are introduced
      into the computer. EMG are detected and filtered the pass band from 0 to 15 Hz
      range, thus forming the envelope of EMG signals (EEMG). Spectral Analyses of 20
      one-minute realizations of EEMG signals are conducted for each muscle. Diagnostic
      signs were obtained on the basis of a statistical treatment of the spectral
      parameters. Subsequent analysis of data obtained for 130 patients allowed to
      single out thereof the most informative signs. This signs were applied for
      studying 40 patients diagnosed with Parkinson's disease of different etiologies,
      clinical forms and stages. In a researched group, in 33 out 40 cases, clinical
      diagnosis coincided with computer one. In six cases, doctors corrected the
      diagnosis of the illness with diagnostic indicators. In one case, computer and
      clinical diagnosis did not coincide.

PMID- 8737942
TI  - Generation of DNA probes for detection of microorganisms by polymerase chain
      reaction fingerprinting.
AB  - Identification of medically relevant microorganisms is important for diagnosis,
      treatment and prevention of infectious diseases. This has initiated the
      development of a large number of identification and typing techniques based on
      phenotypic and genetic characteristics. In general, these last mentioned nucleic
      acid-mediated techniques provide more detailed and consistent information on
      strain-specific characteristics. However, the development of clinically useful
      microbial DNA/RNA probes requires nucleotide sequence information and a set of
      well defined reference organisms for test validation in comparison with the
      current gold standard. This is a requirement for the development of accurate
      nucleic acid hybridisation and/or amplification tests. Recently, it has been
      demonstrated that polymerase chain reaction (PCR)-mediated genetic typing of
      microorganisms can lead to the immediate isolation of species-specific DNA probes
      by comparison of DNA fingerprints. This combines the sensitivity of PCR with the
      specificity of DNA probing without the need to generate nucleic acid sequence
      information prior to probe development. The implications of this procedure for
      clinical microbiology and epidemiological surveillance will be discussed. It is
      shown that specific probes can be developed for various taxonomic levels and that
      detection and identification can be combined into a single, fast procedure. The
      versatility and widely applicable principles of this procedure will be
      highlighted and exemplified by some newly developed tests and a review of the
      current literature.

PMID- 8737944
TI  - Discrimination of S. aureus strains by PCR for r-RNA gene spacer size
      polymorphism and comparison to SmaI macrorestriction patterns.
AB  - The size polymorphism of the internal spacer between the 16 S and the 23 S r-RNA
      genes was studied in S. aureus with the aid of PCR. The patterns of corresponding
      PCR products were compared with SmaI-generated macrorestriction patterns for
      definite propagating strains of S. aureus typing phages, for strains with phage
      pattern 29, phage-group II patterns, phage pattern 94, 96, phage pattern 95 and
      epidemic methicillin-resistant strains (MRSA). The spacer length polymorphism did
      not prove to be as discriminative as genomic DNA fragment patterns. However, as
      shown for S. aureus with phage patterns 29; group II; 94, 96; 95 and also for 4
      out of 6 epidemic MRSA, unique patterns of r-RNA gene spacers probably indicate a
      relatedness among strains which is also suggested by SmaI macrorestriction
      patterns.

PMID- 8737943
TI  - Problems and priorities for controlling opportunistic pathogens with new
      antimicrobial strategies; an overview of current literature.
AB  - An International Study Group on New Antimicrobial Strategies (ISGNAS) has been
      formed in response to the recognition that development of microbial resistance to
      antibiotics is becoming a serious, world-wide problem. The group met in 1993 for
      the first time to discuss the feasibility of developing rational alternatives to
      the use of antibiotics and prepared, as a result, a comprehensive overview of
      normal (physiological) mechanisms involved in the control of potentially
      pathogenic (oppotunistic) microorganisms. One objective of ISGNAS is to
      understand the conditions which allow opportunistic microbes present among the
      symbionts to cause an infection. There is a need for more coherent information
      concerning the habitat, growth requirements and host and pathogen properties
      which allow opportunistic pathogens to cause life-threatening infections. In
      particular, information is urgently being sought to understand the complexity of
      the interactions between the vast number of microbial species, and the
      interactions between the microbes and their host. Another goal is to inspire and
      enable basic and clinical research that will lead to the development of new
      therapies for regulating colonization, translocation and infection by
      opportunistic micro-organisms in patients during periods of decreased resistance.
      With a sufficient amount of knowledge of how healthy individuals keep
      opportunistic micro-organisms under control, it may become feasible for
      physicians to maintain host resistance and inter-microbial factors involved in
      the containment of opportunistic microbes. Therapies aimed at boostering natural
      resistance mechanisms will be of critical importance to individuals whose
      resistance has been compromised as a result of another clinical condition.

PMID- 8737945
TI  - Enzyme-linked immunosorbent assay, complement fixation test and
      immunoelectroprecipitation test in the diagnosis of Mycoplasma pneumoniae
      infections--comparative analysis.
AB  - Agreement of the results of determining antibodies against M. pneumoniae was
      evaluated by ELISA, complement fixation test (CFT) and immunoelectroprecipitation
      test (IEPT) in serum samples from 685 persons including 571 patients with
      respiratory tract infections and 114 clinically healthy subjects. Assuming the CF
      test to be the reference test, a very high correlation exceeding 0.95 was found,
      on the basis of the calculated correlation coefficient, between the results of
      the CF and IEP tests and the CFT and ELISA for all immunoglobulin classes. The
      highest sensitivity (92.3%) was displayed by the ELISA in relation to the CF test
      when determining mycoplasmal antibodies of Ig M and Ig A+G+M classes and a
      slightly lower sensitivity by the IEPT and ELISA when determining Ig G (83% and
      82.1%, respectively). The lowest sensitivity was displayed by the ELISA when
      determining mycoplasmal antibodies of the Ig A class (53.4%). The specificity of
      both tests was high and exceeded 92%. The highest agreement of CFT and ELISA was
      obtained when detecting mycoplasmal antibodies in a diagnostically significant
      titre in the M and A+G+M immunoglobulin classes (> 92%) while the lowest
      agreement, although statistically significant, was obtained when detecting Ig A
      antibodies (74.7%).

PMID- 8737946
TI  - Invasive ability of C. jejuni/coli isolates from children with diarrhea and the
      effect of iron-regulated proteins.
AB  - The invasive ability of C. jejuni/coli strains isolated from children with
      diarrhea was studied using an in vitro HEp-2 cell invasion assay. The ratio
      between the number of intracellular bacteria and the number of bacteria in the
      inoculum was determined (invasion index). It was found that under anaerobic
      conditions, there was a significant decrease in the invasion index as compared to
      standard conditions (5% CO2). Of 11 strains tested, seven were determined as
      invasive on the basis of invasion indexes within the range of 0.0002-0.01. In a
      previous study [D. Schwartz et al., Zbl. Bakt. 280, 338-347 (1994)], it was
      found, that most of the C. jejuni/coli isolates tested produced an outer membrane
      protein when grown under conditions of iron depletion (IRP). The IRP were
      detected in eight of the nine strains tested in the present study (five invasive
      and three non-invasive strains). In one non-invasive strain, IRP was not
      detected. When kept under conditions of iron depletion, one of the invasive
      strains exhibited a significant increase in invasive capacity. The results
      suggest that iron depletion seems to stimulate the invasion capacity of C.
      jejuni/coli in vitro.

PMID- 8737947
TI  - Serum level determination of fluconazole by high-performance liquid
      chromatography and bioassay.
AB  - An HPLC method using a reverse phase system, an isocratic mobile phase and 1
      phenyl-1,2 ethanediol as internal standard and a well diffusion bioassay using a
      strain of Candida pseudotropicalis were compared for the measurement of
      fluconazole in serum. Both methods permit determination of fluconazole in the
      range from 1 mg/L to 30 mg/L. The correlation between both methods was found to
      be r = 0.89. Both methods are useful for monitoring the serum level of
      fluconazole in clinical routine work.

PMID- 8737948
TI  - In-vitro activity of RP 59500, a new semisynthetic injectable pristinamycin
      against staphylococci.
AB  - We compared the in vitro activity of RP 59500, a new streptogramin, with that of
      vancomycin and ciprofloxacin against 130 strains of S. aureus and 117 strains of
      coagulase-negative staphylococci, using the agar dilution method. The
      antistaphylococcal activity of RP 59500 was similar to that of vancomycin. All
      staphylococcal strains were inhibited by < or = 2 micrograms/mL, including 61
      methicillin-resistant S. aureus, 28 methicillin-resistant S. epidermidis and 23
      methicillin-resistant S. haemolyticus strains. In contrast to ciprofloxacin, the
      in vitro activity of RP 59500 as well as of vancomycin remained almost unchanged,
      irrespective of the resistance phenotype for methicillin.

PMID- 8737949
TI  - Aluminosilicates enhance the infectivity of cytomegalovirus in urine using
      centrifugation-enhanced antigen detection technology.
AB  - Due to the inherent lability of CMV, necessary laboratory identification of this
      infectious agent is often compromised by a delay in specimen transport. Previous
      studies have addressed the phenomenon of infectivity enhancement/reduction in the
      rate of infectivity loss by the incorporation into various viral assay systems of
      trace concentrations of the adsorbents montmorillonite (bentonite [M]) or
      kaolinite (kaolin [K]). We extended these studies to the clinical setting to
      identify whether such aluminosilicates would effect an enhanced level of CMV
      infectivity. The shell vial assay-indirect immunofluorescent assay (SVA-IFA) was
      utilized in comparative testing throughout this study. The addition of trace
      concentrations of M or K to the SVA-IFA was found to enhance the infectivity of
      CMV in urine by 115 and 126%, respectively. The total CMV detection rate by SVA
      IFA was 29% (30/105). Three of the 30 (10%) CMV positive specimens were detected
      only in shell vials which had been supplemented with K or M. Two specimens were
      isolation positive alone. The addition of K or M to shell vials immediately prior
      to the start of the SVA-IFA has the potential of (a), enhancing assay readability
      by increasing the number of fluorescent focus units per vial monolayer and (b),
      of detecting positive urine specimens with low viral titers which might otherwise
      not be identified using the conventional SVA-IFA procedure.

PMID- 8737950
TI  - Brown-red pigment formation by the mycelial phase of a clinical isolate of
      Histoplasma capsulatum on Staib agar. A preliminary report.
AB  - In an HIV-positive patient, the suspected diagnosis of histoplasmosis capsulatum
      (being the first opportunistic infection indicating AIDS) on the basis of
      histopathological findings in biopsy material could be proved by culture on Staib
      agar (syn. Guizotia abyssinica creatinine agar, bird seed agar, etc.). On Staib
      agar, after 4 weeks at 26 degrees C, there was a cockade-like colony growth,
      consisting of a white centre, followed by a brown-red pigmented zone surrounded
      by a border of submerged mycelial growth of tan to brownish colour.
      Morphologically, there was a moderate formation of tuberculate macroconidia and a
      heavy formation of microconidia. On neutral Sabouraud's dextrose agar, there was
      a colony formation without pigment (albino type) free of tuberculate macroconidia
      and microconidia. Proposals for further investigation of these preliminary
      observations are made.

PMID- 8737951
TI  - Recovery efficiency of Cryptosporidium from water with a crossflow system and
      continuous flow centrifugation: a comparison study.
AB  - A crossflow system and continuous flow centrifugation were tested with regard to
      the recovery rate of Cryptosporidium oocysts from water. Equal volumes of tap
      water were contaminated with specific numbers of oocysts. With the crossflow
      system, an average recovery of 9.8% was obtained when using a concentration of 2
      x 10(2) oocysts/L. Recovery rates achieved with the continuous flow centrifuge
      were more satisfactory: Starting with a concentration of 80 oocysts/L, we
      obtained an average recovery of 12.9%. The technique of continuous flow
      centrifugation was found to be more efficient for collection of Cryptosporidium
      oocysts from water than the crossflow system.

PMID- 8737952
TI  - Frequency, clonal heterogeneity and antibiotic resistance of methicillin
      resistant Staphylococcus aureus (MRSA) isolated in 1992-1994.
AB  - Since 1992, the proportion of methicillin-resistant Staphylococcus aureus (MRSA)
      isolated from patients of the University Hospital of Frankfurt/Main and six
      community hospitals increased to a level of 11% and has remained constant during
      the following two years. MRSA and methicillin-sensitive Staphylococcus aureus
      (MSSA) were distributed equally among almost all specimens except blood. There
      was evidence of a diminished potency of MRSA to cause bacteremia. All MRSA
      strains were susceptible to glycopeptides and mupirocin. Resistance rates to
      other non-beta-lactam antibiotics were low for fusidic acid (7.1%), fosfocin
      (8.3%), amikacin (11.4%) and cotrimoxazole (18.3%) and high for gentamicin
      (90.7%), ofloxacin (94.3%) and erythromycin (95.5%). Among 378 MRSA strains
      originating from 180 individuals, macrorestriction analysis of chromosomal DNA
      revealed 39 different genotypes. These could be divided into 14 epidemic strains
      isolated from 155 patients and 25 sporadic strains isolated from single patients.
      As most of the sporadic strains emerged in close local proximity to epidemic
      strains, we suppose a horizontal genetic transfer from MRSA to MSSA leading to
      the appearance of novel MRSA genotypes. Upon repeated isolation of MRSA strains
      from the same individuals, resistance rates and genotypes remained stable.
      Resistance patterns of the non-beta-lactams correlated poorly with
      macrorestriction analysis, whereas several MRSA genotypes could be distinguished
      by particular MICs of methicillin.

PMID- 8737953
TI  - Recent status of the antisense oligonucleotide approaches in oncology.
AB  - Antisense oligonucleotides designed to complement a region of a particular
      messenger RNA may inhibit gene expression potentially through sequence-specific
      hybridization. Their inhibiting effect has been shown in a variety of in vitro
      and in vivo models in oncology, whereas much rarer clinical trials have been
      carried out. Rigorous demonstration of in vitro and in vivo specific effects upon
      their targets is mandatory before their use as drugs in cancer therapy.

PMID- 8737954
TI  - Two faces of cholecystokinin: anxiety and schizophrenia.
AB  - It has been suggested that cholecystokinin (CCK), a gut-brain peptide found in
      high concentrations in the mammalian brain, might be implicated in the
      neurobiology of anxiety and panic disorder. The administration of CCK
      tetrapeptide induced panic attacks analogous to spontaneous ones in patients
      suffering from panic disorder and to a lesser degree in healthy volunteers. In
      animal models of anxiety, the pretreatment with CCK agonists and antagonists
      produced, respectively, anxiogenic- and anxiolytic-like action on the exploratory
      paradigms. On the other hand, CCK could also play a role in the pathophysiology
      of schizophrenia. The administration of CCK agonists (caerulein, CCK-8s) to
      rodents results in behavioural effects analogous to those of antipsychotic drugs.
      However, CCK agonists lack any activity in rodent behavioural models to reveal
      antipsychotic drugs. A significant reduction of CCK concentration and CCK
      receptors has been shown in cortical and limbic structures of patients suffering
      from schizophrenia. Nevertheless, administration of CCK agonists to these
      patients does not effect their symptoms. Two major conclusions should be drawn:
      first, CCK is involved in the neurobiology of anxiety; second, changes in the CCK
      system in schizophrenia could be linked to a cortical neurodegeneration related
      to this disease.

PMID- 8737955
TI  - Systemic, pulmonary, brachial, renal and hepato-splanchnic hemodynamic effects of
      spirapril in severe congestive heart failure.
AB  - The effects of a single oral dose (6 mg) of the angiotensin-I converting enzyme
      inhibitor, spirapril, on systemic, pulmonary and regional (brachial, renal,
      hepato-splanchnic) hemodynamics as well as on biological parameters investigating
      the renin-angiotensin-aldosterone and sympathetic nervous systems were studied
      over a 24-hour period in eight patients with severe congestive heart failure
      (CHF). As compared to pretreatment values, spirapril significantly decreased mean
      arterial (-19%, peak effect), right atrial (-42%), mean pulmonary arterial (-38%)
      and pulmonary capillary wedge (-46%) pressures. Spirapril significantly decreased
      heart rate (-14%) and increased stroke volume index (+43%) thus resulting in a
      slight increase in cardiac index. All these effects were maximal between 2.5 and
      4 h. Brachial artery diameter (+12%) and brachial (+41%) and renal (+36%) blood
      flows increased significantly whereas brachial (-41%) and renal (-36%) vascular
      resistances decreased significantly. All these effects were usually maximal
      between 1 and 2.5 h. Hepato-splanchnic hemodynamics were not drug-affected.
      Spirapril significantly inhibited plasma converting enzyme activity (-96% at 4
      h), increased plasma renin activity (+505% at 4 h), and decreased plasma
      aldosterone (-46% at 24 h), norepinephrine (-31% at 24 h) and atrial natriuretic
      factor (-33% at 7 h). Thus, in severe CHF, acute administration of spirapril, 6
      mg orally, exerts both arterial and venous vasodilating properties and improves
      both the systemic and regional hemodynamics and the biological status of the
      patients.

PMID- 8737956
TI  - Effects of nitric oxide and sodium nitroprusside on the intrinsic elastic
      properties of pressurized rat coronary artery.
AB  - The study was designed to assess the influence of either nitric oxide (NO) or
      sodium nitroprusside and the absence of endothelium on the intrinsic elastic
      properties of coronary arteries from WKY rats. For this purpose, segments of the
      right interventricular coronary were mounted in an arteriograph where wall
      thickness and internal diameter were continuously monitored while intraluminal
      pressure was controlled in the absence of flow. To study the passive properties,
      pressure-diameter relationships were determined by measuring the corresponding
      internal diameter for each stepwise increase in intraluminal pressure. Thus, wall
      stress, strain and incremental elastic modulus (Einc) were assessed in the
      following experimental conditions: control, incubation with nitro-L-arginine
      methyl ester (L-NAME, 100 microM) or L-NAME + L-arginine (L-arg, 100 microM),
      incubation with sodium nitroprusside (SNP, 100 microM), endothelium removal
      (CHAPS). The Einc-stress relationship was not significantly different in the
      different experimental conditions, but values of Einc plotted as function of
      strain were significantly decreased after L-NAME incubation and partly reversed
      after L-arg addition. The same effect was observed after endothelium destruction
      but to a lesser extent. After SNP incubation, values of Einc were significantly
      decreased for small values of strain and increased for high values of this
      parameter. These results show that NO synthase inhibition induced, for a given
      strain, a decrease of elastic modulus in coronary arteries. It can be speculated
      that functional antagonism exerted by NO against spontaneous contractile tone was
      reduced. Thus, the smooth muscle cells were in a greater state of activation and
      probably more strongly involved in the intrinsic elastic properties of this
      preparation. However, an unexplained effect of NO on wall stiffness cannot be
      excluded. Conversely, SNP increased the initial diameter and induced an initial
      decrease in stiffness followed by a subsequent increase. After endothelium
      destruction, stiffness was significantly decreased compared to control
      conditions. It can be concluded that NO modulates the intrinsic elastic
      properties of the coronary arteries through smooth muscle cell relaxation.
      Furthermore, results with SNP support the hypothesis that the lower the state of
      activation of the smooth muscle cells, the higher the elastic modulus of the
      arterial wall in this coronary artery preparation.

PMID- 8737957
TI  - Effect on gastric secretion, gastrin and histamine release during and after long
      term treatment by pirenzepine in dogs.
AB  - We assessed the effects of pirenzepine (2 mg/kg per os) on gastric secretion and
      gastrin and histamine release in response to food and histamine dihydrochloride
      infusion in four dogs during 24 weeks of treatment and for 15 weeks after the end
      of treatment. The results were compared to those obtained in the same animals in
      control experiments, before treatment, and in four untreated dogs. Pirenzepine
      absorption was checked by measuring plasma concentrations. Pirenzepine led to a
      significant reduction in acid and pepsin secretion in response to histamine. In
      response to food, the reduction in secretion was concomitant with a reduction in
      gastrin and histamine release. Baseline concentrations of gastrin were reduced,
      while those of histamine were unchanged. No side effects were observed. After
      treatment, a long time lapse (about 15 weeks) was required for acid and pepsin
      secretion and gastrinemia to return to control levels, while histamine release in
      response to food normalized rapidly. Pirenzepine fixes selectively to M1
      muscarinic receptors of the synaptic ganglion, thus inhibiting the effect of
      vagal stimulation, especially on pepsin secretion. Our data suggest that it might
      also fix to M1 receptors located on ECL cells, thereby reducing histamine
      release. In addition, pirenzepine probably fixes to other muscarinic receptors
      inhibiting gastrin release and resulting in a G and secretory cell mass
      reduction, probably by increasing somatostatin release.

PMID- 8737958
TI  - Permutation distribution estimation applied to the comparison of the profile of
      the activity of two antianginal drugs.
AB  - The comparison of the anti-ischemic activity of trimetazidine and propranolol was
      evaluated by multiple end points (clinical, exercise test, and ambulatory
      electrocardiogram [ECG] monitoring criteria) in 149 male patients with effort
      angina who received either trimetazidine 20 mg tid or propranolol 40 mg tid
      during a period of 3 months. The distribution of the standardized differences
      between the two treatments for each variable was obtained by a permutation
      method. The medians (estimation of the actual difference between the two
      treatments) and the 5, 25, 75 and 95% quantiles were represented on the same
      diagram for all end points. The pattern of the standardized distribution of the
      differences showed a similar activity of both drugs on symptoms and nitrates
      consumption, on exercise tolerance and increase in ischemic threshold at
      exercise, and on ischemia recorded at ambulatory ECG monitoring. Conversely, only
      propranolol decreased heart rate and rate pressure product at rest as well as at
      exercise, underlining the difference in the mode of action of the two drugs. This
      descriptive technique is an attractive method to evaluate the differences between
      drugs considering multiple criteria favouring the estimation of these differences
      together with their variability.

PMID- 8737959
TI  - Influence of fluvoxamine on tacrine metabolism in vitro: potential implication
      for the hepatotoxicity in vivo.

PMID- 8737960
TI  - Assessment of CYP2D6 activity in very elderly healthy subjects.

PMID- 8737961
TI  - Refinement and validation of an alternative bioassay for potency testing of
      therapeutic botulinum type A toxin.
AB  - The type A neurotoxin produced by Clostridium botulinum is a potent neuromuscular
      blocking agent which causes paralysis by preventing the release of
      neurotransmitter from motor neurones. This property has led to the use of the
      toxin in the treatment of a number of neuromuscular diseases involving muscle
      spasms. At present, the only recognised assay with the specificity and
      sensitivity to estimate accurately the potency of botulinum toxin in clinical
      preparations is bioassay, in which lethality is used as the end point. Refinement
      of this assay, with respect to the end point, was explored on the basis of the
      development of flaccid paralysis of muscles following subcutaneous injection of
      the toxin at the inguinocrural region. Potency estimates, relative to in house
      reference preparations, for different therapeutic preparations obtained using
      flaccid paralysis as a scored response gave excellent agreement with estimates
      obtained in independent assay using the currently required control method. This
      study demonstrates that an alternative, more humane bioassay for potency testing
      of clostridia neurotoxins gives valid estimates equivalent to those currently in
      use.

PMID- 8737962
TI  - Aluminium accumulation in some tissues of rats with compromised kidney function
      induced by cadmium-metallothionein.
AB  - Two experiments (I and II) were performed to study aluminium accumulation in
      brain as well as in several other tissues in male Wistar rats. A single
      intraperitoneal injection of cadmium-metallothionein (CdMT, 0.1-0.4 mg Cd/kg
      b.wt.) was used to compromise kidney function 12 hr before the final aluminium
      injection in both experiments. In experiment I, rats were maintained on diets
      deficient (0.01%, w/w) in calcium (-Ca) or providing adequate (+Ca) dietary
      calcium (0.9%) for 6 weeks. Among animals given a daily intraperitoneal dose of
      aluminium chloride (10.8 mg Al/kg per day) on 6 consecutive days there was a
      tendency towards higher aluminium level in brains of rats with compromised kidney
      function from CdMT (in -Ca rats: the geometric mean [G] = 288 versus 205 ng/g wet
      weight [w., wt.], P = 0.07, and in +Ca rats: G = 242 versus 164, P < 0.05) as
      compared to animals given no CdMT. The results from experiment II (all rats were
      given aluminium 5.6 mg Al/kg 2 and 12 hr after CdMT injection) demonstrated a
      higher level of aluminium (G: 41 ng/g w. wt., P < 0.05) in brains of rats with
      only slightly damaged kidney function (0.1 mg Cd/kg) than in those given no CdMT
      (G: 29 ng/g w. wt.). It was also observed that 1) calcium deficiency had a
      statistically significant effect (P < 0.05) in increasing kidney retention of
      intraperitoneal aluminium (G: 327 micrograms/g w. wt.) as compared to rats with a
      normal calcium supply in the diet (G: 54 micrograms/g w. wt.); 2) when aluminium
      concentration in kidney was at and above 54 micrograms/g wet tissue, kidney
      damage was observed. The above results indicate that compromised kidney function
      including tubular damage induced by a low-dose of CdMT may play a crucial role in
      the accumulation of aluminium in brain and other tissues. Since tubular function
      decreases with age in human populations, these findings in rats may be of
      considerable importance if a similar phenomenon would occur in humans. Therefore,
      the possibility of increased aluminium retention in persons with low calcium and
      high aluminium intakes may need to be further investigated.

PMID- 8737963
TI  - The sigma ligand JO 1784 prevents trimethyltin-induced behavioural and sigma
      receptor dysfunction in the rat.
AB  - Recently much research interest has focused on the possible therapeutic uses of
      sigma-receptor ligands in psychiatric and neurodegenerative disorders. In the
      present study, the potential neuroprotective effects of chronic (52 days)
      administration of (+) cinnamyl-l-phenyl-l-N-methyl-N-cyclo propylene (JO 1784) (1
      and 3 mg/kg subcutaneously), a potent and selective sigma receptor ligand, were
      assessed in the trimethyltin (8 mg/kg intraperitoneally) model of memory
      dysfunction. JO 1784 (3 mg/kg subcutaneously) prevented the trimethyltin-induced
      deficits in locomotor activity, passive avoidance and radial maze performance,
      while the lower dose of JO 1784 had little or no effect. Trimethyltin was also
      shown to produce a marked reduction in the binding of [3H] (+)-pentazocine to
      sigma-receptor sites in limbic brain structures, as detected by quantitative
      autoradiography, which was particularly evident in the hippocampal pyramidal
      cells. JO 1784 (3 mg/kg subcutaneously) successfully attenuated this loss of [3H]
      (+)-pentazocine binding sites in the hippocampus (CA1, CA3 and CA4 regions) and
      in the substantia innominata. This neuroprotective effect of JO 1784 in the
      trimethyltin model would seem to be related to the modulatory effects of this
      sigma ligand on trimethyltin-induced glutamate neurotoxicity.

PMID- 8737964
TI  - Debrisoquin and S-mephenytoin hydroxylation phenotypes and CYP2D6 genotypes in an
      Estonian population.
AB  - The polymorphisms of debrisoquin (CYP2D6) and S-mephenytoin (CYP2C19)
      hydroxylation were studied in 210 unrelated healthy native Estonians by
      coadministration of mephenytoin and debrisoquin or dextromethorphan. Among the
      210 volunteers 21 (10%) were poor metabolizers of debrisoquin/dextromethorphan
      and two (0.95%) were poor metabolizers of S-mephenytoin. By pooling these data
      with an earlier study on 156 Estonians, the prevalences of poor metabolizers of
      debrisoquin/dextromethorphan and poor metabolizers of S-mephenytoin were 7.6% and
      2.2%, respectively. The CYP2D6 genotype of 151 subjects was analysed by allele
      specific PCR amplification for the defect alleles CYP2D6A and CYP2D6B. All poor
      metabolizers of debrisoquin carried two defect CYP2D6-alleles. The phenotype
      (extensive or poor metabolizer) was in all subjects correctly predicted by the
      genotype. The frequencies of the defect alleles CYP2D6B and CYP2D6A among these
      151 subjects (including 14 poor metabolizers-9.3%) were 21.5% and 2.3%,
      respectively. DNA from 6 subjects with very high CYP2D6 activity (debrisoquin MR
      < 0.1) was analysed by EcoRI RFLP to identify duplicated or amplified CYP2D6
      genes. Two of the subjects were found to carry a duplicated CYP2D6L-gene. In
      conclusion, the distribution of genetically determined metabolic capacities of
      CYP2D6 and CYP2C19 in Estonian unrelated subjects did not differ significantly
      from that in other Caucasian populations. The CYP2D6 phenotype was predicted by
      PCR-based amplification for the CYP2D6A and CYP2D6B-alleles.

PMID- 8737965
TI  - Tissue changes in glutathione metabolism and lipid peroxidation induced by
      swimming are partially prevented by melatonin.
AB  - The present study used male Sprague-Dawley rats to investigate changes in
      glutathione [reduced (GSH) and oxidized GSH (GSSG)]. lipid peroxidation (as
      indicated by tissue levels of malonaldehyde and 4-hydroxyalkenals), and the
      activity of the antioxidant enzyme glutathione peroxidase after a bout of
      swimming (30 min.) with or without melatonin (N-acetyl-5-methoxytryptamine)
      treatment. In muscle, the concentration of GSH and the GSH/GSSG ratio were
      decreased following 30 min. of swimming: these changes are indicative of enhanced
      oxidative stress. Pretreatment with melatonin prevented these effects. In liver,
      swimming increased significantly both GSH and GSSG, and decreased the GSH/GSSG
      ratio. When animals were treated with melatonin, concentrations of GSH and GSSG
      were also increased after swimming: however, the reduction in the GSH/GSSG ratio
      was prevented by melatonin. Brain GSH/GSSG ratio was not affected by exercise or
      by melatonin. Swimming enhanced the levels of lipid peroxidation products is
      muscle: this was prevented in animals treated with melatonin. Glutathione
      peroxidase activity was significantly elevated after swimming in both liver and
      brain with the change not being influenced by concurrent melatonin treatment. It
      is concluded that swimming imposes an oxidative stress on liver and skeletal
      muscle and the results show that melatonin confers partial protection against
      oxidative toxicity, especially in muscle.

PMID- 8737966
TI  - Effect of picrotoxin on antinociception in the formalin test.
AB  - Subcutaneous injection of diluted formalin (0.25 microliter of 0.5%) caused a
      biphasic pain response in mice. The first phase of pain was observed during the
      first 5 min., while the second phase occurred 10-30 min. after formalin
      administration. With the formalin test, it was found that the antinociception
      produced by the GABA-A antagonist, picrotoxin, and the GABA-B antagonist,
      phaclofen, was abolished when employed in combination. The opioid antagonist
      naloxone and antimuscarinic atropine also decreased the picrotoxin response.
      However, sulpiride, SCH 23390, phenoxybenzamine and propranolol did not alter the
      picrotoxin response. Administration of naloxone, sulpiride and propranolol showed
      a pain response. The data indicate that dopaminergic and adrenergic mechanisms
      may not be involved in the picrotoxin antinociceptive effect. However,
      postsynaptic GABA-A and GABA-B may be involved in the drug effect, and
      involvement of opioid or cholinergic systems can not be excluded.

PMID- 8737967
TI  - 5-HT3 receptor antagonist MDL 72222 dose-dependently attenuates cocaine- and
      amphetamine-induced elevations of extracellular dopamine in the nucleus accumbens
      and the dorsal striatum.
AB  - The effects of a 5-HT3 receptor antagonist MDL 72222 on cocaine- and amphetamine
      induced increases in extracellular dopamine in the nucleus accumbens and the
      dorsal striatum were studied with microdialysis technique using halothane
      anaesthesized rats. Dopamine and its metabolites were measured by HPLC with
      electrochemical detection. Cocaine elevated extracellular dopamine in the nucleus
      accumbens and to a lesser extent in the dorsal striatum, but it did not affect
      dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic
      acid. Pretreatment with MDL 72222 (25-100 micrograms/kg) dose-dependently
      attenuated cocaine-induced elevation of dopamine in both of the nuclei studied.
      Amphetamine elevated extracellular dopamine and reduced DOPAC and homovanillic
      acid equally in the nucleus accumbens and in the dorsal striatum. MDL 72222 also
      attenuated the amphetamine-induced elevation of extracellular dopamine
      concentration in both brain areas studied, but first at a dose of 100
      micrograms/kg. The different potencies of the interactions of the 5-HT3 receptor
      antagonist with cocaine and amphetamine could be related to the different
      mechanisms by which these drugs primarily elevate extracellular dopamine.

PMID- 8737968
TI  - Differential effects of morphine-6-glucuronide, an active metabolite of morphine,
      and morphine on locomotor activity in mice: involvement of the opioid receptor.
AB  - Subcutaneous administration of morphine (2.5 to 20 mg/kg) or an active metabolite
      of morphine, morphine-6-glucuronide (2.5 to 20 mg/kg), increased the locomotor
      activity of mice in a dose-dependent manner. Fifteen mg/kg of morphine and 20
      mg/kg of morphine-6-glucuronide were almost equipotent. Subcutaneous
      administration of the universal opioid antagonist, naloxone, but not the delta
      selective antagonist, naltrindole, significantly suppressed the hyperlocomotion
      induced by morphine (15 mg kg). On the other hand the subcutaneous administration
      of relatively higher doses of naloxone or naltrindole significantly reduced the
      hyperlocomotion induced by morphine-6-glucuronide (20 mg/kg). These findings
      suggest that agonistic actions at the opioid receptors, especially at the delta-
      and mu-receptors, contribute to the morphine-6-glucuronide-induced
      hyperlocomotion.

PMID- 8737969
TI  - Capsaicin-, resiniferatoxin-, and lactic acid-evoked vascular effects in the pig
      nasal mucosa in vivo with reference to characterization of the vanilloid
      receptor.
AB  - Nasal cavity volume, mucosal and superficial skin blood flow as well as renal
      splenic vascular effects of capsaicin, resiniferatoxin and lactic acid were
      investigated, using a novel in vivo pig model. The present results show that
      locally intraarterially injected capsaicin, resiniferatoxin and lactic acid evoke
      similar vasodilatory responses, although with different duration, in the nasal
      mucosa and superficial skin as well as an increase in heart rate and mean
      arterial blood pressure. Nasal vascular responses evoked by capsaicin,
      resiniferatoxin and lactic acid were unaffected by the cyclooxygenase inhibitor
      diclofenac. Moreover, chlorisondamine did not alter the nasal vasodilatory
      responses evoked by capsaicin and lactic acid. However, chlorisondamine abolished
      sympathetic reflex-mediated vasoconstrictor effects of capsaicin in the spleen
      and kidney. Lactic acid-evoked vasodilation in the nasal mucosa and skin was
      inhibited by the 8-37 fragment of calcitonin gene-related peptide, a calcitonin
      gene-related peptide-receptor antagonist. Lactic acid-evoked vasoconstriction in
      the spleen and kidney was reduced but not abolished by chlorisondamine,
      suggesting that the effects of lactic acid are not exclusively reflex-mediated.
      Capsazepine did not inhibit the vasodilatation in the nasal mucosa evoked by
      capsaicin and lactic acid. [3H]Resiniferatoxin bound to pig nasal mucosa
      membranes with an affinity of 134 pM in a non-cooperative fashion; this binding
      behaviour contrasted to the apparent positive cooperativity (a Hill coefficient
      of 2.2) of specific resiniferatoxin binding to pig spinal cord preparations.
      Specific [3H]resiniferatoxin binding to nasal mucosa membranes was fully
      inhibited by capsaicin (Ki = 5 microM) and lactic acid (IC50 at pH 5.0) but not
      by capsazepine (up to 10 microM), in accord with the physiological findings.
      Capsazepine, by contrast, displaced [3H]resiniferatoxin from spinal vanilloid
      receptors with an affinity of 3 microM. These findings show the presence of
      vanilloid receptors in the pig nasal mucosa and suggest heterogeneity in the
      properties of vanilloid receptors in the pig. Furthermore, lactic acid evokes
      vascular effects similar to those of capsaicin and resiniferatoxin, possibly via
      interaction of protons and/or proton-generated substances at vanilloid receptors
      with a subsequent release of calcitonin gene-related peptide.

PMID- 8737970
TI  - The influence of ammonium persulfate on guinea pig tracheal muscle tone: release
      of nitric oxide.
AB  - Clinical studies have shown that oxidizing substances like hydrogen peroxide
      (H2O2) and ammonium persulfate used in the hair cosmetic industry may cause
      airway diseases. In in vitro experiments with isolated guinea pig tracheae
      ammonium persulfate solutions induced an initial transient relaxation of smooth
      muscles. This relaxation could be measured by a decrease in isometric pressure in
      the cannulated trachea instilled with ammonium persulfate at a hydrostatic
      pressure of 2.5 kPa. In control experiments, saline caused an initial pressure
      decrease of less than 10% within one minute. In contrast, instillation of
      different ammonium persulfate solutions (9.10(-5) to 9.10(-2) M) effectively
      dilated tracheae and resulted in a concentration-dependent drop in intratracheal
      pressure to 1.53 +/- 0.62 kPa (61% of the instillation pressure). The effect of
      ammonium persulfate on smooth muscles is obviously mediated by nitric oxide
      because the relaxation could be blocked by inhibitors of nitric oxide synthase (L
      NMMA 40 microM and L-NAME 200 microM). The precursor of nitric oxide, L-arginine
      (1 mM), the D-isomers of the inhibitors and a mixture of L-arginine and L-NAME
      did not affect the ammonium persulfate-induced initial intratracheal pressure
      decrease. The results allow us to conclude that acutely elicited tracheal muscle
      dilatation by ammonium persulfate is mediated by nitric oxide. However, it is
      possible that a continuous use of oxidizing substances may lead to epithelial
      damage and, therefore, reduce the production of nitric oxide, thus facilitating
      constrictory responses.

PMID- 8737971
TI  - Effects on behaviour and EEG of single chain phospholipases A2 from snake and bee
      venoms injected into rat brain: search for a functional antagonism.
AB  - Three phospholipase A2 (PLA2s), OS1 and OS1 purified from the taipan snake venom
      Oxyuranus scutellatus scutellatus and bee venom PLA2 were injected to rats by the
      intracerebroventricular route. OS1 showed no sign of neurotoxicity at doses at
      which OS2 and bee venom PLA2 produced multiform dose-dependent behavioural
      effects including motor disturbances (stereotyped movements), compulsive
      scratching, convulsions and breathing difficulties. EEG recordings showed at the
      very time when the animal was motionless the induction of several episodes of a
      low frequency hippocampal theta rhythm, index of long-term changes in synaptic
      neuroplasticity. Spike-wave discharges were also produced but the occurrence was
      not systematic. These seizures were often accompanied with behavioural
      convulsions. Blockers of NMDA receptors and drugs modifying the GABAergic
      transmission could not abolish the neurotoxic effects of PLA2s except for
      diazepam (10 mg/kg intraperitoneally) that prevented only OS2-induced
      disturbances. Blockers of L-type Ca2+ channels and K+ channel openers were also
      without effect. The toxicity of OS2 and bee venom PLA2 is probably due to their
      initial specific binding to their neuronal receptor sites.

PMID- 8737972
TI  - Pharmacokinetic-pharmacodynamic modelling of zopiclone effects on human central
      nervous system.
AB  - The present data shows the pharmacokinetics and concentration-effect relationship
      of a single 7.5 mg oral dose of zopiclone in ten healthy volunteers. Plasma
      concentrations and effects of zopiclone on central nervous system as quantified
      by changes in saccadic peak velocity and digit symbol substitution test were
      measured for 17 hr after ingestion of zopiclone. Pharmacokinetics was described
      with a linear one-compartment open model. Maximum effects preceded peak plasma
      zopiclone concentrations causing a clockwise hysteresis, i.e. proteresis, in
      concentration versus effect loops. Therefore, pharmacodynamics was described both
      with a tolerance model and a model with distributional pseudo-tolerance where the
      concentration in the blood sampling site is assumed to equilibrate slower with
      arterial blood than the site of action of zopiclone. Both models related the
      changes in pharmacodynamics linearly to changes in zopiclone concentrations. The
      median (range) values for clearance, volume of distribution and elimination half
      life were 21 (15-53) L/hr, 132 (58-161) L and 3.4 (1.7-5.7) hr, respectively.
      Both pharmacodynamic models were able to describe the relationship between
      zopiclone concentrations and changes in psychomotor performance equally well.
      However, because the pharmacodynamics of zopiclone were studied in a non-steady
      state situation, the mechanism for proteresis, i.e. true tolerance versus
      distributional pseudotolerance cannot be identified.

PMID- 8737973
TI  - Neurochemical mediators of anxiety have inconsistent effects on hypothalamic self
      stimulation in rats.
AB  - We studied effects of anxiogenic and anxiolytic compounds on the electric self
      stimulation of the medial fore-brain bundle in male rats to find out if there is
      a link between reward and anxiety-related behaviours. The cholecystokinin
      agonist, caerulein (25-100 micrograms/kg) and the 5-HT agonist 1-(3
      chlorophenyl)piperazine (0.2-1 mg/kg) dose-dependently inhibited the electric
      self-stimulation. The 5-HT2A antagonist, ketanserin, at 2.5 mg/kg, increased the
      self-stimulation at high currents but not at threshold current. The 5-HT3
      antagonist ondansetron (10 and 100 micrograms/kg). The alpha 1-adrenergic
      antagonist, prazosin (0.125 and 0.5 mg/kg), the beta-adrenergic antagonist,
      propranolol (5 and 10 mg/kg) and the alpha 2-adreno-receptor antagonist,
      atipamezole (4 mg/kg), did not affect the self-stimulation. Nor did the
      benzodiazepine agonist, diazepam (5-15 mg/kg), a benzodiazepine receptor
      antagonist flumazenil (at 10 and 25 mg/kg) or the inverse agonist of
      benzodiazepine receptors, N-methyl-beta-carboline-3-carboxamide (10 and 20
      mg/kg), cause any substantial changes of the self-stimulation. We conclude that
      only two anxiolytic drugs (caerulein and 1-(3-chlorophenyl)piperazine) suppress
      the electric self-stimulation. These findings indicate that anxiogenicity as such
      is not able to weaken the hypothalamic electric self-stimulation. Anxiety and
      reward are apparently mediated through separate neural pathways.

PMID- 8737974
TI  - Gaucher disease: studies of phenotype, molecular diagnosis and treatment.
AB  - This report summarizes the results on 39 patients with Gaucher disease who have
      been genotyped, evaluated, and/or followed at this center. Mutation analysis for
      4 common mutations; N370S, L444P, 84gg and IVS2 (+1), was performed for all
      patients. Mutation analysis identified both mutant alleles in 69% and at least
      one mutant allele in 90% of all chromosomes. This study group of 39 patients
      included 32 type 1, four type 2 and three type 3 patients. We include the details
      of the clinical course of two patients with Gaucher disease treated with enzyme
      replacement therapy (ERT). One patient with chronic neuronopathic Gaucher disease
      has been treated with enzyme replacement therapy (ERT) at a dose of 60 U/kg every
      2 weeks since 2.5 years of age and has shown no progression of neurologic
      involvement. A second patient with non-neuronopathic Gaucher disease has
      demonstrated an unusually delayed response to ERT. No clinical response was noted
      following 17 months of treatment at 60 U/kg every 2 weeks. Only after the dose
      was increased to 60 U/kg every week was a clinical response evident. Response to
      treatment at 15 U/kg every 2 weeks was variable in the four type 1 patients
      treated at the lower dose. In two of these patients with identical genotypes, one
      patient demonstrated a positive clinical response to low dose treatment while the
      other patient did not.

PMID- 8737976
TI  - Rothmund-Thomson syndrome in siblings: evidence for acquired in vivo mosaicism.
AB  - Rothmund-Thomson syndrome (RTS) is an autosomal recessive disorder characterized
      by skin abnormalities that appear in infancy, skeletal abnormalities, juvenile
      cataracts and other manifestations of premature aging, and a predisposition to
      malignancy. The diagnosis is made on clinical grounds as no consistent laboratory
      test has been identified. Chromosome studies have been reported for only three
      patients with RTS and in two of these three, trisomy 8 mosaicism was found. We
      performed a variety of cytogenetic and molecular genetic studies on two siblings
      with RTS and on their phenotypically normal parents. Two chromosomally abnormal
      clones involving either trisomy 8 or i(8q) were found in both patients with RTS.
      These clones were present in vivo, as they were seen in interphase buccal smears
      and lymphocytes from unstimulated preparations using both conventional
      cytogenetic studies and fluorescence in situ hybridization (FISH) with a
      centromere probe for chromosome 8. These results suggest that RTS is associated
      with in vivo clonal chromosomal rearrangements causing an acquired somatic
      mosaicism.

PMID- 8737975
TI  - Mutational screening of APP gene in patients with early-onset Alzheimer disease
      utilizing mismatched PCR-RFLP.
AB  - To elucidate the frequency of mutations of the beta/A4 amyloid protein precursor
      (APP) gene in early-onset Alzheimer disease, we designed a mismatched PCR-RFLP
      that can identify all kinds of missense mutations at codon 717 in addition to the
      seven kinds of known mutations at exon 17. When we screened mutations at exon 17
      utilizing this method and the double missense mutations at exon 16 of the APP
      gene by PCR-RFLP, no cases revealed mutations of the APP gene among 13 familial
      and 54 sporadic cases, except one family (OS-1) that had previously been reported
      and used as a positive control of APP717(Val-->Ile). Our results support the
      hypothesis that mutations in the APP gene are not major causes in early-onset
      Alzheimer disease.

PMID- 8737977
TI  - Urticaria, arthralgia, and nephropathy without amyloidosis: another variant of
      the Muckle-Wells syndrome?
AB  - The term Muckle-Wells syndrome (MWS) describes an autosomal dominant disorder
      characterised by various combinations of urticaria, sensorineural deafness,
      amyloidosis, arthralgia and skeletal abnormalities. We describe a family with
      nephropathy and several symptoms of MWS, but no evidence of deafness or
      amyloidosis. Since nephropathy without amyloidosis has never been reported in
      MWS, but deafness is a feature of all reported pedigrees, we conclude that
      members of this family have a previously unreported inherited predisposition to
      urticaria, arthralgia and nephropathy which is distinct from the MWS phenotype.

PMID- 8737979
TI  - Maternal non-recognition of Down syndrome in black South African infants.
AB  - Down syndrome (DS), one of the commonest causes of mental retardation in
      Caucasoids, has only rarely been described in Africa. In previous studies it was
      suggested that there may be clinical difficulties in making the diagnosis in
      African neonates. In the present study data were collected by means of a
      questionnaire administered partly before and partly after a genetic counselling
      session, to 35 mothers of African infants with DS. The results show that 83% of
      these mothers did not recognise any facial difference between their affected
      infant and other normal infants and 57% did not observe any other physical
      differences. After counselling, 40% of the sample still did not accept that their
      infant was different from other newborns. Only one mother was aware of infants
      with similar characteristics. These findings suggest that if mothers themselves
      cannot see the differences between their DS children and normal children,
      clinical diagnosis based on physical stigmata may be difficult. Furthermore,
      acceptance of the diagnosis may be retarded until delayed mile-stones can be
      observed in the affected infants.

PMID- 8737978
TI  - Attitudes towards termination for fetal abnormality: comparisons in three
      European countries.
AB  - Attitudes towards termination for a range of genetic conditions were studied in
      health professionals and lay people in three European countries: Germany,
      Portugal and the UK. The health professionals consisted of geneticists in all
      countries and additionally obstetricians from Portugal and the UK. The lay
      persons consisted of pregnant women, and male and female non-medical university
      employees. In all, more than 1,700 study participants completed questionnaires.
      Overall, health professionals were more likely than the lay persons to report
      that they would opt for termination following diagnosis of a fetal abnormality.
      Differences were found between countries and study groups. German respondents
      were least likely to report that they would undergo termination in the case of a
      fetal abnormality while Portuguese respondents were most likely to report that
      they would undergo a termination. Further studies are needed to determine first
      the extent to which differences between health professionals and lay samples
      reflect a difference in perception of disability, including tolerance of having a
      child with a disability; and second, whether such differences result in health
      professionals presenting termination of pregnancy in a way that is not concordant
      with patients' value systems.

PMID- 8737980
TI  - Risk estimates for balanced reciprocal translocation carriers--prenatal diagnosis
      experience.
AB  - An analysis was performed on 40 families at risk for an unbalanced rearrangement
      in the fetus because one of the parents is a reciprocal translocation carrier.
      The overall risk at second trimester prenatal diagnosis was 14% (8/57). The
      individual risk for unbalanced offspring at second trimester prenatal diagnoses
      and at birth were estimated using empirical data by Stengel-Rutkowski et al.
      (1988). The risks at birth ranged from 0%-21.6%. Most reciprocal translocations
      (22 or 55%) were at low risk. Without risk (7 or 17.5%), medium risk (6 or 15%)
      and high risk (5 or 12.5%) translocations were about equally represented and
      relatively infrequent. The analysis shows that the mode of ascertainment as well
      as the measurement of lengths of observed or probable imbalances cannot serve as
      a reliable risk predictor in individual counselling. In the translocations
      ascertained through spontaneous abortions the risk is frequently small or
      nonexistent, but remarkable exceptions to this rule are observed. Translocations
      discovered through unbalanced offspring were found to belong to different risk
      groups with the exception of the no risk group. Individual risk estimates have to
      be performed as a basis of genetic counselling before or during pregnancy so that
      parents with reciprocal translocations can make their choices regarding the
      available options.

PMID- 8737981
TI  - Wolcott-Rallison syndrome associated with congenital malformations and a mosaic
      deletion 15q 11-12.
AB  - Wolcott-Rallison syndrome is a rare autosomal recessive condition first described
      in 1972. It is characterised by diabetes mellitus which arises in early infancy
      and multiple epiphyseal dysplasia. We describe an affected girl who had recurrent
      episodes of hepatic failure for which no obvious cause was found. Post-mortem
      examination revealed abnormal pancreatic histology and congenital abnormalities
      of the central nervous and cardio-respiratory systems which have not been
      previously described in this condition. She also demonstrated a deletion at 15q
      11-12 in 65% of her cells.

PMID- 8737982
TI  - Jumping translocation in a phenotypically normal female.
AB  - "Jumping translocation" jt refers to a rare type of chromosome mosaic, in which
      the same portion of a (donor) chromosome is translocated to different (recipient)
      chromosome sites. Jt have mainly been observed in lymphocyte cultures of patients
      with hematologic malignancies. We report a phenotypically normal female carrying
      a mosaic of two cell lines with the Xq26-qter segment translocated to the short
      arm of chromosomes 15 or 21 in peripheral blood lymphocytes. In skin fibroblasts,
      only the X/21 translocation was detected. We speculate that recombination between
      homologous repetitive sequences on non-homologous human acrocentrics may be the
      cause of such chromosomal rearrangements.

PMID- 8737983
TI  - Benign external hydrocephalus in a boy with autosomal dominant microcephaly.
AB  - In a 3-month-old boy with microcephaly, magnetic resonance imaging (MRI) revealed
      accumulation of bifrontal extracerebral fluid. Because of the typical MRI
      findings and the disappearance of these findings later on, he was diagnosed as a
      case of benign external hydrocephalus. Both his mother and maternal grandmother
      had microcephaly, without neurological or dysmorphic manifestations. The pedigree
      is most consistent with an autosomal dominantly inherited microcephaly. This
      seems to be the first report of benign external hydrocephalus found in a patient
      with an autosomal dominant microcephaly.

PMID- 8737984
TI  - An AvaII polymorphism in the human apolipoprotein C-II gene.

PMID- 8737985
TI  - Detection of a SacI restriction fragment length polymorphism at the human
      phenolsulphotransferase locus.

PMID- 8737986
TI  - Generation and characterization of inducible nitric oxide synthase deficient
      macrophage cell lines.
AB  - Stable inducible nitric oxide synthase deficient mouse macrophage cell lines were
      generated by the antisense technology. A 666 bp fragment of a mouse inducible
      nitric oxide synthase cDNA was cloned in antisense orientation into a mammalian
      expression vector behind the CMV promoter. This construct was transfected into
      J774.1A cells, a mouse macrophage cell line. The inducible nitric oxide synthase
      antisense lines showed up to 84% reduction of nitric oxide production in response
      to lipopolysaccharide stimulation and 66% reduction of nitric oxide production in
      response to interferon-gamma and a combination of interferon-gamma and
      lipopolysaccharide stimulation. The deficiency in inducible nitric oxide synthase
      expression had no impact on lipopolysaccharide induced tumor necrosis factor
      alpha and interleukin-1 secretion. The stable and specific inhibition of
      inducible nitric oxide synthase expression by antisense DNA vectors allows a
      direct analysis of contribution of inducible nitric oxide synthase activity to
      macrophage regulatory and immune defence functions.

PMID- 8737987
TI  - Pathogenic mechanisms induced by microbial proteases in microbial infections.
AB  - Most bacterial and fungal proteases excreted into infected hosts exhibit a wide
      range of pathogenic potentials ranging from pain, edema or even shock to
      translocation of bacteria from the site of infection into systemic circulation,
      thus resulting in septicemia. The basic mechanism or principle common to all
      these phenomena is explained by kinin generation, either directly from high-
      and/or low-molecular weight kininogens or indirectly via activation of the
      bradykinin generating cascade: i.e. Hageman factor-->activated Hageman factor-
      >prekallikrein-->kallikrein-->high-molecular weight kininogen-->bradykinin. Some
      bacterial proteases are also involved in activation of other host protease
      zymogens such as plasminogen, procollagenase (matrix metallo proteases) and
      proenzymes of the clotting system. Furthermore, most bacterial proteases are not
      only resistant to plasma protease inhibitors of the hosts, most of which belong
      to a group of serine protease inhibitors called serpins (serine protease
      inhibitors), but they also quickly inactivate serpins. Some bacterial proteases
      may also activate bacterial toxins thus rendering toxigenic pathogenesis. They
      are also capable of degrading immunoglobulins and components of the complement
      system and facilitate propagation of micro organisms. All in all, microbial
      proteases are very critical in enhancing pathogenesis of severe diseases. It is
      also noteworthy that bacterial cell wall components themselves, i.e. endotoxin
      (or lipopolysaccharide) of gram negative bacteria and teichoic/lipoteichoic acid
      of gram positive bacteria, are also able to activate the bradykinin generating
      cascade-involving activation of Hageman factor as mentioned above.

PMID- 8737989
TI  - Dramatic changes in the ratio of homologous recombination to nonhomologous DNA
      end joining in oocytes and early embryos of Xenopus laevis.
AB  - We have developed a versatile plasmid vector (pReco-sigma) for recombination
      studies. When linearized and introduced into the cells of interest, pReco-sigma
      allows the simultaneous determination of the relative frequencies of homologous
      recombination versus nonhomologous DNA-end joining (also termed end-to-end
      joining), the latter an example of illegitimate recombination processes. As a
      system we made use of stage VI oocytes and fertilized eggs of the African clawed
      frog Xenopus laevis, which were previously described to support homologous
      recombination and DNA-end joining, respectively. Extending these earlier
      findings, we show that oocytes yield > 80% of the homologously recombined
      product, whereas in eggs a highly efficient DNA-end joining activity predominates
      (> 95%). Both reactions, homologous recombination and DNA-end joining, are shown
      to occur quickly, with the majority of the respective products being formed
      within the first 20 minutes of incubation under optimal conditions. In fertilized
      eggs, up to 50% of all injected linear DNA molecules are recircularized by DNA
      end joining. With high amounts of injected DNA per fertilized egg, DNA-end
      joining is reduced, presumably due to competition for essential factors, and
      homologous recombination becomes readily detectable. As there is a sequence of
      rapid cleavage divisions after fertilization of the egg, the fast and highly
      efficient DNA-end joining, even though it is error-prone at the junction site,
      seems to be best suited to cope with DNA double-strand breaks that might occur in
      the genome during early embryogenesis. On the other hand, the long-lived oocytes
      seem to repair DNA double-strand breaks via homologous recombination. This latter
      property may be exploited both in Xenopus and in other organisms to achieve
      homologous integration of exogenous DNA into germ cells for gene targeting.

PMID- 8737988
TI  - Putrescine active uptake system in the Trypanosomatid Crithidia fasciculata.
AB  - Using the insect Trypanosomatid Crithidia fasciculata as a model parasite of
      mammalian pathogenic flagellates, i.e. Leishmania and Trypanosoma spp., we have
      studied the kinetic and regulatory characteristics of the polyamine uptake
      system. Putrescine transport was age-dependent with maximum expression values at
      the proliferative logarithmic phase. Putrescine transport in Crithidia
      fasciculata was energy-dependent and against a putrescine concentration gradient.
      The integrity of the membrane sulfhydryl groups was absolutely required for
      optimum transport rates. The specificity of this mechanism was studied in the
      presence of a series of different chain length aliphatic diamines, showing the
      high specificity for putrescine and the poor effect of this series at the highest
      concentration analyzed as well as the higher polyamines spermidine and spermine.
      Finally, the well-known inhibitor of polyamine biosynthesis, DFMO, led to an
      upward regulation of putrescine uptake correlating with the depletion of
      intracellular polyamine pool. In addition, the presence of high concentrations of
      putrescine in the culture medium produced a downward regulation of this system.

PMID- 8737990
TI  - The rps4-gene is encoded upstream of the nad2-gene in Arabidopsis mitochondria.
AB  - In Arabidopsis mitochondria the nad2-gene consists of five exons (a-e) which are
      separated by three cis-splicing introns and one trans-splicing intron. Sequence
      analysis of the region upstream of exons a and b reveals an open reading frame
      encoding ribosomal protein S4 (rps4). In the second nad2 coding region (exons c
      e) a pseudo tRNA(Tyr) sequence and a fragment of the plastid psbA gene are
      located upstream of the trans-spliced exon c. Primer extension analysis
      identifies RNA 5'-termini within the pseudo-tRNA(Tyr) confirming this sequence to
      be non-functional. Northern blot analysis suggests the rps4-gene to be
      cotranscribed with at least the first part of the nad2-gene. The rps4 and nad2
      coding sequences as well as the first cis-intron and the trans-intron sequences
      of the nad2 gene are altered by RNA editing. RNA editing in the open reading
      frames improves in most instances conservation of the specified amino acids.

PMID- 8737991
TI  - Synthetic peptides corresponding to alpha-lactalbumin and beta-lactoglobulin
      sequences with angiotensin-I-converting enzyme inhibitory activity.
AB  - Novel angiotensin-I-converting enzyme (ACE) inhibitory activities were detected
      in synthetic peptides corresponding to sequences of beta-lactoglobulin and alpha
      lactalbumin and which are known to possess opioid activity. Using hippuryl
      histidyl-leucine as substrate, the tetrapeptides beta-lactorphin (Tyr-Leu-Leu
      Phe), alpha-lactorphin (Tyr-Gly-Leu-Phe) and beta-lactotensin (His-Ile-Arg-Leu)
      were shown to have IC50 values of 171.8, 733.3 and 1153.2 microM, respectively.
      Related dipeptides also inhibited ACE, with Tyr-Leu being the most potent, having
      an IC50 value of 122.1 microM.

PMID- 8737992
TI  - The structures of the bovine and porcine proacrosin genes and their conservation
      among mammals.
AB  - Sperm acrosin is a serine protease that is involved in the recognition, binding
      and penetration of the sperm of the zona pellucida of the ovum. The bovine and
      porcine genes were cloned and characterized. Alignment of the intron/exon
      structure of both genes with the previously characterized human, rat and mouse
      genes and with other serine protease genes reveals that the coded sequence of the
      mammalian proacrosin is distributed in 5 exons and the splice junction types are
      identical to the exons encoding the catalytic domain of other serine protease
      genes. A comparison of the bovine, porcine, human, guinea pig, rabbit, rat and
      mouse preproprotein sequences shows that the catalytic domain is highly
      conserved, while the sequence of the proline rich domain is very variable among
      the species, ranging from 28.9% to 68.8%.

PMID- 8737993
TI  - MRI of posterior knee masses.
AB  - A wide variety of masses may be visualized in the posterior knee. Some are
      encountered incidentally on MRI obtained for seemingly unrelated symptoms; others
      are palpable and present for MRI characterization. We describe the appearance,
      significance and pathophysiology of some of the most common lesions found in the
      popliteal fossa as well as several of the less common entities we have
      encountered. Thorough understanding of the appearance and location of the more
      specific masses should augment precise diagnosis in a majority of cases. In turn,
      this will eliminate unnecessary additional investigations and enable prompt and
      appropriate treatment.

PMID- 8737994
TI  - Longitudinal stress fractures of the tibia: diagnosis by magnetic resonance
      imaging.
AB  - OBJECTIVE: Previous works describe magnetic resonance (MR) imaging
      characteristics of stress fractures. Diagnosis of the atypical, longitudinal type
      of stress fracture has been reported using computed tomography (CT). This report
      focuses on MR imaging of longitudinal stress fractures of the tibia. MATERIALS
      AND METHODS: Six cases are presented in which a longitudinal linear abnormal
      marrow signal was detected in the middle and distal parts of the tibial shaft.
      Five patients were imaged using a 1.5 Tesla MR unit. Axial, sagittal and coronal
      T1 and T2-weighted or fat suppressed proton density fast spin echo images were
      obtained in all but one patient. One patient was imaged using a 0.5 Tesla MR unit
      with axial and coronal T1- and T2-weighted sequences. Initial conventional
      radiographs seen at clinical presentation were interpreted as normal in all
      cases. Two patients underwent radionuclide bone scan. and one patient was imaged
      with CT prior to MR imaging. RESULTS: In each instance, MR imaging demonstrated
      linear marrow signal abnormalities orientated along the long axis of the tibial
      shaft. Endosteal and periosteal callus was identified on axial images. In all
      cases, MR imaging clearly demonstrated a fracture extending through one cortex
      with abnormal signal in both the marrow cavity as well as adjacent soft tissues
      indicating edema. CONCLUSION: MR imaging was shown to be excellent for
      demonstration of fracture lines, callus, and marrow and soft tissue abnormalities
      seen in association with longitudinal stress fractures.

PMID- 8737995
TI  - Supramalleolar fatigue fractures of the tibia.
AB  - OBJECTIVE: The objective of this paper is to describe fatigue fractures in the
      supramalleolar area of the tibia. The spectrum of imaging findings in 14 cases is
      presented, with emphasis on plain film radiographic findings. DESIGN AND
      PATIENTS: Fourteen patients with fatigue fractures in the supramalleolar area of
      the distal tibia were seen in a 6-year period. The 13 men and 1 woman had an age
      range from 14 to 64 years (mean 30 years). These patients had no underlying
      conditions that would predispose them to fractures. Sequential plain film
      radiographs and other special imaging studies (technetium-99m scans and computed
      tomography) were retrospectively reviewed. RESULTS AND CONCLUSIONS: Initial plain
      film radiographs showed a horizontal linear band of increased density in only 2
      cases, a subtle cortical bulge in 5 cases, a focal "graying" of the cortex in 2
      cases, a single layer periosteal reaction in 1 case, and no abnormality in the
      final 4 cases. Technetium-99m scans were done in 11 cases and showed focal areas
      of increased uptake in all 11. These areas of increased uptake were vertically
      orientated in 10. One patient had computed tomography showing cortical thickening
      around a linear lucency. The spectrum of imaging findings is similar to that seen
      in fatigue fractures in more common locations. Supramalleolar fatigue fractures
      should be suspected in patients who have pain in the distal tibia even when
      initial plain film radiographs are normal. When initial radiographs are normal,
      technetium-99m scans can confirm the diagnosis.

PMID- 8737996
TI  - Patellar fatigue fractures.
AB  - Three cases of patellar fatigue fracture are reviewed. Two fractures presented
      with acute displacement and were initially thought to represent pathological
      fractures. Histological appearances in one case, and the clinical course in
      another, subsequently indicated that these were fatigue fractures. A third
      patient developed a chronic undisplaced fracture and followed the typical
      clinical course of fatigue fractures at other sites. The importance of
      recognizing patellar fatigue fractures and of differentiating spontaneously
      displaced fatigue fractures from pathological fractures is emphasized.

PMID- 8737997
TI  - Chronic recurrent multifocal osteomyelitis: an evolving clinical and radiological
      spectrum.
AB  - OBJECTIVE: To describe unusual clinical and radiological features in patients
      with chronic recurrent multifocal osteomyelitis (CRMO). DESIGN AND SUBJECTS:
      Based on radiographic and microscopic findings, three patients were prospectively
      diagnosed as having chronic recurrent multifocal osteomyelitis (CRMO). They form
      the basis of this report because of either the unusualness of the clinical
      presentation, hitherto undescribed associated diseases or the unusual age of
      presentation and sites of lesions. RESULTS: One patient developed pyoderma
      gangrenosum at the site of one of the skeletal lesions and then went on to
      develop ulcerative proctitis. A second patient presented with a soft tissue mass,
      which on MRI mimicked a sarcoma. The final patient presented with lesions in the
      wrist and phalanges of the toes at the unusual age of 38. None of the patients
      was treated with steroids or antibiotics for the skeletal lesions. Steroids were
      administered to one patient for treatment of pyoderma gangrenosum. CONCLUSIONS:
      The pattern and distribution of skeletal lesions in CRMO are well recognized in
      the pediatric age group. The unusual clinical and/or radiological features
      discussed herein suggests that this is a disease that continues to evolve with a
      broader spectrum of features than recognized.

PMID- 8737998
TI  - Skeletal coccidioidomycosis: imaging findings in 19 patients.
AB  - OBJECTIVE: The objective of this study was to describe the distribution and
      radiologic appearance of skeletal coccidioidomycosis in 19 documented cases.
      DESIGN AND PATIENTS: Medical records of 19 patients (17 men, 2 women; age range
      17-62 years, mean age 34 years) with clinically confirmed skeletal
      coccidioidomycosis were retrospectively reviewed. The patients were studied with
      plain radiography (n = 19), skeletal scintigraphy (n = 6), computed tomography
      (CT) (n = 5), and magnetic resonance imaging (MRI) (n = 1). RESULTS: Multiple
      lesions were seen in 11 of 19 patients (58%). Of a total of 46 lesions, 27 (59%)
      were described as punched-out lytic, 10 (22%) as permeative/destructive, and 9
      (17%) as involving a joint and/or disk space. Lesions were identified in almost
      every bone (with the exception of the facial bones, ulna, carpus, and fibula) and
      were most commonly found in the axial skeleton (20 of 46; 43%). CONCLUSION:
      Skeletal coccidioidomycosis is frequently multicentric and may involve almost any
      bone. The axial skeleton is the most common site of involvement. Lesions are
      usually well demarcated but may present with an ill-defined border and permeative
      type of bone destruction, especially in the spine. Joint involvement is not
      uncommon. Plain radiographs are effective in the initial evaluation of bones and
      joints, scintigraphic studies can identify disseminated disease, and CT and MRI
      are effective in determining soft tissue involvement and spinal abnormalities.

PMID- 8737999
TI  - Prevalence of muscle injury following intra-arterial chemotherapy.
AB  - OBJECTIVE: Intra-arterial chemotherapy (IAC) is frequently used as an adjuvant
      treatment for musculoskeletal tumors. Past studies have noted that IAC not only
      induces favorable effects in tumor, but may also cause muscle edema and necrosis
      in previously normal tissue, reflected as increased signal on T2-weighted scans.
      In order to evaluate the prevalence of these effects, we reviewed all patients
      receiving IAC and MRI at our institution. METHODS: Our study population consisted
      of 24 patients who underwent IAC. All subjects were studied with MRI both pre-
      and post-IAC. None of the subjects in this study underwent surgery or radiation
      therapy until after the post-IAC MRI examination. Any muscle group involved by
      the tumor or peritumoral edema on the initial scan was excluded from the study.
      Catheter position during IAC was recorded as central or peripheral. Scans were
      scored positive if muscle groups in regions remote from the tumor site
      demonstrated increased T2 signal following IAC. RESULTS: Six out of these 24
      patients (25%) were found to have positive results. A significant association was
      found between peripheral catheter position and a positive scan post-IAC (Fisher's
      exact test, P = 0.024). CONCLUSION: Because of our exclusion criteria, we are
      convinced that the finding of increased T2 signal in 25% of our patients was
      caused by IAC and represents muscle edema or necrosis. Knowledge of this post
      chemotherapy MR finding should help prevent confusion during the interpretation
      of follow-up MR examinations.

PMID- 8738000
TI  - Acetabular labral tears: contrast-enhanced MR imaging under continuous leg
      traction.
AB  - OBJECTIVE: The objective of this study was to evaluate the effects of continuous
      leg traction on contrast-enhanced MR imaging of the hip joint and to determine
      whether MR imaging under these conditions is useful for demonstrating acetabular
      labral tears. DESIGN AND PATIENTS: Nineteen hips underwent MR imaging with a T1
      weighted spin-echo sequence, followed by MR imaging under continuous leg traction
      after intravenous injection of gadolinium-DTPA. Joint fluid enhancement and
      labral contour detection were evaluated. Eleven hips had labral tears shown by
      conventional arthrography, arthroscopy and macroscopic surgical findings.
      Assessment of labral tears by MR imaging was correlated with the diagnosis based
      on these standard techniques. RESULTS AND CONCLUSIONS: Joint fluid enhancement
      was obtained in all hips at 30 min after injection. Superior and inferior labral
      surfaces were completely delineated in 1 hip on the unenhanced MR images, and in
      7 and 13 hips, respectively, on the enhanced images under traction. The enhanced
      images under traction depicted 9 of the 11 labral tears. Comparison between the
      unenhanced image and the enhanced image under traction avoided mistaking
      undercutting of the labrum for a tear in 4 hips. Contrast-enhanced MR imaging
      under traction was valuable for detecting labral tears non-invasively and without
      radiation. Follow-up examinations using this method in patients with acetabular
      dysplasia can help to clarify the natural course of labral disorders and enable
      better treatment planning.

PMID- 8738002
TI  - Accuracy of MRI patterns in evaluating anterior cruciate ligament tears.
AB  - The purpose of this study was to determine the different patterns of anterior
      cruciate ligament (ACL) tears on MRI and the prevalence and accuracy of these
      patterns. Images were obtained on high-tesla and low-tesla units and the results
      compared to determine whether field strength affects the interpretation using the
      grading system. In 172 patients who underwent knee MRI (109 knees with high-tesla
      units and 63 knees with low-tesla units) and arthroscopy, there was a total of 91
      arthroscopically proven ACL tears. Five patterns of ACL tears were observed and
      designated as type 1 (diffuse increase in signal on T2-weighted images and
      enlargement of the ligament, 48%); type 2 (horizontally oriented ACL, 21%); type
      3 (nonvisualization of the ACL, 18%); type 4 (discontinuity of the ACL, 11%); and
      type 5 (vertically oriented ACL, 2%). The positive predictive value (PPV) for
      type 2, 4, and 5 patterns was 100% for both field strengths: for type 3 PPV was
      just above 80% for both field strengths. The PPV value for type 1 was 90% for the
      high-tesla unit and 79% for the low-tesla, unit, which was not statistically
      significant. Combining the results of both field strengths, the overall
      sensitivity and specificity were 93% and 89%, respectively. Arthroscopic results
      were also used to determine the association between meniscal and ACL tears. Only
      13% of ACL tears were isolated, the rest being associated with meniscal tears.
      Forty-five percent of medial meniscal and 50% of lateral meniscal tears were
      associated with an ACL tear, and 94% of ACLs were torn when both menisci were
      torn.

PMID- 8738001
TI  - Digital subtraction arthrography in preoperative evaluation of painful total hip
      arthroplasty.
AB  - OBJECTIVE: The objective of this clinical study was to define the diagnostic
      value of plain radiography, digital subtraction arthrography and two-phase bone
      scintigraphy in patients with clinically loose or infected hip prostheses.
      DESIGN: Digital subtraction arthrograms, scintigrams and plain radiographs of 70
      consecutive patients who underwent revision hip arthroplasty were scored
      individually and in masked fashion for the presence or absence of features
      indicating loosening of femoral and/or acetabular components. The operative
      findings acted as the gold standard. RESULTS: Digital subtraction arthrography
      was best (P < 0.001) for predicting a loose acetabular component, while no
      significant additional predictive value was found for plain radiographs (P =
      0.24) and scintigraphy (P = 0.27). Digital subtraction arthrography was also the
      most important modality for predicting a loose femoral component (P = 0.001),
      while the plain radiograph was of significant (P = 0.04) additional value and
      scintigraphy was of no additional value (P = 0.13) on multivariate analysis.
      CONCLUSION: Digital subtraction arthrography gives the best results in the
      prediction of loosening of acetabular and femoral components. Plain radiographs
      give additional information on loosening of the femoral component, but
      scintigraphy offers no additional advantage.

PMID- 8738003
TI  - Inflammatory reaction in chondroblastoma.
AB  - OBJECTIVE: The objective of this study was to evaluate the inflammatory reaction
      accompanying chondroblastoma and to define the value of the finding in clinical
      practice. DESIGN: We reviewed the clinical, radiographic, and magnetic resonance
      (MR) findings in six patients with histologically proven chondroblastoma.
      RESULTS: In all cases, MR imaging showed marrow and soft tissue edema. In four of
      six cases, periosteal reaction related to intra-osseous edema was more clearly
      demonstrated on MR imaging than on radiographs. Follow-up MR studies after
      surgery were available in three patients and all showed disappearance of
      inflammatory responses such as marrow and soft tissue edema, and reactive
      synovitis. CONCLUSION: We propose that these inflammatory reactions of
      chondroblastomas are important signs for detecting residual tumor in recurrences
      after surgery, as well as for making a precise diagnosis. The MR changes may also
      be valuable in demonstrating eradication of the tumor.

PMID- 8738004
TI  - Hyperostotic and osteosclerotic changes of the tarsal navicular, associated with
      pustulosis palmaris and plantaris.

PMID- 8738005
TI  - Periosteal ganglion of the tibia.
AB  - Radiographic, computed tomographic and scintigraphic findings of a patient with
      separated, multilocular periosteal ganglion are reported. Multiple periosteal
      cystic masses with calcification in small parts of the cyst walls were
      demonstrated in the surface of the left tibia by plain radiograms and CT. The
      accumulations of technetium-99m hydroxymethylene diphosphonate and pentavalent
      technetium-99m dimercaptosuccinic acid were shown in the calcification in the
      periosteum and wall of the cyst. Needle puncture revealed that the masses were
      filled with jelly-like fluid. The masses were diagnosed as multiple ganglionic
      cysts at the periosteum of the left tibia.

PMID- 8738006
TI  - Hyperplastic callus formation in both femurs in osteogenesis imperfecta.
AB  - A 3-year-old boy with osteogenesis imperfecta had hyperplastic callus formation
      in the right femur, without preceding trauma or fracture. Radiologically, this
      bony mass in the femoral shaft mimicked osteosarcoma. Open biopsy showed that it
      was benign and suggested hyperplastic callus formation. Seven months after the
      biopsy, the hyperplastic callus had practically vanished. A similar process
      developed in the left femur 1 year later, also without fracture.

PMID- 8738007
TI  - Idiopathic tumoral calcinosis involving the cervical spine.
AB  - We report a case of a 12-year-old girl with idiopathic tumoral calcinosis of the
      neck. There are calcium deposits in the paraspinal soft tissue with bony
      involvement in the cervical spine. CT and MR images are presented along with
      clinical and pathological features. Bony involvement in this disease has not been
      recognized before.

PMID- 8738008
TI  - Epithelioid hemangioendothelioma of bone.
AB  - Neoplasms of bone can arise from any of the cellular elements that constitute
      osseous tissues. Although tumors of vascular origin are not uncommon, the vast
      majority are benign. A rare malignant vascular tumor--epithelioid
      hemangioendothelioma of bone--classifically affects young males and produces
      osteolytic lesions involving the cortex and cancellous bone of the lower
      extremities. We present a case with these findings, as well as such unusual
      findings as cervical spine instability and lesions affecting no fewer than 45
      different bones. We conclude that epithelioid hemangioendothelioma should be
      investigated by skeletal survey because (1) osteolytic lesions involving more
      that 50% of the cortex present a serious risk for pathologic fracture and (2) the
      natural history of multicentric epithelioid hemangioendothelioma is more indolent
      than its solitary counterparts.

PMID- 8738009
TI  - Synovial cysts of the hips in seronegative arthritis.
AB  - A 25-year-old woman with recurrent pronounced enlargement of the iliopsoas bursae
      is described; her hips were evaluated by ultrasonography and MRI. They appeared
      normal and communications to the iliopsoas bursae were demonstrated. During the
      preceding 8 years she had intermittent seronegative non-erosive arthritis of the
      knee and finger joints and her disease was classified as juvenile chronic
      arthritis.

PMID- 8738010
TI  - Alveolar soft part sarcoma.
AB  - We present a rare case of alveolar soft-tissue sarcoma, with extensive bone
      invasion. The differential diagnosis with bone metastasis and primary bone tumors
      is discussed.

PMID- 8738011
TI  - Gorham's disease of the spine.
AB  - Massive osteolysis is a rare condition and is very uncommon in the spine. The MRI
      appearance of Gorham's disease of the spine has not previously been reported. We
      present here a case of this condition with imaging details.

PMID- 8738012
TI  - Periosteal chondroma of the clavicle.
AB  - We report a case of periosteal chondroma of the clavicle. To our knowledge, this
      benign cartilaginous tumor has never been previously reported in this location.
      Clinical, radiographic and pathological investigations were necessary to
      establish the diagnosis. Marginal excision proved an effective treatment.

PMID- 8738013
TI  - Extraskeletal soft tissue masses of Langerhans' cell histiocytosis.
AB  - Typically, soft-tissue involvement with Langerhans' cell histiocytosis (LCH) is
      the result of extension from adjacent bone marrow. We present a patient who
      developed soft-tissue masses of LCH, which did not arise as a result of extension
      from bone marrow, but instead produced extrinsic cortical erosion, preserving the
      marrow signal on MRI.

PMID- 8738014
TI  - Sensitive flow-injection method with peroxyoxalate chemiluminescence detection
      combined with preparative high-performance liquid chromatography for
      determination of choline-containing phospholipids in human serum.
AB  - A sensitive and rapid flow-injection analysis (FIA) of total choline-containing
      phospholipids (PLs) and a selective FIA method for the class assay of choline
      containing PLs combined with preparative HPLC were described. The FIA method is
      based on peroxyoxalate chemiluminescence (PO-CL) detection of hydrogen peroxide
      enzymatically formed from choline-containing PL. The linear standard curves were
      obtained up to 1 nmol/20-microliters injection (r > 0.999) with the detection
      limits of 1.3-1.6 pmol at a signal-to-noise ratio of 2. The total amounts of
      choline-containing PLs in human serum were ranged from 1.63 to 3.19 mg/ml. The
      HPLC separation of choline-containing PLs was achieved with an aminopropyl
      modified silica gel column using a mixture of acetonitrile-methanol-10 mM
      ammonium phosphate buffer pH 5.8 as eluent. The eluate corresponding to each
      choline-containing PL was collected, evaporated, dissolved in 0.1% Triton X-100
      aqueous solution, and then injected into FIA system. The FIA method combined with
      preparative HPLC was applied to the assay of human serum.

PMID- 8738015
TI  - Quality control in the determination of cortisol in plasma/serum by using, on
      every sample, two different three-step separation methods including
      ultrafiltration, restricted-access high-performance liquid chromatography and
      reversed-phase high-performance liquid chromatography, and contrasting results to
      immunoassays.
AB  - Tests of HPLC columns with restricted access, polymer covered alumina, polymer,
      and different ODS phases showed that base-acid compatible ODS columns gave the
      best peak shapes of cortisol, internal standard, as well as of plasma/serum (P/S)
      matrix components. Further trials with cortisol in P/S showed that three
      separation steps were essential in order to obtain chromatographic data which
      were superior to immunoassay data. Also, sufficient confidence in results
      required determination of each sample with two newly developed separation
      methods: (a) pre-separation with a restricted access column, concentration of the
      desired cut with a 20 mm base-acid compatible ODS column, and analysis with a 250
      mm column filled with the same ODS; (b) pre-separation with an ultrafilter
      followed by the last two steps in (a). For detection UV was preferred over
      fluorescence. This twin multistep chromatography showed that immunoassays were
      very treacherous in that they produced a spectrum of results ranging from good to
      untenable without any warning whatever about functionality. The measurement of
      official controls, with reference values derived via gas chromatography-isotope
      dilution mass spectrometry, also demonstrated the superiority of the double HPLC
      method.

PMID- 8738016
TI  - Determination of acetylcholine by on-line microdialysis coupled with pre- and
      post-microbore column enzyme reactors with electrochemical detection.
AB  - A sensitive procedure consisting of a pre- and post-microbore column reactor
      sequence of a LC-electrochemical detection system coupled with on-line
      microdialysis system is described in the present study to measure endogenous
      acetylcholine concentration in freely moving rats. The pre-column packed, with
      immobilized choline oxidase and catalase, was used to remove choline, whereas the
      post-column, packed with immobilized acetylcholine oxidase and choline oxidase,
      was used to measure acetylcholine selectively. The detection limit of
      acetylcholine oxidase and choline oxidase, was used to measure acetylcholine
      selectively. The detection limit of acetylcholine was found to be 5
      fmol/microliter (50 fmol/10 microliters). The usefulness of the described
      methodology was evaluated by examining the change in the striatal acetylcholine
      concentration of freely moving rats after physostigmine (0.5 mg/kg, s.c.)
      administration.

PMID- 8738017
TI  - Determination of reduced and oxidized glutathione in erythrocytes by high
      performance liquid chromatography with ultraviolet absorbance detection.
AB  - A method is described for simultaneous quantitation of reduced (GSH) and oxidized
      (GSSG) glutathione in erythrocytes by HPLC. They were determined by standard
      addition method. Blood samples were collected in tubes containing 1,10
      phenanthroline. The separated erythrocytes were hemolyzed with water containing
      standard. After deproteinization, GSH and GSSG were converted to N-(2,4
      dinitrophenyl) derivatives and analyzed by HPLC with UV detection. The
      coefficients of variation of GSH and GSSG on replicate assays were 6% and 8%,
      respectively. The stabilities of GSH and GSSG and of the derivatives were also
      examined. The present method appears to be satisfactory for determination of
      these physiological concentrations in erythrocytes.

PMID- 8738018
TI  - New marker of bone resorption: hydroxyproline-containing peptide. High
      performance liquid chromatographic assay without hydrolysis as an alternative to
      hydroxyproline determination: a preliminary report.
AB  - A high-performance liquid chromatographic (HPLC) assay for a urinary
      hydroxyproline-containing peptide (hydroxy-proline peptide, HypP) is described.
      This peptide represents about 50% of urinary hydroxyproline-containing peptides.
      Its concentration and total 4-hydroxyproline (Hyp) concentration evaluated in 325
      urine samples have been shown to be closely correlated (r = 0.972; y = 0.499 x 
      1.5), which may indicate that the two markers provide the same information. The
      HypP assay, similar to Hyp assay, is carried out without hydrolysis of urine
      samples. After the blocking of primary amino acids by o-phthaldialdehyde (OPA)
      and derivatization of secondary amino acids by 9-fluorenylmethyl chloroformate
      (FMOC-CI), the FMOC derivatives of HypP and 3,4-dehydroproline (internal
      standard) were separated on a strong anion-exchange column and detected
      fluorimetrically. HypP concentration was calculated by measurement of peak-area
      ratios of HypP and the hydroxyproline standard. The HypP/creatinine (mmol/mol)
      ratio in fasting urine samples from healthy adults was found to be 8.2 (S.D. =
      1.6, n = 33) in 27-44-year-old premenopausal women and 6.9 (S.D. = 1.7, n = 21)
      in 28-49-year-old men.

PMID- 8738019
TI  - Method for the isolation of biologically active monomeric immunoglobulin A from a
      plasma fraction.
AB  - A purification method for immunoglobulin A (IgA) yielding monomeric IgA with a
      purity of over 97% has been developed. This procedure uses ethanol-precipitated
      plasma (Cohn fraction III precipitate) as the starting material and includes
      heparin-Sepharose adsorption, dextran sulfate and ammonium sulfate precipitation,
      hydroxyapatite chromatography, batch adsorption by an anion-exchange matrix and
      gel permeation. Additional protein G Sepharose treatment leads to an IgA
      preparation of greater than 99% purity. The isolated IgA presented with an IgA
      subclass distribution, equivalent to IgA in unfractionated plasma, and was
      biologically active, as was shown by its ability to down-modulate Haemophilus
      influenzae-b-induced IL-6 secretion of human monocytes.

PMID- 8738020
TI  - Simultaneous detection of nucleotides, nucleosides and oxidative metabolites in
      myocardial biopsies.
AB  - A new simple, simultaneous matrix HPLC methodology was developed to facilitate
      better peak separability and resolution for the determination of levels of
      myocardial tissue nucleotides, nucleosides and oxidative metabolites. The
      components of interests were ATP, AMP, ADP, IMP, hypoxanthine, xanthine,
      adenosine, inosine, NAD, and NADH, which are used to establish myocardial
      cellular energy status and effectiveness of cardioprotection. Their detection was
      achieved using a 4-microns spherical bead, 300 x 3.9 mm I.D. Nova-Pak C18 column
      in a 12% methanol mobile phase solvent selection, ion-pairing reagents 1.47 mM
      TBAP (tetrabutylammonium phosphate) and 73.5 mM KH2PO4, at a pH of 4.0. The
      extraction method was modified for rapid determination to ensure diminished acid
      labile NADH effects. Comparisons of peak retention (k), resolution (Rs) of
      solvents of varying concentrations and pH adjustment facilitated this method.
      This isocratic single run determination allows for simple, simultaneous rapid
      quantification and identification of alterations in high-energy phosphates,
      nucleoside degradation products and NAD/NADH levels associated with myocardial
      ischemia, with excellent reliability.

PMID- 8738021
TI  - Liquid chromatographic determination of carotenoids in human serum using an
      engineered C30 and a C18 stationary phase.
AB  - A C30 stationary phase was specifically engineered for carotenoid separations,
      and carotenoid measurements using this column are compared with those obtained
      using a somewhat more conventional C18 column. Both methods were used to
      contribute measurements for the certification of carotenoids in Standard
      Reference Material 968b, Fat-Soluble Vitamins and Cholesterol in Human Serum.
      Analytes were extracted from the serum into hexane. Measurements on the C18
      column were made using a gradient of acetonitrile, methanol, and ethyl acetate,
      which is described in detail elsewhere. Measurements on the C30 column were made
      using a gradient of water, methanol, and methyl tert.-butyl ether.

PMID- 8738022
TI  - Monitoring for occupational exposure to 4,4'-methylenebis(2-chloroaniline) by gas
      chromatographic-mass spectrometric analysis of haemoglobin adducts, blood, plasma
      and urine.
AB  - The feasibility of using plasma, blood and haemoglobin adducts for monitoring
      occupational exposure to the suspected human carcinogen 4,4'-methylenebis(2
      chloroaniline) (MOCA) was investigated. A method utilising capillary gas
      chromatography-negative-ion chemical-ionisation mass spectrometry (GC-MS) for the
      determination of pentafluoropropionyl (PFP) derivatives of MOCA, released by
      alkaline hydrolysis from protein adducts and conjugates, was both sensitive and
      selective. When selected ion monitoring was used, sub-femtomole amounts of PFP
      MOCA could be measured. The detection limit for haemoglobin adducts of MOCA was
      below 10 fmol/g Hb, well below the levels found for occupationally exposed
      individuals. Capillary GC with electron-capture detection also had the required
      sensitivity for the determination of MOCA in blood samples, however, the presence
      of interfering compounds in some samples limited its use. The levels of MOCA in
      the blood and urine of five individuals who were exposed to MOCA during the
      manufacture of polyurethane elastomers were determined by the GC-MS method. The
      MOCA concentrations for the various blood fractions and urine were within the
      following ranges: haemoglobin adducts, 0.73-43.3 pmol MOCA/g Hb; plasma alkaline
      hydrolysate, 0.05-22.0 nmol/l; whole blood, 0.13-17.4 nmol/l; urine, 4.5-2390
      nmol/l. Because the products of MOCA in the blood reflect metabolic activation of
      MOCA and integrate exposure over a period of weeks, the use of blood samples for
      monitoring exposure to MOCA offers advantages over the currently used urinary
      MOCA measurements.

PMID- 8738024
TI  - Determination of phenylbutazone and oxyphenbutazone in plasma and urine samples
      of horses by high-performance liquid chromatography and gas chromatography-mass
      spectrometry.
AB  - A method is described for the qualitative and quantitative determination of
      phenylbutazone and oxyphenbutazone in horse urine and plasma samples viewing
      antidoping control. A horse was administered intravenously with 3 g of
      phenylbutazone. For the qualitative determination, a screening by HPLC was
      performed after acidic extraction of the urine samples and the confirmation
      process was realized by GC-MS. Using the proposed method it was possible to
      detect phenylbutazone and oxyphenbutazone in urine for up to 48 and 120 h,
      respectively. For the quantitation of these drugs the plasma was deproteinized
      with acetonitrile and 20 microliters were injected directly into the HPLC system
      equipped with a UV detector and LiChrospher RP-18 column. The mobile phase used
      was 0.01 M acetic acid in methanol (45:55, v/v). The limit of detection was 0.5
      microgram/ml for phenylbutazone and oxyphenbutazone and the limit of quantitation
      was 1.0 microgram/ml for both drugs. Using the proposed method it was possible to
      quantify phenylbutazone up to 30 h and oxyphenbutazone up to 39 h after
      administration.

PMID- 8738023
TI  - Gas chromatographic-mass spectrometric method to characterise the transfer of
      dietary odorous compounds into plasma and milk.
AB  - The flavours contained in a mammalian mother's milk can exert a marked influence
      on her offspring's proximate suckling behaviour and later preferences. The aim of
      this study was to establish a reliable analytical procedure to characterise the
      mammary transfer of selected volatile constituents of maternal food from non
      pregnant and recently parturient ewes. Six known volatile compounds, most
      representative of cumin aroma (alpha-pinene, gamma-terpinene, cuminaldehyde, p
      cymene, limonene and cineole), were traced in the blood and milk of ewes fed with
      cumin seeds, using liquid-liquid extraction combined with gas chromatography
      specific ion monitoring mass spectrometry. Among the six cumin odour markers,
      only one, p-cymene, was transferred in quantifiable amounts into the venous
      plasma. The other cumin markers could only be detected as traces corresponding to
      amounts lower that the limit of quantification. In milk, four of the cumin
      markers could be detected, and two of these were quantified.

PMID- 8738026
TI  - Direct plasma liquid chromatographic-tandem mass spectrometric analysis of
      granisetron and its 7-hydroxy metabolite utilizing internal surface reversed
      phase guard columns and automated column switching devices.
AB  - An alternative on-line automated sample enrichment technique useful for the
      direct determination of various drugs and their metabolites in plasma is
      described for rapid development of highly sensitive and selective liquid
      chromatographic methods using mass spectrometric detection. The method involves
      direct injection of plasma onto an internal surface reversed-phase (ISRP) guard
      column, washing the proteins from the column to waste with aqueous acetonitrile,
      and backflushing the analytes onto a reversed-phase octyl silica column using
      switching valves. The analytes were detected using a tandem mass spectrometer
      operated in selected reaction monitoring (SRM) mode using atmospheric pressure
      chemical ionization (APCI). Use of two ISRP guard columns in parallel
      configuration allowed alternate injections of plasma samples on these columns for
      sample enrichment and shortened the column equilibration and LC-MS-MS analysis
      times, thereby increasing the sample throughput. The total run time, including
      both sample enrichment and chromatography, was about 6 min. Using this technique,
      an analytical method was developed for the quantitation of granisetron and its
      active 7-hydroxy metabolite in dog plasma. Granisetron is a selective 5-HT3
      receptor antagonist used in the prevention and treatment of cytostatic induced
      nausea and vomiting. Recovery of the analytes was quantitative and the method
      displayed excellent linearity over the concentration ranges tested. Results from
      a three day validation study for both compounds demonstrated excellent precision
      (1.3-8.7%) and accuracy (93-105%) across the calibration range of 0.1 to 50 ng/ml
      using an 80 microliters plasma sample. The automated method described here was
      simple, reliable and economical. This on-line approach using ISRP columns and
      column switching with LC-MS-MS is applicable for the quantification of other
      pharmaceuticals in pharmacokinetic studies in animals and humans which require
      high sensitivity.

PMID- 8738025
TI  - Gas chromatographic-mass spectrometric assay for N-2-chloroethylaziridine, a
      volatile cytotoxic metabolite of cyclophosphamide, in rat plasma.
AB  - A sensitive and specific method for the quantitative analysis of N-2
      chloroethylaziridine (CEA), a volatile cytotoxic metabolite of cyclophosphamide,
      has been developed using gas chromatography-mass spectrometry and stable isotope
      dilution techniques. The high volatility problem of CEA during isolation
      procedure was overcome by the combined use of a deuterium-labeled analog as the
      internal standard and a Snyder column-concentrator assembly. The assay was found
      to be linear from 16.7 to 2667 ng/ml in rat plasma with a routine detection limit
      of 5 ng/ml. The within-run precision at 33, 333 and 1333 ng/ml (n = 6) was found
      to be 4.8, 4.9, and 6.1%, respectively. The between-run precision was 6.4% (n =
      6). The dichloromethane extraction recoveries at 33, 333, and 1333 ng/ml were
      found to be 101, 98, and 91%, respectively (all at n = 6). However, the overall
      recovery through extraction and evaporation was only 18.3, 15.2, and 27.7% at 33,
      333, and 1333 ng/ml levels, respectively. The analytical method was used to
      evaluate the generation of CEA from its precursors in sodium phosphate buffer, in
      cell culture media, and the degradation of CEA in these media. In pH 7.4, 0.067 M
      sodium phosphate buffer at 37 degrees C, both phosphoramide mustard (PM) and
      nornitrogen mustard (NNM) were degraded in an apparent first-order fashion with
      half-lives of 24.8 and 14.5 min, respectively. The generated CEA was rather
      stable in this buffer and degraded with a half-life of 20 h. It was found that
      32% PM and 91% NNM were converted to CEA in pH 7.4, 0.067 M sodium phosphate
      buffer at 37 degrees C, respectively, and 41% PM was transformed into CEA in RPMI
      1640 tissue culture media containing 10% FBS at 37 degrees C. The generated CEA
      was very stable in the culture media with a degradation half-life of 265 h.

PMID- 8738027
TI  - Stereoselective high-performance liquid chromatographic analysis of ketoprofen
      and its acyl glucuronides in chronic renal insufficiency.
AB  - A rapid, sensitive method was developed for the quantification of the R- and S
      enantiomers of ketoprofen and their acyl glucuronide conjugates in the plasma and
      dialysate of hemodialysis-dependent anephric patients. Unconjugated R- and S
      ketoprofen plasma concentrations were determined directly by liquid
      chromatography using a S,S-Whelk-O1 chiral stationary phase. R- and S-Ketoprofen
      glucuronide for use as standard were resolved using a C18 reversed-phase HPLC
      column with a mobile phase containing the ion-pair reagent tetrabutylammonium
      hydrogen sulfate. Plasma glucuronides, however, could not be directly quantified
      due to matrix interference. Therefore, the glucuronides were isolated using
      reversed-phase HPLC and quantified after alkaline hydrolysis using the S,S-Whelk
      O1 chiral stationary phase column.

PMID- 8738028
TI  - High-performance liquid chromatographic determination of phenylephrine in human
      serum with coulometric detection.
AB  - A high-performance liquid chromatographic method for the determination of
      phenylephrine (PE) in human serum using coulometric detection is described. PE
      and internal standard, orciprenaline, were extracted from serum by solid-phase
      extraction and separation achieved on a coupled column system consisting of two
      C18 cartridge columns (250 x 4.6 mm I.D. coupled to a shorter 50 x 4.6 mm I.D.
      column) using a mobile phase of methanol-50 mM phosphate buffer (pH 3.2; 10:90)
      at 36 degrees C. Dual electrode coulometric detection was used in the "oxidative
      screen" mode. Calibration curves were linear over the range 0.3-4 ng/ml with a
      limit of quantification (LOQ) of 0.35 ng/ml. The method has a greater degree of
      sensitivity, precision and accuracy compared to previously published methods for
      PE and is suitable for use in pharmacokinetic and bioequivalence studies in
      humans.

PMID- 8738029
TI  - Quantification of the beta-adrenoceptor ligand S-1'-[18F]fluorocarazolol in
      plasma of humans, rats and sheep.
AB  - Myocardial and pulmonary beta-adrenoceptors can be imaged with 2-(S)-(-)-(9H
      carbazol-4-yl-oxy)-3-[1-(fluoromethyl)ethyl]amino-2- propanol (S-1'
      [18F]fluorocarazolol, I). Quantification of unmodified fluorocarazolol in plasma
      is necessary for analysis of PET images in terms of receptor densities. We have
      determined I and its radioactive metabolites in rat, sheep and human plasma,
      using (1) solid-phase extraction (C18) followed by reversed-phase HPLC and (2)
      direct injection of untreated plasma samples on an internal-surface reversed
      phase (ISRP) column. The two methods were in good agreement. Unmodified I
      decreased from over 99% initially to less than 5%, 5-10% and 20% at 60 min post
      injection in rats, sheep and human volunteers, respectively. Protein binding in
      sheep and human plasma was determined by ultrafiltration. The fraction of total
      plasma radioactivity bound to protein and the fraction representing unmodified
      radioligand were linearly correlated, suggesting that fluorocarazolol was more
      than 70% protein-bound, whereas its metabolites showed negligible protein
      binding. Direct injection of plasma on an ISRP column seems a convenient method
      for quantification of lipophilic radioligands such as fluorocarazolol.

PMID- 8738030
TI  - Determination of alosetron in human plasma or serum by high-performance liquid
      chromatography with robotic sample preparation.
AB  - A method of analysis for the determination of alosetron in human plasma or serum
      has been developed. The method was fully automated using a laboratory robot in
      order to improve analytical precision, efficiency and safety. The assay involved
      solid-phase extraction with reversed-phase HPLC separation and fluorescence
      detection. A validation exercise over the concentration range of 0.1 to 20 ng/ml
      demonstrated the selectivity, linearity, sensitivity, accuracy, precision,
      extraction efficiency, ruggedness and stability of the method. The method has
      been applied in support of numerous human pharmacokinetic/biopharmaceutic studies
      over the last five years.

PMID- 8738031
TI  - Determination of a novel indolylpiperazine anti-migraine agent in rat, monkey,
      mouse and rabbit plasma by high-performance liquid chromatography with
      electrochemical detection.
AB  - A specific, accurate, precise and reproducible assay for the quantitation of a
      novel indolylpiperazine anti-migraine agent (I) in plasma from various animal
      species is described. The method involves addition of internal standard (I.S.)
      and 1.0 M sodium carbonate to the plasma sample, vortex-mixing and extraction
      with ethylene dichloride. The organic layer is then back-extracted in a buffer
      consisting of 0.1 M tetramethylammonium hydroxide (TMAH), pH 3.0 and 0.1 M
      (NH4)2HPO4, pH 3.0, in water. The aqueous layer is injected on to a Zorbax cyano
      analytical column with a mobile phase consisting of acetonitrile, methanol and
      water (15:5:80, v/v/v) with 0.01 M TMAH, pH 3.0 and 0.01 M (NH4)2HPO4, pH 3.0.
      The eluate is monitored by electrochemical detection at 0.9 V (guard cell), 0.5 V
      (detector 1) and 0.8 V (detector 2). The retention times of I and I.S. were 7 and
      10 min, respectively. In drug-free control plasma, there were no interfering
      peaks seen at the retention times of I or I.S. The standard curve was linear over
      the concentration range of 5-500 ng/ml in rat, monkey, mouse and rabbit plasma.
      The lower limit of quantitation in all four matrices was 5.0 ng/ml. Within- and
      between-assay variability of quality control samples was less than 9% relative
      standard deviation and the predicted concentration of the quality control samples
      deviated by less than 15% from the nominal concentration. The stability of I was
      established for up to 36 h in the autosampler tray, up to 10 months in plasma at 
      20 degrees C and up to 2 h in plasma at room temperature. The assay is validated
      for determination of I in plasma.

PMID- 8738032
TI  - High-performance liquid chromatographic assay of propofol in human and rat plasma
      and fourteen rat tissues using electrochemical detection.
AB  - This paper describes a sensitive HPLC-electrochemical detection analytical method
      for determining the concentration of the intravenous anesthetic, propofol, in
      human or rat plasma or serum and a variety of rat tissues. Internal standard and
      drug are extracted from serum or plasma and other tissues with pentane. 2,6-tert.
      Butylmethylphenol is used as internal standard. It includes a novel steam
      distillation procedure for separating the highly lipophilic propofol from skin
      and fat. The plasma/serum assay has a precision of 1-4% (C.V.) in the range 10
      ng/ml to 1 microgram/ml and permits the assay of assay of 5 ng/ml from 0.1 ml of
      plasma/serum. The tissue procedure allows the estimation of 50 ng/g in 0.1 g of
      tissue for most of the major organs with less than 2% (C.V.) precision. This
      assay was used to measure propofol concentrations in plasma/serum and tissue
      samples in support of a project to develop a physiological pharmacokinetic model
      for propofol in the rat.

PMID- 8738033
TI  - Determination of nalbuphine by high-performance liquid chromatography with
      ultraviolet detection: application to human and rabbit pharmacokinetic studies.
AB  - A rapid, sensitive, precise and accurate high-performance liquid chromatographic
      assay with ultraviolet detection was developed for the determination of
      nalbuphine in human, rabbit, pig and dog plasma. It is comprised of only a one
      step extraction procedure with hexane-isoamyl alcohol at pH 9.25 and reversed
      phase chromatography on a micro Porasil column. The recoveries of nalbuphine and
      ethylmorphine (internal standard) were greater than 86%. Calibration graphs were
      linear over the concentration range 0.75-150 ng/ml with a coefficient of
      variation, both within-day and between-day, of less than 10% at any level. The
      limit of quantitation was 0.75 ng/ml of plasma based on a signal-to-noise ratio
      of 3. Seven other clinically used analgesics were investigated to check for
      potential interferences and their analytical conditions. The specificity of this
      assay was checked with a metabolite of nalbuphine (noroxymorphine). Nalbuphine in
      plasma did not decompose significantly at -20 degrees C for six weeks.
      Pharmacokinetic application in three surgical patients and four rabbits revealed
      that nalbuphine followed a linear three-compartment model with two distribution
      phases. The two distribution and one elimination half-lives and the plasma
      clearance of nalbuphine were 0.9, 5.8 and 157 min and 370 ml/min in human, and
      3.5, 28 and 117 min and 21 166 ml/min in rabbits.

PMID- 8738034
TI  - Determination of the potent antiprotozoal compound atovaquone in plasma using
      liquid-liquid extraction followed by reversed-phase high-performance liquid
      chromatography with ultraviolet detection.
AB  - A specific and robust method is presented for the determination of atovaquone in
      plasma. Atovaquone is a potent antiprotozoal compound for use in
      immunocompromised patients who are intolerant of conventional therapies. The
      method involves a liquid-liquid extraction of the compound into hexane modified
      with 2% (v/v) isoamyl alcohol. The processed extracts are analysed by reversed
      phase high-performance liquid chromatography with ultraviolet detection at 254
      nm. The assay has a limit of quantification of 0.1 microgram/ml and is linear
      between 0.1 and 50 micrograms/ml. The method has been applied to many clinical
      studies and has been demonstrated to be precise and accurate with high sample
      throughput. Atovaquone is not significantly metabolised in humans.

PMID- 8738035
TI  - Determination of a HIV protease inhibitor (DMP 450) in animal and human plasma by
      solid-phase extraction and high-performance liquid chromatography.
AB  - Extraction of DMP 450 from plasma was performed with C2 solid-phase extraction
      columns, using 0.1 M ammonium acetate in 90% methanol to elute DMP 450. The
      extraction recovery over the range of 10 to 10 000 ng/ml averaged 81.0, 96.2,
      77.4, 95.2 and 68.0% from rat, dog, monkey, chimpanzee (25-10 000 ng/ml) and
      human plasma, respectively. HPLC analysis was carried out with a C18 column and a
      mobile phase of acetonitrile, methanol and 30 mM potassium phosphate (pH 3), the
      composition dependent on the type of plasma being analyzed, and monitored at a
      wavelength of 229 nm. Intra-day and inter-day coefficients of variation were less
      than 9.9 and 12.9%, respectively. Absolute differences were less than 11.5%.

PMID- 8738036
TI  - Sensitive high-performance liquid chromatographic fluorescence assay for the
      quantitation of topotecan (SKF 104864-A) and its lactone ring-opened product
      (hydroxy acid) in human plasma and urine.
AB  - A sensitive reversed-phase high-performance liquid chromatographic fluorescence
      method is described for the simultaneous determination of topotecan (I) and the
      hydrolysed lactone ring-opened product hydroxy acid (II) in plasma and for the
      determination of I in urine. To 250 microliters of plasma, a 750-microliters
      volume of cold methanol was added to stabilize the pH-dependent conversion of I
      into II. In plasma, the lower limit of quantitation (LLQ) for both compounds was
      0.10 ng/ml. The between-day variation for I at the LLQ was 7.1% and for II was
      5.5%. Prior to injection, urine samples were acidified with orthophosphoric acid
      and diluted with phosphate-buffered saline (PBS). In urine, the calibration curve
      for I was linear in the range of 10 to 250 ng/ml and the LLQ was 10 ng/ml. The
      assay was developed to enable pharmacological analysis of I, in on-going phase I
      and II studies, in patients with solid tumors.

PMID- 8738037
TI  - Solid-phase extraction and high-performance liquid chromatographic determination
      of tamoxifen and its major metabolites in plasma.
AB  - Tamoxifen (TAM) is a triphenylethylene anti-oestrogen, commonly used in the
      treatment of breast cancer. Patients receiving tamoxifen therapy may experience
      both de novo and acquired resistance. As one of the mechanisms for this may be
      extensive peripheral bio-transformation of tamoxifen, there has been considerable
      interest in the pharmacokinetics and metabolism of tamoxifen. A reversed-phase
      high-performance liquid chromatography separation has been developed to determine
      the levels of tamoxifen and its major metabolites in human plasma. The method is
      highly sensitive (2 ng/ml) and selective for tamoxifen, cis-tamoxifen (CIS), 4
      hydroxytamoxifen (4-OH) and desmethyltamoxifen (DMT). A micro Bondapak C18 10
      microns column (30 cm x 3.9 mm I.D.) was used, with a mobile phase of methanol-1%
      triethylamine at pH 8 (89:11, v/v). Sample preparation was carried out using a C2
      (500 mg sorbent, 3 ml reservoirs) solid phase extraction method, and extraction
      efficiencies were approximately 60% for TAM and its metabolites. Accuracy and
      precision, as determined by spiking plasma samples with a mixture of tamoxifen
      and its metabolites, ranged from 85-110% (+/- 5-10%) at 1 microgram/ml, 101-118%
      (+/- 8-20%) at 0.1 microgram/ml and 111-168% (+/- 43-63%) at 0.01 microgram/ml.
      Results from 59 patients show mean values of 54 ng/ml for 4-OH; 190 ng/ml for
      DMT; 93 ng/ml for TAM and 30 ng/ml for CIS (detected in three patients only).
      This methodology can be applied routinely to the determination of TAM and its
      metabolites in plasma from patients undergoing therapy.

PMID- 8738038
TI  - Extraction and measurement of pamidronate from bone samples using automated pre
      column derivatization, high-performance liquid chromatography and fluorescence
      detection.
AB  - A method for the determination of 3-amino-1-hydroxylpropylidene-1, 1
      bisphosphonic acid (pamidronate) in bone samples is described. This method
      combines and modifies parts of previous procedures. Pamidronate is extracted from
      finely ground bone with dilute hydrochloric acid. Amine-containing contaminants
      are removed by co-precipitation of pamidronate with calcium. Excess calcium is
      removed with EDTA and an ion-exchange resin. Pamidronate is automatically
      derivatized at the primary amine and quantified by high-performance liquid
      chromatography with fluorescence detection. The method assay was linear in the
      concentration range 7.5-600 ng/mg bone (20-100 pmol/mg). The imprecision for
      repeat analyses were 16.5 and 7.8%, at pamidronate levels of 7.5 and 600 ng/mg
      bone, respectively. The method has been used to analyze bone samples from
      pharmacokinetic animal studies involving both acute and chronic dosages.

PMID- 8738039
TI  - Application of capillary electrophoresis to the simultaneous screening and
      quantitation of benzodiazepines.
AB  - Capillary electrophoresis (CE) is an attractive approach for the analysis of
      drugs in body fluids. We made a simultaneous analysis of nitrazepam, diazepam,
      estazolam, bromazepam, triazolam and flurazepam using CE with on-column detection
      at 200 nm. We obtained the best electropherograms under a condition of 5 mM
      phosphate-borate (pH 8.5) containing 50 mM SDS and 15% methanol. We examined the
      effect of the sample solvent matrix on the electropherograms obtained, indicating
      that increasing the methanol content in the sample solvent or the injection
      volume above a certain threshold limit decreased the resolution. We then focused
      on application of the CE to the analysis of the drugs in spiked serum, being
      appropriate for an analysis within 25 min. Linearity, the detection limit,
      accuracy and reproducibility were established using this method. The calibration
      curve was linear up to 1 mg/l of serum concentration. The lower limit of
      detection was 5 pg per injection and 0.025 mg/l of the serum concentration for
      all the compounds except for flurazepam, for which they were 40 pg/injection and
      0.2 mg/l. The detection limits obtained allowed toxicological and pharmacological
      determinations for nitrazepam, diazepam, estazolam and bromazepam, but not for
      triazolam and flurazepam. Only toxic blood levels for the latter two
      benzodiazepines could be quantified by this method. We concluded that the CE
      could at least be applicable to simultaneous screening for toxic levels of
      benzodiazepines. We suggest that this technique may offer criminal toxicologists
      a rapid, simple and adaptable approach for the estimation of many other drugs in
      body fluids.

PMID- 8738040
TI  - High-performance liquid chromatography-thermospray mass spectrometry of 5,6
      dihydroxyeicosatrienoate-1,5-lactone from tissue homogenates.
AB  - We have developed a method for the analysis of 5,6-dihydroxyeicosatrienoate-1,5
      lactone (5,6-DiHETriE-delta-lactone) in tissue homogenates, supplemented with
      NADPH and arachidonic acid [20:4(n-6)] as a substrate. During the incubation and
      the extraction, most of the 5,6-epoxyeicosatrienoic acid (5,6-EpETriE) was
      converted to 5,6-dihydroxyeicosatrienoic acid (5,6-DiHETriE), and most of the 5,6
      DiHETriE was converted to 5,6-DiHETriE-delta-lactone. Consequently, the chief
      degradation product of 5,6-EpETriE and 5,6-DiHETriE in the incubation mixture was
      5,6-DiHETriE-delta-lactone. 5,6-DiHETriE-delta-lactone, corresponding to [20:4(n
      6)], was shown to be characterized by a high intensity of quasimolecular ions
      (MH+ and MNH4+), using ion analysis obtained by reversed-phase HPLC-thermospray
      MS. On selected-ion monitoring (SIM) chromatograms of 5,6-DiHETriE-delta-lactone
      and with deuterium-labeled 15(S)-hydroxyeicosatetraenoic acid as the internal
      standard, the regression equation of the peak-area ratio and the amount of 5,6
      DiHETriE-delta-lactone was y = 12.2x + 0.7 (r = 0.9996). 5,6-Epoxygenase activity
      was represented as the sum of the amount of 5,6-DiHETriE-delta-lactone, 5,6
      EpETriE and 5,6-DiHETriE per mg protein, after 30 min in an incubation mixture.
      The activity from rat brain homogenate decreased considerably with growth of the
      rat.

PMID- 8738041
TI  - Facile analysis of ribonucleotides in D,L-alpha-difluoromethylornithine-treated
      mouse lymphoid cells by high-performance anion-exchange column chromatography.
AB  - Using high-performance liquid chromatography with the strong anion-exchange resin
      column CDR-10 for analysis of ribonucleotides, the effects of D,L-alpha
      difluoromethylornithine (DFMO) on ribonucleotides of mouse leukemic lymphoid
      cells SC-1 have been studied. More than 16 nucleoside mono-, di and
      triphosphates, and unknown peaks were clearly separated and measured without
      increase in baseline rise using the gradient systems of phosphate buffer. The ATP
      level in DFMO-treated SC-1 cells was reduced, but was reversed by exogenous
      putrescine. These facts may suggest that polyamine depletion by DFMO during a
      short time (6 h) caused mitochondrial damage in mammalian cells.

PMID- 8738042
TI  - Determination of the terfenadine metabolite azacyclonol in human serum using gas
      chromatography-mass spectrometry.
AB  - In this work, a method for the determination of azacyclonol, a primary metabolite
      of terfenadine, in human serum is described. Sample preparation is carried out by
      liquid-liquid extraction under basic conditions. For an efficient clean up, the
      analytes are back-extracted into diluted hydrochloric acid and, after
      alkalinization, are once again extracted into the organic phase. No
      derivatisation step is performed. The samples are measured by gas chromatography
      mass spectrometry with good selectivity. The limit of detection is 2 ng/ml. The
      coefficients of variation are 12.6% at 10 ng/ml and 6.44% at 200 ng/ml in the day
      to-day control measurements.

PMID- 8738043
TI  - Simultaneous determination of isosorbide dinitrate and its mononitrate
      metabolites in human plasma by capillary gas chromatography with electron-capture
      detection.
AB  - A method for the simultaneous determination of isosorbide dinitrate (ISDN) and
      its mononitrate metabolites (2- and 5-ISMN) in human plasma by capillary gas
      chromatography with electron-capture detection was developed. Two internal
      standards were used: isomannide dinitrate (IMDN) for the determination of ISDN
      and isomannide mononitrate (IMMN) for the determinations of 2- and 5-ISMN. After
      addition of the internal standards, the compounds were isolated from plasma by
      solid-liquid extraction. They were determined by gas chromatography using an
      electron-capture detector. The reproducibility and accuracy of the method were
      found suitable in the range of concentrations 2.5-83 ng/ml for ISDN, 2.6-208
      ng/ml for 2-ISMN and 2.3-1010 ng/ml for 5-ISMN. The limit of quantitation (LOQ)
      was about 2.5 ng/ml for each compound. The method was applied to clinical
      samples.

PMID- 8738044
TI  - Automated gas chromatographic assay for amlodipine in plasma and gingival
      crevicular fluid.
AB  - This paper describes an automated capillary gas chromatographic method for the
      determination of amlodipine in plasma, and in sub-microlitre volumes of gingival
      crevicular fluid (GCF), in order to assess if amlodipine is present in GCF under
      conditions of gingival overgrowth, as has been shown for nifedipine, another
      dihydropyridine drug. Liquid-liquid extraction followed by derivatisation was
      employed to isolate amlodipine and render it suitable for gas chromatography.
      Amlodipine was analysed in plasma and GCF of four patients undergoing amlodipine
      therapy for cardiovascular disorders, three of whom had significant gingival
      overgrowth. Amlodipine was detected in the plasma of all patients and in massive
      concentrations in the GCF of those patients with overgrowth, 23- to 290-fold
      greater than in their plasma. Like nifedipine, amlodipine sequestration into GCF
      appears to be linked with gingival overgrowth.

PMID- 8738045
TI  - High-performance liquid chromatography of flufenamic acid in rat plasma.
AB  - A simple high-performance liquid chromatographic (HPLC) method for the
      determination of flufenamic acid in rat plasma is described. After liquid-liquid
      extraction, the drug is separated by HPLC on a 5-microns octadecylsilica column
      (Nucleosil C18) with ultraviolet detection at 280 nm. Linear calibration graphs
      for flufenamic acid were constructed from 0.5 to 15 micrograms/ml. The method has
      been applied to a pharmacokinetic study in animals.

PMID- 8738046
TI  - High-performance liquid chromatographic assay of mepivacaine enantiomers in human
      plasma in the nanogram per milliliter range.
AB  - A method enabling quantification of R-(-)- and S-(+)-mepivacaine in human plasma
      in the low nanogram per milliliter range is described. The procedure involves
      extraction from plasma with diethyl ether, centrifugation, back-extraction into
      an acidified aqueous solution, washing with a mixture of pentane and
      isoamylalcohol, alkalinisation, followed by extraction with a mixture of n
      pentane and isoamylalcohol. After evaporation of the organic phase, the residue
      is redissolved in the mobile phase used for the HPLC analysis, which consists of
      a 6.8:93.2 (v/v) isopropanol-sodium hydrogenphosphate buffer solution with the pH
      adjusted to 6.8 using phosphoric acid. The HPLC method has been described
      previously. Separation of the enantiomers is achieved with an alpha 1-AGP column
      and the UV detection wavelength is 210 nm. The minimal detectable concentration
      is ca. 3 ng/ml and the lower limit of quantification is 5 ng/ml for each
      enantiomer. For both enantiomers r is > 0.9995 over the plasma enantiomeric
      concentration range of 10.5-1053 ng/ml.

PMID- 8738047
TI  - Determination of ketamine and norketamine enantiomers in plasma by solid-phase
      extraction and high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic method is described for determination
      of sub-anaesthetic concentrations of the enantiomers of ketamine and its
      metabolite norketamine in plasma. The samples are purified by reversed-phase
      solid-phase extraction. The enantiomers are separated on a Chiral AGP column with
      a mobile phase containing 16% methanol and a 10 mM phosphate buffer at pH 7.0,
      and measured by UV-detection at a wavelength of 220 nm. Linear calibration curves
      with correlation coefficients better than 0.995 have been obtained in the range
      10-320 ng/ml. Minimum detectable concentrations were about 2 ng/ml.

PMID- 8738048
TI  - Liquid chromatographic assay in plasma of one of the members of a new series of
      anticonvulsants: D,L-3-hydroxy-3-ethyl-3-phenylpropionamide.
AB  - A method for the simultaneous determination of HEPP (D,L-3-hydroxy-3-ethyl-3
      phenylpropionamide), a member of a new homologous series of phenylamide
      derivative anticonvulsants, with six other antiepileptic drugs (ethosuximide,
      primidone, phenobarbital, phenytoin, carbamazepine and clonazepam) in plasma by
      high-performance liquid chromatography is described. These drugs are extracted
      from plasma by adding an equal volume of acetonitrile. An aliquot of the extract
      is then injected on a reversed-phase column with a acetonitrile-methanol
      phosphate buffer mobile phase. The total time required for the whole analytical
      process, including the plasma pretreatment and chromatography, is approximately
      30 min. The assay method is simple, rapid and reproducible, and therefore
      considered suitable for routine use in clinical investigations monitoring HEPP
      simultaneously with common antiepileptic drugs.

PMID- 8738049
TI  - Determination of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine in human
      plasma by solid-phase extraction and column-switching high-performance liquid
      chromatography with ultraviolet detection.
AB  - A column-switching high-performance liquid chromatography method with ultraviolet
      detection at 210 nm has been developed for the determination of N-(trans-4
      isopropylcyclohexylcarbonyl)-D-phenylalanine (AY4166, I) in human plasma. Plasma
      samples were prepared by solid-phase extraction with Sep-Pak Light tC18, followed
      by HPLC. The calibration graph for I was linear in the range 0.1-20
      micrograms/ml. The limit of quantitation of I, in plasma, was 0.05 microgram/ml.
      The recovery of spiked I (0.5 microgram/ml) to drug-free plasma was over 92% and
      the relative standard deviation of spiked I (0.5 microgram/ml) compared to drug
      free plasma was 4.3% (n = 8).

PMID- 8738050
TI  - The pituitary gland in nocturnal enuresis: MR findings.
AB  - Nocturnal enuresis is considered a benign condition partially explained by a
      defect circadian rhythm of vasopressin. An organic cause may be responsible for
      an abnormal pituitary function, when enuresis persists into adulthood. In the
      present study the pituitary gland and surroundings of 8 adults suffering from
      primary monosymptomatic nocturnal enuresis were studied by magnetic resonance
      imaging. The pituitary gland appeared normal in all, except from a Rathke's cleft
      cyst observed in one patient. This cleft cyst was not considered to be clinically
      important. It was concluded, that severe nocturnal enuresis persisting into
      adulthood is not likely to be combined with detectable pathology on magnetic
      resonance imaging of the pituitary gland.

PMID- 8738051
TI  - Residual urine in 75-year-old men and women. A normative population study.
AB  - The prevalence of residual urine in elderly people in the community is poorly
      documented. The aim of the present study was to assess the prevalence and range
      of residual urine in elderly people in the community. As part of a major
      epidemiologic study (The Glostrup Population Study), 140 75-year-old men and
      women were included in this study (92 men, 48 women). All were selected at random
      from the Central Person Register by age and residence. All had a single
      sonographic measurement of residual urine with a prevoid volume of 150 ml or
      more. More than 10 ml of residual urine was found in 91 of the 92 men (median 90
      ml; range 10-1502 ml), and in 44 of the 48 women (median 45 ml; range 0-180 ml).
      Our figures correspond to those previously reported in selected patient
      populations. It must be emphasized, however, that our findings are merely
      descriptive, as the clinical significance of a single residual urine
      determination is questionable.

PMID- 8738052
TI  - Randomised study of Casodex 50 MG monotherapy vs orchidectomy in the treatment of
      metastatic prostate cancer. The Scandinavian Casodex Cooperative Group.
AB  - The effect of Casodex (ICI 176,334), a new, once-daily, selective antiandrogen,
      given as 50 mg monotherapy, was compared with orchidectomy in a randomised,
      multicentre, open study in 376 patients with metastatic prostate cancer. At 3
      months, PSA was reduced by 86% in the Casodex group and by 96% in the
      orchidectomy group. Treatment failed in 51 patients in the orchidectomy group and
      66 showed a subjective response. Treatment failed in 86 patients treated with
      Casodex and 40 patients showed a subjective response. Patients treated with
      Casodex maintained their sexual interest better than those in the orchidectomy
      group. Median survival was significantly longer in the orchidectomy group.
      Casodex was well-tolerated. The most likely reason for the differences between
      the groups regarding time to treatment failure and survival is that the dose of
      Casodex was too small. Further studies with higher doses of Casodex are in
      progress.

PMID- 8738053
TI  - Sexual function before and after transurethral microwave thermotherapy for benign
      prostatic hyperplasia.
AB  - The effect of transurethral microwave thermotherapy (TUMT) for benign prostatic
      hyperplasia (BPH) on the ability of achieving erection and ejaculation was
      studied in one hundred and twenty patients. The patients underwent a single TUMT
      session for one hour without complementary treatment during the follow-up period
      of one year. A self-administered questionnaire on sexual functions was used. Our
      results showed that, despite individual reductions, there was an overall
      improvement in the ability to achieve erection. It was concluded that TUMT did
      not have any major adverse effects on sexual functions. However, it was not
      possible to predict that TUMT will improve sexual functions for the individual
      patient. Improvement of symptoms and a better quality of life may influence the
      results.

PMID- 8738054
TI  - Symptomatic outcome of transurethral prostatectomy, alpha-blockade and placebo in
      the treatment of benign prostatic hyperplasia. Evaluation of treatment with the
      Danish Prostatic Symptom Score (DAN-PSS-1) system. The ALFECH Study Group.
AB  - To assess the symptomatic outcome following transurethral prostatectomy (TURP),
      alpha-blockade and placebo treatment in uncomplicated benign prostatic
      hyperplasia (BPH), 260 patients were evaluated with the recently formulated
      Danish Prostatic Symptom Score (DAN-PSS-1) system: 205 were randomized to either
      the selective alpha-blocker alfuzosin or placebo and 55 underwent TURP. Following
      TURP, the DAN-PSS-1 score was reduced by 80% after 6-10 weeks (visit 2) and by
      100% after 12-16 weeks (visit 3). In the alfuzosin group the corresponding
      reductions were 40% and 65% (p < 0.02 vs. placebo). In the placebo group the
      reduction was 25% at visit 2, with no further fall demonstrated thereafter.
      During alfuzosin treatment the bother score (impact of symptoms on quality of
      life) fell more than the symptom score. During placebo treatment there was no
      reduction in symptom score. We conclude that the DAN-PSS-1 questionnaire
      sensitively identifies clinically important responses to treatment of BPH.

PMID- 8738055
TI  - Long-term outcome of patients treated for hydrocele with the sclerosant agent
      sodium tetradecyl sulphate.
AB  - The long-term outcome of 106 patients treated for hydrocele with the sclerosing
      agent sodium tetradecyl sulphate was examined. In a questionnaire distributed at
      a mean time of 40 months after therapy 83/86 (96%) of the eligible patients
      responded and 95% of them were satisfied with the treatment and its long term
      results. The treatment associated pain was evaluated on a visual analogue scale
      (0-10) the mean pain score was found to be 1.8 and the mean duration of the pain
      2.4 days. When all hydroceles were considered the overall success rate was 88%.
      Side-effects were minor apart from two patients (1.9%) with diabetes mellitus who
      had an intense inflammatory reaction necessitating orchidectomy after
      sclerotherapy.

PMID- 8738056
TI  - Renal anaemia treatment with recombinant human erythropoietin increases cardiac
      output in patients with ischaemic heart disease.
AB  - An increase in blood pressure is common during treatment of renal anaemia with
      recombinant human erythropoietin (rhEPO). Concomitant findings of a decrease in
      cardiac output indicate that an increase in the peripheral flow resistance
      underlies the increase in blood pressure. The aim of this study was to elucidate
      the haemodynamic changes during rhEPO treatment in patients with ischaemic heart
      disease (IHD). Haemodynamic variables were assessed by impedance cardiography in
      18 consecutive patients with renal anaemia before and after rhEPO treatment. IHD
      was found in eleven of these patients. The remaining seven served as controls.
      Before rhEPO treatment, the cardiac index was decreased in the group of patients
      with IHD, compared with controls and healthy subjects. Due to an increase in
      stroke index, the cardiac index increased during rhEPO treatment and reached
      values equal to those in the control group. The blood pressure increased and the
      increase in mean arterial pressure was correlated to the increase in cardiac
      index. Apparently the patients with IHD were unable to compensate for anaemia by
      increasing their cardiac index. Anaemia treatment increased cardiac index, which
      in turn caused an increase in blood pressure in these patients.

PMID- 8738057
TI  - Glomerular filtration rate in primary Sjogren's syndrome with renal disease.
AB  - Renal disease in Primary Sjogren's syndrome (SS) is often overlooked, because of
      a paucity of symptoms. Distal renal tubular acidosis (dRTA) and
      tubulointerstitial nephritis (TIN) might be present. Only a few cases of SS with
      decreased glomerular filtration rate (GFR) have been reported. We have studied
      GFR in 27 female SS-patients, mean age 62 years (37-78). GFR was measured as the
      single injection 51Cr-EDTA plasma clearance. Eighteen women had normal GFR (group
      1), and nine (33%) had values below the lower normal limit (group 2). In group 2,
      dRTA was present in 8/9 urolithiasis in 6/9, previous upper urinary tract
      infection (UTI) in 2/9 and TIN in 5/6 patients who were kidney biopsied. Among
      patients with dRTA 8/18 (44%) had decreased GFR. We conclude that decreased GFR
      is not unusual in SS-patients with dRTA, and decreased GFR is mostly associated
      with TIN. Urolithiasis and UTI may contribute to decreased GFR in some
      individuals.

PMID- 8738058
TI  - Effects of androgen therapy on prostatic markers in hemodialyzed patients.
AB  - We have prospectively studied the evolution of serum levels of the prostatic
      specific antigen and prostatic acid phosphatase in 14 male hemodialyzed patients,
      receiving a cycle of nandrolone decanoate (200 mg intramuscularly, once a week,
      for six months) as treatment for anemia. Androgen administration did not produce
      significant increases in serum concentrations of both tumor markers (basal: 0.9
      +/- 0.5 and 0.7 +/- 0.3 ng/ml; at six months: 1.3 +/- 1.1 and 0.8 +/- 0.7 ng/ml
      respectively). Only one patient had a value of prostatic-specific antigen over
      the normal range: 4.2 ng/mol at the sixth month period, with a rapid decrease
      after the withdrawal of androgens. All the remaining values of both markers were
      within the normal range. In another six patients undergoing a prolonged treatment
      with androgens (between 9 to 24 months), the serum levels of prostatic-specific
      antigen and prostatic acid phosphatase were within the normal range in all of
      them. Nandrolone decanoate administration does not induce increases in prostate
      tumor markers when it is used as treatment for anemia in hemodialyzed patients.

PMID- 8738059
TI  - Thoracic ectopic kidney in an adult.
AB  - We are presenting an adult patient with a rare form of renal ectopy. Our patient
      had a thoracic kidney with complications. He presented with symptoms unrelated to
      the urinary system and his chest x-ray showed an intrathoracic mass presenting
      just above the diaphragm. An excretory urogram may be necessary for the diagnosis
      in such patients with similar chest x-ray findings.

PMID- 8738060
TI  - A non-urologic cause of nocturia and enuresis--obstructive sleep apnea syndrome
      (OSAS).
AB  - Three case reports describe nocturia and enuresis as complications of the
      obstructive sleep apnea syndrome (OSAS). It is important to recognize the causal
      relationship since these troublesome symptoms are easily treated by treating the
      sleep apnea.

PMID- 8738061
TI  - Contralateral adrenal metastasis in renal cell cancer.
AB  - A 60-year-old female patient presenting with anemia was found to have a left
      sided renal tumor and a contralateral adrenal mass of 2 cm in diameter. Imaging
      studies for metastases were negative. Nephrectomy along with contralateral
      adrenalectomy was performed and histology disclosed renal cell carcinoma stage
      pT3a pNO G2 with solitary contralateral adrenal metastasis. In a survey of the
      literature, 24 previous cases of renal cancer with solitary contralateral adrenal
      metastasis were identified. The most probable biological pathway to explain this
      peculiar metastatic pattern is transpulmonal passage of circulating cancer cells
      and seeding in the adrenal gland on the basis of a particular susceptibility of
      adrenal tissue to circulating renal cancer cells. The case illustrates that
      surgery of solitary metastases from renal cell carcinoma may be beneficial to the
      patient. The case further highlights the caution that is required diagnostically
      in the interpretation of incidentally found adrenal masses when other
      malignancies are present.

PMID- 8738062
TI  - Percutaneous endopyelotomy for ureteropelvic junction obstruction in a horseshoe
      kidney.
AB  - Two patients with ureteropelvic junction (UPJ) obstruction in a horseshoe kidney
      underwent percutaneous endopyelotomy. No major complications were observed and
      good results were obtained for two years. Percutaneous endopyelotomy is an
      effective and safe treatment for UPJ obstruction in a horseshoe kidney.

PMID- 8738063
TI  - Distal urethral duplication--a case report and literature review.
AB  - Patient with partial duplication of the distal penile urethra ending blindly in
      the periurethral tissue, without an external meatus is reported. Relevant
      literature and the classification of urethral duplication is discussed.

PMID- 8738064
TI  - Severe bleeding following transrectal Tru-cut prostatic biopsy.

PMID- 8738065
TI  - Malakoplakia of the prostate gland--report of two cases and review of the
      literature.
AB  - Malokoplakia of the prostate is extremely rare. We report two cases of prostatic
      malokoplakia in one 60-year-old and one 64-year-old Libyan man, who both were
      presented with enlarged prostate containing firm to hard nodules. These cases may
      be misdiagnosed as carcinoma clinically, but the histology points out the correct
      diagnosis with the presence of Michaelis-Gutmann bodies in the proliferating
      histiocytes.

PMID- 8738066
TI  - Phytohemagglutinin-dependent T-cell proliferation is not impaired by morphine.
AB  - Opioids have been reported in the literature to have immunosuppressive
      properties. Thus, we investigated the influence of morphine, morphine-3
      glucuronide and morphine-6-glucuronide in vitro on phytohemagglutinin-stimulated
      proliferation of peripheral mononuclear cells from healthy humans. Furthermore,
      the effects of a 1-week treatment with morphine in a range of 30-240 mg/day on
      proliferation of lymphocytes from patients with chronic pain syndromes were
      evaluated. In addition, human peripheral mononuclear cell membranes were tested
      for specific opioid radioligand binding. The results show that i) morphine and
      its main metabolites do not influence mitogen-induced T-cell proliferation, ii)
      treatment of patients with sustained release morphine for 1 week did not impair
      the lymphocyte proliferative response, and iii) no specific binding of mu-, delta
      and kappa-radioligands could be demonstrated to membranes of peripheral
      lymphocytes obtained from healthy humans. These results do not indicate an
      impairment of phytohemagglutinin-induced T-cell proliferation during pain
      treatment with sustained release morphine.

PMID- 8738067
TI  - A paradox of thrombogenesis by streptokinase and its prevention by iloprost and
      camonagrel.
AB  - Here we report that streptokinase is responsible for forming thrombi both in
      vitro on blood-superfused endothelial cells of rabbit aorta and in vivo on blood
      superfused collagen strips in extracorporal circulation of anesthetized cats.
      This short-lasting paradoxical thrombogenic phase is followed by the expected
      long-lasting thrombolysis. The biphasic action of streptokinase occurred in vitro
      at concentrations of 100-2000 U/ml and in vivo at doses of 1000-3000 U/kg i.v.
      Both phases are mediated by endogenous plasmin as evidenced by deleting the
      streptokinase-induced thrombogenesis and thrombolysis following pretreatment with
      epsilon-aminocaproic acid or aprotinin. On the other hand, selective block of the
      paradoxical thrombogenesis was achieved after pretreatment with camonagrel, a
      thromboxane synthase inhibitor which raises plasma levels of endogenous
      prostacyclin, or with iloprost, a stable analog of prostacyclin. It is suggested
      that endogenous or exogenous prostacyclin inhibits activation of platelets by
      plasmin, and hence the thrombogenesis by streptokinase is abolished, while the
      beneficial thrombolytic action of streptokinase is augmented.

PMID- 8738068
TI  - Microscopic FT-IR/DSC system used to simultaneously investigate the conversion
      process of protein structure in porcine stratum corneum after pretreatment with
      skin penetration enhancers.
AB  - A newly developed microscopic Fourier transform infrared (FT-IR) spectrometry
      combined with differential scanning calorimetry (DSC) was used to investigate the
      thermal response and IR spectral changes of protein structure in porcine stratum
      corneum (SC) after pretreatment with the skin penetration enhancers propylene
      glycol (PG), azone/PG, oleic acid (OA)/PG, vitamin C, and vitamin C+ OA/PG. The
      amide I and II bands of protein were used as probe to determine the structural
      transformation of protein with temperature. A reheating process was also
      performed. Dual effects of enhancer and temperature on the protein conformational
      changes of porcine SC were studied. The results indicate that the new FT-IR/DSC
      system can continuously determine the thermoresponsive conversion process from
      alpha-helix to beta-sheet in keratin structure of porcine SC pretreated with
      different enhancers. The thermally induced keratin conversion in protein
      structure of porcine SC, independent of pretreatment with skin penetration
      enhancers, was irreversible. The process of conformational transition in protein
      was found to be partially from alpha-helix to random coil structure or partially
      from alpha-helix to beta-sheet structure during heating. The kinetics of this
      conversion between first-heating and second-heating processes were significantly
      different; the process of conversion for all first-heated porcine SC samples
      during second-heating process were slower than that of porcine SC samples during
      first-heating process. Moreover, it was also found that the skin penetration
      enhancers, when present during the heating process, were able to synergistically
      and promotively alter the keratin conversion in protein structure of porcine SC,
      with the PG, OA/PG and azone/PG enhancers being the most effective.

PMID- 8738069
TI  - Transcription of dopamine D1A receptor mRNAs in rat heart.
AB  - The existence of dopamine receptor subtypes in the heart has been suggested by
      pharmacological and biochemical techniques. So far, however, very little data is
      available as to the transcription of dopamine D1 subtype receptor genes in the
      heart. Therefore, in this study we employed reverse transcription-polymerase
      chain reaction (RT-PCR), which is a sensitive and highly specific method for
      identifying a low abundance mRNA in tissues, to determine if the D1A receptor
      gene was transcripted in the adult rat heart. Total RNA was isolated from the
      whole heart by the guanidium thiocyanate-CsCl method. Primers were based on the
      sequence of rat D1A cDNA cloned from the brain and corresponded to the third
      cytoplasmic loop of the receptor. A predicted size product (247bp) was evident
      from heart RNA. PCR performed in the absence of reverse transcriptase did not
      result in an amplification of the predicted product, indicating that these
      products were from cDNA and not from genomic DNA. The results demonstrate the
      existence of D1A receptor mRNA in the rat heart and that the D1A receptor in the
      heart are possibly identical to that from the brain. Since in this study the
      whole heart RNA was used, we cannot ascertain whether the mRNA comes from cardiac
      myocyte per se or from intermuscular coronary arterioles or from both.

PMID- 8738070
TI  - Effects of clofibrate on flow cytometric populations in rat liver.
AB  - A flow cytometric study was performed on the liver of normal and clofibrate
      treated rats. The flow cytometric patterns of these fractions showed three
      distinct populations (R1, R2 and R3). The R3 region was remarkably increased in
      the clofibrate-treated nuclear fraction, and was applied to sucrose linear
      density gradient centrifugation. Mt1, Mt2, Mt3 and Mt4 fractions were isolated
      and reacted with rhodamine-123. An essential enzyme for beta-oxidation, delta 3,
      delta 2-enoyl-CoA isomerase, was mainly expressed in Mt1 of the control-nuclear
      fraction, but not in Mt1, Mt2 and Mt4 in the clofibrate-treated nuclear fraction.
      These results suggest that clofibrate affects the flow cytometrical population of
      the mitochondria and changes the expression level of beta-oxidation enzyme(s) of
      the mitochondria in rat liver.

PMID- 8738071
TI  - Effects of S-9977-2 on histamine levels in rats.
AB  - S-9977-2 is a new molecule with promnesic and antiamnesic properties. In this
      study, we investigated the effects of i.p. administration of S-9977-2 on
      histamine (HA) levels in several regions of the rat brain, and also in peripheral
      areas, using high performance liquid chromatography (HPLC) with fluorometric
      detection. S-9977-2 (0.025 mg/kg) induced an increase in the content of HA in the
      anterior hypothalamic region, with a significant effect 30 min after injection
      (1.77 +/- 0.36 nmol/g vs. 2.43 +/- 0.40 nmol/g; p < 0.01). It did not
      significantly modify HA levels in the posterior hypothalamic region, hippocampus,
      fronto-parietal cortex, blood, spleen, or adrenal glands. A clear tendency to
      increase HA content was observed in the hippocampus (0.16 +/- 0.03 nmol/g vs.
      0.39 +/- 0.31 nmol/g, ns) and fronto-parietal cortex (0.55 +/- 0.45 nmol/g vs.
      0.70 +/- 0.28 nmol/g; ns). S-9977-2 at doses of 0.005 and 0.125 mg/kg i.p. did
      not produce any significant change in HA levels in any of the samples tested 30
      min after administration. The present results demonstrate that S-9977-2 increases
      HA levels in the anterior hypothalamus, which is the brain region with the
      highest content in histaminergic fibers. This fact suggests that the neuronal HA
      system might be involved directly or indirectly in the pharmacological actions of
      S-9977-2.

PMID- 8738072
TI  - Effects of perindopril treatment on plasma and urine of kallikrein activity and
      the stable metabolite of prostaglandin E2 in patients with essential
      hypertension.
AB  - Eleven male patients with essential hypertension were included in the study. They
      followed an unrestricted diet and received a single oral daily dose of 4 mg
      perindopril (ACE inhibitor) for 6 weeks. Plasma renin activity increased
      significantly and plasma aldosterone decreased significantly after perindopril
      treatment, suggesting that an effective blockade of angiotensin II formation was
      accomplished. Both systolic and diastolic blood pressure decreased. Urinary
      bicycloprostaglandin E2 (an inactive metabolite of prostaglandin E2) increased
      significantly, while plasma and urinary kallikrein activity decreased
      significantly after perindopril treatment. The results obtained demonstrated
      significant changes in prostaglandin E2 and kallikrein activity during ACE
      inhibition. The contributive role of these humoral factors in the hypotensive
      effect of perindopril are discussed.

PMID- 8738073
TI  - Respiratory and analgesic effects of meperidine and tramadol in patients
      undergoing orthopedic surgery.
AB  - The respiratory and analgesic effects of i.v. meperidine, tramadol and their
      correlation with plasma concentrations of meperidine, tramadol and O
      demethyltramadol were determined. Forty-eight patients after total hip or knee
      replacement were randomly distributed into 3 groups (n = 16 each). At the time of
      analgesia request, they received in a double-blind manner, i.v. single doses of
      100 mg meperidine, 100 mg tramadol, or saline. Thirty minutes after treatment,
      patients who requested additional analgesia were rescued with 75 mg diclofenac
      and morphine as required. Patients were evaluated at the time of analgesia
      request and at set intervals during 4 h. Meperidine induced sedation (p < 0.05),
      respiratory depression (tidal volume, p < 0.047; respiratory rate, p < 0.004; %
      O2 Sat, p < 0.036), and hypercapnia (PaCO2, p < 0.002). Incidence of nausea and
      vomiting was higher with tramadol (p < 0.02). For the first 30 min, meperidine
      produced lower pain intensity scores than tramadol or saline (p < 0.05). At this
      time, 14/16 patients on saline, 8/16 on meperidine and 11/16 on tramadol were
      rescued. Onset for meperidine analgesia was 10 min and > 30 min for tramadol.
      Both opioids produced similar degree of analgesia in patients who were not
      rescued. A negative correlation (r = -0.99) between analgesia and tramadol
      concentrations and a poor positive correlation (r = +0.54) with O
      demethyltramadol (a metabolite of tramadol) was observed. Pain intensity
      differences correlated negatively with meperidine plasma concentrations during
      the first 30 min (r = -0.97) and positively thereafter (r = +0.92). In the
      present study, meperidine and tramadol produced comparable analgesia, with a
      different time course profile, but meperidine induced sedation and respiratory
      depression while tramadol did not.

PMID- 8738074
TI  - Animal behavioral models for testing antianxiety agents.

PMID- 8738075
TI  - Andrology--development and future. Critical remarks after 45 years of medical
      practice.
AB  - The development of andrology from its beginning to the present time is discussed
      from a historical point of view. Since andrology is a clinical discipline, only
      well-trained physicians are allowed to investigate and treat patients. The term
      'andrology', which was first introduced in the USA more than 100 years ago, was
      independently reborn in Germany and thereafter used in other European countries.
      Since then, an increasing number of physicians all over the world have applied
      the term 'andrology' for their professional work. Many local societies and groups
      of andrologists were established. In 1969, Andrologia was founded as the first
      international journal of andrology in Germany. In the meantime, further
      andrological journals have been established. Concerning the future development of
      andrology, the following should be considered: (i) the organizational structure
      of andrology must include the basic training of physicians working in this field;
      (ii) the necessity of andrology as a medical specialty with regard to modern
      technologies of assisted reproduction etc., must be emphasized; (iii)
      internationally accepted recommendations for the training of andrologists with
      special reference to both clinical andrology and laboratory techniques should be
      established; (iv) andrology should be established as a separate specialty.

PMID- 8738076
TI  - Conception rates and assisted reproduction in subfertility due to unilateral
      cryptorchidism.
AB  - During 774 spontaneous cycles and 87 cycles of assisted reproduction, the
      conception rates were evaluated in 48 infertile couples in whom unilateral
      cryptorchidism was the causal factor. In spite of adjuvant therapy of the male
      partner, the spontaneous conception rate was very low (1% per cycle). Intra
      uterine insemination (IUI) and conventional in vitro fertilization (IVF) resulted
      in similar success rates of 6.1 and 8.7% per cycle/attempt respectively. After
      intra-cyto-plasmic sperm injection (ICSI), 46.7% pregnancies were obtained per
      attempt, and sperm requirements for the latter treatment to be successful were
      lower than for IUI. It is concluded that subfertility in men with unilateral
      cryptorchidism is severe, conventional IVF has little advantage, but ICSI is
      highly successful.

PMID- 8738077
TI  - The content and distribution of glycosaminoglycans in the ejaculates of normal
      and vasectomized men.
AB  - The glycosaminoglycans (GAGs) of sperm and seminal plasma of normal men and
      seminal plasma of vasectomized individuals have been identified and quantified by
      two dimensional (2D) electrophoresis. The sperm contains predominantly CSC and HS
      as well as significant amounts of DS which achieves a high level in the sperm of
      the youngest man, while HA and LSC are either undetectable or present in small
      quantities. In normal seminal plasma, characteristically, DS is essentially
      lacking whereas CSC is the major GAG and HA and LSC account for relatively high
      percentages. Interestingly, in the ejaculates of vasectomized men the DS content
      is relatively prominent and the HA concentration varies widely. The oversulfated
      chondroitin sulfates CSD/CSE were detected in 7 of the 37 specimens. Their
      presence in a normal human body fluid is reported for the first time and the
      previous observation of the youthful DS/CSC switch is expanded to this study.

PMID- 8738078
TI  - Extrapelvic cavernous nerve stimulation in erectile dysfunction. Human study.
AB  - An extrapelvic subpubic approach was used in dogs to stimulate the cavernous
      nerve (CN) with a resulting increase in the intracavernous pressure and full
      erection. This approach was used for the treatment of erectile dysfunction (ED)
      in 15 men with a mean age of 42.6 years (range from 32 to 55 years). Routine
      erectile function tests showed normal readings for endocrine assay, Doppler
      examination of the penile arteries, penobrachial pressure index and
      cavernosometry. Nocturnal penile tumescence was absent. The CN was exposed
      through a parapenile incision. The suspensory ligament was divided and the CN
      searched for in the area bounded by symphysis pubis, penile crura and urethra. A
      bipolar platinum electrode was implanted around CN and connected to a
      subcutaneous receiver. Implantation was performed bilaterally in eight subjects
      and unilaterally in seven. Two weeks after the operation, the CN was stimulated.
      CN stimulation at 10 Hz frequency led to penile tumescence but no rigidity;
      intracavernous pressure increased (P < 0.01). Upon increase of stimulation
      frequency, the penile tumescence as well as rigidity and pressure increased until
      full erection was achieved at 60 Hz. The latency and stimulation phase decreased
      with increase of stimulation frequency. Unilateral nerve stimulation induced
      erection as well. In conclusion, CN stimulation induced full erection in ED. The
      technique is extrapelvic and safe.

PMID- 8738079
TI  - Increased levels of interferon-gamma in seminal plasma of infertile men.
AB  - The role of the cell-mediated immunity in male infertility is still far from
      clear. Interferon-gamma (INF-gamma), a secretory product of activated T cells and
      natural killer cells, has been hypothesized to have a toxic effect on sperm
      function. The presence of INF-gamma was investigated in seminal plasma of fertile
      and infertile subjects, using a specific enzyme-linked immunosorbent assay, in
      order to study its role in male infertility. Forty-one subjects were studied; 20
      had proven fertility and normal semen quality (fertile group) and 21 showed male
      infertility for at least 2 years and poor semen quality (infertile group). INF
      gamma was present in significantly higher levels in the seminal plasma of
      infertile subjects (6.36 +/- 0.72 fmol ml-1) compared to fertile subjects (3.68
      +/- 0.30 fmol ml-1). Moreover, a significant negative correlation between INF
      gamma levels and sperm count, motility and morphology was detected, whereas no
      correlation between INF-gamma levels and leukocyte count was found. These
      findings (i) confirm INF-gamma to be present in seminal plasma; (ii) show
      increased INF-gamma secretion in the infertile group; (iii) demonstrate negative
      correlations of INF-gamma with the main spermiogram parameters and (iv) no
      correlation with leukocyte count. INF-gamma may therefore play an important role
      in male infertility.

PMID- 8738080
TI  - Control of gonadotropin secretion in prepubertal male rats by excitatory amino
      acids.
AB  - The role of N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the control of
      FSH and LH secretion was analysed in prepubertal male rats. In the first
      experiment 4, 8, 12, 16, 20 and 30-day-old males were decapitated 15 min after
      vehicle, NMDA or kainic acid (KA) administration. In the second experiment, 23
      day-old males were sham-orchidectomized or orchidectomized. Orchidectomized males
      were or were not implanted with silastic capsules containing testosterone and
      were sacrificed on day 30 after injection with vehicle, NMDA (15 mg kg-1), LHRH
      (100 ng rat-1), NMDA plus LHRH, or MK801, a non-competitive NMDA antagonist, (1
      mg kg-1). In the third experiment, 30-day-old intact males pretreated with Nw
      nitro-L-arginine methyl ester (NAME) or NG-methyl-L-arginine (MA), blockers of
      nitric oxide (NO) synthase, were sacrificed after NMDA or KA administration. In
      the fourth experiment, the effects of NMDA, KA, LHRH and NAME were analysed in
      monolayer cultures of dispersed adenohypophyseal cells. We found that: (i) NMDA
      and KA stimulated LH and FSH secretion in intact males; (ii) the NMDA effect on
      LH secretion remained after orchidectomy; (iii) FSH and LH responses to LHRH were
      not affected by simultaneous NMDA administration; (iv) antagonization of NMDA
      receptors with MK801 reduced the LH secretion in intact and orchidectomized males
      and blunted the FSH response to orchidectomy; (v) the stimulatory effect of NMDA
      or KA on LH secretion was not affected by pretreatment with blockers of NO
      synthase; (vi) the in vitro LH secretion remained unchanged after administration
      of NMDA, KA or NAME. We conclude that NMDA and non-NMDA receptors play a
      physiological role in the control of the basal and post-orchidectomy secretion of
      gonadotropins, and that this effects is independent of changes in NO generation
      and does not include changes in pituitary responsiveness to LHRH.

PMID- 8738081
TI  - Influence of media and thermal shock on sperm capacitation.
AB  - To elucidate the influence of medium and thermal shock in inducing sperm
      capacitation, eight ejaculates were processed as follows. Each ejaculate was
      divided into three aliquots. To two of the aliquots, an equal volume of saline
      was added, while TEST-yolk was added to the remaining aliquot. All three samples
      were cooled slowly to 5 degrees C and incubated for 18-20 h. After aspirating the
      supernatant, 6 ml of Tyrode solution containing 0.06 g% egg yolk, warmed to 37
      degrees C was added without disturbing the sperm pellet to the aliquot containing
      TEST-yolk and to one of the aliquots mixed with saline. To the remaining saline
      processed sperm pellet, 6 ml TEST-yolk (37 degrees C) was added. All samples were
      washed twice (400 x g for 5 min) and processed for the sperm penetration assay
      (SPA). Samples, either pre-incubated in TEST-yolk (mean +/- SEM; 65.9 +/- 11.7%)
      or warmed (thermal shock) with TEST-yolk (62.6 +/-12.1%) yielded significantly (P
      < 0.05) higher SPA outcome than the samples processed and warmed with saline
      (17.8 +/- 12.0%). The penetration indices were not statistically different from
      each other. It therefore appears that the medium influences the sperm
      capacitation process to a greater extent and may augment the influence of thermal
      shock.

PMID- 8738082
TI  - Evaluation of sperm cryoprotective media in respect to fertilizing capacity
      tested in vitro.
AB  - Nine different cryoprotectant buffers were tested to measure their protective
      ability towards main sperm seminological parameters. These were: maintained sperm
      motility, progressive motility and sperm viability. Out of the nine tested
      buffers, medium E (TES-Tris without glycerol) and H (glycerol only) showed
      significantly lower (P < 0.001) values than the rest of the studied buffers in
      respect to all tested seminological features. The other media did not differ
      significantly in their cryoprotective abilities to sperm. Richardson's medium (A)
      preserved sperm viability significantly better (P < 0.001) than the other tested
      buffers, reaching 63.1% of viable spermatozoa in proportion to the fresh sperm
      sample before freezing. Three cryoprotectants, A (with egg yolk, no TEST buffer
      system), D (neither egg yolk nor TEST buffer system), F (TEST-egg yolk buffer
      system) were further studied for their ability to preserve sperm function in
      sperm-cervical mucus penetration (Penetrak) and sperm penetration assay (SPA). In
      our hands, neither supplementation of the buffer with egg yolk nor TEST-egg yolk
      buffer system promoted sperm capacity in functional tests. A,D,F buffers did not
      significantly differ among each other in applied functional assays, however, they
      all diminished (P < 0.001) sperm penetration ratios when compared with fresh
      sperm samples. Therefore enhancement of sperm capacity to fertilize after
      equilibration with TEST-egg yolk buffer system should be contested.

PMID- 8738083
TI  - How should we estimate carotid stenosis using magnetic resonance angiography?
AB  - Our purpose was to assess the reproducibility of and differences between the most
      commonly used methods for assessing carotid artery stenosis using magnetic
      resonance angiography (MRA). We studied 55 patients who underwent axial three
      dimensional time-of-flight MRA (1.5 T). Quantitative caliper measurements were
      performed from maximum intensity projection (MIP) and multiple planar
      reconstruction (MPR) images, according to the criteria of the North American
      Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery
      Trial (ECST). The measurements were compared to each other and to visual
      interpretation, using conventional angiography as the reference. The measured
      percentage stenoses were higher on MRA than on digital subtraction angiography
      (DSA) using both NASCET (mean difference 1.9-3.0%) and ECST (6.3-6.7%) criteria.
      The kappa coefficients for the agreement between DSA and MRA were higher using
      the NASCET (0.61-0.76) than the ECST criteria (0.52-0.65). No statistically
      significant differences were found between measurements from MIP and MPR images.
      The ECST measurement criteria gave significantly higher percentage stenoses than
      the NASCET criteria (P < 0.001), this difference being more prominent on MRA
      (mean difference in diameter stenosis percentage 14.3-16.4%) than on DSA (7.6
      11.2%) and most important with mild stenoses. The difference between visual
      interpretation and quantitative measurements on MRA was significant (P = 0.01
      0.001). There were no statistically significant interobserver differences in the
      MRA film readings, either in visually estimated degrees of stenosis or stenosis
      measurements. Thus, the different criteria of the two multicentre trials led to
      significantly different results, especially in the assessment of mild stenosis,
      and these differences are more important with MRA than with DSA. Differences
      between the imaging modalities or the reconstruction programs seem less
      important.

PMID- 8738084
TI  - Intradiploic epidermoid cysts.
AB  - We studied 37 intradiploic epidermoid cysts, reviewing typical and atypical
      radiological features and the differential diagnosis. The most common clinical
      feature was a long standing lump in the scalp, occurring in 25 patients (67.7%).
      Plain films were the most cost-effective radiological technique in diagnosis. The
      typical finding was a well-defined lytic lesion with sclerotic border, seen in 29
      cases (78%). Atypical lesions were those larger than 5 cm and/or with an ill
      defined edge, being observed in 8 cases (22%). CT and MRI were the best methods
      for assessing atypical ones. In all cases with typical radiological findings a
      preoperative diagnosis of intradiploic epidermoid cyst was suggested.

PMID- 8738085
TI  - A controlled study of reliability and validity of MRI findings in neuro-Behcet's
      disease.
AB  - Our aim was to test the reliability of interpreting MRI studies in neuro-Behcet's
      disease (NBD) and to determine the sensitivity and specificity of different MRI
      findings. We prospectively studied 50 patients: 24 had chronic NBD, 12 multiple
      sclerosis, 5 vasculitis other than Behcet's disease (BD) and 9 patients had BD
      without neurological involvement. MRI studies were performed according to a
      standard protocol with a 0.2 T imager. Two neuroradiologists, blinded to the
      diagnosis, age and sex of the subjects, reviewed the films independently, twice.
      Separate assessments were made for a set of items: dural sinus pathology,
      widening of ventricles and sulci, brain stem atrophy, lesions of the cerebral
      cortex, discrete lesions of deep white matter, basal ganglia, brain stem and
      cerebellum and the presence of smooth periventricular high-signal foci.
      Intraobserver agreement was substantial or better, and interobserver agreement
      moderate to substantial for most items. In these patients with chronic NBD we
      found low sensitivity on all assessed items. Dural sinus pathology or brain stem
      atrophy were highly specific, but parenchymal lesions in different sites had
      uniformly low specificity.

PMID- 8738086
TI  - Lesion discrimination in optic neuritis using high-resolution fat-suppressed fast
      spin-echo MRI.
AB  - Fast spin-echo (FSE) is a new sequence with acquisition times currently down to
      one-sixteenth of those obtained with conventional spin-echo sequences, which
      allows high-resolution (512 x 512 matrix) images to be acquired in an acceptable
      time. We compared the higher resolution of FSE with the medium resolution of a
      short inversion-time inversion-recovery (STIR) sequence in depicting the optic
      nerves of healthy controls and patients with optic neuritis. Optic nerve MRI
      examinations were performed in 18 patients with optic neuritis and 10 normal
      controls. Two sequences were obtained coronally: fat-suppressed FSE (FSE TR 3250
      ms/TEef 68 ms, echo-train length 16, 4 excitations, 24 cm rectangular field of
      view, 3 mm interleaved contiguous slices, in-plane resolution 0.5 x 0.5 mm) and
      STIR (TR 2000 ms/TE 50 ms/TI 175 ms, in-plane resolution 0.8 x 0.8 mm, slice
      thickness 5 mm). FSE demonstrated much more anatomical detail than STIR, e.g.
      distinction of optic nerve and sheath. Lesions were seen in 20 of 21 symptomatic
      nerves using FSE and in 18 of 21 using STIR. Nerve swelling or partial cross
      sectional lesions of the optic nerve were each seen only on FSE in 3 cases. Fat
      suppressed FSE imaging of the optic nerve improves anatomical definition and
      increases lesion detection in optic neuritis.

PMID- 8738087
TI  - Balo's concentric sclerosis: MRI.
AB  - We report a case of Balo's concentric sclerosis. In the past, the diagnosis was
      usually made post mortem. In this case, we found that CT demonstrated only low
      density lesions, but not their concentric pattern. However, MRI showed a striking
      feature, reminiscent of histopathology of Balo's concentric sclerosis, and played
      an important role in antemortem diagnosis of this rare demyelinating disease.

PMID- 8738088
TI  - Whipple's disease confined to the central nervous system.
AB  - We report a 49-year-old woman with a left parietal lesion, shown on CT and MRI as
      an isolated ring-enhancing mass. The diagnosis of cerebral Whipple's disease was
      made by brain biopsy; there were no gastrointestinal symptoms nor periodic-acid
      Schiff-positive inclusions in the jejunal mucosa. This case illustrates atypical
      Whipple's disease, confined exclusively to the central nervous system.

PMID- 8738089
TI  - Intrasellar meningioma: characteristic imaging findings.
AB  - Intrasellar meningioma is rare. We present a case in which both angiography and
      dynamic contrast-enhanced MRI suggests the diagnosis.

PMID- 8738090
TI  - Craniocervical bone pneumatisation.
AB  - We report a case of extensive craniocervical bone pneumatisation presenting after
      minor trauma. The patient had neurological signs and initial radiographs showed
      multiple lucencies in the skull base and the atlas vertebra. CT established the
      true nature of this rare condition.

PMID- 8738091
TI  - Primary vertebral and spinal epidural non-Hodgkin's lymphoma with spinal cord
      compression.
AB  - We examined eight patients with primary spinal epidural non-Hodgkin's lymphoma
      presenting with spinal cord compression and proven histologically after
      laminectomy (7 cases) or biopsy (1 case) by MRI. The most common findings were an
      isointense or low signal relative to the spinal cord on T1-weighted images (T1WI)
      and high signal on T2-weighted images (T2WI). Spinal cord compression, vertebral
      bone marrow and paravertebral extension were assessed. Contrast enhancement was
      intense in seven of the eight cases and homogeneous in all of them. T2WI
      (performed in 2 cases) may be useful to distinguish metastatic carcinomas and
      sarcomas. T1WI demonstrated the full extent of the epidural lesion, which was
      well-delineated in all cases. When the paravertebral extension is not well
      defined, a study with contrast medium should be performed.

PMID- 8738092
TI  - Compressive myelopathy in fluorosis: MRI.
AB  - We examined four patients with fluorosis, presenting with compressive myelopathy,
      by MRI, using spin-echo and fast low-angle shot sequences. Cord compression due
      to ossification of the posterior longitudinal ligament (PLL) and ligamentum
      flavum (LF) was demonstrated in one and ossification of only the LF in one.
      Marrow signal was observed in the PLL and LF in all the patients on all pulse
      sequences. In patients with compressive myelopathy secondary to ossification of
      PLL and/or LF, fluorosis should be considered as a possible cause, especially in
      endemic regions.

PMID- 8738093
TI  - Epidural lipomatosis: case report and literature review.
AB  - We report a case of symptomatic epidural lipomatosis in a 36-year-old man
      following a heart lung transplant and 3.5 years of steroid medication. A review
      of the pertinent literature emphasises the importance of including this diagnosis
      in the differential diagnosis of patients receiving steroid medication or
      markedly obese patients with back pain or symptoms suggesting spinal cord or
      cauda equina compression.

PMID- 8738094
TI  - Accidental intrathecal injection of ionic water-soluble contrast medium: report
      of a case, including treatment.
AB  - We report a patient who inadvertently received a small amount of meglumine
      diatrizoate intrathecally. The physiopathology and treatment of this kind of
      accident are discussed.

PMID- 8738095
TI  - Medulloblastoma in children: CT and MRI findings.
AB  - Our purpose was to determine whether medulloblastoma (MB) shows specific
      neuroradiological features which may be employed in differential diagnosis from
      other common posterior cranial fossa tumours in childhood. Preoperative MRI was
      performed on 20 children with MB, and preoperative CT in 17 of them. All
      underwent surgery and histopathological diagnosis. There was a constant
      relationship between high density on CT and low signal on T1-weighted images.
      Signal behaviour on T2-weighted images and the degree of contrast enhancement
      were more variable. Most tumours arose in the midline, from the cerebellar
      vermis, involving the fourth ventricle, but hemisphere and extra-axial neoplasms
      were also seen. The combination of high density on CT and low signal on T1
      weighted images is highly suggestive of MB and may assist preoperative
      differential diagnosis from other posterior cranial fossa tumours.

PMID- 8738096
TI  - Infratentorial brain maturation: a comparison of MRI at 0.5 and 1.5T.
AB  - Our purpose was to establish parameters for normal infratentorial brain
      maturation at 0.5 and 1.5 T and to evaluate the field strength criteria for the
      assessment of infratentorial brain maturation with MRI. We examined 27 children
      with normal psychomotor development (3 days to 24 months) with a 1.5 T system and
      22 (4 days to 29 months) with a 0.5 T system; standard T2-weighted spin-echo
      sequences (TR/TE 2500/90 ms at 1.5 T and TR/TE 2200/90 ms at 0.5 T) were
      obtained. The signal intensity of infratentorial anatomical structures compared
      to their surroundings was classified as high, isointense or low by three
      neuroradiologists. For anatomical structures with age-related contrast changes,
      the time of these changes was determined statistically for the 0.5 T and 1.5 T
      system independently. The delineation of the structures without age-related
      contrast changes at the two field strengths was compared using a chi 2 test. Age
      related contrast changed were found in the same anatomical structures ("marker
      sites") at 0.5 and 1.5 T. Generally, these changes were apparent in larger
      structures (pons, middle cerebellar peduncles, medulla, cerebellar folia, red
      nuclei, cerebral peduncles), with only slight field-strength-dependent
      differences in the time of the contrast changes. Contrast changes from high to
      isointense signal were observed slightly earlier at 0.5 T and changes from
      isointense to low signal slightly later at 0.5 T. The delineation of the smaller
      anatomical structures was significantly better at 1.5 T but these structures did
      not show age-related contrast changes. The differences in the assessment of
      infratentorial brain maturation between 0.5 and 1.5 T can be attributed to a
      lower signal-to-noise ratio at lower magnetic field strengths. These differences
      do not complicate temporal classification of the stage of infratentorial brain
      maturation using the same "marker sites" and the same temporal criteria at 0.5 or
      1.5 T. However, higher field strengths are preferable for the assessment of
      smaller structures with physiological signal differences; this may imply better
      detection of small lesions at higher field strengths.

PMID- 8738097
TI  - Hemimegalencephaly associated with somatic hemihypertrophy and a malformation of
      the feet: case report.
AB  - Hemimegalencephaly (HME) is a rare neuronal migration anomaly, rarely associated
      with hemihypertrophy or some other somatic malformation; it can coexist with
      intracranial arteriovenous shunts which cause cardiac failure. We report a rare
      case associated with hemihypertrophy of the face, trunk and limbs and
      malformation of the feet. The neuroradiological findings are underlined and the
      differential diagnoses discussed.

PMID- 8738098
TI  - MRI in acute poliomyelitis.
AB  - MRI can be used in the diagnosis of anterior horn infection and for assessing the
      extent of disease. There are no specific MRI signs to differentiate between the
      various possible pathogens. This is demonstrated in the present case of
      poliomyelitis, in which MRI of the spine played an important role in establishing
      the diagnosis.

PMID- 8738099
TI  - MRI of congenital rhabdoid tumor of the neck: case report.

PMID- 8738100
TI  - MRI of nasopharyngeal carcinoma metastatic to the cerebellopontine angle.
AB  - In patients with nasopharyngeal carcinoma, intracranial spread may occur via
      direct extension from the base of the skull or via perineural spread. Perineural
      spread usually affects branches of the trigeminal nerve. We describe two patients
      with recurrent nasopharyngeal carcinoma, who presented with a solitary mass in
      the cerebellopontine angle without associated bony destruction. MRI findings
      mimicked those of acoustic schwannoma. The imaging findings and possible pathways
      of spread are discussed.

PMID- 8738101
TI  - Ultrasonography, CT and MRI of retropharyngeal ganglioneuroma: a very rare
      neoplasm in adults.
AB  - Ganglioneuroma, a rare benign tumour, very occasionally presents in adult life.
      We report a case with the additional unusual feature of a retropharyngeal
      location.

PMID- 8738102
TI  - Retained gauze in the sinonasal cavities: plain film and CT findings.
AB  - We report a case of retained packing gauze in the right maxillary sinus following
      a Caldwell-Luc operation. Plain films showed total opacification of the right
      maxillary sinus. CT showed a mixed mesh-like soft tissue density and air in the
      centre of the lesion and a thick soft tissue band at the periphery of the right
      maxillary and ethmoid sinuses and nasal cavity.

PMID- 8738103
TI  - Percutaneous transluminal angioplasty of atherosclerotic basilar artery stenosis.
AB  - Symptomatic intracranial involvement of vertebral and basilar arteries by
      atherosclerosis is not accessible to surgical treatment. We report a case of
      major basilar artery stricture responsible for haemodynamic strokes treated
      successfully by percutaneous dilatation.

PMID- 8738104
TI  - Development of right transverse sinus dural arteriovenous malformation after
      embolisation of a similar lesion on the left.

PMID- 8738105
TI  - Acrylic vertebroplasty in symptomatic cervical vertebral haemangiomas: report of
      2 cases.
AB  - We report two cases of acrylic vertebroplasty in symptomatic cervical vertebral
      haemangiomas. In both cases significant improvement of symptoms was rapid. One
      patient was able to return to work.

PMID- 8738107
TI  - Central IGF-1 decreases systemic blood pressure and increases blood flow in
      selective vascular beds.
AB  - IGF-1 and its receptors have been identified in many tissues including the
      central nervous system (CNS). We have previously demonstrated that injection of
      insulin directly into the cerebral ventricles (ICV) is followed by a drop in mean
      arterial pressure (MAP) associated with an increase in skeletal muscle blood
      flow. Given the similarities between the IGF-1 and insulin molecules and their
      respective receptors, we have investigated the effect of ICV administration of
      IGF-1 on systemic blood pressure and blood flow in selected vascular beds. ICV
      cannulas were implanted into normal rats and the animals were allowed to recover
      for 3 to 4 days. The femoral artery and vein were cannulated for blood pressure
      monitoring and blood sampling and blood flow probes placed around the iliac, the
      renal and the superior mesenteric artery were used to assess regional blood flow.
      ICV injection of IGF-1 resulted in a significant decrease in MAP with a nadir at
      15 minutes and a gradual return to baseline by 60 minutes; heart rate increased
      40 minutes after the injection. IGF-1 significantly enhanced vascular flow and
      conductance in the iliac, but not in the renal and superior mesenteric arteries.
      The effects of IGF-1 were much smaller than those observed previously with
      equimolar amounts of insulin. We conclude that IGF-1 can decrease MAP by
      selectively increasing blood flow to skeletal muscle through a direct action on
      the central nervous system.

PMID- 8738106
TI  - Asymptomatic cervical haemangioma treated by percutaneous vertebroplasty.
AB  - We report a 17-year-old asymptomatic patient with a partially collapsed seventh
      cervical vertebra due to a haemangioma revealed by conventional radiographs
      performed for army enrollment. Given radiological evidence of aggressiveness,
      percutaneous vertebroplasty by injection of methyl methacrylate cement was
      performed to prevent complications. CT a year later showed no progression of the
      lesion. The patient remains asymptomatic.

PMID- 8738108
TI  - Human glucagon receptor monoclonal antibodies: antagonism of glucagon action and
      use in receptor characterization.
AB  - This paper describes the development and characterization of the first monoclonal
      antibody specific for the recently cloned human glucagon receptor (hGR), and its
      use in probing receptor structure and function. We demonstrate specificity of one
      of the antibodies, CIV395.7A, by immunofluorescence staining and
      immunoprecipitation analysis. In addition, CIV395.7A specifically competes with
      glucagon for the hormone binding site on the receptor, indicating that the
      antibody's specific recognition epitope overlaps with the receptor's hormone
      binding domain. As a consequence, the mAB antagonizes glucagon-stimulated signal
      transduction as assayed by in vitro cAMP accumulation. Binding inhibition studies
      further reveal that the antibody specifically recognizes the human and rat GR,
      but not mouse. Using hGR/glucagon-like peptide I receptor chimeras, we have
      localized the recognition epitope of the antibody to the membrane-proximal half
      of the amino-terminal extension of the receptor, thus defining a domain on the
      receptor which is involved in glucagon binding.

PMID- 8738109
TI  - Effects of serotonin on the release of thyrotropin-releasing hormone from the rat
      retina in vitro.
AB  - Effects of serotonin on the release of thyrotropin-releasing hormone (TRH) from
      the rat retina were studied in vitro. The retina was incubated in medium 199 (pH
      7.4) with 1.0 mg/ml of bacitracin and 100 micrograms/ml of ascorbic acid (medium)
      for 20 min. The amount of TRH release into the medium was measured by
      radioimmunoassay. The TRH release from the rat retina was inhibited significantly
      in a dose-related manner with the addition of serotonin and enhanced with
      cyproheptadine. The inhibitory effect of serotonin on TRH release from the retina
      was blocked with the addition of cyproheptadine. The elution profile of methanol
      extract of the rat retina was identical to that of synthetic TRH. The findings
      suggest that the serotonergic system inhibits TRH release from the rat retina in
      vitro.

PMID- 8738110
TI  - Influence of zinc and selenium deficiency on parameters relating to thyroid
      hormone metabolism.
AB  - 48 weaned male Sprague-Dawley rats with an initial average body weight of 41 g
      were divided into 4 groups of 12 animals (zinc-deficient; zinc-adequate, pair-fed
      with zinc-deficient group; selenium-deficient; selenium-adequate) for 40 days.
      All groups were fed a semisynthetic diet with casein being the source of protein.
      In the selenium-deficient diet, there was a selenium concentration of 0.038
      mg/kg. The other diets were supplemented with Na-selenite in order to adjust the
      selenium concentration to 0.3 mg/kg. In the zinc-deficient diet, there was a zinc
      concentration of 4.1 mg/kg. The zinc concentrations in the other diets were
      adjusted to 45 mg/kg by the addition of zinc-sulfate heptahydrate. Zinc-deficient
      rats were characterized by a markedly reduced alkaline phosphatase activity in
      their serum, whilst selenium-deficient rats showed a markedly reduced glutathione
      peroxidase in serum proving their respective zinc-deficient and selenium
      deficient states. Zinc deficiency decreased concentrations of triiodothyronine
      (T3) and free thyroxine (fT4) in serum by approximately 30% when compared with
      zinc-adequate controls. The concentration of thyroxine (T4) in serum was not
      affected by zinc deficiency. Selenium-deficient animals had lower concentrations
      of T3 and T4 than selenium-adequate animals. The concentration of fT4 in serum
      was not affected by selenium deficiency. The activity of hepatic type I
      5'deiodinase was decreased by 67% by zinc deficiency and by 47% by selenium
      deficiency compared to adequate controls. The study data show that both zinc and
      selenium deficiency affect the metabolism of thyroid hormones.

PMID- 8738111
TI  - Captopril increases renin release stimulated by furosemide and hypotension in
      isolated perfused guinea pig kidneys.
AB  - To clearly understand the feedback mechanism of renin secretion by intrarenal
      angiotensin II synthesis, we studied the stimulatory effect of captopril, an
      angiotensin converting enzyme inhibitor, on renin release from the isolated
      perfused guinea pig kidneys. Captopril did not affect the basal renin secretion.
      Captopril increased on a dose dependent basis renin release induced by 0.1 mg/ml
      furosemide; 5.8 +/- 1.3 ng/ml/hr at 0 mg/ml of captopril vs. 8.8 +/- 1.6 ng/ml/hr
      at 0.01 mg/ml (p < 0.05) and 11.8 +/- 2.4 ng/ml/hr at 0.1 mg/ml (p < 0.01), 15-20
      min after furosemide infusion. After lowering the flow rates from 10 to 5 ml/min,
      renin secretion was not altered during the first 12 minutes. However, after
      adding 0.1 mg/ml captopril, renin secretion was enhanced within the following 8
      minutes (8.3 +/- 1.5 vs. 3.7 +/- 0.5 ng/ml/hr at the end of low flow rate period,
      p < 0.01). Lowering the perfusion flow of the guinea pig kidneys decreases the
      NaCl flux at the macula densa and also seems to have a similar effect to
      furosemide. Therefore, these effects of captopril suggest that intrarenal
      angiotensin II production has an important role in the regulation of renin
      secretion, probably via effects on the macula densa function.

PMID- 8738113
TI  - Is the growth hormone concentration regulated by the morning rise in the plasma
      cortisol concentration?
AB  - Exogenous steroids affect plasma growth hormone (GH) concentrations and
      hypothalamic somatostatin levels either directly, by stimulating the anterior
      pituitary gland, or indirectly by partially inhibiting the response of the
      pituitary gland to stimuli. The effect of the circadian rhythm of cortisol on
      plasma GH concentrations is unknown. In normal subjects, highest plasma GH
      concentrations are recorded within the first two hours of onset of sleep. During
      the early morning the plasma GH concentration decreases and the plasma cortisol
      concentration increases. We investigated the effect of the early morning rise in
      plasma cortisol concentration on plasma GH concentrations. We studied 12 healthy
      volunteers on two occasions. On one occasion the early morning rise in plasma
      cortisol concentrations was reduced by administering metyrapone (750 mg, 4 hourly
      from 03.00), while on the other occasion no intervention was made. Plasma GH and
      cortisol concentrations were measured every 30 and 60 minutes respectively from
      22.00 until 14.00. Metyrapone caused a significant reduction in the rise of
      plasma cortisol concentration, but the GH concentration was identical on both
      occasions. We conclude that the morning rise in cortisol concentration has no
      acute regulatory effect on the plasma GH concentration.

PMID- 8738112
TI  - Fish oil supplementation versus gemfibrozil treatment in hyperlipidemic NIDDM. A
      randomized crossover study.
AB  - To compare the impact of dietary fish oil supplementation (FO, 22 ml daily,
      containing 4.6 g of n-3 (omega-3) fatty acids, equalling 14.4 mmol) on
      carbohydrate and lipid metabolism with that of conventional lipostatic therapy
      (Gemfibrozil (G), 900 mg daily, equalling 3.6 mmol) on hyperlipidemic non-insulin
      dependent diabetes mellitus (NIDDM), 10 patients were selected for a randomized,
      short-time, cross-over study. Each patient was treated for a duration of 2 weeks,
      with an individual washout period of 8 weeks. Metabolic variables and intravenous
      glucose tolerances (1.2 mmol/kg body weight, t = 30 min) were determined on days
      1 and 15 of each treatment period. Plasma lipid concentrations were identical at
      baseline, but were reduced more markedly following G as against FO exposure (%
      change vs. baseline: total cholesterol (chol), - 13**/-6* (G vs FO: p = 0.05);
      total triglycerides (TG), -39**/-18** (p < 0.05); APO B, -17**/- 10* (N.S.); LDL
      chol, -15**/0 (p < 0.02); VLDL-chol, -50***/- 34*** (N.S.); VLDL-TG, -44***/-27**
      (N.S.); (p vs. baseline: * < 0.05, ** < 0.01, *** < 0.001). Total-HDL, HDL2, HDL3
      and APO A were not influenced by either FO or G. Neither FO nor G induced a
      change in intravenous glucose tolerances or associated basal and incremental
      concentrations of insulin and C-peptide. We concluded, based on short-time
      applications, that (a) neither treatment affected the carbohydrate metabolism in
      patients with NIDDM, and (b) a greater hypolipidemic efficacy had to be assigned
      to Gemfibrozil than to fish oil. It would therefore appear that Gemfibrozil acts
      as a useful lipostatic pharmacologic compound, whilst fish oil could serve as a
      potential ingredient of a prudent cardio-protective diet which favours the low
      plasma triglyceride concentrations found in NIDDM patients.

PMID- 8738114
TI  - The trouble about the 'third generation' pill.

PMID- 8738115
TI  - Comments on desogestrel and gestoden (3rd generation progestogens) and the
      incidence of thromboembolism.

PMID- 8738116
TI  - Blood glucose during hypothermia in the rat: dependence on the hypothermia
      induction way.

PMID- 8738117
TI  - The increased activity of angiotensin-converting enzyme in patients with diabetes
      and nephropathy.

PMID- 8738118
TI  - Do gastric inhibitory polypeptide and glucagon-like peptide-1 (7-36) amide
      contribute to the hyperinsulinaemia of pregnancy?

PMID- 8738119
TI  - The prepubertal ontogeny of galanin-like immunoreactivity in the male Meishan pig
      brain.
AB  - Galanin (GAL) is a neuropeptide found in the mammalian brain and is involved in
      numerous functions including the control of feeding, growth and reproduction, and
      therefore may be an important peptide to study in agricultural species. We
      describe the immunohistochemical localization of GAL throughout prepubertal
      development in the Meishan pig, a Chinese breed known for its superior
      reproductive characteristics, but slow growth rate and abundant adipose tissue.
      Brains of animals from gestational day (g) 30, 50, 70, 90 and 110 and postnatal
      day (pn) 1, 10, 20 and 50 (duration of pregnancy averaged 114 days) were
      processed using a standard immunohistochemical technique utilizing a commercially
      available rabbit anti-porcine GAL antibody. Galanin-like immunoreactivity (GAL
      IR) in cell bodies and fibers was evident in the brain at g30, primarily in the
      hypothalamus. Throughout prenatal development, cell bodies containing GAL-IR
      generally increased in number and distribution in the brain. During postnatal
      development, the number of cell bodies displaying GAL-IR decreased, particularly
      in hypothalamic areas. The distribution of GAL-IR in fibers became more
      widespread throughout gestational development, showing a pattern by pn1 that
      continued during later postnatal ages. The intensity of GAL-IR in fibers also
      increased throughout gestation. Some additional increases in immunoreactivity
      occurred postnatally, especially in the periventricular hypothalamus. The results
      of this study indicate that the distribution of GAL-IR in cell bodies and fibers
      in the Meishan pig brain was similar to that seen in other species, including the
      rat. These results support the hypothesis that GAL participates in the control of
      feeding, growth and reproduction in the pig.

PMID- 8738120
TI  - Transient expression of lyn gene in Purkinje cells during cerebellar development.
AB  - Expression of the lyn gene, a member of sarcoma proto-oncogene family, was
      analyzed immunohistochemically during cerebellar development in the rat. Lyn
      immunoreactivity was intense in axons, dendrites and somata of Purkinje cells
      from gestational day 18 to postnatal day 15 and then decreased. lyn gene
      expression clearly followed the appearance and the maturation of dendritic
      arbors. A rapid decrease in Lyn protein, after the 18th postnatal day, left only
      a few scattered positive Purkinje cell somata in the adult. External and
      undifferentiated internal granule cells were weak in Lyn immunoreactivity but
      gradually increased during development. Clusters of positive granule cells were
      found along the Purkinje cell layer with parasagittal bands crossing the granular
      layer by 21 days. These bands persisted into adulthood. Cerebellar nuclei lacked
      immunoreactivity in early development but only fastigial neurons began to acquire
      lyn gene expression by the 15th postnatal day. The corresponding appearance of
      the lyn gene expression and the formation of Purkinje cell dendritic arbors
      suggests that Lyn protein is involved in dendrogenesis. On the other hand, the
      late onset of immunoreactivity in fastigial neurons and granule cells implies a
      role in cell maintenance.

PMID- 8738121
TI  - Developmental changes in expression and distribution of the glutamate receptor
      channel delta 2 subunit according to the Purkinje cell maturation.
AB  - The glutamate receptor (GluR) channel delta 2 subunit is considered to be a
      functional molecule involved in motor coordination, Purkinje cell synapse
      formation and cerebellar long-term depression. We examined developmental changes
      in expression and distribution of the GluR delta 2 in the mouse cerebellum by in
      situ hybridization and immunohistochemistry. The GluR delta 2 mRNA was detected
      as early as embryonic day 15 (E15) in a cell mass consisting of Purkinje
      neuroblasts in the posterior cerebellum. During late embryonic and postnatal
      periods, the GluR delta 2 mRNA was expressed abundantly and specifically in
      Purkinje cells. By immunohistochemistry, immunoreactivity of the GluR delta 2 was
      found in both shafts and spines of Purkinje dendrites at early postnatal period.
      By P21, however, the intense immunoreactivity became restricted to the dendritic
      spines, especially along the postsynaptic membrane in contact with parallel fiber
      terminals. These findings suggested that the transcription of the GluR delta 2
      subunit occurs in the Purkinje cells from fetal through adult stage, but the
      intracellular localization of the protein products undergoes an alteration from
      non-synaptic to synaptic site when active synaptogenesis takes place.

PMID- 8738122
TI  - Long-term effects of neonatal maternal deprivation and ACTH on hippocampal
      mineralocorticoid and glucocorticoid receptors.
AB  - In the brain, corticosteroids bind to two types of receptors, the classical
      glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). The effects
      of different manipulations taking place during early ontogeny on GR and MR
      binding properties were examined in the adult hippocampus. Infant rats at
      postnatal day (pnd) 3 were deprived of maternal contact for 24 h and injected
      with saline or ACTH1-24 at the end of the deprivation period. They were then
      returned to their dams and weaned on pnd 21. At pnd 48, they were sacrificed (24
      h post adrenalectomy) and the hippocampal MR and GR measured using an in vitro
      cytosol binding assay. In the male rats, deprivation and deprivation + ACTH
      resulted in a reduction of GRs. MRs were also significantly down regulated in the
      deprived males. In the female rats, saline injections in deprived female rats
      resulted in increased GR capacity and ACTH injections led to a further up
      regulation of the GRs. None of the early manipulations influenced the regulation
      of the MRs in females. The binding affinity for corticosteroid receptors was also
      altered by some of the early manipulations. These results in adult (7-week-old)
      rats indicate that the receptor systems for corticosteroids in the brain are
      sensitive to brief manipulations occurring early in development. These changes in
      receptor capacity and/or affinity may affect corticosteroid-mediated processes in
      the adult rat.

PMID- 8738123
TI  - Development of divergence in dopamine responsiveness in genetically selected rat
      lines is preceded by changes in pituitary-adrenal activity.
AB  - Two pharmacogenetically selected Wistar rat lines have been used as a model for
      individual variability in behavioral and neuroendocrine responses. As a selection
      criterion the behavioral responsiveness for the dopamine agonist apomorphine was
      used, giving rise to the apomorphine-susceptible (apo-sus) and apomorphine
      unsusceptible (apo-unsus) rat lines. This selection has been maintained over 16
      generations. Recent studies have shown that adult rats of these selection lines
      also show pronounced differences in responsiveness of the hypothalamic-pituitary
      adrenal (HPA) system. In this study we analyzed to what extent the divergence in
      dopamine phenotype and HPA responsiveness, as observed in adult rats, are linked
      to possible differences, within both systems, during early postnatal development.
      Therefore, we measured in neonatal female rats of 10 and 18 days of age several
      parameters of the dopamine and HPA system which show significant differences in
      adult rats. These include tyrosine hydroxylase (TH) and dopamine D1 and D2
      receptor mRNA levels, which were determined within the nigrostriatal system since
      this system shows the most pronounced differences between adult rats of both
      selection lines. As indices of HPA activity we measured CRH mRNA, ACTH and total
      and free corticosterone plasma concentrations under basal conditions in the
      morning. Transcripts of the two types of corticosteroid receptors,
      mineralocorticoid (MR) and glucocorticoid (GR) receptor were measured in
      hippocampus and paraventricular nucleus. In 10-day-old rats all dopamine and HPA
      parameters were similar in rats of the two selection lines, except for GR mRNA in
      the parvocellular neurons of the paraventricular nucleus of the hypothalamus
      (PVN) of apo-sus rats, which was significantly higher than in apo-unsus rats.
      Eighteen-day-old apo-sus rats, however, showed significantly higher ACTH,
      comparable total corticosterone and a trend towards lower free corticosterone
      plasma levels. This HPA profile resembles the situation in adult apo-sus rats as
      compared with adult apo-unsus rats. Hippocampal GR mRNA expression and thymus
      weight were also higher in apo-sus rats. In addition, these rats showed an age
      related increase in hippocampal MR mRNA expression, while in apo-unsus rats MR
      mRNA levels did not change between pnd 10 and 18. The measures of the
      nigrostriatal dopamine system at day 18 were still similar in rats of both lines.
      In conclusion, divergence in the dopamine systems of the two pharmacogenetically
      selected rat lines emerges subsequent to divergence in pituitary-adrenal
      activity.

PMID- 8738125
TI  - The development of a species difference in the local distribution of brain
      estrogen receptive cells.
AB  - Estrogen receptors (ER) are crucial for estrogen-dependent brain differentiation
      and for estrogen-dependent neural functions of vertebrates. ER are expressed in a
      area-specific pattern in the vertebrate brain. The mechanisms that lead to the
      area-specific expression of ER are unknown. Here we use a species difference in
      the ER distribution between quail and chick and isochronic and isotopic quail to
      chick transplants to investigate mechanisms underlying the development of area
      specific expression of ER. The entire neural tube rostral to the 6th somite (n =
      2) or rostral to the otic capsules (n = 4) were transplanted at the second day of
      incubation (E2). In immunocytochemical stainings with the ER antibody H222Sp
      gamma, there is a defined cluster of intensely immunostained cells in the
      ventrolateral preoptic area of adult quails (the QERN). At the time of grafting,
      the entire brain primordium lacks ER. The QERN expresses ER as early as E13. The
      homologous area of the chicken brain does not differentiate cells that contain ER
      at any stage after ER are first detectable in the chicken brain at E11. In
      contrast, quail-chick chimeras develop the QERN phenotype in the ventrolateral
      preoptic area similar to quails. This implies that some signal which commits
      cells to the QERN phenotype (ER expression) is present in the quail brain
      primordium rostral to the otic capsules by embryonic day 2, and that this signal
      is unaffected by subsequent exposure to the global chick environment.

PMID- 8738124
TI  - Postnatal development of the dopamine transporter: a quantitative
      autoradiographic study.
AB  - The dopamine transporter performs an important role in regulating neurochemical
      transmission at dopaminergic synapses, as well as dopamine synthetic activity in
      dopaminergic neurons. Certain drugs and toxins exert effects at the transporter,
      especially cocaine, a common drug of abuse. We studied the development of these
      sites in the rat at postnatal ages day 0, 5, 10, 15, 21 and adult using
      quantitative autoradiography with the cocaine analogue [125I]RTI-55. At birth,
      certain structures such as the substantia nigra, interstitial nucleus of the
      medial longitudinal fasciculus, frontal and parietal cortex, and substantia
      inominata had [125I]RTI-55 binding levels that were already near the adult value.
      The striatum developed later, showing earlier growth in the anterior and
      dorsolateral regions, with early localization in both striosomes and a
      subcallosal streak. Anterior-to-posterior and lateral-to-medial gradients were
      present at day 0. The anterior striatum, ventral tegmental region, substantia
      nigra compacta and bed nucleus of the stria terminal is showed transient peaks in
      binding levels that were higher than the adult values. Structures showing
      relatively late development included the prefrontal cortex, nucleus accumbens
      shell, olfactory tubercle and subthalamic nucleus. Knowledge of the differential
      developmental patterns of the dopamine transporter in different brain regions may
      have implications for understanding the neurodevelopmental effects of prenatal
      cocaine exposure.

PMID- 8738126
TI  - Protective effects of maternal buspirone treatment on serotonin reuptake sites in
      ethanol-exposed offspring.
AB  - Previous work in this laboratory demonstrated that in utero ethanol exposure is
      associated with abnormal development of the serotonergic system. Specific
      abnormalities included deficiencies of serotonin (5-HT) and its metabolites, and
      cortical 5-HT reuptake sites. The concentration of 5-HT1A receptors was also
      altered. The serotonin deficit was detected in the fetal ethanol-exposed brain,
      at an age when 5-HT would normally function as an essential trophic factor. Thus,
      it was hypothesized that the early 5-HT ethanol-associated deficit of an
      essential trophic factor (e.g. 5-HT) could contribute to subsequent developmental
      abnormalities in serotonergic neurons. In the present investigation we used
      quantitative autoradiography (QAR) to more fully characterize the developmental
      abnormalities in 5-HT reuptake sites in developing offspring of ethanol-fed rats.
      In addition, we attempted to overcome the potential negative impact of the
      ethanol-associated deficit of fetal 5-HT, by administering a 5-HT1A agonist,
      buspirone, to pregnant rats. These investigations demonstrated that postnatal
      (PN) 19 and/or 35 day ethanol-exposed offspring had a significant decrease in
      [3H]citalopram binding to 5-HT reuptake sites in the frontal cortex, parietal
      cortex, lateral hypothalamus, substantia nigra, medial septum, and striatum. In
      contrast, [3H]citalopram binding was increased in the dorsal raphe on PN5 and in
      the median raphe on PN19. No significant ethanol-associated changes were detected
      in the hippocampus CA3 region or in the amygdala. When [3H]citalopram binding was
      compared in the offspring of saline- and buspirone-treated dams, it appeared that
      maternal treatment with buspirone prevented or reversed most of the ethanol
      associated developmental abnormalities in 5-HT reuptake sites. Buspirone
      prevented the decline in binding of [3H]citalopram in the frontal cortex, lateral
      hypothalamus, substantia nigra and medial septum. Similarly, buspirone treatment
      prevented the ethanol-associated increase in binding in the dorsal and median
      raphe. Additional experiments are needed to elucidate the impact of maternal
      buspirone treatment on the development of other neurotransmitter systems in
      offspring.

PMID- 8738127
TI  - Cholera toxin binds to differentiating neurons in the developing murine basal
      ganglia.
AB  - Cell-surface expression of gangliosides in the developing mammalian central
      nervous system is temporally-regulated in a cell-type and regionally specific
      fashion. Gangliosides may be involved in cell-cell and cell-matrix interactions,
      and can act synergystically with several growth factors or growth factor
      receptors. Thus, a role for gangliosides in the regulation of neuronal stem cell
      proliferation and differentiation has been suggested. We have previously shown
      that cholera toxin B subunit (CTB), which binds to the ganglioside GM1, binds
      heterogeneously to dissociated neuroepithelial cells from the developing mouse
      telencephalon. We stained fixed sections of the ganglionic eminences (GE) of
      fetal mouse brains and found that CTB labels regions which contain
      differentiating neurons, but does not stain the rapidly dividing neuroepithelial
      cells in the ventricular zone. We dissociated cells from the GE on day 14 of
      gestation (E14), labeled the cells with CTB-FITC, and separated them by flow
      cytometry. We found the highest level of CTB binding in postmitotic cells which
      had begun to express markers of neuronal differentiation. When CTB-sorted cells
      were placed into short-term (48 h) cell culture, high CTB binding continued to
      correlate with fewer numbers of proliferating cells and larger numbers of
      differentiating neurons. CTB binding and fluorescence activated cell sorting
      appear to be useful for separating populations of differentiating neurons from
      immature, proliferating cells. These studies further lead us to suggest that GM1
      plays a role in the differentiation of neurons in the basal ganglia.

PMID- 8738129
TI  - Apoptosis in the rostral migratory stream of the developing rat.
AB  - The rostral migratory stream consists of a large number of cells migrating from
      the lateral ventricles to the rostral telencephalon, primarily the olfactory
      bulb. The pathway continually provides neuro- and glioblasts throughout life. The
      present paper indicates that a considerable number of cells undergo apoptotic
      cell death en route, even in young (day 3) rats when presumably many vacant sites
      are still available in the developing brain.

PMID- 8738128
TI  - Immunohistochemical localization of insulin-like growth factor binding protein-5
      in the developing rat nervous system.
AB  - The insulin-like growth factors (IGF-I and IGF-II) are peptides with both growth
      promoting and insulin-like metabolic effects. The IGFs interact with and are
      modulated by a group of six IGF-binding proteins (IGFBP-1 through IGFBP-6).
      Previous studies have characterized IGFBP-5 and IGF-I gene expression in the
      developing nervous system. In the current study, cellular and tissue-specific
      distribution of IGFBP-5 protein was examined in the developing rodent nervous
      system using immunohistochemistry. Beginning with embryonic stage E12, IGFBP-5
      immunoreactivity was observed in peripheral nerves. This pattern persisted
      through adulthood and was detected within Schwann cells and axons after postnatal
      day 16 (P16). IGFBP-5 immunoreactivity first appeared in the CNS at P16. Purkinje
      cells of the cerebellum were immunostained at P16, P32 and in the adult. IGFBP-5
      immunoreactivity was also detected in several brain stem nuclei and their
      corresponding tracts as well as neuroglia. Nerve tracts and glia in the postnatal
      spinal cord were also immunopositive, however, spinal cord neurons were not
      stained. The current results, coupled with the known profile of IGF-I expression
      during nervous system development demonstrates the colocalization of IGF-I and
      IGFBP-5 in PNS, cerebellum, and brain stem.

PMID- 8738131
TI  - Corticosteroid actions on the expression of kainate receptor subunit mRNAs in rat
      hippocampus.
AB  - Previous studies have shown that corticosteroid hormones affect kainate-induced
      excitotoxic processes in the rat hippocampus. In the present study we employed in
      situ hybridization to examine the effect of adrenalectomy, and subsequent
      treatment with a low or a high lose of corticosterone on the mRNA levels for
      kainate receptor subunits in the hippocampus. We observed that adrenalectomy by
      itself does not affect the expression pattern for the GluR6, GluR7, KAR1 and KAR2
      subunits. However, treatment of the adrenalectomized animals with a low dose of
      corticosterone (3 micrograms/100 g bodyweight) resulted in an enhanced expression
      of the KAR1, KAR2 and GluR6 subunit mRNAs, when compared to the expression levels
      in the untreated rats or the sham operated controls. Treatment with a high dose
      of corticosterone (1 mg/100 g bodyweight) yielded expression levels which were
      significantly lower than those observed in animals treated with a low
      corticosterone dose, for the KAR1, KAR2 and GluR7 subunit mRNAs; the levels did
      not differ from those in untreated rats or in the sham group. We conclude that
      changes in corticosteroid receptor occupancy, which may occur daily due to
      circadian or stress-induced variations in the circulating corticosterone level,
      potentially regulate high affinity kainate receptor activation and the processes
      in which these receptors are involved.

PMID- 8738130
TI  - Characterization of chicken protein tyrosine phosphatase alpha and its expression
      in the central nervous system.
AB  - Protein tyrosine phosphorylation and dephosphorylation are important in cell
      proliferation, differentiation and functioning of the central nervous system. We
      have identified a cDNA clone encoding a new transmembrane protein tyrosine
      phosphatase from a chicken brain cDNA library. The predicted amino acid sequence
      contains two phosphatase tandem repeats in the intracellular domain and multiple
      glycosylation sites in the extracellular domain. Since its intracellular domain
      shares 94% identity with human PTP alpha, we call it chicken PTP alpha (ChPTP
      alpha). Antibodies specific to ChPTP alpha recognize two major protein bands at
      130 and 85 kDa in immunoblot and immunoprecipitation. ChPTP alpha transcript and
      protein are found in many tissues, but they are particularly abundant in brain.
      To gain insight into the function of PTP alpha s, we investigated the cell-type
      specific localization of ChPTP alpha in cerebellum by in situ hybridization and
      immunostaining. Throughout development, the level of ChPTP alpha remains similar
      from embryonic day 7 to post-hatching day 14, but the abundance and distribution
      of cells expressing this protein vary systematically through this period. During
      development, ChPTP alpha appears in pre-migratory and migrating granule cells,
      and in Bergmann glia and their radial processes. By 2-weeks after hatching, ChPTP
      alpha disappears from all cells of the cerebellum except Bergmann glia. Our data,
      which show for the first time the temporal and spacial distribution of a PTP
      alpha, suggest that these transmembrane phosphatases are important in the
      differentiation and function of Bergmann glia and in the migration of granule
      cells, and thereby play a role in development of the cerebellum.

PMID- 8738132
TI  - Photic regulation of c-fos gene expression in the suprachiasmatic nucleus and the
      circadian rhythm of photosensitivity in the mink.
AB  - The relationship between the photic stimulation of the c-fos gene product in
      cells of the suprachiasmatic nuclei and the photoperiodic control of testicular
      activity were examined in mink. Mink were kept in a short photoperiod (control,
      LD4:20), or in 'asymmetric skeleton photoperiods' (groups A and B). The light
      period for groups A and B was divided into two fractions (3 h 30 min and 30 min);
      the shorter fraction occurred in the night, 4 h (group A) or 8 h (group B) after
      the end of the main light period. There was no photic activation of the proto
      oncogene c-fos on the control or group A, and 4 weeks on this photoperiodic
      treatment produced marked testicular development. In contrast, in group B, c-fos
      mRNA was induced 30 min after the end of the secondary photofraction, was maximal
      30 min later and then decreased. Fos-like immunoreactivity was detected 2 h after
      the end of the secondary photofraction, with activity peaking 1 h later. The
      animals of this group remained sexually quiescent. These results suggest that
      photo-induction of the proto-oncogene c-fos is implicated in the gonadal
      inhibition induced in this species when the light period, extends into the
      photosensitive phase of the circadian rhythm of photosensitivity.

PMID- 8738133
TI  - Immortalization of neuroendocrine pinealocytes from transgenic mice by targeted
      tumorigenesis using the tryptophan hydroxylase promoter.
AB  - Tryptophan hydroxylase (TPH) is the first enzyme in both serotonin and melatonin
      biosynthesis in neuroendocrine cells of the pineal gland. The lack of
      immortalized neuroendocrine pineal cell lines has been a major obstacle to the
      study of the tissue-specific and circadian regulation of TPH gene expression in
      the pineal gland. Previously, we demonstrated that a 6.1 kb 5' upstream region of
      the mouse TPH gene directs the restricted expression of a lacZ reporter gene to
      the pineal gland and the raphe nuclei of transgenic mice. Therefore, to develop
      TPH-expressing pineal cell lines we first established transgenic mice carrying a
      construct consisting of 6.1 kb of 5' flanking region fused to the SV40 T-antigen.
      These animals developed highly invasive pineal tumors and died at 12-15 weeks of
      age. The pineal tumors obtained from the transgenic mice were utilized to
      establish the immortalized pinealocyte-derived cell lines. These cells express
      two marker enzymes, TPH and serotonin N-acetyltransferase (NAT). In pineal gland
      TPH and NAT expressions have been known to be regulated during circadian cycle.
      The two established cell lines therefore promise to be a valuable in vitro model
      system for the study of the rhythmic nature of the pineal function at molecular
      level in mammal.

PMID- 8738134
TI  - Characterization of an L-type calcium channel expressed by human retinal Muller
      (glial) cells.
AB  - The traditional notion that glial cells are permeable only to potassium has been
      revised. For example, glia from various parts of the nervous system have calcium
      permeable ion channels. Since characterization of the calcium channels in glia is
      limited, the purpose of this study was to determine the molecular identity and
      examine the functional properties of a voltage-gated calcium channel expressed by
      Muller cells, the predominant glia of the retina. Whole-cell and perforated-patch
      recordings of human Muller cells in culture revealed a high threshold voltage
      activated calcium current that is blocked by dihydropyridines, but not by omega
      conotoxin GVIA or omega-conotoxin MVIIC. RT-PCR of cultured human Muller cells
      using primers specific for the calcium channel subunits demonstrated the
      expression of an L-type channel composed of the alpha 1D, alpha 2 and beta 3
      subunits. The alpha 2 subunit of the Muller cell calcium channel is a splice
      variant which is distinct from either the skeletal muscle alpha 2s or the brain
      alpha 2b. Our electrophysiological experiments indicate that the alpha 1D/alpha
      2/beta 3 calcium channel is functionally linked with the activation of a
      potassium channel that may serve as one of the pathways for the redistribution by
      Muller cells of excess retinal potassium.

PMID- 8738135
TI  - Differential subcellular localization of SNAP-25a and SNAP-25b RNA transcripts in
      spinal motoneurons and plasticity in expression after nerve injury.
AB  - Synaptosomal-associated protein of 25 kDa (SNAP-25) is involved in the molecular
      regulation of neurotransmitter release. SNAP-25 exists in two isoforms, which
      arise from alternative splicing of exon 5. In situ hybridization was used to
      examine whether SNAP-25 isoform mRNA expression may be altered by experimental
      manipulations. The effect of unilateral nerve injury on SNAP-25 mRNA levels was
      studied in motoneurons of the rat lumbar spinal cord. In all animals, SNAP-25a
      RNA transcripts were demonstrated in the nucleus of motoneurons, whereas SNAP-25b
      mRNA was present mainly in the cytoplasm. Cloning of the rat Snap gene intron
      spacing the alternative exon 5a and 5b sequences and generation of an intron
      specific oligonucleotide probe used for in situ hybridization did not point to
      the presence of unspliced variants of SNAP-25b mRNA. After unilateral sciatic
      nerve transection (axotomy), SNAP-25a and SNAP-25b expression decreased in
      axotomized motoneurons compared with corresponding motoneurons on the unlesioned
      side. A significant decrease was demonstrated 2 days after axotomy, which reached
      a maximum after 7 days (62% for SNAP-25a and 67% for SNAP-25b), while levels had
      slightly recovered by 14 and 28 days. Ventral root avulsion also induced a
      decrease in levels of SNAP-25 RNA transcripts, suggesting that the axonal injury
      in itself was responsible for the down-regulation of Snap gene expression. This
      study shows that, in spinal motoneurons, SNAP-25a and SNAP-25b RNA transcripts
      have different subcellular localization and that levels of SNAP-25 RNA
      transcripts are down-regulated after axonal injury.

PMID- 8738136
TI  - Cloning of focal adhesion kinase, pp125FAK, from rat brain reveals multiple
      transcripts with different patterns of expression.
AB  - Focal adhesion kinase (pp125FAK, or FAK) is a cytoplasmic tyrosine kinase
      enriched in focal adhesions. We have screened a rat striatum cDNA library with a
      PCR-amplified cDNA probe specific for FAK messenger. Sequencing of multiple
      clones revealed the existence of three different 5'-leader sequences resulting
      from the combination of 5 conserved boxes. One of them contains a potential
      alternative initiation site, 78 base pairs upstream of that previously described.
      Another is 89% identical to a human genomic sequence located on chromosome 3.
      Most positive clones contained an insertion coding for three amino acids (Pro-Trp
      Arg) in the region responsible for focal adhesion targeting. We propose to name
      this variant of the protein FAK +. The pattern of expression of the multiple
      forms of FAK was studied by RT-PCR and Southern hybridization with specific
      primers and probes. The different 5'-leader sequences were always found in the
      same proportions. In contrast, FAK + mRNA was found at very low levels in non
      nervous tissues, whereas it was highly expressed in all brain regions. In cells
      in culture, it was present in astrocytes and enriched in neurons. These results
      demonstrate the existence of multiple forms of FAK transcript and protein, one of
      which, FAK +, may play a specific role in the nervous system.

PMID- 8738137
TI  - Sequence analysis and immunolocalisation of phosphatidylethanolamine binding
      protein (PBP) in human brain tissue.
AB  - We have cloned and sequenced cDNA corresponding to human brain
      phosphatidylethanolamine binding protein (PBP) and have used the resultant data
      to generate PBP-specific anti-peptide antisera for immunohistochemical studies.
      The distribution of PBP was assessed immunohistochemically in sections from
      multiple regions of neonatal brain and spinal cord, including spinal nerve roots.
      Strong PBP immunoreactivity was present in the cytoplasm of oligodendrocytes in
      the white matter and Schwann cells in the nerve roots. There was only weak
      immunostaining within the neurones and neuropil. The findings are in keeping with
      a role for PBP in the organisation of phospholipids in the myelin sheath.

PMID- 8738138
TI  - Chromosomal localization of the neurological mouse mutations tottering (tg),
      Purkinje cell degeneration (pcd), and nervous (nr).
AB  - We have refined the map positions and identified molecular markers for three
      neurological mutations in the mouse, tottering (tg), Purkinje cell degeneration
      (pcd), and nervous (nr). These mutations were localized using simple sequence
      length polymorphisms between the mouse strain on which the mutation arose and the
      inbred strain onto which the mutation was bred. This approach to mutation mapping
      is generalizable to any mutant that has been backcrossed for several generations.
      The tg mutation was localized to the 1.1 cM region of chromosome 8 distal to
      simple sequence repeat (SSR) D8Mit103 and proximal to SSRs D8Mit79, D8Mit105, and
      D8Mit283. The pcd locus was mapped to the 5 cM interval of chromosome 13 between
      SSRs D13Mit139 and D13Mit67, and the nr locus was mapped between SSRs D8Mit155
      and D8Mit18, a 5.6 cM region of chromosome 8. For each mutation, several SSRs
      distinguishing mutant from wild type chromosomes were identified within these
      regions. The definition of molecular markers distinguishing mutant from wild type
      alleles makes possible for the first time identification of tg, pcd, and nr
      mutants prior to behavioral manifestation of the mutant genotype. Thus,
      developmental studies of these mutants designed to describe or dissect the
      biochemical basis of the induction of the mutant phenotype are now feasible.

PMID- 8738139
TI  - Sense and antisense transcripts of the developmentally regulated murine hsp70.2
      gene are expressed in distinct and only partially overlapping areas in the adult
      brain.
AB  - We have examined the spatial pattern of expression of a member of the hsp70 gene
      family, hsp70.2, in the mouse central nervous system. Surprisingly, RNA blot
      analysis and in situ hybridization revealed abundant expression of an 'antisense'
      hsp70.2 transcript in several areas of adult mouse brain. Two different
      transcripts recognized by sense and antisense riboprobes for the hsp70.2 gene
      were expressed in distinct and only partially overlapping neuronal populations.
      RNA blot analysis revealed low levels of the 2.7 kb transcript of hsp70.2 in
      several areas of the brain, with highest signal in the hippocampus. Abundant
      expression of a slightly larger (approximately 2.8 kb) 'antisense' transcript was
      detected in several brain regions, notably in the brainstem, cerebellum,
      mesencephalic tectum, thalamus, cortex, and hippocampus. In situ hybridization
      revealed that the sense and antisense transcripts were both predominantly
      neuronal and localized to the same cell types in the granular layer of the
      cerebellum, trapezoid nucleus of the superior olivary complex, locus coeruleus
      and hippocampus. The hsp70.2 antisense transcripts were particularly abundant in
      the frontal cortex, dentate gyrus, subthalamic nucleus, zona incerta, superior
      and inferior colliculi, central gray, brainstem, and cerebellar Purkinje cells.
      Our findings have revealed a distinct cellular and spatial localization of both
      sense and antisense transcripts, demonstrating a new level of complexity in the
      function of the heat shock genes.

PMID- 8738140
TI  - Characterization of the structure and function of the gene for transcription
      factor BF-1, an essential regulator of forebrain development.
AB  - Brain factor-1 (BF-1) is a winged-helix transcription factor which has been shown
      to be essential for the development of the cerebral hemispheres. We report here
      the cloning and characterization of the mouse BF-1 gene. We have identified two
      classes of alternatively spliced mouse BF-1 cDNA which are transcribed from
      distinct promoters. Both classes of cDNA encode identical BF-1 proteins. The
      class 1 mouse cDNA is the homolog of the previously reported rat and human BF-1
      cDNAs, and accounts for about 90-95% of BF-1 expression in brain. Primer
      extension analyses show that the major promoter, P1, is TATA-less and has
      multiple transcription start sites. We identified neural cell lines which express
      BF-1 primarily from the P1 promoter, including the OBL21a and OBL21 cell lines
      derived from the olfactory bulb. Expression of BF-1 is highest in proliferating
      OBL21 cells, declining as the cells differentiate in vitro. This correlates well
      with the reduction of BF-1 expression as the cells of the telencephalic
      neuroepithelium differentiate. Using these cells, we demonstrate that the genomic
      region between -3.7kb and -79 bp upstream of the P1 promoter contains cell
      specific enhancer activity in transient transfection assays.

PMID- 8738141
TI  - Fenfluramine-induced activation of the immediate-early gene c-fos in the
      striatum: possible interaction between serotonin and dopamine.
AB  - DL-Fenfluramine, a serotonin (5-HT) releasing agent, induces rapid expression of
      Fos-like immunoreactivity (Fos-LI) in the striatum as well as in other brain
      structures receiving a dense 5-HT innervation. Fenfluramine-induced Fos-LI
      expression in the striatum may result directly from the activation of 5-HT
      receptors or may be the result of interactions between dopamine (DA) and 5-HT
      neurotransmitter systems. To discriminate between these two possibilities,
      various groups of rats were pretreated with different 5-HT antagonists or a DA D1
      antagonist, 20 min before fenfluramine administration. Animals were killed 60 min
      later. In the striatum, fenfluramine-induced expression of Fos-LI was almost
      completely blocked by SCH 23390, methysergide and S(-)-propranolol. The immediate
      early gene response to fenfluramine was only slightly affected by pretreatment
      with the 5-HT2A/2C antagonist ritanserin. Fenfluramine was also administered to
      sham-operated and to unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. In
      the 6-OHDA-lesioned rats, fen-fluramine-induced Fos-LI was decreased by 60% on
      the DA denervated side compared to the intact side and to sham-operated rats. To
      further probe the possibility of a direct activation of Fos-LI by 5-HT receptor
      subtypes, we evaluated the expression of Fos-LI after the administration of
      different 5-HT agonists. Our results demonstrate that neither 8-OH-DPAT, CGS
      12066B, RU 24969 nor phenyl-biguanide was able to reproduce the effects of
      fenfluramine. Only a high dose of DOI (8.5 mg/kg) produced a moderate expression
      of Fos-LI in the dorsomedial part of the striatum. This contrasted with the Fos
      LI expression in other brain areas where 8-OH-DPAT and DOI (2.5 and 8.5 mg/kg)
      reproduced the effects of the 5-HT releasing agent. Our results suggest that the
      release of 5-HT by fenfluramine induced Fos-LI expression predominantly in a
      striatal region related to associative functions and, that this c-fos response
      may be under the control of both 5-HT and DA. Moreover, the mechanism by which
      fenfluramine induces c-fos expression in the striatum differs from other brain
      regions.

PMID- 8738142
TI  - Channel activators reduce the expression of sodium channel alpha-subunit mRNA in
      developing neurons.
AB  - The expression of rat brain sodium channel alpha-subunit (Na+I, Na+II and Na+III)
      and beta 1-subunit mRNAs was examined in rat fetal brain neurons in culture. A
      combined technique of reverse transcription and polymerase chain reaction (RT
      PCR) was used. Two different PCR primer sets were designed to obtain simultaneous
      amplification of the three alpha-subunit mRNAs. All three molecules were detected
      in fetal neurons but the expression pattern (Na+III > Na+II > > Na+I) was
      different than that observed in adult tissue (Na+II > Na+I > Na+III). Expression
      of the beta 1-subunit mRNA was detected using a specific PCR primer set. Doublet
      bands were amplified, from fetal cells and adult brain mRNA. To get further
      insight into the molecular mechanism that underlie activity dependent plasticity
      of sodium channels, we studied the effect on the expression of sodium channel
      subunits mRNA of a 60 h incubation of cells in the presence of a scorpion
      neurotoxin that blocks channel inactivation. An overall decrease in the
      expression of all three alpha-subunit mRNAs was observed whereas the beta 1
      subunit mRNA was unaffected by the same treatment. When cells were incubated with
      the scorpion neurotoxin together with tetrodotoxin, to block Na+ influx through
      channels, the decrease in mRNA expression was not observed. Finally, a 60 h
      continuous depolarization of cells induced by application of a high concentration
      KC1 solution did not mimic the effect of the scorpion toxin. These observations
      suggest that a persistent activation of the sodium channels is able to down
      regulate mRNA expression for alpha-subunits but not for the beta 1-subunit.

PMID- 8738143
TI  - Protein kinase C isoforms and cell proliferation in neuroblastoma cells.
AB  - The expression of protein kinase C isoforms in the neuroblastoma cell line Neuro
      2a has been studied. It is shown that Neuro 2a cells express alpha, delta,
      epsilon and zeta PKCs. Inhibition of cell proliferation by using protein kinase C
      inhibitors (H7 or calphostin C) or medium without glutamine affects markedly the
      pattern of PKC isoforms. All treatments reduced significantly (50-70%) the
      content of PKC alpha. None of the treatments altered PKC zeta or epsilon. The
      content of PKC delta was increased (88-120%) in cells treated with PKC inhibitors
      but was slightly reduced in cells incubated in medium without glutamine. However,
      none of the treatments affected the content of the corresponding mRNAs. Long-term
      treatment of synchronized cells with the phorbol ester PMA depletes PKC alpha but
      not PKC delta or zeta and only partially PKC epsilon. This treatment with PMA did
      not affect DNA synthesis, indicating that PKC alpha does not play a significant
      role in the control of proliferation of these cells.

PMID- 8738144
TI  - Regionally and temporally distinct patterns of induction of c-fos, c-jun and junB
      mRNAs following experimental brain injury in the rat.
AB  - Lateral (parasagittal) fluid-percussion brain injury of mild (1.0-1.5 atm) and
      moderate (2.1-2.4 atm) severity induced expression of mRNAs for the immediate
      early genes (IEGs) c-fos, c-jun and junB. At 5 min following mild brain injury, c
      fos and junB mRNA were co-induced in the cortex ipsilateral to the impact site.
      Expression remained elevated up to 2 h after injury and returned to control
      levels by 6 h. Levels of c-fos mRNA increased in the cells of the hippocampal
      dentate gyrus as early as 5 min after mild brain injury and additionally in the
      areas CA1-3 by 30 min. By 2 h, no hippocampal c-fos mRNA was detectable.
      Induction of junB mRNA in the hippocampus was delayed, occurring at 30 min after
      injury, and remained elevated up to 2 h post injury. Increased levels of junB
      mRNA were also observed in the striatum ipsilateral to the injury. Increased
      expression of c-jun mRNA was restricted to the ipsilateral dentate gyrus and was
      observed at 5 min after injury and remained elevated up to 6 h. Although the
      temporal pattern of induction of individual IEGs after brain injury of moderate
      severity was similar to that observed after mild severity, moderate injury
      induced IEG mRNA in both injured and contralateral hemispheres. These data
      suggest that traumatic brain injury invokes a complex acute regional and cellular
      response which may involve the activation of multiple signal transduction
      pathways.

PMID- 8738145
TI  - Radial maze performance, open-field and elevated plus-maze behaviors in Fyn
      kinase deficient mice: further evidence for increased fearfulness.
AB  - Fyn-deficient mice produced by inserting the beta-galactosidase gene (lacZ) into
      the fyn gene locus were tested in a radial maze, an open field and an elevated
      plus-maze. In the radial maze, the homozygous Fyn-deficient (fynz/fynz) mice
      showed no impairment in spatial learning, although they showed a stronger
      avoidance tendency for those arms located closer to the experimenter during
      pretraining (adaptation). In the open-field test, the fynz/fynz mice defecated
      more frequently in the bright condition than did the +/fynz mice, and they were
      less active during the first 10-min test period than the +/fynz mice. In
      addition, the temporal pattern of locomotor activity for fynz/fynz mice was
      altered by changing the illumination while the pattern for +/fynz mice remained
      relatively unchanged. Scores reflecting the fear-response in the elevated plus
      maze were higher in the fynz/fynz mice. These results indicate that Fyn
      deficiency increased fear-response, but did not impair spatial learning in the
      radial maze. It is suggested that we should take account of effects of emotional
      factors in the learning experiment using mutant mice.

PMID- 8738146
TI  - Two types of amyloid precursor protein (APP) mRNA in rat glioma cell lines:
      upregulation via a cyclic AMP-dependent pathway.
AB  - APP is a multifunctional transmembrane glycoprotein and the only known natural
      source of beta A4 peptide-the major constituent of senile plaques in Alzheimer's
      disease (AD). The expression and cAMP-dependent regulation of the APP gene were
      investigated in primary cultures of rat astrocytes and two related glioma cell
      lines, BT4C and BT4Cn, which exhibit distinct invasive phenotypes. Besides the
      well-characterized 3.5 kb APP mRNA class, a robust expression of an unusual 2.8
      kb APP mRNA class was revealed by Northern blotting in both glioma cell lines,
      but not in the astrocytes. Low amounts of the 2.8 kb APP mRNA species were also
      observed in rat liver and occasionally in aged rat brain. The 2.8 kb APP mRNA
      contained exons 1-18 and may thus be generated by truncation of the 3'
      untranslated region. For the first time, regulation of the APP gene via a cAMP
      dependent mechanism was shown. Exposure to dBcAMP dramatically upregulated the
      3.5 and 2.8 kb transcripts in BT4C cells, and, to a lesser extent, in BT4Cn cells
      where the constitutive expression of the APP gene was much higher. Elucidation of
      the factors involved in cAMP-dependent induction of APP mRNA in these cells may
      shed more light on the molecular mechanisms of APP overexpression.

PMID- 8738147
TI  - Use of a high stringency differential display screen for identification of
      retinal mRNAs that are regulated by a circadian clock.
AB  - We report here the initiation of a systematic screen to identify clock-controlled
      mRNAs from the retina of Xenopus laevis using mRNA differential display. Xenopus
      retina contains an endogenous circadian clock located within the photoreceptor
      layer. The retinal block controls many aspects of physiology, including gene
      transcription. This screen uses differential display, a PCR based procedure, to
      compare retinal mRNA populations at different times of day in constant darkness,
      for identification of messages that exhibit rhythmic expression. Out of approx.
      2000 mRNAs that we have screened to date, we have identified four candidates for
      clock-controlled mRNAs. Initial characterization of one of these PCR products
      shows that it recognizes a pair of mRNA bands on Northern blots that exhibit high
      amplitude rhythms. This pair of messages is called RM1 and shows peak levels of
      expression in the subjective night. In situ hybridization shows that this clock
      controlled message is specifically localized to the clock containing
      photoreceptor cell layer within the retina. Identification of new messages that
      are under the control of the circadian clock has broad relevance in retinal
      physiology and provides an opportunity to gain insight into the molecular
      mechanism of vertebrate circadian control.

PMID- 8738148
TI  - Regenerating sensory neurones of diabetic rats express reduced levels of mRNA for
      GAP-43, gamma-preprotachykinin and the nerve growth factor receptors, trkA and
      p75NGFR.
AB  - Nerve growth factor (NGF) is considered to play a role in neurite outgrowth of
      small nerve fibres which express its high-affinity receptor, trkA. Nerve
      regeneration is delayed in diabetes mellitus following an experimental crush
      injury. In steady-state (i.e., in the absence of axotomy) diabetic rats also show
      reduced expression of NGF in certain target tissues. This study was designed to
      measure expression of messenger RNA (mRNA) coding for NGF and its receptors, trkA
      and p75NGFR, during nerve regeneration and degeneration in rats with
      streptozotocin-induced diabetes; mRNA coding for preprotachykinin A (the
      substance P precursor), whose expression is stimulated by NGF, and mRNA for
      growth-associated protein-43 (GAP-43) were also measured in blots from L4 + L5
      (pooled unilaterally) dorsal root ganglia. Unexpectedly, distal stumps of
      diabetic injured sciatic nerve contained higher levels of NGF mRNA than those of
      control rats. In ipsilateral dorsal root ganglia of control animals, mRNA for
      trkA and preprotachykinin A were decreased and GAP-43 mRNA increased after nerve
      injury; mRNA for p75NGFR was decreased only 3 weeks after nerve transection. In
      diabetic rats, the levels of all of these mRNA, both in intact and lesioned
      dorsal root ganglia, were lower than those from control rats. These results
      suggest that regenerating sensory neurones of diabetic rats receive less NGF
      support in spite of enhanced NGF mRNA levels in distal stumps compared to non
      diabetic rats. Reduced expression of its high-affinity receptor, trkA, in ganglia
      of diabetic rats might explain this discrepancy.

PMID- 8738149
TI  - Age-related changes in the expression of corticotropin-releasing hormone receptor
      mRNA in the rat pituitary.
AB  - Hypothalamic corticotropin releasing hormone (CRH) controls the release of
      adrenocorticotrophic hormone (ACTH) from the pituitary and, and therefore has a
      major role in the activation of the hypothalamic-pituitary-adrenal (HPA) axis.
      The HPA axis function has been shown to be impaired in the neonatal period as
      well as in aging. Since corticotropin-releasing hormone receptor (CRHr) plays a
      crucial role in the regulation of HPA axis, using in situ hybridization
      histochemistry we have analyzed the rat pituitary for the presence of CRHr mRNA
      in the neonatal period and during aging. The results show an increase in CRHr
      mRNA in 3-day-old rats, with a progressive increase within the first month. In
      the aging rat, we observed a down-regulation of the CRHr mRNA localized in the
      anterior pituitary, gland viceversa, an increased signal in the intermediate
      lobe. Our findings demonstrate age-related changes in the expression of the CRHr
      mRNA in the pituitary, with a differential regulation in the anterior and
      intermediate lobes of aging rats.

PMID- 8738150
TI  - Metabolism of neuropeptide Y and calcitonin gene-related peptide by cultivated
      neurons and glial cells.
AB  - Neuropeptide Y and calcitonin gene-related peptide are abundant neuropeptides in
      the mammalian central and peripheral nervous systems. Their enzymatic degradation
      by cultivated neurons, astrocytes, and microglia, as well as by purified
      urokinase-type plasminogen activator, plasmin, thrombin, and trypsin, was
      investigated in an in vitro approach to elucidate the role of matrix-degrading
      serine proteinases for inactivation of neuropeptides, especially those of higher
      amino acid chain length, in the brain. Astrocytes were almost unable to
      catabolize the peptides. Cultivated neurons and microglia digested neuropeptide Y
      through cleavage after Arg19, Arg25, Arg33, and Arg35, calcitonin gene-related
      peptide was cleaved after Arg11 and Arg18. The same cleavage pattern was
      observed, when neuropeptide Y and calcitonin gene-related peptide were degraded
      by purified urokinase-type plasminogen activator, plasmin, thrombin, and trypsin.
      For further characterization of the neuropeptide-degrading serine proteinase
      activities from cell cultures, urokinase-type plasminogen activator was
      identified on microglia by immunostaining, whereas tissue-type plasminogen
      activator mRNA occurred in neurons and astrocytes, but not in microglia. The data
      are consistent with the possibility that the neuropeptide-degrading serine
      proteinase activity on neurons and microglia is due to a mixture of plasmin and
      plasminogen activator activities.

PMID- 8738151
TI  - Localization of AT2 angiotensin II receptor gene expression in rat brain by in
      situ hybridization histochemistry.
AB  - To localize the gene expression of AT2 angiotensin II receptors in rat brain we
      performed in situ hybridization histochemistry using 35S-labeled antisense
      riboprobes. The AT2 receptor mRNA expression pattern was compared in consecutive
      brain sections, from 2 week old rats, with the receptor expression by means of
      [125I]Sar1-ANG II binding and displacement with AT2 selective ligands followed by
      autoradiography. Expression of AT2 receptor mRNA was found in several thalamic
      nuclei (ventral posterolateral, mediodorsal, central medial, paracentral, and
      paraventricular), the medial geniculate nuclei, the nucleus of the optic tract,
      the subthalamic nucleus, the interposed nucleus of the cerebellum, and in the
      inferior olive. In these areas the AT2 receptor gene expression corresponds well
      with [125I]Sar1-ANG II binding. In addition, AT2 receptor mRNA expression was
      found in the red nucleus where no [125I]Sar1-ANG II binding was present. No
      significant hybridization of the AT2 receptor antisense probe was found in septal
      nuclei, the locus coeruleus, the dorsolateral geniculate nucleus, or the
      cerebellar cortex, areas rich in [125I]Sar1-ANG II binding. Our results indicate
      that some brain regions may be involved in AT2 receptor formation, transporting
      the receptor protein to other brain areas. However, in most structures, both the
      formation and expression of receptors occur, suggesting the existence of local
      AT2 receptor circuits, or that of AT2 autoreceptors. Other structures express
      only the receptor protein, indicating that these AT2 receptors are produced
      elsewhere. Our present data are the basis for further studies on the
      clarification of AT2 receptor pathways in the brain.

PMID- 8738152
TI  - Heme oxygenase-1 (HO-1) protein induction in rat brain following focal ischemia.
AB  - The induction of the heme oxygenase-1 (HO-1) protein, also called HSP32, was
      compared to HSP70 heat shock protein induction following focal ischemia. Adult
      Sprague-Dawley male rats (n = 14) were subjected to either 30 min or 2 h of focal
      cerebral ischemia using the suture, middle-cerebral-artery (MCA) occlusion model.
      Controls (n = 4) had sham surgery. Following 24 h of reperfusion, subjects were
      killed and their brains stained immunocytochemically for HO-1 and the HSP70 heat
      shock proteins. One day following 30 min of ischemia, HO-1 and HSP70 staining in
      striatum occurred mainly in endothelial cells in infarcts and in glial cells
      surrounding the areas of infarction. Following the 30 min ischemia HO-1 was not
      induced in cortex whereas HSP70 was induced in cortical neurons in the MCA
      distribution. One day following 2 h of MCA ischemia, both HO-1 and HSP70 were
      induced in neurons in cortex in the MCA distribution. HO-1, however, was induced
      in glial cells throughout ipsilateral cortex, inside as well as outside the MCA
      distribution. This suggests that translation and/or transcription of the HO-1 and
      HSP70 genes are blocked in neurons and glia destined to die within infarcts,
      whereas translation of these stress genes continues in the endothelial cells. The
      duration of ischemia required to induce HSP70 in cortical neurons appears to be
      less than that required to induce HO-1 in cortical glia. Prolonged spreading
      depression and/or diffuse hemispheric ischemia may induce HO-1 in glia throughout
      the ipsilateral cortex via immediate early gene activation of the AP-1 site in
      the HO-1 promoter. Since HO-1 degrades heme, a pro-oxidant, to antioxidant
      molecules, the induction of HO-1 may augment oxidative defense mechanisms
      compromised by cerebral ischemia.

PMID- 8738153
TI  - Partial striatal dopamine depletion differentially affects striatal substance P
      and enkephalin messenger RNA expression.
AB  - Near total striatal dopamine denervation results in a decrease in substance P and
      an increase in enkephalin messenger RNA expression in the striatum. It is unknown
      whether partial depletions of striatal dopamine content produce similar changes
      in these peptide messenger RNAs. To test whether compensations in dopamine
      synthesis and release following partial dopamine denervation prevent the lesion
      induced alterations in substance P and enkephalin messenger RNAs, varying
      concentrations of 6-hydroxydopamine were injected unilaterally into the
      substantia nigra. Seven days after injection of 6-hydroxydopamine (2-16
      micrograms) or vehicle, in situ hybridization histochemistry was used to examine
      tyrosine hydroxylase messenger RNA in the substantia nigra and substance P and
      enkephalin messenger RNAs in the striatum. The extent of the dopamine depletion
      was determined by measuring striatal dopamine tissue content. The decrease in
      tyrosine hydroxylase messenger RNA paralleled the change in striatal tissue
      dopamine content. Substance P messenger RNA was decreased in all lesioned rats.
      In contrast, a significant increase in enkephalin messenger RNA was not detected
      until striatal dopamine was reduced to 10% of control levels. These results
      suggest that compensations within the residual dopamine system are not sufficient
      to maintain normal striatal substance P messenger RNA levels in partially
      denervated animals, but are sufficient to maintain normal striatal enkephalin
      messenger RNA expression.

PMID- 8738154
TI  - Widespread brain distribution of mRNA encoding the orphan neurotransmitter
      transporter v7-3.
AB  - Orphan transporter v7-3 is a member of a new subfamily of Na+, Cl- dependent
      neurotransmitter transporters with two large extracellular loops. Distribution of
      v7-3 mRNA was investigated in the rat brain. In situ hybridization study revealed
      that v7-3 mRNA was widely distributed in the rat central nervous system,
      including the olfactory bulb, the hypothalamus, the cerebral cortex, the
      hippocampus, and the cerebellum. In addition, intense v7-3 mRNA expression was
      found in the motor nuclei including the oculomotor nucleus, abducens nucleus,
      trigeminal motor nucleus, facial nucleus, hypoglossal nucleus and ventral horn of
      spinal cord. Intense hybridization signals were also observed in the nuclei
      containing monoaminergic neurons, such as locus coeruleus, the substantia nigra
      pars compacta, the ventral tegmental area, the dorsal raphe nucleus and the
      median raphe nucleus. This multifocal and broad nature of the v7-3 distribution
      suggests widespread roles for this gene product in neurons mediating several
      important brain function.

PMID- 8738155
TI  - Transcription factors in primary glial cultures: changes with neuronal
      interactions.
AB  - Several astrocyte gene products, such as enkephalin and glial fibrillary acidic
      protein (GFAP), are expressed at higher levels under in vitro conditions relative
      to in vivo. We have observed that cultured glial cells express high basal levels
      of transcription factors, such as fos-related antigens (Fra), c-Jun, JunD, and
      cAMP responsive element binding protein (CREB). When neuronal cells are plated on
      top of the monolayers, the expression of Fra, c-Jun, JunD, and GFAP decreases in
      the astroglial cells. The DNA binding activity to the AP-1-like sites of the GFAP
      and proenkephalin genes was examined in these cultures. The protein complex from
      glial cultures which recognizes the GFAP AP-1 element contained Fra
      immunoreactivity while the DNA binding from mixed neuronal/glial cultures
      consists of CREB-immunoreactive proteins. In glial cultures, no binding occurred
      to the proenkephalin AP-1-like element but a CREB-immunoreactive complex
      recognized this sequence in the mixed cultures. Thus, with the addition of
      neurons, both transcription factors and target gene products decrease in
      astroglial cells. The proteins that compose gene modulatory complexes also change
      suggesting that regulation of astroglial gene expression is modulated by neurons.

PMID- 8738156
TI  - Glucocorticoid interactions with ethanol effects on depolarization-induced
      calcium influx in brain synaptosomes.
AB  - Depolarization-induced Ca2+ influx in brain synaptosomes is known to be inhibited
      by ethanol and stimulated by glucocorticoids. The present study was undertaken to
      characterize the interactions of corticosterone (CORT) with ethanol effects on
      45Ca2+ uptake in synaptosomes depolarized by high K+ (70 mM). CORT was shown to
      antagonize the inhibitory effects of ethanol on the fast-phase component of the
      K(+)-induced 45Ca2+ uptake (the initial 3 s following depolarization).
      Glucocorticoid antagonism of ethanol inhibition of the 45Ca2+ uptake exhibited a
      high degree of steroid specificity; steroids with glucocorticoid activity
      including cortisol, dexamethasone and triamcinolone were effective, whereas
      gonadal steroids and excitatory neuroactive steroid metabolites were ineffective.
      From the shift of concentration-response relationships when CORT and ethanol were
      present in combination, the interaction between steroid stimulation and ethanol
      inhibition of 45Ca2+ uptake occurred in an additive manner over the range of
      their effective concentrations. Parallel to 45Ca2+ uptake, the binding sites for
      [3H]PN 200-110 were reduced by ethanol and increased by CORT. These opposite
      effects on [3H]dihydropyridine labeled sites were found also to antagonize each
      other, and the antagonism again occurred in an additive relationship. These
      results demonstrate that glucocorticoids antagonized ethanol inhibition of
      voltage-dependent Ca2+ channel activity in brain synaptosomes, and support the
      notion that these steroids may be among the endogenous factors that modulate
      neuronal sensitivity to ethanol.

PMID- 8738157
TI  - Molecular characterization and localization of human metabotropic glutamate
      receptor type 4.
AB  - Oligonucleotides of consensus sequences from rat metabotropic glutamate receptor
      (mGluR) genes were synthesized and used to amplify human DNA by the polymerase
      chain reaction (PCR). Five unique human sequences homologous to these rat
      receptor genes were isolated including mGluR4. A human cerebellum cDNA library
      was screened using this amplified mGluR4 sequence as a probe and yielded clones
      which between them contained the complete coding sequence for human mGluR4. The
      coding sequence is very similar to the equivalent rat gene (90% DNA sequence
      identity and 97% predicted protein sequence identity). The mGluR4 cDNA was
      transfected in Chinese hamster ovary (CHO) cells and stable clonal cell lines
      were isolated. Stimulation of the expressed receptor by L-2-amino-4
      phosphonobutyrate (L-AP4), L-glutamate or (1S,3R)-1-aminocyclopentane-1,3
      dicarboxylic acid (1S,3R-ACPD) resulted in a reduction of forskolin-stimulated
      cyclic AMP (cAMP) with EC50 values of 0.2, 13 and 90 microM respectively.
      Quisqualate had little effect at concentrations up to 1 mM. In Northern blots
      mGluR4 mRNA appears to be brain-specific, and shows a distinct distribution
      (excluding the cerebellum), being expressed in the thalamus, hypothalamus and
      caudate nucleus. In situ hybridization studies on human brain sections confirmed
      this general pattern of distribution. The strongest mGluR4 mRNA signal was found
      in the cerebellar granule cells consistent with the reported distribution of
      mGluR4 in the rat brain. The major difference from the rat brain is the presence
      in the human brain of mGluR4 mRNA in the caudate nucleus and putamen.

PMID- 8738158
TI  - Analysis of interaction sites in homo- and heteromeric complexes containing Bcl-2
      family members and the cellular prion protein.
AB  - The cellular prion protein (PrP) binds to the C-terminus of Bcl-2 but not Bax.
      Therefore, we examined whether the C-terminus of Bcl-2 was important for other
      homomeric and heteromeric protein-protein interactions. Using the yeast two
      hybrid system and co-immunoprecipitation, three sites of homomeric interactions
      were identified within Bcl-2. The carboxy terminal 37 amino acids selectively
      homodimerized. Two additional regions of Bcl-2 (residues 1-129 and 126-200)
      interacted with each other, but not themselves permitting both intra- and
      intermolecular association. In addition, we analyzed heteromeric interactions of
      Bcl-2 with PrP and two Bcl-2 related proteins, Bax and A1. The domain
      requirements for binding of those three proteins to Bcl-2 were different from one
      another. Bax binding required almost the entire Bcl-2 molecule, while A1 bound to
      the amino terminal region (residues 1-82). PrP associated with the carboxy
      terminus of Bcl-2 (amino acids 200-236). These data suggest configurational
      models for Bcl-2 containing complexes. First, Bcl-2 may exist as both
      heterodimers and heteromultimers. Second, molecules such as Bax and A1 may serve
      to cap chains of Bcl-2 homodimers by interacting with dimerization domains in the
      extramembrane region. PrP may disrupt chains of Bcl-2 molecules at the homomeric
      association site in the transmembrane region.

PMID- 8738159
TI  - Modulation by 5-hydroxytryptamine of the somatostatin receptor-effector system
      and somatostatin levels in rat brain.
AB  - The role of 5-hydroxytryptamine (5-HT) in the acute regulation of the rat brain
      somatostatin (SS) receptor-effector system and somatostatin-like immunoreactivity
      (SSLI) content was examined. 5-HT administered i.c.v. in a volume of 10
      microliters at a dose of 0.5 microgram (pH 3.4) increased the SSLI concentration
      at 60 min in the Wistar rat frontoparietal cortex and hippocampus (60%, P < 0.05;
      72%, P < 0.01; respectively). These changes were associated with a significant
      increase in the total number of specific SS receptors in the frontoparietal
      cortex (24%, P < 0.05) and hippocampus (20%, P < 0.05), without changes in the
      affinity constant as compared with the control group. No significant differences
      were seen in the basal and forskolin (FK)-stimulated adenylate cyclase (AC)
      activities in both brain areas of 5-HT-treated rats when compared to the control
      group. The capacity of SS to inhibit the FK-stimulated AC activity in the
      frontoparietal cortex and hippocampus of 5-HT-treated rats was lower than in the
      control groups. The ability of the stable GTP analogue 5'
      guanylylimidodiphosphate (Gpp(NH)p) to inhibit FK-stimulated AC activity in
      frontoparietal cortical and hippocampal membranes was markedly decreased in 5-HT
      treated rats. To determine if the above-mentioned changes were related to the 5
      HT activation of central 5-HT1 and 5-HT2 receptors, a non-selective 5-HT1 and 5
      HT2 receptor antagonist, methysergide, was administered 60 min before the 5-HT
      injection. Pretreatment with methysergide (5 mg/kg i.p. in a volume of 400
      microliters) prevented the 5-HT-induced changes in the SS receptor-effector
      system and in SSLI levels in both brain areas. Methysergide alone had no
      observable effect on the somatostatinergic system. These results suggest that the
      frontoparietal cortical and hippocampal somatostatinergic system can be regulated
      by 5-HT receptors.

PMID- 8738160
TI  - Structure, localization and action of a novel inhibitory neuropeptide involved in
      the feeding of Lymnaea.
AB  - A neuropeptide that strongly inhibits the spontaneous contractions of the
      oesophagus in Lymnaea has been characterized as GAPRFVamide. Direct mass
      spectrometry of nervous tissues and immunocytochemical studies show that the
      peptide is synthesized by neurones in the buccal ganglia and transported to the
      oesophagus via the dorso-buccal nerve. In accordance with the function of the
      peptide, immunoreactive fibres are detected within the muscle layer of the
      oesophagus. Finally, mass spectrometry reveals the presence of a number of
      unidentified peptides in the nerves that innervate the oesophagus, which suggests
      that oesophageal activities may be modified by multiple peptides.

PMID- 8738162
TI  - BDNF increases the expression of neuropeptide Y mRNA and promotes
      differentiation/maturation of neuropeptide Y-positive cultured cortical neurons
      from embryonic and postnatal rats.
AB  - The effects of neurotrophic factor on the expression of neuropeptide Y (NPY) mRNA
      and on morphology of NPY-immunoreactive neurons were investigated. Brain-derived
      neurotrophic factor (BDNF) increased the expression of NPY mRNA in cultured
      cortical neurons from both embryonic and postnatal rats. BDNF also increased the
      number of NPY neurons. Furthermore, multipolar neurites from NPY neurons were
      observed in cultures treated with BDNF, whereas only monopolar and bipolar
      neurites were observed in control cultures. These results suggest that BDNF not
      only increases the expression of NPY mRNA but also promotes the
      differentiation/maturation of NPY ergic neurons both in number and morphology.
      NPY expression was strongly increased by neurotrophin-4/5 similarly to BDNF and
      neurotrophin-3 evoked a slight increase. In contrast, basic fibroblast growth
      factor, cilliary neurotrophic factor and interferon-gamma had no effect on NPY
      expression.

PMID- 8738161
TI  - Up-regulation of cystatin C by microglia in the rat facial nucleus following
      axotomy.
AB  - Cystatin C, a cysteine proteinase inhibitor, is expressed in the central nervous
      system (CNS) as well as many other organs of mammals. However, little is known
      concerning whether its expression is regulated under pathological conditions of
      the CNS and what types of cells are responsible for this regulation. We performed
      differential hybridization screening of cDNA libraries derived from the rat
      facial nucleus and found a cDNA of rat cystatin C to be up-regulated following
      facial nerve axotomy. In situ hybridization using an RNA probe for rat cystatin C
      revealed that cystatin C mRNA in the facial nucleus was markedly increased in
      amount by day 7 after axotomy and was then decreased to the normal level by day
      50. The intense signal for cystatin C mRNA in the damaged facial nucleus was
      localized in the glial cells which had the morphological characteristics of
      microglia. Light and electron microscopic immunohistochemistry using a rabbit
      antibody specific for cystatin C confirmed that microglia in the damaged facial
      nucleus were strongly positive for cystatin C. The immunoreactivity was also
      found in the extracellular space, consistent with the fact that cells producing
      cystatin C generally secrete this protein. These results demonstrate that
      cystatin C is markedly up-regulated by microglia in response to axotomy and is
      probably secreted by these cells into the extracellular space, suggesting that
      this proteinase inhibitor has (a) significant function(s) in the processes of
      neuronal degeneration, regeneration, and/or repair subsequent to axotomy.

PMID- 8738163
TI  - The endogenous benzodiazepine receptor ligand ODN increases cytosolic calcium in
      cultured rat astrocytes.
AB  - We have investigated the production of diazepam-binding inhibitor (DBI)-related
      peptides by astrocytes in primary culture and we have determined the effect of
      the octadecaneuropeptide DBI[33-50] (ODN) on the intracellular calcium
      concentration ([Ca2+]i) in astrocytes. Immunocytochemical labeling with
      antibodies against ODN showed that cultured astrocytes retain their ability to
      synthesize DBI in vitro. Cultured astrocytes were also found to release
      substantial amounts of ODN-immunoreactive material, and a brief exposure of
      astrocytes to a depolarizing potassium concentration resulted in a 5-fold
      increase in the rate of release of the ODN-like peptide. Microfluorimetric
      measurement of [Ca2+]i with the fluorescent probe indo-1 showed that nanomolar
      concentrations of ODN induced a marked increase in [Ca2+]i. The stimulatory
      effect of ODN on [Ca2+]i was not affected by calcium channel blockers or by
      incubation in Ca(2+)-free medium. In contrast, thapsigargin, an inhibitor of
      microsomal Ca(2+)-ATPase activity, totally abolished the ODN-induced increase in
      [Ca2+]i. Repeated pulses of ODN caused attenuation of the response, indicating
      the existence of a desensitization phenomenon. Preincubation of astrocytes with
      pertussis toxin totally blocked the effect of ODN on [Ca2+]i. The present study
      indicates that ODN-related peptides are synthesized and released by glial cells.
      Our results also show that synthetic ODN induces calcium mobilization from an
      intracellular store through stimulation of pertussis toxin-sensitive G protein.
      Taken together, these data suggest that endozepines act as paracrine and/or
      autocrine factors controlling the activity of astroglial cells.

PMID- 8738164
TI  - Rat C6 and human astrocytic tumor cells express a neuronal type of glutamate
      transporter.
AB  - C6 glioma cells take up aspartate and glutamate by a Na(+)-dependent transporter.
      Using the polymerase chain reaction and degenerate oligonucleotide primers
      corresponding to conserved regions of previously cloned glutamate transporters,
      we isolated from these cells a partial cDNA clone with a sequence of the neuronal
      type EAAC1 glutamate transporter. The cells express a 4.4 kb message that
      hybridizes to this cDNA, and they do not express either of the previously
      described glial type glutamate transporters, GLT-1 or GLAST. The cells were
      sensitive to the toxic aspartate analog alanosine, which enters the cells by a
      glutamate transporter. Several human brain tumors examined, including some
      astrocytic tumors, expressed the EAAT3 glutamate transporter, which is the human
      homolog of the rodent EAAC1 transporter. Some of the tumors also expressed the
      other types of glutamate transporter.

PMID- 8738165
TI  - Kainate, GABAA and NMDA receptors in Xenopus oocytes expressing mRNA from the
      cortex of mice kindled with FG 7142.
AB  - The repeated administration of the beta-carboline, FG 7142, to mice leads to
      'chemical kindling', i.e., the development of seizures following doses which were
      initially insufficient to produce convulsive activity. Messenger RNA (mRNA) was
      prepared from the cortex of control and FG 7142-treated mice killed at 10-12 days
      or at 28-45 days after the last kindling injection, and this mRNA was injected
      into Xenopus oocytes. At 3-4 days following injection, a voltage clamp technique
      was used to record responses to kainic acid, gamma-aminobutyric acid (GABA), and
      N-methyl-D-aspartate (NMDA). Kainate was significantly more potent in oocytes
      expressing mRNA from kindled mice killed at either 10-12 or 28-45 days than in
      those injected with control mRNA. GABA also was more potent in oocytes with mRNA
      from kindled mice killed at 10-12 days, but this difference was not present at
      the longer interval. Chemical kindling did not change the response to NMDA. The
      current-voltage relation for kainate responses was linear, and plots from kindled
      and control mRNA were similar. The persistent increase in potency of kainate, an
      excitatory glutamate ligand, may play a role in producing the lowered FG 7142
      threshold characteristic of kindled mice.

PMID- 8738166
TI  - Neuronal and glial localization of two GABA transporters (GAT1 and GAT3) in the
      rat cerebellum.
AB  - The localization of GABA transporters (GAT1 and GAT3) was examined
      immunocytochemically in the rat cerebellum at both light and electron microscopic
      levels using antibodies specific for each subtype. Immunoblot analysis showed
      that the antibodies against GAT1 and GAT3 specifically recognized their
      respective antigens in the cerebellum. Both GAT1 and GAT3 were found in the
      neuropil but not in neuronal somata or glial cell bodies. GAT1 immunoreactivity
      was seen throughout all layers of the cerebellar cortex with the highest
      immunoreactivity in the molecular layer, but little immunoreactivity was found in
      the deep cerebellar nuclei. GAT1 immunoreactivity was seen in the pinceau area of
      the Purkinje cell layer and in the mossy fiber glomeruli in addition to the
      neuropil of the molecular layer. Weak GAT3 immunoreactivity was found in the
      granular layer of the cerebellar cortex, and intense immunoreactivity was
      observed around the unstained large neurons in the deep cerebellar nuclei.
      Electron microscopic analysis of the cerebellum revealed that GAT1
      immunoreactivity was predominantly localized in the presynaptic terminals, while
      GAT3 immunoreactivity was localized in the glial processes. These results
      suggested that GABAergic transmission at synapses is terminated by three GABA
      uptake systems, (1) only neuronal uptake through GAT1, (2) only glial uptake
      through GAT3, and (3) both neuronal and glial uptake through GAT1 and GAT3
      respectively, and also that the GABA uptake system is different in each type of
      GABAergic neuron.

PMID- 8738167
TI  - Co-expression of two gene products in the CNS using double-cassette defective
      herpes simplex virus vectors.
AB  - Defective herpes simplex virus (HSV) vectors are an efficient means to deliver
      genes to cells of the central nervous system (CNS). Such vectors containing two
      independent transcription units would be extremely valuable for many studies,
      including the comparative analysis of promoter function and expression of
      multiple gene products in the CNS. We have constructed a 'double-cassette' vector
      expressing two easily detectable marker enzymes, beta-galactosidase (beta-gal)
      and human placental alkaline phosphatase (AP). Cells infected in vitro, including
      neurons and glia, and in vivo expressed both gene products.

PMID- 8738168
TI  - Glucocorticoid upregulation of glutamate dehydrogenase gene expression in vitro
      in astrocytes.
AB  - Glutamate, the major excitatory neurotransmitter, is preferentially catabolized
      in astrocytes by glutamate dehydrogenase (GDH). Treatment of an astrocytic cell
      line with hydrocortisone (10(-5) M) resulted in increased expression of GDH mRNA.
      Transfection of the cells with truncated parts of the GDH promoter showed that
      genomic responsive elements activated by hydrocortisone are localized in the 
      557/+1 region of the promoter. This control of GDH expression by glucocorticoids
      may be involved in their protective effect against glutamate excitotoxicity.

PMID- 8738169
TI  - Enhanced gene expression for phosphatidylinositol 3-kinase in the hypoglossal
      motoneurons following axonal crush.
AB  - We attempted to see whether or not gene expression of phosphatidylinositol 3
      kinase (PI 3-kinase) is changeable in the hypoglossal nucleus of rats after
      hypoglossal nerve crushing by in situ hybridization histochemistry. After
      unilateral nerve crushing, an apparent enhancement of gene expression for PI 3
      kinase was observed in individual neurons of the hypoglossal nucleus at the
      operated side on the first postoperative day, and it was sustained for 7
      postoperative days. Thereafter the expression decreased at the operated side and
      no significant difference in the expression level was noticed between the
      operated nucleus and the contralateral, non-operated or sham-operated nucleus on
      postoperative day 14. The present study suggests that PI 3-kinase contributes to
      some important roles in morphological changes of mature neurons associated with
      nerve regeneration.

PMID- 8738170
TI  - Analysis of sequence and pathogenic properties of two variants of
      encephalomyocarditis virus differing in a single amino acid in VP1.
AB  - The encephalomyocarditis (EMC) virus-induced diabetes-like syndrome in mouse
      inbred strains was used as a model to study the insulin-dependent diabetes
      mellitus (IDDM). Our investigations were performed with two EMC virus variants,
      PV2 and PV7. After infection of SJL mice with 10(5) PFU of PV2 about 70% of the
      animals developed a diabetes-like syndrome, whereas the PV7 infected mice
      appeared healthy. Histological examination and in situ experiments revealed that
      the islets of Langerhans are a main target of PV2, whereas PV7 infection leads to
      only modest changes of the islets. Sequence analysis of both variants revealed
      one amino acid exchange within the capsid protein VP1. Hence, we describe the
      first diabetogenic and non-diabetogenic EMCV variants differing in only one
      single amino acid.

PMID- 8738171
TI  - A variable region of Anticarsia gemmatalis nuclear polyhedrosis virus contains
      tandemly repeated DNA sequences.
AB  - A variable region (PstI-T fragment) of two genotypic variants of the Anticarsia
      gemmatalis multiple nucleocapsid nuclear polyhedrosis virus (AgMNPV) was
      sequenced and compared. This region, which is known to have deletions and
      duplications in AgMNPV variants, was shown to be formed of units of a 127 bp
      tandemly repeated sequence containing two 30 bp imperfect palindromes. Southern
      blot experiments showed that the PstI-T fragment contained one of the four
      homologous regions mapped interspersed in the AgMNPV genome. The comparison of
      the nucleotide sequences of the two variants, AgMNPV-2D and AgMNPV-D7, showed
      that the difference between these two variants in one of these regions (hr4) was
      caused by the addition or elimination of 381 bp corresponding exactly to three of
      the 127 bp repeated sequences. An analysis of the sequence showed homology to the
      homologous regions (hr) of other baculoviruses. The sequence upstream of the
      repetitive region contained a sequence homologous to the N-terminal portion of
      the Autographa californica MNPV and Choristoneura fumiferana MNPV p74 gene.

PMID- 8738172
TI  - Molecular characterization of carrier rabies isolates.
AB  - We compared the genomes of nine dog rabies virus isolates using two molecular
      methods. The viruses used in the comparison included three Ethiopian rabies
      strains from carrier dogs, a street strain from a rabid dog from the same
      geographic area, two saliva isolates made from an experimentally infected carrier
      dog, the virus isolated from the tonsil of this carrier dog at necropsy, and two
      laboratory strains. We produced overlapping polymerase chain reaction (PCR)
      segments spanning 97% of the genome. Restriction analysis of these PCR products
      with AvaII, Bcll, and BamHI detected 39 variable sites representing 668
      nucleotides (nt) or 5.5% of the genome. We also compared the DNA and the deduced
      peptide sequences of a 200-nt segment of the 3' end of the rabies nucleoprotein
      gene. Previous work with these Ethiopian carrier viruses and the endemic street
      strain had failed to show any differences among them. Both restriction mapping
      and sequence analysis of 200 nt of the nucleoprotein gene allowed us to
      individually identify these isolates. Phylogenetic analyses of these data sets
      showed only the two saliva isolates of the experimentally infected carrier dog to
      be identical. Each of the viruses in this study, including the one isolated from
      the tonsil of the experimentally infected carrier dog, could be distinguished by
      these techniques.

PMID- 8738173
TI  - Site-directed mutagenesis of the double-stranded RNA binding domain of
      bacterially-expressed sigma 3 reovirus protein.
AB  - The affinity of the reovirus sigma 3 protein for double-stranded RNA (dsRNA) is
      well established, and efforts have been made to identify the amino acids involved
      in this property. In the present study, we further examined the importance of two
      basic amino acids motifs, located in the carboxy-terminal third of the protein.
      Mutants, previously characterized in COS cells, were expressed in bacterial cells
      using the pET expression system. The capability of the different mutants to
      interact with dsRNA was then determined by the binding of radiolabeled dsRNA to
      proteins resolved by SDS-polyacrylamide gel electrophoresis and transferred to
      nitrocellulose filters. It appears that the most carboxy-terminal motif is
      absolutely required for the binding but the second motif also contributes to this
      property. However, only the carboxy-terminal motif is required for normal binding
      upon removal of the amino-terminal domain of the protein by proteolytic cleavage,
      a procedure previously shown to increase dsRNA-binding. The basic charges in both
      motifs are important, while breaking of their potential to adopt an alpha helical
      configuration does not affect binding efficiency. Furthermore, alanine
      substitution of a single basic amino acid in the carboxy-terminal motif can be
      sufficient to strongly reduce the binding of dsRNA to the protein. Altogether,
      these data suggest that basic amino acids of the sigma 3 carboxy-terminal motif
      are directly involved in dsRNA binding, while the other basic motif may
      contribute by preventing an inhibitory effect of the amino-terminal portion of
      the protein.

PMID- 8738174
TI  - Regulation of transplacental virus infection by developmental and immunological
      factors: studies with lactate dehydrogenase-elevating virus.
AB  - Placental and fetal infections with lactate dehydrogenase-elevating virus (LDV)
      were determined by virus titration, indirect fluorescence antibody (IFA), and in
      situ hybridization with cDNA probes. Experiments were designed to determine the
      effects of gestational age, timing of maternal LDV infection, and immunological
      (antibody and cytokine) factors on mouse placental and fetal LDV infection. Virus
      infection of the placenta was detected at high levels (almost all placentas
      infected) within 24 h post-maternal infection (p.m.i.), whereas fetal LDV
      infection was detected only at a low level by 24 h p.m.i. The percentage of
      fetuses becoming LDV infected progressively increased between 24 and 72 h p.m.i.
      When fetal infection was studied at 72 h p.m.i., earlier gestational ages (9-11
      days) were associated with fetal resistance to infection, whereas between 12.5
      and 15 days of gestation, virus infection was detected in 50-71% of fetuses.
      Maternal treatment with interferon-gamma (IFN-gamma) or anti-LDV monoclonal
      antibodies was associated with reduced rates of fetal, but not placental, LDV
      infection. These results demonstrate that both developmental and immunological
      factors are important in the regulation of transplacental LDV infection.

PMID- 8738175
TI  - Rabbit hemorrhagic disease virus (RHDV): ultrastructure and biochemical studies
      of typical and core-like particles present in liver homogenates.
AB  - Calicivirus particles isolated from rabbits suffering from acute RHD were
      compared with virions found in rabbits with chronic disease. Liver homogenates of
      rabbits with the protracted disease display no hemagglutinating activity and
      contain viral particles with diameters of 25-27 nm. These virions contain only
      one structural protein of 30 kDa and are distinctly smaller than intact rabbit
      hemorrhagic disease virus (RHDV) (32-40 nm). To prove the RHDV identity of the
      smaller virions, their reactivity with RHDV specific antibodies was investigated
      by immunoblots of the virion protein and by immunoelectron microscopy.
      Proteolytic digestion of RHDV particles with alpha-chymotrypsin did not transform
      RHDV into the smaller form. We assume that these core-like particles (CLPs) are
      not a result of proteolytic digestion but arise from a truncated RHDV genome or
      defective expression.

PMID- 8738176
TI  - Molecular cloning and nucleotide sequence determination of three envelope genes
      of classical swine fever virus Taiwan isolate p97.
AB  - A strain of classical swine fever virus (CSFV) has been isolated in Taiwan. The
      cDNA coding for three envelope glycoproteins E1, E2 and E3 were molecularly
      cloned from purified viral particles using the reverse transcription-polymerase
      chain reaction (RT-PCR) method and sequence-specific primers. The resulting PCR
      products (1113 bp for E1. 699 bp for E2 and 567 bp for E3) were cloned into the
      SmaI site of pUC19 and then subjected to DNA sequence analysis. Data showed that
      nucleotide sequence of the three envelope genes shared a 82-83% homology with the
      corresponding genes of three other strains (Alfort, Brescia and Weybridge).
      However, the homology of the deduced amino acid sequence was greater than 90%
      among the four strains. The potential asparagine-linked glycosylation sites for
      E1 (5 sites), E2 (7 sites) and E3 (2 sites) were conserved. This suggests that
      the Taiwan p97 strain is distinct from other three strains described. The
      variations may have implications for future vaccine development. The sequence has
      been submitted to GenBank. The accession numbers are U43924 and U03290.

PMID- 8738177
TI  - Sequence analysis of wheat and oat furovirus capsid protein genes suggests that
      oat golden stripe virus is a strain of soil-borne wheat mosaic virus.
AB  - In northern blots, cDNA probes prepared to soil-borne wheat mosaic virus (SBWMV)
      RNA-1 and RNA-2 hybridized to RNA-1 and RNA-2, respectively, from a UK isolate of
      oat golden stripe virus (OGSV), as well as to their homologous RNAs. RT-PCR was
      used to amplify, clone and sequence a region of about 750 nucleotides spanning
      the capsid protein gene and part of the readthrough protein on RNA-2 from OGSV, a
      French isolate of SBWMV and two stable deletion mutants (Lab1 and Okl-7) of SBWMV
      isolates from Nebraska and Oklahoma respectively. There was very high (96.7
      99.1%) nucleotide homology between all these sequences and the wild-type SBWMV
      sequences from Nebraska and Oklahoma. OGSV was more similar to SBWMV from France
      and Nebraska than were any of the isolates to SBWMV from Oklahoma. Of the few
      differences in the deduced amino acid sequences of the capsid proteins from the
      different isolates, OGSV differed from all SBWMV isolates only in one amino acid
      (isoleucine for valine at position 88). The high degree of similarity suggests
      that OGSV may best be classified as an oat strain of SBWMV.

PMID- 8738178
TI  - Sequence of the nucleocapsid protein gene of subgroup A and B avian
      pneumoviruses.
AB  - The nucleocapsid protein (N) gene of two subgroup A and one subgroup B strains of
      avian pneumovirus has been cloned and sequenced. The gene of all three isolates
      comprised 1197 nucleotides (nt), which formed a single major open reading frame,
      potentially encoding a protein of 391 amino acid residues. The N gene of the two
      subgroup A isolates differed by only 1 nt but differed by 282 (24%) nt and 35
      (11%) amino acids from the B isolate. The predicted protein was identical in
      length to that of human, bovine and ovine respiratory syncytial viruses, the
      amino acid identity being approximately 41% overall but with some regions of
      identity > 90%.

PMID- 8738179
TI  - Prokaryotic expression of an immediate-early gene of human herpesvirus 6 and
      analysis of its viral antigen expression in human cells.
AB  - Segments of an immediate-early (1E) protein (1E03; 958 amino acids (aa)), encoded
      by clone pSTY03, of human herpesvirus 6 (HHV-6) variant B strain HST were
      expressed as beta-galactosidase fusion proteins in Escherichia coli. Using
      Western blot analysis, and the serum of a patient having high titer anti-HHV-6
      antibodies, an antigenic region of the IE03 protein was mapped between residues
      340 and 505 (pUE03IE-M). The fusion protein expressed in E. coli harboring
      plasmid pUE03IE-M was purified after electrophoresis in SDS-PAGE, and then
      immunized in mice to obtain a monospecific antibody. Monospecific antibody raised
      against the fusion protein reacted with IE03 protein species with apparent
      molecular weights of 155 and 170 kDa, and was detected as granular fluorescence
      in nuclei of infected cells by an immunofluorescence antibody test. Furthermore,
      this antibody reacted only with HHV-6 variant B, but did not react with HHV-6
      variant A. The IE03 protein was confirmed to be an IE protein, since the
      synthesis of this protein was observed in infected cells that were first treated
      with cycloheximide, which was then replaced with actinomycin D. Further, it was
      also detected as early as 4 h after infection.

PMID- 8738180
TI  - Regulatory properties of the integrated long terminal repeat of the feline
      immunodeficiency virus.
AB  - To examine the regulatory properties of feline immunodeficiency virus (FIV) long
      terminal repeat (LTR) integrated into host chromatin, Crandell feline kidney
      cells were stably transfected with the FIV LTR that directs the bacterial
      chloramphenicol acetyltransferase (CAT) gene. Using these cells, we examined the
      effects of treatment with several chemical agents, infection with feline viruses,
      or transfection with effector plasmids expressing FIV gene products on FIV LTR
      directed gene expression. Among them, treatment with the phorbol ester (a strong
      activator of protein kinase C), forskolin (an inducer of cyclic-AMP), 5
      azacytidine (a DNA methylation antagonist), or infection with feline herpesvirus
      type 1 (FHV-1), resulted in induction of CAT activity in the cells. These results
      suggest that the integrated FIV LTR is stimulated by cellular transcriptional
      factors induced by phorbol ester, forskolin and FHV-1, and is also inactivated by
      DNA methylation. Furthermore, this permanent cell line can be used as a screening
      system of activators of the FIV LTR.

PMID- 8738181
TI  - Validation of assay of catechol-O-methyltransferase activity in human
      erythrocytes.
AB  - The multistep assay of specific catechol-O-methyltransferase (COMT) activity in
      human erythrocytes was validated. Enzyme preparations from lysed erythrocytes
      were incubated with a substrate (3,4-dihydroxybenzoic acid) in the presence of
      Mg2+ and S-adenosylmethionine. The reaction products (vanillic acid and
      isovanillic acid) were analyzable by HPLC with electrochemical detection directly
      in the incubation medium after protein precipitation. The precision was
      calculated in order to define the random variability associated with the method
      by intra-assay and inter-assay relative standard deviations (RSDs) for the assays
      of both reaction products and protein. The intra-assay RDSs for the specific
      activities were between 4.8 and 11.9% (n = 5-6) at two levels of COMT activity.
      The inter-assay RSDs were between 6.4 and 14.2% (n = 5-6), respectively. The
      total variation was mostly caused by the protein assay and the HPLC assay, and
      contributions from the sample preparation and incubation steps were minor. Some
      results from the clinical application of the erythrocyte COMT assay are also
      reported. For both normal volunteers and patients having Parkinson's disease, a
      single 400 mg dose of entacapone, a peripherally acting COMT inhibitor, decreased
      the erythrocyte COMT activity. The application demonstrates that the assay was
      able to detect differences between the subjects and the effect of COMT inhibition
      in the clinical study.

PMID- 8738182
TI  - Half-fraction and full factorial designs versus central composite design for
      retention modelling in reversed-phase ion-pair liquid chromatography.
AB  - In a previous paper (J. O. De Beer, C. V. Vandenbroucke and D. L. Massart, J.
      Pharm. Biomed. Anal., 12, (1994) 1379-1396) liquid chromatographic (LC) retention
      modelling of the cough-syrup compounds methyl para-hydroxybenzoate (MPHB) and
      propyl para-hydroxybenzoate (PPHB), phenylephrine hydrochloride (PE) and
      chlorphenamine maleate (CPM) was studied using a face-centred central composite
      design. It is examined whether smaller half-fractional and full factorial designs
      with fewer experiments tend to reliably predict retention times of the latter
      compounds as well. Simplified regression modelling, however, neglecting more
      first-order and interactive effects and disregarding pure second-order effects,
      has to be set up. These smaller designs finally satisfy the prediction of the
      retention of MPHB, PPHB and PE also. Retention prediction of CPM is much less
      accurate. CPM has a pKa value of 4.0, which is encompassed by the examined mobile
      phase pH limits 3.0 and 5.0. Since the largest retention shifts occur near the
      pKa value, retention prediction in this area becomes more complex. CPM retention
      modelling from a full factorial design is useful if the mobile phase pH is fixed
      at 5.0 for methanol as well as for acetonitrile as organic modifers. The full
      factorial design, applied with acetonitrile as organic modifer, enables the
      selection of suitable LC parameter combinations for fast and complete separation
      of the four compounds in cough-syrup analysis.

PMID- 8738183
TI  - Determination of diethylcarbamazine, an antifilarial drug, in human urine by 1H
      NMR spectroscopy.
AB  - 1H-NMR spectroscopy is a convenient method for determination of
      diethylcarbamazine (DEC) in urine, and can be used to monitor medication with the
      drug. Urine samples were mixed with 10% of deuterium oxide as a spectrometer
      field frequency lock, which is the only sample pretreatment required. Tailored
      excitation with the 1331 pulse was used for water peak suppression. The
      quantification of DEC was carried out with the triplet of the N-ethyl group, for
      which the T1 relaxation time was 1 s. In aqueous solutions, amounts below 1
      microgram ml-1 of DEC could be easily detected. In urine, the detectability
      depended on the level of chemical noise but was better than 10 micrograms ml-1.
      The accuracy and precision of the method were better than 15%. Analysis of urine
      from volunteers receiving a single therapeutic dose of DEC (6 mg kg-1 body weight
      orally) showed that the drug was eliminated in unchanged form during 2 days, in
      agreement with earlier results. The concentration of DEC in urine several hours
      after the intake exceeded 100 micrograms ml-1 making the 1H-NMR assay rapid and
      easy. No significant amounts of the N-oxide of DEC could be detected.

PMID- 8738184
TI  - Automated system for the on-line monitoring of powder blending processes using
      near-infrared spectroscopy. Part I. System development and control.
AB  - An automated system for the on-line monitoring of powder blending processes is
      described. The system employs near-infrared (NIR) spectroscopy using fibre-optics
      and a graphical user interface (GUI) developed in the LabVIEW environment. The
      complete supervisory control and data analysis (SCADA) software controls blender
      and spectrophotometer operation and performs statistical spectral data analysis
      in real time. A data analysis routine using standard deviation is described to
      demonstrate an approach to the real-time determination of blend homogeneity.

PMID- 8738185
TI  - Spectrophotometric and spectrofluorimetric estimation of ciprofloxacin and
      norfloxacin by ternary complex formation with eosin and palladium(II).
AB  - Spectrophotometric and spectrofluorimetric methods for the determination of two
      broad-spectrum fluoroquinolone antibacterials (ciprofloxacin and norfloxacin),
      either in pure form or in tablets, are described. Both methods are based on the
      formation of a ternary complex between palladium(II), eosin and the
      fluoroquinolone in the presence of methyl cellulose, as surfactant.
      Spectrophotometrically, under the optimum conditions, the ternary complexes
      showed an absorption maximum at 545 nm, with apparent molar absorptivities of 3.4
      x 10(4) and 2.7 x 10(4) 1 mol-1 cm-1 and Sandell's sensitivities of 1.01 x 10(-2)
      and 1.12 x 10(-2) micrograms cm-2 for ciprofloxacin and norfloxacin,
      respectively. The solution of the ternary complex obeyed Beer's law in the
      concentration range 3-10 micrograms ml-1 for both quinolones. The proposed method
      was applied to the determination of the two drugs in pharmaceutical tablets. A
      fluorescence quenching method for the determination of both quinolones by forming
      this ternary complex was also investigated for the purpose of enhancing the
      sensitivity of the determination. The results obtained by the application of both
      procedures and the USP XXIII methods were in good agreement and statistical
      comparison by means of Student's t-test and the variance ratio F-test showed no
      significant differences between the three methods.

PMID- 8738186
TI  - Flow-injection spectrophotometric determination of adrenaline and dopamine with
      sodium hydroxide.
AB  - A new, rapid and economical flow-injection method for determining adrenaline and
      dopamine is proposed on the basis of the hydrolysis of these compounds in
      alkaline medium. The method was optimized by using a spectrophotometer operating
      at lambda = 390 nm as detector. Calibration graphs were linear up to 2 x 10(-4) M
      with quantification limits of 2.5 x 10(-6) M and 3.3 x 10(-6) M for dopamine and
      adrenaline respectively. Flow-injection allows the measurement of 130 samples per
      hour. The method was successfully applied for the determination of catecholamines
      in pharmaceuticals.

PMID- 8738187
TI  - Colorimetric determination of astemizole in bulk and in its pharmaceutical dosage
      forms using flow injection.
AB  - A continuous flow spectrophotometric method for determining 0.5-100 micrograms ml
      1 of astemizole in pure and in dosage forms is suggested. It depends on forming a
      pinkish orange product which can be quantified spectrophotometrically at 495 nm.
      The coloured product was due to the action of N-bromosuccinimide on astemizole in
      alkaline medium and in the presence of a cetyltrimethylammonium bromide micellar
      medium. The procedure is automated and solutions can be analysed at a rate of 167
      h-1 with a relative error of about 1.25%. The limit of detection is 0.5 microgram
      ml-1 (approximately 1.09 x 10(-6) M). The method is evaluated by a recovery study
      and by the analysis of commercial formulations.

PMID- 8738188
TI  - Protein binding of methohexital. Study of parameters and modulating factors using
      the equilibrium dialysis technique.
AB  - This paper describes the parameters that characterize methohexital-albumin
      binding and the influence of physiological or analytical factors on this binding.
      Two useful and reproducible methods for measuring the free concentration
      equilibrium dialysis (ED) and ultrafiltration (UF)-are described and their
      performances are compared. Methohexital binds exclusively to albumin according to
      a two-class binding model. The first is a saturable class site of high affinity
      constant (KA = 11 200 M-1) and a number of sites per albumin molecule of 1. The
      second is a non-saturable site of poorer affinity (nKA = 810 M-1). The bound
      fraction of methohexital in the therapeutic range and at physiological albumin
      concentration is 86.7 +/- 0.9% in isolated albumin solution. In serum, it ranges
      from 80 to 84.5%, according to subjects (n = 6). Binding is inhibited by the
      presence of endogenous compounds of serum (for a given albumin concentration the
      bound fraction decreases from 90.3% in isolated albumin solution to 82.6% in
      serum), probably by free fatty acids. An increase in the bound fraction is
      observed when the pH is increased from 7 to 9. This phenomenon may be explained
      by a higher affinity of the drug towards the basic (B-form) conformation of the
      albumin molecule, in analogy with the close barbiturate thiopental. A decrease in
      the bound fraction against temperature is shown, as though binding forces
      diminished with increase in temperature. Indeed, the binding modification is less
      pronounced in the presence of serum endogenous compounds. As expected, there is
      no evidence of any effect of heparin anticoagulant on the bound fraction.
      Methohexital binding is strongly modified by the albumin concentration; the bound
      fractions change from 67 to 91% in the albumin range 150-900 microM.

PMID- 8738189
TI  - A radioimmunoassay combined with solid-phase extraction for the determination of
      a novel anti-obesity agent, ARL 15849XX, in dog plasma.
AB  - A radioimmunoassay has been developed for the determination of ARL 15849XX, a
      cholecystokinin-8 (CCK-8) analogue, in dog plasma. The method incorporates solid
      phase sample extraction and is suitable for the determination of the analyte at
      picogram per millilitre concentrations. The antiserum was raised in Suffolk-cross
      sheep following primary and booster immunisations with an immunogen prepared by
      conjugating ARL 16935XX, an analogue of ARL 15849KF, to bovine serum albumin. The
      radioligand was prepared by the no-carrier-added 125I iodination of a non
      sulphated derivative, ARL 15745XX. The solid-phase extraction procedure, carried
      out using ion-exchange aminopropyl and octadecyl sorbents sequentially, was
      introduced to remove matrix interferences in the plasma and to enhance the method
      sensitivity. The calibration range is 20-1000 pg ml-1, using a 1 ml sample of
      undiluted dog plasma.

PMID- 8738190
TI  - High-performance liquid chromatographic mapping of the oligosaccharides released
      from the humanised immunoglobulin, CAMPATH 1H.
AB  - A sensitive and reproducible method for the routine mapping of oligosaccharides
      in a humanised immunoglobulin (IgG) is described. The method involves the enzymic
      release of intact glycans using the endoglycosidase glycopeptidase-F, and
      subsequent derivatisation with 1-phenyl-3-methyl-5-pyrazolone to facilitate
      analysis by high-performance liquid chromatography (HPLC). The heterogeneous
      oligosaccharide chains are separated by a phosphate buffer-acetonitrile gradient
      reversed-phase HPLC method and monitored by ultraviolet detection at 245 nm,
      allowing the detection of picomole amounts. A number of standard oligosaccharides
      are similarly derivatised to enable classification of the types of structures
      present from a comparison of retention times.

PMID- 8738191
TI  - Analysis and pharmacokinetics of olanzapine (LY170053) and two metabolites in rat
      plasma using reversed-phase HPLC with electrochemical detection.
AB  - A sensitive HPLC assay for measurement of the antipsychotic drug, olanzapine, in
      plasma has been developed. The assay has a limit of quantitation of 1 ng ml-1 in
      plasma and utilizes solid-phase extraction and electrochemical detection. The
      method provides a linear response for olanzapine over a concentration range of 1
      100 ng ml-1 with coefficients of determination greater than 0.9912. The inter
      assay precision was 15.9% at the limit of detection and ranged from 7.33% to
      8.47% over the range of 5-100 ng ml-1. The intra-assay precision was in the range
      0.97%-26.0%. The inter-assay accuracy ranged from 98.9 to 118% and the intra
      assay accuracy ranged from 92.5% to 125% of the theoretical value. In addition,
      the assay was extended to measure the plasma levels of two metabolites of
      olanzapine, namely the N-desmethyl- and the 2-hydroxymethyl analogs. The utility
      of the assay was demonstrated following the administration of a single oral dose
      of 14C-olanzapine to rats where, at several time-points after dosing, the plasma
      was assayed for total radioactivity, levels of olanzapine, and the two
      metabolites. Olanzapine and two of its metabolites accounted for less than 50% of
      the total plasma radiocarbon; olanzapine accounting for approximately 39% at the
      Cmax, N-desmethyl for 5% and 2-hydroxymethyl for 8% respectively. The plasma
      elimination half-times for olanzapine and the two metabolites were approximately
      the same, ranging from 3.3 to 4.4 h.

PMID- 8738192
TI  - Determination of apovincaminic acid in human plasma by high-performance liquid
      chromatography.
AB  - An isocratic high-performance liquid chromatographic method is described for the
      quantitative analysis of low concentrations of apovincaminic acid (AVA) in blood
      plasma. AVA, interfering plasma components and primidone (used as the internal
      standard) were separated on a reversed-phase column of LiChrospher 60 RP-Select B
      (125 mm x 3 mm i.d.; 5 microns) (Merck). A UV-Vis detector was used at a
      wavelength of 254 nm. Each chromatographic separation was completed in 14 min and
      the results showed a relative recovery which varied between 95.9 and 116%, a good
      overall precision (relative standard deviation, 7.00%) and sensitivity over a
      linear range of 5.00-300 ng ml-1 (R = 0.999) for AVA in plasma. The method was
      applied to the analysis of plasma samples obtained from healthy subjects treated
      with one single oral dose of 20 mg of vinpocetine. The results indicate the
      method to be suitable for pharmacokinetic studies.

PMID- 8738193
TI  - High-performance liquid chromatographic determination of phenylephrine and its
      conjugates in human plasma using solid-phase extraction and electrochemical
      detection.
AB  - An HPLC method for the determination of phenylephrine and its conjugates in human
      plasma was developed and validated. The method for quantitation involved
      extraction of diluted plasma (subject to hydrolysis with beta-glucuronidase for
      30 min with 500 units of enzyme per 0.1 ml of plasma at 37 degrees C for the
      conjugates) on solid-phase weak cation-exchange cartridges followed by elution of
      the analyte and the internal standard (ethylnorphenylephrine) with 5%
      triethylamine in methanol. Analysis was carried out on a 15 cm ODS stationary
      phase using ion-pair reversed-phase chromatography. An electrochemical detector
      operated at + 1.15 V vs. Ag/AgCl was employed for detection. The standard curves
      were linear in the range 1.0-50.0 ng ml-1 for phenylephrine and 25.0-500.0 ng ml
      1 for phenylephrine obtained from its conjugates. The limit of quantitation was
      2.0 ng ml-1 (RSD = 17%) and 25.0 ng ml-1 (RSD = 18%), respectively. Acceptable
      accuracy and precision were obtained during intra- and inter-batch analyses for
      both the assays.

PMID- 8738194
TI  - Evaluation of liquid chromatography methods for the separation of ampicillin and
      its related substances.
AB  - Two laboratories collaborated to examine the selectivity of four isocratic liquid
      chromatography (LC) methods for the separation of ampicillin and its related
      substances. The United States Pharmacopeia (USP) assay method gave the best
      selectivity. Similar selectivity was obtained on C18 columns as well as on C8 and
      poly(styrene-divinylbenzene) copolymer columns. A resolution test using cefradine
      was proposed to replace the test with caffeine prescribed by the USP. Based on
      the USP method, a gradient LC method was developed for the analysis of related
      substances in ampicillin. This LC method has been proposed for assay and purity
      control in the ampicillin monographs of the European Pharmacopeia.

PMID- 8738195
TI  - High-pressure liquid chromatographic methods for ciprofloxacin hydrochloride and
      related compounds in raw materials.
AB  - High-pressure liquid chromatographic (HPLC) methods were developed for the
      analysis of ciprofloxacin hydrochloride raw materials. Method A is for drug
      content and the determination of related compounds eluting before the drug,
      including the ethylenediamine analog of ciprofloxacin. Method B may be used for
      the determination of fluoroquinolonic acid and other related compounds eluting
      after the drug. Both methods require a 5 microns Inertsil ODS2 column (150 x 4.6
      mm), a mobile phase containing tetrahydrofuran, acetonitrile and buffer (0.005 M
      1-hexane-sulphonic acid sodium adjusted to pH 3.0 with 0.1 M phosphoric acid);
      10:5:85 (v/v/v) for method A and 25:15:60 (v/v/v) for method B, and a flow rate
      of 1 ml min-1. Detection for method A is at 254 nm; a programmable variable
      wavelength detector is required for method B: 254 nm for 12 min, then 220 nm for
      23 min. The limit of quantitation of the related compounds was 0.05% or less. The
      precision of the assay method was lower than 1.0%. Drug content in four raw
      material samples ranged from 98.7% to 101.6% calculated with reference to the
      anhydrous substance. The water content in these samples ranged from 5.9% to 7.8%.
      Total impurity levels were 1.0% or lower. Levels of ethylenediamine analog and
      fluoroquinolonic acid were below 0.4%. A second analyst, using a different HPLC
      system and a column from a different supplier, repeated the analysis of two raw
      materials samples and obtained similar results.

PMID- 8738196
TI  - High-performance liquid chromatographic determination of 1-benzyl-1H-indazol-3-ol
      in benzydamine in pharmaceutical formulations.

PMID- 8738197
TI  - Disposition of poloxamer 407 in rats following a single intraperitoneal injection
      assessed using a simplified colorimetric assay.

PMID- 8738198
TI  - How to classify infections in intensive care units--the carrier state, a
      criterion whose time has come?

PMID- 8738199
TI  - The provision of food and catering services in hospital.
AB  - The supply of food to patients and staff is the responsibility of hospital
      support services. This article considers the provision of catering services and
      the production of safe food in hospitals in the UK. The responsibilities of food
      handlers and the role of the infection control team, the environmental health
      officer and the occupational health staff are also described.

PMID- 8738200
TI  - Fluconazole versus oral polyenes in the prophylaxis of immunocompromised
      patients: a cost-minimization analysis.
AB  - This study compares 100 mg daily fluconazole with oral polyenes four times daily
      in the prophylaxis of fungal infections in immunocompromised patients, to
      determine a cost-minimization strategy. Data was gathered through a literature
      survey and clinical interviews conducted in nine different UK hospitals. This was
      used to construct a decision tree, modelling the drug choices available to a
      clinician at various stages of a patient's treatment, and assigning probabilities
      to the different corresponding outcomes. UK cost data were fed into this model to
      determine the expected cost per patient of the different prophylaxis strategies.
      Two different patient groups were considered: chemotherapy-only patients, and
      bone-marrow-transplant (BMT) patients who have higher risks of fungal infection.
      Probabilities derived from the literature suggest that a cost-minimization
      strategy to manage both chemotherapy patients and BMT patients is to administer
      oral fluconazole, both as prophylaxis and as first line treatment, against
      superficial fungal infection. Probabilities gathered from clinical interviews
      yield similar results, suggesting that the cost-minimization strategy with
      chemotherapy-only patients is to administer oral polyenes as prophylaxis, and
      oral fluconazole in case of superficial fungal infection, while for BMT patients
      it is a combination of fluconazole and oral polyenes as prophylaxis, with oral
      fluconazole for the treatment of superficial fungal infections. Using the
      probabilities from the literature, the lowest cost strategies produce an expected
      cost of pounds 567.20 for chemotherapy-only patients, and an expected cost of
      pounds 804.87 for BMT patients for a course of treatment lasting from seven to 28
      days. The clinical interview probabilities produce expected costs of pounds
      826.48 and pounds 1529.43, respectively. Sensitivity analysis was then conducted,
      and it was found that in the majority of cases, using the literature
      probabilities, the cost-minimizing strategy remained prophylaxis with oral
      fluconazole. The sensitivity analysis for chemotherapy-only patients using the
      interview probabilities tended to favour oral polyenes as the cost-minimization
      strategy, whereas for BMT patients the sensitivity analysis favoured a
      combination of fluconazole and oral polyenes in the majority of cases. The key
      economic advantage of prophylaxis with fluconazole or a combination of
      fluconazole with oral polyenes in the prophylaxis of fungal infection in
      immunocompromised patients, results from the reduction of the expected cost of
      subsequent fungal infection among those who are most at risk.

PMID- 8738201
TI  - Consecutive isolation of homologous strains of methicillin-resistant and
      methicillin-susceptible Staphylococcus aureus from a hospitalized child.
AB  - A multiply resistant, methicillin-resistant Staphylococcus aureus was repeatedly
      isolated from the anterior nares of a premature neonate hospitalized in an
      intensive-care unit and treated with multiple courses of antibiotics. Two months
      following cessation of antibiotic therapy, a strain of S. aureus with a similar
      antibiotic resistance profile, but susceptible to methicillin, was isolated from
      three consecutive nasal swabs. Total DNA of the methicillin-susceptible and 
      resistant isolates was digested with SmaI and resolved by pulsed-field gel
      electrophoresis. The SmaI restriction profile of the susceptible isolate was
      similar to that of the resistant one except for the replacement of a 207-kb
      fragment by a 147-kb fragment. In Southern hybridization, a mecA-specific probe
      hybridized to the 207-kb SmaI fragment of the methicillin-resistant strain but
      not to DNA of the susceptible strain. These results suggest that loss of the mecA
      gene can occur in vivo when antibiotic selective pressure is removed.

PMID- 8738202
TI  - A prospective audit of wound infection rates after caesarean section in five West
      Yorkshire hospitals.
AB  - A three month prospective audit of wound infection following emergency and
      elective caesarean section was carried out in five West Yorkshire hospitals.
      Among 4076 women undergoing delivery in the five obstetric departments, the
      caesarean rate was 15.4%. The overall infection rate was 45/628 (7.2%) with a
      range of 2.5-17.2% between the five centres. The infection rate was 14/226 (6.2%)
      when antibiotics were used compared with 31/402 (7.7%) without antibiotics. The
      use of prophylactic antibiotics made no significant difference to the infection
      rate, which did not correlate with duration of labour or of ruptured membranes.
      The number of vaginal examinations correlated with the infection rate. In
      conclusion, the caesarean section rate observed was higher than that estimated
      for the UK as a whole, but was distorted by one centre with a high rate. For the
      other four hospitals the caesarean rate was unexceptional. The ratio of emergency
      to elective operations was comparable with recently reported values in the UK and
      the wound infection rate was within the widely varying limits found in previous
      studies. In view of the relatively low infection rate recorded without
      antibiotics, in the interests of cost effectiveness, prophylaxis may be limited
      in future to selected women at high risk. Because this was an audit rather than a
      randomized study we cannot exclude that this is already happening on an empirical
      basis.

PMID- 8738203
TI  - Outbreak of severe Pseudomonas aeruginosa respiratory infections due to
      contaminated nebulizers.
AB  - During the six months from January-June 1994, 10 cases of severe and 11 of less
      severe pulmonary infection caused by Pseudomonas aeruginosa were diagnosed in
      patients with chronic obstructive airways disease. Possible sources were
      evaluated. P. aeruginosa was isolated from four of the 22 nebulizers tested. The
      relationship of isolates from the patients and nebulizers was confirmed by sero-
      and phage-typing, and by arbitrarily-primed polymerase chain reaction (AP-PCR).
      Three types were identified and the distribution of types in patients with severe
      infection was as follows (one patient had a multiple infection). Type I was
      isolated from two nebulizers and from sputa, and/or blood and/or bronchial
      protected specimen brush samples or bronchial lavage fluid from four patients.
      Type II came from the sputa of three patients and a third nebulizer; and type III
      from sputa and/or blood of four further patients and another nebulizer. The data
      provided evidence for the relation between P. aeruginosa as a cause of infection
      and the contamination of the nebulizers. When nebulizer mouthpieces were changed
      every 24 h and sterilized between patients, no more contamination occurred, and
      the outbreak ceased.

PMID- 8738204
TI  - Bacterial contamination of autologous bone marrow during processing.
AB  - As part of an audit of the processing of autologous bone marrow, we found that
      marrow was often contaminated with organisms potentially pathogenic to
      neutropenic recipients. One of 14 marrows studied was found to be contaminated
      before the processing stage and five others became contaminated during
      processing. The organisms isolated at these stages were Propionibacterium sp.,
      coagulase-negative staphylococci, Staphylococcus aureus and coryneforms,
      suggesting that the skin was the likely source of contamination. Five out of the
      11 marrows returned to patients were found to be contaminated after thawing. Two
      of these were marrows previously shown to be contaminated with coagulase-negative
      staphylococci before freezing, and from these coagulase-negative staphylococci
      were isolated again, in one case the strains were indistinguishable. New
      organisms isolated after thawing included Bacillus sp. and Corynebacterium
      sporogenes suggesting contamination from the environment. No infections
      attributable to these organisms were demonstrated in any of the patients studied.

PMID- 8738205
TI  - The relationship between intraoperative contamination of the lower respiratory
      tract and postoperative chest infection.

PMID- 8738206
TI  - Prediction of signal peptide functional properties: a study of the orientation
      and angle of insertion of yeast invertase mutants and human apolipoprotein B
      signal peptide variants.
AB  - A number of studies have introduced mutations into the yeast invertase signal
      peptide, using it as a model system to elucidate features for targeting,
      translocation and intracellular transport. Using molecular modelling of the
      invertase signal peptide we have analysed the hydrophobicity potential and the
      change in dielectric constant of the energy transfer, when the molecule moves
      from a hydrophobic to a hydrophilic phase at the simulated hydrophobic
      hydrophilic interface. This modelling has been carried out on wild type and
      mutant invertase signal peptides of altered function, previously reported in the
      literature. While the predicted angle of insertion correlates with the measured
      extent of invertase secretion, with an optimum angle of 45 degrees, mutations
      that change the angle of orientation reduce the extent of invertase secretion. We
      have applied these same molecular modelling principles to the naturally occurring
      variants of the human apolipo-protein B (apoB) signal peptide, that confer a
      secretion defective phenotype when fused to yeast invertase and expressed in
      yeast. Our modelling thus identifies a strong correlation between the predicted
      angle of insertion of the signal peptide into the membrane and its ability to
      direct secretion.

PMID- 8738207
TI  - Effect of Lys-->Arg mutation on the thermal stability of Cu,Zn superoxide
      dismutase: influence on the monomer-dimer equilibrium.
AB  - The thermal stability of two single (K3R, K67R) and one double (K3R-K67R) mutants
      of Xenopus laevis B Cu, Zn superoxide dismutase has been studied to test Lys -->
      Arg substitution as an 'electrostatically conservative' strategy to increase
      protein stability. The K3R mutant displays an increased thermostability with
      respect to the wild-type enzyme, whilst a decreased stability was observed in the
      case of the K67R and K3R-K67R mutants. Concentration dependence of the apparent
      inactivation constant (kapp) of the latter mutants, as compared to that of the
      wild type enzyme and K3R mutant, indicates that their higher sensitivity to heat
      inactivation is due to a perturbation of the dimer association. These results are
      confirmed also by fluorescence anisotropy measurements of the internal probe
      Tyr149. The possible role of Arg67 in perturbing the dimer dissociation
      equilibrium toward the monomeric form is discussed.

PMID- 8738208
TI  - A structurally derived consensus pattern for theta class glutathione
      transferases.
AB  - We have recently determined the first crystal structure of a theta class
      glutathione transferase. We have aligned the amino acid sequences of members of
      the family using the crystal structure as a guide. The alignment has revealed a
      consensus pattern of residues that first identifies a protein as belonging to the
      glutathione transferase superfamily, and second is able to distinguish theta
      class members from other classes of glutathione transferases. The consensus
      residues unique to the theta class are found to cluster mostly on the hydrophilic
      surface and flanking loops of helix 2, a region found to be structurally diverse
      amongst crystal structures of the different glutathione transferase classes. When
      the consensus pattern was scanned against sequence databases, a number of matches
      were made with proteins not formally identified as glutathione transferases. Some
      of these matches indicated that several stress-related proteins belong to the
      theta class GST family.

PMID- 8738209
TI  - Predicted ligand interactions of 3'5'-cyclic nucleotide-gated channel binding
      sites: comparison of retina and olfactory binding site models.
AB  - Cyclic nucleotide-gated channels (CNGC) open in response to the binding of 3'5'
      cyclic nucleotides. Members of the CNGC family vary as much as 100-fold in their
      ability to respond to cAMP and cGMP. Molecular models of the nucleotide binding
      domains of the bovine retina and catfish and rat olfactory CNGCs were built from
      the crystal structure of cAMP bound to catabolite gene activator protein (CAP)
      with AMMP, a program for molecular mechanics and dynamics. The nucleotide
      conformation can be predicted from the number of strong and weak interactions
      between the purine ring and the binding site. The amino acids predicted to be
      important for determining the nucleotide affinity and specificity are residues
      61, 83 (mediated through a water molecule), 119 and 127 (CAP sequence numbers)
      which interact with the purine ring. These residues also dictate the conformation
      of the ligand in the binding pocket. cGMP is preferentially bound in the syn
      conformation in bovine retina, bovine olfactory and rat olfactory CNGCs due to
      Thr83, while either conformation can bind in catfish olfactory CNGC. cAMP is
      predicted to bind either in syn or anti conformation, depending on the
      interaction with residue 119: the anti conformation is preferentially bound in
      olfactory CNGCs.

PMID- 8738210
TI  - Incorporation of an unnatural amino acid in the active site of porcine pancreatic
      phospholipase A2. Substitution of histidine by 1,2,4-triazole-3-alanine yields an
      enzyme with high activity at acidic pH.
AB  - The effect of the substitution of the active site histidine 48 by the unnatural
      1,2,4-triazole-3-alanine (TAA) amino acid analogue in porcine pancreas
      phospholipase A2 (PLA2) was studied. TAA was introduced biosynthetically using a
      his-auxotrophic Escherichia coli strain. To study solely the effect of the
      substitution of the active site histidine, two nonessential histidines (i.e.
      His17 and His115) were replaced by asparagines, resulting in a fully active
      mutant enzyme (His-PLA2). In this His-PLA2 the single histidine as position 48
      was substituted by TAA with an incorporation efficiency of about 90%, giving a
      mixture of His-PLA2 and TAA-PLA2. Based on the charge difference at acidic pH,
      both forms could be separated by FPLC, allowing for the purification of TAA-PLA2
      free from His-PLA2. At pH 6, TAA-PLA2 has a fivefold reduced activity compared
      with His-Pla2. This reduced activity paralells a reduced rate of covalent
      modification with p-nitrophenacyl bromide of TAA-PLA2 compared with His-PLA2.
      Competitive inhibition gave comparable IC50 values for WT-PLA2, His-PLA2 and TAA
      PLA2. These results indicate that the reduction in activity is not caused by a
      different affinity for the substrate, but more likely results from a reduced kcat
      value in TAA-PLA2. The enzymatic activities for native and mutant PLA2s were
      measured at different pH values. For WT-PLA2 and His-PLA2 the activity is optimal
      at pH 6 and is strongly deminished at acidic pH, with no observable activity at
      pH 3. In contrast, TAA-PLA2 is as active at pH 3 as at pH 6. Most likely, the
      decrease in activity observed for WT-PLA2 and His-PLA2 is caused by the
      protonation of the active site His48, which is the general base involved in the
      activation of the nucleophilic water molecule. In TAA-PLA2, however, the active
      site residue TAA48 is unprotonated at both pH 3 and 6 as a result of the low pKa
      of TAA compared with histidine.

PMID- 8738211
TI  - The relative positions of alanine residues in the hydrophobic core control the
      formation of two-stranded or four-stranded alpha-helical coiled-coils.
AB  - The objective of this study was to investigate the positional effect of
      hydrophobic interactions in the alpha-helical interface in controlling the
      formation of two-stranded and four-stranded coiled-coils. Two disulfide-bridged
      antiparallel coiled-coils were designed which differ only in the position of a
      single Ala residue in the middle heptad: in peptide 2H the Ala residues are in
      register (in the same rung), while in peptide 4H they are not. Data from size
      exclusion chromatography and sedimentation equilibrium experiments showed that
      under benign conditions peptides 2H and 4H were two-stranded and four-stranded
      coiled-coils respectively. These results, in conjunction with molecular modeling
      studies, suggests that when four Ala residues are in the same plane of a
      potential four-stranded coiled-coil, the small side chains of Ala would create a
      large cavity in the hydrophobic interface of the potential four-stranded
      structure which is destabilizing and favors the two-stranded, disulfide-bridged
      coiled-coil. In contrast, an alternating Leu-Ala hydrophobic packing in the two
      planes distributes the potential cavity over a larger region, which may be
      partially filled by minor adjustments of the neighboring Leu side chains. As a
      result, there is still sufficient hydrophobic contact to maintain the four
      stranded structure.

PMID- 8738212
TI  - Production and characterization of anti-human interferon gamma receptor antibody
      fragments that inhibit cytokine binding to the receptor.
AB  - Three single-chain antibody fragments that recognize the extracellular human
      interferon gamma receptor alpha-chain (IFN gamma R), and inhibit the binding of
      human IFN gamma, have been produced in Escherichia coli. These fragments are
      derived from murine anti-receptor monoclonal antibodies, and comprise the
      variable heavy (VH) domain linked to the variable light (VL) chain through a 15
      amino acid linker [(GGGGS)3]. Using surface plasmon resonance technology
      (BIAcore), the soluble proteins were shown to retain a high affinity for
      recombinant IFN gamma R, and by radioimmunoassay to possess a high inhibitory
      activity towards IFN gamma-binding to human Raji cells. The antibody fragments
      most likely recognize epitopes that overlap the cytokine binding site on the
      receptor surface. Attempts to dissect further the antibodies to isolated VH- and
      VL-chains and to synthetic linear and cyclic peptides derived from the individual
      complementarity determining regions failed to afford fragments with significant
      IFN gamma R binding affinity. Nevertheless, these native-like variable region
      fragments and petidomimetics derived from them are of interest in the design of
      novel IFN gamma R antagonists.

PMID- 8738213
TI  - Double-site ricin B chain mutants retain galactose binding.
AB  - Three distinct double-site and two single-site ricin B chain (RTB) mutants were
      expressed in Spodoptera frugiperda insect cells and purified from infected cell
      supernatants. The yields of recombinant proteins were 0.01-0.2 mg/l. The purity
      after monoclonal antibody affinity chromatography was 1-20%. The mutant proteins
      were soluble, immunoreactive with monoclonal antibodies and polyclonal antibodies
      to RTB and demonstrated molecular weights of 32 kDa, similar to plant RTB. All
      three double-site and both single-site mutants bound asialofetuin and mammalian
      cell surfaces based on an asialofetuin ELISA and cell binding immunofluorescence
      assay. While one double-site mutant, W37S/Y248S, had a 1 log drop in sugar
      binding, the other two double-site mutants W37S/Y248H and D22E/D234E had 2 log
      reductions in sugar binding. Each mutant reassociated efficiently (25-75%) with
      plant ricin A chain (RTA) to form cytotoxic heterodimers. The concentration of
      protein required to reduce protein synthesis 50% (ID50) was 1 log higher than
      plant ricin for W37S/Y248S-RTA and the single-site mutant heterodimers, Q35N-RTA
      and D22E-RTA and 2 logs higher than plant ricin for the other two double-site
      mutant heterodimers. The results suggest amino acid residues in both the 1 alpha
      and 2 gamma subdomains of RTB participate in sugar binding. However, other
      subdomains must contribute to the avidity of ricin for cell surface
      oligosaccharides.

PMID- 8738214
TI  - Calcium modulates circadian variation in cAMP-stimulated melatonin in chick
      pineal cells.
AB  - In chick pineal cells, melatonin synthesis is regulated by both calcium and cAMP.
      Calcium-dependent regulation of melatonin is suggested by the monotonic decrease
      in melatonin observed with decreasing extracellular calcium ion concentrations
      ([Ca2+]0), the stimulation of melatonin with Bay K8644, and the inhibition of
      nocturnal melatonin by several calmodulin antagonists. At submicromolar [Ca2+]0,
      a stimulation of melatonin was observed in the presence of 8-Br cAMP, but not
      with Bay K8644, suggesting that this amount of stimulation of melatonin by 8-Br
      cAMP is independent of Ca2+ influx through dihydropyridine-sensitive Ca2+
      channels. At micromolar [Ca2+]0, there was a further increase in the stimulation
      of melatonin by 8-Br cAMP that was not blocked by nifedipine, a dihydropyridine
      sensitive Ca2+ channel antagonist. Micromolar [Ca2+]0 is required for the greater
      stimulation of melatonin by 8-Br cAMP during the night than during the day.
      Melatonin was stimulated by 8-Br cAMP to higher levels during the night than
      during the subjective day under normal [Ca2+]0 (1.3 mM). This difference in the
      amount of melatonin stimulated by 8-Br cAMP during the subjective night versus
      the subjective day was blocked by lowering [Ca2+]0 to a submicromolar
      concentration (0.2 microM). Both nifedipine and calmidazolium partially blocked
      nocturnal increases in melatonin, but were ineffective during the day. These
      results suggest that Ca2+ plays an important role in the differential ability of
      cAMP to stimulate melatonin during the night versus the day.

PMID- 8738216
TI  - Distribution of NMDA and AMPA receptors in the cerebellar cortex of rhesus
      macaques.
AB  - The distribution of glutamate receptors in the cerebellar cortex of the rhesus
      macaque was examined by light microscopic immunocytochemistry using an antibody
      specific to the N-methyl-D-aspartate (NMDA) R1 receptor subunit (i.e. NMDAR1) as
      well as antibodies specific to alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA) receptor subunits (i.e. GluR1, GluR2/3, and GluR4). NMDAR1
      immunolabeling was most prevalent in the Purkinje cell perikarya and dendrities,
      but was also significant in the stellate and basket cells of the granular layer
      and Golgi cells of the molecular layer. On the other hand, GluRl and GluR4
      immunolabeling was concentrated principally in the processes of the Bergmann glia
      located in the vicinity of the Purkinje cell perikarya. Although GluR2/3
      immunolabeling also occurred in these Bergmann glia processes as well as in the
      Bergmann fibers, it was more pronounced in the Purkinje cell perikarya and
      dendrites; additionally, significant GluR2/3 labeling was evident in the stellate
      and basket cells of the molecular layer and medium-size soma of the granular
      layer (most likely Golgi cells). In situ hybridization histochemistry (ISHH),
      using cRNA probes to NMDAR1. GluR1.GluR2, and GluR3, showed glutamate receptor
      mRNA distribution patterns consistent with those disclosed in the
      immunocytochemical study. Furthermore, the ISHH findings suggest that the
      positive immunocytochemical labeling of Purkinje cells with the GluR2/3 antibody
      is most likely due to the gene expression of both GluR2 and GluR3 AMPA receptor
      subtypes. Taken together, the results are potentially important for the
      elucidation of mechanisms that control aspects of cerebellar function, such as
      long-term depression.

PMID- 8738215
TI  - Pituitary adenylate cyclase activating polypeptide-immunoreactive sensory neurons
      innervate rat adrenal medulla.
AB  - Rat adrenal chromaffin cells were invested by a dense network of nerve fibers
      immunoreactive to pituitary adenylate cyclase activating polypeptide-38 (PACAP
      IR). Immunohistochemical studies demonstrated the presence of PACAP-IR in nodose
      and dorsal root ganglion cells, but not in neurons of the intermediolateral cell
      column and other autonomic nuclei of the thoracic and upper lumbar spinal cord.
      Somata of the T7 to T12 paravertebral ganglia were PACAP-negative. A few lightly
      labeled neurons were occasionally noted in the dorsal motor nucleus of the vagus.
      Injection of the retrograde tracer Fluorogold into the left adrenal medulla 3
      days prior to sacrifice resulted in the labeling of a population of neurons in
      the ipsilateral spinal cord intermediolateral cell column (T1 to L1), ipsilateral
      and contralateral nodose ganglia and ipsilateral dorsal root ganglia from T7 to
      T10 inclusive. A small number of lightly labeled somata was occasionally noted in
      the dorsal motor nucleus of the vagus. Combined retrograde tracing and PACAP
      immunohistochemistry showed that a population of Fluorogold-containing nodose and
      dorsal root ganglion cells were also PACAP-positive. Pre-treatment of the rats
      with capsaicin caused a marked reduction of the PACAP-IR in the adrenal gland as
      well as in the superficial layers of the dorsal horn and caudal spinal trigeminal
      nucleus. These findings, in conjunction with the apparent absence of PACAP-IR in
      spinal sympathetic preganglionic neurons, sympathetic postganglionic neurons, and
      dorsal motor nucleus of the vagus, raise the possibility that PACAP-IR fibers
      observed in the adrenal medulla are primarily sensory in origin. As a corollary,
      catecholamine secretion from chromaffin cells may be modulated by the peptidergic
      sensory afferents in addition to the cholinergic sympathetic preganglionic nerve
      fibers.

PMID- 8738217
TI  - Effects of discrete kainic acid-induced hippocampal lesions on spatial and
      contextual learning and memory in rats.
AB  - Substantial information is available concerning the influence of global
      hippocampal lesions on spatial learning and memory, however the contributions of
      discrete subregions within the hippocampus to these functions is less well
      understood. The present investigation utilized kainic acid to bilaterally lesion
      specific areas of the rat hippocampus. These animals were subsequently tested on
      a spatial orientation task using a circular water maze, and on an
      associative/contextual task using passive avoidance conditioning. The results
      indicate that both the dorsal CA1 and the ventral CA3 subregions play important
      roles in learning. Specifically, CA1 lesions produced a deficit in the
      acquisition of the water maze task and a significant memory impairment on the
      passive avoidance task. CA3 lesions also caused learning deficits in the
      acquisition of the water maze task, and produced even greater impairments in
      performance on the passive avoidance task. We conclude that CA1 and CA3
      hippocampal subregions each play significant roles in the overall integration of
      information concerning spatial and associative learning.

PMID- 8738218
TI  - Ischemic tolerance in moderately symptomatic gerbils after unilateral carotid
      occlusion.
AB  - Ischemic tolerance following transient global cerebral ischemia has drawn
      considerable attention because of the putative cell defense mechanism which may
      be inducible by ischemic stress. The purpose of this study is to investigate the
      inducibility of ischemic tolerance in moderately symptomatic gerbils after
      unilateral carotid occlusion. Adult Mongolian gerbils were used. Under ether
      inhalation, the right common carotid artery was occluded for up to 30 min with an
      aneurysmal clip. Immediately after occlusion, neurological signs and motor
      function were evaluated and gerbils with moderate signs were selected for
      investigation of ischemic tolerance. Ischemia for 30 min to gerbils with moderate
      signs constantly caused neuronal death in the caudoputamen, but it was prevented
      by pretreatment with 10 min ischemia which was reversible but strong enough to
      produce heat shock protein 70. The results show that ischemic tolerance can be
      induced after hemispheric cerebral ischemia as in the case of global cerebral
      ischemia and suggest that ischemic tolerance may be relevant in human stroke.

PMID- 8738219
TI  - Reduced sensorimotor reactivity following traumatic brain injury in rats.
AB  - The present study examined sensorimotor reactivity in rats following traumatic
      brain injury (TBI). Moderate injury was induced with midline fluid percussion in
      some of the rats. Others received identical surgery, but were not injured (sham
      injured rats), or received neither surgery nor injury (naive rats). All rats were
      evaluated in acoustic and/or tactile startle procedures. At 8 days post-injury,
      the sensorimotor reactivity of TBI rats to acoustic stimuli was severely reduced
      compared to that of sham-injured rats. This TBI-induced deficit was enduring (>
      30 days). In a separate experiment, greater sensorimotor reactivity was observed
      with tactile (vs. acoustic) stimulation in both TBI and naive rats although
      startle amplitudes for the TBI rats were lower than control levels for both types
      of stimuli. These results suggest that sensorimotor reactivity is altered by TBI
      and that the startle procedure is a promising method for investigation of
      information processing alterations following TBI.

PMID- 8738220
TI  - S-100-immunoreactivity in spontaneously active snail neurons.
AB  - The distribution of S-100-immunoreactive material was examined in the central
      nervous system of the gastropod snail. Helix pomatia, and electrophysiological
      properties of S-100-positive neurons were characterized. Immunocytochemical
      studies revealed S-100-like protein to be present in neurons localized in the
      cerebral, left parietal, and visceral ganglia, but not in glial cells. Among the
      immunoreactive neurons we identified the giant cells LPa3 and LPa4. Western blots
      showed a single S-100-immunoreactive band at 12-14 kDa. S-100-positive neurons
      are distinguished by spontaneous discharge activity in a beating or bursting mode
      and a prominent Ca(2+)-activated potassium outward current. Our result show that
      a S-100-like protein exclusively present in neurons of the Helix central nervous
      system is correlated with spontaneous discharge activity of these cells.

PMID- 8738221
TI  - Medial amygdaloid suppression of predatory attack behavior in the cat: I Role of
      a substance P pathway from the medial amygdala to the medial hypothalamus.
AB  - The medial amygdala is known to powerfully suppress predatory attack behavior in
      the cat, but the mechanisms underlying such modulation remain unknown. The
      present study tested the hypothesis that medial amygdaloid suppression of
      predatory attack is mediated, in part, by a pathway from the medial amygdala to
      the medial hypothalamus which utilizes substance P as a neurotransmitter.
      Stimulating electrodes were implanted into the medial amygdala and cannula
      electrodes were implanted into both the medial and lateral hypothalamus.
      Predatory attack behavior was elicited by electrical stimulation of the lateral
      hypothalamus. In the first phase of the study, paired trials compared attack
      latencies of single stimulation of the lateral hypothalamus with those following
      dual stimulation of the lateral hypothalamus and medial amygdala. Attack
      latencies were significantly elevated following dual stimulation of the medial
      amygdala and lateral hypothalamus. In the second phase of the study, dose and
      time dependent decreases in response suppression were noted following the
      infusion of the substance P (NK1) receptor antagonist, CP96.345 (in doses of
      0.05, 0.5 and 2.5 nmol) into the medial hypothalamus. In third phase of the
      study, the effects of microinjections of the substance P receptor agonist,
      [Sar9.Met(O2)11]-substance P (in doses of 0.5, 1.0 and 2.0 nmol), directly into
      the medial hypothalamus upon lateral hypothalamically elicited predatory attack
      behavior were determined. Microinfusion of this drug elevated attack response
      latencies in a dose- and time-dependent manner. In addition, pretreatment with
      CP96,345 into the medial hypothalamus blocked the suppressive effects of
      subsequent delivery of [Sar9,Met(O2)11]-substance P into the same medial
      hypothalamic site. Other parts of the study demonstrated the presence of: (1)
      high densities of substance P receptors in the ventromedial hypothalamus, and (2)
      neurons that are positively labeled for substance P that project from the medial
      amygdala to the ventromedial hypothalamus as demonstrated by retrograde labeling
      with Fluoro-Gold. These findings provide support for the hypothesis that medial
      amygdaloid suppression of lateral hypothalamically elicited predatory attack
      behavior includes a substance P pathway from the medial amygdala to the medial
      hypothalamus. The findings further suggest that stimulation of the medial
      amygdala activates substance P receptors in the medial hypothalamus, thus
      triggering an inhibitory mechanism from the medial to the lateral hypothalamus,
      resulting in suppression of predatory attack behavior.

PMID- 8738222
TI  - Medial amygdaloid suppression of predatory attack behavior in the cat: II. Role
      of a GABAergic pathway from the medial to the lateral hypothalamus.
AB  - The medial amygdala is known to powerfully suppress predatory attack behavior
      elicited by electrical stimulation of the lateral hypothalamus of the cat. In the
      preceding paper, it was shown that the initial limb of a pathway subserving
      suppression of predatory attack from the medial amygdala to the lateral
      hypothalamus projects to the ventromedial hypothalamus and its functions are
      mediated by substance P. The present study tested the hypothesis that the second
      limb of the pathway subserving medial amygdaloid suppression of predatory attack
      behavior projects from the medial to lateral hypothalamus and its functions are
      mediated by GABA. Cannula electrodes were implanted into the lateral hypothalamus
      for elicitation of predatory attack behavior as well as for the microinfusion of
      GABA compounds. Monopolar stimulating electrodes were implanted into sites within
      the medial amygdala from which subseizure levels of stimulation could suppress
      predatory attack behavior. Initially, the effects of dual stimulation of the
      medial amygdala and lateral hypothalamus upon response latencies for predatory
      attack were compared with single stimulation of the lateral hypothalamus alone.
      Dual stimulation was shown to significantly suppress predatory attack elicited
      from the lateral hypothalamus. Then, the GABAA receptor antagonist, bicuculline,
      was microinjected into sites within the lateral hypothalamus from which predatory
      attack was elicited in doses of 0.015, 0.075 and 0.15 nmol and paired trials of
      single and dual stimulation were again repeated in a manner identical to that
      applied prior to drug administration. Drug infusion produced a blockade of medial
      amygdaloid suppression of predatory attack in a time- and dose-dependent manner.
      Conversely, microinfusions of the GABAA receptor agonist, muscimol (10, 25 and 50
      pmol), into the same lateral hypothalamic 'attack' site in the absence of medial
      amygdaloid stimulation suppressed predatory attack, thus simulating the effects
      of medial amygdaloid stimulation. Furthermore, pretreatment with bicuculline
      microinjected into the lateral hypothalamus blocked the suppressive effects of
      substance P, that was infused into the ventromedial hypothalamus, upon predatory
      attack. Receptor autoradiography demonstrated the presence of high affinity
      binding for GABAA receptors in the lateral hypothalamus. A combination of
      immunocytochemical and retrograde axonal tract tracing procedures, in which
      Fluoro-Gold was microinjected into the lateral hypothalamic attack sites,
      revealed the presence of populations of neurons labeled for both Fluoro-Gold and
      GABA in the ventromedial hypothalamus. These findings provide new evidence for
      the existence of a pathway from the medial to lateral hypothalamus whose
      functions are mediated by GABA. Thus, the overall findings provide support for
      the view that the pathway from the medial amygdala to the lateral hypothalamus
      underlying suppression of predatory attack behavior involves a two-neuronal arc:
      the first neuron projects from the medial amygdala to the medial hypothalamus and
      its functions are mediated by substance P: the second neuron involves a GABAergic
      pathway originating in the ventromedial hypothalamus and which projects to the
      lateral hypothalamus.

PMID- 8738223
TI  - Human motor unit activity during post-vibratory and imitative voluntary muscle
      contractions.
AB  - Applying mechanical vibration for short periods to a muscle tendon induces long
      lasting involuntary contractions which develop soon after the vibration offset in
      the previously vibrated muscle. In the present study, the question was raised as
      to whether these post-vibratory motor responses are mediated by the activity of
      supraspinal neural population or whether they may involve in addition some
      peripheral facilitatory influences operating at the motoneuronal level. To
      investigate this question, we analysed the unitary activity of 48 motor units
      belonging to the wrist extensor radialis muscles of the human hand, after
      attempting to classify them as slow or fast, during both post-vibratory and
      voluntary contractions having almost the same amplitudes and time-courses. The
      motor units were found to be activated in much the same way with both types of
      contraction. Similarities were observed as regards: the nature of the motor units
      activated, the order of recruitment of the motor unit population, the motor
      units' force recruitment thresholds, the mean interspike interval and the
      standard deviation. These analogies suggest that post-vibratory contraction may
      mainly involve a supraspinal tonic drive, but the possibility that these
      involuntary contractions may have a spinal origin cannot be completely ruled out.

PMID- 8738224
TI  - Effect of alkalizing agents on the processing of the beta-amyloid precursor
      protein.
AB  - We investigated the processing pathway of the amyloid precursor protein (APP) to
      the secretion of beta A4 under the treatment of ammonium chloride (NH4Cl),
      bafilomycin A1 (bafA1), or chloroquine, all three agents thought to raise the pH
      in acidic compartments. HEK-293 cells expressing wild-type APP (APPwt) and APP
      carrying the Swedish double mutation (APPswe) were affected in a different
      manner: while cells expressing APPswe decreased the secretion of beta A4 after
      treatment with bafA1 and NH4Cl, cells expressing APPwt compensated the drug
      induced decrease in beta A4 by an increased generation of alternative beta A4
      related peptides. Within cells APP accumulated, while the formation of a C
      terminal fragment of APP generated by beta-secretase was completely inhibited.
      Thus, BafA1 and NH4Cl reduced the secretion of beta A4 by inhibiting beta
      secretase. Treatment with chloroquine did not alter beta A4 secretion but,
      strikingly, resulted in an accumulation of intracellular beta A4. The effect of
      reduced APP endocytosis was studied by expressing APP molecules lacking the
      cytoplasmic domain (APPwt.delta. APPswe.delta). Truncation of APP reduced beta A4
      secretion from APPwt but not from APPswe. BafA1 and NH4Cl treatment inhibited the
      formation of beta A4 in cells expressing APPswe.delta but not APPwt.delta. With
      these constructs, chloroquine had no effect and no accumulation of intracellular
      beta A4 was observed. Since alkalizing agents still affected endocytosis
      deficient APP containing the Swedish double mutation, we suggest that the
      formation of beta A4 from this mutated APP takes place mainly in an acidic
      compartment along the constitutive secretory pathway. Much in contrast to this,
      beta A4 generation from APPwt appears to occur also in the endosomal/lysosomal
      compartment.

PMID- 8738225
TI  - Paired pulse facilitation of GABAergic IPSCs in ventral horn neurons in neonatal
      rat spinal cord.
AB  - Whole-cell patch-clamp recording of GABAergic inhibitory postsynaptic currents
      (IPSCs) were made in ventral horn neurons of neonatal rat lumbar spinal cord in
      slice. In contrast to the hippocampus where paired pulse depression is reported
      to be observed for GABAergic IPSCs, double pulse stimulation of GABAergic inputs
      resulted in enhancement in the amplitude of the second IPSC in the spinal ventral
      horn. The facilitation ratio was decreased during enhanced synaptic transmission
      by increasing Ca2+ concentration in the external recording solution. Baclofen and
      adenosine. which are reported to depress synaptic transmission by presynaptic
      mechanisms, depressed IPSCs and increased the facilitation ratio. A postsynaptic
      manipulation such as application of bicuculline or changing the driving force did
      not affect the facilitation ratio. These results suggest that paired pulse
      facilitation of GABAergic IPSCs observed in neonatal rat spinal ventral horn
      appears to be based upon a mechanism similar to that underlying frequency
      dependent facilitation of excitatory synaptic transmission, and is sensitive to
      presynaptic changes in synaptic strength.

PMID- 8738226
TI  - Differences among mouse strains in the regulation by mu, delta 1 and delta 2
      opioid receptors of striatal adenylyl cyclases activated by dopamine D1 or
      adenosine A2a receptors.
AB  - It is well established that the intensity of the morphine-induced locomotor
      stimulatory response in rodents is genetically determined. We have evaluated the
      ability of mu (DAMGO). delta 1 (DPDPE) and delta 2 ([D-Ala2]deltorphin II; DT-II)
      selective opioid receptor agonists to inhibit receptor-activated adenylyl cyclase
      activity. Previous studies have shown that dopamine D1 receptors are
      preferentially expressed in striatonigral neurons, while adenosine A2a receptors
      are preferentially expressed in striatopallidal neurons. Our results indicate
      that in striatum of wild-type CD1 mice as in rat. mu-agonists inhibit D1
      activated adenylyl cyclase, but were without inhibitory activity against A2a
      activated adenylyl cyclase. In all tested mouse strains, the delta 1 selective
      agonist, DPDPE, inhibited the A2a-activated adenylyl cyclase but not the D1
      activated enzyme. In contrast, the delta 2 agonist, DT-II, inhibited both D1 and
      A2a activated enzyme in all strains except DBA/2J, where DT-II did not inhibit D1
      activated adenylyl cyclase. In C57BL/6J mice, which are highly sensitive to
      morphine-induced motor stimulation, mu agonists were potent inhibitors of A2a
      activated adenylyl cyclase but did not inhibit the D1-activated enzyme, while mu
      opioids did not inhibit A2a-activated enzyme in DBA/2J mice which show little
      locomotor response to morphine. In CXBK mice, a strain with known deficiencies in
      mu-receptor expression, both forms of receptor-activated adenylyl cyclase were
      less sensitive than in CD1 mice to inhibition by DAMGO. The results suggest
      probable differences in the specific neural locations of opioid receptor subtypes
      in certain inbred strains of mice with varying sensitivities to the behavioral
      effects of morphine.

PMID- 8738227
TI  - Depletion of brain glutathione results in a decrease of glutathione reductase
      activity; an enzyme susceptible to oxidative damage.
AB  - Loss of the intracellular antioxidant glutathione (GSH) from the substantia nigra
      is considered to be an early event in the pathogenesis of Parkinson's disease
      (PD). While the cause of the loss is unclear, an imbalance in the enzymes
      associated with the synthesis, utilisation, degradation and translocation of GSH
      has been implicated. The enzyme glutathione reductase is also important in GSH
      homeostasis: it regenerates GSH from the oxidised from (GSSG). However, to date
      the activity and regulation of glutathione reductase in conditions such as PD
      have not been explored. In view of this we have measured the effects of GSH
      depletion on glutathione reductase activity of the rat brain. Other glutathione
      related enzymes were also measured. Using pre-weanling rats, brain GSH was
      depleted by up to 60% by subcutaneous administration of L-buthionine sulfoximine.
      The only enzyme affected by GSH depletion was glutathione reductase; its activity
      being reduced by approximately 40%. As GSH inactivates a number of oxidising
      species including peroxynitrite (ONOO-), we additionally investigated the
      susceptibility of glutathione reductase to ONOO- in vitro, using purified enzyme.
      ONOO- decreased glutathione reductase activity in a concentration dependent
      manner with an apparent 50% inhibition occurring at an initial concentration of
      0.09 mM. These data suggest that GSH is important in the maintenance glutathione
      reductase activity. This may arise in part from its ability to inactivate
      oxidising agents such as ONOO-.

PMID- 8738228
TI  - A subgroup of dorsal raphe serotonergic neurons in the cat is strongly activated
      during oral-buccal movements.
AB  - A subgroup of approximately 25% of dorsal raphe nucleus serotonergic neurons in
      cat was strongly activated in association with oral-buccal movements, such as
      chewing, licking, and grooming. The mean magnitude of increase in neuronal
      activity for these cells was approximately 100% above the spontaneous waking
      level. However, some of these cells were activated by as much as 200-300%. The
      neuronal activation frequently preceded the initiation of the movement and
      stopped abruptly in association with either pauses in the motor sequence or with
      its cessation. Most of the neurons in this subgroup were also strongly and
      preferentially activated by somatosensory stimuli applied to the head, neck, and
      face. During orientation to a strong or novel stimulus, the activity of these
      neurons fell silent for periods of 1-5 s. These data and results from our
      previous studies of medullary raphe neurons are discussed within the context of
      the general role of serotonin in tonic and central pattern generator-related
      motor activity.

PMID- 8738229
TI  - A functional medial preoptic nucleus (MPO) is required for scrotal thermal
      stimuli to alter the neuronal activity of thermoresponsive ventromedial
      hypothalamic (VMH) neurons.
AB  - Thermoresponsiveness of ventromedial hypothalamic (VMH) neurons to scrotal
      thermal stimulation was determined before and after microinjection of lidocaine
      into the medial preoptic nucleus (MPO). Male, urethane anesthetized Sprague
      Dawley rats, maintained colonically at 37 degrees C had VMH extracellular
      neuronal activity recorded following 3 cycles of scrotal thermal stimulation
      (localized, incremental heating and cooling, between 10 and 40 degrees C). Based
      on their thermal coefficients (TC), warm (WRN), cold (CRN) thermoresponsive and
      temperature non-responsive (TNRN) VMH neurons had their neuronal activity
      recorded following each cycle of scrotal thermal stimulation before and after MPO
      injections of sterile saline (300 nl volume) or 2% buffered lidocaine (200 ng).
      Thermoresponsiveness of all warm and cold VMH neurons to scrotal thermal
      stimulation was blocked by prior lidocaine administration into the MPO, effects
      that were reversed approximately 60 min after. However, MPO lidocaine
      administration caused no significant change in the thermal coefficients of VMH
      TNRNs to scrotal thermal stimulation. Results infer that a functional MPO is
      required for thermal afferent signals arising from the scrotum to reach
      thermoresponsive VMH neurons.

PMID- 8738230
TI  - Changes in regional cerebral blood flow during self-paced arm and finger
      movements. A PET study.
AB  - The purpose of this study was to identify the functional fields activated in
      relation to the self-paced proximal and distal arm movements. The regional
      cerebral blood flow (rCBF) was measured with positron emission tomography (PET)
      and 15O-labelled H2O (H2(15)O) in eight healthy subjects. All subjects performed
      the following three tasks: (1) repetitive opposition of thumb and index finger of
      the right hand, (2) repetitive co-contraction of biceps and tricepts brachii
      muscles of the right arm, and (3) rest. The mean rCBF change images for each task
      minus control was calculated and fields of significant rCBF changes were
      identified. Each movement activated different fields in the primary motor area
      (MI), the dorsal aspect of the premotor area (PMA) and the superior part of the
      prefrontal area (PFA) of the contralateral hemisphere. In these areas, arm fields
      were located relatively dorsally to the finger fields. In addition, specific
      fields in the ventral part of the PMA, the supplementary motor area (SMA), the
      superior parietal lobule (SPL) of the contralateral hemisphere, and the
      ipsilateral PFA were consistently activated during both movements. Due to a
      limited a field of view of the PET scanner in the axial direction, the PET scan
      could not cover the cerebellum. The results indicate that there may be
      somatotopical organization not only in the MI but also in the dorsal part of the
      PMA and the PFA, and that the specific fields in the ventral part of the PMA, the
      SMA, the SPL, and the PFA may be involved in self-paced movement.

PMID- 8738231
TI  - A learned odor decreases the number of Fos-immunopositive granule cells in the
      olfactory bulb of young rats.
AB  - Olfactory stimulation evokes a column of activity within the olfactory bulb
      extending from the glomerular layer to the granule cell layer that can be
      visualized with 2-deoxyglucose autoradiography, optical imaging, Fos protein
      immunohistochemistry and c-fos mRNA in situ hybridization. The Fos response to
      odors is typified by the activity of relatively few juxtaglomerular cells, which
      often occur in foci, and a large number of granule cells extending through much
      of the bulb. In this study, we characterized the granule cell response to an odor
      for which young rats had acquired a preference. Fos-like immunoreactive granule
      cells were quantified by image analysis, and densely stained cells were counted
      in a region previously shown to be responsive to peppermint odor. We found that
      odor-trained pups have about half the number of Fos-immunopositive superficial
      granule cells which respond to a learned odor than do control pups. We then
      determined whether there was a correlation between the juxtaglomerular cell
      response and the response of the superficial granule cells deep to those
      glomerular layer cells. We found a positive correlation between the number of
      juxtaglomerular cells and the number of granule cells demonstrating Fos
      immunoreactivity in both control and trained pups, a relationship that changed
      with early olfactory training.

PMID- 8738232
TI  - Effect of ethanol on extracellular 5-HT and glutamate in the nucleus accumbens
      and prefrontal cortex: comparison between the Lewis and Fischer 344 rat strains.
AB  - The present study investigated the impact of systemic (i.p.) ethanol
      administration on extracellular levels of serotonin and glutamate in the
      prefrontal cortex and the nucleus accumbens in Lewis and Fischer 344 rat strains
      using in vivo microdialysis. At 1.0 g/kg, ethanol elicited a significant increase
      in nucleus accumbens-dialysate levels of both 5-HT (44% +/- 16, P = 0.002) and
      glutmate (90% +/- 43, P = 0.009) in Lewis rats. In Fischer rats, there was no
      increase in 5-HT (6% +/- 7: P = 0.5), and a trend toward an increase in glutamate
      (88% +/- 46: P = 0.1). The 0.5 and 2.0 g/kg doses did not result in any
      significant change in extracellular 5-HT or glutamate in the nucleus accumbens or
      prefrontal cortex of either strain. The basal levels of glutamate, in both brain
      regions, were significantly lower in Lewis than in Fischer 344 rats. The basal
      levels of 5-HT were also lower in the nucleus accumbens of Lewis rats. These
      findings suggest that enhanced sensitivity of the mesoaccumbens 5-HT or glutamate
      systems to ethanol and/or inherent low basal levels of 5-HT or glutamate activity
      may be associated with the predisposition to alcohol-drinking behavior seen in
      Lewis rats.

PMID- 8738233
TI  - Effect of an NMDA receptor antagonist and a ganglioside GM1 derivative upon
      ethanol-induced modification of parameters of oxidative stress in several brain
      regions.
AB  - Dietary administration of ethanol to rats for 2 weeks was able to depress levels
      of glutathione (GSH) and Cu/Zn superoxide dismutase (SOD) in several brain
      regions. This was indicative of the generation of excess levels of reactive
      oxygen in treated animals. The potentially protective effect of both an NMDA
      receptor blocker (MK-801) and an internally esterified derivative of ganglioside
      GM1 (AGF2) upon ethanol-induced changes in these indices of oxidative stress, was
      studied. Both of these agents are reported to have neuroprotective properties,
      but neither was able to prevent ethanol-induced reduction of GSH and SOD levels
      in any brain area studied. In fact, both agents depressed SOD and GSH levels in
      midbrain independently of ethanol. MK-801 had a pronounced pro-oxidant potential,
      and when administered in combination with ethanol. GSH and SOD were reduced in
      midbrain and striatum to levels below those obtained with either agent alone. The
      pro-oxidant properties of ethanol may thus act independently of its actions upon
      the NMDA receptor. The protective properties of NMDA receptor inhibitors or
      gangliosides cannot be attributed to any antioxidant effect.

PMID- 8738234
TI  - Procaine microinjection into the lower midbrain increases brown fat and body
      temperatures in anesthetized rats.
AB  - A tonic inhibitory mechanism on heat production was studied by microinjecting
      procaine into various regions of the brain while recording temperature changes of
      the interscapular brown adipose tissue (IBAT) and rectum in urethane-anesthetized
      rats at room temperature of 23-25 degrees C. Procaine microinjected bilaterally
      (10%, 1.0 mu l/site, 1.5 mm to midline) into the midbrain and the upper- to mid
      pontine area of the reticular formation increased temperatures of the IBAT and
      rectum. The highest temperature rise (1.02 +/- 0.11 degrees C for IBAT, 0.64 +/-
      0.06 degrees C for rectum) with the shortest onset latency (1.5 +/- 0.3 min for
      IBAT, 4.6 +/- 1.1 min for rectum) was observed when procaine was injected into
      the lower midbrain (the area between 6 and 7 mm posterior to the bregma, and 6.5
      to 8.5 mm deep from the cortical surface). These regions include the retrorubral
      field, pedunculopontine tegmental nucleus, and rubrospinal tract. Procaine
      induced IBAT and rectal temperature increases were dose-dependent, and reproduced
      reliably from the same injection site of the same animal. Intravenous
      indomethacin, a prostaglandin H synthase inhibitor, did not affect procaine
      induced temperature rise, and propranolol, a beta-blocker, completely blocked it.
      These results suggest that microinjected procaine exerts its local anesthetic
      effect and release a tonic inhibition resulting in a disinhibition-induced
      temperature increase through the enhanced central sympathetic outflow. They
      support the hypothesis that a bilateral tonic inhibitory mechanism on heat
      production exists in the lower midbrain.

PMID- 8738235
TI  - Effect of a pharmacological stressor on glutamate efflux in the prefrontal
      cortex.
AB  - The anxiogenic beta-carboline, FG 7142 (20 mg/kg) significantly increased
      glutamate efflux in the prefrontal cortex of conscious rats as assessed by
      microdialysis. Pretreatment with the benzodiazepine receptor agonist, diazepam (5
      mg/kg), abolished this effect. These findings indicate that anxiogenic compounds
      produce an effect similar to physical stressors on the outflow of glutamate, and
      implicate the GABA/benzodiazepine receptor complex in the stress-induced
      activation of glutamate systems in the prefrontal cortex.

PMID- 8738236
TI  - Comparison of succinate dehydrogenase activity and soma size relationships among
      neurons in dorsal root ganglia of rats and cats.
AB  - Compared to dorsal root ganglion (DRG) neurons at L5 in rats, DRG neurons at L7
      in cat have a larger mean soma size, a bimodal rather than unimodal distribution
      of sizes and lower succinate dehydrogenase (SDH) activities for neurons of all
      sizes. In contrast to spinal motoneurons in both cats and rats, the larger DRG
      neurons have the higher SDH activities. The 10-20% higher SDH activity of DRG
      cells in rats than in cats may reflect, in part, a species difference of about
      40% in metabolic rates.

PMID- 8738237
TI  - Intracellularly applied anti-P70 antibody blocks the induction of abnormal
      membrane properties by pentylenetetrazole in identified Euhadra neurons.
AB  - Using the voltage-clamp technique combined with pressure injection, we have
      studied the action of pentylenetetrazole (PTZ) on identified Euhadra neurons by
      examining how the PTZ-induced changes in membrane properties are affected by an
      antibody against P70, a protein found in the experimentally-induced epileptogenic
      cortex of rats. Intracellular injection of anti-P70 antibody blocked the
      induction by PTZ; bursting activity with both of development of negative slope
      resistance region in the steady state 1-V curve and a reduction in the delayed
      outward potassium current. These results suggest a novel mechanism of action for
      PTZ, involving intracellular protein(s) which react with anti-P70 antibody.

PMID- 8738238
TI  - Microelectrophoretic application of SCH-23390 into the lateral septal nucleus
      blocks ethanol-induced suppression of LTP, in vivo, in the adult rodent
      hippocampus.
AB  - Ethanol intoxication produces deficits in the acquisition of new information and
      blocks the induction of hippocampal long-term potentiation (LTP), a candidate
      neurophysiological correlate for learning and memory. We report that, in adult
      rats, local application of the dopamine (DA) D1 receptor antagonist SCH-23390
      into the lateral septum (LS) blocks ethanol-induced suppression of LTP and
      alterations of paired-pulse responses in the dentate gyrus. This suggests a
      primary role for an extra-hippocampal circuit and neurotransmitter system
      mediating ethanol's ability to suppress LTP.

PMID- 8738239
TI  - Expression of mRNAs for preprotachykinin and nerve growth factor receptors in the
      dorsal root-ganglion following peripheral inflammation.
AB  - Nerve growth factor (NGF) plays a dynamic role in the control of substance P (SP)
      levels and synthesis in the dorsal root ganglion (DRG). In the present study, in
      situ hybridization was used to examine the change of preprotachykinin (PTT), trkA
      and p75 mRNAs levels in the DRG after the injection of complete Freund's adjuvant
      into the hindpaws of rats. Peripheral tissue inflammation increased PTT and p75
      mRNAs levels in the DRG, while trkA mRNA levels showed no change. These findings
      suggest that p75, in addition to trkA, also may be important in mediating the
      action of NGF on the synthesis of SP in the DRG following peripheral
      inflammation.

PMID- 8738240
TI  - Response to repetitive stimulation of AMPA receptors in patches excised from
      fields CA1 and CA3 of the hippocampus.
AB  - Patches excised from fields CA1 and CA3 of the hippocampus were used to study
      AMPA receptor responses to repetitive application of brief pulses of agonist.
      AMPA receptors in field CA1 exhibited a larger degree of paired-pulse depression
      and a slower recovery rate from desensitization than those from CA3 patches.
      Responses became progressively smaller during a train of short pulses (4 at 100
      Hz), an effect that was greater in CA1 than CA3 patches and that was blocked by a
      drug (cyclothiazide) that slows desensitization. Cyclothiazide also increased
      steady state currents during a long pulse of glutamate and had a lower EC50 for
      CA3 than CA1 AMPA receptors. These results suggest (i) that differences in the
      relative balance of flip vs. flop subunits affect the kinetic and pharmacological
      properties of AMPA receptors in vivo, and (ii) that the rate of recovery from
      desensitization may influence responses to the bursts of afferent activity
      commonly used to induce long-term potentiation.

PMID- 8738241
TI  - Amphetamine-induced Fos expression in globus pallidus is altered by frontal
      cortex injury.
AB  - Functional recovery from cortical injury may result from subcortical compensatory
      processes. This study examined basal gangliar expression of the immediate early
      gene c-fos after unilateral medial agranular cortex (AGm) ablation. In the
      ipsilateral dorsal globus pallidus of rats demonstrating neglect of contralateral
      stimuli (sacrificed 5 days postinjury), the numbers of amphetamine-induced Fos
      positive nuclei were reduced 37% compared to intact hemisphere values. These
      reductions were no longer apparent in recovered AGm-ablated rats (sacrificed 21 +
      days postinjury). These findings mirror in timing and direction the changes in
      Fos seen in dorsolateral striatum after AGm ablation.

PMID- 8738242
TI  - Fos expression in rat visual cortex induced by ocular input of ultraviolet light.
AB  - We used immunostaining for the cellular transcription factor Fos to assess
      patterns of neuronal activation in rat visual cortex during exposure to
      ultraviolet light. Exposure to monochromatic ultraviolet light (lambda max 360
      nm: half-bandwidth 8.8 nm, 10 microW/cm2 at eye level) induced strong expression
      of Fos immunoreactivity in the primary visual cortex and associated cortical
      visual areas of dark-adapted rats. The stimulatory effect of ultraviolet light on
      Fos expression was related to exposure duration, was independent of stimulus
      novelty or phase of the circadian cycle in which exposure occurred, and it was
      mediated by a mechanism located in the eye. These results demonstrate that ocular
      input of ultraviolet light is capable of altering neuronal activity in cortical
      structures involved in visual processing and are consistent with the hypothesis
      that rodents may use ultraviolet light for vision.

PMID- 8738243
TI  - Spatial and temporal frequency tuning and contrast sensitivity of single neurons
      in area 21a of the cat.
AB  - The spatial and temporal selectivities of single neurons in area 21a of the adult
      cat were investigated using sinusoidal gratings. Optimal spatial frequencies and
      visual acuity (high cut-off frequency) were fairly low and spatial bandwidth was
      mainly narrow. Contrast threshold was generally low but a substantial number of
      cells were only excited by high contrast stimuli. The temporal selectivity
      suggests that cells responded to a wide range of temporal frequencies.

PMID- 8738244
TI  - Estrogen increases the bradycardia elicited by central administration of the
      serotonin1A agonist 8-OH-DPAT in conscious rats.
AB  - Studies determined if estradiol modulates cardiovascular responses evoked by
      administration of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT1A
      receptor agonist, into the lateral cerebral ventricle. 8-OH-DPAT (100 nmol)
      produced equivalent decreases in blood pressure in male and ovariectomized female
      (OVX) rats with or without estradiol replacement. By contrast, the bradycardia
      elicited by 8-OH-DPAT (3-100 nmol) was greatest in OVX rats with estradiol.
      Estradiol did not alter the bradycardia produced by electrical stimulation of the
      vagus nerve. In summary, estradiol selectively enhanced the bradycardia elicited
      by 8-OH-DPAT suggesting that estrogen modulates the function of central 5-HT1A
      receptors regulating heart rate.

PMID- 8738245
TI  - Distribution of AMPA receptor subunits in the nucleus basalis of Meynert in aged
      humans: implications for selective neuronal degeneration.
AB  - Immunocytochemical techniques using polyclonal antibodies directed against GluR1
      and GluR2/3 subunits of the AMPA-selective receptor complex were used to examine
      the distribution of these receptor subunits within the nucleus basalis of Meynert
      (NBM) of non-demented elderly humans. Both somata and processes of magnocellular
      neurons within the NBM were intensely immunoreactive to GluR1 antibodies. In
      contrast, within the same region GluR2/3 immunolabeling was largely absent,
      although GluR2/3-positive neurons were abundantly distributed within adjacent
      brain regions (i.e., amygdala, entorhinal cortex and hippocampus). These data
      suggest that NBM neurons may be unique compared to those of other brain regions,
      in their response to glutamatergic excitation as mediated via non-NMDA receptors
      and be particularly vulnerable to glutamate excitotoxicity via a mechanism
      involving the destabilization of intracellular calcium.

PMID- 8738246
TI  - Changes of neurocalcin, a calcium-binding protein, in the brain of patients with
      Alzheimer's disease.
AB  - We assessed the amount of neurocalcin, a calcium-binding protein, in samples from
      the postmortem normal human and Alzheimer's disease (AD) brains using a specific
      antibody. In the AD brains, the amount of neurocalcin in the temporal cortical
      tissues was significantly lower than that in the controls. Neurocalcin was
      detected immunohistochemically mainly in the neuropil in the temporal cortex, and
      its localization was very similar to that of synaptophysin. These findings
      suggest that reduced levels of neurocalcin reflect a biochemical deficit related
      to the synaptic degeneration in AD.

PMID- 8738247
TI  - Effects of LY231617 and angiotensin IV on ischemia-induced deficits in circular
      water maze and passive avoidance performance in rats.
AB  - The antioxidant LY231617 has previously been shown to offer significant
      protection against postischemic cell death in the hippocampus and corpus striatum
      of rats. The present results extend this observation by demonstrating a
      concomitant protection against the spatial memory deficits that accompany damage
      to the hippocampus, as measured by the circular water maze task. These animals
      were further tested for changes in associative memory by employing a passive
      avoidance conditioning task. No deficits in passive avoidance conditioning were
      measured among the 4-vessel occlusion animals treated with LY231617 or vehicle.
      However, the intracerebroventricular injection of angiotensin IV (Ang IV)
      immediately prior to foot-shock conditioning improved retention of the
      conditioned response during the subsequent 2-day period. These results suggest
      that LY231617 can offer considerable protection against global ischemia-induced
      cell death in the hippocampus with resulting preservation of spatial memory
      abilities. In addition, untreated animals that suffered cell losses in the
      hippocampus remained capable of responding to the facilitory effect of centrally
      administered Ang IV on a non-spatial memory task. The hypothesized mechanisms of
      the protection characteristics of LY231617, and the nootropic effect of Ang IV,
      are discussed.

PMID- 8738248
TI  - Medial septal benzodiazepine receptors modulate hippocampal evoked responses and
      long-term potentiation.
AB  - Infusion of benzodiazepine (BDZ) receptor ligands into the medial septum (MS)
      produces a bidirectional modulation of spatial memory retention. The present
      experiments sought to determine the effects of BDZ ligands upon synaptic
      responses and long-term potentiation (LTP) in the dentate gyrus following
      electrical stimulation of the angular bundle. Intraseptal infusion of the BDZ
      agonist, chlordiazepoxide, decreased the amplitude of the evoked population spike
      and increased paired-pulse facilitation at a 150-ms interstimulus interval (ISI)
      in a dose-dependent manner. Intraseptal infusion of the BDZ antagonist,
      flumazenil (10 nmol), enhanced the amplitude of the dentate population spike and
      also increased paired-pulse facilitation at the 150-ms ISI. There was no effect
      of either BDZ receptor ligand upon the slope of the rising phase of the evoked
      population excitatory postsynaptic potential (pEPSP). Intraseptal flumazenil also
      significantly enhanced the magnitude of dentate LTP induced by high-frequency
      stimulation of the angular bundle. Intraseptal chlordiazepoxide failed to alter
      LTP induction. These results indicate that intraseptal infusion of an amnestic
      dose of the BDZ ligand, chlordiazepoxide, decreases the excitatory responsiveness
      of the dentate gyrus to its synaptic input from entorhinal cortex. In contrast,
      the promnestic BDZ ligand, flumazenil, enhances dentate granule cell
      responsivity, and facilitates synaptic plasticity in the dentate gyrus network.
      Taken together these data suggest that the memory impairing and memory enhancing
      action of these compounds may be a function of their ability to alter hippocampal
      physiology during a critical phase of memory. The potential role of septodentate
      cholinergic and GABAergic projections in the present observation is discussed.

PMID- 8738249
TI  - Cerebroprotective effect of stable nitroxide radicals in closed head injury in
      the rat.
AB  - Nitroxide stable radicals are unreactive toward most diamagnetic molecules, but
      readily undergo one-electron redox reactions with paramagnetic species such as
      free radicals and transition metals, thus serving as cell permeable antioxidants.
      The involvement of reactive oxygen species in the pathophysiology of neurotrauma
      has been well established. The neuroprotective properties of three nitroxides:
      2,2,6,6-tetramethylpiperidine-1-N-oxyl (TPO), the hydrophilic analog: TPL, and
      its reduced form: TPH, were tested in a rat model of closed head injury (CHI).
      CHI was induced in ether anesthetized rats by a weight drop device and recovery
      was followed for up to 24 h. The "clinical status' was evaluated according to a
      "Neurological Severity Score' (NSS), at 1 h and 24 h, the difference between
      these scores, delta NSS, reflecting the extent of recovery. Edema was assessed by
      measurement of water content at 24 h. The integrity of the blood-brain barrier
      (BBB) was investigated using Evans Blue extravasation. TPL, TPH and TPO
      facilitated clinical recovery, the latter causing a more pronounced effect (delta
      NSS = 7.63 +/- 0.26 in treated rats vs 4.94 +/- 0.48 in control rats, P < 0.001).
      TPL was found to significantly reduce edema formation (80.13% +/- 0.26 vs 83.65%
      +/- 0.49, P < 0.001) and to ameliorate BBB disruption (P < 0.001). The
      therapeutic window of TPL was found to be in the range of 4 h after CHI. The
      mechanisms underlying the nitroxide neuroprotective activity presumably involve:
      (a) reoxidation of reduced transition metal ions; (b) a selective radical-radical
      reaction; and (c) catalytic removal of intracellular and extracellular .O2-. The
      results indicate that nitroxides could be used in neuroprotective treatment of
      CHI.

PMID- 8738250
TI  - Effects of ciliary neurotrophic factor on retrograde cell reaction after facial
      nerve crush in young adult rats.
AB  - Locally applied ciliary neurotrophic factor (CNTF) has a powerful effect on
      retrograde axonal reaction following facial nerve crush in neonatal rats. We
      examined whether it also exerts a strong effect on retrograde axonal reaction in
      young adult rats when administered subcutaneously. The dose was 1 mg/kg body
      weight, three times a week, similar to that used in a previous experiment in
      which CNTF was reported to have an effect. We studied changes in the morphology
      of the motor nerve cell bodies, in the number of perineuronal microglial cells
      and in the expression of five proteins. It appeared that CNTF prevented swelling
      of the facial motoneuron cell bodies but it did not influence the swelling of the
      nucleus nor the shift of the nucleus towards the periphery. In saline-treated
      rats, facial nerve crush resulted from day two to day six in a marked increase in
      the number of perineuronal glial cells. This increase was neither diminished nor
      augmented by CNTF. Following facial nerve crush, the immunoreactivity of the
      proteins C3bi, GFAP, B-50 and CGRP increased in the glial cells and motoneuron
      cell bodies, whilst the immunoreactivity of synaptophysin at the membrane of the
      motoneuron cell bodies decreased. CNTF had no obvious effect on these changes. It
      was concluded that in young adult rats under the present conditions, CNTF had
      only a small effect on a specific aspect of the retrograde cell reaction. The
      small effects might be explained by the minor availability of CNTF to the
      motoneuron cell bodies. The gain in body weight of rats treated with CNTF was
      less than that of saline-treated rats.

PMID- 8738251
TI  - Role of the alpha 1-, and alpha 2- and beta-adrenoceptors of the median preoptic
      area on the water intake, renal excretion, and arterial pressure induced by ANG
      II.
AB  - The present experiments were conducted to investigate the role of the alpha 1-,
      alpha 2- and beta-adrenergic receptors of the median preoptic area (MnPO) on the
      water intake and urinary electrolyte excretion, elicited by central injections of
      angiotensin II (ANG II). Prazosin (an alpha 1-adrenergic receptor antagonist) and
      yohimbine (an alpha 2-adrenergic receptor antagonist) antagonized the water
      ingestion, Na+, K+, and urine excretion induced by ANG II. Administration of
      propranolol, a beta-adrenergic receptor antagonist increased the Na+, K+, and
      urine excretion induced by ANG II. Previous treatment with prazosin and yohimbine
      reduced the pressor responses to ANG II. These results suggest that the
      adrenergic neurotransmission in the MnPO may actively participate in ANG II
      induced dipsogenesis, natriuresis, kaliuresis, diuresis and pressor responses in
      a process that involves alpha 1-, alpha 2-, and beta-adrenoceptors.

PMID- 8738252
TI  - Clenbuterol protects mouse cerebral cortex and rat hippocampus from ischemic
      damage and attenuates glutamate neurotoxicity in cultured hippocampal neurons by
      induction of NGF.
AB  - It has been shown previously that clenbuterol, a beta 2-adrenergic receptor
      agonist, enhances NGF synthesis in adult rat brain. Since NGF is able to protect
      neurons against damage, we tried to find out whether clenbuterol can rescue
      cultured hippocampal neurons from excitotoxic damage by induction of NGF. The
      neuroprotective activity of clenbuterol on neurons in the vulnerable CA1 subfield
      of the hippocampus was tested in a rat model of transient forebrain ischemia.
      Additionally, in the mouse model of focal cerebral ischemia the ability of
      clenbuterol to reduce the infarct size was examined. Exposure of mixed
      neuronal/glial hippocampal cultures to clenbuterol (1 to 100 microM) enhanced
      significantly the content of NGF measured in the culture medium by two-site
      ELISA. The excitotoxic injury was induced in the same type of cells after 14 days
      in vitro by exposure to 1 mM L-glutamate for 1 h in serum-free medium. NGF itself
      (0.15 to 100 ng/ml) added to the growth medium 4 h before until 18 h after
      induction of injury (the point of glutamate-toxicity measurement), protected
      hippocampal neurons from excitotoxic damage. Clenbuterol (1 to 100 microM)
      provided similar neuroprotection as NGF under the same experimental conditions.
      The neuroprotective activity of clenbuterol (100 microM) against glutamate
      induced damage in hippocampal cultures was blocked by anti-NGF monoclonal
      antibodies (0.5 microgram/ml) added to the medium during the clenbuterol
      exposure, demonstrating that the neuronal rescue is mediated by NGF. Propranolol,
      a beta-adrenergic receptor antagonist (10 microM) added 20 min before and kept in
      the medium during exposure of the cultures to clenbuterol (1 microM) reversed the
      neuroprotective activity, suggesting that the induction of NGF and
      neuroprotection caused by clenbuterol are mediated via beta-adrenergic receptor
      activation. The capacity of clenbuterol to protect hippocampal neurons was also
      demonstrated in vivo in a rat model of transient forebrain ischemia. Clenbuterol
      (4 x 1 mg/kg) administered intraperitoneally increased the number of viable
      neurons in CA1 subfield of the rat hippocampus. Furthermore, clenbuterol (0.3 and
      1 mg/kg, i.p. and 1 mg/kg, s.c.) reduced significantly the infarct area on the
      mouse brain surface after occlusion of the middle cerebral artery. The present
      data demonstrate that clenbuterol induces NGF synthesis in cultured hippocampal
      cells and protects hippocampal neurons from excitotoxic damage. The
      neuroprotective activity of clenbuterol is also demonstrated in vivo in two
      rodent models of cerebral ischemia. The results offer strong evidence that the
      neuroprotective activity of clenbuterol is caused by activation of beta
      adrenergic receptors and the subsequent increased expression of NGF.

PMID- 8738253
TI  - Effect of fasting and immobilization stress on estrogen receptor immunoreactivity
      in the brain in ovariectomized female rats.
AB  - The present study examined the effect of 48-h fasting and 1-h immobilization on
      estrogen receptor immunoreactivity in selected hypothalamic areas and the nucleus
      of the solitary tract (NTS) in ovariectomized rats. Fasting induced an increase
      in ER-immunoreactive cells in the paraventricular nucleus (PVN), periventricular
      nucleus (PeVN) and NTS compared with the unfasted control group. Similarly,
      immobilization caused an increase in ER-positive cells in the same areas, PVN,
      PeVN and NTS, versus the non-immobilized group. There was no significant increase
      in the number of ER-immunoreactive cells in the preoptic area (POA), arcuate
      nucleus (ARC) or ventromedial hypothalamic nucleus (VMH) following fasting and
      immobilization. Our previous work in ovariectomized rats with estrogen
      microimplants in the brain revealed that the PVN and A2 region of the NTS are the
      feedback sites of estrogen in activating the neural pathway to suppress pulsatile
      LH secretion during 48-h fasting. The result in the food-deprived rats suggests
      that estrogen modulation of the suppression of LH secretion during fasting is
      partly due to the increase in estrogen receptors in the PVN and A2 region. The
      physiological significance of the increase in neural ER following immobilization
      remains to be elucidated.

PMID- 8738254
TI  - Changes in nociceptive reflex facilitation during carrageenan-induced arthritis.
AB  - Facilitation of neuronal responses induced by repetitive electrical stimulation
      of C-fibres (wind-up) is thought to be a substrate of hyperalgesia. There is
      little information on how these responses are in turn modified during
      hyperalgesia, and the extent to which hyperalgesic states also induce a
      facilitation of the neuronal responses mediated by A-fibres. The current study
      was undertaken in order to evaluate the effects of peripheral inflammation and
      stimulus presentation on the facilitation of nociceptive reflexes. Flexor
      reflexes, recorded as single motor units, were evoked in rats by cycles of low
      and high frequency electrical stimulation with pulse durations of 0.2, 0.5 and 2
      ms. Responses were studied in control and inflammatory conditions, using the
      carrageenan-induced mono-arthritis model. The results show that the facilitation
      of late (C-fibre mediated) responses was proportional to the pulse duration of
      stimulation, as well as to the stimulation frequency. Facilitation was always
      higher when animals were subjected to inflammation. In inflammatory conditions,
      facilitation of reflexes was observed not only for late (C-fibre mediated) but
      also for early (A-fibre mediated) reflex responses. However, the facilitation of
      these early responses was not proportional to the intensity of stimulation. Thus,
      in arthritic animals, late (C-fibre mediated) flexion reflexes elicited from the
      skin, are facilitated and early (A-fibre mediated) reflexes are not only
      facilitated but, in addition, show a novel wind-up phenomenon.

PMID- 8738256
TI  - Synaptic inhibition mediated by GABAB receptors in the neonatal rat spinal cord
      in vitro.
AB  - In the neonatal rat spinal cord in vitro prolonged inhibition of dorsal root to
      ventral root reflexes was achieved by electrical stimulation of an adjacent
      ipsilateral dorsal root. This prolonged inhibition lasted in excess of 1 s. An
      early phase of the prolonged inhibition was reduced by the GABAA receptor
      antagonist bicuculline methochloride with a concomitant reduction of dorsal root
      potentials which are an indication of primary afferent depolarisation. A longer
      latency and duration component of prolonged inhibition could be blocked by the
      selective GABAB receptor antagonist CGP56999A and therefore appeared to be
      mediated by baclofen-sensitive GABAB receptors. This GABAB receptor antagonist
      did not reduce dorsal root potentials suggesting that the component of prolonged
      inhibition mediated by GABAB receptors did not involve primary afferent
      depolarisation.

PMID- 8738255
TI  - Ionic basis of the membrane potential responses of rat dorsal vagal motoneurones
      to HEPES buffer.
AB  - The effects of 10 mM HEPES (N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid)
      buffered artificial cerebrospinal fluid (aCSF) on membrane potential and the
      action potential were studied in 93 dorsal vagal motoneurones (DVMs) using an in
      vitro slice preparation of the rat medulla. Changing from bicarbonate/CO2 aCSF to
      HEPES aCSF resulted in a depolarisation of 6.0 +/- 0.6 mV and an increase in
      input resistance (RIn; n = 61). In the presence of 5 mM 4-AP, HEPES either had
      little effect (n = 9) or hyperpolarised the membrane (n = 10). Mn2+ (3 mM) or
      Ni2+ (200 microM) abolished the hyperpolarisation and its associated increase in
      RIn. In voltage-clamp studies 5 mM 4-AP eliminated a transient outward current
      and Ni2+ blocked an inactivating inward current. It is concluded that HEPES
      buffer reduces the contribution of the A current to resting membrane potential
      and also reduces a Ni(2+)-sensitive transient ICa.

PMID- 8738257
TI  - Effects of intravenous phenylephrine on blood pressure, nociception, and neural
      activity in the rostral ventral medulla in rats.
AB  - Acute or chronic increases in arterial blood pressure are associated with
      decreases in nociception. In addition, acute increases in arterial blood pressure
      inhibit ON cells and excite OFF cells of the rostral ventral medulla (RVM). The
      current study tested whether the antinociception produced by increases in blood
      pressure is dependent on changes in the activity of ON and/or OFF cells. Single
      unit activity of ON or OFF cells was recorded in the RVM during increases in
      blood pressure produced by intravenous infusion of phenylephrine (1, 2.5, or 10
      micrograms/min for 21 min) in lightly anesthetized rats. Nociception was measured
      using the tail flick test. Phenylephrine dose-dependently increased mean arterial
      pressure and tail flick latency, but had inconsistent effects on neural activity
      in the RVM. In a second study, the effects of phenylephrine infusion on tail
      flick latency was determined before and after saline or lidocaine microinjections
      into the RVM. Lidocaine had no effect on the ability of phenylephrine to inhibit
      the tail flick reflex. These data suggest that the RVM, and therefore ON and OFF
      cells, is not required for phenylephrine-induced antinociception.

PMID- 8738258
TI  - Peripheral-type benzodiazepine receptors in association with epileptic seizures
      in EL mice.
AB  - Peripheral-type benzodiazepine receptors (PBR) in the brain were studied in
      association with epileptic seizures using EL mice, an animal model of epilepsy,
      and DDY mice as controls. Ro 5-4864 (i.p.), a specific agonist for PBR, elicited
      tonic-clonic convulsions in EL mice 2.6-times more potently than in DDY mice with
      CD50s of 11.9 and 31.2 mg/kg for EL and DDY mice, respectively. In contrast,
      pentylenetetrazole (i.p.) exerted convulsant actions on EL and DDY mice in a less
      differential way with CD50s of 29.2 and 48.1 mg/kg for EL and DDY mice,
      respectively. PK 11195 (i.v.), a specific antagonist for PBR, raised seizure
      thresholds of EL mice at a dose of 2 mg/kg. Binding assay revealed a 50% higher
      density of [3H]Ro 5-4864 binding sites in the mitochondrial fraction isolated
      from the cerebrum of EL mice in comparison with DDY mice. Similarly, a 40% higher
      density of [3H]flunitrazepam binding was observed in the mitochondrial fraction
      of EL mice. The results support the hypothesis that PBR, particularly those
      associated with mitochondria, are involved in the pathogenesis of epileptic
      seizures in EL mice.

PMID- 8738259
TI  - Quantitative solubilization and analysis of insoluble paired helical filaments
      from Alzheimer disease.
AB  - In this study, we evaluate the ability of several solvents to solubilize
      insoluble paired helical filaments (PHF) of Alzheimer disease. Specifically, we
      use protein extraction and reduction in the volume of insoluble material as
      quantitative assays to establish solvents of PHF. Using sequential categories of
      protein solvent to analyze insoluble PHF, only alkali or exhaustive proteolysis
      are effective in completely solubilizing PHF, while a variety of denaturants are
      ineffective. Alkali does not affect the phosphorylation state of PHF and complete
      dephosphorylation of PHF with hydrofluoric acid does not affect PHF solubility.
      These findings suggest that the 'hyperphosphorylation' of PHF proteins is not
      responsible for PHF insolubility. However the in vitro glycation of tau generates
      PHF that are insoluble in SDS and soluble in alkali. These findings suggest that
      protein crosslinks, including advanced glycation endproduct-derived crosslinks
      which were recently described in Alzheimer disease, play a major role in
      effecting PHF insolubility in vivo.

PMID- 8738260
TI  - Deferoxamine improves spatial memory performance following experimental brain
      injury in rats.
AB  - Traumatic brain injury (TBI) causes impairments of both motor and spatial memory
      performances. Research is only beginning to reveal the biochemical mechanism(s)
      underlying these deficits. It has been postulated that reactive oxygen species
      such as the superoxide and hydroxyl radicals, as well as the peroxynitrite anion,
      are generated by injury and may play a critical role in the observed memory
      deficits. The highly reactive hydroxyl radical, which is thought to contribute to
      neuronal toxicity, can be generated by an iron-catalyzed reaction. The source of
      this iron (or iron-bound proteins) could be a compromise of the blood-brain
      barrier, which can occur following TBI. In this report, we investigate the
      ability of deferoxamine, a scavenger of free iron, the hydroxyl radical and the
      peroxynitrite anion, to facilitate behavioral recovery following a controlled
      cortical impact of rats. Intraperitoneal administration of this drug prior to the
      injury did not affect the rate of recovery from motor deficits in comparison to
      vehicle (saline)-injected animals. However, deferoxamine-treated animals showed
      significant improvement in spatial memory performance in a Morris water maze
      task. Volumetric analysis of cortical tissue loss showed no significant
      differences between vehicle- and drug-injected animals. Similarly, histological
      examination of the hippocampus did not reveal any gross differences between the
      two groups. These results indicate that deferoxamine improves spatial memory
      performance, possibly through protection from neuronal dysfunction.

PMID- 8738261
TI  - 3,3'-Iminodipropionitrile induces neurofilament accumulations in the perikarya of
      rat vestibular ganglion neurons.
AB  - Exposure of rats to 3,3'-iminodipropionitrile (IDPN) results in neurofilament
      (NF)-filled swellings in the proximal axons of a number of large neurons,
      including sensory neurons in the dorsal root ganglia (DRG) and motor neurons in
      the spinal cord. The present report describes the effects of acute and chronic
      IDPN exposure on the vestibular ganglion (VG) neurons as compared to those on the
      DRG neurons. In the VG, IDPN induced intra-perikaryal accumulation of
      morphologically and immunocytochemically identified NFs. In the DRG of the same
      treated animals, IDPN induced proximal axonal swelling but no perikaryal NF
      accumulations. We concluded that the VG neurons preferentially express the IDPN
      induced NF pathology in their myelinated cell bodies. It is hypothesized that the
      NF pathology occurring after IDPN is preferentially expressed in myelinated
      structures.

PMID- 8738262
TI  - Distribution of c-Fos in guinea-pig brain following morphine withdrawal.
AB  - The distribution of the immediate-early gene and transcription factor protein, c
      Fos, was examined in the brains of guinea-pigs following treatment with morphine,
      naloxone or naltrexone, or the induction of morphine withdrawal by these opioid
      antagonists. Guinea-pigs were given subcutaneous injections of morphine sulphate
      or tartrate three times per day in increasing doses for three days (total dose
      690 mg/kg as base). Control animals received saline injections. Naloxone
      hydrochloride (30 mg/kg), naltrexone hydrochloride (15 mg/kg) or saline was
      administered subcutaneously 1 h after the last dose of morphine or saline, and
      the animals killed 1.5 h later by perfusion-fixation under deep sodium
      pentobarbitone anaesthesia. In the animals that were treated with morphine and
      withdrawn with either naloxone or naltrexone, c-Fos was expressed in neurons in
      many brain areas, including the frontal and cingulate cortices, olfactory
      tubercles, ventral pallidum, nucleus accumbens, habenular, paraventricular
      thalamic nucleus, septal and arcuate nuclei, lateral and posterior hypothalamic
      areas, ventral tegmental area, central grey, dorsal raphe nucleus, locus
      coeruleus, raphe magnus, lateral paragigantocellular nucleus and solitary tract
      nucleus. In contrast, only low levels of c-Fos were found in brains of animals
      that had been treated for three days with morphine followed by saline, or with
      saline followed by naltrexone or naloxone. The widespread distribution of c-Fos
      induced by morphine withdrawal reflects the complexity of the accompanying
      behavioural and autonomic responses.

PMID- 8738263
TI  - Polyamine amides are neuroprotective in cerebellar granule cell cultures
      challenged with excitatory amino acids.
AB  - Primary cultures of rat cerebellar granule cells have been used to assess the
      potential neuroprotective effects of philanthotoxins and argiotoxin-636 (ArgTX
      636). These polyamine amides are potent antagonists of ionotropic L-glutamate (L
      Glu) receptors. In granule cells loaded with fluo-3, ArgTX-636 and philanthotoxin
      343 (PhTX-343) antagonised increases of intracellular free calcium concentration
      ([Ca2+]i) that were stimulated by N-methyl-D-aspartate (NMDA). The antagonism was
      use-dependent. Antagonism by PhTX-343 was fully reversible, but recovery
      following antagonism by ArgTX-636 was slow and only partial during the time
      course of an experiment. Neither compound inhibited K(+)-induced increases in
      [Ca2+]i. In excitotoxicity studies with cerebellar granule cells, the release of
      lactate dehydrogenase (LDH) and morphological observations were used to assess
      cell death. A 20-30 min exposure to 500 microM NMDA, 100 microM L-Glu or 500
      microM kainate was sufficient to kill > 90% of the cells after 18-20 h. When
      added 5 min prior to, and during agonist exposure, PhTX-343 and ArgTX-636
      provided total neuroprotection. ArgTX-636 was about 20-30 fold more potent than
      PhTX-343 against NMDA, but was approximately equipotent with PhTX-343 against a
      kainate challenge. Neither of the toxins showed any inherent toxicity even at 400
      microM and 100 microM respectively. Some analogues of PhTX-343 are more potent,
      both in terms of antagonism of NMDA-stimulated increases of [Ca2+]i and
      neuroprotection, than PhTX-343 and ArgTX-636.

PMID- 8738264
TI  - Repeated seizures increase GFAP and vimentin in the hippocampus.
AB  - Reactive gliosis is a response of astrocytes to a variety of insults that is
      characterized by hypertrophy of the cell bodies and processes and an increase in
      the expression of glial fibrillary acidic protein (GFAP). The signal that
      regulates the transition to the reactive state and the role of vimentin in
      reactive gliosis are unknown. The experiments here used a model of repeated
      seizures in the hippocampal-parahippocampal circuits to determine the extent and
      time course of reactive gliosis, including the appearance of vimentin, in
      response to seizures. Reactive gliosis, detected by immunohistochemistry for the
      presence of GFAP and vimentin, was present 2-7 days after the repeated seizures.
      At least 9 seizures, or at least 250 s of seizure discharge, were needed to
      induce reactive gliosis. After seizures, cells staining for vimentin were found
      in the dentate gyrus molecular layer and hilar region, as well as in the
      molecular layer of CA1. Fewer cells were stained in the CA3 region. These
      experiments demonstrate that repeated discrete seizures of the hippocampal
      parahippocampal circuits can cause reactive gliosis and localized induction of a
      glial protein (vimentin) that is not normally expressed in the adult brain.

PMID- 8738265
TI  - Daily rhythm of serum melatonin in patients with dementia of the degenerate type.
AB  - The daily rhythm in serum melatonin levels was measured in patients with dementia
      of the degenerate type (Alzheimer's disease, Pick's disease and senile dementia
      of the Alzheimer type) by radioimmunoassay. Thirteen patients (age: 69.0 +/- 8.0
      years, mean +/- S.D.) were studied. All patients were hospitalized at the time of
      the study and had a history of sleep-wake disturbances, nocturnal wandering
      and/or delirium. We also studied 13 age-matched healthy control subjects (control
      group 1), ten young adults (control group 2), and nine hospitalized patients
      without dementia (control group 3). Two subjects in the control groups showed no
      measurable changes in melatonin level throughout the day, while the other 30
      control subjects exhibited a clear daily rhythm with the peak concentration
      occurring during the night. On the other hand, four out of the 13 patients with
      dementia did not show any melatonin rhythm. Two of the demented patients who did
      not exhibit melatonin rhythm displayed clinical symptoms of rhythm disorders. One
      out of the nine patients with melatonin rhythm presented with clinical symptoms,
      such as delirium and sleep-wake disturbance. Our results suggest that the
      probability of absent melatonin rhythm is higher in demented patients compared
      with subjects without dementia. However, a lack of melatonin rhythm is not always
      associated with symptomatic rhythm disorders. Since the melatonin rhythm reflects
      that of the suprachiasmatic nucleus, it follows that the SCN function of the
      patients having a history of rhythm disorders was not always severely damaged.

PMID- 8738266
TI  - Peripherally obtained electrophysiological responses to olfactory stimulation in
      man: electro-olfactograms exhibit a smaller degree of desensitization compared
      with subjective intensity estimates.
AB  - After chemical stimulation of the human olfactory epithelium it is possible to
      record a negative response (electro-olfactogram, EOG) which is interpreted as the
      summated receptor potentials of the olfactory nerve. The aim of the present
      investigation was to test the EOG's changes in relation to pairs of stimuli.
      Stimulation was performed with vanillin (0.8 ppm) regarded to exclusively excite
      fibers of the olfactory nerve. Ten healthy volunteers participated in the
      experiments. Pairs of stimuli were applied at different interstimulus intervals
      ISIs (2-8 s). EOG could be recorded in 6 out of 10 subjects. After olfactory
      stimulation the responses' peak amplitude was found to range from 0.15 to 1.8 mV.
      When pairs of olfactory stimuli were applied responses obtained at an ISI of 8 s
      were clearly separated whereas at an ISI of 2 s responses were superimposed on
      each other. As with an ISI of 8 s, the amplitude produced by the second stimulus
      was nearly as great as the first responses' amplitude (decrease by approximately
      20%). In contrast, intensity estimates obtained in an additional experiment (n =
      10) decreased by 40-60%. Based on the present data peripheral encoding in the
      olfactory system appears to be less subject to desensitization compared to the
      decrease of intensity estimates.

PMID- 8738267
TI  - Water escape performance of adult RCS dystrophic and congenic rats: a functional
      and histomorphometric study.
AB  - The dystrophic Royal College of Surgeons (RCS) rat undergoes photoreceptor
      degeneration due to a hereditary defect in the retinal pigment epithelium. The
      congenic rat remains unaffected. Although the retinal degeneration is well
      characterized, few functional studies of this strain are available. We wished to
      compare the visual function of congenic and dystrophic RCS rats using a water
      escape paradigm that tested their ability to find a submersed, randomly placed
      platform using a light source as a clue. Three different behavioral experiments
      were sequentially performed on all animals: Experiment 1--The Light and Platform
      test measured the time to swim from the center of the pool to a platform located
      under a light clue. Each animal was given 10 trials. Experiment 2--The No Light
      with Platform test was performed as above except no light clue was used.
      Experiment 3--The Light and No Platform test was performed with a light clue but
      without a platform. The animal was allowed to swim for 2 min. All trials were
      videotaped. After the final experiment, the animals were sacrificed and a
      histomorphometric analysis of their retinas were performed. Expt. 1--The time to
      find the platform using light as a clue was greater for the dystrophic than for
      the congenic rats. Expt. 2--In the absence of light clue, there was no
      significant difference in performance between the congenic and dystrophic
      animals. Expt. 3--In the absence of a platform, a significantly greater amount of
      time was spent in the area indicated by the light clue by the congenic animals as
      compared to the dystrophic. Morphometric analysis revealed a mean number of 133
      photoreceptor nuclear profiles/90 microns of retina for congenic rats as compared
      to 0.14 for dystrophic rats. This simplified version of the Morris water maze
      permits quantitative evaluation of visually-guided behavior in an important model
      of retinal degeneration.

PMID- 8738268
TI  - Elevated connexin43 immunoreactivity at sites of amyloid plaques in Alzheimer's
      disease.
AB  - The distribution of the astrocytic gap junctional protein, connexin43 (Cx43) was
      compared immunohistochemically with that of amyloid plaques in Alzheimer's
      Disease (AD) brain. By light microscopy, cortical areas containing numerous
      beta/A4 amyloid plaques exhibited increased immunostaining density for Cx43 and
      some plaques corresponded exactly to sites of intensified Cx43 immunoreactivity.
      By electron microscopy, Cx43 was localized to astrocytic gap junctions in AD
      brain. Increased Cx43 expression in AD may represent an attempt to maintain
      tissue homeostasis by augmented intercellular communication via gap junction
      formation between astrocytic processes that invest senile plaques, or
      alternatively, an aberrant induction of astrocytic Cx43 expression which may
      further compromise homeostasis and exacerbate pathological conditions in the
      microenvironment of amyloid plaques.

PMID- 8738269
TI  - Thymulin reduces hyperalgesia induced by peripheral endotoxin injection in rats
      and mice.
AB  - In a new model of peripheral localized inflammation, induced by intraplantar
      endotoxin (1.25 micrograms) injection in the hind paw of rats and mice, thymulin,
      a hormone of the thymus gland involved in immunomodulation, reduced inflammatory
      pain. High doses of thymulin reduced significantly, and in a dose-dependent
      manner, mechanical hyperalgesia as assessed by the paw pressure test and thermal
      hyperalgesia as assessed by the hot plate test and tail immersion test.

PMID- 8738270
TI  - alpha-Lipoic acid protects against reperfusion injury following cerebral ischemia
      in rats.
AB  - Ischemic-reperfusion injury in humans occurs in conditions such as stroke,
      cardiac arrest, subarachnoid hemorrhage or head trauma. Maximal tissue damage is
      observed during reperfusion, which is primarily attributed to oxidative injury
      resulting from production of oxygen free radicals. One of the major consequences
      of such damage is the depletion of the cellular antioxidant, glutathione (GSH)
      leading to oxidation of protein thiols to disulfides and the loss of activity of
      critical enzymes having active thiol group(s). Thus, the maintenance of thiol
      homeostasis is an important factor in cell survival. The effect of thiol
      antioxidants like alpha-lipoic acid and the isopropyl ester of GSH was examined
      on the morbidity and mortality of rats subjected to reperfusion following
      cerebral ischemia induced by bilateral carotid artery occlusion and hypotension.
      While the GSH isopropyl ester had no significant protective effect; after
      pretreatment of rats, alpha-lipoic acid was detected in the rat brain and it
      dramatically reduced the mortality rate from 78% to 26% during 24 h of
      reperfusion. The natural thiol antioxidant, alpha-lipoic acid is effective in
      improving survival and protecting the rat brain against reperfusion injury
      following cerebral ischemia.

PMID- 8738271
TI  - Satietin: Fos mapping of putative brain sites of action.
AB  - A purified extract of a blood-borne satiety factor, called satietin, was injected
      into the cerebral ventricles of rats that were either fed ad libitum or were food
      deprived. The animals were killed 2 h after injection and their brains
      subsequently sectioned and stained for Fos-like immunoreactivity (Fos-IR) to
      determine the putative sites of action for satietin in the brain. Fos-IR was
      induced in only a few locations, the most prominent sites being the bed nucleus
      of the stria terminalis, the central nucleus of the amygdala, and the
      parvocellular division of the paraventricular nucleus of the hypothalamus. Each
      of these areas has previously been implicated in the control of feeding behavior.
      Sites in the hindbrain that are associated with nausea were devoid of satietin
      induced Fos-IR. Finally, these sites of action of satietin show some differences
      from sites that are prominently activated by other classes of anorectic agents.

PMID- 8738272
TI  - Oxidative stress-resistant cells are protected against haloperidol toxicity.
AB  - The neuroleptic drug haloperidol is cytotoxic to cells of different origin in
      high doses. The mechanism of haloperidol toxicity may involve oxidative stress
      resulting in necrosis. In the present study, we show that rat pheochromocytoma
      PC12 cell clones which were selected for resistance to the toxicity of the
      oxidative stressor amyloid beta-protein (A beta), were also resistant to
      haloperidol toxicity. This data strongly supports the causative involvement of
      free radicals in haloperidol-induced cell death.

PMID- 8738273
TI  - Biphasic modulation of GABA release by nitric oxide in the hippocampus of freely
      moving rats in vivo.
AB  - The effect of altering hippocampal nitric oxide (NO) levels on basal and N-methyl
      D-aspartate receptor-evoked release of GABA has been studied in freely moving
      rats. N-Methyl-D-aspartate (NMDA) increased extracellular GABA in a concentration
      dependent manner. The nitric oxide synthase inhibitor L-nitro-arginine-methyl
      ester (L-NAME; 100 microM) increased basal GABA release, and also enhanced
      release of GABA evoked by NMDA (100 microM) compared with the same concentration
      of NMDA infused alone. 200 microM L-NAME increased basal dialysate GABA, but to a
      lesser extent than the 100 microM concentration of the drug, and the NMDA-induced
      release of GABA was decreased. 1.0 mM L-NAME significantly decreased basal
      extracellular GABA, while abolishing the NMDA-evoked release of the amino acid.
      The actions of L-NAME were not mimicked by its much less active isomer D-nitro
      arginine-methyl ester. The NO donor S-nitroso-N-acetylpenicillamine decreased
      dialysate GABA at a 500 microM concentration but increased the extracellular
      level of the transmitter when infused at 1.0 and 2.0 mM concentrations. These
      data suggest that NO may mediate both excitatory and inhibitory functions in
      vivo.

PMID- 8738274
TI  - Chronic and intra-amygdala administrations of the ACTH(4-9) analog ORG 2766
      modulate behavioral changes after manipulation of NMDA-receptor activity.
AB  - Microinjection of N-methyl-D-aspartic acid (NMDA, 300 ng/3 microliters) into the
      left lateral ventricle causes a substantial increase in locomotor activity which
      can be significantly reduced by a chronic pretreatment with the ACTH(4-9)
      analogue ORG 2766(1 microgram/0.5 ml saline, subcutaneous (s.c.) every day for 7
      days, last injection 24 h before the NMDA-injection). A single dose of ORG 2766
      (1 ng/1 microliter) injected into the left central amygdaloid nucleus 30 min
      before the NMDA-injection was equally effective in reducing the increase in
      locomotion. Furthermore it counteracted the predominance of contralateral turning
      induced by the NMDA-injection. The data give support for the idea that ORG 2766
      excerts its effects on behavior and neural recovery by modulating NMDA receptor
      activity in the brain.

PMID- 8738276
TI  - Species differentiation of lungworms (Dictyocaulidae) by polymerase chain
      reaction/restriction-fragment-length polymorphism of second internal transcribed
      spacers of ribosomal DNA.
AB  - The bovine lungworm Dictyocaulus viviparus is found in cattle and deer species
      (roe deer, fallow deer). Although a separate lungworm species (D. eckerti) from
      roe deer has been described, this description, based on minor morphological
      differences, is not generally accepted. The aim of the present study was to
      examine genetic differences among four lungworm species isolated from cattle,
      sheep, horses, and fallow deer. Ribosomal second internal transcribed spacers
      (ITS2) of individual worms of all species were amplified by polymerase chain
      reaction (PCR), and restriction-fragment-length polymorphisms were analyzed after
      digestion with five different restriction enzymes. After electrophoretic
      separation of the digested PCR products, all four lungworm species showed
      different banding patterns. Lungworms from cattle (D. viviparus) and those from
      fallow deer (D. eckerti) were genetically distinct. These results are consistent
      with the hypothesis that the taxonomic classification of D. eckerti as a separate
      species is correct.

PMID- 8738275
TI  - Production of interleukin 10 during malaria caused by lethal and nonlethal
      variants of Plasmodium yoelii yoelii.
AB  - We investigated the induction of T-helper cell subsets during the course of
      lethal or nonlethal bloodstage Plasmodium yoelii 17X infection in C57BL/6 mice,
      which are relatively susceptible to these intraerythrocytic parasites. C57BL/6
      mice infected with the nonlethal variant (PyNL) showed a moderate level of
      parasitemia and resolution of primary acute infection by week 4. Mice infected
      with the lethal variant (PyL) developed fulminating parasitemia and ultimately
      died. T-helper subset function was assessed during infection by determining the
      kinetics of in vitro production of the Th1-derived cytokine interferon-gamma (IFN
      gamma) and the Th2-derived cytokine interleukin 10 (IL-10) by means of bioassay
      and enzyme-linked immunosorbent assay (ELISA), respectively. Spleen cells
      obtained from mice infected with PyL within the 1st week of infection produced
      high levels of IL-10 and IFN-gamma in response to malaria antigen. IL-10 also
      appeared in sera from PyL-infected mice at the same time at which the in vitro IL
      10 response peaked. In contrast, spleen cells from mice infected with PyNL failed
      to produce IL-10 during the course of infection. CD4+ T-lymphocytes from mice
      infected with the lethal variant were a major source of IL-10, although non T
      cells were also involved in the production of IL-10 during this malaria
      infection. In addition, the initial burst of IL-10 in response to malaria
      antigens was seen concomitantly with the production of IFN-gamma within the 1st
      week of infection. These results indicate that both Th1 and Th2 subsets of T
      helper lymphocytes are activated during infection with the lethal variant of P.
      yoelii and support the contention of other investigators that a strong Th2
      response early in infection is associated with the lethal outcome of malaria.

PMID- 8738277
TI  - Sensitivity of a polymerase chain reaction-based assay to detect Onchocerca
      volvulus DNA in skin biopsies.
AB  - A polymerase chain reaction (PCR) of a 150-bp tandem repeat of Onchocerca
      volvulus (O-150) combined with Southern-blot hybridization to species-specific
      DNA probes was employed for DNA detection. O-150 was amplified from parasites
      originating from Uganda, Benin, Cameroon, Liberia, Ghana, Burkina Faso, Mali, and
      Zaire and was successfully hybridized to digoxigenin-labeled oligonucleotides. To
      investigate the sensitivity of the PCR, 2 skin biopsies were taken from each of
      227 persons from Uganda with proven O. volvulus infections but with low
      microfilaria (mf) densities due to ivermectin treatment. One biopsy was tested by
      PCR and the other was digested using collagenase to assess the total number of
      mf. The PCR revealed 76.2% of the samples to be positive, and the collagenase
      method showed that 78.9% were positive, indicating similar sensitivity for the
      two methods. It is probable that for both techniques the biopsy must contain at
      least one live mf or fragments of a dead mf. In this study, no free or
      circulating O. volvulus DNA could be detected in skin biopsies by PCR.

PMID- 8738278
TI  - Kinetics study of the localization and quantitation of target antigens of
      immunoglobulin a antibodies in acquired and congenital toxoplasmosis.
AB  - The cellular distribution (localization and quantitation) of the target
      parasite's antigens in the tachyzoite along the IgA kinetics was determined in
      the course of acquired toxoplasmosis and congenital toxoplasmosis. In the case of
      acquired toxoplasmosis, throughout the IgA kinetics a correlation was noted
      between the membrane and submembrane immunolabeling and the results of the
      immunocapture and enzyme-linked immunosorbent assay IgA (ELISA-A) tests. The
      rhoptries' immunolabeling remained higher. The immunolabeling evolution and the
      results of the immunology tests were not closely related to the treatment
      (Rovamycin). From the congenital toxoplasmosis cases it was observed that
      membrane immunolabeling correlated with the results of the serology tests and
      with the treatment (Fansidar). The rhoptry antigens were recognized throughout
      the IgA kinetics; even when the serology tests became negative, immunolabeling
      persisted. Rhoptries appeared as secretory organelles of antigens recognized
      during acute, chronic, and congenital stages of Toxoplasma infection.

PMID- 8738279
TI  - Genomic variation in Trypanosoma cruzi clonal cultures.
AB  - Spontaneous changes in restriction DNA profiles and pulsed-field gel
      electrophoresis (PFGE) patterns, along with a concomitant loss of infectivity,
      were observed in infective clones of Trypanosoma cruzi strain Y either following
      a number of passages during the exponential growth phase of after subcloning in
      liver infusion tryptone (LIT) medium using as the probe a genomic fragment of the
      parasite (pMYP16), indicating naturally occurring rearrangements of DNA
      sequences. No variation could be detected when the genomic DNA was probed with
      conserved T. cruzi tubulin and actin genes. There was no correlation between such
      rearrangements and the life-cycle forms of the parasites, since trypomastigote
      forms showed the same karyotype and hybridization patterns as did epimastigote
      forms. The variations observed could be reverted and infectivity, recovered after
      inoculation of the parasites in newborn mice.

PMID- 8738280
TI  - Investigations into the production and function of leukotrienes during
      histotropic development of Oesophagostomum dentatum.
AB  - The dynamics of production and excretion of leukotrienes by parasitic larvae of
      Oesophagostomum dentatum and their role for the development of the larvae were
      studied. Larvae were cultured in vitro to the fourth stage (L4). Leukotriene B4
      (LTB4) was detected in homogenates and in supernatant of larvae, with the
      homogenate-protein-based values steadily decreasing during development. The
      homogenate-protein-based values of peptidyl leukotrienes (pepLT) remained fairly
      stable in both homogenates and supernatants, whereas the wormcount-based pepLT
      values increased significantly. The addition of diethylcarbamazine (DEC) to the
      culture medium straight from the beginning of culturing (12.8 or 25.5 mmol/l)
      reversibly hampered growth and development to L4. Application of DEC at 12.8
      mmol/l beginning on day 13 of in vitro cultivation exerted no significant effect
      on further development to L4. LTB4 appeared to counteract the inhibition of
      development by DEC. The results of this study indicate that endogenous LTs
      participate in regulation of the growth and development of O. dentatum.

PMID- 8738281
TI  - Immunocytochemical localization of glutamate-like immunoreactivity within the
      nervous system of the cestode Mesocestoides corti and the trematode Fasciola
      hepatica.
AB  - The localization and distribution of glutamate-like immunoreactivity (IR) in the
      nervous system of both the cestode Mesocestoides corti and the trematode Fasciola
      hepatica has been determined by an indirect immunofluorescent technique, in
      conjunction with confocal scanning laser microscopy (CSLM). Immunostaining was
      widespread in the central (CNS) and peripheral (PNS) nervous systems of both
      species examined. In the CNS, IR was evident in nerve cells and fibres in the
      cerebral ganglia, the cerebral commissure and the dorsal, ventral and
      longitudinal nerve cords. In the peripheral nervous system (PNS) of M. corti, IR
      was apparent in nerve plexuses associated with the subtegmental musculature and
      the musculature associated with the anteriorly positioned suckers. In F.
      hepatica, IR was evident in the innervation of both the oral and the ventral
      suckers. In the reproductive system of F. hepatica, glutamate-IR was observed
      around the ootype/Mehlis' gland complex.

PMID- 8738282
TI  - Ultrastructure study of the intramolluscan stages of Meiogymnophallus minutus
      (digenea: gymnophallidae) in Scrobicularia plana (bivalvia) from Portugal.
AB  - The ultrastructure of the tegument of the sporocyst and contained cercariae of
      Meiogymnophallus minutus found in Scrobicularia plana collected in Ria de Aveiro
      estuary (Portugal) were studied by scanning (SEM) and transmission electron
      microscopy (TEM). TEM revealed microvilli extending from the surface of the
      sporocyst tegument that contributed to the lacetrimmed surface morphology
      observed by SEM. The cercarial surface was papilliform and covered densely with
      single-pointed tegumental spines. On TEM, besides the spines and several
      mitochondria, translucid and electrondense spherical secretory vesicles were
      evident in the matrix of the tegument but were not seen on the sporocyst
      tegument. Uniciliate sensory receptors found in the cercaria of M. minutus were
      examined under SEM and TEM. Structural differences between the oral and the
      ventral sucker were observed. On the lip of the ventral sucker, large and strong
      spines were arranged in concentric rows, and two groups of six sensory papillae
      were placed concentrically and equidistantly. The oral sucker, surrounded by a
      crown of dense and long microvilli, exhibited a ring of uniciliate sensory
      papillae and some tegumental spines along the lip. The surface morphology of the
      M. minutus cercaria is compared with that of other Gymnophallidae cercariae.

PMID- 8738283
TI  - Polyamine N-acetyltransferase in Leishmania amazonensis.
AB  - N-Acetyltransferase, which is suggested to be responsible for the production of
      N1-acetylspermidine in Leishmania amazonensis and to be involved in the process
      of inactivation and degradation of excessive polyamines, was partially purified
      and characterized. Among the substrates tested, sym-norspermidine, sym
      norspermine, and 1,3-diaminopropane had the highest reaction rates, but the
      naturally occurring polyamines spermine and spermidine were also acetylated at
      considerable rates, whereas putrescine was a poor substrate. The Michaelis
      constants (Km values) for spermine and spermidine were 0.66 and 3.3 mM,
      respectively. The Km value for acetylcoenzyme A (acetyl-CoA) was determined to be
      34 microM. CoA inhibited the reaction in a competitive manner; the inhibition
      constant was 5 microM. The enzyme showed an apparent relative molecular mass of
      35,000.

PMID- 8738284
TI  - Observations on the ultrastructure and viability of the cystic stage of
      Blastocystis hominis from human feces.
AB  - This report describes the ultrastructure and viability of cysts of Blastocystis
      hominis from feces of infected patients. The cysts were round to ovoid, measured
      2-5 microns in size, and contained a condensed cytoplasm that had vacuoles of
      varying sizes, four nuclei, and as many as six cristate mitochondria. The cell
      wall was rather electron-lucent. Surprisingly, chromatoid-like structures were
      found in the cytoplasm and nucleus of some of the cysts. These have not
      previously been reported in Blastocystis. The cysts can survive in water for up
      to 19 days at normal temperatures but are fragile at extreme temperatures and in
      common disinfectants.

PMID- 8738285
TI  - Irradiated larval vaccination and antibody responses evaluated in relation to the
      expression of immunity to Heligmosomoides polygyrus.
AB  - Infections induced in NIH mice by irradiated (300 Gy) larvae of Heligmosomoides
      polygyrus effectively stimulated immunity to challenge, whereas unirradiated
      larvae did not. Importantly, this difference was lost by the elimination of the
      adult worms arising from unirradiated sensitising infections by drug treatment
      prior to challenge. No difference in the level of parasite-specific serum and
      mucosal IgG, IgG1, IgG2a, or IgA was detected between immune mice sensitised
      either with drug-abbreviated unirradiated or irradiated larval infections and non
      immune mice receiving two superimposed unirradiated infections. An enzyme-linked
      immunosorbent assay (ELISA) and immunoblotting data suggested that parasite
      specific IgG1 was the predominant antibody class in both serum and intestinal
      perfusates. IgA exhibited differences in antigen specificity between the serum
      and the intestine. In serum, IgA responses were directed predominantly to L4
      somatic antigens, whereas at the mucosal surface they were biased towards L4
      excretory/secretory (ES) antigens. No correlation was found between the intensity
      of the serum or mucosal antibody responses and the mean worm burdens in groups of
      immune or non-immune mice. Moreover, no correlation was found between levels of
      parasite-specific serum or mucosal IgG, IgG1, IgG2a or IgA and the loss of worms
      in individual mice.

PMID- 8738287
TI  - Investigation of different ontogenetic stages of Raillietiella sp. (Pentastomida:
      Cephalobaenida). Structure of the foregut and considerations about the feeding
      process.
AB  - The foregut of Raillietiella sp. was investigated ultrastructurally in different
      ontogenetic stages: the embryo prior to hatching, the first-stage larva, the
      infective fourth-stage larva from the intermediate host, and juveniles and adults
      from the definitive host. As early as at the embryo stage the chitinous mouth
      armature is highly specialized. During postembryogenesis this structure is
      modified until it reaches its final shape in the juvenile. The most important
      changes occur during the period of development from the infective larva to the
      juvenile, which is related to the change from the intermediate to the definitive
      host; only stages inhabiting the definitive host can use their mouth as a suction
      pump. Therefore, only juveniles and adults are capable of sucking blood, whereas
      larvae are dependent on accessible liquid food. The remaining foregut represents
      a conveyor tube, growing in width toward the midgut. From the juvenile stage
      onward the transition to the midgut is formed as a cardiac valve.

PMID- 8738286
TI  - Immunogenicity of Leucocytozoon caulleryi sporozoites and their reactivity with
      specific immune sera.
AB  - The immunogenicity of Leucocytozoon caulleryi sporozoites for chickens and their
      reactivity in vitro with specific immune sera were studied. Almost all of the
      chickens that had been immunized with the sporozoite antigens survived the
      sporozoite challenge. The degree of parasitemia observed in the immunized
      chickens was significantly lower than that found in the nonimmunized chickens.
      Specific antibodies against sporozoites were tested by the circumsporozoite
      precipitation (CSP) reaction. Antibodies were demonstrated in the sera of
      chickens that had been immunized with the sporozoite antigens or chickens that
      had recovered from a primary infection with L. caulleryi sporozoites. When viable
      mature sporozoites were incubated in vitro with serum from immune chickens,
      agglutination and a long, thread-like precipitate at one end of the sporozoite
      could be seen within a few minutes under a phase-contrast microscope. The effects
      of specific immune serum on the infectivity of sporozoites were examined by the
      sporozoite neutralization activity (SNA) test. Sporozoites that had been
      incubated in vitro with serum from immune chickens lost their infectivity to
      chickens. The CSP reaction and the SNA test in L. caulleryi infection were stage-
      and species-specific.

PMID- 8738289
TI  - Egg laying in vitro of Echinostoma caproni (Trematoda) in nutritive and
      nonnutritive media.
AB  - Egg laying in vitro was studied in Echinostoma caproni adults placed in 10 ml of
      nutritive or nonnutritive media for 48 h in petri-dish cultures maintained at 37
      degrees C in an atmosphere containing 7.6% CO2. Maximal egg laying occurred
      within 24 h in the defined medium RPMI 1640. Egg laying was significantly greater
      in this medium than in McCoy's or Locke's solution. Eggs released into the RPMI
      medium were capable of producing miracidia that were infective to Biomphalaria
      glabrata snails. Fried and Huffman (1996) referred to a technique used to obtain
      eggs of Echinostoma caproni in the defined medium RPMI 1640, but details of the
      study were not given. No information is available on egg laying of echinostomes
      in vitro. Such information could contribute to a better understanding of egg
      release in digeneans and would also be helpful in the acquisition of eggs for
      biology and chemistry studies. Current techniques used to obtain echinostome eggs
      involve worm homogenization, teasing of eggs from the worms' uteri, or recovery
      of eggs from feces (see Idris and Fried 1996 for details). The purpose of this
      communication is to report on an efficient procedure for the acquisition of eggs
      of E. caproni after the placement of adult worms in the defined medium RPMI 1640.
      E. caproni adults were grown in ICR mice for either 17 (young worms) or 112 days
      (old worms) as described previously (Ursone and Fried 1995a). Worms were removed
      from the small intestines and rinsed rapidly in three changes of sterile Locke's
      solution containing penicillin (200 IU/ml) and streptomycin (200 micrograms/ml;
      Fried and Contos 1973). Worms were placed in culture media within 30 min of their
      removal from hosts. Nutritive media consisted of RPMI 1640 and McCoy's medium
      (Sigma, St. Louis, Mo.). Non-nutritive media consisted of Locke's or Locke's 1:1
      (Ursone and Fried 1995b). All media contained antibiotics as described above.

PMID- 8738288
TI  - In vitro biosynthesis and in vivo processing of the major microneme antigen of
      Sarcocystis muris cyst merozoites.
AB  - The cDNA clone pSM/1.6 encoding the 26.5-kDa precursor molecule of the 16/17-kDa
      microneme antigen of Sarcocystis muris cyst merozoites was expressed in a cell
      free translation/translocation system to study translocation of the protein
      across membranes. The antigen was found to be translocated across heterologous
      endoplasmic reticulum membranes. Translocation was accompanied by cleavage of a
      signal peptide to create a 23-kDa polypeptide that was completely protected from
      digestion with proteinase K. Pulse-chase analysis of [35S]-methionine-labeled S.
      muris cyst merozoites demonstrated that the 16/17-kDa antigen derived from a 23
      kDa precursor molecule and that its processing occurred at between a few minutes
      and 2 h after biosynthesis. This leads to the conclusion that the native
      microneme antigen is secreted from the parasite cell via the endoplasmic
      reticulum. Sorting into micronemes might occur during transition through a Golgi
      like structure, involving cleavage of the hydrophilic propeptide to create the
      mature 16/17-kDa protein.

PMID- 8738290
TI  - The effect of spiroarsoranes on Trypanosoma brucei brucei and T. b. rhodesiense.
AB  - Topical application and intraperitoneal administration of spiroarsoranes were
      carried out to cure central nervous system (CNS) trypanosomiasis in the chronic
      Trypanosoma brucei GVR 35 mouse model. Topical application appeared more
      efficient than intraperitoneal injection. The periods of aparasitaemia after
      treatment were longer but none of the mice was permanently cured. Combination
      treatment with eflornithine (DFMO) and the spiroarsoranes failed to show any
      synergistic effect. In addition, spiroarsorane I was evaluated against the T. b.
      rhodesiense KETRI 2634 strain, whereby 60-mg/kg treatment produced a noticeable
      prolongation of the life span of trypanosome-positive animals. These in vivo
      results suggests that the spiroarsoranes have difficulty in crossing the blood
      brain barrier (BBB) and clearing the parasites from the CNS or, alternatively,
      that these strains are less sensitive to pentavalent arsenicals than the T. b.
      brucei CMP fast strain, which in the present study was more sensitive to
      spiroarsoranes whose lipophilicity corresponded to a log-P value ranging from 2.5
      to 3.7.

PMID- 8738291
TI  - U-73122, an aminosteroid phospholipase C inhibitor, may also block Ca2+ influx
      through phospholipase C-independent mechanism in neutrophil activation.
AB  - 1-[6-[[17 beta-3-Methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1 H-pyrrole-2,5
      dione (U-73122) has been proven to be a useful tool in investigation of
      phospholipase C (PLC)-coupled signal transduction during cell activation. In the
      present studies, the inhibition by U-73122 of cytosolic free Ca2+ concentration
      ([Ca2+]i) of neutrophils was investigated. U-73122 suppressed the [Ca2+]i
      elevation of neutrophils suspended in Ca(2+)-containing medium challenged by N
      formyl-Met-Leu-Phe (fMLP), cyclopiazonic acid (CPA) and ionomycin. The
      concentrations of U-73122 required for inhibition of CPA- and ionomycin-induced
      changes with IC50 values 4.06 +/- 0.27 microM and 4.04 +/- 0.44 microM,
      respectively, is almost 10-times that required for inhibition of the fMLP-induced
      response (IC50 value 0.62 +/- 0.04 microM). U-73122 also reduced the
      intracellular Ca2+ mobilization of neutrophils suspended in Ca(2+)-free medium
      stimulated by fMLP and CPA, but not by ionomycin, with IC50 values 0.52 +/- 0.02
      microM and 6.82 +/- 0.74 microM, respectively. 1-[6-[[17 beta-3-Methoxyestra
      1,3,5(10)-trien-17-yl]amino]hexyl]-2,5-pyrr olidinedione (U-73343), a close
      analog of U-73122 that does not inhibit PLC activity, suppressed the [Ca2+]i
      elevation of neutrophils challenged by fMLP in Ca(2+)-containing medium, but not
      in Ca(2+)-free medium, with IC50 value 22.30 +/- 1.61 microM. In Mn(2+)-quench
      studies, U-73122 suppressed the Mn2+ influx in CPA-activated neutrophils (IC50
      value was 7.16 +/- 0.28 microM) as well as in resting neutrophils (IC50 value was
      6.72 +/- 0.30 microM). U-73343 also suppressed the Mn2+ influx in resting
      neutrophils in a concentration-dependent manner. These results suggest that the
      inhibitory effect of U-73122 on [Ca2+]i of activated neutrophils is attributed
      partly to the suppression of Ca2+ release from the intracellular Ca2+ stores
      through PLC inhibition, and partly to the blockade, especially at higher
      concentrations, of Ca2+ entry from the extracellular space through PLC
      independent processes.

PMID- 8738292
TI  - Acidification of the cytosol inhibits the uptake of tetanus toxin in NG108-15 and
      NBr-10A neurohybridoma cells.
AB  - The influence of cytosol acidification on the uptake of two-chain tetanus toxin
      (TeTX)1 by neurohybridoma cells NG 108-15 and NBr-10A was investigated with two
      established techniques, the NH4Cl pulse method and the pH-clamp method. With the
      former, the extracellular pH is maintained at its physiological value, but is set
      to different values with the latter. Acidification of the cytoplasm with an NH4Cl
      pulse retarded the uptake of TeTX by both NG 108-15 and NBr-10A cells. This
      result provides further evidence for a vesicular endocytotic uptake of TeTX. In
      contrast, acidification of both the external medium and the cytoplasm (pH-clamp
      method) resulted in a net increase of toxin uptake. This result is explained as
      follows: Acidification of the extracellular environment has been shown to
      facilitate the uptake of tetanus toxin, and under pH clamp conditions, this
      effect is stronger than the simultaneous retardation of the toxin uptake by
      acidification also of the cytosol.

PMID- 8738293
TI  - Effect of low concentrations of K+ and Cl- on the Na(+)-dependent neuronal uptake
      of [3H] dopamine.
AB  - The specific uptake of [3H] dopamine (DA) was studied using a crude synaptosomal
      fraction obtained from rat striatum. In a medium containing a 10 mM
      NaHCO3/NaH2PO4 buffer and no added K+ ions, addition of NaCl elicited an increase
      in DA uptake for Na+ concentrations from 10 to 60 mM, and then a decrease of
      uptake for Na+ concentrations up to 130 mM. These data confirm that rather low
      NaCl concentrations produce a maximal DA uptake. This biphasic curve of uptake
      resulted from significant changes in the Vmax of the DA uptake. Except for 10 mM
      Na+, this curve was not significantly modified when 9 mM NaHCO3/NaH2PO4 were
      replaced by 9 mM NaCl. This result indicates that the Cl- dependence of the DA
      uptake is mainly secondary to the Na+ dependence. Addition of KCl up to 3 mM did
      not modify the ascending part of the NaCl-dependent uptake curve. In contrast,
      the reduction in uptake produced by high Na+ concentrations was prevented in a
      concentration-dependent manner by KCl; this effect resulted from a decrease in
      the Km and an increase in the Vmax for the uptake. Measurements of membrane
      potential, with the help of the fluorescent probe 3, 3'-diethylthiadicarbocyanine
      iodide [DiSC2(5)] and purified synaptosomes prepared from rat striatum and
      cerebral cortex, revealed that addition of 3 mM KCl to a medium containing a high
      Na+ concentration and no K+ ions produced a marked and stable decrease in the
      fluorescence level. This decrease which corresponds to an increase in membrane
      polarization was blocked by 0.1 mM ouabain. These data suggest that low K+
      concentrations are likely to prevent the decrease in uptake elicited by high Na+
      concentrations by restoration, via a Na+/K+ ATPase-mediated mechanism, of the
      membrane potential and/or a transmembrane electrochemical Na+ gradient more
      favourable to DA uptake.

PMID- 8738294
TI  - Chronic dexamethasone administration decreases noradrenaline-stimulated, but not
      serotonin-stimulated, phosphoinositide metabolism in the rat brain.
AB  - The present study was undertaken to investigate the effects of chronic
      administration of dexamethasone on the noradrenaline- and serotonin-stimulated (5
      HT-stimulated) phosphoinositide metabolism in hippocampus and frontal cortex of
      the rat brain. For determination of phosphoinositide metabolism, slices from
      selected regions of the rat brain (hippocampus or frontal cortex) were loaded
      with myo- [3H] inositol and stimulated with the agonists (noradrenaline or 5-HT)
      in the presence of LiCl (7.5 mM). Administration of dexamethasone (1 mg/kg/day)
      every 2nd day for 14 days markedly reduced the noradrenaline-stimulated
      phosphoinositide metabolism in the rat hippocampus (IP1: 60% of the control
      value). In the rat frontal cortex, the noradrenaline-stimulated phosphoinositide
      metabolism was less depressed by the chronic administration of dexamethasone
      (IP1: 84% of the control value). However, the chronic administration of
      dexamethasone did not affect the 5-HT-stimulated phosphoinositide metabolism in
      the rat brain. The binding characteristics of alpha 1 -adrenoceptors and 5-HT2A
      receptors were unaffected by the chronic treatment with dexamethasone. These
      results indicate that chronic administration of dexamethasone induces regional
      and neurotransmitter-specific changes of phosphoinositide metabolism in rat
      brain. The results suggest that the reduction of noradrenaline-stimulated
      phosphoinositide metabolism is due to modification of the intracellular signal
      transduction system.

PMID- 8738295
TI  - Functional regulation by dopamine receptors of serotonin release from the rat
      hippocampus: in vivo microdialysis study.
AB  - The functional regulation by dopamine (DA) receptors of serotonin (5-HT) release
      from the rat hippocampus was investigated by use of in vivo microdialysis.
      Dialysate 5-HT levels were reduced by co-perfusion of 10 microM tetrodotoxin
      (TTX) and were elicited by K+ (60 and 120 mM) stimulation in a concentration
      dependent manner. Local perfusion (10 microM) and peripheral administration (20
      mg/kg, i.p.) of fluoxetine produced increases in 5-HT levels. These results
      indicate that the spontaneous 5-HT levels in the rat hippocampus can be used as
      indices of neuronal origin from the serotonergic nerve terminals. The
      nonselective dopamine (DA) receptor agonist apomorphine (1, 10 and 100 microM),
      when perfused through the probe over a period of 40 min, increased 5-HT release
      in a concentration-dependent manner. Apomorphine-induced (100 microM) increases
      in 5-HT release was abolished by pretreatment with the selective D2 receptor
      antagonist, S(-)-sulpiride (1 and 10 microM), but not prevented by pretreatment
      with the selective D1 receptor antagonist, R(+)-SCH-23390 (R(+)-7-chloro-8
      hydroxy-3-methyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine) (1 microM). S(
      )-Sulpiride and R(+)-SCH-23390 by themselves did not alter the spontaneous 5-HT
      levels. The 5-HT release was elevated by perfusion of the selective DA reuptake
      inhibitor GBR 12909 (1-[2-[bis(4-fluorophenyl) methoxy]ethyl]-4-[3-phenyl
      propyl]piperazine) (1, 10 and 100 microM), indicating the possibility of not only
      exogenous but also endogenous DA-mediated facilitatory effects on 5-HT release in
      vivo. The 5-HT release was also elevated by perfused (+/-)-PPHT ((+/-)-2-(N
      phenylethyl-N-propyl)-amino-5-hydroxytetralin) (1, 10 and 100 microM), the
      selective D2 receptor agonist, in a concentration-dependent manner. On the other
      hand, (+/-)-PPHT (100 microM) failed to increase 5-HT release in catecholamine
      (CA)-lesioned rats pretreated with 6-hydroxydopamine (6-OHDA)(200 micrograms/rat,
      i.c.v.). The (+/-)-PPHT-induced (100 microM) increase in 5-HT release was
      prevented not only by pretreatment with 10 microM S(-)-sulpiride but also by
      pretreatment with the alpha 2-adrenoceptor antagonist idazoxan (10 microM). These
      findings suggest that the functional regulation of 5-HT release via D2 receptors
      exists in the rat hippocampus. Furthermore our results indicate that the
      facilitatory effect of 5-HT release via D2 receptors may be mediated indirectly
      by noradrenergic neurons, but not mediated directly through D2 receptors located
      on serotonergic nerve terminals.

PMID- 8738296
TI  - The 5-HT1A receptor antagonist (S)-UH-301 augments the increase in extracellular
      concentrations of 5-HT in the frontal cortex produced by both acute and chronic
      treatment with citalopram.
AB  - In a recent study, utilizing single cell recording techniques, we have shown that
      administration of 5-HT1A receptor antagonists, e.g. (S)-UH-301, to rats
      concomitantly treated, acute or chronically, with the selective serotonin
      reuptake inhibitor (SSRI) citalopram significantly increases the activity of 5
      hydroxytryptamine (5-HT) containing neurons in the dorsal raphe nucleus (DRN).
      Here we report correlative experiments using microdialysis in freely moving
      animals to measure extracellular levels of 5-HT and its metabolite 5
      hydroxyindole acetic acid (5-HIAA) in the frontal cortex, a major projection area
      for DRN-5-HT neurons. Acute administration of (S)-UH-301 (2.5 mg/kg s.c.) or
      citalopram (2.0 mg/kg s.c.) increased 5-HT concentrations with a maximum of about
      70% and 185%, respectively, above baseline. However, when (S)-UH-301 was
      administered 30 min before citalopram the maximal increase in 5-HT levels was
      approximately 400%. In rats chronically treated with citalopram (20 mg/kg/day
      i.p. for 14 days) basal 5-HT concentrations in the frontal cortex were
      significantly increased and 5-HIAA concentrations were decreased when measured 10
      12 h, but not 18-20 h, after the last injection of citalopram, as compared to
      basal 5-HT and 5-HIAA concentrations in chronic saline-treated rats. When (S)-UH
      301 (2.5 mg/kg s.c.) was administered 12 h, but not 20 h, after the last dose of
      citalopram it produced a significantly larger increase in extracellular
      concentrations of 5-HT than in control rats. However, in rats pretreated with a
      single, very high dose of citalopram, 20 mg/kg i.p., administration of (S)-UH-301
      at 12 h after citalopram did not increase 5-HT levels. The augmentation by (S)-UH
      301 of the increase in brain 5-HT output produced by acute administration of
      citalopram is probably due to antagonism of the citalopram induced feedback
      inhibition of 5-HT cells in the DRN, as previously suggested. However, the
      capacity of (S)-UH-301 to further increase the already elevated extracellular
      concentrations of 5-HT in brain in animals maintained on a chronic citalopram
      regimen, in which significant tolerance to the initial feedback inhibition of DRN
      5-HT cells and developed, represents a novel finding. Generally, the reduced
      feedback inhibition of 5-HT neurons obtained with chronic citalopram treatment,
      and the associated elevation of brain 5-HT concentrations, may be related to
      functional desensitization of somatodendritic 5-HT1A autoreceptors in the DRN.
      This phenomenon may also largely explain the larger increase in 5-HT output
      produced by (S)-UH-301 in chronic citalopram treated animals as compared to its
      effect in control animals. Yet, a contributory factor may be a slight, remaining
      feedback inhibition of the 5-HT cells caused by residual citalopram at 12, but
      not 20 h after its last administration. Previous clinical studies suggest that
      addition of a 5-HT1A receptor antagonist to an SSRI in the treatment of
      depression may accelerate the onset of clinical effects. Moreover, in therapy
      resistant cases maintained on SSRI treatment, addition of a 5-HT1A receptor
      antagonist may improve clinical efficacy. Since the therapeutic effect of SSRIs
      in depression has been found to be critically linked to the availability of 5-HT
      in brain, our experiments results support, in principle, both of the above
      clinically based notions.

PMID- 8738297
TI  - In vitro and in vivo effects of the anorectic agent dexfenfluramine on the
      central serotoninergic neuronal systems of non-human primates. A comparison with
      the rat.
AB  - The effects of repeated subcutaneous (s.c) injections of dexfenfluramine (d-F; 10
      mg/kg, twice daily, for 4 days) on the contents of serotonin (5-HT) and its
      metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the brain were assessed in
      primates (cynomolgus and rhesus monkeys) and compared with the regional brain
      concentrations of unchanged drug and its active metabolite, dexnorfenfluramine (d
      NF). This four-day, high-dose, regimen caused a large depletion of 5-HT (more
      than 95%) and of 5-HIAA (80-90%) in all brain areas studied (cortex, hippocampus,
      putamen, caudate nucleus and hypothalamus) 2 h after the last injection of d-F.
      Analysis of the plasma and brain contents of d-F and d-NF confirmed that both
      compounds were concentrated as in other species, in regions of the primate brain.
      However, d-NF was concentrated to a greater extent than d-F, and there were
      differences between the two primate species. Unlike in the rat brain,
      concentrations of d-NF greatly exceeded those of d-F in the primate brain
      suggesting that in these primates the d-NF may play a major role in the overall
      neurochemical response. The effects of d-F and d-NF on different in vitro
      parameters of serotoninergic neuronal function did not show appreciable
      differences between cynomolgus or rhesus monkeys when compared to rats, the
      ability of the two compounds to inhibit 5-HT reuptake, to enhance its release,
      and to affect the binding of [3H] -d-F or of [3H] -mesulergine (a ligand for 5
      HT2C receptors) being similar. Kinetic differences in the disposition of d-F
      appear to have more relevance than biochemical effects in providing an
      explanation for the more marked brain depletion induced by d-F in primates than
      in rodents.

PMID- 8738298
TI  - Somatostatin receptors in the rhesus monkey brain: localization and
      pharmacological characterization.
AB  - To characterize the nature and distribution of somatostatin (SRIF) receptors,
      radioligand binding studies and in vitro receptor autoradiography were performed
      in Rhesus monkey brain using either [125I]LTT-SRIF-28 ([Leu8, D-Trp22, 125I
      Tyr25]SRIF-28) alone or in the presence of 3 nM seglitide (to block sst2 sites),
      [125I]Tyr3-octreotide or [125I]CGP 23996 (c[Asu-Lys-Asn-Phe-Trp-Lys-Thr-Tyr-Thr
      Ser]) in buffer containing either 120 mM Na+ or 5 mM Mg2+. [125I]Tyr3 -octreotide
      labelled an apparently homogeneous population of sites in cerebral and cerebellar
      cortex (Bmax = 27.3 +/- 2.8 fmol/mg protein and 52.6 +/- 8.6 fmol/mg protein, PKd
      = 9.46 +/- 0.03 and] 9.93 +/- 0.03, respectively). The pharmacological profile of
      these sites correlated highly significantly with that of human recombinant sst2
      receptors (r = 0.996), but not or much less with that of human recombinant sst3
      and sst5 receptors (r = 0.12 and 0.45, respectively). [125I]CGP 23996 (in Na(+)
      buffer) also labelled an apparently homogeneous population of sites in Rhesus
      monkey cerebral cortex membranes (Bmax = 3.1 +/- 0.3 fmol/mg protein, pKd = 10.57
      +/- 0.08), the pharmacological profile of which was highly significantly
      correlated with the profiles of human recombinant sst1 and sst4 receptors (r =
      0.98 and 0.96, respectively). Using receptor autoradiography, high levels of
      [125I]LTT-SRIF-28 and [125I]Tyr3 -octreotide recognition sites were found in
      basal ganglia, molecular and granular layers of the cerebellum and layers III, V
      and VI of entorhinal cortex. In these regions, the addition of 3 nM seglitide
      produced a marked decrease of [125I]LTT-SRIF-28 binding. Low levels of [125I]LTT
      SRIF-28 binding were observed in subiculum, pituitary and choroid plexus. By
      contrast, [125I]CGP 23996 labelling in the presence of Mg2+ as well as Na+ ions
      was highest in pituitary and choroid plexus. However, [125I]CGP 23996 binding was
      diversely affected by these ionic conditions in several regions of hippocampus
      and cerebral cortex. Displacement of [125I]CGP 23996 (in Mg(2+)-buffer) with
      seglitide in the molecular layer of the cerebellum, deep layers of the entorhinal
      cortex, layers I, II and V of the insular cortex and frontal pole yielded complex
      competition curves suggesting the presence of two populations of SRIF receptors.
      By contrast, [125I]CGP 23996 binding (in Mg(2+)-buffer) in the choroid plexus,
      hilus of the dentate gyrus and stratum oriens and radiatum of the CA3 field of
      hippocampus was not affected by seglitide up to 10 microM, suggesting only sst1
      and/or sst4 sites which have a negligible affinity for seglitide to be present in
      these structures. Taken together, these results suggest that [125I]CGP 23996 (in
      the presence of Na+) labels exclusively SRIF-2 receptors (sst1 and/or sst4),
      whereas in the presence of Mg2+ ions, [125I]CGP 23996 labels both SRIF-2 and SRIF
      1 receptors (sst2, sst3 and sst5). The present study also demonstrates the
      presence and differential distribution of sst2 and sst1/sst4 receptors in the
      Rhesus monkey brain.

PMID- 8738299
TI  - Chronic beta 1-adrenoceptor blockade sensitises the H1 and H2 receptor systems in
      human atrium: role of cyclic nucleotides.
AB  - We have reported that chronic treatment of patients with beta 1-adrenoceptor
      blockers sensitises isolated atrial preparations to adrenaline, noradrenaline and
      5-Ht. We have now examined the effect of chronic treatment with beta-adrenoceptor
      blockers on responses to histamine of human right atrial appendages. We compared
      the effects of histamine on contractile force, cyclic AMP and cyclic GMP levels
      as well as cyclic AMP-dependent protein kinase (PKA) activity and explored the
      arrhythmogenic effects of histamine in preparations obtained from patients
      chronically treated or not treated with beta-adrenoceptor blockers. Histamine
      increased contractile force in paced preparations; the effects were blocked by
      the H2 receptor antagonist famotidine (0.1-30 mumol/l). The maximum inotropic
      response to histamine was doubled and the inotropic potency of histamine 0.4 log
      units greater in atria from beta-adrenoceptor blocker-treated compared to non
      beta-adrenoceptor blocker-treated patients. Histamine elicited frequency
      dependent arrhythmias that were blocked by famotidine (30 mumol/l) but not by
      mepyramine (1 mumol/l). The incidence of arrhythmias was higher in atria from
      beta-adrenoceptor blocker-treated compared to untreated patients. Histamine
      increased both cyclic AMP and cyclic GMP levels, as well as PKA activity,
      significantly more in atria from beta-adrenoceptor blocker-treated compared to
      those from untreated patients. Mepyramine 1 mumol/l prevented the histamine
      evoked increase in cyclic GMP levels, reduced the inotropic hyperresponsiveness
      and abolished the hyperresponsiveness in cyclic AMP levels and PKA activity
      observed in patients chronically treated with beta blockers. Sodium nitroprusside
      10 mumol/l caused smaller increase of cyclic GMP levels than histamine and
      restored the contracile force depressed by mepyramine to its original level in
      atria from beta-adrenoceptor blocker-treated patients. The evidence is consistent
      with sensitisation of both the histamine H1 and histamine H2 receptor systems by
      chronic beta 1-adrenoceptor blockade. H1 receptor-mediated increases in cyclic
      GMP, enhanced through an as yet unknown mechanism by chronic beta 1-adrenoceptor
      blockade, may inhibit phosphodiesterase 3 activity, thereby causing enhanced
      histamine-evoked increases in cyclic AMP levels and PKA activity, and accounting
      partially for the increased inotropic responses to histamine through H2
      receptors.

PMID- 8738300
TI  - In vivo evidence for the involvement of tachykinin NK3 receptors in the
      hexamethonium-resistant inhibitory transmission in the rat colon.
AB  - In urethane-anaesthetized rats, moderate colonic distention (0.5 ml) induced
      reflex rhythmic contractions (5 mm Hg amplitude and 1.1 cycles/min frequency).
      Senktide (1-10 nmol/kg, i.v.), a tachykinin NK3 receptor selective agonist,
      transiently suppressed distension-induced contractions. SR 142,801 (1-10 mumol/kg
      i.v.), a non-peptide tachykinin NK3 receptor antagonist, had no effect on
      distension-induced contractions but prevented the inhibitory effect of senktide.
      Infusion of N-omega-nitro-1-arginine methyl esther hydrochloride (L-NAME, 20
      mumol/ml/h, i.v) increased the amplitude of colonic contractions and decreased
      the inhibitory effect of senktide. Hexamethonium (15 mumol/ml/h, i.v.) or
      atropine (1 mumol/ml/h, i.v.) inhibited the distension-induced contractions. In
      hexamethonium- or atropine-treated rats, senktide (10 nmol/kg) transiently and
      selectively enhanced the amplitude of contractions. Also SR 142,801 (10
      mumol/kg), but not its inactive enantiomer SR 142,806, increased both amplitude
      and frequency of contractions. During continuous infusion of L-NAME and
      hexamethonium or atropine both frequency and amplitude of distension-induced
      colonic contractions were higher than when in hexamethonium or atropine only.
      Senktide (10 nmol/kg) had no effect and SR 142,801 (10 mumol/kg) produced a
      slight enhancement of colonic contractions. Infusion of sodium nitroprusside (3
      mumol/ml/h, i.v.) decreased amplitude and frequency of distension-induced
      contractions. SR 142,801 had no effect in the presence of the nitric oxide (NO)
      donor. We conclude that tachykinins acting through NK3 receptors exert at least
      four different actions on colonic motility activated by distension: 1) a
      hexamethonium-resistant, NO-dependent, suppressant effect on contractions; 2) a
      hexamethonium-sensitive, NO-independent inhibitory effect on the amplitude of
      contractions; 3) a hexamethonium-resistant, NO-independent inhibitory effect on
      the amplitude of contractions and 4) a hexamethonium resistant and L-NAME
      sensitive excitatory effect on amplitude of contractions. The prevalent
      inhibitory effect evoked in normal conditions along with the excitatory activity
      induced by SR 142,801 on hexamethonium-resistant colonic motility indicates that
      tachykinins, acting through neuronal NK3 receptors, activate NO-dependent and NO
      independent inhibitory neurotransmission in the rat colon.

PMID- 8738301
TI  - Relationship between nitric oxide and platelet-activating factor in castor-oil
      induced mucosal injury in the rat duodenum.
AB  - The modulation of platelet activating factor (PAF) formation in duodenal tissue
      by nitric oxide (NO) released in response to castor oil was studied in rats
      pretreated with NG-nitro-L-arginine methyl ester (L-NAME, 6.25-25 mg/kg, i.p.),
      an inhibitor of NO synthase, NG-nitro-D-arginine methyl ester (D-NAME, 25 mg/kg,
      i.p.), the inactive enantiomer of L-NAME or isosorbide-5-mononitrate (IMN, 30-90
      mg/kg, p.o.), a NO donating compound. Castor oil (2 ml/rat orally) increased PAF
      production in the rat duodenum 3 h after challenge. L-NAME, but not D-NAME,
      enhanced the amount of PAF formed by duodenal tissue, while IMN (30-90 mg/kg)
      counteracted the effects of L-NAME (12.5 mg/kg) and also reduced PAF release in
      the tissue of rats treated with castor oil. L-NAME 12.5 mg/kg, but not D-NAME,
      enhanced both macroscopic damage and acid phosphatase release induced by castor
      oil. These effects were reduced by a PAF antagonist BN 52021 (3-t-Butyl-hexahydro
      4, 7b, 11-trihydroxy-8-methyl-9H-1, 7a-epoxymethano-1H, 6aH-cyclopenta [c] furo
      [2, 3b] furo [3'2':3,4] cyclopenta [1.2-d]furan-5,9,12(4H)trione) 10 and 20 mg/kg
      i.p. Such findings suggest that endogenous nitric oxide could reduce PAF
      biosynthesis in castor oil-treated rats.

PMID- 8738302
TI  - Chloride current in toad skeletal muscle and its modification by the histidine
      modifying reagent diethylpyrocarbonate.
AB  - Cl- currents were measured in short fibres in the toad lumbricalis muscle with a
      two-microelectrode voltage clamp. Membrane Cl- conductance increased markedly
      when external pH was raised. At pH 7 or higher, the Cl- current fell during a
      hyperpolarizing voltage pulse and the rate of inactivation was directly
      proportional to the voltage change. The histidinemodifying reagent
      diethylpyrocarbonate (DEPC, 1 mM) which carbethoxylates histidil residues in
      proteins, suppressed the inactivation of Cl- currents at pH 7.5. On the other
      hand, no apparent changes in the kinetics of the currents at pH 5 were seen. No3-
      currents, which are independent of the extracellular pH and time, were not
      affected by DEPC. Our results support the notion that the inactivation of Cl-
      currents at pH 7.5 represents a membrane permeability change and that DEPC
      interferes with this process. Protonation of histidine groups associated with Cl-
      channels may be the controlling reaction for the pH -dependent Cl- response.

PMID- 8738303
TI  - Aspirin promotes hepatic triacylglycerol accumulation in essential fatty acid
      deficient Japanese quail.
AB  - This study was conducted to investigate whether the effect of a high dose of
      aspirin on hepatic triacylglycerol content is altered by dietary essential fatty
      acids (EFA) in Japanese quail. The birds were given an EFA-free or EFA-adequate
      [containing 2% (w/w) linoleic acid] diet ad libitum from 7 to 24 days of age. On
      the final experimental day, the birds received vehicle or 800 mg aspirin/kg body
      weight intraperitoneally and were killed 4 h subsequently. In birds fed the EFA
      free diet, hepatic triacylglycerol content was more than 2 times higher after
      aspirin compared with vehicle treatment; in contrast, aspirin had no affect in
      birds fed the EFA-adequate diet. Liver malic enzyme and phosphatidate
      phosphohydrolase activities, which are related to lipid synthesis, were not
      affected by dietary EFA or aspirin treatment. Liver carnitine
      palmitoyltransferase activity in the birds fed the EFA-free diet was
      significantly lower than that in the birds fed the EFA-adequate diet, but aspirin
      did not affect this activity. In groups given the EFA-free diet, peroxisomal beta
      oxidation was increased by the aspirin treatment. We conclude that acute
      administration of aspirin to Japanese quail on an EFA-free diet induces hepatic
      triacylglycerol accumulation, and that changes in lipid synthesis and degradation
      do not contribute to this phenomenon.

PMID- 8738304
TI  - Electrophysiological studies of the cholecystokininA receptor antagonists
      SR27897B and PD140548 in the rat isolated nodose ganglion.
AB  - With increased interest in the pharmacology of cholecystokininA (CCKA) receptors,
      including their trophic and mitogenic effects, the actions of two new non-peptide
      CCKA receptor antagonists, PD140548 and SR 27897B, were investigated in a
      convenient model system, the rat isolated nodose ganglion. CCK (1 nM-1 microM)
      caused concentration-dependent depolarisations when superfused over the nodose
      ganglion at 37 degrees C as measured by a silicone grease gap technique, and both
      CCKA antagonists caused significant rightward shifts in the concentration
      response curve to CCK. SR 27897B (3 and 10 nM) caused 7.9- and 17.9-fold shifts
      in the CCK concentration-response curve and the apparent-log KB values for each
      concentration of antagonist were calculated to be 9.36 and 9.23. Further
      experiments with PD140548 (30 and 100 nM) yielded shifts of 2.9- and 12.5-fold
      from which -log KB values were determined to be 7.80 and 8.06. Overall SR 27897B
      was significantly more efficacious than PD140548. Thus, the isolated nodose
      ganglion preparation allows a functional assessment of CCKA-mediated responses,
      with the results indicating that both SR 27897B and PD140548 are efficacious CCKA
      receptor antagonists.

PMID- 8738305
TI  - The mammalian sympathetic prevertebral ganglia: integrative properties and role
      in the nervous control of digestive tract motility.
AB  - The prevertebral ganglia which are a constitutive part of the sympathetic system
      have long been considered as a simple relay on this efferent pathway. In fact,
      these ganglia must be considered as true peripheral nervous centres. They possess
      various integrative properties, such as projections of central and peripheral
      inputs onto the ganglionic neurones, gating of these projections and pacemaker
      activity of the ganglionic neurones. These properties explain the ability of
      these ganglia to participate in the regulation of various visceral functions,
      including digestive tract motility.

PMID- 8738307
TI  - Opioid peptide participates in post-tetanic twitch inhibition in guinea pig
      isolated ileum.
AB  - The effects of a mixture of peptidase inhibitors, consisting of 100 nM each of
      amastatin, phosphoramidon, and captopril, on the twitch inhibitory response (0.1
      Hz, 0.5 ms duration, maximum intensity) exerted by opioid peptides were
      investigated. The opioid peptides, Met-enkephalin (50-200 nM), dynorphin(1-13)
      (0.2-1 nM), and beta h-endorphin (20-100 nM) concentration-dependently inhibited
      the electrically evoked twitch response. In the presence of the mixture of
      peptidase inhibitors, the twitch inhibition evoked by Met-enkephalin was
      significantly increased; however, the twitch inhibition evoked by beta h
      endorphin and dynorphin(1-13) was only slightly increased. These increases were
      abolished by naloxone (NLX; 100 nM). Inhibition of the twitch response (0.1 Hz,
      0.5 ms duration, maximum intensity) induced after high frequency stimulation (10
      Hz, 0.5 ms pulse width, maximum voltage for various lengths of time) (post
      tetanic twitch inhibition) was investigated in isolated guinea pig ileal
      longitudinal muscles. The mixture of peptidase inhibitors, which did not affect
      the twitch response or ACh-contraction, increased post-tetanic twitch inhibition.
      This increase was abolished by naloxone (100 nM). These results suggested that
      the potentiated post-tetanic twitch inhibition evoked by the peptidase inhibitors
      in the ileum was due primarily to mu-ligand(s) rather than to the kappa-type of
      endogenous opioid ligand(s) released from opioidergic neurons.

PMID- 8738306
TI  - Cerebral adenosine triphosphate-sensitive K+ channels may be impaired during
      acute cerebral ischemia in spontaneously hypertensive rats.
AB  - To elucidate the role of cerebral adenosine triphosphate (ATP)-sensitive K+
      channels (KATP) on arterial pressure regulation during acute cerebral ischemia in
      spontaneously hypertensive rats (SHR), intracerebroventricular (i.c.v.)
      injections of either glibenclamide, a specific blocker of KATP, or pinacidil, a
      KATP opener, were performed in SHR and Wistar-Kyoto rats (WKY).
      Intracerebroventricular injections of glibenclamide elicited a vasopressor
      response in WKY with bilateral ligation of the carotid arteries, whereas the
      response was smaller in SHR. It increased plasma AVP, but decreased pituitary AVP
      in WKY with ligation, but not in SHR. Systemic administration of an AVP V1
      receptor antagonist, OPC-21268, abolished the vasopressor responses to i.c.v.
      injections of glibenclamide in WKY. Bilateral ligation of the carotid arteries
      augmented the vasodepressor responses to i.c.v. injections of pinacidil in WKY,
      but not in SHR. Cerebral KATP may play a role in buffering a rise in arterial
      pressure by inhibiting the release of AVP from the pituitary glands during acute
      cerebral ischemia in WKY, but this mechanism might be deranged in SHR, probably
      due to impaired responsiveness of cerebral KATP to ischemia.

PMID- 8738308
TI  - Transplanted sweat glands from mature and aged donors determine cholinergic
      phenotype and altered density of host sympathetic nerves.
AB  - Contact with sweat gland acini causes sympathetic neurons to switch from a
      catecholaminergic to a cholinergic phenotype during development and following
      experimental manipulations. Substantial reductions of cholinergic innervation
      have been shown in the sweat glands of ageing rats and humans. Using in oculo
      transplantation, we have now studied whether sweat gland target tissues retain
      the capacity to regulate changes in the phenotype of sympathetic neurons observed
      in maturity and old age, including a switch from catecholaminergic to cholinergic
      characters. Markers have been used which indicate changes in nerve fibre
      morphology (the pan-neuronal marker, PGP9.5) as well as neurotransmitter
      expression (acetylcholinesterase (AChE), vasocative intestinal polypeptide (VIP)
      and tyrosine hydroxylase (TH)). Sweat glands from young and old donor rats became
      reinnervated by an organotypic pattern of cholinergic host nerves. Surgical
      sympathectomy demonstrated that these cholinergic nerve fibres originate from
      sympathetic neurons of the host superior cervical ganglion (SCG). Retrograde
      tracing combined with staining for VIP (a marker associated with cholinergic
      phenotype in neurons supplying sweat glands) showed that SCG neurons projecting
      to irises with sweat gland implants may be induced to express VIP. We hypothesise
      that these neurons have been switched from their normal catecholaminergic
      phenotype to a cholinergic one by contact with the sweat gland implants.
      Transplants from old donors attracted a density of reinnervation by young host
      nerves which was appropriate to the age of the donor, thus old sweat glands
      received a significantly reduced density of innervation compared to young glands.
      Despite the reduced density of innervation, there was no obvious difference in
      the ability of young and old implants to induce the switch to a cholinergic
      phenotype, suggesting that different mechanisms regulate nerve growth and
      neurotransmitter phenotype.

PMID- 8738309
TI  - Enteric neuropeptides in streptozotocin-diabetic rats; effects of insulin and
      aldose reductase inhibition.
AB  - The aim of the present study was to determine whether diabetes-induced changes in
      the distribution of enteric neuropeptides, could be prevented in 12-week
      streptozotocin-diabetic rats, by rigorous control of glycaemia, using daily
      adminstration of insulin, or an aldose reductase inhibitor (ponalrestat). The
      pattern of distribution of nerve fibres and cell bodies, containing
      immunoreactive vasoactive intestinal polypeptide (VIP), galanin (GAL), calcitonin
      gene-related peptide (CGRP) and substance P was examined in the myenteric plexus
      of ileum from control, untreated diabetic, insulin-treated diabetic and aldose
      reductase inhibitor-treated diabetic rats. The increase in VIP- and GAL-like
      immunoreactivity, seen in the myenteric plexus of untreated diabetic rat ileum,
      was not present in the myenteric plexus of ileum from insulin- and aldose
      reductase inhibitor-treated diabetic rats. With CGRP-like immunoreactive fibres,
      there was a clear decrease in the ileum of untreated diabetic rats. This was
      prevented by insulin treatment, but aldose reductase inhibitor treatment had no
      effect. No alterations in substance P-like immunoreactivity were seen in the
      myenteric plexus of ileum from any of the groups investigated. Generally, the
      similarity of effect of ponalrestat and insulin on VIP and galanin expression in
      this study supports a primary effect of insulin via glycaemic control. The
      dissimilarity of the effect of the two treatments on CGRP expression may imply a
      neurotrophic effect of insulin, although there are certainly consequences of
      hyperglycaemia other than exaggerated flux through the polyol pathway.

PMID- 8738310
TI  - The depletion of monoamines blocks the sympathoinhibitory response to cocaine.
AB  - Recent studies have shown that cocaine decreases, rather than increases
      sympathetic nerve discharge (SND). Whether these sympathoinhibitory responses are
      the result of cocaine's actions on monoaminergic transmission (i.e. blockade of
      neuronal uptake or stimulation of transmitter release) or its local anesthetic
      actions is not known. The purpose of the present study was to determine the
      degree to which cocaine's actions on monoaminergic transmission are involved in
      mediating the sympathoinhibitory response to this drug. We examined the mean
      arterial pressure, heart rate and splanchnic sympathetic nerve responses elicited
      by cocaine (1 mg/kg, i.v.) in pentobarbital-anesthetized rats depleted of
      monoamines. Monoamines were depleted by administering reserpine (10 mg/kg, i.p.)
      either 24, or 48 and 24 h before the experiment. The rats were also given alpha
      methyl-p-tyrosine (200 mg/kg, i.p.) 2 h before the experiment. Vehicle-treated
      rats served as controls. Depletion of monoamines markedly reduced resting
      arterial pressure and heart rate and significantly attenuated the pressor
      response and tachycardia elicited by tyramine (1 mg/kg, i.v.). In control rats,
      cocaine elicited marked (-64 +/- 4%) and prolonged (44 +/- 4 min) decreases in
      SND. The magnitude (-34 +/- 11%) and duration (23 +/- 6 min) of these responses
      were significantly attenuated after 1 day of monoamine depletion. After 2 days of
      depletion, the sympathoinhibitory response was abolished and was replaced by a
      small, brief increase in SND (10 +/- 3%). The pressor responses were similar in
      control and depleted rats, while the bradycardic response (-33 +/- 4 bpm) was
      significantly reduced after 1 and 2 days of monoamine depletion to -20 +/- 3 and 
      15 +/- 2 bpm, respectively. We conclude that a functionally intact monoaminergic
      system is essential for the sympathoinhibitory response to cocaine. Whether the
      pressor responses result from a non-monoaminergic or a reserpine and/or alpha
      methyl-p-tyrosine resistant catecholaminergic mechanism is unknown.

PMID- 8738311
TI  - The inhibitory effect of substance P on gastric motor function in the nucleus
      raphe obscurus is mediated via nitric oxide in the dorsal vagal complex.
AB  - We have previously shown that substance P (SP), microinjected into the caudal
      nucleus raphe obscurus (nROb) of the rat decreases intragastric pressure via a
      vagally mediated pathway. Recent studies from this laboratory demonstrated that
      nitric oxide (NO) synthase is present in the dorsal vagal complex (DVC) and NO
      synthase blockade in the DVC of the rat with NG-nitro-L-arginine methyl ester (L
      NAME) evokes increases in intragastric pressure. Since the nROb controls gastric
      vagal outflow through the DVC, we tested the hypothesis that NO in the DVC is a
      mediator of inhibitory effects of SP on gastric motor function in the nROb.
      Substance P (135 pmol) was microinjected into the nROb 3-6 min after bilateral
      microinjections of L-NAME (45 nmol per site) into the DVC of chloralose
      anesthetized rats were started. Changes in the area of the response for
      intragastric pressure on microinjection of SP after L-NAME did not differ from
      the effect of vehicle microinjected after L-NAME and were significantly lower
      when compared with the effect of SP microinjected after vehicle. We conclude that
      SP in the nROb release NO in the DVC to mediate the inhibitory effect on
      intragastric pressure.

PMID- 8738312
TI  - Delayed onset of action of antidepressant drugs? Survey of results of Zurich meta
      analyses.
AB  - The onset of action of antidepressant drugs was investigated on the basis of two
      independent, multicenter, double-blind studies, comparing amitriptyline (N =
      120), oxaprotiline (N = 120), imipramine (N = 506) and moclobemide (N = 580) with
      placebo (N = 189/+191). Highly significant differences between the active drugs
      and placebo were found with respect to the total number of improvers and the
      total number of responders. In addition, significant differences between
      treatment modalities showed up in both the percentage rate and the time
      distribution of premature withdrawals. However, among improvers, the distribution
      of time spans to onset of improvement was found to be independent of treatment
      modality, indicated by virtually identical cumulative percentages of improvers
      over the whole observation period. This picture of treatment-independent
      improvement rates was essentially the same for the HAMD, HAMA and ZUNG
      assessments, except for a significant time lag between observerratings and self
      ratings. Specifically, our analyses revealed no evidence for a delayed onset of
      action of various antidepressants with large biochemical and pharmacological
      differences when compared to placebo. The early onset of improvement was highly
      predictive of later outcome: on average, 70% of patients showing improvement
      within the first 14 days became responders. Differences between active treatments
      and placebo emerged within the first five days and reached a point of maximum
      distinction around day 14. After this time point, differences between treatment
      modalities remained constant until the end of the observation period. Not more
      than 20-25% of patients were, on average, "true" drug responders, thus suggesting
      that the therapeutic qualities of antidepressants do not lie in the suppression
      of symptoms, but rather relate to their ability to elicit and maintain certain
      conditions which enable recovery in a subgroup of patients who would otherwise
      remain nonresponders.

PMID- 8738313
TI  - Low serum levels of tricyclic antidepressants in amitriptyline- and doxepin
      treated inpatients with depressive syndromes are associated with nonresponse.
AB  - Nonresponse to tricyclic antidepressant (TCA) treatment is observed in about one
      third of depressed patients. The cause(s) for nonresponse - apart from disease
      specific effects - might be the failure to build up sufficiently high serum TCA
      levels due to noncompliance, substance abuse, rapid metabolism, or low dose. We
      carried out a retrospective analysis relating antidepressant serum levels to
      patient data obtained in the naturalistic setting of the Psychiatric Hospital of
      the Bonn University during the introductory phase of drug-monitoring. Case
      reports of 110 depressed inpatients who were treated with amitriptyline or
      doxepin were analyzed with respect to the following: medication and comedication,
      daily dose, type and duration of treatment, serum TCA concentrations (analyzed by
      the fluorescence polarization immunoassay), age, sex, body weight, abuse of
      nicotine or alcohol intake, serum transaminases (ALT, alanine aminotransferase,
      and AST, aspartate amino transferase), gamma-glutamyltranspeptidase (gamma-GT)
      and creatinine, compliance, and response. The salient findings were: 1. Serum TCA
      concentrations increased linearly with the daily amitriptyline dose but not with
      that of doxepin. 2. Interindividually, there was an eight to ten-fold difference
      in serum TCA concentrations at steady-state with 150 mg/day of either drug;
      longitudinally, we observed intraindividually a coefficient of variation of 8%
      and 12% for amitriptyline and doxepin respectively. 3. With amitriptyline (150
      mg/day), the correlation between age and serum TCA concentrations was low (r =
      0.33, p < 0.055) and no correlation was found after the administration of doxepin
      (150 mg/day), nor was there any correlation between age and dose-adjusted serum
      TCA concentrations after the administration of either drug. 4. Nonresponders had
      significantly lower serum levels than responders. These results suggest that
      patients should not qualify as nonresponders unless it can be demonstrated (and
      it is clinically applicable) that the steady-state serum TCA levels are stable
      within the upper limit of the recommended therapeutic range and serum level.

PMID- 8738314
TI  - Effect of prophylactic treatment on suicide risk in patients with major affective
      disorders. Data from a randomized prospective trial.
AB  - Recent findings have indicated that lithium treatment markedly reduces suicide
      risk in major affective disorders. To compare the effect of lithium with
      carbamazepine and amitriptyline, suicidal behavior was analyzed during the
      randomized prospective long-term MAP study (N = 378; duration 2.5 years). Of the
      nine suicides and five attempted suicides, none took place during lithium
      treatment. The findings support the view that lithium has a specific antisuicidal
      effect over and above its prophylactic benefit.

PMID- 8738315
TI  - Pharmacokinetic fluvoxamine-clomipramine interaction with favorable therapeutic
      consequences in therapy-resistant depressive patient.
AB  - We describe the case of a depressive patient who was a rapid metabolizer of
      CYP2D6 substrates and a heavy smoker, and who did not respond to several courses
      of treatment with antidepressants, as a result of unusually low drug-plasma
      levels. During hospitalization, he did not improve after treatment with
      clomipramine (150-225 mg/day during three weeks), but showed a response within
      four days after addition of fluvoxamine (100 mg/day). Plasma levels of
      clomipramine and desmethylclomipramine changed from 58 ng/ml and 87 ng/ml to 223
      ng/ml and 49 ng/ml respectively one week after addition of fluvoxamine. Present
      knowledge of the role of cytochrome P-450 isozymes, such as CYP1A2, CYP2C19,
      CYP2D6, and CYP3A4, in the metabolism of psychotropic drugs as well as
      therapeutic drug-plasma level monitoring may thus help to determine individual
      treatment.

PMID- 8738316
TI  - Considerable improvement in a case of obsessive-compulsive disorder in an
      emotionally unstable personality disorder, borderline type under treatment with
      clozapine.
AB  - We report on a 27-year-old woman with previously therapy-resistant obsessive
      compulsive disorder and emotionally unstable personality disorder, borderline
      type, which improved considerably on treatment with clozapine. Previous treatment
      attempts with paroxetine, clomipramine and various classic and atypical
      neuroleptics, as well as extensive psychotherapeutic treatment, had proved
      ineffective.

PMID- 8738317
TI  - The diagnosis and psychopharmacological treatment of trichotillomania: a review.
AB  - Recently published literature has given rise to two questions: first, can
      trichotillomania be considered a variant of obsessive-compulsive disorder? and
      second, are psychopharmacological treatment strategies, in particular serotonin
      reuptake blockers, effective in the treatment of trichotillomania? The
      differences between trichotillomania and obsessive-compulsive disorder were too
      great to answer the former question affirmatively. To answer the latter question,
      an overview is given of clinical studies on the effects of psychopharmacological
      treatment of adolescents and adults with trichotillomania. A total of three
      studies with control groups and seven without were reviewed. The results varied
      widely and were inconsistent. The conclusion is that no psychopharmacological
      treatment strategies can be recommended so far.

PMID- 8738318
TI  - Fluoxetine and aggressive behaviour.

PMID- 8738319
TI  - Pulsed-field-trapping electrophoresis: a computer simulation study.
AB  - Experimental investigations have shown that adding a large, globular and neutral
      protein (such as streptavidin) at one end of the DNA fragments to be separated by
      gel electrophoresis strongly affects the dynamics of these molecules, leading to
      what is known as trapping electrophoresis (TE). In TE, the velocity decreases
      much more rapidly with DNA molecular size than under normal gel electrophoresis
      conditions, suggesting that TE may be used to increase the power of separation of
      polyacrylamide gel electrophoresis. Unfortunately, the bands are broader and
      fewer readable bands can fit on a single gel slab. Our previous theoretical study
      of TE also predicted the existence of long-lasting anomalous regimes where one
      cannot define a velocity or a diffusion constant. These secondary effects of
      trapping are related to the very broad distribution of detrapping times (the time
      needed to exit a trap). In order to increase the usefulness of TE, it has been
      suggested that pulsed fields may help the molecules exit traps more rapidly. In
      this article, we present a detailed numerical study of pulsed field TE. We
      conclude that simple pulsed fields alone may not be enough to increase the
      sequencing power of polyacrylamide TE because the rate of band broadening cannot
      be controlled. We also report the existence of anomalous regimes in the presence
      of pulsed fields, a factor that has been previously neglected in analytical
      models. Other approaches are also proposed.

PMID- 8738320
TI  - Theoretical permutation gel electrophoretic analysis of a curved DNA fragment
      located in circular permutation.
AB  - Using the theoretical model for DNA curvature, we analyzed a set of fragments
      with a curved insert located in circular permutation. The theoretical permutation
      analysis of each of the cyclically located fragments reveals the presence of a
      shifting molecular bend locus. The delineation of the molecular bend locus
      associated with the fragments obtained by a second permutation helps in providing
      an explanation for the differential mobility behavior of the fragments.

PMID- 8738321
TI  - Influence of optical probing with YOYO on the electrophoretic behavior of the DNA
      molecule.
AB  - The influence of the fluorescent dye YOYO (1,1'-(4,4,8,8,-tetramethyl- 4,8
      diazaundecamethylene)bis[4-[[3-methyl-benzo-1,3-oxazol-2 -yl] methylidene]-1,4
      dihydroquinolinium] tetraiodide) on the electrophoretic behavior of the DNA
      molecule was investigated. This is important when using YOYO as a probe in
      capillary electrophoresis or in fluorescence microscopy studies of DNA with the
      purpose of studying the migration mechanism of DNA on the molecular level. We
      have measured the mobility and orientation dynamics (using the linear dichroism
      technique) for both pure DNA and the YOYO-DNA complex in agarose gel in order to
      compare their electrophoretic properties. Mobility decreases, the degree of
      orientation becomes lower, and the orientational dynamics slower, when YOYO binds
      to DNA. However, the dependence on field strength of the mobility, orientation
      and orientational dynamics, are similar for DNA and YOYO-DNA, indicating that the
      mode of migration does not change significantly upon binding YOYO to DNA.
      Furthermore, since our results show that the effect of YOYO on both the degree of
      orientation and orientational dynamics of the DNA can be measured and therefore
      be compensated for, it can be concluded that YOYO is an excellent optical probe
      for the study of the migrational behavior of DNA.

PMID- 8738322
TI  - An analysis of the dynamic range and linearity of an infrared DNA sequencer.
AB  - We are currently developing genotyping software and protocols for use on the Li
      Cor model 4000(L) infrared fluorescence DNA sequencers. During the development of
      the genotyping software it became apparent that the potential dynamic range of
      the instrument was not being realized when the data collection parameters were
      optimized to produce a high-contrast image on the computer screen. In particular,
      we were unable to obtain peaks with signal to noise (S/N) greater than about 30:1
      and the stronger peaks often saturated the detector. Because the numerical
      dynamic range available in 16-bit data collection mode exceeds 65000, our limited
      dynamic range of about 30 in actual data was somewhat puzzling. Hence, we
      undertook a study to explore the dynamic range and linearity of the Li-Cor DNA
      sequencer in order to minimize background fluorescence and noise as well as
      maximize the available S/N. Data is presented on the background and noise using
      different polyacrylamide gel mixes with various signal gain and offset values,
      and the relative contribution of the glass, gel and instrumentation to the
      background fluorescence is discussed. Based on these results, optimum gain and
      offset values were determined that maintain the background fluorescence at
      approximately 1-2% of the maximum dynamic range with a minimum amount of noise.
      Using these optimized values, we determined the detection system is linear over
      three orders of magnitude by titrating known quantities of an infrared
      fluorophore-labeled primer. In addition, we were able to detect approximately
      15.2 amoles of labeled primer. The results provided by this study establish a set
      of guidelines for evaluating how to set the signal gain and offset in order to
      minimize the background and maximize the S/N and dynamic range of the Li-Cor
      sequencer.

PMID- 8738323
TI  - Marker pattern instabilities as a major cause of reproducibility problems in two
      dimensional DNA fingerprinting.
AB  - Two-dimensional (2-D) DNA fingerprinting is a promising technique for multilocus
      analysis of eukaryotic genomes. It has been successfully applied to the detection
      of DNA variation in tumors, to linkage analyses and to genomic comparisons of
      inbred mouse strains. However, there are still problems with inter-gel
      comparisons of 2-D DNA typing patterns as documented by the inter-gel
      reproducibility rates reported in the literature, which range from 84 to 98%. The
      basis for standardization in almost all of these studies has been a set of lambda
      fragments (digested separately with the restriction enzymes HaeIII, RsaI, Bg/I)
      that produces a spot pattern scattered across the gel. These spots are used as
      markers for gel comparisons. Since we noticed considerable variations in the
      marker spot patterns, we evaluated the properties of the lambda marker using both
      computer simulation and an empirical analysis of forty independent consecutive
      gels from our laboratory. We explain the instabilities of the spot pattern on the
      basis of the melting properties of the individual lambda fragments. A subset of
      spots is presented that has been stable in all our experiments. Only this set of
      spots should be used for gel standardization purposes until a new, completely
      reproducible marker becomes available. Finally, suggestions for an improved
      marker system are made.

PMID- 8738324
TI  - Molecular analysis of Salmonella enterica serotype Dublin: building bridges
      between population genetic and molecular epidemiological studies.
AB  - Population genetic studies of Salmonella enterica serotype Dublin using
      multilocus enzyme electrophoresis have recognised two dominant clones termed Du1
      and Du3. The characterisation of plasmids in Dublin suggests greater strain
      diversity. The application of restriction enzyme fragmentation pattern (REFP)
      analysis of genomic DNA using Sau3A and HincII together with plasmid subtractive
      analysis can resolve anomalies in earlier comparisons. Twenty-six isolates were
      selected for inclusion in the study. All had been previously characterised with
      respect to their plasmids, and were isolated from the USA, Canada and five
      European countries. On the basis of plasmid profiles, 17 were predicted to
      correspond with Du1 and Du3. Sau3A digestion generated two distinct REFPs (A and
      B) of < 70% similarity, which corresponded with Du1 and Du3. After the
      contribution of plasmid-derived bands was subtracted, two variants of A (A1 and
      A2) and four of B (B1, B2, B3 and B4) were recognised. Seventeen were concordant
      with predictions from population genetic studies. Nine that could not be
      predicted on the basis of atypical plasmid profiles all showed REFP A1 (Du1) and
      were consistent with the incursion of additional plasmids or plasmid
      cointegration. REFPs from HincII digests generally corroborated Sau3A data but
      showed greater overall similarity between the strains and more influence from
      plasmid DNA.

PMID- 8738325
TI  - Precast commercial polyacrylamide gels for separation of DNA amplificates by
      temperature gradient gel electrophoresis: application to clonality analysis of
      lymphomas.
AB  - The third complementary determining region (CDR-III) of the rearranged
      immunoglobulin heavy chain (IgH) genes represents a unique marker for a
      lymphocyte and its clonal descendants and can be amplified by the polymerase
      chain reaction (PCR) technique. This approach has markedly enhanced the
      sensitivity for detection of clonal lymphocyte populations in patients with
      malignant B-lymphoid neoplasias. To monitor minimal residual disease (MRD) in
      tissue specimens during or after antineoplastic treatment, the problem of
      detecting the presence of a few clonal (malignant) lymphocytes in coexistence
      with a majority of polyclonal lymphocytes has to be addressed. Semi-nested PCR
      amplification of CDR-III rearrangements from specimen infiltrated by tumor cells
      generates clonal signals in front of a polyclonal background, and therefore high
      resolution electrophoretic techniques for separation of DNA fragments are
      required. Temperature gradient gel electrophoresis (TGGE) resolving DNA homo- and
      heteroduplexes according to their thermal stability has been successfully applied
      for this purpose using special electrophoretic equipment. We describe an
      adjustment to this technique by using a commercially available precast 0.5 mm
      thick polyacrylamide gel and by changing a standard horizontal electrophoretic
      device into a TGGE device. By this means we screened patients with B-cell
      lymphoma undergoing high-dosage radiochemotherapy followed by autologous
      transplantation for continuous presence of clonal (tumor-specific) CDR-III
      rearrangements. Specimens from blood and bone marrow were collected on diagnosis
      as well as before and after autologous transplantation. In addition, the
      autograft (bone marrow or peripheral blood hematopoietic stem cells) was
      analyzed. Tumor cells were easily detected in the transplants and in specimens
      collected during follow-up examinations. The clinical value of these findings
      remains unclear as yet because the number of cases investigated was small and the
      follow-up time is still too short. However, we conclude that the technique of
      combining the sensitivity of PCR with the specificity of high resolution TGGE is
      easy to use, making it possible to handle, in a clinical routine, a great number
      of samples within a short time in order to monitor MRD in patients with B-cell
      neoplasias.

PMID- 8738326
TI  - Improved conditions for the analysis of large variable number of tandemly
      repeated (VNTR) unit polymorphisms.
AB  - Large variable number of tandemly repeated (VNTR) unit polymorphisms were
      identified by amplification of genomic DNA with appropriate primers, followed by
      agarose gel electrophoresis and ethidium bromide staining. However, when genomic
      DNA was extracted using paramagnetic beads, we found that the efficiency of
      polymerase chain reaction amplification of VNTR's was affected by the purity of
      the solid phase-eluted DNA. Here we report that VNTR's located in the human
      interleukin-1 receptor antagonist and interleukin-4 genes are clearly and
      reliably amplified only when more stringent conditions are used in order to
      obtain purer DNA eluates from DNA-bead complexes. In addition, polyacrylamide gel
      electrophoresis followed by silver staining is superior to ethidium bromide
      staining of agarose gels in visualizing the different allelic bands of
      heterozygous carriers.

PMID- 8738327
TI  - High resolution slab gel electrophoresis of 8-amino-1,3, 6-pyrenetrisulfonic acid
      (APTS) tagged oligosaccharides using a DNA sequencer.
AB  - A novel electrophoretic method for the analysis of oligosaccharides using DNA
      sequencer technology is illustrated using malto-oligosaccharide distributions
      obtained following isoamylase digestion of glycogen, wheat starch and potato
      starch. The debranched starches were derivatized at the reducing and with the
      charged fluorophore 8-amino-1,3,6-pyrenetrisulfonic acid (APTS). This highly
      reproducible method provides baseline resolution of oligomers from chain lengths
      of 3 to more than 80 glucose units, and exhibits high sensitivity with detection
      thresholds of one femtomole per resolved band. In addition, the reductive
      amination procedure attaches a single fluorophore per oligosaccharide, allowing
      calculation of the results on either a mass or a molar basis. The efficacy of the
      method is illustrated through the determination of the profile of individual
      oligosaccharides of chain length with a degree of polymerization (DP) < 80,
      derived from loading less than 15 ng per analysis of glycogen, wheat and potato
      starches. While the results obtained were superior in resolution and sensitivity
      to previously reported observations using a range of techniques, they were
      nonetheless consistent with the overall differences between these
      polysaccharides. The resolution, sensitivity, reproducibility and high throughput
      of the method provides substantial advantages over existing methods for the
      analysis of linear oligosaccharide chain length distributions.

PMID- 8738328
TI  - Pyrogallol red-molybdate: a reversible, metal chelate stain for detection of
      proteins immobilized on membrane supports.
AB  - Certain metal complexes selectively interact with proteins immobilized on solid
      phase membrane supports to form brightly colored products. The metal chelates
      form protein-dye complexes in the presence of metal ions at acidic pH but are
      eluted from the proteins by immersing membranes in a solution of basic pH that
      contains other chelating agents. The reversible nature of the protein staining
      procedure allows for subsequent biochemical analyses, such as immunoblotting, N
      terminal and internal protein sequencing. Among the metal complexes evaluated to
      date, the triazine dye-ferrous complexes (ferene S, ferrozine) and the
      ferrocyanide-ferric complexes provide the most sensitive detection of proteins
      immobilized on membranes. While the pyrogallol red-molybdate complex is commonly
      used in solution-based total protein assays, its utility as a reversible stain
      for proteins immobilized on membranes has not been reported. Pyrogallol red
      molybdate complexes readily stain proteins on nitrocellulose and polyvinyl
      difluoride membranes with similar sensitivity as ferrozine-ferrous complexes.
      Analysis of charge-fractionated carrier ampholytes and synthetic polymers of
      different L-amino acids indicate that binding is prominently via protonated alpha
      and epsilon-amino side chains. Carbamylation of amino groups in bovine serum
      albumin substantially diminishes pyrogallol red-molybdate binding to the protein.
      The stain is reversible, resistant to chemical interference, and compatible with
      immunoblotting.

PMID- 8738329
TI  - From image processing to classification: IV. Classification of electrophoretic
      patterns by neural networks and statistical methods enable quality assessment of
      wheat varieties for breadmaking.
AB  - The end-use quality of products made from doughs consisting of wheat flour and
      water is often dependent upon the storage (gluten) proteins of the grain
      endosperm. Today the electrophoretic patterns of the high molecular weight (HMW)
      glutenin subunits are used for quality selections in wheat breeding programs in
      several countries. In this study, we used two multivariate techniques to classify
      digitized patterns from isoelectric focusing of gliadins and glutenins: a two
      layered neural network architecture consisting of a self-organizing feature map
      and a feed-forward classifier [1], and discriminant analysis [2,3]. Three groups
      of seven wheat varieties (Triticum aestivum L.), associated with poor, medium or
      good properties in relation to bread-making quality, were used. The best
      classification results were obtained by the neural network model, based on data
      from the gliadin fraction: it was possible to classify varieties associated with
      poor or good quality, with recognition rates of 70 and 69%, respectively. The
      statistical method was better suited to solve the classification problem when the
      data was based on the glutenin fraction: if a specific variety was already known
      to be non-poor, this method enabled us to classify the medium- and good-quality
      classes with recognition rates of 90 and 88%, respectively. The results obtained
      were confirmed by correlation coefficients.

PMID- 8738330
TI  - Enhanced field strength and resolution in gel electrophoresis upon substitution
      of buffer by histidine at its isoelectric point.
AB  - Gel electrophoresis in isoelectric buffers, recently introduced by R. Westermeier
      and H. Schickle (Electrophoresis '95, Paris, Abstract No.3, 1995), was applied to
      the automated HPGE-1000 apparatus in the expectation to be able to increase the
      field strength under the limiting conditions of heat dissipation capacity and
      voltage of that apparatus. A previous attempt to achieve that aim by reduction of
      gel thickness had not yielded more than a twofold increment in resolving power.
      Replacing 0.2 X Tris-boric acid-EDTA (TBE) buffer, conventionally applied in the
      apparatus at 15 V/cm, by 0.05 M histidine, pH 7.6 (close to the pI of 7.47),
      allows one to increase the field strength to 60 V/cm, thus providing a nearly
      fivefold increment in resolution under otherwise identical conditions
      (fluorescein carboxylate-labeled conalbumin-sodium dodecyl sulfate (SDS) and
      soybean trypsin inhibitor-SDS samples, 10 degrees C, 4% MetaPhor agarose). An
      additional decrease in band dispersion can be obtained by decreasing the starting
      zone width through buffer dilution in the sample phase.

PMID- 8738331
TI  - Sample-streaks and smears in immobilized pH gradient gels.
AB  - In immobilized pH gradient (IPG) gel formulations as wide as pH 4-9, encompassing
      neutrality and containing the pK 7.0 acrylamido buffer as one of the buffering
      ions, smears are directly proportional to the total amount of the pK 7.0 species.
      At a total level of 10 mM pK 7.0 in these gel formulations, severe smears occur
      not only for mildly hydrophobic proteins (e.g., recombinant alcalase and
      termamylase) but also for the relatively hydrophilic pI marker proteins. Streaks
      and smears are essentially abolished in recipes devoid of the pK 7.0 compound or
      in formulations containing a maximum of 3 mM of this component. Although
      partitioning in water/n-octanol has shown the pK 7.0 acrylamido buffer to be
      quite hydrophobic (P = 0.5), the occurrence of smears could be to the presence of
      oligomers in some commercial preparations. Even when dissolved in n-propanol,
      some batches of acrylamido buffers might still contain oligomers, probably formed
      during the synthetic step.

PMID- 8738332
TI  - Electrophoretic separation of multiprotein complexes from blood platelets and
      cell lines: technique for the analysis of diseases with defects in oxidative
      phosphorylation.
AB  - A two-dimensional electrophoretic technique combining blue native polyacrylamide
      gel electrophoresis (BN-PAGE) with Tricine sodium dodecyl sulfate (SDS)-PAGE was
      previously used for the localization of oxidative phosphorylation (OXPHOS)
      defects in human diseases starting from biopsy or autopsy tissues (Schagger, H.,
      Electrophoresis 1995, 16, 763-770). In the present work the technique was
      extended for the resolution of OXPHOS enzymes from platelets and tissue-cultured
      cells. Silver staining is required to detect the protein subunits of OXPHOS
      complexes in two-dimensional gels. However, the use of cultured cells has major
      implications for patients with mitochondrial encephalomyopathies since it will
      reduce the number of invasive muscle biopsies. The ease of isolating the platelet
      membrane glycoprotein complex from a few milliliters of blood makes it possible
      to analyze this complex and its protein subunits in bleeding disorders like
      Glanzmann's thrombasthenia.

PMID- 8738333
TI  - Quantitation of the water channel protein aquaporin (CHIP28) from red blood cell
      membranes by densitometry of silver stained polyacrylamide gels.
AB  - A protein determination procedure which involves the densitometry of silver
      stained polyacrylamide gels is described. It involves calibration with bovine
      serum albumin and molecular weight markers on the same gel with the protein to be
      quantitated. The procedure is simple, rapid, reproducible and accurate and is
      more sensitive than other procedures for protein determination. The procedure is
      particularly useful in quantitating proteins purified in small amounts since the
      determination can be performed on the same gel used to check the purification. It
      avoids interference by detergents and other substances usually present in
      solutions of purified proteins. The procedure has been applied to the
      quantitation of a recently identified protein, aquaporin (CHIP28), assumed to be
      a major water channel in the red blood cell membrane. A quantitative analysis of
      a purified fraction of this protein shows that the 28 kDa component represents
      approximately two thirds of the protein content of the sample, with the remainder
      comprising a glycosylated, high molecular mass component. The procedure may be
      useful for quantitating proteins revealed on silver stained gels and could be
      included as a standard part of any protocol for protein purification.

PMID- 8738334
TI  - Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and centrifuge
      blotting: preparation of polypeptides for amino-terminal sequence analysis.
AB  - The applicability and reproducibility of a previously described (L. F. Hermansen
      et al., Electrophoresis 1993, 14, 1302-1306) centrifuge-blotting procedure for
      capturing subnanomolar amounts of protein on polyvinylidene difluoride membranes
      for direct Edman degradation was further investigated. Proteins with different
      molecular masses were centrifuge-blotted onto Immobilon CD membranes.
      Simultaneous blotting and desalting was achieved with an overall yield of 15-56%
      after 2 h centrifugation for proteins with a molecular mass of 12-30 kDa.
      Centrifugation of myoglobin for 6 h resulted in an overall yield of 72%. The
      subnanomolar amounts obtained were also sufficient to conduct cyanogen bromide
      cleavage in situ on proteins with blocked NH2-terminus and to generate sequence
      information.

PMID- 8738335
TI  - Novel acrylamido monomers with higher hydrophilicity and improved hydrolytic
      stability: I. Synthetic route and product characterization.
AB  - The novel acrylamido monomer reported by our group (N-acryloylaminoethoxyethanol,
      AAEE; Chiari et al., Electrophoresis 1994, 15, 177-186), found to combine high
      hydrophilicity with extraordinary resistance to alkaline hydrolysis, has come
      under closer scrutiny due to unexpected and random autopolymerization while
      stored as a 1/1 v/v water solution at 4 degrees C (possibly due to a greater
      oxidability of the ether group). We have additionally found a unique degradation
      pathway of the monomer, called "1-6 H-transfer", by which the C1 (on the double
      bond site), by constantly ramming against the C6, next to the ether oxygen (O7,
      which in fact favors the transfer of the hydrogen atom by C1), produces radicals
      which more efficiently add to the monomer favoring autopolymerization and cross
      linking. A number of novel monomers is proposed while maintaining the other
      unique characteristics of AAEE. One of them, N-acryloylaminopropanol, offers all
      the unique, special qualities of AAEE, without the noxious aspects of
      autopolymerization. Additionally, a synthetic route was optimized, yielding an
      essentially pure product in a single reaction step, with a yield > 99% and an
      equivalent purity (> 99%). The synthesis consists in reacting acryloyl chloride
      at -40 degrees C in presence of a twofold molar excess of aminopropanol and in
      ethanol (instead of methanol) as solvent. Other solvents, as well as the use of
      triethylamine for neutralizing the HCl produced, were found to give a variety of
      undesired byproducts.

PMID- 8738336
TI  - Novel acrylamido monomers with higher hydrophilicity and improved hydrolytic
      stability: II. Properties of N-acryloylaminopropanol.
AB  - The physico-chemical properties and the electrophoretic behavior of the novel set
      of monomers reported by (Simo-Alfonso et al., Electrophoresis 1996, 17, 723-731)
      have been evaluated. Of utmost importance was the combination of high
      hydrophilicity and extreme hydrolytic stability, most desired properties for, any
      electrophoretic matrix, especially for protein fractionation. One of these
      monomers (N-acryloylaminopropanol, AAP) was found indeed to be extremely
      hydrophilic (with a partition coefficient P of only 0.10, vs. P = 0.13 for N
      acryloylaminoethoxyethanol and P = 0.20 for acrylamide) and to possess excellent
      stability to alkaline hydrolysis. Its hydrolysis constant (0.008 L mol-1 min-1),
      as a free monomer, in an alkaline milieu, was found to be about one order of
      magnitude lower than conventional acrylamide (0.05 L mol-1 min-1). In the polymer
      state, the resistance to hydrolysis of poly(AAP) was assessed as 500 times
      greater than a conventional poly(acrylamide) matrix.

PMID- 8738337
TI  - Novel acrylamido monomers with higher hydrophilicity and improved hydrolytic
      stability: III. DNA separations by capillary electrophoresis in poly (N
      acryloylaminopropanol).
AB  - Separation of DNA fragments in a novel polymer network, consisting of N
      acryloylaminopropanol (AAP) is reported. The performance of this novel monomer,
      as a sieving liquid polymer in capillary zone electrophoresis, was evaluated. In
      50 microns ID capillaries, an 8% solution of poly (AAP) can afford apex
      resolution of the 123/124 bp adjacent pair of DNA fragments in marker V,
      typically unresolved in any poly (acrylamide) formulation. It is proposed that
      the distal-OH group in the AAP molecule can form transient H-bonds with the DNA
      double helix. Molecular modeling shows a meandering structure for poly (AAP),
      lacing the walls of half a cylinder, with kinks protruding at regular intervals,
      potentially able to fit into the major groove of DNA. Contrary to previously held
      beliefs, there seems to be a minimum length of the polymer for proper sieving of
      DNAs. For poly (acrylamides), a weight average molecular mass Mw 30 000 polymer
      offers no resolution, whereas a polymer of 250 000 to 400 000 Da exhibits optimum
      resolving power. For poly (AAP), the optimal length is in excess of 450 000 Da in
      Mw. Thus, it is shown that both the chemical composition of the monomer and the
      length of the polymer play a subtle, cooperative role in DNA separation.

PMID- 8738338
TI  - The effects of polymer properties on DNA separations by capillary electrophoresis
      in uncross-linked polymer solutions.
AB  - Low-viscosity, aqueous solutions of hydrophilic linear polymers have been shown
      to be useful for the separation of DNA restriction fragments by capillary
      electrophoresis (CE). However, the choice of polymer type, size, and
      concentration remains largely empirical, because the mechanism of high-field
      electrophoretic DNA separations in polymer solutions is not well understood. To
      assist in elucidating the mechanism of DNA separation, we experimentally
      investigated the effects of polymer properties such as stiffness (persistence
      length), average molecular mass, polydispersity, and hydrophilicity on the
      separation of DNA ranging from 72 bp to 23 kbp. This was accomplished by
      comparing the results of DNA separations obtained by counter-migration CE in
      dilute and semidilute solutions of linear polyacrylamide (PAA), hydroxyethyl
      cellulose (HEC), and hydroxypropylcellulose (HPC) polymers of several different
      average molecular masses.

PMID- 8738340
TI  - Calculation of modified capacity factor in micellar electrokinetic
      chromatography.
AB  - In addition to the expression k' = (tm-t(o))/t(o) (1-tm/tmc), we propose the
      expression k" = (tm-t(o))/(tmc-t(o)) to calculate the capacity factor in micellar
      electrokinetic chromatography (MEKC), where tm, t(o), and tmc are the migration
      time of the analyte, the flow marker, and the micelles, respectively. The k' and
      k" values that were obtained from simulated data as well as from MEKC analysis of
      different peptides (in 100 mM sodium dodecyl sulfate/0.1 N sodium borate buffer
      at pH 11.0) were calculated and compared. The k" value is equal to zero for an
      analyte remaining in the aqueous phase whereas it is equal to one for an analyte
      always staying in the micellar phase. By applying k" a finite capacity factor can
      be obtained for an analyte, indicating its partition between the two moving
      phases (aqueous and micellar) even in those cases when tm equals tmc. The slope
      of the curve k" as a function of tm is constant through the whole migration
      window and therefore peak compression does not occur when applying k" to
      calculate the capacity factor. A given difference in k" corresponds the same
      difference in migration times and this value does not depend on the position
      within the migration window. Since k" is a normalized parameter it is easy to
      evaluate the significance of a given difference in capacity factor or to estimate
      the relative position of an analyte with a given capacity factor in the migration
      window by applying k". Therefore, k" seems to be an adequate parameter to
      calculate the capacity factor in MEKC and, similar to K', it also refers to the
      hydrophobicity of the analyte.

PMID- 8738339
TI  - Comparative analysis of somatostatin analog peptides by capillary electrophoresis
      and micellar elektrokinetic chromatography.
AB  - Capillary electrophoresis (CE) and micellar electrokinetic chromatography (MEKC)
      methods, utilizing uncoated silica capillary and triethyl ammonium phosphate or
      sodium borate buffers in the pH range of 2.25-11.0, containing sodium dodecyl
      sulfate (SDS) (0-100 mM) for analysis of somatostatin-analog peptides were
      developed. The method presented here was compared with the reversed-phase high
      performance liquid chromatographic (RP-HPLC) and CE methods developed for
      analysis of peptides. The peptides investigated in this work can be separated by
      CE on the basis of their electrophoretic mobility in aqueous buffer of low pH
      value (pH 2.25) or by MEKC on the basis of their hydrophobicity in SDS containing
      buffer of high pH value (pH 11.0). Optimal MEKC separation of the investigated
      peptides has been achieved at pH 11.0 in an Na-borate buffer containing 100 mM
      SDS. CE at pH 2.25 proved insensitive to the hydrophobicity of the peptides
      investigated. By contrast, results obtained with MEKC at pH 11.0 proved to be
      anologous to those obtained by RP-HPLC, with highly hydrophobic peptides
      migrating slower than peptides without hydrophobic moieties.

PMID- 8738341
TI  - Capillary-zone electrophoresis in agarose gels using absorption imaging
      detection.
AB  - A simple home-built electrophoretic unit and a commercially available charge
      coupled device (CCD) camera with image acquisition and analysis software were
      used to study the separation process in zone electrophoresis experiments in 4 cm
      long, round capillaries (inside diameter 0.2 mm). Several capillaries could be
      investigated simultaneously. The absorption imaging system was used not only to
      follow the course of the separation but also to study the interaction between
      biologically active substances (proteins, detergents, enzymes and-substrate).
      Since the system allows visual on-line observation of the separation one can
      rapidly decide when the analysis is finished, which often shortens the analysis
      time. The electrophoresis method presented is suitable also for preparative runs,
      since direct visualizations of a solute zone allows it to be excised and then
      used for further studies.

PMID- 8738343
TI  - Separation and isolation of subcellular-sized particles by electrophoresis in
      polymer solution using the commercial scanning apparatus.
AB  - Electrophoresis of fluorescently labeled rat liver microsomes and polystyrene
      carboxylates of 10 and 30 nm radius was conducted in buffered 10-15%
      polyvinylpyrrolidone (M(r) = 10(6) solutions, using a horizontal gel
      electrophoresis apparatus with intermittent scanning of fluorescence (HPGE-1000,
      LabIntelligence). Banding, constant migration rates and Ferguson plots were
      obtained in these polymer solutions. The major microsome band detected by the
      automated scan was located visually on the gel by means of its fluorescein label
      and was isolated by volumetric withdrawal, recovery was monitored by scanning and
      ascertained to be near quantitative after three consecutive steps, in each of
      which 30 microL were withdrawn. This preparative method promises to be generally
      applicable to particles that are too large to enter into gels.

PMID- 8738342
TI  - The role of pH and membrane porosity in preparative electrophoresis.
AB  - The Gradiflow is a preparative electrophoresis apparatus, allowing fractionation
      based on a combination of size and charge of proteins in their native (unreduced)
      form. The preparative fractionation of two proteins of similar size and
      isoelectric point is demonstrated using the Gradiflow. A separation membrane of
      appropriate pore size was chosen and then fractionation was "fine tuned" by
      selecting an appropriate buffer pH to accentuate charge differences between the
      proteins of interest. Complete separation of mg quantities of bovine serum
      albumin and ovalbumin was achieved within 40 min.

PMID- 8738344
TI  - Isolation of proteins and nucleic acids by electrophoresis on disposable gel
      columns.
AB  - A simple and cheap one-step method to isolate proteins or nucleic acids by
      electrophoresis in disposable gel columns is reported. A disposable syringe was
      modified to host a gel column and an elution chamber. Starting from a crude
      extract of E. coli, the laboratory-made devise allowed the isolation of the
      maltose binding protein (MBP) fused to a recombinant allergenic molecule with a
      molecular mass of 58 kDa, from a mixture of several proteins. Also, plasmid DNA
      could be isolated from a mixture containing chromosomal DNA and RNA, avoiding the
      use of organic solvents. Electrophoresis was performed at 150 V, 35 degrees C, pH
      8.0 and 8.3 for protein and DNA, respectively. The protein or the DNA obtained
      showed a yield of 80% and a purity grade of 90%, as estimated by densitometry.

PMID- 8738345
TI  - Thermostable variants of subtilisin selected by temperature-gradient gel
      electrophoresis.
AB  - Region-specific random mutagenesis in the weak calcium binding site of subtilisin
      Carlsberg and subsequent screening for variants with enhanced heat stability
      revealed two variants, which showed significantly enhanced residual activity at
      68 degrees C, 0.1 mM CaCl2, pH 8.0. Preselected variants have been studied by
      temperature-gradient gel electrophoresis (TGGE) and were found to be stabilized
      due to different effects. Whereas the point mutation (Ser188Pro) mainly enhanced
      autoproteolytic stability of subtilisin, the double mutation (Ser188Pro;
      Ala194Glu) additionally increased the apparent Tm-value of the molecule for 2-3
      degrees C under a variety of conditions. It was possible to differentiate between
      the effects of autoproteolysis and structural unfolding to a certain degree by
      TGGE and to show the complex influence of changed calcium affinity on thermal
      stability for the double variant.

PMID- 8738346
TI  - Alpha-2-HS-glycoprotein (AHSG) polymorphism in semen and saliva.
AB  - Polymorphism of alpha-2-HS-glycoprotein (AHSG) was demonstrated in human semen
      and whole saliva samples by thin-layer polyacrylamide gel isoelectric focusing
      (IEF) and immunoblotting. Although the seminal AHSG IEF patterns were found to
      differ from those of plasma AHSG from the corresponding donors, incorporation of
      Nonidet P-40 into the IEF gel (pH 4.2-4.9) enabled us to phenotype seminal AHSG
      correctly. Salivary AHSG, however, exhibited IEF patterns similar to those of the
      corresponding plasma AHSG. By treating the samples with neuraminidase, it was
      possible to determine the AHSG types using 2-5 microL semen and 50-100 microL
      whole saliva samples. The AHSG types determined separately in 47 sets of semen,
      whole saliva, urine and plasma samples from the same donors correlated perfectly
      with each other. AHSG typing could, therefore, provide an additional discriminant
      characteristic in the forensic examination of semen and saliva samples.

PMID- 8738347
TI  - Protein degradation in human pure pancreatic juice analyzed by two-dimensional
      gel electrophoresis.
AB  - Two-dimensional gel electrophoresis (2-DE) was used to study protein degradation
      in human pure pancreatic juice (PPJ) which was collected at 5 min intervals for
      20 min by selective endoscopic cannulation of the main pancreatic duct. In PPJ
      collected from healthy subjects no significant degradation was observed by
      incubating PPJ at 37 degrees C up to 6 h. By further incubation for 24 h,
      glycoprotein-1, procarboxypeptidase A-1 and lipase were nearly completely
      degraded, while alpha-amylase and procarboxypeptidase B-1 were not degraded under
      these conditions; alpha-amylase became labile in the presence of 1 mM ethylene
      diaminetetraacetic acid (EDTA) or 10 mM phenyl methyl sulfonyl fluoride (PMSF).
      Protein degradation was observed by 2-DE of an initial fraction of PPJ collected
      from patients with chronic calcific pancreatitis (CCP). The 2-DE patterns of
      subsequent fractions resembled those of PPJ from healthy subjects. The mixture of
      the last fraction with the initial fraction showed significant protein
      degradation, inhibited by adding aprotinin. Furthermore, the extent of protein
      degradation correlated with the dilatation of the main pancreatic duct as a
      consequence of intraductal stagnation of pancreatic juice. These findings
      demonstrate that protein degradation in PPJ is accelerated by intraductal
      activation of serine proteases in the case of patients with CCP. 2-DE of PPJ from
      patients with CCP provides useful information for the evaluation of intraductal
      activation of zymogens and the progress of chronic pancreatitis.

PMID- 8738348
TI  - Identification of stress proteins in endothelial cells.
AB  - Endothelial cells have been shown to play a major role in the pathophysiology of
      various diseases including ischemic heart disease and viral infection leading to
      myocarditis or dilated cardiomyopathy, conditions in which stress proteins (heat
      shock protein-hsp; glucose-related protein - grp) are likely to be involved. For
      further characterization of stress proteins and their possible role in these
      diseases, the major stress proteins in human endothelial cells were separated by
      two-dimensional polyacrylamide gel electrophoresis with immobilized pH gradients
      in the first dimension and identified by immunoblotting and either N-terminal or
      internal amino acid sequencing, respectively. Ubiquitin, hsp27, hsp60, hsp70,
      heat shock cognate protein 70, grp78 and grp75 were found to be constitutively
      expressed; hsp72 was found in stressed cells, exclusively, in line with results
      obtained in other human cell lines. Three additional proteins with molecular
      masses between 34 and 40 were regularly detected in stressed cells that were
      found to have identical amino acid sequences with those of members of the hsp70
      family.

PMID- 8738349
TI  - Health and immunology study following exposure to toxigenic fungi (Stachybotrys
      chartarum) in a water-damaged office environment.
AB  - There is growing concern about adverse health effects of fungal bio-aerosols on
      occupants of water-damaged buildings. Accidental, occupational exposure in a
      nonagricultural setting has not been investigated using modern immunological
      laboratory tests. The objective of this study was to evaluate the health status
      of office workers after exposure to fungal bio-aerosols, especially Stachybotrys
      chartarum (atra) (S. chartarum) and its toxigenic metabolites (satratoxins), and
      to study laboratory parameters or biomarkers related to allergic or toxic human
      health effects. Exposure characterization and quantification were performed using
      microscopic, culture, and chemical techniques. The study population (n = 53)
      consisted of 39 female and 14 male employees (mean age 34.8 years) who had worked
      for a mean of 3.1 years at a problem office site; a control group comprised 21
      persons (mean age 37.5 years) without contact with the problem office site.
      Health complaints were surveyed with a 187-item standardized questionnaire. A
      comprehensive test battery was used to study the red and white blood cell system,
      serum chemistry, immunology/antibodies, lymphocyte enumeration and function.
      Widespread fungal contamination of water-damaged, primarily cellulose material
      with S. chartarum was found. S. chartarum produced a macrocyclic trichothecene,
      satratoxin H, and spirocyclic lactones. Strong associations with exposure
      indicators and significant differences between employees (n = 53) and controls (n
      = 21) were found for lower respiratory system symptoms, dermatological symptoms,
      eye symptoms, constitutional symptoms, chronic fatigue symptoms and several
      enumeration and function laboratory tests, mainly of the white blood cell system.
      The proportion of mature T-lymphocyte cells (CD3%) was lower in employees than in
      controls, and regression analyses showed significantly lower CD3% among those
      reporting a history of upper respiratory infections. Specific S. chartarum
      antibody tests (IgE and IgG) showed small differences (NS). It is concluded that
      prolonged and intense exposure to toxigenic S. chartarum and other atypical fungi
      was associated with reported disorders of the respiratory and central nervous
      systems, reported disorders of the mucous membranes and a few parameters
      pertaining to the cellular and humoral immune system, suggesting a possible
      immune competency dysfunction.

PMID- 8738350
TI  - Otoneurological study in workers exposed to styrene in the fiberglass industry.
AB  - Twenty workers exposed to styrene and acetone in small fiberglass factories were
      monitored for 8 h using passive dosimeters. Urine samples were collected at the
      end of the workshift and before the start of work on the next morning. The 8-h
      time-weighted average exposure values for styrene and acetone ranged from 14 to
      416 mg/m3 and from 70 to 277 mg/m3, respectively. The sum of styrene metabolites,
      mandelic acid and phenylglyoxylic acid (MA + PGA), in the next-morning urine
      samples ranged from 81 to 943 mg/g creatinine. Different test sensitivity was
      identified in the otoneurological battery: it was low for audiometric tests and
      ABR, and relatively high for vestibular tests. The vestibular system seems
      partially sensitive to the toxic effects of styrene in the absence of clinical
      signs and symptoms. The actual exposure levels for styrene cannot be considered
      devoid of functional subclinical consequences.

PMID- 8738351
TI  - Investigation of a cluster of ten cases of Hodgkin's disease in an occupational
      setting.
AB  - The objective of this study was to identify occupational exposures that might be
      etiologically linked to an unusual cluster of ten cases of Hodgkin's disease. The
      cases were identified within the active workforce of a large chemical
      manufacturing firm over a 23-year period by the medical director of the
      facilities. Based on comparison with regional cancer incidence rates, the
      standardized incidence ratio for Hodgkin's disease was 497 (95% confidence
      interval: 238-915) for the period from the construction of the facilities in 1966
      through early 1992. A nested case-control study was undertaken with 200 controls
      selected according to case-cohort sampling. Simultaneously, efforts were
      initiated to confirm and characterize each case more fully. Occupational
      exposures were identified and categorized using process, work history, medical
      record, and industrial hygiene data. Tissue slides were available for eight cases
      and a second review confirmed the diagnosis of Hodgkin's disease. For one case, a
      final diagnosis of large-cell anaplastic lymphoma was determined after histology
      review. Among 214 different chemical agents studied, eight were identified to
      which three or more of the cases had been exposed prior to the date of their
      initial diagnosis. Exposure odds ratios were statistically elevated for five of
      these agents; dose-response evaluations for two of the agents, ethylene oxide and
      benzene, failed to provide additional support for a causal relationship. In
      conclusion, although several statistical associations were identified, no
      substance emerged as a likely candidate for explaining the observed Hodgkin's
      disease cluster.

PMID- 8738352
TI  - Hydrocarbon exposure and chronic renal disease.
AB  - The study objective was to investigate further the potential role of long-term
      exposure to hydrocarbons (HCs) in the development of idiopathic chronic
      glomerulopathy (ICG) using a more refined measurement of HC exposure. A total of
      321 pairs of cases and controls, matched by age, gender, and geographical area,
      were assembled. A detailed questionnaire was blindly administered to cases and
      controls to collect information on occupational and medical history and
      sociodemographic data. By integrating quantified measurements of HC exposure from
      a variety of sources with each subject's occupational history, a lifetime HC
      exposure score could be estimated and expressed in parts per million (ppm). Cases
      had an hydrocarbon exposure mean score of 165 ppm (median 48 ppm) as compared to
      162 ppm (median 43 ppm) for controls (P = 0.757). When using hydrocarbon exposure
      as a dichotomous variable with a cutoff point at 100 ppm, cases had a higher
      proportion of exposed than controls, but the difference was not statistically
      significant at the 0.05 level, even after controlling for possible confounders
      through logistic regression. Subgroup analyses showed mixed results. In most
      subgroups differences between cases and controls tended to become significant
      when hydrocarbon was used as a dichotomous variable. Results from this study do
      not sufficiently support the hypothesized association of HC exposure and ICG in
      general. Subgroup analyses need further investigations. Efforts to generate
      accurate estimates of lifetime HC exposure should be emphasized for future
      investigations.

PMID- 8738353
TI  - Different acute effects of single-axis and multi-axis hand-arm vibration.
AB  - Under laboratory conditions the effects of single-axis and multi-axis hand-arm
      vibration exposure on several strain parameters were tested in up to 20 male
      subjects. As parameters of these acute effects, the biodynamic vibration behavior
      of the hand-arm system, the electrical activity of the most affected muscle
      groups, the skin temperature, the vibration sensitivity of the fingertips, and
      the subjective vibration sensation were measured. When comparing simulated three
      axis vibration exposure with single-axis vibration exposure, synergistic effects
      in the form of an increasing reaction could be found. It could be proven that the
      vector sum of the frequency-weighted acceleration in the three axes represents
      the acute effects better than does the weighted acceleration in the main axis
      alone. This summation has to take into account the relatively lower effects of
      vibration in the x- or y-direction compared with the z-direction. On the basis of
      the experimental results a new proposal for frequency weighting of the three
      different axes and an energetic summation procedure are derived. Application of
      this knowledge in the International Standard ISO 5349 is proposed.

PMID- 8738354
TI  - Airflow obstruction in chalkpowder and sugar workers.
AB  - Our aim was to investigate the relationship between suspected occupational
      hazards and airflow obstruction in industrial workers. The study was a cross
      sectional survey of 314 male workers from a chalkpowder plant (n = 158) and from
      a sugar refinery (n = 156). Occupational exposure to chalkpowder and sugar dust
      was assessed by individual job classification. Outcome variables included
      respiratory symptoms and routine spirometric parameters. Statistical analysis was
      done for each industry separately. Overall, mean pulmonary function parameters
      fell either within or above the normal range in both industries. However,
      analysis by job classification showed that in the chalkpowder plant, all indices
      of airway obstruction declined significantly with increasing dustiness.
      Additionally, workers in the dustiest workplace (chalk sacking) had significantly
      lower airflow parameters than workers from other workstations. In the sugar
      refinery, workers exposed to sugar dust in the sugar cube manufacture workstation
      had significantly lower forced expiratory volume in 1 s (FEV1) (p = 0.02) than
      the non-exposed ones. For both industries, the proportion of subjects complaining
      of cough and/or phlegm was greater among the most exposed subgroups than among
      the remaining workers but the differences were not statistically significant. In
      conclusion, coupling spirometry to job classification proved useful in disclosing
      a relationship between airflow obstruction and exposure to either chalkpowder or
      sugar dust in industrial workers.

PMID- 8738355
TI  - Evaluation and classification of high-resolution computed tomographic findings in
      patients with pneumoconiosis.
AB  - The standard ILO classification for pneumoconiotic changes using conventional X
      ray films has become well established. In recent years computed tomography has
      played an increasing role in occupational medicine and above all in the
      assessment of pneumoconiosis. Therefore a standardised method of classification
      for CT also seems necessary. A system of classification developed by occupational
      hygienists and radiologists allows a detailed description of parenchymal and
      pleural changes and the use of 28 additional symbols. Furthermore, special
      diagnoses relevant to occupational medicine and additional comments can be made.
      The classification system was tested in practice in the research project "Early
      diagnosis of asbestos-related diseases" (Fruhdiagnostik asbestverursachter
      Erkrankungen). It was shown to be both practicable and easily reproducible, intra
      individually and interindividually.

PMID- 8738356
TI  - The temporary threshold shift of vibratory sensation induced by composite-band
      vibration exposure.
AB  - Eight healthy subjects were exposed to three 1/3 octave-band vibrations (63, 200,
      and 500 Hz) by hand clasping a vibrated handle in a soundproof and
      thermoregulated room. The vibratory sensation threshold at 125 Hz was measured
      before and after the vibration exposure at an exposed fingertip. According to a
      preceding study, we first determined the relationship between the acceleration of
      the vibration and the temporary threshold shift of vibratory sensation
      immediately after the vibratory exposure (TTSv,0) induced by 1/3 octave-band
      vibration. We then measured TTSv after the exposure to a composite vibration
      composed of two 1/3 octave-band vibrations that might induce an equal magnitude
      of TTSv,0 on the basis of the above relationship. The TTSv,0 induced by the
      composite vibration was not larger than the TTSv,0 induced by the component
      vibrations. This result suggests that the component of the vibration inducing the
      largest TTSv,0 determines the TTSv,0 by broad-band random vibration.

PMID- 8738357
TI  - On-line monitoring of benzene air concentrations while driving in traffic by
      means of isotopic dilution gas chromatography/mass spectrometry.
AB  - There is no shortage of information about the average benzene concentrations in
      urban air, but there is very little about microenvironmental exposure, such as in
      vehicle concentrations while driving in various traffic conditions, while
      refuelling, or while in a parking garage. The main reason for this lack of data
      is that no analytical instrumentation has been available to measure on-line trace
      amounts of benzene in such situations. We have recently proposed a highly
      accurate, high-speed cryofocusing gas chromatography/mass spectrometry (GC/MS)
      system for monitoring benzene concentrations in air. Accuracy of the analytical
      data is achieved by enrichment of the air sample before trapping, with a stable
      isotope permeation tube system. The same principles have been applied to a new
      instrument, specifically designed for operation on an electric vehicle (Ducato
      Elettra, Fiat). The zero emission vehicle and the fully transportable, battery
      operated GC/MS system provide a unique possibility of monitoring benzene exposure
      in real everyday situations such as while driving, refuelling, or repairing a
      car. All power consumptions have been reduced so as to achieve a battery-operated
      GC/MS system. Liquid nitrogen cryofocusing has been replaced by a packed,
      inductively heated, graphitized charcoal microtrap. The instrument has been
      mounted on shock absorbers and installed in the van. The whole system has been
      tested in both fixed and mobile conditions. The maximum monitoring period without
      external power supply is 6 h. The full analytical cycle is 4 min, allowing close
      to real-time monitoring, and the minimum detectable level is 1 microgram/m3 for
      benzene. In-vehicle monitoring showed that, when recirculation was off and
      ventilation on, i.e., air from outside the vehicle was blown inside,
      concentrations varied widely in different driving conditions: moving from a
      parking lot into normal traffic on an urban traffic condition roadway yielded an
      increase in benzene concentration from 17 to 62.3 micrograms/m3 even if the
      actual distance was small. A larger increase was observed when a car was left
      with the engine running at a distance 2 m from the zero emission vehicle: We
      measured an increment of benzene concentrations from 15.2 to 174.4 micrograms/m3
      with a car equipped with a catalytic converter, and from 19.1 to 386.3
      micrograms/m3 with a car without such a converter.

PMID- 8738358
TI  - Airborne emissions at skin surfaces: a potential biological exposure index.
AB  - Dermal exposures of methanol were administered in a clinical study designed to
      compare several biological indicators. Four subjects were exposed in five
      exposure sessions of varying length. In each session, a sequence of measurements
      of methanol concentrations in blood, breath, and headspace samples of air at
      exposed and unexposed skin were collected before and after dermal exposures. Skin
      headspace samples, collected in gas sampling bags, were designed to reflect
      equilibrium skin: air partitioning. At exposed skin, headspace samples were
      highly elevated for at least 8 h following exposure, indicating the presence of a
      methanol reservoir in skin. After exposure, methanol concentrations at exposed
      skin showed a rapid initial decline, then a slower first-order decrease. Methanol
      concentrations were clearly detectable in headspace samples at unexposed skin.
      Substantial transfer from exposed skin occurred due to mechanical contact and
      washing. When transfer was restricted, surface concentrations at unexposed skin
      were similar to levels in breath and were strongly correlated to methanol
      concentrations in blood. While results are preliminary due to the small sample
      sizes and several unresolved experimental issues, the simple, rapid, and
      noninvasive skin headspace measurements appear useful as a biological exposure
      indicator that clearly shows the presence and site of a dermal exposure, and
      measurements at unexposed skin reflect concentrations in blood.

PMID- 8738359
TI  - Diagnosis of carotid-cavernous fistulas with magnetic resonance angiography-
      demonstrating the draining veins utilizing 3-D time-of-flight and 3-D phase
      contrast techniques.
AB  - This study assessed the ability to diagnose carotid-cavernous fistulas (CCFs) non
      invasively using magnetic resonance angiography (MRA). Both three-dimensional
      time-of-flight (3-D TOF) MRA and three-dimensional phase-contrast (3-D PC) MRA
      were compared with conventional cerebral angiography in nine patients with CCFs.
      CCFs were grouped according to Barrow's classification. In all cases, 3-D TOF MRA
      revealed an inferior petrosal sinus as a draining vein. 3-D PC MRA demonstrated a
      dilated and tortuous superior ophthalmic vein (SOV) and reflux of the SOV in
      seven patients. In conclusion, CCFs can be diagnosed with MRA alone by
      demonstrating the drainging veins.

PMID- 8738360
TI  - Pleomorphic xanthoastrocytoma: some observations.
AB  - The authors describe 3 cases of cerebral pleomorphic xanthoastrocytoma, one of
      which has an unusual neuroradiological appearance, and review the clinical and
      prognostic features of the 96 cases reported in the literature. Pleomorphic
      xanthoastrocytoma is a neuroectodermal tumor that affects young patients, in a
      superficial or supratentorial site, most frequently at the temporal level. It is
      difficult to formulate a differential diagnosis with other neuroectodermal tumors
      or with meningioma on the basis et neuroradiological appearance, as demonstrated
      by one of the cases reported here. The prognosis of this tumor is very good,
      regardless of the type of treatment performed, although both relapse and, more
      rarely, malignant tumor evolution are possible.

PMID- 8738361
TI  - Biomechanical studies of transthoracic vertebral body replacement with autologous
      bone grafts (fibula and rib).
AB  - Thoracic processes which destroy vertebral bodies leave gaps which usually have
      to be bridged. The aim of our experiments was to find out whether rib and fibula
      grafts are suitable vertebral body substitutes from the biomechanical point of
      view. Therefore, we examined characteristics of vertebral body/bone
      graft/vertebral body arrangements under the influence of pulsating compression
      forces in a testing machine. The deformation of the rib graft alone was 0.78 mm
      under a preselected peak load of 1010 Newton. When the rib graft was placed
      between two vertebral bodies, the deformation (creeping) was 6 mm under a peak
      load of 1010 Newton. The deformation of the fibula graft alone was 0.41 mm, and
      when placed between vertebral bodies maximally 3 mm. The results of our
      experiments lead to the conclusion that ribs modified according to our design are
      prinzipally suitable for vertebral body replacement in the thoracic region as far
      as primary stress resistance is concerned. Characteristics of these bone grafts
      in the human body are being followed-up.

PMID- 8738362
TI  - The role of adjuvant radiation and multiple resection within the surgical
      management of brain metastases.
AB  - Cerebral metastases occur in 25% to 35% of all cancer patients. The advances in
      systemic and topical treatment as well as the rising incidence of lung cancer and
      melanomas are associated with an increasing incidence of cerebral metastases.
      More than 20,000 patients die every year in the Federal Republic of Germany of
      this disease. This retrospective analysis covers 145 patients who underwent
      surgery. Survival analysis of different subgroups was performed. The patients
      were grouped according to their clinical status and the different therapeutical
      procedures which were performed. Group A, consisting of all those patients where
      a gross total resection could be performed and where no systemic disease was
      apparent at the time of craniotomy showed the best results, having the highest
      portion of long term survivors. Group B, consisting of those patients who
      underwent a subtotal resection and who had no systemic disease at the time of
      craniotomy, had a worse outcome. Group C patients (gross total resection and
      systemic disease) as well as Group D (subtotal resection and systemic disease)
      presented the poorest results with respect to survival. A benefit was mediated by
      adjuvant radiation as well as multiple resections. Surgery is the method of
      choice for the treatment of a single metastasis. Advances in microsurgery
      nowadays sometimes justify even the removal of multiple metastases, depending on
      their location, on the general condition of the patient and on prognosis.

PMID- 8738363
TI  - Effect of dexamethasone, barbiturate and hypothermy on edema induced by CO2 laser
      brain lesion in the dog: light and electron microscopic study.
AB  - Experiments were carried out to compare the effectiveness of dexamethasone, a
      barbiturate, and hypothermy on experimental cerebral edema caused by CO2 laser in
      dogs. Experimental brain lesions were created over the right frontal cortex of
      the dogs through the intact dura mater with CO2 laser energy (40 W impact, 0.5
      second duration, for a total time of 4 seconds on a 12.5 mm surface). Animals
      were divided into four groups and treated with dexamethasone, a barbiturate,
      hypothermy, and a crystalloid (control group). The brains were examined 48 hours
      after injury. Histologically all brain lesions showed three distinct layers with
      a vaporized center bordered by a zone of coagulation necrosis surrounded by
      edema. The main finding in the surrounding coagulation and edematous layers was
      dilatation of the vessels. Hemorrhage was sometimes observed mainly in the
      edematous layer. The effect of these therapies on the laser lesion and the
      effectiveness of these therapies on surrounding cerebral edema were evaluated by
      both light and electron microscopy. The control group showed significantly
      greater edema than the dexamethasone group. There was only a minimal difference
      between the control group and the barbiturate group, and there was no significant
      difference in amount of edema between control group and the hypothermy group.
      There was less edema in the dexamethasone group than in the other ones. These
      data suggest that dexamethasone inhibits edema in CO2 laser lesions with the same
      efficacy as shown in the treatment of vasogenic edema.

PMID- 8738364
TI  - Spinal meningeal melanocytoma. Case report and analysis of diagnostic criteria.
AB  - A case of cervical juxtamedullary meningeal melanocytoma is presented along with
      results of careful neuroradiological and pathological examinations. The authors
      review the previous literature and discuss the problems related to the intriguing
      diagnosis of this very rare entity. CT and MRI show variable appearances due to
      different degrees of melanization and do not reliably allow us to distinguish
      meningeal melanocytomas from other pigmented tumors. Pathological examination of
      the tumor is critical for diagnosis, but it absolutely must comprise electron
      microscopy and immunohistochemistry. Immunohistochemical and ultrastructural
      criteria are thus proposed to distinguish meningeal melanocytoma from pigmented
      meningioma or schwannoma and malignant melanoma (primary or secondary).

PMID- 8738365
TI  - Isolated trigeminal neuralgia secondary to distal anterior inferior cerebellar
      artery aneurysm.
AB  - A 43-year-old woman complaining of severe pain of the right side of the face was
      admitted to the Department of Neurosurgery. It had been present for three months
      and diagnosed as trigeminal neuralgia. The CT scan without contrast material had
      been considered normal at that time. Three months later, after a favourable
      response to carbamazepine, she suddenly developed right occipital headache and
      drowsiness. On admission, she was alert, and neurological examination revealed
      only mild neck stiffness. Computed tomographic scan demonstrated an acute
      hematoma in the right cerebellopontine angle and in the fourth ventricle.
      Vertebral angiography revealed an aneurysm of the right anterior inferior
      cerebellar artery (AICA). A posterior fossa approach disclosed a large, nearly
      totally thrombosed, saccular AICA aneurysm, which showed minimal compression to
      the pons at the trigeminal root entry zone. The aneurysm was clipped and excised.
      She showed an excellent recovery and was free of pain in the early postoperative
      period and at the last examination 16 months later. Aneurysms in the distal AICA
      are very rare lesions. Only 31 cases have been published so far. Distal AICA
      aneurysm in an extremely unusual cause of trigeminal neuralgia secondary to
      aneurysmal compression. The literature concerning AICA aneurysms and their
      clinical manifestations is reviewed and discussed.

PMID- 8738366
TI  - Cerebro-vasculopathy and malignancy: catastrophic complications of radiotherapy
      for optic nerve glioma in a von Recklinghausen neurofibromatosis patient.
AB  - The authors report a unique case of a patient with intraorbital optic nerve
      glioma and von Recklinghausen neurofibromatosis who developed cerebro
      vasculopathy and malignant transformation in the orbit 18 months after
      radiotherapy treatment. The case is an important reminder of the possibly
      increased susceptibility of von Recklinghausen neurofibromatosis patients to the
      complications of radiotherapy.

PMID- 8738367
TI  - Intracranial arterial aneurysm complicating Behcet's disease.
AB  - Behcet's disease, a rare condition in central Europe but more common in Turkey
      where it was originally described, is characterized clinically by the presence of
      a diagnostic triad of oral and genital aphthous ulcers, meningitis, and relapsing
      iridocyclitis. Vascular lesions including arterial and venous occlusions,
      arterial aneurysms and varices are one of the common complications of Behcet's
      disease occur most commonly in the abdominal aorta, femoral arteries and
      pulmonary arteries. There have been only four reports of aneurysms of cerebral
      arteries in the literature. The authors describe a patient with Behcet's disease
      who suffered secondary subarachnoid hemorrhage due to a ruptured aneurysm of the
      anterior communicating artery 3 years after the initial diagnosis. This case
      report draws further attention to this rare entity in patients with Behcet's
      disease.

PMID- 8738368
TI  - Aneurysm of an azygos anterior cerebral artery: report of two cases and review of
      the literature.
AB  - Aneurysm of an azygos anterior cerebral artery is rare. Two cases are presented.
      In case 2, the coexistence of arachnoid cyst with this aneurysm is reported.
      Literature is reviewed.

PMID- 8738369
TI  - Nociceptive neurones in rat superior colliculus. I. Antidromic activation from
      the contralateral predorsal bundle.
AB  - Accumulating evidence suggests that the rodent superior colliculus (SC) plays as
      important a role in avoidance and defensive behaviours as it does in orientation
      and approach. These two complementary behaviours are associated with two
      anatomically segregated tectofugal output pathways, such that orientation and
      approach are mediated by the crossed descending projection, whereas avoidance and
      defence are subserved via the uncrossed projection. Because nociceptive neurones
      in the SC have been presumed to participate in withdrawal or defensive
      behaviours, it has been proposed that they have direct access only to the
      uncrossed efferent pathway. However, in certain behavioural situations, the most
      adaptive response to injury, or to a painful object in prolonged contact with the
      skin, is to orient towards the source of discomfort so that the skin can be
      licked and/or the offending object removed. Presumably then, nociceptive as well
      as low-threshold neurones would have access to the crossed descending pathway in
      order to initiate such behaviours. Determining whether or not this is the case
      was the objective of the present study. Both nociceptive-specific (82%) and wide
      dynamic-range (18%) SC neurones were identified using long-duration (up to 6 s),
      frankly noxious mechanical and thermal stimuli in urethane-anaesthetised Long
      Evans hooded rats. The majority (85.7%) of the nociceptive neurones encountered
      were located within the intermediate layers, which corresponds with the location
      of the cells-of-origin of the crossed descending projection. Nearly half (44.9%)
      were activated antidromically from electrical stimulation of the crossed
      descending pathway at a site in the brainstem below its decussation. The mean
      conduction velocity of these nociceptive output neurones was 9.02 m/s, which
      corresponds well to previous estimates of conduction velocity in the crossed
      tecto-reticulo-spinal tract. These data demonstrate that a significant proportion
      of nociceptive neurones in the rat SC have axons that project to the
      contralateral brainstem via the crossed descending projection. Nociceptive
      neurones could, therefore, effect orientation responses to noxious stimuli via
      similar output pathways that low-threshold neurones utilize to initiate
      orientation to innocuous stimuli.

PMID- 8738370
TI  - Nociceptive neurones in rat superior colliculus. II. Effects of lesions to the
      contralateral descending output pathway on nocifensive behaviours.
AB  - A wealth of evidence implicates the crossed descending projection from the
      superior colliculus (SC) in orientation and approach behaviours directed towards
      novel, non-noxious stimuli. In our preceding paper, we identified a population of
      nociceptive neurones in the rat SC that have axons that project to the
      contralateral brainstem via this output pathway. The purpose of the present study
      was, therefore, to evaluate the prediction that the crossed descending projection
      of the SC is also involved in the control of orientation and approach movements
      of the head and mouth made during the localisation of persistent noxious stimuli.
      An independent-groups design was used to test the effects of interrupting the
      contralateral descending projection from the SC on the behavioural reactions
      elicited by noxious mechanical stimuli presented to the tail and hindpaws. In
      different groups of animals, a microwire knife was used to cut the contralateral
      descending fibres at two different locations: (1) a sagittal cut at the level of
      the dorsal tegmental decussation; (2) a bilateral coronal cut of the predorsal
      bundle at the level of the medial pontine reticular formation. Retrograde
      anatomical tracing techniques were then used to evaluate the effectiveness of the
      cuts and to assess possible involvement of non-collicular fibre systems in both
      lesioned and control animals. Additional behavioural procedures were performed to
      test for general neurological status and responsiveness of animals to non-noxious
      stimuli. Anatomical tracing data indicated that the largest population of
      neurones with fibres severed by both cuts were the cells-of-origin of the
      contralateral descending projection in the intermediate white layer of the SC.
      Behavioural results showed that significantly more animals in both lesion groups
      failed to locate and bite a mechanical clip placed on the tail. Instead of
      switching to motor behaviours to localise and remove noxious stimuli, they
      persisted with defensive reactions, which included freezing, vocalisation or
      forward and backward escape. In contrast, when the clip was placed on the
      hindpaws, it was successfully localised by most lesioned and control animals;
      however, lesioned animals had reliably longer latencies and spent less time in
      close contact with the clip. Consistent with the established role of the
      contralateral descending projection in non-noxious orientation, lesioned animals
      also showed orienting deficits to a range of non-noxious sensory stimuli. These
      data suggest that, under certain behavioural circumstances, nociceptive
      information from the SC is integral to the elaboration of orienting and approach
      movements of the head and mouth elicited by persistent noxious stimuli.

PMID- 8738371
TI  - Afferents to the seizure-sensitive neurons in layer III of the medial entorhinal
      area: a tracing study in the rat.
AB  - Neurons in layer III of the medial entorhinal area (MEA) in the rat are extremely
      vulnerable to local injections of amino-oxyacetic acid and to experimentally
      induced limbic seizures. A comparable specific pathology has been noted in
      surgical specimens from patients with temporal lobe epilepsy. Efforts to
      understand this preferential neuronal vulnerability led us to study the neural
      input to this layer in the rat. Iontophoretic injection of the retrograde tracer
      fast blue, aimed at layer III of the MEA, resulted in retrogradely labeled
      neurons in the presubiculum in all the injected hemispheres. The nucleus reuniens
      thalami, the anteromedial thalamic nucleus, the ventral portion of the claustrum
      (endopiriform nucleus), the dorsomedial parts of the anteroventral thalamic
      nucleus, and the septum-diagonal band complex were labeled less frequently. In
      only one experiment, retrogradely labeled neurons were observed in the
      ventrolateral hypothalamus and in the brainstem nucleus raphe dorsalis. Since
      projections from claustrum to the entorhinal cortex has not been studied in the
      rat with modern sensitive anterograde tracing techniques, iontophoretic
      injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin were
      placed into the ventral portion of the claustrum. Anterogradely labeled fibers in
      the entorhinal area proved not to be confined to the MEA, since a prominent
      projection distributed to the lateral entorhinal area as well. In both areas, the
      densest terminal labeling was present in layers IV-VI, whereas layer III appeared
      to be only sparsely labeled. The present data indicate that of all potential
      afferents only those from the presubiculum distribute preferentially to layer III
      of the MEA. This, in turn, suggests a potentially important role of the
      presubiculum in the seizure-related degeneration of neurons in layer III of the
      MEA.

PMID- 8738372
TI  - Reevaluation of synaptic relationships of cerebellar terminals in the ventral
      lateral nucleus of the rhesus monkey thalamus based on serial section analysis
      and three-dimensional reconstruction.
AB  - Terminals of cerebellar afferents (CB) to different regions of the ventral
      lateral nucleus (VL) of the rhesus monkey thalamus were labeled with wheat germ
      agglutinin-horseradish peroxidase following injections into the dentate nucleus.
      Synaptic relationships of 17 CB with projection neuron dendrites (PNd) and local
      circuit neuron dendrites (LCNd) were analyzed in serial ultrathin sections from
      dorsal and ventral VL regions, which are known to differ cytoarchitecturally and
      functionally. Three terminals were reconstructed using three-dimensional (3D)
      computer image analysis techniques to obtain volumetric and planar measurements.
      CB in the ventral VL were often flat and elongated with synaptic vesicles
      arranged in clusters. Each CB was engaged with one PNd and one to four LCNd. A
      single bouton formed 8-50 synaptic contacts, with those on PNd outnumbering the
      ones on LCNd 4.1:1. Only some CB in the ventral VL were engaged in complex
      synaptic arrangements such as triads and serial synapses. Most CB in the dorsal
      VL displayed a roundish shape and numerous uniformly distributed synaptic
      vesicles. They formed 5-25 synaptic contacts with a 3:1 ratio of contacts on PNd
      compared with those on LCNd. CB in the dorsal VL participated in a variety of
      complex synaptic arrangements. Two types of triads were found: classic with CB,
      PNd and LCNd, and unconventional with CB and two LCNd. CB were also involved in
      serial synapses with two LCNd or LCNd and another PNd, and serial sequential
      synapses with two LCNd and a PNd. Three glomerulus-like structures were
      encountered in the dorsal VL. 3D reconstruction and volumetric measurements
      revealed that synaptic contacts formed by CB on PNd had varying shapes and sizes
      (0.022-0.274 microns2). Synapses formed on LCNd were larger (0.09-0.407
      microns2). The total area of all active zones of a single CB on LCNd was either
      equal to or about 40% smaller than that of synapses on PNd. The entire active
      zone area comprised 1-1.6% of the total CB surface area and did not seem to
      correlate with the volume. Synaptic contacts formed by associated LCNd on PNd in
      complex arrangements were usually small (0.021-0.044 micron2). The results
      suggest that: synapses formed by CB on PNd and LCNd, and synapses formed by LCNd
      on PNd may differ in strength; a variety of different circuits participate in the
      processing of cerebellar afferent information in the primate VL; and these
      circuits differ in functionally different VL subdivisions.

PMID- 8738373
TI  - Contribution of somatosensory cortex to responses in the rat cerebellar granule
      cell layer following peripheral tactile stimulation.
AB  - The spatial coincidence of somatosensory cerebral cortex (SI) and trigeminal
      projections to the cerebellar hemisphere has been previously demonstrated. In
      this paper we describe the temporal relationship between tactilely-evoked
      responses in SI and in the granule cell layer of the cerebellar hemisphere, in
      anesthetized rats. We simultaneously recorded field potentials in areas of common
      receptive fields of SI and of the cerebellar folium crus IIa after peripheral
      tactile stimulation of the corresponding facial area. Response of the cerebellar
      granule cell layer to a brief tactile stimulation consisted of two components at
      different latencies. We found a strong correlation between the latency of the SI
      response and that of the second (long-latency) cerebellar component following
      facial stimulation. No such relationship was found between the latency of the SI
      response and that of the first (short-latency) cerebellar component, originating
      from a direct trigeminocerebellar pathway. In addition, lidocaine pressure
      injection in SI, cortical ablation, and decerebration all significantly affected
      the second cerebellar peak but not the first. Further, when tactile stimuli were
      presented 75 ms apart, the response in SI failed, as did the second cerebellar
      peak, while the short-latency cerebellar response still occurred. We found a wide
      spatial distribution of the upper lip response beyond the upper lip area in crus
      IIa for the long-latency component of the cerebellar response. Our results
      demonstrate that SI is the primary contributor to the cerebellar long-latency
      response to peripheral tactile stimulation. These results are discussed in the
      context of Purkinje cell responses to tactile input.

PMID- 8738374
TI  - An immunocytochemical study of glutamate receptors and glutamine synthetase in
      the hippocampus of rats injected with kainate.
AB  - Immunocytochemistry was used to study the distribution of the kainate receptors
      GluR1, GluR2/3 and GluR4 and of the N-methyl-D-aspartate (NMDA) receptor NMDAR1
      as well as the astrocyte markers glutamine synthetase (GS) and glial fibrillary
      acidic protein (GFAP) in the hippocampus of normal and kainate-lesioned rats.
      Hippocampal pyramidal neurons and dentate granule neurons were labelled heavily
      for GluR1 and GluR2/3, but only lightly for GluR4. Dense GluR4 immunopositivity
      was, however, observed in oligodendrocyte-like glial cells. Hippocampal pyramidal
      neurons and dentate granule neurons were moderately labelled for NMDAR1.
      Intravenous kainate injections resulted in a decrease in GluR1 and GluR2/3
      immunoreactivity on the apical dendrites of pyramidal neurons as early as 7 h
      postinjection. At 18 h, there was a marked reduction in GluR1 and GluR2/3
      receptors in the terminal tuft of dendrites of most hippocampal pyramidal neurons
      in the affected area, although some cells showed labelling in other portions of
      the apical dendrites and in basal dendrites. Immunostaining for GluR4 and NMDAR1
      was also reduced at this time. At postinjection day 3, only the cell bodies and
      the basal dendrites of a few scattered pyramidal cells were labelled. Taken
      together, these results indicate a progressive loss of glutamate receptors, which
      affects the apical dendritic tree before the basal dendritic tree. The decrease
      in receptor immunoreactivity could be due to a downregulation of the receptors,
      since it occurred as early as 7 h postlesion, before cell death was evident in
      Nissl-stained sections. At long intervals after kainate injection, all pyramidal
      cells at the centre of the lesion showed a lack of glutamate receptor staining,
      and no partially labelled pyramidal cells were observed. The periphery of the
      lesion, however, contained many partially labelled pyramidal neurons among the
      unlabelled cells and had features of early lesions. The present study also showed
      an early decrease in GS immunoreactivity in the affected CA fields of the
      hippocampus (18 h to 3 days postinjection), followed by a medium-term increase (5
      68 days) and a late decrease in GS immunoreactivity (81 days). The decrease in GS
      immunoreactivity at 81 days is not due to an absence of astrocytes, since GFAP
      staining showed many densely labelled astrocytes in the affected CA field.

PMID- 8738375
TI  - Haloperidol-increased muscle tone in rats as a model of parkinsonian rigidity.
AB  - The aim of the present study was to find out whether haloperidol-induced rigidity
      was similar to that seen in parkinsonism. Simultaneous measurements of the muscle
      resistance (mechanomyogram, MMG) of the hind foot to passive flexion and
      extension in the ankle joint, as well as determination of the electromyographic
      (EMG) activity of the gastrocnemius and tibialis anterior muscles of rats were
      carried out. Haloperidol was injected in doses of 0.5-10 mg/kg 1 h before the
      start of measurements. Haloperidol increased, in a dose-dependent manner, the
      muscle resistance of the rat's hind leg to passive movements. Muscle rigidity was
      accompanied with an increase resting, as well as in the stretch-induced long
      latency EMG activity (in which supraspinal reflexes are most probably involved)
      in both those muscles, whereas the short-latency EMG activity (first large bursts
      of EMG activity, beginning ca. 9 ms after the start of a movement, probably of a
      spinal origin) was significantly decreased. The obtained results suggest that the
      haloperidol-increased MMG/EMG activity might be a good model of parkinsonian
      rigidity.

PMID- 8738376
TI  - Disynaptic vestibulospinal and reticulospinal excitation in cat lumbosacral
      motoneurons: modulation during fictive locomotion.
AB  - This study compares some characteristics of the disynaptic excitatory pathways
      from the lateral vestibular nucleus (LVN) and medial longitudinal fasciculus
      (MLF) to lumbosacral alpha-motoneurons in the decerebrate cat. We used the
      spatial facilitation technique to test whether disynaptic LVN and MLF excitatory
      postsynaptic potentials (EPSPs) are produced by common last-order interneurons in
      the lumbosacral segments of the spinal cord. Of 77 motoneurons examined, 26
      exhibited disynaptic EPSPs from both supraspinal sources. No spatial facilitation
      was found between LVN and MLF EPSPs in 21 of 24 cells that were adequately
      tested. In 3 of 23 cells (all flexor motoneurons), some spatial facilitation was
      found in some but not all trials. These observations suggest that stimulation of
      the LVN and MLF produces disynaptic EPSPs in motoneurons through largely separate
      populations of last-order interneurons. Disynaptic MLF and LVN EPSPs showed
      parallel patterns of modulation during fictive locomotion. Maximal disynaptic
      EPSP amplitudes occurred during the phase of the step cycle when the recorded
      motoneuron, whether flexor or extensor, exhibited depolarizing locomotor drive
      potentials and the corresponding muscle nerve was active. These observations,
      taken together, suggest that disynaptic LVN and MLF EPSPs are produced in
      motoneurons by at least four separate populations of segmental last-order
      excitatory interneurons, with separate populations projecting to flexor versus
      extensor cells. The results also suggest that the modulation of the disynaptic
      EPSPs during fictive locomotion is mainly due to premotoneuronal convergence of
      input from the respective descending systems and from the segmental central
      pattern generator for locomotion onto common interneurons.

PMID- 8738378
TI  - The three-dimensional human vestibulo-ocular reflex: response to long-duration
      yaw angular accelerations.
AB  - We recorded three-dimensional eye movements during angular acceleration steps
      from 0 to 250 degrees/s at 20 degrees/s2 about an earth-vertical axis.
      Experiments were performed on 27 normal subjects and on 19 patients who had
      recovered well from unilateral vestibular deafferentation on the right or left
      side. In addition to compensatory horizontal eye movements, significant vertical
      and torsional eye movement components were elicited. These vertical and torsional
      eye velocity traces led to a shift of the axis of eye velocity away from the axis
      of head velocity. Horizontal, vertical, and torsional velocity components showed
      clear differences between normals and patients with unilateral vestibular
      deafferentation. In normals, the axis of eye velocity tilted backward and
      slightly away from the axis of head velocity. Patients showed similar, but more
      pronounced, shifts during rotations toward the intact ear and shifts in the
      opposite direction for rotations toward the operated ear. Eye velocity traces
      were analyzed with special consideration given to the orientation of the axis of
      eye velocity. We speculate that the vertical and torsional velocity components
      may be due to the effects of Listing's plane, as well as the contributions of the
      otolith signals.

PMID- 8738377
TI  - Directional organization of eye movement and visual signals in the floccular lobe
      of the monkey cerebellum.
AB  - The floccular lobe of the monkey is critical for the generation of visually
      guided smooth eye movements. The present experiments reveal physiological
      correlates of the directional organization in the primate floccular lobe by
      examining the selectivity for direction of eye motion and visual stimulation in
      the firing of individual Purkinje cells (PCs) and mossy fibers. During tracking
      of sinusoidal target motion along different axes in the frontoparallel plane, PCs
      fell into two classes based on the axis that caused the largest modulation of
      simple-spike firing rate. For "horizontal" PCs, the response was maximal during
      horizontal eye movements, with increases in firing rate during pursuit toward the
      side of recording (ipsiversive). For "vertical" PCs, the response was maximal
      during eye movement along an axis just off pure vertical, with increases in
      firing rate during pursuit directed downward and slightly contraversive. During
      pursuit of target motion at constant velocity, PCs again fell into horizontal and
      vertical classes that matched the results from sinusoidal tracking. In addition,
      the directional tuning of the sustained "eye velocity" and transient "visual"
      components of the neural responses obtained during constant velocity tracking
      were very similar. PCs displayed very broad tuning approximating a cosine tuning
      curve; the mean half-maximum bandwidth of their tuning curves was 170-180
      degrees. Other cerebellar elements, related purely to eye movement and presumed
      to be mossy fibers, exhibited tuning approximately 40 degrees narrower than PCs
      and had best directions that clustered around the four cardinal directions. Our
      data indicate that the motion signals encoded by PCs in the monkey floccular lobe
      are segregated into channels that are consistent with a coordinate system defined
      by the vestibular apparatus and eye muscles. The differences between the tuning
      properties exhibited by PCs compared with mossy fibers indicate that a spatial
      transformation occurs within the floccular lobe.

PMID- 8738380
TI  - Ocular exploration of space as a function of neck proprioceptive and vestibular
      input--observations in normal subjects and patients with spatial neglect after
      parietal lesions.
AB  - We recently argued that the specific compensation of spatial neglect by
      manipulating neck proprioceptive and vestibular input is due to a central
      "correction" of the disturbed neural transformation process converting the
      afferent input coordinates from the peripheral sensory organs into a central
      representation of egocentric space. Both types of stimulation were proposed to
      induce a reorientation of the deviated or distorted egocentric spatial reference
      frame. The aim of the present study was to observe this process of reorientation
      under a condition in which no visual stimulus can attract the subject's attention
      and thus influence exploration behaviour from outside. We recorded eye movements
      of normal subjects and of three patients with spatial neglect after right
      parietal lesions while searching for a non-existent target in complete darkness.
      It was assumed that the area of the outer space that subjects spontaneously
      explore under this condition is a direct function of the subject's representation
      of egocentric space. Ocular space exploration was biased and confined almost
      entirely to the right side of the midsagittal plane in patients with neglect.
      This spatial distribution of exploratory eye movements changed remarkably with
      left-sided neck muscle vibration as well as with left-sided vestibular
      stimulation using ice water calorics. The spatial area of exploration was
      significantly enlarged to the contralesional side and the exploration maximum
      shifted in the same direction. Whereas with both types of stimulation space
      exploration of patients with neglect was similar to that of normal subjects when
      not being stimulated, neck proprioceptive and vestibular stimulation in normal
      subjects induced a quasi neglect-like exploration pattern, i.e. a bias to one
      side of the objective midsagittal plane. If ocular space exploration was,
      however, related to the subjectively perceived position of the midsagittal plane
      in space, eye movements were symmetrically distributed and carried out to both
      sides of subjective "straight ahead" in all experimental conditions, in normal
      subjects as well as in patients with neglect. The present results support the
      above hypothesis and indicate that neck proprioceptive as well as vestibular
      input directly contribute to the computation of the subject's central
      representation of egocentric space used for localizing body orientation and for
      guiding motor behaviour in space.

PMID- 8738379
TI  - Bilateral interactions in saccade programming. A saccade-latency study.
AB  - Subjects were required to make a saccade to a target appearing randomly 4 degree
      to the left or right of the current fixation position (1280 trials per
      experiment). Location cues were used to direct visual attention and start saccade
      preparation to one of the two locations before target onset. When the cue
      indicated the target location (valid trials), the generation of express saccades
      (visually guided saccades with latencies around 100 ms) was strongly facilitated.
      When the opposite location was cued (invalid trials), express saccades were
      abolished and replaced by a population of mainly fast-regular saccades (latencies
      around 150 ms). This was found with a peripheral cue independently of whether the
      fixation point was removed before target onset (gap condition; experiment 1) or
      remained on throughout the trial (overlap condition; experiment 2). The same
      pattern also was observed with a central cue that did not involve any visual
      stimulation at a peripheral location (experiment 3). In the case where the
      primary saccade was executed in response to the cue and the target appeared at
      the opposite location, continuous amplitude transition functions were observed:
      starting at about 60-70 ms from target onset onward, the amplitude of the cue
      elicited saccades continuously decreased from 4 degree to values below 1 degree.
      The results are explained by a fixation-gating model, according to which the
      antagonism between fixation and saccade activity gives rise to multimodal
      distributions of saccade latencies. It is argued that allocation of visual
      attention and saccade preparation to one location entails a successive
      disengagement of the fixation system controlling saccade preparation within the
      hemifield to which the saccade is prepared and a partial engagement of the
      opposite fixation system.

PMID- 8738381
TI  - Visually guided stepping under conditions of step cycle-related denial of visual
      information.
AB  - We recently reported that subjects performing a task that requires visual
      guidance of each step onto irregularly placed "stepping stones" usually fixate
      the next target of footfall just before they lift the foot to be repositioned,
      i.e. towards the end of that limb's stance phase. When negotiating the same
      walkway without ambient lighting, and with each stone's location indicated by a
      central light spot (LED), stepping and eye movements were unchanged. Under
      conditions of intermittent visual denial, in which all LEDs (the only visual
      cues) were temporarily extinguished at irregular intervals, temporal changes in
      the normal stepping pattern were sometimes observed, but stepping was not always
      affected. The primary effect of visual denial was on the leg that was in stance
      (foot in place on a stepping stone) at the moment of LED extinction, rather than
      on the leg that was in swing, and was an increase in stance duration, suggesting
      an effect on planning during this stance of the next swing towards the next
      target rather than on execution of the ongoing swing of the other leg. Subjects
      rarely failed to step onto the targets. Prolongations of stance under visual
      denial lasting 400 or 500 ms were less than 200 ms, much less than the duration
      of denial; subjects did not simply wait for the footfall target to reappear.
      There was no effect for denial lasting 300 ms; subjects performed as well as with
      a constantly visible target. Under 400 and 500 ms denial, there was no effect
      when the targets disappeared in the first 100 ms of stance (of the foot to be
      repositioned); stance durations were indistinguishable from control. This
      suggests that there is no crucial visuomotor processing by the control system(s)
      for eye and limb guidance until the target reappeared near the usual end of
      stance, when feedforward planning of the next saccade and/or swing to a target
      reaches a crucial stage, and is affected by intrusion of the period of visual
      denial. With longer (800 ms) denial there was an effect regardless of when in
      stance it began. A smaller effect of 800 ms denial sometimes visible in swing
      duration is attributable to interlimb coordination. Accurate saccades, followed
      by accurate steps, to the next target are almost always made, even when the
      target is invisible. Our results demonstrate that uninterrupted on-line visual
      information is not necessary for accurate stepping even when (as here) each step
      requires visual guidance. Also, since stance prolongations did not always result,
      and they were always much shorter than the periods of denial, we conclude that
      the visuomotor control mechanism(s) are robust in the face of substantial denial
      of all visual information including normally preferred inputs (foveal or
      peripheral images) at the normally preferred times. The fact that a saccade is
      still made to an invisible target location implies that this is useful in itself,
      since it does not result in a visible foveal image. We propose that skilled,
      visually guided stepping onto irregularly placed targets is executed under
      predominantly feedforward visuomotor control mechanisms, and suggest that the
      ability to function effectively in this way is dependent upon the integrity of
      the lateral cerebellum.

PMID- 8738382
TI  - Evidence for excitation of the human lower limb motoneurones by group II muscle
      afferents.
AB  - The possibility was investigated that stimulation of high-threshold afferents in
      the common peroneal nerve (CPN) evokes excitation of quadriceps (Q) motoneurones
      in humans. Effects of conditioning stimuli at motor threshold (1 x MT) and at
      higher intensities were compared on both the Q H-reflex and the post-stimulus
      time histogram (PSTH) of individual motor units. At 1 x MT, CPN stimulation
      evokes a facilitation, which has been shown to be caused by an interneuronally
      mediated group I excitation. Increasing the CPN stimulus intensity above 2 x MT
      caused this early excitation to increase and a later facilitation to appear both
      in the H-reflex and in the PSTH of single units. The later excitation had its
      threshold between 2 and 3 x MT, and it appeared 4-8 ms after the group I-induced
      excitation. The higher threshold and the longer latency suggest that this
      excitation is evoked by afferents with a smaller diameter than group I afferents,
      and group II afferents meet this criterion.

PMID- 8738383
TI  - Control of locomotion in the marine mollusc Clione limacina. XI. Effects of
      serotonin.
AB  - The locomotor activity in the marine mollusc Clione limacina has been found to be
      strongly excited by serotonergic mechanisms. In the present study putative
      serotonergic cerebropedal neurons were recorded simultaneously with pedal
      locomotor motoneurons and interneurons. Stimulation of serotonergic neurons
      produced acceleration of the locomotor rhythm and strengthening of motoneuron
      discharges. These effects were accompanied by depolarization of motoneurons,
      while depolarization of the generator interneurons was considerably lower (if it
      occurred at all). Effects of serotonin application on isolated locomotor and non
      locomotor pedal neurons were studied. Serotonin (5 x 10(-7) to 1 x 10(-6) M)
      affected most pedal neurons. All locomotor neurons were excited by serotonin.
      This suggests that serotonergic command neurons exert direct influence on
      locomotor neurons. Effects of serotonin on nonlocomotor neurons were diverse,
      most neurons being inhibited by serotonin. Some effects of serotonin on locomotor
      neurons could not be reproduced by neuron depolarization. This suggests that,
      along with depolarization, serotonin modulates voltage-sensitive membrane
      properties of the neurons. As a result, serotonin promotes the endogenous
      rhythmical activity in neurons of the C. limacina locomotor central pattern
      generator.

PMID- 8738384
TI  - The effect of prior back surgery on surgical outcome in patients operated on for
      lumbar spinal stenosis. A matched-pair study.
AB  - It has been widely observed that the outcome after repeat lumbar surgery is
      rarely comparable to that of primary surgery. In particular, the results of
      repeat surgery for lumbar spinal stenosis (LSS) have not been favourable. We used
      a matched-pair format in an attempt to decrease the confounding factors so as to
      determine as exactly as possible the effect of prior back surgery on the LSS
      patients' surgical outcome. The matching criteria were sex, age, myelographic
      findings, major symptom, and duration of symptoms. From one group of 251 patients
      without prior back surgery (SO patients) and another of fifty-three patients with
      one preceding back operation (RS patients), forty-one similar matched patients
      pairs (one SO and one RS-patient) were formed. There were 8 female and 33 male
      pairs. The mean age of the SO patients was 51.6 and of the RS patient 51.4 years,
      and the mean follow-up time was 4.6 and 4.4 years. The assessment of outcome was
      based on a subjective disability questionnaire. The SO patients fared
      significantly better than the RS patients (32.1 versus 41.3, P = 0.026). A short
      time interval between operations in the RS patients had a worsening effect on
      outcome, but this trend was not significant. We concluded that one preceding back
      operation had a worsening effect on the outcome of patients operated on for LSS.
      As a whole, the results of RS patients were unfavourable. The proper time for
      achieving good surgical results in LSS patients is the initial operation.

PMID- 8738385
TI  - Results of DREZ coagulations for pain related to plexus lesions, spinal cord
      injuries and postherpetic neuralgia.
AB  - The results of 58 dorsal root entry zone (DREZ) thermocoagulation procedures in
      51 patients are reported. The postoperative analgesic effect was judged by the
      patients as being good (more than 75% pain reduction), fair (25-75% pain
      reduction) or poor (less than 25% pain reduction). Of the 14 patients who
      underwent surgery for pain due to cervical root avulsion, 10 (77%) had
      permanently good (8) or fair (2) pain relief after a mean follow up period of 76
      months, another 2 (15%) experienced recurrence to the preoperative level
      (initially 1 good, 1 fair) after more than 2 and 4 years, respectively. Twenty
      two paraplegics were operated upon, 3 of whom twice, for intractable pain. After
      a mean observation time of 54 months, continuing pain relief was reported by 12
      (55%) patients (11 good, 1 fair), and one (initially fair) had recurrent pain
      after 8 months. All 3 (early) re-operations remain successful for an average
      period of 75 months. Poor results were seen especially in cases of associated
      spinal cord cysts (5 out of 7), despite combined drainage, and in patients with
      diffuse pain distribution (5 out of 6). Continuous marked improvement for longer
      periods (mean follow up: 52 months) after DREZ lesions was reported only by 2 out
      of 10 patients with postherpetic neuralgia (12 procedures) and by 1 out of 5 with
      painful states due to radiation-induced brachial plexopathy (2), previous surgery
      (2) and malignant tumour infiltration of the brachial plexus (1). Three patients
      died postoperatively due to acute cardiac failure (2) and pulmonary embolism (1).
      Major complications, especially permanent gait disturbances were observed in 6
      patients (12%) following primary procedures and in 2 out of 7 patients after re
      operations, most of them suffering from postherpetic neuralgia. Minor
      neurological deficits were noted in 9 cases (18%). DREZ lesions revealed to be an
      effective procedure in patients with pain related to root avulsion and
      paraplegia. In contrast, it seems to be less successful for painful states due to
      other plexus lesions or postherpetic neuralgia.

PMID- 8738386
TI  - The effects of malignant glioma on the EEG and seizure thresholds: an
      experimental study.
AB  - Generalised or partial seizures are a common problem with many supratentorial
      gliomas. Their underlying pathophysiological mechanisms are poorly understood. To
      investigate this problem clinical and EEG seizure thresholds were investigated in
      experimental rodent gliomas using the epileptogenic drug pentylenetetrazole
      (PTZ). Mixed C6/A15A5 malignant gliomas were grown in adult Wistar rats after
      unilateral stereotactic implantation of a 50:50 cell mix into the caudoputaminal
      region. Eleven to 14 days later EEG (raw and spectrally analysed) was recorded
      bilaterally from the frontal and parietal regions under mixed alpha-chloralose
      and urethane anaesthesia. Baseline EEG (15 minutes), EEG during and after (30
      minutes) PTZ infusion (100 microliters/min) and the time to appearance of seizure
      manifestations after starting PTZ were recorded. Fourteen animals were studied (5
      normal, 5 with tumours, 4 sham implants) and mean BP, PaCO2, PaO2 and temperature
      were similar in the three groups. Baseline raw EEG showed predominate slow wave
      activity with lower amplitude and less spontaneous activity overlying tumours.
      Following PTZ infusion a sequence of vibrissal twitching (following a mean of
      14.5 mg/kg PTZ in control and sham animals); jaw/nasal twitches (17.5 mg/kg);
      fore and hind limb jerking (46 mg/kg); myoclonic jerking (47 mg/kg); and status
      (77.5 mg/kg) was observed. The seizure thresholds for all PTZ induced seizure
      phenomena were, except for status epilepticus, highest in the tumour bearing
      animals. The time to 70% seizure activity on the EEG was also significantly
      longer in the tumour bearing animals. Spectral analysis of the EEG, although
      showing increased alpha and theta activity after PTZ infusion, did not
      discriminate between the three experimental groups either before or after PTZ
      activation. These studies have confirmed that experimental gliomas alter baseline
      EEG and both the EEG and behavioural response to PTZ. The reasons for the raised
      seizure threshold in the glioma bearing animals and the relevance of this
      experimental paradigm to human tumour associated epilepsy are discussed.

PMID- 8738387
TI  - Surgical resection of brain metastases from lung cancer.
AB  - The role of surgical resection for brain metastases is evolving. The most common
      primary for brain metastases is lung; in the US in 1992, for example, there were
      nearly 40,000 deaths with symptomatic brain metastases from lung cancer. We
      reviewed a series of 25 consecutive patients with non small cell lung cancer
      (NSCLC) undergoing open resection of one or more symptomatic brain metastases to
      consider the role of open resection. Twenty-three of the 28 resected lesions were
      3 cm or greater in diameter; 19 were solid and nine cystic. Surgical adjuncts
      included (where indicated): stereotactic biopsy, cyst drainage, and craniotomy;
      intra-operative ultrasound; and intra-operative evoked potential mapping of the
      sensorimotor area. Six patients underwent thoracotomy for resection of the lung
      primary (in all but one case, prior to craniotomy). Except for two patients who
      had whole brain radiation therapy (WBXRT) prior to referral to Neurosurgery, all
      patients underwent WBXRT (30 to 60 Gy) postoperatively. The mean survival from
      date of craniotomy was 13.1 months, with two patients still alive at ten and
      seventeen months post-craniotomy. Survival comparisons which were significantly
      different included (1) lung surgery versus no lung surgery (25.7 months versus
      9.1 months, P < 0.001), and (2) metachronous presentation of the lung primary and
      brain metastasis versus synchronous presentation (17.6 months versus 9.5 months,
      P = 0.025). Survival comparisons which were not significantly different included
      single versus multiple metastases, complete versus incomplete resection,
      adenocarcinoma versus large or squamous or cell histology, supratentorial versus
      infratentorial location, solid versus cystic metastasis, and age < or = 60 years
      versus > 60 years. These results, when compared with the literature on brain
      metastases, suggest that aggressive resection of symptomatic metastases from lung
      cancer (even if multiple) can improve functional survival over conservative
      management, and that small, asymptomatic lesions are well-controlled by WBXRT.
      They also confirm the previous finding that surgical treatment of both the lung
      primary and the brain metastases may afford the greatest period of functional
      survival for these patients.

PMID- 8738388
TI  - Type IV collagenase activity and cavernous sinus invasion in human pituitary
      adenomas.
AB  - Pituitary adenomas are regarded generally as benign tumours, but some of them can
      invade the cavernous sinus. On the other hand, matrix metalloproteinase-9 (MMP
      9), which is a type IV collagenase, recently has been found to be expressed in
      matastases and to be related to the invasiveness of various malignant tumours
      including brain tumours. In order to investigate some characteristic features of
      pituitary adenomas which invade the cavernous sinus, we examined
      immunohistological studies for MMP-9 in seven pituitary adenomas for type IV
      collagen in a dura mater and assayed for type IV collagenase activity in seven
      adenomas using type IV collagen labelled with fluorescein isothiocyaniate (FITC).
      We found immunopositive adenoma cells for MMP-9 in all invasive adenoma and
      immunopositive spindle like cells for type IV collagen in the dura mater. All
      three invasive adenomas had high levels of type IV collagenase activity (0.57
      0.72 U/ml), but the four adenomas which did not invade the cavernous sinus had
      low levels of type IV collagenase activity (0.0-0.10 U/ml). These results suggest
      that the level of type IV collagenase activity in a pituitary adenoma may be
      related to its ability to invade the cavernous sinus.

PMID- 8738389
TI  - The role of the coagulation cascade in brain edema formation after intracerebral
      hemorrhage.
AB  - The coagulation cascade has a potential role in brain edema formation due to
      intracerebral hemorrhage. In this study blood and other solutions were injected
      stereotactically into the right basal ganglia in rats. Twenty-four hours
      following injection, brain water and ion contents were measured to determine the
      amount of brain edema. Intracerebral blood resulted in an increase in brain water
      content. The amount of brain edema surrounding the intracerebral hematoma was
      reduced by a thrombin inhibitor N alpha-(2-Naphthalenesulfonylglycyl)-4-amidino
      DL-phenylalaninep iperidide, (alpha-NAPAP) infused into the hematoma after the
      clot had been allowed to solidify. The inhibitor did not alter the actual size of
      the clot mass. An artificial clot composed of fibrinogen, thrombin, and styrene
      microspheres also produced brain edema. A fibrin clot led to edema formation even
      in the absence of mass effect provided by the microspheres. The single component
      responsible for production of brain edema in all these models was thrombin. The
      edema was formed in response to a fibrinogen-independent pathway. These results
      indicate that the coagulation cascade is involved in brain edema that develops
      adjacent to an intracerebral hematoma.

PMID- 8738390
TI  - Surgical approaches for vertebro-basilar trunk aneurysms located in the midline.
AB  - Fourteen cases of midline vertebro-basilar trunk aneurysms were operated on by
      four routes of surgical approach: middle fossa anterior transpetrosal approach
      (ATP), presigmoid transpetrosal approach (PTP), conventional lateral suboccipital
      approach (LSO) or suboccipital transcondylar approach (STC). There was no
      mortality, but the morbidity was different depending on the surgical approach. In
      basilar trunk aneurysms located higher than the internal auditory canal,
      excellent results were obtainable by ATP, especially in the case of posteriorly
      projecting aneurysms. For midline vertebral aneurysms located lower than the
      internal auditory canal, STC resulted in less surgical complications than LSO.
      Extradural resection of the jugular tubercle was necessary for aneurysms located
      on the distal vertebral artery at or close to the vertebro-basilar junction. For
      vertebro-basilar junction aneurysms located at the level of the internal auditory
      canal, hearing was preserved by STC, but not by ATP or PTP. However, choice of
      the surgical approach may depend on the direction of the aneurysm and the
      technical accessibility of the skull base. All these skull base approaches
      reduced surgical complications of retraction damage to the cranial nerves and the
      brain stem. This holds true for all aneurysms arising from the midline vertebro
      basilar trunk.

PMID- 8738391
TI  - Surgical outcome for multiple intracranial aneurysms.
AB  - The surgical outcome of 221 cases with multiple intracranial aneurysms operated
      upon during the years 1988 to 1994 were reviewed. The patients were classified
      into three groups according to the locations of the aneurysms; group 1: multiple
      aneurysms located unilaterally in the anterior circulation only (147 cases);
      group 2: multiple aneurysms located bilaterally in the anterior circulation only
      (44 cases) and group 3: multiple aneurysms located in both anterior and posterior
      circulation or in the posterior circulation alone (30 cases). In 132 cases of
      group 1 (89.8%) all aneurysms were treated in one-stage operations. Twenty-eight
      patients from group 2 (63.6%) received partial treatment, where only the ruptured
      or the symptomatic aneurysms were treated. In 12 other cases from group 2 (27.3%)
      all multiple aneurysms were treated in two-stage operations. In group 3 patients,
      one-stage operations were performed in 18 cases (60%), while 9 patients (30%)
      received partial treatment only. Of the 221 multiple aneurysm cases, 162 (73.3%)
      presented with manifestations of subarachnoid haemorrhage (SAH). The remaining 59
      multiple aneurysms cases (26.7%) presented with manifestations other than SAH
      (unruptured aneurysms). In the postoperative follow-up, of the 221 multiple
      aneurysms cases, 113 (51.1%) were free of neurological deficit (excellent), 48
      cases (21.7%) were capable of leading an independent life (good), 32 cases
      (14.5%) were not independent and needed to be assisted (fair), and 28 patients
      (12.7%) died. These results were comparable to the results of patients with
      single aneurysms operated on during the same period. Based on our results, we
      recommend that whenever possible all multiple aneurysms should be treated in one
      stage operations. In unruptured multiple aneurysm cases surgical management is
      the recommended treatment. In poor grade SAH patients or unruptured multiple
      aneurysms in old patients, two-stage operations or partial treatment of only the
      ruptured or the symptomatic aneurysms may be adopted.

PMID- 8738392
TI  - Dexamethasone and colchicine reduce inflammation and delayed oedema following
      experimental brain contusion.
AB  - The effect of anti-inflammatory treatment on monocyte/macrophage infiltration,
      major histocompatibility complex molecules (MHC) class II expression and delayed
      oedema following experimental brain contusion was studied by immunohistochemistry
      and tissue-specific gravity measurement in 44 rats. Colchicine, chloroquine and
      dexamethasone administered once daily for five days after the trauma reduced
      inflammation and oedema. The difference was statistically significant with
      colchicine and dexamethasone. The findings comprise further evidence of a
      pathogenetically important inflammation after experimental contusion. It is
      probable that anti-inflammatory agents may prevent secondary neurological damage
      due to elevated intracranial pressure and cell to cell- or cytokine-mediated
      neuronal degeneration and demyelination.

PMID- 8738393
TI  - Brain tissue pO2 in relation to cerebral perfusion pressure, TCD findings and TCD
      CO2-reactivity after severe head injury.
AB  - As a reliable continuous monitoring of cerebral blood flow and/or cerebral oxygen
      metabolism is necessary to prevent secondary ischaemic events after severe head
      injury (SHI) the authors introduced brain tissue pO2 (ptiO2) monitoring and
      compared this new parameter with TCD-findings, cerebral perfusion pressure (CPP)
      and CO2-reactivity over time on 17 patients with a SHI. PtiO2 reflects the
      balance between the oxygen offered by the cerebral blood flow and the oxygen
      consumption by the brain tissue. According to TCD-CO2-reactivity PtiO2-CO2
      reactivity was introduced. After initially (day 0) low mean values (ptiO2 7.7 +/-
      2.6 mmHg, TCD 60.5 +/- 32.0 cm/sec and CPP 64.5 +/- 16.0 mmHg/, ptiO2 increased
      together with an increase in blood flow velocity of the middle cerebral artery
      and CPP. The relative hyperaemic phase on days 3 and 4 was followed by a decrease
      of all three parameters. Although TCD-CO2-reactivity was except for day 0 (1.4 +/
      1.5%), sufficient, ptiO2-CO2-reactivity sometimes showed so-called paradox
      reactions from day 0 till day 3, meaning an increase of ptiO2 on
      hyperventilation. Thereafter ptiO2-CO2-reactivity increased, increasing the risk
      of inducing ischaemia by hyperventilation. The authors concluded that ptiO2
      monitoring might become an important tool in our treatment regime for patients
      requiring haemodynamic monitoring.

PMID- 8738395
TI  - Immunohistochemical analysis of the nm23 gene product (NDP kinase) expression in
      astrocytic neoplasms.
AB  - The expression levels of nm23-H1 have been reported to correlate with the
      metastatic potential of some tumours. We have treated a child with a rare case of
      astrocytoma with diffuse osteoblastic metastases. We therefore decided to examine
      the expression of the nm23 gene product in 24 gliomas in order to clarify the
      association of its expression with the clinical features of the disease. A
      polyclonal antibody against a GST/nm23-H1 fusion protein was raised in rabbits.
      Twenty-four specimens, including 5 recurrent gliomas and one extraneural
      metastasis, were obtained from 19 patients treated surgically between 1990 and
      1993 in our hospital. Immunohistochemical staining was performed on paraffin
      sections using an avidin-biotinyl peroxidase complex method. Of the 24 astrocytic
      neoplasms, 3 (12.5%) specimens from one patient with diffuse bony metastases
      stained intensely with nm23-H1. Two specimens obtained from glioblastoma
      multiforme patients stained weakly. The other 19 specimens were negative for nm23
      H1 expression. Little or no nm23 expression was observed in adjacent nontumourous
      cerebral tissues. The results suggest that high levels of nm23 expression might
      correlate with extraneural metastatic potential in astrocytic neoplasms.

PMID- 8738394
TI  - Arterio-jugular differences of oxygen (AVDO2) for bedside assessment of CO2
      reactivity and autoregulation in the acute phase of severe head injury.
AB  - Autoregulation and CO2-reactivity can be impaired independently of each other in
      many brain insults, the so-called 'dissociated vasoparalysis'. The theoretical
      combination of preserved CO2-reactivity and impaired or abolished autoregulation
      can have many clinical implications in the daily management of brain injured
      patients. To optimize their treatment, a bedside assessment of autoregulation and
      CO2-reactivity is desirable. When cerebral metabolic rate of oxygen is constant,
      changes in arterio-jugular differences of oxygen (AVDO2) reflect changes in CBF.
      In these situations relative changes in AVDO2 can be viewed as inverse changes in
      CBF and used as an evaluation method of CO2-reactivity and autoregulation. In 39
      consecutive severe head injury patients with a mean age of 28 +/- 17 years and a
      diffuse brain injury, cerebrovascular response to changes in pCO2 was tested in
      the acute phase after injury (18 +/- 8 hours). In 28 of those cases
      autoregulation was also assessed. A relative CBF value (1/AVDO2) was calculated
      from baseline AVDO2 and was expressed as 100%. Changes in 1/AVDO2 after inducing
      pCO2 changes give a good estimate of changes in global CBF. Two different indexes
      were calculated for CO2-reactivity: 1) absolute CO2-reactivity (CO2RABS) and 2)
      percentage reactivity (CO2R%). CO2R% was used to separate patients with
      impaired/abolished CO2-reactivity from those with preserved CO2-reactivity.
      Patients with CO2R% above 1% were considered in the intact CO2-reactivity group
      and patients in whom CO2R% was below or equal to 1% were included in the
      impaired/abolished CO2-reactivity group. Only five cases (12.8%) presented an
      impaired/abolished CO2-reactivity. AVDO2 response to induced hypertension was
      studied in a subset of 28 patients. Phenylephrine was used to increase MABP about
      25%. All AVDO2 values were corrected for changes in pCO2. Patients with changes
      in 1/AVDO2 less than or equal to 20% were included in the intact autoregulation
      group. Patients with estimated CBF changes above 20% were classified as having an
      impaired autoregulation (impaired/abolished). In 12 patients (43%) autoregulation
      was intact. In the remaining 16 patients (57%) autoregulation was imparied. Of
      the 28 cases, CO2-reactivity was impaired in only five cases. All patients with
      an impaired CO2-reactivity also had an impaired autoregulation. Monitoring
      relative changes in AVDO2 permits a reliable study of CO2-reactivity and
      autoregulation at the bedside. Introducing these variables into the day-to-day
      management should be considered in treatment protocols.

PMID- 8738396
TI  - Histological changes in the normal rat brain after gamma irradiation.
AB  - Radiation-induced changes in the parietal cortex of Wistar rats were observed at
      various time points after gamma surgery. Maximum dosages of 50, 75, and 120 Gy
      were given at the iso-center of the radiation using a 4-mm collimator.
      Conventional histochemical and immunocytochemical analyses, and computer-assisted
      videomicroscopy were utilized to examine perfusion-fixed brain tissue.
      Irradiation at a dosage of 50 Gy elicited morphological changes of astrocytes in
      the parietal cortex at 3 months. Vasodilatation became obvious at 12 months;
      fibrin deposition was observed in the dilated capillary wall. Neither leakage of
      Evans Blue from the vasculature into the tissue nor necrosis was observed across
      the 12 month observation period. Irradiation at a dosage of 75 Gy resulted in
      morphological changes of astrocytes within 1 month. Dilatation of vessels and
      capillary thickening were observed at 3 months. Evans Blue leakage and necrosis
      were observed at 4 months after 75 Gy irradiation. At this time, the walls of
      arterioles became thickened by subintimal accumulation of fibrin and hyaline
      substance; this sometimes resulted in occlusion of the lumen. Significant
      hemispheric swelling was observed at 4 months. Irradiation at a dosage of 120 Gy
      elicited changes in astrocytic morphology within 3 days. Evans Blue leakage into
      the tissue was observed by 3 weeks. Vasodilation became marked at this time point
      and rarefaction was observed in the irradiated cortex. Necrosis was observed at 4
      weeks, however, no significant swelling was observed. Taken together, these
      findings demonstrate time-dependent and dosage-dependent changes in normal
      cerebral tissue after Gamma Knife irradiation. These results provide a basis for
      gauging the impact of gamma surgery in regions of eloquent tissue. An enhanced
      understanding of the cellular responses to radiosurgery will contribute to
      developing and evaluating future applications for gamma surgery.

PMID- 8738397
TI  - Angiotensin II receptor content within the subfornical organ and organum
      vasculosum lamina terminalis increases after experimental subarachnoid
      haemorrhage in rats.
AB  - Nests of cells within the central nervous system, namely the circumventricular
      organs (CVOs) which include the subfornical organ (SFO), organum vasculosum
      lamina terminalis (OVLT), area postrema (AP) and the median eminence (ME) are
      known to contain not only receptors for angiotensin II (ANG II) but also ANG II
      itself. Though the significance of this central ANG II network in the
      pathophysiology of certain conditions like hypertension is well established,
      there appears to be a lack of knowledge as to how this system might be involved
      after subarachnoid haemorrhage (SAH). In this study, we have investigated ANG II
      receptor content change at various circumventricular organs after experimental
      subarachnoid haemorrhage in rats using a transcervical transclival model. ANG II
      receptor content was detected by in vivo autoradiography using intracisternal ANG
      II Sar 1, Ile 8 labelled with iodine (I) 125 both at 30 minutes and 48 hours
      after the SAH. Serum angiotensin converting enzyme activity was also detected
      during the time course reflecting the involvement of the peripheral angiotensin
      system and showed an early rise and a fall after two days. Immunohistochemistry
      was utilized to show the ANG II-containing cells within the circumventricular
      organs. SFO and OVLT were found to have a statistically significant increase in
      ANG II receptor content persisting over two days after the SAH. These alterations
      in the receptor content of CVOs may indicate their possible role in delayed
      ischaemic deficits seen after SAH.

PMID- 8738398
TI  - A new ventriculocisternal shunt technique in treatment of noncommunicating
      hydrocephalus: a technical note with a brief discussion of the literature.
AB  - Ventriculo-cisternostomy is an established procedure for the treatment of
      noncommunicating hydrocephalus, if the underlying pathology cannot be removed. In
      cases in which the foramina of Monro and the proximal part of the third ventricle
      are obstructed, it is not possible to make a communication between the internal
      and external CSF-spaces by perforation of the floor of the third ventricle, the
      so-called third ventriculo-cisternostomy. For such cases the authors describe a
      new method of drainage of both lateral ventricles to the interpeduncular cistern.
      This new method has been used successfully in a case with obstructive
      hydrocephalus of both lateral ventricles, caused by a pilocytic astrocytoma of
      the optic chiasma and hypothalamus with obstruction of both foramina of Monro.

PMID- 8738399
TI  - Coaxial insulated bipolar electrode for monopolar and bipolar mapping of neural
      tissue: technical note with emphasis on the principles of intra-operative
      stimulation.
AB  - To facilitate use of various stimulation modes for intra-operative monitoring
      during neurosurgical procedures, we designed and produced a variable stimulation
      system that consists of a coaxial bipolar flush-tip insulated stimulation
      electrode, and a switch box to administer monopolar or bipolar stimulation
      through the same stimulation electrode. The electrode is composed of components
      that are readily available, so that its construction can be duplicated by others
      at minimal expense. For mapping of neural tissue during surgical procedures, we
      use the monopolar stimulation mode to identify relative large areas around the
      site of stimulation which are free of motor nerve fibres. The bipolar stimulation
      mode is most useful for precise localization of motor nerve fibres and in
      distinguishing motor from non-motor fibres.

PMID- 8738400
TI  - Cauda equina paraganglioma with subsequent intracranial and intraspinal
      metastases.
AB  - A case of cauda equina paraganglioma is described; subsequent intracranial and
      intraspinal metastases occurred after partial resection and adjunctive
      radiotherapy. Cerebrospinal fluid dissemination is a rare complication of spinal
      paragangliomas. Factors predictive of this unusual biological behaviour are
      discussed.

PMID- 8738401
TI  - Primary spinal leptomeningeal gliomatosis presenting visual disturbance as the
      initial symptom: case report.
AB  - We report a case of diffuse leptomeningeal gliomatosis which spread from the
      cervical to the sacral spine. A 60-year-old man was admitted with visual
      disturbance due to papilledema. Magnetic resonance imaging revealed holocord
      leptomeningeal gliomatosis without a definite intraparenchymal lesion, and the
      patient's neurological examination was unremarkable except for papilledema.
      Intracranial hypertension secondary to spinal tumor is well known but unusual,
      and the mechanism is still unclear. In our case, an elevated protein
      concentration of cerebrospinal fluid is suggested as the cause of intracranial
      hypertension.

PMID- 8738402
TI  - Isolated perfusion of the kidney with tumor necrosis factor for localized renal
      cell carcinoma.
AB  - Patients with localized renal-cell carcinoma who are candidates for renal
      parenchymal sparing surgery are being treated with isolated renal perfusion with
      recombinant human tumor necrosis factor (TNF). Isolated organ perfusion is a
      surgical technique that allows a cancer-bearing organ or region of the body to be
      treated with high doses of chemotherapy or biologic, agents that would not be
      tolerated systemically. In patients with in-transit melanoma or unresectable
      sarcoma, treatment with hyperthermic isolated limb perfusion using TNF,
      interferon-gamma, and melphalan has resulted in response rates exceeding 90%.
      Because preclinical studies suggest that TNF may induce regression of tumors by
      causing hemorrhagic necrosis mediated by effects on tumor-related vascular
      endothelium, a vascular tumor such as renal-cell carcinoma could potentially be
      very responsive. A phase I study of escalating TNF doses delivered via isolated
      renal perfusion is currently being conducted.

PMID- 8738403
TI  - Intravesical suramin: a novel agent for the treatment of superficial transitional
      cell carcinoma of the bladder.
AB  - Patients with recurrent or high-grade superficial transitional-cell carcinoma of
      the bladder that has recurred after intravesical chemotherapy are at increased
      risk for tumor invasion and metastases. Intravesical chemotherapy is a minimally
      invasive technique that allows high doses of therapeutic agents to be delivered
      directly to the malignancy, doses that would not be tolerated systemically. In
      vitro studies demonstrate suramin's significant efficacy against transitional
      cell carcinoma cell lines at relatively low doses. Humans treated with similar
      doses delivered in a systemic fashion have experienced no bladder toxicity.
      Suramin has been shown to block the binding of epidermal growth factor (EGF) to
      its receptors, which are found in large amounts in bladder cancers. Because a
      significant association has been found between the number of EGF receptors on a
      bladder-cancer cell and its sensitivity to suramin, transitional-cell carcinoma
      could potentially be very responsive to such therapy. On the basis of these
      findings, a phase I escalating-suramin-dose study is currently being conducted.

PMID- 8738404
TI  - The significance of E-cadherin in transitional-cell carcinoma of the human
      urinary bladder.
AB  - E-cadherin is a Ca(2+)-dependent intracellular adhesion molecule in the
      epithelial tissue. The urothelium also expresses E-cadherin molecules. We
      determined E-cadherin expression in bladder carcinoma immunohistochemically and
      investigated its relationship with pathological and clinical data. The percentage
      of cases showing pattern B, less than 50% of which cancer cells expressed the
      same intensity of E-cadherin as did the normal epithelium, was higher in cases of
      high-grade or high-stage tumors as compared with those of low grade or low stage.
      Heterogeneous staining was observed in the same specimens, which suggested
      changes in the cell phenotype. Immunoblotting demonstrated no evidence of gross
      alteration of E-cadherin molecules. The decrease in E-cadherin expression was
      associated with the invasiveness of bladder carcinoma, as has been reported in
      other carcinomas.

PMID- 8738405
TI  - Human urinary bladder-carcinoma cells are non-osteoinductive.
AB  - Small pieces (ca. 2-3 x 3-5 mm) of the urinary-tract mucosa from noninvasive
      papillary transitional-cell carcinomas of the bladder (ca. urotheliale papillare,
      n = 33), invasive transitional-cell carcinomas of the bladder (ca. urotheliale
      papillare infiltrans, n = 6, papillary transitional-cell carcinomas of the
      bladder with squamous metaplasia (ca. urotheliale papillare cum metaplasia
      planoepitheliale, n = 4), transitional-cell carcinomas in situ (ca. urotheliale
      in situ, n = 2), and squamous-cell carcinomas of the bladder (ca.
      planoepitheliale, n = 2) were grafted intramuscularly into cortisone
      immunosuppressed mice to test the ability of transformed transitional epithelium
      to induce heterotopic osteogenesis. Altogether, 156 implants from 47 cases of
      urinary bladder carcinoma were performed. Histological examination of implants,
      excised 10-17 days later, revealed relatively good survival of the grafted
      epithelium, which had proliferated and, in some cases, formed cysts and islands
      but failed to induce heterotopic osteogenesis in the surrounding host tissues. In
      nine implants prepared from four cases (noninvasive papillary transitional-cell
      carcinoma of the bladder and invasive papillary transitional-cell carcinoma of
      the bladder, two cases each) a small amount of cartilage and/or bone was found in
      the stroma of grafted tissue. The rarity of this phenomenon--together with the
      observation that implants of normal human urinary-tract mucosa have never induced
      the formation of cartilage/bone, whereas in a similar system, dog or guinea-pig
      grafts are osteogenic--suggests that the cartilage/bone present in the stroma of
      implanted cancers is the result of metaplasia of the stroma of the neoplasm and
      not the product of any osteoinductive potency of human urothelium.

PMID- 8738406
TI  - Increased levels of nm23 H1/nucleoside diphosphate kinase A mRNA associated with
      adenocarcinoma of the prostate.
AB  - Overexpression of the nm23H1 gene has been associated with the suppression of
      metastasis in several solid tumors. However, in colorectal carcinoma and
      neuroblastoma, increased levels of nm23 H1 nucleoside diphosphate kinase A
      (NDPKA) mRNA are associated with tumorigenesis. To determine the role of nm23
      H1/NDPKA in the prostate, normal and/or malignant tissue samples from 29
      consecutive patients were studied. Levels of nm23 H1/NDPKA mRNA and nm23 H1/NDPKA
      mRNA protein were determined in tissue from 18 and 27 patients, respectively. In
      all, 16 of the 18 tumor samples expressed increased levels of nm23 H1/NDPKA mRNA
      as compared with those measured in normal tissue. The level of nm23 H1/NDPKA mRNA
      was > 10-fold higher in a metastatic lymph node than in normal prostate tissue.
      All cancer specimens and areas of prostatic intraepithelial neoplasia showed
      immunoreactivity with the nm23 H1/NDPKA antibody; however, normal prostatic
      tissue was unreactive. These findings suggest that overexpression of the nm23
      H1/NDPKA gene occurs frequently in adeno-carcinomas of the prostate and may be an
      early event in prostate cancer tumorigenesis.

PMID- 8738407
TI  - Can prostate-specific antigen be used as a valid end point to determine the
      efficacy of chemotherapy for advanced prostate cancer?
AB  - It is current practice in many clinical trials evaluating new chemotherapy
      regimens for the treatment of advanced prostate cancer to use prostate-specific
      antigen (PSA) decline as a response criteria with the assumption that the level
      of PSA reflects the efficacy of chemotherapy. Advanced prostate cancer is
      heterogeneous; therefore, the validity of PSA decline as a measurable end point
      was studied in advanced human prostate-cancer cell lines: androgen-sensitive
      LNCaP and androgen-insensitive PC3 cells. Each cell line was grown for 4 days
      with escalating doses of Adriamycin or vinblastine. Cell counts, intracellular
      PSA concentrations, and secreted PSA levels were determined daily for 4 days.
      Untreated LNCaP cells had constant secretion of PSA per cell. In contrast, LNCaP
      cells treated with Adriamycin or vinblastine had an 80% reduction in cell numbers
      and a 3-fold increase in secreted PSA per cell by day 4. In contrast, PC3 cells
      had a different response to Adriamycin and vinblastine. Both drugs reduced cell
      numbers by 97% of control values and suppressed PSA production in the remaining
      viable cells by 4 days in culture. Thus, prostate-cancer cell production of PSA
      is variable with chemotherapy and the PSA level may not accurately reflect the
      actual tumor response to chemotherapy.

PMID- 8738408
TI  - Extracellular matrix and integrin composition of the normal bladder wall.
AB  - We performed an immunohistochemistry study of the normal human bladder so as to
      understand the interactions of extracellular matrix (ECM) components and the
      integrins of cell adhesion that accommodate the volume changes and maintain an
      impermeable barrier to reabsorption of urine in the bladder. The normal human
      urothelial cell and/or its plasma membrane contained integrins alpha 3, alpha V,
      beta 1, and beta 4 but did not contain integrin beta 3. The urothelial basement
      membrane (UBM) contained collagen type IV and laminin. Fibronectin and integrins
      alpha 3 and beta 4 were found in or near the UBM area, with types I and III
      collagen and tenascin abutting the area. The patterns of collagen, laminin,
      tenascin, vitronectin, fobronectin, and the alpha 3, alpha V, beta 1, and beta 3
      integrins in the lamina propria, vessels, nerves, and smooth-muscle layers are
      described. These findings detail the normal anatomical ECM/integrin relationship
      that provides the cellular basis for bladder-wall relationships responsible for
      its impermeable state and other functions.

PMID- 8738409
TI  - Effects of partial outlet obstruction on bladder-strip sensitivity to glucose
      deprivation: an in vitro study in the rat.
AB  - Partial outlet obstruction has been shown to result in contractile and metabolic
      dysfunctions. Specifically, there is a greater reduction in the response to field
      stimulation (FS) in comparison with the responses to bethanechol and KCl, a
      greater reduction in the tonic response to stimulation in comparison with the
      phasic response, and a reduction in oxidative metabolism of glucose accompanied
      by an increase in the glycolytic metabolism of glucose. The specific aim of the
      current study was to correlate the effects of partial outlet obstruction on the
      contractile responses of isolated strips of bladder smooth muscle to repetitive
      stimulation in the presence and absence of glucose. Adult male Sprague-Dawley
      rats were subjected to partial outlet obstruction by the surgical placement of
      silk ligatures around the urethra. After 2 weeks, each rate was anesthetized, the
      bladder was excised, and isolated strip studies were performed. These studies
      demonstrated that the maximal phasic response to FS was significantly decreased
      in the obstructed strips as compared with controls, with no difference being
      noted for responses to bethanechol or KCl; the tonic responses to all forms of
      stimulation were significantly decreased after obstruction, with the tonic
      response to FS being decreased to a greater degree than were the tonic responses
      to bethanechol and KCl; and in the absence of glucose, the tonic responses of
      control strips to all forms of stimulation were reduced to a greater degree than
      were the phasic responses. These studies demonstrate that the tonic response to
      FS is extremely sensitive to fatigue induced by repetitive stimulation.

PMID- 8738411
TI  - Polytetrafluoroethylene sling for failure in female stress incontinence surgery.
AB  - Surgery for stress urinary incontinence (SUI) in women with previous
      interventions is often difficult and yields poor results. A total of 33 women
      with recurrent SUI underwent placement of a polytetrafluoroethylene (PTFE) sling
      after a mean of 1.5 (range, 1-3) unsuccessful operations. Preoperative bladder
      instability (BI) was ruled out in all cases. The patients' mean age was 54
      (range, 34-79) years. In all, 64% had SUI and 36% had SUI and incontinence at
      rest. The Aldrige-Stoeckel technique is used with insertion of a 2 x 30 cm sling
      instead of fascia lata. Mean operating time was reduced in 40 minutes. After a
      mean follow-up period of 13 months, 72% of the patients achieved continence
      without retention (complete success). Altogether, 16 patients (48%) required self
      catheterization after discharge, with the voiding imbalance lasting for more than
      3 months in only 4 cases (12% of the total). Three patients underwent surgery for
      outlet obstruction. There were five abdominal wound infections but no vaginal
      wound infection. Two slings have since been removed (one partially), but none has
      eroded through the urethra. The PTFE sling is a reasonable option for this group
      of patients. Retention is usually self-limited, and most complications can be
      managed successfully.

PMID- 8738410
TI  - Low-angle X-ray scattering signatures of urinary calculi.
AB  - This is the first reported use of low-angle X-ray scattering for the
      investigation of urinary calculi. Low-angle X-ray scattering (LAXS) measures the
      diffraction of a broad spectrum of X-rays at a single angle and uses a
      conventional diagnostic X-ray beam, and could thus be developed for use in vivo.
      A total of 45 calculi were investigated using this technique. Calcium oxalate
      stones showed a bimodal signature with peaks of almost even photon energies.
      Signatures for the other stone types were less well-defined. The results are
      discussed in more detail below. Our preliminary results show that the technique
      is capable of distinguishing between calcium oxalate stones and other stone types
      in vitro. Further work is in progress to correlate the results of this technique
      with objective parameters of stone hardness.

PMID- 8738412
TI  - Positive ice-water test: a predictor of neurological disease?
AB  - The urinary bladder is equipped with a reflex system including cold receptors of
      the bladder wall and having reflex pathways partly separate from the normal
      micturition reflex. The ice-water test involves cooling of the bladder wall with
      ice-cold saline solution. In the neurologically intact adult the test is
      negative. A positive test indicates overt or occult neuropathy. In this report,
      examples are given of patients presenting with bladder symptoms and a positive
      test but initially lacking signs of a neurological condition. During follow-up,
      various neurogenic diseases appeared. It is suggested that a positive ice-water
      test may represent a negative prognostic urodynamic sign along with a potential
      risk for neurogenic disease to come.

PMID- 8738413
TI  - Abnormal ultrasonic pattern in contralateral testes in patients with unilateral
      testicular cancer.
AB  - Ultrasound examination and biopsy of the nonaffected testis was performed in 78
      men with a unilateral testicular cancer. Each testis was measured in three planes
      and the volume was calculated using the formula of an ellipsoid. The ultrasonic
      texture of each testis was given a score ranging from 1 to 5 as follows: 1, very
      regular; 2, slightly irregular; 3, irregular with small echogenic points; 4, very
      irregular or with coarse echogenic points; and 5, irregular with demarcated areas
      raising suspicion of tumor. Biopsies were examined for the presence of tubules
      with carcinoma in situ (CIS), germinative epithelium, Sertoli cell only, and
      obliterations; the thickness of tubular membranes and the amount of Leydig cells
      were registered. The mean ultrasonic testicular volume was 12.88 ml (range 3-24
      ml), which was smaller than that previously reported for normal men and larger
      than that previously reported for infertile men. The ultrasonic testicular volume
      was inversely correlated to the score. Score 4 was given to 46% of the testes
      (median score, 4), and the score distribution was different from that reported in
      normal men (median, 2) and in infertile men (median, 3). In all, 9 testes
      contained CIS tubules, and 8 of these were given score 4; 1 testis with CIS in
      only 5% of the tubules was given score 3. The predictive value of score 4 for the
      testis to contain CIS was 22.2%, and the predictive value of a score different
      from 4 that the testis would not contain CIS was 97.6%. We conclude that a large
      percentage of contralateral testes in men with unilateral testicular cancer have
      an abnormal echotexture and that CIS is most likely found in testes given score 4
      by ultrasound.

PMID- 8738414
TI  - Synaptobrevin is essential for secretion but not for the development of synaptic
      processes.
AB  - The formation of small synaptic vesicles represents a hallmark during
      synaptogenesis. The small synaptic vesicle protein synaptophysin is considered as
      a marker protein for synapses during neuronal development. Another small synaptic
      vesicle protein, synaptobrevin, is now well accepted to play an important role
      for the function of synapses in being a key component of exocytosis. Its role
      during synaptogenesis is not known. Tetanus toxin which exclusively proteolysis
      synaptobrevin thereby inhibiting secretion from all types of neurons was used to
      investigate consequences of inactivating synaptobrevin for the formation of small
      synaptic vesicles and synaptic contacts. In primary cultures of mouse
      hypothalamic and cerebellar neurons cultivated for 3 to 4 days, synaptobrevin
      appears earlier on small synaptic vesicles and in synaptic contacts than
      synaptophysin. Upon longer cultivation up to 12 to 14 days in vitro both proteins
      associated equally with small synaptic vesicles. Interestingly, GABA secretion
      stimulated by 50 mM potassium or 500 PM alpha-latrotoxin, did not vary during
      cultivation time. Tetanus toxin added to neuronal cultures at day 2 in vitro
      cleaved synaptobrevin and inhibited regulated GABA secretion during the whole
      cultivation time. Despite the impaired function of synaptobrevin other synaptic
      proteins such as synaptophysin, synaptotagmin, rab 3A, protein SV2, SNAP-25 and
      syntaxin were found in processes and synaptic contacts comparable to untreated
      cultures. The expression of various synaptic proteins was also followed in vivo.
      In mouse brains taken at different embryonic days, synaptobrevin, synaptotagmin,
      rab 6 and the membrane protein SNAP-25 were expressed earlier than synaptophysin
      and protein SV2. We conclude that synaptobrevin represents a marker for early
      events in synaptogenesis. Its proteolysis by tetanus toxin, however, does not
      interfere with the formation of synaptic contacts and neuronal differentiation.

PMID- 8738415
TI  - Axonal transport and targeting of the t-SNAREs SNAP-25 and syntaxin 1 in the
      peripheral nervous system.
AB  - Axonal transport and targeting of the t-SNAREs SNAP-25 and syntaxin 1 were
      investigated in the rat peripheral nervous system using a stop-flow (crush)
      technique. In crush-operated sciatic nerves, accumulations of SNAP-25 and
      syntaxin 1 immunoreactivities were detected as early as 1 h after operation,
      indicating fast axonal transport. The amounts increased on the proximal side of
      the crush with time after crushing. Distal accumulations of SNAP-25, representing
      recycling to the cell body, were less than 10% of the proximal accumulations, but
      40% for syntaxin 1, 50% for synaptobrevin II and 70% for synaptophysin.
      Immunoelectron microscopic studies demonstrated that SNAP-25 and syntaxin 1 are
      present on pleiotropic membranes within a diameter of 50 to 100 nm in axons
      proximal to a crush. Distal to the crush, labeling for syntaxin 1 and SNAP-25
      were sparse and barely detectable, respectively. In addition, the two proteins
      were found in the axolemma. In nerve terminals of the spinal cord, both proteins
      were concentrated around small synaptic vesicles (about 50 nm in diameter),
      whereas only very few gold particles were observed near the presynaptic membrane
      or the active zones.

PMID- 8738416
TI  - Colocalization of three types of intermediate filament proteins in perisinusoidal
      stellate cells: glial fibrillary acidic protein as a new cellular marker.
AB  - The presence and the colocalization of the three intermediate filament proteins,
      glial fibrillary acidic protein (GFAP) and the marker of mesenchymal liver cells,
      vimentin, were studied by an immunofluorescence double-labeling technique in
      cultures of isolated rat perisinusoidal stellate cells (PSC) and hepatocytes, in
      cocultures of isolated PSC and hepatocytes as well as in cryostat sections of rat
      liver. GFAP and vimentin immunoreactivities were localized in cultured PSC which
      were identified by the presence of the cellular marker desmin, another
      intermediate filament protein, or the stellate morphology to be seen after
      staining for one of three intermediate filament proteins. Both GFAP and vimentin
      were strongly expressed in the perinuclear region and the cell processes of
      cultured PSC. Staining for GFAP highly coincided with that for vimentin or desmin
      in cultured PSC and with that for vimentin in the liver sections. Desmin-positive
      cells were always also GFAP-positive. However, of the GFAP-positive cells only an
      estimated 50% were found desmin-positive. The coexpression of desmin and GFAP in
      the same cells appear to be unique, since apparently it has not been previously
      reported for any other cell type. Almost all of the vimentin-positive cells in
      hepatocyte culture were also expressing GFAP. Since desmin was not found in all
      of the cultured cells with PSC morphology, GFAP is suggested as a more reliable
      marker for PSC than desmin.

PMID- 8738417
TI  - Rab3D localizes to secretory granules in rat pancreatic acinar cells.
AB  - This study reports of presence of rab3D, a low M(r) GTP-binding protein, in rat
      pancreatic acinar cells and islets using a combination of Western blot analysis,
      two-dimensional sodium dodecyl sulfate polyacrylamide gel
      electrophoresis/isoelectric focusing, and light and electron microscopic
      immunocytochemistry. For these purposes, we used an affinity-purified rabbit
      polyclonal antibody generated against the exclusive amino terminus of rab3D.
      Failure to detect rab3A, B or C in pancreatic acinar cells with their respective
      antisera indicated that the rab3D immunoreactivity was not due to cross-reaction
      with rab3A, B or C. A monoclonal antiserum which recognized rab3A, B, C and D
      (clone 42.1) detected a second lower M, band in gradient gels. This protein may
      be an additional member of the rab family. Double label electron microscopic
      immunogold localizations for rab3D, and the monoclonal antibody that recognizes
      all members of the rab3 family, showed a preferential localization of rab3D to
      zymogen granules. In contrast, clone 42.1 detected both zymogen granules and
      elements of the Golgi complex. Rab3D also localized to the secretory granule
      field in pancreatic islet cells which additionally expressed rab3A. The majority
      of rab3D in acinar cells was tightly associated with membrane fractions as
      indicated by its resistance to alkaline pH extraction. It is likely associated
      with membranes via isoprenyl groups as suggested by its partitioning into the
      detergent phase in Triton X-114 extractions. In contrast, bacterially expressed
      rab3D partitioned solely into the aqueous phase in Triton X-114 extractions.
      Because of its exclusive location on zymogen granules, rab3D may play a role in
      regulated exocytosis from pancreatic acinar cells.

PMID- 8738418
TI  - Immunodetection of alpha 1-3 fucosyltransferase (FucT-V).
AB  - The fucosyltransferases constitute a family of glycosyltransferases incorporating
      fucose residues into glycoprotein or glycolipid glycans. They afford one of the
      possible termination steps of glycoconjugate biosynthesis creating the sialyl
      Lewisx or sialyl Lewisa determinant, which play an important role in cell-cell
      interaction. While cDNA, chromosomal localization and kinetic properties of a
      number of fucosyltransferases are known, immunocytochemical localization and
      trafficking studies have been delayed because of the lack of specific antibodies
      due to the pronounced homology of alpha 1, 3 fucolsyltransferases III, V and VI.
      Here we report development and characterization of monospecific polyclonal
      antibodies to alpha 1-3 fucosyltransferase V (FucT-V) and their application for
      immunodetection in transfected cells. Antisera against FucT-V were raised in two
      different ways: first by producing a fusion protein beta-galactosidase-FucT-V in
      Escherichia coli, and by synthesizing a peptide stretch specific for FucT-V.
      Polyclonal antisera were raised against each of both antigens and characterized
      by enzyme-linked immunosorbent assay, neutralization of activity, immunoblotting,
      immunofluorescence and immunoprecipitation of metabolically labeled COS cells,
      transiently transfected with cDNA encoding FucT-V. Both antibodies recognized
      only FucT-V. No cross-reactivity to FucT-III or FucT-VI was observed. FucT-V was
      localized mainly to the Golgi apparatus by colocalization with beta 1, 4
      galactosyltransferase, and to the cell surface of COS, CHO and HeLa cells.
      Expression of FucT-V in COS cells revealed three enzyme forms of 58, 53 and 50
      kDa, respectively. These size differences arose by post-translational
      modifications, as shown by pulse-chase experiments. Our results indicate that
      alpha 1-3 fucosyltransferase is a Golgi-associated enzyme and suggest its
      possible occurrence on the cell surface.

PMID- 8738419
TI  - Functional characterization of the hepatic sodium-dependent taurocholate
      transporter stably transfected into an immortalized liver-derived cell line and
      V79 fibroblasts.
AB  - Bile acids are taken up into liver parenchymal cells by active, carrier-mediated
      transport. This transport is lost during cell transformation in permanent growing
      liver tumor cell lines. In order to establish bile acid uptake in a permanent
      mammalian cell culture system, we transfected the cDNA from the cloned rat liver
      Na(+)-taurocholate cotransporting polypeptide (Ntcp) in Chinese hamster lung
      fibroblasts (V79 cells) and in a "hepatocyte-like" cell line HPCT-1F3 with three
      different gene transfer methods (calcium phosphate precipitation, lipofection,
      electroporation). A stable integration of the cDNA in both cell genomes was
      observed. However, in V79 fibroblasts, a permanent functional expression of
      taurocholate transport was not achieved. The sodium-dependent uptake of
      taurocholate was expressed permanently only in HPCT-1E3 cells, if the Ntcp was
      transfected by electroporation. In this cell line (HPCT-1E3-TC-6/2), substrate
      specificity, sodium- and energy dependence, as well as the kinetic parameters of
      the transfected single transporter were measured. The sodium-dependent
      taurocholate uptake was inhibited by addition of non-labeled bile acids,
      bumetanide, sulfobromophthalein and oligomycin. Pretreatment with 10 mM Na(+)
      butyrate of this cell culture for 22 h stimulated taurocholate uptake twofold.
      Neither butyrate-stimulated cells nor unstimulated cells transport glycocholate
      or cholate. Besides taurocholate a fluorescence-labeled taurocholate derivative,
      NBD-taurocholate, was taken up by the HPCT-1E3-TC cells. In conclusion, the
      specific gene transfer with the electroporation technique in combination with the
      "right" cell line, HPCT-1E3, has been successful for the permanent and functional
      expression of the Ntcp. This allowed direct monitoring of the solitary sodium
      dependent taurocholate transport system in a "liver cell-like" environment.

PMID- 8738420
TI  - Lymphocyte adhesion to endothelium derived from human lymphoid tissue.
AB  - The development of an efficient immune response depends on the capacity of
      antigen-specific lymphocytes to migrate into secondary lymphoid organs. The first
      step in the process of lymphocyte extravasation involves lymphocyte binding to
      the vascular endothelium. Although several adhesion receptors have been
      implicated in the migration of lymphocytes to inflamed tissue, their role in the
      extravasation of these cells to normal lymphoid organs is not yet clearly
      established. The involvement of adhesion molecules in lymphocyte entrance to
      secondary lymphoid organs can be better assessed in an in vitro system using
      endothelial cells in culture. Here we report on the isolation and culture of a
      homogeneous population of adherent cells of endothelial origin derived from human
      tonsils (TEC) and on adhesion studies performed with these cells. Beginning from
      primary cultures of human tonsils, we isolated a population of cells that we show
      by FACScan analysis to present the intracellular endothelial cell marker Von
      Willebrand factor and LVAP-2, a surface molecule present in venules from lymphoid
      organs. The cells are negative for FDC, IDC and macrophage markers. They express
      ICAM-1, VCAM-1 and CD40 both constitutively and in inducible forms and are
      induced by IFN-gamma to express major histocompatibility complex class II
      antigens. As opposed to endothelial cells from human umbilical cord (HUVEC), they
      do not need to be activated by cytokines to bind lymphoid cells via VLA-4. The
      mAb HP2/1 directed to the integrin VLA-4 blocks adhesion of Ramos and Daudi cells
      to tumor necrosis factor alpha (TNF-alpha)-treated HUVEC and to untreated TEC but
      not of tonsil-derived MNC. On the other hand, an anti-VCAM-1 antibody that blocks
      adhesion of Ramos and Daudi cells to TNF-alpha-treated HUVEC, does not block
      adhesion of these cells to TEC, suggesting the presence on the tonsillar
      endothelial cells of a ligand for VLA-4 different from VCAM-1. We show here that
      this ligand is not fibronectin.

PMID- 8738421
TI  - Loss of adhesion to basement membrane components but not to keratinocytes in
      proliferating melanocytes.
AB  - We studied the adhesive characteristics of melanocytes, cultured either in the
      presence of the mitogen phorbol 12-myristate 13-acetate (PMA) that keeps them in
      a proliferative state, or in the absence of PMA allowing them to differentiate.
      On proliferating melanocytes, several integrins, ICAM-1, E-cadherin, and CD44
      were expressed. In the absence of PMA, proliferation was arrested, melanin
      synthesis increased, and the morphology of the melanocytes became more spreaded.
      Under these conditions, expression of integrins alpha 3 beta 1 and alpha 5 beta 1
      decreased, whereas expression of alpha 2 beta 1, alpha 4 beta 1, and alpha 6 beta
      1 increased. No changes were observed for any of the other adhesion molecules.
      Immunoprecipitations from metabolically labeled cells confirmed the shift in
      integrin expression at the level of biosynthesis. The increased surface
      expression of alpha 2 beta 1 and alpha 6 beta 1 in the absence of PMA was
      accompanied by an induction of adhesion to basement membrane components collagen
      and laminin through these integrins. Integrin alpha 5 beta 1/alpha v beta 3
      mediated adhesion to fibronectin, CD44-mediated adhesion to hyaluronate, and E
      cadherin/beta 1-integrin-mediated adhesion to keratinocytes were not affected by
      PMA. These findings indicate that by selective modulation of the expression of
      adhesion molecules, adhesion to components of the basement membrane is reduced in
      proliferating melanocytes, whereas adhesion to keratinocytes is maintained.
      Similar events may be involved in melanocyte proliferation and migration during
      wound healing and initial steps of melanocytic tumor progression.

PMID- 8738422
TI  - Attachment of spores of the human pathogenic fungus Rhizopus oryzae to
      extracellular matrix components.
AB  - Fungi of the order Mucorales determine various infections involving principally
      the respiratory tract. In spite of their medical importance, little is known
      about their mechanisms of adherence to the host tissues. Thus we have attempted
      to define the morphological stages involved in the adherence process of Rhizopus
      oryzae which is the main causative agent of mucormycoses. The study of the
      kinetics of germination and adherence to plastic revealed that attachment
      occurred prior to germination and decreased dramatically with germ tube
      formation. This correlates with important modifications of the cell wall of the
      fungus with respect to both carbohydrate composition and distribution of anionic
      sites. Moreover, the attachment of spores to extracellular matrix components
      immobilized onto wells of polystyrene microtiter plates has been investigated.
      Spores adhered readily to immobilized laminin or type IV collagen, but not to
      fibronectin or the glycosaminoglycans. Attachment to laminin and collagen was
      dose-dependent and specific. Adhesion was not inhibited by the different
      carbohydrates tested, suggesting that a lectin was not involved in these
      interactions. Finally, immunofluorescence revealed that laminin and type IV
      collagen interacted exclusively with spores and mother cells of germ tubes. Thus,
      the recognition of laminin or collagen by spores may participate in their
      adherence to epithelial basement membranes exposed after epithelial tissue damage
      which frequently accompanies the predisposing factors for mucormycoses.

PMID- 8738423
TI  - Intracellular localization of antigens recognized by anti-vimentin monoclonal
      antibodies (mAbs): cross-reactivities of anti-vimentin mAbs with other cellular
      components.
AB  - Monoclonal antibodies were raised against immunoaffinity-purified fusion
      regulatory protein (FRP)-1 complex from membrane fraction of HeLa cells.
      Immunoblotting and immunoprecipitation studies showed all ten antibodies reacted
      with a 55 kDa band of cell lysate and purified vimentin. Interestingly, one of
      the antibodies (mAb57) cross-reacted with purified tropomyosin and myosin.
      Further analyses using vimentin chemically cleaved by 2-nitro-5-thio-cyanobenzoic
      acid, and lambda gt 11 cDNA which encoded a partial sequence of vimentin
      indicated that six mAbs recognized epitopes between amino acids 1 and 313 and the
      other four mAbs recognized epitopes in the area between residues 314 and 326.
      Indirect immunofluorescence microscopy using 3% formalin-fixed, 0.1% Triton X-100
      treated HeLa cells revealed that seven antibodies stained various intracellular
      components other than vimentin, while three antibodies stained vimentin filaments
      alone. Furthermore, flow cytometric analysis showed one of the antibodies (mAb25)
      clearly stained the surface of unfixed HeLa cells. All immunofluorescent findings
      were the same when HeLa, baby hamster kidney (BHK) and murine L229 cells were
      examined. These results indicate that we could obtain unique anti-vimentin mAbs
      which show cross-reactivities with previously undescribed cell surface and
      intracellular molecules including tropomyosin and myosin. Taken together, there
      are two possibilities that explain our findings: (1) The unknown molecules may
      have structural similarity to vimentin. (2) Our anti-vimentin mAbs can react
      specifically with structurally distinct epitopes present on both unknown
      molecules and vimentin. In either case, our cross-reactive mAbs, which recognized
      undescribed epitopes on vimentin, maybe provide useful tools for studying
      intermediate filaments and related cellular components.

PMID- 8738424
TI  - Effects of exogenous cAMP on the morphology and behavior of dissociated cells of
      the sponge Clathrina cerebrum (Porifera, Calcarea).

PMID- 8738425
TI  - Perspective: research highlights at the Duke University center for AIDS research.
      Immunoreconstitution in HIV infection: the role of the thymus.

PMID- 8738426
TI  - Long-term survivors with continuously high levels of HIV type 1.

PMID- 8738427
TI  - Cytokine regulation of HIV replication induced by dendritic cell-CD4-positive T
      cell interactions.
AB  - It has been established that human immunodeficiency virus (HIV) replication
      occurs throughout the course of disease in the lymphoid tissue. We have developed
      a model system to study the effect of cytokines and other agents on HIV
      replication using cocultures of DCs and T cells that reflect the cell-to-cell
      interactions that occur in the microenvironment of lymphoid tissue. Dendritic
      cells from peripheral blood, when pulsed with small amounts of HIV, induce
      infection in autologous, unstimulated CD4-positive T cells. Using this system,
      cytokines, anti-cytokine antibodies, and inhibitors of cellular activation were
      added to cultures and the effects on cellular proliferation and activation and
      HIV production were measured. Cytokines that increased T cell proliferation, such
      as IL-2 and IL-4, enhanced HIV replication, while the effect of IL-12 was more
      complex. HIV production was inhibited by blocking endogenously produced IL-2, as
      well as by adding IL-10, which blocks IL-2 secretion, antigen-presenting cell
      function, and T cell activation. Proinflammatory cytokines induced modest
      enhancement of viral replication in cocultures of HIV-pulsed DCs and CD4-positive
      T cells. Thus, using a model of HIV replication that more closely mimics the in
      vivo microenvironment of lymphoid tissue may allow a better analysis of the
      effect of cytokines and cytokine networks, as well as agents that modify immune
      activation on HIV replication.

PMID- 8738428
TI  - Antiviral effects of milk proteins: acylation results in polyanionic compounds
      with potent activity against human immunodeficiency virus types 1 and 2 in vitro.
AB  - A number of native and modified milk proteins from bovine or human sources were
      analyzed for their inhibitory effects on human immunodeficiency virus type 1 (HIV
      1) and HIV-2 in vitro in an MT4 cell test system. The proteins investigated were
      lactoferrin, alpha-lactalbumin, beta-lactoglobulin A, and beta-lactoglobulin B.
      By acylation of the amino function of the lysine residues in the proteins, using
      anhydrides of succinic acid or cis-aconitic acid, protein derivatives were
      obtained that all showed a strong antiviral activity against human
      immunodeficiency virus type 1 and/or 2. The in vitro IC50 values of the
      aconitylated proteins were in the concentration range of 0.3 to 3 nM.
      Succinylation or aconitylation of alpha-lactalbumin and beta-lactoglobulin A/B
      also produced strong anti-HIV-2 activity with IC50 values on the order 500 to
      3000 nM. All compounds showed virtually no cytotoxicity at the concentration
      used. Peptide-scanning studies indicated that the native lactoferrin as well as
      the charged modified proteins strongly bind to the V3 loop of the gp120 envelope
      protein, with Kd values in the same concentration range as the above-mentioned
      IC50. Therefore, shielding of this domain, resulting in inhibition of virus-cell
      fusion and entry of the virus into MT4 cells, may be the likely underlying
      mechanism of antiviral action.

PMID- 8738429
TI  - Potent inhibition of HIV type 1 infection of mononuclear phagocytes by synthetic
      peptide analogs of HIV type 1 protease substrates.
AB  - The HIV-1 genome encodes a protease that is required for viral processing of the
      precursor polyproteins Pr55gag and Pr160gag-pol. Interference with this process
      in human lymphocytes inhibits production of infectious virus. We tested the
      ability of several protease inhibitors to decrease replication of HIV-1BaL in
      human monocytes and peritoneal macrophages. The compounds tested are oligopeptide
      analogs of HIV-1 protease substrates in which the scissile dipeptide has been
      replaced by a hydroxyethylene isostere. The protease inhibitors were added only
      once, 1 hr prior to inoculation with virus. Every 3-5 days, half the medium was
      replaced with fresh medium. Inhibition of virus production was assessed by
      measuring reverse transcriptase (RT) activity in supernatant medium 14 days after
      infection. The concentration of drug required to inhibit infection by 50% (IC50)
      in monocytes ranged from 0.17 to 2.99 microM; IC50 values for peritoneal
      macrophages ranged from 0.21 to 1.9 microM. The IC50 values for these compounds
      were 1.1- to 10-fold higher when tested in monocytes compared to their inhibitory
      effect in lymphocytes, although still potently effective in the dosage range that
      appeared nontoxic to cells. Cell toxicity was seen only at concentrations greater
      than 10 microM, and varied among the drugs tested. Immunoblot analysis of two of
      the drugs (SB205700 and SB108922) confirmed inhibition of polyprotein processing.
      In control cells, 22% of viral protein pr55 was processed to p24 by 24 hr, and
      51% was processed by 48 hr. In cells treated with the protease inhibitors (2
      microM), Pr55 processing was inhibited 77% at 24 hr and 89% at 48 hr. Thus, these
      synthetic peptide analogs potently inhibit productive infection of mononuclear
      phagocytes by HIV-1. Drugs of this class may be useful for the treatment of HIV-1
      infection in humans.

PMID- 8738430
TI  - Generation of lymphocyte cell lines coexpressing CD4 and wild-type or mutant HIV
      type 1 glycoproteins: implications for HIV type 1 Env-induced cell lysis.
AB  - To gain more insight into the processes leading to HIV-1 Env-induced cell death,
      we aim to coexpress stably wild-type and relevant mutant variants of both HIV-1
      Env and human CD4 in lymphocyte cell lines. Here we report on the generation and
      characterization of several cell lines inducibly or constitutively expressing
      wild-type or cleavage-defective HIV-1 glycoproteins and human CD4 either singly
      or in combination. Coexpression of CD4 and wild-type Env led to the formation of
      multinucleated syncytia, to growth arrest and cell death, effects that all could
      be prevented by cultivation in the presence of monoclonal antibodies that inhibit
      cell surface membrane fusion. Cell lines coexpressing CD4 and mutated,
      noncleavable Env, detectable at the cell surface and still retaining CD4-binding
      capacity, were not retarded in their growth and cytolysis did not occur. These
      results indicate that cell lysis requires cell surface interaction of CD4 and
      gp120/41 and cleavage of gp160 to gp120 and gp41.

PMID- 8738431
TI  - Mutational analysis of two zinc finger motifs in HIV type 1 nucleocapsid
      proteins: effects on proteolytic processing of Gag precursors and particle
      formation.
AB  - To clarify the physiological function of two zinc finger motifs in the
      nucleocapsid (NC) domain of the Gag protein of human immunodeficiency virus type
      1 (HIV-1), we changed cysteine to serine in either of the two motifs or both by
      site-directed mutagenesis. Viral infectivity was lost by any of the mutations,
      but their effects appeared differently in the respective mutants. Northern blot
      analysis showed that the first finger mutant was far less efficient
      (approximately 10% of the wild type) in genomic RNA encapsidation and that the
      dual mutant of both fingers completely failed to encapsidate the RNA. In
      contrast, the second finger mutant retained its ability for RNA encapsidation
      with an efficiency similar to that of the wild type. Immunoblot analysis of the
      lysates of CD4-positive M8166 cells transfected with the mutant proviral DNAs
      showed that the processing of Gag precursors was delayed in two mutant viruses
      having alterations in the first finger sequence, whereas the processing of the
      second finger mutant appeared to be normal. On the other hand, immunoblot
      analysis of the virus particles showed that the second finger mutant particles
      contained some proteins that were thought to be degradation products of p24CA.
      Electron microscopic observation showed that all particles of these mutant
      viruses were morphologically alike except that they had a slightly larger
      diameter than that of the wild type. These results indicate that these finger
      motifs of HIV-1 NC protein do not function equivalently. Namely, the first finger
      is primarily responsible for RNA encapsidation and the second is required for
      stabilization of virus particles.

PMID- 8738432
TI  - Genetic variability and function of the long terminal repeat from syncytium
      inducing and non-syncytium-inducing human immunodeficiency virus type 1.
AB  - We analyzed sequence variability and function of the long terminal repeat (LTR)
      from syncytium-inducing (SI) and non-syncytium-inducing (NSI) HIV-1. Twenty LTR
      DNA clones were obtained by polymerase chain reaction amplification and molecular
      cloning from short-term cultures of SI and NSI viruses from an AIDS patient and
      two asymptomatic individuals, respectively. All the LTR clones tested contained
      multiple nucleotide changes (mostly G-to-A transitions), compared to the subtype
      B consensus sequence, which were clustered within the negative regulatory
      element, including NF-AT, USF, and TCF-1 alpha binding sites. The core
      promoter/TAR region sequences were highly conserved. The basal and Tat-mediated
      transcriptional activities of selected LTR clones tested were 0.1 to 1 and 0.2 to
      0.5 times that of the control, respectively, regardless of the SI or NSI origin
      of the clones. Phylogenetic analysis revealed interi-solate sequence divergence
      in the LTR that was similar but not identical to previously analyzed vif
      sequences from the same samples. In particular, the inter-isolate distances from
      reference sequences differed for the LTR and vif. This raises the possibility
      that recombination occurred between corresponding LTR and vif loci of the quasi
      species present in the isolates described here.

PMID- 8738433
TI  - Expression of HIV env gene in a human T cell line for a rapid and quantifiable
      cell fusion assay.
AB  - Human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins present at the
      surface of infected cells are known to mediate fusion with CD4-positive target
      cells. In this study we have developed a novel Env-expressing cell line for
      investigating the fusion process in a biologically significant system. Cell
      surface expression of the HIV-1 env gene, isolated from the highly fusogenic
      strain SF33, was obtained in the CD4-negative T cell line A2.01. To render the
      system versatile and efficient, HIV-1 regulatory proteins Tat and Rev were
      supplied in trans. The presence of Env at the cell surface was shown by
      cytofluorometry and immunofluorescence and precursor processing of gp160 to
      gp120/gp41 was demonstrated by Western blot. The fusion capacity of A2.01-Env
      cells was assessed by coculture with CD4-positive T lymphocytes or the fusion
      indicator cell line, HeLa-CD4-LTR-beta-Gal. By coincubation with CD4-positive T
      cells such as SupT1, A2.01-Env cells were observed to mediate rapidly numerous
      well-defined syncytia in a reproducible fashion. By expressing Tat, they also had
      the capacity to trans-activate the LTR-linked reporter beta-Gal gene following
      fusion with HeLa-CD4-LTR-beta-Gal cells. The fusion-inhibiting anti-CD4
      monoclonal antibodies Q425 and Q428 were used to block specifically Env-mediated
      fusion with CD4-positive cells and to demonstrate application of this system to
      the search for potential fusion-blocking agents. Our system thus offers a
      biologically significant model for studying fusion events with the advantages of
      being rapid, reproducible and versatile.

PMID- 8738434
TI  - Biological phenotype of HIV type 2 isolates correlates with V3 genotype.
AB  - The biological phenotype of HIV-2 isolates can be divided into two groups,
      rapid/high and slow/low, based on the ability to infect CD4+ tumor cell lines.
      Similar differences in the biological phenotype of HIV-1 isolates are largely
      determined by the charge of two specific amino acids in the V3 loop of the
      envelope protein gp120. In this study we have sequenced the V3 loop and flanking
      regions of 14 HIV-2 isolates from Guinea-Bissau and the Ivory Coast and
      correlated the results to the biological phenotype of the isolates. The sequences
      were obtained by PCR amplification of DNA from peripheral blood mononuclear cells
      infected with the different isolates, followed by direct sequencing of the
      amplified products. Eleven other HIV-2 isolates with known V3 sequence and
      biological phenotype were also included. Thirteen of the 14 new isolates were
      classified as subtype A of HIV-2 and one as subtype B. The V3 loop of rapid/high
      HIV-2 isolates differed significantly from slow/low isolates in that it was more
      heterogeneous in sequence and had higher net charge. Mutations at two specific
      amino acid positions (313 and 314), often to positively charged amino acids, were
      also significantly associated with the rapid/high phenotype. There were no
      sequence differences between rapid/high and slow/low isolates in the regions that
      flank the V3 loop. Our findings indicate that there may be a high degree of
      similarity in the molecular features that underlie the biological phenotypes of
      HIV-1 and HIV-2 isolates.

PMID- 8738435
TI  - Genomic footprinting of HTLV type I and HIV type 1 in human T cell lines.
AB  - Genomic footprinting of integrated HTLV-I and HIV-1 confirmed many aspects of
      retroviral transcriptional regulation deduced from previous studies. However,
      many notable differences were seen. HTLV-I genomic protein-binding patterns
      corresponded more closely to elements defined by transient transfection
      expression studies than to those mapped by in vitro protein-binding studies. HIV
      1 genomic footprinting showed activation-related binding to adjacent NF-KB/SP1
      sites and a large (90 bp) region transversing the R/U5 boundary, but minimal
      protein binding to NFAT, NRE, LBP-1, and CTF/NF1 sites relative to previous in
      vitro footprinting studies.

PMID- 8738436
TI  - Differential expression of human endogenous retroviral sequences similar to mouse
      mammary tumor virus in normal peripheral blood mononuclear cells.
AB  - Mouse mammary tumor virus (MMTV) is a retrovirus that causes breast cancer in
      certain strains of mice. In a previous study we identified, by sequencing clones
      from human lymphocytes, six groups with similarities to MMTV. Using a primer pair
      derived from pol sequences conserved within types A, B, and D retroviruses and
      probes from the six human MMTV-like (HML-1 to HML-6) groups in an internally
      controlled hybridization assay we investigated the normal variation of expression
      in PBMCs. Variations occurred within all groups but was most significant within
      group HML-1, where hybridization signals differed by more than 500-fold between
      individuals. Groups HML-2 and HML-3 showed consistently stronger hybridization
      signals than groups HML-1 and HML-5, while group HML-6 resulted in weak signals
      for all individuals. Stringent hybridization of the amplified cDNA to 20
      individual HML clones also demonstrated a marked heterogeneity of expression.
      Hybridization signals from some groups and sequences were found to be correlated,
      either in a positive or negative fashion. RNA isolated from PBMCs collected from
      two donors at four different time points (in the morning and in the afternoon on
      the same day, repeated 1 week later) was also analyzed using the six hml probes.
      A small variation in hybridization signals was seen in samples collected on the
      same day, but a larger difference was observed in samples taken 1 week later. The
      correlations and the differences in the expression of HMLs between individuals
      implicate a complex transcriptional regulation system of these sequences.

PMID- 8738437
TI  - HIV type 1 subtype E in commercial sex workers and injection drug users in
      southern Vietnam.

PMID- 8738438
TI  - A sequence comparison of the HIV type 1 rev trans-activator from rapid- and slow
      progressor infected infants and children.

PMID- 8738439
TI  - What is the optimal treatment for acute crystal-induced arthritis?

PMID- 8738440
TI  - Causes of failed back surgery syndrome.

PMID- 8738441
TI  - Herve Bazin, syringomyelia and lupus.

PMID- 8738442
TI  - Antibodies to cardiolipin and beta 2 glycoprotein I in patients with polymyalgia
      rheumatica and giant cell arteritis.
AB  - IgG antibodies to cardiolipin and beta 2-glycoprotein I were looked for using an
      enzyme-linked immunosorbent assay (ELISA) in 19 patients with giant cell
      arteritis (meeting 1990 American College of Rheumatology criteria), including 16
      with concomitant polymyalgia rheumatica (meeting Bird's criteria) and in three
      patients with isolated polymyalgia rheumatica. IgG anti-cardiolipin antibodies
      were demonstrated in eight patients (36%) and IgG anti-beta 2-glycoprotein I
      antibodies in two patients (9%) including one without anti-cardiolipin
      antibodies. Titers of anti-cardiolipin antibodies ranged from 27 to 190 units of
      IgG antiphospholipid antibodies (UGPL) (mean 71 UGPL). Of the eight patients with
      anti-cardiolipin antibodies, two had giant cell arteritis without polymyalgia
      rheumatica and six had polymyalgia rheumatica with clinical (n = 2) or histologic
      (n = 4) evidence of giant cell arteritis. None of the three patients with
      polymyalgia rheumatica but no giant cell arteritis had anti-cardiolipin or anti
      beta 2 glycoprotein I antibodies. The VDRL was negative in the 14 patients who
      had this test. Tests for lupus anticoagulant were performed routinely, always
      with negative results. Among giant cell arteritis patients, those who tested
      positive for anticardiolipin antibody had significantly higher values for the
      erythrocyte sedimentation rate (p < 0.006) and for serum C-reactive protein (p <
      0.03) and fibrinogen values (p = 0.05), and a trend toward higher platelet
      counts, as compared to those who tested negative for anticardiolipin antibody.
      The mean daily prednisone dose at the time of sampling was significantly lower in
      giant cell arteritis patients with anti-cardiolipin antibodies (p < 0.05); this
      difference may account for the apparent correlation between anti-cardiolipin
      antibodies and laboratory markers for inflammation. These data, as well as
      findings from serial measurements, suggest that anti-cardiolipin antibodies are
      present early in the course of giant cell arteritis and disappear within a few
      weeks of initiation of corticosteroid therapy in a dose of more than 25 mg
      prednisone per day. In this study, only one patient without anticardiolipin
      antibodies developed a cerebrovascular accident. Positive tests for anti
      cardiolipin antibody or anti-beta 2 glycoprotein I antibody in a patient with
      polymyalgia rheumatica suggest a diagnosis of concomitant giant cell arteritis,
      which is usually symptomatic.

PMID- 8738443
TI  - Corticosteroid therapy for the treatment of acute attacks of crystal-induced
      arthritis: an effective alternative to nonsteroidal antiinflammatory drugs.
AB  - To evaluate glucocorticoids as an alternative to nonsteroidal antiinflammatory
      drugs in patients with crystal-induced arthritis, a study was conducted in 27
      patients with acute attacks of gout or chondrocalcinosis. Patients with
      contraindications to nonsteroidal antiinflammatory drug therapy were given either
      a single intramuscular injection of 7 mg betamethasone (group B, n = 10) or, if
      they were receiving anticoagulant therapy, a single intravenous injection of 125
      mg methylprednisolone (group C, n = 7). The remaining patients (group A, n = 10)
      were given diclofenac in a dosage of 150 mg per day for three days then 75 mg per
      day for three days. Efficacy was evaluated based on the self-evaluated subjective
      improvement (%) and on the severity of joint swelling on days 1, 3, and 6. Both
      parameters improved promptly in all three groups. C-reactive protein decreased
      between baseline and day 6. Few patients had relapses. Glucocorticoid therapy was
      well tolerated. Our data show that a single intramuscular or intravenous
      injection of a glucocorticoid is safe and effective in patients with crystal
      induced arthritis and risk factors for intolerance to nonsteroidal
      antiinflammatory drugs.

PMID- 8738444
TI  - Diversity of opinions on the management of gout in France. A survey of 750
      rheumatologists.
AB  - Gout is a common disease. Although effective treatments are available for gout,
      there is some disagreement as to how they should be used. To study prescription
      patterns in gout, we conducted a questionnaire survey among 2520 rheumatologists.
      Seven hundred and fifty completed questionnaires were returned over a two-month
      period. Among respondents, 35.4% worked in a private office, 21% in a hospital
      and 43.6% in both. The most widely prescribed treatments in acute gout attack
      were colchicine alone (63%), colchicine with a nonsteroidal antiinflammatory drug
      (NSAID) (31.7%) and NSAID alone (5.2%), with significant variations according to
      the type of practice. Mean duration of treatment in acute gout was 18 +/- 16.8
      days (range, 3-180 days). Mean time interval between the attack and initiation of
      therapy with a xanthine oxidase inhibitor was 21.6 +/- 17.2 days (range 0-180);
      here also, significant variations were seen according to the type of practice.
      Concomitant symptomatic therapy was prescribed in 97.3% of cases, for a mean
      duration of 54 +/- 55.4 days (range 2-365). Thirty per cent of responders never
      prescribed uricosuric agents. The estimated rate of occurrence of treatment
      induced attacks increased with the reported interval between the attack and
      initiation of urate-lowering therapy. Our data demonstrate that French
      rheumatologists have widely diverging views on how to treat gout. Whether a
      waiting period is needed between an acute attack and initiation of urate-lowering
      therapy, and how long this period should be, are unsettled issues that deserve to
      be studied.

PMID- 8738445
TI  - Insufficiency fractures of the medial femoral condyle.
AB  - We report six cases of insufficiency fractures of the medial femoral condyle
      responsible for severe mechanical pain in the medial knee compartment in the
      absence of any identifiable precipitating factor. Suggestive changes were seen on
      initial roentgenograms in only one case, whereas increased radionuclide uptake
      was a consistent finding on the bone scan. The diagnosis was established only by
      magnetic resonance imaging in five cases. All six patients were women and four
      were older than 75 years. Two patients had a history of osteoporotic fractures,
      one had laboratory test evidence of osteomalacia and one had recurrent
      insufficiency fractures mistakenly ascribed for several years to migratory
      transient osteoporosis. Bone density was subnormal in five of the six patients.
      Rest and standard analgesics consistently ensured a favorable outcome within
      three to four weeks. To our knowledge there have been no previous reports of
      stress fractures of the medial femoral condyle. These lesions may be
      underdiagnosed since they are easily mistaken for primary osteonecrosis in the
      absence of magnetic resonance imaging. Primary osteonecrosis of the femoral
      condyle shares several features with insufficiency fractures, including
      predominance in elderly women with factors responsible for mechanical stress
      (varum, obesity, trivial trauma), mechanical pain, and increased radionuclide
      uptake. Because some cases of primary osteonecrosis may be secondary to
      undiagnosed stress-related microfractures, early diagnosis and elimination of
      weight bearing are essential.

PMID- 8738446
TI  - Forceful epidural injections for the treatment of lumbosciatic pain with post
      operative lumbar spinal fibrosis.
AB  - OBJECTIVE: To evaluate the efficacy of forceful epidural corticosteroid
      injections in lumbosciatic pain ascribed to post-operative lumbar spinal
      fibrosis. METHOD: Randomized controlled study comparing forceful injections via
      the sacral hiatus of 125 mg prednisolone acetate + 40 ml saline (treatment group)
      and injections via the same route of 125 mg prednisolone acetate alone (control
      group). Results were compared after six and 18 months. The main evaluation
      criterion was a subjective assessment of overall efficacy done by the patient
      using a seven-level scale. RESULTS: After six months, the proportion of patients
      who were relieved of their sciatica was significantly higher in the forceful
      injection group (n = 29; 45%) than in the control group (n = 31; 19%) (p = 0.03).
      Success rates for low back pain were 29% and 6% in the forceful injection and
      control groups, respectively. Among secondary efficacy criteria, nerve root pain
      evaluated on a visual analog scale and by Schober's index showed significantly
      greater improvement in the forceful injection group than in the control group.
      After 18 months, results were still in favor of the forceful injection group,
      with success rates of 39% for the sciatica and 31% for the low back pain. The
      proportion of patients who returned to work was similar in the two groups.
      CONCLUSION: Although mediocre overall, the results of forceful epidural
      corticosteroid injections are better than those of simple epidural injections of
      a corticosteroid alone. Given the paucity of effective treatments for
      lumbosciatic pain apparently due to postoperative fibrosis, forceful injections
      should be given a place in the treatment of this condition.

PMID- 8738447
TI  - Femoral neuralgia due to degenerative spinal disease. A retrospective clinical
      and radio-anatomical study of one hundred cases.
AB  - We report a study of 100 patients admitted to the Grenoble Regional Teaching
      Hospital between July 1985 and February 1994 for femoral neuralgia due to
      degenerative spinal disease. A herniated disk resulting in nerve root impingement
      was found in 79 patients (83 herniated disks) and lumbar spinal stenosis in 21.
      The level of nerve root compromise was L2-L3 in eight cases, L3-L4 in 35 cases,
      and L4-L5 in 40 cases. Herniated disks were divided into several groups based on
      their location with regard to the intervertebral foramen: posterolateral
      herniations were entirely contained within the spinal canal (n = 12; 14.5%),
      whereas far lateral, or foraminal, herniations (n = 71; 85.5%) involved the
      intervertebral foramen. Twenty-nine foraminal herniations (34.9%) had a component
      located within the spinal canal (medioforaminal herniations), 33 (39.8%) were
      entirely contained within the foramen (pure foraminal herniations), and nine
      (10.8%) were located lateral to the foramen (lateroforaminal herniations). As
      compared with posterolateral herniations, foraminal herniations were associated
      with shorter symptom duration at admission (p < 0.05), a greater likelihood of
      nocturnal exacerbation of pain (p < 0.001) and of a positive femoral stretch test
      (p < 0.01), and failure of the pain to worsen during Valsalva maneuvers (p <
      0.01).

PMID- 8738448
TI  - An update on orthotic devices for the lumbar spine based on a review of the
      literature.
AB  - Orthoses are often used to treat lumbar spine disorders, although their
      indications have rarely been evaluated in clinical trials. We reviewed the
      literature for data on the effects of lumbar spine orthoses. Apart from bermuda
      corsets, restriction of intervertebral mobility seems limited at the most distal
      levels (L4-L5 and L5-S1). Restriction of extreme gross spinal motions can be
      achieved and is more marked for lateral bending than for forward bending or
      extension. Stiff corsets provide greater motion restriction than flexible
      corsets, although there are wide interindividual variations. Stiff orthoses are
      associated with decreased intradiscal pressure and increased intraabdominal
      pressure. Studies of the electrical activity of trunk muscles have produced
      conflicting data as a result of marked interindividual variability. In most
      studies, use of orthotic devices did not induce muscle wasting. Although lumbar
      spine orthoses are often prescribed with the goal of inducing analgesic,
      proprioceptive and preventive effects in the workplace, whether such effects are
      actually obtained, has not been adequately evaluated. Based on our literature
      review, we have drawn a list of the main indications for orthotic devices
      according to the desired effects in various disorders of the lumbar spine.

PMID- 8738449
TI  - Simultaneous occurrence of diffuse idiopathic skeletal hyperostosis and
      ankylosing spondylitis.
AB  - To the best of our knowledge, 10 cases of Ankylosing Spondylitis (AS) and Diffuse
      Idiopathic Skeletal Hyperostosis (DISH) coexisting in the same patient have been
      reported. A new case was found in a female patient at Los Angeles Medical Center
      in 1993, which we report in this paper. We also review the literature (Medline
      1970-1994) and analyze the features of the reported cases. In order to study the
      incidence of this association in our population we have reviewed 106 cases of AS
      for radiological features of DISH. We found only one case. CONCLUSION: this is a
      rare association with an incidence of 0.94% in our patients with AS. From the
      known cases, patients showing this association present clinically mild AS in
      which radiologic findings are the basis for the diagnosis. Finally we question
      the validity of excluding the diagnosis of DISH in patients with radiological
      features of sacroiliac ankylosis.

PMID- 8738450
TI  - Abdominal aortic aneurysm. A rare cause of destructive lesions of the spine.
AB  - A case of destructive vertebral and discal lesions in a patient with chronic,
      noninfected rupture of an abdominal aortic aneurysm is reported. The main
      rheumatic manifestations of abdominal aortic aneurysms are reviewed.
      Perianeurysmal inflammation may contribute to the development of destructive
      vertebral and discal lesions.

PMID- 8738451
TI  - Autoimmune hypoglycemia occurring in tiopronin-treated rheumatoid arthritis.

PMID- 8738452
TI  - Giant cell arteritis revealed by bilateral lesions of brachial plexus.

PMID- 8738453
TI  - Intraarticular loose body in pisotriquetral osteoarthritis simulating a fracture.

PMID- 8738454
TI  - Hypothyroidism on Colchimax revealed by restless legs syndrome.

PMID- 8738455
TI  - Scanning electron-microscopic studies of the collagen architecture of the human
      sclera--normal and pathological findings.
AB  - The arrangement of the collagen fibrils of the human sclera was analyzed in the
      region of the limbus cornea, the corneoscleral trabeculum, at the zone of muscle
      insertion and at defined areas of the internal and external surface of the
      sclera. Adult eyes with no apparent pathological alterations and the sclera of a
      patient with staphyloma were examined by scanning electron microscopy. The
      investigations were performed to describe regularities in the collagen
      architecture in normal and pathologically altered eyes to understand
      pathomorphologic and pathophysiologic changes in scleral diseases.

PMID- 8738456
TI  - SEM studies of the collagen architecture of the human lamina cribrosa: normal and
      pathological findings.
AB  - The arrangement of the collagen fibrils of the lamina cribrosa was analyzed by
      using scanning electron microscopy with clinical regard to morphological
      alterations in cases of glaucoma at different stages. Adult eyes with no apparent
      pathological changes and specimens from patients with absolute glaucoma were
      studied. In the lamina cribrosa of nonpathological eyes the collagen fibrils are
      arranged circularly around the points of passage of axons and vessels. In
      specimens from glaucoma patients the characteristic circular alignment of the
      collagen fibrils around the penetrating axons is generally absent. The collagen
      fibrils are arranged in coarse bundles, showing no preferred alignment. The
      present study supports a new hypothesis for glaucoma pathogenesis.

PMID- 8738457
TI  - Evaluation of choroidal neovascularization in age-related macular degeneration
      with fluorescein and indocyanine green videoangiography.
AB  - This study is performed to evaluate the fluorescein and indocyanine green (ICG)
      characteristics of choroidal neovascularization (CNV) in age-related macular
      degeneration (ARMD). 200 eyes of 101 patients were examined with digital ICG
      videoangiography (ICGV). 190 of the 200 eyes had macular lesions of ARMD, and
      CNVs were detected in 84 (44.2%) of them. Angiographies confirmed the presence of
      well-defined CNV in 40 (47.6%) eyes and occult CNV in 44 (52.4%) eyes. On ICG
      videoangiographic examination, 6 (13.6%) of the 44 eyes with occult CNV had
      vascularized pigment epithelial detachment. 27 (61.4%) had a vascularized retinal
      pigment epithelium. Laser photocoagulation had been performed on the remaining 11
      (25%) eyes. The results of this study suggest that ICGV is a valuable technique
      in the diagnosis and evaluation of occult CNVs and may be suggested as an
      additional diagnostic tool in cases with choroidal neovascular membranes.

PMID- 8738458
TI  - HLA typing and retinitis pigmentosa.
AB  - Retinitis pigmentosa is a disease whose pathogenesis remains largely obscure. A
      lot of evidences support the hypothesis that auto-immunity is involved, but no
      HLA antigen has ever been associated with retinitis pigmentosa. Ten patients with
      autosomal recessive retinitis pigmentosa were tissue typed for class I and II HLA
      antigens. The results of the study show a significant increase in the frequency
      of the antigens Cw4, Cw6 and DR11. High values of relative risk were found also
      for some class I antigens, but the size of the group of patients with these loci
      precluded a meaningful statistical analysis.

PMID- 8738459
TI  - Contrast sensitivity with monofocal and bifocal intraocular lenses.
AB  - Bifocal intraocular lenses (BIOLs) reduce image contrast. We measured contrast
      sensitivity (CS) to evaluate the clinical significance of the loss in image
      contrast. Four groups were compared: 15 patients with a monofocal IOL, 13 with
      the True Vista BIOL, 13 with the AcuraSee BIOL, 11 with the diffractive BIOL. CS
      was measured using the Mentor B-VAT II-SG. Distance CS was slightly better in
      monofocal eyes than in all bifocal eyes, and distance CS was considerably better
      than near CS in eyes with the True Vista or the AcuraSee BIOL. With the
      diffractive BIOL, values were about the same at distance and near focus. Our
      results demonstrate that BIOLs reduce CS. thereby performing differently: both
      True Vista and AcuraSee favor distance vision, while the diffractive BIOL
      provides about the same contrast at distance and near focus.

PMID- 8738460
TI  - Grid pattern photocoagulation for diabetic macular edema--long-term visual
      results.
AB  - The authors reviewed the data of 226 eyes in 124 patients with clinically
      significant diabetic macular edema treated by grid pattern photocoagulation from
      1986 to 1994 at the Ophthalmological Clinic of Innsbruck University Hospital. On
      the basis of baseline visual acuity (VA), eyes were classified in four groups:
      group 1 = VA < 0.1; group 2 = VA 0.1-0.2; group 3 = VA > 0.2-0.5; group 4 = VA >
      0.5. The development of VA from the baseline examination until the last checkup
      in treated eyes is reported. This classification showed a better visual outcome
      after photocoagulation in eyes with a decreased VA at baseline (groups 1, 2)
      compared with eyes with a good initial VA (groups 3, 4). The difference in visual
      outcome between the second and third groups as well as between the third and
      fourth groups was statistically significant (p < or = 0.001). A correlation of
      initial VA with visual outcome after treatment was demonstrated (R = -0.558; p =
      0.0001). Clinical conclusions of these results are discussed.

PMID- 8738461
TI  - Results of surgery for paralytic exotropia due to oculomotor palsy.
AB  - In 138 cases of paralytic exotropia due to oculomotor palsy, transposition of the
      superior oblique muscle and resection of the medial rectus muscle were carried
      out. Surgery was performed with or without recession of the lateral rectus
      muscle. The long-term prognosis for 4 years or more was observed in 35 cases. We
      found that the same results could be obtained by selecting transposition of the
      superior oblique muscle in cases of complete palsy and resection of the medical
      rectus muscle in cases of incomplete palsy. There was no benefit in combining
      resection of the medial rectus muscle when performing the transposition of the
      superior oblique muscle. Regardless of which method was used, a combination with
      recession of the lateral rectus muscle greatly improved the effectiveness of the
      procedure.

PMID- 8738462
TI  - Hyperbaric oxygen treatment for macular edema in retinal vein occlusion: relation
      to severity of retinal leakage.
AB  - Twelve subjects with macular edema in retinal vein occlusion received hyperbaric
      oxygen treatment. Median visual acuity improved from 20/100 to 20/25 (p = 0.002).
      Clinically significant improvement (2 lines or more) was achieved in 10 cases
      (83%). Evaluation of the inward permeability coefficient of the blood-retinal
      barrier using vitreous fluorophotometry showed no significant alteration in the
      permeability. Studies of larger groups of vein occlusion patients are required to
      better understand and characterize the visual changes after the oxygen treatment.
      Moreover, further follow-up is required before conclusions can be reached about
      the long-term effect of this treatment.

PMID- 8738463
TI  - Influence of a single HELP application on hemorheology and retinal hemodynamics.
AB  - The heparin-induced extracorporeal low-density lipoprotein precipitation (HELP)
      eliminates selectively fibrinogen, total cholesterol, low-density lipoproteins
      (LDL) and triglycerides and improves hemorheology. We investigated the
      hemodynamic changes in 10 patients without ocular diseases performing a video
      fluorescein angiography after a single HELP procedure measuring the arm-retina
      time (ART) and the arteriovenous passage time (AVP). Laboratory parameters such
      as fibrinogen, cholesterol, LDL, triglycerides, red cell transit time, plasma and
      whole-blood viscosity were determined and retinal circulation was measured
      immediately before and after the HELP application. All of the laboratory
      parameters were lowered significantly. The ART was unaffected by the HELP
      procedure; however, there was a significant AVP reduction from 2.41 +/- 0.49 to
      1.97 +/- 0.47 (p < 0.005). These results support the hemorheological and
      hemodynamic efficiency of the HELP system in microcirculatory diseases.

PMID- 8738464
TI  - Effect of FK 506 administered topically versus intramuscularly on suppression of
      the corneal immune reaction in rats.
AB  - The immunosuppressive effect of FK 506 on penetrating keratoplasty in rats was
      evaluated following intramuscular and topical administration. Implanted corneal
      grafts were inspected weekly by clinical evaluation for 3 weeks. Cytotoxic T
      lymphocyte (CTL) activity was measured in the spleen on postoperative day 21, and
      the grafts were examined histologically. A dose of FK 506, 0.1 mg/kg given
      intramuscularly, only moderately suppressed CTL activity and the graft failed. In
      contrast, doses of either 0.024 mg/day topically or 0.3 mg/kg intramuscularly
      suppressed CTL activity and the grafts remained intact. Results suggest that FK
      506 administered topically would be effective in preventing failure of human
      corneal grafts.

PMID- 8738465
TI  - The inhibition of vitamin K3 on rabbit fibroblast proliferation in vitro.
AB  - Vitamin K3 that is commonly used to treat hemorrhagic diseases can inhibit human
      lymphatic neoplasms in vitro. This study was undertaken to investigate the
      effects of vitamin K3 on rabbit conjunctival fibroblast proliferation in cell
      culture. Vitamin K3 was added to cultured rabbit conjunctival fibroblasts.
      Remarkable inhibition was observed at a concentration of 4 mg/l. Because of its
      lower toxicity, vitamin K3 may prove to be of significant value in the treatment
      of intraocular proliferative disorders.

PMID- 8738466
TI  - Ocular complication in congenital erythropoietic porphyria.
AB  - Congenital erythropoietic porphyria (CEP), classically known as "Gunther
      disease', is an extremely rare autosomal recessively inherited disorder
      characterized by mutilating cutaneous photosensitivity and abnormal porphyrin
      heam biosynthesis in the bone marrow. So far there is no effective therapy for
      CEP. Because of severe cutaneous photosensitivity, treatment of CEP has mainly
      been focused upon the avoidance of sunlight and trauma of the skin to minimize
      skin symptoms. Recently we have encountered ocular complications, especially
      scleral involvement, in 5 CEP patients. From this point of view, we should pay
      attention not only to cutaneous symptoms but also to scleral involvement and
      ophthalmological examination is required to assess the quality of life of CEP
      patients.

PMID- 8738467
TI  - A case of uveitis associated with chronic active Epstein-Barr virus infection.
AB  - Ocular complications of chronic active Epstein-Barr virus infection (CAEBV) have
      rarely been reported. We describe a 7-year-old girl with CAEBV with associated
      uveitis. The patient was first observed to have recurrent fever and
      hepatosplenomegaly in August 1991. She presented with left facial nerve palsy in
      June 1993. Ocular examination showed right iridocyclitis. Both optic disks were
      swollen, and the retinal vessels were dilated. Antibody titers to EBV were
      markedly elevated. Treatment with topical steroids. systemic interleukin-2 and
      splenectomy dramatically relieved all her symptoms. including the ocular ones.

PMID- 8738468
TI  - A fas antigen receptor mutation allows development of toxic shock syndrome toxin
      1-induced lethal shock in V beta 8.2 T-cell receptor transgenic mice.
AB  - Recombinant toxic shock syndrome toxin-1 (rTSST-1) administered to MRL-lpr/lpr
      TCR V beta 8.2 transgenic mice at doses of 0.1 microgram/mouse resulted in 100%
      mortality. This was an unexpected finding since TSST-1 does not activate V beta
      8.2 T cells. In contrast, control mice heterozygous at the lpr locus and also for
      the transgene (MRL-lpr/+; V beta 8.2/0) survived doses of superantigen 100 times
      higher. The transgenic mice which succumbed to rTSST-1 challenge exhibited
      histopathology of the liver consistent with toxic shock (generalized inflammation
      and hepatocellular necrosis) as well as substantially elevated serum TNF-alpha,
      IL-2, and IL-6 cytokine levels. Splenic T cells derived from transgenic mice
      stimulated with rTSST-1 in vitro did not undergo detectable proliferation as
      measured in a standard mitogen assay. However, PCR amplification of cDNA prepared
      from the V beta 8.2 splenocytes revealed the presence of minor populations of
      TSST-1-reactive V beta elements (i.e. V beta 3 and V beta 15). Furthermore, an
      expansion of the V beta 3 and V beta 15 T-cell families was detected by PCR assay
      of spleen cell cultures stimulated with rTSST-1. These results suggested that the
      exquisite sensitivity of the MRL-lpr/lpr V beta 8.2 transgenic animals to rTSST-1
      was not dependent exclusively on T-cell proliferation but was augmented by the
      influence of a defective fas antigen receptor expressed in homozygous lpr mice.
      To test this hypothesis more directly, we compared the sensitivity of MRL-lpr/lpr
      mice (not carrying the V beta 8.2 transgene) to MRL-+/+ mice. The MRL-lpr/lpr fas
      antigen-defective mice were substantially more susceptible to rTSST-1 challenge.
      Mice carrying the lpr mutation on another genetic background (C57BL/6.C3H
      lpr/lpr) were also more sensitive to rTSST-1 challenge than were C57BL/6.C3H-+/+
      mice. Although induction of toxic shock is clearly associated with T-cell
      proliferation, defects in fas antigen receptor or ligand may also contribute
      substantively to superantigen-mediated lethal shock by still undefined
      mechanisms.

PMID- 8738469
TI  - In vivo function of homing receptors participating in lymphocyte recirculation:
      transfer analysis in SCID mice.
AB  - In order to examine the in vivo function of the adhesion molecules implicated in
      lymphocyte homing, blocking effects of antibodies against various adhesion
      molecules on lymphocyte migration were tested in SCID mice into which BALB/c
      donor splenocytes had been transferred. It was proved that the transferred donor
      splenocytes migrated to peripheral lymph nodes (LNs) of SCID mice. T and B
      lymphocytes were distributed in the specialized compartments as seen in the LNs
      of normal mice. Migration of lymphocytes to the local LNs was accelerated by
      stimulation with ovalbumin and complete Freund's adjuvant. This experimental
      system with accelerated migration was applied to analyze the in vivo function of
      adhesion molecules, and the following findings were obtained. Combined use of
      antibodies against lymphocyte-function-associated antigen 1 (LFA-1) and
      intercellular adhesion molecule 1 (ICAM-1) strongly inhibited the migration of T
      lymphocytes to the peripheral LNs. Antibodies against very late antigen 4 (VLA-4)
      and vascular cell adhesion molecule 1 (VCAM-1) led to diminished B lymphocyte
      migration and disturbed compartmentalization of T lymphocytes in the paracortex.
      Migration of both T and B lymphocytes to the LNs was completely inhibited by the
      antibody against L-selectin. These results indicate that L-selectin plays an
      essential role in migration of both T and B lymphocytes into peripheral LNs but
      LFA-1/ ICAM-1 and VLA-4/VCAM-1 play different roles in compartmentalization of T
      and B lymphocytes in the peripheral LNs. In contrast, these adhesion molecules
      were not involved in lymphocyte migration to the splenic white pulp, indicating
      that the mechanisms for lymphocyte homing to the white pulp are quite different
      from those to the peripheral LNs.

PMID- 8738470
TI  - Transforming growth factor-beta 1 mediates communication between human
      endometrial carcinoma cells and stromal cells.
AB  - The role of transforming growth factor-beta 1 (TGF-beta 1) in communication
      between human endometrial carcinoma (EC) cells and normal endometrial stromal
      cells (NSC) was investigated using a cell culture model. Serum-free conditioned
      medium (CMe) from EC cells (RL95-2, HEC1A) inhibited the proliferation (cells per
      colony < 50% of control; mitotic index 25-50% of control) of NSC. In contrast,
      NSC-conditioned medium (CMn) stimulated the proliferation of EC cells, but
      inhibited the growth of NSC. The proliferation of EC cells was stimulated by the
      range of dilutions of CMe which inhibited the proliferation of NSC. Using
      confocal microscopy and a monoclonal antibody, TGF-beta 1, a known product of
      differentiation in the female reproductive tract, was localized to the cytoplasm
      of NSC and EC cells. Using a protein slot-blot chemiluminescence method, secreted
      TGF-beta 1 was detected in serum-free medium conditioned by the growth of NSC and
      EC cells. TGF-beta 1 antibody-neutralized CMe or CMn stimulated the proliferation
      of both NSC and EC cells. This study suggests that endometrial carcinoma-stromal
      cell interactions involve autocrine-paracrine signaling pathways, and that TGF
      beta 1 protein is one mediator of such interactions.

PMID- 8738471
TI  - Beta 2-microglobulin and HLA-DR expression in relation to the presence of Epstein
      Barr virus in nasopharyngeal carcinomas.
AB  - We have investigated the immunohistochemical expression of beta 2-microglobulin
      and HLA-DR proteins in nasopharyngeal carcinoma (NPC) in relation to the
      expression of the Epstein-Barr virus (EBV)-encoded EBER 1-2 mRNAs and LMP-1
      protein. beta 2-Microglobulin is expressed in association with MHC-I molecules on
      most nucleated cells and HLA-DR belongs to the MHC-II molecules which are
      expressed mostly on antigen-presenting cells. Formalin-fixed paraffin-embedded
      tissue from 37 NPC cases was stained with immunohistochemistry for beta 2
      microglobulin, HLA-DR and LMP-1 proteins and by RNA in situ hybridization for
      EBER 1-2 mRNAs. beta 2-Microglobulin-positive staining was found in neoplastic
      cells in all cases. In 19/37 NPC cases the positive staining was found in most
      neoplastic cells. In the remaining 18 NPC cases more than 25% of the neoplastic
      cells showed significantly reduced or negative staining in comparison to the
      normal epithelium and infiltrating small lymphocytes. HLA-DR-positive staining
      was found in 27/37 NPC cases. EBER 1-2 transcripts were deteced in neoplastic
      cells in 13/37 NPC cases. LMP-1 expression in tumour cells was found in 4/13
      EBER1-2-positive cases. No correlation was found between the presence of EBER1-2
      transcripts or LMP-1 protein and the beta 2-microglobulin-reduced expression in
      NPC. Thus, EBV does not seem to use downregulation of MHC-I to avoid the T cell
      cytotoxic immune response in NPC. HLA-DR expression was observed in all 13 EBV
      positive cases of NPC, suggesting that EBV may participate in the induction of
      HLA-DR expression in a proportion of NPC.

PMID- 8738472
TI  - Expression of tissue factor and interleukin-1 beta in a novel rabbit model of
      disseminated intravascular coagulation induced by carrageenan and
      lipopolysaccharide.
AB  - Thrombus formation and the sequential expression of tissue factor (TF),
      interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL-1 ra) in
      several organs were examined immunohistochemically and morphometrically in a
      novel model of disseminated intravascular coagulation (DIC) developed by
      modifying the generalized Shwartzman reaction (GSR) in rabbits. The new model
      [carrageenan (CA)-lipopolysaccharide (LPS)] was induced by the administration of
      a priming dose of intraperitoneal CA, 10 mg/kg, followed 24 h later by a
      provocative dose of LPS 25 micrograms/kg, while GSR was induced by the
      intravenous injection of two doses of LPS 25 micrograms/kg. CA was detected
      predominantly within macrophages in the spleen and liver. Fibrin thrombi were
      formed as early as 1 h after the second LPS treatment in all examined organs
      reaching a peak at 3-9 h and their prevalence was higher in the CA-LPS group (p <
      0.05). The sequential expressions of TF and IL-1 beta correlated well with each
      other in both groups reaching a peak at 3-9 h with the CA-LPS group showing a
      more pronounced expression than the GSR group. Macrophages in the liver, spleen
      and lungs, and Bowman's epithelial cells expressed both proteins, while IL-1 beta
      was also expressed by endothelial and epithelial cells. IL-1 ra was expressed by
      the same cells expressing IL-1 beta, however, its expression continued to
      increase gradually over 24 h. The mortality rate was lower (p < 0.05) and
      neutrophilic sequestration less prominent in the CA-LPS group than in the GSR
      group. These findings indicate that CA efficiently replaced the priming LPS
      treatment and the consequently enhanced production of IL-1 beta may have resulted
      in the upregulation of TF expression leading to the high level of thrombi in this
      new model which may provide a tool for further studies on the role of cytokines
      in DIC.

PMID- 8738474
TI  - The role of ras GTPase activating protein in human tumorigenesis.
AB  - Abnormal signal transduction involving activated ras genes plays a major role in
      the development of a variety of tumors. Ras GTPase-activating protein (rasGAP) is
      a major contributor to the downregulation of ras by facilitating GTP hydrolysis
      of activated ras. In addition, GAP participates in the down-stream effector
      system of the ras signaling pathway. Thus, depending on the precise genetic
      alteration, its location within the gene and the effects it exerts on protein
      function, rasGAP can theoretically function as either an oncogene or as a tumor
      suppressor gene. The putative role that rasGAP plays in human tumorigenesis is
      further emphasized by two lines of indirect evidence. First, mutations within the
      C-terminal SH2 region of rasGAP in a subset of basal cell carcinomas were
      demonstrated. These are presumably activating mutations and therefore confer a
      direct oncogenic potential to rasGAP. Second, an inverse correlation between
      rasGAP protein expression and the invasive/malignant potential in human
      trophoblastic tumors was shown. Thus, in these latter tumors rasGAP functions as
      an apparent tumor suppressor gene. Employing combined laboratory techniques and
      approaches to a variety of human tumors will further define the role of rasGAP in
      tumorigenesis, provide insight into the mode of action of rasGAP and structure
      function relationships. Furthermore, it will help in establishing genotype
      phenotype correlations and potentially may lead to a pharmacological approach to
      treating choriocarcinomas.

PMID- 8738473
TI  - Chronic proliferative dermatitis in mice: neutrophil-endothelium interactions and
      the role of adhesion molecules.
AB  - The murine chronic proliferative dermatitis mutation (cpdm/cpdm) is characterized
      by epidermal hyperplasia and hyperproliferation of ventral and dorsal skin sites.
      The expression of endothelium-associated adhesion molecules was studied in
      combination with the binding capacity of various cell types on frozen sections of
      the affected skin. In correlation with the relative absence of lymphocytes in the
      cpdm/cpdm skin no lymphocyte binding could be observed, but avid adhesion of
      neutrophils was seen. Binding of neutrophils could be blocked with antibodies
      against L-selectin, LFA-1, CR3 and anti ICAM-1. No expression of vascular
      addressins or E-selectin on endothelium in the dermis was found. The cpdm/cpdm
      mutation has therefore characteristics of a psoriasis-like as well as a more
      generalized inflammatory skin condition.

PMID- 8738475
TI  - Perifusion of co-cultured hepatocytes: optimization of studies on drug metabolism
      and cytotoxicity in vitro.
AB  - The combination of co-cultivation of hepatocytes and epithelial cell lines with a
      newly developed perifusion system was used for in vitro studies on drug
      metabolism and cytotoxicity. This approach improved the viability and enhanced
      the induction of the biotransforming capacity of the hepatocytes. As demonstrated
      for the induction of 7-ethoxyresorufin O-deethylase activity by 3
      methylcholanthrene or benzanthracene, co-cultured hepatocytes in the perifusion
      system responded more sensitively to these inducers than without perifusion, most
      likely owing to stable (steady-state) concentrations of the inducers under the
      former conditions and rapidly declining concentrations under the latter
      conditions. The perifusion approach rendered it possible to determine the
      kinetics of drug metabolism during single or sequential incubations. After
      induction with 3-methylcholanthrene and phenobarbital, phase I metabolism of
      lonazolac to the monohydroxylated product in perifused co-cultures closely (87%)
      approached the values reported for the in vivo production, whereas in stationary
      co-cultures only 52% could be reached. Likewise, cytotoxic effects could be
      detected more precisely in the perifused co-cultures. If cells were pretreated
      with 0.2 mmol/L galactosamine for 3 h, perifusion with increasing concentrations
      of menadione differentially killed epithelial RL-ET-14 cells and hepatocytes at
      low and high concentrations, respectively, while in stationary co-cultures no
      differential effect was observed and only the higher concentrations were
      cytotoxic for both cells. Prevention by incubation with S-adenosylmethionine of
      menadione cytotoxicity up to a menadione concentration of 250 micromol/L was seen
      only in the perifused co-cultures, whereas in stationary cultures only a slight
      shift of the cytotoxic concentration exerting 50% cell damage to higher values
      was noted. These results demonstrate the versatile application of perifused co
      cultures for studies on drug metabolism including induction of cytochrome P450
      dependent enzymes and steady-state kinetics of biotransformation, as well as
      cytotoxic and protective effects of different drugs.

PMID- 8738476
TI  - Inhibition of gap junctional intercellular communication in heptachlor- and
      heptachlor epoxide-treated normal human breast epithelial cells.
AB  - Based on the concern of organochlorides in the environment and in human tissue,
      this study was designed to determine whether various noncytotoxic levels of
      heptachlor and heptachlor epoxide could inhibit, reversibly, gap junctional
      intercellular communication in human breast epithelial cells (HBEC). Cytotoxicity
      and gap junctional intercellular communication (GJIC) were evaluated by lactate
      dehydrogenase assay and fluorescence redistribution after photobleaching
      analysis, respectively. Both heptachlor and heptachlor epoxide were noncytotoxic
      up to 10 microg/ml. At this concentration, heptachlor and heptachlor epoxide
      inhibited GJIC of normal human breast epithelial cells after 1 h treatment.
      Within a 24 h treatment with heptachlor and heptachlor epoxide at 10 microg/ml,
      recovery of GJIC had not returned. GJIC completely recovered after a 12 h
      treatment of 1 microg/ml heptachlor epoxide, but it did not recover after a 24 h
      treatment of 1 microg/ml heptachlor. RT-PCR and Western blots were analyzed to
      determine whether the heptachlor or heptachlor epoxide might have altered the
      steady-state levels of gap junction mRNA and/or connexin protein levels or
      phosphorylation state. No significant difference in the level of connexin 43
      (Cx43) message between control and heptachlor-treated cells was observed. Western
      blot analyses showed hypophosphorylation patterns in cells treated with 10
      microg/ml heptachlor and heptachlor epoxide for 1 h with no recovery within 24 h.
      Immunostaining of Cx43 protein in normal HBEC indicated that heptachlor and
      heptachlor epoxide caused a loss of Cx43 from the cell membranes at noncytotoxic
      dose levels. Taken together, these results suggest that heptachlor and heptachlor
      epoxide can alter GJIC at the post-translational level, and that, under the
      conditions of exceeding a threshold concentration in the breast tissue containing
      'initiated' cells for a long time and not being counteracted by anti-tumor
      promoting chemicals, they could act as breast tumor promoters.

PMID- 8738477
TI  - Characterization of rat lymphocyte primary culture for the development of an in
      vitro mutagenesis assay: effect of interleukin-2 and 2-mercaptoethanol on the
      activities of intermediary metabolism enzymes and cell proliferation.
AB  - Efficient energy utilization is essential for cell growth; in an attempt to
      improve the growth conditions of the rat T-lymphocyte culture model for potential
      use in studying the mutagenic activity of carcinogens in vitro, we have
      investigated the effects of phytohemagglutinin (PHA), interleukin-2 (IL-2) and 2
      mercaptoethanol (2-ME) on the activities of intermediary metabolism enzymes and
      cell proliferation. Isolated lymphocytes were cultured in the presence and
      absence of PHA, IL-2, or 2-ME. The intermediary metabolism enzymes investigated
      were glutamate dehydrogenase, glutamate-pyruvate transaminase, malate
      dehydrogenase, isocitrate dehydrogenase, lactate dehydrogenase, pyruvate kinase,
      and fatty acid synthetase (FAS). Measurable activity of all enzymes investigated,
      except for FAS, was detected in PHA-stimulated cells cultured with IL-2 or 2-ME.
      The unstimulated lymphocytes had significantly lower enzyme activity than
      stimulated cells. The combination of all three agents showed increased enzyme
      activity. This increase in activity brought about by the combination of the three
      agents was not reproduced by either agent acting alone. In general, the increase
      in enzyme activity correlated with cell proliferation as measured by
      [3H]thymidine uptake in PHA-stimulated cultures containing IL-2 and/or 2-ME. The
      results suggest that the addition of exogenous IL-2 and 2-ME enhances metabolic
      function and may be beneficial in in vitro culture of rat lymphocytes.

PMID- 8738478
TI  - Cytoprotective and antioxidant effects of boldine on tert-butyl hydroperoxide
      induced damage to isolated hepatocytes.
AB  - Boldine, an aporphine alkaloid, was recently shown by us to exhibit potent
      antioxidant properties. We report here that boldine concentration-dependently
      inhibited the peroxidative (accumulation of thiobarbituric acid reactive
      substances) and lytic damage (trypan blue exclusion and lactate dehydrogenase
      leakage) to isolated rat hepatocytes induced by tert-butyl hydroperoxide (TBOOH).
      Boldine (200 micromol/L) fully cytoprotected and completely prevented the
      peroxidation induced by TBOOH at concentrations equal to or lower than 0.87
      mmol/L. However, at a peroxide concentration of 0.91 mmol/L, although boldine
      completely inhibited lipid peroxidation it largely failed to afford
      cytoprotection against TBOOH. TBOOH alone (0.83 mmol/L) caused an early (within
      60 s) sudden decline of reduced glutathione (by 50%) and an equivalent increase
      in the levels of oxidized glutathione. Neither of these effects was prevented by
      the simultaneous addition of a cytoprotective and antioxidant concentration of
      boldine (200 micromol/L). The delayed addition of boldine to the suspension
      (after 10 or 20 min), while effectively blocking any further increase in
      thiobarbituric acid reactive substances, totally failed to prevent the peroxide
      induced loss in cell viability. Conversely, preincubation of the hepatocytes with
      boldine for 150 min (at which time no boldine could be detected in either intra-
      or extracellular spaces) prevented lipid peroxidation and was as effective in
      protecting the cells against the damage caused by the subsequent addition of
      TBOOH as the simultaneous addition of boldine and TBOOH to hepatocytes
      preincubated for 150 min under control conditions.

PMID- 8738479
TI  - Translational suppression by Ca2+ ionophores: reversibility and roles of Ca2+
      mobilization, Ca2+ influx, and nucleotide depletion.
AB  - The divalent cation selective ionophores A23187 and ionomycin were compared for
      their effects on the Ca2+ contents, nucleotide contents, and protein synthetic
      rates of several types of cultured cells. Both ionophores reduced amino acid
      incorporation by approximately 85% at low concentrations (50-300 nmol/L) in
      cultured mammalian cells without reducing ATP or GTP contents. At these
      concentrations A23187 and ionomycin each promoted substantial Ca2+ efflux,
      whereas at higher concentrations a large influx of the cation was observed. Ca2+
      influx occurred at lower ionophore concentrations and to greater extents in C6
      glioma and P3X63Ag8 myeloma than in GH3 pituitary cells. The ATP and GTP contents
      of the cells and their ability to adhere to growth surfaces declined sharply at
      ionophore concentrations producing increased Ca2+ influx. Prominent reductions of
      nucleotide contents occurred in EGTA-containing media that were further
      accentuated by extracellular Ca2+. Ionomycin produced more Ca2+ influx and
      nucleotide decline than comparable concentrations of A23187. The inhibition of
      amino acid incorporation and mobilization of cell-associated Ca2+ by ionomycin
      were readily reversed in GH3 cells by fatty acid-free bovine serum albumin,
      whereas the effects of A23187 were only partially reversed. Amino acid
      incorporation was further suppressed by ionophore concentrations depleting
      nucleotide contents. Mitochondrial uncouplers potentiated Ca2+ accumulation in
      response to both ionophores. At cytotoxic concentrations Lubrol PX abolished
      protein synthesis but did not cause Ca2+ influx. Nucleotide depletion at high
      ionophore concentrations is proposed to result from increased plasmalemmal Ca2+
      ATPase activity and dissipation of mitochondrial proton gradients and to cause
      intracellular Ca2+ accumulation. Increased Ca2+ contents in response to Ca2+
      ionophores are proposed as an indicator of ionophore-induced cytotoxicity.

PMID- 8738480
TI  - Inducibility of ethoxyresorufin deethylase and UDP-glucuronosyltransferase
      activities in two human hepatocarcinoma cell lines KYN-2 and Mz-Hep-1.
AB  - Two human hepatoma cell lines, KYN-2 and Mz-Hep-1 were characterized in terms of
      glucuronidation capacity and inducibility of cytochrome P4501A1/1A2 and several
      UDP-glucuronosyltransferases (UGTs). Cytochrome P4501A1/1A2 activity was measured
      using 7-ethoxyresorufin and that of UGTs with 16 different substrates. The
      effects of dimethyl sulfoxide (DMSO), 3-naphthoflavone, alpha-naphthoflavone, and
      rifampicin on these drug-metabolizing enzyme activities were studied. DMSO
      treatment increased in a dose-dependent manner the ethoxyresorufin O-deethylase
      (EROD) activity in KYN-2 cells, while an opposite effect was observed in Mz-Hep-1
      cells. In KYN-2 cells, EROD was more responsive toward beta-naphthoflavone
      treatment in combination with DMSO. This activity was enhanced in Mz-Hep-1 cells
      more than 83 times by beta-naphthoflavone. The enhancement of EROD activity by
      DMSO and beta-naphthoflavone treatments of KYN-2 cells was abolished by alpha
      naphthoflavone treatment. In Mz-Hep-1, only the inducing effect of beta
      naphthoflavone was abolished by alpha-naphthoflavone treatment. Rifampicin
      treatment of KYN-2 cells reversed both the DMSO and beta-naphthoflavone effects
      on the EROD activity. Glucuronidation of steroids, bile acids, fatty acids and
      drugs was effective in KYN-2 and Mz-Hep-1 cells. Both 1-naphthol glucuronidation
      and the level of UGT1*6 protein detected by immunoblot and supporting this
      activity were lowered by DMSO treatment and increased by beta-naphthoflavone
      treatment in KYN-2 cells. In Mz-Hep-1 cells, DMSO and beta-naphthoflavone had no
      effect on 1-naphthol glucuronidation activity. DMSO, beta-naphthoflavone and
      rifampicin also affected the glucuronidation of various substrates supported by
      different UGT isoforms. These results indicate that KYN-2 and Mz-Hep-1 cells can
      be used as new in vitro models for the studies of drug metabolism and the
      regulation of the corresponding enzymes.

PMID- 8738481
TI  - Current pathological classification of pituitary adenomas.
AB  - A classification of pituitary adenomas basing on detailed structural and
      immunohistochemical studies is accepted world-wide and is mandatory for each
      pathologist. Monohormonal (densely or sparsely granulated GH cell adenomas,
      Prolactin cell adenomas, ACTH cell adenomas. FSH/LH cell adenomas, alpha-subunit
      only adenomas), bihormonal (mixed GH/Prolactin cell adenomas, mammosomatotroph
      cell adenomas, acidophil stem cell adenomas), plurihormonal
      (GH/Prolactin/Glycoprotein-positive adenomas, other Glycoprotein-positive types)
      and hormone-negative adenomas (null cell adenomas, oncocytic adenomas) have to be
      differentiated.

PMID- 8738482
TI  - Molecular biological research in pituitary adenomas from the pathologists' view.
AB  - Some recent findings related to pituitary adenoma pathology achieved by molecular
      biological methods are briefly reviewed. It is increasingly obvious that the
      application of the molecular pathology approach can provide a deeper insight into
      the causation, histogenesis, cellular derivation and differentiation as well as
      progression of pituitary adenomas and can help to understand better structure
      function correlations.

PMID- 8738483
TI  - Molecular biology of growth-hormone-secreting human pituitary tumours:
      biochemical consequences and potential clinical significance.
AB  - Molecular biological studies have revealed that 30-40% of GH-secreting human
      pituitary tumours, associated with acromegaly, harbour single-base missense
      mutations within the Gs alpha gene, termed gsp oncogenes. In addition, a large
      proportion of GH-secreting tumours inappropriately express the GH-releasing
      factor (GRF) gene. Gsp-oncogenes result in elevated adenylyl cyclase activity
      with consequent abnormally high cAMP production. In culture, GH-secreting tumours
      expressing gsp oncogenes respond more efficiently to the somatostatin analogue,
      octreotide (SMS), raising the possibility that acromegalics harbouring gsp
      positive tumours may be those who optimally benefit from SMS therapy.
      Inappropriate expression of GRF may result in abnormal presence of a positive
      autocrine feedback loop, in which secreted GRF acts on the same cells to promote
      cellular proliferation and GH secretion. Blockade of GRF mRNA translation by
      means of anti-sense oligonucleotide approaches may prove to be of value in
      inhibiting tumour function.

PMID- 8738484
TI  - Surgical results in microadenomas.
AB  - Pituitary microadenomas are small tumors whose maximal diameter is less than 1
      cm. The aim of surgical removal of microadenomas should be not only the reversal
      of hormone hypersecretion but also the preservation of normal anterior pituitary
      function. Our series includes 230 patients with a microadenoma who had their
      first operation in our department: 45 were GH-secreting, 92 were PRL-secreting,
      90 were ACTH-secreting, and 3 were TSH-secreting. Remission of disease was
      achieved in 81%, 77%, 91%, and 100% of GH-, PRL-, ACTH-, and TSH-secreting
      adenomas, respectively. There was no perioperative mortality and only 5 patients
      experienced a major complication. A total of 7 patients had diabetes insipidus
      for at least 6 months after operation. Hypopituitarism, not present in any
      patients before operation, developed in 3.5% of the cases. Our experience
      confirms that patients with microadenomas have the best chances of a successful
      operation. Since tumor size should gradually increase with time, we underscore
      the need of early diagnosis and treatment in patients with pituitary adenomas.

PMID- 8738485
TI  - Management of huge pituitary adenomas.
AB  - Management of huge pituitary adenoma (more than 5 cm in diameter) is one of the
      most important issues on the treatment of pituitary tumors. We have analyzed the
      therapeutic modality and the result of our cases. From 1967 to 1983, 50 patients
      with huge adenoma (14.1%) out of a total 354 pituitary adenomas were surgically
      treated. The operative mortality was 25% for radical transcranial (TC) approach
      (10/40), 14% (1/7) for transsphenoidal (TS) approach and 0% (0/3) for combined
      two stage operations. From long-term follow-up, excellent prognoses were observed
      in only 44% of the patients treated by radical TC operation. After 1984, we have
      employed partial removal by TS surgery at the first stage, followed by
      reoperation by TS or TC surgery with or without radiotherapy or bromocriptine in
      case by case. Seventeen huge pituitary adenomas out of a total 700 pituitary
      adenomas were operated. There was no mortality nor major complications. The two
      stage operation with initial TS surgery is recommended for the management of huge
      pituitary adenomas.

PMID- 8738486
TI  - The role of transcranial surgery in the management of pituitary adenoma.
AB  - Transcranial pituitary surgery has a small, but distinct, role in the management
      of pituitary adenomas. Properly performed, a transcranial procedure should have
      an associated morbidity and mortality not much different than that of a
      transsphenoidal operation.

PMID- 8738487
TI  - Proliferation parameters for pituitary adenomas.
AB  - In this review, the value of assessing proliferation parameters in surgically
      resected pituitary tumour tissue is analyzed. Histological examination of basal
      dura biopsies identifies invasive growth even when intraoperatively not apparent
      to the surgeon. Determination of DNA-polymerase activity, Ki-67
      immunohistochemistry and DNA-flow-cytometry shows a clear difference in the
      proliferative potential of enclosed and invasive pituitary adenomas. Among the
      various endocrinologically differentiated groups ACTH-secreting adenomas
      associated with Nelson's syndrome and thyrotropinomas were the most rapidly
      proliferating. At present, however, our results reveal that the prognosis of an
      individual patient cannot be reliably predicted on the basis of such studies.

PMID- 8738488
TI  - Protein kinase C and growth regulation of pituitary adenomas.
AB  - The present study was undertaken to explore the role of the Protein Kinase C
      (PKC) signal transduction system in growth regulation of pituitary adenomas.
      Primary tumor cultures were plated from fresh surgical tumor specimens. The PKC
      inhibitors Staurosporine and Tamoxifen were added at varying dosages to the cell
      cultures. Measurements of cell proliferation were performed by [3H]-thymidine
      uptake and the [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide]
      (MTT) assay. After a 48 h treatment period, both [3H]-thymidine uptake and
      absorbance on the MTT assay decreased in a dose-related manner in both the
      staurosporine and tamoxifen-treated cultures (IC50 of 10 nM and 30 microM
      respectively). Direct measurement of PKC activity using an in vitro assay
      revealed very high activity (range of 1465-5708 pmol/min/mg protein; within the
      range previously published for malignant glioma specimens) in 12 frozen specimens
      of pituitary adenomas (9 nonfunctional adenomas, 1 prolactinoma, 1 gonadotrophin
      secreting and 1 corticotroph-secreting adenoma). In contrast, PKC activity
      measured in normal adenohypophysis was comparatively very low. These data
      indicate that pituitary adenoma cells display high PKC activity and are sensitive
      to growth inhibition by PKC inhibitors. These data suggest a role for the PKC
      system in regulating pituitary tumor growth, which may have implications for
      future therapy of these tumors.

PMID- 8738489
TI  - MR imaging of residual tumor tissue after transsphenoidal surgery of hormone
      inactive pituitary macroadenomas: a prospective study.
AB  - 22 patients were examined by magnetic resonance (MR) imaging before and after
      transsphenoidal surgery of hormone-inactive pituitary macroadenomas to evaluate
      for tumor removal. MR imaging was performed without and with gadolinium-DTPA
      before the operation and 3 months after. In all cases a suprasellar tumor
      extension was found preoperatively, in 9 cases with an additional parasellar, in
      2 cases with an additional retrosellar extension (average diameter 2.5 cm). In 7
      cases complete tumor removal was shown by postoperative MR, but in 11 cases
      residual tumor tissue was found (4 x suprasellar, 5 x parasellar, 2 x
      retrosellar). In 4 patients postoperative MR could not clearly differentiate
      residual tumor from scar formation. Although in cases of residual tumor follow-up
      MR imaging was performed over a period of two years, residual tumor volumes did
      not appear to change. This study demonstrates that MR imaging is highly sensitive
      for evaluating residual tumor tissue after transsphenoidal surgery of hormone
      inactive macroadenomas.

PMID- 8738490
TI  - Persistent and recurrent hypercortisolism after transsphenoidal surgery for
      Cushing's disease.
AB  - After transnasal operations in Cushing's syndrome persisting hypercortisolism
      either due to negative pituitary exploration or due to subtotal tumor removal,
      and recurrence of the disease after successful surgery still are challenging. We
      report on the therapeutic failures among 310 consecutive patients who underwent
      primary transsphenoidal microsurgery for Cushing's disease. In 287 patients an
      ACTH-producing pituitary adenoma could be detected (finding rate: 92.6%). In 264
      cases remission of hypercortisolism could be attained (remission rate with
      adenoma 92.0%, for the whole series of primary operations 85.2%). In 23 patients
      no adenoma could be found despite extensive pituitary exploration (7.4%). Here,
      we will focus on the management of the 23/287 patients with persistent
      hypercortisolism after transnasal tumor operation (8.0%) and those 29 cases of
      the 264 patients with a remission who developed a recurrence of hypercortisolism
      (11.0%). In recurrent hypercortisolism we recommend transsphenoidal reoperation
      even when no tumor is visible in MRI. Seventeen of 24 reoperations in recurrent
      Cushing's disease were successful (70.8%). In persistent hypercortisolism we
      perform a reoperation during the same hospital stay. Nine of 16 early
      reoperations led to remission of hypercortisolism (56.3%). If transsphenoidal
      reoperation fails we indicate radiation therapy of different modalities depending
      on the extension and location of the tumor remnants. Bilateral adrenalectomy is
      proposed by us only if all other therapeutic measures failed.

PMID- 8738491
TI  - Surgical treatment of pituitary adenomas in elderly patients.
AB  - Partly due to increased life expectancy, more and more patients over 60 years of
      age present with neurosurgical problems. In each case you have to decide to
      operate a patient or not. Describing the management in pituitary adenomas we
      conclude that also in elderly people operative therapy via the transsphenoidal
      approach can be done with a low risk in most cases.

PMID- 8738492
TI  - Combined surgery and radiotherapy of invasive pituitary adenomas--problems of
      radiogenic encephalopathy.
AB  - The aim of the present study was to find out: can combined modality of surgery
      and local irradiation in case of invasive pituitary adenomas prevent tumour
      relapse and develop radiogenic late damage after this therapy. Thirty-three
      patients suffered from primary hypophysomas and twenty-three patients had
      pituitary tumour recurrences. In all cases combined therapy was performed. The
      long term results of 56 patients showed a recurrence rate of 5.4% (3 cases). The
      median follow-up time was 152 months, ranging from 101 to 197 months. Clinical
      and neuroradiological signs of radiogenic encephalopathy developed in 16 cases
      (28%). Because of slow progression, the exact beginning of the neurological
      symptoms was difficult to determine and varied from 7 to 11 years. The extent of
      the cerebral and endocrinological disturbances was very different but a marked
      effect of the optic nerve was not seen. It seems that the usual X-ray therapy
      with single doses of 1.8 Gy and total doses of 45-50 Gy have a high risk of
      radiogenic morbidity.

PMID- 8738493
TI  - LINAC-radiosurgery (LINAC-RS) in pituitary adenomas: preliminary results.
AB  - From 8/90 through 4/94, 32 consecutive patients with recurrent pituitary
      macroadenoma (PA) were treated with LINAC-RS after tumour resection and/or
      radiotherapy. Single doses ranging from 8-20 Gy (median: 14.5 Gy) were applied in
      14 patients with acromegaly, 5 with Cushing's disease, 4 with Nelson tumours, 5
      with prolactinomas and in 4 with nonfunctioning PA's. Retrospective analysis of
      26 patients with a follow-up of > or = 6 months revealed no significant
      endocrinologic response in patients with Cushing's disease, Nelson tumour or
      prolactinoma. In contrast in 12 evaluated patients with acromegaly within 6-36
      months after LINAC-RS the median GH-value decreased significantly. In 3
      nonfunctioning PA's a tumour volume reduction has been observed. We conclude,
      that LINAC-RS with moderate single doses might be a safe and beneficial treatment
      in patients with acromegaly or nonfunctioning PA's resistant to conventional
      therapy. In Cushing's disease, Nelson tumours or prolactinomas higher doses seem
      to be required.

PMID- 8738494
TI  - Comparison of thermoregulatory characteristics of patients with intra- and
      suprasellar pituitary adenomas.
AB  - Thermoregulatory capabilities under physiologic cold and heat exposure of 37
      patients with suprasellar pituitary adenomas (As) and 10 patients with
      intrasellar adenomas (Ai) were analyzed and compared to each other and to 13
      controls (Ctr.) In Ai no shift of the thermoregulatory threshold temperatures was
      observed. In As the regulation was shifted to a 0.5 degrees C higher mean body
      temperature in 82% of the patients, indicating a "set-point" elevation. The
      accuracy of the regulation against thermal loads was maintained, the velocity was
      reduced. Postoperative examination of As revealed a normalisation of the "set
      point". Modifications of the hypothalamic amine systems by the compressive effect
      of the suprasellar adenomas are discussed to be the most probable cause for the
      observed thermoregulatory alterations.

PMID- 8738495
TI  - The molecular biology of hormone and growth factor receptors in meningiomas.
AB  - Expression of a number of steroid hormone and growth factor receptors is
      characteristic of meningiomas. This paper reviews the analysis of receptors for
      progesterone, estrogen, androgen and platelet derived growth factor (PDGF) in
      human meningioma tissue specimens. Progesterone receptor was assessed by Northern
      blot analysis and immunohistochemistry in meningioma tissue specimens.
      Progesterone receptor mRNA was expressed in 64% of the meningiomas examined.
      Immunohistochemical data correlated well with the Northern blot analysis. The
      staining was clearly nuclear. Expression was more common in meningioma tissue
      from women than from men. Analysis of receptor expression in tissue culture
      derived from meningioma specimens demonstrated the loss of progesterone receptor
      within one to two passages. It was shown that the progesterone receptor mRNA
      expression which is present in meningiomas is functional by transfection
      techniques. The estrogen receptor was undetectable by Northern blot analysis; a
      small amount could be detected in meningioma tissue specimens by polymerase chain
      reaction (PCR). The androgen receptor was found in 67% of the specimens examined.
      Like the progesterone receptor, it was more common in women than in men (69% vs.
      31%). The immunohistochemical data correlated well with the Northern blot
      analysis, with the receptor predominantly found in the nucleus. Unlike
      progesterone receptor, androgen receptor expression was not lost in cell culture.
      The subunits for PDGF were expressed in various quantities in meningiomas. Only
      the PDGF beta-receptor (PDGFR-beta) not alpha-receptor, was found in meningioma
      tissue specimens. In contrast, the ligands PDGF A and PDGF B were expressed in
      all tumors. The functionality of the PDGF beta-R was determined by examining the
      induction of the protooncogene C-fos by PDGF BB in meningioma cell cultures. A
      significant increase in C-fos protein was observed with the addition of PDGF BB
      to meningioma cultures.

PMID- 8738496
TI  - Hormonal dependency of cerebral meningiomas.
AB  - Though meningiomas are benign intracranial tumors, a minor group invades the
      skull base and the connective tissue of the sinus cavernous inducing neurological
      deficits. These patients can not be cured by surgical treatment. Therefore, the
      development of an adjuvant medical therapy has been the goal during the last
      decade. We report here on different medical concepts which are based on steroids,
      amines, growth factor antagonists and cytokines. In addition, our data give
      evidence that the growth of intracranial meningiomas is under multifactorial
      proliferative control.

PMID- 8738497
TI  - Surgical treatment of meningiomas involving the cavernous sinus: evolving ideas
      based on a ten year experience.
AB  - The outcomes of 114 patients with meningiomas operated at the University of
      Pittsburgh were analyzed. Cerebrospinal fluid leakage was the most frequent
      complication, observed in 25 patients (21%). Complications were more frequent in
      patients who had recurrent (previously operated) tumors and patients with
      extensive tumors. Our current analysis also indicates that patients with prior
      radio-therapy (usually external beam) have unacceptably high complication rates
      after microsurgery. Early results indicate that regrowth rates are much higher in
      patients with incomplete resection (20%) than those with gross total excision
      (5%). Of the 114 patients, 108 returned to independent living and/or their
      previous occupation.

PMID- 8738498
TI  - Meningiomas involving the parasellar region.
AB  - The authors report on 180 cases of meningiomas involving the parasellar region,
      which have been surgically treated between 1978 and 1993. Most of the tumors
      originated in the middle cranial fossa (66%). Half of the patients had visual
      deficits, and palsy of the eye movements was observed in 25% of the cases.
      Depending on the tumor origin and extension, the surgical approach was chosen.
      Total tumor resection varied very much, depending mostly on the tumor extension,
      and the pattern of growth. The overall total resection (Simpson I-II) was 57%.
      The postoperative results were good in 77% of the cases, and surgical mortality
      was 3%.

PMID- 8738499
TI  - Atypical and malignant meningiomas: evaluation of different radiological criteria
      based on CT and MRI.
AB  - The following are our results of a retrospective analysis of 214 patients,
      operated on meningiomas, in order to investigate radiological criteria of
      malignancy. Among these cases there were 31 patients with a histologically
      confirmed diagnosis of malignant subtypes. As uncertain signs of malignancy of
      ensuing radiological features are an irregular enhancement of contrast-media and
      the size of cerebral edema. Based upon CT and MR images we have developed a
      standardised, computerised evaluation method which enables us to study in detail
      the internal architecture of meningiomas.

PMID- 8738500
TI  - Prognostic significance of nuclear DNA content in human meningiomas: a
      prospective study.
AB  - Flow cytometric DNA analyses were performed to study the correlation between
      alterations of nuclear DNA content and clinical aggressive tumour behaviour in
      134 cranial meningiomas. Forty-one meningiomas revealed an aneuploid DNA content
      with a distribution of n = 24 in benign, n = 12 in atypical and n = 5 in
      anaplastic tumours. Aneuploid DNA content was correlated with a significantly
      higher amount of histomorphological criteria like evidence of mitoses, necrosis,
      infiltration and increased cellularity. There was a significantly higher Ki 67
      proliferation index in the aneuploid meningiomas in comparison to the diploid
      tumour group. The rate of aneuploid cell-lines was increased in recurrent
      tumours. No tumour recurrence could be found in diploid meningiomas during follow
      up (mean 37 months, range 22-46 months). However eight of forty-one aneuploid
      tumours showed meningioma recurrence. Nuclear DNA content has an important
      significance in predicting risk of recurrence and poor clinical outcome after
      benign meningioma surgery.

PMID- 8738501
TI  - Correlation between cytogenetic and clinical findings in 215 human meningiomas.
AB  - The management of meningiomas remains a major challenge to the neurosurgeon
      because patients having this common benign tumor can be cured effectively by
      surgical resection. But there are a number of meningiomas that have an aggressive
      course and tend to recur. Predicting the recurrence of meningiomas has often been
      mentioned in the context of histology or surgical techniques and some approaches
      considered. However, the recurrence rate remains between 10% and 20%, even after
      total removal. To improve the care of patients with problematic meningiomas, 215
      different human meningiomas were collected between 1976 and 1993 and
      cytogenetically analyzed using standard techniques. 140 patients could be
      observed for 1 to 17 years after complete tumor removal, whereby 21 tumors (15%)
      displayed one or more recurrences during that long-term observation period. The
      tumors were classified according to different clonal abnormalities: we observed
      recurrence in 10 (9.1%) of 111 (79.2%) tumors having a normal karyotype or
      typical monosomy of chromosome 22, whereas 9 (69.7%) of 13 tumors with pronounced
      hypodiploidy and 3 (35%) of 8 tumors with a hyperdiploid karyotype recurred. A
      loss of the short arm of chromosome 1 was identified in 6 meningiomas with a
      recurrence rate of 60%. Our observations show that the correlation between
      meningiomas and recurrence is highly significant (p = 0.002) and that these
      tumors require special treatment in addition to surgical skill.

PMID- 8738502
TI  - Surgical results of spinal meningiomas.
AB  - We report on 94 spinal meningiomas in 88 patients operated between September 1977
      and August 1994 which were followed for up to 13 years (mean 24 +/- 35 months).
      Complete tumour resection led to postoperative improvement of every preoperative
      deficit or symptom. En plaque, recurrent, anterior, and low thoracic or lumbar
      meningiomas were likely to be resected incompletely. Partial tumour removal,
      arachnoid scarring, primary dural suture, recurrent meningiomas, and male sex
      were independent factors predisposing to clinical recurrence. Cauterization
      instead of resection of the tumor matrix was not associated with a higher
      recurrence rate.

PMID- 8738503
TI  - Microsurgical management of ventral and ventrolateral foramen magnum meningiomas.
AB  - The authors report their experiences gained from 19 patients with ventral or
      ventrolateral foramen magnum meningiomas operated on via the dorsolateral,
      suboccipital transcondylar access route. It is emphasized that the microsurgical
      management of these lesions includes two important aspects which increase the
      safety of the procedure: a meticulous preoperative planning based on the
      microanatomical details of each patient, as well as an individualized tailoring
      of the surgical approach. There were no deaths, and, in the past 5 years, no
      neurological complications in this series. Gross total removal of the tumour was
      achieved in each case. It is concluded that microsurgical removal of ventral or
      ventrolateral foramen magnum meningiomas with this technique constitutes a safe
      and recommendable procedure.

PMID- 8738504
TI  - Meningiomas of the cerebellopontine angle.
AB  - Meningiomas of the cerebellopontine angle (CPA) represent a clinically and
      surgically interesting entity. The opportunity of complete surgical excision and
      the incidence of impairment of nerval structures largely depend on the tumour
      biology that either leads to displacement of surrounding structures by an
      expansive type of growth or to an enveloping of nerval and vascular structures by
      an en plaque type of growth. As the origin and the direction of growth are very
      variable, the exact tumour extension in relation to the nerval structures and the
      tumour origin can be identified sometimes only at the time of surgery. Out of a
      series of 230 meningiomas of the posterior skull base operated between 1978 and
      1993, data of 134 meningiomas involving the cerebellopontine angle are presented.
      There were 20% male and 80% female patients, age at the time of surgery ranging
      from 18 to 76 years, on the average 51 years. The clinical presentation was
      characterized by a predominant disturbance of the cranial nerves V (19%), VII
      (11%), VIII (67%) and the caudal cranial nerves (6%) and signs of ataxia (28%).
      80% of the meningiomas were larger than 30 mm in diameter, 53% led to evident
      brainstem compression or dislocation and 85% extended anteriorly to the internal
      auditory canal. Using the lateral suboccipital approach in the majority of cases
      and a combined presigmoidal or combined suboccipital and subtemporal approaches
      in either sequence in 5%, complete tumour removal (Simpson I and II) was
      accomplished in 95% and subtotal tumour removal in 5%. Histologically the
      meningiotheliomatous type was most common (49%) followed by the mixed type (19%),
      fibroblastic (16%), psammomatous (7%), hemangioblastic (7%) and anaplastic (2%)
      types. Major post-operative complications were CSF leakage (8%) requiring
      surgical revision in 2% and hemorrhage (3%) requiring revision in 2%. While the
      majority of neurological disturbances showed signs of recovery, facial nerve
      paresis or paralysis was encountered in 17%, and facial nerve reconstruction was
      necessary in 7%. Hearing was preserved in 82% with improvement of hearing in 6%.
      The variability of tumour extension, the implications and limitations for
      complete surgical excision are discussed along with the experiences from the
      literature.

PMID- 8738505
TI  - Management of petroclival meningiomas: a critical analysis of surgical treatment.
AB  - Treatment of petroclival meningiomas have been a matter of discussion in
      neurosurgery. Since the advent of microsurgery, and with development of new skull
      base approaches more recently, the treatment of these tumours has become
      standardised, and the post-operative results considerably improved. However,
      potential complications have been related with the surgical removal of these
      lesions. The authors describe their experience and summarise the major reports of
      the literature on this subject.

PMID- 8738506
TI  - Symptomatology, surgical therapy and postoperative results of sphenoorbital,
      intraorbital-intracanalicular and optic sheath meningiomas.
AB  - A series of 7 patients with optic sheath meningiomas, 3 intracanalicular and
      intraorbital, 2 intraosseus meningiomas of the sphenoid wing involving the optic
      canal, and 4 sphenoorbital meningiomas were reported. The choice of a surgical
      approach to the orbit was appropriate to the location and size of the tumour
      relative to the optic nerve. The most common complaints were proptosis, reduction
      of visual acuity and paresis of eye muscles. Patients with optic sheath
      meningiomas are threatened postoperatively by visual loss whereas the high
      recurrence rate has to be taken into consideration in cases of sphenoorbital
      meningiomas.

PMID- 8738507
TI  - Factors influencing morbidity and mortality after cranial meningioma surgery--a
      multivariate analysis.
AB  - In a retrospective analysis 385 patients with a histologically defined cranial
      meningioma were studied to analyze the impact of characteristic factors on
      morbidity and mortality after modern cranial meningioma surgery. Mortality was
      4.2% one month and 7.3% six months after operation. 15.6% of the patients stayed
      more than one month in the hospital (defined as criteria of operative morbidity).
      Age, poor preoperative clinical condition (ASA score), intra- and postoperative
      bleeding and CSF disturbances were significantly associated with a subsequent
      decrease of quality of life. First symptoms like intracranial hypertension,
      seizures, aphasia and hemiparesis were correlated with an increase of
      postoperative Karnowsky index. Postoperative quality of life decreased in
      patients with optic and other cranial nerve disturbances significantly. Tumour
      size, location (exception: medial sphenoid wing) and histological diagnosis did
      not influence surgical outcome. This information may be useful in management
      decisions regarding asymptomatic meningiomas in elderly and high risk patients.

PMID- 8738508
TI  - Clinical relevance of somatostatin receptor scintigraphy in patients with skull
      base tumours.
AB  - The differential diagnosis of tumours in the skull base is often difficult. With
      the experience that various intracranial tumours differ in their expression of
      somatostatin binding sites (SBS) somatostatin receptor scintigraphy (SRS) with
      the somatostatin analogue octreotide can give additional information of the
      tumour entity. Seventy patients with various tumours of the skull base were
      examined with 111Indium-labelled DTPA-octreotide injected i.v.. Planar and
      tomographic images were obtained with a gamma camera 4-6 and 24 hours after
      injection. All of the meningiomas (unifocal and multifocal tumours in various
      locations) showed a high density of SBS whereas in none of the examined
      neurinomas SR were found. Pituitary adenomas revealed in only 50% SR in different
      concentrations and independent of the endocrine activity. SRS can help in the
      differential diagnosis between meningiomas and other tumours, postoperative scar
      or radionecrosis at the skull base. A dural infiltration with meningioma tissue
      ("meningeal sign") may be discriminated from a reactive hypervascularisation in
      lesions with a diameter > 0.5 cm. We conclude that SRS can offer additional
      diagnostic aspects in the pre- and postoperative management of patients with
      skull base tumours.

PMID- 8738509
TI  - Progesterone receptors in tumor fragment spheroids of human meningiomas.
AB  - Progesterone receptors (PgR) are detectable in about 60-70% of tissue specimens
      of human meningiomas. Despite these data, PgR are hardly to be found in monolayer
      tissue culture of meningiomas. Aim of this study was to elucidate whether PgR
      might be preserved in tumor fragment spheroids of meningiomas maintained in organ
      culture since the morphological appearance of the original tumor is preserved by
      this culture technique. Aliquots of meningioma specimens of 25 patients (17
      females) were snap frozen in liquid nitrogen immediately after removal.
      Additionally, monolayer tissue cultures of the same specimen were obtained as
      primary culture and passage #3. Tumor fragment spheroids were kept on medium-agar
      with liquid medium overlay and harvested after 1 and 3 weeks in culture. PgR were
      detected by immunohistochemistry using a rat monoclonal antibody. 18/25
      meningioma tissue specimens were positive for PgR. In 8 out of 15 PgR-positive
      tumors which formed spheroids we could detect PgR in fragment spheroids after 1
      and 3 weeks in culture. In contrast, none of the monolayers depicted PgR. PgR is
      preserved in a considerable amount of tumor fragment spheroids of PgR-positive
      meningiomas. They remain detectable after 3 weeks of culture whereas monolayer
      tissue cultures are PgR-negative. Thus, tumor fragment spheroids seem to be a
      suitable tool to investigate progesterone/antiprogesterone effects in vitro.

PMID- 8738510
TI  - PET-study of intracranial meningiomas: correlation with histopathology,
      cellularity and proliferation rate.
AB  - The glucose metabolism of 62 meningiomas was measured by fluorine -18-2
      fluorodeoxyglucose (FDG) PET and correlated with proliferation rate (Ki-67 index)
      and tumor cellularity. The mean metabolic rate (MRGlu) for meningiomas was 0.26
      +/- 0.13 mikromol/g/min (range 0.08-0.62 mikromol/g/min). The relative tumor FDG
      uptake (Q-MRGlu) (tumor/contralateral cortex) of all meningiomas was calculated
      with 0.73 +/- 0.37 (0.24-1.79). Differences of Q-MRGlu were significant between
      the groups with high vs. low cellularity (p < 0.01), increased vs. normal
      proliferation rate (p < 0.025) and low (WHO grade I) vs. higher (WHO grades II,
      III) graded tumors. In recurrent meningiomas (14 tumors) the glucose metabolism
      was not increased. The data show that 18 FDG-PET is suitable to serve as non
      invasive predictor of tumor growth characteristics in meningiomas.

PMID- 8738511
TI  - Biology of interleukin-5 and its relevance to allergic disease.

PMID- 8738512
TI  - Exposure chamber for allergen challenge. The development and validation of a new
      concept.
AB  - Exposure chambers have proven to be valuable tools in studying allergic diseases.
      The chamber provides a controlled environment and maintains conditions for
      measuring the amount of allergen inducing symptoms in allergic subjects. The aim
      of the present study was to develop and test an exposure chamber. The chamber was
      constructed as an airtight tent, made of transparent polyethylene, easy to adapt
      to the shape of an existing room, easy to clean, and providing exact allergen
      dosage control. Airflow to the interior of the tent was controlled by a variable
      inlet ventilator fitted with a micropore filter and balanced by a variable high
      volume air-sampler on the outlet side. Trace material and allergen were
      administered as aerosols with a nebulizer connected to the inlet pipe. Samples
      were obtained from interior surfaces and filters at the outlet. Two different
      methods were used to test the concept. One method used a colored, neutral trace
      substance (phenol red indicator) measured photometrically on extracts from
      filters. Secondly, house-dust mite allergen (Dermatophagoides pteronyssinus) was
      applied, with samples analyzed by an ELISA technique. The results demonstrated
      the ability of the system to administer and sample allergen with a high degree of
      reproducibility. A clinical pilot trial proved the capability of the system to
      initiate symptoms in allergic subjects.

PMID- 8738513
TI  - Allergen avoidance in infancy and allergy at 4 years of age.
AB  - In an attempt to prevent or reduce the manifestations of atopic disease, a group
      of infants considered to be genetically at high risk of atopy was entered in a
      prenatally randomized, controlled study. A prophylactic group (n = 58) was either
      breast-fed with their mothers excluding foods regarded as highly antigenic from
      their diets, or given an extensively hydrolysed formula. In addition, strenuous
      efforts were made to reduce exposure to the house-dust mite by application of
      acaricide to the bedroom and living room carpets and upholstered furniture. A
      control group (n = 62) was fed conventionally by breast or on formula, and no
      specific environmental measures were taken. The results (previously reported)
      after 1 year showed significantly less total allergy, asthma, and eczema in the
      prophylactic group. Similar results were obtained at 2 years although the
      reduction in asthma no longer achieved statistical significance. However, there
      was significantly less sensitization, as shown by a battery of skin prick tests
      (SPTs), to both dietary allergens and aeroallergens in the prophylactic group.
      All the children have now been reviewed at the age of 4 years, and SPTs to a wide
      range of dietary allergens and aeroallergens have been performed. The control
      group continues to show more total allergy (odds ratio [OR] 2.73, 95% confidence
      interval [CI] 1.21-6.13, P < 0.02), definite allergy (allergic symptoms plus
      positive SPT) (OR 5.6, CI 1.8-17.9, P < 0.005), and eczema (OR 3.4, CI 1.2-10.1,
      P < 0.05). More control children have positive SPTs (OR 3.7, CI 1.3-10.0, P <
      0.02). A dual approach to the prevention of allergic disease, avoiding as far as
      possible sensitization to food and aeroallergens, significantly reduces the risk
      of atopic disease. This should be reserved for infants considered at very high
      risk of atopy, and close medical and dietetic supervision must be available.

PMID- 8738514
TI  - Formaldehyde exposure enhances inhalative allergic sensitization in the guinea
      pig.
AB  - Formaldehyde (FA), a common indoor air pollutant, has been associated with
      increased prevalence rates of asthmatic symptoms among exposed individuals in
      epidemiologic surveys. We studied the influence of FA exposure on inhalative
      allergic sensitization in the guinea pig. Three groups of guinea pigs (n = 12
      each) were exposed to clean air or two different FA concentrations (0.13 and 0.25
      ppm) over 5 consecutive days. Exposure was followed by inhalation of 0.5%
      ovalbumin (OA) as sensitizing allergen. Three weeks later, specific bronchial
      provocation with OA was performed with body plethysmographic measurement of
      compressed air (CA). Furthermore, specific anti-OA-IgGl (reaginic) antibodies
      were determined in serum. In a further six animals, the respiratory tract was
      examined histologically for signs of inflammation directly after the end of FA or
      clean air exposure. In the group exposed to 0.25 ppm FA, 10/12 animals were found
      to be sensitized to OA (positive reaction on specific provocation) vs. 3/12
      animals in the control group (P < 0.01). Furthermore, CA measurements of specific
      bronchial provocation and serum anti-OA-antibodies were significantly higher in
      the 0.25 ppm FA group than in controls (CA 0.35 vs. 0.09 ml median, P < 0.01;
      anti-OA-IgGl 13 vs. < 10 EU median, P < 0.05), indicating enhanced sensitization.
      In the group exposed to 0.13 ppm FA, no significant difference was found compared
      to the control group. There was no sign of inflammation of the lower airways in
      FA-exposed guinea pigs other than mucosal edema, which was discovered by
      morphometry. We conclude that short-term exposure to a low concentration of FA
      (0.25 ppm) can significantly enhance sensitization to inhaled allergens in the
      guinea pig.

PMID- 8738515
TI  - Airway eosinophilic inflammation, epithelial damage, and bronchial
      hyperresponsiveness in patients with mild-moderate, stable asthma.
AB  - Allergic asthma is characterized by chronic recruitment of eosinophils in the
      airways. Once activated, eosinophils release toxic products, including eosinophil
      cationic protein (ECP), able to damage airway epithelial cells. To test the
      hypothesis that also in mild-moderate stable asthma, a significant eosinophil
      activation could occur, we studied 25 asthmatic patients (34 +/- 19 years old),
      of whom 18 were allergic (27 +/- 12 years) and seven nonallergic (42 +/- 10
      years), with FEV1 values > or = 70% of predicted, and eight normal volunteers
      (controls, 33 +/- 11 years). All subjects underwent methacholine (MCh) challenge
      on the first visit, and bronchoalveolar lavage (BAL) on the second visit
      (approximately 3-4 days later). BAL cells were counted and albumin (Alb) (as
      index of protein dilution in BAL fluid) and ECP levels (as index of eosinophil
      activation) in BAL fluid were measured. As compared to controls, a significant
      increase in BAL eosinophil and in BAL epithelial cell numbers was observed in
      asthmatic patients (P > 0.05, each comparison), with no differences between the
      two asthmatic patient subgroups. Detectable ECP levels (> 2 micrograms/1) were
      found in BAL of 18 asthmatic patients (14 allergic and four nonallergic asthmatic
      patients), while Alb levels were measurable in 25 BAL fluids and found to be
      similar in controls and asthmatic patients, and in the two asthmatic patient
      subgroups (P > 0.05, each comparison). In BAL of asthmatic patients, positive
      correlations were found between eosinophil numbers and 1) ECP/Alb levels (r =
      0.50, P = 0.020); 2) epithelial cell numbers (r = 0.50, P = 0.014). In asthmatic
      patients, a significant negative correlation was found between bronchial
      reactivity to MCh (log Pd15) and ECP/Alb levels in BAL fluid (r = -0.6, P =
      0.005), whereas no correlation was found between log Pd15 MCh and BAL eosinophil
      or epithelial cell number (P > 0.1, each correlation). These data suggest that
      bronchial eosinophil recruitment and activation may occur also in mild-moderate
      stable asthma and that bronchial epithelium damage and airway responsiveness may
      be partially associated with the eosinophilic inflammatory reaction.

PMID- 8738516
TI  - Possible induction of food allergy during mite immunotherapy.
AB  - Sera of 17 patients receiving immunotherapy for house-dust mite allergy were
      tested for IgE antibodies against snail and shrimp. Serum samples were taken at
      the start of immunotherapy and 14-20 months later. While the average IgE response
      to mite, Der p 1, and Der p 2 did not alter significantly, the average response
      to snail showed a significant increase. This included two conversions from
      negative to strongly positive. These novel IgE antibodies against snail were
      shown to be cross-reactive with mite. Three patients had a positive RAST for
      shrimp. For one of them, a strong increase of IgE against shrimp (and snail) was
      observed. In 2/3 snail/shrimp-positive sera, IgE antibodies against the cross
      reactive allergen tropomyosin from mite, snail, and shrimp were demonstrated. A
      clear IgE response to snail (> 10% binding in a snail RAST) was confirmed by a
      positive skin prick test (SPT) for 6/10 patients. The two patients with
      antitropomyosin IgE also had a positive SPT for shrimp, and demonstrated the oral
      allergy syndrome (OAS) after eating shrimp. The observations in this study
      indicate that house-dust mite immunotherapy is accompanied by the induction of
      IgE against foods, including tropomyosin-reactive IgE. Food allergy (OAS) was
      observed in patients that had IgE antibodies against this cross-reactive
      allergen. In conclusion, induction of IgE during mite immunotherapy might
      occasionally cause allergy to foods of invertebrate animal origin.

PMID- 8738517
TI  - Occupational IgE-mediated rhinitis caused by ninhydrin.
AB  - Ninhydrin is a laboratory chemical used as a reagent in the detection of free
      amino and carboxyl groups in proteins and peptides. We present the case of a
      laboratory technician who developed symptoms of rhinitis when handling papers
      immersed in a solution containing ninhydrin. Prick tests for ninhydrin and
      ninhydrin RAST were positive. The inhalation provocation test in an exposure
      chamber gave an immediate nasal response. A positive prick test to ninhydrin, an
      elevated level of specific IgE antibodies to ninhydrin, and the RAST inhibition
      test confirmed an IgE-mediated type I allergic reaction. We are not aware of any
      other report of ninhydrin as a cause of IgE-mediated allergy.

PMID- 8738518
TI  - Occupational asthma due to different spices.
AB  - We describe a 27-year-old subject who developed rhinitis and asthma symptoms 1
      year after starting to prepare a certain kind of sausage. He was previously
      diagnosed as having allergy to coconut, banana, and kiwi and allergic rhinitis to
      horse, cat, dog, and cow. A positive immediate skin prick test (SPT) for paprika
      (dry powder of Capsicum annuum [Solanaceae]), coriander (Coriandrum sativum
      [umbelliferous]), and mace (shell of nutmeg, Myristica fragrans [Myristicaceae])
      at a concentration of 10% (w/v) was obtained. SPT with other sausage ingredients,
      mites, pollens, and molds were negative. By ELISA, specific IgE antibodies to
      paprika, coriander, and mace were demonstrated. By ELISA-inhibition assays, a
      partial cross-reactivity was found among IgE-binding components from paprika and
      mace. The immunoblot analysis showed two IgE-reactive protein bands able to bind
      to IgE from mace of 20 and 40 kDa and two other bands from coriander extract of
      50 and 56 kDa. No bands were detected from paprika extract. Specific bronchial
      inhalation challenges showed an immediate asthmatic reaction to extracts from
      paprika, coriander, and mace with a maximum fall in FEV1 of 26%, 40%, and 31%,
      respectively, with no late asthmatic reactions. In summary, we demonstrate that
      inhalation of dust from paprika, coriander, and mace can result in an IgE
      mediated reaction to these spices. In this patient, occupational asthma was due
      to spices from botanically unrelated species.

PMID- 8738519
TI  - Delayed hypersensitivity reaction to paracetamol (acetaminophen).
AB  - We are reporting three patients who experienced delayed cutaneous reactions after
      treatment with paracetamol (acetaminophen). These reactions were confirmed in
      controlled challenge tests. Patch tests with paracetamol were positive in all
      patients. A biopsy performed of the case 1 patch test confirmed that the lesion
      was compatible with delayed hypersensitivity reaction-type allergic contact
      dermatitis.

PMID- 8738520
TI  - Eosinophil cationic protein serum levels and allergy in chronic fatigue syndrome.
AB  - Chronic fatigue syndrome (CFS) is a syndrome of uncertain etiopathogenesis
      characterized by disabling fatigue associated with a variable number of somatic
      and/or neuropsychologic symptoms. In patients with CFS, several immunologic
      abnormalities can be detected, including a higher prevalance of allergy. The aim
      of this study was to determine whether CFS patients, well studied for their
      allergy profile, show signs of eosinophil activation, as detectable by the
      measurement in serum of eosinophil cationic protein (ECP) levels. In 35
      consecutive CFS outpatients (diagnosis based on the Centers for Disease Control
      case definition), ECP was measured in serum by a competitive enzyme immunoassay
      (ECP-FEIA kit, Kabi Pharmacia Diagnostics, Uppsala, Sweden). Fourteen disease
      free subjects with no history of CFS or allergy were selected as controls. ECP
      serum levels were significantly higher in CFS patients than in controls (18.0 +/-
      11.3 micrograms/l vs 7.3 +/- 2.1 micrograms/l; P < 0.01). In the CFS population,
      the prevalence of RAST positivity to one or more allergens was 77%, while no
      control showed positive RAST. Twelve of the 14 CFS patients with increased ECP
      serum levels were RAST-positive. However, CFS RAST-positive patients had no
      significantly higher ECP serum levels than CFS RAST-negative patients (19.3 +/-
      12.4 micrograms/l vs 13.6 +/- 3.7 micrograms/l; P = 0.4). This is the first
      report of increased serum levels of ECP in CFS. On the basis of the available
      data, it is discussed whether eosinophil activation has a pathogenetic role in
      CFS or is linked to the frequently associated allergic condition, or, finally,
      whether a common immunologic background may exist for both atopy and CFS.

PMID- 8738521
TI  - Amount of pollen has an effect on the systemic and local levels of soluble ICAM-1
      in patients with seasonal allergic rhinitis.
AB  - We investigated whether the amount of antigen has an effect on the systemic and
      local levels of soluble ICAM-1 (sICAM-1) in patients with pollinosis, and
      assessed its biologic significance. The levels of subjective symptoms and sICAM-1
      in sera and nasal epithelial lining fluids (ELF) from 14 subjects with pollinosis
      (allergic group) and eight healthy subjects (control group) were measured from
      pre- to postseason in 1993 (total pollen count: 10,854/cm2) and 1994 (total
      pollen count: 415/cm2), and the results were compared with each other among the
      four groups. The levels of subjective symptoms and sICAM-1 in ELF from the
      allergic group significantly increased during the season in both 1993 and 1994.
      However, there was a significant difference (P < 0.01) between the levels of
      those in 1993 and those in 1994 during the season. The levels of sICAM-1 in sera
      from the allergic group were significantly upregulated during the seasons and
      postseasons only in 1993, and there was a significant difference (P < 0.05)
      between the levels in 1993 and those in 1994 during the postseason. We conclude
      that amount of pollen has an influence on the local and systemic levels of sICAM
      1, as well as the scores of subjective symptoms, in patients with seasonal
      allergic rhinitis.

PMID- 8738522
TI  - Local reaction to ocular disodium cromoglycate.

PMID- 8738523
TI  - Delayed hypersensitivity to penicillin.

PMID- 8738524
TI  - Anaphylaxis induced by streptomycin in cell media.

PMID- 8738525
TI  - Can inhalation of garlic dust cause asthma?

PMID- 8738526
TI  - Atopy and season of birth.

PMID- 8738527
TI  - Inhibition of nitric oxide synthesis does not improve interleukin-2-mediated
      antitumor effects in vivo.
AB  - Nitric oxide (NO) decreases cytotoxicity and proliferation of cytotoxic
      lymphocytes (CTLs) in vitro. Both can be prevented by inhibitors of the NO
      synthase (NOS). To elucidate whether inhibition of the IL-2-induced NOS could
      boost efficacy of IL-2-stimulated CTLs in vivo, we assessed lung metastases in
      mice injected with IL-2, the NOS inhibitor aminoguanidine (AG), their combination
      and the diluent. No improvement was observed for IL-2 + AG compared to IL-2 while
      NO production was normalized. Since NO causes one of the two major side effects
      of IL-2 treatment, hypotension, we further studied whether capillary leak could
      be attributed to NO, too. While IL-2-inducible NO was reduced to control levels
      by AG, pulmonary edema was unaffected. Thus a decrease in NO does not improve
      antitumor effects of IL-2-stimulated CTLs nor does it attenuate IL-2-associated
      capillary leak.

PMID- 8738528
TI  - Intraperitoneal cholelithiasis after laparoscopic cholecystectomy--behavior of
      'lost' concrements and their role in abscess formation.
AB  - In two experimental studies we sought preliminary information about the behavior
      of concrements lost in the peritoneal cavity during laparoscopic cholecystectomy.
      MATERIALS AND METHODS: In study 1, human gallstones were analyzed using X-ray
      diffraction, classified in three groups and examined with an ultramicroscope;
      then they were implanted in the peritoneal cavity of rats. After 8 weeks or 6
      months, the animals were sacrificed and the concrements analyzed again as before.
      The tissues surrounding the calculi were also examined histologically. In study
      2, human gallstones were examined with regard to bacterial contamination on the
      surface or in the middle of the calculi. The cholesterol content was analyzed,
      and the stones were divided into three groups and implantated in the rats as in
      the first study. After 8 weeks, the animals were sacrificed and areas with
      identifiable tissue reactions were examined histologically and microbiologically.
      RESULTS: The concrements lost their crystalline formation without any relation to
      their former cholesterol content, as shown by X-ray diffraction as well as
      ultramicroscopy. Mineralogically, these changes are a certain sign of structural
      dissolution. Cholesterol stones only caused abscess formations in association
      with gram-negative bowel germs. Sterile pigment concrements often led to a
      mesenchymal reaction such as granulomas. Contaminated pigment stones also
      resulted in extensive abscess formations.

PMID- 8738529
TI  - Expression of beta-2-integrins and L-selectin by leukocytes and changes in acute
      phase reactants in total hip replacement surgery.
AB  - The aim of this study was to characterize the changes in the quantitative
      expression of beta 2-integrins and L-selectin detected by means of fluorochrome
      conjugated monoclonal antibodies and flow cytometry on leukocytes in the systemic
      circulation after a major musculoskeletal trauma, i.e. hip replacement surgery,
      and to relate these changes to parameters of the acute-phase response [plasma
      acute-phase reactants (C-reactive protein, CRP, and interleukin-6, IL-6) and
      parameters of coagulation activation (thrombin-antithrombin III complexes, TAT)].
      Eight patients with either primary or secondary osteoarthritis of the hip
      received uncemented total hip prostheses. LFA-1 (CD11a/CD18) was upregulated on
      granulocytes during the operation. MAC-1 (CD11b/CD18) expression on monocytes
      increased to peak levels 20 h after surgery, whereas the L-selectin (CD62L)
      expression on monocytes and granulocytes reached peak values at the end of
      surgery. The changes in expression of LFA-1 on monocytes, MAC-1 on granulocytes
      and p150,95 (CD11c/CD18) on monocytes and granulocytes during and after the
      operation did not reach statistical significance. TAT and IL-6 increased during
      surgery and reached peak values at the end of the operation and 20 h after
      surgery, respectively. In contrast, CPR concentrations increased after surgery
      with peak levels 44 h postoperatively. Significant upregulation of LFA-1 on
      granulocytes and L-selectin on monocytes and granulocytes preceded the increase
      in IL-6 which again preceded the increase in CRP. However, the up- or
      downregulation of leukocyte beta 2-integrins and L-selectin during and after
      surgery was not significantly correlated with the increase in IL-6. The increases
      in TAT correlated well with the upregulation of L-selectin on monocytes, but not
      with the beta 2-integrins known to participate in the coagulation process in
      vitro. The rise in CRP was inversely correlated with the maximal increase in
      expression of MAC-1 on monocytes. In conclusion, the changes in leukocyte
      adhesion molecules during and after surgery indicate changes in critical
      leukocyte functions. The lack of correlation between quantitative up- and
      downregulation of leukocyte beta 2-integrins and parameters of the acute phase
      response suggests that these processes are regulated through independent pathways
      or that functional up- and downregulation of adhesion molecules, shedding,
      leukocyte-endothelial adhesion and mobilization of new unactivated cells may
      result in a net estimate of leukocyte activation not suspected to be positively
      correlated to acute-phase reactants.

PMID- 8738530
TI  - Effects of biliary obstruction on the endocytic activity in hepatocyte and liver
      sinusoidal endothelial cells in rats.
AB  - Obstructive jaundice impairs function in liver parenchymal and sinusoidal cells.
      In this study, the endocytic activity in sinusoidal endothelial cells in the rats
      with biliary obstruction was measured by plasma clearance of radiolabeled
      formaldehyde-treated bovine serum albumin. The endocytic activity in hepatocytes
      was also measured with asialofetuin. The clearance of asialofetuin significantly
      decreased after 1 week of biliary obstruction and the clearance was reduced to
      42% of the controls at 4 weeks. In contrast, the clearance of formaldehyde
      treated bovine serum albumin was essentially unchanged until 4 weeks of biliary
      obstruction. The maximal removal rate which was assessed by kinetic analysis of
      injected protein for formaldehyde-treated bovine serum albumin showed no
      significant decrease at 2 weeks compared with the controls, while that for
      asialofetuin was significantly decreased to 50% of the controls. These results
      suggest that the endocytosis of formaldehyde-treated bovine serum albumin in
      endothelial cells is maintained until the advanced stage of biliary obstruction,
      whereas the endocytic activity for asialofetuin in hepatocytes is impaired
      earlier.

PMID- 8738531
TI  - Hepatic adenine nucleotides and DNA synthesis during the regenerative and
      atrophic process of the liver lobes after selective portal vein ligation.
AB  - Selective portal vein occlusion prior to aggressive hepatic resection is now an
      alternative way to decrease postoperative morbidity and mortality rates. However,
      the detailed changes in the hepatic energy status and DNA synthesis rate in both
      portal vein ligated (PVL) and nonligated (PVNL) lobes of the liver are not clear.
      In rats, the portal branch that supplies 70% of the liver volume was ligated, and
      changes in arterial ketone body ratio (AKBR), liver weight, histology, DNA
      synthesis rate and adenine nucleotides of the PVL and PVNL liver lobes were
      determined before and 1, 2, 4 and 7 days after portal vein ligation, and compared
      with those in sham-operated rats. The weight of the PVL lobes decreased, while
      that of the PVNL lobes increased depending on time. The DNA synthesis rates of
      the PVNL lobes were significantly higher than those in sham-operated control
      liver during the first 4 days with the maximal value on the 2nd day, while those
      of PVL lobes were essentially similar to the control values. Energy charge (EC)
      in both PVL and PVNL lobes significantly decreased on day 1 and recovered
      gradually, but with less extent in the regenerating PVNL lobes. The
      concentrations of total adenine nucleotides (TAN) in both the PVL and PVNL lobes
      were essentially similar during the first 2 days, but became significantly lower
      in PVL lobes after day 4. A decrease in EC preceded an increase in DNA synthesis
      only in the PVNL lobes, in contrast to the PVL lobes. Mitosis of hepatocytes on
      day 2 and subsequently enlarged lobules with an increased number of hepatocytes
      were histologic features in the PVNL liver. The AKBR was not correlated with
      hepatic energy charge of the liver. In conclusion, PVNL liver regenerates
      preceded by a decrease in EC and a subsequent increase in DNA synthesis keeping
      TAN constant, while PVL liver becomes atrophic, with a similar change in EC of
      the PVNL liver but ultimately decreased TAN without any change in DNA synthesis.
      AKBR is not a parameter reflecting the hepatic EC after portal branch ligation.

PMID- 8738532
TI  - Simultaneous transplantation of isolated hepatocytes reduces rejection of small
      bowel allografts and improves survival in the rat.
AB  - Hepatocytes transplanted some days prior to vascularized allografts were shown to
      have the potential to prolong allograft survival in the rat. In the present
      study, hepatocytes and small bowel allografts were transplanted simultaneously in
      a Lewis (donor)-Brown Norway (recipient) rat model. 8-15 x 10(6) liver cells were
      injected into the spleen of small bowel recipients. The administration of at
      least 10 mg cyclosporine A (CyA)/kg over 3 days was necessary to prevent early
      rejection of hepatocytes. In groups simultaneously receiving hepatocytes, small
      bowel grafts and 10 mg CyA/kg over 3 days, a significant mitigation of rejection
      and a prolongation of survival was achieved, compared to groups receiving solely
      small bowel grafts and 10 mg CyA/kg over 3 days. We conclude that simultaneously
      transplanted hepatocytes exert a protective effect on a grafted organ from the
      same donor, provided that early rejection of hepatocytes is prevented by
      sufficient immunosuppression.

PMID- 8738533
TI  - Effects of experimental fat embolism on central hemodynamics and oxygenation in
      pigs.
AB  - Nine anesthetized and mechanically ventilated test pigs were intracavally infused
      with a 10% allogeneic bone marrows suspension at a dose of 100 mg/kg over 5 min;
      9 control pigs received saline. The cardiac index decreased slightly in the fat
      embolism animals. Left ventricular stroke work remained unchanged in both groups,
      whereas right ventricular stroke work rose in the fat embolism animals. Mean
      arterial pressure remained stationary in the test group but rose in the controls.
      Pulmonary capillary wedge pressure and central venous pressure rose slightly in
      the test group. After infusion of the bone marrow suspension, mean pulmonary
      arterial pressure, pulmonary vascular resistance, pulmonary shunt and
      alveoloarterial oxygen tension difference increased immediately and remained
      elevated throughout the study period. Simultaneously, arterial and mixed venous
      oxygen tension and hemoglobin oxygen saturation decreased. Arterial carbon
      dioxide tension and hematocrit remained stationary. The fat embolism animals
      developed gradual fever. In conclusion, increased mean pulmonary arterial
      pressure, pulmonary vascular resistance, pulmonary shunt and alveoloarterial
      oxygen tension difference proved to be useful early indicators of experimental
      fat embolism.

PMID- 8738534
TI  - Physiological implications of hyperbaric oxygen tensions in isolated limb
      perfusion using melphalan: a pilot study.
AB  - Controversy exists concerning the optimal pO2 of the perfusate during isolated
      limb perfusion (ILP) with melphalan. Therefore we studied the implications of
      hyperbaric oxygen tensions in the perfusate. In 12 consecutive patients,
      subcutaneous pO2 (Continucath 1000), tissue and tumor pH, and blood gas values
      were monitored throughout the ILP procedure. ILP started with an oxygen flow
      through the bubble oxygenator which was set routinely at one half of the flow of
      the perfusate; 30 min before the end of ILP, the oxygen flow was tripled. Mean
      arterial pO2 before and during ILP (before and after increasing the oxygen
      supply) was 19.4, 25.5 and 49.4 kPa, respectively. Mean subcutaneous pO2 values
      before, during (before and after increasing the oxygen supply), and post-ILP,
      were 7.4, 10.1, 16.3, and 9.1 kPa, respectively. Tissue pH values in the subcutis
      and muscle decreased during routine oxygen supply (p = 0.001); muscle pH moved
      towards starting values after increase of the oxygen supply (p = 0.011). In 4
      patients, tumor pH was recorded showing a rise after increasing the oxygen supply
      (from 7.10 to 7.22; p = 0.11). In conclusion, high pO2 in the perfusate improves
      muscle pH during ILP. However, a concomitant rise in tumor pH may unfavorably
      influence the therapeutic effect of ILP, as it has been shown that low pH
      increases the cytotoxicity of melphalan.

PMID- 8738535
TI  - Fluid kinetics in CAPD patients during dialysis with a bicarbonate-based
      hypoosmolar solution.
AB  - The magnitude of transcapillary backfiltration by the colloidosmotic pressure
      within the peritoneal capillaries compared to the effective lymphatic absorption
      was investigated in continuous ambulatory peritoneal dialysis patients. This was
      done during a 4-hour dwell period, using a hypoosmolar dialysis fluid (280
      mosm/kg H2O) in 8 patients and compared to 5 of these patients using a 1.36%
      glucose (GS; 324 mosm/kg H2O). The low molecular weight solute transport did not
      differ between the two solutions. The intraperitoneal dextran 70 concentration
      increased during the dwell with the hypoosmolar dialysis fluid (from 770 to 945
      mg/l; p = 0.000002) and decreased with the GS (from 859 to 719 mg/l; p = 0.007).
      With the GS the transcapillary ultrafiltration was directed towards the abdominal
      cavity during the dwell period. With the hypoosmolar fluid, the transcapillary
      ultrafiltration was continuously directed towards the circulation. In this
      solution, the magnitude of transcapillary backfiltration due to colloidosmotic
      pressure within the peritoneal capillaries was 0.4 +/- 0.1 ml/min. In conclusion,
      intraperitoneal markers can be used in continuous ambulatory peritoneal dialysis
      patients for determination of effective lymphatic absorption and transcapillary
      fluid passage in both transport directions.

PMID- 8738536
TI  - Local fibrinolysis in native arteriovenous fistulas of haemodialysis patients.
AB  - This study was designed to evaluate local alterations of the fibrinolytic process
      in patent-functional native arteriovenous fistulas of patients on maintenance
      haemodialysis. For this aim, the concentrations of the main components of the
      fibrinolytic system were determined in plasma samples taken simultaneously from
      arteriovenous fistulas and contralateral upper extremity concurrent large veins
      of haemodialysis patients. Twelve patients (6 women and 6 men, age 36 +/- 8
      years) with end-stage renal disease on maintenance haemodialysis and 15 non
      smoker healthy volunteers (8 women and 7 men, age 31 +/- 10 years) with normal
      renal function were included in the study. The fibrinolytic parameters, except
      alpha 2-antiplasmin, were found to be elevated in arteriovenous fistulas of
      haemodialysis patients as compared with opposite upper extremity large veins of
      the same patients (p < 0.005). Increments in fibrinolytic parameters including
      tissue plasminogen activator antigen, urokinase-type plasminogen activator
      antigen and activity, and plasminogen activity together with lower alpha 2
      antiplasmin levels favor activation of fibrinolysis, except for higher alpha 2
      macroglobulin concentrations, in arteriovenous fistula. The study suggests that
      the fibrinolytic process is locally activated in arteriovenous fistulas of
      haemodialysis patients.

PMID- 8738537
TI  - High frequency of marked hyperphosphatemia during intravenous calcitriol therapy
      in hemodialysis patients with refractory hyperparathyroidism.
AB  - Efficacy and safety of intermittent intravenous calcitriol therapy were studied
      in 8 chronic hemodialysis patients with marked hyperparathyroidism refractory to
      oral therapy with calcium salts and daily vitamin D. They were followed for 20
      weeks (32 weeks for 2 patients). At the start of the study, serum calcium was <
      2.65 mmol/l and phosphate levels were controlled with calcium-based binders only.
      The phosphate content of the prescribed diet (< 1 g/day) remained unchanged
      during the study, and a low-calcium dialysate was used (1.38 mmol/l). The initial
      postdialysis calcitriol dose was 1 microgram and was increased to 2 micrograms in
      6 patients. Intravenous calcitriol effectively improved hyperparathyroidism in 7
      patients, with a significant decrease of the intact parathyroid hormone level
      from 650 +/- 433 to 195 +/- 208 pg/ml (p < 0.05). Hypercalcemia > 2.7 mmol/l
      occurring in 3 patients was observed in only 11% of the weekly laboratory
      controls and always resolved rapidly. In contrast, hyperphosphatemia > or = 2.0
      mmol/l was observed in 7 patients and in 40% of the weekly laboratory controls.
      In 15% of the cases the phosphate values even exceeded 2.4 mmol/l. The phosphate
      binder therapy had to be intensified accordingly, not only by increasing the dose
      of calcium-based binders, but also by introducing aluminum salts in 6 patients.
      In summary, our data show that intravenously administered calcitriol is effective
      in the treatment of severe hyperparathyroidism in most hemodialysis patients
      resistant to oral therapy. However, its usefulness seems to be limited by
      frequency and severity of hyperphosphatemia, frequently necessitating additional
      prescription of aluminum-based binders. These undesirable secondary events may
      thus limit the long-term utility of intravenously administered calcitriol.

PMID- 8738538
TI  - Blood purification procedures for acute renal failure: convenient strategy
      related to clinical conditions.
AB  - The choice in the renal replacement therapy of acute renal failure (ARF) should
      match the patients' individual needs and the characteristics of available
      therapies. 141 ARF patients, 65 with "isolated' ARF (group I) and 76 with ARF in
      multiorgan failure (group II), have been treated. In 33 patients of group I
      standard bicarbonate hemodialysis was used, while acetate-free biofiltration was
      used for the others. In group II, 42 patients have been treated by continuous
      arteriovenous hemofiltration and 34 patients by daily recycled bicarbonate
      hemodialysis. Our data show that acetate-free biofiltration and bicarbonate
      dialysis were both highly dependable, but acetate-free biofiltration was better
      tolerated. Continuous arteriovenous hemofiltration is the method of choice in
      high-risk patients; daily bicarbonate hemodialysis is preferable only in patients
      with hemorrhagic diathesis. The average survival time is 55.2% with a
      statistically significant difference between groups I and II, while no difference
      has been observed within the same group according to the procedure.

PMID- 8738539
TI  - Scanning electron microscopic investigation of catheters for blood access.
AB  - Using blood-contacting catheters, infections, thromboses, and stenoses are among
      the most frequent complications. They are caused by surface properties of the
      basic material. Ion beam based processes such as ion implantation (silicone
      rubber) and ion beam assisted deposition (silver-based coatings) affect only the
      outer micron of the treated material surface; there is little effect on bulk
      properties. These processes were employed also in the production of large-bore
      catheters used for extra-corporeal detoxification. In a prospective study in 56
      patients, 72 large-bore catheters were inserted into the internal jugular and
      subclavian veins and investigated after removal for bacterial colonization using
      a scanning electron microscope. In 24 patients 30 surface-treated catheters (Spi
      Argent I n = 14; Spi-Silicone n = 16) were used. 42 untreated catheters used in
      32 patients served as controls. Bacterial colonization was observed in 8.9% in
      contrast to 38.1% in untreated catheters. The scanning electron microscopic
      investigations showed in all catheters a low thrombogenicity. The ion beam based
      processes make the surface-treated catheters thrombus and infection resistant.

PMID- 8738540
TI  - Antioxidant enzymes--superoxide dismutase and glutathione peroxidase--in
      haemodialyzed patients.
AB  - The biological effect of oxygen-reactive species controlled by antioxidant
      mechanisms are exerted on the basis of antioxidant enzymes and substrates. In
      this study, the activities of antioxidant enzymes-superoxide dismutase (SOD) and
      glutathione peroxidase (GPx)-were determined in the erythrocytes of patients on
      regular haemodialysis treatment. The SOD activity was significantly lower
      (1,810.38 +/- 609.85 vs. 2,347.13 +/- 502.51 U/g haemoglobin, p < 0.05, or 70.71
      +/- 11.50 vs. 100.13 +/- 24.28 mU/10(6) erythrocytes, p < 0.0001), as was the GPx
      activity (18.80 +/- 4.22 vs. 23.26 +/- 3.61 U/g haemoglobin, p < 0.01), when
      compared with the control group. A positive correlation between GPx activity and
      number of haemodialysis sessions was found (p = 0.0038), but no correlation
      between SOD activity and number of HD sessions. An inpaired antioxidant enzyme
      defence system, here represented by SOD and GPx levels, can potentiate injury
      caused by free radicals in haemodialysis patients.

PMID- 8738541
TI  - Lipoprotein abnormalities in chronic renal failure and dialysis patients.
AB  - Lipoprotein abnormalities are common in patients with chronic renal failure (CRF)
      on either dialysis or conservative therapy. In order to investigate the changes
      in lipid and apolipoprotein pattern from early CRF to dialysis treatment, plasma
      lipids with apoproteins AI, B, E, CII, CIII, CII/CIII ratio, E/CIII ratio,
      parathyroid hormone (PTH) and insulin levels were examined in 72 patients with
      different degrees of CRF and 31 patients on hemodialysis (HD), and compared the
      values of 28 controls. A significant decrease in the Apo CII/CIII ratio was the
      earliest lipoprotein abnormality to occur in CRF. Hypertriglyceridemia (HTG) with
      reduced high-density lipoprotein cholesterol levels, increased Apo CIII and
      decreased Apo E/Apo CIII ratio only occurred in more advanced renal failure
      (creatinine clearance < 31 ml/min). HD patients showed a general worsening of the
      lipoprotein profile with elevated Apo E levels and indirect evidence of remnant
      accumulation. While PTH did not have any significant influence on lipoprotein
      pattern, increased insulin levels during HD might partly account for the HTG of
      these patients. Our results point to elevated Apo CIII, reduced Apo CII/Apo CIII
      and Apo E/ Apo CIII ratios as typical features of uremic hyperlipidemia and show
      that a defective triglyceride removal is the major pathogenetic mechanism of
      uremic HTG. HD treatment seems generally to worsen the lipid and apolipoprotein
      pattern observed in the predialytic stage of CRF.

PMID- 8738542
TI  - Immaculate conceptions in sub-saharan Africa: exploratory analysis of
      inconsistencies in the timing of first sexual intercourse and first birth.
AB  - Survey data from a number of developing countries show that a considerable
      proportion of parous women report that they had their first birth one or more
      years before they first had sexual intercourse. In this paper, I use data from
      eight African Demographic and Health Surveys to explore factors that contribute
      to cross-national differentials in the prevalence of these "immaculate
      conceptions." The results suggest that this data problem results not only from
      recall errors, but also from the fact that some respondents misinterpret the
      question on first sexual intercourse and report their age at the onset of
      intercourse with either their first or current husband rather than their age at
      sexual initiation.

PMID- 8738543
TI  - Mating patterns of the Abbad tribe in Jordan.
AB  - The mating patterns of the Abbad tribe in Jordan are examined based on empirical
      data obtained from four male samples representing the different levels of the
      Abbad's substructure as well as on nonempirical information and pedigrees
      collected during field work. From the total matings in each sample, at least one
      third were first-cousin marriages, and some 90 per cent were marriages within the
      Abbad. The estimated inbreeding coefficient (mean F = 0.018) was relatively high.
      Relatedness, geographic locality, maternal links, and the type of economy are
      suggested as the factors which influenced the mating behavior of the Abbad. The
      study also indicates the vital role of matings in the formation and make-up of
      the tribe. The Abbad tribe could be described as an endogamic population
      consisting of more or less inbreeding subunits.

PMID- 8738544
TI  - Maternal determinants of birth weight: a population-based sample from Qingdao,
      China.
AB  - This analysis examines the relationship between maternal determinants and birth
      weight in a population-based birth cohort of 5,284 mothers with singleton births
      of 28 completed gestational weeks in Qingdao, China, in 1992. Multiple linear
      regression models suggest that the length of the menstrual cycle, age at
      menarche, maternal weight, maternal height, parity, and number of antenatal
      visits had independent effects on birth weight after controlling for gestational
      age and sex of infant. The estimated difference in mean birth weight for each
      year after menarche was 11.7 g (95 per cent CI 4.6-18.8), and for each day of the
      menstrual cycle was 4.0 g (95 per cent CI, 2.1-6.0), after controlling for
      gestational age, sex of infant, maternal height, maternal weight, parity and the
      number of antenatal visits. No substantial differences in determinants of birth
      weight were found between the sexes. Maternal age, education, and occupation
      failed to reveal any significant association with birth weight. In sum, those
      women who reached menarche younger and had a relatively short menstrual cycle had
      a heavier baby on average, and the determinants of birth weight did not differ
      between male and female in the cohort.

PMID- 8738545
TI  - How does childbearing affect fertility motivations and desires?
AB  - In this study we assume that fertility decisions are made one birth at a time and
      use longitudinal data collected from 401 married couples over a two-year period
      to explore how having a child affects two types of fertility motivation and three
      types of fertility desires. Using a series of five constrained multiple
      regression analyses, we tested the effects of two childbearing variables on these
      five types of motivation and desires in the context of a large set of control
      variables also hypothesized to affect fertility motivation and desires. The
      results demonstrate that the childbearing variables have a substantial effect in
      all five regression models. Specific findings indicate that childbearing
      stimulates greater positive motivation for childbearing and an increase in the
      number of children desired. Although this situation would appear to create a
      positive feedback loop in which each child born further increases the motivation
      and desire for children, the findings also suggest three different mechanisms
      whereby childbearing causes a counterbalancing regulation of that loop. These
      mechanisms include a negative motivation mechanism, a satiation mechanism, and a
      delay mechanism. The effect of these mechanisms on the termination of
      childbearing is considered in conjunction with a fourth mechanism, the
      achievement of desired family size.

PMID- 8738546
TI  - Men's desire for additional wives and children.
AB  - In sub-Saharan Africa, the majority of fertility and family planning studies are
      of women. By ignoring men, these studies overlook the primary fertility and
      family decision makers. This study uses male data from Cameroon to examine how
      currently monogamous men make fertility and nupital decisions. Three analyses are
      discussed. First, an analysis of monogamous men's desire for additional wives is
      presented. Second, an analysis of monogamous men's desire for additional children
      is presented. Finally, the two desires are examined simultaneously to disentangle
      the relationship between these two family desires. Three possible
      interrelationships between monogamous men's two family desires (desire for wives
      and desire for children) are examined and discussed. The results indicate that
      men's desire for more children drives their desire for additional wives and not
      the contrary. The implications of this finding for high fertility in areas where
      polygyny is common are discussed.

PMID- 8738547
TI  - Effects of multi-family housing on marital fertility in Iran: population policy
      implications.
AB  - The hypothesis of the relationship between housing types and fertility, which was
      originally developed and tested in Bogota, Colombia's housing study, is
      reexamined using Iranian data of urban married women of reproductive age. The
      findings of the study clearly and consistently show that women living in single
      family housing units have significantly higher actual and desired fertility than
      women living in multi-family housing units, regardless of their major social,
      economic and demographic differences. Furthermore, the analysis of the relative
      effects of socioeconomic and demographic variables on fertility indicate that
      housing types have greater effects on fertility than wife and husband's level of
      education, when the effects of other variables are controlled. This study implies
      that crowding and density, which generally are the outcome of high fertility, do
      have feedback effects causing fertility to decline. This provides some evidence
      for the hypothesis of self-generating fluctuations in population growth which
      maintains that a large population will face stiff economic competition, lower
      incomes, congestion and crowding if other means of production as well as social
      infrastructure do not expand simultaneously. Finally, this study suggests an
      optimistic sign of fertility reduction in the large urban populations where the
      single-family housing units are being replaced by multi-family housing units
      mainly because of high cost of land, material, and labor, and the shortage of
      housing units. Most of the large cities in Iran today fit the above descriptions.

PMID- 8738548
TI  - Hormonal and behavioral determinants of the secondary sex ratio.
AB  - The timing of insemination relative to ovulation and the frequency of
      insemination appear prominently in analyses of variations in human secondary sex
      ratios. Explanations invoking these variables are shown to be inadequate. A new
      synthetic model of sex determination is proposed in which the sex of offspring is
      powerfully determined by the state of the cervical mucus. The cervical state is
      then shown to be a function of hormonal factors endogenous to the female in
      interaction with the effects of previous inseminations.

PMID- 8738549
TI  - Malnutrition in children under five in Zimbabwe: effect of socioeconomic factors
      and disease.
AB  - Using data from the Zimbabwe Demographic and Health Survey (1988), this study
      investigates the factors that determine the nutritional status of children under
      five years of age. Several sociocultural, economic, and demographic variables
      were selected for the study. These independent variables were regressed against
      three proxy measures of malnutrition: height-for-age, weight-for-age, and weight
      for-height. The results show that the nutritional status of a child is determined
      by a variety of factors that are biological, social, cultural, and economic in
      nature, namely, birth status, birth weight, diarrhoeal status, duration of
      breastfeeding, and residence. The study concludes that most of the factors that
      account for malnutrition in children in Zimbabwe are preventable.

PMID- 8738550
TI  - Indirect estimation of cause of death structure in Africa and contemporary
      theories of mortality.
AB  - This paper is a critical assessment of techniques used for the estimation of
      cause of death structure in Africa in the light of contemporary theories of
      mortality. The technique mostly used for the indirect estimation of cause of
      death structure is based on the mortality experience in Western countries. With
      the marked differences in the epidemiologic transition experienced in Western
      countries and those being experienced in African countries, it is not very likely
      that an estimation of cause of death structure based on data from the former can
      accurately estimate cause of death structure in the latter. This argument is
      supported in the paper through a comparison of observed estimates of cause of
      death structure for some African populations with indirect estimates. It is
      proposed that a better approach is to use a residual method whereby one proceeds
      from nearly true estimates of cause of death rates to obtain estimates for
      unknown causes via the known general mortality.

PMID- 8738551
TI  - Son and daughter preferences in Benighat, Nepal: implications for fertility
      transition.
AB  - Married women in Benighat, Nepal stressed old age security and continuity of
      lineage as prominent reasons for wanting sons. In addition, women clearly desired
      daughters too--an important finding that is less often stressed. Religious
      reasons and help with household chores were the most common reasons reported for
      wanting a daughter. Strong desires for sons could increase fertility in settings
      where fertility is controlled. Additional desires for daughters could have an
      additional pronatalist influence. For Benighat we document a pervasive desire for
      at least two sons and at least one daughter. If realized, these sex composition
      preferences would increase fertility by 50 per cent. Actual effects are no doubt
      smaller, but the effects of sex preference on the desire for more children and on
      contraceptive use are clearly visible.

PMID- 8738552
TI  - Reliability versus validity of tests used in genetic identification.

PMID- 8738553
TI  - Vanadium: a review of the reproductive and developmental toxicity.
AB  - While the essentiality of vanadium for living organisms has yet to be established
      with certainty, vanadium has become an increasingly important environmental
      metal. Moreover, in recent years pharmacological interest in vanadium has also
      increased because of the hypothetical utilization of oral vanadium as an
      alternative therapy to parenteral insulin in diabetic patients. Adverse effects
      of vanadium depend on the circulating levels of this element. Among those
      effects, it is now well established that vanadate (V+5) and vanadyl (V+4) may be
      reproductive and developmental toxicants in mammals. Decreased fertility,
      embryolethality, fetotoxicity, and teratogenicity have been reported to occur in
      rats, mice, and hamsters following vanadium exposure. The reproductive vanadium
      toxicity, the maternal and embryo/fetal toxicity of this trace element, the
      perinatal and postnatal effects of vanadium, as well as the prevention by
      chelating agents of vanadium-induced developmental toxicity are reviewed here.
      The developmental effects of vanadium in pregnant diabetic rats are also
      summarized.

PMID- 8738554
TI  - Acute exposure of female hamsters to carbendazim (MBC) during meiosis results in
      aneuploid oocytes with subsequent arrest of embryonic cleavage and implantation.
AB  - A single oral dose of the fungicide and microtubule poison, MBC, administered to
      female hamsters at proestrus, results in infertility and early pregnancy loss
      (1). To characterize the site and mode of action of this effect, direct
      assessments of oocyte chromosomes, fertilization, and preimplantation embryo
      development were made. Female hamsters were given a single dose of MBC (1,000
      mg/kg) on the afternoon of proestrus (to coincide with meiotic maturation of the
      oocytes) and either killed shortly after ovulation (day 1) to recover oocytes, or
      bred and killed on gestation day (gd) 1 to 5 of pregnancy to assess fertilization
      and preimplantation embryo development and enumerate early implantation sites.
      Chromosome analysis in unfertilized oocytes revealed an MBC-induced increase in
      aneuploidy (37 vs. 14% in controls). When animals were bred after dosing, MBC had
      no effect on the number of oocytes recovered or fertilized. However, significant
      increases were found in the proportion of embryos that failed to reach the
      expected stage of development, namely, the eight-cell stage on the afternoon of
      gd 3, the morula stage by the morning of gd 4, and the blastocyst stage by the
      afternoon of gd 4 (a time when some embryos have implanted). The mean number of
      implantation sites, revealed by Evans Blue staining, was also significantly lower
      in treated females on the afternoon of gd 4 and the morning of gd 5. These simple
      direct assessments elucidated a mechanism of MBC-induced early pregnancy loss,
      induction of aneuploidy in oocytes. They also ruled out an effect on
      fertilization, but demonstrated a subsequent arrest of preimplantation embryonic
      development accompained by a decrease in the likelihood of implantation.

PMID- 8738556
TI  - An in vivo and in vitro investigation into the effects of alpha- chlorohydrin on
      sperm motility and correlation with fertility in the Han Wistar rat.
AB  - Following a recommendation from the International Conference on Harmonisation,
      pharmaceutical companies are now monitoring possible drug effects on sperm
      motility in the rat during preclinical safety studies by assessing sperm motility
      (velocity). However, it is not known precisely how changes in sperm motility
      relate to fertility. Therefore, the effects of alpha-chlorohydrin on sperm
      motility were investigated and related to fertility both in vivo and in vitro.
      alpha-Chlorohydrin was given orally to male rats using a range of doses: 0, 5,
      10, and 20 mg/kg for at least 5 consecutive days. Sperm were than assessed for
      motility using a standard scoring system (operators' observation of sperm) that
      graded degree of motility (i.e., 0 = i mmotile to 4 = very motile). The results
      showed a dose-related decrease in sperm motility. The sperm also appeared to move
      with a "jerky" action. Surprisingly, when this was correlated to fertility, none
      of the females mated with treated males became pregnant. A dose-related decrease
      in pregnancy would perhaps have been expected. There was no effect on sperm
      morphology, and testicular and epididymal pathology were only seen after doses of
      20 mg/kg. When sperm from untreated rats were incubated with alpha-chlorohydrin
      in vitro at concentrations of 0, 0.5, 1.0, and 1.5 mM, sperm motility and motion
      were similarly affected as observed in vivo. However, the fertilization capacity
      (in vitro fertilization) of the treated sperm showed a concentration-related
      reduction in percentage fertilization, and there was also evidence of abnormal
      embryo development. These findings suggest that the present standard scoring
      system used in preclinical safety studies is not a comprehensive indicator of
      sperm function and/or fertility. A better understanding of sperm movement,
      therefore, is desirable so effects on sperm motility can be related to fertility.

PMID- 8738555
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) modulates function of human
      luteinizing granulosa cells via cAMP signaling and early reduction of glucose
      transporting activity.
AB  - This study examined the changes in cellular glucose uptake, cAMP-dependent
      protein kinase (PKA), and progesterone production induced by 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) in human luteinizing granulosa cells (LGCs) in
      culture. The role of Ah receptor on TCDD-mediated toxicity in human LGCs was
      investigated. Treatment of human LGCs with TCDD produced a time- and dose
      dependent decrease in the cellular uptake of glucose. The Vmax and the K(m) of
      glucose transport were decreased by TCDD treatment. Furthermore, cytochalasin B,
      a specific inhibitor of facilitative glucose transporter proteins, totally
      abolished the portion of glucose transport activity that is sensitive to TCDD.
      Pretreatment of the cells with the Ah receptor blockers 4,7-phenanthroline and
      alpha-naphthoflavone antagonised the effect of TCDD on 3H-Me-glucose uptake.
      Structure-activity relationship studies with TCDD and three dioxin congeners
      revealed a rank order for their potency in the inhibition of glucose transport as
      follows: TCDD > 1,2,3,7,8-PCDD > 1,2,4,7,8-PCDD > 2,7-DCDD. Such a rank order is
      consistent with the previously determined biological activity of TCDD and the
      other dioxin congeners. Treatment of cells for 48 h with 10 nM TCDD substantially
      reduced PKA and progesterone production. The inhibitory effect of TCDD on
      progesterone production was more pronounced in the presence of insulin (10
      micrograms/mL) and D-glucose (13.3 mM). However, cytochalasin B abolished the
      effect of TCDD on progesterone production. Forskolin (adenylate cyclase
      activator) abolished the effect of TCDD on glucose uptake and progesterone
      production but it did not affect the action of TCDD on PKA activity. A
      relationship between glucose transporting activity and progesterone production in
      human LGCs treated with TCDD is indicated by several lines of evidence: a)
      cytochalasin B downregulated glucose transporting activity and progesterone
      production, b) insulin plus D-glucose downregulated glucose uptake and amplified
      the negative effect of TCDD on progesterone production, and c) forskolin
      abolished the negative effect of TCDD on glucose transporting activity and on
      progesterone production. From the present data we conclude that glucose
      transporting activity can be used as a sensitive biomarker to detect the very
      early response to TCDD in human steroid-producing cells and that effect of TCDD
      on steroid production is mediated through the cAMP-dependent protein kinase.

PMID- 8738557
TI  - Testicular degeneration induced in rat offspring by maternal treatment with
      sobuzoxane.
AB  - Pregnant rats were orally administered sobuzoxane (an antitumor drug) during
      various days of gestation and the testicular development of their offspring was
      examined histopathologically on day 21 after birth. When 15.6 to 250 mg/kg of
      sobuzoxane was given every day from day 7 to 17 of gestation, seminiferous
      tubules devoid of spermatogonia and/or spermatocytes were found in a dose related
      manner. The critical period for testicular degeneration was identified to be day
      13 and 14 of gestation by single administration experiments and single treatment
      with 15.6 to 250 mg/kg of sobuzoxane on day 14 of gestation gave a dose-dependent
      incidence of the tests abnormality. These results suggest that the testis
      abnormality in offspring from dams treated with sobuzoxane is due to inhibition
      of the proliferation of primordial germ cells during testis organogenesis.

PMID- 8738558
TI  - Neonatal mouse hip joint and hindlimb anomalies induced by prenatal exposure to
      Ara-C.
AB  - To induce hip joint anomalies and assess their relationship with hindlimb
      anomalies, pregnant mice (Jcl;ICR) were injected intraperitoneally with a single
      dose of 5.0 or 7.5 mg/kg of cytosine arabinoside (Ara-C) on dg 8, 9.5, or 11. On
      the 24th postnatal day, surviving offspring were stained by alizarin red S and
      anomalies were observed. Hip joint anomalies were observed only in one group
      exposed to 7.5 mg/kg on dg 9.5; the incidence of the hip joint anomalies in this
      group was about 30%. The types of hip anomalies observed were femoral shaft
      dysplasia, pseudoarthrosis of the femur, femoral head dysplasia, acetabular
      dysplasia, fusion between the femoral head and acetabulum, and pseudoarthrosis of
      the coxal bone. All of these anomalies were associated with preaxial hyperplasia
      of the hind paws and lower leg anomalies. Strangely, while newborns with no hip
      joint anomalies had a fairly high rate of oligodactyly, no newborn with hip joint
      anomalies had oligodactyly.

PMID- 8738559
TI  - Effects of postnatal exposure to cocaine on the development of the rat corpus
      callosum.
AB  - We investigated the effects of cocaine on the development of the corpus callosum
      in rats. From postnatal days 1 (P1) to 10 (birth = P0), cocaine (10 mg/kg) was
      subcutaneously injected in the pups, and saline, at the same volume, was
      administered to control pups. The animals were sacrificed at 110 days of age and
      a midsagittal section of the callosum was obtained. Morphometric measurement of
      the corpus callosum was performed in this section. In the control group, but not
      in the cocaine group, males had larger callosa than females. The cocaine
      treatment significantly decreased the total callosal area in male rats. These
      findings indicate that early postnatal cocaine abolishes the sexual
      differentiation of the corpus callosum.

PMID- 8738560
TI  - Embryotoxicity of polychlorinated biphenyls (PCBS) for preimplantation embryos.
AB  - In a previous study oral administration of a commercial PCB mixture (Aroclor
      1,260) to female rabbits (4 mg/kg b.wt. for 14 weeks) resulted in a significant
      accumulation of PCBs in 6-d-old blastocysts and increased preimplantation embryo
      mortality (1). In the present study, the direct toxicity of PCBs on
      preimplantation rabbit embryos was investigated during in vitro culture. One-day
      old cleavage stages and 3-d-old rabbit morulae were cultured in BSM II medium
      supplemented with 1.5% BSA in a reduced oxygen concentration of 5% O2. They were
      exposed to 50, 5, or 0.5 microgram Aroclor 1,260/mL culture medium for 24 h. PCB
      (50 micrograms) led to a complete degeneration of the exposed embryos. Following
      exposure to 5 micrograms only 16% of the morulae developed into blastocysts. The
      others were either arrested in the morulae stage or were degenerated. Cell
      proliferation of the nondegenerated embryos was approximately 20% of that of
      corresponding control embryos. Compared with nonexposed controls, addition of 0.5
      microgram PCB/mL showed either no or only a slight impairment of development.
      Preliminary embryo transfer experiments showed that morulae exposed to 5
      micrograms PCB with clear signs of degeneration after 24 h in vitro culture were
      able to implant. Aroclor 1,260 is embryotoxic in a dose-dependent manner in
      cultured rabbit preimplantation embryos.

PMID- 8738561
TI  - Sperm motion parameters in vas deferens and cauda epididymal rat sperm.
AB  - Motion parameters were compared in rat sperm isolated from the distal vas
      deferens and the cauda epididymidis. Motion parameters were also compared in 20
      microns and 50 microns deep muCellTM chambers using vas deferens sperm. Video
      recorded samples were analyzed manually for motility, and analyzed by a computer
      automated sperm analysis (CASA) system for motility, curvilinear velocity,
      linearity, mean and maximum amplitude of lateral head displacement (ALH), and
      beat/cross frequency using two versions of CellSoftTM (Series 3,000 and Series
      4,000). Motility, linearity, and beat/cross frequency were not significantly
      different between sperm from vas deferens and cauda epididymidis, while velocity
      and ALH values were slightly greater in sperm from vas deferens than from cauda
      epididymidis. Sperm motility and linearity were not significantly different when
      analyzed in 20 microns and 50 microns mu CellTM chambers. Velocity and ALH values
      were slightly greater in 20 microns than in 50 microns chambers, and beat/cross
      frequency was slightly lower in 20 microns than in 50 microns chambers. Sperm
      motility was significantly greater when determined manually than when determined
      with the Series 3,000 but manually determined sperm motility was only slightly
      greater than motility determined with the Series 4,000. Several sperm motion
      parameters differed significantly between the Series 3,000 and Series 4,000
      (curvilinear velocity, mean and maximum ALH, linearity, and beat/cross frequency)
      but the relative variability of the systems was comparable. Compared with manual
      determinations, the Series 3,000 overestimated and the Series 4,000
      underestimated the number of cells analyzed for motility. Therefore, differences
      existed between manual and CellSoft (Series 3,000 and 4,000) analysis of sperm
      motility and number of cells, and between CellSoft systems in the analysis of
      sperm motion parameters. However, only minimal differences in sperm motion
      parameters were observed between the vas deferens and cauda epididymidis, and
      between 20 microns and 50 microns deep muCell chambers.

PMID- 8738562
TI  - Methods for assessing sperm motility, morphology, and counts in the rat, rabbit,
      and dog: a consensus report. ILSI Risk Science Institute Expert Working Group on
      Sperm Evaluation.
AB  - Reproductive toxicity studies are increasingly including assessments of sperm
      parameters including motility, morphology, and counts. While these assessments
      can provide valuable information for the determination of potential reproductive
      toxicity, the methods for conducting the assessments have not been well developed
      in all laboratories and are continually evolving. The use of different methods in
      different laboratories makes comparison of data among laboratories difficult. To
      address the differences in methods, a working group was convened to discuss
      methods currently in use, share data, and try to reach consensus about optimal
      methods for assessing sperm parameters in rats, rabbits, and dogs. This article
      presents the consensus report, as well as future research needs, with the hope
      that optimized common methods will aid in the detection of reproductive effects
      and enhance interlaboratory comparisons.

PMID- 8738564
TI  - Establishment and characterization of a novel human promonocytic cell line from
      peripheral blood of a patient with psoriasis.
AB  - Human monocyte/macrophage lineages have unique phagocytic and immune-regulatory
      functions. We established a promonocytic cell line from the peripheral blood of a
      patient with psoriasis vulgaris. The newly established cells, termed YAP cells,
      grew in a suspension culture. In Wright-Giemsa-stained preparations, YAP cells
      were round or polygonal in shape. Transmission electron microscopy showed that
      the cells had clear nuclei with well-defined nucleoli. There were frequent
      mitochondria, a relatively abundant endoplasmic reticulum profile, free ribosomes
      and an occasional Golgi apparatus. Cytochemical studies showed a positive
      reaction for alpha-naphthyl butyrate esterase, which was completely inhibited by
      sodium fluoride, a diffuse positive reaction for periodic acid-Schiff, and a
      negative result for alkaline phosphatase and peroxidase. A large population of
      YAP cells reacted with the CD4, CD11b, CD25 and CD33 surface markers, but not
      with CD2, CD3, CD8 or CD19. We also found that YAP cells produced considerable
      amounts of TNF alpha, which was detected in the culture supernatant when the
      cells were treated with 1 ng/ml 12-O-tetradecanoylphorbol-13-acetate (TPA).
      Chromosome analyses showed that YAP cells contained a variety of marker
      chromosomes. It should be stressed that YAP cells were derived from a patient
      with a non-neoplastic disorder, whereas most monocytic cell lines previously
      reported are of malignant origin. This newly established cell line might be
      valuable for studying the pathogenesis of psoriasis, especially the role of
      monocytes/macrophages in the aetiology of the disease.

PMID- 8738563
TI  - LTA4 hydrolase in human skin: decreased activity, but normal concentration in
      lesional psoriatic skin. Evidence for different LTA4 hydrolase activity in human
      lymphocytes and human skin.
AB  - Leukotriene A4 (LTA4) hydrolase which transforms LTA4 into the proinflammatory
      compound LTB4 has been identified in human epidermis. The purpose of this study
      was to investigate the potential role of this enzyme in psoriasis, in which LTB4
      is present in biologically active concentrations. The concentration and activity
      of LTA4 hydrolase was determined in normal skin and in matched samples of
      involved and uninvolved psoriatic skin. The enzyme content was determined using
      an affinity-purified antibody. This antibody was also used for
      immunohistochemical staining of skin biopsies. Immunohistochemically LTA4
      hydrolase was localized predominantly in the basal and spinous layers in normal
      skin and in involved and uninvolved psoriatic skin. The LTA4 hydrolase content
      varied between 2.8 and 3.1 micrograms enzyme/mg protein and was found to be
      similar in normal and psoriatic skin, involved as well as uninvolved. In
      contrast, the activity of the enzyme was decreased significantly in involved
      psoriatic skin (9.9 +/- 2.1 micrograms LTB4/mg enzyme per min) compared with
      matched uninvolved psoriatic skin (16.4 +/- 3.5 micrograms LTB4/mg enzyme per
      min), but was decreased only insignificantly compared with normal skin (12.4 +/-
      1.8 micrograms LTB4/mg enzyme per min). It was found that the conversion of LTA4
      to LTB4 results in inactivation of LTA4 hydrolase activity. This finding is
      compatible with the idea that the decreased LTA4 hydrolase activity in involved
      psoriatic skin reflects transcellular LTB4 formation in vivo. In peripheral
      lymphocytes the enzyme content was 1.3 +/- 0.3 microgram enzyme/mg protein in
      normal lymphocytes and 1.4 +/- 0.3 microgram enzyme/mg protein in psoriatic
      lymphocytes, which was significantly lower than in the skin. In contrast, the
      specific LTA4 hydrolase activities in normal and psoriatic lymphocytes (23.4 +/-
      1.3 and 21.3 +/- 1.7 micrograms LTB4/mg enzyme per min) were significantly higher
      than in normal skin. These findings may indicate the existence of LTA4 hydrolase
      isoforms in human lymphocytes and human skin.

PMID- 8738565
TI  - The epidermal hyperplasia associated with repeated barrier disruption by acetone
      treatment or tape stripping cannot be attributed to increased water loss.

PMID- 8738566
TI  - Immunolocalizations of human gelatinase (type IV collagenase, MMP-9) and TIMP
      (tissue inhibitor of metalloproteinases) in normal epidermis and some epidermal
      tumors.
AB  - The matrix metalloproteinases (MMPs) MMP-2 and MMP-9 (gelatinases) have been
      suggested as serving an important role in cleaving the basement membrane
      structure. Tissue inhibitors of metalloproteinases TIMPs (particularly TIMP-1)
      are known to inhibit MMPs. Based on this background, we raised monoclonal
      antibodies against human gelatinase (MMP-9) and human recombinant TIMP (TIMP-1),
      and immunostained these two components in skin from patients with squamous cell
      carcinoma (SCC), Bowen's disease (BD) and keratoacanthoma (KA). MMP-9 showed
      positive staining mainly in the granular layer of normal epidermis. In some cases
      of SCC and BD, MMP-9 showed positive staining in the dysplastic lesions even in
      the basal layer. TIMP showed a thorough positivity in normal epidermis. Unstained
      regions with this antibody were observed in SCC and BD. These results suggest
      that an altered staining pattern for MMP-9 and TIMP may be closely related to the
      malignant transformation of SCC and BD.

PMID- 8738567
TI  - Effect of topically applied menthol on thermal, pain and itch sensations and
      biophysical properties of the skin.
AB  - The effect of menthol and alcohol as its vehicle on thermal sensations, pain,
      experimental itch and irritation were studied in 18 subjects, using a
      computerized thermal sensory analyzer, laser Doppler flowmetry and an
      evaporimeter for transepidermal water loss (TEWL). Menthol had a subjective
      cooling effect lasting up to 70 min in 12/18 subjects; however, it did not affect
      cold and heat threshold, nor did it affect cold and heat pain threshold. Alcohol
      produced an immediate cold sensation lasting up to 5 min in 4/18 subjects and
      lowered the sensitivity of cold sensation threshold (P < 0.05). Histamine
      injection did not change thermal and pain thresholds. Menthol did not alleviate
      histamine-induced itch magnitude, nor its duration. Following histamine
      injection, cold sensation median threshold decreased by 1.2 degrees C from (29.9
      degrees C to 28.7 degrees C) on the site treated with menthol (P < 0.01) with
      similar changes in thresholds at the alcohol-treated site (P < 0.05). Warm
      sensation and pain threshold in subjects receiving histamine injections, measured
      after menthol and alcohol application, did not differ from their baseline values
      with histamine alone. TEWL at the site treated with menthol was significantly
      higher (P < 0.05) than at the alcohol-treated and the control site (P < 0.01),
      suggesting that menthol has a higher skin irritating effect, or at least alters
      the stratum corneum water permeability. Our results suggest that menthol fulfills
      the definition of a counterirritant, but does not affect histamine-induced itch,
      nor does it affect pain sensation.

PMID- 8738568
TI  - Prolonged nuclear accumulation of p53 in xeroderma pigmentosum complementation
      group A cells after ultraviolet irradiation.

PMID- 8738569
TI  - Immunohistochemical study of HSP-70 in two basic leprosy groups.

PMID- 8738570
TI  - MHC class II+ keratinocytes from IFN gamma-treated human skin activate T cells in
      the presence of staphylococcal superantigen despite UVB irradiation.

PMID- 8738571
TI  - Apoptosis identified with DNA fragmentation in basal cell carcinomas.

PMID- 8738572
TI  - Vitamin D inhibits endothelial cell migration.

PMID- 8738573
TI  - FGF5 and the murine hair cycle.

PMID- 8738574
TI  - Upregulated expression of Fas antigen on cultured human keratinocytes with
      induction of apoptosis by cisplatin.

PMID- 8738575
TI  - The expression of alpha 6 and beta 4 integrin genes are differentially regulated
      by all-trans-retinoic acid (RA) in cultured human keratinocytes.

PMID- 8738576
TI  - Quantitative RT-PCR for neuroendocrine studies. A minireview.
AB  - Determination of mRNA levels of specific genes is becoming increasingly important
      as a measure of gene expression. With the recent advent of RT-PCR, the
      sensitivity for mRNA determination has been increased dramatically, and this
      technique is becoming widely used in neuroendocrine studies which involve small
      tissue samples and/or isolated nuclei. Nevertheless, the exact procedure for
      reliable quantification of RT-PCR has been widely debated. This minireview
      attempts to assimilate the available literature on the RT-PCR technique and
      discuss the various approaches commonly used to obtain quantitative results using
      the technique. An example from our laboratory of the use of RT-PCR for the
      measurement of several gene products in the same sample using exogenous internal
      standards is also provided. Particular attention is paid to the choice of
      endogenous vs. exogenous internal standards, the length of the transcript of the
      standard and its relationship to the target sequence being amplified, the
      amplification pattern of the target gene and internal standard, the
      reproducibility of the method, and the overall usefulness and suitability of RT
      PCR for neuroendocrine studies.

PMID- 8738577
TI  - Gonadotropin-releasing hormone neuroblasts from one olfactory placode can be
      present in both hemispheres in the clawed toad Xenopus laevis.
AB  - Ontogenetic differentiation of the GnRH-immunoreactive (GnRHir) neuron system was
      studied in the clawed toad Xenopus laevis by immunocytochemistry employing
      polyclonal antibodies against mammalian GnRH and chicken type II GnRH, and
      monoclonal antibodies against GnRH exhibiting wide cross-reactivity over animal
      classes. Toads at different stages of differentiation as well as postmetamorphic
      toads subjected to uni- or bilateral ablation of the olfactory placode (OPX)
      between developmental stages 25 and 30 were studied. GnRHir neurons and nerve
      fibers could not be detected before metamorphosis. Following metamorphosis, at
      stage 65-66, hemi-OPX toads did not exhibit any side differences in the number
      and overall distribution of the GnRHir neuronal structures; however, the total
      number of GnRHir neurons was approximately 50% of that counted in intact controls
      at the same developmental stages. These findings indicate that GnRHir neuroblasts
      differentiating on one side in the olfactory placode can appear on both sides of
      the brain in the course of their migration.

PMID- 8738578
TI  - Different serotonin receptor types participate in 5-hydroxytryptophan-induced
      gonadotropins and prolactin release in the female infantile rat.
AB  - Serotonin (5-HT) receptors can be classified into at least three, possibly up to
      seven, classes of receptors. They comprise the 5-HT1, 5-HT2, and 5-HT3 classes,
      the "uncloned' 5-HT4 receptor and the recombinant receptors 5-ht5, 5-ht6 and 5
      ht7. We investigated the role of different serotonin receptor types in a
      neuroendocrine response to the activation of the serotonergic system. Female
      immature rats were chosen as an experimental model as it has been shown that
      during the 3rd week of life, and not at later developmental stages, 5
      hydroxytryptophan (5-HTP, a serotonin precursor) induces gonadotropin release in
      females and not in males. Besides, at this age, serotonin releases prolactin in
      both sexes. 5-HTP (50 mg/kg) released prolactin, luteinizing hormone (LH) and
      follicle-stimulating hormone (FSH) as expected. Ketanserin (5-HT2A antagonist)
      and methysergide (5-HT2C antagonist) blocked 5-HTP-induced prolactin release, but
      did not block the LH or FSH responses. Ondansetron (5-HT3 receptor antagonist)
      did not modify prolactin response to 5-HTP, whereas it blocked 5-HTP-induced LH
      and FSH release. Propranolol (5-HT1 and beta-adrenergic antagonist) blocked
      prolactin, LH and FSH release induced by 5-HTP. The 5-HT2C agonist 1-(3
      chlorophenyl)piperazine dihydrochloride released prolactin, without modifying LH
      or FSH release. Methyl-quipazine and phenylbiguanide (5-HT3 agonists) increased
      both LH and FSH levels, without altering prolactin secretion. The present
      experiments indicate that serotonin acting at the 5-HT3 receptor mediates LH and
      FSH release in infantile female rats, whereas 5-HT2C or 2A receptor types
      participate in the release of prolactin at this age. 5-HT1 receptor type may be
      involved in the release of the three hormones, though a beta-adrenergic component
      of the response cannot be discarded.

PMID- 8738579
TI  - Distribution of prolactin receptors in the rat forebrain. Immunohistochemical
      study.
AB  - The distribution of prolactin receptors (PRL-R) in the rat brain was investigated
      for the first time with the immunohistochemical technique using monoclonal
      antibodies raised against PRL-R purified from rat liver. Granular immunostaining
      was observed in neurons and along their dendritic processes and fibers. PRL-R
      like immunoreactive neurons were found in a number of brain areas. There was a
      very dense labelling in the cerebral cortex (pyramidal cell layer), septal
      nuclei, amygdaloid complex as well as in the hypothalamus (suprachiasmatic,
      supraoptic, paraventricular and dorsomedial nuclei). A dense staining was seen in
      the substantia nigra, habenula and in the paraventricular thalamic nucleus.
      Immunostaining was also found in the choroid plexus and in the subcommissural
      organ. Comparison between the present distribution and that of PRL-like
      immunoreactivity indicates that the density of PRL-R generally corresponds to
      that of the fibers. However, in some regions densely stained by PRL-R antibody,
      there are very few PRL-immunoreactive fibers. These results are suggestive of
      different modes of action of PRL in the brain.

PMID- 8738580
TI  - Adenohypophysial allografts releasing prolactin decrease prolactin mRNA
      concentration in the host hamster's adenohypophysis in situ.
AB  - The inhibitory effects of pituitary allografts on the prolactin (PRL)-secretory
      system are presumed to be consequences of the unabated release of PRL by the
      allografts. In the present studies we used pituitary allografts in the Golden
      Syrian hamster to address the following questions: (a) Do allografts of adult
      adenohypophysial tissue which elevate serum PRL levels decrease the concentration
      of PRL mRNA in the host's adenohypophysis? (b) Is this effect shared by
      allografts of neonatal hypophysial tissue or neonatal muscle tissue which do not
      elevate serum PRL levels? (c) Do any of these types of allograft alter growth
      hormone mRNA in the host's adenohypophysis? Prolactin mRNA concentration, but not
      growth hormone mRNA concentration, was decreased in the adenohypophyses in situ
      in the hosts bearing adult adenohypophysial allografts in which serum PRL levels
      were elevated. In contrast, serum PRL in hosts with neonatal hypophysial or
      muscle allografts were not elevated and PRL mRNA levels in the adenohypophysis in
      situ were not decreased when compared to the levels measured in hamsters with
      sham transplants. Prolactin mRNA levels in hosts with neonatal muscle allografts
      were not different from levels in hosts with neonatal hypophysial allografts but
      were increased when compared to the levels measured in hamsters with sham
      transplants. There were no differences in PRL concentration in the
      adenohypophyses in situ between any of the groups. Also, PRL concentrations in
      neonatal hypophysial allografts were similar to those in adult adenohypophysial
      allografts. To our knowledge these observations are the first demonstrating that
      short-loop feed-back of PRL includes a decrease in PRL mRNA concentration. The
      observations also support the working hypothesis that PRL and not another
      pituitary factor exerts the negative feedback.

PMID- 8738581
TI  - Size and charge heterogeneity of pituitary and plasma prolactin in the male rat.
AB  - Although pituitary prolactin (PRL) exhibits size and charge variability,
      questions concerning the structural heterogeneity and biological potency of
      hormonal forms secreted in vivo remain. In the present studies, monomeric PRL in
      male rat pituitaries and plasma was fractionated by Sephacryl S-100 size
      exclusion chromatography and aqueous chromatofocusing to resolve size and charge
      forms under conditions compatible with optimum preservation of biological
      activity. Individual hormonal variants were subsequently evaluated for their
      ability to stimulate the growth of PRL receptor-bearing rat lymphoma cells in
      vitro. Pituitary elution profiles contained several cross-reactive size variants
      ranging from 30.4 to 21.5 kD in M(r); major hormonal peaks were eluted at 25.6,
      24.3, and 23.6 kD. Multiple size forms of PRL were also detected in plasma
      profiles, with predominant peaks eluting between 26.5 and 21.5 kD M(r) in size.
      Mean B/I ratios, established as an index of relative biopotency, varied
      significantly between size variants obtained from pituitary and plasma. Pituitary
      PRL size variants of 27.1, 24.3, and 21.5 kD exhibited greatest potency in the in
      vitro bioassay, whereas the 25.6- and 23.6-kD forms were least potent under these
      conditions. Of the PRL size variants detected in peripheral plasma, those of 24.3
      and 21.5 kD size were characterized by highest mean B/I ratios. Pituitary 24.3-kD
      PRL was chromatofocused as five charge variants of pI 5.34, 5.31, 5.26, 5.20, and
      5.14; only some of these isomers are apparently secreted in vivo, since pI values
      for plasma charge isomers ranged from 5.26 to 5.14. Charge isomers of pituitary
      24.3-kD PRL exerted variable mitogenicity in the Nb2 in vitro bioassay. The
      highest mean B/I ratio was associated with the relatively basic 24.3-kD isomer of
      pI 5.31; the relative biopotency of more acidic charge isomers was progressively
      diminished with increasing acidic charge. In summary, the present findings show
      that both size and charge variants of male rat pituitary PRL exhibit differential
      biopotency in vitro, indicative of their functional heterogeneity. The
      demonstration of multiple hormonal forms in peripheral plasma suggests that the
      net biopotency of circulating PRL reflects the sum of activity of structurally
      and functionally diverse molecules.

PMID- 8738582
TI  - Nitric oxide synthesis inhibitors prevent rapid behavioral effects of
      corticosterone in rats.
AB  - Corticosteroid actions at the brain can modulate neural function and behavioral
      processes. Classic corticosteroid effects are mediated through intracellular
      receptors which act primarily by regulation of DNA transcription. However, an
      alternative nongenomic mechanism mediating rapid corticosteroid actions by
      effecting the neuronal membrane has also been proposed. We have recently
      described a behavioral model of rapid corticosterone effects fulfilling criteria
      for considering nongenomic steroid actions, such as resistance to protein
      synthesis inhibition and to blockage of intracellular receptors through the use
      of specific receptor antagonists. The model consists of a rapid increase induced
      by a corticosterone injection (within 7.5 min of a systemic injection) on the
      locomotor response displayed by rats in a novel environment. In the present
      study, we aimed to study whether the gas molecule nitric oxide might be included
      among the effector systems involved in such rapid corticosterone effect. The
      administration of nitric oxide synthase inhibitors, given either systemically [NG
      nitro-L-arginine methyl ester (L-NAME), 30 mg/kg body weight, i.p.] or centrally
      [N-nitro-L-arginine (N-Arg), 10 microliters of a 10-mM solution i.c.v.],
      prevented the increase in locomotion induced by corticosterone (Cort, 5 mg/kg
      body weight i.p.). Specificity of this effect was supported by the ability of the
      nitric oxide precursor L-arginine (L-Arg, 350 mg/kg body weight i.p.) to inhibit
      L-NAME action. This effect of nitric oxide synthase inhibition on steroid effects
      was shown to be task-specific, since L-NAME failed to influence another rapid
      behavioral effect of corticosterone, the suppression of the acoustic startle
      response. Under our experimental conditions, corticosterone failed to affect
      peripheral blood pressure, discarding that the antagonistic effect of nitric
      oxide synthase inhibition on the corticosterone-induced effect in locomotion were
      related to a peripheral action at the cardiovascular level. Therefore, these data
      suggest a role for nitric oxide on the neurochemical mechanisms elicited by
      corticosterone to rapidly enhance locomotion in a novel situation.

PMID- 8738583
TI  - Activation of noradrenergic neurons in the locus coeruleus by corticotropin
      releasing factor. A microdialysis study.
AB  - In the present study the effects of different doses of corticotropin-releasing
      factor (CRF) and the CRF antagonist alpha-helical CRF on locus coeruleus (LC)
      neurons were studied in anesthetized male Wistar rats. To monitor the release of
      noradrenaline (NA) and its metabolite 3-methoxy-4-hydroxyphenylethylene glycol
      (MHPG), a microdialysis probe was implanted into the parietal cortex, a major
      projection area of the LC. Saline, 0.17, 0.51 nmol CRF and a combination of 5.1
      nmol alpha-helical CRF and 0.51 nmol CRF were applied to the LC via a fused
      silica capillary. While both doses of CRF augmented NA in parietal cortex
      dialysates (0.51 nmol CRF: from 0.0206 to 0.0266 pmol/sample; 0.17 nmol CRF: from
      0.0147 to 0.0170 pmol/sample), saline did not affect NA concentration. The
      metabolite MHPG also increased, but in a more prolonged time course. The
      antagonist alpha-helical CRF attenuated the CRF effects. The increase of
      extraneuronal NA concentration monitored in the cortical samples indicates an
      augmented depolarization rate of noradrenergic LC neurons. This clearly
      demonstrates the activation of these neurons by CRF, suggesting physiological
      interactions of CRF and noradrenergic neurons.

PMID- 8738584
TI  - Beta-adrenoceptor antagonists suppress elevation in body temperature and increase
      in plasma IL-6 in rats exposed to open field.
AB  - The purpose of these studies was to assess the involvement of beta-adrenoceptors
      in the development of psychological stress-induced elevation in body temperature
      (Tb) and rise in circulating interleukin-6 (IL-6). We selected three drugs to
      attempt to block the rise in body temperature and plasma IL-6; L-propranolol, D
      propranolol and nadolol. Both stereoisomers of propranolol have "local
      anesthetic' membrane-stabilizing activity and are capable of penetrating into the
      brain. However, D-propranolol has significantly lower beta-blocking activity than
      L-propranolol. Nadolol has beta-blocking activity similar to L-propranolol
      without membrane-stabilizing activity. Furthermore, nadolol does not cross the
      blood-brain barrier. All beta-blockers were injected intraperitoneally (i.p. 7.5
      mg/kg) or into the third cerebral ventricle (i.c.v., 5 or 50 micrograms/animal),
      20 min or just before exposure of rats to an open field, respectively. Blood
      samples for measurement of plasma IL-6 activity (IL-6-dependent B9 cell bioassay)
      were taken from rats immediately following exposure to the open field. After
      exposure to the open field, rats not treated with beta-blockers responded with a
      rapid rise in Tb measured by biotelemetry as well as with an increase in plasma
      IL-6 activity. The increase in Tb of open field-exposed rats was significantly
      suppressed by L-propranolol injected i.p. (delta Tmax = 0.14 +/- 0.15 degrees C
      for L-propranolol vs. 0.78 +/- 0.15 degrees C for vehicle-treated rats). Neither
      i.p. injection of D-propranolol nor nadolol had any effect on the increase in Tb
      induced by exposure to the open field. Both i.c.v. doses of L-propranolol and
      nadolol markedly attenuated the open field-induced rise in Tb. The large i.c.v.
      dose of D-propranolol (50 micrograms) did, whereas the lower dose (5 micrograms)
      did not suppress the elevation in Tb in open field exposed rats. The open field
      exposed rats injected with L-propranolol (both i.p. or i.c.v.) had lower plasma
      IL-6 activity than that of open field-exposed rats injected with vehicle (for
      i.p. injection: 5.2 +/- 1.3 U/ml for L-propranolol vs. 17.4 +/- 3.8 U/ml for
      vehicle; for i.c.v. injection: 3.5 +/- 2.3 U/ml for L-propranolol vs. 24.4 +/-
      7.2 U/ml for vehicle). Nadolol blocked the open field-induced rise in plasma IL-6
      only when injected i.c.v. but no i.p. Neither i.p. nor i.c.v. D-propranolol
      injection had an effect on plasma IL-6 activity in open field-exposed rats. These
      data show that beta-adrenoceptors in the central nervous system are involved in
      the psychological stress-induced elevation in Tb and rise in plasma IL-6 activity
      caused by exposure to an open field.

PMID- 8738585
TI  - Adenylate-cyclase-dependent pituitary adrenocorticotropin secretion is defective
      in the inflammatory-disease-susceptible Lewis rat.
AB  - Susceptibility to arthritis in the Lewis rat is associated with a defect of the
      hypothalamic-pituitary-adrenal axis. We examined the pituitary corticotropes of
      both intact and dexamethasone-treated male and female inflammatory-disease
      susceptible Lewis and inflammatory-disease-resistant Fischer rats. We determined
      adrenocorticotropin levels in the media from primary cultures of anterior
      pituitary cells of both strains. In other experiments we have measured
      intracellular cyclic adenosine monophosphate and inositol monophosphate
      accumulation. Cells were incubated with corticotropin-releasing hormone, arginine
      vasopressin, forskolin, phorbol myristate acetate, or thyrotropin-releasing
      hormone. Corticotropin-releasing hormone stimulated adrenocorticotropin secretion
      from both male and female Lewis rat pituitary cells in a concentration-dependent
      manner. Basal and stimulated adrenocorticotropin levels in cells from Lewis rats
      were lower than those measured in the incubation media of Fischer rat dispersed
      pituitary cells. Arginine vasopressin, as well as forskolin and phorbol myristate
      acetate, induced a significant release of adrenocorticotropin from pituitary
      cells of both strains. Incubation with corticotropin-releasing hormone did not
      produce a significant accumulation of intracellular cyclic adenosine
      monophosphate in Lewis rat dispersed pituicytes of both sexes. On the other hand,
      forskolin induced a significant increase of intracellular cyclic adenosine
      monophosphate in the same cultures. Finally, inositol monophosphate accumulation
      was comparable in pituitary cells from both Lewis and Fischer rats of both sexes
      incubated with thyrotropin-releasing hormone. Adrenocorticotropin secretion from
      pituitary cells of male Lewis rats treated in vivo with dexamethasone was either
      reduced or abolished following incubation with different secretagogues. A defect
      in pituitary adrenocorticotropin secretion could be among the causes of the
      hyporesponsiveness of the hypothalamic-pituitary-adrenal axis in the Lewis rat.
      Such a defect appears to be associated with dysfunction of receptor-coupled
      events related to adenylate cyclase.

PMID- 8738586
TI  - Can the haemorrhagic component of heparin be identified? Or an attempt at clean
      thinking on a dirty drug.
AB  - Heparin consists of different classes of molecules. We distinguish below-critical
      chain length heparin (BCLM, MW < 5,400), with only anti-factor Xa activity and
      above-critical-chain length material (ACLM, MW > 5,400) with both antithrombin
      and anti-factor Xa activity. In this article we introduce a division within the
      ACLM fraction, between extra large material (MW > 8,000) and ACLM-low (MW 5,400
      8,000). Extra large material is abundantly present in unfractionated heparin but
      is rare in low-molecular-weight (LMW) heparins. We noted that injection of an LMW
      heparin causes 5- to 10-fold higher plasma levels of ACLM than injection of a
      clinically equivalent dose of unfractionated heparin (UFH) and proportionally
      higher inhibitions of the clotting system. So with LMW heparin one can afford
      higher levels of anticoagulation than with UFH at a lower risk of bleeding. We
      surmise that this is caused by the virtual absence of the (haemorrhagic) extra
      large-molecular-weight fraction from LMW heparins. A laboratory artefact, i.e.
      the absence of Ca2+ in the anti-factor Xa tests, makes that heparin mixtures that
      lack extra large heparin molecules show a (spuriously) high ratio of anti-factor
      Xa activity over anti-thrombin activity. So the correlation between a high
      aXa/alla ratio and a favourable ratio of antithrombotic effect over bleeding is
      not necessarily caused by the presence of BCLM. In fact BCLM is a poor
      anticoagulant; in mixtures of ACLM and BCLM, ACLM causes by far the larger part
      of the anticoagulant effect. We surmise that the LMW fraction of ACLM is the
      active anticoagulant component in any heparin preparation and, isolated, would
      make a proper third-generation heparin.

PMID- 8738587
TI  - Subcutaneous low-molecular-weight heparin versus standard heparin and the
      prevention of thromboembolism in medical inpatients. The Heparin Study in
      Internal Medicine Group.
AB  - In a multicenter, double-blind clinical trial in 1,968 inpatients 1 daily
      subcutaneous administration of LMW heparin plus 2 placebo injections or 3 x 5,000
      IU unfractionated (UF) heparin was given for 10 (8-11) days. The primary end
      point was the incidence of proximal deep-vein thrombosis or pulmonary embolism.
      Patients were assessed during the study period for development of proximal deep
      vein thrombosis by compression sonography at days 1 and 10 and for pulmonary
      embolism by scintigraphy in symptomatic patients. Aim of the study was to
      demonstrate the equivalence of both treatment regimens. A total of 1,968 patients
      were randomized to receive UF or LMW heparin. Of these, 378 patients were
      excluded during the study period, so that 780 patients on UF and 810 on LMW
      heparin were included in the efficacy analysis. Four primary end points were
      observed with UF and 6 with LMW heparin, demonstrating the equivalence of
      treatments (p = 0.012). Additionally, pulmonary embolism was suspected as the
      cause of death in 6 patients who died during the study (3 per treatment group). A
      higher frequency of death (n = 32) was observed in the LMW-heparin group (p =
      0.02) particularly documented in a part of the centers. Safety analysis showed a
      higher frequency of local pruritus, local erythema and subcutaneous hematoma, a
      higher increase in plasma levels of triglycerides, total cholesterol, alanine
      aminotransferase and aspartate aminotransferase, and a decrease of antithrombin
      III in patients receiving UF heparin. A decrease in platelet count (values
      ranging between 40,000 and 80,000/microliter) was observed in 4 patients with UF
      and in none with LMW heparin. No severe thrombocytopenia was observed.
      Subcutaneous LMW heparin is as effective as UF heparin for prophylaxis of
      thromboembolism in bedridden, hospitalized medical patients.

PMID- 8738589
TI  - Protective effects of ticlopidine and aspirin, administered alone and in
      combination, on thrombus formation in rat cerebral vessels.
AB  - The protective effects of ticlopidine and d,l-lysine acetylsalicylate (L-ASA),
      used alone and in combination, on the pathogenesis of thrombosis in cerebral
      blood vessels were investigated in a rat animal model using a He-Ne laser method.
      Ticlopidine and L-ASA, given orally at a concentration from 100 mg/kg, inhibited
      thrombus formation in a dose-dependent manner. Ticlopidine (300 mg/kg p.o.)
      inhibited thrombosis in arterioles and venules for 3 days after administration.
      The inhibitory activity of L-ASA (300 mg/kg p.o.) was less prolonged than that of
      ticlopidine and was observed for only approximately 24 h. Combined administration
      of ticlopidine and L-ASA significantly enhanced and prolonged the antithrombotic
      effects of either drug given alone. The results demonstrate that ticlopidine and
      L-ASA have potent antithrombotic properties in rat cerebral blood vessels in
      vivo.

PMID- 8738588
TI  - A recombinant hirudin (IK-HIR02) in healthy volunteers. I. Effects on coagulation
      parameters and bleeding time.
AB  - The pharmacodynamic effects of different intravenous and subcutaneous doses of a
      recombinant hirudin (r-hirudin; IK-HIR02) on clotting parameters and bleeding
      time were investigated in 24 healthy volunteers in a bicenter study. Single
      intravenous bolus injections of 0.1, 0.2 and 0.3 mg/ kg IK-HIR02 caused a
      prolongation of thrombin time (TT) and aPTT in a dose-dependent manner and led to
      an increase in hirudin plasma levels > 6 micrograms/ml. The plasma half-life of
      IK-HIR02 was calculated as 1.3 h. A continuous infusion of 0.03 mg/kg/h of IK
      HIR02 for 4 h significantly prolonged TT and aPTT. At the end of the hirudin
      infusion, a mean plasma level of 0.19 +/- 0.13 microgram/ml was measured. Single
      subcutaneous doses of 0.1, 0.25 and 0.5 mg/kg markedly prolonged the coagulation
      tests. The highest increase in hirudin plasma levels was found 2 h after
      injection. At this time the aPTT was doubled after 0.5 mg/kg. After repeat
      subcutaneous injections of 0.3 mg/kg b.i.d., aPTT was doubled, and TT increased
      to about 200 s, 2 h after the injections. At this time the mean plasma level was
      0.5-0.6 microgram/ml. There was no cumulative effect after multiple injections.
      Bleeding time was not changed after the 4-hour intravenous infusion and after
      repeat subcutaneous injections of 0.3 mg/kg IK-HIR02. Bleeding time was
      moderately but significantly prolonged after the highest single intravenous and
      subcutaneous hirudin doses tested. Other than very minor local bleeding in some
      volunteers, IK-HIR02 was well tolerated. Biochemical blood and urine parameters
      did not change. In conclusion, r-hirudin (IK-HIR02) obtained by a new technique
      was well tolerated in healthy volunteers after single intravenous and
      subcutaneous injections, after repeat subcutaneous doses and during continuous
      intravenous infusion. Measurement of aPTT and anti-IIa activity, using a
      chromogenic substrate test, can be used to monitor hirudin effects if doses
      similar to those tested here are administered.

PMID- 8738590
TI  - Procoagulant activity of mononuclear cells is increased in myeloproliferative and
      myelodysplastic diseases.
AB  - Procoagulant activity (PCA) of peripheral mononuclear cells (PMC) was evaluated
      in patients with primary thrombocythemia (PT, group A), polycythemia vera (PV),
      idiopathic myelofibrosis (IM) and myelodysplastic syndromes (group B), and in 15
      healthy subjects as control group. PCA of PMC was assayed under basal conditions
      and after agonist-induced stimulation: bacterial lipopolysaccharide, glycosylated
      granulocyte-macrophage colony-stimulating factor, recombinant alpha-interferon.
      PCA was similar in the control group and group A when no stimulation was used,
      while PCA was found significantly higher in group B patients in the same
      conditions. In group A patients and in the control group, but not in group B
      patients, a lower PCA expression was found when PMC were simultaneously
      coincubated with LPS and alpha-interferon with respect to LPS incubation alone.

PMID- 8738591
TI  - Preoperative platelet count and postoperative blood loss in patients undergoing
      hip surgery: an inverse correlation.
AB  - In a previous study we tried to assess the clinical usefulness of platelet count
      (PlC) to confirm whether postoperative pulmonary embolism could be suspected
      early. Unexpectedly, the 19 patients who subsequently developed pulmonary
      embolism had significantly lower mean PlC levels even before surgery. In an
      attempt to discover whether the preoperative PlC levels were associated with a
      different incidence of postoperative blood loss, we decided to retrospectively
      study the relationship between preoperative PlC levels and the consequences of
      blood loss. There were 459 consecutive patients undergoing hip surgery. After
      excluding 5 patients who died during the first 3 postoperative days, and 16
      patients who bled from a definitive anatomic site, there were 438 patients. Blood
      loss was considered to be excessive when two or more of the following conditions
      were present: (1) total transfusion requirements exceeding 1,000 ml whole blood
      or 2 units of packed red cells; (2) a drop in hemoglobin level of 5 g/dl or more,
      and (3) a hemoglobin level below 8 g/dl at any moment during the first 8
      postoperative days. Blood loss was considered to be excessive in 91 patients.
      Preoperative PlC levels were significantly lower in these patients as compared to
      patients without the condition (204 +/- 52 vs. 236 +/- 79 x 10(9) liter-1; p =
      0.0002). When patients were classified according to the quartiles of preoperative
      PlC, the odds ratio of developing excessive blood loss was 0.69 (95% CI: 0.38
      1.26) in patients in the second quartile; 0.57 (95% CI: 0.30-1.06) in the third
      quartile, and 0.27 (95% CI: 0.13-0.57) in patients in the highest quartile. After
      adjusting for age, sex, type of surgery and type of prophylaxis, the preoperative
      PlC levels maintained a statistically significant inverse correlation with
      postoperative blood loss.

PMID- 8738592
TI  - Quantification of hemostatic proteins and activation products in synovial fluids
      from arthritic joints prior to and after induction of chemical synoviorthesis.
AB  - Synovial fluids drawn from joints of patients suffering from rheumatoid arthritis
      were investigated for their concentrations of proteins and activation markers of
      the complement, coagulation and fibrinolytic systems. A broad spectrum of
      plasmatic inhibitors and other hemostatic proteins were detectable by immunologic
      assays. Compared to normal plasma concentration ranges, levels of alpha 2
      antiplasmin, antithrombin III, heparin-cofactor II, factor H, alpha 2
      macroglobulin, inter-alpha-trypsin inhibitor, fibrinogen and particularly high
      molecular weight kininogen were found to be decreased when corrected for total
      protein content. However, highly elevated levels of C-reactive protein, factor
      XIII, PMN-elastase, prothrombin fragment F1+2, thrombin-antithrombin III, plasmin
      antiplasmin and terminal complement-complexes as well as C5a were determined.
      Eight and 24 hours after induction of chemical synoviorthesis, a general increase
      in most of the parameters was observed. Statistically significant alterations
      were found for C1-inhibitor, factor H, alpha 1-antitrypsin, inter-alpha-trypsin
      inhibitor, factor XIII, protein C, thrombin-antithrombin III complexes and C5a.

PMID- 8738593
TI  - Comparison of fibrinogen determinations.

PMID- 8738594
TI  - Abdominal surgery alters the calibration of bioimpedance cardiac output
      measurement.
AB  - The performance of impedance cardiography (TEBco), using the BoMed NCCOM3-R7S,
      and thermodilution (TDco) were compared in eight patients during major abdominal
      surgery. An opioid, volatile and relaxant anaesthetic technique was employed.
      This was supplemented with an epidural in five cases. Sets of three cardiac
      output readings, for both methods, were made at 10-20 min intervals throughout
      surgery. Data were compared using the Bland and Altman method, regression
      analysis and a nested model to measure variance components at different stages of
      surgery. Data from 157 sets of readings are presented. Agreement between the two
      devices was poor, with a ratio of TDco/TEBco of 115% and limits of agreement of
      51-193%. The regression line was TDco = (0.98) x TEBco-0.95 with r = 0.60. A more
      detailed analysis, using nested data, showed good repeatability with coefficients
      of variation of 5.4% for TDco and 4.8% for TEBco. During surgery shifts in the
      bias between the two devices occurred, which were related to changes in surgical
      conditions. Between shifts both devices showed good repeatability over time.
      Variance components were 0.27 within nested data and 0.082 between bias shifts,
      with a significantly greater overall component of 1.2 (ANOVA; P = 0.0001). Shifts
      could be explained by deficiencies in the algorithm used to calculate TEBco.
      Current TEBco technology is too inaccurate for intra-operative use. However,
      under stable operating conditions TEBco and TDco showed good repeatability.

PMID- 8738596
TI  - Limited applicability of the DATEX Reloxograph in diabetics with peripheral
      polyneuropathy.
AB  - The aim of the study was to investigate whether peripheral nerve dysfunction can
      influence the applicability of the DATEX Relaxograph in diabetics. Sixty two
      patients (43 diabetics, 19 non-diabetics) undergoing ophthalmosurgical procedures
      under general anesthesia were tested. The distal motor latency (DML) of the ulnar
      nerve served as a graduation tool for peripheral nerve dysfunction. The patients
      were divided in three groups: non-diabetics (group 1), diabetics with DML < 3.8
      msec (group 2), diabetics with DML > 3.8 msec (group 3). Relaxometry was
      performed by stimulating the right ulnar nerve near the wrist, and the evoked
      response (EMG) was obtained from the hypothenar muscle. Calibration of the device
      (i.e. supramaximal stimulation within the given current range of a maximum of 70
      mA) was carried out successfully in most patients of group 1 and 2 (94.7% and
      85.7% respectively). In contrast to that calibration could be carried out in only
      40.9% of the patients of group 3 (P < 0.01 vs. group 1 and 2). Consequently in a
      high percentage (59.1%) of the patients of group 3 relaxometry had to be
      performed in an uncalibrated manner. The results substantiate the hypothesis that
      peripheral nerve dysfunction can restrict the applicability of the Relaxograph in
      diabetics.

PMID- 8738597
TI  - Possibilities of classification of topographically distributed neurophysiological
      multi-channel data.
AB  - Progress in quantifying states of cerebral function and in the further
      development of automated EEG processing demands the application of suitable
      methods for the reduction of neurophysiological multi-channel data as well as
      their automatic classification. The method used here for reducing multi-channel
      data was to gain distributions of parametric descriptors from EEG data from
      computer-aided topographic electroencephalometry (CATEEM), for example the
      relative and absolute band power in the frequency bands delta, theta, alpha 1,
      alpha 2, beta 1, beta 2, total power, median and mode frequency, and other
      parameters. These values were subjected to cluster analysis. The classification
      of EEG parameters was carried out by means of discrimination analysis and neural
      networks. The practicability of both procedures was demonstrated in the reduction
      and classification of EEG data in the context of a normed study involving 104
      healthy adults. These data have been used as the basis for a new evaluation study
      of 60 additional intraoperative EEG recordings obtained with CATEEM. In that
      newly started study, the effects of sedative and anaesthetic drugs on EEG
      behavior and psychophysiologic behavior remain to be investigated.

PMID- 8738598
TI  - Automatic record keeping in anaesthesia--a nine-year Italian experience.
AB  - In 1986, in Buccheri La Ferla Hospital, Palermo, an anaesthesia information
      management project was started. Its aim was to develop a computerized anaesthesia
      workstation. Today, the system is in daily clinical use and has reached most of
      its original goals: Automatic collection of physiological signals and patient
      monitor trends is possible by means of analog-digital conversion or by using
      serial data transfer. A centralized display is included in the system to allow
      easy control of the progress of the anaesthetic procedures in the hospital.
      Available in the workstation, there is an on-line help function to assist
      pharmacological calculations and administration of anaesthesia drugs. Mail
      messages can be sent to different anaesthesia workstations and data can be shared
      between them. Information collected during preoperative visits is automatically
      transferred from a portable personal computer to the system. There is a nine-year
      patient data-base with both preoperative and perioperative anaesthesia
      information which can be accessed from each of the workstations. Today, the
      system is in daily routine use and comprises eight anaesthesia workstations and
      two portable personal computers used for preoperative visits. The operation
      schedule with anaesthetists' notes is printed both for surgical wards and for
      O.R., using information stored from preoperative visits to the system. For
      automated data collection a trend resolution of one minute has been used. The
      postoperative orders are printed from the system in the recovery room and given
      to the wards with the patient. The feedback from the seventeen anaesthetists and
      twenty-four nurses who use the system routinely is positive. Today, 16,000
      patient records are available in the database. This number increases by 3,300
      every year. With increasing computer utilization in patient treatment there have
      been no legal or administrative controversies. Based on nine years' experience,
      it is clear that the use of computers in anaesthesia practice improves quality of
      patient care.

PMID- 8738599
TI  - Safety factors in the remote control of infusion devices.
AB  - We have been using computer driven injections in surgery for many years to the
      benefit of more than thousand patients. Along these years we accumulated
      extensive experience in remote controlled infusion pumps. Today we have solved
      many communication problems. Despite the attention and care we brought in our
      software developments we still meet with some problems.

PMID- 8738600
TI  - Non-localizable alarm.

PMID- 8738601
TI  - Animal models of breast cancer: their diversity and role in biomedical research.
AB  - Animal models of breast cancer have been widely used to study various aspects of
      breast cancer biology, and are remarkably diverse, encompassing chemically and
      virally induced tumors, human tumor xenografts, and transgenic mouse models.
      Several novel models have become available during the past few years, including
      tumors induced by polyomavirus and adenovirus, and a series of human cell line
      variants. The several following articles describe, in some detail, the
      characteristics of these models and their relevance to the human disease.
      Descriptions of each of the major models, e.g., 7,12-dimethylbenz(a)anthracene
      induced, MMTV-associated, and human breast cancer cell line xenografts, also are
      included. The limitations and advantages of several of these models, and some
      issues relating to the choice of models, are briefly discussed in this overview.

PMID- 8738602
TI  - Experimentally induced mammary tumors in rats.
AB  - Among the multiple experimental animal models employed for analyzing the various
      aspects of mammary carcinogenesis, the induction of mammary tumors in rats by
      chemical carcinogens is one of the models most utilized. Experimentally-induced
      mammary tumors in rodents have proven to constitute useful tools for the study of
      the pathogenesis of cancer and of the molecular mechanisms involved in the
      initiation and progression of the neoplastic process. In vivo experimental animal
      models provide information not available in human populations; they are adequate
      for hazard identification, dose-response modeling, exposure assessment, and risk
      characterization, the four required steps for quantifying the estimated risk of
      cancer development associated with toxic chemical exposure. Using the DMBA rat
      mammary model, we have been able to demonstrate that the carcinogen acts on the
      intermediate cell of the terminal end bud (TEB), and that this structure is the
      one that evolves to intraductal proliferation, carcinoma in situ, and invasive
      carcinoma. There are several factors that regulate the susceptibility of the TEB;
      some of them are: a) topographic location of the mammary gland, b) age of the
      animal, and c) reproductive history. The understanding of the mechanisms that
      modulate tumorigenesis will further our knowledge and understanding in the
      prevention of the disease, as a result of the development of strategies for
      stopping the progression of the initiated cells.

PMID- 8738603
TI  - Experimental mammary epithelial morphogenesis in an in vivo model: evidence for
      distinct cellular progenitors of the ductal and lobular phenotype.
AB  - An in vivo transplantation system has been used to evaluate the developmental
      capacities of specific mouse mammary epithelial cell populations. Specifically,
      mouse mammary epithelial cells with distinctly limited developmental potentials
      have been identified using this procedure. Two distinct epithelial cell
      progenitors have been identified by experiments designed to determine whether
      basal lobular and ductal phenotypes could develop independently under conditions
      imposed by a limiting dilution. The prediction that these separate epithelial
      progenitors must exist was based upon the results from transplantation
      experiments carried out in epithelium-divested mammary fat pads of syngeneic mice
      with mammary epithelium from two different transgenic mouse models. The results
      presented here demonstrate the following points: 1) lobular, i.e. secretory,
      progenitor cells are present as distinct entities among the mammary epithelial
      cells found in immature virgin female mice; 2) similarly, ductal epithelial
      progenitors are present within the same population; 3) lobular progenitors are
      present in greater numbers, although both cell populations are extremely small;
      4) as expected, some inocula produce outgrowths with simultaneous development of
      both lobular and ductal phenotypes--it is not known whether this indicates
      cooperative interaction between the two epithelial progenitors or signals the
      presence of a third progenitor type capable of producing both ductular and
      lobular committed daughters; 5) these findings have important consequences in the
      design of experiments aimed at testing the effects of known and putative mammary
      oncogenes and tumor suppressor genes, using techniques which include cellular
      transformation in vitro followed by in vivo cultivation and evaluation.

PMID- 8738604
TI  - MMTV-induced mutations in mouse mammary tumors: their potential relevance to
      human breast cancer.
AB  - In mouse mammary tumor virus (MMTV) infected mice, three identifiable stages of
      mammary tumorigenesis can be biologically defined: preneoplastic hyperplastic
      nodules, malignant tumor, and distant metastatic lesions (primarily in the lung).
      MMTV is a biological carcinogen which induces somatic mutations as consequence of
      its integration into the host cellular genome. Each stage of mammary
      tumorigenesis appears to result from the clonal outgrowth of cells containing
      additional integrated proviral MMTV genomes. This phenomenon has provided the
      basis for an approach to identify genes which, when affected, may contribute to
      progression through the different stages of mammary tumorigenesis. Eight
      different genes (Wnt1, Wnt3, Wnt10b, Fgf3, Fgf4, Fgf8, Int3, and Int6) have been
      shown to be genetically altered in multiple mammary tumors as a consequence of
      MMTV integration. Although the significance of the human homologs of these genes
      as targets for somatic mutation during human breast carcinogenesis is only now
      being explored, it is clear that this work has led to a new appreciation of the
      complexity of the genetic circuitry that is involved in the control of normal
      mammary gland growth and development. It seems likely that some of the mutations
      induced by MMTV, and the signaling pathways in which these target genes take
      part, will be relevant to the progression from preneoplastic lesions to distant
      metastasis in human breast cancer.

PMID- 8738605
TI  - Mammary tumors induced by polyomavirus.
AB  - The first known member of the Polyomavirus family, murine Polyomavirus (MPyV),
      was discovered because of its oncogenic properties. The genetic simplicity of
      MPyV (shared with all members of the Py family), the wide spectrum of tumors
      induced by MPyV, and the convenient properties of its natural host, the mouse,
      make it a particularly interesting model system to study oncogenesis. This paper
      briefly reviews the virus infectious cycle and our current understanding of the
      viral proteins that are involved in oncogenesis, and focuses on recent studies on
      oncogenesis of the mammary gland. Mammary gland ductal adenocarcinomas develop at
      high frequency and with short latency in infected immunoincompetent adult female
      or normal neonatal mice or in transgenic mice expressing the viral oncogene,
      middle T. These tumors provide excellent model systems for the study of human
      breast cancer.

PMID- 8738606
TI  - Mammary tumors induced by human adenovirus type 9: a role for the viral early
      region 4 gene.
AB  - Human adenovirus type 9 (Ad9) elicits exclusively estrogen-dependent mammary
      tumors when injected into female rats. Three different histological types of
      mammary tumor (benign fibroadenomas, phyllodes tumors, and malignant solid
      sarcomas) have been described in Ad9-infected animals, with benign fibroadenomas
      being seen most frequently. Interestingly, in contrast to other adenoviruses, in
      which oncogenic viral functions are entirely encoded within the E1 region, Ad9
      requires an E4 region transforming protein (ORF1) for its unique mammary
      oncogenicity. Studies of Ad9-induced rat mammary tumors may lead to a detailed
      molecular understanding for the development of fibroadenoma, a common human
      breast tumor.

PMID- 8738608
TI  - The T61 human breast cancer xenograft: an experimental model of estrogen therapy
      of breast cancer.
AB  - Endocrine therapy is one of the principal treatment modalities of breast cancer,
      both in an adjuvant setting and in advanced disease. The T61 breast cancer
      xenograft described here provides an experimental model of the effects of
      estrogen treatment at a molecular level. T61 is an estrogen receptor positive
      tumor which was originally derived from a T1N0M0 invasive ductal cancer and has
      been carried as a serially transplanted xenograft in nude mice. T61 is a hormone
      sensitive tumor whose growth is suppressed by both estrogen and tamoxifen, in
      contrast to other estrogen receptor positive tumors such as MCF-7 which are
      stimulated by estrogen. Molecular studies have demonstrated that T61 expresses
      easily detectable levels of mRNA for a number of peptide growth factors,
      including transforming growth factor alpha (TGF-alpha) and insulin-like growth
      factors I and II (IGF-I and IGF-II), but not transforming growth factor beta-I
      (TGF-beta1). Of these, IGF-II is the only peptide whose expression is altered by
      endocrine therapy. Treatment of T61-bearing nude mice with physiologic doses of
      estrogen is accompanied by loss of IGF-II mRNA expression within 24 hours, and
      rapid regression of tumor. T61 tumor growth is also inhibited in animals treated
      with a monoclonal antibody which blocks binding of ligand to the IGF-I receptor,
      which mediates the mitogenic signal of bound IGF-II through autophosphorylation
      of its intracellular tyrosine kinase domain. These results demonstrate the
      utility of the T61 model in the study of the molecular mechanism of estrogen
      therapy in breast cancer, and suggest that in this system, modulation of a
      specific growth factor (IGF-II) by endocrine therapy can have profound effects on
      tumor growth.

PMID- 8738607
TI  - Human breast cancer cell line xenografts as models of breast cancer. The
      immunobiologies of recipient mice and the characteristics of several tumorigenic
      cell lines.
AB  - The ability to maintain and study human tissues in an in vivo environment has
      proved to be a valuable tool in breast cancer research for several decades. The
      most widely studied tissues have been xenografts of established human breast
      cancer cell lines into athymic nude mice. Human breast tumor xenografts provide
      the opportunity to study various important interactions between the tumor and
      host tissues, including endocrinologic, immunologic, and tumor-stroma
      interactions. The nude mouse is not the only immune-deficient recipient system in
      which to study xenografts. Additional single and combined mutant strains have
      been used successfully, including mice homozygous for the severe combined immune
      deficiency mutation (scid), both the beige (bg) and nude (nu) mutations in
      combination (bg/nu), and mice bearing the combined bg/nu/xid mutations. The
      differing immunobiologies are discussed, with particular reference to the
      immunobiology of breast cancer, as are the characteristics of several of the more
      frequently utilized breast cancer xenografts and cell lines. The ability of
      several endocrine treatments to modulate effectors of cell mediated immunity,
      e.g., estrogens and antiestrogens, and the effect of site of inoculation on tumor
      take and metastasis, also are described.

PMID- 8738609
TI  - Metastasis from human breast cancer cell lines.
AB  - Immunodeficient animals, principally nude mice, when used in appropriately
      designed studies have been shown to be useful for the experimental analysis of
      human breast cancer metastasis. As with many other human tumors, the implantation
      of breast cancer cells into an anatomically appropriate tissue (the mammary
      fatpad) results in increased tumor take and incidence of metastasis for certain
      cell lines compared with subcutaneous injection. Testing a number of widely
      available human breast cancer cell lines identified the MDA-MB-435 cell line as
      the most metastatic, producing lung and lymph node metastases in a high
      proportion of nude and severe combined immunodeficient (SCID) mice after
      injection in the mammary fatpad. Mixing human breast cancer cells with normal
      fibroblasts or with Matrigel also increases the tumor incidence and growth rates
      in nude mice. Different routes of injection can be used to assess the ability of
      human breast cancer cells to form metastatic lesions in the lungs (i.v.
      injection), the liver (injection in the spleen), the brain (direct or
      intracarotid artery injection) and the bone marrow and bone (injection into the
      left ventricle of the heart). These different approaches demonstrate the
      potential of experimental studies of human breast cancer growth and metastasis
      using immunodeficient mice; this model is valuable for experiments that test the
      role of metastasis-associated genes and the efficacy of novel forms of therapy.

PMID- 8738610
TI  - Fibroblast growth factor overexpressing breast carcinoma cells as models of
      angiogenesis and metastasis.
AB  - Progression of breast cancer from an estrogen-dependent, slowly growing tumor
      amenable to tamoxifen treatment to an aggressive, metastatic, estrogen
      independent phenotype has been mimicked by the transfection of MCF-7 breast
      carcinoma cells with fibroblast growth factors 1 or 4. FGF-transfected cells are
      aggressively tumorigenic in ovariectomized or tamoxifen-treated nude mice,
      conditions under which the parental cells would not produce tumors. When
      detection of metastasis was enhanced by lacZ transfection, the FGF-transfected
      MCF-7 cells were reliably metastatic to lymph nodes and frequently metastatic to
      lungs, in further contrast to parental cells. An antiangiogenic drug, AGM-1470,
      given to mice bearing tumors produced by FGF-transfected MCF-7 cells, produced a
      decrease in tumor size. The decreased tumor size was not as marked as that
      produced by treatment with pentosan polysulfate, an agent which would abrogate
      all autocrine or paracrine effects of the transfected FGF. Thus, increased
      angiogenesis may be a component of the phenotypic change produced by the FGF
      transfection, but other autocrine or paracrine effects may also be important.
      Since a clonal FGF-4 and lacZ doubly-transfected cell line, MKL-4, progressively
      lost expression of the transfected lacZ gene in individual cells, we performed
      successive rounds of fluorescence-activated cell sorting to select high
      expressing cells. High-expressing cell populations thus obtained rapidly lost
      expression of beta-gal activity in continued culture. High beta-gal expressing
      clonal cell lines of MKL-4 cells established by either one or two rounds of low
      density cloning also lost lacZ expression with continued culture. Southern
      analysis of DNA from lacZ transfected cell lines showed the transfected sequences
      to be present and grossly intact in both high and low expressing populations.
      However, Northern analysis revealed that high-expressing populations of MKL-4
      cells contained the most lacZ mRNA, implying that in the unstable MKL-4 cell
      line, individual cells are down-regulating mRNA levels of lacZ. Stable lacZ
      expression has been obtained in other FGF-transfected and parental MCF-7 cell
      lines using the same expression vector. Thus, the MKL-4 cell line is down
      regulating mRNA encoding the transfected gene through a mechanism not dependent
      on the CMV promotor utilized in the expression vector. This evidence suggests
      that lacZ expression is not a benign modification in certain cells.

PMID- 8738612
TI  - Urographic percentile charts for vertical kidney mobility in childhood.
AB  - Vertical kidney mobility was measured in excretory urograms in 492 children of
      both sexes, 1 to 16 years of age. The positions of the lower poles of the kidneys
      were compared in radiographs taken in recumbent and erect children. The mean
      values and standard deviations of the mobility were calculated (in mm) in 15 one
      year-age subgroups, body weight subgroups (intersubgroup difference = 5 kg) and
      in the lumbar segment L1-L4 length subgroups (intersubgroup difference = 5 mm),
      establishing the limiting values including 3, 10, 25, 50, 75, 90 and 97% of the
      studied population of boys and girls. It was found that in the group aged 15-16
      years, the mobility of the right kidney was greater than that of the left kidney
      both in boys and girls. With increasing body weight the mobility of both kidneys
      corresponding to the 97th centile increased in boys, while in girls the mobility
      of the right kidney decreased when the body weight of 60-70 kg was reached, and
      that of the left kidney decreased after reaching 50-60 kg. In boys with the
      increase in length of the lumbar segment L1-L4, the mobility values corresponding
      to the 97th centile were markedly increased. The obtained percentile charts of
      vertical kidney mobility in children will be useful when nephropexy is to be
      performed.

PMID- 8738613
TI  - Phaeochromocytoma in pregnancy: a case report.
AB  - A twenty-eight years old patient with phaeochromocytoma in pregnancy is reported.
      In the second trimester, she was admitted to hospital for complaints of headache,
      fever, palpitation and weakness. A phaeochromocytoma was diagnosed. Alpha and
      beta blockers were given to regulate arterial blood pressure until foetal
      maturity was reached. Delivery was by caesarean section and the operation was
      continued with a right adrenalectomy. Pathological examination revealed a
      phaeochromocytoma.

PMID- 8738614
TI  - Spontaneous fracture of indwelling ureteral stents in patients treated with
      extracorporeal shock wave lithotripsy: two case reports.
AB  - Placement of indwelling ureteral stents adjunctive to ESWL treatment has been a
      widespread practice. We herein present two cases of spontaneous breakage of
      double pigtail ureteral stents and their management. Prevention of this
      complication may be possible by careful examination of the stents prior to
      insertion, by following the instructions of manufacturers on maximum time limits
      and by using stent logs to keep track of patients.

PMID- 8738611
TI  - Transgenic mouse models of breast cancer.
AB  - Although valuable initial information can be gathered about transformation from
      in vitro studies, human cancer occurs in the context of a complex interaction
      with its environment and must ultimately be studied in living animals. Transgenic
      animal models have been used to study breast transformation for a number of years
      and have yielded valuable information on the subject. In this paper, we will
      summarize results from our laboratories, and others, regarding the use of
      transgenic mice to study breast tumorigenesis. We will also suggest future
      directions for the use of transgenic models to understand, and hopefully, one day
      to cure the disease.

PMID- 8738615
TI  - Retroperitoneal cystic lymphangioma diagnosed by computerized tomography,
      magnetic resonance imaging and thin needle aspiration.
AB  - We report a case of retroperitoneal cystic lymphangioma presenting with right
      pack pain. Although preoperative diagnosis is usually difficult in such a rare
      condition, we could make the preoperative diagnosis on grounds of the peculiar
      findings obtained by computerized tomography (CT), magnetic resonance imaging
      (MRI) and needle aspiration.

PMID- 8738616
TI  - A case in favour of one sided microscopic vasovasostomy--the New Delhi
      experience.
AB  - Between January 1987 and December 1991 we performed vasovasal anastomosis in 60
      patients who had undergone vasectomy for family planning. Of these, 30 patients
      were randomized for microscopic vasovasostomy and the remaining 30 patients had a
      macroscopic vasovasal anastomosis. Without exception the procedures were
      performed on one side only. Out of the 50 patients who reported for follow-up, 44
      had return of spermatozoa upon semen analysis. Pregnancy resulted in 30 out of 40
      patients who attempted conception (average 75%). There was one complication but
      no case of surgical trauma- or anaesthesia-related mishap was encountered. The
      results of the micro and the macro groups are analysed separately in order to
      draw conclusions.

PMID- 8738617
TI  - Carcinoma in situ and treatment options.
AB  - Carcinoma in situ (CIS) is a high-grade and aggressive manifestation of
      transitional-cell carcinoma of the bladder that has a highly variable course. The
      treatment of CIS has undergone dramatic changes since this malignancy was first
      recognized. While cystectomy was once recommended as the initial treatment of
      choice, recognition of the highly variable prognosis and the uniformly high
      response rate to intravesical BCG has prompted a more conservative approach to
      management. Patients who fail BCG immunotherapy without evidence of progression
      may yet be candidates for intravesical chemotherapy, photodynamic therapy, or
      alternative immunotherapies such as alpha-2b interferon, bromopirimine, or
      keyhole limpet haemocyanin.

PMID- 8738618
TI  - The effects of thiotepa, mitomycin C, BCG and interferon instillation on
      urothelium.
AB  - The effects of Thiotepa, Mitomycin C, BCG and Interferon on urothelium were
      researched in rabbits. Early changes of a contracted bladder such as fibroblastic
      atypia and sub-epithelial plaque were seen in all groups in different rates. This
      rate in the Thiotepa and BCG groups was 100% and in the Mitomycin C and
      Interferon groups 60%. There was no urothelial dysplasia in the BCG and
      Interferon groups, whereas in the Thiotepa group 100% and in the Mitomycin C
      group 40% were seen. In conclusion, urothelial dysplasia or fibroblastic atypia
      in random biopsies were criteria to prevent further complications in intravesical
      therapies.

PMID- 8738620
TI  - Effect of obesity on prostatic hyperplasia: its relation to sex steroid levels.
AB  - In 68 men with benign prostatic hyperplasia, we evaluated the association between
      obesity and prostatic enlargement, as well as changes in serum levels of
      oestradiol, testosterone, dihydroepiandrosterone and dihydroepiandrosterone
      sulphate. Despite the larger adenomas, no increase in the symptom score for BPH
      was observed with increasing obesity. Average specimen weights increased with
      increasingly obesity and increasing host age from 46 to 80 g. We also found the
      serum oestradiol level significantly elevated in obese men who were 140% or over
      recommended weight compared to underweight men younger than 60 years (51.3 pg/ml
      versus 26.8 pg/ml, p < 0.01). This pattern was present in all age groups. These
      results indicate that obesity is a risk factor for prostatic enlargement but not
      for obstruction. Also the degree of obesity appears to have a direct effect on
      oestradiol levels through transformation of androgens in adipose tissue to
      oestrogens. In conclusion, further studies to evaluate the pathogenesis,
      pathophysiology, natural history and symptomatology of BPH would be of great
      interest and should help to define better the associations that we have
      recognized.

PMID- 8738619
TI  - Usefulness of Cernilton in the treatment of benign prostatic hyperplasia.
AB  - A total of 89 patients with benign prostatic hyperplasia (BPH) were treated
      pharmacologically for 4 months: 51 received Cernilton and 38 Tadenan (controls).
      Significant subjective improvement was found in 78% of the patients in the
      Cernilton group compared to only 55% of the Tadenan-treated patients. The
      obstructive and irritative symptoms responded best to the therapy. In the
      Cernilton-treated patients a significant improvement in the uroflow rate,
      decrease in residual urine and in prostate volume were found. This study shows
      that Cernilton is an effective therapy for patients with BPH.

PMID- 8738621
TI  - Norepinephrine contents of human prostatic hyperplasia: differences between
      pathological subtypes.
AB  - Tissue norepinephrine content in benign prostatic hyperplasia (BPH) was evaluated
      to detect possible histological differences in BPH subtypes and to investigate
      the correlation between norepinephrine levels and age, prostatic weight and
      clinical symptom score, respectively. Specimens were obtained from 28 patients
      who underwent transurethral resection of the prostate. Pathologically, 18 out of
      28 specimens were classified as fibromyoadenomatous hyperplasia and the remaining
      10 as fibromuscular type. Norepinephrine content in the fibromyoadenomatous type
      was 133.1 +/- 23.1 ng/g, whereas it was 340.3 +/- 60.5 ng/g in the fibromuscular
      type. Norepinephrine level in the former group was significantly lower than that
      in the latter group (p < 0.001). In both groups, there was no correlation between
      norepinephrine content, age and clinical symptom score, while the norepinephrine
      content had a reverse correlation with prostatic weight only in the former group
      (p < 0.05). In conclusion, norepinephrine levels were dependent upon histological
      differences, especially upon the amount of smooth muscle elements, in the
      evaluated specimen. Severity of prostatism and patients' age showed no
      correlation with tissue norepinephrine content.

PMID- 8738622
TI  - Prostatic acid phosphatase and prostate specific antigen in liver disease.
AB  - Serum concentrations of prostate specific antigen (PSA) and prostatic acid
      phosphatase (PAP) were measured in 51 liver cirrhosis, 37 chronic active
      hepatitis (CAH) patients and 26 healthy individuals. Elevated PSA levels have
      been found in 2 of cirrhotic patients while no increase has been detected in CAH
      and controls. Serum PAP levels have been observed slightly increased in 2
      patients with cirrhosis, 2 patients with CAH and 1 control case. Mean PSA and
      mean PAP values showed no significant difference between groups (p > 0.05). Serum
      PSA and PAP levels are reliable in diagnosing and monitoring prostate cancer in
      chronic liver patients and maintain their specificity in this situation.

PMID- 8738623
TI  - Intraobserver and interobserver reproducibility of WHO and Gleason histologic
      grading systems in prostatic adenocarcinomas.
AB  - In this study a total of 96 patients with prostatic carcinoma were evaluated
      retrospectively. Sections prepared from paraffin blocks were examined and all
      cases were scored according to the World Health Organization (WHO) and Gleason
      grading systems. We investigated intraobserver and interobserver reproducibility
      of two grading systems in prostatic adenocarcinomas. In our study the
      intraobserver reproducibilities of the WHO and Gleason systems were 75.0% and
      78.1%, respectively. The interobserver reproducibilities of the WHO and Gleason
      grading systems were 60.4% and 70.8%, respectively. While there was no difference
      between intraobserver and interobserver variations in the Gleason system (p >
      0.05), there was significant difference between intraobserver and interobserver
      variations in the WHO system (p < 0.05).

PMID- 8738624
TI  - Etoposide, epirubicin and carboplatin in hormone-refractory prostate cancer.
AB  - Twelve patients with hormone-refractory prostate cancer were treated with
      combination chemotherapy of etoposide, epirubicin and carboplatin (EEC). At
      relapse, all patients had metastases to the bone and/or soft tissues. The median
      number of courses was 3 (range 1-10). Epirubicin was not administered in 6
      patients because of heart disease. Three patients (25%) had a partial response
      and 8 (67%) showed no change. The overall response rate was 92%. Pain relief was
      observed in 4 patients (44%). Four patients were still alive after a mean
      observation period of 18 months (range 4-36 months), while 8 died with a mean
      survival period of 11 months (range 7-15 months). Nausea, appetite loss, and
      alopecia were observed in some patients. All except one patient experienced bone
      marrow suppression, 5 of whom were treated with granulocyte-colony stimulating
      factor. EEC chemotherapy in hormone-refractory prostate cancer is considered to
      be more effective than other kinds of chemotherapy, whereas it frequently induces
      bone marrow suppression.

PMID- 8738625
TI  - Perineal prostatic cancer seeding following Urocut needle biopsy.
AB  - A case of perineal tumour seeding after needle core biopsy of prostatic cancer is
      presented. This rare complication of prostatic needle biopsy occurred following
      false-negative tissue sampling in a patient subsequently treated by irradiation
      therapy and total androgenic blockade.

PMID- 8738626
TI  - Laparoscopic varicocele ligation.
AB  - Varicocele, an abnormal dilatation of the pampiniform plexus, frequently
      contributes to male factor infertility. We performed laparoscopic varicocelectomy
      in 20 patients with varicoceles and abnormal seminal findings. The spermatic
      artery was identified and preserved in 13 patients and was clipped along with the
      veins in 7 patients including 1 patient with bilateral varicocele. The time
      required for the artery-ligating surgery ranged from 90 to 120 minutes with an
      average of 113.2 minutes, while the time needed for the artery-preserving
      technique ranged from 90 to 250 minutes with an average of 158.0 minutes. Some
      analgesics were administered to 11 patients, while the other 9 patients needed no
      analgesics. All patients were able to walk within 24 hours of the operation. The
      mean hospitalization period after the operation was 5.9 days. Sperm
      concentrations significantly improved postoperatively (p < 0.05). No difference
      in postoperative improvement of seminal findings was observed between artery
      ligating and artery-preserving groups. A slight scrotal emphysema developed
      during the operation in 1 patient. Abdominal pain was experienced in 1 patient,
      but subsided within a few days. No serious complications were observed. The
      laparoscopic technique may replace routine open high ligation as the surgical
      treatment of choice, especially in patients with bilateral varicocele.

PMID- 8738627
TI  - Chromosomal anomalies in cryptorchidism.
AB  - Chromosome analysis was performed in 160 patients with cryptorchidism.
      Chromosomal anomalies were found in 7 patients (4.4%). The incidence of
      chromosomal abnormalities was not significantly different between patients with
      bilateral or unilateral cryptorchidism. Of 7 patients, 1 had sex chromosomal
      aberration, 2 had marker chromosome and 4 had autosomal anomalies. Additional
      congenital anomalies were observed in 1 with sex chromosomal aberration, 2 with
      marker chromosome and 2 with autosomal anomaly. These facts indicate that we had
      better perform chromosome analysis in all patients with bilateral or unilateral
      cryptorchidism.

PMID- 8738628
TI  - Cryptorchidism, micropenis and clinical anophthalmia epilepsy in a retarded boy.
AB  - A boy was found to have bilateral anophthalmia at birth. General health
      examination revealed cryptorchidism and micropenis. Physical and mental
      retardation in addition to epilepsy were observed. Karyotype showed 47, XY. No
      report has ever described such a case of dysmorphic syndrome.

PMID- 8738629
TI  - A malignant mixed gonadal stromal tumour of the testis with heterologous
      components.
AB  - We report a case of malignant mixed gonadal stromal tumour in the testis, which
      consisted of epithelial heterologous components and metastasized to the
      retroperitoneal lymph nodes. The primary lesion and biopsy of the retroperitoneal
      metastases showed predominance of the Sertoli cell component. The patient was put
      on chemotherapy.

PMID- 8738630
TI  - Failure of artificial insemination of husband's semen in the treatment of male
      infertility.
AB  - In the management of infertility, in case semen quality is found insufficient and
      could not be improved by medical means, handling the available spermatozoa in the
      most beneficial way has been aimed. Thus, artificial insemination with low
      quality semen has become a therapeutic alternative. In this study homologous
      artificial insemination has been used to treat infertility caused by
      oligoasthenospermia. Eighteen couples have been treated for 58 cycles by
      intrauterine or paracervical insemination using cervical cups. During the same
      period 42 cycles with timed vaginal intercourse have been assessed. Though no
      pregnancies could be obtained following artificial insemination, one pregnancy
      occurred during no-treatment cycles.

PMID- 8738632
TI  - Loudness ratio production by cochlear implantees using the spectral maxima sound
      processor.
AB  - The loudness growth characteristics of five users of the Mini System 22 implant
      and the Spectral Maxima Sound Processor were measured and compared with those of
      five normally hearing subjects. The main objective was to evaluate the
      suitability of the function employed in the sound processor that converts
      acoustic input levels of electrical stimulation. The method of loudness ratio
      production was used. The average result of the normally hearing subjects for
      halving and doubling loudness was 10.8 dB. The results of three of the implantees
      were comparable with those of the normally hearing subjects (average 8.83 dB),
      while those of the remaining subjects were quantitatively and qualitatively
      different. Investigation showed that altering the amplitude conversion function
      in the sound processor would not make the results of these two implantees more
      like those of the other subjects. However, it is possible that their responses
      were affected by the limited input dynamic range of the sound processor.

PMID- 8738631
TI  - Inhibition of glucose uptake by 5-hydroxyindoleacetic acid in the isolated rat
      soleus muscle.
AB  - Accumulated end-products were identified to participate in the late development
      of glucose intolerance and insulin resistance (IR) in patients with chronic renal
      insufficiency. The possible pathophysiological role of accumulated 5-hydroxy
      indoleacetic acid (5HIAA) in the genesis of IR was investigated employing an in
      vitro animal model. 5HIAA inhibited the basal glucose uptake in isolated rat
      soleus muscle with intact membrane with A50 = 1.25 mumol/l, and Emax = 88.6%.
      5HIAA significantly inhibited the insulin, and tolbutamide stimulated glucose
      uptake. In Ca and Mg depletion 5HIAA showed a partially additive inhibitory
      effect, while nonadditive inhibitory activity was observed in the case of K+
      excess. It is concluded that 5HIAA is a metabolically active end-product
      interfering with glucose uptake in muscle at an insulin postreceptor level, and
      its effect is related to Ca modulation in the insulin regulatory cascade.

PMID- 8738633
TI  - Determinants of speech-hearing disability in King-Kopetzky syndrome.
AB  - King-Kopetzky syndrome is characterized by auditory disability with a clinically
      normal hearing threshold. The main reported disability is hearing speech in the
      presence of background noise. The degrees of speech-hearing disability in
      patients with King-Kopetzky syndrome have been investigated with the use of the
      Social Hearing Handicap Index (SHHI), and the relationships between the SHHI
      scores and a number of physiological, psychoacoustical and psychological factors
      determined in 109 patients. The significantly higher (worse) SHHI scores in
      patients with King-Kopetzky syndrome indicate that this group suffer a
      considerable degree of speech-hearing disability. In our study, the main findings
      are that some psychological factors, performance of the sentence in noise test
      and auditory thresholds are significantly correlated with the SHHI scores. We
      were unable to find any relationships between the SHHI and frequency resolution
      or EOAEs. In a multiple stepwise regression, somatic anxiety and the performance
      of the sentence in noise test are the significant predictors of SHHI scores.
      These two variables appear to be the main determinants of speech-hearing
      disability in King-Kopetzky syndrome.

PMID- 8738634
TI  - Facial expressions and speechreading performance.
AB  - In the present study, the role of facial expressions in visual speechreading
      (lipreading) was examined. Speechreading was assessed by three different tests:
      sentence-based speechreading, word-decoding, and word discrimination. Twenty
      seven individuals participated as subjects in the study. The results revealed
      that no general improvement as a function of expression was obtained across all
      tests. Nevertheless, skilled speechreaders could significantly improve their
      performance as a function of emotional expression in the word-decoding and word
      discrimination conditions. Furthermore, a correlational analysis indicated that
      there was a significant relationship between the subjects' rating of confidence
      regarding their responses to each test-item and performance on speechreading
      tests where lexical analysis is a necessary task-demand. The results are
      discussed with respect to how information from facial expressions is integrated
      with the information given by the lip movements in visual speechreading, and also
      with respect to general models of face-processing (i.e., Bruce & Young, 1986;
      Young & Bruce, 1991).

PMID- 8738635
TI  - Evaluation of the list of numerals in the Danish speech audiometry material.
      Dantale.
AB  - The psychometric function for the list of numerals in the Danish 'Dantale' speech
      audiometry material was obtained by presenting the lists to 30 normally hearing
      subjects at eight different sound pressure levels. Six of the subjects
      participated in a test of a possible learning effect. The psychometric function
      is presented, showing that 50% speech recognition is reached at a mean of 15 dB
      SPL, and the slope of the function around the 50% value is 8.3% per dB. It was
      found that in no more than 7% of the cases was each numeral on the list confused
      with another numeral. A strong correlation between the recorded RMS value and the
      SRT for the individual numeral was found. The short-term learning effect was
      found to be negligible.

PMID- 8738636
TI  - Auditory brainstem response. A comparison of different interpretation strategies
      for detection of cerebellopontine angle tumors.
AB  - In this retrospective study (111 tumor; 1370 non-tumor patients), the
      effectiveness of the auditory brainstem response for identifying cerebellopontine
      angle tumors was studied using different criteria to interpret the test.
      Individual ABR features were examined. The I-V was best (sensitivity = 82%;
      specificity = 97%) but present for only 44% of the population; I-III (sensitivity
      = 50%; specificity = 96%) and III-V (sensitivity = 30%; specificity = 97%) were
      worst. Ninety-three percent of patients had V and ILDV, with good results
      (sensitivity = 74% and 81% respectively; specificity = 93% each). Three
      interpretation strategies were compared: (1) included the latencies of V, ILDV, I
      V, III-V and I-III and ILDI-V, (2) excluded III-V and I-III, (3) used I-V and
      ILDI-V when available; V and ILDV otherwise. When corrected for hearing loss,
      strategy 3 provided significantly better specificity (91%) than strategy 1 (87%),
      with no significant difference in sensitivity (92% and 93%, respectively).

PMID- 8738637
TI  - Hearing disability assessment in evaluating hearing aid benefit.
AB  - The aim was to study the applicability of an eight-item questionnaire in
      evaluating the benefit derived from hearing-aid use. Since 1977, 3402 hard-of
      hearing patients have been fitted with a hearing aid for the first time and
      followed up for 3 months in the Helsinki University Central Hospital. The
      questionnaire included eight situation-specific items in hearing: speech face-to
      face, speech in a small and large group, loud speech, in telephone and radio/TV,
      doorbell, telephone signal. The scoring ranged from 0 to 16. After a 3 months'
      use of amplification, the questionnaire was completed again. The median
      (interquartile range) and arithmetic mean (standard deviation) of the prefitting
      scores were 5.0 (4.0-6.0) and 5.3 (2.33). The postfitting scores were 1.0 (0.0
      2.0) and 1.1 (1.17), respectively. The difference was highly significant. An
      eight-item questionnaire in the evaluation of hearing problems provided a
      reliable numerical score of disability. Follow-up is important to secure
      satisfactory results in rehabilitation, especially in old age.

PMID- 8738638
TI  - Lipreading with auditory low-frequency information. Contextual constraints.
AB  - The present experimental study investigated potential relations among three
      variables: (1) an audiovisual speech signal (i.e., low-frequency supplemented
      lipreading as opposed to pure lipreading), (2) typical, as opposed to atypical,
      sentences in a particular script (e.g., in a restaurant), and (3) the
      presence/absence of additional context (in the particular script) in 60 normal
      hearing subjects. All three variables revealed significant main effects, but no
      interactions were observed. The general facilitatory effect for the audiovisual
      signal is in line with previous research, but this effect was relatively weak
      compared to the main effect of typicality, which relies on cognitive activation
      of scripts. In a separate analysis, the typicality variable was also the only
      variable that interacted significantly with speechreading skill, typical
      sentences being perceived relatively easier by the skilled as opposed to the less
      skilled individual. The clinical implications of cognitive factors in hearing-aid
      fitting procedures, the construction of speech materials, and selection of
      individuals for rehabilitation were discussed.

PMID- 8738639
TI  - Auditory deficits and hearing loss associated with focal brainstem haemorrhage.
AB  - Four cases of central pontine haemorrhage are described in which auditory
      dysfunction was documented. Two cases had a hearing loss, in one of which there
      was recovery of the low frequencies. This case provides support for the tonotopic
      organization of the auditory pathways in the caudal pontine area, with the lowest
      frequencies being encoded medially. In all cases, there were abnormalities of the
      auditory brainstem responses, wave V being consistently involved, while wave III
      was abnormal in only one patient. In three cases, the masking level differences
      and crossed acoustic reflex thresholds were abnormal. The ipsilateral reflex
      thresholds were normal at least on one side in all cases. In the patient with the
      most significant hearing loss, loudness recruitment, assessed both
      psychophysically and with the acoustic reflex thresholds, was evident. These data
      are interpreted in terms of there being damage to the medial superior olivary
      nuclei and trapezoid body involving both afferent and efferent fibres.

PMID- 8738640
TI  - What is a psychosocial approach to hearing loss?
AB  - A psychosocial approach to hearing loss spans individual, contextual, and
      historical circumstances affecting the experience of impaired hearing.
      Assumptions about hearing impairment and its remediation are considered, and
      emphasis is given to the features that promote the undesirability of the status
      of being hearing impaired. Two current models for rehabilitation are noted; their
      assumptions are discussed in the light of both the preceding analysis and of
      empirical findings which suggest attention needs to be focused on individual
      issues.

PMID- 8738641
TI  - The stigma attached to hearing impairment.
AB  - Detailed analyses of the experience of impaired hearing demonstrate the ways in
      which it represents a threat to social identity. The reluctance to acknowledge
      impairment stems from the negative consequences of disclosing that status. The
      stigma attaching to hearing loss can be understood in the broader conceptual
      framework of 'shaming'. Generating stigma also needs to be understood at the
      micro-(interpersonal) and macro-(social) levels. The significance of stigmatizing
      in relation to rehabilitative strategies allows a reorientation to the issue of
      "normalisation' of identity, alongside treatment of disability.

PMID- 8738642
TI  - Occupational hearing loss: coping and family life.
AB  - Too many individuals still unnecessarily develop noise-induced hearing loss
      (NIHL). Interviews with men with NIHL showed their lack of awareness of noise as
      a threat to hearing. Also, most men were unwilling to acknowledge, or even
      denied, their hearing problems. Interviews with spouses of men with NIHL showed
      that the husband's hearing loss often caused misunderstandings and irritation
      within the family, which had a negative impact on the couple's intimate
      relationship. The purposes of our group rehabilitation programme, designed for
      men with NIHL and their spouses, were to give psychosocial support, adequate
      information and practice in effective coping strategies. A professional approach
      to treat men with NIHL is to take a patient-centered global perspective, which
      encourages the patient to identify, describe and acknowledge problems related to
      his impaired hearing. In the next step, the patient needs professional help to
      solve experienced hearing related problems. In this process of identification of
      and solution to problems, family involvement is important and vital.

PMID- 8738643
TI  - The subjective meaning of illness in severe otosclerosis: a descriptive study in
      three steps based on focus group interviews and written questionnaire.
AB  - The aim of this study of otosclerosis patients was to highlight the circumstances
      specific to an operable middle ear disease and to describe the psychologically
      unique aspects accompanying this disorder. In a first step five subjects
      participated in four focus group interviews, from which emanated a questionnaire
      answered in a second step by 28 randomly chosen subjects. Finally a second series
      of supplementary focus interviews were conducted with another group of subjects,
      after which the interview material was subjected to code-mapping, agreement and
      validation. The study results indicate that ear surgery was a very important
      occurrence in the lives of the patients and a unique aspect was that they were
      burdened by a sense of responsibility for deciding in favour of or against the
      ear surgery and in choosing the time for operation. An event as tangible as an
      operation impacts on the individual's psychological processing of the fact that
      one of his or her senses is damaged. The message to the person's surroundings is
      very clear: the operation makes others understand how serious the situation is,
      gives rise to a sense of sympathy. These factors together may promote adaptation
      to the handicap, or alternately, at least for some persons, may impede adaptation
      to the necessary hearing aids. To some individuals hearing aids were strongly
      associated with periods of deteriorating hearing and therefore had negative
      connotations. Thus the hearing aid was used while waiting for surgery or instead
      of surgery. The constant hope of regaining one's hearing through ear surgery,
      although not totally realistic in these cases of severe otosclerosis, always
      makes the hearing aid the second best solution. The overall conclusion from this
      study is that there are specific circumstances of an operable ear disease which
      have great impact upon quality of life, well-being and adaptation. The
      psychological situation is one of instability, feelings of responsibility and at
      times of anxiety. Patients with otosclerosis are sometimes told that they are
      better off than others with impaired hearing, because surgery can improve their
      hearing and because good amplification through hearing aids can be achieved in
      persons with conductive hearing losses. It is our hope that this study has helped
      to provide a fuller picture of the facts of life for persons with severe
      otosclerosis.

PMID- 8738644
TI  - Meniere's disease: trauma, distress and adaptation studied through focus
      interview analyses.
AB  - In order to investigate, in depth, the role of psychological factors in Meniere's
      disease, i.e. how the patients experience and interpret their symptoms during the
      process of this illness, a qualitative method "focus group interviews" was used
      as a study design. The focus group included four subjects; one woman and three
      men. In addition, semi-structured interviews were performed with each of four
      more subjects having the disease, three women and one man, in order to guarantee
      representativity in terms of gender and age. Through the focus interview analyses
      eight final codes and a number of sub-codes were developed. Results clearly
      pointed out the significance of the first traumatic attack of the disease as well
      as early signs; different "psychosomatic" symptoms prior to the attacks. The
      recognition of fear and phobic reactions in the manifestation of the vertigo
      attack was considered as an important observation, as attacks often were
      triggered by distressing thoughts as well as by sensory sensations. Other areas,
      touched upon for future investigation, were crisis adaptation and illness
      function.

PMID- 8738645
TI  - Hearing rehabilitation in a psychosocial framework.
AB  - This paper is primarily concerned with handicap, which emphasises the
      psychosocial consequence of hearing loss, its development and a framework for its
      alleviation. The development of handicap is considered, taking as a starting
      point the World Health Organization Definitions of disablements and their
      application to audiology by Stephens and Hetu (1991). This is extended in the
      light of recent work on the role of significant others and of positive
      experiences arising from the hearing loss. This approach is then incorporated
      into an update of the Goldstein/Stephens (1981) management model of audiological
      rehabilitation which provides a framework applicable in any sociomedical
      situation.

PMID- 8738646
TI  - Conformationally restrained peptides: crystal structure of tert-butyloxycarbonyl
      L-alanyl-D-alanyl-D-aminosuccinyl-glycyl-L- alanine methyl ester.
AB  - The solid-state structure of a heterochiral peptide embodying a D-aminosuccinyl
      peptide (D-Asu) and a D-Ala was studied in order to analyse the effects of Asu
      and amino acids with inverse chirality on peptide conformation. The crystal
      structure has been determined by X-ray diffraction techniques and refined to a
      final R factor of 0.043. The molecule adopts an unusual overall "S-shape'
      conformation due to two consecutive type II beta-turns. In this molecule it is
      possible to compare a type II beta-bend conformation (L-Ala1-D-Ala2) favoured by
      the presence of a D-residue at second corner to a type II beta-turn (D-Asu3-Gly4)
      favoured by the presence of a D-Asu residue at first corner. In agreement with
      previous studies, this structure confirms that the Asu has a high propensity to
      adopt a type II or II' beta-bend conformation and that it may be used as a strong
      determinant of these structural motifs.

PMID- 8738647
TI  - Crystallographic characterization of geometry and conformation of TOAC, a
      nitroxide spin-labelled C alpha,alpha-disubstituted glycine, in simple
      derivatives and model peptides.
AB  - The molecular and crystal structures of one derivative and two oligopeptides of
      TOAC, a nitroxide spin-labelled C alpha, alpha-disubstituted glycine, have been
      determined by X-ray diffraction. The derivative is the 5(4H)-oxazolone from Piv
      TOAC-OH; the oligopeptides are Z-TOAC-(L-Ala)2-NHtBu sesquihydrate and pBrBz-TOAC
      (L-Ala)2-TOAC-L-Ala-NHtBu hemihydrate. Incipient and fully developed right-handed
      3(10)-helical conformations are formed by both independent molecules in the
      asymmetric unit of the terminally blocked tripeptide amide and the terminally
      blocked pentapeptide amide, respectively. The average geometry and preferred
      conformation for the piperidine ring of the TOAC residues are also discussed in
      detail.

PMID- 8738648
TI  - Monte-Carlo calculations of the solvent effects on the conformation of
      angiotensin II.
AB  - An efficient Metropolis Monte-Carlo (MMC) procedure is proposed in order to
      calculate averages of the energy of conformation and structural properties of a
      polypeptide chain in interaction with a solvent. The contribution of hydration to
      the free energy of conformation of the macromolecule is calculated using the
      accessible surface area method. This algorithm, performed with different sets of
      atomic solvation parameters (ASP), is applied to the peptidic hormone angiotensin
      II. Different situations of solvation of that molecule are described when the ASP
      of the polar atoms are fixed to 0, whereas those of the apolar atoms are given
      values varying from -1.0 to 1.0. From results thus obtained, transitions from
      extended to collapsed conformations of the polypeptide chain can be simulated.
      Such changes of conformation could be related to a possible mechanism of binding
      of this hormone on a membrane surface.

PMID- 8738649
TI  - Solid-phase synthesis of H- and methylphosphonopeptides.
AB  - We introduce solid-phase syntheses of H- and methylphosphonopeptides, giving
      access for the first time to a new class of mimics for o-phosphoamino acids. The
      model peptides H-GlyGlyXaaAla-OH (Xaa = Ser, Thr) were synthesized on a solid
      phase using Fmoc/tBu strategy and HBTU/HOBt activation by incorporation of
      hydroxyl-protected serine and threonine. As selectively cleavable hydroxyl
      protecting groups we used triphenylmethyl and tert-butyldimethylsilyl for both
      amino acids, as described in the literature. All peptides were phosphitilated
      with O, O-di-tert-butyl-N,N-diethylphosphoramidite and yielded H
      phosphonopeptides after trifluoroacetic acid cleavage. Alternatively we
      phosphonylated the peptides with O-tert-butyl-N,N-diethyl-P
      methylphosphonamidite, which was synthesized by a two-step one-pot procedure
      starting from commercially available chemicals. All H- and
      methylphosphonopeptides were obtained in high purities and yields, as shown by
      reversed-phase high-performance liquid chromatography and anion-exchange
      chromatography. The phosphonopeptides were characterized by 1H and 31P NMR. We
      confirmed their molecular masses by electrospray mass spectrometry and analyzed
      their fragmentation schemes, which seemed to be characteristic for each class of
      analogues. The H-phosphonopeptides lost phosphonic acid (H3PO3, 82 mass units)
      and the methylphosphonopeptides lost methylphosphonic acid (MeH2PO3, 96 mass
      units). Both H- and methylphosphonopeptides represent a new and simply accessible
      class of mimics for phosphopeptides. Compared with the corresponding
      phosphopeptides all phosphonopeptides were synthesized in higher yields and
      purities (> 80%).

PMID- 8738650
TI  - Physico-chemical characterization of legumin-T from faba bean (Vicia faba L).
AB  - Legumin-T, the high-molecular mass product of limited tryptic hydrolysis of faba
      bean legumin, was investigated using hydrodynamic methods, static light
      scattering, fluorescence and ultraviolet spectroscopy. The following physico
      chemical parameters were determined in a high-ionic strength buffer system:
      molecular mass, 2.4 x 10(5) g/mol; sedimentation coefficient, SO20 = 10.8 x 10(
      13)Si; diffusion coefficient, DO20 = 4.1 x 10(-7) cm2 s-1; intrinsic viscosity,
      [eta] = 3.51 mL/g; partial specific volume, v = 0.719 mL/g; frictional ratio,
      f/f0 = 1.22; shape factor, beta = 2.17 x 10(6). Conformational changes during the
      formation of legumin-T can be deduced from the fluorescence emission and UV
      spectra.

PMID- 8738651
TI  - Structural redesign and stabilization of the overlapping tandem beta-turns of RNA
      polymerase II.
AB  - Peptides representing single repeat units of the carboxy-terminal domain (CTD) of
      RNA polymerase II (Tyr-Ser-Pro-Thr-Ser-Pro-Ser-Tyr-NH2, 1) contain overlapping
      Ser-Pro-Xaa-Xaa beta-turn forming sites which permit their overall structure to
      closely resemble members of the quinoxaline class of antitumor DNA
      bisintercalators. We have modified this native sequence at the i+2 positions of
      each beta-turn unit by substituting Gly or D-Ala in an attempt to preorganize
      this structure in aqueous solution. CD and NMR spectroscopic investigations
      confirmed the presence of type II beta-turns within each of the substituted
      peptides in contrast to the native sequence which contains a relatively low
      population of turn structure. In addition, an examination of singly substituted
      peptides suggests that an increase in the population of beta-turn structure
      within the amino-terminal Ser-Pro-Xaa-Xaa site also increased the formation of
      beta-turn structure in the carboxy-terminal (unmodified) Ser-Pro-Xaa-Xaa site; in
      comparison, substitution in the carboxy-terminal site did not influence structure
      in the remaining portion of the peptide. Overall, these results suggest that the
      structures formed could provide unique, preorganized linkers for the construction
      of novel DNA-interactive bisintercalators.

PMID- 8738652
TI  - Peptide synthesis on chitin.
AB  - The use of chitin as a support for solid-phase peptide synthesis is described and
      illustrated by synthesis of four peptides, varying in length from 10 to 29
      residues. Syntheses were performed in a continuous-flow peptide synthesizer,
      using Fmoc chemistry. A cleavable linker, p-[(R,S)-alpha-[1-(9H-fluoren-9-yl)
      methoxyformamido]-2,4-di methoxybenzyl]- phenoxyacetic acid, was attached to
      chitosan at the desired substitution level, and the complex acetylated to yield a
      linker substituted chitin. The effects of temperature, solvents and degree of
      linker substitution on the syntheses were studied. Acyl carrier peptide (ACP)
      synthesis studies indicated that temperature was the single most important
      parameter. Increasing the temperature of the synthesis from 20 to 55 degrees C
      resulted in an enormous improvement of this synthesis, with about 90% of the
      crude product being the correct peptide. Denaturing solvents, such as DMSO, could
      be used without significant effect on the flow properties of the support. The
      synthesis of one peptide was mainly improved by lowering the degree of
      substitution from 0.3 to 0.1 mmol/g, suggesting peptide aggregation was a problem
      in this case. The results of three syntheses on chitin were comparable with those
      obtained with a commonly used commercial support. This work shows that, under
      appropriate conditions, chitin can be utilized directly as a support for peptide
      synthesis.

PMID- 8738653
TI  - Phosphoryl transfer reaction regulated by amino acid side chains: a model for
      phosphoproteins.
AB  - Through a kinetic study of the reaction of phosphoamino acids as incubated in
      alcohol, it was found that the inter- and intramolecular phosphoryl transfer
      reactions were regiospecific and stereoselective. First, the phosphoryl transfer
      reaction required the regio-specifically neighboring alpha-carboxy group
      activation of amino acid but not beta-carboxy group. The intramolecular side
      chain catalytic effects relative to hydrogen for N-phosphoamino acids compared to
      N-phosphoglycine were a 119-to 4-times enhancement of the phosphoryl transfer
      reaction, respectively. Secondly, the intramolecular N-->O phosphoryl transfer
      migration was highly stereoselective, since the reaction rate constant of
      phosphoallothreonine relative to its diastereomeric threonine was reduced to
      half. The pentacoordinate transition states modulated by the amino acid side
      chains were demonstrated by the formation rates of intramolecular pentacoordinate
      spiro mixed anhydride compounds.

PMID- 8738654
TI  - Solution structure of the phosphorylated sites of ribosomal protein S6 by 1H NMR
      spectroscopy.
AB  - An increase in the rate of protein synthesis is found to be accompanied by
      phosphorylation of the 40S ribosomal protein S6. Treatment of S6 by cyanogen
      bromide produced three fragments, and one of the fragments of S6, which is a C
      terminal portion of S6 (M(r) approximately 4,000), contains all phosphorylation
      sites of S6. The C-terminal fragment of S6 contains seven serines. S6 kinase
      phosphorylates S6 specifically, i.e. five serines in the C-terminal of S6 are
      phosphorylated. The three-dimensional structure of S6 peptide was studied in 50%
      trifluoroethanol/50% H2O solution by 1H NMR with combined use of distance
      geometry and restrained molecular dynamics calculations. NMR results indicated
      that it takes an alpha-helix between Glu5 and Arg21 and a distorted helical
      structure for the following three residues, but no rigid structure was present
      from Ser25 through the C-terminus and for the N-terminal region (Lys1-Lys4). The
      specificity of the phosphorylation of the peptide is discussed from a structural
      aspect.

PMID- 8738655
TI  - The effects of aspartic acid-bond isomerization on in vitro properties of the
      amyloid beta-peptide as modeled with N-terminal decapeptide fragments.
AB  - The 42-amino acid A beta, the major constituent of the senile plaque deposits of
      the brains of Alzheimer's disease patients, exhibits a high degree of
      heterogeneity at its N-terminus. Isomerization of aspartic acid bonds at residues
      1 and 7 renders A beta more prone to aggregate and form extended structure as it
      was shown by in vivo and in vitro studies. We recently demonstrated the ability
      of mid-chain aspartic acid-bond isomerization to break the dominant helical
      structure of the N-terminal decapeptide fragment by CD. In the current study we
      use molecular modeling to show that insertion of the extra -CH2-group into the
      decapeptide backbone results in the formation of stable reverse-turns and
      destabilizes the helical conformer that competes with the extended structure at
      the full-sized peptide level. The molecular modeling also reveals a limited
      propensity of the diisomerized peptide to form extended structure directly. Anti
      A beta pAb 2332 is more sensitive for the non-isomerized status of the
      decapeptide than that of the full-sized peptide. mAb 6E10, raised against
      unmodified A beta recognizes only the unmodified decapeptide or the peptide
      isomerized at the first aspartic acid in a conformation-dependent manner, but
      does not recognize the mid-chain isomerized or diisomerized decapeptide in any
      circumstance. The diisomerized decapeptide was used as immunogen to generate
      polyclonal antibody 14943 that is not selective for the isomerized status of
      either the full-size peptide or the decapeptide, but recognizes the isomerized
      peptides preferentially when the peptide antigen structures are conserved during
      the enzyme-linked immunoassay procedure. Owing to the aberrant behavior of the
      full-sized A beta peptide during standard RP-HPLC, serum stability studies that
      indicate extracellular stability can be more effectively performed on the
      decapeptide fragments. Remarkably, the diisomerized peptide exhibits a
      significantly increased stability towards serum peptidases compared with the
      unmodified or monoisomerized peptides, suggesting a possible mechanism of the
      retention of the isomerized A beta peptide in the affected brains.

PMID- 8738656
TI  - Solution structure of the cytoplasmic domain of the human immunodeficiency virus
      type 1 encoded virus protein U (Vpu).
AB  - The HIV-1-specific Vpu protein is an 81 amino acid class I integral membrane
      phosphoprotein that induces degradation of the virus receptor CD4 in the
      endoplasmic reticulum and enhances the release of virus particles from infected
      cells. Vpu is of amphipathic nature and consists of a hydrophobic N-terminal
      membrane anchor proximal to a polar C-terminal cytoplasmic domain. In our recent
      work, focussed on the structural analysis of the cytoplasmic tail, we established
      an alpha-helix-flexible-alpha-helix-turn model. Now we present the experimental
      solution structure of the Vpu cytoplasmic domain which has been elucidated in
      aqueous 50% trifluoroethanol solution by 2D 1H NMR spectroscopy, and restrained
      molecular dynamics and energy minimization calculations. Under these conditions
      the peptide, Vpu32-81, is predominantly monomeric and adopts a well defined helix
      interconnection-helix-turn conformation, in which the four regions are bounded by
      residues 37-51, 52-56, 57-72 and 73-78. The presence of the cis isomer of Pro-75
      manifests itself as a doubling of cross peaks of neighbouring residues in the 2D
      spectra. A related variant peptide, Vpum32-81, in which the Vpu-phosphoacceptor
      sites Ser52 and Ser56 were exchanged for Asn, adopts a very similar structure
      and, taken together, provides evidence that the second helix and the turn form a
      comparatively rigid region. Both helices are amphipathic in character, but show
      different charge distributions. In general the cytoplasmic region is N-terminally
      positively charged, passes through a region of alternating charges in helix 1 and
      then becomes negatively charged. The flexibility of the interconnection permits
      orientational freedom of the two helices. The motif found here is the first
      experimentally refined solution structure of the cytoplasmic domain of Vpu, and
      it is conceivable that these alpha-helices are important for a previously defined
      physical interaction with an alpha-helical Vpu-responsive element located within
      the cytoplasmic tail of CD4.

PMID- 8738657
TI  - Isolation and characterization of a trisulfide variant of recombinant human
      growth hormone formed during expression in Escherichia coli.
AB  - A new variant of human growth hormone was recently found [Pavlu, B. & Gellerfors,
      P. (1993) Bioseparation 3, 257-265]. We report here the identification and the
      structural determination of this variant. The variant, which is formed during the
      expression of human growth hormone in Escherichia coli, was found to be more
      hydrophobic than rhGH as judged by its prolonged elution time by hydrophobic
      interaction chromatography. The rhGH hydrophobic variant (rhGH-HV) was isolated
      and subjected to trypsin digestion and RP-HPLC analysis, resulting in an altered
      retention time of one single tryptic peptide as compared to the corresponding
      fragment of rhGH. This tryptic peptide constitutes the C-terminus (aa 179-191) of
      hGH and contains one of the two disulfide bridges in hGH, viz. Cys182-Cys189.
      Amino acid sequences and composition analyses of the tryptic peptide from rhGH-HV
      (Tv18-19) and the corresponding tryptic peptide from rhGH (T18+19) were
      identical. Electrospray mass spectrometry (ES MS) of Tv18+19 isolated from rhGH
      HV revealed a monoisotopic mass increase of 32.7, as compared to T18+19 from
      rhGH. A synthetic Tv18+19 peptide having a trisulfide bridge between Cys182 and
      Cys189 showed identical fragment in ES/MS compared to Tv18+19 isolated from rhGH
      HV, i.e. m/z 617.7 and 682.9. These fragments are formed through a unique
      cleavage in the trisulfide (Cys182-SSS-Cys189) bridge not found in the
      corresponding T18+19 disulfide peptide. Furthermore, the synthetic Tv18+19 co
      eluted in RP-HPLC with Tv18+19 isolated from rhGH-HV. Two-dimensional NMR
      spectroscopy of the synthetic T18+19 and Tv18+19 peptides were performed. Using
      these data all protons were assigned. The major chemical shift changes (delta
      delta > 0.05 ppm) observed were for the beta-protons of Cys182 and Cys189 in
      Tv18+19 as compared to T18+19. CD spectroscopy data were also in agreement with
      the above results. Based on these physico-chemical data rhGH-HV has been
      structurally defined as a trisulfide variant of rhGH. The receptor binding
      properties of rhGH-HV was studied by a biosensor device, BIAcore. The binding
      capacity of rhGH-HV was similar to rhGH with a binding stoichiometry to the
      rhGHBP of 1:1.6 and 1:1.5, respectively, indicating that the trisulfide
      modification did not affect its receptor binding properties.

PMID- 8738658
TI  - A long-term follow-up study of asymptomatic hematuria and/or proteinuria in
      adults.
AB  - Between January 1, 1983 and December 31, 1992, 805 patients with asymptomatic
      proteinuria and/or hematuria were selected in the mass screening of 56,269
      adults. We conducted prospective long-term follow-up studies of these patients
      and evaluated their clinical findings and renal histology. They were divided into
      three groups according to the first dipstick urinalysis findings: 478 patients
      with pure hematuria (H), 150 patients with concomitant hematuria and proteinuria
      (H & P), and 177 patients with proteinuria (P). The mean follow-up period was
      5.80 +/- 4.42 years. Of the 478 patients with H, a specific cause of hematuria
      was found in 46 (9.6%), the remaining 432 (90.4%) patients were diagnosed as
      having asymptomatic hematuria (ASH). During the follow-up period, in the ASH
      patients, hematuria disappeared in 44.2%, 43.7% had persistent microhematuria
      without proteinuria, and 10.6% manifested proteinuria, none of the patients
      showed renal insufficiency. Of the 150 patients with H & P, 134 were diagnosed as
      having asymptomatic H & P. During the follow-up period, the hematuria and
      proteinuria disappeared in 16.4% of these patients, the proteinuria disappeared
      in 8.2%, and 14.9% of the patients showed renal insufficiency. Of the 177
      patients with P, 151 were diagnosed has having asymptomatic P. During the follow
      up period, proteinuria disappeared in 23.2%, and 10.6% showed renal
      insufficiency. Renal biopsy was performed in 151 patients in the study population
      who had a moderate degree of proteinuria; 68.2% of these patients had IgA
      nephropathy, 12.6% had non-IgA mesangial proliferative GN, 6.0% had membranous
      nephropathy, 5.3% had minimal change, and 2.6% had focal and segmental glomerular
      sclerosis. This study of the mass screening of urinalysis in asymptomatic adults
      showed that although the patients with pure hematuria did not exhibit renal
      insufficiency, 10.6% of these patients were proteinuric during the follow-up
      period. Therefore, careful observation and management are needed in these
      patients.

PMID- 8738659
TI  - Point mutation in the alpha-galactosidase A gene of atypical Fabry disease with
      only nephropathy.
AB  - A point mutation in exon 6 of the alpha-galactosidase A gene (alpha-GAL A) was
      found in a Japanese hemizygous male without typical manifestations of Fabry
      disease other than renal involvement. This 45-year-old man developed moderate
      proteinuria and was diagnosed with Fabry disease on the basis of renal histologic
      findings and prominent decreases in alpha-GAL A activity in his plasma, urine,
      leukocytes, and skin fibroblasts. Determination of the cDNA sequence of his alpha
      GAL A gene revealed substitution of a G to A in codon 301, resulting in a
      glutamine rather than an arginine residue. Our case is unique in that this
      patient only demonstrated renal manifestations while all other reported patients
      with atypical Fabry disease, including a case with the identical point mutation,
      present with a cardiomyopathy. Direct DNA sequencing of exon 6 and measurement of
      alpha-GAL A activity among the patient's family confirmed that the mutation was
      transmitted from his mother.

PMID- 8738660
TI  - Effect of amino acid based dialysate on peritoneal blood flow and permeability in
      stable CAPD patients: a potential role for nitric oxide?
AB  - Amino acid dialysis solution 1.1% (Nutrineal) contains L-arginine, a substrate
      for nitric oxide (NO) synthesis. NO causes vasodilation in many organs. To
      investigate effects of the amino acid dialysis solution on peritoneal
      permeability and perfusion, standard peritoneal permeability analyses were
      performed in 10 stable CAPD patients; one with Nutrineal and another with glucose
      dialysate (Dianeal 1.36%). The mass transfer area coefficient (MTAC) of nitrate
      and cGMP were calculated to study a possible role of NO. The MTAC of CO2 was
      measured to estimate peritoneal blood flow. The MTAC of CO2 was higher during the
      4-hour dwell with the amino acid solution: median 93 ml/min (amino acid solution)
      vs. 60 ml/min (glucose solution); p < 0.01. This suggests an increased peritoneal
      blood flow during the administration of amino acids. Also the MTACs of low
      molecular weight solutes were greater with amino acids compared to glucose:
      creatinine 11.6 ml/min vs. 10.0, urea 19.0 vs. 16.6, urate 9.5 vs. 8.0; p < or =
      0.01 for all. This points to an increased effective peritoneal surface area
      during amino acids. The clearances of the macromolecules beta 2-microglobulin and
      alpha 2-macroglobulin were also greater with the amino acid dialysis solution (p
      < 0.05), but there was only a small increase in the clearances of albumin and
      IgG. The increase in albumin loss during the 4-hour dwell with amino acids was
      only marginal. The MTACs of nitrate and cGMP were similar with the 2 solutions,
      without evidence of local production of these solutes. No difference was found
      between the 2 solutions in the dialysate concentrations of the prostaglandins
      PGE2, 6-keto-PGF1 alpha, PGF2 alpha and TxB2. The transcapillary ultrafiltration
      rate was higher during the amino acid dwell (p < 0.01), but no significant
      difference in net ultrafiltration was found, because the lymphatic absorption
      tended to be slightly greater with amino acids. The difference in transcapillary
      ultrafiltration with the 2 solutions was probably blood flow dependent, as the
      peritoneal filtration fraction was essentially the same in the 2 experiments. It
      is concluded that amino acid dialysis solution had a vasoactive effect. It mainly
      influenced the peritoneal blood flow and the effective peritoneal surface area.
      These effects could not be attributed to NO, as judged from nitrate or cGMP
      MTACs.

PMID- 8738661
TI  - Six-month overnight administration of intraperitoneal amino acids does not
      improve lean mass.
AB  - Intraperitoneal administration of 1% amino acid dialysis solution in patients on
      continuous peritoneal dialysis (CAPD) is associated with improvement in plasma
      amino acid concentrations and inconsistent results with respect to nitrogen
      balance. Whether alteration(s) in lean mass and body fat distribution also occur
      remains controversial. Therefore 18 patients (P), on CAPD for at least 6 months,
      were assigned in a prospective and controlled fashion to receive overnight either
      a 1% amino acid (AA-P) or a 1.36% glucose (Glu-P) containing dialysis solution.
      Body composition was investigated using whole body dual energy X-ray
      absorptiometry (Hologic QDR 1000/W). In P receiving glucose (n = 9), total body
      fat mass increased (+1.0 +/- 0.4 kg, mean +/- SEM, p < 0.03), whereas in patients
      on amino acids (n = 9), it decreased (-0.6 +/- 0.3, p < 0.02). This decrease in
      fat mass in AA-P was attributable to a decrease in upper body fat (-0.6 +/- 0.2,
      p < 0.02), whereas in Glu-P, it increased (+0.9 +/- 0.03, p < 0.03). No change in
      lower body fat was observed in either group. Total body lean mass remained
      similar in both groups during the six months of study (AA-P: 46.6 +/- 2.9 kg vs
      47.0 +/- 3.0 kg, Glu-P 50.8 +/- 3.2 vs 50.1 +/- 2.2 kg baseline vs 6 months,
      respectively). In AA-P plasma urea concentrations increased from 25 +/- 2 to 34
      +/- 3 mmol/l (p < 0.05), whereas plasma bicarbonate concentrations were similar
      before and after 6 months of therapy in either group. Plasma albumin and
      transferrin concentrations did not change in either group. Protein catabolic rate
      increased in AA-P (p < 0.01), whereas K x t/V did not change as a consequence of
      either therapy. CONCLUSION: Reduction in the amount of glucose in the peritoneal
      dialysate and the addition of amino acids decreases, whereas continuous dialysis
      with overnight glucose increases upper body fat over a 6-month period. However,
      no changes in protein stores were observed with the addition of amino acids.
      Therefore overnight peritoneal dialysis with amino acids offers minor advantages
      to protein-malnourished patients on CAPD, but may be of benefit in overweight
      CAPD patients.

PMID- 8738662
TI  - The effects of hemodialysis on duodenal and gastric mucosal changes in uremic
      patients.
AB  - From March 1992 to July 1992, 30 uremic patients (15 dialysed, 15 non-dialysed)
      and 15 non-uremic patients who had dyspeptic complaints were compared in terms of
      gastric and duodenal diseases. Gastritis and duodenitis graded as I, II and III
      were not found different in three groups (p > 0.05). Although the incidence of
      peptic ulcer disease is very high in both groups of uremic patients in comparison
      with the controls, there was no significant difference between two uremic groups
      (p > 0.05). Also the prevalence of gastritis determined histologically was not
      different in dialysed and non-dialysed uremic patients (p > 0.05). The incidence
      of the histologically proven gastritis was found higher in uremic patients than
      in non-uremic patients (p < 0.05). But, there were no significant differences
      among the three groups with regard to the rate of histologically proved
      duodenitis (p > 0.05). Gastrin levels, urea positivity, the incidence of
      gastritis and duodenitis and peptic ulcers did not differ in both uremic groups.
      However, these values were found significantly high in the uremic patients when
      compared to non-uremics. These findings showed serum gastrin levels, H.-pylori
      infection, gastritis and duodenal disease in the uremic patients to be higher
      than those of the control group. Moreover, no effect of hemodialysis treatment on
      these results was observed.

PMID- 8738663
TI  - Blood recirculation in temporary central catheters for acute hemodialysis.
AB  - The low-flow method has been shown as a reliable evaluation of access
      recirculation. Few data is available on temporary central catheter blood
      recirculation; results of 2% and 4% have been reported in subclavian, 10% in 24
      cm long femoral, and 18% in 15 cm long femoral catheters, mostly in indwelling
      catheters for chronic hemodialysis. The purpose of this prospective study was to
      evaluate blood recirculation in a larger number of recently inserted temporary
      intravenous catheters for acute hemodialysis, comparing subclavian and femoral
      sites. Fifty blood recirculation measurements were performed in 38 different
      temporary central venous dialysis catheters inserted in thirty-one critically ill
      patients from medical and surgical intensive care units presenting acute renal
      failure supported by intermittent hemodialysis. All the catheters used were well
      functioning 11.5 French dual lumen Quinton of 13.5 or 19.5 cm length. Catheters
      presenting mechanical dysfunction, which did not allow a blood flow rate of 300
      ml/min or for which lines had to be reversed were excluded from the analysis.
      Access blood recirculation was measured shortly after catheter insertion
      according to the low flow method applied after the first 30 minutes of
      hemodialysis at a blood flow rate of 300 ml/min. Mean blood recirculation for the
      50 measurements was 10.3 +/- 9.2%. It was significantly higher in the 26 femoral
      catheters than in the 24 subclavian catheters, reaching respective means of 16.1
      +/- 9.1% and 4.1 +/- 3.6% (p = 0.0001). Blood recirculation rate was not
      different between 13.5 cm and 19.5 cm long subclavian catheters (3.0 +/- 2.6%, n
      = 13, versus 5.4 +/- 4.3%, n = 11, respectively), but was significantly higher in
      13.5 cm long femoral catheters (22.8 +/- 9.1%, n = 9, versus 12.6 +/- 6.9%, n =
      17) (p = 0.004). Blood recirculation was measured on two separate occasions in 12
      catheters randomly selected (5 femoral and 7 subclavian catheters); the obtained
      results were reproducible with a mean difference of only 2.1 +/- 1.8% between the
      two measurements and a correlation of 0.96. The mean time elapsed between
      catheter insertion and recirculation assessment was 2.2 +/- 3.1 days and was
      similar for femoral and subclavian catheters. No correlation was found between
      the percentage of recirculation and the arterial and venous resistances recorded
      during dialysis session or with the time from catheter insertion. Mean urea
      reduction ratio (URR) for the 50 dialysis sessions was 57.8 +/- 13.0%. It was
      significantly higher for sessions performed with subclavian than with femoral
      catheters (62.5 +/- 10.9%, n = 24, versus 54.5 +/- 14.2%, n = 26) (p = 0.03). In
      conclusion, the expected blood recirculation in well-functioning and recently
      inserted temporary dialysis catheters is under 5% for subclavian, over 12% in
      19.5 cm femoral, and over 22% in shorter 13.5 cm femoral catheters at a blood
      flow rate of 300 ml/min. The consequently reduced dialysis efficiency with
      femoral catheters is another factor to be considered in the choice of a site for
      temporary dialysis catheter insertion in acute renal failure patients,
      particularly when dialysis dose delivery is a priority, such as intoxication
      cases treated by extracorporeal therapy.

PMID- 8738664
TI  - Weight reduction and fluid intake in an obese and fluid noncompliant ESRD
      patient.
AB  - This case study describes the application of a behavioral weight reduction
      program to an obese ESRD patient who was also fluid noncompliant. The major
      purpose of the study was to determine whether the behavioral weight reduction
      program could be successfully applied to a hemodialysis patient, and if so, what
      effect reduced caloric intake would have on fluid intake. Based on animal and
      human studies showing a strong relation between eating and drinking, it was
      expected that body weight reduction would be accompanied by reduced fluid intake.
      On the other hand, an alternative psychological hypothesis suggested that
      increased fluid intake might be substituted for reduced food intake. The results
      of the weight reduction program indicated that a successful weight reduction of
      42 lbs was maintained over an 18-month follow-up period. However, fluid intake
      increased during periods when caloric intake was reduced. Overall, the results
      indicated that behavioral weight reduction programs can be successfully applied
      to weight reduction in obese hemodialysis patients but that ways to avoid
      increased fluid intake need to be carefully addressed by such programs.

PMID- 8738665
TI  - Conversion to microemulsion cyclosporine in stable renal transplant patients:
      results after one year.
AB  - We switched 302 renal transplant patients from the conventional to a new
      microemulsion formulation of cyclosporine, to study the latter's safety and
      efficacy. We used a simple 1:1 conversion of the patient's total daily dose. We
      measured trough drug levels as well as serum creatinine, liver enzymes, uric
      acid, and blood pressure values at baseline and at days 4, 8, 15, 29, and months
      3, 6 and 12 after drug substitution. Dose adjustments directed at trough levels
      80-120 ng/ml were performed, starting at day 8. Within the 12-month observation
      period, the cyclosporine dose was reduced by 14.7% (204 +/- 60 mg/day baseline vs
      174 +/- 51 mg/day after conversion, p < or = 0.001). By day 8, the 1:1 dosage
      conversion resulted in a modest mean increase in drug trough levels (114 ng/ml
      baseline vs 120 ng/ml, p < or = 0.01). This increase was accompanied by an
      increase in serum creatinine concentration, a decrease in calculated creatinine
      clearance, and an increase in uric acid values (p < or = 0.05). Liver enzymes
      remained unchanged while systolic and mean arterial blood pressure decreased (p <
      or = 0.05). After one month, drug trough levels had decreased to baseline (112
      ng/ml) and remained there until month 6. They were significantly lower after 12
      months (102 +/- 33 ng/ml, p < or = 0.001). Plasma creatinine values decreased to
      below baseline by month 6 (p < or = 0.001) and month 12 (p < or = 0.001). Twenty
      four (8%) biopsy proven rejection episodes and 7 cases of cyclosporine attributed
      nephrotoxicity occurred in these 302 patients within these 12 months. We
      conclude, that a 1:1 conversion from conventional to the microemulsion form of
      cyclosporine is efficacious and safe. However, we advise an initial 10% decrease
      in dose reduction in those patients whose trough levels are in the high-normal
      range.

PMID- 8738666
TI  - Experimental and clinical experience with the use of tacrolimus (FK506) in kidney
      transplantation.
AB  - Tacrolimus is a recently developed immunosuppressive agent, based on a mechanism
      similar to cyclosporin. A broad variety of trials has provided evidence for its
      efficacy in human liver transplantation. In these trials, the incidence of acute
      rejection was markedly reduced. The following article reviews recent knowledge
      regarding clinical and experimental experience with tacrolimus in kidney
      transplantation. In summary, clinical trials suggested a marked reduction of
      acute allograft rejections comparable to those observed in liver transplantation.
      Its efficacy in steroid-resistant rejections is also well documented, while not
      critically analyzed in a prospective trial. Its effect is independent of the
      preceding administration of antilymphocyte antibodies. Thus, its use seems
      warranted even in the presence of steroid-resistant graft rejection, when
      treatment with antilymphocyte antibodies is contraindicated. Based on preliminary
      experience with tacrolimus in previous studies of primary immunosuppressive
      treatment and on the compelling evidence that the drug is effective in rescue
      therapy, its use as primary immunosuppressive regimen in immunologic high risk
      patients should now be considered.

PMID- 8738667
TI  - A review of clinical experience with the novel immunosuppressive drug
      mycophenolate mofetil in renal transplantation.
AB  - This review gives a summary about the current knowledge on the novel
      immunosuppressive drug mycophenolate mofetil (RS61443) in renal transplantation.
      The results of the preclinical pilot trials and of the so far published pivotal
      study for the prevention of rejection are described. Mycophenolate mofetil (MMF),
      the 2-4-morpholino ethyl ester of mycophenolic acid, is an inhibitor of the
      Inosine Monophosphate Dehydrogenase, an enzyme in the de novo synthesis of
      purines. MMF showed no clinical significant interactions with a variety of
      medications used in renal transplantation. Following oral administration it is
      rapidly absorbed. Pilot studied suggested a significant reduction in the
      incidence of rejection at doses of 2 g/day. 491 patients were enrolled in a
      randomized, double blind, multicentre, placebo-controlled study of the addition
      of mycophenolate mofetil to cyclosporine and oral corticosteroids for the
      prevention of acute renal allograft rejection. After six month the rates for
      biopsy proven rejection were the following: placebo 46.4%, MMF 2 g 17.0% and MMF
      3 g 13.8%. The adverse event profile resembles that of triple therapy with
      azathioprine. Most adverse events concerned the gastrointestinal tract, the hemic
      system and opportunistic infections. MMF offers an improved immunosuppressive
      therapy following renal transplantation.

PMID- 8738668
TI  - Influence of cyclosporine A and FK506 on 24 h blood pressure monitoring in kidney
      transplant recipients.
AB  - Cyclosporine A (CsA) seems to exert direct effects on blood pressure and diurnal
      blood pressure alterations. After kidney transplant about 60% of the recipients
      are suffering from such alterations. In the present study, blood pressure
      profiles of 15 FK506-treated kidney transplant patients were compared to
      recipients with CsA immunosuppression. Both groups showed no statistical
      differences in number, kidney function, age, body weight, sex distribution and
      time after transplantation. Mean arterial blood pressure in FK506-treated
      patients at daytime was 105 +/- 2.5 mmHg, at night 109 +/- 3.0 mmHg. Systolic
      blood pressure difference was 2.3 mmHg, diastolic day/night blood pressure
      difference 0.6 mmHg, and the difference of the heart frequency 6.8 beats/min.
      Cyclosporin A-treated patients showed a mean arterial blood pressure during the
      day of 107 + 2.6 mmHg, at night-time a mean arterial blood pressure of 107 + 3.4
      mmHg was measured. The diurnal blood pressure alterations of systolic blood
      pressure were 0.9 mmHg, diastolic blood pressure difference 3.5 mmHg
      respectively, the heart frequency showed a difference of 4.4 beats/min. Both,
      FK506-treated patients and patients with CsA immunosuppression exhibit reduced
      diurnal blood pressure alterations. Furthermore, mean arterial pressure in both,
      FK506 and CsA-treated patients was elevated and showed no statistical differences
      between the groups. In FK506-treated patients, however, antihypertensive therapy
      was less intensive. Concerning arterial blood pressure and diurnal blood pressure
      alterations, FK506 offers no advantages as compared to cyclosporine A. The
      reduced usage of antihypertensive drugs, however, may give evidence for lower
      hypertensive properties of FK506 as compared to CsA.

PMID- 8738669
TI  - The influence of the immunosuppressants OKT3 and ATG on immunological parameters.
AB  - Cytokines play an important role in the immune response induced by organ
      grafting, particularly during episodes of rejection. We tested the influence of
      monoclonal and polyclonal antibodies upon levels of mediators of the immune
      system. In 29 patients various cytokines and mediators were serially analyzed
      following transplantation. Thirteen patients received polyclonal antibodies (ATG)
      and 7 monoclonal (OKT3). Both OKT3 and ATG induced a rise in body temperature.
      Mean serum levels of amyloid A, neopterin, plasma levels of TNF alpha,
      interleukin 2 receptor (IL-2R) and urine levels of interleukin 6 (IL-6) and IL-2R
      were elevated when antibodies were employed. Interestingly, urine and plasma TNF
      alpha as well as urine IL-6 and IL-2R remained elevated following ATG but not
      OKT3 and did not rise in case of basic treatment. In summary, antibody therapy
      increased levels of immune mediators. These mediators remained elevated following
      the discontinuation of treatment in case of ATG but not OKT3.

PMID- 8738670
TI  - Pharmacokinetic profile of cyclosporine A after conversion to Sandimmun Optoral:
      influence on ambulatory blood pressure in renal transplant patients.
AB  - The aim of the present study was to investigate whether the pharmacokinetic
      profile of cyclosporin A under Sandimmun Optoral compared to Sandimmun has an
      effect on blood pressure in patients with stable renal allograft function. Twenty
      eight patients were randomized into two groups. Two pharmacokinetic profiles (I,
      II; time interval 7 days) were obtained in each group. One group (n = 18) was
      switched from Sandimmun to an equal dose (1:1) of Sandimmun Optoral after the
      first kinetic and the other (n = 10) received Sandimmun for both kinetics. Eight
      blood samples were taken during each kinetic and cyclosporine values were
      measured. Ambulatory blood pressure measurement was performed during each
      kinetic. There were no differences in the pharmacokinetic parameters between
      kinetics I and II in the control group but significant differences in the
      switched group with increased Cmax (+64%), AUC (+44%), C0 (+17%) and decreased
      Tmax (-39%) in kinetic II compared to kinetic I. Correlation of C0 with AUC was
      stronger for Sandimmun Optoral (r = 0.792) than for Sandimmun (r = 0.718).
      Correlation of C0 with Cmax was similar for Sandimmun Optoral (r = 0.53) and
      Sandimmun (r = 0.56). Mean 12 h blood pressure of kinetic II tended to be lower
      than that of kinetic I in the control group, but the opposite was true for the
      switched group. When blood pressure levels around Tmax +/- 1 h were analyzed
      only, RR (syst/diast) in mmHg was 135 +/- 3.7/89 +/- 2.2 (kinetic I) and 130 +/-
      2.8/85 +/- 2.8 (kinetic II) for control as compared to 134 +/- 2.4/85 +/- 2.9 and
      137 +/- 3.1/86 +/- 2.8 for the switched group, respectively. Sandimmun Optoral
      shows an improved pharmacokinetic profile. However, higher blood concentrations
      of cyclosporine under Sandimmun Optoral tend to increase slightly systemic blood
      pressure as compared to that under Sandimmun.

PMID- 8738671
TI  - Initial experience with tacrolimus rescue therapy in OKT3 resistant rejection.
AB  - Follow-up of 9 renal transplant recipients who were converted from cyclosporin A
      to tacrolimus (FK506) as recue therapy for intractable rejection is described.
      All patients initially received a cyclosporin A based immunosuppression. They
      developed biopsy proven acute rejections 22 +/- 11 days after transplantation
      which did not resolve by i.v. steroids and subsequent OKT3. Fifty-three +/- 11
      days post transplantation the patients were converted from cyclosporin A to
      tacrolimus. After conversion to tacrolimus 6 patients developed a stabile
      transplant function. One transplant recipient who initially responded to
      tacrolimus lost his graft due to a chronic rejection 9 months following
      conversion. Two patients with never functioning kidneys remained on dialysis
      despite tacrolimus therapy. After conversion no serious adverse events occurred
      and only a slightly increased infection rate and hyperglycemia were noted as
      major side effects of tacrolimus. Tacrolimus rescue therapy was effective in
      treating acute renal allograft rejection unresponsive to steroids and OKT3.
      Tacrolimus rescue therapy was not accompanied by a substantial rise in
      complications. Patients with never functioning kidneys did not seem to benefit
      from tacrolimus rescue therapy.

PMID- 8738672
TI  - Effects of mycophenolic acid mofetil on acute rejection of kidney allografts in
      rats.
AB  - Mycophenolic acid mofetil (MMF) is an agent which has recently gained a lot of
      attention. In clinical trials MMF has reduced the rate of acute rejection
      episodes in human recipients of kidney allografts by inhibiting inosin
      monophosphat-dehydrogenasis (IMPDH), an enzyme involved in the purin metabolism
      and related to the expression of adhesion molecules. The aim of the present study
      was to analyze the effects of MMF upon the expression of adhesion molecules in
      transplanted kidney allografts. LBNF1 kidneys were orthotopically transplanted
      into Lewis rats and either treated with MMF (20 mg/kg/day) or vehicle. Rats were
      harvested 3, 5 and 7 days following transplantation. Immunohistology was
      performed with various monoclonal antibodies. In general, MMF resulted in a
      better preservation of graft structure by 7 days. Cellular infiltration and
      tubular atrophy were less pronounced. At day 3, macrophages were diminished in
      MMF-treated animals to a high extent, while the number of T-cells was almost
      identical as compared to controls. In addition, the number of cells positive for
      MHC class II and LFA-1 was reduced in the MMF-treated animals. In conclusion, MMF
      resulted in a markedly reduced leukocyte infiltrate, presumably based on a
      reduced expression of lymphocytic adhesion molecules and an interaction with
      macrophages.

PMID- 8738673
TI  - Assessment of chronic rejection in permanent accepted renal allografts in anti
      CD4 treated rats.
AB  - In rats, transient prophylactic anti-CD4 therapy with the nondepleting mAB RIB5/2
      prevents acute rejection of MHC-mismatched allografted kidneys and induces long
      lasting unresponsiveness. However, little is known about long-term benefits of
      this prophylactic anti-CD4 regimen. Here we report experimental results of
      permanently accepted rat renal allografts after prophylactic anti-CD4 treatment
      in regard to signs of chronic rejection. Kidneys from Wistar Furth donors were
      orthotopically grafted into bilateral nephrectomized BDIX recipients under the
      cover of anti-CD4 treatment (20 mg/kg b.w). Kidney function was serially
      monitored by measurement of serum creatinine and urine protein excretion. After
      100 or 300 days respectively renal allografts were harvested, histologically and
      immunohistologically assessed and intragraft cytokine gene expression determined.
      Serum creatinine increased in few allografted rats. 30% of the 300-day-old grafts
      had an increased proteinuria and higher degrees of glomerular sclerosis. In these
      grafts cellular infiltration was more pronounced. However, no activated
      leukocytes (IL-2 receptor positive) were detected. Correspondingly, intragraft
      gene expression of CD3, IL-10 and IFN gamma was low. The results of our study
      indicate that a prophylactic anti-CD4 regimen diminishes chronic rejection to a
      level comparable to isografted or naive mass-reduced or ischemic kidneys. Thus,
      the signs of chronic rejection observed seem to be mainly caused by alloantigen
      independent processes.

PMID- 8738674
TI  - Goitre and severe autonomic neuropathy due to secondary amyloidosis in a renal
      transplant patient.

PMID- 8738675
TI  - Angiotensin converting enzyme inhibitor improves nephrotic syndrome associated
      with cyanotic congenital heart disease.

PMID- 8738676
TI  - Clearance of fluoride by hemodialysis.

PMID- 8738677
TI  - Glycine irrigant absorption syndrome following cystoscopy.

PMID- 8738678
TI  - Use of vancomycin in dialysis patients.

PMID- 8738679
TI  - Temporomandibular joint disc position in the sigittal and coronal plane. A
      macroscopic and radiological study.

PMID- 8738681
TI  - Better standardisation will improve the quality of analgesic studies.

PMID- 8738680
TI  - The mandibular third molar. Dentists' judgment in the removal of asymptomatic
      molars.

PMID- 8738682
TI  - Additive analgesic effect of codeine and paracetamol can be detected in strong,
      but not moderate, pain after Caesarean section. Baseline pain-intensity is a
      determinant of assay-sensitivity in a postoperative analgesic trial.
AB  - BACKGROUND: A randomized, double-blind, placebo-controlled single oral dose study
      was done in order to examine whether codeine has an additive analgesic effect to
      that of paracetamol for moderate and strong postoperative pain after abdominal
      surgery. The maximum recommended single dose of paracetamol 1000 mg (Paracet) was
      compared with a combination of a submaximal dose of paracetamol 800 mg plus
      codeine 60 mg (Paralgin forte) and placebo for pain relief after Caesarean
      section in 125 patients. METHODS: Visual analogue pain intensity score (VAS 0-100
      mm) and categorical pain relief score were recorded for 6 hours after the study
      drug intake. The main efficacy variables analyzed were: pain intensity difference
      and summed pain intensity differences during the first 3 and 6 h after study drug
      intake, total pain relief during the first 3 and 6 h, global evaluation score at
      the end of the observation period, and time to rescue analgesic. RESULTS: Because
      of protocol violations, 17 patients were excluded from the analysis of effects.
      Among the 108 patients included in the analysis of analgesic effect, 49 patients
      had moderate baseline pain (VAS between 40 and 60 mm on a 100 mm scale), and 59
      patients had strong baseline pain (VAS more than 60 mm). In patients with strong
      baseline pain, statistically highly significant differences were documented in
      efficacy variables between the active drugs and placebo and between the two
      active drugs. However, in patients with moderate baseline pain, no differences
      were found between the study drugs in any of the analgesic efficacy variables.
      CONCLUSION: This study thus confirms that codeine has additive analgesic effect
      to paracetamol in pain after surgery. Our results show the importance of initial
      pain intensity in postoperative assessment of analgesic drugs. Assay-sensitivity
      and test power are increased by selecting patients with sufficiently high initial
      pain intensity and by comparing groups of patients with identical surgery and
      similar demographic variables.

PMID- 8738683
TI  - Cardiovascular responses to experimental infra-renal aortic cross-clamping.
      Modulating effects of isoflurane, sodium nitroprusside and milrinone.
AB  - BACKGROUND: Pharmacological control of blood pressure is usually indicated during
      aortic cross-clamping (AXC). The aim of this study was to analyze the modulation
      by isoflurane (ISO), sodium nitroprusside (SNP) and milrinone (MIL) of the
      systemic circulatory responses to a standardized infra-renal AXC. METHODS:
      Chloralose-anaesthetized pigs were exposed to AXC at control (no vasoactive
      drugs) and during the administration of each of the drugs. RESULTS: During
      control, AXC increased mean arterial pressure (MAP, 17 +/- 4%) and systemic
      vascular resistance (SVR, 27 +/- 7%), but induced no significant changes in
      cardiac output (CO), heart rate (HR), pulmonary arterial pressures, pulmonary
      vascular resistance or central venous pressure. Low-dose ISO (0.7%) and
      investigated doses of SNP and MIL did not significantly alter this response. High
      dose ISO (1.4%, attenuated the AXC-induced increase in SVR, but not in MAP. All
      drugs decreased non-clamp MAP levels. Therefore, with low-dose ISO and with SNP
      or MIL, peak MAP during AXC was not significantly different from control non
      clamp levels (i.e. prior to pharmacological or surgical interventions). High-dose
      ISO was associated with a MAP during AXC that was below control non-clamp levels.
      CONCLUSIONS: The objective that during AXC MAP should not exceed control non
      clamp levels was achieveable by ISO, SNP or MIL. The modulating actions of the
      drugs on MAP during AXC were exerted mainly through reductions in non-clamp
      levels. This systemic hypotension was associated with decreased CO and SVR during
      ISO, and with decreased SVR and increased HR during SNP and MIL. Attenuation of
      the AXC-induced increase in SVR was produced only by 1.4% ISO.

PMID- 8738684
TI  - A cost-benefit evaluation of using propofol and alfentanil for a short
      gynecological procedure.
AB  - It is well established that the immediate recovery after propofol or alfentanil
      anesthesia is short. Although the drugs themselves are more expensive than older
      drugs, a potential for saving costs arises. Concerning the benefits in terms of
      late recovery, less information is available. With vaginal termination of
      pregnancy (VTP), anesthesia is supposed to be the major cause of sick-leave. Does
      propofol and alfentanil anesthesia for VTP reduce sick-leave compared with
      thiopental and nitrous oxide anesthesia, and do the increased costs of the drugs
      outweigh the reduced costs of sick-leave? Data were obtained from 39 of 40
      patients in ASA class I accepted for VTP and allocated to either propofol and
      alfentanil anesthesia (PA) or thiopental and nitrous oxide anesthesia (TN). A
      questionnaire was filled in by the patients at home after regaining full fitness.
      The number of patients with a sick-leave of 2 days or less in the groups was
      compared statistically with the number of patients with 3 days or more off work.
      The economic impact from the reported sick-leave was calculated for each study
      group, using data from national statistics. The figures were compared with the
      calculated costs of the drugs. The median number of days of sick-leave was 1 in
      the PA-group and 2 in the TN-group (range 0-3 and 0-5, respectively). Nineteen of
      the 20 patients in the PA-group and 13 of the 19 patients in the TN-group needed
      a short sick-leave period of 2 days or less (one-sided test of proportions, P <
      0.05). At the time of the study each patient was paid 210 SEK/day from the social
      insurance system and the mean cost of the drugs was 72 and 15 SEK/patient in the
      PA- and TN-groups, respectively. Using the mean difference in sick-leave between
      the groups of 0.8 days/patient (rather than the difference in median values of
      1), a net gain of 111 SEK/patient was the result of changing from thiopental
      nitrous oxide anesthesia to propofol-alfentanil anesthesia. Although the cost of
      drugs was higher, costs for the social insurance system and for the individuals
      themselves were reduced by almost 50%, when using the propofol and alfentanil
      combination, resulting in an overall benefit corresponding to almost twice the
      increase in the cost of anesthesia.

PMID- 8738685
TI  - Preoperative evaluation of intubation conditions in patients scheduled for
      elective surgery.
AB  - Prediction of a difficult airway is a continuing problem. Several tests have been
      developed in order to overcome this problem. It has been proposed that using more
      than one test could increase the degree of predictability. One hundred patients
      scheduled for general surgery were successfully evaluated using three methods: 1.
      The size of the tongue in relation to the oral cavity (Mallampati gradation). 2.
      The thyromental and the mandibular length. 3. The atlanto-occipital angle. Seven
      patients had a difficult laryngoscopy and were difficult to intubate. It was
      possible to predict differenties in all seven patients, but it was found that
      only the Mallampati gradation and the atlanto-occipital angle contributed
      significantly to predictability. The cost of predicting further difficulties in
      all patients with a difficult laryngoscopy was a false positive prediction in a
      further 13 patients who had no problems with laryngoscopy or intubation. By
      increasing the specificity of the tests the number of false positive
      classifications could be reduced to 10 patients, but this would have led to the
      missing of one patient with a difficult laryngoscopy.

PMID- 8738687
TI  - The effect of succinylcholine on energy metabolism studied by 31P-NMR
      spectroscopy in rat denervated skeletal muscle.
AB  - BACKGROUND: The goals of this study were: (1) to demonstrate the differences of
      metabolic changes induced by succinylcholine (SCh) administration between normal
      and denervated muscle by 31P-NMR spectroscopy: (2) to determine whether three
      kinds of drugs (vecuronium, midazolam and magnesium sulfate) could prevent these
      metabolic changes. METHODS: Following unilateral sciatic nerve section, 20 male
      Wistar rats were studied at three-week intervals. After SCh 1 mg.kg-1 was
      administered intravenously, the changes of the inorganic
      phosphate/phosphocreatine (Pi/PCr) ratio, the beta ATP/(PCr+Pi) ratio, and
      intracellular pH were measured by 31P-NMR both in normal and denervated hind limb
      muscles of 5 rats. The other 15 rats were allocated to the pretreatment groups by
      the following drugs: vecuronium 0.02 mg.kg-1, midazolam 0.1 mg.kg-1 and magnesium
      sulfate 60 mg.kg-1. After pretreatment 3 min before SCh administration, we
      measured the same parameters by 31P-NMR. RESULTS: SCh administration did not
      change the Pi/PCr ratio in normal muscle, but significantly increased that in
      denervated muscle (P < 0.05). This increase of the Pi/PCr ratio was also observed
      in all pretreated groups but was minimal as compared with that in non
      pretreatment denervated muscle. CONCLUSION: These data suggested that SCh
      administration decreased the level of "energy reserve" in denervated muscle, and
      that this metabolic change was not totally inhibited by vecuronium, midazolam, or
      magnesium sulfate.

PMID- 8738686
TI  - Comparison of intubating conditions after rocuronium and suxamethonium following
      "rapid-sequence induction" with thiopentone in elective cases.
AB  - BACKGROUND: Rocuronium (Org 9426) was shown to have the fastest onset of action
      of all currently available non-depolarizing neuromuscular blocking drugs and to
      provide intubating conditions similar to those of suxamethonium 60 to 90 s after
      administration. We compared the intubating conditions after rocuronium and
      suxamethonium following rapid-sequence induction of anaesthesia. METHODS: Fifty
      unpremedicated patients of ASA physical status I or II, scheduled for elective
      surgery were studied. Anaesthesia was induced with thiopentone 6 mg kg-1 followed
      randomly by suxamethonium 1 mg kg-1 or rocuronium 0.6 mg kg-1 and, 45 s later,
      intubation was commenced. Muscle fasciculations, intubating conditions and
      intubation time, haemodynamic variables and oxygenation were assessed. RESULTS:
      Intubation time did not differ between suxamethonium (9.8 +/- 2.2 s) (mean +/-
      SD) and rocuronium (10.5 +/- 2.9 s), respectively. Intubating conditions were
      clinically acceptable (good or excellent) in all patients given suxamethonium and
      in 96% of the patients given rocuronium. However, the condition of the vocal
      cords was better (P < 0.05) and diaphragmatic response to intubation was less
      pronounced with suxamethonium (P < 0.05). Changes in heart rate and arterial
      blood pressure were similar in both groups. CONCLUSION: The authors conclude that
      rocuronium is a suitable alternative to suxamethonium for rapid tracheal
      intubation even under unsupplemented thiopentone anaesthesia, at least in
      elective, otherwise healthy patients. Its use for rapid-sequence induction under
      emergency conditions, however, needs further investigation.

PMID- 8738688
TI  - Malignant hyperthermia (MH) diagnostics: a comparison between the halothane
      caffeine- and the ryanodine-contracture-test results in MH susceptible, normal
      and control muscle.
AB  - Recent studies demonstrated different contracture responses in muscle from
      malignant hyperthermia susceptible (MHS) compared to normal (MHN) individuals
      following exposure to the plant alkaloid ryanodine in-vitro. To confirm if
      ryanodine has a specific action in MHS muscle, the effect of a single
      concentration was investigated in skeletal muscle from MHS, MHN and control
      subjects using a new evaluation technique. In-vitro contracture test (IVCT) and
      MH diagnosis were performed according to the European Protocol in 86 patients
      sent to us for MH diagnostic testing and in 24 controls. Viable fresh muscle
      bundles were exposed to a single bolus of ryanodine 1.0 microM. Contracture onset
      time (OTp: defined as the time (min) from administration of ryanodine to the
      start of a contracture as measured by a contracture exceeding predrug baseline
      height), and the time to an increase of the baseline height to 10 mN above the
      predrug level (10Tp) were recorded. 29 patients were identified by IVCT to be
      MHS, 50 MHN, 7 MHE (equivocal) and 24 controls MHN. The indices from the
      ryanodine test separated all MHS (OTp: < 16 min; 10Tp < 27.4 min) from MHN (> 18
      and > 27.7 min) and control subjects (> 17.4 and > 29 min). Values for MHE
      (equivocal) individuals ranged from 17.1 to 27.8 min for the OTp and from 32 to
      49.2 min for the 10Tp. 5 patients with fulminant MH crises were included in the
      MHS group and showed the 95% confidence intervals (CI) of the median value < or =
      8.05 min (OTp) and < or = 13.35 min (10TP) for MHS. In contrast, CI of the median
      value for the control group were found to be > or = 25.2 min (OTp) and 43.15 min
      (10Tp) for normal muscle. Thus the ryanodine test protocol showed markedly
      different contractures in MHS and MHN or control muscle. These results suggest
      that MHS muscle has a higher sensitivity to ryanodine. However, the protocol
      should be investigated for reproducibility and validation of thresholds by other
      laboratories. Ryanodine can help to improve MH diagnostic tests.

PMID- 8738689
TI  - Rectal administration of morphine in children. Pharmacokinetic evaluation after a
      single-dose.
AB  - BACKGROUND: There is limited knowledge about the pharmacokinetics of morphine and
      its metabolites after rectal administration in children. In this study the
      pharmacokinetics of two different rectal formulations of morphine were examined
      and compared with intravenous morphine. METHODS: Children undergoing elective
      surgery received rectal morphine 0.2 mg/kg before start of surgery. Ten children
      (mean age 14 months) received morphine rectally in a hydrogel formulation and
      another 10 children (mean age 16 months) received morphine rectally in a
      parenteral formulation. For comparison, 6 children (mean age 21 months) were
      given the same dose intravenously. The plasma concentrations of morphine,
      morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were measured by
      HPLC over 6 h after drug administration. RESULTS: The mean rectal bioavailability
      of morphine was 35% (range 18-59) after hydrogel administration and 27% (range 6
      93) after the solution. Mean values of Cmax were 76 nmol/l (25-129) and 56 nmol/1
      (15-140), respectively. The results showed that morphine gel had a significantly
      higher bioavailability (P < 0.02) than the solution. The ratios of plasma (M3G +
      M6G) to morphine were higher after rectal administration (mean 7.5-8.7) than
      after i.v. injection (mean 5.3), indicating the presence of first-pass metabolism
      using the rectal route. CONCLUSIONS: The rectal morphine hydrogel has
      pharmacokinetic properties which makes it a useful formulation for premedication
      and pain alleviation in paediatric patients.

PMID- 8738690
TI  - MAC for halothane and isoflurane during normothermia and hypothermia in the
      newborn piglet.
AB  - BACKGROUND: Halothane and isoflurane are frequently used in studies of perinatal
      hypoxia and ischemia. Little information exists on the minimum alveolar
      concentration (MAC) necessary to prevent movement to a painful stimulus in
      newborn pigs and no information on the effects of hypothermia on MAC in pigs.
      Hypothermia is currently investigated as a posthypoxic neuroprotective
      intervention. METHODS: The MAC of halothane and isoflurane necessary to prevent
      movement when a 25 cm hemostatic clamp was applied to the tail were determined in
      six 20-48-hour-old piglets, and when the same stimulus was applied to the hoof.
      MAC for halothane was first determined at 39 degrees C, then at 35 degrees C,
      whereafter halothane was discontinued and MAC for isoflurane determined first at
      35 degrees C and then at 39 degrees C. RESULTS: In all six piglets MAC was lower
      at 35 degrees C than at 39 degrees C for both anesthetics with both tail and hoof
      determination, lower for halothane than isoflurane for both stimuli at both
      temperatures, and lower for tail than hoof determination for both anesthetics at
      both temperatures. For halothane at 39 degrees C, mean (SD) MAC hoof was 0.82
      (0.05)% vs tail 0.60 (0.12)%, and at 35 degrees C, hoof 0.65 (0.06)% vs tail 0.42
      (0.10)%. For isoflurane at 39 degrees C, MAC hoof was 2.47 (0.28)% vs tail 1.83
      (0.28)%, and at 35 degrees C, hoof was 1.83 (0.18)% vs tail 0.85 (0.25)%.
      CONCLUSION: In the newborn piglet, MAC should be determined by hoof clamp, MAC of
      isoflurane is approximately three times that of halothane, and both are reduced
      during hypothermia.

PMID- 8738691
TI  - Early cerebral functional outcome after coronary artery bypass surgery using
      different acid-base management during hypothermic cardiopulmonary bypass.
AB  - BACKGROUND: Cerebral injury can render meaningless an otherwise successful
      cardiac operation. As carbon dioxide management during hypothermic
      cardiopulmonary bypass has a major impact on cerebral blood flow during bypass,
      it may also influence postoperative cerebral function. The objective of this
      prospective, controlled, double-blind study was to compare the effect of pH-stat
      (temperature correction of blood gas analyses) or alpha-stat (no temperature
      correction) on brain function. METHODS: Cerebral function was assessed non
      invasively using neurological examination, a neuropsychological test battery,
      quantitative electroencephalogram and the cognitive evoked potential P300
      preoperatively and on postoperative day 7 or 8. Forty-five patients undergoing
      elective aortocoronary bypass grafting in barbiturate/opiate anesthesia were
      randomised into a pH-stat-(n = 23) and an alpha-stat-group (n = 22). Membrane
      oxygenators with arterial line filtration and non-pulsatile flow at a perfussion
      pressure of 50-60 mmHg were used throughout. RESULTS: One patient in each group
      developed a new paresis. Among 49 comparisons of cerebral function parameters,
      only 3 showed significant differences at the 5%-level, i.e. exactly what is
      expected purely by chance. These differences were too small to be clinically
      relevant and favored either pH-stat (theta-amplitude) or alpha-stat (subtest 3 of
      syndrome-short-test, number of mistakes in aiming). CONCLUSION: Under the bypass
      conditions of this study there was no difference in early cerebral functional
      outcome between pH-or alpha-stat carbon dioxide management during hypothermic
      cardiopulmonary bypass.

PMID- 8738692
TI  - Effect of inhaled nitric oxide on venous admixture depends on cardiac output in
      patients with acute lung injury and acute respiratory distress syndrome.
AB  - BACKGROUND: It has been shown that inhaled nitric oxide (NO) reduces
      intrapulmonary venous admixture (QVA/QT) and improves oxygenation in patients
      suffering from acute respiratory distress syndrome (ARDS). The change in QVA/QT
      during NO inhalation varies individually. Factors known to influence the
      respiratory response to NO are the NO concentration and the level of shunt before
      NO administration. Other factors that may modify the effect on gas-exchange
      during NO breathing are unknown. METHODS: We studied the effect of 40 ppm inhaled
      NO on pulmonary gas-exchange and haemodynamics in 37 patients with acute lung
      injury (ALI) and ARDS, respectively, and factors that may influence the
      respiratory response to NO. RESULTS: Inhalation of 40 ppm NO produced a decrease
      in mean pulmonary artery pressure (MPAP) from 33.1 +/- 7.2 to 30.2 +/- 6.8 (mean
      +/- SD) mmHg (P < 0.0001) while pulmonary artery wedge pressure (PAWP), cardiac
      output and mean arterial pressure remained constant. Change in QVA/QT during NO
      inhalation depended on the preinhalation cardiac output and had no association
      with mixed venous oxygen tension, MPAP-PAWP, and QVA/QT before NO delivery.
      QVA/QT decreased in 26 patients (group 1) and increased in 11 patients (group 2)
      during NO inhalation. In group 1, cardiac output was lower than in group 2 (8.6
      vs 12.2 l.min-1; P < 0.0005). CONCLUSION: We conclude that the change in venous
      admixture during inhalation of 40 ppm NO depends on cardiac output. If
      preinhalation cardiac output is high, 40 ppm NO can adversely affect gas exchange
      in patients with ALI and ARDS.

PMID- 8738693
TI  - Thermoregulatory response in female patients during lower abdominal surgery in
      the head-down tilt position.
AB  - BACKGROUND: The head-down tilt (HDT) position suppresses sympathetic nervous
      activity. We investigated the effect on thermoregulation of the HDT position
      during lower abdominal surgery under general anaesthesia. METHODS: Tympanic
      membrane temperature was measured to assess core temperature, and forearm
      fingertip and calf-toe temperature gradients were used to assess peripheral
      vasoconstriction in 30 female patients less than 60 years of age. RESULTS: During
      surgery in the HDT position (n = 10), the tympanic membrane temperature was
      similar to that of patients in the supine position (n = 10) (36.2 degrees C and
      36.2 degrees C), but in patients operated in the HDT position and premedicated
      with an angiotensin converting enzyme inhibitor (5 mg of enalapril, n = 10) it
      was reduced (35.7 degrees C, P < 0.05). In both groups of patients operated in
      the HDT position, forearm and calf skin-surface temperature gradients were lower
      by 2.3 degrees C than those in patients operated in the supine position (P <
      0.05). CONCLUSIONS: During lower abdominal surgery the head-down tilt position
      does not augment core hypothermia in spite of suppressed peripheral
      vasoconstriction, and the renin-angiotensin system may be of importance for
      thermoregulation.

PMID- 8738694
TI  - Propofol influences the electroretinogram to a lesser degree than thiopentone.
AB  - BACKGROUND: The Electroretinogram (ERG) is used clinically to assess the function
      of retina. Anaesthetic agents are known to affect ERG, and as anaesthesia is
      often needed in children and uncooperative patients, knowledge about its effects
      is of clinical importance. Barbiturates selectively depress ERG components, and
      we compared thiopentone with propofol to assess if the latter preserved retinal
      function better. METHODS: Ten pigs, average weight 17 kg (SD +/- 2 kg) were
      anaesthetized randomly with propofol 10 mg kg-1 or thiopentone 30 mg kg-1.
      Anaesthesia was maintained by 65% nitrous oxide in oxygen and continuous infusion
      of the induction agent, i.e. 10 mg kg-1 h-1 of propofol, or 10 mg kg-1 h-1 for
      the first hour, then 5 mg kg-1 h-1 of thiopentone, with doses being based on
      pilot studies. After an interval of one week the programme was repeated using the
      other agent. After 40 minutes dark-adaptation, responses to single flashes of
      graded intensities from a xenon flashlamp were recorded at five-minute intervals.
      The a- and b-wave amplitudes and implicit times (time to peak), and a-wave slopes
      were determined. RESULTS: The b-wave implicit time was significantly shorter
      during propofol anaesthesia than when using thiopentone. The effect was most
      pronounced at the lowest intensities (P < 0.01). No statistically significant
      differences were found in the amplitudes of the b-waves. The a-wave appeared at
      lower stimulus intensity (P < 0.05) and the a-wave slopes were significantly
      steeper (P < 0.01) during propofol anaesthesia. CONCLUSION: Propofol accordingly
      appeared to preserve the photoreceptor response better than thiopentone, and may
      therefore be considered to be more suitable for ERG recordings than thiopentone.

PMID- 8738695
TI  - Effect of nitrous oxide on human skeletal muscle function.
AB  - BACKGROUND: Nitrous oxide (N2O) is commonly administered in conjunction with
      parturition, which requires the performance of repeated high-force voluntary
      muscle actions. Therefore, we examined the effect of a subanesthetic dose of N2O
      on the force-velocity relationship of the quadriceps femoris muscle. METHODS:
      Nine healthy subjects performed maximal voluntary muscle actions once while
      breathing air and once while breathing a normoxic gas mixture containing 35%
      (N2O). Peak torque of the knee extensors was measured during concentric muscle
      contractions at different angular velocities (30, 60, 90, 150 and 210 degrees s
      1), and eccentric (30, 60, 90, and 150 degrees s-1) and isometric (knee-joint
      angle approximately equal to 60 degrees) muscle actions. Maximal angular velocity
      was determined during unloaded knee extensions. RESULTS: N2O decreased peak
      torque at any given angular velocity. The overall decrease in peak averaged 4.8
      +/- 2.2% (P < 0.0001). Likewise, N2O decreased maximal angular velocity by 5.7 +/
      4.3% (P < 0.01). Thus, the impairment in muscle function induced by a 35% N2O is
      only minute and hence most likely of little significance in clinical practice.

PMID- 8738696
TI  - Lung uptake of lidocaine during hyperoxia and hypoxia in the dog.
AB  - BACKGROUND: Lidocaine has been shown to accumulate in the lung following its
      administration. This study was undertaken to determine effects of dose of
      lidocaine on lung uptake during hyperoxic and hypoxic ventilation. METHODS: Using
      cross-circulation of ventilation and constant-flow perfusion of the left lower
      lobe independently from all other lobes of the dog lung under nitrous oxide and
      halothane anesthesia, lidocaine was infused into the inflow system, so that
      plasma lidocaine concentrations in the inflow blood were maintained at 5, 10, 20,
      40 and 70 micrograms/ml respectively during ventilation with 50% O2 or 3% O2.
      During 20 micrograms/ml lidocaine infusion, indocyanine green (ICG), an
      intravascular marker, was mixed with the lidocaine solution, in such a fashion
      that plasma ICG concentration in the inflow blood was maintained at 20
      micrograms/ml. Actual plasma lidocaine and ICG concentrations in blood drawn from
      the inflow ([Lid]pa,[ICG]pa) and the outflow ([Lid]pv,[ICG]pv)systems were
      measured, 1, 3, 5, 7 and 10 minutes after the beginning of lidocaine infusion.
      Percent lung uptake of perfused lidocaine was calculated as ?1
      ([Lid]pv/[Lid]pa)/([ICG]pv/[ICG]pa)? x 100. RESULTS: During ventilation
      hyperoxia, mean percent lung uptakes of lidocaine were 41-52% 1 minute after the
      beginning of lidocaine infusion, and decreased in time-dependent fashion to 7-12%
      10 minutes later. Curves of percent lung uptake of lidocaine over time were
      similar for the 5 predetermined lidocaine concentration groups (5-70
      micrograms/ml). There were no significant differences in percent lung uptakes of
      lidocaine between the ventilation hyperoxia and hypoxia conditions. CONCLUSIONS:
      These findings suggest that percent lung uptake of lidocaine is unaffected by
      hypoxic ventilation and by varying the concentration of lidocaine in the
      perfusion through the recipient dog lung lobe.

PMID- 8738697
TI  - Cytokines in stored red blood cell concentrates: promoters of systemic
      inflammation and simulators of acute transfusion reactions?
AB  - BACKGROUND: The cytokine network has important implications for the systemic
      inflammatory and metabolic response in trauma and infection. Cytokines
      exogenously administered to traumatized and infected patients may have
      implications for the trauma response in these patients. The main objective of
      this study was to characterize red blood cell concentrates (RBCs) with regard to
      cytokine content. METHODS: We investigated the concentrations of tumor necrosis
      factor alpha (TNF), interleukin-1 beta (IL-1), interleukin-6 (IL-6) and
      interleukin-8 (IL-8) in sixteen units of RBCs stored at +4 degrees C during 40
      days. Samples from RBCs were taken every tenth day. Healthy volunteers were used
      as controls. RESULTS: IL-1 and IL-8 in RBCs were increased compared to controls,
      P < 0.01 - P < 0.001 and TNF in RBCs were increased on days 1 and 40 compared to
      controls, P < 0.05. During storage TNF was highest on day 1, 69 (< 3-1060) pg/ml,
      median (range). IL-1 concentrations increased during the period of storage from 5
      (< 2 - 205) pg/ml to 174 (< 2 - 2180) pg/ml, P < 0.01. IL-6 was 6 (< 2 - 210)
      pg/ml on day 1 and did not change over the period of storage. IL-8 was highest on
      day 40, 164 (15 - 790) pg/ml and compared to day 1 the concentrations were
      increased on day 10 and day 40, P < 0.05 for both comparisons. CONCLUSIONS: The
      results indicate the presence of TNF, IL-1, IL-6 and IL-8 in stored RBCs, though
      there was a great variability over the period of storage and between units of
      RBCs. In some samples of RBCs the content of cytokines reached levels that may be
      anticipated to contribute to systemic inflammation and the symptomatology of
      acute transfusion reactions.

PMID- 8738698
TI  - Left ventricular rupture following external chest compression.
AB  - A case of a 62-year-old woman suffering an acute cardiac arrest during a court
      dispute is presented. Cardiopulmonary resuscitation was immediately started by
      bystanders. In hospital there were signs of intrathoracic bleeding. A left
      thoracotomy revealed a cardiac rupture of the left ventricle and a large
      pericardial tear. Intraoperative evaluation of the heart as well as postoperative
      enzyme levels and ECG did not indicate acute myocardial infarction. The rupture
      may therefore be traumatic. The cardiac rupture was sutured five hours after the
      initial resuscitation, and the patient discharged from the intensive care unit
      two days after the rupture without clinical signs of neurological injury. A
      precordial thump is advised before start of external chest compression. One
      beneficial effect may be that the ventricles empty and the risk of traumatic
      rupture during compression is reduced.

PMID- 8738699
TI  - Epidural injection of potassium hydrochloride.

PMID- 8738700
TI  - The ultrastructure of parapapillary chorioretinal atrophy in eyes with secondary
      angle closure glaucoma.
AB  - BACKGROUND: The present study was performed to investigate the ultrastructure of
      deep retinal layers and choroid corresponding to the parapapillary chorioretinal
      atrophy in eyes with secondary angle-closure glaucoma. METHODS: The glaucomatous
      eyes included two eyes enucleated due to iris ring melanoma with high intraocular
      pressure and one eye with neovascular glaucoma enucleated due to ocular pain. The
      control eyes included one eye enucleated due to choroidal malignant melanoma with
      normal intraocular pressure and one eye enucleated during surgery for
      supramandibular carcinoma. These eyes were studied with light and electron
      microscopy. RESULTS: In the region of parapapillary chorioretinal atrophy of
      glaucomatous eyes, the retinal pigment epithelial cells showed degenerative
      changes, such as loss of basal infoldings and microvilli, degenerated
      mitochondria, vacuolar degeneration and irregular distribution of melanin
      granules. The photoreceptors were decreased in number in this area of
      glaucomatous eyes. The lumen of the choriocapillary vessels adjacent to the optic
      nerve was collapsed. CONCLUSION: These results elucidate the fine structures of
      deep retina and choroid in the region of parapapillary chorioretinal atrophy of
      glaucomatous eyes, and suggest that the reduced choroidal perfusion might be the
      pathogenetic mechanism of glaucomatous parapapillary chorioretinal atrophy.

PMID- 8738701
TI  - Vitiligo in Vogt-Koyanagi-Harada disease: immunohistological analysis of
      inflammatory site.
AB  - BACKGROUND: Vogt-Koyanagi-Harada disease (VKH) consists of uveitis with
      associated non-ocular symptoms, such as vitiligo or central nervous system
      disorders. A cell-mediated immune disorder is believed to play an important role
      in VKH; however, the skin lesion has not been well studied. Therefore, for this
      study, we examined the skin of a 56-year-old Japanese man with Vogt-Koyanagi
      Harada disease (VKH). METHODS: Skin biopsy specimens from the patient's vitiligo
      were obtained 1 month after the onset of ocular symptoms. Immunohistochemical
      analysis of the specimens study was performed using the following monoclonal
      antibodies: anti-T cell, anti-B cell, anti-major histocompatibility complex class
      II (HLA-DR), anti-T helper/inducer (CD4), and anti-T suppressor/ cytotoxic
      lymphocytes (CD8). RESULTS: Histopathologic analysis revealed mononuclear cell
      infiltration of the slightly edematous dermis, especially surrounding the hair
      follicles and sweat glands. Melaninladen cells in the epidermis were partially
      lost. The infiltrating mononuclear cells consisted primarily of T lymphocytes
      with a smaller number of B lymphocytes. Most showed expression of HLA-DR. CD4
      positive lymphocytes were dominant over CD8-positive cells (3:1). CONCLUSIONS:
      The results indicate that vitiligo of VKH is infiltrated by mostly activated
      helper/inducer lymphocytes and that cell-mediated immunity plays an important
      role in the pathogenesis of the dermal lesions of VKH as well.

PMID- 8738703
TI  - Head and eye movements in children with low vision.
AB  - BACKGROUND: Early childhood nystagmus may herald blindness, brain tumors, benign
      idiopathic motor nystagmus or spasmus nutans. Nystagmus unique to low vision was
      sought. METHODS: Videotapes and head/ eye movements of 18 congenitally visually
      impaired subjects were analyzed. RESULTS: Nystagmus of congenitally visually
      impaired subjects was characterized as small horizontal or vertical movements
      superimposed on larger oscillations. Small and large nystagmus movements were of
      pendular or jerk type. Slow-phase jerk nystagmus had increasing, constant and
      decreasing velocities. Fast-phase nystagmus changed direction periodically.
      Pendular nystagmus was out of phase and evolved to jerk nystagmus in two
      subjects. All subjects displayed head nodding, and one stabilized gaze with head
      movements. CONCLUSION: Eye movement recordings allow characterization and
      differentiation of subjects with nystagmus and low vision from other nystagmus
      forms.

PMID- 8738702
TI  - Histopathology of episcleral fibrosis after trabeculectomy with and without
      mitomycin C.
AB  - BACKGROUND: The aim of the study was to investigate the histopathologic features
      of scar tissue which have proliferated at the site of trabeculectomy of surgical
      failures after procedures with and without the use of the antimetabolite
      mitomycin C (MMC). METHODS: We obtained seven surgical specimens after
      trabeculectomy without MMC and five specimens after trabeculectomy with MMC,
      which were compared with 23 controls. Sections were stained with hematoxylin and
      eosin, Verhoeff-van Gieson, Grocott methenamine silver, and alcian blue. An
      immunohistochemical stain was performed for alpha-smooth muscle actin. RESULTS:
      Specimens from eyes operated without MMC showed dense scar tissue with many
      fibroblasts, much ground substance, parallel-oriented collagen fibers, and
      contractile intracellular proteins within the fibroblasts. Specimens from eyes
      operated with MMC consisted of tissue with only few fibroblasts which did not
      exhibit contractile proteins. Collagen fibers were arranged randomly with less
      ground substance. CONCLUSION: Even after 1-10 months, the scar tissue was
      distinctly different in the two groups. These results suggest that the use of MMC
      has long-term effects in vivo. Surgical failures related to scar formation are
      possible and not reduced to zero.

PMID- 8738704
TI  - Chloroquine-induced lipidosis in the rat retina: functional and morphological
      changes after withdrawal of the drug.
AB  - BACKGROUND: The antimalarial and antirheumatic drug chloroquine is one of the
      most infamous amphiphilic cationic drugs in clinical ophthalmology. It is known
      to cause lipidosis and photoreceptor degeneration in the human and the rat
      retina. METHODS: We treated female albino Wistar rats (mean weight 200 g) orally
      with chloroquine (95 mg/kg body weight) for 12 weeks, followed by a period of 4
      months with normal feed. After initial electroretinography in all rats,
      measurements were made after 4 and 12 weeks of treatment and 16 weeks after
      withdrawal. The rats were prepared for histological examination. RESULTS:
      Treatment of rats with chloroquine caused severe lipidosis in the neuroretina;
      photoreceptor cell degeneration was slight. After 12 weeks of treatment, the b
      wave amplitude was reduced to 30% of the initial value; the a-wave amplitude was
      reduced, but remained within the range of normal values. After withdrawal of
      chloroquine the lipidosis remitted, but the degeneration of the photoreceptor
      cell layer continued to progress. Despite remission of lipidosis,
      electroretinography demonstrated functional disturbances, marked by reduction of
      the a- and b-wave amplitudes to 25% and 16% of initial values, respectively.
      CONCLUSIONS: Seen from the point of view of function, it is doubtful whether
      lipidosis is the primary cause of changes in the electroretinogram or of receptor
      cell degeneration.

PMID- 8738705
TI  - The role of cell adhesion molecules in allograft rejection after penetrating
      keratoplasty in mice. Clinical and immunohistochemical study.
AB  - BACKGROUND: It has been reported that adhesion molecules play an important role
      in immunological rejection after organ transplantation. In the present study, we
      examined the role of ICAM-1/ LFA-1 adhesion molecules in corneal allograft
      rejection and evaluated the immunological specificity of monoclonal antibodies
      (mAbs) in preventing allograft rejection in mice. METHODS: The allografted mice
      were intraperitoneally injected with 100 micrograms/day of the following mAbs: a
      control mAb, anti-ICAM-1 mAb, anti-LFA-1 mAb, or a mixture of anti-ICAM-1 and
      anti-LFA-1 mAbs from 1 day before to 7 days after surgery. The expression of ICAM
      1 and LFA-1 molecules in the grafted cornea was studied immunohistochemically.
      The corneas from a syngeneic donor or a third-party strain were transplanted 4
      weeks after the initial keratoplasty onto the mice treated with both anti-ICAM-1
      and anti-LFA-1 mAbs. RESULTS: The allografts treated with anti-LFA-1 mAb alone or
      both anti-ICAM-1 and anti-LFA-1 mAbs remained transparent for more than 2 weeks,
      and the survival rate at 8 weeks was 40% in both groups. ICAM-1 was expressed on
      the mononuclear cells, keratocytes and endothelial cells in the allografts
      without treatment. The second corneal grafts syngeneic to the initial donor
      remained transparent at 2 weeks, whereas those from the third party were
      rejected. CONCLUSIONS: ICAM-1 and LFA-1 adhesion molecules play a crucial role in
      the pathophysiology of corneal transplant rejection. The immunosuppressive
      effects of anti-ICAM-1 and anti-LFA-1 mAbs are highly allospecific. The
      administration of mAbs to the adhesion molecules represents a new means of
      suppressing allograft rejection after penetrating keratoplasty.

PMID- 8738706
TI  - Retinopathy in diabetic hypertensive monkeys: a pathologic study.
AB  - BACKGROUND: No satisfactory primate model of diabetic retinopathy has been
      produced. The clinical picture of microangiopathic retinopathy in diabetic
      hypertensive monkeys has been previously reported. The present study describes
      the pathologic findings of these animals. METHODS: Eleven eyes of six monkeys
      (five rhesus, one cynomolgus) were studied. Diabetes mellitus was either
      spontaneous or induced by streptozocin; mild arterial hypertension was either
      spontaneous or induced by fludrocortisone acetate. In two monkeys, the
      horseradish peroxidase tracer technique was employed. Trypsin flat preparations
      of the nasal retinal vasculature were prepared. The material was studied by light
      and electron microscopy. RESULTS: We divided the development of the
      microangiopathic retinopathy into three stages. In the early stage, background
      retinopathy was characterized by microvascular abnormalities and capillary
      dropout. Massive vascular leakage, intraretinal exudates and hemorrhage, cystoid
      degeneration, and cotton-wool spots were features of an exudative retinopathy in
      the second stage. In the final stage, chronic ischemic retinopathy was
      characterized by vascular occlusions and areas of retinal atrophy. CONCLUSION:
      Microangiopathic retinopathy in diabetic monkeys with mild hypertension presented
      many features of human diabetic and hypertensive retinopathy, except vitreous
      neovascularization.

PMID- 8738707
TI  - A standardized classification of ocular trauma.
AB  - BACKGROUND: No internationally standardized classification of ocular trauma
      terminology has existed heretofore. Despite a growing interest in eye injuries,
      the absence of a common language continues to impede both clinical care and
      research. METHODS: A classification was initially developed based on the authors'
      extensive personal experience. It then under-went repeated reviews over a 3-year
      period by international ophthalmic specialists. Written and oral suggestions from
      respondents in 19 countries and from selected ocular trauma experts were
      considered and incorporated. RESULTS: By always using the entire globe as the
      tissue of reference, the new classification is unambiguous, consistent, simple,
      and comprehensive. It provides definitions for the terms commonly used in eye
      trauma and creates a logical system of injury types. CONCLUSION: In addition to
      widespread international acceptance by professionals, the new classification has
      been endorsed by the International Society of Ocular Trauma, the United States
      Eye Injury Registry, the American Academy of Ophthalmology, the Hungarian Eye
      injury Registry, the Vetreous Society, and the Retina Society. It can be
      reasonably expected that the system will ultimately become the standardized
      international language of ocular trauma.

PMID- 8738708
TI  - Ophthalmological and neuro-ophthalmological involvement in Churg-Strauss
      syndrome: a case report.
AB  - BACKGROUND: It is well known that different types of eye involvement may develop
      during the course of systemic vasculitides. METHODS: We report here a case of
      Churg-Strauss syndrome (allergic granulomatous angiitis) characterized by the
      presence of multiple ophthalmological and neuro-ophthalmological lesions, i.e.,
      mononeuritis of the fourth cranial nerve, multifocal choroidal ischaemia, and
      bilateral ischaemic optic neuropathy. RESULTS: Ischaemic lesions in the posterior
      ciliary plexus and chorio-retinal circulation, which appeared simultaneously
      after a phase of disease activity, were documented. CONCLUSION: The simultaneous
      occurrence of multiple ocular features in a patient with Churg-Strauss syndrome
      suggests that regional vasculitis may be the pathological mechanism underlying
      the multiple ophthalmological lesions in this disorder.

PMID- 8738709
TI  - Communication between the subretinal space and the vitreous cavity in the morning
      glory syndrome.

PMID- 8738710
TI  - Photocarcinogenesis.

PMID- 8738711
TI  - Bullous pemphigoid possibly induced by psoralen plus ultraviolet A therapy.
AB  - An elderly white man with a long history of psoriasis, previously treated with
      topical steroids and ultraviolet B (UVB), developed bullous pemphigoid shortly
      after starting psoralen plus UVA (PUVA) therapy. The eruption spread from the
      forearms to the arms and neck after phototherapy was discontinued. The clinical
      features of the 12 reported cases of PUVA-induced bullous pemphigoid are
      reviewed.

PMID- 8738712
TI  - Skin response to ultraviolet B light in patients infected with human
      immunodeficiency virus.
AB  - Photosensitivity disorders have been reported in human immunodeficiency virus
      (HIV)-infected patients, often as the initial manifestation of the disease. The
      objective of this study was to evaluate whether the HIV-infected population
      demonstrates increased sensitivity to ultraviolet B (UVB) radiation. Minimal
      erythema dose values to UVB (MED-B) of 57 consecutive HIV-infected patients were
      compared to those of a control group of 57 consecutive patients with skin
      diseases, who were otherwise healthy and had no risk factors for HIV infection.
      MED-B determinations were performed in all individuals prior to the initiation of
      phototherapy for treatment of skin disease. None of the patients had a history of
      photosensitivity. Furthermore, the mean levels of the highest UVB doses received
      by each group during the treatment courses were compared. The mean age of the HIV
      infected cohort was 43 years (range 26-61 years). The mean MED-B for this group
      was 82.8 +/- 3.8 (SEM) mJ/cm2. The mean age of the control group was 45 years
      (range 24-77 years), and their mean MED-B was 81.0 +/- 3.8 (SEM) mJ/cm2. After 12
      weeks of treatment, one HIV-infected patient developed photosensitivity
      associated with a decreased MED-B value. The mean level of the highest UVB doses
      received by the HIV-infected group [427.5 +/- 67.2 (SEM) mJ/cm2] was lower than
      that received by the control group [640.8 +/- 65.9 (SEM) mJ/cm2], since HIV
      infected patients received fewer treatments (mean: 34.7 treatments per patient)
      than the patients in the control group (mean: 65.6 treatments per patient). These
      data indicate that the HIV-infected patient population, without history of
      photosensitivity, does not show increased sensitivity to UVB light as determined
      by MED-B values.

PMID- 8738713
TI  - Effects of ultraviolet A and antioxidant defense in cultured fibroblasts and
      keratinocytes.
AB  - Lipid peroxidation, measured by the thiobarbituric acid-reactive substances
      assay, was evaluated for cultured human skin fibroblasts and keratinocytes
      exposed to ultraviolet A radiation (320-400 nm, UVA). Peroxidation increases with
      increasing UVA doses and is much lower for keratinocytes than for fibroblasts.
      Immediate UVA-induced cytotoxicity, monitored by the trypan blue exclusion assay,
      is also lower for keratinocytes. Thus, cultured human skin keratinocytes are less
      sensitive than fibroblasts to the immediate deleterious effects of UVA with
      respect to membrane damage and lipid peroxidation. As a first attempt to
      understand this lower sensitivity of keratinocytes, basal levels of antioxidant
      defenses including total glutathione, superoxide dismutase, glutathione
      peroxidase and catalase were evaluated in both keratinocytes and fibroblasts from
      the same donors. We failed to correlate this lower susceptibility of keratinocyte
      to UVA-induced lipid peroxidation and cytotoxicity with a higher antioxidant
      status.

PMID- 8738714
TI  - Relationship between skin color and cutaneous response to ultraviolet radiation
      in Thai.
AB  - Predictors of sensitivity to ultraviolet (UV) light, including Fitzpatrick's sun
      reactive skin types, constitutive skin color and facultative skin color were
      assessed in 43 healthy Thai volunteers. These predictors were compared with one
      another and with responses of the skin to UV irradiation, as determined by a
      minimal erythema dose (MED) of UVB, a minimal immediate pigment darkening dose
      (MIPDD) of UVA, and a minimal delayed tanning dose (MDTD) of UVA, and by dose
      response curves for erythema and pigmentation, as measured objectively with the
      use of a narrow-band spectrophotometer. The skin type did not correspond well to
      the constitutive and facultative skin color. There was no correlation between
      skin type and MED and no relation between skin type and the slope of the dose
      response curves for erythema and pigmentation. Constitutional skin color was also
      not a good predictor of the measured MED, MIPDD and MDTD values but did appear to
      correlate with the steepness of the dose-response curves for erythema but not for
      pigmentation. The facultative skin color, however, did not correlate with the
      dose-response angle of erythema or pigmentation. We have thus found that the skin
      type is not a good predictor of UV responses in Thai. The constitutive skin color
      is a better predictor of UV responses of the skin than skin type and that
      steepness of dose-response curves for erythema is a better measure of the
      response of the skin to UV irradiation than is a MED measurement.

PMID- 8738715
TI  - Treatment with topical khellin in combination with ultraviolet A or solar
      simulated radiation is carcinogenic to lightly pigmented hairless mice.
AB  - Khellin is used together with either UVA irradiation or sun exposure in the
      treatment of vitiligo. The purpose of this study was to investigate the
      carcinogenic effect of topically applied khellin together with UVA or solar
      simulated radiation (SSR) in lightly pigmented C3H/Tif mice. For comparison
      purposes a 0.1% 8-methoxypsoralen (8-MOP) cream was also tested in combination
      with SSR. Fifty microliters of a 5% khellin cream, a 0.1% 8-MOP cream, or a cream
      without active substances were spread uniformly on the back of the mice 30
      minutes before UVA or SSR irradiation. All mice were irradiated 3 times a week
      until age or skin tumor development necessitated killing. Treatment with topical
      khellin and UVA irradiation was carcinogenic to lightly pigmented hairless mice,
      time to 50% of the mice had developed one tumor (t50) was 507 days. This
      indicates that the combination of topical khellin and UVA radiation, formerly
      expected to be rather innocuous, is carcinogenic to mice. Also the combination of
      khellin and SSR (t50 = 268 days) enhanced skin tumor development significantly
      compared with control cream and SSR (t50 = 330 days), P < 0.05. In addition, the
      combination of khellin and SSR was found to have the same carcinogenic effect as
      treatment with 0.1% 8-MOP and SSR (t50 = 262 days). This study shows that
      topically applied khellin increases the carcinogenic effect of both UVA and
      sunlight.

PMID- 8738716
TI  - Contact allergy to 3-(4' methylbenzylidene) camphor and contact and photocontact
      allergy to 4-isopropyl dibenzoylmethane.
AB  - We report a clinical case of a 15-year-old boy who presented a photodistributed
      eruption after having used a sunscreen cream for 8 days. Photobiological testing
      showed a contact allergy to 3-(4' methylbenzylidene) camphor (Eusolex 6300)
      included in his sunscreen cream associated with a contact and photocontact
      allergy to 4-isopropyl-dibenzoylmethane (Eusolex 8020) not included.

PMID- 8738717
TI  - Photoprotection due to pigmentation and epidermal thickness after repeated
      exposure to ultraviolet light and psoralen plus ultraviolet A therapy.
AB  - Tanning and thickening of the epidermis are cardinal defensive responses of human
      skin to ultraviolet (UV) radiation that lead to increased photoprotection.
      Earlier studies have shown that skin pigmentation can be used to predict minimal
      erythema dose and minimal phototoxic dose. In this study it was calculated how
      much of the increase in photoprotection after 4 weeks of repeated exposure to
      suberythemogenic doses of either UVA or UVB radiation sources or psoralen plus
      UVA (PUVA) therapy that was attributable to melanogenesis. The backs of 12
      volunteers were exposed to 6 different UVA and UVB radiation sources 9 times
      during 4 weeks. Skin pigmentation was assessed by skin reflectance measuring.
      Photoprotection was determined from the minimal erythema dose. Melanogenesis
      accounted for 63-95% of the increase in photoprotection after 4 weeks of exposure
      to UVA radiation. Exposure to two UVB sources induced a significant increase in
      photoprotection but not in pigmentation. Melanogenesis accounted only for 6-11%
      of the increase in photoprotection after 4 weeks of UVB exposure. The pigmentary
      and photoprotective responses to PUVA therapy were followed in 14 patients. After
      2 weeks of exposure, the increase in photoprotection was significantly higher
      than predicted from the increase in skin pigmentation. After 4 weeks,
      melanogenesis accounted for only 36% of the increase in photoprotection. This
      study shows that melanogenesis accounts for the increased photoprotection after 2
      weeks of exposure to UVA radiation, but after 4 weeks other protective mechanisms
      occur. During suberythemal UVB exposure and during PUVA therapy the importance of
      skin pigmentation in the overall photoprotection gradually decreases during a 4
      week irradiation period.

PMID- 8738718
TI  - The human leucocyte antigen (HLA) DR expression and the distribution of T
      lymphocytes in the fimbriae of the normal fallopian tube and during pelvic
      adhesion disease.
AB  - PROBLEM: Systematically to investigate the expression of human leucocyte antigen
      (HLA) DR on the columnar epithelium and the content of T-lymphocytes in the
      fimbriae specimens of the fallopian tube from healthy women and from women with
      infertility and pelvic adhesions. METHOD: The staining of HLA-DR expression on
      the columnar epithelium was judged on a four-graded scale according to the
      distribution of HLA-DR expression. The amount and distribution of T-lymphocytes
      were registered. RESULTS: The biopsies from normal fimbriae contained sparsely
      infiltrating T-lymphocytes. On the columnar epithelial cells a patchy HLA-DR
      expression was observed that was more widespread in preovulatory cases. In some
      biopsies from sactosalpinx, the HLA-DR expression was found completely to cover
      the columnar epithelial cells and was associated with a heavy infiltration of T
      lymphocytes. CD4+ T-lymphocytes dominated in all but one adhesion biopsies.
      CONCLUSION: The findings indicate an ongoing immunological activity in pelvic
      adhesions that might immunologically influence fertility.

PMID- 8738719
TI  - Expression of gamma delta T cells and adhesion molecules in endometriotic tissue
      in patients with endometriosis and adenomyosis.
AB  - PROBLEM: Are T cell subsets including gamma delta T cells. HLA antigens or
      adhesion molecules, expressed in eutopic and ectopic endometria in patients with
      endometriosis and adenomyosis? METHODS: Subjects consisted of 23 patients with
      adenomyosis and 21 patients with endometriosis. Controls consisted of 15 patients
      with adenomyoma and 42 infertile women without habitual abortion and autoimmune
      diseases. Staining of the glandular cells in eutopic and ectopic endometria or T
      lymphocyte subsets or macrophages in the stroma were analyzed
      immunohistochemically to localize the expression of the antigens. RESULTS:
      Immunohistochemical analysis revealed significantly increased expression of the
      antigens, particularly of the number of gamma delta T cells in the stroma and
      adhesion molecules and HLA antigens on the glandular cells in eutopic and ectopic
      endometria, compared with materials from patients with adenomyoma and infertile
      patients. CONCLUSION: It is likely that three distinct pathways of cell-cell
      interactions are activated in patients with endometriosis or adenomyosis.

PMID- 8738720
TI  - Antibodies to endometrial transferrin and alpha 2-Heremans Schmidt (HS)
      glycoprotein in patients with endometriosis.
AB  - PROBLEM: Identifying the endometrial antigens inciting autoimmunity is important
      in setting up an antibody assay for a non-invasive diagnosis and clinical
      monitoring of endometriosis. METHODS: Two-dimensional gel electrophoresis of
      endometrial extracts, Western blot analysis, passive hemagglutination and enzyme
      linked immunosorbent assay (ELISA), amino acid sequencing and molecular studies
      were done on chosen antigens. Forty-six women with endometriosis, 4 women with
      uterine leiomyomata, 4 with pelvic adhesions, 3 with repeat Cesarean sections
      (conditions that coexist with or predispose to endometriosis) and 46 controls
      participated. RESULTS: Antigens with molecular weights (MW) of 64 kDa
      [isoelectric point (pI) of 3.5-4.0] and 72 kDa (pI of 4.5) bound to IgG in all
      patients with endometriosis, but not the controls. Amino acid sequencing of the
      proteins revealed that they had homology to alpha 2-Heremans Schmidt (HS)
      glycoprotein (MW: 64 kDa) and transferrin (MW: 72 kDa). Endometriosis patients
      had significant antibody levels to these two proteins (predictive value of 80
      90%). The analysis of patients' endometrial RNA detected the message for alpha 2
      HS glycoprotein and transferrin. Albumin (pI 5.5) and collagen (pI 3.5) failed to
      elicit antibody responses. CONCLUSIONS: Patients with endometriosis have
      significant antibodies to endometrial transferrin and alpha 2-HS-glycoprotein. We
      can effectively use an antibody assay using these antigens for diagnosing
      endometriosis.

PMID- 8738721
TI  - Implication of abnormal human trophoblast karyotype for the evidence-based
      approach to the understanding, investigation, and treatment of recurrent
      spontaneous abortion. The Recurrent Miscarriage Immunotherapy Trialists Group.

PMID- 8738722
TI  - Serum levels of interleukin-8 in alcoholic liver disease: relationship with
      disease stage, biochemical parameters and survival.
AB  - BACKGROUND/AIMS: Interleukin-8 (IL-8), a cytokine produced by a host of cells,
      including monocytes, macrophages, Kupffer cells and hepatocytes, can activate
      neutrophils. Peripheral neutrophilia and liver neutrophil infiltration are
      frequently noted in patients with alcoholic liver disease. However, the
      relationship between IL-8 and different stages of alcoholic liver disease is
      uncertain. The aim of this study is to determine if a correlation exists between
      circulating IL-8 levels and biochemical and histological parameters and survival
      in alcoholic liver disease. METHODS: Serum levels of IL-8 were determined with an
      enzyme-linked immunosorbent assay in 166 subjects, consisting of 30 healthy
      controls, 26 patients with non-alcoholic fatty liver, 15 with alcoholic fatty
      liver, 32 with alcoholic hepatitis, 30 with alcoholic cirrhosis, 28 with chronic
      hepatitis B and 5 with chronic hepatitis C. RESULTS: Serum IL-8 levels were
      markedly elevated in patients with alcoholic hepatitis (437 +/- 51 pg/ml) when
      compared with all other groups (p < 0.05). Levels of IL-8 in patients with
      alcoholic fatty liver, alcoholic cirrhosis and viral hepatitis were higher than
      those in controls and in patients with non-alcoholic fatty liver. In addition, IL
      8 levels were higher in patients who died (p = 0.007), and correlated with
      biochemical and histological parameters, and severity of liver injury: serum
      aspartate aminotransferase, alanine aminotransferase, total bilirubin,
      prothrombin time, indocyanine green retention ratio, tumor necrosis factor-alpha
      and peripheral neutrophil count in patients with alcoholic hepatitis. After a 2
      year follow up, patients with IL-8 above 479 pg/ml had a higher mortality rate in
      the alcoholic hepatitis group (p = 0.033). CONCLUSIONS: These findings suggest
      that IL-8 is activated in alcoholic liver disease, especially in alcoholic
      hepatitis, and is closely correlated with liver injury. IL-8 levels can reflect
      the stage and severity of alcoholic liver disease, and may serve as a predictor
      of survival in patients with alcoholic hepatitis.

PMID- 8738723
TI  - Hepatocyte proliferation and serum hepatocyte growth factor levels in patients
      with alcoholic hepatitis.
AB  - BACKGROUND/METHODS: Hepatocyte growth factor is thought to be important in
      stimulating growth of the liver following injury. In this study we have measured
      serum levels of hepatocyte growth factor together with hepatocyte proliferation
      in liver biopsies, by detection of the Ki-67 antigen, in 23 patients with
      alcoholic hepatitis. RESULTS: Serum hepatocyte growth factor was elevated in all
      patients (median 0.9 ng/ml; range 0.6-7.7 ng/ml; normal < 0.5 ng/ml) and there
      was a positive correlation between hepatocyte growth factor levels and hepatocyte
      proliferation in the biopsies. CONCLUSIONS: These results demonstrate that in
      acute alcoholic hepatitis the liver proliferates in response to injury and
      suggest that hepatocyte growth factor may be one of the growth factors
      responsible for this proliferative activity.

PMID- 8738724
TI  - Efficacy of low-dose alpha interferon therapy in HBV-related chronic liver
      disease in Asian Indians: a randomized controlled trial.
AB  - BACKGROUND/AIMS: Interferon therapy has been shown to be effective in Western
      patients with chronic hepatitis due to hepatitis B viral infection, but not in
      Asian Chinese. Its efficacy in Asian Indian subjects with chronic HBV infection
      is not known. METHODS: Forty-one patients with HBV-related chronic liver disease
      received randomly either: (a) recombinant alpha 2b interferon (n = 20) 3 MIU,
      subcutaneously, three times a week for 4 months, or (b) no treatment (n = 21).
      Patients were followed up for 12 months after completion of therapy. RESULTS: In
      the interferon-treated group, complete response (loss of HBV-DNA and HBeAg) was
      significantly higher than spontaneous clearance in the control group (50% vs.
      4.8% p < 0.05). Seroconversion to anti-HBe was seen in 35% of the treated and
      4.8% of the control group (p < 0.05) at 4 months; it was noticeably higher in
      patients with chronic hepatitis than in those with cirrhosis. In the responders,
      alanine aminotransferase levels nearly normalized. One year after interferon
      therapy, HBeAg and HBV-DNA clearance was observed in 65% of patients, with HBsAg
      clearance in 15%. Reactivation was not seen in any patient. Side-effects were
      transient and minimal. CONCLUSION: Low-dose recombinant alpha interferon therapy
      is quite effective and safe in Asian Indians with chronic liver disease due to
      hepatitis B infection.

PMID- 8738725
TI  - Hepatitis C virus antibody, viral RNA and genotypes in leprous patients in Japan.
AB  - BACKGROUND/METHODS: Markers of hepatitis C virus infection were tested for in 229
      patients with leprosy (male 154, female 75) in Japan. RESULTS: Antibody to
      hepatitis C virus by a second-generation enzyme immunoassay was detected in 68
      patients (30%), and RNA of hepatitis C virus in 41 (18%), in prevalence rates
      much higher (p < 0.001) than those in matched controls (11/923 or 1.2% and 9/923
      or 1.0%, respectively). Hepatitis C virus genotypes were II/1b in 37 (90%),
      III/2a in three (7%) and IV/2b in one (2%), in which II/1b was more frequently (p
      < 0.003) represented than in hepatitis C virus carriers without leprosy in Japan
      (520/767 or 68%). The 41 patients with hepatitis C virus viremia had serum
      transaminase levels significantly higher than those in the other 188 patients
      without viremia (p < 0.01). CONCLUSIONS: These results indicate that leprous
      patients confined in institutions are at high risk of hepatitis C virus
      infection, and that patients infected with hepatitis C virus should be monitored
      for liver function and placed on interferon therapy whenever required.

PMID- 8738726
TI  - Primary cultured normal human hepatocytes for hepatitis B virus receptor studies.
AB  - BACKGROUND/AIMS: We analyzed the hepatitis B virus envelope specificities (HBs,
      preS2 and preS1) involved in virus attachment to normal human hepatocytes, and we
      performed in vitro hepatitis B virus infection experiments without addition of
      dimethyl sulfoxide and polyethylene glycol, which may affect cell membrane
      integrity, in order to study further the early steps of the life cycle of the
      hepatitis B virus. METHODS: Primary normal human hepatocytes were prepared from
      surgical biopsies by the two-step collagenase perfusion technique, and cultured
      in a fetal calf serum-free medium supplemented with 10(-6) M dexamethasone. Cell
      binding assays, ligand blotting and immunohistochemistry experiments were carried
      out using our anti-idiotypic (Ab2) antibodies (Ab2s/preS1, Ab2s/preS2 and
      Ab2s/HBs). RESULTS: Probing primary normal human hepatocytes, the 35-kDa major
      preS1-binding protein (preS1-BP35) we have previously identified in human
      hepatoma HepG2 cells was recognized in blotting, whereas both HBs- and preS1
      specificities of the hepatitis B virus envelope interacted strongly with normal
      human hepatocyte cell membrane in cell-binding assays and immunohistochemistry
      experiments. Hepatitis B virus infectivity studies confirmed a great inter
      experimental variability depending on donors and liver perfusion, and
      demonstrated a great intra-experimental variability depending on the serum
      derived hepatitis B virus isolate used for the inoculation. In our culture
      conditions, only increased detection of the RC and CCC DNA forms of hepatitis B
      virus in cells and of hepatitis B virus surface antigens in medium was observed 4
      to 8 days after exposure of cells to hepatitis B virus. CONCLUSION: These
      findings support a potential role for preS1-BP35 as a receptor protein for
      hepatitis B virus. In our hands, limitation(s) in the hepatitis B virus life
      cycle may occur at some step after virion binding, and likely result from complex
      regulation of reverse transcription of the RNA and translation of core protein by
      extrahepatic host factors or/and by the virus itself. However, the normal human
      hepatocyte model developed here is available for studying the initial steps in
      hepatitis B virus entry into cells.

PMID- 8738727
TI  - A human combined hepatocellular and cholangiocarcinoma cell line (KMCH-2) that
      shows the features of hepatocellular carcinoma or cholangiocarcinoma under
      different growth conditions.
AB  - BACKGROUND/AIMS: Combined hepatocellular and cholangiocarcinoma is a rare tumor
      of the liver, and its histogenesis remains unclear. The authors addressed this
      issue in the current article. METHODS: A specimen aseptically obtained from the
      surgically resected combined hepatocellular and cholangiocarcinoma was processed
      for primary culture. The morphologic features of the established cell line
      cultured on a plastic dish and in type I collagen gel matrix, and transplanted in
      nude mice were examined. RESULTS: The authors established a new human combined
      hepatocellular and cholangiocarcinoma cell line, designated KMCH-2, from a 40
      year-old Japanese man. KMCH-2 cells on a plastic dish proliferated in a
      monolayered sheet with a population doubling time of 32 to 44 h. KMCH-2 expressed
      functional characteristics of hepatocellular carcinoma, such as albumin synthesis
      at protein and mRNA levels, but were poorly differentiated in morphology, showing
      an overlap of features with cholangiocarcinoma. KMCH-2 cells cultured within type
      I collagen gel matrix proliferated, forming compact to vaguely trabecular and
      pseudoglandular arrangements, and differentiated to show morphological
      characteristics of hepatocellular carcinoma unlike the cells on a plastic dish.
      Mucin production was not detected in KMCH-2 cells in vitro. Subcutaneous tumors
      which developed in nude mice injected with KMCH-2 cells represented features of
      adenocarcinoma with mucin production. CONCLUSIONS: The present results revealed
      the presence of an albumin-producing human hepatic neoplastic cell, such as KMCH
      2, that can differentiate to show not only the features of hepatocellular
      carcinoma but also those of cholangiocarcinoma under certain growth conditions.

PMID- 8738728
TI  - Effects of isosorbide-5-mononitrate on variceal pressure and systemic and
      splanchnic haemodynamics in patients with cirrhosis.
AB  - BACKGROUND: Isosorbide-5-mononitrate is a long-acting nitrovasodilator which was
      introduced for the treatment of portal hypertension because of its capacity to
      reduce portal pressure. In contrast to vasoconstrictors, isosorbide-5-mononitrate
      acts primarily by decreasing portal-collateral resistance without deleterious
      effects on liver function, although at high doses, a reflex splanchnic
      vasoconstriction elicited by the fall in arterial pressure may further decrease
      portal pressure. However, there is no information on the effects of isosorbide-5
      mononitrate on variceal pressure, which is thought to be a major determinant of
      variceal haemorrhage. METHODS: We investigated the effects of isosorbide-5
      mononitrate (40 mg, orally; n = 12) or placebo (n = 10) on variceal pressure (non
      invasive endoscopic gauge) and hepatic haemodynamics in 22 patients with
      cirrhosis. RESULTS: Placebo administration had no significant effects. In
      contrast, isosorbide-5-mononitrate significantly reduced variceal pressure (from
      13.5 +/- 3.6 to 9.8 +/- 3.2 mmHg, p < 0.005). This was associated with a fall in
      wedged hepatic venous pressure (from 28 +/- 5.8 to 25.9 +/- 6.2 mmHg, p < 0.005),
      hepatic venous pressure gradient (from 20 +/- 4 to 18 +/- 4.7 mmHg, p < 0.005)
      and azygos blood flow (from 668 +/- 197 to 597 +/- 160 ml/min, p < 0.05),
      suggesting that the decrease in variceal pressure caused by isosorbide-5
      mononitrate could be caused by both reductions in collateral resistance and
      collateral blood flow. Isosorbide-5-mononitrate moderately reduced mean arterial
      pressure (-13 +/- 16%; p < 0.005), its fall being directly related to the fall in
      hepatic venous pressure gradient (r = 0.6, p < 0.01). CONCLUSIONS: The results of
      this study show that isosorbide-5-mononitrate markedly and significantly reduces
      variceal pressure in patients with cirrhosis and provide further support for its
      clinical use in the pharmacological treatment of portal hypertension.

PMID- 8738730
TI  - Defective aggregation in cirrhosis is independent of in vivo platelet activation.
AB  - BACKGROUND/AIMS: Platelet function abnormalities contribute to the hemostatic
      defect in patients with cirrhosis. In this study we evaluated the occurrence of
      in vivo platelet activation as a possible mechanism of defective platelet
      aggregation in patients with cirrhosis. METHODS: Nine patients with severe (Child
      B-C) cirrhosis and defective platelet aggregation were studied in comparison with
      age- and sex-matched healthy controls. The presence of activated platelets in the
      bloodstream was evaluated by fluorescence-activated flow cytometry using
      antibodies directed against activation-dependent platelet proteins and by
      measuring plasma levels of beta-thromboglobulin and platelet factor 4. Urinary
      levels of 11-dehydro-TXB2 and of 2,3-dinor-TXB2 were assayed by radioimmunoassay
      following chromatographic separation. RESULTS: In unstimulated platelets, the
      expression of both GMP 140 and GP 53 was not significantly different in patients
      with cirrhosis and in controls. After stimulation with ADP and epinephrine,
      expression of activation-dependent antigens was lower in platelets from patients
      (GMP 140: 0.64 +/- 0.09 vs 0.73 +/- 0.04, p = 0.02; GP 53: 0.41 +/- 0.13 vs 0.54
      +/- 0.14). Plasma levels of beta-thromboglobulin and platelet factor 4, as
      indexes of in vivo platelet activation, were also comparable in the two groups of
      subjects. Urinary levels of 11-dehydro-TXB2 and of 2,3-dinor-TXB2, the major
      systemic metabolites of TXA2, were significantly higher in patients with
      cirrhosis (1807 +/- 518 vs 341 +/- 121 ng/pg creatinine and 693 +/- 512 vs 205
      (93 ng/pg creatinine, respectively, p < 0.001). However, increased excretion of
      TXB2 metabolites was also observed in three patients with chronic autoimmune
      thrombocytopenia. CONCLUSIONS: These data indicate that circulating platelets are
      not activated in cirrhosis, and that defective aggregation is most likely
      dependent on the alteration of the transmembrane signaling pathways. The
      increased urinary excretion of systemic TXA2 metabolites may be related to
      increased intrasplenic platelet destruction.

PMID- 8738729
TI  - Propranolol plus molsidomine vs propranolol alone in the treatment of portal
      hypertension in patients with cirrhosis.
AB  - BACKGROUND/AIMS: Effective protection from the risk of variceal bleeding is
      achieved when the hepatic venous pressure gradient is reduced to 12 mmHg or at
      least by 20% of baseline values. Such a marked decrease is rarely achieved with
      propranolol, and new agents or combinations of them are now being explored. The
      present randomized study investigated whether chronic treatment with the
      combination of propranolol plus molsidomine, a preferential venous dialator that
      reduces hepatic venous pressure gradient and does not cause pharmacological
      tolerance, achieves greater reduction in hepatic venous pressure gradient than
      propranolol alone. METHODS: A hemodynamic study was performed in 34 patients with
      cirrhosis with portal hypertension in baseline conditions and after 3 months of
      chronic oral treatment with propranolol alone (n = 19) or propranolol plus
      molsidomine (n = 15). RESULTS: Propranolol produced a significant reduction in
      hepatic venous pressure gradient (-16%, p < 0.01). Propranolol plus molsidomine
      also caused a slight but significant decrease in hepatic venous pressure gradient
      (-9%, p < 0.05). Hepatic blood flow and the hepatic and intrinsic clearance of
      indocyanine green were significantly reduced by propranolol. The combined
      administration of propranolol+molsidomine significantly reduced hepatic blood
      flow but not hepatic and intrinsic clearance of indocyanine green. Both treatment
      groups produced similar reduction in azygos blood flow, heart rate and cardiac
      output. However, contrary to propranolol alone, propranolol plus molsidomine did
      not increase cardiopulmonary pressures. CONCLUSIONS: The current study shows that
      although the combined administration of propranolol plus molsidomine prevents
      some of the adverse effects of propranolol on liver function and cardiopulmonary
      pressures, it does not achieve a greater reduction in hepatic venous pressure
      gradient than propranolol alone and therefore, does not support the use of this
      combined therapy for the pharmacological treatment of portal hypertension.

PMID- 8738731
TI  - The metabolism of cholestanol in primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: The concentration of serum cholestanol, a 5 alpha-saturated
      derivative of cholesterol, is increased in primary biliary cirrhosis
      proportionally to impaired liver function for unknown reasons. The purpose of
      this study was to analyze serum cholestanol level and its biliary and fecal
      elimination, and relate the results to cholesterol absorption and metabolism.
      METHODS: Sixteen patients with primary biliary cirrhosis and 44 non-primary
      biliary cirrhosis controls were studied. Squalene and non-cholesterol sterols
      were analyzed by gas-liquid chromatography, cholesterol absorption by the peroral
      double-isotope continuous feeding method, and neutral and acidic sterols in bile
      and feces by gas-liquid chromatography. RESULTS: In primary biliary cirrhosis,
      the mean level of serum cholesterol was normal, but the cholestanol/cholesterol
      proportion was increased 4-fold, and the proportion was related to the serum bile
      acid and bilirubin levels. The mean biliary cholestanol proportion and the
      biliary secretion rate were increased 5- and 2-fold, respectively, suggesting
      that at low cholestanol absorption cholestanol synthesis was increased.
      Calculated clearance of serum cholestanol into bile was decreased. The fecal
      output was within the control limits, so that intestinal cholestanol production
      was lowered in primary biliary cirrhosis. In addition, serum and biliary plant
      sterol proportions were increased in primary biliary cirrhosis, but their biliary
      secretion was unchanged, while those of cholesterol, bile acids, phospholipids,
      and cholesterol precursor sterols were markedly reduced. CONCLUSIONS: We conclude
      that an enhanced cholestanol synthesis and a cholestasis-induced decrease in
      biliary clearance of serum cholestanol contribute to the excessively high serum
      cholestanol level in primary biliary cirrhosis. In addition, reduced bile acid
      synthesis may contribute to the increased serum cholestanol content.

PMID- 8738732
TI  - Influence of anti-HLA antibodies and positive T-lymphocytotoxic crossmatch on
      survival and graft rejection in human liver transplantation.
AB  - BACKGROUND/AIMS: The role of crossmatching in liver transplantation is
      controversial. The aim of this study was to investigate retrospectively the
      effect of sensitization and IgG lymphocytotoxic crossmatching on liver
      transplantation. METHODS/RESULTS: Over 5 years, 20 of 243 (8.2%) first liver
      transplants were performed with a positive crossmatch and their outcome was
      compared with the remaining 223 performed with a negative crossmatch. Women had a
      higher incidence of positive crossmatch than men (p < 0.001). Significant
      differences in mean panel reactive antibody of 2.7% and 43.3% were found in
      negative and positive crossmatch patients, respectively (p < 0.001). Severe early
      rejection resulting in graft loss occurred in eight of 20 positive crossmatch
      patients, and only one of 223 negative crossmatch patients (p < 0.001). Five of
      the remaining positive crossmatch patients suffered several acute rejection
      episodes some months after liver transplantation. Two of 20 in the positive
      crossmatch group developed chronic rejection (10%) compared with ten of 223
      negatives (4.4%) (N.S). Nine of 16 positive crossmatch female recipients suffered
      graft loss and seven died, representing 1-year graft and patient survival of 56%
      and 43%, respectively. Fifteen of 68 negative crossmatch female recipients
      presented graft loss and 12 died, accounting for 1-year patient and graft
      survival of 82% and 78% (p < 0.005), respectively. Five patients (20%) displayed
      positive crossmatch at the time of retransplantation, compared with 24 (10%) who
      were negative (N.S). CONCLUSION: Our experience confirms the adverse impact of a
      positive crossmatch in liver transplantation, particularly in female recipients.
      Candidates with high panel reactive antibody are more likely to display a
      positive crossmatch, and therefore to develop early severe rejection and graft
      failure.

PMID- 8738733
TI  - Intracellular calcium concentration impairment in hepatocytes from thioacetamide
      treated rats. Implications for the activity of Ca(2+)-dependent enzymes.
AB  - METHODS/RESULTS: Thioacetamide induced a severe perivenous necrosis followed by a
      hepatocellular regenerative response, when administered in a single dose of 6.6
      mmol/kg to rats. As (Ca2+)i plays an important role in both toxic cell killing
      and cell proliferation, the disturbances in the basal cytosolic calcium as well
      as the levels of Ca2+ sequestered in the endoplasmic reticulum were determined in
      hepatocytes isolated at 0, 12, 24, 48 and 72 h after thioacetamide
      administration. The basal Ca2+ increased progressively, reaching a maximum at 24
      h of the intoxication (205%, p < 0.001), while the microsomal sequestered Ca2+
      decreased at 24 h to 16% (p < 0.001) when compared with untreated controls.
      Changes in the activity of glycogen phosphorylase alpha paralleled those of basal
      free calcium and showed the maximum value also at 24 h (291%; p < 0.001).
      Moreover, there was a close association in time between the basal concentration
      of Ca2+ and the inhibition of microsomal Ca(2+)-dependent ATPase activity.
      CONCLUSIONS: The significant decrease in the levels of GSH and protein thiols
      indicates that oxidative stress is involved in thioacetamide-induced cell injury,
      but these decreases did not precede changes in cytosolic Ca2+ level. In the
      sequence of events leading to hepatic cell injury and regeneration, thioacetamide
      mobilized hepatic (Ca2+)i via inhibition of microsomal Ca(2+)-ATPase which may
      have activated Ca(2+)-dependent mechanisms involved both in cell death and in
      acute mitogen response.

PMID- 8738735
TI  - Renal vasoactive mediator generation in portal hypertensive and bile duct ligated
      rats.
AB  - BACKGROUND/METHODS: Vasoactive substances may have a role in the pathogenesis of
      functional renal abnormalities in patients with cirrhosis. We determined renal
      vasoactive mediators in rats with portal hypertension since the balance in each
      part of the kidney between the vasodilator activity of prostaglandin E2 and the
      vasospastic activity of thromboxane A2, leukotriene B4, leukotriene C4,
      endothelin-1 and platelet activating factor may determine renal function. Rats
      with partial portal vein ligation (n = 7), complete bile duct ligation (n = 6)
      and sham operated (n = 10) were studied. Three weeks following surgery renal
      function tests, including fractional excretion of sodium [Fe(Na)] were measured.
      Rats were anesthetized, splenic pulp pressure was measured, kidneys were removed,
      and cortex, medulla and papilla were separated and homogenized for determination
      of prostaglandin E2, thromboxane B2, leukotriene B4, leukotriene C4 and
      endothelin-1 by radioimmunoassay (ng/g) and platelet activating factor activity
      (pg/10 mg) by platelet aggregation. RESULTS: Pulp pressure was > 13 mmHg in
      portal vein ligated and bile duct ligated and 6 mmHg in sham operated rats. In
      bile duct ligated rats there was a 70% decrease in Fe(Na) and a significant
      decrease in cortical and papillary prostaglandin E2, whereas cortical thromboxane
      B2 and platelet activating factor activity in the cortex, medulla and papilla
      were double that of sham operated rats. A similar but insignificant trend of
      changes was found in portal vein ligated rats. Medullary leukotriene B4 was
      significantly decreased in bile duct ligated rats. Papillary leukotriene B4 was
      not detected in bile duct ligated and portal vein ligated rats. Renal leukotriene
      C4 generation in the three groups was either unchanged (papilla) or beyond
      detection (cortex and medulla). Medullary and papillary endothelin-1 in portal
      vein ligated and bile duct ligated rats were 178%-130% higher than in sham
      operated rats. A significant negative correlation was found between Fe(Na) and
      cortical and medullary thromboxane B2 generation and medullary platelet
      activating factor activity. CONCLUSIONS: 1) In bile duct ligated rats enhanced
      intrarenal generation of thromboxane A2 and platelet activating factor may
      contribute to decreased renal sodium excretion. 2) The role of decreased
      intrarenal prostaglandin E2 and increased intrarenal endothelin-1 content in bile
      duct ligated rats is not yet understood. 3) Renal leukotriene generation is
      either decreased or undetected in portal vein ligated and bile duct ligated rats.

PMID- 8738734
TI  - Phagocytic function and metabolite production in thioacetamide-induced liver
      cirrhosis: a comparative study in perfused livers and cultured Kupffer cells.
AB  - BACKGROUND/AIMS: The aim of the study presented here was to evaluate the basal
      and stimulated phagocytic activities and the metabolite production of isolated
      perfused livers, and also the phagocytic capacity of cultured Kupffer cells from
      rats with macronodular cirrhosis. METHODS: Rats were made cirrhotic by oral
      administration of thioacetamide. The phagocytic activity was assessed by the rate
      of removal of colloidal carbon. The Kupffer cells were prepared by a
      pronase/collagenase digestion method followed by elutriation. RESULTS: The
      phagocytic activity and production of glucose, lactate and pyruvate were reduced
      in cirrhotic livers when calculated per g liver. Due to hyperplastic-regenerative
      processes the mass of the cirrhotic livers was markedly augmented so that the
      colloidal carbon uptake calculated per cirrhotic liver was not significantly
      different from the controls. Colloidal carbon-induced glucose release increased
      more markedly in the controls than in cirrhotic livers. Isoproterenol
      considerably stimulated phagocytosis and glucose production in controls, whereas
      the response was clearly reduced in cirrhotic livers when calculated either per g
      liver or per total liver weight. The cyclic AMP analogue elicited a marked
      glycogenolytic response in the controls, whereas there was only a slight increase
      in glucose production in cirrhotic livers. Phagocytosis of cirrhotic livers was
      only moderately stimulated by opsonized zymosan when compared with the controls.
      Freshly isolated Kupffer cells exhibited a reduced phagocytic activity.
      Stimulation by zymosan was observed only in cell suspensions of the controls. In
      contrast, Kupffer cells from cirrhotic livers did not differ from controls with
      respect to basal or zymosan-stimulated phagocytic activity after 48-h
      cultivation. CONCLUSION: The stimulated phagocytic function was disturbed in
      perfused macronodular-cirrhotic livers as compared to controls. In contrast, 48-h
      cultured Kupffer cells from cirrhotic livers exhibited the same basal and
      stimulated phagocytic capacity as controls. The glucose release from perfused
      livers, initiated by stimulation of Kupffer cells or hepatocytes, was
      significantly reduced in cirrhotic livers. Therefore, we postulate an impaired
      intra- and/or intercellular signalling in macronodular-cirrhotic livers.

PMID- 8738736
TI  - Hyporeactivity of mesenteric resistance arteries in portal hypertensive rats.
AB  - BACKGROUND/AIMS: Hyporesponsiveness to vasoconstrictors in portal hypertension
      has been shown to involve increased production of nitric oxide in large arteries
      in vitro. Small arteries (diameter 50-500 microns) are partly responsible for
      peripheral resistance and probably have different regulatory mechanisms from
      large arteries. The purpose of this study was to investigate the hyporeactivity
      of small mesenteric resistance arteries in portal hypertensive rats and to
      determine the role of nitric oxide and prostaglandins in this hyporesponsiveness.
      METHODS: Third branch mesenteric arteries from normal and portal hypertensive
      rats obtained by portal vein ligation were isolated and suspended in myographs
      for isometric tension recording. Reactivity to vasoconstrictors was assessed by
      dose-responses to phenylephrine (Phe 10(-8) to 10(-3) M) and by potassium
      chloride (KCl 45 mM). Acetylcholine (Ach 10(-5) M) was administered in pre
      contracted KCl 45 mM arterial rings to evaluate endothelium-dependent relaxation.
      Pre-incubations with N-nitro-L-arginine (L-NNA 10(-4) M, a specific inhibitor of
      nitric oxide synthase, or with indomethacin (10(-5) M), a specific inhibitor of
      cyclo-oxygenase, were performed to compare the individual roles of nitric oxide
      and prostaglandins in KCl 45 mM-induced contractions. RESULTS: Impaired responses
      to Phe (3731 +/- 851 microN and 5971 +/- 745 microN, respectively; p < 0.05) and
      to KCl (2197 +/- 251 vs 2804 +/- 222 microN, respectively; p < 0.05) were
      observed in mesenteric resistance arterial rings from portal hypertensive rats
      compared to rings from normal rats. Ach-dependent relaxation did not
      significantly differ between normal (-25.7 +/- 5.1%) and portal hypertensive (
      17.3 +/- 3.3%) rats. Indomethacin induced a similar significant increase in KCl
      induced contraction in normal (3472 +/- 400 microN) and portal hypertensive (3432
      +/- 654 rats. Nitric oxide synthesis inhibition had no effect in normal rats
      (3032 +/- 368 microN) but significantly increased KCl-induced contraction in
      portal hypertensive rats (3331 +/- 551 microN). CONCLUSION: These results
      demonstrate the existence of a hyporesponsiveness to vasoconstrictors in small
      mesenteric resistance arteries of portal hypertensive rats, which seems to be due
      to increased production of nitric oxide.

PMID- 8738737
TI  - A reevaluation of the association of hepatitis C virus replicative intermediates
      with peripheral blood cells including granulocytes by a tagged reverse
      transcription/polymerase chain reaction technique.
AB  - BACKGROUND/AIMS: Persistence of hepatitis C virus at extrahepatic sites is of
      both basic and clinical interest. The clinical interest arises mainly from the
      occurrence of reinfections of the hepatic allograft following transplantation.
      Therefore, any extrahepatic association of virus, e.g. with peripheral blood
      cells, appears relevant. METHODS: In this study we employed for the first time
      the recently developed tagged reverse transcription/polymerase chain reaction
      procedure to determine the presence of genomic HCV RNA and antigenomic
      replicative intermediates in RNA preparations from sera, peripheral blood
      mononuclear cells, and polymorphonuclear granulocytes of 29 patients with chronic
      hepatitis C virus infection. RESULTS: All sera were found to contain both genomic
      and antigenomic HCV RNA. In addition to peripheral blood mononuclear cells, viral
      nucleic acids were found to be associated with polymorphonuclear granulocytes,
      too. CONCLUSIONS: In individual patients different patterns were observed for the
      distribution of hepatitis C virus genomes and antigenomes among peripheral blood
      mononuclear cells and polymorphonuclear granulocytes, apparently neither related
      to pretreatment biochemical parameters, nor to response following interferon
      alpha 2a treatment, nor to hepatitis C virus genotype.

PMID- 8738738
TI  - Differential expression of Na+,H(+)-antiporter mRNA in biliary epithelial cells
      and in hepatocytes.
AB  - BACKGROUND/AIMS: Amiloride inhibitable Na+,H(+)-exchange has recently been
      identified and characterized in rat biliary epithelial cells where its activity
      at low intracellular pH is significantly higher than in hepatocytes. METHODS:
      Northern blot and reverse transcription-polymerase chain reaction were used to
      study the expression of the different Na+,H(+)-antiporter isoforms in isolated
      biliary epithelial cells and hepatocytes. RESULTS: The present study demonstrates
      for the first time the expression of Na+,H(+)-antiporter isoform 1 mRNA in rat
      biliary epithelial cells. Moreover, steady-state levels of this message were
      several-fold higher in biliary epithelial cells than in hepatocytes. In addition,
      the expression of Na+,H(+)-antiporter isoform 2 in bile duct epithelial cell but
      not hepatocytes could be demonstrated by reverse transcription-polymerase chain
      reaction. CONCLUSIONS: The higher expression of Na+,H(+)-antiporter isoform 1
      mRNA may indicate a higher rate of synthesis and therefore a higher Na+,H(+)
      exchange activity in biliary epithelial cells than in hepatocytes and is entirely
      compatible with the results of the previous functional studies.

PMID- 8738739
TI  - Immunosuppression after liver transplantation.

PMID- 8738740
TI  - Aquaretic agents: a new potential treatment of dilutional hyponatremia in
      cirrhosis.
AB  - An impairment in the renal capacity to excrete water is a common finding in
      patients with cirrhosis and ascites. In some patients this abnormality is minor
      since it is only detectable by measuring urine volume or free water clearance
      after a water load and is not associated with changes in plasma osmolality and
      serum sodium concentration. In other patients the intensity of the disorder is
      such that they are not able to eliminate their regular water intake, and develop
      dilutional hyponatremia and hypoosmolality. The renal capacity to excrete water
      is one of the most useful prognostic indicators in patients with cirrhosis and
      ascites. The main pathogenic factors of the impaired water excretion in human
      cirrhosis are an increased plasma concentration of AVP, a reduced renal synthesis
      of prostaglandins and a reduced delivery of filtrate to the ascending limb of the
      loop of Henle. At present, no effective therapy exists for the management of this
      complication. Two types of drugs have recently been reported that selectively
      increase renal water excretion, antagonists of the AVP V2 receptors and kappa
      opioid agonists. Experimental studies have shown that both substances improve
      water excretion in rats with cirrhosis and ascites. Therefore, these drugs may
      represent a novel therapeutic tool in the management of spontaneous hyponatremia
      in cirrhosis and in the treatment or prevention of diuretic-induced hyponatremia
      in these patients.

PMID- 8738741
TI  - Anti-actin autoantibodies in patients with chronic hepatitis C.

PMID- 8738742
TI  - Gay and lesbian identity development: a social identity perspective.
AB  - This paper critically examines models of identity development from the
      perspective of social identity theory. It is argued that recent perspectives on
      homosexual identity development have focused upon psychological processes of the
      individual and that a shift toward a more social psychological perspective is
      required. Extant models of homosexual identity development and associated
      relevant evidence are described, and criticisms of these models are discussed.
      Next, social identity theory is outlined, illustrating how such an approach can
      address the criticisms of the dominant approach to gay and lesbian identity
      development. An extension of social identity theory is then offered in an attempt
      to explain some of the identities which homosexuals have developed in reaction to
      being members of an oppressed group.

PMID- 8738743
TI  - Sampling homosexuals, bisexuals, gays, and lesbians for public health research: a
      review of the literature from 1990 to 1992.
AB  - Our objective was to examine the representativeness of samples of homosexuals,
      bisexuals, gays, and lesbians obtained for public health research. We identified
      journal articles cited in Medline and published between 1990 and 1992 that
      sampled individuals and classified them as homosexual, bisexual, gay, and/or
      lesbian. Information was abstracted from these articles to evaluate four
      components of sample selection affecting the representativeness of samples: (1)
      how the population is conceptually defined, (2) how the sampled population is
      operationally identified, (3) the setting from which samples are selected, and
      (4) the use of probability sampling to select subjects. We identified 152 public
      health articles published between 1990 and 1992 that sampled homosexuals,
      bisexuals, gays, and/or lesbians. We found articles (1) rarely (4/152)
      conceptually defined the population they were sampling, (2) used a range of
      incomparable methods to identify and select subjects, (3) sampled from settings
      representative of dramatically different populations, and (4) rarely (3/152) used
      probability sampling. Overall, we find methods used to identify homosexuals,
      bisexuals, gays, and lesbians for public health research produce samples
      representative of different and sometimes unidentifiable populations. To
      understand these populations from a public health perspective, it is imperative
      that steps be taken by researchers to standardize population definitions and
      sampling methodologies.

PMID- 8738744
TI  - Assessment of sexual orientation in lesbian/gay/bisexual studies.
AB  - This article provides a critical review of various methods for assessing sexual
      orientation in previous lesbian/gay/bisexual studies. A content analysis of 144
      lesbian/gay/bisexual studies published in the Journal of Homosexuality (Volumes 1
      to 24; 1974-93) was conducted by two independent reviewers. Findings suggest that
      women and bisexuals were underrepresented, and, in about one third of the
      studies, participants' sexual orientations were assumed rather than assessed.
      Five methods for the assessment of sexual orientation were identified, with self
      identification (as heterosexual/homosexual/bisexual/lesbian/gay) the most
      typical. Each assessment method was critically examined and a 2-by-2
      multidimensional assessment model was suggested for use in lesbian/gay/bisexual
      studies.

PMID- 8738745
TI  - The attitudes of undergraduate college students toward gay parenting.
AB  - A sample of undergraduate college students from a large midwestern university (N
      = 97) read one of four vignettes describing a couple interested in adopting a
      five-year-old African-American male child. Participants completed questionnaires
      that assessed their reactions to the couple described in the vignette. The
      vignettes were identical except that the couples' ethnicity was either African
      American, Caucasian, or inter-racial (i.e., African-American and Caucasian) or
      their sexual orientation was either homosexual or heterosexual. Results indicate
      that subjects who rated the homosexual couple were more likely to view them as
      creating a dangerous environment for the child, to create a more insecure home,
      to be more emotionally unstable, and to be less likely to be awarded custody of
      the child than the heterosexual couples. Participants who were more theistic,
      irrationally worried, and tense were more likely to hold negative attitudes
      toward the gay couple. Recommendations for promoting attitude change toward
      gay/lesbian parenting is also presented.

PMID- 8738746
TI  - A needs analysis of Brisbane lesbians: implications for the lesbian community.
AB  - This study examined the needs of lesbians in Brisbane, a state capital city of
      Australia, and the importance of lesbian "community" in meeting those needs. The
      extent to which a lesbian community can meet the needs of individual lesbians is
      dependent on what those needs are, the prevailing social climate, and the
      resulting degree of access by lesbians to the community. This study examined
      lesbians' perceptions of their individual needs and the extent to which they
      looked to their community to meet those needs. Overall, the results indicated
      that lesbians in Brisbane had many unmet needs which, in many instances, cut
      across the demographic spectrum of age, politics, stage of identity development,
      religious beliefs, occupation, and educational achievements. These can be broadly
      categorized as needs that related to the lesbian community itself and external
      needs that related to changes needed in heterosexual society. The results of this
      study indicated that characteristics of community do exist within the Brisbane
      lesbian subculture. There were distinct, identifiable, interacting small groups
      and social networks in existence. However, a common need was for an identifiable,
      accessible, lesbian community that could provide stable, long-term services and
      cultural and social activities. In Brisbane lesbians also needed a focus that
      superseded the needs of individual lesbians and their small interacting social
      networks. This study highlighted the need for further research into the area of
      lesbian community identity formation.

PMID- 8738747
TI  - Who is the male homosexual? A computer-mediated exploratory study of gay male
      Bulletin Board System (BBS) users in New York City.
AB  - Using simple computer technology, 290 male homosexual Bulletin Board System (BBS)
      users in the greater New York City area participated in a study, the objective
      results of which are presented here as information of potential importance and/or
      interest to social workers, psychologists, and related mental health
      professionals. While, in general, members of the population studied tend to look
      like everyone else, some interesting differences with respect to (1) health
      related concerns and behaviors, (2) educational attainment, and (3) socio
      emotional characteristics (measured by computer administration and scoring of the
      Myers-Briggs Type Indicator) were identified and are presented and discussed.
      Further work relative to the latter is both urged and anticipated in the mental
      health professions' continuing efforts to operationalize their shared concerns
      about and values related to diversity.

PMID- 8738748
TI  - Regional differences in gene expression for calcium activated neutral proteases
      (calpains) and their endogenous inhibitor calpastatin in mouse brain and spinal
      cord.
AB  - The family of calpains (CANP or calcium activated neutral proteases) and their
      endogenous inhibitor calpastatin have been implicated in many neural functions;
      however, functional distinctions between the major calpain isoforms, calpain I
      and II, have not been clearly established. In the present study we analyzed the
      gene expression patterns for calpain I and II and calpastatin in mouse brain and
      spinal cord by measuring both their mRNA and protein levels. Our results show
      that the overall mRNA level measured by competitive reverse transcription
      polymerase chain reaction for calpain II is 15-fold higher and for calpastatin is
      three-fold higher than that for calpain I. Overall, both mRNA and protein
      expression levels for the calpains and calpastatin showed no significant
      difference between the spinal cord and the brain. The cellular distributions of
      mRNA for calpain I or calpastatin, measured by in situ hybridization, are
      relatively uniform throughout the brain. In contrast, calpain II gene expression
      is selectively higher in certain neuron populations including pyramidal neurons
      of the hippocampus and the deep neocortical layers, Purkinje cells of cerebellum,
      and motor neurons of the spinal cord. The motor neurons were the most enriched in
      calpain message. Motor neurons possessed 10-fold more calpain II mRNA than any
      other spinal cord cell type. The differential distribution of the two proteases
      in the brain and the spinal cord at the mRNA level indicates that the two calpain
      genes are differentially regulated, suggesting that they play different
      physiological roles in neuronal activities and that they may participate in the
      pathogenesis of certain regional neurological degenerative diseases.

PMID- 8738749
TI  - Vasopressin and developmental onset of flank marking behavior in golden hamsters.
AB  - Golden hamsters start displaying flank marking behavior (a form of scent marking)
      around postnatal day 20 (P-20). Because the behavior is dependent upon the
      central activity of arginine vasopressin (AVP), the present study was conducted
      to correlate this activation with changes in the vasopressinergic system. A first
      set of experiments was performed to compare flank marking activity between P-18
      and P-22. A second set of experiments was performed to compare the density of AVP
      receptors between the age periods and assess responsiveness to AVP
      microinjection. Finally, a third set of experiments incorporated
      immunocytochemistry, radioimmunoassay, in situ hybridization, and Northern blot
      analysis to determine the location and numbers of AVP immunoreactive neurons and
      the level of mRNA correlating with the developmental onset of flank marking
      behavior. Our results show that flank marking develops between P-18 and P-22.
      Male and female hamsters do not display odor-induced flank marking anytime before
      P-19. However, all animals show odor-induced flank marking by P-22. The onset of
      flank marking does not appear to be associated with any change in AVP receptor
      binding in the anterior hypothalamus. Indeed, flank marking can be triggered in
      hamsters on P-18 by the microinjection of AVP in the anterior hypothalamus. This
      would suggest that the postsynaptic mechanisms contributing to the transduction
      of the AVP signal and the motor control of flank marking are intact prior to the
      onset of odor-induced flank marking. In contrast, AVP levels in the hypothalamus
      and pituitary increase by two to threefold between P-18 and P-22, suggesting that
      changes in AVP synthesis and release from presynaptic sites may contribute to the
      onset of flank marking. Interestingly, there is no change in AVP mRNA between P
      18 and P-22, which raises questions about posttranslational processing during
      this developmental period. These results suggest that heightened synthesis and
      release of AVP between P-18 and P-22 may contribute to the developmental onset of
      flank marking.

PMID- 8738750
TI  - Differential regulation of choline acetyltransferase expression in adult
      Drosophila melanogaster brain.
AB  - Choline acetyltransferase (ChAT,E.C.2.3.1.6) catalyzes the synthesis of
      acetylcholine, and is considered to be a phenotypic marker specific for
      cholinergic neurons. In situ hybridization using a nonradioactive cRNA probe
      identified a large number of cell bodies expressing ChAT mRNA in the cortices of
      wild-type Drosophila melanogaster brain. Strong labeling is remarkable in the
      cortical regions associated with the lamina and antennal lobe, and also in the
      median neurosecretory (MNS) cells within pars intercerebralis, suggesting that
      some of the lamina monopolar neurons, antennal interneurons, and MNS cells are
      cholinergic. In two temperature-sensitive mutant alleles, Chats1 and Chats2, most
      hybridization signal disappears after exposure to a restrictive temperature (30
      degrees C). Loss of signal is especially evident in the optic lobes. Some
      centrally located neurons, however, continue to express ChAT mRNA and are thus
      likely to have expression controlled in a different way than the majority of
      cholinergic neurons. Immunocytochemistry, using a ChAT specific monoclonal
      antibody, identified two sets of paired neurons located in the posterior cortex
      of the brain. These neurons persist in ChAT immunoreactivity even in the Chats
      mutants exposed to restrictive temperature. ChAT mRNA is also detectable in the
      corresponding cell bodies when Chats mutants are held at restrictive temperature.
      Our findings demonstrate some specific cholinergic neurons in Drosophila brain,
      and indicate that ChAT expression is differentially regulated in particular sets
      of cholinergic neurons.

PMID- 8738751
TI  - Growth, proliferation, and cell death in the ontogeny of transient DRG (Froriep's
      ganglia) of chick embryos.
AB  - A striking example of axial patterning in nervous system development is the
      unusual fate of dorsal root ganglia (DRG) that develop in the most rostral
      somites, the Froriep's ganglia. In amniotes, the DRG that develop adjacent to the
      occipital (cranial) and the first cervical segments of the CNS "disappear" early
      in embryonic development. In contrast, all other DRG are present throughout the
      animal's life. We here reexamine in greater detail the ontogeny of the longest
      surviving Froriep's ganglion of the chick embryo, DRG C-2. By 50 h of development
      (stage, st. 15), an anlagen of a DRG had formed in C-2 that was indistinguishable
      from those of adjacent "permanent" ganglia. At st. 18 [embryonic day (E) 2.5+],
      the C-2 DRG had the same shape and volume as permanent ganglia C-5 and C-6. C-2's
      development first diverged from that of normal DRG at st. 19 (E3-), when C-2 was
      observed to be half the size and shaped differently from its neighbors, and its
      peripheral nerve root began to degenerate. Two cellular mechanisms appear to
      contribute to the reduced size of C-2 compared to normal DRG at st. 20 at this
      early stage: lower proliferation and higher apoptosis rates. One-third fewer C-2
      cells were found to be in the S phase when compared to neighboring ganglia, and
      apoptotic cells were more than three times more abundant in C-2 than in
      conventional DRG at this stage. The C-2 DRG continued to grow, but at a slower
      pace than neighboring ganglia through st. 32 (E7). At the height of the normal
      programmed DRG cell death in normal cervical DRG at st. 28 (E6), even more
      massive apoptosis occurred in C-2, which resulted in the absence of this ganglion
      in 80% of st. 36 (E10) embryos. A recent study demonstrated that the
      overexpression of a single Hox gene can "rescue" the C-2 DRG in transgenic mice.
      We speculate that Hox genes may produce the difference in fate between C-2 and
      normal DRG by modulating proliferation and apoptosis via modified neurotrophic
      factor and/or receptor expression.

PMID- 8738752
TI  - Motor stereotypy and diversity in songs of mimic thrushes.
AB  - The relationship between the motor and acoustic similarity of song was examined
      in brown thrashers (Toxostoma rufum) and grey catbirds (Dumetella carolinensis)
      (family Mimidae), which have very large song repertoires and sometimes mimic
      other species. Motor similarity was assessed by cross correlation of syringeal
      airflows and air sac pressures that accompany sound production. Although most
      syllables were sung only once in the song analyzed, some were repeated, either
      immediately forming a couplet, or after a period of intervening song, as a
      distant repetition. Both couplets and distant repetitions are produced by
      distinctive, stereotyped motor patterns. Their motor similarity does not decrease
      as the time interval between repetitions increases, suggesting that repeated
      syllables are stored in memory as fixed motor programs. The acoustic similarity
      between nonrepeated syllables, as indicated by correlation of their spectrograms,
      has a significant positive correlation with their motor similarity. This
      correlation is weak, however, suggesting that there is no simple linear
      relationship between motor action and acoustic output and that similar sounds may
      sometimes be produced by different motor mechanisms. When compared without regard
      to the sequence in which they are sung, syllables paired for maximum spectral
      similarity form a continuum with repeated syllables in terms of their acoustic
      and motor similarity. The prominence of couplets in the "syntax" of normal song
      is enhanced by the dissimilarity of successive nonrepeated syllables that make up
      the remainder of the song.

PMID- 8738753
TI  - Neurotrophic effects of BDNF and CNTF, alone and in combination, on postnatal day
      5 rat acoustic ganglion neurons.
AB  - The neuronal survival promoting ability of brain derived neurotrophic factor
      (BDNF), and ciliary neurotrophic factor (CNTF), individually and in combination,
      was evaluated in dissociated cell cultures of postnatal day 5 (P5) rat acoustic
      ganglia. The neuritogenic promoting effect of these same neurotrophic factors was
      examined in organotypic explants of P5 rat acoustic ganglia. The results showed
      that BDNF was maximally effective at a concentration of 10 ng/mL in promoting
      both survival and neuritogenesis of these postnatal auditory neurons in vitro.
      CNTF was maximally effective at a concentration of 0.01 ng/mL at promoting both
      survival and neuritogenesis in the acoustic ganglion cultures. BDNF had its
      strongest effect on neuronal survival while CNTF was most effective in
      stimulating neurite outgrowth. These two neurotrophic factors, when added
      together at their respective maximally effective concentrations, behave in an
      additive manner for promoting both survival and neuritic outgrowth by the
      auditory neurons.

PMID- 8738754
TI  - Prevention of activity-dependent neuronal death: vasoactive intestinal
      polypeptide stimulates astrocytes to secrete the thrombin-inhibiting neurotrophic
      serpin, protease nexin I.
AB  - Neuronal cell death occurs as a programmed, naturally occurring mechanism and is
      the primary regressive event in central nervous system development. Death of
      neurons also occurs on an injury-induced basis after trauma and in human
      neurodegenerative diseases. Classical neurotrophic factors can reverse this
      phenomenon in experimental models prompting initiation of clinical trials in
      conditions such as amyotrophic lateral sclerosis and Alzheimer's disease. The
      glial-derived protease nexin I (PNI), a known promoter of neurite outgrowth in
      cell culture and a potent inhibitor of serine proteases, also enhances neuronal
      cell survival. PNI, in nanomolar concentrations, rescues spinal cord motor
      neurons from both naturally-occurring programmed cell death in the chick embryo
      as well as following injury in the neonatal mouse. The potent neuromodulator,
      vasoactive intestinal polypeptide (VIP), influences neuronal survival through
      glial-mediated factors and also induces secretion of newly synthesized astrocyte
      PNI. We now report that subnanomolar amounts of PNI enhance neuronal survival in
      mixed spinal cord cell culture, especially when neuronal cells were made
      electrically silent by administration of tetrodotoxin. The mediation of this
      effect is by inhibition of the multifunctional serine protease, thrombin, because
      hirudin, a thrombin-specific inhibitor, has the same effect. In addition, spinal
      cord neurons are exquisitely sensitive to thrombin because picomolar and lower
      levels of the coagulation factor causes neuronal death. Thus, PNI is an astrocyte
      derived, thrombin-inhibiting, activity-dependent neurotrophic agent, enhanced
      secretion of which by VIP may be one approach to treat neurological disorders.

PMID- 8738755
TI  - Transforming growth factor-alpha and other growth factors stimulate cell division
      in olfactory epithelium in vitro.
AB  - The rate of cell division in olfactory epithelium (OE) is upregulated by ablation
      of the olfactory bulb (Carr and Farbman, 1992), or downregulated by occlusion of
      a naris. We used an organ culture assay of fetal rat olfactory mucosa to study
      regulation of the mitotic rate. Addition of any one of three members of the
      epidermal growth factor (EGF) family-EGF, transforming growth factor-alpha (TGF
      alpha), or amphiregulin (AR)-to a serum-free culture medium resulted in a two- to
      threefold increase in the number of dividing OE cells. TGF-alpha elicited a
      maximal response in a dose of 100-200 pM culture medium and was 2 orders of
      magnitude more potent than the other EGF family members. Addition of TGF-beta 1,
      TGF-beta 2, insulinlike growth factor-1 or platelet-derived growth factor to the
      culture medium had slightly less effect than EGF or AR, in about the same molar
      dose range; addition of nerve growth factor had virtually no net effect on cell
      division. Immunohistochemistry on adult rat OE showed that basal cells,
      supporting cells, and acinar cells of Bowman's glands were immunoreactive with
      antibody to TGF-alpha but not with antibody to EGF. Most growth factors
      upregulated division of both olfactory neuron progenitors and supporting cells.
      The data suggest that several growth factors, most prominently TGF-alpha 1, may
      participate in the mitotic regulation of OE.

PMID- 8738756
TI  - Antibody that neutralizes myelin-associated inhibitors of axon growth does not
      interfere with recognition of target-specific guidance information by rat retinal
      axons.
AB  - During development, many CNS projection neurons establish topographically ordered
      maps in their target regions. Myelin-associated inhibitors of neurite growth
      contribute to the confinement of fiber tracts during development and limit
      plastic changes after CNS projections have been formed. Neutralization of myelin
      associated growth inhibitors leads to an expansion of the retinal innervation of
      the superior colliculus (SC). In the lesioned adult mammalian CNS, these long
      projection neurons are usually unable to regrow axons over long distances after
      lesion due to myelin-associated inhibitors, which interfere with axonal growth in
      vivo and in vitro. Application of a specific antibody directed against myelin
      inhibitors (IN-1) promotes regrowth of corticospinal tract or retinal ganglion
      cell axons. In the present study, we asked whether application of an antibody to
      myelin-associated growth inhibitors would lead to disturbances of target-specific
      axon guidance. To examine this issue, we used an in vitro model, the "stripe
      assay", to examine the behavior of rat retinal ganglion cell axons on membranes
      from embryonic and deafferented adult rat SC. On membrane preparations from
      embryonic rat SC, retinal fibers avoid posterior tectal membranes, possibly due
      to the presence of a repulsive factor. Nasal retinal axons show a random growth
      pattern. On membranes prepared from the deafferented adult rat SC, temporal and
      nasal axons prefer to grow on membranes prepared from their specific target
      region, which suggests the involvement of target-derived attractive guidance
      components. The results of the present study show that retinal axons grow
      significantly faster in the presence of IN-1 antibody that neutralizes myelin
      associated growth inhibitors present in the membrane preparations from the adult
      rat SC. IN-1 antibody, however, does not interfere with specific axonal guidance.
      This suggests that axonal guidance and specific target finding are independently
      regulated in retinal axons.

PMID- 8738757
TI  - Anti-agrin staining is absent at abandoned synaptic sites of frog neuromuscular
      junctions.
AB  - The neuromuscular junction is a plastic structure and is constantly undergoing
      changes as the nerve terminals that innervate the muscle fiber extend and retract
      their processes. In vivo observations on developing mouse neuromuscular junctions
      revealed that prior to the retraction of a nerve terminal the acetylcholine
      receptors (AChRs) under that nerve terminal disperse. Agrin is a protein released
      by nerve terminals that binds to synaptic basal lamina and directs the
      aggregation of AChRs and acetylcholinesterase (AChE) in and on the surface of the
      myotube. Thus, if the AChRs under a nerve terminal disperse, then the cellular
      signaling mechanism by which agrin maintains the aggregation of those AChRs, must
      have been disrupted. Two possibilities that could lead to the disruption of the
      agrin induced aggregation are that agrin is present at the synaptic basal lamina
      but is unable to direct the aggregation of AChRs, or that agrin has been removed
      from the synaptic basal lamina. Thus, if agrin were blocked, one would expect to
      see anti-agrin staining at abandoned synaptic sites; whereas if agrin were
      removed, anti-agrin staining would be absent at abandoned synaptic sites. We find
      that anti-agrin staining and alpha-bungarotoxin staining are absent at abandoned
      synaptic sites. Further, in vivo observations of retracting nerve terminals
      confirm that agrin is removed from the synaptic basal lamina within 7 days. Thus,
      while agrin will remain bound to synaptic basal lamina for months following
      denervation, it is removed within days following synaptic retraction.

PMID- 8738758
TI  - Nicotinic receptor subunits alpha 3, alpha 4, and beta 2 and high affinity
      nicotine binding sites are expressed by P19 embryonal cells.
AB  - Controlled exposure to retinoic acid (RA) induces the murine embryonal carcinoma
      cell line P19S18O1A1 (P19) to differentiate into a variety of cell types. One of
      the cell types exhibits neuronal-like morphology and expresses neuronal markers
      including neurofilament proteins, glutamate receptors, and the cholinergic
      enzymes choline acetyl-transferase and acetylcholinesterase. In this study we use
      Northern blot analysis, double-label immunocytochemistry, and single cell RNA
      analysis using polymerase chain reaction to show that RA-treated P19 cells with
      neuronal-like morphology also express neuronal nicotinic acetylcholine receptor
      (nAChR) subunits alpha 3, alpha 4, and beta 2. Greater than 80% of RA-treated P19
      cells with a neuronal-like phenotype express nAChR alpha 4 subunit transcripts
      and both alpha 4 and beta 2 protein. The RA-induced expression of alpha 3
      transcripts accounts for a comparably small number of nAChR-containing cells (<
      20%) of which half coexpress alpha 4 transcripts. Expression of high-levels of
      alpha 4 RNA is dependent upon both cell-cell contact and RA exposure. The
      appearance of nAChR subunits also coincides with RA-induced expression of high
      affinity [3H]-nicotine binding receptors. The P19 cell line offers an inducible
      neuronal cell system to study mammalian neuronal nicotinic receptor expression
      and the development of high affinity nicotinic binding sites similar to those
      expressed in the mammalian central nervous system.

PMID- 8738759
TI  - Stereoselective pharmacokinetics of methadone in chronic pain patients.
AB  - Ten patients with chronic pain were randomized to an open, balanced, crossover
      study. Each patients received two different preparations of racemic methadone,
      i.e., tablets and intravenous infusion. The pharmacokinetic parameters of the R-
      and S-enantiomers of the racemate are reported. The analgesically active R
      methadone has a significantly longer mean elimination half-life than the optical
      antipode S-methadone (t1/2 = 37.5 and 28.6 h, respectively). The mean total
      volume of distribution is 496.6 L for R-methadone and 289.1 L for S-methadone.
      Significant differences in the mean clearance between R- and S-methadone are seen
      (0.158 and 0.129 L/min, respectively). However, the lagtime after oral
      administration and the bioavailability did not show differences between the
      isomers. The data suggest that both enantiomers of methadone should be measured
      if correlations between pharmacodynamics and kinetics are made due to the
      stereoselective differences in half-life, total volume of distribution, and
      clearance.

PMID- 8738760
TI  - Should 6-thioguanine nucleotides be monitored in heart transplant recipients
      given azathioprine?
AB  - The commonly used immunosuppressive regimen after orthotopic heart
      transplantation consists of cyclosporine (CsA), azathioprine (AZA), and steroids.
      Although AZA therapy is generally regarded as unproblematic, its use can be
      associated with severe side effects, particularly myelosuppression. Since AZA is
      a prodrug, which must first be metabolized to its active metabolites, AZA
      therapy, in contrast to CsA therapy, cannot be controlled by measuring blood
      levels of this drug. Because of the myelosuppressive properties of the AZA
      metabolites, the 6-thioguanine nucleotides (6-TGN), the white blood cell count is
      usually monitored in patients on AZA therapy, and AZA is discontinued if
      neutropenia appears. In a group of 20 consecutive heart recipients, 6-TGN
      concentrations ranged from < 30 to 2,211 pmol/8 x 10(8) red blood cells (RBCs);
      levels < or = 450 pmol/8 x 10(8) RBCs were not associated with AZA-induced
      myelosuppression. Three cases of neutropenia were experienced, two of them with a
      fatal outcome. One patient died in septicemia owing to total myelosuppression. In
      this case an excessively high erythrocyte 6-TGN concentration (2,211 pmol/8 x
      10(8) RBCs) was associated with a complete deficiency of thiopurine
      methyltransferase (TPMT), one of the main AZA detoxifying enzymes. The second
      patient, who had high RBC TPMT activity, developed neutropenia during
      rehabilitation, and AZA was withdrawn. Coincidentally, in this case the CsA blood
      level was only 132 g/L, and the RBC 6-TGN level was very low (maximum 46 pmol/8 x
      10(8) RBCs). This patient rapidly developed cardiogenic shock with clinical signs
      of acute rejection and was given a second transplant on an emergency basis, but
      finally died from rejection of the second graft. Retrospectively, it was
      determined that neutropenia in this patient was not related to AZA toxicity. A
      high 6-TGN level (698 pmol/8 x 10(8) RBCs) was also seen in a third patient with
      mild neutropenia, who required allopurinol, an inhibitor of xanthine oxidase, the
      other major detoxifying enzyme for AZA. In this patient AZA therapy could be
      individually adapted by RBC 6-TGN monitoring. Based on our experience, we suggest
      that RBC 6-TGN monitoring allows for better individualization of treatment with
      AZA and may help avoid fatal complications.

PMID- 8738761
TI  - Monitoring of 8-methoxypsoralen during extracorporeal photochemotherapy: evidence
      for a "first-dose" effect.
AB  - Therapeutic monitoring of 8-methoxypsoralen (8-MOP) was studied in 12 patients
      (age range 43-85 years, weight range 48-76 kg) treated for Sezary's syndrome by
      extracorporeal photochemotherapy (ECP) for 14-41 months. Before the beginning of
      each ECP cycle (2 sessions on consecutive days at about 4-week intervals), a
      blood sample was drawn to determine the 8-MOP plasma concentration 2 h after drug
      ingestion. Plasma 8-MOP levels were measured using a high-performance liquid
      chromatography method with spectrophotometric detection. Monitoring parameters
      (dose, 2-h plasma 8-MOP concentration) showed important interindividual and
      intraindividual variations. The 8-MOP dose ranged from 0.57 to 1.04 mg/kg.
      Intraindividual variations of 2-h 8-MOP levels ranged from 21% to 75%. Of the 652
      measurements, 13% were < 100 ng/ml, the therapeutic threshold for effective ECP;
      in three of the seven patients, increasing the dose obtained levels exceeding the
      therapeutic threshold, i.e, the absorption was not saturable. Orthogonal
      regression analysis between plasma 8-MOP concentrations measured in two
      consecutive ECP sessions showed a first-dose effect: the 2-h plasma 8-MOP
      concentration was significantly lower after the first administration than after
      the second (approximately 1.26-fold). Because 8-MOP has been proven to be a
      potent suicide inhibitor of drug metabolism in rats and humans, it is possible
      that 8-MOP had an inhibitory effect on its own metabolism within the therapeutic
      dose range for ECP, which would explain in part the inter- and intraindividual
      variability in 8-MOP kinetics and first-dose effect.

PMID- 8738762
TI  - Systemic concentrations of salbutamol and HFA-134a after inhalation of salbutamol
      sulfate in a chlorofluorocarbon-free system.
AB  - The objective of this study was to determine if salbutamol was absorbed from a
      new salbutamol sulfate chlorofluorocarbon (CFC)-free metered-dose inhaler (MDI).
      Measurement of HFA-134a, the CFC-free propellant, was included to provide proof
      of delivery of this MDI. Eight healthy men received two inhalations (90
      micrograms salbutamol base equivalents per inhalation ex adapter) from the CFC
      free inhaler (MDI A) in period 1 and from a reference CFC inhaler (MDI V) in
      period 2. Eight postdose samples were collected for the determination of
      salbutamol serum levels over a 4-h period. Salbutamol levels were not
      quantifiable in most samples. Four subjects given MDI A and two given MDI V had a
      few transient salbutamol levels, which occurred in the first hour after dosing,
      within a narrow range of 1-2 ng/ml and close to the lower limit of detection (1
      ng/ml). No pharmacokinetic analyses were possible. Blood samples were also
      collected after MDI A for propellant quantitation. HFA-134a levels were seen in
      all subjects, verifying absorption. We conclude that the transient salbutamol
      serum levels can be attributed to the two-inhalation dose and not to either
      propellant system.

PMID- 8738763
TI  - Population pharmacokinetics of caffeine in neonates and young infants.
AB  - The population pharmacokinetics of caffeine were investigated in 60 neonates and
      young infants using data collected during routine therapeutic drug monitoring.
      Clearance was influenced by body weight and postnatal age, and increased in the
      presence of dexamethasone. No clinical factors were identified that influenced
      volume of distribution. The population pharmacokinetic parameter estimates were
      then tested prospectively in a further 20 neonates. Although they produced
      unbiased results, the dexamethasone effect could not be identified. A final
      analysis using all 80 patients found clearance (L/day) = 0.14 x weight (kg) +
      0.0024 x postnatal age (days) (+/- 20%) and volume of distribution = 0.82 L (+/-
      24%). Simulations based on these results indicated that the current dosage
      guidelines of 20 mg/kg loading dose of caffeine citrate followed by a 5 mg/kg/day
      maintenance dose should achieve concentrations within the traditional target
      range in > 70% of neonates.

PMID- 8738764
TI  - Determination of urinary metabolites of caffeine for the assessment of cytochrome
      P4501A2, xanthine oxidase, and N-acetyltransferase activity in humans.
AB  - Caffeine metabolism via the 3-demethylation pathway is sequentially catalyzed by
      cytochrome P4501A2 (CYP1A2), xanthine oxidase, and N-acetyltransferase. The
      activities of the three enzymes can be estimated from urinary metabolic ratios of
      four caffeine metabolites, 5-acetylamino-6-formylamino-3-methyluracil (AFMU), 1
      methyluric acid (1MU), 1-methylxanthine (1MX), and 1,7-dimethyluric acid (17DMU),
      after the ingestion of caffeine. A method for quantitation of the four
      metabolites in human urine has been developed. The method is based on a one-step
      extraction with ethyl acetate/2-propanol followed by high-performance liquid
      chromatography with UV detection. The detection limit was 1 microM for AFMU, 1MU,
      and 1MX and 2 microM for 17DMU. The intraday and interday coefficients of
      variation were < 3% and < 7%, respectively, and the accuracy was within +/- 3%.
      The method was employed in a population study of 277 healthy volunteers, each of
      whom ingested 200 mg caffeine and provided a urine sample approximately 6 h
      later. The metabolite concentration ranges in the urines were 2.1-327 microM, 4.0
      744 microM, 4.9-598 microM, and 6.4-260 microM for AFMU, 1MU, 1MX, and 17DMU,
      respectively. The CYP1A2 ratio (AFMU + 1MU + 1MX/17DMU) was significantly lower
      in women than in men, excluding smokers and oral contraceptive users. The CYP1A2
      ratio was higher in smokers than in nonsmokers, confirming the induction of
      CYP1A2 by smoking. In women using oral contraceptives, the CYP1A2 ratio was, as
      expected, significantly lower than in women not using oral contraceptives. For
      the N-acetyltransferase ratio (AFMU/1MX) and the xanthine oxidase ratio
      (1MU/1MX), no differences were seen in terms of sex, smoking habits, or the use
      of oral contraceptives. All results are in agreement with previous reports on
      CYP1A2, N-acetyltransferase, and xanthine oxidase activities in humans. Thus, the
      method is both analytically and biologically reliable for the assessment of
      CYP1A2, N-acetyltransferase, and xanthine oxidase in humans.

PMID- 8738765
TI  - Once-daily aminoglycoside dosing: impact on requests and costs for therapeutic
      drug monitoring.
AB  - Recently, much interest has focused on the use of once-daily aminoglycosides
      (ODA) in the medical literature. In late 1992, we implemented a hospital-wide ODA
      program for adult patients at our 850-bed community-teaching hospital. In the
      first phase of implementation, therapeutic drug monitoring (TDM) was accomplished
      with the use of a random serum concentration and a nomogram that had been
      developed at our institution. In the second phase, serum drug concentrations were
      eliminated on patients with normal renal function. The fully implemented program
      resulted in a 40% decrease in the request for gentamicin and tobramycin serum
      concentrations as compared with historic ordering patterns for conventional
      aminoglycoside dosing regimens. In addition, the incidence of nephrotoxicity was
      also reduced from 3 to 5% with conventional aminoglycoside dosing, to 1.2 and
      1.3% for phases 1 and 2, respectively. Furthermore, the elimination of TDM
      requests totaling 300 for gentamicin and 50 for tobramycin per month is expected
      to result in an annual institutional savings of > $100,000.

PMID- 8738766
TI  - Quality assurance procedure for monitoring tacrolimus (FK506) concentrations in
      whole blood by IMx assay.
AB  - A Quality Assurance Program for the IMx assay for FK506 in whole blood samples
      was established to monitor the performance of the assay in clinical sites
      enrolled by Fujisawa USA, Inc. Forty investigative sites participating in the
      program were required to perform assay to establish intraassay variability,
      interassay variability, and performance on blinded samples. Only two of the sites
      were required to repeat part of the program. The intraassay and interassay
      results at the sites were in good agreement with the target values obtained at
      Fujisawa Research Laboratory. Most of the coefficients of variation (CV) were
      within +/- 15%, well within the acceptance range of +/- 30%. Only a few values
      were outside the acceptance window. For the blinded samples, the CVs were
      variable and depended on the concentration of FK506 in the sample. At lower blood
      FK506 concentrations (5-10 ng/ml), the mean CVs were often outside the acceptance
      window, and many individual values were not acceptable. At concentrations of 15
      50 ng/ml, the CVs were generally acceptable. Thus individual sites can quickly
      learn to perform the FK506 IMx assay and achieve good within- and between-day
      results. The assay of lower blood concentrations of FK506 may show higher
      variability. Patients are usually monitored for clinical signs of rejection and
      toxicity in addition to blood FK506 concentrations.

PMID- 8738767
TI  - Progress report of an external quality assessment scheme for cyclosporine assay.
AB  - Beginning in 1987, an external quality assessment (EQA) scheme for cyclosporine
      (CsA) assay was organized by our Institute and supported by National Research
      Council (CNR); in 1991, the CNR EQA joined the French CsA interlaboratory program
      organized by Service de Radiopharmacie et Radioanalyse, University of Lyon.
      During the last 2 years (1993 and 1994 cycles), > 170 laboratories (from seven
      European countries) participated in this survey, assaying 44 control samples
      prepared from pooled blood of heart- and renal-transplant patients; normal pools
      added with known amounts of CsA were also distributed. During the whole EQA
      period, a trend toward the use of specific and nonisotopic techniques has been
      observed. In 1994, 91% of the collected results have been produced by specific
      methods [high-pressure liquid chromatography (HPLC) or specific immunoassays
      developed to assay the native molecule of CsA without its metabolites];in the
      same cycle, the fully automated techniques [TDx, fluorescence polarization
      immunoassay (FPIA), and enzyme-multiplied immunoassay (EMIT)] accounted for 73%
      of total results. CsA concentration measured by monoclonal specific immunoassays
      [(TDx FPIA, radioimmunoassay (RIA) Cyclo-Trac, and EMIT] was well correlated with
      those from HPLC (r = 0.99-1.00); results from EMIT were very close to those from
      HPLC, whereas results from RIA Cyclo-Trac and TDx were slightly overestimated (10
      20%). Nonspecific methods (TDx polyclonal and nonspecific RIA Cyclo-Trac)
      measured CsA concentrations 3-4 times higher than those found by HPLC. The cross
      reactivity of CsA metabolites in specific immunoassays was estimated from data of
      patients' samples and spiked samples; an interference of 6% in RIA Cyclo-Trac, 7%
      in EMIT, and 26% in TDx FPIA was found. The precision coefficient of variation
      (CV% between laboratory and between assay) of the methods observed in the 1994
      EQA cycle was 9.5 for TDx polyclonal FPIA, 10.4 for TDx monoclonal FPIA, 10.5 for
      EMIT, 10.6 for RIA specific Cyclo-Trac, 14.2 for RIA nonspecific Cyclo-Trac, and
      15.2 for HPLC.

PMID- 8738768
TI  - Cocaine and cocaethylene binding to human tissues: a preliminary study.
AB  - The tissue binding of cocaine (COC) and cocaethylene (CE) was investigated by
      equilibrium dialysis of homogenates of whole human tissue supplemented with
      either COC or CE at concentrations of 10 and 50 microM for each drug.
      Concentrations of COC and CE were measured by high-pressure liquid
      chromatography. Kidney bound COC predominantly whereas serum bound it the least
      (about one tenth as much). In contrast, for CE, most binding was noted to brain
      with the least to serum (about one twentieth as much). Heart, placenta, and liver
      showed intermediate binding overall. The binding of COC and CE to these tissues
      may be important in understanding specific target-organ activity of both
      compounds.

PMID- 8738769
TI  - Displacement of valproic acid and carbamazepine from protein binding in normal
      and uremic sera by tolmetin, ibuprofen, and naproxen: presence of inhibitor in
      uremic serum that blocks valproic acid-naproxen interactions.
AB  - Displacement of valproic acid (90-95% bound to albumin) and carbamazepine (80%
      bound to albumin) by salicylate, leading to higher concentrations of
      pharmacologically active free drugs, has been reported. We studied the
      possibility of displacement of valproic acid and carbamazepine by other strongly
      albumin-bound nonsteroidal antiinflammatory drugs tolmetin, ibuprofen, and
      naproxen. We observed statistically significant displacement of carbamazepine
      from protein binding in uremic serum at higher therapeutic concentrations of all
      three antiinflammatory drugs we studied, whereas in normal serum, we observed
      statistically significant displacement only with 75 micrograms/ml of naproxen.
      For valproic acid, we observed significant displacement even at lower therapeutic
      concentrations with all three drugs when the study was conducted using a normal
      serum pool. In the uremic serum pool, we observed significant displacements only
      with tolmetin and ibuprofen, whereas we observed no significant displacement of
      valproic acid even with higher concentrations of naproxen. We conclude that
      tolmetin, naproxen, and ibuprofen can displace both carbamazepine and valproic
      acid from protein binding, but uremic serum contains an inhibitor that blocks
      valproic acid-naproxen interaction.

PMID- 8738770
TI  - Saliva as a valid alternative to serum in monitoring intravenous caffeine
      treatment for apnea of prematurity.
AB  - Caffeine is a potentially useful alternative to theophylline for the treatment
      and prevention of apnea of prematurity because of its lower toxicity and longer
      terminal half-life. Monitoring of salivary caffeine concentrations is less
      invasive than blood sampling, especially in very sick premature neonates.
      Caffeine citrate-3 mg/kg, 15 mg/kg, or 30 mg/kg-was administered once daily for 7
      days in a randomized, parallel design to 59 newborn, premature infants with an
      initial loading dose of twice the maintenance dose. Serum and saliva samples (131
      pairs) were collected and assayed by high-performance liquid chromatography
      (HPLC) for caffeine content. Measurable caffeine concentrations in serum ranged
      from 0.28 to 93.3 mg/L and in saliva from 0.35 to 91.5 mg/L. The mean ratio of
      the saliva-to-serum concentrations was 0.924. There was no significant difference
      in precision between the serum and salivary data. The mean serum caffeine
      concentration was 29.9 mg/L, and the mean salivary concentration was 27.7 mg/L,
      indicating a small negative bias for saliva versus serum monitoring. Salivary
      caffeine concentration monitoring is a satisfactory alternative to blood sampling
      across a wide range of caffeine doses used to treat apnea.

PMID- 8738771
TI  - A method for rapid determination of zotepine by gas chromatography-mass
      spectrometry.
AB  - A rapid and sensitive method using solid-phase extraction and gas chromatography
      mass spectrometry (GC-MS) has been developed for the determination of zotepine
      (ZTP), an atypical neuroleptic, in human plasma. The detection limit of ZTP was 1
      microgram/L. Standard curves over the concentration range from 2.5 to 100
      micrograms/L had a good linearity. Intraassay variability ranged from 2.2 to 3.3%
      and interassay variability from 3.5 to 6.6% at the concentration range of 5-75
      micrograms/L. Our preliminary data of single-dose kinetics of ZTP by using this
      method suggested that the peak time and elimination half-life was much longer
      than previously reported, and that there appeared to be a second peak after 10-12
      h of ZTP administration, indicating the possibility of the presence of
      enterohepatic recirculation.

PMID- 8738772
TI  - Automated determination of dextromethorphan and its main metabolites in human
      plasma by high-performance liquid chromatography and column switching.
AB  - An automated column-switching technique coupled to isocratic high-performance
      liquid chromatography (HPLC) with fluorescence detection was developed for
      simultaneous determination of dextromethorphan and its three major metabolites,
      dextrorphan, hydroxymorphinan, and methoxymorphinan. After cleavage of conjugates
      by incubation with glucuronidasearylsulfatase at 37 degrees C for 15 h, plasma
      samples were injected directly into the HPLC system. Dextromethorphan and
      metabolites were retained on a cleanup column (10 x 4.6 mm internal diameter
      [ID]) filled with cyanopropyl (CN) material (Hypersil CPS, 10-microns article
      size) while interfering proteins and lipids were washed to waste. After column
      switching, the drugs were eluted from the cleanup column and separated on
      Spherisorb CN material (5-microns particle size, column size 250 x 4.6 mm ID).
      Fluorescence detection was carried out with an excitation wavelength of 220 nm
      and an emission wavelength of 305 nm. Sample cleanup and HPLC separation were
      completed within 20 min. Regression analyses found linearity (r > 0.99) between
      drug concentration and detector response over a wide range-5-220 ng/ml for
      dextromethorphan, 5-550 ng/ml for dextrorphan, 5-500 ng/ml for hydroxymorphinan,
      and 5-200 ng/ml for methoxymorphinan. The limit of quantification was
      approximately 5 ng/ml, and the recovery was > 90% for all compounds. At
      concentrations of 20-500 ng/ml, the intra- and interassay coefficients of
      variation ranged from 3.5 to 14.6% and from 7.0 to 14.0%, respectively. The
      method is suitable for in vivo phenotyping of CYP2D6 activity, which catalyzes
      the O-demethylation of dextromethorphan to dextrorphan, and is also applicable to
      pharmacokinetic studies in man.

PMID- 8738773
TI  - Influence of heparin on the assay of amitriptyline, clomipramine, and their
      metabolites.
AB  - In this study the effect of the use of lithium heparin containers on the plasma
      levels of amitriptyline, clomipramine, and their metabolites was investigated.
      Twenty-five patients (10 men and 15 women, mean age 51.8 +/- 14.9 years) taking
      either amitriptyline or clomipramine in a daily dosage varying from 50 to 250 mg
      entered the study after giving informed consent. From each patient, blood samples
      were taken in a sodium edetate container and in a lithium heparin container in
      random order. Parent compound levels are equal in sodium edetate and lithium
      heparin containers. Metabolite levels are 5.6% lower in lithium heparin
      containers. This difference is not considered clinically relevant.

PMID- 8738774
TI  - Stability of therapeutic drug measurement in specimens collected in VACUTAINER
      plastic blood-collection tubes.
AB  - Recently Becton-Dickinson marketed a plastic serum-separator tube that uses the
      same serum-separator gel as the glass tubes. We studied the stability of
      therapeutic drugs stored in plastic tubes by comparing it with the stability of
      drugs stored in glass serum-separator tubes and plain red-top glass tubes. We
      observed no absorption of caffeine, primidone, N-acetylprocainamide,
      procainamide, theophylline, tobramycin, ethosuximide, acetaminophen, amikacin,
      valproic acid, methotrexate, salicylate, and cyclosporine in either plastic or
      glass serum-separator tubes. On the other hand, concentrations of lidocaine,
      quinidine, phenobarbital, and phenytoin were reduced after storing in both
      plastic and glass serum-separator tubes, especially with prolonged storage and
      small sample volume. The reduction in concentrations were due to slow absorption
      of those drugs by serum-separator gel.

PMID- 8738775
TI  - Effect of the transition from intravenous to oral dosing on cyclosporin-A trough
      concentrations in liver transplant patients.
AB  - Cyclosporin A (CsA) absorption is low and variable after liver transplantation,
      and during the intravenous-oral transition period CsA concentrations may not be
      maintained within the therapeutic range. Trough whole blood CsA concentrations
      were measured by high-performance liquid chromatography before and after the
      transition period in 27 liver transplant patients. Mean (SD) CsA concentrations
      decreased from 291 (92) to 198 (96) ng/ml (p < 0.001). When analyzed on
      individual charts, a decrease was observed in 15 of 27 patients and it was
      associated with a duration of 2 days or less (p < 0.01) and a total bilirubin
      value below 3.5 mg/dl (p < 0.05). Our results show that, despite therapeutic drug
      monitoring, CsA blood concentrations may decrease during the intravenous-oral
      transition period.

PMID- 8738776
TI  - Critical issues in therapeutic drug monitoring: pathways to the future.

PMID- 8738777
TI  - Biomechanical model for the myogenic response in the microcirculation: Part I-
      Formulation and initial testing.
AB  - The pressure dependent or myogenic contraction of arterioles is one of the most
      fundamental control mechanisms of microvascular perfusion. While many
      experimental observations have been obtained on the myogenic response, no
      generally accepted biomechanical model has been formulated. A novel biomechanical
      theory is proposed based on two fundamental assumptions: the arteriolar wall
      exhibits viscoelastic properties before and during myogenic contractions, and the
      contraction is achieved by a pressure dependent change of reference length. The
      formulation of the model and its application to different experimental procedures
      on microvascular smooth muscle in the literature is presented. The model
      describes closely a broad spectrum of steady and unsteady pressure dependent
      diameter variations of arterioles under a pressure dependent stimulus.

PMID- 8738778
TI  - Biomechanical model for the myogenic response in the microcirculation: Part II-
      Experimental evaluation in rat cremaster muscle.
AB  - In order to test experimentally a novel model for myogenic contraction of the
      arterioles, presented in Part I of this series, a sequence of in-vivo studies was
      performed on arterioles of rat cremaster muscle using a modified "Box Method."
      The tissue was enclosed in a sealed chamber in which the extravascular pressure
      could be changed as a means of stimulating the myogenic response. The
      microvascular pressures were measured using an improved cremaster preparation
      with intact distal feeder. The experiment consists of measurements of a static
      myogenic response and the response to a step extravascular pressure, as well as
      passive viscoelastic properties of the arteriole. These measurements served to
      determine the parameters involved in the theoretical model. The model prediction
      were then compared with in-vivo observations during a ramp and during oscillatory
      extravascular pressure changes in the same arterioles. The results indicate that
      the model is capable of quantitatively predicting time dependent in-vivo changes
      in response to transmural pressure. The measured model parameters suggest an
      increase in myogenic activity from proximal arcade arterioles to more distal
      transverse arterioles in cremaster muscle of Wistar rats.

PMID- 8738779
TI  - Particle volumetric residence time calculations in arterial geometries.
AB  - The quantification of particle (platelet) residence times in arterial geometries
      is relevant to the pathogenesis of several arterial diseases. In this manuscript,
      the concept of "volumetric residence time" (VRT) is introduced. The VRT takes
      into account where particles accumulate and how long they remain there, and is
      well-suited to characterizing particle distributions in the complex geometries
      typical of the cardiovascular system. A technique for the calculation of
      volumetric residence time is described, which assumes that platelets are
      neutrally buoyant passive tracer particles, and which tracks small Lagrangian
      fluid elements containing a uniform concentration of platelets. This approach is
      used to quantify particle (platelet) residence times in the region of a modeled
      stenosis with a 45 percent area reduction. Residence time distributions are
      computed for a representative population of platelets, and for a subpopulation
      assumed to be "activated" by exposure to shear stresses above a threshold value.
      For activated platelets, high particle residence times were observed just distal
      to the apex of the stenosis throat, which can be explained by the presence of
      high shear stresses and low velocities in the throat immediately adjacent to the
      vessel wall. Interestingly, the separation zone distal to the stenosis showed
      only modestly elevated residence times, due to its highly mobile and transient
      nature. This calculation demonstrates the utility of the VRT concept for
      cardiovascular studies, particularly if a subpopulation of all particles is to be
      tracked. We conclude that the volumetric residence time is a useful tool.

PMID- 8738780
TI  - Flow measurements in an aortocoronary bypass graft casting.
AB  - Flow visualization and pressure measurements were carried out in a singel valve
      saphenous vein casting which was made from a saphenous vein segment obtained from
      a bypass patient at Cedars Sinai Medical Center. Dye was injected to understand
      the flow around the valve. The dye showed very complex flow patterns around the
      valve and in the valve sinus, and the cavity formed by a ligated branch. For
      steady flow, pressure drops across the valve were 0.72, 2.0 and 6.3 mmHg for the
      physiological flow rates of 45, 84, and 169 ml/min, respectively. Overall
      pressure drop across the casting (compared to Poiseuille flow for a straight
      tube) increased with the flow rate, being 130 to 290 percent higher over this
      flow rate range. In the case of pulsatile flow, pressure drops across the valve
      were 0.95 and 3.0 mmHg for the flow rates of 47 and 87 ml/min which were 26 and
      43 percent higher than those of steady flow. Overall pressure drop was 220 and
      360 percent higher for those flow rates compared to Poiseuille flow. The measured
      spatial pressure distributions along the casting and flow visualization indicated
      the global nature of the flow field with the accelerated flow through the valve
      separating and reattaching downstream along the wall in the pressure recovery
      region. Atherosclerosis may be prone to occur in the lower shear region along the
      wall beyond the valve tip in the reattachment region, as we have observed in vivo
      in rabbit experiments.

PMID- 8738781
TI  - Numerical analysis of steady flow in aorto-coronary bypass 3-D model.
AB  - Intimal hyperplasia and atherosclerosis have a predominant role in the failure of
      coronary artery bypass procedures. Theoretical studies and in vivo observations
      have shown that these pathologies are much more likely to occur in the proximity
      of end-to-side anastomosis, thus indicating that fluid dynamic conditions may be
      included in the pathogenic causes of the initiation, progression and complication
      of intimal hyperplasia. In order to study the fluid dynamics at the anastomosis
      of an aortocoronary bypass, a three-dimensional mathematical model based on a FEM
      approach was developed. Steady-state simulations were studied in two different
      geometrical models of anastomosis which differ in their insertion angles (45 and
      60 degree). Flow fields with three-dimensional helical patterns, secondary flows,
      and shear stresses were also investigated. The results show the presence of low
      shear stresses on the top wall just beyond the toe of the anastomosis and in the
      region of the coronary artery before the junction. A high wall shear stress
      region is present on the lateral wall of the coronary artery immediately
      downstream from the anastomosis. The influence of flow rate distribution on the
      secondary flows is also illustrated. These results confirm the sensitivity of
      flow behavior to the model's geometrical parameters and enhance the importance of
      reproducing the anastomosis junction as closely as possible in order to evaluate
      the effective shear stress distribution.

PMID- 8738782
TI  - Large curvature effect on pulsatile entrance flow in a curved tube: model
      experiment simulating blood flow in an aortic arch.
AB  - We measured the velocity profiles of pulsatile entrance flow in a strongly curved
      tube using a laser-Doppler anemometer in order to simulate blood flow in the
      aortic arch under various conditions, i.e., a ratio of tube to curvature radius
      of 1/3, Womersley parameters of 12 and 18, and peak Dean number up to 1200. Axial
      isovelocity contours of the cross-section showed the potential vortex to be near
      the entrance, and with the maximum velocity there being skewed towards the inner
      wall; thereafter shifting towards the outer wall. During the deceleration phase,
      reverse axial flow occurred near the inner wall, and a region of this flow
      extended downstream. The large curvature contributes to the enhancement of the
      secondary flow and flow reversal, which elevates the wall-shear stress
      oscillations. The location of elevated wall-shear oscillations corresponds to the
      vessel wall region where atherosclerotic formation frequently occurs; thereby
      indicating that both the large curvature and pulsatility play key roles in
      formation of localized atherosclerotic lesions.

PMID- 8738783
TI  - Application of a mechanical filter to an artificial heart.
AB  - A mechanical filter developed to improved the performances of an artificial heart
      whose electrical motor has a reciprocating motion is presented. The filter phases
      the mechanical load strongly reducing its inertial component (which is of the
      same order of magnitude as the useful load). The analysis reported for a
      prototype developed by us shows that when its rate is equal to the first resonant
      frequency of the filter, a reduction of about 50 percent for the maximum value of
      the torque due to inertial and friction forces is obtained.

PMID- 8738785
TI  - Numerical simulation of oil-droplet cleavage by surfactant.
AB  - We present numerical computations of the deformation of an oil-droplet under the
      influence of a surface tension gradient generated by the surfactant released at
      the poles (the Greenspan experiment). We find this deformation to be very small
      under the pure surface tension gradient. To explain the large deformation of oil
      droplets observed in Greenspan's experiments, we propose the existence of a
      phoretic force generated by the concentration gradient of the surfactant. We show
      that this hypothesis successfully explains the available experimental data and we
      propose some further tests.

PMID- 8738784
TI  - The measurement of temperature with electron paramagnetic resonance spectroscopy.
AB  - An electron paramagnetic resonance (EPR) technique, potentially suitable for in
      vivo temperature measurements, has been developed based on the temperature
      response of nitroxide stable free radicals. The response has been substantially
      enhanced by encapsulating the nitroxide in a medium of a fatty acid mixture
      inside a proteinaceous microsphere. The mixture underwent a phase transition in
      the temperature range required by the application. The phase change dramatically
      altered the shape of the EPR spectrum, providing a highly temperature sensitive
      signal. Using the nitroxide dissolved in a cholesterol and a long-chain fatty
      acid ester, we developed a mixture which provides a peakheight ratio change from
      3.32 to 2.11, with a standard deviation of 0.04, for a temperature change typical
      in biological and medical applications, from 38 to 48 degrees C. This translated
      to an average temperature resolution of 0.2 degree C for our experimental system.
      The average diameter of the nitroxide mixture-filled microspheres was
      approximately 2 microns. Therefore, they are compatible with in vivo studies
      where the microspheres could be injected into the microvasculature having a
      minimum vessel diameter of the order of 8 microns. This temperature measuring
      method has various potential clinical applications, especially in monitoring and
      optimizing the treatment of cancer with hyperthermia. However, several problems
      regarding temperature and spatial resolution need to be resolved before this
      technique can be successfully used to monitor temperatures in vivo.

PMID- 8738786
TI  - A mathematical model for the morphology of the pulmonary acinus.
AB  - A computational method is proposed for the construction of a three-dimensional
      space-filling model of an acinar ventilatory unit. Its geometry consists of
      truncated octahedra arranged in a cuboidal block. The ducts and alveoli are
      formed by opening specific common faces between polyhedra. The branching
      structure is automatically computed using algorithms solely to maximise the
      number of alveoli and minimise the average path lengths; it is not formed with
      reference to published experimental data. Properties of the model such as the
      total alveolar and ductal volumes, the distribution of individual path lengths to
      the alveolar sacs, and the average number of ducts per generation are calculated.
      The predicted morphology of the model compares well with published data for rat
      lungs.

PMID- 8738787
TI  - Effects of restressing on the mechanical properties of stress-shielded patellar
      tendons in rabbits.
AB  - We studied the effects of restressing on the mechanical properties and morphology
      of stress-shielded rabbit patellar tendons. After completely unloading the
      patellar tendon for 1 to 3 weeks, tension was again applied to the tendon for
      subsequent 3 to 12 weeks. Although the stress shielding markedly decreased the
      tangent modulus and tensile strength of the tendon, restressing significantly
      increased them. However, the mechanical properties of the tendon were not
      completely recovered even after a prolonged period of restressing. The
      microstructure of the tendon was also restored by restressing, although the
      recovery was incomplete. These results indicate that the mechanical properties
      and morphology of tendinous tissue change in response to mechanical demands.

PMID- 8738788
TI  - A single integral finite strain viscoelastic model of ligaments and tendons.
AB  - A general continuum model for the nonlinear viscoelastic behavior of soft
      biological tissues was formulated. This single integral finite strain (SIFS)
      model describes finite deformation of a nonlinearly viscoelastic material within
      the context of a three-dimensional model. The specific form describing uniaxial
      extension was obtained, and the idea of conversion from one material to another
      (at a microscopic level) was then introduced to model the nonlinear behavior of
      ligaments and tendons. Conversion allowed different constitutive equations to be
      used for describing a single ligament or tendon at different strain levels. The
      model was applied to data from uniaxial extension of younger and older human
      patellar tendons and canine medial collateral ligaments. Model parameters were
      determined from curve-fitting stress-strain and stress-relaxation data and used
      to predict the time-dependent stress generated by cyclic extensions.

PMID- 8738790
TI  - Microdamage and osteocyte-lacuna strain in bone: a microstructural finite element
      analysis.
AB  - Damage accumulation in living tissues occurs when the rate of damage formation is
      greater than the rate of damage repair. For very large increases in the loading
      rate of bones, this can result in "stress fractures" due to the growth and
      coalescence of fatigue related microdamage. At lower increases of loading rates,
      the damage accumulation process is halted because there is time for adaptive bone
      remodeling to occur in response to the new load. However, it is not known if
      there is a relationship between microdamage and bone remodeling per se. One
      hypothesis for the control of bone remodeling is that osteocytes sense strains
      and mediate osteoblastic and osteoclastic activity. The purpose of this study was
      to investigate whether damage generates strains which may trigger bone
      remodeling. If this were true, then accumulative damage would cause adaptive bone
      remodeling. This study applies the methods of finite element analysis to
      determine the effect of observed damage mechanisms on the proposed sensors of
      remodeling in Haversian bone. Individual lamellae are modeled and osteocyte
      lacunae are included in a generalized plane strain geometric representation. It
      is predicted that microdamage alters the local deformation behavior around
      lacunae, and that the changes increase as microdamage accumulates. Hence, if
      damage accumulates in a bone, it could be sensed as a change in strain at a
      microstructural level. The results give theoretical support to the experimental
      studies that have shown a correlation between microdamage and the initiation of
      resorption as a first step in bone remodeling.

PMID- 8738789
TI  - A sagittal plane model of the knee and cruciate ligaments with application of a
      sensitivity analysis.
AB  - In this investigation the complex multi-bundle structure of the cruciate
      ligaments and their interaction with the tibiofemoral joint was modeled
      analytically by representing the different regions of the cruciates with ligament
      elements. A sensitivity analysis was then performed to describe the effect that
      variations of the model input parameters had on the model variables (outputs).
      The effect that the cruciate ligament bundles had in controlling joint kinematics
      was dependent on knee flexion angle, and the load applied to the tibiofemoral
      joint. For passive range of knee motion with the thigh in the horizontal plane (a
      common rehabilitation activity), all cruciate ligament bundles were strained with
      the joint positioned between 0 and 10 deg of knee flexion, between 10 and 50 deg
      only the anterior bundle of the posterior cruciate ligament A-PCL was strained,
      and from 50 to 90 deg both the anteromedial portion of the anterior cruciate
      ligament A-ACL and the A-PCL were strained. This finding indicates that a strain
      distribution about a transverse cross section of the cruciates exists, and
      demonstrates the importance of differentiating between the strained and
      unstrained (unloaded) states of these ligaments. The strain value of a cruciate
      ligament bundle was an indication of how the bundle controls joint kinematics,
      while the unstrained values describe how much the ligament bundle must deform
      before it becomes strained and a restraint to tibiofemoral joint motion. In
      response to anterior and posterior directed loads, applied parallel to the tibial
      plateau, the respective, ACL and PCL load values were larger in magnitude. The
      sensitivity of the model outputs to the input parameters was highly dependent on
      knee flexion angle. The geometrical input parameters of the model (including the
      ligament insertion site locations and articular surface geometry) had the most
      pronounced effect on the model output quantities, while the stiffness and initial
      strain conditions of the ligament bundles had less of an effect on the model
      outputs. When loaded, the strain values of the ligament bundles were sensitive to
      the ligament insertion site position. The greatest sensitivity of the model
      outputs was the femoral insertion of the ACL; supporting clinical impressions and
      previous experimental findings. Changes in the anterior-posterior dimension of
      the femoral articular surface did not produce a substantial effect on the model
      outputs, while changes in the proximal-distal dimension created a large effect;
      similar results were found for the tibial surface dimensions. These findings
      indicate that rigid body contact between the articular surfaces may not be a
      realistic assumption particularly with application to the prediction of
      tibiofemoral compressive loading and the force/strain values of the cruciate
      ligament elements. This also has important implications for the design and
      clinical application of total knee replacements (that function as rigid bodies),
      particularly those that spare the PCL.

PMID- 8738791
TI  - A mathematical expression of three-dimensional configuration of the scoliotic
      spine.
AB  - Three-dimensional configuration of the scoliotic spine was mathematically
      expressed by a spatial curve passing through each vertebral centroid ("vertebral
      body line"). Three-dimensional location of the vertebral centroid was determined
      from digitization on the frontal and sagittal roentgenograms. Cobb angle, which
      is clinically used for measuring scoliosis curvature, was calculated in space to
      evaluate scoliosis deformity three-dimensionally. In forty-five scoliotic spines,
      regardless of curvature and curve patterns, the spinal configurations were
      excellently approximated by vertebral body lines. Vertebral body lines swerved
      from the sagittal plane at the end vertebrae, but aligned on a certain plane
      within the scoliosis region. Three-dimensional Cobb angle, which was larger than
      that in the frontal plane, can be utilized to evaluate the scoliosis deformity.

PMID- 8738792
TI  - A rehabilitation treadmill with software for providing real-time gait analysis
      and visual feedback.

PMID- 8738793
TI  - Computational models of the effects of hydration on corneal biomechanics and the
      results of radial keratotomy.

PMID- 8738794
TI  - Normal six-degree-of-freedom motions of knee joint during level walking.
AB  - The purpose of this study was to find an effective way for in vivo measurement of
      joint motion and give the normal knee motion according to this method. The joint
      model proposed by Grood and Suntay (1983) was chosen; the origin of the tibia was
      modified for the convenience of in vivo test. A computerized 6 degree-of-freedom
      electrogoniometer (EGM) was used in the measurement. Repeated tests on one
      subject were performed to establish the reliability of the method. Knee motions
      obtained from 42 males during level walking were expressed as flexion-extension,
      abduction-adduction, external-internal rotation, lateral-medial translation,
      anterior-posterior translation, and superior-inferior translation. The results
      showed that, with the proper choice of the origin of the tibia, the EGM could
      depend much less on external landmarks and be more effective for the joint
      measurement.

PMID- 8738795
TI  - Passive material properties of intact ventricular myocardium determined from a
      cylindrical model.

PMID- 8738796
TI  - Chronic dialysis in patients over age 65.
AB  - In the United States, persons over the age of 65 are expected soon to become the
      majority of those people who will require maintenance dialysis therapy. Many of
      these individuals have numerous comorbid medical complications, which, together
      with altered physiologic adaptation related to aging, create a great challenge
      for the nephrologist. Despite a considerably lower group survival rate and
      increased hospitalization utilization as compared with younger patients, many
      elderly dialysis patients tolerate therapy very well and appear quite satisfied
      with the quality of their lives. Both hemodialysis and peritoneal dialysis are
      suitable treatment modalities for elderly patients, but recommendations regarding
      type of dialysis must be individualized, taking both medical and psychosocial
      issues into consideration. Vascular access problems are particularly important
      for the elderly and contribute to significant morbidity. Malnutrition and
      cardiovascular complications also require special attention. Withdrawal from
      dialysis appears to be increasingly common among elderly ESRD patients and
      highlights the need for the completion of advance directives. A trial of dialysis
      may allow elderly patients and their families additional time to decide whether
      long-term dialysis is deemed appropriate.

PMID- 8738797
TI  - Acute renal failure and the MELAS syndrome, a mitochondrial encephalomyopathy.
AB  - Melas (mitochondrial encephalomyopathy with lactic acidosis and stroke-like
      episodes) is one of a group of heterogeneous yet clinically distinct syndromes
      ascribed to a defect in mitochondrial function. Here, the case of a patient
      diagnosed with the MELAS syndrome who subsequently developed acute renal failure
      is reported. Although no clear renal insult was evident at the time, the clinical
      picture was consistent with the diagnosis of acute tubular necrosis. The
      patient's renal function subsequently returned to baseline. This article reviews
      the literature concerning renal involvement in the mitochondrial
      encephalomyopathies, including MELAS, and proposes a mechanism by which patients
      suffering from mitochondrial disorders may be more susceptible to renal hypoxic
      injury and acute renal failure.

PMID- 8738798
TI  - Angiotensin II modulates glomerular capillary permselectivity in rat isolated
      perfused kidney.
AB  - Studies in experimental animals and humans have documented that inhibition of the
      renin-angiotensin system by angiotensin-converting enzyme inhibitors reduces
      urinary protein excretion rate and retards the development of renal injury. Here
      we sought to investigate whether angiotensin II (All) modified the size-selective
      properties to macromolecules of the glomerular capillary barrier in isolated
      perfused rat kidney preparation. Compared with basal values, continuous All
      infusion into the renal artery at the rate of 3 or 8 ng/min, but not at 0.6
      ng/min, induced a progressive and significant increase in urinary protein
      excretion rate. Evaluation of the sieving properties of the glomerular barrier by
      fractional clearance of polydisperse Ficoll showed that All significantly
      enhanced the filtration of tracer molecules of radil > or = 34A. All-induced
      changes in urinary protein excretion rate and in Ficoll fractional clearance were
      completely prevented by pretreatment with the specific All Type 1 receptor
      antagonist SR 47436.

PMID- 8738799
TI  - Expression of vascular permeability factor (VPF/VEGF) is altered in many
      glomerular diseases.
AB  - Vascular permeability factor (VPF), also known as vascular endothelial growth
      factor (VEGF), is a potent enhancer of microvascular permeability and a selective
      endothelial cell growth factor. In normal human kidney, VPF/VEGF mRNA and protein
      are strongly expressed by visceral glomerular epithelial cells, and VPF/VEGF may
      be an important regulator of glomerular endothelial cell function. This study
      examined 47 renal biopsies from patients with a variety of glomerular diseases
      for expression of VPF/VEGF mRNA and protein by in situ hybridization and
      immunohisto-chemistry. In many glomerular diseases, VPF/VEGF-expressing cells
      were decreased in number or absent in areas of focal or global glomerular
      sclerosis. Decreased numbers of VPF/VEGF-expressing cells in glomeruli were also
      noted in amyloidosis, diabetes, crescentic glomerulonephritis, and diffuse
      endocapillary proliferative glomerulonephritis associated with systemic lupus
      erythematosus. Normally, release of VPF/ VEGF must be under strict control
      because it is some 50,000 times more potent than histamine as an inducer of
      microvascular permeability. Damage to visceral epithelial cells in a variety of
      glomerular diseases has the potential for releasing relatively large amounts of
      VPF/VEGF locally, leading to increased glomerular permeability. In addition,
      because VPF/ VEGF is also an endothelial growth factor, the loss of normal,
      controlled secretion of VPF/VEGF after damage to visceral epithelial cells could
      lead to important alterations in glomerular endothelial cell function.

PMID- 8738800
TI  - Arteriolar wall thickening, capillary rarefaction and interstitial fibrosis in
      the heart of rats with renal failure:the effects of ramipril, nifedipine and
      moxonidine.
AB  - In experimental renal failure, increased intramyocardial arteriolar wall
      thickness, reduced myocardial capillary density, and increased cardiac
      interstitium are found. The extent to which such alterations can be modified by
      therapeutic interventions has not been investigated to date. The purpose of this
      study was to examine the effects of Ramipril, Nifedipine and Moxonidine on these
      structural changes. Sham-operated and subtotally nephrectomized (SNX) 300-g male
      Sprague-Dawley rats (N = 7 to 11) were left untreated (N = 9) or treated with
      Ramipril (0.5 mg/kg body wt per day; N = 7), Nifedipine (30 mg/kg body wt per
      day; N = 9), or Moxonidine (10 mg/kg body wt per day; N = 8) for 8 wk. After
      perfusion fixation, heart and aorta were examined by stereological techniques.
      Aortic wall thickness was significantly higher in SNX than in sham-operated
      control rats and was similarly lowered by all three interventions. In contrast,
      the wall thickness of intramyocardial arterioles was significantly higher in SNX;
      this was prevented by Ramipril and Nifedipine, but not by Moxonidine.
      Intramyocardial capillary length density (Lv) was significantly lower and
      interstitial volume density (Vv) significantly higher in untreated SNX. Reduction
      of capillary length density was completely prevented by Moxonidine and in part by
      Ramipril. The increase in cardiac interstitial volume density was completely
      prevented by Ramipril and was partially prevented by Moxonidine or Nifedipine
      treatment. The following conclusions can be drawn from the results: (1) all
      agents normalize aortic wall thickness, but only calcium channel blockers and
      angiotensin-converting enzyme (ACE) inhibitors prevent intramyocardial arteriolar
      wall thickening: (2) intramyocardial arteriolar wall thickening, capillary
      rarefaction, and expansion of the cardiac interstitium are seen in SNX even after
      lowering the blood pressure to subnormal levels; i.e., changes in systemic blood
      pressure cannot completely explain the altered vascular structure in renal
      failure; (3) the effects of Ramipril, Nifedipine, and Moxonidine on
      cardiovascular structures in experimental renal failure are not completely
      accounted for by their hemodynamic actions.

PMID- 8738801
TI  - Renal interstitial sclerosis in aging: effects of enalapril and nifedipine.
AB  - The effects of nifedipine and enalapril on age-associated renal interstitial
      fibrosis were investigated in 60 CF1 female mice. Mice received 20 mg enalapril
      (ENAL) per L (N = 20), or 40 mg nifedipine (NIF) per L (N = 20) in their drinking
      water. Control (CONT) mice received tap water ad libitum. The percentages of both
      interstitial peritubular sclerosis (IPS) in cortex and interstitial medullary
      sclerosis (IMS) were determined. Kidney tissue was studied using immunological
      techniques and optical (OM) and electron microscopy (EM) to analyze the
      expression of renin. alpha-SM-actin and vimentine expression were also evaluated.
      The results showed that blood pressure levels in ENAL or NIF animals were not
      different from those of CONT. Renin expression was observed in arcuate vessels
      (AV) in ENAL animals, whereas no renin staining in AV was found in either NIF or
      CONT animals. Renin immunoreactivity in the juxtaglomerular apparatus was more
      intense in ENAL mice, as compared with NIF or CONT animals. Laboratory testing
      showed the following values: proteinuria (mg/mL): CONT 6.1 +/- 0.6, NIF 11.2 +/-
      2.3, and ENAL 1.0 +/- 0.6 (P < 0.05); creatinine: CONT 1.37 +/- 0.24, NIF 0.87 +/
      0.16, and ENAL 0.63 +/- 0.1 (P < 0.01). The percentages of interstitial
      sclerosis were: %IPS: CONT 18.12 +/- 1.1, NIF 17.40 +/- 0.9, and ENAL 3.42 +/-
      1.3 (P < 0.01); %IMS: CONT 23.41 +/- 1.5, NIF 21.80 +/- 1.9, and ENAL 6.12 +/-
      1.2 (P < 0.01). Percentages of alpha-SM-actin expression were: CONT 13.10 +/-
      1.9, NIF 13.80 +/- 0.2, and ENAL 1.00 +/- 0.1 (P < 0.01). Vimentine staining
      showed no differences among the groups. It was concluded that enalapril reduces
      the peritubular and medullar interstitial fibrosis, whereas nifedipine has no
      effect.

PMID- 8738802
TI  - Individual and combined effects of verapamil or trandolapril on attenuating
      hypertensive glomerulopathic changes in the stroke-prone rat.
AB  - Previous studies have demonstrated differences in the progression to
      glomerulosclerosis with the use of calcium channel blockers (CCB). The results
      with angiotensin-converting enzyme (ACE) inhibitors are more consistent.
      Moreover, only two studies have examined the combined effects of these drug
      classes on the development of glomerulosclerosis. The aim of the study presented
      here was to test the hypothesis that nonhypotensive doses of the combination (VT)
      of a nondihydropyridine CCB, verapamil (V), and an ACE-inhibitor, trandolapril
      (T), will slow the development of glomerulosclerosis better than either agent
      alone in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were
      randomized to treatment in one of three groups with nonhypotensive doses of these
      agents; a fourth group served as control (C). The control rats developed
      significant increases in proteinuria compared with the other groups (C, 190 +/-
      35 mg.kg-1.d-1 versus VT, 19 +/- 12 mg.kg-1.d-1; P < 0.05). This finding
      correlated with the degree of glomerulosclerosis (mean severity grading for C,
      3.31 +/- 0.21 versus VT, 1.6 +/- 0.51; P < 0.05). Moreover, there was no
      significant reduction in arterial pressure between these groups (C, 282 +/- 5
      versus VT, 259 +/- 13 mm Hg; P = 0.12). Despite persisting hypertension, the rise
      in proteinuria was also attenuated in both the V group (57 +/- 21 mg.kg-1.d-1)
      and the T group (43 +/- 24 mg.kg-1.d-1). However, compared with the control rats,
      kidney morphology was unchanged. Lastly, creatinine clearance was better
      preserved in the VT group compared with the control group (C, 0.57 +/- 0.01
      versus VT, 0.74 +/- 0.06 mL.min-1.100 g-1; P < 0.05). It was concluded that the
      combination of nonhypotensive doses of VT attenuates the rise in proteinuria and
      progression to glomerulosclerosis. This study supports the concept that VT may
      have effects on the glomerulus that are independent of blood pressure reduction.

PMID- 8738803
TI  - Angiotensin II and calcium blockers prevent glomerular phenotypic changes in
      remnant kidney model.
AB  - Recent studies on various models of glomerular diseases indicate that glomerular
      injury is associated with the phenotypic modulation of glomerular cells. However,
      the effect of renoprotective agents on glomerular phenotype remains to be
      determined. This study examined the effects of angiotensin II Type 1 (AT1)
      receptor antagonists and calcium antagonists on glomerular phenotypic changes in
      rats with subtotal renal ablation. Rats were subjected to 5/6 nephrectomy and
      were given oral TCV-116, a selective AT1 receptor antagonist (1 mg/kg),
      manidipine, a dihydropyridine calcium antagonist (3 mg/kg), or vehicle for 8 wk.
      Glomerular phenotypic modulation was determined by the staining of alpha-smooth
      muscle actin and desmin in glomerular cells with an immunohistochemical
      technique. At the start of drug treatment, alpha-smooth muscle actin and desmin
      were already significantly expressed in the glomerular cells of 5/6
      nephrectomized rats, in contrast to a negligible glomerular expression of these
      proteins in sham-operated rats. Treatment of 5/6-nephrectomized rats with TCV-116
      or manidipine significantly decreased glomerular expression of alpha-smooth
      muscle actin and desmin, thereby indicating that these drugs prevented glomerular
      phenotypic changes in 5/6-nephrectomized rats. Furthermore, their inhibitory
      effects on glomerular phenotypic modulation were associated with the prevention
      of glomerular cell proliferation, hypertrophy, and sclerosis. Therefore, this
      study provides the first evidence that the renoprotection is linked to the
      prevention of glomerular phenotypic modulation and supports the idea that this
      phenotypic modulation may serve as an important cellular marker of glomerular
      injury.

PMID- 8738804
TI  - Proteinase 3, the major autoantigen of Wegener's granulomatosis, enhances IL-8
      production by endothelial cells in vitro.
AB  - Proteinase 3 is the major target antigen of antineutrophil cytoplasmic
      autoantibodies (ANCA) in Wegener's granulomatosis and is contained in the
      azurophilic granules of polymorphonuclear neutrophils, the dominant cell type in
      vascular lesions during the early stages of systemic vasculitis. This study
      questioned whether neutrophil lysosomal enzymes, once released at the site of
      inflammation, are able to potentiate the influx of additional neutrophils by
      enhancing the production of the chemotactic cytokine interleukin-8 (IL-8) by
      endothelial cells. Therefore, human umbilical vein endothelial cells in culture
      were incubated with varying concentrations of highly purified proteinase 3, human
      neutrophil elastase, and cathepsin G for different time periods. The supernatants
      were subsequently assessed for IL-8 antigen by using a sandwich ELISA. The
      presence of both proteinase 3 and elastase resulted in an increased production of
      IL-8, up to 15.6- and 4.2-fold, respectively, in a dose- and time-dependent
      fashion. Cathepsin G did not influence IL-8 production. Although the addition of
      an alpha 1-proteinase inhibitor completely abrogated elastase-mediated IL-8
      production, it did not significantly influence the effect of proteinase 3. Both
      proteinase 3-and elastase-mediated production of IL-8 was inhibited by
      cycloheximide, indicating de novo synthesis. This was supported by the finding of
      increased IL-8 mRNA levels in proteinase 3-treated human umbilical vein
      endothelial cells by using Northern blot analysis. Taken together, the neutrophil
      lysosomal enzymes proteinase 3 and human neutrophil elastase may contribute to a
      self-perpetuating process of neutrophil recruitment in acute inflammation by
      increasing de novo synthesis of IL-8 by endothelial cells. The studies presented
      here also show that proteinase 3 mediates its effect independently of its
      enzymatic activity, indicating a hitherto unknown mode of action on endothelial
      cells.

PMID- 8738805
TI  - Identification of 17 mutations in ten exons in the COL4A5 collagen gene, but no
      mutations found in four exons in COL4A6: a study of 250 patients with hematuria
      and suspected of having Alport syndrome.
AB  - Conditions for polymerase chain-reaction amplification of ten exon regions (Exons
      3, 7, 11 through 13, and 15 through 19) of the collagen COL4A5 gene and four exon
      regions (Exons 2, and 12 through 14) of the COL4A6 gene were sequenced and
      established in this study. These Type IV collagen genes contain 51 and 48 exons,
      respectively. The sequences of these exons were determined in the two genes in
      250 male patients with hematuria and suspected Alport syndrome. Seventeen
      mutations were found in nine of the ten exons studied in the COL4A5 gene in 17
      patients, whereas no mutations were identified in COL4A6. One mutation was
      identical in two patients known to be unrelated. The results indicate that
      mutations in COL4A5 that leading to renal failure are more frequent than those
      involved in classic Alport syndrome, and also that mutations in COL4A6 are not
      likely to cause this disease. Furthermore, mutations in COL4A5 are distributed
      quite randomly and no "hot spots" were found.

PMID- 8738806
TI  - Effect of recombinant human insulin-like growth factor-1 on the inflammatory
      response to acute renal injury.
AB  - Renal ischemic injury evokes an inflammatory response with increased cytokine and
      major histocompatibility complex (MHC) expression and a mild interstitial
      infiltrate. This "injury response" could contribute to the tendency of
      ischemically injured renal transplants to reject. The studies presented here
      evaluated the ability of recombinant human insulin-like growth factor-1 (rhlGF-1)
      given after renal injury to prevent renal inflammation. The left renal pedicle of
      CBA and BALB/c mice was clamped for 60 min, and rhlGF-1 (25, 50, 100 micrograms)
      was administered sc at 2, 24, 48, 72, and 96 h after reflow. Cytokine and MHC
      expression was monitored in the injured kidney, compared with the contralateral
      kidney. In untreated mice, a single episode of injury induced the expression of
      MHC mRNA and products and tumor necrosis factor-alpha (TNF-alpha) mRNA, and
      depressed preproepidermal growth factor (ppEGF) mRNA, for up to 5 wk. With
      immunohistology, epithelial Class I and II MHC expression was shown to be
      increased for 2 wk, and Class II positive interstitial cells were shown to be
      increased for up to 5 wk. The ischemically injured kidneys from mice treated with
      rhlGF-1 and examined at 5 days showed a dose-dependent normalization of all of
      the changes of the injury response. This included prevention of the increased
      expression of MHC and cytokines and the Class II positive interstitial cells, and
      restoration of ppEGF mRNA. Thus the complex and long-lasting increase in
      proinflammatory cytokines and MHC expression that follow renal ischemia can be
      interrupted by treatment with rhlGF-1 beginning 2 h after the injury. This
      therapy may have applications to the injury response in renal transplants.

PMID- 8738807
TI  - Modulation of renal kallikrein production by dietary protein in streptozotocin
      induced diabetic rats.
AB  - Renal kallikrein levels and excretion rates are increased in insulin-treated
      diabetic rats with hyperfiltration, and inhibition of kallikrein or blockade of
      kinin receptors reduces GFR and RPF. In contrast, insulin-deprived severely (SD)
      diabetic rats that display renal vasoconstriction show reduced levels and
      excretion rates of renal kallikrein. In these two models, dietary protein
      manipulation was utilized to study further the relationships between renal
      kallikrein and renal hemodynamic regulation. Insulin-deprived SD and insulin
      treated moderately diabetic (MD) rats were fed a low (9%), normal (25%), and a
      high (50%) protein diet. In SD rats fed the 50% protein diet, GFR, RPF, and
      kallikrein excretion rate were increased compared with SD rats fed the 25%
      protein diet (GFR, 2.66 +/- 0.16 versus 1.74 +/- 0.30 mL/min; RPF, 7.78 +/- 0.58
      versus 5.14 +/- 1.03 mL/min; total kallikrein, 248 +/- 24 versus 120 +/- 30
      micrograms/24 h, SD 50% versus SD 25%, respectively; P < 0.005). In MD rats fed
      the 9% protein diet, GFR, RPF, and kallikrein excretion rate were significantly
      reduced compared with MD 25% protein-fed rats (GFR, 1.54 +/- 0.07 versus 1.95 +/-
      0.09 mL/min; RPF, 5.58 +/- 0.35 versus 7.81 +/- 0.35 mL/min; total kallikrein,
      119 +/- 8.3 versus 219 +/- 15 micrograms/24 h, MD 9% versus MD 25%, respectively;
      P < 0.005). Protein restriction in normal nondiabetic rats resulted in a twofold
      decrease in kallikrein mRNA levels. These findings suggest that the renal
      hemodynamic response to dietary protein manipulation in diabetic rats could be
      mediated via changes in renal kallikrein-kinin system activity.

PMID- 8738808
TI  - Hypoalbuminemia, cardiac morbidity, and mortality in end-stage renal disease.
AB  - A cohort of 432 ESRD (261 hemodialysis and 171 peritoneal dialysis) patients was
      followed up prospectively for an average of 41 months. Baseline and annual
      demographic, clinical, and echocardiographic assessments were performed, as well
      as serial clinical and laboratory tests measured monthly while patients were on
      dialysis therapy. Among hemodialysis patients, after adjustment was made for age,
      diabetes, and ischemic heart disease, as well as hemoglobin and blood pressure
      levels measured serially, a 10-g/L fall in mean serum albumin level was
      independently associated with the the development of de novo (relative risk [RR],
      2.22; P = 0.001) and recurrent cardiac failure (RR, 3.84; P = 0.003), de novo
      (RR, 5.29; P = 0.001) and recurrent ischemic heart disease (RR, 4.24; P = 0.005),
      cardiac mortality (RR, 5.60; P = 0.001), and overall mortality (RR, 4.33; P <
      0.001). Among peritoneal dialysis patients, a 10-g/L fall in mean serum albumin
      level was independently associated with the progression of left ventricular
      dilation as seen on follow-up echocardiography (beta, 13.4 mL/m2; P = 0.014), the
      development of de novo cardiac failure (RR, 4.16; P = 0.003), and overall
      mortality (RR, 2.06; P < 0.001). Hypoalbuminemia, a major adverse prognostic
      factor in dialysis patients, is strongly associated with cardiac disease.

PMID- 8738809
TI  - Dialysis adequacy and nutrition determine prognosis in continuous ambulatory
      peritoneal dialysis patients.
AB  - Peritoneal membrane function was assessed in patients undergoing continuous
      ambulatory peritoneal dialysis (CAPD) using parameters derived from urea kinetic
      modeling and the peritoneal equilibration test (PET). Their relationships with
      other nutritional markers and overall morbidity were determined. Data regarding
      the patients' nutritional status as determined by total body nitrogen (TBN)
      measurements, hospital admissions, and infectious complications within the last
      12 months were reviewed. Total dialysate clearance (Kt/V) delivered was highly
      dependent on residual renal function (P < 0.0001). Kt/V derived from peritoneal
      clearance diminished with increasing age (P < 0.05). A higher delivered total
      Kt/V was associated with higher normalized protein catabolic rates (P < 0.002),
      which in turn were associated with improved TBN (P < 0.05). Hospital admissions
      decreased with improved normalized protein catabolic rates (P < 0.05), and higher
      serum albumin and total protein levels (P < 0.01 and P < 0.002, respectively).
      Infectious complications correlated positively with time on dialysis (P < 0.01),
      and correlated negatively with TBN measurements (P = 0.05). No correlations were
      found between infectious complications and serum albumin level or peritoneal
      protein loss. However, the total duration of hospitalization was shortened with
      higher serum albumin and total protein levels (P < 0.0001 and P < 0.002,
      respectively). Although Kt/V determinations did not correlate with clearances
      determined by the PET, the PET-determined creatinine transport rate correlated
      with TBN (P < 0.05) but not with infectious complications. In conclusion,
      nutritional parameters correlate with outcome on continuous ambulatory peritoneal
      dialysis. An integral relationship exists between nutritional status and dialysis
      delivery, which is best assessed by urea kinetic modeling.

PMID- 8738810
TI  - Measurement of residual renal function in patients treated with continuous
      ambulatory peritoneal dialysis.
AB  - Renal function contributes markedly to the adequacy of continuous ambulatory
      peritoneal dialysis (CAPD). The best way to measure it in clinical practice has
      not been established. Ten stable CAPD patients with residual renal function were
      investigated to compare the GFR measured as inulin clearance (Cli) with the
      creatinine clearance (Clc), the urea clearance (Clu), and with 0.5(Clc + Clu).
      Thereafter, an analysis of whether the administration of cimetidine could improve
      the accuracy of these clearances was performed. Two clearance periods (CP) of 24
      h were investigated. During CP-2, patients received 400 mg cimetidine twice
      daily, for a total dose of 1200 mg. Two h before the urine and dialysate
      collection period, inulin was administered iv. Calculations were done for each CP
      for Cli, Clc, Clu, Clc-Cli, the Clc/Cli ratio, and the tubular secretion of
      creatinine (TSc). No differences between CP-1 and CP-2 were present for urinary
      excretion of volume and solutes, and clearance rates of inulin and urea. The
      median TSc decreased from 0.71 mumol/min (range, -0.24 to 5.90) in CP-1 to 0.30
      mumol/min (range, -0.18 to 0.64) in CP-2 (P < 0.05). Therefore, the median ratio
      of Clc/Cli decreased from 1.23 (range, 0.87 to 2.20) in CP-1 to 1.11 (range, 0.95
      to 1.51) in CP-2 (P < 0.05). The median overestimation of the Cli in CP-1 by the
      Clc was 0.90 mL/min (range, -0.28 to 3.80) and by the 0.5(Clc + Clu) was 0.30
      (range, -0.67 to 1.52). The median overestimation of Cli during cimetidine
      treatment in CP-2 was 0.43 mL/min (range, -0.21 to 1.20). The range, in
      differences between Cli and Clc, in CP-2 was smaller than that between Cli and
      0.5(Clc + Clu) in CP-1. The difference between the clearance rate of inulin and
      creatinine or the combined clearance rate of urea and creatinine was not
      influenced by the magnitude of the average GFR. It can be concluded that the
      administration of cimetidine improved the accuracy of measuring the GFR with the
      Clc in CAPD patients.

PMID- 8738811
TI  - Relative risk and economic consequences of inpatient care among patients with
      renal failure.
AB  - During the final phases of chronic renal disease, inpatient care comprises an
      enormous share of morbidity and direct medical costs. Using an attributable risk
      methodology, this study calculated inpatient resource utilization and associated
      costs for chronic renal failure (CRF) and ESRD. A national hospital survey was
      used to identify the 348,962 hospitalizations for patients with renal failure in
      1991. Among persons under the age of 65, pre-ESRD CRF patients had the same
      number of hospitalizations (nearly 75,000) as ESRD patients. Age-adjusted
      relative risk calculations indicate that patients with renal failure experience
      greater inpatient morbidity compared with other populations with chronic,
      progressive diseases. For example, compared with persons with diabetes, ischemic
      heart disease, hypertension, and emphysema, renal patients were at significantly
      higher risk of hospitalization for congestive heart failure, pneumonia, sepsis,
      electrolyte disorders, and gastrointestinal hemorrhage. Overall, renal failure
      patients were ten times more likely to be hospitalized (relative risk, 10.0; 95%
      confidence interval, 10.00 to 10.04) and, on average, were hospitalized nearly 1
      day longer (P < 0.01) compared with the non-renal failure population in 1991. As
      a result, the economic consequences of inpatient care for the treatment of renal
      failure were enormous. In 1991, 222,827 hospitalizations, 1.5 million days of
      inpatient care, and $2.2 billion were attributable to renal failure. Further
      studies that examine other components of direct medical costs (e.g., long-term
      care, outpatient care, and pharmaceuticals) as well as indirect costs associated
      with the treatment and care of renal failure patients are warranted.

PMID- 8738812
TI  - The effects of recombinant human erythropoietin on functional health and well
      being in chronic dialysis patients.
AB  - As a component of the open-label, multicenter National Cooperative Recombinant
      Human Erythropoietin (Epo) Study, the health-related quality-of-life effects of
      Epo therapy were assessed in 484 dialysis patients who had not previously been
      treated with Epo therapy (New-to-Epo) and 520 dialysis patients who were already
      receiving Epo therapy at the time of study enrollment (Old-to-Epo). Using scales
      from the Medical Outcomes Study 36-item Short Form Health Survey (SF-36), health
      related quality of life was assessed on study enrollment (baseline) and at an
      average of 99 days follow-up. At baseline, SF-36 scores for Old- and New-to-Epo
      patients were well below those observed in the general population, reflecting
      substantial impairments in functional status and well-being among patients with
      chronic renal failure. Significant improvements from baseline to follow-up were
      observed among New-to-Epo patients in vitality, physical functioning, social
      functioning, mental health, looking after the home, social life, hobbies, and
      satisfaction with sexual activity (P < 0.05 for each). The mean improvements in
      hematocrit values among New-to-Epo and Old-to Epo patients were 4.6 and 0.3,
      respectively. At the time of follow-up, SF-36 scores for New-to-Epo patients were
      comparable with those observed among Old-to-Epo patients, whose scores did not
      change significantly from baseline to follow-up. Analysis of the relationship
      between Epo therapy, hematocrit values, and health-related quality of life
      suggest that some of the beneficial quality-of-life effects of Epo are mediated
      through a change in hematocrit level.

PMID- 8738813
TI  - Effects of recombinant human erythropoietin on porphyrin metabolism in uremic
      patients on hemodialysis.
AB  - Recombinant human erythropoietin (r-HuEPO) is being successfully used for the
      treatment of uremic anemia. Several abnormalities of heme biosynthetic pathway
      have been described in patients with end-stage renal failure. In this condition,
      the activity of erythrocyte porphobilinogen deaminase has been found to be
      slightly increased. If this enzyme were to be the key enzyme in erythroid heme
      regulation, its activity would be increased to an even greater degree during the
      correction of uremic anemia. To assess this hypothesis, this study followed the
      variations of this and other parameters of porphyrin metabolism over 12 months of
      erythropoietin therapy in eight patients with nephrogenic anemia who underwent
      hemodialysis. By the first month of therapy, an increase of the previously
      depressed erythrocyte activity of aminolevulinate dehydratase was already
      evident, in coincidence with a nonsignificant increase of the reticulocyte count.
      The activity of this enzyme reached its maximal level by Month 3, and did not
      change up to Month 10. The porphobilinogen deaminase hyperactivity normalized at
      Month 4. By Month 12, in coincidence with the reduction of erythropoietin doses,
      the maximal levels of erythrocyte protoporphyrin, and the decrease in
      aminolevulinate dehydratase activity, the porphobilinogen deaminase values
      started to increase once again. In conclusion, the administration of r-HuEPO to
      hemodialyzed patients induced transient normalization of the previously observed
      porphyrin metabolism abnormalities. However, erythrocyte porphobilinogen
      deaminase activity did not rise concomitantly with the increase in hematocrit or
      hemoglobin values, but it did diminish during treatment. Therefore,
      porphobilinogen deaminase did not behave as a controlling enzyme in heme
      synthesis during the r-HuEPO-induced correction of uremic anemia.

PMID- 8738814
TI  - Equations for normalized protein catabolic rate based on two-point modeling of
      hemodialysis urea kinetics.
AB  - The normalized protein catabolic rate (PCRn) can be calculated from predialysis
      and postdialysis BUN measurements in patients receiving intermittent dialysis.
      This measure of net protein catabolism, adjusted for body size, is a useful
      clinical measure of nutrition that correlates with patient outcome and, in
      patients who are in nitrogen balance, is a reasonable estimate of dietary protein
      intake. Whereas simplified formulae that estimate the per-treatment dose of
      hemodialysis, expressed as Kt/Vurea (Kt/V), are in common use, simplified methods
      for determining PCRn have only recently appeared. In the study presented here,
      equations were derived for calculating PCRn from the predialysis BUN and Kt/V.
      The equations were of the general form: PCRn = C0/(a + bKt/V + c/(Kt/NLL)) +
      0.168, where Co is the predialysis BUN in mg/dL. Three sets of coefficients were
      developed for patients dialyzed thrice weekly: one for patients dialyzed after
      the long interval at the beginning of the week, one for patients dialyzed at
      midweek, and the third for patients dialyzed at the end of the week. Two similar
      sets of coefficients were developed for patients dialyzed twice weekly. For
      patients with remaining function in the native kidney remnant, equations were
      developed and refined for upgrading PCRn by adjusting C0 upward. The equations
      were validated by comparing the calculated PCRn with PCRn determined by a formal
      iterative model of urea kinetics in a series of 119 dialyses in 51 patients
      dialyzed thrice weekly (r = 0.9952; mean absolute error, 1.97 +/- 1.39%) and in a
      series of 71 dialyses in 25 patients dialyzed twice weekly (r = 0.9956; mean
      absolute error, 2.17 +/- 1.56%). These simple yet accurate equations should be
      useful in epidemiologic studies or in clinical laboratories where limited data
      are available for each patient or when iterative computer techniques cannot be
      applied.

PMID- 8738815
TI  - A logistic-regression model provides novel guidelines to maximize the anti-acute
      rejection properties of cyclosporine with a minimum of toxicity.
AB  - Although cyclosporine has become the mainstay of immunosuppression in organ
      transplantation, there is still no consensus on the criteria to optimize its anti
      rejection activity with minimum toxicity. A clear and objective definition of
      target cyclosporine trough levels at different times from renal transplantation
      is still lacking, primarily because of the lack of a model correlating
      cyclosporine levels with probability of rejection or toxicity. In this study,
      logistic-regression model was developed that was applied to data collected
      retrospectively from two postoperative periods, i.e., Days 0 to 9 and 10 to 30,
      in 135 consecutive cadaveric renal transplant recipients, for a total of 1851
      determinations. Only minimum and maximum trough levels were considered for each
      period. Concentration-response curves were estimated for Days 0 to 9 (P = 0.0001
      for efficacy and P = 0.028 for toxicity) and for Days 10 to 30 (P = 0.015 for
      efficacy and P = 0.037 for toxicity). Therapeutic intervals of 330 to 430 ng/mL
      (parent compound in whole blood) for Days 0 to 9 and 260 to 390 ng/mL for Days 10
      to 30 predicted an incidence of acute rejection of 22% and 12%, respectively,
      with a reasonably low toxicity that primarily consisted of elevation of serum
      aminotransferases.

PMID- 8738816
TI  - Randomized study with cyclosporine in kidney transplantation: 10-year follow-up.
AB  - This study presents the 10-yr follow-up results of a multicenter controlled trial
      on 108 recipients of cadaveric renal transplantation, randomized to receive
      cyclosporine (N = 55) or azathioprine (N = 53), both in combination with
      steroids. The 10-yr patient survival rate was 89% in the cyclosporine group and
      83% in the azathioprine group (P = not significant [NS]); the 10-yr graft
      survival was 56% and 35%, respectively (log-rank test, P = 0.009). The half-life
      of grafts functioning after 1 yr was 15.4 +/- 3.9 versus 10.6 +/- 3.6, P = NS).
      The rate of early rejection in the cyclosporine group was significantly lower
      than that in the azathioprine group (0.30 versus 1.4, P < 0.01). Although the
      mean creatinine clearance rate was always higher in the azathioprine group, the
      decline in graft function from the first to the tenth yr was not significantly
      different between the two groups (-13.0 +/- 16.4 versus -12.3 +/- 19 mL/min, P =
      NS). In cadaveric renal transplantation, cyclosporine allows better graft
      survival than azathioprine, not only in the short term but also in the long term,
      with similar attrition of graft function for up to 10 yr.

PMID- 8738817
TI  - Renal transplantation relieves the symptoms but does not reverse beta 2
      microglobulin amyloidosis.
AB  - Renal transplantation is considered to be the treatment of choice of dialysis
      related beta 2-microglobulin amyloidosis (DRA), as it provides near-normal serum
      levels of beta 2-microglobulin and obviates the need for dialysis. However, the
      long-term outcome of DRA after transplantation has not been fully assessed, and
      its evolution after transplant failure has not been reported. This study examined
      17 patients with histologically confirmed DRA who underwent kidney
      transplantation and had a dialysis-free follow-up period in excess of 1 yr.
      Immunosuppressive treatment included low-dose prednisolone, cyclosporine, and/or
      azathioprine. Symptoms related to DRA were sought at every outpatient visit, and
      bone x-rays were performed at time of transplantation and annually thereafter.
      The number and size of the bone cysts were determined. Most of the DRA symptoms,
      and particularly shoulder stiffness, disappeared within the first wk after
      transplantation and this persisted throughout the transplant follow-up period
      (58.5 +/- 9 months). However, the number of bone cysts remained remarkably
      constant even in those patients with still-functioning grafts (12 +/- 7.5 and
      12.1 +/- 7.7, before and at last transplantation follow-up examination,
      respectively). Beta 2-microglobulin amyloid was found to be present in one
      patient operated on for hip fracture 2 yr after receiving a well-functioning
      transplant. Seven patients experienced graft failure and returned to dialysis
      after 47 +/- 39 months of transplantation. Severe DRA symptoms reappeared
      strikingly early after resuming hemodialysis, and five out of the seven patients
      required surgery for carpal tunnel syndrome, three of them within the first yr
      (mean, 17 +/- 12 months). The number of cysts significantly increased from 17 +/-
      11 to 21 +/- 11 during the second dialysis period. These findings provide further
      evidence suggesting that although the clinical expression of DRA is arrested
      during transplantation, the anatomical lesions and the pathological processes
      underlying it are unlikely to be reversed.

PMID- 8738818
TI  - Evidence in hyponatremia related to inappropriate secretion of ADH that V1
      receptor stimulation contributes to the increase in renal uric acid clearance.
AB  - In hyponatremia related to syndrome of inappropriate antidiuretic hormone
      (SIADH), hypouricemia is explained primarily by the high uric acid clearance rate
      that results from the decrease in tubular uric acid reabsorption. This
      modification of tubular handling of uric acid is considered to be induced by the
      increase in the "effective vascular volume". This study was designed to determine
      if V1-receptor stimulation participates in the development of a high uric acid
      clearance rate as in SIADH, in which the antidiuretic hormone acts on V1 and V2
      receptors. Therefore, the urate clearance rate was measured in seven volunteers
      with 1-desamino-8-D-arginine vasopressin (dDAVP)-induced hyponatremia, with dDVAP
      stimulating exclusively the V2 receptors (Group I), and in six patients with
      SIADH (Group II) during both normo- and hyponatremia. As expected, in both
      groups, the serum uric acid concentration decreased during hyponatremia, but did
      so to a larger extent in the patients with SIADH (-53% versus -29%, P < 0.02).
      Despite similar levels of hyponatremia (126 +/- 5 mmol/L and 125 +/- 5.5 mmol/L),
      of hypoproteinemia (64 +/- 5 g/L and 63 +/- 5 g/L) and of salt excretion (FENa,
      0.66 +/- 0.28% and 0.73 +/- 0.25%), the urate clearance (8.3 +/- 3.3 mL/min) and
      the fractional excretion of filtered uric acid (5.7 +/- 2%) in Group I were not
      significantly different during hyponatremia than during normonatremia (6.4 +/-
      1.5 mL/min and 5.4 +/- 0.9%). On the other hand, in Group II, both parameters
      were increased (17.8 +/- 2.9 mL/min and 19.6 +/- 5.3%; P < 0.001) and both values
      were higher than in the dDAVP-induced hyponatremia (P < 0.01). Additionally, the
      administration of a potent V1-receptor agonist (triglycyl-lysine-vasopressin) in
      a patient with central diabetes insipidus with preexisting dDAVP-induced
      hyponatremia produced a rapid increase of urate clearance. Because dDAVP acts
      only on the V2 receptors, these data suggest that the higher urate clearance
      observed during hyponatremia related to SIADH is not only the consequence of an
      increased "effective vascular volume," but that V1-receptor stimulation also
      contributes to it, by a mechanism that remains to be determined.

PMID- 8738819
TI  - Oral ciprofloxacin for the first-phase treatment of peritonitis associated with
      continuous ambulatory peritoneal dialysis.

PMID- 8738820
TI  - Surgical management of lung metastases: selection factors and results.
AB  - Lung parenchyma is the most common site of metastases from either carcinomas or
      sarcomas. Depending on the status of the original primary, resection of lung
      metastases may be curative. Multiple variables must be considered when deciding
      whether or not to operate on a patient with metastatic disease to the lung: The
      primary site must be evaluated; the lungs should be the only site of metastatic
      disease; the patient must be able to withstand the resection; and total removal
      of all disease must be possible. Other characteristics may be important to
      consider, such as the number of nodules and disease-free interval, and these
      factors may vary from histology to histology. However, if feasible, surgical
      resection remains the most important treatment modality for patients with
      pulmonary metastases.

PMID- 8738821
TI  - Neoprobe reports initial results of multicenter trials of colorectal cancer
      detection system.

PMID- 8738822
TI  - Colorectal cancer screening is cost-effective, OTA study shows.

PMID- 8738823
TI  - Clinical trials renew interest in old drug for children with leukemia.

PMID- 8738824
TI  - Hematologic complications of HIV infection.
AB  - Hematologic complications of HIV disease are commonly encountered by physicians
      and other health-care workers caring for patients infected with this virus.
      Ineffective hematopoiesis, infiltrative diseases of the bone marrow, nutritional
      deficiencies, peripheral destruction of blood cells secondary to splenomegaly or
      immune dysregulation, and drug effects all contribute to the variety of
      hematologic abnormalities seen in these patients. This review explores the causes
      of isolated or trilineage cytopenias and coagulopathies; the utility of bone
      marrow biopsy examination; and the role of colony-stimulating factors as
      therapeutic agents in patients with HIV disease.

PMID- 8738825
TI  - Management of radiation-induced brachial plexus neuropathy. Royal College
      Radiologists.
AB  - This report was prepared by a special committee of the Royal College of
      Radiologists. It provides a British perspective on how to manage this potential
      complication of breast irradiation. Portions of the report are summarized or,
      where indicated, reproduced in their entirety, with the permission of the
      College.

PMID- 8738826
TI  - Clinical trial to evaluate antitumor activity of epidermal growth factor in
      breast cancer.

PMID- 8738827
TI  - AIDS activists meet to establish community-based standards for life insurance
      settlements.

PMID- 8738828
TI  - Long-term survival of children with brain tumors.
AB  - Outcome is described for 1,034 children who received radiation treatment in the
      management of a brain tumor at the University of Toronto Institutions from 1958
      to 1995. The 5-, 10-, 20-, and 30-year relapse-free (or progression-free)
      survival rates were 47%, 45%, 44%, and 44%, respectively, whereas the
      corresponding overall survival rates were 52%, 44%, 38%, and 30%. Second
      malignant tumors became an important cause of death over time, with cumulative
      incidences of 2.5%, 13%, and 19% at 10, 20, and 30 years, respectively. The 5
      year survival rate after the diagnosis of a second malignant tumor was 58%. In
      general, high-grade tumors, eg, high-grade astrocytomas or brainstem tumors, had
      a poor 20-year survival rate (18%), compared with low-grade tumors (39% to 47%).
      Despite improvements in imaging, neurosurgical technique, and radiation
      treatment, children treated during the last 20 years did not have a significantly
      improved outcome when compared to children treated earlier.

PMID- 8738829
TI  - Clinical trials referral resource. Clinical trials using bryostatin-1.

PMID- 8738830
TI  - Management of benign and aggressive intracranial meningiomas.
AB  - Usually considered benign tumors, meningiomas can display aggressive behavior
      characterized by multiple recurrences and invasion of the brain, dura, and
      adjacent bone. The aggressive or malignant phenotype is difficult to characterize
      due to the broad spectrum of behaviors exhibited by meningiomas. Recent
      classification schemes based on features of anaplasia rather than histopathology
      have been used successfully to identify meningiomas that exhibit features of the
      aggressive phenotype. Some such tumors can be identified preoperatively by
      radiographic characteristics. Surgery is the cornerstone of treatment for all
      types of meningiomas. Conventional radiation therapy is beneficial for patients
      with recurrent (or incompletely resected) benign meningiomas and is recommended
      for those with aggressive and malignant meningiomas. Stereotactic radiation and
      interstitial brachytherapy are useful in some refractory or recurrent
      meningiomas. Traditional chemotherapeutic agents are not very effective against
      meningiomas, but hormonal manipulation is under study for patients with
      inoperable tumors or those who are medically unsuitable for surgery.

PMID- 8738831
TI  - Marital arguments lead to weakened immune system in older couples.

PMID- 8738832
TI  - Site-directed estrogen receptor antibodies stabilize 4-hydroxytamoxifen ligand,
      but not estradiol, and indicate ligand-specific differences in the recognition of
      estrogen response element DNA in vitro.
AB  - Conformational differences between type I antiestrogen-liganded estrogen receptor
      and estradiol (E2)-liganded estrogen receptor (ER) are thought to be responsible
      for differentiating agonist versus antagonist ER activity at individual genes. To
      examine the impact of ER ligand on estrogen-response element (ERE) binding
      kinetics and receptor conformation, we quantitated the effect of site-directed,
      ER-specific antibodies raised against synthetic peptides corresponding to the DNA
      binding domain of human ER on ER-ERE binding in vitro. Although 4
      hydroxytamoxifen-liganded-ER (4-OHT-ER) and E2-ER bind a consensus ERE with equal
      high affinity, the stoichiometry of 4-OHT-ER-ERE binding at saturation is
      approximately 50% lower than that of E2-ER binding to all ERE sequences tested.
      In contrast, the ERE binding stoichiometry of tamoxifen aziridine-liganded ER
      (TAz-ER) is identical to that of E2-ER: one receptor dimer bound per ERE. The
      difference in binding stoichiometry is caused by dissociation of one molecule of
      4-OHT from the ER as the dimeric receptor binds DNA. Addition of low
      concentrations of ER-specific polyclonal antibodies AT3A or AT3B prevented 4-OHT
      ligand dissociation, yielding an increase in specific 4-OHT-ER-ERE binding to a
      level equal to that of E2-ER- or TAz-ER-ERE binding. However, higher amounts of
      AT3A or AT3B inhibited specific ERE binding of both 4-OHT- and E2-ER. We conclude
      that differences in ER conformation when liganded with 4-OHT versus E2 are
      revealed by these antibodies and that such differences in receptor conformation
      may influence subsequent interaction of the receptor with other proteins
      necessary for transactivation.

PMID- 8738833
TI  - Differential behavior of (25R)-5,6-epoxyspirostan-22 alpha-O-3 beta-ol and (25R)
      5,6-epoxyspirostan-22 alpha-O-3 beta, 4 beta-diol toward Dowex.
AB  - The acid-catalyzed hydrolytic cleavage of the 5,6-epoxyspirostane derivatives by
      the cation exchange resin Dowex 50W X8 has been exploited with the goal of
      developing synthetic protocols toward 3,4,5,6-polyhydroxyspirostane analogs that
      can serve as intermediates to potential biologically active compounds. Whereas
      the diastereomers (25R)-5 alpha, 6 alpha-epoxyspirostan-22 alpha-O-3 beta-ol and
      (25R)-5 beta, 6 beta-epoxyspirostan-22 alpha-O-3 beta-ol yield two products,
      (25R)-6 beta-methoxyspirostan-22 alpha-O-3 beta, 5 alpha-diol and (25R)-spirostan
      22 alpha-O-3 beta, 5 alpha, 6 beta-triol on Dowex treatment in water-methanol,
      the alpha- and beta-diastereomers of the 5,6-epoxy derivative of 3 beta, 4 beta
      diol provide a single product, (25R)-3 beta, 6 beta-dihydroxy-5 alpha-spirostan-4
      one, in good yields. The structures of these products have been confirmed using
      1H NMR, 13C NMR, and 1H-1H J-correlated spectroscopies. Multifunctional product
      formation suggests tremendous utility of Dowex in steroid synthesis. The product
      formation has been rationalized on the basis of differential conformational
      constraints of the A/B rings of the different epoxides in directing the reaction
      course. The reaction shows an interesting example of stereoelectronic effect of a
      single hydroxy group in discriminating solvent participation.

PMID- 8738834
TI  - Synthesis of N-acetylcysteine conjugates of catechol estrogens.
AB  - The synthesis of N-acetylcysteine conjugates of 2-hydroxyestrone (2-OHE1) and 4
      hydroxyestrone (4-OHE1) is described. The reaction of estrone 2,3-quinone with N
      acetylcysteine provided 2-OHE1 and its C-4 and C-1 thioether conjugates in a
      ratio of 1:1, while estrone 3,4-quinone with N-acetylcysteine gave 4-OHE1 and its
      C-2 thioether conjugate as a sole product. Their structures were characterized by
      inspection of NMR spectra, chemical derivatization (methylation and acetylation),
      and comparison with the reactivity of 4-bromoestrone 2,3-quinone or 2
      bromoestrone 3,4-quinone toward N-acetylcysteine.

PMID- 8738835
TI  - Heterocyclic steroids: synthesis of steroidal selena, tellura, and thialactones
      of estrane series.
AB  - A successful approach in the synthesis of 3 beta-acetoxy-17a-selena-D-homo
      1,3,5(10)-estratrien-17 -one (5), 3 beta-acetoxy-17a tellura-D-homo-1,3,5(10)
      estratrien-17-one (6), and 3 beta-acetoxy-17a-thia-D-homo-1,3,5(10)-estratrien-17
      one (7) was achieved from 3 beta-acetoxy-1,3,5(10)-estratrien-17-one (1). The
      Baeyer-Villiger reaction of 3 beta-acetoxy-1,3,5(10)-estratrien-17-one (1) with
      perbenzoic acid afforded 3 beta-acetoxy-17a-oxa-D-homo-1,3,5(10)-estratrien-17
      one (2), which on reaction with hydrobromic acid gave 3 beta-acetoxy-seco-13
      bromo-1,3,5(10)-estratrien-16-oic acid (3). Treatment of bromo acid (3) with
      thionyl chloride gave 3 beta-acetoxy-seco-13-bromo-1,3,5(10)-estratrien-17 acid
      chloride (4), whose reaction with Se and Te in the presence of sodium borohydride
      gave the desired products 5 and 6. Reaction of 3 beta-acetoxy-seco-13-bromo
      1,3,5(10)-estratrien-17 acid chloride (4) with sodium sulfide gave the thia
      lactone derivative (7).

PMID- 8738836
TI  - In vitro antioxidant effects of estrogens with a hindered 3-OH function on the
      copper-induced oxidation of low density lipoprotein.
AB  - Estrogens with some bulky alkyl substituents in both the 2- and 4-positions have
      been synthesized and evaluated for the ability to inhibit the in vitro oxidation
      of low density lipoprotein as determined by the thiobarbituric reactive
      substances method. The present compounds with bulky groups in either the 2- or
      the 4-position (but not both the 2- and 4-) were especially effective as
      antioxidants, having IC50 values lower than either estradiol or probucol;
      however, they do not bind to the estrogen receptor with any great affinities (RBA
      < 0.1 versus estradiol). This separation of antioxidant efficacy from
      estrogenicity may allow these compounds to serve as useful probes for
      ascertaining the relative importance of these effects in the cardioprotective
      role played by estrogens.

PMID- 8738837
TI  - Altering culture conditions reveals strain-related differences in activity and
      immunoreactive isoforms of 3 beta-hydroxysteroid dehydrogenase-isomerase in mouse
      Leydig cells.
AB  - We previously reported that 3 beta-hydroxysteroid dehydrogenase-isomerase (3 beta
      HSD) activity is higher in Leydig cells from C57BL/6J mice than those from
      C3H/HeJ mice. This study examines whether the differences in 3 beta HSD activity
      in Leydig cells from the two strains of mice are due to the expression of
      different 3 beta HSD isoforms and if a specific isoform corresponds with the
      amount of 3 beta HSD activity under various culture conditions. Leydig cells were
      plated in Waymouth's +15% horse serum (HS) medium. Some cultures were terminated
      24 h later after plating (day 1) and assayed for 3 beta HSD activity or
      immunoreactivity. The remaining cultures were maintained in HS or changed to
      serum-free medium. We demonstrate for the first time that two 3 beta HSD
      immunoreactive isoforms are expressed in freshly isolated Leydig cells and those
      cultured for 1 day. The same two 3 beta HSD isoforms are detectable in both
      strains. Thus, the previously reported strain-related differences in 3 beta HSD
      activity are not due to the expression of different isoforms. When cultured for 8
      days, the higher molecular weight 3 beta HSD immunoreactive band is no longer
      detectable in Leydig cells from either strain. When maintained in HS, 3 beta HSD
      activity in C57BL/6J Leydig cells decreases significantly by day 8, while 3 beta
      HSD activity in C3H/HeJ Leydig cells does not change through day 8. When Leydig
      cells were cultured in serum-free medium, 3 beta HSD activity is maintained in
      cultured Leydig cells from C57BL/6J and significantly increases in C3H/HeJ 3 beta
      HSD by day 8. These data suggest that HS has a strain-specific inhibitory effect
      on 3 beta HSD activity, causing a significant decrease in C57BL/6J 3 beta HSD
      activity and preventing an increase in C3H/HeJ. Densitometric analysis reveals a
      correspondence between changes in 3 beta HSD activity and the lower molecular
      weight isoform but not the higher molecular weight isoform. Treatment with cAMP
      induces the immunoreactive mass of the lower molecular isoform but not the higher
      molecular isoform of 3 beta HSD. Currently, it is unclear what the function of
      the higher molecular weight 3 beta HSD isoform is in mouse Leydig cells.

PMID- 8738838
TI  - Endothelin-1-induced incorporation of cholesterol into rat adrenals.
AB  - The effect of endothelin-1 (ET-1) on cholesterol uptake by adrenal cortex was
      evaluated through several experimental approaches: infusion of ET-1 followed by
      measurement of endogenous cholesterol in excised adrenals; infusion of ET-1
      followed by tritiated cholesterol incorporation into adrenal quarters in vitro;
      coinfusion of ET-1 with tritiated cholesterol-enriched serum and determination of
      adrenal-associated radioactivity; and tritiated cholesterol incorporation in
      incubations of adrenal cells. In all cases ET-1 increased cholesterol uptake.
      Subcellular fractionation showed an ET-1-mediated augmentation in mitochondrial
      fraction. This increase was mediated by the subpopulation B of adrenal receptors
      for ET-1. In addition, ET-1 also increased cytochrome P450-SCC (side-chain
      cleavage) activity.

PMID- 8738839
TI  - Photoaffinity labeling of rat steroid 5 alpha-reductase (isozyme-1) by a
      benzophenone derivative of a 4-methyl-4-azasteroid.
AB  - [1,2-3H]N-4(Benzylbenzoyl)-3-oxo-4-aza-4-methyl-5 alpha-androstane-17 beta
      carboxamide ([3H]-4MABP) has been synthesized as a photoaffinity probe of the
      steroid-binding domain of rat steroid 5 alpha-reductase isozyme-1 (5 alpha R-1).
      Reversible binding of the probe to 5 alpha R-1 in microsomal preparations yielded
      a reversible dissociation constant (Kd) of -3 nM, whereas inhibition experiments
      indicated that the probe had a 50% inhibition concentration of 4.4 nM and was a
      competitive inhibitor of the enzyme (Ki approximately 3 nM) with respect to
      testosterone. SDS-PAGE analysis of microsomal, detergent-solubilized, and (6.5%)
      polyethylene glycol-precipitated fractions of 5 alpha R-I photolyzed with
      [3H]4MABP in the presence of NADPH showed that the radioactivity was incorporated
      into a single protein band with a mass of 26 kDa (apparent molecular weight of 5
      alpha R-1). UV photolysis was accompanied by an irreversible loss in enzyme
      activity, consistent with its covalent modification. Increasing the time of UV
      irradiation and concentration of [3H]4MABP indicated that the half-life and
      apparent Kd for its photo insertion were approximately 3 min and 7.5 nM,
      respectively. Photolysis in the presence of a 20-fold excess of N,N-diethyl-4-aza
      4-methyl-3-oxo-5 alpha-androstane-17 beta-carboxamide or the 3-carboxysteroid SKF
      105111 resulted in partial protection of 5 alpha R-1 from the probe, whereas
      minimal incorporation of radioactivity was observed in the absence of NADPH or in
      the presence of NADP+. The results indicate that [3H]4MABP is an effective probe
      of the steroid (D-ring) binding domain of 5 alpha R-1.

PMID- 8738840
TI  - beta-Lipotropin-stimulated adrenal steroid production.
AB  - The present study was undertaken to examine the mechanism whereby beta-lipotropin
      stimulates adrenal steroidogenesis. In guinea pig adrenal cells, beta-lipotropin
      (10(-8) M) increased basal steroid production 6-, 4-, and 5-fold for cortisol,
      androstenedione, and dehydroepiandrosterone (DHEA), respectively, whereas the
      corresponding responses to adrenocorticotropin (ACTH) (10(-9) M) were 12-, 8-,
      and 7-fold. The conversion of cholesterol to pregnenolone was studied in cells
      treated with trilostane, an inhibitor of 3 beta-hydroxysteroid delta 4-5
      isomerase. beta-Lipotropin (10(-10) and 10(-8) M) and ACTH (10(-9) M) stimulated
      pregnenolone production in trilostane-treated cells. The production of cortisol
      and androgens from precursor steroids was also studied in cells treated with
      aminoglutethimide, an inhibitor of cholesterol side chain cleavage, after
      addition of exogenous pregnenolone, 17-hydroxypregnenolone, progesterone, or
      DHEA. Neither ACTH nor beta-lipotropin stimulated cortisol, androstenedione, or
      DHEA production in the presence of exogenous precursors in aminoglutethimide
      treated cells. No inhibition of the beta-lipotropin- or ACTH-stimulated cortisol
      or androstenedione responses was demonstrated with the opioid receptor antagonist
      naloxone (10(-11) to 10(-5) M). The results suggest that beta-lipotropin
      stimulates steroidogenesis by acting on the conversion of cholesterol to
      pregnenolone and that its effects are not mediated via an opioid receptor but may
      be mediated via an ACTH receptor.

PMID- 8738841
TI  - Introduction: cephalosporin generations.

PMID- 8738842
TI  - The chemistry and structure-activity relationships of C3-quaternary ammonium
      cephem antibiotics.
AB  - The observation of a broad spectrum of antibacterial activity for cefpirome and
      for cefepime highlighted the benefits of combining a C3-quaternary ammonium
      substituent with the (Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido side
      chain at C7. The quaternary nitrogen imparts beta-lactamase stability and
      improves both the cell penetration and the pharmacokinetic properties of these
      antibiotics. A variety of different quaternary ammonium substituents have been
      added, successive alterations in the groups attached to nitrogen have extended
      the activity of the fourth generation compounds. A number of different methods
      for attaching the quaternary ammonium group have been established, including the
      direct linkage to the C3-methylene, linkage via a C3-thiomethylene and also
      linkage via an alkenyl bridge. A number of different strategies have been
      developed for the preparation of these derivatives and these have been collated
      in this review. The beta-lactamase stability of fourth generation cephalosporins
      can be attributed to the formation of a transiently stable modified acyl-enzyme.
      The extent to which the modified acyl-enzyme contributes to the beta-lactamase
      stability is very much dependent on the leaving ability (nucleofugacity) of the
      C3-substituent. The influence of the quaternary ammonium substituents, on the
      formation of the modified acyl-enzyme, will be discussed.

PMID- 8738843
TI  - Comparative affinities for penicillin-binding proteins of multipolar ionic
      amphoteric cephalosporins in gram-negative bacteria.
AB  - Chemical modification of the highly reactive 7-aminocephalosporanic acid has
      yielded many compounds with improved activities and expanded clinical spectra.
      Introduction of an alpha-oxyimino group in C-7 position has given rise to
      improved activity against Gram-negative bacteria as a consequence of the high
      affinity of compounds carrying this substituent for the essential penicillin
      binding protein (PBP) 3. The spectrum of activity of oxyimino cephalosporins has
      been further expanded by introduction of substituents with a quaternary nitrogen
      in C-3 position. These compounds have maintained their high affinity for the
      essential PBP 3, typical of the third generation cephalosporins and have acquired
      an improved ability to cross the outer membranes of Gram-negative bacteria. Among
      these compounds cefepime also exhibits high affinity for PBP 2, a very unusual
      property among cephalosporins.

PMID- 8738844
TI  - Antibacterial in vitro activity of fourth generation cephalosporins.
AB  - Cefpirome, cefepime and cefaclidine are distinguished by having a positively
      charged quaternary ammonium at carbon 3 of the dihydrothiazone ring. This confers
      the distinctive advantages of higher permeability across the outer membrane and
      low affinity for chromosomal cephalosporinases compared to the third generation
      cephalosporins which lack this quaternary ammonium moiety. These properties
      result in a marked advantage against resistant mutants of several species
      containing either derepressed class C chromosomal beta-lactamases or variant
      class A beta-lactamase. These unique properties have led to the suggestion that
      these compounds represent a "fourth generation" of cephalosporins.

PMID- 8738845
TI  - Bacterial resistance to cephalosporins as a function of outer membrane
      permeability and access to their target.
AB  - Resistance of Gram-negative bacteria to cephalosporins, as with other beta-lactam
      antibiotics, is a function of a combination of outer-membrane permeability,
      affinity and stability to beta-lactamases, and their activity against target
      sites (penicillin-binding proteins). Permeation through the outer-membrane is
      largely governed by the presence and properties of porins, which are water-filled
      channels facilitating the movement of hydrophilic molecules across the membrane.
      The properties of porins vary considerably between wild-type bacterial species,
      and their numbers (and hence the ability of a bacterial cell to exclude the
      antibiotic) may be reduced in strains with acquired resistance. In the case of
      cephalosporins, ability to cross the outer-membrane is related to physico
      chemical properties such as molecular size, hydrophobicity and the number and
      charge of ionised groups. Thus, for example, dianionic compounds have in general
      lower permeability rates than dipolar cephalosporins. These relationships are
      discussed in detail. The phenotypically expressed susceptibility of a particular
      bacterial strain to a cephalosporin is brought about by a dynamic combination of
      permeation, the ability of the agent to resist degradation or binding to the beta
      lactamases in the periplasmic space which act upon the relatively low
      concentration of cephalosporin present there, and target affinity. The interplay
      of these factors is discussed.

PMID- 8738846
TI  - Newer antipseudomonal cephalosporins.
AB  - The in vitro antipseudomonal activity of eight cephalosporins with alpha-oxyimino
      aminothiazolyl or aminothiadiazolyl group in the 7 beta-side chain and the
      quaternary ammonium moiety in the 3-position was evaluated. The order of
      antipseudomonal potency of these cephalosporins was as follows: cefaclidine > or
      = FK-518 > cefluprenam = cefozopran > or = ceftazidime > or = cefepime >
      cefpirome > or = cefoselis. Pseudomonas aeruginosa strains derepressed for the
      chromosomally mediated beta-lactamase (cephalosporinase) production were
      relatively susceptible to cefaclidine and FK-518, but were resistant to six other
      cephalosporins. P. aeruginosa strains producing the OXA-1-like penicillinase were
      resistant to cefaclidine, cefepime, and cefpirome, whose frequency was still
      lower. The higher antipseudomonal activity of these compounds than that of
      cefotaxime and some differences in activity among these compounds were suggested
      to result from cephalosporinase stability due to their low affinity for enzyme
      coupled with resistance to enzyme hydrolysis, assuming that the outer membrane
      permeation rates of compounds and their affinities for essential penicillin
      binding proteins were almost the same. The aminothiadiazolyl cephalosporins
      showed higher antipseudomonal activity than the corresponding aminothiazolyl
      counterparts. This was also suggested to result from the same hypothesis as
      described above.

PMID- 8738847
TI  - In vitro activity of fourth generation cephalosporins against enterobacteriaceae
      producing extended-spectrum beta-lactamases.
AB  - The in vitro activity of fourth generation cephalosporins against
      Enterobacteriaceae that produce extended-spectrum beta-lactamases (ESBLs) has not
      been extensively studied. From an examination of the data available in the
      published literature and from studies performed in the author's laboratory,
      several trends are apparent. Introduction of any ESBL into Escherichia coli
      significantly reduces activity. The precise impact of an ESBL on activity varies
      greatly with the specific ESBL present. Derivatives of SHV-1 tend to decrease
      activity more than derivatives of TEM-1 or TEM-2 although there is great
      variation within both of the major types of ESBLs. Activity of fourth generation
      cephalosporins against clinical isolates of ESBL-producing Enterobacteriaceae is
      significantly greater than that of ceftazidime. However, cefotaxime shows
      activity similar to that of fourth generation cephalosporins against certain
      strains. The value of fourth generation cephalosporins in treating infections due
      to ESBL-producing Enterobacteriaceae is currently unknown as there are no
      clinical data available that address this issue.

PMID- 8738848
TI  - Tissue penetration of the fourth generation parenteral cephalosporins.
AB  - In this review, the methods employed to study tissue penetration are discussed.
      Mathematical, animal and human models all have their positive and negative
      features, however studies in man must be central to studying the pharmacokinetics
      of these agents. The newly introduced parenteral cephalosporins (cefpirome,
      cefepime and cefoselis) have been studied in man. In general they penetrate
      tissues to similar extents to other beta-lactam agents. Non-specialised tissues
      such as inflammatory exudate and peritoneal fluid are rapidly and extensively
      penetrated. More specialised tissues (such as prostate) are penetrated to a
      moderate extent (30 to 50%). Certain sites - such as the CSF - are poorly
      penetrated (c. 5 to 10%). It is important to have a knowledge of this information
      prior to therapeutic trials of such agents.

PMID- 8738849
TI  - The penetration of novel intravenous cephalosporins into the lung.
AB  - Relating the concentrations of active antimicrobial at the potential site of
      infection to MIC, may give some indication of clinical efficacy. Where relatively
      insusceptible pathogens are involved, site concentrations are likely to be
      important predictors of efficacy. Unfortunately, there are sources of errors in
      measurement which make the values obtained imprecise. Despite this, broad trends
      are beginning to emerge, especially with bronchial biopsy concentrations. In
      bronchial biopsies, cephalosporins reach approximately 35 to 55% of simultaneous
      serum concentrations, in whole lung tissue 15 to 50% and in ELF 15 to 35%. The
      observed site to serum ratios are consistent with the permeability
      characteristics of cephalosporins and the barriers to movement of drugs into
      sites of infection. There is evidence that inflammation may alter the barriers to
      infection and for the cephalosporins site penetration may be higher. Further work
      is necessary to establish a clear relationship between site concentrations in the
      lung and clinical efficacy.

PMID- 8738850
TI  - Diffusion of 3-quaternary ammonium cephem antibiotics into cerebrospinal fluid of
      patients with bacterial meningitis.
AB  - Cefepime and cefpirome are new beta-lactamase resistant parenteral cephalosporin
      derivatives whose spectrum of activity makes them suitable for use in the
      treatment of severe infections such as bacterial meningitis. However, the
      published information on the penetration of these new agents into human CSF and
      on their use in the treatment of bacterial meningitis are really scarce.
      Experimental studies have shown that cefepime and cefpirome penetrated remarkably
      well into the CSF of animals infected with Streptococcus pneumoniae,
      Streptococcus agalactiae, Staphylococcus aureus, Escherichia coli, Klebsiella
      pneumoniae, Haemophilus influenzae type b or Pseudomonas aeruginosa. The mean
      changes in bacterial colony count in CSF after cefpirome or cefepime
      administration express the antibacterial activity of these drugs. Studies in
      patients show that cefepime and cefpirome crossed the blood-brain barrier and
      reached concentrations in the CSF that are bactericidal against most potential
      pathogens. Higher levels are likely to be achieved with multiple dosing and in
      the presence of inflamed meninges. No study has been performed to investigate the
      efficacy of cefpirome in the treatment of bacterial meningitis. Cefepime was as
      effective and safe as cefotaxime for treatment of patients with bacterial
      meningitis as shown in the only clinical trial.

PMID- 8738851
TI  - Clinical experience with the fourth generation cephalosporins.
AB  - The author reviews the comparative and non-comparative studies of cefepime and
      cefpirome, from which it is evident that both cephalosporins are extremely
      effective both clinically and bacteriologically. Success rates of about 90% have
      been reported for both drugs as therapy for complicated urinary tract infections,
      lower respiratory tract infections of the community as well as of nosocomial
      origin, including a large number of penicillin-resistant Streptococcus pneumoniae
      infections, skin and soft-tissue infections, surgical infections, as well as
      therapy for infections in neutropenic hosts. Cure rates are similar to or better
      than those obtained with ceftazidime, cefotaxime and ceftriaxone. The author also
      points out the various precautions necessary in utilizing these two antimicrobial
      agents.

PMID- 8738852
TI  - The position of recently developed broad-spectrum cephem antibiotics in bacterial
      septicemia.
AB  - In-vitro studies with cefpirome or cefepime prove that both agents are highly
      active against Gram-negative bacilli and Gram-positive cocci. They possess a
      broader spectrum of activity than ceftazidime. In clinical trials cefpirome at
      doses ranging from 1 g to 2 g b.i.d. was compared to ceftazidime at a dose
      ranging from 1 g to 2 g b.i.d. or 2 g t.i.d. Cefepime at a dose of 2 g b.i.d. was
      compared to ceftazidime at a dose of 2 g t.i.d. Both cefpirome and cefepime were
      found to be as effective as ceftazidime in patients with septicemia. These new
      compounds are a valuable addition to the range of drugs available for empiric
      treatment of serious bacterial infections.

PMID- 8738853
TI  - Conclusions: the best cephem molecular structure.

PMID- 8738854
TI  - Pharmacokinetics of pantoprazole in man.
AB  - The proton pump inhibitor pantoprazole is a substituted benzimidazole sulphoxide
      for the treatment of acid-related gastrointestinal diseases such as reflux
      esophagitis, duodenal and gastric ulcers. Pantoprazole, administered as a 40 mg
      enteric coated tablet, is quantitatively absorbed. Its absolute bioavailability
      is 77% and does not change upon multiple dosing. Following a single oral dose of
      40 mg, Cmax is approximately 2.5 mg/l, with a tmax of 2-3 h. The AUC(O,inf.) is
      approximately 5 mgxh/l. Pantoprazole shows linear pharmacokinetics after both
      i.v. and oral administration. Pantoprazole is extensively metabolized in the
      liver, has a total serum clearance of 0.1 l/h/kg, a serum elimination halflife of
      about 1.1 h, and an apparent volume of distribution of 0.15 l/kg. 98% of
      pantoprazole is bound to serum proteins. Elimination half-life, clearance and
      volume of distribution are independent of the dose. The main serum metabolite is
      formed by demethylation at the 4-position of the pyridine ring, followed by
      conjugation with sulphate. Almost 80% of an oral or intravenous dose is excreted
      as metabolites in urine; the remainder is found in feces and originates from
      biliary secretion. The pharmacokinetics of pantoprazole are unaltered in patients
      with renal failure. In patients with severe liver cirrhosis, the decreased rate
      of metabolism results in a half-life of 7-9 h. The clearance of pantoprazole is
      only slightly affected by age, its half-life being approximately 1.25 h in the
      elderly. Concomitant intake of food had no influence on the bioavailability of
      pantoprazole. Pantoprazole showed lack of cytochrome P450 interaction with
      concomitantly administered drugs in any of the studies conducted to date. Lack of
      interaction was also demonstrated with a coadministered antacid. The absence of
      inductive effects on metabolism after chronic administration was first shown by
      using antipyrine as a probe for mixed functional oxidative cytochrome P450
      enzymes. Absence of CYP1A2 induction was confirmed using the specific probe
      caffeine. As sensitive probes for CYP3A enzyme induction, urinary excretion of D
      glucaric acid and 6 beta-hydroxycortisol were also unchanged.

PMID- 8738855
TI  - Multicenter studies on the pharmacokinetic profile of sustained-release oral
      diltiazem (300 mg) after once a day repeated administration: influence of age.
AB  - The influence of age on the pharmacokinetics of the oral sustained release
      diltiazem Mono-Tildiem LP 300 mg was investigated in 12 middle-aged (40-64
      years), 12 elderly (65-80 years) patients and compared to a control group of 54
      young healthy volunteers (18-36 years). Each subject received daily a single dose
      of diltiazem slow release (300 mg) in the morning for 5 consecutive days. On the
      fifth day of treatment, the pharmacokinetic parameters of diltiazem and of 2 of
      its circulating metabolites (N-monodemethyldiltiazem and deacetyldiltiazem) were
      evaluated. The mean diltiazem Cmax was 199.3 +/- 117.8 ng/ml, 254.8 +/- 85.2
      ng/ml and 154.5 +/- 63.2 ng/ml in middle-aged, elderly, and young healthy
      subjects, respectively. Mean plasma Cmin concentration was also higher in elderly
      subjects than in middle-aged and young subjects: 129.7 +/- 77.9 ng/ml versus 66.8
      +/- 56.8 and 66.3 +/- 32.3 ng/ml, respectively. The AUC0-24 showed the same
      trend: 4,042 +/- 1,136 ng/ml.h in elderly, 2,995 +/- 1,905 ng/ml.h in middle
      aged, and 2,564 +/- 1,205 ng/ml.h in young subjects. These parameters were
      statistically higher (p < 0.01) in the elderly subjects than those obtained in
      younger people. No statistical difference was observed between young volunteers
      and middle-aged patients. The Tmax did not differ significantly with age (5.1 +/-
      4.4, 6.8 +/- 2.8, 6.1 +/- 3.5 hours, respectively). The ratios between the AUC of
      each metabolite and that of the parent compound did not vary with the age. These
      results suggest that in elderly people (> 65 y) the bioavailability of diltiazem
      is increased, probably due to a reduction of the first-pass effect. Based on the
      pharmacokinetic results, although safety data did not show any specific trend
      with age, a precautionary reduction of the dose at the start of the treatment
      seems advisable.

PMID- 8738856
TI  - Multiple dose bioequivalence study with josamycin propionate, a drug with highly
      variable kinetics, in healthy volunteers.
AB  - Josamycin is a macrolide antibiotic with considerable intra- and interindividual
      variability in kinetics. In the present study bioequivalence of an intact and
      dispersed josamycin Solutab tablet, containing 1,000 mg of josamycin in the form
      of josamycin propionate ester, was tested versus a Josacine 1,000 mg reference
      sachet. The design of this bioequivalence study was adapted to the drug's
      pharmacokinetic variability, comprising testing in steady-state, testing the
      reference in replicate, and maintaining a widened bioequivalence margin. The
      study was performed in a group of 24 male and 12 female healthy subjects,
      according to a 3-treatment 4-period crossover design. Blood sampling for
      establishing josamycin propionate and josamycin base serum level profiles were
      collected during the 12 h dosing interval on day 4. Steady-state serum levels
      were reached on day 4. With the reference sachet mean peak levels of 1.02
      micrograms/ml and 0.36 microgram/ml were observed for parent drug and metabolite,
      respectively, reached at peak times of 1.5 h and 1.8 h. Comparable profiles were
      observed with the intact and dispersed Solutab tablets, both tending towards
      higher serum levels than the sachet. In terms of josamycin propionate levels as
      well as josamycin base levels, the intact and dispersed Solutab tablet was
      bioequivalent with the referent sachet within the preset 0.70-1.43 margins.
      Variability in josamycin kinetics proved to be substantial, maximum differences
      in peak levels and AUC values being about 10-fold between individuals, and 3-fold
      within individuals. Retrospectively, the multiple dosing regimen appeared not to
      result in a clear reduction of intrasubject variability.

PMID- 8738857
TI  - Effect of cholestyramine resin on single dose valproate pharmacokinetics.
AB  - Cholestyramine, a nonabsorbable anion exchange resin, has been reported to bind
      concomitantly administered drugs and decrease their bioavailability. The
      objective of the study was to determine the effect of cholestyramine on the
      plasma concentrations of valproic acid (VPA) following concurrent and staggered
      (VPA 3 hours before cholestyramine) dosing. Six healthy volunteers participated
      in an open-label, 3-way crossover study. In each phase fasting subjects received
      250 mg of VPA followed by serial blood sampling for VPA plasma concentrations
      over a 37-hour period. In the concurrent and staggered phase the subjects
      received 4 g of cholestyramine (CHOL) twice daily 24 hours prior to and following
      the VPA dose. During the concurrent phase the coadministration of CHOL resulted
      in a decrease (p < 0.05) in the area under the curve (AUC) for VPA compared to
      VPA alone (415.2 +/- 113.2 mg*hr/l vs 489.2 +/- 153.0 mg*hr/l, respectively).
      When the same dose of each drug was administered 3 hours apart, the AUC for VPA
      (454.8 +/- 123.1 mg*hr/l) was not significantly decreased when compared to VPA
      alone (489.2 +/- 153.0 mg*hr/l). Also, the bioavailability relative to VPA alone
      was 86.2% +/- 7.1 for the concurrent phase and 95.3% +/- 13.6 for the staggered
      phase. Based on the AUC of VPA concurrent administration of CHOL significantly
      decreases VPA absorption and separating the doses of the 2 drugs by 3 hours may
      lessen the interaction.

PMID- 8738858
TI  - Activation of protein tyrosine kinase: a possible requirement for fixed-bacteria
      and lipopolysaccharide-induced increase in human natural killer cell activity.
AB  - Preincubation of peripheral blood lymphocytes (PBL) from drug-free, healthy
      volunteers with either the protein tyrosine kinase inhibitor genistein (GNT, n =
      10, final concentration 200 microM) or the protein kinase A activator dybutiryl
      cyclic-AMP (cAMP, n = 11, final concentration 10 microM), resulted in a
      significant inhibition of natural killer cell activity (NKCA, expressed as
      percentage of specific chromium release). With the exception of 4 out of the 11
      cAMP-treated samples, individual values for NKCA in the drug preincubated
      specimens were at least 20% below the same subject baseline activity;
      furthermore, NKC lytic function was non-detectable in 4 out of the 10 and in 1
      out of the 11 samples pretreated with either GNT or cAMP, respectively. PBL
      preincubation with glutaraldehyde-fixed Gram-negative bacteria (GNB, n = 13,
      final GNB-to-effector cell ratio of 50 : 1) resulted in a statistically
      significant increase in NKCA (baseline (x +/- SD) of 21.6 +/- 16.4 and bacteria
      treated samples of 41.5 +/- 24.6, respectively, Student's paired t-test p <
      0.05). At least a 20% increase in NKC lytic function over its own baseline value
      was recorded for 11 out of the 13 samples tested (Table 1). Preincubation with
      GNB and GNT (5 samples) not only blocked the immunostimulant effects of GNB
      (Student's paired t-test p < 0.05), but in most cases individual values for NKCA
      were similar to those recorded for GNT-only treated samples. Use of cAMP instead
      of GNT also blocked, but to a smaller extent, the GNB-produced increases in NKC
      lytic function (paired Student's t-test < 0.05). PBL preincubation with
      lipopolysaccharide (LPS, n = 11, final concentration 50 micrograms/ml) resulted
      in a statistically significant increase in NKCA (baseline (x +/- SD) of 20.7 +/-
      14.1 and LPS treated samples of 39.2 +/- 18.5, respectively, Student's paired t
      test < 0.05). At least a 20% increase in NKCA over its own baseline value was
      observed for each and everyone of the 11 samples studied (Table 2). Addition of
      LPS and GNT to the incubation mixture resulted not only in inhibition of the NKCA
      upmodulating LPS effects (Student's paired t-test p < 0.05), but each and
      everyone of the individual samples' NKCA were, in fact, significantly lower than
      their corresponding control baseline values and similar to those recorded for GNT
      only treated samples. However, the use of LPS and cAMP (Table 2) produced less
      dramatic results, significant inhibition of LPS effect were recorded in only 2
      samples (Nos 8 and 10), and individual NKCA in the remaining 3 specimens was
      significantly higher than the corresponding baseline value. Whereas experimental
      results obtained with GNT support the involvement of PTK-dependent pathways in
      the stimulation of human NKCA produced by GNB and LPS, cAMP experiments suggest
      modulation of PKA-dependent pathways as responsible for the decrease in NK lytic
      function produced by a number of chemicals involved in the pathophysiology
      associated with certain forms of stress, including septic shock. Further research
      in this area could help in the rational design of pharmacological approaches for
      the treatment of these conditions.

PMID- 8738859
TI  - Effect of treatment with magnesium and potassium on mortality and reinfarction
      rate of patients with suspected acute myocardial infarction.
AB  - The aim of the study was to test whether magnesium and potassium administration
      can decrease both early and late cardiac event rates in 355 patients with
      suspected acute myocardial infarction (AMI). The study was conducted by a primary
      and secondary care research centre as a randomized, initially double-blind
      comparison for 4 weeks followed by a single blind period for 2 years. Patients
      with definite or possible AMI and unstable angina based on World Health
      Organization criteria were assigned within 24 hours of infarction to different
      groups. Treatment was administered for 3 days through intravenous infusion with
      either 8.12 mmol/day Mg (group A, n = 81), 10.49 mmol/day K (group B, n = 77) 10%
      dextrose solution (group C, n = 87) or a placebo containing 2% dextrose solution
      (group D, n = 81). After discharge from the hospital all groups were advised to
      follow a fat-reduced diet. Groups A, B, and C were also advised to take magnesium
      hydroxide or potassium chloride orally. Comparison of groups A and B with group D
      over 2 years indicated that treatment with magnesium or potassium was associated
      with increased (p < 0.05) serum magnesium and potassium, and significant
      reduction in the incidence of cardiac events (22 and 24 vs 41 patients), total
      mortality (9 and 10 vs 20 deaths), and ventricular ectopics (17 and 21 vs 44),
      respectively, in the groups. Group C showed no significant benefit. It is
      possible that magnesium and potassium infusion immediately after AMI and addition
      of Mg and K salts to the AMI regimen may enhance tissue levels of these cations,
      leading to significant reduction in complications and mortality after 2 years.

PMID- 8738860
TI  - Establishment of a reliable extraction method of estrone sulfate from bovine
      plasma for detection of the peripheral level during the regular estrous cycle by
      radioimmunoassay.
AB  - A simple extraction and assay technique of estrone sulfate in bovine blood was
      developed with the object of detecting the peripheral level of estrone sulfate in
      a normal estrous cycle or in early pregnancy. Estrone sulfate in bovine plasma
      was extracted with a small reversed phase cartridge. The steroid conjugate
      retained in the cartridge was eluted with 40% (v/v) methanol. Estrone sulfate was
      separately recovered from other steroids by the stepwise increase in methanol
      concentration in the elution solvent. The recoveries of estrone sulfate eluted
      with 40% methanol were more than 90%, irrespective of the applied plasma volume.
      The concentration measured by radioimmunoassay with the eluent of 40% methanol
      was consistent for plasma extraction volumes of 0.5-2.0 ml. The change of estrone
      sulfate in bovine peripheral plasma during the regular estrous cycle was
      determined with a small reversed phase cartridge for extraction and 40% methanol
      for elution. The change in estrone sulfate was found to be similar to the change
      of estrone and estradiol-17 beta. The concentration of estrone sulfate was not
      higher than that of both estrogens in cattle.

PMID- 8738861
TI  - The ontogeny of serum insulin-like growth factor-I concentration in foals:
      effects of dam parity, diet, and age at weaning.
AB  - The effects of dam parity, age at weaning, and preweaning diet were examined in
      the ontogeny of serum insulin-like growth factor-I (IGF-I) concentrations in
      foals. Foals born to 13 primiparous and 19 multiparous draft-cross mares were
      weighed and bled near birth. About one-half of the foals in each group were
      weaned early (about 13 wk old); the remaining foals were weaned late (about 16 wk
      of age). Pooled values for serum IGF-I concentrations between birth and 17 wk of
      age were higher (P < 0.065) for foals born to multiparous (386 ng/ml) than to
      primiparous mares (237.5 ng/ml). Colts (378 ng/ml) had higher (P < 0.05) serum
      IGF-I concentrations than fillies (254.5 ng/ml), regardless of dam parity. Colts
      (173.5 kg) also tended (P = 0.12) to be heavier than fillies (159.2 kg). Weaning,
      whether at 13 or 16 wk of age, reduced (P < 0.05) growth rates and serum IGF-I
      concentrations. Serum IGF-I values recovered to preweaning values within 1-3 wk
      postweaning concurrent to an improved weight gain. Fifteen 1-d-old foals in a
      second study were fed milk replacer for 7 wk and were compared with five foals
      that nursed their mares for 8 wk. During the first 2 wk, replacer-fed foals (0.46
      kg/d) did not gain as rapidly (P < 0.03) as mare-nursed foals (1.73 kg/d). The
      associated serum IGF-I values for replacer foals (139.4 ng/ml) were lower (P <
      0.0001) than values for mare-nursed foals (317.4 ng/ml). Despite similarity in
      gains for both groups there-after, serum IGF-I concentrations of replacer-fed
      foals were only 36 and 60% of values obtained for mare-nursed foals at 8
      (weaning) and 18 wk of age, respectively. The intrinsic differences between mare
      nursed and milk-replacer foals in serum IGF-I concentrations persisted to 1 yr of
      age despite similarities in dietary management and body weight of the foals. At 1
      yr of age, the serum IGF-I concentration of mare-nursed foals (1,203 ng/ml) was
      48% higher than that of replacer-fed foals (815 ng/ml). These data indicate that
      dam parity, sex of foal, and preweaning nutrition affect the ontogeny of serum
      IGF-I concentration in the foal. The chronic, persistent difference in serum IGF
      I values created by the early nutritional management of growing animals has
      implications in the interpretation of longitudinal serum IGF-I studies in all
      species.

PMID- 8738863
TI  - Hormonal and nutritional modulation of hepatic arginase activity in growing
      cattle.
AB  - The hormonal and nutritional modulation of hepatic arginase activity (HARG) was
      characterized in growing cattle in two studies. In the first study, 20 steers
      (initial weight, 182 +/- 2 kg) were assigned in equal numbers to either Synovex-S
      (SYN) (ear implant), recombinant bovine somatotropin (Somavubove; SbV; 0.1 mg/kg
      intramuscularly daily), SYN + SbV, or nothing (control). Steers were individually
      fed, for 56 d, a concentrate (80% diet dry matter [DM]) and silage (20% diet DM)
      diet providing 20 g of crude protein (CP) and 252 kcal metabolizable energy (ME)
      per kg body weight0.75. On Day 57, samples of liver were obtained at slaughter
      and subsequently assayed for HARG by the incubation of a tissue homogenate for 2
      hr with 250 mM arginine, with and without Mn2+ and heat activation, and the
      measurement of the resulting urea. HARG was uniformly increased by divalent
      cation (Mn2+) and heating. SYN had no effect on HARG, whereas SbV treatment
      resulted in an overall 34% decrease in HARG. Plasma urea nitrogen (PUN) was
      decreased by SbV but not consistently affected by SYN. In the second study, 16
      steers (avg. initial weight, 284 +/- 5 kg) were initially fed a concentrate basal
      diet consisting of 11% CP and 1.96 Mcal ME for 21 d. Steers were then assigned to
      one of four dietary treatments (6.4 kg DM/hr per day) in a factorial arrangement
      of high and low CP (8 and 14%) and two levels of energy (1.96 and 2.67 Mcal ME/kg
      of diet DM) for 210 d and slaughtered. HARG and PUN were higher in steers fed 14%
      CP but were lower at each level of CP fed at the higher level of ME. The data
      suggest that hormonal repartitioning compounds and diet composition may modulate
      nitrogen metabolism by affecting the activity of arginase in the liver as well as
      by affecting the total content of arginase in association with changes in organ
      size.

PMID- 8738862
TI  - Effects of administration of N-methyl-D,L-aspartate (NMA) on gonadotropin
      secretion in untreated and steroid-treated ovariectomized mares during the
      breeding season and in intact and ovariectomized mares during anestrus.
AB  - The purpose of this experiment was to investigate whether N-methyl-D,L-aspartate
      stimulated gonadotropin secretion in mares and to determine the response in two
      experimental paradigms where gonadotropin secretion is low or elevated. In
      Experiment 1, conducted during the breeding season (summer), eight long-term
      ovariectomized mares were treated daily for 21 d with progesterone plus estradiol
      (n = 4) or oil vehicle. Beginning on Day 14, each mare received, in a randomized
      design on alternate days, an intravenous injection of either 0, 0.5, 1.0, or 5.0
      mg/kg NMA. Treatment with NMA was not accompanied by a change in gonadotropin
      release in vehicle-treated ovariectomized mares. In steroid-treated mares,
      gonadotropin values were suppressed compared with vehicle controls, but NMA only
      induced a significant increase in follicle-stimulating hormone (FSH) and only at
      the highest dose. In Experiment 2, the effect of the administration of NMA was
      compared in intact anestrous mares (n = 4) and long-term ovariectomized mares (n
      = 4) during the nonbreeding season. At the highest doses (1.0 and 5.0 mg/kg), NMA
      induced a significant increase in luteinizing hormone (LH) and FSH in intact
      mares. In contrast, pretreatment concentrations of LH and FSH were higher in long
      term ovariectomized mares and NMA only increased LH, but not FSH, at the highest
      dose. The results demonstrate that the administration of NMA stimulates the
      release of LH and FSH in mares. During anestrus, ovarian intact mares appear more
      responsive than long-term ovariectomized mares. At high doses, NMA may induce
      differential release of the gonadotropins in long-term ovariectomized mares.

PMID- 8738864
TI  - Interaction of cyclic AMP- and calcium-dependent mechanisms in the regulation of
      growth hormone-releasing hormone-stimulated growth hormone release from ovine
      pituitary cells.
AB  - Growth hormone-releasing hormone (GHRH)-stimulated growth hormone (GH) release
      from the sheep pituitary is mediated through Ca(2+)-and cyclic AMP-dependent
      mechanisms. The initial Ca2+ influx is suggested to result from depolarization,
      whereas a secondary Ca2+ influx is thought to result from second messengers. This
      study sought to determine whether there was an interaction between these two
      signal transduction pathways. Sheep pituitary cells were placed in culture for 4
      d and were then washed and incubated for 1 hr in serum-free medium before the
      application of specific antagonises and/or agonists. Both KCl and forskolin
      stimulated GH release (P < 0.05), but neither produced an effect similar to that
      of GHRH. The combination of both stimuli, however, mimicked GH release, as seen
      with a maximal dose of GHRH. Pretreatment with H89 (protein kinase A [PKA]
      inhibitor) inhibited GHRH, forskolin- and KCl-stimulated GH release (P < 0.001)
      but had no effect on phorbol myristate acetate (PMA)-stimulated GH release.
      Verapamil (voltage-dependent Ca2+ channel blocker) inhibited the GHRH effects on
      GH release (P < 0.0002) but did not influence forskolin or PMA actions. These
      data suggest that Ca(2+)-dependent pathways converge with cyclic AMP-dependent
      pathways before or with the activation of PKA. The data also suggest that PKA
      activation by cyclic AMP alone is insufficient to reproduce either the effects of
      GHRH stimulation or the combined effects of Ca2+ influx plus PKA activation on GH
      release. A calmodulin blocker, W7, reduced GHRH-stimulated GH release, a
      reduction equivalent to the Ca2+ effect on GH release. This suggests that Ca2+
      activates calmodulin, which in turn enhances adenylyl cyclase and/or PKA activity
      to release GH from the sheep pituitary.

PMID- 8738865
TI  - Insulin-like growth factors-I and -II, somatotropin, prolactin, and placental
      lactogen are not acute effectors of lipolysis in ruminants.
AB  - The acute regulation of lipolysis in the adipose tissue of ruminants was
      evaluated with lactating cows (n = 4) and growing ewe lambs (n = 11).
      Subcutaneous adipose tissue was obtained by biopsy or at slaughter and was
      incubated with varying concentrations of biologically active insulin-like growth
      factors-I and -II (IGF-I, IGF-II), somatotropin (ST), prolactin (PRL), or
      placental lactogen (PL) to determine the effect of these hormones on lipolysis.
      Complimentary studies were conducted to examine the effects of IGF-I and IGF-II
      on the acute regulation of lipolysis in adipose tissue from lactating ewes and
      wethers under a variety of incubation conditions. Isoproterenol (ISO), a beta
      adrenergic agonist known to rapidly stimulate lipolysis, was used as a positive
      control. Incubation with ISO for 3 hr resulted in a significant increase in the
      rates of lipolysis. However, there was no stimulation of lipolysis over the 3-hr
      incubation at any concentration or under any conditions for IGF-I or IGF-II.
      Furthermore, ST, PRL, or PL had no acute effects on the rates of lipolysis in
      adipose tissue. These data demonstrate that IGF-I, IGF-II, ST, PRL, and PL are
      not acute effectors of the lipolytic rate in the adipose tissue of ruminants.

PMID- 8738866
TI  - Growth hormone-releasing hormone and somatostatin concentrations in the
      hypophysial portal blood of conscious sheep during the infusion of growth hormone
      releasing peptide-6.
AB  - The effects of growth hormone-releasing peptide-6 (GHRP-6) on peripheral plasma
      concentrations of growth hormone (GH) and hypophysial portal plasma
      concentrations of growth hormone-releasing hormone (GHRH) and somatostatin (SRIF)
      were investigated in conscious ewes. Paired blood samples were collected from the
      hypophysial portal vessels and from the jugular vein of nine ewes for at least 2
      hr. The sheep were then given a bolus injection of 10 micrograms of GHRP-6 per kg
      followed by a 2-hr infusion of GHRP-6 (0.1 microgram/kg.hr). Blood sampling
      continued throughout the infusion and for 2 hr afterwards. An increase in plasma
      GH concentration was observed in the jugular samples of six of the nine ewes (1.4
      +/- 0.3 vs 7.4 +/- 2.0 ng/ml, P < 0.05) 5-10 min after the GHRP-6 bolus
      injection, but in no case did we observe a significant coincident release of
      GHRH. During the infusion period, mean plasma GHRH levels were not significantly
      increased but there was a 50% increase (P < 0.05) in GHRH pulse frequency; GHRH
      pulse amplitude was not changed. Mean SRIF concentration, pulse frequency, and
      pulse amplitude were unchanged by GHRP-6 treatment. These data indicate that GHRP
      6 causes a small, but significant effect on the pulsatile secretion of GHRH,
      indicating action at the hypothalamus or higher centers of the brain. The large
      initial GH secretory response to GHRP-6 injection does not appear to be the
      result of GHRP-6 action on GHRH or SRIF secretion.

PMID- 8738867
TI  - Effects of corticotropin-releasing hormone, lysine vasopressin, oxytocin, and
      angiotensin II on adrenocorticotropin secretion from porcine anterior pituitary
      cells.
AB  - The aim of this study was to determine the ability of corticotropin-releasing
      hormone (CRH), lysine vasopressin (LVP), oxytocin (OT), and angiotensin II (AII)
      to stimulate adrenocorticotropin (ACTH) secretion from porcine anterior pituitary
      (AP) cells in vitro and to evaluate the role of protein kinase C (PKC) in the
      interaction between CRH and LVP. In this study, porcine AP cells were
      enzymatically and mechanically dispersed, cultured (150,000 cells/well) for 4 d,
      and then challenged with doses of various neuropeptides for 3 hr. CRH (10(-7)-10(
      10) M) was the most potent of the peptides tested in stimulating ACTH release
      from porcine AP cells. In fact, none of the other peptides consistently affected
      ACTH concentrations relative to basal levels. However, LVP potentiated CRH
      action, even though by itself, it failed to stimulate ACTH production. Neither OT
      or AII potentiated CRH-stimulated ACTH release from porcine AP cells. To
      determine whether the inter-action between CRH and LVP was regulated partially by
      the protein Kinase C (PKC) pathway, we challenged AP cells in a 30-min incubation
      with 10(-7) M staurosporine (ST), a treatment predicted to decrease PKC activity.
      Then, cells were washed and challenged with 10(-9) M LVP, 10(-9) M CRH, and 10(
      9) M CRH + LVP. Treatment with ST decreased (P < 0.05) CRH + LVP-stimulated ACTH
      release. To further demonstrate an interaction between protein kinase A (PKA) and
      PKC transduction pathways in the observed synergism between CRH and LVP to
      enhance ACTH secretion, we also challenged AP cells with 10(-7) M phorbol 12, 13
      myristate acetate (PMA) and 5 microM forskolin (FOR) for 3 hr. This treatment was
      predicted to enhance PKA and PKC activities, respectively, and thereby enhance
      ACTH concentrations. Challenging cells with FOR + PMA enhanced (P < 0.001) ACTH
      release above basal concentrations, but more important, it increased (P < 0.001)
      ACTH concentration above that elicited by either drug given alone. Taken
      together, our in vitro studies support the conclusion that CRH is the principal
      regulator of ACTH secretion in the pig. In contrast to the results in most other
      species evaluated, vasopressin alone did not affect ACTH release. However, LVP
      can enhance the effectiveness of CRH in releasing ACTH, and this enhancement
      appears to rely, at least in part, on the activation of the PKC signal
      transduction pathway.

PMID- 8738868
TI  - Calcitonin mRNA expression and plasma calciotropic hormones in fetal lambs.
AB  - The object of this study was to measure basal levels of calciotropic hormones
      during gestation in the ovine fetus. Thyroid glands and plasma samples were
      collected from 49 Ile de France x (Limousine x Romanov) fetuses (range, 80 to 145
      d). Total thyroidal RNA was extracted for calcitonin (CT) mRNA analysis. Plasma
      immunoreactive concentrations of CT, parathyroid hormone (PTH), parathyroid
      hormone-related peptide (PTHrP), and 1,25-dihydroxy-vitamin D [1,25-(OH)2D] were
      assayed. Plasma Ca and P concentrations were measured by atomic absorption
      spectrophotometry and colorimetry, respectively. The ratio of thyroidal
      weight/body weight decreased twice between Days 80 and 145 of gestation.
      Simultaneously, the CT mRNA rate increased but did not significantly vary after
      89 d of gestation. Plasma CT concentration increased between 80 and 89 d and then
      did not significantly vary until Day 145. We could not detect PTH in ovine
      fetuses plasma; PTHrP concentration did not vary significantly between Days 80
      and 145. The concentration of 1,25-(OH)2D decreased in plasma essentially between
      Days 110 and 145. In conclusion, between Days 80 and 145 of gestation, CT, PTHrP,
      and 1,25-(OH)2D concentrations can be easily measured in plasma from ovine
      fetuses, but plasma PTH was undetectable. In basal conditions, no relationship
      could be demonstrated between any hormonal concentrations in the fetal plasma and
      that of Ca or P.

PMID- 8738869
TI  - Pulsatile secretion of prolactin in laying and incubating turkey hens.
AB  - Incubation behavior in the turkey hen is associated with a large increase in
      prolactin secretion. Previous research using hourly sampling of incubating hens
      has shown that prolactin levels fluctuate widely throughout a 24-hr period,
      suggestive of pulsatile secretion. This study compared the prolactin secretory
      patterns of laying and incubating turkeys to determine if prolactin is secreted
      episodically and if the high prolactin levels characteristic of the incubating
      hen may result, at least in part, from a change in the amplitude or frequency of
      secretory pulses. Blood samples were collected from cannulated, unrestrained
      laying and incubating hens at 10-min intervals for up to 24 hr. Data were
      analyzed with the PULSAR program to determine baseline prolactin levels and to
      establish the magnitude, frequency, and duration of episodic secretory peaks. The
      results revealed tha prolactin is secreted in a pulsatile pattern in both laying
      and incubating turkey hens. Incubating hens had ninefold higher mean and baseline
      plasma prolactin levels than laying hens. The prolactin pulses were of
      approximately 12-fold greater amplitude in incubating hens than in laying hens,
      but the duration and frequency of pulses were the same in both groups. Therefore,
      the high prolactin levels required for incubation do not appear to result from an
      increase in the frequency of lactotroph stimulation, but rather from an increase
      in the prolactin secretion rate.

PMID- 8738870
TI  - Nutrition and immunity with emphasis on infection and autoimmune disease.
AB  - Nutrition and nutritional status can have profound effects on immune functions,
      resistance to infection and autoimmunity in man and other animals. Nutrients
      enhance or depress immune function depending on the nutrient and level of its
      intake. Protein-energy malnutrition and vitamin A deficiency are strongly
      associated with impaired immunity and infectious disease. The essential role
      vitamin A plays in infection and maintenance of mucosal surfaces has long been
      known. Recent evidence shows that T-cell subpopulations, cytokines and antibody
      subclasses are all affected by vitamin A. In animal studies supplementation with
      vitamin E protects against infection and is linked to stimulatory effects on the
      immune system. In man vitamin E and other anti-oxidants increase the number of
      CD4+ cells. Dietary lipids and zinc have a substantial impact on autoimmunity
      from protective to potentiation of immuno-pathological processes in animals.
      There is considerable potential to modify human autoimmune disease by
      manipulation of lipid nutrition. Deficiency of pyridoxine induces atrophy of
      lymphoid organs, marked reduction in lymphocyte numbers, impairs antibody
      responses and IL-2 production. Dietary copper is important in the prevention of
      infection in some animal species and T-cell function is defective under
      deficiency states due to an inability to produce IL-2. Selenium has been linked
      to viral infection, enhanced T-cell functions and TNF beta induced increase in
      natural killer cell activity. Understanding the molecular and cellular
      immunological mechanisms involved in nutrient-immune interactions will increase
      our applications for nutrition of the immune system in health and in disease

PMID- 8738871
TI  - The coming of vegetables, fruits and key nutrients to the European diet.
AB  - On the basis of evidence now accumulating, vegetables and fruits were not always
      an integral part of the European diet. Prior to 1800, vegetables and fruits were
      not esteemed but rather looked down upon. It has only been over the past two
      centuries that these two critical foods have come into vogue. First, they had to
      be accepted by a growing number of medical men and observers. Then, once licensed
      as edible foods, vegetables and fruits, starting with the potato, actually did
      make their way into every man's diet. And by the end of the nineteenth century,
      these rich sources of carotene and Vitamins A, C and E became so universal that
      Europeans now forgot that a hundred years earlier these foods had barely been
      consumed.

PMID- 8738872
TI  - Mycotoxicosis--humankind's greatest affliction?

PMID- 8738873
TI  - The validation of a test to measure knowledge about the fat content of food
      products.
AB  - The objective of the study was to develop and validate a 21-item nutrition
      knowledge test to measure people's knowledge of the fat content of food-products.
      After pretesting and provisional development, the test was administered twice to
      study test-retest reliability. Furthermore, various sub-populations with expected
      differences in nutrition knowledge completed the test in order to study the
      construct validity of the questionnaire. The subpopulations consisted of lay
      people (N = 81), students of human nutrition and dietetics (N = 108), and
      professional experts (N = 79) on human nutrition. The internal consistency and
      uni-dimensionality of the test were determined by calculating the KR-20 statistic
      and the log-likelihood ratio statistic for the Rasch model. Pearson's correlation
      and gross misclassification between T1 and T2 were calculated to assess the test
      retest reliability. Analysis of variance was used to test for differences in mean
      knowledge scores between subpopulations. Test-retest reliability was found to be
      sufficient (R = .85). The internal consistency was moderate (KR20 = .68).
      According to the Rasch model, two items had to be removed from the test before
      the log-likelihood ratio statistic of the Rasch model indicated that knowledge
      about the fat content of food products as assessed by the questionnaire is a uni
      dimensional construct. The differences in mean knowledge scores between the
      subpopulations were significant (p < .01) and in the expected direction (experts
      > students > lay people). It can be concluded that the test is a reliable and
      valid instrument to measure knowledge about total fat content in food products
      and that the Rasch model is a comprehensive method to indicate the reliability of
      nutritional knowledge tests.

PMID- 8738874
TI  - Policy considerations for a realistic approach to hunger in Nigeria.
AB  - Hunger is usually caused by a break down in the food security mechanisms of a
      society and lack of purchasing power. In Nigeria, food shortages have become
      common since 1972, culminating in the food crises of the 1980s, made worse by the
      implementation of a macroeconomic economic adjustment policy in 1986. The paper
      confirms the hunger situation and presents evidence to show that it is of wider
      significance than hitherto acknowledged. The paper proposes policy options to
      tackle the situation and these include the development of agriculture to attain
      self-sufficiency in staple food production which must be backed by political will
      using a widely accepted framework and well articulated set of programmes and
      strategies borne out or consensus.

PMID- 8738875
TI  - Caring capacity in the management of the nutrition crisis in infants, young
      children and women in Nigeria.
AB  - Nigeria's nutrition crisis has been shown to have a considerable negative impact
      on infants, young children and women. Available evidence suggests that 'caring
      capacity' when properly planned and targeted at the most-at-risk can help.
      Strategies that can achieve this care are increasing women's income and control
      over income, increasing investment in women's education and improving access to
      credit facilities. Others are the aggressive promotion of gender-biased labour
      saving technology, increasing women's access to basic health and family planning
      services and implementing reforms in land ownership while instituting social
      security for women.

PMID- 8738876
TI  - Evolution of neuropeptide Y, peptide YY and pancreatic polypeptide.
AB  - The neuropeptide Y family of peptides consists of neuropeptide Y (NPY), which is
      expressed in the central and peripheral nervous systems, and peptide YY (PYY) and
      pancreatic polypeptide (PP) which are gut endocrine peptides. All three peptides
      are 36 amino acids long and act on G-protein-coupled receptors. NPY and PYY are
      present in all vertebrates, whereas PP probably arose as a copy of PYY in an
      early tetrapod ancestor. NPY is one of the most conserved peptides during
      evolution and no gnathostome (jawed) species differs from the ancestral
      gnathostome sequence at more than five positions. PYY is more variable,
      particularly in mammals which have nine differences to the gnathostome ancestor.
      PP may be the most rapidly evolving neuroendocrine peptide among tetrapods with
      only 50% identity between mammals, birds, and amphibians. Ancestral gnathostome
      NPY and PYY seem to have differed at only four positions, suggesting that the
      gene duplication occurred shortly before the appearance of the gnathostomes. The
      two peptides differ from one another at 9-12 positions in tetrapod species and
      share at least two receptor subtypes in mammals. In bony and cartilaginous
      fishes, NPY and PYY have only 5-6 differences which, together with more extensive
      neuronal localization of PYY, indicate an even greater functional overlap between
      the two peptides in these animal groups. The emergence of sequence information
      for several receptor subtypes from various species will shed additional light on
      the evolution of the functions of the NPY-family peptides.

PMID- 8738877
TI  - Corticostatins/defensins inhibit in vitro NK activity and cytokine production by
      human peripheral blood mononuclear cells.
AB  - Corticostatins/defensins are a family of cationic peptides recently isolated from
      phagocytotic cells of the myeloid lineage. Natural killer (NK) cells are
      spontaneously cytotoxic large granular lymphocytes that are involved in
      immunosurveillance against cancer and infections. Their activity is modulated by
      hormones of the hypothalamic-pituitary-adrenal axis. We wished to determine
      whether two human corticostatins/defensins, HP-1 and HP-4, are able to change in
      vitro the spontaneous NK activity of human peripheral blood mononuclear cells
      (PBMC) and the responses either to the stimulatory cytokines immune interferon
      (IFN-gamma) or interleukin 2 (IL-2) and to the inhibitory hormone cortisol. NK
      cell activity was measured in a 4-h direct cytotoxicity assay with K562 cells as
      a target. HP-1 and HP-4 (10 (-8) -10 (-9) M) significantly inhibited the
      spontaneous and cytokine-inducible NK activity, and increased the cortisol
      dependent inhibition. Radioimmunoassay of HPLC purified fractions obtained from
      sonicated NK cells showed HP-1 in the two cell preparations examined. We also
      evaluated the effects of HP-1 and HP-4 (10 (-8) M -10(-9) M) upo IFN-gamma and
      interleukin 6 (IL-6) production by PBMC stimulated with phytohemagglutinin (PHA)
      or concanavalin A (ConA). IFN-gamma was titrated with the biological assay using
      WISH cells as indicators and vescicular stomatitis virus (VSV) as the challenge
      virus. IL-6 was measured using an enzyme amplified sensitivity immunoassay. Both
      HP-1 and HP-4 significantly reduced cytokine production. Our data indicate that
      corticostatins/defensins are novel modulators of lymphocyte functions in vitro.
      Their immunodepressing properties could add complexity and plasticity to
      hypothalamic-pituitary-adrenal-cytokine circuits in vivo.

PMID- 8738878
TI  - GLP-1 depolarizes the rat pancreatic beta cell in a Na(+)-dependent manner.
AB  - An intestinal hormone glucagon-like-peptide-1 (GLP-1) is a prominent candidate
      for incretin. In vitro experiment showed (Fridolf and Ahren, Mol. Cell.
      Endocrinol., 96 (1993) 85-90) that GLP-1 increased both insulin secretion and the
      efflux of 45Ca2+ in a Na(+)-dependent manner. Further, GLP-1 depolarizes the
      pancreatic beta cells in the presence of high concentration of glucose. Here, we
      report the effect of GLP-1 on the membrane potential with a physiological
      concentration of glucose in perforated patch clamp of primary cultured rat beta
      cells. 10 nM GLP-1 depolarized the beta cell, which was completely reversed by
      replacing Na+ with the impermeant molecule N-methyl-D-glucamine (NMDG). The Ca2+
      channel blocker, Co2+ suppressed the Ca2+ spikes without hyperpolarizing the
      cell. GLP-1-induced insulin secretion in perifused islets was also suppressed by
      a prior replacement of Na+ with NMDG. In addition, GLP-1 slightly augmented the
      long-lasting Ba2+ current, which was reverted to the control level by a selective
      inhibitor of protein kinase A, H-89. These results indicate: (i) GLP-1
      depolarizes the beta cell by activating the membrane Na+ permeability; (ii) GLP-1
      slightly modulates the L-type Ca2+ channel probably through protein kinase A; and
      (iii) at least in part, these mechanisms may be involved in the insulin secretion
      induced by GLP-1.

PMID- 8738880
TI  - Vascular effects of oxytocin on human middle cerebral artery determined by
      transcranial Doppler sonography.
AB  - Neurohypophysial hormones may exert regulatory influences on cerebral blood flow.
      This double-blind cross-over study in healthy humans (n = 6) examined effects of
      oxytocin (OX) on blood flow in the middle cerebral artery (MCA) by transcranial
      Doppler sonography. Compared to placebo, intravenous infusion of OX (0.5 IU,
      within 2.5 min via a forearm catheter) reduced blood flow velocity (V) within 10
      min after the start of the infusion (P < 0.05). The pulsatility index (PI) was at
      the same time increased following OX (P < 0.05). The effects of OX were not
      accompanied by changes in expiratory endtidal pCO2 or blood pressure. But, heart
      rate was slightly enhanced immediately after infusion of OX (P < 0.05). The
      changes in MCA blood flow velocity following OX could reflect a vasoconstrictory
      effect on small cerebral resistance vessels or a vasodilating effect on the large
      cerebral arteries.

PMID- 8738879
TI  - Proglucagon processing in islet and intestinal cell lines.
AB  - To investigate the factors involved in the post-translational processing of
      proglucagon, we have examined the proglucagon-derived peptides (PGDPs) expressed
      in normal mouse pancreas and intestine, as well as in both islet (InR1-G9, RIN
      1056A) and intestinal (STC-1) cell lines. N-terminal proglucagon processing was
      similar to that of normal mouse pancreas in InR1-G9 cells, but differed in RIN
      1056A and STC-1 cells, which contained significant amounts of glucagon as well as
      the intestinal PGDPs, glicentin and oxyntomodulin. The C-terminal end of
      proglucagon was processed to small amounts of glucagon-like peptide-1 in InR1-G9
      and RIN 1056A cells, as in normal pancreas, while processing was more extensive
      in both STC-1 cells and normal intestine. Northern blot analysis of mRNA
      transcripts for the prohormone convertases, PC1 and PC2, in the 3 cell lines
      demonstrated correlations between PC2 and the presence of glucagon, as well as
      between PC1 and production of the intestinal PGDPs. These findings provide
      support for the suggestion that PC1 and PC2 play roles in the tissue-specific
      post-translational processing of proglucagon.

PMID- 8738881
TI  - Peptidase inhibitors potentiate lysylbradykinin-induced bronchoconstriction in
      the rat.
AB  - To determine whether lysylbradykinin (LBK, kallidin) causes bronchoconstriction
      in animals and if peptidase inhibitors modulate the response, we studied the
      effects of LBK administered by aerosol in rats and assessed whether pretreatment
      with aerosolized solutions of enalaprilat, an inhibitor of angiotensin converting
      enzyme (ACE), or phosphoramidon, an inhibitor of endopeptidase 24.11 (EP 24.11,
      neutral endopeptidase), altered the response. Accordingly, LBK-induced
      bronchoconstriction was measured in anesthetized, mechanically ventilated,
      specific pathogen-free, Sprague-Dawley rats by body plethysmography and followed
      by continuous determination of lung resistance (RL) and maximal expiratory flow
      (MEF). Incremental doses of aerosolized LBK were administered by nebulization to
      obtain a concentration that caused a 5-15% increase in RL, which was designated
      the BC10 dose. We found that pretreatment with aerosolized enalaprilat (1 mM) 3
      min prior to a BC10 dose of LBK significantly increased RL as compared to the
      BC10 dose alone (129 +/- 4.1% vs. 105 +/- 2.4%, P < 0.002, n = 4) and
      significantly decreased MEF (83 +/- 1.5% vs. 97 +/- 1.4%, P < 0.008, n = 4).
      Following pretreatment with aerosolized phosphoramidon (1 mM), significant
      increases in RL (113 +/- 1.4% vs. 106 +/- 1.6%, P < 0.019, n = 7) and decreases
      in MEF (92 +/- 0.9% vs. 95 +/- 0.9%, P < 0.035, n = 7) were observed (paired
      Student's t-test). The above findings demonstrate the effects of LBK on airway
      caliber for the first time in an animal model, and suggest that ACE and EP 24.11
      contribute to degradation of the peptide in the airway.

PMID- 8738882
TI  - A galanin-mastoparan chimeric peptide activates the Na+,K(+)-ATPase and reverses
      its inhibition by ouabain.
AB  - The effect of the neuropeptide galanin, the wasp venom toxin amphiphilic peptide
      toxin mastoparan and the chimeric peptide, galparan, consisting of N-terminal 13
      amino acids of neuropeptide galanin linked at C-terminus to mastoparan amide (and
      its inactive analog Mas17) on the activity of Na+,K(+)-ATPase has been studied.
      Mastoparan inhibits the activity of the Na+,K(+)-ATPase with IC50 = 7.5 microM
      and also reduces the cooperativity for Na+ and K+, respectively, while galanin
      has no effect on the Na+,K(+)-ATPase activity. The chimeric peptide, galanin(1
      13)-mastoparan amide (galparan), exhibits biphasic interaction with Na+,K(+)
      ATPase, it activates the enzyme at maximal stimulating concentration of 4 microM
      followed by inhibition of the enzyme with IC50 of 100 microM. At maximum
      stimulating concentration (4 microM), galparan partly reduces the cooperativity
      only for Na+ and it also counteracts the inhibitory effect of oubain on Na+,K(+)
      ATPase. Galparan's stimulatory effect was influenced by ATP. The chimeric peptide
      [19Lys,26Leu]-galparan, containing the inactive analog of mastoparan (Mas17), has
      no effects on rat brain Na+,K(+)-ATPase activity. Both chimeric peptides galparan
      and [19Lys,26Leu]-galparan are high-affinity galanin receptor ligands with IC50
      of 6.4 nM and 0.71 nM, respectively, while galanin (1-13) and mastoparan alone
      have significantly lower affinity for the galanin receptor, IC50 of 125 nM and 1
      microM, respectively. The ability of chimeric peptides to bind to galanin
      receptors does not correlate with their effects on the Na+,K(+)-ATPase.

PMID- 8738883
TI  - Natriuretic peptide system in the rat submaxillary gland.
AB  - Natriuretic peptides and their receptors were characterized in rat submaxillary
      glands (SGs). Reverse phase-high performance liquid chromatography (HPLC) of rat
      SGs extracts revealed the presence of the 28-amino-acid (AA) circulating peptide
      ANP (Ser99-Tyr126) and the 126-AA prohormone (Asn1-Tyr126). The presence of ANP
      prohormone indicated that SGs are a site of ANP synthesis. Indeed, ANP mRNAs were
      demonstrated. ANP mRNA was 10 times lower than in the lung and only about 7 times
      lower than in the hypothalamus. ANP content in SG was determined as 30 +/- 8
      ng/mg of protein (n = 7). In addition the presence of another member of the
      natriuretic peptide family, C-type natriuretic peptide (CNP), was found in SG.
      The CNP level of 293 +/- 38 pg/mg protein was significantly higher than in the
      lungs (44 +/- 6 pg/mg protein, P < 0.001, n = 5), but about 15 times lower than
      in hypothalamus (4.5 +/- 0.6 ng/mg protein, P < 0.001, n = 6). Both guanylyl
      cyclase and clearance receptors were expressed in SG. The presence of natriuretic
      peptide transcripts and their receptors suggests a role in rat SG functions.

PMID- 8738884
TI  - Where do we go in occupational neuroepidemiology?

PMID- 8738885
TI  - Health risks of electric and magnetic fields caused by high-voltage systems in
      Finland.
AB  - Health risks of power-frequency electric and magnetic fields (EMF) in the
      generation and transmission of electric power were investigated in a program
      comprising nine separate projects. The central objectives were to assess the
      practical importance of electric and magnetic field exposure as a health risk, to
      produce data applicable to field management measures at a major power company,
      and to support and spur research activities on electric and magnetic fields as
      environmental agents. Electric and magnetic fields seemed to be weak
      environmental factors, but the findings were uncertain and controversial as to
      the health risks except that, electric field strengths (about 1.5 kV.m-1) found
      even in the vicinity of 110 kV power lines may cause interference with cardiac
      pacemakers. There is still a need, however, for further basic research focused on
      the interaction mechanisms of electric and magnetic fields and biological tissue.

PMID- 8738886
TI  - Maximizing accuracy and precision using individual and grouped exposure
      assessments.
AB  - OBJECTIVES: Random errors in exposure data were explored to determine their
      effect on exposure-response relationships using individual, grouped, or combined
      (grouped and individual) exposure assessment methods. METHODS: Monte Carlo
      simulations were conducted by generating small "studies" of one hundred subjects
      divided into four exposure groups. Observed exposure data were generated for each
      individual using assumed inter- and intraindividual variances and a lognormal
      distribution. The data were used to calculate the following three estimates of
      exposure: an individual mean, a group mean, and a hybrid estimate using the James
      Stein shrinkage estimator. The exposure estimates were regressed on generated
      (continuous) "health outcomes," and the regression results were stored and
      analyzed. RESULTS: Random errors in exposure data resulted in attenuation of the
      exposure-response relationship when the individual estimates were used,
      especially when the within-subject variability was high. The attenuation was
      substantially controlled by the group mean estimate, however, at a cost of
      decreased precision. The hybrid estimator simultaneously controlled both bias and
      imprecision in the observed exposure-response function. CONCLUSIONS: While
      estimates of exposure based on individual means may result in attenuation of the
      exposure-response relationship, grouped estimates may control bias while
      decreasing precision. Combining individual and group estimates can simultaneously
      control both types of error. However, further research is required to determine
      how robust these findings are to different error structures, grouping strategies,
      exposure-response models, and exposure assessment methods.

PMID- 8738887
TI  - Improved nasal clearance among pulp-mill workers after the reduction of lime
      dust.
AB  - OBJECTIVES: The purpose of this study was to investigate nasal symptoms and
      function among workers exposed to lime dust and to determine if a reconstruction
      of the workplace improved the worker's nasal health. METHODS: In 1992, pulp-mill
      workers (N = 15) exposed to lime dust and an equal number of matched unexposed
      referents were examined by questionnaires, nasal peak expiratory flow, the
      saccharin test, nasal lavage, and a clinical examination of the upper airways.
      The study was repeated one year later, after the pulp mill had been rebuilt. Dust
      levels were measured on both occasions with stationary and personal samplings.
      RESULTS: In 1992 the total dust level was 1.2 mg.m-3. The saccharin test showed a
      significantly increased nasal transit time for the exposed workers in comparison
      with that of the unexposed referents (difference 3.5 min, 95% confidence interval
      0.1-6.9 min). One year later the dust levels had decreased to 0.1 mg. m-3, and
      the difference in nasal transit time had decreased (difference- 0.8 min, 95%
      confidence interval -4.8-3.3 min). CONCLUSIONS: Workers exposed to lime dust have
      an impaired mucociliary function. This impairment is probably due to the
      alkalinity of the lime. When dust levels are reduced, mucociliary function
      improves; therefore renovating a workplace to reduce dust levels has a positive
      effect.

PMID- 8738888
TI  - Malignant melanoma among lithographers.
AB  - OBJECTIVES: Mortality studies have suggested that workers in the printing
      industry may have a higher incidence of malignant melanoma. The aim of this study
      was to assess the incidence of malignant melanoma among lithographers. METHODS: A
      cohort of 837 lithographers, born in 1933-1942, was followed in the Danish Cancer
      Register from 1974 to 1989. RESULTS: Five cases of malignant melanoma were found,
      with 1.5 expected (relative risk 3.4, 95% confidence interval 1.2-7.5).
      CONCLUSIONS: Many known and suspected carcinogens are used in the printing
      industry. Hydroquinone, used for photographic development, may be implicated in
      the observed increase in risk, as it causes depigmentation and changes in
      melanocytes in the skin.

PMID- 8738889
TI  - Partition coefficients between human blood or adipose tissue and air for aromatic
      solvents.
AB  - OBJECTIVES: The partitioning of lipophilic toxicants into blood and into adipose
      tissue plays an important role in the physiological distribution and toxicology
      of these substances. The partition coefficients between blood and air and adipose
      tissue and air were determined for widely used aromatic solvents in an in vitro
      test system using human tissue samples. METHODS: Samples of whole venous blood (N
      = 35) were drawn from 10 subjects. In addition, samples of perirenal and
      epididymal adipose tissue were obtained from F344 rats, along with subcutaneous,
      omental, or inguinal adipose tissue from 43 patients who had undergone surgery.
      Portions of each tissue were injected into vials for equilibration with
      atmospheres containing deuterated and nondeuterated organic solvents. Gas
      chromatographic headspace analysis was then used to determine the partition
      coefficients between blood and air and adipose tissue and air. RESULTS: The mean
      partition coefficients between human blood and air or adipose tissue and air were
      334 (SE 11) (adipose tissue) for benzene; 1764 (SE 49) (adipose tissue) for
      ethylbenzene; 3184 (SE 84) (adipose tissue) for styrene; 18.3 (SE 0.24) (blood)
      and 962 (SE 32) (adipose tissue) for toluene; 35.2 (SE 0.45) (blood) and 2460 (SE
      63) (adipose tissue) for O-xylene; 31.9 (SE 0.45) (blood) and 1919 (SE 53)
      (adipose tissue) for m-xylene; and 39.0 (SE 0.70) (blood) and 2019 (SE 102) for p
      xylene. Regression analyses revealed coefficients of determination of 0.88
      (human) and 0.98 (rat) between blood and air and log tissue and air. A value of
      0.98 was found for partition coefficients between rat and human adipose tissue.
      CONCLUSIONS: The partition coefficients between blood and air and adipose tissue
      and air were strongly correlated. The partitioning of aromatic solvents into rat
      adipose tissue is predictive of partitioning into human adipose tissue.

PMID- 8738891
TI  - Effect of overtime work on cognitive function in automotive workers.
AB  - OBJECTIVE: The present investigation examined whether increased overtime work
      predicts impairment in cognitive performance in the domains of attention,
      executive function, and mood. METHODS: The behavioral and cognitive functions of
      248 automotive workers were measured by a neurobehavioral test performance.
      Overtime, defined as number of hours worked greater than 8 h a day or greater
      than 5 d a week, was calculated from company payroll records for the week before
      the test day. The number of consecutive days worked before the test day was also
      determined. RESULTS: Cross-sectional data analysis by multiple linear regression,
      after adjustment for the effects of age, education, gender, alcohol intake,
      repeated grade in school, acute petroleum naphtha exposure, shift worked, job
      type, number of consecutive days worked before the test day, and number of hours
      worked on the test day before the testing, demonstrated that increased overtime
      was significantly associated with impaired performance on several tests of
      attention and executive function. Increased feelings of depression, fatigue, and
      confusion were also associated with increased overtime work. In addition
      significant interaction effects were observed for job type but not for naphtha
      exposure. CONCLUSIONS: The findings support the hypothesis that overtime work
      results in impaired cognitive performance in the areas of attention and executive
      function and that both overtime hours and the number of consecutive days worked
      prior to a test day affect mood.

PMID- 8738890
TI  - Quantitative magnetic resonance imaging and the electrophysiology of the carpal
      tunnel region in floor cleaners.
AB  - OBJECTIVES: The purpose of this study was to evaluate possible structural changes
      of the wrist and subclinical damage in the median nerves of healthy floor
      cleaners. METHODS: Twenty-four cleaners and 19 referents (noncleaners), all
      women, underwent bilateral magnetic resonance (MR) wrist examination and nerve
      conduction studies. They were all randomly selected from an occupational health
      service. From MR images the volumes of the wrist, carpal tunnel, and thenar and
      hypothenar muscles were calculated, as well as the signal intensity of the median
      nerve, bilaterally. RESULTS: No significant difference in the volume of the
      carpal tunnel was found in the two groups. The relative signal intensity of the
      median nerve was 0.55 for the cleaners and 0.48 for the referents (P = 0.05). The
      mean nerve conduction velocity values were 55.2 m.s-1 for the right median nerve
      of the cleaners and 57.4 m.s-1 for the right median nerve of the referents (P =
      0.03). The median nerve of the cleaners had a mean sensory amplitude of 128.2
      microV compared with 162.8 microV for the referents (P = 0.01). There was a
      tendency towards a longer distal latency of the median nerve in the cleaner
      group. CONCLUSIONS: This study revealed subclinical intrinsic damage to the
      median nerve, as demonstrated by MR, and poorer electrophysiological nerve
      function among workers at high risk (cleaners) compared with workers at lower
      risk (noncleaners).

PMID- 8738892
TI  - Circadian adjustment of men and women to night work.
AB  - OBJECTIVES: The aims of the present study were to define the adjustment of sleep
      wakefulness and other circadian rhythms during consecutive night shifts and to
      study the effect of gender on the adjustment to night work. METHODS: Twenty
      experienced shift workers, 9 men and 11 women, were studied under controlled
      laboratory conditions. After a night of habituation, the subjects worked one day
      shift and three night shifts. Rectal temperature was measured continuously during
      the study. Salivary melatonin and cortisol were assessed at 2-h intervals, and
      subjective sleepiness was checked every hour during the work shifts. Sleep was
      registered by the static-charge sensitive bed (SCSB) method after the workshifts.
      RESULTS: Subjective sleepiness varied both between the work shifts and between
      the men and women. The subjects felt most alert during the day shift and were the
      sleepiest during the first night shift. Sleepiness decreased during the
      consecutive night shifts but did not reach the level of the day shift during the
      three nights. The sleepiness of the women decreased more than that of the men,
      the difference being significant during the second and third night shifts (P <
      0.05). The circadian rhythm of body temperature, salivary cortisol, and time in
      bed changed significantly (P < 0.05) between the workshifts, but no differences
      were found between the men and women in the circadian adjustment of the
      physiological variables to night work. CONCLUSIONS: The men felt sleepier than
      the women during the consecutive night shifts, although no physiological
      differences were found between the genders. However, since normal social and
      domestic factors were excluded, the findings cannot be considered as evidence of
      women's better adaptation to night work in everyday life.

PMID- 8738893
TI  - Job strain and psychological distress in white-collar workers.
AB  - OBJECTIVES: In line with Karasek's job strain model, the objective of the study
      was to determine whether workers submitted to high job strain, a combination of
      high psychological demand and low decision latitude, develop more psychological
      distress than workers not submitted to high job strain. A second objective was to
      determine whether social support at work modifies the association between job
      strain and psychological distress. METHODS: The design was cross-sectional and
      included white-collar workers in the Quebec city area. A self-administered 26
      item questionnaire (the Job Content Questionnaire) measured psychological demand,
      decision latitude, and social support at work. Psychological distress was
      measured by the Psychiatric Symptom Index, a 14-item self-administered
      instrument. RESULTS: Among the 2889 participants, the prevalence of psychological
      distress was 27.8%. High job strain was present in 20.5% of the subjects. The
      crude odds ratio (OR) of high job strain with psychological distress was 3.52
      [95% confidence interval (95% CI) 2.54-4.88]. The OR adjusted for age, gender,
      employment status, occupation, social support at work, nonwork social support,
      cynicism, hostility, domestic load, and stressful life events during the last 12
      months was still significant (OR 2.45, 95% CI 1.66-3.62). CONCLUSIONS: Our
      results support the association between job strain and psychological distress.
      Social support at work, although significantly associated with psychological
      distress, did not modify the association between job strain and psychological
      distress.

PMID- 8738894
TI  - Diabetes mellitus among Swedish art glass workers--an effect of arsenic exposure?
AB  - OBJECTIVES: The purpose of this study was to search for evidence of an
      association between occupational arsenic exposure and diabetes mellitus, as
      implied by the relation of this disease to arsenic in drinking water in a recent
      study from Taiwan. METHODS: A case-referent analysis on death records of 5498
      individuals in the art glass producing part of southeastern Sweden was performed.
      Out of all the enrolled subjects, 888 were glass workers. According to
      occupational title, glassblowers, foundry workers, and unspecified workers were
      regarded as potentially exposed to arsenic. Persons with a diagnosis of diabetes
      mellitus either as an underlying or contributing cause of death were considered
      cases. Referents were decedents without any indication of cancer, cardiovascular
      disease, or diabetes. RESULTS: A slightly elevated risk [Mantel-Haenszel odds
      ratio (MH-OR) 1.2, 95% confidence interval (95% CI) 0.82-1.8] was found for
      diabetes mellitus among the glassworks employees, especially in combination with
      cardiovascular disease (MH-OR 1.4, 95% CI 0.81-2.3). For the glassblowers, other
      foundry workers and unspecified glassworkers probably exposed to arsenic, the M-H
      odds ratio was 1.4 (95% CI 0.92-2.2). Unspecified glass workers, who probably
      included persons with high exposure, carried the higher risk (MH-OR 1.8, 95% CI
      1.1-2.8). CONCLUSIONS: The observations from this study provide limited support
      for the possibility that occupational arsenic exposure could play a role in the
      development of diabetes mellitus. Many other metallic compounds are also used in
      art glass production, however, and there is a possibility of confounding.

PMID- 8738895
TI  - Elevated urinary cadmium concentrations in a patient with acute cadmium
      pneumonitis.
AB  - BACKGROUND: Acute serious inhalation of cadmium fumes often causes chemical
      pneumonitis or metal fume fever. Because symptoms of both diseases begin several
      hours after exposure and closely mimic each other, one often mistakes chemical
      pneumonitis for metal fume fever in the early stages. It is, however, essential
      to differentiate between the two since chemical pneumonitis can progress to
      serious consequences. CASE: A 43-year-old man was admitted to the hospital 2 d
      after exposure to cadmium fumes. The initial diagnosis was metal fume fever on
      the basis of his history, and he was treated accordingly. His symptoms worsened
      however, and transient renal impairment was identified as consistent with cadmium
      induced renal toxicity. Although the possibility of drug-induced renal damage
      could not be excluded, abnormal urinalysis findings on admission suggested that
      the renal tubular damage was caused by inhaled cadmium before admission.
      CONCLUSIONS: Measuring the urinary cadmium concentration is an effective method
      for confirming acute cadmium poisoning.

PMID- 8738896
TI  - IARC evaluates printing processes and printing inks, carbon black and some nitro
      compounds.

PMID- 8738897
TI  - Nasal receptors responding to cold and l-menthol airflow in the guinea pig.
AB  - The aim of this study was to demonstrate the presence of nasal 'cold' receptors,
      through recordings of action potentials from the ethmoidal nerve (EN), in guinea
      pigs and to characterize their responsiveness to l-menthol and capsaicin.
      Constant flows (400 ml/min) of room air (20 degrees C), warm air (45 degrees C),
      room air containing l-menthol, and cold air (-5 degrees C) were directed into the
      nasal cavity in the inspiratory direction via a nasopharyngeal catheter in the
      anesthetized guinea pigs breathing spontaneously through a tracheostomy. The
      ethmoidal afferent activity was increased by cold air, and to a greater extent by
      l-menthol but hardly by warm air. After topical anesthesia of the nasal cavity
      with 2% lidocaine, cold air and l-menthol no longer stimulated the EN. L-menthol
      noticeably stimulated the EN even after repeated capsaicin instillation into the
      nose, but these values were lower than those following the l-menthol stimulus
      before the 1st capsaicin treatment. These results suggest that the ethmoidal
      nerve in guinea pigs has cold-sensitive receptors which consist of both small
      myelinated fibers and C-fiber endings.

PMID- 8738898
TI  - Relief of the 'air hunger' of breathholding. A role for pulmonary stretch
      receptors.
AB  - Fowler (Fowler, W.S., 1954, J. Appl. Physiol. 6:539-545) showed that rebreathing,
      despite worsening PCO2 and O2 saturation, relieved the distress of breathholding;
      he suggested a role for vagal input in the relief. We studied effects on
      respiratory sensation of breathholding and rebreathing in normals, patients with
      bilateral lung transplants (LT), who have a decrease in number of pulmonary
      stretch receptors (PSR), and heart transplant recipients (HT). Subjects held
      their breath until distress became intolerable, rebreathed various combinations
      of CO2 and O2, then performed another maximal breathhold. Respiratory distress
      was rated continuously (visual analog scale) by each subject. Both LT and HT had
      earlier onset of and more rapidly developing distress during breathholding,
      resulting in shorter breathhold times, than normals. Relief with rebreathing was
      neither as rapid nor as great in LT as in HT and normals. Our findings suggest
      that mechanisms that produce respiratory distress in HT and LT are similar, but
      differ from normals. However, reduction in distress on rebreathing is more rapid
      and greater in HT and normals than in LT. This is compatible with the loss during
      rebreathing of the inhibitory effect of PSR input on neural mechanisms that lead
      to respiratory distress.

PMID- 8738899
TI  - How does positive end-expiratory pressure decrease CO2 elimination from the lung?
AB  - Six chloralose-urethane anesthetized dogs (23 +/- 2 kg) underwent median
      thoracotomy (open pleural spaces) and constant mechanical ventilation with O2. We
      conducted measurements at baseline and during 25 min of ventilation with 3.3
      cmH2O positive end-expiratory pressure (PEEP3) or 10.7 cmH2O PEEP (PEEP 11),
      including breath-by-breath values in the first 2 min after PEEP began. PEEP 11
      immediately decreased pulmonary CO2 elimination per breath (VCO2,br, digital
      integration and multiplication of exhaled flow and FCO2) from 8.4 +/- 2.0 to 4.5
      +/- 1.6 ml (P < 0.05) by significantly decreasing alveolar ventilation (VA) (29%
      increase in anatomical dead space (VDana) and generation of high VA/Q regions)
      and by decreasing alveolar PCO2 (PACO2) from 42.5 +/- 3.5 to 35.9 +/- 3.5 Torr
      (decreased CO2 transfer to the lung as electromagnetic aortic cardiac output (QT)
      decreased by 51%). The immediate dilution of alveolar gas and PACO2 by fresh gas
      as PEEP increased functional residual capacity by 1152 +/- 216 ml was offset by
      simultaneous decreased expiratory volume and, hence, CO2 accumulation. Compared
      to baseline, the 17% reduction in VCO2,br was sustained at 25 min after addition
      of PEEP 11 because VA remained depressed. Then, VCO2,br could only be restored to
      baseline if PACO2 sufficiently increased. However, CO2 transport was still in
      unsteady state at 25 min of PEEP. Peripheral tissue retention of CO2 and the
      significant increase in mixed venous PCO2 (PVCO2, 62.4 +/- 6.2 Torr) were not
      enough to normalize CO2 transfer to the lung and to sufficiently increase PACO2,
      especially during the continued depression in QT that occurred at higher PEEP.
      The sustained decrease in VCO2,br during PEEP was not mirrored by changes in end
      tidal PCO2 (PETCO2).

PMID- 8738900
TI  - Structural determinants of maximal O2 transport in muscles of exercising foxes.
AB  - The arctic blue fox (Alopex lagopus) has a specific maximal oxygen consumption
      (VO2 max/Mb = 3.6 ml O2.s-1.kg-1) that is approximately 1.6-fold greater than
      those of dogs and horses. The fox has one of the highest body mass specific
      skeletal muscle mitochondrial volumes (V(mt,m)/Mb = 44 cm3.kg-1) among mammalian
      athletic species matching its higher VO2 max/Mb. The structural components
      related to capillaries, such as specific capillary length density (J(c)/Mb = 348
      km.kg-1) and specific capillary volume (V(c)/Mb = 4.8 ml.kg-1), are not greater
      in the fox than in the larger athletes. Because a greater specific muscle
      diffusing capacity for oxygen (DTO2/Mb) is not utilized by the fox to achieve a
      higher VO2 max/Mb, a higher pressure difference for diffusion in the muscle
      capillaries is the alternative explanation for the fox's higher VO2 max/Mb. This
      mechanism is suggested by the fox's higher arterial and mixed venous capillary
      PO2 (120 mm Hg and 37 mm Hg, respectively) and its shorter mean muscle capillary
      transit time for blood (tc = 0.28 sec) compared to larger species.

PMID- 8738901
TI  - Increased response to antigen and histamine release in smaller sensitized canine
      bronchi.
AB  - We studied the Schultz-Dale response in vitro in large and small size branches
      from 3rd to 6th generation bronchi from ragweed-sensitized dogs. The response to
      electric field stimulation (EFS) increased after antigen from 65.56 +/- 8.11 to
      78.6 +/- 9.0 mN/mm2 of smooth muscle (P < 0.01), but no topographical difference
      was observed. The response to ragweed (% of the response to EFS) was 158.3 +/- 12
      and 67.1 +/- 11.7 in strips from small and large branches respectively (P <
      0.01), while no difference was observed between generations; when clustering
      bronchi according to dimension, it was 129.9 +/- 13.4 in small and 71.9 +/- 19.8
      in large bronchi (P < 0.01). Histamine released from small and large branches was
      2.90 +/- 1.01 and 0.76 +/- 0.20 (ng/mg of tissue) respectively (P < 0.05); no
      difference was found between generations. In conclusion, in sensitized dogs a
      greater response to antigen, which involves a higher histamine release, occurs in
      small compared to large bronchi. We suggest that control of distribution of
      ventilation occurs mainly at small bronchi level, which becomes the elective
      tissue to study the Schultz-Dale response. Finally, the classification of bronchi
      into generations is inadequate to study allergic bronchospasm.

PMID- 8738902
TI  - The ventilatory and metabolic response to hypercapnia in newborn mammalian
      species.
AB  - Conscious newborns of 12 species from 4 mammalian orders, ranging in body mass
      (M) from 1 g (mouse) to 5 kg (deer), were studied during air and during 5% CO2
      breathing. The interspecies relationship between oxygen consumption (VO2) and M
      was the same in air and hypercapnia, in both cases VO2 alpha M 0.90; on average,
      hypercapnic VO2 was 101% of the air value. In 5% CO2, ventilation (VE) increased
      in all newborns, mostly because of the increase in tidal volume (178%), whereas
      breathing rates averaged 98% of the air values. The hyperpnea during CO2 was
      slightly greater in the larger newborns. Body temperature was not altered by CO2
      breathing. We conclude that the average respiratory response of the newborn to
      moderate hypercapnia is a hyperventilation different from that of the neonatal
      mammal in acute hypoxia (Mortola et al., Respir. Physiol. 78: 31-43, 1989). In
      fact, hypercapnic hyperventilation resulted only from the hyperpnea, with no
      hypometabolic contribution, and the hyperpnea reflected the increase in tidal
      volume, with no change in rate. It is also concluded that the neonatal
      hypometabolic response is specific to hypoxia, and not an undifferentiated
      response to chemoreceptors stimulation.

PMID- 8738903
TI  - Differing patterns of mechanical response to direct fetal hormone treatment.
AB  - A single combined intramuscular dose of betamethasone and l-thyroxine (T4) or
      placebo was injected into the shoulder of fetal lambs 48 hours prior to delivery
      at days 121 (n = 14), 128 (n = 25) or 135 (n = 20) of gestation. Respiratory
      mechanics were calculated using multiple linear regression analysis. Both
      respiratory system resistance (RRS) and elastance (ERS) decreased approximately 4
      fold between gestational days 121 (D121) and 135 (D135). Both variables were also
      reduced by hormone treatment. Reduction in ERS was due to a reduction in both
      lung (EL) and chest wall (EW) components. In absolute terms EW decreased with
      gestational age; however, EW as a proportion of total elastance (% EW) increased.
      Inclusion of a volume-dependent elastance term in the multiple linear regression
      model enabled us to separate total elastance into volume-independent (E1) and
      volume-dependent (E2V) components. E1 decreased almost 8-fold compared with only
      a 2.5-fold fall in E2V between D121 and D135. %E2, the proportion of ERS which is
      volume-dependent and which provides an index of overventilation, doubled over
      this time period. Hormone treatment affected E1 and E2V components equally hence
      %E2 was not altered. Both excised lung volume and end expiratory alveolar volume
      increased with gestational age and with treatment. The response to treatment was
      qualitatively similar at each of the gestational ages examined, however, for all
      mechanics variables, except resistance and E1, the magnitude of response to
      treatment was significantly smaller in D135 animals compared with other age
      groups.

PMID- 8738904
TI  - Dental conditions and temporomandibular joints in an early mesolithic bog man.
AB  - In 1994 parts of a human skeleton were found in the county of Vastergotland,
      Sweden. The remains were probably from a man and estimated according to 14C
      dating to be about 9800 years old, i.e. from the Early Mesolithic Period. As such
      old finds are rare and the skull was well preserved a more detailed description
      is presented in this paper. The facial skeleton was robust and the face shape was
      rectangular. The remaining teeth, one maxillary and 10 mandibular teeth,
      exhibited no caries but extensive occlusal wear which in some teeth had exposed
      the pulp and led to periapical osteitis. Besides these teeth the 4 maxillary
      incisors and the two canines and one incisor in the mandible had been lost post
      mortem, probably because of severe marginal bone loss. Both temporomandibular
      joints showed remodelling, one also osteoarthrotic changes. The observations are
      discussed with respect to masticatory function and some background factors.

PMID- 8738905
TI  - Incidence of traumatic tooth injuries in children and adolescents in the county
      of Vastmanland, Sweden.
AB  - The study reports the total incidence as well as the incidence of different types
      of traumatic tooth injuries in a Swedish county in the age interval 0-19 years
      during 1989/90. The incidence of individuals experiencing tooth injuries was 13
      per 1000 per year. Boys were more frequently injured in the age-groups 3-4 years
      and 7-9 years and girls, in the age-group 5-6 years. A method is presented
      defining uncomplicated and complicated tooth injuries as a basis for estimating
      the economic consequences of these injuries in the community. Boys more often
      suffered uncomplicated injuries to permanent teeth and girls, to primary teeth (p
      < 0.05). The same distribution was found for uncomplicated multiple tooth
      injuries. Boys sustained more uncomplicated hard tissue injuries and girls, more
      uncomplicated luxation injuries (p < 0.01). Using a classification according to
      the most serious tooth injury in each episode, 33% of the episodes had resulted
      in complicated injuries in which the pulpal tissue and/or periodontal membrane
      was severely damaged.

PMID- 8738906
TI  - Midazolam intravenous conscious sedation in oral surgery. A retrospective study
      of 372 cases.
AB  - In 1987 the Swedish Dental Act was amended to allow Swedish dentists who have
      undergone a specific accreditation course to administer intra-venous sedation.
      Midazolam is a benzodiazepin derivate with express sedative and hypnotic
      qualities, powerful amnesia, a short half-life time and few secondary effects.
      From 1989-1994 midazolam intravenous conscious sedation (ICS) was administered in
      372 cases in the Department of Oral and Maxillofacial Surgery, County Hospital,
      Falun. This study presents data on the 298 patients. Although surgical removal of
      impacted wisdom teeth predominated, implant surgery, reduction of fractures and
      correction of anomalies were also carried out. Supplementary sedative
      premedication was rarely used. Most patients were treated under local
      anaesthesia. The mean dosage was 10.45 mg (range 1.25-40 mg). Mean dosage/kg was
      0.15 mg (range 0.03-0.50 mg). The average duration of anaesthesia was 50 minutes.
      The average recovery time was 94 minutes. Three hundred and sixty-nine of 372
      planned treatments were completed. No serious complications occurred. The
      patients were co-operative during surgery and were satisfied with the treatment.
      Compared with full anaesthesia this method required less resources and is a
      valuable complement in management of anxious patients undergoing oral surgery.

PMID- 8738907
TI  - Orthodontic care provided by general practitioners and specialists in three
      Swedish counties with different orthodontic specialist resources.
AB  - Three counties in Sweden (A, G, and W) with free orthodontic care and different
      orthodontic resources and geographic structures were studied in 1987. Samples of
      totally 942 young adults (mean age 18.8 years, SD 0.44) were examined concerning
      malocclusions and all orthodontic treatment provided by general practitioners or
      by orthodontic specialists. The care in a rural area (county G) with abundant
      specialist resources was based on specialist treatments easy assessable to the
      patients and supplemented by treatments, mainly without appliances and provided
      by general practitioners. There was a generous attitude of consultation with
      specialists and of providing treatment. The sparsity of specialist resources had
      in an urban area (county A) resulted in a greater restriction on providing
      treatments. The treatments were performed in a higher age and were, to a greater
      extent, not completed by the age of 19, and a smaller percentage of individuals
      were treated than in the other two counties. The care in a large rural area
      (county W) with long distances to the only specialist clinic was based on
      treatments provided by general practitioners. In spite of the few specialist
      resources there was a generous attitude of providing treatments. Interceptive
      methods were used to a great extent, and later completed with appliance therapy.
      According to a treatment priority index 44% of the untreated individuals in the
      three counties had malocclusions and an objective treatment need, and there were
      no significant differences between the counties. Regardless of differences in
      specialist resources and structure of the free public orthodontic care, a
      substantial and equal proportion of the untreated individuals in the counties had
      malocclusions with treatment need, but they had no treatment desire.

PMID- 8738908
TI  - Orthodontic treatment outcome in three Swedish counties with different
      orthodontic resources.
AB  - The orthodontic treatment outcomes of 350 19-year-old individuals in three
      Swedish counties (A, G, and W) with different orthodontic resources and
      geographic structures were analyzed. The aim was to evaluate the qualitative
      outcome of orthodontic treatment provided by general practitioners or
      specialists. In a small rural area (county G), with most specialist resources,
      the standard of the treatments was high in both specialist treated as well as in
      nonspecialist treated individuals. The possibilities for the specialists to
      supervise the nonspecialist care and to treat individuals in need of specialist
      treatment were good. In an urban area (county A), with less specialist resources
      (than county G), the standard of the treatments provided by the specialists was
      high, and higher than the untreated individuals in the same county. The standard
      of the treatments provided by general practitioners was, however, low. The lack
      of specialist resources had implied a greater restriction on starting treatments,
      and the treatments were performed in a higher age than in the other two counties.
      In a large rural area (county W), with the fewest specialist resources, the
      standard of the treatments was in general lower than in the other two counties
      and did not attain the standard of the untreated individuals in county W.
      Attempts to compensate for a sparsity of orthodontic specialists by an extended
      engagement of general practitioners resulted in a generous attitude of providing
      orthodontic treatments, and a lower standard of the treatments in general. The
      orthodontic treatments substantially improved the malocclusions, especially
      treatments provided by specialist. The standard of the treatments in the counties
      showed a good correlation with the available resources in terms of orthodontic
      specialists and the ability to supervise the treatments of general practitioners.
      The lack of sufficient supervision of non-specialist orthodontic treatment had
      negative influence on the quality.

PMID- 8738910
TI  - Dentists' work location in relation to their origin.
AB  - The aim of this study was to map dentist' work location and put it in relation to
      the place where they went to secondary school. All dentists in Sweden who
      graduated from Swedish dental schools in 1983/84, 1984/85 and 1985/86 were
      studied. For all these the place where they went to secondary school and the
      place where they work as dentists were registered. Sweden was divided into 14
      areas: central, middle and remote with respect to urbanisation, location of
      dental schools etc. All dentists were placed in one of the 14 areas according to
      their secondary school education and where they worked as active dentists. This
      clearly showed that dentists very often go back to the area where they have had
      their secondary school education.

PMID- 8738909
TI  - Dental development, dental age and tooth counts. A prospective longitudinal study
      of Pakistani children.
AB  - A sample of 443 Pakistani infants from four different socioeconomic areas was
      followed longitudinally study the emergence of the primary teeth. The mean ages
      of emergence of the primary teeth, without regard what kind of tooth and dental
      ages of the primary teeth were calculated. The subjects showed no sexual
      dimorphism in the emergence times of the primary teeth. The children from poor
      areas. were ahead by statistically significant differences from upper middle
      class, for emergence of the primary teeth 17-20. On comparison with Swedish
      standards (Hagg & Taranger, 1985) Pakistani children are delayed, by a
      statistically significant difference, in the emergence of primary teeth 1-16,
      however, they were at par in the emergence of 17-20 primary teeth.

PMID- 8738911
TI  - Introduction: what mechanism(s) drive hypermutation?

PMID- 8738912
TI  - The mechanism of somatic hypermutation studied with transgenic and transfected
      target genes.
AB  - Somatic hypermutation of Ig genes is beginning to be understood in molecular
      terms. Ig transgenes have served as model test genes and been shown to mutate,
      just as endogenous genes, with a peak of mutation over the VJ region and a
      sparing of the C region. The levels of somatic mutation appear to be related to
      the expression of the transgenes. DNA hypermethylation of modified Ig transgenes
      interferes with both expression and somatic hypermutation. Test substrates
      consisting of bacterial lacZ alpha or supFtRNA inserted within x transgenes were
      shown to be rescuable as expressible bacterial plasmids, but did not seem to be
      targeted. A synthetic sequence consisting of alternating restriction enzyme
      sites, that cannot be subject to methylation, was found to be a reliable
      transgenic substrate for easy assay of somatic mutation. The generation of a
      transgenic mouse with a x transgene in which the transcriptional promoter has
      been duplicated upstream of the C region has given new clues to the mutation
      mechanism. In this transgene, transcripts initiate from both the C region and the
      V region promoters, and both regions, but not the sequences between them, are
      hypermutated. These results suggest that somatic hypermutation is linked to the
      initiation of transcription. A model is proposed in which somatic mutation is
      dependent on transcription coupled DNA repair.

PMID- 8738913
TI  - Characterization of the cis-acting elements required for somatic hypermutation of
      murine antibody V genes using conventional transgenic and transgene homologous
      recombination approaches.
AB  - We have used conventional transgenic technology and a novel transgene homologous
      recombination pathway to investigate the cis-acting elements necessary for murine
      antibody V-gene somatic hypermutation. These studies show that an undefined
      element 3' of the IgH intronic enhancer is required for VH hypermutation. This
      element appears not to be the 3' alpha IgH enhancer, at least in its "minimal'
      form. Elements 5' of the natural VH promoter are not necessary for hypermutation,
      and this promoter can be replaced by a non-Ig promoter, resulting in a reduction,
      but not ablation of the rate of hypermutation in the adjacent VH gene. Our
      analyses provide no support for "gene conversion' models of hypermutation, and
      support models that propose a role for transcription in hypermutation over purely
      DNA-based models. Analysis of a CD72/kappa chimeric transgene suggests that all
      of the factors that influence hypermutation of kappa transgenes have yet to be
      defined.

PMID- 8738914
TI  - Gene conversion and homologous recombination in murine B cells.
AB  - Gene conversion has been found to be important in the diversification of antibody
      genes in chickens and in rabbits. In other species, however, it is not clear
      whether gene conversion plays any role in antibody diversity. Analysis of an H
      chain antibody gene construct that was designed to optimize the detection of gene
      conversion events in transgenic mice has shown that sequence transfers that
      resemble gene conversion events can occur in murine B cells and are associated
      with somatic hypermutation. This raises the possibility that an error-prone gene
      conversion mechanism might play a role in murine somatic hypermutation.

PMID- 8738915
TI  - The targeting of somatic hypermutation.
AB  - Somatic hypermutation does not occur randomly within immunoglobulin V genes but,
      rather, is preferentially targeted to certain nucleotide positions (hot spots)
      and away from others (cold spots). Cold spots often coincide with residues
      essential for V gene folding. Hotspots, which appear to be strategically located
      to favour affinity maturation, are most frequently located in the CDRs
      (particularly CDR1) though conserved hotspots are also found at the base of FR3.
      Hotspots are in part created by local DNA sequence and the strong biases of codon
      usage in V genes indicate that the genes have evolved such that somatic
      hypermutation is targeted to those parts of the V where it is likely to prove
      most useful. These features of mutational hotspots and biased codon usage are
      also evident in V genes of lower animals suggesting that diversification by
      strategic targeting of non-templated mutation may have evolved early in antigen
      receptor evolution.

PMID- 8738916
TI  - Sequential triggering of apoptosis, somatic mutation and isotype switch during
      germinal center development.
AB  - Using an approach similar to that used to study primary B-lymphocyte development
      within bone marrow and primary T-lymphocyte development within thymus, the
      peripheral B-cell maturation pathway within secondary lymphoid tissue (human
      tonsils) was analysed on the expression of discrete surface antigens. sIgD and
      CD38 permit the identification of four subpopulations of tonsillar B lymphocytes,
      including sIgD+ CD38-, sIgD+, CD38+, sIgD-CD38+ and sIgD-CD38- B cells. Further
      phenotypic, functional and Ig gene analysis (IgV gene sequences, expression of
      sterile transcripts and DNA switch circles) allowed us to conclude the following:
      (1) sIgM+ IgD+ CD38- B cells are naive B cells (Bm1 + 2), which carry unmutated
      antigen-receptors; (2) sIgM+ IgD+ CD38+ B cells are germinal center founder cells
      (Bm2'), which become prone to undergo apoptosis before the onset of somatic
      mutation; (3) sIgM-IgD+ CD38+ are germinal center B cells (Bm 3 delta), that have
      accumulated the highest number of somatic mutations ever reported in normal B
      cells; these cells may have undergone C mu-deletion by homologous recombination
      through sigma mu-sigma delta sequences: (4) sIgD-CD38+ CD77+ B cells are
      centroblasts (Bm3), in which somatic mutation machinery is activated; (5) sIgD
      CD38+ CD77- B cells are centrocytes (Bm4), in which the isotype switching
      machinery is activated; (6) sIgD-CD38- cells (Bm5) represent somatically mutated
      resting memory B cells. In conclusion, human peripheral B-cell subpopulations
      corresponding to the differentiation stages before, during and after the
      triggering of apoptosis program, somatic mutation and isotype switch have been
      identified and isolated using a combination of surface markers.

PMID- 8738917
TI  - The germinal center: a crucible for lymphocyte selection.
AB  - Antigen first activates T and B lymphocytes in the T-cell areas of secondary
      lymphoid tissues where cognate- and costimulus-dependent proliferation expands
      the population of reactive lymphocytes. Selected T- and B-cell progeny from this
      population migrate into B-cell zones to form germinal centers (GC), where intense
      proliferation, apoptosis, and V(D)J hypermutation takes place. It is now known
      that each of these processes occur in both compartments of GC lymphocytes and
      that the GC T-cell represents an unusual Thy-1- subset of alpha beta T-helper
      cells that may represent a terminally differentiated cell that is lost with the
      end of the GC reaction.

PMID- 8738918
TI  - Manganese: the controversial metal. At what levels can deleterious effects occur?

PMID- 8738919
TI  - Blood manganese correlates with brain magnetic resonance imaging changes in
      patients with liver disease.
AB  - BACKGROUND: Chronic liver failure is associated with high signal abnormalities in
      the basal ganglia on T1-weighted magnetic resonance imaging of the brain. These
      abnormalities are strikingly similar to those seen following manganese
      intoxication. As dietary manganese is normally cleared by the liver, we
      hypothesize that hepatic dysfunction could lead to manganese overload and account
      for the MRI abnormalities seen in patients with chronic liver disease. METHODS:
      We measured blood manganese concentrations in eleven patients with biopsy-proven
      hepatic cirrhosis and eleven healthy age and sex-matched controls. We also
      performed semi-quantitative measures of T1 signal abnormalities on MRI in the
      patients with chronic liver disease. RESULTS: Patients with cirrhosis had
      significantly higher blood manganese concentrations (20.6 +/- 10.2 mcg/L) than
      controls (7.2 +/- 2.7, p = .0013). In addition, semi-quantitative scores of T1
      weighted signal hyperintensity on MRI correlated with blood manganese
      concentration in patients with cirrhosis (r = .65, p = .029). CONCLUSIONS: These
      findings demonstrate that chronic liver disease is associated with manganese
      overload and suggest that manganese is responsible for the T1-weighted signal
      hyperintensity seen on MRI of patients with liver disease. As manganese
      intoxication is known to cause parkinsonism and an encephalopathy similar to
      those which occur with chronic liver disease, it is possible that manganese
      toxicity contributes to the development of these symptoms in liver damaged
      patients and that therapies which prevent or reduce manganese overload may have
      clinical benefit.

PMID- 8738920
TI  - Measurement of health-related quality of life in multiple sclerosis patients.
AB  - BACKGROUND: Patient outcomes in multiple sclerosis (MS) have generally been
      measured by their neurological impairment using specific scales such as the
      Kurtzke Expanded Disability Status Scale (EDSS). However, this scale does not
      measure the multiple dimensions of health-related quality of life (HRQOL) such as
      functional status and general well-being, which are also important outcomes along
      with disease-specific measurements. METHODS: HRQOL was measured in a group of 97
      MS patients using the RAND 36-item Health Survey 1.0. The EDSS score was assigned
      by the clinic neurologist. Additional data were collected from the clinical
      record for each patient. RESULTS: MS patients scored poorly in a number of HRQOL
      domains such as physical and role functioning and energy or vitality. Disability
      as quantified by the EDSS correlated only with the physical functioning domain.
      Regression models were developed to measure the relationship between patient
      characteristics (independent variables) and HRQOL domains (dependent variables).
      DISCUSSION: A number of patient characteristics were associated with higher or
      lower scores on the HRQOL domains. Of particular interest is the finding that a
      family history of MS was associated with poorer physical and social functioning
      as well as more pain and less vitality. The occurrence of seizures had a negative
      impact on role functioning, social functioning and general health perceptions.
      HRQOL gives caregivers a broader measure of disease burden than the EDSS alone,
      and should be useful in planning and monitoring interventions.

PMID- 8738921
TI  - A novel approach to the determination and characterization of HIV dementia.
AB  - BACKGROUND: Neuropsychological studies of the pattern and extent of cognitive
      impairment in HIV-infected patients have mostly used deviations from control
      values and/or cut-off scores as criteria for classification of dementia. There
      is, however, no agreement as to how to define impairment, and classification is
      imprecise. METHOD: The current study used a dementia classification matrix,
      developed with a step-wise linear discriminant analysis of neuropsychological
      data from patients with primary neurodegenerative dementias, to classify
      symptomatic HIV patients as demented or non-demented, and further to
      differentiate cortical and subcortical dementia patterns. Thirty-two male and 2
      female patients (mean age 39 +/- 2) with symptomatic HIV disease (mean absolute
      CD4 count 195 +/- 41) participated in the study. RESULTS: Thirty-five per cent of
      patients were classified as demented. Of these, 83% showed a subcortical pattern
      and 17% a cortical profile of deficits. Significant differences between patients
      classified as subcortically demented and those categorized as normal on
      neuropsychological measures associated with subcortical integrity further
      validated the classification. Measures of psychiatric status between subgroups
      were similar. CONCLUSION: Since certain treatments may delay or reverse cognitive
      deficits, the use of an objective classification method based on discriminant
      analysis may help to identify patients who may benefit from therapy.

PMID- 8738922
TI  - A normal bias toward a pictorially defined top in line bisection.
AB  - BACKGROUND: We set out to determine whether separable visual and representational
      components underlie normal subjects' upward and distal biases in bisecting
      vertical and radial lines under visual guidance. METHODS: Thirty-four normal
      subjects were asked to bisect lines oriented horizontally, vertically, and
      radially. Human silhouette figures were placed at either end of each line. These
      figures were presented upright or upside down in order to pictorially define a
      "top" to each line independent of the actual top of the visual field. RESULTS:
      Although subjects erred toward the top of the visual field, they also
      demonstrated a significant bias toward the heads of the figures for lines in all
      spatial orientations. CONCLUSIONS: This result supports the existence of two
      biases: one toward the upper visual field, and another toward an internally
      represented "top" as suggested pictorially. These findings provide further
      support for the hypothesis that normal subjects' upward and distal biases on
      bisection of vertical and radial lines under visual guidance have both
      representational and visual-based components.

PMID- 8738923
TI  - Post-traumatic frontal lobe epilepsy with structural changes: excellent results
      after cortical resection.
AB  - BACKGROUND: The observation that resection of structural lesions of the frontal
      lobe provides an effective treatment of intractable epilepsy has been made by
      surgeons specializing in this field for over sixty years! However, the excellent
      results achieved when such resections are coupled with the use of modern
      diagnostic and operative technologies are not fully appreciated by the modern
      clinician. METHODS: We review the results of resection of large post traumatic
      frontal lesions in six patients with intractable frontal seizures. No invasive
      EEG recording was required pre-operatively. RESULTS: The imaging characteristics
      of the underlying lesions, usually due to depressed skull fractures are
      illustrated. Surgical treatment rendered five patients seizure free and the sixth
      had over 85% improvement in seizure frequency. CONCLUSIONS: Modern imaging
      permits ready visualization of the post traumatic lesions with cause intractable
      seizures. It is important to recognize that resection of these post traumatic
      scars usually leads to excellent seizure control.

PMID- 8738924
TI  - Epidemiology of childhood brain tumors.
AB  - BACKGROUND: Brain tumors comprise more than 20% of all childhood malignancies,
      and constitute the greatest number of solid pediatric cancers. Incidence rates
      reported have varied from 2.4 to 3.5/100,000 children, reflecting the impact of
      modern imaging techniques, the application of diverse investigative
      methodologies, and the accessibility of the community to health care. METHODS:
      Material from patients < 18 years of age was collated from the Manitoba Cancer
      Foundation Tumor Registry, the personal records of Winnipeg pediatric
      neurologists, and autopsy data. Patient data were also obtained from hospital
      charts and operating room log books. Histological sections were examined and
      classified according to the American Cancer Society by a single neuropathologist.
      The chi-square test was used for statistical evaluation. RESULTS: During the
      seven-year study period, the diagnosis of brain tumor was made in 89 pediatric
      patients, of which 88 were diagnosed premortem. The overall average annual
      incidence rate for both sexes was 4.03/100,000 child-years, higher than that
      previously reported. The male and female average annual incidence rates were 4.2
      and 3.7/100,000 child-years, respectively. Tumor type and location were
      relatively unremarkable, with an expected peak of medulloblastoma occurring in
      young males. The yearly incidence of tumor occurrence was fairly stable, and the
      geographic distribution of cases within Manitoba, homogeneous. CONCLUSION: The
      highest incidence rates of pediatric brain tumors have been recorded in countries
      possessing sophisticated universal health care systems, possibly reflecting their
      efficacy in disease surveillance.

PMID- 8738925
TI  - Pre-radiation chemotherapy for malignant glioma in adults.
AB  - PURPOSE: To review our experience with pre-radiation chemotherapy for malignant
      glioma. METHODS: Consecutive adults with newly diagnosed glioblastoma, anaplastic
      astrocytoma, anaplastic oligodendroglioma and anaplastic mixed glioma with a
      Karnofsky Performance Score of 60 or greater were treated with one cycle of
      procarbazine, lomustine and vincristine or lomustine alone, prior to radiation.
      Computed tomographic scans were obtained soon after surgery, eight weeks later,
      after radiation, and at regular intervals thereafter. The effects of chemotherapy
      and subsequent radiation and durations of tumor control and survival were
      assessed in this single arm, single center, prospective trial. RESULTS: Thirty
      seven patients started chemotherapy, 36 were rescanned eight weeks after
      diagnosis. Five patients (16%) responded to the first cycle of chemotherapy,
      three had glioblastoma and two anaplastic oligodendroglioma. Seven (19%)
      progressed during the first cycle, 6 had glioblastoma; with the addition of
      radiation one progressive case responded, three stabilized, and three continued
      to progress. Median times to progression and median durations of survival were 26
      weeks and 60 weeks for the entire group, 24 weeks and 44 weeks for glioblastoma,
      and greater than 104 weeks for anaplastic astrocytoma. CONCLUSIONS: Most patients
      with glioblastoma do not respond to one cycle of nitrosourea-based chemotherapy
      given prior to radiation, but patients with anaplastic oligodendroglioma
      sometimes do. Patients with anaplastic astrocytoma may not respond to one cycle
      of chemotherapy, but often respond to subsequent radiation. Judging by survival
      results, radiation can be delayed eight weeks without appearing to compromise
      patient outcome. IMPLICATIONS: Pre-radiation chemotherapy with newer agents can
      be evaluated more fully in the future knowing that brief delays in radiation are
      unlikely to yield substantially inferior results.

PMID- 8738926
TI  - Add-on gabapentin for refractory seizures in patients with brain tumours.
AB  - BACKGROUND: Seizures associated with intracranial neoplasms are occasionally
      refractory to conventional anti-epileptic drugs. Gabapentin (GBP) is one of
      several novel anti-epileptic drugs effective as an add-on therapy for intractable
      seizures but has not been studied in patients with cerebral tumours. PATIENTS AND
      METHODS: We used GBP in a open-label add-on fashion to treat 14 patients with
      intractable seizures associated with intracranial tumours including four
      glioblastomas, four metastases, three recurrent glioblastomas, and one each of
      anaplastic and low grade astrocytoma and meningioma. GBP was added if
      optimization of pre-existing therapy failed and was titrated until seizures were
      controlled. RESULTS: One patient experienced adverse drowsiness. Follow-up ranged
      from 3-24 weeks during which time 7 patients died from disease progression.
      Concurrent therapy included dexamethasone in eight, cranial irradiation in four,
      and radiosurgery in one. Responder rate (number with at least 50% fewer seizures)
      was 100% and persisted throughout follow-up. Complete resolution of seizures
      occurred in 8/14 patients. CONCLUSIONS: GBP was well tolerated in patients with
      brain tumours. Seizure frequency was reduced in all patients and efficacy
      persisted over time; however, the mechanism of this improvement is unclear.
      Concurrent therapy, regression of frequency to the mean, and the lack of controls
      may account for apparent benefit. In addition, because GBP may interact with a
      leucine-related neuronal binding site we also speculate that this novel mechanism
      of action may have been enhanced in our patients due to the abnormal blood-brain
      barrier associated with cerebral tumours. Further investigation and a controlled
      trial are warranted.

PMID- 8738927
TI  - Intracranial chondroma. Report of two cases and review of the literature.
AB  - INTRODUCTION: Chondromas are rare intracranial tumors. The authors present two
      cases of intracranial intradural chondroma, one originating from the falx cerebri
      and the other from the dura mater of the convexity. METHOD AND RESULTS:
      Diagnostic procedures, including magnetic resonance imaging, and surgical
      findings are described. In both cases, pre-operative diagnosis could have been at
      least suspected, and the tumor was completely removed, without recurrence after a
      follow-up of many years. The pathogenesis and pathological findings are
      discussed, and cases from the literature are reviewed. CONCLUSION: Benign
      intradural chondroma has a good prognosis, with no recurrence after surgical
      excision in most cases.

PMID- 8738928
TI  - Paraneoplastic limbic encephalitis in Hodgkin's disease.
AB  - BACKGROUND: Oat cell carcinoma of the lung is the most common cause of
      paraneoplastic limbic encephalitis. Association with other malignancies, in
      particular Hodgkin's disease, is very rare. CASE REPORT: This 23-year-old male
      presented with a six month history of progressive alteration in mental status,
      which consisted of insomnia, short-term memory loss, depression and cognitive
      impairment. Gadolinium MRI of the head showed intense bilateral contrast
      enhancement affecting the medial aspects of the temporal lobes in the region of
      the amygdala and hippocampus. The brain biopsy showed minimal neuronal loss with
      intense perivascular lymphocytic cuffing and microglial nodules. Polymerase chain
      reaction for herpes simplex and cytomegalovirus were negative. With prednisone
      treatment, the patient's neurologic status stabilized but did not improve. Four
      months later, he presented with left axillary lymphadenopathy. Lymph node biopsy
      was diagnostic of Hodgkin's disease. During the chemotherapy, his lymphadenopathy
      subsided and his neurologic and mental status improved. When seen last after
      completion of his chemotherapy, one year after presentation, he had resumed
      normal social activities and was enrolled in a university language course.
      CONCLUSION: This is the first reported case in the English literature of a biopsy
      proven paraneoplastic limbic encephalitis associated with Hodgkin's disease.
      Hodgkin's disease should be thought of as a possible cause of paraneoplastic
      limbic encephalitis in the appropriate clinical setting.

PMID- 8738929
TI  - Addison's disease presenting with cerebral edema.
AB  - BACKGROUND: Increased intracranial pressure with encephalopathy has rarely been
      reported in Addison's disease. METHOD: Case Study. RESULTS: A 16-year-old female
      who presented with cerebral edema of unknown etiology was eventually diagnosed as
      having Addison's disease. She had early morning headaches, fatiguability,
      diarrhea and deterioration in school performance. She was hyponatremic with a
      serum sodium of 128 mmol/L and hyperkalemic with a serum potassium of 5.9 mmol/L.
      She had a low serum osmolality (264 mosm), high urine osmolality (533 mosm) and
      high urine sodium (87 mosm). She had a postural drop in blood pressure and
      diffuse hyperpigmentation. An ACTH stimulation test revealed a low baseline
      cortisol and no response to ACTH. Plasma renin activity was increased. Serum ACTH
      was elevated. She responded well to intravenous fluids and solu-cortef and was
      discharged on hydrocortisone and florinef. She remains well 18 months after the
      acute episode with no neurologic complaints or findings. CONCLUSION: Addison's
      Disease should be considered in the differential diagnosis of symptomatic
      cerebral edema and idiopathic intracranial hypertension.

PMID- 8738930
TI  - Bilateral hypoglossal nerve injury with occipital condylar fracture.
AB  - BACKGROUND: A 20-year-old woman with a right occipital condylar fracture and
      bilateral hypoglossal nerve injury is presented. Only 17 cases of condylar
      fracture have been reported in the literature. METHODS: The patient was evaluated
      with plain films, coronal and axial cut CT, and MRI. RESULTS: MRI showed a
      severely distorted but otherwise normal medulla and a displaced condylar bone
      fragment. CONCLUSION: Condylar fracture may cause twelfth nerve palsy by injuring
      the central or peripheral nerve.

PMID- 8738931
TI  - Re: Long-term treatment of intractable reflex sympathetic dystrophy with
      intrathecal morphine.

PMID- 8738932
TI  - Re: Environmental exposures in elderly Canadians with Parkinson's disease.

PMID- 8738933
TI  - Interaction of a wasp ovarian protein and polydnavirus in host immune
      suppression.
AB  - During parasitization of Heliothis virescens, Campoletis sonorensis deposits an
      egg along with venom, polydnavirus particles (CsPDV), and ovarian proteins (OPs).
      Oviposited eggs are not encapsulated, while washed eggs are encapsulated rapidly
      by H. virescens. Early protection from encapsulation is afforded by a group of 29
      36 kD OP glycoforms. These glycoforms are endocytosed by host hemocytes within 30
      min post-parasitization (pp) and disrupt hemocyte spreading behavior and egg
      encapsulation through at least 24 h p.i. Purified CsPDV does not protect eggs
      from encapsulation early, but disrupts hemocyte spreading and egg encapsulation
      from 24 h through at least 5 days p.i. Functional activity of CsPDV appears to be
      correlated with time-dependent accumulation of virus-specific proteins in
      parasitized insects. We propose that the fast-acting 29-36 kD OP protects
      Campoletis eggs from encapsulation until accumulation of CsPDV proteins which
      sustain immunosuppression.

PMID- 8738934
TI  - Phagocytosis of latex beads by Biomphalaria glabrata hemocytes is modulated in a
      strain-specific manner by adsorbed plasma components.
AB  - Circulating phagocytes of the mollusc Biomphalaria glabrata help determine the
      fate of invading Schistosoma mansoni larvae. In mediating cytotoxicity against
      this trematode parasite, phagocytic hemocytes may interact with unidentified
      plasma components. In this study, positively and negatively charged latex beads
      were coated with plasma for use in in vitro phagocytosis assays. Hemocytes from
      S. mansoni-susceptible and -resistant strains of B. glabrata were tested for
      their ability to internalize beads coated with homologous and heterologous plasma
      components. Electrophoretic analysis showed that differences in the plasma
      polypeptides adsorbed to latex beads were charge-related, but no consistent
      strain-specific differences were detected. Hemocytes from a susceptible strain
      phagocytosed negatively charged latex pretreated in plasma form a resistant
      strain of snail at a higher rate than beads treated in plasma from the
      susceptible strain. Pretreatment of susceptible hemocytes with resistant plasma
      reduced subsequent phagocytosis of beads coated with resistant plasma, consistent
      with blocking of receptors on the susceptible hemocytes with resistant strain
      plasma components. Exogenous lectins detected no differences in the carbohydrates
      on beads coated with plasma from either snail strain. However, strain differences
      in endogenous lectins are suggested by differential binding of neoglycoproteins
      to plasma coated beads. The plasma component(s) responsible for the differential
      phagocytosis of beads treated in the two plasma strains by hemocytes from the
      susceptible strain of B. glabrata remain(s) to be identified.

PMID- 8738935
TI  - An invertebrate (Molluscan) plasma protein that binds to vertebrate
      immunoglobulins and its potential for yielding false-positives in antibody-based
      detection systems.
AB  - Commercial immunoassay kits that incorporate monoclonal antibodies are being used
      increasingly to screen tissues and plasma from invertebrates for the presence of
      antigens that are taken to be homologues of the vertebrate immunogen. We report
      the presence of a protein (BgL115r) in the plasma of Biomphalaria glabrata that
      binds to immunoglobulins from a variety of vertebrates. BgL115r (ca. 230 kD non
      reduced, ca. 115 kD reduced on SDS-PAGE) binds to the F(ab')2-region of murine
      IgG. Binding could be inhibited with high concentrations of N-acetyl-D
      glucosamine (GlcNAc). BgL115r was found to yield false positive signals in an
      ELISA based assay.

PMID- 8738936
TI  - Sympathetic innervation of the amphibian spleen: developmental studies in Xenopus
      laevis.
AB  - Spleens from larval and adult South African clawed frogs (Xenopus laevis) were
      examined using sucrose-potassium phosphate-glyoxylic acid (SPG) histofluorescence
      for norepinephrine. Innervation of the larval Xenopus spleen is barely detectable
      at stage 54 and gradually increases during prometamorphosis (stage 57/58) until
      metamorphic climax (stage 66). This development of innervation late in the larval
      life of the animal was highly sensitive to environmental conditions and to
      rapidity at which development occurred. Prevention of overt metamorphosis by
      sodium perchlorate blockade prevented the development of noradrenergic (NA)
      splenic innervation in some, but not all, tadpoles examined. Depletion of T
      lymphocytes by early larval thymectomy did not alter the kinetics or pattern of
      splenic NA innervation.

PMID- 8738937
TI  - A bursal stromal derived cytokine induces proliferation of MHC class II bearing
      cells.
AB  - To delineate the mechanisms of early embryonic chicken bursapoiesis, we developed
      several virally transformed stromal cell lines. Extensive phenotyping of one of
      these lines, BSL.2, with a panel of mAb mapped it as deriving from the E11 bursal
      surface epithelium. The functional properties of BSL.2 were assessed in vitro by
      culture of its conditioned medium with either embryonic bursal cells (BC) or
      adherent cell depleted bone marrow (BM). In both these populations there was an
      induction of proliferation during the first 72 h of culture, followed by a
      subsequent loss of proliferative activity coincident with the appearance of
      phagocytic and non-specific esterase positive adherent cells, which remained
      viable in culture for up to 3 weeks. Flow cytometric analysis of the
      proliferating cells demonstrated an increase in the number of MHC Class II+ (B
      L+) cells for both BM and BC. There was, however, an overall decrease in total
      viable cell number during the period of proliferation, demonstrating the
      stimulation of a specific subpopulation of cells. FACS separation of the
      unstimulated adherent depleted BM and BC populations demonstrated that only a
      subpopulation of the B-L+ cells proliferated in response to BSL.2 CM in addition
      to a subpopulation of B-L-BM. BSL.2 CM stimulated B-L+ BM and BC co-expressed the
      antigen detected by 68.1, which has been described as a M[symbol: see text]
      marker, but is also detectable on bursal lymphocytes. In ovo administration, at
      E11, of concentrated BSL.2 conditioned medium resulted in a significant increase,
      by E18, of bursal weight and Bu-1 and B-L+ cell number. There were no
      simultaneous alterations to the spleen. Preliminary MW analysis of the BSL.2
      supernatant has revealed an active factor of approximately 90 kDa.

PMID- 8738938
TI  - Stimulation via the CD43 coreceptor augments T cell proliferation during the
      early phase of antigen-induced activation.
AB  - R2/60 is a monoclonal antibody (mAb) that recognizes the murine CD43 molecule
      expressed on mature T cells, developing thymocytes, and a subset of bone marrow
      hematopoietic stem cells. Recent studies using R2/60 demonstrate that CD43 is a
      costimulatory receptor involved in the activation of murine T cells. In the
      present study we have examined the kinetics of CD43-mediated costimulation in
      murine T cell populations including purified CD4+ and CD8+ peripheral T cells,
      and T cells activated in antigen-induced mixed-lymphocyte cultures. In each
      population, CD43 stimulation significantly enhanced T cell proliferation compared
      to non-CD43 activated cultures. CD43 costimulation was greatest in conjunction
      with suboptimal CD3 stimulation, and was most efficient during the early phase of
      antigen-driven activation, suggesting that under normal biologic conditions the
      role of CD43 may be to augment T cell responses early in immune activation.

PMID- 8738939
TI  - Functional magnetic resonance imaging in clinical neurology.
AB  - Functional magnetic resonance imaging is a relatively new, noninvasive technique
      which has a maximum spatial resolution in the range of 1 mm and temporal
      resolution of 0.1-1 s. The technique is not quantitative but results have proved
      reliable and reproducible and studies are quick to perform. Already substantial
      progress has been made in mapping the visual, sensorimotor and auditory systems
      and promising results achieved in the study of higher cognitive function such as
      memory and linguistic processing. Clinical applications have been made in
      epilepsy surgery, the study of schizophrenia, genetic abnormality and cerebral
      injury.

PMID- 8738940
TI  - Cognitive impairment in asymptomatic stages of HIV infection. A longitudinal
      study.
AB  - Seventy-eight asymptomatic HIV-seropositive (aHIV) subjects were examined by
      means of an extensive neuropsychological test battery in comparison with 32 HIV
      seronegative controls. They were also tested with regard to CD4+ and serum p24
      antigen. Fifty-six of them completed a clinical follow-up of 12 up to 36 months
      and 35 also underwent a second session of neuropsychological, CD4+ and p24
      antigen assessments at a 12- to 18-month interval from the first session. Results
      obtained lead to the following conclusions: (a) even among aHIV subjects there is
      a significant prevalence (28.2%) of cognitive abnormalities for which no cause
      other than HIV can be found, and therefore this suggests the possible development
      of HIV-related brain damage since the earliest stages of infection; (b) most
      sensitive to early HIV-related cognitive impairment are timed psychomotor tasks
      and memory tasks which require attention, learning and 'active' monitoring or
      retrieval of information; (c) during the early asymptomatic stages of HIV
      infection, there is no clear-cut evidence of a cross-sectional relationship
      between cognition and immunological/ virological markers (at least in the high
      ranges of CD4+ cell counts considered here); only in relatively more advanced
      stages does this relationship become evident in the subgroup of aHIV subjects
      with cognitive abnormalities; (d) the presence of cognitive abnormalities in
      early HIV infection is predictive of a further decrease in cognitive functioning
      and faster progression to AIDS-this latter reflected by a faster rate of decline
      in the number of CD4+ cells and by an increase in positivity of serum p24
      antigen.

PMID- 8738941
TI  - A clinical profile of corticobasal degeneration presenting as primary progressive
      aphasia.
AB  - We report a patient with primary progressive aphasia who first presented with
      amnesic aphasia that developed over the course of 3 years into nonfluent aphasia
      with buccofacial apraxia, followed in the next year by cognitive impairment and
      parkinsonism. Pathological findings were typical for corticobasal degeneration
      except for the distribution of cortical atrophy. This case suggests that
      corticobasal degeneration should be included in the differential diagnosis of
      primary progressive aphasia, especially in association with parkinsonism.

PMID- 8738942
TI  - Low-grade non-Hodgkin B-cell lymphoma presenting as sensory neuropathy.
AB  - Low-grade non-Hodgkin B-cell lymphoma was found during the evaluation of 3 aged
      patients with predominantly sensory neuropathy of mild to moderate severity.
      Presenting manifestations were sensory ataxia and right ulnar mononeuropathy in a
      75-year-old man, and painful dysesthesias of the legs in two 78-year-old women. A
      neurophysiological study showed mainly axonopathic alterations. M-protein was
      present in all cases (Ig-kappa in two, triclonal gammopathy
      IgG(kappa)/IgM(kappa)/IgM-gamma in one). The male patient had IgM antisulfatide
      antibody in high titer, whereas the other 2 patients had cryoglobulinemia (type
      II and type III, respectively). Our report emphasizes the occurrence of mild
      polyneuropathy as presenting manifestation of low-grade non-Hodgkin lymphoma,
      different from the clinicopathological entity of neurolymphomatosis, in which
      severe nerve damage occurs in association with manifest lymphoma, related to
      nerve infiltration by lymphomatous cells. Alternative pathogenetic mechanisms,
      such as antibody-mediated nerve damage, or vasa nervorum changes caused by
      cryoglobulin, may be implicated in our cases. Non-Hodgkin lymphoma should be
      considered in the diagnostic evaluation of polyneuropathy of unknown cause,
      especially in patients with paraproteinemia and/or cryoglobulinemia.

PMID- 8738943
TI  - Myoglobinuria due to quail poisoning.
AB  - Quail poisoning is known to produce an acute myoglobinuric syndrome. The cause of
      this syndrome is still unknown. It has been suggested that a toxic effect or a
      genetic sensitivity plays a major role. Ten patients with a history of quail
      poisoning were examined to determine their present state and the course of the
      disease. A muscle biopsy was performed in 2 of these patients who complained of
      muscle cramps after exercise. The activities of several glycolytic mitochondrial
      and lipolytic enzymes were estimated. In all 10 patients the physical
      examination, electromyogram findings and conduction velocities were normal. Serum
      levels of CK, aldolase and lactic acid were also within normal range. In the 2
      patients with cramps, all enzyme activities were normal in muscle tissue. Our
      findings possibly exclude a preexisting enzyme defect as a cause of myoglobinuria
      in quail poisoning. Considering that 4 of our patients continued the consumption
      of quails without further problems, we suggest that the major factor contributing
      to quail poisoning must be toxic.

PMID- 8738944
TI  - Felbamate as add-on therapy.
AB  - Felbamate is a novel anti-epileptic drug (AED) which has recently been associated
      with reports of aplastic anaemia and liver failure. We have conducted an open
      label add-on assessment of the tolerability and efficacy of this compound in 111
      adult patients with refractory epilepsy attending a tertiary referral centre. The
      mean follow-up period was 4 months (range 1-8 months). Sixty-three (57%) were
      ongoing, 38 (34%) had discontinued felbamate and a further 10 (9%) were
      withdrawing. Reasons for discontinuing felbamate were adverse events in 23 (21%),
      increase in seizures in 11 (10%) and lack of efficacy in 14 (12%). Behavioural
      disturbances occurred in 14 patients, being the most likely adverse event to
      result in discontinuation. No cases of aplastic anaemia or liver failure were
      observed in this group. Felbamate appears to be a broad-spectrum AED. Seven
      percent of the patients had more than 95% seizure reduction (2 patients were
      seizure free), whilst a further 13% had significant improvement ( > 50% reduction
      in seizure frequency). In conclusion, felbamate seems to be an effective AED. In
      view of its association with potentially life-threatening complications, its use
      should however be restricted to patients with medically refractory epilepsy.

PMID- 8738945
TI  - Investigations on the point mutations at nt 5460 of the mtDNA in different
      neurodegenerative and neuromuscular diseases.
AB  - Point mutations of the mitochondrial genome are often considered to be the cause
      of certain neurodegenerative disorders and mitochondrial myopathies. Recently,
      there has been a report on Alzheimer's disease (AD) point mutations at position
      5460 of the mitochondrial genome located within the ND2 gene. Using allele
      specific PCR with a sensitivity of detection of less than 1% mutated mtDNA, we
      investigated postmortem brain samples from 48 patients with AD and blood samples
      of 15 patients with clinically diagnosed AD. In addition, we investigated tissue
      samples of patients with different neuromuscular disorders and patients with
      Downs syndrome. Independent of the tissue analysed very few of all the tested
      samples of patients showed a point mutation at nt 5460 with a base substitution
      from G to A. Two out of 19 brain and 48 blood samples from controls carried this
      mutation. The G to T transversion was not found in any of the so far tested
      samples. Our results do not support the previously reported significant high
      frequency of these mutations in AD.A polymorphism seems more likely.

PMID- 8738946
TI  - Implicit memory in parkinsonian patients: evidence for deficient skill learning.
AB  - The aim of this study was to investigate procedural learning in idiopathic
      Parkinson's disease (PD) patients. For this purpose, 18 nondemented PD patients
      and 20 age-matched healthy subjects were trained to learn a visuoperceptual skill
      (mirror reading) and a cognitive skill with a motor demand (puzzle assembly
      task). In 3-day sessions, the patients were requested to perform with repeated
      and unrepeated stimuli, in order to distinguish between pure procedural learning
      and skill learning at least partially supported by explicit memory retrieval. In
      the mirror reading task, the PD patients showed normal improvement in reading
      times for repeated words but no improvement at all for unrepeated stimuli. In the
      puzzle assembly task, PD patients did not show any significant learning either
      for repeated or unrepeated stimuli. These results, which document deficient
      learning of procedures in parkinsonians, are discussed in the light of
      conflicting data reported regarding implicit memory in PD.

PMID- 8738947
TI  - Chlamydia pneumoniae associated with central nervous system infections.
AB  - We identified 15 patients with serological evidence of current Chlamydia
      pneumoniae infection when we studied 263 patients with central nervous system
      infections among an adult population of 3 million in 1993. In 9 of the 15
      patients no other associated or etiological agents were found. One patient died.
      Sequelae appeared in 7 patients. In neurological infections, C. pneumoniae may be
      more prevalent as an associated agent than appreciated, and adequate antibiotic
      therapy may be life-saving.

PMID- 8738948
TI  - Bromocriptine therapy in early-stage Parkinson's disease.
AB  - We evaluated bromocriptine monotherapy during the early stage of Parkinson's
      disease (Hoehn and Yahr stage I or II). Of the 120 patients registered as
      participants in this trial, 96 were studied. The follow-up period was 48 weeks.
      For the first 24 weeks they were all placed on bromocriptine with or without
      anticholinergic drugs; for the second 24 weeks, 75 of them were still kept on the
      same medication, with 21 requiring additional levodopa. Clinically, the former
      group showed a good response to the bromocriptine monotherapy, while the latter
      responded poorly to it (requiring in addition levodopa). We think that
      Parkinson's disease encompasses a heterogeneous group of patients of whom about
      75% are well treated by bromocriptine alone at the early stages of the illness.

PMID- 8738949
TI  - Mollaret's meningitis: a new aetiologic feature.

PMID- 8738950
TI  - Raymond syndrome: a validation.

PMID- 8738951
TI  - Changes in migraine symptoms from childhood to adolescence.

PMID- 8738952
TI  - Recurrent meningitis and encephalitis associated with herpes simplex type 2:
      demonstration by polymerase chain reaction.

PMID- 8738953
TI  - Intention tremor exaggerated by visually guided movement.

PMID- 8738954
TI  - Evolution of pontine and extrapontine myelinolysis: clinical correlation with
      serial CT and MRI studies.

PMID- 8738955
TI  - Molecular aspects and the pathological basis of primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) has been considered to be a 'model auto-immune
      disease' for more than two decades. However, the underlying pathophysiology of
      PBC and the relationship with the associated serological abnormalities have been
      hitherto elusive. Beginning in 1987 with the cloning and subsequent
      identification of the mitochondrial autoantigens of PBC, progress has come
      rapidly and we can now sketch several potential pathogenic pathways through which
      disease occurs. More than 90% of patients with PBC produce autoantibodies to
      mitochondria, and the antoantigens involved have been identified as related
      components of the 2-oxo-acid dehydrogenase complexes (OADC), including the E2
      subunits of the pyruvate dehydrogenase complex (PDC-E2), the branched chain 2-oxo
      acid dehdrogenase complex and 2-oxo-glutarate dehydrogenase complex, Protein X
      and E1 alpha. The cDNAs of each of the E2 subunits of OADC have been cloned and
      characterized. Moreover, the epitopes of the antimitochondrial antibodies (AMA)
      have been mapped at the highly conserved lipoyl domain E2 subunits. The use of
      recombinant peptides produced by these clones has greatly facilitated the
      detection of AMA. In addition, nucleotide sequence analysis of PDC-E2 specific
      human monoclonals and combinatorial Fabs strongly suggests that these
      autoantibodies are derived from clonal selection of a restricted set of
      somatically mutated immunoglobulin germline genes. Most interestingly, however,
      the use of monoclonal reagents to PDC-E2 has demonstrated that there is an
      increased expression of either PDC-E2, or a cross-reactive molecule, on the
      luminal surface of biliary epithelial cells in patients with PBC. These data
      provide a scenario to explain the tissue specific pathology associated with PBC
      and several interesting underlying pathophysiological mechanisms.

PMID- 8738956
TI  - Analysis of the initiation period of spontaneous autoimmune thyroiditis (SAT) in
      obese strain (OS) of chickens.
AB  - The early, predictable, onset of spontaneous autoimmune thyroiditis (SAT) in
      Obese strain (OS) chickens provides a unique opportunity to analyse the
      mechanisms initiating autoimmunity which is virtually impossible to obtain in
      humans. In this study we focused on the respective roles of viruses and
      macrophages in the initiation of SAT. To analyse viruses, leukosis virus-free OS
      chickens were bred over three generations and reared under gnotobiotic
      conditions. By 2 weeks of age there were no differences in the levels of thyroid
      mononuclear cell infiltration between these and control animals. The role of
      mononuclear phagocytes in SAT was determined by their depletion via injecting
      newborn OS chicks with silica or carrageenan and dichloro-methylene diphosphonate
      encapsulated into liposomes. Although this treatment did not substantially change
      the amount of macrophages in primary lymphoid organs or blood, there was
      destruction of splenic architecture and, most importantly, mononuclear cell
      infiltration of the thyroids was significantly lower compared to controls. The
      role of activated macrophages in SAT is discussed.

PMID- 8738957
TI  - Murine genotype influences the specificity, magnitude and persistence of murine
      mercury-induced autoimmunity.
AB  - Genetic factors are major contributors in determining the susceptibility to
      systemic autoimmune diseases. We studied the influence of genotype on systemic
      autoimmunity by treating female mice of the H-2s strains SJL/N, SJL/J, A.SW, and
      B10.S with mercuric chloride (HgCl2) for 10 weeks and then following autoantibody
      and tissue immune deposits during the subsequent 12 months. All strains developed
      antinucleolar antibodies (ANoA) of the IgG class which reacted in immunoblotting
      with a 34-kDa nucleolar protein identified as fibrillarin. The titre of ANoA
      attained after 10 weeks' treatment varied from 1:1,280 to 1:20,480 in the order:
      A.SW > SJL > > B10.S. Following cessation of HgCl2 treatment ANoA and
      antifibrillarin antibodies (AFA) persisted for up to 12 months, although some
      B10.S mice showed pronounced reduction not only of their autoantibody titres, but
      also systemic immune deposits when compared to other H-2s strains. A second set
      of autoantibodies targeted chromatin and in some mice specifically histones, and
      were distinguished from the ANoA by a rapid decline after treatment and a
      susceptibility linked to the non-H-2 genes of the SJL. Tissue levels of mercury
      remained elevated above untreated controls throughout the study period,
      suggesting that the mercury detected in lymphoid tissues may provide stimulation
      of lymphoid cells specific for fibrillarin for a considerable period after
      exposure has ceased. We conclude that H-2 as well as non-H-2 genetic factors
      distinctly influence not only the susceptibility to induction of autoimmunity,
      but also the specificity and magnitude of the response.

PMID- 8738958
TI  - Transgenic expression of interleukin 10 in the pancreas renders resistant mice
      susceptible to low dose streptozotocin-induced diabetes.
AB  - Transgenic mice expressing interleukin 10 (IL-10) within the beta cells of the
      pancreas were used to assess the role of this cytokine in the development of
      diabetes following low-dose streptozotocin treatment. Nontransgenic mice injected
      with low doses of streptozotocin were largely resistant to the induction of
      hyperglycaemia; that is, average blood glucose values, although above mean blood
      glucose levels of buffer-injected controls, did not exceed 14 mmol/l. In sharp
      contrast, IL-10 transgenic mice exhibited significant sensitivity to the
      diabetogenic actions of streptozotocin resulting in a mean blood glucose level of
      21.6 mmol/l at the end of the 56-day study period. Histological analysis of
      pancreata from streptozotocin-injected transgenic mice revealed severe insulitis
      and destruction of pancreatic beta cells, whereas their streptozotocin-injected
      nontransgenic littermates remained completely insulitis-free. According to
      immunocytochemical analysis, the pancreatic inflammatory infiltrates of
      streptozotocin-injected transgenic mice contained CD4+ and CD8+ T lymphocytes, B
      lymphocytes and macrophages. Furthermore, various adhesion molecules, the co
      stimulatory molecule B7-1 and the Ia antigen could be detected. Splenocytes from
      streptozotocin-injected transgenic mice did not transfer disease to irradiated
      syngeneic nontransgenic recipients, suggesting that the presence of IL-10 in
      streptozotocin-injected mice had a general immunostimulatory effect but did not
      lead to the activation of beta cell-specific T cells. Our data suggest a critical
      role for IL-10 in the development of diabetes in vivo despite its established
      immunosuppressive activities in vitro.

PMID- 8738960
TI  - Apoptosis of T cells and macrophages in the central nervous system of intact and
      adrenalectomized Lewis rats during experimental allergic encephalomyelitis.
AB  - The adrenocortical response is central to recovery from experimental allergic
      encephalomyelitis (EAE) in the Lewis rat, as reflected by the increased severity
      of the disease in adrenalectomized animals. The protection conferred by
      glucocorticoids is related to the immunosuppressive effects of the steroid, which
      may include apoptosis of immunocompetent cells. Here we describe T-cell
      infiltration and apoptosis in spinal cord lesions of intact (INT) and
      adrenalectomized (ADX) rats during the course of EAE. The normal disease course
      (peak clinical score 3) was induced following intra-peritoneal transfer of 4 x
      10(7) myelin basic protein (MBP)-sensitized spleen lymphocytes to INT rats.
      Maximum apoptosis of infiltrating T cells (32%) was evident on day 7 and was
      associated with the expected increase in circulating corticosterone levels and
      the onset of disease remission. ADX rats, which have no corticosterone response,
      administered 4 x 10(7) cells displayed rapid and fatal EAE with only minimal
      signs of T-cell apoptosis (1.9-3.8%). In order to delay the onset and prolong the
      disease in ADX rats, a lower cell dose was used. In ADX rats injected with 1 x
      10(6) cells, disease onset was comparable to INT 4 x 10(7) rats but disease
      progression was equally rapid and T-cell apoptosis (1.4-8.5%) was similarly low
      to that seen in ADX rats given the higher dose of cells. Transfer of the lower
      number of splenocytes (1 x 10(6) cells) to INT rats resulted in only mild EAE
      (clinical score 0.5-1) which was reflected both in low T cell apoptosis (1.7-16%)
      and circulating corticosterone levels. In all treatment groups very few apoptotic
      macrophages were detected ( < 1% of all macrophages) and no differences between
      groups were apparent. The results suggest that glucocorticoid-mediated T-cell
      apoptosis, whether initiated directly or indirectly, may contribute to the
      recovery phase of EAE in Lewis rats.

PMID- 8738959
TI  - NOD mouse diabetes: the ubiquitous mouse hsp60 is a beta-cell target antigen of
      autoimmune T cells.
AB  - In the NOD mouse, the onset of beta-cell destruction is associated with
      spontaneous development of T-lymphocytes reactive to members of the 60 kDa heat
      shock protein (hsp60) family, including the Mycobacterial (MT) and the human (H)
      hsp60 molecules. Diabetes in the NOD mouse is a spontaneous tissue-specific
      autoimmune disease occurring without prior immunization. Therefore, it has been
      suggested that the anti-hsp60 T cells involved in the autoimmune diabetes of NOD
      mice might reflect molecular mimicry between MT-hsp60 and a beta-cell tissue
      specific molecule sharing similar T cell epitopes, the p277 peptide of hsp60 in
      particular. We cloned and expressed the mouse hsp60 cDNA from a beta-cell tumour.
      This mouse beta-cell hsp60 cDNA was found to be identical in sequence to the
      hsp60 of mouse fibroblasts. We further report that NOD spleen cells and an NOD
      diabetogenic T cell clone C9 responded to the recombinant mouse hsp60 and to its
      peptide M-p277 to the same extent as to H-hsp60 and H-p277. Splenocytes of mice
      of other strains did not respond to p277. Moreover, treatment of 3 month old NOD
      mice with the non-modified self M-p277 peptide was as efficient as H-p277, from
      which it differs in one amino acid, in halting progression of the disease. Thus,
      anti-H-p277 T cells modulating diabetes in the NOD mouse are autoreactive, and
      are targeted at the mouse beta-cell hsp60, which is not tissue specific. These
      findings raise the question of how a non-tissue specific molecule may be a target
      of a tissue-specific autoimmune disease.

PMID- 8738961
TI  - Human muscle acetylcholine receptor alpha-subunit gene (CHRNA1) association with
      autoimmune myasthenia gravis in black, mixed-ancestry and Caucasian subjects.
AB  - We have sought associations with the muscle acetylcholine receptor alpha-subunit
      gene (CHRNA1) in autoimmune myasthenia gravis (MG) patients from three ethnic
      groups; Caucasians and South Africans of Black and Mixed-Ancestry. We found a
      significant association with the HB*15 CA repeat allele in unrelated Black
      myasthenics (n = 18; RR = 2.85; pX2 = 0.04) compared with 52 ethnically matched
      controls. A family-based association study and linkage analysis in Caucasian
      simplex and multiplex families supported a positive association at this locus
      with the longer alleles, including HB*14 to *18. However, no significant
      cosegregation of the disease with the HB alleles could be demonstrated in
      affected sib pairs. Our results suggest that the CHRNA1 locus harbours a minor
      susceptibility gene for developing MG, though we cannot rule out linkage
      disequilibrium with another major gene locus on chromosome 2.

PMID- 8738962
TI  - Anti-Fc gamma receptor autoantibodies from patients with Sjogren's syndrome do
      not react with native receptor on human polymorphonuclear leukocytes.
AB  - Sera from patients with primary Sjogren's syndrome (pSS) have been examined for
      the presence of cell-free Fc-gamma receptor (Fc gamma R) IIIb, which is expressed
      in polymorphonuclear leukocytes (PMN), and the production of related
      autoantibody. Sera from 66 patients with pSS were evaluated by an ELISA using
      recombinant human Fc gamma RIIIb as the substrate and by flow cytometry. Cell
      free Fc gamma RIIIb was also detected by an ELISA. The fine specificity of
      autoantibodies was established by inhibition with a preparation of Fc gamma RI
      plus Fc gamma RII, and two ELISAs using Fc gamma RI and Fc gamma RII as the
      substrates respectively. Anti-Fc gamma RIIIb activity was found in 30 patients
      (45%), but 25 of them did not react with autologous PMN, whereas they bound to Fc
      gamma RIIIb eluted from the same PMN in ELISA and Western blotting.
      Autoantibodies from one serum recognized the three receptors, six with Fc gamma
      RII in addition to Fc gamma RIII, and three sera were specific for the latter
      receptor. None of these reacted with Fc gamma RI- and Fc gamma RII-carrying
      cells. Cell-free Fc gamma RIIIb, but negligible amounts of Fc gamma RIIIa, were
      detectable in the patient sera. The membrane expression of CD15, an early
      activation marker, was diminished, while that of three PMN late activation
      markers was markedly enhanced. Taken together, these results suggest that
      autoantibodies are produced following the shedding of Fc gamma RIIIb upon PMN
      activation. A credible candidate for this activation is IgG-containing immune
      complexes.

PMID- 8738963
TI  - Analysis of function, specificity and T cell receptor expression of cloned
      mucosal T cell lines in Crohn's disease.
AB  - Monoclonal populations of mucosal T cells were established from the earliest
      visible lesions in eight patients with well defined Crohn's disease. The FACS
      phenotype of all the mucosal derived clones to date are TCR alpha/beta+, CD3+,
      CD4+, and CD45RO+ memory cells. TCR variable region Beta chain analysis revealed
      predominantly V beta families 1, 2, 5.1, 5.2, 6, 7 and 8, with V beta family
      analysis supporting antigen expansion in the diseased mucosa. Putative
      autoreactivity was evaluated by stimulating individual clones with a battery of
      antigens and determining proliferation and IL-2 production by thymidine
      incorporation at 72 h. Antigens tested included crude Crohn's diseased (CD) colon
      and small bowel homogenates, CD brush border preparations, crude CD colon and
      small bowel mucin, and purified CD small bowel mucin. Controls included clone,
      APC, tetanus toxoid and either PHA or Staphylococcus enterotoxin B. A total of
      200 clones were studied with 29.5% or 59 clones demonstrating proliferation
      and/or IL-2 production. T cell receptor V beta gene usage evaluated in a small
      number of reactive clones correlated with the expanded patient families. Seven of
      the fifteen represented families revealed diverse T cell receptor gene use and no
      disease overlap.

PMID- 8738964
TI  - Genetics of systemic autoimmunity.
AB  - Despite enormous efforts, the pathogenesis of lupus and other autoimmune diseases
      remains unresolved, but recent studies in lupus mice have contributed several
      major advances that provide new impetus to this research. Among these is the
      identification of the Fas/FasL apoptosis gene defects in the lymphoaccumulation
      manifesting lpr and gld mutant lupus mice. Although the specific Fas/FasL defects
      are confined to lpr/gld phenotypes and to some rare cases of human systemic
      autoimmunity, this and other findings suggest that abnormal apoptotic mechanisms
      may have broad underlying importance in lupus aetiology. Another important
      development has been the identification of predisposing loci in New Zealand lupus
      mice through genome-wide searches with microsatellite-based maps. The findings
      suggest that the genetics of murine lupus follow a multiplicative epistatic model
      of inheritance wherein specific combinations of genes additively contribute to
      phenotype expression. Further studies in these directions will eventually lead to
      identification of the specific predisposing genes that lead to broad T- and B
      cell tolerance defects in this disease.

PMID- 8738965
TI  - T cell-mediated maintenance of natural self-tolerance: its breakdown as a
      possible cause of various autoimmune diseases.
AB  - This paper shows that elimination of a small subpopulation of peripheral T cells
      can elicit activation/expansion of self-reactive T cells from the remaining T
      cells and produce a wide spectrum of organ-specific and systemic autoimmune
      diseases in normal mice; reconstitution of the eliminated T-cell population
      prevents autoimmune development. This regulatory T-cell population expresses the
      CD25 molecule, apparently includes 'activated' T cells, and suppresses immune
      responses to non-self as well as self antigens in an antigen-nonspecific manner.
      Although the degree of abnormality in the T-cell regulation significantly
      influences the spectrum, incidence, and severity of autoimmune disease, the T
      cell abnormality itself cannot determine the specificities of the elicited
      autoimmune responses since a comparable degree of abnormality causes different
      autoimmune diseases depending on the mouse strains used. Host genetic elements
      thus significantly contribute to determining the specificities. These findings
      taken together indicate that one aspect of natural self-tolerance is maintained
      by a T cell-mediated or -dependent control of potentially pathogenic self
      reactive T cells in the periphery, and that defective control, caused by
      environmental insults or genetic abnormalities, suffices to activate self
      reactive T cells, eliciting various autoimmune diseases depending on the genetic
      makeup of the host.

PMID- 8738966
TI  - Th2 and Th1 autoreactive anti-class II cell lines in the rat suppress or induce
      autoimmunity.
AB  - It is now currently thought that Th1 autoreactive cells may induce organ specific
      autoimmune disease and in these situations Th2 cells are considered as regulatory
      cells. However, in other situations Th2 cells may be pathogenic. Thus, some
      chemicals (HgCl2, gold salts or D-penicillamine) may induce Th2-mediated systemic
      autoimmune disorders in susceptible Brown-Norway (BN) rats. In contrast, HgCl2
      induces non antigen specific immunosuppression in Lewis (LEW) rats and protects
      this strain against organ-specific autoimmune diseases such as experimental
      autoimmune encephalomyelitis (EAE). Anti-self MHC class II T cells have been
      detected in both susceptible and resistant strains upon exposure with these
      chemicals. Autoreactive T cell lines that recognize self MHC class II molecules
      have been derived from gold salt-injected BN rats (BNAu lines) and from HgCl2
      injected LEW rats (LEWHg lines). BNAu T cell lines produced IL-4 and transferred
      antibody-mediated autoimmunity in BN rats deprived of CD8+ cells. In contrast,
      HgCl2 protects susceptible rats from Th1-mediated autoimmunity, (autoimmune
      uveoretinitis). LEWHg lines produced IL-2, IFN-gamma and TGF-beta and were able
      to protect LEW rats against cell-mediated autoimmunity (EAE) and (LEW x BN)F1
      hybrids from antibody-mediated, HgCl2-induced autoimmunity. Several points will
      be discussed: the specificity of these autoreactive T cells, the mechanisms by
      which chemicals may induce these cells and the mechanisms by which the immune
      system maintains or reestablishes self tolerance in rats exposed to these agents.

PMID- 8738967
TI  - Antigen processing and T cell repertoires as crucial aleatory features in
      induction of autoimmunity.
AB  - Induction of self-reactive T cell responses leading eventually to autoimmune
      pathology involves several key events: (1) availability of a determinant cross
      reactive with the pathogenic self or foreign determinant upon processing of
      native antigen; the foreign molecule bearing the related determinant may have
      additional processing sites flanking the determinant, or at least different ones
      (the same determinant may only be available on the native self molecule under
      inflammatory conditions) (2) a T cell bearing T cell receptor (TCR) capable of
      response to the autoantigen; (3) ability of the processed self determinant to
      bind efficiently to the appropriate major histocompatibility complex (MHC)
      molecule as well as to interact with the appropriate TCR, coordinated with the
      absence of competitively dominant determinants; and (4) the lack of regulation.
      At any step of this cascade of interactions, the conditions could either favour
      induction of an autoreactive T cell response or the process may be
      truncated/stalled at any step without any adverse effect. A major component
      determining the outcome of the above interactions is the aleatory nature of the
      antigen processing events. Experiments highlighting these aleatory events are the
      focus of this report.

PMID- 8738968
TI  - Common infections, idiotypic dysregulation, autoantibody spread and induction of
      autoimmune diseases.
AB  - A new theory to explain the pathogenesis of autoimmune diseases is proposed. It
      is based on the idiotypic network and does not replace other existing theories of
      autoimmunity. It sets out to explain the emergence of some autoimmune conditions
      in which the proposed autoantigen is non-immunogenic or is not identified at all.
      The theory is based on a series of experiments in which several experimental
      autoimmune diseases were induced in naive mice following active immunization with
      pathogenic idiotypes of autoantibodies. Following immunization with Ab1 (Id) and
      production of Ab2 (anti-Id), the mice developed Ab3 (anti-anti-Id) having the
      original autoantibody characteristics and were associated with the respective
      serological and clinical manifestations of the disease. The human counterpart
      entails infection with common pathogen. Among the anti-pathogen antibodies
      generated, some carry idiotypes of autoantibodies. In healthy subjects with no
      risk factors for autoimmunity (e.g. complement or IgA def, males, normal Ts) the
      idiotypic cascade ends with Ab2 (anti-Id). In subjects prone to autoimmune, Ab3
      (e.g. autoantibodies) develop and may be associated with respective clinical
      manifestations.

PMID- 8738969
TI  - The role of the thymus in the control of autoimmunity.
AB  - Self tolerance among T cells is believed to be maintained by two principal
      mechanisms: clonal deletion for self antigens expressed in the thymus and T cell
      anergy or T cell indifference for those whose expression is solely extrathymic.
      These mechanisms are passive in that they depend on autoreactive T cells being
      either eliminated during their maturation or rendered intrinsically non
      responsive after they have matured. The data presented in this paper indicate
      that this scheme requires modification. First, it is evident that self antigens
      that are commonly regarded as being tissue-specific may also be expressed in the
      thymus where they influence the developing T cell repertoire. Second, it appears
      that there is some T cell-mediated regulatory mechanism that actively prevents
      potentially autoreactive T cells from expressing their disease-inducing
      potential. Our data indicate that this regulatory mechanism is established
      intrathymically and is an innate property of the naive T cell repertoire. The
      mechanism is discussed in terms of what is currently known of the ways that an
      individual T cell responds when interacting with agonist and antagonist peptides
      and possible therapeutic implications are considered.

PMID- 8738970
TI  - Do naturally occurring autoantibodies participate in the constitution of the
      pathological B-cell repertoire in systemic lupus erythematosus?
AB  - Systemic lupus erythematosus (SLE) is the prototype of systemic autoimmune
      diseases. In both human and mouse SLE diseases, the autoimmune response targets a
      restricted set of autoantigens. Many of them are nucleic acids and proteins
      involved in the synthesis and processing of DNA or RNA, a characteristic which
      should be taken into consideration to elucidate the origins of non organ-specific
      autoantibodies. Several observations, in particular those obtained from
      experimental models of SLE induced in normal mice, suggest that the breakdown of
      B-cell tolerance occurs in the periphery. Herewith, we present data further
      supporting the proposition that SLE-associated autoantibodies originate from
      natural autoantibody-secreting B cells activated in the internal environment of
      lupus mice. Thus, one may hypothesize that certain clones of the expanded primary
      B-cell repertoire are selected to differentiate into harmful IgG autoantibody
      secreting clones, thereby raising the question of the nature of immunogenic
      structures involved in SLE. Our analysis of the immunochemical and structural
      properties of anti-nucleosome and anti-myeoloperoxidase monoclonal antibodies
      derived from (NZB x NZW)F1 mice leads us to propose that complexes formed by the
      association of DNA and DNA-binding proteins and, more generally, by anionic
      molecules associated with proteins, possess a selective advantage over other
      autoantigens to induce the differentiation of certain B-cell clones and the very
      special profile of the SLE-autoimmune response. These DNA/DNA-protein complexes
      could also play a role in the activation of the T-cell compartment in SLE.

PMID- 8738971
TI  - Can receptor editing play an important role in normal B-cell development?
AB  - B-cells bearing in-frame light chain rearrangements often continue to
      rearrangement light chain genes, in apparent contradiction to the rules of
      allelic exclusion. The potential role of B-cell receptor self-reactivity in this
      process is discussed in the context of the possible efficiency of rescue of the
      autoreactive cells and the observed high frequency of peripheral B-cells that
      rearrange only a single light chain locus.

PMID- 8738972
TI  - Immune regulation in type 1 diabetes.
AB  - The non-obese diabetic (NOD) mouse is an animal model of insulin-dependent
      diabetes mellitus (IDDM) that shows many of the characteristics of human IDDM. In
      the NOD model, there exists a discrepancy between the onset of insulitis and
      diabetes suggesting the potential existence of some form of immune regulation
      that delays beta cell destruction. Our transfer system using NOD-scid/scid (NOD
      scid) mice as recipients of donor NOD cells suggested that immune regulatory
      cells exist in the periphery of NOD mice, not in the islets. These regulatory
      cells are considered to be memory CD4+ cells which show a Th2 (or Th zero) type
      cytokine profile following activation in vitro. The function of the memory CD4+
      cells seems to change from protective to pathogenic as the disease progresses.
      Moreover, cytokine profiles of this CD4+ CD45RBlow (memory) population shifted
      from a Th2 (or Th zero) to a Th1 type response coincident with the onset of
      hyperglycaemia. These data suggest that the progression of NOD disease from
      insulitis to frank hyperglycaemia is under the control of CD4+ CD45RBlow immune
      'regulatory' cells.

PMID- 8738973
TI  - Programmed cell death in the pathogenesis of murine IDDM: resistance to apoptosis
      induced in lymphocytes by cyclophosphamide.
AB  - The non-obese diabetic (NOD) mouse displays several immune related defects, each
      of which could potentially contribute to the immunopathogenesis of diabetes that
      spontaneously develops in these mice. The reported resistance of NOD-lymphocytes
      to several apoptosis-inducing signals constitutes one such factor. Apoptosis
      plays a key role in the homeostasis of the immune system, as a means of selecting
      lymphocyte repertoires both in primary lymphoid organs and in the periphery;
      distortions in the apoptotic machinery may therefore be hypothesized to be
      implicated in the pathogenesis of autoimmune disorders. We now report that
      cyclophosphamide constitutes an apoptosis signal to peripheral lymphocytes and we
      provide evidence that NOD B cells as well as both CD4 and CD8 T cells display
      resistance to cyclophosphamide-induced apoptosis. These observations support the
      notion that apoptosis resistance in NOD mice exists at various levels, and
      suggest that the CY-sensitive lymphoid population, believed to play an important
      role in inhibiting the disease in diabetes resistant NOD mice (particularly
      males), may be controlled by mechanisms that are mediated by apoptosis.

PMID- 8738974
TI  - Mouse and man: multiple genes and multiple autoantigens in the aetiology of type
      I DM and related autoimmune disorders.
AB  - Autoimmunity to the pancreatic beta cell appears to be a chronic disorder which
      in some individuals progresses to overt type I diabetes [1]. Studies of offspring
      or siblings of patients with type I diabetes (IDDM) and discordant twins who have
      been followed for over 30 years are shedding new light on the disorder. Recent
      advances in molecular biological techniques have resulted in our ability to
      identify novel autoantigens and rapidly develop sensitive and specific tests to
      detect beta cell autoimmunity. The ability to cost-effectively screen the general
      population for diabetes susceptibility is rapidly becoming a reality. Animal
      models of diabetes such as the non-obese diabetes (NOD) mouse have provided
      insights into both pathogenesis of this disease and potentially into the
      prevention of diabetes as well. We will attempt to use our knowledge gained from
      studies of man and the NOD mouse to illustrate what we know and need to learn in
      order to prevent type I diabetes.

PMID- 8738975
TI  - The paradoxical effects of interleukin 10 in the immunoregulation of autoimmune
      diabetes.
AB  - Insulin-dependent diabetes mellitus (IDDM) is a chronic autoimmune disease and
      spontaneously develops in NOD mice and humans. The role of T helper 1 (Th1) and T
      helper 2 (Th2) cytokines in the immunopathogenesis of disease is not understood.
      IL-10 has presented a particularly paradoxical role. Transgenic (Tg) BALB/c mice
      expressing IL-10 in the pancreas exhibited periinsulitis but not insulitis and
      diabetes. However, backcrossing of these Tg mice with NOD mice accelerated the
      onset of diabetes, indicating a pathogenic role for IL-10 in the pathogenesis of
      autoimmune diabetes since it is able to replace the genetic susceptibility
      information on the NOD genome. Conversely, administration of IL-10 to adult NOD
      delayed the onset of and decreased the incidence of diabetes suggesting a
      potential therapeutic role for IL-10 in autoimmune diabetes. Overall, the
      findings indicated a paradoxical role for IL-10 in the immunoregulation of
      autoimmune diabetes.

PMID- 8738976
TI  - A structural model for TCR recognition of the HLA class II shared epitope
      sequence implicated in susceptibility to rheumatoid arthritis.
AB  - HLA molecules associated with rheumatoid arthritis (RA) contain a discrete
      structural element known as the shared epitope, a set of conserved amino acid
      residues located on the alpha helical portion of the class II beta chain. Each of
      the different HLA molecules associated with RA contain the same shared epitope
      sequence, although they may vary markedly in other regions of the class II
      structure, which also determine peptide-class II interactions. Previous
      mutagenesis studies and structural modelling indicate that key polymorphic amino
      acid side chains within the shared epitope sequence are in locations likely to
      contact the T cell receptor (TCR) during the trimolecular activation reaction
      between the HLA-peptide complex and TCR. We have evaluated the potential
      structural basis for such shared epitope recognition by analysing detailed
      molecular models of the arthritis-associated DRB1*0404 molecule and a T cell
      receptor from T cell clone EM025, specific for HLA-DR4 molecules which carry the
      shared epitope. A likely orientation for the trimolecular complex was deduced in
      which the EM025 alpha chain interacts with the DR alpha chain and the EM025 beta
      chain interacts with the DR beta chain; residues Q70 and R71 within the DR beta
      chain shared epitope region are positioned for hydrogen bond interactions
      directly with Q97 of the TCR beta CDR3 region, D30 of the TCR beta CDR1 region,
      and possibly N51 of the TCR beta CDR2 region, indicating a degree of specific
      selection and interaction which encompasses multiple TCR contacts. These findings
      suggest a structural basis for the genetic associations with the HLA shared
      epitope and the potential contribution of this region to oligoclonal T cell
      selection and expansion in RA.

PMID- 8738977
TI  - The penetration of autoantibodies into cells may induce tolerance to self by
      apoptosis of autoreactive lymphocytes and cause autoimmune disease by
      dysregulation and/or cell damage.
AB  - Autoantibodies to intracellular constituents often occur naturally. This would be
      difficult to understand were they unable to penetrate live cells, as was once
      generally accepted; however, they can and in so doing may alter cell functions,
      cause damage and even kill cells by apoptosis. Different autoantibodies have
      different effects and in this paper, further to our previous report on the
      penetration of anti-DNA, the penetration of anti-RNP, which may be a possible
      cause of apoptosis, is demonstrated. Penetration of lymphocytes by autoantibodies
      may play a role in the causation of autoimmune disease, influencing immune
      regulation and causing cell damage either directly or through nucleosomal DNA
      release as a result of apoptosis. This, in turn, could also further promote
      antigen-driven production of anti-DNA. In addition, by causing apoptosis of
      autoreactive cell clones, natural autoantibodies could influence tolerance during
      development and also later in life, thus, paradoxically, helping prevent
      autoimmune disease.

PMID- 8738978
TI  - Influence and fate of T lymphocytes in autoimmunity.
AB  - Many T cells with autoaggressive potential are deleted in the thymus but some
      escape to the general circulation. They do not damage organs such as the insulin
      producing tissue of the pancreas, unless some or all of the following conditions
      are met: high affinity of the antigen receptor on T cells (TCR) for the target
      self antigen, priming by environmental antigens which mimic the target antigen,
      and some inflammatory reaction in the target site. When the liver expresses the
      antigen, any circulating T cells specific for this are deleted in the liver. This
      suggests that the liver may play a role in preventing autoimmune aggression by T
      cells specific for antigens expressed on liver cells. Recent experimental models
      have been set up to test the possibility that an immunoregulatory T cell may
      exist and exert some type of preventive influence on the autoaggressive potential
      of self-reactive T cells.

PMID- 8738979
TI  - Quantitative approach for detection and characterization of formyl peptide
      receptor in solution using a photoaffinity ligand.
AB  - In this paper we describe an assay method for the rapid detection and
      quantitation of human neutrophil FMLP (N-formyl-methionyl-leucyl-phenylalanine)
      receptor molecules. Although different assay methods are available to detect the
      receptor, none are rapid and at the same time allow quantitative detection of the
      binding affinity of the receptor molecule in solution. In our modified method,
      following a binding reaction using photoaffinity ligand, the amount of labeled
      ligand bound to the receptor is separated from the unbound one, thereby
      determining the binding affinity of the receptor protein. This simple procedure
      not only makes it possible to detect the recombinant FMLP receptor protein very
      rapidly, but also provides quantitative assessment of binding. This technique
      therefore allows a partial characterization (identification, determination of
      size and assessment of binding affinity) of receptor molecule in solution in less
      than 24 hours.

PMID- 8738981
TI  - A c-Jun activation domain peptide and its corresponding phosphopeptide have
      potential to adopt alpha-helical conformation.
AB  - The c-Jun transcription factor contains a transactivation domain that belongs to
      the "acidic" type of transcription activator. To determine the secondary
      structure of the Jun activation domain, we synthesized a peptide corresponding to
      amino acids 61 to 98 of c-Jun. Jun N-terminal kinases are able to phosphorylate
      Ser-63 and Ser-73 in vivo, which dramatically increases the transactivation
      potential of Jun. As this phosphorylation event may influence the secondary
      structure, we synthesized a second peptide containing two phosphoserine groups
      instead of serine in positions 63 and 73. Secondary structure predictions did not
      show potential for the peptides to adopt any stable, dominating conformation.
      Both peptides were purified and analyzed by circular dichroism spectroscopy. The
      peptides appeared to be flexible and essentially unstructured in aqueous
      solution. At acidic pH, we observed a decrease in the negative ellipticity at 202
      nm, suggesting that some ordered structure might be present under these
      conditions. alpha-Helical conformation, as a dominating secondary structure, was
      induced in the presence of trifluoroethanol, and there was no significant
      difference between the unphosphorylated and phosphorylated peptides.

PMID- 8738980
TI  - Induction of antibodies against the Plasmodium falciparum p126 antigen in non
      responder H-2b and partial-responder H-2d mice using synthetic peptides.
AB  - The p126 Plasmodium falciparum antigen is processed into two fragments, p50 and
      p73, the latter one containing the subfragments p47 and p18 when the schizonts
      rupture. An absence of antibody response against the p126 antigen has been
      reported recently in H-2b mice and limited to the p73 processed fragment in H-2d
      mice. Synthetic peptides corresponding to various domains of the molecule have
      been used to immunize mice in order to overcome the absence of an immune
      response. Synthetic peptides corresponding to the N-terminus of p50 or p18 as
      well as to the C-terminus of p47 were unable to induce anti-peptide antibodies
      when injected carrier-free or coupled to ovalbumin. Synthetic peptides
      corresponding to the C-terminus of p18 or composed of 6 or 9 serines were able to
      induce anti-peptide antibodies when injected coupled to a carrier protein.
      However, none of these antibodies was able to recognize the native p126 molecule.
      Various synthetic peptides corresponding to the 6-octapeptide [Nt47 (6 x 8)] or
      the 4-octapeptide [Nt47(4 x 8)] repeat sequence localized at the N-terminus of
      the p47 have also been used to immunize mice. No antibodies were generated using
      a carrier-free [Nt47(6 x 8)-Cys]2 or [Nt47 (4 x 8)-Cys]2 peptide, an octameric
      multiple antigen peptide construct [Nt47(6 x 8)]-MAP or the [Nt47(6 x 8)] coupled
      to one or two palmitic acids. In contrast, [Nt47(6 x 8)]-Cys coupled to either
      tetanus toxoid (TT) or ovalbumin (OVA) and [Nt47(4 x 8)]-Cys coupled to OVA
      induced antibodies against the synthetic peptide and the native p126 molecule in
      both H-2d and H-2b mice. A multiple antigen peptide construct [Nt47(4 x 8)-MSP
      3b]-MAP containing 4 [Nt47(4 x 8)] and 4 [MSP-3b] also induced antibodies against
      the synthetic peptide [Nt47(4 x 8)-Cys]2 and the native p126 molecule in both H
      2d and H-2b mice.

PMID- 8738982
TI  - Peptide destabilization by two adjacent D-amino acids in single-stranded
      amphipathic alpha-helices.
AB  - We recently described the local destabilizing effect of systematic double D-amino
      acid replacements for characterization of amphipathic helices in peptides. The
      objective of this study was to determine the destabilizing effect of two adjacent
      D-amino acids incorporated into the center of a single-stranded amphipathic alpha
      helix by hydrogen exchange and guanidine hydrochloride denaturation studies in
      trifluoroethanol (TFE)/water. Data from guanidine hydrochloride titration
      experiments in the presence of 30% TFE suggest that double D-amino acid
      replacements at the center of the helix destabilize the secondary structure by
      4.5 kJ/mol. While the exchange rate for one backbone proton was found to vary by
      a factor of 10 at the replacement position, the remaining backbone protons are
      not markedly influenced by double D-amino acid replacement. These results confirm
      the hypothesis that the energy of -4.5 kJ/mol per residue is a major contribution
      to the stability of helical peptides in water and in solvent mixtures of
      TFE/water.

PMID- 8738983
TI  - Studies on lactam formation during coupling procedures of N alpha-N omega
      protected arginine derivatives.
AB  - We evaluated the quantity of delta-lactam generated during the synthesis of
      arginine-containing dipeptides using Z-Arg(Tos)-OH, Boc-Arg(Tos)-OH, Fmoc
      Arg(Boc)2-OH and Fmoc-Arg(Pmc)-OH and assayed several carboxyl-activating
      procedures for coupling the protected arginines to different amino components. We
      observed significant amounts of delta-lactam during the synthesis of Z-Arg(Tos)
      methyl ester and Z-Arg(Tos)-amide, as well as of Boc-Arg(Tos)-chloromethyl
      ketone. The mixed anhydride coupling procedure and the di-Boc-protecting
      guanidino group induced more delta-lactam formation than any other coupling or NG
      protection method. The amide, benzyl, 4-(NO2)-benzyl and methyl alpha-carboxyl
      protected amino acids generated more delta-lactam than did those protected by
      tertbutyl or N2H2-Boc. So far it has not been possible to propose a general
      mechanism for delta-lactam formation or a process that completely abolishes it.
      Therefore, this side reaction should be considered almost inevitable. Its
      minimization requires examination of arginine-containing peptides in each
      specific synthesis.

PMID- 8738984
TI  - Synthesis of N alpha-protected aminoacyl 7-amino-4-methyl-coumarin amide by
      phosphorous oxychloride and preparation of specific fluorogenic substrates for
      papain.
AB  - We report an improved procedure for the synthesis of fully protected aminoacyl 7
      amino-4-methylcoumarin amide (MCA) employing the phosphorous oxychloride
      anhydride method. Seven Boc-X-MCA [where X = Arg(NG Tos), Cys(S-Bzl), Thr(O-Bzl),
      Ser(O-Bzl), Phe, Leu and Gly] and Z-Tyr(O-Me) were synthesized using this
      procedure, with yields ranging from 50% to 75%. These aminoacyl-MCA derivatives
      were employed for the synthesis of epsilon-NH2-caproyl-Leu-X-MCA, a fluorescent
      peptide series, which were assayed as papain substrates. All of them were
      completely hydrolyzed by papain, indicating that all of the Boc-X-MCA derivatives
      obtained were practically free of racemization. Since epsilon-NH2-Caproyl-Leu-(S
      Bzl)Cys-MCA is very susceptible to hydrolysis by papain, quite resistant to
      hydrolysis by chymotrypsin and not hydrolyzed by trypsin, it is recommended for
      assays of thiol-proteinases in which specificity is required.

PMID- 8738985
TI  - Interobserver variation in duplex sonographic scanning in the femoropopliteal
      tract.
AB  - The diagnostic value of duplex sonographic scanning was demonstrated in a number
      of studies, but there is lack of consensus on which characteristic of the Doppler
      spectrum correlates best with the severity of peripheral vascular disease. In a
      prospective study we quantified the interobserver variation in duplex scanning
      for the diagnosis of peripheral vascular disease. Forty-one patients with
      intermittent claudication were independently examined by two observers. The
      observers were unaware of the angiographic findings. Reproducibility of
      classification and separate characteristics of the Doppler spectrum were
      expressed as kappa coefficients, Pearson correlation coefficients, and
      repeatability coefficients. PSV was the most reproducible characteristic of the
      Doppler spectrum. The classification of peripheral disease in 0 to 19%, 20 to
      49%, 50 to 99%, and 100% diameter reduction was highly reproducible (kappa 0.68).
      The other characteristics of the Doppler spectrum were moderately to poorly
      reproducible; wave form contour, spectral broadening, and end diastolic velocity
      had kappa values of 0.56, 0.20, and 0.56, respectively. Our findings justify a
      simplification of the criteria for duplex sonographic scanning for diagnosis of
      peripheral vascular disease.

PMID- 8738986
TI  - Sonographic appearance and distribution of normal cervical lymph nodes in a
      Chinese population.
AB  - In 100 normal subjects who had a sonographic examination of the neck, 1211 lymph
      nodes were detected. In all the subjects, at least five lymph nodes were seen.
      The distribution, number, echogenicity, shape, presence or absence of echogenic
      hilus, and the sharpness of nodal borders of normal cervical lymph nodes were
      determined. The usefulness of these sonographic features in understanding the
      normal distribution and characteristics of the nodes in the Chinese population is
      discussed. The relationship between the shape and size of lymph node also was
      assessed.

PMID- 8738987
TI  - Is there a correlation between aortic Doppler velocimetric findings in diabetic
      pregnant women and fetal outcome?
AB  - At present, the role of Doppler velocimetry in monitoring fetal well-being in
      diabetic pregnancies is controversial. The present study was conducted to
      determine if fetal aortic velocity waveforms were correlated with fetal outcome
      in pregnancies complicated by diabetes mellitus. Fetal aortic blood flow was
      prospectively assessed in 30 pregnant women with insulin-dependent diabetes
      mellitus. Systolic-diastolic ratios were obtained at 2 week intervals between 18
      and 38 weeks of gestation. They were analyzed according to several fetal outcome
      variables. Infants with presumed fetal distress during labor and neonates with
      respiratory abnormalities (respiratory distress syndrome, persistent fetal
      circulation, or transient tachypnea of the newborn) showed statistically
      significant elevations of aortic Doppler indices (P < 0.031 and < 0.011,
      respectively). However, these correlations lacked clinical relevance. The infants
      demonstrated no evidence of fetal distress at birth since Apgar scores were > 7
      at 5 min in all but one neonate. No relationship was found between the mean third
      trimester fetal aortic systolic-diastolic ratios and perinatal death, preterm
      deliveries, birth weight, Apgar scores at 1 and 5 min, and neonatal metabolic
      abnormalities. These data demonstrate a poor correlation between fetal aortic
      Doppler waveform analysis and fetal outcome. Therefore, fetal aortic Doppler
      velocimetry cannot be used as a means of assessing impending fetal compromise in
      offspring of diabetic mothers.

PMID- 8738988
TI  - Translabial ultrasonography and placenta previa: does measurement of the os
      placenta distance predict outcome?
AB  - The aim of this study was to assess the value of the measurement of os-placenta
      distance by translabial ultrasonography in the evaluation of placenta previa.
      This method was used in 40 women with suspected placenta previa to measure the
      distance between the placenta and internal cervical os. Sonographic diagnoses
      were compared to placental location determined at delivery. Translabial
      ultrasonography proved superior to the transabdominal route in both diagnosis and
      exclusion of placenta previa. Measurement of the os-placenta distance can be used
      as an adjunct to clinical assessment to predict the likelihood of safe vaginal
      delivery in cases of suspected placenta previa.

PMID- 8738989
TI  - Evaluating blunt abdominal trauma:role for ultrasonography.
AB  - Patients in unstable condition with suspected blunt abdominal trauma require
      rapid evaluation to assess the need for laparotomy. Ultrasonography is fast and
      uses portable equipment, and it can be used in the resuscitation area to detect
      free intraperitoneal fluid as an indication of intraabdominal injury in the
      patient in unstable condition. To determine the utility of emergency abdominal
      sonography for evaluating patients with blunt abdominal trauma, a prospective
      study was designed to compare ultrasonography to diagnostic peritoneal lavage.
      Emergency sonography was performed prior to diagnostic peritoneal lavage on 54
      acutely injured patients in the resuscitation area. Our results reveal that
      ultrasonography has a sensitivity of 87%, a specificity of 100%, and an overall
      accuracy of 96% for detecting free intraperitoneal fluid. We conclude that
      ultrasonography is a reliable method for the emergent evaluation of blunt
      abdominal trauma and can be used in place of diagnostic peritoneal lavage as the
      initial indicator of significant intraperitoneal injury requiring surgical
      intervention.

PMID- 8738990
TI  - Rate-based management of fetal supraventricular tachycardia.
AB  - We reviewed the ultrasonographic studies and the clinical course of 22 fetuses
      with supraventricular tachycardia to determine whether the heart rate alone could
      serve as a basis for conservative management. Hydrops was not encountered with
      heart rates under 230 beats per minute. The conditions of all 22 fetuses
      stabilized without invasive administration of medications. Eighteen were
      delivered vaginally and only four by cesarean section. No fetal or neonatal
      losses occurred. Regardless of the type of supraventricular tachycardia, reducing
      heart rate in these fetuses to levels preventing or resolving hydrops allowed
      term vaginal delivery, thereby reducing the substantial problems of ventilating
      an immature or hydropic neonate.

PMID- 8738991
TI  - Digital tapping of the superficial temporal artery: significance in carotid
      duplex sonography.
AB  - To determine whether tapping on the superficial temporal artery correctly
      identifies the ECA during carotid sonography, prospective evaluation of the
      reflection of the temporal tap on the spectral waveform was recorded and graded
      as 3+, 2+, 1+, or 0 in each ECA, ICA, and CCA, with 3+ being the most brisk
      response in each carotid system (ipsilateral CCA, ICA, and ECA). The pattern of
      response was evaluated in patients with and without hemodynamically significant
      (> than 50% diameter) stenoses in CCA, ICA, and ECA. The most frequent pattern of
      response to tapping on the superficial temporal artery was 3+ in the ECA, 2+ in
      the CCA, and 1+ or 0 in the ICA. This pattern was found in 41% (82/200) of
      systems overall. Whether or not stenoses were present in any branch of the
      extracranial carotid system, the strongest response (3+) was found in the ECA
      (58/200 [87%] with stenosis; 119/200 [89%] without stenosis, and lesser responses
      in the other arteries: 2+ in the CCA 31/200 [46%] with stenosis; 63/200 [47%]
      without stenosis, and 1+ or 0 in the ICA 58/200 [87%] with stenosis and 103/200
      [77%] without stenosis). This pattern was unaltered by the degree of stenosis in
      the ECA or in the ICA. In 92.5% of the systems interrogated, the response was
      greater in the ECA than in the ICA. Tapping on the superficial temporal artery
      may be used as a reliable method of identifying the ipsilateral ECA even in
      instances of significant atherosclerotic disease in the ECA, CCA, or ICA.

PMID- 8738992
TI  - Evaluation of umbilical venous blood flow by Doppler color flow mapping and
      conventional ultrasonographic methods.
AB  - Ultrasonographic measurement of umbilical venous blood flow as a reflection of
      placental blood flow has been used for assessment of fetal well-being. Because
      fetal and maternal factors may prevent satisfactory measurement of umbilical
      venous diameter and flow velocity, an alternative method would be helpful. We
      found that, in 35 human fetuses between 18 and 35 weeks of gestation, that both
      variables for umbilical venous flow calculation can be measured from a single
      Doppler color frame with close measurement agreement to conventional combined
      cross-sectional pulsed Doppler ultrasonographic measurements. Thus, this method
      provides an alternative to the conventional method or may be used for a cross
      check and has the potential for automated flow calculation.

PMID- 8738993
TI  - Combined hypertrophic pyloric stenosis and duodenal web in Down syndrome:
      sonographic and radiographic diagnosis.

PMID- 8738994
TI  - Ultrasonography of primary renal lymphoma in a child.

PMID- 8738995
TI  - Sonographic diagnosis of a ureteral diverticulum.

PMID- 8738996
TI  - Use of laparoscopic ultrasonography to detect ovarian remnants.

PMID- 8738997
TI  - Hyperintense thrombus within the inferior vena cava: sonographic demonstration of
      acute circulatory arrest.

PMID- 8738998
TI  - Sonographic and DNA-based prenatal detection of Gorlin syndrome.

PMID- 8738999
TI  - Service documentation and the biomedical engineer: results of a survey.

PMID- 8739000
TI  - Electromagnetic interference testing of somatosensory and near-infrared devices
      used in the microgravity and hospital environments.

PMID- 8739001
TI  - Membrane-based, dry-reagent prothrombin time tests.
AB  - The authors describe a prototype membrane-based, dry-reagent prothrombin time
      assay for whole blood. This system uses an asymmetric polysulfone membrane to
      separate plasma from red blood cells, and works with samples as small as 10
      microliters. The membrane contains calcium and thromboplastin, and permits the
      reactions of the complete extrinsic pathway to occur with minimal distortion from
      membrane surface interactions. Thrombin generation is monitored optically using a
      rhodamine-110-based fluorescent thrombin substrate. Fluorescence kinetics are
      analyzed to produce a prothrombin-time--equivalent parameter that can be
      converted to an international normalized ratio (INR) value. The system provides
      results that correlate well with conventional liquid phase prothrombin time
      assays (R2 = 0.96).

PMID- 8739002
TI  - Computation of time-specified tolerance intervals for ambulatorily monitored
      blood pressure.
AB  - Hypertension is an important risk factor for strokes, heart attacks, and other
      vascular diseases. Pharmacologic treatment of high blood pressure reduces the
      incidence of these complications and prolongs life, so there is a strong
      incentive to identify and treat individuals with high blood pressure. The
      development of automatic instrumentation for noninvasive and ambulatory blood
      pressure monitoring makes it possible to follow the time course of blood pressure
      variations continuously in healthy peer groups to be used as a reference standard
      as well as in potentially hypertensive subjects. For clinical applications,
      tolerance intervals should be substituted, whenever possible for prediction
      limits. When only hybrid data (time series of data collected from a group of
      subjects) are available, such a tolerance interval can be difficult to determine
      following a parametric approach similar to the procedure used for the computation
      of prediction intervals when consideration of both within-subject and among
      subjects variances is wanted. The authors have developed a nonparametric method
      for the computation of such tolerance intervals. Because the method is based on
      bootstrap techniques, it does not require the assumption of normality or symmetry
      in the data and is thus more appropriate when dealing with small samples. The
      method was used to establish time-qualified reference limits for series of blood
      pressure and heart rate values monitored automatically in healthy individuals of
      both genders. The use of these tolerance intervals may eliminate many false
      positive and false-negative diagnoses that might be obtained when relying on time
      unspecified single samples. These limits can serve as a reference for comparisons
      of a given subject's blood pressure series over time, yielding nonparametric
      measures of extent and timing of any blood pressure excess or deficit. Such
      indices can then be used for an objective and positive definition of health, for
      the screening and diagnosis of disease, and for gauging responses to treatment.

PMID- 8739003
TI  - Computer-based medical system for the computation of blood pressure excess in the
      diagnosis of hypertension.
AB  - A computer-based system for assessing hypertension was designed by combining
      hardware for automatic, long-term blood pressure (BP) measurement with a set of
      software modules for computing time-specified tolerance intervals and evaluating
      measures of BP excess. BP is so variable that the identification and proper
      definition of hypertension are highly ambiguous when based on single
      measurements. One first step in dealing with such variability is to replace the
      constant limits for BP frequently used in the assessment of hypertension by a
      time-specified reference interval. Once such a threshold is available, a
      hyperbaric index can be computed by numerical integration as the total area
      (within one cycle) of any given patient's BP above the threshold. In order to
      examine the extent of normal physiologic excess, a series of 266 systolic and
      diastolic BP and heart rate (HR) measurements were automatically monitored every
      30 minutes for at least 48 hours from clinically healthy subjects, aged 19 to 25
      years. Original data were used to obtain 90% tolerance intervals for each gender
      separately. The hyperbaric index was then computed for each individual BP
      profile. The distribution of the maximum hyperbaric index (maximum of the values
      computed for systolic, mean arterial, and diastolic BP levels shows a highest
      value of 14.839 mmHg x hr for the men and of 10.229 mmHg x hr for the women.
      These values represent a testable threshold for assessing hypertension based on
      the proposed approach. The tolerance intervals obtained from the reference
      population were also used to compute hyperbaric indices for a series of 175 BP
      measurements sampled from clinically healthy people, as well as a series of 60
      measurements sampled from patients with mild hypertension. Sensitivity and
      specificity in the diagnosis of hypertension based on the hyperbaric index were
      both 100%, as opposed to values obtained from computing the BP load, the average
      of the BP series, or the circadian amplitude, all of which provided a much poorer
      diagnostic test. The software system developed for automatically establishing
      time-qualified tolerance limits from a reference population and assessing the
      extent and timing of BP elevation for a test subject may help to establish a
      prognosis and diagnosis, with a correspondingly better assessment of health
      status, to initiate treatment if needed, to time treatment when it is most
      desirable and least harmful in terms of undesired effects, and to gauge the
      patient's response to treatment.

PMID- 8739004
TI  - New standard for medical equipment management programs.
AB  - This article is based on the current draft of a new AAMI equipment management
      standard (AAMI EQ56). Until now, no documentation has clearly specified the
      requirements for an equipment management program. At the time of the writing of
      this article, a February 1996 Committee Draft of the new standard was out for
      ballot and public review. Comments will be reviewed at a meeting of the AAMI
      Patient-Care Equipment Management Committee in June 1996, in conjunction with the
      AAMI Annual Meeting, and the standard could be formalized as early as October
      1996. Readers should keep in mind that, while the final standard may differ
      somewhat from the material presented here, the author of this article and BI&T's
      staff felt that the interest of a very large portion of the AAMI membership
      warranted an advance article describing the content and general direction of the
      document.

PMID- 8739005
TI  - Diagnostic X-ray fundamentals: the tube.

PMID- 8739006
TI  - There's no such thing as "safe equipment".

PMID- 8739007
TI  - Problem-based learning in consultation psychiatry.
AB  - Problem-based learning (PBL) is a method of instruction gaining increased
      attention and implementation in medical education. In PBL there is increased
      emphasis on the development of problem-solving skills, small group dynamics, and
      self-directed methods of education. A weekly PBL conference was started by a
      university consultation psychiatry team. One active consultation service problem
      was identified each week for study. Multiple computerized and library resources
      provided access to additional information for problem solving. After 1 year of
      the PBL conference, an evaluation was performed to determine the effectiveness of
      this approach. We reviewed the content of problems identified, and conducted a
      survey of conference participants. The most common types of problem categories
      identified for the conference were pharmacology of psychiatric and medical drugs
      (28%), mental status effects of medical illnesses (28%), consultation psychiatry
      process issues (20%), and diagnostic issues (13%). Computerized literature
      searches provided significant assistance for some problems and less for other
      problems. The PBL conference was ranked the highest of all the psychiatry
      resident educational formats. PBL appears to be a successful method for assisting
      in patient management and in resident and medical student psychiatry education.

PMID- 8739008
TI  - Effects of psychiatric consultation on medical consumption in medical outpatients
      with low back pain.
AB  - A randomized, controlled, clinical trial (N = 104) was conducted to test the
      hypothesis that a protocol of collaboration and communication between neurologist
      and general practitioner, sustained with psychiatric consultation, would reduce
      medical consumption (especially of diagnostic procedures and medication) in
      medical outpatients with low back pain. The intervention was designed at the
      health care provider level; the psychiatrist did not see or examine the patient.
      A reduction in medical consumption could not be demonstrated. As there was a
      great variation in adherence to the protocol in the experimental group, this
      might explain the lack of hypothesized effects. Full implementation of the
      protocol seemed to imply a lower number of major surgery operations, but this
      effect disappeared after excluding cases with a diagnosed hernia. The
      possibilities for consumption reduction for three post hoc-defined patient
      categories (cases with hernia and chronic and nonchronic cases) and the
      consequences for patient selection and treatment intensity are discussed. It is
      concluded that the target groups should be more narrowly defined, and that a more
      intensive intervention might prove to be more effective.

PMID- 8739009
TI  - Ethical, legal, and psychiatric issues in capacity, competency, and informed
      consent: an annotated bibliography.

PMID- 8739010
TI  - Religious issues in the capacity evaluation.
AB  - The authors explore the difficulties present in the capacity evaluation of
      patients with strong religious beliefs. The article reviews the legal protection
      for treatment refusal on religious grounds as well as psychiatry's approach to
      religion. Clinical cases encountered in an urban hospital are presented to
      highlight how the conflicts among psychiatric, religious, and legal issues can be
      resolved. Suggestions are made for incorporating an exploration of religious
      values into the capacity assessment.

PMID- 8739011
TI  - Acute intoxication and substance abuse among patients presenting to a psychiatric
      emergency service.
AB  - It is common for patients to arrive at the Psychiatric Emergency Service (PES)
      under the influence of a variety of drugs. The purpose of this study was to 1)
      determine what impact there was on the PES of patients who arrive after engaging
      in substance abuse within the 24 hours prior to arrival; and 2) describe some of
      the parameters associated with substance abuse and mental illness in the PES
      setting. Consecutive evaluations done at the PES during the study month were
      reviewed retrospectively utilizing the extensive material collected in the
      screening chart. Of the 294 evaluations, 32.0% (n = 94) were on patients with
      acute intoxication and 17.0% (n = 50) had a primary diagnosis of substance abuse
      or dependence; 49 of 50 presented with active substance abuse. Schizophrenic and
      personality disorder patients presented with significant levels of acute
      intoxication (25.2%, 26/103), whereas substance use rate was quite low for
      patients with affective disorder, adjustment disorder, and other diagnoses.
      Alcohol was the overwhelming drug of choice by all diagnostic groups, making it
      difficult to determine group differences in choice of drug. Both the univariate
      and multivariate studies presented demonstrate that regardless of diagnosis, the
      impact of substance abusing patients is substantial. They present with high
      acuity (usually acutely suicidal), require high levels of behavior management,
      and spend more time in the PES. However, they have much less need for psychiatric
      hospitalization. In contrast, the patients presenting with psychosis also have a
      high rate of behavior management needs, but these patients are very likely to be
      hospitalized. These findings suggest that an important role for the PES is a
      "filter" to triage patients to the appropriate treatment setting and that this
      role is fulfilled when the PES is able to provide sufficient time and resources
      for evaluation and/or stabilization.

PMID- 8739012
TI  - Improved pregnancy rates for obese, infertile women following a group treatment
      program. An open pilot study.
AB  - Thirty-seven women with a mean initial weight of 98.5 +/- 18.7 kg completed a
      group treatment program for obese, infertile women. The program lasted for 24
      weeks and included regular exercise and group discussion of topics such as coping
      with the psychological impact of infertility, developing healthy eating patterns,
      and the effects of obesity on reproductive physiology. There was significant
      weight loss (mean weight loss 6.2 +/- 4.5 kg, p < 0.001) and improvement on
      measures of self-esteem, anxiety, depression, and general health. Twenty-nine
      women became pregnant during the follow-up period (21-36 months). Two women were
      avoiding pregnancy, so only six who had completed the group program and wished to
      become pregnant had not conceived by the end of the follow-up period. A further
      five women did not complete the program as they became pregnant while attending
      the group. Our results suggest that active measures to improve mood and self
      esteem, along with better nutrition and weight reduction through diet and
      exercise, can produce considerable improvement in the outcome of treatment for
      infertility in obese women.

PMID- 8739013
TI  - Corticosteroid-induced delirium and dependency.
AB  - A case of a patient with chronic lung disease who developed an addiction pattern
      of corticosteroid dependency is described in which steroid-induced delirium also
      developed. The rare phenomenon of corticosteroid dependency is discussed as well
      as the phenomenology and possible mechanisms of steroid-induced delirium.

PMID- 8739015
TI  - Who is responsible for clinical pharmacology?

PMID- 8739014
TI  - Physostigmine temporarily and dramatically reversing acute mania.

PMID- 8739016
TI  - Teaching healthcare professionals about drug-induced disease: an innovative
      clinical therapeutic approach.
AB  - An innovative conference on the general principles of recognition and management
      of drug-induced disease was developed for healthcare professionals (particularly
      primary care). The full-day conference used a clinical therapeutic approach and
      was a cooperative effort of the United States Food and Drug Administration (FDA)
      Center for Drug Evaluation and Research (CDER) Staff College and Georgetown
      University Medical Center (GUMC). Linked with the FDA MedWatch postmarketing
      surveillance initiative, the conference used multiple formats, including didactic
      presentations, panel discussions, and case discussions led by faculty from
      various disciplines (e.g., internal and family medicine, psychiatry, clinical
      pharmacology, dentistry, clinical pharmacy, nursing, epidemiology). Conference
      topics included new drug approval, pharmacokinetic/pharmacodynamic
      considerations, and clinical assessment of adverse drug events. Tests were
      administered to participants before and after the conference, and participants
      completed a conference evaluation. Mean scores for the pre- and posttests were
      compared globally and by professional discipline. Conference evaluations were
      assessed for responses to eight standardized statements and elicited comments.
      After the conference, mean and median test scores were improved both globally and
      by discipline in comparison to protest results, with improvement on almost all
      individual test questions. Comparison of median scores for the pre- and posttests
      showed small differences between physicians and pharmacists. Evaluations showed
      markedly positive response to standardized statements, including enhancement of
      professional growth; elicited comments were supportive of conference
      effectiveness and attendee acceptance. This conference, which utilized a
      combination of educational formats, was designed to present material of an
      innovative nature. Results indicate that the conference was well-received and
      fulfilled specified learning objectives, including recognition of populations
      particularly vulnerable to adverse drug events and understanding of how
      individual providers can contribute to FDA postmarketing surveillance. Continuing
      educational efforts using this approach are encouraged.

PMID- 8739017
TI  - Acetaminophen toxicity in children: diagnostic confirmation using a specific
      antigenic biomarker.
AB  - Chronic acetaminophen (APAP) toxicity poses a difficult diagnostic challenge to
      the clinician. Signs and symptoms are nonspecific and no currently available
      laboratory study can confirm APAP as the causative agent of hepatic injury. In
      this study an antigenic biomarker for APAP toxicity was used to confirm the
      diagnosis of APAP-induced hepatic failure in two children with chronic APAP
      toxicity. APAP that has been metabolized to N-acetyl-benzoquinone imine (NAPQI)
      reacts with cellular proteins to form 3-(cystein-S-yl)-APAP protein adducts (3
      Cys-A). Serum from both patients was submitted for quantitation of 3-Cys-A by a
      competitive inhibition enzyme-linked immunosorbent assay (ELISA). Concentrations
      of 3-Cys-A in the two patients were 1.97 and 2.77 nmol/mg protein, which are
      similar to concentrations found in adults with hepatic injury secondary to an
      overdose of APAP. Individuals with no exposure to APAP have no detectable 3-Cys-A
      in serum. It was concluded that 3-Cys-A is a useful marker of APAP intoxication
      after long-term ingestion of APAP when total dose and time course of ingestion
      are uncertain, and may prove to be a useful clinical and investigative tool in
      the study of APAP intoxication.

PMID- 8739018
TI  - Clinical pharmacology of multiple-dose losartan, an angiotensin II receptor
      antagonist, in patients with essential hypertension.
AB  - The pharmacokinetic and pharmacodynamic alterations of multiple doses of
      losartan, an angiotensin II receptor antagonist, were examined in nine patients
      with essential hypertension. Participants were given placebo once daily for the
      first 7 days (from day -7 to day -1), and then 50 mg of losartan for the next 9
      days (from day 1 to day 9). The 24-hour blood pressure was measured on days -1,
      1, and 7 and blood samples for measurement of losartan and its active metabolite,
      E-3174, were obtained on days 1 and 7. Plasma concentrations of uric acid and
      plasma clearance were determined before and during treatment with losartan, and
      at the end of the study. Pharmacokinetic parameters after the seventh dose,
      including maximum plasma concentration (Cmax) and time to Cmax (tmax) of losartan
      and E-3174, did not differ significantly from those after the first dose. The
      blood pressure lowering effect of losartan, however, was significantly greater
      after the seventh dose than after the first dose. Plasma uric acid decreased and
      its plasma clearance (ClUA) increased significantly during repeated
      administration with losartan. These values returned to pretreatment levels after
      the end of treatment. These results suggest that although the pharmacokinetic
      profiles of losartan and E-3174 do not change during repeated administration, the
      blood pressure lowering effect in hypertensive patients is greater after multiple
      doses than after a single dose.

PMID- 8739019
TI  - Pharmacokinetics of a new thromboxane A2 receptor antagonist, S-1452, and its
      effect on platelet aggregation in healthy volunteers.
AB  - To study the pharmacokinetics of a new thromboxane A2 (TXA2) receptor antagonist,
      S-1452, eight healthy volunteers were given placebo or S-1452 orally on four
      occasions in step-wise increasing doses of 10 mg, 25 mg, and 50 mg separated by 2
      week intervals. Blood samples for measurement of plasma concentrations of the
      drug and of its inhibitory effect on platelet aggregation were obtained for 24
      hours after administration. Bleeding time after administration was measured. S
      1452 was rapidly absorbed, with a peak plasma concentration at 30 minutes after
      administration. Thereafter, the drug was rapidly eliminated (elimination half
      life, 0.4-0.5 hours), and no drug was detected at 6 hours. The inhibitory effect
      of S-1452 on platelet aggregation, which was stimulated by the TXA2 receptor
      agonist U-46619, persisted more than 6 hours after drug administration. Bleeding
      time was slightly prolonged after a single dose of S-1452. These results suggest
      that although S-1452 is rapidly eliminated in plasma, its inhibitory effects on
      platelet aggregation persist for a longer period. Careful observations are needed
      to prevent potential bleeding episodes during repeated treatment with the drug.

PMID- 8739020
TI  - A pharmacodynamic and pharmacokinetic comparison of intravenous quinaprilat and
      oral quinapril.
AB  - Quinaprilat is the active metabolite of quinapril, an orally active angiotensin
      converting enzyme (ACE) inhibitor. The dose-response and duration-of-effect after
      single intravenous doses of quinaprilat and placebo (part A) and after
      administration of oral quinapril solution and intravenous quinaprilat (part B)
      were assessed in a randomized, crossover study of two groups of 12 healthy
      volunteers. Pharmacodynamic effects of quinaprilat and oral quinapril were
      assessed by measurement of blood pressure changes after an infusion of
      angiotensin I (A-I) at a dose previously determined to produce an increase in
      diastolic blood pressure of 25 mmHg under standardized conditions (A-I pressor
      response). A clear dose-response relationship was demonstrated for quinaprilat in
      this pharmacodynamic model, with 0.5 mg as the lowest effective dose. Doses of
      1.0 mg and higher partially suppressed A-I pressor response for at least 6 hours.
      Onset of action was observed within 15 minutes of intravenous administration of
      quinaprilat and was independent of dose, whereas peak effect and duration of
      action appeared to be dose related. Quinaprilat doses of 2.5 mg and 10 mg
      achieved approximately 50% and > 80% inhibition of the A-I pressor response,
      respectively. In part B, these doses of intravenous quinaprilat were compared
      with oral doses of quinapril previously found to produce 50% (2.5 mg) and 90% (10
      mg) inhibition of the A-I pressor response. The magnitude of effect was similar
      after administration of 20 mg quinapril orally and 10 mg quinaprilat
      intravenously. Duration of action was longer, however, after administration of
      intravenous quinaprilat (10 mg) than after oral quinapril (20 mg), due to the
      higher maximum plasma concentration (Cmax) of quinaprilat. Mean area under the
      plasma concentration-time curve extrapolated to infinity (AUC0-infinity) of
      quinaprilat was similar after the 10-mg dose of intravenous quinaprilat and the
      20-mg dose of oral quinapril. Based on the concentrations of quinaprilat observed
      in this study, the absolute bioavailability of quinapril was approximately 50%;
      intravenous quinaprilat should therefore produce a pharmacodynamic response
      similar to that obtained with oral quinapril at approximately half the dose.

PMID- 8739022
TI  - Pharmacokinetics of CGP 36,742, an orally active GABAB antagonist, in humans.
AB  - A study was conducted to evaluate the pharmacokinetics of CGP 36 742 (3
      aminopropyl-n-butyl-phosphinic acid), an orally active gamma-aminobutyric acid B
      (GABAB) antagonist, in humans. Pharmacokinetic results after a single oral (600
      mg) dose included maximum observed concentration (Cmax), 27 mumol/L (95% CI 22.9,
      30.8); time to Cmax (tmax), 3 hours (median); half-life (t1/2), 3.6 hours (95% CI
      3.24, 3.9); renal clearance (ClR), 125 mL/min (95% CI 114, 136); and absolute
      bioavailability (Fabs), 0.44 (95% CI 0.33, 0.47). Administration with food
      decreased the oral systemic availability (Frel) by 30%. The volume of
      distribution (285 L/kg) was in the order of magnitude of extracellular body
      water. The absorbed fraction of the compound was excreted completely and
      unchanged via the kidney, thus renal function would be the limiting factor for
      excretion. The rate of absorption and amount absorbed did not differ
      significantly between elderly and young healthy male volunteers, both after
      single and multiple doses. There was no gender-related difference in
      pharmacokinetics in healthy elderly volunteers. CGP 36 742 showed an excellent
      safety profile: there were no clinically relevant changes in cardiovascular
      variables, body temperature, or blood chemistry. In the placebo-controlled trial,
      adverse experiences were rare and evenly distributed among participants receiving
      placebo and the study drug. In addition, a newly developed high-performance
      liquid chromatography (HPLC) method for measurement of CGP 36 742 concentrations
      in plasma and urine using fluorescence detection is described.

PMID- 8739021
TI  - Effectiveness and safety of low-dose pravastatin and squalene, alone and in
      combination, in elderly patients with hypercholesterolemia.
AB  - A double-blind, placebo-controlled study was conducted to compare the efficacy
      and safety of low-dose (10 mg) prevastatin and squalene (860 mg), either alone or
      in combination therapy, with placebo in the treatment of elderly patients with
      hypercholesterolemia. Ambulatory elderly patients (N = 102) were assigned in
      randomized fashion to receive active treatment or placebo for 20 weeks after a
      single-blind placebo lead-in period of 8 weeks. Total cholesterol and
      triglyceride levels in plasma were at least 250 mg/dL and less than 300 mg/dL,
      respectively. Concentrations of lipids and lipoproteins were measured, and
      clinical laboratory tests included liver function and creatine kinase
      determinations. Pravastatin 10 mg daily was more effective than squalene in
      reducing total cholesterol, low-density lipoprotein (LDL) cholesterol, and
      triglycerides and in increasing levels of high-density lipoprotein (HDL)
      cholesterol. Combination therapy significantly reduced total cholesterol and LDL
      cholesterol and increased HDL cholesterol to a greater extent than either drug
      alone. Adverse events and clinical laboratory abnormalities were generally mild
      and transient in all groups, and all but two patients finished the study. The
      incidence of side effects was low; myopathy did not occur. Coadministration of
      pravastatin and squalene combined the specific effects of the two drugs on
      lipoprotein concentrations. This combination may be useful and more cost
      effective in elderly patients with hypercholesterolemia, who might have a higher
      incidence of side effects when using larger doses of pravastatin alone.

PMID- 8739023
TI  - Pharmacokinetics and safety of a novel, long-acting, prodrug-type potassium
      channel opener, Y-27152, in healthy volunteers.
AB  - The pharmacokinetics and safety of a novel, long-acting, prodrug-type K(+)
      channel opener, Y-27152, were investigated in healthy male volunteers. In the
      first phase, single oral doses of 0.1, 0.25, 0.5, 0.75, and 1.0 mg of Y-27152 (n
      = 3-6 per dose) were given after overnight fasts in a dose-escalating manner. The
      0.75-mg dose was given both after an overnight fast or after food to examine the
      effects of food intake. In the second phase, multiple doses of Y-27152 were taken
      after meals once daily for 7 consecutive days. In part A of this phase, either
      placebo (n = 3) or 0.5 mg of Y-27152 (n = 6) was taken for 7 days, and in part B
      of this phase 0.5-, 0.75-, and 1.0-mg doses were taken in a dose-escalating
      manner for 1,3, and 3 days, respectively (n = 9). In the single-dose study, peak
      concentration (Cmax) and area under the plasma concentration-time curve (AUC) of
      main active metabolite (Y-26763; M1) increased in parallel with dosage. This dose
      linearity was less obvious with Y-27152, which had an AUC approximately 6 to 10
      times less than that of M1. Administration with food at 0.75 mg resulted in a
      small but significant decrease (approximately 10%) in the Cmax and AUC of M1. At
      doses of 0.5 mg or higher, participants experienced headaches and palpitations,
      which were probably due to the vasodilatory effects and did not require
      treatment. Mean diastolic blood pressure significantly decreased and pulse rate
      increased at doses of 0.5 mg or higher compared with predose values. Plasma renin
      activity was significantly elevated 4 hours after the administration of the 0.75-
      and 1.0-mg doses, but showed no significant change at 0.5 mg. In the multiple
      dose study, the time profile of the plasma concentration of M1 approximately
      coincided with the simulation curves worked out using the pharmacokinetic
      parameters obtained in the singledose study. The incidence of headaches tended to
      increase with dose in part B, but drug administration was not discontinued in any
      case. Plasma renin activity again increased 4 hours after administration. In
      phase B of the multiple-dose study, diastolic blood pressure decreased and pulse
      rate increased compared with predose values. Y-27152 was metabolized to M1 and
      well tolerated in healthy volunteers, and its pharmacologic effects were likely
      caused by vasodilation, which could make it an effective antihypertensive agent.

PMID- 8739024
TI  - Pharmacokinetics and pharmacodynamics of multiple-dose terbinafine.
AB  - Data from clinical trials of terbinafine for the treatment of onychomycosis were
      analyzed with the following two objectives: 1) to identify demographic predictors
      of the duration and extent of systemic drug exposure; and 2) to explore whether
      increased systemic exposure or demographic predictors of increased exposure were
      associated with altered safety or efficacy. Demographic predictors of exposure
      were identified by a model-free, nonparametric approach applied to the sparse
      pharmacokinetic data from the onychomycosis studies. Those covariates were then
      incorporated into a multicompartmental nonlinear mixed effects model. Post hoc
      parameter estimates from the nonlinear mixed effects model provided individual
      measures of exposure. Safety scores were derived for adverse events that were
      frequently attributed to drug exposure and for liver function tests. Terbinafine
      was found to have an average terminal half-life (t1/2) of approximately 3 weeks.
      That terminal elimination phase contributed so little to the total exposure,
      however, that average concentrations accumulated only approximately two-fold at
      steady state with once daily dosing. Age and concomitant hypertension were
      predictors of higher plasma concentrations of terbinafine; smokers had lower
      levels than nonsmokers. Although some statistically significant associations
      between adverse events and systemic exposure were found, in all cases the actual
      frequency of the adverse events and systemic exposure were found, in all cases
      the actual frequency of the adverse events was low, and there were no trends in
      severity with respect to exposure. Above-normal levels of gamma-glutamyl
      transferase were associated with exposure, but there was no trend in severity
      with respect to exposure. No other liver function test abnormalities were
      associated with exposure, nor were there any significant associations between
      adverse events or liver function abnormalities and demographic subgroups that
      differed with respect to exposure. Among patients taking the active drug there
      were no significant associations between exposure levels and efficacy, nor were
      there differences in efficacy between demographic subgroups that differed with
      respect to exposure.

PMID- 8739025
TI  - Pharmacokinetics and pharmacodynamics of tepoxalin after single oral dose
      administration to healthy volunteers.
AB  - This study was conducted to examine the pharmacokinetics and pharmacodynamics of
      tepoxalin in healthy volunteers, an antiinflammatory compound that inhibits
      cyclooxygenase and lipoxygenase. Tepoxalin was absorbed after oral administration
      of single doses from 35 to 300 mg, after which it was rapidly converted to an
      acidic metabolite, RWJ 20142, which inhibits cyclooxygenase but not lipoxygenase.
      The areas under the concentration-time curve (AUC) of tepoxalin and RWJ 20142 in
      plasma increased in a dose-dependent fashion. Administration of the lowest dose
      of tepoxalin completely inhibited whole blood cyclooxygenase for the entire
      period of observation. This inhibition correlated closely with that of secretion
      and aggregation induced by collagen of platelets obtained from these subjects.
      Similarly, administration of tepoxalin was associated with significant inhibition
      of lipoxygenase in whole blood. Lipoxygenase was inhibited a maximum of 60% in a
      time-dependent fashion, and the duration of inhibition was dose-dependent. These
      studies demonstrate that tepoxalin inhibits whole blood cyclooxygenase,
      lipoxygenase, and platelet function after oral administration in humans.

PMID- 8739026
TI  - Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of
      quinidine in healthy volunteers.
AB  - A study was conducted to examine the effect of grapefruit juice on the
      disposition of quinidine sulfate and changes of QT intervals after oral
      administration to twelve healthy male volunteers. Participants received two oral
      doses of quinidine sulfate tablets (400 mg) with 240 mL of water or grapefruit
      juice, each separated by a 1-week washout period. Plasma samples for analysis of
      quinidine and its major metabolite, 3-hydroxyquinidine, were collected for a 24
      hour period and analyzed by a high-performance liquid chromatography method. For
      pharmacodynamic data, the electrocardiograms (ECGs) were performed for 12 hours,
      and the recordings were marked for ECG interval at all blood collection time
      periods. There was no significant difference in pharmacokinetic parameters of
      quinidine when administered with grapefruit juice or water, except for time to
      maximum concentration (tmax), which was 1.6 hours after administration with water
      and 3.3 hours after administration with grapefruit juice. Administration with
      grapefruit juice also resulted in a 33% decrease in the area under the
      concentration-time curve (AUC) of 3-hydroxyquinidine compared with water, but did
      not increase the AUC of quinidine or change the ratio of AUC of 3
      hydroxyquinidine to the AUC of quinidine. Pharmacodynamic parameters, including
      changes in the rate-corrected QT (QTc) interval, closely paralleled the
      pharmacokinetic data, in that administration with grapefruit juice led to delayed
      maximal effect on QTc and reduction in maximal effect. Administration with
      grapefruit juice therefore delays the absorption of quinidine and inhibits the
      metabolism of quinidine to 3-hydroxyquinidine.

PMID- 8739027
TI  - Vesnarinone-induced granulocytopenia: incidence in Japan and recommendations for
      safety.
AB  - Vesnarinone (OPC-8212) is a new positive inotropic agent that augments myocardial
      contractility. A recent multi-center randomized trial in the United States
      demonstrated that 60 mg/day of vesnarinone significantly reduced morbidity and
      mortality and improved quality of life in patients with symptomatic chronic heart
      failure. Vesnarinone, however, is also known for its propensity to cause
      granulocytopenia. In search of effective safety measures against this side
      effect, data have been collected in Japan as part of the post-marketing
      surveillance of this drug. This article reviews the results of this post
      marketing surveillance and other works available to date, including an
      illustrative case report, and presents measures that should be taken with regard
      to safety during treatment with vesnarinone. Vesnarinone-induced granulocytopenia
      has appeared in relatively early stages of vesnarinone therapy, and
      characteristically results in a rapid decrease in granulocyte count. Hematologic
      monitoring should be performed at least once a week during the initial 16 weeks
      of vesnarinone therapy. Granulocyte colony-stimulating factor may contribute to
      recovery from severe granulocytopenia, although it should be used carefully
      because of its potential to cause adult respiratory distress syndrome.

PMID- 8739028
TI  - Nucleotide sequence and expression of ribosomal protein S3 mRNA during
      embryogenesis in the Mexican axolotl (Ambystoma mexicanum).
AB  - We have isolated and sequenced a full-length (0.9 kb) cDNA clone of ribosomal
      protein S3 by subtraction hybridization using a single-stranded cDNA library from
      stage 25-27 (tracer) and the mRNA from stage 15-17 (driver) of embryonic Mexican
      axolotl (Ambystoma mexicanum). The axolotl is a unique animal model for studying
      heart development as well as myofibrillogenesis because it carries a mutation in
      gene c. The deduced amino acid sequence of axolotl S3 protein shows about 93.9%
      identity with human S3 protein over a 243 amino acid residue overlap. When
      compared with mouse and Xenopus laevis ribosomal S3 proteins, the axolotl sequenc
      shows 94.3 and 93.9% identity respectively. Interestingly, the axolotl S3
      sequence shows higher identity at the nucleic acid level with human and/or other
      mammals than with Xenopus. The S3 transcript, as determined by RT-PCR, is present
      at stage 2-4 in a lower amount and the onset of transcription is most likely at
      the beginning of gastrulation (10-12). The expression level of S3 transcripts
      reaches a maximum by mid gastrulation (stages 13-14) and then follows a biphasic
      pattern being lower at stages 16-17 with subsequently steady increases until the
      mid tailbud stages (25-27).

PMID- 8739029
TI  - Mitochondrial dysfunction in spontaneous inbred turkey cardiomyopathy.
AB  - Mitochondrial enzyme activities were examined in cardiac tissues of turkeys with
      spontaneous inbred cardiomyopathy. Marked declines in specific enzyme activities
      were noted for respiratory complexes III and V ranging from 65-90% of the control
      values. No significant differences in complexes I, IV and citrate synthase nor in
      mitochondrial DNA copy number were detected. These results suggest that specific
      mitochondrial enzyme defects occur in cardiac tissues during spontaneous inbred
      turkey cardiomyopathy.

PMID- 8739030
TI  - Bone morphogenetic protein-2 is markedly synergistic with tumor necrosis factor
      in stimulating the production of nerve growth factor in fibroblasts.
AB  - A possible interaction between tumor necrosis factor (TNF) and transforming
      growth factor-beta (TGF-beta) superfamily cytokines in stimulating the production
      of nerve growth factor (NGF) in Swiss 3T3 cells was studied. Although TGF-beta 1
      and Activin A stimulated NGF production in Swiss 3T3 cells, they antagonized the
      stimulatory effect of TNF on fibroblast NGF production when used in combination.
      On the contrary, TNF's stimulatory activity on fibroblast NGF production was
      markedly synergized by bone morphogenetic protein-2 (BMP-2); BMP-2 by itself did
      not stimulate NGF production in the cells. These findings suggest that BMP-2, in
      concert with TNF, plays an essential role in regulating the regeneration of
      peripheral nerves following injury with bone fracture through an indirect
      mechanism by which it stimulates NGF production in fibroblasts.

PMID- 8739031
TI  - Protein disulfide isomerase-catalyzed renaturation of ribonuclease A modified by
      S-thiolation with glutathione and cysteine.
AB  - Renaturation of modified ribonuclease A by protein disulfide isomerase was
      studied. The renaturation rate of fully S-thiolated ribonuclease A with
      glutathione, namely, ribonuclease A-glutathione mixed disulfide (RNase-SG)
      containing 8 moles of glutathione per mole of ribonuclease A (RNase-SG8), by
      protein disulfied isomerase (PDI) was more than three times faster than those of
      fully S-thiolated RNase with L-cysteine and scrambled ribonuclease A.
      Renaturation of RNase-SG species containing 7 or less glutathione was slower than
      that of RNase-SG8. These data seems to favor the hypothesis that S-thiolation of
      nascent proteins with glutathione may occur in the folding process during protein
      synthesis. The applicability of the present method consisted of chemical S
      thiolation and PDI-catalyzed renaturation to the in vitro folding of recombinant
      cysteine-containing proteins is discussed.

PMID- 8739032
TI  - mRNA stabilization in continuous flow translation system.
AB  - In contrast with standard in vitro translation systems, where 1 to 2 copies of
      polypeptide per mRNA molecule are produced, the continuous flow cell-free
      translation system is able to synthesize hundreds of polypeptide molecules per
      one mRNA molecule. Our investigations have shown that the poor yield obtained in
      the standard analytical system is due to rapid mRNA decay as opposed feedback
      inhibition by low molecular weight translation by products. In contrast,
      continuous flow system was found to stabilize mRNA for up to two-three days.
      RNAse activity can not be removed from wheat germ extract unless mRNA is added
      and compartmentalization of the translational machinery occurs.

PMID- 8739033
TI  - Effect of heparin and dextran sulfate on the activity of glutathione reductase
      from yeast.
AB  - Glutathione reductase (EC 1.6.4.2) is a pivotal enzyme of the glutathione
      antioxidant system in a cell. The kinetic studies of the interaction of
      glutathione reductase with unfractionated and low molecular weight heparin and
      dextran sulfate can contribute to explanation of polyanions effect on the
      conformation changes of glutathione reductase. The tested polyanions inhibit this
      enzyme and the inhibition effect depends on the ionic strengths and pH value. The
      most potent inhibitor is dextran sulfate (ID50 is 4.1 micrograms/ml, pH = 6.8,
      without NaCl). The ionic strength (> 100 mM) allows the reactivating of GR if the
      concentration of DS is not higher than 80 micrograms/ml. The inhibition effect of
      tested polyanions is caused by electrostatic interactions with enzyme; the
      kinetic analyses indicate that it is a mixed inhibition with respect to oxidized
      glutathione or NADPH.

PMID- 8739034
TI  - Glutathione regulates 3,3',4,4'-tetrachlorobiphenyl induced cytochrome P450
      metabolism: evidence for a cross-talk between the two major detoxication
      pathways.
AB  - The cytochrome P450 and the glutathione systems are two major pathways of
      xenobiotic metabolism. We tested the effect of hepatic glutathione content on
      P450 CYP1A1/2 induction by 3,3',4,4'-tetrachlorobiphenyl in rainbow trout
      (Oncorhynchus mykiss). Hepatic glutathione status of tetrachlorobiphenyl injected
      fish could be successfully manipulated by injecting (i.p.) glutathione or L
      buthionine-[S,R]-sulfoximine to arrest glutathione synthesis. Tetrachlorobiphenyl
      injection resulted in a 17-fold increase in CYP1A catalytic (ethoxyresorufin O
      deethylase [EROD]) activity. This effect was further potentiated by 2.7-fold in
      fish in which hepatic glutathione content was elevated by 3.6-fold. The induction
      of EROD activity by tetrachlorobiphenyl was 7-fold lower in glutathione deficient
      (78%) liver. Hepatic glutathione deficiency also downregulated
      tetrachlorobiphenyl-induced CYP1A gene expression as indicated by lower CYP1A RNA
      levels. Elevated hepatic glutathione did not influence tetrachlorobiphenyl
      induced CYP1A RNA level, but enhanced CYP1A protein expression. These enzyme
      activity, RNA and protein expression data present compelling evidence suggesting
      the involvement of tissue glutathione in the regulation of tetrachlorobiphenyl
      induced cytochrome P450 dependent metabolism.

PMID- 8739035
TI  - Protein kinase C inhibitor, chelerythrine, potentiates the adrenaline-mediated
      aggregation of human platelets through calcium influx.
AB  - The role of protein kinase C (PKC) using its selective inhibitor, chelerythrine,
      in agonist mediated platelet aggregation was studied. Chelerythrine had no effect
      on the aggregation induced by adrenaline, PAF, collagen and ADP at the maximum
      doses of these agonists. However, it potentiated the aggregatory response of low
      doses of adrenaline (0.4-1 microM). Such an effect was blocked by Ca(++)-channel
      blockers, verapamil and diltiazem indicating the likely involvement of Ca++
      influx in the platelet aggregation during the cascade.

PMID- 8739036
TI  - Viral RNA binding properties of human immunodeficiency virus type-2 (HIV-2)
      nucleocapsid protein-derived synthetic peptides.
AB  - The nucleocapsid (NC) protein of HIV-2 (NCp8) contains two Cys-His arrays which
      function as zinc finger motifs (ZFMs). In this study, we analyzed the viral RNA
      binding properties of NCp8-derived synthetic peptides using ultraviolet (UV)
      cross-linking assay. Several synthetic peptides containing ZFM(s) interacted pH
      dependently with in vitro-synthesized HIV-2 RNA. Although the peptides
      corresponding to the 1st and 2nd ZFMs, respectively, failed to interact with the
      viral RNA, the corresponding peptides flanked by basic amino acid clusters
      interacted tightly. Furthermore, basic amino acid residues within a cluster
      adjacent to ZFMs contributed to the RNA-binding of NCp8 more than Cys and His
      residues within the ZFM in vitro. In competitive UV cross-linking assay using non
      specific RNA as a competitor, the peptides corresponding to the 1st and 2nd ZFMs
      flanked by basic amino acid clusters interacted specifically with viral RNA.
      These findings suggest that both ZFM regions of HIV-2 may be concerned with the
      specificity of packaging of genomic viral RNA into the virion.

PMID- 8739037
TI  - Amplified determination of lipoyl groups by lipoamide dehydrogenase in the
      presence of oxidized glutathione.
AB  - Lipoyl group determination by lipoamide dehydrogenase (NADH: lipoamide
      oxidoreductase; EC 1.8.1.4) was examined using lipoyl lysine as a substrate. The
      reaction was monitored by the coupled oxidation of NADH at 340 nm absorbance.
      Dehydrogenase-mediated NADH oxidation was too slow to be used for the
      quantification of lipoyl groups in the concentration range 1 to 10 microM.
      However, when glutathione disulfide (GSSG) was added to the reaction mixture to
      regenerate the oxidized substrate for the enzyme, NADH oxidation was markedly
      enhanced. This GSSG-dependent enhancement of NADH oxidation was strongly
      dependent upon the lipoyl substrate, but was only slightly dependent on the
      amounts of GSSG without the substrate. In the presence of excess GSSG, NADH
      oxidation was linearly correlated to the concentration of lipoyl lysine up to 10
      microM; this assay is suitable for determining micromolar concentrations of the
      lipoyl moiety.

PMID- 8739038
TI  - Scavenging activity of "beta catechin" on reactive oxygen species generated by
      photosensitization of riboflavin.
AB  - "beta CATECHIN", a preparation containing green tea extract, ascorbic acid,
      sunflower seed extract, dunaliella carotene and natural vitamin E, has been
      designed as a model "universal antioxidant" that offers protection via its
      scavenging action on a wide range of free radicals, both water-soluble and fat
      soluble. Reactive oxygen species like singlet oxygen, hydroxyl and superoxide
      radicals, are often generated in biological systems during photosensitized
      oxidation reactions. We report on the simultaneous effect of "beta CATECHIN" on
      active oxygen species generated during the photosensitized oxidation of
      riboflavin using 2,2,6,6-tetramethyl-4-piperidone (TMPD) as a "spin-trapping"
      agent. The intensities of the resulting stable nitroxide radical adduct, 2,2,6,6
      tetramethyl-4-piperidone-1-oxyl (TEMPONE), were detected by electron spin
      resonance (ESR) spectroscopy. Results show simultaneous, nonspecific and complete
      scavenging action of reactive oxygen species generated in our in vitro model
      system by "beta CATECHIN". It is therefore suggested that "beta CATECHIN" could
      offer protection against free radical insult and in preventing cancer and other
      diseases that are mediated by reactive oxygen species.

PMID- 8739039
TI  - Scavenging effects of salvia miltiorrhiza on free radicals and its protection for
      myocardial mitochondrial membranes from ischemia-reperfusion injury.
AB  - Using low temperature electron spin resonance (ESR) technique, we found that
      Salvia miltiorrhiza injection could scavenge the oxygen free radicals generated
      from ischemia-reperfusion injury in the myocardium as effectively as SOD. Using
      ESR spin trapping technique we found that one of its effective components,
      Danshensu, could scavenge superoxide anion free radicals generated from the
      reaction system of xanthine and xanthine oxidase, and that lipid free radicals
      generated from lipid peroxidation of myocardial mitochondrial membranes could be
      scavenged by another effective component, Tanshinone. The membrane fluidity of
      the mitochondria isolated from the ischemia-reperfused hearts was studied with
      the ESR spin labelling technique, and the TBA-method was used to detect the lipid
      peroxidation. It was found that Danshensu could protect the mitochondrial
      membrane from the ischemia-reperfusion injury and lipid peroxidation.

PMID- 8739040
TI  - Biological activities of human tumor necrosis factor-alpha and its novel mutants.
AB  - Biological activities of human tumor necrosis factor-alpha (hTNF-alpha) and its
      mutants were compared. In cytotoxicity assay with L929 cells, one mutant,
      designated as TNF-B, showed 4.5-fold higher activity than TNF examined. In
      receptor binding assay, TNF-B had almost the same affinity for TNF receptors on
      L929 cells as hTNF-alpha. We also found that TNF-B retained the cytotoxicity of
      hTNF-alpha for HEp-2 cells. TNF-B also had two-fold higher affinity than hTNF
      alpha for receptors on HEp-2 cells (only carrying hTNF-R55) and lower affinity
      for receptors on U937 cells (expressing mainly hTNF-R75). These results suggested
      that TNF-B might still interact with the human TNF-R55 receptor, but it might
      largely lose its ability to bind to human TNF-R75. Changes of biological activity
      of TNFs might be due to an altered affinity to the different types of TNF
      receptor on the target cells.

PMID- 8739041
TI  - Changes in tRNA pattern in ethionine-induced rat putative preneoplastic
      hepatocyte nodules.
AB  - As part of a study to explore further the biochemical pathology of chemical
      hepatocarcinogenesis, cytoplasmic tRNA patterns have been studied in ethionine
      induced rat putative preneoplastic nodules in comparison to surrounding non
      nodular liver and control liver. A new h.p.l.c. methodology, able to resolve
      contemporaneously the numerous components in a tRNA population, has been used.
      The results obtained indicate the presence of marked differences in the
      chromatographic profiles of hepatocyte nodules, non-nodular surrounding liver and
      control liver. The differences are both quantitative and qualitative, with some
      chromatographic peaks showing increases and some decreases or absences. Also, new
      peaks are seen reproducibly in the nodules. The data show major changes in the
      tRNA population during hepatocarcinogenesis that might have mechanistic
      implications.

PMID- 8739042
TI  - Calbindin D28K forms a Ca(2+)-dissociable complex with mellitin in vitro.
AB  - Calbindin D28K (CB), a cytosolic calcium binding protein (CBP), forms a
      macromolecular complex with the polypeptide mellitin (ME) the absence of calcium,
      which can be reversibly dissociated by the addition of Ca2+. The molar ratio of
      CB:ME constituted in this complex is 1:4, suggesting that CB interacts with the
      tetrameric form of ME. Like free tetrameric ME, the CB:ME complex does not
      migrate into 15% non-denaturing polyacrylamide electrophoretic gels, although
      both constituents migrate normally after irreversible complex denaturation by
      heating in sodium dodecyl sulphate (SDS). The interaction of these two proteins
      can be distinguished from the association of calmodulin (CM) with ME, which forms
      a reversibly dissociable, equimolar complex in the presence of Ca2+ and a stable
      non-migrating complex (molar ratio = 1:12) in its absence. Thus, CB and CM appear
      to bind ME under different Ca2+ regulatory control, suggesting possible roles for
      CB as a Ca(2+)-dependent regulatory binding protein.

PMID- 8739043
TI  - Prokaryotic homolog of tubulin? Consideration of FtsZ and glyceraldehyde 3
      phosphate dehydrogenase as probable candidates.
AB  - The bacterial FtsZ protein has recently been suggested as a probable prokaryotic
      homolog of the tubulin family of proteins (Cell 80, 1995, 367-370). We have
      compared the sequence similarity of tubulins to FtsZ and another protein
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Both these proteins exhibited
      similar levels of sequence identity to the tubulins, which in a few cases was
      indicated to be significant. We report that incubation of the GAPDH in
      microtubule assembly buffer causes its polymerization into filamentous
      structures. In eukaryotic cells, GAPDH is known to be associated with
      cytoskeletal structures and it binds specifically to both tubulins and
      colchicine. The latter is a distinctive characteristic of the tubulin family of
      proteins. These observations indicate that similar to the FtsZ proteins, GAPDH
      also exhibits a number of intriguing similarities to the tubulins. Whether any of
      these proteins truly represent the prokaryotic homolog of tubulin, however, is
      unclear at present.

PMID- 8739044
TI  - Purification and characterization of a protein phosphatase that dephosphorylates
      pyruvate kinase in an anoxia tolerant animal.
AB  - A protein phosphatase that dephosphorylates pyruvate kinase (PK) in vitro was
      purified and characterized from the foot muscle of the anoxia tolerant gastropod
      mollusc Busycon canaliculatum. Purification involved three steps: negative
      chromatography through Blue Dextran and CM Sephadex, affinity chromatography on
      DEAE Sephadex and gel exclusion chromatography on Sephacryl S-400. Pyruvate
      kinase phosphatase (PK-Pase) activity was monitored by following changes in PK
      I50 values for L-alanine that had previously been linked to changes in the degree
      of PK phosphorylation. The purified PK-Pase gave a single band on SDS
      polyacrylamide gel electrophoresis with a molecular weight of 41 +/- 1 kdaltons.
      Isoelectric focusing analysis showed that the PK-Pase had an isoelectric point of
      4.2 +/- 0.1. Kinetic analysis showed that the enzyme was a Type 2C protein
      phosphatase with a pH optimum of 6.5. Maximal activity required the presence of
      magnesium ions (KM = 7.9 +/- 0.6 microM) although high concentrations of Mg2+
      were inhibitory (I50 = 2.3 +/- 0.4 mM). The protein phosphatase activity was not
      affected by either spermine, cAMP, cGMP, potassium phosphate, tartrate, NaF,
      HgCl2, citrate or concentrations of CaCl2 less than 10 mM. The enzyme could also
      use ATP, ADP, and GTP as substrates.

PMID- 8739045
TI  - Retinoic acid enhances expression of bone morphogenetic protein-2 in human
      adenocarcinoma cell line (HSG-S8).
AB  - Expression of bone morphogenetic protein (BMP)-2 mRNA was stimulated by retinoic
      acid in human adenocarcinoma cell line, HSG-S8, in a dose-dependent manner.
      Northern blot analysis demonstrated that retinoic acid most strongly increased
      the level of BMP-2 mRNA 6 h after the treatment and the stimulatory effect was
      maintained at 48 h. The mature peptides of 16 and 18 kDa molecular masses of BMP
      2 were also increased in the conditioned medium by the treatment of retinoic acid
      on western blotting. The proliferation of HSG-S8 cells was inhibited by retinoic
      acid, however, retinoic acid did not cause morphological change showing cellular
      differentiation. 1 alpha, 25(OH)2D3, like retinoic acid, clearly increased the
      mRNA level of BMP-2, whereas dibuthryl cyclic AMP remarkably diminished it, and
      bromodeoxyuridine had no effect on the expression of BMP-2 mRNA.

PMID- 8739046
TI  - Conformational relaxation and ligand binding to singly reduced human embryonic
      haemoglobins.
AB  - The reaction of the three human embryonic haemoglobins with aquated electrons
      follows a complex set of steps in which a single haem centre undergoes both
      reduction and spin state changes coupled to slower protein relaxation events. In
      the presence of ferrous haem ligands the spin state changes are coupled directly
      to the ligand binding process. The rate constants for the reaction of the single
      reduced haem with O2 are similar to those determined by flash photolysis at high
      pH, whilst CO binding to the beta type haems is more rapid and the alpha haems
      less rapid than the analogous processes observed using photolysis techniques.

PMID- 8739047
TI  - Light- and cytokinin-induced changes in the levels of leucine and tyrosine
      isoaccepting tRNA species and modified nucleotide contents of total tRNA in
      cucumber seedlings.
AB  - We have determined relative levels of chloroplast leucine and tyrosine
      isoaccepting tRNAs and modified nucleotide contents from total tRNAs isolated
      from dark-grown, light-grown, N6-isopentenyladenine (i6A)-treated dark-grown and
      i6A-treated light-grown cucumber seedlings. Significant increases in the relative
      amounts of tRNA(Leu)2 and tRNA(Leu)3 were observed in the i6A-treated dark-grown
      seedlings compared to dark-grown, light-grown and i6A-treated light-grown
      seedlings. On the other hand, i6A-treated light-grown seedlings tRNA(Tyr)1
      increased to 85% of total tRNAs(Tyr) from about 9% in light-grown seedlings and
      tRNA(Tyr)2 decreased to 15% compared with 91% in light-grown seedlings. Analysis
      of modified nucleotide of total tRNAs indicated that pT, pI, pm1A, pm5C, pGm,
      pm1G, pm2G and pm7G contents were significantly higher in the total tRNA of i6A
      treated dark-grown seedlings than those from untreated dark-grown seedlings.
      Illumination of 8-day-old dark-grown seedlings for 12 h increased the contents of
      pT, pI, pGm and pm1G when compared to 8-day-old dark-grown seedlings with
      extended growth for 12 h in dark. On the contrary, i6A had no stimulatory effect
      in the contents of modified nucleotide in the light-grown seedlings.

PMID- 8739048
TI  - Modification of inositol 1,4,5-trisphosphate concentration of human erythrocytes
      under "in vivo" physiological conditions.
AB  - The concentration of inositol 1,4,5-trisphosphate (InsP3) in erythrocytes from
      volunteers has been found to modify following strenuous physical exercise. The
      basal value was almost regained within some 75 min after the completion of the
      effort. The concurrent variations of pH and blood lactate have also been
      evaluated. Our results represent, to our knowledge, the first evidence of in vivo
      induced intraerythrocyte InsP3 modification. They reinforce the idea of the
      participation of its precursor phosphatidylinositol 4,5-bisphosphate (PtdIns4,5
      P2) in red bood cell shape regulation by contributing to the interactions between
      membrane and cytoskeleton components.

PMID- 8739049
TI  - Lack of evidence of oxidative damage in antioxidant-deficient strains of
      Saccharomyces cerevisiae.
AB  - The content of reactive carbonyls and of glutathione-protein mixed disulfides,
      two indices of oxidative stress, were compared in wild-type Saccharomyces
      cerevisiae and in strains deficient in superoxide dismutase and catalase, and of
      decreased glutathione level. Both indices were higher in stationary than in
      logarithmic cultures and were not increased in antioxidant-deficient strains.
      Oxidation of dichlorofluorescin, an estimate of peroxide production, measured in
      the presence of exogenous peroxidase, was higher in antioxidant-deficient
      strains. These results corroborate our previous results on compensatory
      antioxidant mechanisms in the mutant yeast strains.

PMID- 8739050
TI  - The place of cotreatment with growth hormone and human menopausal gonadotropin
      (hMG) in ovarian stimulation.

PMID- 8739052
TI  - Monoamniotic twinning and zona manipulation: a survey of U.S. IVF centers
      correlating zona manipulation procedures and high-risk twinning frequency.
AB  - PURPOSE: An anonymous survey of IVF centers in the United States was employed to
      calculate frequencies of multiple gestation, monozygotic multiple gestation, and
      monoamniotic multiple gestation. Rates for zona-manipulated (ICSI, SUZI, zona
      drilling, mechanical assisted hatching) and non-manipulated pregnancies were
      compared. RESULTS: From 42 IVF centers in the United States, a total of 143
      pregnancies was ascertained from zona-manipulated cycles. A multiple gestation
      frequency of 16.1% was reported. Five monoamniotic twin gestations were
      identified: four from manipulated cycles and one from a nonmanipulated cycle. All
      monoamniotic twin gestations resulted in live births, although three showed
      significant intrauterine growth discordance and one newborn was diagnosed with
      the VATER malformation sequence. CONCLUSIONS: Monoamniotic multiple gestations
      may be increased in zona-manipulated cycles. The potential obstetric risks and
      complications of zona manipulation should be discussed with patients.

PMID- 8739051
TI  - Significance of an abnormal response during pituitary desensitization in an in
      vitro fertilization and embryo transfer program.
AB  - PURPOSE: Our purpose was to evaluate the IVF-ET outcome in patients who did not
      achieve timely pituitary-ovarian suppression following "long"-protocol GnRH
      agonist (GnRH-a) administration. METHODS: A retrospective analysis was done on 96
      IVF treatment cycles characterized by a delayed response (DR) to long-protocol
      GnRH-a treatment. The study included those patients who either achieved ovarian
      suppression (E2 < or = 110 pM) despite an elevated LH level (group DR-A) or had
      pituitary desensitization (LH < or = 1.5 IU/L) without ovarian suppression (group
      DR-B) on day 12 of GnRH-a treatment but needed an extended course of GnRH-a
      treatment to achieve complete suppression. These patients had gonadotropin
      stimulation either from day 12, despite an elevated level of LH (subgroup DR-A1;
      n = 13) or elevated E2 levels (subgroup DR-B1; n = 9), or after achieving a
      complete hypogonadotropic-hypopgonadal state following an extended course of GnRH
      a treatment [subgroups DR-A2 (n = 46) and DR-B2 (n = 28)]. The outcome was
      compared with that of 88 cycles of normal responders (group NR) who had pituitary
      ovarian suppression by day 12 day GnRH-a administration. RESULTS: Ovarian
      response and pregnancy rates in subgroups DR-A1 and DR-A2 were statistically not
      different and comparable to those in the NR group. In subgroups DR-B1 and DR-B2,
      E2 response and rates of oocyte retrieval and pregnancy were significantly lower
      than those in the other groups, but fertilization and cleavage rates were
      similar. The requirement of gonadotropin for ovarian stimulation was
      comparatively higher in subgroup DR-A2 and both DR-B subgroups. CONCLUSIONS:
      There was no treatment cancellation in group NR and both DR-A subgroups, but 22%
      of the cycles in DR-B1 and 14% of the cycles in DR-B2 were canceled due to poor
      ovarian response. It therefore appears that during long-protocol pituitary
      desensitization, the post-GnRH-a level of serum E2, rather than LH, better
      predicts IVF-ET outcome.

PMID- 8739053
TI  - The effects of coculture with autologous cryopreserved endometrial cells on human
      in vitro fertilization and early embryo morphology: a randomized study.
AB  - PURPOSE: The aim of this study was to examine the influence of endometrial cells
      on the fertilization rate and early embryonic morphology following routine in
      vitro fertilization (IVF). Cryopreservation with subsequent thawing allowed the
      use of autologous somatic cells, thus minimizing the risk of transmission of
      infective agents. Interpatient variability was eliminated by randomizing oocytes
      from each cycle into the control or coculture group. RESULTS: Two hundred ninety
      four oocytes from 24 IVF cycles (21 patients) were included in the study (145
      coculture and 149 control). The normal fertilization rate of control oocytes
      (56.4%) was not significantly different from that of oocytes cocultured with
      endometrial cells (61.4%). The mean number of blastomeres in cocultured embryos
      (3.65) was not significantly different from the number in control embryos (3.46)
      2 days after insemination, but the proportion of embryos with minimal or no
      fragmentation was significantly higher in the coculture group [34/84 (40.5%) vs.
      17/80 (21.3%); P < 0.01]. CONCLUSIONS: The inclusion of cryopreserved autologous
      endometrial cells in routine clinical IVF procedures does not influence
      fertilization or the early cleavage rate but may reduce the extent of embryo
      fragmentation during the early cleavage divisions.

PMID- 8739054
TI  - Pituitary response to early follicular-phase minidose gonadotropin releasing
      hormone agonist (GnRHa) therapy: evidence for a second flare.
AB  - PURPOSE: Our purpose was to determine the pituitary response to minidose
      follicular-phase GnRHa and see if a second flare can be achieved. METHOD: A
      prospective, consecutive series of 12 couples with tubal-factor infertility
      underwent 14 cycles of minidose GnRHa. Women were given a 25- or 50-migrograms
      dose of leuprolide acetate (LA) on cycle days 2 and 5. On cycle days 3 and 4 no
      LA was given but 2 ampoules of pure follicle stimulating hormone (FSH) was
      administered. Beginning day 6, a combination of LA and FSH was administered.
      RESULTS: Following a dose of only 25 micrograms of LA on cycle day 2, mean FSH,
      LH, and E2 levels were significantly elevated over the baseline levels. Following
      no LA on cycle day 3 or 4, a repeat dose of 25 micrograms LA caused a second
      flare of LH and E2 on cycle day 6. Of the 14 cycles, 6 were canceled because of
      poor stimulation. Two of the eight patients who underwent retrieval delivered a
      live birth. CONCLUSIONS: This is the first study to examine both the pituitary
      response and the recovery time from minidose follicular-phase GnRHa. An extremely
      small dose of LA is needed to cause a pituitary flare of gonadotropins. Following
      a flare from 25 micrograms of LA on cycle day 2, the pituitary is able to recover
      and respond with a repeat flare on cycle day 5.

PMID- 8739055
TI  - The initial flare-up induced by gonadotropin releasing hormone agonist may serve
      as a predictor of ovarian response in the current IVF-ET treatment cycle in
      normogonadotropic women aged 40-48 years.
AB  - OBJECTIVE: Our purpose was to assess the potential role of the baseline hormone
      profile in combination with the initial pattern of response to gonadotropin
      releasing hormone (GnRH) analogue in predicting ovarian function and hence
      reproductive outcome in normogonadotropic patients aged 40 years or older
      undergoing IVF treatment. PATIENTS AND METHODS: A retrospective analysis of 394
      controlled ovarian hyperstimulation (COH) cycles that reached the stage of oocyte
      retrieval was conducted. The study included 163 normogonadotropic (serum FSH < or
      = 15 IUIL) patients aged between 40 and 48 years who had regular menstrual
      cycles. Superovulation was achieved using menotropins in combination with GnRH
      analog (short protocol, beginning on menstrual day 2). The ovarian response was
      monitored on the third cycle day, the day following the first GnRH analogue
      administration. RESULTS: Cycle distribution by patient age was 175 (44.4%), 122
      (30.9%), and 97 (24.7%), while the patient distribution was 85 (52.2%), 48
      (29.5%), and 30 (18.3%) for age groups 40-41, 42-43, and 44-48 years,
      respectively. The mean total dose of menotropins needed for optimal COH was 1787
      IU (range, 600-6000 IU). This dose increased with age, while the yield of oocytes
      and embryos declined (P < 0.05; ANOVA). A positive correlation was demonstrated
      between the E2 level on day 3 (GnRH analogue flare effect) and the outcome of the
      treatment cycle (number of oocytes and embryos). Using multiple stepwise
      regression analysis, it was demonstrated that the initial (day 3) serum E2
      levels, combined with baseline FSH levels, patients's age and body mass index
      enabled early prediction of the ovarian response in the current IVF-ET treatment
      cycle (oocytes = 8.2 - 0.18 x Age + 0.17 x BMI - 0.12 x FSH + 0.0042 x E2).
      CONCLUSIONS: Multiple-parameter analysis demonstrated that the use of the initial
      E2 response to GnRH analogue stimulation combined with basic clinical data may
      assist in the prediction of ovarian function and hence the reproductive outcome
      in normogonadotropic IVF patients aged 40 years or older. This may serve as a
      clinical tool for improving patient selection and treatment outcome in IVF-ET.

PMID- 8739056
TI  - Elective cryopreservation of all embryos in women at risk of developing ovarian
      hyperstimulation syndrome may not prevent the condition but reduces the live
      birth rate.
AB  - OBJECTIVE: Our goal was to evaluate the use of elective cryopreservation of all
      embryos to prevent the development of ovarian hyperstimulation syndrome in
      patients at risk while undergoing in vitro fertilization treatment. DESIGN: We
      analyzed 117 treatment cycles in which the serum E2 concentration on the day of
      hCG administration was > 10,000 pM and in whom > or = 15 oocytes were retrieved
      at ultrasound-directed follicle aspiration. The incidence of ovarian
      hyperstimulation syndrome, pregnancy, and live birth in 65 patients who had
      elective cryopreservation of all embryos and 52 patients who had fresh embryo
      transfer were compared. Independent t test and chi-square test (with Yates'
      correction) was used as appropriate. RESULTS: The clinical pregnancy (35 vs 17%;
      P < 0.03) and the live birth (27 vs 12%; P < 0.05) rates in patients receiving
      fresh embryo transfer was significantly higher than in those who had elective
      cryopreservation of all embryos. The incidence of moderate and severe ovarian
      hyperstimulation syndrome was similar in both groups (3.8 and 6.2%). CONCLUSIONS:
      Elective cryopreservation of all embryos does not reliably protect against the
      development of ovarian hyperstimulation syndrome but may reduce the clinical
      pregnancy and live birth rate.

PMID- 8739057
TI  - The screening of tubal abnormalities in the infertile couple.
AB  - PURPOSE: Our goal was to assess, with a prospective study, the role of
      hysterosalpingo-contrast sonography (HyCoSy) with an echocontrast agent and
      transvaginal ultrasonography alone in the evaluation of tubal status. METHODS:
      Thirty patients were included in the study. These patients underwent an initial
      plain transvaginal ultrasound examination the day before the HyCoSy. The findings
      obtained from both examinations were compared with laparoscopic diagnosis,
      performed in the same menstrual cycle. RESULTS: The kappa values were 0.48 for
      patency evaluation and 0.67 for the diagnosis of the presence of at least one
      patent tube, suggesting a good agreement in both cases between HyCoSy and
      surgery. HyCoSy had a significantly lower sensitivity (50%), but not a
      significantly higher specificity (75%), than transvaginal ultrasonography alone
      in the diagnosis of tubal infertility-related abnormalities such as peritubal
      adhesions. CONCLUSIONS: The study demonstrates that the HyCoSy is a useful test
      when scheduling the most suitable treatment for infertile couples.

PMID- 8739058
TI  - Sperm immobilization antibodies in infertile male sera decrease the acrosome
      reaction: a possible mechanism for immunologic infertility.
AB  - OBJECTIVE: To study the effect of sperm-immobilizing antibodies from male sera on
      spontaneous and A23187-induced acrosome reactions (AR). DESIGN: Swim-up
      spermatozoa obtained from three fertile donors were incubated with 13 sera with
      sperm-immobilizing antibodies obtained from infertile men and three control sera
      obtained from healthy fertile males. Sperm acrosomes were examined by staining
      with pisum sativum agglutinin labeled with fluorescein isothiocyanate (30
      micrograms/ml; Sigma Chemical Co., St. Louis. MO) as spontaneous and A23187 (used
      at a final concentration of 10 microM; Sigma Chemical Co.) induced. RESULTS: The
      incidence of spontaneous AR of spermatozoa incubated with antisperm antibody
      positive male sera (6.2 +/- 0.7) was significantly (P < 0.001) lower than that of
      spermatozoa incubated with control sera (10.7 +/- 0.5). And the incidence of
      A23187-induced and -inducible (incidence of induced minus spontaneous) ARs of
      spermatozoa incubated with sperm antibody-positive male sera (12.4 +/- 1.9 and
      6.2 +/- 1.9) was significantly lower (P < 0.001) than that of spermatozoa
      incubated with control sera (31.0 +/- 0.5 and 20.3 +/- 0.9). Sperm-immobilizing
      antibody-positive sera decreased spontaneous, A23187-induced, and inducible ARs.
      CONCLUSIONS: Sperm-immobilizing antibodies from male sera interfere with
      fertilization by inhibiting the AR.

PMID- 8739059
TI  - Coculture of human spermatozoa with reproductive tract cell monolayers can
      enhance sperm functions better than coculture with Vero cell monolayers.
AB  - PURPOSE: In order to develop a better system for support of human sperm function
      in vitro, we conducted studies to evaluate whether reproductive tract cells are
      better than non-reproductive tract cells as an adjunt in that regard. METHODS:
      Human spermatozoa were cocultured with Vero cells, with human oviduct cells and
      endometrial cells, and without cells (control) for either 1, 4, or 24 hr. Sperm
      motility was then analyzed with a computer-aided sperm analyzer (CASA-Hamiliton
      Thron, HTM IVOS Motility Analyzer). Aliquots of spermatozoa incubated for 24 hr
      were also stained with Hoechst 33258 and FITC-PNA to evaluate the status of
      acrosome in live cells. RESULTS: Significant differences (P < 0.05) between the
      oviduct cell and the control groups after 24 hr were evident in the curvilinear
      velocity (VCL) (81.4 +/- 13.4 vs 60.0 +/- 14.1 microns/sec) and amplitude of
      lateral head displacement (ALH) (5.2 +/- 0.6 vs 4.1 +/- 0.5 microns). The
      incidence of acrosome reaction of live sperm was significantly higher in the
      endometrial cell group than in the controls (25.4 +/- 9.9 vs 6.6 +/- 2.4%; P <
      0.001). CONCLUSIONS: Coculture with human reproductive tract cells seems to
      improve some functional parameters of human spermatozoa. Coincubation with such
      cell lines, especially oviduct cells, might be a feasible approach to
      optimization of human spermatozoa for assisted fertilization using subfertile or
      frozen-thawed samples. We think coincubating human spermatozoa with a human
      reproductive tract cell line, especially oviduct cells, might be a feasible
      approach in preparing human spermatozoa for assisted fertilizatioin in subfertile
      and frozen-thawed semen samples.

PMID- 8739060
TI  - Optimizing tubal epithelial cell growth promotes mouse embryo hatching in
      coculture.
AB  - PURPOSE: This study investigates the relationship between human tubal epithelial
      cell growth characteristics and mouse embryonic development to determine which
      cellular requirements should be preferentially provided in a coculture system.
      METHODS: Cell growth and viability were assessed for 5 days in alpha-minimal
      essential medium or human tubal fluid supplemented with 10% human serum or 10%
      synthetic serum. Two-cell mouse embryo development to blastocyst and hatching
      blastocyst stages was also assessed with or without coculture. RESULTS: Both
      epithelial cell growth and embryo development were dependent on serum
      supplementation with better cell viability and growth rates in human serum and
      better blastocyst development in synthetic serum. The highest proportion of
      hatching blastocysts was found in alpha-minimal essential medium and human serum
      with coculture. CONCLUSIONS: Culture conditions which improve tubal epithelial
      cell growth also improve the hatching rate of mouse embryos in coculture. This
      indicates that by meeting the metabolic and nutritional demands for epithelial
      cell growth, the beneficial effects of coculture on embryo development may be
      optimized.

PMID- 8739061
TI  - Mouse oocytes injected with cryopreserved round spermatids can develop into
      normal offspring.
AB  - PURPOSE: This study was performed to determine whether frozen-thawed mouse round
      spermatids can fertilize oocytes and contribute to normal embryo development.
      METHODS: Freshly collected mouse testicular cells were frozen in PBS containing
      7.5% glycerol and 7.5% fetal bovine serum. After thawing and removal of the
      cryoprotectants, round spermatids were selected and injected individually into
      mature oocytes which had been previously activated with Sr(2+)-containing Ca(2+)
      free medium. RESULTS: After thawing, 75-85% of testicular cells were alive. About
      90% of the oocytes were fertilized by intracytoplasmic injection of frozen-thawed
      round spermatids; 11% (17/150) of embryos transferred to foster mothers developed
      into normal offspring. CONCLUSIONS: Mouse round spermatids can be cryopreserved
      for production of normal offspring.

PMID- 8739063
TI  - Pregnancy in a woman with Turner mosaicism following ovarian stimulation and in
      vitro fertilization.
AB  - We conclude that women with Turner mosaicism (46XX/45XO) and normal FSH levels
      may have an adequate ovarian reserve and undergo attempts at traditional assisted
      reproduction. At the time of retrieval an ovarian biopsy may be performed in
      order to evaluate directly the ovarian karyotype. A successful pregnancy resulted
      from oocytes retrieved from the gonad demonstrating a normal karyotype.

PMID- 8739062
TI  - In vitro development of spontaneously activated bovine oocytes.
AB  - PURPOSE: The aim of this study was to compare the development of bovine
      parthenogenetic and in vitro fertilization-derived (IVF) embryos. Oocytes were
      matured, fertilized, or allowed to activate spontaneously by aging and then
      cultured for up to 14 days in vitro. Cleavage and development rates, morphology,
      ultrastructure, and transcriptional activity were compared. RESULTS: Very few
      parthenogenotes (7.5% of aged oocytes) were obtained and none developed to the
      hatched blastocyst stage. The pattern of 3H-uridine incorporation at the two-,
      four-, and eight-cell stages was similar in both types of embryos. Morphological
      study, however, revealed that none of the parthenogenotes showed features
      associated with long-term development: they were developmentally delayed and
      usually arrested before reaching the blastocyst stage (only 0.5% of aged oocytes
      developed to the blastocyst stage). Structural differences between
      parthenogenotes and the IVF-derived embryos were observed at all stages of
      development. CONCLUSIONS: Structural observation suggested that failure of long
      term development of bovine parthenogenotes may have a metabolic basis. Some
      functional changes appeared to coincide with chronological age rather than
      developmental age. Even though development of parthenogenotes was limited; some
      features of nuclear maturation and activation of the embryonic genome occur
      without contribution of the paternal genome.

PMID- 8739065
TI  - Laparoscopy after multiple follicle aspirations fails to demonstrate pathology in
      oocyte donors.

PMID- 8739064
TI  - Successful percutaneous epididymal sperm aspiration (PESA) after more than 20
      years of acquired obstructive azoospermia.

PMID- 8739066
TI  - Transcervical intrauterine embryo transfer (ET) with a new everting catheter and
      "peel-back" technique.

PMID- 8739067
TI  - Government and bureaucratic bioethics: addressing moral issues in the service of
      ideology.

PMID- 8739068
TI  - Privacy and autonomy: from Warren and Brandeis to Roe and Cruzan.
AB  - Warren and Brandeis' tort against invasion of privacy had chiefly a social goal:
      to enlist the courts to reinforce the norm of civility. Years later in Griswold
      v. Connecticut (1965), the Supreme Court announced a constitutional right of
      privacy that was personal in focus. Here and in subsequent rulings on abortion
      and the "right to die, " it became apparent that Warren and Brandeis' Victorian
      "right to be let alone" had metamorphosed into a right to autonomy, whose
      amoeboid contours made prediction or even description a tricky business. But
      privacy is an unsatisfactory proxy for autonomy, and perhaps for this reason has
      dwindled in importance as a rationale in these areas.

PMID- 8739069
TI  - Routine neonatal circumcision: symbol of the birth of the therapeutic state.
AB  - The religious justification for male circumcision proffered by Jewish and Islamic
      parents is frequently overlooked in current secular (medical/hygienic)
      discussions that (1) challenge the moral justification of this ancient practice,
      and (2) question the decisions of today's parents who are committed, on the basis
      of their religious beliefs, to continue this practice. This paper reviews
      critically these conflicting values and arguments and calls for compromise in the
      face of potential state intervention to coerce parents to abandon this practice.

PMID- 8739070
TI  - Moral consensus in public ethics: patient autonomy and family decision-making in
      the work of one state bioethics commission.
AB  - Focusing on the work of one bioethics commission, the New York State Task Force
      on Life and the Law, this article explores the role played by moral consensus in
      public ethics. Task Force members, who were appointed to represent diverse
      interests in New York State, identified a culturally strong value of individual
      autonomy as the ethical basis for their work on life-sustaining treatment. This
      moral consensus permitted the members to unite across their differences and
      develop public policy recommendations that substantially reformed a highly
      troubling New York law. However, the principle of autonomy insufficiently guides
      decisions by caring family members for incompetent adults in cases where little
      is known of patient preference. A different, more innovative moral vision is
      required--one that grants a more robust moral authority to the family. While
      government efforts that rely on moral consensus developed in a broad-based and
      well-reasoned manner can serve us well, in some cases the consensus will provide
      inadequate moral guidance. Government bioethical efforts must guard against the
      limits of moral vision in light of their disproportionate societal power.

PMID- 8739071
TI  - Ethical principles in federal regulations: the case of children and research
      risks.
AB  - Ethical principles play an important part not only in the promulgation of
      regulations but also in their application, i.e., enforcement and adjudication.
      while traditional ethical principles--promotion of welfare, freedom, and fairness
      -play an important role in both elements of regulation, some other kinds of
      ethical principles are significant as well. Principles governing the structure of
      decision processes should shape the structure and actions of agencies; principles
      of wise application should govern the work of those whose responsibility it is to
      apply regulatory language to particular situations. These points are demonstrated
      by investigating a case study: federal regulations designed to protect children
      involved in scientific research applied to a placebo study of the effects of
      recombinant human growth hormone on children of extremely short stature.

PMID- 8739072
TI  - Ethical assumptions and ambiguities in the Americans With Disabilities Act.
AB  - The Americans With Disabilities Act (ADA) promotes social justice by protecting
      disabled persons from discrimination and prejudice. It seeks equality of
      opportunity for them and protects their well being by giving them fair access to
      goods, services and benefits. These rights are circumscribed in the ADA, however,
      by constraints of cost, efficiency, utility, and certain social mores. The ADA
      offers little direction about how to set priorities when these values come into
      conflict, or about whether equality or opportunity favors equivalent or
      preferential treatment for disadvantaged people. Until these ambiguities and
      potential value conflicts are resolved, a central moral and social problem
      remains unresolved: How can we demonstrate commitment to the rights and welfare
      of those with severe disabilities while placing fair limits upon their claims?
      Five special concerns are discussed: (1) eligibility and the allocation of health
      care; (2) the meaning of 'qualified but disabled' in employing people with mental
      disabilities; (3) equal opportunity and problems of envy and malingering; (4) ADA
      accommodation and public protection through testing and licensure; and (5) ADA
      protection and problems of backlash. Rather than simply wait to see what courts
      and administrative agencies decide, we should evaluate the moral conflicts,
      articulate criteria, and help make some difficult choices on morally defensible
      grounds.

PMID- 8739073
TI  - (In) equality, (ab) normality, and the Americans With Disabilities Act.
AB  - The 1990 Americans with Disabilities Act enacted a conceptual shift in the
      meaning of 'disability.' Rather than defining 'disability' as a disadvantageous
      physical or mental deficit of persons, it codifies the understanding of
      'disability' as a defective state of society which disadvantages these persons.
      In contrast, the standard medical model incorrectly conceptualizes disabled
      persons as biologically inferior, and thus confines them to the role of
      recipients of benevolence or care. Turning to an ethic of caring yields counter
      intuitive results that conflict with the conceptual apparatus of the ADA. It is
      argued that in order to liberate social marginalized to being socially enabled,
      one must re-conceptualize current practice by adopting the ADA's conceptual
      framework.

PMID- 8739074
TI  - Ambiguities and irresolvable tensions in the ADA: a reply to Loretta M. Kopelman
      and Anita Silvers.
AB  - This essay comments on the articles by Loretta M. Kopelman and Anita Silvers. It
      extends their analyses and concludes that consistency and the total absence of
      conflict may be unavailable when one interprets and applies the Americans with
      Disabilities Act.

PMID- 8739075
TI  - Nutrition and breast cancer risk: can an effect via insulin resistance be
      demonstrated?
AB  - It is postulated that the metabolic/endocrine concomitants of insulin resistance
      resulting from high animal fat intake and weight gain after the age of 30 could
      be contributing to the increasing incidence of postmenopausal breast cancer and
      recent changes in its biologic characteristics. Case/control studies have shown
      that hyperinsulinaemia and abdominal obesity, which are recognized as markers of
      insulin resistance, are risk markers for postmenopausal breast cancer also.
      Excess weight gain linked to high dietary intake of saturated fat is thought to
      be a major cause of insulin resistance. The hypothesis is compatible with the
      "breast tissue age" model for breast cancer risk. Biological evidence suggests
      that the concomitants of insulin resistance may stimulate growth activity in
      existing breast cancer also. The hypothesis that nutritional factors which favour
      hyperinsulinaemia may also favour breast cancer growth can be tested. Restriction
      of dietary fat and high intake of fibre and complex carbohydrate have been shown
      to normalise insulin levels in a proportion of subjects with hyperinsulinaemia.
      Restriction of dietary fat intake has also been shown to reduce bioavailable
      oestrogen levels in healthy postmenopausal women. A randomised trial of a low
      fat, high fibre, high complex carbohydrate regimen is proposed as adjuvant
      treatment following primary surgery in postmenopausal women with early breast
      cancer. A cancer preventive or delaying ability can be assessed by comparing the
      incidence of contralateral second breast cancer and the metastasis rate in the
      diet and control groups. Insulin levels, abdominal obesity, and body mass should
      be monitored although normalisation of insulin levels need not necessarily
      involve decrease in body mass.

PMID- 8739076
TI  - Quantification of prostate-specific antigen immunoreactivity in human breast cyst
      fluids.
AB  - The frequency of gross cystic breast disease in premenopausal women and its
      possible association with increased breast cancer risk emphasises the importance
      of investigations relating to breast cyst fluid composition. In order to
      contribute to a better analysis of this medium, we have measured the presence of
      prostate-specific antigen immuno-reactivity in sixty-four human breast cyst
      fluids. Data analyses show that 35% of samples presented a level of this antigen
      < 0.05 micrograms/L, whereas 42 out of 64 cysts show a significant increase in
      the mean value of metabolically active apocrine cysts when compared to flattened
      cysts (p < 0.01). We report the first evidence that breast epithelium of gross
      cysts produces, secretes, and accumulates large amounts of prostate-specific
      antigen, a glycoprotein produced by prostatic tissue but recently detected in
      breast tumours, normal tissues, and during pregnancy. The production and
      intracystic accumulation of this serine protease in biosynthetically active
      apocrine type cyst can play a feasible role in the natural history gross cystic
      breast disease as well as in the mechanism of cyst formation, enlargement, and
      transformation.

PMID- 8739077
TI  - Regularity and length of menstrual cycles in women aged 41-46 in relation to
      breast cancer risk: results from the DOM-project.
AB  - The effect of regularity and length of the menstrual cycle on breast cancer risk
      was studied prospectively in 78 cases and 383 age-matched controls who
      participated in a breast cancer screening programme, the DOM-project, in Utrecht,
      the Netherlands. Before entering the screening programme when they were aged 41
      46, the women kept a menstrual calendar during at least three consecutive cycles.
      Cycles were considered to be irregular if any of three cycles was shorter than 21
      days or longer than 35 days and/or if variation between cycle lengths was more
      than five days. Women with irregular cycles had a significantly reduced risk of
      breast cancer (odds ratio = 0.44; 95% confidence interval 0.22-0.86) after
      adjustment for age at menarche, age at first birth, parity, Quetelet's index and
      family history of breast cancer. Among regularly menstruating women, long cycles
      (28 days or more) were not significantly associated with increased risk of breast
      cancer (odds ratio 1.17; 95% confidence interval 0.66-2.09). To the extent that
      irregular menstrual cycles reflect anovulatory cycles, our findings support the
      hypothesis that the cumulative number of regular ovulatory cycles increases
      breast cancer risk.

PMID- 8739078
TI  - Prostate specific antigen--a new constituent of breast cyst fluid.
AB  - We demonstrate for the first time that prostate specific antigen (PSA) is a
      component of breast cyst fluid. At the cutoff level of 0.01 or 0.03 micrograms/L
      of PSA, 64% or 43% of cyst fluids are positive for PSA, respectively. PSA in cyst
      fluid, as characterized by high performance liquid chromatography, exists in
      almost equal concentrations as free PSA, with a molecular weight of 33 KDa, and
      as PSA bound to alpha 1-antichymotrypsin, with a molecular weight of 100 KDa. PSA
      presence was also characterized in cyst fluid by Western blot analysis. These
      data suggest that PSA is a frequent component of breast cyst fluid. More studies
      are needed to establish the role of this serine protease in normal breast, gross
      breast cystic disease, and breast cancer.

PMID- 8739079
TI  - S-phase fraction identifies high-risk subgroups among DNA-diploid breast cancers.
AB  - The prognostic value of DNA content measured by means of flow cytometry was
      analyzed in formalin-fixed, paraffin-embedded samples from 231 breast cancer
      patients treated between 1984 and 1988, with a mean follow-up period of 55
      months. We followed the guidelines of a Consensus Meeting held on this issue in
      Maine, USA, in 1992. DNA-diploid and -aneuploid tumors were evaluated separately
      for the fraction of cells in S-phase (SPF) contained in them, this being divided
      into three groups ('high', 'intermediate', and 'low'), defined by the 25th and
      75th centile of the SPF-distribution corresponding to either DNA-diploid or DNA
      aneuploid tumors. Unequivocally readable histograms were obtained from 174
      samples (75.3%). A high SPF in diploid tumors was significantly associated with a
      higher recurrence rate (p = 0.015), a shorter disease-free survival (p = 0.014),
      advanced (IIIB) clinical stage (p = 0.034), and almost significantly with total
      survival (p = 0.055). In a multivariate Cox regression analysis, a high SPF in
      diploid tumors retained its independent prognostic power, being significantly
      associated with a shorter disease-free survival (p = 0.00049) and total survival
      (p = 0.0077). It also allowed to identify a subgroup with an ominous prognosis
      among patients < or = 50 years of age with early stage tumors. Our results fully
      validate the recommendations of the 1992 Maine Consensus Meeting.

PMID- 8739080
TI  - Salvage chemotherapy in metastatic breast cancer: an experience with the
      combination of mitoxantrone, 5-fluorouracil, and L-leucovorin.
AB  - From January 1992 to July 1993, 28 patients with metastatic breast cancer were
      entered in a phase II trial to assess the activity and toxicity of the
      combination of mitoxantrone, 5-fluoruracil, and leucovorin. Patients were
      eligible if they had progressive disease after either adjuvant (2 patients) or
      previous chemotherapy for metastatic disease (26 patients). Twenty-five patients
      (89.2%) had received previous anthracycline-based therapy. Predominant site of
      metastatic disease was visceral in 22 patients, bone in 2 patients, soft tissue
      in 4 patients, and the majority of patients (89.2%) had two or more sites of
      disease. The regimen was administered according to the following schedule:
      Mitoxantrone 9-12 mg/m2 i.v. on day 1; L-Leucovorin 150 mg i.v. over 1 hour
      before 5-Fluorouracil 350 mg/m2 i.v. push days, 1, 2 and 3. Courses were repeated
      every 21 days. Twenty-six patients were evaluable for response. We observed 2
      complete responses, 5 partial responses with a median duration of 38 weeks (range
      23-68). The objective response rate was 27% (95% C.I., 10% to 44%). Myelo
      suppression was the most frequent toxicity, but it was mild in the majority of
      patients. Nine episodes of fever and neutropenia occurred in six patients but
      none of these episodes was fatal. No clinical evidence of cardiotoxicity was
      observed. At a median follow-up of 78 weeks, the median time to progression was
      20.5 weeks and the median overall survival was 48 weeks. We conclude that this
      regimen is well tolerated and in our experience the objective response rate is
      similar to other salvage chemotherapy regimens.

PMID- 8739081
TI  - Impaired hemorheology in patients with postmastectomy lymphedema.
AB  - Lymphedema of the arm is one of the most disabling and serious complications of
      breast cancer. Apart from tumor infiltration or fibrosis of lymphatic pathways,
      little is known about factors favoring the development of lymphedema. In the
      present study, we investigated the impact of rheologic parameters, e.g. red cell
      aggregation (EA) and plasma viscosity (PV), and of capillary morphology and
      capillary flow in patients with breast cancer with (n = 18) and without (n = 18)
      lymphedema. Patients with lymphedema showed a significant increase of red cell
      aggregation (p < 0.001) that indicates a systemic component of lymphedema and
      might offer a possibility of prevention and therapy of this condition. A hitherto
      unclassified protein factor favoring red cell aggregation and lymphedema might be
      postulated.

PMID- 8739082
TI  - Tumor proliferative activity and response to first-line chemotherapy in advanced
      breast carcinoma.
AB  - The relationship between tumor proliferative activity and response to first-line
      chemotherapy and survival was investigated in 76 advanced breast cancer patients.
      Proliferative activity was determined by means of Ki-67 immunohistologic staining
      on primary tumors (55 patients) or at the relapse site (21 patients), and was
      classified as low ( < or = 25% of stained cells) or high ( > 25% of stained
      cells). The usual WHO response criteria were used. The median duration of follow
      up was 18 months (range 3-58). Forty-seven patients (62%) had tumors with low,
      and 29 (38%) had tumors with a high rate of proliferative activity. The two
      groups were well balanced in terms of important variables such as disease-free
      survival, performance status, age, menopausal status, and the type of first-line
      chemotherapy (anthracycline-based regimens versus cyclophosphamide-methotrexate-5
      fluorouracil). The estrogen receptor (ER) content, measured by means of
      immunohistochemical assay, was markedly different in the two groups, with 27/47
      tumors with low proliferative activity (57%) and 6/29 with high-proliferative
      activity (21%) being ER positive ( > or = 45% of stained cells) (p = 0.003).
      Moreover, a significant difference in the metastatic pattern was also evident,
      with a higher incidence of bone and a lower incidence of soft tissue metastases
      in the group of patients with tumors with low proliferative activity (p = 0.004).
      Overall, 10/47 responses (21%: PR = 7, and CR = 3) were observed in the group
      with a low rate of proliferative activity, versus 14/29 (48%: PR = 9, and CR = 5)
      in the group with highly proliferative tumors, the difference being statistically
      significant (p = 0.03). When a multivariate analysis was performed, the only
      factor that retained independent prognostic significance was the predominant site
      of disease, particularly soft tissues (p = 0.003). Despite the difference in
      response rate, when survival analysis was performed according to the Kaplan-Meier
      method, no significant difference was observed in the two groups, but when the
      analysis was limited to responsive patients, the median survival observed in
      those with a low and those with a high rate of proliferation was 35 and 19 months
      respectively (p = 0.02). The same results were obtained when multivariate
      survival analysis was carried out using Cox's regression model. These data
      suggest that there is a link between tumor proliferative activity and response to
      chemotherapy in advanced breast cancer, and may indicate the need to use more
      intensive treatments in selected patients with highly proliferative tumors.

PMID- 8739083
TI  - A fibroadenoma with a t(4;12) (q27;q15) affecting the HMGI-C gene, a member of
      the high mobility group protein gene family.
AB  - An intracanalicular fibroadenoma of the breast showing a clonal chromosomal
      aberration t(4;12) (q27;q15) as the sole cytogenetic abnormality is described. In
      order to narrow down the breakpoint region on chromosome 12 on the molecular
      level we performed fluorescence in situ hybridization (FISH) analysis with a
      cosmid pool originating from a YAC-contig overspanning part of the region 12q14
      15. We were able to narrow down the breakpoint to an approximately 230kb fragment
      belonging to the HMGI-C gene which maps within an area recently designated as MAR
      (Multiple Aberration Region). The chromosomal breakpoints of other frequent
      benign solid tumors, i.e. lipomas, uterine leiomyomas, and pleomorphic adenomas
      are clustered within the third intron of that gene.

PMID- 8739084
TI  - Parity, age at first and last birth, and risk of breast cancer: a population
      based study in Sweden.
AB  - Associations between parity and the risk of breast cancer, and the relative
      importance of age at first and age at last birth on breast cancer risk, were
      estimated in a case-control study nested in a nation-wide cohort of Swedish women
      born between 1925 and 1960. A total of 12,782 women with breast cancer and five
      times as many individually age-matched controls, aged less than 60 years with
      concomitant fertility information, were included in the analysis. Increasing
      parity was associated with a pronounced decrease in the risk of breast cancer
      with each additional birth conferring a 10 percent risk reduction (odds ratio
      0.90 [95% CI 0.88-0.91]). In an analysis limited to women with two or more
      parities, and after adjustment for the effects of ages at interim births, the
      risk of breast cancer increased by about 13 percent for each five-year increment
      in age at first birth (odds ratio 1.13 [1.08-1.19]). For every five year-increase
      in age at last birth there was a small risk increase of marginal statistical
      significance (odds ratio 1.05 [1.01-1.09]). The present findings contradict
      recent claims that age at last birth has a stronger effect than age at first
      birth on breast cancer risk. The dominance of age at first birth as risk
      modulator is likely to reflect the protection afforded by the terminal
      differentiation of breast cells induced by a first pregnancy.

PMID- 8739086
TI  - Prognostic characteristics in breast cancers after hormone replacement therapy.
AB  - We examined the influence of hormone replacement therapy (HRT) on breast tumour
      biology by comparing the prognostic characteristics of breast cancers and
      survival in 121 women prescribed replacement hormones before diagnosis with those
      in 1468 women without such treatment. The women receiving HRT had a lowered
      relative risk of being diagnosed with tumours of more than 20 mm in diameter, OR
      = 0.7 (CI 0.5-1.0) and axillary lymph node dissemination, OR = 0.7 (CI 0.4-1.1).
      These risk reductions were most pronounced and statistically significant in the
      women who had been prescribed a combined estradiol-progestin regimen. The
      patients in this compound group also had a diminished relative risk of having
      poorly differentiated tumours. Further, there was an indication that the women
      prescribed HRT, and especially those with conjugated estrogens/estradiols alone,
      had a decreased relative risk of developing aneuploid tumours. There was no clear
      pattern for women receiving the biologically weak oestriol, although risk
      estimates were generally higher for unfavourable tumours in comparison with those
      receiving the higher potency compounds. Adjustments for indications of earlier
      detection (i.e. lead time bias) did not influence the pattern or magnitude of the
      risk estimates. No association between any type of HRT and survival after breast
      cancer diagnosis was noted, but analyses were based only on 19 breast cancer
      deaths among exposed patients. We conclude that breast cancers occurring after
      treatment with HRT, especially the combined estrogen-progestin regimen, seem to
      have more favourable tumour features than tumours in non-treated women. Our
      findings may reflect a less aggressive biological behaviour of breast cancers in
      women receiving HRT, or in part be explained by the earlier detection of the
      tumours in these women.

PMID- 8739085
TI  - Expression of L-PHA-binding proteins in breast cancer: reconstitution and
      molecular characterization of beta 1-6 branched oligosaccharides in three
      dimensional cell culture.
AB  - Expression of beta 1-6 branched oligosaccharides in human breast cancer cells was
      investigated in vivo and in vitro. Lectin histochemical and lectin blotting
      analyses of surgically resected specimens were performed using L-PHA (phaseolus
      vulgaris leukoagglutinin) lectin, which binds to beta 1-6 oligosaccharides. The
      glycoproteins bearing beta 1-6 oligosaccharides of breast cancer tissues were
      found to be 170 kD and 120 kD in molecular weight, and the former appeared to be
      an epitope of carcinoembryonic antigen (CEA). The beta 1-6 oligosaccharides were
      expressed in both cancer cell lines at the outer layer of the colonies when
      cultured in type I collagen, but not in agarose gel. No correlation was observed
      between beta 1-6 expression and cell cycle. The beta 1-6 oligosaccharides did not
      coincide with breast cancer-associated antigens, such as CEA, MUC1, and cathepsin
      D. The beta 1-6 oligosaccharides of these cell lines were markedly inhibited when
      swainsonine, a mannosidase II inhibitor, was added to the culture medium. The 120
      kD molecule, which was obtained from MCF-7 cells cultured in type I collagen gel,
      was consistent with that of breast cancer tissues and was similar to lysosome
      associated membrane glycoproteins (LAMPs). The results suggest that the
      glycoproteins bearing beta 1-6 branched oligosaccharides in human breast cancer
      incorporate an epitope of CEA and human LAMPs and that the expression of LAMPs
      may depend on their surrounding matrices and may play an important role in cancer
      invasion or metastasis.

PMID- 8739087
TI  - Glucocorticoid receptor concentration modulates glucocorticoid-regulated gene
      expression in rat pancreatic AR42J cells.
AB  - In this study we investigated the effects of altered intracellular glucocorticoid
      receptor (GR) concentrations on glucocorticoid-regulated gene expression in the
      rat pancreatic acinar cell line AR42J. Incubation of AR42J cells with
      dexamethasone results in a time-dependent transcriptional stimulation of amylase
      gene expression (about 5-fold) and a transcriptional inhibition of bombesin
      receptor (BR) gene expression. Decreasing the intracellular GR concentration to
      50% by preincubation with RU 38486 results in a significant attenuation of
      dexamethasone-regulated amylase and BR gene expression. In contrast, increasing
      the intracellular GR concentration 2-fold by preincubation with the
      phosphodiesterase inhibitor IBMX significantly enhances the glucocorticoid
      inhibition of BR gene expression whereas amylase mRNA concentrations remain
      unaltered. These data demonstrate that intracellular GR concentrations determine
      the sensitivity of glucocorticoid-regulated gene expression in rat pancreatic
      AR42J cells.

PMID- 8739088
TI  - Gallbladder emptying and cholecystokinin response to fish oil and trioleate
      ingestion.
AB  - The aim of the present study was to compare gallbladder emptying, gastric
      emptying and release of cholecystokinin (CCK), gastrin and secretin after
      intragastric administration of fish oil and trioleate. After intravenous
      injection of 99mTc-HIDA, 30 ml of a lipid labelled with 111In was administered
      through a gastric tube. Using dual scintigraphy with two markers, gallbladder and
      gastric emptying were measured simultaneously for 120 min. Plasma concentrations
      of gastrin, secretin and CCK, were determined throughout the period. The emptying
      of the gallbladder was reduced by 27% and the release of CCK by 85% after fish
      oil as compared with trioleate. Gastric emptying as well as the release of
      gastrin and secretin were similar after the two types of fat. The results suggest
      that the reduced gallbladder emptying after fish oil may be due to a smaller
      release of CCK.

PMID- 8739089
TI  - Liver function in patients with pulmonary emphysema due to severe alpha-1
      antitrypsin deficiency (Pi ZZ).
AB  - Alpha 1-Antitrypsin deficiency predisposes to pulmonary emphysema, liver
      cirrhosis and hepatocellular carcinoma. Anecdotal evidence and a large autopsy
      study suggest that severe lung and liver disease rarely coexist in the same
      subject, but this has not been studied in patients. Therefore we investigated 27
      patients with severe alpha 1-deficiency (Pi ZZ) and pulmonary emphysema for signs
      of liver disease and impaired hepatic function. A subgroup of 7 patients
      underwent quantitative liver function tests. On physical examination or
      ultrasonography, cirrhosis or tumor was not suspected in any patient.
      Conventional liver function tests were completely normal in 17 patients. Elevated
      serum activities of gamma-glutamyltranspeptidase and/or aminotransferases were
      seen in 10 patients. In some, the elevation was only marginal and in none more
      than twice normal. The serum bilirubin concentration and activity of alkaline
      phosphatase were increased in 1 patient. Serum protein, albumin, fibrinogen,
      antithrombin III, alpha 1-fetoprotein concentrations, serum activities of
      cholinesterase and glutamate dehydrogenase, activated partial thromboplastin time
      and prothrombin time were normal in all patients. The indocyanine green half-life
      was abnormal only in 1 of 6 patients, suggesting that hepatic blood flow was not
      impaired in the study group. However, the lidocaine half-life and galactose
      elimination capacity, parameters of hepatic metabolization, were impaired in 4
      and 6 of 7 patients, respectively. We conclude that liver disease or impaired
      liver function is not a clinically relevant problem in most patients with
      pulmonary emphysema due to alpha 1-antitrypsin deficiency. But results of
      quantitative liver function tests, although performed in only a small group of
      patients, suggest that hepatic metabolization might be impaired even in those
      patients who present with pulmonary disease.

PMID- 8739090
TI  - Changes in urinary nitrate and nitrite during treatment of ulcerative colitis.
AB  - The urinary excretion rates of nitrate (NO3) and nitrite (NO2) were monitored in
      14 patients with active ulcerative colitis during treatment using hydrocortisone
      and sulfasalazine. During the active phase of the disease, the NO3 excretion was
      significantly higher in the patients than in healthy controls (n = 6, p < 0.05),
      although it varied considerably among the patients. During the healing phase, the
      NO3 excretion decreased concurrently with improvement of symptoms and colorectal
      ulceration, but the NO2 excretion increased. During the inactive phase of the
      disease, the NO3 and NO2 excretions were significantly lower than during the
      active phase, and the NO2/NO3 ratio resembled that in the healthy controls. In
      contrast, a patient who failed to respond to treatment showed continuously high
      NO3 and NO2 excretion rates. These results indicate that urinary NO3 and NO2
      excretions vary with the disease state in ulcerative colitis.

PMID- 8739091
TI  - Pressure-cross-sectional area relations and elasticity in the rabbit oesophagus
      in vivo.
AB  - The aim was to assess the luminal cross-sectional area (CSA) and the passive
      elastic properties of the oesophageal body under luminal pressure loading in
      anaesthetized rabbits. Stepwise inflation of a luminal balloon, in which the CSA
      and pressure were measured by means of impedance planimetry and perfused low
      compliance manometry, provided the distension stimulus. The parameters of
      elasticity were computed from steady state values of these measurements. The
      steady state pressure-CSA and pressure-radius relations were nonlinear. At the
      lowest and highest luminal pressure load of 1 and 10 kPa, the steady state CSAs
      were 39 +/- 3 and 91 +/- 4 mm2, respectively. The circumferential tension-strain
      distribution was nonlinear and showed an exponential behaviour that fitted well
      to the function tension = a.e(b.strain). Differentiation of the function yielded
      the wall stiffness which also showed an exponential behaviour.

PMID- 8739092
TI  - Prevalence of Helicobacter pylori infection and chronic dyspeptic symptoms among
      immigrants from developing countries and people born in industrialized countries.
AB  - The relationship between Helicobacter pylori infection and chronic dyspepsia is
      controversial. To determine the effect of H. pylori infection on dyspeptic
      symptoms, we compared the prevalence of H. pylori infection in immigrants from
      developing countries and people born in industrialized countries. Upper abdominal
      symptoms were assessed by a questionnaire and H. pylori infection was determined
      with a 13C-urea breath test and serology. H. pylori infection was found in 63% of
      subjects from developing countries and 11% of subjects from industrialized
      countries. There was no difference in the prevalence of dyspeptic symptoms
      between the 2 groups. The lack of difference in chronic dyspeptic symptoms
      between the groups, despite a major difference in the H. pylori prevalence,
      suggests that H. pylori infection is not a major contributor to chronic
      dyspepsia.

PMID- 8739094
TI  - Increased gastric absorption of polyethylene glycols in atrophic gastritis.
AB  - Atrophic gastritis increases the risk of developing gastro-intestinal tumours. An
      impaired barrier function of the gastric mucosa could contribute to this risk.
      The absorption of polyethylene glycols (molecular weights 414-766), expressed as
      recovery in 6-hour urine, was studied both after oral and duodenal loads in
      patients with atrophic gastritis (n = 18) and compared with controls without
      gastritis (n = 9). The patients had a higher absorption after oral than after
      duodenal load for molecular weights 502-546. The differences in absorption after
      oral and duodenal loads were correlated with the severity of the atrophy in the
      antrum. No differences were found in the controls. Absorption after the duodenal
      load did not differ between the study groups. The increased gastric absorption of
      polyethylene glycols in patients with atrophic gastritis may be caused by a
      permeability disturbance of the gastric mucosa.

PMID- 8739093
TI  - Endoscopic assessment of the effects of dipyrone (metamizol) in comparison to
      paracetamol and placebo on the gastric and duodenal mucosa of healthy adult
      volunteers.
AB  - The potentially damaging gastric and duodenal effects of dipyrone, a nonnarcotic
      analgesic agent, were evaluated in three phases in comparison to placebo and
      paracetamol. Three groups of 12 healthy adult volunteers were treated in a double
      blind study, according to a cross-over, randomization sequence, using the double
      dummy technique, for two 15-day periods, with dipyrone 3 g/day and placebo (group
      I), dipyrone 1.5 g/day and placebo (group II), and dipyrone 1.5 g/day and
      paracetamol 1.5 g/day (group III). An esophagogastroduodenoscopy was performed at
      the beginning and end of each treatment period. In the first treatment group,
      grade-3 and 4 mucosal lesions were found after dipyrone administration (3 g/day)
      in 3 of 12 (25%) subjects (multiple antral erosions, gastric ulcer and duodenal
      ulcer, 1 case each), whereas grade-2 mucosal lesions (antral erosions) were
      detected in 1 of 12 cases (8%) after the corresponding placebo treatment. The
      difference between the two treatments, however, was not statistically significant
      (p > 0.05). Only in the gastric ulcer case were subjective symptoms reported
      (feeling of hunger). At the 1.5-g/day dose (groups II and III), dipyrone produced
      no gastroduodenal lesions, the endoscopic results showing no appreciable
      difference between dipyrone and either placebo (p = 0.54) or paracetamol (p =
      0.99). No subjective symptoms were reported in any of these subjects. Dipyrone,
      administered for 2 weeks, has effects on the gastric and duodenal mucosa
      comparable to those of paracetamol and placebo, though noticeable damage is
      detectable at a dosage of 3 g/day.

PMID- 8739095
TI  - Presence of prostaglandin EP4 receptor gene expression in a rat gastric mucosal
      cell line.
AB  - RGM-1 is an epithelial cell line established from gastric mucosa of adult Wistar
      rats. In this study, we characterized this newly established cell line by
      Northern blot analysis. We also investigated deoxyribonucleic acid (DNA)
      synthesis and hexosamine production in RGM-1 by PGE2. Northern blot analysis did
      not detect any transcript of proton pump, gastrin receptor, histidine
      decarboxylase, somatostatin and pepsinogen 1, indicating the absence of
      characteristics of parietal, ECL, D and chief cells in RGM-1 cells. However, this
      periodic acid-Schiff (PAS)-positive cell line expressed prostaglandin EP4
      receptor mRNA but not EP1 and EP3 receptor mRNAs. [3H]-thymidine incorporation
      into DNA of the cells was not increased by PGE2. In contrast, PGE2 increased
      hexosamine content in RGM-1 cells. These results suggest that RGM-1 may be a
      useful model of gastric mucosal cells and that PGE2 plays a role on mucin
      synthesis in RGM-1 cells possibly via EP4 receptors.

PMID- 8739096
TI  - Diethyldithiocarbamate, a superoxide dismutase inhibitor, reduces indomethacin
      induced gastric lesions in rats.
AB  - We examined the effect of diethyldithiocarbamate (DDC), the superoxide dismutase
      (SOD) inhibitor, on the development of gastric lesions induced by indomethacin in
      rats. Indomethacin (25 mg/kg) was given subcutaneously, and gastric acid
      secretion, motility, lipid peroxidation, vascular permeability, and
      myeloperoxidase as well as gastric lesions were measured. Indomethacin produced
      high-amplitude contractions of the stomach and caused hemorrhagic lesions in the
      corpus mucosa with significant increase in neutrophil-related processes such as
      myeloperoxidase activity, vascular permeability and lipid peroxidation. These
      changes caused by indomethacin were all significantly inhibited by prior
      administration of atropine (3 mg/kg s.c.). Pretreatment of the animals with DDC
      (75-1,000 mg/kg s.c.) prevented these lesions induced by indomethacin in the
      corpus mucosa in a dose-dependent manner (> 100 mg/kg), though at high doses (>
      750 mg/kg) some damage was found in both the antrum and duodenum. DDC showed a
      significant inhibition against the gastric mucosal SOD activity (> 400 mg/kg),
      yet potently suppressed the increase of lipid peroxidation, vascular
      permeability, and myeloperoxidase activity caused by indomethacin. DDC dose
      dependently (> 75 mg/kg) inhibited the enhancement of gastric motility caused by
      indomethacin and showed a weak antisecretory effect at high doses (> 750 mg/kg).
      These results showed that DDC reduced indomethacin-induced gastric lesions by
      suppressing gastric motility, despite inhibiting SOD activity. This study also
      indicates the prime importance of gastric hypercontraction in the pathogenesis of
      this lesion model and suggests that other events including the neutrophil-related
      processes may be secondary to gastric hypercontraction caused by indomethacin.

PMID- 8739097
TI  - Lipomas of the esophagus: a new case.
AB  - We present a new case of esophageal lipoma. The rarity of this tumor and its
      submucosal origin can create problems for the correct diagnosis. Symptoms, when
      present, are of mechanical origin (obstruction) with dysphagia. Treatment is
      endoscopic or surgical removal.

PMID- 8739098
TI  - Effect of 3'-untranslated region on expression of TNF alpha cDNA in Escherichia
      coli.
AB  - A construct pRL-rhTNF alpha 2, in which the 110 bp 3'-untranslated region of
      rhTNF alpha cDNA was deleted, was transformed in E.coli. The expression level of
      several positive transformants was determined. The results showed that the
      expression of pRL-TNF alpha 2 was stable and the biological characteristics of
      the protein product were the same as that of pRL-rhTNF alpha. Furthermore, the
      expression level of pRL-rhTNF alpha 2 was increased. It is suggested that the 3'
      untranslated region may have some effects on gene expression. A TA-rich sequence,
      TTTATTA, contained in the 3'-untranslated region of pRL-rhTNF alpha may be
      involved in the inhibitory effect on gene expression.

PMID- 8739099
TI  - Preparation of monoclonal antibodies specific for methyl esters of gibberellins
      A7 and A4.
AB  - According to the heterogeneity of the immunogen of GA3-3-O-HSA, which contained
      other components such as GA3-7-CONH-HSA, two kinds of monoclonal antibodies
      (MAbs) against different antigen determinants of GA3 were prepared in a single
      process using a two-step screening assay for hybridomas. The results from a cross
      reactivity experiment showed that MAb BG2 was specific for GA7/4 methyl esters
      (GA7/4me) with high affinity. Its affinity for GA7me was over 100 and 200 times
      higher than for GA3me and GA1me, respectively. Methylation of the 7-oic acid
      significantly increased the binding of MAb BG2 with GAs. On the contrary, the
      absence of a double bond or 3beta-OH in ring A and the breakdown of 19,10-gamma
      lactone as well as the presence of 13-OH in ring D greatly reduced the binding of
      MAb BG2 with GAs. This antibody with high specificity can be used effectively to
      quantify and localize the main active GA7 and GA4 from the early non
      hydroxylation pathway of GAs metabolism. Using this antibody, enzyme immunoassays
      with high sensitivity were developed which displayed linear ranges from 1.0 x 10(
      14) to 1.0 x 10(-12) mol for GA4me and from 2.0 x 10(-15) to 2.0 x 10(-13) mol
      for GA7me.

PMID- 8739100
TI  - Hairy root culture of Artemisia annua L. by Ri plasmid transformation and
      biosynthesis of artemisinin.
AB  - The hairy root culture system of the medical plant Artemisia annua L. was
      established by infection with Agrobacterium rhizogenes R1601. The transgenic
      state of transformed roots was confirmed by Southern blot hybridization with TL
      DNA of pFw302. The expression of NPTII gene was confirmed by enzymic assay. The
      important secondary metabolites-artemisinin was obtained in the hairy root
      culture. The effects of various physical and chemical factors on the growth of
      the hairy roots and production of artemisinin were studied. Artemisinin could be
      detected in hairy roots cultures in the light. The optimum pH value of the medium
      was 5.4. Fast growth of the hairy roots and maximal production of artemisinin was
      observed in the presence of 3% sucrose. Low concentration of naphthylacetic acid
      (0.025 mg/L) enhanced the growth of the roots but inhibited the production of
      artemisinin. The growth and artemisinin production in hairy root cultures were
      greatly promoted by the addition of gibberellin (GA3) to the medium. Its optimum
      concentration was 4.8 mg/L.

PMID- 8739101
TI  - Integration of glucoamylase gene from Aspergillus niger into Saccharomyces
      cerevisiae genome and its stable expression.
AB  - Starch digestible delta-integrants were constructed by integrative transformation
      of a linear YIP plasmid carrying Aspergillus niger glucoamylase cDNA under the
      control of the MF alpha 1 promoter and its prepro signal and the delta sequence
      of the Ty element from yeast. The integration of glucoamylase cDNA into
      Saccharomyces cerevisiae was identified by Southern analysis. The secreted
      glucoamylase activity of integrants in the medium with soluble starch as a carbon
      source reached 2.5 u/ml. After ten times of successive transfers in a
      nonselective medium, the activity of secreted glucoamylase of integrant was
      approximately at its original level.

PMID- 8739102
TI  - Oleyl oleate synthesis by immobilized lipase from Candida sp.1619.
AB  - The effect of 14 different lipases on oleyl oleate synthesis were compared. The
      lipase from Candida sp.1619 had the highest esterification activity. The lipase
      was immobilized by adsorbing it on celite with 0.1 (w/w) coconut oil, Tween 80,
      and 1% (w/w) MgSO4 as coimmobilizing agents. The initial esterification velocity
      of the immobilized lipase was 1.5 times faster than the one without co
      immobilized agents added. The optimum temperature for oleyl oleate synthesis was
      30 degrees C. The final esterification rates were over 90%, while the reaction
      temperature ranged from 0 degrees C to 60 degrees C. It attained 10.25%
      esterification activity even at 100 degrees C. The optimum pH for esterification
      was 6.0. By means of dehydration, the final esterification rate reached 99%.
      Among 23 kinds of organic solvents added, hydrophobic alkanes promoted
      esterification, especially isooctane, n-nonane, and n-hexane. In batch reaction,
      half-lives of the immobilized lipase was 990 hours at 28 degrees C. The
      esterification rate remained 78% after running in continuous-flow column reactor
      at 28 degrees C for 1,000 hours.

PMID- 8739103
TI  - Preparation and characterization of monoclonal antibodies against aflatoxin B1.
AB  - Five hybridoma cell lines producing monoclonal antibodies (MAb) against Aflatoxin
      B1 (AFB1) were established after fusion of mouse myeloma cells (SP-2/O-Ag-14)
      with spleen cells isolated from male BALB/c mice immunized with AFB1-BSA
      conjugate. Among these, one MAb, designated AFB1-2H8, was of the subtype IgG3 and
      the acidic fluid of which gave high dilution titers (1:5 x 10(5). The sensitivity
      of a competitive inhibition enzyme immunoassay (CIEIA) using AFB1-2H8 for AFB1
      demonstrated that the linear range was 0.5-50 ng/ml and the minimum detectable
      concentration of AFB1 was 0.01 ng/ml. The specificity of the MAb was determined
      and showed no significant crossreaction with any of the metabolites tested. So th
      - MAb and the CIEIA described may be useful in the detection of AFB1 in food and
      feed.

PMID- 8739104
TI  - Modeling of penicillin G hydrolysis to 6-APA in an immobilized enzyme-ion
      exchange system.
AB  - A composite system of an immobilized enzyme reactor combined with an ion exchange
      column was employed for hydrolysis of penicillin G to 6-APA with continuous
      removal of PAA. In this study, a mathematical model of penicillin G hydrolysis to
      6-APA in the composite system was developed based on the compartment model, the
      profile of concentration in the ion exchange column, and the enzyme kinetics in
      the immobilized enzyme reactor. After checking the simulation values and
      experimental data, the effects of the resin volume, the flow rate, and the
      switching time on the time required to reach the desired conversion rate was also
      examined by computer simulation.

PMID- 8739105
TI  - A simple method for the transformation of Agrobacterium tumefaciens by foreign
      DNA.
AB  - A method for successful introduction of Ti plasmid vector ( > 10 kb) into
      Agrobacterium tumefaciens is described. Competent A.tumefaciens cells were
      prepared with 50 mmol/L CaC1(2) at room temperature and introduction was done on
      ice followed by a 28 degrees C heat pulse. The efficiency of transformation was
      10(-4)-10(-5) transformants per total recipient population or 10(6) transformants
      per microgram DNA. The effects of growth phase of A. tumefaciens cells,
      concentration of CaC1(2) solution, temperature, liquid N2, heat pulse, recovery
      time, and storage time of competent cells at 4 degrees C or -20 degrees C (in 15%
      glycerin) on transformation were studied.

PMID- 8739106
TI  - Studies on high salt tolerance of transgenic tobacco.
AB  - With E. coli mtlD gene (encoding mannitol 1-phosphate dehydrogenase) and gutD
      gene (encoding glucitol 6-phosphate dehydrogenase) cloned, plant expression
      vector pBIGM had been obtained by inserting mtlD and gutD genes into binary
      vector pBin438. Tobacco was transformed with A. tumefaciens LBA4404 containing
      pBIGM. Results of molecular hybridization of transformed plants indicated that
      mtlD and gutD genes had integrated into the genomic DNA of tobacco plants.
      Experiments of salt tolerance and analysis of sugar alcohols showed that the
      accumulation of different sugar alcohols in transgenic tobacco plants had
      increased salt tolerance of tobacco.

PMID- 8739107
TI  - Cloning of a gene encoding the precursor of nisin by PCR.
AB  - The structural gene for the precursor of nisin was synthesized by polymerase
      chain reaction and then cloned in pUC18. The nucleotide sequence of the cloned
      precursor nisin gene was determined by dideoxy termination method. The sequence
      data obtained agreed with those of precursor nisin genes isolated by other
      workers from different Lactococcus lactis strains.

PMID- 8739108
TI  - Special issue. Anorexia Nervosa: Basic Mechanisms, Clinical Approaches and
      Treatment. Proceedings of a conference. Geneva, Switzerland, September 27-29,
      1993.

PMID- 8739109
TI  - Epidemiology of anorexia nervosa.
AB  - Findings of epidemiological studies of the rates, incidence, and prevalence of
      eating disorder over time and in different populations are reviewed. Risk factors
      for anorexia nervosa and bulimia nervosa are also addressed. Methodological
      recommendations for future directions in epidemiological studies of eating
      disorders are presented.

PMID- 8739110
TI  - Epidemiological data on anorexia nervosa in Japan.
AB  - An epidemiological survey on anorexia nervosa was performed in Japanese hospitals
      in 1985 and 1992 using a questionnaire. The reported number of patients with
      anorexia nervosa was 2391 from 732 institutions. From these data, the total
      number of anorexia nervosa patients treated in 1985 in Japanese hospitals was
      estimated to be about 3500-4500. In 1992, the reported number of patients with AN
      was 2247. The total number of AN patients treated in 1992 was estimated to be
      about 4500-4600, which is a little higher than that in 1985 (3500-4500). The
      prevalence was 3.6-4.5 per 100000 among the general population, 6.3-9.7 per 10(5)
      among the female population, and 25.2-30.7 per 10(5) among the 13-29 year-old
      female population.

PMID- 8739111
TI  - Clinical characteristics and course of anorexia nervosa in Latin America, a
      Brazilian sample.
AB  - The authors present the clinical description of a sample of anorexic patients
      from an eating disorder program from a non-English developing country. The
      patients were diagnosed according to DSM-III-R criteria and treated with a
      multidisciplinary approach. Similarities to and differences from other Western
      patient studies are discussed.

PMID- 8739112
TI  - The psychobiology of eating behavior in anorexia nervosa.
AB  - Two models for conceptualizing eating behavior are presented and the development
      of the experimental methodology to examine eating behavior is described in
      historical context. Specific studies of eating behavior in eating disorder
      patients are described with emphasis on how these studies examine aspects of the
      two hypothetical models that are presented on eating behavior. The studies
      present and focus on hunger and satiety perceptions, cognitive sets, and the
      neurotransmitter associated with satiety, serotonin. Unfortunately, no single
      investigation can encompass all of the variables that need to be measured that
      affect eating behavior. The studies described of both acutely ill and short-term
      recovered eating disorder patients indicate there may be some perceptual and
      physiological traits that are present in anorexia nervosa and bulimia nervosa.
      Studies over a longer period of time are needed to substantiate this. An eventual
      integrative explanation of disturbed eating behavior that is documented in eating
      disorder patients will be possible only after extensive investigations of the
      components.

PMID- 8739113
TI  - Studies of serotonin function in anorexia nervosa.
AB  - Neuroendocrine, temperature, test-meal, and psychometric responses are reviewed
      following challenges with the post-synaptic 5-HT receptor agonist m
      chlorophenylpiperazine (m-CPP), the 5-HT precursor L-tryptophan (L-TRP), and
      placebo in 12 patients with anorexia nervosa (AN) and 16 healthy controls. A
      subset of the AN patients (n = 8) were rechallenged 3-4 weeks after attaining a
      predetermined goal weight. AN patients had blunted prolactin (PRL) responses to
      both m-CPP and L-TRP at low-weight and at goal-weight in comparison to controls,
      although there was a tendency toward normalization with weight gain. There were
      trends for blunted growth hormone (GH) responses following both L-TRP and m-CPP
      in the low-weight but not the goal-weight AN patients. Cortisol (CORT) responses
      following m-CPP and L-TRP were not significantly different among any of the
      groups. Temperature and test-meal measures were largely unaffected by
      serotonergic agents in the patients, although m-CPP decreased meal size in the
      controls. Psychometric responses were variable and are briefly described. Taken
      together, these findings indicate that responsiveness in post-synaptic
      hypothalamic-pituitary serotonergic pathways is altered in AN patients. Although
      there were some trends toward normalization of responsiveness following goal
      weight attainment, many differences tended to persist in the patients despite an
      average increase of 13 kilograms. These may represent changes in serotonergic
      function at levels in the CNS "above" the hypothalamus.

PMID- 8739114
TI  - Central and peripheral noradrenalin regulation in eating disorders.
AB  - Norepinephrine and its metabolites were studied in various body fluids (plasma,
      urine and cerebrospinal fluid) of patients with anorexia nervosa, bulimia nervosa
      and healthy young women. The reaction of plasma norepinephrine to different
      stimuli like orthostatic challenge, test meals, standardized exercise, mental
      challenge tests etc. were studied. All results indicate a reduced noradrenergic
      activity in the central and peripheral nervous system of patients with eating
      disorders. The clinical consequences of these changes are hypotension,
      bradicardia, hypothermia and depression. Evidence is presented that the reduced
      activity of the sympathetic nervous system is caused by starvation (anorexia
      nervosa) or intermittent dieting (bulimia nervosa).

PMID- 8739115
TI  - Aspects of the neuroendocrine control of somatotropic function in calorically
      restricted dogs and patients with eating disorders: studies with cholinergic
      drugs.
AB  - A series of studies was devised in both an experimental model of food
      deprivation, i.e., beagle dogs undergoing a progressive reduction of calorie
      intake and adolescent females with anorexia nervosa (AN) in the acute and
      recovery phase, and in patients with atypical eating disorders. The studies were
      aimed at ascertaining whether the alleged function of the hypothalamic system
      inhibitory to growth hormone (GH) secretion, i.e., the somatostatinergic, may
      account for at least some of the abnormalities of GH secretion present in AN
      patients (e.g., elevated basal GH levels, paradoxical GH rise after glucose or
      thyrotropin releasing hormone, etc). Caloric restricted dogs or patients with
      eating disorders were given an intravenous injection of the physiologic GH
      releasing peptide GHRH alone or preceded by pirenzepine, a muscarinic cholinergic
      antagonist reportedly capable of eliciting hypothalamic release of somatostatin
      (SS), or pyridostigmine, a muscarinic cholinergic agonist which, conversely,
      would restrain hypothalamic release of SS. In addition, dogs were challenged with
      acute administration of glucose or thyrotropin-releasing hormone, compounds also
      thought to act via somatostatinergic influences. Data obtained in dogs under
      caloric restriction or in AN patients in the acute phase of the disease with
      drugs affecting cholinergic transmission suggest that the latter is increased in
      both conditions (only partial suppression of the GHRH-induced GH rise with
      pirenzepine, failure of pyridostigmine to further enhance the GH response to
      GHRH). Instead, in the same AN patients in the acute phase tested during
      recovery, in AN patients during the recovery phase, and in patients with atypical
      eating disorders, pirenzepine completely suppressed the GH response to GHRH, as
      it did in controls. Finally, data obtained on basal and GHRH-stimulated GH
      release in dogs given glucose or thyrotropin-releasing hormone and in AN patients
      given arginine, another compound thought to act via inhibition of
      somatostatinergic influences, do not support the view that somatostatinergic
      function is impaired in states of food deprivation.

PMID- 8739116
TI  - Neuropeptide abnormalities in anorexia nervosa.
AB  - Starvation-induced alterations of neuropeptide activity probably contribute to
      neuroendocrine dysfunctions in anorexia nervosa. For example, CRH alterations
      contribute to hypercortisolemia and NPY alterations may contribute to amenorrhea.
      Alterations of these peptides as well as opioids, vasopressin, and oxytocin
      activity could contribute to other characteristic psychophysiological
      disturbances, such as reduced feeding, in acutely ill anorexics. Such
      neuropeptide disturbances could contribute to the vicious cycle that has been
      hypothesized to occur in anorexia nervosa. That is, the consequences of
      malnutrition perpetuate pathological behavior.

PMID- 8739117
TI  - The hypothalamic-pituitary-adrenal axis in anorexia nervosa.
AB  - Studies examining the function of the hypothalamic-pituitary-adrenal (HPA) axis
      in anorexia nervosa are reviewed. A principal finding is that of
      hypercortisolism, associated with increased central corticotropin-releasing
      hormone levels and normal circulating levels of adrenocorticotropic hormone.
      Similarities between neuroendocrine findings in anorexia nervosa and in affective
      disorder are reviewed. The contribution of circadian rhythm disturbances and
      malnutrition to observed HPA axis abnormalities in anorexia nervosa is also
      considered. Directions for future research are discussed.

PMID- 8739118
TI  - Carbohydrate metabolism and its regulatory hormones in anorexia nervosa.
AB  - Findings of studies of carbohydrate metabolism in anorexia nervosa are reviewed.
      Topics covered included fasting blood sugar concentrations; serum insulin
      concentrations, insulin receptor binding activity, insulin sensitivity, and
      insulin resistance; plasma ketone bodies and free fatty acids; glucose tolerance
      tests; growth hormone, cortisol, intestinal hormones, and norepinephrine.
      Metabolic changes reported in anorexia nervosa are similar to those found in
      human and animal studies of states of caloric and carbohydrate restriction.
      Restoration of normal body weight is associated with normalization of virtually
      all measures. It is concluded that published studies offer no conclusive evidence
      for a syndrome-specific impairment in carbohydrate metabolism in anorexia
      nervosa.

PMID- 8739119
TI  - Immunoendocrine aspects of anorexia nervosa.
AB  - The T-lymphocyte proliferative response to phytohemoagglutinin (PHA) stimulation
      was the same in 11 anorexic women, 6 restricted (AN-R) and 5 bulimic (AN-B), and
      in 11 sex- and age-matched controls, in basal conditions and after acute
      administration of corticotropin-releasing hormone (CRH). Basal plasma levels of
      ACTH and cortisol were higher in patients than in controls, while beta-endorphin
      (beta-EP), growth hormone (GH) and prolactin (PRL) concentrations did not differ
      in the two groups. ACTH and beta-EP responses to CRH stimulation were blunted in
      patients, while those of cortisol did not differ in the two groups. ACTH, beta-EP
      and cortisol responses to the dexamethasone suppression test were impaired in 55%
      of the patients. Baseline T-lymphocyte concentrations of cholecystokinin-8 (CCK
      8) and beta-EP were measured in another group of 56 anorexics, 33 restricted and
      23 bulimic, and in 24 controls. CCK-8 values were significantly lower and beta-EP
      values significantly higher in patients than in controls.

PMID- 8739120
TI  - Neuroimaging in anorexia nervosa.
AB  - Neuroimaging in anorexia nervosa has revealed morphological and functional
      alterations, most of which are currently interpreted as consequences of the
      anorectic state that are reversible, at least partially, after weight gain.
      Enlargement of CSF spaces, mainly of cortical sulci, is evident on CT and MRI.
      This reversible shrinkage of brain tissue ("pseudoatrophy") also affects the
      pituitary gland. A functional imaging study with positron emission tomography
      (PET) revealed caudate hyperactivity during the anorectic state, and several mild
      right-left asymmetries possibly related to alterations of mental state
      (vigilance, depression, etc.) have also been reported in bulimia nervosa. New
      aspects may be added, when techniques to image functional brain activation during
      specific tasks and regional receptor binding capacities are used to study
      anorexia nervosa.

PMID- 8739121
TI  - Differential sensitivity of various temporal lobe structures in the rat to
      kindling and status epilepticus induction.
AB  - Using focal brain stimulation (kindling), discrete seizures can be triggered from
      many neuroanatomic sites with varying degrees of facility. From several of these
      sites, protracted seizures or status epilepticus (SE) also can be triggered. To
      date, no comparison has been made between different brain sites in their
      sensitivity both to kindling and to SE development. In this report, we have
      compared the kindling profiles of three amygdala nuclei, namely the basal (BL),
      central (CE), and medial (ME) nuclei, to the adjacent piriform (PIR) and
      perirhinal (PRH) cortices. In addition, three weeks following kindling, the
      susceptibility of each kindled site to status epilepticus (SE) was assessed by
      exposing the site to 60 min of electrical stimulation. We observed that (a)
      during the course of daily kindling, the afterdischarge threshold dropped
      progressively and significantly in all structures, (b) the rate of kindling in
      the PRH and PIR cortices and the CE amygdala was significantly faster than either
      the BL or ME amygdala, (c) when discrete convulsions were triggered, the latency
      to forelimb clonus in the PRH cortex and CE amygdala was significantly shorter
      than the other three structures, and (d) despite being slower to kindle than most
      other sites, stimulation of the BL nucleus most readily triggered SE. The
      kindling data suggest that discharges triggered from the PRH and CE more readily
      access motor systems supporting limbic convulsions than discharges triggered from
      the BL, ME nuclei or the PIR cortex. On the other hand, the SE data indicate that
      the mechanisms and circuits associated with the development of discrete kindled
      seizures are not identical to those associated with the induction of limbic SE.

PMID- 8739122
TI  - Flurothyl seizure susceptibility in rats following prenatal methylazoxymethanol
      treatment.
AB  - Methylazoxymethanol acetate (MAMac) is a potent teratogenic agent which can
      produce ectopic cell placement in developing rat brains. In the present study, we
      evaluated (i) whether prenatal exposure to MAMac results in a lowered seizure
      threshold to flurothyl and (ii) if there is a correlation between the number of
      ectopic cells in MAMac-exposed hippocampus and flurothyl-induced seizure latency.
      In 60 day old (P60) rats exposed to MAMac in utero, the latencies to myoclonic
      jerk (173 +/- 2.3 s) and forelimb clonus (215 +/- 4.6 s) were significantly
      shorter than those of controls (200 +/- 6.9 s and 238 +/- 8.8 s, respectively).
      MAMac also increased the proportion of flurothyl-treated rats that progressed
      from bilateral forelimb clonus to generalized tonic-clonic seizures (control:
      33%; MAMac: 91%). Shorter seizure latencies were associated with an increased
      number of ectopic pyramidal cells in region CA1/CA2. These results suggest
      seizure susceptibility is enhanced in an animal model (MAMac) characterized by
      abnormal neuronal migration.

PMID- 8739124
TI  - D-23129: a new anticonvulsant with a broad spectrum activity in animal models of
      epileptic seizures.
AB  - The anticonvulsant activity of the novel drug D-23129 (N-(2-amino-4-(4
      fluorobenzylamino)phenyl)carbamic acid ethyl ester) was evaluated in animal
      models of epileptic seizures. D-23129 was active after oral and intraperitoneal
      administration in rats and mice in a range of anticonvulsant tests at nontoxic
      doses. The compound was active against electrically induced seizures (MES, ED50
      rat p.o. = 2.87 mg/kg), against seizures induced chemically by pentylenetetrazole
      (s.c. PTZ, ED50 mouse p.o. = 13.5 mg/kg), picrotoxin and N-methyl-D-aspartate
      (NMDA) and in a genetic animal model, the DBA/2 mouse. It was not active against
      seizures induced by bicuculline and strychnine. Motor impairment, evaluated with
      the rotarod test and by observation in the open field, was minimal at doses
      showing anticonvulsant activity. D-23129 was very effective in elevating the
      threshold for electrically and chemically induced seizures. Considering the dose
      increasing the MES threshold by 50% (TID50 mouse i.p. = 1.6 mg/kg; TID50 rat i.p.
      = 0.72 mg/kg) and the TD50 obtained in the rotarod test, the protective index of
      D-23129 is better than that of valproate and phenytoin. During 14 days chronic
      oral treatment with 15 mg/kg, no development of tolerance was observed. D-23129
      thus presents an orally active, safe, broad spectrum anticonvulsant agent, which
      is structurally unrelated to anticonvulsants currently used. We expect that D
      23129 will improve the treatment of refractory seizures in humans.

PMID- 8739123
TI  - Audiogenic seizures following global ischemia induced by chest compression in
      Long-Evans rats.
AB  - Transient global ischemia was used to produce a rat model of generalized tonic
      clonic epilepsy. Controlled chest compression in ketamine-anesthesized Long-Evans
      rats produced transient global ischemia by mechanically preventing the heart from
      pumping blood. Circulation was restored by standard cardiopulmonary resuscitation
      techniques. With a temporal muscle (skull) temperature of 35 +/- 0.4 degrees C,
      75% (76/102) of the rats survived 7 min of chest compression. Generalized
      seizures could be evoked in 78% (59/76) of the surviving rats by a 60 s exposure
      to a loud sound (bell, 110 dB) beginning 24 h after the ischemic episode. The
      seizure patterns seen resembled those described by Maresceaux (1987) for
      genetically seizure-prone Wistar rats. Susceptibility to sound-induced seizures
      declined with time, with wide variations in recovery rate between individuals;
      one rat showed a daily sound-induced seizure for over 5 months. Seizures were
      attenuated or blocked by treatment with carbamazepine or sodium valproate. This
      model is similar to the great vessel occlusion model used by Kawai et al. (1995),
      but is less invasive. We believe it will be useful in the evaluation of therapies
      for acquired generalized (grand mal) seizures.

PMID- 8739125
TI  - Effects of chronic morphine pretreatment on amygdaloid kindling development,
      postictal seizure and suppression and benzodiazepine receptor binding in rats.
AB  - Effects of chronic morphine pretreatment on the development of amygdaloid
      kindling, seizure suppression and benzodiazepine (BDZ) receptor binding in rats
      were evaluated. The morphine-pretreated animals showed faster acquisition of
      seizure activity. Further evaluation of the postictal seizure suppression
      immediately after a fully kindled seizure demonstrated that morphine-pretreated
      rats had a decreased sensitivity to subsequent kindling stimulations. Twenty-four
      hours after the last electrical stimulation, saline-pretreated fully kindled rats
      showed enhanced BDZ receptor binding in dentate gyrus, and decreased binding in
      cingulate cortex ipsilateral to the stimulation site, compared to saline
      controls. Morphine-pretreated amygdala-kindled rats had significantly higher BDZ
      binding in piriform, entorhinal and sensorimotor cortices, basolateral and
      cortical amygdaloid nuclei, dentate gyrus, CAI-3 areas, substantia nigra pars
      reticulata and periaqueductal gray. The present study indicates that the previous
      experience with chronic morphine modifies the kindling process and that the
      enhanced BDZ receptor binding detected in our experiments may be involved in the
      enhanced postictal seizure suppression observed in these animals.

PMID- 8739126
TI  - Exclusion of linkage between idiopathic generalized epilepsies and the GABAA
      receptor alpha 1 and gamma 2 subunit gene cluster on chromosome 5.
AB  - Hereditary factors play a major role in the etiology of idiopathic generalized
      epilepsies (IGEs). The pivotal function of ionotropic gamma-aminobutyric acid
      type A receptors (GABRs) in inhibitory neurotransmission in the mammalian central
      nervous system suggests that they may be involved in epileptogenesis and genetic
      predisposition to IGEs. Dinucleotide repeat polymorphisms associated with the
      human GABAA receptor alpha 1 (GABRA1) and gamma 2 subunit (GABRG2) gene cluster
      on chromosome 5q32-q35 offer the opportunity to test whether these candidate
      genes confer susceptibility to IGEs. Our linkage analyses in 63 families
      ascertained through IGE patients with either juvenile myoclonic epilepsy,
      juvenile absence epilepsy or childhood absence epilepsy do not support the
      hypothesis that variants within the GABRA1 and GABRG2 gene cluster contribute a
      frequent major gene effect to the expression of the common familial IGEs.

PMID- 8739127
TI  - Significance of head turn sequences in temporal lobe onset seizures.
AB  - We studied head turning in 239 complex partial seizures with or without
      generalization, in 32 patients with unilateral temporal lobe epilepsy. Head turns
      occurred in 73% of seizures that did not evolve to focal jerking or secondary
      generalization, and in all 41 seizures that secondarily generalized. In seizures
      without focal jerking or secondary generalization the most common pattern was
      that of single head turns (70%) which were ipsilateral to the focus in 94%. The
      next most common pattern was that of two or more head turns, with the first two
      turns in the same direction (19%), always ipsilateral to the focus. In seizures
      with secondary generalization, the most common sequence was that of two head
      turns contralateral to each other (59% of seizures). The first was always
      ipsilateral to the focus, associated with dystonic posturing in 96%, and was not
      tonic in character. The second was always contralateral, was tonic in character,
      and was still present within five seconds of secondary generalization or focal
      jerking. Our results suggest different patterns and sequences of head turning
      temporal lobe complex partial seizures without, and those with focal jerking or
      secondary generalization. Some sequences have powerful lateralizing value that
      can complement other lateralizing features.

PMID- 8739128
TI  - Gelation of fractionated canine submaxillary mucin in a chaotropic solvent.
AB  - Rheological measurements have been performed on three molecular weight fractions
      of purified canine submaxillary mucin (CSM) dissolved in the chaotropic solvent 6
      M guanidine hydrochloride (GdnHCI). Solutions of the lower molecular weight
      fractions are viscoelastic sols, and their dynamic moduli can be scaled with
      respect to molecular weight and concentration according to linear viscoelasticity
      theory. In contrast, preparations of the highest molecular weight fraction form
      viscoelastic gels that exhibit an equilibrium shear modulus, Ge', which scales
      with mucin concentration as Ge' approximately c3. Amino acid and carbohydrate
      analyses of all three fractions are similar; thus, the differences in rheological
      behavior are attributed to molecular weight differences, which affect the degree
      of coil overlap in solutions of a given concentration. These observations
      demonstrate conclusively that mucin glycoproteins of high molecular weight form
      gels under conditions in which the mucin chains physically interpenetrate, even
      when non-covalent intermolecular interactions are extensively disrupted. A
      comparison of these results with previous studies of purified submaxillary and
      tracheobronchial mucins indicates that the carbohydrate side-chain length, in
      addition to molecular weight, is an important determinant of the observed elastic
      response and the ability to form physical gels.

PMID- 8739129
TI  - Thermal stability of Artemia HGPRT: effect of substrates on inactivation
      kinetics.
AB  - Hypoxanthine-guanine phosphoribosyltransferase (HGPRT, E.C.2.4.2.8) from Artemia
      cysts exhibits maximum activity at 70 degrees C. Its thermal stability has been
      examined following enzymatic activity as a function of temperature. Cold-induced
      renaturation experiments of samples heated at increasing temperatures showed that
      reversibility of thermal inactivation depends on the incubation time and final
      temperature. Prolonged incubation of the thermoinactivated enzyme at 0 degree C
      did not afford any further increase of the catalytic activity at 37 degrees C.
      The complex substrate PRPP:Mg protects HGPRT from thermal inactivation. However,
      incubations with hypoxanthine rendered a less thermostable enzyme at any
      temperature tested. The irreversible inactivation of HGPRT proceeds in two
      exponential steps. The analysis of the apparent rate constants for the fast and
      the slow phases, lambda 1 and lambda 2 as per the Lumry and Eyring model suggests
      the existence of more than three states in the thermal denaturation pathway of
      the free enzyme. In the presence of PRPP:Mg the irreversible process follows a
      single exponential and proceeds very slowly below 70 degrees C. PRPP:Mg also
      protects the enzyme from inactivation by NEM and pCMB, suggesting that -SH groups
      may be in the vicinity of the active site.

PMID- 8739130
TI  - Computational study of the conformational profiles of model bis-cystine cyclic
      peptides.
AB  - Bis-cystine cyclic peptides are a new kind of molecules with potential use as
      cavitands, transporters or antagonists of target ligands. Studies aimed at
      establishing their conformational profiles may prove useful in understanding
      their characteristics and potentiate their use in molecular design. The present
      investigation reports the results of a computational study devoted to
      establishing the conformational preferences of model bis-cystine cyclic peptides
      and the properties in common with their linear analogs. For this purpose a study
      of four model compounds: (Ac-Cys-X-Cys-NHMe)2 and (Ac-Cys-X-X-Cys-NHMe)2 with X =
      Ala, Val, was performed. The goal of the study was to explore the importance of
      the conformational nature of the central residues, the effect of the number of
      them, and the loss of conformational freedom after cyclization on model
      molecules. Accordingly, the conformational space and the dynamic behaviour of the
      four cyclic peptides as well as the corresponding linear analogs was carefully
      explored. The results indicate the existence of structural patterns that might be
      useful for the use of this kind of molecule in de novo molecular design.

PMID- 8739131
TI  - Pressure-induced change in proteins studied through chemical modifications.
AB  - Pressure-induced change of two bovine proteins, alpha-lactalbumin (LA) and beta
      lactoglobulin (LG), was investigated at neutral pH by means of fluorescence and
      CD spectroscopy. The rate and the extent of modification was considerably
      increased by applying high pressure during the dansylation reaction of LG, while
      those for LA were only moderately affected. This difference was accounted for by
      the structural deformation of these proteins under high pressure. The
      fluorescence spectrum of these proteins measured under elevated pressure, as well
      as their fluorescence and CD spectra after the pressure release, indicated
      different responses towards pressure. The structural change of LA was practically
      reversible up to 400 MPa, whereas that of LG lost reversibility at 150 MPa or
      lower. Fluorescent measurement of dansylated (prepared at atmospheric pressure)
      proteins, especially the energy transfer from the intrinsic Trp residue to the
      dansyl group, showed that the protein structure was deformed by pressure and that
      the energy transfer facility of the two proteins was differently affected by high
      pressure, probably reflecting the degree of compactness of their pressure
      perturbed structures.

PMID- 8739132
TI  - Characterisation of sorbed water molecules on neutral and ionic polysaccharides.
AB  - Ionic and neutral polysaccharides with well-defined structures were chosen to
      investigate the mechanism of water sorption at different relative humidities.
      From an experimental point of view, the freezing water was determined by DSC when
      the total sorbed water was obtained from thermogravimetry. The isotherms of
      sorption and enthalpies of interaction were determined using the combination of a
      microbalance and a microcalorimeter. It is shown that freezing water appears for
      P/P(zero) > 0.85 especially with the neutral polymers. The differential molar
      enthalpy of interaction is higher for P/P(zero) < 0.85 corresponding to the
      fixation of two water molecules forming double H-bonds; this result is confirmed
      by molecular modelling; saturation is obtained experimentally for 4 water
      molecules interacting per glucose unit. On ionic polymers, the water retention
      increases especially over P/P(zero) approximately 0.8 and the enthalpy of
      interaction is higher for the first water molecules sorbed. For P/P(zero)
      approximately equal to 0.8, the numbers of bound water molecules found are 2 per
      glucopyranosyl unit for neutral polysaccharides, 5 for glucuronan and 9-10 for
      carboxymethylcellulose (CMC) of DS = 2 and hyaluronan (HA).

PMID- 8739133
TI  - Quercetin and DNA in solution: analysis of the dynamics of their interaction with
      a linear dichroism study.
AB  - Flow-Linear Dichroism (LD) spectra on quercetin-DNA solutions (buffer-ethanol
      30%) showed evidence that the flavonol can intercalate the biopolymer. There is
      no electrostatic component in the formation of the quercetin-DNA complex. The DNA
      concentration and the planarity of the chromophore are limiting factors in the
      interaction. There are no induced LD signals for concentrations of the biopolymer
      less than 7.8 x 10(-3) M phosphate. The interaction is most probably of a
      hydrophobic nature between the most hydrophobic segment of the quercetin
      (benzopyran-4-one) and the intercalation site, which allows the chromophore to
      penetrate the DNA helix and to arrange its planar structure more or less parallel
      to the adjacent planes of the nitrogenous bases. A comparison between the planar
      and hydrophobic flavonol quercetin, and the non-planar and hydrophilic flavanone
      dihydroquercetin, showed that the interaction of the latter with DNA was strongly
      limited. The notable biological activity of the quercetin compared to the
      'weaker' activity of the dihydroquercetin could also be derived from the
      different planarity (and probably hydrophobicity) of the two flavonoids. The very
      low concentration of the quercetin-DNA complex was efficiently shown by the high
      sensitivity of the LD technique, whereas it could not be resolved by isotropic UV
      Vis and induced circular dichroism spectra. The hypothesis of a frame shift
      mutagenicity activity of quercetin (Science 1977; 197: 577-578) is highly
      improbable. In fact, the affinity of quercetin for DNA, which emerges from this
      study, is very low compared with that of a typical intercalator agent (Q. Rev.
      Biophys. I 1992; 25: 51-170).

PMID- 8739134
TI  - Maillard induced complexes of bovine serum albumin--a dilute solution study.
AB  - Association of bovine serum albumin (BSA) on heating in the presence and absence
      of 2% xylose has been studied using dynamic light scattering and sedimentation
      velocity. When 3% solutions of the protein alone are heated at 95 degrees C
      association products are formed with molar masses of approximately 2 x 10(6)
      g/mol, a value which is independent of the time of heating. These aggregates can
      be dissociated in solvents that disrupt non-covalent bonds. When the reducing
      sugar xylose is present there is a continuous change in the hydrodynamic
      properties with time. After 80 min a molar mass in excess of 7 x 10(6) g/mol is
      obtained. This increase in molar mass is attributed to additional non-disulphide
      linkages resulting from the Maillard reaction. Information about the gross
      conformation of the Maillard induced association products has been obtained from
      MHKS (Mark-Houwink-Kuhn-Sakarada) double logarithmic plots of D20,w and S20,w
      against molar mass. The values of the MHKS coefficients obtained are most
      consistent with a linear rod: i.e. the association is of an end-to-end type.

PMID- 8739136
TI  - Some novel N-fatty acyl derivatives of a microbial galactosaminan.
AB  - Novel seven N-fatty acyl derivatives (degree of substitution 0.78-0.96) of a
      microbial galactosaminan were prepared in 59-79% yields by its reaction with
      fatty acid anhydrides in aqueous acetic acid-methanol. N-Acetyl and N-propionyl
      derivatives were soluble in water, aqueous 2% sodium hydroxide, and aqueous 2%
      acetic acid, but N-higher fatty acyl (> C6) derivatives were insoluble. Gel was
      not formed in these reactions.

PMID- 8739135
TI  - Thermal denaturation of an all beta-sheet protein--identification of a stable
      partially structured intermediate at high temperature.
AB  - The thermal unfolding of an all beta-sheet protein, cardiotoxin analogue III,
      from the Taiwan Cobra (Naja naja atra) is studied at pH 2.0, 4.0 and 6.0. At pH
      4.0, using circular dichroism and 1-anilino naphthalene-8-sulphonic acid (ANS)
      fluorescence binding studies, a stable partially structured intermediate is
      detected at 90 degrees C.

PMID- 8739137
TI  - Attitudes towards financing of dental care in a Swedish population.
AB  - The aim of the present study was to describe attitudes towards financing of
      dental care and to investigate the importance of different background factors for
      these attitudes. A questionnaire was sent to a random sample of 3000 persons aged
      45-69 years, living in Orebo County, Sweden, with 79.4% response. In the
      questionnaire the respondents indicated their agreement with four statements on
      issues concerning financing of dental care, using visual analogue scales. After
      the answers had been dichotomized, 45% agreed that "all dental care should be
      free of charge', 32% agreed that "all dental care should be provided by the
      county', 46% agreed that "it is more important to use resources on heart
      transplants than on dental care', and 43% agreed that "no public reimbursement
      should be given to cosmetic dental care'. The attitudes were associated with the
      following background factors: gender, age, marital status, place of residence,
      education, socioeconomic status, dental care system, dentist of choice, time
      since last dentist contact, and attitudes toward dental appearance and dental
      function. Different background factors were associated with each of the four
      different attitudes, and only educational level seemed to covary with all four
      attitudes. It is concluded that attitudes towards financing of dental care varied
      considerably within this population and that the different attitudes could be
      related to different background factors.

PMID- 8739138
TI  - Effect of treatment of palatal inflammatory papillary hyperplasia with local and
      systemic antifungal agents accompanied by renewal of complete dentures.
AB  - The aim of this study was to estimate the effect of local and systemic antifungal
      treatment, accompanied by renewal of complete dentures, on palatal inflammatory
      papillary hyperplasia (PIPH). The treatment groups consisted of 26 subjects
      treated with a local antifungal agent (miconazole, 2% gel) for 4 weeks and 13
      subjects treated with a systemic antifungal agent (fluconazole, 50 mg) for 2
      weeks (test groups). Ten subjects fitted with new complete dentures served as a
      control group. Variables examined before antifungal and prosthetic treatment
      included estimation of the size and color of the affected palatal area,
      measurements of the lengths of the papillae, and salivary variables. Six months
      after the completion of prosthetic treatment healing was determined as
      disappearance or marked reduction of the redness of the PIPH. Healing was more
      often observed in test groups (64%) than in the control group (20%) (p = 0.012).
      Fifty-eight per cent of the subjects treated with a local (miconazole, 2%) and
      77% of those treated with a systemic (fluconazole, 50 mg) antifungal agent were
      healed. Even though papillary hyperplastic tissue did not disappear, the
      treatment of PIPH with an antifungal agent without surgery before renewal of
      dentures might be an alternative treatment in mild cases.

PMID- 8739139
TI  - High strontium addition to chlorhexidine-fluoride gel does not increase its
      caries-preventive effect in rats.
AB  - One hundred Osborne-Mendel rats were weaned at the age of 21 to 22 days,
      inoculated with Streptococcus mutans in the mouth, and fed a semisynthetic diet
      for the next 43 days. The control group received no treatment. The study groups
      received gel applications on their molars with placebo, chlorhexidine-fluoride
      (CXF), CXF plus 50 ppm Sr, or CXF plus 250 ppm Sr daily for the first 21 days of
      the experiment Although caries was significantly reduced by CXF and CXF plus 50
      ppm Sr treatments, the Sr additive did not significantly improve the caries
      preventive effect of CXF. The addition of 250 ppm Sr to the CXF gel seemed
      markedly to weaken the effect of CXF.

PMID- 8739140
TI  - Life-style survey of patients with oral lichenoid reactions.
AB  - The occurrence of different life-style patterns, including marital status,
      educational level, nutrition, tobacco and alcohol use, and frequency of physical
      activity, in patients with oral lichenoid reactions (OLR) in total or partial
      contact with amalgam fillings was examined. When compared with an age- and sex
      matched control group, the daily intake of carbohydrates, fibers, and iron was
      statistically significantly higher in the OLR patients. Regarding marital status,
      there was a statistically significant difference between the OLR patients and the
      control subjects, the former group containing more people who were divorced or
      whose spouse had died. The frequency of physical activity was also statistically
      significantly higher in the OLR patients than in the control group. Hypothetical
      mechanisms that may lie behind the results obtained are discussed.

PMID- 8739141
TI  - Orthodontically induced root resorption in rat molars after 1-hydroxyethylidene
      1,1-bisphosphonate injection.
AB  - A single injection of 1-hydroxyethylidene-1, 1-bisphosphonate inhibits the
      formation of acellular cementum in rat molars. Instead, an atypical hyperplastic
      cementum is formed. In this study the resistance of this cementum to resorption
      was tested by applying an orthodontic force. It was found that roots lacking
      acellular cementum were readily resorbed. The readiness with which the atypical
      hyperplastic cementum was resorbed without any increase in multinucleated
      osteoblasts may offer useful opportunities to study the different phases of hard
      tissue resorption.

PMID- 8739142
TI  - Axial wall convergence of full veneer crown preparations. Documented for dental
      students and general practitioners.
AB  - The convergence angle in 478 full crown preparations was assessed. Of these
      preparations, 351 had been performed by general practitioners and 127 by dental
      students. Groups of preparations performed on incisors, premolars, and molars
      were compared, as were preparations performed by dentists and students. Two
      different convergence angles were measured for each tooth, buccolingually and
      mesiodistally. The results showed a mean angle of 21 degrees. The mean values for
      premolars and molars differed significantly. When a comparison was made of
      preparations performed by students, a significant difference was found between
      premolars and molars. The same comparison for general practitioners showed a
      significant difference both for incisors compared with molars and for premolars
      compared with molars. A wide range was found for the convergence of the axial
      walls, especially for the preparations performed by general practitioners.

PMID- 8739143
TI  - Assessment of single risk indicators in relation to caries increment in
      adolescents.
AB  - Base-line data on a series of risk indicators were related to 11-month caries
      increment in 181 subjects with a mean age of 13 years and 3 months. A caries
      increment equalling or exceeding one tooth surface was recorded in 21% of the
      subjects. The risk indicators consisted of past caries experience, white spot
      lesions, visible plaque and gingivitis, and six salivary tests: secretion rate,
      buffer effect, sucrase, mutans streptococci, lactobacilli, and Candida.
      Significant associations between caries increment and past caries experience (p =
      0.002), white spot lesions (p = 0.01), lactobacilli (p = 0.02), Candida (p =
      0.006), and sucrase (p = 0.02) were observed. The ensuing odds ratios were thus
      recorded: past caries experience, 3.6; white spot lesions, 2.9; salivary sucrase
      activity, 2.9; lactobacilli, 2.5; and Candida, 2.8.

PMID- 8739144
TI  - Multifactorial modeling for prediction of caries increment in adolescents.
AB  - The purpose of the study was to develop a multifactorial model for the prediction
      of 11-month caries increment in adolescents. The mean age of the subjects (n =
      181) at the base-line examination was 13 years and 3 months. The risk indicators
      consisted of past caries experience, white spot lesions, visible plaque,
      gingivitis, salivary secretion rate, buffer effect, sucrase, mutans streptococci,
      lactobacilli, and Candida. The multifactorial modeling included all the above
      risk indicators, age, and gender and resulted in different models in boys and
      girls, indicating the difficulty of caries prediction in adolescents. When boys
      and girls were combined, the final model included past caries experience,
      Candida, and salivary sucrase. Although the accuracy of the model was slightly
      below the 80% level recommended for screening purposes, the results provide
      clinically valuable information. The risk of caries increases with an increasing
      number of positive tests within the model.

PMID- 8739146
TI  - The prevalence of malocclusion in 13- to 15-year-old children in Nairobi, Kenya.
AB  - Data on occlusal features and the need for orthodontic treatment in Kenya is
      scanty. This study was carried out to determine the prevalence of malocclusion in
      children in Nairobi, Kenya. Nine hundred and nineteen children aged 13-15 years
      (468 male, 451 female) were examined. The registration method used was that
      described by Bjork et al. The prevalence of malocclusion was 72%. The predominant
      anteroposterior relationship of the dental arches was neutral occlusion (93%).
      Specific malocclusion traits were highest for crowding (19%), rotations (19%),
      posterior crossbite (10%), maxillary overjet (10%), and frontal open bite (8%).
      There was no statistically significant difference in the overall prevalence of
      malocclusion between males and females, but some occlusal traits were
      significantly higher in males. Although the findings indicate that the present
      population is not characterized by a substantial difference in the overall
      prevalence of malocclusion compared with other communities, some traits differed
      in prevalence from those reported elsewhere.

PMID- 8739145
TI  - Effect of palatal plate therapy in children with Down syndrome. A 1-year study.
AB  - The effect of palatal plate therapy on oral dysfunction in children with Down
      syndrome was studied during a 1-year period. Twenty-nine subjects with a mean age
      of 24 months were randomized to a test group or to a control group. The variables
      concerning orofacial muscle function--that is, "closed mouth', "tip of the tongue
      visible', "open mouth', "inactive protrusion of the tongue', and "active
      protrusion of the tongue'--were monitored by video recordings. After 12 months of
      therapy the mean duration of the factor "closed mouth' was significantly longer
      (p < 0.001) and "inactive protrusion of the tongue' significantly shorter (p <
      0.001) in the test group than in the control group. The results indicate that in
      children with Down syndrome, palatal plate therapy may be a valuable complement
      to a training program for improving orofacial muscle function.

PMID- 8739147
TI  - Analysis of caries-related factors in infants and toddlers living in Sweden.
AB  - The aims of this study were 1) to investigate whether oral hygiene and dietary
      habits established at 1 year of age are maintained at 2 years of age and 2) to
      analyze caries-related factors with regard to oral health between the age of 1
      and 3 years by using the salutogenic theory-that is, focusing on behavioral
      factors that do not result in impairment of health. Altogether 289 children were
      examined at 1, 2, and 3 years of age, and their parents were interviewed about
      the children's oral hygiene and dietary habits at 1 and 2 years of age. The
      result shows that caries-related habits, such as oral hygiene and dietary habits,
      established during infancy are maintained throughout early childhood. The
      principles of the salutogenic theory were found to be applicable when studying
      caries-related habits and oral health. Thus, if a dietary risk behavior is
      established at 1 year of age, the chance of remaining caries-free until 3 years
      of age is highest if good oral hygiene habits, including the use of fluoride
      toothpaste, are present at 2 years of age. We therefore conclude that
      comprehensive knowledge of a child's future dental health can be obtained by
      using chairside information-that is, interview of the parents and clinical
      examination of the children.

PMID- 8739148
TI  - Differences in biologic response of the mandibular condyle to forward traction or
      opening of the mandible. An experimental study in the rat.
AB  - The effect of different mandibular postures on the growth of the mandible was
      studied. A total of 60 female Wistar rats were divided into 3 groups, and all the
      animals were anesthetized for 6 h daily from the age of 30 days onwards. The
      first group served as controls. The second had the mandible maintained in a
      protracted position, and the third had the mandible in an open position during
      the anesthesia. Macroscopic measurements showed the growth of the mandibular
      condyle to be increased in a posteroinferior direction and also in a superior
      direction in the animals with the mandible in an open position. The cartilage
      layer containing collagen type II was significantly thinned, whereas cell
      proliferation had significantly increased in the posterosuperior region. In
      association with mandibular protrusion the thickness of the cell layer containing
      collagen type II had increased, and cell proliferation in the posterosuperior
      region had significantly decreased. Significant differences in the growth of the
      condylar process were observed histologically and histochemically between the
      experimental animals, implying that the most rewarding aspect of the regulation
      of condylar growth seems to be the possibility to regulate the maturation rate of
      the cartilage cells.

PMID- 8739149
TI  - Loss of myelin basic protein cationicity in DM20 transgenic mice is dosage
      dependent.
AB  - Demyelination in the transgenic mice depended on the dosage of the cDNA for DM20,
      in which low copy numbers (two to four and 17 copies of the minigene) showed no
      signs of demyelination. However when transgenic mice with 17 copies were made
      homozygous with 34 copies of the DM20 minigene (ND3A hm.) demyelination was
      observed at around 12 to 16 months compared with ND4 mice having 70 copies of the
      transgene which had an earlier onset of demyelinating symptoms at 3 months,
      demonstrating a transgene dosage effect. The process by which demyelination was
      initiated was associated with changes in myelin basic protein. An increased
      abundance of less cationic MBP (C-8) isomers occurred prior to demyelination.
      This increase was also associated with increased activity of peptidylarginine
      deiminase, the enzyme which converts arginine to citrulline in proteins, thereby
      providing a mechanism for generating less cationic forms of MBP. These data
      support a dosage effect of the DM20 transgene.

PMID- 8739150
TI  - Src, ras, and rac mediate the migratory response elicited by NGF and PMA in PC12
      cells.
AB  - The combination of nerve growth factor (NGF) and phorbol 12-myristate 13-acetate
      (PMA) rapidly induced the locomotion of PC12 cells by sequentially stimulating
      lamellar spreading, ruffling with pinocytosis, and polarization by retraction
      from the substratum. During migration, cells acquired long processes as a result
      of several undisrupted cell-substratum attachment points. The effect of NGF on
      PC12 migration was blocked by K-252a, a selective inhibitor of the trk family of
      receptor tyrosine kinases. When PMA was added to cells expressing pp60v-src, the
      cells displayed the same morphological behavior as they did with NGF and PMA
      addition. Activated ras only partially substituted for the effects of NGF; but,
      when ras was inhibited, the number of migrating cells decreased significantly due
      to a defect in spreading and retraction. Expression of an activated form of rac
      stimulated spontaneous growth of lamellipodia and enhanced cell migration in
      response to PMA. Expression of a dominant negative form of rac inhibited cell
      spreading and motility. Also, as a later effect, rac-inhibited cells extended
      much shorter neurites than wild type cells in response to NGF alone. These
      results indicate that the cytoarchitectural changes induced by NGF and PMA in
      PC12 cells are mediated by src, ras, and rac. Whereas ras and rac activation
      affect lamellipodia extension and retraction but not pinocytotic ruffling, src
      activation is involved in all three events.

PMID- 8739151
TI  - Neurofilament phosphorylation is modulated by myelination.
AB  - Axons undergo substantial changes in radial growth during the course of
      development. Recent evidence suggests that axonal diameter may be controlled by
      the state of neurofilament (NF) phosphorylation. Using dorsal root ganglion (DRG)
      Schwann cell co-cultures, we provide direct evidence that phosphorylation of NF
      is regulated by myelination. NF phosphorylation increased upon myelination of DRG
      neurons by Schwann cells. The increase in NF phosphorylation was reflected both
      as an increase in immunoreactivity with the antibody SMI31, specific for
      phosphorylation-dependent NF epitopes, and a concomitant decrease in
      immunoreactivity with SMI32, specific for nonphosphorylated NF epitopes. The
      increase in NF phosphorylation induced by myelination in the neuron-glia co
      cultures was similar to NF phosphorylation seen in sciatic nerve extracts of mice
      with normal myelination compared to Trembler J mouse littermates in which
      myelination of peripheral nerves is compromised. Using an in situ gel kinase
      assay, we have detected changes in individual NF kinase activities during
      myelination. In particular, a 35-kDa kinase activity was induced by myelination,
      whereas a 42-kDa kinase decreased in activity. We discuss the possibility that
      these and other kinases may be involved in signaling processes between neurons
      and glia during myelination.

PMID- 8739152
TI  - Opioid regulation of intracellular free calcium in cultured mouse dorsal root
      ganglion neurons.
AB  - Opioid agonists induced an increase in the intracellular free calcium
      concentration ([Ca2+]i) or an inhibition of K+ (25 mM)-stimulated increase in
      [Ca2+]i in different subsets of mouse dorsal root ganglion (DRG) neurons. The
      total neuronal population was grouped into three classes according to somatic
      diameter and defined as small ( < 16 microns), intermediate (16-25 microns), or
      large ( > 25 microns) neurons. Substance P-like immunoreactivity was detected
      mainly in the small and intermediate neurons. The delta, kappa, and mu opioid
      receptor agonists [D-Ser2,Leu5]enkephalin-Thr (DSLET), U69593, and [D-Ala2,
      MePhe4, Glyol5]enkephalin (DAMGO) each induced a transient increase in [Ca2+]i in
      a small fraction ( < 30%) of neurons. The increases in [Ca2+]i were blocked by
      the opioid antagonist naloxone. The dihydropyridine-sensitive calcium channel
      blocker nifedipine also blocked the increase in [Ca2+]i induced by 1 microM
      DSLET. The rank order of potency (percentage of cells responding to each opioid
      agonist) was DSLET > U69593 > DAMGO. The opioid-induced increase in [Ca2+]i was
      observed mainly in large neurons, with a low incidence in small and intermediate
      neurons. Opioid agonists also caused inhibition of K(+)-stimulated increases in
      [Ca2+]i, which were blocked by naloxone (1 microM). Inhibition of the K(+)
      stimulated increase by 1 microM DSLET or U69593 was greater in small and
      intermediate neurons than in large neurons.

PMID- 8739153
TI  - Myelin basic protein in experimental allergic encephalomyelitis is not affected
      at the posttranslational level: implications for demyelinating disease.
AB  - The microheterogeneity of myelin basic protein, expressed as the ratio between
      the least cationic (C-8) charge isomer and the most cationic (C-1), was examined
      in experimental allergic encephalomyelitis (EAE) cases. These included acute EAE
      of 2 months' duration induced with bovine proteolipid protein in complete
      Freund's adjuvant (CFA), chronic EAE induced with mouse spinal cord homogenate in
      varying doses from 0.5 to 2.0 mg in CFA, and chronic relapsing EAE of 12 months'
      duration induced with synthetic peptide 139-151 of the proteolipid protein
      sequence. The C-8/C-1 ratio was within the normal range for all groups of
      animals. However, the C-8/C-1 ratio was six- to sevenfold increased in a
      spontaneously demyelinating transgenic model, ND4, which contains 70 copies of
      the cDNA for DM20 (Mastronardi et al.: 1996). Since an increase in the C-8/C-1
      ratio was also observed in victims of multiple sclerosis but not other
      neurological diseases, the ND4 model may address primary changes prior to
      demyelination, while the EAE model addresses the autoimmune aspects of the
      disease.

PMID- 8739154
TI  - Expression and characterization of the rat alpha 4 beta 2 neuronal nicotinic
      cholinergic receptor in baculovirus-infected insect cells.
AB  - Baculovirus expression systems have been developed to generate 1) a neuronal
      nicotinic cholinergic receptor comprising both the alpha 4 and beta 2 subunits
      and 2) the alpha 4 and beta 2 subunits individually. The presence of the alpha 4
      and beta 2 genes in the various baculovirus-infected Sf9 cells was confirmed
      following polymerase chain reaction (PCR) of the extracted viral DNAs, gel
      electrophoresis, and double strand sequencing. Autofluorography, following sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis of infected cell lysates
      radiolabeled with 35S-methionine and immunoprecipated with mAb 270 (specific for
      the beta 2 subunit), revealed the presence of characteristic 52-kD bands in beta
      2- and alpha 4 beta 2 recombinant viral-infected cells, but not in control cells
      or cells infected with wild-type virus or recombinant virus containing alpha 4
      alone. The 52-kD protein, which is specific for mAb 270, is known to be the beta
      2 subunit of neuronal nAChRs. Specific [3H]methylcarbamylcholine binding was
      observed in cells infected with both alpha 4 or beta 2 but not with the alpha 4
      or beta 2 genes alone. Scatchard analysis revealed a Bmax = 5.50 pmol/mg and a Kd
      = 1 nM. The degree of [3H]methylcarbamylcholine binding/mg membrane protein was
      180-fold greater than that found in rat brain. The study demonstrates that the
      major neuronal nAChR, which comprises alpha 4 and beta 2 subunits and is present
      in very low abundance in mammalian brain, can be prepared by a baculovirus
      expression system in sufficient quantities for chemical and crystallographic
      structural analysis.

PMID- 8739155
TI  - Kainic acid activates transient expression of tenascin-C in the adult rat
      hippocampus.
AB  - Kainic acid-induced limbic seizures enhance expression of tenascin-C (TN) in the
      hippocampus of adult rats. TN mRNA was detectable by in situ hybridization in
      many granule cells in the dentate gyrus 4.5 hr after kainic acid injection but
      not in saline-injected animals (controls) or in animals killed 2 or 24 hr after
      injection. Thirty days after kainic acid injection, TN mRNA was detectable only
      in pyramidal cells of CA3 and CA1. At the protein level, TN was detectable by
      immunocytochemistry in control animals in the strata oriens and lacunosum
      moleculare of CA1, in the molecular layer, and within a narrow area at the inner
      surface of the granule cell layer in the dentate gyrus. Twenty-four hours after
      kainic acid injection, TN immunoreactivity was enhanced in these areas and
      throughout the granule cell layer. Thirty days after kainic acid injection, TN
      immunoreactivity was downregulated in these areas, while it was prominent in the
      stratum oriens and in clusters of immunoreactivity in the stratum lucidum of CA3.
      Western blot analysis of the hippocampus showed a peak of TN expression 24 hr
      after kainic acid injection. These observations show that TN expression is
      upregulated in predominantly neuronal cells already by 4.5 hr after kainic acid
      injection, coincident with activation of granule cells and sprouting of axon
      terminals, whereas the remaining TN expression 30 days after injection relates to
      pyramidal cells in CA1 and CA3, coincident with an astroglial response, as marked
      by a strong expression of glial fibrillary acidic protein.

PMID- 8739156
TI  - Glutamate release evoked by glutamate receptor agonists in cultured chick retina
      cells: modulation by arachidonic acid.
AB  - We studied the effect of ionotropic glutamate receptor agonists on the release of
      endogenous glutamate or of [3H]D-aspartate from reaggregate cultures
      (retinospheroids) or from monolayer cultures of chick retinal cells,
      respectively. Kainate increased the fluorescence ratio of the Na+ indicator SBFI
      and stimulated a dose-dependent release of glutamate in low (0.1 mM) Ca2+ medium,
      as measured using a fluorometric assay. Under the same experimental conditions,
      the release evoked by N-methyl-D-aspartate (NMDA; 400 microM) was about half of
      that evoked by the same kainate concentration; alpha-amino-3-hydroxy-5-methyl-4
      isoxasolepropionic acid (AMPA; 400 microM) did not trigger a significant
      response. In the presence of 1 mM CaCl2, all of the agonists increased the
      [Ca2+]i, as determined with the fluorescence dye Indo-1, but the glutamate
      release evoked by NMDA and kainate was significantly lower than that measured in
      0.1 mM CaCl2 medium. Inhibition by Ca2+ of the kainate-stimulated release of
      glutamate was partially reversed by the phospholipase A2 inhibitor oleiloxyethyl
      phosphorylcholine (OPC), suggesting that the effect was mediated by the release
      of arachidonic acid, which inhibits the glutamate carrier. Accordingly, kainate,
      NMDA, and AMPA stimulated a Ca(2+)-dependent release of [3H]arachidonic acid, and
      the direct addition of the exogenous fatty acid to the medium decreased the
      release of glutamate evoked by kainate in low (0.1 mM) CaCl2 medium. In monolayer
      cultures, we showed that NMDA, kainate, and AMPA also stimulated the release of
      [3H]D-aspartate, but in this case release in the presence of 1 mM CaCl2 was
      significantly higher than that evoked in media with no added Ca2+. The ranking
      order of efficacy for stimulation of Ca(2+)-dependent release of [3H]D-aspartate
      was NMDA > > kainate > AMPA.

PMID- 8739157
TI  - Regulation of brain m calpain Ca2+ sensitivity by mixtures of membrane lipids:
      activation at intracellular Ca2+ level.
AB  - Combinations of certain phospholipids and gangliosides increase the specific
      activity of m calpain and can activate m calpain at 1 to 10 microM Ca2+
      concentration. However, this level of calcium is still greater than the normal
      intracellular calcium level. We have used combinations of lipids to demonstrate
      the m calpain activity at the physiological Ca2+ level. GD1a (100 microM) and
      cerebroside (Cerb; 750 microM; 1:7.5) mixture was the most effective. At 0.5
      microM to 1.0 microM Ca2+ concentrations, 15-20% of the maximal activity was
      detected for the purified myelin and cytosolic m calpains. Other combinations
      were GD1a (100 microM), GM1 (100 microM), Cerb (750 microM), sulfatide (Sulf; 750
      microM), and phosphatidylinositol (PI; 300 microM) at a ratio of 1:1: 7.5:7.5:3,
      respectively. These lipid mixtures stimulated calpain activity at three- to
      tenfold less calcium concentration than control. The other mixtures, including
      GD1a:Sulf (1:9) > GD1a:PI (1:4) > PI:Sulf (1:5) > Cerb:Sulf (1:5) and PI:Cerb
      (1:2.5), also stimulated calpain activity at 1.0 microM Ca2+ concentration.
      Triton X-100, oxidized glutathione (GSSG), and calpain activator did not affect
      the Ca2+ requirement. Liposomes containing GD1a, Cerb, and m calpain also showed
      recognizable calpain activity at a significantly reduced Ca2+ concentration (0.4
      microM), confirming the glycolipid-mediated enzyme modulation. These studies
      indicate that specific lipid mixtures can stimulate m calpain activity at an
      intracellular level of Ca2+.

PMID- 8739158
TI  - Heat shock proteins and experimental autoimmune encephalomyelitis (EAE): I.
      Immunization with a peptide of the myelin protein 2',3' cyclic nucleotide 3'
      phosphodiesterase that is cross-reactive with a heat shock protein alters the
      course of EAE.
AB  - We describe sequence similarity and immunologic cross-reactivity between a
      peptide of the mycobacterial hsp, HSP65, and the myelin protein 2',3' cyclic
      nucleotide 3' phosphodiesterase (CNP). We demonstrate that immunization with the
      homologous cross-reactive CNP peptide (hsp-CNP peptide) has significant
      biological consequences. Rats immunized with hsp-CNP peptide in either complete
      Freund's adjuvant (CFA) or incomplete Freund's adjuvant (IFA) produce large
      amounts of peptide-specific antibody. Isotypes of antibodies in animals immunized
      with peptide in CFA are IgG1 and IgG2a. Isotypes of antibodies in rats immunized
      with peptide in IFA are predominantly IgG1, with low titers of IgG2a. T cell
      proliferative responses to HSP65 are present in rats immunized with peptide in
      CFA. T cell responses to HSP65 initially are absent in rats immunized with
      peptide in IFA but develop over time. T cell proliferative responses to hsp-CNP
      peptide were not detected. None of the groups of rats developed clinical or
      histologic evidence of experimental autoimmune encephalomyelitis (EAE). To induce
      EAE, rats preimmunized with hsp-CNP peptide were challenged with guinea pig
      spinal cord (GPSC) emulsified in CFA. Rats preimmunized with peptide in CFA
      developed severe EAE. Rats preimmunized with hsp-CNP peptide in IFA were
      protected from EAE, with both a lower incidence and severity of disease.
      Injecting the murine monoclonal antibody recognizing the shared HSP65 and CNP
      epitope did not protect against EAE. Our data suggest that a Th2 pattern of
      immune response to a CNP peptide that itself is non-encephalitogenic protects
      against EAE. Immune responses to either hsp or myelin proteins cross-reactive
      with hsp may play an important role in the development of EAE.

PMID- 8739159
TI  - Differential cellular response after glutamate analog hippocampal damage.
AB  - The tissue response after brain damage implicates the cellular "activation" of
      astrocytes and microglia. This glial response is referred as reactive gliosis.
      Using immunohistochemical markers, we have analyzed the neuronal and glial
      response to some neurotoxic-induced lesions. We have compared the effects of two
      glutamate analogs, AMPA and kainic acid, with those of traumatic injury. Our data
      showed that the time-course of appearance, the relative contribution of and the
      behavior of reactive astrocytes and microglial cells were clearly different after
      AMPA or kainic acid administration. The immunoreactivity associated with
      microglia response, with respect to the immunoreactivity associated with reactive
      astrocytes, was higher after AMPA damage than after kainic acid treatment. In
      both cases, however, glial cells were more abundant than after traumatic lesions.
      Interestingly, the CA1 pyramidal neurons affected by AMPA and some cortical
      neurons affected by traumatic injury responded with an overexpression of amyloid
      precursor protein, whereas no neuronal response was detected after the kainic
      acid treatment. Our data suggest that the gliotic response is highly specific to
      the type of insult and heterogeneous depending on the brain area affected.

PMID- 8739160
TI  - Periodontal reasons for tooth loss in an Asian population.
AB  - This study analysed data on periodontal reasons for tooth extractions, obtained
      from 52 dentists practising general dentistry in Singapore. The results revealed
      that, out of 2172 teeth extracted from 1276 patients, 35.8% were lost due to
      periodontal disease and 35.4% due to caries. Extraction due to periodontal
      problems increased with age, were more conspicuous in the Indian ethnic group and
      were frequently associated with pocketing and tooth mobility.

PMID- 8739161
TI  - Histological and microbiological aspects of ligature-induced periodontitis in
      beagle dogs.
AB  - This study was designed to investigate, using 6 beagle dogs, the levels of
      selected putative pathogens in healthy sites, in gingivitis sites, and in sites
      with histologically confirmed attachment loss. Levels of attachment loss
      increased with increasing periods of ligation and reached a maximum of 0.15 mm at
      57 days. Both histological attachment level and histological pocket depth were
      found to vary significantly with health/disease status (p < 0.0001). Higher
      numbers of total colony-forming units were seen for ligated sites than for
      healthy and gingivitis sites. Levels of Porphyromonas gingivalis and Prevotella
      intermedia also changed significantly with health/disease status (p < 0.001).
      These organisms showed their greatest increases at the time of the most intense
      attachment loss. Higher levels of Fusobacterium nucleatum were seen in the
      gingivitis sites than in healthy or ligated sites. Low levels of Campylobacter
      rectus and Capnocytophaga spp. were detected throughout. The morphometric
      microbiological analysis revealed unexpectedly high %s of motile rods, while
      spirochetes were found in very low %s. The total number of bacterial cells
      detected using phase contrast microscopy was not found to vary significantly.
      None of the morphotypes were demonstrated as showing significant changes with
      health/disease status.

PMID- 8739162
TI  - 0.1%/0.2% commercial chlorhexidine solutions as subgingival irrigants in chronic
      periodontitis.
AB  - This study compared 2 proprietary chlorhexidine (CH) products, Corsodyl (CO-0.2%
      CH, then ICI, U.K.) and Eludril (EL-0.1% CH, Pierre Fabre, France) as subgingival
      irrigants adjunctive to Simplified Oral Hygiene. 19 subjects, 8M, 11F, aged 30-57
      years, mean 44 years, took part. Probing pocket depth (PPD) ranged from 5-10 mm,
      mean 6.5 mm (CO and EL), with 60 CO and 65 EL sites. After oral hygiene
      instruction, without stress on interdental cleaning, patients received on visit
      supra- and subgingival debridement, and instruction in subgingival irrigation
      using the Max-I-Probe system (Smith & Nephew MPL, USA). For baseline, days 28
      (end of irrigation), 56 and 84, data were respectively: GI (medians): 1.7, 1.2,
      1.2, 1.0 (CO), 1.9, 1.5, 1.3, 1.0 EL); BOP (medians): 1.2, 0.4, 0.7, 0.4 (CO),
      1.5, 0.6, 0.6, 0.25 (EL); PPD (mm) (means): 6.3, 4.8, 4.2, 4.5 (CO), 6.8, 5.2,
      5.3, 4.7 (EL); PAL (mm) (means-change relative to day 0): 0.6, 0.5, 0.8 (CO),
      0.8, 0.8, 1.5 (EL). By Wilcoxon for non-parametric and t-tests for parametric
      data, both groups showed significant improvement for all variables at all times
      relative to baseline, with only one significant difference between the groups, in
      favour of EL, for PAL at day 84 (p < 0.05). This pilot study indicates that both
      simplified oral hygiene regimes are effective in periodontitis, but that there
      was no difference between the 2 commercial irrigants as adjunctives.

PMID- 8739163
TI  - Root cleaning or root smoothing. An in vivo study.
AB  - The goal of the present study was to determine whether the clinical treatment
      results in terms of pocket probing depth reduction and attachment gain would be
      different following conventional periodontal flap surgery if, on the one hand,
      root surfaces were smoothed after plaque and calculus removal or, on the other
      hand, root surfaces were first thoroughly cleaned but then intentionally
      roughened. 13 adult patients with moderate periodontitis participated; the same
      patients acted as a unit of control. Evaluations were performed on a total of 224
      sites on 81 anterior and premolar teeth. On the 41 test teeth (111 sites), a
      coarse diamond stone was used following traditional root planing to roughen the
      root surfaces. The 40 control teeth (113 sites) were cleaned and planed using
      Gracey curettes. Measurements performed 3 and 6 months post-surgery revealed
      significant reductions in probing depths at both "rough" and "smooth" sites.
      However, no differences between the 2 methods were detected. This was true also
      with regard to attachment gain. We conclude that striving for root surface
      smoothness during periodontal surgery appears unnecessary.

PMID- 8739164
TI  - Human gingival crevicular fluid keratin at healthy, chronic gingivitis and
      chronic adult periodontitis sites.
AB  - The present study was designed to determine, in a cross-sectional study, whether
      there was any relationship between the keratin-positive material in gingival
      crevicular fluid and the clinical periodontal status. Keratins were selected as
      putative indicators of degradation of epithelial cells cytoskeletal proteins.
      Keratin positive material was determined by enzyme-linked immunosorbent assay in
      42 subjects exhibiting clinical sites of health, chronic gingivitis and chronic
      periodontitis. The concentration of keratin in parotid saliva was also measured
      for each subject. Keratin concentration in gingival crevicular fluid samples was
      significantly greater at sites exhibiting signs of gingivitis and periodontitis
      compared with healthy sites. No differences were detected between sites
      exhibiting gingivitis and periodontitis. No differences were found between the 3
      groups for the saliva keratin-positive material which was significantly less than
      that detected in gingival crevicular fluid. These results suggest that gingival
      crevicular fluid keratin concentration may serve as a marker of gingival damage.

PMID- 8739165
TI  - Response to periodontal therapy in patients with high or low levels of P.
      gingivalis, P. intermedia, P. nigrescens and B. forsythus.
AB  - In a previous study, subjects receiving either adjunctive tetracycline or
      Augmentin showed, on average, more attachment level gain 10 months post-therapy
      than subjects receiving either Ibuprofen or a placebo, although some subjects in
      each treatment group showed loss of attachment post-therapy. Since differences in
      treatment response might have been due to differences in the subgingival
      microbiota, the response to different therapies in subjects with different pre
      therapy subgingival microbiotas was evaluated. 29 subjects exhibiting loss of
      attachment > 2.5 mm at 1 or more sites during longitudinal monitoring were
      treated by modified Widman flap surgery at deep sites, subgingival scaling at all
      other sites and were randomly assigned one of the following agents: Augmentin,
      tetracycline, ibuprofen or a placebo. Treatment was completed within 30 days,
      during which time the subject took the assigned agent. Subgingival plaque samples
      were taken from the mesial surface of each tooth at each visit and evaluated for
      their content of 14 subgingival species including P. gingivalis, P. nigrescens,
      P. intermedia and B. forsythus using DNA probes. 18 subjects with mean counts >
      10(5) of 2 or more of these 4 species comprised the high test species group; 11
      subjects with mean counts > 10(5) of 0 or 1 of the species, the low test species
      group. Because this was a post-hoc analysis, the number of subjects in some of
      the treatment/test species groups was small. However, the 8 high test species
      subjects who received tetracycline showed the most attachment level gain (0.83 +/
      0.20 mm), while the 3 tetracycline-treated, low test species subjects showed
      minimal gain (0.05 +/- 0.28 mm) 10 months post-therapy. Low test species subjects
      receiving Augmentin (n = 2) showed a mean gain in attachment of 0.67 (+/- 0.59)
      mm. The mean % of sites showing either attachment gain or loss > or = 2 mm was
      computed for each treatment/test species group. High test species subjects
      receiving tetracycline exhibited the best ratio of gaining to losing sites
      (16.2), followed by low test species subjects receiving Augmentin (14.1).
      Periodontal pockets < 7 mm pre-therapy in low test species subjects treated with
      Augmentin and high test species subjects treated with tetracycline showed
      attachment gain more frequently than attachment loss. The greatest proportion of
      gaining sites was seen at pockets > 6 mm, particularly in subjects receiving
      adjunctive tetracycline. Overall, the data indicated that a gain in mean
      attachment level post-therapy was significantly associated (p < 0.001) with an
      increase in C. ochracea accompanied by a decrease in B. forsythus, P. gingivalis,
      P. intermedia and P. nigrescens. The 4 test species were decreased more in
      subjects receiving tetracycline. In contrast, Augmentin appeared to be effective
      in decreasing the % sites colonized by A. actinomycetemcomitans and in increasing
      the proportion of sites colonized by C. ochracea. Knowledge of the baseline
      microbiota should improve the choice of an appropriate adjunctive antibiotic for
      periodontal therapy.

PMID- 8739166
TI  - Utility of 5 major putative periodontal pathogens and selected clinical
      parameters to predict periodontal breakdown in patients on maintenance care.
AB  - The predictive utility of 5 major putative periodontopathic microbial species,
      "superinfecting" organisms, and several clinical periodontal parameters were
      assessed relative to periodontitis recurrence over a 12-month period in 78
      treated adult patients participating in a 3-month maintenance care program. At
      baseline, pooled subgingival microbial samples were collected from each patient,
      and whole-mouth evaluations of probing depth, relative periodontal attachment
      level, furcation involvement, and indices of plaque and gingival inflammation
      were carried out. 67 (85.9%) subjects were culture-positive at baseline for
      presence of either Actinobacillus actinomycetemcomitans, Porphyromonas
      gingivalis, Prevotella intermedia, Campylobacter rectus or Peptostreptococcus
      micros, with 48 (61.5%) subjects yielding one or more of these species at or
      above designated threshold proportions of > or = 0.01% for A.
      actinomycetemcomitans, > or = 0.1% for P. gingivalis, > or = 2.5% for P.
      intermedia, > or = 2.0% for C. rectus, and > or = 3.0% for P. micros. Subgingival
      yeasts were recovered from 12 subjects, staphylococci from 7, and enteric
      rods/pseudomonads from 6; however, no subjects revealed > or = 1.0% baseline
      proportions of these "superinfecting" organisms in subgingival specimens.
      Periodontitis recurrence in subjects was defined as any periodontal site
      exhibiting either a probing depth increase of > or = 3 mm from baseline, or a
      probing depth increase of > or = 2 mm from baseline together with a loss in
      relative periodontal attachment of > or = 2 mm from baseline. 15 (19.2%) study
      subjects showed periodontitis recurrence within 6 months of baseline, and 25
      (32.1%) within 12 months. The mere baseline presence of the 5 major test species
      and "superinfecting" organisms were not significant predictors of periodontitis
      recurrence over 12 months. However, a 2.5 relative risk for periodontitis
      recurrence over 12 months was found for subjects yielding one or more of the 5
      major test species at or above the designated baseline threshold proportions (p =
      0.022, Mantel-Haenszel chi 2 test). The positive predictive value for
      periodontitis recurrence of a microbiologic analysis encompassing the 5 major
      test species at or above the designated threshold proportions improved with
      increasing time from baseline, up to approximately 42% at 12 months. Baseline
      variables jointly providing in multiple regression analysis the best predictive
      capability for periodontitis recurrence in subjects over a 12-month period were
      recovery of one or more of the 5 major test species at or above designated
      threshold proportions, the proportion of sites per subject with > or = 5 mm
      probing depth, and the mean whole-mouth probing depth. These findings indicate
      that one or more of 5 major putative periodontal pathogens in elevated
      subgingival proportions together with increased probing depth predispose adults
      on maintenance care to recurrent periodontitis.

PMID- 8739167
TI  - Efficacy of CPITN sextant scores for detection of periodontitis disease activity.
AB  - The relationship between CPITN sextant scores and periodontitis recurrence at
      individual tooth sites was evaluated in a longitudinal study in 83 treated adult
      periodontitis patients receiving systematic 3-month maintenance care. At baseline
      and semi-annual examinations over 36 months, CPITN scores were assigned to each
      dentition sextant using probing depths and gingival index scores, and relative
      periodontal attachment level was assessed at individual tooth sites using an
      occlusal reference stent. Periodontitis recurrence was defined as any periodontal
      site exhibiting either a probing depth increase of > or = 3 mm from baseline, or
      a probing depth increase of > or = 1 mm from baseline together with a loss of
      relative periodontal attachment of > or = 2 mm from baseline. 49 (59.0%) subjects
      developed periodontitis recurrence in 147 (29.8%) sextants at 181 (2.2%)
      individual periodontal sites during the 36-month study period. Baseline CPITN
      scores of 4 were more common in disease-active subjects than clinically-stable
      subjects (p = 0.003, t-test), and were associated with a statistically
      significant 1.66 relative risk of periodontitis recurrence within 36 months.
      CPITN sextant scores of 3 or 4 showed low specificity and low positive predictive
      values as indicators of periodontitis recurrence at > or = 1 individual sites
      within the affected sextant. In comparison, low CPITN sextant scores (0-2)
      provided high specificity (96.2-100%), high positive predictive values (99.5
      100%), and a summary odds ratio of 24.2 as an indicator of clinical stability at
      all periodontal sites within a given dentition sextant. Changes in sextant scores
      for CPITN over 6-month periods showed no relationship with periodontitis
      recurrence at individual periodontal sites. This study suggests that while CPITN
      is inadequate for detection of periodontitis recurrence, low CPITN scores provide
      rapid presumptive identification of clinically-stable sextants in adult
      periodontitis patients on maintenance care.

PMID- 8739168
TI  - The relationship between clinical attachment loss and the duration of insulin
      dependent diabetes mellitus (IDDM) in children and adolescents.
AB  - The periodontal status of 77 diabetic children and adolescents, and 77 paired,
      systemically-healthy, sex- and age-matched control subjects, was clinical
      examined. Fasting blood glucose, fructosamine and glycosylated haemoglobin (HbA1)
      values were determined. The mean periodontal pocket depths, clinical attachment
      levels and the parameters to assess diabetes mellitus from the diabetic group
      were significantly higher than those of the controls. We found a positive
      correlation between the duration of diabetes and clinical attachment loss, but
      not with periodontal probing depth, plaque index and gingival index in the
      diabetic group. A positive correlation was also assessed between the present
      serum fructosamine and gingival index in the diabetic group, but not in controls.

PMID- 8739169
TI  - The distribution of gingival overgrowth in organ transplant patients.
AB  - The distribution of gingival overgrowth was investigated in a cohort of organ
      transplant patients, who were medicated with cyclosporin or the combination of
      cyclosporin and a calcium channel blocking drug. Gingival overgrowth scores were
      significantly higher at buccal sites than lingual-palatally (p < 0.0001). There
      was no significant difference between upper and lower overgrowth scores (p =
      0.88). The most severe overgrowth was seen in the canine region. Overgrowth
      between the central incisors was significantly less than in the canine region (p
      > or = 0.044) and was similar to that in the molar and premolar region. Although
      raised overgrowth scores were associated with increased levels of plaque and
      gingival inflammation, the distribution could not be explained by this
      observation.

PMID- 8739170
TI  - Comparative study of plaque and gingivitis prevention by AmF/SnF2 and NaF. A
      clinical and microbiological 9-month study.
AB  - This comparative clinical 9-month study was designed to examine the efficacy of
      amine/stannous fluoride (AmF/SnF2) (Meridol) and sodium fluoride (NaF). 150
      probands with chronic gingivitis or early signs of periodontitis were divided
      into 3 randomised groups. Group 1 was given a NaF toothpaste and an NaF
      mouthrinse, group 2 AmF/SnF2 toothpaste and mouthrinse, and group 3 AmF/SnF2
      toothpaste and NaF mouthrinse. The probands were examined at intervals (0, 1, 3
      and 9 months) under conditions of a clinical double-blind study. The parameters
      recorded were the plaque index (PlI), the approximal plaque index (API), the
      gingival index (GI) and the mod. sulcus bleeding index (SBI). The probing depths
      (PD) were also measured. The composition of the supragingival plaque was
      evaluated by dark-field microscopy. A highly significant reduction in all
      clinical parameters was recorded in all 3 groups in the course of the study. The
      most pronounced reduction in PlI, API, SBI and PD was recorded in group 2. In the
      group comparison, however, no significant differences were recorded.
      Microbiological examination revealed a highly significant increase in cocci and a
      decrease in rods in all 3 groups. There was also a significant reduction in
      spirochetes, filaments and fusiforms in groups 2 and 3. In group 1, there was a
      significant fall only in fusiforms and small spirochetes. Overall, no significant
      difference in clinical parameters was recorded in the group comparison. However,
      the use of AmF/SnF2 toothpaste and mouthrinse (group 2) and, to a lesser degree,
      the combined use of AmF/SnF2 toothpaste and NaF mouthrinse display a favorable
      microbiological effect. The results from the present double-blind study reveal a
      reduction in gingival inflammation and supragingival plaque accumulation with a
      positive change in plaque flora in all groups. The reduction in potentially
      gingivopathogenic bacteria was slightly higher in the amine/stannous fluoride
      group.

PMID- 8739171
TI  - The effect of age on the development of gingivitis. Clinical, microbiological and
      histological findings.
AB  - In the present "experimental gingivitis" study, the response of the marginal
      gingiva to plaque formation was studied in one group of young subjects, 20-25
      years of age, and in one group of older subjects, aged 65-80 years. During a 4
      week period, all subjects received a series of professional tooth cleaning to
      establish healthy gingival conditions. A baseline examination (Day 0) included
      assessments of plaque and gingivitis. Sites that were examined (the experimental
      sites) included the mesio-palatal, palatal, and disto-palatal surfaces of all
      teeth present in the 15 ... 25 tooth region. Among the experimental sites,
      microbial sampling and gingival fluid assessment were performed and one gingival
      biopsy harvested from each subject. Following the baseline examination, the
      participants abolished mechanical tooth cleaning measures in the palatal and
      approximal surfaces of 15 ... 25. The clinical examination and the gingival fluid
      measurement were repeated on days 7, 14 and 21 of no oral hygiene. The
      microbiological sampling and the biopsy procedure were repeated on days 7 and 21.
      The data collected demonstrated that old subjects, during a 3-week period of oral
      hygiene abstention, formed similar amounts of plaque as the young subjects, but
      developed more gingivitis than young subjects. Thus, the clinical gingivitis
      assessments, the gingival fluid measurements and morphometric determinations made
      in the biopsy samples documented that the gingival lesion which formed in the old
      individuals was more pronounced and contained more inflammatory cells than the
      corresponding lesion in the young subject sample.

PMID- 8739172
TI  - Systemic antimicrobial treatment and guided tissue regeneration. Clinical and
      microbiological effects in furcation defects.
AB  - The purpose of this investigation was to study the microbiota associated with
      furcation-involved teeth before and after treatment by the guided tissue
      regeneration procedure (GTR) with non-resorbable ePTFE membranes, and to evaluate
      the benefit of additional systemic antimicrobial therapy (ornidazole). Each of 10
      patients contributed 1 pair of bilateral mandibular molars with comparable
      furcation defects. 5 defects were treated with a membrane and the active drug, 5
      were treated without a membrane but with the active drug, 5 were treated with a
      membrane and a placebo, and 5 were treated with neither a membrane nor the active
      drug. Considerable differences were found in the healing response of furcation
      defects treated with or without the antimicrobial agent. More horizontal
      attachment gain and increase in bone density was obtained in patients receiving
      the active drug than in patients receiving the placebo. With 1 exception, all
      sites with increasing horizontal probing depth were found in patients of the
      placebo group. Treatment with membrane plus ornidazole resulted in 0.7 mm mean
      recession and -1.2 mm mean decrease in horizontal probing depth. Sites treated
      with membranes generally tended to be positive for 15 target micro-organisms more
      often than sites treated without a membrane. This was particularly evident for
      Fusobacterium, Prevotella intermedia and Actinomyces odontolyticus. Whereas GTR
      treated sites were often already positive upon removal of the membrane, re
      emergence of target organisms seemed to be more delayed in the conventionally
      treated sites.

PMID- 8739173
TI  - Clinical evaluation of tine shape of 3 periodontal probes using 2 probing forces.
AB  - The objective of this study was to evaluate the effect of the tine shape of 3
      different periodontal probes. One tapered, one parallel-sided and one WHO-probe
      tine, each with a diameter of 0.5 mm at the tip, were mounted in hinged handles
      exerting a constant probing force (Brodontic). The handles were adjusted to
      either 0.25 N (127 N/cm2) or 0.5 N (255 N/cm2). 12 patients with moderate to
      severe periodontitis were measured after supra- and subgingival debridement,
      using all 6 possible tine/force combinations in 3 sessions. In each session one
      tine/force combination was used in the 1st and 3rd quadrants, and another
      tine/force combination in the 2nd and 4th quadrant. The measurements in the same
      quadrants could therefore be used for comparisons within the same site. The
      selection for the 2 quadrants in which a given tine/force combination was to be
      used, was randomised. Calculations of differences (mean per patient) between
      probing measurements show that the WHO tine yields deeper recording than the
      parallel/sided and tapered tines, both at 127 N/cm2 and 255 N/cm2. We conclude
      that in addition to probing force, the tine shape of a periodontal probe is of
      significant importance for the recorded probing depth.

PMID- 8739174
TI  - Bacterial morphotypes of 3-day old plaque in Chinese. A pilot study.
AB  - The aim of the this study was to estimate the % distribution of bacterial
      morphotypes of supragingival plaque in Chinese subjects after 3 days of no oral
      hygiene. 36 dental students, hygienists or dental surgery assistants (mean age:
      24.3 years) were recruited. Prophylaxis and oral hygiene reinforcement were given
      1 x a week for 3 weeks to obtain gingival health and a 3-day period without any
      plaque control started afterwards. At the end of the 3-day period, the plaque
      along the gingival margin of the upper right central incisor was removed and
      direct Gram stained smears were prepared for light microscopy. Bacteria were
      classified as gram-positive or gram-negative cocci, rods, filaments, fusiform
      organisms, spirilla or spirochetes. A differential count of 200 organisms from 3
      6 microscopic fields was performed and the results expressed as a % of the
      organisms counted. Results from the 36 direct smears showed approximately 83%
      (range: 52%-96%) of the organisms to be gram-negative while gram-positive
      bacteria comprised only a minority of about 12% (range: 0.7%-43%). This result is
      remarkably different from previous reports from the West where gram-positive
      bacteria were the predominant bacterial types noted in early supragingival
      plaque. Further longitudinal studies involving both microscopy and
      bacteriological culture will be necessary to confirm this finding.

PMID- 8739175
TI  - Comparison of an oscillating/rotating electric toothbrush and a 'sonic'
      toothbrush in plaque-removing ability. A professional toothbrushing and
      supervised brushing study.
AB  - The purpose of the present study was to compare the Braun/Oral-B Plak Control
      (D7) and Sonicare (S) in their plaque-removing efficacy. For this study, 35
      university students (non-dental) were selected. This was a 2-part study. Prior to
      each appointment, all subjects were asked to abstain from all oral hygiene
      procedures for at least 24 h. In Part 1, the efficacy of the toothbrush was
      studied when one of the investigators brushed the teeth of the panellists. In
      Part 2, the efficacy of toothbrushing was studied after the students had received
      professional instruction. The available time for the brushing amounted to a total
      of 2 min per mouth. Dental plaque was evaluated by means of the Silness and Loe
      plaque index assessed at 6 sites per tooth. Results showed that both in Part 2
      and Part 1 the D7 removed significantly more plaque than the S-electric
      toothbrush. The plaque reduction assessed according to Silness and Loe in Part 1
      was for the D7, 1.28 and for the S, 1.12. In Part 2, the reductions were 0.90 and
      0.80, respectively. The majority (n = 34) of subjects preferred the D7 over the
      S. In conclusion, the results of the present study show that the
      oscillating/rotating toothbrush (Braun/ Oral-B Plak Control) is more effective in
      plaque removal than the sonic electric toothbrush (Sonicare). In addition, given
      a choice, the panellists preferred the oscillating/rotating electric toothbrush.

PMID- 8739176
TI  - Effects of sho-saiko-to on production of prostaglandin E2 (PGE2), leukotriene B4
      (LTB4) and superoxide from peripheral monocytes and polymorphonuclear cells
      isolated from HIV infected individuals.
AB  - The effects of Sho-saiko-to (SST), a traditional Chinese medicine, on the
      production of PGE2 from monocytes, LTB4 and superoxide from polymorphonuclear
      cells (PMNC) in HIV infected individuals were studied. SST inhibited the
      production of PGE2 from monocytes stimulated by opsonized zymosan in all groups
      including the healthy control group and also inhibited the production of
      superoxide from PMNC after stimulation with FMLP. On the other hand, SST enhanced
      the production of LTB4 when PMNC were stimulated by the calcium ionophore A23187.
      These results suggest that SST has different effects on the production of
      prostanoids or superoxide from monocytes and PMNC. Furthermore, our data
      indicates that inhibition of PGE2 or superoxide production will lead to indirect
      suppression of HIV, and enhancement of LTB4 will contribute to the upregulation
      of the immune reaction in HIV infected individuals.

PMID- 8739177
TI  - Superoxide anion scavenging effect of coumarins.
AB  - The superoxide scavenging effects of fifteen coumarins were tested on the
      xanthine-xanthine oxidase-cytochrome C system. The results showed that
      fraxetin(10) displayed the strongest activity, and its percent inhibition at 100,
      10 and 1 muM were 100, 100 and 53.13% respectively. Esculetin(4) showed the
      second strongest activity resulting in percent inhibition at 100 and 10 muM were
      87.16 and 52.38% respectively. Both fraxetin(10) and esculetin(4) have been
      isolated from the plant, Fraxinus bungeana DC (Oleaceae) which has been used in
      folk medicine as an analgesic and anti-inflammatory medicine. It seems that two
      phenolic hydroxy groups in the ortho position in the molecule of coumarins play
      an important role in scavenging activity.

PMID- 8739178
TI  - Modulation of microsomal cytochrome P450 by Scutellariae Radix and Gentianae
      scabrae Radix in rat liver.
AB  - The present study has determined the effects of Scutellariae Radix (Huangqin) and
      Gentianae scabrae Radix (Longdan) on liver microsomal cytochrome P450 (P450)
      dependent mono-oxygenases using rats pretreated with crude extracts of medicinal
      herbs. Scutellariae Radix resulted in a 53% decrease of pentoxyresorufin O
      dealkylase activity in liver microsomes. In contrast, Gentianae scabrae Radix
      caused a 50% increase of benzo(a)pyrene hydroxylase activity. Immunoblotting
      analysis of liver microsomes revealed that Scutellariae Radix induced and
      suppressed the levels of P450 1A and 2B proteins, respectively. Scutellariae and
      Gentianae scabrae Radixes had no effects on microsomal aniline hydroxylase
      activity and P450 2E1 protein.

PMID- 8739179
TI  - The anti-inflammatory activity of Scutellaria rivularis extracts and its active
      components, baicalin, baicalein and wogonin.
AB  - Five extracts (n-hexane, chloroform, ethyl acetate, n-butanol and water) of
      Scutellaria rivularis Benth. were evaluated for their anti-inflammatory activity
      against carrageenan-induced paw edema in rats and compared with indomethacin. The
      result indicated that chloroform extract proved to be the most effective in all
      of the extracts. Consequently, three major components (baicalin, baicalein and
      wogonin) of the chloroform extract were further tested for their anti
      inflammatory activity using the same model. It was found that baicalin exhibits
      the greatest inhibition activity against carrageenan-induced rat paw edema.

PMID- 8739180
TI  - Effect of shi-ka-ron on cytokine production of lymphocytes in mice treated with
      cyclophosphamide.
AB  - The effect of Shi-ka-ron (CX) on cytokine production of lymphocytes in mice
      treated with cyclophosphamide was investigated. Shi-ka-ron, a traditional Chinese
      prescription, consists of 8 crude Chinese herbal extracts. Its main efficacy is
      to strengthen the body resistance. We observed that each CX component stimulated
      interleukine-2 and interferon-gamma production of murine splenic lymphocytes both
      in vitro and in vivo. IL-2 and IFN-gamma production of splenic lymphocytes were
      also examined in mice treated with CX combined with cyclophosphamide (CY) in
      vivo. We found that CX not only could increase IL-2 and IFN-gamma production in
      vitro, but also in vivo at suboptimal concentration.

PMID- 8739181
TI  - Si-jun-zi-tang regulate granulocyte macrophage colony-stimulating factor
      secretion by human peripheral blood mononuclear cells.
AB  - Si-Jun-Zi-Tang is one of the widely used Chinese herbal medicines. In this study,
      human peripheral blood monocytes were treated in vitro with 50% hot ethanol
      extract of Si-Jun-Zi-Tang and its four major ingredients (Dangshen, Baizhu,
      Gancao and Fuling). The concentration of granulocyte-macrophage colony
      stimulating factor (GM-CSF) in the culture supernatant at 3 hours and 18 hours
      were measured using an ELISA. Dangshen and Gancao significantly suppressed GM-CSF
      secretion in a dose-dependent manner. Baizhu showed no statistically significant
      effect on GM-CSF secretion 18 hours after in vitro drug-treatment. Fuling, by
      contrast, significantly augmented GM-CSF secretion in a dose-dependent manner
      after 18 hours of drug treatment. Si-Jun-Zi-Tang showed a suppressive effect on
      GM-CSF secretion at 3 hours but significantly augmented GM-CSF secretion when the
      cells were treated with 8 mg/ml of the drug for 18 hours. The data suggested that
      Si-Jun-Zi-Tang might modulate hematopoiesis and immune response via regulating GM
      CSF secretion, and the presence of Fuling in Si-Jun-Zi-Tang could counteract the
      suppressive effect of Dangshen and Gancao on GM-CSF secretion.

PMID- 8739182
TI  - Effects of chaihu-guizhi-ganjiang-tang on the levels of monoamines and their
      related substances, and acetylcholine in discrete brain regions of mice.
AB  - The effects of the extract powder (CggT) from Chaihu-Guizhi-Ganjiang-Tang (Saiko
      keishi-kankyo-to, in Japanese) on the monoamines and their related substances and
      the acetylcholine in mouse brain were examined. 1) A single administration of
      CggT significantly increased the levels of HVA and 5-HIAA in the cerebral cortex,
      hypothalamus, corpus striatum and hippocampus at 75 mg/kg, and those in the
      hypothalamus, corpus striatum and hippocampus at 750 mg/kg. 2) The repeated
      administration of CggT significantly increased the level of 5-HT in the
      hippocampus at 75 mg/kg, and the levels of 5-HT in the corpus striatum and of NE
      and 5-HT in the hippocampus at 750 mg/kg. 3) The level of ACh was significantly
      increased in the hypothalamus alone after single administration of CggT. These
      findings suggest that CggT stimulates function of the dopaminergic and
      serotonergic nervous systems in mice, but not most of the NEnergic and
      cholinergic nervous systems.

PMID- 8739183
TI  - Inhibitory effects of 1-hydroxyethylidene-1,1-bisphosphonate and Chinese
      traditional (kampo) medicines on calcification of the heart and tongue in
      DBA/2NCrj mice.
AB  - The effects of 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) and two Chinese
      traditional (Kampo) medicines, Dai-saiko-to and Saiko-ka-ryukotsu-borei-to on
      spontaneous soft tissue (heart and tongue) mineralization in DBA/2NCrj mice were
      studied. These agents were given orally for 4 weeks to DBA/2NCrj mice. After 2
      weeks of administration in the heart, 0.006 and 0.03% (w/v) HEBP decreased
      calcium content by 90 and 30%, respectively, while 0.27 and 2.7 mg/ml Dai-saiko
      to reduced calcium content by 30 and 45%, respectively. Saiko-ka-ryukotsu-borei
      to (0.27 mg/ml) reduced both calcium and phosphorus content by 50 and 35%,
      respectively. However, their inhibitory effects on the heart were not observed
      after 4 weeks of administration. The compounds delayed the onset of increases of
      bulk calcium and phosphorus content. In the tongue, at 4 weeks, 0.006 and 0.03%
      (w/v) HEBP reduced calcium content by 30 and 45%, respectively, while two Kampo
      medicines (at both concentrations used) significantly reduced the content of
      calcium (by 27-79%) and phosphorus (by 24-32%). These results strongly suggest
      that two Kampo medicines as well as HEBP may be useful in preventing and curing
      soft tissue calcification.

PMID- 8739184
TI  - Stimulative effects of gusuibu (Drynaria baronii) injection on chick embryo bone
      primordium calcification in vitro.
AB  - Through tissue culture and isotope tracing, it was found that Gusuibu (Drynaria
      baronii) injection (GI) significantly promoted calcification of the cultivated
      chick embryo bone primordium (CEBP), increased ALP activity in the cultivated
      tissue, and accelerated synthesis of proteoglycan. It was also confirmed that the
      promotion of proteoglycan synthesis was an important factor in the promotion of
      calcification.

PMID- 8739185
TI  - Protective effects of Gynostemma pentaphyllum in gamma-irradiated mice.
AB  - Radiation protective effects of Gynostemma Pentaphyllum (Gp) were investigated in
      gamma-irradiated mice. Animals were sacrificed on days 5, 15, 25 and 35 after
      gamma-irradiation. GOT, GPT, serum IgG and leukocyte counts were measured.
      Proliferation of splenocytes stimulated by mitogens, such as PHA, Con A, and LPS
      were detected and compared. The results showed that all parameters measured in
      this study were decreased and proliferation of splenocytes stimulated by mitogens
      were repressed in gamma-irradiated mice. Gp helped to recover the decreased
      leukocyte counts, GOT, GPT and IgG in serum and the proliferation of splenocytes
      stimulated by PHA, LPS and Con A in the gamma-ray irradiated mice.

PMID- 8739186
TI  - The prandial effect on the pulse spectrum.
AB  - The prandial effect on the pulse spectrum of the radial artery was studied.
      Ingestion greatly affected the spectrum of the pressure pulse. For most of the
      tested subjects, the harmonic proportions of the 2nd and the 4th harmonic
      increased significantly after ingestion, however a decreasing effect was found on
      the 5th, 6th, 7th, 8th, 9th harmonics. The spectrum became stable from half hour
      after ingestion and last 3 to 4 hours. From these results, a reliable pulse
      diagnosis is therefore suggested to be done in the period when the pulse spectrum
      is stable; physiological significance of these postprandial phenomena is also
      discussed.

PMID- 8739187
TI  - Radioactive pathways of hypodermically injected technetium-99m.

PMID- 8739188
TI  - The occurrence of glycine in bacterial lipopolysaccharides.
AB  - The aminoacyl analysis of endotoxic lipopolysaccharides (LPS) isolated from
      several bacteria revealed essential amounts of glycine, among the inherent LPS
      components. Significant amounts of the glycine was detected in
      lipopolysaccharides isolated from over 30 strains of Escherichia, Salmonella,
      Hafnia, Citrobacter and Shigella species. Glycine as a single amino acid was
      found only in a core part of LPS. Molar ratio of glycine in core oligosaccharide
      fraction ranged from 0.2 to 0.6 per 3 heptoses. The oligosaccharide enriched in
      glycine was isolated using the HPLC. The amino acid appeared to be terminally
      located in a core oligosaccharide. The labelling of the lipopolysaccharide cores
      was achieved when the bacteria were cultivated in the presence of radioactive
      [14C]glycine. The labelled core oligosaccharide released the radioactivity during
      treatment with mild alkali or acid (0.1 M NaOH or HCl, 100 degrees C, 4 h). The
      radioactivity in SDS-polyacrylamide gel electrophoresis migrated exclusively with
      LPS. The results indicate that amino acid is an integral constituent of core
      oligosaccharide in lipopolysaccharide.

PMID- 8739189
TI  - Potentiation of lethal endotoxin shock by streptococcal pyrogenic exotoxin in
      rabbits: possible relevance of hyperreactivity of macrophages to endotoxin.
AB  - Streptococcal pyrogenic exotoxin (SPE) potentiates lethal shock induced by
      endotoxin. We have previously reported that macrophages derived from SPE-treated
      rabbits showed hyperreactivity to endotoxin, and that the effect of SPE on
      macrophages was mediated by a lymphokine(s). Here we show that culture
      supernatants of SPE-stimulated lymphocytes, when administered into rabbits three
      hours before or together with endotoxin, potentiate a variety of endotoxin
      induced pathophysiological changes and even lethal shock. These results suggest
      that SPE-induced lymphokine(s) mediates the potentiating effect of SPE on the
      lethal endotoxin shock through enhancing endotoxin reactivity of macrophages
      which play the central role in mediating endotoxin toxicity.

PMID- 8739190
TI  - Inhibition of Helicobacter pylori by garlic extract (Allium sativum).
AB  - The antibacterial effect of aqueous garlic extract (AGE) was investigated against
      Helicobacter pylori. Sixteen clinical isolates and three reference strains of H.
      pylori were studied. Two different varieties of garlic were used. The
      concentration of AGE required to inhibit the bacterial growth was between 2-5 mg
      ml-1. The concentration, for both AGE types, to inhibit 90% (MIC90) of isolates
      was 5 mg ml-1. The minimum bactericidal concentration (MBC) was usually equal to,
      or two-fold higher than, minimum inhibitory concentration (MIC). Heat treatment
      of extracts reduced the inhibitory or bactericidal activity against H. pylori;
      the boiled garlic extract showed a loss of efficacy from two- to four-fold the
      values of MIC and the MBC obtained with fresh AGE. The antibacterial activity of
      garlic was also studied after combination with a proton pump-inhibitor
      (omeprazole) in a ratio of 250:1. A synergistic effect was found in 47% of
      strains studied; an antagonistic effect was not observed.

PMID- 8739191
TI  - Investigation of animal botulism outbreaks by PCR and standard methods.
AB  - A double PCR procedure is proposed for identification of Clostridium botulinum C
      and D. This method consists of a first PCR amplification with a degenerate primer
      pair able to amplify a 340 bp common DNA fragment from botulinum neurotoxin
      (BoNT) C1 and D genes, followed by two subsequent PCR amplifications with two
      primer pairs specific for BoNT/C1 and D respectively (198 bp DNA fragment). This
      method was found to be specific for C. botulinum C and D, amongst 81 strains of
      C. botulinum and 21 different species of other Clostridium and bacteria tested.
      The detection limit ranged from 10 to 10(3) bacteria in the reaction volume
      according to the C. botulinum C and D strains. In 160 naturally contaminated
      animal and food samples submitted to a 48 h enrichment culture, the double PCR
      showed an 89.4% correlation rate with the standard mouse bioassay. A clear
      distinction between botulism type C and D was obtained. The double PCR provides a
      reliable alternative for detection and identification of C. botulinum C and D in
      clinical and food samples.

PMID- 8739192
TI  - Ribotyping of Pseudomonas aeruginosa isolates from patients and water springs and
      genome fingerprinting of variants concerning mucoidy.
AB  - Thirty-one strains of Pseudomonas aeruginosa, isolated from water springs,
      clinical isolates (some of which were from cystic fibrosis (CF) patients), and
      two type cultures, were characterized by ribotyping. After restriction of
      chromosomal DNA of the different isolates with EcoRI and hybridization of
      Southern transfer blots with 2-acetylaminofluorene labelled Escherichia coli 16S
      + 23S rRNA probe, eleven different ribopatterns were obtained, representing
      variations of a dominant profile. This largely predominant pattern included both
      type cultures, all six isolates from water springs, 33% of the nine CF isolates
      and 43% of fourteen other clinical isolates most of them from nosocomial
      infections. When the genomic macrorestriction fingerprints of three mucoid CF
      isolates, with Asel, Drai or BfrI were compared with those of their spontaneous
      variants, concerning mucoidy, no differences were detected.

PMID- 8739193
TI  - Effects of murine lysozyme on lipopolysaccharide-induced biological activities.
AB  - We have demonstrated that egg-white lysozyme (EW-LZM) bound to lipopolysaccharide
      (LPS), reduced the lethal toxicity and the biological activity of LPS. In this
      study, the interaction of LPS with murine lysozyme (M-LZM) and the modulation of
      biological activities were investigated. M-LZM was prepared from the culture
      supernatant of the murine macrophage cell line RAW264.7 by ion-exchange and gel
      filtration chromatographies and dialysis. Two types of M-LZM, murine M lysozyme
      (MM-LZM) and murine P lysozyme (MP-LZM), were purified from the supernatant. The
      enzymatic activities of both MM-LZM and MP-LZM were inhibited by LPS and their
      effects were affected by the temperature and the ionic strength. TNF-alpha
      production from RAW264.7 by LPS was inhibited by mixing with MM-LZM and MP-LZM.
      MP-LZM inhibited TNF-alpha production stronger than MM-LZM. Considering these
      facts, we suggested that M-LZM, like EW-LZM, make a complex with LPS to reduce
      the toxicity of LPS together with inhibiting the enzymatic activity.

PMID- 8739194
TI  - Gastrointestinal colonisation of BALB/cA mice by Helicobacter pylori monitored by
      heparin magnetic separation.
AB  - Immunocompetent and immunodeficient BALB/cA mice were fed orally with 10(8)
      colony forming units of 2-day-old spiral or coccoid (12 days old) Helicobacter
      pylori strain NCTC 11637. Immunocompetent BALB/cA mice were also fed orally with
      decreasing numbers of spiral or coccoid forms of H. pylori. The gastrointestinal
      colonisation process was monitored for 34 days post-infection by heparin magnetic
      separation and subsequent enzyme immunoassay (EIA) for the detection of the H.
      pylori cells. Both mice types were colonised with H. pylori. The coccoid form of
      H. pylori gave higher EIA absorbance values and more efficient colonisation in
      the mice than the spiral form. Immunocompetent BALB/cA mice fed with the coccoid
      form of H. pylori exhibited an acute inflammation process in histopathological
      samples from the stomachs. In conclusion, H. pylori can infect both
      immunocompetent as well as immunodeficient BALB/cA mice and coccoids (viable but
      non-culturable) obtained after 12 days of culturing can infect BALB/cA mice.

PMID- 8739195
TI  - A glucocorticoid antagonist, mifepristone affects anti-Candida activity of murine
      neutrophils in the presence of prednisolone in vitro and experimental candidiasis
      of prednisolone-treated mice in vivo.
AB  - The effects of a glucocorticoid-antagonist, mifepristone on the suppressive
      action of prednisolone for anti-Candida activity of murine neutrophils were
      examined. Prednisolone suppressed inhibitory activity of neutrophils to mycelial
      growth of Candida albicans. This suppression was cancelled in the presence of 10(
      7)-10(-6) M of mifepristone in vitro. Corresponding to this in vitro action,
      mifepristone protected prednisolone-treated mice from lethal C. albicans
      infection in vivo. These results suggest that glucocorticoid-induced
      vulnerability to Candida infection may be recovered or normalized by application
      of mifepristone.

PMID- 8739196
TI  - A recombinant Escherichia coli heat-stable enterotoxin b (STb) fusion protein
      eliciting neutralizing antibodies.
AB  - STb is a heat-stable enterotoxin elaborated by enterotoxigenic Escherichia coli
      strains associated with weaning piglets and is responsible for diarrhoea in those
      animals. The maltose binding protein (MBP) of E. coli was used as a carrier for
      STb, a poorly immunogenic molecule. Constructions were produced where the gene
      coding for mature STb toxin (MBP-STb) and a fragment of the gene spanning the
      major epitopic region of STb (AA8-AA30) (MBP-STb2) were fused to malE gene coding
      for MBP. The fusion proteins accumulated in the periplasm and were detected with
      a polyclonal antibody raised against the purified toxin. MBP-STb induced
      secretion in the biological model whereas MBP-STb2 was non-toxic. Immunization of
      rabbits evoked an antibody response to STb for these two fusion proteins.
      However, only MBP-STb elicited antibodies that effectively neutralized the
      toxicity of pure STb toxin as determined in the rat loop assay.

PMID- 8739197
TI  - Restraint stress-induced changes in lymphocyte subsets and the expression of
      adhesion molecules.
AB  - The effect of restraint stress on the distribution of lymphocyte subsets were
      studied in young BALB/c male mice. Loss of whole body weight, a reduction in the
      weights of spleen and lymph nodes, and higher levels of serum corticosterone were
      evident after a single continuous restraint period of 16-18 h. Tissue sections of
      spleens from restrained animals revealed erythrocyte depletion in the contracted
      red pulp. Furthermore, there was a significantly higher proportion of CD4+, but
      not of CD8+, lymphocytes in the spleen. The proportion of the CD4+ subset was
      markedly diminished in peripheral blood, whereas no changes were detected in
      lymph nodes. Restraint resulted in enhanced allogeneic mixed lymphocyte
      reactivity and in altered expression of some CD4+, but not CD8+, splenocyte
      adhesion molecules (CD44, LFA-1 and VLA-4). Removal of circulating
      corticosteroids by surgical adrenalectomy abolished the restraint-induced changes
      in lymphocyte adhesion molecule expression. The findings suggest that the
      observed differences in lymphocytes subset distribution of lymphoid organs may be
      due to changes in the pattern of adhesion molecule expression.

PMID- 8739198
TI  - Endotoxin causes release of alpha-melanocyte-stimulating hormone in normal human
      subjects.
AB  - The neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH), a
      proopiomelanocortin derivative, is a potent modulator of fever, inflammation, and
      other aspects of the acute-phase response. Alpha-MSH concentrations increase in
      rabbit plasma after large doses of endotoxin, but it is not known if changes in
      this potent peptide likewise occur during endotoxemia in humans. The current
      study performed to assess changes in plasma alpha-MSH during the acute
      inflammatory response to endotoxin in normal humans. Alpha-MSH was measured in
      plasma samples obtained over a 5-hour study period in 20 normal human subjects
      given endotoxin. Plasma adrenocorticotropic hormone (ACTH) and tumor necrosis
      factor were also measured at the same time points. Endotoxin administration
      caused fever-related increases in plasma alpha-MSH. Five subjects with a high
      thermal response to endotoxin (> 2.6 degrees C above baseline) showed a 2- to 4
      fold increase in circulating alpha-MSH whereas subjects with low fever (< 2.3
      degrees C) did not. Tumor necrosis factor was detected in all subjects after
      endotoxin, but its peak was significantly less (p < 0.01) in those subjects who
      had substantial increases in alpha-MSH. Plasma ACTH increased in all subjects
      given endotoxin, but unlike its 1-13 derivative alpha-MSH, the increases were not
      commensurate with fever. The data show that challenge with endotoxin causes alpha
      MSH release in normal human subjects with high fever. The positive relationship
      between increases in circulating alpha-MSH and high thermal response together
      with previous evidence from animal studies suggest that the neuropeptide is an
      endogenous modulator of host responses.

PMID- 8739199
TI  - Interleukin-2-induced changes in behavioural, neurotransmitter, and immunological
      parameters in the olfactory bulbectomized rat.
AB  - The macrophage theory of depression proposes that abnormal secretions of the
      macrophage cytokines, an increase in interleukin (IL) 1, and a decrease in IL-2
      may cause depression. The olfactory bulbectomized (OB) rat has been developed as
      an animal model of depression. In the present study, the effects of
      intracerebroventricular administration of IL-2 (10 U) for 7 days on behaviour,
      neurotransmitter concentrations, corticosterone levels, and some immune functions
      were investigated. In the novel environment of the 'open-field' apparatus, the OB
      rat showed increases in ambulation, rearing, grooming, and defaecation scores as
      compared with sham-operated animals. Following IL-2 administration, grooming and
      defaecation were significantly attenuated, while the ambulation and rearing
      scores were unaffected. In the elevated plus-maze, the increase in the time spent
      on the open arms of the maze by the OB animal was normalized by IL-2
      administration. In the brain of untreated OB rats, the concentrations of
      noradrenaline were reduced; IL-2 treatment significantly increased the
      concentrations of noradrenaline and serotonin. After administration of IL-2 for 7
      days, the impairments in the immune functions were also largely reversed in OB
      rats. Thus IL-2 significantly normalized the hyperactivity of mononuclear cells,
      the suppression of lymphocyte proliferation, and the reduction in the monocyte
      percentage in the white blood cell count in the OB rat. The concentrations of
      corticosterone in the serum of the OB rat were significantly reduced, but
      returned to control values following IL-2 treatment. The results suggest that IL
      2 may have modulatory functions on behavioural, neurochemical, hormonal, and
      immunological aspects of the OB rat model of depression.

PMID- 8739200
TI  - A factor in lymph node and spleen induced by restraint stress in mice and rats
      suppresses lymphocyte proliferation.
AB  - Extracts from lymph node and spleen in mice and rats subjected to restraint
      stress significantly suppressed lymphocyte proliferation, but extracts from
      brain, skeletal muscle, and thymus gland had no effect on lymphocyte
      proliferation, suggesting that a suppressive factor for lymphocyte proliferation
      might selectively be induced in lymph node and spleen. Further experiments showed
      that biochemical properties, molecular weight, correlation between suppressive
      factors in serum and in extract of the lymph tissue from stressed animals, and
      control of the generation, all indicated that under the conditions of restraint
      stress and under the control of central nervous system a suppressive factor was
      generated in peripheral lymph tissue and then released into the blood-stream,
      which acted as a strong suppressor of lymphocyte proliferation.

PMID- 8739201
TI  - Lipopolysaccharide-induced Fos expression in hypothalamic nuclei of neonatal
      rats.
AB  - The inability of neonates to fully evoke the acute-phase reaction to infection is
      thought to be due in part to central nervous system immaturity. We used the
      expression of Fos protein to evaluate whether acute-phase reaction deficits in
      neonates may indeed be linked to unresponsiveness of brain regions that mediate
      the responses to infection in adult animals. In this study, we used
      lipopolysaccharide (LPS) as the infectious agent. Rats aged 0-1, 3, 6, 9, 12 and
      15 days were divided into groups treated with low- or high-dose LPS (Escherichia
      coli; 50 and 500 micrograms/kg, respectively, i.p.) or pyrogen-free saline (PFS)
      i.p. Two hours after injection, the animals were deeply anesthetized, sacrificed,
      and their brains removed for Fos immunocytochemistry. Fos-like immunoreactive
      (FLI) neurons in the preoptic area (POA), paraventricular nucleus of the
      hypothalamus (PVN), and organum vasculosum laminae terminalis (OVLT) were
      compared between the treatment and the age groups. The forebrain was devoid of
      FLI neurons in 1-day-old rats, but FLI neurons were present at 3 days of age and
      continued to increase with age until 9 days after birth. There were no
      significant differences between the LPS- and PFS-treated groups until day 12 of
      age. At 12 and 15 days of age, FLI neurons in the PVN, medial preoptic and
      lateral preoptic nuclei, and the area surrounding the OVLT were greater in the
      LPS-treated animals. The expression appeared to be both age- and dose-dependent.
      These observations show that the rat brain structures that participate in the
      mediation of the acute-phase reaction do not become responsive to systemic
      pyrogens until 12 days of age, thus suggesting that insensitivity of the brain to
      pyrogenic agents may be partly responsible for the poor response of neonates to
      infectious agents.

PMID- 8739202
TI  - Polypeptide growth factors in the nucleus: a review of function and
      translocation.
AB  - Conventional wisdom declares that polypeptide growth factors act solely by
      binding to the cell surface and transducing a signal through receptor-mediated
      kinase cascades; following this, they are endocytosed and degraded. Recent
      evidence, however, has demonstrated that several growth factors bind to the cell
      surface and are translocated into the nucleus. Furthermore, these growth factors
      exert biochemical function within the nucleus. Here we review the growth factors
      which translocate to the nucleus and/or exert biochemical function within the
      nucleus, and propose possible translocation mechanisms, including retrograde
      transport from the cell surface to the nuclear envelope.

PMID- 8739203
TI  - Role of the cytokines in the hypothalamic-pituitary-adrenal and gonadal axes.
AB  - Cytokines are soluble mediators of immune function that also regulate several
      endocrine systems. Interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha
      (TNF alpha) each mediate certain aspects of inflammation. In addition, these
      agents regulate hormone secretion from and cellular proliferation within
      endocrine tissues. Thus, IL-1 and IL-6 each affect hormone release from anterior
      pituitary cells (e.g., growth hormone) and inhibit the proliferation of these
      cells. Cytokines are also localized within discrete nuclei of the hypothalamus
      (e.g., IL-1 in the paraventricular nucleus), where they may affect production of
      neuropeptides and biogenic amines (e.g., corticotropin-releasing hormone).
      Similarly, IL-1 and TNF alpha affect granulosa cell steroidogenesis and IL-6
      production. Follicular atresia may either be augmented or inhibited by cytokines
      depending on their ability to regulate cellular apoptosis. Compartmentation of
      cytokines within adrenal tissue (e.g., IL-6 in the zona glomerulosa) allows
      localized effects of these factors on glucocorticoid secretion. Thus, cytokines
      affect via paracrine or autocrine pathways both hormone secretion from, and
      possibly cellular differentiation within, endocrine tissues.

PMID- 8739204
TI  - Effects of N6-cyclopentyladenosine and caffeine on sleep regulation in the rat.
AB  - To study the role of adenosine in sleep regulation, the adenosine A1 receptor
      agonist N6-cyclopentyladenosine (CPA) and the antagonist caffeine were
      administered to rats. Intraperitoneal (i.p.) CPA 1 mg/kg but not 0.1 mg/kg,
      suppressed rapid-eye-movement (REM) sleep and enhanced electroencephalographic
      (EEG) slow-wave activity (power density 0.75-4.0 Hz) in non-REM sleep. The latter
      effect was remarkably similar to the response to 6-h sleep deprivation. The
      effects persisted when CPA-induced hypothermia was prevented. Caffeine (10 and 15
      mg/kg i.p.) elicited a dose-dependent increase in waking followed by a prolonged
      increase of slow-wave activity in non-REM sleep. The combination of caffeine (15
      mg/kg) and sleep deprivation caused less increase in slow-wave activity than
      sleep deprivation alone, indicating that caffeine may reduce the buildup of sleep
      pressure during waking. The results are consistent with the involvement of
      adenosine in the regulation of non-REM sleep.

PMID- 8739205
TI  - Chronic inhibition of intracellular Ca2+ release or protein kinase C activation
      significantly reduces the development of morphine dependence.
AB  - We have previously shown that chronic antagonism of metabotropic glutamate
      receptors in the brain attenuates naloxone-precipitated withdrawal symptoms in
      rats treated chronically with subcutaneous (s.c.) morphine. Several subtypes of
      metabotropic glutamate receptors are directly linked, through a guanine
      nucleotide regulatory protein, to the phosphatidylinositol (p.i.) second
      messenger system. In the present investigation, we assessed the effect of
      inhibiting the products of p.i. hydrolysis on the development of opioid
      dependence. Thus, concurrently with subcutaneous morphine, we infused
      intracerebroventricularly (i.c.v.) in rats, various doses of chelerythrine, which
      selectively inhibits the activation of protein kinase C, and thapsigargin, which
      inhibits the release of intracellular Ca2+ when given chronically. Both
      chelerythrine and thapsigargin reduced the severity of naloxone-precipitated
      abstinence symptoms when infused i.c.v. at a dose of 10 nmol/day. A single
      injection of either chelerythrine or thapsigargin immediately prior to the
      precipitation of withdrawal failed to decrease the severity of abstinence
      symptoms. Our results suggest that by chronically inhibiting activity of the
      phosphatidylinositol system, the development of morphine dependence can be
      attenuated.

PMID- 8739206
TI  - Thyrotropin-releasing hormone facilitates spinal nociceptive responses by
      potentiating NMDA receptor-mediated transmission.
AB  - The interaction of thyrotropin-releasing hormone (TRH) with NMDA receptor
      mediated responses has been investigated in alpha-chloralose-anaesthetized
      spinalized rats with respect to its relevance to spinal nociceptive transmission.
      The effects of TRH and of the uncompetitive NMDA antagonist ketamine were tested
      on responses of dorsal horn wide dynamic range neurones to noxious pinch, heat
      and electrical stimuli in parallel with those to iontophoretically applied N
      methyl-D-aspartate (NMDA) and AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid). Tests with NMDA blocking doses of ketamine (4 mg/kg i.v.)
      demonstrated a variable NMDA receptor-mediated component of all synaptic
      responses. TRH (0.5-1 mg/kg i.v.) enhanced the responses to NMDA (but not AMPA)
      in parallel with an increase of responses to all noxious stimuli and the 'wind
      up' component of the responses to repeated electrical stimulation. This
      potentiation was completely reversed by a subsequent administration of ketamine
      (4 mg/kg i.v.). The results indicate that TRH facilitates nociceptive
      transmission in the spinal dorsal horn via a selective positive modulation of
      NMDA receptor-mediated transmission.

PMID- 8739207
TI  - Na+,K(+)-ATPase activity is selectively increased in thalamus in thiamine
      deficiency prior to the appearance of neurological symptoms.
AB  - The relationship between progression of neurological status and the activities of
      both Na+,K(+)- and Mg(2+)-dependent-ATPase (adenosine 5'-triphosphate
      phosphohydrolase) was investigated in brain regions of pyrithiamine-induced
      thiamine deficient rats. Thalamic Na+,K(+)-ATPase activity was selectively
      increased by 200% (P < 0.01) prior to the appearance of symptoms of thiamine
      deficiency and normalized in symptomatic rats. This selective transitory
      activation precludes a mediation by brain soluble fraction Na+,K(+)-ATPase
      modifiers as does the unaltered distribution in regional high-affinity
      [3H]ouabain binding densities observed throughout the time-course used in these
      experiments. Na+,K(+)-ATPase maintains cellular ionic gradients and has been
      implicated in neurotransmitter uptake and release mechanisms. The fact that the
      increased thalamic Na+,K(+)-ATPase activity coincides with the early alterations
      in serotonin metabolism observed in similarly treated animals and the
      concomitantly early increase in glucose utilization previously observed in the
      thalamus of thiamine-deficient rats is discussed.

PMID- 8739208
TI  - Antidystonic effects of L-type Ca2+ channel antagonists in a hamster model of
      idiopathic dystonia.
AB  - The effects of selective L-type Ca2+ channel antagonists on severity of dystonia
      were investigated in a mutant hamster model of idiopathic generalized dystonia.
      Nimodipine and diltiazem significantly decreased the severity of dystonia.
      Nimodipine was more potent in this respect and did not cause any behavioral side
      effects. The present data therefore suggest that Ca2+ channel antagonists could
      be useful in the treatment of idiopathic dystonia. The antidystonic effect of
      diltiazem and nimodipine may be based on their antidopaminergic action. However,
      the lack of significant effects of the L-type channel agonist (+/-)-BAY k-8644 (1
      5 mg/kg; methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methylphenyl) 
      pyridine-5-carboxylate)) on severity of dystonia may indicate that voltage-gated
      Ca2+ channels are not critically involved in the pathophysiology of dystonia in
      mutant hamsters.

PMID- 8739209
TI  - Effects of zatebradine on ouabain-, two-stage coronary ligation- and epinephrine
      induced ventricular tachyarrhythmias.
AB  - To determine whether a hyperpolarization-activated current (If) participates in
      ventricular tachyarrhythmias, we investigated the effects of zatebradine, an I(f)
      inhibitor, on the ventricular tachyarrhythmias induced by ouabain, two-stage
      coronary ligation and epinephrine infusion in the dog heart. We determined atrial
      rate, ectopic ventricular rate, total heart rate and arrhythmic ratio (the number
      of ectopic ventricular beats divided by total heart beats). Zatebradine (0.15,
      0.5 and 1.5 mg/kg, i.v.) dose dependently decreased the arrhythmic ratio, ectopic
      ventricular rate and atrial rate of the ouabain-induced ventricular
      tachyarrhythmias in pentobarbital-anesthetized dogs. The inhibition by
      zatebradine of the ventricular arrhythmias needed larger doses than the
      inhibition of the atrial rate. Zatebradine weakly depressed the ectopic
      ventricular rate but not the arrhythmic ratio of the ventricular arrhythmias
      induced by two-stage coronary ligation 24 h after the ligation in conscious dogs.
      Although neither the ectopic ventricular rate nor the arrhythmic ratio of the
      epinephrine-induced ventricular arrhythmias was affected by zatebradine, after
      treatment with zatebradine, the arrhythmias elicited by epinephrine developed
      more slowly. Together with the previously reported spectra of the effects of the
      antiarrhythmic agents in three ventricular tachyarrhythmia models, our results
      suggest that zatebradine may improve automaticity-related ventricular
      tachyarrhythmias due to I(f) inhibition or to other undetermined mechanisms in
      the heart.

PMID- 8739210
TI  - Benextramine acts as an irreversible noncompetitive antagonist of U46619-mediated
      contraction of the rat small mesenteric artery.
AB  - We have studied the effects of benextramine on the U46619 (11 alpha,9 alpha
      epoxymethano-15S-hydroxy-prosta-5Z,13E-dienoic acid)-mediated contraction of the
      rat isolated small mesenteric artery. U46619 (10 nM-10 microM) produced a
      concentration-dependent contraction of the small mesenteric artery. The selective
      prostanoid TP receptor antagonist, SQ 30,741 ([1S-[1 alpha,2 alpha(5Z),3 alpha,4
      alpha]]-7- [[[[[(oxaheptyl)amino]acetyl]amino]-methyl]-7-oxabicyclo[2.2.1]hep t-2
      yl]-5- heptenoic acid; 1 microM), produced a parallel, rightward shift of the
      U46619 curve with an associated pA2 value of 7.43 +/- 0.09. Treatment of tissues
      with 100 microM benextramine depressed the maximum response to U46619 in a time
      dependent manner. However, neither SQ 30,741 (10 microM) nor U46619 (10 microM)
      incubation significantly protected against this effect. Thus, benextramine acts
      as an irreversible noncompetitive antagonist of U46619. The mechanism of this
      action is not yet clear.

PMID- 8739211
TI  - Effects of specific tachykinin receptor antagonists on citric acid-induced cough
      and bronchoconstriction in unanesthetized guinea pigs.
AB  - We compared the effects of a tachykinin NK1 receptor antagonist, FK888 (N2-[(4R)
      4-hydroxy-1-(1-methyl-1H-indol-3-yl)carbonyl-L-prolyl]-N-methy l-N -phenylmethyl
      3-(2-naphthyl)-L-alaninamide), and a tachykinin NK2 receptor antagonist, SR48968
      ((S)-N-methyl-N[4-(4-acetylamino-4-phenyl piperidino)-2-(3,4
      dichlorophenyl)butyl]benzamide]), on citric acid-induced cough and
      bronchoconstriction in conscious guinea pigs. FK888 and SR48968 inhibited the
      cough dose dependently. Combination of FK888 and SR48968 showed a small additive
      effect compared with that of FK888 or SR48968 alone. SR48968 but not FK888
      inhibited the bronchoconstriction dose dependently. These results indicate that
      tachykinin NK1 receptors as well as tachykinin NK2 receptors are involved in the
      citric acid-induced cough response. The antitussive activity of the tachykinin
      NK1 receptor antagonist appeared not to depend on the anti-bronchoconstrictor
      effects.

PMID- 8739212
TI  - Contractile responses of human deferential artery and vas deferens to
      vasopressin.
AB  - We studied the effects of vasopressin on isolated rings of human deferential
      artery and vas deferens (prostatic portion) obtained from patients undergoing
      radical cystectomy (n = 11) or prostatectomy (n = 10). Ring segments of artery or
      vas deferens were studied in organ bath experiments at optimal resting tension.
      In artery rings, vasopressin produced concentration-dependent, endothelium
      independent contractions with an EC50 of 4.5 x 10(-10) M. The presence of NG
      nitro-L-arginine methyl ester hydrochloride (10(-4) M), an inhibitor of nitric
      oxide synthase, did not change significantly (P > 0.05) the vasopressin-induced
      contraction. In ring preparations of the prostatic part of the vas deferens,
      vasopressin induced phasic contractions with an EC50 of 7.0 x 10(-9) M. The
      vasopressin V1 receptor antagonist, d(CH2)5Tyr(Me)AVP (10(-8) and 10(-6)),
      displaced to the right in parallel the control curve to vasopressin in artery and
      vas deferens rings. These results indicate that vasopressin exerts a powerful
      constrictor action on human deferential artery and vas deferens by direct
      stimulation of V1 receptors. It is concluded that the deferential artery may
      dampen the passage of blood to the vas deferens in circumstances characterized by
      increased plasma vasopressin levels.

PMID- 8739214
TI  - Neuroprotective effects of RPR 104632, a novel antagonist at the glycine site of
      the NMDA receptor, in vitro.
AB  - The NMDA antagonist and neuroprotective effects of RPR 104632 (2H-1,2,4
      benzothiadiazine-1-dioxide-3-carboxylic acid), a new benzothiadiazine derivative,
      with affinity for the glycine site of the NMDA receptor-channel complex are
      described. RPR 104632 antagonized the binding of [3H]5,7-dichlorokynurenic acid
      to the rat cerebral cortex, with a Ki of 4.9 nM. This effect was stereospecific,
      since the (-)-isomer was 500-fold more potent than the (+)-isomer. The potent
      affinity of RPR 104632 for the glycine site was confirmed by the observation that
      RPR 104632 inhibited [3H]N-[1-(2-thienyl)cyclohexyl]-3,4-piperidine ([3H]TCP)
      binding in the presence of N-methyl-D-aspartate (NMDA) (IC50 = 55 nM), whereas it
      had no effect on the competitive NMDA site or on the dissociative anaesthetic
      site. RPR 104632 inhibited the NMDA-evoked increase in guanosine 3',5'-cyclic
      monophosphate (cGMP) levels of neonatal rat cerebellar slices (IC50 = 890 nM) in
      a non-competitive manner and markedly reduced NMDA-induced neurotoxicity in rat
      hippocampal slices and in cortical primary cell cultures. These results suggest
      that RPR 104632 is a high-affinity specific antagonist of the glycine site
      coupled to the NMDA receptor channel with potent neuroprotective properties in
      vitro.

PMID- 8739213
TI  - N-(2-hydroxyethyl)hexadecanamide is orally active in reducing edema formation and
      inflammatory hyperalgesia by down-modulating mast cell activation.
AB  - Mast cells play a key role in inflammatory reactions triggered by tissue injury
      or immune perturbations. Little is known about endogenous molecules and
      mechanisms capable of modulating inappropriate mast cell activity. N-(2
      Hydroxyethyl)hexadecanamide (palmitoylethanolamide), found in peripheral tissues,
      has been proposed to act as a local autacoid capable of negatively regulating
      mast cell activation and inflammation-hence the acronym Autacoid Local
      Inflammation Antagonism (ALIA). Recently, N-(2-hydroxyethyl)hexadecanamide (LG
      2110/1) has been reported to down-modulate mast cell activation in vitro by
      behaving as an agonist at the peripheral cannabinoid CB2 receptor. Here, we have
      characterized and functionally correlated the anti-inflammatory actions of LG
      2110/1 with its ability to control mast cell activation, when given orally in a
      battery of rodent models of inflammation. LG 2110/1 diminished, in a dose
      dependent and correllated manner, the number of degranulated mast cells and
      plasma extravasation induced by substance P injection in the mouse ear pinna. In
      addition, LG 2110/1 reduced dose dependently plasma extravasation induced by
      passive cutaneous anaphylaxis reaction. In adult rats LG 2110/1 decreased, in a
      dose-dependent manner, carrageenan-induced hindpaw edema and hyperalgesia, but
      not phospholipase A2-induced hindpaw edema. Further, anti-edema effects were
      observed when utilizing dextran and formalin, known to also cause mast cell
      activation. Locally administered LG 2110/1 was likewise effective in minimizing
      dextran-induced hind paw edema. In contrast, equivalent amounts of palmitic acid
      plus ethanolamine were ineffective against plasma extravasation provoked by
      substance P. LG 2110/1 did not decrease plasma extravasation induced by the
      substance P fragment, substance P-(6-11), known to be inactive on mast cells.
      These results indicate that orally administered N-(2-hydroxyethyl)hexadecanamide
      is effective in: (a) directly down-modulating mast cell activation in vivo; (b)
      suppressing pathological consequences initiated by mast cell activation
      independently of the activating stimuli; (c) exerting an anti-inflammatory action
      distinguishable from that of classical steroidal and non-steroidal anti
      inflammatory agents. These findings raise the possibility that N-(2
      hydroxyethyl)hexadecanamide and related saturated N-acylamides ('ALIAmides')
      represent novel therapeutic agents useful in the management of inflammatory
      disease conditions.

PMID- 8739215
TI  - Effects of 17 beta-estradiol and progesterone on mitogen-activated protein kinase
      expression and activity in rat uterine smooth muscle.
AB  - Activation of mitogen-activated protein kinases (MAPKs) is a critical event in
      mitogenic signal transduction. MAPKs are activated by tyrosine phosphorylation
      and translocate to different cellular compartments affecting protein function and
      gene expression. MAPK expression and activity was examined in uterine smooth
      muscle from rats pretreated with estradiol-17 beta alone or with estradiol-17
      beta and progesterone. MAPK expression was detected by immunoblotting using
      erk1/2 antibodies. MAPK activity was detected by measurement of the
      phosphorylation of a MAPK-specific peptide sequence of myelin basic protein.
      Steroid treatment caused a modest (20%) decline in erk 1 and 2 expression in
      membrane and cytosolic fractions. Both estrogen and progesterone increased MAPK
      tyrosine phosphorylation and membrane-associated MAPK activity. Steroid treatment
      increased cytosolic MAPK tyrosine phosphorylation, but not enzymatic activity.
      These data suggest that gonadal steroid hormones, which stimulate uterine
      hypertrophy, may exert their hypertrophic effects by increasing MAPK activity.

PMID- 8739216
TI  - Effects of prostaglandins and cyclic AMP on cytokine production in rat
      leukocytes.
AB  - Prostaglandins E1, prostaglandin E2, 3-oxa-methano-prostaglandin I1 (SM-10906), a
      stable prostaglandin I2 analog, and dibutyryl cyclic AMP suppressed the
      production of tumor necrosis factor and interleukin-1 in lipopolysaccharide
      stimulated rat pleural resident monocytic cells, whereas they enhanced the
      production of interleukin-6 and cytokine-induced neutrophil chemoattractant
      (CINC), a rat interleukin-8-like chemokine, in these cells. SM-10906 also
      inhibited the in vivo production of tumor necrosis factor and interleukin-1 in
      pleural exudates, when injected into the rat pleural cavity concomitantly with
      carrageenin. The cyclic AMP (cAMP) level in the lipopolysaccharide-stimulated
      resident cells was increased when the cells were incubated in the presence of
      prostaglandin E1, prostaglandin E2 or SM-10906. Prostaglandin I2 showed only
      slight effects. The addition of pentoxifylline, a phosphodiesterase inhibitor, to
      the incubation mixture increased the cAMP level and also enhanced the effect of
      prostaglandins, indicating that these regulating actions of prostaglandins may be
      exerted partly through a mechanism involving an increased intracellular cAMP
      level.

PMID- 8739217
TI  - Rat striatum contains pure population of ETB receptors.
AB  - In most organs of the body, endothelin acts on endothelin ETA and ETB receptors
      that co-exist (albeit often on different cell types). Although virtually pure
      endothelin ETA receptors have been identified in some tissues (e.g., lung), no
      essentially pure endothelin ETB receptor tissue has been reported to date.
      [125I]Endothelin-1 bound to striatal membrane preparations with a Kd of 19.4 +/-
      0.2 pM and Bmax of 496 +/- 8 fmol/mg protein. Endothelin-1 displaced
      [125I]endothelin-1 receptor binding with an IC50 of 23 pM. The endothelin ETB
      selective antagonist BQ788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma -methyl
      leucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine) and agonist sarafotoxin 6C
      displaced [125I]endothelin-1 monophasically with IC50 values of 25 nM and 110 pM,
      respectively, whereas that of the endothelin ETA-selective antagonist BQ123
      (cyclo(D-Trp-D-Asp-Pro-D-Val-Leu)) was 24 microM, values agreeing with cloned
      human endothelin ETB but not ETA receptors. Receptor autoradiography confirmed
      that rat striatum (but not white matter) contains essentially exclusively
      endothelin ETB receptors.

PMID- 8739218
TI  - Differences in microcirculatory bed arrangement in some skeletal muscles of the
      rat and golden hamster.
AB  - The architectural features of the most peripheral parts of the microcirculatory
      bed were studied in selected skeletal muscles (cremaster, retractor,
      spinotrapezius, and ventral stripe of spinotrapezius) in rats and golden hamsters
      ranging in weight between 130 and 330 and 130 and 180 g, respectively. In the
      cremaster muscle of both species, a very complicated, irregular and heterogenous
      arrangement of terminal arterioles, as well as of postcapillary and collecting
      venules was found. In the retractor, the most regular arrangement was along the
      margins of the middle part of muscle, but an irregular brush-like branching of
      the terminal arterioles and collecting venules limits the use of these areas.
      Similarly, in spinotrapezius muscle the most regular vascular architecture,
      complicated by a different fashion of terminal arterioles and collecting venules,
      was along the ventral border of muscle. The most regular and simplest vascular
      arrangement was in the ventral stripe of spinotrapezius of the rat. Therefore,
      this muscle is recommended as most appropriate for intravital experimental
      studies of the skeletal muscle microcirculatory bed in all age and weight groups.

PMID- 8739219
TI  - Basic-fibroblast-growth-factor-mediated de novo angiogenesis is more effectively
      suppressed by low-molecular-weight than by high-molecular-weight heparin.
AB  - We recently reported that the subcutaneous (s.c.) administration of a low
      molecular-weight heparin (LMWH) fraction significantly inhibited de novo
      angiogenesis in the mesentery induced by the intraperitoneal (i.p.) injection of
      saline to adult rats compared with unfractionated heparin and high-molecular
      weight heparin (HMWH) fractions. The present study assesses the effect on basic
      fibroblast growth factor (bFGF)-mediated de novo angiogenesis in the mesentery of
      the systemic administration of a LMWH fraction (2.6 kD) and a series of four HMWH
      fractions (about 20 kD) with varying degrees of polydispersity, charge density
      and anticoagulant activity. bFGF, a prototypic heparin-binding angiogenic growth
      factor, was injected i.p. at 220 pM on days 0-4. The heparins were given s.c. on
      days 0-13 or 0-14 at doses which were approximately within the range used
      clinically. Angiogenesis was assessed by microscopic morphometry and image
      analysis in groups of animals killed on days 14 and 15. Compared with the saline
      control, the LMWH and three of the HMWHs significantly inhibited angiogenesis in
      terms of microvascular length (MVL), a measure of microvascular density.
      Interestingly, the vascularized area (VA), a measure of microvascular spatial
      extension, and the total microvascular length (VA x MVL) were significantly lower
      in the LMWH-treated animals than in the animals treated with one of the HMWHs.
      The total microvascular length was, moreover, significantly reduced in the LMWH
      treated animals compared with the combined data of all the HMWH-treated animals.
      No significant effects were related to the degree of charge density and
      anticoagulant activity of the heparins. In view of the putative significant
      angiogenic role of bFGF in human angiogenesis diseases, the present findings may
      have implications for the choice of anticoagulant treatment modality for patients
      suffering from cancer and other angiogenesis diseases.

PMID- 8739220
TI  - A new technique for controlling the finger skin temperature in microcirculatory
      research demonstrated in a local cold stress test in healthy controls and
      patients with Raynaud's phenomenon.
AB  - Changes in skin temperature cause great changes in blood flow and capillary blood
      pressure. The new technique presented here makes it possible to control the
      temperature of the finger during nailfold capillaroscopy. Automatic temperature
      control, both for warming and cooling, is made possible with the aid of a
      temperature-controlled finger holder. The temperature of the finger holder can be
      automatically matched to the spontaneous skin temperature of the examined finger,
      or the finger holder temperature and temperature change velocity can be set
      digitally to a desired value. We used this new technique in a local cold stress
      test on 9 healthy controls (3 men, 6 women) and 9 patients (3 men, 6 women) with
      Raynaud's phenomenon due to systemic sclerosis. We simultaneously measured
      capillary red blood cell velocity (CBV) and laser Doppler flux (LDF) in adjacent
      areas of the finger nailfold with three different cooling procedures (8, 10, 12
      degrees C for 5 min). CBV and LDF values showed the most pronounced differences
      between patients and controls at 12 degrees C. This new technique supplements
      capillaroscopy with full temperature control and defined temperature changes. It
      can also be combined with measurements of LDF and capillary blood pressure. In
      view of the disadvantages of other cooling methods we recommend this new and easy
      to-handle technique for clinical practice and research.

PMID- 8739221
TI  - Repeatability of intravital capillaroscopic measurement of capillary density.
AB  - The reliability of intravital capillaroscopy for determining capillary density
      (CD) of skin has been questioned because it depends upon the variability of the
      measuring process and subjective interpretation of data as well as the intrinsic
      heterogeneity of capillary spacing. The aim of this study was to assess the
      repeatability of a standardised method for measuring CD of the skin of the dorsum
      of foot. In each of 30 subjects (10 controls and 20 patients with peripheral
      vascular disease), the foot was systematically mapped by examining 20 sites on
      the dorsum of foot and 2 sites on each toe, using white light (native)
      videomicroscopy at 40 x magnification. Off-line analysis of videoprints was then
      undertaken to determine CD at each site, by counting capillaries within areas of
      acceptable photographic quality only, having first defined the criteria for
      counting capillaries. The mean values were then calculated and taken to represent
      the CD of the foot or toes. Repeatability of the measuring equipment was first
      assessed by noting the presence or absence of each corresponding capillary in 2
      prints, taken at intervals of hours or days (in 10 subjects) or months (in 2
      patients), of an identical area of skin which was marked by a microtattoo on the
      first occasion. On average, 95% of corresponding capillaries were identified in
      both prints (from controls and patients), thus implying little intrinsic temporal
      variation of capillary anatomy as well as excellent repeatability of the
      measuring equipment. Repeatability of data analysis was assessed by the same
      observer reading the same 20 prints in a blinded manner on three separate
      occasions (intraobserver repeatability), and 2 observers reading the same 24
      prints (interobserver repeatability). The mean coefficient of intraobserver
      variation of CD estimate was 5.6% and the interobserver correlation coefficient
      was 0.94. Finally, overall repeatability of the method was assessed by repeating
      the procedure on a subsequent occasion (mean time interval of 5 days) in 10
      subjects. The rate of agreement in mean CD between the two procedures [defined as
      100- (difference between the two measurements/mean of the two measurements) x
      100]% ranged from 86.4 to 97.1% (mean 93.5%). Thus using the above methodological
      technique, native capillaroscopy can be reliably used to determine CD of the
      dorsum of foot in comparing patient subgroups, as well as in longitudinal
      studies.

PMID- 8739222
TI  - Effects of iloprost on skin microcirculation.

PMID- 8739223
TI  - Phosphoinositide-generated messengers in cardiac signal transduction.
AB  - A multitude of agonists like e.g. endothelin-1, angiotensin-II, serotonin,
      thrombin, histamine and vasopressin as well as alpha 1-adrenergic and muscarinic
      stimulation lead to stimulation of the phosphoinositide cycle in the heart.
      Besides the seven membrane spanning-domain receptor-coupled stimulation of the
      key enzyme of the phosphoinositide cycle, phospholipase C-beta, another class of
      hormones, growth factors, also couple to the phosphoinositide cycle, now through
      receptors with intrinsic tyrosine kinase activity that can phosphorylate and
      stimulate the phospholipase C-gamma isozyme. In this review we summarize the
      multitude of receptor (sub)types, G-protein-subunit- and phospholipase C-isozymes
      that are present in the heart. Furthermore, generation of second messengers and
      cellular responses are described together with the (patho)physiological
      implications for the heart of phosphoinositide cycle activation and second
      messenger accumulation.

PMID- 8739224
TI  - Angiotensin II signalling pathways in cardiac fibroblasts: conventional versus
      novel mechanisms in mediating cardiac growth and function.
AB  - Angiotensin II has been demonstrated to be involved in the regulation of cellular
      growth of several tissues in response to developmental, physiological, and
      pathophysiological processes. Angiotensin II has been implicated in the
      developmental growth of the left ventricle in the neonate and remodeling of the
      heart following chronic hypertension and myocardial infarction. The inhibition of
      DNA synthesis and collagen deposition in myocardial interstitium following
      myocardial infarction by angiotensin converting enzyme inhibitor, suggests that
      angiotensin II mediates interstitial and perivascular fibrobrosis by preventing
      fibroblast proliferation. In the past, little attention was focused on the
      identity and functional roles of cardiac fibroblasts. Recent in vitro studies
      utilizing cultured cardiac fibroblasts demonstrate that angiotensin II, acting
      via the AT1 receptor, initiates intracellular signalling pathways in common with
      those of peptide growth factors. Below, we describe growth-related aspects of
      cardiac fibroblasts with respect to angiotensin II receptors, conventional and
      novel signal transduction systems, secretion of extracellular matrix proteins and
      growth factors, and localization of renin-angiotensin system components.

PMID- 8739225
TI  - Signalling by cGMP-dependent protein kinases.
AB  - The second messenger cGMP is a major intracellular mediator of the vaso-active
      agents nitric oxide and natriuretic peptides. The principal targets of cGMP are
      (i) phosphodiesterases, resulting in interference with the cAMP-signalling
      pathway, (ii) cGMP-gated cation channels, and (iii) cGMP-dependent protein
      kinases (cGKs). Only two mammalian isotypes of cGK have been described so far:
      type I cGK, consisting of an alpha and a beta isoform, presumably splice variants
      of a single gene, and identified as the most prominent cGK isotype in the cardio
      vascular system; and type II cGK, expressed mainly in the intestine, the kidney
      and the brain. High levels of cGK I are found in vascular smooth muscle cells,
      endothelial cells and platelets. In these cells, cGK I is thought to counteract
      the increase in contraction provoked by Ca-mobilizing agonists, to reduce
      endothelial permeability and to inhibit platelet aggregation, respectively.
      Relatively low levels of cGK I are found in cardiomyocytes. In this cell type,
      cGK is implicated in the negative inotropic effect of cGMP, presumably through
      modulation of Ca channels and by diminishing the Ca-sensitivity of contractile
      proteins.

PMID- 8739226
TI  - Regulation of G protein function: implications for heart disease.
AB  - Heterotrimeric GTP-binding and -hydrolyzing proteins (G proteins) link members of
      a family of seven-helix transmembrane receptors (G protein-coupled receptors,
      GPCR) to intracellular effectors. The coupling mechanism involves the G protein
      completing a cycle of activation, dissociation into alpha and beta gamma
      subunits, deactivation, and reassociation. At the center of this cycle is the
      alpha subunit, in which activation by GPCR, GTPase activity, and regulation of
      effector are combined. Whereas G alpha's functional domains and residues had
      already been inferred from mutagenesis studies, the recent solution of the
      crystal structure has elucidated the structural basis of alpha subunit function.
      It is now clear that an irregularity in any GPCR pathway component could cause a
      physiological defect. This is confirmed by the identification of mutations in
      GPCR and G alpha's in various human diseases. Although several cardiomyopathies
      are associated with abnormal GPCR function, mutations are unlikely in these
      disorders. The last few years, other aspects of G protein function have moved
      into focus: e.g. posttranslational modifications; effector regulation by beta
      gamma subunits; GTPase activating protein (GAP) activity of effectors; G protein
      expression levels etc. When comparing the regulation of G protein functional
      activity in cAMP and in inositol phosphate generating pathways, an extrapolation
      can be made to data on the status of these pathways in some cardiovascular
      diseases.

PMID- 8739227
TI  - Regulation and functional significance of phospholipase D in myocardium.
AB  - There is now clear evidence that receptor-dependent phospholipase D is present in
      myocardium. This novel signal transduction pathway provides an alternative source
      of 1,2-diacylglycerol, which activates isoforms of protein kinase C. The members
      of the protein kinase C family respond differently to various combinations of
      Ca2+, phosphatidylserine, molecular species of 1,2-diacylglycerol and other
      membrane phospholipid metabolites including free fatty acids. Protein kinase C
      isozymes are responsible for phosphorylation of specific cardiac substrate
      proteins that may be involved in regulation of cardiac contractility,
      hypertrophic growth, gene expression, ischemic preconditioning and
      electrophysiological changes. The initial product of phospholipase D,
      phosphatidic acid, may also have a second messenger role. As in other tissues,
      the question how the activity of phospholipase D is controlled by agonists in
      myocardium is controversial. Agonists, such as endothelin-1, atrial natriuretic
      factor and angiotensin II that are shown to activate phospholipase D, also
      potently stimulate phospholipase C-beta in myocardium. PMA stimulation of protein
      kinase C inactivates phospholipase C and strongly activates phospholipase D and
      this is probably a major mechanism by which agonists that promote phosphatidyl
      4,5-bisphosphate hydrolysis secondary activate phosphatidylcholine-hydrolysis. On
      the other hand, one group has postulated that formation of phosphatidic acid
      secondary activates phosphatidyl-4,5-bisphosphate hydrolysis in cardiomyocytes.
      Whether GTP-binding proteins directly control phospholipase D is not clearly
      established in myocardium. Phospholipase D activation may also be mediated by an
      increase in cytosolic free Ca2+ or by tyrosine-phosphorylation.

PMID- 8739228
TI  - Mitogen-activated protein kinase (MAPK) in cardiac tissues.
AB  - Mitogen-activated protein kinase (MAPK) has recently emerged as a prominent role
      player in intracellular signalling in the ventricular myocyte with attention
      being focussed on its possible role in the development of ventricular
      hypertrophy. It is becoming clear that MAPK is also active in other cells of
      cardiac origin such as cardiac fibroblasts and possible functions of this
      signalling pathway in the heart have yet to be explored. In this report the
      mammalian MAPK pathway is briefly outlined, before reviewing current knowledge of
      the MAPK pathway in cardiac tissue (ventricular myocytes, vascular smooth muscle
      cells and cardiac fibroblasts). New data is also presented on the presence and
      activity of MAPK in two additional cardiac celltypes namely atrial myocytes and
      vascular endothelial cells from the coronary microcirculation.

PMID- 8739229
TI  - Phosphotransfer reactions as a means of G protein activation.
AB  - Heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) serve
      to transduce information from agonist-bound receptors to effector enzymes or ion
      channels. Current models of G protein activation-deactivation indicate that the
      oligomeric GDP-bound form must undergo release of GDP, bind GTP and undergo
      subunit dissociation, in order to be in active form (GTP bound alpha subunits and
      free beta gamma dimers) and to regulate effectors. The effect of receptor
      occupation by an agonist is generally accepted to be promotion of guanine
      nucleotide exchange thus allowing activation of the G protein. Recent studies
      indicate that transphosphorylation leading to the formation of GTP from GDP and
      ATP in the close vicinity, or even at the G protein, catalysed by membrane
      associated nucleoside diphosphate kinase, may further activate G proteins. This
      activation is demonstrated by a decreased affinity of G protein-coupled receptors
      for agonists and an increased response of G protein coupled effectors. In
      addition, a phosphorylation of G protein beta subunits and consequent phosphate
      transfer reaction resulting in G protein activation has also been demonstrated.
      Finally, endogenously formed GTP was preferentially effective in activating some
      G proteins compared to exogenous GTP. The aim of this report is to present an
      overview of the evidence to date for a transphosphorylation as a means of G
      protein activation (see also refs [1 and 2] for reviews).

PMID- 8739231
TI  - Nitric oxide--a retrograde messenger for carbon monoxide signaling in ischemic
      heart.
AB  - To examine the intracellular signaling mechanism of NO in ischemic myocardium,
      isolated working rat hearts were made ischemic for 30 min followed by 30 min of
      reperfusion. A separate group of hearts were pre-perfused with 3 mM L-arginine in
      the presence or absence of 650 microM of protoporphyrin, a heme oxygenase
      inhibitor for 10 min prior to ischemia. The release of NO was monitored using an
      on-line amperometric sensor placed into the right atrium. The aortic flow and
      developed pressure were examined to determine the effects of L-arginine on
      ischemic/reperfusion injury. Induction for the expression of heme oxygenase was
      studied by Northern hybridization. For signal transduction experiments,
      sarcolemmal membranes were radiolabeled by perfusing the isolated hearts with
      [3H] myoinositol and [14C] arachidonic acid. Biopsies were processed to determine
      the isotopic incorporation into various phosphoinositols as well as phosphatidic
      acid and diacylglycerol. cGMP was assayed by radioimmunoassay and SOD content was
      determined by enzymatic analysis. The release of NO was diminished following
      ischemia and reperfusion and was augmented by L-arginine. L-arginine reduced
      ischemic/reperfusion injury as evidenced by the enhanced myocardial functional
      recovery. Protoporphyrin modulated the effects of L-arginine. cGMP, which was
      remained unaffected by ischemia and reperfusion, was stimulated significantly
      after L-arginine treatment. The NO-mediated augmentation of cGMP was reduced by
      protoporphyrin suggesting that part of the effects may be mediated by CO
      generated through the heme oxygenase pathway. Reperfusion of ischemic myocardium
      resulted in significant accumulation of radiolabeled inositol phosphate, inositol
      bisphosphate, and inositol triphosphate. Isotopic incorporation of [3H] inositol
      into phosphatidylinositol, phosphatidylinositol-4-phosphate, and
      phosphatidylinositol-4,5-bisphosphate was increased significantly during
      reperfusion. Reperfusion of the ischemic heart prelabeled with [14C] arachidonic
      acid resulted in modest increases in [14C] diacylglycerol and [14C] phosphatidic
      acid. Pretreatment of the heart with L-arginine significantly reversed this
      enhanced phosphodiesteratic breakdown during ischemia and early reperfusion.
      However, at the end of the reperfusion the inhibitory effect of L-arginine on the
      phosphodiesterases seems to be reduced. In L-arginine treated hearts, SOD
      activity was progressively decreased with the duration of reperfusion time. The
      results suggests for the first time that NO plays a significant role in
      transmembrane signaling in the ischemic myocardium. This signaling appears to be
      on- and off- nature, and linked with SOD content of the tissue. The signaling is
      transmitted via cGMP and opposes the effects of phosphodiesterases by inhibiting
      the ischemia/reperfusion-induced phosphodiesteratic breakdown. Our results also
      suggest that NO activates heme oxygenase which further stimulates the production
      of cGMP presumably by CO signaling. Thus, NO not only potentiates cGMP mediated
      intracellular signaling, it also functions as a retrograde messenger for CO
      signaling in heart.

PMID- 8739230
TI  - Signalling by protein kinase C isoforms in the heart.
AB  - Understanding transmembrane signalling process is one of the major challenge of
      the decade. In most tissues, since Fisher and Krebs's discovery in the 1950's,
      protein phosphorylation has been widely recognized as a key event of this
      cellular function. Indeed, binding of hormones or neurotransmitters to specific
      membrane receptors leads to the generation of cytosoluble second messengers which
      in turn activate a specific protein kinase. Numerous protein kinases have been so
      far identified and roughly classified into two groups, namely serine/threonine
      and tyrosine kinases on the basis of the target acid although some more recently
      discovered kinases like MEK (or MAP kinase kinase) phosphorylate both serine and
      tyrosine residues. Protein kinase C is a serine/threonine kinase that was first
      described by Takai et al. [1] as a Ca- and phospholipid-dependent protein kinase.
      Later on, Kuo et al. [2] found that PKC was expressed in most tissues including
      the heart. The field of investigation became more complicated when it was found
      that the kinase is not a single molecular entity and that several isoforms exist.
      At present, 12 PKC isoforms and other PKC-related kinases [3] were identified in
      mammalian tissues. These are classified into three groups. (1) the Ca-activated
      alpha-, beta-, and gamma-PKCs which display a Ca-binding site (C2); (2) the Ca
      insensitive delta-, epsilon-, theta-, eta-, and mu-PKCs. The kinases that belong
      to both of these groups display two cysteine-rich domains (C1) which bind phorbol
      esters (for recent review on PKC structure, see [4]). (3) The third group was
      named atypical PKCs and include zeta, lambda, and tau-PKCs that lack both the C2
      and one cysteine-rich domain. Consequently, these isoforms are Ca-insensitive and
      cannot be activated by phorbol esters [5]. In the heart, evidence that multiple
      PKC isoforms exist was first provided by Kosaka et at. [6] who identified by
      chromatography at least two PKC-related isoenzymes. Numerous studies were thus
      devoted to the biochemical characterization of these isoenzymes (see [7] for
      review on cardiac PKCs) as well as to the identification of their substrates.
      This overview aims at updating the present knowledge on the expression,
      activation and functions of PKC isoforms in cardiac cells.

PMID- 8739232
TI  - Expression of cardiac muscle markers in rat myocyte cell lines.
AB  - Recently developed rat heart myocyte cell lines have afforded us the opportunity
      to evaluate the expression of several transcription factors associated with early
      cardiac development. These factors include, but are not limited to, Nkx-2.5/Csx,
      MEF-2C and MLP (Muscle LIM Protein). These factors have been shown to be
      temporally expressed in pre-cardiac mesenchyme coincident with the earliest
      stages of heart development. Using the BWEM and CLEM myocyte cell lines as models
      of the embryonic, committed cardiomyocyte, we have evaluated the basal expression
      levels of these three genes over multiple passages. Both cell lines express these
      genes, with MEF-2C being the most abundant based on Northern blot hybridization
      analyses. Interestingly, as these cells increased their passage number, there was
      a corresponding increase in their basal expression levels. To evaluate potential
      'downstream' effectors of these genes, we examined the basal expression levels of
      two cardiac-specific genes cTNC and MLC-2v. Transcript levels for both of these
      contractile filament genes were elevated with passage, suggestive of a inductive
      process mediated by one or all these three transcription factors. Promoter
      analysis of MLC-2v expression in the CLEM line shows that this increase is
      transcriptionally-mediated and the lines retain the necessary regulatory factors
      to maintain and control the transcription of this gene. Analysis of the dynamics
      of the regulatory role(s) that these three transcription factors play in cardiac
      development can now be evaluated in a homogeneous, cell culture system.

PMID- 8739233
TI  - Regulation of cardiac gap junction channel permeability and conductance by
      several phosphorylating conditions.
AB  - Short term (15 min) effects of activators of protein kinase A (PKA), PKC and PKG
      on cardiac macroscopic (g(j)) and single channel (gamma j) gap junctional
      conductances were studied in pairs of neonatal rat cardiomyocytes. Under dual
      whole-cell voltage-clamp, PKC activation by 100 nM TPA increased g(j) by 16 +/-
      2% (mean +/- S.E.M, n = 9), 1.5 mM of the PKG activator 8-bromo-cGMP (8Br-cGMP)
      decreased g(j) by 26 +/- 2% (n = 4), whereas 1.5 mM of the PKA activator 8Br-cAMP
      did not affect g(j) (1 +/- 5%, n = 11). Single cardiac gap junction channel
      events, resolved in the presence of heptanol, indicated two gamma j sizes of 20
      pS and 40-45 pS. Under control conditions, the larger events were most frequently
      observed. Whereas 8Br-cAMP did not change this distribution, TPA or 8Br-cGMP
      shifted the gamma j distribution to the lower sizes. Diffusion of 6
      carboxyfluorescein (6-CF), a gap junction permeant tracer, from the injected cell
      to neighboring cells was studied on small clusters of neonatal rat
      cardiomyocytes. Under control conditions, 6-CF labeled 8.4 +/- 0.4 cells (mean +/
      S.E.M, n = 31). Whereas 8Br-cAMP did not change the extent of dye transfer (8.1
      +/- 0.5 cells, n = 10), TPA restricted the diffusion of 6-CF to 2.2 +/- 0.2 cells
      (n = 30) and 8Br-cGMP to 3.5 +/- 0.3 cells (n = 10). This suggests that
      permeability and single channel conductance of Cx43 gap junction channels are
      parallel related. Altogether, these results point to the differential modulation
      of electrical and metabolic coupling of cardiac cells by various phosphorylating
      conditions.

PMID- 8739234
TI  - The transphosphatidylation activity of phospholipase D.
AB  - Transphosphatidylation activity is a characteristic and remarkable property of
      phospholipase D (PLD) and has been studied in plants and mammalian tissues. This
      reaction is often used to confirm the properties and/or abnormalities of PLD
      activity. The mechanism for activating PLD transphosphatidylation seems multiple.
      Although significant changes of transphosphatidylation activity have been found
      in some pathological animal models, the biological significance of PLD
      transphosphatidylation remains largely unknown.

PMID- 8739235
TI  - Reduction in Gh protein expression is associated with cytodifferentiation of
      vascular smooth muscle cells.
AB  - Gh, a high molecular weight GTP-binding protein that couples alpha 1
      adrenoceptors in heart and liver to phosphatidylinositol (PtdIns)-specific
      phospholipase C (PLC), has recently been shown to be a tissue transglutaminase
      type II. Transglutaminases have been suggested to play a role in the maintenance
      of blood vessel structure, and therefore it is possible that changes in their
      expression may accompany pathological states which involve phenotypic modulation
      of smooth muscle. Hence, we investigated the expression of Gh during
      differentiation of rat aortic smooth muscle cells in culture. Gh content was
      reduced markedly in cultured smooth muscle cells compared to freshly isolated
      cells as determined by Western blotting using a Gh-specific monoclonal antibody.
      In contrast, the level of Gq, a heterotrimeric G-protein that couples alpha 1
      adrenoceptors to PLC, was maintained throughout the culture period. These
      findings indicate that changes in Gh expression accompany phenotypic modulation
      of vascular smooth muscle cells. These changes in Gh protein expression may be
      important in the altered responsiveness of vessels in pathological disease
      states.

PMID- 8739236
TI  - Coordinated expression of heme oxygenase-1 and ubiquitin in the porcine heart
      subjected to ischemia and reperfusion.
AB  - Heme oxygenase (HO) isozymes, HO-1 and HO-2 catalyze the cleavage of heme b to
      form the antioxidant biliverdin IXa, iron and the putative cellular messenger
      carbon monoxide (CO). Heat and stress have been reported to induce the expression
      of HO-1, in analogy to ubiquitin, a protein of 8 kDa involved in ATP dependent
      proteolysis. Earlier, we have shown in anesthetized pigs that brief periods of
      coronary artery occlusion followed by reperfusion produce prolonged regional
      cardiac dysfunction (stunning) associated with altered expression of a number of
      genes. In the present study, we report on a coordinated expression pattern of HO
      1 and ubiquitin in the same porcine model in which the left anterior descending
      coronary artery (LAD) was occluded for 10 min and reperfused for 30 min (group I)
      and after a second occlusion of 10 min, reperfused for either 30 min (group II)
      or 90 min (group III) or 210 min (group IV). Myocardial tissue from LAD (stunned)
      and left circumflex coronary artery (LCx, control) perfused regions were
      collected in liquid nitrogen and analysed by Northern and dot blot hybridization
      techniques. We demonstrated a basal myocardial expression of multiple mRNAs
      (monomer and polymers) encoding ubiquitin and a single mRNA species (1.8 kb)
      encoding HO-1. However, the expression of both genes was drastically enhanced in
      the stunned myocardium as compared to the control in groups II and III with
      maximum mRNAs levels in group II. These results suggest that the myocardial
      adaptive response to ischemia involves the coordinated induction of HO-1 and
      ubiquitin, which may be indicative for the existence of a pathophysiologically
      important defense mechanism whereby, both degradation of denatured cellular
      proteins and generation of biologically active products of heme metabolism are
      accelerated.

PMID- 8739237
TI  - Sympathetic control of cardiac myosin heavy chain gene expression.
AB  - Several neuroendocrine factors have been shown to influence the muscle phenotype.
      Various physiological reports have suggested the role of adrenergic nervous
      system for cardiac myosin heavy chain (MHC) expression. We have used cultured
      fetal rat heart myocytes to investigate the role of cAMP on the alpha- and beta
      MHC gene expression. In low density cultures, addition of 1 mM 8 Br cAMP resulted
      in up regulation of alpha-MHC and down regulation of beta-MHC mRNA. This
      antithetic effect of cAMP depends on the basal expression of both expression of
      both MHC transcripts. In transient transfection analysis employing a series of
      alpha-MHC gene promoter/reporter constructs, we identified a 13 bp E-box M-CAT
      hybrid motif (EM element) which conferred a basal muscle specific and cAMP
      inducible expression of the alpha-MHC gene. Data obtained from the mobility gel
      shift analysis indicated that one of the factor(s) binding to the EM element is
      related to troponin T M-CAT binding factor (TEF-1). To test whether the protein
      binding to this sequence could be a substrate for cAMP-dependent phosphorylation,
      the cardiac nuclear proteins were preincubated in a kinase reaction buffer either
      with a catalytic subunit of PKA (CatPKA) or with cAMP, and binding activity of
      proteins to the EM element was evaluated by mobility gel shift assay. In a
      concentration dependent manner, a twofold increase in the intensity of the
      retarded band was observed. Furthermore, at 100 units of CatPKA, an additional
      band of faster mobility was observed which was not present either when
      phosphorylated nuclear extract was incubated with alkaline phosphatase or when
      ATP was absent in kinase reaction buffer. These results strongly suggest that
      factor(s) binding to the EM element is a substrate for cAMP dependent
      phosphorylation.

PMID- 8739238
TI  - Regulation of expression of cardiac sarcoplasmic reticulum proteins under
      pathophysiological conditions.
AB  - Congestive heart failure presents a significant medical problem and accumulating
      evidence indicates that slow relaxation during diastole maybe at least in part be
      medlated by decreased expression of the gene coding for the Ca2+ ATPase of the
      sarcoplasmic reticulum (SR). In order to determine if increased expression of the
      SR Ca2+ ATPase gene leads to alterations in calcium transients and in contractile
      behavior we constructed transgenic mice overexpressing the SERCA2 gene. Measuring
      dP/dt(max) and dpPdt(min) with a 2 French Milar catheter we found a significant
      Increase in systolic contraction and diastolic relaxation in transgene positive
      versus transgene negative mice. In addition we constructed adenoviruses
      overexpressing the gene coding for the Ca2+ ATPase of the sarcoplasmic reticulum.
      Infacting cardiac myocytes with the adenovirus expressing this transgene led to
      an accelerated calcium transient. Determining cell shortening and relengthening
      with a edge detection method indicated that increased expression of the SERCA2
      transgene mediated by adenovirus Infection accelerated contractile parameters. In
      summary increased expression of the SERCA2 transgene leads to an enhancement of
      cardiac contrectile parameters under in vivo conditions in transgenic mice and in
      myocytes in cell culture using an adenovirus based approach to increase
      expression of the SERCAX gene.

PMID- 8739239
TI  - Expression and regulation of chloride channels in neonatal rat cardiomyocytes.
AB  - Using an 125I- efflux assay, we have studied the expression of various types of
      chloride channels in isolated neonatal rat cardiomyocytes. Three different
      classes of anion conductances were distinguished: (1) a Ca(2+)-sensitive Cl-
      conductance, triggered upon stimulation of the cells with endothelin-1 or Ca(2+)
      ionophore; (2) a cAMP/protein kinase A-operated Cl- conductance, activated by
      addition of forskolin. This anion channel could be identified as the Cystic
      Fibrosis Transmembrane conductance Regulator (CFTR-CI- channel) by Western
      blotting as well as by its enhanced activity in cultures pretreated with the
      tyrosine kinase inhibitor genistein; (3) a distinct class of cell volume
      regulated Cl- channels, potentiated in the presence of endothelin-1 or the
      phosphotyrosine phosphatase inhibitor pervanadate. The potential role of each
      class of Cl- channels in the generation and/or modulation of action potentials as
      well as in maintaining cell volume is discussed.

PMID- 8739240
TI  - Paracrine functions of the coronary vascular endothelium.
AB  - Coronary vascular endothelial cells control vascular tone by modulating the local
      concentration of circulating vasoactive substances (e.g. adenine nucleotides,
      biogenic amines and bradykinin) and by synthesising and releasing the vasoactive
      autacoids nitric oxide (NO) and prostacyclin (PGI2). The fluid shear stress
      exerted by the streaming blood is the physiologically most important stimulus for
      a continuous endothelial NO production, which counteracts neuro- and myogenic
      constriction. This shear stress-dependent NO release represents a highly
      effective local system for maintaining adequate blood flow to the myocardial
      tissue. At the transcriptional level endothelium-derived NO modulates the
      regulation of a number of genes (e.g. monocyte chemoattractant protein-1, P
      selectin and vascular cell adhesion molecule-1) most probably by direct and/or
      indirect interaction with transcription factors. In addition to NO and PGI2, the
      coronary vascular endothelium is also able to release a factor which causes
      hyperpolarisation of the underlying smooth muscle. This so-called endothelium
      derived hyperpolarising factor (EDHF) displays the characteristics of a
      cytochrome P450-derived arachidonic acid metabolite. However, since NO is able to
      attenuate production of this factor, EDHF may contribute to the regulation of
      vascular tone essentially in situations associated with an apparent dysfunction
      of the endothelium.

PMID- 8739242
TI  - Comparison of calcium-current in isolated atrial myocytes from failing and
      nonfailing human hearts.
AB  - To identify possible alterations of the L-type calcium currents (I(Ca),L) in
      cardiomyopathy, I(Ca),L were recorded in atrial myocytes dissociated from the
      nonfailing heart (NF) of patients undergoing corrective open-heart surgery and
      explanted failing heart (FH) of patients with dilated cardiomyopathy undergoing
      heart transplantation. The patch-clamp technique was applied in the single
      electrode whole-cell mode. The electrophysiological properties of I(Ca),L,
      including cell capacitance and current density, were similar in atrial myocytes
      from both groups of patients. Further to identify possible alterations of the
      myocardial beta-adrenergic pathway in cardiomyopathy, we examined the effects of
      isoproterenol, forskolin, 8-Br-cAMP and IBMX on I(Ca),L in both groups of atrial
      myocytes. Perfusion of isoproterenol (1 microM) significantly increased the peak
      I(Ca),L by 515 +/- 44% in 6 atrial myocytes from NF but increased only by 135 +/-
      25% in 27 atrial myocytes from FH. However, forskolin (1 microM) or 8-Br-cAMP
      (0.1 mM) increased the peak I(Ca),L to a similar extent in atrial myocytes from
      NF and FH. IBMX (20 microM) also induced a comparable increase in the peak
      I(Ca),L by 213 +/- 31% (n = 5) and 207 +/- 59% (n = 4) in atrial myocytes from NF
      and FH, respectively. The above findings suggest that in atrial myocytes obtained
      from FH the beta-adrenoceptor numbers might be decreased but no impairment of the
      signal transduction cascade occurred beyond the GTP binding proteins level.

PMID- 8739241
TI  - Mechanical effects of ET-1 in cardiomyocytes isolated from normal and heart
      failed rabbits.
AB  - Endothelin (ET-1) is found at elevated concentrations in the plasma of patients
      with heart failure and in animal models of cardiomyopathy. The peptide is a
      potent positive inotropic agent, the effects of which are mediated by increases
      in cytosolic Ca2+ in cardiomyocytes. The object of this study was to investigate
      at the cellular level, the actions of ET-1 on contractile function and on Ca2+
      currents in heart-failed ventricular myocardium. Male New Zealand White rabbits
      (8 wks) were treated with twice weekly injections of epirubicin (4 mg/kg/wk, n =
      7) or with saline (n = 7) for 6 wks, followed by a washout period of 2 wks.
      Ventricular cardiomyocytes were isolated from rabbit hearts using Langendorff
      perfusion with collagenase; contractile function was examined using a video
      microscopy method, and L-type Ca2+ currents were recorded using a whole-cell
      patch-clamp technique. ET-1 produced a concentration-dependent increase in
      contractile response (% increase from basal value) to a maximum at 1 nM ET-1 of
      69 +/- 11% (mean +/- S.D.) in control cardiomyocytes and 33 +/- 6% in heart
      failed cells. However, there was no significant change in the EC50 obtained with
      ET-1 for healthy (0.31 +/- 0.1 nM) and for failed cardiomyocytes (0.24 +/- 0.1
      nM). The effects of ET-1 on L-type Ca2+ channels were similar with a peak
      amplitude at 1 nM ET-1 of -3.26 +/- 0.8 nA in control cardiomyocytes and -3.32 +/
      0.9 nA in heart-failed cells. The attenuation of the contractile response to ET
      1 in heart-failed cells may reflect a desensitization of ET receptors as a
      consequence of elevated circulating levels of ET and was not reflected by
      alteration of transmembrane Ca2+ conductance. It is probable, therefore, that
      multiple signalling pathways are involved in the actions of ET on ventricular
      myocardium.

PMID- 8739243
TI  - G-proteins and adenylyl cyclase signalling in hypertension.
AB  - The present studies were undertaken to examine if adenylyl cyclase activity and
      the levels of G-proteins (Gs alpha and Gi alpha) are altered in cardiovascular
      tissues in hypertension. Adenylyl cyclase activity and its responsiveness to
      stimulatory and inhibitory hormones as well as the expression of G-proteins (Gs
      and Gi) were determined at protein and mRNA levels by using specific antibodies
      and cDNA probes in hearts and aorta from 12 week old spontaneously hypertensive
      rats (SHR) and their age-matched control Wistar Kyoto (WKY) rats. The stimulatory
      effects of guanine nucleotides, isoproterenol, glucagon etc. on adenylyl cyclase
      activity were decreased in SHR rats as compared to the WKY rats, whereas, the
      inhibitory hormones inhibited enzyme activity to a greater extent in SHR rats as
      compared to WKY rats. Furthermore, the levels of Gi alpha-2 and Gi alpha-3
      proteins and Gi alpha-2 and Gi alpha-3 mRNA as determined by immunoblotting and
      Northern blotting techniques respectively were higher in SHR as compared to WKY
      rats. However, the levels of Gs alpha were unaltered in SHR. To further
      investigate if these alterations are the cause or effect of hypertension, the
      SHRs at various ages of development of blood pressure (3-5 days, 2, 4 and 8
      weeks) and their age-matched WKY were used for G-protein expression and adenylyl
      cyclase activity. The increased expression of Gi alpha-2 and Gi alpha-3 protein
      and mRNA levels in hearts and aorta were observed as early as in 2-weeks old SHR
      as compared to WKY, when the blood pressure was still normal. However, the levels
      of Gs alpha in SHR were not different from WKY rats. In addition, the altered
      responsiveness of adenylyl cyclase to hormone stimulation and inhibition was also
      observed as early as in 2 week old SHR. These results suggest that the increased
      expression of Gi alpha-2 and Gi alpha-3 and decreased levels of cAMP precedes the
      development of blood pressure and may be one of the contributing factors in the
      pathogenesis of hypertension.

PMID- 8739244
TI  - Protein phosphorylation in isolated trabeculae from nonfailing and failing human
      hearts.
AB  - Disturbances in the cAMP production during beta-adrenergic stimulation and
      alterations of Ca2+ transport controlling proteins and their regulation in the
      sarcoplasmic reticulum might be involved in the pathogenesis of the failing human
      heart. Thus, we investigated the cAMP-mediated phosphorylation of phospholamban,
      troponin I and C-protein in electrically driven, intact isolated trabeculae
      carneae from nonfailing and failing (NYHA IV) human hearts in parallel to
      contractile properties on the same tissue samples. The increase in force of
      contraction induced by isoproterenol (0.2 microM) or pimobendan (100 microM), a
      phosphodiesterase inhibitor, was diminished in the failing human hearts compared
      to nonfailing hearts by 49% and 36%, respectively. Concomitantly the
      isoproterenol-induced phosphorylation (pmol P/mg homogenate protein) of
      phospholamban, troponin I and C-protein was reduced from 13.0 +/- 2.4 (n = 4),
      30.5 +/- 1.5 (n = 5) and 11.0 +/- 1.3 (n = 5) in the nonfailing heart to 5.2 +/-
      0.6 (n = 13), 14.6 +/- 2.2 (n = 16) and 7.1 +/- 1.0 (n = 6) in the failing human
      heart, respectively. Pimobendan changed the phosphorylation state of these
      proteins similar to isoproterenol. The fact that combined addition of both agents
      or dibuturyl cAMP (1 mM) alone restored the phosphorylation capacity as observed
      in the control groups indicates that i) a reduced cAMP generation is related to
      the reduced phosphorylation of regulatory phosphoproteins located in the
      sarcoplasmic reticulum and contractile apparatus e.g. phospholamban, troponin I
      and C-protein, that ii) there is a relationship between protein phosphorylation
      state and contractile activity and that iii) no changes in the respective content
      of phosphoproteins are involved in the limitation of cAMP-mediated inotopic
      activity in the failing human heart.

PMID- 8739245
TI  - Regulation of expression of contractile proteins with cardiac hypertrophy and
      failure.
AB  - Transitions in sarcomeric alpha-actin and cardiac myosin heavy chain (MHC) gene
      expression have been useful as molecular markers for the development of cardiac
      hypertrophy and failure. In simpler model systems, alpha-actin expression has
      been useful in delineating some of the molecular pathways responsible for its
      induction following growth stimulation in vitro. In this study, we report that
      the effects of adrenergic agonists on alpha-actin expression in neonatal
      cardiocytes is dependent upon the culture conditions. In cardiocytes plated at 5
      x 10(4) cells/cm2, skeletal alpha-actin mRNA levels represent 47%, 37% or 42% of
      total sarcomeric alpha-actin accumulations following administrations of 4 microM
      norepinephrine (NE), isoproterenol (Iso), or phenylephrine (PE), respectively.
      Cultured cardiocytes treated with vehicle (ascorbate) only accumulated 19%
      skeletal alpha-actin. Under these tissue culture conditions, in contrast to data
      reported previously, skeletal alpha-actin expression is regulated by both alpha-
      and beta-adrenergic agonist stimulation. Furthermore, we present data showing
      that an endogenous anti-beta-MHC transcript is regulated by both pressure
      overload- or thyroxine-induced cardiac hypertrophy. Although anti-beta-MHC
      transcripts do not play a major role in regulating beta-MHC gene expression, the
      presence of this antisense transcript is associated with a novel set of beta-MHC
      degradation products. In vitro studies, where oligonucleotides complementary to
      beta-MHC have been introduced into cardiomyocytes, show that the mRNA levels of
      beta-MHC are decreased by 14-21% within 72 h after addition of the
      oligonucleotides. This result together with the presence of beta-MHC degradation
      products suggest that endogenous anti-beta-MHC transcripts may be involved in a
      post-transcriptional regulatory mechanism affecting the steady-state levels of
      beta-MHC expression.

PMID- 8739246
TI  - Beta-adrenoceptor mediated signal transduction in congestive heart failure in
      cardiomyopathic (UM-X7.1) hamsters.
AB  - In view of the lack of information regarding the status of beta-adrenoceptor
      mediated signal transduction mechanisms at severe stages of congestive heart
      failure, the status of beta-adrenoceptors, G-proteins and adenylyl cyclase
      activities was examined in 220-275 day old cardiomyopathic hamster hearts.
      Although no changes in the Kd values for beta 1- and beta 2-adrenoceptors were
      seen, the number of beta 1-adrenoceptors, unlike that of beta 2-adrenoceptors,
      was markedly decreased in cardiac membranes from failing hearts. The activation
      of adenylyl cyclase in the failing hearts by different concentrations of
      isoproterenol was also attenuated in comparison to the control preparations. The
      basal adenylyl cyclase activity in cardiac membranes from the failing hearts was
      not altered; however, the stimulated enzyme activities, when measured in the
      presence of forskolin, NaF or Gpp(NH)p were depressed significantly. The
      functional activity of Gs-proteins (measured by cholera toxin stimulation of
      adenylyl cyclase) was depressed whereas that of Gi-proteins (measured by
      pertussis toxin stimulation of adenylyl cyclase) was increased in the failing
      hearts. Not only were the Gs- and Gi-protein contents (measured by
      immunoblotting) increased, the bioactivities of these proteins as determined by
      ADP-ribosylations in the presence of cholera toxin and pertussis toxin,
      respectively, were also higher in failing hearts in comparison to the control
      values. Northern blot analysis revealed that the signals for Gs- and Gi-protein
      mRNAs were augmented at this stage of heart failure. These results indicate that
      the loss of adrenergic support at severe stages of congestive heart failure in
      cardiomyopathic hamsters may involve a reduction in the number of beta 1
      adrenoceptors, and an increase in Gi-protein contents as well as bioactivities in
      addition to an uncoupling of Gs-proteins from the catalytic site of adenylyl
      cyclase in cardiac membrane.

PMID- 8739248
TI  - Local renin-angiotensin systems.
AB  - The existence of a local cardiovascular renin-angiotensin system (RAS) is often
      invoked to explain the long-term beneficial effects of RAS inhibitors in heart
      failure and hypertension. The implicit assumption is that all components of the
      RAS are synthesized in situ, so that local angiotensin II formation may occur
      independently of the circulating RAS. Evidence for this assumption however is
      lacking. The angiotensin release from isolated perfused rat hearts or hindlimbs
      depends on the presence of renal renin. When calculating the in vivo angiotensin
      production at tissue sites in humans and pigs, taking into account the extensive
      regional angiotensin clearance by infusing radiolabeled angiotensin I or II, it
      was found that angiotensin production correlated closely with plasma renin
      activity. Moreover, in pigs the cardiac tissue levels of renin and angiotensin
      were directly correlated with their respective plasma levels, and both in tissue
      and plasma the levels were undetectably low after nephrectomy. Similarly, rat
      vascular renin and angiotensin decrease to low or undetectable levels within 48 h
      after nephrectomy. Aortic renin has a longer half life than plasma renin,
      suggesting that renin may be bound by the vessel wall. In support of this
      assumption, both renin receptors and renin-binding proteins have been described.
      Like ACE, renin was enriched in a purified membrane fraction prepared from
      cardiac tissue. Binding of renin to cardiac vascular membranes may therefore be
      part of a mechanism by which renin is taken up from plasma. It appears that the
      concept of a local RAS needs to be reassessed. Local angiotensin formation in
      heart and vessel wall does occur, but depends, at least under normal
      circumstances, on the uptake of renal renin from the circulation. Tissues may
      regulate their local angiotensin concentrations by varying the number of renin
      receptors and/or renin-binding proteins, the ACE level, the amount of
      metabolizing enzymes and the angiotensin receptor density.

PMID- 8739247
TI  - Polyunsaturated fatty acids and signalling via phospholipase C-beta and A2 in
      myocardium.
AB  - Dietary n-6 and n-3 polyunsaturated fatty acids (PUFAs) have potent biological
      effects on the blood(cells), the vasculature and they myocardium. In the
      epidemiological studies in which the benefit from the regular ingestion of n-3
      PUFAs was reported, the responsible mechanisms remain obscure. A great deal of
      the PUFA-effect can be explained by the known interference with the eicosanoid
      metabolism. Many processes, believed to be involved in atherogenesis such as
      adhesion and infiltration of bloodcells (in)to the vasculature, platelet
      aggregation, secretion of endothelium-derived factors and mitogenic responses of
      vascular smooth muscle cells are partially mediated by receptor-activated
      phospholipases C-beta and A2. As PUFAs take part at many steps of the signalling
      pathways, the latter could represent important action sites to beneficially
      interfere with atherogenesis. In this brief review, we have discussed the results
      of studies on the influence of alteration of PUFA composition of the membrane
      phospholipids or of exogenously administered non-esterified PURAs on phospholipid
      signalling. For convenience, we have mainly focused our discussion on those
      studies available on the myocardium. By changing the PUFA composition of the
      phospholipids, the endogenous substrates for the membrane-associated
      phospholipase C-beta and A2 are changed. This is accompanied by changes in their
      hydrolytic action on these substrates resulting in altered products (the
      molecular species of 1,2-diacylglycerols and the non-esterified PUFAs) which on
      their turn evoke changes in events downstream of the signalling cascades:
      activation of distinct protein kinase C isoenzymes, formation of distinct
      eicosanoids and non-esterified PUFA effects on Ca2+ channels. It has also become
      more clear that the membrane physicochemical properties, in terms of fluidity and
      cholesterol content of the bilayer, might undergo changes due to altered PUFA
      incorporation into the membrane phospholipids. The latter effects could have
      consequences for the receptor functioning, receptor-GTP-binding protein coupling,
      GTP-binding protein-phospholipase C-beta or A2 coupling as well. It should be
      noted that most of these studies have been carried out with cardiomyocytes
      isolated from hearts of animals on PUFA diet or incubation of cultured
      cardiomyocytes with non-esterified PUFAs in the presence of albumin. Studies need
      to be performed to prove that the PUFA-diet induced modulations of the
      phospholipid signalling reactions do occur in vivo and that these effects are
      involved in the mechanism of beneficial effects of dietary PUFAs on the process
      of atherosclerosis.

PMID- 8739249
TI  - Metabolism of linoleic and alpha-linolenic acids in cultured cardiomyocytes:
      effect of different N-6 and N-3 fatty acid supplementation.
AB  - The metabolites of linoleic (LA) and alpha-linolenic (ALA) acids are involved in
      coronary heart disease. Both n-6 and n-3 essential fatty acids (EFAs) are likely
      to be important in prevention of atherosclerosis since the common risk factors
      are associated with their reduced 6-desaturation. We previously demonstrated the
      ability of heart tissue to desaturate LA. In this study we examined the ability
      of cultured cardiomyocytes to metabolize both LA and ALA in vivo, in the absence
      and in the presence of gamma linolenic acid (GLA), eicosapentaenoic acid (EPA),
      docosahexaenoic acid (DHA) alone or combined together. In control conditions,
      about 25% or LA and about 90% of ALA were converted in PUFAs. GLA supplementation
      had no influence on LA conversion to more unsaturated fatty acids, while the
      addition of n-3 fatty acids, alone or combined together, significantly decreased
      the formation of interconversion products from LA. Using the combination of n-6
      and n-3 PUFAs, GLA seemed to counterbalance partially the inhibitory effect of
      EPA and DHA on LA desaturation/elongation. The conversion of ALA to more
      unsaturated metabolites was greatly affected by GLA supplementation. Each
      supplemented fatty acid was incorporated to a significant extent into
      cardiomyocyte lipids, as revealed by gas chromatographic analysis. The n-6/n-3
      fatty acid ratio was greatly influenced by the different supplementations; the
      ratio in GLA+EPA+DHA supplemented cardiomyocytes was the most similar to that
      recorded in control cardiomyocytes. Since important risk factors for coronary
      disease may be associated with reduced 6-desaturation of the parent EFAs,
      administration of n-6 or n-3 EFA metabolites alone could cause undesirable
      effects. Since they appear to have different and synergistic roles, only combined
      treatment with both n-6 and n-3 metabolites is likely to achieve optimum results.

PMID- 8739250
TI  - Alpha-tocopherol pretreatment improves endothelium-dependent vasodilation in
      aortic strips of young and aging rats exposed to oxidative stress.
AB  - Acetylcholine-induced, endothelium-dependent relaxation of norepinephrine
      precontracted aortic strips, was severely impaired after exposure to a
      hypoxanthine/xanthine oxidase reaction generating oxygen radicals. This effect
      was more evident in aortic strips of aging rats (24 months old) in comparison to
      young rats (3 months old). The addition of authentic .NO (1 microM) completely
      relaxed aortic strips exposed to oxidative stress both in young and aging rats.
      In vitro EPR measurements showed that the .NO signal was reduced by enzymatic O2.
      generating reaction. The activity of a partial purified preparation of
      constitutive NO synthase from rat cerebellum was significantly decreased after
      exposure to exogenous oxygen radicals. Pretreatment of aortic strips with 100
      microM alpha-tocopherol-phosphate, produced a significant improvement of
      acetylcholine-dependent relaxation in the aortic strips exposed to oxidative
      stress, particularly in the aged vessel. The content of malondialdehyde in aortic
      tissue did not change after oxidative stress or alpha-tocopherol pretreatment.
      Alpha-tocopherol was unable to recover the NO synthase activity depressed in
      vitro by hypoxanthine/xanthine oxidase reaction. This study confirms that an
      oxidative stress impairs the endothelium-mediated vasodilation. Alpha-tocopherol
      pretreatment protects the vessel against this damage. The mechanism of action of
      alpha-tocopherol is unknown, but seems unrelated to an antioxidant activity.

PMID- 8739251
TI  - Inositolpolyphosphates and their binding proteins--a short review.
AB  - Since 1983, when it was discovered that inositol 1,4,5-trisphosphate can act as
      second messenger to release Ca2+ from the endoplasmic reticulum, widespread
      research has focused on the phosphatidylinositol signalling transduction pathway
      and the host of inositolphosphates formed intracellularly after stimulation
      therof. Although the polyphosphates, inositoltetrakisphosphate (InsP4) and
      inositolhexakisphosphate (InsP6), have received their share of attention, a
      definite physiological role has not been ascribed to them as yet. Different
      binding proteins for these two polyphosphates have been demonstrated, especially
      in brain tissue, indicating their possible importance in the cell. InsP6 is known
      as one of nature's most powerful antioxidants and has already been demonstrated
      to possess the abilities to be of use in the industry as well as in the medical
      profession. As its natural actions are poorly understood and its possible side
      effects have not been widely investigated, basic research regarding its cellular
      and subcellular activities is urgently called for.

PMID- 8739252
TI  - Prevention of late lumen loss after coronary angioplasty by photodynamic therapy:
      role of activated neutrophils.
AB  - Restenosis after coronary angioplasty arises from fibrocellular intimal
      hyperplasia and possibly failure of the artery to enlarge adequately. Which
      mechanisms underlie this process is only partly understood. No drugs have been
      clinically effective in reducing the incidence of restenosis. Since recently,
      photodynamic therapy (PDT) is being investigated as a possible treatment for
      intimal hyperplasia. PDT involves the systemic administration of a light
      excitable photosensitizer that is taken up rather preferentially by rapidly
      proliferating cells. During laser irradiation light energy is transferred from
      the photosensitizer to oxygen generating the highly reactive singlet oxygen. This
      potent oxidizer can cause severe cellular damage. After PDT of a balloon-injured
      artery from the rat and rabbit the media remained acellular for several weeks to
      months, and intimal hyperplasia did not occur. The endothelial lining regenerated
      by two weeks, but why smooth muscle cells did not repopulated the media is not
      known. Neutrophils seem to play an important role in the prevention of restenosis
      after coronary angioplasty, since the activation status of this type of phagocyte
      is directly related to vessel diameter at late follow-up. Furthermore, it has
      been observed that neutrophils adhere to the microvascular wall upon PDT in vivo.
      In vitro findings suggest that the increased neutrophil adherence was not
      dependent on a decreased release of the anti-adhesive factors NO and prostacyclin
      by the PDT-treated endothelial cells. Furthermore, PDT did not stimulate the
      expression of P-selectin by the endothelial cells, one of the adhesion receptors
      for neutrophils. The endothelial cells only retract upon PDT allowing the
      adherence of neutrophils by their beta 2-integrin adhesion receptors to the
      subendothelial matrix. On the basis of these findings, we presume that the
      successful prevention of intimal hyperplasia by PDT partly depends on the
      presence of the neutrophil at the site of the lesion.

PMID- 8739253
TI  - Alpha-adrenergic reactivity of the microcirculation in conscious spontaneously
      hypertensive rats.
AB  - The goal of this study was to determine the functional distribution of alpha 1-
      and alpha 2-adrenoceptors in the striated muscle microcirculation. Experiments
      were performed in intact conscious spontaneously hypertensive rats (SHR) that
      were provided with a dorsal microcirculatory chamber to allow microvascular
      diameter measurements. Administration of selective alpha 1- and alpha 2-agonists,
      phenylephrine and azepexole, respectively, induced different patterns of
      microvascular constriction. alpha 1-Adrenoceptor stimulation showed a
      preferential constriction of large arteries and venules. The entire arteriolar
      microvasculature was sensitive to alpha 2-adrenoceptor stimulation, whereas the
      venular vessels did not respond to azepexole. The selective alpha 1- and alpha 2
      antagonists prazosin and yohimbine showed patterns of vasodilator activity
      comparable to those of the corresponding agonists. The specificity of the drug
      induced effects was verified by comparing their effects with those of graded
      hemorrhage, a non-pharmacological method for blood pressure lowering. In the
      range of blood pressure decreases comparable to that obtained by alpha
      adrenoceptor antagonists, graded hemorrhage did not influence microvascular
      diameters. These results show a differential functional distribution of alpha 1-
      and alpha 2-adrenoceptors along the microvascular tree in striated muscle of
      conscious SHR.

PMID- 8739254
TI  - Phosphodiesterase inhibition and Ca2+ sensitization.
AB  - Inhibitors of phosphodiesterase type III (PDE III) enhance cardiac contractile
      force by elevating the intracellular calcium concentration [Ca2+]i by impairing
      cAMP degradation thus increasing cAMP levels. The drugs are more effective in
      healthy than in failing hearts since basal cAMP production is diminished in the
      latter. However, long term treatment with PDE-III inhibitors does not appear to
      be beneficial due to increased risk of potentially lethal arrhythmias caused by
      augmentation of [Ca2+]i[1). This risk should be absent in Ca2+ sensitizers.
      Recently, thiadiazinone derivatives have been synthetized in which the potency
      for Ca2+ sensitization is many-fold larger than the potency for PDE-III
      inhibition. The Ca(2+)-sensitizing action resides in the [+]-enantiomers, while
      the [-]-enantiomers show weak PDE-III inhibition. In the enantiomer pair [+]-EMD
      60263 and [-]-EMD 60264, only the former concentration-dependently increased
      force of contraction in isolated cardiac preparations and myocytes. In the
      Langendorff-perfused guinea-pig heart, force was reversibly increased, whereas [
      ]-EMD 60264 even produced a negative inotropic response despite of its PDE
      inhibitory activity. Heart rate, however, was reduced by both enantiomers.
      Perfusion pressure remained unaffected. The effects were fully reversible upon
      wash-out of the enantiomers. [+]-EMD 60263 also enhanced cell shortening of human
      myocytes from both normal and failing hearts. In contrast to the opposite effects
      on contractility, both enantiomers prolong the action potential duration by
      blocking the rapidly activating component of the delayed rectifier K+ current.
      Thus they also possess class III antiarrhythmic activity. The therapeutic
      potential of these agents has yet to be assessed in clinical studies.

PMID- 8739255
TI  - Adrenergic and muscarinic receptor regulation and therapeutic implications in
      heart failure.
AB  - In end-stage heart failure the expression of different myocardial regulatory
      proteins involved in the beta-adrenergic cAMP signalling pathway is altered. The
      downregulation of beta 1-adrenoceptors and their uncoupling from the effector as
      well as an increased expression of the inhibitory GTP-binding protein seem to be
      the most important alterations. Since catecholamine levels are elevated in these
      patients and since some alterations can be 'restored' after treatment with beta
      adrenoceptor antagonists it was hypothesized that excessive beta-adrenergic
      stimulation could be involved in these alterations. In this article the changes
      of beta-adrenergic receptors, GTP-binding proteins, sarcoplasmic reticulum Ca(2+)
      ATPase and of phospholamban found in heart failure are addressed with its
      possible therapeutic implications.

PMID- 8739256
TI  - Endothelin and endothelin antagonists: potential role in cardiovascular and renal
      disease.
AB  - Endothelin-1 is a recently discovered peptide mainly released from endothelial
      cells. Hypoxia and ischemia as well as numerous factors such as angiotensin 11,
      thrombin and transforming growth factor beta 1 stimulate the formation of the
      peptide. On the other hand the synthesis of endothelin is inhibited by nitric
      oxide and atrial natriuretic peptide via the formation of cyclic guanosine
      monophosphate. Released from endothelial cells endothelin-1 mediates transient
      vasodilation followed by a profound and longlasting vasoconstriction. Endothelin
      is also a mitogen for smooth muscle proliferation. Endothelins exert their
      biological effects via activation of specific receptors. Two different receptors
      have been cloned from mammalian tissues (ET(A) and ET(B) receptors). On vascular
      smooth muscle cells both receptors mediate contractions. Endothelial cells only
      express ET(B) receptors linked to the formation of nitric oxide and/or
      prostacyclin formation. Increased plasma concentrations of endothelin-1 have been
      described in a variety of diseases such as pulmonary hypertension,
      arteriosclerosis, renal failure, acute coronary syndromes, heart failure,
      migraine and vascular diseases. Recently an increasing number of endothelin
      receptor antagonists have been synthetized, which have been shown to inhibit
      endothelin-mediated vasoconstriction. Clinical studies are now ongoing to
      elucidate the pathophysiologic role of endothelin and the potential benefit of
      the blockade of the system in different disease states.

PMID- 8739257
TI  - Helicobacter pylori infection and its role in human disease--an overview.
AB  - Helicobacter pylori (H. pylori) is probably the commonest chronic bacterial
      infection in humans. The bacterium colonizes the gastric epithelium and induces
      inflammation of the underlying mucosa. The recognition that this infection is the
      most important acquired factor in the pathogenesis of duodenal and gastric ulcers
      has transformed the management of these common disorders. Most patients with
      ulcers can be cured by a 1-week course of anti-H. pylori therapy, thereby
      removing the need for long-term acid inhibitory therapy. Eradication of the
      infection involves taking complex combinations of drugs and simpler eradication
      regimens are required. Recent epidemiological data indicate an association
      between H. pylori infection and the subsequent development of gastric carcinoma.
      If this association is established as causal, then widespread eradication of the
      infection may be indicated. Global eradication of H. pylori will probably rely on
      prophylactic or therapeutic vaccination and this approach is being actively
      investigated.

PMID- 8739258
TI  - The role of structure-based ligand design and molecular modelling in drug
      discovery.
AB  - Structure-based ligand design is a technique that is used in the initial stages
      of a drug development programme. The role of various computational methods in the
      characterization of the chemical properties and behaviour of molecular systems is
      discussed. The determination of the three-dimensional properties of small
      molecules and macromolecular receptor structures is a core activity in the
      efforts towards a better understanding of structure-activity relationships.

PMID- 8739259
TI  - Non-compliance in elderly people: evaluation of risk factors by longitudinal data
      analysis.
AB  - Studies on risk factors for drug non-compliance have not taken into account the
      possibility of correlated outcomes. We therefore conducted a study into risk
      factors for non-compliance by using analysis techniques that adjust for these
      correlations (longitudinal data analysis). Data were obtained from interviews and
      pharmacy records in a cross-sectional survey in Amsterdam. The subjects were 157
      elderly people aged 70 years or older. Of these subjects, 37 were residents of a
      home for the elderly, 40 were community-dwelling elderly who needed to be visited
      regularly by a district nurse, and 80 were community-dwelling elderly who did not
      need to be visited by a district nurse. Most drugs (78%) were used according to
      the directions; the remainder (22%) were not used as intended. Odds ratios (95%
      confidence intervals) for non-compliance for moderate and poor/wrong knowledge of
      the purpose of a drug as compared with good/correct knowledge were 2.8 (1.2-6.7)
      and 4.2 (1.5-12), respectively. Drug regimens of two times daily and more than
      two times daily were associated with odds ratios for non-compliance of 4.5 (1.6
      12) and 4.2 (1.7-11), respectively, compared to a regimen of once daily.
      Compliance increased if a drug was prescribed by a specialist instead of a
      general practitioner odds ratio 0.1 (0.04-0.4)]. There was no significant
      relation between compliance and the number of drugs prescribed to a patient, sex,
      age, living situation, patient group, or perceived effect. This study, which was
      based on longitudinal data analysis, demonstrates that in elderly people non
      compliance with drug therapy is related to the knowledge of purpose of a drug,
      the complexity of a drug regimen, and the type of prescriber. The positive
      association between compliance and the number of drugs prescribed found in former
      studies was not confirmed.

PMID- 8739260
TI  - Catha edulis, a plant that has amphetamine effects.
AB  - The chewing of fresh leaves of the khat bush (Catha edulis) is common in certain
      countries of East Africa and the Arab peninsula, because this material has a
      stimulating effect. During the last decade, important progress has been made in
      understanding the pharmacology of this drug. Its actions are mainly due to the
      alkaloid cathinone, a substance that can be called 'a natural amphetamine'.

PMID- 8739261
TI  - Stability of aztreonam in a portable pump reservoir used for home intravenous
      antibiotic treatment (HIVAT).
AB  - The stability of the monocyclic beta-lactam antibiotic aztreonam in portable pump
      reservoirs was studied during storage at temperatures of -20 degrees C and +5
      degrees C and during drug delivery at 37 degrees C. Three 100-ml drug reservoirs
      and three glass containers containing 60 mg/ml aztreonam were stored at -20
      degrees C and 2-ml samples were analysed in the freshly prepared solution and
      after thawing at days 7, 21, 28, 70 and after 6 months of storage. A separate
      triplicate batch of 100-ml prefilled drug reservoirs and glass containers
      containing a similar aztreonam concentration (60 mg/ml) were refrigerated and
      tested immediately after preparation and daily for 8 days and after 70 days.
      Solutions of aztreonam in duplicate freshly prepared reservoirs were tested for
      stability when the solution was pumped at 37 degrees C over a 24-h period. All
      solutions were inspected for visual changes and tested for pH. Drug concentration
      was analysed by high-performance liquid chromatography. No colour changes or pH
      differences were observed in any of the solutions in the reservoirs of
      containers. No statistically significant decrease in aztreonam concentration
      could be detected after 6 months of storage at -20 degrees C. Aztreonam was
      stable at 5 degrees C for at least 8 days. A 24-h pumping period at 37 degrees C
      showed a 3.6% decrease in aztreonam concentration. Aztreonam at a concentration
      of 60 mg/ml in a pump reservoir is sufficiently stable to be used in home
      intravenous antibiotic treatment programmes.

PMID- 8739262
TI  - Plasticizer extraction of Taxol infusion solution from various infusion devices.
AB  - Taxol solution extracts the plasticizer DEHP (di(2-ethylhexyl)phthalate) from
      polyvinyl chloride (PVC) materials. In order to minimize patient exposure to
      DEHP, Taxol solutions should be prepared and administered in PVC-free materials.
      Particulate matter may form in Taxol infusion solution over time, so that in-line
      filtration with microporous membranes not greater than 0.22 microns is advisable.
      The purpose of this study was to evaluate the suitability of various
      administration- and in-line filter-sets for Taxol application. The extent of
      leached DEHP was determined using a Reversed Phase HPLC assay specific for DEHP.
      The four tested administration-sets, labeled as PVC-free, were all found to be
      suitable for Taxol application. The tested standard PVC-lined administration-set
      should not be used for Taxol application. Baxter Intermate LV 250 can be
      recommended as a disposable infusion device for ambulatory Taxol application. It
      can be connected with all the tested filter sets.

PMID- 8739263
TI  - APOM-project: an investigation of pharmacy organization and management.

PMID- 8739264
TI  - Preparation and stability testing of a hydrogel for topical analgesia.

PMID- 8739265
TI  - Diffusion NMR.

PMID- 8739266
TI  - Interpretation of DW-NMR data: dependence on experimental conditions.
AB  - This review examines the effect of experimental conditions on the data obtainable
      from diffusion weighted NMR experiments. The origin and forms of the Stejskal
      Tanner experiment are presented, and the relative merits of bipolar to monopolar
      diffusion weighting gradient pulses are discussed, as are those of spin-echo and
      stimulated-echo weighting schemes. The short pulse Stejskal-Tanner experiment as
      required for q-space imaging is described. Criteria for successful diffusion
      weighted imaging are given, and current strategies for diffusion weighted imaging
      are evaluated against these. The range of biological objects accessible to
      diffusion weighted NMR is summarized, together with the associated experimental
      limitations. In the final section the dependence of diffusion weighted NMR data
      on diffusion time and b-value range is examined, and the relationship between
      apparent restricted diffusion and the size of the extracellular space is
      demonstrated.

PMID- 8739267
TI  - Diffusion-weighted imaging in tissues: theoretical models.
AB  - Typical diffusion measurements use Stejskal-Tanner pulsed gradient spin echo
      sequences to provide information about the average diffusion and displacement
      profiles of particles in a sample. To derive structural information, a measured
      displacement profile has to be related by means of a model to the physical and
      geometrical properties of the tissue, such as diffusion coefficients and shapes
      of semi-permeable membranes of compartments in the system. The behavior of the
      NMR signal and the measured ADC are greatly affected by the cellular architecture
      of a tissue, mainly because cellular membranes are relatively impermeable to
      water. For long diffusion times, and small signal attenuations, ADC is relatively
      insensitive to how it is measured. In general, however, ADC values are not
      readily interpreted unless the measuring conditions are specified in detail. For
      given measuring conditions, ADC depends on intra- and extracellular diffusion
      coefficients, membrane permeabilities, cell sizes and the cellular volume
      fraction. If intra- and extracellular T2 relaxation rates are different enough,
      ADC may also depend on the relaxation properties of the system and the echo time.
      An improved understanding of the precise influence of these factors has been
      obtained by detailed consideration of theoretical and computer models that can be
      related to experimental data in simple systems. Further refinements of such
      models should advance our understanding of water diffusion in tissues.

PMID- 8739268
TI  - The application of porous-media theory to the investigation of time-dependent
      diffusion in in vivo systems.
AB  - Recent developments in solid-boundary porous-media theory have shown that useful
      structural information can be extracted from the time-dependent diffusion
      coefficient, D(t), of the fluid filling the interstitial space. This theoretical
      framework provides a basis from which to understand the results from diffusion
      experiments performed in other types of systems (e.g. biological). Structural
      information about porous media can be obtained from the short-time behavior of
      D(t) in the form of the ratio of the surface area to pore volume, S/V. The long
      time behavior of D(t) in porous media provides an indirect measure of the
      macroscopic structure. In this case, the long-time diffusion coefficient, D(eff),
      reflects the tortuosity, T, of the medium; a property of both the connectivity of
      the diffusion paths and the volume fraction of the sample. Measurements of D(t)
      were performed in RIF-1 tumors, using both spectroscopy and imaging, and the data
      were used to calculate S/V and T. The results were compared with histological
      sections in order to correlate S/V and T with differences in tissue structure
      (i.e. necrotic vs non-necrotic tumor tissue). Based on spectroscopic
      measurements, there is a trend towards decreasing S/V and T with increasing tumor
      volume, consistent with the interpretation that water in necrotic tissue is
      experiencing relatively fewer restricting barriers (as compared to non-necrotic
      tumor tissue). Based on D(t) maps generated from RIF-1 tumors, D(eff), and hence
      T appears to be much more sensitive than S/V in differentiating between necrotic
      and non-necrotic tissue. In addition to characterizing diseased tissue, S/V and
      particularly T appear to be sensitive to structural changes that would accompany
      tumor treatment and should therefore provide a useful tool for monitoring the
      progress of therapeutic interventions.

PMID- 8739269
TI  - Diffusion MRI: precision, accuracy and flow effects.
AB  - After a decade of evolution and application of diffusion imaging, a large body of
      literature has been accumulated. It is in this context that the accuracy and
      precision of diffusion-weighted and quantitative diffusion MRI are reviewed. The
      emphasis of the review is on practical methods for clinical human imaging,
      particularly in the brain. The requirements for accuracy and precision are
      reviewed for various clinical and basic science applications. The methods of
      measuring and calculating diffusion effects with MRI are reviewed. The pulse
      gradient spin echo (PGSE) methods are emphasized as these methods are used most
      commonly in the clinical setting. Processing of PGSE data is reviewed. Various
      PGSE encoding schemes are also reviewed in terms of the accuracy and precision of
      isotropic and anisotropic diffusion measurements. The broad range of factors
      impacting the accuracy of the PGSE methods and other encoding schemes is then
      considered. Firstly, system inaccuracies such as background imaging gradients,
      gradient linearity, refocusing RF pulses, eddy currents, image misregistration,
      noise and dynamic range are considered. A second class of inaccuracies is
      contributed by the bulk effects of the imaged object, and include sample
      background gradients, subject motion of cerebrospinal fluid and organs, and
      aperiodic organ motion. A final category of potential inaccuracies is classified
      as being contributed by microscopic, biophysical tissue properties and include
      partial volume effects, anisotropy, restriction, diffusion distance,
      compartmentation, exchange, multiexponential diffusion decay, T2 weighting and
      microvascular perfusion. Finally, the application of diffusion methods to studies
      of blood flow in the microvasculature (i.e. the arterioles, capillaries and
      venules) are reviewed in detail, particularly in terms of feasibility and the
      stringent accuracy and precision requirements. Recent provocative studies
      examining the use of PGSE approaches to suppress microvascular signals in brain
      functional MRI (fMRI) are also reviewed.

PMID- 8739270
TI  - Inferring microstructural features and the physiological state of tissues from
      diffusion-weighted images.
AB  - We review several methods that have been developed to infer microstructural and
      physiological information about isotropic and anisotropic tissues from diffusion
      weighted images (DWIs). These include Diffusion Imaging (DI), Diffusion Tensor
      Imaging (DTI), isotropically weighted imaging, and q-space imaging. Just as DI
      provides useful information about molecular displacements in one dimension with
      which to characterize diffusion in isotropic tissues, DTI provides information
      about molecular displacements in three dimensions needed to characterize
      diffusion is anisotropic tissues. DTI also furnishes scalar parameters that
      behave like quantitative histological or physiological 'stains' for different
      features of diffusion. These include Trace(D), which is related to the mean
      diffusivity, and a family of parameters derived from the diffusion tensor, D,
      which characterize different features of anisotropic diffusion. Simple thought
      experiments and geometrical constructs, such as the diffusion ellipsoid, can be
      used to understand water diffusion in isotropic and anisotropic media, and the
      NMR experiments used to characterize it.

PMID- 8739271
TI  - Diffusion-weighted NMR imaging: application to experimental focal cerebral
      ischemia.
AB  - Changes in diffusion NMR imaging are believed to be based on intra/extracellular
      water homeostasis and will therefore reflect early disturbances of ion and water
      homeostasis after the onset of an ischemic event. Diffusion-weighted NMR imaging
      (DWI) thus has the potential to be a sensitive tool for the observation of stroke
      evolution. The present state of information extracted from diffusion-weighted NMR
      imaging for the understanding of cerebral focal ischemia in experimental research
      has been compiled in this review. The emphasis was set on three essential aspects
      of the technique in relation to focal ischemia. Firstly, the sensitivity of
      diffusion-weighted imaging for ischemic alterations is described. A comparison
      with conventional NMR imaging using relaxation time changes is included.
      Secondly, the comparison of the diffusion-weighted imaging with invasive
      techniques is discussed. Here, interpretation of the physiological, metabolic and
      hemodynamic alterations reflected in the observed diffusion changes is presented.
      The importance of regionally resolved information for a meaningful assignment of
      DWI changes to pathophysiological alterations is demonstrated for the
      differentiation between ischemic core and penumbra from DWI and quantitative
      diffusion coefficient data. The time dependence of correlations with
      physiological, biochemical and hemodynamic variables as a further important
      aspect is stressed. Thirdly, the potential of the technique for the assessment of
      development and effectiveness of new therapeutical strategies against stroke is
      demonstrated.

PMID- 8739272
TI  - Diffusion-weighted NMR imaging changes caused by electrical activation of the
      brain.
AB  - The apparent diffusion coefficient of brain water was decreased by frontal
      cortical electroshock, usually but not always associated with brief epileptic
      afterdischarge detectable at the parietal cortex. Previous studies have shown
      that status epilepticus causes similar larger decreases, which are largely
      reversible by the termination of seizure discharge with pentobarbital. Cerebral
      blood flow is elevated in these conditions, and biochemical energy failure does
      not occur. The brain water diffusion coefficient also decreases in spreading
      depression, without depletion of energy stores. All of these findings may be due
      in part to the reduction of brain extracellular space caused by cell swelling,
      which occurs to some degree in all three conditions. However, major biological
      differences between brain activation and brain ischemia and new evidence for
      increased cytosolic viscosity in the latter both suggest that other mechanisms
      deserve further investigation. Use-dependent motility of dendritic spines and
      other phenomena that may allow direct detection of neural activity by diffusion
      weighted NMR imaging are of special interest.

PMID- 8739273
TI  - In vivo diffusion spectroscopy. An overview.
AB  - This review describes in vivo NMR measurements of metabolite diffusion. NMR
      spectroscopy can employ a variety of endogenous marker molecules to obtain
      information on various aspects of in vivo biochemistry and biophysics from the
      diffusion characteristics of these markers. NMR-based metabolite diffusion data
      give an insight into the physico-chemical properties of the intracellular
      compartment and of changes therein in relation to development and pathology.
      Recent applications have proven that in vivo diffusion spectroscopy provides
      exciting opportunities to both fundamental and applied research.

PMID- 8739274
TI  - Molecular diffusion, tissue microdynamics and microstructure.
AB  - Diffusion NMR is the only method available today that noninvasively provides
      information on molecular displacements over distances comparable to cell
      dimensions. This information can be used to infer tissue microstructure and
      microdynamics. However, data may be fairly difficult to interpret in biological
      tissues which differ markedly from the theoretical "infinite isotrope medium", as
      many factors may affect the NMR signal. The object of this paper is to analyze
      the expected effects of temperature, restriction, hindrance, membrane
      permeability, anisotropy and tissue inhomogeneity on the diffusion measurements.
      Powerful methods, such as q-space imaging, diffusion tensor imaging and diffusion
      spectroscopy of metabolites further enhance the specificity of the information
      obtained from diffusion NMR experiments.

PMID- 8739275
TI  - Clinical aspects of DWI.
AB  - Diffusion-weighted MR imaging (DWI) is capable of imaging ischemia-induced
      changes in water protons in either animal or man. Technical developments are
      described that allow the routine clinical utility of DWI in a stroke setting to
      provide objective criteria beyond the neurological exam by which the
      pathophysiology of stroke can be evaluated. To date, DWI has provided unique
      information concerning detection and evaluation of acute, symptomatic lesions
      from older, chronic strokes, detection and localization of small deep infarcts
      and reversible ischemic neurologic deficits and transient ischemia. Clinical DWI
      studies suggest that the temporal behaviour of ADC can critically improve the
      evaluation of clinical ischemia.

PMID- 8739276
TI  - Cardiovascular effects of increasing hemoglobin in chronic renal failure.
AB  - Partial correction of renal anemia by the use of recombinant human erythropoietin
      is associated with various effects on cardiovascular performance parameters. A
      decrease in cardiac output as well as an increase in systemic peripheral
      resistance have been noted and the pathogenetic basis of these changes will be
      discussed. Furthermore this article will focus on the potential cardiovascular
      consequences of prolonged correction of anemia in patients with renal failure.
      The literature on the clinical implications, such as left ventricular
      hypertrophy, peripheral arterial occlusive disease and finally patient care
      costs, will be discussed.

PMID- 8739277
TI  - Effectiveness of intravenous administration of Fe-gluconate-Na complex to
      maintain adequate body iron stores in hemodialysis patients.
AB  - The evolution of body iron stores was prospectively analyzed during a stable
      erythropoiesis period in 27 subjects (14 males and 13 females) on hemodialysis
      for more than 2 years in order to clarify the iron requirements of these patients
      and the effectiveness and safety of the administration of sodium ferric gluconate
      as a method to maintain adequate body iron stores. All patients had a stable
      hemoglobin level (variation < 1 g/dl). Sixteen subjects were on maintenance
      recombinant human erythropoietin therapy at regular doses. All patients received
      intravenous sodium ferric gluconate for 6 months (62.5 mg/month). The iron
      requirements were estimated as the difference between the amount of iron
      administered and the variation of body iron stores (calculated by the empirical
      formula of Cook and coworkers). The hemoglobin remained stable (basal 10.7 +/-
      1.1, at 6th month 10.6 +/- 1 g/dl). Considering all cases, there were no
      significant variations in body iron stores (basal 457 +/- 273, at 6th month 451
      +/- 316 mg). The patients were classified into three groups according to whether
      their body iron stores decreased (group A, n = 8), remained stable (group B, n =
      11), or increased (group C, n = 8). There were no differences among groups
      concerning sex, age, time on hemodialysis, or erythropoietin therapy. However,
      there were statistically significant differences concerning their basal body iron
      stores (group A 457 +/- 228 mg. group B 563 +/- 146, and group C 230 +/- 297 mg;
      p < 0.05, analysis of variance). The iron needs, considering the total group,
      were 2.12 +/- 2 mg/day. There were no differences in iron requirements according
      to sex, but menstruating women had higher iron needs than the nonmenstruating
      ones (4.29 +/- 2 vs. 2.08 +/- 1.45 mg/day; p < 0.01). The iron requirements in
      patients on erythropoietin therapy were higher than in those without (2.63 +/-
      1.59 vs. 1.88 +/- 1.68 mg/day; p < 0.05). However, excluding the menstruating
      women, the iron need in patients on erythropoietin were similar to those in
      subjects without this treatment (2.16 +/- 1.13 vs. 1.88 +/- 1.68 mg/day). All
      patients showed good compliance with an excellent tolerance. We have observed
      that in subjects on maintenance erythropoietin therapy, the iron requirements are
      stable. The administration of sodium ferric gluconate is safe and efficient in
      maintaining adequate body iron stores.

PMID- 8739278
TI  - Increased serum neutral endopeptidase activity in acute renal allograft
      rejection.
AB  - Neutral endopeptidase (EC 3.4.24.11; NEP), originally isolated from renal tubular
      brush border, is a cell surface peptidase identical to the CD10 antigen (or
      CALLA; common acute lymphoblastic leukemia antigen) in lymphoid cells. We studied
      the serum NEP levels daily after transplantation (Tx) in 19 renal allograft
      recipients. The NEP activity was determined with a two-step enzymatic assay
      utilizing a fluorogenic substrate (Suc-Ala-Ala-Phe-AMC; see text) and related to
      clinical signs of graft rejection, to signs of immunoactivation in transplant
      fine-needle aspiration biopsy (FNAB) specimens, to renal function, and to serum
      levels of C-reactive protein. The serum NEP levels remained normal (peak level
      10.3 +/- 1.8 micrograms/l on days 6-9 after Tx, initial level after Tx 7.3 +/-
      1.4 micrograms/1 on day 2; mean values +/- SEM) in patients who neither showed
      clinical signs of rejection nor had findings of immunoactivation in FNAB samples.
      On the contrary, the serum NEP levels rose clearly in patients developing acute
      rejection verified clinically and in FNAB samples (peak value 90.4 +/- 18.7
      micrograms/l on days 6-9 post-Tx; p < 0.001 compared with patients without sings
      of immunoactivation) and even in patients having immunoactivation in FNAB without
      clinical evidence of rejection (108.2 +/- 22.4 micrograms/l, p < 0.001). Serum
      NEP peak appeared 2-3 days before clinical diagnosis of rejection and a positive
      findings in FNAB samples. Serum NEP increments did not correlate with changes in
      serum creatinine, delayed onset of renal excretory function, blood leukocyte
      count, C-reactive protein level, or infections. Thus, the serum NEP activity was
      shown to increase after renal allotransplantation associated with early phases of
      immunoactivation and development of acute graft rejection. Because of the limited
      number of patients studied, the clinical implications of these preliminary
      observations for kidney transplant monitoring clearly need confirmation in larger
      studies.

PMID- 8739279
TI  - Predictors of survival in HIV-infected patients on hemodialysis.
AB  - We undertook the present study to determine whether there might be variables
      other than CD4 counts which might help predict survival of HIV-infected patients
      who are placed on chronic hemodialysis, survival which often is extremely poor.
      We studied prospectively (n = 18) and retrospectively (n = 6) 24 consecutive HIV
      positive patients on chronic hemodialysis at our institution over a 7-year period
      and recorded clinical and laboratory variables at the time of initiation of
      dialysis. The mean survival for the group as a whole was 11 +/- 8 (range 2-32)
      months. A highly significant positive correlation was found between survival and
      CD4 counts (p < 0.001) and blood pressure (systolic, p < 0.02; diastolic, p <
      0.05; mean arterial, p < 0.05). Infection rate and urine protein excretion both
      had significant negative correlations with survival (p < 0.01 and p < 0.02,
      respectively). The presence of edema appeared to have a positive effect on
      survival (p < 0.01). The use of antiretroviral therapy resulted in significantly
      greater survival of HIV-infected patients (15.2 +/- 2.2 vs. 6.2 +/- 1.2 months, p
      < 0.01). Using a general linear model, it was found that CD4 count and systolic,
      diastolic, and mean arterial blood pressures and infection rate all were
      independent estimators of survival. We conclude that variables other than CD4
      counts might also be useful in predicting survival in HIV-infected patients on
      chronic hemodialysis.

PMID- 8739280
TI  - Apolipoprotein AI and apolipoprotein B containing particle analysis in
      normolipidemic hemodialyzed patients: evidence of free apolipoprotein E.
AB  - Whole plasma from 6 normolipidemic chronic renal failure (CRF) patients
      undergoing hemodialysis treatment was passed through the anti-apolipoprotein
      (Apo) AI immunosorbent column connected to the anti-Apo B immunoaffinity column.
      Apo AI and B containing particles were analyzed for lipid and Apo contents. The
      results were compared with findings obtained in age-matched normolipidemic
      healthy controls. Although plasma Apo AI and AII levels decreased in CRF
      patients, the concentrations of Apo CII, CIII, and E coeluted with Apo AI were
      similar to those of the controls. The slightly elevated plasma concentrations of
      Apo CII and CIII in the CRF patients studied were shown to be associated with Apo
      B containing particles. The nonretained fraction from both groups contains no Apo
      AI and no Apo B, but still contains lipids and other Apo such as Apo AII and Apo
      CII. The occurrence of approximately 29% of plasma Apo E in this fraction
      constitutes the main abnormality found in these patients (< 5% in controls). A
      two-phase electroimmunoassay shows that this Apo E did not correspond to the
      plasma E-AII complex. These findings show that the compositional alterations of
      Apo AI and Apo B containing particles in CRF patients were observed even in
      normolipidemic patients and suggest that the kidney may play a metabolic role in
      the removal of free forms of lipoprotein particles such as free Apo E.

PMID- 8739281
TI  - Cytokine production during hemodialysis: effects of dialytic membrane and
      complement activation.
AB  - Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are
      closely associated with acute and chronic inflammatory processes in hemodialytic
      patients. However, the mechanisms concerning cytokine production by monocytes
      during hemodialysis are still conflicting. With the use of the more specific
      monoclonal antibody ELISA method, contamination detection and crossover protocol
      of complement-activating and noncomplement-activating hollow fibers, we were able
      to confirm augmented II-1 beta production by zymosan-stimulated monocytes with
      complement-activating hollow fiber as compared to noncomplement-activating hollow
      fiber before (1,411.9 +/- 865.7 +/- 149.9 pg/ ml/2 x 10(6) monocytes, p < 0.01).
      at the 15th minute (530.6 +/- 89.1 vs. 247.3 +/- 45.2 pg/ml/2 x 10(6) monocytes,
      p < 0.01) and at the end of dialysis (1,201.8 +/- 135.1 vs. 707.4 +/- 109.3
      pg/ml/2 x 10(6) monocytes, p < 0.01). Similar results were observed with TNF
      alpha production. IL-1 beta as well as TNF-alpha production decreased
      significantly at the 15th min of dialysis, thereafter they increased and
      approached the baseline levels towards the end of hemodialysis with both hollow
      fibers. Plasma C3a at the 15th minute correlated positively with postdialysis IL
      1 beta and TNF-alpha production, while plasma C3a did not change in patients
      dialyzed with noncomplement-activating hollow fiber. Complement activation with
      complement-activating hollow fiber as well as monocyte-membrane interaction with
      complement-activating and noncomplement-activating hollow fiber might be involved
      in the pathogenesis of cytokine production during hemodialysis. Uremic toxin
      removal as well as stimulation of cytokine production inhibitor might contribute
      to the decreased cytokine production at the 15th minute of hemodialysis and
      monocyte-membrane interaction with or without complement activation resulted in
      augmented cytokine production toward the end of hemodialysis with both hollow
      fibers. We thus concluded that hollow fiber of bioincompatibility triggered much
      more cytokine production throughout the dialysis procedure.

PMID- 8739282
TI  - Urinary N-acetyl-beta-D-glucosaminidase activity in children with insulin
      dependent diabetes mellitus.
AB  - Urinary N-acetyl-beta-D-glucosaminidase (NAG) is a sensitive indicator of renal
      tubular injury. The aim of the study is to determine the status of urinary NAG
      excretion in Chinese children with insulin-dependent diabetes mellitus (IDDM) but
      without any clinical evidence of nephropathy, and to try to find the possible
      associated factors of such tubular injury if any. Thirty-one children (8 males
      and 23 females) with IDDM who have normal serum creatinine, 24-hour urinary
      creatinine clearance and urinary total protein excretion were enrolled in the
      study. The mean age of the patients was 11.6 +/- 3.7 years. The random urinary
      NAG levels of the patients and the normal controls were 10.76 +/- 6.32 and 3.65
      +/- 1.84 U/g Cr, respectively (p < 0.001). The diabetic patients were divided
      into 4 groups according to their duration of disease ( < 3, 3-5, 5-10 and 10-16
      years). The random urinary NAG level of each group was significantly higher than
      that of the control group, but there was no statistically significant difference
      among any 2 of these 4 groups. No good correlation was noted in our study between
      urinary NAG and patients' age (r = -0.23, p = 0.21), serum cholesterol (r = 0.04,
      p = 0.84), insulin dosage (r = 0.13, p = 0.49), 24 hour urinary creatinine
      clearance (r= -0.41, p - 0.085) or urinary total protein excretion (r = -0.28, p
      = 0.26). However, the plasma HbAlc level correlated significantly with urinary
      NAG (r = 0.50, p < 0.01). We concluded that urinary NAG is increased in Chinese
      IDDM children without any clinical evidence of nephropathy. Such increased
      excretion is correlated with the plasma HbAlc level. Our results suggests that
      there is tubular dysfunction in the early stage of IDDM children even before
      there is any clinical evidence of nephropathy, and urinary NAG may reflect
      glycemic control in such patients.

PMID- 8739283
TI  - Early and late effects of erythropoietin on glucose metabolism in maintenance
      hemodialysis patients.
AB  - The effects of recombinant human erythropoietin (rHuEPO) on the glucose
      metabolism were evaluated by intravenous glucose tolerance test in 20 maintenance
      hemodialysis patients. In 8 cases the glucose tolerance tests were performed
      before and after a single intravenous injection of 50 IU/kg of rHuEPO and in 12
      cases before and after 3 months of rHuEPO therapy at doses of 50 IU/kg three
      times/week and 2 weeks after rHuEPO withdrawal. For each test glucose,
      immunoreactive insulin (IRI) and C peptide (C-p) plasma values were measured, and
      glucose constant decay, whole IRI (area IRI) and C-p area C-p) production,
      insulinogenic index, and insulin resistance index were calculated. After 3 months
      of rHuEPO therapy, the glucose constant decay increased significantly, area IRI,
      area C-p, and insulin resistance index decreased significantly, and the
      insulinogenic index did not change. No correlations were found between changes in
      hemoglobin values and changes in glucose metabolism parameters. Acute rHuEPO
      administration and rHuEPO withdrawal had no effect on glucose metabolism, despite
      significant changes in plasma erythropoietin levels. Long-term rHuEPO therapy
      improves glucose metabolism in maintenance hemodialysis patients significantly,
      mainly by reduction of insulin resistance. Neither anemia correction nor a direct
      effect of rHuEPO on some metabolic steps seem to be responsible of these effects.

PMID- 8739284
TI  - Significance of serum lipase in patients undergoing hemodialysis.
AB  - Serum levels of lipase (Lp) during the end of the dialysis showed a significant
      increase after the administration of heparin in hemodialysis patients. However,
      serum Lp levels were not increased after the administration of the anti-coagulant
      nafamostat mesylate in hemodialysis patients. Serum levels of Lp were
      significantly correlated with serum levels of lipoprotein lipase (LPL), hepatic
      triglyceride lipase (H-TGL) and nonesterified fatty acid (NEFA) 20 min after the
      administration of heparin during maintenance hemodialysis. Lp activity did not
      appear with the NEFA ligand for determining the NEFA activity. Inhibitors of LPL
      and H-TGL reduced the measured Lp activity in vitro. The main mechanism of
      elevated measured serum Lp activity in hemodialysis patients was determined to be
      cross-reactivity with LPL or H-TGL. Furthermore, measurement of Lp may be a
      method for determining optimal coagulation time in patients with hemodialysis.

PMID- 8739286
TI  - Renal disease in Marfan syndrome.
AB  - We encountered 4 individuals with Marfan syndrome who presented with
      microhematuria and proteinuria. In 2 of them, a renal biopsy was performed. The
      predominant glomerular change by light microscopy was a focal segmental increase
      in mesangial matrix with early sclerotic lesions. Ultrastructurally, there was
      variable subendothelial widening containing haphazardly arranged microfibrils, 10
      13 nm in diameter. Changes in small arteries present in the biopsies were mild in
      case 1 and more striking in case 2 which consisted of elastolysis and
      fragmentation and focal disruption of internal elastic lamina, and focal
      degenerative changes in the media. In light of observations on the abnormalities
      of microfibrillar protein (fibrillin) in the microfibrillar-fiber system and the
      presence of abnormal type IV collagen in the connective tissues in Marfan
      syndrome, the glomerular basement membrane alterations may be related to these
      defects and lead to microhematuria and proteinuria.

PMID- 8739285
TI  - Enalapril attenuates the renal hemodynamic effect of acetazolamide in patients
      with diabetes mellitus: possible implications for tubuloglomerular feedback.
AB  - Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, causes a fall in renal
      plasma flow and glomerular filtration (GFR). It is generally believed that the
      tubuloglomerular feedback (TGF) mechanism is responsible. This study examined
      whether, in patients with diabetes mellitus, the renal hemodynamic response to
      ACTZ is intact and whether the angiotensin-converting enzyme inhibitor,
      enalapril, which would be expected to block TGF, attenuates this response to
      ACTZ. Six men with insulin-dependent diabetes mellitus lived in a clinical
      research center for 8 weeks and received enalapril 5-15 mg/day from the third
      through sixth week. At 2, 6 and 8 weeks p-aminohippurate (PAH) and inulin
      clearances were performed over eleven 30-min periods. ACTZ (150 mg) was given
      intravenously after 180 min. In both the pre- and postenalapril studies, PAH
      clearance fell after ACTZ administration (-60 +/- 15 and -66 +/- 20 ml/min/l1.73
      m2, respectively, p < 0.05 for each study). In contrast, with enalapril treatment
      PAH clearance after ACTZ tended to rise (29 +/- 12 ml/ min/1.73 m2, p = 0.07).
      GFR after ACTZ fell during the pre- and postenalapril studies (-19 +/- 3 and -13
      +/- 1 ml/min/1.73 m2, respectively, p < 0.05 for each study) but not with
      enalapril treatment (-6 +/- 3 ml/min/1.73 m2). After ACTZ was administered,
      estimated renal vascular resistance rose during both the pre- and postenalapril
      studies (p < 0.05 and p < 0.01, respectively) and fell with enalapril treatment
      (p < 0.05). These data indicate that enalapril alters the renal hemodynamic
      effects of ACTZ in patients with diabetes mellitus, possibly by inhibiting
      tubuloglomerular feedback.

PMID- 8739287
TI  - Diminished protein binding capacity of uremic sera for valproate following
      hemodialysis: role of free fatty acids and uremic compounds.
AB  - We previously reported higher free phenytoin concentration in predialysis serum
      compared to postdialysis serum. In our present study with valproic acid, we
      observed an opposite effect, where free valproic acid concentration was higher in
      postdialysis serum. The increased free valproic acid concentrations in
      postdialysis sera (15.4-77.4% higher in postdialysis sera) were probably related
      to a 2-to 4-fold increase in free fatty acid concentrations in postdialysis sera.
      On the other hand, when an aliquot of predialysis serum pool was subjected to in
      vitro equilibrium dialysis and then both undialyzed and dialyzed serum pools were
      supplemented with valproic acid and incubated, the concentration of valproic acid
      in dialyzed serum was significantly lower than the undialyzed serum. This is
      probably related to removal of some uremic compounds during in vitro dialysis.
      Treatment of both pre- and postdialysis sera with activated charcoal corrected
      the binding deficiency of valproic acid due to removal of both uremic compounds
      and free fatty acids.

PMID- 8739288
TI  - Renal failure in a living-related kidney donor: case report and review of the
      literature.
AB  - End-stage renal disease developed in a 37-year-old Saudi patient who donated a
      kidney to his brother 11 years previously. Biopsy of the remaining kidney showed
      focal-segmental glomerulosclerosis. Dialysis support was needed, and finally the
      patient received a living-nonrelated kidney transplant. The allograft function in
      the recipient brother remains very good 11 years after transplantation.

PMID- 8739289
TI  - Transient central diabetes insipidus in the setting of underlying chronic
      nephrogenic diabetes insipidus associated with lithium use.
AB  - Nephrogenic diabetes insipidus (NDI) is a well-documented complication of lithium
      use. The association of central diabetes insipidus (CDI) with lithium use is
      rare. We report a patient receiving chronic lithium therapy who presented with a
      transient CDI occurring in the setting of underlying chronic NDI. To the best of
      our knowledge, this is the first case of lithium-associated CDI and NDI
      presenting concurrently. Potential mechanisms regarding the pathophysiology of
      lithium-associated CDI are discussed. This case emphasizes the importance of the
      evaluation of lithium-associated polyuria with a direct measurement of plasma
      vasopressin, interpreted with simultaneous plasma and urine osmolality to secure
      the correct diagnosis and ensure appropriate therapeutic management.

PMID- 8739290
TI  - Severe calciphylaxis in a renal patient on long-term oral anticoagulant therapy.
AB  - The pathogenesis of calciphylaxis, a potentially life-threatening condition, is
      not well understood. Several factors such as end-stage renal disease (azotemia),
      hyperparathyroidism, hyperphosphatemia, hypercalcemia, a high calcium-phosphate
      product, and the use of steroids and cytotoxic drugs after kidney transplantation
      are believed to interact in calciphylaxis. Recently, hypercoagulability due to
      functional protein C deficiency has been suggested to play a pathogenic role in
      this condition. Here, we present a renal transplant patient, with secondary
      hyperparathyroidism and on long-term oral anticoagulant therapy, who developed
      calciphylaxis with severe skin necrosis of her legs. The patient's condition
      improved dramatically after total parathyroidectomy. Hypercoagulability,
      therefore, does not appear to have played a significant role in this case of
      calciphylaxis.

PMID- 8739291
TI  - Chronic hyponatremia due to reset osmostat in a patient with colon cancer.
AB  - A 62-year-old man with colon cancer who presented with hyponatremia is described.
      Volume depletion, renal failure, and cardiac, adrenal, hepatic, and thyroid
      diseases were excluded as causes of hyponatremia. The urine sodium concentration
      was repeatedly increased, suggesting the presence of the syndrome of
      inappropriate antidiuretic hormone secretion. An intact urinary diluting ability
      and the ability to maintain sodium balance without correcting hyponatremia when
      the sodium intake was high were consistent with the diagnosis of the reset
      osmostat variant of the syndrome of inappropriate antidiuresis.

PMID- 8739292
TI  - Novel frameshift mutation in a heterozygous woman with Fabry disease and end
      stage renal failure.
AB  - It is generally accepted that Fabry disease (angiokeratoma corporis diffusum) is
      an X-linked disorder resulting from the deficient activity of the lysosomal
      enzyme alpha-galactosidase. In males, the enzymatic defect leads to accumulation
      of glycosphingolipids, particularly in the kidney which causes end-stage renal
      disease. We report here a woman who presented in 1987 with focal and segmental
      glomerulosclerosis and required hemodialysis 4 years later when her son was
      evaluated for proteinuria. In these patients morphologic, biochemical, and
      genetic investigations were performed to explore the possibility of a hereditary
      renal disorder. Ultrastructural examination of the son's renal biopsy specimen
      revealed lamellated osmiophilic inclusions in the glomeruli, typical of Fabry
      disease. Four months after kidney transplantation in the mother, a graft biopsy
      specimen also revealed dense lamellated inclusions on electron microscopy. The
      leukocyte alpha-galactosidase activity was 0.008 mumol/min.10(9) cells in the son
      and 0.070 in the mother (range 0.100-0.500 mumol/min.10(9) cells). The diagnosis
      of Fabry disease was confirmed in both patients by the identification by DNA
      sequencing of a novel mutation in the alpha-galactosidase gene: one single base
      pair deletion in exon 3 (7317delA). IN CONCLUSION: (1) end-stage renal disease
      may occur in heterozygous women with Fabry disease; (2) morphologic lesions due
      to glycosphingolipid accumulation may be observed in the renal allograft after
      transplantation, and (3) DNA analysis confirmed the diagnosis by demonstrating a
      frameshift mutation, which has as yet not been reported.

PMID- 8739293
TI  - Visceral leishmaniasis in a renal transplant recipient: diagnostic and
      therapeutic problems.
AB  - Visceral leishmaniasis is infrequently reported in renal transplant recipients. A
      40-year-old renal transplant recipient developed hepatosplenomegaly and pyrexia
      of unknown origin 5 months after transplantation. Visceral leishmaniasis was
      confirmed on bone marrow examination. The usual dose of antiparasitic therapy
      with stibogluconate sodium failed to eradicate Leishmania donovani. High-dose
      conventional therapy with stibogluconate sodium for an extended period of time
      was successful in the treatment of a relapse of leishmaniasis.

PMID- 8739294
TI  - An interesting case of failed renal transplant complicated by a lymphocele
      infected with Pasteurella multocida and a review of the literature.
AB  - Lymphoceles are a well-known complication of renal transplant surgery and can be
      asymptomatic or present with a variety of symptoms and complications. We describe
      a patient who presented with a Pasteurella multocida infection of a lymphocele
      which occurred 3 weeks after a course of penicillin for a cat bite and 10 months
      after a renal transplant nephrectomy. We also will review the incidence,
      predisposing factors, origin, symptomatology, diagnosis, complications, and
      treatments of post-renal transplant lymphoceles.

PMID- 8739295
TI  - Evisceration of the eye in a renal transplant recipient with cytomegalovirus
      chorioretinitis.

PMID- 8739296
TI  - A new monoclonal antibody for specific immunocytochemical staining of nucleoli.
AB  - We have isolated a hybridoma cell line (clone 1E10) producing a monoclonal
      antibody which specifically recognizes nucleoli. The antibody (IgM, k isotype)
      was found to react in a nucleolar pattern with a variety of cell types. Specific
      staining was only obtained on cryostat sections of unfixed tissues. Paraffin
      embedding destroyed the epitope. Tissue specificity or species specificity was
      not observed. Nucleoli in neoplastic cells were highly reactive, presumably due
      to the larger size of nucleoli in these cells. Immunoelectron-microscopy (using a
      pre-embedding as well as a post-embedding technique) confirmed the specific
      nucleolar localization of the immunoreactivity. Immunoreactivity was confined to
      the granular component of the nucleolus. The intensity of the immunoreactivity
      increased after cell or tissue pretreatment with DNase, pronase or trypsin,
      indicating that the target epitope is not DNA or a protein. On Western blots of
      immunoreactive cells no specific signal was obtained, which supports the non
      protein nature of the epitope. Acid hydrolysis and RNase digestion abolished the
      immunoreactivity. Parallel staining experiments with methylgreen pyronin and
      acridin orange confirmed the RNA nature of the epitope. In spot blots,
      immunoreactivity was not found with tRNA or mRNA. These observations indicate
      that 1E10 recognizes a conformational RNA epitope which occurs only in the
      nucleolus.

PMID- 8739297
TI  - An immunocytochemical analysis of growing axons in a silicone chamber prefilled
      with artificial sponge matrix.
AB  - We have used antibodies against growth associated protein (GAP-43),
      phosphorylated neurofilament protein of 200 kDa molecular weight (RT-97) and
      substance P (SP) to analyze regrowing axons and their features in a silicone
      chamber filled with resorbable sponge matrix within the first two weeks after
      sciatic nerve transection in the rat. Growing axons identified with the GAP-43
      antibody extended over a distance of about 7 mm from the proximal stump at 7 days
      and grew over a 10 mm gap within, 14 days. This is a markedly longer distance
      than in the case of the standard chamber model without artificial sponge matrix.
      The regrowing axons were labelled with RT-97 already on the 7th day up to a
      distance of 5 mm and they made up about 75% of all axons in the first segments.
      The number of RT-97-positive axons did not increase significantly over the next 7
      days, although they could be identified over a longer distance. Some of the
      growing axons expressed SP-like immunoreactivity (LI) 14 days, but not 7 days
      after chamber application and constituted about 30% of all growing axons in the
      first segment. The SP-LI fibres also appeared to grow from the distal stump since
      they were found in larger numbers in the distal segments than in central ones.
      Those fibres accompanying blood vessels are probably sympathetic. Our findings
      demonstrate that axons are able to bridge a 10 mm gap within 14 days under
      appropriate substrate conditions, which are provided by the resorbable fibrin
      sponge.

PMID- 8739298
TI  - Expression and immunohistochemical localization of eight phospholipase C isoforms
      in adult male mouse cerebellar cortex.
AB  - By means of specific polyclonal or monoclonal antibodies we have investigated the
      expression and the localization of phospholipase C isoforms in the adult mice
      cerebellar cortex. Western-blot analysis revealed that mouse cerebellum expressed
      eight phospholipase C isozymes: -beta 1, -beta 2, -beta 3, -beta 4, -gamma 1, 
      gamma 2, -delta 1, -delta 2. Immunohistochemical analysis carried out on
      cryosections showed a distinct pattern of expression for each of the isoforms.
      Purkinje cells had high levels of -beta 1, -beta 3, -gamma 2 and -delta 2
      isotypes. The -gamma 2 isozyme was the only one that was identified also in the
      dendrites of Purkinje cells. In the molecular layer we detected mostly -beta 1
      and -gamma 1 isozymes whereas in the granular layer -gamma 1 and -gamma 2
      isoforms prodominated. These results indicate a heterogeneity of the
      phospholipase C isoforms expressed in the layers of mouse cerebellar cortex
      conceivably due to the fact that these enzymes are coupled to different receptors
      and perform selective tasks in regulating cell signalling events taking place in
      the cerebellar cortex of mice.

PMID- 8739299
TI  - Quantitative enzyme- and immunohistochemistry of hexokinase and cytochrome c
      oxidase of spinal neurons in the zebrafish.
AB  - A combined quantitative enzyme- and immunohistochemical procedure to demonstrate
      hexokinase (HK) was developed and tested on sections of spinal cord tissue of the
      zebrafish. In both procedures, the amount of final reaction product was linearly
      related with section thickness. When applied to serial sections of fish spinal
      neurons, the enzyme- and immunohistochemical activities appeared to correlate
      significantly (r = 0.61; p < 0.001). As HK and cytochrome c oxidase (COX)
      histochemistry have been used regularly to screen the average level of chronic
      activity of neurons, we subsequently analysed the relationship between HK and COX
      in fish spinal neurons, using previously published methods of quantitative enzyme
      and immunohistochemistry for COX. The enzyme- as well as the immunohistochemical
      localisation patterns of HK showed a weak correlation with the enzyme- and
      immunohistochemical COX localisation respectively. Therefore, it is concluded
      that both enzyme- and immunohistochemical localisation of COX provide a poor
      estimate for the relative level of glucose utilisation in fish spinal neurons.

PMID- 8739300
TI  - Immunocytochemical demonstration of androgen receptors in Leydig cells of the
      bank vole (Clethrionomys glareolus, Schreber): an in vitro study.
AB  - Androgen receptors of the bank vole Leydig cells in vitro were immunostained
      using a polyclonal antibody against androgen receptors followed by streptavidine
      peroxidase complex or rhodamine-labelled goat anti-rabbit IgG visualization. The
      immunocytochemical studies revealed localization of androgen receptors in the
      whole cytoplasm or in the perinuclear area of the cells. Addition of
      dehydroepiandrosterone into the culture medium resulted in nuclear localization
      of the androgen receptors. Long (18L : 6D) and short (6L : 18D) photoperiods as
      well as the age of animals were taken into account. The concentration of androgen
      receptors was changed dependent on age and status of reproduction.

PMID- 8739301
TI  - Internalization of wheat germ agglutinin (WGA) by rat pancreatic cells in vivo
      and in vitro.
AB  - The uptake of the lectin wheat germ agglutinin (WGA) by the rat pancreas was
      studied after intraperitoneal injection of FITC-labelled WGA. Strong fluorescence
      was seen in the interstitial space of the pancreatic parenchyma and on the
      basolateral surface of acinar cells after one h. Two or four h after injection
      there was also a fluorescence inside the acinar cells. After intraparenchymal
      injection of colloidal gold-labelled WGA into the pancreatic gland in situ or in
      vitro incubation of isolated rat pancreatic acinar cells with WGA-gold, an
      internalization of the lectin by receptor mediated endocytosis was observed
      electron microscopically. Clathrin-coated pits or vesicles could not be observed.
      The results suggest a direct uptake of WGA from the peritoneum into the gland by
      diffusion and its binding as well as internalization by the pancreatic acinar
      cells.

PMID- 8739302
TI  - Nitric oxide synthase I immunoreactivity and NOS-associated NADPHd histochemistry
      in the visceral epithelial cells of the intraplacental mouse yolk sac.
AB  - In the course of our studies on the local blood flow modulation in the NMRI-mouse
      placenta we have focussed on regulatory pathways involving recently appreciated
      gaseous messenger molecules nitric oxide (NO) and carbon monoxide (CO), which are
      generated by NO synthase (NOS) and heme oxygenase (HO)-2, respectively. The
      distribution of NOS was investigated by immunohistochemistry using an antiserum
      to the neuronal isoform (NOS-I) and by NADPH diaphorase (NADPHd) histochemistry,
      supplemented with procedures (permanganate and formaldehyde method) serving to
      enhance the specificity of the enzyme histochemical method for NOS visualization.
      HO-2 was demonstrated immunohistochemically. In addition, cyclic guanosine
      monophosphate (cGMP)-forming soluble guanylate cyclase (sGC) and dehydrogenases
      generating the NOS co-substrate NADPH were analysed either by
      immunohistochemistry or enzyme histochemistry. NOS-I immunostaining was observed
      in the intraplacental visceral yolk sac epithelial cells but not in the placenta
      and extraplacental visceral epithelial yolk sac cells. Co-localization of NOS-I
      immunolabeling and NOS-associated NADPHd was exclusively found in the
      intraplacental visceral epithelial cells, while NADPHd activity not associated to
      NOS was present in other placental and extraplacental cells additionally analysed
      for control reasons. HO-2 and sGC immunoreactivity could not be detected in the
      placenta including the intraplacental visceral epithelial cells but were
      expressed in several extraplacental cells. Dehydrogenases producing the NOS co
      substrate NADPH were present in the intraplacental visceral epithelium as well as
      in other placental and extraplacental cells. Since the intraplacental visceral
      epithelial yolk sac layer closely accompanies large fetal blood vessels entering
      the placental labyrinth from the chorionic plate it may be assumed that NO,
      generated by the NADPH-consuming NOS-I in the intraplacental yolk sac epithelium,
      acts to regulate the blood flow by relaxing smooth muscle cells in the wall of
      these fetal vessels. The lack of immunoreactivity to the NO-effector molecule sGC
      may be due to methodological reasons. The absence of the HO-2/CO system suggests
      its insignificant role as a potential gas signaling pathway in the vascular
      smooth muscle system of the intraplacental visceral yolk sac of mice.

PMID- 8739303
TI  - VCAM-1 expression and network of VCAM-1 positive vascular dendritic cells in
      advanced atherosclerotic lesions of carotid arteries and aortas.
AB  - This study was undertaken to determine whether vascular dendritic cells (VDCs)
      display VCAM-1 in atherosclerotic lesions. Specimens of carotid artery and aorta
      were obtained at operation. All the plaques contained VCAM-1+ cells, but VCAM-1
      immunoreactivity was irregularly distributed being mainly associated with the
      zones of neovascularisation in the base of the atherosclerotic plaques. Vascular
      dendritic cells were identified with DAKO-CD1 a. Alternative parallel sections
      were stained with either anti-CD1 a or anti-VCAM-1. By comparison of consecutive
      parallel sections the CD1a+ vascular dendritic cells were located separate from
      other intimal cells. In some areas networks formed by VCAM-1+ vascular dendritic
      cells were observed suggesting that cellular networks may mediate a local immune
      response in atherosclerotic lesions. We speculate that VCAM-1 is involved in the
      formation of cell-to-cell contacts of vascular dendritic cells in atherogenesis.

PMID- 8739304
TI  - Immunohistochemical localization of basic fibroblast growth factor, platelet
      derived growth factor, transforming growth factor-beta and tumor necrosis factor
      alpha in the pterygium.
AB  - Some fibroangiogenic factors have recently been shown to play potential roles in
      fibrovascular diseases. The aim of this study was to examine whether there is any
      relationship between growth factors and pterygium genesis. Twenty-three primary
      pterygia and 4 normal conjunctiva specimens were analyzed by indirect
      immunohistochemistry using specific antibodies against basic fibroblast growth
      factor (b-FGF), platelet derived growth factor (PDGF), transforming growth factor
      beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha). Positive
      immunostaining of these growth factors was located in the epithelial cells,
      endothelial cells of vessels, basement membranes of vessels and epithelium,
      fibroblasts and infiltrating inflammatory cells in the pterygium. In the normal
      conjunctiva, positive immunolabeling for TGF-beta and PDGF was much weaker than
      in the pterygium. We conclude that growth factors may interact directly or
      indirectly in the pathogenesis of pterygium although proof of this awaits further
      studies.

PMID- 8739305
TI  - Expression of heme oxygenase-2 (HO-2)-like immunoreactivity in rat tissues.
AB  - Microsomal heme oxygenase (HO) is a cytochrome P-450-assisted oxidoreductase,
      which catalyzes the NADPH-dependent decomposition of heme to carbon monoxide
      (CO), biliverdin, and iron. Recent evidence suggests that CO, similar to nitric
      oxide (NO), may serve as gaseous biological signalling molecule, which acts by
      stimulating soluble guanylate cyclase in target cells. In the present
      investigation, we report the HO-like immunoreactivity (LIR) pattern of the
      constitutive HO isozyme, HO-2, and compare the results with recently published
      data on constitutive NO-producing nitric oxide synthase (NOS) in rat tissues. HO
      2-LIR was most consistently observed in connective tissue elements (fibrocytes/
      blasts and fibroblast-like cells, such as interstitial cells in the bowel), blood
      vessel wall constituents (arterial and venous endothelial cells, vascular smooth
      muscle cells), visceral smooth muscle cells (airway musculature, myometrium,
      muscularis mucosae of the small intestine), mesothelial cells of serous membranes
      and in select epithelial cell populations. HO-2-LIR was absent from the striated
      (skeletal and cardiac) musculature. HO-2 had a more widespread distribution and
      its expression largely differs from that of NOS. HO-2-LIR and NOS appear to be co
      expressed in vascular endothelial cells and in selected nerve cell populations of
      certain parasympathetic and probably sensory ganglia. Our data suggest potential
      CO and NO systems as interrelated regulatory pathways in the local paracrine and
      autocrine control of diverse functional systems.

PMID- 8739306
TI  - The use of substrates with 7-amino-3-trifluoromethylcoumarine (AFC) leaving group
      in the localization of protease activities in situ.
AB  - A method for the localization of activities of proteases using substrates with 7
      amino-3-trifluoromethylcoumarine (AFC) leaving group is described. 0.1 ml of 5-20
      mMol solution of the respective substrate (Gly-Pro-AFC, Ala-Pro-AFC, Z-Ala-Arg
      Arg-AFC, Z-Gly-Arg-Arg-AFC, Z-Gly-Gly-Arg-AFC, D-Val-Leu-Lys-AFC) in
      dimethylsulfoxide or dimethylformamide was added to 0.9 ml of 0.1 M Tris-HCl
      buffer, pH 7.4-7.8 or 0.1 M cacodylate buffer, pH 5-5.5. In the case of Z-Ala-Arg
      Arg-AFC (cathepsin B substrate) 15 mM EDTA and 12 mM dithiothreitol were added. 7
      mM amiloride or 2 mg/1 ml aprotinin were used as inhibitors with Z-Gly-Gly-Arg
      AFC (urokinase substrate) and with D-Val-Leu-Lys-AFC (plasmin substrate).
      Substrate solutions were mixed with an equal amount of 2% agar solution in
      distilled water or in the respective buffer the pH of which was adjusted
      according to the pH optimum of the enzyme to be demonstrated. The agar solution
      was kept in a water bath at a temperature of 50-60 degrees C. After careful
      mixing, the substrate solution in agar was poured into a cylindrical vessel
      closed with a semipermeable membrane (Nephrophan) on which unfixed cryostat
      sections were mounted. 1-5 mM AFC solution in dimethylsulfoxide or
      dimethylformamide instead of the substrate was used as the control. Quenched
      samples of rat kidney and jejunum, biopsies of human jejunal mucosa, and of
      colorectal and uterine tumors were employed for the preparation of sections.
      After gelification of the medium in a refrigerator the vessels with sections were
      incubated in the dark at 37 degrees C for 0.5-several h. The reaction was
      controlled in a fluorescence microscope with an epiillumination adjusted to the
      FITC fluorescence and documented. A yellowish green fluorescence depicts sites
      where AFC was set free (sites with enzyme activity). When the reaction reached
      the required intensity the membranes were cut off, transferred to glass slides,
      mounted in glycerol, observed and photographed immediately (due to the solubility
      of AFC in glycerol). An acceptable cellular localization was achieved. The method
      with AFC substrates can be recommended for comparative biochemical and
      histochemical studies of proteases using the same substrate and for cases in
      which no other reliable procedure for the localization of the respective enzyme
      activity is available (e.g. urokinase, plasmin).

PMID- 8739307
TI  - Comparison of the islet cell antibody pattern of monoclonal glutamic acid
      decarboxylase antibodies recognizing linear and conformational epitopes.
AB  - In order to compare the reactivity of glutamic acid decarboxylase (GAD)
      antibodies recognizing linear and conformational epitopes as islet cell
      cytoplasmic antibodies (ICA), monoclonal antibodies were generated. An ELISA
      displacement test using two biotinylated monoclonals recognizing a linear
      (M61/7E11) or a conformational GAD65 epitope (M65/6B12) was performed to identify
      epitope regions recognized by monoclonal GAD antibodies. The GAD binding by
      monoclonal GAD antibodies was tested by immunofluorescence on fixed and unfixed
      pancreatic sections of human, rat, and mouse, and by Dot-blot experiments. 16/23
      (69.6%) of the monoclonals were specifically reactive with GAD65 and 7/23 (30.4%)
      were reactive with both GAD isoforms. 8/16 (50%) of monoclonal GAD65 antibodies
      recognized a linear GAD epitope located at the N-terminus (pattern 1). 5/16
      (31.3%) displaced M65/6B12, indicating the recognition of a conformational GAD
      epitope (pattern 2). Monoclonals belonging to patterns 1 and 2 showed strong ICA
      binding. 3/16 (18.8%) of monoclonals specific for GAD65 with weak or no
      immunostaining of pancreatic islets (pattern 3) did not inhibit the binding of
      both biotinylated antibodies in the displacement test, indicating other epitope
      specificities. In conclusion, GAD antibodies recognizing both conformational and
      linear epitopes of the GAD65 molecule are involved in ICA binding with strong
      reactivity. Furthermore, results obtained with monoclonals of pattern 3 suggest
      the occurrence of GAD65 epitopes partly inaccessible on cryosections, which may
      result in an ICA-negative test of GAD65 autoantibody positive sera.

PMID- 8739308
TI  - Modulation of lipopolysaccharide-induced tumor necrosis factor-alpha and nitric
      oxide production by dopamine receptor agonists and antagonists in mice.
AB  - The effects of various agonist and antagonists of dopamine D1 and D2 receptors on
      lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) and
      nitric oxide (NO) production was investigated in mice. Pretreatment of animals
      with bromocryptine or quinpirole, agonists of dopamine D2 receptors caused a
      blunting of both the TNF-alpha and NO responses to LPS injected
      intraperitoneally. Sulpiride, an antagonist of dopamine D2 receptors, decreased
      the LPS-induced TNF-alpha plasma levels in a dose-dependent manner and inhibited
      the LPS-induced NO production by peritoneal macrophages. Bromocryptine or
      quinpirole blunted both the TNF-alpha and NO response to LPS. SCH-23390, an
      antagonist of dopamine D1 receptors did not alter LPS-induced TNF-alpha
      production, but inhibited LPS-induced NO production. These results indicate that
      while the D2 subtype of dopamine receptors is involve in the modulation of both
      LPS-induced TNF-alpha and NO production, dopamine D1 receptors only regulate the
      production of NO. Since several drugs possess effect on dopamine D2 receptors,
      the present observations may be of clinical relevance.

PMID- 8739309
TI  - Binding of mutated Ras- and p53-derived peptides to HLA-DR molecules.
AB  - We investigated binding of p53- and Ras-derived peptides with frequently observed
      missense mutations, to various L cell transfectants expressing a single species
      of HLA-DR complex, and found that: (i) all the synthetic peptides bound to
      various DR complexes with a variable affinity; (ii) some DR allelic products had
      a high affinity for both p53- and Ras-derived peptides (e.g., DRB1*1502), whereas
      others almost no affinity (e.g., DRB1*1101); and (iii) DR-binding motifs
      described in the literature can explain some of the allele-specific interactions
      between mutated peptides and DR complexes. Therefore, some mutated Ras- and p53
      derived peptides could be tumor-specific antigens recognized by CD4+ T cells in
      an HLA-DR allele-specific manner.

PMID- 8739310
TI  - Human-->mouse radiation chimera do not develop Epstein-Barr virus lymphoma.
AB  - It has been shown that engraftment of human peripheral blood lymphocytes (PBL)
      from Epstein-Barr virus (EBV) seropositive donors in C.B-17/SCID mice is
      associated with a high incidence of human B cell tumors. More recently, we
      described a new approach enabling engraftment of human PBL in normal strains of
      mice or rats receiving lethal split-dose radiation and radioprotected with SCID
      bone marrow. We now demonstrate that, in contrast to SCID recipients of human
      PBL, Balb/c and C3H/HeJ recipients of 50-100 x 10(6) human PBL did not develop
      any EBV lymphoma during a 7-month follow-up period, but were successfully
      engrafted with human B and T cells. On the other hand, lymphoma developed in 90%
      of the C.B-17/SCID mice infused with 70 x 10(6) human PBL from the same donor.
      Likewise, 36% of beige/nude/xid (BNX) mice, exposed to 12 Gy TBI, radioprotected
      with SCID bone marrow and then transplanted with human PBL developed lymphoma.
      Similar results were obtained when different strains were infused with PBL of the
      same donor. Immunohistochemical analysis indicated that the tumor cells were of
      human B cell origin and expressed the EBV-encoded latent membrane protein-1 and
      nuclear antigen 2. While further studies are required to understand the
      mechanisms which suppressed outgrowth of EBV lymphoma in human --> mouse
      radiation chimera, compared to human --> C.B-17/SCID or human --> BNX chimera,
      this marked resistance offers new possibilities for transplantation of
      hematopoietic tissues or cells from EBV-positive donors.

PMID- 8739311
TI  - The influence of T cell subsets on Trypanosoma cruzi multiplication in different
      organs.
AB  - Several studies in mice have strengthened the active role played either by CD4+,
      CD8+ or both T cell subsets in conferring resistance to Trypanosoma cruzi
      infection. To date, no studies reported the role played by T cell subsets on
      parasite multiplication in different organs. In the present work, mice were
      infected with CL strain of T. cruzi and T cell subset activities were blocked by
      i.p. injection of monoclonal antibody (mAb) directed against CD4, or IAk, or CD8
      molecules. The effect of these treatments was determined by counting the number
      of parasite nests in heart and liver sections 16 days after infection. Our
      results showed that mice treated with anti-CD4 or anti-IAk mAbs presented a
      significant increase in the parasite load in the hearts and in the livers.
      Conversely, the number of parasites in hearts of anti-CD8 treated mice did not
      increase significantly. This treatment, however, resulted in a 20-fold increase
      in the number of parasites found in the liver. Simultaneous depletion of both T
      cell subsets by treatment of mice with anti-CD4/CD8 mAbs had, in the heart, the
      same effect as the CD4 depletion. Interestingly, this treatment caused a dramatic
      increase (200-fold) in the T. cruzi parasitism of the liver. These results
      indicate that the activity of T cell subsets against T. cruzi varies according to
      the infected organ.

PMID- 8739312
TI  - Quantitative and realtime correlation between receptor aggregation and
      intracellular calcium signal transduction.
AB  - Quantitative correlation between intracellular calcium signals and hapten density
      or molecular size of antigens was studied for two cell lines; hapten-specific
      murine B cells (TP67.21) and rat basophilic leukemia cells (RBL-2H3) with hapten
      specific IgE. Magnitude of the induced calcium signal in both cells exhibited the
      same dependence on hapten density of antigen molecules and there existed an
      optimal hapten density which induced the maximum amount of calcium signal for
      both cells. However, they responded differently to antigens of various molecular
      size. In contrast to TP67.21 cells which showed larger response to larger antigen
      molecules, RBL-2H3 cells showed the largest response to the smallest antigen.
      This may possibly suggest that there exists an optimal structure of receptor
      aggregates for each cell. Calcium signal induced in each cell by multivalent
      antigen was rapidly abrogated by addition of excess hapten and this abrogation
      occurred both in transmembrane influx and the release from intracellular stores.
      We directly observed the mobilization of receptor molecules during this calcium
      signal abrogation at single cell level by using two fluorescent calcium probes,
      whose fluorescence wavelength ranges have least overlap, and confocal microscopy.
      During this abrogation, large clusters of receptor molecules were not affected by
      hapten molecules. We, therefore, conclude that these large clusters are inactive
      in the induction of calcium signal and smaller clusters of receptor molecules are
      necessary for calcium signal induction.

PMID- 8739313
TI  - Human mannan binding protein in pre-eclampsia.
AB  - Mannan binding protein (MBP) was measured in the sera of 95 patients with
      proteinuric pre-eclampsia and in 76 sera from the husbands of those patients. No
      significant difference was found in comparison with 352 blood donors. However,
      couples experiencing recurrent pre-eclampsia had significantly lower levels of
      MBP than those associated with primiparous couples with pre-eclampsia. The latter
      finding was derived from data inspection and not from a prior hypothesis, and
      therefore requires independent confirmation preferably from a larger series.

PMID- 8739314
TI  - Generation of TNF alpha, IFN gamma, IL-6, IL-4 and IL-10 in mouse serum from
      trichinellosis: effect of the anti-inflammatory compound 4-deoxypyridoxine (4
      DPD).
AB  - Infections caused by the nematode Trichinella spiralis is characterized in the
      host by an inflammatory response with cytokine production. In these studies we
      have detected TNF alpha, IL-6, IFN gamma, IL-4 and IL-10 in the serum of 10 mice
      infected with T. spiralis. Moreover, we detected, for the first time, these
      cytokines in the serum of mice treated with 4-DPD, a potent antagonist of vitamin
      B6 coenzyme which has anti-inflammatory properties. 4-DPD was used at 100, 400,
      800 micrograms/bolus for 20 days, starting one day before the infection. After 15
      days of T. spiralis infection, TNF alpha reached a maximum level, while IL-6 was
      maximal after 7 days, IFN gamma at 20 days and IL-4 at 14 days. IL-10 was not
      affected by the T. spiralis infection. When the animals were treated with 4-DPD
      at the reported dosages and infected with T. spiralis the inhibition of TNF alpha
      and IL-6, were dose-dependent in the first 7 days while IL-4 was reduced only at
      400-800 micrograms/bolus. 4-DPD-treated mice did not statistically (P > 0.05)
      affect the generation of IFN gamma. In healthy animals the production of
      cytokines were not measurable, just as it was in non-infected animals treated
      with 4-DPD. The increase of cytokines such as, TNF alpha and IL-6 may be related
      to the severity of the disease, boosting the host's resistance to the pathogen
      and inhibiting parasite survival. In addition, the augmentation of IL-4
      production enhances T and B cells and macrophage responses and may stimulate T
      cell antibody-mediated response to the pathogen. 4-DPD, an inhibitor of IL-1 and
      inflammatory reactions, proved to be most effective on TNF alpha and IL-6, which
      are mainly produced by macrophages.

PMID- 8739315
TI  - Immunodominant synthetic peptides of Taenia crassiceps in murine and human
      cysticercosis.
AB  - The screening of a cDNA library of Taenia crassiceps revealed a clone designated
      KETc7 that induced high levels of protection against murine cysticercosis in
      previous experiments. The molecular structure of the deduced 100-amino acid
      sequence of the corresponding proline-rich polypeptide was studied to detect
      potentially immunologically active epitopes. Several candidate epitopes were
      identified, three of which were synthesized by solid-phase peptide synthesis and
      used as antigens in enzyme-linked immunosorbent assay (ELISA) for detection of
      specific antibodies in a selected panel of sera from mice infected with Taenia
      crassiceps and pigs infected with Taenia solium, as well as in the serum and
      cerebrospinal fluid of human patients with neurocysticercosis. The three peptides
      detected antibodies in serum from all infected mice. Seven of nine sera from
      patients with neurocysticercosis reacted strongly with peptide GK-3, and four of
      them with peptides GK-1 and GK-2. A lower reactivity was observed in sera from
      experimentally infected pigs. Peptide GK-3 reacted also with 45 out of 77
      cerebrospinal fluids (CSF) from patients with confirmed neurocysticercosis and
      with 14 out of 68 CSF from control patients with other neurological disorders.
      This is the first report on synthetic peptides that are prominent in the humoral
      response of murine, porcine and human cysticercosis. Their identification implies
      finer molecular tools in the exploration of this form of host-parasite
      relationship, as well as hints to their application in immunodiagnosis and in
      vaccine design.

PMID- 8739316
TI  - Mechanisms of simian gamma delta T cell cytotoxicity against tumor and
      immunodeficiency virus-infected cells.
AB  - The mechanisms of cytotoxic killing of various tumor cell lines and
      immunodeficiency virus-infected T cell lines by simian gamma delta T cells were
      examined. The lysis of the majority of the target cell lines by gamma delta
      effectors was calcium-dependent, indicating that cytotoxicity is mediated by the
      perforin/granzyme pathway rather than the Fas-FasL pathway, with the exception of
      Jurkat cells. The gamma delta T cells were able to suppress SIV replication as
      measured by the p27 ELISA and the suppression was contact-dependent. We further
      determined that the target cells were induced to undergo apoptosis by the gamma
      delta T cell effectors. These results contribute to our understanding of the
      function of simian gamma delta T cells and their similarities to human gamma
      delta T cells, and extend our knowledge on the cytotoxic mechanisms employed by
      gamma delta T cells in general.

PMID- 8739317
TI  - P2x purinoceptor is not important in thymocyte apoptosis.
AB  - Since the P2X purinoceptor has been shown to be homologous with RP-2, a gene
      activated in thymocytes undergoing apoptosis after glucocorticoid treatment, we
      have investigated the possible role of P2X purinoceptors in thymocyte apoptosis.
      We report that P2X purinoceptor mRNA is expressed both in untreated rat
      thymocytes and thymocytes treated with the synthetic glucocorticoid, 6 alpha
      methylprednisolone, in a dose that can induce apoptosis. Furthermore, the P2X
      receptor agonist, extracellular ATP, was unable to trigger apoptosis in rat
      thymocytes and had no effect on methylprednisolone-induced DNA fragmentation.
      Finally, the P2X purinoceptor antagonist, suramin and pyridoxalphosphate-6
      azophenyl-2',4'-disulfonic acid, had no inhibitory effects on DNA fragmentation
      caused by methylprednisolone. Thus, our data demonstrate that P2X purinoceptors
      are not directly involved in glucocorticoid-mediated thymocyte apoptosis.

PMID- 8739318
TI  - Angiotensin II--an important stress hormone.
AB  - Angiotensin II (Ang II) is an important stress hormone. Circulating and tissue
      Ang II are significantly increased in both acutely and chronically stressed
      animals. In humans, the plasma Ang II content increases markedly after sprinting,
      as does cortisol. The present paper reviews recent studies with special reference
      to the correlation between the renin-angiotensin system (RAS) and the
      hypothalamus-pituitary-adrenal cortex system and sympathetic-adrenal medulla
      system during stress. We would like to suggest that in the stress response, Ang
      II is not only a stress hormone to various peripheral organs, but is also a
      notable factor in initiating the systemic stress response from central to
      peripheral tissues. The RAS is therefore a stress hormone response system similar
      to the hypothalamus-pituitary-adrenal cortex system and the sympathetic-adrenal
      medulla system.

PMID- 8739319
TI  - Expression cloning and signal transduction pathway of P2U receptor in mammary
      tumor cells.
AB  - Extracellularly applied ATP, UTP and UDP induce a transient increase in the
      intracellular Ca2+ concentration of mammary cells via a P2U receptor. The P2U
      receptor in the mammary tumor cell line MMT060562 was cloned and expressed in the
      human leukemia cell line K-562. The deduced amino acid sequence of the mammary
      tumor cell P2U receptor was 98% homologous with that of mouse NG108-15 cells. It
      was a member of the superfamily of GTP-binding-protein-coupled receptors. ATP and
      UTP induced the increase in the intracellular concentrations of Ca2+ and inositol
      1,4,5-trisphosphate in both mammary tumor cells and P2U-receptor-expressed K562
      cells. Dose-response curves on the production of inositol-1,4,5-trisphosphate and
      Ca2+ by ATP and UTP were consistently similar. Injection of GTP enhanced the ATP
      induced outward current and injection of GTP gamma S induced a repetitive outward
      current. Both pertussis and cholera toxins did not affect ATP-induced calcium
      increase. It was suggested that the P2U receptor coupled with pertussis- and
      cholera-toxin-insensitive GTP-binding proteins and activated phosphoinositide
      turnover.

PMID- 8739320
TI  - Effects of dibutyryl cAMP and bacterial toxins on indoleamine-induced encystment
      of dinoflagellates.
AB  - Dinoflagellates are the causative agents of red tides with worldwide occurrence
      and can be induced to encyst by in doleamines such as melatonin and 5
      methoxytryptamine (5-MOT). This biological response may be mediated via
      indoleamine-binding proteins or receptors. Here we report the initial
      characterization of the signal transduction mechanisms by which indoleamines
      induce encystment of dinoflagellates. In particular, we explored the possible
      involvement of G proteins and cAMP in cyst formation. Both melatonin and 5-MOT
      promoted the encystment of Gonyaulax tamarensis and Crypthecodinium cohnii.
      Exposure of dinoflagellates to dibutyryl cAMP, which directly activates cAMP
      dependent pathways, did not affect the ability of indoleamines to promote
      encystment. However, dibutyryl cAMP dose-dependently diminished the indoleamine
      induced suppression of cell growth. Exposure of dinoflagellates to the bacterial
      toxins from Vibrio cholerae and Bordetella pertussis had no effect on the
      indoleamine-induced encystment response, indicating the lack of involvement of Gs
      or Gi-like proteins. Moreover, [32P]ADP ribosylation of dinoflagellate membranes
      by either toxin failed to identify substrate proteins. These results suggest that
      although the indoleamine-induced encystment of dinoflagellates may involve a G
      protein-coupled signal transduction pathway, the identity of the G protein
      concerned may be distinct from those that regulate adenylyl cyclases in mammalian
      cells.

PMID- 8739321
TI  - Temperature dependence of processes proximal and distal to the glucose-induced
      [Ca2+]i rise in stimulus-secretion coupling in rat pancreatic islets.
AB  - Cooling is known to inhibit glucose-induced insulin secretion from pancreatic
      islets, but temperature-dependent processes in stimulus-secretion coupling remain
      unclear. In the present study, we examined the effects of cooling on the glucose
      induced increase in cytoplasmic Ca2+ concentration ([Ca2+]i) and concomitant
      insulin secretion in rat pancreatic islets to analyze the temperature dependence
      of processes proximal and distal to the Ca2+ signal in stimulus-secretion
      coupling. Rat pancreatic islets were isolated and perifused. [Ca2+]i was measured
      using fura-2. Glucose (15 mM) caused a triphasic [Ca2+]i response in single
      islets at 35 degrees C: an initial decrease and a transient increase followed by
      a gradual increase, on which series of Ca2+ transients were frequently
      superimposed. Cooling to 30 and 25 degrees C caused slower and smaller [Ca2+]i
      responses with a Q10 (temperature coefficient) of 1.8. Glucose caused biphasic
      insulin secretion at 35 degrees C, which was inhibited by cooling, with a Q10 of
      11.6. The ratio of glucose-induced insulin secretion to [Ca2+]i rise (IS/Ca) was
      calculated to represent the efficiency of Ca2+ to cause exocytosis. The Q10 value
      of the ratio of IS/Ca was 6.6. The Q10 values of the ratio of IS/Ca in the
      responses to high K+ (30 mM), carbamylcholine (100 microM) and glibenclamide (2
      microM) were 5.6, 3.8, and 13.0, respectively. These values were greater than the
      Q10 values of corresponding [Ca2+]i responses: 1.2, 1.4, and 1.8, respectively.
      From these results, we conclude that cooling inhibits not only the glucose
      induced [Ca2+]i rise but also Ca(2+)-activated exocytosis, and that the latter is
      much more sensitive to cooling than the former.

PMID- 8739323
TI  - Effect of some anticancer drugs and combined chemotherapy on renal toxicity.
AB  - The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG),
      methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered
      alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on
      Wistar rats. After drug administration, creatinine concentrations in the plasma
      and in the urine of the rats were determined, as well as creatinine clearance.
      Histopathologic evaluation of the kidneys was also performed. After MTX
      administration a significant increase (p = 0.0228) in the plasma creatinine
      concentration and a significant (p = 0.0001) decrease in creatinine clearance was
      noted compared to controls. After the administration of NG, 5-FU and CY neither a
      statistically significant increase in creatinine concentration nor an increase in
      creatinine clearance was observed compared to the group receiving no cytostatics.
      Following polytherapy according to the CMF regimen, a statistically significant
      decrease (p = 0.0343) in creatinine clearance was found, but creatinine
      concentration did not increase significantly compared to controls. CY caused
      hemorrhagic cystitis in 40% of rats, but it did not cause this complication when
      combined with 5-FU and MTX. Histologic changes were found in rat kidneys after
      administration of MTX, CY and NG, while no such change was observed after 5-FU
      and joint administration of MTX + 5-FU + CY compared to controls. Our studies
      indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower
      than in monotherapy.

PMID- 8739322
TI  - Pituitary contents of beta-endorphin, dynorphin, substance P, cholecystokinin and
      somatostatin in rats with streptozotocin-induced diabetes.
AB  - The effects of streptozotocin-induced diabetes on pituitary neuropeptides were
      studied. Substance P, dynorphin and beta-endorphin in both pituitary lobes and
      cholecystokinin and somatostatin in the neurointermediate lobe (NIL) were
      measured 4 weeks after streptozotocin treatment in adult male rats. There were
      significant decreases of substance P levels in both the anterior lobe (AL) and
      NIL, and of cholecystokinin, dynorphin and beta-endorphin in the NIL, whereas the
      dynorphin content in the AL increased, when values were expressed on a per-lobe
      basis. On a per-milligram-protein basis, however, only beta-endorphin in the NIL
      showed a significant decrease, while AL beta-endorphin and dynorphin were
      increased. Correlated with these changes were a drastic decrease in the serum
      insulin level and a marked increase in serum glucose and corticosterone levels.
      All these changes were reversible with insulin treatment. It is suggested that
      the decrease in NIL contents of neuropeptides demonstrated (except for beta
      endorphin) might be due to mechanisms other than a change in synthesis.

PMID- 8739324
TI  - Selective loss of the CD4+/CD26+ T-cell subset during HIV infection.

PMID- 8739325
TI  - The primary antibody repertoire of normal, immunodeficient and autoimmune mice is
      characterized by differences in V gene expression.
AB  - During the last decade, the structure and organization of the immunoglobulin
      heavy and light chain locis have been defined in mice and humans. Studies on VH
      gene expression at different stages of development, in different organs and
      disease states have provided useful insight into the construction of a primary
      antibody repertoire in mice. Clearly, 3'VH genes 7183, Q52 and Vh11, which are
      conserved during evolution, are preferentially expressed during early development
      of the B-lymphocyte repertoire. A preferential use for the V kappa 4 gene family
      is evident during early B-cell development. The initial development of the
      primary antibody repertoire is therefore influenced by a restricted set of VH and
      V kappa gene elements. The restricted B-cell repertoire is subsequently
      normalized in the periphery, as revealed by stochastic VH gene expression, as a
      result of exposure to environmental antigens. Obviously, the peripheral B-cell
      pool characterized by stochastic VH gene expression is selectively replenished by
      newly generated B cells in bone marrow that preferentially expresses 3'VH genes.
      The V kappa genes are, however, expressed in a non-random manner in the neonatal
      and adult B-lymphocyte repertoire that is probably related to VH and V kappa
      association dynamics and/or positive or negative selection. Interestingly, these
      characteristics of neonatal and adult primary repertoire are noted in both B1 and
      B2 lymphocytes. No remarkable age-related differences are evident for VH and V
      kappa gene expression. In healthy mice, both the mitogen responsive (available)
      and unstimulated (expressed) B-cell repertoire show similar VH gene expression.
      Interestingly, VH gene expression varies in different organs which may reflect,
      or occur as a result of, the specialized function of each organ. For example,
      J558 gene expression is higher in the peripheral LN where B cells continuously
      encounter exogenous antigens. The skewed VH and V kappa gene expression noted in
      immunodeficient and autoimmune lupus-prone mice reflects the impairment of the
      primary antibody repertoire associated with immunodeficiency and autoimmune
      disorders.

PMID- 8739326
TI  - Murine acariasis: I. Pathological and clinical evidence suggesting cutaneous
      allergy and wasting syndrome in BALB/c mouse.
AB  - We describe here a disease related to mite-associated ulcerative dermatitis in
      BALB/c mice, a strain previously classified as resistant to this condition. The
      disease was recognized by pruritic cutaneous pathology and wasting. Pathologic
      studies showed a marked allergic-type inflammation in the skin. The dominant
      histologic feature was extensive mast cell infiltration in cutaneous lesions and
      in lymphoid tissues, associated with a greatly elevated serum IgE concentration.
      The disease was secondary to infestation with an acarian ectoparasite Myocoptes
      musculinus, and seemed to represent an allergic reaction to the parasite-derived
      substances, with an associated wasting syndrome. This condition may be a useful
      experimental model for allergic diseases.

PMID- 8739327
TI  - Effects of polar glycopeptidolipids of Mycobacterium chelonae (pGPL-Mc) on
      haematopoietic regeneration and resistance to infection of sublethally irradiated
      mice.
AB  - The influence of polar glycopeptidolipids of Mycobacterium chelonae (pGPL-Mc)
      treatment on the reversal of irradiation-induced leukopenia (granulocytopenia,
      monocytopenia) and thrombocytopenia and its ability to protect mice against
      lethal infections were investigated in this study. The administration of pGPL-Mc
      to irradiated mice significantly accelerated the recovery of leukocyte and
      thrombocyte numbers in the peripheral blood. Granulocytes and monocytes were the
      principal cells of the leukocyte population that responded to the potent stimulus
      of this product. The reversal of granulocytopenia and monocytopenia in treated
      mice was achieved on day 14 and reached a peak value on day 20. Responses in mice
      receiving 100 mg/kg of pGPL-Mc was about 40-fold compared to controls and about 4
      fold compared to the rhG-CSF-treated group. Normal levels of thrombocytes were
      reached by day 17 in mice treated with 100 mg/kg and by day 20 in those receiving
      25 mg/kg of pGPL-Mc. The administration of pGPL-Mc to mice with irradiation
      induced granulocytopenia was characterized by highly significant protection of
      these animals against lethal Klebsiella pneumoniae or Escherichia coli
      infections. Therefore, pGPL-Mc appears to possess a considerable potential for
      improvement of the outcome of radiotherapy and may contribute to the successful
      avoidance of irradiation-induced toxicities.

PMID- 8739328
TI  - The absence of gut flora, the doses of antigen ingested and aging affect the long
      term peripheral tolerance induced by ovalbumin feeding in mice.
AB  - Several factors have been shown to affect the induction of peripheral tolerance
      induced by the oral route, also called oral tolerance. In the present study, we
      explored factors that shorten the duration of the IgG and IgE antibody
      unresponsiveness induced after ingestion of ovalbumin (OVA). Accordingly, we
      explored the effects of aging, the absence of gut flora, and ingestion of either
      one dose of 20 mg OVA or 5 doses of 1 mg OVA in young adult conventional (CV)
      mice and germ-free (GF) mice, and older CV mice. In young CV mice fed 20 mg OVA,
      IgG and IgE antibody unresponsiveness were still observed 2 to 3 months after
      feeding. In CV mice, neither aging nor 5 low doses of OVA prevented the induction
      of IgG and IgE antibody unresponsiveness but they reduced its duration. In young
      GF mice given 20 mg OVA, IgG antibody unresponsiveness only lasted between 7 and
      21 days after feeding, but IgE antibody unresponsiveness lasted much longer. We
      believe these findings should be taken into account in the treatment of
      autoimmune and allergic diseases, for cases requiring conditions of antigen
      ingestion suitable for lasting suppression of peripheral antibody responses. The
      animal models used here might be of interest for better understanding of the
      mechanisms involved in the long-term persistence of oral tolerance.

PMID- 8739329
TI  - Similar binding properties for a neutralizing anti-tetanus toxoid human
      monoclonal antibody and its bacterially expressed Fab.

PMID- 8739330
TI  - Genetic changes in the origin and development of renal cell carcinoma (RCC).
AB  - 64 kidney tumours of clear cell histopathology were analysed with non-isotopic
      SSCP and HA for the presence of VHL gene defects. All positive cases were further
      characterised by direct sequencing. In 30 tumours (48%) mutations were identified
      in the coding region of the VHL gene. Other tumours were examined for methylation
      changes in 5' CpG islands in exon 1 Bisulphite genomic sequencing which gives
      positive signal for methylated cytosines, was used in this analysis and in 7
      tumours hypermethylation of 5' CpG islands was found. These findings suggest that
      VHL gene mutations together with methylation associated inactivation of the VHL
      gene are important events that predispose to renal cell tumorigenesis.

PMID- 8739331
TI  - Correlations between clinical, electrophysiological and genetic findings in
      hereditary motor and sensory neuropathy type I (HMSN I).
AB  - We evaluated the correlation between clinical signs, electrophysiological data
      and molecular genetics findings in patients with HMSN I. We found a duplication
      in the PMP-22 gene in 60% of HMSN I families. We compared clinical and
      electrophysiological data between 23 patients with duplication and 18 patients
      without duplication. No statistically significant differences in age of onset of
      symptoms, clinical signs and electrophysiological parameters were found.

PMID- 8739332
TI  - I/D polymorphism at the locus for ACE and apo A-I gene promoter polymorphism as
      risk factors for coronary artery disease in patients with familial
      hypercholesterolemia.
AB  - In our study we searched for an association between the insertion/deletion (I/D)
      polymorphism at the ACE locus as well as apo A-I promoter polymorphism and
      coronary artery disease (CAD) in patients with familial hypercholesterolemia
      (FH). 34 FH patients over 40 years were ascertained; 16 patients with CAD were
      compared with 18 patients without CAD. There was an excess of DD or ID genotype
      in FH patients with CAD (OR = 4.9, CI = 1.17-22.17; Fisher exact p = 0.012),
      however, no association between G to A substitution in the promoter region of the
      apo A-I gene and CAD was found. Our results suggest that the DD/ID genotype at
      the ACE gene locus might be an important genetic risk factor for CAD in FH
      patients.

PMID- 8739333
TI  - CTG repeat analysis in lymphocytes, muscles and fibroblasts in patients with
      myotonic dystrophy.
AB  - The mutation responsible for DM has been identified as the amplification of a
      polymorphic (CTG)n repeat in the 3' untranslated region of the myotonin
      proteinase gene. To examine somatic instability of the repeat, we studied tissue
      variability of the CTG expansion of three mesodermally derived tissues:
      lymphocytes, cultured fibroblasts and muscle cells. In six patients with adult
      onset DM, the repeat region was larger in skeletal muscles and fibrolasts as
      compared to lymphocytes. Our findings indicate that somatic CTG instability
      between examined tissues might take place postnatally by a selection mechanism in
      lymphocytes.

PMID- 8739334
TI  - DNA microsatellites in domesticated dogs: application in paternity disputes.
AB  - Microsatellite sequences, like minisatellites, are a class of polymorphic DNA
      fragments that are randomly distributed throughout mammalian genome. Although
      they express significantly lower variation than minisatellites, they have
      potential to be used in paternity disputes. However, the inherently lower
      variability together with the more genetically homogeneous nature of pedigree
      dogs due to the major inbreeding, raised doubts about the effectiveness of
      microsatellites in canine paternity (paternage) testing. Using about 20
      polymorphic canine specific microsatellites on various dog litters demonstrated,
      that canine microsatellites provide a perfectly adequate basis for assigning
      paternity in pedigree breeds. Microsatellite paternity tests are more
      straightforward to perform and interpret than those based on minisatellites (DNA
      fingerprinting) and require as little as 0.1 ml of blood. The case presented here
      was a paternity dispute in labradors, where a mixed paternity was suspected.

PMID- 8739335
TI  - Differential allelic expression of lactoproteins: a model to study
      transcriptional regulation.
AB  - The importance of transcriptional control of gene expression has been documented
      in relation to several genetic defects in man. Mutations in the promoter region
      of genes have been shown to be responsible for defects which are characterized by
      over or under expression of genes. Genetic polymorphisms of the milk protein
      genes, and their high level of tissue specific expression during lactation,
      represent a suitable system for studying regulation of gene expression.
      Quantification of the allele specific protein products has demonstrated unequal
      allelic contribution in the expression of the beta lactoglobulin (beta-LG)
      alleles A and B. The DNA sequence analysis of the beta-LG promoter revealed
      allele specific polymorphisms related to the coding region genotypes.

PMID- 8739336
TI  - Neonatal and placental factors in relation to the mode of umbilical cord
      insertion. Stereological analysis of chorionic villi.
AB  - Neonatal and placental factors and compartment volumes of placental parenchyma in
      relation to variations of cord insertions in normal human placentae were
      examined. The results of our investigation suggest that the mode of umbilical
      cord insertion has no significant effect on examined components. Stated
      differences are probably the effect of biological variations during normal
      placental and fetal development.

PMID- 8739337
TI  - Determination of the femoral and pelvic geometrical parameters that are important
      for the hip joint contact stress: differences between female and male.
AB  - The difference between male and female femoral and pelvic geometry was studied by
      considering some geometrical parameters such as interhip distance, inclination of
      the crista iliaca, diameter of the femoral head and centre-edge angle of Wiberg.
      The values of these parameters were determined for 79 healthy female and 21
      healthy male subjects. Standard anterior-posterior radiographs were used and
      processed by the computer-aided system. The results show some important sex
      differences in femoral and pelvic geometrical parameters which determine the hip
      joint contact stress.

PMID- 8739338
TI  - Astereological analysis of the FRTL-5 cells up to four days after trypsinisation.
AB  - FRTL-5 cells grow as a monolayer culture in vitro and they must be detached from
      the solid surface by trypsin before reseeding. The aim of this study was to
      examine by light microscopy and by the astereological method the changes that
      occur in FRTL-5 cells one, two, three or four days after trypsinisation. The most
      pronounced qualitative and quantitative changes were seen from the first to the
      second day after trypsinisation, as the area of the cells increased by 119%,
      their nuclei by 71% and the cytoplasm by 150%, while the nuclear-cytoplasmic
      ratio decreased by 42%. Significant increases in the average area of the cells,
      their average nuclear diameter and perimeter were seen also on the third and
      fourth days, while the average nuclear-cytoplasmic ratio decreased significantly
      on the first three days after trypsinisation and then remained constant.

PMID- 8739339
TI  - Energy metabolism of fibre types within fascicles of human muscles.
AB  - In human latissimus dorsi muscle a preponderance of type 2b fibres in the first
      fascicle layer and of type 1 fibres in the second layer was found. NADH
      dehydrogenase (NADH) and alpha-glycerophosphate dehydrogenase (GPDH) which were
      measured histophotometrically in type 1, 2a, and 2b fibres showed either extreme
      or only partial overlapping regarding the activity of metabolic enzymes. In
      different fascicle layers the average activity of both enzymes did not differ
      significantly among the fibres of the same type, neither did the NADH and GPDH
      activity of type 2a and 2b.

PMID- 8739340
TI  - Morphometric analysis of fetal rat lung after the administration of Pyralene
      3000.
AB  - The effects of the application of commercial low chlorinated PCB Pyralene-3000 on
      rat lung development during late gestation were studied. In the developing lungs
      (17.5 to 21.5 days) the volume density (Vv) of a particular compartment and
      length density of potential air spaces (Lv) were determined. Significant
      difference (p < 0.01) in epithelium to mesenchyme ratio (Epi/Mes) occurred
      between the control and treated groups on day 20.5 due to an increased volume
      proportion of mesenchyme (Vvmes) in the treated group suggesting a small delay in
      maturation. Decreased volume proportion of potential airspaces (Vvair) was
      observed on days 18.5 and 20.5. However, no differences were found on day 21.5 in
      any variables studied.

PMID- 8739341
TI  - The effect of the combination therapy with sucralfate and famotidine on
      experimentally induced duodenal ulcers in rats.
AB  - The combination of sucralfate (SUC) and famotidine (FAM) at subtherapeutic dose
      on cysteamine-induced duodenal ulcers (3 x 250 mg/kg) in female rats was studied.
      Subtherapeutic doses were determined in the preliminary studies. They were 200
      mg/kg SUC and 0.2 mg/kg FAM (twice a day). The macroscopic examination was done
      24 hours after first application of cysteamine. The effectiveness of SUC and FAM
      combination in subtherapeutic doses was confirmed by decreased number (from 1.3
      to 0.5), length (from 5.5 mm to 1.9 mm), severity of duodenal ulcers (from 3.4 to
      1.2) and reduction of ulcerative index by 54.4%.

PMID- 8739342
TI  - Effects of chloropyramine and famotidine on postischaemic and posthypoxic
      myocardial damage in isolated rat hearts.
AB  - In isolated rat hearts effects of chloropyramine (CP), histamine H1 antagonist,
      and famotidine (FA), H2 antagonist, upon two different myocardial injuries,
      ischaemia-reperfusion and hypoxia-reoxygenation were studied. In both types of
      injury the effects of drugs were seen mainly during reperfusion and
      reoxygenation, respectively. During reperfusion neither CP nor FA influenced
      amplitude of contractions, but CP lowered heart rate, +dp/dtmax and coronary
      flow. During reoxygenation CP and FA lowered early posthypoxic contractions,
      whereas CP decreased and FA increased heart rate. CP and FA did not significantly
      influence the post-ischaemic and posthypoxic lactate dehydrogenase (LDH) release.
      Present results indicate the existence of H1 and H2 receptors in rat heart as
      well as their involvement in both types of studied injuries.

PMID- 8739343
TI  - Mast cell histamine in gastric secretion--a study on the isolated portion of a
      guinea pig stomach.
AB  - The effects of an H3-agonist, R-alpha-methylhistamine (0.1 and 1 microM), on
      gastric acid secretion and on mast cell histamine release was studied on the
      isolated portion of guinea pig stomach. Secretion, induced by calcium ionophore,
      A23187 (1 microM), and by vagal stimulation was determined by continuous pH
      measurement, mast cell degranulation was examined histologically. Secretory
      effects were not significantly changed by H3-agonist. Mast cell degranulation,
      elicited by vagal stimulation, was not influenced by R-alpha-methylhistamine, but
      the degranulating effect of A23187 was clearly augmented by the H3-agonist. The
      results support the view that H3-receptors could influence the release of mast
      cell histamine in the guinea pig stomach.

PMID- 8739345
TI  - Histaminergic drugs as modulators of CNS function.
AB  - The first indication that histamine might be important in the functioning of the
      brain was the finding that the centrally penetrating histamine H1 antagonists had
      marked sedative properties. Subsequently with the development of more specific
      compounds and drugs for the H1, H2 and H3 receptors a greater understanding of
      the neurotransmitter/modulator role of histamine in the CNS has been possible.
      Histamine is now associated with wakefulness, suppression of seizures,
      hypothermia and emesis. The histamine H1 antagonists have been shown to
      potentiate opioid-induced analgesia, and modify eating and drinking patterns as
      well as endocrine secretions from the pituitary gland. Additionally, clinically
      useful antidepressants have been shown to inhibit histamine-sensitive adenylate
      cyclase from the mammalian brain. Recently, a possible role for both histamine H1
      and H2 receptors in schizophrenia has been reported. As more specific and
      centrally-penetrating histaminergic compounds are developed, so the roles of
      histamine as a neurotransmitter/modulator in the brain will be better understood.

PMID- 8739344
TI  - Effects of an anaesthetic on plasma levels of histamine and tele-methylhistamine
      in the cat.
AB  - The effects of intravenous injection of ketamine on plasma levels of histamine
      (Hi) and its metabolite, tele-methylhistamine (MeHi) were studied in the cat. The
      results showed that the anaesthetic, given in doses which prolonged anaesthesia
      in the cat (2.5-7.5 mg/kg) caused Hi release, which raised the concentrations of
      Hi in plasma up to 1600%. It was followed by a slower and also significant
      increase of plasma MeHi levels (up to 1200%). When urethane was used as an
      anaesthetic no changes of plasma levels were noticed. However, about 50% of i.v.
      injections of Ringer-Locke solution were followed by a transient increase of
      plasma Hi and MeHi concentrations.

PMID- 8739346
TI  - TSG-6, a glycoprotein associated with arthritis, and its ligand hyaluronan exert
      opposite effects in a murine model of inflammation.
AB  - TSG-6 is an arthritis-associated hyaluronan binding protein whose production in
      synovial cells, chondrocytes, fibroblasts and mononuclear cells is stimulated by
      TNF-alpha and IL-1. The purpose of this study was to gain insights into the role
      of TSG-6 and its functional interactions with hyaluronan in inflammation. In the
      murine air pouch model of carrageenan/IL-1-induced inflammation TSG-6 showed a
      dramatic inhibitory effect on the cellular infiltration of the inflammatory site
      by neutrophilic PMN, while hyaluronan enhanced cellular infiltration. There was
      no indication of a neutralizing or cooperative effect when TSG-6 and hyaluronan
      were injected together. The potent antiinflammatory effect of TSG-6 along with
      its induction by proinflammatory cytokines suggests that TSG-6 is part of a
      negative feedback loop in the control of the inflammatory response.

PMID- 8739347
TI  - Human interleukin-2 (IL-2) expressed by transfected mammalian cells.
AB  - cDNA for human interleukin-2 (IL-2) was cloned into the pRc/RSV vector for
      expression in animal cells. Baby hamster kidney (BHK-21) cells and Chinese
      hamster ovary (CHO) cells were transfected several times using calcium phosphate
      and electroporation methods with the construct pRc/RSV SIGIL2. Different
      transfection efficiencies were obtained. The biological test on CTLL-2 (mouse
      cytotoxic lymphocytes) showed that the kinetics of cell proliferation were
      different from those of rIL-2 (recombinant IL-2) expressed in bacteria and in BHK
      cells. When high concentrations of rIL-2 were applied, an inhibitory effect on
      CTLL-2 was observed when bacterial product was used, whilst rBHK interleukin
      caused no inhibition. Recombinant BHK IL2 induced a slower response of CTLL-2
      cells at the beginning of the cultivation, however, prolonged activity was
      detected at the later stage of the experiment.

PMID- 8739348
TI  - Treatment of solid tumors should obligatorily be combined with the in vivo
      codepletion of tumor-protecting, CD8+/HLA-DR(+)-suppressor T cells by
      alloreactive donor T cells whose preprogrammed cell death allows a high GvL
      effect before GvHD can be established. Results of animal experiments, including
      more than 6000 mice.
AB  - The FACS-analysis of diseases as different as cancer, autoimmune disorders and
      chronic (retro)viral infections, including HIV-infection, shows -at least
      temporarily- a common feature of lymphocyte hyperactivation, characterized by
      cellular activation markers (HLA-DR, CD26, CD38, CD69, CD2R and/or CD30), as well
      as by solubilized membrane structures, such as beta-2m, sICAM-I, sIL-2R/sCD25,
      sCD8, and by some oversecreted immunocyte products (e.g. neopterin, lysozyme
      and/or cathepsin D). We tested two potential approaches to down-regulate the
      pathologically elevated CD8+ and HLA-DR+ T cells: (a) In animal model, we tested
      the sensibility of these, disease inducing and maintaining T cell subsets to in
      vitro pretreated (cell death preprogrammed) semi-syngeneic and allogeneic donor T
      cells in tumor-bearing mice. (b) In the first clinical study, we used a novel
      combination of FDA-approved drugs which inhibits Ca(2+)-influx and concomitantly
      down-regulates cytosolic cAMP in patient's overstimulated immunocompetent cells.
      We could achieve a 94.6-100% long-term survival in tumor-bearing mice. In
      patients, large primary tumors and large metastases shrinked by 80-85% and small
      metastases disappeared completely. Since in HIV-infected persons, the increased
      number of HLA-DR+ CD38+T (T8) cells is associated with a fall in CD4-level and
      with development of AIDS, we are looking for the elimination of these HLA-DR+
      targets by our novel technique in two AIDS-simulating (FIV/FeLV and SIV) animal
      models.

PMID- 8739349
TI  - Cultivation of mouse-mouse hybridomas producing IgM monoclonal antibodies.
AB  - The mouse-mouse hybridomas producing monoclonal antibodies (MAbs) for ABO blood
      group determination were cultivated for 10 days in 25 cm2 Roux bottles using
      standard cultivation medium (DMEM) with different foetal-calf serum (FCS)
      concentrations (2-13%). The highest specific production rates (200-1100
      micrograms/10(6) cells/day) for MAbs were measured at the end of the cultivation:
      this phenomenon could be explained by advanced cell death and liberating the
      content of the cells into the medium.

PMID- 8739350
TI  - Searching for new TNF-alpha analogs having potential application in cancer
      therapy.
AB  - Two new TNF-alpha analogs were prepared and tested for their anti-tumor activity
      on fibrosarcoma SA-1 tumor model in vivo. In analog LK-801 two histidines
      (His107His108) were introduced into the surface loop thus enabling efficient
      purification by metal-affinity chromatography. This analog showed less side
      effects and can serve as a lead compound to look for other useful mutations.
      Another analog LK-802 was designed by introduction of additional pair of
      mutations (Cys95Cys148) into LK-801 in order to prepare disulfide linked TNF
      trimers. Cytotoxicity on mouse cell line L929 was comparable to TNF-alpha, but
      effect on tumor growth was quite reduced. Pharmacokinetic study revealed that
      serum levels of LK-802 were quite low in comparison to native TNF-alpha. This at
      least partially explains why anti-tumor activity of LK-802 is reduced and also
      illustrates the problems in designing the analogs with desired in vivo biological
      properties.

PMID- 8739351
TI  - Potential therapeutic indications for synthetic desmuramyl MDP analogue (LK-409).
AB  - Synthetic desmuramyl analogues are potentially immunostimulating drugs. Until
      today a lot of different molecules were constructed, some with interesting
      augmenting properties, but most of them with unpleasant pyrogenic side effects.
      LK-409, 7-oxooctanoyl-L-alanyl-D-isoglutamine, synthesised at the Pharmaceutical
      faculty of Ljubljana, is an apyrogenic derivative with promising
      immunostimulating activity. LK-409 and the control substance romurtide were
      tested for more than 50 parameters. All the immune response levels were included
      in the study; the development and proliferation of stem cells from bone marrow,
      the natural defence mechanisms with special regard to the function of phagocytic
      cells, the humoral immune response with special regard to the development of
      plaque forming cells and the cellular immune response with regard to the
      proliferating ability of the immune cells and production of regulating and
      differentiating cytokines, in vitro and in vivo. Results of LK-409 and romurtide
      activity were sorted in six groups, and evaluated. The analysis shows that LK-409
      affects the measured parameters more efficiently than does romurtide. The most
      pronounced effect was stimulation of the immune response in drug and tumor
      induced immunosuppression.

PMID- 8739352
TI  - Thrombin-induced membrane currents in native Xenopus follicles.
AB  - The presence and properties of thrombin receptors have been investigated in
      Xenopus Laevis follicles. In follicles, voltage-clamped at -60 mV or -80 mV, sub
      micromolar concentrations of thrombin (Thr) induce smooth inward currents carried
      by chloride ions, which desensitize over tens of minutes. This desensitization is
      prevented by PKC inhibitors (staurosporine and H7). Responses are inhibited by
      hirudin. Inconsistent responses can be observed in defolliculated oocytes. Thr
      responses, readily recorded in hypo-osmotic solution are abolished by perfusion
      of normal frog "Ringer" or by the addition of 50 mM sucrose. Thus Thr acts on
      receptors present in the follicular cells triggering the opening of chloride
      channels by acting on receptors, likely to be located on follicular cells, via a
      PKC-regulated pathway.

PMID- 8739353
TI  - Morphology and physiology of digestive epithelia in Decapod crustaceans.
AB  - The anatomy and cellular composition of the digestive tract of decapod
      crustaceans is in many aspects considerably different from the vertebrate system.
      These differences include primarily the gastric mill and a sophisticated filter
      apparatus in the stomach and the hepatopancreatic tubule system with its bi
      directional movement of fluids. Further differences are the lack of a strongly
      acidic pH and pepsin in the stomach. Consequently, many of the physiological
      processes are fundamentally different as well, particularly the physical and
      chemical processing of the feed and the synthesis, storage and mode of action of
      the digestive enzymes. The hepatopancreas is a central organ of metabolism and
      includes functions which, in vertebrates, are confined to intestine, liver and
      pancreas.

PMID- 8739354
TI  - Reorganisation of the urothelial luminal plasma membrane in the cyclophosphamide
      treated rats.
AB  - The luminal surface of differentiated urothelium is characterised by the presence
      of asymmetric unit membrane (AUM) which contains four major integral proteins,
      uroplakins. Cyclophosphamide (CP) causes extensive denudation of the urothelium
      that is followed by regeneration. In this study the differentiation of the
      urothelial luminal plasma membrane was examined in CP treated rats by electron
      microscopy. Single dose of cyclophosphamide was injected and rats were killed
      after 1, 3, 7, 14 or 28 days. One day after the treatment only few cells remained
      in the urothelium. They had a flat surface and did not stain with anti-AUM
      antibody. During regeneration cells with short or pleomorphic microvilli and
      latter cells with ropy and leafy microridges appeared. Cells with either type of
      microvilli were not labelled whereas cells with microridges were labelled with
      anti-AUM. At day 28 the luminal surface was normal and labelled. These results
      show a good correlation of morphogenesis and the expression of uroplakins.

PMID- 8739355
TI  - ATP-dependent redistribution of phosphatidylethanolamine in the plasma membrane
      of an epithelial and a hepatocytic cell line.
AB  - The redistribution of spin-labeled phospholipid analogues of sphingomyelin (SM)
      and phosphatidylethanolamine (PE) from the outer to the inner leaflet of the
      plasma membrane of an epithelial (CaCo-2) and a hepatocytic cell line (HepG2) was
      investigated. The amount of analogues in the outer leaflet was determined by
      their back-exchange to bovine serum albumin (BSA). For both cell lines a fast ATP
      dependent inward movement of spinlabeled PE (SL-PE) was found while SL-SM
      redistributed only slowly by a passive mechanism. After depletion of
      intracellular ATP transverse diffusion of SL-PE was similar to that of SL-SM. The
      data are compatible with the presence of an aminophospholipid translocase in both
      cell lines.

PMID- 8739356
TI  - Growth and differentiation of urothelial cells in explant culture.
AB  - Growth and differentiation of urothelial cells in explant cultures of mouse
      urinary bladder were studied by means of scanning and transmission electron
      microscopy and lectin binding analysis. The proliferation and growth of
      epithelial cells over the cut edges of the explant and over the substrate began
      after explant attachment to the substrate was performed. The exogene EGF plays no
      important role in cell proliferation and epithelialization. The urothelial cells
      which are in contact with the stroma of the explants differentiate in a similar
      way as "in vivo". On the contrary, the urothelial cells which grow over the
      substrate exhibit only an epithelial stratification and are differentiated only
      partially.

PMID- 8739357
TI  - The effect of Zn on the digestive gland epithelium of Porcellio scaber (Isopoda,
      Crustacea).
AB  - The effect of zinc (Zn)-contaminated food on the shape of digestive gland
      epithelium was studied in the terrestrial isopod, Porcellio scaber. In animals
      fed with 5,000 micrograms Zn g-1 dry wt. of food, the epithelium was flattened in
      the anterior part of the gland tube. In the posterior part of the gland tube, the
      shape and size of cells did not change drastically, but they had folded apical
      surface. In animals fed with more Zn-contaminated food (10,000 micrograms Zn g-1
      dry wt.) the epithelium was uniformly flattened and the basal lamina was
      intensively folded. In both cases, reduction of lipid bodies was evident. The
      possibility of using the shape of the gland epithelium as a biomarker of toxic
      chemicals is discussed.

PMID- 8739358
TI  - Desquamation of urinary bladder epithelial cells.
AB  - Desquamation of urothelial cells is brought about by various specific inductions.
      Moderate stress in mouse female adults induced by constant illumination for 96
      hours results in desquamation of superficial and intermediate cells. Application
      of endotoxin LPS involves desquamation of single cells as well as whole sheets of
      cells from the underlying lamina propria. Cell detachment involves interruption
      of tight junctions between neighbouring cells, reorganisation of intermediate
      filaments and concentration of different vacuoles or multivesicular bodies. These
      results clearly demonstrate the involvement of specific adhesion mechanisms
      during detachment and desquamation of uroepithelial cells.

PMID- 8739359
TI  - Ultrastructural analysis of the integument during the moult cycle in Ligia
      italica (Crustacea, Isopoda).
AB  - The formation of the cuticle was investigated during moulting of the isopod
      crustacean Ligia italica. The intermoult cuticle is a four-layered lamellar
      structure composed of chitin-protein fibrils and mineralized in its upper half.
      The distribution of calcium carbonate in cuticle during moult cycle was
      determined by cytochemical methods and X-ray microanalysis, Epi-and exocuticle
      are secreted during premoult. Calcium is resorbed from the old cuticle and
      accumulates in the ecdysal gap as calcium granules. Endocuticle is secreted after
      moult when the mineralization of exocuticle starts. The shape and ultrastructure
      of epithelial cells change during cuticle secretion and mineralization.
      Mitochondria, bundles of filaments, calcium granules and large amounts of
      glycogen accumulate in the apical cytoplasm of cells in premoult animals.

PMID- 8739360
TI  - Lipid lateral mobility in the plasma membrane of whole plant cells.
AB  - Fluorescence photobleaching recovery was used to measure the apparent lateral
      diffusion coefficient and mobile fraction of a fluorescent lipid probe in the
      plasma membranes of whole plant cells, i.e., in the presence of cell walls.
      Interfering fluorescence from the cell wall was reduced by extensive washing and
      then subtracted from the recovery recordings. Mobility characteristics of plasma
      membrane lipids in whole cells were found to be very similar to those in
      protoplasts.

PMID- 8739361
TI  - Transverse mobility of aminophospholipids in the plasma membrane of ram sperm
      cells.
AB  - The transbilayer movement of aminophospholipids in the plasma membrane of ram
      sperm cells was investigated using spin-labeled lipid analogues. After
      incorporation, spinlabeled phosphatidylserine (SL-PS) and phosphatidyl
      ethanolamine (SL-PE) rapidly disappeared from the exoplasmic monolayer. Even at
      lower temperatures (10 degrees C) the inward movement of SL-PE is fast. The
      initial velocities of the internalization of SL-PS and SL-PE were compared with
      those of ram and human erythrocytes.

PMID- 8739363
TI  - Diffusion layer caused by local ionic transmembrane fluxes.
AB  - Ionic concentrations in the close proximity of a carrier may be different from
      those in the bulk solution. An immediate layer in the solution in which this
      situation occurs is known as a diffusion layer. Such diffusion layers were
      calculated using general diffusion equations and postulating a membrane to be
      homogeneous in the plane with respect to its permeability. In contrast, the
      present mathematical model considers single-carrier mediated transport of ions
      across the membrane and their diffusion away from the carrier site into the
      electrolyte solution. In particular, the transport of Ca2+ ions is considered.
      The diffusion of electrolyte ions (Na+ and Cl-) and of Ca2+ ions is described by
      the Nernst-Planck electrodiffusion equation. The relation between the local
      electric potential and the ion concentrations is taken into account by the
      Poisson equation. The equations are solved numerically for radial symmetry by the
      relaxation method. The model predicts concentration and potential profiles in
      dependence of the flux rate of Ca2+ ions. It is shown that for fluxes mediated by
      a single carrier, a diffusion layer becomes significant if the flux is larger
      than 10(5) Ca2+ ions per second.

PMID- 8739362
TI  - Deacylation of influenza virus hemagglutinin does not affect the kinetics of low
      pH induced membrane fusion.
AB  - The relevance of palmitoylation of cysteine residues of influenza virus
      hemagglutinin (HA) for the HA-mediated membrane fusion triggered at low pH is
      investigated. Either wild-type HA (subtype H7) or mutant HA devoid of fatty acids
      were expressed in insect cells. The kinetics as well as the extent of fusion of
      HA-expressing cells with human erythrocyte ghosts were measured by a membrane
      mixing assay. Fusion was measured continuously at different pH by fluorescence
      dequenching of the lipid-like fluorophore R18 initially incorporated into the
      erythrocyte membrane. No significant difference between fusion of wild-type and
      mutant HA expressing cells with ghosts could be detected showing that deacylation
      does affect neither the extent nor the kinetics of fusion.

PMID- 8739364
TI  - EPR oximetry: reduction of cell respiration by vinblastine.
AB  - Influence of vinblastine (VLB) on the rate of oxygen uptake by HeLa cells was
      studied using the electron paramagnetic resonance (EPR) method. A suspension of
      cells was labelled with spin probe 15N PDT. Broadening of the EPR spectrum line
      widths in the presence of O2 was used to measure its concentration throughout the
      sample. VLB decreased the rate of O2 consumption, but did not influence the
      viability of cells at the concentration used (1 ng/ml). In addition,
      intracellular O2 concentration was measured using a paramagnetic broadening agent
      CrOX. No significant difference in the intracellular O2 concentration with
      respect to the extracellular was observed neither in VLB treated nor in untreated
      cells.

PMID- 8739365
TI  - MRI mapping of microvascular permeability and tissue blood volume.
AB  - A quick and automated method for quantitative spatial mapping of tissue
      characteristics derived from contrast enhanced MR imaging by a macromolecular
      contrast medium (MMCM) was used in normal rats. Specifically, an established two
      compartment unidirectional flow kinetic model was automatically implemented on a
      pixel by pixel basis to calculate permeability surface area product (PS) and
      tissue fractional blood volume (BV) from MRI dynamic intensity data. The utility
      of PS and BV maps were evaluated in the normal rat abdomen where a range of
      fractional BV was found: from 100% in the vena cava to 1% in skeletal muscles,
      with intermediate values for liver and kidney. Tissue permeability depicted on
      the PS maps was generally low for normal tissues.

PMID- 8739366
TI  - The increase of duration of isometric contraction may not relate to change of
      relative oxygenation of forearm muscle.
AB  - The aim of this study is to ascertain, how an increase in duration of isometric
      contraction influences tissue oxygenation of forearm muscles, undergoing physical
      training. Four subjects underwent 6 weeks of training of the left forearm muscles
      by performing isometric contractions. Subjects repeated 10 s contractions, 10-15
      times in the first, and 20 s contractions in the second 3 week period. Relative
      oxygenation of forearm muscles was measured by using. Near Infrared Spectroscopy
      (CWS2000, NIM Incorporated, Philadelphia). The training increased the duration of
      isometric contraction at 20 kp of experimental forearm muscles by 41 +/- 25 s,
      which was more (P < 0.05) than in control forearm (8 +/- 4 s). This increase was
      not reflected in changes of maximum relative deoxygenation of experimental
      muscles, which decreased by only -6.9 +/- 14.4%. The results show that an
      increase in duration of isometric contraction may not depend on the oxygenation
      of muscle tissue at fixed force of 20 kp.

PMID- 8739367
TI  - Present status of electron paramagnetic resonance (EPR) spectroscopy/imaging for
      free radical detection.
AB  - Our group and others have been working on the development of EPR imaging to
      obtain "in vivo" free radical images. Using a 280 MHz apparatus a pyrrolidine
      nitroxide free radical was localized in the rat abdomen and thorax during its
      kinetic in whole body. We investigated the role of different experimental and
      instrumental parameters on the resolution of the images. The conclusion of these
      studies is that the instrumentation presents the advantage to perform EPR
      measurements on whole body rats with limited sensitivity (50 microM). The present
      resolution (8 mm) allows to get images in which it is not possible to resolve all
      the organs; instead L-band instruments provide images of single organs (up to 25
      mm in size) with a higher resolution.

PMID- 8739368
TI  - Improvement of the method for demonstration of nucleolar organizer regions (NORs)
      in formalin fixed and paraffin embedded tissue using microwave pretreatment.
AB  - For demonstration, accurate evaluation and measurements of nucleolar organizer
      regions (NORs) in nuclei, a good quality reaction of silver staining is required.
      On formalin fixed and paraffin embedded tissue this can be achieved only, if
      special procedures are used. We managed to get sharply delineated, dark brown or
      black dots representing AgNORs (silver stained NORs), that are easy to count and
      measure, with microwave pretreatment of tissue sections before incubation in
      silver solution.

PMID- 8739369
TI  - Combined use of fluorescence microscopy and micromechanical measurement to assess
      cell and membrane properties.
AB  - The combined use of fluorescence microscopy and micromanipulation provides a
      powerful approach for understanding the mechanochemistry of cell membranes.
      Fluorescent labeling of erythrocytes has been used to identify particular
      populations of cells to assess the effects of abnormal deformability on cell
      survival. It was found that cells deprived of surface area are either eliminated
      rapidly from the circulation or undergo a reduction in volume to improve cellular
      deformability. Fluorescence microscopy can also be used to assess the
      distribution of specific membrane components during mechanical deformation and
      fragmentation of cell membranes and so lead to more fundamental understanding of
      the physical association between the membrane bilayer and the underlying membrane
      cytoskeleton.

PMID- 8739370
TI  - Computer support for experiments on isolated hearts.
AB  - The left ventricular pressure (LVP) and ECG signals that appear during and after
      ischaemia tend to be very irregular (fibrillation, arrhythmia). Computer based
      data acquisition system, that we developed to support experiments on isolated
      Langendorff's rat heart, enabled the usage of methods derived from non-linear
      dynamics. To classify the irregularity of heart action, ECG and LVP time series
      have been used to calculate correlation dimension (D2) and largest Lyapunov
      exponent. We compared the results of signals derived from isolated heart at
      standard conditions and hearts rendered ischaemic for 60 minutes. Our results
      show that the level of irregularity can be classified efficiently using the
      quoted approach.

PMID- 8739371
TI  - Stress distribution on the hip joint articular surface during gait.
AB  - The magnitude and the direction of the resultant hip joint force are different in
      different body positions during gait. Therefore the stress distribution in the
      hip joint articular surface also changes. The aim of this work is to study how
      the stress distribution changes if the magnitude and the direction of the hip
      joint force is changed during gait. For this purpose a three-dimensional
      mathematical model is developed. We calculated the values of the peak stress and
      the location of the pole on the articular surface (where the stress is maximal)
      in the successive phases of the walking cycle. The values of the peak stress
      range from 0.8 MPa in the one limb stance phase to 2.6 MPa in the heel strike
      phase.

PMID- 8739372
TI  - Allosteric effects of phenyltrimethylammonium and propidium on
      acetylcholinesterase active site.
AB  - Different spin labelled fluorophosphates and fluorophosphonates with different
      chain length were investigated with respect to their sensitivity to the
      allosteric changes of acetylcholinesterase active site produced by
      phenyltrimethylammonium (Pta) or d-tubocurarine (TC); only fluorophosphates were
      found to be sensitive to these changes. Therefore fluorophosphates were chosen
      also for the study of allosteric effects of propidium. The addition of Pta and
      propidium to spin labelled membrane acetylcholinesterase of the Torpedo marmorata
      electric organ decreased maximal hyperfine splitting of the EPR spectrum,
      indicating that the microgeography of the acetylcholinesterase active site is
      usually changed in a way which increases the freedom of motion of the spin
      label's piperidine ring. TC alone did not change the EPR spectrum, but it
      prevented the influence of Pta and not that of propidium.

PMID- 8739373
TI  - The effect of equinatoxin II on nerve and muscle.
AB  - The effect of equinatoxin II on the excitability of nerve and muscle membrane was
      examined. Neuromuscular transmission was assessed indirectly by measurement of
      isometric muscle contractions. Membrane currents and potentials were measured by
      means of vaseline-gap voltage-clamp and current-clamp methods on single isolated
      skeletal muscle fibres. 10 nM equinatoxin II induces spontaneous twitches of
      skeletal muscle fibres provided that the neuromuscular junction remains intact.
      In curarized muscles and by use of higher final concentrations of equinatoxin II
      prolonged contractures were observed. This may be explained by a pore formation
      in the muscle membrane. An increase in the leakage conductance of skeletal muscle
      fibres supports this hypothesis.

PMID- 8739374
TI  - Mechanoreceptors in insects: Johnston's organ in Nezara viridula (L)
      (Pentatomidae, Heteroptera).
AB  - Behavioural observations of Nezara viridula suggested that the antennae could be
      involved in detecting the substrate vibrations important in intraspecific
      communication of these insects. Therefore the vibrosensitive properties of
      Johnston's organ, a mechanoreceptor sensitive to the movements of the antennal
      flagellum relative to pedicel, were investigated. Vibrational stimuli were
      applied to the proximal flagellar segment where activity in the antennal nerve
      was recorded via a tapered tungsten electrode inserted into the second antennal
      segment where Johnston's organ is located. Sensory cells of Johnston's organ
      scolopidia respond to low frequency substrate vibrations (below 200 Hz). Both
      fast and slowly adapting receptor cells are present. However, the sensitivity of
      Johnston's organ to substrate vibrations in Nezara viridula is much lower than
      that of vibroreceptors in their legs which are known to be involved in
      intraspecific vibrational communication.

PMID- 8739376
TI  - Electromyographic evaluation of experimental nerve grafts suggests better
      recovery with microscope assistance.
AB  - Controversy surrounds the value of optic magnification for peripheral nerve
      surgery. The aim of this study was to compare the loupe magnification with
      microscope-assisted techniques in a rat tibial nerve graft model. The parameters
      studied included motor nerve conduction velocity (MNCV), clinical test equivalent
      (CTE), soleus muscle weight (SMW) and morphometric nerve indices. In the loupe
      and microscope groups MNCV mean was 26.77 +/- 9.37 m/sec and 44.19 +/- 11.36
      m/sec respectively. MNCV results suggest better regeneration in the microscope
      group, as confirmed by CTE, SMW and myelinated fibre (MF) diameter.

PMID- 8739375
TI  - Synaptotagmin II immunoreactivity in normal and botulinum type-A treated mouse
      motor nerve terminals.
AB  - The distribution of synaptotagmin II, a synaptic vesicle protein, was examined by
      immunohistochemistry at normal mouse motor nerve terminals and after botulinum
      type-A treatment. An immunoreactivity to synaptotagmin II was detected in both
      control and botulinum type-A treated motor nerve terminals including newly formed
      sprouts. These data, together with other reports showing the absence of
      synaptotagmin I at the neuromuscular junction, suggest that synaptotagmin II is
      the isoform involved in transmitter release at motor nerve terminals.

PMID- 8739377
TI  - Changes of Schwann cell antigenic profile after peripheral nerve injury.
AB  - Axons and Schwann cells (SC) in the peripheral nerve (PN) are in permanent
      interaction. Both myelin-forming SC (MSC) and nonmyelin-forming SC (NMSC) have a
      defined antigenic phenotype. Four weeks after PN transection, the proliferating
      SC in the distal stump lose some of their antigens, they start to display
      antigenic profile of NMSC and, in addition, to reexpress nerve growth factor
      receptor (NGF-rec) and growth associated protein (GAP-43), two antigens of their
      precursor cells. It can be assumed that migrating SC may differ in their
      antigenic profile in regard to resident proliferated SC in denervated distal
      nerve stump. We found that many SC specific antigens (S-100 protein, glial
      fibrilary acidic protein-GFAP, NGF-rec, GAP-43) are down-regulated in migrating
      SC as compared to SC proliferating in situ in the absence of axons.

PMID- 8739378
TI  - Brainstem auditory evoked potentials and somatosensory evoked potentials in
      prediction of posttraumatic coma in children.
AB  - Follow-up brainstem auditory evoked potential (BAEP) and somatosensory evoked
      potential (SEP) studies were performed within 72 hours after admission in 127
      children with severe head injury (Glasgow Coma Scale score of < or = 8) in order
      to predict quo ad vitam outcome of posttraumatic coma. Outcomes were categorised
      as brain death and survival. On first assessment 50 comatose children had normal
      BAEPs and SEPs. 78% of them survived and 22% deteriorated and died. 45 had
      abnormal findings. 69% of them improved and survived whilst 31% deteriorated and
      died. 32 children did not have recordable BAEPs and SEPs. All of them died. Thus,
      comatose children with normal EP studies have in 78% good prognosis and a bad
      outcome can be reliably predicted.

PMID- 8739379
TI  - Motor evoked potentials during brain surgery.
AB  - In order to obtain a robust method for intraoperative monitoring of motor
      pathways, different stimulation patterns to elicit muscle motor evoked potentials
      (MEPs) were studied during neurosurgical procedures in 3 patients. MEPs were
      recorded by a catheter electrode in the subdural space and/or by needle
      electrodes in limb muscles. For stimulation single pulses and trains consisting
      of two to five pulses were used. Muscle MEPs were only obtained after trains of
      at least 3 stimuli while single/double stimuli were inefficient. Simultaneous
      subdural recordings showed that single and double stimuli only elicited D-waves,
      whereas trains of 3 or more stimuli generated I-waves, as well. We propose that
      train stimulation can overcome the depressive effects of anesthesia on cortical
      motoneurons.

PMID- 8739380
TI  - Mechanically evoked bulbocavernosus reflex and pudendal somatosensory responses
      in children.
AB  - Electrophysiological investigations of sacral functions are unpleasant and as
      such rarely performed in children. A novel approach is presented: bulbocavernosus
      reflex and pudendal cortical somatosensory evoked potentials were studied on
      mechanical stimulation of the penis and compared with their electrically evoked
      counterparts in 21 (5-14 years old) boys. An electromechanical hammer was used
      and only surface electrodes applied. Children preferred mechanical stimulation
      which also evoked reliable responses in more boys. Reflex responses on mechanical
      stimulation were found to be of longer latency, however no latency differences
      between cortical evoked responses to either stimulation were found. We suggest
      the use of mechanical stimulation in uroneurophysiological testing of children.

PMID- 8739381
TI  - 3,4-Diaminopyridine, an orphan drug, in the symptomatic treatment of Lambert
      Eaton myasthenic syndrome.
AB  - The Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disease of
      peripheral cholinergic transmission that results in muscle weakness and autonomic
      dysfunction, due to impaired acetylcholine release. A review of available
      clinical information indicates that 3,4-diaminopyridine (3,4-DAP) used either
      alone or in conjunction with other therapies was effective in treating the motor
      and the autonomic deficits in patients with primary and paraneoplastic LEMS of
      varying degrees of severity. A survey of the medical literature indicates that
      about 150 patients have been treated worldwide with 3,4-DAP. The general view is
      that 3,4-DAP is well tolerated in short- or long-term treatments, with only mild
      side effects. 3,4-DAP is an orphan drug approved for clinical use in many
      european countries that lacks adoptive parents because its exploitation is not
      profitable.

PMID- 8739382
TI  - Upregulation of calcitonin gene-related peptide at mouse motor nerve terminals
      poisoned with botulinum type-A toxin.
AB  - Calcitonin gene-related peptide (CGRP)-like immunoreactivity of motor nerve
      terminals was investigated at different times after local in vivo injection of
      botulinum type-A toxin (BoNT/A) close to the mouse levator auris longus muscle.
      CGRP expression in most of control nerve terminals was undetectable, but markedly
      increased during muscle paralysis and synaptic remodelling and, declined once
      functional recovery occurred.

PMID- 8739383
TI  - Do visual neurophysiological tests reflect magnocellular deficit in dyslexic
      children?
AB  - To address the question of a possible magnocellular visual deficit in children
      with reading problems (dyslexia), we examined pattern ERG and VEP responses to
      stimulation with checks of 24', 49' and 180' in size and of 5%, 42% and 100%
      contrast level. Neurophysiological difference between children with reading
      problems and those without them was found confined to VEP which showed a
      significant prolongation of P100 wave in dyslexic children at highest contrast
      (100%) and smallest checks (24'). Pattern ERG was normal. These results support
      the assumption of a visual deficit in dyslexic children. However, they are not
      consistent with an isolated deficit of the magnocellular function, which,
      theoretically, would cause VEP changes to lower contrast and largest check
      stimuli.

PMID- 8739384
TI  - Can somatosensory system generate frequency following response?
AB  - The aim of this study was to establish whether functional characteristics of the
      somatosensory system structures in man comply with the frequency following
      response (FFR) generators. Somatosensory cerebral evoked potentials (SsCEP) were
      recorded by skin electrodes, and spinal somatosensory evoked potentials (SpEP)
      both by epidural and skin electrodes. In SpEP and SsCEP to trains of electrical
      or mechanical stimuli, a decrease of the amplitude to subsequent stimuli was
      found. SpEP were also attenuated by higher stimulation rates. It is highly
      improbable, therefore, that somatosensory system can contribute to the FFR-like
      response recorded in profoundly deaf people.

PMID- 8739385
TI  - Hypersomnia in association with dysthymia in comparison with idiopathic
      hypersomnia and normal controls.
AB  - Polysomnographic studies in hypersomniac patients with mood disorders are rare.
      Previous studies investigated patients with a severe mood disorder, but our study
      was done in patients with dysthymia, who complained of sleepiness. Mean sleep
      latency test (MSLT) and continuous polysomnographic recording (CPR) were done in
      12 dysthymic patients, in comparison with 12 idiopathic hypersomnia patients, and
      12 normal controls. In dysthymic patients mean sleep latency on the MSLT (13 +/-
      1) was normal, and when CPR was done during 24 hours, no hypersomnia was found
      (553 +/- 24). Dysthymic patients showed an abnormal macrostructure of sleep
      (characterised by an excess of sleep stage I and a decrease of stages 3 and 4),
      which could be related to their complaint of hypersomnia.

PMID- 8739386
TI  - Influence of sympathetic activity, temperature, ischemia and diazepam on thermal
      and vibration thresholds.
AB  - In healthy volunteers thermal specific, thermal pain and vibration thresholds
      were assessed and correlated to each other and to sympathetic nervous system
      parameters. Additionally, different factors such as temperature, diazepam and
      ischemia affecting perception thresholds were evaluated. The thresholds assessed
      did not correlate significantly to each other and to sympathetic skin response
      latency or amplitude. Diazepam influenced the thermal specific, thermal pain and
      vibration thresholds assessed. The preingestion and postingestion (after 30, 60
      and 90 minutes) thresholds did not differ significantly, meanwhile the scatter of
      thermal and vibration thresholds increased obviously. The skin temperature within
      the range of naturally occurring values of control subjects in a state of
      "thermal comfort" affected neither the warm-cold difference limen nor the heat
      and cold pain thresholds. Considerable temperature changes (the warming for 5
      degrees C and cooling for 10 degrees C) influenced the vibration thresholds
      measured. Warming increased and cooling decreased the values recorded. Tourniquet
      induced ischemia influenced only the vibration disappearance thresholds.
      Vibration perception and vibration thresholds varied but differences were not
      significant.

PMID- 8739387
TI  - Assessment of liver regeneration by quantitative MRI analysis.
AB  - Liver regeneration after an extensive liver resection is a serious clinical
      problem, which is difficult to study in detail on patients. Therefore animal
      models were developed to study liver regeneration. Anabolic processes in the
      liver were assessed by measurements of the cholinesterase synthesis, and the
      regeneration of liver mass was monitored by use of magnetic resonance imaging. It
      has been shown that the liver mass reaches 90% of the control within the first
      week after the resection of 75% of the liver. This is partly due to the
      regeneration, and partly to the increased water content of the regenerated liver,
      shown by the magnetic resonance images. The results allow the conclusion that the
      magnetic resonance imaging is a reliable method to assess liver regeneration in
      vivo.

PMID- 8739388
TI  - Application of the nonradioactive in situ hybridization for the localization of
      acetylcholinesterase mRNA in the central nervous system of the rat; comparison to
      the radioactive technique.
AB  - In this preliminary report nonradioactive digoxigenine-based and radioactive in
      situ hybridization procedures for the localization of acetylcholinesterase mRNA
      were tested and compared in rat brain. General patterns of Ache mRNA localization
      observed by both techniques did not differ significantly and were practically the
      same as reported in previous in situ studies on the mammalian brain. Shorter
      procedure time and avoidance of precautions necessary at work with radioactive
      materials are major advantages of nonradioactive technique. Under- and over-
      staining can be prevented by direct examination of coloring reaction. Faint
      staining in the control experiment with heterologous DNA suggests that proper
      stringency is essential for the specificity of staining.

PMID- 8739389
TI  - Molecular basis of signal recognition in olfaction.

PMID- 8739390
TI  - Learned olfactory discrimination of amino acids and their binary mixtures in
      bullhead catfish (Ameiurus nebulosus).
AB  - The question of whether bullhead catfish can discriminate binary mixtures of
      amino acids from the individual components of the mixture was investigated. Two
      groups of catfish were conditioned to different binary mixtures of L-norvaline
      (NVAL) and L-leucine (LEU). The concentrations of the amino acids in the
      conditioned mixtures were adjusted so that in different mixtures either NVAL or
      LEU was the more stimulatory component. Bullhead catfish were unable to
      discriminate the more stimulatory components, but were able to discriminate the
      less stimulatory components and other amino acids from the conditioned mixtures.
      The third group of bullhead catfish was conditioned to L-proline (PRO) and the
      responses to different mixtures of PRO and NVAL were subsequently evaluated.
      Behavioral and electrophysiological (EOG) experiments indicated that the
      difference in relative stimulatory effectiveness levels between NVAL and PRO is >
      30,000 times. For subsequent tests, the concentrations of PRO and NVAL were
      adjusted to form binary mixtures in which PRO and NVAL, respectively, were the
      more stimulatory components. Bullhead catfish conditioned to PRO discriminated
      the mixture if NVAL was the more stimulatory component, but did not discriminate
      PRO from the mixture if PRO was the more stimulatory component. These results
      suggest that binary mixtures of amino acids are initially perceived as the more
      stimulatory components of the mixture.

PMID- 8739392
TI  - Influence of equinatoxin II on coronary smooth muscle membrane fluidity.
AB  - Equinatoxin II forms pores in artificial as well as in natural phospholipid
      bylayers. As it also reduces the perfusion through the coronary arteries it
      seemed reasonable to investigate the interaction of this protein with the
      plasmalemma of the vascular smooth muscle cells more directly with the patch
      clamp method and with EPR using the spin probe methyl ester of 5-doxylpalmitate.
      In the EPR spectra at least three regions in the membranes were identified with
      different membrane fluidity. Application of 0.1 microM or 1 microM equinatoxin II
      increases the portion with the lower membrane fluidity, and irreversibly
      increases the unspecific membrane conductance. This is compatible with the view
      that equinatoxin II forms pores in the membrane bilayer.

PMID- 8739391
TI  - Pseudozoanthoxantin-like compound from Parazoanthus axinellae Adriaticus inhibits
      acetylcholinesterase.
AB  - Acetylcholinesterase is an enzyme responsible for the timely termination of
      acetylcholine action at muscarinic and nicotinic receptors, so it is essential
      for the normal function of cholinergic synapses. Naturally occurring
      acetylcholinesterase inhibitors are relatively rare, but several synthetic
      acetylcholinesterase inhibitors have been developed as potent remedies,
      pesticides, and neurotoxins. Here we describe the inhibition of soluble and
      membrane-bound cholinesterases with a recently isolated and purified
      acetylcholinesterase inhibitor isolated from the crust coral Parazoanthus
      axinellae Adriaticus. This substance with a novel chemical structure might serve
      as a new prototype of cholinesterase inhibitors.

PMID- 8739393
TI  - Life Sciences 1995. Proceedings and abstracts of an international meeting. Gzod
      Martuljek, Slovenia, 23-28 September 1995.

PMID- 8739394
TI  - Of mind and matter--or what really matters in Alzheimer's disease?
      Neurobiological substrates of clinical deficits in Alzheimer's disease.

PMID- 8739395
TI  - The molecular significance of amyloid beta-peptide for Alzheimer's disease.
AB  - Alzheimer's disease is the most common form of dementia. Although the majority of
      the cases occur sporadically, in some rare cases Alzheimer's disease is
      genetically inherited. Pathologically, Alzheimer's disease is characterized by
      the accumulation of senile plaques with-in the extracellular space of brain
      regions known to be important for intellectual functions. In addition to senile
      plaques, deposits of identical biochemical composition are found in the walls of
      meningeal and cerebral blood vessels. Senile plaques are surrounded by
      degenerating neurons indicating a toxic interference of amyloid plaques with
      neurons. The major component of senile plaques is the 4kDa amyloid beta-peptide.
      This peptide has been shown to exhibit neurotoxic properties when added to
      cultured neurons, or injected into rat brains. Amyloid beta-peptide is derived
      from a high molecular weight precursor, the beta-amyloid precursor protein, by
      proteolytic processing. Mutations responsible for the early onset of Alzheimer's
      disease in some families are found within the gene coding for the beta-amyloid
      precursor protein. These mutations strongly influence the generation of amyloid
      beta-peptide resulting in a significant overproduction of the peptide or the
      generation of elongated forms which are known to aggregate and precipitate much
      faster. Moreover, mutations found in other genes known to cause early onset of
      Alzheimer's disease have been shown to interfere directly with the production or
      precipitation of amyloid beta-peptide.

PMID- 8739396
TI  - Inflammatory mechanisms in Alzheimer's disease.
AB  - In recent years many studies have indicated an involvement of inflammatory
      mechanisms in Alzheimer's disease (AD). Acute-phase proteins such as alpha 1
      antichymotrypsin and c-reactive protein, elements of the complement system, and
      activated microglial and astroglial cells are consistently found in brains of AD
      patients. Most importantly, also cytokines such as interleukin-6 (IL-6) have been
      detected in the cortices of AD patients, indicating a local activation of
      components of the unspecific inflammatory system. Up to now it has remained
      unclear whether inflammatory mechanisms represent a primary event or only an
      unspecific reaction to brain tissue damage. Therefore, we investigated whether IL
      6 immunoreactivity could be found in plaques prior to the onset of neuritic
      changes, or whether the presence of this cytokine is restricted to later stages
      of plaque pathology. We confirmed our previous observation that IL-6 is
      detectable in a significant proportion of plaques in the brains of demented
      patients. In AD patients IL-6 was found in diffuse plaques in a significant
      higher ratio as would have been expected from a random distribution of IL-6 among
      all plaque types. This observation suggests that IL-6 may precede neuritic
      changes, and that immunological mechanism may be involved both in the
      transformation from diffuse to neuritic plaques in AD and in the development of
      dementia.

PMID- 8739397
TI  - Decreased phospholipase A2 activity in the brain and in platelets of patients
      with Alzheimer's disease.
AB  - Phospholipase A2 (PLA2) is a key enzyme in the metabolism of membrane
      phospholipids. PLA2 influences the processing and secretion of the amyloid
      precursor protein, which give rise to the beta-amyloid peptide, the major
      component of the amyloid plaque in Alzheimer's disease (AD). We investigated the
      PLA2 activity in two samples: in post-mortem brains from 23 patients with AD and
      20 non-demented elderly controls, and platelets from 16 patients with a diagnosis
      of probable AD, 13 healthy controls and 14 elderly patients with a major
      depression. In AD brains PLA2 activity was significantly decreased in the
      parietal, and to a lesser degree in the frontal, cortex. Lower PLA2 activity
      correlated significantly with an earlier onset of the disease, an earlier age at
      death and higher counts of neurofibrillary tangles and senile plaques. In
      platelets PLA2 activity was also significantly reduced in the AD group as
      compared with healthy and depressed controls. The reduction of the enzyme
      activity in platelets correlated with an early disease onset and with the
      severity of cognitive impairment, indicating a relationship between abnormally
      low PLA2 activity and a more severe form of the illness. The present results
      provide new evidence for a disordered phospholipid metabolism in AD brains and
      suggest that reduced PLA2 activity may contribute to the production of
      amyloidogenic peptides in the disease. Further studies are needed to examine
      whether PLA2 activity in platelets may be useful as a peripheral marker for a
      subgroup of patients with AD.

PMID- 8739398
TI  - The relationship between clinical dementia and neuropathological staging (Braak)
      in a very elderly community sample.
AB  - The neuropathological staging model proposed by Braak and Braak (1991) implies
      that the evolution of neurofibrillary pathology follows a predictable sequence
      and can be ordered in a regular regional hierarchy. A total of 42 cases of an
      elderly population sample, which had been prospectively clinically assessed, were
      examined. Clinical diagnosis was made according to the CAMDEX criteria, and the
      sample reported here did not include cases were vascular dementia according to
      the criteria proposed by Chui et al. (1991). The neuropathological staging
      procedure was applied as originally proposed by Braak and Braak (1991). In
      addition, in all cortical laminae and regions which are essential for the staging
      model neurofibrillary tangles were quantified. Demented cases had significantly
      more areas involved and more advanced neuropathological stages. Cases with stages
      1-3 tended to be non-demented, and cases with stages 4-6 tended to be demented.
      However, there was a considerable degree of overlap and no clear-cut threshold
      could be established. This brings into question the diagnostic value of the
      staging model.

PMID- 8739400
TI  - Diagnostic validity of basic symptoms.
AB  - Although the Bonn Scale for the Assessment of Basic Symptoms (BSABS) [13] has
      come into use in several European countries, its diagnostic validity has not yet
      been sufficiently examined. That is why we have assessed BSABS items on a sample
      of 243 consecutive admissions to the Department of Psychiatry at the RWTH
      University, Aachen, and 79 psychologically healthy persons. Then, a cluster
      analysis was calculated to identify the empirical item-grouping. Five well
      interpretable BSABS subsyndromes were found. In addition, uni- and multivariate
      analyses were computed to evaluate the diagnostic validity of these subsyndromes.
      We were able to show that every BSABS subsyndrome separates at least
      schizophrenic, organic mental and affective disorders from personality, neurotic
      and substance-induced disorders, as well as from psychological health.
      Furthermore, the subsyndrome "information processing disturbances" differentiates
      between schizophrenic and organic mental disorders, on the one hand, and
      affective disorders, on the other, and additionally, the subsyndrome
      "interpersonal irritation" between schizophrenics and all other persons examined.

PMID- 8739399
TI  - Correlations between mental state and quantitative neuropathology in the Vienna
      Longitudinal Study on Dementia.
AB  - Quantitative clinicopathological correlation studies are one way to address the
      question of the relevance of morphological abnormalities in Alzheimer's dementia
      (AD). This paper summarizes results of the Vienna Longitudinal Study on Dementia
      obtained during the past few years and presents a critical discussion on the
      relevance of clinicopathological correlation studies for the pathogenesis of AD.
      Plotting of psychometric test scores against the numbers of plaques, tangles and
      neuropil threads in various cortical areas shows that significant correlations
      are due primarily to very high lesion counts in severely demented patients. These
      data indicate that neocortical neurofibrillary pathology can be considered an end
      stage marker in the pathology of AD. On the other hand, the topographical staging
      of neuritic Alzheimer changes proposed by Braak and Braak (1991) appears to be a
      better reflection of the progression of the degenerative process than numerical
      lesion counts; there is a linear correlation between the Braak stages and Mini
      Mental State scores in 122 aged individuals. Significant correlations are further
      obtained between the severity of dementia and the levels of a number of synaptic
      proteins including synaptophysin and the chromogranins. Taken together, our data
      suggest that none of the classical AD lesions, plaques and tangles, play a
      central role in the pathogenesis of dementia, a fact that is supported by a
      molecular biological study showing that there is no close relationship between
      these lesions and the neurons undergoing degeneration in AD. Whereas neuritic
      pathology is a useful histopathological marker for the diagnosis and staging of
      AD, the major correlate of cognitive deficits is the loss of corticocortical and
      subcorticocortical connections reflected by a depletion of synapses. This
      pathology may be induced by a mismetabolism of the beta-amyloid precursor
      proteins or their interaction with cytoskeletal proteins related to neuronal
      degeneration.

PMID- 8739401
TI  - The ictal electroencephalogram as a marker for the efficacy of electroconvulsive
      therapy.
AB  - The question of how to define a therapeutically adequate electroconvulsive
      therapy (ECT) has been under discussion since the early days of ECT. Although
      convention has asserted a demand for minimum seizure times, the complex
      electrophysiological conditions involved in developing a generalized seizure make
      it problematic for therapeutic efficacy of ECT to be linked only with seizure
      duration. Within the framework of an open clinical study of 40 patients, selected
      parameters of the ictal electroencephalogram (EEG) have now been examined with
      respect to differentiation between therapeutically effective and ineffective
      treatments. For this purpose a rating scale covering both quantitative and
      qualitative features of the ictal EEG was used. Although this study recorded no
      correlations between seizure duration and clinical improvement, correlations were
      established between clinical improvement, on the one hand, and the frequency of
      epileptic discharges and their slowing during the spike-wave phase as well as the
      stereotypy of the discharge or a "stable" pattern of rhythmic spike-wave or sharp
      wave complexes, on the other. The results suggest that several of these EEG
      parameters might be combined to form a marker for therapeutically adequate ECT,
      and that treatment might be controlled accordingly.

PMID- 8739403
TI  - Neurological and medico-social problems of spina bifida patients in adolescence
      and adulthood.
AB  - Chronological changes in the neurological manifestations of spina bifida are well
      recognized in the early developmental periods: fetal, neonatal, infantile, pre
      school and school life. However, little has been written about the medical and
      medico-social problems of spina bifida patients in adulthood. Patients now in
      this age group had the condition diagnosed and managed in an era when modern
      neurosurgical concepts were only just beginning to be established with the aid of
      invasive methodology. In our series of 141 cases of spina bifida, 18 patients
      (13.5%) were over 16 years of age. These included 9 cases each of spina bifida
      aperta (myeloschisis) and spina bifida occulta (spinal lipoma). The ages ranged
      from 16 to 47 years (mean: 23.5 years) in the former and from 16 to 57 years
      (mean: 29.2 years) in the latter group. During the long-term follow-up with
      quantitative analysis of the spinal neurological changes using the spina bifida
      neurological scale (SBNS), the final outcomes appeared very grave. Except for 1
      case in each group-1 grade III in the spina bifida aperta group and 1 grade II in
      the spina bifida occulta group-all patients over the age of 27 years were classed
      as having grade IV disease. There were 2 patients with spina bifida aperta in
      whom postoperative paraplegia appeared after delayed radical repair (at the ages
      of 3 years and 18 years) and 3 patients with spina bifida occulta in whom obvious
      neurological deterioration was observed as the natural history with ongoing
      paraparesis at the spinal level or late onset of sexual problems. The other group
      included 2 patients with spinal lipoma in whom late neurological deterioration
      was observed and who were obliged to undergo a second operation in spite of
      aggressive early procedures performed during infancy. Among the patients with
      spina bifida aperta, 2 had marked ventriculomegaly as a form of long-standing
      overt ventriculomegaly in the adult (LOVA). After the CSF shunt procedure both
      these patients had problems with delicate shunt dependence and requested fine
      shunt flow regulation. Two patients in this group also suffered from severe
      depression. This study involves a limited number of patients, but it may be
      useful for reference on various points: (1) future prospects for the management
      of pediatric cases of spina bifida as practiced in the majority of hospitals; (2)
      natural histories of untreated cases and surgical indications for preventive
      procedure in spinal lipoma in early infancy; and (3) internationally differing
      levels of management of spina bifida and the historical development of individual
      countries' approaches to the problems.

PMID- 8739402
TI  - Facial affect recognition in the course of schizophrenia.
AB  - Deficits in facial affect recognition have been shown repeatedly in
      schizophrenia. However, the stability of this deficit over time remains to be
      clarified. A total of 36 remitted, 32 acutely ill schizophrenic patients and 21
      healthy volunteers participated in a cross-sectional and longitudinal study. All
      subjects were assessed twice within 4 weeks (acute schizophrenics and normal
      controls), or 12 weeks, respectively (remitted schizophrenics). Subjects had to
      identify six basic emotions from corresponding facial expressions shown as
      photographs on a video screen. Both acute and remitted schizophrenics
      demonstrated a stable deficit over time in facial affect recognition unrelated to
      psychopathology and medication. This suggests that deficits in facial affect
      recognition in schizophrenia reflect a trait-like, rather than a state-dependent,
      characteristic.

PMID- 8739404
TI  - Autosomal recessive hydrocephalus with aqueductal stenosis.
AB  - We report the case histories of three sisters with congenital hydrocephalus
      associated with stenosis of the cerebral aqueduct. The parents were a young
      consanguineous couple. In two cases hydrocephalus was detected before birth by
      ultrasonography. We consider these three cases to be of the rare autosomal form
      of hereditary hydrocephalus.

PMID- 8739405
TI  - Morphometric evaluation of the hydrocephalic brain: relationships with cognitive
      development.
AB  - The effects of early hydrocephalus and related brain anomalies on cognitive
      skills are not well understood. In this study, magnetic resonance scans were
      obtained from 99 children aged from 6 to 13 years with either shunted
      hydrocephalus (n = 42) or arrested (unshunted) hydrocephalus (n = 19), from
      patient controls with no hydrocephalus (n = 23), and from normal, nonpatient
      controls (n = 15). Lateral ventricle volumes and area measurements of the
      internal capsules and centra semiovale in both hemispheres were obtained from
      these scans, along with area measurements of the corpus callosum. Results
      revealed reductions in the size of the corpus callosum in the shunted
      hydrocephalus group. In addition, lateral ventricle volumes were larger and
      internal capsule areas were smaller in both hemispheres in children with shunted
      and arrested hydrocephalus. The centra semiovale measurements did not
      differentiate the groups. Correlating these measurements with concurrent
      assessments of verbal and nonverbal cognitive skills, motor abilities, and
      executive functions revealed robust relationships only between the area of the
      corpus callosum and nonverbal cognitive skills and motor abilities. These results
      support the theory of a prominent role for the corpus callosum defects
      characteristic of many children with shunted hydrocephalus in the spatial
      cognition deficits commonly observed in these children.

PMID- 8739406
TI  - Relationship between anterior fontanelle pressure measurements and clinical signs
      in infantile hydrocephalus.
AB  - The treatment of choice in progressive hydrocephalus is drainage of cerebrospinal
      fluid in order to reduce elevated intracranial pressure (ICP). Defining the right
      moment for surgical intervention, however, in a hydrocephalic infant on the basis
      of clinical signs alone can be a difficult task. Clinical signs of raised ICP are
      known to be unreliable and sometimes even misleading. In the present study, the
      relationship between long-term anterior fontanelle pressure (AFP) measurements
      and clinical signs was investigated in 37 infants with hydrocephalus. The
      decision as to whether to operate or not was based on clinical signs alone; AFP
      values were not taken into account. There was an overall difference between the
      non-operated group and the preoperative measurements in the operated group, and
      also between the preoperative and the postoperative measurements in the latter,
      in regard to both AFP measurements and clinical signs. Almost all preoperative
      AFP values were increased. The direct correlation (phi) between most individual
      clinical signs and AFP levels, however, was low (phi = 0.15-0.41). The clinical
      sign "tense fontanelle" showed the best correlation with the AFP levels (phi =
      0.75). Furthermore, using logistic regression analysis, no combination of
      clinical signs could be found which reliably predicted the AFP. The relationship
      between the AFP pressure variables and clinical signs was also examined. The
      pathological A-waves occurred only in the presence of raised (baseline) AFP, a
      situation in which considerably more frequent B-waves were observed as well. It
      was concluded that clinical signs of raised ICP in infantile hydrocephalus are
      not very reliable and AFP monitoring can therefore provide valuable information
      on intracranial dynamics in patients with dubious neurological manifestations of
      progressive hydrocephalus.

PMID- 8739407
TI  - Spinal cord compression resulting from Burkitt's lymphoma in children.
AB  - We report seven cases of spinal cord compression resulting from Burkitt lymphoma
      in boys aged 15 years and below. This became manifest clinically as acute or
      rapidly progressive spinal cord compression. All the patients showed total
      paraplegia with a sensory loss at thoracic level and sphincter disturbances. Four
      patients were operated on, the operation permitting exeresis of an epidural
      tumor. In three cases surgery was followed by chemotherapy. One patient was
      treated exclusively with chemotherapy. Owing to the effectiveness of
      chemotherapy, surgery should be considered only in cases of rapid deterioration
      or for diagnostic purposes.

PMID- 8739409
TI  - Cranial fasciitis of the orbit and maxilla: extensive resection and
      reconstruction.
AB  - A case of cranial fasciitis of childhood is described. This extensive cranio
      orbital-facial lesion in a 3-month-old baby necessitated radical resection and
      immediate orbital and anterior cranial fossa reconstruction. The particular
      requirements of reconstruction in the infant are emphasised.

PMID- 8739408
TI  - Neurophysiological methods testing the psychoneural basis of attention deficit
      hyperactivity disorder.
AB  - Theories concerning the etiology of attention deficit hyperactivity disorder have
      evolved from the 1950s, when it was believed that an injury to or dysfunction of
      the diencephalon was the cause of the syndrome, to the present day, when delayed
      brain maturation is postulated as an explanation. Delay in laying down myelin can
      be investigated by newly developed techniques like computerized EEG and
      transcranial magnetic stimulation. In this study, a group of 15 children 3-7
      years of age suffering from attention deficit were investigated using both
      methods in combination and were compared to a control group of 23 age-matched
      normal children. On the computerized EEG spectral analysis significant
      differences to the control group were found in areas O1 and O2 (P < 0.05,
      Student's t-test). With transcranial magnetic stimulation, the overall difference
      in right/left stimulation was statistically significant (P < 0.001). The results
      suggest delayed myelination at the brain stem reticular formation where the alpha
      rhythm is activated and at the corticospinal pathway as parts of a widespread
      involvement.

PMID- 8739410
TI  - Peritoneo-vulvar catheter extrusion after shunt operation.
AB  - We report an unusual case of catheter extrusion through the external genitalia.
      between the labium majus and the labium minus, in a 6-month-old hydrocephalic
      baby. The event occurred 5 months after placement of a ventriculoperitoneal
      shunt.

PMID- 8739411
TI  - Lymphangiolipoma of the thoracic spine in a pediatric patient with Proteus
      syndrome.
AB  - Proteus syndrome is a rare hamartomatous disorder involving macrodactyly,
      hemihypertrophy, and subcutaneous lymphangiomas; fewer than 25 cases have been
      reported worldwide. We report a case of a thoracic epidural lymphangiolipoma in a
      5-year-old boy with Proteus syndrome. Computerized axial tomography (CT) of the
      thoracic spine revealed a left posterior mediastinal mass that extended into the
      spinal canal through adjacent neural foramina. No sign of spinal cord compression
      was observed despite the extensive volume of tumor within the spinal canal.
      Surgical debulking utilizing a T3-10 laminectomy resulted in gross total
      resection of the tumor. Microscopic examination of the surgical specimen revealed
      a lymphangiolipoma. No previous report of spinal cord involvement has been
      reported in this syndrome. A detailed discussion of the phenotypic features and
      probable mode of genetic transmission is included.

PMID- 8739412
TI  - Infection, the gut and the development of the multiple organ dysfunction
      syndrome.
AB  - It has been hypothesised that failure of the gut is an important
      pathophysiological phenomenon of the generalised inflammatory response that leads
      to the multiple organ dysfunction syndrome (MODS). Abnormal colonisation,
      infections of gut origin, bacterial translocation are all signs of gut failure
      that have been implicated in the pathogenesis of MODS. We have concluded after
      summarising published experimental and clinical studies that have tried to
      correlate the occurrence or prevention (by selective decontamination of the
      digestive tract) of these phenomena with the development of MODS, it seems that
      in some patients it is clear that loss of intestinal barrier function or the
      onset of infection precedes the development of MODS. In other patients, however,
      this relationship is not so clear and it seems that these phenomena may reflect a
      failure of the host's immune and mechanical defence systems and are epiphenoma of
      critical illness. The causal relation between those phenomena and the development
      of MODS are complex and need further clarification.

PMID- 8739413
TI  - Primary non-functioning tumours of the adrenal cortex: an eight-year experience
      in Turkey.
AB  - OBJECTIVE: To report our eight year experience of the treatment of primary non
      functioning adrenal tumours diagnosed incidentally by computed tomography or
      ultrasonography. DESIGN: Open study. SETTING: University hospital, Turkey.
      SUBJECTS: 20 patients with primary non-functioning adrenal tumours that were
      diagnosed incidentally during the eight years 1986-93 and who were treated in our
      department. INTERVENTIONS: All patients underwent detailed endocrine studies
      followed by unilateral adrenalectomy. MAIN OUTCOME MEASURES: Morbidity,
      mortality, and outcome. RESULTS: There were 18 women and 2 men, mean age 50
      (range 24-67). No patient died and one developed a wound infection.
      Histopathological examination showed adrenocortical adenoma (n = 17), carcinoma
      (n = 2, one of which was a 57-year-old woman with a 35 mm tumour), and
      hyperplasia (n = 1). CONCLUSION: Excision of non-functioning adrenal tumours is
      safe and we recommend it because there are no exclusion criteria for malignancy,
      and non-operative treatment has not been clearly defined.

PMID- 8739414
TI  - Frequency of repeated vascular surgery. A survey of 7616 surgical and
      endovascular Finnvasc procedures. Finnvasc Study Group.
AB  - OBJECTIVE: To assess the incidence of repeated vascular surgical operations.
      DESIGN: A population-based cross-sectional survey established on the Finnvasc
      registry. SETTING: Multicentre, Finland. MATERIAL: 7616 vascular procedures
      consisted of 5201 open vascular operations and 2415 endovascular interventions
      done during the two years 1991-92. MAIN OUTCOME MEASURES: Mortality and number of
      reoperations and major amputations. RESULTS: A total of 5409 initial vascular
      procedures were done, 770 patients (10%) underwent a new procedure in the same
      anatomical segment as previously, and 1437 patients (19%) underwent a vascular or
      endovascular procedure on a new arterial segment excluding the coronary arteries;
      these patients had more risk factors than the two other groups, and were also
      treated more often for chronic leg ischaemia. Altogether 586 reoperations were
      needed in 487 patients (6%) during a 30-day postoperative period, more often
      after the initial surgical reconstruction than on other occasions. Altogether 126
      postoperative below-knee and 170 above-knee amputations had to be done during the
      same period which corresponded to 14% of the total of 2128 surgical or
      endovascular revascularisations done for acute or chronic critical leg ischaemia.
      The risk of perioperative death was higher in patients with acute leg ischaemia
      undergoing their first vascular intervention than those having repeat operations.
      CONCLUSION: Although the present data are cross-sectional and might be affected
      by the recent increase in vascular surgery in Finland they show that almost a
      third of vascular operations done are repeat procedures.

PMID- 8739415
TI  - Increased concentrations of cytokines and adhesion molecules in patients after
      repair of abdominal aortic aneurysm.
AB  - OBJECTIVE: To evaluate the association between inflammatory mediators and
      clinical outcome in patients after repair of abdominal aortic aneurysms. DESIGN:
      Prospective study. SETTING: University hospital, The Netherlands. PATIENTS: 30
      Consecutive patients who had undergone elective or acute repair of abdominal
      aortic aneurysms. MAIN OUTCOME MEASURES: Plasma concentrations of the cytokines
      tumour necrosis factor (TNF), interleukin-6 (IL-6) and interleukin-8 (IL-8) as
      well as soluble TNF receptors and the soluble (s) adhesion molecules E-selectin
      and intercellular adhesion molecule 1 (ICAM-1) were measured and correlated with
      the degree of systemic hypotension (shock: hypotension more than 15 minutes) and
      clinical outcome. RESULTS: Peak plasma concentrations of TNF and IL-6 were
      significantly higher in shocked patients (p < 0.005 and p < 0.0005, respectively)
      and those who died (both p < 0.01), whereas concentrations of IL-8 increased only
      when shock complicated rupture of the aneurysm (p < 0.01). Increases in the
      concentrations of TNF receptors reflected impaired renal function. In contrast to
      sE-selectin concentrations, peak sICAM-1 concentrations were significantly higher
      in shocked patients (p < 0.01) and those that died (p < 0.01). CONCLUSIONS: These
      results strongly suggest that increased concentrations of sICAM-1 and IL-6
      reflect the inflammatory response induced by ischaemia after repair of an
      abdominal aortic aneurysm, and indicate that the postoperative course is likely
      to be complicated.

PMID- 8739416
TI  - Factors affecting the lifespan of autologous and synthetic arteriovenous access
      routes for haemodialysis.
AB  - OBJECTIVE: To try and establish a consensus about the ideal secondary access for
      haemodialysis by assessing factors that affect the longevity of various access
      routes. DESIGN: Multicentre survey, by questionnaire. SETTING: General hospital,
      Athens. SUBJECTS: All 1516 patients in the Athens area receiving chronic
      haemodialysis. MAIN OUTCOME MEASURES: Longevity of present and any previous
      access routes (n = 2323). Data including type of access, age, sex and the
      existence of diabetes, hypertension, hyperlipidaemia, or other systematic
      diseases were recorded. RESULTS: Some 1220 (80%) of the patients were using
      autologous access, 1049 (69%) arteriovenous (AV) fistulas at wrist and 171 (11%)
      at elbow. Variables were analysed using Cox's proportional hazard model. Age and
      female sex were significantly associated with failure of autogenous access (p <
      0.001) although not affecting synthetic grafts. Autogenous fistula at the elbow
      was the only secondary access that was less likely to fail than the initial
      (baseline) fistula at the wrist. Among the various grafts, straight arm grafts
      had the best prognosis and straight forearm grafts were the most likely to fail
      (p < 0.001). CONCLUSION: An AV fistula at the elbow should be considered the
      second best after the fistula at wrist, but is not always feasible. A synthetic
      graft is more likely to be needed in elderly patients and women, in whom an
      autogenous AV fistula is more likely to fail.

PMID- 8739417
TI  - Gastro-oesophageal reflux before and after vertical banded gastroplasty in the
      treatment of obesity.
AB  - OBJECTIVE: To study the long term effect of vertical banded gastroplasty on lower
      oesophageal sphincter pressure. DESIGN: Prospective study. SETTING: University
      hospital, Sweden. SUBJECTS: 21 morbidly obese patients (mean body mass index
      42.5). INTERVENTIONS: Vertical banded gastroplasty, together with measurements of
      endoscopic grade, oesophageal manometry, and 24 hour pH before, and a mean of 38
      months after, operation. MAIN OUTCOME MEASURES: Weight, grade of oesophagitis
      according to the Savary-Miller classification, number of episodes of reflux,
      percentage of time that the pH was < 4, and lower oesophageal sphincter pressure.
      RESULTS: Before operation 5/14 patients (36%) had evidence of oesophagitis, and
      12/21 (57%) had evidence of reflux disease. Two patients had abnormally low lower
      oesophageal sphincter pressure ( < 10 mm Hg). A mean (SEM) of 32 months after
      operation (range 6-49) the mean body mass index was 32.7 (1.2), and after a mean
      of 38 months paired data showed that there had been no significant changes in
      manometric (n = 11) or 24 hour pH (n = 10) measurements, or in endoscopic grading
      (n = 7). CONCLUSION: Vertical banded gastroplasty used in the treatment of morbid
      obesity does not affect the antireflux function of the lower oesophageal
      sphincter.

PMID- 8739418
TI  - Outcome after surgery for biliary pancreatitis.
AB  - OBJECTIVE: To correlate the results of operations for the treatment of biliary
      pancreatitis with the timing of the operation. DESIGN: Retrospective study.
      SETTING: University hospital, Germany. SUBJECTS: 81 Consecutive patients who were
      operated on for biliary pancreatitis of the 106 who presented to the department
      between 1981 and 1990. INTERVENTIONS: Cholecystectomy, with or without
      exploration of the common duct, together with no operation on the pancreas,
      exploration, or drainage and necrosectomy. MAIN OUTCOME MEASURES: Correlation of
      outcome with timing of operation after the onset of the pancreatitis (early,
      within 72 hours; delayed, 3-14 days; or elective, after 14 days). RESULTS: 37
      Patients (46%) were operated on early; in 27 (33%) the operation was delayed; and
      in 17 (21%) it was elective. Timing correlated with outcome-22 patients (59%) of
      those operated on early developed a complication together with 12 (27%) of those
      in the delayed and elective groups (p < 0.005). The overall mortality was 12%
      (10/81). Multiple regression analysis showed that the timing of the operation and
      the severity of the pancreatitis were less important prognostic factors than the
      patient's age and the extent of pancreatitic operation (p < 0.005). The
      complication rate was 15/56 (27%) after none or exploration of the pancreas,
      compared with 19/25 (76%) after drainage or necrosectomy (p < 0.005). CONCLUSION:
      Aggressive pancreatic surgery increases the risk of morbidity whereas extent of
      biliary surgery has no influence. Postponing the biliary operation until after
      the acute attack reduces the need for early exploration and drainage of the
      pancreas.

PMID- 8739419
TI  - Restorative compared with conventional proctocolectomy for the treatment of
      ulcerative colitis.
AB  - OBJECTIVE: To evaluate the clinical differences between conventional and
      restorative proctocolectomy in the treatment of ulcerative colitis. DESIGN:
      Retrospective analysis. SETTING: University hospital, Finland. SUBJECTS: 240
      consecutive patients with ulcerative colitis who underwent elective
      proctocolectomy between 1976 and 1990. INTERVENTIONS: Proctocolectomy and
      conventional ileostomy (n = 119) or restorative proctocolectomy (n = 121). MAIN
      OUTCOME MEASURES: Early and late surgical morbidity and recovery time. RESULTS:
      There were no postoperative deaths after restorative proctocolectomy and one
      patient (1%) died after conventional proctocolectomy. Two other patients (2%)
      with ileostomies died of late complications. Delayed perineal would healing after
      conventional ileostomy (n = 45, 38%) and either early (n = 31, 26%) or late (n =
      19, 16%) defects of the ileoanal anastomosis after restorative proctocolectomy
      caused most problems. Reoperations (early or late) were needed in 45 (38%) and 44
      (36%) patients after Brooke ileostomy and restorative proctocolectomy,
      respectively. Major complications, however, were more common and the duration of
      sick leave was a month longer in the pouch group. CONCLUSION: Ulcerative colitis
      can safely be managed with either conventional or restorative proctocolectomy. In
      most cases the patient's preference should dictate the choice of procedure.

PMID- 8739420
TI  - Postocclusive hyperaemia in skin measured in pigs by laser Doppler: influence of
      site of arterial stenosis in the limb.
AB  - OBJECTIVE: To investigate how site and severity of arterial stenosis, and
      distance between tourniquet and measuring probe influences the postocclusive
      hyperaemic response in limb skin recorded by laser Doppler. DESIGN: Open study.
      MATERIAL: Nine Norwegian Landrace pigs. INTERVENTION: Experimental stenoses in
      the abdominal aorta, the external iliac and femoral arteries. The hyperaemic
      responses were recorded with the probe at two different distances from the
      tourniquet. MAIN OUTCOME MEASURES: Curve pattern, relative reduction in flux
      between the two peaks in double humped curves, and time to peak hyperaemic flux.
      RESULTS: Double humped curves were produced at all sites, but the blood pressure
      gradient required at the stenosis was greater the more proximal the stenosis. In
      distal stenoses there was a greater relative reduction in flux between the two
      peaks (p < 0.05). The time to peak hyperaemic flux was related to the gradient of
      the stenosis (mmHg) (r = 0.62, p < 0.0001), but was independent of its site.
      Increased distance between the tourniquet and the probe gave lower laser Doppler
      amplitudes and prolonged the time to peak hyperaemia in experiments with femoral
      artery stenosis (p < 0.05). CONCLUSION: The hyperaemic response is governed by
      both the severity and the site of arterial stenosis. Stenoses distal to the
      tourniquet seem to impair the initial reperfusion more than comparable lesions
      proximal to the tourniquet. Time to reach peak hyperaemia is the single variable
      most closely related to the severity of the stenosis.

PMID- 8739421
TI  - Effect of sodium nitroprusside on cerebral haemodynamics during cross-clamping of
      the descending thoracic aorta in pigs.
AB  - OBJECTIVE: To assess the effect of sodium nitroprusside on cerebral haemodynamics
      during cross-clamping of the descending thoracic aorta in pigs. DESIGN: Non
      randomised controlled animal study. SETTING: University hospital, Norway.
      MATERIAL: 17 Pigs. INTERVENTIONS: Cross-clamping of the descending thoracic aorta
      for 30 minutes. In 8 pigs sodium nitroprusside was given to prevent proximal
      hypertension (sodium nitroprusside group); 9 pigs were given no sodium
      nitroprusside (control group). MAIN OUTCOME MEASURES: Intracerebral pressure,
      sagittal sinus pressure, cerebral flux, and internal carotid artery blood flow.
      RESULTS: Intracerebral pressure, sagittal sinus pressure, and cerebral flux
      increased in both groups during cross-clamping of the descending thoracic aorta.
      There were no differences between the groups in these variables despite
      significantly lower mean proximal aortic pressure in the sodium nitroprusside
      group. CONCLUSIONS: Sodium nitroprusside did not affect intracerebral pressure,
      sagittal sinus pressure, or cerebral flux during cross-clamping of the descending
      thoracic aorta. Increased cerebral blood flow rather than venous congestion is
      the most likely cause of increased intracranial pressure during cross-clamping of
      the descending thoracic aorta.

PMID- 8739422
TI  - A novel use for the Port-a-Cath: pneumoperitoneum in the repair of giant hernia.

PMID- 8739423
TI  - Degeneration and sarcomatous transformation of a retroperitoneal leiomyoma.

PMID- 8739424
TI  - Multiple compartment syndrome after childbirth.

PMID- 8739425
TI  - "Acute appendicitis" of neurosurgical origin.

PMID- 8739426
TI  - Hernia through a scar on the posterior rectal wall.

PMID- 8739427
TI  - Closure of the abdominal wall after major gastrointestinal operations.

PMID- 8739428
TI  - Teaching of anatomy: a job for a biologist or a surgeon?

PMID- 8739429
TI  - Pilonidal care: anaerobes as invisible villains.

PMID- 8739430
TI  - Quality of life as a measure of rehabilitation outcome in patients with multiple
      sclerosis.
AB  - A total of 43 patients with multiple sclerosis (MS) consecutively admitted to the
      Multiple Sclerosis Rehabilitation Hospital in Haslev completed a Danish version
      of the Laman & Lankhorst Questionnaire (LLQ) on quality of life (qol), and the
      Beck Depression Inventory (BDI). Twenty-one of the 43 pts completed the
      questionnaires at discharge as well. All patients received the standard
      multidisciplinary rehabilitative treatment. The purpose was to evaluate the LLQ
      as a measure of qol and as an outcome measure. The 43 MS-patients had low
      weighted qol scores on the following items: readily tired, fatigue, dependence on
      other people, worry about deterioration and walk. Correspondingly, the BDI showed
      high scores on fatigability, work difficulty and somatic preoccupation. The
      correlation between LLQ and BDI was statistically significant (0.54, p < 0002),
      but weak. ANOVA with repeated measures (LLQ and BDI at admission and discharge)
      was applied to evaluate rehabilitation outcome in 21 patients. LLQ: The patients
      experienced a significant reduction in disability on fatigue and mood; and in the
      importance of being able to climb stairs and to work. The weighted qol-scores
      increased significantly on physical endurance, work and mood. BDI scores showed a
      significant decrease on pessimism, irritability, loss of libido and total BDI
      score. The changes measured by the LLQ were mainly on behavioral aspects. As the
      correlation coefficient was only 0.54, the LLQ and the BDI seem to address
      different aspects of quality of life.

PMID- 8739431
TI  - A repetitive DNA sequence 5' to the human myelin basic protein gene may be linked
      to MS in Danes.
AB  - The myelin basic protein (MBP) gene is a candidate locus for disease
      susceptibility in multiple sclerosis (MS). In the present study a part of the
      tetranucleotide (TGGA)n repeat polymorphism 5' to the MBP gene was examined in 90
      Danish MS patients and 106 controls. Lymphocyte DNA was isolated and used in PCR
      assay. The PCR fragments produced were separated by agarose and acrylamide
      electrophoresis. Hereby we found three different bandpatterns i.e. a homozygote
      with a 450 bp fragment, a homozygote with a fragment 375 bp and a heterozygote
      with both bands present. The 450 bp fragment occurred significantly more often
      among MS than in the control group and the 375 bp fragment was underrepresented
      among MS than in the control group. The differences between incidence of the
      three band pattern in the MS and the control group were significant different at
      1% level. Our study thus indicate that there is an association between MS and a
      length polymorphism of the 5' end to the MBP gene in Danish MS patients.

PMID- 8739432
TI  - Power spectrum analysis contribution to the detection of cardiovascular
      dysautonomia in multiple sclerosis.
AB  - In multiple sclerosis (MS) autonomic cardiovascular dysfunction is an uncommon,
      but potentially dangerous event, to which studies of spectral analysis of heart
      rate variability have not been applied, yet. MATERIAL AND METHODS--We studied 16
      patients with definite MS (11 women and 5 men, mean age 30.3 +/- 7.4 yrs., mean
      EDSS 2.06 +/- 1.42) and 16 sex- and age-matched healthy controls. Besides
      cardiovascular reflex tests (valsalva manoeuvre, deep breathing, lying to
      standing, Blood Pressure response to standing and sustained handgrip), each
      underwent spectral analysis of the R-R interval short-term variability at rest
      and after tilting, to detect three components: very low frequency (VLF), low
      frequency (LF) and high frequency (HF). A recent brain MRI was obtained from
      patients, to compare plaque characteristics with spectral parameters. RESULTS--At
      cardiovascular reflexes, only four patients (25%) showed an impairment, mostly of
      a mild degree. VLF and LF at rest were lower in MS subjects than in controls (p <
      0.01). No significant correlation was found between spectral parameters and
      lesion area or localization as detected on MRI. CONCLUSIONS--Spectral analysis
      could usefully flank reflex tests to detect autonomic subclinical cardiovascular
      abnormalities.

PMID- 8739433
TI  - Serial MRI, VEP, SEP and biotesiometry in acute optic neuritis: value of baseline
      results to predict the development of new lesions at one year follow up.
AB  - INTRODUCTION: In an attempt to establish the value of MRI, VEP, SEP, and
      biotesiometry in monitoring disease evolution we undertook a one year follow up
      study of 70 untreated patients with acute optic neuritis (ON). MATERIAL &
      METHODS: ON was monosymptomatic in 48 patients (bilateral in 10) and part of
      clinically definite multiple sclerosis (CDMS) in 22 patients, examined as
      mentioned below. RESULTS: Results are given at onset and at follow up (in
      brackets). In monosymptomatic ON, brain MRI was abnormal in 53% (53%), VEP in the
      eye with acute ON in 79% (71%), VEP in the clinically unaffected eye in 34%
      (47%), SEP in 25% (23%), and biotesiometry in 29% (17%). In CDMS, brain MRI was
      abnormal in 95% (95%), VEP in the eye with acute ON in 86% (77%), VEP in the
      clinically unaffected eye in 50% (64%), SEP in 55% (50%), and biotesiometry in
      63% (53%). Only minor changes in test scores were observed after one year except
      for significant improvement of VEP in eyes with acute ON. Eight of 32 patients,
      characterized by at least one abnormal paraclinical test at onset of
      monosymptomatic ON, had developed CDMS versus none of 16 patients with normal
      paraclinical results (p = 0.03; Fisher). CONCLUSION: Patients with
      monosymptomatic ON with paraclinical signs of multifocal involvement at onset had
      an increased risk of developing CDMS. No single test predicted the evolution of
      CDMS, perhaps due to the relatively short follow up time.

PMID- 8739434
TI  - Effect of epilepsy, seizures and epileptiform EEG discharges on cognitive
      function.
AB  - Patients with an established diagnosis of epilepsy were included in three groups
      on the basis of the absence (Group 2) or presence (Group 3) of epileptiform EEG
      discharges or subtle seizures (Group 4) during the cognitive assessment
      procedure. A separate age-matched non-epileptic control group (Group 1) was
      formed. Twenty-five patients were included in each of the four groups. Thus, a
      total of 100 patients were investigated. The patients were assessed with
      continuous 21-channel EEG and video-monitoring, combined with cognitive testing.
      The results show consistently lower performance on cognitive tests for Group 4,
      the group with subtle seizures. The difference with the control group was
      significant for the intelligence subtests and for the complex information
      processing test (p < 0.05). No transient cognitive impairment was found. The
      results are discussed in the light of possible factors that may be responsible
      for the lower test-scores in the patients of Group 4: both the ictal effects of
      the seizures themselves, postictal effects and the effects of the epileptiform
      EEG discharges may have had an impact on cognitive performance. Finally the
      absence of evidence for transient cognitive impairment in a group with frequent
      epileptiform EEG discharges is discussed in detail.

PMID- 8739435
TI  - Myasthenia gravis in the elderly: a hospital based study.
AB  - To evaluate clinical characteristics and outcome of myasthenia gravis (MG) in
      aged patients (> 60yrs), we retrospectively reviewed a continuous series of 122
      myasthenic patients observed from January 1968 through December 1994. Patients
      with congenital, neonatal, or penicillamine-induced myasthenia were excluded.
      Twenty-five subjects (20%) were > 60yrs. The male/female ratio was 3:2; 20% of
      patients had an ocular form and 86% were seropositive. Mediastinum CT scan
      revealed thymic changes in 14%. During the first five years of disease, 60% of
      patients with ocular form progressed towards a generalized form and 15% had
      clinical relapses. At the time of their last visit, 40% of patients were
      asymptomatic and 60% had improved on medication. No patient died because of
      myasthenia-related causes. This study shows that MG in aged patients is
      characterized by prevalence in males, low frequency of ocular forms, low
      frequency of positive mediastinum CT which suggests low frequency of thymomas,
      high frequency of progression of ocular forms, and good response to
      corticosteroid therapy.

PMID- 8739436
TI  - Myasthenia gravis and primary biliary cirrhosis. Common immunological features
      and rare coincidence.
AB  - A 43-year-old woman with recently diagnosed primary biliary cirrhosis developed
      antibody-negative myasthenia gravis. She did not receive D-penicillamine therapy.
      Clinical and immunological features of this patient are discussed. In previous
      reports on an association between primary biliary cirrhosis and myasthenia D
      penicillamine treatment was an obligate causal linkage between both disorders.

PMID- 8739437
TI  - Multimodal evoked potentials in HIV-1-seropositive patients: relationship between
      the immune impairment and the neurophysiological function.
AB  - Multimodal evoked potentials (PRVEP, BAEP, mSEP) were recorded in 56 HIV-1
      seropositive outpatients free from opportunistic CNS pathologies and/or overt HIV
      1 encephalopathy. EPs were altered in 17 of 39 (43.6%) seropositive subjects
      without AIDS (group A) and in 13 of 17 (76.5%) patients with AIDS (group B). A
      high incidence of subclinical alterations (30.8%) were found in group A patients.
      Significant BAEP (I-III, III-V, I-V) interpeak latency and mSEP (N9-N13, N9-N20)
      conduction time prolongations were found in group A and B patients. PRVEP P100
      was significantly prolonged only in group B. An inverse relationship between BAEP
      interpeak latencies and CD4 count was found. Our findings support the hypothesis
      of an important role of immunodepression in the development of neurophysiologic
      abnormalities, together with a preferential involvement of acoustic pathways, in
      the course of HIV-1 infection.

PMID- 8739439
TI  - Oculopharyngeal muscular dystrophy in Norway. Survey of a large Norwegian family.
AB  - OBJECTIVES: Oculopharyngeal muscular dystrophy was first described by Taylor in
      1915. A substantial number of cases have been reported from North America, the
      disorder being most frequent in Quebec, Canada. MATERIAL: The onset of disease is
      in middle life, most often presenting with ptosis and a slight degree of
      ophthalmoplegia, followed some years later by dysphagia and often by proximal
      limb weakness. The course is slowly progressive, but the dysphagia may become
      severe and has caused death by starvation in several cases. The disorder is
      transmitted autosomally dominant in families. RESULTS: The present report
      describes a large Norwegian family with 13 affected members of whom we have
      examined eight. Transmission is autosomally dominant, mode of presentation may be
      either by ptosis or by dysphagia. In rare cases gait difficulties may be the
      presenting symptom. CONCLUSION: Electromyographic and muscle biopsy examinations
      demonstrate a primary myogenic disorder.

PMID- 8739438
TI  - Naming deficit in herpes simplex encephalitis.
AB  - OBJECTIVES: The preferential involvement of living categories in naming
      impairment is well recognised in Herpes Simplex Encephalitis (HSE). In this paper
      we describe naming, neuropsychological and neuroradiological findings with seven
      fresh HSE cases. MATERIAL & METHODS: Patients were given a picture naming task
      that included 60 items belonging to 6 different categories (three living, i.e.
      fruits, vegetables and animals and three non-living, i.e. furniture, vehicles and
      tools). In the statistical analysis several possible sources of bias as the
      frequency of the target word, the familiarity with the objects to name, the image
      complexity and other parameters were taken into account. RESULTS: Four out of
      seven patients were significantly more impaired with living things. We describe
      their general cognitive profile and discuss the anatomo-functional aspects of
      category dissociation. CONCLUSION: Language impairment, disproportionately severe
      for the naming of living exemplars, is frequently observed in HSE, is clinically
      relevant and should be specifically investigated.

PMID- 8739440
TI  - Asymptomatic cervical artery stenoses in Moscow.
AB  - The risk of stroke related to asymptomatic carotid artery stenosis is known to be
      increased in high-grade or rapidly progressive stenosis. Information of the
      prevalence in the general population is required for the recommendation of
      screening methods to detect patients needing prophylactic treatment. We studied
      the prevalence and the grade of severity of extracranial carotid and vertebral
      artery obstructions by means of Doppler sonography in 529 asymptomatic Russians
      (m: 343, f: 186; 36-84 years, mean: 58.4 years) living in Moscow city. Internal
      carotid artery obstructions of more than 50% stenosis were present in 22 (= 4.2%)
      subjects, 8 of them (1.5%) had bilateral lesions. Appropriate abnormal findings
      in vertebral arteries were found in 11 (= 2.1%) subjects, in 1 of them
      bilaterally. Affection of both the carotid and the vertebral arteries was noted
      in 4(= 0.8%) individuals. There were no sexual differences. The risk factor which
      correlated most significantly with cervical arterial lesions was hypertension.
      Carotid lesions were also significantly associated with age and smoking, but not
      with diabetes or hyperlipoproteinemia. The prevalence of cervical artery stenoses
      was found to be lower than in western reports, which may be due to different
      technical equipment and different study design.

PMID- 8739441
TI  - Incidence of transient ischemic attacks in the Belluno Province, Italy. First
      year results of a community-based study.
AB  - OBJECTIVES: This study formed part of a larger prospective population-based
      survey on cerebrovascular diseases and aimed to provide reliable and comparable
      results on TIA incidence and on related risk factors, which could supply
      investigation objectives and support information for primary and secondary
      prevention. MATERIAL AND METHODS: We undertook a prospective population-based
      study in the province of Belluno, an area located in the North-East of Italy
      where 211,389 people live, utilizing all the possible case-collection sources
      available in the territory. RESULTS: In the first year of the study (June 1, 1992
      to May 31, 1993) 271 patients with a diagnosis of transient ischemic attack were
      recruited. Among these, we recorded 171 cases of new TIAs. The crude annual
      incidence rate for new TIAs was 0.80 per 1000, 0.73 per 1000 for men and 0.87 per
      1000 for women. After adjustment to the European population, the overall
      incidence rate decreased to 0.58 per 1000 inhabitants per year. The mean age of
      new TIA patients was 73.91 years and females were significantly older than males
      (p < 0.001). A CT scan disclosed an infarct in 21 new TIA patients. CONCLUSION:
      Our first-year results on new TIAs incidence did not differ from the findings
      reported in previous population-based studies performed throughout the world and
      support data as to risk factors for TIA.

PMID- 8739442
TI  - Specific cardiological evaluation after focal cerebral ischemia.
AB  - Purpose of this study was to define a subgroup of TIA/stroke patients who should
      be examined by transthoracal and transesophageal echocardiography or Holter
      electrocardiography to identify those with cardiogenic brain embolism reliably;
      300 consecutive patients with acute focal brain ischemia underwent a standardized
      diagnostic protocol for the evaluation of the etiology including, clinical
      examination by a cardiologist and routine electrocardiography, Holter
      electrocardiography, transthoracal and transesophageal echocardiography. 188
      patients had a potential cardiac source of embolism. In particular
      echocardiography was diagnostic in 163 patients, and Holter-electrocardiography
      10; 159 of these 188 patients (84.6%) had competitive etiologies, predominantly
      large vessel atherosclerosis. In 136 patients cardiogenic brain embolism was
      assumed as quite definite or possible. To identify these patients reliably,
      transthoracal and transesophageal echocardiography would have been necessary in
      89% of the entire group of patients (all with clinically cardiological
      abnormalities, pathological routine ECG, without vascular risk factors, or no
      atherosclerosis in duplex sonography), and Holter-electrocardiography in 54%.

PMID- 8739443
TI  - Startle syndrome: the blink reflex study suggests the private involvement of
      lower brainstem in the pathophysiology.

PMID- 8739444
TI  - Immunodystrophism, T cells, cytokines, and pregnancy failure.

PMID- 8739445
TI  - Placental interferons.
AB  - Trophectoderm of ruminant conceptuses (embryo and associated membranes) secrete
      tau interferons (IFN tau) as the pregnancy recognition signal. Secretion of IFN
      tau on gestational days 12-13 for sheep and gestation days 14-17 for cows and
      goats is critical for pregnancy recognition. IFN tau acts on uterine epithelium
      to suppress estrogen receptor and oxytocin receptor gene expression, which
      prevents uterine release of luteolytic pulses of prostaglandin F2 alpha (PGF).
      Expression of the progesterone receptor (PR) gene in uterine endometrium is not
      affected by oIFN tau. Maintenance of progesterone secretion by the corpus luteum
      (CL) ensures establishment of pregnancy. Pig conceptuses secrete both IFN alpha
      and IFN gamma between days 15-21 of gestation, but their role(s) in early
      pregnancy is unknown. Estrogen secreted by pig trophoblast between gestational
      days 11-13 and 15-25 increases endometrial receptors for prolactin and causes
      exocrine secretion of PGF into the uterine lumen to prevent luteolysis. Shared
      cell-signaling mechanisms by IFNs and lactogenic hormones through Janus kinases
      (JAK) 1 and 2 may provide a common pathway to abrogate luteolytic mechanisms to
      ensure establishment of pregnancy. The role(s) of IFNs produced by human and
      rodent placentae is not known.

PMID- 8739446
TI  - Functional characteristics of human trophoblast interferons.
AB  - Human trophoblast populations from first-and third-trimester placentas produce
      interferons (IFNs) in the presence of growth factors (CSF and PDGF) or when
      infected with virus. The highly invasive extravillous trophoblast population
      produced a higher level of IFNs (three- to eightfold, P < 0.05) than the
      noninvasive villous trophoblast population when stimulated with growth factors
      and/or virus. The level of IFN produced was dependent on the type of trophoblast
      population, the type of inducer and the stage of differentiation of the
      trophoblasts. Tandem immunoaffinity chromatography of the virus-induced
      trophoblast IFNs resulted in the isolation of trophoblast IFN-alpha and -beta
      types. The purified trophoblast IFNs have antiviral, antiproliferative and
      immunoregulatory properties. Furthermore, the trophoblast IFNs inhibited the
      expression of proto-oncogenes such as EGF-R, c-erbB2 and c-fms reported to be
      involved in normal trophoblast growth and differentiation. These data suggest
      essential roles of interferons in normal human development during pregnancy.

PMID- 8739447
TI  - Control of cell proliferation by embryonal-origin factors.
AB  - Embryogenesis can be paralleled and contrasted with cancerous cell proliferation;
      both embryogenesis and cancer are associated with extremely rapid cell
      proliferation. However, unlike cancer, embryogenesis is characterized by a
      delicate balance of proliferative and anti-proliferative processes. We have found
      two chromatographically separated fractions derived from human embryonal neural
      tissue extracts that significantly suppress the proliferation of human breast
      cancer cells. The reduction in cell number was time dependent, with maximal
      inhibition (70%) observed after 4 days of incubation while maintaining cell
      viability. The anti-proliferative effect was also evidenced by decreased [3H]
      thymidine incorporation. Significant inhibition of proliferation of osteosarcoma,
      fibrosarcoma, and Balb/c 3T3 cell lines was also obtained with a low
      concentration of the active fractions. Embryonal factors inhibited mouse and rat
      cell lines, indicating cross-species effectiveness. The SDS-PAGE of the
      biologically active approximately 10.7 kDa region revealed several protein bands,
      while the biologically active approximately 4.5 kDa fraction contained only
      weakly stainable bands. Thus, the embryo contains factors that control the
      proliferation of malignant cells. These potent and possibly novel compounds
      should be investigated for their potential therapeutic role in cancer and other
      proliferative disorders.

PMID- 8739448
TI  - The emerging role of IL-10 in pregnancy.

PMID- 8739449
TI  - Psycho-neuro-cytokine/endocrine pathways in immunoregulation during pregnancy.
AB  - PROBLEM: Some mammalian pregnancy failure is thought to occur by immunological or
      immunologically modifiable mechanisms. The original model wherein spontaneous
      abortion was proposed to represent rejection of the conceptus as an allograft has
      been supplanted by a model of maternal paraimmunological natural effector cell
      toxicity to fetal trophoblast more closely related to tumor rejection. The
      problem is to integrate current information concerning the role of immunological,
      paraimmunological, endocrinological, and stress-triggered neural factors that
      determine whether or not abortion will occur. METHODS: Review of existing data.
      RESULTS: An integrated model is proposed. CONCLUSION: Immunological factors play
      an important role in abortion processes and prevention of abortions. The
      existence of abortogenic mechanisms and their regulation appears to be based upon
      optimizing survival of the species. Two new conceptual models provide a useful
      framework for further investigation of human pregnancy failure and its treatment.

PMID- 8739450
TI  - TJ6: the pregnancy-associated cytokine.
AB  - These studies have demonstrated that TJ6m protein can be measured in women prior
      to a spontaneous abortion based on expression of TJ6 on CD56-positive NK cells.
      This suggested to us a possible regulator function for TJ6 during pregnancy. We
      have shown that in T cells only crosslinking of the T-cell receptor can
      upregulate TJ6 expression and the other activators, such as mitogens, do not. A
      clear discrepancy in the pattern of expression of TJ6 on CD56 and CD19-positive
      cells was noted between successful and unsuccessful pregnancies. A successful
      pregnancy is denoted by TJ6 expression on B cells, whereas in a potential
      spontaneous abortion there is TJ6 expression on both NK and B cells.

PMID- 8739452
TI  - The immunological pregnancy protective effect of progesterone is manifested via
      controlling cytokine production.
AB  - PROBLEM: This study was aimed at investigating the involvement of an altered
      cytokine pattern in the immunomodulatory and anti-abortive effects of a
      progesterone-induced immunomodulatory protein (PIBF). METHOD: PIBF expression on
      lymphocytes of healthy pregnant women and from women at risk for premature
      pregnancy termination was determined. In sera of the same women TNF alpha was
      quantified by a bioassay using L929 cells. NK activity was determined by a single
      cell cytotoxicity assay. Cytokine production of the lymphocytes or murine spleen
      cells was measured by ELISA or detected by immunocytochemistry. In pregnant mice
      endogenous PIBF activity was neutralized by anti-PIBF IgG. RESULTS: Sera of women
      at risk for premature pregnancy termination contained significantly higher
      concentrations of TNF alpha than those from healthy pregnant women and PIBF
      expression on the lymphocytes was inversely related to serum concentration of TNF
      alpha. Increased NK activity of lymphocytes after neutralization of endogenous
      PIBF activity is corrected by anti-IL 2 treatment and PIBF inhibits IL 12
      expression on activated lymphocytes. PIBF increases IL-10 production by activated
      spleen cells. In pregnant mice, neutralization of endogenous PIBF activity by
      specific antibody results in increased resorption rate and reduced splenic IL-10
      production. CONCLUSIONS: Our data allow the assumption that via blocking IL-12
      production PIBF inhibits NK activation with a concomitant reduction of TNF alpha
      levels. Disturbances in this system might lead to the expression of the known
      synergistic effect of IL-12 and TNF alpha, resulting in a Th 1 type cytokine
      dominance and pregnancy termination.

PMID- 8739451
TI  - Transforming growth factor-beta 2-related-decidual suppressor factor is not
      related to TJ6 protein.
AB  - Transforming growth factor (TGF)-beta 2-related-decidual suppressor factor (DSF)
      and TJ6 protein are both immunosuppressive molecules present in murine and human
      pregnancy. Treatment of mice with either anti-TJ6 or anti-TGF-beta 2 neutralizing
      antibodies results in increased fetal loss. Western blots of supernatants from
      pregnant mouse decidua probed with anti-TJ6 (soluble form) showed a doublet at a
      similar molecular size as when the blot was probed with anti-TGF-beta 2 antibody.
      The problem is to determine whether TJ6 and DSF are the same protein. In order to
      determine if TJ6 and DSF are the same or different proteins, we used affinity
      column purified TGF-beta 2-DSF and stained Western blots with anti-TJ6. The TGF
      beta 2-monoclonal antibody affinity column-purified DSF that stained with anti
      TGF-beta 2 was not reactive with anti-TJ6 antibody. TJ6 has only a 30% gene
      sequence homology and a 13% amino acid homology to TGF-beta 2. TJ6 and TGF-beta 2
      related DSF appear to be different immunosuppressive proteins in decidua.

PMID- 8739453
TI  - Immunotherapy for recurrent pregnancy loss: analysis of results from clinical
      trials.
AB  - PROBLEM: Up to 80% of unexplained recurrent spontaneous abortions (RSA) are
      thought to have an immunologic mechanism. Yet clinical trials using immunotherapy
      to treat women experiencing RSA have low treatment effects. The present study was
      undertaken to explain the low treatment effects. METHODS: Results of clinical
      trials using allogeneic leukocyte immunization and intravenous (IV)
      immunoglobulin (Ig) are compared. The mechanisms of pregnancy loss are reviewed
      in light of data on frequency of karyotype abnormalities in trophoblast of
      failing pregnancies. RESULTS: Results of two independent analyses using
      allogeneic leukocyte immunization as immunotherapy for all women with RSA
      revealed live birth ratios of 1.16 (P = 0.03) and 1.21 (P = 0.02). When the
      analysis was limited to primary aborters, the live birth ratio increased to 1.46
      (P = 0.006). Live birth ratio after immunotherapy for all RSA using IVIg was 1.88
      (P = 0.04). Because of low treatment effects, confounders to treatment success of
      maternal age and number of previous abortions were studied. Chromosomal
      abnormalities have been identified in 55% of concepti from RSA. The frequency of
      chromosomal abnormalities remained constant for up to six pregnancy losses. Women
      with a history of primary compared to secondary RSA had a higher frequency of
      karyotypically abnormal concepti (chi 2 = 4.54, P < 0.05). Risk factors for RSA
      also include number of previous losses. CONCLUSION: Chromosomal abnormalities are
      a significant confounder when evaluating efficacy of immunotherapy for treatment
      of RSA. Some women with RSA have a high risk of recurrent chromosomal problems.

PMID- 8739454
TI  - Intravenous immunoglobulin in women with five or more abortions.
AB  - PROBLEM: Treatment for recurrent miscarriage has usually been given to all women
      with three or more abortions of unknown cause. As these patients have a 50-60%
      subsequent live birth rate, no treatment has been shown to unequivocally improve
      the live birth rate. Immunoglobulin is the latest treatment to be applied. In
      order to determine if immunoglobulin improves the live birth rate, we analyzed
      the results of patients expected to have a poor outcome in the subsequent
      pregnancy if left untreated, i.e., women with five or more abortions, who have
      aborted after paternal leucocyte immunization or who continue to abort despite
      possessing anti-paternal complement dependent antibody (APCA). METHODS: A
      preliminary trial was carried out using immunoglobulin (Sandoglobulin, Sandoz,
      Switzerland). It was infused at a dose of 400 mg/Kg body weight, in the
      follicular phase of a cycle in which pregnancy was planned. A booster dose was
      administered as soon as pregnancy was diagnosed. RESULTS: Twelve patients were
      treated, ten conceived. Five have had subsequent live births. Two infants were
      premature but their size was appropriate for gestational age. The other three
      infants delivered at term. CONCLUSIONS: This is still too small a group from
      which to draw definite conclusions about the efficacy of immunoglobulin to
      prevent abortion. However, five live births in ten patients is an encouraging
      result, especially when the expected poor obstetric outcome is considered. Hence
      the efficacy of immunoglobulin should be evaluated further in high risk patients.

PMID- 8739455
TI  - Elevated peripheral blood natural killer cells are effectively downregulated by
      immunoglobulin G infusion in women with recurrent spontaneous abortions.
AB  - PROBLEM: We investigated the hypothesis that elevated peripheral blood natural
      killer cells (NK) are decreased by immunoglobulin G infusion (IVIg) therapy in
      women with recurrent spontaneous abortions (RSA) and elevated NK cells. METHODS:
      Seventy-three women with RSA and elevated NK cells received IVIg therapy (400
      mg/Kg/day for 3 days ever 4 wks) and anticoagulation treatment. Peripheral blood
      immunophenotype assay by flow cytometry was done prospectively prior to and 7
      days after first IVIg therapy, every 2 wks until 20 wks gestation and then
      monthly. Controls were 95 women with RSA and normal NK cells who received
      anticoagulation treatment. RESULTS: (1) 86.3% of women with elevated NK cells who
      received the IVIg and anticoagulation therapy had a successful pregnancy outcome;
      (2) Peripheral blood CD56+ NK cells and CD56+/16+ NK cells were significantly
      suppressed 7 days post IVIg infusion (P < 0.0005); (3) Pre-IVIg infusion levels
      of other lymphocyte subsets were not different as compared with those of 7 days
      post-IVIg therapy; (4) Women who delivered a liveborn infant with IVIg therapy
      demonstrated downregulation of peripheral blood NK cells (CD56+, CD56+/16+)
      during early pregnancy when compared to women who miscarried the index pregnancy
      (P < 0.05); (5) Women with normal NK cells who miscarried while on
      anticoagulation therapy demonstrated significantly elevated CD56+ NK cells during
      early pregnancy as compared with that of women who delivered a liveborn infant (P
      < 0.05); (6) CD19+ B cells were significantly downregulated during pregnancy in
      women with anticoagulation and IVIg therapy when compared to women with
      anticoagulation therapy (P < 0.05). CONCLUSION: Downregulation of NK cells in
      women with RSA is associated with a favorable pregnancy outcome. Peripheral blood
      NK cells (CD56+, CD56+/16+) are effectively suppressed after IVIg therapy. Women
      with RSA and high NK cells benefit from IVIg therapy and experience suppression
      of CD56+ and CD56+/16+ NK cells.

PMID- 8739456
TI  - Intravenous immunoglobulin inhibits natural killer cell activity in vivo in women
      with recurrent spontaneous abortion.
AB  - We previously reported elevation of natural killer (NK) cells in women with
      recurrent spontaneous abortion (RSA) of immune etiology. In this study, we
      investigated the effect of intravenous immunoglobulin G (IVIg) on peripheral
      blood NK activity in vivo in women with RSA. Blood was drawn prior to and 7-11
      days after IVIg therapy in eight women with RSA. NK activity was measured using
      K562 as target cells for 51Cr-release assays. Serum IgG concentrations were also
      measured. All received 400 mg/kg/day of IVIg for 3 consecutive days. 1) Seven of
      eight women became pregnant. Five delivered a live born infant. Three out of five
      women (60%) who delivered a live born infant showed a significant inhibition of
      NK cytotoxicity post IVIg and the rest did not show any changes; 2) NK
      cytotoxicity was significantly increased in a woman who miscarried again; 3) A
      woman who miscarried a chromosomally abnormal fetus showed a significant
      inhibition of NK cytotoxicity after IVIg; and 4) Serum IgG concentration
      increased significantly from 9.3 +/- 3.0 mg/ml to 23.5 +/- 5.1 mg/ml post IVIg
      therapy. IVIg effectively inhibits peripheral blood NK activity in vivo. These
      results are consistent with our previous finding showing that IVIg inhibits NK
      cell activity in vitro. Women with RSA and elevated NK cells may benefit from
      IVIg treatment.

PMID- 8739457
TI  - Immunophenotypic profiles of peripheral blood lymphocytes in women with recurrent
      pregnancy losses and in infertile women with multiple failed in vitro
      fertilization cycles.
AB  - In summary (1) Nonpregnant women with RSAs of unknown etiology have higher levels
      of CD56+ lymphocytes when compared to normal controls; (2) The levels of CD19+,
      CD56+, and CD56+/CD16+ PBL of pregnant women with RSA are significantly higher
      than those of multiparous pregnant normal controls; (3) Women with autoantibodies
      to phospholipids have significantly higher levels of elevated CD56+ and
      CD56+/CD16+ lymphocytes when compared to women without antiphospholipid
      antibodies; (4) Women with autoantibodies to nuclear components demonstrate
      higher numbers of CD19+/CD5+ cells compared to women without autoantibodies to
      nuclear components; (5) Idiopathic infertile women with multiple prior IVF
      failures demonstrate significantly higher levels of CD56+ pBL than normal fertile
      controls and the conception rate is much higher in those with CD56+ levels less
      than 12%; (6) Elevations of CD56+ lymphocytes to over 18% during a pregnancy is a
      good prognostic indicator of impending pregnancy loss. We have not seen a
      liveborn infant in women with levels of 18% or higher without IVIg therapy; and
      (7) Infertile and RSA women who fail alloimmune and autoimmune therapy have
      significant alterations in cellular and humoral immunity involving NK cells and
      CD19+/CD5+ B cells.

PMID- 8739458
TI  - Embryotoxicity as a marker for recurrent pregnancy loss.
AB  - Some cases of unexplained recurrent pregnancy loss may be due to embryotoxic
      factors present in the mother's serum. In vitro assays have been devised to study
      the effect of these factors on pre-implantation, peri-implantation, and somite
      stage rodent embryos. Embryotoxic activity has been found in a high percentage of
      recurrent aborters but is also present in women with endometriosis and
      unexplained infertility, suggesting that there may be a range of factors acting
      at different stages of development. Embryotoxic activity may be predictive of
      pregnancy outcome and has been shown to be decreased after hormone and
      immunotherapy. However, its true value can only be assessed when the nature of
      the toxic factors is understood. Preliminary characterisation studies suggest
      that toxic activity may due to both immunological (antibodies or cytokines) and
      nutritional factors.

PMID- 8739459
TI  - Antiphospholipid antibody prevalence in patients with IVF failure.
AB  - Antiphospholipid antibodies (APAs) have been associated with reproductive
      wastage. The purpose of this study was to establish the prevalence of APAs in
      women who have had at least 12 embryos transferred during several in vitro
      fertilization (IVF) cycles without ensuing pregnancy. Sera from 42 women with IVF
      failure and 42 women who successfully conceived after IVF were tested for the
      presence of APAs by ELISA. Successful post-IVF pregnancy was determined by
      obtaining two consecutive rising beta-hCG levels followed by an ultrasound to
      confirm a viable conceptus. The sera were tested for three isotypes of antibody:
      IgA, IgG, and IgM against seven phospholipids: cardiolipin (CL),
      phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidic Acid (PA),
      phosphatidyl-glycerol (PG), phosphatidylcholine (PC), and phosphatidyl-serine
      (PS). From the IVF failure group, 11/42 (26.2%) were positive for APAs. From the
      control group, 2/42 (4.8%) were found positive only for IgA against PE. The
      difference between IVF failure and successful IVF groups was significant (P =
      0.01). These results suggest that antiphospholipid antibodies should be
      considered an important marker for increased risk of IVF failure. Patients who
      are involved with an IVF program should be tested for the presence of APAs prior
      to initiation of an IVF cycle.

PMID- 8739460
TI  - Antiphospholipid antibodies and recurrent pregnancy loss.

PMID- 8739461
TI  - A clinical trial for the treatment of antiphospholipid antibody-associated
      recurrent pregnancy loss with lower dose heparin and aspirin.
AB  - This study was conducted to determine if lower dose heparin (LD Heparin) combined
      with aspirin is as efficacious as higher dose heparin (HD Heparin) for the
      treatment of the antiphospholipid antibody syndrome in women seeking pregnancy.
      The method of the study was a prospective, single center trial including 50
      patients who were consecutively assigned to treatment. Each patient had at least
      three consecutive, spontaneous pregnancy losses, positive antiphospholipid
      antibodies on two occasions, and a complete evaluation. Data were compared using
      Fisher's exact test. Viable infants were delivered from 20/25 (80%) women treated
      with higher dose heparin vs. 19/25 (76%) of women treated with lower dose
      heparin. There were no significant differences between groups with respect to
      gestational age at the time of delivery (37.2 +/- 3.4 versus 37.7 +/- 1.6 weeks),
      maternal complications, or fetal complications. A lower dose of heparin plus
      aspirin was as effective as higher dose heparin for the treatment of
      antiphospholipid antibody-associated recurrent pregnancy loss.

PMID- 8739462
TI  - Impact of age on reproductive outcome in women with recurrent spontaneous
      abortions and infertility of immune etiology.
AB  - The objective of this paper is to determine whether age has any impact on
      conception rate, pregnancy outcome, or autoimmune status in women with recurrent
      spontaneous abortions (RSA) and infertility of immune etiology. One hundred
      twenty-four women with 3 or more RSA and 36 women with unexplained infertility
      were prospectively studied. Maternal antipaternal lymphocyte antibodies and
      autoantibodies to phospholipids and nuclear antigens were tested. All achieved an
      adequate alloimmune recognition after lymphocyte immunization and followed for 1
      year with optimal preconception autoimmune treatment. Conception rate and
      pregnancy outcome were prospectively studied. 1) 10.1% of women with RSA and
      30.6% of women with infertility failed to achieve a pregnancy after 1 year of
      trial (P = 0.0084); 2) in women with RSA, the number of previous fetal death
      after 28 weeks of gestation was significantly higher in women who failed to
      achieve a pregnancy within 1 year when compared to women who became pregnant (P =
      0.0296). Conception rate was not different with advancing age; 3) women with
      infertility demonstrated significantly higher incidence of anti
      phosphatidylethanolamine antibody when compared to women with RSA (P = 0.052); 4)
      in women with infertility, those who failed to achieve a pregnancy were
      significantly older (P = 0.0012) and demonstrated a higher incidence of
      autoantibodies to phosphatidic acid than women with infertility who became
      pregnant (P = 0.0339); 5) the subsequent spontaneous abortion rate while on
      optimal immune therapy was the same in the women with RSA (39.3%) and women with
      infertility (32%). Spontaneous abortion rate of women with RSA or infertility was
      not different among four age groups; 6) the presence of anticardiolipin antibody
      (P = 0.0055) and higher gravidity (P = 0.0354) correlated significantly with
      pregnancy failure in women with a history of infertility. The prevalence of auto
      antibodies to phospholipids and nuclear components was not different among four
      age groups in women with RSA or infertility. Age does not affect pregnancy
      outcome or conception rate in women with RSA. In women with infertility of immune
      etiology, conception rate was significantly reduced over age 40 although
      pregnancy outcome was no different with advanced age.

PMID- 8739463
TI  - Laboratory evaluation of women experiencing reproductive failure.
AB  - Reproductive life table analysis indicates that the majority of reproductive
      failures result from post fertilization failures, whether before or after
      implantation. It is important to have a set of tests to clarify the diagnosis of
      the reproductive failure so that appropriate therapy can be instituted. To
      determine the frequency of abnormal immunologic tests among women experiencing
      reproductive failure, 108 patients were evaluated for the presence of
      antiphospholipid antibodies (APA); lupus anticoagulant (LA); thyroid
      thyroglobulin and microsomal antibodies (TGT); embryotoxic factor (ETA); and
      systemic CD56+/CD16- cells. The frequency of abnormal results obtained from
      testing for APA, LA, TGT, ETA, and CD56+/CD16- cells among 108 patients with
      diagnoses of recurrent pregnancy loss (RPL)(n = 45), unexplained infertility (n =
      45) including IVF failure (n = 10), endometriosis (n = 10), premature ovarian
      failure (n = 5), and polycystic ovaries (n = 3) were compared with 15 normal
      controls. Seventy of one hundred eight (65%) women experiencing reproductive
      failure had at least one positive test, compared to 1 of 15 (7%) controls (P =
      0.0001). Presence of phospholipid antibodies was the most frequently abnormal
      result followed by elevated CD56+/CD 16 cells. The prevalence of a particular
      abnormal test varied among the diagnoses. The most frequent abnormal test among
      women with RPL was an increased percentage of CD56+/CD16- cells (40%), followed
      by APAs (29%), TGT (9%), and ETA (7%). The most frequent abnormal result among
      women with unexplained infertility was the presence of APAs (42%), followed by
      CD56+/CD16- cells (16%), ETA (16%), and TGT (9%). APA, CD56+/CD16- cells, ETA,
      and TGT are useful tools to assist in the diagnosis of reproductive failure.

PMID- 8739464
TI  - Neuroimmunological aspects of fetus and newborn brain damage in complicated
      pregnancy.
AB  - PROBLEM: The role of neuroautoimmune mechanisms in pathogenesis of perinatal
      damage of fetus and neonate brain during complicated pregnancy is considered to
      be important. METHOD: To determine neurospecific antigens (NSA) and their
      antibodies, ELISA and two-site column enzyme immunoassay were used. RESULTS: The
      contents of NSA and anti-brain antibodies, associated with fetal brain congenital
      development defects, account for the development of neuroautoimmune shifts in the
      mother-fetus system. The time of NSA appearance in serum from pregnant women, the
      dynamics of their level during pregnancy, and the appearance of anti-brain
      antibodies were determined, not by the nosology of extragenital pathology, but by
      the degree of fetus suffering, i.e., by the state of its central nervous system,
      connected with the decompensation of metabolic processes and homeostatic disorder
      in a mother-fetus system. CONCLUSIONS: Approved immunodiagnostic test systems
      should be recommended as markers for determination of pregnancy risk group,
      prognosticating perinatal pathology of neonatal and childhood CNS disorders.

PMID- 8739465
TI  - Cervical mucus anti-sperm antibodies: treatment with intrauterine insemination.
AB  - PROBLEM: To determine (1) the incidence of cervical mucus anti-sperm antibodies
      in infertile women, and (2) the results of treatment by intrauterine
      insemination. METHOD: Cervical mucus was collected the morning after urinary LH
      surge occurred from 153 consecutive women being treated for unexplained
      infertility with intrauterine insemination. Immunobead testing for IgG, IgA,
      IgA1, and IgA2 was performed with only actively motile sperm being counted.
      RESULTS: Overall, 23/153 (15.0%) of cervical mucus samples were positive for anti
      sperm antibodies: 9/23 (39.1%) were only IgA-positive (62% IgA1-positive, 38%
      IgA2-positive), 11/23 (47.8%) were only IgG-positive, and 3/23 (13.0%) were
      positive for both IgA and IgG. Insemination resulted in a pregnancy in 6/23
      (26.1%) of women with cervical mucus anti-sperm antibodies after 1-3 cycles.
      CONCLUSIONS: Testing for cervical mucus anti-sperm antibodies should be performed
      in cases of "unexplained" infertility, and intrauterine insemination may be an
      effective treatment, resulting in pregnancies in over one-fourth of couples.

PMID- 8739466
TI  - Comparative evaluation of p53-protein expression and the PCNA and Ki-67
      proliferating cell indices in human astrocytomas.
AB  - Mutations of the p53 gene are one of the most frequent genomic alterations of
      human tumours of astrocytic lineage. Because the physiological role of this gene
      is a suppression of cellular proliferation and growth, the overexpression of p53
      protein may correlate with the expression of PCNA or Ki-67, established markers
      of cell proliferation. Paraffin-embedded surgical specimens from 60 human
      astrocytomas (9 pilocytic tumours, 12 WHO grade II, 9 anaplastic astrocytomas
      [WHO grade III] and 30 glioblastomas [WHO grade IV]) were stained with anti-PCNA
      (PC10), anti-p53(DO-7) and anti-Ki-67 antibodies (DAKO). Approximately 40% of all
      the cases were p53-protein immunopositive (53.3% glioblastomas, 33.3% anaplastic,
      41.7% low grade astrocytomas but no pilocytic tumor). Statistical analysis did
      not reveal statistically significant correlation between p53-immunopositivity and
      PCNA or Ki-67 labeling indices. The Ki-67- and PCNA LI-s were statistically
      correlated, and the former better discriminated groups of different grades of
      malignancy.

PMID- 8739467
TI  - Morphologic differences between latent membrane protein-1 (LMP-1)-positive and
      negative tumour cells in Epstein-Barr virus (EBV)-related childhood Hodgkin's
      disease. A morphometric study.
AB  - The values of five cellular morphometric parameters (longest and shortest
      cytoplasmic axis, cellular circumference, area and roundness coefficient) were
      compared between 20 Latent Membrane Protein 1 (LMP-1)-positive and an equal
      number of LMP-1-negative Reed-Sternberg and Hodgkin (HRS) cells for each of 13
      cases of Hodgkin's disease (HD) occurring in children (aged 3-15 years); the
      presence of Epstein-Barr virus (EBV) encoded EBER mRNAs had previously been
      detected in all cases using RNA in situ hybridisation (RISH), while the presence
      of LMP-1 was immunohistochemically detected using the alkaline phosphatase
      antialkaline phosphatase (APAAP) method. The longest and shortest axis,
      circumference and area were larger in LMP-1-positive than in LMP-1 negative HRS
      cells, while the roundness coefficient of LMP-positive HRS cells was smaller than
      that of LMP-1 negative cells. All differences were statistically highly
      significant when univariate (paired comparisons) t-test were used. Multivariate
      analysis (Hotelling's T2 test) showed all differences (except the roundness
      coefficient) to be significant both at the 5% and 1% level of significance. These
      results provide a numerical basis for the alteration brought by the expression of
      LMP-1 in the cellular skeleton of tumour (HRS) cells in EBV-related childhood HD
      cases.

PMID- 8739468
TI  - Immunohistological detection of estrogen and progesterone receptors in multiple
      and well differentiated leiomyomatous lung tumors in women with uterine
      leiomyomas (so-called benign metastasizing leiomyomas). A report on 5 cases.
AB  - Seventy-four cases of so-called "benign metastasizing uterine leiomyomata" are
      reported in the literature. In these cases, well differentiated, leiomyomatous
      lung tumors developed, usually after a period of several years. Histologically,
      these tumors appear to be benign. We report on five more such cases in which we
      investigated the contents of estrogen and progesterone receptors in the pulmonary
      tumors by immunohistological procedures. All the lung tumors exhibited a high
      content of progesterone receptors, and in 4 out of the 5 cases a high estrogen
      receptor content was also found. Modern immunohistological techniques permit the
      investigation of routinely fixed tissue blocks, and it is thus recommended that
      the contents of these hormone receptors should be determined in well
      differentiated, leiomyomatous lung tumors from women. This would both provide
      information on the pathogenesis of these tumors and establish a basis for
      possible later institution of hormone treatment. It is likely that the majority
      of these lung tumors are in fact metastases of extremely well differentiated
      leiomyosarcomas of the uterus. The possibility that lung tumors of this type may
      constitute a small group that develop in situ as hormone-sensitive proliferations
      cannot, however, be fully excluded.

PMID- 8739469
TI  - The localization of tissue factor and apolipoprotein(a) in atherosclerotic
      lesions of the human aorta and their relation to fibrinogen-fibrin transition.
AB  - We examined the immunohistochemical distribution of tissue factor (TF),
      apolipoprotein (a) (apo(a)) in atherosclerotic intimas of human thoracic aortas
      obtained from 51 autopsies in order to analyze the mechanism of fibrinogen-fibrin
      transition as a part of thrombogenic properties of atherosclerotic intimas. TF
      was overexpressed mainly by macrophages in both fatty streaks and more advanced
      lesions, while it was also scatteringly deposited in the matrix of advanced
      lesions, especially in the atheromatous gruel. TF-positive macrophages were
      frequently intermingled at the base of fibrin thrombi formed on the eroded
      intimas. On the other hand, apo(a) was localized in the stroma and within some
      macrophages, and also in the mural thrombi. Fibrinogen and fibrin were more
      frequently detected in the matrix of advanced lesions than in that of early
      lesions. Fibrin was occasionally co-located with cell- and matrix-associated TF
      and apo(a) deposited in matrix. These findings suggest that the overexpressed TF
      in the atherosclerotic intima plays a critical role in the initiation of fibrin
      formation. This could result from either fibrinogen permeating into the intima or
      from rupture of the fibrous cap overlying atheromas. Apo(a) deposited in the
      atherosclerotic intima may also participate in the persistent deposition of
      fibrin.

PMID- 8739470
TI  - Immunohistochemical labelling for prostate specific antigen in non-prostatic
      tissues.
AB  - Immunohistochemical detection of prostate specific antigen (PSA) in metastases of
      adenocarcinomas is widely used as an aid to identify the prostatic origin of
      metastatic cells. However, on the one hand, PSA may not be expressed in some
      poorly differentiated prostatic carcinomas, while on the other, PSA
      immunoreactivity has been found in small amounts in non-prostatic tissues. The
      aim of the current study was to evaluate the prevalence of PSA immunoreactivity
      in normal non-prostatic tissues and in breast carcinoma. PSA was localized by
      immunohistochemistry with four commercial antibodies in 34 different normal human
      tissues, and in 15 ductal and seven apocrine breast carcinomas. Concentrations of
      PSA in tissue homogenates of prostate and nine non-prostatic tissues from
      autopsied subjects were measured by a two-site immunoradiometric assay. Weak PSA
      immunoreactivity was found by immunohistochemistry in kidney, parotid gland and
      pancreatic tissues. Variable PSA immunoreactivity was seen in three cases of
      ductal (20%) and two cases of apocrine breast carcinoma (28%). No consistent PSA
      immunoreactivity was found in homogenates of non-prostatic tissues by the
      immunoradiometric assay. We conclude that PSA is a quite specific marker of
      prostatic tissue. However, there are some non-prostatic neoplastic and normal
      tissues that express PSA. Therefore, a definite diagnosis of metastasis of
      prostatic origin cannot be made on the basis of immunolabelling for PSA alone.

PMID- 8739471
TI  - Variability of airway structure and inflammation in normal subjects and in cases
      of nonfatal and fatal asthma.
AB  - The quantitative assessment of airway inflammation in patients with apparently
      similar clinical severity of asthma has yielded variable results. The aim of this
      study was to assess the variability of inflammatory cell counts and airway
      structure in large and small airways from subjects with and without asthma, and
      to calculate the number of cases required to detect significant differences
      between disease groups. Three serial transverse sections, 20 microns apart, were
      examined from cartilaginous and membranous bronchioles. Airway dimensions
      measured were the areas and perimeters defined by the luminal surface of the
      airway epithelium, basement membrane, outer border of airway smooth muscle, and
      surrounding border of the airway adventitia. Airway wall components measured were
      the areas of airway smooth muscle, mucous glands and cartilage. The numbers (per
      mm of basement membrane) of lymphocytes, eosinophils, neutrophils and plasma
      cells were counted using haematoxylin and eosin staining and mast cells were
      counted in sections stained with Toluidine blue. Measurements were repeated by
      two or three observers. The coefficient of variation (CV) was used to assess
      intraairway, intraobserver and interobserver variability. For airway dimensions
      the mean (+/- SD) CV within airways was 3.8% +/- 2.1%, within observers was 3.7%
      +/- 1.8% and between observers, 3.4% +/- 1.8%. For airway wall components, the CV
      within airways was 10.7% +/- 4.6%, and between observers was 8.8% +/- 2.2%. For
      cell counts, the CV within airways was 20.8% +/- 12.5%, within observers was 8.3%
      +/- 3.7% and between observers, 9.6% +/- 4.6%. There were no significant
      differences in variability between cases with and without asthma. Intra-airway
      variability was higher (p < 0.05) in membranous airways (5.6% +/- 1.7%) than in
      large cartilaginous airways (2.3% +/- 1.1%). We estimate that between 5 and 15
      cases in each group would be required to detect differences of 50-100% between
      groups, depending on the parameter being compared. These findings suggest that
      airway structure and inflammatory cell numbers are uniform throughout the
      bronchial tree in normal and asthmatic cases, and that small samples of large or
      small airways are likely to be representative when comparing cases.

PMID- 8739472
TI  - Intracellular protozoan infection in small intestinal biopsies of patients with
      AIDS. Light and electron microscopic evaluation.
AB  - Small intestinal biopsies of 21 patients with acquired immunodeficiency syndrome
      (AIDS) with light microscopic findings diagnostic or suspicious for parasite
      infection were investigated by transmission electron microscopy (TEM). TEM
      allowed us to identify and specify the genus and species of involved parasites in
      16 out of the 21 cases: 7 Cryptosporidium parvum, 5 Enterocytozoon bieneusi and 4
      Isospora belli. Cryptosporidium was easily identified on light microscopy (LM),
      and only slightly influenced by parasite burden in all the 7 cases; TEM confirmed
      LM diagnosis and made it possible to characterize the parasites as C. parvum. The
      identification of Microsporidium on LM in our cases was related to the burden of
      parasite; its presence was certainty identified in 2 cases and suspected in 3.
      TEM allowed to identify these parasites as E. bieneusi. Intracytoplasmic coccidia
      could be detected with certainly in semithin sections in all 4 cases, but TEM was
      always needed to specify the infectious agent as I. belli. In 5 cases the
      suspicious of protozoan infection on LM (3 microsporidia, 1 intracytoplasmic
      coccidia and 1 Cryptosporidium) was not confirmed by TEM. Our data suggest that
      TEM is an appropriate diagnostic tool in this field of pathology and necessary in
      most of the cases.

PMID- 8739473
TI  - Activation of microglia in haemorrhage microzones in human embryonic cortex. An
      ultrastructural description.
AB  - We have noted the presence within parietal cortex of microzones of haemorrhage in
      two 14 week gestation fetuses. These were obtained from mothers with no clinical
      history indicative of infection or other pathological developmental data. The
      microzones of haemorrhage were complicated by degenerative changes in adjacent
      neurones and activation of putative microglial cells while other surrounding
      regions of developing cortex showed no signs of destructive alterations. This
      indicates that these zones are not simply the result of the termination
      procedure. Microglia associated with these haemorrhagic microzones showed
      increased vacuolization, phagocytic activity and abundant phagosomes. Although
      the cause of the microzones of haemorrhage is unknown, these observations are of
      interest since they are the first demonstration of possible activation of
      microglia in such an early stage of human development. This finding suggests that
      the presence of microhaemorrhage and associated neuronal death may provide an
      inducible stimulus of microglial cells during early brain development, even
      before programmed neuronal death occurs.

PMID- 8739474
TI  - Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH)-syndrome.
      Ultrastructural changes of mitochondria in cultured dermal fibroblasts of three
      patients.
AB  - Mitochondria of fibroblasts cultured from the skin obtained at biopsy from three
      patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH)
      syndrome, one of the autosomal recessive, heritable urea cycle disorders, were
      studied with appropriate controls ultrastructurally. The patients were two
      severely retarded 10- and 12-year-old boys, and a 22-year-old sister of the
      former whose mental status was at the low normal range; she never had motor
      impairments or seizures. The mitochondria, similar in all three patients, were
      increased in number, very long, branching and/or "looping," and tortuous. "Spurs"
      or "buddings" extended from their lateral surfaces and the terminal segments were
      often bulbous. Other unusual configurations were also present. In addition, giant
      forms with large diameter contained innumerable closely-packed and parallel
      cristae which traversed the entire width of these mitochondria; at times they
      assumed a "whirled" pattern. The mitochondrial matrix was usually of high
      electron density. These changes were not a feature of fibroblastic mitochondria
      of controls. Several changes resembled those of hepatic mitochondria in this
      disorder. All features are interpreted as an attempt at expanding the
      mitochondrial volume (via structural substratum) to compensate for the metabolic
      incompetence of these organelles (a block in transmembranous transfer of
      ornithine from hyaloplasm into mitochondria for conversion to citrulline).

PMID- 8739475
TI  - Immunohistochemical detection of 1,25-dihydroxyvitamin D3 receptors (VDR) in
      human skin. A comparison of five antibodies.
AB  - Increasing evidence suggests an important regulatory function for 1 alpha,25
      dihydroxyvitamin D3 in the growth control of epidermal cells and in skin
      immunology. Using immunohistochemical techniques we investigated the in situ
      expression of 1,25-dihydroxyvitamin D3 receptors (VDR) in normal human skin with
      one monoclonal rat antibody and four monospecific polyclonal rat antibodies to
      the VDR. Polyclonal rabbit antibodies have been raised against synthetic peptides
      corresponding to different amino acid residues of the human VDR, including
      regions close to the DNA binding domain and the hormone-binding domain. All
      antibodies revealed positive immunoreactivity in normal human skin. The
      antibodies showed differences in subcellular immunoreactivity and staining
      intensity. Differences in subcellular distribution of VDR immunoreactivity are
      caused by the different epitopes recognized by the antibodies and not by the
      affinity of the antibodies for VDR. It seems that the antibodies may recognize
      different functional modifications of the receptor molecule (i.e.: hormone bound
      vs. hormone free; DNA bound vs. non-DNA bound; VDR vs. VDR/retinoid-X receptor
      [RXR] heterodimers). Using these newly raised antibodies future studies will be
      carried out to analyse subcellular distribution of VDR immunoreactivity in skin
      pathology.

PMID- 8739476
TI  - Pulmonary capillary hemangiomatosis as a rare cause of pulmonary hypertension.
AB  - Pulmonary capillary hemangiomatosis (PCH), first described by Wagenvoort et al.
      in 1978, is a rare cause of pulmonary hypertension which occurs predominantly in
      young adults. In the literature only 18 cases have been reported. In 1988
      Langleben et al. proposed a hereditary form of PCH with probable autosomal
      recessive transmission. Histologic findings include irregular small nodular foci
      of thin-walled capillary-sized vessels which diffusely invade the lung
      parenchyma, the bronchial/bronchiolar walls and the adventitia of large vessels.
      We report on a case of PCH in a 24 year old man who presented the clinical signs
      of interstitial lung disease.

PMID- 8739477
TI  - Cystic endometriosis of the upper abdominal organs. Report on three cases and
      review of the literature.
AB  - A 34-year-old woman with signs and symptoms of an acute abdomen was found to have
      a hepatic cyst on NMR- and CT-scan. With the tentative diagnosis of a liver
      hematoma, a right hemihepatectomy was performed. Histologically, an endometrial
      cyst of the liver was found. A second case of cystic endometriosis in the liver
      was revealed ultrasonographically in a 62-year-old woman, complaining of
      rightsided epigastrical pain. A 28-year-old woman was admitted to the hospital
      because of recurrent epigastric pain. A cystic tumor of the pancreas could be
      visualized ultrasonographically and was interpreted as a postinflammatory
      pseudocyst. Histological examination of the distal pancreatectomy specimen
      revealed cystic endometriosis. The clinicopathological features of hepatic and
      pancreatic endometriosis are discussed and the literature concerning these
      extremely rare lesions is reviewed.

PMID- 8739478
TI  - Necrotizing sarcoid granulomatosis with and without extrapulmonary involvement.
AB  - Three cases of necrotizing sarcoid granulomatosis (NSG) are reported. All 3
      patients had pulmonary lesions; one of them had additional extrapulmonary lesions
      which were ophthalmologic (dacryoadenitis) and digestive (ulcerative colitis).
      This patient was followed for 5 years and developed several respiratory,
      ophthalmologic and digestive recurrences. In 2 cases the diagnosis of NSG had
      been initially overlooked and the authors emphasize the difficulties of this
      histologic diagnosis in terms of the differential diagnosis with other necrotic
      and granulomatous pulmonary diseases such as tuberculosis and Wegener's
      granulomatosis. They stress the possibility of extrapulmonary lesions in NSG and
      discuss the relationship between NSG and sarcoidosis.

PMID- 8739479
TI  - Bronchial allergen challenge methodological studies.

PMID- 8739480
TI  - Lung function testing: the dilemma of predicted values in relation to the
      individual variability.
AB  - Quantitated lung function parameters are usually interpreted in relation to so
      called "normal ranges' obtained from healthy study groups. The aim of this paper
      is the critical review of formulas and the evaluation of intraindividual
      variation in modern lung function testing. To which extent is the total variation
      of lung function parameters in cross-sectional studies (usually serving as basis
      for the normal range) attributed to the intraindividual variation between
      repeated measurements? This question raises a further question: are lung function
      values in the normal range really normal? To assess spirometric and body
      plethysmographic parameters 26 healthy subjects from three medical centers
      underwent 30-72 measurements over a period of 2 months for the determination of
      variations due to (1) intraindividual variation over time and (2) interindividual
      variation. For each subject, predicted values of different lung function
      parameters published by Quanjer et al. [Eur Respir J 1993; 6:5-40.1], of
      intrathoracic gas volume by Ulmer et al. [Die Lungenfunktion; Stuttgart, Thieme,
      1991] and of total airway resistance by Ruehle and Matthys [Pneumologie
      1976;153:223] were applied. When converted into percent predicted and adjusted
      for differences in medical centers, the intraindividual standard deviation was
      estimated to be about half of the interindividual standard deviation. We conclude
      that the normal range of lung function parameters derived from the standard
      deviation within populations is too wide for the assessment of individual values.
      Interpretation of individual lung function measurements should primarily be based
      on the "individual normal range' derived from former lung function measurements
      of the individual and only secondly on the "predicted value'.

PMID- 8739481
TI  - Analysis of variability in interpretation of spirometric tests.
AB  - The objective of this study was to quantify the degree of disagreement in
      interpretation of spirometries and in the definition of the airway obstruction
      and response to bronchodilators (Bd) in different publications. Two surveys were
      carried out in which two groups of 15 pulmonologists were asked to identify in
      several spirometries the presence and degree of obstructive or restrictive
      defects (OD or RD), the response to Bd and whether the test was assessable or
      not. Three "problem' spirograms (PS) were included. For RD there was 76.1% of
      maximum agreement (MA). For OD the MA was 63.6%. Of the PS only 14% of the tests
      with a higher than 40% variation among the curves, 14% of those which did not
      include the graphic records and 33% of those with a considerably imperfect curve
      were considered nonassessable. The degree of disagreement for response to Bd was
      24% (this implies 53.3% of possible maximal disagreement). Besides, every
      original article whose title or summary referred to "asthma', "chronic
      obstructive lung disease' or "chronic airflow obstruction' which was published
      from July 1991 to July 1993 in two respiratory medical journals (Chest and
      Thorax) was examined. Eleven different criteria to define obstruction were found.
      The most frequently used was FEV1/FVC < 70% (33.3%). Five different definitions
      of a positive response to Bd were found. The most popular was an increase in FEV1
      > 15% of the initial value (76%). We conclude that there is very often
      disagreement in the interpretation of conventional spirometry. The definition of
      obstruction and reversibility in clinical trials is not uniform and great care
      must be taken when extrapolating the results from one publication to another
      since the composition of its samples could be substantially different.

PMID- 8739482
TI  - Effects of willful ventilatory control on respiratory sensation during
      hypercapnia.
AB  - Remarkable augmentation of breathing discomfort has been noted when ventilation
      is constrained to the steady state level during progressive hypercapnia. However,
      the effect of willful enhancement of ventilation on breathing discomfort remains
      to be evaluated. The present study examined the effects of moderate willful
      increases or decreases in ventilation during progressive hypercapnia on breathing
      discomfort in 12 subjects. There were a total of 5 rebreathing trials. In the
      first (F1) and the fifth trials the subjects rebreathed freely. In the other
      trials subjects breathed by tracking a target to achieve hypercapnic ventilatory
      responses that were the same (HCVR-S), 25% higher (HCVR-H) and 25% lower (HCVR-L)
      than in the F1 trial. Breathing discomfort was assessed every 30 s by a 150-mm
      visual analog scale (VAS). The sensational response (dVAS/dPCO2) during HCVR-S
      [3.8 +/- (SE) 0.8 mm/Torr] was significantly smaller (p < 0.01) than that during
      the F1 (6.3 +/- 0.8 mm/Torr) trial. HCVR-H resulted in a further decrease in
      dVAS/dPCO2 to 3.1 +/- 0.7 mm/Torr as compared to HCVR-S (p < 0.05). HCVR-L
      significantly increased dVAS/dPCO2 to 4.9 +/- 0.7 mm/Torr compared to HCVR-S (p <
      0.05). The final free rebreathing ventilatory response was significantly larger
      than the initial free rebreathing response (2.7 +/- 0.5 as compared to 2.1 +/-
      0.4 liters/min/Torr, p < 0.01). However, the sensational response did not change
      (6.3 +/- 0.8 vs. 5.8 +/- 0.7 mm/Torr). These rebreathing studies indicate that
      willful control of respiration decreases respiratory sensation even at comparable
      levels of ventilation. In particular, moderate willful increases in ventilation
      produce an ameliorating effect on the sensation of breathing discomfort.

PMID- 8739483
TI  - Restoration of lung compliance with calf lung surfactant extract and a surfactant
      analog in an in situ model of surfactant deficiency in rats.
AB  - We have developed a standardized in situ lung surfactant deficiency model in the
      rat by using a single bronchoalveolar lavage (BAL). The purpose of this study was
      to assess the usefulness of surfactants and surfactant analogs in terms of their
      in vivo physiological properties. Calf lung surfactant extract (CLSE) was shown
      to improve lung compliance in a dose-dependent manner in this surfactant
      deficiency model when administered intratracheally immediately after BAL. In
      addition, CLSE formulated with a diether (palmityl) phosphonolipid surfactant
      analog significantly improved the compliance post-BAL as compared to CLSE alone.
      We propose that this in situ bioassay may be useful for the assessment of
      physiological capabilities of surfactants, surfactant analogs and surfactant
      formulations.

PMID- 8739484
TI  - Comparison of the effect of a high and low dose of atropin on the ultrastructure
      of the tracheal epithelium.
AB  - The ultrastructure of rabbit tracheal epithelium was studied 20 min after
      injection of 0.04 and 0.5 mg of atropin. The tracheae were lined with altered
      ciliated pseudostratified columnar epithelium. The degree of damage to the
      epithelial cells was dose dependent. The injury to the tracheal epithelium due to
      treatment with 0.04 mg of atropin was considered mild. The administration of the
      higher dose of atropin caused moderately severe epithelial damage. Both
      experimental groups exhibited morphological signs of impaired self-cleaning
      ability.

PMID- 8739485
TI  - Long-term lung sequelae following accidental chlorine gas exposure.
AB  - Acute exposure to sublethal doses of chlorine gas resulted in persistent
      pulmonary symptoms in 3 patients who had no past history of respiratory disease.
      The patients complained of intermittent dyspnea in association with respiratory
      irritants and physical exertion for more than 2.5 years postexposure. Four months
      after the accident bronchoalveolar lavage showed an inflammatory cell reaction,
      whereas 16 months later the differential cytology proved nearly normal. Moderate
      to severe nonspecific bronchial hyperresponsiveness was assessed in intervals of
      4, 20 and 30 months after the accident. All patients showed the typical features
      of the reactive airways dysfunction syndrome defined as an asthma-like
      occupational illness after an acute exposure to highly concentrated respiratory
      irritants. We conclude that a single high exposure to chlorine gas may lead both
      to acute respiratory injury and to long-term reactive airway dysfunction with
      typical symptoms of inflammatory changes of the airways and nonspecific bronchial
      hyperresponsiveness.

PMID- 8739486
TI  - Sarcoidosis: chest radiograph screening of familial contacts.
AB  - On the basis of the hypothesis that sarcoidosis might be a transmissible disease,
      we thought a study of the familial contacts of known cases, as is done in
      tuberculosis, might reveal asymptomatic cases. In order to assess the efficiency
      of chest radiographs in detecting asymptomatic sarcoidosis in such contacts, we
      carried out a cross-sectional study. The population studied consisted of 66 index
      cases of sarcoidosis who were self-selected by their agreeing to take part in the
      study. Criteria were established with regard to the size of the family to be
      studied, along with three grades of intensity in the relationship between the
      index cases and their respective contacts. 976 familial contacts over 14 years of
      age, from grandparents to grandchildren of the index cases were identified,
      including nonconsanguineous contacts. 496 close contacts were asked to take part
      in the survey. Among these contacts there were 2 with a previous sarcoidosis, a
      prevalence of 4/1,000. 239 of these 496 contacts agreed to radiograph screening.
      Among those screened, no new cases of sarcoidosis were detected. We concluded
      that at present in our environment, with a low incidence and good prognosis,
      routine screening of relatives is not indicated. Nevertheless, longitudinal
      epidemiological studies designed to ascertain the pattern of transmission of the
      disease and including chest radiograph screening in a population with a high
      incidence of the disease could be of interest.

PMID- 8739487
TI  - Value of routine microbial investigation in community-acquired pneumonia treated
      in a tertiary care center.
AB  - The study was conducted at a tertiary care and teaching hospital with about 200
      beds for internal medicine. The objective was to determine the diagnostic yield
      and value in directing antibiotic therapy of a routine microbial approach in
      patients with community-acquired pneumonia referred to a tertiary care center. We
      studied 93 episodes in a retrospective study. 69/93 (74%) cases were treated with
      at least one empirical antibiotic therapy prior to admission. Microbial
      investigation was performed in 83/93 cases (89%). An etiological agent was
      established in 19/83 (23%) cases including 7/50 (14%) by blood culture and 12/52
      (23%) by serology. Bronchoscopy with 18 protected specimen brush and 20
      bronchoalveolar lavage examinations was definitely diagnostic in only 1/25 (4%)
      cases, and this case was also identified by blood culture. 5/25 (20%) were
      probably diagnostic. Three pathogens, Streptococcus pneumoniae, Mycoplasma
      pneumoniae and Legionella pneumophila, accounted for 15/19 (79%) of the
      identified agents. The diagnostic results directed a change in antibiotic therapy
      in 6/19 (32%) of cases with definitely proven pathogens. 4/19 (21%) of cases
      would have been treated with an inappropriate regimen without diagnostic results.
      The diagnostic yield of routine microbial investigation in pretreated patients is
      low. The routine approach reveals its limited value especially in patients with
      severe courses. The role of bronchoscopy remains to be defined for patients with
      severe (and pretreated) community-acquired pneumonia.

PMID- 8739488
TI  - The effect of diabetes mellitus on the outcome of patients with chronic
      obstructive pulmonary disease exacerbated due to respiratory infections.
AB  - During the last 2 years, 597 cases of chronic obstructive pulmonary disease
      (COPD) exacerbated due to respiratory infections were treated in our department.
      Eighty-eight (14.7%) of them suffered from diabetes mellitus (DM). Thirty-four
      had insulin-dependent DM and 54 non-insulin-dependent DM. In these groups, we
      studied the duration of hospitalization, their clinical features, chest X-rays,
      blood tests (white blood cells, erythrocyte sedimentation rate), blood gases and
      the sputum culture for bacteria. The paired t test was used for statistical
      analysis. Our results showed that the mean duration of hospitalization in
      patients with DM was 10.76 +/- 2.7 days (X +/- SD), whereas for patients without
      DM it was 8.53 +/- 1.9 days. Patients with insulin-dependent DM had a mean
      hospitalization of 15.63 +/- 3.6 days, which was statistically significant in
      relation to the group without DM (p < 0.0001). As for the chest X-rays, clinical
      features, blood tests and blood gases, no statistically significant differences
      were found among the groups. The sputum culture for bacteria showed that in
      patients with insulin-dependent DM the isolation of gram-negative bacteria was
      51.6%, which was statistically significant in relation to the group without DM,
      where it was 27.3% (p < 0.0001). In conclusion, a significant percentage of
      patients with COPD suffers from DM. Patients with insulin-dependent DM and COPD
      with respiratory infections were found to have longer periods of hospitalization
      and a larger percentage of gram-negative bacteria in the sputum culture.

PMID- 8739489
TI  - Prevention of acute exacerbations of chronic obstructive bronchitis with
      carbocysteine lysine salt monohydrate: a multicenter, double-blind, placebo
      controlled trial.
AB  - The efficacy and safety of carbocysteine lysine salt monohydrate (SCMC-Lys) in
      the prevention of acute exacerbations associated with chronic obstructive
      bronchitis were evaluated in a multicenter double-blind, placebo-controlled,
      parallel group trial in 662 outpatients. After a 1-month run-in period, patients
      were randomized to three groups and assigned to receive one of the following oral
      treatments: continuous SCMC-Lys 2.7 g once daily, intermittent SCMC-Lys at the
      same dosage (1-week courses alternating with 1-week intervals on placebo) or
      placebo. Each treatment lasted for 6 months and spanned the cooler months of the
      year. Evaluation was based on a daily recording of relevant clinical symptoms and
      signs and subsequent evaluation of the collected data by three blinded
      independent physicians. A total of 146 patients (23%) failed to complete the 6
      month treatment (mostly due to difficulties in complying with protocol
      requirements), without clear-cut differences in the dropout rate in the three
      groups. An intention-to-treat analysis revealed that the incidence of patients
      without exacerbations in the group assigned to continuous SCMC-Lys treatment was
      significantly higher than in the placebo-treated group (p < 0.001). The total
      number of patients with at least one exacerbation was 66 (29.6%) in the group
      treated with continuous SCMC-Lys compared with 100 (45.9%) with placebo. In the
      former group the time between initiation of treatment and first exacerbation was
      significantly prolonged. The average number of days with acute respiratory
      illness was significantly decreased in the group receiving continuous SCMC-Lys
      compared with the group receiving placebo, and this was associated with a
      significant reduction in the antibiotic consumption during the trial period. In
      patients assigned to intermittent treatment, results of the assessed endpoints
      did not differ significantly from those observed in the placebo group. No serious
      adverse effects were reported. It is concluded that continuous administration of
      SCMC-Lys throughout the winter season is effective in preventing acute
      exacerbations in patients with chronic obstructive bronchitis and it is well
      tolerated.

PMID- 8739490
TI  - Computer-tomographically guided fiberbronchoscopic transbronchial biopsy of small
      pulmonary lesions: a feasibility study.
AB  - Small pulmonary lesions localized in peripheral airways or lung parenchyma are
      mostly not visible by means of flexible or rigid bronchoscopy for they are distal
      to the inspectable airway caliber. Therefore fluoroscopy is necessary to direct
      the flexible biopsy forceps or biopsy needle to the lesion. Even a two
      dimensional fluoroscopic guidance does not guarantee an access to the focus.
      Therefore we investigated a method to overcome these problems. In 9 patients with
      peripheral lung lesions where the conventional method had failed to provide
      sufficient biopsies CT-guided bronchoscopy was done. Central airways were
      carefully inspected, and the flexible forceps was introduced into the bronchial
      branch leading to the focus under fluoroscopic control. Then the forceps was
      localized in the axial plane by CT and guided directly to the lesion.
      Subsequently the forceps was opened and contact to the lesion was confirmed by CT
      scan before the biopsies were taken. Thus the three-dimensional control of the
      position of the forceps made it possible to get biopsies directly from the region
      of interest. The method provides the possibility of reaching even small
      peripheral lesions that have been missed by the conventional techniques, thereby,
      although technically more difficult for the examiner, providing a smaller risk of
      complications and no additional discomfort for the patient.

PMID- 8739491
TI  - Bilateral diaphragmatic paralysis after mediastinal radiotherapy.
AB  - A 35-year-old man presented bilateral phrenic paralysis 7 months after radio
      therapy for treatment of Hodgkin's lymphoma. Diaphragmatic dysfunction appeared
      after complete lymphoma remission and 4 months after chemotherapy
      discontinuation. There were no other potential causes. Idiopathic diaphragmatic
      paralysis was unlikely because it is usually unilateral. Radiation-induced
      neuropathy is well documented in other nerves as the brachial plexus. The timing,
      the applied dose and the location of the nerve within the radiation field are
      suggestive of radiation-induced phrenic nerve damage. Partial recovery was
      achieved after 4 years' follow-up.

PMID- 8739492
TI  - Sleeve superior segmentectomy of the right lower lobe for endobronchial
      neurinoma. Report of a case.
AB  - A 30-year-old woman was found to have an obstructive intrapulmonary tumor at the
      right intermediate bronchus which caused atelectases of both right middle and
      lower lobes. The diagnosis of endobronchial neurinoma was made by
      bronchofiberscopic biopsy. Since the tumor was benign, we considered an operative
      procedure which would enable both complete resection of the tumor and
      preservation of the pulmonary function. By utilizing the techniques of sleeve
      superior segmentectomy of the right lower lobe and telescoping bronchial
      anastomosis, both objectives were achieved.

PMID- 8739494
TI  - Necrosis and apoptosis in neuroretina and pigment epithelium after diffuse
      photodynamic action in rats: a light and electron microscopic study.
AB  - Cell death in the rat retina has been shown to occur mainly along two distinct
      pathways after pressure-induced ischemia. The authors conducted a qualitative
      investigation to determine whether similar types of cell death could be
      identified after diffuse photodynamic injury and photothrombosis. After i.v.
      injection of rose bengal (40 mg/kg), the eyes of 21 albino rats were exposed to
      light for durations ranging from 2 to 15 minutes, at a light intensity of 15
      17,000 ft-cd, with interposition of a Kodak Wratten gelatin filter #15. Survival
      times ranged from 15 minutes to 6 days. The specimens were studied by light and
      electron microscopy. We identified two types of retinal cell death in the
      neuroretina and in the retinal pigment epithelium (RPE). Type I cell death was
      consistent with necrosis, and type-II cell death showed many features of
      apoptosis. These observations may not be exhaustive. The patterns of retinal cell
      death in this model appeared to be identical with those found after pressure
      induced ischemia. The morphology of apoptosis of the RPE is hitherto undescribed.
      This study corroborates the concept of a limited number of types of cell death in
      the retina after exposure to noxious stimuli of various kinds.

PMID- 8739493
TI  - Behet's syndrome with pulmonary involvement-combined therapy for endobronchial
      stenosis using neodym-YAG laser, balloon dilation and immunosuppression.
AB  - We present a case report of a patient suffering from Behet's syndrome with
      pulmonary involvement. The development of endobronchial granulomatosis in the
      bronchus intermedius and right upper lobe bronchus led to severe bronchial
      stenosis and dyspnoea. Also aphthous ulcerations in the bronchial mucosa
      occurred. Treatment of the granulomatous stenosis consisted of Neodym-YAG laser
      resection and immunosuppression. On follow-up there was a recurrence of the
      stenosis, characterised by fibrotic strictures. Therefore a balloon dilation was
      performed and immunosuppression instituted, which led to an increase in airway
      diameter and a reduction in dyspnoea. These clinical results suggest that
      recanalisation therapy with Neodym-YAG laser and/or balloon dilation with
      additional immunosuppression is suitable in benign stenosis (granulomatous or
      fibrotic), caused by Behet's disease.

PMID- 8739495
TI  - Early expression of intercellular adhesion molecule-1 in the corneal endothelium
      stimulated by endotoxin: an immuno-scanning electron microscopical study.
AB  - Three-dimensional localization of the intercellular adhesion molecule-1 (ICAM-1)
      in the corneal endothelium stimulated by Salmonella typhimurium endotoxin was
      investigated using immuno-scanning electron microscopy (SEM). Samonella
      typhimurium endotoxin, 100 micrograms, was injected in Lewis rats weighing 200
      grams. The animals, including the controls, were sacrificed and both eyes
      enucleated at 0, 3, 12 and 24 hours after injection (n = 3 each time). After
      resection, the corneas were immersed in hypothermic University of Wisconsin
      solution with monoclonal mouse-anti-rat ICAM-1 IgG and then goat-anti-mouse IgG
      coupled to 15 nm gold particles. Then the corneas were prepared conventionally
      for scanning electron microscopy. Histotopographical examination with immuno-SEM
      revealed that ICAM-1 antigen increased on the corneal endothelium by 3 hours
      postinjection. The particles were arranged along the cytoplasmic processes,
      especially at the summits. The number of particles was 3.3 +/- 0.8/microns2 in
      the control, 3.6 +/- 0.8/microns2 at 0 hour, 14.4 +/- 0.9/microns2 at 3 hours,
      25.4 +/- 1.4/microns2 at 12 hours, and 22.7 +/- 2.6/microns2 at 24 hours
      postinjection. ANOVA indicated that the time-course was an important factor (P <
      0.01). Our results showed that ICAM-1 could be augmented in the corneal
      endothelium by endotoxin. The interrelationship between ICAM-1 expression and
      cytoplasmic processes seems to be important for the neutrophil-binding mechanism.

PMID- 8739496
TI  - Hyaluronan, CD44 and fibronectin in rabbit corneal epithelial wound healing.
AB  - Changes in hyaluronan (HA) concentration and stainability were investigated in
      the rabbit cornea after wounds made by exposure to n-heptanol. The HA
      concentration in the cornea increased gradually until day 14 after wounding, and
      then decreased. The HA concentration returned to the normal level 56 days after
      wounding. In the normal control cornea, HA staining was observed in the
      epithelium and stroma. The intensity of HA staining in the epithelium and stroma
      increased until day 3 after wounding, when the epithelium had completely covered
      the defect. At day 28, when the thickness of the corneal epithelium returned to
      the normal level, the intensity of HA staining in the epithelium also decreased.
      However, staining in the stroma was still strong. HA staining in the stroma
      decreased by day 56 after wounding. In parallel experiments, the immunostaining
      for CD44, an HA receptor, and fibronectin (FN) was carried out in the same model.
      The immunostaining in the epithelium of both CD44 and FN was synchronistic with
      the HA staining during the early stages after wounding. These events suggest that
      HA, CD44 and FN cooperatively play important roles in corneal epithelial wound
      healing.

PMID- 8739497
TI  - Effects of BQ-123, an ETA recepter-selective antagonist, on changes of
      intraocular pressure, blood-aqueous barrier and aqueous prostaglandin
      concentrations caused by endothelin-1 in rabbit.
AB  - Endothelin-1 (ET-1) is known to affect the intraocular pressure (IOP) in rabbits.
      We reported that intravitreally administered ET-1 induced biphasic IOP response,
      an early transient IOP rise followed by a subsequent prolonged decrease. In an
      attempt to clarify the role of ET receptor subtypes in the IOP responses
      following ET-1 injection, we studied the effects of ETA receptor-specific
      antagonist, BQ-123, in rabbits. We also evaluated the possible role of
      prostaglandins (PGs) and the disruption of the blood-aqueous barrier (BAB)
      following ET-1 injection in modulating the IOP change. BQ-123 (126.5 or 12.6
      micrograms) was injected into the vitreous (20 microL/eye) of one eye in a group
      of 5 rabbits. Contralateral eyes received the same amount of vehicle in a masked
      randomized fashion. The same amount of ET-1 (0.5 or 0.05 micrograms) was injected
      intravitreally 30 minutes later into both eyes. IOP was measured prior to and
      periodically up to 120 hours after injection using a calibrated pneumatonometer.
      In another experiment BQ-123 (126.5 micrograms) was injected into one eye of 4
      rabbits and the other eye served as a control to observe the effect of BQ-123 on
      the IOP. One hour and 24 hours following the injection of BQ-123 and ET-1,
      approximately 100 microL of aqueous humor was withdrawn by paracentesis. Protein
      concentration was measured by Lowry's method and PGE2 concentration, by
      radioimmunoassay. BQ-123 had no effect on the IOP when used alone. When used in
      combination with ET-1, BQ-123 (126.5 micrograms) significantly inhibited both the
      IOP rise (0.5-1 hour) and the reduction (24-72 hours) caused by ET-1 (0.5
      microgram). BQ-123 (12.6 micrograms) also significantly inhibited the IOP
      reduction (6-8 hours and 72-96 hours) caused by ET-1 (0.05 micrograms). Pre
      injection of BQ-123 (126.5 micrograms) significantly suppressed the increase in
      the aqueous protein and the PGE2 concentration both at 1 and 24 hours. The IOP
      response and the elevation of aqueous protein and PGE2 concentration following ET
      1 injection are at least partly mediated by ETA receptors.

PMID- 8739498
TI  - Morphological study of age-related changes in Fischer rat lens.
AB  - The authors conducted a morphological investigation of age-related changes in the
      lens of male Fischer rats at 6, 12, 18 and 24 months of age. At 6 months, there
      were no abnormalities of particular note other than slight swelling of the
      subcapsular fibers. Moreover, other than a slight decrease in the density of
      epithelial cells and slightly more extensive fiber swelling, there were no
      remarkable changes seen in the lens at 12 months. At 18 months of age, posterior
      invasion by the processes of the cortical lens fibers toward the lens capsule and
      slight swelling of the anterior cortical fibers were seen in addition to the
      above-mentioned changes. By 24 months of age, these changes had become more
      noticeable, with further reduction in the density of epithelial cells, swelling
      and degeneration of both anterior and posterior fibers and extension of the thin
      processes of the equatorial fibers toward the capsule. However, the bow
      configuration at the equator appeared almost normal. These findings indicate that
      the age-related changes in the Fischer rat lens occurred in the epithelial cells
      and superficial layer of the cortical fibers, subsequently leading to the loss of
      clarity in the lens.

PMID- 8739499
TI  - Lens development and crystallin distribution of the early onset hereditary
      cataract in the UPL rat.
AB  - The Upjohn Pharmaceuticals Limited (UPL) rat is a new dominant hereditary
      cataract model with two types of cataract formation, early onset (E-type) and
      late onset (L-type). In the UPL E-type rat cataracts have formed by the time the
      eyes open. The E-type rat also develops microphthalmos and buphthalmos. In this
      study, histological observations of cataract development in the E-type rats were
      performed during the period of fetal development, at birth and at 1, 3 and 62
      weeks of age. In addition, the distribution of alpha- and gamma-crystallins in
      the developing lens was determined using anti-crystallin antisera. Abnormal
      elongation of the lens fibers was first observed on the 13th day of gestation.
      Stratification of lens epithelial cells was present on the 19th day of gestation
      and this change became more severe with age. There was no alteration in alpha-
      and gamma-crystallin expression during the fetal period. The continuity between
      the lens epithelial cells and lens fibers was lost at 3 weeks of age and it was
      assumed that differentiation of lens epithelial cells had ceased. These findings
      suggested that development of the UPL rat E-type cataract was related to an early
      abnormality in lens cell differentiation not involving crystallin expression.

PMID- 8739500
TI  - Light-evoked changes of glycine-like immunoreactivity in the rat retina.
AB  - Glycine is an important inhibitory neurotransmitter in the vertebrate retina.
      Although many reports of glycine localization by the immunocytochemical method
      have been published, none has distinguished the neurotransmitter function of
      glycine from metabolic change. If glycine is the neurotransmitter, it seems that
      it must be affected or released by stimulation. We evaluated the possibility that
      glycine in retinal synapses changes with light stimulation. Glycine-like
      immunoreactivity was found by light microscopy to be present mainly in the inner
      plexiform layer and amacrine cells. In the inner plexiform layer these
      immunoreactive products decreased after illumination. The distribution of glycine
      like immunoreactivity in the rat retina was also investigated after embedding
      anti-rabbit IgG-gold colloidal particles (GCP). In the dark-adapted eyes, glycine
      like immunoreactivity was marked in the inner plexiform layer (27.8 +/- 5.7
      GCP/microns2) and amacrine cells (33.5 +/- 5.5 GCP/microns2). This immunoreactive
      product significantly decreased only in the inner plexiform layer after
      illumination (15.5 +/- 4.5 GCP/microns2). These changes in immunoreactivity may
      reflect the release of endogenous glycine. Our results provide evidence for the
      role of glycine as a retinal neurotransmitter.

PMID- 8739501
TI  - Sodium hyaluronate eyedrops enhance tear film stability.
AB  - Sodium hyaluronate eyedrops can relieve various dry eye symptoms by prolonging
      the stability of the precorneal tear film. To determine the most effective
      concentration of sodium hyaluronate, we studied the concentration-dependent
      effects of sodium hyaluronate eyedrops on the precorneal tear film breakup time
      (BUT) in 12 volunteers. These subjects had a BUT of 10 seconds or less and a low
      tear volume determined with the phenol red thread test. They received four
      different concentrations of sodium hyaluronate eyedrops (0, 0.05, 0.1 and 0.3%).
      BUT was measured noninvasively using a non-contact specular microscope before the
      sodium hyaluronate eyedrop instillation and again after 5, 15, 30, 60, 120 and
      180 minutes. The tear film stability period was prolonged significantly with 0.1%
      and 0.3% eyedrops at all measurement times (P < 0.05), while the eyes treated
      with 0% and 0.05% eyedrops showed no significant prolongation of tear film
      stability at any measurement times. The findings of this study confirm that
      sodium hyaluronate at a concentration of at least 0.1% is required to delay the
      breakup of the precorneal tear film.

PMID- 8739502
TI  - Assessment of mitochondrial gene in proliferative vitreoretinal tissues from
      patients with familial diabetes mellitus.
AB  - Fibrovascular tissues obtained at therapeutic vitrectomy from 22 patients with
      proliferative diabetic retinopathy were studied for a mutation of tRNALEU(UUR) at
      nucleotide position (np) 3243 of mitochondrial DNA (mtDNA). We found a mutation
      of mtDNA in the vitreous sample of one patient, a 44-year-old woman who had
      maternally inherited, familial, non-insulin-dependent diabetes mellitus of 25
      year duration with recurrent vitreous hemorrhages due to proliferative
      retinopathy. Heteroduplex analysis also detected the mutant-type mtDNA in the
      vitreous sample of this patient. The abnormality was, however, not observed in
      the peripheral blood sample from either this patient orr her family members with
      diabetes mellitus. The other 21 patients were negative for the mutation in
      vitreous specimens as well as in peripheral blood. Although a firm conclusion
      cannot be drawn from a single case report, our observations suggest that this
      case was an example of tissue-specific expression of mtDNA mutation. Further
      studies of a larger number of patients with familial diabetes mellitus seem
      justified.

PMID- 8739504
TI  - Detection of congenital color vision defects using heteroduplex-SSCP analysis.
AB  - Gene deletion and hybrid gene formation result in congenital red and green color
      vision defects. The innumerable variations in these defects require the
      development of appropriate methods for detailed investigation. We used
      heteroduplex-single-strand conformation polymorphism (SSCP) analysis to detect
      the gene variations in subjects with congenital red and green color vision
      defects. For comparison, we also used polymerase chain reaction restriction
      fragment length polymorphism (PCR-RFLP) to detect these defects. In all 13 protan
      and 9 of the 15 deutan subjects, defects of the red or green pigment gene could
      be identified by either heteroduplex-SSCP or PCR-RFLP analysis. Through
      heteroduplex-SSCP analysis, sequence polymorphism was detected in exon 5 of the
      green pigment gene. One polymorphic sequence was present in 8 of 21 trichromats
      but in only one of 17 dichromats, showing a biased distribution. A specific
      variation was found in one protan by SSCP analysis. Heteroduplex-SSCP procedures
      are useful for objective clinical diagnostic testing and for further study of
      color vision variations because of their simplicity and reliability and because
      they provide more information.

PMID- 8739503
TI  - HTLV-I associated retinochoroidal degeneration.
AB  - A review of 100 patients with HTLV-I associated myelopathy revealed 9 cases of
      retinochoroidal degeneration. The ocular disease was characterized by late onset,
      usually bilateral, progressive degenerative changes of the retina and choroid,
      which were preceded by, concurrent with, or followed by HTLV-I associated
      myelopathy. Ophthalmoscopic features were consistent with diffuse or localized
      retinochoroidal degeneration, the resultant functional disturbance being
      dependent on the extent of disease. It is noteworthy that the clinical picture in
      3 cases was indistinguishable from primary retinitis pigmentosa. However, based
      on the prevalence of primary retinitis pigmentosa in the general population
      estimated from a questionnaire to ophthalmologists in the area, it was plausible
      that retinitis pigmentosa in HTLV-I associated myelopathy does not represent a
      coincidence of primary retinitis pigmentosa but a meaningful association with the
      neurological disease. Hence, we propose the existence of HTLV-I associated
      retinochoroidal degeneration (HARD) as a distinct disease. An additional study
      revealed that 21 (17.8%) of 118 patients with isolated, retinitis pigmentosa were
      seropositive for HTLV-I, the ratio being not significantly different from that in
      the general population. Therefore, the hypothesis that HTLV-I also contributes to
      an isolated form of retinochoroidal degenerative disease is not readily
      acceptable.

PMID- 8739505
TI  - HLA serological and class II genotyping in sarcoidosis patients in Japan.
AB  - To investigate the HLA alleles that contribute to the genetic susceptibility to
      sarcoidosis, HLA serological typing was performed in 75 patients with sarcoidosis
      and 150 controls using the standard complement-dependent microcytotoxicity
      method. The genomic DNAs of the 75 patients and 130 of the 150 controls were used
      to analyze HLA-DRB1, -DQA1, -DQB1 and -DPB1 alleles, utilizing the polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
      Serological typing showed that the frequencies of HLA-DR52, -DR5, -DR6 and -DR8
      were significantly increased in the patients compared to the controls. In PCR
      RFLP genotyping, the frequencies of the DR52-associated DRB1 alleles (DRB1*11,
      DRB1*14), DRB1*08, DQA1*0501 and DQB1*0301 were significantly increased in the
      patients compared to the controls. The frequencies of the DRB1*12 alleles were
      also increased among the patients, but this increase was not significant. The
      frequencies of DRB1*0101, DQB1*0501, and DPB*0402 were significantly lower in the
      patients than in the controls. The significant increases in the frequencies of
      DQA1*0501 and DQB1*0301 could be due to the linkage disequilibrium between the
      DR52-associated DRB1 alleles and DQA1*0501 and DQB1*0301 alleles among the
      Japanese. The significantly increased frequency of the DR8 (DRB1*08) haplotype,
      which lacks the DRB3 gene encoding DR52 antigen, suggested that the DR5
      (DRB1*11), DR6 (DRB1*14) and DR8 (DRB1*08) of the DRB1 alleles may determine the
      susceptibility to sarcoidosis among the Japanese.

PMID- 8739507
TI  - Ophthalmic artery flow velocity after physical exercise in healthy men.
AB  - This study was conducted to evaluate the effects of physical exercise on blood
      flow velocity in the ophthalmic artery of healthy men. Color Doppler imaging,
      which permits rapid noninvasive imaging of the ophthalmic artery, was performed
      in 11 healthy male adult volunteers to compare pre- and post-exercise
      measurements of blood flow velocity. After submaximal physical exercise, systolic
      blood flow velocity (Vmax) and time-averaged blood flow velocity (Vmean)
      increased significantly, but returned to pre-exercise levels 5-10 minutes after
      the completion of physical exercise. There were no significant changes in minimum
      end-diastolic blood flow velocity (Vmin), resistance index (RI) or pulsatility
      index (PI). The RI and PI parameters are considered to reflect vascular
      resistance. Our results indicate that submaximal physical exercise increased the
      blood flow velocity, but did not alter the resistance index of the ophthalmic
      artery.

PMID- 8739506
TI  - Retinoblastoma in Turkey--treatment and prognosis.
AB  - The treatment modalities and prognosis of 636 retinoblastoma (RB) cases diagnosed
      and treated in our specialist center between 1963 and 1994 were evaluated.
      Patient age ranged from 20 days to 16 years, the mean age being 2.2 years (26.4
      months). Of the 636 cases, 441 were unilateral and 195 were bilateral.
      Enucleation was the most frequent treatment employed in unilateral RB patients
      (412 cases). Follow-up treatment included exenteration (48 cases), radiotherapy
      (154 cases) and chemotherapy (108 cases) for cases with optic nerve invasion
      and/or orbital recurrence following enucleation. Seventeen cases displayed
      massive proptosis, ocular damage and blindness at initial presentation and
      underwent exenteration as the initial treatment. Two cases were subjected to
      external beam radiotherapy without invasive surgical procedures. Ten cases
      regressed spontaneously without treatment. For bilateral cases, the most frequent
      treatment used was enucleation for one eye and radiotherapy for the other (132
      cases). Adjuvant treatment included exenteration (9 cases) and chemotherapy (50
      cases) depending on orbital recurrence and/or systemic metastasis. Spontaneous
      bilateral regression was noted in one case. Six cases underwent bilateral
      external beam radiotherapy without surgery. One eye of the remaining 56 bilateral
      cases underwent enucleation. The treatment for the contralateral eyes included
      cryotherapy in 14 cases, enucleation in 11 cases, Cobalt plaque (Co plaque)
      therapy in 10 cases, photocoagulation in 6 cases and exenteration in one case. No
      treatment was undertaken in the contralateral eyes of 14 cases. Secondary
      treatment modalities employed in these 56 bilateral cases were radiotherapy (11
      cases), chemotherapy (8 cases), Co plaque (8 cases) and exenteration (5 cases).
      Treatment complications were detected in 25 cases followed for at least 18
      months. Eighteen cases had radiation cataracts and 6 of these 18 patients
      underwent intraocular lens implantation. Post-radiation orbital malignancy
      (osteosarcoma) was noted in two cases aged 14 and 15 years. Phthisis bulbi was
      observed in three cases and radiation keratitis in two cases. The overall
      survival rate was 82.2% after a mean follow-up of 5 years. The survival rate of
      unilateral cases was 82.8% and that of bilateral cases was 81.1% at 5 years.

PMID- 8739508
TI  - Bilateral choroidal osteomas associated with histiocytosis X.
AB  - A 15-year-old Japanese girl complained of decreased visual acuity in the left eye
      of 1-month duration. Histiocytosis X had been diagnosed when she was 2 years old
      based on examination of biopsies of skin and cervical lymph nodes and bone marrow
      aspirations. She had been in complete remission for 7 years. She exhibited the
      characteristic ophthalmoscopic, ultrasonographic, and radiologic features of
      bilateral choroidal osteomas.

PMID- 8739509
TI  - Differential diagnosis of macular breaks by microperimetry using the scanning
      laser ophthalmoscope.
AB  - To improve the differential diagnosis of macular breaks by microperimetry using
      the scanning laser ophthalmoscope (SLO), we studied 50 consecutive breaks
      detected by biomicroscopy and indirect ophthalmoscopy. The full-thickness macular
      break was easily diagnosed using only biomicroscopy and indirect ophthalmoscopy
      because the macular break had a cuff in 22 of the eyes. SLO microperimetry also
      showed an absolute scotoma within the macular break and a relative scotoma on the
      cuff in these 22 eyes. However, in the other 28 eyes it was impossible to
      distinguish between the full-thickness macular breaks and pseudo-macular breaks
      or lamellar macular breaks using only biomicroscopy and indirect ophthalmoscopy
      because of the absence of a cuff. However, SLO microperimetry differentiated full
      thickness macular breaks from pseudomacular breaks or lamellar macular breaks in
      these 28 eyes. SLO microperimetry is indispensable for determining the prognosis
      of and the surgical indication requirements for idiopathic macular breaks.

PMID- 8739510
TI  - Pharmacokinetics of topically applied ciprofloxacin in rabbit tears.
AB  - Fluoroquinolones provide an important single antibiotic therapy for bacterial
      keratitis caused by Staphylococcus aureus and numerous gram-negative bacteria,
      including Pseudomonas aeruginosa. The pharmacokinetics of three ocular
      fluoroquinolones, norfloxacin (CHIBOXIN, Merck, Sharp & Dohme), ciprofloxacin
      (CILOXAN, Alcon Laboratories), and ofloxacin (OCUFLOX, Allergan Pharmaceuticals),
      have been studied in the human eye and in both the normal rabbit eye and rabbit
      models of keratitis. However, the pharmacokinetics of ciprofloxacin have not been
      previously studied in the tear film of rabbits. This study was done to determine
      the pharmacokinetics of topical ciprofloxacin in the rabbit tear film. Two drops
      of CILOXAN were applied to the eyes of normal rabbits. Tear samples were
      collected at 5, 10 and 30 minutes, and 1, 2, 4 and 6 hours after topical drug
      application. Tear samples were analyzed for ciprofloxacin concentrations by HPLC.
      Ciprofloxacin concentrations reached a peak at 5 minutes, then declined in a
      manner similar to that reported for norfloxacin and ofloxacin. The ciprofloxacin
      concentrations in tears were substantially higher throughout the length of the
      study than the MIC90 for most ocular pathogens including Staphylococcus aureus
      and Pseudomonas aeruginosa.

PMID- 8739511
TI  - Post-abortion complications after interruption of pregnancy with misoprostol.
AB  - The high incidence of abortion in Brazil and the increased use of misoprostol
      among women having clandestine/unsafe abortions has led to an interest in
      evaluating whether there is an association between the use of misoprostol and the
      incidence of septic complications post-abortion. To test this association, a
      retrospective cohort study was conducted with 1840 women treated post-abortion at
      the Instituto Materno-Infantil de Pernambuco (IMIP) between 1988 and 1992.
      Incidence of infection (4.2%) was lower in women stating they had used
      misoprostol than in those stating that the abortion was not induced (7.9%) and
      twelve times lower than in women stating that they had used other methods
      (49.4%). These results suggest that misoprostol is a safe, inexpensive method for
      inducing abortion, and leads to fewer complications and consequently shorter
      hospital stays. Misoprostol should be considered a viable option in situations
      where induction of abortion is legal or medically indicated.

PMID- 8739512
TI  - Plasma human chorionic gonadotropin levels after induced abortion.
AB  - In the present study, we evaluated the elimination time and the disappearance
      curve of maternal plasma hCG after induced abortion in 44 patients. The patients
      were divided into two groups: patients in group 1 had gestations at or at less
      than 8 weeks and group 2 consisted of patients with gestations at more than 8
      weeks in whom sharp curettage was utilized. The entire group had a mean of 48,342
      mIU/ml baseline level of maternal plasma hCG. After the evacuation of the uterine
      cavity, a rapid decrease of plasma hCG occurred within the first week, followed
      by a gradual decline until elimination was total. The mean disappearance time of
      plasma hCG was 30 days. The disappearance curve of hCG was found to be in a form
      similar to that described before. No significant difference was found between the
      two groups. We conclude that when the appropriate method is used for pregnancy
      termination, the time between the procedure and disappearance of hCG depends on
      the initial hCG value.

PMID- 8739514
TI  - Luteinizing hormone releasing hormone agonist for postpartum contraception.
AB  - OBJECTIVE: To compare the effects of a GnRH agonist upon ovarian function,
      bleeding pattern, and nursing practice in two groups of Mexican women during the
      postpartum period. DESIGN AND PATIENTS: Two doses of a GnRH agonist (300-600
      micrograms) were investigated during the postpartum period in fully breastfeeding
      mothers at 6 weeks postpartum. A total of 29 women who desired to breast feed for
      at least 6 months were allocated in three study groups; group I (control); group
      II, taking 300 micrograms; and group III, taking 600 micrograms. RESULTS: After
      treatment initiation, an increase of estrone levels was observed among treated
      women; thereafter, irregular fluctuations of estrone levels were observed, mainly
      among women from group III. All the control women and two participants from group
      III ovulated during the study. Moderate bleeding was registered in most of the
      women from group I, while amenorrhea and spotting were observed in participants
      from groups II and III, respectively. There was no significant effect of the
      treatment on nursing practice between groups. CONCLUSION: GnRH agonists have
      advantages over steroids for hormonal contraception during the postpartum period
      in breastfeeding women. Symptoms of hypoestrogenism were not reported any time in
      either the controls or the treated groups, as estrone levels were not suppressed
      to menopausal values. Once-daily administration of GnRH agonist could be a
      reliable, acceptable and safe contraceptive method during the postpartum period
      in breastfeeding women. More information is required to establish GnRH analog
      contraceptive efficacy.

PMID- 8739513
TI  - GnRH agonist for postpartum contraception: biochemical, hormonal and endometrial
      effects.
AB  - OBJECTIVE: To determine whether GnRH agonist administration induces changes in
      biochemical, hormonal and endometrial parameters in breastfeeding women. DESIGN
      AND PATIENTS: Starting at 6 weeks postpartum, fully breastfeeding mothers began
      treatment with GnRH agonist, receiving 300 micrograms and 600 micrograms per day
      by nasal spray for 6 months. A third group of breastfeeding women who were users
      of IUDs served as controls. Eighteen biochemical analyses were quantified in
      serum. Blood samples were collected at 0, 3 and 6 months after treatment and
      endometrial biopsies were obtained at 0 and 6 months. No other method of
      contraception was employed. RESULTS: Interindividual and intergroup differences
      were observed in clinical chemistry. According to the hormonal levels and the
      histopathologic analysis, various grades of follicular activity were found in the
      treated groups. No pregnancies occurred. CONCLUSION: Because GnRH agonist
      treatment had no significant deleterious effects on the parameters studied, this
      treatment could represent a feasible and safe approach to postpartum
      contraception.

PMID- 8739515
TI  - Beliefs about Depo-Provera among three groups of contraceptors.
AB  - This article examines the beliefs about Depo-Provera held by three groups of
      contraceptors utilizing urban family planning clinics in the United States (n =
      836). Patients choosing Depo-Provera, oral contraceptives, and Norplant were
      asked about their beliefs regarding Depo-Provera in the following four domains:
      effectiveness in preventing pregnancy, convenience, side-effects, and risk to
      health; and also for their perceptions regarding the physical discomfort and cost
      associated with the method. Findings reveal that patients choosing the pill and
      Norplant give Depo-Provera significantly lower ratings for both convenience and
      effectiveness than do Depo-Provera acceptors. Given the documented effectiveness
      of Depo-Provera, this is a potential cause for concern. Moreover, Norplant and
      pill choosers are most likely to hold inaccurate beliefs regarding both the cost
      of Depo-Provera, and certain side-effects associated with its use. Although more
      than half of all patients believe the Depo-Provera would cause menstrual changes
      and weight gain, it is noteworthy that the proportions are not higher, given
      their known association with the method. Knowledge about the likelihood of these
      side-effects is essential, particularly for those choosing Depo-Provera.
      Implications for physicians, counselors, and other family planning professionals
      are discussed.

PMID- 8739516
TI  - Sexual activity during and after pregnancy.
AB  - The factors related to sexual behavior during pregnancy and after childbirth were
      studied in 352 Nigerian women. Sexual frequency was higher during the postnatal
      period (1.7 times per week) compared to the pregnancy period (1.5 times per
      week). Coital frequency also showed no difference for the various social class
      and age groups but was more prevalent among the primigravidas compared to the
      higher parity groups (p < 0.05). Vulval itching was experienced in 246 (69.9%)
      women although this had no effect on sexual activity in 114 (46.5%) of them. The
      earliest date of resumption of sexual intercourse following childbirth was 3 days
      while the latest was 84 weeks. However, sexual activity was resumed between 6 and
      12 weeks after delivery in 114 respondents (48.7%). The overall mean resumption
      time for sexual activity postpartum was 16.5 weeks. The longest mean resumption
      time occurred for breastfeeding/cultural reasons (41 weeks) and family planning
      reasons (23.9 weeks) while the shortest resumption time occurred for pleasure
      reasons (3.2 weeks). The attitude toward sexuality among African women during
      pregnancy and after childbirth can be said to be positive and purposeful, and
      this should be taken into account in the overall management of sexuality in the
      pregnant African woman.

PMID- 8739517
TI  - Causative factors in first trimester abortion failure.
AB  - OBJECTIVE: To evaluate the main contributors to failed first trimester abortions.
      PATIENTS AND DESIGN: Forty-two cases of unintentional continued pregnancy were
      detected among 23,000 termination procedures performed between 1989 and 1995. The
      patients were diagnosed either at follow-up visits or at the time of operation
      due to abnormal pelvic findings or discrepancy between the expected and obtained
      tissue. RESULTS: The failure rate was found to be 0.18%. Among the patients with
      failed abortion 8 patients had unsuspected anomalies; two of these patients
      conceived with an intrauterine device in position; 7 patients had uterine
      malposition (2 markedly anteverted and 5 markedly retroverted), and 2 patients
      had leiomyomas. No genital disorder was identified in the remaining 25 women.
      Among these 25 women, 10 had gestations beyond 8 weeks, for which suction
      curettage followed by sharp curettage was performed. Among the remaining 15 in
      whom only suction curettage was used for termination, 13 had less than 6 weeks of
      gestation at the time of pregnancy termination. CONCLUSION: When a termination
      fails, when scanty tissue is obtained, or when doubt exists about the
      termination, an extrauterine pregnancy must be ruled out and other causes of
      termination failure should be considered such as technical failure, uterine
      anomaly, or malposition.

PMID- 8739518
TI  - Biochemical characterization of lipopolysaccharides extracted from a hydrophobic
      strain of Pasteurella multocida.
AB  - Lipopolysaccharides were extracted from freeze-dried cells of Pasteurella
      multocida strain P-1581 (serotype 8) by the phenol-chloroform-petroleum ether
      method and biochemically analysed using standard procedures. The primary neutral
      sugars were glucose, galactose and heptose. No deoxy sugars were detected. Amino
      sugars included galactosamine, glucosamine and glucosamine-6-phosphate. 3-Deoxy-D
      manno-2-octulosonic acid was present at a relatively low concentration. The
      analyses included identification and quantification of phosphate and alanine. The
      primary fatty acids and their approximate relative ratios were 3
      hydroxytetradecanoate and tetradecanoate 2:1. Tetradecanoic acid was bound almost
      exclusively by ester linkages. 3-Hydroxytetradecanoic acid was bound primarily by
      amide linkages, although significant numbers of ester-bound residues were noted.
      Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analyses indicated
      that the lipopolysaccharides were of low molecular weight.

PMID- 8739519
TI  - The antimicrobial susceptibility of Staphylococcus species isolated from canine
      dermatitis.
AB  - In a retrospective study, 1538 strains of beta-haemolysin-producing
      Staphylococcus species isolated from dermatitis in dogs at three veterinary
      clinical microbiology laboratories in Norway during 1986-87 and 1993-94 were
      investigated for their antimicrobial susceptibility. None of the strains was
      resistant to cloxacillin, cephalexin or the quinolones enrofloxacin and
      ciprofloxacin. More than 96% of the strains were susceptible to trimethoprim
      sulphonamide, bacitracin and fucidic acid. Between 67% and 89% of the strains
      were susceptible to erythromycin, lincosamides, tetracycline, neomycin and
      chloramphenicol. Only 37.9% of the strains were susceptible to penicillin. The
      frequency of penicillin resistance increased significantly between the first and
      second periods, from 46.0% to 58.6%. The frequency of resistance to lincomycin,
      clindamycin and erythromycin also increased significantly between the first and
      second periods, from 3.0%, 2.1% and 3.3% to 25.5%, 19.5% and 24.8%, respectively.
      A moderate increase in resistance to tetracycline was also noted, from 20.4% in
      the first to 27.6% in the second period. On the other hand, the frequency of
      resistance to trimethoprim-sulphonamide decreased significantly from 4.1% in the
      first to 0.9% in the second period. Many different resistance patterns were
      observed in each period. However, the proportion of multiresistant strains
      increased from 2.1% in the first to 10.2% in the second period. There was a
      decrease in resistance to the combination of trimethoprim-sulphonamide and
      penicillin from the first to the second period. Resistance to the combination of
      lincosamides and penicillin increased. For the combinations penicillin
      tetracycline-lincosamides, penicillin-lincosamides-erythromycin, and penicillin
      tetracycline-lincosamides-erythromycin, there was a striking increase in
      resistance between the first and the second periods.

PMID- 8739521
TI  - Characterization of the complex carbohydrates in the zona pellucida of mammalian
      oocytes using lectin histochemistry.
AB  - The objective of this study was to characterize the glycoconjugates present in
      the zona pellucida of the follicular oocytes in sheep, goats and pigs. The zona
      pellucida was stained with periodic acid-Schiff, low iron diamine, high iron
      diamine, and nine different lectin horseradish conjugates: Con-A, SBA, DBA, PNA,
      RCA-I, GSA-II, WGA, LTA and UEA-I. Staining with DBA, PNA, SBA and RCA-I was
      performed with and without saponification with KOH and sialidase digestion. The
      results showed the presence of neutral and acidic glycoconjugates with different
      terminal sugars and also sialic acid radicals in the zona pellucida of all the
      animal studied. In particular, the positive staining with WGA, SBA, PNA and RCA-I
      suggests the presence of oligosaccharides with N-acetyl-D-glucosamine and sialic
      acid linked to the penultimate beta-N-acetyl-D-galactosamine and to the
      disaccharide galactosyl-(beta 1-3)-N-acetyl-D-galactosamine. The terminal
      trisaccharide sialic acid galactosyl-(beta 1-4)-N-acetyl-D-glucosamine was
      identified only in the zona pellucida of ovine and porcine oocytes. Thus, the
      zona pellucida exhibited species-specific variations in the content and
      distribution of lectin-binding patterns that may reflect the species specificity
      of gamete interaction.

PMID- 8739520
TI  - High sensitivity to streptozotocin in herbivorous voles, Microtus arvalis,
      compared to mice.
AB  - Herbivorous voles, Microtus arvalis, have characteristics similar to herbivores
      in that their hepatic glycolytic enzyme activities are relatively low. The
      effects of a single low dose (100 mg/kg body weight) of streptozotocin (STZ) in
      voles were studied and the difference in sensitivity to or toxicity of STZ in
      voles and C57BL/6 mice was compared. In voles which received STZ, the cumulative
      incidence of glycosuria reached 53% by 4 weeks after administration. The diabetic
      voles showed marked increases in their blood glucose and plasma free fatty acid
      concentrations and a significant decrease in plasma immunoreactive insulin
      concentrations. Their hepatic hexokinase, glucokinase, glutathione peroxidase and
      glutamate dehydrogenase activities decreased significantly and lesions were
      widely observed in the liver, kidney and pancreas. The activities of glutathione
      peroxidase, a scavenger of H2O2, decreased significantly in their liver and
      pancreas. These changes were not observed in C57BL/6 mice which received STZ. The
      higher sensitivity to and toxicity of STZ in voles than in mice are considered to
      be caused by the characteristically low activities of glycolytic enzymes and
      glutathione peroxidase in the tissues of voles. Voles may be a good model for
      studying the mechanisms of cytotoxicity by STZ in herbivorous animals.

PMID- 8739522
TI  - An increased incidence of mastitis caused by Prototheca species and Nocardia
      species on a farm in Sao Paulo, Brazil.
AB  - Mastitis caused by Prototheca spp or Nocardia spp is considered to be difficult
      to treat. Both microorganisms are contaminants commonly found in soil. The
      occurrence of mastitis caused by these agents was studied in a particular dairy
      farm. In this herd, the animals were kept at pasture overnight and during daytime
      were brought to a pen where they were fed. This pen accumulated mud and faeces,
      particularly in the rainy season. During milking, pre-dipping of the teats was
      performed with an iodide solution, but they were not washed, so a layer of soil
      and faeces remained which may have contaminated the milking equipment. The herd
      comprised 91 lactating animals and 47 dry cows. For microbiological examination,
      107 milk samples were collected from lactating cows and 186 samples of mammary
      secretions from the dry cows. Prototheca spp were isolated from 14.55% of the
      milk samples and Nocardia spp from 4.55%. Prototheca spp were isolated from 8.06%
      of the secretion samples from dry cows and Nocardia spp were isolated from 2.15%
      samples. The high occurrence of mastitis due to these environmental agents
      reflects the problem of keeping animals in muddy pastures and pens, and the
      defective pre-milking hygiene for the teats.

PMID- 8739523
TI  - The distribution pattern of Sarcocystis species, their transmission and
      pathogenesis in sheep in Fars Province of Iran.
AB  - Of 1362 sheep examined during two years in Fars Province of Iran, 786 (57.7%)
      were positive for Sarcocystis spp. The prevalence was significantly higher (p <
      0.05) in animals owned by nomadie Assyrians (67.95%) than in those owned by local
      people (41.86%). More of the animals above 2 years age were infected (69.98%)
      than young ones (30.02%). Females had a higher prevalence of infection (61.07%)
      than males (38.93%) but most of the males were younger. There was no variation in
      the infection rate during spring, summer or autumn, but it was low in winter. The
      species observed were Sarcocystis gigantea, predominantly in oesophagus, S.
      medusiformis, mainly in diaphragm, S. tenella in the oesophagus, diaphragm,
      tongue and heart, and S. arieticanis in the oesophagus, tongue and occasionally
      in the diaphragm. In transmission studies, the prepatent period for S. gigantea
      and S. medusiformis and for the two microscopic species was 11-13, 10 and 8-12
      days, respectively. The infection could not be transmitted to hamsters and guinea
      pigs. The macroscopic species were almost non-pathogenic but were responsible for
      economic losses because of rejection of carcases or parts thereof at slaughter.
      The microscopic species caused tissue damage to the affected organs, resulting in
      haemorrhages, mononuclear infiltration and necrotic changes.

PMID- 8739524
TI  - The haematological and biochemical effects of the gastrointestinal nematodes
      prevalent in camels (Camelus dromedarius) in central Saudi Arabia.
AB  - Coprological examinations on 1200 Najdi camels (Camelus dromedartus) in the
      Gassim region of central Saudi Arabia between October 1992 and September 1993
      revealed the presence of strongyle-type, Nematodirus and Strongyloides eggs. In
      addition, examination of the gastrointestinal tracts of 240 camels slaughtered in
      different abattoirs in the Gassim region from March to August 1994 revealed 11
      species of helminths. Infection with gastrointestinal trichostronglyes resulted
      in normocytic, normochromic anaemia. Adult infected camels showed leukocytosis, a
      decrease in total serum protein concentration and increases in blood urea
      concentration and in serum creatine phosphokinase activity.

PMID- 8739525
TI  - The disposition kinetics and residues of fenvalerate in tissues following a
      single dermal application to black Bengal goats.
AB  - The disposition kinetics of fenvalerate were studied in goats after dermal
      application of 100 ml of 0.25% (w/v) solution. The insecticide persisted in the
      blood for 72 h. The mean (+/- SEM) Vd(area) and apparent t 1/2 (beta) were 9.92
      +/- 1.44 L/kg and 17.51 +/- 2.65 h, while the AUC and ClB values were
      respectively 82.15 +/- 7.40 micrograms h/ml and 0.56 +/- 0.05 L/(kg h). Four days
      after the dermal application, the highest concentration of fenvalerate residues
      was found in the adrenal gland, followed by the biceps muscle, omental fat,
      liver, kidney, lung and cerebrum in that order. Fenvalerate caused hyperglycaemia
      but had no effect on serum protein and cholesterol levels. Serum
      acetylcholinesterase activities were increased after 24 h but were below the
      initial values from 48 to 120 h.

PMID- 8739526
TI  - Climatic factors associated with the infection of herds of cattle with bluetongue
      viruses.
AB  - The incidence of bluetongue virus infection of 15 cattle herds in Queensland,
      Australia, was determined by a serum neutralization test. The maximum temperature
      (degree C), minimum temperature (degree C) and rainfall (mm) data were obtained
      from the meteorological recording stations closest to each herd. Using unweighted
      least-squares regression analysis, the best statistical model explaining the most
      variability in the herd incidence rate included the ratio between the maximum and
      minimum temperature recorded at both 1 month and 6 months preceding
      seroconversion, and rainfall recorded at both 2 months and 6 months preceding
      seroconversion. More than 90% of the variability in the incidence of bluetongue
      virus infection in the herds was explained by the model, a considerable
      improvement on previous models that used prevalence data. The prospective nature
      of the study also supports a strong causal relationship between climatic factors
      and the occurrence of infection in cattle herds.

PMID- 8739527
TI  - The lesional changes and pathogenesis in the kidney in African swine fever.
AB  - African swine fever is a viral haemorrhagic disease of pigs which has been used
      as a model for the study of viral haemorrhagic diseases in man. The acute course
      of the disease is characterized by acute proliferative glomerulonephritis, with
      viral replication in mesangial cells and occasional focal necrosis of the renal
      tubular system; hyperplasia of the collecting ducts is associated with evident
      virus replication. Haemorrhages have been attributed to endothelial dysfunction,
      aggravated by virus replication in endothelial cells in the final stages of the
      disease. The renal interstitium displays intense oedema and an infiltrate largely
      composed of macrophages. Virus replication has also been observed in fibroblasts
      and in the smooth-muscle cells of arterioles and venules. In subacute-chronic
      forms of the disease, various types of glomerulonephritis are observed, ranging
      from mesangial proliferative glomerulonephritis to focal and segmental hyalinosis
      associated with immune-mediated phenomena. No striking changes are reported in
      the renal tubular system. Interstitial haemorrhages are associated with
      diapedesis due to immunologically mediated events. The interstitium has also been
      found to contain a lymphohistiocytic infiltrate with abundant plasma cells. No
      evidence has been reported of viral replication in any cell population.

PMID- 8739528
TI  - Lipoprotein(a) in 505 hospitalized patients with various pathological states:
      correlations with cardiovascular diseases and therapies.
AB  - OBJECTIVE: Our aim was to study the lipoprotein (a) (Lp(a)) levels in various
      pathological states. EXPERIMENTAL DESIGN: This investigation was prospective and
      included a healthy control group. SETTING: This study was carried out in two
      internal medicine and angiology services in teaching hospitals. PATIENTS: 505
      patients were included with various diseases: 66 acute infections, 9 HIV
      infections, 25 cancers, 86 diabetes, 36 systemic diseases, 94 atheromatous
      vascular disease, 27 arterial hypertensions. A control group was composed of 21
      healthy subjects. INTERVENTIONS: There was no therapeutic intervention but
      cardiovascular treatments were recorded. MEASURES: Serum Lp(a), total
      cholesterol, triglycerides, HDL-cholesterol, calculated LDL-cholesterol,
      apolipoproteins A-I and B were measured together with inflammatory parameters,
      serum creatinine, proteinuria, serum aminotransferase activity. RESULTS: There
      was no difference in Lp(a) levels between controls and each patient group.
      However, a correlation was found in systemic diseases between Lp(a) and C
      reactive protein (r = 0.371, p = 0.026) or serum albumin concentration (r =
      0.453, p = 0.006). In hypertension, Lp(a) correlated with serum creatinine (r =
      0.420, p = 0.03). In the whole patient population, Lp(a) was correlated with
      cholesterol (r = 0.156, p = 0.0001), apolipoprotein B (r = 0.215, p = 0.0001),
      age (r = 0.108, p = 0.015), arterial events (r = 0.174, p = 0.0001) and platelet
      anti-aggregant drugs (r = 0.169, p = 0.0001). CONCLUSIONS: Lp(a), was related to
      atheromatous events and in systemic diseases to inflammation, suggesting that
      Lp(a) might vary in some patients in a manner similar to acute phase proteins.

PMID- 8739529
TI  - Thrombo-embolectomy and thrombolytic therapy in acute lower limb ischaemia. A
      five year experience.
AB  - Between 1988 and 1993, 82 patients with a median age (iq range) of 81 (73-87)
      years underwent thrombo-embolectomy (TE) and thrombolysis for acute lower limb
      ischaemia at the Royal Hallamshire Hospital, Sheffield. 28 patients (Group 1)
      underwent TE prior to the introduction of thrombolysis in 1991. TE with
      intraoperative thrombolysis (IT) as an adjunct was performed in 34 patients
      (Group 2) and 20 patients (Group 3) were treated using percutaneous thrombolysis
      (PT) in the first instance. 41 of these patients were in AF at presentation.
      Although 24 were on digoxin, only 4 were on warfarin. Group 3 patients were
      younger (p < 0.05; ANOVA) with a longer duration of ischaemia (p < 0.05; ANOVA)
      and had less limbs suffering a sensorimotor deficit (p = 0.007; chi 2) compared
      with Groups 1 and 2 which were similar in these respects. Overall mortality was
      17%. Successful revascularisation was achieved in 18 (64%), 28 (82%) and 15 (75%)
      patients in Groups 1, 2 and 3 respectively. 14 of the 15 patients successfully
      treated initially by PT required further intervention in order to maintain
      revascularisation. Revascularisation failure was associated with the presence of
      a sensorimotor deficit but not associated with patient age or duration of
      ischaemia.

PMID- 8739530
TI  - Our first experience applying simultaneous bilateral carotid endarterectomy.
AB  - Simultaneous bilateral carotid endarterectomy (SBCE) has been very rarely cited
      in the international literature. Twelve patients underwent 24 SBCE's (Group A).
      They were compared with 22 bilateral staged endarterectomies in 11 (Group B) and
      155 cases with unilateral endarterectomies (Group C). The indications and
      surgical management were similar and the accompanying risk factors were
      comparable in the 3 groups. Shunt or patch was not used and occlusion time was 13
      +/- 2'. Total occlusion time in the SBCE was 25 +/- 3'. The results are
      comparable in the 3 groups. In the SBCE group one case of TIA was particularly
      noted together with another case with transient vocal cord paresis; however no
      death, myocardial infarct, respiratory problems or permanent damage of the
      central nerves were observed in this group. Despite the small number of our
      patients together with that of the international literature, it seems that a
      better preoperative assessment of the function of the circle of Willis in
      association with meticulous surgical technique and proper patient selection,
      encourages the tactics of simultaneous bilateral carotid endarterectomy.

PMID- 8739531
TI  - The site of residual abnormalities in the leg veins in long-term follow-up after
      deep vein thrombosis and their relationship to the development of the post
      thrombotic syndrome.
AB  - Two major sequelae of deep vein thrombosis (DVT), obstruction to outflow due to
      the presence of residual thrombus and reflux due to valvular damage, may
      contribute to the development of the post-thrombotic syndrome (PTS). We studied
      the nature and site of residual abnormality, non-invasively with duplex
      ultrasound, in the veins of 69 limbs in 66 patients, 1 to 6 years after primary
      acute DVT. There were clinical features of the PTS in 27 limbs and 42 legs were
      asymptomatic. The pattern of duplex abnormalities was complex and varied for both
      the PTS and asymptomatic groups. The proportion of abnormal common and external
      iliac veins and abnormal common, deep and superficial femoral veins was similar
      for limbs with the PTS and asymptomatic limbs. Twenty-six per cent of legs with
      the PTS had reflux at the saphenofemoral junction compared with 19% asymptomatic
      legs (difference not significant). The PTS was associated with proportionally
      more abnormal popliteal veins (81% vs 55%) and posterior tibial veins (PTV),
      PTV#1 (41% vs 21%) and PTV#2 (41% vs 14%) when compared with asymptomatic limbs.
      The odds ratio for a popliteal vein abnormality being associated with the PTS was
      3.63 (95% CI 1.16 to 11.43). The odds ratios for PTV#1 and PTV#2 abnormalities in
      association with the PTS compared to asymptomatic limbs were 2.52 (95% CI 0.87 to
      7.31) and 4.13 (95% CI 1.30 to 13.11). In conclusion, residual venous
      abnormalities after DVT are common and when present in the popliteal and tibial
      veins are associated with an increased likelihood of PTS expression.

PMID- 8739532
TI  - Three-dimensional time-of-flight MR angiography and MR imaging versus
      conventional angiography in carotid artery dissections.
AB  - A retrospective analysis comparing the three-dimensional time-of-flight MR
      angiography, MR imaging and transfemoral digital substraction angiography (DSA)
      in cases of carotid artery dissection was made. During a 2-year period, 12 cases
      (11 males and 1 female), aged between 16 and 60 years, were submitted to our
      Hospital with the symptoms of TIA, stroke or cranial nerve palsies and the
      suspicion of carotid dissection. Transfemoral angiograms were done in other
      Institutions, while the MRI and MRA were performed in our diagnostic center.
      Blind interpretation of MR and angiography images was made by two independent
      radiologists. MR angiography in combination with MR imaging was more accurate
      than conventional angiography in the diagnosis of carotid artery dissection.
      Respective sensitivity and specificity were 100% and 100% for MRI with MRA and
      91.6% and 100% for conventional angiography. From the analysis of this small
      series, we can conclude that MR angiography in combination with MR imaging is a
      reliable noninvasive method for use in diagnosis of extracranial internal carotid
      artery dissection.

PMID- 8739533
TI  - A clinicopathological study of familial abdominal aortic aneurysms.
AB  - The purpose of this report is to document what we have observed in patients with
      familial abdominal aortic aneurysms (FAAAs) between 1987 and 1993. Patients with
      FAAAs were reviewed and compared with those without familial clustering with
      regard to age, sex, past history, laboratory data, smoking habits, and type of
      implanted graft. We identified 7 families among which a total of 15 members had
      AAAs. The incidence of familial clustering reached 5.4%. The mean age of the FAAA
      group was significantly younger than that of the non-FAAA group (mean age: 65.8
      +/- 10.3 versus 71.0 +/- 7.3 years). In the FAAA group, furthermore, patients in
      the second generation were significantly younger than those in the first
      generation (mean age: 55.3 +/- 10.5 versus 69.6 +/- 7.4 years). FAAA was
      significantly more often complicated by ischemic cardiac diseases. There were no
      significant differences in other risk factors. Interestingly, however, we
      observed a morphological similarity in the shape of the aneurysms within each
      family. Histological examinations showed moderate or severe lymphocytic
      infiltration into the aortic adventitia in 6 out of 9 cases. FAAA is clinically
      important, because it can represent a high-risk group that may benefit from a
      screening program for early detection and elective management of AAA. Studies of
      FAAAs will be useful for elucidating the pathogenesis of AAAs.

PMID- 8739534
TI  - Peripheral microcirculatory blood flow in haemodialysis patients treated with
      erythropoietin.
AB  - BACKGROUND: Haemodialysis patients have abnormal blood vessels, and increased
      morbidity from vascular causes, effects which may potentially be enhanced by
      erythropoietin (EPO) therapy. METHODS: Microcirculatory blood flow was assessed
      using a laser-Doppler flowmeter in a group of 19 haemodialysis patients before
      and during treatment with recombinant human (EPO). RESULTS: Haemodialysis
      patients had significantly impaired microcirculatory blood flow under both basal
      (25 degrees C) and hyperaemic (44 degrees C) conditions by comparison with 19
      normal controls (baseline flow, median and range: patients 1.54 (0.28-2.54)
      volts, controls 3.39 (0.94-5.23) volts, p < 0.001 Mann Whitney U Test; hyperaemic
      flow, patients 2.69 (1.08-3.82) volts, controls 3.81 (1.32-8.00) volts, p <
      0.001). There was no significant influence on microcirculatory blood flow of
      patient age, duration of haemodialysis, short-term EPO therapy (subcutaneous or
      intravenous), therapy with a calcium-channel blocker/vasodilator (nifedipine), or
      radiological evidence of vascular calcification. CONCLUSIONS: Haemodialysis
      patients have an abnormal peripheral microvasculature, which may be relevant to
      their increased risk of ischaemic tissue damage and poor wound healing.

PMID- 8739535
TI  - Physical and pharmacologic manipulation of the vascular system as measured by the
      release of TFPI and other mediators of antithrombotic actions.
AB  - Utilizing highly sensitive monoclonal based assays, we have measured various
      mediators of antithrombotic action including t-PA, prostacyclin and tissue factor
      pathway inhibitor (TFPI). To evaluate the pharmacologic stimulation of these
      mediators, blood from patients treated with heparin and low molecular weight
      heparin in (LMWH) at various dosages, group of patients treated with oral
      polydeoxyribonucleotide (defibrotide), a synthetic analogue of heparin, namely
      aprosulate (Luitpold Pharma, Munich, Germany) were analyzed for various vascular
      mediators. Similarly, to evaluate patients treated with physical modalities such
      as the sequential compression devices alone and sequential compression devices in
      combination with LMWHs were tested for these same parameters. Heparin produced a
      marked release of TFPI and t-PA after i.v. administration. After subcutaneous
      administration, a relatively smaller elevation of these parameters were seen.
      Several of the LMWHs produced varying effects on the release of TFPI and t-PA and
      the area under the curve after the s.c. injection was found to be much higher
      than i.v. administration. Defibrotide administration after i.v. and oral
      administration also resulted in a significant increase in the TFPI and t-PA
      antigen levels. However, the prostacyclin metabolite 6-keto-PGF1 alpha was much
      higher than the values obtained the heparins. Repeated administration of a
      hypersulfated heparin analogue produced marked increase in TFPI in both i.v. and
      s.c. studies. These results indicate that besides directly acting on plasmatic
      mediators, antithrombotic drugs are capable of releasing endogenous mediators of
      antithrombotic actions. Physical manipulation of the vascular system can also
      produce these effects. Thus, both physical and pharmacologic means can be used to
      produce an antithrombotic state to mediate their prophylactic and therapeutic
      effects.

PMID- 8739536
TI  - Inhibited cold-induced vasodilatation in patients with vibration-induced white
      finger.
AB  - We investigated cold induced vasodilatation in 37 vibration-exposed men without
      vibration-induced white finger (VWF) and 20 men with VWF. The left third finger
      was dipped into a cooling box and was cooled with cold air of 5 degrees C for 15
      min. Finger skin blood flow during the cold stimulus was measured using the laser
      Doppler method. We observed that cold-induced vasodilatation was inhibited in
      patients with VWF and the cold air test was relatively useful for diagnosis VWF.

PMID- 8739537
TI  - Pharmacological control of intimal hyperplasia in small diameter
      polytetrafluoroethylene grafts. An experimental study.
AB  - OBJECTIVE: The efficacy of a postoperative treatment with Low molecular weight
      heparin (LMWH) vs Ticlopidine in controlling early thrombosis, intimal
      hyperplasia and growth of true endothelial cells in small prosthetic expanded
      polytetrafluoroethylene (ePTFE) grafts (4 mm) interposed in the carotid artery of
      sheep has been evaluated. EXPERIMENTAL DESIGN: Thirty animals were randomized
      into three different groups: control group (CTRL); ticlopidine hydrochloride
      (TICL) 250 mg/b.d. by month for 4 weeks from day 1; LMWH 3,085 IU AXa s.c.
      preoperatively and once a day for the same period. RESULTS: Complete thrombosis
      of the graft occurred in 7 sheep in the CTRL group and 5 in the TICL group while
      2 partial thrombosis were observed in the LMWH group (n.s.). In all the evaluable
      cases, hyperplasia was observed in both anastomotic areas and did not involve the
      middle portion of the graft. The mean +/- SD intimal thickness was 603 +/- 20
      micron in the CTRL group, 356 +/- 10 in the TICL group and 152 +/- 17 in the LMWH
      group (p < 0.001) compared to the 60 +/- 12 of the normal intima. True endothlial
      cells were found mainly in the LMWH group close to the arterial anastomosis.
      CONCLUSIONS: The postoperative use of LMWH seems to inhibit intimal hyperplasia,
      with interesting results also on patency and cellular coverage. Further studies
      are necessary to support this promising trend.

PMID- 8739538
TI  - Patterns of atherosclerotic occlusive disease of lower leg and pedal arteries in
      hypertensive patients undergoing infrainguinal bypass procedures.
AB  - OBJECTIVE: To analyse the atherosclerotic involvement of lower leg and foot
      arteries in patients undergoing infrainguinal bypass grafting. SETTING:
      Department of Surgery, University Hospital. PATIENTS: Among 282 limbs (267
      patients), fifty limbs belonged to hypertensive nondiabetics (Group A), 39 to
      hypertensive diabetics (Group B), 129 to normotensive nondiabetics (Group C) and
      64 to normotensive diabetics (Group D). INTERVENTIONS: Femoropopliteal or
      femorodistal bypass procedures. MEASURES: Intraoperative postreconstruction
      serial angiography of the lower leg and foot arteries. RESULTS: Occlusion rate of
      two or three lower leg arteries was significantly higher among diabetics (Group B
      77% and Group D 73%, respectively) compared to nondiabetics (Group A 56% and
      Group D 51%, respectively). It was similar in diabetic patients with or without
      hypertension. The incidence of having both foot arches (dorsal and plantar arch)
      intact was significantly higher in nondiabetic patients with hypertension (Group
      A). Only 5.8% of these patients demonstrated both deficient or occluded foot
      arches compared to 18% in Group B and 31% in Group C and 20% in Group D.
      CONCLUSION: Hypertension does not seem to contribute to the extent and severity
      of lower leg and foot vessel involvement in patients undergoing infrainguinal
      bypass surgery.

PMID- 8739539
TI  - Effects of the lazaroid U74389G (21 aminosteroid) on skeletal muscle reperfusion
      injury in rabbits.
AB  - The purpose of this experiment was to evaluate the effects of the aminosteroid
      U74389G on skeletal muscle reperfusion injury in rabbits. In 24 white New Zealand
      rabbits (weighing 7.0-8.0 lb), the rectus femoris muscle on both sides was
      completely isolated on a single vascular pedicle (artery and vein) and a major
      accessory vein. All muscles were weighed using a suspension spring balance and
      then underwent 4 hours of normothermic ischemia followed by 24 hours of
      reperfusion. Muscle ischemia was induced by the application of atraumatic
      vascular clamps to the vascular pedicles. Complete muscle ischemia and
      reperfusion were documented by a laser flow meter. The animals were divided into
      three groups; Group I (n = 8) served as control, Group II (n = 8) received an
      i.v. bolus of U74389G (1.5 mg/kg) five minutes prior to ischemia, Group III (n =
      8) was given the same dose of lazaroid five minutes prior to reperfusion. Muscle
      biopsies were obtained before ischemia and after reperfusion for quantification
      of myeloperoxidase (MPO) activity. At the completion of reperfusion, the muscles
      were excised, weighed and cut into slices along the longitudinal axis and then
      incubated for 30 minutes in 0.05% nitroblue tetrazolium. Areas of necrosis were
      determined by computerized planimetry. The following results indicate that
      reperfusion muscle necrosis in rabbits is significantly decreased by the
      administration of the lazaroid U74389G. Leukocyte sequestration was not affected
      by the lazaroid administration. These beneficial effects were observed whether
      the lazaroid was administered prior to ischemia or prior to reperfusion and were
      independent of leukocyte sequestration.

PMID- 8739540
TI  - Low molecular weight heparins in the initial treatment of deep vein thrombosis.
AB  - All major trials to-date provide strong evidence that, for the initial treatment
      of DVT, adjusted-dose LMWHs are at least as effective and safe as unfractionated
      heparin (UFH). When compared with UFH, LMWHs achieved better thrombus lysis and
      had less bleeding complications (21-91% risk reduction) and mortality (51%
      reduction). They also reduced the incidence of recurrent DVT and PE at 90 days
      follow-up while there was no need for monitoring. Despite these exciting findings
      however, long-term evaluation of mortality rate, recurrent venous
      thromboembolism, blood monitoring tests efficacy and thrombus
      propagation/reduction are open issues. Furthermore, venous haemodynamics have
      never been tested. There is an ongoing Canadian study today, aiming to determine
      LMWHs effectiveness in reducing death, recurrent venous thromboembolism and
      haemorrhagic complications; it is obvious however that further studies are
      needed. We must determine if a prolonged use of LMWHs (i.e. 90 days) is more
      effective in preventing the post-thrombotic sequelae, reducing also the incidence
      of haemorrhagic complications; we also need to know the nature of the
      haematological changes that develop and the relationship between these changes
      and the recurrence rate; and finally, we must identify effective blood tests to
      monitor this treatment.

PMID- 8739541
TI  - Efficacy and clinical tolerance of parenteral pentoxifylline in the treatment of
      critical lower limb ischemia. A placebo controlled multicenter study. Norwegian
      Pentoxifylline Multicenter Trial Group.
AB  - A total of 114 patients with critical lower limb ischemia from 11 hospitals were
      randomized to either Pentoxifylline 600 mg or placebo given intravenously twice a
      day. Rest pain was evaluated both by the investigator and the patient. Pain was
      evaluated with the patient in the supine as well as in the sitting position using
      a pain score scale, a pain relief scale and a visual analogue scale. All patients
      underwent a clinical examination, measurement of ankle systolic blood pressure
      and arteriography. These arteriograms were evaluated by a radiologist who did not
      know which treatment had been given. If no beneficial effect of the treatment was
      observed after one week, further medication was discontinued. Otherwise the
      treatment continued for two additional weeks. There was no statistically
      significant difference in pain-free or absolute walking distance between the two
      groups. Evaluating the patients with the most pronounced amelioration of rest
      pain in the supine position (divided by 4 to divided by 2 points), there was a
      beneficial effect of Pentoxifylline compared to placebo. Evaluation of the total
      material did not, however, show any statistical significances between the groups.
      From further subgroup analysis excluding patients who had only slight pain at the
      entrance of the study, there was a significant improvement in rest pain in favour
      of Pentoxifylline following seven days of treatment. In this group the pain
      evaluated according to this visual analogue scale had decreased 37 points (54%)
      compared to 14 points (25%) in the placebo group. More side effects, mainly
      gastrointestinal, were observed in the Pentoxifylline group. Most of these could
      be eliminated by increasing the infusion time. Further investigations are
      necessary to evaluated the place of Pentoxifylline in the treatment of patients
      with critical limb ischemia.

PMID- 8739542
TI  - Why we need the Cochrane Collaboration.

PMID- 8739543
TI  - Non-psychostimulant drugs of abuse and anxiogenic drugs activate with
      differential selectivity dopamine transmission in the nucleus accumbens and in
      the medial prefrontal cortex of the rat.
AB  - In rats vertically implanted with concentric dialysis probes in the medial
      prefrontal cortex and in the medial nucleus accumbens, morphine, ethanol and
      nicotine failed to modify extracellular dopamine in the medial prefrontal cortex
      at doses that were fully effective in raising extracellular dopamine in the
      nucleus accumbens. Conversely, the aversive/anxiogenic drugs picrotoxin,
      pentylenetetrazol and FG 7142, administered at subconvulsant doses, increased
      extracellular dopamine in the medial prefrontal cortex but failed to do so in the
      nucleus accumbens. Systemic administration of low doses of the 5HT3 antagonist
      ICS 205930, previously reported to prevent the increase of extracellular dopamine
      in the nucleus accumbens elicited by morphine, nicotine, ethanol and haloperidol
      (Carboni et al. 1989) as well as by stress (Imperato et al. 1990), also prevented
      the increase of extracellular dopamine elicited in the prefrontal cortex by
      anxiogenic drugs. Therefore, mesocortical and mesolimbic dopamine neurons show
      clear-cut differences in the reactivity to drugs of abuse and to aversive drugs
      but are both modulated by a facilitatory serotonergic input mediated by 5HT3
      receptors.

PMID- 8739544
TI  - Repeated administration of cocaethylene induces context-dependent sensitization
      to its locomotor effects.
AB  - The cocaine analog, cocaethylene, has recently been identified as an active
      metabolite in humans consuming ethanol and cocaine. Since this compound exhibits
      affinity for the dopamine transporter that is more selective than that of
      cocaine, it is conceivable that its behavioral properties may be distinguishable
      from those of cocaine (cf. Elsworth et al. 1993). To investigate further the
      behavioral effects of cocaethylene, its ability to induce sensitization to
      locomotor activity in C57BL/6 mice was determined and compared with that of
      cocaine. In the first part of the study, mice were treated repeatedly with
      cocaethylene in the test environment and were then challenged with several
      different doses of the same drug. Repeated administration of 10, 20 or 40 mg/kg
      cocaethylene (IP) for 3 consecutive days produced leftward and upward shifts of
      the cocaethylene (2.5-56.6 mg/kg, IP) dose-effect curve on day 4. In the second
      part of the study, mice were treated with 20 mg/kg cocaethylene for 3 days, but
      were immediately placed back in their home cage following the injection: repeated
      administration of cocaethylene for 3 consecutive days did not significantly
      affect the dose-effect curve of cocaethylene (2.5-40 mg/kg, IP) on day 4. In the
      same paradigm, repeated administration of 20 mg/kg cocaine for 3 consecutive days
      produced a significant leftward shift of the cocaine (2.5-56.6 mg/kg, IP) dose
      effect curve on day 4. These results confirm that cocaethylene shares a number of
      properties with cocaine, but also suggest that the drugs are not identical.

PMID- 8739545
TI  - Effects of the putative dopamine D3 receptor agonist 7-OH-DPAT in rhesus monkeys
      trained to discriminate cocaine from saline.
AB  - These studies were designed to evaluate the effects of the putative dopamine D3
      receptor agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetraline (7-OH-DPAT), alone
      and in combination with cocaine, in four rhesus monkeys trained to discriminate
      cocaine (0.4 mg/kg, IM) from saline under a fixed-ratio 30 schedule of food
      presentation. Under these conditions, cumulative doses of cocaine (0.013-1.3
      mg/kg) produced a dose-dependent and complete generalization to the training dose
      of cocaine in all monkeys, while producing only minimal effects on response
      rates. The discriminative stimulus effects of cocaine were antagonized by the non
      selective dopamine receptor antagonist flupenthixol (0.018 mg/kg, IM) in all four
      monkeys. The effects of 7-OH-DPAT (0.01-1.8 mg/kg) were inconsistent across
      monkeys. In two of the four monkeys (monkeys L990 and L958), 7-OH-DPAT
      consistently and completely generalized to cocaine and decreased response rates
      in a dose-dependent manner. Both the cocaine-like discriminative stimulus effects
      and rate-decreasing effects of 7-OH-DPAT were antagonized by flupenthixol in
      these two monkeys. Pretreatment with low doses of 7-OH-DPAT (0.01-0.032 mg/kg)
      had no effect on the cocaine dose-effect curve in monkeys L990 and L958; however,
      higher doses of 7-OH-DPAT (0.032-0.32 mg/kg) shifted the cocaine dose-effect
      curve to the left. In the other two monkeys (monkeys 150F and 89B036), 7-OH-DPAT
      produced a dose-dependent decrease in response rates but did not consistently
      generalize to cocaine. Flupenthixol did not antagonize the rate-decreasing
      effects of 7-OH-DPAT in these two monkeys, and pretreatment with 7-OH-DPAT (0.1
      0.32 mg/kg) produced a decrease in response rates but had no effect on the
      cocaine dose-effect curve. Time-course experiments revealed that 7-OH-DPAT (0.32
      mg/kg) displayed a slower onset and a longer duration of effect than the training
      dose of cocaine. Finally, the D3/D2 dopamine agonist quinpirole completely
      generalized to cocaine in three monkeys, and partially in the fourth monkey.
      Quinpirole showed the highest potency in those monkeys in which 7-OH-DPAT
      consistently generalized to cocaine. The results of the present study suggest
      that, in rhesus monkeys, 7-OH-DPAT produces cocaine-like effects and may modulate
      the discriminative stimulus effects of cocaine in some monkeys.

PMID- 8739546
TI  - Effects of the cannabinoid CB1 receptor antagonist SR141716A on the behavior of
      pigeons and rats.
AB  - SR141716A (Sanofi Recherche), a pyrazole derivative with high affinity for rat
      and human CB1 cannabinoid receptors, has recently been reported to reverse
      biochemical, physiological and behavioral effects induced by cannabinoid
      agonists. The present experiments characterized the activity of SR141716A (SR) in
      behavioral procedures designed to assess its antagonistic and intrinsic effects
      on unconditioned behavior and on complex learned behaviors. Six adult male
      pigeons were trained to discriminate injections of 0.56 mg/kg delta 9
      tetrahydrocannabinol (delta 9-THC) from vehicle under a two-key, fixed-ratio
      schedule of food reinforcement. SR (IM) produced a nearly complete blockade of
      THC-appropriate responding occasioned by the training dose without inducing
      significant changes in session response rates, but also produced partial
      substitution for delta 9-THC when administered alone. In another group of pigeons
      trained under a multiple schedule of signaled and unsignaled fixed consecutive
      number (FCN) responding, SR had little effect on accuracy, but delta 9-THC
      produced dose-related decreases in accuracy under both schedule components. SR
      was also evaluated in acoustic startle procedures in rats. SR produced little
      effect either on startle amplitude or prepulse inhibition of acoustic startle. In
      contrast, the potent cannabinomimetic CP-55, 940 produced large decreases in
      startle responses elicited by 120 dB [A] broad-band noise. These decreases were
      completely reversed by SR (10 mg/kg, IP). In concurrent measures, SR blocked the
      hypothermic effect CP-55,940. These results suggest that SR is an effective
      antagonist of the psychoactive effects of cannabinoids.

PMID- 8739547
TI  - Relationship between up-regulation of nicotine binding sites in rat brain and
      delayed cognitive enhancement observed after chronic or acute nicotinic receptor
      stimulation.
AB  - (-)-Nicotine tartrate (2 mg/kg), and a nicotinic agonist, RJR 2403 (1.4 mg/kg),
      and antagonist, mecamylamine (1 mg/kg), were administered to separate groups of
      rats SC twice daily for 10 days. Two other groups received the same doses of
      nicotine or RJR 2403 for 1 day followed by saline for 9 days. Twenty-four hours
      after the final injection, the rats were compared to a 10-day saline-injected
      group on acquisition of a hidden platform position in the Morris water maze (20
      trials, 30-min inter-trial interval). The rats were killed 48 h after the last
      drug injection and frontal, entorhinal and posterior cingulate cortex and dorsal
      and ventral hippocampus assayed for [3H]-nicotine binding density. Chronic
      nicotine significantly increased the number of frontal and entorhinal cortical
      and dorsal hippocampal, but not posterior cingulate cortical or ventral
      hippocampal, nicotinic receptors, and improved rate of learning. Chronic
      mecamylamine and RJR 2403 also significantly increased the number of nicotinic
      receptors in frontal cortex, though not other regions, but retarded rate of
      learning. Nicotine given for 1 day 11 days earlier marginally increased nicotinic
      receptors in entorhinal cortex (but not other regions) and significantly
      increased rate of learning, though significantly less than 10-day nicotine.
      Entorhinal cortical and dorsal hippocampal nicotinic receptor numbers were
      positively associated with rate of learning but not performance at asymptote.
      Thus cognitive enhancement after chronic nicotine is in part a delayed
      consequence of nicotine administration 11 days earlier, and may reflect regional
      changes in nicotinic receptor up-regulation.

PMID- 8739548
TI  - Inbred mouse strains vary in oral self-selection of nicotine.
AB  - Inbred mouse strains differ in sensitivity to a first dose of nicotine and in the
      development of tolerance to nicotine. The experiments reported here used six
      inbred mouse strains (A, BUB, C3H, C57BL/6, DBA/2, ST/b) that differ in
      sensitivity to an acute challenge dose of nicotine to determine whether
      differences in oral self-selection of nicotine exist. Animals were presented with
      solutions containing nicotine or vehicle (water or 0.2% saccharin) and their
      daily intake of the two fluids was measured for 4 days starting with a 10
      micrograms/ml nicotine solution. This was followed by sequential 4-day testing
      with 20, 35, 50, 65, 80, 100, 125, 160 and 200 micrograms/ml nicotine solutions.
      The strains differed dramatically in their self-selection of nicotine and in
      maximal daily dose (mg/kg); the rank order of the strains was C57BL/6 > DBA > BUB
      > A > or = C3H > or = ST/b for both the tap water and 0.2% saccharin choice
      experiments. Correlations between nicotine consumption and sensitivity to
      nicotine, as measured by a battery of behavioral and physiological responses,
      were also calculated. Strain differences in nicotine intake were highly
      correlated with sensitivity to nicotine-induced seizures. As sensitivity to
      nicotine-induced seizures increases, oral self-selection of nicotine decreases.
      This finding may suggest that this toxic action of nicotine serves to limit
      intake.

PMID- 8739549
TI  - Ethanol-like discriminative stimulus effects of the neurosteroid 3 alpha-hydroxy
      5 alpha-pregnan-20-one in female Macaca fascicularis monkeys.
AB  - The present study was designed to characterize the discriminative stimulus
      effects of ethanol and the neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one
      (allopregnanolone) in non-human primates. Female cynomolgus monkeys (Macaca
      fascicularis) were trained in a two-lever procedure to discriminate 1.0 g/kg
      ethanol (IG, 30 min pretreatment) from water using food reinforcement. Consistent
      with previous results in a variety of species, pentobarbital (0.56-17 mg/kg, IG)
      resulted in a dose-dependent substitution for the discriminative stimulus effects
      of ethanol, with an average ED50 value of 1.9 mg/kg. Administration of
      allopregnanolone (0.3-5.6 mg/kg, IV) also produced complete substitution for the
      discriminative stimulus effects of ethanol, with an ED50 value of 1.0 mg/kg.
      Plasma allopregnanolone levels 35 min following the administration of 3.0 mg/kg
      allopregnanolone ranged from 33 to 69 ng/ml. The ethanol-like discriminative
      stimulus effects of 1.0 mg/kg allopregnanolone (IV) were present for 60 min, with
      a return to complete water-appropriate responding at 90 min post-treatment. The
      results indicate that the endogenous neuroactive steroid allopregnanolone
      produces subjective effects in cynomolgus monkeys that are similar to ethanol.
      These findings suggest that changes in the endogenous levels of allopregnanolone
      could alter sensitivity to the subjective effects of ethanol.

PMID- 8739550
TI  - Alpha 2-adrenoceptor antagonists potentiate acetylcholinesterase inhibitor
      effects on passive avoidance learning in the rat.
AB  - The cholinergic hypothesis of Alzheimer's disease (AD) has strongly influenced
      research on learning and memory over the last decade. However, there has been
      limited success treating AD dementia with cholinomimetics. Furthermore, there are
      indications that other neurotransmitter systems affected by this disease may be
      involved in cognitive processes. Animal studies have suggested that
      norepinephrine and acetylcholine may interact in learning and memory. The current
      experiments investigate this interaction in a step-down passive avoidance
      paradigm after coadministration of acetylcholinesterase inhibitors and alpha 2
      adrenoceptor antagonists. Administration of acetylcholinesterase inhibitors
      heptylphysostigmine (0.625-5.0 mg/kg, IP), tacrine (2.5-10.0 mg/kg, PO),
      velnacrine (0.312-2.5 mg/kg, SC), and galanthamine (0.312-2.5 mg/kg IP) each
      enhanced retention of a passive avoidance response at selected moderate doses
      administered 30-60 min prior to training. The alpha 2-adrenoceptor antagonists
      idazoxan (0.312-2.5 mg/kg, IP), yohimbine (0.078-0.312 mg/kg, IP) and P86 7480
      (0.156-0.625 mg/kg, IP) alone failed to enhance learning in this paradigm.
      Coadministration of a subthreshold dose of heptylphysostigmine (0.625 mg/kg, IP)
      with doses of idazoxan, yohimbine or P86 7480 enhanced passive avoidance
      learning. This synergistic interaction may represent effects of antagonism of
      presynaptic alpha 2-adrenoceptor since coadministration of heptylphysostigmine
      and the selective postsynaptic alpha 2-adrenoceptor antagonist SKF 104856 did not
      result in enhanced learning. Taken together these data suggest noradrenergic
      activation through pre-synaptic alpha 2-adrenoceptor blockade may potentiate
      cholinergic activity in the formation of a long-term memory trace. These
      observations may have implications for the treatment of AD with cholinergic and
      adrenergic agents.

PMID- 8739552
TI  - Loss of tolerance to morphine after a change in route of administration: control
      of within-session tolerance by interoceptive conditioned stimuli.
AB  - Tolerance to morphine analgesia (tail-immersion test) was examined after
      manipulation of two aspects of a tolerance test: 1) the route of drug
      administration and 2) the time interval between the test dosing and the tolerance
      test. The intravenous (IV) and intraperitoneal (IP) routes were used, together
      with a novel test for tolerance in which the test morphine was infused IV just 2
      min before measuring the opiate effect. The first experiment validated this test
      as an assay for tolerance by examining the log dose-response (LDR) curve changes
      produced by daily IP injection with 0, 20 or 200 mg/kg morphine; the IV test
      confirmed the expected parallel shift to the right and flattening of the LDR
      curve. In the second experiment, all rats of two groups were injected once daily
      for 3 weeks with 20 mg/kg morphine and with saline except that one group received
      the morphine IV (and saline IP), the other morphine IP (saline IV). The results
      indicated route-specific tolerance. On a test using 20 mg/kg given IV morphine,
      tolerance was significantly greater in rats treated with IV morphine than in
      those treated IP. However, a larger effect on tolerance was produced by a pretest
      application of 5 mg/kg morphine 30 min before the actual tolerance test. This
      manipulation was designed to "prime" short-term, adaptive processes hypothesized
      to occur within a normal tolerance test session as morphine is taking effect. The
      tolerance on the test increased (equivalent to 2 to 3 fold shift in the LDR
      curve) when the pretest morphine was given with the same route as the chronic
      morphine, regardless of treatment group. It was concluded that opiate tolerance
      may be modulated by conditioned stimuli produced by morphine acting through
      different routes. These interoceptive cues appear to modulate rapidly acquired
      and short-lived adaptive processes taking place within a given test session.

PMID- 8739551
TI  - Ethological analysis of cholecystokinin (CCKA and CCKB) receptor ligands in the
      elevated plus-maze test of anxiety in mice.
AB  - The literature on the effects of CCK receptor manipulations in animal models of
      anxiety is rife with inconsistency, and the data subject to a variety of
      methodological and interpretative difficulties. In the present paper, the effects
      of a range of CCK receptor ligands on anxiety in male mice have been assessed
      using an ethological version of the elevated plus-maze test. Compounds selected
      for study were the agonists, CCK-4 and CCK-8s (12.5-100 micrograms/kg), and the
      antagonists, devazepide, L-365, 260 and PD 135158 (1.0 microgram/kg-1.0 mg/kg).
      CCK-4 failed to produce any significant behavioural effects over the dose range
      tested, while treatment with the sulphated octapeptide, CCK-8s, induced signs of
      behavioural inhibition at 100 microgram/kg without altering anxiety-related
      indices. Furthermore, in contrast to the clear anxiolytic profile of diazepam (1
      mg/kg), and despite the comprehensive behavioural profiles yielded by ethological
      analysis, all three CCK receptor antagonists studied (devazepide, L-365, 260 and
      PD 135158) were found to be without significant effect under present test
      conditions. Together, present findings provide little support for the involvement
      of CCK receptor mechanisms in anxiety and, in particular, the form of anxiety
      evoked in mice by exposure to a plus-maze.

PMID- 8739553
TI  - Diurnal and weekly variation of tardive dyskinesia measured by digital image
      processing.
AB  - The diurnal and weekly variability of tardive dyskinesia (TD) was assessed
      instrumentally by digital image processing. Weekly assessments were obtained in
      ten patients over a 6-week period. In six of the ten patients, assessments were
      obtained four times over a single 12-h period. Results indicate that TD movements
      measured by instrumental assessment vary from week to week and throughout the
      day. Factors that appear to have affected the variability were changes in
      medications and the time of day when the assessments were conducted.

PMID- 8739554
TI  - Paroxetine treatment and the prolactin response to sumatriptan.
AB  - We studied the effect of the selective serotonin re-uptake inhibitor (SSRI),
      paroxetine (20 mg daily for 16 days) on the neuroendocrine, cardiovascular,
      thermic and subjective responses to the 5-HT1D receptor agonist, sumatriptan (6
      mg, SC). Compared to placebo injection, sumatriptan lowered plasma prolactin and
      oral temperature and increased diastolic blood pressure. While paroxetine
      increased baseline prolactin concentration, it had no effect on any of the
      responses to sumatriptan. In addition, paroxetine did not alter concentrations of
      sumatriptan in plasma. No adverse reactions resulted from the combination of
      sumatriptan and paroxetine. Our findings suggest that combined treatment with
      sumatriptan and paroxetine in the doses used in this study is not necessarily
      contra-indicated. In addition, short-term SSRI treatment may not desensitise 5
      HT1D autoreceptors in humans.

PMID- 8739555
TI  - The memory-facilitating effects of the competitive NMDA-receptor antagonist CGP
      37849 are steroid-sensitive, whereas its memory-impairing effects are not.
AB  - The retention performance of mice in a passive-avoidance task was facilitated by
      low doses (0.3 mg/kg) of the competitive NMDA-receptor blocker CGP 37849, but
      impaired by high doses (30 mg/kg). The facilitatory effect was selectively
      suppressed by elevation of the plasma levels of aldosterone or corticosterone, or
      by blockade of steroid biosynthesis or the mineralocorticoid receptors. The
      impairment of memory, on the other hand, was not steroid sensitive. Accordingly,
      the data are in line with the hypothesis that drug induced memory facilitation is
      dependent on steroid sensitive processes.

PMID- 8739556
TI  - Distribution of keratan sulphate and chondroitin sulphate in wild type and white
      mutant axolotl embryos during neural crest cell migration.
AB  - In embryos of the white mutant axolotl, prospective pigment cells are unable to
      migrate from the neural crest (NC) due to a deficiency in the subepidermal
      extracellular matrix (ECM). This raises the question of the molecular nature of
      this functional defect. Some PGs can inhibit cell migration on ECM molecules in
      vitro, and an excess of this class of molecules in the migratory pathways of
      neural crest cells might cause the restricted migration of prospective pigment
      cells seen in the white mutant embryo. In the present study, we use several
      monoclonal antibodies against epitopes on keratan sulphate (KS) and chondroitin
      sulphate (CS) and LM immunofluorescence to examine the distribution of these
      glycosaminoglycans at initial (stage 30) and advanced (stage 35) stages of neural
      crest cell migration. Most KS epitopes are more widely distributed in the white
      mutant than in the wild type embryo, whereas CS epitopes show very similar
      distributions in mutant and wild type embryos. This is confirmed quantitatively
      by immunoblotting: certain KS epitopes are more abundant in the white mutant. TEM
      immunogold staining reveals that KS as well as CS are present both in the basal
      lamina and in the interstitial ECM in both types of embryos. It remains to be
      investigated whether the abundance of certain KS epitopes in the white mutant
      embryo might contribute to the deficiency in supporting pigment cell migration
      shown by its ECM.

PMID- 8739557
TI  - Effects of extracellular matrix molecules on subepidermal neural crest cell
      migration in wild type and white mutant (dd) axolotl embryos.
AB  - Migration of neural crest (NC) derived pigment cells is restricted in the white
      mutant (dd) axolotl embryo (Ambystoma mexicanum). Transplantations between mutant
      and wild type embryos show that the extracellular matrix (ECM) of the white
      mutant is unable to support the migration of prospective pigment cells in wild
      type embryos (Lofberg et al., 1989, Dev. Biol. 131:168-181). In the present
      study, we test the effects of various purified ECM molecules on NC cell migration
      in the subepidermal migratory pathway of wild type (D/-) and white mutant (dd)
      axolotl embryos. We adsorbed the ECM molecules onto membrane microcarriers, which
      were then implanted under the epidermis. Fibronectin (FN), tenascin (TN),
      collagens I and VI, and a chick aggrecan stimulated migration in both types of
      embryos. Laminin-nidogen, rat chondrosarcoma aggrecan, and shark aggrecan
      stimulated migration in dd embryos but did not affect migration in D/- embryos.
      Collagen III, fibromodulin and bovine aggrecan had no effect on migration in
      either type of embryo. NC cells did not migrate on control microcarriers, which
      lacked ECM molecules. Some cells observed contacting, and presumably migrating
      on, coated microcarriers could be identified as pigment cells by their
      ultrastructure. Enzymatic digestion in vivo with chondroitinase ABC had no effect
      on NC cell migration. The neutral or stimulatory effect of the aggrecans is
      surprising; when tested in vitro they inhibited NC cell migration. The effect of
      three-dimensionality and other molecules present either in the embryonic ECM or
      in solution may overcome the inhibitory effect of aggrecans.

PMID- 8739558
TI  - Effects of calphostin C, specific PKC inhibitor on TPA-induced normal human
      melanocyte growth, morphology and adhesion.
AB  - Normal human melanocytes, which rarely undergo mitosis in vivo, require many
      growth factors and growth-stimulating agents in vitro, such as basic fibroblast
      growth factor (bFGF) and cyclic adenosine monophosphate-stimulating agents or 12
      0-tetradecanoylphorbol 13-acetate (TPA), to proliferate. TPA, known as a protein
      kinase C (PKC)-activator, supports normal human melanocyte growth and influences
      on melanocyte dendrite formation. We have further confirmed the role of the PKC
      mediated pathway in the TPA-dependent melanocyte functions-i.e., proliferation,
      morphology, and adhesion-using Calphostin C (CPC), a highly specific PKC
      inhibitor. Melanocytes require the continual presence of TPA for growth in
      culture. Addition of 8 nM TPA to the medium increased melanocyte growth by 198.4
      +/- 2.3% of that without TPA. The growth induction by TPA was suppressed by the
      addition of 10 nM CPC at the level comparable to that without TPA without any
      morphological alterations. Significant levels of PKC were detected in melanocytes
      chronically exposed to TPA as determined by Western blotting. A long-term
      exposure to TPA (more than 5 days) resulted in marked reduction of melanocyte
      adhesion to plastic cell culture dishes, both uncoated and coated with type IV
      collagen. By the addition of 10 nM CPC in the adhesion assay, the melanocyte
      adhesion was further inhibited in both conditions. These results indicated the
      critical involvement of PKC activation in the TPA-dependent melanocyte functions.
      Continuous activation of PKC by TPA is implicated in melanocyte growth
      stimulation. TPA also has effects on melanocyte morphology, causing the formation
      of long extended dendrites with little cytoplasm. However, inhibition of PKC
      activation by CPC does not affect the melanocyte morphology, and CPC reduces
      melanocyte adhesion to uncoated or type IV collagen coated plastic cell culture
      dishes.

PMID- 8739559
TI  - Yellow marking and pteridine contents in the integument of albino Armadillidium
      vulgare.
AB  - The albino mutant strain in the woodlice, Armadillidium vulgare, was investigated
      with respect to the yellow patterns on the dorsal integument. Pigment cells were
      observed with electron microscope in order to determine the cell types of yellow
      markings. Quantitative analyses of pteridines in the albino were carried out by
      HPLC. The result indicated that the albino integument contain sepiapterin,
      biopterin, pterin, isoxanthopterin as in the wild type and the red mutant strain.
      The total amount of the four pteridines in the albino was about half as much as
      that in the red phenotype for both males and females, respectively. Males and
      females showed almost the same totals and ratios of the four pteridines in the
      albino and red phenotypes. Therefore, pteridine contents in both phenotypes of A.
      vulgare may not be related to the activity of androgenic gland hormone. Yellow
      chromatophores of the albino and red phenotypes were morphologically identical,
      emitting a yellow fluorescence. These cells contained numerous electron-lucent
      pigment organelles which were similar to pteridine granules of the wild type.

PMID- 8739560
TI  - Genomic organization and FISH mapping of human Pmel 17, the putative silver
      locus.
AB  - The Pmel 17 gene is expressed preferentially in pigment cells. It has been mapped
      to human chromosome 12 pter-q21 and mouse chromosome 10, near the silver locus.
      The Pmel 17 gene contains an insertional mutation at its carboxyl terminus in the
      silver mouse, suggesting that the silver locus might correspond to the gene. In
      the current studies, we have isolated and characterized human Pmel 17 genomic
      clones and employed FISH mapping for a precise localization of this gene in the
      human chromosome. The FISH mapping placed the Pmel 17 gene at human chromosome 12
      q12-q13. The human gene consists of nine exons and eight introns, and the entire
      coding region of the gene spans approximately 7.9 kb of the human chromosome 12.
      The putative functional domains, such as the signal sequence, histidine-rich, 26
      amino acid repeats, cysteinerich, transmembrane and cytoplasmic domains, were
      encoded by separate exons. Cistranscription elements such as a TATA, a CAT and
      other potential elements for pigment cell-specific gene expression were found
      within 1100 base pairs of the 5' flanking region.

PMID- 8739562
TI  - The vitronectin receptor (alpha V beta 3) as an example for the role of integrins
      in T lymphocyte stimulation.
AB  - Integrins are a family of cell surface receptors which mediate the adhesion of
      cells to each other or to extracellular matrix (ECM) proteins. The interaction of
      integrins with their ligands or counter-receptors was initially considered to be
      a one-way process in that cells actively regulate the interaction of integrins
      with their ligands ('inside-out signal'). In contrast, it was not obvious that
      cells would receive a signal from the outside via the integrin heterodimers
      following ligand binding ('outside-in signal'). Recent evidence increasingly
      supports the active role of integrins in cell activation and proliferation. Many
      reports describe the effects of integrin-mediated signaling in lymphoid cells.
      Our studies of gamma/delta T cells, expressing the beta 3 integrin vitronectin
      receptor (VNR), reflect some of the consequences this active interaction between
      lymphocytes and the ECM could have for T cell activation and differentiation. The
      VNR has been described as a T cell costimulatory molecule. We recently reported
      that the VNR has the potential to stimulate cytokine secretion in T cell
      hybridomas without involvement of T cell receptor-mediated signals. Further
      studies demonstrated tyrosine phosphorylation of proteins following VNR cross
      linking and the interaction of the VNR with protein kinases. Intensive research
      focuses on the signal transduction mechanisms of integrins and their interaction
      with other costimulatory or activation molecules. This knowledge is important to
      better understand the role of adhesion molecules, the ECM, and the cellular
      microenvironment for lymphocyte activation and differentiation.

PMID- 8739563
TI  - Involvement of tyrosine phosphorylation in endothelial adhesion molecule
      induction.
AB  - Induction of endothelial adhesion molecules by the cytokine tumor necrosis factor
      alpha (TNF) can occur independently of protein kinase C and activation of a
      protein tyrosine kinase (PTK) has recently been implicated in the upregulation of
      vascular cell adhesion molecule 1 (VCAM-1) by interleukin-4 (IL-4) on endothelial
      cells. We demonstrate that the PTK inhibitors herbimycin A or genistein suppress
      induction of endothelial VCAM-1 and E-selectin, as well as subsequent monocytic
      cell adhesion to endothelial cells stimulated by TNF. Inhibition studies indicate
      that specific tyrosine phosphorylation following PTK activation is involved in
      the mobilization of the transcription factor, nuclear factor kappa B, and VCAM-1
      mRNA expression. This may have implications for pathophysiological conditions
      that involve the upregulation of these molecules (e.g. inflammation and
      atherosclerosis).

PMID- 8739561
TI  - Interleukin-2 and human immunodeficiency virus infection: pathogenic mechanisms
      and potential for immunologic enhancement.
AB  - A hallmark of human immunodeficiency virus (HIV) infection is the progressive
      loss of CD4+ T lymphocytes; however, qualitative defects in immune responses
      occur prior to the precipitous drop CD4+ T cell numbers. One of the first
      immunologic defects to be described in HIV-infected individuals is a deficiency
      in interleukin (IL)-2 production. The addition of IL-2 in vitro to cultures of
      mononuclear cells from HIV-infected individuals partially or completely restored
      certain defective cellular immune responses. However, production of or addition
      of IL-2 has also been associated with increased viral replication in infected T
      cells. These observations underscore the pernicious correlation between immune
      activation and HIV replication. However, recent in vitro and in vivo studies have
      provided promising preliminary results suggesting that, at least at certain
      stages of disease, the benefits of IL-2 mediated immune enhancement may outweigh
      or override the inductive effects of this cytokine on HIV production.

PMID- 8739564
TI  - Immunosuppression through blockade of CD28:B7-mediated costimulatory signals.
AB  - It is now well established that T cells require two signals for activation and
      effector function. The first signal is provided through the T cell receptor for
      antigen. The best-characterized pathway which provides the second, or
      costimulatory, signal is through the CD28 receptor on the surface of T cells. In
      vitro, ligation of the T cell receptor without a second signal induces a long
      lived state of anergy in T cells. CD28 has two known ligands, B7-1 and B7-2,
      expressed on activated antigen-presenting cells. A soluble fusion protein called
      CTLA4Ig has been produced which binds B7-1 and B7-2 and acts as a competitive
      inhibitor of CD28. In vitro and in vivo studies with CTLA4Ig demonstrate that it
      is an extremely effective immunosuppressive agent in models of transplantation
      and autoimmunity. Mechanistic studies indicate that CTLA4Ig may work by partially
      inhibiting the expansion of antigen-reactive cells and inducing anergy in the
      residual population.

PMID- 8739566
TI  - Cellular immune responses of patients with juvenile chronic arthritis to retinal
      antigens and their synthetic peptides.
AB  - The objective of this study was to determine the proliferative responses of
      peripheral blood lymphocytes of ocular antigens like retinal S-antigen, peptides
      M and G of S-antigen, yeast histone H3 peptide 106-121 homologous to peptide M
      and peptide R16 of interphotoreceptor retinoid binding protein (IRBP) in children
      with juvenile chronic arthritis (JCA). We have studied the in vitro proliferative
      response of peripheral blood lymphocytes from 41 patients with JCA (10 with and
      31 without uveitis) and 23 healthy controls against the above antigens. The
      responders were retested after 1 or 6 months. Fifty (5/10) and 9.7% (3/31) of JCA
      patients with and without uveitis, respectively, responded (stimulation index >
      3) to S-antigen or one of its peptide listed above or yeast histone H3 peptide or
      R16 of IRBP. None of the healthy controls responded to any of these antigens. The
      difference in the frequency of responders (SI > 3) between JCA associated with
      uveitis and healthy controls was statistically significant (p = 0.001).
      Similarly, the difference between JCA with and without uveitis was also
      significant (p = 0.013). Our findings suggest that these antigens may have a role
      in the pathogenesis of uveitis in a subset of patients with JCA.

PMID- 8739565
TI  - Graft-versus-host disease and the Th1/Th2 paradigm.
AB  - Graft-versus-host disease (GVHD) is the major complication after allogeneic bone
      marrow transplantation (BMT) and is initiated by alloreactive donor T cells
      recognizing foreign histocompatibility antigens of the host. There is now
      substantial experimental and clinical evidence to implicate a dysregulation of
      cytokine networks as a primary cause for the induction and maintenance of GVHD.
      In this article, current knowledge of the involvement of cytokines in GVHD is
      reviewed. The balance between type 1 cytokines (interleukin-2, interferon-gamma)
      and type 2 cytokines (interleukin-4, interleukin-10) is hypothesized to govern
      the extent to which a cell-mediated immune response and a systemic inflammatory
      response develop after allogeneic BMT. Because type 2 cytokines can inhibit the
      production of the proinflammatory cytokines interleukin-1 and tumor necrosis
      factor-alpha, a type 1 to type 2 shift in the initial response of donor T cells
      to host alloantigens may interrupt the cytokine cascade after allogeneic BMT and
      may offer a new approach to the prevention and treatment of acute GVHD.
      Interventions to specifically eliminate or modify the response of donor T cells
      to alloantigens in order to reduce GVHD may obviate the need for T cell depletion
      in clinical BMT and thus avoid the increased risk of relapse of malignancy and
      impairment of donor cell engraftment.

PMID- 8739567
TI  - Cytokine production pathway in the elderly.
AB  - It is well known that aging is associated with various alterations in lymphoid
      cell functions, particularly with a progressive decline in immune responsiveness
      to exogenous antigens and increasing incidence of autoimmune phenomena. Many
      studies have been focused on the mechanisms of the immunologic features of aging.
      this review describes our results of studies performed to determine the influence
      of age on the capacity to produce interleukin-2 (IL-2), interferon-gamma (IFN
      gamma), interleukin-4 (IL-4), interleukin-t (IL-5), interleukin-6 (IL-6) and
      tumor necrosis factor (TNF). Mitogen-stimulated cultures of mononuclear cells
      (MNC) from human beings were assessed for cytokine-producing capacity. A
      significant decrease in IFN-gamma and IL-2 production by MNC cultures from
      elderly individuals was observed. No significant difference was instead observed
      between cultures from elderly individuals and those from young ones as regards
      TNF-alpha, IL-4 and IL-6 production. Mitogen or antigen-stimulated cultures of
      MNC from aged mice also displayed a significant decrease in IFN-gamma and IL-2
      production as well as TNF-beta. Instead IL-4 and IL-5 production significantly
      increased in these cultures. We suggest that this imbalanced cytokine production
      may well account for the pattern of immune response which may be observed in the
      elderly, i.e. a normal or increased humoral response (including autoimmune
      responses) in face of a low T cell immune responsiveness.

PMID- 8739568
TI  - Lack of effect of NaCl and/or metoclopramide on exogenous (13C)-glucose oxidation
      during exercise.
AB  - The purpose of this study was to compare the oxidation rate of ingested glucose
      during prolonged exercise, without and with the addition of sodium to the
      solution. The effect of metoclopramide, a drug which favors gastric emptying, was
      also investigated since gastric emptying could be a factor limiting the
      bioavailability of ingested glucose. Six subjects performed four bouts of
      exercise of 2 hours each at 64 +/- 4% VO2max on a cycle ergometer during which
      they ingested 100 g of glucose enriched with 13C, without (trials 1 and 3) and
      with (trials 2 and 4) addition of 25 mmol.l(-1) of NaCl. The glucose solution was
      ingested in four equal volumes (175 ml containing 25 g of glucose) at 0, 30, 60
      and 90 min of the exercise period. For the trials 3 and 4, the subjects were
      given 10 mg of metoclopramide orally 60 min before the beginning of exercise. The
      VO2, VCO2 and heart rate were similar in response to exercise between the four
      trials. No significant difference was observed between trials for the oxidation
      rates of ingested glucose during the first as well as the second hour of
      exercise. Over the 120 min of exercise, the amounts of exogenous glucose oxidized
      were 52.0 +/- 9.6, 54.3 +/- 10.9, 52.7 +/- 12.3 and 53.3 +/- 10.4 grams for
      trials 1 to 4, respectively. The contribution of exogenous glucose oxidation to
      the energy yield represented 13.0 +/- 1.8% without and 13.2 +/- 1.9% with
      addition of NaCl. The amounts of endogenous carbohydrate and fat oxidized were
      also similar in the four trials. These results suggest that neither the addition
      of NaCl to glucose solutions nor the ingestion of metoclopramide increases the
      contribution of the oxidation of ingested glucose to the total energy yield
      during prolonged exercise.

PMID- 8739569
TI  - Force development of dynamic and static contractions in children and adults.
AB  - There are still unclarified points remaining in regard to the characteristics of
      force development in children who are immature in their basic activities in daily
      living. Moreover, there are morphological, histological, and biochemical
      differences between immature and mature muscles. In the present study, dynamic
      elbow flexion and static contractions which were performed by elbow flexors with
      maximum effort were examined by force-velocity and force-time relationships and
      electromyograms (EMG) in six-year-old children and in adults. In dynamic
      contractions with various loads, the force-velocity relationship for children was
      (P + 5.65) (v + 1.48) = 19.51, and (P + 14.65) (v + 2.26) = 96.21 for adults. The
      maximum power in children and adults was 22.8 watts and 160.8 watts,
      respectively. The contraction delay in children was greater than that in adults
      for every relative load. In static contractions, the maximum rate of force
      development for children was significantly lower than that for adults at each pre
      tension. With an increase in pre-tension, the adult rate showed a tendency to
      decrease, whereas the rate for children showed no change. The electromechanical
      delay observed in children was significantly greater than that in adults. For
      dynamic and static contractions, the contractile speed in children was lower than
      that in adults.

PMID- 8739570
TI  - Power spectral analysis of RR interval and blood pressure short-term variability
      at rest and during dynamic exercise: comparison between cyclists and controls.
AB  - To determine the adaptations of the autonomic nervous system in the control of
      heart rate and blood pressure induced by endurance training, 10 competitive
      cyclists aged 27 +/- 7 years and 10 age-, weight- and height-matched sedentary
      controls were subjected to Power Spectral Analysis of the RR interval and of
      blood pressure at supine rest and during submaximal cycloergometric exercise test
      in the supine position at 20% and 40% of maximal workload. At rest, the high
      frequency (HF) power of the RR interval was higher in cyclists (p < 0.05)
      compared to controls, whereas the power spectrum of both systolic and diastolic
      blood pressure did not differ between cyclists and controls. During exercise the
      variance, the low-frequency (LF) and the HF power of the RR interval decreased
      significantly (p < 0.005) and similarly in cyclists and controls. The LF/HF ratio
      of the RR interval increased (p < 0.001) and the alfa index of baroreflex
      sensitivity decreased (p < 0.05) without differences between cyclists and
      controls. The variance of both systolic and diastolic blood pressure increased (p
      < 0.001 and p < 0.005, respectively) as well as the HF power of systolic blood
      pressure (p < 0.001) similarly in cyclists and in controls. In conclusion, the
      data of the present study suggest that competitive cycling causes an enhanced
      vagal drive to the sinus node, whereas the neural control of blood pressure is
      not affected. During exercise a vagal withdrawal and a sympathetic activation in
      the neural control of heart rate, together with a reduction of baroreflex
      sensitivity are operative. These changes are similar in cyclists and controls.

PMID- 8739571
TI  - Effect of three hours race walk on energy cost, cardiorespiratory parameters and
      stride duration in elite race walkers.
AB  - The purpose of this study was to quantify changes in energy cost of walking (C),
      ventilation (VE), respiratory frequency (RF), heart rate (HR), expiratory ratio
      (RER), blood lactate concentration (LA), body mass (W) and stride duration (SD)
      after a 3 hour race walk at competition pace in elite race walkers. Subjects were
      tested during 2 submaximal treadmill tests at 12.2 +/- 0.5 km.h(-1) (74.7% VO2max
      speed) before and after a 3 hour overground walk. Significant increases (p <
      0.05) were found in C, HR and significant decreases were found in RER, W, VE
      whereas no changes were observed in LA or SD (means and intra-subject
      variability). However, a wide range of individual coefficients of variation were
      observed for C, VE, RF, HR, SD, W. These results suggest that in well trained
      walkers the energy cost of walking increases with exercise duration but that
      walkers are able to maintain the same stride duration after the test when
      treadmill speed is controlled. Furthermore, some individuals appear to be more
      sensitive to fatigue. Discussion set out a possible effect of substrate
      utilisation changes, thermoregulation or a decrease in mechanical efficiency for
      maintaining the race walk gait apart from the effect of fatigue.

PMID- 8739572
TI  - Unaccustomed high-mileage vs intensity training-related changes in performance
      and serum amino acid levels.
AB  - To test the overtraining-related "imbalanced amino acid hypothesis" (19), the
      influence of an unaccustomed average 103 %.4 wk-1 increase in training mileage
      (ITV) on performance and on serum levels of individual amino acids (AAs) was
      examined in distance runners and controlled by an unaccustomed average 152%.4 wk
      1 increase in tempo-pace and interval runs (ITI). Two mmol.l-1 lactate
      performance (2 LP) increased, 4 LP stagnated and total running distance (TD)
      decreased in the incremental test during ITV--which may indicate an ITV-dependent
      overtraining--in contrast to an ITI-related increase in 2 LP, 4 LP and TD. The
      summed serum AAs decreased in ITV (2744 +/- 534 vs 2933 +/- 663 umol.l-1; p <
      0.05) in contrast to an ITI-related increase (3541 +/- 657 vs 3252 +/- 885 umol.l
      1; p < 0.05) with an average 29% higher final summed AAs concentration during ITI
      (p < 0.05). During ITV 12 individual AAs decreased by 6-17%, 8 remained constant
      and 3 increased (Cys, Met, fTrp) by 6-19%, as opposed to an ITI-related increase
      in 16 AA by 6-55%. The observed ITV-related changes in serum AAs profile were
      smaller than after completing contests as a marathon, a 100 km-run or an ultra
      triathlon. It may be concluded that the observed small changes in AAs profile or
      AAA/BCAA and AA/LNAA ratios only represent an epiphenomenon without recognizable
      influence on incremental test performance, since increases in fTrp/LNAA ratios
      (+28% in ITV vs +45% in ITI) were found to be related both to performance
      impairment (ITV) and improvement (ITI).

PMID- 8739573
TI  - Reliability and comparison of RPE during variable and constant exercise protocols
      performed by older women.
AB  - The purposes of this study were to assess if women 60 to 75 years of age
      perceived a series of exercise intensities differently from selected intensities
      in that series and to determine if a particular intensity was perceived more
      reliably. Twenty-four women (65 +/- 3.8 yr) completed a walking VO2max treadmill
      test. Subjects were either assigned to a variable, randomly ordered exercise
      protocol (GP1) or to one of three constant exercise protocols (Gps2-4). Each
      subject performed relative exercise intensities of 30, 50, and 70% of peak VO2
      for three 5 min work bouts over 3 test days. Differences in RPE (p < 0.05) were
      found between each intensity and between the same intensities from both
      protocols. Women in GP1 rated exercise higher than women who exercised at a
      constant exercise intensity (p < 0.05). Intraclass correlation coefficients
      indicated that the exercise intensity of 50% of maximum was more reliable
      regardless of the protocol (Gp1: R = 0.97, Gp3: r = 0.94). When the RPE-HR
      correlation coefficients were transformed into a log scale, neither protocol had
      a stronger association (p > 0.05) between RPE-HR. It was concluded that older
      women should be given a range of exercise intensities that include the 50%
      relative exercise intensity as a perceptual marker in order to reach a reliable
      rate of exertion.

PMID- 8739574
TI  - Specificity of training and its relation to the performance of distance runners.
AB  - Validated six-month retrospective questionnaires were completed by 119 female and
      234 male coached distance runners (59% compliance) for a descriptive study of
      relationships between specificity of training and best performance in a summer
      season. Runners were aged 26 +/- 10 y (mean +/- SD), specialising in distances
      from 800 m to the marathon, with seasonal best paces of 82 +/- 7% of sex- and age
      group world records. They reported typical weekly durations of interval and
      strength training, and typical weekly durations and paces of moderate and hard
      continuous running, for build-up, precompetition, competition, and
      postcompetition phases of the season. The training programs showed some evidence
      of specificity, especially for runners preparing for longer events. A potentially
      beneficial effect of specificity was evident in a significant (p < 0.01)
      correlation between performance and seasonal mean weekly duration of moderate
      continuous running for runners specialising in longer distances (r = 0.29). The
      only other significant correlates of performance were seasonal mean relative
      training paces of moderate (r = -0.18) and hard (r = -0.42) continuous running,
      which exemplified detrimental effects of specificity for most runners. Thus, the
      training of better runners is not characterised strongly by greater specificity.

PMID- 8739575
TI  - Effects of exhaustive endurance exercise and its one-week daily repetition on
      neutrophil count and functional status in untrained men.
AB  - Whereas endurance exercise is known to induce marked neutrophilia, it remains to
      be fully understood as to whether the cell functions are altered as well as
      whether the adaptability of the responses to training occurs. To address both of
      these issues, we undertook the present longitudinal investigation in ten healthy
      untrained men (20-24 years, VO2max 39.1 +/- 4.2 ml/kg/min). The exercise protocol
      was 7 consecutive sessions of the same workload performed each day for 1.5 h at
      an intensity of 70% of VO2max. Peripheral blood samples were obtained before,
      immediately after, and 1 h after exercise on Days 1, 4, and 7, and served for
      determination of total and differential leukocyte counts, chemotaxis and
      chemiluminescence of neutrophils. Acute endurance exercise caused marked
      peripheral neutrophilia with significant increase in both absolute number and
      relative proportion of band neutrophils (p < 0.01, respectively), indicating
      partial recruitment of bone marrow neutrophils. While chemotaxis remained
      unaltered following exercise, reactive oxygen species generation of neutrophils,
      measured by luminol-dependent chemiluminescence upon stimulation with opsonized
      zymosan, was not only significantly enhanced following exercise (p < 0.01), but
      also associated with the proportional increase in band neutrophils (r = 0.727, p
      < 0.05), suggesting that neutrophils mobilized from the bone marrow following
      endurance exercise may possess higher responsiveness. On the other hand, the
      magnitude of the exercise-induced changes was reduced gradually by daily repeated
      exposure to endurance exercise, but none of the trends were significant except
      the decline in resting segmented neutrophil counts (p < 0.05) at least during a 1
      wk period of repeated exercise sessions.

PMID- 8739576
TI  - Effects of training and taper on blood leucocyte populations in competitive
      swimmers: relationships with cortisol and performance.
AB  - The effects of 12 weeks of training and 4 weeks of taper on blood leucocyte
      populations and cortisol were investigated in 8 well-trained competition
      swimmers. Blood samples were taken at rest in the mid-season (week 10), before
      taper (week 22) and after taper (week 26). Swimmers improving by more than 2%
      with taper (N = 4), efficient (GE), were compared with swimmers improving by less
      than 2% (N = 4), less efficient (GLE). No significant changes were observed in
      leucocyte subpopulations or cortisol during training. The percentage of
      neutrophils decreased during taper (p < 0.05). Basophils and the percentage of
      granulocytes tended to decrease, while lymphocytes tended to increase. The
      increment in lymphocytes was positively related with the reduction in training
      volume during taper (r = 0.86, p < 0.05). Cortisol levels did not change with
      taper and were not related with leucocyte status and kinetics. GE swimmers had
      higher pre- and post-taper eosinophil counts than GLE swimmers (p < 0.05).
      Lymphocyte counts in GE tended to be higher, too. Cortisol decreased with taper
      in GE, while it increased in GLE. In conclusion, taper appeared to have an
      influence on leucocyte populations, which did not seem to be related with blood
      cortisol.

PMID- 8739577
TI  - The diagnostic validity of magnetic resonance imaging in acute knee injuries with
      hemarthrosis. A single-blinded evaluation in 69 patients using high-field MRI
      before arthroscopy.
AB  - Sixty-nine patients with traumatic knee hemarthrosis were evaluated an average of
      3 days after trauma by high field (1.5T) magnetic resonance imaging (MRI) using
      sagittal T1, T2-weighted and coronal 3D-gradient echo images. All knees were
      arthroscopically examined shortly afterwards. The diagnostic validity of MRI for
      intraarticular pathology was determined using arthroscopy as golden standard. All
      patients had pathological findings on arthroscopy. The injuries were sports
      related in 77% of the cases. MRI was highly sensitive (86%) and specific (92%)
      for diagnosis of anterior cruciate ligament tears. Diagnosis of medial meniscal
      tears showed a 74% sensitivity and 66% specificity. MRI detected lateral meniscal
      tears in 50% with an 84% specificity. As such, MRI missed 10 significant meniscus
      ruptures requiring surgical treatment. The sensitivity for partial or total
      medial collateral ligament tears was 56%, the specificity 93%. Rupture of the
      medial retinaculum in cases with patellar dislocation or significant damage of
      articular cartilage were only detected by MRI in a few cases (27% and 20%
      sensitivity, respectively). MRIs low diagnostic validity for intraarticular
      pathology with hemarthrosis may be attributed to the shifting paramagnetic
      properties of the blood remains and catabolic processes in meniscal and chondral
      tissues during the hemoglobin degradation process. Accordingly, MRI, with the
      technique used, could neither replace arthroscopy in the diagnosis and screening
      of acute knee injuries, nor select patients with need for immediate arthroscopic
      meniscal surgery.

PMID- 8739578
TI  - Isokinetic muscle performance after anterior cruciate ligament surgery. Long-term
      results and outcome predicting factors after primary surgery and late-phase
      reconstruction.
AB  - The purpose of this study was to evaluate the long-term isokinetic muscle
      performance after ACL surgery and to analyze by a multiple stepwise regression
      which factors (if any) predict the overall outcome. The study subjects were 119
      patients who had a complete rupture of the ACL and had been treated surgically at
      the Tampere University Hospital between 1981 and 1990. They were divided into the
      acute group (N = 62) and into the chronic group (N = 57) according to the time
      delay between the injury and the ACL surgery. The isokinetic strength
      measurements of the quadriceps and hamstring muscles were performed on average 4
      years after the operation using Cybex II and Cybex 6000 dynamometers (Lumex Inc.,
      Ronkokoma, NY, USA). The peak torques were determined at speeds of 60 and 180
      degrees/s and the peak work at speed of 180 degrees/s. The measurements revealed
      that after the ACL surgery there was still a considerable thigh muscle strength
      deficit especially in extension of the injured extremity, the average extension
      strength deficit ranging from 9 to 20%. The extension strength deficit was
      significantly more prominent in the chronic (18-20%) than in the acute group (9
      15%). The extension strength deficit was significantly greater ar the slower (15
      20%) than higher (9-18%) speed of the isokinetic movement. In both the acute and
      chronic groups, a multiple stepwise regression analysis indicated that
      patellofemoral pain and flexion deficit of the knee were the factors that most
      frequently and significantly associated with the strength deficits. At the higher
      speed of the isokinetic movement, these two factors accounted 20% and 21% for the
      variation seen in the quadriceps strength deficit of the acute group and the
      chronic group. No correlation could be found between age, sex, height, weight,
      body mass index, length of the follow-up time, injury type, athletic activity
      level, immobilization method, knee stability, and the isokinetic muscular
      performance.

PMID- 8739579
TI  - Injuries in male soccer players: team risk analysis.
AB  - Selection may be responsible for different characteristics of subgroups (teams)
      of soccer players resulting in different risks of injury and different injury
      patterns. In the present study injury rates of teams were analysed with respect
      to the factors age and level of play. In two Dutch non-professional soccer clubs
      477 male players, active in teams of different age groups and at different levels
      of play, were prospectively followed during the second half of the 1986/1987
      competitive season. Teams in the 17/18 years age group showed the highest
      incidence of injury per 1000 players hours in games. At a high level of play
      teams have a significantly (p < 0.01) higher risk of injury than teams at a low
      level of play. This difference is noticed within every age group with exception
      of the 15/16 years age group. At a high level of play teams of senior players
      have significantly (p < 0.005) more prevalent injuries than teams of junior
      players. Senior players, active at a high level of play, have significantly (p <
      0.05) more overuse injuries than senior players of a low level of play. At a high
      level of play significantly (p < 0.05) more upper leg injuries are reported. In
      the total population of soccer players relatively more sprains are located in the
      ankle joint and relatively more strains are located on the upper leg. It is
      concluded that prevention of soccer injuries primarily should be aimed at teams
      and their environment and not at the individual soccer player.

PMID- 8739580
TI  - Effect of treatment with nasal IgA on the incidence of infectious disease in
      world-class canoeists.
AB  - Earlier studies of endurance athletes have shown decreased levels of secretory
      IgA and an increased frequency of upper respiratory tract (URT) infections after
      periods of hard training. In this study, 14 world-class canoeists were studied
      during very hard physical training, after lower-intensity training combined with
      17 days of treatment with nasal IgA, and during low intensity training off
      season. The ELISA method was used to determine IgA in nasopharyngeal (nph)
      secretions and saliva (s). The results demonstrated unchanged nph secretions
      before, during and after IgA treatment (IgAbulin, Immuno AG, Vienna, Austria).
      Saliva Ig-A increased significantly from a median value of 147 micrograms/ml
      (range 37-634) to 410 micrograms/ml (range 82-974) (p < 0.05) during treatment.
      Thereafter, s-IgA decreased to 244 micrograms/ml (range 85-689) off-season. A
      control group of untrained students showed similar nph IgA to that of the elite
      canoeists. The athletes receiving nasal IgA showed no signs of URT and were
      considered healthy during 14.5 days out of 17 days of treatment as compared to
      12.3 healthy days out of 17 days in the control group. In summary there was no
      significant decrease in IgA in untreated elite canoeists as compared to untrained
      controls. Nasal IgA treatment increased the IgA level in saliva only, but no
      significant decrease in URT symptoms was seen during the IgA treatment period.

PMID- 8739581
TI  - "Sex passport" obligation for female athletes. Consideration and criticisms on
      364 subjects.
AB  - In Ancient Greece determination of sex was made by direct observation of the all
      male athletes participating in the Olympic Games. In 1966 the International
      Olympic Committee (I.O.C.) established that female athletes must submit to a
      complete physical examination before each international competition. In 1968 they
      further established that each female participant be granted a "Sex Passport"
      based upon the findings of a medical and gynaecological examination as well as
      chromosomal sex determination. The authors, whose department has been responsible
      for granting Sex Passports for more than 20 years, examined 364 female athletes
      aged 16 to 29 years using I.O.C. criteria. They found three chromatic-negative
      cases (0.8%). The present work indicates several scientific shortcomings of the
      current I.O.C. examination criteria, illustrates three chromatin-negative cases,
      their consequences and proposed a return to original criteria for examination
      except in doubtful cases.

PMID- 8739582
TI  - Prenatal spinal evaluation and functional outcome of patients born with
      myelomeningocele: information for improved prenatal counselling and outcome
      prediction.
AB  - OBJECTIVE: Prenatal ultrasonography can localize the level of the spinal cord
      malformation, allowing prediction of the potential postnatal neurological deficit
      and functional prognosis. METHODS: This study has two evaluations: (a) a
      retrospective prenatal review of 26 fetuses with spinal dysraphism (1987-1991),
      and (b) a follow-up descriptive study of patients (1971-1981) who underwent
      closure of the spinal lesion and ventricular shunting in the neonatal period.
      RESULTS: Prenatal ultrasound evaluation enabled the accurate definition of the
      last intact vertebral level which allows separation of fetuses into three
      functional groups (last intact level L2, L3-4, L5-sacral). Patterns of
      ambulation, urinary and bowel continence, and school performance vary according
      to level of spinal lesion and the neurological deficit. The need for ventricular
      shunts, the incidence of other spinal malformations and surgical interventions
      did not vary with the level of the spinal lesion. CONCLUSIONS: The functional
      outcome for patients with myelomeningocele is variable; however, distinct
      patterns emerge based on the level of spinal dysraphism and the resultant
      neurological deficit. By relating the level of the fetal spinal lesion to outcome
      data, more precise functional prognoses can be given to families.

PMID- 8739583
TI  - Diagnostic fetal blood sampling-technique related losses.
AB  - BACKGROUND: The applications of cordocentesis are limited by its safety.
      Cordocentesis is performed either freehand or with the aid of a fixed needle
      guide. Recent reports suggest a loss rate of 1-7% using the freehand technique.
      The potential influence of technique on the perinatal loss rate has not been
      examined. STUDY DESIGN: The procedure-related loss rates of two fetal diagnosis
      and treatment units, one in the United States (10 operators) and one in Japan (15
      operators), who perform diagnostic cordocentesis with the aid of a fixed needle
      guide is calculated from a prospectively maintained database and compared to the
      published experience of large centers who use a freehand technique. RESULTS: A
      total of 1,260 diagnostic cordocenteses were performed. The mean gestation at
      sampling was 29.1 +/- 5 weeks. The umbilical vein was punctured in 90%. There
      were 12 procedure-related losses yielding an overall perinatal loss rate of 0.9%.
      There was no relationship between the risk of a loss and the number of prior
      procedures the operator had performed. Losses were more often associated with
      puncture of the umbilical artery (41.7 vs. 9.2%, p = 0.002). Eleven of 12 losses
      were associated with a postprocedure bradycardia. Eight fetuses who died had
      either a trisomy or triploidy, 1 had renal agenesis, 2 had severe early-onset
      growth restriction and 1 had rhesus disease. For all diagnoses other than a
      chromosome abnormality and severe fetal growth restriction, the procedure-related
      loss rate from diagnostic cordocentesis was 0.2% (2/1,021). CONCLUSION: This
      study suggests that technique is a variable in the loss rate for cordocentesis.

PMID- 8739584
TI  - Amniotic fluid pressure in twin-to-twin transfusion syndrome: an objective
      prognostic factor.
AB  - Severe twin-to-twin transfusion syndrome presenting before 28 weeks' gestation is
      associated with a high neonatal mortality and morbidity due to polyhydramnios
      related very premature delivery or intrauterine death of one or both twins.
      Management options include serial amniodrainages or laser coagulation of the
      intertwin placental anastomoses; however, early antenatal prognostic factors are
      lacking. Serial amniocenteses were performed in 9 pregnancies with twin-to-twin
      transfusion syndrome presenting with second-trimester polyhydramnios, and serial
      measurements of amniotic fluid pressure were made. Although in 8 cases the pre
      drainage pressure was above the 95th centile of the normal range for singleton
      pregnancies, the pressures were lower in the pregnancies resulting in two
      livebirths than in the cases where one or both babies died. This study suggests
      that patients presenting with intraamniotic pressure > 17 mm Hg cannot be safely
      managed by serial amniodrainages.

PMID- 8739585
TI  - Outcome of urological abnormalities prenatally diagnosed by ultrasound.
AB  - In order to evaluate the efficiency of antenatal diagnosis and postnatal
      management of urinary malformations, we reviewed 142 cases from October 1988 to
      December 1992 with abnormalities detected by routine ultrasound. A routine
      karyotype analysis showed 7 fetuses with chromosomal defects. Nine cases with
      isolated bilateral urinary tract dilatation underwent pelvic fetal urine sampling
      in order to assess antenatal renal function. The 142 cases comprised 107 children
      born alive (group I) and 35 intrauterine fetal deaths (group II). In group I, 79
      kidneys had a transient pyelectasis, and 11 kidneys had a hydronephrosis which
      disappeared at postnatal examination. Among 103 pyelectasis cases detected during
      the second trimester of pregnancy, 22 kidneys were pathological after birth
      (positive predictive value (PPV) = 21.4%) with 17 ureteropelvic junction
      obstructions. The PPV was 66% when ultrasound showed hydronephrosis at the end of
      pregnancy. In that group, 15 cases had vesicoureteric reflux, with 5 cases where
      the homolateral upper urinary tract was morphologically normal in utero. Group II
      comprised 27 fetuses with multiple defects in other systems, and 8 cases with
      urological defects only 7 of which had urethral anomalies. This study confirmed
      the benefit of antenatal diagnosis for uropathies, and the advantage of prenatal
      consultation between pediatric surgeon and parents in order to explain what
      anomalies are involved and to program postnatal follow-up.

PMID- 8739586
TI  - Antenatal diagnosis of upper urinary tract dilation by ultrasonography.
AB  - The criteria for the detection of fetal pyelectasis are still controversial.
      Prenatal and postnatal data from 2,170 consecutive pregnant women who underwent
      at least one antenatal ultrasound scan were prospectively studied. Fetal
      pyelectasis was defined on the basis of a mean renal pelvis dimension > 5 or 10
      mm before or after 28 weeks of gestation, respectively. Pyelectasis was detected
      in 95 (4.4%) fetuses. Eighty-nine among them were explored after birth. In 13
      (13.7%) cases, an obstructive urinary tract abnormality, a severe vesicoureteral
      reflux, or a megaureter were diagnosed postnatally. In 29 (30.5%) cases,
      pyelectasis was confirmed postnatally, while complementary investigations ruled
      out an obstruction of the urinary tract. The incidence of urinary tract
      malformations was thus 0.60%, while the positive predictive value was 13.7%. We
      recommend to use a value not < 10 mm of the renal pelvis mean dimension beyond 28
      weeks of gestation as a threshold for detection of fetal upper urinary tract
      obstruction, in the absence of ureteric and/or bladder dilation. Any value
      between 5 and 10 mm measured during the 2nd trimester of gestation should be
      confirmed by a second ultrasound examination performed during the 3rd trimester,
      before being considered pathological.

PMID- 8739587
TI  - First-trimester translucency: aneuploidy, sonographic findings, and maternal age.
AB  - The positive predictive value of 1st-trimester nuchal translucency for the
      diagnosis of fetal aneuploidy is reported to range from 19 to 72% in
      retrospective series and from 2.8 to 4.8% in prospective studies. In order to
      analyze the biases accounting for such discrepancies, we retrospectively analyzed
      a consecutive series of 66 cases of translucency and studied the rate of
      aneuploidy as a function of sonographic findings and maternal age. The aneuploidy
      rate was significantly higher in the 23 cases in whom translucency involved the
      fetal trunk (65%) than in the 43 cases in whom translucency was confined to the
      nuchal area (16%). This rate was not significantly higher in septated
      translucencies. These trends persisted after adjustment for maternal age, but the
      rate of chromosomal anomalies was twice lower in younger mothers. Among the 46
      cases in whom the maternal age was < 35 years, 10% of the 30 fetuses with
      localized nuchal translucency had an abnormal karyotype. In contrast, the rate of
      aneuploidy was 85% among the 7 cases with diffuse translucency for whom the
      maternal age was 35 years or above. These findings confirm that both maternal age
      and size of the translucency should be taken into account to evaluate the risks
      of aneuploidy.

PMID- 8739588
TI  - Role of prenatal diagnosis in the treatment of congenital obstructive megaureter
      in a solitary kidney.
AB  - Congenital megaureter in a solitary kidney (CMSK) is a life-threatening disease.
      From January 1988 to December 1993, we treated 9 patients for CMSK (2 cases with
      unilateral renal dysplasia and 7 with unilateral renal agenesis). In 7 cases, the
      malformation was detected by prenatal ultrasonography and urological counseling.
      The ages at first postnatal observation ranged from 24 h to 5 years (mean = 8
      months). The postnatal urological workup included: serum renal function
      screening, urinary system ultrasonography, a micturition cystogram, intravenous
      pyelography and a nuclear renal scan. The therapy of choice was decided on the
      basis of renal function. One emergency divertive procedure was performed after
      birth, in 3 cases of renal failure in the first 2 weeks of life. The remaining
      cases were operated electively at an average age of 20 months. In 2 cases that
      underwent delayed surgical elective correction and in 1 of the 3 cases that
      underwent an emergency diversion, some degree of renal failure still persists. In
      our opinion, prenatal diagnosis, accurate postnatal urological workup and strict
      postoperative follow-up are fundamental to avoid the devastating consequences of
      CMSK on the affected child.

PMID- 8739589
TI  - Antenatal invasive and noninvasive management of alloimmune thrombocytopenia.
AB  - The outcome analysis of 10 pregnancies at risk for neonatal alloimmune
      thrombocytopenia (NAIT) is presented. An experimental protocol of cordocentesis
      and maternal administration of intravenous immunoglobulin (IVIG) is compared to a
      control group of older untreated affected siblings. The outcome in pregnancies
      treated with IVIG shows improved fetal platelet count in 70% and no
      intraventricular hemorrhage. We conclude that maternal administration of IVIG
      appears to improve clinical outcome in fetuses at risk for NAIT.

PMID- 8739590
TI  - Decompression of fetal axillary lymphangioma to prevent dystocia.
AB  - BACKGROUND: Lymphangiomas are commonly diagnosed by prenatal ultrasound. These
      anomalies are most often cervical, but occasionally present in the axilla, thorax
      and abdomen. We present a case in which intrauterine drainage was followed by an
      uneventful vaginal delivery. CASE: A 30-year-old G4P3 female was referred to our
      ultrasound unit at 36 weeks of gestation for evaluation of a large cystic chest
      wall mass. Ultrasound demonstrated a large septated mass along the left chest
      wall up to the apex of the axilla of the fetus. The left arm was held in 90
      degrees abduction due to the mass. Because of concern about shoulder dystocia at
      delivery the cystic mass was aspirated under ultrasound guidance and the patient
      underwent an uneventful induction of labor. CONCLUSIONS: Intrauterine
      decompression of large axillary lymphangiomas may obviate concern about a
      shoulder dystocia and avoid the need for cesarean sections.

PMID- 8739591
TI  - A case of varix dilatation of the umbilical vein and review of the literature.
AB  - Umbilical cord cysts diagnosed antenatally present a challenge to the clinician
      as they may be associated with adverse perinatal outcomes including abnormal
      karyotypes and stillbirths. We present a case of an umbilical cord cyst diagnosed
      by routine ultrasound at 30 weeks of gestation. Findings on sonography included
      unidirectional movement of echogenic particles suggesting a large varix of the
      umbilical vein. The patient delivered vaginally at 39 weeks and histopathology
      confirmed the diagnosis.

PMID- 8739593
TI  - Mechanisms for the anti-hepatitis B virus activity and mitochondrial toxicity of
      fialuridine (FIAU).
AB  - Fialuridine (FIAU) is a thymidine nucleoside analog with activity against various
      herpesviruses and hepatitis B virus (HBV) in vitro and in vivo. In a clinical
      evaluation for its use as a treatment for chronic HBV infection, long term (HBV)
      in vitro and in vivo. In a clinical evaluation for its term oral administration
      of FIAU resulted in severe multi-organ toxicity characterized by a delayed onset
      and refractory lactic acidosis. These clinical manifestations led to the
      hypothesis that the toxicity of FIAU was mediated through mitochondrial
      dysfunction, possibly as a result of the inhibition of mitochondrial DNA
      polymerase gamma and/or incorporation of FIAU into mitochondrial DNA. In addition
      to describing the anti-HBV activity of FIAU, this review discusses results from
      in vitro experiments carried out by various laboratories in an effort to evaluate
      and understand more fully the mitochondrial toxicity of FIAU.

PMID- 8739592
TI  - Prenatal diagnosis of thrombocytopenia-absent radius syndrome.
AB  - Thrombocytopenia-absent radius (TAR) syndrome is an autosomal-recessive disorder
      characterized by a thrombocytopenia and a bilateral radial aplasia with normal
      thumbs. Only TAR syndrome, out of diseases which may present with radial aplasia,
      typically has normal thumbs. The prenatal diagnosis is rarely made. We report two
      observations of TAR syndrome diagnosed in utero in the sibling. The malposition
      of fetal hands detectable as soon as 11 weeks of gestation requires careful
      search for longitudinal limb defect of the forearm, especially radial ray defect.
      The radial aplasia is associated with numerous causes (chromosomal, teratogenic,
      genetic, multifactorial). The determination of fetal hematologic values revealing
      a thrombocytopenia allows the prenatal diagnosis of the index case of TAR
      syndrome.

PMID- 8739594
TI  - Famciclovir: review of clinical efficacy and safety.
AB  - Famciclovir is the well-absorbed oral form of penciclovir, an antiviral agent
      with potent activity against varicella-zoster virus (VZV) and herpes simplex
      virus (HSV-1) and 2 (HSV-2). After oral administration, famciclovir is rapidly
      converted to penciclovir with a bioavailability of 77%. penciclovir is
      efficiently phosphorylated to the active metabolite, penciclovir-triphosphate,
      and has a prolonged intracellular half-life of approximately 9-10 h in VZV
      infected cells, and 10 and 20 h in cells infected with HSV-1 and HSV-2,
      respectively. Two multicenter clinical trials have shown that famciclovir given
      during the acute zoster phase accelerated healing of cutaneous lesions. More
      importantly, in a placebo-controlled study, famciclovir reduced the duration of
      postherpetic neuralgia (PHN), particularly in elderly patients. Famciclovir has
      also been proven effective in treating recurrent genital herpes, as demonstrated
      by a reduction in times to cessation of viral shedding, complete healing, and
      loss of all symptoms. One study showed that suppressive therapy with famciclovir
      was effective in reducing genital herpes episodes in patients with frequent
      recurrences. A promising new area of investigation for famciclovir is controlling
      virus replication in patients with chronic hepatitis B virus (HBV) or HBV
      reinfections after liver transplant. Results from a double-blind, placebo
      controlled, pilot study and several case reports have shown that famciclovir,
      alone or in combination with other agents, decreased HBV-DNA levels and was
      tolerated with long-term treatment. Available clinical data indicate that
      famciclovir is an effective agent for treating herpes and holds significant
      promise for the treatment of chronic HBV infection HBV reinfection after liver
      transplantation.

PMID- 8739595
TI  - Pharmacokinetics, safety and bioavailability of HPMPC (cidofovir) in human
      immunodeficiency virus-infected subjects.
AB  - We conducted a single-center, double-blind, placebo-controlled phase I study in
      HIV-positive subjects to ascertain the safety, tolerance, bioavailability,
      pharmacokinetics, and maximum tolerated dose of HPMPC (cidofovir). Five subjects
      were randomized to receive drug and two to receive placebo at each of three
      dosage tier (1, 3, and 10 mg/kg) with a 2-week washout period doses. Subjects at
      1 and 3 mg/kg received single doses of HPMPC by subcutaneous (s.c.) intravenous
      (i.v.), and oral (p.o.) routes, while subjects at 10 mg/kg received only i.v. and
      p.o. doses. For subjects already taking zidovudine, zidovudine AUC values are
      determined before and then with HPMPC administration for each route. The AUC
      values of HPMPC were dose-proportional. Subcutaneous bioavailability was
      essentially equivalent to that of the intravenous route, but the development of
      transient local fibrosis ad the volumes needed for subcutaneous dosing precluded
      higher subcutaneous dosing than 3 mg/kg. Oral bioavailability was poor, estimated
      to be less than 5%. Drug elimination was predominantly renal. Nephrotoxicity in
      one subject was the only serious adverse event observed. This subject had a
      significant lag period prior to oral absorption and also had the highest AUC
      values for both HPMPC and zidovudine. We found no consistent effect on zidovudine
      AUC concomitant HPMPC.

PMID- 8739596
TI  - Inhibition of human immunodeficiency virus type 1 infectivity by a new amine
      bellenamine.
AB  - Bellenamine, (R)-3,6-diamino-N-(aminomethyl)hexanamide (molecular weight 174),
      produced by Streptomyces nashvillensis, which has been reported to have weak
      antibacterial activity and to slightly enhance the immune response, showed potent
      activity against human immunodeficiency virus type 1 (HIV-1). Its mode of action
      was investigated. Bellenamine inhibited de novo infection of human T cells with
      HIV-1, at a 50% effective concentration (EC50) of 0.62 micrograms/ml (3.6
      microM). Its 50% cytotoxic concentration (CC50) was over 2000 micrograms/ml (11.5
      mM) and thus its cytotoxicity was quite low. When HIV-1-infected cells were
      treated with bellenamine or glycosylation inhibitors, they produced virus with
      reduced infectivity, and thus bellenamine inhibited the secondary spread of HIV-1
      in vitro similarly to glycosylation inhibitors. However, bellenamine did not
      change the apparent molecular weights of env or gag proteins, unlike
      glycosylation inhibitors. Bellenamine showed no significant activity against
      virus adsorption, reverse transcriptase, viral protease or the glycosylation
      process. The antiviral mechanism of bellenamine remains to be examined further.

PMID- 8739597
TI  - Effects of SKF 108922, an HIV-1 protease inhibitor, on retrovirus replication in
      mice.
AB  - Rationally designed synthetic inhibitors of retroviral proteases inhibit the
      processing of viral polypeptides in cultures of human T lymphocytes infected with
      human immunodeficiency virus type 1 (HIV-1) and therefore suppress the
      infectivity of HIV-1 in vitro. We have previously reported the antiviral activity
      in vitro of HIV-1 protease inhibitors against the C-type retrovirus Rauscher
      murine leukemia virus (RMuLV) and the lentivirus simian immunodeficiency virus
      (SIV). The same compounds which blocked the infectivity of HIV-1 also inhibited
      the infectivity of RMuLV and SIV in vitro. This report extends these findings by
      testing the antiviral activity of HIV-1 protease inhibitors in vivo in the RMuLV
      model. RMuLV-infected mice were treated twice a day (bid) with either an active
      (SKF 108922) or inactive (SKF 109273) compound for fourteen days by the
      intraperitoneal (i.p.) route. Compared with excipient control, SKF 108922,
      formulated with hydroxypropyl-beta-cyclodextrin (HPB), reduced virus-induced
      splenomegaly, viremia, and serum reverse transcriptase (RT) levels, while SKF
      109273 was inactive. The HPB vehicle by itself enhanced replication of RMuLV. The
      effects of changing the formulation and the route of administration were
      examined. SKF 108922, formulated in HPB, had similar antiviral activity when
      administered by the i.p. or subcutaneous (SC) routes. However, SKF 108922
      administered as a colloidal suspension in cholesterol sulfate (CS) had no
      detectable antiviral effect. Measurements of the circulating levels of the
      protease inhibitor in plasma explained this result. Plasma concentrations of SKF
      108922 exceeded 1000 nM within 10 min after SC administration of the compound
      solubilized in HPB, but SKF 108922 was not detected in plasma after SC
      administration of the same dose formulated with CS. Information on optimal
      conditions for administering these agents should prove useful in guiding their
      clinical application Therefore, RMuLV should provide a good model for the
      preclinical evaluation and development of this class of agents for the treatment
      of HIV.

PMID- 8739598
TI  - Effect of combined alpha IFN and prostaglandin A1 treatment on vesicular
      stomatitis virus replication and heat shock protein synthesis in epithelial
      cells.
AB  - The antiviral activity of prostaglandin A (PGA) and interferons (IFNs) has been
      widely described. In the present report, we investigated the effect of combined
      alpha IFN and PGA1 treatment on vesicular stomatitis virus (VSV) replication and
      on heat shock protein (HSP) induction in monkey epithelia cells. In uninfected
      cells, PGA1 caused a dose-dependent induction of HSP70, HSP90 and HSP110, while
      alpha IFN did not affect HSP synthesis. Alpha-IFN suppressed VSV replication dose
      dependently, even when cells were treated after virus infection. VSV protein
      synthesis was not affected by alpha IFN, indicating a block at the level of virus
      assembly or maturation. PGA1 caused a dose-dependent inhibition of VSV
      replication, and suppressed VSV protein synthesis at concentrations which induced
      the synthesis of high levels of HSP70. The combined treatment with low doses of
      alpha IFN or PGA1, which only moderately inhibited VSV replication when
      administered separately, was found to suppress VSV production by more than 95%,
      and resulted in a 3-fold increase of HSP70 synthesis as compared to PGA1 alone.
      These results demonstrate a co-operative effect of PGA1 and alpha IFN against VSV
      infection and suggest that alpha IFN can potentiate the cellular response to HSP
      induction in virus-infected cells.

PMID- 8739599
TI  - Effect of liposome-encapsulation on immunomodulating and antiviral activities of
      interferon-gamma 1.
AB  - The effect of liposome-encapsulation on the immunomodulating and antiviral
      activities of interferon-gamma (IFN-gamma) was evaluated in this study. The
      immunomodulating activity was measured by increases in phagocytic activity and in
      nitric oxide production by peritoneal macrophages from mice treated with both
      free and LIP-IFN-gamma (4000 U/mouse, intraperitoneal injection). Resident
      peritoneal macrophages harvested from mice treated with free unencapsulated IFN
      gamma or muramyl dipeptide showed significant increases in macrophage yield, and
      enhanced ability to phagocytize zymosan particles. In mice treated with liposome
      encapsulated IFN-gamma (LIP-IFN-gamma), both macrophage yield and phagocytic
      activity further increased by 2-fold over unencapsulated IFN-Y. In addition, the
      activation of peritoneal macrophages with LIP-IFN-gamma showed enhanced
      production of NO when the cells were cultured ex vivo. Using a murine respiratory
      influenza infection model, intranasally administered LIP-IFN-gamma conferred
      protection to 70% in mice challenged intranasally with 10 LD50 doses of influenza
      A/PR/8 virus compared with a 20% survival rate using free IFN-gamma. Together
      these results suggest that liposome-encapsulation increases the immunomodulating
      and antiviral activities of IFN-gamma. Liposome-encapsulation of IFN-gamma may
      provide additional therapeutic advantages by reducing IFN-gamma toxicity while
      prolonging its body retention.

PMID- 8739600
TI  - The bicyclams, a new class of potent human immunodeficiency virus inhibitors,
      block viral entry after binding.
AB  - The bicyclams represent a new class of highly potent and selective HIV
      inhibitors. Time-of-addition experiments have previously shown that these
      compounds interfere with an early event in the viral replicative cycle.
      Additional experiments have now been carried out in order to investigate in more
      detail the mechanism of action of these promising compounds. As described in this
      paper, PCR experiments revealed that no viral DNA was formed following viral
      infection, thus confining the target(s) of action of the bicyclams to an early
      stage of HIV infection. An assay, using pseudotype virions containing the
      envelope of HIV-1 and the genome of a plaque-forming virus (Cocal Virus), pointed
      to viral entry as the main target of the bicyclams. HIV-1 strains resistant to
      two prototype bicyclams, JM2763 and SID791 (JM3100), were raised. Results
      obtained with SID791 with respect to syncytium formation induced by SID791
      sensitive and -resistant HIV-1 strains and the cross-resistance observed for
      dextran sulfate, suggest inhibition of binding and/or fusion as a plausible
      target of SID791. Additional experiments enabled us to exclude SID791 and JM2763
      as binding inhibitors and to conclude that bicyclams block the entry of cell
      bound virus. Furthermore, a monoclonal antibody recognising the V3 loop of wild
      type gp120 did not bind to this region in the two bicyclam-resistant strains. Our
      results point to gp120 as a possible target for the HIV-inhibitory effects of the
      bicyclams.

PMID- 8739601
TI  - Lactoferrin inhibits herpes simplex virus type 1 adsorption to Vero cells.
AB  - This paper describes the ability of human and bovine lactoferrins (HLf; BLf),
      iron-binding proteins belonging to the non-immune defense system, to interfere
      with herpes simplex virus type 1 (HSV-1) infection. Since lactoferrins are known
      to bind to heparan sulphate proteoglycans and to low density lipoprotein
      receptor, which in turn act as binding sites for the initial interaction of HSV-1
      with host cells, we tested the effect of these proteins on HSV-1 multiplication
      in Vero cells. Both HLf and BLf are found to be potent inhibitors of HSV-1
      infection, the concentrations required to inhibit the vital cytopathic effect in
      Vero cells by 50% being 1.41 microM and 0.12 microM, respectively. HLf and BLf
      exerted their activity through the inhibition of adsorption of virions to the
      cells independently of their iron withholding property showing similar activity
      in the apo- and iron-saturated form. The binding of [35S]methionine-labelled HSV
      1 particles to Vero cells was strongly inhibited when BLf was added during the
      attachment step. BLf interacts with both Vero cell surfaces and HSV-1 particles,
      suggesting that the hindrance of cellular receptors and/or of viral attachment
      proteins may be involved in its antiviral mechanism.

PMID- 8739602
TI  - Efficacy of BMS-180194 against experimental cytomegalovirus infections in
      immunocompromised mice.
AB  - A new antiviral nucleoside, BMS-180194 [1R-(1 alpha, 2 beta, 3 alpha)]- 2-amino
      9[2,3-bis(hydroxymethyl)cyclobutyl]-1,9dihydro-6H-purin-6- one, is a broad
      spectrum antiviral agent. The antiviral effectiveness of BMS-180194 against
      murine cytomegalovirus (MCMV) infection in immunocompromised C57BL/6 mice was
      investigated and was compared to that of ganciclovir (GCV). LP-BM5 murine
      retrovirus complex-induced immunocompromised C57BL/6 mice were challenged with
      MCMV then treated intraperitoneally or per os with various doses of BMS-180194
      ranging from 30 to 3 mg/kg/day. When administered intraperitoneally, BMS-180194
      was effective against MCMV-mediated mortality in a dose-dependent manner
      demonstrating a 50% protective dose (PD50) of 3.12 mg/kg/day which was comparable
      to that of GCV. There was a marked reduction in organ MCMV titers in BMS-180194
      treated animals (10-10,000- fold lower than the placebo controls). Similar
      findings were observed when the compound was administered orally. Interestingly,
      oral BMS-180194 demonstrated a similar antiviral efficacy as that obtained by the
      parental route of administration suggesting a high oral bioavailability of the
      compound. Oral ganciclovir treatment, however, required more than a 4-fold higher
      amount of GCV to confer the same degree of protection obtained by a parenteral
      route of administration. Oral BMS-180194 was also effective in reducing the organ
      MCMV titer in genetically severe combined immunodeficient (SCID) mice. The
      parenteral or oral antiviral efficacy of BMS-180194 was comparable to that of
      parenteral ganciclovir against MCMV infection in the present study. Doses of BMS
      180194 employed in the present study showed no toxicity to mice. These results
      suggest that BMS-180194 may be of value as an oral antiviral agent for treatment
      of opportunistic CMV infections in immunocompromised individuals.

PMID- 8739603
TI  - Antisense oligodeoxynucleotides against the BZLF1 transcript inhibit induction of
      productive Epstein-Barr virus replication.
AB  - Expression of the Epstein-Barr virus (EBV) BZLF1 gene product, ZEBRA, in latently
      infected cells is sufficient to induce the viral lytic cycle. The use of
      oligodeoxynucleotides complementary to the BZLF1 transcript was studied to
      inhibit this induction of productive viral replication. For this purpose, we
      employed oligodeoxynucleotides complementary to the translation initiation codons
      and their flanking sequences. Incubation of Akata cells with the 25-mer
      phosphodiester (PO)- or phosphorothioate (PS)-antisense oligodeoxynucleotides for
      3 h before stimulation with anti-immunoglobulin G antibodies (anti-IgG) partially
      inhibited the anti-IgG-mediated induction of ZEBRA synthesis. Both the PO- and PS
      antisense oligodeoxynucleotide treatments also suppressed the productive EBV
      replication (as measured by linear DNA production) in a dose-dependent manner,
      with much greater efficiency than did PO and PS-oligodeoxynucleotides with sense,
      reverse or random sequences of the same length. Another 20-mer antisense
      oligodeoxynucleotide complementary to sequences downstream of the translation
      initiation codons showed a similar inhibitory effect on EBV replication. However,
      the inhibition was considerably lower when the cells were treated with
      oligodeoxynucleotides complementary to sequences upstream of the start codons.
      These results indicate that BZLF1 antisense oligodeoxynucleotides inhibit the
      viral activation in a sequence-specific fashion. In the virus-producer cell line
      P3HR-1, the same PS-antisense oligodeoxynucleotides also partially suppressed the
      spontaneous viral replication after 6-10 days, substantially more than the PS
      random oligodeoxynucleotides. Inhibition of BZLF1 appears to be sufficient to
      suppress the induction of EBV replication.

PMID- 8739604
TI  - Selective protection of toxicity of 2',3'-dideoxypyrimidine nucleoside analogs by
      beta-D-uridine in human granulocyte-macrophage progenitor cells.
AB  - beta-D-Uridine protected human granulocyte-macrophage lineage cells in both semi
      solid (granulocyte-macrophage colony-forming units, CFU-GM) and liquid cultures
      against the toxic effects of 3'-azido-3'-deoxythymidine (AZT), 3'-fluoro-3'
      deoxythymidine (FLT) and a combination of AZT and FLT, without impairment of the
      activities of these respective drugs against human immunodeficiency virus (HIV)
      replication. In addition, beta-D-uridine also protected human CFU-GM against
      toxicity of the in vivo AZT metabolite, 3'-amino-3'-deoxythymidine (AMT). Beta-L
      uridine and alpha-D-uridine, two stereoisomers of the natural form, and the base
      uracil, were unable to protect cells against either AZT or FLT toxicity, whereas
      beta-D-uridine-5'-bis(SATE)phosphotriester, a prodrug of beta-D-uridine-5'
      monophosphate, successfully protected cells against AZT toxic effects, suggesting
      that beta-D-uridine needs to be metabolized to its nucleotides to exert a
      pharmacological effect. These data suggest in addition that AZT, FLT and AMT
      share a common target site(s) of toxicity involved in myelosuppression.

PMID- 8739605
TI  - Human immunodeficiency virus type-1 (HIV-1) replication is unaffected by human
      secretory leukocyte protease inhibitor.
AB  - Human secretory leukocyte protease inhibitor (SLPI), a serine protease inhibitor
      found concentrated in secretory fluids, has been postulated to participate in the
      body's natural defense against infection by the human immunodeficiency virus type
      1 (HIV-1) by affecting trypsin-like enzymes on the surface of target cells. SLPI
      was evaluated for potential antiviral activity against laboratory, clinical and
      monocytotropic strains of HIV-1 in human T-cell lines, peripheral blood
      lymphocytes and monocyte/macrophage cultures. SLPI was tested in a single cycle
      of infection assay and under conditions in which SLPI was preincubated both with
      target cells and with virus and then maintained during the virus-to-cell
      adsorption phase and throughout the entire culture period. However, SLPI did not
      exert anti-HIV activity under any experimental conditions, and mechanistic
      studies showed SLPI to have no inhibitory activity on HIV-1 binding, reverse
      transcriptase or protease. Thus, SLPI exhibited no suggestive anti-HIV-1
      activity.

PMID- 8739607
TI  - The influence of signal variation, bias, noise and effect size on statistical
      significance in treatment studies of the common cold.
AB  - Many groups are working on new and improved methods of common cold treatment that
      include antivirals, synthetic viral receptor, compounds which block symptom
      pathways, and combinations of these approaches. Because the common cold syndrome
      is in large part subjective, symptom measurement remains an important parameter
      in evaluating the effectiveness of cold treatments. This review examines the
      features of the experimental and natural cold testing methods that effect
      recognition of illness signal and influence its variance and strength. Also, the
      importance of changes in signal variance and in the magnitude of therapeutic
      effect size as they relate to statistical probability were compared using a
      symptom data set from young adults with experimental rhinovirus colds.

PMID- 8739606
TI  - Correlation of in vivo topical efficacies with in vitro predictions using
      acyclovir formulations in the treatment of cutaneous HSV-1 infections in hairless
      mice: an evaluation of the predictive value of the C* concept.
AB  - The purpose of this study was to carry out an extensive examination of the C*
      concept for prediction of the topical antiviral efficacies of acyclovir (ACV)
      formulations in a hairless mouse model for the treatment of cutaneous herpes
      simplex virus type-1 (HSV-1) infections. This method is based on estimation of
      the free drug concentration at the target site (C*), which is presumed to be the
      basal cell layer of the epidermis. Five different formulations (containing 5%
      ACV) were examined in a finite dose multiple dosing regimen (twice a day
      application) to simulate the clinical situation. For determination of C*, in
      vitro ACV fluxes across the hairless mouse skin were measured in an in vivo-in
      vitro experimental design that approximated the in vivo antiviral treatment
      protocol. Then, the in vivo antiviral efficacies were measured using a 1-day
      delayed (after HSV-1 virus inoculation) 4-day treatment protocol. 10 microL/cm2
      dose of ACV formulation was applied every 12 h for 4 days after which the lesions
      were scored and efficacies were calculated. Our results indicate that, over a
      wide range of efficacies, the predictions based on C* (estimated from the
      experimental fluxes) are in good agreement with the in vivo antiviral efficacies.
      These studies, therefore, support the validity of the C* concept for various ACV
      formulations and suggest that the C* approach has potential for future practical
      situations.

PMID- 8739608
TI  - Antiviral activity of the bicyclam derivative JM3100 against drug-resistant
      strains of human immunodeficiency virus type 1.
AB  - Bicyclams have recently been identified as potent and selective inhibitors of
      human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) replication. The
      prototype of this series, JM3100 exhibits anti-HIV potency at concentrations
      ranging from 0.001 to 0.01 micrograms/ml. JM3100 proved to be active when tested
      against HIV strains resistant to the reverse transcriptase (RT) inhibitors 3'
      azido-3'-deoxythymidine (AZT), 2',3'-dideoxyinosine (DDI), 3TC, alpha APA and
      TIBO, at roughly the same concentrations as for the wild-type strain. The virus
      was passaged in vitro in the presence of increasing concentrations of either TIBO
      or alpha APA alone or in combination with JM3100. The combination between TIBO,
      or alpha APA, and JM3100 delayed the development of TIBO- and alpha APA-resistant
      strains, without emergence of resistance to JM3100. In separate experiments, it
      took more than 60 passages (300 days) in MT-4 cells and 20 passages (140 days) in
      peripheral blood lymphocyte (PBL) cells for the virus to become resistant to
      JM3100. The JM3100-resistant virus showed cross-resistance to sulfated
      polysaccharides such as dextran sulfate (DS), pentosan sulfate (PS), heparin and
      cyclodextrin sulfate (CDS), suggesting that these compounds may share a common
      mechanism of action. Furthermore, the inhibitory effect of JM3100 on virus
      induced syncytium formation was enhanced in the presence of heparin. The results
      presented here provide further support for the bicyclams as attractive candidate
      drugs for the chemotherapy of HIV infections.

PMID- 8739609
TI  - Inhibitors of infectious pancreatic necrosis virus (IPNV) replication.
AB  - In attempts to detect inhibitors of infectious pancreatic necrosis virus (IPNV)
      replication, we have evaluated, by an IPNV plaque inhibition assay, a group of
      compounds that have broad spectrum antiviral activity for both single- and double
      stranded RNA viruses. The inosine monophosphate dehydrogenase (IMP dehydrogenase)
      inhibitors 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) and 5
      ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR), and the orotidine
      monophosphate decarboxylase (OMP decarboxylase) inhibitor 4-hydroxy-3-beta-D
      ribofuranosylpyrazole-5-carboxamide (pyrazofurin), were found to inhibit IPNV
      replication. For EICAR and pyrazofurin the concentrations that inhibited the IPNV
      plaque formation by 50% (EC50) were 0.01 micrograms/ml and 0.5 micrograms/ml,
      respectively. The cytotoxic concentrations required to reduce cell viability by
      50% (CC50) were 50 micrograms/ml and 100 micrograms/ml, respectively, and the
      concentrations that reduced [methyl-3H] thymidine incorporation by 50% (IC50)
      were 0.5-1 and 50 micrograms/ml. Thus, for both compounds the IPNV-inhibitory
      concentration was 50-100 times lower than the concentration that affected DNA
      synthesis in growing cells. EICAR and pyrazofurin seem to be good candidates for
      further evaluation in an in vivo model of IPNV infection.

PMID- 8739610
TI  - The sensation of respiration in men experiencing high-altitude chronic hypoxia.
AB  - Respiratory sensation was studied in seven European lowlanders during a Himalayan
      expedition at over 6000 m. At rest, the ability to detect added inspiratory
      resistive loads can be used to create a sensitivity index P(A) taking response
      bias (B) into account based on Sensory Decision Theory. The data indicate that
      respiratory sensitivity may be involved in successful adaptation to hypoxia.
      Respiratory sensitivity improved during the first stages of exposure to altitude
      and returned to baseline after 17- and 27-day stays under chronic hypoxic
      conditions. The improvement in respiratory sensation could be a primary signal in
      the physiological and psychological adaptation to high altitude and change in
      sensation may reflect the degree of altitude adaptation.

PMID- 8739611
TI  - Mismatch negativity subcomponents and ethyl alcohol.
AB  - Effects of ethanol (0.55 and 0.85 g/kg) on event-related potentials were
      investigated by presenting 50-ms standard and 25-ms deviant pure tones to 9
      social drinkers during a reading task, in a single-blind, placebo-controlled
      paradigm. Whereas the lower ethanol dose had no impact on ERPs with an 0.8-s
      inter-stimulus interval (ISI), it attenuated the N1, P2, and mismatch negativity
      (MMN) amplitudes with a longer ISI of 2.4 s. The higher alcohol dose increased
      the N1 peak latency with both ISIs. It also suppressed the N1 and MMN amplitudes
      with the longer ISI. The MMN suppression did not, however, occur at scalp sites
      below the Sylvian fissure, thus suggesting that ethanol affected only the frontal
      MMN subgenerator. Moreover, the different dose responses of the N1, P2, and MMN
      (subcomponents) to ethanol may indicate that the neurotransmitter systems
      underlying their generation are, to some extent, different.

PMID- 8739612
TI  - Aging, stimulus identification and the effect of probability: an event-related
      potential study.
AB  - Event-related potentials (ERPs) of younger and older subjects were compared in a
      simple reaction time (SRT) and in two GoNogo (20% and 80% target probability)
      tasks. At the T5 location, the NA component (the difference between the ERPs
      elicited by the frequent stimuli in the GoNogo tasks on the one hand, and the
      ERPs in the SRT task on the other hand) emerged earlier in the younger group. The
      N2b was larger in the younger group, and in this group the rare stimuli of the
      80% GoNogo task elicited an enlarged N2. When compared to the older group, the
      stimulus probability in the younger group had a larger effect on the amplitude of
      the late positivity. The results show age-related changes at an early stage of
      the information processing activity, and larger sensitivity of the orienting
      system in the younger subjects.

PMID- 8739613
TI  - Modulation of auditory responses during oddball tasks.
AB  - The modulation of auditory input processing in relation to slow event-related
      potentials was examined in two studies. A steady-state response (SSR) was evoked
      by a stimulus train delivered at 40 Hz. Slow potentials were elicited by an
      oddball task implemented as changes in the pitch of single stimuli within this 40
      Hz train. In study 1, subjects responded to rare targets by means of a button
      press. In study 2, subjects responded to targets by means of a motor response in
      one session and by silent counting in another session. In both studies, the
      oddball task elicited a P300 to targets. SSR amplitude was reduced 100 ms
      following each stimulus, while a second amplitude reduction around 350-400 ms was
      discovered following targets, in particular, following a button press. Parallel
      to SSR amplitude reductions, the latencies between stimulus and subsequent SSR
      peak were reduced. Results indicate that processing of oddball stimuli and motor
      responding alters 'automatic' auditory processing at the level of the primary
      auditory cortex; the second SSR amplitude reduction which develops in parallel to
      P300 might support the hypothesis that slow positive potentials indicate
      widespread (disfacilitation) inhibition of cortical neural excitability.

PMID- 8739614
TI  - Effects of intermodality change and number of training trials on electrodermal
      orienting and on the allocation of processing resources.
AB  - The present experiments examined the hypothesis that the electrodermal orienting
      response elicited by and the processing resources allocated to an intermodality
      change stimulus will vary as a function of the amount of pre-change habituation
      training. Experiment 1 (N = 64) employed a 2 x 2 design in which subjects
      received either 6 or 24 training trials followed by either an intermodality
      change trial or a further trial with the training stimulus. Skin conductance
      responses were measured throughout. Training and test stimuli (visual and
      vibrotactile) were counterbalanced within groups. Intermodality change elicited
      larger responses than did no-change, and in the 24-trial condition, test trial
      responses were larger than those on trial 1 of the habituation series. Experiment
      2 (N = 64) employed the same design and procedure except that reaction time to
      auditory probes presented 300 ms following the onset of some stimuli and during
      some of the intertrial intervals was also measured. The results indicated that in
      the 24-trial condition, but not in the 6-trial condition, probe reaction time on
      the test trial was slower in the Change group than in the No Change group. Probe
      reaction time on the test trial did not exceed reaction time on the first trial
      of habituation. The results are consistent with the view that development of a
      stimulus expectancy is one important factor in producing the intermodality change
      effect.

PMID- 8739615
TI  - Individual differences in cortisol responses to a laboratory speech task and
      their relationship to responses to stressful daily events.
AB  - A Stress Inducing Speech Task was used to investigate the contribution of
      perceived stress, individual traits, and current mood states to individual
      differences in salivary cortisol responses. Additionally, we examined the
      correspondence between laboratory baseline cortisol levels and overall levels in
      daily life, and between cortisol responses to the speech task and a measure of
      stress reactivity to stressful events in daily life. Forty-two 'high stress' and
      forty-five 'low stress' white-collar males completed the speech task and an
      Experience Sampling study, in which stressful daily events and cortisol levels
      were monitored for five days. No association was found between perceived stress,
      trait anxiety, anger, depression, psychosomatic symptoms, coping style or
      personality and cortisol responses to the speech task. Negative mood state at
      baseline was associated with higher cortisol levels at baseline just before, and
      just after, the speech. Laboratory and field cortisol levels were moderately
      correlated, but no association was found between laboratory and field response
      measures. Laboratory baseline levels, but not responses to the speech task, were
      significant predictors of field cortisol levels.

PMID- 8739616
TI  - MPP(+)-induced neurotoxicity in mouse is age-dependent: evidenced by the
      selective inhibition of complexes of electron transport.
AB  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has been demonstrated to
      cause selective neurotoxicity by inhibiting complex I in mitochondria, through
      its toxic metabolite 1-methyl-4-phenylpyridine (MPP+) which is formed during the
      bioactivation of MPTP by monoamine oxidase B. In this report, we have evaluated
      the effect of MPP+ on the 4 mitochondrial respiratory chain complexes by
      incubating brain mitochondria of mice at 3 different age groups with MPP+ (200
      microM) and monitoring enzyme activities of complexes I, II, III, and IV at 5,
      10, 15, 30, 60, and 120 min. Complexes I, III, and IV showed significant
      inhibition within 15 min in all the age groups studied, followed by some recovery
      in enzyme activities upon further incubation for complexes I and IV. However,
      complex II was not affected by MPP+ at any age. Our data suggest that inhibition
      of complexes I, III, and IV by MPP+ efficiently restrict the transport of
      electrons down the respiratory chain which ultimately leads to decreased ATP
      production. This could further aggravate oxidative stress as ATP is required for
      the synthesis of glutathione (GSH), one of the important scavengers of free
      radicals. In this study, inhibition was more severe in mitochondrial preparations
      from older rather than younger mice. Additionally, young animals showed faster
      recovery following inhibition than old animals for complex I. Impaired
      respiratory chain function in older animals compared to younger ones supports the
      hypothesis of accumulation of age-related mitochondrial DNA mutations which
      partly encode for subunits of complexes I, III, and IV. From this study, it seems
      that inhibition of complexes I, III, and IV may be the underlying cause of
      neurotoxicity due to MPP+ which could be intensified by age-associated
      dysfunction of electron transport.

PMID- 8739617
TI  - Comparative effect of IL-2 and IL-6 on morphology of cultured hippocampal neurons
      from fetal rat brain.
AB  - It has become increasingly clear that immune cytokines have an effect on growth
      and differentiation in the nervous system as well as in the immune system. We
      have previously reported that interleukin-2 (IL-2) promotes survival of primary
      cultured neurons from fetal rat brain. In the present study, we investigated the
      effects of IL-2 as well as IL-6, one of the neurotrophic cytokines, on neuronal
      morphology and regeneration after damage in primary cultured hippocampal neurons.
      For neuronal morphology, IL-2 significantly promoted the elongation and branching
      of neurites, but IL-6 enhanced only the elongation. The neurite-elongating effect
      of IL-2 was different from that of IL-6 in terms of both effective concentration
      and maximal effect. In laser beam-damaged neurons, IL-2 significantly increased
      both the number and the length of branches emerging from the proximal part of
      damaged neurite. IL-2 also increased the length and the number of non-damaged
      neurites. IL-6, however, did not affect any of these parameters in damaged
      neurons. These results suggest that IL-2 and IL-6 modulate neuronal morphology
      through distinct mechanisms.

PMID- 8739618
TI  - Choroid plexus taurine transport.
AB  - The putative osmoregulatory agent, taurine, is lost from the brain during hypo
      osmotic stress or ischemia, but the regulatory mechanisms involved in this loss
      have not been fully elucidated. In this study, we have examined taurine transport
      by the isolated rat choroid plexus, one element of the brain-blood interface, and
      examined how it may be regulated as part of brain volume regulation. Choroid
      plexus taurine uptake was Na- and Cl-dependent with a Vmax and Km of 6.5 +/- 0.3
      pmol/mg/min and 232 +/- 33 microM. The latter is substantially greater than the
      normal CSF taurine concentration and this may be important in removing taurine
      released into the CSF during parenchymal cell swelling. Taurine uptake also
      appears calmodulin dependent as it was reduced by 84 and 91% in the presence of
      25 microM trifluoperazine and 100 microM W-7, two calmodulin inhibitors. Taurine
      efflux from choroid plexus was stimulated by trifluoperazine, taurine, and hypo
      osmotic stress. The latter two effects were reduced by niflumic acid, suggesting
      that taurine and hypo-osmotic stress act on the same pathway. The stimulation of
      efflux by hypo-osmotic stress decreased with time, whereas the effect of external
      taurine was sustained. If this efflux pathway is involved in the movement of
      taurine from choroid plexus to blood, these results suggest that changes in
      extracellular taurine may be more important than the direct effect of hypo
      osmolality in the long-term loss of taurine from the brain.

PMID- 8739619
TI  - Nitric oxide synthase inhibitors produce phencyclidine-like behavioral effects in
      pigeons.
AB  - The present study assessed the ability of nitric oxide synthase (NOS) inhibitors
      to produce PCP-like behavioral effects in pigeons. Food-restricted pigeons were
      trained to discriminate between PCP (1.0 mg/kg, i.m.) from saline in a two-key
      operant procedure. NOS inhibitors 7-nitroindazole (7-NI) and N omega-nitro-L
      arginine methyl ester (L-NAME) produced PCP-like discriminative stimulus effects.
      7-NI (17.8 mg/kg, i.m.) completely generalized to PCP. L-NAME (320-1000 mg/kg)
      produced partial generalization to PCP. D-NAME, the enantiomer of L-NAME, did not
      produce PCP-appropriate behavior. L-NAME was approximately 200-times more potent
      i.c.v., but did not fully generalize to PCP. Both NOS inhibitors were effective
      in producing catalepsy, which is an effect commonly produced by competitive and
      uncompetitive NMDA antagonists. 7-NI (32 mg/kg) produced catalepsy in all
      subjects, whereas L-NAME (3200 mg/kg) produced catalepsy in 50% of the subjects,
      D-NAME did not produce catalepsy. Pretreatment with L-arginine (32-3200 mg/kg)
      prevented the PCP-like discriminative stimulus and cataleptic effects of 7-NI
      (17.8-32 mg/kg), demonstrating that 7-NI produced PCP-like effects through
      blockade of NO synthesis. The current studies reveal that NOS inhibitors induced
      two behavioral actions, discriminative stimulus effects and catalepsy, that are
      very selective for NMDA antagonists in pigeons.

PMID- 8739620
TI  - Perineuronal microglial reactivity following proximal and distal axotomy of rat
      rubrospinal neurons.
AB  - Microglial reactivity in the red nucleus of rats was studied following upper
      cervical and lower thoracic rubrospinal tractotomy using the lectin binding
      method. Following axotomy, the contralateral nucleus containing the axotomized
      neurons was identified using the retrograde tracer Fast blue. It was subdivided
      into dorsomedial (DM) and ventrolateral (VL) portions known to project to the
      cervical and lumbar spinal cord, respectively. Lectin-labeled microglial cells
      and processes on the contralateral as well as in the ipsilateral nucleus were
      then quantified. An early and a late increase in microglial reactivity was
      observed in the nucleus at 2-5 days and 2-8 weeks following thoracic and cervical
      tractotomy with the latter producing a more pronounced reactivity. In rats
      subjected to thoracic axotomy, a similar microglial increase also occurred in the
      intact contralateral DM nuclear area suggesting the possible action of diffusable
      factor(s) that might have triggered the microglial activation from the axotomized
      VL nuclear area. The uninjured ipsilateral nucleus also exhibited a similar
      pattern of microglial reactivity irrespective of the number of ipsilaterally
      projecting neurons following both cervical and thoracic axotomy. This could have
      been elicited by the retrograde influence from the denervated targets carried by
      the intact rubrospinal fibers of the opposite side since many of them in fact
      terminate bilaterally (Antal, M. et al., J. Comp. Neurol., 325 (1992) 22-37). In
      all the axotomized or intact nucleus, microglial processes did not appear to
      surround neuronal cell bodies. The characteristic responses of microglial cells
      in the red nucleus may be related to the failure of rubrospinal neurons to
      regenerate following the severance of their axons.

PMID- 8739621
TI  - Neuropathology of synthetic beta-amyloid peptide analogs in vivo.
AB  - Considerable evidence exists demonstrating that beta-amyloid protein and its
      fragments 1-40 and 25-35 (beta (25-35)) are neurotoxic to cells in the rat
      hippocampus both in culture and in vivo. This neurotoxicity has been correlated
      to the aggregational state of the peptides. Previously we have shown that beta
      (25-35) produces a cavitational lesion in rat hippocampus and also reduces the
      enzyme or transmitter expressions in two subcortical structures whose axons
      project to the hippocampus: the locus coeruleus (LC) and the medial septum. In
      the present study, we further investigated the amino acid sequence that might be
      responsible for these effects. A series of synthetic peptide analogs of beta (25
      35) with glycine substituted for serine, asparagine, lysine and methionine at
      positions 26, 27, 28 and 35, respectively, were injected at a 3 nmol dosage into
      the rat hippocampus once a week for 2 weeks. The damage to the hippocampus and
      immunohistochemistry of the LC and medial septum were examined 1 week following
      the second treatment. All of the synthetic peptides with glycine substitution
      produced damage to the hippocampal tissue. This damage was similar to that seen
      with beta (25-35). However, the reduction of enzyme expressions in the LC and
      medial septum was less from these substituted peptides than from that of beta (25
      35). While beta (25-35) application resulted in a similar reduction of tyrosine
      hydroxylase (TH) and glutamate (Glu) immunoreactivities in the LC, only TH was
      significantly reduced in the substituted peptide groups. The least reduction of
      TH and Glu immunoreactivities in the LC was observed in rats treated with
      peptides in which glycine replaced either lysine or methionine. In the basal
      forebrain medial septum, the application of beta (25-35) resulted in a marked
      decrease in choline acetyltransferase (ChAT) immunoreactivity. This reduction was
      found to be less by each of the synthetic peptides. These results suggest that
      the biological activity of beta (25-35) is sensitive to changes in the primary
      structure of the peptide. Among the 4 amino acid residues examined, lysine and
      methionine at positions 28 and 35 appear to play more important roles in
      determining the action of beta (25-35).

PMID- 8739622
TI  - Systemic ketamine attenuates nociceptive behaviors in a rat model of peripheral
      neuropathy.
AB  - The efficacy of ketamine (KET), a non-competitive NMDA receptor-channel blocker,
      was assessed in relieving nociceptive behaviors in neuropathic rats with tight
      ligations of the L5 and L6 spinal nerves. The antinociceptive effects of KET were
      dose- and time-dependent. A systemic injection of 0.01 mg/kg KET transiently (15
      30 min) attenuated several nociceptive behaviors, including mechanical allodynia
      and hyperalgesia, cold allodynia, spontaneous pain, and cold stress-induced pain.
      Treatment with 1.0 mg/kg KET consistently decreased all nociceptive behaviors for
      45-75 min, without noticeable side effects. Higher doses (25 and 50 mg/kg)
      provided longer lasting relief: however, these doses resulted in transient motor
      impairment which lasted for 15-30 min post-injection. Systemic KET was most
      effective in decreasing the behavioral signs of mechanical allodynia and
      hyperalgesia, followed by cold allodynia, cold stress-induced pain, and
      spontaneous pain. The present results demonstrate that blockade of NMDA receptors
      effectively alleviates nociceptive behaviors in a rat model of peripheral
      neuropathy, substantiating the important role of these receptors in the central
      sensitization that underlies the maintenance of neuropathic pain. In addition,
      the ability of KET to reduce significantly a variety of nocifensive behaviors
      suggests that this clinically safe drug could be used in pain management for
      neuropathic patients.

PMID- 8739623
TI  - Reciprocal synaptic connections between neurotensin- and tyrosine hydroxylase
      immunoreactive neurons in the mediobasal hypothalamus of the guinea pig.
AB  - Neurotensin (NT) and dopamine are two neurotransmitters which are present in the
      hypothalamus of mammals and are often distributed in identical areas. In
      particular, in the periventricular anterior hypothalamus and in the arcuate
      nucleus, images of apposition between perikarya and fibers containing dopamine or
      neurotensin have frequently been observed at the light microscope level. The aim
      of this study was to answer, at the ultrastructural level in the A12 and A14
      catecholaminergic cell groups, the question as to the existence of the possible
      synaptic nature of such contacts. To this end, NT and tyrosine hydroxylase (TH)
      were simultaneously visualized using double pre-embedding immunocytochemical
      methods. In the A12 arcuate area, synaptic contacts were demonstrated between TH
      immunoreactive terminals and NT-labeled perikarya and dendrites. The opposite
      pattern, i.e., NT-stained terminals synapsing onto TH-positive neurons, was also
      observed. In contrast, only NT synaptic inputs onto TH-stained cell bodies could
      be demonstrated in the hypothalamic periventricular nucleus. In addition,
      immunoreactive terminals stained for NT or TH were observed to make synaptic
      contacts with perikaryal profiles stained for the same antigen. These results
      demonstrate a strong synaptic NT input onto the dopaminergic neurons of the
      mediobasal hypothalamus and suggest a reciprocal influence, at least in part, of
      catecholaminergic terminals on arcuate NT-containing neurons.

PMID- 8739624
TI  - Calbindin-D28k-immunoreactivity in the trigeminal ganglion neurons and molar
      tooth pulp of the rat.
AB  - The cell body size and coexpression of carbonic anhydrase (CA), calretinin (CR)
      and calcitonin gene-related peptide (CGRP) of primary neurons with calbindin-D28k
      (CB) was examined in the trigeminal ganglion (TG) of the rat. CB-immunoreactive (
      ir) cells were mostly large and preferentially distributed in the maxillary and
      mandibular divisions of the TG. 48% of CB-ir TG cells exhibited enzyme CA
      activity. 10% of CB-ir TG cells contained CR-ir. Most TG cells coexpressing CB-
      and CR-irs were localized to the maxillary and mandibular divisions and exhibited
      CA activity. 6.5% of CB-ir TG cells coexisted with CGRP-ir. 46% of TG cells
      coexpressing CB and CGRP exhibited CA activity. The innervation of the molar
      tooth pulp by CB-ir TG primary neurons was also examined. CB-ir thick and smooth
      nerve fibers projected from the root pulp to the pulp horn and the roof of the
      pulp chamber, where they became thinner and rarely entered the subodontoblastic
      layer. However, they could not be traced to the odontoblastic layer, predentin or
      dentine. The distribution pattern of CB-ir pulpal fibers was different from that
      of CR-ir ones. The trigeminal neurons cells retrogradely labeled with fast blue
      (FB) from the maxillary molar tooth pulp contained CB- and CR-irs. 23% and 1% of
      the labeled cells were immunoreactive for CB and CR, respectively. The
      coexpression of CB- and CR-immunoreactivities (-irs) in FB-labeled cells was
      negligible. An immunoelectron microscopic method revealed that 21% of pulpal
      nerve fibers were immunoreactive for CB, and that all CB-ir nerve fibers in the
      root pulp were myelinated. The present study indicated that the tooth pulp
      primary neurons contained CB-ir but did not coexpress CB- and CR-irs and that
      these neurons projected their myelinated axons to the pulp.

PMID- 8739625
TI  - Properties of Na(+)-dependent K+ conductance in the apical membrane of frog taste
      cells.
AB  - Na(+)-dependent K+ conductance observed in apical membrane of isolated bullfrog
      taste cells was analyzed using various modifications of the patch clamp method.
      When the apical receptive membrane of a taste cell was exposed to 0.5 M NaCl
      using a pipette perfusion method, an inward current appeared in the cell-attached
      patch membrane. The permeability ratio of Na+ to K+ (P(Na)/P(K)) calculated from
      the reversal potential was 0.3. When an outside-out patch from the receptive
      membrane was exposed to 0.25 M NaCl solution, two types of K+ channel, whose
      conductance were 35.8 and 9.4 pS respectively, were activated. These channels
      were reversibly activated by increasing internal Na+ concentration. In the whole
      cell configuration, the outward current evoked by a voltage ramp from -80 to 80
      mV was significantly suppressed by replacement of Na+ by N-methyl-D-glucamine+
      (NMDG+). The Na(+)-dependent outward current was blocked by 10 mM BaCl2, with
      positive shift of the zero-current potential in the whole cell recordings,
      indicating that the outward current including Na(+)-dependent K+ component
      contributes to maintenance of the resting potential. These results suggest that
      small conductance Na(+)-dependent K+ channels, which are also permeable to Na+,
      are involved in salt signal transduction in frog taste cells.

PMID- 8739626
TI  - Medial prefrontal cortical D1 receptor modulation of the meso-accumbens dopamine
      response to stress: an electrochemical study in freely-behaving rats.
AB  - Voltammetry was used to study the role of prefrontal cortex (PFC) dopamine (DA)
      in modulating the nucleus accumbens (NAcc) DA response to stress. Signal
      increases elicited in NAcc by 15 min of restraint were monitored in freely
      behaving rats following intra-PFC microinjections of D1 and D2 receptor-selective
      drugs. The exact site of injection was first determined by assessing the
      electrochemical response to stress at two dorsal-ventral levels of PFC.
      Consistent with previous reports, a pronounced stress response was observed
      ventrally at sites within the infralimbic PFC but not dorsally within the
      superficial layers of PFC. When microinjected into the infralimbic PFC, the D1
      receptor antagonist SCH 23390 significantly enhanced the NAcc stress response.
      While the D1 receptor agonist SKF 38393 tended to decrease the NAcc stress
      response, it failed to do so reliably. Neither sulpiride (D2 receptor antagonist)
      nor quinpirole (D2 receptor agonist) had a significant effect. Finally, systemic
      administration of the selective DA uptake inhibitor GBR 12909 dose-dependently
      potentiated stress-induced signal increases in NAcc and in PFC, indicating that
      the electrochemical responses to stress in both regions were due primarily to
      increases in extracellular DA levels. Together, these data add to other evidence
      indicating that the PFC exerts an inhibitory influence on subcortical DA
      transmission. Specifically, the present results suggest that the NAcc DA response
      to stress is dampened by the concurrent activation of meso-PFC DA neurons and
      that this action is mediated, at least in part, by D1 receptors in PFC.

PMID- 8739627
TI  - Effects of ether lipid 1-O-octadecyl-2-methoxy-rac-glycero- 3-phosphocholine and
      its analogs PAF and CPAF on the release of nitric oxide in primary cultures of
      rat astrocytes.
AB  - Ether lipid 1-O-octadecyl-2-O-methoxy-rac-glicero-3-phosphocholine (ET-18-OCH3)
      is an immunomodulator with antineoplastic activity. Its analog compounds PAF and
      CPAF share some of its biological effects. In our experiments, even very small
      amounts of ET-18-OCH3 released a remarkable quantity of nitric oxide (NO) from
      rat astrocytes cultured in vitro. The NO biosynthesis was inhibited by
      pretreatment with the antagonist BN 50730. The effect of ET-18-OCH3 was greater
      than that of the LPS inducer. PAF did not produce NO, even at high doses, while
      the nonmetabolizable CPAF only induced a significant release of NO from 12
      micrograms/ml onwards. These results demonstrate that ET-18-OCH3 is functionally
      active also in astrocyte cultures. Stimulation of NO biosynthesis is of a great
      value on account of its the known effect as a neurotransmitter, potentiator of
      immune defences and possible modulator of cerebral circulation.

PMID- 8739628
TI  - NMDA as well as non-NMDA receptors mediate the neurotransmission of inspiratory
      drive to phrenic motoneurons in the adult rat.
AB  - The neurotransmission of bulbospinal respiratory drive is believed to involve
      primarily non-NMDA receptors located in the phrenic motonucleus (PMN). This
      conclusion is based on studies carried out mainly on in vitro brainstem-spinal
      cord preparations of the neonatal rat. The present study was undertaken to
      investigate the transmitter/receptor mechanisms in the PMN which are involved in
      the neurotransmission of inspiratory drive, using an in vivo adult rat model.
      Microinjections of glutamate, NMDA and AMPA into the PMN elicited an increase in
      the phrenic nerve (PN) background discharge. These injections did not alter
      significantly the frequency of spontaneously occurring PN bursts confirming that
      mechanisms responsible for respiratory rhythm reside in the supraspinal
      structures. Microinjections of an NMDA receptor blocker (AP-7), in concentrations
      that did not alter the responses to a non-NMDA receptor agonist (AMPA), reduced
      the PN amplitude significantly. Similarly, microinjections of a potent non-NMDA
      receptor blocker (NBQX), in concentrations that did not alter responses to NMDA,
      reduced the PN amplitude significantly. Sequential microinjections, within an
      interval of 5 min, of AP-7 and NBQX into the PMN, resulted in a dramatic
      reduction in the spontaneous PN bursts. The reduction of PN amplitude started
      immediately after the microinjection of AP-7 and NBQX, either alone or in
      combination, and reached a maximum within 5-10 min. These results indicate that,
      unlike in the neonatal rat, both NMDA and non-NMDA receptors located in the PMN
      play a significant role in the neurotransmission of the inspiratory drive in the
      adult rat.

PMID- 8739629
TI  - Effects of testosterone upon MPTP-induced neurotoxicity of the nigrostriatal
      dopaminergic system of C57/B1 mice.
AB  - We have recently reported that treatment of gonadectomized female and male C57/B1
      mice with the gonadal steroid hormone, estrogen, reduced nigrostriatal
      dopaminergic neurotoxicity resulting from the Parkinson's-like inducing agent 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the present report we
      examined whether the predominantly male gonadal steroid hormone, testosterone,
      would similarly modulate MPTP-induced neurotoxicity. Male C57/B1 mice were
      assigned to one of the following five treatment conditions: (1) Intact, (2)
      Orchidectomized, (3) Intact + MPTP, (4) Orchidectomized + Testosterone + MPTP and
      (5) Orchidectomized + MPTP. Corpus striatal and olfactory tubercle dopamine.
      DOPAC and norepinephrine concentrations were determined from the animals within
      each of the five treatment conditions. Orchidectomy alone failed to alter
      striatal dopamine and DOPAC concentrations, with levels obtained being similar to
      that of Intact animals. MPTP treatment significantly reduced striatal reduced
      striatal dopamine and DOPAC concentrations, regardless of hormonal condition of
      the animal. Similar results were obtained for olfactory tubercle determinations,
      with the exception that DOPAC levels from Orchidectomized mice were significantly
      greater than Intact males. No significant differences were obtained for
      norepinephrine within either brain area sampled. These results show that unlike
      estrogen, testosterone is devoid of any capacity to modulate nigrostriatal
      dopaminergic neurotoxicity resulting from MPTP. These findings may be related to
      the gender differences which exist in the prevalence of Parkinson's disease.

PMID- 8739630
TI  - Effects of social isolation rearing on learning in the Morris water maze.
AB  - Impaired learning has been shown as a consequence of isolation-rearing in a
      variety of paradigms. However, there are situations in which learning in
      isolation-reared rats is enhanced or unimpaired compared to socially reared rats.
      The present experiments investigated the effects of isolation rearing on place
      navigation in the Morris water maze. Two complementary paradigms were studied:
      isolation and socially reared rats were exposed to the water maze either without
      drug pretreatment or following systemic administration of scopolamine. Two
      conditions were examined: place learning and reversal learning. Male Lister
      hooded rats were either housed singly (isolation reared) or in groups of four
      (social reared) from weaning at 21 days of age. Six weeks later place learning
      and reversal learning were determined using the Morris water maze. The time taken
      to locate the submerged island (escape latency) was used as the measure of
      learning ability. The results showed that place learning, and reversal learning
      were enhanced in isolation reared rats compared to socially reared controls.
      Pretreatment with scopolamine (0.3 and 0.5 mg/kg, i.p.) produced a dose-related
      cognitive deficit as shown by an increase in the escape latency. Scopolamine (0.3
      mg/kg) impaired both place and reversal learning but this was less pronounced in
      isolation compared to socially-reared rats. These results suggest that rearing in
      isolation may enhance spatial learning though central cholinergic mechanisms.

PMID- 8739631
TI  - Trigeminal-parabrachial connections: possible pathway for nociception-induced
      cardiovascular reflex responses.
AB  - Noxious stimulation of dental nerves elicits marked changes in cardiovascular
      function. In order to investigate central pathways mediating reflex changes in
      cardiovascular activity, immunohistochemical localization of cells expressing the
      immediate-early gene, c-fos, was used to identify central nervous responding to
      noxious electrical stimulation of mandibular, incisor tooth dentin or chemical
      (capsaicin) stimulation of tooth pulp in the anesthetized rat. Injections of
      Fluoro-Gold were made in the lateral parabrachial region to identify efferent
      projections from the spinal trigeminal nucleus. Electrical and chemical
      stimulation produced similar patterns of Fos-positive neurons in the spinal
      trigeminal nucleus: subnuclei caudalis, interpolaris and oralis. Fos-positive
      neurons were most dense in laminae I and II of the dorsomedial subnucleus
      caudalis with fewer Fos-positive neurons located in the interpolaris and oralis
      subnuclei. Sham stimulation of tooth dentin and control vehicle injections into
      the tooth pulp resulted in either a few weakly stained or no Fos-positive neurons
      in the spinal trigeminal nucleus. Cell bodies double labeled with Fluro-Gold
      following injections into the parabrachial region and Fos-protein subsequent to
      electrical stimulation of incisor tooth were present in all three subnuclei of
      the spinal trigeminal nucleus. The largest number of Fos-positive neurons with
      efferent projections to the lateral parabrachial region were located in
      subnucleus caudalis (32.2 +/- 5.3 S.E.M.) and fewer were located in the
      interpolaris (0.4 +/- 0.4 S.E.M.) and oralis (19.8 +/- 3.5 S.E.M.) subnuclei. The
      results demonstrate that nociceptive dental input received by the three subnuclei
      of the spinal trigeminal nucleus, particularly the subnucleus caudalis, is
      relayed to the lateral parabrachial nucleus.

PMID- 8739632
TI  - Thyrotropin-releasing hormone immunoreactive boutons form close appositions with
      medullary expiratory neurons in the rat.
AB  - The aim of the present study was to assess the size of the input from TRH
      immunoreactive varicosities to medullary respiratory neurons in the Botzinger
      complex and caudal ventral respiratory group. Neurobiotin was intracellularly
      injected into seven neurons in the Botzinger complex, between 0.4 and 0.9 mm
      caudal to the facial nucleus. Five of the seven Botzinger neurons had extensive
      local axonal projections, with bouton-like varicosities clustered predominantly
      between their somata and the nucleus ambiguus. Seven neurons in the caudal
      ventral respiratory group, located between 1.6 and 2.4 mm caudal to the facial
      nucleus, were also labelled. All but one caudal respiratory neurons had no, or
      very few, medullary collaterals. TRH immunoreactive fibres were seen in many
      medullary nuclei, including the ventral reticular formation. Botzinger neurons
      were closely apposed by an average of 29 +/- 8 TRH immunoreactive boutons/neuron
      (mean +/- S.D., n = 7). In contrast, caudal ventral respiratory group neurons
      were apposed by only 5 +/- 3 TRH immunoreactive boutons/neuron (n = 7). Botzinger
      neurons form many intramedullary and bulbospinal inhibitory connections with
      premotoneurons and motoneurons that are important in the timing, amplitude and
      shape, of respiratory activity. Our findings suggest a role for endogenous TRH
      containing neurons in modulating the activity of inhibitory Botzinger neurons and
      neurons in the caudal ventral respiratory group. The significance of the apparent
      difference in size of this input remains to be determined.

PMID- 8739633
TI  - Protein kinase C and mouse sciatic nerve regeneration.
AB  - We have studied the role of protein kinase C (PKC) in peripheral nerve
      regeneration by using the cultured adult mouse sciatic nerve, which displays
      regrowth of sensory axons under serum-free conditions. By the use of
      immunohistochemistry we show that one of the isoforms of PKC, PKC beta, is
      present in the nerve cell bodies of normal nerves and is upregulated after
      injury. In spite of this, the specific PKC inhibitor chelerythrine at 5 microM, a
      concentration well above its IC50 value for PKC, failed to reduce the outgrowth
      distance of new axons. This was not due to impermeability of the drug, since the
      same concentration caused a clear reduction of the injury-induced proliferation
      of Schwann cells in the crush region. Likewise, HA-1004, an inhibitor of cyclic
      nucleotide-dependent protein kinases, also lacked effect on outgrowth when used
      on its own, even at very high concentrations (100 microM). In contrast, outgrowth
      was significantly reduced when 5 microM chelerythrine and 5 microM HA-1004 were
      used in combination. In conclusion, the present results suggest that PKC-activity
      is important but not indispensable for the regeneration process. Successful
      completion of the latter could be achieved by several, perhaps redundant,
      phosphorylation systems.

PMID- 8739634
TI  - Biphasic actions of the benzodiazepine receptor inverse agonist RU34347 in the
      rat cerebellar slice.
AB  - We have characterised the biphasic response of the benzodiazepine receptor
      inverse agonist RU34347 in the rat cerebellar slice preparation using
      extracellular electrophysiological recordings from Purkinje cells. RU34347 (10 fM
      10 nM) produced an increase in GABA(A)-mediated inhibition at between 10 fM and
      10 nM, a response normally associated with benzodiazepine agonists. This response
      was biphasic, being dose dependent between 10 fM and the peak effect at 10 pM,
      and inversely related to concentration between 100 pM and 10 nM. Associated with
      this increase in inhibition was a decrease in firing rate, also showing a
      biphasic concentration-response relationship. The agonist-like response was
      composed of two elements, an initial increase occurring after 5 min followed by a
      slow decline over the next 20 min. This second, declining, phase was more evident
      at higher concentrations of RU34347. The peak effect seen at 10 pM was fully
      antagonised by 1 microM flumazenil, a benzodiazepine receptor antagonist. This
      concentration of flumazenil also antagonised the decrease in firing rate induced
      by 10 pM RU34347. The response to 10 nM RU34347 was further characterised since
      the largest second phase decline was demonstrated at this concentration. 10 nM
      flumazenil fully antagonised the second, declining, phase of the response, but
      not the magnitude of the initial increase. A partial antagonism of the peak
      effect was seen with 1 microM flumazenil, and a full antagonism at 10 microM
      flumazenil. This effect was similar to that observed with Ro15-4513 in a previous
      study. Therefore, we investigated the binding of RU34347 to diazepam-insensitive
      benzodiazepine receptors. [3H]Ro15-4513 was displaced by Ro15-4513, flumazenil
      and Ro19-4603, but not by RU34347. Therefore, although the electrophysiological
      data correlate well with that previously reported for Ro15-4513, RU34347 does not
      displace Ro15-4513 binding at the diazepam-insensitive benzodiazepine receptor.
      Therefore, either both ligands bind to complimentary sites on the same receptor
      complex, or both induce a similar physiological response through an action on
      different receptors.

PMID- 8739635
TI  - Differences in striatal extracellular amino acid concentrations between Wistar
      and Fischer 344 rats after middle cerebral artery occlusion.
AB  - We hypothesized that the interstrain difference between Wistar and Fischer-344
      (F344) rats in cerebral infarction volume after proximal middle cerebral artery
      (MCA) occlusion might be explained by differences in excitotoxicity between both
      rat strains. Using microdialysis we measured during a 5 h period after MCA
      occlusion the release of aspartate, glutamate and taurine in the cerebral cortex
      and the striatum. The volume of striatal infarction was comparable in Wistar and
      F344 rats. We found, however, in Wistar rats a significantly higher striatal
      efflux of aspartate and glutamate than in F344 rats, whereas the striatal taurine
      efflux was of a similar magnitude in the two strains. Because of the (variably)
      smaller volume of cortical infarction in Wistar rats (than that in F344), the
      location of the microdialysis probe-membrane with respect to the area of cortical
      infarction differed between Wistar rats. Hence, a reliable comparison between the
      quantitative amount of amino acids in the dialysate from the cortical probes of
      both rat strains could not be made. These results, demonstrating differences in
      striatal excitotoxicity between Wistar and F344 rats after MCA occlusion, are the
      first to show interstrain differences in striatal pathophysiology of focal
      ischemia between these normotensive rat strains. They do however not explain why
      MCA occlusion results in a significantly different volume of cortical infarction
      between Wistar and F344 rats. The F344 strain will probably show in a more
      sensitive way, as compared to Wistar rats, neuroprotective effects of agents that
      diminish excitotoxic damage during focal cerebral ischemia.

PMID- 8739636
TI  - Short-term stimulation-induced decreases in brown fat temperature.
AB  - Electrical stimulation of the ventromedial hypothalamus (VMH) has been shown to
      activate brown adipose tissue (BAT) thermogenesis; we hypothesized that
      functional links between the VMH and other hypothalamic areas may serve to
      regulate intrinsic VMH control of brown fat heat production. Moveable electrodes
      were implanted in regions surrounding the VMH in adult male rats in order to
      assess any acute effect of activation of these structures alone on brown fat
      temperature. Stimulation in the area of the ventral lateral thalamic nucleus and
      the zona incerta (ZI) elicited a 0.2 to 0.8 degrees C drop from brown fat
      baseline temperature in 48 of 55 rats; the effective sites in the ZI area are
      restricted to the actual band of the nucleus. Application of the alpha-adrenergic
      blocker phentolamine prior to restimulation of active sites yielded mixed
      results; these findings are compatible with a role for the vasoconstrictive
      action of alpha-adrenergic receptors in the regulation of BAT temperature drops.
      The mechanisms underlying thermoregulatory responses or diurnal temperature
      cycling may provide a physiological context for the findings reported here.

PMID- 8739637
TI  - Sensorimotor impairments in Wistar Kyoto rats with cerebral infarction, induced
      by unilateral occlusion of the middle cerebral artery: recovery of function.
AB  - Wistar Kyoto (WKY) rats with cerebral infarction induced by permanent unilateral
      occlusion of the middle cerebral artery (MCA) and sham-operated rats were tested
      in a series of simple behavioral test 2, 16 and 37 days after surgery. In
      addition, the motility of the animals was measured over a period of 62 h, after
      the third test series. A subset of the tests appeared to be suitable to assess
      the effects of cerebral infarction, namely, grasping reflex of contralateral
      hindpaw, circling behavior, forelimb flexion, hindlimb flexion, and latency to
      fall off a square bridge. Except for the impaired grasping reflex of the
      contralateral hindpaw, there was spontaneous complete recovery of function by the
      third test session, 37 days after surgery. Some of the other tests might not have
      been sensitive enough to detect the effects of the unilateral MCA-occlusion (MCA
      O) on behavior. Moreover, the WKY rats were very inactive in some of the tests,
      so that reliable scoring of the effects was not always possible. A rat strain
      other than the WKY strain might be more suitable to study the behavioral
      consequences of MCA-O.

PMID- 8739638
TI  - Reoxygenation of anoxic peripheral nerve myelinated axons promotes re
      establishment of normal elemental composition.
AB  - Previously we have shown that in vitro anoxia of rat peripheral nerve myelinated
      axons causes sequential deregulation of axoplasmic Na, K and Ca; i.e., an initial
      influx of Na and loss of K is coupled to subsequent Ca accumulation [7]. In the
      present study, we examined the ability of PNS axons to recover normal elemental
      composition following oxygen deprivation. Thus, electron probe X-ray
      microanalysis was used to determine the effects of post-anoxia reoxygenation on
      the concentrations of elements (i.e., Na, K, Cl, Ca, Mg, P and S) in rat
      posterior tibial nerve myelinated axons and Schwann cells. Results indicate that
      following 180 min of anoxia, peripheral nerve reoxygenation (60 and 120 min)
      promoted progressive recovery of normal elemental composition in axoplasm and
      mitochondria of small, medium and large diameter tibial nerve fibers. Our
      observations also indicate that small axons recovered normal elemental
      concentrations more rapidly than larger counterparts. Schwann cells and myelin
      exhibited only modest elemental disruption during anoxia from which reoxygenation
      promoted full reparation. The ability of peripheral nerve axons to restore normal
      elemental composition during post-anoxia reoxygenation is in marked contrast to
      the exacerbation of elemental deregulation which ensued during in vitro
      reoxygenation of anoxic rat CNS fibers [14]. This differential response to
      reoxygenation represents a fundamental difference in the pathophysiology of
      myelinated axons in the CNS and PNS.

PMID- 8739639
TI  - What are the roles of substance P and neurokinin-1 receptors in the control of
      negative chronotropic or negative dromotropic vagal motoneurons? A physiological
      and ultrastructural analysis.
AB  - Recent data indicate that there is a cardiotopic organization of negative
      chronotropic and negative dromotropic neurons in the nucleus ambiguus (NA).
      Negative dromotropic neurons are found in the rostral ventrolateral NA (rNA-VL),
      negative chronotropic neurons are found in the caudal ventrolateral NA (cNA-VL),
      and both types of neurons are found in an intermediate level of the ventrolateral
      NA (iNA-VL). Substance P (SP) immunoreactive nerve terminals synapse upon
      negative chronotropic vagal motoneurons in the iNA-VL, and SP microinjections in
      the NA cause bradycardia. In the present report we have attempted to: (1) define
      the type of tachykinin receptor which mediates the negative chronotropic effect
      of SP microinjections into the iNA-VL; (2) define the physiological effect of
      microinjections of a selective SP agonist into the rNA-VL on atrioventricular
      (AV) conduction: and (3) find ultrastructural evidence for synaptic interactions
      of SP-immunoreactive nerve terminals with negative dromotropic vagal motoneurons
      in the rNA-VL. Microinjections of the excitatory amino acid glutamate (Glu) into
      the iNA-VL to activate all local vagal preganglionic neurons caused both
      bradycardia and a decrease in the rate of AV conduction. Injections of the
      selective neurokinin-1 (NK-1) receptor agonist drug GR-73632 also caused
      bradycardia, however the rapid onset of agonist induced desensitization prevented
      an evaluation of potential effects on AV conduction in the iNA-VL. These data
      suggest that the SP-induced bradycardia which can be elicited from the NA is
      mediated, at least in part, by NK-1 receptors. Microinjections of Glu into the
      rNA-VL caused a decrease in AV conduction without an effect on cardiac rate. On
      the other hand, GR-73632 microinjections into rNA-VL did not affect AV
      conduction. Following injections of the beta subunit of cholera toxin conjugated
      to horseradish peroxidase (CTB-HRP) into the left atrial fat pad ganglion which
      selectively mediates changes in AV conduction, retrogradely labeled neurons were
      histochemically visualized in the rNA-VL. These tissues were subsequently
      processed for the simultaneous immunocytochemical visualization of SP, and
      examined by electron microscopy. Histochemically labeled neurons were large,
      multipolar, with abundant cytoplasm containing large masses of rough endoplasmic
      reticulum, and exhibited distinctive dendritic and somatic spines. Unlabeled
      nerve terminals were noted to form either asymmetric or symmetric synapses with
      dendrites, dendritic spines, and perikarya of histochemically labeled neurons. SP
      immunoreactive nerve terminals were also detected in the rNA-VL. SP terminals
      typically contained numerous small pleomorphic vesicles, multiple large dense
      core vesicles, and several mitochondria, and they synapsed upon unlabeled
      dendritic profiles. A total of 154 SP-immunoreactive nerve terminals were
      observed on photomicrographs of tissues which also contained histochemically
      labeled profiles. None made an identifiable synapse with a retrogradely labeled
      profile on the sections examined. In summary, both physiological and
      ultrastructural data indicate that SP terminals in the iNA-VL do modify the
      output of negative chronotropic vagal motoneurons. This effect is mediated by NK
      1 receptors. On the other hand both physiological and ultrastructural data
      indicate that SP terminals in the rNA-VL do not modify the output of negative
      dromotropic vagal motoneurons. Therefore different mechanisms (neurotransmitters
      or receptors) mediate the central vagal control of cardiac rate and AV
      conduction.

PMID- 8739640
TI  - ATP receptor activation potentiates a voltage-dependent Ca channel in hippocampal
      neurons.
AB  - Activation of a purinergic P2 receptor by adenosine 5'-triphosphate (ATP) has
      previously been shown to open a non-selective cation channel with a reversal
      potential of approximately 0 mV. We examined the effect of P2 receptor activation
      on voltage-gated ionic currents in acutely isolated CA3 pyramidal neurons from
      guinea pig hippocampus using the whole-cell-patch technique. Under conditions
      designed to isolate current through voltage-dependent Ca channels (ICa), ATP (50
      microM) potentiated ICa by 36%. This increase in ICa desensitized back to control
      levels within 4 min. In contrast to the non-selective cation channel, ICa
      elicited from a holding potential (HP) of -100 mV showed significant potentiation
      in response to ATP when depolarized to a test potential (TP) of -10 mV but showed
      no effect on ICa when the same neuron was alternately depolarized to TP = -70 mV.
      No change in holding current at HP = -100 mV occurred. Tail currents were
      unaffected by ATP exposure suggesting that ICa potentiation was not due to
      modulation of L-type Ca channels. This potentiation was also observed either with
      ATP-gamma-s, the slowly hydrolyzable ATP analog, or with ATP in the presence of
      alpha, beta-methylene-ADP, an ectonucleotidase inhibitor, indicating that the
      effects observed were not due to activation of an adenosine receptor that
      required ATP hydrolysis. The potentiation of ICa was not observed with the P2X
      agonist, beta, gamma-methylene-ATP. These results suggest that ATP receptors can
      modulate voltage- as well as ligand-gated channels permeable to calcium and may
      play an important role in the dynamics of intracellular Ca2+ in these neurons.

PMID- 8739641
TI  - Selective cyclooxygenase-2 inhibition reduces carrageenan oedema and associated
      spinal c-Fos expression in the rat.
AB  - Pre-administered NS-398 (0.1, 1 and 10 mg/kg p.o.), a selective cyclooxygenase-2
      inhibitor without gastro-intestinal side-effects, dose-dependently reduced
      carrageenan evoked spinal c-Fos expression (16 +/- 4%, 32 +/- 3% and 56 +/- 5%
      reduction, respectively) at 3 h after intraplantar carrageenan. The effects of NS
      398 on carrageenan induced peripheral oedema and spinal c-Fos expression were
      correlated, thus demonstrating the beneficial relief of inflammatory pain.

PMID- 8739642
TI  - Normal development of tyrosine hydroxylase and serotonin immunoreactive fibers
      innervating anterior cingulate cortex and visual cortex in rabbits exposed
      prenatally to cocaine.
AB  - Anterior cingulate cortex develops abnormally in rabbits exposed to cocaine in
      utero but visual cortex is normal. The interactions of cocaine with the dopamine,
      norepinephrine and serotonin systems makes each a potential candidate for
      influencing these developmental effects. Here, we report no differences in the
      distribution and density of serotonin and tyrosine hydroxylase-immunoreactive
      fibers in the anterior cingulate cortex in postnatal rabbits exposed prenatally
      to cocaine or saline. Because the pattern and extent of cortical innervation by
      these systems appears normal, the data suggest that the effects of prenatal
      exposure to cocaine may involve changes in monoamine signaling distinct from
      morphological reorganization of the cortical afferents.

PMID- 8739643
TI  - Differential distribution of three types of nociceptive neurons within the caudal
      bulbar reticular formation in the cat.
AB  - Nociceptive neurons within the reticular formation (RF) caudal to the obex were
      studied. 197 units recorded from the lateral part of subnucleus reticularis
      ventralis had receptive fields in the head, 72 units recorded from the medial RF
      in the body, and 160 units recorded from the middle third of RF in the head and
      body. About half of the units tested were antidromically excited by stimulation
      of nucleus centralis lateralis.

PMID- 8739645
TI  - Quality assurance in palliative care--a growing "must"?

PMID- 8739644
TI  - Differential distribution of four types of tooth pulp neurons in the caudal
      medulla oblongata of the cat.
AB  - The medulla oblongata caudal to the obex was explored for neurons responsive to
      tooth pulp (TP) stimulation in cats. Four different classes of TP neurons were
      found. They were TP specific neurons, trigeminal wide dynamic range neurons with
      TP input, trigeminal subnucleus reticularis ventralis (SRV) neurons with TP input
      and convergent reticular formation with TP input. They were differentially
      distributed within the caudal medulla oblongata.

PMID- 8739646
TI  - Supportive care in cancer patients in St. Petersburg.
AB  - The supportive care programme in St. Petersburg has existed for more than 10
      years and works mainly with breast cancer patients. It includes physical
      procedures, psychotherapy and support given by volunteers of the Hope/ Nadezhda
      Association, who operate in accordance with the Reach to Recovery International
      Programme. In the last stages the pain relief service is activated and has good
      results. The Anticancer/Antirak Society in St. Petersburg provides cancer
      patients with help and information. Our experience with this kind of care is
      described and some outcomes are reported.

PMID- 8739647
TI  - Quality of final care for terminal cancer patients in a comprehensive cancer
      centre from the point of view of patients' families.
AB  - The aim of this study was to evaluate the quality of care for terminal cancer
      patients at our institution, as assessed by families in a questionnaire sent 6
      months after the death of the patient. We evaluated the quality of information
      given to the patients and to their families, the patients' "comfort" at the end
      of their lives (nursing, pain, psychological support) and the families' opinions
      about the practical conditions at the time of death (in our institution or at
      home). A total of 105 consecutive patients who died in our institution between
      January and June 1989 were included in the study; the vast majority had breast or
      head and neck cancers. We obtained a total of 48 answers from the 105 families
      that received the questionnaire. Of these, 87.5% were satisfied with the terminal
      nursing care, 77% were satisfied with the information given to patients and 60%
      with the information given to families. The treatment for pain was considered to
      be inefficient or incomplete by 21% of the families; 32 families (67%) considered
      that the death of terminal cancer patients should occur in the hospital where the
      patient had been treated and 12% felt that it should occur at home. This study
      led us to examine various means for improving the quality of care for our
      terminal cancer patients.

PMID- 8739648
TI  - Quality of life in patients with ovarian cancer: current state of research.
AB  - Ovarian cancer is the most malignant cancer in women, where it is the fifth
      leading cause of cancer-related death. The disease and its treatment have
      considerable effects on the quality of life of patients with this cancer. This
      study reviews existing literature on quality of life in patients with ovarian
      cancer to demonstrate the importance of the topic, to comment on improvements
      achieved and to consider their implications for the implementation of optimal
      treatment. A literature search was carried out through MEDLINE and of published
      papers on quality of life in patients with ovarian cancer from 1976 to 1994.
      Twenty papers have been reviewed, of which, 10 were treatment-related assessments
      of quality of life and the remaining 10 dealt with different topics including
      psychometric issues in measuring health-related quality of life. Twenty-four
      instruments were employed to measure quality of life. Of these, the Rotterdam
      Symptom Checklist (RSCL) and The European Organisation for Research and Treatment
      of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) were found to be the
      most appropriate. Although meta-analysis of results is impossible, it appears
      that debulking surgery followed by platinum-based chemotherapy could improve both
      quality of life and survival. In addition to effective and efficient treatment,
      psychological counselling, palliative and home care, nutritional support and pain
      relief are the most important areas for improving quality of life of patients
      with ovarian cancer. Knowledge and insight into the quality of life of patients
      with ovarian cancer are still limited, and a large carefully planned
      international study is required. Use of existing standard measures is preferable
      and agreement should be reached on a selected single instrument.

PMID- 8739649
TI  - The last 3 months of life of cancer patients: medical aspects and role of home
      care services in southern Switzerland.
AB  - The clinical data on terminal cancer patients who have died since the
      establishment of a program of collaboration between community services and the
      cancer center of Canton of Ticino, southern Switzerland, were retrospectively
      analyzed to describe the characteristics of patients seen and the effect on them
      of a home-care program coordinated by the cancer center. The home-care program is
      based on five geographically grouped community-based domiciliary services, with
      the addition of one nurse responsible for coordination and one physician from the
      oncology center. Selection criteria for participation in the home-care program
      are defined. The main outcome measures were: number of hospitalizations and
      median hospital stay during the last 3 months of life; reasons for and median
      length of last hospitalization; place of death of patients who had home care and
      those who did not. In the group of 993 patients analyzed, the median contact time
      with the cancer center was 9.5 months (10th percentile: 1 month, 90th percentile:
      71 months); the most frequent neoplasm was lung cancer (22%) with the briefest
      contact time (7.5 months; 10th percentile: 1 month; 90th percentile: 21 months);
      13.5% of patients were never hospitalized; half of the patients had a total
      hospital stay of 24 days or longer and 23% died at home. The sociodemographic and
      medical characteristics of home-care users were similar to those of the home-care
      non-users and to those of the overall group. In the group of home-care users (32%
      of the total) 22% were never hospitalized, half of the patients had a total
      hospital stay of 17 days or longer, and 43.5% of them died at home. These values
      were significantly different (P > 0.001) from those reported in the group of home
      care non-users. Palliative care, provided at home through community-based
      domiciliary services, is associated with less frequent and shorter
      hospitalizations in the last 3 months of life. Medical oncology and palliative
      treatments should be mutually complementary to improve patients care. Cancer
      centers should be involved in the planning and coordination of supportive-care
      domiciliary services.

PMID- 8739650
TI  - Concerns, coping and quality of life in head and neck cancer patients.
AB  - This study was conducted to explore the concerns and coping mechanisms used by
      patients with head and neck cancer and assess their quality of life. A group of
      50 consecutive patients with oral and laryngeal cancers were interviewed using a
      coping and concerns checklist and a semistructured interview proforma to elicit
      the common concerns in relation to head and neck cancers and their surgical
      treatment. The Hospital Anxiety and Depression Scale was used to detect anxiety
      and depression. Concerns were compared between oral and laryngeal cancers and
      between preoperative and postoperative patients. Commonest concerns were about
      the future (64%), subjective physical evaluation (60%), finances (56%), being
      upset (54%), communication (54%), current illness (52%) and inability to do
      things (50%). The commonest coping mechanisms used were helplessness and
      fatalism. Resolution was noted in less than 40% of the frequent concerns. As
      compared to laryngeal cancer patients, those with oral cancer significantly more
      often had concerns about current illness, subjective evaluation of health, eating
      and chewing, social interactions, pain and disfigurement (P < 0.05). Most
      subjects had numerous unresolved concerns. Mainly ineffective coping mechanisms
      such as helplessness and fatalism were employed leading to incomplete resolution.
      Interventions to minimise these concerns and to handle associated anxiety and
      depression would improve their quality of life.

PMID- 8739651
TI  - Psychological distress in survivors of Hodgkin's disease.
AB  - The object of this study was to reveal the psychological distress among survivors
      of Hodgkin's disease. Between 1985 and 1993, 55 patients were treated for
      Hodgkin's disease at our small oncological unit. In December 1994 all 49
      survivors were mailed a questionnaire consisting of the Impact-of-Event Scale and
      a visual-analogue scale measuring quality of life, to which 42 patients responded
      (86%). Half of the patients reported moderate to high levels of psychological
      distress. Scores predicting significant stress response syndrome were revealed in
      19% of the patients. Women reported statistically significant lower psychological
      distress on the intrusion (P = 0.025) and avoidance scale (P = 0.047) and a
      higher quality of life (P = 0.032). In order to improve patients' care and
      support, cases at risk should be identified. Among patients with Hodgkin's
      disease, men seems to be at highest risk. This study should be helpful for
      developing supportive interventions for survivors of Hodgkin's disease.

PMID- 8739652
TI  - Helping children cope when a family member has cancer.
AB  - A cancer diagnosis impacts the entire family unit, but children are especially
      vulnerable. In the past, families and professionals did not share information or
      allow for children to express their feelings or to be involved. Children have the
      right to know and the need to know the truth. Interventions should be based on
      both the developmental stage of the child and the stage of the illness.
      Approaches by disease phase and developmental stage are discussed. Goals include
      maintaining family stability, preparing children for what may happen, allowing
      for flexible communication, and preventing serious psychosocial sequelae.

PMID- 8739654
TI  - Initial empirical antibiotic therapy for neutropenic fever: analysis of the
      causes of death.
AB  - We have reviewed the records of all patients who were included in EORTC-IATCG
      protocols for the empirical treatment of febrile neutropenia at the Institut
      Jules Bordet from 1984 to 1994. Of the 410 granulocytopenic patients, 49 died
      during or after febrile neutropenia. Among these, 19 died from infection, 18 from
      progressive neoplasia, and 12 from other causes. Fatal bacterial infection
      occurred in 10 patients and arose during the first 10 days; fatal fungal
      infection occurred in 7 patients, all of whom had a profound and protracted
      granulocytopenia (polymorphoneutrophil count < 100/mm3 for more than 20 days). In
      comparison with a previous similar study (1974-1983) our present observations
      shows a decrease of overall mortality during or after febrile neutropenia and an
      increase of gram-positive microorganisms and fungal pathogens as a cause for
      infectious deaths.

PMID- 8739653
TI  - Prevention of infection in children with acute leukaemia. No major difference
      between total and selective bowel decontamination.
AB  - To evaluate the effect of total bowel decontamination (TD) and selective bowel
      decontamination (SD) in a non-protective environment clinical and laboratory data
      of children treated for acute leukaemia between 1983 and 1991 were analysed
      retrospectively. From 1983 until 1989 34 patients [18 acute non-lymphoblastic
      leukaemia (ANLL) patients, 16 acute lymphoblastic leukaemia (ALL) patients]
      received TD and 31 patients (8 ANLL patients, 23 ALL patients) received SD from
      1987 until 1991. TD consisted of colistin sulphate, neomycin, cephaloridine and
      amphotericin B orally as well as Orabase and sterilized food, while the patients
      were nursed in a single room. SD consisted of oral colistin sulphate, neomycin
      and amphotericin B. Those patients with ANLL were nursed in a single room;
      patients with ALL were nursed in a single room during remission induction therapy
      only. All patients except those with ANLL receiving TD received Pneumocystis
      carinii pneumonia prophylaxis with cotrimoxazole. Because the two groups were
      heterogeneous for diagnosis and chemotherapy the occurrence of fever (central
      body temperature at least 38.5 degrees C) and major infections (septicaemia of
      infections of the deep tissues or organs) were registered during periods of
      neutropenia (neutrophilic granulocytes < or = 500/mm3 for at least 8 days).
      Patients on TD had 55 periods of neutropenia, patients on SD 80. Patients on TD
      had 89.1 periods of fever/100 periods of neutropenia whereas patients on SD had
      56.3. Also patients on TD had 27.3 major infections/100 periods of neutropenia
      whereas patients on SD had 11.3. Major infections predominantly consisted of
      septicaemia caused by gram-positive bacteria. We conclude that, in this study, TD
      in a non-protective environment does not offer better protection against major
      infections that SD in patients with ALL or ANLL.

PMID- 8739655
TI  - The role of bisphosphonates in the treatment of bone metastases--the U.S.
      experience.
AB  - Frequent complications of bone metastases include pain, pathologic fracture,
      hypercalcemia and spinal cord compression. Lytic bone metastases result from
      excessive activation of osteoclasts by tumor-produced cytokines. Aredia
      (pamidronate) is a potent bisphosphonate that inhibits osteoclast activation. In
      two dose-seeking phase I trials in patients with breast cancer and prostate
      cancer, repeated intravenous infusion of Aredia was shown to be safe and
      effective in reducing bone resorption and pain. In a randomized phase III trial
      of 377 patients with multiple myeloma, Aredia was administered in a dosage of 90
      mg i.v. every 4 weeks. Compared with placebo, treatment with Aredia was
      associated with a significant decrease in bone pain and in the incidence and time
      to development of all skeleton-related events. Data from two phase III breast
      cancer trials each involving 300 patients are now being analyzed. The newer
      bisphosphonates can safely be used together with standard anticancer therapy to
      provide effective palliation of symptoms caused by lytic bone metastases.

PMID- 8739656
TI  - Cisplatin-associated anaemia in patients with solid tumours. A retrospective
      evaluation and considerations relative to erythropoietin administration.
AB  - We have reviewed the incidence of cisplatin-induced anaemia in patients affected
      with solid tumours treated with at least three courses of first-line cisplatin
      containing regimens. In our experience, a low percentage (5%) of patients
      required transfusions of red blood cells. We think it is of the utmost importance
      to adopt uniform criteria in monitoring and treatment of patients at risk of
      developing cisplatin anaemia and to identify subsets of patients to eventually
      treat with erythropoietin.

PMID- 8739657
TI  - A 5-year follow-up study of suicide attempts.
AB  - Seventy-five patients were admitted to the ward of the Lund Suicide Research
      Center following a suicide attempt. After 5 years, the patients were followed up
      by a personal semistructured interview covering sociodemographic, psychosocial
      and psychiatric areas. Ten patients (13%) had committed suicide during the follow
      up period, the majority within 2 years. They tended to be older at the index
      attempt admission, and most of them had a mood disorder in comparison with the
      others. Two patients had died from somatic diseases. Forty-two patients were
      interviewed, of whom 17 (40%) had reattempted during the follow-up period, most
      of them within 3 years. Predictors for reattempt were young age, personality
      disorder, parents having received treatment for psychiatric disorder, and a poor
      social network. At the index attempt, none of the reattempters had diagnoses of
      adjustment disorders or anxiety disorders. At follow-up, reattempters had more
      psychiatric symptoms (SCL-90), and their overall functioning (GAF) was poor
      compared to those who did not reattempt. All of the reattempters had long-lasting
      treatment ( > 3 years) as compared to 56% of the others. It is of great clinical
      importance to focus on treatment strategies for the vulnerable subgroup of self
      destructive reattempters.

PMID- 8739658
TI  - Paroxetine and amitriptyline in the treatment of depression in general practice.
AB  - A total of 144 outpatients in general practice in Denmark, aged 18-65 years and
      diagnosed as suffering from depression with a HAMD-17 score of 15 or more, were
      included in this 8-week double-blind, randomised, multicentre, controlled,
      parallel group comparison of paroxetine versus amitriptyline. The purpose of the
      study was primarily to evaluate efficacy and tolerance of treatment. In addition,
      focus was added on weight change and subjective well-being. The efficacy results
      showed equal effect of both drugs. However, paroxetine was tolerated better than
      amitriptyline, and this difference reached the level of significance when four
      non-evaluable patients were taken out of the analysis. Moreover, there was a
      significant weight increase in the amitriptyline group and no significant weight
      change in the paroxetine group. There was no difference between the groups as
      regards subjective well-being as measured by the VAS. In conclusion, paroxetine
      is an effective and well-tolerated antidepressant, and well-suited for the
      treatment of depression in general practice.

PMID- 8739659
TI  - Effect of pharmacotherapy on serum cholesterol levels in patients with panic
      disorder.
AB  - It is unclear whether elevated cholesterol level is a complication of panic
      disorder (PD) or is associated with pharmacotherapy. We compared the total
      cholesterol (TC) level in 47 PD patients with that in 47 gender- and age-matched
      normal controls (NC), and we also examined the pre- and post-treatment TC levels.
      There was no sex difference in TC. Before pharmacotherapy, the mean TC level in
      the PD group (194.9 +/- 39.6 mg/dl) was non-significantly higher than that in the
      NC group (190.5 +/- 26.7 mg/dl). The mean TC level in the PD group was
      significantly reduced following the pharmacotherapy (post-TC: 184.7 +/- 31.0
      mg/dl; t = 2.44, P < 0.02), and the subgroup treated with alprazolam (n = 26)
      showed markedly significant decrease of TC after the treatment (t = 2.36, P <
      0.03). The TC level in the PD subgroup with agoraphobia (n = 24, 198.9 +/- 37.9
      mg/dl) was slightly higher than that in the group without agoraphobia (n = 23,
      190.8 +/- 41.6 mg/dl). These findings suggest that there is a relationship
      between cholesterol levels and treatment in PD.

PMID- 8739660
TI  - An analysis of age and gender influences on the relative risk for suicide and
      psychotropic drug self-poisoning.
AB  - Psychiatric illness is a significant risk factor for both attempted and completed
      suicide and psychotropic medications account for 80% of all drug overdoses
      involving prescription medications. One challenge facing clinicians is to balance
      the benefit of treatment against the risk of drug overdose. The aim of the
      present study was to compare the age and gender distribution of patients
      prescribed psychotropic drugs with patients attempting and completing suicide
      with these drugs. Data were obtained from the Australian census and studies of
      general practitioner prescribing, patients who committed suicide or presented
      with self-poisoning within a defined geographic area. The characteristics of
      these populations were compared to calculate odds ratios for attempting or
      completing suicide with psychotropic drugs, before and after correction for rates
      of prescription, in different age and gender groups. The odds ratios (ORs) for
      self-poisoning were higher for those aged less than 45 years and yet this group
      was least likely to be prescribed psychotropic drugs. Men had a much higher rate
      of completed suicide using more lethal methods. The ORs for self-poisoning and
      suicide with psychotropic drugs, after correction for prescription rates, for
      those aged 15 to 24 years were 11.1 and 1.7, respectively. Those aged 25 to 44
      years had ORs of 4.9 and 4.3, and, by contrast, those over 75 years had ORs of
      0.03 and 0. Women were slightly more likely to poison themselves with
      psychotropic drugs (OR 1.2). However, the situation reversed after correction for
      prescription rates (OR 0.69). It is concluded that greater caution should be
      exercised in prescribing for those under 45 years of age, given their relatively
      higher risk of drug overdose, and that the least toxic compounds should be used.
      The risk (of self-poisoning) among the elderly may have been overstated, so that
      some patients may have been denied the benefit of adequate treatment.

PMID- 8739661
TI  - Avoidant personality disorder and taijin kyoufu: sociocultural implications of
      the WHO/ADAMHA International Study of Personality Disorders in Japan.
AB  - This paper discusses the characteristics of avoidant personality disorder in a
      cultural context based on the Japanese concept of taijin kyoufu as well as that
      of DSM-III-R and DSM-IV social phobia. Sixty-six patients were given the
      International Personality Disorder Examination and questionnaires including the
      Beck Anxiety Inventory. Among the 23 DSM-III-R personality disorder patients, 8
      patients were diagnosed as having avoidant personality disorder. Six of them were
      suffering from taijin kyoufu symptoms. Among 27 ICD personality disorder
      patients, 22 patients were diagnosed as having ICD anxious personality disorder.
      All DSM avoidant patients were included in the ICD anxious group. These findings
      suggest that patients with avoidant personality disorder have had a long history
      of difficulties and share common personality problems with a milder form of
      taijin kyoufu, which is conceptually different from social phobia.

PMID- 8739662
TI  - What do anxiety scales measure?
AB  - At present researchers appear to rely on instruments for the assessment of
      anxiety without due consideration of what it is that the instrument may be
      presumed to measure. A survey was undertaken of the presently most frequently
      used rating scales which purport to assess anxiety. The allocation of items of
      the scales to the major aspects of anxiety was examined. It was found that the
      scales tapped different areas of psychopathology. Furtherance of research
      requires closer attention to the nature of the scales and the assumption that
      they all measure much the same construct must be discarded.

PMID- 8739663
TI  - A naturalistic 6-year follow-up study of patients with panic disorder.
AB  - A clinical sample of 55 patients meeting the diagnostic criteria for panic
      disorder (PD) were enrolled in this long-term study. The patients were treated
      initially with alprazolam or imipramine during a period of 9 weeks. A clinical
      psychiatric examination was carried out at the beginning and at the end of the
      initial treatment period and 3 and 6 years after the enrollment. Although most of
      the patients (74%) had no panic attacks at the end of the 6-year follow-up
      period, 9 (18%) had major depression and 6 (11%) severe suicidality. Seven of
      these depressive patients also suffered from alcoholism. Sixty per cent of the
      patients were still on medication at the end of the follow-up. Depression,
      suicidality and alcoholism seem to be the long-term consequences of PD.

PMID- 8739664
TI  - A double-blind multicentre comparison of mirtazapine and amitriptyline in elderly
      depressed patients.
AB  - A total of 115 elderly patients (60-85 years of age) with DSM III diagnosis of
      major depressive episode were randomly assigned to 6 weeks of treatment with
      either mirtazapine, 15-45 mg/day, or amitriptyline, 30-90 mg/day. Efficacy was
      assessed biweekly, using the Hamilton Rating Scale for Depression (HRSD) and
      Montgomery and Asberg Depression Rating Scale (MADRS) as primary outcome
      variables. The treatment with both drugs resulted in a similar reduction of total
      HRDS and MADRS scores, with no statistically significant differences between
      treatment groups at any assessment point or at endpoint. Statistically
      significant differences favouring amitriptyline were present according to CGI
      Global Improvement Scale at endpoint, HRDS cognitive disturbance factor at weeks
      2, 4 and 6 and endpoint and retardation factor at week 6. Adverse events were
      reported by a similar number of patients in both treatment groups. Additional
      research is needed to assess further the efficacy and tolerability of mirtazapine
      among elderly depressed patients.

PMID- 8739665
TI  - The sleep of non-depressed patients with panic disorder: a comparison with normal
      controls.
AB  - All-night sleep EEG recordings were performed in non-depressed patients with
      panic disorder, agoraphobia, and a group of age- and sex-matched normal controls.
      Patients were selected according to DSM-IV and all subjects were studied under
      drug-free conditions. In addition to sleep continuity disturbances, patients with
      panic disorder have a reduced percentage of slow wave sleep, mainly due to
      diminished amounts of stage 4. REM sleep characteristics are identical in the two
      groups. When depressive co-morbidity and non-specific causes of insomnia are
      excluded, the sleep EEG of panic patients seems to be characterized by modest
      changes in sleep continuity and sleep architecture. These findings favour the
      existence of a neurophysiological frontier between anxiety disorders and
      depressive illness.

PMID- 8739666
TI  - Alexithymia in suicide attempters.
AB  - Alexithymia seems to share some common features with psychological constriction,
      a phenomenon described in suicidal individuals. Fifty suicide attempters were
      interviewed within 24 h after arrival at a hospital, and measures of lethality of
      the attempt, suicidal intent, depression and alexithymia were carried out with
      structured instruments. Almost all the attempters were depressive, and about half
      of them were also alexithymic. However, alexithymia was not more prevalent in
      this population than in non-suicidal depressive patients. Depression and
      alexithymia correlated significantly with each other, but there was no
      correlation between alexithymia and lethality of the suicide attempt or suicidal
      intent. The authors conclude that alexithymia in suicide attempters seems to be
      associated with depression, but not with suicidality per se. Therefore,
      measurement of alexithymia may not yield extra information in suicide risk
      assessment.

PMID- 8739667
TI  - Relatives' beliefs about the causes of schizophrenia.
AB  - Based on a representative survey among the members of German and Austrian
      associations of relatives of mentally ill people, this paper examines the beliefs
      commonly held by relatives of persons suffering from schizophrenia concerning the
      causes of this disorder. A comparison of the information gathered in the course
      of this survey with the results of a representative survey conducted among the
      general public in Germany shows that relatives will usually look to biological
      factors when searching for the cause of schizophrenia, while the general public
      tends to cite psychosocial factors, especially stress-related factors, in order
      to explain the development of this illness. We attribute this discrepancy to
      relatives' greater exposure to the knowledge of psychiatric experts as well as
      their having to deal with their own feelings of guilt.

PMID- 8739668
TI  - Long-term effects of transference interpretations: comparing results from a quasi
      experimental and a naturalistic long-term follow-up study of brief dynamic
      psychotherapy.
AB  - A follow-up study, using a quasi-experimental non-equivalent groups comparison
      design, the so-called regression discontinuity design, reported a negative long
      term effect of a high frequency of transference interpretations given to patients
      in brief dynamic psychotherapy who had been deemed highly suitable for such
      treatment. The major threat to internal validity of the findings was the
      possibility that the patients who were evaluated as highly suitable for dynamic
      psychotherapy might be the ones with the naturally worst outcomes, independent of
      therapy technique (selection maturation). Data from a similar naturalistic study
      with no quasi-experimental manipulation of the treatment technique revealed,
      however, that highly suitable and relatively less suitable patients had similar
      outcomes. This makes selection maturation a less plausible confound of the
      (negative) treatment effect estimated in the quasiexperimental study. A high
      frequency of transference interpretations in brief dynamic psychotherapy seems to
      be causally related to less favourable long-term dynamic change.

PMID- 8739669
TI  - GHQ-28 as an aid to detect mental disorders in neurological inpatients.
AB  - The prevalence of mental disorders (DSM-IIIR criteria) among 107 neurological
      inpatients was estimated, as well as the extent to which disorders were detected
      by neurologists. The validity of the scaled version of the General Health
      Questionnaire (GHQ-28) was evaluated using Receiver Operating Characteristic
      (ROC) analysis and DSM-IIIR as external criteria. Of the 107 patients who
      submitted to a structured psychiatric interview (SCID-R), 56 (52.3%) showed
      evidence of a mental disorder. Major depressive episode (n = 16), generalized
      anxiety disorders (n = 13) and dysthymia (n = 12) were the most frequent
      diagnoses. The neurologists recognized only 13/107 cases (12.1%). Significantly
      more women than men exhibited some form of mental disorder. The validation of GHQ
      28 in the series of 107 neurological inpatients indicated that the best trade-off
      between sensitivity and specificity was the cut-off score of 5/6. The high
      occurrence of mental disorder, in association with the low rate of detection by
      the neurologists, points to the need for special attention to be paid to this
      problem by staff and experts.

PMID- 8739670
TI  - Ketoacidosis as a side-effect of clozapine: a case report.

PMID- 8739671
TI  - Ear disease and schizophrenia: confounding factors.

PMID- 8739672
TI  - Prevalence of open-angle glaucoma in central Sweden. The Tierp Glaucoma Survey.
AB  - A population-based survey of 760 people 65-74 years of age was conducted in the
      municipality of Tierp, central Sweden. The methods used to identify glaucoma
      suspects were applanation tonometry, automatic perimetry (Competer 350), and
      binocular assessment of the optic disc. For a diagnosis of definite open-angle
      glaucoma, a visual field defect was required. Open-angle glaucoma was found at a
      prevalence of 5.70% (95% confidence interval: 4.12-7.27), which is higher than
      those figures reported for comparable surveys carried out on white populations.
      The occurrence of capsular glaucoma may in part explain this finding. Twenty of
      the 45 open-angle glaucomas were diagnosed before the survey. In this category,
      capsular glaucoma accounted for 60%, whereas 84% of cases detected during the
      survey were chronic simple glaucomas. Eight cases (18%) were classified as normal
      tension glaucoma, all of whom were diagnosed during the survey. Chronic simple
      glaucoma was significantly more prevalent in males than in females.

PMID- 8739674
TI  - Sensitivity and specificity of structural optic disc parameters in chronic
      glaucoma.
AB  - We studied different structural optic disc parameters and their ability to
      discriminate between normal and glaucoma eyes using computerized raster
      tomography. Two hundred and seventy-six eyes of 138 normal subjects and 146 eyes
      of 102 glaucoma patients were examined with a raster tomographic imaging system
      (The Glaucoma-ScopeTM, Ophthalmic Imaging Systems, Sacramento, CA). Glaucoma eyes
      were classified into four groups according to their perimetric mean deviation
      values. Minimum rim width within the 60 degrees and 90 degrees sectors across the
      vertical meridian, vertical and horizontal cup-disc ratio, rim and cup area were
      calculated for each optic disc. Receiver operating characteristics curves were
      set up for comparisons of the different parameters. Representing localised
      changes of the optic disc, minimum rim width 60 degrees and 90 degrees showed the
      best separating characteristics with sensitivity values of 91% at a fixed
      specificity of 90%, followed by vertical cup-disc ratio. Global indices like cup
      and rim area and horizontal cup-disc ratio showed the poorest separation. These
      differences were particularly obvious in the group with mild to moderate
      glaucomatous visual field defects. Thus, global parameters were less likely to
      detect early focal glaucomatous optic nerve head changes, than parameters
      representing localised changes.

PMID- 8739673
TI  - Screening techniques for angle-closure glaucoma in rural Taiwan.
AB  - 562 residents of Jin Shan aged 40 years and above underwent examinations to
      compare the sensitivity and specificity of oblique flashlight, peripheral slit
      beam and ultrasonographic evaluation of the anterior chamber depth to gonioscopy
      in detecting cases of PACG. Among 5441 eligible individuals aged 40 and above,
      562 (10.3%) underwent screening for PACG, of whom 17 (3.02%) were defined as
      cases, and 10 (1.78%) as suspects. Home visits indicated that respondents for
      screening were similar to the population as a whole. Only 35% of PACG cases
      reported symptoms consistent with acute angle closure, and only 18% were
      previously diagnosed. When compared to gonioscopy, only ultrasonographic
      measurement of AC depth provided an adequate mix of sensitivity and specificity.
      Ultrasonography in combination with tonometry provided a sensitivity of 88% with
      a specificity of 92%. Sensitivity and specificity for ultrasonography in
      combination with refractive status were 84% and 83% respectively. Shallower AC
      depth (p = 0.0001), shorter axial globe length (p = 0.001), greater than 2D of
      hyperopia (p < 0.001), high grades of nuclear sclerotic cataract (p < 0.0001) and
      an increased cup-to-disc ratio (p = 0.002) were significantly correlated with a
      diagnosis of PACG.

PMID- 8739675
TI  - Argon and low energy, pulsed Nd:YAG laser trabeculoplasty. A prospective,
      comparative clinical and morphological study.
AB  - Argon laser trabeculoplasty (ALT; 1.0 W, 0.1 sec, 50 microns) was performed in
      right eyes, and low energy, Q-switched Nd:YAG laser trabeculoplasty (Nd:YAGLT;
      1.1-4.8 mJ/pulse) in left eyes of 14 patients with primary open-angle glaucoma
      and in one patient with juvenile glaucoma. The pre-laser intraocular pressure
      (IOP) was medically uncontrollable (IOP > 21 mmHg). The interocular pressure
      difference varied between 0 and 3 mmHg. In 9 patients IOP decreased to less than
      22 mmHg (success) in both eyes. No statistically significant difference has been
      revealed with paired t-test in the degree of IOP decrease between ALT and
      Nd:YAGLT treated eyes during the 1-18 months' follow-up. Treatment variables of
      Nd:YAGLT had no statistically significant effect on the duration of the post
      laser success with Cox-regression. In 4 patients both treatments were ineffective
      (IOP > 21 mmHg). In 2 patients ALT was successful but Nd:YAGLT was ineffective.
      In three cases of early bilateral laser failure (IOP > 21 mmHg at the first month
      visit) trabeculectomy was performed on both eyes in the third post-laser month.
      Following ALT the uveoscleral meshwork was severely destroyed in the area of the
      laser spots, and the surrounding collagen fibres were heat-damaged. The meshwork
      between the laser spots was covered by a membrane formed by migrating endothelial
      cells. In the uveoscleral meshwork Nd:YAGLT induced severe focal damage
      surrounded by circumscript shrinkage and scarring. The juxtacanalicular tissue
      remained free of laser induced damage. No endothelial membrane was present. The
      results suggest that low energy, Q-switched Nd:YAGLT may represent an alternative
      method of glaucoma laser surgery.

PMID- 8739676
TI  - Day-case trabeculectomies: safety and efficacy.
AB  - A comparison of 90 day-case and 102 in-patient trabeculectomies is presented.
      There was no statistically significant difference in the incidence of post
      operative hyphaema (Chi-squared test p = 0.84), shallow anterior chamber (p =
      0.46), flat bleb (p = 0.84) or hypotony (p = 0.87) between the two groups.
      Casualty attendances, readmissions and further surgery in the postoperative
      period were seen with similar frequency in each group. Intraocular pressure
      control three months following surgery was not compromised by undergoing the
      procedure as a day-case (p = 0.29). This study demonstrates the safety and
      efficacy of ambulatory filtration surgery.

PMID- 8739677
TI  - Scanning Laser Ophthalmoscope microperimetry compared with Octopus perimetry in
      normal subjects.
AB  - Simultaneously performed ophthalmoscopy and perimetry by microperimetry using the
      Scanning Laser Ophthalmoscope eliminates some of the classical problems involved
      in transformation techniques in perimetry such as: optical distortions, unsteady
      fixation and alignment. Almost all reports published on microperimetry have
      addressed chorioretinal diseases, with only a few patients in each study. No
      reports have studied the normal values of this method. To evaluate the
      reliability of microperimetry, 30 healthy subjects-10 subjects from each of the
      age group: 40-49 years (male/female ratio: 4/6), 50-59 years (m/f ratio: 5/5) and
      60-69 years (m/f ratio: 5/5)-were repeatedly examined with microperimetry and
      automatic perimetry performed by the Octopus macular program M1. The results of
      the present study of microperimetry show that the standard deviation of the
      interindividual variance component was 1.36, that the standard deviation of the
      intraindividual variance component was 0.94 and that a test result obtained by
      microperimetry in any of the two locations studied can be related to a test
      result obtained by Octopus M1 in the same location.

PMID- 8739678
TI  - A 6-month, randomized, double-masked comparison of latanoprost with timolol in
      patients with open angle glaucoma or ocular hypertension.
AB  - The intraocular pressure reducing effect and side-effects of latanoprost, a
      phenyl-substituted prostaglandin analogue, were compared with those of timolol,
      in a group of 31 glaucomatous or ocular hypertensive patients, divided into three
      subgroups. The study was randomized and double masked. At the end of 6 month's
      treatment with latanoprost 0.005% once daily, either as a morning dose or as an
      evening dose, there was a reduction in intraocular pressure of 33% (p < 0.001)
      and 36% (p < 0.001), respectively. The intraocular pressure reduction of timolol
      0.5%, administered twice daily was 26% (p < 0.001). There was no significant
      difference in conjunctival hyperemia between the groups and there were few
      subjective symptoms in any of the patients. One patient with a light green-brown
      iris, treated with latanoprost in one eye only, exhibited an increase in iris
      colour in the treated eye at week 26, and did not show any signs of reversion 9
      months after discontinuing the therapy. It may be concluded that latanoprost is
      well tolerated and at least as effective as timolol in reducing intraocular
      pressure in patients with glaucoma or ocular hypertension when applied once
      daily. The exact mechanism behind the increase in iris pigmentation and the
      clinical significance of this previously unknown side-effect needs to be
      investigated further.

PMID- 8739679
TI  - Prognostic factors in long-term intraocular pressure control following combined
      phacoemulsification and trabeculectomy.
AB  - We studied 36 consecutive patients who underwent combined phacoemulsification and
      trabeculectomy to determine prognostic factors associated with intraocular
      pressure control one year postoperatively. In patients who were either easier
      (intraocular pressure < 16 mmHg, n = 19) or more difficult (> or = 16 mmHg, n =
      17) to control, the mean intraocular pressure increased up to the fourth week
      postoperatively. In the more difficult to control group, however, the intraocular
      pressure continued to increase and a statistical difference between groups was
      noted by the second month postoperatively (P < 0.05). The peak intraocular
      pressure within the first month postoperatively was lower in patients easier to
      control long-term (P < 0.005). No statistical difference between groups in the
      filtering bleb or anterior chamber appearance, or postoperative complications,
      was noted (P > 0.05). This study suggests combined trabeculectomy and
      phacoemulsification is safe and effective in controlling intraocular pressure
      postoperatively. Determining from the early postoperative examination the long
      term pressure control, however, is difficult.

PMID- 8739680
TI  - Effect of topical apraclonidine on flow properties of central retinal and
      ophthalmic arteries.
AB  - To investigate the acute effects of topically administered 1% apraclonidine
      hydrochloride on blood velocity and resistance parameters of central retinal and
      ophthalmic arteries, the vessels were studied by color Doppler ultrasonography
      during baseline and at the time of peak effect of apraclonidine in 20 healthy
      volunteers. After medication, significant decrease in peak systolic, peak
      diastolic, mean flow velocities and increase in resistive and pulsatility indices
      of ophthalmic artery were observed. Blood velocity and resistance parameters of
      central retinal artery didn't change significantly. In conclusion, topically used
      apraclonidine was thought to change the blood velocity and resistance parameters
      of ophthalmic artery as a result of its local vasoconstrictory effect on the
      anterior segment branches of ophthalmic artery.

PMID- 8739681
TI  - Possible role of transferrin in exfoliation syndrome.
AB  - Protein concentration was measured in 30 exfoliation syndrome samples and 22 age
      matched controls. Exfoliation samples contained significantly more protein than
      controls. We also analyzed by SDS gel electrophoresis 32 aqueous samples, 12 with
      exfoliation syndrome and 20 age matched controls. A novel finding in all samples
      was a double band with 77 kDa and 78 kDa. These bands probably represent
      transferrin isoforms, with different carbohydrate side chains. Exfoliation
      samples contained a lower amount of the 77 kDa band in comparison to the amount
      of the 78 kDa band. The lower relative concentration of this transferrin isoform
      in the exfoliation syndrome samples may be indicative of its possible involvement
      in the disorder. A different oligosaccharide side chain in combination with a
      relatively high protein concentration may lead to sedimentation of this molecule.
      On the other hand, laminin, a glycoprotein detected previously in exfoliation
      material, contains similar oligosaccharide side chains with transferrin. Thus the
      oligosaccharide side chains of both proteins may be influenced by the same
      factors.

PMID- 8739682
TI  - The intraocular pressure lowering effect of timolol in gel-forming solution.
AB  - The effect on the intraocular pressure (IOP) of 0.5% timolol solution given twice
      daily was compared to 0.5% timolol in gel-forming solution given once daily.
      Patients (n = 223) having an IOP of above 22 mmHg were recruited from 16 eye
      specialist centres in Scandinavia and Finland. The patients were randomized to
      two treatment groups, timolol solution treatment and timolol in gel-forming
      solution treatment. Eyes with and without pseudoexfoliation were included. The
      patients were stratified regarding the presence or not of pseudoexfoliation, to
      ensure appropriate distribution of this condition. No difference in intraocular
      pressure reducing effect was registered for the two groups. The pressure reducing
      effect of the two modes of treatment was not affected by the presence or not of
      pseudoexfoliation. The study also included registration of local and systemic
      signs and symptoms possibly related to the study medications. Blurring of vision
      occurred more often in patients given 0.5% timolol in gel-forming solution
      compared to timolol solution. The heart rate decreased statistically
      significantly in patients given timolol solution, but not in patients given
      timolol in gel-forming solution. This study suggests that treatment with 0.5%
      timolol in gel-forming solution once a day may be equally as good as 0.5% timolol
      solution given twice a day in patients with glaucoma both with and without
      pseudoexfoliation.

PMID- 8739683
TI  - Trabeculectomy in the second eye.
AB  - Trabeculectomy has a reported success rate of between 67-94%. Many studies have
      been performed on operative variables which may influence surgical outcome.
      Youth, pigmented race and anterior segment inflammation have been shown to be
      associated with trabeculectomy failure. Little is known of the surgical outcome
      of trabeculectomy in one eye in relation to its partner, when surgery is
      standardized and the above known adverse conditions to trabeculectomy success are
      absent. We therefore carried out a prospective study on 62 patients who underwent
      bilateral trabeculectomies. There was a significant failure rate amongst pairs of
      eyes (postoperative intraocular pressure > or = 21 mmHg), with the majority of
      failures occurring within 6 months of surgery. Failure appeared to be associated
      with a longer period from diagnosis of glaucoma to surgery, and the use of a
      wider variety and number of topical medications. All other trabeculectomy
      complications occurred more commonly in any single eye, than in any pairs of
      eyes.

PMID- 8739684
TI  - The importance of early diagnosis of treatable diabetic retinopathy for the four
      year visual outcome in older-onset diabetes mellitus.
AB  - The four-year visual outcome was retrospectively studied in patients with older
      onset diabetes mellitus and diabetic retinopathy in need of laser treatment.
      Visual acuity in 53 patients examined by ophthalmologists who referred the
      patients for an evaluation of retinopathy before laser treatment, was compared to
      that of 47 patients examined by ophthalmologists who also performed the
      photocoagulation. The number of eyes that became blind (visual acuity < or =
      6/60) during the four-year period was higher (23/90 vs 9/91; p < 0.01) among
      referred patients, whereas the number of retinal examinations per patient during
      the three-year period prior to laser treatment did not differ between the two
      groups. Among referred patients, 13% had not been ophthalmologically examined
      before the treatment-requiring retinopathy was found. Corresponding figure for
      those examined at the laser centre was 23%. Severe macular oedema in regularly
      examined patients was more common among referred patients (9/30 vs 1/32; p <
      0.01). The results indicate that screening for diabetic retinopathy in older
      onset diabetes was not performed satisfactorily. In addition, laser treatment was
      delayed in older-onset diabetic patients controlled by ophthalmologists who
      referred patients for photocoagulation, resulting in an increased incidence of
      legally blind eyes. The study also stresses the importance of carrying out
      knowledge of when and how to diagnose early sight-threatening diabetic
      retinopathy to ophthalmologists referring patients for laser treatment.

PMID- 8739685
TI  - Spatial tuning loss of pattern reversal visual evoked response in optic nerve
      disease.
AB  - We compared the pattern reversal visual evoked response (PVER) amplitude-check
      size functions from 25 eyes (25 normal subjects; visual acuities > or = 20/20)
      with those from 32 eyes (22 patients; visual acuities 20/15 to 20/50; mean,
      20/25.5) with mild optic nerve disease to determine if spatial tuning loss of the
      PVER occurs in the presence of optic nerve dysfunction. The steady-state PVER was
      recorded with five check sizes (range, 160 to 10 minutes of arc). To analyze the
      PVER amplitude-check size function, we calculated the difference between the
      maximum and minimum PVER amplitudes and then calculated the area of spatial
      tuning (the area under the function). Values were significantly smaller in
      patients than in normal subjects (1.81 +/- 1.27 microV versus 5.73 +/- 3.27
      microV; F = 41.24, p = 0.0001; 3.87 +/- 2.70 area units versus 12.57 +/- 7.60
      area units; F = 38.62, p = 0.0001). There was no shift in the distribution of
      peak check sizes. Results suggest that a spatial tuning loss occurs in optic
      nerve disease. The shape of the function, including the area of spatial tuning,
      appears to be a sensitive indicator of early or mild optic nerve dysfunction.

PMID- 8739686
TI  - Macula study with standardized echography.
AB  - At an early clinical stage, patients with cystoid macular oedema show no
      significant changes in their vision. This phase is described as angiographic
      cystoid macular oedema. Echographic macular studies have in the past years shown
      that the macular thickness is increased in the early stages of cystoid macular
      oedema. In these patients there was no evidence of cystoid macular oedema with
      the visual acuity test, B-scan echography and fluorescein angiography. In this
      paper an echographic macular study by standardized A-scan echography was
      performed in 537 patients before extracapsular cataract extraction and
      intraocular lens implantation in posterior chamber (ciliary sulcus). The results
      showed that this method is very sensitive in detecting patients with high risk of
      cystoid macular oedema.

PMID- 8739687
TI  - Investigation of microbial keratitis: an audit from 1988-1992.
AB  - An audit was performed of the investigation of 263 cases of microbial keratitis
      severe enough to be admitted to the Manchester Royal Eye Hospital over the 5-year
      period, 1988-1992. A pathogen isolation rate of 37% was noted during the first
      year which increased to 79% (p < 0.05) by the final year of audit. In late 1991 a
      new method of inoculating enrichment broths was introduced, which also
      contributed by increasing the yield from corneal scrapes. The audit process
      resulted in the development of and adherence to our investigation protocol,
      improved communication between Manchester Royal Eye Hospital and the microbiology
      laboratory, the implementation of a new investigatory method, and a significantly
      improved microbial isolation rate.

PMID- 8739688
TI  - The results of penetrating keratoplasty for keratoconus.
AB  - At the Department of Ophthalmology, University Hospital in Lund, Sweden,
      keratoconus is the most common indication for penetrating keratoplasty. We
      studied 77 keratoplasties performed on keratoconic eyes between 1989-1991.
      Postoperative corrected visual acuity was better than or equal to 0.5 in 65 eyes
      (84.4%), and 30 eyes (39%) had visual acuity of 1.0. The mean postoperative
      astigmatism was 3.75 D with a range of 0-12.5 D. Eight patients underwent
      relaxing incision with satisfactory results in 6 patients. Graft rejection was
      observed in 6 eyes (7.8%). The most serious complication seen in our group of
      patients was a retrocorneal fibrous membrane that developed in one patient.

PMID- 8739689
TI  - Idiopathic orbital inflammatory disease.
AB  - The purpose of this study was to review our clinical experience with 132
      idiopathic orbital inflammation cases seen between 1971 and 1994. Clinical charts
      of the patients were evaluated retrospectively. Patient age ranged from 5 to 80
      (mean 46.5) years. The follow-up period was between 6 to 172 (mean 42.8) months.
      Proptosis (82%), motility restriction (54%), visual acuity loss (38%) were the
      three more common presenting signs. The diagnosis was made by open biopsy in 96
      cases and clinically in 36 cases. Radiologic patterns of involvement were
      available for 84 cases. Diffuse inflammatory disease (40 cases) was the most
      frequent radiologic pattern followed by myositis (21 cases) and dacryoadenitis
      (14 cases). Focal encapsulated mass (5 cases), Tolosa-Hunt syndrome (2 cases)
      perineuritis (1 case) and periscleritis (1 case) were the other types of orbital
      pseudotumors. The response to treatment was known for 60 of the 84 radiologically
      classified cases. High-dose oral corticosteroid treatment was successful in 35
      out of 60 (58.3%) cases and radiotherapy in 9 out of 14 (64.3%) cases resistant
      to corticosteroids. One resistant case responded to cyclophosphamide and 2 cases
      with focal mass lesions were treated with orbitotomy. Four additional cases had
      spontaneous remission. Overall, 51 out of 64 patients (79.7%) had an eventual
      good outcome. In conclusion, we found open biopsy to be a safe and reliable
      procedure in orbital pseudotumors with the exclusion of acute phase cases. The
      success rate of treatment for this group of orbital disorders is high with the
      exception of certain disease patterns.

PMID- 8739690
TI  - Retrobulbar neuritis in a patient with acquired immune deficiency syndrome.

PMID- 8739691
TI  - Corneal phaeohyphomycosis due to Exserohilum rostratum. A case report and brief
      review.
AB  - We report a rare case of corneal phaeohyphomycosis due to Exserohilum rostratum
      following organic trauma. A known cause of cutaneous and subcutaneous
      phaeohyphomycosis, this fungus has been very rarely associated with infections of
      the eye. Being a plant pathogen, along with other saprophytic dematiaceous fungi
      the possible role in keratomycosis is discussed.

PMID- 8739692
TI  - An unusual intraocular foreign body.
AB  - Retained intraocular cilia embedded in the retina are extremely rare. A report of
      an unusual case of cilia embedded in posterior retina is presented along with a
      review of available literature. A 22-year-old male presented with a history of
      diminished vision and metamorphopsia 1 month after the successful repair of an
      ocular perforation. Anterior segment examination revealed a sutured
      superotemporal limbal tear with a surgical iris coloboma and a normally
      positioned clear lens. Ophthalmoscopic examination revealed a normal optic disc,
      macular striations and 2 cilia embedded in the retina approximately 2 disc
      diameters superotemporal to fovea. Vitrectomy with removal of cilia and endolaser
      was performed. This unusual case shows that cilia may become embedded
      intraocularly during an ocular perforation and that transvitreal removal may be a
      preferred mode of therapy with the availability of sophisticated vitreoretinal
      instrumentation.

PMID- 8739693
TI  - The amount of lens exfoliation and chamber-angle pigmentation in exfoliative
      syndrome with or without glaucoma.

PMID- 8739694
TI  - Blindness and poverty go hand in hand.

PMID- 8739695
TI  - Uncemented total hip replacement and thigh pain.
AB  - We reviewed 145 consecutive patients who had total hip replacements using
      uncemented CLS Spotorno femoral stems which achieve primary fixation with bony
      ingrowth which occurs later mainly in the metaphyseal region. The mean age was
      54.9 years and average follow up 7.8 years. The Merle d'Aubigne and Harris hip
      scores were used for evaluation, together with plain radiographs. Current medium
      term follow up showed a survival rate of 96.7% and a good functional score in
      more than 90%. Special attention was paid to postoperative thigh pain which
      occurred in only one patient. These results are encouraging, but a follow up of
      more than 10 years is required before comparable results to cemented stems can be
      claimed.

PMID- 8739696
TI  - Loosening of threaded acetabular cups in arthroplasty of the hip. The association
      with different types of coxarthrosis.
AB  - Seventy-nine patients underwent hip arthroplasty using a threaded acetabular cup
      during 1988 and 1989. Out of 71 cups implanted for coxarthrosis, radiographs of
      62 have been reviewed at a mean follow up of 69 months. The survival rate at 5.5
      years was 77.5%. The mean age at operation was 61 years. Loosening of the cup
      occurred in 7 cases with pain on walking; 5 had a revision operation. In another
      28 patients, radiolucent lines greater than 1 mm were found around the cup and 7
      of these were unstable. The previous coxarthrosis was classified as atrophic with
      5 loose cups, normotrophic with 2 loose cups and hypertrophic with no loosening.
      This difference between loosening in the atrophic and hypertrophic types of
      preexisting coxarthrosis was statistically significant. Radiolucent lines were
      present in 61% of the atrophic cases, 53.4% of the normotrophic and 25% of the
      hypertrophic, which was also significant. If the cases of loosening are added to
      those with radiolucent lines, the types of coxarthrosis show highly significant
      differences. Threaded cups had a high percentage of failure which was greater in
      cases with atrophic coxarthrosis.

PMID- 8739697
TI  - Prevention of fatal pulmonary embolism with warfarin after total hip replacement.
AB  - We studied retrospectively the efficacy of low-dose warfarin for the prevention
      of fatal pulmonary embolism in 1140 patients (1280 hips) undergoing total hip
      replacement between 1972 and 1989. The first dose, 10-20 mg, was given the night
      before operation and the regime was continued for 2 weeks after the procedure.
      Anticoagulation was aimed at achieving a therapeutic level in 4 to 5 days. All
      the patients were followed for 3 months. Seven died during this period and
      autopsy showed that 2 (0.16%) died from pulmonary embolism, one at 3 days and the
      other 10 days after operation. Pulmonary embolism causing symptoms, but which was
      not fatal, occurred in 32 patients (2.5%). Symptomatic deep vein thrombosis was
      present in 45 patients (3.5%). There were 14 (1.1%) massive postoperative
      haematoma, and 7 needed operative treatment. Low-dose warfarin can be recommended
      as a safe and efficient method of achieving an acceptably low incidence of
      postoperative thrombo-embolic complications after total hip replacement.

PMID- 8739698
TI  - The effect of ultrasonographic screening on the incidence of developmental
      dislocation of the hip.
AB  - The effect of ultrasonographic screening and treatment with a Pavlik harness on
      the incidence of developmental dislocation of the hip has been studied
      retrospectively. Observations were made at three different consecutive periods;
      in the first, clinical screening was carried out, in the second, ultrasonography
      was added for children up to 3 months of age, and in the third ultrasonography
      was used within the first few days of birth. A significantly decreased
      dislocation rate was demonstrated in each group, suggesting that early
      ultrasonography was of value in the early detection of dislocation.

PMID- 8739699
TI  - Subtalar dislocation. A study of nineteen cases.
AB  - This is a retrospective study of 19 cases of subtalar dislocation treated in our
      Department during the last 15 years. The average age of the patients was 31, and
      the majority were male (63%). Medial dislocations predominated (84%) and 37% were
      open. Associated osteocartilaginous lesions were very frequent and affected 13
      patients (68%). Surgery was required for all the open injuries and for 2 of the
      closed dislocations. Closed reduction was impossible in one, and another required
      surgery to treat an associated vascular injury. Seventeen of the 19 patients were
      reviewed after an average of 7.9 years. The results were good in 6, fair in
      another 6, and poor in the remaining 5. The results of all the open lesions was
      only fair or poor. Four patients needed a triple arthrodesis. Factors resulting
      in a poor result were open lesions, associated bone lesions, and prolonged
      immobilization.

PMID- 8739700
TI  - The role of interfascicular nerve grafting after gunshot wounds. A report of 44
      cases.
AB  - In this study the authors present the results of 44 patients with 49
      interfascicular nerve grafting procedures necessitated by gunshot wounds. The aim
      was to establish the effectiveness of microsurgical interfascicular nerve
      grafting for war injuries. The 49 interfascicular nerve grafting procedures were
      performed between July 1991 and January 1993. All but one were performed within 6
      months of injury. Nerve recovery was assessed independently by a neurologist. The
      M/S scale was used for median, ulnar and radial nerves, and the grading scale
      recommended by Millesi was used for the sciatic, tibial and peroneal nerves.
      Follow-up was for between 2.5 and 3.5 years. Patients scoring at least M3/S3+, or
      Grade 2 on the Millesi scale, were considered to have useful functional recovery
      which occurred in high median (0 out of 1), low median (4 out of 9), high ulnar
      (0 out of 2), low ulnar (5 out of 11), high radial (4 out of 6), low radial (2
      out of 2), sciatic (5 out of 9), peroneal (4 out of 7), and tibial (2 out of 2).
      The extent of recovery correlated inversely with the patient's age and the length
      of the graft, but was independent of the time between injury and surgery and of
      presumed projectile energy. Our results suggest that microsurgical
      interfascicular nerve grafting is of value in the management of wartime nerve
      injuries.

PMID- 8739702
TI  - Total knee replacement with minimally constrained prostheses in spontaneous bony
      ankylosis.
AB  - Total knee replacement has been carried out in the 4 knees of 2 patients for
      spontaneous bony ankylosis. Minimally constrained prostheses were used because
      the ligaments were usually intact and the patellofemoral and tibiofemoral joint
      lines could be re-established. The approach and repair was by a V-Y
      quadricepsplasty. Satisfactory results were obtained.

PMID- 8739701
TI  - A new technique of elbow arthrodesis. A case report.
AB  - Many techniques of elbow arthrodesis have been described. We have found them to
      be technically challenging. Our case report concerns a new technique of elbow
      arthrodesis using a reconstruction plate and compression screw. In our patient a
      satisfactory clinical result and sound union were achieved. We recommend further
      use of this technique.

PMID- 8739703
TI  - Patellar complications after total knee arthroplasty.
AB  - One hundred total knee arthroplasties implanted between 1989 and 1993 in 70 women
      and 30 men (average age 67.4 years) have been retrospectively reviewed. Six late
      patellar complications occurred: two fractures, two subluxations, one dislocation
      and one loosening. Four had a further operation. The patient's age, type of
      implant, lateral patellar release, thickness of the implant and the final range
      of movement were studied. Complications have been more common in men (8.7%) than
      women (5.2%) with a statistically significant difference (p < 0.05). This may be
      because men make a greater functional demand on their arthroplasties. No other
      factors were relevant.

PMID- 8739704
TI  - Osteoarticular manifestations of congenital insensitivity to pain with
      anhydrosis.
AB  - We report the case history of a boy who suffered from congenital insensitivity to
      pain with anhydrosis. We discuss the orthopaedic disorders occurring in 21 cases
      reported in the literature.

PMID- 8739705
TI  - [Use of a custom made femoral prosthesis in the treatment of a femoral agenesis].
AB  - We describe the management of femoral agenesis in a young adult. Following
      previous treatment, including limb lengthening by the Ilizarov technique, the
      patient was left with 30 cm of shortening, a hip fused in abduction and external
      rotation, an ankylosed knee and an ankle which had been surgically fused. We
      decided to create a mono-segmental stump, based on a mobile hip, in order to
      accommodate a suitable prosthesis. Replacement arthroplasty of the hip was first
      undertaken using a femoral component with a long stem which crossed the knee into
      the upper tibia. This allowed correction of the rotational deformity and fusion
      of the knee in an appropriate position. Amputation above the ankle was then
      carried out under the same anaesthetic. A suction prosthesis was attached to the
      stump. The arthrodesis of the hip was the principle factor in deciding on this
      procedure rather than a Van Ness operation or further lengthening. The result at
      3 years is satisfactory and the patient has good mobility.

PMID- 8739706
TI  - Multiple congenital synostosis of the upper limb associated with ulnar hypoplasia
      and cleft hand. A case report.
AB  - A girl, 15 years of age, with humeroradial, humero-ulnar, intercarpal and
      intermetacarpal synostosis, associated with a deficient ulna and a cleft hand, is
      described. Classification was difficult. She was fitted with a prosthesis.

PMID- 8739707
TI  - Lumbosacral dumb-bell neurilemmoma approached by microsurgical interlaminar
      foraminotomy. A case report.
AB  - The case history of a patient with a dumb-bell neurilemmoma arising from the L5
      nerve root is described. The tumour extended into the outlet of the neural
      foramen at L5-S1 on the left and was also compressing the dural sac and the S1
      nerve root. A limited laminotomy at L4-5 and L5-S1, with preservation of the
      neural arch, was followed by microsurgical medial foraminotomy at L5-S1 which
      allowed visualisation of the nerve root and enucleation of the tumour. The
      technique maintains stability of the posterior elements and spinal movement, and
      is recommended for the removal of this type of tumour.

PMID- 8739708
TI  - Metastatic tumours of the hand. A case report.
AB  - Skeletal metastases of neoplastic lesions are common but are rarely encountered
      in the hand. We describe a patient who presented with metastases to the hand and
      who died one year later of squamous cell carcinoma of the lung. The aetiology,
      clinical findings and treatment of neoplastic metastases of the hand are
      discussed.

PMID- 8739709
TI  - Bilateral anterior dislocation of the hips. A case report.
AB  - A case of traumatic bilateral anterior dislocation of the hips complicated by a
      femoral head fracture is described. The mechanism is discussed and the literature
      reviewed.

PMID- 8739710
TI  - Palmer's "golden week" revisited.

PMID- 8739711
TI  - The tendon defect after anterior cruciate ligament reconstruction using the
      midthird patellar tendon--a problem for the patellofemoral joint?
AB  - Retrospective clinical and radiographic evaluation was performed on 41 patients
      seen at the Salzburg General Hospital Department of Traumatology on average 2
      years following ACL reconstruction. In 26 patients (61%) clinical examination
      revealed pain trigger points over the donor site of the midthird patellar tendon
      and in the patellofemoral joint. Functional pain during kneeling activities was
      observed in 19 patients (46%). Objective measurement of the length of the
      patellar tendon in bilateral radiographs demonstrated exactly equal patellar
      tendon length in both knees in 11 patients (27%). The radiographs showed tendon
      shortening following harvesting of the midthird patellar tendon by 1-3 mm in 7
      patients (17%), by 4-6 mm in 16 (39%), and by 6-9 mm in 7 (17%). Average length
      change in the patellar tendon on the donor side was -3 mm, representing a
      patellar tendon shortening of 9.8%. On the basis of the OAK score, however, good
      and very good results were recorded in 33 patients (80%). On the whole, these
      good overall results were compromised only be patellar tendon defect morbidity.
      In addition to the local scarring problems at the donor site, shortening of the
      patellar tendon was observed with changes to patella position and interference
      with the mechanics of the patellofemoral joint. Tendon shortening can be
      explained on the basis of cicatricial contraction in the process of autorepair to
      the tendon defect. The problems affecting the patellofemoral joint are inherent
      in the therapy and must be treated as a negative factor. In the case of patients
      whose work requires mainly a kneeling position and those who make significant
      functional demands of the extension system of the knee, a critical assessment is
      required of the use of the midthird patellar tendon for anterior cruciate
      ligament reconstruction.

PMID- 8739712
TI  - Temperature changes in the knee joint during arthroscopic surgery.
AB  - Normal joint conditions are altered during arthroscopic surgery, and these
      changes have uncertain ultrastructural and biomechanical effects on articular
      cartilage. Experimental studies have shown that temperature variations affect the
      biomechanical properties of articular cartilage. We documented the temperature of
      the knee joint in 40 patients at the beginning and end of an arthroscopic
      procedure (anterior cruciate ligament reconstruction or meniscectomy). The intra
      articular measurements were obtained using a digital thermometer connected to a
      sterile stainless steel probe. Correlation coefficients and linear regression
      techniques were used to determine which variables are independent predictors of
      joint temperature at the end of surgery. The mean knee joint temperature before
      surgery was 35.1 degrees +/- 1.0 degrees C and at the end of surgery 24.6 degrees
      +/- 1.5 degrees C. The joint temperature at the end of surgery was significantly
      affected by the temperature of the saline irrigant used and the length of
      arthroscopic procedure. The clinical implications of our findings must be
      clarified in animal models.

PMID- 8739713
TI  - Effect of pretension in reconstructions of the anterior cruciate ligament with a
      Dacron prosthesis. A retrospective study.
AB  - To study the effect of the pretension level in reconstructions of the anterior
      cruciate ligament (ACL) we examined 26 patients with isolated ACL insufficiency
      and intact Dacron ligament prosthesis at 4-year follow-up. The patients were
      divided into two groups of 13 each, based on pretension level applied at the
      reconstruction: in group I the ligament was pretensioned to 60 N and in group II
      to 40 N. The patients were evaluated by the Tegner and Lysholm scores, KT-1000
      arthrometer measurements, and isokinetic muscle performance testing and were
      assessed by the Knee Ligament Standard Evaluation Form of the International Knee
      Documentation Committee. At follow-up there were no differences between the two
      groups in any of the evaluated parameters except for squatting ability. The two
      groups differed significantly (P < 0.01) with regard to the squatting score: 11
      patients in group I had decreased squatting ability, and 6 of these were not able
      to squat beyond 90 degrees of flexion. In contrast, only 4 patients in group II
      had slightly impaired squatting ability. It is likely that this difference
      between the two groups is related to the magnitude of the pretension applied to
      the ligament prosthesis, and that the pretension exerts its influence through a
      change in the knee kinematics introduced at the time of the reconstruction.

PMID- 8739714
TI  - Arthroscopic portals: the importance of blade selection.
AB  - Arthroscopy of the knee is a commonly performed procedure with a low reported
      complication rate. We have experienced two cases during which no. 15 scalpel
      blades disengaged from the handle and remained within the joint. Although both
      the blades were successfully retrieved arthroscopically without injury to the
      knee, the procedures were prolonged, and there remained a potential risk of
      causing damage. We have subsequently altered our practice and now routinely use a
      no. 11 blade, with which we have had no complications. We discuss the importance
      of correct blade selection and surgical technique in avoiding this complication
      and present two illustrative case histories.

PMID- 8739715
TI  - Chondral damage and age depress the long-term prognosis after partial
      meniscectomy. A 12- to 15-year follow-up study.
AB  - The effect of chondral damage and age on the long-term prognosis after partial
      meniscectomy was investigated in two matched groups of patients (n = 40), one
      with intact and the other with severely disrupted cartilage at the time of
      operation. Twelve to 15 years after meniscectomy a clinical and radiographic
      examination was done. Significantly more patients with intact cartilage (85%)
      than with chondral damage at operation (50%) had excellent or good knee function
      (P < 0.05). The activity levels decreased from active individual sports to
      physical fitness activities (P < 0.001), equally in both groups. Joint space
      reduction on roentgenograms was seen in 16 patients (80%) with chondral damage
      and in 6 patients (30%) with intact cartilage (P < 0.001). In addition to
      chondral damage, age over 30 years (P < 0.04) at the time of operation was
      associated with a worse functional (P < 0.03) and radiographic (P < 0.01)
      outcome.

PMID- 8739716
TI  - Recurrent acute hemarthrosis after anterior cruciate ligament reconstruction.
      Report of an unusual complication and a review of the literature.
AB  - Arthroscopic-assisted and endoscopic operative techniques have allowed for less
      and less restrictive postoperative rehabilitation programs after cruciate
      ligament reconstruction. Accelerated rehabilitation programs may, however, also
      provoke mechanical problems at the transplant-bone interface, as reports in the
      literature of loosened fixation devices and loosened or even fractured bone pegs
      with subsequent hemarthrosis and recurrent instability have shown. We describe
      the case of a patient who presented with recurrent acute hemarthrosis after
      anterior cruciate ligament reconstruction without additional trauma and without
      instability. However, the symptoms and signs were clearly related to the fixation
      method employed.

PMID- 8739717
TI  - Proprioceptive function of the shoulder girdle in healthy volunteers.
AB  - In 27 healthy volunteers (9 females, 18 males) we evaluated the proprioceptive
      function of the glenohumeral joint. The volunteers were asked to place the arm in
      different positions with and without visual control. The test was performed for
      the dominant and for the nondominant extremity. The following joint positions
      were measured: 50 degrees, 100 degrees, 150 degrees abduction; 50 degrees, 100
      degrees, 150 degrees flexion; +45 degrees, 0 degrees, -45 degrees rotation in 90
      degrees abduction. Joint position was documented with a motion-analyzing system
      with passive reflecting markers. The results showed significant differences
      between the measurements with and without visual control. Proprioception was
      worse below the shoulder level (50 degrees abduction, flexion). Two volunteers
      with generally good coordinative capabilities showed better results than the rest
      of the group. We observed no differences between dominant and nondominant
      extremities nor between males and females. Our results demonstrated low variance
      of the proprioceptive function of the glenohumeral joint in healthy volunteers.
      Our findings serve as a base for further evaluations in different patients'
      populations.

PMID- 8739718
TI  - Mechanical properties of the long head of the biceps tendon.
AB  - In this study, the geometric and mechanical properties of the long head of the
      biceps tendon were determined in order to elucidate its role in shoulder
      stability. We used a laser-micrometer system to measure the cross-sectional area
      and shape of seven fresh-frozen tendons at three levels: proximal, middle, and
      distal levels. The cross-sectional areas were found to be 22.7 +/- 9.3 mm2, 22.7
      +/- 3.5 mm2, and 10.8 +/- 2.7 mm2, respectively. While statistically significant
      differences could not be demonstrated between the magnitudes of the areas, a
      consistent difference in shape was noted between the proximal and middle levels,
      the tendon being flatter as it progressed over the humeral head and more
      triangular as it passed through the bicipital groove. We then performed cyclic
      relaxation tests and uniaxial tensile testing of the tendons which revealed a
      cyclic stress relaxation of 18 +/- 4% over ten cycles. All tensile failures
      occurred within the mid-portion of the tendon substance. Additionally, the
      modulus was calculated between 3% and 6% strain and found to be 421 +/- 212 MPa,
      while the ultimate tensile strength, ultimate strain, and strain energy density
      were 32.5 +/- 5.3 MPa, 10.1 +/- 2.7 %, and 1.9 +/- 0.4 MPa, respectively. These
      mechanical properties of the long head of the biceps tendon are of the same order
      of magnitude as tendons from other joints. The high stiffness of this tendon
      indicates that it has an ability to support the large load transferred to it by
      the muscle and to act as a humeral head depressor.

PMID- 8739719
TI  - Iliopsoas haematoma in an adolescent Taekwondo player.
AB  - A 16-year-old male Taekwondo player was admitted with a 1-day history of right
      groin pain and a palpable mass in the right lower abdominal quadrant following a
      Taekwondo training session. No history of direct trauma was given, but the pain
      followed a high inward-to-outward kick. The patient was not on any medication,
      and tumour and infection were excluded. A high-resolution real-time ultrasound
      scan identified a well-defined, hyperechoic, heterogeneous mass in the substance
      of the right iliopsoas muscle, compatible with a collection of partially clotted
      blood, confirming the clinical diagnosis of iliopsoas haematoma. After
      conservative treatment the patient resumed training and is now fully
      asymptomatic.

PMID- 8739720
TI  - Ultrasound for diagnosis of apophyseal injuries.
AB  - Avulsion injuries of the apophysis is a problem in young athletes. A correct
      diagnosis is necessary for establishing the appropriate treatment and the
      rehabilitation program. However, it is often difficult to distinguish between a
      simple muscle strain and an avulsion fracture. The X-ray examination is helpful
      only when an ossification center of the apophysis exists. Ultrasonography is
      considered the suitable diagnostic tool for these cases. From June 1988 to June
      1993, 243 young athletes were seen with an anamnestic and clinically suspected
      apophyseal injury of the lower extremity. In all cases X-ray examination and
      ultrasound examination were performed. In 80 cases the diagnosis was confirmed by
      X-ray examination and in 97 by ultrasonography. Four criteria were defined for
      the sonographic examination: (a) a hypoechogenic zone, (b) increased distance to
      the apophysis, (c) dislocation of the apophysis, and (d) mobility of the
      apophysis on dynamic examination. These criteria are correlated to (a) edema, (b)
      lysis, (c) avulsion, and (d) unstable avulsion of the apophysis. Ultrasonography
      is a proven technique for the detection of apophyseal injuries. In comparison to
      X-ray examination, it has the advantages of no radiation exposure, early
      detection even without ossification center, and dynamic examination.

PMID- 8739721
TI  - Fixation strength of interference screw fixation in bovine, young human, and
      elderly human cadaver knees: influence of insertion torque, tunnel-bone block
      gap, and interference.
AB  - A failure analysis of interference screw fixation was performed to test the
      hypothesis that bovine and/or elderly human cadavers are appropriate models for
      bone-patellar tendon-bone anterior cruciate ligament (ACL) reconstruction
      fixation studies. Failure mode is an important criterion for validating
      experimental models. The bovine, young human, and elderly human failure loads
      were 799 +/- 261 N, 655 +/- 186 N, and 382 +/- 118 N, respectively, and the
      failure modes were 75%, 69%, and 30% tissue failures, respectively. The
      similarities between the bovine and young human models in failure loads and
      failure modes indicate that bovine models are appropriate for ACL reconstruction
      fixation studies. The statistically significant differences between the young
      human and elderly human models in failure loads and failure modes indicate that
      elderly human cadavers are not an appropriate model for ACL reconstruction
      fixation studies. The differences in failure modes are consistent with previous
      studies using elderly human cadavers in which the predominant failure mode was
      bone block pullout. The tissue failures observed in the bovine and young human
      models contradict previous studies suggesting fixation strength is the weakest
      link in bone-patellar tendon-bone ACL reconstruction. Results of linear
      regression modeling showed statistically significant correlations between
      insertion torque and failure load (R2 = 0.44, P < 0.0001) and interference
      (defined as the screw outer thread diameter minus the tunnel-bone block gap) and
      insertion torque (R2 = 0.18, P = 0.003) when data from all models was combined.
      Results for the bovine model multiple regression showed a statistically
      significant regression of insertion torque (linear) and interference (quadritic)
      versus failure load (R2 = 0.56, P = 0.02). Regression slopes for screw diameter
      (P = 0.52) and gap size (P = 1.00) were not statistically significant. These
      results indicate that insertion torque and interference are independent
      predictors of failure load and should be included in future interference screw
      studies in addition to bone block dimensions, tunnel size, gap size, and screw
      diameter. Clinicians may consider using insertion torque and interference as
      indicators of postoperative graft fixation regarding rehabilitation decisions.

PMID- 8739722
TI  - The weight-bearing knee after anterior cruciate ligament rupture. An in vitro
      biomechanical study.
AB  - Unilateral weight bearing was simulated on 12 cadaver knees to quantitate
      anterior tibial translation (ATT) after anterior cruciate ligament (ACL)
      transection and to asses the role of the posteromedial structure and the
      hamstrings in controlling laxity. With the ACL intact, ATT was 3.5 +/- 2.8 mm in
      extension and 4.3 +/- 3.6 mm at 60 degrees flexion. After sectioning the ACL, ATT
      was 6.5 +/- 4.7 mm in extension and 17.5 +/- 10 mm at 60 degrees flexion (P =
      0.001). Applying a force in the hamstrings was unable to correct the pathological
      ATT observed after ACL section. Partial medial meniscectomy did not increase ATT
      after the ACL section. Disinsertion of the posterior horn of the medial meniscus
      and total medial meniscectomy increased ATT significantly compared to isolated
      ACL section. After ACL transection, sectioning the meniscotibial fibers or
      posteromedial capsule significantly increased ATT (6.5 +/- 0.5 mm in extension).
      Section of the postero-oblique ligament or popliteus tendon had no effect on ATT.

PMID- 8739723
TI  - A biomechanical analysis of joint contact forces in the posterior cruciate
      deficient knee.
AB  - The approach to the posterior cruciate deficient knee is controversial. The
      purpose of this study is to document the biomechanical changes in the static
      cadaveric knee model with simulated physiological loads. Nine fresh cadaveric
      knees from young donors (aged under 45 years) were mounted on a materials testing
      machine. Loading was carried out at 0 degrees, 30 degrees and 60 degrees to 1.5
      kN with low-pressure sensitive Prescale film (Fuji; Tokyo, Japan) inserted
      through arthrotomies into the medial and lateral compartments. Computerized
      analysis of the imprints on the film was then carried out. Tests were then
      repeated after cutting the posterior cruciate ligament (PCL). Results demonstrate
      a statistically significant posterior subluxation of the tibia on the femur at 60
      degrees flexion. This causes a significant increase in contact pressure and
      pressure concentration on the medial compartment of the knee after cutting the
      PCL. This may help explain the long-term degenerative changes observed in the
      medial femoral condyle after cutting the PCL.

PMID- 8739724
TI  - Historical overview of operations for anterior cruciate ligament rupture.
AB  - The evolution of the surgical management of anterior cruciate ligament rupture is
      critically reviewed. Special attention is paid to obsolete techniques or concepts
      which were once accepted with enthusiasm and important work that passed
      unnoticed.

PMID- 8739726
TI  - Secular changes of twinning rates in Nordic populations.

PMID- 8739725
TI  - Arthroscopic osteochondral autograft transplantation in anterior cruciate
      ligament reconstruction: a preliminary clinical study.
AB  - The high incidence of chondral defects of the femoral condyles associated with
      chronic ACL tears is widely recognised. However, treatment is difficult and
      controversial. This preliminary report presents our experience with arthroscopic
      osteochondral autograft transplantation in ACL-deficient knees. The series
      consists of 12 cases of arthroscopic osteochondral autograft transplantation in
      conjunction with ACL reconstruction using bone-patellar tendon-bone autograft;
      eight procedures were primary, and four were revisions of failed synthetic
      grafts. The patients' ages ranged from 22 to 42 years. There were ten male and
      two female patients. Chondral lesions in this series ranged from 10 to 22 mm in
      diameter. Donor site was selected prior to notchplasty, and three to five
      osteochondral cylinders, 5-10 mm in diameter, 10-15 mm long, were harvested.
      Improved surgical technique, tubular cutting instruments enabling minimal damage
      to harvested articular cartilage, and press-fit insertion yielded promising
      uniform results in ten of 12 cases with 2 years' follow-up. This study addresses
      the important issue of articular cartilage defects in ACL-deficient knees and
      possible prevention of premature joint degeneration. The aim of arthroscopic
      osteochondral autograft transplantation is to slow down the development of
      osteoarthrosis.

PMID- 8739727
TI  - Annual variation of sex ratio in twin births and in singletons in Brazil.
AB  - The annual variation of the sex ratio (SR) of 1385 twin births was analyzed and
      compared to that of 85909 singletons. These births referred not only to live
      births but also to stillbirths in two southeastern Brazilian maternity hospitals
      from 1984 to 1993. While the annual variation of the SR of singletons was very
      small, that of twin births was extremely high, due to the significant
      heterogeneity of the annual data. It is suggested that the large SR annual
      variation of the twin birth might be a consequence of the variation of male or
      female monozygotic twins. The hypothesis that twin births show a lower sex ratio
      than singletons could be supported by the present data.

PMID- 8739728
TI  - The childhood growth of twin children.
AB  - The objective of this study was to assess the childhood growth of twin children
      in terms of the effects of intrauterine growth retardation (IUGR) and discordancy
      at birth on the incidence and severity of stunting and discordancy in current
      height and weight. The study was part of a cross-sectional field project
      conducted at the Annual Twins Days Festival in Twinsburg. Ohio, USA, during 1990,
      1991, and 1993, and including all twin children between 2 and 12 years of age.
      Mothers of twins were interviewed regarding their children's birthweights and
      gestational age; the twin children were measured for their current heights and
      weights. The study population included 990 twin children, including 555 boys and
      435 girls, of which there were 254 boy pairs and 194 girls pairs. Birthweight for
      gestational age and current weight and height were each converted into Z-scores
      and characterized as severe (Z-score < -2,0), or moderate IUGR or stunting (Z
      score > -2.0 and < -1.2). For the present study discordancy in birthweight, and
      current height and weight was calculated for like-gender twin pairs. Only twin
      children with severe IUGR at birth showed an increased risk of stunting in their
      current height or weight, and this risk was only for moderate, not severe,
      stunting. Boy twins with severe IUGR at birth were at increased risk of moderate
      stunting in their current weight (OR 2.67, 95% CI 1.55, 4.58, p = 0.002), while
      girl twins with severe IUGR at birth were at increased risk of moderate stunting
      in their current height (OR 4.09, 95% CI 1.49, 10.99, p = 0.003). Among like
      gender twin pairs, there were no differences in mean or categories of birthweight
      or current weight discordancy, but boy twin pairs did show a significantly
      greater proportion of current weight discordancy compared to girl twin pairs (p =
      0.005). Overall, there was a significant tendency for differences in height and
      weight between like-gender twin pairs to disappear over time, with the effect
      being greater for boy twin pairs. We conclude from these findings that twin
      children tend to overcome growth retardation and discordancy present at birth,
      and although children who had severe IUGR or discordancy at birth were more
      likely to have some residual moderate stunting or discordancy in height or
      weight, they still tended to be within normal values for their gender and current
      age.

PMID- 8739729
TI  - Eight-year follow-up of cognitive development in 33 twin pairs.
AB  - This is a follow-up study of twins, including 33 twinpairs from the Stockholm
      area, aiming to study the cognitive development of twins at eight years of age.
      The twins have been followed at different ages from birth onwards. All children
      were tested with the Wechsler Intelligence Scale for Children in a Swedish
      translation (WISC). The WISC test consists of a Verbal and a Performance Scale.
      There were no significant differences between twin girls and twin boys on these
      Scales. On the Performance subtests Block Design, Object Assembly, and Coding,
      however, the twin girls performed significantly better than the twin boys. In
      comparing cognitive development for twins and singletons, the twin group had
      somewhat lower average scores than the singletons. Prematurity and low birth
      weight continued to be related to cognitive development at eight years of age.
      Also at this age the school teacher completed a questionnaire about the twins
      social behaviour and some personality traits. There was a relation between one
      questionnaire factor, a low score of assertiveness, and the mother's negative or
      ambivalent expectations concerning the twin pregnancy. The twin group with the
      mother's negative expectations also had significantly lower results on the
      subtests Comprehension and Coding. Negative mothers had more premature twins than
      mothers who were positive toward the twin pregnancy.

PMID- 8739730
TI  - Prevalence of a history of testicular cancer in a cohort of elderly twins.
AB  - Prior studies have suggested that the risk of testicular cancer among dizygotic
      twins may exceed that among monozygotic twins or the general population.
      Cryptorchidism is associated with testicular cancer and twinship, and therefore
      might potentially explain the findings of the prior studies. In 1993-1994, when
      they were 66 to 77 years of age, 14,326 twin individuals in the National Academy
      of Sciences-National Research Council Twin Registry were interviewed by
      telephone. A history of testicular cancer was reported by 5 (0.08%) of 5951
      monozygotic twins and 11 (0.16%) of 6992 dizygotic twins. Follow-up interviews
      concerning testicular cancer risk factors and treatment were able to be
      administered to 4 of the monozygotic and 9 of the dizygotic twins reporting
      testicular cancer. A history of cryptorchidism was reported in the follow-up
      interview by only one dizygotic twin. Our data agree with the results of prior
      studies reporting a more frequent occurrence of testicular cancer among dizygotic
      than monozygotic twins. Although somewhat limited by small numbers, our study
      also suggests that the findings of increased testicular cancer in dizygotic twins
      are not explained simply by increased occurrence of cryptorchidism in twins.

PMID- 8739731
TI  - Sad fetus syndrome--gestational trophoblastic disease concurrent with a living
      fetus or fetuses.
AB  - The term gestational trophoblastic disease is used to indicate a group of both
      benign and malignant trophoblast, including molar degeneration of villi, hydatid
      mole, invasive mole and choriocarcinoma. This study shows a new classification of
      trophoblastic disease existing with a living fetus or fetuses. Benign hydatid
      mole is the initial stage of the disease continuum, whereas highly malignant
      choriocarcinoma is the final stage of this spectrum.

PMID- 8739732
TI  - Intrapair differences of the blood cell components and lymphocyte subsets in
      monozygotic and dizygotic twins.
AB  - We evaluated the relative influence of genetic and environmental factors on
      leukocytes, lymphocytes, neutrophils, monocytes, erythrocytes, reticulocytes,
      hemoglobin, platelets, T lymphocyte subsets, and NK marker cells in monozygotic
      (MZ) and dizygotic (DZ) twins. Peripheral blood components were measured in 154
      healthy twin pairs (118 MZ pairs and 36 DZ pairs) and lymphocyte subsets in 48
      healthy twin pairs (38 MZ pairs and 10 DZ pairs). Platelets and erythrocytes
      showed higher intraclass correlations in the MZ pairs than in the DZ pairs in the
      males. However, in the females, the intraclass correlations for these components
      were similar between the MZ and DZ pairs. Neutrophils and monocytes showed low
      intraclass correlations in the MZ pairs. The absolute number of CD4+ cells and
      the CD4+/CD8+ cell ratio showed high intraclass correlations regardless of age in
      the MZ pairs in both males and females. The intraclass correlation for the
      absolute number of CD3+ cells was low in pairs aged > or = 60 years in the MZ
      pairs. The absolute numbers of CD16+ cells and CD56+ cells showed high intraclass
      correlations regardless of age in the MZ pairs.

PMID- 8739733
TI  - Slow twin conception at first birth and subsequent maternal twin proneness in a
      natural fertility population.
AB  - To study whether apparently more fecund women having delivered twins at first
      birth have traits of higher twin-proneness, we performed a retrospective cohort
      study on population-based historical vital records of the 17-18th century French
      Canadian immigrants and their descendants under natural fertility conditions.
      Among 24896 mothers who had at least one child, 248 had twin maternities at their
      first birth (twinning rate = 1.0%). Among 21508 mothers with a valid marriage
      first birth interval, twinning rate was 0.97% among prompt conceptions (7.0-11.0
      months), with a particularly high rate at the interval of 7.0-8.0 months (2.2%).
      Marriages in August-October resulted in a higher twinning rate particularly for
      the slow conceptions than those in the other seasons. Promptly-conceived mothers
      of twins at the first delivery may seem to have higher fecundity, but subsequent
      births from these mothers (n = 88) show a lower twinning rate (1.7%) particularly
      at younger maternal age than from the other mothers who had slowly conceived
      twins at their first birth (n = 112). The latter show a 4.5% twinning rate as a
      whole among their second or later births. So-called twin-proneness of a mother,
      whether genetic or acquired, was not connected to higher conception rate of
      twin's mothers immediately after marriage. Reduced fecundity, which may have been
      imposed by some environmental factors, could raise the chance of twinning.

PMID- 8739734
TI  - Mutations in fucosidosis gene: a review.
AB  - Fucosidosis is an autosomal recessive disorder caused by a deficiency of alpha-L
      fucosidase. Up to now 79 cases have been described and several others identified
      but not yet published. The higher incidence of the disease is in Italy, where
      nearly 20 patients have been identified. Fourteen disease-causing mutations have
      been detected and four of them, Q422X, G60D, E375X, P141fs are present in more
      than 70% of the forty patients studied. In Italian patients, only seven mutations
      have been described and P141fs and G60D mutations are present in more than 50% of
      the cases. The P141fs mutation is absent in other ethnic groups. It has been
      impossible to establish genotype-phenotype correlation so far and the clinical
      variability of the disease cannot be explained only by genetic heterogeneity.

PMID- 8739735
TI  - Ovarian hyperstimulation syndrome may be more likely if multiple pregnancy occurs
      following assisted conception.
AB  - Whereas modern assisted conception with such techniques as in vitro fertilisation
      now helps many subfertile couples to fulfill their ambition to have a child, it
      has not been without a price. The increased incidence of multiple pregnancies,
      with their attendant maternal and perinatal sequelae following assisted
      conception is well known, but perinatologists may be far less familiar with the
      Ovarian Hyperstimulation Syndrome (OHSS) which is the other major complication
      when controlled ovarian hyperstimulation is used during assisted conception
      treatment. Mild forms of OHSS are common and require no more than symptomatic
      treatment. Severe forms of OHSS are uncommon occurring in 0.6% to 14% of IVF
      cycles, but are nonetheless very important to identify as they may lead to
      thrombo-embolic disease, cardiorespiratory dysfunction, renal failure and even
      death [6]. This review considers whether OHSS may be related to multiple
      pregnancy by reviewing the available literature and local experience.

PMID- 8739736
TI  - Anal sphincter defects in fecal incontinence: correlation between endosonography
      and surgery.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic ultrasound provides accurate information
      about the anatomy of the anal sphincter. The purposes of this study were to
      evaluate the use of flexible echo endoscopes to examine the anal sphincters, to
      validate the diagnosis of internal and external sphincter defects obtained using
      echo endoscopes by comparison with surgical findings, and to assess the outcome
      after surgical sphincter repair. PATIENTS AND METHODS: Twenty-eight patients (13
      women, 15 men, median age 50 years, range 30-83) with fecal incontinence--which
      was of traumatic origin in all but one (childbirth: n = 8; anorectal surgery: n =
      17; biopsy of the prostate: n = 2; no trauma: n =1)--were prospectively
      investigated by endosonography using an echo colonoscope (n = 14) or an echo
      gastroscope (n = 14) (CF-UM20, GF-UM20, Olympus Optical). The location and extent
      of the defects of the internal or external sphincters, or both, were compared
      with the surgical findings in all patients. The surgical outcome was defined as
      excellent, improved, or unchanged. RESULTS: At surgery, 25 of the 28 patients had
      an isolated internal sphincter defect (n = 15) or combined sphincter defect (n =
      10). Endoscopic ultrasound identified all of the external anal sphincter defects
      (n = 10), and correctly excluded a defect in 15 of 18 patients (sensitivity,
      specificity, and accuracy 100%, 83% and 89%, respectively). All of the internal
      sphincter defects (n = 25) were detected by endosonography. In three patients, a
      postulated intact internal sphincter was confirmed by surgery (accuracy 100%). In
      two patients, the extent of the sphincter defect was underestimated. Despite good
      visualization of the internal and external anal sphincters, as well as of the
      puborectal muscle in all patients, the shape, diameter, and full radial image
      sector (360 degrees) of the echo gastroscope made this instrument more
      practicable than the echo colonoscope. Nineteen of 25 patients who underwent
      surgery (76%) with proved sphincter defects experienced improvement, the figure
      reaching 87% (13 of 15) in patients who received isolated internal sphincter
      defect repair. CONCLUSIONS: Anal endosonography, even using flexible echo
      endoscopes, is an accurate method for identifying anal sphincter defects, and is
      the method of choice for preoperative sphincter mapping with special regard to
      internal sphincter repair, which can be carried out with excellent results.

PMID- 8739737
TI  - Palliation of malignant gastric outlet obstruction with self-expanding metal
      stents.
AB  - BACKGROUND AND STUDY AIMS: Self-expanding metal stents have long been used in the
      management of patients with malignant esophageal and malignant biliary
      obstruction. The aim of the present study was to report on the palliation of
      malignant gastric outlet obstruction using self-expanding endoprostheses.
      PATIENTS AND METHODS: Between March 1993 and December 1994, 12 patients (eight
      women, four men, mean age 64 years) suffering from malignant gastric outlet
      obstruction due to recurrent gastric carcinoma (seven patients) and pancreatic
      head carcinoma (five patients) presented with an inability to eat and intractable
      vomiting. The patients were managed with peroral insertion of self-expanding
      metal stents. RESULTS: Peroral introduction of the stent with the aid of a
      stabilizing overtube was successful in all patients, with the stent being
      supported as it was being advanced through the stenosis. Proper release of the
      stent into the stenotic area was achieved in all cases, relieving the intractable
      vomiting. The procedure was accomplished without any complications. All patients
      were able to eat semisolid food four days after the stent insertion. Apart from
      an asymptomatic partial stent occlusion in one patient, no other complications
      were seen during the short-term follow-up one, two, and three months after
      discharge. CONCLUSIONS: These preliminary results suggest that self-expanding
      stents can effectively relieve malignant gastric outlet obstruction.

PMID- 8739738
TI  - Ulcer site and complications: relation to Helicobacter pylori infection and NSAID
      use.
AB  - BACKGROUND AND STUDY AIM: The aim of this study was to investigate the
      relationship between the presence and location of ulcers, H. pylori infection,
      NSAID use, and major upper gastrointestinal tract bleeding. PATIENTS AND METHODS:
      We studied 100 consecutive patients with duodenal ulcers and 145 consecutive
      patients with benign gastric ulcers. RESULTS: Ninety-nine percent of the duodenal
      ulcer patients and 92% of the gastric ulcer patients had H. pylori infection; all
      gastric ulcer patients without H. pylori infection were using NSAIDs. Gastric
      ulcers in patients with H. pylori infection who were not using NSAIDs were more
      likely to be on the lesser curvature (85%) than ulcers in NSAID users who had no
      H. pylori infection (35%) (p < 0.01). Conversely, only 5% of gastric ulcers in H.
      pylori-positive patients who were not using NSAIDs were on the greater curvature,
      compared to 45% in H. pylori-negative NSAID users (p < 0.01), and 23% in patients
      with both possible etiologies. The frequency of NSAID use was very high in
      patients presenting with upper gastrointestinal tract bleeding: 21 of 25 with
      gastric ulcers (84%) and 13 of 21 with duodenal ulcers (62%; p < 0.01 for each,
      compared to bleeding without taking NSAIDs). Overall, 74% of patients with upper
      gastrointestinal hemorrhage from peptic ulcer were taking NSAIDs. The prevalence
      of H. pylori infection was similar among the ulcer patients presenting with and
      without upper gastrointestinal tract bleeding. CONCLUSIONS: The location of a
      gastric ulcer on the greater curvature, and presentation with upper
      gastrointestinal tract bleeding, are separate and valuable clues to the
      involvement of NSAIDs. NSAID use may now be responsible for most bleeding
      complications of ulcer disease, regardless of H. pylori status.

PMID- 8739740
TI  - Evaluation of undiluted N-butyl-2-cyanoacrylate in the endoscopic treatment of
      upper gastrointestinal tract varices.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic obliteration of upper gastrointestinal
      tract varices using N-butyl-2-cyanoacrylate has been proposed by some authors.
      The aim of the present study was to evaluate prospectively the efficacy and
      safety of this technique, using the undiluted substance, in obtaining hemostasis
      of bleeding upper gastrointestinal tract varices, as well as definitive
      eradication of varices located in the gastric fundus and duodenum. PATIENTS AND
      METHODS: We carried out variceal injections of N-butyl-2-cyanoacrylate in 80
      patients (51 males, 29 females, mean age 68 years, range 19-80) with upper
      gastrointestinal tract varices. In 24 patients, the varices were located in the
      esophagus, in 54 in the gastric fundus, and in the remaining two they were in the
      duodenum. Forty-eight patients were treated for active variceal bleeding, and the
      other 32 were treated electively. RESULTS: Hemostasis was achieved in 43 of the
      48 patients (89.6%) treated for active variceal bleeding. Eradication was
      obtained in 49 of the 56 patients (87.5%) with gastric or duodenal varices.
      Overall complications occurred in 11 patients (10.4%). In two patients,
      embolization was found, and in a further two patients it was clinically
      suspected, but could not be proved. Ten patients (12.5%) died during the
      treatment period, six due to uncontrolled bleeding, two due to rebleeding, and
      two due to liver failure. CONCLUSIONS: Endoscopic injection of N-butyl-2
      cyanoacrylate appears to be both safe and effective in the treatment of bleeding
      gastrointestinal tract varices. The relative value of the undiluted substance
      versus the diluted one should be further evaluated.

PMID- 8739739
TI  - The effect of endoscopic sclerotherapy of esophageal varices on the development
      of gastric varices.
AB  - BACKGROUND AND STUDY AIMS: The effect of sclerotherapy of esophageal varices on
      the development of gastric varices is a controversial question. The aim of the
      present study was to evaluate prospectively the presence and development of
      gastric varices as a consequence of esophageal variceal sclerotherapy. PATIENTS
      AND METHODS: We prospectively studied 227 patients, all of whom had liver
      cirrhosis at the time of the first bleeding episode due to esophageal varices.
      All patients were treated with emergency endoscopic sclerotherapy, and further
      courses of sclerotherapy to eradicate the varices were given at seven-day
      intervals for three sessions, and then every fifteen days until eradication was
      complete. At the time of inclusion in the study, patients were divided in two
      groups: group A, with initial gastric varices, and group B, without any gastric
      varices initially. RESULTS: Group A included 138 patients (60.8%), in 99 of whom
      (71.7%) disappearance of the gastric varices was observed. In 63 cases (63.6%)
      the varices were eliminated during the sclerotherapy treatment, before the
      eradication of esophageal varices; in 36 cases (36.4%), the gastric varices
      disappeared after the eradication of the esophageal varices. Group B included 89
      patients (32.9%); in 78 of them (87.6%), no appearance of gastric varices was
      observed, while in 11 (12.4%), gastric varices appeared. CONCLUSION: From these
      data, it can be concluded that sclerotherapy of esophageal varices cannot be a
      determinant factor either for the appearance of gastric varices or for their
      subsequent risk of bleeding.

PMID- 8739741
TI  - Severe upper gastrointestinal tumor bleeding: endoscopic findings, treatment, and
      outcome.
AB  - BACKGROUND AND STUDY AIMS: The aim of the present study was to review endoscopic
      findings, treatment, and clinical outcomes in patients with severe upper
      gastrointestinal bleeding due to tumors. PATIENTS AND METHODS: A retrospective
      analysis was made of prospectively gathered data on all patients with severe
      upper gastrointestinal bleeding who were admitted to two large referral centers
      during a 45-month period. RESULTS: Nine hundred thirty-five patients had severe
      upper gastrointestinal bleeding, of whom 42 (5%) were found to have tumors.
      Histologically, nearly all of the tumors were of a malignant type. Fifty-two
      percent of the patients had acute severe upper gastrointestinal bleeding as the
      initial presentation of their tumor. The most common tumor was gastric
      adenocarcinoma, and all of these cases were at advanced stages. Endoscopic
      hemostasis with thermal probes or epinephrine injection, or both, was carried out
      in seven patients (17%), with successful hemostasis in all of the tumors.
      Regardless of the treatment given, patients with upper gastrointestinal tumor
      bleeding, had a 30-day surgery rate of 43%, a 30-day rebleed rate of 33%, a 30
      day mortality rate of 10%, and a 1-year mortality rate of 89%. CONCLUSIONS: Most
      tumors that cause severe upper gastrointestinal bleeding are of a malignant
      histologic type and are already at an advanced stage. Endoscopic hemostasis of
      bleeding upper gastrointestinal tumors is safe and initially effective, and may
      provide time for elective surgical palliation. Regardless of therapy, upper
      gastrointestinal tumors with severe bleeding have a poor one-year survival.

PMID- 8739742
TI  - Endoscopic features of metastatic tumors in the upper gastrointestinal tract.
AB  - BACKGROUND AND STUDY AIMS: Metastatic tumors in the upper gastrointestinal tract
      are rare. The tumors that most frequently metastasize to the upper
      gastrointestinal tract are reported to be melanoma, lung cancer, and breast
      cancer. We describe here our experience in relation to the clinical
      manifestations and endoscopic findings of metastatic tumors in the upper
      gastrointestinal tract. PATIENTS AND METHODS: Excluding leukemia, lymphoma, and
      direct tumor invasion, eight cases of metastatic tumor in the upper
      gastrointestinal tract from five identified primaries were observed over a period
      of eight years. The histological nature of the lesions was verified by endoscopic
      biopsy. RESULTS: The primary tumors in the eight cases were lung cancer (two
      cases), renal transitional-cell carcinoma (two cases), colonic cancer (two
      cases), melanoma (one case) and testicular embryonal cell carcinoma (one case).
      Acute upper gastrointestinal bleeding and anemia were the most common features of
      the clinical presentation, and the stomach and duodenum were the organs most
      often involved. Endoscopically, submucosal tumors and polypoid masses, with
      either erosion or ulceration, were the usual morphological findings. CONCLUSIONS:
      Panendoscopy with histological examination is a way of identifying metastatic
      tumors to the upper gastrointestinal tract when patients have a known primary
      cancer and symptoms relating to the upper gastrointestinal tract. However, there
      is no specific information allowing the origin of a lesion to be predicted.

PMID- 8739743
TI  - A new guide wire papillotome for patients with Billroth II gastrectomy.
AB  - BACKGROUND AND STUDY AIMS: Guide wire-assisted papillotomy is a well-established
      technique in conventional biliary endoscopy, but has not been previously employed
      in Billroth II patients, due to the lack of an appropriate papillotome that can
      accommodate a guide wire. We therefore designed a Billroth II papillotome that
      can be inserted over a guide wire. PATIENTS AND METHODS: Over a 12-month period,
      24 patients (18 males, six females, median age 72 years), who had previously
      undergone a Billroth II gastrectomy and who were referred to our department for
      therapeutic biliary endoscopic procedures, were included in this study. RESULTS:
      The papilla could be reached in 22 patients, but the procedure failed in two due
      to an excessively long afferent loop. Cannulation of the bile duct with the
      standard Billroth II papillotome was possible in 11 patients; the remaining 11
      patients, in whom free cannulation failed, underwent cannulation over the guide
      wire. Diagnostic endoscopic retrograde cholangiography revealed bile duct stones
      in 17 patients, and malignant-appearing common bile duct stenoses in five
      patients. Papillotomy was successfully performed using the guide wire Billroth II
      papillotome in all patients, without complications. CONCLUSION: The Billroth II
      papillotome is effective and safe in patients in whom free cannulation has failed
      using the standard Billroth II papillotome.

PMID- 8739744
TI  - Endoscopic hemostasis of upper gastrointestinal bleeding with histoacryl: last
      resort before surgery.
AB  - Five patients presented with acute upper gastrointestinal bleeding, underwent
      diagnostic and therapeutic endoscopy. The source of bleeding was identified in
      each case. Two patients had a large chronic gastric ulcer, one had a stress
      ulcer, one had a gastric ulcer with hypertrophic gastropathy, and one had a
      malignant infiltration of the second part of the duodenum. Conventional first
      line therapeutic modalities failed to induce hemostasis in these bleeding
      lesions. Hemostasis was successfully achieved in each case using an endoscopic
      intralesional injection of Histoacryl. This agent may represent a last resort for
      endoscopic hemostasis before surgery.

PMID- 8739745
TI  - Anal endosonography in faecal incontinence.

PMID- 8739746
TI  - A minute rectal carcinoma with massive submucosal invasion and lymph-node
      metastasis.

PMID- 8739747
TI  - Upper gastrointestinal bleeding due to metastatic gastric and duodenal squamous
      cell carcinoma from the hypopharynx.

PMID- 8739748
TI  - Long-term paraprosthetic-enteric fistula only diagnosed after upper
      gastrointestinal endoscopy.

PMID- 8739749
TI  - Intraoperative endoscopic sphincterotomy during laparoscopic cholecystectomy.

PMID- 8739750
TI  - Laparoscopic cholecystectomy: a case of postoperative hemorrhage successfully
      treated by laparoscopic reintervention.

PMID- 8739751
TI  - Dilation therapy of upper esophageal webs in two cases of Plummer-Vinson
      syndrome.

PMID- 8739752
TI  - Carcinoma in situ arising in a gastric hamartomatous polyp in a patient with
      Peutz-Jeghers syndrome.

PMID- 8739753
TI  - Endoscopic demonstration of malignant duodenocolic fistula: two case reports.

PMID- 8739754
TI  - Intraductal mucin-hypersecreting neoplasm of the pancreas: endosonographic
      findings.

PMID- 8739755
TI  - Colonoscopic appearance of an adenocarcinoid of the vermiform appendix.

PMID- 8739756
TI  - Apricot-stone syndrome (Barackmag-Syndrome): a report of two cases.

PMID- 8739757
TI  - Is the intracellular pH threshold an anaerobic threshold from the view point of
      intracellular events?: a brief review.
AB  - Intracellular biochemical changes could be monitored noninvasivery and
      continuously by using nuclear magnetic resonance (NMR). In about the last decade,
      intracellular behavior of phosphorus compounds and pH during muscle contraction
      in man have been studied by 31P nuclear magnetic resonance spectroscopy (31P
      MRS). During incremental load, lactic acidosis was followed by a decline in
      intracellular pH. 31P-MRS studies has been definitely proved that this change in
      intracellular pH shows the threshold behavior. Some reports discussed the
      intracellular pH threshold (pHT) as an anaerobic threshold (AT) from the view
      point of intracellular events. However, our studies revealed that pHT did not
      reflect the onset of lactate production. In this article, studies of
      intracellular pH of working muscle were reviewed in relation to an anaerobic
      threshold.

PMID- 8739758
TI  - Effects of cooling portions of the head on human thermoregulatory response.
AB  - Seven healthy young male students participated in this study. Each subject sat on
      a chair in an anteroom at 25 degrees C for 30 min and then entered a climatic
      chamber, controlled at 40 degrees C and R.H. 50%, and sat on a chair for 90 min.
      Cooling of frontal portion including the region around the eyes (FC), occipital
      portion (OC), and temporal portion (TC) began after 50 min of entering. An
      experiment without head cooling (NC) was also made for the control measurement.
      Thermal comfort and thermal sensation were improved by head cooling, but response
      was the same regardless of portion cooled. Although rectal temperature, mean skin
      temperature and heart rate showed no significant effect due to head cooling,
      forearm skin blood flow (FBF), sweat rate (SR), and body weight loss (delta Wt)
      had a tendency to be depressed. FBF in FC and TC decreased during head cooling,
      but that in OC and NC did not change significantly, while SR in FC was depressed.
      delta Wt showed total sweating to decrease by FC and TC, and FC to have greater
      inhibitory effect on sweating than OC. Thermal strain was evaluated by the
      modified Craig Index (I(s)). I(s) in FC decreased significantly more than in NC.
      Cooling of other portions of the head had no significant effect on I(s). Cooling
      of the frontal portion of the head may thus be concluded to have the most effect
      on thermoregulatory response in a hot environment.

PMID- 8739759
TI  - Evaluation of mental strain by palm sweating during short-term memory task.
AB  - This paper reports on the investigation of palm sweating during short-term memory
      tasks and testing the availability of the amount of palm sweating for an index
      evaluating mental strain. Six male subjects performed sets of thirty tasks with
      digit strings ranging from 4 to 9 digits at random order. The correctness of
      recalled answer, subjective difficulty for mental stress and palm sweating at
      each task were recorded. The amount of palm sweating (PS) was measured using
      hygrometry with a ventilated capsule attached on the left palm. Correct answer
      rates suddenly decreased over 7 digits. Subjective difficulty tended to increase
      with an increase in string-length. PS tended to decrease exponentially with the
      repetition of tasks at each string-length, and the exponential regression curve
      was fitted between PS and order in tasks at each string-length. Estimated PSs
      were obtained at 1st, 15th, and 30th tasks from the regression curves. Estimated
      PS at 1st task tended to increase in proportion to string-length. Each estimated
      PS at both 15th and 30th tasks had a threshold for increasing. Also, estimated PS
      increased in proportion to the string-length at no less than the threshold. The
      thresholds were 5 digits at 15th and 6 digits at 30th task. These present
      findings suggest that PS is an index available for measuring mental strain. Also,
      this index describes the level quantitatively in adaptation for mental stress.

PMID- 8739760
TI  - Evaluation of static work load in a helium-oxygen saturation dive at 31 ATA.
AB  - The purpose of the present study is to evaluate the static work load as a model
      work in Submersible Decompression Chamber (SDC) during a deep sea saturation dive
      with helium-oxygen gas mixture. Heart rate (HR) and electromyogram (EMG) power
      spectrum changes were studied during a 7-minute static work, half-rising posture
      or flexed knee posture in four healthy male subjects. During the static work, EMG
      of the rectus femoris was recorded with surface electrodes, and changes in the
      EMG power spectrum were presented in the ratio of a high-frequency to low
      frequency band (H/L ratio) after the Fourier transform analysis. The HR decreased
      at 31 ATA and increased remarkably after the decompression to 1 ATA. HR at post
      decompression was higher than pre-compression. The lowering phenomena of EMG
      presented by H/L ratios during the static work were similarly observed in all
      three conditions. But the changes of the high and low frequency components were
      different in the post-decompression condition from the pre-compression and 31 ATA
      conditions. HR as a parameter of static work load might underestimate the work
      load at the hyperbaric environment due to hyperbaric bradycardia and overestimate
      it after decompression by "decompression tachycardia." The EMG lowering
      phenomenon observed after decompression might not be caused by the same mechanism
      as seen in the pre-compression and hyperbaric environments. Extreme care must be
      taken to evaluate the static work load not only at hyperbaric helium-oxygen
      environments but after decompression from a deep saturation dive.

PMID- 8739761
TI  - Postural effect on respiratory sinus arrhythmia with various respiratory
      frequencies.
AB  - Heart rate variations during steady state respiration with various frequencies
      were studied on seven healthy male students at two different body positions.
      Respiration was controlled at four different frequencies (0.083, 0.100, 0.200,
      0.250Hz), and the tidal volume was simultaneously controlled at 1500ml (0.083,
      0.100Hz) or 1000ml (0.200, 0.250Hz). A tilting bed was used for changing body
      position, and the measurements were conducted at horizontal and vertical
      position. RSA (respiratory sinus arrhythmia) amplitude at 0.250Hz was
      significantly decreased at vertical position compared with horizontal position.
      At 0.200Hz the significant decrease could not be obtained although some tendency
      of decrease appeared. Contrary to these high frequencies, the amplitudes at low
      frequencies (0.083, 0.100Hz) were significantly increased (p < 0.01) during
      vertical position. This postural effect on the low frequency RSA could be
      regarded as a similar result on MWSA (Mayer wave relate sinus arrhythmia) which
      reflects sympathetic nervous activity. Furthermore, the ratio between the
      amplitude at 0.100Hz and that at 0.250Hz was significantly correlated with mean
      heart rate (n = 56, r = 0.73). From these results it was assumed that the RSA
      amplitude at low frequency associate a with not only parasympathetic nerves but
      also sympathetic nerves whereas the amplitude at high frequency was solely
      mediated by parasympathetic nerves.

PMID- 8739762
TI  - In vitro chick pre-cardiac explant tissue differentiation during spaceflight on
      SpaceHab-02.
AB  - Chick precardiac tissue explants were cultured on the 8-day mission of STS-60,
      space shuttle Discovery. Development of in vitro cultures of precardiac chick
      tissue from embryo stages 5 though 8 (H-H) were initiated during orbit and were
      terminated after approximately fifteen hours of 37 degree C culture. Transmission
      electron microscopy and tritiated thymidine studies were performed postflight. No
      significant differences in cell proliferation were observed between flight and
      ground controls. Electron-microscopic studies revealed stage 8 explants were
      capable of differentiation during flight in a pattern which matched ground
      control tissues. As anticipated, stage 7 explant tissues had differentiated to a
      lesser extent compared to stage 8 tissues. Interestingly, stage 7 precardiac
      explant flight tissue differentiation was less than ground control tissue. This
      difference in differentiation between flight and ground cultures was enhanced in
      stage 6 tissues, as high levels of myofibril organization were only seen in
      ground controls. Other cellular components such as Golgi apparatus, junctional
      complexes, and mitochondria were present and appeared normal and healthy.

PMID- 8739763
TI  - Micromorphometric characteristics of osteons in compact bone of growing tibiae of
      human fetuses.
AB  - A micromorphometric study of compact bone from 150 tibiae of human fetuses of 6,
      7-8 and 9 months of gestation was performed. The following variables were
      determined: number of Haversian canals per mm2, distance between adjacent
      Haversian canals, mean diameter of Haversian canals, volume density of the
      Haversian canals, and volume density of developing osteons. In the earlier
      periods of intrauterine development the compact bone displays a high volume
      density of osteons, a few wide bone lamellae, wide Haversian canals with high
      relative volume and density, and a small thickness of the bone between the
      canals. Late in gestation, the bone contains osteons with many lamellae, and
      small relative volume density. Haversian canals are narrow, comparatively sparse,
      with low volume density and considerable thickness of the intercanal tissue
      layer. The differences between late and mid-gestation bone tissue are
      statistically significant.

PMID- 8739764
TI  - Abnormal spermatozoa in the cauda epididymidis of adult and aged hamsters
      (Mesocricetus auratus): a study by electron microscopy.
AB  - The morphology of the spermatozoa in the cauda epididymidis of 6- and 24-month
      old (adult and aged) hamster was studied by electron microscopy. Lesions found in
      the spermatozoa included alterations in the acrosomal matrix and nuclear
      membranes, abnormal or absent mitochondria, alterations in the axonemes, dense
      fibres and microtubules, and bent flagella. All these abnormalities are similar
      to those found in other species and few alterations were exclusive to the older
      animals. Ultrastructurally abnormal spermatozoa were observed in both groups but
      were present at a significantly greater frequency in aged hamsters (p < 0.005).
      the percentage of sperm with abnormal acrosomes, mitochondria and dense fibres
      and of bent (but not disrupted) spermatozoa was significantly greater in the
      older animals. These results show that the ultrastructural alterations in hamster
      sperm are similar to those found in other mammals. Moreover, the percentage of
      ultrastructurally abnormal spermatozoa in aged hamsters is greater than 6-month
      old hamsters, this increase is not accompanied by any new kinds of alteration.

PMID- 8739765
TI  - A scanning electron-microscopic analysis of the morphology of equine lower lip
      sinus hair.
AB  - Sinus hairs, which are tactile organs of most mammals, are differentiated into
      cavernous and sinus types. The horse has the cavernous type. Horse lower lips
      were perfused in diluted Karnovsky's fixative and sinus hair processed for
      scanning electron microscopy. Anastomosing trabeculae of different thickness and
      shape originate from the internal connective tissue layer and extend to the
      external layer, thus forming a dense meshwork suspending the hair root like a
      net. However, many of the distal trabeculae do not reach the external wall of the
      blood sinus but end in a finger-like knob within the sinus, thus sharing some
      features of the sinus type. The sinus wall and trabeculae are completely covered
      by polygonal endothelial cells showing characteristically protruding nuclei,
      sparse microvilli and distinct cell borders. Endothelial cells on the trabeculae
      are more elongated. Openings of small blood vessels were found exclusively on the
      internal wall, indicating that blood exchange occurs via the internal wall only
      and that turnover of blood may be minimal. The supposed significance and function
      of the finger-like trabeculae in the distal part of the blood sinus lying close
      to the majority of nerve terminals is discussed.

PMID- 8739766
TI  - Use of a bite-opening appliance in the miniature pig: modification of
      craniofacial growth.
AB  - The purpose of this study was to determine the growth response of pigs to a bite
      block, preparatory to investigating the functional correlates of altered growth.
      Three miniature pigs (Sus scrofa) wore bite-opening appliances, creating an
      anterior opening of 18-20 mm, for 42-67 days. Three untreated pigs served as
      controls. All animals received tantalum implants and tetracycline injections to
      track growth of the facial bones and sutures. Treatment caused relative intrusion
      of maxillary and mandibular posterior teeth, and supereruption and retroclination
      of anterior teeth. Vertical displacement of the premaxilla and maxilla of the
      experimental animals was altered significantly in the superior direction, as
      expected from previous studies on monkeys. Changes in condylar morphology were
      also found, and the jaw joint discs were remodeled. Contrary to primate findings,
      however, anterior growth of the premaxillary, maxillary and zygomatic bones was
      greatly reduced. This difference in response between monkeys and pigs may be due
      to the way the bite block altered the load on the zygomatico-maxillary suture.

PMID- 8739767
TI  - Fiber type composition of morphologic regions in the macaque multitendoned finger
      muscles.
AB  - The extrinsic multitendoned finger muscles seem likely to contain distinct
      neuromuscular compartments that can act as independent functional subdivisions
      serving different fingers. Little evidence of such subdivisions is available,
      however. Regional specialization of histochemical fiber type composition has been
      described in a number of monotendoned muscles, and in some muscles different
      neuromuscular compartments have been shown to have different fiber type
      proportions. Therefore, we examined the fiber type composition of morphologically
      defined regions in the macaque multitendoned finger muscles. Although some trends
      were noted, none of the five multitendoned finger muscles showed significant
      regional differences in fiber type composition. Nor were differences found
      between muscles of the flexor group or between muscles of the extensor group.
      Comparing flexors and extensors revealed a slightly but significantly lower
      proportion of type I fibers in the flexors. We conclude that unlike certain
      monotendoned wrist muscles (such as FCU), the multitendoned muscles that flex and
      extend macaque fingers have minimal histochemical specialization.

PMID- 8739768
TI  - Three-dimensional structure of the sarcoplasmic reticulum at the neuromuscular
      junctions of the rat diaphragm.
AB  - The three-dimensional structure of the sarcoplasmic reticulum at the
      neuromuscular junctions of the rat diaphragm was investigated by means of a
      selective staining technique allowing studies of thick sections combined with
      stereoscopic observations. The sarcoplasmic reticulum (SR) has different
      organizations related to the various regions of the postsynaptic cytoplasm. At
      the base of the membranous folds or deep region, flattened cisternae are smaller
      and connected by numerous anastomosed tubules. In the mitochondria-rich region,
      the SR is composed of large flattened cisternae. Between the postsynaptic folds,
      the SR is formed of poorly anastomosed thin tubes which give rise to single
      tubules running close to the plasmalemma. The SR is also associated with the
      Golgi apparatus present in the deeper mitochondria-rich region. This specific
      organization of the SR in the postsynaptic cytoplasm of the neuromuscular
      junctions might, like the Golgi apparatus, be involved in the synthesis of some
      specific proteins, enzymes and receptors.

PMID- 8739769
TI  - Presence of calmodulin and NADPH-diaphorase activity but not of neuronal nitric
      oxide synthase in the subcommissural organ of the Mongolian gerbil.
AB  - The subcommissural organ (SCO) and the ventricular ependyma of the third
      ventricle of the Mongolian gerbil (Meriones unguiculatus) exhibit a highly
      positive histochemical reaction to NADPH-diaphorase and a considerable
      immunocytochemical expression of calmodulin. The SCO, however, does not display
      an immunocytochemical response to the neuronal isoform of nitric oxide synthase
      (NOS) whereas it was demonstrated in the ventricular ependyma. Since the NADPH
      diaphorase, which detects all isoforms of NOS, was clearly positive at the level
      of the SCO, the obtained results suggest that the SCO of the Mongolian gerbil
      produces nitric oxide but contains a NOS whose antigenic specificity differs from
      that of the neuronal isoform of this enzyme.

PMID- 8739770
TI  - Biphalangeal and triphalangeal toes in the evolution of the human foot.
AB  - The number of phalanges of the human toes was investigated in a series of 2,550
      radiographs. Classical triphalangia of the lateral toes (2-5) was observed in
      1,440 cases (56.47%). Biphalangeal disposition was observed for the 5th toe in
      1,110 cases (41.02%), for the 4th toe in 64 cases (2.51%), for the 3rd toe in 5
      cases (0.20%), and for the 2nd toe in 3 cases (0.12%). The frequency of
      biphalangia of a given toe was not independent of the others. Biphalangeal toes
      result primarily from the absence of development of the distal interphalangeal
      joint. Biphalangia of the toes is a derived character which is restricted, within
      primates, to the human species, in relation to the reduction of the toes in
      adaptation to bipedalism.

PMID- 8739771
TI  - Mutations of the thyroxine-binding globulin gene in Japanese.

PMID- 8739772
TI  - Rising prevalence of neurodegenerative diseases worldwide.

PMID- 8739773
TI  - Comments on different states of secretory autonomy of juxtaglomerular cell tumors
      of the kidney.

PMID- 8739774
TI  - Chromosome 16 inversion in acute myelogenous leukemias with bone marrow
      eosinophilia.

PMID- 8739775
TI  - Molecular biology of heart disease. Synopsis of the pathophysiological basis of
      cardiac hypertrophy, familial hypertrophic cardiomyopathy, long QT syndrome and
      Marfan syndrome.
AB  - Cardiovascular disease is the one of the most important causes of morbidity and
      mortality throughout the world. Despite the advances in technology in the
      surgical or interventional therapies, complete understanding of the causes and
      pathogenesis of the disease is imperative to develop specific therapeutic
      modalities tailored to those underlying abnormalities. Recent progress in
      molecular biology has markedly expanded our knowledge of the pathophysiology of
      many cardiovascular diseases. Such an evolution of the basis science of
      cardiovascular medicine will allow the physician to treat the primary dysfunction
      rather than treating secondary manifestations. This review is designed to
      illustrate the impact of molecular biology on cardiovascular medicine with an
      emphasis on the pathogenesis of cardiac hypertrophy, and identification of the
      genes responsible for familial hypertrophic cardiomyopathy, long QT syndrome, and
      inherited vasculopathies such as Marfan syndrome.

PMID- 8739776
TI  - Regulation of pancreatic exocrine function in Otsuka Long-Evans Tokushima Fatty
      (OLETF) rats without gene expression of cholecystokinin-A receptor.
AB  - This work extends a recent observation that Otsuka Long-Evans Tokushima Fatty
      (OLETF) rats show a congenital defect of the cholecystokinin (CCK)-A receptor
      gene. Expression of CCK-A receptor mRNA in the pancreas, small intestine and
      brain were not detected in OLETF rats by the reverse transcriptase polymerase
      chain reaction. In vitro studies showed that the maximal effective concentrations
      of neuromedin C, acetylcholine and secretin for stimulation of amylase secretion
      were comparable in both strains, but that CCK-stimulated amylase secretion was
      observed only in Long-Evans Tokushima Otsuka (LETO) rats. Intracellular cytosolic
      Ca2+ movement stimulated by acetylcholine and neuromedin C was similar in both
      strains. In vivo studies showed that the pancreatic secretions in response to
      secretin and acetylcholine were not impaired in OLETF rats. However, protein
      responses to neuromedin C and 2-deoxy-D-glucose were impaired in OLETF rats. The
      findings suggest that pancreatic exocrine functions in OLETF rats are regulated
      by all neural and peptidergic agents except CCK.

PMID- 8739777
TI  - Acute hypoxic pulmonary vascular response does not accompany plasma endothelin-1
      elevation in subjects susceptible to high altitude pulmonary edema.
AB  - We have previously shown that high altitude pulmonary edema-susceptible subjects
      (HAPE-S) have an accentuated pulmonary vascular response to hypoxia. In this
      study, we investigated the relationship between plasma endothelin-1 (ET-1) levels
      and the acute hypoxic pulmonary vascular response in HAPE-S and control subjects.
      In six HAPE-S and seven healthy subjects, we evaluated acceleration time/right
      ventricular ejection time (AcT/RVET) using Doppler echocardiography, and measured
      plasma ET-1 levels by radioimmunoassay (RIA) before and after 5 minutes of
      breathing 10% oxygen. The HAPE-S showed a significantly increased pulmonary
      vascular response to hypoxia compared with healthy subjects. However, no
      statistically significant changes of plasma ET-1 levels were observed before and
      after hypoxia in both groups. We conclude that the increased pulmonary vascular
      response to acute hypoxia in HAPE-S may not be related to ET-1 release.

PMID- 8739778
TI  - Electrocardiographic diagnosis of left circumflex artery occlusion and the
      occlusion site.
AB  - In patients with a posteroinferior acute myocardial infarction and both ST
      depression (in lead V1 or V2) and ST elevation in the inferior leads, it is
      difficult to differentiate a left circumflex artery occlusion from a right
      coronary artery occlusion. Furthermore, there is no useful method to identify the
      obstruction site in the left circumflex artery. In a study of 52 patients with
      single-vessel left circumflex artery disease, ST elevation in V6 was found to be
      a useful indicator for left circumflex artery occlusion in such patients.
      Furthermore, the sum of the ST changes in leads a VF and V2 is useful for
      identifying the occluded site in the left circumflex artery.

PMID- 8739779
TI  - Mass screening for complete deficiency of thyroxine-binding globulin in adult
      Japanese by comprehensive health examination.
AB  - The incidence of complete thyroxine-binding globulin (TBG) deficiency (TBG-CD)
      was determined for a Japanese population from a comprehensive health examination,
      in which a T3 resin uptake test of the upper 5% (78 subjects from among 1,589
      men) was the screening line for TBG-CD. Further analysis of the known mutation in
      TBG-CD gene of the Japanese population (reported as TBG-CDJ with codon 352
      deletion) was performed on 72 subjects, and three were found to have TBG-CDJ, two
      of whom were siblings. Only those three subjects had a serum TBG concentration of
      less than 5 mg/l. The six subjects for whom the DNA analysis was not performed,
      did not have a serum TBG level of less than 5 mg/l. From these findings, the gene
      frequency of TBG-CDJ was calculated to be 0.13%. The incidence of TBG-CDJ in the
      total Japanese population is suggested to be 0.09%.

PMID- 8739780
TI  - Clinical significance of the increased peak levels of exhaled nitric oxide in
      patients with bronchial asthma.
AB  - We measured exhaled nitric oxide (NO) with a chemiluminescence method to
      elucidate the clinical significance of the increased concentration of exhaled NO
      in patients with bronchial asthma. Exhaled NO was measured in 25 patients with
      bronchial asthma and in 10 healthy control subjects. The concentration of exhaled
      NO in asthmatics was significantly higher than in the controls (250.4 +/-
      30.4,59.9 +/- 9.6 ppb, respectively, p < 0.01). Symptomatic patients (unstable
      asthmatics) had a higher exhaled NO concentration than did the asymptomatic
      patients (stable asthmatics) (384.2 +/- 32.5,143.6 +/- 18.8 ppb, respectively, p
      < 0.01). The exhaled NO concentration was significantly correlated with the peak
      expiratory flow rate (r = 0.671, p < 0.01) and eosinophil ratio in induced sputum
      (r = 0.772, p < 0.05), but it was not correlated with the parameters of bronchial
      hyperactivity (Dmin and PD35 Grs). We conclude that the increased concentration
      of exhaled NO in patients with bronchial asthma reflects the state of airway
      inflammation, and we suggest that the measurement of exhaled NO is a useful, non
      invasive and simple method for the management of bronchial asthma.

PMID- 8739781
TI  - Prevalence of Parkinson's disease in Hokkaido, the northernmost island of Japan.
AB  - The prevalence of Parkinson's disease (PD) was investigated in Hokkaido, the
      northernmost island of Japan. A pilot case-finding study was carried out to
      estimate the prevalence in the entire island of Hokkaido (population = 5,643,647)
      initially, then we surveyed the prevalence at one of the smaller cities,
      Iwamizawa City (population = 80,417). We ascertained 5,342 cases with PD in
      Hokkaido and 77 cases in Iwamizawa City, estimating the crude prevalence of
      94.7/100,000 in Hokkaido (June 30, 1993) and 95.8/100,000 in Iwamizawa City
      (April 1, 1994), respectively. We calculated that the crude prevalence rate of PD
      in Japan in currently close to 100/100,000, but the age-adjusted prevalence is
      still low, compared with those in Europe and North America.

PMID- 8739782
TI  - A rare case of ectopic antidiuretic hormone-producing pancreatic adenocarcinoma:
      new diagnostic approach.
AB  - We describe a 73-year old man with the syndrome of inappropriate antidiuretic
      hormone secretion (SIADH) due to an ectopic ADH-producing pancreatic
      adenocarcinoma. His laboratory findings showed marked hyponatremia, and the water
      load test showed uncontrolled ADH secretion. The imaging studies revealed
      pancreatic body cancer. Histological examination revealed an adenocarcinoma of
      the pancreas, which was positive for ADH immuno-staining. The ADH in the tumor
      extract was 53.3 pg/g wet weight. In attempt to diagnose ADH-production from the
      tumor, the ADH in his pancreatic juice was measured and found to be 2.1 pg/ml. We
      conclude that it is valid to measure the ADH in pancreatic juice to diagnose
      ectopic ADH production by tumors.

PMID- 8739783
TI  - Multiple endocrine neoplasia type 1 associated with spinal ependymoma.
AB  - A 51-year-old man was hospitalized with a gait disturbance and hypoesthesia below
      the level of his chest. These symptoms were due to a spinal tumor which was
      surgically resected and identified as an ependymoma. Additionally, the patient
      had hypercalcemia and a family history of insulinoma. An endocrine evaluation
      revealed parathyroid hyperplasia and a pancreatic islet cell tumor. Magnetic
      resonance imaging disclosed a pituitary microadenoma. He was diagnosed with
      spinal ependymoma and multiple endocrine neoplasia type 1 (MEN 1). A review of
      the literature revealed that chromosome 11q13 abnormalities have been reported in
      both ependymoma and MEN 1. We discuss the pathogenesis of these diseases.

PMID- 8739784
TI  - Syndrome of inappropriate secretion of antidiuretic hormone following intra
      thoracic cisplatin.
AB  - A case of malignant thymoma with pure red cell aplasia (PRCA) complicated by
      syndrome of inappropriate secretion of antidiuretic hormone (SIADH) following
      intrathoracic cisdichlorodiammine platinum (CDDP) administration is reported. A
      59-year-old Japanese woman who presented with severe general fatigue was
      diagnosed with PRCA associated with a thymoma, based on the findings of a bone
      marrow biopsy, computed tomography of the chest, and the existence of anti
      acetylcholine receptor antibodies. She underwent a thymectomy after frequent
      blood transfusions. This was followed by intrathoracic CDDP administration,
      because of pleural dissemination. Nine days following chemotherapy, her serum
      sodium concentration was found to be 104mM, while her consciousness was drowsy
      with severe fatigue and vomiting. This hyponatremic state was diagnosed as SIADH
      induced by CDDP infusion into the thoracic space, based on the hypo-osmolality of
      her serum, the hyper-osmolality of her urine, and an inappropriate level of
      plasma vasopressin.

PMID- 8739785
TI  - A very small juxtaglomerular cell tumor preoperatively identified by magnetic
      resonance imaging.
AB  - We describe a 31-year-old man. Although the plasma renin activity (PRA) and
      plasma aldosterone concentration (PAC) were elevated, computed tomography and
      rapid sequence pyelography disclosed no abnormality. However, based on the
      findings of the small tumor (8 x 8 mm) in the kidney visualized by magnetic
      resonance imaging (MRI) and excessive PRA in the right renal vein, tumor
      resection was performed. The positive immunohistochemical staining of renin and
      the visualization of renin mRNA by in situ hybridization provided evidence
      supporting the diagnosis of juxtaglomerular cell tumor. Blood pressure, PRA, and
      PAC were normalized after the surgery. The observations suggest that MRI is a
      powerful diagnostic procedure in small juxtaglomerular cell tumor.

PMID- 8739786
TI  - Hypersensitivity pneumonitis induced by spores of Pholiota nameko.
AB  - A 42-year-old man experienced recurrent episodes of nonproductive cough, fever,
      and dyspnea on exertion. He had worked as a mushroom farmer for 10 years. The
      diagnosis of hypersensitivity pneumonitis was confirmed immunologically by
      detecting a precipitin to spores of Pholiota nameko but not to other antigens.
      After separation from the antigen along with an addition of corticosteroid
      therapy, the symptoms, inflammatory findings and a reduced level of PaO2 quickly
      subsided.

PMID- 8739787
TI  - Human T-cell lymphotropic virus type I (HTLV-I) carrier with clinical
      manifestations characteristic of diffuse panbronchiolitis.
AB  - A 45-year-old male was referred due to prolonged productive cough. Despite the
      fact that bronchoalveolar lavage fluid suggested lymphocytic and neutrophilic
      alveolitis, the histologic diagnosis of his biopsied lung was diffuse
      panbronchiolitis-like lesion with infiltration of lymphocytes and plasma cells
      into respiratory bronchioles but few foamy cells. Serologic examination revealed
      that he was a carrier of human T-cell lymphotropic virus type I (HTLV-I).
      Together with uveitis and ulcerative colitis in his past history, the persistent
      respiratory symptoms of this patient can be attributed to non-neoplastic
      inflammation due to the chronic HTLV-I infection.

PMID- 8739788
TI  - An unusual case of brucellosis in Japan: difficulties in the differential
      diagnosis from pulmonary tuberculosis.
AB  - Human brucellosis is an imported zoonosis extremely uncommon in Japan.
      Brucellosis was found in a 38-year-old surgeon who had never been abroad; he
      developed intrapulmonary infiltrates and pleural thickening indistinguishable
      from pulmonary tuberculosis. Despite extensive antibiotic therapy for
      tuberculosis he developed systemic serositis. A culture of resected lung tissues
      grew CO2-required coccobacilli. Polymerase chain reaction test using a specific
      primer pair for Brucella abortus revealed that the isolated pathogen is highly
      homologous to B. abortus. We emphasize that undetermined cases of human
      brucellosis may be present in Japan.

PMID- 8739789
TI  - Varicella pneumonia in a healthy adult presenting with severe respiratory
      failure.
AB  - We describe a case of varicella pneumonia in a 24-year-old healthy man presenting
      with severe respiratory failure. A chest radiograph showed diffuse, bilateral
      airspace consolidation; additional complications included liver dysfunction and
      thrombocytopenia. However, treatment with intravenous acyclovir and gamma
      globulin improved his clinical symptoms and signs. A greater than four-fold
      change in paired titers of the varicella-zoster virus antibody was observed.
      Bronchoalveolar lavage performed during the recovery phase revealed increased
      total cell and lymphocyte counts and a decreased CD4:CD8 ratio of T lymphocytes.
      Transbronchial lung biopsy findings were compatible with a diagnosis of
      interstitial pneumonia.

PMID- 8739790
TI  - The effect of non-activated prothrombin complex concentrate (Proplex ST) on
      intraperitoneal hematoma in a hemophilia A patient with a factor VIII inhibitor.
AB  - A 28-year-old severe hemophiliac with a factor VIII inhibitor was admitted to our
      hospital with a massive and serious intraperitoneal hematoma. He was a high
      responder patient showing maximal serum inhibitor levels as high as 255 Bethesda
      Units/ml (BU/ml). He was successfully treated with "bypass therapy" using a
      prothrombin complex concentrate (PCC).

PMID- 8739791
TI  - Disseminated nontuberculous mycobacteriosis caused by mycobacterium kansasii in a
      patient with myelodysplastic syndrome.
AB  - A 38-year-old man with pancytopenia due to myelodysplastic syndrome exhibited
      persistent pyrexia and mediastinal lymphadenopathy. A biopsy specimen of the
      lymph nodes showed diffuse infiltration of epitheloid cells, including acid-fast
      bacilli identified as Mycobacterium kansasii. Cultures from gastric lavage and
      stool yielded M. kansasii, and granulomas were found in the bone marrow. A
      diagnosis of disseminated nontuberculous mycobacteriosis (DNTM) was established.
      The patient's condition improved after treatment with isoniazid, rifampicin,
      ethambutol and granulocyte colony-stimulating factor. Although DNTM due to M.
      kansasii is rare in Japan, it should be recognized as a possible cause of
      opportunistic infections.

PMID- 8739792
TI  - CBFB/MYH11 fusion transcripts in a case of acute myelogenous leukemia (M1) with
      partial deletion of the long arm of chromosome 16.
AB  - Pericentric inversion of chromosome 16 [inv(16)(p13q22)] is seen in patients with
      acute myelomonocytic leukemia with bone marrow eosinophilia. This inversion
      juxtaposes the MYH11 gene on p13 and the CBFB gene on q22, resulting in the
      formation of a chimeric mRNA transcript. We describe a patient with acute
      myelogenous leukemia (M1), with del(16)(q22), who expressed the chimeric
      transcript. Reverse transcriptase polymerase chain reaction and the sequencing of
      its product showed fusion of 5'CBFB at position 495 to 3'MYH11 at position 1201.
      To our knowledge, this is the first report of an AML (M1) case with del(16) and
      CBFB/MYH11 rearrangement.

PMID- 8739793
TI  - Lymphoproliferative disorder of granular lymphocytes (natural killer cell type)
      with interstitial pneumonia in a patient with familial pancytopenia.
AB  - A 50-year-old woman is presented here with natural killer (NK) cell type
      lymphoproliferative disorder of granular lymphocytes. She was admitted to the
      hospital because of dyspnea on exertion. Chest X-ray revealed bilateral reticular
      shadows. Open lung biopsy demonstrated usual interstitial pneumonia (UIP). Her
      white blood cell count was 3,900/mm3, of which 55% was large granular lymphocytes
      (LGLs). The LGLs were CD3- CD16+CD56+, and the clonality of them was not
      confirmed. Despite steroid therapy, she died from exacerbation of UIP complicated
      with opportunistic infection. The patient, her father and son had pancytopenia.
      Congenital immunological abnormality might cause both large granular
      lymphocytosis and UIP.

PMID- 8739794
TI  - Hyperlipidemia associated with multiple myeloma.
AB  - A 70-year-old woman with type IIb therapy-refractory hyperlipidemia was diagnosed
      as having IgA kappa type multiple myeloma. She had neither a family history nor
      any other disease known to accompany hyperlipidemia. The serum IgA concentration
      fell from 3.42 g/dl to 1.24 g/dl following chemotherapy with melphalan and
      prednisolone, and a concomitant decrease in both the serum cholesterol and
      triglyceride levels was observed. These serum lipids were positively correlated
      with the serum IgA concentration (p < 0.001) during the three cycles of
      chemotherapy. These findings suggest the involvement of the monoclonal protein of
      IgA in the development of hyperlipidemia in the present case.

PMID- 8739795
TI  - Bronchiolitis obliterans organizing pneumonia associated with systemic lupus
      erythematosus with antiphospholipid antibody.
AB  - Bronchiolitis obliterans organizing pneumonia (BOOP) is a pathologic entity
      characterized by the formation of fibrous tissue plugs within terminal
      bronchioles and alveolar ducts. Although BOOP has been associated with several
      connective tissue disorders, there are rare reports of BOOP in patients with
      systemic lupus erythematosus (SLE). We present a patient with SLE accompanying
      antiphospholipid antibody who developed recurrent respiratory symptoms and
      radiographic abnormalities. The diagnosis of BOOP was confirmed by transbronchial
      lung biopsy. This case suggests that not only SLE, but also the presence of
      antiphospholipid antibody, may be associated with the development of BOOP.

PMID- 8739796
TI  - Severe alpha-2 agonist withdrawal syndrome in diabetes mellitus.

PMID- 8739797
TI  - A negative test for antineutrophil cytoplasmic antibody does not necessarily
      exclude the diagnosis of Wegener's granulomatosis.

PMID- 8739798
TI  - A new quantitative RT-PCR assay for the vasoconstrictor endothelin.
AB  - Endothelin has been found to be the most powerful and important factor regulating
      vasoconstriction in normal and pathological conditions. Rapid degradation and
      very low concentrations make it difficult to use even very sensitive enzymatic or
      immunochemical assays for this oligopeptide. We have established a quantitative
      polymerase chain reaction (PCR) assay for the mRNA of endothelin-1 (ET-1), the
      best characterized of the three endothelin isoforms known so far. Using human
      umbilical vein endothelial cells as source for endothelin, the absolute number of
      ET-1 cDNA molecules serving as template for the amplification reaction can be
      calculated with the aid of an internal standard as competitor for the PCR
      primers, while relative amounts of ET-1 mRNA are estimated with a new solid-phase
      enzyme-linked immunosorbent assay for the PCR product of ET-1 and a
      constitutively expressed single copy gene product, beta-actin. The combination of
      these supplementary assay systems allows the analysis of endothelin-1 mRNA
      regulation on a very sensitive level.

PMID- 8739799
TI  - Hypovolemic shock and cardiac contractility: assessment by end-systolic pressure
      volume relations.
AB  - The end-systolic pressure-volume relation (ESPVR) is accepted as a load
      independent measure of cardiac contractility. Potential curvilinearity of the
      ESPVR, dependency on coronary perfusion pressure (CPP) and sensitivity to the
      type of loading intervention might limit its use in hemorrhagic shock. This study
      compared ESPVRs obtained by caval and aortic occlusion under physiological
      loading conditions at baseline with those obtained during hemorrhagic shock (mean
      arterial pressure 45 mmHg). The left ventricular (LV) pressure (tip manometer)
      and volume (conductance catheter) were measured in ten anesthetized pigs. ESPVRs
      were fitted to linear and quadratic models. Within end-systolic pressure (Pes)
      ranges obtained under baseline conditions, ESPVR displayed only minimal
      curvilinearity (second-order coefficient a < 0.007) and could be accurately
      described by a linear model. However, nonlinearity of ESPVRs obtained over wider
      load ranges is suggested by negative volume axis intercepts of the linear model.
      Steeper ESPVR with aortic than with caval occlusion (2.28 +/- 0.22 vs 3.41 +/-
      0.51 mmHg/ml, ns) could not be proven owing to the large interindividual variance
      of ESPVR slopes with both loading interventions. During shock the Pes range
      obtained by caval occlusion decreased to very low levels (from 49 +/- 2 to 34 +/-
      1 mmHg), ESPVR did not adequately fit either of the two models (mean R < 0.66),
      and critical reduction of CPP induced negative ESPVR slope in four of ten
      experiments. In contrast, aortic occlusion at shock resulted in linear ESPVR (R =
      0.927 +/- 0.029), Pes ranges (92 +/- 3 to 58 +/- 4 mmHg) comparable to the ones
      obtained by caval occlusion at control (113 +/- 5 to 73 +/- 6 mmHg), and steeper
      ESPVR than at control (3.41 +/- 0.51 to 7.38 +/- 1.0 mmHg/ml, P < 0.05).
      Interpretation of the increased ESPVR slope obtained with aortic occlusion as due
      to increased contractility in shock is, however, complicated by different Pes
      ranges. It is concluded that within Pes ranges obtained with caval or aortic
      occlusion in situ the ESPVR can be adequately fitted to a linear model. For
      assessment of the inotropic response to shock the ESPVR is of limited value
      because (1) caval occlusion is not suitable to generate ESPVR during shock, and
      (2) Pes ranges obtained with identical loading interventions differ greatly
      between baseline and shock and, therefore, apparent ESPVR changes are influenced
      by the potential nonlinearity of the ESPVR. Combining caval occlusion at baseline
      with aortic occlusion at shock would result in comparable Pes ranges.
      Interpretation of results is, however, complicated by diverging effects of the
      different loading interventions on the shape and slope of the ESPVR.

PMID- 8739800
TI  - Rat model of mild stenosis of the common bile duct.
AB  - Several techniques for developing incomplete obstruction of the common bile duct
      have been described but none of them properly represents a compression or
      constriction of the bile duct. In this study, a mild stenosis of the common bile
      duct was achieved in the rat by means of a double ligature including a cannula
      that could be easily slipped out of the ligatures. Sham-operated rats were used
      as controls. The studies, performed 7-10 days postoperatively, indicated that in
      ligated rats a duct constriction was produced, made evident by an increase of the
      biliary pressure, an upstream dilatation of the bile duct, an increase of the
      liver volume constituted by portal tracts, and ductular proliferation. Serum
      parameters were practically similar in ligated and control rats, except for a
      slight increase in serum bilirubin. Following intravenous injection of sodium
      taurocholate there were rapid increases of bile flow and bile salt output in both
      groups, but choleresis induced by sodium taurocholate was higher in ligated rats
      than in controls. The clearances of [14C]erythritol and [14C]sucrose suggested
      that ductular water contributing to bile flow and changes in biliary permeability
      were not involved in ligated rats. The limited repercussion of humoral effects
      and hepatic behaviour seen in ligated rats despite the morphological alterations
      induced make the mild stenosis of the bile duct a good model for the study of
      early stages of compression or constriction of the biliary tract.

PMID- 8739801
TI  - Manipulation of the size and clone of an intra-abdominal abscess in rats.
AB  - A rat grading model of chronic sepsis was developed by inoculation of a small
      (0.8 ml) or a large (1.5 ml) fecal pellet consisting of sterile rat feces, agar
      and a known number and strain of bacteria. A uniform spherical abscess containing
      Escherichia coli and Bacteroides fragilis was formed in 100% of the animals that
      survived the initial peritonitis stage. The effects of a large biclonal abscess
      were compared with those of a small abscess and of a sham operation. The
      peritonitis stage with high mortality was followed by an abscess stage. In rats
      with a large abscess, net body weight did not increase and there was 16%
      mortality during the abscess stage. On the 7th day, severe hepatic energy
      deficiency and lactic acidosis occurred in the septic liver with B. fragilis
      bacteremia. Rats with small abscesses showed mild metabolic disturbances with no
      mortality. Standardization of rat models with chronic graded septic abscess is
      possible by controlling the size of the fecal pellet and the species and number
      of inoculated bacteria.

PMID- 8739802
TI  - Chemotactic response of human alveolar macrophages and blood monocytes elicited
      by exposure to sulfur dioxide.
AB  - An experimental study was undertaken to investigate the in vitro effect of sulfur
      dioxide on the chemotactic activity of alveolar macrophages (AM) and blood
      monocytes (BM). The cells were placed on a polycarbonate membrane and exposed to
      SO2 0.5, 1.5 and 2.5 ppm for 15 min. Control experiments were performed with
      exposure of the cells to synthetic air with 5% CO2. After gas exposure the cells
      were incubated with the chemotactic active agent C5a in 5% carbon dioxide (CO2)
      at 37 degrees C for 60 min. The numbers of AM and BM passing actively through the
      membrane were quantified using light microscopy. Our results show a dose
      dependent reduction in the migration rate of cells under SO2 exposure. SO2 0.5
      ppm induced a 29% and SO2 2.5 ppm a 53% decrease in migration of AM compared with
      the control exposure to synthetic air (P < 0.01). Identical experiments with BM
      resulted in a decrease in migration of up to 57% (P < 0.01). At SO2
      concentrations of up to 2.5 ppm no significant cytotoxic effects were observed
      for AM or BM. The data demonstrate that exposure to SO2 may reduce the
      chemotactic activity of AM and BM. Our results further suggest that the decrease
      in cell migration induced by SO2 is due to changes in chemotactic mechanisms and
      not to cell death.

PMID- 8739804
TI  - Clinical trials: relevance of correlation between treatment responses.
AB  - OBJECTIVE: Trials that do not allow rejection of the null hypothesis of no
      treatment effect may have had an inappropriate design. Trials are virtually never
      assessed for correlation between responses to different treatment modalities.
      METHODS: Using a hypothetical example and several published studies we examine
      the influence of correlation levels between treatment modalities on the
      sensitivity of testing. RESULTS: The level of correlation between responses to
      different treatment modalities is a major determinant of the sensitivity both of
      crossover and parallel group clinical trials. CONCLUSIONS: It is very relevant to
      assess a priori correlation levels between responses to the different treatment
      modalities of a trial. If a negative correlation is anticipated, a crossover
      design is likely to lack sensitivity. If a positive correlation is anticipated a
      parallel-group design seems less appropriate, because it would lack the extra
      sensitivity of accounting for the positive correlation. Both designs would seem
      suitable for approximately zero correlations (e.g. comparison vs baseline or vs
      placebo under the assumption that the number of placebo responders is negligible.

PMID- 8739803
TI  - Leu-enkephalin enhances interferon secretion in mice.
AB  - This work has explored the possibility that alterations of NK activity induced by
      the opioid pentapeptide leu-enkephalin (LENK) may reflect the alterations in
      secretion of IFN, an important regulator of NK activity. The NK activity in the
      spleen of mice was determined in parallel with the plasma IFN level 24 and 48 h
      after an i.p. injection of LENK (10 mg/kg). A known inducer of IFN secretion,
      polyinosinic-polycytidylic acid (poly-IC), was also used. LENK injection
      significantly increased basal IFN secretion 24 and 48 h later. The level was
      comparable to that induced by poly-IC. However, LENK was not able to augment the
      poly-IC-increased IFN level. The increase of IFN at 48 h coincided with a mild
      enhancement of NK activity in the spleens, but 24 h after LENK injection, the
      increased IFN level in plasma was associated with a significant drop of splenic
      NK activity. LENK did not affect the NK activity stimulated with poly-IC.
      Naloxone (20 mg/kg), an opioid receptor-blocking agent, only partly diminished
      the LENK-induced IFN secretion. However, naloxone itself increased the plasma IFN
      level. These data indicate that the immunomodulatory effects of the opioid
      peptide LENK in vivo are associated with alterations of IFN secretion.

PMID- 8739805
TI  - Time course of physical and psychological responses to selegiline monotherapy in
      newly diagnosed, idiopathic parkinsonism.
AB  - RATIONALE: Poor specificity of face-value endpoints and the poor sensitivity of
      gross clinical examination may have militated against demonstrating prophylaxis
      by selegiline. METHODS: Objective measures of the four cardinal signs were used
      as primary outcome criteria in a randomised, double-blind, placebo-controlled,
      parallel group study of selegiline monotherapy in 25 newly diagnosed elderly
      sufferers from idiopathic parkinsonism, stratified for sex and Hoehn and Yahr
      functional staging. RESULTS: There was a significant interaction between time and
      nature of treatment with respect to rigidity. The effect of time during active
      treatment was highly significant: rigidity decreased by 1.3% per week. The
      worsening of rigidity on placebo was not statistically significant. Neuronal
      rescue is a possible explanation for the long term, progressive improvement
      produced by selegiline. No significant treatment effect was seen on the other
      cardinal signs. However, there was a significant quadratic time trend for arousal
      on active treatment suggesting tolerance to this effect. CONCLUSION: The
      difference in time course between the psychostimulant and physical effects
      suggests more than one mode of action.

PMID- 8739806
TI  - Use of benzodiazepines in the Italian general population: prevalence, pattern of
      use and risk factors for use.
AB  - This study was conducted to determine the prevalence and profile of use of
      benzodiazepines in the Italian population and risk factors for use. Between
      November 1992 and February 1993, 62 general practitioners submitted a validated
      self-administered questionnaire on health status and drug use to a randomised
      sample of 3100 subjects ( > or = 18 years of age, stratified by sex and age), of
      whom 2803 responded (response, rate 90.4%). Main outcome measures were point
      estimate (past-week) of all the drugs taken by each individual, dosage and length
      of use and source of the prescription. The overall past-week prevalence of use of
      benzodiazepines was 8.6% (5.0% males and 11.8% females). In the elderly ( > or =
      65 years) 18.8% reported current use (9.0% males and 24.7% females). Fifty-six
      per cent of the persons exposed to a benzodiazepine were chronic users (daily,
      for more than 6 months), and 70.1% in subjects > or = 65 years. The average daily
      dose taken was relatively low: 61% of short-term users and 51% of chronic users
      used less than half a defined daily dose (DDD). Female sex, older age,
      unemployment and retirement were independently associated with the use of
      benzodiazepines. Benzodiazepine use in Italy appeared to be relatively high
      (about 9% of subjects reported current use 57% of whom were chronic users). Women
      were prescribed a benzodiazepine twice as often as men and one out of four
      elderly women was on treatment. Although the average dosage used was rather low,
      the high prevalence and the elevated proportion of chronic users should encourage
      drug information campaigns and educational interventions to promote a more
      conservative use of these drugs especially in the elderly.

PMID- 8739807
TI  - Comparison of dose standard units for drug utilisation studies.
AB  - OBJECTIVE: As employment of different dose standards would be impractical and
      confusing, the aim of this article is to compare the define daily dose (DDD) with
      some more recently proposed standards, namely, the minimum marketed dose (MMD),
      the equipotential dose (ED), the average daily dose (ADD), and the non-standard
      prescribed daily dose (PDD). METHODS: Literature review, critical comparative
      analysis. RESULTS: The DDD, defined by an independent scientific committee
      assisting the WHO Collaborating Centre for Drugs Statistics Methodology, has been
      employed in a large number of national and international comparative studies at
      the population level, usually as number of DDDs per 1000 inhabitants per day.
      However, the DDD can also be used at the individual level. The PDD, not being a
      standard unit, can be appropriately used in a second step to explain differences
      detected by the DDD methodology. CONCLUSIONS: A globally accepted dose standard
      unit is important in drug utilisation studies, particularly if different
      investigations are to be compared. None of the alternatives seemed to offer any
      advantage over the DDD. Hence there is reason to advocate use of the DDD as the
      sole standard dose unit in all pharmacoepidemiologic studies.

PMID- 8739808
TI  - Xamoterol improves right ventricular systolic and diastolic function in pulmonary
      heart disease.
AB  - OBJECTIVE: Abnormal right ventricular function in patients with pulmonary heart
      disease (PHD) may contribute to their reduced exercise capacity. We have
      evaluated the effect of subacute dosing with xamoterol, a beta-1 adrenoreceptor
      partial agonist with inotropic properties, on right ventricular function in
      patients with PHD. PATIENTS: Twelve patients with advanced chronic obstructive
      pulmonary disease and clinical evidence of PHD received xamoterol 200 mg twice
      daily or placebo for 7 days in a randomised double-blind crossover study. Right
      heart krypton-81m radionuclide ventriculography was used to derive right
      ventricular ejection fraction (RVEF) both at rest and during submaximal exercise,
      and indices of right ventricular systolic and diastolic function at rest.
      RESULTS: During treatment with placebo, mean RVEF was 0.53 at rest and was
      unchanged during exercise. After xamoterol, mean RVEF was 0.55 at rest and
      increased to 0.59 during exercise. Xamoterol increased right ventricular peak
      ejection rate from 3.04 to 3.45 EDV.s-1 and mean early diastolic filling rate
      from 1.00 to 1.20 EDV.s-1. CONCLUSION: Subacute treatment with xamoterol in
      patients with PHD improves right ventricular systolic and diastolic function at
      rest and results in a favourable augmentation in right ventricular function
      during submaximal exercise.

PMID- 8739809
TI  - Influence of age on venodilator effect of isoproterenol and amrinone.
AB  - OBJECTIVE: To investigate the influence of age on the venodilator effect of
      isoproterenol, a beta-adrenoceptor agonist, and amrinone, a selective
      phosphodiesterase (PDE) III inhibitor, in human subjects. METHODS: In eight young
      and eight elderly male subjects, the drugs were infused into a dorsal hand vein
      preconstricted with phenylephrine and its diameter was measured using a linear
      variable differential transformer. RESULTS: The maximum venodilation (Emax)
      induced by isoproterenol was significantly smaller and the infusion rate of
      isoproterenol required to induce 50% of maximum venodilation (ED50) was
      significantly larger in the elderly than in the young subjects [Emax: 29.8 vs
      95.1%, ED50: 97.3 vs 51.6 ng.min-1]. A significant age-related change in Emax or
      ED50 was not observed for amrinone (Emax: 95.8 vs 100.8%, ED50: 40.1 vs 31.6
      micrograms.min-1). CONCLUSION: The data show that the venodilator effect of
      amrinone is not influenced by age. As amrinone increases cyclic AMP by inhibition
      of PDE III, it is suggested that the action of cyclic AMP is not altered by age.
      The decreased effect of isoproterenol might be caused by reduced production of
      cyclic AMP in elderly subjects.

PMID- 8739810
TI  - The effect of aging on the pharmacokinetics and pharmacodynamics of prazosin.
AB  - OBJECTIVE: The effect of age on the pharmacokinetics and pharmacodynamics of
      prazosin (alpha 1 adrenoceptor blocker) was studied in 20 healthy volunteers.
      PATIENTS: Ten elderly (61-81 y) and ten young (23-28 y) subjects were studied.
      All subjects received 1 mg of prazosin orally in a fasting state. Serial blood
      samples were collected for calculation of oral pharmacokinetics, and blood
      pressure and pulse rate were measured during blood collection. Subjects remained
      supine and fasting for the first three hours post drug administration, after
      which they were allowed to ambulate and eat. RESULTS: The oral pharmacokinetics
      of prazosin were not different in the two age groups. The serum t1/2 in the
      elderly was 210 min while in the young group was 139 min. The AUC(zero)-infinity
      in the two groups was not different. The Cmax was identical in the two groups,
      and the time to Cmax was 84 min in the elderly and 114 min in the young subjects.
      Protein binding was 93.4% in the elderly and 93.5% in the young subjects and the
      serum alpha 1 acid glycoprotein concentration was not different in the two groups
      of subjects. Even though the pharmacokinetics of prazosin were unchanged by age,
      the haemodynamic effects of the drug were greater in the elderly. The fall in
      systolic blood pressure and mean blood pressure was significantly greater in the
      elderly group at multiple time points after drug administration while the change
      in diastolic blood pressure was equivalent in the two age groups. Despite a
      greater decrease in mean blood pressure in the elderly, the compensatory increase
      in heart rate was similar in the two age groups suggesting a difference in the
      baroreceptor reflex in the two age groups. CONCLUSION: The results of this study
      demonstrate that age does not alter the pharmacokinetics of oral prazosin, but
      the pharmacodynamic response at equivalent plasma prazosin concentration is
      greater in the elderly.

PMID- 8739811
TI  - Multiple-dose clinical pharmacology of the catechol-O-methyl-transferase
      inhibitor tolcapone in elderly subjects.
AB  - OBJECTIVE: The purpose of this study was to assess the multiple-dose clinical
      pharmacology of tolcapone, a novel catechol-O-methyltransferase (COMT) inhibitor,
      in elderly subjects. METHODS: The drug was administered orally t.i.d. for 7 days
      to four sequential groups of eight elderly subjects (gender ratio 1:1) at doses
      of 100, 200, 400 and 800 mg in a double-blind, randomised, placebo-controlled,
      ascending-multiple-dose design. On days 2 and 7, a single dose of
      levodopa/benserazide 100/25 mg was given 1 h after the first intake of tolcapone.
      Plasma concentrations of tolcapone; its metabolite 3-O-methyltolcapone, levodopa
      and 3-O-methyldopa were determined during the course of the study in conjunction
      with COMT activity in erythrocytes. RESULTS: Tolcapone was well tolerated at all
      dose levels, with a slight increase in gastrointestinal adverse events in females
      at higher doses. The drug was rapidly absorbed and eliminated and showed no
      changes in pharmacokinetics with time during multiple doses of 100 and 200 mg
      t.i.d. At doses of 400 and 800 mg t.i.d., tolcapone accumulated moderately as
      reflected in increased Cmax and AUC values. Despite the long halflife of 3-O
      methyltolcapone (39 h), only minor accumulation occurred due to suppression of
      its formation by tolcapone. The pharmacodynamics of tolcapone did not change
      during the week of treatment as reflected in inhibition of COMT activity in
      erythrocytes, the derived parameters of the plasma concentration-effect
      relationship (inhibitory Emax model with constant EC50 values) and the effect on
      levodopa pharmacokinetics (1.6 to 2.5-fold increase in bioavailability). This
      suggests the absence of tolerance development and the insignificance of the
      altered pharmacokinetics at 400 and 800 mg t.i.d. with regard to the
      pharmacodynamics. CONCLUSION: The results of this study offer promising
      perspectives for the application of tolcapone as adjunct therapy to levodopa in
      the treatment of Parkinson's disease.

PMID- 8739812
TI  - A comparison of the pharmacokinetics and pharmacodynamics of cilazapril between
      Chinese and Caucasian healthy, normotensive volunteers.
AB  - METHODS: The pharmacokinetics and pharmacodynamics of the angiotensin converting
      enzyme (ACE) inhibitor cilazapril were studied in 12 Chinese and 13 Caucasian,
      healthy, normotensive volunteers on their normal diet. Cilazapril was given
      orally as a single 2.5 mg capsule. Plasma was sampled for assay of the active
      metabolite, cilazaprilat, plasma renin activity (PRA), aldosterone, angiotensin I
      (AI) and ACE-activity. Plasma concentrations of the active drug were measured by
      radioimmunoassay. Blood pressure and heart rate were measured at regular
      intervals. RESULTS: The pharmacokinetic parameters of cilazaprilat were similar
      in the two ethnic groups. No significant difference in plasma concentrations was
      found at any of the time points. However, the weight-adjusted plasma clearance
      was significantly higher in the Chinese group, which is compatible with their
      lower body weight. The effects on plasma hormones were also comparable, although
      there was a somewhat greater rise in PRA and greater fall in aldosterone levels
      in Chinese than in Caucasians. The effect of cilazapril on blood pressure and
      heart rate was greater than was previously reported in healthy volunteers.
      Systolic (SBP) and diastolic (DBP) blood pressure were significantly reduced in
      both groups, but there was a more prolonged reduction in DBP in Caucasians. In
      addition, heart rate (HR) was significantly increased from baseline from 5 h
      onwards in Chinese subjects and significantly higher in comparison with
      Caucasians at most time points from 1.5 h onwards. The pharmacokinetic parameters
      of cilazapril were essentially the same in healthy, normotensive Chinese and
      Caucasians. Cilazapril reduced blood pressure acutely in both groups, with good
      tolerance. The inhibition of ACE in relationship to time and the plasma
      concentrations of cilazaprilat were similar in the two groups, although the
      changes in PRA and aldosterone suggest an ethnic difference in the responses of
      the renin-angiotensin-aldosterone system.

PMID- 8739813
TI  - Comparison between a bid and a tid regimen: improved compliance with no improved
      antihypertensive effect. The EOL Research Group.
AB  - OBJECTIVES: To compare compliance with an antihypertensive treatment administered
      either twice daily or three times daily. The two formulations of the
      antihypertensive treatment used (nicardipine) "regular tablets" (t.d.) and "slow
      release tablets" (b.d.) are bioequivalent at the daily dosage used in the study.
      STUDY DESIGN: Open, controlled, parallel designed study with centralised,
      randomised allocation to the treatment groups: TID group: A nicardipine 20 mg
      tablet, three times daily for 3 months. BID group: A capsule of slow release (SR)
      nicardipine, 50 mg twice daily for 3 months. PATIENTS: 7274 hypertensive patients
      were investigated by 2.651 general practitioners. Compliance with the nicardipine
      was assessed by means of standardised interviews with the patients and by a
      questionnaire for the investigators. RESULTS: Compliance was slightly higher in
      the BID than in the TID group; 71.2% and 24.5% of patients in the first group
      declared their compliance was 100% and 80% compared to 82.3% and 15% in the
      second group. A statistically significant relationship was shown between
      compliance with nicardipine and the decrease in blood pressure after three months
      of therapy. However, no significant difference was noticed between the two groups
      of patients in the absolute decrease in blood pressure after the treatment
      period: 25.7/14.7 mm Hg in the TID group compared with 25.9/15.0 mm Hg in the BID
      group. CONCLUSIONS: A difference in compliance between the bioequivalent BID and
      TID formulations of the same active agent was shown in hypertensive patients.
      However, the difference was not large enough to lead to a difference either in
      the number of controlled patients or in the decrease in blood pressure. Reducing
      the number of daily doses does not automatically lead to greater efficacy of
      treatment.

PMID- 8739814
TI  - Metabolism of paracetamol in children with chronic liver disease.
AB  - OBJECTIVE: To study the metabolism of single doses of paracetamol in paediatric
      patients with chronic liver disease admitted to a hospital liver disease clinic.
      RESULTS: Thirteen paediatric patients, aged 7 months to 12 years, with chronic
      liver disease of varying severity were studied. In these children, paracetamol
      elimination half-life was negatively correlated with serum albumin and positively
      with prothrombin time, as previously reported in adults with liver disease. The
      rate constant of glucuronide formation was higher in the children with liver
      disease compared to the value reported in healthy children of similar ages. The
      rate constant of the formation of paracetamol sulphate was no different from that
      in normal children. The 36 h urinary paracetamol glucuronide to sulphate ratio
      was 1.4 (95% CI 0.8 to 1.7). This mean ratio was higher than in healthy children
      (0.81 and 0.75) but not significantly so, probably because of a Type 1 error due
      to the inevitable small sample size arising from the nature of the population
      being studied. CONCLUSION: The present study provides reassuring additional data
      to indicate that, at least for single doses, there is no cause for concern in the
      use of paracetamol in children with chronic liver disease.

PMID- 8739815
TI  - The effect of hypoxaemia on drug disposition in chronic respiratory failure.
AB  - OBJECTIVE: The influence of hypoxaemia on the disposition of two common drugs has
      been examined in ten adults with stable chronic respiratory failure. METHODS:
      There were two experimental periods in this cross-over study: during these
      periods supplemental oxygen was either withheld or administered to impose
      clinical hypoxaemia or maintain normoxaemia, respectively. Each participant
      received either oral (40 mg) or intravenous (20 mg) frusemide combined with oral
      paracetamol (500 mg) on consecutive days of the two experimental periods.
      RESULTS: The total (bound plus unbound) plasma clearance of frusemide during
      hypoxaemia (arterial oxygen tension, PaO2 < or = 50 Torr) was not significantly
      different from the value during normoxaemia (PaO2 > or = 60 Torr) [76.9 and 62.4
      ml.min-1]. The volume of distribution was not affected by acute hypoxaemia (121
      ml.kg-1 without and 109 ml.kg-1 with oxygen; P > 0.05). Renal and non-renal
      clearances of frusemide were similar during the period of hypoxaemia (31 and 38
      ml.min-1, respectively) compared to respective values during supplemental oxygen
      delivery (29 and 32 ml.min-1). The absolute bioavailability of frusemide during
      hypoxaemia (0.62) was not different to that obtained during normoxaemia (0.56).
      The combined sodium and potassium excretion rate (expressed as a function of the
      frusemide excretion rate) was not altered by changing the oxygen tension. The
      pharmacokinetics of paracetamol were unaffected by hypoxaemia.

PMID- 8739816
TI  - Influence of renal failure on cytochrome P450 activity in hypertensive patients
      using a "cocktail" of antipyrine and nifedipine.
AB  - OBJECTIVE: Two substrates were coadministered in a "cocktail" approach to
      evaluate the contribution of renal failure to drug oxidation. PATIENTS: Nineteen
      hypertensive patients, nine of them with chronic renal failure (CLCR 38.9 vs
      102.3 ml.min-1 1.73 m-2), were investigated after peroral administration of a
      combination of antipyrine (500 mg, in capsules) and nifedipine (10 mg, in Oxcord
      capsules) in the morning after an overnight fast. RESULTS: This "cocktail"
      approach made it possible to characterize in vivo the activities of different
      forms of cytochrome P450 in a single-study protocol using the total clearance of
      nifedipine and clearance for production of 3-hydroxymethylantipyrine (HMA), 4
      hydroxyantipyrine (OHA) and norantipyrine (NORA). With this "cocktail" approach
      (antipyrine plus nifedipine), we can suggest a selective effect on the activities
      of cytochrome P450 forms associated with the formation of dehydronifedipine (P450
      III A4) and of NORA in patients with mild renal failure under long-term
      antihypertensive therapy.

PMID- 8739817
TI  - Extrahepatic glucuronidation of propofol in man: possible contribution of gut
      wall and kidney.
AB  - OBJECTIVE: Results from clinical pharmacokinetic studies of propofol indicate
      that this i.v. anaesthetic agent may undergo significant extrahepatic
      glucuronidation. We have investigated whether glucuronidation of propofol takes
      place in the kidney and/or the gut wall. First, propofol concentrations were
      measured in arterial (radial artery) and portal venous blood of 12 cirrhotic
      patients with trans internal jugular porto-systemic shunting (TIPSS). RESULTS: In
      7 of the 12 patients arterial propofol concentrations were higher than portal
      venous concentrations. In the remaining patients, propofol concentrations were
      higher in the portal vein than the radial artery. Since an additional study in 5
      patients anaesthetized with propofol while undergoing cholecystectomy showed
      propofol and an acid-labile conjugate of it in bile, it is difficult to interpret
      the results in patients with TIPSS due to the possibility of enterohepatic
      cycling. Next, in vitro studies with human liver (n = 5), kidney (n = 5) and
      small intestinal (n = 5) microsomes showed that all three tissues were capable of
      forming propofol glucuronide. Vmax for propofol glucuronidation was approximately
      3 to 3.5 times higher in kidney (5.56 nmol.min-1.mg-1 protein) than liver (1.80
      nmol.min-1.mg-1 protein) and small intestine (1.61 nmol.min-1.mg-1 protein).
      CONCLUSION: Based on these in vitro results, it is concluded that extrahepatic
      glucuronidation in the small intestine and especially in the kidney may
      contribute to the overall glucuronidation of propofol in man.

PMID- 8739818
TI  - Effect of diprafenone on the pharmacokinetics of digoxin.
AB  - This study was conducted to investigate the effect of diprafenone on the steady
      state pharmacokinetics of digoxin. Twelve healthy men, all rapid hydroxylators of
      debrisoquine, received digoxin (0.5 mg per day over 7 days with a loading dose of
      2 x 1 mg) or digoxin and diprafenone (3 x 100 mg per day) in three different
      phases, without a wash-out period (phase 1, digoxin alone; phase 2, digoxin +
      diprafenone; phase 3, digoxin alone). Blood and urine samples were collected for
      pharmacokinetic analyses. Diprafenone caused a statistically significant increase
      in digoxin trough concentrations [1.4 (SD 0.2) vs 1.6 (0.3) ng.ml-1], AUC(zero)
      24 values [41 (7) vs 48 (9) ng.h.ml-1 and Css-max[3.9 (0.6) vs 5.5 (0.9) ng.ml
      1]. In all volunteers the parameters tended to return to the original values
      after administration of diprafenone was discontinued [1.4 (0.3) ng.ml-1, 39 (11)
      ng.h.ml-1, and 3.9 (1.1) ng.ml-1 for trough concentration, AUC(zero)-24 and Cmax
      respectively]. The mean relative magnitude of the increase in AUC(zero)-24 and
      trough concentration values corresponded to the mean relative decrease in the
      renal clearance of digoxin (in both cases approximately 20%). This suggests that
      the increase in AUC and Css was caused by reduced renal clearance of digoxin.

PMID- 8739819
TI  - Nefazodone pharmacokinetics: assessment of nonlinearity, intra-subject
      variability and time to attain steady-state plasma concentrations after dose
      escalation and de-escalation.
AB  - OBJECTIVE: The time required to reach steady-state plasma levels after an
      increase and a subsequent decrease in the dose of nefazodone, an antidepressant
      drug with nonlinear pharmacokinetics, was assessed in 24 healthy, male
      volunteers. METHODS: Each subject was administered 100 mg nefazodone
      hydrochloride b.i.d. (q 12 h) from study day 1 to 7, 200 mg b.i.d. from study day
      8 to 14 and 100 mg b.i.d. from study day 15 to 21. Trough (Cmin blood samples
      were obtained just prior to the morning dose on days 4-7, 11-14 and 16-21 to
      evaluate the attainment of steady state. Serial blood samples were collected for
      12 h after the morning dose on days 7, 14, 16, 18 and 21 for pharmacokinetic
      analysis of plasma levels of nefazodone (NEF) and its metabolites,
      hydroxynefazodone (HO-NEF), m-chlorophenylpiperazine (mCPP) and triazoledione
      (DIONE), which were determined by validated HPLC/UV assay methods. The Cmin
      results indicated that when nefazodone was administered at a dose of 100 mg
      b.i.d., steady-state plasma levels of parent compound and its metabolites were
      attained by the 4th day (i.e., after six doses) and when the dose was increased
      from 100 mg b.i.d. to 200 mg b.i.d. and then decreased back to 100 mg b.i.d., new
      steady-state plasma levels were also reached by the beginning of the 3rd or 4th
      day of each regimen. Consistent with the attainment of steady-state data, there
      were no statistically significant differences in Cmax or AUC values for
      nefazodone or its metabolites between study days 7, 18 and 21. Also consistent
      with the known nonlinear pharmacokinetics of nefazodone, the mean nefazodone
      steady-state Cmax and AUC values for the 200-mg dose were three fold and four
      fold greater, respectively, than those at the 100-mg dose level. Intrasubject
      variability (% cv) for NEF and its metabolites ranged from 13% to 24% for Cmax
      and AUC after 100 mg b.i.d.. Intersubject variability was considerably greater
      and ranged from 29% to 131% for Cmax and AUC after the same dose.

PMID- 8739820
TI  - Measurement of 5-fluorouracil in scalp hair: a possible index of patient
      compliance with oral adjuvant chemotherapy.
AB  - OBJECTIVE: Little is known about patient compliance with oral adjuvant
      chemotherapy. It is estimated to be poor especially in Japan, where it is still
      unusual for patients to be directly informed of their diagnosis of malignancy. 5
      Fluorouracil (5-FU) was measured in hair samples to assess patient exposure to 5
      FU, and its potential usefulness is discussed as an index of compliance with
      postoperative adjuvant chemotherapy. METHODS: Hair samples obtained from 55
      patients, who had received oral 5-FU (total dose 27-41 g) as postoperative
      adjuvant chemotherapy over a 6-month period, were used for the analysis of 5-FU.
      The drug was extracted from the hair using ethyl acetate, and its fluorescence
      derivatization was employed for measurement with HPLC. The detection limit of 5
      FU in hair was 0.01 ppm. RESULTS: In 22 out of 55 samples 5-FU content was under
      the detection limit, whereas in the remaining 33 samples the drug was detected in
      a range of 0.006-2.125 ng per hair strand; in addition, drug content showed a
      lognormal distribution. 5-FU was detected in the hair collected from those
      patients who were possibly compliant with the postoperative oral adjuvant
      chemotherapy. CONCLUSION: As many as 40% of the patients analysed were supposed
      to be much less compliant. Even in the possibly compliant patients, the degree of
      compliance with the therapy varied according to a log-normal distribution.

PMID- 8739821
TI  - Variability in the plasma protein binding of velnacrine (1-hydroxy tacrine
      hydrochloride). A potential agent for Alzheimer's disease.
AB  - OBJECTIVES: To quantify the protein binding of velnacrine in healthy individuals
      and investigate potential sources of variability. SETTING: Medical School Unit,
      Southmead Hospital, Bristol. SUBJECTS: Plasma samples were obtained from the
      following groups: a) 11 healthy volunteers aged 18 to 30 years; b) 10 healthy
      volunteers aged 73 to 87 years; c) 10 patients aged 65 to 85 years hospitalised
      for a variety of acute illnesses. METHODS: Aliquots of plasma from the above
      subjects were incubated with various concentrations of velnacrine, in the
      presence and absence of tacrine hydrochloride. Standard solutions of human serum
      albumin and alpha 1 acid glycoprotein were incubated with velnacrine. The degree
      of protein binding was determined using the Amicon centrifree micropartition
      system. RESULTS: 1) Over the range of concentrations from 10 to 320 ng.ml-1,
      there was a decrease in protein binding from 59.1 to 46.7%. 2) At 40 ng.ml-1 the
      plasma protein binding of velnacrine was 54.8% in the group a subjects, 51.9% in
      the group b subjects and 53.0% in the group c subjects (NS). 3) The mean total
      plasma protein concentration was significantly lower in the samples from elderly
      subjects. The mean albumin and alpha 1 acid glycoprotein concentrations were
      lower and higher respectively in patients with acute disease. 4) Velnacrine was
      shown to bind to both albumin and alpha 1-acid glycoprotein, but together they
      did not account for total binding. 5) The binding of velnacrine was significantly
      decreased from 59.3 to 43.9% in the presence of a therapeutic concentration (25
      ng.ml-1) of THA. There was no evidence that velnacrine displaced THA. CONCLUSION:
      Protein binding can be discounted as a major source of variation in the
      relationship between drug concentration and effect.

PMID- 8739822
TI  - Quinidine inhibits the 7-hydroxylation of chlorpromazine in extensive
      metabolisers of debrisoquine.
AB  - Quindine is a potent inhibitor of CYP2D6 (debrisoquine 4-hydroxylase). Its effect
      on the disposition of chlorpromazine was investigated in ten healthy volunteers
      using a randomised crossover design with two phases. A single oral dose of
      chlorpromazine hydrochloride (100 mg) was given with and without prior
      administration of quinidine bisulphate (250 mg). Chlorpromazine and seven of its
      metabolites were quantified in the 0- to 12-h urine while plasma concentrations
      of chlorpromazine and 7-hydroxychlorpromazine were measured over 48 h. All
      volunteers were phenotyped as extensive metabolisers with respect to CYP2D6 using
      the methoxyphenamine/O-desmethyl-methoxyphenamine metabolic ratio. Quinidine
      significantly decreased the urinary excretion of 7-hydroxylchlorpromazine 2.2
      fold. Moreover the urinary excretion of this metabolite correlated inversely (rs
      = -0.80) with the metabolic ratio. The urinary recoveries of chlorpromazine,
      chlorpromazine N-oxide, 7-hydroxy-N-desmethylchlorpromazine, N-desmethyl
      chlorpromazine sulphoxide and the total of all eight analytes were unaltered by
      quinidine. However, quinidine administration caused significant increases in the
      urinary excretions of chlorpromazine sulphoxide, N-desmethylchlorpromazine and N,
      N-didesmethylchlorpromazine sulphoxide, which indicated that compensatory
      increase in these metabolic routes of chlorpromazine might have been responsible
      for the lack of change observed in the urinary recovery of the parent drug.
      Quinidine administration produced modest decreases (1.2- to 1.3-fold) in the mean
      peak plasma concentrations and mean areas under the plasma concentration-time
      curves of 7-hydroxychlorpromazine and increases (1.3- to 1.4-fold) in these
      parameters for the parent drug chlorpromazine, but none of these changes reached
      statistical significance. Based on ANOVA the sample sizes required to detect
      these differences as significant (alpha = 0.5) with a probability of 0.8 were
      determined to vary between 15 and 42. These data suggest that CYP2D6 is involved
      in the metabolism of chlorpromazine to 7-hydroxychlorpromazine. However, genetic
      polymorphism in this metabolic process did not play a dominant role in accounting
      for the extremely large interindividual variations in plasma concentrations
      encountered with this drug.

PMID- 8739823
TI  - Lack of a kinetic interaction between fluconazole and mexiletine.
AB  - OBJECTIVE: To investigate the effect of fluconazole on the kinetics of
      mexiletine. METHODS: Six healthy male volunteers participated in a crossover
      study. On the 1st day, the subjects received 200 mg mexiletine alone. On days 2-7
      they received 200 mg fluconazole orally, and on day 8 they received 200 mg
      mexiletine and 200 mg fluconazole concomitantly. In a third phase two subjects
      received 400 mg fluconazole daily. RESULTS: No differences in concentrations were
      observed between the three phases. The area under the concentration curves (AUC)
      after administration of mexiletine alone and in combination with fluconazole 200
      mg/day were 6.63 and 7.31 micrograms.h.ml-1, respectively. CONCLUSION: These
      findings suggest that fluconazole does not inhibit mexiletine metabolism.

PMID- 8739824
TI  - Coumarin 7-hydroxylation in long-term adherents of a strict uncooked vegan diet.
AB  - OBJECTIVE: Coumarin 7-hydroxylation was investigated in 21 Finnish vegans (20
      females, one male) consuming a strict, uncooked vegan diet ("living food diet")
      and in their matched omnivorous controls, by means of an in vivo coumarin test.
      METHOD: A capsule containing 5 mg of coumarin (Venalot) was taken after an
      overnight fast, and urine samples were collected before and 2, 4 and 6 h after
      the drug administration. The extent and rate of urinary excretion of 7
      hydroxycoumarin was determined using HPLC. RESULTS: The total urinary excretion
      of 7-hydroxycoumarin during 6 h was 58 (range 23-85) and 64 (range 39-92)% of the
      administred dose in the vegan and control groups. The coumarin index (excretion
      of 7-hydroxycoumarin during the first 2 h as percentage of total excretion) was
      72% in the vegan and 78% in the control groups. A negative correlation was
      observed between the coumarin index and the consumption of wheatgrass juice by
      the vegans (r = -0.60, P < 0.01, n = 21). Proportion of slow hydroxylators
      (excreting 7-hydroxycoumarin after 4 h) was not statistically different between
      the groups (5/21 in the vegans vs 8/20 in the controls). CONCLUSION: According to
      the present study, the clearly different dietary patterns and nutrient intakes
      between the vegans and the omnivores resulted in similar extent and rate of 7
      hydroxycoumarin formation, indicating only a minor effect on coumarin hydroxylase
      (CYP2A6) activity by the plant substances in the uncooked vegan diet.

PMID- 8739825
TI  - Gender does not affect the degree of induction of tirilazad clearance by
      phenobarbital.
AB  - OBJECTIVE: Tirilazad mesylate is a membrane lipid peroxidation inhibitor being
      evaluated for the treatment of patients with subarachnoid haemorrhage (SAH);
      phenobarbital may be administered to these patients for seizure prophylaxis.
      Therefore, the effect of phenobarbital on tirilazad mesylate pharmacokinetics was
      assessed in 15 healthy volunteers (7M, 8F). METHODS: Subjects received 100 mg
      phenobarbital orally daily for 8 days in one phase of a two-way crossover study.
      In both phases, 1.5 mg.kg-1 tirilazed mesylate was administered (as a 10 minute
      IV infusion) every 6 hours for 29 doses. Three weeks separated study phases.
      Tirilazad mesylate and U-89678 (an active metabolite) in plasma were quantified
      by HPLC. RESULTS: Phenobarbital had no effect on the first dose pharmacokinetics
      of tirilazad or U-89678. After the final dose, clearance for tirilazad was
      increased 25% in males and 29% in females receiving phenobarbital + tirilazad
      versus tirilazad mesylate alone. These differences were statistically
      significant, and the degree of induction was not significantly different between
      genders. AUC(zero)-6 for U-89678 after the last tirilazad mesylate dose was
      reduced 51% in males and 69% in females. The decreases were statistically
      significant, and there was no gender by treatment interaction. CONCLUSION: The
      results show that phenobarbital induces metabolism of tirilazad and U-89678
      similarly in both men and women. Lower levels of tirilazad and U-89678 in SAH
      patients receiving phenobarbital may adversely impact clinical response.

PMID- 8739826
TI  - The pharmacokinetics of extended release felodipine in children.

PMID- 8739827
TI  - Stenosis of the pouch anal anastomosis following restorative proctocolectomy.
AB  - PURPOSE: To compare the incidence of stenosis after hand-sewn and stapled
      ileoanal anastomosis. Stenosis of the ileoanal anastomosis occurs in 5-16% of
      patients undergoing a restorative proctocolectomy but the incidence using a
      stapled technique is unknown. METHODS: Between 1976 and 1990, 266 patients
      underwent restorative proctocolectomy or proctectomy at one hospital. In two
      hundred and eighteen the anastomosis was hand sewn and stapled in 48 (single 33;
      double 15). RESULTS: Stenosis occurred in 31 (14.2%) of the hand-sewn and in 19
      (39.6%) of the stapled anastomoses. This difference was highly significant (P <
      0.001). Stenosis was not related to the size of the staple head used or to the
      stapling technique. There was no relationship between the development of stenosis
      and pelvic sepsis. Twenty six (hand-sewn 16, stapled 10) of the 48 patients with
      stenosis needed dilatation under general anaesthetic. CONCLUSION: Stapled
      anastomoses may result in a high incidence of anastomotic stenosis.

PMID- 8739828
TI  - Improved accuracy of computed tomography in local staging of rectal cancer using
      water enema.
AB  - A new technique in the preoperative staging computed tomography of rectal cancer
      using a water enema to promote full distension of the rectum was compared with
      standard CT in a non-randomised blind study. One hundred and twenty-one patients
      were enrolled. There were 57 in the water enema CT group and 64 in the standard
      group. The stage of the disease was assessed following strict criteria and tested
      against the pathological examination of the resected specimen. Water enema CT was
      significantly more accurate than standard CT with an accuracy of 84.2% vs. 62.5%
      (Kappa: 0.56 vs. 0.33: Kappa Weighted: 0.93 vs. 0.84). The diagnostic gain was
      mainly evident in the identification of rectal wall invasion within or beyond the
      muscle layer (94.7 vs. 61). The increased accuracy was 33.7% (CL95: 17-49; P <
      0.001). The results indicate that water enema CT should replace CT for staging
      rectal cancer and may offer an alternative to endorectal ultrasound.

PMID- 8739829
TI  - Anorectal sensitivity in patients with obstructed defaecation.
AB  - Patients with obstructed defaecation (OD) perform major defaecatory efforts that
      lead progressively to pudendal motor neuropathy. Anorectal sensory function in
      these patients and its possible influence in the pathogenesis of the disease have
      been little studied. In the present paper we investigated anorectal sensitivity
      to electric and thermal stimuli in patients with OD, and studied the possible
      existence of pudendal sensory neuropathy associated to their known pudendal motor
      neuropathy. Forty subjects were divided into two groups: 21 healthy controls (11
      females and 10 males; mean age 51.8 +/- 11 years, range 33-67) and 19 patients
      with OD (18 females and 1 male; mean age 48 +/- 15 years, range 20-71). The
      patients with OD suffered constipation and an obstruction sensation upon
      defaecating, even in the case of soft stools. Clinical perineometry, manometry,
      pudendal motor latency studies, external anal sphincter single fibre
      electromyography and the evaluation of sensitivity to electric and thermal
      stimuli were carried out in all cases. All pudendal motor function parameters
      showed statistically significant differences between the two groups. In the
      controls the electrical sensitivity threshold was minimal in the mid anal canal,
      where sensory receptor presence is greater. Sensitivity was significantly higher
      in the upper and lower anal canal regions (P < 0.05), and much higher in the
      rectum (P < 0.001). A similar sensory profile was recorded in the patients with
      OD, though with significantly higher thresholds at all points with respect to the
      controls. The thermal stimulus thresholds in the lower and middle anal canal were
      significantly smaller than in the upper canal region and rectum, and the
      thresholds were again higher among the patients with OD than among the controls.
      In all cases the thresholds for heat were lower than for cold stimuli. In both
      groups the motor function parameters were correlated with the sensory function
      variables, and the latter between themselves. Patients with OD presented sensory
      deterioration at all points studied in the anal canal and rectum. Sensory
      pudendal neuropathy was found to be associated with the pudental motor
      neuropathy.

PMID- 8739830
TI  - Bilateral type diverticular disease of the colon.
AB  - 7,543 double-contrast barium enema studied for the presence of diverticula which
      were classified into right-sided, left-sided and bilateral types, and the
      relationship of the frequency (detection rate) and numbers of diverticula to age
      were examined for the earlier (1982-87) and later (1988-92) periods. Diverticular
      disease was found in 22.2% of male and 15.5% of female examinees. The right-sided
      type predominated among the subjects. Frequency distribution by age of the
      bilateral type was similar to that of the left-sided type. Bilateral diverticular
      disease increased in frequency with advancing years in the sixth and seventh
      decade, the right-sided type increased in middle-aged subjects, and the left
      sided type did not. The bilateral type was composed of diverticula in the right
      colon, where numbers were greater than in the pure right-sided type, but remained
      unchanged with increasing age, and diverticula in the left colon, where numbers
      were similar to the pure left-sided type, but did not increase with age. Increase
      in the prevalence of bilateral and not pure left-sided form has contributed to
      the recent increase in diverticula in the left colon among the Japanese, and
      might have been preceded by an increase in the right-sided type.

PMID- 8739832
TI  - Ileal pouch-anal anastomosis: pregnancy, delivery and pouch function.
AB  - OBJECTIVE: To evaluate the pregnancies, deliveries and functional results of
      patients who have undergone and ileal pouch-anal anastomosis. DESIGN: A
      retrospective survey by questionnaire. SETTING: The study was conducted at a
      university hospital. SUBJECTS: Twelve women who had undergone an ileal pouch-anal
      anastomosis at the Inflammatory Bowel Disease Centre, Mount Sinai Hospital and
      who had subsequently become pregnant, were identified from the hospital records.
      A follow up questionnaire was completed by all subjects. RESULTS: Twelve patients
      had 16 deliveries. There were 10 vaginal deliveries and 6 caesarian sections.
      There were no pouch-related complication during the 16 pregnancies and there were
      two postpartum complications. CONCLUSIONS: Pregnancy is safe in women with an
      ileal pouch-anal anastomosis. Functional results are altered minimally. Vaginal
      delivery is safe and obstetric reasons should determine whether a caesarian
      section is performed.

PMID- 8739831
TI  - Characterization of the mucins produced by normal human colonocytes in primary
      culture.
AB  - Mature goblet cells filled with mucin ready for secretion represent about one
      third of the cells in primary cultures of human colonocytes. In the present study
      characterization of the mucins produced by cultured human colonocytes was made by
      histochemical methods by lectin and monoclonal antibody binding. Two monoclonal
      antibodies and three lectins (Dolichos biflorus (DBA), Helix pomatia (HPA) and
      Arachis hypogea (PNA) recognizing epitopes or sugar haptens characteristic of
      different stages of mucin glycoprotein maturation, were employed. The reactivity
      to these probes was tested both on cultured colonocytes and on tissue sections of
      the normal colon mucosa. The results show that the mucins produced in culture are
      glycosylated to the mature form, as they show the same reactivity to lectins and
      antibodies of the mucins expressed in tissue sections of the normal colon mucosa.
      In addition, it is demonstrated that cultured human colonocytes do not express
      mucins reactive to PNA, which are characteristic of tumors. Since the cultured
      colonocytes maintain the expression of differentiated functions for at least
      three days, they may offer a useful model to study metabolism, function and
      regulation of colon mucins in health and disease.

PMID- 8739833
TI  - The incidence rate of familial adenomatous polyposis. Results from the Danish
      Polyposis Register.
AB  - Based on the Danish Polyposis Register epidemiological calculations on familial
      adenomatous polyposis (FAP) were carried out. The mean annual incidence was 1.85
      x 10(-6) during the years 1971-1992, and the prevalence increasing to about 32 x
      10(-6) at the end of 1992. FAP patients constituted a decreased percentage of all
      Danish patients with colorectal cancer (0.07% in 1980-1992). The completeness of
      registration was 97% in 1983-1992. The results are similar to Finnish estimates
      based on the same direct method of calculation, and as both series are based on
      almost complete national polyposis registration in well-registered populations we
      regard our results to be close to the true incidence rate.

PMID- 8739834
TI  - Intraoperative ultrasonography in the diagnosis of hepatic metastases during
      surgery for colorectal cancer.
AB  - Approximately 20-25% of colorectal cancers have hepatic metastases at the time of
      operation and occult liver secondaries appear in 10-30% of curatively operated
      cases. Intraoperative liver ultrasonography has been reported to be the most
      accurate method for detecting colorectal metastases. A consecutive series of 119
      colorectal cancer patients was studied by routine extracorporeal preoperative
      ultrasound (EUS), inspection and palpation of the liver at laparotomy and
      intraoperative liver ultrasound (IUS). 19 patients had liver metastases at the
      time of surgery. In eight, diagnosis was by EUS. Inspection and palpation yielded
      a further seven, and IUS alone a further four. Additional lesions were detected
      in 3 patients after preoperative ultrasound and in 6 patients following
      intraoperative palpation of the liver. In a further 4 cases IUS demonstrated
      additional metastases. Follow up for a median 38 months (12-59) was by clinical
      examination and six monthly liver ultrasound. During this time 8 patients, who
      were thought to have a clear liver, developed hepatic metastases. The mean time
      from surgery to the detection of occult hepatic metastases was 14.7 (8-26) months
      and 4 of these appeared in the second year. Intraoperative ultrasonography is a
      sensitive and useful method in detecting liver metastases, and may improve
      clinical staging and the selection of patients for further therapy. However some
      occult hepatic metastases will remain undetected.

PMID- 8739835
TI  - Large bowel volvulus.
AB  - A retrospective analysis of all patients presenting with colorectal volvulus and
      managed on a colorectal service in the University Department of Surgery,
      Wellington School of Medicine, over a 15 year period was undertaken. There were
      13 males (58.6 yr.) and 11 females (55.8 yr.). The Maori to non Maori ratio was
      1:1.76. Overall 19 patients had sigmoid volvulus. Thirteen patients were admitted
      as emergencies and eight of these had a sigmoid volvulus that could not be
      deflated endoscopically, four had a caecal volvulus and one had a volvulus of the
      ascending colon. Five right hemicolectomies, three Hartmann's procedures, one
      laparotomy and tube splintage and four sigmoid colectomies were performed in
      these 14 patients. Two patients were admitted semi-acutely and deflated
      endoscopically and nine patients were admitted electively. Four patients
      developed post operative respiratory problems and four patients developed urinary
      tract infections. No patient developed an anastomotic leak. There were no post
      operative deaths. Endoscopic reduction was not found to be useful in this series.
      It is suggested that patients admitted acutely with compromised bowel should have
      a Hartmann's operation and that primary resection remains the treatment of choice
      in all other patients.

PMID- 8739836
TI  - Non-steroidal anti-inflammatory drug-induced colitis.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) may adversely affect the colon,
      either by causing a non-specific colitis or by exacerbating a preexisting colonic
      disease. Patients with NSAID-induced colitis present with bloody diarrhoea,
      weight loss, iron deficiency anaemia and sometimes abdominal pain. Colonoscopy
      may be normal or may show inflammation, ulceration or diaphragm-like stricture.
      Histology often concludes to non-specific colitis. NSAIDs may cause perforation
      or bleeding of colonic diverticula, may cause relapse to inflammatory bowel
      disease and may exacerbate bleeding of colonic angiodysplasia. Pathogenesis of
      NSAID-induced colitis is still controversial. Local and/or systemic effects of
      NSAIDs on mucosal cells might lead to an increased intestinal permeability, which
      is a prerequisite for colitis. Treatment of NSAID-induced colitis should be to
      discontinue the drug, or at least, to reduce the dose as much as possible.
      Sulphasalazine and Metronidazole have been successfully used in few studies.
      Surgery is often indicated in case of life threatening complications or
      untractable symptoms.

PMID- 8739837
TI  - Effect of repeated administration of dopamine agonists on striatal neuropeptide
      mRNA expression in rats with a unilateral nigral 6-hydroxydopamine lesion.
AB  - Striatal mRNA expression for preproenkephalin (PPE) and preprotachykinin (PPT)
      was studied in unilateral 6-OHDA lesioned rats treated subchronically with a
      range of selective and non-selective D-1 or D-2 dopamine (DA) agonists.
      Apomorphine (5 mg/kg sc), pergolide (0.5 mg/kg sc), SKF 38393 (5 mg/kg sc), SKF
      80723 (1.5 mg/kg sc), and quinpirole (5 mg/kg sc), or 0.9% saline (150
      microliters sc) were all given twice daily (except pergolide: once daily) for 7
      days. The abundance of PPE mRNA was not altered by any of these DA agonists in
      the intact striatum contralateral to the 6-OHDA lesion. Only apomorphine and
      quinpirole increased the abundance of PPT mRNA in the intact striatum. In saline
      treated 6-OHDA lesioned animals PPE mRNA was elevated (+160%, p < 0.005) and PPT
      mRNA decreased (-36%, p < 0.005) in the denervated striatum. The up-regulation of
      striatal PPE mRNA in the lesioned striatum was reversed only by pergolide. The
      downregulation of striatal PPT mRNA in the lesioned striatum was reversed only by
      apomorphine. The differential sensitivity of the striatal PPE message to the long
      acting DA agonist pergolide, and of the striatal PPT message to the mixed D-1/D-2
      DA agonist apomorphine suggests that the striatopallidal enkephalinergic pathways
      are mainly regulated by prolonged DA receptor stimulation, whereas the
      striatonigral substance P pathways are mainly regulated by mixed D-1/D-2 DA
      receptor stimulation.

PMID- 8739838
TI  - SDZ PSD 958, a novel D1 receptor antagonist with potential limbic selectivity.
AB  - SDZ PSD 958, a novel benzo[g]quinoxaline derivative exhibits the properties of a
      potent orally active selective D1 receptor antagonist. It has high affinity for
      D1-like receptors (D1, D5; pKi = 9.7-9.8) labelled by [3H]SCH23390 and is at
      least 400 fold less active at D2-like receptors (i.e. D2, D4) labelled by
      [3H]spiperone. Effects in functional tests are consistent with D1 receptor
      antagonist properties. SDZ PSD 958 inhibited apomorphine-induced rearing in mice
      and prevented prolongation of novelty-induced locomotion in rats elicited by the
      selective D1 receptor agonist CY 208-243. By contrast, SDZ PSD 958 did not induce
      catalepsy and only weakly inhibited apomorphine-induced stereotyped gnawing in
      rats. This suggests that SDZ PSD 958 preferentially inhibits responses mediated
      by dopamine systems innervating the limbic system.

PMID- 8739839
TI  - Antagonism of cocaine's stimulant effects on local cerebral glucose utilization
      by the preferential autoreceptor antagonist (+)-AJ 76.
AB  - (+)-AJ 76 is a stimulant dopamine (DA) antagonist, which has a putative
      preferential action at DA nerve terminal autoreceptors. Because it is both a mild
      stimulant and a DA antagonist, it has previously been suggested that (+)-AJ 76
      might antagonize both the euphoria and craving associated with cocaine abuse and
      withdrawal, respectively. To evaluate this hypothesis further, (+)-AJ 76 was
      evaluated for its ability to affect cocaine-induced changes in regional brain
      energy metabolism. Using Sokoloff's 2-deoxyglucose autoradiographic technique,
      (+)-AJ 76 antagonized the stimulant effect of cocaine. Although classical DA
      antagonists are known to depress regional brain energy metabolism, (+)-AJ 76 by
      itself had no effect. It is concluded that the results are consistent with the
      previously stated hypothesis that (+)-AJ 76 might be useful as a pharmacotherapy
      for treatment of cocaine abuse.

PMID- 8739841
TI  - The uptake of gamma-aminobutyric acid and glutamate by synaptosomes from the
      visual cortex of albino and pigmented rabbits.
AB  - The synaptosomal uptake of glutamate and gamma aminobutyric acid [GABA] in the
      visual cortex of albino and pigmented rabbits was compared. GABA uptake was
      similar in both pigmented and albino rabbits, but glutamate uptake was greater in
      the pigmented rabbit. The kinetics of glutamate uptake in albino and pigmented
      rabbits suggested that the number of functioning glutamate synapses may be lower
      in the albino. The significance of this with respect to the differences in visual
      processing in the two types of rabbit is discussed.

PMID- 8739840
TI  - Changes in mediobasal hypothalamic dopamine and indoleamine metabolism after
      superior cervical ganglionectomy of rats.
AB  - Eight days after bilateral superior cervical ganglionectomy (Gx) of rats,
      norepinephrine content of medial basal hypothalamus (MBH) decreased significantly
      by 44-50%. To obtain information on other possible neurochemical sequela of Gx in
      MBH, we examined the metabolism of dopamine and serotonin in MBH of Gx rats by
      employing a high pressure liquid chromatography procedure. Eight days after Gx,
      MBH dopamine levels augmented significantly. Assessment of dopamine metabolism by
      measuring dihydroxyphenylacetic acid (DOPAC)/dopamine and homovanillic acid
      (HVA)/dopamine indexes indicated a significant decrease of MBH DOPAC/dopamine
      ratio after Gx. MBH serotonin levels increased, and 5-hydroxyindoleacetic acid (5
      HIAA)/serotonin index decreased significantly in Gx rats. To examine the
      interaction Gx-induced changes on MBH dopamine and serotonin with the modified
      hormonal milieu produced by an ectopic pituitary transplant, adult male rats
      bearing an ectopic pituitary within the pectoral muscles from day 5 of life were
      submitted to Gx on day 60 of life and were studied 8 days later. MBH dopamine
      content increased significantly after pituitary grafting, an effect counteracted
      by a subsequent Gx, while Gx alone augmented MBH dopamine levels. DOPAC and HVA
      contents augmented in pituitary-grafted animals, an effect counteracted by Gx. Gx
      increased MBH serotonin content in control but not in pituitary-grafted rats.
      After pituitary grafting a decrease in MBH 5-HIAA levels was found, an effect
      reversed by Gx. Pituitary transplants brought about a significant increase of MBH
      DOPAC/dopamine index, and a significant decrease in 5-HIAA/serotonin index, both
      effects being counteracted by Gx. Gx of control rats resulted in a significant
      decrease of MBH 5-HIAA/serotonin index. Analyzed as a main effect in a factorial
      analysis of variance, Gx decreased MBH DOPAC/dopamine and HVA/dopamine indexes
      significantly. Plasma prolactin increased in pituitary-grafted rats, an effect
      further increased by a subsequent Gx. In pituitary-grafted, Gx rats plasma GH
      levels augmented significantly. The data suggest that superior cervical ganglion
      removal affects differentially dopamine and indoleamine metabolism in MBH of
      control and pituitary-grafted rats.

PMID- 8739842
TI  - Influence of aminophylline and strychnine on the protective activity of
      excitatory amino acid antagonists against maximal electroshock-induced
      convulsions in mice.
AB  - Aminophylline reversed the protective action of both, D-3-(2-carboxypiperazine-4
      yl)-1-propenyl-1-phosphonic acid (D-CPP-ene-a competitive NMDA antagonist) and
      valproate (used as a conventional antiepileptic drug for comparative purposes)
      against maximal electroshock-induced seizures. The respective ED50 values of
      aminophylline were 55.7 and 98.4 mg/kg i.p. However, aminophylline (up to 100
      mg/kg i.p.) did not influence the protective efficacy of 1-(4-aminophenyl)-4
      methyl-7,8-methyl- enedioxy-5H-2,3-benzodiazepine (GYKI 52466-a non-NMDA
      antagonist). Strychnine affected the protection provided by D-CPP-ene, GYKI
      52466, and valproate against maximal electroshock-the ED50 values of strychnine
      for the reversal of the anticonvulsive effects of D-CPP-ene, GYKI 52466 or
      valproate were 0.082, 0.35 and 0.28 mg/kg s.c., respectively. An involvement of
      strychnine sensitive glycinergic receptor-mediated events in the mechanism of the
      anticonvulsive activity of excitatory amino acid antagonists and valproate may be
      postulated. The ineffectiveness of aminophylline to reduce the anticonvulsive
      effects of GYKI 52466 may distinguish a new class of antiepileptic drugs offering
      an advantage over conventional antiepileptics in patients with epilepsy,
      requiring aminophylline for pulmonary reasons.

PMID- 8739843
TI  - Thioctic acid does not restore glutathione levels or protect against the
      potentiation of 6-hydroxydopamine toxicity induced by glutathione depletion in
      rat brain.
AB  - Decreased reduced glutathione (GSH) levels are an early marker of nigral cell
      death in Parkinson's disease. Depletion of rat brain GSH by
      intracerebroventricular administration of buthionine sulphoximine (BSO)
      potentiates the toxicity of 6-hydroxydopamine (6-OHDA) to the nigrostriatal
      pathway. We have investigated whether thioctic acid can replenish brain GSH
      levels following BSO-induced depletion and/or prevent 6-OHDA induced toxicity.
      Administration of BSO (2 x 1.6 mg i.c.v.) to rats depleted striatal GSH levels by
      upto 75%. BSO treatment potentiated 6-OHDA (75 micrograms i.c.v.) toxicity as
      judged by striatal dopamine content and the number of tyrosine hydroxylase
      immunoreactive cells in substantia nigra. Repeated treatment with thioctic acid
      (50 or 100 mg/kg i.p.) over 48h had no effect on the 6-OHDA induced loss of
      dopamine in striatum or nigral tyrosine hydroxylase positive cells in substantia
      nigra. Also thioctic acid treatment did not reverse the BSO induced depletion of
      GSH or prevent the potentiation of 6-OHDA neurotoxicity produced by BSO. Thioctic
      acid (50 mg or 100 mg/kg i.p.) alone or in combination with BSO did not alter
      striatal dopamine levels but increased dopamine turnover. Striatal 5-HT content
      was not altered by thioctic acid but 5-HIAA levels were increased. Under
      conditions of inhibition of GSH synthesis, thioctic acid does not replenish brain
      GSH levels or protect against 6-OHDA toxicity. At last in this model of
      Parkinson's disease, thioctic acid does not appear to have a neuroprotective
      effect.

PMID- 8739844
TI  - Effects on locomotor activity after local application of (+)-UH232 in discrete
      areas of the rat brain.
AB  - The preferential dopamine autoreceptor, and slightly D3 preferring, antagonist
      (+)-UH232 (cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(n-dipropylamino) tetralin)
      increases locomotor activity and synaptic dopamine release in the nucleus
      accumbens and striatum after systemic administration to the rat. As shown in this
      study, (+)-UH232, was unable to produce an increase in locomotor activity
      measured for 60 minutes after local administration into the terminal or somato
      dendritic regions of the mesolimbic dopamine pathways or into the lateral
      ventricle. Instead, a dose dependent decrease of spontaneous locomotor activity
      after local application (0.05-50.0 nmol/side) of (+)-UH232 into the nucleus
      accumbens, was seen. A similar reduction in locomotor activity was produced by
      the classical dopamine antagonist raclopride. Analysis of the dose*time
      interactions on locomotor activity did, however, indicate that there is a
      significant dose*time interaction after local application of (+)-UH232 into the
      lateral ventricle and VTA. Raclopride, on the other hand, produced only a weak
      time dependent effect in the VTA. The potential problem of Leao's spreading
      depression in micro-injection experiments were considered, however, spreading
      depression does not seem to influence the effects of (+)-UH232 locally applied
      into the nucleus accumbens. In conclusion, both (+)-UH232 and raclopride produced
      a dose dependent decrease in spontaneous locomotor activity when examined as the
      total activity count over 60 minutes after local application into the N Acc.

PMID- 8739845
TI  - Age-related decrease in responsiveness to L-DOPA is not due to changes in
      dopamine receptor mRNAs or G protein mRNAs.
AB  - To clarify the cause of the age-related decrease in the responsiveness to L-DOPA
      seen in parkinsonian patients, we studied age-related changes in the mRNA levels
      of dopamine receptors (D1, D2) and of G proteins (Gs, Gi, Go) in 22 control human
      brains aged 50-105 years. Neither the mRNA levels of dopamine receptors or of the
      G proteins changed with age. Another factor in the receptor-G protein cascade,
      such as guanine nucleotide binding, may cause the age-related decrease in
      responsiveness.

PMID- 8739846
TI  - The motor performance test series in Parkinson's disease is influenced by
      depression.
AB  - The Motor Performance Test Series (MPTS) is widely used for treatment control in
      Parkinson's disease (PD). To elucidate the possible influence of depression on
      the fine motor skills in PD, 54 patients with idiopathic PD were investigated
      with the MPTS. 27 patients with major intensity of depression were compared to 27
      age and motor disability matched patients with minor symptoms of depression,
      evaluated by the Zung depression scale. As determined by the subtest aiming, a
      significant lower ability for precise, quick complex arm-hand movements in
      depressed Parkinsonian patients was found. This result may be explained partly by
      motivation deficits in depressed patients with PD. On the other hand impairment
      of special motor loops including frontal lobe projections to specific thalamic
      subnuclei or to the caudate nucleus may cause disturbances of the subtest aiming
      in depressed Parkinsonian patients. On the basis of these findings impaired
      aiming may be explained by diminished ability for complex, semivoluntary
      movements in depressive Parkinsonian patients. The influence of psychiatric
      comorbidity on MPTS subtest aiming has to be considered in further therapy
      studies using evaluation of motor deficits by MPTS.

PMID- 8739847
TI  - Lamotrigine in the treatment of nocturnal myoclonus syndrome (NMS): two case
      reports.
AB  - In previous investigations we found an increase of D2 dopamine receptors in the
      striatum of patients with nocturnal myoclonus syndrome (NMS) after treatment with
      dopamimetics. Under the hypothesis, that, according to animal experiments, the
      glutamatergic system could be involved in this atypical dopaminergic up
      regulation in NMS. The glutamate release inhibitor lamotrigine was tested in up
      to now two NMS patients. The results and the success of this approach and its
      implications are discussed.

PMID- 8739848
TI  - The effect of chronic administration of amitriptyline on the effects of
      subsequent electroconvulsive treatment on responsiveness of alpha 1-and beta
      adrenoceptors in the rat cortical slices.
AB  - Both antidepressant drugs and repeated electroconvulsive shock (ECS) produce
      adaptive changes in cerebral neurotransmitter systems. As in the clinical
      practice ECS is used almost always after therapeutical failure of
      pharmacotherapy, we investigated presently how chronic administration of an
      antidepressant amitriptyline affects the action of subsequent multiple ECS in
      rats. Amitriptyline differed from ECS and from other classical antidepressant in
      producing no beta-downregulation and potentiating the inhibitory effect of
      protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA), on
      responses of alpha 1-adrenoceptor system to noradrenaline. The action of ECS on
      alpha 1-adrenoceptor system remained essentially unaffected by previous
      amitriptyline administration. Its downregulatory effect on responses of beta
      adrenoceptor system to noradrenaline, and particularly to isoproterenol, were
      attenuated by previous drug treatment. The present results suggest that previous
      chronic administration of antidepressant drugs may alter the effect of subsequent
      ECS.

PMID- 8739849
TI  - Pathophysiology of the plasminogen/plasmin system.
AB  - Circumstantial evidence has been provided for a role of the human fibrinolytic or
      plasminogen/plasmin system in a variety of biological phenomena. Recently,
      generation of mice with single or combined deficiencies of main components of the
      fibrinolytic system, including plasminogen, tissue-type and urokinase-type
      plasminogen activator, plasminogen activator inhibitor-1, and the cellular
      receptor for urokinase-type plasminogen activator has allowed the role of the
      fibrinolytic system in vivo to be established more conclusively. Plasminogen
      deficient mice survive embryonic development, but develop spontaneous fibrin
      deposition due to an impaired thrombolytic potential, and suffer retarded growth
      and reduced fertility and survival. Plasminogen deficiency in man is extremely
      rare, but viable, although it is associated with thrombolic complications.
      Disruption of the plasminogen activator inhibitor-1 gene in mice induces a mild
      hyperfibrinolytic state and a greater resistance to venous thrombosis, but does
      not impair hemostasis. In contrast, in man, the inhibitor deficiency results in
      delayed rebleeding. Tissue-type plasminogen activator-deficient mice have a
      reduced thrombolytic potential, whereas mice deficient in the urokinase-type
      plasminogen activator occasionally develop spontaneous fibrin deposits in tissues
      and display deficient plasmin-mediated macrophage function. Mice deficient in
      both types of activator develop normally but are significantly less fertile, have
      retarded growth and shorter survival, and display a severe thrombotic phenotype
      in normal and inflamed tissues. At present, genetic deficiencies of either type
      activator have not been reported in man. The urokinase-type plasminogen
      activator/receptor system has been implicated in localized extracellular
      proteolytic activity. Receptor-deficient mice are, however, healthy, and fertile,
      and have a normal endogenous thrombolytic capacity; their macrophages have,
      however, an impaired (urokinase-type plasminogen activator mediated) plasminogen
      activating potential. Mice with single or combined inactivation of components of
      the plasminogen/plasmin system thus may be valuable models for studying
      physiological and pathophysiological processes in vivo.

PMID- 8739850
TI  - Negative regulators of the interleukin-1 system: receptor antagonists and a decoy
      receptor.
AB  - The IL-1 system includes 2 agonists, alpha and beta, processing and transport
      molecules, receptor antagonists, signalling receptor, a decoy receptor and an
      accessory molecule. Negative pathways of regulation include the antagonists, of
      which 3 isoforms have been cloned and the type II "decoy" receptor. Molecules
      that regulate inflammation and immunity coordinatively affect different
      components of the system. The complexity of the system and the existence of
      unique pathways of negative regulation, the antagonists and the decoy receptor,
      emphasize the need for a tight control of the production and action of IL-1.

PMID- 8739851
TI  - Interaction of angiogenic basic fibroblast growth factor with endothelial cell
      heparan sulfate proteoglycans. Biological implications in neovascularization.
AB  - Basic fibroblast growth factor is an angiogenic molecule involved in several
      physiological and pathological processes, including wound repair, embryonic
      development, and tumor growth. In vitro, basic fibroblast growth factor induces
      an "angiogenic phenotype" in endothelial cells, which includes chemotaxis,
      mitogenesis, protease production, beta-integrin expression, and tube formation in
      three-dimensional gels. It acts by binding to specific tyrosine kinase receptors
      and to cell-associated heparan sulfate proteoglycans. The physiological
      significance of the interaction with cell-associated and soluble heparan sulfate
      proteoglycans is manyfold. Heparan sulfate proteoglycans protect basic fibroblast
      growth factor from inactivation in the extracellular environment and modulate its
      bioavailability. At the cell surface, soluble and cell-associated heparan sulfate
      proteoglycans may play different roles in modulating the dimerization of the
      growth factor and its interaction with tyrosine kinase receptors. Finally, they
      affect the internalization and the intracellular fate of basic fibroblast growth
      factor, suggesting that growth factor slash proteoglycan complexes are involved
      in intracellular delivery. The bioavailability and the biological activity of
      basic fibroblast growth factor on endothelial cells strictly depend on the
      glycosaminoglycan milieu of the extracellular environment. Hence the angiogenic
      activity of the growth factor in vivo might be modulated by using exogenous
      glycosaminoglycans. The capacity of glycosaminoglycans to bind to and to
      influence the biological activity of basic fibroblast growth factor depends on
      size, degree of sulfation, and disaccharide composition. In the present paper we
      discuss the physiological significance and the biochemical bases of the
      interaction of the growth factor with heparan sulfate proteoglycans and exogenous
      glycosaminoglycans with a view to the possible therapeutic use of heparin-related
      oligosaccharides as basic fibroblast growth factor agonists or antagonists in
      angiogenesis-dependent diseases.

PMID- 8739852
TI  - Regulation of hematopoietic cell proliferation and differentiation by the myb
      oncogene family of transcription factors.
AB  - The myb family of genes include the virally encoded v-myb oncogene, its normal
      cellular equivalent c-myb and two related members called A-myb and B-myb. They
      are all transcription factors that recognize the same DNA sequence (PyAACG/TG)
      and are all involved in the regulation of proliferation and differentiation in
      different cell types, including hematopoietic cells. C-myb is most highly
      expressed in hematopoietic cells and its oncogenic activation leads to
      transformation of these cells. Several lines of evidence have demonstrated that c
      myb regulates both the proliferation and differentiation of hematopoietic cells
      of different lineages. The mechanisms of action of c-myb and v-myb are becoming
      clearer, mostly through the study of the different genes that are regulated by
      these transcription factors and the cofactors with which c-myb and v-myb co
      operate. More recently the biological and biochemical functions of the B-myb and
      A-myb gene products have been investigated. Evidence for the function of the
      different members of the myb family in relation to hematopoietic proliferation
      and differentiation is presented, and the different roles of the myb genes are
      discussed.

PMID- 8739853
TI  - Serum procollagen type III peptide in chronic hepatitis B. Relationship to
      disease activity and response to interferon-alpha therapy.
AB  - The clinical significance of serum procollagen type III peptide, a marker of
      active fibrogenesis, was evaluated in 110 hepatitis B surface antigen positive
      patients with chronic hepatitis (32 chronic persistent hepatitis, 60 chronic
      active hepatitis, and 18 active cirrhosis), selected on the basis of active viral
      replication and biochemical activity, including 54 cases treated with interferon
      alpha. At presentation the procollagen type III peptide level serum was above
      normal in 48 (44%) of the 110 patients and the median value was significantly
      higher than that of healthy carriers with normal transaminases and histology (P <
      0.000005). Semiquantitative histological evaluation showed a significant
      correlation between serum procollagen type III peptide levels and
      necrosis/inflammation in the subgroup of patients with chronic active hepatitis,
      but no relationship with the score of fibrosis. Among patients treated with
      interferon-alpha and with increased fibrogenic activity (indicated by high
      pretreatment serum levels of procollagen type III peptide), peptide levels were
      significantly decreased when pretreatment levels were compared with those at 12
      months after therapy withdrawal, both in responders to interferon (P = 0.022) and
      non-responders (P = 0.012). However, serum procollagen type III peptide levels
      normalized in 75% of responders to interferon with sustained serological and
      histological remission of liver disease, but in only 21% of non-responders (P =
      0.02). These results obtained in a well-defined population suggest that serum
      procollagen type III peptide is a better marker of active fibrogenesis and
      inflammation than an indicator of the extent of fibrosis, and that interferon may
      reduce active liver fibrogenesis in chronic hepatitis B independently of its
      effect on viral replication. However, a consistent proportion (56%) of our
      chronic hepatitis B patients had normal serum procollagen type III peptide levels
      at presentation, thus precluding the clinical use of this marker both for
      diagnosis of liver injury and for monitoring the therapeutic response to
      interferon.

PMID- 8739854
TI  - Serum cholesterol levels in patients with cancer. Relationship with nutritional
      status.
AB  - Epidemiological surveys indicate an inverse relationship between cancer
      occurrence and serum cholesterol. Low serum cholesterol might be either a risk
      factor for cancer or the effect of factors associated with cancer itself, such as
      biological properties of malignant cells, tumor mass, and poor nutritional
      status. We have measured serum cholesterol in 975 selected patients admitted to
      our hospital; 496 (272 males, 224 females) had solid tumors and 479 (253 males,
      226 females) had non-neoplastic diseases. Serum cholesterol was positively
      correlated with body mass index, serum albumin, hemoglobin, and cholinesterase in
      both cancer and non-cancer subjects. Cholesterol was significantly lower in
      cancer patients than in age- and sex-matched non-cancer subjects. After
      adjustment for nutritional variables (analysis of covariance), the difference in
      cholesterol level between cancer and non-cancer subjects lost statistical
      significance in all but patients with tumors of the upper gastrointestinal tract.
      No difference was found in adjusted mean serum cholesterol between cancer
      patients subdivided according to the extension of the tumor was defined by the
      TNM system. In patients with solid tumors, serum cholesterol seems to be more
      related to the nutritional status than the presence and extension of cancer.

PMID- 8739855
TI  - Lipoprotein(a) is not elevated in non-diabetic microalbuminuric subjects. A
      longitudinal study of lipoprotein(a) concentrations and apolipoprotein(a) size
      isoforms.
AB  - Microalbuminuric non-diabetic subjects have an increased risk of cardiovascular
      disease which is not explained by standard risk factors. In diabetic patients,
      microalbuminuria is associated with increased lipoprotein(a) concentrations. We
      have determined lipoprotein(a) concentrations and duplicate measures of albumin
      excretion rate, on two occasions separated by around 3 years, in 125 Europid
      subjects aged 40-75 years without hypertension or glucose intolerance and in 49
      offspring aged 15-40 years. The apolipoprotein(a) isoform size, the major genetic
      determinant of lipoprotein(a) concentration, was also determined. There were no
      differences in lipoprotein(a) concentration between the 42 subjects who were
      microalbuminuric on either or both samples at screening (median 9.4 mg/dl, 20th
      and 80th percentiles 2.6 and 46.3 mg/dl) and the 79 who had been normoalbuminuric
      at both collections (median 10.9 mg/dl, 20th and 80th percentiles 2.9 and 53.0
      mg/dl; P = 0.58). Lipoprotein(a) concentrations were not significantly different
      between subjects with or without microalbuminuria at recell (P = 0.55) or between
      those with or without microalbuminuria classified by mean albumin excretion rate
      in either collection (P = 0.24 and P = 0.73, respectively). There were no
      significant relationships between albumin excretion rate as a continuous variable
      and lipoprotein(a) concentration, or between changes in the two variables over 3
      years. The microalbuminuric and normoalbuminuric subjects had similar
      distributions of size isoforms. There were also no differences in lipoprotein(a)
      concentration or isoform distribution between offspring of microalbuminuric and
      of normoalbuminuric subjects. In conclusion, we found no evidence that
      microalbuminuric subjects with normal blood pressure and normal glucose tolerance
      have elevated concentrations of lipoprotein(a) to explain their increased
      cardiovascular risk.

PMID- 8739856
TI  - Gamma delta + T cells in Wilson's disease.
AB  - Little is currently known about the role of gamma delta + T cells in disease
      pathogenesis. We have demonstrated elevated levels of gamma delta + T cells in
      the peripheral blood and cerebrospinal fluid of patients with Wilson's disease
      compared with other neurological diseases. The percentage of V delta 1 +/ gamma
      delta + T cells was between 20% and 50% in all patient groups; gamma delta + T
      cells in blood correlated with copper concentrations. The antigen reactivity of
      gamma delta + T cells and how the antigens relate to the gamma delta + T cells
      found in WD remains unknown. It remains unclear whether there is a direct reason
      for the elevated gamma delta + T cells population found in WD.
      Immunohistochemistry of frozen autopsy material from brain and liver of WD
      patients could allow exact localization of gamma delta + T cells and heat shock
      proteins in future studies.

PMID- 8739857
TI  - Antibody response to islet antigens in anti-CD4/prednisolone immune intervention
      of type 1 diabetes.
AB  - Cytoplasmic islet cell antibodies, glutamic acid decarboxylase autoantibodies,
      spontaneous insulin autoantibodies, and insulin-induced antibodies were analyzed
      in a 1-year follow-up study of 12 newly diagnosed patients with insulin-dependent
      diabetes mellitus aged 14 +/- 2 years (range 7-20 years) who had been initially
      treated with either multiple injections of insulin alone (control group) or, in
      addition, anti-CD4 monoclonal antibody/prednisolone (treatment group). Despite
      individual variations in islet cell antibody titers, there were no significant
      differences in the prevalence or changes in the mean titers between the two
      groups. Glutamic acid decarboxylase autoantibodies remained almost unchanged, but
      correlated with levels of islet cell antibodies. While at initiation of treatment
      only 50% of the patients from both groups had spontaneous insulin autoantibodies,
      all patients developed insulin-induced antibodies upon conventional insulin
      therapy during the course of follow-up. This was not related to islet cell
      antibody or glutamic acid decarboxylase antibody levels. The insulin requirement
      was markedly reduced through the period of follow-up, but did not significantly
      differ between the two groups. A correlation between islet cell antibody levels
      and insulin requirement was observed in the control group but not in the
      treatment group. Plasma levels of the antibodies were not associated with changes
      in stimulated C-peptide or hemoglobin A1 concentrations. Activated T-lymphocytes
      persisted in both groups of patients, but their mean levels were not
      significantly different. The reason for the absence of statistically significant
      differences between treatment and control groups could be due to the small number
      of patients in the study. In conclusion, short-term immune intervention with anti
      CD4 monoclonal antibody in addition to insulin therapy did not suppress
      autoimmune reactions towards the beta cells.

PMID- 8739858
TI  - Continuous monitoring of hydroperoxide-induced peroxidation in human erythrocytes
      by low-level chemiluminescence.
AB  - We studied the effect of cumene hydroperoxide, t-butyl hydroperoxide, and
      hydrogen peroxide on intact healthy human erythrocytes (15 g hemoglobin/dl) using
      chemiluminescence to monitor peroxidation. We measured the chemiluminescence
      spectrum, the process of hemolysis, the pH shift, and absorbance spectrum during
      the incubation with chemicals producing oxidative stress. Maximum
      chemiluminescence was reached with cumene hydroperoxide at about 50 min, but with
      t-butyl hydroperoxide at 100 min. The effect of organic hydroperoxide was
      concentration dependent, whereas the effect of hydrogen peroxide was independent
      of concentration. Peroxides induced hemolysis after 30 min. The pH shift to
      alkaline was observed in the first 20-min period. Incubation with organic
      hydroperoxides induced a decrease in absorption at 580, 545, and 345 nm. Hydrogen
      peroxide induced a decrease in the same period of time but this returned to the
      normal range by 120 min. There was no change in absorption at 420 nm with any of
      the peroxidative agents. Our results suggest that low-level chemiluminescence is
      a useful model for studying hydroperoxide-induced peroxidation in human
      erythrocytes.

PMID- 8739859
TI  - Pattern of nasal secretions during experimental influenza virus infection.
AB  - To define the pattern of secretion production during influenza virus infection,
      28 adult subjects were inoculated with influenza-A virus (H1N1) and cloistered
      for a period of 8 days. On each day, symptoms associated with virus infection
      were scored, nasal secretions were collected and nasal lavages were performed.
      Recovered lavage fluids were submitted for virus culture and assayed for
      proteins, histamine, and bradykinin. Twenty-one subjects were infected with
      influenza-A virus and had significant increases in daily secretion weights and
      symptom scores extending from day 2 to 7, post-inoculation. Plasma-derived
      proteins in the nasal lavage fluids showed an early increase to peak at day 4 and
      then decreased. Glandular proteins showed a later increase to peak at day 5.
      Bradykinin but not histamine was significantly elevated and tracked the changes
      in the glandular proteins. In contrast, a shallow increase in symptoms confined
      to day 2 post-inoculation, but no increase in daily secretion weights was
      documented in the seven uninfected subjects. There, an increase in plasma
      proteins was observed on days 1 and 2, but no change in glandular proteins was
      obvious. These results support a biphasic secretory response during influenza
      virus infection with transudation dominating the early period and glandular
      secretions contributing later.

PMID- 8739860
TI  - Long-term use of oxy- and xylometazoline nasal sprays induces rebound swelling,
      tolerance, and nasal hyperreactivity.
AB  - It has been suggested but never confirmed, that the severity of the rebound
      swelling and rhinitis medicamentosa are directly proportional to the period
      during which the drug is used, to the frequency of its use, and to the amount of
      drug administered. However, no studies have been performed to evaluate the
      effects of various amounts of the vasoconstrictors on the development of rhinitis
      medicamentosa. Moreover, no in vivo studies have yet been performed to
      investigate whether benzalkonium chloride in nasal decongestant solutions affects
      the development of rhinitis medicamentosa. This study shows that rhinitis
      medicamentosa is a condition of nasal hyperreactivity, mucosal swelling and
      tolerance induced, or aggravated, by the overuse of topical vasoconstrictors with
      or without a preservative.

PMID- 8739861
TI  - Histological changes in the nasal mucosa after hot-water irrigation. An animal
      experimental study.
AB  - Many years ago the treatment of posterior epistaxis was irrigation with hot water
      through the bleeding nose cavity, and the treatment was successful in many cases.
      The aim of this study is to explain how "hot-water irrigation" can cause
      haemostasis. Twenty-four rabbits were divided into 12 groups and their noses were
      irrigated for 5 min with hot water at temperatures ranging from 40-60 degrees C.
      After irrigation, the nose was fixed, sliced, stained, and evaluated blindly by a
      pathologist. The morphological changes-narrowing of intranasal lumen,
      vasodilation and stasis, extravasation of erythrocytes, and epithelial necrosis
      were recorded. No changes were recorded after irrigation with water of 40-44
      degrees C. Only light changes were present in the 46 degrees C group.
      Vasodilation occurred at a temperature of 48 degrees C or higher. From 48 degrees
      C, oedema of the mucosa and subsequent narrowing of the intranasal lumen was
      seen. Severe changes including epithelial necrosis, were found only in the groups
      treated with 52 degrees C or higher. The results of the study indicate that the
      haemostatic effect of hot water treatment for epistaxis may be caused by: (1)
      oedema and narrowing of the intranasal lumen, (2) vasodilation of the mucosal
      vessels, and (3) cleaning of the nose from blood coagulates.

PMID- 8739862
TI  - Hot-water irrigation as a treatment of posterior epistaxis.
AB  - The commonly-used tamponade treatment for posterior epistaxis is painful and the
      patient may need hospitalization for several days. Irrigation with water of 50
      degrees C was introduced as a treatment for posterior epistaxis more than 100
      years ago. This study compares the two treatment modalities with respect to
      effect, recurrence, pain, and length of hospital stay. Forty-four consecutive
      patients with posterior epistaxis were randomized to receive treatment with
      either hot water (21 patients) or tamponade (23 patients). In the group of
      patients treated with hot water, the treatment had to be stopped in seven
      patients (33%) because of lack of cooperation; nine patients (43%) could be
      dismissed from hospital with no need for further treatment, whereas five patients
      (24%) had recurrent epistaxis requiring additional tamponade treatment. Among the
      patients treated with tamponade, 14 patients (61%) could be dismissed from
      hospital with no need for further treatment, while nine patients (39%) had
      recurrent epistaxis requiring additional tamponade treatment. The median stay in
      hospital was five days for the group treated with hot water, and six days for the
      group treated with tamponade. Compared to the tamponade treatment, hot-water
      irrigation is almost as effective, the hospital stay is shorter, and the
      treatment is significantly less painful.

PMID- 8739863
TI  - Astemizole in combination with pseudoephedrine in the treatment of seasonal
      allergic rhinitis.
AB  - The efficacy and side effects of once-daily astemizole-D, a combination of 10 mg
      astemizole and 240 mg pseudoephedrine, were compared with those of twice-daily
      brompheniramine-D, a combination of 12 mg brompheniramine and 50 mg
      phenylpropanolamine (Lunerin), in 64 patients with seasonal allergic rhinitis
      caused by birch pollen. Efficacy was monitored by patient's diary scores,
      investigator assessments of nasal and eye symptoms and need of rescue medication
      during the 4-week study period. Both astemizole-D and brompheniramine-D reduced
      nasal and eye symptoms of allergy. There were no significant differences between
      the treatment groups regarding obstruction, but brompheniramine-D alleviated
      symptoms of rhinorrhoea and itchy eyes significantly more than astemizole-D. On
      the other hand, the patients in the brompheniramine-D group reported dry mouth,
      tiredness and drowsiness more often than those in the astemizole-D group. The
      results indicate that the two drugs are effective in the treatment of seasonal
      allergic rhinitis, but astemizole-D is better tolerated than brompheniramine-D.

PMID- 8739865
TI  - Nasal airway resistance after decongestion with a nasal spray or a bellows
      device.
AB  - Two methods for decongestion of the nasal mucosa were compared, a conventional
      nasal spray and a bellows device, the reproducibility of rhinomanometric
      measurements being investigated in both cases. Nasal airway resistance (NAR) was
      measured in 18 patients (during late autumn) before, 10 min, and 20 min after
      decongestion with an oxymetazoline solution from a bellows device, and the
      measurements were repeated one week later. About three months later (during
      spring) the measurements were repeated in the same 18 patients, but with a
      xylometazoline nasal spray being used for decongestion. With neither method were
      any differences in NAR found between 10 and 20 min after decongestion, or between
      any of the values (before or after decongestion) and the respective values
      obtained after one week. The NAR values of the undecongested total nose and the
      wider nose cavity were significantly higher during the late autumn than during
      the spring, as were also a few values after decongestion. We found no evidence
      that the bellows method is superior to the spray method in reducing NAR.

PMID- 8739864
TI  - Effect of systemically administered H1- and H2-receptor antagonists on nasal
      blood flow as measured with laser Doppler flowmetry in a provoked allergic
      reaction.
AB  - Twelve subjects with seasonal allergic rhinitis were challenged topically with
      birch pollen extract in a double-blind, double-dummy, placebo-controlled,
      randomized cross-over study. Pre-treatment was performed with either a selective
      histamine-1 (H1-) antagonist (terfenadine), a selective H2-antagonist
      (cimetidine), a combination of these drugs or a placebo. Nasal mucosa
      microcirculatory blood flow was measured with the use of laser Doppler flowmetry.
      The allergen challenge induced a decrease in the microcirculatory blood flow of
      the nasal mucosa. Pre-treatment with the H1-antagonist inhibited this effect and
      allergic symptoms, while pre-treatment with the H2-antagonist did not. No signs
      of an additive effect were seen after combination of the antagonists. Thus, H1
      receptors but not H2-receptors, seem to be of importance in the pathophysiology
      of the allergic rhinitis.

PMID- 8739866
TI  - Rhinomanometric evaluation of the improved mechanical therapeutic nasal dilator
      in patients with anterior nasal obstruction.
AB  - The effectiveness of the Improved Mechanical Therapeutic Nasal Dilator (IMTND)
      was evaluated rhinomanometrically in 33 patients (mean age: 26 years; range 18-68
      years) with anterior nasal obstruction. Using anterior rhinomanometry the
      patients were observed to have a mean total resistance of 0.376 Pa/cm3/s (range:
      0.16-0.87 Pa/cm3/s). There was a significant drop in the inspiratory nasal
      resistance by 26% after the insertion of the IMTND in the nostrils (p < 0.001).
      Following decongestion with 1% phenylephrine the resistance decreased by 41%.
      This difference was statistically significant (p < 0.001). Insertion of the IMTND
      in the decongested nostrils resulted in even higher and significant decrease in
      the nasal resistance by 59% (p < 0.001).

PMID- 8739867
TI  - Young's syndrome: a further cause of chronic rhinosinusitis.
AB  - Three males--aged 32, 35, and 27 years--presented Young's syndrome: a combination
      of obstructive azoospermia and chronic sinopulmonary infection. The evaluation of
      nasal mucociliary transport using an isotopic technique revealed mucociliary
      stasis in one case and decreased clearance in the others (< 2 mm/min). Ciliary
      ultrastructure was normal in two patients, while the other showed mucous
      hyperplasia and low ciliary density which made correct ciliary evaluation not
      possible. The clinical development of this syndrome is chronic, although less
      severe than in the other two syndromes that exhibit primary failure of
      mucociliary transport: cystic fibrosis and primary ciliary dyskinesia. Young's
      syndrome should be considered in the differential diagnosis of patients suffering
      from chronic rhinosinusitis, particularly with cystic fibrosis and primary
      ciliary dyskinesia syndrome.

PMID- 8739868
TI  - Management of post-ethmoidectomy crust formation: randomized single-blind
      clinical trial comparing pressurized seawater versus antiseptic/mucolytic saline.
AB  - This study compared the efficacy of mechanical nasal lavages with pressurized
      seawater versus nasal irrigations with saline plus benzododecinium (antiseptic)
      plus oleosorbate (mucolytic). Twenty patients agreed to participate in a
      randomized, single-blind clinical trial. All patients underwent endoscopic
      endonasal ethmoidectomy for nasal polyps. The packing was removed after 48 h and
      patients were asked to start the same day nasal lavages three times a day.
      Clinical evaluations were performed: (1) by weighing residual nasal crusts and
      secretions after 21 +/- 2 days; and (2) by using visual analogue scales to daily
      record symptom scores. Data are presented as mean +/- SEM. T-test statistics for
      two independent groups were applied. The mean residual crust and secretion
      weights were 1,756 +/- 688 mg and 1,033 +/- 422 mg in the pressurized seawater
      group, 932 +/- 414 mg and 1,222 +/- 435 mg in the antiseptic-mucolytic saline
      group. No statistical differences were found. Sample size calculations showed
      that 100 subjects in each group would be necessary to confirm a 700-mg reduction
      in residual crusts in the antiseptic/mucolytic saline group (power = 0.80; two
      sided type-I error = 0.05). Daily symptom score curves were similar in both
      groups and allowed us to give a description of post-operative complaints. The
      role of antiseptic, mucolytic and mechanical lavages in preventing post
      ethmoidectomy crust formation is discussed.

PMID- 8739869
TI  - Evaluation of Surgicel Nu-knit, Merocel and Vasolene gauze nasal packs: a
      randomized trial.
AB  - A randomised, prospective trial to evaluate Surgicel Nu-knit with Vasolene ribbon
      gauze and Merocel packs, respectively. Sixty patients (36 males and 24 females)
      undergoing bilateral nasal surgery, each having the same procedure performed on
      both sides, were recruited. The mean age was 49 years (range: 16-70 years). At
      operation, Surgicel Nu-knit was placed in one nostril, the other nostril was
      randomised to Vasolene gauze or Merocel. Twenty-four hours post-operatively,
      patients were asked to assess the discomfort experienced in either side of the
      nose while the packs were in position and on removal. The length of time and
      estimated amount of bleeding following removal of packs were also assessed.
      Surgicel Nu-knit caused significantly less discomfort both while in position and
      on removal than Vasolene gauze (p < 0.01, respectively). Compared to Merocel
      sponges, Surgicel Nu-knit caused significantly less discomfort on removal (p <
      0.01). Bleeding following removal was also significantly less compared to the
      other packs. One patient in the Surgicel group required a general anaesthetic to
      remove a retained pack fragment. At 6-week follow-up, no nasal complications were
      noted in all of the groups.

PMID- 8739870
TI  - Minimal follow-up after functional endoscopic sinus surgery. Does it affect
      outcome?
AB  - One disadvantage of functional endoscopic sinus surgery is the frequent post
      operative cavity toilet considered necessary by most surgeons, which is not only
      costly but also very unwelcome to patients. In the Royal Berkshire Hospital in
      Reading, we have reviewed a series of 120 patients who underwent FESS over an 18
      month period with minimal post-operative follow-up (first visit for cavity toilet
      at 2 weeks and, if possible, only one further visit) in order to assess outcome.
      The percentage of patients whose presenting symptom had significantly improved or
      was cured was 78%, and the mean number of follow-up visits was 2.8. We conclude
      that our policy of minimal post-operative follow-up following FESS allows results
      comparable with other series, and this policy should be further evaluated.

PMID- 8739871
TI  - Does laser turbinectomy influence local allergic inflammation in the nose?
AB  - The purpose of our study was to evaluate the effects of laser turbinectomy on
      local allergic inflammation by measuring the secretion of mediators (histamine,
      bradykinin, and TAME-esterase activity) in nasal lavage fluid after nasal
      provocation with different allergen concentrations. Our study included 15
      patients, aged 15-35 years, who displayed perennial housedust-mite rhinitis
      (positive prick test, RAST class > 2, and positive nasal provocation with
      Dermatophagoides pteronyssinus (D.p.) extract) and hypertrophic inferior
      turbinates. Rhinomanometry (Rhino-test 441, Allergopharma, Germany) and nasal
      provocation with D.p. extract (Allergopharma, Germany) followed by lavage were
      performed in all patients. The procedure was repeated three and 12 months after
      Neodynium:YAG laser turbinectomy. Three and 12 months after laser turbinectomy,
      we found a significant improvement of nasal flow (p < 0.01 and p < 0.05,
      respectively) and resistance (p < 0.1 and p < 0.01, respectively) with a tendency
      towards airway blockage in the long-term follow-up, but no changes in mediator
      levels of nasal lavages after allergen provocation, suggesting that laser
      turbinectomy has no effects on local allergic inflammation.

PMID- 8739872
TI  - Bilateral inferior turbinoplasty in chronic nasal obstruction.
AB  - Bilateral inferior turbinoplasty was performed in cases of chronic nasal
      obstruction, in which conservative treatment had failed. Forty-five patients
      without significant septal deviation and with chronic nasal obstruction were
      objectively evaluated by acoustic rhinometry (AR) before and 3-6 months after
      turbinoplasty, in order to assess the changes of the dimensions of the nasal
      cavity obtained. Mucosal turbinate hypertrophy (defined objectively by AR) was
      present in 76% of the cases. Satisfactory subjective nasal patency was achieved
      in 93% of patients. Turbinoplasty resulted in an increase of 22% at the minimum
      cross-sectional area, 37% at the cross-sectional area 3.3 cm from the nostrils,
      and 47% at the cross-sectional area 4.0 cm from the nostrils. The increase was
      not related to the subjective result of the operation. Tendency to crusting and
      to vasomotor symptoms were related to unsatisfactory results. No crusting or
      bleeding were observed.

PMID- 8739873
TI  - Turbinoplasty for concha bullosa: a non-synechiae-forming alternative to middle
      turbinectomy.
AB  - A large pneumatized middle turbinate (concha bullosa) may require surgical
      reduction. Partial middle turbinectomy, especially when done simultaneously with
      uncinectomy and ethmoidectomy, results in an increased risk for adhesion
      formation in the middle meatus. Turbinoplasty is a procedure that results in a
      significant reduction of the width of the middle turbinate without injuring its
      mucosal surfaces. A 4-year experience with this procedure showed almost complete
      elimination of the synechiae problem.

PMID- 8739874
TI  - Assessment of patient's benefit from rhinoplasty.
AB  - It is standard practice for most rhinoplasty surgeons to assess what they
      perceive to be the cosmetic outcome of their surgery. There have, however, been
      few attempts to gauge the degree of success of rhinoplasty from the patient's
      perspective. The aim of this study was to measure the benefit of rhinoplasty in
      an unselected group of patients who had undergone this procedure under the
      National Health Service (NHS). Two hundred and twenty-four patients who had
      undergone rhinoplasty or septorhinoplasty in the Department of Otolaryngology at
      Glasgow Royal Infirmary from 1990 to 1994 were surveyed by post; two
      questionnaires were administered. The Glasgow Benefit Inventory has four
      subscales which assess the patient's perception of the success of surgery, and
      the influence of surgery on the patients physical health, psychosocial function
      and social interaction. The Nasal Symptom Questionnaire (Fairley et al., 1993)-
      previously validated as an outcome measure in the context of FESS--was used to
      assess nasal symptoms. Multivariate and factor analysis was used to analyse the
      results. Four factors were extracted from the 103 responses to the Glasgow
      Benefit Inventory. The major factor of the benefit score was perception of
      surgical success which explained 50% of the variance. Three other factors
      (improvements in psychosocial functioning, social interaction and physical health
      after surgery) accounted for 10%, 5%, and 6% of the variance, respectively.
      Analysis of the Nasal Symptom Questionnaire yielded one predominant factor which
      was inversely related to perceived benefit. The outcome of rhinoplasty is
      influenced by the presence of nasal symptoms. Greater attention to nasal function
      would increase the benefit of rhinoplasty.

PMID- 8739875
TI  - Idiopathic orbital pseudotumours in adults.
AB  - We treated 24 cases of orbital pseudotumour from January 1981 through January
      1993. The clinical characteristics and treatment outcomes were analyzed
      retrospectively by reviewing the medical records, radiological studies, and
      histological examination. All patients presented with symptoms related to the eye
      (proptosis, lid swelling, limited ocular motion and/or pain, chemosis, and visual
      disturbance), while only five patients had symptoms pertaining to the ear, nose,
      and throat besides the ophthalmological symptoms. Plain X-ray findings were not
      contributory to the diagnosis. Computed tomograms (CT) showed non-specific
      findings such as hypertrophy of the extra-ocular muscles and well-defined or
      poorly defined mass. Pathological findings were non-specific, only to reveal
      benign lymphoid hyperplasia and inflammatory cell infiltration with necrotizing
      vasculitis. Twenty-four patients were treated with high-dose steroid therapy
      which resulted in a significant improvement in 10 patients (42%).

PMID- 8739877
TI  - Absolute cardiovascular risk: the basis for deciding to treat.
AB  - It has been convincingly demonstrated that a raised blood pressure is a risk
      factor for cardiovascular disease and that its reduction saves lives. It seems
      logical to suggest that the whole population's blood pressure distribution should
      be displaced downwards, since the reduction of blood pressure by only a few
      millimeters of mercury, if easily and safely achieved, would produce more disease
      prevention than could be attained by any other conceivable clinical strategy.
      Physicians already have powerful tools to lower blood pressure in individual
      patients, but must make challenging decisions as to when and how to use them.
      Blood pressure level is a reflection of relative risk and one of many risk
      factors that determine absolute risk. Reduction of blood pressure therefore does
      not cure cardiovascular disease, but reduces the risk of developing disease. The
      need for hypotensive therapy should be determined by absolute risk and the
      opportunity for successful prevention, rather than by a threshold level of blood
      pressure. The task of the physician is to assist the patient in assessing the
      balance between the potential for benefit and the burden of intervention, and to
      provide the best possible care to implement the therapeutic choice that is made.

PMID- 8739878
TI  - Ambulatory blood pressure monitoring: methodologic issues.
AB  - Blood pressure, like heart rate, is a changing physiologic variable. Like
      ambulatory electrocardiography, ambulatory blood pressure can be recorded
      intermittently throughout the day. Ambulatory blood pressure is a dynamic
      variable influenced by multiple factors, and it correlates more strongly with
      target organ damage than do static office blood pressure measurements. Office
      (but not ambulatory) measurements are subject to the placebo and physician
      pressor effect. There is a great patient variability of blood pressure
      measurements in the office compared with ambulatory methods. Ambulatory blood
      pressure devices are portable rather than 'ambulatory'. The auscultatory (listens
      for Korotkoff sounds) and oscillometric (detects maximal arterial vibrations and
      calculates diastolic blood pressure) methods are used to detect blood pressure.
      Equipment is generally safe, although mild sleep derangements have been reported.
      The 24-h blood pressure and diurnal change are usually assessed. A 24-h
      ambulatory blood pressure mean of 140/90 mm Hg or above is clearly abnormal,
      though recent data suggest that the 95th centile is 134/84 mm Hg. Correlation of
      individual blood pressure readings with diary entries may be instructive. New
      American and British validation criteria have been published to assess the
      performance of each new device that becomes available. It should not be assumed
      that newer ambulatory devices have been tested (particularly by a third party) or
      are better. Test/retest 24-h ambulatory blood pressure shows less variability
      than office measurements; however, the percentage of patients with a mean
      difference greater than +/- 5 mm Hg on repeat 24-h blood pressure measurement
      after 1 week is still surprisingly high (49.3%, systolic; 52.1%, diastolic).
      European trials are in progress to assess the prognosis of hypertension assessed
      by ambulatory compared with office blood pressure. Ambulatory blood pressure
      monitoring has been restricted for use in several clinical situations and is not
      used for the routine evaluation and management of hypertension.

PMID- 8739879
TI  - Role of whole-day ambulatory blood pressure monitoring in the management of
      hypertension.
AB  - As we learn more about hypertension, it is becoming increasingly apparent that
      conventional blood pressure measurements are fraught with potential error.
      Noninvasive ambulatory blood pressure monitoring is proving to be extremely
      valuable in both diagnosis and treatment. Advancing medical technology has
      provided small, noninvasive, reliable systems what are well tolerated by
      patients. The commercial availability of these systems facilitates their use in
      both clinical practice and in research. There have been legitimate concerns that
      continuous blood pressure monitoring may add considerably to the costs of
      diagnosing and treating hypertension. These worries, however, may be misplaced.
      If there are indeed as many patients being treated unnecessarily as has been
      suggested by many studies, then the money saved on drugs may well cover the costs
      of prolonged blood pressure monitoring. Moreover, many subjects can be spared
      unnecessary therapy. Although much work needs to be done with larger groups of
      patients followed over longer periods of time, the early experiences with 24-h
      ambulatory blood pressure monitoring have been extremely encouraging. These
      procedures have added to our understanding of hypertension and of the agents used
      in its treatment and are rapidly assuming an increasing importance in overall
      management.

PMID- 8739880
TI  - Role of hypertension in coronary artery disease.
AB  - Historically, stroke, heart failure and renal insufficiency were seen as the
      major complications of untreated hypertension. More recently, it has become
      evident that coronary heart disease is probably the most common outcome of this
      condition. Unlike the other complications of hypertension, coronary events have
      not been reduced in a meaningful fashion by traditional antihypertensive drug
      therapy. A partial explanation may lie in the fact that hypertension typically
      consists of a syndrome of inherited metabolic and cardiovascular abnormalities,
      and treatment that focuses primarily on blood pressure without taking into
      account the other factors that contribute to atherosclerotic disease can have
      only limited protective effects. The coronary hypothesis in hypertension extends
      this reasoning into 3 separate components. First is an intrinsic tendency to
      excessive proliferative and hypertrophic activity in vascular tissue, presumably
      reflecting growth-promoting activity stimulated by increased endocrine and local
      paracrine effects; second is the impact of the commonly encountered concomitant
      risk factors, including high blood pressure, that exaggerate and accelerate
      development of the underlying atherosclerotic lesions; third are hemodynamic
      factors, including increased variability and sustained elevations of blood
      pressure, that can destabilize vascular lesions and precipitate acute events.
      Treatment of these hemodynamic factors in elderly patients, whose underlying
      vascular changes are already well advanced, is likely to effectively reduce the
      incidence of vascular endpoints. In younger patients, ongoing vascular
      proliferative changes and the impact of concomitant risk factors are equally as
      important as hemodynamic forces in producing coronary disease, and effective
      treatment must take all these issues into account.

PMID- 8739881
TI  - Arterial compliance in hypertension and diabetes mellitus.
AB  - Alterations in the structure and function of large and small arterial vessels
      occur in hypertension and diabetes mellitus. These changes influence the tone and
      reactivity of the arteries, accelerate the atherogenic process and account for
      the vascular complications associated with the diseases. The widespread changes
      throughout the systemic circulation associated with hypertension and diabetes
      mellitus can alter the compliance characteristics of the arterial blood vessels.
      Changes in arterial compliance can influence blood pressure, cardiac output and
      the impedance to left ventricular ejection. The altered compliance
      characteristics of the blood vessels may represent a marker for early vascular
      damage that could ultimately predispose to major vascular events. In providing a
      more direct measure of the effects of disease on vessel wall characteristics,
      changes in arterial compliance may identify subgroups of patients at high risk of
      developing future disease-related complications. They may also act as a sensitive
      parameter to assess the effects of therapeutic interventions on arterial
      structure and tone.

PMID- 8739882
TI  - Glucose and insulin metabolism in hypertension.
AB  - Individuals with abnormal glucose and insulin metabolism have a higher incidence
      of hypertension, and recent interest has focused on the fact that patients with
      untreated essential hypertension have higher than normal plasma insulin
      concentrations, are resistant to insulin-stimulated glucose uptake and often have
      accompanying lipid disorders. The pathophysiological significance of these
      observations lies in the findings that insulin has mitogenic properties and can
      potentiate vascular smooth muscle growth, thus promoting structural changes in
      vessels and atherosclerosis. Insulin could also promote high blood pressure via
      its effect in increasing sodium reabsorption and sympathetic nervous system
      activity. A variety of therapies is available for treatment of hypertension in
      patients with metabolic complications. Lifestyle modification is considered to be
      the initial approach, with weight management the most important component.
      Although diuretics and beta-blockers have a proven record in reducing morbidity
      and mortality, they may have adverse effects on glucose, insulin and lipids and
      should be used with caution in hypertensive subjects with metabolic risks. alpha
      adrenergic blockers have favorable effects on lipids and glucose. Calcium
      antagonists have no adverse effect on glucose or insulin in patients with
      essential hypertension or diabetic patients with hypertension. ACE inhibitors, on
      the other hand, have neutral or beneficial effects on glucose, insulin and lipid
      metabolism, improving insulin sensitivity, insulin secretion, potassium balance
      and intermediary metabolism. Finally, oral hypoglycemic agents, which improve
      glucose metabolism and insulin sensitivity, can reduce blood pressure in obese,
      hypertensive subjects.

PMID- 8739883
TI  - Differing effects of antihypertensive agents on urinary albumin excretion.
AB  - Increased urinary albumin excretion is a good predictor of future progression of
      renal disease in patients with both insulin-dependent and non-insulin-dependent
      diabetes mellitus. In addition, it is an independent predictor of cardiovascular
      morbidity and mortality in patients with essential hypertension. Whether urinary
      albumin excretion represents a prognostic indicator for progressive renal
      dysfunction in patients with normal blood pressure, or essential hypertension and
      normal renal function, remains to be determined. In patients with diabetic renal
      disease, urinary albumin excretion is a good predictor for the future development
      of renal injury, and an effort has thus been made to study the success of
      antiproteinuric therapies in delaying progression of renal injury. Some
      antihypertensive agents have demonstrated abilities to reduce urinary albumin
      excretion either with or without a reduction in systemic arterial pressure.
      Whether the abilities of these drugs to protect renal function is related to
      their antihypertensive effects or antiproteinuric effects, or both, is unknown.
      This review will explore the influence of different antihypertensive agents on
      urinary albumin excretion in patients with and without essential hypertension, as
      well as in patients with nondiabetic and diabetic renal disease.

PMID- 8739884
TI  - Endothelins as cardiovascular peptides.
AB  - The normal functional state of the vasculature and the events leading to the
      development of significant arterial disease involve the interaction of important
      vasoactive substances, which play important modulating or initiating roles in the
      development of hypertension and arteriosclerosis. Three endothelins have now been
      identified, of which ET-1 is the best characterized. ET-1 is produced by
      epithelial, mesangial, neuronal and glial, and liver cells, and is the most
      potent vasoconstrictor yet found. Each endothelin is derived from a different
      gene on separate chromosomes, and each binds to at least 2 types of receptor. The
      plasma half-life of ET-1 is about 7 min, and this provides a rapid mechanism for
      adjusting vascular resistance or blood pressure. The actions of endothelin are
      mediated through several pathways of postreceptor signaling, including activation
      of the mitogen-activated protein kinase cascade, which give rise to its growth
      stimulating properties. Secretion of ET-1 from cultured endothelial cells is
      stimulated by a wide range of substances, and is inhibited by some
      prostaglandins. Endothelin in turn stimulates secretion of nitric oxide, arginine
      vasopressin and atrial natriuretic peptide, and participates in the hormonal
      control of salt and water balance. Hypoxia and ischemia augment ET-1 secretion,
      as does insulin, and this could play a role in the accelerated vascular disease
      of diabetes. ET-1 also causes bronchoconstriction and has been implicated in the
      development of acute asthma, primary pulmonary hypertension and pulmonary
      fibrosis. Its role in hypertension is still debatable, though most of the
      manifestations of congestive heart failure can theoretically be explained by the
      actions of ET-1. Endothelin also has extensive renovascular and parenchymal
      effects in the kidney. It is hoped that a fuller understanding of the role of
      endothelins in normal or pathologic vasculature will lead to effective therapy
      based on antagonism or augmentation of specific functions.

PMID- 8739885
TI  - Hemodynamic effects of renin inhibitors.
AB  - Renin inhibitors may offer an exciting new therapeutic means of blocking the
      action of the renin-angiotensin-aldosterone system. These compounds interfere
      with the first, rate-limiting step in the synthesis of angiotensin II by binding
      directly to the highly specific enzyme, renin. This approach may represent a more
      focused alternative to angiotensin-converting enzyme inhibitor therapy with an
      improved side-effect profile. Renin inhibitors given parenterally safely lower
      blood pressure in patients with essential heart failure. Under conditions of salt
      limitation, normal subjects show increases in renal plasma flow during infusion
      of renin inhibitors. The systemic and renal hemodynamic responses to renin
      inhibition are accompanied by suppression of plasma renin activity, plasma
      angiotensin II and plasma aldosterone levels. Recent scientific advances in
      discovering how to address the limitations of the low oral bioavailability of
      peptide-based compounds have made it possible to invent orally active renin
      inhibitors. Orally active renin inhibitors are presently being evaluated in
      clinical trials. The availability of intravenous and oral delivery of renin
      inhibitors broadens the potential of these agents to treat a wide variety of
      acute and chronic cardiorenal disorders.

PMID- 8739886
TI  - Glucocorticoid receptor gene expression in the embryonic rat brain.
AB  - The early ontogenetic pattern of glucocorticoid receptor (GR) gene expression was
      studied in the rat brain through embryonic days (E) 12 to 17. Using a [35S]
      labelled GR antisense RNA probe for in situ hybridization, we first detected GR
      mRNA in E13 embryos. The strongest signal was in Rathke's pouch, but the
      hypothalamic, and to a lesser degree the pontine and rhinencephalic
      neuroepithelium were also moderately labelled. Significant levels of GR mRNA were
      also detected in the choroid plexus and the epithelia lining the ventricles on
      E13. Receptor gene expression was further extended by E15 to the neuroepithelium
      and the differentiating field of several neuronal structure primordia, including
      the basal ganglia, rhinencephalon, hippocampus, pons and cerebellum. On E17, GR
      gene expression was in addition detected in the amygdala, subiculum and olfactory
      bulb and cortex. The integrity of the mRNA transcripts revealed by in situ
      hybridization was assessed by Northern blot analysis of total RNA from embryonic
      brain and pituitary. A major approximately 7-kb transcript was detected
      throughout embryonic development. An adult-like GR protein was shown by
      immunoblotting analysis to be expressed in brain and pituitary extracts already
      by E13. Based on our results, we postulate a receptor-mediated regulatory role
      for glucocorticoids in the embryonic development of the rat brain.

PMID- 8739887
TI  - Acute intracerebroventricular administration of neuropeptide Y stimulates
      corticosterone output and feeding but not insulin output in normal rats.
AB  - The effect of acute intracerebroventricular (i.c.v.) injection of neuropeptide Y
      (NPY) on basal and glucose- or arginine-stimulated insulinemia was studied in
      anesthetized and conscious rats. Basal insulinemia was not significantly
      increased relative to control values after NPY injection. The insulinemic
      response to an intravenous bolus of glucose or arginine was unaffected by prior
      NPY injection, glycemic profiles being identical in control and NPY-injected
      rats. Plasma NPY concentrations were double the corresponding control values at
      20 min after i.c.v. NPY injection, but this difference was not statistically
      significant. Although peripheral NPY inhibits insulin secretion, these elevated
      plasma NPY concentrations occurred too late to explain the lack of effect of
      i.c.v. NPY on substrate-induced insulin secretion. Compared to control rats,
      marked increases in corticosteronemia were observed after i.c.v. NPY injection in
      conscious animals. When allowed to eat ad libitum at the end of each experiment,
      NPY-injected rats consumed significantly more chow in 20 min than controls. We
      conclude that although acute i.c.v. injection of a maximum dose of NPY had
      definite effects on plasma corticosterone concentrations and feeding, it favored
      neither the basal nor the substrate-induced insulin output.

PMID- 8739888
TI  - Hypothalamic-pituitary-adrenal response to chronic stress in five inbred rat
      strains: differential responses are mainly located at the adrenocortical level.
AB  - The effects of chronic stress on the hypothalamic-pituaitary-adrenocortical (HPA)
      axis were studied in five inbred rat strains, i.e. Brown Norway (BN), Fischer
      (FIS), Lewis (LEW), Spontaneously Hypertensive (SHR) and Wistar Kyoto (WKY).
      Previously, these rat strains had been shown to display clear behavioral
      differences in the forced swimming test that presumably measures depression-like
      behavior, BN and WKY being more passive than the other strains. Here we test the
      hypothesis that the differences in behavioral immobility might be associated with
      an abnormal HPA response to chronic immobilization (IMO) stress. In stressnaive
      rats under basal conditions (morning) there were no differences among strains in
      adrenal weight, serum adrenocorticotropin hormone (ACTH) and corticosterone (B)
      levels, cortictropin-releasing factor (CRF) mRNA in the hypothalamic
      paraventricular nucleus (PVN) and hippocampal glucocorticoid and
      mineralocorticoid receptor (GR and MR) mRNA. After chronic IMO, basal serum ACTH
      levels were increased in LEW, SHR and WKY, but not in BN or FIS rats, whereas
      basal B levels were increased in BN, FIS, SHR and WKY rats, but not in LEW. The
      increase in adrenal weight was also strain dependent and correlated negatively
      with chronic IMO-induced hypercorticosteronemia. These peripheral differences
      among strains were not observed at central levels. Thus, chronic IMO increased
      the CRF mRNA content in the PVN, analyzed by in situ hybridization, similarly in
      all strains. In addition, after chronic IMO no differences were found among
      strains in hippocampal GR mRNA and RM mRNA contents. Considering data from all
      strains together, chronic IMO reduced the GR mRNA (50-60%) content in the
      hippocampal CA1, CA3 and DG areas, and slightly diminished (11-13%) MR mRNA
      levels in CA1 and CA3 areas. The present results indicate that: (i) chronic IMO
      down-regulates GR mRNA in the hippocampus and slightly up-regulates CRF mRNA in
      the hypothalamic PVN similarly in all strains; (ii) after chronic IMO interstrain
      differences were observed in serum ACTH and B levels as well as adrenal
      hypertrophy; (iii) some changes are probably located at the adrenal level since
      changes in serum B level and adrenal weight were not related to changes in ACTH;
      (iv) in LEW and WKY rats, B hyporesponsiveness to chronic IMO might be linked to
      low adrenal sensitivity to ACTH, and (v) HPA axis changes induced by the chronic
      IMO procedure are not related to previously reported data on depressive-like
      behavior of BN and WKY in the forced swimming test.

PMID- 8739889
TI  - Unidirectional specific and modulated brain to blood transport of corticotropin
      releasing hormone.
AB  - Corticotropin-releasing hormone (CRH) is produced and acts both within the
      central nervous system and at several peripheral sites. However, it is not known
      whether CRH is able to cross the blood-brain barrier (BBB) in either direction,
      or whether the central and peripheral compartments are independent. We studied
      the transport across the BBB of both human/rat CRH (hCRH) and ovine CRH (oCRH)
      using the native peptides labeled with 125I at the histidine residue, thereby
      avoiding the use of other synthetic modifications. No apparent transport of
      either hCRH or oCRH into the brain from blood was found, as measured by multiple
      time regression analysis after intravenous injection of the labeled peptides.
      There were no significant differences between the two forms of the CRH peptide.
      However, both hCRH and oCRH were rapidly transported out of the brain after
      intracerebroventricular injection, with half-time (t1/2) disappearances of 11.1
      (hCRH) and 15.1 min (oCRH); the transport rate was significantly different for
      the human and ovine forms. The transport of hCRH could be specifically inhibited
      by 5 nmol of unlabeled hCRH (t1/2 = 17.7 min) but not by the same dose of the
      synthetic analog alpha CRH12-41. The process could also be inhibited by
      pretreatment with aluminum chloride (t1/2 = 18.8 min). An indirect influence of
      the endogenous opiate modulating peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2, 5 nmol)
      was apparent by a change in the initial distribution within the brain. In
      conclusion, there is a specific unidirectional brain to blood transport system
      for CRH. This transport system in the mouse has a greater affinity for the
      human/rat than for the ovine form of the peptide, is inhibited by hCRH itself,
      and can be disrupted by pretreatment with aluminum. By facilitating the rapid
      clearance of central CRH, this transport system could be involved in the
      regulation of central CRH levels and could allow central CRH to reach the general
      circulation and act at peripheral sites.

PMID- 8739890
TI  - The ontogeny of pit-1 expression in the human fetal pituitary gland.
AB  - Pit-1 expression has been reported to be cell-type-specific in the adult human
      pituitary and in human pituitary adenomas. In contrast, studies of rodent fetal
      adenohypophysial development as well as mature rodent glands have indicated that
      the pit-1 mRNA is ubiquitously expressed and the protein is under translational
      control. To determine the ontogeny and localization of Pit-1 expression in the
      human fetus, we examined fetal pituitaries (n = 23) at various stages of
      gestation from 6 weeks to term using in situ hybridization (ISH) for pit-1 mRNA,
      immunohistochemical localization of Pit-1 protein, and combined ISH for pit-1
      mRNA with immunohistochemistry for pituitary hormones. At 6 and 7 weeks of
      gestation, the cells surrounding both limbs of Rathke's cleft showed a moderate
      specific signal for pit-1 mRNA. At 7 weeks, only a few cells were immunoreactive
      for ACTH and there was no definite colocalization of that hormone with pit-1
      mRNA. At 8 and 9 weeks of gestation, there was definite preferential expression
      of pit-1 mRNA in cells containing growth hormone (GH) but not ACTH, as well as in
      cells with no detectable hormone immunopositivity. At midgestation and after,
      there was clear correlation between pit-1 mRNA expression and hormone content;
      cells with GH, prolactin and/or thyrotropin immunoreactivity had abundant pit-1
      mRNA, whereas those containing ACTH, FSH or LH were negative for pit-1 mRNA by
      ISH and its protein by immunohistochemistry. The signal for pit-1 mRNA was
      stronger in intensity and present in more cells in fetal than in adult
      adenohypophyses. The ontogeny of pit-1 mRNA expression indicates that it precedes
      the onset of pituitary hormone detection. Its abundance in the human pituitary
      early in gestation may reflect its role in cytodifferentiation and cell
      proliferation. The correlation between pit-1 mRNA detection and Pit-1 protein
      localization is consistent with a cell-type-specific pretranslational regulatory
      mechanism for Pit-1 expression in the developing human adenohypophysis.

PMID- 8739891
TI  - Expression of Fos-related antigens, oxytocin, dynorphin and galanin in the
      paraventricular and supraoptic nuclei of lactating rats.
AB  - The magnocellular oxytocin neurons within the paraventricular and supraoptic
      nuclei (PVN and SON) of the hypothalamus are important relays in the milk
      ejection reflex in lactating animals, and are activated by suckling. It has been
      suggested that proto-oncogene transcription factors such as Fos/Jun act as early
      nuclear transducers of sensory stimuli in neurons. Therefore, we have studied
      with immunohistochemistry Fos-related antigens (FRAs) as a marker for neuronal
      activity in the PVN and SON during suckling in lactating rats. In nonlactating
      rats, only few cells exhibiting FRAs were observed in these nuclei. Also in
      lactating rats subjected to continuous suckling Fos-like activity was low. In
      contrast, lactating rats separated from their pups for 4 h and then exposed to
      suckling for 1 h expressed strong Fos-like immunoreactivity, both in vasopressin
      and oxytocin neurons. Using in situ hybridization and immunohistochemistry we
      have also investigated the expression of the mRNAs for oxytocin, dynorphin,
      galanin and galanin message-associated peptide and of oxytocin and dynorphin in
      the PVN of lactating and nonlactating rats. In lactating rats, an increase in
      oxytocin and dynorphin and their mRNAs was observed, whereas mRNAs for galanin
      and galanin message-associated peptide were downregulated. With the help of
      immunohistochemistry and double-staining methods, a substantial coexistence
      between oxytocin- and dynorphin-like immunoreactivities was shown in
      magnocellular neurons. These results indicate that FRAs are activated in the PVN
      in the beginning of a suckling period, while this response cannot be seen after
      continuous stimulation. Furthermore, in the PVN of lactating rats, an
      upregulation of oxytocin and dynorphin occurs while galanin expression decreases.
      Finally, the coexistence between oxytocin and dynorphin is more pronounced in
      lactating rats and nonlactating female rats than has previously been described in
      male rats.

PMID- 8739892
TI  - Effects of central GABAB receptor modulation upon the milk ejection reflex in the
      rat.
AB  - In order to investigate the role of central GABAB receptors in the control of the
      milk ejection reflex, we have examined the effects of third ventricular and
      bilateral supraoptic nucleus (SON) injections of a GABAB receptor agonist
      (baclofen) and antagonist (hydroxy-saclofen) on the milk ejection reflex in the
      urethane-anaesthetised rat. In addition, microdialysis studies have evaluated
      whether the activation of GABAB receptors in the SON is able to modulate the
      release of GABA and glutamate, two major neurotransmitters involved in the
      regulation of the milk ejection reflex. Intracerebroventricular injections of
      baclofen (n = 9) in doses of 10, 50 and 100 pmol inhibited the milk ejection
      reflex in a dose-dependent manner, without affecting the electroencephalogram or
      attenuating the intramammary pressure response to intravenous injection of 0.5 mU
      exogenous oxytocin. Hydroxy-saclofen given into the third ventricle in doses of
      100 pmol (n = 2) and 500 pmol (n = 4) did not modify the pattern of the milk
      ejection reflex. Bilateral SON microinfusions of baclofen in doses of 80 (n = 2)
      and 200 pmol (n = 4) did not modify the pattern of the milk ejection reflex. In
      microdialysis experiments (n = 8), inclusion of baclofen into the microdialysate
      at a concentration of 500 microM had no effect upon basal or potassium-stimulated
      GABA and glutamate outflow. These results show that the activation of GABAB
      receptors located outside, but not within, the SON are capable of inhibiting the
      milk ejection reflex. In contrast to our previous findings regarding the GABAA
      receptor, we found no evidence for a tonic role of GABAB receptors within the
      neural network inducing the periodic synchronous bursting of oxytocin neurons
      during suckling.

PMID- 8739893
TI  - Evidence of a peripheral and a central effect of oxytocin on pancreatic hormone
      release in rats.
AB  - The aim of the present study was to investigate how oxytocin given subcutaneously
      (SC) and intracerebroventricularly (ICV) influences the secretion of insulin,
      glucagon and glucose and to investigate whether the effect on these variables of
      suckling in lactating rats is mediated by oxytocinergic mechanisms. Male rats
      were given oxytocin in doses of 2 or 20 ng (SC) or 2 or 200 ng (ICV). Trunk blood
      was collected and hormone analysis performed by radioimmunoassay. Subcutaneous
      injections of oxytocin increased insulin, glucagon and glucose levels
      significantly. Two nanograms oxytocin given ICV had no effect on glucagon and
      glucose levels but caused a significant rise in insulin levels at this time
      point. This effect was abolished by atropine. The oxytocin antagonist 1-deamino-2
      D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin administered ICV increased insulin levels itself
      and therefore the effect on oxytocin-induced insulin secretion was difficult to
      evaluate. Intracerebroventricular injections of 200 ng oxytocin caused a
      significant rise not only of insulin but also of glucagon and glucose levels.
      Since this dose of oxytocin also caused a substantial rise of circulating
      oxytocin levels, these effects on glucose and glucagon may have been exerted at a
      peripheral site. Suckling in lactating rats was followed by a significant
      increase of glucose and glucagon levels. These effects were completely abolished
      by pretreatment with an oxytocin antagonist. In conclusion, oxytocin seems to
      influence pancreatic hormone secretion by two different mechanisms. Elevated
      circulating levels of oxytocin-e.g. as seen in response to suckling in lactating
      rats-are accompanied by a rise of glucagon and glucose levels which is blocked by
      the oxytocin antagonist. In contrast, nanogram amounts of oxytocin administered
      ICV cause a rise of insulin levels. Since this effect was blocked by atropine, it
      is likely to involve activation of vagal cholinergic neurons, innervating
      pancreatic beta-cells.

PMID- 8739894
TI  - Presence of nitric oxide synthase in the sheep pineal gland: an experimental
      immunohistochemical study.
AB  - By use of immunohistochemistry, a dense network of nerve fibres immunoreactive to
      the neuronal form of nitric oxide synthase (NOS, subtype I) was demonstrated in
      the pineal gland of sheep. The NOS-immunoreactive fibres were located in the
      pineal capsule and the connective tissue septae of the gland, but fibres were
      also present intraparenchymally between the pinealocytes. NOS-immunoreactive
      nerve fibres were still present in the gland 1 month after bilateral removal of
      the superior cervical ganglia. By use of an antibody directed against endothelial
      NOS (subtype III), only pineal blood vessels were stained. This staining was
      still present in the ganglionectomized animals. No difference was found in the
      staining between the control animals and the ganglionectomized ones. The
      pinealocytes were not stained, neither by the antibody against neuronal NOS nor
      by the antibody against endothelial NOS. By use of double immunohistochemical
      stainings, NOS was in many nerve fibres colocalized with vasoactive intestinal
      peptide. Western blot analysis of supernatant fractions of sheep pineal
      homogenates showed the presence of a band corresponding to the neuronal NOS.
      Thus, the present data show a prominent innervation of the sheep pineal gland
      with NOS-immunoreactive nerve fibres with their origin outside the sympathetic
      nervous system, indicating an influence of NO on the pinealocyte metabolism from
      non-sympathetic nerve fibres in this species. The presence of NOS in both
      perivascular nerve fibres and the endothelium of the blood vessels of the gland
      suggests a role of NO in the regulation of the circulation of the sheep pineal
      gland.

PMID- 8739895
TI  - Relationship of plasma growth hormone to slow-wave sleep in African sleeping
      sickness.
AB  - Human African trypanosomiasis (sleeping sickness) is a unique disease model of
      disrupted circadian rhythms in the sleep-wake cycle and cortisol and prolactin
      secretion. This study examined the temporal relationship between growth hormone
      (GH) secretion and the sleep-wake cycle in 8 infected African patients and 6
      healthy indigenous African subjects. Twenty-four-hour sleep patterns were
      recorded by polysomnography and hourly blood samples analyzed for plasma GH. No
      relationships between the mean normalized plasma GH levels (Z scores) and the
      sleep stages (wakefulness, sleep stages 1 and 2 ('light' sleep), slow-wave sleep
      (stages 3 and 4, SWS), and rapid eye movement (REM) sleep) were found in the
      patients or healthy subjects. However, when the time of sampling of the plasma GH
      concentrations was lagged by 16 min with respect to the occurrence of the various
      sleep stages, significant correlations were found between plasma GH
      concentrations and SWS in both healthy subjects and patients. Thus, the
      association between SWS and GH secretion persisted even in the presence of
      disrupted circadian rhythms, further supporting the concept that sleep and the
      stimulation of GH secretion are outputs of a common mechanism.

PMID- 8739896
TI  - Genetic variability in adult bone density among inbred strains of mice.
AB  - More than 70% of the variability in human bone density has been attributed to
      genetic factors as a result of studies with twins, osteoporotic families, and
      individuals with rare heritable bone disorders. We have applied the Stratec XCT
      960M pQCT, specifically modified for small skeletal specimens, to analyses of
      bones from 11 inbred strains (AKR/J, BALB/cByJ, C3H/HeJ, C57BL/6J, C57L/J,
      DBA/2J, NZB/B1NJ, SM/J, SJL/BmJ, SWR/BmJ, and 129/J) of female mice to determine
      the extent of heritable differences in peak bone density, pQCT scans were taken
      of femurs from (a) 12-month-old inbred strain females and (b) a subset of four
      strains (C3H/HeJ, DBA/2J, BALB/cByJ, C57BL/6J) at 2, 4, and 8 months. In
      addition, pQCT scans were also obtained from L5-L6 vertebrae and proximal
      phalanges from the same subset of four inbred strains at 12 months of age.
      Comparison of bone parameters among inbred strains revealed significant
      differences at each of the three sites investigated. Femoral and phalangeal bones
      differed among strains with respect to total and cortical density, mineral, and
      volume. Only cortical bone parameters were significantly different among strains
      at the vertebral site. With respect to strain differences, the highest value for
      any given bone parameter was found in the C3H/HeJ strain, whereas C57BL/6J values
      were absolutely, or statistically, the lowest. Similarly, with respect to bone
      sites, cortical bone density was significantly correlated among strains. On the
      other hand, we found that none of the femur, vertebral, or phalangeal parameters
      correlated with body weight, even though body weight varied by 86% among those
      inbred strains. The developmental studies of femurs conducted at 2, 4, and 8
      months of age with C3H/HeJ, DBA/2J, BALB/cByJ, and C57BL/6J females showed
      differences in total density among strains at 2 months and thereafter. Adult peak
      bone density was typically achieved by 4 months, whereas femurs continued to
      lengthen for 4 to 8 months thereafter. We conclude that (1) major genetic effects
      on femoral, vertebral, and phalangeal bone density are detectable among inbred
      strains of mice; (2) cortical bone density shares common genetic regulation at
      the three measured sites; and (3) within the femur, genes that regulate length
      and density are different.

PMID- 8739897
TI  - In vivo measurement of human tibial strains during vigorous activity.
AB  - Our understanding of mechanical controls on bone remodeling comes from studies of
      animals with surgically implanted strain gages, but in vivo strain measurements
      have been made in a single human only once. That study showed that strains in the
      human tibia during walking and running are well below the fracture threshold.
      However, strains have never been monitored in vivo during vigorous activity in
      people, even though prolonged strenuous activity may be responsible for the
      occurrence of stress fractures. We hypothesized that strains > 3000 microstrain
      could be produced on the human tibial midshaft during vigorous activity. Strains
      were measured on the tibiae of two subjects via implanted strain gauges under
      conditions similar to those experienced by Israeli infantry recruits. Principal
      compressive and shear strains were greatest for uphill and downhill zigzag
      running, reaching nearly 2000 microstrain in some cases, about three times higher
      than recorded during walking. Strain rates were highest during sprinting and
      downhill running, reaching 0.050/sec. These results show that strain is
      maintained below 2000 microstrain even under conditions of strenuous activity.
      Strain rates are higher than previously recorded in human studies, but well
      within the range reported for running animals.

PMID- 8739898
TI  - Neural involvement in post-traumatic osteopenia: an experimental study in the
      rat.
AB  - The effect of sciatic nerve resection on post-traumatic bone loss and mechanical
      strength of the ipsilateral (IL) and contralateral (CL) femoral shafts and necks
      was studied 25 days after a tibial fracture. We subjected 45 male rats to a
      standardized tibial fracture, stabilized it with a modular intramedullary nail
      and then randomly allocated the animals to two groups: right sciatic nerve
      resection (SNR group) or sham operation (sham group). All of the operated
      hindlimbs were further immobilized in a plaster cast to avoid unequal loadbearing
      between the two groups. After 25 days of healing, 85Sr incorporation in the IL
      femora was 10% lower in the SNR group compared to the sham group, indicating a
      lower bone mineralization after sciatic nerve resection. The bone mineral content
      was 15% higher in the SNR group ipsilaterally. Accordingly, the bending moment
      and energy absorption in the femoral midshaft were higher in the SNR group
      compared to the sham group. The sciatic nerve resection protected the femoral
      shaft against the normally occurring post-traumatic bone loss after a tibial
      fracture. This protective effect of the neurectomy also occurred in the femoral
      neck, but not to the same extent. A protective effect was also present in the CL
      femur, suggesting additional systemic effects of the sciatic nerve resection.

PMID- 8739899
TI  - Microstructure-microhardness relations in parallel-fibered and lamellar bone.
AB  - Understanding the mechanical function of bone material in relation to its
      structure is a fascinating but very complicated problem to resolve. Part of the
      complexity arises from the hierarchical structural organization of bone.
      Microhardness measurements, initially on relatively simply structured parallel
      fibered bone, show a marked anisotropy in three orthogonal directions. This may,
      in part, be due to the highly anisotropic structure of the basic building block
      of bone, the mineralized collagen fibril. Microhardness measurements made face-on
      to the layers of crystals and collagen triple helical molecules, show much lower
      values than those made edge-on to these layers. Microhardness measurements of the
      much more complex "rotated-plywood" structure of lamellar bone, reveal the well
      known general tendency toward anisotropy in relation to the long axis of the
      bone. A detailed examination of microhardness-microstructure relations of
      lamellar bone, however, shows that only in certain orientations can microhardness
      values be related directly to a specific attribute of the lamellar structure.
      Clearly, the gradual tilting and rotating of the mineralized collagen fibrils
      that form this structure produce a material that tends toward having isotropic
      microhardness properties, even though its basic building block is highly
      anisotropic. This may be an important structural attribute that allows lamellar
      bone to withstand a variety of mechanical challenges.

PMID- 8739900
TI  - Influence of vitamin D status on hyaluronan localization in bone.
AB  - The distribution of hyaluronan was investigated in the proximal tibiotarsal bones
      of normal (vitamin D-treated) chicks, and chicks with rachitic lesions induced by
      vitamin D deficiency. Localization studies using a biotinylated hyaluronan
      binding probe revealed that in vitamin D-treated chicks, a high level of
      hyaluronan staining was present in upper proliferative zone cartilage and upper
      hypertrophic zone cartilage. Hyaluronan staining was greatly reduced in the zone
      of provisional calcification. In the metaphyses and diaphyses of normal chicks
      hyaluronan was predominantly localized to the non-bone-forming surfaces of
      osteoblasts but was also present on the basolateral surfaces of lining cells and
      osteoclasts. Marked changes in hyaluronan distribution were observed in vitamin D
      deficient chicks. The amount of hyaluronan present in proliferative zone growth
      cartilage was similar to control chicks, although with a more widespread
      distribution, extending into lower proliferative zone cartilage. In the zone of
      hypertrophy/calcification, biochemical analyses revealed that hyaluronan levels
      in rachitic chicks were about 3.6 times greater than in vitamin D-treated chicks;
      localization studies demonstrated that this increase was associated with the
      presence of hyaluronan-positive spindle-shaped cells in the metaphyseal vascular
      spaces. Intense hyaluronan staining was also associated with abundant spindle
      shaped cells occupying the marrow spaces of rachitic diaphyseal bone. The
      distribution of hyaluronan in vitamin D-treated chick bone, and the alterations
      observed in rachitic tissue suggests a role for hyaluronan in endochondral bone
      formation.

PMID- 8739901
TI  - Determinants of vertebral fracture prevalence among native Japanese women and
      women of Japanese descent living in Hawaii.
AB  - Age-adjusted prevalence of vertebral fracture has been reported to be higher
      among native Japanese women than among women of Japanese descent living in
      Hawaii. In this cross-sectional population-based study, we examined a variety of
      potential risk factors for associations with prevalent vertebral fractures and
      investigated whether these factors could explain the difference in vertebral
      fracture prevalence between native Japanese and Japanese-American women. Spine
      radiographs and data on spine bone mineral density (BMD) and other potential risk
      factors were collected among 802 Japanese women aged 50-88 years living in
      Hiroshima and 840 Japanese-American women aged 52-88 years living in Hawaii. In
      logistic regression analysis, BMD was a major predictor of prevalent vertebral
      fracture. In linear regression models, weight, age, and menstrual history (age at
      menopause or years between menarche and menopause) were significantly associated
      with BMD and thus might contribute to fracture risk indirectly through their
      effects on BMD. However, age and menstrual history provided additional and
      complementary information about fracture prevalence after adjusting for BMD.
      These variables together explained much of the difference in vertebral fracture
      prevalence between the two study populations. We conclude that the observed
      difference in age-adjusted prevalence of spine fracture between native Japanese
      and Japanese-American women was accounted for primarily by the differences in
      BMD, duration of estrogen exposure, and/or duration of estrogen deficiency. Thus,
      current BMD is a major but not the sole risk factor for vertebral fractures. Age
      related and menopause-related mechanisms may also play an important role in spine
      fracture independent of BMD.

PMID- 8739902
TI  - Ovariectomy-induced high turnover in cortical bone is dependent on pituitary
      hormone in rats.
AB  - The aim of this study is to examine the interrelationship of pituitary and
      ovarian hormone deficiency on the regulation of bone growth and bone formation
      rate. 48 female rats, at 3 months of age, were divided into age-matched intact
      control, hypophysectomized (HX), ovariectomized (OV), and HX + OV groups. Ten
      rats were killed at 3 months of age as baseline controls, and the rest of the
      animals were killed 5 weeks after surgery. Serum levels of osteocalcin and
      dynamic histomorphometry on the periosteal surface of the tibial shaft and fifth
      lumbar vertebrae were measured to evaluate systemic and local bone turnover.
      Tibial and fourth lumbar vertebral bone area, bone mineral content, and bone
      density were measured by dual-energy X-ray absorptiometry (DXA). Our results
      confirmed that OV increased and HX suppressed systemic and periosteal bone
      formation parameters in both bone sites, OV increased and HX suppressed the gain
      in bone size and bone mass. When OV rats were HX, the serum levels of osteocalcin
      and periosteal bone formation parameters of the tibial shaft and the fifth lumbar
      vertebrae were, however, depressed and did not differ from that of the HX alone.
      DXA results show that the effect of OV on bone size and bone mass is also
      abolished by HX. In conclusion, we have demonstrated that OV increases tibial and
      lumbar vertebral bone formation and bone growth and this effect is pituitary
      hormone dependent.

PMID- 8739903
TI  - Regulation of human osteoblast integrin expression by orthopedic implant
      materials.
AB  - Integrins are transmembrane proteins that mediate attachment to extracellular
      matrix (ECM) proteins. Integrins act as ECM receptors and are believed to play a
      role in signal transduction and gene regulation, potentially influencing several
      cellular functions, including differentiation, growth, and migration. Several
      integrins have previously been found in bone cells in vivo and in vitro. Because
      the biologic fixation of orthopedic implants depends on optimal cell interactions
      at the interface, we examined whether integrins are involved in the attachment of
      osteoblasts to implant materials. In this study, we have used
      immunohistochemistry to examine the expression of integrins in primary human
      osteoblasts cultured on tissue culture polystyrene (PS), and rough and polished
      disks of the orthopedic alloys titanium-aluminum-vanadium (Ti) and cobalt-chrome
      molybdenum (CC). The integrin subunits, alpha 2, alpha 3, alpha 4, alpha 5, alpha
      v, alpha 6, beta 1 and beta 3, were expressed by primary human osteoblasts
      cultured on PS coated with various ECM molecules. However, alpha 5 and alpha 6
      were notably absent in cells attached to the alloys. Also, alpha 3 was not
      present on rough Ti, polished CC, or rough CC, and beta 3 was not expressed by
      cells on rough CC. Thus, the nature of the metal alloy appeared to influence the
      expression of particular integrins. As a result, the ability of cells to adhere
      to and receive messages from the extracellular matrix may also be influenced by
      the substratum. These differences may explain previously observed differences in
      degree of cell attachment to these metals.

PMID- 8739904
TI  - Determination of connectivity density in human iliac crest bone biopsies assessed
      by a computerized method.
AB  - The aim of the present study was to design a computer program (based on the
      ConnEulor principle) for direct measurement of 3-D connectivity density in iliac
      crest bone sections, as used for conventional histomorphometry. We used the
      physical disector principle and developed an algorithm for nonlinear alignment of
      the disector pairs. 3-D connectivity was evaluated in transiliac specimens from
      30 nonselected autopsy cases of 14 men (age range 20-84 years) and 16 women (age
      range 20-96 years). In order to visualize the findings from the disector pairs, 3
      D reconstruction was performed for two of the iliac crest biopsies. The designed
      computer program aligns the two sections forming a disector pair and
      automatically depicts the differences between the images, thereby making correct,
      direct connectivity density measurements available for conventional bone
      research.

PMID- 8739905
TI  - Cortical and total bone mineral content of the radius: accuracy of peripheral
      computed tomography.
AB  - The aim of the study was to evaluate the accuracy of an XCT 960 Stratec
      peripheral quantitative computed tomography (pQCT) device in assessing bone
      mineral content of the radius. We scanned 27 left forearm specimens excised from
      cadavers and focused on cortical bone mineral content (BMCc) at the junction of
      the middle and distal third and on total bone mineral content (BMCtot) at the
      distal end of the radius. Cylindrical specimens matched with those two sites were
      cut using a diamond circular saw, embedded in a polyester resin and subsequently
      submitted to two reference methods, nondestructive neutron activation analysis
      and flame atomic absorption spectrometry. Mineral contents measured by pQCT were
      closely correlated with those assessed by using the two reference methods, with
      correlation coefficients ranging from 0.862 to 0.960. The standard error of the
      estimate amounted 7-10% for the BMCc (junction of the middle and distal third),
      and 17-18% for the BMCtot (distal end). We conclude that pQCT is able to measure
      either cortical or total mineral content of the radius with a high degree of
      accuracy.

PMID- 8739906
TI  - Effect of age on the expression of insulin-like growth factor-I, interleukin-6,
      and transforming growth factor-beta mRNAs in rat femurs following marrow
      ablation.
AB  - The expression of insulin-like growth factor-I (IGF-I), interleukin-6 (IL-6), and
      transforming growth factor-beta 1 (TGF-beta 1) mRNA in rat femurs was examined
      following marrow ablation. Northern blot analysis showed multiple transcripts of
      IGF-I, a major transcript of 1.3 kb and a minor one of 2.4 kb for IL-6 and a
      single band of 2.5 kb for TGF-beta 1, respectively. Examination of the temporal
      activation pattern showed IGF-I expression peaked at day 3 (150% over the basal
      level) after injury and preceded the maximal expression of procollagen alpha
      1(I), osteopontin, alkaline phosphatase, and osteocalcin mRNAs. This suggests
      that IGF-I is involved mainly in osteoblast development and bone formation. In
      contrast, IL-6 expression was elevated between days 3 and 9 (45-60% over the
      basal level). The sustained elevation of IL-6 expression at day 9 is consistent
      with the role for this cytokine in the development of osteoclasts and bone
      resorption. The expression of TGF-beta 1 was not altered up to day 9 after marrow
      ablation. While the temporal expression patterns of IGF-I and IL-6 mRNA did not
      differ between adult and old rats, the maximal level of IGF-I mRNA at day 3 was
      72% higher in adult as compared to old bones. In contrast, the peak level of IL-6
      mRNA at days 6-9 was 45% higher in old as compared to adult bones. Although the
      level of TGF-beta 1 mRNA did not change following marrow ablation, levels of TGF
      beta 1 were consistently higher in old rats. Our results suggest that the
      impaired bone formation and elevated bone resorption in aged animals may be due
      in part to the reduced expression of IGF-I and an overexpression of IL-6 in old
      bone.

PMID- 8739907
TI  - Bone marrow capacity for bone cells and trabecular bone turnover in immobilized
      tibia after sciatic neurectomy in mice.
AB  - Trabecular bone turnover and bone marrow capacity for the development of bone
      cells in the tibia were assessed after sciatic neurectomy (NX) in mice. The right
      hindlimbs of 6-week-old DDY mice were neurectomized and left hindlimbs were sham
      operated and served as NX controls. Histomorphometrical analyses of the
      trabecular bone of the proximal tibia demonstrated the initial decrease in bone
      formation rate for the first 14 days and the subsequent increase in osteoclast
      surface for the next 14 days. The number of adherent stromal cells per tibia
      obtained for the NX limbs was reduced on days 7 and 10 postsurgically, and then
      recovered on day 12. However, the alkaline phosphatase activity of the cells was
      persistently depressed. The formation of osteoclast-like multinucleated cells in
      the marrow cultures obtained from NX limbs at days 10, 12, and 14 showed a
      significant increase in the medium containing parathyroid hormone (PTH). The
      number of colonies cultured for colony forming units-fibroblastic (CFU-f) that
      developed from the marrow cells did not differ in the NX and the contralateral
      limbs at any time during the period. On the other hand, the number of colonies
      cultured of colony forming units for granulocytes and macrophages (CFU-GM) was
      markedly increased for both the NX and the contralateral tibiae at days 12 and
      14. This study clearly demonstrates that there are two stages in the development
      of osteopenia after NX. During the first 14 days, trabecular bone formation and
      number of marrow stromal cells are reduced. In the second 14 day period, the
      trabecular osteoclast number is increased and osteoclast formation from the bone
      marrow cells is enhanced in the presence of PTH. However, neither the CFU-f nor
      the CFU-GM assay could identify the changes in osteogenic or osteoclastogenic
      potential of the bone marrow. These in vitro assays provide limited information
      on the shifts in bone marrow cell lineages and the local environment producing
      osteopenia in the immobilized limb in vivo.

PMID- 8739908
TI  - Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture: a
      three year follow-up study.
AB  - We have previously shown that elderly women with an increased serum
      undercarboxylated osteocalcin (ucOC) level have an increased risk of sustaining a
      hip fracture as compared to those with normal serum ucOC. We reassessed our
      findings on a larger number of hip fractures that occurred over 3 years in 183
      institutionalized women (aged 70-97 years) belonging to a large prospective
      clinical trial. Total OC, carboxylated OC, ucOC, and alkaline phosphatase were
      significantly higher at baseline in those who sustained a hip fracture during the
      follow-up. The age-adjusted odds ratio for hip fracture was three times higher in
      women with increased ucOC at baseline (odds ratio = 3.1, 99.9% C.I. = 1.7-6.0, p
      < 0.001). In the logistic regression, ucOC was still predictive of the hip
      fracture when age and parathyroid hormone concentration were included into the
      model (odds ratio = 2.6, 95% C.I. = 1.05-6.4). These data confirm that ucOC is a
      marker of the increased risk of hip fracture in elderly institutionalized women.
      Serum ucOC may reflect some nutritional deficiency associated with increased bone
      fragility.

PMID- 8739910
TI  - Insulin-induced activation of phosphoinositide 3-kinase in Fao cells.
AB  - Phosphoinositide 3-kinase (PI3-kinase) plays a crucial role in insulin signal
      transduction. We studied the molecular mechanism of the insulin-induced
      activation of PI3-kinase in rat hepatoma Fao cells using an antibody against the
      110-kDa catalytic subunit (p110) and two against the 85-kDa regulatory subunit
      (p85 alpha). PI3-kinase activity increased 1.6-fold in anti-p85
      immunoprecipitates after insulin stimulation, whereas it did not increase when
      cell lysates were first immunoprecipitated with anti-phosphotyrosine or anti
      insulin receptor substrate-1 (IRS-1), then with anti-p85, suggesting that the PI3
      kinase which associates with tyrosyl phosphoproteins including IRS-1 is
      responsible for the increase in kinase activity. The activated PI3-kinase
      molecules constituted 4-6% of the total PI3-kinase, and their specific activity
      was 11-14 times higher than that of the basal state. Anti-p110 recognized the
      catalytically active form of p110, and immunoprecipitated p110 only after
      exposure to insulin. Hence, the epitope of anti-p110, P200-C215, seems to be
      included in the portion of p110, the conformation of which is changed by insulin
      stimulation. We conclude that, in response to insulin stimulation, only a small
      fraction of p85 in the PI3-kinase pool associates with tyrosyl phosphoproteins
      including IRS-1, and that the specific activity of p110 is increased presumably
      through a conformational change including the P200-C215 region.

PMID- 8739909
TI  - Sulphonylurea treatment of NIDDM patients with cardiovascular disease: a mixed
      blessing?
AB  - Non-insulin-dependent diabetic (NIDDM) patients show a high incidence of
      cardiovascular disease, with greater risk of recurrent myocardial infarction and
      a less favourable clinical outcome than non-diabetic patients. The majority of
      NIDDM patients are treated with sulphonylurea (SU) derivatives. In the 1970's the
      University Group Diabetes Program concluded that tolbutamide treatment caused
      increased cardiovascular mortality; the study, which led to curtailment of oral
      antidiabetic treatment in the USA, was received with scepticism in Europe. Later
      criticism of its methodology reduced the impact of the study; however, the
      question of the safety of SU in NIDDM patients with cardiovascular disease has
      been re-opened in the face of new experimental data. The heart and vascular
      tissues do have prerequisites for SU action, i.e. SU receptors and ATP-dependent
      K+ (K+ATP) channels. These channels play an important role in the protection of
      the myocardium against ischaemia-reperfusion damage, and their closure by SU
      could lead to amplified ischaemic damage. Here we review evidence from animal and
      human studies for deleterious SU effects on ischaemia-induced myocardial damage,
      either by direct action or through diminished cardioprotective preconditioning.
      Closure of K+ATP channels by SU can lead to reduction of post-infarct
      arrhythmias; the drug has also been claimed to improve various atherosclerosis
      risk factors. The evidence for these beneficial effects of SU is also reviewed.
      We look at the major difficulties that hamper transfer of information from
      experimental studies to clinical decision-making: a) The affinity of SU for heart
      K+ATP channels is orders of magnitude lower than for beta-cell channels; is it
      reasonable to expect in vivo cardiac effects with therapeutic 'pancreatic' SU
      doses? b) Most studies utilized high doses of acutely administered SU; are
      effects similar in the chronic steady-state of the SU-treated diabetic patient?
      c) Convincing SU effects have been demonstrated in acutely induced ischaemia by
      acutely administering the drug; do such effects persist in the clinical situation
      of gradually progressive ischaemia? d) Ischaemia and modification of K+ATP
      channel activity induce complex events, some with opposing effects; what is the
      net result of SU action, and do different SU derivatives lead to different
      outcomes? e) In the chronic (and hence clinically relevant) situation, how can
      direct (deleterious or beneficial) SU effects be separated from beneficial
      effects mediated by the metabolic action of the drug? Only large prospective
      clinical studies, making use of advanced technology for assessment of
      cardiovascular function, can answer these questions. Millions of NIDDM patients
      are treated with SU derivatives; many are in the age group where cardiovascular
      risks are extremely high. The question of whether SU derivatives are beneficial
      or deleterious for these patients must finally be settle unequivocally.

PMID- 8739911
TI  - Xenografts of porcine islets immunoprotected in hollow fibres reduce the
      incidence of diabetes in non-obese diabetic mice.
AB  - Non-obese diabetic (NOD) mice develop an autoimmune disease with a long prodromal
      period and constitute a model for investigating the prevention of human insulin
      dependent diabetes mellitus. Since insulin injected prophylactically has been
      shown to reduce incidence of diabetes in NOD mice, we tested a new strategy
      consisting of prophylactic xenografts of porcine pancreatic islets
      immunoprotected in semipermeable hollow fibres. Female NOD mice were transplanted
      twice (at 60 and 180 days of age) with islet-containing or empty fibres. Within
      the group grafted with protected islets, the incidence of diabetes was reduced
      (37 vs 75%; p < 0.01), the onset of disease was delayed (p < 0.02), and the
      severity of lymphocytic inflammation of endogenous islets was reduced (p < 0.02).
      When already diabetic mice were not taken into account for analysis, blood
      glucose level was slightly lower in those grafted with islet-containing fibres (p
      < 0.04). Graft function was also evidenced by HPLC separation of porcine insulin
      in NOD sera. Histological and perifusion studies of fibres retrieved from
      recipients confirmed immunoprotection. During co-transfer, T splenocytes from
      mice grafted with islet-containing fibres were able to reduce the capacity of T
      cells from diabetic donors to adoptively transfer the disease (p < 0.01).
      Antigens for islet-cell autoantibodies (ICA) in pancreata from both groups were
      compared by immunofluorescence with the same ICA-positive human sera to ensure
      that differences were due to antigen quantitative changes. These antigens, which
      could serve as an index of a possibly more extensive antigen beta-cell rest, were
      decreased (p < 0.01) in mice grafted with protected islets. Reduction of diabetes
      and insulitis following early islet transplantation may thus be due to generation
      of cellular mechanisms that actively suppress disease, and possibly in part to a
      decrease in antigens which make beta cells less vulnerable to autoimmune
      aggression. These effects can be obtained with xenogeneic islets protected in
      hollow fibres, thereby eliminating the need for immunosuppression. Based on the
      concept of prophylactic insulin therapy, this form of insulin administration
      offers a controlled means of delivering insulin to meet the physiological needs
      of recipients.

PMID- 8739912
TI  - Cytokine-induced apoptotic cell death in a mouse pancreatic beta-cell line:
      inhibition by Bcl-2.
AB  - Cytokines are thought to contribute to the induction of pancreatic beta-cell
      destruction in insulin-dependent diabetes mellitus. The molecular mechanisms that
      underlie beta-cell death were investigated by studying cytokine-induced cell
      death in beta-cell lines. A combination of three cytokines (interleukin-1 beta,
      tumour necrosis factor-alpha, and interferon-gamma) induced apoptotic cell death
      in the mouse pancreatic beta-cell line beta TC1, as judged from the appearance of
      cells with hypodiploid nuclei and oligonucleosomal DNA fragmentation. The same
      treatment also induced apoptosis in the mouse pancreatic alpha-cell line alpha
      TC1 and the NOD/Lt mouse beta-cell line NIT-1, although to a lesser extent than
      in beta TC1 cells. The abundance of endogenous Bcl-2 in beta TC1 cells was lower
      than that in the other two cell lines. Overexpression of human Bcl-2 in beta TC1
      cells partially protected them from cytokine-induced cell death. These results
      suggest that apoptosis may be responsible, at least in part, for cytokine-induced
      beta-cell destruction and that Bcl-2 prevents apoptosis in pancreatic islet
      cells.

PMID- 8739914
TI  - Beta-cell growth in adolescent and adult rats treated with streptozotocin during
      the neonatal period.
AB  - Regeneration of neonatal beta cells after subtotal streptozotocin (STZ)-induced
      destruction is incomplete but nevertheless leads to rapid remission of
      hyperglycaemia. To study the proliferative and functional capacity of regenerated
      beta cells in adolescent and adult rats after early beta-cell damage and to
      determine the time point after birth which is decisive for regeneration, beta
      cell growth and metabolic capacity were analysed in rats treated during the
      neonatal period with STZ (100 micrograms/g body weight) and studied over 3 to 20
      weeks. Using immunocytochemistry combined with morphometry we found that the
      regenerated beta cells continue to increase in number till week 6 of life, when
      they reached values of more than 50% of those of controls. After week 6, the
      regenerated beta cells had enlarged in size but failed to further increase their
      number, although their proliferative activity, determined by bromodeoxyuridine
      (BrdU) pulse labelling, was still higher at 6 and 10 weeks than that of normal
      rats. The inability of regenerated beta cells to further increase their number
      coincided with a deterioration of their function (week 10, male rats; week 20,
      female rats). When beta cells were destroyed on day 2 or 5 instead of the day of
      birth, regeneration of beta cells markedly decreased and the rats were already on
      the threshold of development of glucose intolerance at 3 weeks of age. We
      concluded that the partially regenerated beta-cell population in rats treated
      with STZ on the day of birth ceases to grow 10 to 20 weeks later. This growth
      arrest may be due to the sustained functional demand to which these beta cells
      are exposed in order to compensate for their reduced number. Beta-cell capacity
      for regeneration declines rapidly during the first days of life.

PMID- 8739913
TI  - Cultured retinal capillary pericytes die by apoptosis after an abrupt fluctuation
      from high to low glucose levels: a comparative study with retinal capillary
      endothelial cells.
AB  - A number of clinical observations concerning cases of glycemic fluctuation have
      prompted us to study whether or not a rapid change in blood glucose concentration
      can aggravate retinal microvascular pathology during the early stage of diabetic
      retinopathy. We conducted a comparative study of retinal capillary pericytes and
      endothelial cells in vitro. Both types of cells, either in single culture or in
      co-culture, were initially incubated in medium with high glucose (20-40 mmol/l),
      followed by a rapid reduction of glucose to 3.5, 1, or 0.5 mmol/1. This type of
      reduction of extracellular glucose resulted in depletion of intracellular
      glucose, occurring much faster in pericytes than in endothelial cells. The abrupt
      reduction in glucose caused pericyte cell shrinkage and nuclear condensation
      associated with DNA fragmentation, followed by loss of cell viability. All of
      these pericyte changes are apoptosis-like characteristics. This apoptotic process
      was prevented by the addition of cycloheximide, a protein synthesis inhibitor, or
      by platelet-derived growth factor BB, which is known competent factor for
      pericyte growth. In analysis of signalling pathways during the abrupt fluctuation
      of glucose, the occurrence of pericyte apoptosis was an intracellular calcium
      dependent, protein kinase C and protein kinase A mediated, and poly (ADP-ribose)
      synthetase-dependent process. Interestingly, a larger degree of DNA fragmentation
      was observed with a higher magnitude and a longer duration of pre-existing
      hyperglycaemia. These results suggest that the magnitude and duration of pre
      existing hyperglycaemia prime the apoptotic responsiveness of pericytes. Retinal
      capillary endothelial cells, after an identical glucose fluctuation treatment did
      not undergo an apoptotic process.

PMID- 8739915
TI  - Expression of a dominant-negative Ras mutant does not affect stimulation of
      glucose uptake and glycogen synthesis by insulin.
AB  - It has previously been shown that insulin-induced stimulation of glucose uptake
      and glycogen synthesis requires activation of phosphatidylinositol-3-kinase
      (PI3kinase). Insulin also induces formation of RasGTP in cells and various
      studies have yielded inconsistent data with respect to the contribution of
      signalling pathways activated by RasGTP, to insulin-stimulated glucose uptake and
      glycogen synthesis. We have examined the requirement of RasGTP-mediated
      signalling for these insulin responses by expression of a dominant negative
      mutant of Ras (RasN17) in cells by vaccinia virus mediated gene transfer. This
      Ras-mutant abrogates the signalling pathways mediated by endogenous RasGTP.
      Subsequently, the ability of insulin to stimulate 2-deoxyglucose uptake and
      glycogen was examined. We observed that expression of RasN17 in 3T3L1 adipocytes
      did not affect the stimulation of hexose uptake by insulin. Similarly, expression
      of RasN17 in A14 cells, an NIH 3T3-derived cell line with high expression of
      insulin receptors, did not affect insulin-induced stimulation of glycogen
      synthesis. In both cell lines, insulin-induced phosphorylation of Mapkinase
      (Erk1,2) was abrogated after expression of RasN17, demonstrating the functional
      interference by RasN17 with signalling mediated by endogenous RasGTP. Wortmannin,
      an inhibitor of PI3kinase, abolished dose-dependently the insulin-induced
      stimulation of hexose uptake and glycogen synthesis without an effect on RasGTP
      levels in both cell types. We conclude that stimulation of glucose transport and
      glycogen synthesis by insulin occurs independently of RasGTP-mediated signalling.

PMID- 8739916
TI  - Alterations in the ultradian oscillations of insulin secretion and plasma glucose
      in aging.
AB  - Normal insulin secretion includes oscillations with a period length of 80-150 min
      which are tightly coupled to glucose oscillations of similar period. To determine
      whether normal aging is associated with alterations in these ultradian
      oscillations, eight, modestly overweight, older men (65 +/- 5 years) and eight
      weight-matched young control subjects (25 +/- 4 years) were studied during 53 h
      of constant glucose infusion. Blood samples were collected every 20 min and
      insulin secretion rates were calculated by deconvolution. Ultradian oscillations
      of glucose and insulin secretion were evident in both groups. Pulse frequency was
      similar for glucose and insulin secretion, and was not affected by age. The
      absolute amplitude of the glucose oscillations was similar in both groups but
      their relative amplitude was slightly dampened in the older adults. Both the
      absolute and the relative amplitudes of insulin secretory oscillations were
      markedly reduced in the older subjects. The normal linear increase in the
      amplitude of insulin oscillations occurring with increasing amplitudes of glucose
      oscillations was still present in the older adults but analysis of covariance
      indicated that the slope was significantly lower than in the young control
      subjects (p < 0.0005), reflecting a decreased responsiveness of the beta cell to
      glucose changes. The temporal concordance between insulin and glucose
      oscillations, as estimated by pulse concomitancy and cross-correlation, was also
      lower in older subjects. The similarities between the alterations in the
      ultradian oscillations of insulin secretion and glucose in older healthy adults
      and those occurring in diabetic patients suggest that an impairment of beta-cell
      function may play a primary role in the deterioration of glucose tolerance in
      aging.

PMID- 8739917
TI  - Poor physical fitness, and impaired early insulin response but late
      hyperinsulinaemia, as predictors of NIDDM in middle-aged Swedish men.
AB  - In a prospective population-based study of middle-aged Caucasian men, performed
      in Malmo, Sweden, specifically designed to evaluate physical fitness, early and
      late insulin response as predictors of non-insulin-dependent diabetes mellitus
      (NIDDM), 4,637 non-diabetic men underwent oral glucose tolerance tests at the
      ages of 48 and 54 years. At the baseline examination, physical fitness was
      measured in terms of lung vital capacity and oxygen uptake during ergometry;
      early insulin response in terms of the 40-min insulin increment during an oral
      glucose tolerance test (a correlate of acute insulin response to an intravenous
      glucose tolerance test), and late insulin response were measured in terms of the
      2-h insulin value during the oral glucose tolerance test (a correlate of glucose
      disposal during euglycaemic clamp testing). Of the subjects studied 116 developed
      NIDDM (0.4% annually), and when compared with non-diabetic men at baseline, they
      were found to have an 11% higher mean body mass index (p < 0.001), a higher
      frequency of family history of diabetes (31 vs 18%, p < 0.001), 16% lower mean
      physical activity index (p < 0.05), 16% lower mean estimated maximal oxygen
      uptake (p < 0.001), 10% lower mean vital capacity (p < 0.001), 26% lower 40-min
      to total insulin response ratio (p < 0.001), and a 2.7 times higher mean 2-h
      insulin value during an oral glucose tolerance test (p < 0.001). Regression
      analysis (using Cox's proportional hazards model) showed both low vital capacity,
      and impaired early insulin response but late hyperinsulinaemia to be independent
      predictors of NIDDM, in addition to body mass index and fasting blood glucose
      level (p = 0.05-0.0001). Among subjects with impaired glucose tolerance at
      baseline (44 of 278 developed NIDDM), fasting glucose level alone predicted
      diabetes in this model. The findings suggest that in this age group in a
      Caucasian population, not only does insulin resistance precede glucose
      intolerance and NIDDM, but also loss of early insulin response indicating
      impaired beta-cell function to be an early feature of the process culminating in
      diabetes. As both physical fitness [which correlates inversely with late insulin
      response (r= -0.42, p < 0.0001)], and the level of physical activity were shown
      to correlate with diabetes development in this large series, measures to correct
      these adverse features should be included in future strategies for preventing
      NIDDM.

PMID- 8739918
TI  - Effects of ingested fructose and infused glucagon on endogenous glucose
      production in obese NIDDM patients, obese non-diabetic subjects, and healthy
      subjects.
AB  - Increased endogenous glucose production (EGP) and gluconeogenesis contribute to
      the pathogenesis of hyperglycaemia in non-insulin-dependent diabetes mellitus
      (NIDDM). In healthy subjects, however, EGP remains constant during administration
      of gluconeogenic precursors. This study was performed in order to determine
      whether administration of fructose increases EGP in obese NIDDM patients and
      obese non-diabetic subjects. Eight young healthy lean subjects, eight middle-aged
      obese NIDDM patients and seven middle-aged obese non-diabetic subjects were
      studied during hourly ingestion of 13C fructose (0.3 g.kg fat free mass-1.h-1)
      for 3 h. Fructose failed to increase EGP (measured with 6,6 2H glucose) in NIDDM
      (17.7 +/- 1.9 mumol.kg fat free mass-1.min-1 basal vs 15.9 +/- 0.9 after
      fructose), in obese non-diabetic subjects (12.1 +/- 0.5 basal vs 13.1 +/- 0.5
      after fructose) and in lean healthy subjects (13.3 +/- 0.5 basal vs 13.8 +/- 0.6
      after fructose) although 13C glucose synthesis contributed 73.2% of EGP in lean
      subjects, 62.6% in obese non-diabetic subjects, and 52.8% in obese NIDDM
      patients. Since glucagon may play an important role in the development of
      hyperglycaemia in NIDDM, healthy subjects were also studied during 13C fructose
      ingestion + hyperglucagonaemia (232 +/- 9 ng/l) and during hyperglucagonaemia
      alone. EGP increased by 19.8% with ingestion of fructose + glucagon (p < 0.05)
      but remained unchanged during administration of fructose or glucagon alone. The
      plasma 13C glucose enrichment was identical after fructose ingestion both with
      and without glucagon, indicating that the contribution of fructose
      gluconeogenesis to the glucose 6-phosphate pool was identical in these two
      conditions. We concluded that during fructose administration: 1) gluconeogenesis
      is increased, but EGP remains constant in NIDDM, obese non-diabetic, and lean
      individuals; 2) in lean individuals, both an increased glucagonaemia and an
      enhanced supply of gluconeogenic precursors are required to increase EGP; this
      increase in EGP occurs without changes in the relative proportion of glucose 6
      phosphate production from fructose and from other sources (i.e. glycogenolysis +
      gluconeogenesis from non-fructose precursors).

PMID- 8739919
TI  - Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria.
      The Microalbuminuria Captopril Study Group.
AB  - In insulin-dependent diabetes mellitus (IDDM), microalbuminuria predicts renal
      and cardiovascular disease. We report a combined analysis of 235 normotensive
      IDDM patients with microalbuminuria who participated in two 24-month double
      blind, randomised, placebo-controlled trials to assess the effects of captopril
      50 mg twice daily on the progression to overt clinical albuminuria. Of the 225
      patients who were evaluable on an intent to treat basis, 25 of 114 placebo
      treated patients (21.9%) and 8 or 111 captopril-treated patients (7.2%)
      progressed to persistent clinical albuminuria. The risk of progression over 24
      months was significantly reduced by captopril (p = 0.004) with a risk reduction
      of 69.2% (95% confidence interval (CI):31.7 to 86.1%). This degree of risk
      reduction remained at the same level (62.9% [16.1-83.6%], p = 0.017) after
      adjustment for differences in time-varying mean arterial blood pressure. Albumin
      excretion rate increased by an average of 14.2% [3.1-26.5%] per year in the
      placebo-treated group compared with a reduction of 9.6% [-18.6-0.4%] per year in
      the captopril-treated group (p = 0.002). The rate of fall of creatinine clearance
      tended to be faster in the placebo-treated group than in the captopril-treated
      group (-6.4 [-10.2- -2.5] vs -1.4 [-5.3-2.6] ml.min-1.1.73m-2, p = 0.07).
      Baseline albumin excretion rate (p < 0.0001) and glycated haemoglobin (p = 0.03)
      were independent predictors of progression to clinical albuminuria and changes in
      mean arterial blood pressure (p = 0.02) and serum cholesterol level (p = 0.003)
      were significantly associated with percentage changes in albumin excretion rate.
      Captopril reduces the risk of progression to overt nephropathy in IDDM patients
      with microalbuminuria, an effect partly independent of its blood pressure
      lowering effects.

PMID- 8739920
TI  - Diabetes susceptibility at IDDM2 cannot be positively mapped to the VNTR locus of
      the insulin gene.
AB  - An inconsistency has come to light between the conclusion of Lucassen et al. that
      IDDM2 (11p15.5) must lie within a 4.1 kilobase (kb) segment at the insulin (INS)
      locus and their own data showing statistically significant associations between
      insulin-dependent diabetes mellitus (IDDM) and markers beyond the boundaries of
      that segment. We present data from an independent study of 201 IDDM patients and
      107 non-diabetic control subjects that also show significant association with a
      marker 5' of the INS locus. Patients and control subjects were genotyped at INS/+
      1140 A/C (a surrogate for the variable number tandem repeat (VNTR) polymorphism
      in the regulatory part of the INS gene) and a marker 5' of the tyrosine
      hydroxylase (TH) gene, TH/pINS500-RsaI, making it 10 kb 5' of the VNTR.
      Homozygotes for INS/ + 1140 allele '+' were significantly more frequent among
      IDDM patients than among control subjects (73 vs 45%, p < 0.001) giving an odds
      ratio of 3.3 (95% confidence interval (CI): 2.0-5.3). A very similar association
      was found for homozygotes for the TH/RsaI allele '+' (53 vs 31%, p < 0.001)
      giving an odds ratio of 2.6 (95%CI 1.6-4.2). By multilocus analysis, the TH/RsaI
      allele '+' identified a subset of INS/ + 1140 alleles '+' haplotypes that are
      more specifically associated with IDDM (odds ratio = 5.4, 95%CI 2.9-10.4) than
      allele + 1140 '+' as a whole. In conclusion, the segment of chromosome 11 that is
      associated with IDDM spans, at least, the INS and TH loci. No legitimate claim
      can be made that IDDM2 corresponds to the VNTR polymorphism at the INS locus
      until the correct boundaries for IDDM2 have been defined and other loci within
      them have been excluded as determinants of IDDM.

PMID- 8739922
TI  - Does fall in tissue glucose precede fall in blood glucose?

PMID- 8739921
TI  - Molecular scanning of the insulin receptor substrate-1 (IRS-1) gene in Japanese
      patients with NIDDM: identification of five novel polymorphisms.
AB  - Since the insulin receptor substrate-1 (IRS-1) is the major substrate of the
      insulin receptor tyrosine kinase and has been shown to activate
      phosphatidylinositol (PI) 3-kinase and promote GLUT4 translocation, the IRS-1
      gene is a potential candidate for development of non-insulin-dependent diabetes
      mellitus (NIDDM). In this study, we have identified IRS-1 gene polymorphisms,
      evaluated their frequencies in Japanese subjects, and analysed the contribution
      of these polymorphisms to the development of NIDDM. The entire coding region of
      the IRS-1 gene of 94 subjects (47 NIDDM and 47 control subjects) was screened by
      polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP)
      analysis. Seven SSCP polymorphisms were identified. These corresponded to two
      previously identified polymorphisms [Gly971 --> Arg (GGG --> AGG) and Ala804 (GCA
      --> GCG)] as well as five novel polymorphisms [Pro190 --> Arg (CCC --> CGC),
      Met209 --> Thr (ATG --> ACG), Ser809 --> Phe (TCT --> TTT), Leu142 (CTT --> CTC),
      and Gly625 (GGC --> GGT)]. Although the prevalence of each of these polymorphisms
      was not statistically different between NIDDM and control subjects, the
      prevalence of the four IRS-1 polymorphisms with an amino acid substitution
      together was significantly higher in NIDDM than in control subjects (23.4 vs
      8.5%, p < 0.05), and two substitutions (Met 209 --> Thr and Ser809 --> Phe) were
      found only in NIDDM patients. Equilibrium glucose infusion rates during a
      euglycaemic clamp in NIDDM and control subjects with the IRS-1 polymorphisms
      decreased by 29.5 and 22.0%, respectively on the average when compared to those
      in comparable groups without polymorphisms, although they were not statistically
      significant. Thus, IRS-1 polymorphisms may contribute in part to the insulin
      resistance and development of NIDDM in Japanese subjects; however, they do not
      account for the major part of the decrease in insulin-stimulated glucose uptake
      which is observed in subjects with clinically apparent NIDDM.

PMID- 8739923
TI  - Can hypoglycaemia be predicted before its onset?

PMID- 8739925
TI  - Progress in surgery.

PMID- 8739924
TI  - Laboratory chow-induced insulin resistance: a possible contributor to autoimmune
      type 1 diabetes in rodents.

PMID- 8739926
TI  - Acute abdominal pain in adults.
AB  - The purpose of this prospective study was to elucidate the characteristics of
      adult patients with acute abdomen admitted to a Finnish university hospital. A
      total of 639 patients entered the study. The most common cause of acute abdomen
      was non-specific abdominal pain (NSAP) (33.0%) followed by acute appendicitis
      (23.3%) and acute biliary disease (8.8%). The male:female ratio was 47:53 in the
      whole study population, but there were differences in the age and sex
      distributions when studied by diagnosis. NSAP was mainly presented in young
      women, but also in patients over 75 years of age. Acute appendicitis was most
      frequently found in young men, and biliary disease was most common in elderly
      women. A male predominance was noted in cases of alcoholic pancreatitis and
      gastritis, renal stones and peptic ulcer. Young women and elderly patients were
      slightly over-represented in the study population when compared with the whole
      population residing within the study area. 43% of the patients were operated on,
      and surgery was most common in patients aged 55-64 years and 15-24 years.
      Altogether 15% of the patients were discharged without hospitalisation. Twelve
      patients (1.9%) died of various causes, the most common of which was malignancy
      (four patients). In conclusion, a considerably large proportion (one third) of
      cases with acute abdomen remained without any specific explanation. Further, age
      and gender seem to be important factors when the most probable cause of acute
      abdomen is to be considered. Operative treatment is necessary in almost half of
      cases, and mortality for acute abdomen is low.

PMID- 8739927
TI  - The outcome of elderly patients after operation for acute abdomen.
AB  - A retrospective analysis of 224 patients was carried out to evaluate the outcome
      of elderly patients after operation for acute abdominal pain. The mean (+/- SD)
      age of the patients was 74.6 (+/- 6.4) years (range 65-96) and the male/female
      ratio was 104/120. The most common causes for an emergency operation were acute
      biliary disease (26%), acute appendicitis (18%), gastrointestinal cancer (11%)
      and incarcerated hernia (10%). Twenty-nine patients (13%) died during the one
      month postoperative period. The most common causes of death were gastrointestinal
      cancer (24%), ischaemic heart disease (14%) and complicated peptic ulcer disease
      (14%). Ninety-two (41%) patients had non-lethal postoperative complications, the
      commonest of which were wound infection or dehiscence (28%), urinary tract
      infection (17%), and paralytic ileus (8%). Ten patients were reoperated on for
      postoperative complications. The mean hospitalization time was 12.5 days (range 1
      99). The results in the analysis of the long-term outcome (mean follow-up time 21
      months) revealed that 17% of the primarily survived patients had died. Living
      patients were satisfied with the treatment and only a few patients were
      institutionalised after surgery. We conclude that both the short-term and long
      term outcome of elderly patients after an emergency abdominal operation is good
      in benign diseases, and active surgery is justified.

PMID- 8739928
TI  - The effect of dextran infusion on antithrombin III concentrations and on platelet
      function during minor surgery.
AB  - The effects of dextran on the antithrombin (AT) III activity and blood
      coagulation, evaluated with thromboelastography, were investigated in 26 patients
      (anaesthesia risk class I or II) scheduled for minor surgery under general
      anaesthesia. In the Dextran group the patients were infused first with dextran 7
      ml/kg, then with Ringer's acetate. In the Ringer group, the patients received
      only Ringer's acetate. In the recovery room fluid therapy was continued with 5%
      dextrose in water until the first postoperative day. Blood loss and fluid
      replacement were comparable in the groups. Haematocrit (Hcr) decreased
      significantly in the Dextran group, and the platelet count decreased in both
      groups during surgery. The median baseline AT III values were similar in the
      study groups. In the recovery room, the median AT III value was lower in the
      Dextran than in the Ringer group, 78% and 92%, respectively (P < 0.05). By the
      following day, the AT III values had returned near the initial level. After
      surgery, the maximal amplitude of thromboelastogram was 48 mm in the Dextran
      group, and 58 mm in the Ringer group (P < 0.05). In conclusion, fluid replacement
      with dextran resulted in modest and short-lived alterations in blood coagulation.

PMID- 8739929
TI  - Cerebral haemorrhage after carotid endarterectomy.
AB  - Cerebral stroke is a serious complication related to carotid endarterectomy
      (CEA), being most frequently caused by thromboembolic events and less frequently
      on account of cerebral haemorrhage. The present series comprised five out of 857
      (0.6%) patients who had undergone CEA at Oulu University Hospital between the
      years 1974 and 1993 and suffered a postoperative stroke four to 13 days after
      surgery due to intracerebral haemorrhage (IH). Preoperatively, all these patients
      were neurologically intact, with transient ischaemic attacked (TIA) as the main
      indication for CEA. All five patients had a history of arterial hypertension
      treated adequately preoperatively, and one patient had high blood pressure levels
      after surgery. Critical ipsilateral stenosis of the internal carotid artery (>
      90%) was detected in the preoperative angiogram in all five cases. The primary
      outcome after CEA was uneventful in every case, without any signs of neurological
      deficiency. The symptoms, comprising severe headache, convulsions and/or
      hemiparesis occurred suddenly four to 13 days (mean seven days) after CEA. The
      diagnosis of IH was based on computed tomography (CT) findings. All five patients
      were treated conservatively. Three of them died. We conclude that even
      normotensive, neurologically intact patients without demonstrable cerebral
      infarction or postoperative hypertension may suffer cerebral haemorrhage after
      the relief of high-grade carotid stenosis. The role of possible insufficiency of
      the autoregulatory mechanisms of the cerebral vasculature on account of long
      standing critical stenosis of the internal carotid artery and subsequent
      uncontrolled hyperperfusion following CEA are discussed.

PMID- 8739930
TI  - Infrarenal aortofemoral bypass surgery: risk factors and mortality in 330
      patients with abdominal aortic aneurysm or aortoiliac occlusive disease.
AB  - 330 patients operated on for infrarenal abdominal aortic aneurysm (AAA) or
      aortoiliac occlusive disease (AIOD) between 1976-85 were retrospectively reviewed
      for early mortality and long-term survival. Data were analysed by crosstabulation
      and stepwise logistic regression methods for early mortality and by Kaplan-Meyer
      and Cox proportional hazard model for late survival. The 30-day mortality for
      elective AAA-patients was 9.6% and for ruptures 64.6%. For the AIOD-patients it
      was 2.0%. The principal cause of early death in the elective patients was acute
      myocardial infarction. The five-year survival rates for elective and ruptured AAA
      and AIOD-patients were 68%, 56% and 74%, respectively. The major late cause of
      death was coronary heart disease followed by pulmonary cancer. The risk factors
      for 30-day mortality were coronary heart disease, rupture, preoperative shock,
      excessive bleeding and aortic crossclamping time for the AAA-patients. In the
      rupture group the specialization of the surgeon had a significant impact on early
      mortality. Factors affecting the late survival were age, chronic cardiac failure,
      operation year, chronic pulmonary disease and previous malignancy in the whole
      study population. The late survival of both AAA and AIOD-patients after a
      successful operation was significantly shorter than that of an age- and
      sexmatched normal population. The late survival of AAA-patients was worse than
      that of AIOD-patients.

PMID- 8739931
TI  - Nonsuture end-to-end microvascular anastomosis using intravascular stents.
AB  - The objective of this report is to describe a new method of nonsuture end-to-end
      microvascular anastomosis. The vessels to be anastomosed are prepared separately
      before division by inserting a cylinder-shaped intravascular stent into each
      vessel. The anastomosis is completed after dividing the vessels. The vessels
      containing the stents are approximated. The anastomosis is then performed by
      sliding the stents into each other and is kept together by the force of friction.
      The method was used for anastomosing the aorta, end to end, in seven rats. The
      rats survived for one to 25 days with a radiological patient aorta and a fibrous
      healing of the vessels. This method has a potential use for microvascular
      anastomosis.

PMID- 8739932
TI  - De Vega's annuloplasty for tricuspid regurgitation.
AB  - A total of 337 patients underwent a mitral or combined mitral and aortic valve
      operation at the Oulu University Hospital between 1986 and 1992. Of these, 30
      (8.9%) patients had De Vega's semicircular annuloplasty performed because of
      tricuspid regurgitation (TR) which was considered functional in nature. There
      were five (16.6%) early and seven (23.3%) late deaths during the follow-up period
      of 10 to 71 months. The preoperative mean New York Heart Association (NYHA)
      functional class was 3.4, and at follow-up 13 (76.5%) of the survivors were in
      NYHA CLass I or II. The actuarial survival rate was 37.6% at five years. All the
      survivors were evaluated echocardiographically and the TR was considered mild in
      56.3%, moderate in 25.0% and severe in 18.7% of the cases. Tricuspid annuloplasty
      using De Vega's semicircular suture technique is a simple and effective procedure
      in patients with mild to moderate regurgitation. In patients with massive
      regurgitation, which is usually associated with a massively dilated tricuspid
      annulus and pulmonary hypertension, annuloplasty should be reinforced using a
      ring technique. Tricuspid valve replacement is hardly ever needed in the
      treatment of functional tricuspid regurgitation.

PMID- 8739933
TI  - Low myocardial temperatures are associated with postoperative conduction defects
      after coronary artery bypass surgery.
AB  - The incidence and significance of postoperative conduction defects after coronary
      artery bypass surgery were investigated prospectively in 181 patients. Several
      pre- and perioperative variables, especially the temperature in three regions of
      the myocardium, were recorded as explanatory variables. The incidence of
      conduction defect(s) in the immediate postoperative electrocardiogram (ECG) was
      55.8%, and 35.9% of the patients had a conduction defect when leaving hospital.
      Two patients had a permanent third degree atrioventricular (AV) block. Five
      pacemakers were implanted. Left main coronary artery stenosis was more common (P
      < 0.01), and the perioperative myocardial temperatures (P < 0.05-0.01) were lower
      in patients with conduction defects. These patients had also low postoperative
      cardiac output more often (P < 0.001), their creatine kinase myocardial (MB)
      fraction values were higher (P < 0.01), and they stayed in hospital longer (P <
      0.05). Right bundle branch block had no significant association with the studied
      variables.

PMID- 8739934
TI  - Procaine and timing of aortic declamping affect ventricular reperfusion
      fibrillation.
AB  - Both ventricular fibrillation and electric defibrillation are detrimental to the
      myocardium. Therefore, we studied the effect of procaine hydrochloride during
      crystalloid cardioplegia and the effect of performing all central anastomoses
      before aortic declamping in an attempt to prevent ventricular reperfusion
      fibrillation during coronary bypass operation. Seventy-four patients were
      randomised, first to receive procaine hydrochloride or saline during
      cardioplegia, and secondly, to have central anastomoses performed before and
      after aortic declamping. In patients receiving procaine in cardioplegic solution
      (n = 37), the mean ventricular fibrillation time was shorter (27 +/- 79 sec. vs
      205 +/- 161 sec., P < 0.0001), the proportion of patients spontaneously achieving
      stable rhythm was higher (67.6% vs 13.5%, P < 0.0001) and the mean number of
      defibrillations was lower (0.3 +/- 0.7 vs 2.4 +/- 1.7, P < 0.0001) than in
      patients receiving placebo (n = 37). Although the aortic occlusion time was
      longer (112 +/- 28 min vs 91 +/- 26 min, P = 0.0015) in patients with central
      anastomoses made during cardiac arrest (n = 35) and the mean fibrillation time
      was shorter (53 +/- 87 sec. vs 173 +/- 179 sec., P = 0.0006) than compared with
      patients with central anastomoses made after declamping the aorta (n = 39), the
      mean number of defibrillations (1.2 +/- 1.7 vs 1.4 +/- 1.7, P = 0.59) and the
      cardiopulmonary bypass time (138 +/- 29 min vs. 132 +/- 34 min, P = 0.47) were
      not statistically different between these groups. There were no differences in
      arrhythmias, conduction defects or postoperative recovery between the study
      groups. We conclude that both procaine hydrochloride during cardioplegia and the
      performance of central anastomoses of vein grafts during aortic occlusion
      effectively reduce reperfusion ventricular fibrillation.

PMID- 8739935
TI  - Operative treatment of thoracic outlet syndrome in Finland.
AB  - The data from the nationwide hospital discharge register was used for collecting
      the diagnoses of the thoracic outlet syndrome (TOS) which were combined with the
      procedure numbers of first rib resection and scalenotomy. During the years 1987
      1993 the total number of operative operative periods for patients with a TOS
      diagnosis was 483 for 464 patients. Each year first rib resections were done
      significantly (P = 0.001) more often (55.7 SE 7.1; 1.11/100,000) than
      scalenotomies (13.4 SE 1.8; 0.27/100,000). The operation for TOS was most
      commonly combined with the diagnosis of TOS with brachial plexus lesion in 53%,
      TOS NUD (not classified) in 21%, TOS with subclavian artery compression in 19%,
      with a cervical rib in 4% and TOS with venous compression in 3%. The large
      proportion of the diagnosis TOS NUD clearly shows the need for a better
      definition for the TOS diagnosis. As long as clear diagnostic criteria are
      lacking, the division of TOS into subgroups is arbitrary. Diagnostic division
      into true neurogenic, major arterial and venous TOS, and classifying the rest of
      the TOS diagnoses under TOS NUD or cervicobrachiale diffusum is recommended.

PMID- 8739936
TI  - Return to work after posterolateral fusion with transpedicular instrumentation
      for spondylarthrosis of the lumbosacral spine.
AB  - We reviewed 41 working-age adults with lumbosacral spondylarthrosis treated by
      posterolateral spinal fusion using transpedicular instrumentation. The fusion
      indication was a long-standing, intractable low-back and/or radiating pain,
      resistant to conservative treatment, without any radiological evidence or disc
      herniation or spinal stenosis. All patients were evaluated for their post
      treatment employment status. The patients were followed up until they had either
      returned to work or received a permanent disability pension. Only 15 patients out
      of 41 returned to work after an average postoperative sick leave of seven months.
      A proper selection of patients is mandatory when this kind of resource-consuming
      spinal surgery is practised.

PMID- 8739937
TI  - A prospective controlled trial of the fracture of the humeral medial epicondyle-
      how to treat?
AB  - Twenty-one patients, 11 male and nine female, with fracture of medial humeral
      epicondyle were treated. The mean age of the patients was 21 (range 8-52) years.
      The average initial displacement was 13 (range 3-24) mm, and four out of 21
      patients had a dislocation of the elbow joint. Two patients were first treated
      conservatively, but later on operation for removal of the non-united fragment and
      reattachment of the ligaments and muscles was necessary. One patient was treated
      by primary excision of the fragment. Eighteen patients were treated by open
      reduction and internal fixation using self-reinforced polyglyclycolide (SR-PGA)
      screws in five patients, poly-l-lactide (SR-PLLA) screw in one, small (SR-PGA)
      rods in seven and Kirschner-wires in five patients. Solid union took place in 14
      out of 18 patients and a good stability of the elbow joint was achieved. Fifteen
      patients scored an excellent result according to the scale of Broberg and Morrey.
      Although this series was not randomly allocated in respect of the method of
      treatment, it shows that medial epicondylar fractures can be fixed with
      absorbable implants without any need for removal procedure.

PMID- 8739938
TI  - Primary and secondary Charnley-Hastings hemiarthroplasty in displaced femoral
      neck fractures and their sequelae.
AB  - 298 women and 36 men, median age 80 (range 40-95) years with 340 femoral neck
      fractures were treated with Charnley-Hastings hemiarthroplasty and followed for
      41 (range 12-86) months. 107 replacements were primary because of poor reduction
      and 233 were secondary, performed during 60 months after the injury because of
      disturbed fracture healing. The results of primary and secondary replacements
      regarding morbidity, mortality, prosthesis failure and survival were similar. The
      major postoperative complications were: early wound infection (10 cases, 2.9%),
      dislocation of the prosthesis (16 cases, 4.7%), fracture of femoral shaft (nine
      cases, 2.7%), and loosening of components with reoperation (six cases, 1.8%). In
      total 33 reoperations (9.7%) were performed. When failure of the prosthesis was
      defined as dislocation, fracture or removal of part or whole prosthesis, the
      three-year and six-year survival rates were 89 and 80%, respectively. Defining
      the failure as removal of prosthesis component(s) only, the success rates were 96
      and 94%, respectively. We conclude that cemented bipolar prosthesis offers a good
      alternative for salvage of displaced or failed femoral neck fracture.

PMID- 8739939
TI  - A five to seven years follow-up of 102 cementless Synatomic knee arthroplasties.
AB  - One hundred and two cementless Synatomic total knee prostheses were implanted in
      our hospital between January 1987 and October 1989. All knees were
      retrospectively followed up for five to seven years and examined for both pre-
      and postoperative clinical or radiological factors indicating aseptic loosening.
      The overall survival of the implants was 88.6%. The mean preoperative
      tibiofemoral angle of 178.5 degrees was found to be corrected immediately
      postoperatively to 183.4 and at the latest review to 182.3 degrees, with a slight
      shift towards varus which in the case of femoral component further increased
      during follow-up (P < 0.05). No correlation was found between tibiofemoral
      alignment and overall joint survival. Improvement of the preoperative marked
      (over 12 degrees) tibiofemoral valgus alignment correlated to clinical failure (P
      < 0.05). No such correlation was observed in pronounced varus knees (P = 0.897).
      A clear correlation was observed between the clinical outcome and the knee joint
      (P < 0.05) and function (P < 0.05) scores. Especially pain correlated closely
      with survival.

PMID- 8739940
TI  - Transfusion needs in hip and knee arthroplasty.
AB  - A 12 months retrospective study of cross-match and transfusion practice in hip
      and knee arthroplasty in a general orthopaedic unit was carried out aiming to
      assess the transfusion needs for these procedures prior to enrolling future
      patients in a pre-donation program for autologous transfusion. The study revealed
      acceptable transfusion practice in the unit. For both procedures, over 75% of all
      transfusions were carried out in the peri-operative period. Eighty-nine percent
      of patients undergoing hip arthroplasty required transfusion with a maximum of
      three units, while a maximum of only two units were needed to meet the
      transfusion requirements of 86% of patients undergoing knee arthroplasty. In hip
      arthroplasty, the overall transfusion index (Ti), was 2.05, and this value did
      not vary significantly according to preoperative haemoglobin values. This was in
      contrast to knee arthroplasty, where the Ti was 2.9 in patients with preoperative
      haemoglobin value less than 11 g/dL compared to only 0.6 for haemoglobin value
      greater than 13 g/dL. In conclusion, in an autologous transfusion program, the
      availability of three units would satisfy the transfusion needs in 89% of hip
      arthroplasties, while the availability of two units would satisfy the needs in
      86% of knee arthroplasties. Preoperative donation for knee arthroplasty with a
      haemoglobin level over 13 g/dL may prove wasteful as in our current practice, the
      transfusion index in this group of patients was only 0.6.

PMID- 8739941
TI  - Pernicious anaemia and hypoparathyroidism in a patient with Kearns-Sayre syndrome
      with mitochondrial DNA duplication.

PMID- 8739942
TI  - Fatal neonatal liver failure and depletion of mitochondrial DNA in three children
      of one family.

PMID- 8739943
TI  - A mitochondrial DNA microdeletion in a newborn girl with transient lactic
      acidosis.

PMID- 8739944
TI  - Clinical variability associated with the mutation at nucleotide position 8344 of
      the mitochondrial DNA.

PMID- 8739945
TI  - Functional mtDNA replication defect in a fibroblast line from a patient with
      mtDNA depletion.

PMID- 8739946
TI  - Screening of mtDNA mutations in Italian LHON pedigrees.

PMID- 8739947
TI  - Decreased activity of the mitochondrial ATP-synthase in fibroblasts from children
      with late-infantile and juvenile neuronal ceroid lipofuscinosis.

PMID- 8739948
TI  - Prenatal diagnosis of systemic disorders of the respiratory chain in cultured
      chorionic villus fibroblasts by study of ATP-synthesis in digitonin-permeabilized
      cells.

PMID- 8739949
TI  - Regulation of the mitochondrial ATP-synthase in skeletal muscle from children--a
      new diagnostic tool.

PMID- 8739950
TI  - Mitochondrial damage: an important feature in a number of inborn errors of
      metabolism?

PMID- 8739951
TI  - Respiratory-chain and pyruvate metabolism defects: Italian collaborative survey
      on 72 patients.

PMID- 8739952
TI  - Benign mitochondrial encephalomyopathy in a patient with complex I deficiency.

PMID- 8739953
TI  - Progressive generalized brain atrophy and infantile spasms associated with
      cytochrome c oxidase deficiency.

PMID- 8739955
TI  - Inhibitory effect of 3-hydroxyacyl-CoAs and other long-chain fatty acid beta
      oxidation intermediates on mitochondrial oxidative phosphorylation.

PMID- 8739954
TI  - X-linked cardioskeletal myopathy and neutropenia (Barth syndrome): respiratory
      chain abnormalities in cultured fibroblasts.

PMID- 8739956
TI  - Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a new method to identify
      the G1528C mutation in genomic DNA showing its high frequency (approximately 90%)
      and identification of a new mutation (T2198C).

PMID- 8739957
TI  - The mutational spectrum in very long-chain acyl-CoA dehydrogenase deficiency.

PMID- 8739958
TI  - Mitochondrial very long-chain acyl-CoA dehydrogenase deficiency with a mild
      clinical course.

PMID- 8739959
TI  - Organic acid profiles resembling a beta-oxidation defect in two patients with
      coeliac disease.

PMID- 8739960
TI  - Retrospective diagnosis of carnitine-acylcarnitine translocase deficiency by
      acylcarnitine analysis in the proband Guthrie card and enzymatic studies in the
      parents.

PMID- 8739961
TI  - Impaired peroxisomal fatty acid oxidation in human skin fibroblasts with a
      mitochondrial acylcarnitine/carnitine translocase deficiency.

PMID- 8739963
TI  - Cholesterol biosynthesis in Zellweger syndrome: normal activity of mevalonate
      kinase, mevalonate-5'-pyrophosphate decarboxylase and IPP-isomerase in patients'
      fibroblasts but deficient mevalonate kinase activity in liver.

PMID- 8739962
TI  - Glycerol trioleate/glycerol trierucate therapy in X-linked adrenoleukodystrophy:
      saturated and unsaturated fatty acids in blood cells. Implications for the follow
      up.

PMID- 8739964
TI  - Clinical and molecular evaluation of Italian patients affected by Pelizaeus
      Merzbacher disease.

PMID- 8739965
TI  - Urinary lactate excretion in type 1 glycogenosis--a marker of metabolic control
      or renal tubular dysfunction?

PMID- 8739966
TI  - Verification of diagnosis in a 17-year-old boy with clinical glycogen storage
      disease type Ia by mutation screening.

PMID- 8739967
TI  - Increased plasma biotinidase activity in patients with glycogen storage disease
      type Ia: effect of biotin supplementation.

PMID- 8739968
TI  - Pulmonary hypertension in glycogen storage disease type I.

PMID- 8739969
TI  - Frequency distribution of the Q188R mutation in the Irish galactosaemic
      population.

PMID- 8739970
TI  - Therapeutic use of carbamylglutamate in the case of carbamoyl-phosphate
      synthetase deficiency.

PMID- 8739971
TI  - 3-Phosphoglycerate dehydrogenase deficiency and 3-phosphoserine phosphatase
      deficiency: inborn errors of serine biosynthesis.

PMID- 8739972
TI  - Molecular basis of non-PKU hyperphenylalaninaemia in Spain: prevalence of A403V,
      a mutation with high residual activity.

PMID- 8739973
TI  - Monitoring treatment in tetrahydrobiopterin deficiency by serum prolactin.

PMID- 8739974
TI  - Treatment of two children with hereditary tyrosinaemia type I and long-standing
      renal disease with a 4-hydroxyphenylpyruvate dioxygenase inhibitor (NTBC).

PMID- 8739976
TI  - Phenotype characterization and prevalence of rBAT M467T mutation in Italian
      cystinuric patients.

PMID- 8739975
TI  - Cultured human keratinocytes as a peripheral source of mRNA for tyrosine
      hydroxylase and aromatic L-amino acid decarboxylase.

PMID- 8739978
TI  - Congenital cataract and familial brachydactyly in carbohydrate-deficient
      glycoprotein syndrome.

PMID- 8739977
TI  - Carbohydrate-deficient glycoprotein syndrome type I: determination of the
      oligosaccharide structure of newly synthesized glycoproteins by analysis of
      calnexin binding.

PMID- 8739979
TI  - Carbohydrate-deficient transferrin values in neonatal and umbilical cord blood.

PMID- 8739980
TI  - Prenatal hypertrophic cardiomyopathy and pericardial effusion in carbohydrate
      deficient glycoprotein syndrome.

PMID- 8739981
TI  - Improved selectivity of urinary oligosaccharide screening using two one
      dimensional TLC systems.

PMID- 8739982
TI  - Diagnostic screening for mucopolysaccharidoses types I-VII by fluorophore
      labelled carbohydrate PAGE.

PMID- 8739983
TI  - A call for logic in the classification of adnexal neoplasms.

PMID- 8739984
TI  - Eosinophilic histiocytosis. Histopathology and immunohistochemistry.
AB  - We review the clinical features, histopathology, and immunohistochemistry in
      three cases of eosinophilic histiocytosis, comparing lymphomatoid papulosis and
      eosinophilic histiocytosis. Each of the patients presented with self-healing
      recurrent papules and ulcerative nodules that were associated with pruritus.
      Disease duration was 5 months to 9 years. Histologically, the lesions
      demonstrated spongiosis and lymphocytic exocytosis, epidermal hyperplasia,
      papillary dermal edema, and a superficial and deep mixed perivascular
      inflammatory infiltrate. The infiltrate showed numerous eosinophils, histiocytoid
      cells, lymphocytes, and large mononuclear cells with atypical hyperchromatic
      nuclei. Most of the lymphocytes and large mononuclear cells with atypical nuclei
      marked with UCHL-1 (T-cell marker). The histiocytoid cells marked with S-100 and
      were dendritic both in the epidermis and the dermis. Eosinophilic histiocytosis
      appears to differ from classic lymphomatoid papulosis. It presents with recurrent
      papules and nodules associated with marked pruritus. Eosinophilic histiocytosis
      uniformly has more eosinophils and does not have the Reed-Sternberg cells often
      observed in lymphomatoid papulosis type A. Eosinophilic histiocytosis does not
      have cells that mark with Ki-1 and shows numerous S-100-positive histiocytoid
      cells that are most likely Langerhans cells, unlike lymphomatoid papulosis.
      However, eosinophilic histiocytosis may be an unusual Ki-1-negative variant of
      lymphomatoid papulosis with histopathologic changes not typical of type A or type
      B. In addition, eosinophilic histiocytosis lacks multinucleated histiocytes and
      the atypical histiocyte with a reniform nucleus, findings that are characteristic
      of histiocytosis X. Further studies are needed to define the pathophysiology and
      prognosis of this apparently distinct entity more accurately.

PMID- 8739985
TI  - Gross cystic disease fluid protein-15 reactivity in extramammary Paget's disease
      with and without associated internal malignancy.
AB  - Extramammary Paget's disease (EMP) is a rare eczematoid disorder occurring mainly
      in apocrine-gland-bearing regions. Its histogenesis is controversial. Several
      investigators have proposed that EMP is a heterologous entity, with some cases
      representing a de novo adenocarcinoma in situ arising in the epidermis and others
      being epidermotropic metastases or a direct extension of an associated internal
      malignancy. We have studied 26 cases of EMP with and without associated internal
      malignancy for their reactivity with a monoclonal antibody directed at gross
      cystic disease fluid protein-15 (GCDFP-15). The diagnosis of EMP has been
      previously established for all cases using histochemical and immunohistochemical
      stains. Six of our 26 cases had a concomitant underlying carcinoma (one
      transitional cell carcinoma of the bladder, four adenocarcinomas of the rectum,
      one adenosquamous carcinoma. Only one of these six cases showed reactivity with
      GCDFP-15. In contrast, 16 of 20 cases of EMP without associated internal
      malignancy were strongly reactive with GCDFP-15 (> 5% of tumor cells). Variable
      GCDFP-15 reactivity in cases of EMP with and without associated internal
      malignancy supports the concept that EMP is a heterologous disorder. Positive
      GCDFP-15 in a patient with EMP may indicate a low probability of associated
      internal malignancy and may provide valuable clinical information.

PMID- 8739987
TI  - A new look at nevus-associated melanomas.
AB  - The frequency with which malignant melanomas arise in association with
      preexisting melanocytic nevi has been studied extensively. We opted to evaluate
      new aspects of this association. In particular, we addressed the relative
      proportions of acquired versus congenital nevi involved and categorized the
      acquired nevi according to morphological type. Approximately 23% of the melanomas
      (29 of 124) in this group arose in association with preexisting nevi of which 55%
      (n = 16) were acquired and 28% (n = 8) were congenital (small). In 17% (n = 5) a
      distinction could not confidently be made. Of the acquired nevi, the vast
      majority were of Clark's type. It is clear that a relatively small proportion of
      melanomas as a whole are associated with preexisting nevi, and this number should
      be kept in perspective in devising strategies for early detection and prevention.
      The involvement of Clark's nevi in this regard is known, but to date the role of
      small congenital nevi has been underrecognized.

PMID- 8739986
TI  - Benign cutaneous adnexal tumors with combined folliculosebaceous, apocrine, and
      eccrine differentiation. Clinicopathologic and immunohistochemical study of eight
      cases.
AB  - Benign cutaneous adnexal tumors displaying divergent differentiation are rare,
      with very few well-documented cases reported in the literature. We describe eight
      cases of benign adnexal tumors showing a variable combination of eccrine,
      apocrine, and folliculosebaceous differentiation. Clinically, all tumors
      presented as solitary, slowly enlarging dermal or subcutaneous nodules located in
      the head and neck and the extremities. Histologically, they were characterized by
      well-circumscribed, unencapsulated nodules composed of a lobular proliferation of
      epithelial cells displaying a spectrum of trichogenic, sebaceous, apocrine, and
      eccrine differentiation. The histological spectrum included lobules and
      trabeculae of basaloid cells with glandular and ductal elements, well-formed
      folliculosebaceous units, primitive follicles, and foci of tricholemmal
      keratinization. Immunohistochemical evaluation in four cases showed similar
      cytokeratin, carcinoembryonic antigen, and epithelial membrane antigen staining
      profiles as those reported for sweat gland adenomas; in addition, focal S-100
      protein positivity and GCDFP-15 positivity could also be demonstrated, suggesting
      eccrine-apocrine differentiation. The tumors were most frequently confused
      histologically with other adnexal neoplasms, including sebaceoma, sebaceous
      adenoma, basal cell carcinoma, chondroid syringoma, and trichoepithelioma. The
      present series highlights the capability.

PMID- 8739988
TI  - Multivariate DNA cytometry discriminates between Spitz nevi and malignant
      melanomas because large polymorphic nuclei in Spitz nevi are not aneuploid.
AB  - To elucidate the reasons for the malignant histologic appearance of melanocytic
      nuclei within benign Spitz nevi (SN), we evaluated nuclear DNA distribution and
      nuclear size using a computerized image analysis system. In each case of 28 SN
      and 34 malignant melanomas (MM), about 100 randomly sampled nuclei were analyzed,
      prepared as monolayers from paraffin-embedded tissues. Large nuclei in MM
      (nuclear area > mean nuclear area of normal melanocytes + 4 delta) were
      significantly more likely to be aneuploid (DNA content > or = 5c) than large
      nuclei in SN chi2 test, p < 0.0001). Only two of 990 large SN nuclei exhibited
      DNA values higher than 5c, whereas 236 of 2,024 large MM nuclei were aneuploid or
      polyploid. Accordingly, in multivariate analysis, five features of DNA
      distribution proved to be most important for objective discrimination between MM
      and SN: 2c deviation index, 5c exceeding rate, standard deviation of the nuclear
      DNA content, and both the 85th and the 95th percentiles of DNA distributions. On
      the basis of these features, we could define a linear discriminant function that
      allowed a correct diagnosis in 94% of the cases. Our data demonstrate that
      diagnostically misleading large nuclei in SN are euploid, in contrast to MM. It
      is thus possible to discriminate SN and MM with high accuracy using DNA
      cytometry. Because paraffin-embedded tissue can be used, this technique could be
      a valuable complement to routine histology in equivocal cases.

PMID- 8739989
TI  - Lipomembranous (membranocystic) fat necrosis. Clinicopathologic correlation of 38
      cases.
AB  - Clinicopathologic correlation of cutaneous biopsy specimens demonstrating typical
      lipomembranous fat necrosis was performed. Material from 732 biopsies of various
      subcutaneous inflammatory disorders seen at our institution in the past 5 years
      was screened for typical lipomembranous (membranocystic) changes in the
      panniculus, and 39 specimens from 38 patients with these changes were identified.
      The most common clinical context in which this condition was observed was in
      chronic sclerotic plaques of the lower legs associated with venous insufficiency
      (37% of the total cases). All patients were women, and the majority were obese.
      Typical lipomembranous fat necrosis was also observed in eight cases (21%) of
      erythema nodosum, three (8%) of morphea or subcutaneous morphea (or both), two
      (5%) of lupus panniculitis, two (5%) of necrobiosis lipoidica, and in single
      cases of polyarteritis nodosa, necrotizing vasculitis, and erysipelas. Six cases
      (16%) had no definite underlying disease. The mean age of all patients was 57
      years (range 32-86 years), and 34 patients (89%) were women. Of the five major
      categories identified, lipomembranes lining macrocysts and microcysts were most
      prominent in the venous insufficiency- and morphea-related cases and were much
      less prominent in erythema nodosum, lupus panniculitis, and necrobiosis
      lipoidica, which generally showed histopathologic findings typical of these
      disorders. In addition to lining the macrocystic and microcystic cavities formed
      in the fat lobules, lipomembranes were prominent in areas of septal fibrosis in
      all cases associated with morphea and necrobiosis lipoidica and in 35% and 25% of
      venous insufficiency- and erythema nodosum-related cases, respectively. In lupus
      panniculitis, lipomembranes were most prominent in areas of hyaline necrosis. We
      conclude that lipomembranous fat necrosis is most likely a nonspecific form of
      ischemic fat degeneration that may be induced by various clinical entities. This
      change is most often seen in venous insufficiency-associated chronic sclerotic
      plaques typically observed in middle-aged obese women, and we propose the term
      stasis-associated lipomembranous panniculitis (SALP) to describe this most common
      form of lipomembranous fat necrosis.

PMID- 8739990
TI  - Epidermolytic hyperkeratosis in nevi. A possible marker for atypia.
AB  - Epidermolytic hyperkeratosis (EH) has been described as a reaction pattern in a
      variety of solitary skin lesions. We have noted that EH seems to occur more
      frequently in association with atypical than with typical acquired nevi. To
      support or refute this observation, the prevalence of EH in 250 cases of atypical
      compound nevi and in 250 cases of typical compound nevi was determined. EH was
      identified in 10 cases of atypical compound nevi and in two cases of typical
      compound nevi, which is a statistically significant difference with p value <
      0.02. Since EH occurred in only 4% of atypical nevi examined, it should not be
      considered a diagnostic criterion. However, the identification of EH in otherwise
      histologically typical nevi should prompt the pathologist to make sure the lesion
      has been adequately sampled.

PMID- 8739991
TI  - Rapid and unbiased estimation of the volume of cutaneous malignant melanoma using
      Cavalieri's principle.
AB  - The Cavalieri volume estimator has been employed to determine the macroscopic
      tumor volume of 34 cutaneous malignant melanomas. With this rapid and unbiased
      method using histological specimens from slabs of known thickness, tumor volumes
      between 3.9 mm3 and 841.5 mm3 were found. The coefficient of error (CE) for tumor
      volumes ranged between 0.028 and 0.141, with a combined group CE of 0.043. There
      was a remarkably good correlation between tumor volume and maximal vertical tumor
      thickness estimated according to Breslow, with a correlation coefficient of r =
      0.86 for all tumors, and of r = 0.82, if the one extremely big tumor is omitted.
      Both inter- and intraobserver variability was very low, with only approximately 1
      2% difference. Thus, the method described allows for the reproducible, rapid, and
      unbiased estimation of tumor volume independent of the shape of the tumor.

PMID- 8739992
TI  - Overexpression of amphiregulin, a major autocrine growth factor for cultured
      human keratinocytes, in hyperproliferative skin diseases.
AB  - Previous studies have indicated that amphiregulin is a major autocrine growth
      factor for cultured human keratinocytes. Its overexpression could therefore be
      important in hyperproliferative skin diseases. The purpose of this preliminary
      study was to determine if there is upregulation of amphiregulin protein in those
      disorders. A variety of lesions was surveyed for qualitative alterations in its
      immunostaining with an anti-amphiregulin monoclonal antibody. Amphiregulin was
      barely detectable in the epidermis of normal controls, although there was random
      nuclear staining of keratinocytes, and the epidermal appendages, especially
      sebaceous glands, were usually reactive. In contrast, psoriatic lesions exhibited
      prominent cytoplasmic staining of basal and spinous keratinocytes. Somewhat
      increased reactivity was also evident in actinic keratoses, in nests of squamous
      carcinoma cells, and in verrucae. Adnexal tumors were often strongly stained.
      Whereas basal cell carcinomas were nonreactive, staining was present in adjacent
      epidermis. Similarly, the melanocytes of nevi and melanoma were nonreactive but
      there was increased staining in contiguous keratinocytes. The pattern of
      amphiregulin immunostaining suggests a role for the protein in the aberrant
      keratinocyte growth of hyperproliferative disorders.

PMID- 8739993
TI  - Papulonecrotic tuberculid in children. A report of eight patients.
AB  - Papulonecrotic tuberculid (PNT), a form of cutaneous tuberculosis (TB), is
      uncommon in children. We identified eight children (six girls and two boys) with
      PNT. Their ages ranged from 19 to 139 months (median 47.5 months, mean:64.75
      months). Skin lesions had been present for 2-24 weeks (median: 4 weeks) before
      diagnosis. All patients displayed scattered papulo- and/or pustulonecrotic
      lesions on the limbs, and the ears were involved in six patients. Lesions healed
      with varioliform scars. Associated pulmonary TB was present in seven patients.
      Additional clinical findings included fever (n = 4), hepatomegaly (n = 4),
      lymphadenopathy (n = 3), phlyctenular conjunctivitis (n = 3), and splenomegaly (n
      = 2). Histology of eight biopsies showed ulceration (n = 6), dermal necrosis (n =
      6) (follicle-centered in two), granulomatous inflammation (n = 6) (palisading
      granuloma-like in three), superficial and deep infiltrate of lymphocytes (n = 7),
      erythrocyte extravasation (n = 7), and subepidermal edema (n = 3). Vasculitis was
      not a feature. A Ziehl-Neelsen stain was negative in all. Glycosaminoglycans were
      not increased. Immunohistochemistry found a predominance of T lymphocytes,
      macrophages, a few antigen-presenting cells, and no B lymphocytes, consistent
      with a type IV hypersensitivity reaction. Polymerase chain reaction (PCR)
      performed on deparaffinized tissue identified M. tuberculosis DNA in one biopsy.
      All patients received combination anti-TB treatment for 6 months. Six patients
      were compliant and were followed up for 6-30 months. Skin lesions and pulmonary
      TB healed in all. PNT in children resembles the adult form, but phlyctenular
      conjunctivitis and associated TB are more common, scrofuloderma and concomitant
      erythema induratum of Bazin are unusual, and vasculitis is not found. In cases
      where M. tuberculosis DNA can be confirmed with PCR, papulonecrotic TB is perhaps
      the more appropriate nomenclature.

PMID- 8739994
TI  - Cutaneous lymphadenoma. A peculiar variant of nodular trichoblastoma.
AB  - Cutaneous lymphadenoma is an uncommon benign epithelial neoplasm with a prominent
      lymphocytic infiltrate. Both a pilosebaceous and an eccrine origin have been
      suggested. We herein document three cases of cutaneous lymphadenoma. Our findings
      support the hypothesis that cutaneous lymphadenoma is a benign tumor with
      follicular differentiation representing a peculiar form of nodular trichoblastoma
      with adamantinoid features and a significant inflammatory cell infiltrate.

PMID- 8739995
TI  - Nodular trichoblastoma with adamantinoid features.
AB  - We report a cutaneous tumor characterized by follicular differentiation and
      adamantinoid features that we consider to be part of the histopathologic spectrum
      of trichoblastoma. Previously, similar lesions have been reported in the medical
      literature as cutaneous lymphadenoma or lymphoepithelial tumor of the skin.

PMID- 8739996
TI  - Fatal hyalohyphomycosis following Fusarium onychomycosis in an immunocompromised
      patient.
AB  - A 35-year-old man with B lymphoblastic lymphoma was treated with bone marrow
      transplant and aggressive chemotherapy. He developed a Fusarium infection of the
      great toenail. Septicemic dissemination of a Fusarium sp. occurred 9 months later
      during a lymphoma relapse. The clinical course of the hyalohyphomycosis was then
      rapidly fatal despite institution of amphotericin B therapy.

PMID- 8739997
TI  - Granulomatous slack skin. Report of a case and review of the literature.
AB  - We describe a patient with granulomatous slack skin (GSS) who has been followed
      for 15 years and present clinical, histological, immunohistochemical,
      ultrastructural, cytogenetic, and molecular findings. The clinical and
      pathological aspects of the 20 cases of GSS reported in the recent literature are
      reviewed and compared with those of the present case.

PMID- 8739999
TI  - Atrophoderma elastolytica discreta.
AB  - Atrophoderma elastolytica discreta is the clinicopathologic name for a unique
      entity herein first described in a patient with cutaneous lesions simulating
      atrophoderma of Pasini and Pierini but coupled with histopathologic changes of
      anetoderma. The clinical and histological findings seen here have not been
      previously seen in the many variants of anetoderma, and, as such, they are sui
      generis evidence of a new entity in clinical dermatology.

PMID- 8739998
TI  - Eccrine syringofibroadenoma (Mascaro). An ultrastructural and immunohistochemical
      study.
AB  - Eccrine syringofibroadenoma is a rare benign skin tumor, which usually develops
      on the extremities of elderly persons. We performed immunohistochemical and
      ultrastructural studies of a typical case of eccrine syringofibroadenoma that
      developed on the left heel of a 58-year-old man. The tumor consisted of
      anastomosing thin epithelial strands connected to the epidermis. There were many
      ductal or cystic structures, and their luminal cells were strongly positive to
      antibodies against carcinoembryonic antigen and epithelial membrane antigen.
      Filagrin and involucrin immunoreactivities were also detected in some cells
      surrounding the ducts. Keratins K1 and K10, co-expressed in the peripheral cells
      of normal acrosyringia, were colocalized in small cell clusters.
      Ultrastructurally, intracellular duct formation characteristic of developing
      acrosyringia was observed. Tumor cells containing globular keratohyaline granules
      with various electron densities were seen around some ductal structures. In these
      areas, keratinization took place without lamellar granule formation or prominent
      cornified cell envelope assembly. These results suggest acrosyringial
      differentiation of this tumor.

PMID- 8740000
TI  - Giving credit where it is due.

PMID- 8740001
TI  - EMH in pilomatricomas.

PMID- 8740002
TI  - The Rh antigen D: partial D antigens and associated low incidence antigens.
AB  - The expression of the Rh antigen D varies quantitatively and qualitatively
      (partial D); published information and 15 years' work studying D variants are
      discussed in this review. D epitopes correspond to the reaction patterns of
      monoclonal anti-D with partial D antigens. Partial D antigens can be reported in
      terms of their D epitopes but the epitope profile of cells with a quantitative
      variant of D (weak D) is difficult to determine reliably by haemagglutination
      tests. Nine partial D antigens, categories II-VII, DFR and two not previously
      reported, are identified by their epitope profiles and by association with low
      incidence antigens. Monoclonal anti-D recognize 16 D epitopes and more epitopes
      are anticipated. The specificities of polyclonal anti-D made by people with
      partial D antigens are considered in terms of possible D epitope specificities:
      recognized epitope specificities, or combination thereof, were not able to
      account for all observed reaction patterns of anti-D made by immunized
      individuals with partial D phenotypes. An attempt is made to understand partial D
      antigens and their associated low incidence antigens in terms of the molecular
      genetic information available.

PMID- 8740003
TI  - Analysis for recovery and loss of mononuclear cells and colony-forming units
      granulocyte-macrophage during ex vivo processing of autologous bone marrow.
AB  - During ex vivo processing of autologous bone marrow (BM) substantial loss of stem
      and progenitor cells should be avoided to achieve rapid and sustained
      hematopoietic reconstitution after high-dose radio-/chemotherapy. We processed 25
      autologous BM grafts with the Fresenius AS104 cell separator for cryopreservation
      and we determined recoveries for mononuclear cells (MNC) and colonyforming units
      granulocyte-macrophage (CFU-GM) in the BM concentrates. To identify cell loss in
      BM fractions not cryopreserved, we investigated the MNC and CFU-GM content of BM
      fat and BM blood. MNC and CFU-GM recovery yielded a mean ( +/- SEM) of 42 +/- 12
      and 54 +/- 20% in the BM concentrate. BM fat showed a mean loss of 7 +/- 5% for
      MNC and 4 +/- 3% for CFU-GM, BM blood 30 +/- 12% for MNC and 13 +/- 13% for CFU
      GM, respectively. CFU-GM recovery was significantly higher in the BM concentrate
      of patients with hematologic malignancy (HM) compared with patients suffering
      from germ cell cancer (GCC): 66 +/- 21 vs. 43 +/- 12% (p < 0.02). Seventeen
      patients (7 GCC, 10 HM) underwent high-dose chemotherapy or radio-/chemotherapy
      and were autografted with 0.8 +/- 0.2 x 10(8) MNC/kg and 3.7 +/- 2.0 x 10(4) CFU
      GM/kg. All patients achieved engraftment with neutrophils > 0.5 x 10(9)/l at a
      mean of 14 +/- 6 days. We conclude that: (1) ex vivo processing of autologous BM
      with a mean of recovery of 42% for MNC and 54% for CFU-GM in the BM concentrate
      can result in a cell population capable of sustained hematopoietic
      reconstitution, (2) CFU-GM recovery is significantly higher in patients with HM
      than in patients with GCC and (3) 37% MNC and 17% CFU-GM represent in fact cell
      losses recovered from BM fractions not cryopreserved (BM fat, BM blood).
      Furthermore, it is likely that MNC and CFU-GM not recovered from BM concentrate,
      BM fat and BM blood are cell losses related to the cell separator.

PMID- 8740004
TI  - HCV-Infection in blood donors: association between anti-HCV core IgM antibodies
      and serum HCV RNA.
AB  - Among 47 blood donors tested positive with HCV EIA 2.0 Abbott, 27 (57.4%) also
      reacted with four ?third-generation' EIAs. The presence of anti-HCV antibodies
      was confirmed with 3 different immunoblot assays in 16 of 27 sera (34.0%) while
      10 samples (21.3%) had indeterminate profile with antibodies usually directed
      against structural core antigen. Anti-HCV core IgM response was found in 12 of 47
      sera (25.5%) and HCV viremia detected by the polymerase chain reaction (PCR)
      procedure was observed in 15 samples (31.9%). A comparative study of the
      different markers confirmed a good correlation between a strong antibody response
      in EIAs and immunoblot assays and the presence of HCV RNA in the serum; only 2
      immunoblot indeterminate samples were PCR positive. An association was observed
      between IgM antibodies against "core' epitopes and HCV RNA carriage: all IgM
      positive sera were found positive by PCR. However, the direct detection of viral
      genome remains the best method for identifying HCV carriers in the blood donor
      population.

PMID- 8740005
TI  - False negative anti-HIV-1/HIV-2 ELISAs in acute HIV-2 infection.
AB  - Since HIV-2 was isolated in 1986, only 1 case of acute HIV-2 infection has been
      reported. We have identified another patient with primary HIV-2 infection. Follow
      up samples were requested from the patient due to discrepant results. The HIV-2
      infection was confirmed with HIV-2-specific proviral DNA amplification by PCR.
      The HIV-2 seroconversion panel obtained was used to evaluate the sensitivity of
      both combined and specific ELISAs currently in use in Europe, and to investigate
      the Western-blot patterns on both HIV-1-and HIV-2-specific Western blots. The
      window period was determined to be less than 37 days with the most sensitive
      assays. A remarkable difference in sensitivity to HIV-2 antibodies in acute HIV-2
      infection was found in combined HIV-1/HIV-2 ELISAs. Three out of the 4 combined
      sandwich ELISAs appeared to be less sensitive than the indirect ELISAs in HIV-2
      seroconversion, leading to a prolonged window period. One HIV-2-specific ELISA
      was also negative on the first sample, but positive on the second sample. In the
      HIV-2 Western blot, early reaction with HIV-2-specific env and gag proteins was
      seen, whereas the HIV-1 Western blot on the first sample revealed gag (p24, p55)
      reactivity only.

PMID- 8740006
TI  - Collaborative study to assess the suitability of an HCV RNA reference sample for
      detection of an HCV RNA in plasma pools by PCR.
AB  - A collaborative study was undertaken to examine the sensitivity and
      reproducibility of hepatitis C virus (HCV) RNA PCR assays of plasma pools in
      order to establish a reference sample for HCV PCR testing of plasma pools.
      Samples consisting of an HCV-RNA-positive donation diluted tenfold in an HCV-RNA
      negative cryosupernatant were sent to 16 participating laboratories (including
      blood product manufacturers and control authorities). The results of the in-house
      assays indicate that a 10(-4) dilution of the positive donation in the
      cryosupernatant could be used as the reference sample as this was the highest
      dilution of the positive donation that was detected in all assays. In contrast,
      the results obtained with a commercially available assay, designed for use with
      single-donation plasma or serum (Roche Amplicor TM HCV test), were not so clear
      cut and the assay appeared to be ten-fold less sensitive than the in-house
      assays.

PMID- 8740007
TI  - A new microplate red blood cell monolayer technique for screening and identifying
      red blood cell antibodies.
AB  - A new method has been developed to immobilize red blood cells in wells of
      microplates using a cell fixation buffer. This method has been employed for
      detecting and identifying red blood cell antibodies with greater sensitivity than
      haemagglutination antiglobulin tests, without loss of specificity. This method
      decreases the amount of test erythrocytes and anti-human globulin reagents
      employed per test, consequently lowering the cost.

PMID- 8740008
TI  - Inhibition of the monocyte chemiluminescent response to anti-D-sensitized red
      cells by Fc gamma RI-blocking antibodies which ameliorate the severity of
      haemolytic disease of the newborn.
AB  - Luminol-enhanced chemiluminescence (CL) may be used to measure the metabolic
      response of human monocytes to red cells sensitized by anti-D. The functional
      activity of maternal anti-D when measured in this way correlates with the
      severity of haemolytic disease of the newborn (HDN) in D-positive fetuses.
      Occasionally, however, women with levels of functionally active anti-D predictive
      of moderate to severe HDN may deliver D-positive babies with unexpectedly mild
      disease. In the current study we have shown that serum from 12 of 15 such women
      contained monocyte-binding IgG antibodies which blocked Fc gamma RI and inhibited
      the CL response of monocytes to red cells sensitized with monoclonal anti-D. In
      contrast, Fc gamma RI-blocking antibodies were found in the serum from only 4 of
      11 women who were matched for anti-D activity but who delivered babies with
      severe HDN (p < 0.05). Antibodies responsible for inhibition of CL responses were
      predominantly against HLA class I antigens. The CL response of monocytes to
      sensitized red cells was at least as sensitive to inhibition by Fc gamma RI
      blocking antibodies as were phagocytic and lytic responses. Our data suggest that
      inhibition of the CL test is an objective, sensitive and relatively simple
      technique for detecting and investigating Fc gamma RI-blocking antibodies which
      may ameliorate the severity of HDN.

PMID- 8740009
TI  - DNA-based rhesus typing: simultaneous determination of RHC and RHD status using
      the polymerase chain reaction.
AB  - We describe a PCR-based method of performing RHD and C/c typing in a single
      reaction. The method is based on an earlier observation of a polymorphism in
      intron 2 of both genes which, in addition to detecting the RHD deletion
      responsible for most known D-negative phenotypes, is also associated with C/c
      serological type. Using this assay, we typed 105 unrelated individuals from at
      least four different population groups and compared the results to those obtained
      using conventional serological testing of red cells. An absolute correlation,
      with no exceptions, was seen. We also showed that the method has potential in the
      antenatal determination of RH type, as it was possible to type fetal trophoblasts
      recovered from the endocervical canal at 9 weeks pregnancy.

PMID- 8740010
TI  - The D antigen characteristic of RoHar is a partial D antigen.
AB  - The results of testing RoHarr cells with panels of monoclonal anti-D suggest that
      the D antigen (referred to as DHar) encoded by the haplotype (D)c(e) Rh33 is a
      partial D antigen. IgM monoclonal anti-D are more efficient than IgG monoclonal
      anti-D in detecting DHar.DHar expresses some but not all of both epD5 and epD6/7
      and appears to lack epD1-epD4, epD8 and epD9.

PMID- 8740011
TI  - Selection of monoclonal antibodies for the identification of D variants: ability
      to detect weak D and to split epD2, epD5 and epD6/7.
AB  - Red cells from known D variant donors were tested with 41 monoclonal anti-D
      reagents, 26 IgG and 15 IgM, with the view to selecting a panel to aid the
      identification of unusual D types. These antibodies gave reaction patterns which
      allowed the identification of most of the known D category cells, recognizing
      epD2, epD5, epD6/7, epD8 and epD9, but were unable to distinguish category III
      from normal D-positive cells. Reactivity with HMi, HMii, DFR, DBT and RoHar cells
      split epD2, epD5 and epD6/7 into two, three and eight groups, respectively. A
      panel comprising 15 monoclonal anti-D, 11 IgG and four IgM, was selected as
      representative of the antibodies tested. Reactivity of monoclonal anti-D was
      dependent on antibody concentration and antibody avidity. An antibody
      concentration of at least 12 micrograms/ml was required for optimum reactivity of
      the two monoclonal antibodies tested. A simple calculation of division of the
      titre by the antibody concentration provided a relatively simple means of
      establishing the reactivity performance of the antibody and correlated well with
      ability to detect weak D (Du) cells. A characteristic variable reduction in
      reaction strength with all the IgG anti-D was observed with weak D cells. The IgM
      antibodies, except the high avidity RUM-1, T3D2T6, D9A4 and BS226, performed
      poorly in detecting weak D. The majority of the IgM antibodies tested reacted
      with RoHarr cells, while only one IgG antibody was positive.

PMID- 8740012
TI  - Analysis of autologous blood donor motivation.

PMID- 8740014
TI  - Seroprevalence of HTLV-I/II in different groups at risk in northeast Mexico.

PMID- 8740013
TI  - Circulating hepatitis C virus genotypes in Spain. The Hepatitis/HIV Spanish Study
      Group.

PMID- 8740015
TI  - Royal College of Physicians, Edinburgh: final consensus statement. Consensus
      Conference on Autologous Transfusion, 4-6 October, 1995.

PMID- 8740016
TI  - Danish recommendations for the transfusion of leukocyte-depleted blood
      components. The Danish Society of Clinical Immunology.

PMID- 8740017
TI  - Interstitial cystitis: involvement of the intestine.
AB  - Two patients with intractable interstitial cystitis are presented. Both have had
      substitution enterocystoplasty and in both, unabated symptoms have resulted in
      ileal loop diversion. In both patients the excised neobladder had shown extensive
      changes of interstitial cystitis involving all layers, including the muscle
      layers of the explanted intestine. Also in one of these patients, symptoms
      suggestive of interstitial cystitis persisted and biopsies taken from the ileal
      loop have shown histological changes characteristic of interstitial cystitis. The
      presentation of interstitial cystitis in the intestine is discussed and we
      conclude that interstitial cystitis does manifest in the intestine.

PMID- 8740018
TI  - Postchemotherapy surgery in nonseminomatous testicular tumors.
AB  - Two hundred and twenty patients with metastatic nonseminomatous germ cell
      testicular tumors received primary chemotherapy including cisplatin, vinblastine
      and bleomycin (PVB). Complete response was achieved with chemotherapy alone in
      108 (49.1%) patients. Postchemotherapy surgery of the residual mass was done in
      85 (38.6%) patients with normalized serum tumor markers. Laparotomy was done in
      62 patients, 19 patients underwent thoracic surgery, and 4 patients had both
      postchemotherapy treatments. Thirteen (5.9%) patients had persistently elevated
      serum tumor markers, they died despite salvage second-line chemotherapy. Fourteen
      (6.4%) patients died during primary PVB chemotherapy. The masses removed at
      laparotomy consisted of necrotic and/or fibrotic tissue in 25.8%, mature teratoma
      in 61.3% and viable cancer was detected in 12.9% of cases. In contrast, resected
      pulmonary masses consisted of necrotic and/or fibrotic tissue in 42.1%, mature
      teratoma in 26.3% and viable cancer in 31.6%. The total therapeutic outcome in
      220 patients was as follows: 159 (72.3%) patients are alive and free of disease;
      4 (1.8%) patients live with disease, and 57 (25.9%) died of the disease.

PMID- 8740019
TI  - A heterogeneous pattern of progression in endocrine-treated patients with
      prostate cancer.
AB  - Prostatic carcinoma often shows different behavior in the primary site than in
      the metastases after endocrine treatment. The pattern of disease progression was
      evaluated in prostate cancer patients. Two hundred and sixty consecutive patients
      were observed following the initiation of endocrine treatment (11 patients with
      stage T1 disease, 42 with stage T2 70 with stage T3, 11 with N + M0 and 126 with
      stage M1 disease). Of the 117 patients whose disease progressed, 100 could be
      evaluated in terms of the pattern of disease progression. Twenty-two (64.7%) of
      the 34 patients with stage T1-3N0M0 showed a pattern of local progression. On the
      other hand, 56 (84.8%) of the 66 patients with stage N + or M1 experienced a
      pattern of distant progression. Patients with only distant progression numbered
      36 cases and patients with local progression and distant progression numbered 20
      cases. Most of the distant progressions appeared in bone site. Local progression
      was observed in only 30 (45.5%) patients with stage N + or M1 disease. In
      patients with localized disease (T1-3N0M0), both the interval to disease
      progression and the time to cancer death from the start of disease progression
      were significantly longer than those of patients with stage N + or M1. However,
      once bone metastasis occurred, the disease tended to progress rapidly. There was
      no significant difference between the interval to cancer death after the
      appearance of bone metastasis in patients with initially localized stages (T1
      3N0M0) and the time to cancer death after disease progression in patients with
      metastatic disease (N + or M1). The study shows a heterogenous behavior of the
      prostatic tumor after endocrine treatment. This suggests that metastases and
      primary tumor have different clonal compositions. The study also supports the
      idea that there is a preferential environment for the growth of prostatic
      carcinoma cells in bone sites.

PMID- 8740020
TI  - Rectal perforation after retropubic radical prostatectomy: occurrence and
      management.
AB  - OBJECTIVES: A surgical audit of the management of rectal perforations during
      retropubic radical prostatectomy. Assessment of incidence, risk factors,
      management and outcome. METHODS: All 10 cases (3.6%) sustaining a rectal injury
      of a total series of 270, while undergoing retropubic radical prostatectomy at
      our 2 institutions were reviewed. In all cases, the injury was immediately
      recognized and treated by primary suture, anal dilatation and antibiotics. In 1
      case, a temporary colostomy was performed. RESULTS: Recovery was uneventful in
      all cases, and the postoperative hospitalization was only slightly longer than
      usual in the 9 cases without fecal diversion. No fistulae or wound infections
      occurred, but closure of 1 colostomy was complicated. CONCLUSION: Provided that
      the injury is promptly recognized and properly sutured, a rectal perforation at
      radical prostatectomy is not of great significance and should not deter from an
      adequate preoperative investigation by multiple transrectal core biopsies or
      neoadjuvant hormonal treatment. The use of preoperative bowel preparation,
      routine antibiotic prophylaxis, omental interposition or a proximal colostomy
      does not appear to be necessary in order to achieve immediate safe repair.

PMID- 8740021
TI  - Use of an intraurethral catheter instead of a Foley catheter after laser
      treatment of benign prostatic hyperplasia.
AB  - OBJECTIVE: Our study describes the results obtained in 15 patients in whom an
      intraurethral catheter (IUC) instead of an indwelling catheter was used after
      visual laser ablation of the prostate (VLAP). METHODS: The 15 patients were
      treated by VLAP for benign prostatic hyperplasia. The IUC was inserted through
      the cytoscope sheath immediately after completion of surgery, and left in the
      prostatic urethra for 3 weeks. RESULTS: Twelve of the 15 patients (80%) voided
      through the urethra without need of an indwelling catheter. In the remaining 3
      patients the IUC had to be removed and a Foley catheter inserted. CONCLUSION: Our
      results reveal that the IUC stent may be used as an alternative for an indwelling
      catheter in patients treated by VLAP.

PMID- 8740022
TI  - Stromal nodules in benign prostatic hyperplasia.
AB  - OBJECTIVE: Stromal nodules from benign prostatic hyperplasia (BPH; n = 375 from
      autopsy, n = 100 from biopsy specimens) were investigated with regard to
      cytoskeletal components, topography, vascularization, leukocytic infiltrates, and
      proliferative activity. METHODS: The nature of stromal nodules was studied by
      histopathology and immunohistochemistry, using antibodies against alpha-actin,
      desmin, myosin, vimentin, BMA-120, factor VIII, CD3, CD4, CD20, CD34, CD45RO,
      CD68, PCNA, and MiB1. RESULTS: The findings lead to an extended classification of
      stromal nodules in BPH: immature mesenchymal (IM; 8.8%), fibroblastic (FB; 65.2),
      fibromuscular (FM; 21.6), and smooth muscular (SM; 4.4%). The different types
      occurred in all age decades in a similar distribution (FB > FM > IM > SM).
      Topographical studies (modified zonal subdivision of McNeal) revealed stromal
      nodules predominantly in the transitional zone (n = 286), less in the central
      zone (n = 78), occasionally in the peripheral zone (n = 11), and predominantly in
      the periurethral (n = 287) and less in the intermediate (n = 84) and subcapsular
      (n = 4) regions. The different types of nodules presented a distinct vascular
      pattern. FB, FM, and SM nodules showed significantly increased diffuse
      infiltrates of T lymphocytes-mainly T helper cells (mean 73%)-and an increase of
      B lymphocytes. Proliferative activity in the nodules was not observed. Stromal
      nodules were not observed in normal nonhyperplastic prostates; they only occurred
      in combination with hyperplastic nodular glandular proliferates. CONCLUSIONS: The
      findings are suggestive of a maturational sequence of stromal nodules in BPH and
      of a possible significance of immunocompetent cells in the development of stromal
      nodules and further suggest that both stroma and epithelium of the prostate
      respond with nodular hyperplasia to the stimulus, which causes BPH.

PMID- 8740023
TI  - Morphological and X-ray microanalytical changes in mammalian tissue after
      overhydration with irrigating fluids.
AB  - We compared morphological changes in the heart, brain, liver and kidneys after
      giving 100 ml/kg of 5 irrigating fluids by intravenous infusion to 30 rabbits.
      Glycine 1.5% and 1.0%, both with ethanol 1% as a tracer for absorption, received
      the highest scores for tissue swelling and were sometimes followed by focal
      necrosis and an inflammatory cell reaction in subendocardial areas of the heart.
      Three rabbits died shortly after infusion of glycine 1.5% + ethanol 1%, the
      deaths being preceded by bradycardia and an irregular cardiac rhythm. This
      solution also lowered the intracellular potassium and chlorine content as shown
      by X-ray microanalysis of myocardial cells. Mannitol 3% + ethanol 1% produced the
      most favorable outcome in our evaluation, with the lowest scores for tissue
      swelling, while sorbitol 2% + mannitol 1% and normal saline took intermediate
      positions.

PMID- 8740024
TI  - Evidence of nonadrenergic, noncholinergic contraction in rat urinary bladder by
      1,1-dimethylphenylpiperazinium stimulation in vivo.
AB  - Nonadrenergic, noncholinergic (NANC) contraction has been demonstrated in animal
      urinary bladder. However, the exact nature of the NANC innervation is still
      unclear. 1,1-Dimethylphenylpiperazinium (DMPP), which generates action potentials
      in the cell body of the postganglionic neuron and causes neurotransmitter release
      (both acetylcholine and noradrenaline), was given intravenously (0.1-0.7 mg/kg)
      to 3-month-old female Wistar rats under anesthesia (n = 20). Intravesical
      pressure, heart rate and blood pressure of the rats were monitored on Gould
      polygraph. Monophasic dose-dependent contractile response was observed upon
      administration of DMPP in 12 of 20 rats. After total adrenergic and cholinergic
      blockade with atropine, guanethidine, phentolamine and propranolol, the
      contractile response was reduced, not completely, in the animals. At the dose of
      0.7 mg/kg, the contraction was reduced to about 48% of the original response. The
      study provides in vivo evidence for NANC contraction in the rat urinary bladder,
      moreover, the neurotransmitter is released from the postganglionic neurons.

PMID- 8740025
TI  - Procollagen type I carboxyterminal extension peptide in serum: a reliable marker
      of bone metastatic disease in newly diagnosed prostate cancer?
AB  - OBJECTIVE: This study evaluates the accuracy of type I procollagen, a bone matrix
      glycoprotein, and prostate-specific antigen (PSA) as markers for predicting the
      results of radionuclide bone scan in newly diagnosed, previously untreated
      patients with prostate cancer. METHODS: 74 patients underwent serum PSA and
      procollagen determination using specific antibodies. A staging radionuclide bone
      scan was then performed; patients with positive bone scan were submitted to x
      rays of the suspicious zones. Then, we calculated sensitivity, specificity,
      positive predictive value, negative predictive value and overall accuracy of
      procollagen and PSA in the detection of bone metastases. RESULTS: Procollagen
      alone had 83.3% sensitivity, 96% specificity, 90.9% positive predictive value,
      92.3% negative predictive value and 91.9% overall accuracy. PSA alone had 70.1%
      sensitivity, 86% specificity, 70.8% positive predictive value, 86% negative
      predictive value and 81.1% overall accuracy. CONCLUSIONS: According to our data,
      we no longer perform a staging radionuclide bone scan in patients with PSA < 20
      ng/ml and normal procollagen level, diminishing the number of radionuclide bone
      scans and increasing the overall net savings for the health care system.

PMID- 8740026
TI  - Expression of CD44 splice variants in human transitional cell carcinoma.
AB  - The CD44 cell adhesion molecule is a surface glycoprotein mainly expressed in
      lymphoid tissues. Recently, abnormal variants of CD44 including alternatively
      spliced large molecular variants, have been reported in many neoplastic tissues.
      We studied the variation in the size of CD44 molecules in 25 transitional cell
      carcinomas and 11 normal transitional epithelial tissues, using the reverse
      transcriptase-polymerase chain reaction (RT-PCR) followed by electrophoresis and
      Southern blot hybridization. Whereas 23 of 25 (92.0%) tumor tissues expressed
      CD44 splice variants with large molecular size, only 1 of 11 (9.1%) normal
      tissues expressed the abnormal variants. Urine sediments from 5 of 7 (71.4%)
      patients also was positive for the CD44 splice variants. CD44 splice variants are
      increased markedly in human transitional cell carcinoma. In conclusion, detection
      of CD44 splice variants using the RT-PCR, which is a convenient molecular
      biological technique, may be useful in combination with other diagnostic methods
      such as cytology, flow cytometry, and tumor antigens.

PMID- 8740027
TI  - Consensus meeting on new approaches in the pharmacotherapy of benign prostatic
      hyperplasia (BPH). Proceedings of the meeting held on the 8th and 9th October
      1994 in St. Tropez, France, under the patronage of the International Academy of
      Biomedical and Drug Research.

PMID- 8740028
TI  - Advances in the assessment of clinically localized prostate cancer.
AB  - OBJECTIVE: We review the advances in pathology, biology, and radiology which
      could improve the detection of extracapsular prostate cancer preoperatively.
      METHOD: The experiences of others are compared to ours to give a topical overview
      of advances in the assessment of clinically localized prostate cancer. RESULTS:
      Despite new technologies, such as colour Doppler and endorectal magnetic
      resonance imaging, radiology does not enhance the ability to detect small
      invasion through the prostatic capsule. Biopsy features are one of the new fields
      of investigation. The number of positive sextant biopsies and the analysis of
      periprostatic spaces on biopsies appear to be major prognosis factors. In our
      experience, capsular perforation on biopsy is very powerful with respect to the
      proportion of positive biopsies ( > 66.7%) and serum PSA ( > 25 ng/ml, polyclonal
      assay) to predict biological progression after radical prostatectomy. The utility
      of the proportion of invaded tissue on biopsy is still debated. CONCLUSIONS:
      Despite technical improvements, the staging of clinically confined prostate
      cancer is still a major issue. The best hope comes from the study of biopsy
      features in addition to PSA.

PMID- 8740030
TI  - Organ-sparing treatment for ureteral carcinoma?
AB  - OBJECTIVE: Nephroureterectomy (NUE) with a bladder cuff is the standard therapy
      for ureteral cancer. Based on an analysis of the literature and a retrospective
      study, this concept is questioned. METHODS: Between 1980 and 1991, 40 patients
      with ureteral tumors underwent surgery at the Krankenhaus der Barmherzigen Bruder
      in Munich. Tumoral stages were pTa and pTl in 62% of the patients; 37% showed an
      invasive carcinoma. Radical surgery (NUE with bladder cuff) was performed in 22
      patients and conservative treatment (ureterocystoneostomy or end-to-end
      anastomosis) in 13 patients. RESULTS: The median follow-up was 42 months in the
      conservative group and 59 months in the radical surgery group. A recurrence in
      the conservatively operated patients was observed only in primary invasive tumors
      (4/13), whereas none of the remaining patients had a recurrent tumor. In terms of
      time to progression and tumor-specific survival, there was a good correlation of
      the ureteral carcinoma according to grading and staging. In terms of survival,
      patients with superficial tumors run a similar course whether treated by
      conservative or radical surgery. CONCLUSION: The conservative treatment of
      patients presenting with superficial ureteral lesions seems to be a good
      alternative to radical surgery.

PMID- 8740029
TI  - Prognostic factors of primary transitional cell carcinoma of the upper urinary
      tract.
AB  - OBJECTIVES: We presented and analyzed our results in order to determine the
      relationship between patient survival and tumor grade and/or stage. In addition,
      a retrospective tumor DNA ploidy study was done to evaluate its possible role in
      predicting future tumor recurrence in the bladder. METHODS: A total of 112
      patients with upper urinary tract transitional cell carcinomas (TCCs) were
      recorded at our hospital. Of these, 68 patients without concurrent bladder tumors
      (ages ranged from 36 to 80, mean 62.4 years; male:female = 1:1.2) were treated by
      nephroureterectomy and bladder cuff resection. They were followed up for 14-79
      months (average 38.2 months). Eight (36.4%) of the 22 patients who had stage C or
      D tumors had received adjuvant systemic methotrexate, vinblastine, epirubicin,
      cisplatin chemotherapy after surgery. DNA flow cytometry using paraffin-blocked
      tumor specimens was performed on the tumors of 52 patients. RESULTS: Their
      pathologic stages and grades were 11 at stage 0, 15 at stage A, 20 at stage B, 14
      at stage C, 8 at stage D; 9 of grade I, 41 of grade II, and 18 of grade III.
      Postoperatively, 13 patients (19.1%) subsequently developed bladder tumors with a
      latent period ranging from 2 to 37 months (average 14.9 months). The difference
      of the tumor DNA ploidy distribution pattern among tumors of high versus low
      stages and/or grades is not statistically significant (p > 0.05). Overall, the 5
      year survival rates for patients with low- and high-stage tumors were 100 and
      66.7%, respectively; for patients with grade I-II and III tumors they were 93.6
      and 28.3%, respectively. CONCLUSIONS: Patient survival was mainly related to both
      tumor stages (p = 0.0037) and grades (p = 0.0001), rather than to tumor DNA
      ploidy. For patients with grade II upper urinary tract tumors, tumor DNA ploidy
      seems to provide no additional predictive value on subsequent tumor recurrence in
      the bladder.

PMID- 8740031
TI  - Renal cell carcinoma: histological findings in peritumoral tissue after organ
      preserving surgery.
AB  - OBJECTIVE AND METHOD: This study assessed the involvement of peritumoral renal
      cell carcinoma tissue and evaluated the efficacy of partial resection versus
      enucleation by an anatomopathological investigation into the resection margins in
      28 cases of partial nephrectomy. RESULTS: Histological findings showed no
      peritumoral infiltration in 91.6% of elective partial resections (24 patients)
      and resection margin involvement in 75% of necessary partial resections (4
      patients). CONCLUSION: Although the debate between organ-preserving and radical
      surgery remains open, the conservative approach can undoubtedly be recommended in
      selected patients.

PMID- 8740032
TI  - The case against fine-needle aspiration cytology for small solid kidney tumors.
AB  - Conservative renal cell cancer surgery in elective conditions can be applied if
      the tumor is solitary and well delineated on the CT scan and easily resectable
      within a rim of healthy parenchyma. A number of solid tumors will prove not to be
      malignant on definite pathological examination. The radiological preoperative
      differential diagnosis of a small renal mass is not always obvious. The efficacy
      of fine-needle aspiration cytology in recognizing the pathology of the tumor
      before surgery is limited and major complications have been reported. Moreover,
      it can render a conservative surgical procedure less safe. Thus fineneedle
      aspiration cytology is not recommended if conservative surgery is planned, unless
      renal involvement by metastasis or lymphoma is suspected.

PMID- 8740033
TI  - Laparoscopic versus lumboscopic nephrectomy.
AB  - OBJECTIVES: The aim of this study is to compare the initial experience at two
      different urologic centers of the 20 first laparoscopic nephrectomies performed
      either by transperitoneal laparoscopy (10 cases) in one center or by
      retroperitoneal laparoscopy (lumboscopy, 10 cases) in the other center. METHODS:
      5 males and 15 females with a mean age of 36 years (range 3-74) were operated on
      the right side in 8 cases and on the left side in 12 cases. Nephrectomies were
      indicated in 18 cases for benign renal disease, and in 2 cases for ureteric tumor
      (1 patient in each group). The techniques of these two approaches are described.
      RESULTS: The mean operating time was shorter with lumboscopy (173 min) than with
      laparoscopy (210 min), probably due to the direct approach to the renal
      compartment without intraperitoneal dissection with lumboscopy. There were no
      severe intraoperative or postoperative complications, but one hematoma of the
      renal area in the laparoscopic group. The mean postoperative hospital stay was
      identical following lumboscopy and laparoscopy (4.3 and 4.2 days, respectively).
      CONCLUSION: These two approaches can be used to perform nephrectomy. In this
      initial experience, the results appear to be equivalent in terms of morbidity and
      postoperative hospital stay, but the operating time appears to be shorter with
      lumboscopy. Larger studies comparing respective nephrectomy conversion rates
      would provide other arguments in favor of one or other of these techniques.

PMID- 8740034
TI  - Management of acute hydronephrosis in pregnancy by ureteral stenting.
AB  - Acute hydronephrosis during pregnancy that fails to respond to conservative
      treatment can be managed by ureteral stenting or in special cases by application
      of a percutaneous nephrostomy tube. We report the outcome in 116 pregnant women
      with symptomatic hydronephrosis. In 30 cases ureteric stents were passed under
      local anesthesia. In 2 cases (pyeloureteral stenosis, impacted ureteric stone)
      percutaneous nephrostomy was necessary. Overall each course of pregnancy and
      disease was individually decided. In case of persisting symptoms due to acute
      hydronephrosis, ureteral stenting was preferred, since it is a simple, safe and
      effective method of internal upper urinary tract drainage.

PMID- 8740035
TI  - Renal hemodynamics in patients with obstructive uropathy evaluated by color
      Doppler sonography.
AB  - OBJECTIVES: Prior animal studies have shown through direct pressure measurements
      that there is a definite rise in the renal vascular resistance in obstruction.
      Therefore intrarenal hemodynamic changes can be determined by the vascular
      impedance expressed as pulsatility and resistive indexes (PI and RI) obtained
      from the Doppler waveforms of intrarenal arteries. We investigated whether
      various degrees of obstruction result in different hemodynamic responses
      according to color Doppler sonography. METHODS: 22 kidneys with varied degrees of
      hydronephrosis and 19 normal kidneys were examined. The pulsatility and resistive
      index of Doppler waveforms from interlobar arteries were obtained. The grade of
      hydronephrosis was based upon the width of parenchyma. RESULTS: The mean
      resistive index in the study and controls were 0.70 +/- 0.07 and 0.60 +/- 0.03,
      respectively. The difference was significant (p < 0.001). Pulsatility indexes in
      the study and controls were 1.07 +/- 0.34 and 0.98 +/- 0.23, respectively. The
      difference was not significant (p > 0.005). Significant difference was also
      noticed in the parenchymal widths between both groups (p < 0.001). CONCLUSION: It
      appeared that intrarenal color Doppler sonography can provide physiologic
      information reflecting renal vascular resistance status by means of an easily
      obtained parameter: resistive index.

PMID- 8740036
TI  - Aetiology, diagnosis and management of spontaneous perirenal haematomas.
AB  - This study focuses on the diagnostic and therapeutic challenge posed by
      spontaneous perirenal haematomas (SPHs). The medical records of 18 patients with
      SPHs seen in the past 8 years were reviewed with respect to aetiology, diagnosis
      and therapeutic management. SPH was secondary to angiomyolipoma (n = 4),
      polycystic kidneys (n =4), panarteritis nodosa (n = 3), renal cell carcinomas
      (RCCs, n = 2), glomerulonephritis, pyelonephritis, Morbus Wegener and cortical
      adenoma (one each). One case remained unclear. With appropriate imaging
      techniques (computed tomography and angiography) the underlying disorder was
      detected in 72%; in 4 cases the diagnosis was revealed by exploration and biopsy.
      Surgery was necessary in 16 patients. The cause of bleeding can be revealed by
      appropriate imaging in most cases. When imaging procedures fail to reveal the
      cause of SPH, exploration and biopsy are mandatory to exclude RCC. If the cause
      of SPH remains unclear even after exploration, patient monitoring by CT is
      justified.

PMID- 8740037
TI  - Follow-up of the remaining bladder after supravesical urinary diversion.
AB  - OBJECTIVES: To review our experience in 14 patients who underwent supravesical
      urinary diversion maintaining their defunctionalized bladder in situ. METHODS: A
      variety of pathological entities indicated surgery, including neurogenic bladder,
      urinary tuberculosis (with severely contracted bladder), interstitial cystitis,
      and retroperitoneal fibrosis. RESULTS: Global analysis revealed a total of 11
      patients (78.5%) who presented complications, the most frequent being
      mucopurulent and bloody secretions (28.5%), and painful bladder spasms (14.2%),
      followed by hemorrhage, pyocystis, hypogastric or urethral pain, and sepsis.
      CONCLUSION: Two patients (14.2%) required hospitalization for treatment of
      complications. The majority of complications were treated successfully with
      bladder irrigations and antibiotics. One patient required total cystectomy
      secondary to pyocystis.

PMID- 8740038
TI  - Carboplatin monochemotherapy in elderly patients with nonoperable transitional
      cell carcinoma of the bladder: a two-stage, phase II study.
AB  - Elderly patients with nonoperable transitional cell carcinoma of the bladder need
      a rather active, but less toxic treatment than full-dose polychemotherapy. This
      study was designed to determine whether the cisplatin-analogue carboplatin (which
      is less nephrotoxic and less neurotoxic than the parent compound) has sufficient
      activity against T2-T4 neoplasms (both nonmetastatic and metastatic) to warrant
      further development in phase III trials. Carboplatin dose was adjusted according
      to creatinine clearance, with a maximum dose of 300 mg/m2. The patient selection
      for this screening for activity was adjusted by the use of the 'optimal' two
      stage design. Seventeen patients were enrolled, with a median age of 78 years
      (range: 70-85), a median performance status of 80% (range: 70-90%); 13 patients
      were lymph node-negative (10 T2, 2 T3, 1 T4) and 4 had locoregional or distant
      node metastases. Nine patients had a complete response (3 in the first, 9
      patient, stage, and 6 in the second, 8-patient, stage), demonstrating that
      carboplatin had sufficient activity (at the 'desirable' target level of 35%);
      almost all responses were observed in T2 patients. Six patients had stable
      disease, and 2 had disease progression during treatment. The toxicity was
      acceptable, with only 41% of patients having grade II-III hematologic toxicity.
      More than 30% of patients were estimated to be free from progressive disease (54%
      alive) at 24 months. In our opinion carboplatin is suitable to be tested-in a
      phase III testing versus full-dose radiation therapy-as adjuvant after initial
      transurethral resection of the prostate in elderly patients with T2 transitional
      cell carcinoma of the bladder considered radically nonoperable for medical
      problems.

PMID- 8740039
TI  - Diagnosis and treatment of enterovesical fistula.
AB  - The records of 24 patients with enterovesical fistula treated at the urology
      sections of Telemark and Vestfold Central Hospitals are presented. Most fistulas
      were due to diverticulitis or a malignant tumor. The part of the intestine most
      frequently affected was the sigmoid colon in 14 patients, the rectum in 3, the
      cecum in 2 and the small intestine in 2. Of the 21 patients operated on, 12
      underwent a one-stage procedure with resection of the fistula and primary
      anastomosis of the intestine. The postoperative course was uneventful for 16
      patients. Recurrence of the fistula occurred in 1 patient. Three patients were
      conservatively treated. We recommend a one-stage operation for patients in a good
      general operating condition, with a well-organized fistula and no systemic
      infection.

PMID- 8740040
TI  - Effects of haloperidol in a response-reinstatement model of heroin relapse.
AB  - The present study employed an animal model of drug relapse in which previously
      extinguished heroin self-administration behavior was reinstated following a
      single reinforced trial. Male albino rats were trained to traverse a straight
      alley for a reinforcer consisting of a single IV injection of 0.06 mg/kg
      diacetylmorphine (heroin). Once the alley-running had been established, the
      heroin reinforcer was removed and the operant behavior permitted to extinguish
      over trials. On treatment day, animals were injected 45 min prior to testing with
      0.0, 0.075, 0.10, 0.15 or 0.3 mg/kg of the dopamine receptor antagonist,
      haloperidol. A single trial was then conducted during which some animals
      continued to experience extinction conditions while others were injected with the
      heroin reinforcer upon entry into the goal box. The effects of these
      manipulations were determined during an additional single test trial conducted 24
      h later when the subjects were no longer drugged. While heroin produced a
      reliable reinstatement in operant responding, this effect was dose-dependently
      prevented by pretreatment with haloperidol. These data suggest that dopamine
      receptor antagonism alters the reinforcing consequences of heroin administration
      as measured by heroin's ability to reinstate operant behavior following a
      prolonged period of nonreinforced responding.

PMID- 8740041
TI  - The effects of dopamine D1 and D2 receptor antagonists on the rewarding effects
      of delta 1 and delta 2 opioid receptor agonists in mice.
AB  - The effects of the dopamine D1 antagonist SCH23390 and the D2 antagonist
      sulpiride on the rewarding effects of delta opioid receptor agonists were
      examined in mice. Both [D-Pen2, Pen5]enkephalin (DPDPE, 1-15 nmol, ICV), a
      selective delta 1 opioid receptor agonist, and [D-Ala2]deltorphin II (DELT, 0.5-5
      nmol, ICV), a selective delta 2 opioid receptor agonist, produced a dose
      dependent place preference in mice. The DPDPE (15 nmol, ICV)-induced place
      preference was abolished by BNTX (0.5 mg/kg, SC), a delta 1 opioid receptor
      antagonist, but not by NTB (0.5 mg/kg, SC), a delta 2 opioid receptor antagonist.
      In contrast, the DELT (5 nmol, ICV)-induced place preference was antagonized by
      NTB, but not BNTX. Pretreatment with SCH23390 (3 micrograms/kg, SC) abolished the
      DPDPE-induced place preference, but not affect the DELT-induced place preference.
      Moreover, pretreatment with sulpiride (40 mg/kg, SC) did not modify the place
      preference induced by DPDPE or DELT. In the present study, we found that the
      activation of both central delta 1 and delta 2 opioid receptors produced
      rewarding effects. Furthermore, these results suggest that the rewarding effects
      of delta 1 opioid receptor agonist may be produced through activation of the
      central dopaminergic system, especially dopamine D1 receptors, whereas the
      rewarding effects of delta 2 opioid receptor agonists may be produced by some
      other mechanism(s).

PMID- 8740043
TI  - Randomized, double blind, controlled placebo-phase in trial of low dose
      phenelzine in the chronic fatigue syndrome.
AB  - Because of the striking similarity of the clinical manifestations produced by use
      of the drug reserpine and seen in patients with the chronic fatigue syndrome
      (CFS), we theorized that CFS was a disorder of reduced central sympathetic drive.
      Because of the pharmacology of control of this central sympathetic system, we
      further postulated that CFS symptoms would respond quickly to low dose treatment
      with a monamine oxidase inhibitor. To test these hypotheses, we designed a
      randomized, double blind placebo controlled study using phenelzine. No patient in
      the trial had a diagnosis of lifetime or current psychiatric disorder and none
      had depressed mood in the range of clinically depressed patients on a paper and
      pencil test of depression. Patients in the placebo group received placebo for 6
      weeks while those in the drug treatment group were treated in three 2-week
      segments-placebo, 15 mg phenelzine every other day, and then 15 mg daily. This
      treatment regimen produced a significant pattern of improvement compared to
      worsening in 20 self report vehicles of CFS symptoms, illness severity, mood or
      functional status. Thus the data support our hypothesis of reduced sympathetic
      drive, although an alternative hypothesis of pain alleviation is also possible.
      The study design also allowed us to evaluate patients for a placebo effect: no
      evidence for this was found, suggesting that CFS is not an illness due to
      patients' being overly suggestible.

PMID- 8740042
TI  - Comparative behavioral sensitization to stereotypy by direct and indirect
      dopamine agonists in CF-1 mice.
AB  - The present experiments were designed to compare the properties of behavioral
      sensitization induced by the indirect agonists, amphetamine and cocaine, to that
      induced by the direct dopamine agonists, apomorphine and PPHT. Both classes of
      agonist produced sensitization when administered either in relatively low daily
      doses or in a single high dose. Mice sensitized to the indirect agonists were
      cross-sensitized to the direct agonists and vice versa. A pharmacological
      evaluation of the sensitization induced by the two types of agonist demonstrated
      both similarities and dissimilarities. Induction to the indirect agonists is
      blocked by CPP, DNQX and diltiazem, whereas only CPP and diltiazem blocked
      induction to the direct agonists. Furthermore, although none of these antagonists
      block the expression of sensitization by the direct agonists, all three were
      previously shown to block the amphetamine expression of sensitization. Striking
      differences were also observed in the persistence of the sensitization induced by
      the two types of agonists. While the indirect agonist-induced sensitization is
      long lasting, the direct agonist-induced sensitization is relatively short-lived.
      Furthermore, cross-sensitization of PPHT in amphetamine-sensitized animals was
      also short-lived, as was amphetamine cross-sensitization in PPHT-sensitized
      animals. The data suggest that the induction of sensitization consists of two
      separable mechanisms, one for induction per se, the other for persistence.

PMID- 8740045
TI  - Reflexes of the cutaneous microcirculation in amitriptyline and in fluoxetine
      treated patients.
AB  - Cutaneous microcirculation was investigated in 30 major depressed inpatients
      receiving either 150 mg amitriptyline (n = 15) or 30 mg fluoxetine (n = 15) as
      monotherapy, and in 15 normal control subjects matched for age and sex. The laser
      Doppler flux (LDF) was recorded while resting and under the condition of a sudden
      deep breath ("inspiratory gasp response"). In normal subjects this autonomic
      function test caused a marked decrement of LDF signal, which rapidly returned to
      the baseline value. In both groups of drug treated patients the decrements of LDF
      signal after a sudden deep breath did not differ from those found in the normal
      control subjects. However, in the amitriptyline-treated patients the return of
      LDF-signal to the baseline values was significantly delayed (P = 0.0007), while
      patients treated with fluoxetine showed the same behaviour as normal subjects.
      With a discriminant analysis using the results of the inspiratory gasp responses,
      100% of the amitriptyline treated patients were correctly classified. Since both
      groups of depressed patients revealed comparable depression scores, the
      differences found are probably due to the side effects of amitriptyline. Possible
      clinical implications of these findings are discussed.

PMID- 8740044
TI  - Behavioural effects in the rat of the putative dopamine D3 receptor agonist 7-OH
      DPAT: comparison with quinpirole and apomorphine.
AB  - This study assessed the effects of IP injections of (+/-) 7-hydroxy-2(N,N-di-n
      propylamino)tetralin (7-OH-DPAT), a dopamine agonist that has been reported to
      have preferential affinity for the dopamine D3 sub-type of receptor, on four
      behavioural procedures in the rat: 1) spontaneous locomotion, 2) electrical self
      stimulation of the ventral tegmental area (VTA), using the curve-shift procedure
      3) operant responding for food under a progressive-ratio (PR) schedule and 4)
      induction of stereotypies. The effects of (+/-) 7-OH-DPAT were compared to the
      effects of apomorphine, a non-specific DA agonist, and quinpirole, a selective
      D2/D3 agonist. All three dopamine agonists decreased locomotor activity at low
      doses (0.01-0.3 mg/kg), and only apomorphine had clear locomotor stimulant
      effects at the highest dose tested (3 mg/kg). The three drugs dose-dependently
      depressed VTA self-stimulation in a similar way, with low doses inducing a fairly
      parallel rightward shift of the frequency/rate curves and higher doses flattening
      the curves. In contrast, responding for food under the PR schedule appeared to be
      differentially affected by the three agonists: 7-OH-DPAT induced a biphasic
      effect, with a maximal decrease in lever-pressing at 0.1 mg/kg, followed by a
      return to baseline levels with increasing doses (0.3-3 mg/kg); quinpirole showed
      a tendency to decrease responding over the whole dose-range tested with a maximal
      effect of about 50% of baseline between 0.25 and 1 mg/kg, and apomorphine dose
      dependently decreased responding, with rats ceasing to respond at 0.3 mg/kg. All
      three DA agonists induced stereotypies, but there was a difference in the maximal
      stereotypy score induced by each of the ligands: 7-OH-DPAT produced a lower
      maximal effect than quinpirole or apomorphine. This indicates that each of the
      three dopamine agonists preferentially induced different types of stereotypies.
      Together, these data suggest that the putative dopamine D3 agonist 7-OH-DPAT, at
      low doses, has depressant effects similar to those induced by low doses of the
      other two DA agonists. Differences in the behavioural effects of higher doses
      were, however, mostly observed in two procedures, PR responding and induction of
      stereotypies.

PMID- 8740047
TI  - Oxygen administration enhances memory formation in healthy young adults.
AB  - Despite numerous studies indicating that transient cerebral oxygen depletion has
      a detrimental effect on cognition, surprisingly little research has examined the
      possibility of cognitive enhancement following elevated oxygen levels in healthy
      adults. Here, we present evidence demonstrating that oxygen administration
      improves memory formation. Inhalation of oxygen immediately prior to learning a
      word list resulted in a significant increase in mean number of words recalled 10
      min later, compared to subjects who inhaled oxygen immediately prior to recall or
      to controls who underwent no intervention. In a second experiment, the learning
      test interval was increased to 24 h and, again, only pre-learning (but not pre
      test) oxygen administration resulted in significant memory facilitation. In
      experiment 3, inhalation of oxygen prior to learning was compared to inhalation
      of compressed air, oxygen (but not compressed air) resulted in a significant
      increase in word recall 24 h later. In no experiment did oxygen have a
      significant effect on any mood item measured. We interpret these data as
      indicating that increased availability of cerebral oxygen facilitates cognition,
      including memory consolidation. The implications for the psychopharmacology of
      cognitive enhancement are considered in the context of cholinergic systems and
      neural metabolism.

PMID- 8740046
TI  - The use of the rat elevated plus-maze to discriminate between non-selective and
      BZ-1 (omega 1) selective, benzodiazepine receptor ligands.
AB  - The behavioral effects of a wide range of BZ (omega) receptor ligands, including
      non-selective full (alprazolam, clorazepate, chlordiazepoxide and diazepam) and
      partial (bretazenil, imidazenil and Ro 19-8022) agonists, and selective BZ-1
      (omega 1) (abecarnil, CL 218,872, CL 284,846 and zolpidem) receptor ligands, were
      compared in the rat elevated plus-maze test. Behaviors recorded comprised the
      traditional indices of anxiety as well as a number of ethologically derived
      measures. In addition, the specificity of drug effects was evaluated by measuring
      spontaneous locomotor activity in activity cages in separate groups of animals.
      Results showed that all compounds tested not only increased the proportion of
      time spent and proportion of entries into the open arms of the maze (considered
      as traditional indices of anxiety) but also affected head-dippings and attempts
      at entry into open arms, which can be considered as indices of risk assessment
      responses. However, the magnitude of these effects was generally smaller with the
      BZ-1 (omega 1) selective agents. Moreover, additional differences were apparent
      on the total number of arm entries measure, which was significantly increased by
      most full and all partial agonists, but was unaffected by the selective BZ-1
      (omega 1) compounds. If it is assumed that total arm entries are contaminated by
      anxiety, the latter finding indicates a weaker anxiety-reducing potential of
      selective BZ-1 (omega 1) ligands. Importantly, the increase in total arm entries
      induced by the non-selective agents was not associated with a similar effect on
      locomotion as revealed in the actimeter. Finally, anxiolysis produced by the BZ-1
      (omega 1) ligands was invariably observed at doses which reduced locomotor
      activity, suggesting that the anxiolytic-like effects of these compounds are
      confounded by decreases in locomotor activity.

PMID- 8740048
TI  - Effects of the novel NMDA-receptor antagonist SDZ EAA 494 on memory and attention
      in humans.
AB  - Effects of the novel competitive N-methyl-D-aspartate (NMDA)-receptor antagonist
      SDZ EAA 494 were investigated on memory and attention in humans. SDZ EAA 494 was
      administered either as single doses at a dose range of 1-50 mg, or as multiple
      doses over the course of 1 week at doses of 25 mg once or twice daily. Selected
      cognitive functions were assessed at baseline, 2 and 4 h after single dose
      administration, and at baseline, 2, 4 and 8 h on days 1 and 7 of multiple dose
      administration. The assessments included simple and complex reaction time tests
      to assess attention, and verbal, non-verbal and spatial memory tests with
      immediate and late recall. Verbal and non-verbal memory test performance was
      significantly impaired at a dose level of 50 mg after single administration, and
      of 25 mg twice daily after multiple administration, without concomitant
      significant impairment of reaction time. Spatial memory test performance was not
      significantly affected. The maximum effect occurred 2 h postmedication and was
      more pronounced after repeated administration. These results suggest that the
      inhibition of NMDA-receptors in humans may impair memory processes.

PMID- 8740049
TI  - Effects of chronic treatment with zimelidine and REM sleep deprivation on the
      regulation of raphe neuronal activity in a rat model of depression.
AB  - Electrophysiological investigations on the mechanism of action of antidepressants
      have shown that both deprivation of rapid eye movement (REM) sleep and chronic
      treatment with antidepressants render serotoninergic (5-HT) neurons less
      sensitive to the inhibitory effect of 5-HT reuptake blockers in the rat. It was
      of interest to test whether the same mechanisms could be evidenced in a possible
      experimental model of depression. The latter consisted of rats which had been
      treated neonatally with clomipramine and exhibited at adult age behavioural and
      sleep alterations which resemble the human disorder. Recording the
      electrophysiological activity of 5-HT neurons in the nucleus raphe dorsalis (NRD)
      revealed that both chronic treatment with zimelidine and REM sleep deprivation
      induced a hyporeactivity of these neurons to the inhibitory effect of citalopram
      in "normal" rats. However, in rats which had been treated neonatally with
      clomipramine, 5-HT neurons were hyporeactive to the effect of this 5-HT reuptake
      blocker already under baseline conditions, and no further modification could be
      induced by chronic zimelidine administration or REM sleep deprivation. It can be
      hypothesized that adaptive phenomena at the serotoninergic NRD level are not a
      relevant element to explain the mechanism of action of anti-depressants in the
      present model of depression, while they have been considered as a crucial event
      in "normal" rats.

PMID- 8740050
TI  - Twelve-hour brain lithium concentration in lithium maintenance treatment of manic
      depressive disorder: daily versus alternate-day dosing schedule.
AB  - The 12-h brain lithium concentration was measured by lithium-7 magnetic resonance
      spectroscopy in ten manic-depressive patients receiving daily or alternate-day
      lithium carbonate treatment. The median dose of lithium carbonate was 800 mg in
      the daily treatment group and 1200 mg in the alternate-day group. Median 12-h
      serum lithium concentration in the two groups was 0.86 mmol l-1 and 0.55 mmol l
      1, respectively, while the corresponding concentration in brain was 0.67 mmol l-1
      and 0.52 mmol l-1, respectively. The 12-h brain lithium concentration was
      independent of lithium dosing schedule (multiple linear regression), but
      correlated significantly with the 12-h serum lithium concentration (P = 0.003; B
      = 0.53, 95% c.l. 0.24-0.82; beta = 0.83). Thus at identical 12-h serum lithium
      concentrations the 12-h brain lithium concentration is similar with both
      treatment regimes. As the risk of manic-depressive relapse during alternate-day
      lithium treatment is in our experience 3-fold greater than with daily treatment
      (at similar mean 12-h serum lithium concentration), the findings suggest that the
      difference in the prophylactic efficacy of the two dosing schedules is unrelated
      to differences in the 12-h brain lithium concentration.

PMID- 8740051
TI  - Behavioral sensitization is induced by intravenous self-administration of cocaine
      by rats.
AB  - Rats were prepared with jugular catheters and assigned randomly to one of three
      groups: intravenous (IV) self-administration of cocaine, yoked administration of
      cocaine or vehicle. Rats experienced intermittent administration of cocaine (0.75
      mg/kg per injection) or vehicle (0.1 ml/injection) for six test sessions, in
      accordance with the pattern of injections made by the self-administration group.
      Sensitization of motor activity between pre-and post-treatment challenges of
      cocaine (3 mg/kg, IV) was observed after both self- and yoked administration of
      cocaine but not in the yoked-vehicle group. These data indicate that
      sensitization as a consequence of drug self-administration may be an important
      factor in the etiology of addiction.

PMID- 8740052
TI  - Examining the relation between usual-brand nicotine yield, blood cotinine
      concentration and the nicotine- "compensation" hypothesis.
AB  - Eight data sets relating usual-brand nicotine yield (FTC method or equivalent) to
      blood cotinine concentration are reviewed with respect to the so-called nicotine
      "compensation" hypothesis, i.e., that all smokers achieve a specific level of
      nicotine in their blood, regardless of the FTC nicotine yield of the cigarette
      smoked. The data from the studies reviewed here indicate wide variability in
      blood cotinine concentrations over the range of FTC nicotine yields and that the
      nicotine-compensation hypothesis is not supported. On average, blood cotinine
      concentrations are found to be roughly midway between complete compensation (all
      smokers absorb equal amounts of nicotine regardless of FTC nicotine yield) and
      the value expected if there was no compensation (i.e., smokers absorb an amount
      of nicotine exactly equal to the FTC yield). As a result of individual smoking
      behavior differences (number of cigarettes smoked, puff volume, puff frequency
      inhalation volume and depth, etc.), the data indicate that, on average, smokers
      achieve roughly 50% lower blood cotinine concentrations than predicted by the
      nicotine-compensation hypothesis.

PMID- 8740054
TI  - Equithesin without chloral hydrate as an anaesthetic for rats.
AB  - In 1977 it was reported that chloral hydrate could cause adynamic ileus in rats,
      leading to morbidity and death. The symptoms were a swollen abdomen, lethargy and
      anorexia. However, chloral hydrate is still used as an anaesthetic, particularly
      in Equithesin mixture. We report that Equithesin without chloral hydrate is an
      effective anaesthetic, with a slightly reduced potency compared to Equithesin
      itself, and anaesthesia may be maintained for several hours by supplemental
      doses.

PMID- 8740053
TI  - Prolactin plasma levels and D2-dopamine receptor occupancy measured with IBZM
      SPECT.
AB  - By the application of 123([123I]IBZM), an iodine-labelled dopamine D2-receptor
      antagonist, brain D2 receptors in humans can be visualized with single photon
      emission computed tomography (SPECT). The ratio of IBZM binding to striatal
      regions versus binding to frontal cortex (ST/FC ratio) provided a
      semiquantitative measurement of D2 receptor binding in the striatum. This study
      investigated the relationship between receptor occupancy and plasma prolactin
      levels in 12 male patients treated with haloperidol, benperidol or clozapine.
      Prolactin levels were positively correlated with D2 receptor occupancy,
      reflecting at least in part a comparable dopamine receptor antagonism in
      different dopaminergic pathways.

PMID- 8740055
TI  - Are benzodiazepines antidepressants?

PMID- 8740056
TI  - Reoperation after failed antireflex surgery. Review of 101 cases.
AB  - Between January 1970 and July 1994, 101 patients underwent reoperation for a
      failed antireflux procedure. These patients had previously had 160 upper
      gastrointestinal tract operations, usually a Nissen fundoplication or one of its
      modifications (87). The chief reason for failure of the original antireflux
      procedure was faulty surgical technique (65). An incorrect diagnosis accounted
      for most of the remaining failure (22). Of patients who had follow-up studies,
      80% were improved by reoperation, which consisted of takedown or refashioning of
      the original wrap in the majority of patients (63). A more radical approach is
      justified after two failed reoperations. Our current preference is for vagotomy,
      antrectomy, and Roux-en-Y diversion coupled, when indicated, with resection of
      the esophagogastric junctional area.

PMID- 8740057
TI  - Quality of life after surgical therapy of bronchogenic carcinoma.
AB  - Quality of life (QL) after the "curative" resection of non-small cell
      bronchogenic carcinoma was assessed by patients using the EORTC QL questionnaire
      (QLQ) and by a psychologist using the Spitzer Index. Quality of life was assessed
      in 52 patients on one occasion 12 months postoperatively and in 20 patients
      regularly starting with a preoperative assessment. Self- and external evaluation
      showed a significant correlation (r = 0.41), but QL was assessed as being higher
      by the external observer. After surgery it was mainly affected by restrictions
      related to physical activities, job and household tasks, and disease symptoms,
      whereas limitations in emotional, social, and financial domains were found less
      frequently and less severely. Of the different medical (surgical procedures,
      tumor recurrence) and social factors (sex, marital and employment status), only
      tumor recurrence was determined to have a significant and negative influence on
      postoperative QL (P < 0.02). When compared to the preoperative assessment, QL had
      deteriorated on discharge from hospital but was restored within 3-6 months
      postoperatively in disease-free patients.

PMID- 8740058
TI  - Completion pneumonectomy. A retrospective analysis of indications and results.
AB  - Between 1970 and 1993, 446 patients underwent pneumonectomy. Completion
      pneumonectomy was performed in 37 patients (8.3%): 34 men and 3 women, with a
      mean age of 61 years (range 20-78 years). Indications were benign disease in 4
      patients and carcinoma in 33. Of the latter, 21 patients underwent resection for
      metachronous lung cancer, 6 for recurrent lung cancer, 4 for previous incomplete
      resection, 1 for primary lung cancer after previous resection for benign disease
      and 1 patient after previous segmentectomy for metastasis. The mean interval
      between first operation and completion pneumonectomy was 41 months (range 1-187
      months) for the whole group, 30 months for benign disease and 42 months for
      carcinoma. The overall operative mortality was 6/37 (16.2%); 1/4 patients with
      benign disease and 5/33 (15.2%) patients with carcinoma. Nine patients (29%) had
      one or more major non-fatal complication. Actuarial 3- and 5-year survival rates
      were 41.0% and 24.5% for the entire group, 75% at both times for patients with
      benign disease, 36.4% and 18.3% for all patients with carcinoma at the time of
      completion pneumonectomy and 24.3% and 14.5% for patients with metachronous or
      recurrent lung cancer. For 15 patients with stage I or II metachronous lung
      cancer, the 3- and 5-year survival rates were 33.9% and 16.9%. All six patients
      with stage III metachronous cancer died within 18 months. In conclusion,
      completion pneumonectomy carries a high operative mortality and morbidity. Long
      term survival is negatively influenced by stage III lung cancer.

PMID- 8740059
TI  - Pulmonary embolism: a frequent cause of acute fatality after lung resection.
AB  - Between 1975 and 1993, lung resections were performed in 1735 patients because of
      malignancies, with an early postoperative mortality of 7.2% (125 patients). Early
      postoperatively acute cardiorespiratory failure was experienced by 32 patients
      (1.85%), of whom 26 died despite immediate resuscitation measures. In 20/26
      patients autopsy was performed revealing central pulmonary embolism as the cause
      of death in 19 of them. In one patient a rupture of the free posterior left
      ventricular wall following transmural myocardial infarction was found. Two
      patients who could be resuscitated successfully were operated on with
      extracorporeal circulation after pulmonary angiography had been performed to
      confirm the diagnosis; however they died 2 days later of right heart failure. Of
      the survivors three cases had myocardial infarctions, one patient had arrhythmias
      of unknown etiology. Immediate embolectomy with the use of extracorporeal
      circulation was performed in two patients, only on the ground of suspected
      pulmonary embolism and without further diagnostic measures. Both patients
      survived. Of the 23 cases, with proven pulmonary embolism 17 were still under
      postoperative prophylaxis with heparin. Six patients were already fully
      mobilized. We conclude that massive pulmonary embolism is a frequent early
      postoperative fatal complication after lung resections, which cannot be safely
      prevented by postoperative heparinization. The only successful life-saving
      measure in the case of central pulmonary embolism is immediate pulmonary
      embolectomy, if necessary without further diagnostic measures.

PMID- 8740060
TI  - Valve surgery combined with coronary artery operation: is the use of internal
      mammary artery a predictor for early complications?
AB  - The internal mammary artery (IMA) provides better early and long-term patency
      than venous grafts do. Although IMA is the conduit of choice in isolated coronary
      artery bypass grafting (CABG), its use in combined procedures is not routine in
      some cardiovascular units. During a 16-month period, 188 patients underwent valve
      surgery combined with CABG. Internal mammary grafts were used in 68/188 (36%)
      patients (group 1) and vein grafts without arterial grafts (group 2) in 120/188
      (64%). Left IMA was implanted in 67/68 (99%) and right IMA in 1/68 1%) cases.
      Surgeon A used IMA in 28/44 (64%), surgeon B in 20/32 (63%), surgeon C in 18/44
      (41%), surgeon D in 1/4 (25%) and surgeon E in 1/63 (2%) patients. The final
      decision to use IMA in a combined procedure was left up to the surgeon.
      Statistically, the preoperative- and perioperative data were identical in the two
      groups, although the frequency of IMA grafting in patients with double valve
      replacement and reoperation was lower (1/68 vs 11/120, ns, and 3/68 vs 9/120,
      ns). Ten of 188 (5.3%) patients died within 30 days after operation. Longer cross
      clamp time (P = 0.008) and mitral valve replacement (P = 0.05) were independent
      risk factors for early death. The use of IMA did not increase the risk of early
      mortality. The postoperative variables were similar in the IMA and vein groups,
      in particular data suggesting perioperative myocardial infarction (CK-MB,
      catecholamine support). Postoperative mechanical ventilation was longer in the
      IMA group, although not significantly (P = 0.06). Early mortality and morbidity
      were identical in the two groups in combined procedures. We did not find any
      hints for an increased risk of using IMA in this type of surgery. Internal
      mammary artery implantation is safe in selected patients undergoing combined
      valve and CABG surgery. Beside the better long-term patency of IMA, its use may
      have several technical advantages.

PMID- 8740061
TI  - Transcranial Doppler detection of microemboli in prosthetic heart valve patients:
      dependency upon valve type.
AB  - Transcranial Doppler ultrasound has revealed the existence of cerebrovascular
      microemboli in asymptomatic patients with prosthetic heart valves. We
      investigated the relation between the presence and number of emboli signals and
      valve type. Patients with six types of prosthetic valves (Bjork-Shiley monostrut,
      Medtronic-Hall, Carbomedics, ATS, Carpentier-Edwards standard, Carpentier-Edwards
      supraannular) were examined using transcranial Doppler ultrasound in two centers.
      The monitoring time was 30 min over the right middle cerebral artery. All
      patients were stabilized on warfarin at the time of study. Microemboli signals
      were identified by their characteristic audiovisual signal and on subsequent
      spectral analysis, based on accepted criteria. A standard neurologic
      questionnaire was completed by all patients. The prevalence of microemboli
      signals varied between 49% (Medtronic Hall) and 97% (Bjork-Shiley monostrut),
      while their number varied between 1 [0-3] (Carpentier-Edwards standard) and 187
      [136-240] (Bjork-Shiley monostrut) per hour (median and 95% CI). Both parameters
      were significantly higher in patients with Bjork-Shiley monostrut valves compared
      to the other patient groups. There were no significant differences in the
      prevalence of neurologic complications among the groups examined (overall 16%),
      or in emboli numbers between symptomatic and asymptomatic patients. The
      prevalence and quantity of microemboli signals in patients with prosthetic heart
      valves, as detected by transcranial Doppler, is dependent upon valve type. The
      clinical significance of these microemboli signals remains to be further
      evaluated.

PMID- 8740062
TI  - Long-term results of heart transplantation deteriorate more rapidly in patients
      over 60 years of age.
AB  - It is generally agreed that the upper age limit for heart transplantation is 60
      years. However, an increasing number of elderly candidates are accepted for heart
      transplantation. We retrospectively analyzed our experience with a total of 204
      consecutive transplantations, performed in 195 adult patients (9
      retransplantations) between March 1987 and September 1993. There were 48 patients
      older than 60 years (mean 62.9 +/- 3), group I (gr I) and 156 patients between 20
      and 59 years old (mean 47.5 +/- 8), group II (gr II). The two groups were matched
      for sex-ratio (female 10.4 vs 14.2%), indications (cardiomyopathy, ischemic,
      others), and hemodynamic parameters (pulmonary artery pressure, capillary wedge
      pressure, cardiac index). A ventricular assist device was used in 14 patients as
      bridge to transplantation in gr II vs 0 to gr I. There were seven early deaths in
      gr I (14.6%) vs 14 in gr II (8.97%, NS). A total of 183 survivors (41 vs 142)
      have been followed up for 1 month-6.3 years (mean follow-up 20.4 +/- 19.3 months
      in gr I, 35.4 +/- 23 in gr II). No patient was lost to follow-up. There were 11
      late deaths in gr I vs 16 in gr II. The most common cause was malignancy (n = 4)
      in gr I and sudden death (n = 9) in gr II, with a significant difference. The
      actuarial survival was 68.8% in gr I vs 88.5% in gr II at 1 year 43.5% in gr I vs
      76.4% in gr II at 5 years. In conclusion, transplanted patients over 60 years of
      age have a significantly poorer late survival than younger patients, despite
      similar good early results. Moreover, the causes of late deaths were different in
      the two groups. So, heart transplantation in patients over 60 years of age should
      be carefully considered.

PMID- 8740063
TI  - Aortic wall structural strengthening by intraluminal net prosthesis to arrest
      aneurysm progression and to prevent dissection and rupture.
AB  - The major limitation implicit in the endovascular procedures for aortic
      prosthetic substitution is that they cannot be used in those tracts of the aorta
      where important collateral branches originate (aortic arch, thoraco-abdominal
      tract, upper abdominal), that would be occluded by the prosthesis. In order to
      overcome this limitation we hypothesized the endovascular positioning of a
      prosthesis in the form of a wide mesh network that would be gradually and
      spontaneously covered by new intima and included in the aortic wall. The fabric
      framework linked to the aortic wall would then condition its significant, regular
      and uniform mechanical strengthening that fractionates and partially absorbs the
      centrifuge pulsatile stress of the bloodstream. The purpose of this paper is to
      report the results of the insertion of a braided Prolene net prosthesis in the
      first 7 cm of the descending aorta of ten swine. The animals were killed after 6
      weeks, the substituted segment removed and aortic wall compliance measured under
      standardized conditions. The prosthesis was found entirely covered by new intima,
      well embodied in the aortic wall. The intercostal collateral included in the
      substituted segment was patent, as proved by bubble formation during underwater
      insufflation. Compliance of the prosthesis segment was significantly lower than
      that of the adjacent descending aorta. Histology showed a regular net prosthesis
      inclusion deep in the neo-intima layer. Present results indicate the technical
      feasibility of the procedure, achieving significant aortic wall strengthening
      without affecting the collateral (intercostal) circulation.

PMID- 8740064
TI  - Influence of hepatic mitochondrial redox state on complement biosynthesis and
      activation during and after cardiopulmonary bypass operations.
AB  - We have proposed the hazardous phenomena associated with cardiopulmonary bypass
      (CPB) are due to metabolic derangement by hepatic mitochondrial dysfunction
      during and after CPB. On the contrary, complement activation and consumption
      during CPB is reported to be related to the morbidity associated with cardiac
      surgery. To determine the significance of the hepatic mitochondrial function on
      the morbidity of cardiac surgery, we measured the serum levels of complements (C3
      and C4), activated complements (C3a and C4a), and the arterial ketone body ratio
      (AKBR), which reflects the hepatic mitochondrial redox state, in 30 patients
      undergoing CPB. The AKBR, which was at a normal level preoperatively, dropped to
      a critical level after the initiation of CPB and remained at a low level during
      the CPB, returning to the preoperative level on the second postoperative morning
      in a time dependent fashion. The patients group were assigned to two groups
      according to their AKBR on the first postoperative morning. Group I consisted of
      patients whose AKBR had recovered to above 0.7 on the first postoperative morning
      (n = 16). Group II consisted of the rest of the patients (n = 14). The serum
      complement concentration had considerably decreased by the end of bypass, but
      recovered in a time-dependent fashion after CPB. The group I patients (C3: 71% of
      its preoperative value, C4: 85% of its preoperative value) recovered their
      complements more quickly than the group II patients (C3: 56% of its preoperative
      value, C4: 54% of its preoperative value). However, the serum C3a and C4a
      concentrations increased by the end of bypass (C3a: 806% of its preoperative
      value, C4a: 341% of its preoperative value). The activated complements were
      significantly higher in the group II patients (C3a: 124% of its preoperative
      value, C4a: 236% of its preoperative value) than in the group I patients (C3a:
      75% of its preoperative value, C4a: 113% of its preoperative value) on the first
      postoperative morning. It is suggested that hepatic mitochondrial function is
      related to recovering the complements and to reducing the activated complements
      after CPB.

PMID- 8740065
TI  - Patterns of changes in neutrophil adhesion molecules during normothermic
      cardiopulmonary bypass. A clinical study.
AB  - The adhesion of activated neutrophils to endothelial cells is a key feature of
      the inflammatory response to cardiopulmonary bypass (CPB) because it "unlocks" a
      cascade of cytotoxic events. This adhesion is made possibly by the sequential
      involvement of two sets of neutrophil cell surface receptors: L-selection and
      beta 2 integrins (CD 11 a/CD 18; CD 11 b/CD 18; CD 11 c/CD 18). We have assessed
      the changes in the expression of these adhesion molecules in ten patients who
      underwent various open-heart procedures with the use of "warm" (33.4 degrees-37
      degrees C) CPB. Arterial blood samples were obtained before, during and after
      bypass and processed for immunofluorescent flow cytometric analysis. CD 11 a
      expression remained unchanged throughout the study period. Conversely, CD 11 b
      drastically increased early after the onset of bypass (at 15 min on bypass: 172
      +/- 17 [mean fluorescence (arbitrary units), mean +/- SEM] versus 63 +/- 13
      before bypass. P < 0.02) and was still markedly elevated 30 min after the end of
      bypass (160 +/- 38, P < 0.05 versus the pre-by-pass value). CD 11 c expression
      underwent a similar upregulation (at 15 min of bypass: 54 +/- 5 versus 34 +/- 5
      at baseline, P < 0.01). L-selectin expression did not change significantly during
      the period of observation. Put together, these results suggest that CPB is
      associated with an increased adhesive potential of neutrophils, which enhances
      their binding to the vascular endothelium and thereby initiates tissue damage
      through the release of cytotoxic mediators from adherent cells. Manipulation of
      integrin expression could therefore represent an effective means of alleviating
      the component of bypass-induced inflammatory tissue damage which is more
      specifically neutrophil-mediated.

PMID- 8740067
TI  - Intrapericardial paraganglioma.
AB  - We describe the case of an intrapericardial pheochromocytoma located in the
      anterior surface of the heart and spreading over the pulmonary trunk. Under
      cardiopulmonary bypass (CPB) the tumor was removed. "En bloc" resection of the
      anterior wall of the right ventricular infundibulum and the pulmonary trunk was
      performed, with implantation of a fresh aortic homograft in the pulmonary
      position to avoid free pulmonary regurgitation.

PMID- 8740066
TI  - The use of a Perma-Flow graft for coronary artery bypass surgery.
AB  - We report on our first clinical use of a Perma-Flow graft for coronary artery
      bypass surgery (CABG). It may well be that repeated successful use of this graft
      will offer a chance for revascularization to patients who might otherwise have
      been denied for lack of appropriate vessels.

PMID- 8740068
TI  - Accelerated aortic allograft fibrocalcification after right ventricular outflow
      tract reconstruction in pediatric patients: report of two cases.
AB  - Two cases are presented of accelerated aortic allograft fibrocalcification after
      right ventricular outflow tract (RVOT) reconstruction occurring within 2 months
      after surgery in a 5-year-old and 22-month-old. Potential determinants of early
      calcification, clinical management after implantation and surgical alternatives
      are discussed.

PMID- 8740069
TI  - Gastropexy simplifies the use of the right gastroepiploic artery for myocardial
      revascularization.
AB  - Surgical anterior and superior fixation to the diaphragam of a segment of the
      greater curvature of the stomach simplifies the technical performance of
      harvesting the right gastroepiploic artery for coronary bypass grafting.
      Gastropexy avoids objections to the use of this pedicled arterial graft, such as
      the prolonged dissection time, the limited length of the conduit and the
      potential damage when abdominal surgery is later required.

PMID- 8740070
TI  - The search for markers of endothelial injury during open heart surgery.

PMID- 8740071
TI  - Papers from the consensus conference on appropriate prosthetic technology for
      developing countries held in Phnom Penh, Kingdom of Cambodia, 5-10 June 1995.

PMID- 8740072
TI  - A review of the consensus conference on appropriate prosthetic technology in
      developing countries.

PMID- 8740073
TI  - USAID's War Victims' Fund.

PMID- 8740074
TI  - Report on ICRC technical orthopaedic programme for war disabled.

PMID- 8740075
TI  - The work of GTZ (Deutsche Gesellschaft fur Technische Zusammenarbeit GmbH).

PMID- 8740076
TI  - Handicap International.

PMID- 8740077
TI  - The rehabilitation of the amputee in the developing world: a review of the
      literature.

PMID- 8740078
TI  - Prosthetics in the developing world: a review of the literature.

PMID- 8740079
TI  - 1H-pyrazolo[4,3-d]pyrimidine-7(6H)-one and 5H-pyrazolo[4,3-d] 1,2,3-triazin-4(3H)
      one derivatives. Synthesis and in vitro biological activity at adenosine A1 and
      A2a receptors.
AB  - The affinity of newly synthesized 1H-pyrazolo[4,3-d] pyrimidine-7 (6H)- one (5a
      f) and 5H-pyrazolo[4,3-d]1,2,3,-triazin-4(3H)-one (6a-i) derivatives for A1 and
      A2a adenosine receptors was investigated in rat cerebral membranes. The compounds
      showed affinities in the micromolar range for both adenosine A1 and A2a
      receptors. In particular 5d was the most interesting compound and showed some
      degree of selectivity for the A1 receptor (Ki values being 2 mumol/l; A1/A2a
      ratio < 0.021). The present study provides useful information for a better
      understanding of the structure-activity relationships of antagonists at adenosine
      receptors.

PMID- 8740080
TI  - Effect of the novel high affinity choline uptake enhancer 2-(2-oxopyrrolidin-1
      yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b] quinolin-4-yl)acetoamide on
      deficits of water maze learning in rats.
AB  - The pharmacological properties of MKC-231 (2-(2-oxopyrrolidin-1-yl)-N- (2,3
      dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-yl) acetoamide, CAS 135463-81-9)
      in comparison with an acetylcholinesterase (AChE) inhibitor, tacrine (CAS 1684-40
      8) were studied. MKC-231(10(-10)-10(-6) moll) significantly increased high
      affinity choline uptake (HACU) when it was incubated with the hippocampal
      synaptosomes of ethylcholine mustard aziridinium ion (AF64A) treated rats, but
      not of normal rats. MKC-231 did not affect the AChE activity, [3H]- quinuclidinyl
      benzilate binding, and [3H]-pirenzepine binding. Oral administration of MKC-231
      (1-10 mg/kg) significantly improved the learning deficits in the Morris' water
      maze of AF64A-treated rats, but it did not produce any significant side effects,
      like tremor, salivation or hypothermia, which were observed in rats treated with
      high doses of tacrine. Tacrine (0.1-3 mg/kg p.o.) failed to ameliorate the
      learning deficits in AF64A-treated rats. These results suggest that MKC-231 is a
      novel and quite unique compound, which improves the memory impairment induced by
      AF64A through the enhancement of HACU without any side effects at the effective
      doses.

PMID- 8740081
TI  - Structure-activity relationship studies of xanthone and fluorenone-1,4
      dihydropyridine-5-phosphonates.
AB  - A series of xanthone and fluorenone-1,4-dihydropyridine derivatives bearing a 5
      phosphonate group were prepared. The compounds were evaluated for inotropic,
      chronotropic and calcium antagonistic properties. The insertion of a phosphonate
      group is detrimental for inotropic and calcium antagonistic activity but improves
      the potency and selectivity for chronotropism.

PMID- 8740082
TI  - Inhibition of lipid hydroperoxidation of low density lipoprotein by the Ca(2+)
      channel and alpha 1-adrenoceptor antagonist monatepil maleate.
AB  - The antioxidative effect of monatepil maleate (CAS 103379-03-9, AJ-2615), a new
      antihypertensive agent, was investigated by measuring its ability to inhibit
      copper-induced lipid hydroperoxidation of low density lipoprotein (LDL) and was
      compared with those of diltiazem (Ca(2+)-channel antagonist), prazosin (alpha 1
      adrenoceptor antagonist), and probucol. The concentration of AJ-2615 required to
      inhibit copper-induced lipid hydroperoxidation of LDL by 50% (IC50) was 28
      mumol/l. The IC50 values for diltiazem, prazosin, and probucol were > 1 mmol/l, >
      1 mmol/l, and 17 mumol/l, respectively. These results indicate that AJ-2615 has
      the same potent antioxidative effect as probucol and suggest that a previously
      reported ability of AJ-2615 to inhibit the progression of atherosclerosis may be
      due to this antioxidative property. In addition, the dihydrodibenzothiepine ring
      of AJ-2615 may have an antioxidative functions.

PMID- 8740083
TI  - Involvement of free radicals in the cardioprotective effect of defibrotide.
AB  - Ischemia followed by reperfusion has deleterious effects on myocardial tissue and
      a wide range of drugs have been investigated to modulate these changes.
      Defibrotide (polydeoxyribonucleotides from bovine lung), a drug with
      antithrombotic and fibrinolytic activities, has also proven to be
      cardioprotective against myocardial ischemia/reperfusion damage. However, the
      mechanism of this protective effect has not been clarified yet. The aim of this
      study was to determine whether this effect is due to protection against free
      radical induced changes. The experimental model in rabbits includes coronary
      artery ligation for 60 min followed by a reperfusion period of 45 min. In this
      model, free radical damage was estimated by different parameters of lipid
      peroxidation such as diene conjugation, carbonyl content, and thiobarbituric acid
      reactive substances, together with protein oxidation determinations. The results
      demonstrate that defibrotide prevents free radical induced changes after
      myocardial ischemia/reperfusion.

PMID- 8740084
TI  - Efficacy of topical tuaminoheptane combined with N-acetyl-cysteine in reducing
      nasal resistance. A double-blind rhinomanometric study versus xylometazoline and
      placebo.
AB  - The aim of this study was to functionally evaluate the decongestant effect of a
      topical intranasal drug (Rhinofluimucil consisting of tuaminoheptane sulphate
      (CAS 6411-75-2, THS), a vasoconstrictor, combined with N-acetyl-cysteine (CAS 616
      91-1, NAC). This was a double-blind randomized study, versus both xylometazoline
      and placebo. 18 subjects (8M and 10F, aged 20-47 years), unaffected by any
      rhinitic pathology, underwent anterior rhinomanometry. Following the basal
      evaluation (T0), subjects were randomly divided into three groups and subjected,
      in a double-blind manner, to nasal instillations (2 puffs per nostril) of THS/NAC
      (R), xylometazoline (O) and saline solution (P), respectively. Rhinomanometry was
      repeated after 5, 10 and 20 min (T5, T10, T20). Resistance and flow were measured
      in both nostrils at a pressure gradient of 150 Pa. After R and O nasal resistance
      significantly decreased from 0.30 Pa to 0.19 Pa and from 0.31 Pa to 0.17 Pa,
      respectively, and flow significantly increased; no effects were observed with
      placebo. In this study, THS/NAC showed rapid decongestant properties, with a
      significant decrease of resistance and increase of inspiratory flow. The same
      finding was observed with xylometazoline, but not with the placebo. The
      decongestant effect was rapid: it could already be observed at T5, and remained
      constant up to T20 without any rebound effect.

PMID- 8740085
TI  - Ex-vivo in-vitro inhibition of lipopolysaccharide stimulated tumor necrosis
      factor-alpha and interleukin-1 beta secretion in human whole blood by extractum
      urticae dioicae foliorum.
AB  - An extract of Urtica dioica folium (IDS 23, Rheuma-Hek), monographed positively
      for adjuvant therapy of rheumatic diseases and with known effects in partial
      inhibition of prostaglandin and leukotriene synthesis in vitro, was investigated
      with respect to effects of the extract on the lipopolysaccharide (LPS) stimulated
      secretion of proinflammatory cytokines in human whole blood of healthy
      volunteers. In the assay system used, LPS stimulated human whole blood showed a
      straight increase of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1
      beta (IL-1 beta) secretion reaching maximum concentrations within 24 h following
      a plateau and slight decrease up to 65 h, respectively. The concentrations of
      these cytokines was strongly positively correlated with the number of
      monocytes/macrophages of each volunteer. TNF-alpha and IL-1 beta concentration
      after LPS stimulation was significantly reduced by simultaneously given IDS 23 in
      a strictly dose dependent manner. At time 24 h these cytokine concentrations were
      reduced by 50.8% and 99.7%, respectively, using the highest test IDS 23 assay
      concentration of 5 mg/ml (p < 0.001). After 65 h the corresponding inhibition was
      38.9% and 99.9%, respectively (p < 0.001). On the other hand IDS 23 showed no
      inhibition but stimulated IL-6 secretion in absence of LPS alone. Simultaneously
      given LPS and IDS 23 resulted in no further increase. In contrast to described
      effects on arachidonic acid cascade in vitro, tested Urtica dioica phenol carbon
      acid derivates and flavonoides such as caffeic malic acid, caffeic acid,
      chlorogenic acid, quercetin and rutin did not influence LPS stimulated TNF-alpha,
      IL-1 beta and IL-6 secretion in tested concentrations up to 5 x 10(-5) mol/l.
      These further findings on the pharmacological mechanism of action of Urticae
      dioica folia may explain the positive effects of this extract in the treatment of
      rheumatic diseases.

PMID- 8740086
TI  - Intracellular distribution of ibuprofen within monocytes.
AB  - The interaction of ibuprofen (CAS 15687-27-1) with muscle proteins was
      investigated in vitro and binding to actin was found to be more marked than to
      other muscle proteins. Actin polymerization, however, was not influenced by this
      interaction. The kinetics of ibuprofen internalization by human
      monocytes/macrophages from peripheral blood at 37 degrees C and its partitioning
      to different cellular compartments was studied and compared to the actin content
      of these subcellular fractions. The bulk of cell-bound ibuprofen (89.7%) was
      found in the cell debris fraction (1,000 g sediment), 7.3% were recovered in the
      10,000 g sediment, only 0.5% in the 100,000 g sediment and 2.5% in the cytosolic
      fraction. The distribution of F-actin to the different subcellular fractions was
      verified by fluorescence analysis using NBD-phallacidin. Four times more F-actin
      was found in the 1,000 g sediment than in the 10,000 g fraction, while the
      microsomal fraction contained only 8% of total F-actin. In the cytosol,
      significant amounts of soluble actin were detected. These data indicate that
      ibuprofen could theoretically interact with actin in all the cellular
      subfractions to which it is distributed after internalization.

PMID- 8740087
TI  - Comparison of the anti-inflammatory effect and gastrointestinal tolerability of
      aceclofenac and diclofenac.
AB  - Aceclofenac (CAS 89796-99-6) and diclofenac (CAS 15307-79-6) are orally effective
      non-steroidal anti-inflammatory drugs. Their anti-inflammatory and potential
      gastrointestinal damaging effects were compared following single and repeated
      administration (5 days). Both drugs exerted an anti-inflammatory activity and
      showed a similar gastrointestinal tolerability in the rat.

PMID- 8740088
TI  - Pharmacological properties of quinoxaline derivatives as a new class of 5-HT3
      receptor antagonists.
AB  - The pharmacological profile of five quinoxaline derivatives, a new class of 5HT3
      receptor antagonists, is reported in the present study. All of the new compounds
      antagonized the effect of the selective 5-HT3 receptor agonist 2-methyl-5-HT in
      the isolated longitudinal muscle-myenteric plexus preparation (LMMP) of guinea
      pig ileum. One of them, VC-605) was approximately three orders of magnitude more
      potent than ondansetron. In binding studies to 5-HT3 receptors from rat cerebral
      cortex membranes only VC-605 showed an affinity comparable to ondansetron. In the
      isolated rat oesophageal tunica muscularis mucosae preparation the new compounds,
      like 2-methyl-5-HT, only produced relaxation of the contraction induced by
      carbachol at high concentrations. In vivo, the quinoxaline derivatives were weak
      antagonists of the bradycardia response to 5-HT in the anesthetized rat. The
      quinoxaline derivatives, in particular VC-501 and VC-603, prevented retches and
      vomiting induced by 2-methyl-5-HT and cis-platinum in the ferret. The new
      compounds also enhanced the gastric emptying of solids in rats. The results
      obtained are probably indicative of the suggested species- and tissue-dependent
      differences in 5-HT3 receptor subtypes. The high potency and selectivity of one
      of the new quinoxaline derivatives, VC-605, at 5-HT3 receptors of guinea-pig
      ileum is remarkable. VC-605 may be a useful tool for further characterizing this
      possible 5-HT3 receptor subtype.

PMID- 8740089
TI  - Prevention of platelet-activating factor-induced gastrointestinal lesions in rats
      by the new specific antagonist N-(2-dimethylaminoethyl)-N-(3-pyridinylmethyl)[4
      (2,4,6-triisopropylphe nyl) thiazol-2yl]amine.
AB  - SR 27417 (CAS 136468-36-5, N-(2-dimethylaminoethyl)-N-(3-pyridinylmethyl)[4
      (2,4,6-triisop ropylphenyl) thiazol-2-yl]amine), a highly potent platelet
      activating factor (PAF) receptor antagonist, was tested for its ability to
      prevent macroscopic and histologically assessed gastrointestinal (GI) lesions in
      rats induced by PAF as compared to the reference compound apafant. Both compounds
      were orally effective but SR 27417 prevented the gut lesioning effects of PAF at
      lower doses than apafant. In addition, a dose of apafant (1.5 mg/kg) that showed
      almost maximal effect when given 30 min before PAF, had lost most of its
      protective action by 3 h, while SR 27417 at a comparably effective dose (0.5
      mg/kg) retained substantial ability to prevent gut lesions in all the GI tract
      segments investigated, 18 h after administration. These findings suggest that SR
      27417 is a potent and long lasting inhibitor of PAF-induced gastrointestinal
      lesions in rats.

PMID- 8740090
TI  - Radioimmunological analysis of cyproterone acetate in human serum. Comparison
      with a gas chromatographic/mass spectrometric method and influence of each method
      on the outcome of a bioequivalence trial.
AB  - Cyproterone acetate (CAS 427-51-0, CPA) is a steroid hormone with antiandrogenic
      and progestogenic properties, which has been used in the therapy of prostate
      carcinoma in men, and for the treatment of severe acne and hirsutism in women.
      The aim of the present study was to compare two equally sensitive analytical
      methods, a radioimmunoassay (RIA) and a gas chromatographic/mass spectrometric
      method (GC/MS), for the quantitative determination of CPA in human serum samples
      and to assess their suitability for bioequivalence trials. To this end, serum
      samples which had been collected during a study on the bioequivalence oaf two CPA
      containing formulations (Androcur 100 and Androcur 50) were analysed using both
      methods. Basic pharmacokinetic parameters, like Cmax, tmax, t1/2 and AUC were
      calculated from each data set and corresponding parameters were compared by
      statistical methods. A comparison of the drug concentration-time curves obtained
      with both analytical methods revealed that in particular at later sampling times
      (48 to 120 h post dose) concentration values generated by RIA were slightly
      higher by about 20-40% than those measured with GC/MS. This indicates the
      presence of cross-reacting metabolite(s), most likely the 15 beta-hydroxy
      cyproterone acetate. Accordingly, the values of Cmax, AUC(0-120 h) and AUC were
      overestimated by the RIA method by about 10-20%, 5% and 10%, respectively.
      However, there was a high correlation between corresponding parameters derived
      from RIA and GC/MS analysis. Although AUC values were slightly overestimated with
      the RIA method was used, this had no influence on the decision about
      bioequivalence because the mean ratio of the target variables Cmax and AUC was
      not affected. The variance of the pharmacokinetic parameters which is relevant
      for the bioequivalence test were even lower for RIA based values than those
      calculated after GC/MS analysis. In conclusion, it was found that although the
      GC/MS method is superior to RIA in terms of specificity, both methods were
      equally suited to demonstrate the bioequivalence of the two CPA-containing
      formulations. Thus, in future studies of this kind, the more simple RIA may be
      used instead of GC/MS.

PMID- 8740091
TI  - Pharmacokinetics and bioavailability of tamoxifen in postmenopausal healthy
      women.
AB  - A randomised cross-over study in 24 postmenopausal women was selected to
      establish bioequivalence of two tamoxifen (CAS 10540-29-1) formulations. In
      addition, this study compiled pharmacokinetic parameters for the current 30 mg
      regimen in postmenopausal women, the target population of tamoxifen therapy. Mean
      Cmax values of 59.1 +/- 8.9 (T) and 63.6 +/0 11.1 (R) ng/ml were attained 3.6 +/-
      1.2 (T) and 3.2 +/- 1.1 (R) h after administration of 30 mg tamoxifen for the
      test (T) and the reference (R) formulation. The mean AUC (0-480) of tamoxifen was
      calculated as 3299.7 +/- 761.2 (T) and 3370.1 +/- 701.9 (R) ng x h/ml. The
      corresponding AUC (0-480) of the active metabolite, N-desmethyl-tamoxifen,
      exceeded that of the parent drug with 4359.7 +/- 830.5 (T) and 4306.3 +/- 835.2
      (R) ng x h/ml, whereas maximal concentrations of the metabolite were distinctly
      decreased with 14.4 +/- 3.3 (T) and 14.3 +/- 2.4 (R) ng/ml. The pharmacokinetic
      parameters evaluated in this study are well in line with already known
      pharmacokinetic data generated with young male volunteers and postmenopausal
      patients with breast cancer. Precise analytics and an extremely long blood
      sampling period facilitated an accurate determination of tamoxifen's half-life in
      postmenopausal women with 210.1 +/- 60.8 (T) and 209.8 +/- 59.9 (R) h. Based on
      the extremely long half-life, the suitability of a cross-over design is discussed
      and recommended for further studies.

PMID- 8740092
TI  - Application of the dynamic quantitative structure-activity relationship method
      for modeling antibacterial activity of quinolone derivatives.
AB  - The dynamic approach to quantitative structure-activity relationship (QSAR) was
      recently introduced to mimic the multiplicity of 3D-molecular shapes taken from
      the chemical at the different stages of the processes conditioning the endpoint
      under investigation. In difference with the conventional QSAR methods, where the
      structure of each compound is described by a single conformation (usually the one
      with the lowest calculated energy), the dynamic QSPR is aiming to account for the
      effects of the different solvent environments at the various reaction steps under
      which different conformations should be active. The core of the new methodology
      is the 3DGEN algorithm for an exhaustive 3D molecular design and the related
      system for an interactive conformation screening, based on the: chemical
      expertise, stereoelectronic parameter ranges and parameter distributions,
      depending on hypothesis on interaction mechanism The new methodology is
      incorporated in the OASIS (optimized approach based on structural indices set)
      computer system for QSAR/QSPR (quantitative structure activity/property
      relationship). In the present work it was applied to model in vitro (inhibition
      of Escherichia coli DNA gyrase) and in vivo (MICs against gram-negative as well
      as gram positive bacteria) antimicrobial activity (AMA) of quinolone derivatives.
      It was found that AMA is conditioned by molecular geometry as described by pair
      of topological indices and electron-acceptor properties, as assessed by the
      energies of LUMO (Lowest Unoccupied Molecular Orbital) orbitals, charges, bond
      orders and polarizability of the specific molecular sites. Interaction hypothesis
      is created, according to which polar-polar intermolecular interactions and bond
      breaking (cycle "opening", analogous to that of beta-lactam moiety in
      cephalosporins) condition biological activity. The derived QSAR models are
      significant according to the conventional statistical criteria as well as to the
      structure-activity causality requirements stated in literature. The best QSARs
      are obtained for in vitro AMA (r2 = 0.93 and s2 = 0.003), whereas for in-vivo
      activity correlations found are with lower statistics (0.54 < r2 < 0.74 and 0.005
      < s2 < 0.03). The results are statistically better than those obtained by
      Computer automated Structure Evaluation (CASE) method.

PMID- 8740093
TI  - Influence of temperature on mutational resistance to 4-quinolones.
AB  - Minimum inhibitory concentration (MIC) values of ciprofloxacin (CAS 85721-33-1),
      ofloxacin (CAS 82419-36-1) or levofloxacin (CAS 100986-85-4) against Escherichia
      coli, Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus
      epidermidis were determined at 37, 30 and 25 degrees C on nutrient agar. With E.
      coli and S. aureus, reducing the incubation temperature from 37 to 30 to 25
      degrees C decreased the MIC values for each drug. With P. aeruginosa, temperature
      reduction also decreased the MIC values for ciprofloxacin but increased the MICs
      for ofloxacin or levofloxacin. With S. epidermidis, temperature reduction
      increased the MICs for ciprofloxacin and ofloxacin but with levofloxacin the MICs
      were identical at 37 or 25 degrees C but higher at 30 degrees C. Mutants of these
      bacterial species were selected on nutrient agar containing five times their
      respective MICs of the 4-quinolones at 37, 30 and 25 degrees C. with S.
      epidermidis, temperature reduction always reduced its mutation frequency to
      resist 4-quinolones, whereas with the other three species the effect of
      temperature was more variable, and in some instances even elevated their mutation
      rates.

PMID- 8740095
TI  - Bioavailability of cefpodoxime proxetil with co-administered acetylcysteine.
AB  - In a cross-over study on twelve healthy volunteers cefpodoxime proxetil (CAS
      87239-81-4) and acetylcysteine (CAS 616-91-1) were evaluated for possible
      pharmacokinetic interactions. After a standardized breakfast, the subjects
      received p.o. either 200 mg cefpodoxime administered as cefpodoxime proxetil
      (reference) or 200 mg cefpodoxime and 200 mg acetylcysteine (test). To determine
      the pharmacokinetic profile of cefpodoxime the plasma concentrations were
      determined by HPLC. The plasma concentration-time curve of cefpodoxime was very
      similar after both regimens, and with respect to cefpodoxime bioequivalence has
      been proven. The narrow range of 90% confidence intervals for the quotient
      test/reference for Cmax and AUC indicate reliable bioavailability of cefpodoxime
      proxetil independent of co-administered acetylcysteine.

PMID- 8740094
TI  - Effect of praziquantel on serum glucose and insulin levels in normal and
      hyperglycemic rats.
AB  - The effects of praziquantel (CAS 55268-74-1) on serum glucose and insulin levels
      in normoglycemic and hyperglycemic rats were studied. Also the combined effect of
      praziquantel and glibenclamide (CAS 10238-21-8) on oral glucose tolerance in rats
      was investigated. Praziquantel, given orally in a dose of 250 mg/kg,
      significantly increased serum glucose level in hyperglycemic rats without
      changing serum insulin level. After oral glucose load, praziquantel produced a
      significant increase in serum glucose level and antagonized the hypoglycemic
      action of glibenclamide. These results indicate that praziquantel significantly
      increased serum glucose level in both hyperglycemic rats and after glucose load.
      Since insulin levels are not significantly altered by praziquantel, the
      hyperglycemic effect of this drug may be attributed to inhibition of peripheral
      glucose utilization. Care should be taken if praziquantel is prescribed to
      diabetic patients.

PMID- 8740096
TI  - Reduced neutral DNase activity in the urine of children after cytostatic therapy.
AB  - In children with cancer a reduced neutral urine DNase activity was observed at
      the end of cytostatic therapy. It is presumed that disorders in the kidney
      functions are the cause. A low neutral DNase activity is found in the blood; the
      activity is inhibited by inhibitors. The inhibitors of the enzyme are split away
      in the kidneys so that the neutral DNase activity in urine increases. Many
      cytostatic drugs can induce damage to the kidneys. This may be the reason that
      not all inhibitors of neutral DNase are split away in the kidneys and the
      activity of the neutral urine DNase is reduced at the end of cytostatic therapy.
      The process of removing the inhibitors is independent of the filtering capacity
      of the kidneys.

PMID- 8740097
TI  - In vitro susceptibility of Malassezia furfur.
AB  - Malassezia (M.) furfur is an anthropophilic fungus with complex growth
      requirements. Apart from its physiological appearance on human skin it is the
      causative agent of several skin disorders. A method for in vitro antifungal
      susceptibility testing of M. furfur in a microtiter plate assay has been
      developed. Read-out was performed colorimetrically in modified Leeming-Notman
      medium after incubation with alamarBlue. Twenty-two strains of M. furfur were
      tested, minimum inhibitory concentrations (MICs) were determined for climbazole,
      piroctone-olamine, selenium disulfide, zinc pyrithione. These substances are of
      common use in topical therapy of M. furfur-associated skin conditions. For
      climbazole, the range of MICs was between < 0.03 and 2 micrograms/ml with an
      empirical median mean of 0.03 micrograms/ml. For piroctoneolamine the range of
      MICs was between 16 and 64 micrograms/ml (mean = 64 micrograms/ml), for selenium
      disulfide between 2 and 64 micrograms/ml (mean = 8 micrograms/ml), and for zinc
      pyrithione between 0.12 and 8 micrograms/ml (mean = 1 micrograms/ml). These data
      indicate the high in vitro activity of climbazole against M. furfur, followed by
      zinc pyrithione. Selenium disulfide and piroctone-olamine were less active.

PMID- 8740098
TI  - Clinical and pharmacokinetic evaluation of a new lipid-based delivery system of
      amphotericin B in AIDS patients.
AB  - To evaluate the safety, tolerance and pharmacokinetics of a new formulation of
      amphotericin B (AmB; CAS 1397-89-3) 18 AIDS patients treated for different kinds
      of mycoses were studied: oropharingeal and/or esophageal azole-resistant
      candidiasis (9), CNS cryptococcosis (7) or aspergillosis (2). Amphotericin B
      daily dose was infused in 100 ml of a lipid emulsion. The patients aged from 26
      to 54 years with body weight ranging from 42 to 89 kg. Blood samples were
      collected at fixed intervals and plasma stored at -20 degrees C until tested by a
      specific HPLC assay. The individual kinetic analysis of plasma drug levels was
      performed by a two-compartment open model. The data were analyzed using P-Pharm,
      a computer program designed for population pharmacokinetic analysis that allows
      pooling of data. The effect of a variety of demographic factors on clearance and
      volume of distribution was investigated. The clearance and the apparent volume of
      distribution were, respectively, (mean +/- SD): 0.037 +/- 0.015 l/h/kg and 0.45
      +/- 0.32 l/kg. The interindividual variability in AmB clearance and volume of
      distribution was modelled with proportional error with an estimated coefficient
      of variation of 40.6% and 70.9%, respectively. Clinical and biological tolerance
      was very good and no patient experience infusion-related adverse effects or
      hematologic and hepatic toxicity; a moderate renal failure occurred in only one
      patient.

PMID- 8740099
TI  - Wound healing effect of malotilate in rats.
AB  - The wound healing effect of malotilate (CAS 59937-28-9, NKK-105) was investigated
      by using an excisional skin-wound model produced on the back of normal and
      healing-impaired (induced by prednisolone pretreatment) rats. The rapid decrease
      in the square measure of wound areas and the improvement in the histological
      evaluation clarified that 0.3% and 1% cream preparations of malotilate were
      obviously effective in accelerating spontaneous healing in the normal rats. The
      accelerative effect of malotilate cream preparations was likely superior to that
      of an ointment containing 5% deproteinized calf blood extract used as a reference
      agent. The same effect was also observed in the healing-impaired rats. The
      histological findings revealed that a thicker and more cellular granulation
      tissue, which in turn created an adequate bed for rapid re-epithelization, was
      formed in the malotilate-treated animals. Acceleration of granulation tissue
      formation by malotilate was also supported by the cotton pellet implantation
      method. It is concluded from these results that malotilate seems to be a
      promising agent for topical wound therapy.

PMID- 8740100
TI  - Secretory non-pancreatic phopholipase A2 in severe sepsis: relation to endotoxin,
      cytokines and thromboxane B2.
AB  - Circulatory secretory non-pancreatic phospholipase A2 (snp-PLA2) was measured
      prospectively at the onset (day 0) of severe sepsis in 52 patients as well as on
      day 1 and 2 in 25 patients, in order to answer two questions: 1) does the snp
      PLA2 plasma concentration differ according to the type and severity of infection?
      2) what is the relation between snp-PLA2 and other mediators involved in severe
      sepsis, such as endotoxin, cytokines (TNF alpha, IL-1 beta, IL-6) and thromboxane
      B2 (the stable metabolite of thromboxane A2)? On day 0, the snp-PLA2 circulatory
      level was 78 +/- 17 nmol/min/ml in patients with severe sepsis as compared to 3.5
      +/- 2 nmol/min/ml in 40 healthy volunteers. There was no statistical difference
      according to the outcome, the presence of shock, or the type of infection on day
      0. However, snp-PLA2 remained elevated or even increased in patients who
      ultimately died, while it decreased in survivors (p = 0.01 by ANOVA). The
      cytokine profiles during the 2-day follow-up were similar to that of snp-PLA2,
      but the differences were not statistically significant between survivors and non
      survivors. No correlation was found between snp-PLA2 and other mediators for
      either initial or peak values.

PMID- 8740101
TI  - Chlamydia pneumoniae community-acquired pneumonia: a review of 62 hospitalized
      adult patients.
AB  - In a prospective study, Chlamydia pneumoniae was identified as the etiological
      agent in 62 (17.9%) of 346 adult patients hospitalized over the course of one
      year for community-acquired pneumonia at the Soroka Medical Center in Beer-Sheva,
      Israel. The diagnosis of C. pneumoniae infection was based on serological testing
      of antibodies by the MIF technique. In 43 of these patients (69.4%), at least one
      other etiological agent, in addition to C. pneumoniae for community-acquired
      pneumonia was identified. Streptococcus pneumoniae was identified in 34 patients
      with C. pneumoniae (54.8%), as an additional causative factor in infection.
      Community-acquired pneumonia patients with C. pneumoniae were significantly older
      than non-C. pneumoniae patients (p = 0.03), had a higher APACHE II score on
      admission (p < 0.05), a higher rate of positive blood cultures (p = 0.02), and
      longer periods of hospitalization (p = 0.022). Seven patients with pure C.
      pneumoniae infection recovered, despite treatment which is not considered to be
      specific for C. pneumoniae. It was concluded that C. pneumoniae is a common
      etiological agent for community-acquired pneumonia in our region, particularly in
      the elderly, and is characterized by a high rate of concomitant infections with
      other pulmonary pathogens. No specific clinical or radiological pattern was
      discerned that could distinguish between C. pneumoniae community-acquired
      pneumonia and non-C. pneumoniae community-acquired pneumonia.

PMID- 8740102
TI  - Diminished T lymphocyte proliferative response to polyclonal mitogens in acute
      brucellosis patients.
AB  - T lymphocytes from 21 untreated patients with acute brucellosis were tested for
      their proliferative response to polyclonal mitogens. The purified T lymphocytes
      from these patients showed a defective proliferative response to plant lectins
      and anti CD3 monoclonal antibodies with respect to the response observed in T
      lymphocytes from 21 healthy controls (p < 0.05). This defective proliferative
      response was not corrected by the exogenous addition of interleukin-2 or tumor
      necrosis factors alpha or beta to the culture medium. After antibiotic therapy,
      the proliferative response to the mitogens in T lymphocytes was found to be
      similar to that of the healthy controls (p > 0.05), and significantly higher than
      that found before treatment (p < 0.05). It was concluded that T lymphocytes from
      acute brucellosis patients have a defective proliferative response to membrane
      mitogenic signals, which disappears when the patients are cured after antibiotic
      treatment.

PMID- 8740103
TI  - Foscarnet 5 versus 7 days a week treatment for severe gastrointestinal CMV
      disease in HIV-infected patients.
AB  - In a randomized open trial foscarnet 90 mg/kg b.i.d. 5 days for 3 weeks was
      compared to 90 mg/kg b.i.d. daily in severe gastrointestinal cytomegalovirus
      disease in HIV-infected patients. Thirty-eight patients were randomized, 36 were
      evaluable (all male, age 24-54 years, median 40 years; CD4/microliter 0-150,
      median 10). Treatment efficacy was evaluated based on a score consisting of
      symptoms, endoscopic and histologic examination. In the 5-day treatment group
      10/16 (62%) patients responded to treatment, in the 7-day treatment group 13/20
      (65%), with symptoms resolving in most patients after 1 week. Side effects and
      adverse events were seen in 13 patients in the 5-day treatment group and in 15
      patients in the 7-day treatment group. Laboratory abnormalities were common in
      both groups, in one patient reversible renal insufficiency developed. Efficacy
      and safety of treatment 5 days a week was comparable to the standard regimen.

PMID- 8740104
TI  - Increased cerebrospinal fluid levels of glial fibrillary acidic protein (GFAp) in
      Lyme neuroborreliosis.
AB  - Glial fibrillary acidic protein (GFAp), the main protein constituent of the
      intermediate filaments of astrocytes, was analysed in the cerebrospinal fluid
      (CSF) of 20 patients with Lyme neuroborreliosis as a marker of the astroglial
      reaction. The mean GFAp level before antibiotic treatment in the study group was
      significantly elevated (592 pg/ml +/- 596 [SD]) compared to that in 24 healthy
      controls (121 +/- 87 [SD]) (p < 0.01). The highest CSF-GFAp levels were seen in
      the patients with the most severe disease, but the levels were also increased in
      patients with peripheral paresis, such as facial palsy with no or only minor
      encephalitic symptoms. This implies that the infection was not limited to radix
      dorsalis or the meningeal tissues, but affected the central nervous system as
      well. Furthermore, the astroglial reaction seemed to occur early in Lyme
      neuroborreliosis since CSF-GFAp levels were elevated also in patients with recent
      (< 3 weeks) onset of disease. After antibiotic treatment, the GFAp levels
      decreased. It is suggested the CSF-GFAp concentrations might be useful for
      monitoring CNS involvement in Lyme neuroborreliosis.

PMID- 8740105
TI  - Management of herpes simplex virus type 1 pneumonia following liver
      transplantation.
AB  - Interstitial pneumonia caused by Herpes simplex virus type 1 (HSV-1) is a severe
      complication of orthotopic liver transplantation (LTX). The records of patients
      were reviewed who had an LTX at the age of 16 years or older between 1991 and
      1994 with a mean follow-up of 21 months (range, 10 to 44 months). Six patients
      were included who had fever of > 38 degrees C, deterioration of arterial blood
      gases, radiological evidence of interstitial pneumonia and proof of HSV-1 in
      bronchoalveolar lavage fluid. All patients were anti-HSV-IgG positive before LTX.
      All patients were successfully treated with intravenous acyclovir, mechanical
      ventilation and reduced immunosuppression. Three patients who received
      cyclosporin A had a rejection which was successfully treated by switching to FK
      506. Four patients were discharged in good health. One patient died 36 months
      after LTX of an unrelated cause. One patient died of urosepsis on postoperative
      day 139. Acyclovir together with mechanical ventilation and reduced
      immunosuppression proved to be an effective treatment for HSV-1 pneumonia
      following LTX.

PMID- 8740106
TI  - Randomized comparison of two nystatin oral gels with miconazole oral gel for
      treatment of oral thrush in infants. Antimycotics Study Group.
AB  - Recently, two commercial oral nystatin gels have been marketed in Germany (Candio
      Hermal, Hermal; Lederlind, Lederle). In a prospective open randomized multicentre
      study involving 12 paediatricians in private practice, Candio-Hermal and
      Lederlind were compared with miconazole oral gel (Daktar, Janssen) in 95 infants
      with oral thrush (candidosis). Oral and rectal swabs were taken on days 0 and 14.
      Treatment duration varied according to the amount of drug contained in one tube
      (Candio-Hermal 10 days; Lederlind 14 days; Daktar 8 days). On day 14, clinical
      cure was observed in 23 of 27 infants treated with Daktar (85.1%), in 15 of 35
      infants treated with Candio-Hermal (42.8%; p < 0.0007); and in 16 of 33 infants
      treated with Lederlind (48.5%; p < 0.004). Clinical relapses were observed in 15
      patients (Candio-Hermal: n = 9; Lederlind: n = 6). The overall oral mycologic
      cure rate was significantly higher with Daktar (29.6%) and Candio-Hermal (20.0%)
      than with Lederlind (3.0%; p < 0.005 and < 0.03, respectively). It can be
      concluded that Daktar oral gel is significantly more effective than Candio-Hermal
      and Lederlind in curing oral thrush in infants.

PMID- 8740107
TI  - Evaluation of the Amplicor HCV test: experiences after 1 year of routine use in a
      diagnostic laboratory.
AB  - To evaluate the usefulness of a standardized commercial amplification assay for
      detection of hepatitis C virus (HCV) RNA, Amplicor HCV Test (Roche), a total of
      1,204 serum samples from 888 patients was examined. Seven out of 443 anti-HCV
      negative samples, 638 out of 729 anti-HCV-positive samples and four out of 32
      anti-HCV-indeterminate samples tested HCV RNA positive by Amplicor in initial
      testing. One false-negative and five false-positive Amplicor results were found
      in initial testing, giving an overall sensitivity and specificity of the Amplicor
      HCV Test of 99.8% and 99.1%, respectively. Our study confirmed that the Amplicor
      HCV Test is a practical, rapid, sensitive and specific assay for detection of HCV
      RNA. However, the results must be interpreted with some caution and with the
      patient's anti-HCV status and clinical data in mind.

PMID- 8740108
TI  - Etiological agents and predisposing factors of intracranial abscesses in a Greek
      university hospital.
AB  - The bacteriology for 21 patients with brain abscesses is presented and correlated
      with their predisposing conditions. Chronic otomastoiditis was the most common
      predisposing factor, and the overall most frequent infected sites were the
      frontal and temporal regions. Gram-negative non-sporeforming anaerobes of the
      genus Bacteroides and Fusobacterlum followed by aerobic streptococci were the
      predominant pathogens. Enterobacteria were only identified in postcraniotomy
      abscesses, while a substantial number of fastidious species was detected in
      suppurations related to congenital heart disease. Altogether, anaerobes alone
      were recovered in seven patients, aerobes alone in six, and mixed aerobes and
      anaerobes in four patients. These findings confirm the predominant role of
      anaerobes in the etiology of intracranial suppurations.

PMID- 8740109
TI  - Prevalence of hepatitis A antibodies in food handlers in Italy.
AB  - The aim of the study was to investigate the anti-HAV prevalence in food handlers
      in the area of Catanzaro, Italy. A cross-sectional survey was performed by
      selecting all food handlers attending local health units for routine medical
      examination during the period from May 1994 through December 1994. A prevalence
      of 68.7% was recorded in the 294 participating subjects, and it increased
      significantly with increasing age (Chi-square test for trend = 126.95; p <
      0.0001). Multiple logistic regression analysis showed a significant association
      in the prevalence of anti-HAV with years of activity: food handlers with ten or
      more years' experience have an adjusted odd ratio of 2.4 (95% CI = 1.01-5.6)
      compared to those with a shorter period of activity. The results indicate that
      finding and implementing ways to motivate food handlers to use correct infection
      control measures routinely should be made a priority.

PMID- 8740110
TI  - The effects of ciprofloxacin on human chondrocytes in cell culture.
AB  - Ciprofloxacin is a highly potent antibacterial agent that is used extensively in
      bone and joint infections. Because of reports of potential chondro-toxicity in
      animals, the effects of this drug on cells derived from human cartilage were
      tested in liquid micromass and agarose gel cultures. An inhibition of cell
      proliferation as indicated by a decrease in [3H]-thymidine uptake and
      bromodeoxyuridine labeling at ciprofloxacin concentrations of 0.5 and 50 mg/l was
      found which corresponded to the therapeutic and toxic serum levels. There was no
      effect on proteoglycan synthesis as indicated by 35SO4 incorporation.
      Immunocytochemistry showed no changes in morphology or staining patterns for type
      I procollagen, type-II collagen, keratan sulfate and unsulfated chondroitin.
      Because the amount of inhibition of DNA synthesis varied with different
      ciprofloxacin concentrations, this data suggests that this agent has a
      differential effect on newly differentiating cells and might be the basis for
      contraindication in pediatric patients.

PMID- 8740111
TI  - Antibody response to measles vaccination in Turkish children.
AB  - In recent years, there has been a remarkable increase in measles cases among
      preschool and secondary school children in Turkey, as in many other countries.
      The seroconversion and coverage rates of measles vaccine should therefore be
      evaluated in order to obtain data that could be used to determine the vaccination
      policy for Turkey. Measles immunity status was studied by an enzyme-linked
      immunosorbent (ELISA) test determining the anti-measles IgG antibody levels.
      Measles specific IgG antibodies were found to be positive in 77.88% of the entire
      study group of 800 children aged 11 months to 12 years, while 21.25% had negative
      sera. Seven (0.87%) subjects had borderline results. The results of this study
      indicate the need to administer a second dose of measles vaccine, preferably at
      18 months of age concomitant with other vaccines. This vaccination policy,
      together with an increase in the extent of immunization coverage, may help to
      achieve the World Health Organization's (WHO) target of the complete eradication
      of measles.

PMID- 8740112
TI  - Polyarteritis nodosa and HIV infection: no evidence of a direct pathogenic role
      of HIV.
AB  - A case of polyarteritis nodosa identified by the American College of Rheumatology
      (ACR) 1990 criteria in a 44-year-old HIV-infected man is described. The search
      for cytomegalovirus, HBV and B19 parvovirus infections was negative. In situ
      hybridization did not reveal proviral HIV-1 DNA in a skin sample. A zidovudine
      associated vasculitis was excluded. Corticosteroid therapy resolved vasculitis
      manifestations and was well tolerated without opportunistic infections during the
      10-month follow-up period. An indirect pathogenetic role of HIV as a possible
      cause of vascular damage cannot be excluded in our patient.

PMID- 8740113
TI  - Sepsis syndrome induced by tuberculous perforation of the esophagus.
AB  - Perforation of the esophagus induced by tuberculosis with no evidence of HIV
      infection is an extremely unusual presentation of the disease. We report on a 41
      year-old man presenting with an esophageal perforation who developed a sepsis
      syndrome characterized by multiple organ dysfunction. The perforation was covered
      endoscopically with a tube, the patient recovered from cardiovascular, renal and
      pulmonary dysfunction under intensive care treatment, including antimycobacterial
      therapy. In response to endoscopic and medical treatment the size of the lesion
      decreased and disappeared 56 days after diagnosis. The patient could be
      discharged 2 months after admission and remained asymptomatic after a 12 month
      follow-up examination.

PMID- 8740115
TI  - Boostering antitoxic diphtheria immunity in adults.

PMID- 8740114
TI  - Streptococcal toxic shock syndrome in a postpartum woman. Case report and review
      of the literature.
AB  - A case of streptococcal toxic shock syndrome in a 29-year-old postpartum woman is
      described. The patient presented with hypotension, coagulation defects, adult
      respiratory distress syndrome and scarlet exanthema as a complication of
      hemolytic group A streptococcal endometritis. One hundred and twenty-two other
      cases of streptococcal toxic shock syndrome in the literature are reviewed and
      the criteria of the syndrome discussed. Streptococcal toxic shock syndrome seems
      to be increasing along with more frequent invasive streptococcal infections in
      several countries. It is therefore important to recognize and treat the infection
      as early as possible to minimize the risk of mortality.

PMID- 8740116
TI  - Therapy of Lyme borreliosis in children.
AB  - A retrospective open study was conducted to determine the efficacy of penicillin
      and ceftriaxone in children with skin manifestations of Lyme borreliosis
      (solitary erythema migrans, multiple erythemata, borrelial lymphocytoma) and
      neuroborreliosis, respectively. One hundred sixty children were treated with
      penicillin and 41 with ceftriaxone for an average of 12 days. Serum antibodies to
      borreliae were determined before therapy and 2-3 and 4-6 weeks thereafter. At
      admission 44%/26%,8%/42%, and 40%/35% of erythema migrans, borrelial lymphocytoma
      and neuroborreliosis patients, respectively, were IgM/IgG positive. Four to 6
      weeks after treatment the percentage of seropositives was 20%/15%,8%/61%, and
      21%/44%, respectively. A 3 months follow-up was completed with 151 children. No
      child showed clinical evidence of illness, nor were there abnormalities in
      laboratory parameters.

PMID- 8740117
TI  - beta-lactam antibiotics in the treatment of neuroborreliosis in children:
      preliminary results.
AB  - In vitro beta-lactam antibiotics like ceftriaxone and penicillin G sodium have
      been shown to be active against Borrelia burgdorferi. Results of quantitative
      determinations of both antibiotic substances in the CSF for children are limited.
      Seventy-five children (median age 96 months, range 10 to 176 months) with
      probable or definite neuroborreliosis were treated with ceftriaxone (1 x 50-90
      mg/kg/day) or penicillin G sodium (4 x 80,000-120,000 IU/kg/day) intravenously.
      On day 10 of therapy levels of penicillin G sodium (1,1.5,2,3,4, 5, or 6 h after
      i.v. administration), and ceftriaxone (1,2,4,6,12 or 24 h after i.v.
      administration) in serum and CSF were measured with a micro agar diffusion
      bioassay. Results demonstrate that after 5 h penicillin G sodium in CSF was above
      the minimal inhibitory concentration (MIC) but after 6 h penicillin G sodium
      levels were below the determination limit in 60% of the cases. All ceftriaxone
      results in CSF-even after 24 h-were above MIC. Penicillin G sodium serum values
      ranged from 46.6 to 0.1 mg/L (1 to 6 h post dose) and ceftriaxone serum values
      from 261 to 5 mg/l (1 to 24 h post dose). The role of penicillin G sodium and
      ceftriaxone and administration intervals of both antibiotics in the therapy of
      neuroborreliosis in children are discussed.

PMID- 8740118
TI  - Controversies in the use of antimicrobials for the prevention and treatment of
      Lyme disease.
AB  - Unanswered questions in the management of patients with Lyme disease or those who
      have had Ixodes tick bites include: Is antimicrobial therapy effective in
      preventing Lyme disease during the incubation period of the infection? Which oral
      agents are most effective in treatment of Lyme disease? Are macrolides
      efficacious? And, for how long a time period should antimicrobial therapy be
      given? Potentially useful insights into these questions can be gained by
      examining experience with other spirochetal infections. Using this information,
      in conjunction with existing data from recent studies on Lyme borreliosis,
      tentative answers to these questions can be formulated. Based on this analysis,
      it would be anticipated that a short course of antibiotic therapy, perhaps even a
      single dose, will be effective in preventing Lyme disease after a tick bite. Beta
      lactam antibiotics such as amoxicillin, and tetracycline preparations, such as
      doxycycline, are the mainstays of oral therapy for treatment of active infection.
      Macrolides are less effective, but their utility is likely to be improved if they
      are given in maximal dosage. There is no convincing evidence for extending
      treatment of early Lyme disease beyond 14 days. There is also no evidence that
      longer therapy is more efficacious for other manifestations of Lyme disease,
      although this issue deserves further study.

PMID- 8740119
TI  - Physician preferences in the diagnosis and treatment of Lyme disease in the
      United States.
AB  - To assess physician preferences in the diagnosis and treatment of Lyme disease,
      questionnaires were sent to physicians in various Lyme disease endemic areas in
      the U.S. Seventy-eight responses were analyzed. Both ELISA and Western blot were
      ordered by 86% of responders. Fifty percent of responders believed that 25% or
      more of patients who have Lyme disease were seronegative. The treatment was
      influenced by physician specialty. Antibiotic treatment for tick bite was
      prescribed by 20% of responders. Erythema migrans rash was treated by all
      responders without serologic confirmation. The median treatment duration of
      erythema migrans was 4 weeks. For post-erythema migrans Lyme disease, 43% of
      responders treat 3 months or more; for chronic Lyme disease, 57% of responders
      treat 3 months or more. Our survey documents significant differences between
      published recommendations and actual practices. Physician education and clinical
      trials are needed to clarify the reasons for these differences.

PMID- 8740120
TI  - Prevention of borreliosis in persons bitten by infected ticks.
AB  - A study on prevention of borreliosis in humans bitten by infected ticks was
      performed in 1992-1994 in the Perm' region of Russia. Adult Ixodes persulcatus
      ticks were removed from the study subjects, and live preparations made from the
      material obtained from the gut of each tick were microscopically analyzed (up to
      250 microscopic fields per preparation). Persons were divided into experimental
      and control groups (261 and 97 persons, respectively). The experimental group
      received doxycycline (100 mg twice daily) for 3-5 days after the tick bite. In
      the control (untreated) group, 12 persons contracted borreliosis. In the
      experimental group, the disease was diagnosed in three subjects. Morbidity per
      100 patients in the experimental group was 1.1, i.e. 11 times lower than that in
      the control group. Identification of Borrelia in ticks by microscopic analysis,
      followed by a short-term treatment with antibiotics according to microbiological
      indications, is an efficient method for preventing persons from contracting
      borreliosis.

PMID- 8740121
TI  - The outer surface protein A (OspA) of Borrelia burgdorferi: a vaccine candidate
      and bioactive mediator.
AB  - In the search for a suitable vaccine candidate for Lyme borreliosis the
      principles of protective immunity were studied in a murine model of Borrelia
      burgdorferi infection. It was found that the spirochetal outer surface protein A
      (lipOspA) in its native and recombinant lipidated form induces monospecific
      immune sera, which in passive transfer experiments protect SCID mice against
      experimental and tick-borne infection and disease. These and similar findings of
      independent groups led to the development of a vaccine formulation containing
      lipOspA. When tested in clinical phase I/II safety trials the recombinant lipOspA
      vaccine was shown to be safe, immunogenic and able to elicit borreliacidal
      antibodies. At present, clinical phase III efficacy trials are being conducted.
      B. burgdorferi infection involves the dissemination of the spirochetes from the
      site of the tick bite, infection of distant organs, and induction of a chronic
      inflammatory process. Recent studies indicate that the spirochetes may utilize
      host-derived enzyme systems to increase their virulence/pathogenicity. It was
      found that lipOspA serves as a surface receptor for the host-derived proteolytic
      enzyme plasmin(ogen), the central component of the so-called plasminogen
      activator system. Moreover, it was found that spirochetes are able to activate
      endothelial cells and blood-derived leukocytes, such as monocytes/macrophages, B
      cells and T cells, to express functions and/or secrete molecules, which are known
      to promote inflammatory responses. Part of these activities were exerted by the
      isolated lipOspA. The studies indicate an important role of lipOspA, both for the
      induction of a protective immune response by the host, as well as for the
      pathogenic processes elicited during B. burgdorferi infection.

PMID- 8740122
TI  - Experimental immunization against Lyme borreliosis with recombinant Osp proteins:
      an overview.
AB  - Interest in human and veterinary vaccines against Lyme borreliosis is growing.
      Both whole cell immunization and subunit vaccines can protect against infection
      with Borrelia burgdorferi. For development of a human vaccine the focus has been
      on a subunit vaccine. The most promising candidate is OspA, a major outer
      membrane lipoprotein of B. burgdorferi sensu lato. Of Osp proteins A through D,
      OspA shows the least variability between strains in its sequence and in the level
      of its expression. Borreliae in ticks express OspA. Antibodies to OspA kill
      borreliae in vitro and provide passive protection in mice. Active immunization of
      mice with OspA provides protection against challenge by syringe inoculation or
      tick bite. The lipid moiety of the OspA is necessary for immunogenicity in the
      absence of a potent adjuvant. A recombinant OspA-based vaccine is already in
      clinical trials. Although there is compelling evidence that immunization with
      OspA will provide protection, questions remain regarding the duration of
      protection from such immunization, the necessity to have a minimum level of
      neutralizing antibodies at all times for protection, and the relationship of an
      immune response to OspA and autoimmune features of Lyme borreliosis. The
      experimental aspects of immunization with Osp-A based constructs and other Lyme
      vaccine candidates are reviewed and discussed.

PMID- 8740123
TI  - Lyme disease vaccine.
AB  - Subunit vaccines consisting of single recombinant outer surface proteins (Osp) of
      Borrelia burgdorferi have been highly successful in protecting mice against
      challenge by borrelial strains closely related to the strain from which the
      immunogen was derived. Humoral immunity is sufficient for protection. A dual mode
      of action for these vaccines has been suggested because serum factors ingested by
      the tick during the blood meal may begin to reduce the spirochete inoculum prior
      to transmission to the host. At present two different recombinant OspA vaccine
      preparations (monovalent) are being evaluated in humans in large-scale phase III
      efficacy trials in the United States. Local discomfort at the intramuscular
      injection site has been the principal adverse effect seen to date with these
      vaccines, but further data on safety are being collected. The greater
      heterogeneity of OspA among Lyme Borrelia in Europe implies that a vaccine
      preparation containing multiple antigens (multivalent) may be necessary there,
      although this is also a concern in the United States.

PMID- 8740124
TI  - Immunological and molecular variability of OspA and OspC. Implications for
      Borrelia vaccine development.
AB  - Borrelia burgdorferi sensu lato, the etiological agent of Lyme borreliosis is
      considerably heterogeneous in Europe. Since the outer surface proteins OspA and
      OspC are the most promising candidates for a Borrelia vaccine the immunological
      heterogeneity of these proteins was investigated. By immunological analysis with
      monoclonal antibodies and sequence analysis of PCR amplified OspA and OspC at
      least seven and 16 different types, respectively, were found. Whereas skin
      isolates (n = 68) were quite homogeneous (84% belonged to OspA-serotype 2 or
      Borrelia afzelii), isolates from human cerebrospinal fluid and from ticks (n = 43
      and n = 90 respectively) were highly heterogeneous in their OspA-serotypes with
      prevalence of the Borrelia garinii associated types (about 70%). OspA-type 4 was
      often found among isolates from cerebrospinal fluid (28%). In ticks type 4 OspA
      has not been detected by culture so far. However, as reported in a previous
      study, type 4 OspA could be detected in ticks by the highly sensitive PCR
      technique.

PMID- 8740125
TI  - Management of the isolated congenital tracheo-oesophageal fistula.
AB  - Over a ten-year period sixteen infants with isolated congenital tracheo
      oesophageal fistulas (TOF) were treated. All infants were symptomatic from birth
      although the diagnosis was only established in the neonatal period in eleven
      cases. Tube oesophagography was the diagnostic investigation of choice.
      Bronchoscopic cannulation of the fistula greatly assisted division, which was
      achieved through a cervical incision in all cases. There were two early recurrent
      fistulas both of which closed spontaneously. Persistent oesophageal symptoms were
      common. Seven of the patients (43%) experienced dysphagia, three of whom
      developed oesophageal strictures requiring repeated dilation.

PMID- 8740126
TI  - Is there any predictive characteristic for malignancy in thyroid enlargements
      during childhood?
AB  - Although thyroid surgery is mainly based on the malignancy risk, determination of
      cases with thyroid malignancy among the patients with enlarged thyroid is a
      controversial issue in children. To find out whether thyroid enlargements have
      any predictive clinical or laboratory characteristic for thyroid malignancy, a
      retrospective clinical study was scheduled. A total of 137 patients who had
      undergone surgery for thyroid enlargement in a 15-year period were evaluated. The
      series was composed of 90 (65.7%) cases with uninodular goiter, 40 (29.2%) cases
      with multinodular goiter and seven (5.1%) cases with diffuse goiter.
      Histopathologic examination showed nine (6.6%) patients with differentiated
      thyroid carcinoma. All the remaining patients had benign thyroid enlargements.
      Analysis of results showed no ideal or near-ideal predictive one for thyroid
      malignancies among clinical or laboratory characteristics consisting of age, sex,
      presumptive symptoms, previous irradiation, type of nodularity, nodule
      localization and size, lymphadenopathy, thyroid function tests, ultrasonography
      and thyroid scan. No characteristic studied had a simultaneous high level of
      positive and negative predictive value. Only two physical characteristics
      including nodule size less than 2.5 cm in diameter and lymphadenopathy had
      simultaneous high levels of sensitivity and specificity above 50%. Therefore new
      guidelines with higher predictivity should be sought for surgical evaluation of
      the childhood thyroid enlargements. Fine-needle aspiration biopsy that is
      extensively used in adults may also be an alternative approach despite some
      restrictive aspects in children.

PMID- 8740127
TI  - Duodenal atresia: a comparison of three modes of treatment.
AB  - To determine the most successful mode of treatment, 33 consecutive cases of
      duodenal atresia treated by duodenoduodenostomy and not associated with other
      gastro-intestinal anomalies were analysed retrospectively. These patients have
      been placed in a nonrandomised fashion into one of three groups: Group A:
      Duodenostomy (side to side) with gastrostomy and transanastomotic feeding tube (n
      = 12); Group B: Duodenoduodenostomy (diamond shape) with jejunostomy feeding tube
      (n = 12); Group C: Duodenoduodenostomy (diamond shape) only (n = 9). A
      nasogastric tube was used in all cases. There was no difference between the
      groups for gestational age, birthweight, and age at operation. The outcome
      measures used to compare these groups were the time taken to achieve full
      preanastomotic feeds and the duration of hospital stay. There was no difference
      in time taken to achieve full pre-anastomotic feeds between Group A and Group B.
      Patients in Group C took significantly less time to achieve full pre-anastomotic
      feeds than either of the other two groups (p < 0.05, Mann-Whitney U). The
      duration of hospital stay was also significantly shorter for patients in Group C
      (median = 12 days) than for patients in either Group A or B (median = 24, 20 days
      respectively) (p < 0.05, Mann-Whitney U).

PMID- 8740128
TI  - Choledochal cyst: varied clinical presentations and long-term results of surgery.
AB  - The clinical features and long-term outcome of 21 children with choledochal cyst
      treated over a 31-year-period is reviewed. All 7 infants ( < 1-year-old)
      presented with jaundice. Only 3 older children (14%) presented with the classical
      triad of pain, jaundice and an abdominal mass. Other forms of presentation
      included pancreatitis (n = 8), cholangitis (n = 3), biliary peritonitis (n = 2)
      and biliary cirrhosis (n = 2). An incidental diagnosis of a choledochal cyst was
      made in 3 patients one each with bilateral ureteroceles, renal hypoplasia and
      meningitis with hepatitis A infection. An elevated serum amylase (SA: mean = 1005
      U/L) and intraoperative bile amylase (BA: mean = 16,902 U/L) was observed in all
      8 children with pancreatitis. Complete excision of the choledochal cyst with Roux
      en-Y hepaticojejunostomy was the primary operative procedure in 18 patients. The
      remaining patients underwent cystoduodenostomy (n = 2) and cystojejunostomy (n =
      1). Recurrent cholangitis and stricture formation complicated cyst enterostomies.
      In comparison cyst excision with Roux-en-Y hepaticojejunostomy gave excellent
      long-term results with minimal complication.

PMID- 8740129
TI  - Role of initial near total (95%) pancreatectomy in persistent neonatal
      hyperinsulinism (PNH).
AB  - A retrospective analysis of data on all infants with persistent neonatal
      hyperinsulinism (PNH) in our hospital during a nine-year period (July 1983 to
      June 1992) was carried out. The extent of pancreatectomy and outcome based on
      long-term follow-up were reviewed. Fourteen of the 18 cases, diagnosed at our
      facility according to the established criteria of PNH, underwent surgery. Two
      patients who were managed medically because of milder disease and reluctance of
      parents for surgery and two patients who were diagnosed and operated upon outside
      our facility were excluded from this study. One patient, operated upon in 1985,
      needed re-surgery after 95% pancreatectomy because of recurrent hypoglycaemia
      unresponsive to medical treatment. This case influenced our management in a
      subsequent patient in whom we performed total pancreatectomy as an initial
      procedure. Both these patients are still diabetic. Three more patients had
      recurrence of hypoglycaemia after 95% pancreatectomy, two were managed
      successfully with a short course of diazoxide, the third had associated carnitine
      deficiency and his hypoglycaemia resolved after a short period of carnitine
      therapy. The first patient in our series had 85% pancreatectomy, the other 11
      patients had 95% pancreatectomy as an initial procedure. The 12 patients are
      normoglycaemic and off all medication. We conclude that 95% pancreatectomy as an
      initial procedure for PNH offers the best prognosis and that recurrence of
      hypoglycaemia does occur following 95% pancreatectomy and can easily be managed
      medically.

PMID- 8740130
TI  - Traumatic and non-traumatic pancreatitis in pediatric surgery.
AB  - Today pancreatitis is classified only as acute or chronic. In pediatric surgery
      it seems more practical to distinguish traumatic from non-traumatic cases. To
      show whether there is also a difference in the management of these two groups we
      analysed all patients treated between 1977 and 1991 for pancreatitis. It was most
      impressive that traumatic cases were operated on in 86% and the rate of
      pseudocysts reached 61.5% whereas non-traumatic pancreatitis required surgical
      intervention in 50% and developed pseudocysts in 17%. Following trauma elevation
      of serum enzyme concentration lasted longer in a significant number of patients
      but became normal without any hint of further complications. In non-traumatic
      pancreatitis it is recommended that surgery should be avoided and reserved for
      complications. Exceptions are obstructions of the pancreaticobiliary ducts which
      need early removal to prevent chronicity of the disease and functional loss of
      the organ.

PMID- 8740131
TI  - Necrotizing enterocolitis: late surgical results after enterostomy without
      resection.
AB  - Between January 1985 and December 1992, 36 neonates were treated for necrotizing
      enterocolitis (NEC). 13/36 were treated conservatively and 2 (18%) died. 23/36
      required surgical treatment at birth and 6/23 (26%) died; 14, out of 17 surviving
      initial surgery, underwent reintervention to restore intestinal continuity, 3 to
      26 months later. In these 14 infants the acute necrotizing process involved the
      whole colon and ileum in 3 cases, the whole colon in 5, part of the colon in 3,
      part of the colon and ileum in 2 and was confined to the ileum in 1. 11 cases
      were perforated. During their first laparotomy all 14 cases had a decompressive
      enterostomy without resection. 21 reoperations were later needed in these 14
      patients: simple enterostomy closure was performed in only 1 case, while
      resection of delayed strictures was required in 13. 12 cases underwent partial
      colectomy, 3 of these had multiple segmental resections for skip lesions and only
      1 child had a total colectomy. The only postoperative complication was one
      anastomotic leak. Two children had short-gut syndrome but later outgrew their
      need for parenteral nutrition. Our experience does not support the need of
      resecting the gangrenous bowel in the acute phase. A simple diverting enterostomy
      seems to be effective treatment. Delaying the intestinal resection up to the time
      of recanalisation allows spontaneous healing and results in the sparing of a
      significant length of bowel.

PMID- 8740132
TI  - Familial aplasia cutis congenita.
AB  - Two siblings with extensive aplasia cutis congenita of the extremities are
      described. These lesions healed spontaneously and in the older sibling at four
      years follow-up there was minimal scar tissue at the affected sites.

PMID- 8740133
TI  - Thrombosis of the arterial cannula during extracorporeal membrane oxygenation in
      a full-term newborn infant.
AB  - The authors report a rare case of cannula thrombosis during extracorporeal
      membrane oxygenation (ECMO). A full-term newborn infant was successively placed
      on single-cannula veno-venous extracorporeal lung support and then on veno
      arterial ECMO, because of persistent pulmonary hypertension. At 140 hours of
      ECMO, the infant displayed general cyanosis except in the right arm. Since
      asymmetric hypoxemia during ECMO may be related either to cannula malposition or
      to a tip thrombosis, a chest x-ray after contrast injection into the arterial
      line of the circuit was performed. It showed an opacification of the whole
      cannula but for the last distal centimeter, and of the vascular bed extending
      from the right subclavian artery. Cannula thrombosis was suspected and confirmed
      by removal of the arterial cannula. Demonstration of cannula thrombosis by
      opacification of the arterial line of the circuit indicates catheter removal.

PMID- 8740134
TI  - Traumatic pneumatoceles in an infant: case report and review of the literature.
AB  - A female infant who was run over by a tractor was admitted to an outside trauma
      unit. In addition to severe intraabdominal injuries, she sustained blunt chest
      trauma. In the right lung she developed pneumatoceles 48 hours after the trauma
      which were misinterpreted as pneumothorax on repeated chest x-rays. Several
      attempts to drain the right pleural cavity failed and the patient died five days
      after the trauma just before referral. Compression of an elastic thorax is
      followed by a greatly increased negative intrathoracic pressure on chest rebound
      and this sequence of events causes bursting lesions of the lung resulting in
      traumatic intrapulmonary cysts, the so-called pneumatoceles. One must be aware
      that pneumatoceles can develop and initial diagnosis is difficult. Although
      usually uncomplicated, a pneumatocele that does not progressively become smaller
      can be a life-threatening complication of blunt chest trauma and surgical
      resection is recommended.

PMID- 8740135
TI  - Extra-lobar intra-abdominal pulmonary sequestration.
AB  - An ultrasonography scan detected a left upper quadrant abdominal mass in a fetus
      of 20 weeks gestation. The mass was confirmed by a postnatal ultrasonography
      scan, computerized tomography and magnetic resonance imaging prior to surgery.
      The sonographic characteristic of this lesion was that of a homogenous echogenic
      mass embedded in the left diaphragmatic crus, which moved with respiration.
      Histopathological evaluation of the mass demonstrated alveolar and bronchial
      tissue, with its own visceral pleural covering corroborating the diagnosis of
      extra-lobar intra-abdominal pulmonary sequestration. Surgical excision is a valid
      recommendation because of the uncertainty of preoperative diagnosis of this
      uncommon malformation.

PMID- 8740136
TI  - Extrapyramidal disorder secondary to cytomegalovirus infection and toxoplasmosis
      after liver transplantation.
AB  - A boy underwent liver transplantation for postnecrotic cirrhosis secondary to
      Wilson's disease. The patient had no neurological clinical manifestations prior
      to the transplantation. The patient developed dysarthria, dysphagia, spasticity,
      rigidity, and intention and resting tremor of all extremities. Cranial
      computerized tomography revealed hypodensity of the thalamus, basal ganglia and
      external capsule. Anti-cytomegalovirus IgM became positive. At autopsy, there
      were severe pathological changes at the thalamus and basal ganglia.

PMID- 8740137
TI  - Duplication of appendix with segmental dilatation of the colon, myeloschisis and
      anal atresia.

PMID- 8740138
TI  - The Currarino syndrome--hereditary transmitted syndrome of anorectal, sacral and
      presacral anomalies. Case report and review of the literature.
AB  - The Currarino triad is a hereditary transmitted syndrome, originally defined by
      Currarino as ASP-association, consisting of an anorectal malformation, a sacral
      bony defect and a presacral mass. In most cases autosomal dominant transmission
      is suggested. In family members one or two features of the syndrome may be
      missing, indicating an incomplete form of this complex. We describe two unrelated
      girls at the age of 8 and 9 months respectively with ASP-association. Family
      screening in both patients showed 8 additional cases with a complete or
      incomplete Currarino triad, four of them being asymptomatic. A review of the
      literature up to 1991 revealed 48 patients with ASP-association. In more than 80%
      of cases, this complex is diagnosed in the first decade, whereas incomplete
      Currarino syndrome is diagnosed predominantly in adults. Most frequently the
      presacral mass in ASP-association was reported to be an anterior meningocele
      (47%) and a benign teratoma (40%). The number of patients with Currarino syndrome
      has been underestimated so far. We recommend anorectal examination, pelvic
      ultrasound and pelvic x-rays in all patients with a history of chronic
      constipation since early childhood. Positive findings should lead to further
      investigations such as barium enema, MRI, myelography and family screening. Close
      cooperation between pediatric surgeons and neurosurgeons is required to ensure
      adequate surgical treatment, considering both the risk of malignant degeneration
      as well as the risk of intraoperative nerve damage. Thus, radical excisional
      surgery is not obligatory in every case of Currarino syndrome.

PMID- 8740139
TI  - The tachykinin NK1 receptor mediates the migration-promoting effect of substance
      P on human skin fibroblasts in culture.
AB  - Fibroblast migration is an important component of the tissue response during the
      repair process, and substance P (SP) has been shown to exert trophic effects. In
      the present study, cell migration was evaluated as the distance travelled by
      adherent human skin fibroblasts (HF) at 96 h and by the number of individual
      cells moving across a filter within 5 h. In control conditions (1% calf serum)
      adherent fibroblasts moved from the starting line by approximately 700 microns.
      The addition of SP (10(-11)-10(-7) M) increased HF mobilisation in a
      concentration-dependent manner, with maximal activity at 10(-8) M (50% increase
      in migration over control). Migration of individual HF in suspension was also
      promoted by SP in a concentration-dependent manner, with an EC50 of 2.2 x 10(-9)
      M. The response produced by the maximally effective concentration of SP was equal
      to 65 and 90% of the effect elicited by 100 ng/ml Platelet-Derived Growth Factor
      A/B (PDGF A/B) on adherent and individual cells respectively. The synthetic NK1
      receptor agonist [Sar9]SP-sulphone (10(-11)-10(-6) M) reproduced the SP effect.
      The NK2 and NK3 receptor agonists [beta Ala8]NKA(4-10) and [MePhe7]NKB were
      devoid of any effect. The effect of SP was antagonised by two selective
      antagonists of NK1 receptors, namely (+/-) CP 96,345 (10(-10)-10(-8) M) and FK
      888 (10(-9)-10(-7) M), while the NK2 receptor antagonist MEN 10627 (10(-8)-10(-7)
      M) was not effective. Our data indicate that SP is a potent effector of
      fibroblast migration and the NK1 receptor is responsible for this effect. These
      observations further support the specific role of the NK1 receptor in mediating
      the trophic function of SP at the cutaneous level.

PMID- 8740140
TI  - Potencies of antagonists chemically related to iodoproxyfan at histamine H3
      receptors in mouse brain cortex and guinea-pig ileum: evidence for H3 receptor
      heterogeneity?
AB  - We determined the affinities of 16 newly synthesized H3 receptor antagonists in
      an H3 receptor binding assay and the potencies of 12 of these compounds at
      functional H3 receptors in the mouse brain cortex and guinea-pig ileum. The
      compounds differ from histamine in that the C-C-N side chain is replaced by a
      chain of the structure C-C-C-O. The two major aims of the study were (1) to
      investigate whether the two functional H3 receptors are pharmacologically
      different and (2) to derive structure-activity relationships. The specific
      binding of 3H-Na-methylhistamine to rat brain cortex membranes was monophasically
      displaced by each of the 16 compounds at pKi values ranging from 7.30 to 9.48. In
      superfused mouse brain cortex slices preincubated with 3H-noradrenaline, the
      electrically evoked tritium overflow was slightly decreased by iodoproxyfan and
      its deiodo analogue; this effect was counteracted by the H3 receptor antagonist
      clobenpropit. The other compounds did not affect the evoked tritium overflow by
      themselves. The concentration-response curve of histamine for its inhibitory
      effect on the electrically evoked tritium overflow was shifted to the right by
      the 12 compounds with apparent pA2 values ranging from 7.02 to 9.00. The 12
      compounds also shifted to the right the concentration-response curve of R-a
      methylhistamine for its inhibitory effect on the electrically induced contraction
      in guinea-pig ileum strips; the apparent pA2 values ranged from 5.97 to 9.00.
      Iodoproxyfan decreased the electrically induced contraction by itself and this
      effect was counteracted by the H3 receptor antagonist thioperamide. The apparent
      pA2 values in the two functional H3 receptor models showed a highly significant
      correlation (r = 0.882; P < 0.001). Highly significant correlations were also
      obtained when the pKi values of the compounds in the binding assay were compared
      to their apparent pA2 values in the mouse brain (r = 0.799; P < 0.004) and in the
      guinea-pig ileum (r = 0.851; P < 0.001). In each of the three experimental
      models, iodoproxyfan was the most potent compound; its deiodo analogue was less
      potent by more than 1.1 log units. The present results show that the compounds
      under study possess moderate to high affinity and/or (partial) H3 receptor
      antagonist potency. The two functional H3 receptors in the mouse brain cortex and
      the guinea-pig ileum may be slightly different; further studies are necessary to
      clarify whether this difference is due to H3 receptor heterogeneity, species
      variants or differences in the efficiency of receptor coupling. The marked
      difference in the affinity/potency between iodoproxyfan and its deiodo analogue
      may suggest that a highly lipophilic residue in that part of the molecule favours
      a high affinity/antagonistic potency at H3 receptors.

PMID- 8740141
TI  - Characterization of 5-hydroxytryptamine (5-HT) receptor subtypes influencing
      colonic motility in conscious dogs.
AB  - We examined the effects of exogenous 5-hydroxytryptamine (5-HT) and selective 5
      HT receptor agonists and antagonists on proximal, middle and distal colonic
      motility in conscious fasted dogs with extraluminal force transducers implanted
      chronically. 5-HT (0.003-0.1 mg/kg i.v.) dose-dependently enhanced motility along
      the entire length of the colon. The 5-HT (0.03 mg/kg i.v.)-induced response was
      inhibited by 0.1-1.0 mg/kg i.v. methysergide, a 5-HT1/2 antagonist, at all
      recording sites and by 0.1-1.0 mg/kg i.v. ketanserin, a 5-HT2A antagonist, at the
      middle and distal sites only. At 1 mg/kg i.v., YM060, a 5-HT3 antagonist, reduced
      the amplitude of the initial transient high-amplitude contractions induced by 5
      HT, but did not affect the tonic contraction induced by 5-HT. At doses up to 3
      mg/kg i.v., 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino) ethyl ester
      (SDZ205-557), a 5-HT4 antagonist, and hexamethonium (up to 10 mg/kg i.v.) did not
      affect 5-HT-induced responses at any recording site. Renzapride, a 5-HT4 agonist,
      also stimulated motility along the entire length of the colon at 0.3 mg/kg i.v..
      The renzapride-induced response was inhibited by 1 mg/kg i.v. SDZ205-557 or 3
      mg/kg i.v. hexamethonium. m-Chlorophenylbiguanide (m-CPBG), a 5-HT3 agonist, (1
      mg/kg i.v.) produced a transient high-amplitude contraction at all recording
      sites and this contraction was eliminated by pretreatment with 0.03 mg/kg i.v.
      YM060. The contraction produced by m-CPBG declined rapidly, so the increase in
      the motility index by m-CPBG was not significant at any recording site. Of the
      antagonists tested, 0.1-1 mg/kg i.v. methysergide produced a delayed and
      prolonged contractile response at the middle and distal sites. The onset of the
      response was delayed about 20 min after application and the response was
      maintained over the subsequent 60-min observation period. The methysergide (1
      mg/kg i.v.)-induced response was inhibited by 3 mg/kg i.v. hexamethonium. The
      other antagonists, ketanserin, YM060 and SDZ205-557, had no contractile effect at
      any recording site. These results indicate that exogenous 5-HT stimulates
      motility along the entire length of the fasted canine colon and that 5-HT-induced
      responses in the proximal colon are mediated mainly by 5-HT1, whereas those in
      the middle and distal colon are mediated by both 5-HT1 and 5-HT2 receptors.
      Renzapride and methysergide also stimulate colonic motility via additional
      mechanisms. The activation of 5-HT4 receptors and the blockade of endogenous 5-HT
      inhibitory regulation via 5-HT1 receptors may be involved in the action of
      renzapride and methysergide respectively.

PMID- 8740142
TI  - Selective enhancement by an adenosine A1 receptor agonist of agents inducing
      contraction of the rat vas deferens.
AB  - The adenosine analogue N6-cyclopentyladenosine (CPA), acting via postjunctional
      A1 receptors, has been shown to enhance contractions of the rat vas deferens
      induced by adenosine 5'-triphosphate (ATP), the sympathetic cotransmitter in this
      tissue. The aim of the present study was to examine the ability of CPA to enhance
      contractions induced by other contractile agents. CPA (0.01-0.3 microM) enhanced
      contractions induced by exogenous ATP (10 microM), 5-hydroxytryptamine (5-HT) (3
      microM), tyramine (10 microM), 2-methyl-5-hydroxytryptamine (2-Me-5-HT) (10
      microM) and KCl (35 mM) and this enhancement was blocked by an A1-selective
      concentration (3 nM) of 1, 3-dipropyl-8-cyclopentylxanthine (DPCPX). CPA failed
      to enhance contractions induced by exogenous noradrenaline (NA) (1 microM or 10
      microM), bradykinin (0.1 microM), phenylephrine (3 microM) or carbachol (10
      microM). The contractions induced by ATP (10 microM), 5-HT (3 microM), 2-Me-5-HT
      (10 microM) and KCl (35 mM) were unaffected by tetrodotoxin (1 microM) as well as
      by desensitisation of the P2x-purinoceptors with the ATP analogue adenosine 5'
      (alpha, beta-methylene) triphosphonate. The contractions induced by tyramine (10
      microM) and 2-Me-5-HT (10 microM) were blocked by prazosin (100 nM) or by
      imipramine (1 microM). Ketanserin (10 nM) antagonised the response to 5-HT giving
      a dose-ratio of 12.9 corresponding to an apparent pA2 of 9.1. In conclusion, the
      A1-mediated effect was clearly selective for certain contractile agents and not
      due to a non-specific increase in contractility of the tissue. CPA enhanced
      contractions induced by both ATP and indirect sympathomimetics which release
      endogenous NA, and this enhancement of the two sympathetic cotransmitters may
      have a functional significance, and demonstrates the complexity of the
      neuromodulatory effects of adenosine in the rat vas deferens.

PMID- 8740143
TI  - Evidence against a regulation of Na+/K(+)-ATPase by Gi proteins. Failure to
      detect an influence of G proteins on Na+/Ca(2+)-exchange in cardiac sarcolemmal
      membranes.
AB  - In the myocardium the inhibitory guanine nucleotide-binding regulatory proteins
      (Gi proteins) mediate negative chronotropic and negative inotropic effects by
      activation of K+ channels and inhibition of adenylyl cyclase. The concept of a
      uniform inhibitory action of Gi proteins on myocardial cellular activity has been
      questioned by the recent observations of adenosine-induced activation of the
      Na+/Ca(2+) exchange and a carbachol-induced inhibition of the Na+/K(+)-ATPase
      activity in cardiac sarcolemmal membranes. The aim of the present study,
      therefore, was to reinvestigate the putative regulation of Na+/Ca(2+) exchange
      and Na+/K(+)-ATPase activity in purified canine sarcolemmal membranes. These
      membranes were enriched in adenosine A1 (Maximum number of receptors, Bmax 0.033
      pmol/mg) and muscarinic M2 (Bmax 2.9 pmol/mg) receptors and contained Gi2 and
      Gi3, two Gi protein isoforms, and G0, another pertussis toxin-sensitive G
      protein, as detected with specific antibodies. The adenosine A1-selective
      agonist, (-)-N6-(2-phenylisopropyl)-adenosine, and the muscarinic agonist,
      carbachol, both inhibited isoprenaline-stimulated adenylyl cyclase activity by
      25% and 35% respectively, and the stable GTP analogue 5'-guanylylimidodiphosphate
      inhibited forskolin-stimulated adenylyl cyclase activity by 35% in these
      membranes. The characteristics of Na+/Ca(2+) exchange and Na+/K(+)-ATPase
      activity as well as those of the ouabain-sensitive, K(+)-activated 4
      nitrophenylphosphatase, an ATP-independent, partial reaction of the Na+/K(+)
      ATPase, were in agreement with published data with regard to specific activity,
      time course of activity and substrate dependency. However, none of these
      activities were influenced by adenosine, (-)-N6-(2-phenylisopropyl)-adenosine,
      carbachol, or stable GTP analogs, suggesting that Na+/Ca(2+) exchange and
      Na+/K(+)-ATPase are not regulated by Gi proteins in canine cardiac sarcolemmal
      membranes.

PMID- 8740144
TI  - Inhibition of T cell cAMP formation by cyclosporin A and FK506.
AB  - The influence of the immunosuppressants, cyclosporin A (CsA) and FK506, on cAMP
      formation was studied in T cells from healthy controls and patients with
      psoriasis. While basal cAMP levels were not affected, CsA (1 microM) and FK506 (2
      nM) prevented the isoprenaline (0.1 microM)-induced increase in cAMP formation.
      Half-maximal inhibition by FK506 and CsA was observed at about 0.2 nM and 20 nM,
      respectively. In addition, both agents significantly reduced (by about 50%) the
      forskolin (8 microM)-stimulated cAMP formation. No differences were noted in cAMP
      responses (basal, stimulation by isoprenaline, inhibition by CsA and FK506) of T
      cells from healthy controls and psoriatic patients. We conclude that CsA and
      FK506 potently and efficiently interfere with the stimulatory adenylyl cyclase
      pathway in T cells and that regulation of T cell cAMP formation is apparently not
      altered in psoriasis.

PMID- 8740145
TI  - The impact of a competitive and a non-competitive NMDA receptor antagonist on
      dopaminergic neurotransmission in the rat ventral tegmental area and substantia
      nigra.
AB  - The study compares effects of the competitive and non-competitive NMDA receptor
      antagonists, CGP 40116 and MK-801 respectively, on the metabolism of dopamine and
      on the density of D-1 and D-2 dopaminergic receptors in the rat ventral tegmental
      area and substantia nigra. The effects of CGP 40116 were tested in a range of
      doses which either were devoid of or had locomotor- or stereotypy-stimulating
      effects. It was found that (1) CGP 40116 given in a dose of 5 mg/kg enhanced the
      locomotor activity of rats and evoked a stereotypy-like activity; doses of 1.25
      and 2.5 mg/kg were devoid of such effects; (2) CGP 40116 (5 mg/kg) enhanced the
      concentrations of dopamine, DOPAC and HVA in the ventral tegmental area, whereas
      the lowest dose, 1.25 mg/kg was without effect; a dose of 2.5 mg/kg increased the
      concentration of dopamine only; the only effect of CGP 40116 (5 mg/kg) observed
      in substantia nigra, was an increase in dopamine concentration; its doses of 1.25
      and 2.5 mg/kg were ineffective. (3) MK-801 (0.2 and 0.4 mg/kg) enhanced the
      concentrations of dopamine, DOPAC and HVA in both structures. A dose of 0.1 mg/kg
      increased the dopamine concentration only. The effects of MK-801 in substantia
      nigra were quantitatively weaker than those observed in ventral tegmental area.
      (4) Both CGP 40116 (5 mg/kg) and MK-801 (0.4 mg/kg) evoked alterations in the
      density of dopaminergic receptors. D-2 receptors, were up-regulated by MK-801 in
      ventral tegmental area and subregions of substantia nigra, i.e. pars compacta and
      pars reticulata, whereas CGP 40116 evoked similar effects in ventral tegmental
      area only. D-1 receptors in pars compacta and pars reticulata of substantia nigra
      were down-regulated after administration of either drug. It is concluded that
      competitive NMDA receptor antagonists in doses which evoke hyperlocomotion and
      stereotypy-like activity, may have a substantial impact on the dopaminergic
      neurotransmission in the rat ventral tegmental area and substantia nigra, similar
      to that described for MK-801, a non-competitive NMDA receptor antagonist. The
      obtained results may suggest that CGP 40116 and, possibly, other competitive NMDA
      antagonists may have dopaminomimetic properties, and that their clinical
      potentials may be limited by the risk of evoking dopamine-dependent
      psychotomimetic and abusing effects, similar to those described for MK-801.

PMID- 8740146
TI  - Evidence for uptake1-mediated efflux of catecholamines from pulmonary endothelial
      cells of perfused lungs of rats.
AB  - Previous pharmacological studies have demonstrated that pulmonary endothelial
      cells and noradrenergic neurones possess the same transporter for inward
      transport of catecholamines, uptake1. In noradrenergic neurones, it has been
      shown that uptake1 is also involved in the carrier-mediated outward transport, or
      efflux, of noradrenaline and dopamine. The aim of the present study was to
      examine the efflux of noradrenaline and dopamine from perfused lungs of rats to
      determine whether uptake1, in addition to diffusion, mediates efflux of
      catecholamines from pulmonary vascular endothelial cells. The effects of reducing
      the cellular sodium gradient and of substrates and inhibitors of uptake1 on the
      efflux of 3H-noradrenaline and 3H-dopamine from rat lungs were measured. Isolated
      perfused lungs of rats (monoamine oxidase and catechol-O-methyltransferase
      inhibited) were loaded with 3H-(-)-noradrenaline or 3H-dopamine for 10 min
      followed by perfusion with either (1) a low sodium, amine-free Krebs solution, in
      which NaCl was replaced by either Tris.HCl or LiCl, for 15 or 10 min,
      respectively or (2) amine-free Krebs solution for 30 min in the absence or
      presence of a substrate or inhibitor of uptake1 for the last 15 min. The rate
      constants for spontaneous efflux of noradrenaline and dopamine from the lungs
      were 0.0163 min-1 and 0.0466 min-1, respectively. When NaCl was replaced by
      Tris.HCl during efflux, the rate constants for efflux of noradrenaline and
      dopamine were increased 2.5-fold and 3-fold, respectively, whereas, when NaCl was
      replaced by LiCl, the rate constants were increased 8-fold and 4-fold,
      respectively. The uptake1 substrates, dopamine (1 and 3 mumol/l) and adrenaline
      (40 mumol/l), both caused a rapid and marked increase in the efflux of
      noradrenaline, while noradrenaline (4 mumol/l) had a similar effect on the efflux
      of dopamine. The uptake1 inhibitors, imipramine (3 and 10 mumol/l) and nisoxetine
      (50 nmol/l), caused small and gradual increases in the efflux of noradrenaline
      and dopamine from rat lungs. These results demonstrate that efflux of
      noradrenaline and dopamine from rat lungs is affected by alterations in the
      normal sodium gradient across the cell and by drugs that interact with the
      uptake1 transporter. Thus, it can be concluded that the spontaneous efflux of
      catecholamines from pulmonary vascular endothelial cells is mediated
      predominantly by uptake1. In addition, efflux of catecholamines from the lungs
      has a diffusional component, which, combined with inhibition of reuptake,
      accounts for the small increase in amine efflux by inhibitors of uptake1.

PMID- 8740147
TI  - Amezinium and debrisoquine are substrates of uptake1 and potent inhibitors of
      monoamine oxidase in perfused lungs of rats.
AB  - Previous studies have resulted in the classification of amezinium as a selective
      inhibitor of neuronal monoamine oxidase (MAO), because it is a much more potent
      MAO inhibitor in intact tissues, in which it is accumulated in noradrenergic
      neurones by uptake1, than in tissue homogenates. In the present study, the
      effects of amezinium on the deamination of noradrenaline were investigated in
      intact lungs of rats, since the pulmonary endothelial cells are a site where the
      catecholamine transporter is non-neuronal uptake1. In addition, another drug that
      is both a substrate of uptake1 and a MAO inhibitor, debrisoquine, was
      investigated in the study. The first aim of the study was to show whether
      amezinium and debrisoquine are substrates of uptake1 in rat lungs. After loading
      of isolated perfused lungs with 3H-noradrenaline (MAO and catechol-O
      methyltransferase (COMT) inhibited), the efflux of 3H-noradrenaline was measured
      for 30 min. When 1 mumol/l amezinium or 15 mumol/l debrisoquine was added for the
      last 15 min of efflux, there was a rapid and marked increase in the fractional
      rate of loss of 3H-noradrenaline, which was reduced by about 70% when 1 mumol/l
      desipramine was present throughout the efflux period. These results showed that
      both drugs were substrates for uptake1 in rat lungs. In lungs perfused with 1
      nmol/l 3H-noradrenaline (COMT inhibited), 10, 30 and 300 nmol/l amezinium caused
      58%, 76% and 74% inhibition of noradrenaline deamination, respectively, and 30,
      300 and 3000 nmol/l debrisoquine caused 56%, 89% and 96% inhibition of
      noradrenaline deamination, respectively. When MAO-B was also inhibited, 10 nmol/l
      amezinium caused 84% inhibition of the deamination of noradrenaline by MAO-A in
      the lungs. In contrast, in hearts perfused with 10 nmol/l 3H-noradrenaline under
      conditions where the amine was accumulated by uptake2 (COMT, uptake1 and
      vesicular transport inhibited), 10 nmol/l amezinium had no effect and 300 nmol/l
      amezinium caused only 36% inhibition of deamination of noradrenaline. The results
      when considered with previous reports in the literature show that amezinium is
      about 1000 times more potent and debrisoquine is about 20 times more potent for
      MAO inhibition in rat lungs than in tissue homogenates, and the reason for their
      high potencies in the intact lungs is transport and accumulation of the drugs in
      the pulmonary endothelial cells by uptake1. Amezinium is much less potent as a
      MAO inhibitor in cells with the uptake2 transporter, such as the myocardial cells
      of the heart. The results also confirmed previous reports that amezinium is
      highly selective for MAO-A.

PMID- 8740148
TI  - Effects of cocaine on the EEG power spectrum of rats are significantly altered
      after its repeated administration: do they reflect sensitization phenomena?
AB  - It was previously shown that a moderate dose of cocaine (10 mg/kg i.p.) produces
      a pattern in the EEG power spectrum which indicates a preferential activation of
      dopamine D1-like receptors, namely a decrease of power in most of the frequency
      bands. In contrast, a large dose of cocaine (30 mg/kg i.p.) produces a decrease
      of power in most of the frequency bands as well, but a selective increase in the
      alpha-1 band, characteristic for an additional activation of dopamine D2-like
      receptors. In the present experiments, it was studied in rats, if in the course
      of sensitization, a shift from D1-like to additional D2-like receptor activation
      will occur or not. For this study, the animals were treated 10 times with cocaine
      (either 10 or 20 mg/kg) and, after a drug free interval of 4 days, tested with
      the same dose administered previously. Acute administration of 10 mg/kg of
      cocaine increased the locomotor activity slightly and its effect tended to be
      enhanced after repeated administration. Twenty mg/kg cocaine increased the
      locomotor activity more than the 10 mg/kg dose and its effect was significantly
      enhanced after repeated treatment. In addition, it was shown that the dose of 10
      mg/kg of cocaine which activates D1- but not D2-like receptors is sufficient to
      elicit conditioned place preference. Ten mg/kg of cocaine produced a decrease of
      power in most of the frequency bands and this effect was slightly more pronounced
      after repeated treatment. Twenty mg/kg of cocaine acutely also produced a
      decrease in power in most of the frequency bands, but did not decrease the power
      in the alpha-1 band, being just at the threshold of activating D2-like receptors
      as well. Repeated administration led to a significant increase in power in the
      alpha-1 band and a less pronounced one in the alpha-2 band. This observation
      demonstrates that sensitization to cocaine can be manifest in the EEG and that
      after a certain dosage, a shift from an activation of D1-like dopamine receptors
      to an additional activation of D2-like receptors becomes obvious.

PMID- 8740149
TI  - Effects of antimigraine drugs on retinal spreading depression.
AB  - It has been suggested that spreading depression may play a role in triggering
      classical migraine. In this study the retinal spreading depression was used as a
      pharmacological tool to test the neuronal effects of several common antimigraine
      drugs. As the chicken retina is void of any blood vessels the observed effects
      must be of pure neuronal origin. It is shown that propranolol, sumatriptan,
      methysergide, paracetamol and acetylsalicyclic acid decrease the propagation
      velocity of retinal spreading depression waves, accelerate the recovery of the
      optical and electrical signal and reduce the amplitude of the negative potential
      shift, concomitant with the spreading depression. Barbiturate increases the
      spreading velocity, and the amplitude of the potential shift. Ergotamine,
      clonidine, lisuride and iprazochrome have no significant influence on retinal
      spreading depression.

PMID- 8740150
TI  - No evidence for functional imidazoline receptors on locus coeruleus neurons.
AB  - alpha 2-Adrenoceptor agonists inhibit the firing of locus coeruleus (LC) neurons.
      It was recently observed that the alpha-adrenoceptor agonists clonidine,
      rilmenidine and cirazoline, when injected intravenously in anaesthetized rats
      pretreated with the irreversible alpha 2-adrenoceptor antagonist N-ethoxycarbonyl
      2-ethoxy-1,2-dihydroquinoline (EEDQ), excite the LC. The effect was attributed to
      activation of I1 imidazoline receptors. The aim of the present experiments was to
      characterize the direct effect of alpha 2-adrenoceptor and I1 imidazoline
      receptor agonists on LC neurons. Electrical activity of LC neurons was
      extracellularly recorded in midpontine slices prepared from the rat brain.
      Concentration-response curves were obtained for the alpha 2-agonist noradrenaline
      and the mixed I1/alpha 2-receptor agonists clonidine, rilmenidine and moxonidine
      in slices without treatment and in slices treated with 6-chloro-N-methyl-2,3,4,5
      tetrahydro-1H-3-benzazepine (SK&F86466) or EEDQ, alpha 2-adrenoceptor antagonists
      with low affinity for I1 and I2 imidazoline receptors, respectively. All four
      agonists concentration-dependently reduced the firing rate of the neurons, with
      full inhibition at higher concentrations. SK&F86466 shifted the concentration
      response curves of the agonists to the right; the calculated antagonist
      dissociation constants are compatible with an effect of the agonists on alpha 2
      adrenoceptors. EEDQ completely prevented the inhibition by the agonists. Neither
      in SK&F86466- nor in EEDQ-treated slices was an excitation by clonidine,
      rilmenidine and moxonidine observed. We conclude that the LC neurons do not
      possess functional I1 (and also no I2) imidazoline receptors. The effects of
      noradrenaline, clonidine, rilmenidine and moxonidine on the neurons can be fully
      explained with an interaction with inhibitory alpha 2-adrenoceptors (probably of
      the alpha 2D subtype). The excitation of the LC by imidazoline receptor agonists
      under in vivo conditions, hence, is not a direct effect on the neurons of the LC.

PMID- 8740151
TI  - Opposite modulation of noradrenaline and ATP release in guinea-pig vas deferens
      through prejunctional beta-adrenoceptors: evidence for the beta 2 subtype.
AB  - Activation of prejunctional beta-adrenoceptors has been suggested to increase the
      release of noradrenaline but to decrease the neural release of ATP in the guinea
      pig vas deferens. Experiments were carried out to determine the subtype of beta
      adrenoceptor involved. In [3H]-noradrenaline-preincubated tissues superfused with
      medium containing prazosin and suramin, isoprenaline (1-100 nM), salbutamol (0.01
      1 microM) and terbutaline (0.1-10 microM) increased the overflow of tritium but
      reduced the overflow of ATP elicited by electrical stimulation (210 pulses/7 Hz).
      The effects of isoprenaline were blocked by the beta 2-selective antagonist 1
      [2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3- [(1-methylethyl)amino]-2-butanol
      (ICI 118,551; 100 nM). In prazosin- and suramin-free medium, isoprenaline (100
      nM) did not change the overflow of ATP elicited by exogenous noradrenaline (10
      microM). Isoprenaline (1-100 nM), salbutamol (0.01-1 microM) and terbutaline (0.1
      10 microM) reduced the initial twitch contraction elicited by electrical
      stimulation (210 pulses/7 Hz) in prazosin- and suramin-free medium as well as the
      isolated purinergic neurogenic contraction obtained by exposure to prazosin. They
      increased or tended to increase the secondary sustained concentration elicited by
      electrical stimulation in prazosin- and suramin-free medium as well as the
      isolated adrenergic neurogenic contraction obtained in the presence of suramin.
      The inhibition by isoprenaline of the isolated purinergic contraction was
      attenuated by ICI 118,551 (100 nM) but not by the beta 1-selective antagonist 1
      [2-((3-carbamoyl- 4-hydroxy)phenoxy)ethylamino]-3-[4-(1-methyl-4- trifluoromethyl
      2-imidazolyl)phenoxy]-2-propanol (CGP 20712A; 100 nM). The results confirm the
      opposite beta-adrenoceptor-mediated modulation of noradrenaline and neural ATP
      release in the guinea-pig vas deferens. They show that the prejunctional beta
      adrenoceptor is of the beta 2-subtype.

PMID- 8740152
TI  - Inhibitory effects of propofol on catecholamine secretion and uptake in cultured
      bovine adrenal medullary cells.
AB  - In the central and peripheral noradrenergic neurons, the balance between
      noradrenaline release and reuptake determines the level of noradrenaline at the
      synaptic cleft or the nerve ending. In the present study, we examined the effects
      of propofol, an intravenous general anaesthetic, on catecholamine secretion and
      noradrenaline uptake in cultured bovine adrenal medullary cells and on the serum
      noradrenaline and blood pressure in rats. In cultured adrenal medullary cells,
      propofol (10-50 mumol/l) concentration-dependently inhibited catecholamine
      secretion stimulated by carbachol. Propofol suppressed carbachol-evoked 22Na+
      influx as well as 45Ca2+ influx at concentrations similar to those which
      suppressed the catecholamine secretion. Propofol (10-50 mumol/l) also inhibited
      veratridine-evoked 22Na+ influx, 45Ca2+ influx and catecholamine secretion,
      whereas it had little effect on the 45Ca2+ influx and catecholamine secretion
      induced by 56 mmol/l K+. Cultured adrenal medullary cells show [3H] noradrenaline
      uptake which is sensitive to imipramine. Propofol (10-50 mumol/l) significantly
      inhibited the imipramine-sensitive uptake of [3H] noradrenaline. In rats,
      intravenous administration of propofol (2.5 mg/kg) lowered serum noradrenaline
      and arterial blood pressure. From these findings, in spite of inhibiting
      noradrenaline uptake, propofol at anaesthetic concentrations (10-30 mumol/l)
      seems to reduce catecholamine secretion by interfering with Na+ influx through
      voltage-dependent Na+ channels as well as nicotinic acetylcholine receptor
      associated ion channels in the adrenal medulla and, probably, in the sympathetic
      nervous system. This may explain the propofol-induced hypotension during
      anaesthesia.

PMID- 8740153
TI  - Homogeneous or heterogeneous distribution of systemically administered
      adrenaline: organ dependence.
AB  - In incubation experiments it was shown that exogenous adrenaline or noradrenaline
      does not distribute homogeneously into the adrenergic varicosities of the rat vas
      deferens (wall with thick and compact muscle layer) but does distribute
      homogeneously in the rat spleen capsule (thin and loose muscle layer, containing
      more extracellular space than the vas deferens). To circumvent any hypothetical
      role of the muscular layer in the distribution of the amine, 100 micrograms.kg
      1.h-1 adrenaline was administered to rats in vivo either i.v. (during 90 min) or
      i.p. (under pentobarbital anaesthesia, an Alzet minipump was implanted which
      delivered that dose during 6 days). The rats also received 100 mg.kg-1 pargyline
      (to inhibit MAO) and 100 mg.kg-1 tropolone (to inhibit COMT). At the end of
      adrenaline administration, vasa deferentia and spleen capsule were removed,
      washed and then exposed to 100 mumol.l-1 tyramine for 20 min. At the end of this
      exposure, the ratio noradrenaline/adrenaline in the tissue and in the medium was
      compared. In the vas deferens both after i.v. and i.p. administration of
      adrenaline, the ratio noradrenaline/adrenaline was about 3 times higher in the
      medium than in the tissue, while in the spleen capsule the ratio
      noradrenaline/adrenaline was not significantly different in the medium and in the
      tissue. We conclude that, even when the amine reaches the storage sites from the
      blood, it distributes homogeneously in the spleen capsule and heterogeneously in
      the vas deferens, perhaps because there are more than one kind of storage
      vesicles in the vas deferens.

PMID- 8740154
TI  - Contraction and relaxation of aortas from diabetic rats: effects of chronic anti
      oxidant and aminoguanidine treatments.
AB  - We examined whether chronic treatment with the free radical scavengers butylated
      hydroxytoluene (1 g kg-1 day-1) and N-acetyl-L-cysteine (250 mg kg-1 day-1), or
      the inhibitor of advanced glycosylation reactions, aminoguanidine (1 g kg-1 day
      1), could prevent the development of relaxation and contraction abnormalities in
      aorta from 2 month streptozotocin-diabetic rats. Diabetes caused a 24% deficit in
      maximal endothelium-dependent relaxation to acetylcholine for phenylephrine
      precontracted aortas (P < 0.01). This was unaffected by tissue-bath glucose
      concentration (5.5 or 40 mM), or by addition of 1 mM L-arginine. Butylated
      hydroxytoluene, N-acetyl-L-cysteine and aminoguanidine treatments gave
      substantial protection, maximum relaxation remaining in the non-diabetic range.
      Neither diabetes nor treatment affected endothelium-independent relaxation to
      glyceryl trinitrate. To test the suggestion that aminoguanidine could act as an
      inhibitor of constitutive nitric oxide synthase, acute aminoguanidine effects on
      endothelium-dependent relaxation to acetylcholine were also examined. No
      inhibition was noted. A modest increase in phenylephrine sensitivity with
      diabetes (P < 0.05) was unaffected by butylated hydroxytoluene or N-acetyl-L
      cysteine, but partially prevented by aminoguanidine (P < 0.05). The data,
      therefore, provide evidence for the involvement of reactive oxygen species and
      the advanced glycosylation process particularly for impaired endothelium
      dependent relaxation in experimental diabetes.

PMID- 8740155
TI  - Comparison of the densities of 5-HT4 receptors, beta 1- and beta 2-adrenoceptors
      in human atrium: functional implications.
AB  - We measured in human atrium the density of 5-HT4 receptors, labelled with [125I]
      SB 207710 (1-butyl-4-piperidinyl) methyl 8-amino-7-iodo-1, 4-benzodioxan-5
      carboxylate), and compared it with the density of beta1- and beta2-adrenoceptors,
      labelled with (-)-[125I]-cyanopindolol. [125I]-SB 207710 (5-1200 pmol/l) labelled
      a small population of saturable binding sites (Bmax approximately 4 fmol/mg
      protein) with a pK(D) of 9.7 and with 5-HT4 receptor characteristics, as assessed
      with competing ligands. The density of atrial binding sites with 5-HT4 receptor
      characteristics was 10 and 5 times lower, respectively, than the density of beta
      1- and beta 2-adrenoceptors. We suggest that the small 5-HT4 receptor population
      may in part explain why the positive inotropic effects of 5-HT are smaller than
      those of catecholamines mediated through beta 1- and beta 2-adrenoceptors.

PMID- 8740156
TI  - Differential requirements for Ca2+ concentrations for catecholamine release and
      biosynthesis in isolated bovine adrenal chromaffin cells.
AB  - Differential effects of [Ca2+] on catecholamine release and biosynthesis in
      isolated bovine adrenal chromaffin cells were investigated. Carbamylcholine, an
      agonist of the nicotinic and muscarinic acetylcholine receptor, or Na+
      deprivation in the incubation medium, stimulated catecholamine release and
      biosynthesis in these cells. The concentrations of extracellular [Ca2+] which
      stimulate catecholamine biosynthesis were less than those which stimulate
      catecholamine release. An increase in intracellular levels of free Ca2+ ([Ca2+]i)
      induced by Na+ deprivation was dependent on extracellular [Ca2+]. These results
      indicate that, in bovine adrenal chromaffin cells, catecholamine biosynthesis is
      regulated by lower levels of [Ca2+]i than is catecholamine release.

PMID- 8740157
TI  - Twenty years of two-dimensional electrophoresis: past, present and future.

PMID- 8740158
TI  - Quantitative and automated electrophoresis in sieving media.

PMID- 8740159
TI  - Dynamics of DNA molecules in agarose gel under sinusoidal electric fields.
AB  - The dynamics of DNA molecules in agarose gel has been studied by measuring the
      birefringence in sine wave electric fields. It was found that the birefringence
      is the sum of a direct current (dc) component and several harmonics of the field
      frequency. A detailed study of these components was performed. It was found that
      the dynamics of DNA molecules under these conditions can be explained by a W
      conformation which is not detected under dc electric fields. The variation of the
      field frequency gives several relaxation modes in the birefringence signal,
      reflecting the known dynamic behavior of DNA molecules found in the reputation
      with elongation of the tube length regime.

PMID- 8740160
TI  - Detection and quantitation of specific mRNAs by ribonuclease protection assay
      using denaturing horizontal polyacrylamide gel electrophoresis: a radioactive and
      nonradioactive approach.
AB  - A radioactive (32P) and nonradioactive (digoxigenin) ribonuclease protection
      assay (RPA) has been developed to detect mRNAs of housekeeping proteins and
      growth factors. A modification of polyacrylamide gel electrophoresis (PAGE) to
      simplify RPA is described. Both Cleangels (Pharmacia) and laboratory-cast
      polyacrylamide gels, in a denaturing, horizontal electrophoresis system, were
      used. The amount of toxic chemicals and waste was reduced, in comparison with
      sequencing gels normally used for RPA. The protected RNA fragments were shown to
      be well-separated, with sufficient sensitivity in this modified, quick gel
      system.

PMID- 8740161
TI  - Electrophoretic separation of biopolymers in a matrix of polyacrylamide
      covalently linked to agarose.
AB  - A new type of agarose polyacrylamide mixed-bed gel, obtained by simultaneous
      gelation of a novel type of allyl-activated agarose and its copolymerization with
      acrylamide, has pore sizes intermediate between those of polyacrylamide and
      agarose. The process used to activate the agarose chains enables the substitution
      to be controlled. As indicated by nuclear magnetic resonance (NMR), only one
      allyl group was inserted per agarose basic unit. Several formulations of mixed
      bed gels, containing different percentages of acrylamide, were compared with
      conventional polyacrylamide or agarose gels. Resolution, migration distance and
      band sharpness of different molecular mass fragments were evaluated, with two
      types of gel run side-by-side in a vertical or horizontal system. The faster
      electrophoretic mobility of DNA in dilute mix-bed gels and the improved
      separation of the component of high molecular mass (1 to 6 kbp) of the 1 kbp
      ladder indicate that these matrices have larger porosity than any dilute
      polyacrylamide formulations. Sodium dodecyl sulfate (SDS)-protein complexes
      migrate in the mixed gels faster than in polyacrylamide gels of the same %T.

PMID- 8740162
TI  - Isoelectric focusing and titration curves in biomedicine and in agrofood
      industries: a multimedia teaching program.
AB  - The aim of this 45 min, 60 megabyte, modular program is to initiate students,
      scientists and engineers of biotechnology, biomedicine and agrofood industries
      into isoelectric focusing (IEF) and titration curves for analytical (e.g. IEF,
      zone electrophoresis, isotachophoresis, electrotransfer) and preparative (e.g.
      ion-exchange chromatography, chromatofocusing) application of charge-dependent
      methods. For advanced teaching, the following theoretical and practical aspects
      may be of interest: pH gradient engineering, IEF resolving power, generation of
      pH gradient, sample-ampholyte interactions, pH gradient drift, immobilized pH
      gradients (IPG), IPG-two-dimensional (2-D) electrophoresis, preparative methods
      with multi-compartments and IPG membranes, capillary IEF, isozyme analysis,
      etc.). The program associates fixed and animated drawings, and computer-assisted
      simulations, with spoken and written commentaries (in English). It is illustrated
      with numerous IEF gel patterns and titration curves and some video sequences to
      be run on a multimedia PC with MS Windows 3.1 (or later releases) as the only
      software. The linear presentation of the program may be used directly on the PC,
      or may be projected on a screen from the PC, for small classes or for a larger
      audience (200 persons). Its development as an interactive multimedia program is
      in progress and will soon be available on the Internet.

PMID- 8740163
TI  - Interaction of lectins with their ligand carbohydrate of alpha-fetoprotein:
      analysis by mixed-lectin affinity electrophoresis.
AB  - Serum or ascites alpha-fetoprotein (AFP) from patients with hepatocellular
      carcinoma and from a cord blood were analyzed by affinity electrophoresis with
      two lectins mixed in agarose gel in a combination of concanavalin A (Con A) and
      Lens culinaris agglutinin A (LCA-A) or of erythroagglutinating phytohemagglutinin
      (E-PHA) and Allomyrina dichotoma lectin (allo A). Con A- and LCA-A-reactive AFP
      C2-L3 was not further retarded by mixing with either of the other lectin. It
      showed a mobility identical with that of AFP-C2 or AFP-L3. E-PHA- and allo A
      reactive AFP-P4-A3 showed similar results. It migrated with intermediate
      mobilities of AFP-P4 and AFP-A3 depending on the concentrations of the two
      lectins mixed in the gel. The results indicate that the two mixed lectins compete
      with each other for the topologically different lectin-binding sites on the
      oligosaccharide of AFP molecule.

PMID- 8740164
TI  - Immobilized metal ion affinity gel electrophoresis: quantification of protein
      affinity to transition metal chelates.
AB  - This paper describes some recent advances in the methodology of immobilized metal
      ion affinity gel electrophoresis. Four different ways to incorporate metal
      chelate ligands in agarose and polyacrylamide-based electrophoresis gels are
      evaluated, a new polymerizable metal chelating ligand, allyl-2-hydroxy-3-(N,N
      dicarboxymethyl)amino-propyl ether, is introduced, and the determination of
      affinity constants described. The affinities of model proteins (ribonucleases A
      and B and cytochromes c from different species) for the transition metal chelate
      iminodiacetic acid-Cu(II) were studied. The results were found to be in agreement
      with literature data on immobilized metal ion affinity chromatography, and the
      polymer nature and the different chemistries used influenced the affinity only
      quantitatively, keeping the basic mechanisms of interaction unchanged.

PMID- 8740165
TI  - Determination of the number of cysteine residues in high molecular weight
      subunits of wheat glutenin.
AB  - A simple method allowing the determination of the number of cysteine residues of
      the high molecular weight glutenin subunits (HMW-GS) is presented. The method was
      adapted from that of Creighton (T. E. Creighton, Nature 1980, 2840, 487-489) with
      modified reagents for alkylation of the cysteine residues and the electrophoretic
      system. The acid-urea-polyacrylamide gel electrophoresis (PAGE) method, developed
      by Morel (M. H. Morel, Cereal Chem. 1994, 713, 238-242), was adopted and mixtures
      of iodoacetic acid and 4-vinylpyridine were used to alkylate the glutenin
      subunits. The accuracy of the method was checked with some HMW-GS whose number of
      cysteine residues was already known from molecular biology approaches. In
      subunits 5*, 2.2, 2.2* and 4.1 (of Dx types) from cultivars Ben and Fiorello, MG
      7249, MG 315, and Kador, respectively, only 4 cysteine residues were
      demonstrated. Subunit 20 was found to exist as a regular Bx and By subunit pair,
      with the Bx subunit containing only 2 cysteine residues, which is unusual.

PMID- 8740166
TI  - Identification of glycosylated forms of wheat storage proteins using two
      dimensional electrophoresis and blotting.
AB  - Two-dimensional electrophoresis with acid-polyacrylamide gel electrophoresis
      (PAGE), followed by sodium dodecyl sulfate (SDS)-PAGE and SDS-PAGE of unreduced
      polypeptides followed by SDS-PAGE under reducing conditions, were used to
      separate and identify the different subgroups of gliadins and glutenins and to
      distinguish between covalent and noncovalent polymers of glutenins. Gels were
      blotted under semidry conditions according to Lauriere (Anal. Biochem. 1993, 212,
      206-211) to allow large polymers of glutenins to be transferred efficiently.
      Glycosylated polypeptides were detected on blots using either the method of
      Haselbeck and Hosel (Glycoconjugate J. 1990, 7, 63-74), or using anti-(xylose
      containing N-glycan) antibodies (Lauriere et al., Plant Physiol 1989, 90, 1182
      1188). High and low molecular weight glutenin subunits were shown to aggregate
      through both disulfide bridges and noncovalent protein-to-protein interactions.
      Aggregated gamma-gliadins were also demonstrated. Glycans were detected on both
      gliadin and glutenin polypeptides. Covalently aggregated low molecular weight
      glutenins were shown to contain N-glycans with xylose, which demonstrated their
      sorting in the Golgi apparatus.

PMID- 8740167
TI  - State of the art of large-scale genetic purity testing of hybrid vegetable seeds
      using isoelectric focusing at PetoSluis.
AB  - During the past ten years we have been engaged in developing and applying
      isoelectric focusing techniques to test the genetic quality of vegetable seeds.
      We started with isoelectric focusing using carrier ampholytes (IEF-CA), and
      continued research with isoelectric focusing in immobilized pH gradients (IEF
      IPG) and two-dimensional electrophoresis (IPG-DALT). In addition, we have
      developed equipment and procedures for large-scale seed and seedling
      homogenization, sample preparation and semi-automatic gel staining. Moreover, we
      have optimized the sample application and gel running setup for large-scale
      analysis. We have developed hybrid purity (inbred) testing methods for all
      important vegetables, e.g., melon, cole crops, tomato, pepper, watermelon,
      squash, cucumber, radish etc. using either IEF-CA or IEF-IPG of seed or seedling
      proteins, followed by specific or general protein staining. To indicate the
      efficiency of the equipment and procedures developed we present results of two of
      our hybrid purity test methods, namely for brassica using polymorphism for
      phosphoglucomutase (PGM) from dry seeds, and for tomato using polymorphism for
      alcohol dehydrogenase (ADH) from imbibed seeds. We show that one person can
      routinely analyze 1536 individual seeds per day at a cost of about US +0.11 per
      seed for chemicals, materials, and electrophoresis equipment.

PMID- 8740168
TI  - Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of human parotid
      salivary proteins: comparison of dansylation, coomassie blue R-250 and silver
      detection methods.
AB  - Detection of human parotid salivary proteins by dansylation and UV
      transillumination after sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE) has been compared with Coomassie Blue R-250 and silver
      staining procedures. Dansylation gives superior results in terms of both
      resolution and sensitivity, especially with basic proline-rich proteins (PRPs).

PMID- 8740169
TI  - Electrophoretic fingerprinting and multiparameter analysis of cells and
      particles.
AB  - A recently developed electrophoretic instrumentation based on a real-time image
      processing system has been applied to electrophoretic fingerprinting and
      multiparameter analysis of cells and other particles. The comparison between
      theoretical and experimental electrophoretic fingerprints, completed by the
      analysis of differences between measured fingerprints, offers a new methodology
      for better understanding and controlling of the processes at solid/liquid
      interfaces. Moreover, the multi-parameter analysis including electrophoretic
      mobility, size, density and shape of cells can complete the diagnosis and
      prognosis of diseases.

PMID- 8740170
TI  - Quantitation of polymerase chain reaction-amplified DNA fragments by capillary
      electrophoresis and laser-induced fluorescence detection.
AB  - Quantitation of DNA fragments amplified by polymerase chain reaction (PCR) is
      needed for the determination of target DNA in molecular biology. Capillary
      electrophoresis in entangled polymer solution coupled to laser-induced
      fluorescence detection was assessed as an alternative technique to conventional
      slab gel methods to monitor competitive PCR, which consists of amplifying an
      internal standard fragment under the same conditions as the target fragment. The
      fluorescence signal was generated either through end-labeling of the fragments
      using 5'-fluorescein-labeled primers or through intercalation of ethidium bromide
      along the double strand. It is shown that the more accurate and reliable results
      were obtained using this latter pathway.

PMID- 8740171
TI  - Characterization of natural peptides from bovine tissue using capillary
      electrophoresis, high performance liquid chromatography, matrix-assisted laser
      desorption ionization, and Edman degradation.
AB  - A combination of high performance liquid chromatography (HPLC) and capillary
      electrophoresis (CE) spiking, Edman degradation, amino acid analysis and matrix
      assisted laser desorption ionization mass spectrometry (MALDI-MS) was applied for
      the analysis of the primary structure of beta-thymosins. CE has been used to
      resolve peaks which coelute on HPLC, as well as to help establish the identity of
      tryptic fragments in the peptide mapping experiments of the two highly homologous
      beta-thymosins.

PMID- 8740172
TI  - High-speed separation of subnanomolar concentrations of noradrenaline and
      dopamine using capillary zone electrophoresis with laser-induced fluorescence
      detection.
AB  - Capillary zone electrophoresis with laser-induced fluorescence detection has been
      shown to give rapid separations with high resolution and sensitivity. These
      advantages are documented for catecholamines analysis in the present work, which
      shows that separation of subnanomolar concentrations of dopamine and
      noradrenaline (detection limits of 8.6 x 10(-11) M, corresponding to a detected
      amount of 143 zeptomoles of each catecholamine) can be performed in 82 s with an
      efficiency of several million theoretical plates.

PMID- 8740173
TI  - Sodium chloride in preparative free-flow cell electrophoresis: recent
      developments.
AB  - Three buffer systems for free-flow electrophoresis have been designed, which
      proved useful for performing cell electrophoresis in the presence of 50 mM NaCl.
      Each system consists of one central cell suspension buffer with 50 mM NaCl, two
      margin buffers, and two electrode buffers. With the aid of a bromophenol
      blue/maxilon blue accumulation test the various buffers were adjusted to ensure a
      laminar flow and remain unchanged on their way through an electrophoresis
      chamber.

PMID- 8740174
TI  - Electrophoretic and isoelectric focusing analysis of human recombinant alpha 2-HS
      glycoprotein produced in insect cells: analysis of the post-translational events.
AB  - Alpha 2-HS glycoprotein (AHSG) is a human serum glycoprotein synthesized by liver
      cells. It is a natural inhibitor of the insulin receptor tyrosine kinase
      activity. We produced this protein in insect cells by using a recombinant
      baculovirus expressing the whole coding sequence of the protein. By analyzing
      AHSG on isoelectric focusing and on sodium dodecyl sulfate (SDS) gels, followed
      by immunoblot, AHSG produced in insect cells was found to be phosphorylated and
      to possess the connecting peptide between the A and the B chains. The same
      features were found in the protein produced by Hep3B, a human liver cell line
      that synthesizes AHSG. By contrast, no phosphorylation could be detected in AHSG
      present in normal human plasma, and the connecting peptide was clipped. As the
      protein produced in insect cells is active on insulin receptors, in contrast to
      the plasma protein, our results suggest that the biological activity of the
      protein may be associated with its single chain form together with its
      phosphorylation.

PMID- 8740175
TI  - Immunoglobulin G galactosylation deficiency determined by isoelectric focusing
      and lectin affinoblotting in differential diagnosis of rheumatoid arthritis.
AB  - IgG galactosylation deficiency in patients with rheumatoid arthritis (RA) can be
      detected by isoelectric focusing (IEF)/lectin affinoblotting. We analyzed IgG
      glycosylation in patients with early arthritis (n = 50) and healthy controls in
      order to determine the clinical value of this parameter in differential diagnosis
      of RA. A significant correlation between the IgG galactosylation defect at
      disease onset and the diagnosis of RA during the follow-up was observed.
      Involvement of other clinical parameters (erythrocyte sedimentation rate, C
      reactive protein, rheumatoid factor) did not improve the predictive value of IgG
      galactosylation changes.

PMID- 8740176
TI  - Phenotyping of esterase D and acid phosphatase by rapid isoelectric focusing on
      PhastSystem.
AB  - A rapid isoelectric focusing method on PhastSystem was applied to investigate the
      distribution of esterase D (ESD) and acid phosphatase (ACP) phenotypes in 152 and
      112 unrelated healthy donors, respectively, from the Han population in Beijing.
      Laboratory-made gels with a pH range of 5.0-7.0 and 5.0-8.0 were used for
      analysis of ESD and ACP, respectively, with 1 microliter sample loading. The
      running time was 30-40 min. Gene frequencies for ESD were 0.6809 for ESD*1 and
      0.3191 for ESD*2, (sigma chi 2 = 0.8586 and P > or = 0.50); gene frequencies of
      ACP were 0.2009 for ACP*A, 0.7991 for ACP*B, (sigma chi 2 = 1.7892 and P > 0.20),
      with good agreement between the observed and the expected values.

PMID- 8740177
TI  - Subtyping of group-specific component and protease inhibitor by rapid isoelectric
      focusing on PhastSystem.
AB  - A rapid method on PhastSystem was used to investigate the distribution of group
      specific component (GC) and protease inhibitor (PI) subtypes and their gene
      frequencies from 190 unrelated healthy donors of the Han population in Beijing.
      Laboratory-made gels (pH 4.5-5.4 and pH 4.2-4.9) were used for analysis of GC and
      PI, respectively. Sample loading was 1.5 microliters. The separation and
      visualization time was 0.5 h in each. Gene frequencies were as follows: GC*1F =
      0.4891, GC*1S = 0.2432, GC*2 = 0.2678; rare GC variants were discovered in seven
      cases. The results for PI were: PI*M1 = 0.7542, PI*M2 = 0.1808, PM*M3 = 0.0650.
      Good agreement between the observed and expected values in both GC and PI
      subtyping (for GC, sigma chi 2 = 1.4043, 0.7 < P < 0.8; for PI, sigma chi 2 =
      1.1233, 0.7 < P < 0.8) was obtained.

PMID- 8740178
TI  - Federated two-dimensional electrophoresis database: a simple means of publishing
      two-dimensional electrophoresis data.
AB  - While a two-dimensional electrophoresis (2-DE) database is a relatively old
      concept, in recent years it generated renewed interest within the 2-DE community
      due to two main factors: (i) The high reproducibility of the current 2-DE method
      allows 2-DE images to be exchanged and compared between laboratories. (ii) The
      recent development of faster and more powerful techniques for protein
      identification such as microsequencing, matrix-assisted laser desorption
      ionization-mass spectrometry (MALDI-MS) and amino acid composition makes the
      production of reference protein maps and 2-DE databases cost- and time-effective.
      Additionally, the Internet network's current increase in popularity, combined
      with the rapid growth of Internet-connected laboratories, provides a
      straightforward means of publishing and sharing 2-DE data. While a small number
      of laboratories have already successfully published their data over the net, the
      increasing number of 2-DE database servers that are currently being set up will
      sooner or later require some kind of standardization. Unfortunately,
      standardization can be a long and cumbersome process inevitably leading to
      undesirable compromises. A federated database offers a simple and efficient way
      to publish and share 2-DE data without the need for standardization. Taking
      advantage of Internet protocols such as World Wide Web, they allow each
      laboratory to maintain their own database and to interconnect it with other
      similar databases through the use of active cross-references. This paper first
      presents guidelines for building a federated 2-DE database that may easily be
      followed by most laboratories. It then briefly reviews the state-of-the-art in
      networked 2-DE databases, and finally describes the SWISS-2DPAGE database which
      fully implements the concept of a federated 2-DE database.

PMID- 8740179
TI  - Two-dimensional gel electrophoresis of Escherichia coli homogenates: the
      Escherichia coli SWISS-2DPAGE database.
AB  - Numerous Escherichia coli proteins have already been characterized by two
      dimensional gel electrophoresis (2-D PAGE), using carrier ampholytes in the first
      dimension (VanBogelen, R. A., Sankar, P., Clark, R. L., Bogan, J. A. and
      Neidhardt, F. C., Electrophoresis 1992, 13, 1014-1054). We present here a
      reference protein map of E. coli obtained with immobilized pH gradients (IPG) and
      available in a SWISS-2DPAGE format. Out of the protein spots identified in the E.
      coli gene protein database by Neidhardt's group, 153 have been identified in the
      E. coli gene protein database by Neihardt's group, 153 have been identified on
      the E. coli SWISS-2DPAGE database map by gel comparison and most of them were
      confirmed either by the analysis of amino acid composition (AAC) and/or N
      terminal microsequencing. Additionally, five as yet unsequenced proteins were
      found. The E. coli SWISS-2DPAGE database is part of the ExPASy molecular biology
      server accessible through the Word Wide Web network.

PMID- 8740180
TI  - The yeast SWISS-2DPAGE database.
AB  - The systematic sequencing of the yeast genome will soon be completed. A new
      challenge has been launched by the EUROFAN (European Functional Analysis) project
      whose goal is to elucidate the physiological and biochemical function of newly
      discovered open reading frames (ORF) from yeast. One of the approaches is to use
      protein-based technologies such as two-dimensional gel electrophoresis and
      protein identification in order to establish a yeast reference map. Modified
      protein patterns can be compared to the reference map which hopefully will help
      identify changes related, for example, to growth processes or developmental
      events. This paper describes the yeast SWISS-2DPAGE database in which charge
      separation was obtained using immobilized pH gradient (IPG). Proteins identified
      by gel comparison, amino acid composition analysis and/or microsequencing are
      recorded and described in an accessible uniform format. We have identified more
      than one hundred polypeptides, several of which were newly mapped. In addition,
      the yeast SWISS-2DPAGE database can be freely accessed through the World Wide Web
      (WWW) network on the ExPASy molecular biology server.

PMID- 8740181
TI  - A World Wide Web (WWW) server database engine for an organelle database, MitoDat.
AB  - We describe a simple database search engine "dbEngine" which may be used to
      quickly create a searchable database on a World Wide Web (WWW) server. Data may
      be prepared from spreadsheet programs (such as Excel, etc.) or from tables
      exported from relationship database systems. This Common Gateway Interface (CGI
      BIN) program is used with a WWW server such as available commercially, or from
      National Center for Supercomputer Algorithms (NCSA) or CERN. Its capabilities
      include: (i) searching records by combinations of terms connected with ANDs or
      ORs; (ii) returning search results as hypertext links to other WWW database
      servers; (iii) mapping lists of literature reference identifiers to the full
      references; (iv) creating bidirectional hypertext links between pictures and the
      database. DbEngine has been used to support the MitoDat database (Mendelian and
      non-Mendelian inheritance associated with the Mitochondrion) on the WWW.

PMID- 8740182
TI  - Identification of proteins by their amino acid composition: an evaluation of the
      method.
AB  - Expression of different genomes can be studied by high-resolution two-dimensional
      electrophoresis (2-D PAGE). To help these studies, two-dimensional reference maps
      of different biological tissues and fluids have been built and can be found in
      the SWISS-2DPAGE database, accessible via the World Wide Web network on the
      ExPASy molecular biology server. Different techniques were used to identify the
      polypeptides. At the present time, the method considered to be the fastest and
      the most cost-effective is amino acid composition analysis (AAC). Proteins,
      transferred onto polyvinylidene (PVDF) membranes, were submitted to vapor-phase
      hydrolysis, derivatized with 9-fluorenylmethyl chloroformate (FMOC) and separated
      on an ODS-Hypersil column. Identification was obtained by using the program
      'AACompIdent' available from ExPASy. In this work, different experimental
      parameters, such as contamination, reproducibility and accuracy, have been
      assessed. First, it has been found that a major source of contamination was human
      keratin. Next, amino acids have been classified into 'reliable' and
      'nonreliable'. Accordingly, 'bias' and 'weights' were defined for each amino
      acid, which could be set in the 'AACompIdent' program. Finally, examples of
      identification, including the use of Edman degradation sequence tagging, are
      described.

PMID- 8740183
TI  - Characterisation of proteins from two-dimensional electrophoresis gels by matrix
      assisted laser desorption mass spectrometry and amino acid compositional
      analysis.
AB  - Amino acid compositional analysis and peptide mass fingerprinting by matrix
      assisted laser desorption mass spectrometry have been used to characterise
      proteins obtained from two-dimensional electrophoresis (2-DE) separations of
      human cardiac proteins. A group of twelve protein spots was selected for
      analysis. The identities of eight of the proteins had been determined by
      conventional protein characterisation methods, two were unknown proteins and two
      had putative identities from protein database spot comparison. Amino acid
      analysis and peptide mass fingerprinting gave corresponding identities for seven
      of the twelve proteins, which also agreed with our initial identifications. Three
      proteins which had been identified previously were not confirmed in this study
      and putative identities were obtained for the two unknown proteins. The
      advantages, problems and use of amino acid analysis and peptide mass
      fingerprinting for the analysis of proteins from 2-DE are discussed. The data
      highlight the need to use orthogonal techniques for the unequivocal
      identification of proteins from 2-DE gels.

PMID- 8740184
TI  - Identification of human myocardial proteins separated by two-dimensional
      electrophoresis with matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - Disease-associated proteins separated by two-dimensional electrophoresis (2-DE)
      are often in the femtomole range. Identification of 2-DE separated proteins by
      sequencing and amino acid analysis is limited to the lower picomole range.
      Identification down to the femtomole range can be achieved by matrix-assisted
      laser desorption ionization-mass spectrometry (MALDI-MS). We optimized the
      measurement by MALDI-MS for the analysis of proteolytic digests of 2-DE-separated
      proteins. The direct analysis of peptide mixtures can be used for rapid and
      sensitive protein identification. In some cases, more information about the
      protein can be obtained by separating the peptides by micro high-performance
      liquid chromatography (HPLC) before employing MALDI-MS analysis. More peptides
      are found than in the mixtures, and comparison of HPLC patterns can reveal some
      differences to be post-translational modifications of proteins, even in the case
      of identical peptide mass fingerprints. Furthermore, carboxy-terminal sequencing
      by on-target carboxypeptidase P digestion can be used to confirm the obtained
      result without the need for more material. The search program FRAGFIT was
      modified and renamed FRAGMOD to include the modifications of methionine and
      tryptophan oxidation and alkylation of cysteine by acrylamide into the mass
      search. By applying this procedure, 15 proteins were identified, among them two
      different putative phosphorylated forms of two proteins, a putative N-terminal
      blocking group and four dilated cardiomyopathy-associated proteins. The resulting
      approach for the identification may be used for large-scale investigations of 2
      DE-separated proteins.

PMID- 8740185
TI  - Identification of different galectins by immunoblotting after two-dimensional
      polyacrylamide get electrophoresis with immobilized pH gradients.
AB  - Vertebrate soluble beta-galactoside-binding lectins form a growing protein family
      that recently have been named galectins. Seven different galectins have been
      sequenced and characterized in mammals, and there is compelling evidence for the
      existence of other members of this lectin family. Three among six galectins are
      homodimers with (i) an identical subunit of a relative molecular mass of about
      14500, and (ii) amino acid sequence homologies giving rise to possible
      immunochemical cross-reactivities. They are indistinguishable from each other by
      conventional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE), even when followed by immunoblotting. However, their different isoelectric
      points allow their identification using isoelectric focusing and two-dimensional
      (2-D) polyacrylamide gel electrophoresis. A strategy was developed to identify
      these galectins in crude extracts from cells and tissues, based on the two
      dimensional electrophoresis with immobilized pH gradient (IPG-Dalt) analysis of
      the specific spots of purified galectins and of the spots of crude extracts,
      after silver staining. In addition, 2-D immunoblotting using anti-galectin 1 (Gal
      1) and anti carbohydrate-binding protein 15 (CPB15) antibodies were performed on
      brain and leukemia cells (HL60) allowing an identification of related
      polypeptides. Our results indicate that the use of IPG-Dalt provides a suitable
      reproducibility and allows the detection of galectins or other galactoside
      binding proteins even at basic pIs.

PMID- 8740186
TI  - Plasma protein adsorption patterns on liposomes: establishment of analytical
      procedure.
AB  - After intravenous (i.v.) injection, colloidal drug carriers such as liposomes,
      emulsions, polymeric or solid lipid nanoparticles immediately interact with
      plasma proteins. The adsorbed plasma protein patterns depend on physico-chemical
      characteristics of the carriers' surface and are regarded as a key factor for the
      in vivo behavior of the carriers. The comprehension of the correlation between
      protein adsorption and in vivo organ distribution can be utilized to obtain drug
      targeting to different tissues. Carriers with different protein adsorption
      patterns will interact with different tissue-specific receptors or will be
      recognized by different macrophage subpopulations. Two-dimensional polyacrylamide
      gel electrophoresis (2-D PAGE) was applied to determine the protein adsorption
      patterns on polystyrene particles as model carriers. To transfer this analytical
      method to i.v. injectable colloidal carriers such as liposomes, a new sample
      preparation method was developed. The separation of liposomes from plasma after
      incubation was achieved by gel filtration using a Sepharose 2B column. This
      technique allowed a mild separation independent from eluent composition and only
      according to size differences. Possible protein desorption from the liposomes and
      adsorption onto the gel were minimized by using an eluent with a sufficiently
      high ionic strength. To estimate the efficiency of separation, the content of
      liposomes and plasma in each fraction being eluted was determined by ultraviolet
      (UV) spectroscopy. With this new separation method plasma protein adsorption
      patterns on liposomes could be analyzed for the first time. The sample
      preparation by gel filtration seemed to have no influence on liposome stability
      as far as size distribution is concerned.

PMID- 8740187
TI  - Two-dimensional electrophoretic patterns of acute-phase human serum proteins in
      the course of bacterial and viral diseases.
AB  - Acute-phase serum proteins were analyzed by two-dimensional electrophoresis with
      isoelectric focusing in 3-10 immobilized pH gradients. Most spots were identified
      by reference to the plasma map in the SWISS-2DPAGE database. Serum amyloid A
      protein spots were identified by immunoblotting with specific antiserum and by
      matching determined with predicted values of electrophoretic parameters. Changes
      in the concentrations of alpha 1-antitrypsin, leucine-rich glycoprotein,
      haptoglobin, serum retinol-binding protein and transthyretin were quantitated by
      densitometry of silver-stained gels. Electrophoretic patterns from 18 patients
      with bacterial diseases and 16 patients with viral diseases were compared. The
      incidence of serum amyloid A protein spots was 18/18 in bacterial diseases and
      6/16 in viral diseases. As the the other reactants studied, variations were
      simultaneous in bacterial disease and tended to be staggered in viral diseases.

PMID- 8740188
TI  - Electrophoretic analysis of biliary proteins: application of high resolution two
      dimensional polyacrylamide gel electrophoresis with immobilized pH gradient in
      the first dimension.
AB  - Native bile samples, dialyzed against double distilled water, fractionated by
      Sepharose 2B column chromatography, concentrated by ultrafiltration and
      lyophilized, were solubilized in lysis buffer and studied by two-dimensional
      electrophoresis (2-DE) with immobilized pH gradients in the first dimension. We
      counted 70, and 7 spots in 2-DE patterns of bile from patients with cholesterol
      gallstones and pigment gallstones, respectively.

PMID- 8740189
TI  - The role of diabetic neuropathy and high plantar pressures in the pathogenesis of
      foot ulceration.
AB  - Diabetic foot ulceration is currently a serious medical problem and has,
      therefore, attracted much research attention during the last two decades.
      Previous foot ulceration, diabetic neuropathy, limited joint mobility, high
      plantar pressures, microangiopathy, macroangiopathy and diabetic nephropathy have
      already been identified as risk factors for future foot ulceration. Neuropathy
      has clearly been shown to be an essential permissive factor in the development of
      ulceration in the non-ischaemic foot. Moreover, the pathogenetic role of high
      plantar pressures is crucial in the presence of established clinical neuropathy.
      Nowadays, our therapeutic efforts clearly aim to prevent than treat foot ulcers.
      This demands specialist and team work in the setting up of a diabetic foot clinic
      in an attempt to identify and educate the diabetic patients at risk and, where
      possible to use suitable plantar pressure-reducing systems (footwear, hosiery
      etc.). Then only would it be reasonable to postulate that a significant reduction
      in amputations of diabetic aetiology could be achieved in the near future.

PMID- 8740190
TI  - The effect of inhibiting fatty acid oxidation on basal glucose metabolism in
      Psammomys obesus.
AB  - We administered etomoxir (an inhibitor of fatty acid oxidation) for five days at
      a dose of 50 mg/kg/day to three groups of Psammomys obesus. Group A were
      normoglycemic and normoinsulinemic, group B were normoglycemic and
      hyperinsulinemic, and group C were hyperglycemic and hyperinsulinemic. When
      compared with group A, the hyperglycemic/hyperinsulinemic rats of group C had
      elevated hepatic glucose production (HPG) and elevated glucose uptake (Rg) in all
      tissues measured reaching statistical significance in white gastrocnemius, soleus
      and diaphragm. Five days of etomoxir treatment reduced the plasma glucose levels
      of group C. Etomoxir treatment reduced HGP and although the change was not
      significant, it was supported by significant reductions of Rg in several tissues
      including diaphragm, heart, small intestine, brain and white adipose tissue. Five
      days of etomoxir treatment also reduced the plasma insulin levels in group B and
      group C, when compared to the levels before treatment. These results demonstrate
      that inhibition of fatty acid oxidation significantly reduced hyperglycemia,
      hyperinsulinemia and Rg in some tissues in group C animals suggesting that
      elevated levels of fatty acid oxidation and increased glucose turnover may be
      associated with development of NIDDM in Psammomys obesus.

PMID- 8740191
TI  - Effects of tamoxifen on serum prolactin levels, pituitary immunoreactive
      prolactin cells and uterine growth in estradiol-treated ovariectomized rats.
AB  - Pituitary effects of the antiestrogen tamoxifen are not well established,
      although estrogen is known to have a stimulatory role in prolactin secretion.
      Effects of tamoxifen on serum prolactin levels, pituitary wet weight and number
      of prolactin cells were studied. Ovariectomized female Wistar rats were injected,
      subcutaneously, with estradiol valerate, 50 or 300 micrograms/rat per week for 2
      or 10 weeks. Tamoxifen was injected during the last days of estrogen treatment.
      Data were compared with two other groups, treated with estradiol valerate alone
      or estradiol valerate plus the dopamine agonist bromocriptine. Serum prolactin
      levels were increased by estrogen treatment with all doses used. Furthermore,
      rats treated with 300 micrograms of estradiol valerate, for 2 and 10 weeks,
      showed a clear increase in pituitary weight and number of prolactin cells (p <
      0.05). Bromocriptine decreased prolactin levels, pituitary weight and the number
      of prolactin cells (p < 0.05). Tamoxifen associated to subacute period of
      estrogen administration resulted in a significant reduction of serum prolactin
      levels and pituitary weight (p < 0.05). No effects on prolactin levels or number
      of prolatin cells were observed with tamoxifen associated to chronic estrogen
      treatment. Tamoxifen also presented a dose-related inhibitory effect upon
      estrogen-stimulated rises in uterine weight and DNA content. In conclusion, the
      results of the present paper showed that tamoxifen reduced estrogen-stimulated
      prolactin levels in some, but not in other hormonal conditions and that these
      effects were not mediated by an inhibition of lactotroph cell growth. Further
      studies are needed to define the exact role of antiestrogens at molecular level
      in hyperprolactinemic states and their eventual connection with dopamine and its
      agonists.

PMID- 8740192
TI  - Ultrastructural dynamics of mitochondrial morphology in varying functional forms
      of human adrenal cortical adenoma.
AB  - Adrenal cortical mitochondria display an extensive capacity to adapt
      morphologically to the functional state of the adrenal cortical cell. In the
      present study, we have used transmission electron microscopy to analyze cortical
      tissues from 3 normal human adrenal glands (zona fasciculata and zona
      glomerulosa), and from 8 steroid-secreting adrenal cortical adenomas (3 cortisol
      producing, 4 aldosterone-producing, and 1 progesterone-producing tumor),
      correlating both clinical and biochemical features with cellular ultrastructure.
      The morphology of mitochondria was related to the enzyme activity and steroid
      biosynthetic capacity of each tumor. Cells from aldosterone-producing adenomas
      demonstrated a large number of elongated tubular mitochondria with characteristic
      bridging of inner membranes, producing a lamellar-type pattern. Cells from
      cortisol-producing adenomas showed large round mitochondria with vesicular or
      tubulovesicular inner membranes surrounded by a characteristic dilated smooth
      endoplasmic reticulum. A highly unusual progesterone-producing adenoma, in which
      a deficiency of 21 alpha-hydroxylase activity was demonstrated, showed a peculiar
      type of enlarged lamellar mitochondria with bright inner matrix and a reduced
      number of inner membranes. Therefore, the ultrastructural characteristics of
      adrenal cortical mitochondria appear to be potential markers for the
      differentiation of steroid-producing adenomas. These studies point to the
      possibility of a broader use of electron microscopy in the study of adrenal
      tumors.

PMID- 8740193
TI  - Resistance to natriuresis in patients with peritonitis carcinomatosa.
AB  - The natriuretic effect of atrial natriuretic peptide (ANP) is blunted in certain
      clinical disorders such as congestive heart failure and liver cirrhosis, despite
      the elevated plasma ANP levels. These sodium-retaining states are characterized
      by increased activity of the renal sympathetic nerves. Recent studies have shown
      higher levels of circulating and urinary catecholamines in cancer patients. We
      hypothesized that the increased adrenergic activity may be responsible for
      ascites formation in patients with peritonitis carcinomatosa (PC). The objective
      of this study was to determine the renal responses to endogenous ANP in patients
      with PC. Patients, hospitalized at our institute for PC, were examined using
      renal clearance studies for 2 h. Non-cancer patients were also examined as
      control subjects. Statistical analysis was performed using Wilcoxon's rank sum
      test. The results showed that absolute and fractional sodium excretions were
      markedly lower in patients with PC (54 +/- 16 microEq/min, means +/- SE, p <
      0.0005; 0.55 +/- 0.15%, p < 0.005) than in control patients (166 +/- 14
      microEql/min; 1.14 +/- 0.09%, respectively). Plasma ANP concentration was
      increased in patients with PC (34.7 +/- 8.4 pg/ml, p < 0.001) in comparison with
      control patients (13.3 +/- 2.0 pg/ml). Plasma and urinary levels of
      norepinephrine were significantly higher in cancer patients (0.36 +/- 0.10 ng/ml,
      p < 0.05; 125 +/- 20 ng/dl GF, p < 0.05) than in the controls (0.17 +/- 0.02
      ng/ml; 73 +/- 13 ng/dl GF). These results suggest that increased renal
      sympathetic nerve activity may contribute to the attenuation of the natriuretic
      effect of ANP in patients with PC.

PMID- 8740194
TI  - Effect of surgically induced hypoestrinism on immunoregulation in perimenopausal
      women.
AB  - The object of the present study was to investigate the effect of bilateral
      oophorectomy (OOX) on CD4+ and CD8+ subsets of T-lymphocytes in 8 immunologically
      healthy perimenopausal women with regular bleeding. Between the 12th and 16th
      week after OOX, CD8+ (%) increased in all of the investigated women (mean values
      compared to values before OOX: 37.8 +/- 3.4 vs 26 +/- 4.13, p < 0.05). CD4+
      increased in five women, and decreased in another three (means: 36.4 +/- 3.6 vs
      38 +/- 4.6). The immunoregulatory index (CD4+/CD8+ ratio) declined in seven
      women, while it was unchanged in one (means: 1.09 +/- 0.2 vs 1.71 +/- 0.22, p <
      0.05). The compliance of the treatment was controlled by serum estrogen, LH and
      FSH. From these results it is apparent that surgically induced hypoestrinism
      inhibits immunoregulation in perimenopausal women.

PMID- 8740195
TI  - Serum androsterone levels in children.
AB  - Serum androsterone was measured by radioimmunoassay in 79 girls and 80 boys aged
      between six months to sixteen years. In boys, androsterone levels were found to
      be low until the age of 12 years and then rapidly increased between the ages of
      12-13 years. This increase of serum androsterone in boys seems to be related to
      the rapid increase of testosterone. On the other hand, in girls the androsterone
      levels were found to be low until the age of 10 years. However, from this age
      onwards, although individual values were variable, androsterone levels did not
      increase as rapidly as in boys but rather gradually with age which appeared to be
      influenced by the progressive increase of dehydroepiandrosterone (DHEA) in girls.

PMID- 8740196
TI  - Testicular function in hypercholesterolemic male patients during prolonged
      simvastatin treatment.
AB  - Simvastatin is a very effective hypocholesterolemic drug which, reducing
      cholesterol biosynthesis, can affect normal steroid hormone production. Testes
      require a continuous cholesterol supply for testosterone synthesis and this can
      be derived from low density lipoprotein receptor-mediated uptake or from de novo
      local synthesis. The aim of the study was to see if prolonged simvastatin
      treatment compromised endocrine testicular function both in basal conditions and
      after stimulation by human Chorionic Gonadotropin (hCG) (Profasi 5,000 Ul, i.m.
      at 8 a.m.). Free testosterone (FT) levels were determined at baseline and after
      3, 6 and 12 months of simvastatin treatment (20 mg/day) in eight
      hypercholesterolemic patients. At the same time we performed a hCG stimulation
      test to evaluate testicular reserve. A significant reduction of FT, both basal
      and hCG-stimulated, was observed in the 6th and the 12th month of the study.
      However, FT levels remained in the normal range and no patient complained of
      gonadal function related symptoms. No significant change was observed in
      estradiol response to hCG test. Lastly, there was no variation in LH, FSH,
      progesterone, 17-OH-progesterone, androstenedione or dehydroepiandrosterone
      sulphate levels. Our study concluded that the drug causes a mild decline in FT
      secretion without any clinical sign of testicular dysfunction.

PMID- 8740197
TI  - Diurnal rhythm of plasma insulin and glucose in rats made obese by a high fat
      diet.

PMID- 8740198
TI  - Regulation of lipoprotein lipase activity by growth hormone in differentiated
      adipocytes from sheep.

PMID- 8740199
TI  - Energy metabolism in the hypothalamus and plasma cortisol levels in patients with
      schizophrenia.

PMID- 8740200
TI  - The attenuated inhibitory action of octreotide, a somatostatin analogue on GHRH
      induced growth hormone response in type I diabetes mellitus.

PMID- 8740201
TI  - Influence of dexamethasone and 1,25-Dihydroxyvitamin D on Walker carcinosarcoma
      256 growth and parathyroid hormone-related protein secretion.

PMID- 8740202
TI  - Interactions between medullary and spinal respiratory rhythm generators in the in
      vitro brainstem spinal cord preparation from newborn rats.
AB  - As medullary and spinal respiratory activities coexist in the in vitro brainstem
      spinal cord preparation from newborn rats previously deeply anaesthetized with
      diethyl ether, we sought evidence for reciprocal interactions between the
      medullary and spinal respiratory generators. A descending influence of medullary
      onto spinal respiratory generators has been characterized by the constant onset
      latency of the spinal burst within the corresponding medullary respiratory cycle.
      Non-harmonic (29%) and harmonic (9%) correlations were observed between the two
      phenomena, but correlations could also be low (27%) or absent (35%). Variations
      in the pH or FCO2 of the artificial cerebrospinal fluid were able to induce or
      suppress this medullary control of spinal respiratory activity. An ascending
      relationship between spinal and medullary respiratory generators has been
      revealed as a systematic variation of the medullary period due to resetting.
      Depending on the timing of the spinal respiratory activity, the medullary burst
      could be either advanced through a shortened medullary period, or delayed through
      a lengthened one. In conclusion, it was possible to show the existence of
      reciprocal relationships between the medullary and spinal respiratory generators
      in the in vitro brainstem spinal cord preparation from newborn rats. These
      results are interpreted in relation to the central interactions between
      locomotion and respiration in mammals which occur during rapid propulsion and
      which could be mediated by the spinal respiratory generator.

PMID- 8740203
TI  - The efferent-mediated suppression of otoacoustic emissions in awake guinea pigs
      and its reversible blockage by gentamicin.
AB  - The physiology of the medial efferent olivocochlear system involves suppressive
      interactions of contralateral sounds on ipsilateral sound-evoked responses, but
      its role is largely unknown to date. Medial efferents act at the level of
      cochlear outer hair cells via cholinergic synapses and might affect their
      mechanical activity, thereby modulating auditory sensitivity. The aim of the
      present work was to obtain noninvasive measurements of distortion-product
      otoacoustic emissions (DPOEs), which reflect outer hair cell function, in order
      to establish the characteristics of medial efferent-induced suppression in awake,
      restrained guinea pigs. A clear suppression of DPOEs was induced by continuous
      contralateral white noise presented at 20-70 dB SPL, in the absence of any
      confounding effect of anesthesia, middle-ear muscles, or acoustic cross talk.
      Recently, acute injection of a high dose of the aminoglycoside antibiotic
      gentamicin (150 mg/kg) was reported to alter the suppressive effect of
      contralateral noise on eighth nerve-compound action potentials, presumably by
      blocking efferent synapses to outer hair cells. This hypothesis was confirmed
      with DPOEs for which a single injection of gentamicin at the same dose abolished
      suppression after about 1-2 h, whereas no change in basal levels was observed.
      Complete recovery was obtained after 48 h. This experiment may provide an easy,
      noninvasive tool for studying auditory function with and without functioning
      efferents.

PMID- 8740204
TI  - Circling behaviour induced by apomorphine after lesions of the habenula.
AB  - Apomorphine, 2 mg/kg (s.c.) produced significant contralateral turning in rats
      with unilateral radiofrequency lesions of the habenula nucleus over a test period
      of 60 min when tested at post-surgery days 3, 7, and 14. Levels of contralateral
      circling were not significantly increased when the animals were tested on days 21
      and 28, although a contralateral bias was still observed. Rotation induced by
      apomorphine was completely blocked by the administration of haloperidol (0.3
      mg/kg i.p.), and there was no behavioural asymmetry in lesioned animals following
      administration of saline or a high dose of haloperidol (2 mg/kg i.p.). These
      results indicate that unilateral habenula lesions lead to imbalance of
      dopaminergic activity, which is expressed as contralateral circling when the
      animal is challenged with apomorphine.

PMID- 8740205
TI  - Effects of T-type, L-type, N-type, P-type, and Q-type calcium channel blockers on
      stimulus-induced pre- and postsynaptic calcium fluxes in rat hippocampal slices.
AB  - The contribution of T-, L-, N-, P-, and Q-type Ca2+ channels to pre- and
      postsynaptic Ca2+ entry during stimulus-induced high neuronal activity in area
      CA1 of rat hippocampal slices was investigated by measuring the effect of
      specific blockers on stimulus-induced decreases in extracellular Ca2+
      concentration ([Ca2+]o). [Ca2+]o was measured with ion-selective electrodes in
      stratum radiatum (SR) and stratum pyramidale (SP), while Ca2+ entry into neurons
      was induced with stimulus trains (20 Hz for 10 s) alternately delivered to SR and
      the alveus, respectively. The [Ca2+]o decreases recorded in SR in response to SR
      stimulation represented mainly presynaptic Ca2+ entry (Capre), while [Ca2+]o
      decreases recorded in SP in response to alvear stimulation were predominantly
      based on postsynaptic Ca2+ entry (Capost). Ethosuximide and trimethadione were
      ineffective in concentrations up to 1 mM. At 10 mM, they reduced Capost and, much
      less, also Capre. Nimodipine (25 microM) reduced Capost and, to a minor extent,
      Capre. omega-Agatoxin IVA (0.4-1 microM) and omega-contoxin MVIIC (1 microM) also
      reduced both Capre and Capost, but with a stronger action on Capre. omega
      Conotoxin GVIA (3-8 microM) reduced Capost without effect on Capre. We conclude
      that during stimulus-induced, high-frequency neuronal activity Capost is carried
      by P/Q-, N-, and L- type channels and probably a further channel type different
      from these channels. Capre includes at least P/Q- and possibly L-type channels. N
      type channels did not contribute to Capre in our experiments. Since ethosuximide
      and trimethadione were only effective in high concentrations, their action may be
      unspecific. Thus, T-type channels do not seem to play a major part in Ca2+ entry
      in this situation.

PMID- 8740206
TI  - A comparison of the early development of ischemic brain damage in normoglycemic
      and hyperglycemic rats using magnetic resonance imaging.
AB  - The early evolution of ischemic brain injury under normoglycemic and
      streptozotocin-induced hyperglycemic plasma conditions was studied using magnetic
      resonance imaging (MRI). Male Sprague-Dawley rats were subjected to either
      permanent middle cerebral artery occlusion (MCAO), or 1-h MCAO followed by
      reperfusion using the intraluminal suture insertion method. The animals were
      divided into four groups each with eight rats: normoglycemia with permanent MCAO,
      normoglycemia with 1-h MCAO, hyperglycemia with permanent MCAO, and hyperglycemia
      with 1-h MCAO. Diffusion-weighted images (DWIs) and T2-weighted images (T2WIs)
      were aquired every 1 h from 20 min until 6 h after MCAO, at which time cerebral
      plasma volume images (PVIs) were acquired. Tissue infarction was determined by
      triphenyltetrazolium chloride staining at 7 h after MCAO. The ischemic damage,
      measured as the area of DWI and T2WI hyperintensity and tissue infarction,
      increased significantly in hyperglycemic rats in both permanent and transient
      MCAO models. In the permanent MCAO model, the maximal apparent water diffusion
      coefficient (ADC) decline under either normo- or hyperglycemia was about 40%, but
      the speed of ADC drop was faster in hyperlgycemic rats than in normoglycemic
      rats. Reperfusion after 1 h of MCAO in normoglycemic rats partly reversed the
      decline in ADC, whereas the low ADC area continued to expand after reperfusion in
      the hyperglycemic group. Between the two hyperglycemic groups with either
      permanent MCAO or reperfusion, no significant difference was found in the infarct
      volume measured at 7 h after MCAO. However, reperfusion dramatically increased
      the extent and accelerated the development rate of vasogenic edema. ADC in the
      hyperglycemic reperfusion group also dropped to a lower level. A large "no
      reflow" zone was found in the ischemic hemisphere in the hyperglycemic
      reperfusion group. This study provides strong evidence to support that
      preischemic hyperglycemia exacerbates ischemic damage in both transient and
      permanent MCAO models and demonstrates, using MRI, that reperfusion under
      preischemic hyperglycemia accelerates the evolution of early ischemic injury.

PMID- 8740207
TI  - Effects of cholecystokinin on Y, X, and W cells in the dorsal lateral geniculate
      nucleus of rats.
AB  - The role of the cholecystokinergic input to the rat's dorsal lateral geniculate
      nucleus (dLGN) was studied by examining the effect of iontophoretically
      administered CCK-8S on the neuronal response to stimulation of the receptive
      field center. Peristimulus activity was recorded extracellularly from 108 neurons
      grouped according to the type of receptive field (OFF, ON, or ON-OFF) and
      classified with respect to their Y, X, or W properties by means of discriminant
      analysis. CCK affected the response to a center-sized spot of light in two thirds
      of the neurons investigated. The center response decreased in 50 of 73 CCK
      sensitive neurons (69%), predominantly in Y OFF and X OFF center cells (17 of
      19). In the remaining 23 cells the center response increased, most consistently
      (11 of 17) in W ON center cells. Center and surround responses were similarly
      influenced. Inhibitions and excitations induced by CCK-8S were reproducible, dose
      dependent, and receptor mediated. The CCKB antagonist PD 135158 reduced the CCK
      effects in 10 of 14 cells; the CCKA antagonist KL 1001 reduced the CCK effects in
      17 of 36 cells. The CCK-induced inhibition was B-receptor specific in 4 of 8
      cells, A-receptor specific in 2 of 8 cells, and partially mediated by each of the
      two types of receptor in the remaining 2 cells. Blocking by the CCKA antagonist
      was more frequently observed in W cells than in cells with Y or X
      characteristics. The data show that CCK modifies the activity of dLGN cells in a
      variable direction depending on the specific cell type (Y, X, W) and response
      pattern (OFF, ON). The effects of CCK are discussed in relation to proposed
      functions of the superior collicular input to the dLGN.

PMID- 8740208
TI  - C-Fos expression in trigeminal nucleus neurons after chemical irritation of the
      cornea: reduction by selective blockade of nociceptor chemosensitivity.
AB  - The distribution and number of trigeminal brainstem and higher order sensory
      neurons expressing the protein product of the proto-oncogene c-fos after noxious
      stimulation of the cornea was studied in the rat using immunocytochemistry. The
      possibility that attenuation of nociceptive messages from the cornea by diltiazem
      reduced Fos-like immunoreactivity of spinal trigeminal neurons was also examined.
      A group of animals were killed 2-3 h after corneal stimulation. One cornea was
      stimulated with: a drop of 10 mM acetic acid; with acid plus mechanical
      scratching of the corneal epithelium; or with a drop of saline of 56 degrees C.
      Half of the animals treated with acid had been pretreated ipsilaterally with
      topical diltiazem (10 mM). Control rats received either saline in one eye or no
      treatment. Another group of animals were killed 7-8 h after stimulation with
      acetic acid. Fos-like immunoreactive neurons were counted in serial brainstem
      sections using an anti-Fos primary antiserum and processed according to the
      avidin-biotin complex method. In rats killed 2-3 h after corneal stimulation with
      acid, heat, or acid plus mechanical injury, labelled neurons were found in
      laminae I and II of the intermediate zone between caudalis and interpolaris
      subnuclei of the ipsilateral spinal trigeminal nucleus and, in a reduced number,
      in the symmetrical zones of the contralateral side. In animals stimulated with
      noxious heat or combined mechanical and chemical injury, a few scattered cells
      were also labelled in the ipsilateral junction between the cervical spinal cord
      and the caudalmost part of the trigeminal subnucleus caudalis. In rats killed 7 h
      after stimulation with acid, stained neurons were observed in the same areas of
      the trigeminal nucleus as in rats killed at shorter times, but in lower numbers;
      in these animals, no immunoreactive cells were found in deeper laminae or in
      higher sensory relay nuclei. Pretreatment with diltiazem significantly reduced
      the number of cells of the spinal trigeminal nucleus labelled after corneal
      stimulation with acid. The results indicate that brief noxious stimulation of the
      cornea evoke expression of c-Fos in neurons of the spinal trigeminal complex.
      Diminution by diltiazem of the number of immunoreactive neurons activated by
      corneal irritation suggests that this drug, by reducing chemosensitivity of
      nociceptive terminals, decreases nociceptive inflow to central nervous structures
      involved in ocular pain perception.

PMID- 8740209
TI  - Light and electron microscopic analysis of synaptic input from cortical area 17
      to the lateral posterior nucleus in cats.
AB  - The morphology and synaptic organization of the corticothalamic (CT) fibres from
      area 17 were studied in the lateral posterior nucleus (LP) of the thalamus in
      cats. Injection of the anterograde tracer Phaseolus vulgaris leucoagglutinin
      (PHAL) into primary visual cortex labelled a band of CT fibres in the LP with
      terminal field confined to its lateral division "LP1". PHAL-labelled CT axons in
      the LP1 gave rise to both en passant and terminal boutons. They usually
      established several synaptic contacts--often in complex glomerulus-like synaptic
      arrangements--with dendritic shafts of large diameter and presynaptic dendrites
      containing pleomorphic vesicles. Postsynaptic targets of the PHAL-labelled CT
      boutons were characterized by postembedding gamma-aminobutyric acid (GABA)
      immunocytochemistry. It appeared that, in the LP1 of the cat, almost half (44.5%)
      of the postsynaptic dendrites to CT boutons from area 17 belonged to the GABA
      immunopositive interneurons and the majority (41%) of these GABA-immunopositive
      dendrites were F2 terminals. These results indicate that the CT axons from the
      striate cortex in the LP of the cat, in addition to a direct excitatory action,
      exert a powerful feed-forward inhibition on the thalamic principal cells.

PMID- 8740210
TI  - Extracellular K+ accumulations and synchronous GABA-mediated potentials evoked by
      4-aminopyridine in the adult rat hippocampus.
AB  - Transient changes in extracellular potassium concentration ([K+]o) and field
      potentials were evoked by 4-aminopyridine (4-AP; 50-100 microM) and recorded with
      ion-selective microelectrodes in CA1b, CA3b and dentate sectors of adult rat
      hippocampal slices. Long-lasting field potentials recurred at a frequency of
      approximately 1/60 s (0.016 +/- 0.003 Hz) in association with increases in [K+]o
      which were largest and most sustained in the dendritic regions where afferent
      fibers terminate (dentate > CA1 > CA3) and in the hilus. In stratum radiatum of
      CA1 or stratum moleculare of the dentate these fields had a peak amplitude of 1.4
      +/- 0.29 mV, duration 8.3 +/- 1.6 s, and were accompanied by increases in [K+]o
      of 1.8 +/- 0.22 mM that lasted 32 +/- 5.5 s (n = 17 slices). Interictal
      epilentiform potentials, which were brief (< 0.2 s) and more frequent at
      approximately 1/3 s (0.30 +/- 0.02Hz) were also present in CA1, CA3 and the hilus
      and associated with small increases in [K+]o (< or = 0.5 mM, duration < or = 2
      s). Interictal activity was blocked by 6-cyano-7-nitroquinoxalone-2,3-dione
      (CNQX; 5-20 microM); the slow, less frequent potentials were resistant to both
      CNQX and DL-2-amino-5-phosphonovaleric acid (APV; 50 microM) and reversibly
      blocked (or attenuated by approximately 80%) by bicuculline methiodide (BMI) (25
      100 microM). The BMI-sensitive potentials were also abolished by baclofen (100
      microM), an effect which was reversed by 2-OH-saclofen (100 microM). Focal
      application of KCI or GABA in the absence of 4-AP evoked long-lasting field and
      [K+]o potentials which were similar to those evoked by 4-AP but more sustained.
      The proportional relationship between the amplitudes of field and K+ potentials
      with GABA closely resembled that observed for 4-AP; in contrast the slope of KC1
      evoked responses was lower. Our results demonstrate that in the adult rat
      hippocampus 4-AP induces in many different regions accumulations of [K+]o in
      synchrony with the long-lasting field potentials, which are known to correspond
      to an intracellular long-lasting depolarization of the pyramidal cells. These
      changes are smaller than those which occur in the immature rat hippocampus--which
      may be related to differences in Na-K-ATPase and susceptibility to seizures.
      These events involve the activation of GABAA receptors, are under the modulatory
      control of GABAB receptors, and likely arise from the activity of GABAergic
      interneuron and/or afferent terminals. The long-lasting field potentials appear
      to reflect mainly the direct depolarizing actions of GABA and to much more
      limited extent the associated accumulation of [K+]o.

PMID- 8740211
TI  - Unilateral displacement of lower limb evokes bilateral EMG responses in leg and
      foot muscles in standing humans.
AB  - During upright stance, foot dorsiflexion induced by the movement of a supporting
      platform elicits a short- (SLR) and a medium-latency response (MLR) in both the
      soleus and the flexor digitorum brevis muscles; foot plantarflexion elicits a MLR
      in the tibialis anterior. The SLR is the counterpart of the stretch reflex, but
      no general agreement exists about the origin of the MLR, though recent results
      suggest that it is transmitted through group II afferent fibres. Animal studies
      have shown that group II fibres impinge on interneurones projecting
      contralaterally as well as ipsilaterally, whereas group I fibres impinge on
      interneurones which project mainly ipsilaterally. Therefore, we compared the
      changes in amplitude and latency of the SLRs and MLRs in the right and left limb
      during postural perturbations induced while subjects maintained both feet on the
      platform (both-on condition) or while they maintained only one foot on the
      platform and the other on firm ground (one-on condition). Under the both-on
      condition, the pattern of EMG responses described above occurred bilaterally.
      Under the one-on condition, both SLRs and MLRs occurred in the displaced leg.
      However, whereas the SLRs did not change in amplitude compared with the both-on
      condition, the MLRs decreased in amplitude to about 50%. MLRs were also present
      in the non-displaced leg. They were not preceded by any SLR but showed a further
      decrease in size with respect to the corresponding responses in the perturbed
      leg. Latency of the MLRs of the perturbed leg increased by about 5 ms passing
      from the both-on to the one-on condition. In the latter condition, a further
      increase of 5 ms was observed in the nonperturbed leg with respect to the
      displaced one. The occurrence of the MLRs but not of the SLRs in the
      contralateral non-displaced leg is in keeping with the notion that crossed neural
      pathways fed by spindle group II afferent fibres subserve the MLRs. The changes
      in latency of the MLRs under the one-on condition compared with both-on give a
      cue about the synaptic delays along the neural circuit and the time taken by the
      afferent impulses to cross the spinal cord.

PMID- 8740212
TI  - Thumb-pointing is humans after damage to somatic sensory cortex.
AB  - Three patients with a severe somatosensory deficit consequent on damage of the
      right somatosensory cortices were required, while blindfolded, to point with
      their insensate thumb to select positions on the other left fingers. Given the
      absence of feedback, the motor performance of the insensate thumb appeared
      grossly impaired in all patients. However, all patients attained end-points with
      an accuracy greater than chance. This result suggests that spatial accuracy may
      not rely entirely on sensory feedback. A good accuracy of pointing was evinced
      also in potentially facilitating conditions where somatosensory and motor cues
      coming from the intact side during simultaneous movement of both thumbs, vision
      of stimulated point and final thumb position, and visuomotor imagery were
      available. Furthermore, in one patient, the accuracy of the insensate thumb in
      cued conditions was higher than in a reference baseline condition, thus
      indicating that motor and cognitive cues can help the motor performance of
      patients with cortical somatosensory lesions.

PMID- 8740213
TI  - Fixation and saccade control in an express-saccade maker.
AB  - In express-saccade makers a large incidence of express saccades (latencies around
      100 ms) is paralleled by a reduced ability to suppress saccade generation when
      required. Such a behavior occurs frequently in dyslexics. We studied the
      latencies and the metrical properties of saccades in the very rare case of an
      adult, nondyslexic express-saccade maker (male, age 29 years). The subject
      produced 65-95% express saccades in the gap (fixation point removed 200 ms before
      target onset) as well as in the overlap (fixation point not removed) paradigm,
      which qualified the subject as the most clear case of an express-saccade maker
      found so far. The number of express saccades increased rather than decreased when
      fixation foreperiod, gap duration, and target location were randomized from trial
      to trial as compared to when they remained constant. In the memory-guided saccade
      and in the antisaccade paradigms in which immediate saccade execution to a visual
      target had to be suppressed, the subject often reacted to the target with express
      saccades in an involuntary way. The amplitudes of express saccades were--in some
      conditions--found to progressively decrease with increasing latency, giving rise
      to amplitude transition functions. The present findings disprove the notion that
      express saccades are generated based on the prediction of the time and location
      of target appearance and support the notion that they are the result of an
      optomotor reflex. It is argued that the operation of the reflex is gated by a
      separate fixation system. Express-saccade makers are described as subjects with a
      dysfunction of the fixation system. Recent neurophysiological findings suggest
      that the subject studied in the present study has a selective dysfunction of the
      fixation system at the level of the superior colliculus.

PMID- 8740214
TI  - Response times and handedness in simple reaction-time tasks.
AB  - The anticipatory (preparatory) cerebral events in simple reaction-time tasks may
      depend on the ability of a subject to predict accurately the time of occurrence
      of the stimulus requiring a particular response. In order to examine this
      hypothesis, we recorded cerebral and muscle responses in two different
      conditions, each involving three simple reaction-time tasks. Auditory tones were
      presented either regularly (i.e., predictably) or irregularly and subjects were
      required to respond to each tone with left hand, right hand or both hands in
      different runs. Responses were simultaneously averaged both backward and forward
      from the response (response-synchronized) and forward from the stimulus (stimulus
      synchronized). Response-synchronized cerebral potentials to the regular tones
      were characterized by a slow negative shift, the bereitschaftspotential (BP),
      that began prior to stimulus onset and whose terminal phase was characterized by
      a small, higher frequency, negative shift (HFNS). By contrast, response
      synchronized cerebral potentials to the irregular tones for both groups did not
      contain a BP, but a more conspicuous HFNS that began after stimulus onset. Both
      the response time and the latency of the N1 sensory-related component of the
      cerebral evoked potential recorded in the stimulus-synchronized averages (which
      aligns with HFNS) were delayed in the irregular condition. These findings suggest
      that, for both right- and left-handed subjects, the BP is not required for
      voluntary movement, and that anticipatory cerebral activity, as reflected by the
      BP, represents not only a preparation to make a particular response but also a
      preparation to process the stimulus.

PMID- 8740215
TI  - The effect of lorazepam on the motor cortical excitability in man.
AB  - The effect of the short-acting benzodiazepine lorazepam on motor cortex
      excitability was investigated in 11 healthy volunteers using the technique of
      focal transcranial magnetic stimulation. The threshold intensity for evoking an
      electromyographic response in the resting and active abductor digiti minimi
      muscle, the size of the motor evoked potential, the duration of the cortical and
      peripheral silent periods, the corticocortical inhibition and facilitation after
      paired magnetic stimuli, and the transcallosal inhibition were used as parameters
      to assess various aspects of motor system excitability. Baseline values were
      compared with data obtained 2, 5 and 24 h after a single oral dose of 2.5 mg
      lorazepam. Resting and active motor thresholds and the size of the motor evoked
      potential remained unchanged. The duration of the cortical silent period was
      prolonged with a maximum effect 5 h after drug intake, while the peripheral
      silent period did not show any lengthening at that time. The corticocortical
      inhibition showed a tendency toward more inhibition, while the corticocortical
      facilitation was almost completely suppressed. The transcallosal inhibition
      showed an inconsistent trend to less inhibition. In parallel to the
      pharmacokinetics of lorazepam, all effects peaked at 2 h and 5 h, and were
      (partially) reversible after 24 h. It is hypothesized that most of these findings
      are due to the reinforcement of GABA action by lorazepam at the level of the
      motor cortex. The lack of effect on motor threshold and on the size of the motor
      evoked potential may indicate that these parameters are physiologically distinct
      from corticocortical excitability and the cortical silent period. The relevance
      of the present data in clinical epileptology is discussed.

PMID- 8740216
TI  - Brain activity related to serial cognitive performance resembles circuitry of
      higher order motor control.
AB  - Differences between two states of cerebral activation were studied in eight
      subjects by positron emission tomography (PET) of regional cerebral blood flow
      (rCBF) and subsequent statistical parameter mapping. Subjects had to respond to a
      row of numbers presented on tape. In one condition they had to repeat each
      number. In the other condition the last heard number had to be added to the
      number presented before. Cerebral activity specifically related to the serial
      addition task was distributed over supplementary motor area (SMA), left premotor
      cortex and superior dorsal parietal cortex bilaterally, without significant
      involvement of prefrontal cortex. This indicated circuitry related to mental
      performance characterised by a fixed strategy of executing serial manipulation of
      numbers within "internal space". The main aim of this communication is to discuss
      the similarity between circuitry underlying higher order motor control and pure
      cognitive performance.

PMID- 8740217
TI  - Limitation of sensitization to injured parts of receptive fields in human skin C
      nociceptors.
AB  - Unmyelinated cutaneous mechano-heat fibers (CMH) in the peroneal nerve of healthy
      human volunteers were studied by means of a "marking" technique which allows
      stable recordings from identified single units over extended periods.
      Mechanoreceptive field sizes were 105 +/- 13 mm2 in 25 units. These large
      receptive fields indicate extensive terminal branching of C fibers in the skin of
      foot and lower leg. Sensitization of CMHs was tested by assessment of thresholds
      for mechanical (von Frey hair) and heat stimuli before and after topical
      application of mustard oil (allyl isothiocyanate) and capsaicin (8-methyl-N
      vanillyl-6-noneamide). While in a group of 14 CMHs the entire receptive field was
      treated with these irritant substances, in another group of 11 CMH units only
      parts of the receptive field were treated to check for signs of spreading
      sensitization through axon collaterals. Mustard oil application did not change
      mechanical thresholds, regardless of whether parts of or complete receptive
      fields were treated. However, mean heat thresholds dropped by 5.6 degrees C to
      36.5 +/- 1.5 degrees C in completely treated receptive fields and by 5.7 degrees
      C to 37.3 +/- 3.4 degrees C in treated parts of receptive fields ("primary
      sensitization"). In contrast, heat thresholds in the nontreated parts did not
      change significantly (42.1 +/- 3.4 degrees C vs 41.2 +/- 3.9 degrees C), i.e.
      "secondary sensitization" to heat was lacking. The absence of primary
      sensitization to probing with von Frey hairs indicates that sensitization of
      insensitive C fibers and recruitment of insensitive axon collaterals may be more
      important for mechanical hyperalgesia than sensitization of conventional CMH
      units-apart from the contribution of central mechanisms. The lack of spread of
      sensitization to untreated parts of the receptive fields o CMHs ("secondary
      sensitization") indicates that this fiber group is probably not involved in any
      form of secondary hyperalgesia to heating.

PMID- 8740218
TI  - The relative contribution of retinal and extraretinal signals in determining the
      accuracy of reaching movements in normal subjects and a deafferented patient.
AB  - This experiment investigated the relative extent to which different signals from
      the visuo-oculomotor system are used to improve accuracy of arm movements.
      Different visuo-oculomotor conditions were used to produce various retinal and
      extraretinal signals leading to a similar target amplitude: (a) fixating a
      central target while pointing to a peripheral visual target, (b) tracking a
      target through smooth pursuit movement and then pointing to the target when its
      excursion ceased, and (c) pointing to a target reached previously by a saccadic
      eye movement. The experiment was performed with a deafferented subject and
      control subjects. For the deafferented patient, the absence of proprioception
      prevented any comparison between internal representations of target and limb
      (through proprioception) positions during the arm movement. The deafferented
      patient's endpoint therefore provided a good estimate of the accuracy of the
      target coordinates used by the arm motor system. The deafferented subject showed
      relatively good accuracy by producing a saccade prior to the pointing, but large
      overshooting in the fixation condition and undershooting in the pursuit
      condition. The results suggest that the deafferented subject does use oculomotor
      signals to program arm movement and that signals associated with fast movements
      of the eyes are better for pointing accuracy than slow ramp movements. The
      inaccuracy of the deafferented subject when no eye movement is allowed (the
      condition in which the controls were the most accurate) suggests that, in this
      condition, a proprioceptive map is involved in which both the target and the arm
      are represented.

PMID- 8740219
TI  - The perception of movements elicited by magnetic cortex stimulation depends on
      the site of stimulation.
AB  - Previous reports suggest that magnetic cortical stimulation (MCS) of the motor
      cortex can elicit a sensation of movement (kinaesthesia) in paralysed limbs. To
      assess this sensory effect of MCS, we examined the accuracy of kinaesthetic
      perception of stimulus-induced right elbow flexion in six blindfolded, healthy
      subjects. Matching of movements elicited by MCS was compared with matching of
      passive elbow movements. Small flexion movements between 1.5 and 5 degrees of
      angle were regularly overestimated by 50-100% when induced by MCS over the
      parietal cortex, whereas movements elicited by MCS over the frontal cortex or by
      passive elbow flexion were accurately estimated. Our results provide data
      compatible with the hypothesis of the existence of a "central sense of movement".
      Activation of collateral branches projecting from the motor cortex to the sensory
      could be the underlying mechanism to this phenomenon.

PMID- 8740220
TI  - Responses to paired transcranial magnetic stimuli in resting, active, and
      recently activated muscles.
AB  - Transcranial magnetic stimulation (TMS) causes the corticospinal system to become
      refractory to subsequent stimuli for up to 200 ms. We examined the phenomenon of
      paired pulse inhibition with TMS under conditions of rest, ongoing voluntary
      activation (isometric force generation), and at variable delays following
      activation (postactivation) of the wrist extensors of seven normal subjects.
      Paired stimuli were delivered to the motor cortex with a circular coil at 1.1
      times motor evoked potential (MEP) threshold, with various interstimulus
      intervals. Voluntary activation caused a marked decrease in the variability of
      the ratio of the amplitude of the MEP evoked by the test pulse to that of the MEP
      evoked by the conditioning pulse. Marked inhibition of the MEP evoked by the test
      pulse was still present. Postactivation, however, caused a dramatic reversal of
      the inhibitory effect of the conditioning pulse in all subjects at interstimulus
      intervals ranging from 40 to 120 ms. This effect lasted for up to 10 s following
      the cessation of activation. MEPs to transcranial electrical stimulation were
      also inhibited by conditioning TMS, but postactivation did not reverse this
      inhibition, indicating that the reversal of paired pulse inhibition is
      intracortical. We conjecture that paired pulse inhibition reflects activity of
      inhibitory interneurons or inhibitory connections between cortical output cells
      that are inactivated in the postactivation state.

PMID- 8740221
TI  - The capacity to accumulate cyclic AMP in the preoptic-anterior hypothalamic area
      of the rat is affected by the exposition to low ambient temperature and the
      subsequent recovery.
AB  - The accumulation of adenosine 3':5'-cyclic monophosphate (cAMP) was measured in
      the preopticanterior hypothalamic area, the cerebral cortex, and the hippocampus
      of rats exposed to different ambient temperatures: (1) 23 +/- 0.5 degrees C, for
      53 h +/- 20 min (control); (2) -10 +/- 1 degrees C, for 53 h +/- 20 min (exposure
      to low ambient temperature); (3) -10 degrees C for 48 h and 23 degrees C for the
      following 5 h +/- 20 min (recovery). The capacity to accumulate cAMP was tested
      by subjecting animals to acute hypoxia, a stimulus which is known to induce a
      large increase in brain cAMP concentration. In the control condition, hypoxic
      stimulation increases cAMP concentration in all the brain regions studied. In
      contrast, during the exposure to low ambient temperature, whilst both the
      cerebral cortex and the hippocampus show the same levels of accumulation found in
      the control condition, cAMP accumulation is reduced in the preoptic-anterior
      hypothalamic area. However, during the first few hours of the recovery period,
      the preoptic-anterior hypothalamic area is able to reattain the capacity for cAMP
      accumulation observed in the control condition.

PMID- 8740222
TI  - Place- and behavior-independent sensory triggered discharges in rat hippocampal
      CA1 complex spike cells.
AB  - To test for access of spatial cues to the hippocampus of unrestrained animals,
      single unit recordings of CA1 complex spike cells were made in thirsty rats as
      they made alternating visits between the center and corners of an enclosed 60 x
      60 cm square arena. At intervals, all lights were turned off in the arena and it
      was rotated. Although no neuronal discharge activity was found that encoded the
      rotation angle, 11 of 97 neurons were selectively activated after lights were
      turned off or on. This activity began at delays of up to several seconds and
      persisted for tens of seconds. These discharges had no location selectivity or
      behavioral correlates and continued even as the rat performed several behaviors
      in different parts of the arena. This confirms similar results in restrained
      rabbits while showing for the first time that this neuronal activity can be
      independent of place and behavior. In addition this shows that sensory stimuli
      can trigger hippocampal discharges even when the rat is not required to make any
      behavioral responses to them.

PMID- 8740223
TI  - Desynchronized (REM) sleep inhibition induced by carbachol microinjections into
      the nucleus basalis of Meynert is mediated by the glutamatergic system.
AB  - The aim of this paper was to study the effects of microinjections of carbachol, a
      mixed cholinergic agonist, into the nucleus basalis of Meynert (NBM) of rats on
      the wake-sleep cycle. Carbachol (2.74 nmol) was able to increase wakefulness (W)
      and decrease desynchronized sleep (DS). To verify the hypothesis that the effects
      of carbachol are at least partially mediated by the glutamatergic system, the
      NMDA antagonist 2-amino-5-phosphonopentanoic acid and the non-NMDA antagonist D
      gamma-glutamylaminomethanesulfonic acid were injected into the NBM before
      carbachol. Pretreatment with these glutamate receptor antagonists counteracted
      the effect of carbachol on DS. The effect of carbachol on W was not modified by
      the pretreatment with the glutamate receptor antagonists. This is the first study
      showing that carbachol injected into the NBM increases W and decreases
      spontaneous DS in the rat. Moreover, our results tend to indicate that the
      decrease in DS following the injection of carbachol into the NBM is related to
      the release of endogenous glutamate.

PMID- 8740224
TI  - Foetal nigral cell suspension grafts influence dopamine release in the non
      grafted side in the 6-hydroxydopamine rat model of Parkinson's disease: in vivo
      voltammetric data.
AB  - The present study employed differential-pulse voltammetry to assess the influence
      of foetal ventral mesencephalic grafts on dopamine overflow in the contralateral
      caudate putamen of the 6-hydroxydopamine rat model of Parkinson's disease. The
      experimental design involved measurements of dopamine overflow in the grafted and
      contralateral striatum. Control measurements of dopamine overflow were performed
      in 6-hydroxydopamine-lesioned rats only and the caudate putamen of normal control
      rats. Cell suspensions of foetal rat ventral mesencephalic tissue were grafted
      into the dopamine-depleted caudate putamen of unilaterally 6-hydroxydopamine
      lesioned rats. At 6 weeks, animals with functional, mature grafts (as assessed by
      amphetamine-amplified behavioural asymmetry), were pretreated with pargyline (75
      mg/kg i.p.), and both striatal sides were monitored for dopamine overflow for 90
      min following amphetamine sulphate administration (5 mg/kg i.p.). The time course
      of dopamine overflow inside the graft was similar to that in the contralateral
      caudate putamen of the same animal, the normal control animal and the
      contralateral caudate putamen of 6-hydroxydopamine-lesioned animals. However, in
      grafted animals the mean dopamine overflow detected in the contralateral caudate
      putamen was approximately 34% lower than the concentration of dopamine detected
      in the contralateral caudate putamen of 6-hydroxydopamine-lesioned control
      animals and approximately 39% lower than the concentration of dopamine detected
      in the caudate putamen of the normal control animal. There was no statistical
      difference in the concentration of amphetamine-induced dopamine overflow between
      the caudate putamen contralateral to the 6-hydroxydopamine lesion and the caudate
      putamen of the normal control animal. These data suggest that intrastriatal
      foetal ventral mesencephalic suspension grafts reduce amphetamine-induced
      dopamine release in the contralateral non-grafted caudate putamen.

PMID- 8740225
TI  - Early-onset dementias: clinical, neuropathological and genetic characteristics.

PMID- 8740226
TI  - Monoamine oxidase B inhibitor selegiline protects young and aged rat peripheral
      sympathetic neurons against 6-hydroxydopamine-induced neurotoxicity.
AB  - Selegiline is a selective and irreversible monoamine B inhibitor with the
      capacity to increase the level of several antioxidative enzymes in rat brain. It
      can protect adrenergic neurons against injury induced by neurotoxins such as
      MPTP, DSP-4 and AF64A in animal studies. In addition, the protective action is
      not limited to catecholaminergic cells, as selegiline can also minimize the loss
      of developing motoneurons after axotomy. The aim of this study was to determine
      whether selegiline can protect peripheral catecholaminergic neurons against the
      neurotoxic effect of 6-OHDA. This kind of protective effect against 6-OHDA
      neurotoxicity has not been reported before. Wistar albino male rats aged 4 or 24
      months were treated with selegiline or saline solution 1 h before 6-OHDA
      injection. At 2 weeks after the 6-OHDA injection, the superior cervical ganglia
      (SCG) and submandibular glands (SMG) were studied using catecholamine
      histofluorescence and immunohistochemistry for tyrosine hydroxylase (TH). The
      number of TH-positive cells in the SCG and the length and number of adrenergic
      nerve fibers in the SMG were quantified. Our findings showed that 6-OHDA caused a
      reduction of TH immunoreactivity and catecholamine histofluorescence in neuronal
      somata, as well as a decrease in the number and length of adrenergic nerve fibers
      in the submandibular gland. Selegiline pretreatment protected SCG neurons and
      their postganglionic nerve fibers in SMG against these changes in a dose
      dependent manner. The mechanism through which selegiline exerts its
      neuroprotective effect is as yet unknown.

PMID- 8740227
TI  - Convergence of Lewy bodies and neurofibrillary tangles in amygdala neurons of
      Alzheimer's disease and Lewy body disorders.
AB  - Amygdalae of patients with Alzheimer's disease (AD), Parkinson's disease, Down's
      syndrome, diffuse Lewy body disease or a combination of these diseases were
      probed with antibodies to neurofilament proteins as well as with Lewy body (LB)-
      and paired helical filament-specific antibodies. The results indicate that the
      amygdala is severely affected by the accumulation of both neurofibrillary tangles
      (NFTs) and LBs in most cases of the diseases mentioned above, and that amygdala
      LBs have a similar epitope composition to that of LBs in the brain stem and
      cerebral cortex. While large numbers of both LBs and NFTs were seen in different
      neurons within the amygdala, these two lesions frequently occurred together in
      the same neurons of the amygdala. These findings are in contrast to other sites
      that accumulate LBs and NFTs, but rarely both lesions in the same neuron. Thus,
      amygdala neurons may be selectively vulnerable to developing both LBs and NFTs,
      and these inclusions may play a role in the massive degeneration of these neurons
      in AD and LB disorders of the elderly.

PMID- 8740228
TI  - Localization of Menkes gene expression in the mouse brain; its association with
      neurological manifestations in Menkes model mice.
AB  - Menkes gene (Mc1 or MNK, encoding putative copper-transporting ATPase) expression
      was investigated and compared in normal and macular mutant mouse brain. Northern
      blot analysis showed a distinct 8.3-kb transcript and no obvious difference in
      size or extent in normal mice and macular mutants on postnatal days 0, 4, 7, 10
      or 13. In situ hybridization revealed that certain specific populations of cells
      in the brain express Menkes mRNA, and that their localization in normal and
      mutant mice did not differ and was conserved on days 4, 10 and 13. The most
      intense hybridization signals were observed in the hippocampal CA1 region and
      dentate gyrus, the olfactory bulb nuclei, the cerebellar granular cell layer, the
      choroid plexus and the ependyma, with less intense signals in the hippocampal CA3
      region and cerebellar Purkinje cells. In addition, necrotic neuronal cell death
      was predominantly observed in the CA3 region and the Purkinje cells of macular
      mice after postnatal day 10. The finding that the regions that had lower
      expression level of Menkes mRNA corresponded to those showing neuronal necrosis
      suggests that the Menkes gene may be responsible for the neuronal degeneration in
      some specific portions of the brain and clinical manifestations in this mutant.

PMID- 8740229
TI  - Mechanism of increasing dystrophin-positive myofibers by myoblast
      transplantation: study using mdx/beta-galactosidase transgenic mice.
AB  - Female mdx/mdx mice were crossed with non-dystrophic transgenic males expressing
      the beta-galactosidase (beta-gal) gene under a muscle-specific promoter
      (TnILacZ1/29). All male offspring were mdx mice and about 50% of them also
      expressed the beta-gal gene. The beta-gal/mdx mice were selected as recipients
      for the transplantation of myoblasts from non-transgenic normal BALB/c mice. When
      host muscles were not irradiated before myoblast transplantation, 4.6% of the
      muscle fibers in host muscles were dystrophin positive 1 month after
      transplantation. Most of these dystrophin-positive muscle fibers were also beta
      gal positive. About one quarter of these fibers are the result of reverse
      mutations; most of them have, however, been produced by fusion of donor myoblasts
      with host muscle fibers or with host myoblasts. The virtual absence of beta-gal
      negative fibers indicates that there were no exclusively donor-donor fusions.
      When host muscles were irradiated before myoblast transplantation, roughly the
      same percentage (5.5%) of dystrophin-positive fibers were formed in the injected
      muscle, but 42% of them were beta-gal negative. These beta-gal-negative
      dystrophin-positive muscle fibers were formed by the exclusive fusion of donor
      myoblasts with one another rather than with host cells. This clearly indicates
      that myoblast transplantation can form completely new muscle fibers or muscle
      fiber segments when host satellite cell proliferation is reduced by irradiation.
      These newly formed muscle fibers had, however, a small diameter and additional
      myoblast transplantation may be required to increase their size. This situation
      has some similarities with findings in Duchenne muscular dystrophy patients of
      more than 6 years of age, who also have a limited proliferation capacity of their
      satellite cells.

PMID- 8740230
TI  - Investigation on the expression of major histocompatibility complex class II and
      cytokines and detection of HIV-1 DNA within brains of asymptomatic and
      symptomatic HIV-1-positive patients.
AB  - Among the various mechanisms proposed to explain the pathogenesis of cerebral
      lesions in human immunodeficiency virus (HIV)-induced encephalitis, a cytokine
      mediated action has found most favour. Indeed, elevated expression of cytokines
      such as interleukin (IL)-1 and tumor necrosis factor-alpha (TNF-alpha), thought
      to be neurotoxic, has been found in AIDS patients. As a previous study had
      demonstrated the presence of HIV proviral DNA in brain tissue of a number of HIV
      positive non-AIDS patients, we undertook this present investigation using
      morphological, immunohistochemistry (IHC) and polymerase chain reaction (PCR)
      methods to detect the expression of major histocompatibility complex (MHC) class
      II molecules, the presence of HIV-1 proviral DNA and of the cytokines TNF-alpha,
      IL-1 alpha, IL-4 and IL-6 in brains of the same group of individuals. The study
      included brains of 36 asymptomatic HIV-1 positive patients and the results were
      compared with those of AIDS patients either affected by HIV encephalitis (n = 8)
      or exempt from any neuropathological changes (n = 10) as well as of normal
      controls (n = 5). Results show that: HIV proviral DNA could be detected by PCR in
      17 out of the 36 brains from HIV-positive pre-AIDS cases; most (15 of 17) of PCR
      positive brains showed minimal to severe expression of MHC class II antigen; and
      cytokines could be detected predominantly within white matter even at this early
      stage. The data demonstrated that the state of immune activation described in
      AIDS is already present at the pre-AIDS stage and suggest that the presence of
      cytokines may already trigger the cascade of events leading to brain damage.

PMID- 8740231
TI  - Clinical and histopathological analysis of proliferative potentials of recurrent
      and non-recurrent meningiomas.
AB  - Proliferative potentials of meningiomas from 127 patients were examined
      immunohistochemically using the anti-Ki-67 monoclonal antibody, MIB-1, on
      paraffin sections, and the correlation among MIB-1 staining index (SI),
      histopathological finding, and clinical course of the disease was analyzed
      retrospectively. The mean MIB-1 SI of 50 male patients with meningioma was 5.5%,
      whereas that of 77 female patients was 2.7%. Higher MIB-1 SI were observed for
      younger patients. These age- and sex-related differences in MIB-1 SI were
      statistically significant. The patients were assigned to one of three groups:
      those with non-recurrent meningioma (n = 73); those with recurrent meningioma in
      whom the specimens obtained during the initial surgery were used to calculate the
      MIB-1 SI (n = 21); and those with recurrent meningioma for whom the specimens
      obtained during the surgery for recurrent tumors were used to calculate the MIB-1
      SI (n = 33). The mean MIB-1 SI in these patients were 1.6%, 3.6%, and 8.8%,
      respectively, and there were statistically significant differences among these
      three groups. Statistical analyses reveal that meningiomas with a MIB-1 SI of 3%
      or more have a significantly high tendency for recurrence during the clinical
      courses, especially within the first 10-year follow-up periods. Moreover, there
      is statistically significant correlation between MIB-1 SI and recurrence in each
      Simpson's grade. The time interval to the next recurrence for recurrent
      meningiomas is associated with the proliferative potential represented by the MIB
      1 SI, and a correlation equation has been proposed to predict the date of the
      next recurrence. Analyses on cellularity of meningiomas revealed no statistically
      significant difference in cellularity between non-recurrent and recurrent
      meningiomas. There was no statistically significant relationship between
      cellularity and MIB-1 SI of meningiomas. In conclusion, examination on
      proliferative potentials of meningiomas using MIB-1 SI is very important for
      biological and histopathological analyses and the prediction of future
      recurrence.

PMID- 8740232
TI  - Hydrolethalus: a midline malformation syndrome with optic nerve coloboma and
      hypoplasia.
AB  - Ophthalmic pathological findings of hydrolethalus, a midline malformation
      syndrome, were determined in three fetuses aborted between the 14th and 19th
      gestational week. The eyes were serially sectioned and analyzed using light
      microscopy and a panel of 13 antibodies to neuronal, glial, epithelial, and
      mesenchymal elements of the eye. The general morphological and antigenic
      development of the anterior segment, retina and choroid were normal, but some
      lens fibers were vacuolated and irregular in all eyes. A coloboma of the optic
      nerve was constant and corresponded in its severity to the systemic
      manifestations. It ranged from segmental dysplasia of the optic nerve head to a
      colobomatous orbital cyst with secondary microphthalmos and deranged development
      of the eye. Glial tissue extended through a defect in the sheaths of the optic
      nerve in three eyes, communicating with retinoblastic tissue in the orbit.
      Evidence of secondary optic nerve hypoplasia was present in all eyes, and a
      separate chorioretinal coloboma was present in one eye. Ocular anomalies should
      be considered one hallmark of hydrolethalus syndrome, and they may help to
      differentiate it from other overlapping malformation syndromes. In particular,
      colobomatous dysplasia and hypoplasia of the optic nerve seem to be typical of
      hydrolethalus syndrome. Histopathological studies of the eyes may help the
      neuropathologist in making the differential diagnosis of midline malformation
      syndromes.

PMID- 8740233
TI  - Inflammatory infiltrates and complete absence of Purkinje cells in anti-Yo
      associated paraneoplastic cerebellar degeneration.
AB  - We studied the nervous systems and tumors of two patients with anti-Yo-associated
      paraneoplastic cerebellar degeneration (PCD). In both patients the underlying
      tumor was an ovarian adenocarcinoma that expressed Yo antigens and contained
      extensive infiltrates of lymphocytes and plasma cells. The major central nervous
      system findings were a complete loss of cerebellar Purkinje cells with Bergmann
      astrogliosis. One patient had inflammatory infiltrates in the medulla and pons,
      and moderate axonal loss and demyelination involving the spinal cord. No
      inflammatory infiltrates were identified in the cerebrum, cerebellum or brain
      stem of the other patient. Using quantitative Western blot analysis, deposits of
      anti-Yo IgG could not be demonstrated in the nervous system, possibly as a result
      of the loss of cells expressing Yo antigens. The detection of the anti-Yo
      antibody as a common marker of PCD in one patient with inflammatory infiltrates
      and another without infiltrates suggests that some PCD pathologically classified
      as "non-inflammatory" may represent a final burn-out stage of a cellular immune
      mediated disorder. Our findings indicate that Purkinje cells are the main, but
      not necessarily the exclusive, targets of this disorder.

PMID- 8740234
TI  - A quantitative comparison of plaque types in Alzheimer's disease and senile
      dementia of the Lewy body type.
AB  - In a previous study we reported no difference in the overall beta-amyloid protein
      (beta AP) load between Alzheimer's disease (AD) and senile dementia of the Lewy
      body type (SDLT). However, it is possible that differences in the morphology of
      beta AP plaque types exist, analogous to the differences in cytoskeletal
      pathology found in these two disorders. We have carried out a quantitative image
      analysis of plaque subtypes in the temporal lobe of AD (n = 8), SDLT (n = 9) and
      control (n = 11) cases. Measurements of beta AP load and plaque density were
      consistently higher in AD and SDLT than in controls. When AD and SDLT cases were
      compared no differences were seen in either the density or relative proportions
      of classic and diffuse plaques. Based on these results we suggest that the
      variation in the clinical course of these diseases reflects differences in the
      cytoskeletal pathology, whereas the final stages of profound dementia common to
      both disorders is associated with the deposition of beta AP.

PMID- 8740235
TI  - Cytochrome c oxidase deficiencies in the muscle of patients with inflammatory
      myopathies.
AB  - We studied mitochondrial function in inflammatory myopathies, using cytochrome c
      oxidase (COX) reaction on muscle biopsy samples from 30 patients (15 with
      dermatomyositis, 12 with polymyositis, and 3 with inclusion body myositis) and 30
      age-matched controls. We also performed immunocytochemistry for COX II and COX IV
      subunits in 7 of these patients who had COX deficiency. COX-deficient fibers were
      a constant finding in patients or controls older than 65 years and the percentage
      of COX-deficient fibers correlated with age in both patients and controls. Focal
      COX deficiency was found in 24 patients (13 of 15 with dermatomyositis, 8 of 12
      with polymyositis, and 3 of 3 with inclusion body myositis) and 18 controls. The
      percentages of COX-deficient fibers were higher in patients with inflammatory
      myopathies (range: 0-4.7%; mean: 1.2%) than in age-matched controls (range: 0
      1.9%; mean: 0.4%) (P < 0.01). In the subgroup of patients under age 65, COX
      deficient fibers were more frequent in dermatomyositis than in polymyositis
      (mean: 0.8% vs 0.2%, P = 0.02). In patients with dermatomyositis, capillary loss
      correlated positively with COX deficiency (P < 0.02). Immunocytochemistry for COX
      II and IV showed that 82% of COX-negative fibers were COX II-negative and 26%
      were COX IV-negative, suggesting that proteins encoded by mitochondrial DNA are
      predominantly, but not exclusively, involved in COX deficiency. We conclude that
      mitochondrial dysfunction and COX deficiency can occur in inflammatory
      myopathies. Such a mitochondrial dysfunction is not solely related to the aging
      process. We suggest that muscle ischemia contributes to mitochondrial dysfunction
      in dermatomyositis.

PMID- 8740236
TI  - Experimental hydranencephaly in the ovine fetus.
AB  - Hydranencephaly is defined as the replacement of a previously normal brain, in
      whole or in part, by membranous fluid-filled sacs. The etiology is not well
      understood, and the time course of development is unknown. Fifteen ovine fetuses
      were chronically cannulated and had both carotid arteries ligated at 100 days of
      gestation (term is 145-150 days). They were killed at 1 (n = 4), 2 (n = 6) and 4
      (n = 5) weeks post-surgery, and the findings compared with those of 25 age
      matched controls. By 2 weeks post-surgery the entire cerebral hemispheres and
      diencephalon had been replaced by fluid closely resembling cerebrospinal fluid.
      The choroid plexus, pituitary and brain stem remained outwardly normal, but the
      cerebellum showed signs of damage. Fetuses maintained normal values for blood
      gases and hematocrit up to 4 weeks post-surgery, and grew normally. Light
      microscopy of the brain stem showed significant losses of cell populations in the
      medulla by 4 weeks. Vascular casting and acute blood flow studies in an
      additional group of fetuses showed that the entire brain was perfused via the
      vertebral-occipital anastomosis immediately after acute bilateral carotid
      clamping, but that the blood flow rate was insufficient to maintain adequate
      oxygen delivery.

PMID- 8740237
TI  - A study of pathology of a bovine primary peripheral myelinopathy with features of
      tomaculous neuropathy.
AB  - Cases of a bovine neuropathy are reported in which peripheral nerves show
      "sausage-shaped" thickenings of the myelin sheaths at different sites of the
      internode. Clinical signs of dysphagia and chronic rumenal bloat developed after
      weaning which were attributable to bilateral vagus nerve degeneration. Trunks of
      the sciatic nerves and brachial plexuses were similarly affected with the animal
      adopting a weak shuffling gait. Affected animals were the progeny of sire
      daughter matings. The lesions are similar to those seen in the tomaculous
      neuropathies of man. The present study is believed to be the first report of this
      lesion occurring in domestic animals.

PMID- 8740238
TI  - Melanotic astrocytoma.
AB  - A case of pigmented pilocytic astrocytoma (WHO grade I) incidentally found in a
      right temporopolar lobectomy specimen is reported. The patient, a 41-year-old
      woman, underwent surgery because of long-standing complex partial epilepsy of
      presumed post-traumatic origin. Using immunohistochemistry and electron
      microscopy, the tumor was shown to be composed of astrocytes without evidence of
      neurosecretory or melanocytic differentiation. The cytoplasmic pigment was
      identified as neuromelanin by its histochemical staining properties and
      ultrastructure. Although rare cases of ependymoma, subependymoma, choroid plexus
      papilloma and ganglioglioma with melanogenesis are on record, no melanotic
      astrocytoma has been described so far.

PMID- 8740239
TI  - Rosai-Dorfman disease presenting with multiple orbital and intracranial masses.
AB  - Rosai-Dorfman disease is an idiopathic histocytic proliferative disorder
      typically characterized by painless cervical adenopathy, fever, and weight loss.
      Extranodal manifestations are responsible for presentation in approximately 25%
      of patients. Orbital involvement has been described in about 10% of patients.
      There have been only 16 reported cases of Rosai-Dorfman disease presenting with
      an intracranial mass. We report an unusual case of a patient presenting with
      bilateral orbital tumors as well as multiple intracranial masses. Clinical,
      magnetic resonance imaging, and histopathological features are discussed.

PMID- 8740240
TI  - Anomalous effects of hormone fragments on the measurement of parathyroid hormone
      by radioimmunoassay.
AB  - One of the basic assumptions underlying the use of radioimmunoassay and other
      competitive protein-binding assays is the homogeneity of the antigen or ligand.
      This assumption is not valid for the measurement of parathormone (PTH) because of
      the presence of fragments. Hence, there is a potential for errors and high
      variability in the measurement of parathyroid hormone (PTH) by radioimmunoassay.
      Even though region-specific radioimmunological and immunoradiometric assays for
      PTH measurement can overcome some of the difficulties caused by the presence of
      hormone fragments, the possibility for serious measurement errors still remains.
      We therefore examined experimentally and by modeling the impact of fragments on
      the estimation of the concentration of a highly purified intact bovine
      parathyroid hormone by radioimmunoassay. Our experimental results show that the
      mere presence of fragments can lead to a significant underestimation or
      overestimation of the amount of the intact hormone. The results have been
      simulated by a model in which fragments bind to the antibodies, thus competing
      with the intact hormone, and to the intact hormone as well, thereby reducing the
      amount of free intact hormone in competition with the radioligand. This work
      indicates that it may be preferable to consider alternative methods, other than
      competitive protein-binding assays, for the measurement of secreted PTH.

PMID- 8740241
TI  - Nitric oxide (EDRF) enhances the vasorelaxing effect of dihydropyridine calcium
      antagonists in isolated human middle cerebral arteries.
AB  - Experiments were performed on perfused human middle cerebral artery (MCA)
      precontracted with prostaglandin F2a. Nifedipine, isradipine and lacidipine
      induced dose-dependent relaxant effects on MCA segments. Effects of nifedipine
      were rather similar on MCA segments with and without endothelium; however,
      responses of endothelium-denuded vessel segments to isradipine and especially
      lacidipine were lower than those of vessels with intact endothelium. The
      vasodilator effects of these agents, especially isradipine and lacidipine, on
      vessel segments with intact endothelium in the presence of a NO-synthase
      inhibitor, N-nitro-L-arginine, were significantly attenuated whereas a
      cyclooxygenase inhibitor, indomethacin, did not significantly alter vasodilator
      responses of MCA segments to all calcium antagonists tested. It is suggested that
      the endothelium modulates vascular relaxation to dihydropyridines by an
      enhancement of calcium antagonist actions by basally released EDRF/NO at the
      level of vascular smooth muscles or by a dihydropyridine-induced increase in the
      release of EDRF/NO.

PMID- 8740242
TI  - The effects of repetitive mild brain injury on cytoskeletal protein and behavior.
AB  - The purpose of this study was to examine the hypothesis if repetition of mild
      mechanical brain injury induces the pathological process related to Alzheimer's
      disease. After defining the magnitude of the subthreshold brain injury which does
      not induce brain tissue damage by a single hit, the subthreshold mild impact (1.0
      atm) was repeated 7 times every 24 h. One week after the last impact, abnormal
      accumulation of microtubule-associated protein 2 (MAP2) and phosphorylated
      neurofilament 200 kD (p-NFH) was observed in neuronal perikarya and dendrites.
      One month after percussion, the number of MAP2-and p-NFH-positive neuronal
      perikarya was increased and observed in remote areas including the contralateral
      cortex and the hippocampus. Tau-1 immunoreactivity was increased in deep cortical
      neurons of the ipsilateral side after dephosphorylation, indicating the
      accumulation of phosphorylated tau in neuronal perikarya. The abnormal
      accumulation of cytoskeletal proteins in neuronal perikarya may be due to
      impaired axonal transport caused by mechanical brain injury. The behavioral study
      revealed that after repetitive mild percussion, rats show less efficient
      habituation to a new environment. It is suggested that the repetition of
      subthreshold mechanical brain injury may trigger cytoskeletal alteration related
      to neuronal degeneration.

PMID- 8740243
TI  - Selective uptake of the anticancer drug bendamustine by liver and kidney tissues
      following its intravenous administration to mice.
AB  - Distribution of 14C-bendamustine following intravenous (i.v.) administration to
      mice was examined by whole body autoradiographic (WBAR) and quantitative
      techniques. The WBAR study showed that 14C-bendamustine-derived radioactivity was
      distributed extremely unevenly at each time interval investigated. After 5 min of
      administration the highest density of radioactive material was found in the liver
      and in the kidney. At all time intervals investigated the brain remained free of
      the label. In a detailed quantitative distribution study it was found that 14C
      bendamustine-derived radioactivity was also unevenly distributed throughout the
      mouse tissues. At 5 min postdosing the level of 14C was by one order higher in
      the liver and in the kidney in comparison to the lungs, heart, spleen, and
      muscle. The results of both WBAR and quantitative tissue distribution studies
      suggest that bendamustine was selectively taken up from the blood by liver and
      kidney tissues. Because of this pharmacokinetic property, dose modification
      should be taken into consideration when administering the drug to patients
      suffering from hepatobiliary and kidney disorders.

PMID- 8740244
TI  - Influence of cholesterol-lowering on plasma membrane lipids and function.
AB  - In order to determine whether alterations in membrane or plasma lipids affect
      transmembrane cationic transport systems in erythrocytes and platelets, cationic
      fluxes and intracellular concentrations, membrane lipids, plasma lipids,
      lipoproteins and apolipoproteins were measured in hypercholesterolemic patients
      before and during administration of a HMG-CoA reductase inhibitor. After a 1
      month placebo run-in period, the patients were treated double-blind either with
      placebo (n = 25) or with pravastatin (n = 25) for 6 months. Placebo or
      pravastatin 10 mg during the 1st month, 20 mg during the 2nd month and 40 mg
      during the additional 4 months was administered once daily in the evening. Blood
      was collected in the morning after an overnight fast for assay of membrane and
      plasma lipids and of cationic fluxes and concentrations, at the end of the
      placebo run-in period and after 1, 2, 3 and 6 months of pravastatin therapy.
      Compared to the placebo group the plasma concentration of total cholesterol and
      phospholipids, free cholesterol and cholesterol esters, and plasma LDL
      cholesterol and LDL-phospholipids were decreased during 6 months of pravastatin
      therapy. No changes in plasma VLDL-, HDL-, HDL2- or HDL3-cholesterol,
      phospholipids or triglycerides were observed in the pravastatin-treated patients.
      A decrease in the plasma level of apolipoprotein B and of LDL-apo B, but not of
      VLDL-apo B, was observed during pravastatin therapy; the plasma apolipoprotein AI
      and AII levels, as well as HDL2- and HDL3-apo AI and apo AII levels, however,
      remained unchanged. Plasma lipoprotein Lp(a) did not change during pravastatin
      therapy, while the plasma lecithin cholesterol acyltransferase activity (LCAT)
      increased. Compared to the placebo group the erythrocyte and platelet membrane
      cholesterol content was reduced in the pravastatin-treated patients. The
      intraerythrocyte and intraplatelet Na+ concentration was reduced during
      pravastatin administration, while the erythrocyte and platelet Na+/K+ pump
      activity was increased. However, the intraerythrocyte and intraplatelet K+, Mg2+,
      cytosolic Ca2+ concentration and water content as well as the erythrocyte Na+/Li+
      countertransport and Na+/K+ cotransport activity and the Na+ and K+ leak were not
      changed during pravastatin treatment. Our data show that cholesterol lowering in
      hypercholesterolemic patients may result in a significant decrease in erythrocyte
      and platelet membrane cholesterol content. These changes in plasma membrane
      cholesterol are accompanied by an increase in the Na+ pump activity and a
      decrease in intracellular Na+ concentration. Whether these changes in membrane
      lipids and function observed during cholesterol lowering also occur in other
      cells remains to be further elucidated.

PMID- 8740245
TI  - Effect of growth hormone releasing hormone on growth hormone, prostaglandin E2
      and insulin in non-insulin-dependent diabetic patients.
AB  - In a previous paper we demonstrated a link between growth hormone releasing
      hormone (GHRH) and prostaglandin E2 (PGE2) in their action on growth hormone (GH)
      in normal subjects. However, in diabetes mellitus various disturbances of GH and
      PGE2 secretion have been reported. In the present study the response of GH, PGE2
      and insulin to GHRH (1 microgram/kg b.w.) intravenously was investigated in 12
      poorly controlled non-insulin-dependent diabetic patients (8 males and 4 females)
      and 10 normal volunteers (5 males and 5 females). After GHRH injection, GH
      increased in diabetic patients from 2.28 +/- 0.52 mU/l to 14.76 +/- 1.29 mU/l at
      30 min (p < 0.001). This response was not statistically different compared to the
      control subjects. The basal values of plasma PGE2 were significantly lower in
      diabetic patients than in control subjects. GHRH induced a slight but significant
      increase of PGE2 in normal subjects (9.80 +/- 0.44 pg/ml at 0 min; 14.50 +/- 1.30
      pg/ml at 90 min, p < 0.05) and did not have any effect on PGE2 in diabetic
      patients. Serum insulin decreased significantly after GHRH in both normal
      subjects and diabetic patients at 60 min. We conclude that GH response to GHRH is
      not significantly impaired in poorly controlled non-insulin-dependent diabetic
      patients. The lack of an effect of GHRH on PGE2 in diabetic subjects provides
      further evidence of abnormal PGE2 synthesis or metabolism in this disorder. The
      physiological significance of the GHRH suppressive effect on serum insulin
      remains to be explained.

PMID- 8740246
TI  - Yawning behavior for preclinical drug evaluation.

PMID- 8740247
TI  - Aqueous flare in eyes with senile disciform macular degeneration: correlation
      with clinical stage and area of neovascular membrane.
AB  - BACKGROUND: The aim of the present study was to investigate the aqueous flare in
      eyes with senile disciform macular degeneration (SDMD), divided into different
      clinical stages, and the correlation between the aqueous flare and the area of
      the neovascular membrane. METHODS: Eighty-six eyes of 44 patients with SDMD were
      examined using a laser flare meter. The area of the neovascular membrane was
      measured by means of a digitizer in images obtained using indocyanine green
      videoangiography. RESULTS: The mean value of the aqueous flare was 5.91 +/- 2.51
      (photon count/ms) in 7 predisposing stage eyes, 5.68 +/- 1.64 in 15 initial stage
      eyes, 9.09 +/- 7.65 in 24 advanced form eyes, 5.40 +/- 1.42 in 11 disciform scar
      eyes, and 5.36 +/- 1.72 in 29 fellow eyes. The aqueous flare value was
      significantly (P < 0.01) higher in eyes with the advanced form of SDMD than in
      the fellow eyes. There were no significant differences in aqueous flare values
      between eyes with predisposing stage, initial stage, and disciform scar and
      fellow eyes. The aqueous flare value increased significantly with increasing area
      of neovascular membrane (R = 0.68, P < 0.01). CONCLUSION: The present results
      suggest that the aqueous flare increases with increasing neovascular membrane
      area in eyes with SDMD, and decreases with scarization of the neovascular
      membrane.

PMID- 8740248
TI  - Therapeutic pars plana vitrectomy for chronic uveitis: a retrospective study of
      the long-term results.
AB  - BACKGROUND: Pars plana vitrectomy has both diagnostic and therapeutic potential
      in chronic uveitis. In this paper the therapeutic value of vitrectomy is
      investigated. METHODS: This is a retrospective study on 25 eyes that underwent
      pars plana vitrectomy with therapeutic intent. Surgery was considered in patients
      with severe vitreous clouding or macular pucker and in those who responded poorly
      or not at all to conventional treatment for uveitis. The mean period of follow up
      was 4.5 years, varying from 2 to 12 years. RESULTS: Improved vision was observed
      in 56% of the eyes (14/25). Twenty-four percent of the eyes (6/25) had stable
      vision. Macular edema disappeared in 40% (10/25) of cases and persisted in 60%
      (15/25). Two of the nine eyes with persistent macular oedema progressed to a
      macular hole. Four of the six eyes with macular pucker suffered recurrence, one
      ended in phythisis, while the pucker was cured in only one patient. Twelve
      percent of the eyes (3/25) subsequently experienced a recrudescence of uveitis,
      making systemic treatment necessary. One patient presented, after vitrectomy, a
      traction retinal detachment with proliferating vitreoretinopathy. No
      complications or recurrences were seen in 44% of the eyes (11/25). CONCLUSION:
      Vitrectomy has a definite place in the treatment of chronic uveitis, both on the
      functional level, with improvement or stabilisation of visual acuity and on the
      therapeutic level, with possible reduction or cessation of systemic treatment.

PMID- 8740249
TI  - Indocyanine green and fluorescein angiography of surgically excised macular
      choroidal neovascularizations: correlations with histopathologic and
      ultrastructural findings.
AB  - BACKGROUND: Informations are expected from the histopathological study of
      surgically excised choroidal neovascular membranes (CNMs), particularly in
      relation to the angiographic aspects of vascular architecture. METHODS:
      Fluorescein and indocyanine green (ICG) angiograms were studied together with the
      histopathological features of 12 surgically excised subfoveal CNMs in eyes
      affected by age-related macular degeneration (ARMD). RESULTS: Instead of the
      early and delayed diffuse hyperfluorescence secondary to CNMs observed on
      fluorescein angiography (seven were well defined, five scar evolved), ICG
      revealed (a) very early hypofluorescence of the membrane bulk over the
      fluorescence of the outer choroidal vascular bed and (b) late hyperfluorescence
      gradually increasing and partially defining the border of membranes. CNMs with
      well-defined hyperfluorescent aspects were characterized by fibrovascular bulk
      lined on one side by retinal pigment epithelium. Fibrosis reaction predominated
      over the vascular components in scar-evolved membranes. CONCLUSIONS: Fluorescein
      and ICG angiographic differences in the appearance of CNMs could depend on (a)
      the morphological structure and size of the CNM (b) its location within the
      chorioretinal layers and (c) different molecular characteristics of the dyes
      used.

PMID- 8740250
TI  - Risk factors associated with contrast sensitivity loss in diabetic patients.
AB  - BACKGROUND: Psychophysical tests in patients with diabetes mellitus reveal
      deficits of central vision before the development of overt retinopathy. We
      evaluated the contrast sensitivity thresholds in 30 patients with type II
      diabetes mellitus and without retinopathy, taking into account the crystalline
      lens density. Risk factors for contrast sensitivity deficits were investigated.
      METHODS: Contrast sensitivity was compared in 30 aretinopathic diabetic patients
      and age-matched controls. Contrast thresholds were determined for stationary
      gratings at three spatial frequencies (6, 15, and 27 cycles/deg) and for mesopic
      (5 cd/m2) and low photopic (85 cd/m2) vision. Lens density was measured using a
      IntraOptics opacity lensmeter. RESULTS: Significant contrast sensitivity losses
      at all three spatial frequencies were observed in low photopic and mesopic vision
      in diabetic patients. The optical density of the lens in the diabetic group did
      not differ from that in the controls. Contrast sensitivity deficits were
      positively correlated with patient's age, systolic blood pressure and nephropathy
      at all three spatial frequencies. No relationship between cardiovascular
      autonomic neuropathy and contrast sensitivity defects was observed. CONCLUSIONS:
      These data suggest that contrast sensitivity deficits in diabetic patients
      without retinopathy are not solely explained by a diabetes-induced increases in
      lens optical density. Abnormalities of the retina or its neural connections
      occurring before the onset of clinically detectable retinopathy may be involved.
      Risk factors for these deficits are advanced age, high systolic blood pressure,
      and nephropathy.

PMID- 8740251
TI  - Prospective study design for the Heidelberg Retina Tomograph: the effect of
      change in focus setting.
AB  - BACKGROUND: Image scaling on the Heidelberg Retina Tomograph (HRT) is based on an
      axial model of ametropia. In the longitudinal follow-up of patients, refractive
      changes in ametropia may occur; the HRT interprets such change as being axial in
      origin. This results in an apparent alteration in the size of fundus features
      with time and in reduced sensitivity of the instrument to subtle changes relating
      to disease progression. The aim of this study was to determine the effect of
      changing HRT focus settings on the absolute scaling of topography images.
      METHODS: Seven image series were acquired of the optic nerve head of a single
      emmetropic eye at each of a range of panel focus settings under three conditions:
      (A) emmetropia, (B) trial lens-induced ametropia, (C) contact lens-induced
      ametropia. A masked observer measured the separation between two defined retinal
      vascular bifurcations for each topography image. RESULTS: The measured distance
      decreased with a positive shift in focus. There was a significant difference in
      distance with change in focus setting for all conditions (A P < 0.008, B and C P
      < 0.0001). Over equivalent focus ranges, data from the three groups were not
      significantly different, lying within the 95% confidence limits at each setting.
      The mean standard deviation for the distance measure was 10 microns. CONCLUSION:
      Adjustment in focus settings to compensate for refractive change in eyes of
      stable axial length and keratometry induces a change in the topography measures
      using the HRT. It is recommended that, for the detection of subtle change over
      time, refractive changes are corrected without a change in the panel focus
      setting.

PMID- 8740252
TI  - The effect of concurrent Pseudomonas or Xanthomonas exposure on adherence of
      Acanthamoeba castellanii to soft contact lenses.
AB  - BACKGROUND: Approximately 85% of Acanthamoeba-contaminated contact lens systems
      in asymptomatic patients have concurrent bacterial contamination. Pseudomonas
      aeruginosa and Xanthomonas maltophilia are common contact lens contaminants; we
      investigated the effect of coincubation of Acanthamoeba adherence to contact
      lenses. METHODS: A. castellanii, 1 x 10(5) organisms/ml, was coincubated with P.
      aeruginosa or X. maltophilia, 1 x 10(8) CFU/ml in phosphate-buffered saline.
      Sterile, unworn polymacon, etafilcon A or lidofilcon contact lens were
      investigated. The experimental groups were: (I) lenses exposed to bacteria for 1
      h, then Acanthamoeba for 2 h; (II) lenses exposed concurrently to bacteria and
      Acanthamoeba for 2 h; (III) Acanthamoeba coincubated with bacteria for 24 h, then
      lenses exposed for 2 h; (IV) lenses exposed to Acanthamoeba for 2 h (control).
      RESULTS: For all experimental groups, Acanthamoeba adherence was greater to
      lidofilcon than to polymacon and etafilcon. For both P. aeruginosa and X.
      maltophilia, neither group I nor group II displayed greater Acanthamoeba
      adherence than group IV. Group III exhibited significantly less adherence than
      group IV for lidofilcon and polymacon. The decrease in group III adherence
      reflected an overall decrease in Acanthamoeba trophozoite concentration.
      CONCLUSION: Short bacteria/Acanthamoeba coincubation times did not result in
      increased Acanthamoeba adherence. Twenty-four-hour coincubation resulted in
      decreased adherence for Pseudomonas and unchanged adherence rates for
      Xanthomonas. This model suggests that Pseudomonas or Xanthomonas co-contamination
      does not necessarily facilitate quantitative Acanthamoeba contact lens adherence.

PMID- 8740253
TI  - Quantitative relations in the retinal ganglion cell layer of the rat: neurons,
      glia and capillaries before and after optic nerve section.
AB  - BACKGROUND: To study normal quantitative cellular relations and the effect of
      optic nerve section on neurons, glia and capillaries, morphometry was carried out
      on 24 whole-mount retinae of 12 rats. METHODS: In the left eye the optic nerve
      had been sectioned 30 days before death; the right eyes served as controls. Using
      a cresyl violet stain, cells in the retinal ganglion cell layer were evaluated at
      three distances from the papilla (1.2, 2.4 and 3.6 mm). RESULTS: Gradients for
      density of neurons, glial cells and capillary grid were all within a small range
      (center: mid:periphery = 1.41-1.59: 1.29-1.33: 1.00). For all these distances we
      found a fairly constant ratio among the three histological parameters: 44.7-46.6
      neurons and 2.3-2.6 glial cells were counted per capillary grid square (geometric
      model for the capillary meshwork). Thirty days after section of the optic nerve
      the capillary meshwork remained unaffected (96.2 grid squares/mm2 before nerve
      section vs 94.7 grid squares/mm2 after nerve section) while glial cells had more
      than doubled (238 vs 498 cells/mm2) and nearly half of all neurons had gone (4371
      vs 2244 cells/mm2). Size characteristics of amacrine cells were similar for all
      three eccentricities, whereas peripheral retinal ganglion cells tended to be
      considerably larger than central ones. CONCLUSIONS: Cresyl violet stain can be
      used to study quantitative changes of neurons, glial cells and capillary grid in
      the retinal ganglion layer of a single whole-mount retina. There is a remarkable
      degree of proportionality between the density of these cells over the whole
      normal retina.

PMID- 8740254
TI  - Retinal nitro blue tetrazolium staining and catalase activity in rat models of
      diabetes.
AB  - BACKGROUND: Recent studies have suggested that reactive oxygen species may be
      involved in the development of diabetic retinopathy. METHODS: Nitro blue
      tetrazolium (NBT) staining, a marker of reductants which may be induced by free
      radicals such as superoxide, and catalase activity, as an indirect measure of
      hydrogen peroxide (H2O2) generation, were studied in the rat retina in three
      conditions known to cause diabetes-like retinopathy, i.e. rats with spontaneous
      diabetes (the BB Wistar rat), rats with streptozotocin-induced diabetes mellitus,
      and rats fed on galactose. Male Wistar BB rats were studied 4-10 weeks after
      diagnosis of diabetes. Streptozotocin (60 mg/kg) was injected i.p. at 8 weeks of
      age and the experiments were performed after 8 weeks of diabetes. Young Sprague
      Dawley rats were fed a 50% galactose diet for 9, 12 or 22 months. RESULTS: In
      trypsinized vessel preparations, more intense NBT staining was observed only in
      rats fed a galactose diet for 22 months. In cross sections, the number of stained
      vessels were increased in BB rats (p < 0.01), but not in rats with streptozotocin
      induced diabetes. Catalase activity did not differ between any of the
      experimental groups and their matched controls. CONCLUSIONS: Increased amount of
      NBT reductants in retinal vessels occurred in BB Wistar rats and to some extent
      in galactose-fed rats, indicating a possible role for free radicals in the
      development of diabetic retinopathy. There was no evidence of increased retinal
      H2O2 production or activation of catalase, indicating that this particular enzyme
      was not affected during the conditions studied.

PMID- 8740255
TI  - Extraocular muscle changes in experimental orbital venous stasis: some
      similarities to Graves' orbitopathy.
AB  - BACKGROUND: Graves' orbitopathy (GO) is generally considered to have an
      autoimmune etiology. Recently, however, it has been hypothesized that orbital
      venous obstruction may contribute significantly to the clinical manifestations.
      To determine whether such obstruction could induce histologic and clinical
      findings consistent with GO, we developed an animal model of orbital venous
      obstruction by ligating the draining ophthalmic veins of the right eyes of four
      cats. METHODS: The branches of the ophthalmic veins were isolated and ligated
      following a lateral orbitotomy. Weekly photographs and echographs were taken of
      the cats; one cat was killed at each of four time points, namely 1, 2, 3, and 4
      weeks after surgery. Histologic stains were applied to isolated orbital tissues
      to characterize pathologic changes. RESULTS: Clinically, there was onset of
      marked proptosis, chemosis, and exotropia. Histological findings within the
      extraocular muscles included activation and the presence of acid
      mucopolysaccharides 1 week after ligation, increased collagen and the presence of
      lymphoid cells at 2 weeks after ligation, and persistent interstitial lymphocytic
      infiltrates the 3rd and 4th weeks after ligation. CONCLUSION: Without evoking a
      primary orbital inflammation or inducing a systemic autoimmune disease, an animal
      model has been developed that closely mimics many of the advanced clinical and
      histologic changes that occur in GO.

PMID- 8740256
TI  - Familial central serous retinopathy.
AB  - PURPOSE: To study the familial occurrence of central serous retinopathy (CSR).
      METHODS: We pooled data from eight eye clinics in Western Europe. RESULTS: We
      collected 11 families that each had two to four members with CSR. In 10 families
      siblings and in one family a mother and son were affected. Sixty percent of the
      patients were male and 40% female. CSR was found in 55 (92%) of 60 eyes, 44 (80%)
      showing a chronic course. In 25 patients (83%) both eyes were affected. Most
      recent visual acuity was 0.5 or less in 17 (39%) and 0.2 or less in 8 (18%) of
      the eyes with chronic CSR. CONCLUSION: Our findings of familial occurrence and a
      chronic disorder that is progressive, diffuse, and bilateral suggest an inborn
      disposition to develop a clinically manifest disintegration of the retinal
      pigment epithelium in adulthood.

PMID- 8740257
TI  - Possible changes in secondary structure and composition of human lens capsules in
      hereditary congenital cataract.
AB  - BACKGROUND: Scanty information is available on the changes in conformational
      structure and composition of human lens capsule in cases of hereditary congenital
      cataract. The purpose of this study was to use Fourier-transformed infrared (FT
      IR) spectroscopy to determine the secondary structure and composition of
      hereditary cataractous human lens capsule, as compared with normal human lens
      capsule. METHODS: FT-IR spectroscopy with the Fourier self-deconvolution and
      curve-fitting program was performed, and second-derivative analysis was used to
      verify the peak positions and assignments of the IR spectra. RESULTS: The curve
      fit FT-IR spectra revealed that the content of hydroxylysine and arginine were
      clearly higher in the lens capsule of the hereditary congenital patient, but the
      content of aspartic acid significantly lower, than in normal human lens capsules.
      The secondary conformational changes in alpha-helix, triple helix and random coil
      structures were important findings in the lens capsule of a hereditary
      cataractous patient. CONCLUSION: Possible alterations in secondary structures and
      compositions of lens capsule are observed in the hereditary congenital
      cataractous patient by using FT-IR spectroscopy with curve-fitting and second
      derivative analysis.

PMID- 8740258
TI  - Retinal and choroidal response to panretinal photocoagulation and ultrastructural
      perspective.

PMID- 8740259
TI  - Flow-cytometric investigation of epidermal cell characteristics in monogenic
      disorders of keratinization and their modulation by topical calcipotriol
      treatment.
AB  - A flow-cytometric study was performed in monogenic disorders of keratinization,
      to assess DNA distribution as well as the expression of keratins and involucrin.
      In addition, the changes in expression of these markers under influence of
      calcipotriol treatment were investigated. Proliferation, measured by the
      percentage of epidermal cells in SG2M-phase of the cell cycle, was increased in
      Darier's disease, lamellar ichthyosis, congenital bullous ichthyotic erythroderma
      of Brocq and the Comel-Netherton syndrome, whereas normal proliferation was found
      in autosomal dominant ichthyosis vulgaris, X-linked recessive ichthyosis,
      keratosis pilaris, ichthyosis bullosa of Siemens and the Sjogren-Larsson
      syndrome. Keratin 6 was enhanced in erythrodermic lamellar ichthyosis, congenital
      bullous ichthyotic erythroderma of Brocq and the Comel-Netherton syndrome,
      showing also reduction of keratin 10. Involucrin was only slightly reduced in
      erythrodermic lamellar ichthyosis, congenital bullous ichthyotic erythroderma of
      Brocq and the Comel-Netherton syndrome, compared to the pronounced reduction in
      all other skin disorders studied. Calcipotriol was found to enhance
      differentiation in Darier's disease, erythrodermic lamellar ichthyosis, and
      congenital bullous ichthyotic erythroderma of Brocq. Only Darier's disease did
      not show clinical improvement. In conclusion, flow cytometry provides a useful
      method for quantification of epidermal cell characteristics in monogenic
      disorders of keratinization. Further studies need to be performed to establish
      its usefulness as a diagnostic and prognostic tool.

PMID- 8740260
TI  - Inhibitory effect of vasoactive intestinal polypeptide and ketanserin on
      established allergic contact dermatitis in man.
AB  - Neuromediators may influence the immune response. To investigate their potential
      immunomodulating role in established allergic contact dermatitis in man, the
      following neuromediators were tested: vasoactive intestinal polypeptide (VIP),
      serotonin, and the serotonin antagonists ketanserin, methiotepine and ICS-205
      930. Positive patch test reactions were elicited by application of nickel
      sulphate for 48 h. The neuromediators were applied under patch test conditions
      after another 24 h. The test areas were measured before and 24 h after
      application of the neuromediators and biopsy specimens were taken for
      immunohistochemistry. After application of VIP at a concentration of 10(-5)
      mol/l, and of ketanserin at a concentration of 10(-4) mol/l, there was a
      significant reduction in the diameter of the test reaction. In addition, with VIP
      there was a reduction in the number of Leu 3a+ cells. Also tested was the
      influence of the neuromediators on the proliferative response of peripheral blood
      mononuclear cells from nickel-allergic subjects to nickel sulphate. The cells
      were cultured for 6 days and the neuromediators were added after 3 days. There
      was no effect on the proliferative response, except for slight inhibition by
      serotonin and by ketanserin at 10(-4) mol/l. More interferon gamma was found in
      the supernatants when VIP was added at 10(-5) and 10(-6) mol/l than in the
      control cultures. Thus, VIP and ketanserin may have an inhibitory effect on
      established allergic contact dermatitis. The effect of VIP is possibly mediated
      by an increased production of interferon gamma.

PMID- 8740261
TI  - Normolipidemic xanthelasma palpebrarum: lipid composition, cholesterol metabolism
      in monocyte-derived macrophages, and plasma lipid peroxidation.
AB  - The lipid compositions of 8 normolipidemic xanthelasma palpebrarum (XP) lesions
      were analyzed using thin-layer chromatography, with the adjacent uninvolved skin
      used as control. The lesions were found to be composed predominantly of
      cholesterol, mostly cholesteryl ester, whereas in the control specimens
      phospholipids predominated. The degradation rates of 125I-low-density lipoprotein
      (LDL), oxidized LDL, and acetyl LDL, and the rates of intracellular cholesterol
      synthesis from 1,2-(14)C-acetate, in blood monocyte-derived macrophages (MDM)
      from 3 normolipidemic patients, were similar to those of MDM from 3 normal
      control subjects. The mean levels of lipid peroxides and conjugated dienes under
      basal conditions, as well as following the addition of a free radical-generating
      compound (2,2-azobis-2-amidinopropane hydrochloride) to the plasma of 14
      normolipidemic XP patients were significantly higher than those of 14 age- and
      sex-matched normal controls. We conclude that the predominant lipid accumulated
      in normolipidemic XP lesions is cholesteryl ester, but there is no evidence for
      intrinsic cellular cholesterol metabolism derangement in blood MDM from patients
      which could account for this. Since macrophage cholesterol accumulation can also
      result from enhanced uptake of increased levels of oxidized LDL, the increased
      plasma lipid peroxidation (derived from oxidized LDL) might lead to accumulation
      of cholesterol in macrophages and formation of foam cells via this mechanism.

PMID- 8740262
TI  - A novel endogenous mediator of cutaneous inflammation: leukemia inhibitory
      factor.
AB  - Keratinocytes produce a variety of cytokines, including leukemia inhibitory
      factor. We hypothesised that this cytokine may play a pro-inflammatory role in
      the skin and tested this hypothesis by injecting recombinant leukemia inhibitory
      factor (1-100 ng) into the ear pinnae of C3H/HeJ mice. To other groups of
      animals, we injected boiled leukemia inhibitory factor or phosphate-buffered
      saline (negative control) or 0.4 ng human interleukin-1 alpha as a positive
      control. Following injection of 100 ng leukemia inhibitory factor, ear thickness,
      measured by micrometer, increased 66% over controls at 12 h and 100% at 24 h
      (overall p = 0.041 by analysis of variance). Injection of 0.4 ng interleukin-1
      alpha caused greater ear swelling. Compared with controls, swelling increased by
      67% at 6 h, 100% at 12 h and 340% after 24 h (overall p < or = 0.00001). Leukemia
      inhibitory factor (100 ng only) stimulated a 3.5-fold increase in leukocytes
      after 6 h. After 12 h, a 14-fold increase was seen in ears injected with 10 ng
      leukemia inhibitory factor and a 12-fold increase with 100 ng leukemia inhibitory
      factor, which remained elevated (17-fold) at 24 h (overall p = 0.0001). Injection
      of interleukin-1 alpha led to a 3.4-fold increase in leukocytes (mean per 20 high
      power fields) after 6 h, a 14-fold increase at 12 h and a 25-fold increase at 24
      h (overall p < or = 0.00001). These results demonstrate that leukemia inhibitory
      factor appears to be a mediator of cutaneous inflammation.

PMID- 8740263
TI  - Expression of heat shock protein 72 on peripheral blood mononuclear cells from
      patients with pustulosis palmaris et plantaris.
AB  - The expression of heat shock protein (HSP) 72 on peripheral blood mononuclear
      cells (PBMC) from patients with pustulosis palmaris et plantaris (PPP) was
      studied. PBMC isolated freshly from patients with PPP expressed HSP72, while
      those from psoriasis patients did not. PBMC from patients with PPP continued to
      express it in in vitro cultures at 37 degrees C. This expression was further
      augmented by in vitro heat stimulation at 43 degrees C. Immunofluorescence
      studies showed that approximately 20% of PBMC from patients with PPP were stained
      positively with anti-HSP72 antibody. HSP72 was expressed on both nonadherent and
      adherent cells of PBMC. These findings suggest that PBMC from patients with PPP
      may produce HSP72 spontaneously through their in vivo exposure to stressful
      agents.

PMID- 8740264
TI  - Role of adhesion molecules in the development of pustular lesions in patients
      with pustulosis palmaris et plantaris.
AB  - The expression of adhesion molecules and the ligands on endothelial cells and
      infiltrating inflammatory cells in lesional skin specimens from patients with
      pustulosis palmaris et plantaris was studied. Intercellular adhesion molecule-1
      and E-selectin were expressed on endothelial cells of microvessels in the
      papillary dermis. Intercellular adhesion molecule-1 was also expressed focally on
      keratinocytes in the epidermis of the lesional skin. On the other hand,
      lymphocyte function-associated antigen-1, Mac-1 and sialyl Lewis(x) were
      expressed on infiltrating inflammatory cells. Further, flow cytometric analysis
      demonstrated that circulating leukocytes in peripheral blood from patients with
      pustulosis palmaris et plantaris expressed the ligands of adhesion molecules. It
      is therefore suggested that the expression of adhesion molecules and the ligands
      on circulating leukocytes, endothelial cells, infiltrating inflammatory cells and
      keratinocytes might be closely related to the formation of pustular lesions in
      patients with pustulosis palmaris et plantaris.

PMID- 8740265
TI  - Increased degradation of type I collagen in acne fulminans.
AB  - Acne fulminans is a rare, severe type of acne with unknown etiology. Ulcerative
      acne lesions, fever and musculoskeletal pain are typical symptoms. In addition,
      osteolytic or even destructive osteomyelitis-like bone lesions occur in many
      patients with acne fulminans. In the present study the degradation product (ICTP)
      of type I collagen, the most abundant collagen of the skeleton, was measured from
      the sera of patients suffering from acne fulminans. In 3 of 4 acne fulminans
      patients with active disease, the ICTP concentrations were clearly higher than
      the range of concentrations in age-matched controls. The mean concentration of
      ICTP in the acne fulminans patients was 17.6 +/- 6.0 micrograms/I, whereas the
      corresponding concentration in 6 patients with severe nodular acne was 6.9 +/-
      2.1 micrograms/I. Increased uptake of radionuclide in bone scans was observed in
      all of the 4 patients with acne fulminans. The present results suggest that ICTP
      is increased in acne fulminans, due to the destruction of bone collagen matrix.
      ICTP could thus be used for monitoring the activity of acne fulminans affecting
      the skeleton.

PMID- 8740266
TI  - Occurrence and distribution of peptidergic nerve fibers in skin biopsies from
      patients with systemic sclerosis.
AB  - Systemic sclerosis is characterized by vascular dysfunction. Itch is sometimes
      present in early stages of the disease. This prompted us to study the innervation
      of the skin by immunocytochemistry. Antibodies to neuropeptide Y and vasoactive
      intestinal peptide were used for autonomic nerves. Sensory innervation was
      studied using antibodies to substance P and calcitonin gene-related peptide.
      Protein gene product 9.5 was used as a general neuronal marker. Skin biopsies
      from affected (lower arm) and non-affected (upper back) sites on 10 patients with
      systemic sclerosis and from corresponding sites on 10 sex- and age-matched
      healthy controls were studied. Regional variations were found in the occurrence
      of peptidergic nerve fibers. In the patients the density of nerve fibers
      (measured semiquantitatively) stained by the panneuronal marker was lower in
      affected than in unaffected skin (p < 0.05). There were no significant
      differences in peptidergic innervation between patients and controls. However,
      there was a tendency to higher density of neuropeptide Y-positive nerve fibers in
      the forearm skin in 6 to 10 patients, as compared to only 1 of 10 healthy
      controls.

PMID- 8740267
TI  - Effects of topical application of capsaicin to human skin: a comparison of
      effects evaluated by visual assessment, sensation registration, skin blood flow
      and cutaneous impedance measurements.
AB  - A new non-invasive device, which enables local measurements of electrical
      impedance, has been used to evaluate the degree of irritation in human skin. The
      results have been compared with visual scoring, sensations and laser Doppler
      flowmetry. Capsaicin (50 microliters 1% solution) and control solutions (50
      microliters 50% ethanol) were applied in a chamber for 30 min on the volar
      forearm of 7 volunteers. Values were recorded before application and during the
      total test period of 4.5 h. Sensations like sting/prick, burn and pain were
      produced by this treatment, and the flare response was observed. Using the non
      invasive laser Doppler flow technique to measure blood flow in human skin, we
      have shown that topical application of capsaicin abolishes the vasodilator
      response to local heat provocation (40 degrees C). There was close agreement
      among values obtained using visual assessments, sensations and laser Doppler
      flowmetry. Results obtained using electrical impedance measurements were not
      consistent with the other three methods.

PMID- 8740268
TI  - A case of actinic granuloma associated with periumbilical perforating
      pseudoxanthoma elasticum.
AB  - We report an unusual case of actinic granuloma of the face and periumbilical
      perforating pseudoxanthoma elasticum located superior to the umbilicus in a 57
      year-old Korean woman. Histopathologically, these two dermatoses have a similar
      degeneration of elastic fibers, but they show different host reactions to the
      altered elastic fibers. In the actinic granuloma, actinically damaged elastic
      fibers were followed by granulomatous infiltration on the sun-exposed area, while
      in the perforating pseudoxanthoma elasticum, the altered elastic fibers induced a
      foreign body reaction, with subsequent transepidermal elimination. This is the
      first case report showing both actinic granuloma and periumbilical perforating
      pseudoxanthoma elasticum in the same patient, which suggests that the basic
      mechanism eliciting these dermatoses is similar.

PMID- 8740269
TI  - The Allergen Bank: a source of extra contact allergens for the dermatologist in
      practice.
AB  - The Allergen Bank was established to give dermatologists easy access to special
      test materials in order to make early diagnoses of special cases of allergic
      contact dermatitis. The Allergen Bank comprises a computer system to register
      several hundred contact allergens in appropriate patch test concentrations
      available at the allergy laboratory and the patch test results. At the request of
      dermatologists in practice for Allergen Bank may supply special contact allergens
      for aimed patch testing of contact dermatitis patients. The organization of the
      Allergen Bank and the procedure of its use are described. During its first 23
      months 28 dermatologists asked for 2,209 allergen samples for testing of 386
      patients, an average of 6 allergens per patient and 14 patients per
      dermatologist. A total number of 164 positive reactions have been registered, and
      440 of the 540 allergens have been in use. One third of the positive reactions
      were caused by the 16 most frequently ordered allergens, which amounted to 340
      allergen samples. The allergens included plant chemicals, acrylates, animal feed
      additives, fragrance chemicals and preservatives. Selected allergens were
      investigated for stability during handling and shipping under varying conditions
      relevant to the function of the Allergen Bank. The possible inhomogeneity of
      petrolatum based allergen preparations is discussed in relation to diagnostic
      patch testing.

PMID- 8740270
TI  - Generalized morphea with vascular involvement. A case report and disaccharide
      analysis of the skin glycosaminoglycans.
AB  - We report a 69-year-old man with severe generalized morphea, who showed over 80%
      of skin involvement, while the internal organs were not affected. We performed
      histological examinations and analysis of skin disaccharides constituting
      chondroitinase-digestible glycosaminoglycans in the center and periphery of the
      sclerotic lesions and the clinically uninvolved skin. In both the central and
      peripheral parts of the sclerotic lesions, sclerotic fibrosis and a dense
      perivascular cell infiltration, consistent with morphea, were seen in the entire
      dermis and subcutis. Furthermore, various vascular changes were observed, such as
      endothelial cell swell, thickened basement membrane and obstruction of vascular
      lumen in the fat lobules. In the clinically uninvolved skin, interstitial edema
      was prominent along with a slight perivascular cell infiltration. On disaccharide
      analysis, the increase in the amount of delta Di-4S(DS), the main disaccharide
      unit of dermatan sulphate, delta Di-6S and delta Di-6S, the main disaccharide
      units of chondroitin sulphate, and the decrease in delta Di-HA, which is derived
      from hyaluronate, were found not only in the sclerotic lesions but also in the
      clinically uninvolved skin, though less prominent. These alterations were
      consistent with systemic sclerosis, suggesting a close relationship between
      severe forms of generalized morphea and systemic sclerosis.

PMID- 8740271
TI  - Clinical aspects of the use of gamma linolenic acid in systemic sclerosis.
AB  - Systemic sclerosis is a multi system disorder, for which there is no satisfactory
      treatment. Theoretically, dietary supplementation with essential fatty acids may
      lead to an increase in their derivatives, the vasoactive prostaglandins, which
      benefit the acute and chronic ischaemic lesions of this disease. We assessed the
      value of concentrated essential fatty acids in patients with systemic sclerosis,
      concentrating particularly on vascular symptoms and objective tests of vascular
      reactivity. Twenty-five patients with systemic sclerosis were randomised to
      receive concentrated essential fatty acids or placebo, for 6 months in a double
      blind parallel group study. There was no significant difference between the
      active and placebo groups in terms of maximum blood flow after warming, minimum
      blood flow after cooling or the recovery time after cooling. There were no
      significant differences between the groups in the other parameters measured.
      Dietary essential fatty acids have no role in the treatment of vascular symptoms
      in established systemic sclerosis.

PMID- 8740272
TI  - Sexually transmitted diseases and risk of HIV infection.
AB  - We have analyzed the association between sexually transmitted diseases (STD) and
      HIV infection, using data from a cross-sectional survey of subjects attending STD
      clinics in Northern Italy conducted since 1988. A total of 1,711 subjects (1,259
      males, 452 females), who had referred themselves to three STD clinics in Northern
      Italy for suspected STD or STD treatment, were included for the study. Out of
      these, 145 subjects (113 males and 32 females) were HIV-positive. A total of 58
      HIV-positive and 368 HIV-negative subjects reported a history of STD; the
      corresponding odds ratio (OR) was 2.3 (95% confidence interval (CI) 1.5-3.6) for
      subjects reporting a history of STD. Considering various STD in details, the
      estimated OR was 1.8 (95% CI 0.8-3.8) for a history of gonorrhoea and 1.5 (95% CI
      0.8-2.7) of syphilis, and the OR was 1.8 (95% CI 1.0-3.2) and 2.2 (95% CI 1.3
      3.8), respectively, for a positive TPHA and VDRL test. The results of the test
      for HbsAg were available in 50 HIV-positive and 1,028 HIV-negative subjects; the
      OR of HIV infection in subjects with HbSAg was 3.9 (95% CI 1.7-9.0). Presence of
      genital ulcers at clinical examination was not significantly associated with the
      risk of HIV infection (OR yes vs no genital ulcers 1.5, 95% CI 0.6-2.8).

PMID- 8740273
TI  - Casual sex, extramarital sex, condom use and alcohol intake among heterosexual
      patients attending an STD clinic in Norway.
AB  - A study excluding homosexuals was performed to study casual sex, extramarital
      sex, the use of a condom with a casual sexual partner and the combination of
      alcohol intake and casual sex among patients attending a clinic for sexually
      transmitted diseases (STDs). Heterosexual patients (467) received a
      questionnaire, and 458 were included. Men reported more (94%) casual sexual
      partners than did women (76%). According to a multiple logistic regression
      analysis a condom was used significantly less frequently in "old" respondents,
      those having a permanent sexual partner, those having low education, those
      infected with STDs (earlier STDs), those who had had more than 4 sexual partners
      over the last year, and those combining alcohol intake and casual sex.
      Intravenous drug users/prostitutes used a condom more often than did men with
      paid sex and "other heterosexuals". To have an effect on STD patients, innovative
      forms of health education may be necessary, and greater emphasis should be placed
      on more informal means of information, including interactive health education and
      communication strategies to promote positive attitudes regarding condom use.

PMID- 8740274
TI  - Lichen ruber planus following the administration of human anti-hepatitis B virus
      immunoglobulins.

PMID- 8740275
TI  - Treatment of lipoid proteinosis with etretinate.

PMID- 8740276
TI  - Sporadic unilateral intra-areolar polythelia. Report of an additional case and
      review of the literature.

PMID- 8740277
TI  - Hailey-Hailey disease with acrokeratosis verruciformis Hopf.

PMID- 8740278
TI  - Burning mouth syndrome: hypersensitivity to sodium metabisulfite.

PMID- 8740279
TI  - Herpes zoster-associated trigeminal neurotrophic ulcer.

PMID- 8740280
TI  - Treatment of lichen simplex chronicus with topical capsaicin cream.

PMID- 8740281
TI  - A case of atypical localized scleroderma presenting with pseudoainhum: treatment
      with tranilast, an anti-fibrotic agent.

PMID- 8740282
TI  - Contact dermatitis after calcipotriol and patch test evaluation.

PMID- 8740283
TI  - Anaphylactoid symptoms due to oral minocycline.

PMID- 8740284
TI  - Acquired zosteriform naevus flammeus: a cutaneous marker of central nervous
      system angiomatosis.

PMID- 8740285
TI  - Chloroquine-induced vitiligo. A case report and review of the literature.

PMID- 8740286
TI  - Bullous scabies.

PMID- 8740287
TI  - A case of Neumann type pemphigus vegetans showing reactivity with the 130 kD
      pemphigus vulgaris antigen.

PMID- 8740288
TI  - Is EMLA effective in Dercum's disease?

PMID- 8740289
TI  - Cutaneous leishmaniasis. an old disease with a new face.

PMID- 8740290
TI  - Extramammary Paget's disease of the axilla with an underlying apocrine carcinoma.

PMID- 8740291
TI  - Plasma exchange in childhood Guillain-Barre syndrome.

PMID- 8740292
TI  - Prediction and non-invasive assessment of neonatal jaundice in the term healthy
      newborn infant.
AB  - The maternal and umbilical cord bilirubin concentration at delivery, a yellow
      skin colour on the first postnatal day, an increase in the yellow skin colour
      during the first 24 h or postnatal life, and carbon monoxide excretion are all
      associated with the later development of neonatal jaundice in the healthy, mature
      newborn infant. Based on the results from these methods, and especially when the
      results from two or more of the methods are combined, it is possible to define
      low- and high-risk groups as far as subsequent jaundice is concerned. If jaundice
      develops, yellow skin colour measurements can often replace plasma bilirubin
      determinations. Dependent upon the local current consensus for bilirubin
      determinations, around 50% of plasma bilirubin determinations can be avoided.
      Recent research suggests that yellow skin colour measurements may provide
      information concerning the risk of bilirubin encephalopathy, in addition to their
      relation to the plasma bilirubin concentration.

PMID- 8740293
TI  - GH treatment in neonates.

PMID- 8740294
TI  - SIDS or not SIDS? Classification problems of sudden infant death syndrome.

PMID- 8740295
TI  - Psychological long-term coping with experience of disease and treatment in
      childhood cancer survivors.

PMID- 8740296
TI  - Correlation of toddlers' serum lipoprotein(a) concentration with parental values
      and grandparents' coronary heart disease: the STRIP baby study.
AB  - The correlation between lipoprotein(a) (Lp(a)) concentrations in children aged 7
      24 months and their family members was determined and the association between the
      Lp(a) values of the children and a family history of coronary heart disease (CHD)
      was assessed. The Lp(a) values of the children correlated strongly with midparent
      Lp(a) values as early as at 7 months of age (r = 0.54 to 0.59, p < 0.0001). This
      correlation was stronger than the correlation of serum total cholesterol and
      total cholesterol corrected for Lp(a)-cholesterol between children and parents.
      None of the parents had CHD. The median Lp(a) concentration of the parents with a
      family history of CHD was significantly higher than that of parents with no such
      history (111 vs 87 mg/1, p = 0.024). However, the children's Lp(a) levels were
      not associated with CHD in their grandparents. The genetic dependence of the
      Lp(a) concentration is already evident in infancy. The Lp(a) concentration in
      young parents, but not in their 24-month-old children, is associated with CHD in
      grandparents. This may be explained by a dilution of the genetic influence on
      Lp(a) over two generations.

PMID- 8740297
TI  - A regression method including chronological and bone age for predicting final
      height in Turner's syndrome, with a comparison of existing methods.
AB  - A total of 235 measurement points of 57 Dutch women with Turner's syndrome (TS),
      including women with spontaneous menarche and oestrogen treatment, served to
      develop a new Turner-specific final height (FH) prediction method (PTS).
      Analogous to the Tanner and Whitehouse mark 2 method (TW) for normal children,
      smoothed regression coefficients are tabulated for PTS for height (H),
      chronological age (CA) and bone age (BA), both TW RUS and Greulich and Pyle (GP).
      Comparison between all methods on 40 measurement points of 21 Danish TS women
      showed small mean prediction errors (predicted minus observed FH) and
      corresponding standard deviation (ESD) of both PTSRUS and PTSGP, in particular at
      the "younger" ages. Comparison between existing methods on the Dutch data
      indicated a tendency to overpredict FH. Before the CA of 9 years the mean
      prediction errors of the Bayley and Pinneau and TW methods were markedly higher
      compared with the other methods. Overall, the simplest methods--projected height
      (PAH) and its modification (mPAH)--were remarkably good at most ages. Although
      the validity of PTSRUS and PTSGP remains to be tested below the age of 6 years,
      both gave small mean prediction errors and a high accuracy. FH prediction in TS
      is important in the consideration of growth-promoting therapy or in the
      evaluation of its effects.

PMID- 8740298
TI  - Linear growth of very young asthmatic children treated with high-dose nebulized
      budesonide.
AB  - The aim of this open study was to observe linear growth in young children with
      asthma treated with nebulized budesonide. Infants and young children (< 3 years
      old) with severe uncontrolled asthma were studied. They were treated with
      nebulized budesonide (1-4 mg day-1) and treated for at least 6 months. Height
      standard deviation scores (HtSDS) were measured before ("pre-measurements")
      immediately prior to commencing nebulized budesonide therapy (baseline) and after
      at least 6 months of therapy ("post-measurements"). The mean HtSDS score at
      pretreatment was -0.21 and at baseline had fallen further to -0.46. The mean
      HtSDS increased to -0.17 when the post-measurements were made (p = 0.035) after
      at least 6 months of nebulized budesonide therapy. Treatment with nebulized
      budesonide for longer than 6 months in very young children with severe asthma was
      not associated with reduced linear growth.

PMID- 8740299
TI  - Sustained attention problems in children with early treated congenital
      hypothyroidism.
AB  - Sustained attention was studied in 48 children with early treated congenital
      hypothyroidism and 35 healthy controls, using a computer-paced and a self-paced
      continuous performance task. The performance of the patients, particularly those
      in the low T4 group (38 patients with T4 levels < 50 nmol/l at neonatal
      screening), declined in the final stage of the computer-paced task, suggesting a
      problem in remaining attentive over time. The performance of all children
      declined in the first and improved in the final stage of the self-paced task.
      This pattern was most pronounced in the low T4 group, reflecting greater
      variability in their task performance over time, again indicating a problem in
      sustaining attention. No correlation was found between onset of treatment and
      sustained attention. The small size of the intermediate T4 group (10 patients
      with T4 levels > or = 50 nmol/l at neonatal screening) made the results more
      difficult to interpret and may have concealed a problem with sustained attention
      in this group.

PMID- 8740300
TI  - Early 99mTc dimercaptosuccinic acid (DMSA) scintigraphy in symptomatic first-time
      urinary tract infection.
AB  - During a 2 year period, 175 children below 6 years of age (median 0.4 year) with
      non-obstructive symptomatic urinary tract infection were studied by 99mTc
      dimercaptosuccinic acid (DMSA) scintigraphy. DMSA scintigraphy was performed at a
      median of 10 days after the start of treatment and was abnormal in 73 children
      (42%), equivocal in 29 (16%) and normal in 73 (42%). Reflux was seen in 27% of
      all children and in 38% of the renal units that were abnormal at DMSA
      scintigraphy. A decreasing frequency of abnormalities at DMSA scintigraphy was
      seen within the first 14 days after the start of treatment. C-reactive protein
      and grade of reflux correlated significantly with abnormal DMSA studies. To
      demonstrate renal involvement in acute urinary tract infection, DMSA scintigraphy
      should be performed within days after the start of treatment. It is noteworthy
      that reflux was seen in less than half of renal units with abnormal DMSA
      scintigraphy.

PMID- 8740301
TI  - Autosomal recessive polycystic kidney disease in 115 children: clinical
      presentation, course and influence of gender. Arbeitsgemeinschaft fur
      Padiatrische, Nephrologie.
AB  - The clinical course of 66 boys and 49 girls with autosomal recessive polycystic
      kidney disease recruited from departments of paediatric nephrology was
      investigated over a mean observation period of 4.92 years. This is a selected
      study group of children from departments of paediatric nephrology who in most
      cases survived the neonatal period, since birth clinics did not participate. The
      median age at diagnosis was 29 days (prenatal to 14.5 years). We observed
      decreased glomerular filtration rates (GFRs) in 72% (median age at onset of
      decrease of GFR < 2 SD, 0.6 years; range, 0-18.7 years), and 11 patients
      developed end-stage renal disease. Hypertension requiring drug treatment was
      found in 70% (median age at start of medication, 0.5 years; range, 0-16.7 years).
      Kidney length was above the 97th centile in 68% of patients, and kidney length
      did not increase with age or deterioration of renal function. Urinary tract
      infections occurred in 30%, growth retardation in 25%, and clinical signs of
      hepatic fibrosis were detected in 46%. Thirteen patients (11%) died during the
      observation period, 10 of them in the first year of life. There was a
      statistically significant sex difference in terms of a more pronounced
      progression in girls. The survival probability at 1 year was 94% for male
      patients and 82% for female patients (p < 0.05) in this study. Urinary tract
      infections occurred more frequently in girls (p < 0.025) and were observed
      earlier. In addition, more girls had impaired renal function, developed end-stage
      renal disease and showed growth retardation; these differences, however, were not
      significant. For the children in this study, however, our results indicate that
      the long-term prognosis in the majority of cases is better throughout childhood
      and youth than often stated.

PMID- 8740302
TI  - The effect of carnitine supplementation in valproate-induced hyperammonaemia.
AB  - The aim of the study was to investigate the effect of carnitine supplementation
      of valproic acid (VPA) treated patients presenting with increased plasma ammonia
      concentrations. Plasma ammonia concentrations were recorded in 69 children and
      young adults on VPA monotherapy (25.6 +/- 9.2 mg VPA/kg per day; mean plasma VPA
      concentration 68.8 +/- 27.6 mg/l). Their mean plasma ammonia concentration was
      80.2 +/- 32.1 micrograms/dl (median 73.1 microgram/dl). A total of 24 patients
      (35.3%) presenting with ammonia concentrations > 80 microgram/dl were considered
      hyperammonaemic. Of these, 15/24 (22.1%) showed ammonia concentrations > 100
      microgram/dl, even up to 194 micrograms/dl. In 48/69 patients, plasma carnitine
      concentrations could be determined. The plasma total carnitine (TC)
      concentrations were rather low (26.9 +/- 8.8 mumol/1) compared to normal values
      obtained in our laboratory (40.9 +/- 7.2 mumol/1). The percentage of free
      carnitine was considered decreased (< 75% TC) in 13/48 samples (27%). Fourteen
      hyperammonaemic patients and one with a plasma ammonia level of 60 micrograms/dl
      agreed to be supplemented with L-carnitine (1 g/m2 per day divided into two equal
      doses). Their plasma ammonia and carnitine concentrations were re-evaluated after
      a mean of 9.1 +/- 4.0 days (median 9.0 days) and in 9 patients again after a mean
      of 79.6 +/- 30.1 days (median 75 days) of L-carnitine supplementation. Plasma
      ammonia concentrations decreased in all 15 patients. The decrease was 25.4 +/-
      11.2% (median 28.3%) after a mean of 9.1 +/- 4.0 days and amounted to 46.0 +/-
      17.2% (median 48%) after 79.6 +/- 30.1 days. L-Carnitine supplementation led to
      an increase in plasma free carnitine of 11.6 +/- 13.0% (median 15.6%) and to a
      further increase of 11.1 +/- 8.4% (median 11.5%) when re-evaluated a second time.
      The plasma ammonia concentrations were significantly correlated with the
      percentage of free plasma carnitine (r = -0.67; p < 0.0001). The results show
      that carnitine supplementation is a means of normalizing elevated plasma ammonia
      concentrations. However, we cannot conclude from our results whether this lowers
      the risk of developing a VPA-induced Reye's-like syndrome.

PMID- 8740303
TI  - Magnetic resonance imaging and neurological evaluation after treatment with high
      dose methotrexate for acute lymphocytic leukaemia in young children.
AB  - This study evaluates the occurrence of permanent cerebral white matter changes
      and neurological abnormalities in children treated at a young age for acute
      lymphocytic leukaemia. Our pilot treatment protocol did not include central
      nervous system irradiation, but intrathecal methotrexate and high-dose
      methotrexate infusions followed by very intensive folinic acid rescue. We
      examined 12 children in complete remission and off therapy 18 months to 9.5 years
      after their last methotrexate infusion. They were below 5 years of age at
      diagnosis and therefore expected to be at special risk of neurotoxic sequelae.
      Cerebral magnetic resonance imaging in the 11 cases thus evaluated did not reveal
      white matter abnormalities or other signal changes as signs of permanent
      treatment-related sequelae. We did not observe any pathological clinical
      neurological findings likely due to methotrexate.

PMID- 8740304
TI  - Infantile colic--less common than previously estimated?
AB  - A two-part population-based study investigating the occurrence of infantile colic
      was undertaken, in which 92% of mothers with newborn healthy infants were
      reached. In the prospective part 152 mothers ("diary group") registered crying
      and fussing in their infants during 12 weeks. In the retrospective part 224
      mothers ("interview group") were contacted by telephone at an infant age of 5-7
      months. The colic occurrence was determined according to four different
      definitions; the rate varied from 3.3 to 17.1%. The classical "Wessel-type" colic
      was present in 9.3%. Colic defined as "crying seen as a problem by parent" was
      present in 12.1% of the "interview group", but in only 3.3% of the "diary group".
      Some earlier studies may have overestimated colic occurrence. Another possibility
      is an actual decline. The contributive part of preventive measures is discussed.

PMID- 8740305
TI  - Early childhood appendicitis is still a difficult diagnosis.
AB  - We report on 90 pre-school children operated on for suspected acute appendicitis.
      The data analysis was retrospective. The outcome of exploration was negative in
      54% (49/90) of cases; inflamed nonperforated appendix was removed 28% (25%/90)
      and a perforated appendix in 18% (16/90) of cases. In infants aged < 3 years (n =
      26) the perforation rate was 60%, and in children age 4-5 years (n = 64) it was
      27%. Tenderness in the iliac fossa, blood leukocytosis and urinanalysis had
      little diagnostic value. Preoperative signs of diffuse peritonitis and elevated
      values of serum C-reactive protein were found more frequently only in the
      children with a perforated appendix. There was no mortality and the postoperative
      morbidity varied between 10 and 20%. Thus, although appendectomy is currently a
      safe procedure in children, more specific non-invasive diagnostic acids are still
      needed to reduce the number of negative explorations and the rate of perforation.

PMID- 8740306
TI  - Infant fussing and crying patterns in the first year in an urban community in
      Denmark.
AB  - Infant crying amounts and patterns in 590 1- to 12-month-old infants in an urban
      community in Denmark were studied using the Crying Patterns Questionnaire. The
      impact of the crying on parents and the primary health services was also
      assessed. The results showed that Danish mothers leave their infants to "cry out"
      substantially less than mothers in the UK and North America. Despite this
      difference, mean crying amounts, crying patterns and the incidence of persistent
      crying were similar to those reported in earlier western studies. The findings
      support the view that the infant crying peak in the first 3 months is due to
      normal maturational and developmental processes.

PMID- 8740307
TI  - Irregular breathing in young lambs and newborn infants during heat stress.
AB  - Ten healthy unanaesthetized full-term lambs, aged 4-12 days, were studied during
      moderate radiant heat stress, and 21 full-term newborn infants were studied
      during moderate convective heat stress. The rate of breathing and the breathing
      pattern were recorded, using strain gauges made of mercury-filled rubber tubing
      placed around the thorax and abdomen. In both the lambs and the infants the
      respiratory rate increased during heat stress. When this increase began, both the
      lambs and infants had short periods of very rapid breathing followed by short
      apnoeas. The concentrations of carbon dioxide and water in a flow-through system
      collecting expired air increased during the short periods of rapid breathing and
      then decreased again during the subsequent short apnoeic period.

PMID- 8740308
TI  - Crying in separated and non-separated newborns: sound spectrographic analysis.
AB  - During the first 1-2 h after birth crying occurs during separation from the
      mother and stops on reunion. In rats, such "separation distress calls" have
      distinct phonetic properties. We examined this early crying by sound
      spectrography in 29 healthy, full-term, vaginally delivered babies, randomly
      assigned either to be kept in a cot or to be placed in body contact with the
      mother during the 90 min following birth. The former babies cried almost 10 times
      more than the latter ones. The duration of the cry signal (the smallest element
      of a cry analysed by spectrography) in both groups was 0.8-09s; the melody
      contour was flat or slightly rising--falling with a fundamental frequency of
      around 500 hertz. The cry is provisionally characterized as a discomfort cry,
      elicited mainly by separation from the mother.

PMID- 8740309
TI  - Effects of recombinant human growth hormone treatment in intrauterine growth
      retarded preterm newborn infant on growth, body composition and energy
      expenditure.
AB  - The effects of recombinant human growth hormone treatment during the early
      postnatal period on growth, body composition and energy expenditure were studied
      in seven intrauterine growth-retarded newborns. Seven infants were studied as
      controls. No differences were seen in bodyweight or height gain (15.9 +/- 1.5
      g/kg per day and 1.02 +/- 0.24 cm/week in the treated and 16.3 +/- 1.4 g/kg per
      day and 1.11 +/- 0.30 cm/week in the control group). Skinfold growth rate was
      0.52 +/- 0.20 mm/week in the treated vs. 0.56 +/- 0.28 mm/week in the control
      group. Total body water (as a percentage of bodyweight, 80 +/- 3.0% vs. 80 +/-
      4.0%) and energy expenditure (67.5 +/- 7.4 vs. 66.7 +/- 6.4kcal/kg per day) using
      2H2 18O showed identical results in both groups. We conclude that the recombinant
      human growth hormone treatment directly after birth in intrauterine growth
      retarded newborn infants results neither in an increase in growth rate nor a
      change in body composition or energy expenditure during the early postnatal
      period.

PMID- 8740310
TI  - Infection with Ureaplasma urealyticum and Mycoplasma hominis and the development
      of chronic lung disease in preterm infants.
AB  - In a prospective cohort study in a tertiary referral neonatal intensive care
      unit, the endotracheal secretions of 40 consecutively intubated newborn infants,
      less than 31 weeks' gestation, were examined weekly for the genital mycoplasmas
      and all other common bacterial pathogens. Fifteen (37%) infants were positive for
      Ureaplasma urealyticum and/or Mycoplasma hominis. There were no differences in
      gestation, birthweight, use of surfactant, or time on ventilator between the
      culture-positive and negative babies. Thirteen (87%) of the culture-positive
      group developed chronic lung disease (CLD) compared with 11 (41%) of the negative
      group (p = 0.0196). Of those culture-positive, 37% were not identified on the
      first specimen taken at the time of admission. These data suggest a significant
      association between infection with the urogenital mycoplasma and CLD and also
      stress the need for repeated cultures to identify these organisms.

PMID- 8740311
TI  - Glial fibrillary acidic protein is increased in the cerebrospinal fluid of
      preterm infants with abnormal neurological findings.
AB  - Glial fibrillary acidic protein (GFAP) is the structural protein of the
      intermediate filament of astroglia. The aims of the present study were to examine
      GFAP in the cerebrospinal fluid (CSF) of preterm infants at different
      postmenstrual ages and to evaluate the potential of GFAP to predict abnormal
      neurodevelopmental outcome. GFAP increased in correlation with postmenstrual age
      in preterm infants (n = 17) and full-term infants (n = 9). The levels were five
      times higher in preterm infants (n = 10) with an abnormal neonatal course and/or
      an abnormal neurological outcome than in healthy preterm infants. The positive
      predictive value of a GFAP higher than the 98th percentile of normal infants was
      69%, while a GFAP level below this limit invariable predicted a good outcome.
      Simultaneously analysed noradrenaline, hypoxanthine and glutamate did not differ
      between the groups. We conclude that CSF GFAP increases with maturity and that
      CSF GFAP appears to be a promising marker for perinatal brain damage.

PMID- 8740312
TI  - Erythropoietin (Epo), protein and iron supplementation and the prevention of
      anaemia of prematurity: effects on serum immunoreactive Epo, growth and protein
      and iron metabolism.
AB  - The effect of recombinant human (r-Hu) erythropoietin (Epo) (300 IU/Kg per week
      for 4 weeks) was studied in healthy preterm infants (n = 14) fed human milk with
      additional milk protein and high doses of iron. The controls (n = 15) were in
      themselves a study group and were used to follow the natural course of anaemia of
      prematurity on such nutrition. Serum immunoreactive Epo (SiEpo) increased
      significantly 24 h after r-HuEpo injections (range 36 to > 128 mU/ml) and
      remained at these levels throughout the treatment period. r-HuEpo in such
      moderate doses kept haemoglobin above 11 g/dl. Bodyweight gain, protein and iron
      parameters indicated adequacy of dietary protein and iron. In controls, siEpo
      increased during the first weeks after nutritional supplementation, with a
      concommitant rise in reticulocyte count. At age 3 weeks, despite low siEpo
      levels, reticulocyte counts indicated active erythropoiesis. Following further
      moderate increases in siEpo, the reticulocyte count increased to high levels
      (7%). The reticulocyte response suggests that erythropoiesis in preterm infants
      is less dependent upon Epo levels than in adults.

PMID- 8740313
TI  - Decreased ferritin levels, despite iron supplementation, during erythropoietin
      therapy in anaemia of prematurity.
AB  - Erythropoietin (rHuEPO) therapy has been shown to be beneficial in preventing and
      treating anaemia of prematurity and to decrease the need for blood transfusions.
      There is, however, only scanty data on the effect of rHuEPO therapy on iron
      metabolism. We studied 29 preterm infants (age 34 +/- 14 days) who were randomly
      assigned to receive either rHuEPO 900 U kg-1 week-1 with 6 mg kg-1 day-1 of iron
      for 4 weeks (n = 15) or no therapy. The following parameters were evaluated and
      compared between and within groups at the beginning, during and at the end of the
      study: Haematocrit (SI), reticulocytes (10(9) micrograms l-1), serum ferritin
      (microgram 1-1) and iron (mumol l-1). The results were as follows. At the
      baseline, erythropoietin levels were similar in both groups: 7.2 +/- 5.6 versus
      6.2 +/- 3.2 mU ml-1 (NS). In the treated infants the haematocrit remained stable
      during the study and was significantly higher than in the control group by the
      end of the study: 0.34 +/- 0.03 versus 0.28 +/- 0.05 (p = 0.001). rHuEPO therapy
      increased the reticulocyte count from 130 +/- 70 to 430 +/- 200 (p = 0.0002).
      However, rHuEPO therapy depleted both serum ferritin and iron levels from 321 +/-
      191 to 76 +/- 58 micrograms l-1 (p = 0.04) and from 18 +/- 5 to 13 +/- 4 mumol l
      1 (p = 0.03), respectively. We conclude that rHuEPO therapy prevented anaemia and
      its sequelae; however, serum ferritin and iron levels were depleted. We suggest
      that the effect of rHuEPO may be further increased by higher iron
      supplementation.

PMID- 8740314
TI  - Intralesional steroids in Langerhans cell histiocytosis of bone.
AB  - Langerhans cell histiocytosis may involve single or multiple organ systems. Bone
      involvement is the most common feature. We have examined retrospectively the
      effects of 20 intralesional injections of steroids into bone in seven patients
      seen at our department from 1988 to 1993. Most of these injections (75%) relieved
      the symptoms, and no side-effects were observed. However, injections into the jaw
      were seldom effective. Our results suggest that the dose of the steroids
      administered is of importance.

PMID- 8740315
TI  - Ventilator-associated sinus arrhythmia in a preterm neonate--an indicator for a
      mature autonomic nervous system?
AB  - According to control theory, the interactions between respiration and heart rate
      (i.e. respiratory sinus arrhythmia, RSA, and breath amplitude sinus arrhythmia,
      BASA) reflect the inner workings of the physiological control systems of
      respiration and circulation. This paper reports on a preterm neonate (28.5 weeks
      old, 940 g) who showed the presence of ventilation-associated sinus arrhythmia
      (VASA) under moderate artificial ventilation. His heart rate variability was
      entrained to the ventilatory stimulus. VASA and entrainment suggest that the
      parasympathetic part of the autonomic nervous system might be more mature than
      expected in some preterm neonates.

PMID- 8740316
TI  - Temporary intrathoracic adenopathy in children--a response to infection caused by
      non-tuberculous mycobacteria?
AB  - Two children, 4 and 8 years old, were skin tested with sensitins and found to
      have indurations of 20 mm. Sensitins are tuberculins deriving from non
      tuberculous mycobacteria. The children showed pathological enlargement of
      mediastinum on chest radiography. They were further examined, and no findings
      supported malignancy nor tuberculosis. The chest radiographs were normalizing
      within a few months. The large sensitin reactions together with the other
      findings indicate that the children had been infected with non-tuberculous
      mycobacteria.

PMID- 8740317
TI  - Truncated XPA protein detected in atypical group A xeroderma pigmentosum.
AB  - XPA protein from a patient with typical group A xeroderma pigmentosum (XP) and
      three atypical group-A XP patients were analysed. Immunoblot analysis of XPA
      proteins revealed that a typical group-A XP patient showed no XPA protein band,
      while a smaller, truncated XPA protein, which appears to be responsible for mid
      skin lesions and minimal neurological abnormalities, was detected in cells from
      three atypical group-A XP patients. Furthermore, the difference in the amount of
      truncated XPA protein correlated with the mildness of neurological manifestations
      in these three atypical group-A XP patients. The results suggest a correlation
      between clinical manifestations and qualitative and quantitative abnormalities of
      XPA protein products.

PMID- 8740318
TI  - Transient gastric outlet obstruction and tetralogy of Fallot: a true association
      or a coincidental finding?
AB  - Infants suffering from congenital heart anomalies who are receiving intravenous
      prostaglandins may present with gastric outlet obstruction. We describe a newborn
      with tetralogy of Fallot who was not being treated with prostaglandins and
      presented with gastric outlet obstruction. The typical clinical and radiological
      signs of infantile hypertrophic pyloric stenosis resolved spontaneously within
      several days. We suggest that there may be an association between cyanotic heart
      disease and gastric outlet obstruction unrelated to the use of prostaglandins.

PMID- 8740319
TI  - Type I diabetes mellitus, ketoacidosis and thromboembolism in an adolescent with
      Prader-Willi syndrome.

PMID- 8740320
TI  - Phenytoin protein binding and dosage requirements during acute and convalescent
      phases following brain injury.
AB  - OBJECTIVE: To longitudinally evaluate unbound and total serum phenytoin
      concentrations during intravenous phenytoin maintenance dosage and to determine
      the relationship among phenytoin protein binding, serum albumin, and unbound
      fatty acid concentrations in patients with head injuries during intensive care
      unit (ICU) and convalescent care. DESIGN: Serum albumin and phenytoin unbound
      fraction were determined twice weekly during ICU and convalescent care in 10
      patients receiving phenytoin following acute brain injury. Phenytoin protein
      binding was also determined in 10 healthy control subjects. MAIN OUTCOME
      MEASURES: Longitudinal serum phenytoin concentrations associated with dosage
      adjustments targeted to achieve unbound phenytoin serum concentrations between
      1.0 and 2.0 mg/L were documented during ICU and convalescent care. Longitudinal
      phenytoin binding was correlated with serum albumin and unbound fatty acid
      concentrations in neurotrauma patients. RESULTS: ICU patients received
      intravenous therapy for a mean of 15.0 days. The mean +/- SD initial phenytoin
      intravenous dosage regimen of 6.0 +/- 0.7 mg/kg/d resulted in mean +/- SD total
      and unbound phenytoin concentrations of 3.2 +/- 2.3 and 0.3 +/- 0.2 mg/L. Two
      patients had seizures associated with low phenytoin concentrations. Four patients
      continued to receive oral phenytoin therapy during convalescent care; phenytoin
      dosage requirements decreased over time in these patients. During acute and
      convalescent care, the phenytoin unbound fraction ranged from 6.0% to 18.3% and
      correlated with albumin (r2 = 0.61, p < 0.0001) but did not correlate with
      unbound fatty acid concentrations. The mean phenytoin unbound fraction was 10.1%
      and 8.9% for the ICU and convalescent patients with brain injuries, respectively,
      and was 7.0% for the healthy volunteers. CONCLUSIONS: Phenytoin protein binding
      was significantly correlated with albumin and was more variable in ICU and
      convalescent patients with brain injuries than in healthy volunteers. The high
      dosage requirements and subtherapeutic unbound phenytoin concentrations observed
      during acute care are best explained by increased metabolism. Phenytoin dosage
      requirements decreased during convalescence.

PMID- 8740321
TI  - Changing physician behavior in ordering digoxin assays.
AB  - OBJECTIVE: To assess the ability to modify physicians' use of serum digoxin
      assays in a sustained fashion through (1) an educational intervention by a
      clinical pharmacist, and (2) changes in the computerized medical information
      system. DESIGN: A before/after methodology was used to compare test use by
      hospital staff physicians in two phases. Phase 1 was an educational intervention
      conducted by a clinical pharmacist with an 8-month follow-up. Phase 2 was a
      medical information system intervention with a 12-month follow-up. PATIENTS:
      Adult inpatients from July 1990 through December 1993 who received either digoxin
      therapy or at least one serum digoxin assay. MAIN OUTCOME MEASURE: Digoxin assays
      per patient day while receiving digoxin (assays/digoxin day), in-hospital
      mortality, and length of stay were compared before and after implementation of
      the interventions. RESULTS: A total of 9468 patients received a digoxin and/or
      serum digoxin assay. Baseline use of serum digoxin assays was 0.178
      assays/digoxin day. Following phase 1, the educational intervention, use declined
      20.2% to 0.142 assays/digoxin day (p < 0.03). After phase 2, the implementation
      of changes in the medical information system, digoxin assay use was maintained at
      16.3% less than that at baseline (p < 0.03). Patient mortality was unaffected.
      CONCLUSIONS: A low-intensity educational intervention by a clinical pharmacist
      supplemented by medical information system modification resulted in an important
      decrease in the use of digoxin assays. The change in physician behavior was
      sustained for more than 18 months. The model presented is not labor intensive,
      does not require continuous maintenance by healthcare personnel for a sustained
      effect, and may be widely applicable to healthcare providers.

PMID- 8740322
TI  - The asthma year in Swedish pharmacies: a nationwide information and
      pharmaceutical care program for patients with asthma.
AB  - OBJECTIVE: To increase the understanding of asthma among patients and the general
      public in Sweden and to increase the collaboration among healthcare personnel for
      the benefit of asthma patients. DESIGN: Based on the results from problem
      detection studies, Apoteksbolaget, the national organization for pharmacies in
      Sweden, designed a program to educate healthcare professionals and the public
      about asthma. Entitled the "Asthma Year," all pharmacy staffs were offered
      education on asthma, patients were provided written information and audiovisual
      materials, and the general public was made more aware of asthma through local
      media. SETTING: Pharmacies, healthcare centers, hospital outpatient areas,
      libraries, places of work, and domestic airports. PARTICIPANTS: All pharmacy
      staffs (12,000 persons) were offered an education on asthma. Patients with asthma
      were offered brochures and leaflets in pharmacies and information in the pharmacy
      magazine Apoteket. The general public received information about asthma through
      posters, radio, and television. MAIN OUTCOME MEASURES: The evaluations of the
      Asthma Year indicate that the activities had an impact on the public, on patients
      with asthma, and on the pharmacy staffs. RESULTS: About 4.5 million people in
      Sweden (42% of the population) observed the Asthma Year or received information
      about asthma, and 49% of the patients learned something new about their disease.
      Twice as many patients used steroid therapy regularly after the campaign than
      before. Of the pharmacy staffs, 96% were favorable to the idea of working with
      campaign years and 85% believed that they were personally involved with the
      activities. CONCLUSIONS: Patient outcomes in terms of reduced morbidity have not
      been possible to document, but the number of deaths from asthma in Sweden
      decreased from 438 during the previous year to 398 during the Asthma Year.

PMID- 8740323
TI  - Combining event rates from clinical trials: comparison of Bayesian and classical
      methods.
AB  - OBJECTIVE: To compare an empirical Bayesian, a fully Bayesian, and a classical
      fixed-effect (Peto) method for pooling event rates from separate epidemiologic
      studies or clinical trials. DESIGN: Four data sets used in meta-analyses by
      previous authors were evaluated. The first data set concerned death rates
      observed in clinical trials of beta-blockers, the second to lung cancer and
      smoking in 14 case-control studies, the third to drowsiness induced by the
      antihistamine compound chlorpheniramine, and the fourth to the use of intravenous
      magnesium in patients with suspected myocardial infarction. Randomly chosen data
      points were made more extreme to test the methods further. MAIN OUTCOME MEASURES:
      Pooled estimates of effect expressed as odds ratios and their associated 95%
      confidence intervals. RESULTS: All three methods gave comparable results with
      respect to the 95% confidence interval, although the Bayesian methods gave
      generally wider interval estimates. However, the point estimates for the
      individual studies were substantially different, particularly for small studies.
      CONCLUSIONS: For the data sets considered, Bayesian methods, which are computer
      intensive but intuitively appealing, provided results that were consistent with
      the classic fixed-effect Peto method. Introduction of the more extreme data
      points did not alter this conclusion.

PMID- 8740324
TI  - Stability of human recombinant epoetin alfa in commonly used neonatal intravenous
      solutions.
AB  - OBJECTIVE: To measure epoetin alfa concentrations after adding it to a variety of
      commonly used neonatal intravenous fluids to determine the stability of epoetin
      alfa over time. DESIGN: Epoetin alfa was added to the following fluids: sterile
      water; NaCl 0.9%; dextrose 10% in water; dextrose 10% with albumin at
      concentrations of 0.01%, 0.05%, and 0.1%; and total parenteral nutrition solution
      containing either 0.5% or 2.25% amino acids. The fluid was administered through
      intravenous tubing, a T-connector, and catheter, and samples were collected at 0,
      2, 4, 8, and 24 hours. MAIN OUTCOME MEASURES: Epoetin alfa concentrations were
      compared with the measured original preinfusion concentration and recorded as the
      percentage recovered. RESULTS: Concentrations declined significantly in all
      fluids containing less than 0.05% protein, but remained stable over 24 hours in
      fluids containing 0.05% or more protein. CONCLUSIONS: We conclude that epoetin
      alfa should be mixed in intravenous fluids containing at least 0.05% protein.

PMID- 8740325
TI  - Effects of ofloxacin administration on the reliability of urine glucose testing.
AB  - OBJECTIVE: To study the effects of ofloxacin on the reliability of urine glucose
      testing. DESIGN: Open-label, nonrandomized. SETTING: A university-affiliated
      tertiary care hospital, ambulatory clinic. PARTICIPANTS: Ten healthy volunteers
      (8 men and 2 women) aged 22-39 years. MAIN OUTCOME MEASURES: Phase I (in vitro)
      involved the addition of selected amounts of ofloxacin to a set of standard 50-mL
      urine samples prepared to simulate glycosuria. Phase II (in vivo) involved the
      oral administration of ofloxacin 400 mg to 10 subjects. Urine was collected: (1)
      immediately predose, (2) pooled 0-4 hours postdose, and (3) pooled 4-8 hours
      postdose. Known glucose concentrations were then added to these samples.
      Clinitest and Diastix tests were performed on all samples. The accuracy of these
      tests in determining glucose concentrations was compared among urine samples
      taken before and after ofloxacin dosing. RESULTS: None of the ofloxacin
      concentrations in phase I (0, 25, 50, 100, 200, 400, and 800 micrograms/mL)
      influenced these testing methods at the urine glucose concentrations of 0.0%,
      0.5%, 1%, and 2%. Likewise, the accuracy of these two tests was unaffected by
      ofloxacin administration in phase II. CONCLUSIONS: In single-dose administration,
      ofloxacin does not interfere with Clinitest or Diastix for determining urine
      glucose concentrations.

PMID- 8740326
TI  - Pharmacokinetics and pharmacodynamics of glyburide in young and elderly patients
      with non-insulin-dependent diabetes mellitus.
AB  - OBJECTIVE: To determine the influence of age on the pharmacokinetics and
      pharmacodynamics of glyburide after acute and chronic dosing in young and elderly
      subjects with non-insulin-dependent diabetes mellitus. DESIGN: Ten elderly (mean
      age 69.3 +/- 3.1 y) and 10 younger (mean age 45.6 +/- 4.5 y) patients received a
      glucose challenge test at baseline, with a 2.5-mg dose of glyburide at week 0
      (acute dose) and again at weeks 6 and 12 of chronic glyburide therapy. Glyburide
      doses were titrated to a maximum daily dosage of 20 mg to achieve a glucose
      concentration of 7.8 mmol/L or less. During 24-h pharmacokinetic determinations
      at weeks 0, 6, and 12, serial blood samples were obtained for glyburide
      determination with HPLC. Serial blood samples for glucose, insulin, and C-peptide
      determinations were obtained at baseline (week -1) and at weeks 0, 6, and 12.
      RESULTS: All pharmacokinetic parameters assessed for glyburide were statistically
      comparable between the two age groups with the exception of a shorter time to
      peak concentration in the elderly at weeks 0 and 12. The glucose pharmacodynamic
      response to glyburide was not statistically different between the two groups.
      However, there was a statistically significant greater C-peptide response in the
      elderly group at all evaluation weeks. CONCLUSIONS: Aging appears to have no
      influence on the pharmacokinetics of glyburide. Observed pharmacodynamic
      differences indicate the necessity for dosage titration to a specified
      therapeutic response regardless of patient age.

PMID- 8740327
TI  - Enoxaparin for unstable angina and ancrod for cardiac surgery following heparin
      allergy.
AB  - OBJECTIVE: To describe a patient who presented with heparin allergy and required
      alternate anticoagulation for unstable angina and coronary artery bypass surgery.
      To review therapeutic alternatives to porcine heparin for patients with
      hypersensitivity or intolerance to standard heparin anticoagulation. CASE
      SUMMARY: A 74-year-old man with a 15-year-old coronary artery bypass graft
      presented to the emergency room with unstable angina and was scheduled for urgent
      coronary artery revascularization. A bolus dose of porcine heparin was
      administered followed by a continuous infusion. Shortly afterward the patient
      developed a type I allergic reaction to the porcine heparin that was confirmed by
      rechallenge. Three alternatives to porcine heparin were tried, including bovine
      lung heparin, low-molecular-weight heparin (enoxaparin), and ancrod. The patient
      was found to be cross-sensitive to bovine lung heparin, but tolerated enoxaparin
      for unstable angina without cross-sensitivity. Anticoagulation for
      cardiopulmonary bypass was achieved with an infusion of ancrod that was later
      reversed with cryoprecipitate. The patient was discharged postoperatively on day
      5 without the complication of excessive bleeding. DISCUSSION: Type I allergic
      reaction to unfractionated heparin is a rare occurrence and could be the result
      of a variety of factors. Possible causes for the reaction include a porcine
      protein, a preservative contained in the heparin solution, or a hapten formed
      between heparin and a plasma protein. We considered four alternatives to heparin
      anticoagulation: rush desensitization, bovine lung heparin, low-molecular-weight
      heparin, and ancrod. The patient was cross-sensitive to bovine lung heparin, but
      was able to tolerate low-molecular-weight heparin (enoxaparin). This was
      unexpected because enoxaparin is derived from unfractionated porcine heparin.
      Testing for cross-sensitivity had no value in this case, as two negative
      subcutaneous test doses were followed by dramatic reactions when the drugs were
      given intravenously. Although enoxaparin has been used for anticoagulation during
      bypass surgery, there is more experience with ancrod as an alternative to
      heparin. Repeat bypass surgery, which normally results in above-average blood
      loss, was successfully performed with a very low fibrinogen concentration (< 0.15
      g/L) during ancrod anticoagulation. CONCLUSIONS: We conclude that ancrod was a
      safe and effective alternative to heparin for coronary artery bypass surgery in
      this patient in whom a heparin product had caused a hypersensitivity reaction. We
      discovered on two occasions that a negative subcutaneous test dose for heparin
      allergy did not predict a severe type I allergic reaction when the heparin was
      later administered intravenously. Furthermore, we found that a low-molecular
      weight heparin administered subcutaneously for a short period of time did not
      cause cross-sensitivity in a patient with a type I allergy to unfractionated
      heparin.

PMID- 8740328
TI  - Serum-sickness-like reaction associated with minocycline therapy in adolescents.
AB  - OBJECTIVE: To describe a serum-sickness-like reaction in five adolescents treated
      with minocycline. CASE SUMMARY: Five adolescents developed a rash and
      arthralgias/arthritis after taking minocycline for 10-30 days. Symptoms resolved
      gradually after the medication was stopped. DISCUSSION: Serum sickness is not
      described in the pharmacology literature as an adverse effect of minocycline, and
      in the English literature there are only two case reports. The migration
      inhibitory factor assay and mast cell degranulation test were positive in four of
      the five patients. The results of these assays were consistent with a role for
      minocycline in causing these reactions. CONCLUSIONS: Clinicians should be aware
      of the possibility of serum-sickness-like reaction as an adverse effect of
      minocycline.

PMID- 8740329
TI  - Possible erythromelalgia-like syndrome associated with nifedipine in a patient
      with Raynaud's phenomenon.
AB  - OBJECTIVE: To describe a patient who was diagnosed with Raynaud's phenomenon, was
      prescribed immediate-release nifedipine, and developed a possible erythromelalgia
      like syndrome. CASE SUMMARY: A 24-year-old white woman with a history of
      esophageal spasms and Raynaud's phenomenon was prescribed nifedipine 10 mg po
      qid. Approximately 1 hour after the patient had taken the fourth dose of
      nifedipine, she experienced acute erythema and a burning sensation in her feet
      and lower limbs, light-headedness, and palpitations. Because of a reportedly
      abnormally low blood pressure, the patient took diphenhydramine 50 mg po and
      proceeded to the clinic. On arrival, abnormal vital signs were BP 140/48 mm Hg
      and HR 130 beats/min. Without any other medical intervention, approximately 30
      minutes later her blood pressure and heart rate had returned to baseline at
      122/60 mm Hg and 96 beats/min, respectively. The nifedipine was permanently
      discontinued and the patient's symptoms completely resolved over 24 hours.
      DISCUSSION: The characteristic symptoms of erythromelalgia include burning pain,
      increased skin temperature, and erythema of the extremities, usually to the feet,
      lower legs, and, less often, the hands. Erythromelalgia-like syndromes secondary
      to the administration of many medications have been reported. Several nifedipine
      related reports describe an erythromelalgia-like syndrome similar to our reported
      case. CONCLUSIONS: Because the patient was not taking any other medications and
      the symptoms started with the administration of nifedipine and were relieved
      after its discontinuation, nifedipine was thought to be the cause of the
      erythromelalgia-like syndrome.

PMID- 8740330
TI  - Quinine clearance in continuous venovenous hemofiltration.
AB  - OBJECTIVE: To describe a case involving the removal of quinine by continuous
      venovenous hemofiltration (CVVH) in a patient with malaria and acute renal
      failure and to present recommendations on the dosing of quinine in such patients.
      CASE SUMMARY: A 50-year-old white man developed Plasmodium falciparum malaria
      following a visit to Nigeria. Although he received intravenous quinine, his
      condition deteriorated and he required intensive care management, including CVVH
      for the management of his acute renal failure. Quinine plasma concentrations were
      measured to determine both total body and extracorporeal clearance of the drug.
      DISCUSSION: To our knowledge this is the first report quantifying the removal of
      quinine by CVVH. The drug is not significantly removed by this extracorporeal
      process. The filter clearance accounted for less than 1.5% of the total body
      clearance. CONCLUSIONS: Initially the dosage of quinine administered to patients
      presenting with P. falciparum infection should not be reduced because of renal
      failure. This is particularly important when cerebral involvement is suspected.
      Subsequent dosage modification should reflect the severity of the patient's
      clinical condition and the plasma quinine concentration achieved, and should not
      be limited by the degree of renal impairment present.

PMID- 8740331
TI  - The cholesterol controversy.
AB  - OBJECTIVE: To provide information about the controversy associated with lowering
      of cholesterol concentrations to prevent coronary heart disease (CHD). DATA
      SOURCES: Studies, review articles, and editorials identified from MEDLINE
      searches (from 1966 to 1995) and bibliographies of identified articles. STUDY
      SELECTION: Studies, review articles, and editorials addressing controversial
      issues related to cholesterol lowering. DATA EXTRACTION: Pertinent information
      was selected and the data synthesized into a review format. DATA SYNTHESIS:
      Hypercholesterolemia is a well-known CHD risk factor. Reduction of serum
      cholesterol concentrations has been shown to reduce the incidence of CHD.
      Unfortunately, cholesterol lowering also appears to increase the risk for cancer,
      accidental and violent death, stroke, and oddly enough, CHD when certain
      medications are used. CONCLUSIONS: Significant reductions in serum cholesterol
      concentrations can be achieved with cholesterol-lowering interventions. However,
      the benefits associated with cholesterol reduction may not outweigh the risks in
      all patients with hypercholesterolemia. Cholesterol-lowering interventions should
      be recommended with caution in patients at increased risk of cancer, stroke, and
      depression. Caution should also be used when recommending fibric acid derivatives
      for patients with existing CHD.

PMID- 8740332
TI  - Vinorelbine: a new antineoplastic drug for the treatment of non-small-cell lung
      cancer.
AB  - OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics, clinical
      activity, adverse effects, and dosage and administration guidelines for
      vinorelbine in the treatment of non-small-cell lung cancer (NSCLC). DATA SOURCES:
      A MEDLINE search (1989-1995) using the terms vinorelbine and Navelbine was
      conducted. Additional unpublished data were provided by Glaxo Wellcome Drug
      Information. STUDY SELECTION AND DATA EXTRACTION: The articles chosen for
      inclusion all appeared in peer-reviewed journals. Pertinent abstracts, as judged
      by the authors, were also included. DATA SYNTHESIS: Vinorelbine is a new
      semisynthetic vinca alkaloid approved by the Food and Drug Administration for the
      first-line treatment of patients with advanced NSCLC. The drug demonstrated a
      broad spectrum of antitumor activity in preclinical studies and produced dose
      limiting neutropenia in Phase I trials. In Phase II studies, an overall response
      rate of approximately 30% was reported with single-agent vinorelbine.
      Furthermore, in large, multicenter, randomized Phase III trials, treatment with
      vinorelbine alone and in combination with cisplatin resulted in improved survival
      compared with controls. The drug was well tolerated, with granulocytopenia being
      the most commonly reported adverse effect. However, the incidence of fever and
      hospitalization associated with this granulocytopenia was exceptionally low. The
      recommended dose is 30 mg/m2 weekly administered by intravenous injection or
      infusion. CONCLUSIONS: As no specific chemotherapy regimen has previously been
      regarded as standard therapy for advanced NSCLC, vinorelbine is a promising new
      treatment for this patient population. It has been shown in several randomized,
      controlled trials to increase survival without compromising quality of life.

PMID- 8740333
TI  - Acute management of cancer-related hypercalcemia.
AB  - OBJECTIVE: To review the pathogenesis and pharmacologic treatment of acute
      hypercalcemia associated with malignancy. DATA SOURCES: A MEDLINE search (1966 to
      1995) of the English-language literature pertaining to acute hypercalcemia was
      performed. Additional literature was obtained from reference lists of articles
      identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles
      discussing the etiology and medical management of cancer-related acute
      hypercalcemia were considered in this review. Clinical trials reporting efficacy
      and safety of antihypercalcemic agents were also included. Information selected
      in the review was based on the discretion of the authors. DATA SYNTHESIS:
      Hypercalcemia is a life-threatening disorder associated with malignancy. It
      occurs in approximately 10-20% of patients with cancer. A variety of medications
      have been used in the management of hypercalcemia including bisphosphonates,
      calcitonin, furosemide, gallium nitrate, glucocorticoids, NaCl 0.9%, and
      plicamycin. Each of these agents has been reviewed with consideration of
      pharmacologic mechanism of action, evaluation of clinical trials, recommended
      dosages, efficacy, safety, cost, and role in treating cancer-related acute
      hypercalcemia. CONCLUSIONS: Immediate management of cancer-related acute
      hypercalcemia to prevent death and provide symptomatic relief is warranted.
      Severity determined by symptoms, calcium concentrations, and the overall status
      of the patient are important considerations in selecting appropriate therapy.
      Although the specific role of individual agents may vary, hydration remains the
      cornerstone of therapy. NaCl 0.9%, calcitonin, and pamidronate disodium have
      established roles as dominant first-line agents for the management of acute
      hypercalcemia associated with malignancy.

PMID- 8740334
TI  - Acetazolamide in the treatment of seizures.
AB  - OBJECTIVE: To summarize the pharmacology, pharmacokinetics, efficacy, and safety
      of acetazolamide and to evaluate its therapeutic role in patients with epilepsy.
      DATA SOURCES: A computerized search of the MEDLINE (OVID) database (1966-1994)
      was used to identify publications regarding acetazolamide. The MEDLINE search was
      supplemented by information from textbooks. STUDY SELECTION: Included were
      English-language review articles, clinical trials, cohort studies, and case
      reports. Topics investigated included basic pharmacology, therapeutics,
      toxicology, adverse reactions, dosage, administration, and pharmacokinetics of
      acetazolamide. DATA SYNTHESIS: Acetazolamide, a carbonic anhydrase inhibitor, has
      been approved for the treatment of epilepsy since 1953. Acetazolamide is
      primarily used in combination therapy with other antiepileptic medications in
      both children and adults although it may be used as monotherapy. Drug
      concentration monitoring has not been found to be routinely beneficial. Adverse
      effects include kidney stones, metabolic acidosis, lethargy, appetite
      suppression, paresthesias, and rare blood dyscrasias. Partial tolerance may
      develop to the antiepileptic activity. CONCLUSIONS: Acetazolamide is a beneficial
      adjunctive agent in the pharmacotherapy of epilepsy and should be considered in
      refractory epilepsy. Although it may be useful in partial, myoclonic, absence,
      and primary generalized tonic-clonic seizures uncontrolled by other marketed
      agents, acetazolamide has been inadequately studied by current standards and its
      use has been limited.

PMID- 8740335
TI  - Possible interaction involving phenytoin, dexamethasone, and antineoplastic
      agents: a case report and review.
AB  - OBJECTIVE: To describe a patient with subtherapeutic phenytoin concentrations and
      to review the literature regarding a possible interaction between phenytoin and
      chemotherapeutic agents as well as dexamethasone. CASE SUMMARY: A 29-year-old
      white man with brain metastases secondary to malignant melanoma consistently had
      suboptimal phenytoin concentrations while receiving chemotherapy consisting of
      cisplatin, carmustine, dacarbazine, and tamoxifen. In addition, this patient
      received dexamethasone, which may have influenced his phenytoin concentrations.
      DATA SOURCES AND STUDY SELECTION: Case reports were identified through a MEDLINE
      search and by cross referencing the articles identified. DISCUSSION: The
      available literature addressing suboptimal phenytoin concentrations in the
      setting of chemotherapy is reviewed. Aggressive dosing of phenytoin may be
      required to achieve therapeutic concentrations in patients who are concurrently
      receiving chemotherapy and/or dexamethasone, especially in patients who fall
      outside the predictive pharmacokinetic model for phenytoin. CONCLUSIONS:
      Subtherapeutic phenytoin concentrations may be decreased secondary to several
      proposed mechanisms: (1) the patient falls outside the predicted pharmacokinetic
      population parameters for phenytoin, (2) phenytoin absorption is decreased
      secondary to chemotherapy-induced gastrointestinal toxicity, and (3) metabolism
      of phenytoin is increased secondary to chemotherapy agents.

PMID- 8740336
TI  - Pathophysiology and management of the serotonin syndrome.
AB  - OBJECTIVE: To review the symptoms, pathophysiology, and treatment of the
      serotonin syndrome (SS). DATA SOURCES: A MEDLINE search (1957-1995) of the
      English-language literature pertaining to the SS was performed. Additional
      literature was obtained from reference lists of pertinent articles identified
      through the search. STUDY SELECTION AND DATA EXTRACTION: All articles were
      considered for possible inclusion in the review. Pertinent information, as judged
      by the authors, was selected for discussion. DATA SYNTHESIS: The SS, an
      occasionally fatal disorder, is characterized by symptoms such as mental status
      changes, seizures, myoclonus, and blood dyscrasias. Both the central and
      peripheral serotonergic systems and several serotonin receptor types are involved
      in the symptomatology of the SS. The pathogenesis of SS may be due to endogenous
      as well as iatrogenic deficits in peripheral serotonin metabolism, a stimulus for
      release of serotonin, and interactions with other neurotransmitter systems.
      Lorazepam, serotonin-blockers, and nitroglycerin have been used successfully to
      treat SS. CONCLUSIONS: The SS is increasingly recognized and reported in the
      literature. Clinical and basic science research have increased our understanding
      of the pathophysiology, conditions, and agents that may predispose to the
      development of the syndrome. Newer treatment strategies are discussed.

PMID- 8740337
TI  - Nystatin prophylaxis in immunocompromised children.
AB  - In conclusion, the use of nystatin for fungal prophylaxis in
      hematology/oncology/bone marrow transplantation patients appears to convey little
      or no benefit over no therapy. Nystatin treatment significantly reduced the
      frequency of multiple-site colonization and of persistently positive
      oropharyngeal cultures, but was not able to prevent the occurrence of
      disseminated fungal infections. Other antifungal agents (e.g., ketoconazole,
      fluconazole, itraconazole, oral or intravenous amphotericin B) may be of benefit.
      Studies comparing nystatin with other agents are available in the literature but
      are beyond the scope of this review.

PMID- 8740338
TI  - Lodoxamide in vernal keratoconjunctivitis.
AB  - Lodoxamide may be superior compared with cromolyn sodium for treatment of VKC. It
      is difficult, however, to conclusively determine the superiority of lodoxamide
      compared with cromolyn from the three studies reviewed in this article.
      Optimally, a triple-blind, randomized, placebo-controlled, multicenter trial
      involving the ophthalmic products cromolyn sodium 4%, lodoxamide 0.1%, and
      placebo (preferably NaCl 0.9%) with a treatment duration of at least 90 days and
      a similar sample size for each study group would lend the most credence to the
      determination of superiority of lodoxamide compared with cromolyn sodium for the
      treatment of VKC.

PMID- 8740339
TI  - Cholesterol-lowering therapy: is there really a controversy?
AB  - Geurian concludes that recommendations for the management of hypercholesterolemia
      are difficult to make because a previously black and white issue is becoming
      "increasingly gray." Actually, it appears that the opposite is occurring. Our
      knowledge of atherogenesis, as well as the mechanisms by which thromboembolic
      events occur, continues to expand. We are gaining new insights into the
      mechanisms by which cholesterol-lowering therapy can prevent the development of
      coronary events. Newer cholesterol-lowering agents are more potent than those
      previously available and make substantial reductions more readily achievable.
      Finally, we are gaining a better understanding of the relative benefits of
      cholesterol-lowering therapy in various patient populations, although more work
      is needed, particularly in women and older patients. Cholesterol-lowering therapy
      has had an important positive impact on CHD, particularly in preventing recurrent
      events and reducing mortality when used as secondary prevention. Clearly, there
      are substantial numbers of patients who will benefit greatly from cholesterol
      lowering drugs, and clinicans should not be dissuaded from providing this
      valuable form of drug therapy.

PMID- 8740340
TI  - Tacrolimus-phenytoin interaction.

PMID- 8740341
TI  - Changes in interleukin-6 concentrations following epilepsy surgery: potential
      influence on carbamazepine pharmacokinetics.

PMID- 8740342
TI  - Pseudopheochromocytoma in a patient with Parkinson's disease.

PMID- 8740343
TI  - Aplastic anemia with ticlopidine therapy in two Chinese patients.

PMID- 8740344
TI  - Carbamazepine-lithium drug interaction.

PMID- 8740345
TI  - Tetracycline-induced oral mucosal ulcerations.

PMID- 8740346
TI  - Comment: clindamycin meta-analysis.

PMID- 8740347
TI  - Comment: haloperidol and diphenhydramine compatibility.

PMID- 8740349
TI  - Vaccination coverage levels among children aged 19-35 months--US, April 1994
      March 1995.

PMID- 8740348
TI  - Mortality attributable to HIV infection among persons aged 25-44 years--US, 1994.

PMID- 8740350
TI  - Mechanical circulatory support: lessons from a single centre.
AB  - Over recent years, a number of different mechanical circulatory support (MCS)
      products have been developed to a stage where they are no longer investigational
      devices. Registry data provide some information, but this is limited by the mix
      of historical and contemporary data and the voluntary nature of the
      contributions. As yet, there are no clear guidelines for patient selection, the
      differential application of generically different devices or for optimal patient
      management. Ours is a busy centre offering a comprehensive cardiovascular
      service. This review details our experience since 1987 and 189 patients supported
      with five different types of device, used in all of the common applications. Our
      experience has permitted the formulation of some general principles and
      guidelines. Data published by registries and by individual manufacturers are, as
      yet, not standardized. We hope that our experience will be of interest to those
      centres wishing to establish a mechanical assist service.

PMID- 8740351
TI  - The acute phase response to cardiopulmonary bypass in children.
AB  - The endocrine phase of the stress response to cardiopulmonary bypass in children
      is known to be subtly different from that seen in adults. The aim of this
      investigation was to determine whether there are similar differences in the acute
      phase response. Thirteen children were studied (mean age 2.65 years). Each child
      had congenital heart disease and underwent corrective cardiac surgery. Blood
      samples taken two days prior to operation and at 6, 9, 12, 24, 48 and 120 hours
      after were analysed for C-reactive protein, albumin, caeruloplasmin, zinc and
      copper concentrations. Metal:carrier protein molar ratios were also calculated.
      Results demonstrate changes which, although similar to those seen in adults,
      differed both quantitatively and qualitatively. This is explained by the concept
      of immaturity leading to a generally poor capacity for protein synthesis and a
      relative inability to respond to altered circumstances.

PMID- 8740352
TI  - Differences in blood activation related to roller/centrifugal pumps and heparin
      coated/uncoated surfaces in a cardiopulmonary bypass model circuit.
AB  - An in vitro model cardiopulmonary bypass (CPB) circuit consisting ot tubing,
      oxygenator and venous reservoirs with either a roller or a centrifugal pump, and
      with either heparin-coated (Carmeda Bioactive Surface, CBAS) or uncoated
      surfaces, was studied with respect to 'blood activation', using small-scale-based
      blood volume (450 + 500 ml). Sixteen circuits were tested in each pump group,
      eight with and eight without heparin-coated surfaces, by circulating heparinized
      fresh human blood for 72 hours at 30 degrees C. Blood plasma, sampled at defined
      intervals, was analysed for haemolysis (lactate dehydrogenase and potassium),
      complement activation (C3bc and C5b-9 (TCC)), complement lytic inhibitors
      (vitronectin and clusterin), coagulation activation (fibrinopeptide A),
      granulocyte (lactoferrin and myeloperoxidase) and platelet (beta-thromboglobulin)
      activation and contaminating endotoxin. The heparin coating significantly reduced
      the concentrations of C3bc, TCC, fibrinopeptide A, lactoferrin, myeloperoxidase
      and beta-thromboglobulin. The two pump types did not differ with respect to these
      parameters, but the roller pump caused significantly higher increases in plasma
      LDH and potassium and significantly greater reductions in clusterin and
      vitronectin than the centrifugal pump. Endotoxin concentration was low at the
      start and after 24 hours in all groups. These results confirm that heparin-coated
      CPB surfaces reduce blood activation, and suggest that centrifugal pumps cause
      less haemolysis and less reduction in lytic complement inhibitors than roller
      pumps.

PMID- 8740353
TI  - The activated clotting time loading dose response ratio (ACTLORR) as an indicator
      of heparin demand during cardiopulmonary bypass.
AB  - Data relating to the activated clotting time response to a 4 mg/kg heparin
      loading dose were collected prospectively in 358 patients having cardiopulmonary
      bypass. After excluding patients with factors known to cause relative heparin
      resistance or sensitivity, the activated clotting time (ACT) loading dose
      response ratio (ACTLORR) was calculated retrospectively in 263 patients and found
      to correlate significantly (p = 0.0001) with the need for extra heparin
      administration during bypass. Where the ACTLORR was above 5.5, 92% of patients
      required no additional heparin during the first 90 minutes of bypass (n = 98).
      Where the ACTLORR was between 4.0 and 5.0, it was far less predictive, with
      approximately 35% of patients requiring additional heparin. This study indicates
      that a large ACT response to the initial heparin loading dose (a high ACTLORR) is
      predictive of stable, adequate anticoagulation during the first 90 minutes of
      bypass, but that a low initial response is not necessarily associated with
      declining ACTs and the need for additional heparin administration.

PMID- 8740354
TI  - Factors influencing haemostasis and blood transfusion in cardiac surgery.
AB  - To find out the risk factors influencing perioperative bleeding and use of blood
      products in cardiac surgery so that appropriate interventions can be selected for
      blood conservation, risk factors were analysed in 343 cardiac surgical patients,
      retrospectively, by multiple regression technique. The results showed that the
      factors related to postoperative bleeding were male gender, Higgins score,
      cardiopulmonary bypass (CPB) time, operation procedures, intraoperative blood
      loss and use of internal mammary artery (IMA) graft. Factors related to
      perioperative homologous blood transfusions were emergency surgery, preoperative
      haemoglobin level, Higgins score, intraoperative blood loss, operation time and
      operation procedures. The geometric mean of postoperative bleeding in the entire
      series was 1085 ml and the mean packed red cell, plasma and platelet transfusions
      were 3.29 +/- 0.4, 1.96 +/- 0.39 and 0.21 +/- 0.05 units respectively. The
      incidence of homologous blood transfusion during the hospital stay was 58.9% for
      the entire series and 54.5% in the nonrevision patients. Emergency patients
      received significantly more blood transfusion (p = 0.0001). Perioperative blood
      loss and transfusions are still problems in cardiac surgery and certain patient
      groups in this study were identified as high risk; available blood conservation
      techniques, therefore, are recommended in these patients.

PMID- 8740355
TI  - Emboli generation by the Medtronic Maxima hard-shell adult venous reservoir in
      cardiopulmonary bypass circuits: a preliminary report.
AB  - Increases in right common carotid artery Doppler ultrasound signals typical of
      emboli were found in cardiopulmonary bypass patients when the Medtronic Maxima
      hard-shell adult combined venous and cardiotomy reservoir was operated at
      reservoir blood volumes near the manufacturer;s recommended minimum of 300 ml.
      The signals were reduced by increasing the reservoir blood volume. Possible
      microembolus generation in the top- and bottom-entry versions of this reservoir
      was investigated using an in vitro circuit and a colour flow Doppler monitor that
      was interfaced with a microprocessor to count the signals. The reservoir blood
      volume was progressively lowered in 100 ml increments below 1000 ml, and signals
      were counted over five minutes at each new level. Signal counts downstream of the
      reservoir increased exponentially after the volume was decreased below 1000 ml in
      the bottom-entry version, and 700 ml in the top-entry version. Ultrasonic
      monitoring, both upstream and downstream of the reservoir, showed that the source
      of these signals was the reservoir itself, and that recirculation of emboli
      around the circuit accounted for only a small proportion of the measured
      increase. Changes in circuit blood prime haematocrit within the range 0.11-0.31
      did not alter the signal counts. However, counts were profoundly affected by
      exposure of the circuit to nitrous oxide via a membrane oxygenator; this showed
      that the emboli were bubbles. Bubble formation may occur where venous blood
      enters the reservoir as this results in a fountaining effect when the reservoir
      volume is low. This effect appears to have been serendipitously reduced, but not
      eliminated, in the design of the top-entry version. It is recommended that
      perfusionists should not operate these reservoirs at volumes below 1000 and 700
      ml in the bottom- and top-entry versions respectively.

PMID- 8740356
TI  - Massive arterial air embolism during cardiopulmonary bypass: antegrade blood
      cardioplegia delivered by the pump--an accident waiting to happen.
AB  - Of the many possible causes of air embolism occurring in patients undergoing
      cardiopulmonary bypass (CPB), human error due to the perfusionist or the surgeon
      accounts for the vast majority. This case, however, presents a previously
      unreported, but recognized, cause of air embolism, due to a technical problem
      encountered during the administration of blood cardioplegia. The nature of some
      of the older CPB pumps allows the administration of cardioplegia at a time when
      the main CPB pump is not rotating. A situation may then arise whereby air may be
      entrained and delivered to the patient. The management of massive air embolism is
      discussed, and recommendations are made to prevent such an occurrence happening
      in the future.

PMID- 8740357
TI  - Deciphering the alphabet of G proteins: the structure of the alpha, beta, gamma
      heterotrimer.
AB  - The recent independent structure elucidations of two heterotrimeric G proteins
      represent a milestone in our understanding of the regulation of this important
      class of signal switch molecules. The results show how the introduction of GTP
      into the heterotrimer produces two signalling molecules: the G alpha-GTP and G
      beta, gamma subunits.

PMID- 8740358
TI  - Knowledge-based potentials for protein folding: what can we learn from known
      protein structures?
AB  - Empirical potentials capture the essence of regularities seen in protein
      structures and can be used in simulations and predictions of protein structure or
      function. Derivations of such potentials require comparisons to be made between
      experimentally derived protein structures and theoretically constructed reference
      states.

PMID- 8740359
TI  - Defining the structure and stability of macromolecular assemblies in solution:
      the re-emergence of analytical ultracentrifugation as a practical tool.

PMID- 8740360
TI  - X-ray structure of a hydroxamate inhibitor complex of stromelysin catalytic
      domain and its comparison with members of the zinc metalloproteinase superfamily.
AB  - BACKGROUND: Stromelysin belongs to a family of zinc-dependent endopeptidases
      referred to as matrix metalloproteinases (MMPs, matrixins) because of their
      capacity for selective degradation of various components of the extracellular
      matrix. Matrixins play key roles in diseases as diverse as arthritis and cancer
      and hence are important targets for therapeutic intervention. RESULTS: The
      crystal structure of the stromelysin catalytic domain (SCD) with bound
      hydroxamate inhibitor, solved by multiple isomorphous replacement, shows deep S1'
      specificity pocket which explains differences in inhibitors binding between the
      collagenases and stromelysin. The binding of calcium ions by loops at the two
      ends of a beta-strand which marks the boundary of the active site provides a
      structural rationale for the importance of these cations for stability and
      catalytic activity. Major differences between the matrixins are clustered in two
      regions forming the entrance to the active site and hence may be determinants of
      substrate selectivity. CONCLUSIONS: Structural comparisons of SCD with
      representative members of the metalloproteinase superfamily clearly highlight the
      conservation of key secondary structural elements, in spite of major variations
      in the sequences including insertions and deletions of functional domains.
      However, the three-dimensional structure of SCD, which is generally closely
      related to the collagenases, shows significant differences not only in the
      peripheral regions but also in the specificity pockets; these latter differences
      should facilitate the rational design of specific inhibitors.

PMID- 8740361
TI  - Difference imaging reveals ordered regions of RNA in turnip yellow mosaic virus.
AB  - BACKGROUND: Turnip yellow mosaic virus (TYMV) is a small icosahedral plant virus
      with a capsid containing 180 subunits arranged with hexamer-pentamer clustering.
      Cross-linking studies have indicated extensive contacts between RNA and coat
      protein, suggesting that substantial parts of the RNA might be icosahedrally
      ordered. RESULTS: Comparison of maps computed to a Fourier cut-off of 1.5 nm from
      electron micrographs of ice-embedded specimens of TYMV and of empty capsids
      produced by freeze-thawing reveals strong inner features around the threefold
      axes in the virus but not in the empty capsid. Internal features of subunit
      packing indicate that interhexamer contacts are closer than those between
      pentamers and hexamers and that pentamer density in the empty capsid is reduced
      relative to that in the virus. CONCLUSIONS: The differences between virus and
      empty capsid indicate that substantial parts of the RNA are icosahedrally ordered
      and that the exit of RNA on freeze-thawing is accompanied by the loss of at least
      one pentamer unit.

PMID- 8740362
TI  - Crystal structure of a dimeric octaheme cytochrome c3 (M(r) 26,000) from
      Desulfovibrio desulfuricans Norway.
AB  - BACKGROUND: The octaheme cytochrome C3 (M(r) 26,000; cc3) from Desulfovibrio
      desulfuricans Norway is a dimeric cytochrome made up of two identical subunits,
      each containing four heme groups. It is involved in the redox transfer chain of
      sulfate-reducing bacteria, which links the periplasmic oxidation of hydrogen to
      the cytoplasmic reduction of sulfate. The amino-acid sequence of cc3 shows
      similarities to that of the tetraheme cytochrome c3 (M(r) 13,000; c3) from the
      same bacteria. Structural analysis of cc3 forms a basis for understanding the
      precise roles of the multiheme-containing redox proteins and the reason for the
      presence of several different multiheme cytochromes in one bacterial strain.
      RESULTS: The crystal structure of cytochrome cc3 has been determined at 2.16 A
      resolution. The subunits display the c3 structural fold with significant amino
      acid substitutions, relative to the tetraheme cytochromes c3, in the regions of
      the dimer interface. The identical subunits are related by a crystallographic
      twofold axis, with one heme of each subunit in close contact. The overall
      structure and the environments of the different heme groups are compared with
      those of the tetraheme cytochromes c3. CONCLUSIONS: A common scheme for
      interactions between these types of cytochrome and their redox partners involves
      the interaction of a heme crevice, surrounded by positively charged lysine
      residues, with acidic residues surrounding the redox partner's functional group.
      Despite the relatively acidic character of cytochrome cc3, the crevice of one
      heme is surrounded by a high number of positively charged residues, in the same
      manner as has been reported for cytochromes c3. The environment of this heme is
      formed by four flexible surface loops which are variable in length and
      orientation in the different c3-type cytochromes although the overall structural
      folds are very similar. It has been proposed that this region, adapted in
      topology and charge, is the interaction site for physiological partners and is
      also most likely to be the interaction site in the dimeric cytochrome cc3.

PMID- 8740363
TI  - Structure of rat procathepsin B: model for inhibition of cysteine protease
      activity by the proregion.
AB  - BACKGROUND: Cysteine proteases of the papain superfamily are synthesized as
      inactive precursors with a 60-110 residue N-terminal prosegment. The propeptides
      are potent inhibitors of their parent proteases. Although the proregion binding
      mode has been elucidated for all other protease classes, that of the cysteine
      proteases remained elusive. RESULTS: We report the three-dimensional structure of
      rat procathepsin B, determined at 2.8 A resolution. The 62-residue proregion does
      not form a globular structure on its own, but folds along the surface of mature
      cathepsin B. The N-terminal part of the proregion packs against a surface loop,
      with Trp24p (p indicating the proregion) playing a pivotal role in these
      interactions. Inhibition occurs by blocking access to the active site: part of
      the proregion enters the substrate-binding cleft in a similar manner to a natural
      substrate, but in a reverse orientation. CONCLUSIONS: The structure of
      procathepsin B provides the first insight into the mode of interaction between a
      mature cysteine protease from the papain superfamily and its prosegment.
      Maturation results in only one loop of cathepsin B changing conformation
      significantly, replacing contacts lost by removal of the prosegment. Contrary to
      many other proproteases, no rearrangement of the N terminus occurs following
      activation. Binding of the prosegment involves interaction with regions of the
      enzyme remote from the substrate-binding cleft and suggests a novel strategy for
      inhibitor design. The region of the prosegment where the activating cleavage
      occurs makes little contact with the enzyme, leading to speculation on the
      activation mechanism.

PMID- 8740364
TI  - The 1.1 A crystal structure of the neuronal acetylcholine receptor antagonist,
      alpha-conotoxin PnIA from Conus pennaceus.
AB  - BACKGROUND: alpha-Conotoxins are peptide toxins, isolated from Conus snails, that
      block the nicotinic acetylcholine receptor (nAChR). The 16-residue peptides PnIA
      and PnIB from Conus pennaceus incorporate the same disulfide framework as other
      alpha-conotoxins but differ in function from most alpha-conotoxins by blocking
      the neuronal nAChR, rather than the skeletal muscle subtype. The crystal
      structure determination of PnIA was undertaken to identify structural and surface
      features that might be important for biological activity. RESULTS: The 1.1 A
      crystal structure of synthetic PnIA was determined by direct methods using the
      Shake-and-Bake program. The three-dimensional structure incorporates a beta turn
      followed by two alpha-helical turns. The conformation is stabilised by two
      disulfide bridges that form the interior of the molecule, with all other side
      chains oriented outwards. CONCLUSIONS: The compact architecture of the PnIA toxin
      provides a rigid framework for presentation of chemical groups that are required
      for activity. The structure is characterized by distinct hydrophobic and polar
      surfaces; a 16 A separation of the sole positive and negative charges (these two
      charged residues being located at opposite ends of the molecule); a hydrophobic
      region and a protruding tyrosine side chain. These features may be important for
      the specific interaction of PnIA with neuronal nAChR.

PMID- 8740365
TI  - Solution structure of an antiparallel purine motif triplex containing a T.CG
      pyrimidine base triple.
AB  - BACKGROUND: Triplex formation is an approach of potential use in regulating and
      mapping of gene sequences. However, such applications have been limited to
      homogeneous sequences consisting of stretches of purines or pyrimidines.
      Understanding how heterogeneous duplexes are recognized by a third strand
      oligonucleotide at the atomic resolution level is an essential step toward
      broadening the application of triplex formation into biochemical and biomedical
      areas. RESULTS: The solution structure of an antiparallel triplex (RRY6)
      containing a site of inversion (i.e. a T within a homopurine stretch, forming a
      T.CG base triple) has been determined using NMR-restrained computations in the
      presence of explicit water. The results reveal that within the RRY6 triplex the
      conformation of the duplex is mostly B-like and that of the third strand exhibits
      significant variations in interbase separations and backbone torsion angles. A
      major displacement of the inversion site T sugar in a 5'-direction, accompanied
      by the tilt of the T base in T.CG, was observed. The T.CG base triple contains a
      single hydrogen bond between T O4 and the exposed C amino proton and is
      stabilized by a number of interstrand and sequential van der Waal contacts. The
      structural comparisons of RRY6 with two related triplexes indicate localized
      perturbation at the non-classical base triple site. Various triplexes contain
      sugars in the C2'-endo family and the global features of their duplexes are
      similar. CONCLUSIONS: This study provides valuable information concerning the
      molecular basis of the specific recognition of a Watson-Crick base paired C
      residue at the inversion sites in the antiparallel triplex and should lead to
      general rules for designing triplexes containing heterogeneous sequences.

PMID- 8740366
TI  - Insights into substrate binding by D-2-ketoacid dehydrogenases from the structure
      of Lactobacillus pentosus D-lactate dehydrogenase.
AB  - BACKGROUND: D-Lactate dehydrogenases (D-LDHs) and L-lactate dehydrogenases (L
      LDHs) catalyze a reaction differing only in the chirality of the product. Both
      enzymes utilize the same kind of amino acid side chains in substrate binding and
      catalysis. Models based on D-LDH-related enzymes propose that these side chains
      assume identical roles in both enzymes with their active sites related by a
      simple geometrical relationship such as a mirror plane. RESULTS: The crystal
      structure of the homodimeric D-LDH from Lactobacillus pentosus has been
      determined to 2.6 A resolution by multiple isomorphous replacement methods and
      the resulting molecular model refined to an R-factor of 19.1%. Topologically, the
      enzyme is closely related to other D-2-ketoacid dehydrogenase enzymes. Each
      subunit comprises two domains enclosing a deep cleft containing the active site.
      Substrate binding and domain closure have been modelled. CONCLUSIONS: Comparison
      of the D-LDH structure with other members of the protein family and with the L
      specific enzyme has confirmed that no overall structural relationship exists
      between the L-LDH and D-LDH enzymes - they belong to distinct protein classes.
      The small size of the ketoacid substrate and the very restricted number of
      functionally appropriate side chains will constrain the choice of amino acids and
      their placement in the active site. Our models imply that although the same kinds
      of amino acids are involved in substrate binding their exact chemical role might
      differ in the two dehydrogenases.

PMID- 8740367
TI  - Pigment-pigment interactions and energy transfer in the antenna complex of the
      photosynthetic bacterium Rhodopseudomonas acidophila.
AB  - BACKGROUND: Photosynthesis starts with the absorption of solar radiation by
      antenna pigment molecules. In purple bacteria these chromophores,
      (bacteriochlorophyll a and carotenoid) are embedded in the membrane; they are non
      covalently bound to apoproteins which have the ability to modulate the
      chromophores' absorbing characteristics. The first structure of the bacterial
      antenna complex from Rhodopseudomonas acidophila, strain 10050, shows a ring of
      nonameric symmetry. Two concentric cylinders of apoproteins enclose the pigment
      molecules. The current resolution of the structure, to 2.5 A, allows us to begin
      to explore the mechanism of energy transfer among these pigments. RESULTS: The
      mechanism of energy transfer, from the short- to long-wavelength-absorbing
      pigments, is largely determined by the relative distances and orientations of the
      chromophores. In this paper we provide evidence that energy transfer between the
      B800 and B850 bacteriochlorophylls is largely via Forster induced dipole-dipole
      resonance. Strong Coulombic (exciton) coupling among the 18 short distanced
      chromophores in the B850 macrocycle is promoted by good alignment of the Qy
      dipoles. Singlet-singlet energy transfer from carotenoid to the B800 macrocycle
      appears to be minimal, with most of the energy transfer going to B850. The higher
      energy state of both chromophores dominates in more complex situations.
      CONCLUSIONS: The structure of the antenna complex not only shows Nature at its
      most aesthetic but also illustrates how clever and efficient the energy transfer
      mechanism has become, with singlet-singlet excitation being passed smoothly down
      the spectral gradient to the reaction centre.

PMID- 8740368
TI  - The evolution of an allosteric site in phosphorylase.
AB  - BACKGROUND: Glycogen phosphorylases consist of a conserved catalytic core onto
      which different regulatory sites are added. By comparing the structures of
      isozymes, we hope to understand the structural principles of allosteric
      regulation in this family of enzymes. Here, we focus on the differences in the
      glucose 6-phosphate (Glc-6-P) binding sites of two isozymes. RESULTS: We have
      refined the structure of Glc-6-P inhibited yeast phosphorylase b to 2.6 A and
      compared it with known structures of muscle phosphorylase. Glc-6-P binds in a
      novel way, interacting with a distinct set of secondary elements. Structural
      links connecting the Glc-6-P binding sites and catalytic sites are conserved,
      although the specific contacts are not. CONCLUSIONS: Our comparison reveals that
      the Glc-6-P binding site was modified over the course of evolution from yeast to
      vertebrates to become a bi-functional switch. The additional ability of muscle
      phosphorylase to be activated by AMP required the recruitment of structural
      elements into the binding site and sequence changes to create a binding subsite
      for adenine, whilst maintaining links to the catalytic site.

PMID- 8740369
TI  - Electrostatic control of GTP and GDP binding in the oncoprotein p21ras.
AB  - BACKGROUND: p21ras is one of the GTP-binding proteins that act as intercellular
      molecular switches. The GTP-bound form of p21ras sends a growth-promoting signal
      that is terminated once the protein is cycled back into its GDP-bound form. The
      interaction of guanine-nucleotide-exchange factors (GEFs) with p21ras leads to
      activation of the protein by promoting GDP --> GTP exchange. Oncogenic mutations
      of p21ras trap the protein in its biological active GTP-bound form. Other
      mutations interfere with the activity of GEF. Thus, it is important to explore
      the structural basis for the action of different mutations. RESULTS: The crystal
      structures of p21ras are correlated with the binding affinities of GTP and GDP by
      calculating the relevant electrostatic energies. It is demonstrated that such
      calculations can provide a road map to the location of 'hot' residues whose
      mutations are likely to change functional properties of the protein. Furthermore,
      calculations of the effect of specific mutations on GTP and GDP binding are
      consistent with those observed. This helps to analyze and locate functionally
      important parts of the protein. CONCLUSIONS: Our calculations indicate that the
      protein main chain provides a major contribution to the binding energies of
      nucleotides and probably plays a key role in relaying the effect of GEF action.
      Analysis of p21ras mutations in residues that are important for the proper
      function of GEFs suggests that the region comprising residues 62-67 in p21ras is
      the major GEF-binding site. This analysis and our computer simulations indicate
      that the effect of GEF is probably propagated to the P-loop (residues 10-17)
      through interaction between Gly60 and Gly12. This then reduces the interaction
      between the main-chain dipoles of the P-loop and the nucleotide. Finally, the
      results also suggest a possible relationship between the GTP --> GDP structural
      transition and the catalytic effect of the GTPase-activating protein.

PMID- 8740370
TI  - Mutations, molecules, and myotonia.

PMID- 8740371
TI  - Inactivation defects caused by myotonia-associated mutations in the sodium
      channel III-IV linker.
AB  - Missense mutations in the skeletal muscle Na+ channel alpha subunit occur in
      several heritable forms of myotonia and periodic paralysis. Distinct phenotypes
      arise from mutations at two sites within the III-IV cytoplasmic loop: myotonia
      without weakness due to substitutions at glycine 1306, and myotonia plus weakness
      caused by a mutation at threonine 1313. Heterologous expression in HEK cells
      showed that substitutions at either site disrupted inactivation, as reflected by
      slower inactivation rates, shifts in steady-state inactivation, and larger
      persistent Na+ currents. For T1313M, however, the changes were an order of
      magnitude larger than any of three substitutions at G1306, and recovery from
      inactivation was hastened as well. Model simulations demonstrate that these
      functional difference have distinct phenotypic consequences. In particular, a
      large persistent Na+ current predisposes to paralysis due to depolarization
      induced block of action potential generation.

PMID- 8740372
TI  - Ca2+ fluxes and channel regulation in rods of the albino rat.
AB  - By use of microelectrodes, changes in the receptor current and the Ca2+
      concentration were measured in the rod layer of the rat retina after stimulation
      by flashes or steady light. Thereby light induced Ca2+ sources, and sinks along a
      rod were determined in dependence of time. Thus, the Ca2+ fluxes across the
      plasma membrane of a mammalian rod could be studied in detail. By light
      stimulation, Ca2+ sources are evoked along the outer segment only. Immediately
      after a saturating flash, a maximum of Ca2+ efflux is observed which decays
      exponentially with tau = 0.3 s at 37 degrees C (4.2 s at 23 degrees C). During
      regeneration of the dark current, the outer segment acts as a Ca2+ sink,
      indicating a restoration of the Ca(2+)-depleted outer segment. These findings
      agree with earlier reports on amphibian rods. Further experiments showed that the
      peak Ca2+ efflux and tau are temperature dependent. The peak amplitude also
      depends on the external Ca2+ concentration. In contrast to the reports on
      amphibian rods, only a part of the Ca2+ ions extruded from the outer segment is
      directly restored. Surprisingly, during steady light the Ca2+ efflux approaches a
      permanent residual value. Therefore, in course of a photoresponse, Ca2+ must be
      liberated irreversibly from internal Ca2+ stores. There is certain evidence that
      the inner segment acts as a Ca2+ store. Our results show that the Ca2+ fraction
      of the ions carrying the dark current is proportional to the extracellular Ca2+
      concentration. This indicates that the Ca2+ permeability of the plasma membrane
      of the rod outer segment is independent of the Ca2+ concentration.

PMID- 8740373
TI  - Calcium-dependent potentiation of store-operated calcium channels in T
      lymphocytes.
AB  - The depletion of intracellular Ca2+ stores triggers the opening of Ca2+ release
      activated Ca2+ (CRAC) channels in the plasma membrane of T lymphocytes. We have
      investigated the additional role of extracellular Ca2+ (Ca02+) in promoting CRAC
      channel activation in Jurkat leukemic T cells. Ca2+ stores were depleted with 1
      microM thapsigargin in the nominal absence of Ca02+ with 12 mM EGTA or BAPTA in
      the recording pipette. Subsequent application of Ca02+ caused ICRAC to appear in
      two phases. The initial phase was complete within 1 s and reflects channels that
      were open in the absence of Ca02+. The second phase consisted of a severalfold
      exponential increase in current amplitude with a time constant of 5-10 s; we call
      this increase Ca(2+)-dependent potentiation, or CDP. The shape of the current
      voltage relation and the inferred single-channel current amplitude are unchanged
      during CDP, indicating that CDP reflects an alteration in channel gating rather
      than permeation. The extent of CDP is modulated by voltage, increasing from
      approximately 50% at +50 mV to approximately 350% at -75 mV in the presence of 2
      mM Ca02+. The voltage dependence of CDP also causes ICRAC to increase slowly
      during prolonged hyperpolarizations in the constant presence of Ca02+. CDP is not
      affected by exogenous intracellular Ca2+ buffers, and Ni2+, a CRAC channel
      blocker, can cause potentiation. Thus, the underlying Ca2+ binding site is not
      intracellular. Ba2+ has little or no ability to potentiate CRAC channels. These
      results demonstrate that the store-depletion signal by itself triggers only a
      small fraction of capacitative Ca2+ entry and establish Ca2+ as a potent cofactor
      in this process. CDP confers a previously unrecognized voltage dependence and
      slow time dependence on CRAC channel activation that may contribute to the
      dynamic behavior of ICRAC.

PMID- 8740374
TI  - Fast inactivation causes rectification of the IKr channel.
AB  - The mechanism of rectification of HERG, the human cardiac delayed rectifier K+
      channel, was studied after heterologous expression in Xenopus oocytes. Currents
      were measured using two-microelectrode and macropatch voltage clamp techniques.
      The fully activated current-voltage (I-V) relationship for HERG inwardly
      rectified. Rectification was not altered by exposing the cytoplasmic side of a
      macropatch to a divalent-free solution, indicating this property was not caused
      by voltage-dependent block of outward current by Mg2+ or other soluble cytosolic
      molecules. The instantaneous I-V relationship for HERG was linear after removal
      of fast inactivation by a brief hyperpolarization. The time constants for the
      onset of and recovery from inactivation were a bell-shaped function of membrane
      potential. The time constants of inactivation varied from 1.8 ms at +50 mV to 16
      ms at -20 mV; recovery from inactivation varied from 4.7 ms at -120 mV to 15 ms
      at -50 mV. Truncation of the NH2-terminal region of HERG shifted the voltage
      dependence of activation and inactivation by +20 to +30 mV. In addition, the rate
      of deactivation of the truncated channel was much faster than wild-type HERG. The
      mechanism of HERG rectification is voltage-gated fast inactivation. Inactivation
      of channels proceeds at a much faster rate than activation, such that no outward
      current is observed upon depolarization to very high membrane potentials. Fast
      inactivation of HERG and the resulting rectification are partly responsible for
      the prolonged plateau phase typical of ventricular action potentials.

PMID- 8740375
TI  - The dihydropyridine-sensitive calcium channel subtype in cone photoreceptors.
AB  - High-voltage activated Ca channels in tiger salamander cone photoreceptors were
      studied with nystatin-permeabilized patch recordings in 3 mM Ca2+ and 10 mM Ba2+.
      The majority of Ca channel current was dihydropyridine sensitive, suggesting a
      preponderance of L-type Ca channels. However, voltage-dependent, incomplete block
      (maximum 60%) by nifedipine (0.1-100 microM) was evident in recordings of cones
      in tissue slice. In isolated cones, where the block was more potent, nifedipine
      (0.1-10 microM) or nisoldipine (0.5-5 microM) still failed to eliminate
      completely the Ca channel current. Nisoldipine was equally effective in blocking
      Ca channel current elicited in the presence of 10 mM Ba2+ (76% block) or 3 mM
      Ca2+ (88% block). 15% of the Ba2+ current was reversibly blocked by omega
      conotoxin GVIA (1 microM). After enhancement with 1 microM Bay K 8644, omega
      conotoxin GVIA blocked a greater proportion (22%) of Ba2+ current than in
      control. After achieving partial block of the Ba2+ current with nifedipine,
      concomitant application of omega-conotoxin GVIA produced no further block. The P
      type Ca channel blocker, omega-agatoxin IVA (200 nM), had variable and
      insignificant effects. The current persisting in the presence of these blockers
      could be eliminated with Cd2+ (100 microM). These results indicate that
      photoreceptors express an L-type Ca channel having a distinguishing
      pharmacological profile similar to the alpha 1D Ca channel subtype. The presence
      of additional Ca channel subtypes, resistant to the widely used L-, N-, and P
      type Ca channel blockers, cannot, however, be ruled out.

PMID- 8740376
TI  - Removal of extracellular chloride suppresses transmitter release from
      photoreceptor terminals in the mudpuppy retina.
AB  - Removal of extracellular Cl- has been shown to suppress light-evoked voltage
      responses of ON bipolar and horizontal cells, but not photoreceptors or OFF
      bipolar cells, in the amphibian retina. A substantial amount of experimental
      evidence has demonstrated that the photoreceptor transmitter, L-glutamate,
      activates cation, not Cl-, channels in these cells. The mechanism for Cl-free
      effects was therefore reexamined in a superfused retinal slice preparation from
      the mudpuppy (Necturus maculosus) using whole-cell voltage and current clamp
      techniques. In a Cl-free medium, light-evoked currents were maintained in rod and
      cone photoreceptors but suppressed in horizontal, ON bipolar, and OFF bipolar
      cells. Changes in input resistance and dark current in bipolar and horizontal
      cells were consistent with the hypothesis that removal of Cl- suppresses tonic
      glutamate release from photoreceptors. The persistence of light-evoked voltage
      responses in OFF bipolar cells, despite the suppression of light-evoked currents,
      is due to a compensatory increase in input resistance. Focal application of
      hyperosmotic sucrose to photoreceptor terminals produced currents in bipolar and
      horizontal cells arising from two sources: (a) evoked glutamate release and (b)
      direct actions of the hyperosmotic solution on postsynaptic neurons. The inward
      currents resulting from osmotically evoked release of glutamate in OFF bipolar
      and horizontal cells were suppressed in a Cl-free medium. For ON bipolar cells,
      both the direct and evoked components of the hyperosmotic response resulted in
      outward currents and were thus difficult to separate. However, in some cells,
      removal of extracellular Cl- suppressed the outward current consistent with a
      suppression of presynaptic glutamate release. The results of this study suggest
      that removal of extracellular Cl- suppresses glutamate release from photoreceptor
      terminals. Thus, it is possible that control of [Cl-] in and around
      photoreceptors may regulate glutamate release from these cells.

PMID- 8740377
TI  - Functional consequences of lidocaine binding to slow-inactivated sodium channels.
AB  - Na channels open upon depolarization but then enter inactivated states from which
      they cannot readily reopen. After brief depolarizations, native channels enter a
      fast-inactivated state from which recovery at hyperpolarized potentials is rapid
      (< 20 ms). Prolonged depolarization induces a slow-inactivated state that
      requires much longer periods for recovery (> 1 s). The slow-inactivated state
      therefore assumes particular importance in pathological conditions, such as
      ischemia, in which tissues are depolarized for prolonged periods. While use
      dependent block of Na channels by local anesthetics has been explained on the
      basis of delayed recovery of fast-inactivated Na channels, the potential
      contribution of slow-inactivated channels has been ignored. The principal (alpha)
      subunits from skeletal muscle or brain Na channels display anomalous gating
      behavior when expressed in Xenopus oocytes, with a high percentage entering slow
      inactivated states after brief depolarizations. This enhanced slow inactivation
      is eliminated by coexpressing the alpha subunit with the subsidiary beta 1
      subunit. We compared the lidocaine sensitivity of alpha subunits expressed in the
      presence and absence of the beta 1 subunit to determine the relative
      contributions of fast-inactivated and slow-inactivated channel block.
      Coexpression of beta 1 inhibited the use-dependent accumulation of lidocaine
      block during repetitive (1-Hz) depolarizations from -100 to -20 mV. Therefore,
      the time required for recovery from inactivated channel block was measured at 
      100 mV. Fast-inactivated (alpha + beta 1) channels were mostly unblocked within 1
      s of repolarization; however, slow-inactivated (alpha alone) channels remained
      blocked for much longer repriming intervals (> 5 s). The affinity of the slow
      inactivated state for lidocaine was estimated to be 15-25 microM, versus 24
      microM for the fast-inactivated state. We conclude that slow-inactivated Na
      channels are blocked by lidocaine with an affinity comparable to that of fast
      inactivated channels. A prominent functional consequence is potentiation of use
      dependent block through a delay in repriming of lidocaine-bound slow-inactivated
      channels.

PMID- 8740378
TI  - Proper diagnosis: a must before surgery for stress incontinence.
AB  - Stress urinary incontinence is just one of many possible reasons for incontinence
      in a female patient. It is important to determine the exact etiology of the
      urinary incontinence because successful treatment depends on an accurate
      diagnosis. Many additional factors such as age, level of activity, presence and
      degree of pelvic prolapse, detrusor abnormalities, and coexisting medical
      conditions must be considered during the incontinence evaluation. The physical
      examination should assess urethral mobility and genital prolapse abnormalities.
      Bladder storage abnormalities such as poor compliance are accurately assessed
      using current urodynamic methods, but detrusor control abnormalities, such as
      detrusor instability, are not. The urodynamic evaluation is directed toward
      identifying and quantifying urinary leakage attributable to excursions of
      abdominal pressure utilizing abdominal (Valsalva) leak-point pressure testing. A
      focused evaluation allows the appropriate operative procedure to be selected,
      yielding optimal long-term results.

PMID- 8740379
TI  - Anatomic goals in the correction of female stress urinary incontinence.
AB  - The goal of stress incontinence surgery is to prevent opening of the urethra
      during increases in intra-abdominal pressure. Greater refinements in the
      understanding of the pathophysiology of incontinence and experience with newer
      treatments have extended surgical thinking beyond the familiar paradigm "to place
      the urethra in a high retropubic position." When incontinence is associated with
      vaginal hypermobility, vaginal support may be sufficient to restore continence if
      the suburethral vaginal wall is sufficiently strong, an evaluation which must
      often be made by physical examination alone. However, when the vaginal wall is
      weak, the urethra will require an alternative form of support, usually a sling.
      If the urethra is intrinsically deficient, vaginal support may not be sufficient
      to prevent opening during increased intra-abdominal pressure, and coaptation by
      sling obstruction or periurethral bulking injection may be required. Most
      laparoscopic approaches to stress incontinence use Burch's method, which offers
      excellent urethral stability provided the suburethral vaginal wall is strong.
      Newer insights into the relation between vaginal mobility and urethral closure
      are discussed, as well as anatomic aspects of the Burch suspension relevant to
      laparoscopic repair.

PMID- 8740380
TI  - Physiological principles for surgical correction of detrusor dysfunction.
AB  - Urinary incontinence may be the result of various forms of detrusor overactivity.
      Several surgical therapies have been devised, but with the exception of
      procedures to relieve urethral obstruction, none abolishes the overactivity or
      restores normal micturition. In general, ablative neurosurgery is considered only
      in patients with chronic neurologic disease. Bladder augmentation is useful in
      selected patients. The indications for urinary diversion in patients with
      detrusor overactivity and urge incontinence are quite limited.

PMID- 8740381
TI  - Needle suspension procedures: past, present, and future.
AB  - This article reviews the history, evolution, and future of transvaginal needle
      suspension procedures for stress urinary incontinence. Although numerous
      technical modifications to the original Pereyra transvaginal needle suspension
      procedure have been described, the true success rates of these procedures are
      difficult to ascertain. In general, outcomes reported in the literature are
      variable, and few long-term studies exist. Only the results of well-designed,
      prospective, and long-term studies will determine whether recent advances in
      patient selection and continuing technical modifications will improve the outcome
      of bladder neck suspension procedures.

PMID- 8740382
TI  - Vesica percutaneous bladder neck stabilization.
AB  - The Vesica percutaneous bladder neck stabilization (PBNS) represents a minimally
      invasive surgical procedure for the treatment of stress incontinence caused by
      hypermobility of the proximal urethra and bladder neck. Since the initial
      description of the procedure, technique and instrumentation modifications have
      added to the reproducibility of this operation. Three specific modifications have
      been incorporated: strong attachment of the stabilization suture to the pubic
      bone utilizing a bone anchor; incorporation of a full-thickness broad segment of
      tissue including the endopelvic, pubocervical, and subvaginal fascia as well as
      vaginal wall in a Z suture; and loose resuspension of the proximal urethra to
      stabilize the continence mechanism. Cystoscopic verification of suture location
      precludes bladder entry or distal suture placement. This procedure has been
      utilized in 71 women with an overall cure rate (no stress incontinence) of 94% at
      follow-up of 12 months. One retropubic abscess required drainage, and a second
      patient required excision of a skin sinus tract caused by an infected bone
      anchor. Urinary retention longer than 3 weeks has not been encountered. Overall
      morbidity has been minimal. Long-term follow-up of continence status and other
      procedure-related complications is ongoing. The PBNS provides continence results
      and complication rates equivalent to those of other retropubic and transvaginal
      procedures using a minimally invasive outpatient technique.

PMID- 8740383
TI  - Use of synthetic material in sling surgery: a minimally invasive approach.
AB  - Traditionally, autologous material has been favored over synthetic material in
      the construction of pubovaginal slings for the treatment of female stress urinary
      incontinence (SUI). This preference arose largely because of concern about an
      increased incidence of infection or sling erosion when synthetic materials are
      used. However, when care is taken to minimize the amount of synthetic material,
      reduce total operative time, and limit exposure of the material to the operative
      field, female SUI can be treated effectively with synthetic material with an
      acceptably low complication rate. Furthermore, utilization of slings constructed
      with artificial graft material can be minimally invasive, cost effective, and
      well tolerated.

PMID- 8740384
TI  - Transvaginal correction of pelvic prolapse.
AB  - Pelvic prolapse has a myriad of clinical manifestations ranging from urethral
      incontinence to total vault prolapse. The evaluation and treatment of these
      conditions is facilitated by dividing them into three anatomic regions. Anterior
      vaginal wall prolapse is the most common type and includes simple urethral
      hypermobility as well as severe cystocele. Surgical treatment includes the
      modified anterior vaginal wall sling, six-corner bladder neck suspension, and
      formal cystocele repair. Posterior vaginal wall prolapse, manifested by rectocele
      and perineal relaxation, is corrected by plication of the prerectal and
      pararectal fascia, reconstruction of the levator hiatus, and repair of the
      perineal body. Vault prolapse includes enterocele, uterine prolapse, and
      generalized vault prolapse. The choice of treatment depends on the presence of
      anterior vaginal wall prolapse, the degree of vault prolapse, and the patient's
      desire to remain sexually active. It is important to remember that urethral
      incontinence is only one manifestation of pelvic prolapse, and must be treated in
      conjunction with other prolapse to avoid recurrence or poor results.

PMID- 8740385
TI  - Correction of stress urinary incontinence: transperitoneal approach.
AB  - The options available to correct stress urinary incontinence are numerous. We
      reviewed the current literature on transperitoneal laparoscopic surgery as a new
      minimally invasive alternative for the correction of this problem.
      Transperitoneal laparoscopic colposuspension is technically feasible and has a
      success rate comparable to that of the traditional open retropubic urethropexy
      and transvaginal needle suspension techniques. Laparoscopic repair takes longer
      to complete but minimizes postoperative discomfort, hospital stay, and the time
      to return of normal activities. There is little blood loss, and the duration of
      urinary diversion averages 24 to 48 hours, with suprapubic urinary drainage
      unnecessary. Laparoscopic colposuspension by the transperitoneal approach is a
      reasonable alternative in treating stress urinary incontinence. Early results are
      similar to those of open and needle suspension techniques, although longer follow
      up is necessary to determine long-term efficacy.

PMID- 8740386
TI  - Correction of stress urinary incontinence: retropubic approach.
AB  - Urinary incontinence affects more than 10,000,000 Americans, a significant number
      of whom have stress urinary incontinence. Laparoscopic bladder neck suspension is
      an increasingly common treatment for this disorder. Performed by an
      extraperitoneal approach, this operation takes significantly longer than a
      transvaginal operation; but the postoperative analgesic requirements, period of
      urinary diversion, and hospital stay are far less, and the success rates are
      similar. Randomized trials and longer follow-up are necessary to substantiate the
      preliminary encouraging results of the laparoscopic operation.

PMID- 8740387
TI  - Correction of stress urinary incontinence: laparoscopy combined with vaginal
      suturing.
AB  - The authors review the published techniques of laparoscopic colposuspension
      combined with vaginal suturing. Particular emphasis is given to their own
      technique, first published in 1992, and to that of Harewood (1993), which is
      similar. Both involve a Burch-like colposuspension using a technique similar to
      that of Gittes and Loughlin. This is possible looking inside the pelvis through a
      laparoscope and using a handle-needle. Published results are similar (about 70%
      success rate), but the authors point out that the Breda technique is simpler,
      cheaper, and less time consuming (only one trocar instead of three) and has had a
      longer follow-up (up to 3 years instead of 19 months). The authors review many
      other similar techniques reported between 1993 and 1995 with good results but
      based on rather limited experience. The conclusion is that the laparoscopic
      technique with vaginal suturing seems a promising way to approach stress urinary
      incontinence in the female patient.

PMID- 8740388
TI  - Laparoscopic urethral sling for treatment of intrinsic sphincter deficiency.
AB  - The surgical treatment of intrinsic sphincter deficiency, or Type III genuine
      stress urinary incontinence, has traditionally been accomplished by sling
      cystourethropexy, the placement of an artificial urinary sphincter, or
      periurethral injection. We developed a laparoscopic approach for the performance
      of a sling cystourethropexy as an alternative to the open approach and herein
      describe our experience. We have found that a laparoscopic sling cystourethropexy
      is feasible, but at the present time, we have been unable to demonstrate any
      significant advantages to the patient in terms of decreased cost or convalescence
      compared with the open vaginal sling cystourethropexy.

PMID- 8740389
TI  - Correction of genital prolapse.
AB  - Massive eversion of the vagina is one of the most disturbing disorders
      confronting a woman. It is a complex disorder that always coexists with other
      pelvic floor defects. The management is almost always surgical, and all defects
      must be repaired concomitantly. Current surgical practice relies primarily on the
      strength of the endopelvic fascia and certain ligaments, which clearly is not
      ideal for providing the kind of support needed. Current understanding of the
      neurophysiology, neuroanatomy, and biophysics of the pelvic floor give us hope
      that management will be more effective in the future. Laparoscopic repair
      techniques are described.

PMID- 8740390
TI  - Laparoscopic bladder seromyotomy: laboratory experience.
AB  - Twelve female microminipigs with normal bladder capacity underwent laparoscopic
      bladder seromyotomy. Three other female microminipigs were added to the study as
      controls. Urodynamic studies and cystograms were performed preoperatively and at
      2 and 4 months after a laparoscopic bladder seromyotomy. Histologic studies of
      the treated bladders were performed when the animals were euthanized at 4 months.
      The operation was completed in all 12 test animals. There was no significant
      difference in bladder capacity or leak-point pressure between the 12 seromyotomy
      and the 3 control bladders at any time point. Histologically, over the
      seromyotomy site, the urothelium remained intact; however, the muscularis was
      attenuated, and a thin layer of fibrotic tissue replaced the normal serosal
      covering of the bladder. Laparoscopic bladder seromyotomy can be performed
      reliably in the porcine animal model. Not surprisingly, no significant changes in
      bladder capacity or bladder compliance were seen in our study of normal bladders.
      An animal model of a neuropathic contracted bladder is needed to assess more
      accurately the physiological impact of laparoscopic seromyotomy.

PMID- 8740391
TI  - Rationale and treatment results with bioinjectables.
AB  - Management of intrinsic sphincter deficiency (ISD) can be achieved by many
      techniques. Those patients suffering from urinary incontinence secondary to ISD
      have often undergone multiple prior procedures for management of incontinence;
      therefore, an ideal form of treatment would be one that is minimally invasive and
      safe without compromising efficacy. The bioinjectables have proved to be safe and
      effective for the management of ISD and offer a minimally invasive alternative
      that can be performed under local anesthesia. This form of therapy is especially
      advantageous for properly selected patients suffering from urinary incontinence
      caused by ISD. We review the properties, indications for use, and results of the
      bioinjectables used in the treatment of ISD.

PMID- 8740392
TI  - Antegrade collagen injection for stress incontinence after radical prostatectomy:
      technique and early results.
AB  - This article describes the technique and early results of antegrade collagen
      injection into the bladder neck and proximal urethra of men with stress
      incontinence postprostatectomy. Twenty men underwent collagen injection under
      general anesthesia. Follow-up ranges from 5 to 15 months, with a mean of 9.5
      months. A mean of 14.5 cc of collagen was injected (range 5-25 cc). According to
      a subjective self-grading system, preoperative and postoperative urodynamics, and
      pad usage before and after treatment, significant improvement was seen in 14
      patients (70%), and subjective cure was reported by 5 (25%). Six patients (30%)
      had no subjective or objective improvement after the injection. The antegrade
      collagen injection technique is a promising and simple method of correcting
      postprostatectomy stress urinary incontinence. Further study and longer follow-up
      is necessary to determine its precise role in the treatment of men with this
      problem.

PMID- 8740393
TI  - Periurethral injection of the genitourinary spheroidal membrane.
AB  - Periurethral injection of bulking agents to cause coaptation of the urethral
      walls has long been used in the treatment of urinary incontinence. A new form of
      this treatment is the silicone Genitourinary Spheroidal Membrane (Genisphere),
      which is placed in the periurethral tissues with a special delivery tool. Among
      39 women who received two or three Genispheres, 29 (77%) became dry or markedly
      improved with a significant increase in leak-point and proximal urethral closure
      pressures. Early sexual activity, a short urethra, atrophic tissue, bladder
      instability, incorrect positioning, and device rupture were the causes of
      failure. The device has several advantages over traditional bulking agents,
      including the absence of silicone particles that can migrate, and has proved to
      be a safe method of treating stress urinary incontinence.

PMID- 8740394
TI  - Treatment with the Reliance urinary control insert: one-year experience.
AB  - The 1-year experience of 63 women using an intraurethral insert for the
      management of stress or mild mixed urinary incontinence is presented, emphasizing
      safety and efficacy. Objective criteria, including standardized pad weight tests
      and patient diaries, were employed to evaluate the device's effectiveness. At
      study outset, 82% of the patients were completely dry with the device in situ,
      with an additional 16% of patients significantly improved. At 12 months, 79% of
      the patients were completely dry, and 16% were significantly improved. This
      result is consistent with the significant improvement (P < 0.0001) in the number
      of urinary incontinence episodes reported in patient diaries. Women reported that
      the device significantly improved their ability to stay dry over a number of
      routine and physically demanding daily activities. The device was increasingly
      easy to use and more comfortable over time (P < 0.0001). The latter finding was
      confirmed by a decline in patient reports of "sensation of device presence" over
      the duration of the study (35% at 1 week v 7% at 12 months). Untoward events
      included gross hematuria (24%), device-related bladder mucosal irritation (9%),
      and symptomatic bacteriuria (30%). Such side effects were expected for this type
      of device, were easily managed without significant medical intervention, and did
      not result in any long-term clinical sequelae. The great reduction in the number
      of episodes of urinary incontinence, the low rate of significant problems
      associated with device use, and ease of use make the intraurethral insert a
      useful management alternative for women with stress urinary incontinence.

PMID- 8740395
TI  - Introl bladder neck support prosthesis: a nonsurgical urethropexy.
AB  - The Bladder Neck Support Prosthesis is a Silastic vaginal device designed to
      elevate and support the bladder neck and proximal urethra during stressful
      physical activities. It mimics the effects of a urethropexy on urethral function
      without resulting in urinary outflow obstruction. Recent clinical studies in
      women with stress and mixed incontinence have demonstrated significant objective
      reductions in involuntary urine loss and high subjective satisfaction ratings.

PMID- 8740396
TI  - Nursing assessment and management strategies for urinary incontinence.
AB  - The promotion of continence is a multidisciplinary responsibility, with the nurse
      specialist's focus being on management, education, and ensuring a team approach.
      The patient's cognitive and functional abilities, general medical condition, and
      informed choice will ultimately determine the management plan. Behavioral
      techniques, supportive devices and intermittent catheterization are among the low
      risk interventions available to treat patients.

PMID- 8740397
TI  - Abnormal circulating pancreatic enzyme activities in more than twenty-five
      percent of recent-onset insulin-dependent diabetic patients: association of
      hyperlipasemia with high-titer islet cell antibodies. Belgian Diabetes Registry.
AB  - Pancreatic amylase and lipase activities were measured in sera of 307 Caucasian
      insulin-dependent diabetes mellitus patients (IDDM) at clinical onset, 303
      nondiabetic siblings of registered patients, and 207 control subjects under age
      40 years. In all subject groups lipasemia and pancreatic (but not salivary)
      amylasemia increased with age and were significantly correlated. Using age
      dependent reference ranges, reduced pancreatic enzyme levels were measured in 18%
      of patients, 6% of siblings, and only 2% of control subjects (p < 0.001).
      Increased lipase levels were noted in 10% of patients and in only 3% of siblings
      and 2% of control subjects (p < 0.001). Using both univariate and multivariate
      statistical analysis, elevated lipase activities at clinical onset were
      associated with higher titers of autoantibodies against islet cell cytoplasmic
      antigens and glucagon, but not against insulin or the 65-kDa isoform of glutamic
      acid decarboxylase (GAD65-Ab), or with markers of genetic predisposition or
      metabolic dysregulation. These findings indicate the presence of modest, but
      statistically significant, variations in circulating pancreatic enzyme levels in
      28% of IDDM patients at clinical onset (p < 0.001 vs. 5% in control subjects).
      Increased lipase levels may express a form or a stage of the disease with
      exocrine cell damage; their association with higher titers of islet cell and
      glucagon autoantibodies is not yet explained. Lower lipase and isoamylase levels
      are thought to result from the reduced acinar cell function in the vicinity of
      insulin-depleted islets. It must be tested whether pancreatic enzyme activities
      in serum can also be altered during the preclinical stage and can thus be
      considered as an additional marker for the disease process in the pancreas.

PMID- 8740398
TI  - Effects of certain growth factors on in vitro maturation of rat fetal islet-like
      structures.
AB  - We have previously studied the expression of protein tyrosine kinases in
      different preparations of insulin producing cells by polymerase chain reaction
      (PCR). Among the tyrosine kinases thus identified were the fibroblast growth
      factor receptor-4 (FGFR-4), c-Kit, the insulin-like growth factor (IGF-I)
      receptor, and the cytoplasmic tyrosine kinase Jak2, which associates with the
      activated receptor for growth hormone (GH). To elucidate the putative biological
      effects of the receptors identified, fetal islet-like structures were cultured in
      the absence or presence of the ligands to the receptors identified, namely,
      acidic FGF (aFGF), stem-cell factor (SCF), IGF-I, and GH, whereafter insulin and
      DNA contents as well as insulin secretion to the culture medium were determined.
      Nerve growth factor (NGF), the ligand to the tyrosine kinase receptor Trk-A, was
      also included. aFGF and GH were found to stimulate insulin release to the culture
      medium, whereas SCF augmented insulin contents/DNA as well as islet DNA contents.
      No effects of NGF or IGF-I were detected. Immunohistochemical studies of fetal
      rat pancreas showed localization of the c-Kit protein to the pancreatic ducts,
      whereas immuno-reactivity against FGFR-4 could be detected in both endocrine and
      exocrine parts of the pancreas as well as in the pancreatic ducts. It is
      concluded that tyrosine kinase receptors may be involved in the maturation of
      pancreatic beta cells.

PMID- 8740399
TI  - The role of zinc in solutions used for cold preservation of pancreatic islets.
AB  - Advances in the field of organ transplantation have been made possible by
      progress in cold preservation as well as advances in immunosuppression,
      postoperative surgical care, and refinement of surgical techniques. The optimal
      solution for cold storage of pancreatic islets has not been defined, although
      recent studies have suggested that University of Wisconsin (UW) solution or
      derivatives may be significant advances. Zinc has a central role in the storage,
      synthesis, and secretion of insulin and is taken up preferentially by isolated
      islets to levels 30-fold higher than those of extracellular zinc. Since the
      currently used cold storage solutions do not contain zinc, we have investigated
      the effect of adding zinc to Hanks and UW solution and assessed the viability
      status of the islets at 0 h and at 1, 3, and 6 days. Islets of standard diameter
      were suspended in four solutions: Hanks solution, Hanks +20 microM zinc, UW
      solution, and UW +20 microM zinc. Viability was assessed by supravital staining,
      and each islet was scored at 0 h and at 1, 3, and 6 days. The results showed that
      UW solution was superior to Hanks solution for the preservation of pancreatic
      islets up to 6 days, but the addition of zinc was not beneficial. Despite the
      integral role of zinc in islet metabolism, we were unable to find a beneficial
      role for zinc in cold storage solutions for the purposes of islet preservation.

PMID- 8740400
TI  - Exogenous insulin does not influence CCK- and meal-stimulated pancreatic
      secretion.
AB  - Although previous reports suggest interactions between the endocrine and the
      exocrine pancreas, insulin's effect on pancreatic exocrine function remains
      unclear. Chronic pancreatic fistulae were created in five dogs; these animals
      were studied using the euglycemic, hyperinsulinemic clamp technique. After a 30
      min unstimulated period, both groups received a 60-min, 1.5 mU/kg/min insulin
      (clamp) or vehicle (control) infusion. Cholecystokinin (CCK) or meal stimulation
      was then begun. Intravenous CCK was initiated at 12.5 ng/kg/h; the CCK dose was
      doubled every 30 min until 100 ng/kg/h was achieved. The intraduodenal liquid
      test meal (1.5 kcal/ml; 15% protein, 32% fat, 53% carbohydrate) was administered
      at 100 ml/h. Unstimulated (0- to 30-min) serum glucose and insulin levels and
      pancreatic bicarbonate and protein outputs did not differ between groups. Clamp
      (30- to 90-min) and stimulated (90- to 210-min) insulins were significantly
      elevated in clamp groups (p < 0.001); glucose and bicarbonate were unchanged.
      Exocrine outputs during clamp periods were unaffected by insulin. Neither CCK-
      nor meal-stimulated pancreatic secretion (90-210 min) was influenced by insulin
      administration. These data suggest that hyperinsulinemia does not alter
      pancreatic acinar cell secretion in the intact animal.

PMID- 8740401
TI  - Role of cholecystokinin (CCK)-A receptor for pancreatic growth after weaning: a
      study in a new rat model without gene expression of the CCK-A receptor.
AB  - This work extends a recent observation that Otsuka Long-Evans Tokushima Fatty
      (OLETF) rats, which have been established as an animal model of non-insulin
      dependent diabetes mellitus, show no expression of the cholecystokinin (CCK)-A
      receptor gene in the pancreas. The CCK-A receptor is known to be involved in
      regulating pancreatic exocrine function and growth. We examined the growth of the
      pancreas in terms of wet weight, enzyme compositions, and protein and DNA
      contents at 5-6 and 24-25 weeks of age in OLETF rats and control (Long-Evans
      Tokushima; LETO) rats. The pancreatic wet weight increased significantly with age
      in both OLETF and LETO rats but was significantly lower in OLETF rats than in
      LETO rats. The total DNA contents in the whole pancreas (cell numbers) were
      comparable for both strains and increased significantly with age. However, the
      ratio of protein content to DNA content (the cell size) significantly increased
      with age in LETO rats, with no increase in OLETF rats. The changes in
      chymotrypsin, amylase, and insulin with respect to age were in the same direction
      in both strains: a decrease or no change in total and/or cellular contents of
      chymotrypsin and insulin and increases in amylase. These results suggest that the
      CCK-A receptor plays some role in the increase in cell size associated with
      normal growth of the pancreas from 5 to 25 weeks of age (after weaning).

PMID- 8740402
TI  - Clinical significance of carcinoma invasion of the extrapancreatic nerve plexus
      in pancreatic cancer.
AB  - To elucidate the clinical significance of neural invasion in pancreatic
      carcinoma, a clinicopathological study was performed. Neural invasion is a common
      feature of pancreatic carcinoma whose clinical significance has not yet been
      determined. Over a period of > 10 years, 129 of 204 (63%) patients with
      pancreatic carcinoma underwent resection by extensive radical surgery. A
      clinicopathological study of those specimens of pancreatic carcinoma was
      performed, with particular reference to neural invasion. Intrapancreatic neural
      invasion was observed in 116 of 129 (90%), of which 80 (69%) showed
      extrapancreatic nerve plexus involvement. A statistically significant (p < 0.001)
      correlation between the grade of intrapancreatic neural invasion and
      extrapancreatic nerve plexus invasion was observed. The postoperative survival
      rate for patients with extrapancreatic nerve plexus involvement was significantly
      (p < 0.001) lower than that for patients without extrapancreatic nerve plexus
      involvement. Patients who survived for > 3 years after operation had no
      extrapancreatic nerve plexus invasion even when portal vein wall invasion was
      observed.

PMID- 8740403
TI  - K-ras mutation and p53 protein accumulation in intraductal mucin-hypersecreting
      neoplasms of the pancreas.
AB  - Intraductal mucin-hypersecreting neoplasm of the pancreas (IMHN) is a unique
      tumor that is composed of tumor cells with different cell atypia. K-ras and p53
      alterations have been shown to occur in pancreatic duct cell carcinoma (PDC), but
      they have not been well documented in the individual lesion of IMHN. The aim of
      this study was to examine the relation of the genetic alterations of K-ras and
      p53 in IMHN to the tumorigenesis of the pancreas. In 32 microscopically dissected
      lesions of seven cases of IMHN, the K-ras mutation was investigated by primer
      mediated, mutant-enriched, polymerase chain reaction-restriction fragment length
      polymorphism. Mutant p53 expression was examined in the adjacent serial sections
      by immunohistochemistry. In IMHN, alterations of K-ras and p53 were frequently
      observed (71.9 and 50%, respectively). The frequency became higher as the grade
      of cell atypia increased. Simultaneous alterations of the two genes were detected
      in carcinoma and its accompanying hyperplastic and dysplastic lesions. It is
      suggested that alterations of K-ras and p53 may be early events in the
      tumorigenesis of IMHN and may cooperate to produce neoplastic transformation of
      the pancreatic duct epithelium.

PMID- 8740404
TI  - Histopathologic study of coexistent pathologic states in pancreatic fibrosis in
      patients with chronic alcohol abuse: two distinct pathologic fibrosis entities
      with different mechanisms.
AB  - The distribution and clinicopathologic features of pancreatic fibrosis were
      studied histopathologically in 137 autopsy cases of chronic alcohol abuse.
      Fibrosis was observed in 90 of the cases and was classified as perilobular
      sclerosis (PS) and intralobular sclerosis (IS). Fibrosis of the PS type was
      irregular and sometimes patchy and extended into the intralobular area in
      advanced cases. In some advanced cases, complete replacement of the pancreatic
      tissue by extensive fibrosis was seen. Fibrosis of the IS type was uniformly
      distributed. The tissues in some cases showed prominently periacinar fibrosis. In
      these cases, the pancreatic parenchyma had not been completely replaced by
      extensive fibrosis. Clinicopathologic comparisons revealed the following results:
      accompanying liver cirrhosis was greater in the IS than in the PS of fibrosis.
      However, a higher frequency of protein plugs, pancreatic stones, extensive
      fibrosis replacement, peripancreatic fibrosis, splenic vein involvement,
      choledochus involvement, pseudocyst, and ductal hyperplasia was found in the PS
      type compared to the IS type. In conclusion, the findings on the perilobular and
      intralobular distribution of fibrosis and differences in various components or
      accompanying diseases in pancreatic fibrosis suggest that this entity shows two
      distinct pathologic patterns with differing mechanisms.

PMID- 8740405
TI  - The need for standardized pathologic staging of pancreaticoduodenectomy
      specimens.
AB  - A standardized method for pathologic evaluation and staging of
      pancreaticoduodenectomy (PD) specimens is critical for accurate reporting of the
      number and location of lymph nodes and margins of resection. We examined the
      impact of standardized pathologic evaluation (SPE) of PD specimens on the
      identification of regional lymph nodes and describe our detailed system for the
      pathologic analysis of the PD specimen. Forty consecutive patients underwent PD
      for histologically confirmed adenocarcinoma of the pancreatic head between April
      1990 and August 1993. Fifteen consecutive specimens were examined before the
      introduction of the SPE, and 25 consecutive specimens underwent SPE. Resection
      margins were evaluated by frozen-section analysis, and then the specimen was
      divided into six regions on an anatomic dissection board for lymph node
      identification. The 25 specimens examined according to the SPE had a
      significantly increased number of lymph nodes identified (P = 0.0001) compared
      with the 15 specimens examined without the SPE. Twelve of the 25 specimens
      contained positive lymph nodes, 6 of which were confined to the
      pancreaticoduodenal region. No positive nodes were found in the periaortic
      region. There were no differences in pathologic variables between patients found
      to have negative and those with positive regional lymph nodes. SPE of PD
      specimens provides a method for improved lymph node identification, ensures
      accurate prospective evaluation of margins of resection, and provides a complete
      analysis of potentially important pathologic variables. We offer this system as a
      standardized model for groups engaged in protocol-based clinical research
      examining innovative multimodality treatment strategies for patients with
      resectable pancreatic cancer.

PMID- 8740406
TI  - Labeled granulocyte scanning for the diagnosis of infected necrosis in acute
      pancreatitis: what kind of labeling should be used?
AB  - Clinical and laboratory data or imaging results cannot provide a positive
      diagnosis of septic complications of pancreatic and peripancreatic necrosis in
      patients with acute pancreatitis. Confirmation can be obtained only after
      percutaneous computed tomography (CT)-guided aspiration of the necrotic tissues
      or fluid collection; although the important role of 99Tc(m)-HMPAO-labeled
      granulocyte scintigraphy has been recently emphasized. The aim of this study was
      to determine the sensitivity and specificity of 99m-technetium
      hexamethylpropyleneamine oxime (99Tc(m)-HMPAO)- or 111In-oxine-labeled
      granulocyte scintigraphy for the diagnosis of infection in pancreatic or
      peripancreatic necrosis to define the ideal label for diagnosis. Thirty-six
      scintigraphic examinations were performed in 34 consecutive patients (mean age,
      58 +/- 2 years) 20 +/- 2 days after the onset of acute pancreatitis (Balthazar
      classes A-C, n = 7; classes D and E, n = 29). The scintigraphic study included
      scintigraphic tomography and static acquisition 1 and 3 h, respectively, after
      reinjection of the autologous 99Tc(m)-labeled granulocytes and static images 3-4
      and 24 h after the simultaneous reinjection of 111In-oxine-labeled autologous
      granulocytes. The diagnosis of infected pancreatic or peripancreatic necrosis was
      confirmed with percutaneous CT-guided aspiration (14 positive aspirates among 20
      performed) and sterile necrosis after negative aspiration (6 negative aspirates)
      or after a 6 +/- 1-month follow-up free of clinical or biological signs of
      ongoing sepsis. The sensitivity and specificity were 86 and 73%, respectively,
      for scintigraphic tomography, 100 and 55% for 3-h 111In images, 93 and 68% for 3
      4-h 111In images, and 100 and 64% for 24-h 111In images. The fall in splenic
      activity between the 3-4 and the 24-h 111In images was 26 +/- 3% in patients with
      septic pancreatic and peripancreatic necrosis (n = 14) and 16 +/- 3% in those
      with sterile necrosis (n = 22) (p < 0.01). Labeled granulocyte scintigraphy was
      thus shown to be an effective tool for the diagnosis of infection in pancreatic
      and/or peripancreatic necrosis due to acute pancreatitis, especially when the
      scintiscans are performed early after injection of 99Tc(m) or when the fall in
      splenic activity over the 24 h following reinjection of 111In is measured in
      particularly difficult cases. These promising preliminary results should be
      confirmed by a prospective study.

PMID- 8740407
TI  - Carboxylic ester hydrolase and amylase in ischemic pancreatitis in the guinea
      pig.
AB  - The observation that an elevated level of pancreatic carboxylic ester hydrolase
      (CEH) in serum is a more sensitive and specific marker of acute pancreatitis than
      is elevated serum amylase activity prompted us to explore whether these findings
      could be confirmed in an experimental model and, if so, to find the explanation
      behind this difference. We therefore developed a model for ischemic pancreatitis
      in the guinea pig and a sandwich enzyme-linked immunosorbent assay for
      determination of CEH in this species. There was a strong correlation between
      duration of ischemia and severity of pancreatic inflammation and between severity
      of inflammation and serum CEH level. In contrast, serum amylase was elevated only
      in animals with the most severe grade of inflammation. Amylase was, however,
      increased in urine in animals with mild inflammation, but the level did not
      increase with severity of inflammation. Only one of 31 animals had detectable CEH
      in urine. In animals with intermediate serum CEH levels the serum and biliary
      concentrations correlated, indicating that CEH may be cleared by the liver.
      Amylase was detectable in bile only in animals with high serum levels. The
      results confirm our observations made in previous clinical studies. A likely
      explanation for differences in serum levels of CEH and amylase is clearance from
      the circulation at different rates and, at least partly, via different routes,
      e.g., the liver and kidney, respectively.

PMID- 8740408
TI  - Histamine-evoked potassium release in the mouse and guinea pig pancreas.
AB  - An investigation was made of the effects of histamine on the K+ concentration in
      the effluent in superfused guinea pig and mouse pancreatic segments. The effect
      of acetylcholine (ACh) was examined for comparison. Histamine evoked a dose
      dependent and transient increase in the K+ concentration in the effluent (K+
      release) but is less potent compared to the cholinergic agonist, ACh. At the same
      doses histamine and ACh evoke a much larger K+ release from mouse superfused
      pancreatic segments followed in the poststimulus period by a reuptake of K+.
      However, this reuptake of K+ was not observed in guinea pig superfused pancreatic
      segments. On the other hand, the cholinergic antagonist, atropine, completely
      abolished the K+ release in response to ACh and histamine from mouse and guinea
      pig pancreatic segments. Our results show the involvement of histamine in the
      control of K+ release in pancreatic tissue, with significant differences in the
      observed responses between species.

PMID- 8740409
TI  - Adenovirus-mediated in vivo gene transfer and expression in normal rat pancreas.
AB  - Gene transfer into the pancreas would be useful for the treatment of a variety of
      disorders, including cystic fibrosis, diabetes, cancer, and immunomodulation of
      pancreatic allografts. A hypothesis that various cell populations in the pancreas
      could be targeted by recombinant adenoviruses was developed and tested. Gene
      transfer into the rat ductal epithelium, acinar cells, and islets of Langerhans
      was accomplished with a recombinant adenovirus containing bacterial beta
      galactosidase by retrograde delivery of adenovirus into the pancreaticobiliary
      duct. Maximal gene expression was observed at 3 days and correlated with DNA blot
      analysis. Histologic analysis of sections from pancreatic tissue in the
      adenovirus-treated rats demonstrated severe pancreatitis. Immunophenotyping of
      the inflammatory infiltrate with rat lymphocyte-specific markers showed CD45-,
      CD8-, and CD4-positive cells. Tissue injury resolved as gene expression was lost,
      with both features absent by 21 days. Pancreatic regeneration was documented by
      the presence of 5-bromo-2'-deoxyuridine-positive staining cells. Pancreatic gene
      transfer with first-generation recombinant adenoviruses can be accomplished by
      techniques applicable to clinical situations. The use of first-generation
      recombinant adenoviruses for pancreas-directed gene transfer is limited by the
      development of inflammation and transient expression.

PMID- 8740410
TI  - Serum Ca 19.9 levels in thalassemia major.

PMID- 8740411
TI  - Tuberculous and nontuberculous mycobacterial infection of the pancreas in a
      patient with AIDS.

PMID- 8740412
TI  - Thrombotic thrombocytopenic purpura caused by acute pancreatitis in a woman with
      a pancreas divisum: a case report.

PMID- 8740413
TI  - Extensive invasion of a ductal adenocarcinoma into the wall of a pancreatic
      pseudocyst.

PMID- 8740414
TI  - Congenital true pancreatic cysts in young adults: case report and literature
      review.

PMID- 8740415
TI  - Flocculation of the yeast Candida famata (Debaryomyces hansenii): an essential
      role for peptone.
AB  - Aggregation of Candida famata (Debaryomyces hansenii) is consistent with being a
      form of lectin-mediated yeast flocculation. Flocculation of C. famata is unusual
      in that it requires the presence of peptone, either in the growth medium or added
      later to harvested cells in buffer. Flocculation after peptone addition was
      rapid, being largely complete within 10 min. Heat-killed cells also flocculated,
      arguing for direct participation of peptone in the flocculation binding
      mechanism. Flocculent C. famata cells progressively lost the ability to
      flocculate when washed with EDTA. Flocculation was fully restored by peptone
      addition; calcium addition was without effect. C. famata cells were able to
      agglutinate erythrocytes in the presence or absence of peptone. Pronase E-treated
      yeast lost both the ability to haemagglutinate and self-flocculate.
      Haemagglutination was not diminished by progressive EDTA washing, suggesting that
      surface lectins remained present and active on the yeast cell walls. Non
      flocculating C. famata cells mutually flocculated with non-flocculent
      Schizosaccharomyces pombe cells, shown to have surface-exposed galactose
      residues. Mutual flocculation was lost following treatment of C. famata with
      Pronase E. It was concluded that the cell wall of C. famata contains lectins
      enabling haemagglutination and mutual flocculation but lacks carbohydrate
      receptors for these lectins. This yeast self-flocculates only via bridging multi
      valent carbohydrates; these being present in peptone.

PMID- 8740416
TI  - Yeast protein translocation complex: isolation of two genes SEB1 and SEB2
      encoding proteins homologous to the Sec61 beta subunit.
AB  - A yeast gene (cDNA clone) was isolated in a screen for suppressors of secretion
      defective sec15-1 mutation. This gene encodes a protein homologous to the beta
      subunit of the mammalian Sec61 protein complex functioning in protein
      translocation into the endoplasmic reticulum (ER). The predicted protein, Seb1p,
      consists of 82 amino acids and contains one potential membrane-spanning region at
      the C-terminus but no N-terminal signal sequence. Seb1p shows 30% identity to the
      mammalian Sec61 beta subunit and 34% identity to the Arabidopsis thaliana Sec61
      beta subunit. Overexpression of SEB1 from a multicopy plasmid suppressed the
      temperature sensitivity of sec61-2 and sec61-3 mutants. Immunofluorescence and
      immunoelectron microscopy indicated that Seb1p resides in the ER membranes with
      the hydrophilic N-terminus exposed to the cytoplasm. The in vitro translated
      Seb1p was post-translationally inserted into microsomal membranes. As the
      chromosomal disruption of the SEB1 gene was not lethal, potential homologous
      genes were screened by heterologous hybridization. The SEB1 homologue thus
      isolated, SEB2, encodes a protein 53% identical to Seb1p. Disruption of the
      chromosomal SEB2 was not lethal whereas the double disruption of SEB1 and SEB2
      resulted in a temperature-sensitive phenotype. This study further emphasizes the
      evolutionary conservation of the ER protein translocation apparatus and provides
      novel genetic tools for its functional analysis.

PMID- 8740417
TI  - High-affinity glucose uptake in Saccharomyces cerevisiae is not dependent on the
      presence of glucose-phosphorylating enzymes.
AB  - Glucose uptake in Saccharomyces cerevisiae is believed to consist of two
      kinetically distinguishable components, the affinity of which is modulated during
      growth on glucose. It has been reported that triple hexose-kinase deletion
      mutants do not exhibit high-affinity glucose uptake. This raises the question of
      whether and how high-affinity glucose uptake is related to the presence of
      glucose-phosphorylating enzymes. In this study the kinetics of glucose uptake in
      both wild-type cells and cells of hexose-kinase deletion mutants, grown on either
      glycerol or galactose, were determined using a rapid-uptake method. In wild-type
      cells glucose uptake measured over either 5 s or 200 ms exhibited high affinity.
      In contrast, in cells of hexose-kinase deletion mutants the apparent affinity of
      glucose uptake was dependent on the time scale during which uptake was measured.
      Measurements on the 5-s scale showed apparent low-affinity uptake whereas
      measurements on the 200-ms scale showed high-affinity uptake. The affinity and
      maximal rate of the latter were comparable to those in wild-type cells. Using a
      simple model for a symmetrical facilitator, it was possible to simulate the
      experimentally determined relation between apparent affinity and the time scale
      used. The results suggest that high-affinity glucose transport is not necessarily
      dependent on the presence of glucose-phosphorylating enzymes. Apparent low
      affinity uptake kinetics can arise as a consequence of an insufficient rate of
      removal of intracellular free glucose by phosphorylation. This study underlines
      the need to differentiate between influences of the translocator and of
      metabolism on the apparent kinetics of sugar uptake in yeast.

PMID- 8740418
TI  - Candida albicans phosphatidylinositol synthase has common features with both
      Saccharomyces cerevisiae and mammalian phosphatidylinositol synthases.
AB  - Phosphatidylinositol (PI) synthase (cytidine 5'-diphospho (CDP)-1,2-diacyl-sn
      glycerol:myo-inositol 3-phosphatidyltransferase, EC 2.7.8.11) was isolated from
      the microsomal cell fraction of Candida albicans. The Triton X-100 extracted
      enzyme was enriched 140-fold by affinity chromatography on CDP-diacylglycerol
      Sepharose. The enzyme had a pH optimum at 9.5 in glycine/NaOH buffer. It had an
      absolute requirement for Mg2+ or Mn2+ and was inhibited by Ca2+ and Zn2+. Maximal
      activity was at 0.2-0.6 mM-CDP-diacylglycerol, higher concentrations inhibited
      the enzyme. With 2'-deoxy-CDP-diacylglycerol as the lipid substrate, optimal
      activity was at 0.7 mM. The K(m) for myo-inositol was determined to be 0.55 mM.
      The optimal temperature for the PI synthase reaction was 55 degrees C. The C.
      albicans PI synthase shows differences to the Saccharomyces cerevisiae enzyme,
      such as activation by bivalent cations, inhibition by nucleotides, temperature
      optimum and activation energy, but also to the human PI synthase in preference
      for the lipid substrates, inhibition by nucleoside monophosphates and
      stabilization by Mn2+ and phospholipids.

PMID- 8740419
TI  - The hsp150 delta-carrier confers secretion competence to the rat nerve growth
      factor receptor ectodomain in Saccharomyces cerevisiae.
AB  - When the extracellular domain of rat low-affinity nerve growth factor receptor
      (NGFRe) was synthesized in Saccharomyces cerevisiae with the signal peptide of
      invertase, NGFRe was translocated to the endoplasmic reticulum (ER) and retained
      there. However, when NGFRe was fused to the C-terminus of the hsp150 delta
      carrier, the hsp150 delta-NGFRe fusion protein was efficiently secreted to the
      growth medium with no apparent retention in the ER. The NGFRe portion was
      disulphide-bonded and its single N-glycosylation site was occupied. The hsp150
      delta-carrier is an N-terminal signal peptide-containing fragment of a yeast
      secretory glycoprotein. Hsp150 delta-NGFRe, harvested from the culture medium,
      inhibited the cross-linking of [125I]NGF to authentic NGFR on the surface of
      human melanoma cells. Moreover, [125I]NGF could be chemically cross-linked to
      secretory hsp150 delta-NGFRe, suggesting that the NGFRe portion had adopted a
      ligand-binding conformation. However, inhibition of the cross-linking by
      unlabelled NGF was less effective than in the case of the authentic receptor. The
      hsp150 delta-carrier may have potential in the production of mammalian proteins,
      which require elaborate folding and disulphide formation in the ER.

PMID- 8740420
TI  - Factors affecting the mitotic stability of high-copy-number integration into the
      ribosomal DNA of Saccharomyces cerevisiae.
AB  - Yeast vectors suitable for high-level expression of heterologous proteins should
      combine a high copy number with high mitotic stability. The pMIRY integrative
      vector system, based upon targeted integration into the yeast rDNA locus,
      developed in our laboratory satisfies these criteria. However, insertion of a
      (foreign) gene drastically reduced its mitotic stability of the resulting vector
      in comparison to its parent. In this paper we have investigated a number of
      possible reasons for this reduction in stability. The results demonstrate that
      plasmid size is an important, but not the only, determinant of mitotic stability.
      Stable maintenance is only observed when the complete plasmid has a size no
      larger than that of the rDNA unit (9.1 kb). In addition stability depends upon
      the nature of the rDNA fragment present in the plasmid, required for targeting
      its integration. On the other hand, it turned out to be irrelevant for mitotic
      stability whether the heterologous gene was expressed or not. These findings will
      be important in the design of a pMIRY vector suitable for industrial production
      of heterologous proteins.

PMID- 8740421
TI  - Sequence of ptb1, a gene for the beta subunit of the type-II
      geranylgeranyltransferase from the fission yeast Schizosaccharomyces pombe.
AB  - We have isolated and sequenced the ptb1 gene from the fission yeast
      Schizosaccharomyces pombe. Sequence analysis suggests that Ptb1 is the beta
      subunit of the type-II geranylgeranyltransferase that is responsible for
      geranylgeranylation of the Rab-like YPT proteins in this yeast.

PMID- 8740422
TI  - The sequence of a 17,933 bp segment of Saccharomyces cerevisiae chromosome XIV
      contains the RHO2, TOP2, MKT1 and END3 genes and five new open reading frames.
AB  - We report the DNA sequence of a 17,933 bp fragment from the left arm of
      chromosome XIV of Saccharomyces cerevisiae. Analysis of the sequence reveals the
      presence of ten open reading frames (ORFs) larger than 100 codons. Four of these
      were previously identified as genes RHO2, TOP2, MKT1 and END3. Additionally, the
      NH2 end coding region of PMS1 is found in the 3' end of the sequence. No
      significant homology to any known protein has been found for the other five ORFs.

PMID- 8740423
TI  - The sequence of 12.8 kb from the left arm of chromosome XIV reveals a sigma
      element, a pro-tRNA and six complete open reading frames, one of which encodes a
      protein similar to the human leukotriene A4 hydrolase.
AB  - We have determined the nucleotide sequence of a 12.8 kb fragment from the left
      arm of chromosome XIV carried by the cosmid 14-16d. An analysis of the sequence
      reveals the presence of a sigma element, a pro-tRNA gene and eight open reading
      frames, six of which are complete. All of the eight open reading frames
      correspond to new genes. Of the eight new genes, two show strong similarities to
      a pair of new genes from chromosome IX, suggesting an ancestral duplication, and
      one gene encodes a protein similar to mammalian leukotriene A4 hydrolase.

PMID- 8740424
TI  - Molecular cloning of a third chitinase gene (CHT1) from Candida albicans.
AB  - Here we report the complete nucleotide sequence of a third chitinase gene (CHT1)
      from the dimorphic human pathogen Candida albicans. The deduced amino acid (aa)
      sequence of Cht1 consists of 416 aa and displays 36% protein sequence similarity
      to chitinases Cht2 and Cht3, from C. albicans. Interestingly the domain structure
      of Cht1 is truncated when compared to the other chitinases of C. albicans and
      lacks a Ser/Thr-rich region.

PMID- 8740426
TI  - Current awareness on yeast.

PMID- 8740425
TI  - The sequence of a 24,152 bp segment from the left arm of chromosome XIV from
      Saccharomyces cerevisiae between the BNI1 and the POL2 genes.
AB  - In the framework of the European Union programme for sequencing the genome of
      Saccharomyces cerevisiae we have determined the nucleotide sequence of a region
      of 24,152 bp located on the left arm of chromosome XIV between the BNI1 and the
      POL2 genes. The sequence was obtained by directed sequence analysis using a
      mixture of ExoIII and primer walking strategies. Subsequent analysis revealed 13
      open reading frames (ORFs) including four small ORFs completely internal to, or
      partly overlapping with, other ORFs. Five of these ORFs have been described
      previously (BNI1, APL1, LYP1, PIK1, POL2) and thus 74.8% of the 24,152 bp were
      already present in the databases prior to this sequencing effort. Interestingly,
      all 13 identified ORFs are characterized by a low codon adaptation index (0.04
      0.22). In addition, this region of chromosome XIV shows an unusually high gene
      density with about 88% of coding DNA. This amounts to one gene per 2177 bp, which
      is significantly above the average gene length (about 1500 bp). For eight ORFs
      considerable homologies to 'Expressed Sequence Tags' derived from human cDNAs
      located in the XREF database could be identified.

PMID- 8740427
TI  - Vinculin, talin and focal adhesions.

PMID- 8740428
TI  - A myosin family reunion.

PMID- 8740429
TI  - Titin expression as an early indication of heart and skeletal muscle
      differentiation in vitro. Developmental re-organisation in relation to
      cytoskeletal constituents.
AB  - Established myogenic cell lines of different species and tissue origin have been
      used to study expression and organisation of muscle-specific proteins during
      differentiation. Furthermore, primary cultures of rat myocard cells were used to
      examine these same processes during dedifferentiation. In particular, we were
      interested in the general mechanism that underlies the changes in the
      supramolecular organisation of titin during in vitro myogenesis. It became
      obvious that in the differentiating muscle cell cultures the redistribution of
      desmin, actin and myosin in a typical, differentiation state dependent fashion,
      always showed a certain delay when compared to titin. The sequence of changes in
      the assembly of cytoskeletal and sarcomeric structures observed during
      differentiation of the cell lines was reversed during the process of
      dedifferentiation in cultured rat myocard cells. These results all indicate that
      titin is an early marker of myogenic differentiation, both in vivo and in vitro,
      and the typical reorganisation of this giant molecule is independent of species
      or muscle cell type.

PMID- 8740430
TI  - Lack of myoblasts migration between transplanted and host muscles of mdx and
      normal mice.
AB  - Extensor digitorum longus muscles of normal mice (C57BL/10ScSn hereafter called
      C57) were orthotopically transplanted into dystrophin-deficient mice (mdx) and
      reciprocally, mdx Extensor digitorum longus muscles were transplanted into C57
      mice. After an initial phase of degeneration, transplanted muscles regenerate
      nearly completely, as evaluated from the maximum isometric force of muscles
      isolated 60 days after the surgery. In other similar experiments, instead of
      isolating the grafted muscles, we excised the antero-external muscles of the leg,
      including the grafted muscle. Cryostat cross-sections at three levels along the
      muscles were immunostained with an anti-dystrophin antibody. No muscle cells of
      dystrophin-deficient muscles grafted into normal mice took the antibody except a
      few 'revertant' fibres, while all the muscle cells of the normal host were
      immunostained. Reciprocally, all the muscles cells of normal grafts were stained,
      whilst no antibody stained the cells of the surrounding muscles of the dystrophin
      deficient host. These experiments show that very few if any of the myoblasts or
      muscle precursor cells, active during the regeneration of grafted muscle, migrate
      into the adjacent muscles. These results could be explained by the absence, in
      our work, of injuries of the grafted and adjacent host muscles epimysium and the
      absence of extensive inflammatory reactions. This lack of myoblast mobility
      suggest that when myoblast transfer is applied to muscle therapy, it will be
      necessary to inject myoblasts within each muscle to obtain an efficient
      treatment.

PMID- 8740431
TI  - Simulation of the rapid regeneration of the actin-myosin working stroke with a
      tight coupling model of muscle contraction.
AB  - A. F. Huxley's suggestion in Nature (1992) that a structural modification in the
      myosin head driven by phosphate release can explain the rapid regeneration of the
      working stroke, which follows the quick recovery elicited by a step release of
      moderate size (3-6 nm per half-sarcomere), has been tested with a theoretical
      model. It is assumed that, in the shortening muscle, cross-bridges can undergo
      their work producing interaction in two ways distinct for the biochemical state
      and for the amount of filament sliding allowed. During shortening at low speed,
      as well as after a shortening step of moderate size, phosphate release from the
      cross-bridge in the AM-ADP-P state promotes a 100 s-1 structural change which
      resets the myosin head in a configuration that allows for a new complete working
      stroke in the AM-ADP state. In this case the total sliding distance for
      interaction is about 15 nm. With the increase in shortening velocity a
      progressively larger fraction of interacting cross-bridges remains in the AM-ADP
      P state throughout the working stroke and the sliding distance for interaction is
      about 11 nm. Reattachment of detached cross-bridges occurs at moderate rate
      whichever is the pathway from which they originate. The model predicts
      satisfactorily the time course of the rapid regeneration of the working stroke in
      double step experiments, but fails to simulate the transition to the steady state
      response in staircase experiments, the maximum power output during steady
      shortening and the decrease in rate of energy liberation at high shortening
      velocities. These results strengthen the conclusion of our previous modelling
      work where we demonstrated that the condition necessary to fit the mechanical and
      energetic properties of shortening muscle is to assume two pathways for cross
      bridge cycling distinct for the kinetics of detachment and reattachment.

PMID- 8740432
TI  - The effect of 2,5-di-(tert-butyl)-1,4-hydroquinone on force responses and the
      contractile apparatus in mechanically skinned muscle fibres of the rat and toad.
AB  - In this study, we investigated the effect of the Ca2+ pump inhibitor, 2,5-di
      (tert-butyl)-1,4-hydroquinone on the function of the contractile apparatus, Ca2+
      uptake, the permeability of the sarcoplasmic reticulum to Ca2+ and excitation
      contraction coupling, in mechanically skinned muscle fibres of the rat and toad.
      2,5-di-(tert-butyl)-1,4-hydroquinone had no significant effect on the maximum
      force and Ca2+ sensitivity of the contractile apparatus in rat and toad fibres at
      concentrations of 20 and 5 microM respectively. In rat fibres, 2,5-di-(tert
      butyl)-1,4-hydroquinone was found to inhibit sarcoplasmic reticulum Ca2+ loading
      in a dose dependent manner, with a half maximal effect at 2 microM. In toad
      fibres, 5 microM 2,5-di-(tert-butyl)-1,4-hydroquinone completely blocked
      sarcoplasmic reticulum Ca2+ loading. Exposure to 5 mM BAPTA revealed a small
      resting sarcoplasmic reticulum Ca2+ leak in unstimulated rat fibres. This Ca2+
      leak was not significantly affected by the presence of 20 microM 2,5-di-(tert
      butyl)-1,4-hydroquinone, suggesting that 2,5-di-(tert-butyl)-1,4-hydroquinone
      does not substantially block or activate the sarcoplasmic reticulum Ca2+ release
      channels. Depolarisation-induced force responses elicited in rat and toad skinned
      fibres were not significantly affected by 0.5 microM 2,5-di-(tert-butyl)-1, 4
      hydroquinone. In the rat fibres, 5 and 20 microM 2,5-di-(tert-butyl)-1,4
      hydroquinone greatly increased the peak and duration of initial depolarisation
      induced force responses, while subsequent responses were reduced. 2,5-di-(tert
      butyl)-1,4-hydroquinone did not affect excitation contraction coupling, as
      depolarisation-induced force responses similar to initial controls could be
      elicited after 2,5-di-(tert-butyl)-1,4-hydroquinone exposure, provided that the
      initial Ca2+ release in 2,5-di-(tert-butyl)-1,4-hydroquinone was chelated with
      0.5 mM EGTA (to prevent Ca(2+)-dependent damage) and the sarcoplasmic reticulum
      was reloaded with Ca2+. In the toad fibres, 5 microM 2,5-di-(tert-butyl)-1, 4
      hydroquinone had a similar effect on depolarisation-induced force responses to
      that observed at 20 microM 2,5-di-(tert-butyl)-1, 4-hydroquinone in rat fibres.
      This study shows that 2,5-di-(tert-butyl)-1,4-hydroquinone specifically and
      reversibly inhibits the sarcoplasmic reticulum Ca2+ pump in skeletal muscle and
      therefore, 2,5-di-(tert-butyl)-1,4-hydroquinone could be a valuable tool for
      investigating the role of the sarcoplasmic reticulum in Ca2+ homeostasis in
      skeletal muscle.

PMID- 8740433
TI  - Cloning of the cDNA encoding rat myosin heavy chain-A and evidence for the
      absence of myosin heavy chain-B in cultured rat mast (RBL-2H3) cells.
AB  - The complete amino acid sequence (1961 amino acids) of a vertebrate cellular
      myosin heavy chain-A was deduced from cDNA clones of a secretory rat mast cell
      line, the RBL-2H3 cell. The rat, human and chicken cellular myosin heavy chain-A
      exhibited high similarity in domains that allow binding of ATP and actin. The
      amino acid sequence of non-muscle myosin heavy chain-A from rat was 96% identical
      to that in human and 92% identical to that in chicken. Northern blot analysis of
      mRNA indicated the presence of single message of 7.4 kilobases. Northern blot,
      reverse-transcriptase polymerase chain reaction, and Western blot with isoform
      specific antibodies indicated that RBL-2H3 cells expressed exclusively myosin
      heavy chain-A. Unlike rat PC12 cells, as well as a wide variety of other cultured
      cells and tissues, myosin heavy chain-B mRNA and protein were not detectable in
      RBL-2H3 cells. Because RBL-2H3 cells can be stimulated to release secretory
      granules as well as newly generated arachidonic acid and cytokines but lack
      myosin heavy chain-B, this cell line may provide a unique model to study the role
      of myosin heavy chain-A in cellular responses to antigen and other stimulants.

PMID- 8740434
TI  - Cloning of a phospholipase C-delta 1 of rabbit skeletal muscle.
AB  - The phospholipase C isoform responsible for the increase in the total myoplasmic
      inositol 1,4,5-trisphosphate concentration during tetanic contraction of isolated
      skeletal muscle and its mechanism of activation is not known. We have cloned and
      sequenced a phospholipase C cDNA of rabbit skeletal muscle coding for a protein
      of 745 amino acids with a molecular mass of 84,440 kDa. The deduced amino acid
      sequence exhibits the phospholipase C-specific domains X and Y which according to
      current knowledge very likely represent the catalytic centre of the enzyme. An
      overall sequence homology of 88% to the phospholipase C-delta 1 of rat brain
      suggests that the encoded protein represents a phospholipase C-delta 1 isoform of
      rabbit skeletal muscle. Northern blot analysis shows, that this phospholipase C
      delta is dominantly expressed in skeletal muscle, less strongly in smooth muscle
      (uterus) and lung and weakly in heart, kidney and brain. In the N-terminal part
      of the primary structure a consensus sequence for a canonical EF-hand Ca2+
      binding domain can be identified together with a short positively charged motif
      which recently has been suggested to be essential for the binding of
      phosphatidylinositol 4,5-bisphosphate. If these two domains which are unique for
      phospholipase C-delta are sufficient in establishing a mechanism for the
      activation of the enzyme, inositol 1,4,5-trisphosphate formation in skeletal
      muscle could be the consequence of an increase in myoplasmic Ca2+.

PMID- 8740435
TI  - Cytochemical localization of Ca(2+)-ATPases and demonstration of ATP-dependent
      calcium sequestration in giant smooth muscle fibres of Beroe.
AB  - A cytochemical analysis of the mechanisms underlying cytosolic calcium regulation
      was undertaken in the giant smooth muscle fibres of the marine invertebrate
      Beroe. The ability of the sarcoplasmic reticulum to accumulate Ca2+ was
      demonstrated on living skinned single cells. In the presence of oxalate, and
      physiological concentrations of Ca2+, calcium oxalate crystals were formed in the
      lumen of tubules and cisternae of the sarcoplasmic reticulum. The subcellular
      distribution of Ca(2+)-ATPase was studied with a cytochemical technique; a dense
      precipitate resulting from Ca(2+)-ATPase activity was found on the plasma
      membrane, on the membranes of tubules and cisternae of the sarcoplasmic
      reticulum, and in mitochondria.

PMID- 8740436
TI  - Trace element food toxicology: an old and ever-growing discipline.
AB  - Food toxicology (FT) is an old science whose origins may go back to primitive
      humans. However, due to major environmental damage, daily market launches of new
      food products, and the analytical ability to detect ever small quantities of
      toxicants in foods, FT is also an ever-growing science with an enormous task
      ahead. With respect to trace elements, current research trends can be encompassed
      under the headings of detection, control, and toxicological evaluation. Under the
      heading detection, quality, sensitivity, speed, automation, and specificity for
      each food type are the characteristics currently sought when developing new
      methodologies. Under control, there is a great need for constant monitoring, on
      an international level, of the levels of trace elements present in foods; and for
      development and application of new methodologies to guarantee product and process
      safety. Under toxicological evaluation, information about the bioavailability of
      trace elements and consequently studies of the chemical species present in foods
      have top priority. The work still outstanding in the study of trace element FT is
      immense, because it is necessary to achieve a profound understanding of the
      toxicological characteristics of food products in relation to trace elements; to
      give information to food manufacturers that they can use to adapt their
      production so that it meets the requirements of international legislation and
      demands for quality and innocuousness on the part of the market and consumers;
      and to develop standards regulating the maximum content of trace elements,
      according to the content of the various species.

PMID- 8740437
TI  - Exercise and cancer: linkages with obesity?
AB  - This review examines possible protection against various types of tumors from
      both occupational and leisure-time physical activity. A growing number of well
      controlled studies suggest that both hard physical work and an active leisure
      reduce the overall incidence of cancer. Benefit is demonstrated most clearly for
      colonic tumors; here, benefit persists after control of the data for body mass
      index, and a likely mechanism is the speeding of colonic transit, with a
      resulting decrease in exposure to carcinogens. There are occasional reports of
      protection against tumors of the breast, reproductive tract, and other body
      organs. In some of these latter sites, potential mechanisms of protection include
      a suppression of sex hormone secretion and reduction of body fat depots, where
      androgens are converted to toxic estrogen derivatives. While vigorous athletic
      participation may well modulate hormone output, a reduction of body fat is a more
      likely explanation of any benefit from more moderate physical activity.
      Protection against cancer is unlikely to become a major argument for an active
      lifestyle, but it is nevertheless a useful byproduct of physical activity
      undertaken with other health objectives.

PMID- 8740438
TI  - Oxidatively modified LDL and atherosclerosis: an evolving plausible scenario.
AB  - Much evidence has accumulated that implicates the oxidative modification of low
      density lipoprotein (LDL) in the early stages of atherogenesis. The antioxidant
      nutrients alpha-tocopherol, ascorbic acid, and betacarotene have been shown to
      inhibit in vitro LDL oxidation. In addition, they have been shown to increase the
      resistance of LDL to oxidation when given to animals and humans. Because plasma
      levels of these nutrients can be increased by dietary supplementation with
      minimal side effects, they may show promise in the prevention of coronary artery
      disease.

PMID- 8740439
TI  - Applications of magnetic resonance imaging in food science.
AB  - The physical and chemical changes that occur in foods during growth, harvest,
      processing, storage, preparation, and consumption are often very difficult to
      measure and quantify. Magnetic resonance imaging (MRI) is a pioneering
      technology, originally developed in the medical field, that is now being used in
      a large number of disciplines to study a wide variety of materials and processes.
      In food science, MRI techniques allow the interior of foods to be imaged
      noninvasively and nondestructively. These images can then be quantified to yield
      information about several processes and material properties, such as mass and
      heat transfer, fat and ice crystallization, gelation, water mobidity, composition
      and volume changes, food stability and maturation, flow behavior, and
      temperature. This article introduces the fundamental principles of MRI, presents
      some of the recent advances in MRI technology, and reviews some of the current
      applications of MRI in food science research.

PMID- 8740440
TI  - CaM kinase II in long-term potentiation.
AB  - The observation that autophosphorylation converts CaM kinase II from the Ca(2+)
      dependent form to the Ca(2+)-independent form has led to speculation that the
      formation of the Ca(2+)-independent form of the enzyme could encode frequency of
      synaptic usage and serve as a molecular explanation of "memory". In cultured rat
      hippocampal neurons, glutamate elevated the Ca(2+)-independent activity of CaM
      kinase II through autophosphorylation, and this response was blocked by an NMDA
      receptor antagonist, D-2-amino-5-phosphonopentanoate (AP5). In addition, we
      confirmed that high, but not low frequency stimulation, applied to two groups of
      CA1 afferents in the rat hippocampus, resulted in LTP induction with concomitant
      long-lasting increases in Ca(2+)-independent and total activities of CaM kinase
      II. In experiments with 32P-labeled hippocampal slices, the LTP induction in the
      CA1 region was associated with increases in autophosphorylation of both alpha and
      beta subunits of CaM kinase II 1 h after LTP induction. Significant increases in
      phosphorylation of endogenous CaM kinase II substrates, synapsin I and
      microtubule-associated protein 2 (MAP2), which are originally located in
      presynaptic and postsynaptic regions, respectively, were also observed in the
      same slice. All these changes were prevented when high frequency stimulation was
      applied in the presence of AP5 or a calmodulin antagonist, calmidazolium.
      Furthermore, in vitro phosphorylation of the AMPA receptor by CaM kinase II was
      reported in the postsynaptic density and infusion of the constitutively active
      CaM kinase II into the hippocampal neurons enhanced kainate-induced response.
      These results support the idea that CaM kinase II contributes to the induction of
      hippocampal LTP in both postsynaptic and presynaptic regions through
      phosphorylation of target proteins such as the AMPA receptor, MAP2 and synapsin
      I.

PMID- 8740441
TI  - Modulation of glutamate receptors by calcium/calmodulin-dependent protein kinase
      II.

PMID- 8740442
TI  - Specificity of cysteine sulfinate decarboxylase (CSD) for sulfur-containing amino
      acids.
AB  - Cysteine sulfinate decarboxylase (CSD) which decarboxylates cysteine sulfinic
      acid (CSA) to form hypotaurine is thought to be involved in the biosynthesis of
      taurine. It was recently localized in astrocytes in the cerebellum and
      hippocampus by immunocytochemistry. Another sulfur-containing amino-acid (SCAA),
      homocysteic acid (HCA), was also found in astrocytes in these regions. We
      therefore investigated the specificity of CSD vs CSA and HCA as well as the
      related analogs homocysteine sulfinic acid (HCSA) and cysteic acid (CA). CSD was
      immunotrapped from brain and liver tissue supernatant using a specific CSD
      antiserum and Protein-A Sepharose. It was then incubated with the L-form of the
      various SCAA. Reaction products were identified and quantified by pre-column o
      phthalaldehyde derivatization HPLC. CA and HCA from 2.5 to 25 mM inhibited the
      formation of hypotaurine from CSA (0.25 mM). Moreover, the inhibition curves were
      parallel for liver and brain CSD. CA or HCA (25 mM) elicited a near-total
      inhibition. HCSA did not produce a significant inhibition up to 25 mM. Incubation
      with 25 mM CSA or CA led to the formation of hypotaurine and taurine,
      respectively. The ratio of formation of taurine to that of hypotaurine was
      similar for CSD from liver and brain. In contrast no homotaurine, the
      decarboxylated reaction product of HCA, could be detected following incubation
      with 25 mM HCA. According to the sensitivity of the HPLC analysis this indicates
      that the decarboxylation of HCA, if any, was 130-fold and 50-fold less than that
      of CSA by CSD from liver and brain, respectively, in our experimental conditions.
      Similarly, following incubation with HCSA, no new peak appeared on the
      chromatogram when compared to a blank sample. These results show that CSD from
      either brain or liver has a high specificity for CSA and CA, which are the SCAA
      involved in the biosynthesis of taurine. HCA is an inhibitor of CSD but does not
      appear to be a substrate for CSD in vitro. HCSA is neither a substrate nor an
      inhibitor of CSD in vitro. Accordingly, CSD is unlikely to play a role in the
      metabolism of HCA or HCSA in vivo.

PMID- 8740443
TI  - Characterization and tissue distribution of opioid-binding cell adhesion molecule
      (OBCAM) using monoclonal antibodies.
AB  - Monoclonal antibodies to opioid-binding cell adhesion molecule (OBCAM) were
      produced against a synthetic OBCAM peptide. Immunoblotting analysis revealed that
      the antibodies reacted with 58 and/or 51 kDa proteins in P2 membranes from
      bovine, rat, mouse, guinea pig and rabbit brains. In bovine brain, the 58 and 51
      kDa proteins were present in the striatum and cerebral cortex at high levels, but
      not in the pituitary. OBCAM was also detected in the cerebellum mainly in the 51
      kDa form. In other tissues, the proteins were found in the spleen at very low
      levels, but not at all in the liver or kidney of the rat. OBCAM was effectively
      solubilized from bovine P2 membranes by bacterial phosphatidylinositol specific
      phospholipase C (PI-PLC), indicating that OBCAM is a glycosylphosphatidylinositol
      (GPI)-anchored protein. PI-PLC treatment, however, had little effect on the
      opioid binding activity of the residual P2 membranes. The molecular weight of the
      proteins (58 and 51 kDa) was reduced to 36 kDa following treatment with N
      glycanase but not further reduced after subsequent treatment with neuraminidase
      and O-glycanase, suggesting that OBCAM has N-glycosylated carbohydrate chains and
      that its two isoforms are different, at least, in the degree of N-glycosylation.
      Taken together, these results suggest that OBCAM consists of 58/51 kDa GPI
      anchored glycoproteins which are highly N-glycosylated and are expressed mainly
      in the nervous system.

PMID- 8740444
TI  - Thyrotropin-like immunoreactivity in human retina: immunoreactive co-localization
      in ganglion cells and perivascular fibers.
AB  - The present immunocytochemical study has demonstrated immunoreactive thyrotropin
      like ganglion cell populations as well as perivascular fibers in the human retina
      by using specific antiserum. Thyrotropin is a pituitary glycopeptide involved in
      the synthesis and release of thyroid hormones. The existence and functions of
      peptides in vertebrate retinas are still not well known. Many authors have
      reported neuropeptide immunoreactivity in the human retina which have had their
      functions established in the neuroregulatory processes of vision. Moreover, some
      authors have reported the possibility that the fiber terminal of peptidergic
      neurons may also be a blood vessel. The appearance of immunoreactive-cells in
      human retina, e.g. existence of retinal ganglion cells with thyrotropin-like
      immunoreactivity, indicates the existence of specific mechanisms that would be
      mediated by these peptides which are located near immunoreactive ganglion cells.
      We hypothesize that there is an intrinsic mechanism for blood flow control,
      mediated by retinal ganglion cells which may regulate vessel diameter according
      to its luminous stimuli. No-one has demonstrated the presence or the functional
      existence of thyrotropin-like immunoreactive structures in the vertebrate retina,
      or on the side of the pituitary-thyroid axis. To the best of our knowledge this
      is the first time that thyrotropin has been immunocytochemically demonstrated in
      the human retina. Thus, we suggest that thyrotropin acts as a neuromodulator in
      the human retina, which is implicated in blood flow control.

PMID- 8740445
TI  - Inhibition of sodium-dependent uptake processes in purified rat brain
      synaptosomes by Lophozozymus pictor toxin and palytoxin.
AB  - To get an insight into the mechanism of neurotoxicity exhibited by Lophozozymus
      pictor toxin (LPTX) and the toxin isolated from P.caribaeorum (C-PTX) studies
      were carried out on the effect of these toxins on the uptake of selected
      substrates (neurotransmitters, amino acids and glucose) in isolated nerve
      endings. The toxins were found to inhibit the uptake of gamma-aminobutyric acid
      (GABA), noradrenaline, choline, L-leucine and 2-deoxy-D-glucose in rat brain
      synaptosomes. LPTX- or C-PTX-induced inhibition of synaptosomal uptake was
      reduced in the absence of Na+ in the assay medium. Synaptosomes exposed to LPTX
      and C-PTX release K+ in a dose-dependent manner. Ouabain, a selective inhibitor
      of the plasma membrane Na+, K(+)-ATPase could inhibit LPTX- and C-PTX-induced K+
      efflux from synaptosomes and alleviate the toxin-induced inhibition of
      synaptosomal GABA uptake. It appears that the induction of ionic flux is the
      primary cause of toxicity by these toxins leading to the inhibition of Na(+)
      dependent uptake processes in synaptosomes. The antagonistic action of ouabain
      suggests the involvement of the membrane sodium pump in the development of
      cytotoxicity.

PMID- 8740446
TI  - Changes in cholecystokinin mRNA expression in methamphetamine-induced behavioral
      sensitization.
AB  - Neuropeptide cholecystokinin (CCK) mRNA was measured in the rat brain
      subchronically treated with methamphetamine (MAP). Male Wistar rats were injected
      daily with MAP (3 or 6 mg/kg, i.p., once a day) or saline for 14 days.
      Progressive reinforcement was observed in MAP-induced stereotyped behaviors.
      After 7 or 14 days of discontinuation, the rats were decapitated and the brains
      were prepared for Northern blot analysis using 32P-labeled cDNA probes. Northern
      blot analysis revealed that the levels of CCK mRNA in the frontal cortex and the
      hippocampus of 3 or 6 mg/kg MAP-treated rats were significantly decreased,
      compared to the saline-treated controls. These findings indicate that the
      alteration in CCK mRNA levels in the frontal cortex and the hippocampus of MAP
      treated rats persisted for at least 2 weeks and might be involved in the
      expression of MAP-induced long-lasting behavioral sensitization (reverse
      tolerance).

PMID- 8740447
TI  - ATP induces release of newly synthesized dopamine in the rat striatum.

PMID- 8740448
TI  - Ca2+ and H+ antagonize the decrease of [3H]MK-801 binding induced by glutamate
      and glycine in the presence of Mg2+.
AB  - We have studied the effects of various cations on [3H]MK-801 binding to N-methyl
      D-aspartate (NMDA) receptors in membrane preparations of the rat cerebral cortex.
      Low concentrations of Tris, K+, Na+, Mg2+, and Ca2+ enhanced submaximally
      stimulated [3H]MK-801 binding. At high concentrations, all compounds inhibited
      [3H]MK-801 binding, possibly by a direct competitive effect. H+ decreased the
      observed association rate of [3H]MK-801 binding observed as a decreased [3H]MK
      801 binding under nonequilibrium conditions, apparently by decreasing the
      sensitivity of the glutamate and glycine effects on the association rate. In
      addition, Tris, Na+, Mg2+, and possibly K+ at very high concentrations, permitted
      glutamate and glycine to decrease [3H]MK-801 binding, probably reflecting a
      decreased affinity of [3H]MK-801 binding. In contrast, Ca2+ and H+ antagonized
      these glutamate- and glycine-induced decreases of [3H]MK-801 binding observed in
      the presence of Mg2+, possibly by a direct competitive action on the permissive
      Mg2+ effect. These Ca2+ and H(+)-induced increases in [3H]MK-801 binding in the
      presence of Mg2+ may correspond to an increase in the potency of the Mg2+ block.

PMID- 8740449
TI  - Effect of serotonin and neuropeptides on adenylate cyclase of the central nervous
      system and peripheral organs of the freshwater snail Planorbarius corneus.
AB  - The effect of serotonin, FMRFamide and the small cardioactive peptide B (SCPB) on
      adenylate cyclase activity of the central nervous system and some peripheral
      organs of the freshwater snail Planorbarius corneus was investigated. The amine
      and the cardioactive peptide stimulated the enzyme, although with different
      potencies, in all tissues studied and, when tested in combination, an additive
      activation was obtained. FMRFamide induced differential effects in the various
      targets: marked stimulation of adenylate cyclase, additive to that provoked by
      serotonin or SCPB, in salivary glands; inhibition of the enzyme, both alone and
      in combination with the other neuromediators, in the nervous tissue; whereas no
      influence was found in adenylate cyclase activity in the buccal mass. In the last
      of these tissues, the peptide might act through an intracellular second messenger
      other than cyclic AMP. The responsiveness of adenylate cyclase to these
      neuromediators in all the central ganglia suggested that they can exert an
      important role as neurotransmitters and/or neuromodulators in the central nervous
      system of the snail. Moreover, in the light of the differential sensitivity of
      adenylate cyclase in the salivary glands and buccal mass, we suggest that
      serotonin, FMRFamide and SCPB modulate the feeding behaviour of P. corneus in a
      complex way.

PMID- 8740450
TI  - Recruitment of peripheral-type benzodiazepine receptors after acute stress in
      chick forebrain membranes: action of Triton X-100.
AB  - A significant increase in the number of measurable [3H]Ro 5-4864 receptors was
      found in forebrain membranes of chicks submitted to 15 min of acute swim stress
      compared to non-stressed chicks. In addition, low subsolubilizing concentrations
      of Triton X-100 caused a significant increase in the measurable [3H]Ro 5-4864
      receptor number in forebrain membranes from non-stressed chicks. However, this
      increase caused by Triton X-100 was not observed when tested in forebrain
      membranes from stressed chicks. In all cases the affinity remained unchanged.
      These results suggest that: (1) acute stress and Triton X-100 induce receptor
      increase by enhancing [3H]Ro 5-4864 accessibility to a pool of receptors not
      detected before stress or in the absence of detergent; (2) the pool of non
      measured receptors represents about a third of the total in control chicks; (3)
      the increments are not additive and could involve receptors coming from the same
      non-measured pool; (4) the receptor increase during a short time of stress could
      be explained by recruitment of receptors but not by an increase in the receptor
      protein biosynthesis; (5) stress induces a maximal recruitment of measurable [
      3H]Ro 5-4864 receptors.

PMID- 8740451
TI  - A developmental study of protein phosphorylating systems stimulated by phorbol
      dibutyrate in micro-slices of rat brain.
AB  - Age-dependent changes in the activity of protein phosphorylating systems
      stimulated by phorbol dibutyrate (M(r) range 40-80 kDa) were studied in micro
      slices from rat brain labelled with [32P]orthophosphate. In adult animals phorbol
      stimulated the phosphorylation of the known substrates of protein kinase C (B
      50/GAP-43 and MARCKS) and 3 unknown polypeptides: a basic molecule of 74 kDa
      (pp74B) and acidic molecules of 60 kDa (pp60A) and 42 kDa (pp42C). In neonatal
      animals the labelling of MARCKS was relatively very high as previously reported.
      Labelling of pp60A was present at birth, but increased during development;
      labelling of pp74B was only detected after days 8-10. The activity of the system
      labelling pp42C was very high during the first 2 weeks postnatal and then
      declined rapidly. The labelling of pp74B was considerably higher in slices from
      the cerebral cortex compared with the hippocampus; no regional differences in the
      labelling of pp60A were observed. Compared to B-50/GAP-43 and MARCKS, stimulation
      of phosphorylation of pp74B and pp60A required a higher concentration of phorbol.
      The substrates of all the phorbol-responsive systems, with the exception of
      pp74B, were soluble in 40% acetic acid. The possible identity of pp60A, pp74B and
      pp42C is discussed.

PMID- 8740452
TI  - Activation of serotonergic 5-HT1A receptor reduces Ca(2+)- and glutamatergic
      receptor-evoked arachidonic acid and No/cGMP release in adult hippocampus.
AB  - Stimulation of glutamatergic NMDA receptor in adult rat hippocampal
      synaptoneurosomes induces statistically significant Ca(2+)-dependent liberation
      of arachidonic acid (AA) and nitric oxide (NO)-activated cGMP synthesis. NMDA
      acting for 5 min at 100 microM markedly increases, by approx. 25%, Ca(2+)
      mediated AA release from phospholipids of hippocampal synaptoneurosomes.
      Prolonged stimulation of NMDA receptor up to 10 min has smaller stimulatory
      effect and enhances AA release by about 6%. Moreover, NMDA activates NO-dependent
      cGMP production by approx. 5 times more than the Ca2+ itself. Release of both
      these second messengers is completely blocked by the competitive NMDA antagonist,
      APV (100 microM). The NMDA-mediated cGMP elevation completely depends on NO
      action, and is abolished by the specific inhibitor of NO synthase, NG-nitro-L
      arginine. Moreover, serotonin at 10 microM in the presence of 10 microM
      pargyline, potently decreases both Ca(2+)- and NMDA receptor-mediated AA and cGMP
      release in hippocampal synaptoneurosomes. The agonist of 5-HT1A receptor,
      buspirone, in a way similar to serotonin itself, counteracts the Ca(2+)- and also
      NMDA receptor-evoked AA release and cGMP accumulation. An antagonist of 5-HT1A
      receptor, NAN-190, eliminates the effect of serotonin and buspirone on AA and
      NO/cGMP liberation. An antagonist of serotonergic 5-HT2 receptor, ketanserin, has
      no effect on the Ca2+ and serotonin action. These results indicate that
      serotonin, through 5-HT1A receptor, potently antagonizes the action of excitatory
      amino acid for AA release and NO/cGMP synthesis in the adult rat hippocampus. In
      conclusion, the interaction of serotonin with the glutamatergic system in the
      hippocampus may play an important role in the modulation of a signal transduction
      pathway, and by this molecular mechanism serotonin may exert a neuroprotective
      effect on hippocampal neurons.

PMID- 8740453
TI  - The endogenous agonist quinolinic acid and the non endogenous homoquinolinic acid
      discriminate between NMDAR2 receptor subunits.
AB  - Quinolinic acid is an endogenous neurotoxin with NMDA receptor agonist
      properties. As such it may be the etiologic agent in many diseases. In this paper
      the NMDA receptor agonist properties of quinolinic acid, as well as those of
      homoquinolinic acid, a non endogenous analogue, were investigated in Xenopus
      oocytes injected with 12-day-old rat cortical mRNA or with recombinant NMDA
      receptors. In oocytes injected with cortical mRNA, quinolinic acid was a weak
      NMDA receptor agonist: millimolar concentrations were necessary to induce
      responses that were smaller than maximal responses induced by NMDA;
      homoquinolinic acid and NMDA had similar affinities but different efficacies:
      maximal responses induced by homoquinolinic acid were larger than maximal
      responses induced by NMDA. Cortical mRNA, as verified by RT-PCR and restriction
      analysis, contains various NMDA subunits. In order to investigate if the low
      affinity or efficacy of quinolinic acid could be explained by receptor
      composition, the pharmacological properties of the putative agonists were
      investigated in oocytes expressing binary combinations of recombinant NMDA
      receptors. Quinolinic acid did not activate receptors containing NR1 + NR2C but
      did activate receptors containing NR1 + NR2A and NR1 + NR2B even if only at
      millimolar concentrations; homoquinolinic acid activated all subunit combinations
      but was less efficient than NMDA only in the NR1 + NR2C subunit combination. The
      relative efficacies of quinolinic acid and homoquinolinic acid were evaluated by
      comparing the maximal responses induced by these agonists with those induced by
      NMDA and glutamate in the same oocytes. The rank order of potency was quinolinic
      acid < NMDA < homoquinolinic acid < or = glutamate for the NR1 + NR2A and NR1 +
      NR2B combinations whereas for NR1 + NR2C it was quinolinic acid << <<
      homoquinolinic acid < NMDA < or = glutamate. The use of quinolinic acid and
      homoquinolinic acid may thus help to identify endogenous receptors containing the
      NR2C subunit.

PMID- 8740454
TI  - Pemphigus: from immunofluorescence to molecular biology.
AB  - Since the discovery of autoantibodies in patients with pemphigus, pemphigus has
      been intensively studied by dermatologists and cutaneous or cellular biologists
      by means of various techniques including immunofluorescence, immunoelectron
      microscopy, immunoprecipitation, immunoblotting, and molecular biology. In this
      article, up-dated topics on pemphigus obtained by each individual technique are
      reviewed. In the course of immunofluorescence studies on unusual cases of
      blistering diseases, a new entity characterized by immunoglobulin A (IgA)-type
      autoantibodies directed against keratinocyte cell surfaces has been discovered.
      Immunoelectron microscopy using low temperature post-embedding gold labeling
      enabled us to quantitate binding sites of pemphigus autoantibodies within
      desmosomes at different levels of epidermis. Immunoprecipitation and immunoblot
      analyses allowed us to characterize antigen complexes in paraneoplastic
      pemphigus. Finally, approaches using molecular biology not only have given us a
      fundamental insight that pemphigus autoantigen is a cadherin-type cell adhesion
      molecule both in pemphigus vulgaris and pemphigus foliaceus, but also provided
      tools to develop novel diagnostic and therapeutic strategies.

PMID- 8740455
TI  - Studies of autoantigens recognized by IgA anti-keratinocyte cell surface
      antibodies.
AB  - We have examined autoantigens for IgA anti-keratinocyte cell surface antibodies
      in 17 intercellular IgA vesiculopustular dermatosis (IAVPD) cases showing only
      IgA antibodies and 5 cases showing both IgG and IgA antibodies (G A cases). IAVPD
      cases were divided into two subtypes: (1) intraepidermal neutrophilic IgA
      dermatosis type showing pustule formation throughout the epidermis and IgA
      antibodies reactive with the entire epidermis and (2) subcorneal pustular
      dermatosis type containing IgA antibodies reactive with the uppermost portion of
      the epidermis. Most G A cases showed atypical clinical features. With immunoblot
      analysis of normal human epidermal extracts, IgA antibodies in these cases showed
      no specific reactivity with either pemphigus foliaceus antigen (desmoglein 1) or
      pemphigus vulgaris antigen (desmoglein 3), except that IgC antibodies in one G/A
      case each recognized one of the two antigens. With immunoblotting of desmosome
      enriched fraction obtained from bovine snout epidermis, IgA antibodies in 10
      IAVPD and 3 G/A cases and IgG antibodies in 4 G/A cases showed reactivity with
      either desmoglein 1 or desmocollin another desmosomal cadherin. These results
      indicate that IAVPD and G/A cases are heterogeneous in terms of both clinical
      features and antigens and that the IgA autoantibodies in these cases may react
      with different antigens from those for IgG autoantibodies.

PMID- 8740456
TI  - The study of ultraviolet B-induced apoptosis in cultured mouse keratinocytes and
      in mouse skin.
AB  - The responsibility of ultraviolet B (UVB) radiation for the induction of
      apoptosis in epidermal cells in vitro and in vivo was examined. Using cultured
      mouse keratinocytes, PAM212 cells, the morphological development of apoptotic
      cells (AC) after UVB irradiation was observed, and their DNA status was also
      examined. In addition, histochemical analysis was performed to establish whether
      the UVB-mediated sunburn cells (SBC) were AC or not. The cultured cells exposed
      to UVB showed the morphological characteristics of AC, and the electrophoresis of
      DNA isolated from these cells showed characteristic fragmentation, i.e. 'DNA
      ladder'. DNA fragmentation was detectable with UVB doses of more than 50 mJ/cm2,
      and it appeared 12 h after irradiation, indicating endonuclease-mediated DNA
      damage. In vivo experimentation using the TdT-mediated dUTP-biotin nick end
      labeling method (TUNEL) for detection of AC showed scattered positive cells in
      the basal layer of the UVB-irradiated mouse ear skin. The distributed pattern of
      the TUNEL-positive cells was similar to that of SBCs. These findings suggest that
      UVB is a causative factor of apoptosis in the epidermal cells, and that SBC is
      formed as a result of the apoptosis.

PMID- 8740457
TI  - Melanogenesis, biosynthetic phenotype of fibronectin and collagen, and migrating
      activity in cloned B16 mouse melanoma cells.
AB  - Three clones, melanotic (M3), amelanotic (A4 and A7) cells were isolated from B16
      F10 mouse melanoma cell line. These clones exhibited different biosynthetic
      activities of fibronectin and collagen: A4 clone showed relatively active
      synthesis of both collagen and fibronectin, and A7 clone exhibited most active
      fibronectin synthesis, whereas no significant synthesis of these molecules was
      observed in M3 clone. No significant difference in growth rate was observed in
      these three clones. Migrating activities measured by basement membrane matrix
      coated dishes were greater in A7 clone than in A4 and M3 clones. Messenger RNA
      levels of collagen and fibronectin paralleled collagen and fibronectin synthesis
      in these clones whereas tyrosinase mRNA level was unaltered between melanotic
      (M3) and amelanotic (A4 and A7) cells. These results indicate that B16 melanoma
      cells have heterogeneous cell populations consisting of different biosynthetic
      and metastatic properties. These clones may provide good tools for studying the
      relationship between the phenotypes of melanogenesis biosynthesis of
      extracellular macromolecules and migrating activity of melanoma cells.

PMID- 8740458
TI  - UV-induced apoptosis in rat skin.
AB  - Sunburn cells appear in the epidermis after UVB irradiation and are
      histologically suggested to be keratinocytes undergoing apoptosis. We here show a
      known biochemical process of apoptosis, genomic DNA fragmentation, in rat skin.
      UVB irradiation induced sunburn cells in the epidermis of rat skin at a lower
      dosage and the cleavage of genome DNA to nucleosomal size units at dosages of
      more than 0.3 J/cm2. The fragmented DNA observed could be driven from the
      epidermis though the involvement of DNA in dermal cells cannot be neglected. PUVA
      treatment also induced sunburn cells and the fragmentation of genome DNA. The
      extent of DNA fragmentation by UVB irradiation was enhanced depending on the
      dosage and peaked at 12-24 h after the irradiation. The induction of the DNA
      fragmentation observed in this study indicates the presence of a common pathway
      related to the DNA damage-induced apoptosis in the skin, and might become a
      useful marker in the course of in vivo studies on the physiological role of
      apoptotic process in the skin.

PMID- 8740459
TI  - CDw49b/CD29 integrin complex mediates the differentiation of human endothelial
      cells into capillary-like structures in vitro.
AB  - We have investigated different beta-1 integrins (CDw49/CD29) on human umbilical
      vein endothelial cells (HUVEC) with regard to their roles in modifying the
      morphological structure of these cells on/in matrigel. The inhibition of matrigel
      induced capillary formation by antibodies against subunits of beta-1 integrins
      was examined quantitatively using a digital analyzer. Antibodies to CDw49b and
      CD29 (common beta chain) caused a marked inhibition of capillary formation (up to
      70%) in a dose-dependent manner, whereas antibodies to CDw49d, CDw49e and CDw49f
      were less inhibitory. We also examined the appearance of HUVEC cultured in
      matrigel. HUVEC suspended in matrigel for 24 h formed extended cell processes
      which connected, resulting in the formation of a capillary network. In contrast,
      fibroblasts cultured in matrigel showed only bipolar extensions without cell-cell
      contact. After 48 h in culture in matrigel, some HUVEC showed the capillary-unit
      of a lumen encircled by EC which may mimic the basic putative unit in the
      formation of capillaries. However, HUVEC pretreated with antibodies to CDw49b and
      CD29 failed to form significant processes and a hollow lumen. These phenomena may
      illustrate the importance of endothelial cell-basement membrane matrix
      interaction (through integrins, especially CDw49b/CD29 complex) occurring during
      differentiation of endothelial cells in angiogenesis.

PMID- 8740460
TI  - Butylated hydroxyanisole blocks the inhibitory effects of tumor necrosis factor
      alpha on collagen production in human dermal fibroblasts.
AB  - Tumor necrosis factor-alpha (TNF-alpha) has been demonstrated to selectively
      decrease the production of type I and type III collagens in human dermal
      fibroblasts. The effects of the commonly used food antioxidants, butylated
      hydroxyanisole (BHA), butylated hydroxytoluene (BHT), alpha-tocopherol, propyl
      gallate, superoxide dismutase (SOD), and catalase on TNF-alpha-induced growth
      enhancement and collagen metabolism were evaluated in the present study. BHA at
      concentrations of both 5 x 10(-5) and 10(-4) M inhibited cell proliferation and
      DNA synthesis induced by 10 ng/ml TNF-alpha in human dermal fibroblasts, while
      other antioxidants had minimal effects. Further, BHA (5 x 10(-5) M and 10(-4) M)
      significantly blocked TNF-alpha-induced decreases in collagen synthesis. These
      results suggest that antioxidants such as BHA may be involved in the modulation
      of collagen synthesis by TNF-alpha in human dermal fibroblasts.

PMID- 8740461
TI  - Topical treatment of cutaneous herpes simplex virus-1 infection in mice with a
      specially formulated caffeine gel (Cafon).
AB  - Caffeine, although not a nucleoside analog, is known to inhibit the replication
      of herpes simplex virus-1 (HSV-1) and has been shown to significantly limit the
      spread of HSV infection in vitro. The therapeutic efficacy of caffeine was
      examined in a murine cutaneous infection model. The midflanks of 6-week-old
      BALB/c mice were infected with HSV cutaneously after application of 10% caffeine
      (Cafon) gel, and was reapplied to the midflank 5 times daily thereafter.
      Treatment with Cafon gel significantly retarded the development of skin lesions.
      Both midflanks were cutaneously infected, and a placebo and active gel were
      applied to the right and left midflanks respectively. Cafon gel significantly
      retarded the appearance of vesiculation and reduced the number of vesicles
      compared with the placebo gel. Cafon gel was as effective as 5% acyclovir
      ointment, and no significant difference was observed in the development of local
      lesions between these two topical preparations. The efficacy of Cafon gel also
      corresponded to that of oral treatment with 5 mg/kg or more of acyclovir in our
      cutaneous infection system. These results suggest that Cafon gel can be useful
      for the topical treatment of cutaneous HSV infection.

PMID- 8740462
TI  - The relationship between quantitative changes in collagen and formation of
      wrinkles on hairless mouse skin after chronic UV irradiation.
AB  - Female albino hairless mice were irradiated chronically with sub-erythemal doses
      of UVB radiation. Collagen extracted from the irradiated or non-irradiated dorsal
      skin of mice was fractionated into neutral salt-soluble (NSC), acid-soluble (ASC)
      and insoluble fractions (ISC). An age-related exponential decrease in the content
      and proportion of acid-soluble collagen was found in each group. The contents and
      the proportions of ASC from irradiated mice were always significantly lower than
      those from age-matched control animals. Age-related slight decreases were
      observed in the contents (per fresh weight of tissues) of NSC, ISC and total
      collagen in the control group but decreases in these collagen contents after UVB
      irradiation were marked. A dramatic decrease in ASC occurred nearly concomitantly
      with wrinkle formation in the irradiated mice. The decrease of acid-soluble skin
      collagen in irradiated mice may play a role in the formation of wrinkles on
      hairless mouse dorsal skin.

PMID- 8740463
TI  - Effect of a chemically-synthesized acylglucosylceramide, epidermoside, on normal
      human keratinocyte differentiation.
AB  - Epidemosides (N-(0-linoleoyl)-(1)-hydroxy fatty acyl sphingosyl glucose) are
      found exclusively in the epidermis not in dermis, and are thought to play
      important role in forming the mammalian epidermal permeability barrier. A species
      of epidermoside isolated from guinea pig epidermis and named lipokeratinogenoside
      has been shown to enhance fetal rat keratinocyte differentiation. In the present
      investigation, we studied the effects of a chemically synthesized equivalent of
      human epidermoside on the viability and differentiation of cultured human
      keratinocytes (HK Cells). The chemically-synthesized epidermoside was not toxic
      to cultured HK Cells at concentrations of 0.01 to 10 micrograms/ml. When 10
      micrograms/ml of the chemically-synthesized epidermoside was added to
      keratinocyte growth medium containing 1.2 mM Ca2+, HK Cells showed a 5.6-fold
      increase of keratin content compared to the vehicle treated control at 144 h of
      cultivation, and they also displayed morphological changes suggestive of
      differentiation. A similar increase of cellular keratin content was observed in
      HK cells treated with tetradecanoyl phorbol-13 myristyl-12 acetate (TPA), an
      agent known to enhance the differentiation of keratinocytes. Lipokeratinogenoside
      also increased the keratin content of cultured HK cells. These results suggest
      that epidermosides have an ability to enhance keratinocyte differentiation.
      Epidermoside could thus be a key molecule, not only as a constituent of the
      epidermal permeability barrier, but also as a regulator of keratinocyte
      differentiation.

PMID- 8740464
TI  - Lineage-specific CaN19 expression in human skin: lack of expression in normal
      melanocytes.
AB  - Although expression of CaN19 is reduced in cell lines derived from tumors of
      diverse origin, its expression in their normal counterparts has not been studied
      in detail. We find that CaN19 mRNA is expressed at very low to undetectable
      levels in normal melanocytes as well as malignant melanoma cell lines, confirming
      that CaN19 expression in normal cells is lineage-dependent.

PMID- 8740465
TI  - Soluble form of vascular cell adhesion molecule-1 in systemic lupus erythematosus
      and discoid lupus erythematosus.

PMID- 8740466
TI  - Development and preliminary testing of a brief intervention for modifying CHD
      predictive hostility components.
AB  - Hostility is an independent risk factor for coronary heart disease (CHD), and
      certain hostility subscales (e.g., Barefoot's refined Ho) predict CHD and
      mortality more powerfully than global hostility measures. An intervention for
      modifying CHD-predictive hostility components was developed and tested. Twenty
      two healthy, high-hostile males, who were matched on age and hostility level,
      were randomly assigned to either an experimental hostility-reduction treatment
      group or an information-control group. The experimental group received eight 90
      min weekly sessions for altering antagonism, cynicism, and anger reactions. After
      controlling for pretreatment levels, subjects' group status accounted for an
      additional and significant 28 and 19% of the variance in improvement of observed
      Anger-Out scores and Barefoot's refined Ho scores, respectively. Thus, this
      treatment may reduce CHD-predictive and mortality-predictive hostility levels.
      The possible clinical significance of these results was tested, and future large
      scale and long-term trials are recommended.

PMID- 8740467
TI  - Positive and negative psychosocial sequelae of bone marrow transplantation:
      implications for quality of life assessment.
AB  - Life-threatening disease can trigger positive effects such as greater
      appreciation for life and enhanced interpersonal relationships. Little research
      has examined these salutary effects or their association with quality of life
      (QOL). Adult bone marrow transplantation (BMT) survivors (n = 90) were
      interviewed regarding psychosocial sequelae of BMT and completed indices of QOL
      and psychological adjustment. Thematic analysis was used to code interview
      responses into discrete categories of negative and positive sequelae. Multiple
      regression analyses indicated POSTOTAL scores were inversely associated with time
      post-BMT and positively associated with negative prognostic factors at BMT.
      Scores on indices of QOL and psychological adjustment were significantly
      correlated with reports of negative post-BMT sequelae but unrelated to positive
      sequelae. It was concluded that life-threatening disease can trigger positive
      sequelae that can contribute to QOL. However, standard QOL indices may not
      measure this positive QOL dimension, thus yielding a potentially incomplete
      picture of current QOL.

PMID- 8740468
TI  - Individual differences in the perception of optimism and disease severity: a
      study among individuals with Parkinson's disease.
AB  - The extent to which individuals with Parkinson's disease (PD) show lability in
      optimism was explored in the present study. The relationship between optimism and
      perceived disease severity was examined as well. Twelve individuals diagnosed
      with PD completed self-report measures for 70 consecutive days. All individuals
      in this study showed lability in optimism over short time periods; however, 67%
      of the sample showed no pervasive negative changes in optimism over time.
      Increased levels of optimism on one day were predictive of decreased perceived
      disease severity the next day for one-fourth of the sample, after controlling for
      negative affect. Individual differences in the relationship between optimism and
      disease severity provided support for the idea that living with chronic illness
      has no monolithic meaning. More optimistic individuals reported less need for
      assistance with basic functional abilities than less optimistic individuals. The
      usefulness of lability in optimism among individuals with PD is discussed.

PMID- 8740469
TI  - Psychometric properties of the Weekly Stress Inventory (WSI): extension to a
      patient sample with coronary heart disease.
AB  - The psychometric characteristics of the Weekly Stress Inventory (WSI) were
      examined in a sample of medical patients (N = 84) diagnosed with coronary heart
      disease. In addition to the WSI, patients completed measures assessing recent
      depressive symptoms, physical symptoms, Type A behavior, and trait anxiety.
      Patients also monitored stress for 3 weeks (n = 46), completing the Daily Stress
      Inventory (a measure of minor stress) daily and the WSI at concurrent 1-week
      intervals. Results indicated that the WSI is an internally consistent and
      moderately stable measure. Validity of the WSI was supported by (a) strong
      correlations with a concurrently administered measure of minor stress (concurrent
      validity); (b) significant positive correlations with measures assessing recent
      depressive symptoms, physical symptoms, and Type A behavior; and (c) a lack of
      relationship with a measure of trait anxiety (discriminant validity).

PMID- 8740470
TI  - Parenting style and adolescent depressive symptoms, smoking, and academic
      achievement: ethnic, gender, and SES differences.
AB  - This paper examines whether the relationship between parenting style and
      adolescent depressive symptoms, smoking, and academic grades varies according to
      ethnicity, gender, and socioeconomic status. Four parenting styles are
      distinguished, based on patterns of parent-adolescent decision making: autocratic
      (parents decide), authoritative (joint process but parents decide), permissive
      (joint process but adolescent decides), and unengaged (adolescent decides). The
      sample included 3993 15-year-old White, Hispanic, African-American, and Asian
      adolescents. Results are generally consistent with previous findings: adolescents
      with authoritative parents had the best outcomes and those with unengaged parents
      were least well adjusted, while the permissive and the autocratic styles produced
      intermediate results. For the most part, this pattern held across ethnic and
      sociodemographic subgroups. There was one exception, suggesting that the
      relationship between parenting styles, especially the unengaged style, and
      depressive symptoms may vary according to gender and ethnicity. More research is
      needed to replicate and explain this pattern in terms of ecological factors,
      cultural norms, and socialization goals and practices.

PMID- 8740471
TI  - Cigarette smoking and the intention to quit among pregnant smokers.
AB  - Research has demonstrated that smoking during pregnancy has deleterious effects
      on the health of the unborn child as well as the mother. The present study
      examined whether pregnant smokers would have a greater intention to quit smoking,
      whether the stage of pregnancy would influence the intention to quit, and whether
      variables which have predicted cessation among pregnant smokers would also
      predict intention to quit. The results indicated that pregnant women did not have
      a significantly greater intention to quit smoking compared to nonpregnant
      smokers, despite the health risks to their child. Women who were further along in
      their pregnancy and women who smoked more cigarettes on a daily basis
      demonstrated the least intention to quit. Notably, women in the first trimester
      showed the greatest intention to quit, suggesting that pregnant women may be most
      receptive to quitting during their first trimester.

PMID- 8740472
TI  - Variations and topography of the arteries in the lesser omentum in humans.
AB  - Modern surgical techniques depend in part on knowledge of both the "normal" and
      the anomalous arterial blood supply. For instance, in liver transplantation,
      during surgery of the gallbladder, gastrectomy, and gastric lymphadenectomy, or
      when selective arterial chemotherapy is used for treatment of liver cancer,
      aberrant hepatic arteries can be a significant problem. A series of 138 cadavers
      with arterial latex injection were dissected and 10 corrosion casts were made to
      obtain an exact knowledge of the topography of the normal and anomalous arteries
      of the lesser omentum in humans. The so-called normal anatomy was found in only
      9% (15 of 148 individuals), the remaining five-sixths presenting some variations
      from this, many of direct surgical importance. In these cases one or two aberrant
      hepatic arteries (37%), an artery in the free border of the hepatoduodenal
      ligament (19%), a right hepatic artery crossing the portal vein posteriorly (4%),
      the right hepatic artery entering the triangle of Calot anteriorly (29%) or not
      (7%), or an accessory left gastric artery branching off the left hepatic artery
      (2%) were found.

PMID- 8740473
TI  - Clinical importance of the minimal cancellous diameter of lower thoracic and
      lumbar vertebral pedicles.
AB  - Transpedicular spinal fixation is a widely used method in vertebral surgery, but
      it suffers from complications due to mismatches between the screw and pedicle.
      Therefore, information on minimal cancellous (MCD) and minimal external diameters
      (MED) of the pedicle is highly important for vertebral surgery. To determine
      these diameters and their ratios, 2,808 measurements of 1,404 pedicles of 702
      human vertebrae were made from Th11 to L5. We found that the mean ratio of MCD to
      MED was 72.2%, MCD to vertical diameter (VD) was 41.7%, and MCD to transverse
      diameter (TD) was 62.2% in all levels. We recommend that these results be
      considered prior to pedicular fixation operations and design of new implantable
      devices.

PMID- 8740474
TI  - The arterial anatomy of larynx transplantation: microsurgical revascularization
      of the larynx.
AB  - Advances in immunosuppression and selective reinnervation may soon make laryngeal
      transplantation a potential therapy for patients undergoing total laryngectomy.
      Successful transplantation requires a clear delineation of those vessels
      necessary to completely revascularize the larynx. Our hypothesis is that the
      arterial inflow provided by a single superior thyroid artery is sufficient to
      revascularize the entire larynx. To test this hypothesis, 8 cadavers were studied
      via either barium latex injection (n = 4) to assess contralateral tissue
      perfusion or India ink (n = 4), to determine the degree of mucosal perfusion.
      Following injection via a single superior thyroid artery, all larynges
      demonstrated either complete, bilateral tissue perfusion evidenced by x-ray
      visualization of the barium latex injected specimen or bilateral mucosal staining
      with India ink. We conclude that bilateral perfusion of the entire larynx
      transplant, including laryngeal and epiglottic mucosa, would occur after
      revascularization of a single superior thyroid artery. These findings suggest
      that reliable revascularization of a larynx transplant is technically possible
      using modern microsurgical techniques.

PMID- 8740475
TI  - An unusual origin for the accessory head of biceps brachii muscle.
AB  - During the superficial dissection of the pectoral region and the arm, an abnormal
      biceps brachii muscle was observed unilaterally. This muscle had three heads.
      Whereas the short and long heads had their normal origin, the accessory head
      originated from the anterior surface of the distal part of the pectoralis major
      muscle, which formed the anterior axillary fold. To our knowledge, this variation
      has not been previously described. Innervation and vascular supply of this
      accessory head was from the musculocutaneous nerve and the brachial artery,
      respectively.

PMID- 8740476
TI  - Basic surgical training. 1: Postgraduate surgical examinations in the UK and
      Ireland.
AB  - This report is concerned with the place of the basic medical sciences, and
      particularly of anatomy, in the training of surgeons in the UK and Ireland. It
      reviews the present arrangements and their perceived shortcomings and outlines
      the proposals for a new 2-year program of Basic Surgical Training drawn up by the
      four Royal Colleges of Surgery in the UK and Ireland. The new proposals severely
      restrict the time available to surgical trainees for study of anatomy, exposure
      to which has already been drastically curtailed in the undergraduate medical
      course. Although it is intended by the Royal Colleges that specialized anatomy
      appropriate to the various surgical specialties will be examined during Higher
      Surgical Training, the author contends that anatomy as it applies to all aspects
      of surgery must be learned and examined thoroughly during Basic Surgical
      Training. Examination by MCQs' alone is not enough: there is a need for practical
      assessment in the final assessment at the end of Basic Surgical Training, and
      this should involve anatomists as well as surgeons. Surgical skills are built
      upon anatomical knowledge, the study and examination of which must not be reduced
      to a level where it is detrimental to the care of patients.

PMID- 8740477
TI  - Basic surgical training. 2: Interactions with the undergraduate medical
      curriculum.
AB  - Proposed changes in postgraduate surgical training must be seen in the context of
      changes being implemented in medical schools. The reorganization of discipline
      based departments into large units of biomedical science; the reduction in time
      allotted to anatomy, particularly to dissection by students; the development of
      integrated courses with multidisciplinary examinations in which poor performance
      in anatomy can be compensated by good marks in other subjects; the decline in
      staff numbers (faculty) with expertise in human anatomy and corresponding
      enthusiasm for teaching it; and the loss of demonstratorships available to
      surgical trainees are all factors that leave today's medical graduates who embark
      upon surgical training programs poorly equipped in their knowledge of anatomy.
      This deficiency is not easily remedied by the proposed changes in Basic Surgical
      Training and is not adequately identified by the examination arrangements. It is
      argued that a structured oral examination with a wide spectrum of components,
      including dissections, living and surface anatomy, osteology, radiographs and
      scans, and microanatomy, would be the best way of assessing the familiarity of
      candidates with anatomy and their suitability to proceed to Higher Surgical
      Training.

PMID- 8740478
TI  - Basic surgical training. 3: A view from Ireland.
AB  - This report points to the inadequate knowledge of anatomy shown by recent medical
      graduates, now reflected in their poor performance in the oral examination in
      anatomy in Part A of the FRCSI examination. Although it seems likely that the new
      examination for the Associate Fellowship of RCSI will retain an oral examination
      in surgical anatomy, the lack of recognition of a demonstratorship in anatomy as
      part of the Basic Surgical Training program will deter good applicants for these
      posts, which will in turn further weaken undergraduate teaching of anatomy.

PMID- 8740479
TI  - Basic surgical training. 4: American and British scenes compared.
AB  - This report outlines the surgical residency program in the United States, with
      special reference to examinations in anatomy. During each of the 5-6 years of the
      program and in the first part of the surgical board examination, there are
      written (MCQ) examinations. The final board examination is oral. The anatomic
      content of each of these examinations is very small. This situation compares
      unfavorably with that in the UK in the 1940s and 1950s, when the colleges of
      surgeons demanded a high standard of anatomic knowledge, so that holders of the
      Fellowship (FRCS) displayed confidence in their diagnostic skills and in the
      operating room. In the United States today, surgical residents and attending
      surgeons (British = consultants) alike seldom have a sound overall knowledge of
      anatomy. They may become proficient in localized regions, but when drawn out of
      their area of expertise, their anatomic knowledge may be less than expert. It is
      disappointing to learn that the surgical colleges in the UK and Ireland are
      making changes in their Basic Surgical Training program that will inevitably
      result in a decline from their former high standards.

PMID- 8740480
TI  - Preclinical student reactions to dissection, death, and dying.
AB  - The objective of the present study was to determine the reactions of preclinical
      medical students to dissection; cognate issues. A questionnaire was administered
      to a class of 148 students; the stimulus items inquired about the frequency of
      mental and physical symptoms, causes of stress, degree of upset occasioned by
      dissection, previous encounters with death, mental preparedness at the
      commencement of the course, reactions to dissecting room activities, coping
      strategies, and the desirability of a course on death and dying. Nearly a quarter
      of the sample reported an increase in the frequency of mental and physical
      symptoms. A third of the students identified the dissecting room as a "very
      important" stressor. Only for female respondents were "dissecting room" and
      "great difficulty of work" significantly associated as causes of stress. Over
      three-quarters of the students were upset at the beginning of dissection and
      about a third remained disturbed after 101.5 hours. Sixty students had seen a
      dead body previously and 30 students had been bereaved within the 2 years
      preceding the study. However, neither prior exposure to a dead body nor
      bereavement was a safeguard against persistent upset by dissection. The initial
      reactions were mostly negative, but neutral and positive attitudes later
      supervened. The coping strategies cited did not suggest any significant
      distortion attributable to the unseemly origins of the cadavers. A compulsory
      formal course on death and dying during both preclinical and clinical stages was
      considered desirable by the majority of respondents, more for personal and
      clinical reasons than for dissection-related ones.

PMID- 8740481
TI  - Survey of cadaveric donors to a body donation program: 1978-1993.
AB  - Body donation files from the Department of Anatomy at Northeastern Ohio
      Universities College of Medicine were reviewed from the 569 donors used in our
      program from 1978-1993. The data were entered into a computerized database to
      evaluate the characteristics of people who have contributed to the body donation
      program for cadaveric dissection. The purpose of this review was to reveal a
      profile of the people who have contributed to our program and enable us to
      identify any deficiencies or disproportionate representation of donors which can
      be used when targeting future applicants. Donors to our program were
      predominantly male (58%), although there was a clear trend for increasing numbers
      of females over the latter period of the program. Donors were almost exclusively
      white (98%) with an average age at death of 73 years (range 18-98 years). The
      combination cardiovascular (46%), cancer (27%), and pulmonary dysfunction (16%)
      accounted for nearly all deaths of our donors. Approximately half of the donors
      (49%) were married and they completed an average of 12.5 years of education. The
      typical donor bequested at, or near, the time of death. From these data we
      conclude that certain characteristics of our donors can be primarily attributable
      to the population base of our sample. Other characteristics, for example, gender,
      age at death of females, and educational level, show marked departures from
      population values and suggest some unique attributes of our donors. Bequests to
      our body donation program do not appear to represent a long-term plan, but rather
      a decision made just prior to death.

PMID- 8740482
TI  - The vertebral column--a phylogenetic failure? A theory explaining the function
      and vulnerability of the human spine.
AB  - The increase in degenerative diseases of the vertebral column is often attributed
      to an inadequate adaptation to the upright posture in the human. On the basis of
      a precise analysis of the motion segments, an attempt has here been made to
      demonstrate that the design of the vertebrae in both the larger mammals and in
      humans has resulted in no qualitative differences between the stresses to which
      either is subjected. In the course of evolution there has certainly been an
      obvious conflict in aims between the need for essential stability and the desired
      or necessary mobility. These mutually self-limiting mechanisms are reflected in
      the highly specialized architecture of the ligamentous apparatus and vertebral
      joints. We conclude that the human vertebral column seems to be an optimized
      compromise of evolution.

PMID- 8740483
TI  - Must managed care dominate the scene?

PMID- 8740484
TI  - Organized systems of care and psychiatrists' fees.

PMID- 8740485
TI  - Physician health programs and the potentially impaired physician with a substance
      use disorder.

PMID- 8740486
TI  - The individual placement and support model of supported employment.

PMID- 8740487
TI  - Advantages of working in a capitated mental health system.

PMID- 8740488
TI  - An outcome measure for postdischarge follow-up of residential treatment.

PMID- 8740489
TI  - Predictors of receipt of aftercare and recidivism among persons with severe
      mental illness: a review.
AB  - OBJECTIVE: This paper provides a comprehensive review of research predicting
      receipt of aftercare and recidivism (rehospitalization) among individuals with
      severe and persistent mental illness. METHODS: English-language studies were
      identified by searching PsycLIT from January 1974, the year of a previous
      comprehensive review of the literature on recidivism, to March 1994. A heuristic
      model was used to classify predictor variables into three categories: client
      vulnerability, community support, and system responsiveness. RESULTS: In general,
      variables related to system responsiveness were more consistent predictors of
      receipt of aftercare than variables related to either client vulnerability or
      community support. Community support variables were more consistent predictors of
      recidivism than variables in any of the other categories. Assertive community
      treatment and receipt of aftercare-both system responsiveness variables-were also
      associated with lower rates of rehospitalization. CONCLUSIONS: Conclusions based
      on past research should be regarded as tentative, because of several
      methodological and theoretical weaknesses. Multivariate statistics have rarely
      been used, many of the studies are based on nonrepresentative samples, and
      interactions between client-level variables and system responsiveness variables
      have rarely been studied. Much of the research has relied on archival data, and
      choice of variables has thus often been guided more by the data available than by
      theory.

PMID- 8740490
TI  - "Sylvia Frumkin" has a baby: a case study for policymakers.
AB  - "Sylvia Frumkin" was a pseudonym given to a 32-year-old woman with chronic mental
      illness described by Susan Sheehan in her books Is There No Place on Earth for
      Me? This paper presents the case of "Gloria Morrison," a patient similar to Ms.
      Frumkin, who is also a mother. Issues raised by the case in three areas are
      discussed. Issues for the service delivery system include developing better
      assessment, prediction, and reduction of the risk that a parent's mental illness
      may pose to a child's safety and well-being; targeting supportive and educational
      interventions to relatives and foster parents caring for children of severely
      mentally ill patients; and tailoring programs and services to the needs of such
      patients and their children. Clinical treatment issues include offering treatment
      options through agencies other than the department of social services; developing
      protocols for the care of severely mentally ill pregnant and postpartum women;
      focusing on issues of loss; and providing parenting skills training. Issues in
      the area of family support include increasing providers' awareness of family
      burden and alleviating conflicts between the family and patient.

PMID- 8740491
TI  - Sexuality, pregnancy, and childrearing among women with schizophrenia-spectrum
      disorders.
AB  - OBJECTIVE: This study compared sexuality, reproduction, and childrearing
      characteristics of women with schizophrenia-spectrum disorders with those of
      women without serious mental illness. METHODS: A semistructured interview was
      given to 46 women meeting Research Diagnostic Criteria for schizophrenia or
      schizoaffective disorder and to 50 control subjects without major mental illness
      who were matched for age, race, education, employment status, and religion.
      RESULTS: Compared with the control subjects, the women with schizophrenic
      disorders had more lifetime sexual partners, were less likely to have a current
      partner, and were more likely to have been raped and to have engaged in
      prostitution. Despite being at high risk for HIV infection, as a group they were
      less likely to have been tested for HIV. They reported wanting sex less often
      than did control subjects and rated their physical and emotional satisfaction
      with sex lower. They had fewer planned pregnancies, more unwanted pregnancies,
      and more abortions and were more often victims of violence during pregnancy. They
      were more likely to have lost custody of children and to report that they were
      unable to meet their children's basic needs and less likely to have another
      caregiver helping them raise their children. Both groups reported high rates of
      substance abuse during pregnancy. CONCLUSIONS: Health care delivery systems could
      better meet the needs of women with severe mental illness by providing social
      skills training, family planning, and more consistent screening for pregnancy,
      HIV, and battering. In addition, barriers to care for pregnant women with severe
      mental illness and substance abuse should be reduced, and parenting training
      should be incorporated into psychosocial rehabilitation programs for mentally ill
      parents.

PMID- 8740492
TI  - Family burden of schizophrenia and bipolar disorder: perceptions of relatives and
      professionals.
AB  - OBJECTIVE: The study compared the burden that specific problem behaviors of
      patients with schizophrenia or bipolar disorder placed on relatives and evaluated
      the accuracy of mental health professionals' judgment of the burden. METHODS: A
      questionnaire was developed to assess the burden of 20 common problem behaviors
      associated with manic, positive, and negative symptoms. The questionnaire was
      given to 48 relatives of patients with schizophrenia or bipolar disorder. In
      addition, 39 mental health professionals completed separate questionnaires
      indicating the amount of burden they believed relatives experienced due to these
      behaviors. RESULTS: Relatives of patients with bipolar disorder rated manic
      symptoms as more burdensome than did relatives of patients with schizophrenia,
      but relatives of patients in the two groups did not differ in their ratings of
      burden associated with positive or negative symptoms. Professionals' perceptions
      of the burden associated with manic symptoms were relatively accurate, but they
      tended to underestimate the burden of positive and negative symptoms experienced
      by relative of patients with bipolar disorder. CONCLUSIONS: Psychiatric diagnosis
      may be of limited value in understanding the burden relatives experience due to
      specific psychiatric symptoms. Professionals are encouraged to assess the burden
      that is associated with specific problem behaviors regardless of psychiatric
      diagnosis.

PMID- 8740493
TI  - Columbia University's fellowship in public psychiatry.
AB  - In 1981 the fellowship in public psychiatry was established at New York State
      Psychiatric Institute and Columbia University College of Physicians and Surgeons
      to provide subspecialty training for psychiatrists who plan careers in the public
      sector. Ten one-year postresidency fellowships are awarded annually. The
      fellowship consists of supervised work and didactic experiences focused on the
      clinical modalities most effective in public mental health services and the
      managerial skills that the psychiatrist must possess to make those services work
      well. Fellows work three days a week at collaborating public-sector agencies
      throughout the New York metropolitan area. The curriculum includes an academic
      seminar, which gives fellows an introductory overview of major topics in public
      psychiatry; an organizational practicum, which is an exercise in management
      principles and practices; an evaluation practicum, which addresses the theory and
      practice of program evaluation; and an applied seminar, organized as a cycle of
      clinical, administrative, fiscal, and evaluation presentations in which each
      fellow applies the concepts learned in the other seminars to his or her field
      placement work. Of the 75 fellows who have graduated from the program, only six
      have chosen to leave the public arena. Nearly all work full time in the public
      sector, where more than half hold management positions. More than three-fourths
      hold academic appointments at medical schools in the area in which they are
      working as public psychiatrists.

PMID- 8740494
TI  - Suicide among immigrants from the Indian subcontinent: a review.
AB  - OBJECTIVE: Studies of suicide among immigrants from the Indian subcontinent
      (India, Pakistan, Bangladesh, and Sri Lanka) were examined to increase awareness
      of suicide risk and to better understand social and psychological factors
      contributing to suicide in this group. METHODS: An online search was conducted of
      MEDLINE for the years 1966 to 1994 and Psychological Abstracts for the years 1974
      to 1994, and all references on completed suicides in the target population were
      selected for review. RESULTS: Suicide rates of young women immigrants from the
      Indian subcontinent are consistently higher than those of their male counterparts
      and of young women in the indigenous populations of the countries to which they
      immigrate. Suicide rates among older men in this immigrant group have been
      reported to be low, although reports are less consistent. Use of violent methods
      such as hanging, burning, and poisoning is common among both men and women. A
      disproportionately higher number of immigrant Hindus commit suicide. Family
      conflict appears to be a precipitating factor in many suicides, whereas mental
      illness is rarely cited as a cause. Depression, anxiety, and domestic violence
      may contribute to the high rates. Affective disorders may be underdiagnosed in
      this population. CONCLUSIONS: More research is needed on the epidemiology of
      psychiatric illnesses and their contribution to suicide in this group.

PMID- 8740495
TI  - A model for psychiatric services in primary care settings.
AB  - The integration of mental health care and primary medical care enhances the
      quality of patient care and may improve the overall cost-effectiveness of a
      health care system. The authors describe implementation of a program that
      provides mental health care at 12 locations in a network of primary care sites
      associated with a university-affiliated community hospital in Rochester, New
      York. A project of the hospital's department of psychiatry, the program has as
      its goals improved recognition, diagnosis, and treatment of mental health
      problems and education of primary care providers in these areas. Each of the
      program's three primary therapists provide short-term, symptom-focused
      individual, marital, family, and group therapies and case consultation at several
      primary care sites. The program director, a psychiatrist, makes diagnostic
      assessments and provides medication consultation to both the primary therapists
      and the primary care physicians. The authors discuss the advantages and
      disadvantages of the program model and plans for its future development.

PMID- 8740496
TI  - Partial hospitalization at night: the Brussels Nighthospital.
AB  - This paper describes the Brussels Nighthospital, which has offered partial
      hospitalization to young chronic psychiatric patients since 1978. The hospital's
      rehabilitation program provides evening treatment and nighttime accommodations to
      approximately 44 individuals, who live in the facility for about a year. During
      the day patients are engaged in useful activities outside the facility. The night
      hospital has developed a network of such placements. Psychotherapy and family
      support groups are also offered. A follow-up study of 120 patients (mean time
      after discharge = 4.2 years) showed that most maintained their achieved level of
      adaptation and continued to live in the community engaged in useful activities.

PMID- 8740497
TI  - Training and experience of psychiatric residents in identifying domestic
      violence.
AB  - Of 221 psychiatric residents at four U.S. medical schools, 145 responded to a
      survey about their training and clinical experience in recognizing domestic
      violence and providing referrals and treatment. Only 28 percent reported
      receiving training in this area. Almost half reported that they asked about
      domestic violence in less than a quarter of their cases involving female
      patients. Fifty-nine percent of respondents did so "only when a problem was
      suspected." Eighty-seven percent had seen at least one case of domestic violence
      in the previous year. Those with training in recognizing domestic violence
      identified significantly more cases. Sixty-five percent of all residents surveyed
      were unable to list a local agency for referral.

PMID- 8740498
TI  - Physical aggression against psychiatric inpatients by family members and
      partners.
AB  - The rate of recent violence against newly admitted psychiatric inpatients by
      partners and family members was assessed. Sixty-nine patients who had a partner
      or contact with a family member participated. A high proportion of respondents
      reported physical victimization by either their partner (62.8 percent) or a
      family member (45.8 percent). Physical abuse was rarely documented in medical
      charts, and most respondents did not consider the violence they experienced to be
      abuse. Almost half of the respondents met criteria for posttraumatic stress
      disorder in response to their physical victimization. The findings underscore the
      importance of assessing recent partner and family violence in the routine
      evaluation of psychiatric patients.

PMID- 8740499
TI  - Increasing staff knowledge of and improving attitudes toward patients with
      borderline personality disorder.
AB  - This study examined the effect of a self-instructional program on nurses'
      knowledge of and attitudes and behavioral intentions toward patients with
      borderline personality disorder. The sample consisted of registered nurses
      working on inpatient psychiatric units of general hospitals: 19 in the
      experimental group and 13 in the control group. The Questionnaire on Borderline
      Personality Disorder was administered before and after nurses completed the
      program. Significant postintervention differences in knowledge of and attitudes
      toward patients with the disorder were found between the experimental group and
      the control group. Self-instruction may improve nurses' care of patients with
      borderline personality disorder.

PMID- 8740500
TI  - Neuroleptic dosage in psychiatric outpatients.

PMID- 8740501
TI  - Administrative mentors for psychiatrists.

PMID- 8740502
TI  - Prevalence of serious mental illness among American adults estimated at 5.7
      percent in 12-month period.

PMID- 8740503
TI  - Clinton's 1997 budget includes small increases for research, cuts in funds for
      service programs.

PMID- 8740504
TI  - Diagnostic value of molecular forms of prostate-specific antigen for female
      breast cancer.
AB  - OBJECTIVES: To examine the diagnostic value of prostate-specific antigen (PSA)
      subfractions in the serum of female breast cancer patients. DESIGN AND METHODS:
      PSA subfractions (free PSA, F-PSA; PSA bound to alpha 1-antichymotrypsin, PSA
      ACT) were determined in the serum of patients with breast cancer and in the serum
      of healthy women. Serum was injected into a high-performance liquid
      chromatography column and all fractions were analyzed for PSA using a highly
      sensitive PSA immunofluorometric assay. We studied 3 normal male sera, 3 sera
      from prostate cancer patients who underwent radical prostatectomy (all for
      comparative purposes), 3 sera from healthy women, 3 sera from women with breast
      cancer obtained presurgically, and 7 sera from women with breast cancer,
      postsurgically. RESULTS: All male sera contained mostly PSA-ACT complexes and
      very little free PSA. Sera from all healthy women also contained mostly PSA-ACT
      complexes and nondetectable or traces of free PSA. All 3 presurgical sera from
      patients with breast cancer contained predominantly free PSA. Patients who had
      surgical resection of the breast tumor and were in remission had postsurgical
      serum PSA subfractions similar to those of healthy women (i.e., mostly PSA-ACT
      complexes). CONCLUSION: The serum PSA subfractions of breast cancer patients are
      substantially different from serum PSA subfractions of male patients, healthy
      females, and females who have apparently been treated successfully for breast
      cancer. These findings may form the basis for a serological diagnostic test for
      breast cancer.

PMID- 8740505
TI  - Molecular diagnosis of genetic diseases.

PMID- 8740506
TI  - Assessment of iron status.
AB  - OBJECTIVE: To review the clinical assessment of iron deficiency and excess.
      CONCLUSIONS: Two key iron-related proteins in the human body are ferritin which
      is the iron storage protein, and the transferrin receptor, which controls the
      entry of iron-bearing transferrin to cells. Intact ferritin and truncated
      transferrin-receptor molecules are present in serum in direct quantitative
      proportion to their total tissue content. Ferritin and transferrin-receptor
      production are precisely and reciprocally regulated at a posttranscriptional
      level. This is achieved by an iron-responsive element-binding protein that
      interacts with iron-responsive elements in the mRNA of each, but with contrary
      effects. Increases in serum ferritin reflect increased storage iron and increases
      in serum transferrin receptor reflect cellular iron deficits. The combined use of
      these two measurements allows accurate definition of the entire range of body
      iron status. This is valid even in situations where assessment of iron status has
      been notoriously problematic, including periods of rapid growth, in pregnancy, in
      conditions associated with inflammation, and in trained athletes.

PMID- 8740507
TI  - Evaluation of the CLINITEK ATLAS for routine macroscopic urinalysis.
AB  - OBJECTIVES: To evaluate the performance of a new, benchtop, fully automated urine
      analyzer the CLINITEK ATLAS and compare it with the URICHEM 1000 CHEMSTRIP UA
      analyzer. Macroscopic analysis included measurement of 8 urine analyte
      chemistries and specific gravity by the refractive index method (SgRl). METHODS:
      The analytical performance studies conducted were calibration stability,
      precision (within-run and day-to-day), comparison of results of 437 fresh patient
      urine specimens, analysis of time performance, and problem logging over a 16-day
      evaluation period. RESULTS: Satisfactory calibration reproducibility, within-run
      (n = 10), and day-to-day (n = 16) precision was found because results fell within
      the +/- one color-block by the proposed National Committee for Clinical
      Laboratory Standards (NCCLS) criteria. Patient results (n = 437) from the 2
      analyzers giving the same color-block agreement was found to be for pH, 52%;
      glucose, 92%; ketones, 86%; protein, 79%; bilirubin, 97%; leukocytes, 72%; blood,
      80%; and nitrite, 98%. The concordance defined by the NCCLS criteria as the
      agreement of results +/- one color-block between the 2 analyzers was found to be
      for pH, 96%; glucose, 99%; ketones, 100%; protein, 95%; bilirubin, 100%;
      leukocytes, 97%; and blood 86%. The SgRl determined on ATLAS was correlated with
      the RD-10 Rapid Density analyzer with the following results: slope = 0.97,
      intercept = 0.033, r = 0.94, Syx = 0.003, for a range of values from 1.002 to
      1.070. CONCLUSION: Our preliminary data indicate that the analytical performance,
      and automatable features for complete walk-away function of this analyzer can
      significantly increase the overall testing efficiency in the urinalysis
      laboratory.

PMID- 8740508
TI  - A simplified method for the analysis of hydroxyproline in biological tissues.
AB  - A critical study of the different steps involved in previous procedure for
      hydroxyproline assay allows the direct measurement of collagen content in tissue'
      homogenates without losing the advantages of the method. The procedure is based
      on alkaline hydrolysis of the tissue homogenate and subsequent determination of
      the free hydroxyproline in hydrolyzates. Chloramine-T was used to oxidize the
      free hydroxyproline for the production of a pyrrole. The addition of Ehrlich's
      reagent resulted in the formation of a chromophore that can be measured at 550
      nm. Optimal assay conditions were determined using tissue homogenate and purified
      acid soluble collagen along with standard hydroxyproline. Critical parameters
      such as the amount of chloramine-T, sodium hydroxide, p
      dimethylaminobenzaldehyde, pH of the reaction buffer, and length of oxidation
      time were examined to obtain satisfactory results. The method has been applied to
      samples of tissue homogenate and purified acid soluble collagen, with recovery of
      added hydroxyproline of 101 +/- 6.5 and 104 +/- 6.0 (SD) percent, respectively.
      The method is highly sensitive and reproducible when used to measure the imino
      acid in tissue homogenates. The modified hydroxyproline assay presented in this
      communication will be useful for routine measurement of collagen content in
      extracts of various tissue specimens. In addition, the modified method can be
      used for batch processing of column fractions to monitor the collagen
      concentrations during purification.

PMID- 8740509
TI  - Quantification of osteopontin in human plasma with an ELISA: basal levels in pre-
      and postmenopausal women.
AB  - OBJECTIVES: To develop an immunoassay for osteopontin (OPN), a secreted
      phosphoglycoprotein that is implicated in a number of human diseases, and
      establish basal plasma OPN levels in healthy women. DESIGN AND METHODS: An
      antigen-capture ELISA was developed to quantity OPN in plasma using a combination
      of mouse monoclonal and rabbit polyclonal antibodies. Basal OPN levels were
      determined in blood plasma of 21 pre- and 14 postmenopausal women obtained at 7
      day intervals over a 4-week period. RESULTS: A group of 35 healthy women had a
      median OPN level of 31 micrograms/L (range = 14-64 micrograms/L). Comparison
      between pre- and postmenopausal women showed that their 4-week average OPN levels
      did not differ significantly (p > 0.16, Mann-Whitney test), and that levels in
      each premenopausal individual remained constant during the menstrual cycle,
      unaffected by cyclical levels of leuteinizing hormone and progesterone.
      CONCLUSION: Systematic quantification of plasma OPN can now be done by ELISA,
      which was used to establish basal plasma OPN levels in a group of healthy women.
      Levels in pre- and postmenopausal women appeared relatively stable over a 4-week
      period.

PMID- 8740510
TI  - Slow beta-migrating lipoprotein: an atherogenic subclass of low density
      lipoproteins.
AB  - OBJECTIVE: To clarify the possibility that midband Lp in LDL fractions might act
      as an atherogenic lipoprotein in their interaction with macrophages. DESIGN AND
      METHODS: Low density lipoproteins (LDL) isolated by zonal ultracentrifugation
      from midband lipoprotein-positive serum in type lib hyperlipidemics were
      subjected to polyacrylamide gel disc electrophoresis. RESULTS: A part of midband
      lipoprotein was observed between pre beta-and beta-band, in addition to the main
      beta-band. We named this midband lipoprotein "slow beta-migrating Lp (slow beta
      Lp)." The larger LDL subfraction from midband-lipoprotein positive serum on
      Sepharose 2B column chromatography contained much slow beta-Lp, named slow beta
      Lp-rich LDL. The smaller LDL subfraction contained a little slow beta-Lp, named
      slow beta-Lp-poor LDL. Slow beta-Lp-rich LDL had similar composition to the
      control LDL except for apolipoprotein E. The uptake of [3H]cholesteryl linoleate
      labeled slow beta-Lp-rich LDL by J774 macrophages was higher than that of control
      LDL. The cholesterol ester content of J774 macrophages incubated with slow beta
      Lp-rich LDL increased significantly compared with slow beta-Lp-poor LDL, beta
      VLDL, and control LDL. CONCLUSION: These results suggest that slow beta-Lp in
      type llb might generate foam cells from macrophages in atherosclerotic lesions.

PMID- 8740511
TI  - Erythrocyte Na+, K+ and Ca2+, Mg(2+)-ATPase activities in hypertensives on
      angiotensin-converting enzyme inhibitors.
AB  - OBJECTIVE: To investigate erythrocyte membrane Na+, K(+)- and Ca2+, Mg(2+)-ATPase
      activities in newly diagnosed hypertensive patients before and after 2, 4, and 6
      months of treatment with enalapril or captopril as monotherapy. METHODS AND
      RESULTS: Na+, K(+)-ATPase activity (nmol ATP hydrolysed/min per mg protein) rose
      by 6 months of treatment in both groups when values were compared in each treated
      group over time (4.5 +/- 0.8 to 9.9 +/- 1.2; 4.9 +/- 0.8 to 10.5 +/- 1.7,
      respectively, p < 0.001 for both). When the treated groups were compared with
      controls at each period of time, Na+, K(+)-ATPase activity was higher at months 4
      and 6 (p < 0.001) for both groups, respectively). Ca2+, Mg(2+)-ATPase activity
      (nmol ATP hydrolyzed/min per milligram protein) in the absence and in the
      presence of calmodulin increased in the enalapril (6.4 +/- 0.7 to 8.9 +/- 0.95, p
      < 0.05; 13.4 +/- 1.2 to 17.2 +/- 1.2, p < 0.05, respectively) and captopril (7.0
      +/- 0.6 to 8.5 +/- 0.7; 14.4 +/- 1.1 to 16.0 +/- 1.0, p < 0.05, respectively)
      groups after 6 months of treatment compared within each treated group over time.
      When patient groups were compared with controls at time 0, 2, 4, and 6 months,
      the pump activity was higher in the treated groups at 6 months. CONCLUSION: The
      long-term enhancement of cell membrane Na+, K(+)-and Ca2+, Mg(2+)-ATPase activity
      associated with enalapril and captopril therapy may represent a specific effect
      of these agents or alternatively, a nonspecific outcome of blood pressure
      reduction.

PMID- 8740512
TI  - Serum lipoprotein-a levels and glyco-metabolic control in insulin and non-insulin
      dependent diabetes mellitus.
AB  - OBJECTIVES: Conflicting results for lipoprotein-a (Lp(a)) levels in diabetic
      patients exist in the literature. Normal, increased, and decreased values are
      described, and a relation to glycometabolic control is not unequivocally
      established. DESIGN AND METHODS: In our study Lp(a) was measured in a large group
      of diabetiee (80 patients with IDDM and 90 patients with NIDDM) in relation to
      glycometabolic control and the presence of microalbuminuria, retino and/or
      neuropathy. Long-term and short-term glycometabolic control were assessed by HbA1
      and fructosamine assays, respectively. RESULTS: Statistically significant
      differences between Lp(a) levels in IDDM and NIDDM-and a control group of 110
      healthy nondiabetics could not be established. It appeared that the level of
      Lp(a) in IDDM and NIDDM is independent of short-term and long-term glycometabolic
      control or the occurrence of microalbuminuria, neuro or retinopathy. However,
      poor glycometabolic control affected the number of Lp(a) levels elevated above a
      threshold of 0.25 g/L in IDDM. CONCLUSION: These results suggest that the level
      of Lp(a) in serum is not influenced by diabetes mellitus, glycemic control, or
      the occurrence of microalbuminuria, neuro or retinopathy.

PMID- 8740513
TI  - Magnesium fractions in serum of healthy individuals and CAPD patients, measured
      by an ion-selective electrode and ultrafiltration.
AB  - OBJECTIVES: Validation and comparison of a magnesium ion-selective electrode
      (ISE) with a cation-exchange resin technique, followed by determination of all
      magnesium fractions in serum of healthy volunteers and continuous ambulatory
      peritoneal dialysis (CAPD) patients. DESIGN AND METHODS: The analytical aspect
      has been studied by measuring the influence of complexing agents on the fraction
      ionized magnesium (friMg2+). A theoretical approximation of friMg2+, based on
      mass equilibria and complexation constants, was calculated and compared with the
      measurements. RESULTS: ISE measurements showed good agreement with theory.
      Reference values of the ionized, protein-bound, and complexed magnesium fractions
      were (mean +/- SD) 0.65 +/- 0.04, 0.27 +/- 0.04, and 0.08 +/- 0.03, respectively.
      Fractions obtained in the CAPD group were 0.62 +/- 0.04, 0.22 +/- 0.05, and 0.16
      +/- 0.05, respectively, and differed significantly from the values of the
      reference population. CONCLUSIONS: All known serum magnesium parameters can be
      established by a combination of ultrafiltration, atomic absorption spectrometry,
      and ISE measurements. Unknown complexing compounds most probably account for the
      increased fraction of complexed magnesium in the serum of CAPD patients.

PMID- 8740514
TI  - Ret and trk proto-oncogene activation in thyroid papillary carcinomas in French
      patients from the Champagne-Ardenne region.
AB  - OBJECTIVES: To investigate the presence of ret and trk proto-oncogene
      rearrangements in thyroid tumors. DESIGN AND METHODS: High-molecular-weight DNA
      was extracted from 36 thyroid tumors (1 multinodular goiter, 14 follicular
      adenomas, 16 papillary carcinomas, 1 lymph node metastasis of a papillary
      carcinoma, 1 follicular carcinoma, and 3 medullary carcinomas) and 22 adjacent
      tissues. Southern blot analysis was performed after digestion with EcoR1 or
      BamH1, using specific probes for ret and trk. RESULTS: Only 2 ret rearrangements
      were found in 2 papillary carcinomas (overall frequency: 6%; papillary carcinoma
      frequency: 13%). All normal or tumor samples were negative for the presence of a
      trk rearrangement. CONCLUSIONS: The previous data from the literature are highly
      conflicting, ranging from 0 to 30% of activation. Our results could be,
      therefore, classified as medium between these extreme values. It seems,
      therefore, that genetic and/or geographical factors could play a role in ret and
      trk proto-oncogene activation.

PMID- 8740515
TI  - A sub-cybernetic sample handling and analytical system for the clinical chemistry
      laboratory.

PMID- 8740516
TI  - Hypoglycemia is effectively evaluated at the bedside by the Ames Glucometer
      Elite.

PMID- 8740517
TI  - The effect of oxidizing agents and diabetes mellitus on the human red blood cell
      membrane potential.

PMID- 8740518
TI  - Orosomucoid: prealbumin ratio in the monitoring of lung cancer.

PMID- 8740519
TI  - Volunteer bias in human sexuality research: evidence for both sexuality and
      personality differences in males.
AB  - The extent to which personality, social behavior, and sexuality differed in
      undergraduate males under two different types of recruitment, volunteer and
      nonvolunteer, was investigated. Nonvolunteers (N = 160) were ostensibly recruited
      for a study on personality, and volunteers (N = 204) were overtly recruited for a
      study on human sexuality. Both samples completed the same personality, social
      behavior, and sexuality questionnaires. Volunteers were found to be more sexually
      experienced, more interested in sexual variety, and more erotophilic than the
      nonvolunteers. In addition and contrary to most prior research, the volunteer and
      nonvolunteer samples also differed in personality and social behavior, with the
      volunteers being higher in sensation seeking and lower on measures of social
      conformity and rule-following behavior than the nonvolunteers. Results extend
      prior research suggesting limits to the generalizability of some human sexuality
      research.

PMID- 8740520
TI  - Sensation seeking as an explanation for the association between substance use and
      HIV-related risky sexual behavior.
AB  - Past research has shown that recreational drug use correlates with sexual
      behaviors that confer high risk for human immunodeficiency virus (HIV) infection.
      The present study tested the hypothesis that sensation seeking, a disposition
      characterized by the tendency to pursue novel, exciting, and optimal levels of
      arousal, accounts for a majority of the variance in associations between
      substance use and high-risk sexual behavior. Ninety-nine homosexually active men
      completed measures of sensation seeking, self-reported sexual behavior, and
      substance use. Path analysis and hierarchical regression analyses demonstrated
      that sensation seeking accounts for the observed relationship between substance
      use and high-risk sexual behavior. We conclude that personality characteristics,
      often ignored in high-risk sexual episodes, predict risk behavior over and above
      substance use, and may be useful in tailoring HIV prevention interventions.

PMID- 8740521
TI  - Measuring cognitive, affective, and behavioral components of homophobic reaction.
AB  - Comprehensive, reliable, and valid measurement of prejudicial attitudes and
      behaviors toward lesbians and gay males has been identified as a priority. A
      sample of undergraduate (N = 97) and high school students (N = 40) completed
      three reliable measures of cognitive (Modified Attitudes Toward Homosexuality
      Scale), affective (Affective Reactions to Homosexuality Scale), and behavioral
      (Homophobic Behavior of Students Scale) reactions to homosexuals. Undergraduate
      students' responses confirmed the three-factor structure (homophobic guilt,
      homophobic anger, delight) of affects in this domain, and supported the
      concurrent validity of the behavioral measure. Predictive validity of the
      behavioral scale was demonstrated by findings of the high school study which
      showed that students subsequently acted in accordance with their responses to
      this paper-and-pencil test. LISREL confirmatory factor analysis of the
      overarching model indicated that a tripartite (cognition-affect-behavior)
      measurement strategy was appropriate. This strategy may be used in future
      research to provide comprehensive indication of which educational interventions
      make a difference in improving understanding and acceptance of homosexuality.

PMID- 8740522
TI  - Jealousy, general creativity, and coping with social frustration during the
      menstrual cycle.
AB  - Sensitivity to feelings of jealousy in women (n = 16) at three phases of their
      menstrual cycle differing in serum hormone concentrations (menses, preovulatory
      phase, midluteal phase) was investigated. Nonspecific electrodermal activity
      indicating sympathetic excitation was measured while subjects listened to stories
      and imagined situations inducing (i) nonsexual jealousy (the partner forms a deep
      emotional attachment to another woman), (ii) sexual jealousy (the partner has
      sexual intercourse with another woman), and (iii) no jealousy (social interaction
      lacking intense emotionality). Subjective ratings of the intensity of jealousy
      during both stories of jealousy were also assessed. In addition, changes in
      cognitive coping abilities, in general, and in the context of socially
      frustrating events, were assessed by tests of divergent thinking (creativity) and
      the Rosenzweig Picture Frustration Test. Frequency of nonspecific electrodermal
      reactions was generally enhanced during the preovulatory phase. This increase was
      particularly strong when the women listened to stories inducing nonsexual
      jealousy, i.e., a story characterized by cues of a complete loss of the partner's
      investment. Rated jealousy tended to be enhanced during the ovulatory phase,
      especially after the story of nonsexual jealousy. These changes in emotionality
      were paralleled by an improved divergent thinking performance and less aggressive
      coping with socially frustrating events around the time of ovulation.

PMID- 8740523
TI  - Sexual harassment of Chinese college students.
AB  - Sexual harassment of Chinese college students with a focus on their awareness,
      experiences, responses, and expectations of institutional intervention to the
      problem was examined. 358 male and 491 female Chinese college students in Hong
      Kong participated. There were no gender differences in students' awareness of the
      phenomenon. Students' own experiences were less frequent than what they had heard
      about sexual harassment. Peer harassment occurred twice as frequently as faculty
      harassment. Compared to men, twice as many women said they had been sexually
      harassed. About one in four women students experienced various forms of sexual
      harassment and 1% were coerced into sexual activities during their college years
      by either teachers or peers. Students typically avoided and ignored the harassers
      and felt that the university should take up active roles in combating the
      problem. Comparisons with U.S. studies suggested that Chinese college students
      had a lower awareness and experience level in sexual harassment than U.S.
      students.

PMID- 8740524
TI  - Prostaglandin-metabolizing enzymes during pregnancy: characterization of NAD(+)
      dependent prostaglandin dehydrogenase, carbonyl reductase, and cytochrome P450
      dependent prostaglandin omega-hydroxylase.
AB  - Prostaglandins E2 and F2 alpha regulate a number of physiological functions in
      reproductive tissues, and concentrations of these bioactive modulators increase
      during pregnancy. Corresponding to the increase in circulating levels of
      prostaglandins during pregnancy is an increase in enzymes that metabolize these
      agents. Three prostaglandin-metabolizing enzymes induced during pregnancy are
      NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH), NADPH-dependent
      carbonyl reductase, and cytochrome P450-dependent prostaglandin omega- or 20
      hydroxylase. This review discusses the biochemical properties, regulation, and
      possible functions of these three enzymes.

PMID- 8740525
TI  - Protein-protein interfaces: architectures and interactions in protein-protein
      interfaces and in protein cores. Their similarities and differences.
AB  - Protein structures generally consist of favorable folding motifs formed by
      specific arrangements of secondary structure elements. Similar architectures can
      be adopted by different amino acids sequences, although the details of the
      structures vary. It has long been known that despite the sequence variability,
      there is a striking preferential conservation of the hydrophobic character of the
      amino acids at the buried positions of these folding motifs. Differences in the
      sizes of the side-chains are accommodated by movements of the secondary structure
      elements with respect to each other, leading to compact packing. Scanning protein
      protein interfaces reveals that similar architectures are also observed at and
      around their interacting surfaces, with preservation of the hydrophobic
      character, although not to the same extent. The general forces that determine the
      origin of the native structures of proteins have been investigated intensively.
      The major non-bonded forces operating on a protein chain as it folds into a three
      dimensional structure are likely to be packing, the hydrophobic effect, and
      electrostatic interactions. While the substantial hydrophobic forces lead to a
      compact conformation, they are also nonspecific and cannot serve as a guide to a
      conformationally unique structure. For the general folding problem, it thus
      appears that packing is a prime candidate for determining a particular fold.
      Specific hydrogen-bonding patterns and salt-bridges have also been proposed to
      play a role. Inspection of protein-protein interfaces reveals that the hallmarks
      governing single chain protein structures also determine their interactions,
      suggesting that similar principles underlie protein folding and protein-protein
      associations. This review focuses on some aspects of protein-protein interfaces,
      particularly on the architectures and their interactions. These are compared with
      those present in protein monomers. This task is facilitated by the recently
      compiled, non-redundant structural dataset of protein-protein interfaces derived
      from the crystallographic database. In particular, although current view holds
      that protein-protein interfaces and interactions are similar to those found in
      the conformations of single-chain proteins, this review brings forth the
      differences as well. Not only is it logical that such differences would exist, it
      is these differences that further illuminate protein folding on the one hand and
      protein-protein recognition on the other. These are also particularly important
      in considering inhibitor (ligand) design.

PMID- 8740526
TI  - Molecular dissection of the nuclear pore complex.
AB  - The nuclear pore complex (NPC) is an approximately 120 megadalton (MDa)
      supramolecular assembly embedded in the double-membraned nuclear envelope (NE)
      that mediates bidirectional molecular trafficking between the cytoplasm and the
      nucleus of interphase eukaryotic cells. The structure of the NPC has been studied
      extensively by electron microscopy (EM), and a consensus model of its basic
      framework has emerged. Over the past few years, there has been significant
      progress in dissecting the molecular constituents of the NPC and in identifying
      distinct NPC subcomplexes. The combination of well-characterized antibodies with
      different EM specimen preparation methods has allowed localization of several of
      these proteins within the three-dimensional (3-D) architecture of the NPC. Thus,
      the molecular dissection of the NPC is definitely on its way to being elucidated.
      Here, we review these findings and discuss the emerging structural concepts.

PMID- 8740527
TI  - Left ventricular perimysial collagen fibers uncoil rather than stretch during
      diastolic filling.
AB  - The collagen fibers in the myocardium are initially wavy, suggesting that they
      may not be directly stretched for a portion of diastolic filling. To test whether
      the fibers gradually straighten and at what left ventricular (LV) pressure they
      become straight, 24 isolated, arrested rat hearts were fixed at physiologic
      diastolic LV pressures and changes in collagen structure were examined. As LV
      pressure increased, mean ( +/- SE) sarcomere length increased (1.80 +/- 0.02 to
      1.88 +/- 0.02 from 0 mmHg to 26.3 +/- 4.1 mmHg) while the tortuosity of the
      perimysial fibers (fiber length/midline length) decreased (1.088 +/- 0.014 to
      1.031 +/- 0.006 from 0 mmHg to 26.3 +/- 4.1 mmHg). Transmural variations in
      collagen structure paralleled the trends in sarcomere length (epicardial regions
      had longer sarcomeres and straighter collagen fibers than endocardial regions).
      These results indicate that there is a tight coupling between perimysial collagen
      fibers and myocytes, consistent with the nonlinear pressure-volume and pressure
      sarcomere length relationships.

PMID- 8740528
TI  - Mechanical restitution and recirculation fraction in cardiac myocytes and left
      ventricular muscle of adult rats.
AB  - Unloaded cell shortening was measured in electrically stimulated myocytes from
      adult rat hearts to compare the contractile response to stimulation with that in
      isometrically contracting left ventricular papillary muscles under similar
      experimental conditions, but preloaded to produce maximum twitch tension.
      Mechanical restitution in cells followed a biexponential function with time
      constants of 0.19 +/- 0.03 s and 36.4 +/- 10.2 s (7 cells from 5 hearts, n =
      7/5). The time constants for papillary muscles were 0.58 +/- 0.05 s and 14.6 +/-
      1.0 s (n = 6/6). In myocytes, maximum post-rest potentiation occurred after 30 to
      60 s of rest. The potentiation after 60 s of rest was 2.48 +/- 0.31 times the
      steadystate in cells and 2.63 +/- 0.16 in papillary muscles. Recirculation
      fraction of C2+ as calculated from the decay of post-rest potentiation was 0.84
      +/- 0.04 in single cells and 0.59 +/- 0.02 in papillary muscles (p < 0.005).
      Caffeine (3mM) abolished post-rest potentiation in both types of preparations.
      The numerical values for the time constants of mechanical restitution,
      potentiation factor and recirculation fraction in papillary muscles did not
      depend on preload. It is concluded that interval-dependent changes of
      contractility are preserved in single cardiac cells but the kinetics of decay of
      potentiation appear to have changed quantitatively.

PMID- 8740529
TI  - Effects of a sinus node inhibitor on the normal and failing rabbit heart.
AB  - The effects on cardiac function of slowed frequency produced by a sinus node
      inhibitor (zatebradine, or UL-FS 49) were studied in the conscious rabbit under
      control conditions (n = 16) and after heart failure was produced by rapid atrial
      pacing for an average of 18.5 days (n = 8). Echocardiography was used to verify
      severe left ventricular (LV) dysfunction, and high-fidelity micromanometry and
      cardiac output measurements (Doppler echo) were performed. Echocardiographic
      fractional shortening was 40.3 +/- 4.1 % (SD) in controls; in heart failure it
      was 18.0 +/- 1.6 %, and the LV was enlarged. In controls, as heart rate (HR) was
      decreased from 279 beats per minute (bpm) by incremental doses of zatebradine (up
      to 0.75 mg/kg), maximal changes occurred when the heart reached 218 bpm with a
      maximum decrease of the first derivative of LV pressure (LV dP/dtmax) of 15.9 %;
      LV enddiastolic pressure (EDP) increased from 4.3 to 8.4 mmHg along with a
      significant decrease in cardiac index (CI) of 15.2 %, while LV systolic pressure
      (SP) was stable. In heart failure, LV dP/dtmax and CI were markedly reduced
      compared to controls and with reduction of HR from 257 to 221 bpm LV dP/dtmax was
      unchanged, LVEDP increased slightly (NS), LVSP was unchanged and CI fell by 13.5
      % at the highest dose. In subgroups (control n = 9, failure n = 6), in order to
      eliminate the hemodynamic effects of cardiac slowing by zatebradine the sinus
      rate present before zatebradine was matched by atrial pacing; this procedure
      eliminated all hemodynamic abnormalities accompanying cardiac slowing in both
      groups. In conclusion, slowed HR due to a sinus node inhibitor was well tolerated
      in severe heart failure, and all negative hemodynamic responses in both controls
      and in heart failure were due entirely to a negative forcefrequency effect,
      without a direct depressant action of zatebradine on the myocardium.

PMID- 8740530
TI  - Ischemic event characteristics determine the extent of myocardial stunning in
      conscious dogs.
AB  - Both the severity and duration of postischemic myocardial dysfunction ("stunned"
      myocardium) are unpredictable and may vary considerably between subjects that
      underwent apparently similar ischemic insults. To explain this heterogeneous
      response of the heart to ischemia and reperfusion, we investigated the
      determinants of stunning in conscious dogs. Twenty-five dogs were chronically
      instrumented for measurement of global and regional myocardial performance (wall
      thickening) and myocardial perfusion (coloured microspheres). A hydraulic
      occluder was positioned around the LAD coronary artery. Conscious dogs were
      subjected to acute coronary artery occlusions of predetermined duration (2, 5 and
      10 min), followed by complete reperfusion. Multiple regression analysis
      identified the following variables as determinants of postischemic contractile
      recovery: 1) the duration of ischemia (p < 0.01),2) the amount of collateral
      perfusion (p = 0.01) and 3) left ventricular end-diastolic pressure during
      ischemia (p < 0.01). Neither the severity of regional dyskinesia during ischemia
      nor indices of global systolic hemodynamic performance correlated with the rate
      of recovery. Our data confirm that myocardial stunning relates primarily to the
      intensity of preceding ischemia. Variations in the preexisting level of
      collateral perfusion may result in markedly different recovery profiles. Except
      for LV end-diastolic pressure during ischemia, indices of global and regional
      cardiac performance fail to predict the severity of postischemic contractile
      failure.

PMID- 8740531
TI  - Hemodynamic correlates of baroreflex impairment of heart rate in experimental
      canine heart failure.
AB  - The arterial baroreflex has been shown to be depressed in both clinical and
      experimental heart failure. The mechanism and significance of this depression
      remains controversial. Part of the change may reside in the baroreceptor as well
      as in the target organ. Previous studies in this laboratory have shown that there
      is no central depression of the baroreflex in anesthetized dogs. The present
      study was undertaken to determine the relationship between the change in
      baroreflex sensitivity (BRS) and the impairment of various hemodynamic parameters
      during the development of chronic heart failure in conscious dogs (n = 15). The
      animals were instrumented to record pressures and derivatives in the left atrium,
      aorta and the left ventricle. Heart failure was achieved by rapid left
      ventricular pacing (250 bpm) until the development of clinical signs. BRS was
      determined by correlating systolic arterial blood pressure and pulse interval
      during bolus injections of nitroglycerin and phenylephrine. Data were analyzed by
      correlating the changes in BRS (n = 90) with respect to changes in each
      parameter. No or a weak correlation was found between the changes in the
      baroreflex and parameters of systolic function or time of pacing. A stronger
      correlation was found between BRS and parameters of preload such as left
      ventricular enddiastolic pressure and left atrial pressure (p < 0.001). In
      general, the bradycardia responses were depressed less than the tachycardia
      responses. The correlation between BRS and left atrial or left ventricular end
      diastolic pressure is consistent with the view that augmented input from cardiac
      receptors may contribute to the depressed baroreflex function in heart failure.
      These data also suggest that the sympathetic limb of baroreflex control of heart
      rate in chronic heart failure is depressed earlier and to a greater extent then
      the vagal limb.

PMID- 8740533
TI  - Inhalation experiments with mixtures of hydrocarbons. Experimental design,
      statistics and interpretation of kinetics and possible interactions.
AB  - The paper describes experimental and statistical methods for toxicokinetic
      evaluation of mixtures in inhalation experiments. Synthetic mixtures of three C9
      n-paraffinic, naphthenic and aromatic hydrocarbons (n-nonane,
      trimethylcyclohexane and trimethylbenzene, respectively) were studied in the rat
      after inhalation for 12h. The hydrocarbons were mixed according to principles for
      statistical experimental design using mixture design at four vapour levels (75,
      150, 300 and 450 ppm) to support an empirical model with linear, interaction and
      quadratic terms (Taylor polynome). Immediately after exposure, concentrations of
      hydrocarbons were measured by head space gas chromatography in blood, brain,
      liver, kidneys and perirenal fat. Multivariate data analysis and modelling were
      performed with PLS (projections to latent structures). The best models were
      obtained after removing all interaction terms, suggesting that there were no
      interactions between the hydrocarbons with respect to absorption and
      distribution. Uptake of paraffins and particularly aromatics is best described by
      quadratic models, whereas the uptake of the naphthenic hydrocarbons is nearly
      linear. All models are good, with high correlation (r2) and prediction properties
      (Q2), the latter after cross validation. The concentrations of aromates in blood
      were high compared to the other hydrocarbons. At concentrations below 250 ppm,
      the naphthene reached higher concentrations in the brain compared to the paraffin
      and the aromate. Statistical experimental design, multivariate data analysis and
      modelling have proved useful for the evaluation of synthetic mixtures. The
      principles may also be used in the design of liquid mixtures, which may be
      evaporated partially or completely.

PMID- 8740534
TI  - Comparison of the influence of binary mixtures versus a ternary mixture of
      inhaled aromatic hydrocarbons on their blood kinetics in the rat.
AB  - The objective of the present study was to compare the influence of various binary
      mixtures containing ethylbenzene (EBZ), toluene (TOL) or xylene (XYL)
      administered by inhalation, with the influence exerted by a ternary mixture, on
      the kinetics of these solvents in blood. Groups of four rats were exposed for 4 h
      to TOL, XYL and EBZ, singly or in combination. The concentration of TOL, XYL and
      EBZ in blood was measured at various times (5, 30, 60, 90 and 120 min) following
      the end of exposure and the areas under the blood concentration curves (AUC) were
      calculated. Results showed that exposures to binary and ternary mixtures resulted
      in significantly higher (P < 0.05) blood concentrations of unchanged solvents as
      a result of metabolic interaction between these solvents. When the comparison was
      based on individual solvents, there was no difference between effect exerted by
      the ternary mixture and the binary mixtures, except for one. However, a
      comparison based on the total concentration of unchanged solvents disclosed that
      exposure to the ternary mixture resulted in greater interactive effects (3.17
      fold increase) than exposures to binary mixtures (1.97-fold increase), whereas
      four out of six binary mixtures produced higher total levels of unchanged
      solvents in blood compared to the ternary mixture. This study shows that the
      greater risk of toxicity often thought to be associated with exposures to complex
      mixtures should not only be related to the magnitude of interactive effects among
      components (i.e., degree of mutual metabolic interaction) resulting from combined
      exposures, but also should take into account, as is universally recognized, the
      internal total dose of toxic chemicals in target organs/tissues.

PMID- 8740532
TI  - Glossary: methods for the measurement of coronary blood flow and myocardial
      perfusion.

PMID- 8740535
TI  - Evaluation of cross-sensitization among dye-intermediate agents using a modified
      lymphocyte transformation test.
AB  - We evaluated cross-sensitization between p-phenylenediamine (pPDA) and p
      aminophenol (pAP) or m-phenylenediamine (mPDA) by a modified lymphocyte
      transformation test. Guinea pigs were sensitized with pPDA using the maximization
      test procedure. Lymph node cells from the animals were then cultured with pPDA,
      pAP or mPDA in the presence or absence of epidermal cells (EC). Transformed
      lymphocyte counts were evaluated by means of 3H-thymidine uptake. Non-sensitized
      guinea pigs were used as controls. Blastogenesis in lymphocytes from sensitized
      guinea pigs was enhanced when cultured with pPDA, pAP or mPDA in the absence or
      presence of EC than without the sensitizers, and the extent of response depended
      on the concentration of pPDA, pAP or mPDA added to the cultures. Blastogenesis in
      lymphocytes from control animals was not significantly enhanced in response to
      pPDA, pAP or mPDA in the presence or absence of EC. The extent of the response to
      pPDA was greater than that to pAP, which in turn was greater than that to mPDA.
      In contrast, because pPDA, pAP and mPDA are color developing agents, cross
      sensitization between pPDA and pAP or mPDA could not be evaluated by the results
      of an in vivo challenge due to pigmentation in the patch application sites. The
      results suggested that there is cross-sensitization between pPDA and pAP or mPDA,
      and that the modified lymphocyte transformation test is a useful predictive means
      of detecting cross-sensitization among chemicals, especially for color developing
      agents.

PMID- 8740536
TI  - Influence of fluoride on secretory pathway of the secretory ameloblast in rat
      incisor tooth germs exposed to sodium fluoride.
AB  - Fluoride, which is an environmental toxicant, is a potent inducer of mottled
      enamel in humans and rats. To define the influence of fluoride on the secretory
      pathway in enamel fluorosis, mottled enamel was induced in the incisor tooth
      germs of rats by subcutaneous injections of sodium fluoride for 4 days, and then
      morphological and cytochemical changes of the secretory ameloblast were examined
      in the tooth germs with HRP-labeled lectin (Con A, GS-I, SBA and PNA) and En3
      antibody labeling amelogenins. The accumulation of small vesicles on the route of
      the secretory pathway between the rER and the Golgi apparatus, disorder of Golgi
      stacks, and formation of abnormal large granules in distal cytoplasm were seen in
      the secretory ameloblast. Lectin staining patterns of the secretory ameloblast
      indicated the disturbance of the vesicular transport between the rER and the
      Golgi apparatus, and disorganization of the Golgi stack. Immunolabeling of the
      cell showed disruption of the sorting and fusion process on the secretory
      pathway. These results suggest that the fluoride disturbs the intracellular
      transport in the synthesis-secretory pathway of the ameloblast, and that this
      effect of fluoride on the synthesis-secretory pathway participates in the
      formation of enamel fluorosis.

PMID- 8740537
TI  - Reduced probability of orthodromically evoked action potential firing in CA1
      pyramidal cells of guinea pig hippocampal slices after acute thallium exposure.
AB  - We investigated the effect of thallium ions on extracellular field potentials in
      the CA1 region of guinea pig hippocampal slices in a matched-pair experimental
      setup. Somatic and dendritic responses evoked by paired-pulse stimulation of the
      Schaffer collateral-commissural pathway were recorded before, during and after
      acute thallium exposure and compared to field potentials from nontreated control
      slices recorded simultaneously. Thallium reduced the orthodromically evoked
      population spike reversibly in a clear concentration-effect relationship. In
      contrast, the field excitatory postsynaptic potential fEPSP, as well as the
      presynaptic fiber volley of the afferent pathway, were not affected by thallium.
      Furthermore, the paired-pulse facilitation was reversibly reduced during thallium
      exposure. Input-output relations clearly demonstrated that thallium did not
      interfere with the presynaptic transmitter release mechanisms or the postsynaptic
      transmitter receptor sensitivity, but had a predominant postsynaptic target site.
      Additionally, any influence of thallium ions on the somatic and/or axonal
      membrane excitability could be excluded, as the antidromically evoked responses
      after alvear stimulation were not diminished by thallium. Therefore, the main
      effect of thallium was a decoupling of the somatic from the dendritic activity at
      the CA1 pyramidal cells. We conclude that the toxic influence of thallium ions in
      the guinea pig hippocampus must be confined to intracellular somatic mechanisms.
      Interactions with intracellular organelles and an impairment of their calcium
      storage capacity are supposed.

PMID- 8740538
TI  - Determination of DSP toxins: comparative study of HPLC and bioassay to reduce the
      observation time of the mouse bioassay.
AB  - The progressive increase of DSP toxic episodes in shellfish in the last few years
      has generated a series of criticisms centered on the suitability of the mouse
      bioassay as a reference method to regulate the harvest of mussels from the growth
      area. The observation time in injected mice is currently fixed in 12 h by the
      actual Spanish rules. The revision of this time period and the lack of a
      established DSP toxin threshold which permits the commercialization of mussels
      contaminated under certain levels, are some of the actual demands from the
      industry. In this study, the results obtained in a comparative study of DSP toxic
      mussels are shown using the HPLC method and the mouse bioassay. Based on these
      results, we consider feasible the reduction to 5 h of the observation times of
      the mouse bioassay currently established in the actual legislation, as well as
      the establishment of a DSP-toxin threshold of 2 micrograms okadaic acid/g
      hepatopancreas, which regulates the possibility of harvesting and
      commercialization of contaminated mussels.

PMID- 8740539
TI  - Interaction of organophosphorus compounds with carboxylesterases in the rat.
AB  - Carboxylesterases (CarbE) are involved in detoxication of organophosphorus
      compounds (OPC) through two mechanisms: hydrolysis of ester bonds in OPC which
      contain them and binding of OPC at the active site of CarbE which reduces the
      amount of OPC available for acetylcholinesterase inhibition. This study of the
      interaction of rat plasma and liver CarbE with dichlorvos, soman and sarin in
      vitro and in vivo was undertaken in order to contribute to better understanding
      of the role of CarbE in detoxication of OPC. The results obtained have shown that
      inhibitory potency (I50) of dichlorvos, sarin and soman towards rat liver CarbE
      was 0.2 microM, 0.5 microM and 4.5 microM, respectively, for 20-min incubation at
      25 degrees C. Second-order rate constants (k(a)) for liver CarbE inhibition were
      2.3 x 10(5) M-1 min-1, 6.9 x 10(4) M-1 min-1 and 1.1 x 10(4) M-1 min-1 for
      dichlorvos, sarin and soman, respectively. The corresponding values for plasma
      CarbE could not be calculated because of dominant spontaneous reactivation of
      inhibited CarbE. CarbE inhibited with these OPC in vitro spontaneously reactivate
      with half-times of 18, 143 and 497 min for sarin, dichlorvos and soman in plasma
      and 111, 163 and 297 min for sarin, soman and dichlorvos in liver, respectively.
      These results were also confirmed in experiments in vivo in which rats were
      subcutaneously treated with 0.5 LD50 of these agents. The half-times of
      spontaneous reactivation of rat plasma CarbE in vivo were 1.2, 2.0 and 2.7 h for
      dichlorvos, sarin and soman, respectively. These findings have changed current
      understanding of the mechanism of interaction of CarbE with OPC and involvement
      of the enzymes in detoxication of OPC, suggesting an active and important role of
      the enzymes in metabolic conversions of OPC to their less toxic metabolites.

PMID- 8740540
TI  - Testosterone hydroxylase in evaluating induction and suppression of murine CYP
      isoenzymes by fenarimol.
AB  - This study aimed to investigate the effect of single and repeated administration
      of fenarimol on murine liver, kidney and lung microsomal CYP-catalyzed drug
      metabolism. The modulation of the regio- and stereo-selective hydroxylation of
      testosterone by fenarimol was considered in evaluating cocarcinogenic properties.
      Induction or suppression of different CYPs was recorded after a single dose of
      the fungicide. For example, in liver, 6 beta-(mainly associated with CYP3A), 7
      alpha- and 2 beta-testosterone hydroxylase (TH) activities were induced up to 4.8
      fold (7 alpha-TH) in female mice, at a dose of 150 mg/kg. In contrast, at 150 and
      300 mg/kg, 16 alpha-TH (CYP2B9), 17-TH (female) and 6 alpha-TH (CYP2A1 and 2B1,
      male) activities were appreciably reduced. In extrahepatic tissues, the CYP
      modulation pattern was different, 16 alpha-TH being the only metabolite decreased
      (lung, male). In kidney, 16 beta-TH and 17-TH activities were increased up to 5.8
      fold in female mice (lowest dose), while in lung 6 alpha-TH and 7 alpha-TH
      activities were induced up to 6- and 7-fold, respectively (both doses). Repeated
      treatment (150 mg/kg for 3 days) was able markedly to induce all steroid
      hydroxylations, up to 78-fold in 2 alpha-TH activity (male liver). In conclusion,
      fenarimol has a complex pattern of CYP induction or suppression in various
      tissues of both sexes, suggesting the possible toxic, cotoxic/cocarcinogenic and
      promoting potential of this fungicide.

PMID- 8740541
TI  - Oxidative DNA lesions in V79 cells mediated by pentachlorophenol metabolites.
AB  - Incubation of the pentachlorophenol (PCP) metabolites, tetrachloro-p-benzoquinone
      (chloranil, TCpBQ), tetrachloro-p-hydroquinone (TCpHQ) and tetrachloro-p
      benzoquinone (TCoBQ) with V79 Chinese hamster cells led to a significant
      enhancement of the amount of 8-hydroxydeoxyguanosine (8-OH-dG) in DNA. With PCP
      itself and the metabolite tetrachloro-o-hydroquinone (TCoHQ) no distinct
      induction of this lesion could be observed. The average yields of 8-OH-dG were
      about 2-2.5 times above background levels. In addition, TCpBQ and TCpHQ were able
      to generate DNA single-strand breaks, while PCP, TCoHQ and TCoBQ failed to induce
      this lesion. All incubations were performed for 1 h without exogenous metabolic
      activation and concentrations were 25 microM of the respective agent. It is
      concluded that these metabolites may contribute to the carcinogenicity of PCP
      observed in mice, by generating reactive oxygen species (ROS) through their redox
      cycling properties.

PMID- 8740542
TI  - An ultrastructure study of the in vitro effects of L-leucine methyl ester and
      ammonium chloride on Trypanosoma cruzi epimastigotes.
AB  - Trypanosoma cruzi epimastigotes were subjected to the lysosomotropic agents L
      leucine methyl ester and ammonium chloride to determine their effects on the
      ultrastructure of the parasite. The lysosomotropic agents applied to
      epimastigotes caused a time-dependent alteration in the morphology of the cells
      marked by a 5-fold increase in the number of lysosomes. Continued exposure to
      ammonium chloride caused slight disruption of the reservosomes. The amino acid
      ester, however, while causing the parasite to swell after prolonged exposure
      (e.g., 24 h), had little effect on the reservosomes, the kinetoplast, or even the
      mitochondrion. A specific inhibitor of cysteine proteinases provided some
      protection for lysosomes from the effects of the amino acid ester. Although it is
      agreed that reservosomes are similar to endosomes, no lysosomal fusion with the
      reservosomes was observed. Acid phosphatase activity was observed only in
      lysosomes.

PMID- 8740543
TI  - Parasite vaccine development: large-scale recovery of immunogenic Taenia ovis
      fusion protein GST-45W(B/X) from Escherichia coli inclusion bodies.
AB  - Genetically modified Escherichia coli expressing the Taenia ovis fusion protein
      GST-45W(B/X) as inclusion bodies were grown in volumes ranging up to 1000 l.
      Bacteria were inactivated by heat or chemical treatment without affecting
      immunogenicity. The fusion protein was recovered in a highly immunogenic form
      from washed inclusion bodies and from urea-solubilised inclusion bodies. The
      fusion protein was found to be stable in solution after storage at 4 degrees C
      for up to 2 years. Vaccines formulated with fusion protein from urea-soluble
      inclusion bodies gave consistently high protection (89-100%) against challenge
      infection. The methods described enabled the production of sufficient vaccine for
      large field trials. These trials generated the data required for product
      registration and manufacture of a vaccine to prevent T. ovis infection in sheep.

PMID- 8740544
TI  - Immunity to Plasmodium berghei exoerythrocytic forms derived from irradiated
      sporozoites.
AB  - The nature of immunity generated by Plasmodium berghei exoerythrocytic (EE)
      stages developing from irradiated sporozoites was studied using in vivo
      parameters of host protection on immunization with irradiated sporozoites and in
      vitro parameters of inhibition of sporozoite invasion and EE form development by
      serum antibodies from immunized mice. On in vivo challenge of immunized mice by
      sporozoites, protection was observed in an irradiation-dose-dependent manner.
      This finding stresses that protection is dependent on the irradiation dose of
      sporozoites that allows sporozoite penetration yet controls EE form development
      within the liver. Using the human hepatoma line Hep G2 as host cells in vitro, we
      observed that serum antibodies raised in mice immunized with irradiated
      sporozoites reacted with sporozoite- and hepatic-stage parasites in an
      immunofluorescent antibody test (IFAT). No reactivity was observed with blood
      stage parasites. Serum antibodies from mice immunized with 6- to 18-krad
      irradiated sporozoites inhibited sporozoite invasion and caused severe inhibition
      of EE form development in hepatoma cells, pointing to the antigenic content of EE
      forms developing from irradiated sporozoites (irra EE forms) as critical
      immunogens. Moreover, in an enzyme-linked immunosorbent assay (ELISA), serum
      antibodies raised to 12-krad-irradiated sporozoites showed reactivity to
      synthetic peptides representing the conserved Region II sequences of the P.
      falciparum circumsporozoite (CS) protein as well as the P. falciparum liver-stage
      specific antigen (LSA-1)-based repeat sequences, thus implicating an important
      role for both the sporozoite and the hepatic stage in protection.

PMID- 8740545
TI  - The length of strongylid nematode infective larvae as a reflection of
      developmental conditions in faeces and consequences on their viability.
AB  - Isolates from eight gastro-intestinal nematode species of sheep, cattle and deer
      parasites were maintained in sheep and faecal cultures were processed at
      different temperatures (for four species) and moistures (for the eight species).
      For all the tested species, the third-stage larvae (L3) were longer at
      temperatures optimal for development and their length increased linearly with
      faecal moisture contents (FMC). These variations in length mainly concerned the
      volume of intestinal cells. The length of L3 had no consequence on their survival
      in water at room temperature (five species tested), but the short L3 migrated
      more slowly on agar gel than did the longer ones (verified for three species) and
      exsheathed more slowly (verified for two species). The establishment rate
      observed for short L3 of Teladorsagia circumcincta in lambs was lower than that
      seen for long L3 in three other lambs, but the developed worms were similar in
      length and fecundity. These results are relevant to our understanding of how the
      different species could adapt to and/or compensate for adverse conditions of
      development.

PMID- 8740546
TI  - Ultrastructure of the gut caecal epithelium of Pricea multae (Monogenea:
      Polyopisthocotylea).
AB  - Ultrastructural observations of the gut caecal epithelium of Pricea multae
      revealed the presence of pigmented and non-pigmented digestive cells. The
      pigmented digestive cells were separated by a connecting syncytium and appeared
      elongated, with numerous vesicles appearing toward the apical cell surface. They
      were characterised by granular inclusions in the form of electron-dense pigments,
      which were eliminated by exocytosis. These cells and their lamellar connecting
      syncytium were observed projecting into the gut lumen. Transverse sections of the
      gut epithelium revealed intact portions of digestive cells lying in the lumen.
      Endocytosis at the apical surface of the pigmented digestive cells gave rise to
      the formation of granular inclusions, which appeared as electron-dense pigments
      confined to lysosomal vesicles within the digestive system. Electron X-ray
      microanalysis indicated these granules were primarily composed of iron,
      demonstrating that P. multae is a blood-feeder. The connecting syncytium, while
      probably involved in a structural, supportive role, may additionally function in
      the absorption of micromolecular nutrients from the host blood meal.

PMID- 8740547
TI  - Larval anisakids (Nematoda:Ascaridoidea) in horse mackerel (Trachurus trachurus)
      from the fish market in Granada, Spain.
AB  - Horse mackerel (Trachurus trachurus) from the fish market in Granada, southern
      Spain, were surveyed for anisakid nematodes. The fish came from fishing ports all
      over the country. Larval anisakids were found in 39.4% of the fish examined;
      26.1% were infected with third-stage larvae (L3s) of Anisakis simplex; 0.3%, with
      A. physeteris L3s; 31.1%, with Hysterothylacium aduncum L3s; and 1.7%, with
      fourth-stage larvae (L4s) of Hysterothylacium sp. Horse mackerel from
      Mediterranean Sea coastal ports (South and South-east Spain) had the lowest
      levels of infection, and those from Cantabrian Sea coastal ports (North Spain)
      had the highest. The variation in infection levels with host size (age) and
      season of capture are surveyed.

PMID- 8740548
TI  - Light microscopic description of Eimeria sparis sp. nov. and Goussia sparis sp.
      nov. (Protozoa:Apicomplexa) from Sparus aurata L. (Pisces: Teleostei).
AB  - Two new species of Coccidia, Eimeria sparis sp. nov. and Goussia sparis sp. nov.,
      were found in the intestine of Sparus aurata from different culture systems of
      Spain. These are the first coccidian species described from this host. E. sparis
      is distinguished from other Eimeria spp. from Perciformes in the size and shape
      of the sporocysts, which measure 6-9.7 (mean = 7.78, SD = 1.33) x4-6.5 (5.3 +/-
      0.92) microns, and in the Stieda-like body. Mature oocysts, spherical or
      subspherical, measure 9.4-14.3 (11.88 +/- 1.85) microns. G. sparis differs from
      other Goussia spp. from fish of the Mediterranean area in the size and shape of
      the oocysts and sporocysts as well as in the location. Mature oocysts measure 16
      21 (17.4 +/- 1.5) x 13-18 (14.4 +/- 1.7) microns and sporocysts, 8.6-10.3 (9.5 +/
      0.5) x 5.7-7.4 (mean 6.5 +/- 0.5) microns. The different stages of merogony,
      gamogony, and sporogony of both species were examined at the light-microscope
      level in fresh material and histology specimens. Sporulation was endogenous in E.
      sparis and exogenous in G. sparis.

PMID- 8740549
TI  - Fasciola hepatica: disruption of the vitelline cells in vitro by the sulphoxide
      metabolite of triclabendazole.
AB  - The effects of the active sulphoxide metabolite of the fasciolicide
      triclabendazole (Fasinex, Ciba-Geigy) on the vitelline cells of Fasciola hepatica
      were determined in vitro by transmission electron microscopy using both intact
      flukes and tissue-slice material. At a triclabendazole concentration of 15
      micrograms/ml the vitelline cells of intact flukes showed ultrastructural changes
      only after prolonged incubation periods (12-24 h). The changes observed were a
      swelling of the granular endoplasmic reticulum (GER) cisternae with decreased
      ribosomal covering in the intermediate-type cells and condensation of chromatin
      and disappearance of the nucleolus in the nucleus of the stem cell. Similar
      changes were evident more quickly (by 6 h) in whole flukes treated at the higher
      concentration of 50 micrograms/ml. The shell globule clusters were loosely packed
      in the intermediate type-2 cells, and the number of intermediate type-1 cells
      declined with more prolonged incubation. Disruption of the nurse-cell cytoplasm
      was also observed from 12 h onwards. After only 6 h incubation of tissue-slice
      material at 50 micrograms/ml, intermediate type-1 cells were absent, shell
      globule clusters in mature cells were loosely packed and the nurse-cell cytoplasm
      was badly disrupted. By 12 h the vitelline cells were vacuolated and grossly
      abnormal. The results are discussed in relation to postulated actions of
      triclabendazole against the microtubule component of the cytoskeleton and against
      protein synthesis in the fluke.

PMID- 8740550
TI  - Toxoplasma gondii: appearance of specific markers during the development of
      tissue cysts in vitro.
AB  - Cultures were initiated in Madin-Darby bovine kidney (MDBK) cells from ME49
      strain bradyzoites. Specific antibody staining showed that two populations of
      parasites exist, one being a predominant population of tachyzoites that were
      positive for the tachyzoite-specific marker SAG1 and negative for the bradyzoite
      specific marker P36. All of these parasites expressed the dense granule molecule
      GRA5, which in larger clusters was seen faintly in the membrane of the
      parasitophorous vacuole. No rosette formation or monolayer destruction was
      observed. Also seen was a sub-population of bradyzoites that were positive for
      P36 and negative for SAG1. Approximately 90% of these parasites expressed the
      matrix molecule P29. These parasites were also positive for the dense granule
      molecule GRA5, which was highly concentrated in the wall of the cyst. These
      bradyzoite clusters contained fewer parasites and were smaller in diameter than
      those expressing tachyzoite markers.

PMID- 8740551
TI  - Eimeria coecicola Cheissin 1947: endogenous development in gut-associated
      lymphoid tissue.
AB  - Coccidia-free rabbits were inoculated with different doses of a pure strain of
      Eimeria coecicola and samples of gut were taken at 80, 96, 112, 128, 144, and 160
      h postinoculation. The use of a very low infective dose (2-20 oocysts) was
      sufficient to study the last merogony. The number of merozoites in meronts
      increased when the infective dose decreased. Only the first merogony of this
      coccidium in lymphocytes or M-cells of gut-associated lymphoid tissue (GALT) has
      previously been described. Three other generations of meronts are described
      herein. All these endogenous stages were observed in the epithelium of the
      vermiform appendix, sacculus rotundus, and Peyer's patches, especially at the
      bases of the domes. However, in heavily infected tissues the gamonts were seen
      throughout the epithelium of the GALT. The third- and fourth-generation meronts
      were of two types. As in other eimerian species of the rabbit, type A meronts
      produced thick polynucleated merozoites, whereas type B meronts gave rise to
      large numbers of thin merozoites with one nucleus. Microgamonts were
      polynucleated and less numerous than macrogamonts. Type A meronts were also
      polynucleated and less numerous at the end of the merogony. Therefore, types A
      and B could correspond to a sexual phenotype differentiation occuring during the
      two asexual phases of multiplication.

PMID- 8740552
TI  - Analysis of roles of natural killer cells in defense against Plasmodium chabaudi
      in mice.
AB  - Mice that have recovered from a primary infection with Plasmodium chabaudi have
      been shown to resist a secondary infection. In the present study the authors
      investigated how natural killer (NK) cells were involved in this resistance.
      Spleen cells from P. chabaudiprimed C57BL/6 mice could transfer protection
      against P. chabaudi infection into naive syngeneic mice, but spleen cells from
      unprimed mice could not. T-enriched cells purified from primed spleen cells could
      also transfer such protection. Transfer of NK cells from primed spleen cells
      failed to protect against challenge infection. However, depletion of NK cells in
      host mice by injection of an anti-NK1.1 monoclonal antibody resulted in higher
      mortality relative to controls. The possible protective roles of NK cells in P.
      chabaudi infection are discussed.

PMID- 8740553
TI  - Flow-cytometry analysis of sheep-nematode egg populations.
AB  - Flow cytometry was applied to the analysis of nematode populations. Three strains
      of Haemonchus contortus susceptible or resistant to anthelmintics were studied.
      Eggs were chosen for these analyses. Data on light-scatter emissions and native
      green fluorescence were collected. In addition, the size of the eggs (image
      analysis), the hatching rate, and the susceptibility to benzimidazoles were
      measured. The results showed that nematode eggs are a suitable material for
      multiparametric flow-cytometry analyses. Forward-scatter emission is a
      discriminating parameter for the egg size. The hatching rate and side-scatter
      emission have a significantly positive relationship. For resistant strains, the
      rate of resistance shows a significant regression on the native greenfluorescence
      pulses that might reflect the state of oxidation of associated flavin molecules.

PMID- 8740554
TI  - Growth and fecundity of Oesophagostomum dentatum in high-level infections and
      after transplantation into naive pigs.
AB  - This experiment was designed to examine the growth, proportion of stages, and
      fecundity of an Oesophagostomum dentatum population by transplantation of a known
      small number of worms from a high-density population into helminth-naive
      recipient pigs. Approximately 1,500 4-week-old worms [69% fourth-stage larvae
      (L4), 31% adult worms] were transplanted into each of 5 recipient pigs (group B),
      and these pigs, along with a group of 5 high-level-infection control pigs (group
      C), were killed at 4 weeks after transplantation to determine and compare the
      worm burdens. By 2 weeks after transplantation and throughout the experiment,
      fecal egg counts of group B exceeded those of group C and the fecundity of the
      worms was higher, though not statistically significantly so, in the transplanted
      worms. In the recipient pigs, all worms (approx. 70% establishment) had developed
      to the adult stage and were significantly longer than worms recovered from the
      group C pigs.

PMID- 8740555
TI  - Characterization of the arylalkylamine N-acetyltransferase in Onchocerca
      volvulus.
AB  - The characteristics and kinetic properties of an arylalkylamine N
      acetyltransferase were studied in partially purified preparations of the human
      filarial parasite Onchocerca volvulus. The enzyme, which had a relative molecular
      mass (M(r)) of 37-38 kDa, catalyzed the acetylation of arylalkylamines but did
      not accept arylamines or polyamines as substrates. The optimal pH for enzyme
      activity was found to be 8.5 in TRIS-HCI. The apparent Michaelis constant (K(m))
      and maximum velocity (Vmax) determined from Lineweaver-Burk plots for tryptamine
      were 1.8 microM and 29 nmol min-1 mg protein-1, respectively. Except for the
      catecholamines, the other arylalkylamines such as 5-hydroxytryptamine (5-HT),
      tyramine, and octopamine similarly exhibited high affinities and reaction rates.
      Whereas the enzyme is inhibited by metals and p-chloro-mercuribenzoate, it is
      inactivated neither by amethopterin nor by cystamine and is thereby distinguished
      from the mammalian arylamine N-acetyltransferase. Like other N-acetyltransferases
      whose function is the regulation of intracellular amine levels, the enzyme may
      have a role in the inactivation of excess biogenic amine in this parasite.

PMID- 8740556
TI  - Inhibition of glutathione synthesis of Ascaris suum by buthionine sulfoximine.
AB  - We investigated the effect of DL-buthionine-S,R-sulfoximine (BSO), a selective
      glutathione (GSH)-depleting agent, on the GSH synthesis of Ascaris suum. The GSH
      concentrations of the reproductive and muscle tissues of A. suum were determined
      to be 8.5 +/- 0.3 and 14.3 +/- 1.3 (n = 3) nmol/mg protein, respectively. After
      treatment of the parasites with 10 microM BSO for 24 h, the GSH content of the
      reproductive tissue of A. suum was totally depleted as compared with that of
      untreated controls. However, the GSH levels of the muscle tissue were reduced to
      only 50% after treatment of the worms for 24 h with 10 microM BSO. Exogenous GSH
      had no significant effect on the GSH level of the parasites when the worms were
      incubated for 4 h in RPMI 1640 medium supplemented with 1 mM GSH. In the presence
      of exogenous GSH, BSO was less effective in depleting the GSH levels of the
      parasites, which may indicate that the parasites can replenish their GSH levels.
      GSH depletion, which has been discussed as being therapeutically effective when
      normal and tumor cells or parasites have markedly different requirements for GSH,
      may have applications in the development of drugs against nematode infections.

PMID- 8740557
TI  - Colony formation of Blastocystis hominis in soft agar.
AB  - This is the first description of a method for growing axenized Blastocystis
      hominis as colonies in petri dishes containing soft agar. Blastocystis cells
      cultured in two types of agar appeared to show different colonial morphologies as
      well as differing colony yields. Microscopic examination of the colonies revealed
      many amoeboid and giant cells. Many cells were also shown to possess thin
      filament-like structures that appeared to stretch across the central vacuole.

PMID- 8740558
TI  - Antigenic cross-reactivity in mice between third-stage larvae of Anisakis simplex
      and other nematodes.
AB  - We used ELISA and immunoblotting to investigate antigenic cross-reactivity in
      mice between third-stage larvae of Anisakis simplex and five other nematodes: the
      ascaridoids Ascaris suum, Toxocara canis and Hysterothylacium aduncum, and the
      nonascaridoids Trichinella spiralis and Trichuris muris. Two sera were raised
      against each species (including A. simplex, but excluding A. suum), by infection
      or by immunization with somatic antigens. Serum against A. suum was raised by
      immunization only. The reactivities of each serum with A. simplex somatic
      antigens (SA), excretion-secretion antigens (ES), pseudocoelomic fluid antigens
      (PF) and cuticular antigens (CA) were investigated. The results of ELISA
      indicated high antigenic cross-reactivity between A. simplex and the remaining
      ascaridoid nematodes, confirming that there is extensive antigenic similarity
      within this group of nematode parasites. Immunoblotting again confirmed the high
      degree of cross-reactivity between the SA of A. simplex and SAs of the other
      ascaridoids, although several A. simplex SA components in the 11-18 kDA range
      were only recognized by sera from mice infected with A. simplex. In addition, two
      A. simplex PF components of 22 and 27 kDA, were recognized only by sera from mice
      infected with, or immunized with the SA of, A. simplex. Finally, the anti
      phosphorylcholine monoclonal antibody BH8 recognized only a small number of A.
      simplex antigens, indicating that phosphorylcholine epitopes are not significant
      contributors to the observed cross-reactivity with the other nematodes.

PMID- 8740559
TI  - The sheath of the microfilaria of Brugia malayi from human infections has IgG on
      its surface.
AB  - Microfilariae (mf) of Brugia malayi from microfilaraemic people had human IgG on
      their sheath. Fluorescent antibody studies showed that the predominant IgG
      isotype was IgG3, with IgG4 and IgG1 being present in lower quantities. Human
      albumin could not be detected. The sera of patients with chronic disease
      contained high levels of an IgG2 antibody that reacted with the sheath of mf
      taken from other people.

PMID- 8740560
TI  - Targeting T cells for GVHD therapy.
AB  - Bone marrow transplantation is currently used to treat a variety of life
      threatening diseases. Its applications could be expanded if the risks of graft
      versus-host disease (GVHD), a complex pathologic disease, could be reduced.
      Immunotoxins may provide a means to control drug refractory GVHD. This article
      will discuss the development of immunotoxin approaches for either GVHD prevention
      or treatment, and explore their limitations.

PMID- 8740561
TI  - Immunotoxins for central nervous system malignancy.
AB  - Current therapy for primary brain tumors, metastatic brain tumors and
      leptomeningeal carcinomatosus is inadequate. Monoclonal antibodies and certain
      biological ligands such as transferrin and epidermal growth factor bind
      selectively to tumors but in and of themselves have little therapeutic activity.
      Linking these binding moieties to protein toxins yields new molecules, called
      immunotoxins, that display enormous cell-type specific toxicity in vitro and
      could be valuable agents for treatment of CNS cancer. This review discusses our
      development of immunotoxins to treat brain tumors after systemic, intrathecal and
      intratumoral injection.

PMID- 8740562
TI  - Targeting toxins to neural antigens and receptors.
AB  - Immunotoxins have been used to study the targeting of biologically active
      substances at neurons in vivo and to make experimental neural lesions. OX7
      saporin, directed against Thy 1, destroys any neuron. 192 IgG-saporin, directed
      against the 'low affinity' neurotrophin receptor (p 75NTR), selectively destroys
      neurons expressing this receptor (sympathetic, sensory, cholinergic basal
      forebrain, cerebellar Purkinje). Anti-D beta H-saporin, directed against dopamine
      beta-hydroxylase, the enzyme that converts dopamine to norepinephrine,
      selectively destroys noradrenergic neurons (sympathetic, CNS). These agents show
      that several types of neural antigens may prove useful in treating pain, and anti
      D beta H-saporin may be active against pheochromocytoma or neuroblastoma.

PMID- 8740563
TI  - The performance of e23(Fv)PEs, recombinant toxins targeting the erbB-2 protein.
AB  - The overexpression of the erbB-2 (HER-2, neu) gene has attracted significant
      interest as a molecular target for the rational design of cancer therapies. This
      review examines the design and preclinical testing phase for one such
      experimental therapy, recombinant toxins targeted to the erbB-2 protein, termed
      e23(Fv)PEs.

PMID- 8740564
TI  - Why toxins!
AB  - Toxins are potent cytotoxic proteins which gain access to the interior of
      mammalian cells by receptor-mediated endocytosis. However, the trafficking
      pathways within mammalian cells are complex and toxins must be processed to
      active forms while avoiding degradation by the lysosomal system. Once delivered
      to an appropriate intracellular location, the active toxin fragment translocates
      to the cell cytosol and inhibits protein synthesis. Chimeric toxins are
      constructed by removing the toxins natural binding domain and replacing it with
      an antibody or cell-binding ligand that redirects cell killing activity to cancer
      cells. Gaining an understanding of how toxins manoeuvre within cells is vital for
      improving the effectiveness of chimeric toxins.

PMID- 8740565
TI  - The CCL conferences revisited.
AB  - The history of the ten conferences on Computing in Clinical Laboratories (CCL)
      since the first one in Birmingham, UK, 1975, mirrors the developments in medical
      laboratory computing during nearly twenty years.

PMID- 8740566
TI  - The clinical interface--a British physician's view.
AB  - There appears to be a growing divergence, in the UK, between the hospital
      clinician and laboratory specialist as to their respective roles in the
      investigation of patients. The clinician requires a prompt service based on
      effective communication systems and rapid turnaround of test results. Laboratory
      specialists generally perceive both their role and that of the laboratory as
      consultative, often imposing barriers in order to give efficient patient care and
      maintain efficient use of resources. In order that greatest use of the laboratory
      service can be achieved in the United Kingdom, guidelines relating to appropriate
      and effective laboratory investigation should be agreed between clinicians and
      laboratory specialists and further studies undertaken to characterise the effects
      on outcome measures such as patient bed-stay, of the availability of test data
      and consultant opinion. The strong tradition of mutual respect and understanding
      between the two disciplines should not be jeopardised by the view of the
      clinician, who has the responsibility of diagnosing and managing the patient,
      that the laboratories are there to provide a service. Improved communication,
      both verbal and electronic, is required to reposition laboratory services within
      a rapidly changing health service.

PMID- 8740567
TI  - A new clinical laboratory information system architecture from the OpenLabs
      project offering advanced services for laboratory staff and users.
AB  - The OpenLabs project aims to improve the efficiency and effectiveness of clinical
      laboratory services by integrating decision support systems with laboratory
      information systems and equipment. Standards for electronic data interchange
      between laboratories and other medical systems using the EUCLIDES/OpenLabs coding
      scheme and an open architecture for clinical laboratory information systems have
      been specified. This article gives an account of the proposed architecture and
      outlines new software applications being developed using the architecture which
      provide advanced services for ordering and reporting of laboratory tests,
      advanced instrument workstation and laboratory management services, including an
      OpenLabs Service Manager application which co-ordinates the available services.

PMID- 8740568
TI  - Client/Server computing: is this the future direction for the clinical
      laboratory?
AB  - One of the major trends in computing for the 1990s is the move towards
      distributed systems based on Client/Server architecture. Although a recent survey
      has suggested that some 41% of the major companies in the UK are either using or
      planning to adopt this new technology, there is little evidence at present of
      similar progress in the field of clinical laboratory computing. The Pathology
      Laboratories at St. Luke's Hospital have been developing in-house computer
      systems using object-oriented software tools since 1988, but these were initially
      based on conventional file sharing and suffered from poor performance under load.
      The conversion to Client/Server took place in March 1993 and the results have
      either met or exceeded all expectations. Our experience suggests that this
      approach may well be the way forward for the high performance but user-friendly
      laboratory systems of the future.

PMID- 8740569
TI  - Automated technical validation--a real time expert system for decision support.
AB  - Dealing daily with various machines and various control specimens provides a lot
      of data that cannot be processed manually. In order to help decision-making we
      wrote specific software coping with the traditional QC, with patient data (mean
      of normals, delta check) and with criteria related to the analytical equipment
      (flags and alarms). Four machines (3 Ektachem 700 and 1 Hitachi 911) analysing 25
      common chemical tests are controlled. Every day, three different control
      specimens and one more once a week (regional survey) are run on the various
      pieces of equipment. The data are collected on a 486 microcomputer connected to
      the central computer. For every parameter the standard deviation is compared with
      the published acceptable limits and the Westgard's rules are computed. The mean
      of normals is continuously monitored. The final decision induces either an alarm
      sound and the print-out of the cause of rejection or, if no alarms happen, the
      daily print-out of recorded data, with or without the Levey Jennings graphs.

PMID- 8740570
TI  - The clinical workstation as a means of improving laboratory use.
AB  - Driven to make timely decisions, doctors may act with less than all of the
      relevant patient data. Sub-optimal use of clinical laboratory resources can
      result. Our clinicians' workstation (CWS) is meant to provide doctors and nurses
      ready access to laboratory results in a form that makes the data easy to review
      and use. In addition, the workstation provides immediate feedback regarding blood
      orders, to encourage appropriate clinical practice. Feedback is based on the
      medical staff's clinical guidelines that have been incorporated into an embedded
      expert system. CWS also helps blood bank physicians to monitor, review and
      control requests for special needs such as irradiated products. Challenges to
      system acceptance await those trying to bring functional decision support to the
      clinical environment. Among these are barriers to understanding and cooperation
      posed by departmental boundaries and interacting professional cultures as well as
      the politics of hospital-based information systems.

PMID- 8740571
TI  - Improvement of emergency and routine turnaround time by data processing and
      instrumentation changes.
AB  - A retrospective study of stat and routine laboratory analysis turnaround time was
      performed in a 1000-bed public hospital before and after the implementation of
      instrument and computer changes. Significant decreases in turnaround time were
      found for enzyme tests in the stat laboratory and for all analytes studied in the
      routine laboratory. The decrease in TAT was evaluated using a physician
      satisfaction scale, elaborated in conjunction with specialists from several
      fields, that disclosed an increase in perceptive quality. Results from other
      authors and recommendations by the College of American Pathologists for
      turnaround time are discussed.

PMID- 8740572
TI  - Neural networks and fuzzy logic in clinical laboratory computing with application
      to integrated monitoring.
AB  - We present an analysis of the computational features of neural networks and fuzzy
      logic architectures which attempts to explain their recent popularity as well as
      their drawbacks. Based upon many reports in several fields, we identify the key
      computational requirements in the clinical laboratory setting, and review several
      classical tools. In particular we make the observation that all of these needs
      may be viewed as a search for an appropriate mathematical mapping. We suggest
      that the neural networks promise as a universal function approximant is the main
      source of its apparent attractivity. We then describe a customized neural network
      architecture as a non-linear, adaptive signal processor for integrated
      monitoring. This architecture is employed in the Adaptive Real-Time
      Anesthesiologist Associate (ARTAA) system, which has been developed as a joint
      project at the Department of Anesthesiology, Albert Einstein Medical Center and
      the Electrical and Computer Engineering Department, Drexel University in
      Philadelphia, USA. In this application the neural network realizes a non-linear
      scalar map from the set of physiological signals to a vital function status (VFS)
      indicator. The system is now under clinical testing.

PMID- 8740573
TI  - Self-organizing neural networks--an alternative way of cluster analysis in
      clinical chemistry.
AB  - Supervised learning schemes have been employed by several workers for training
      neural networks designed to solve clinical problems. We demonstrate that
      unsupervised techniques can also produce interesting and meaningful results.
      Using a data set on the chemical composition of milk from 22 different mammals,
      we demonstrate that self-organizing feature maps (Kohonen networks) as well as a
      modified version of error backpropagation technique yield results mimicking
      conventional cluster analysis. Both techniques are able to project a potentially
      multi-dimensional input vector onto a two-dimensional space whereby neighborhood
      relationships remain conserved. Thus, these techniques can be used for reducing
      dimensionality of complicated data sets and for enhancing comprehensibility of
      features hidden in the data matrix.

PMID- 8740574
TI  - Introduction of a new laboratory test: an econometric approach with the use of
      neural network analysis.
AB  - We designed a simulation model for the assessment of the financial risks involved
      when a new diagnostic test is introduced in the laboratory. The model is based on
      a neural network consisting of ten neurons and assumes that input entities can
      have assigned appropriate uncertainty. Simulations are done on a 1-day interval
      basis. Risk analysis completes the model and the financial effects are evaluated
      for a selected time period. The basic output of the simulation consists of total
      expenses and income during the simulation time, net present value of the project
      at the end of simulation, total number of control samples during simulation,
      total number of patients evaluated and total number of used kits.

PMID- 8740575
TI  - Computer assisted interpretation of laboratory test data with 'MDI-LabLink'.
AB  - Physicians have to confront an enormous output of laboratory data. Normally, only
      a few experts manually perform the interpretation of highly specialised
      laboratory tests. PC Windows based 'MDI-LabLink' automates interpretation and
      expands traditional rule-based expert systems with flexibility and graphic
      illustrations of complex laboratory data. The laboratory can adjust the
      interpretation database to its specific needs, maintaining full control over
      program output. The structured input that 'MDI-LabLink' requires, supports
      dynamic test scheduling. It can be used to train personnel in the interpretation
      of laboratory test results. The program provides the clinician with a report that
      visualises the defect of the evaluated organ system with bitmap pictures and 3
      dimensional graphics. Patient follow-ups present in tabular and graphical form.
      Changes in the severity of the pathobiochemical defect, induced, for example, by
      therapy, are monitored automatically. Applications available include
      interpretations of isoenzyme patterns, diagnosis of urinary proteinuria and
      cerebrospinal fluid analysis.

PMID- 8740576
TI  - Learning clinical biochemistry using multimedia interactive clinical cases.

PMID- 8740577
TI  - 4-Pentafluoroethylumbelliferyl-beta-D-glucoside as a new fluorogenic substrate
      for acid beta-D-glucosidase.
AB  - 4-Pentafluoroethylumbelliferyl-beta-D-glucoside is proposed as an efficient
      substrate for human leukocyte acid beta-glucosidase. Its synthesis is described.
      This substrate was compared directly with 4-trifluoromethylumbelliferyl-beta-D
      glucoside synthesized by us earlier and with 4-methylumbelliferyl-beta-D
      glucoside which is commonly used for acid beta-glucosidase activity assay. The
      specific activity of acid beta-glucosidase with 4-pentafluoroethylumbelliferyl
      beta-D-glucoside was 3- and 8-fold higher than it was with the substrates
      mentioned above. The kinetic parameters KM and VMAX for human leukocyte acid beta
      glucosidase with the three substrates was determined. One possible application of
      the newly synthesized substrate is its use in the diagnosis of acid beta
      glucosidase hereditary deficiency (Gaucher's disease).

PMID- 8740578
TI  - Evaluation of nonisotopic binding assays for measuring vitamin B12 and folate in
      serum.
AB  - We report the evaluation of the microparticle enzyme immunoassay (MEIA) for
      estimating vitamin B12 and the ion capture (IC) assay for estimating folate in
      serum. The assays were performed with the Abbott IMx analyzer. Intra-assay
      coefficients of variation were from 3.4% to 8.0% for vitamin B12 and from 1.5% to
      4.2% for folate, respectively. Interassay coefficients of variation ranged from
      6.3% to 8.8% for vitamin B12 and from 3.9% to 11.3% for folate, respectively.
      Linearity was satisfactory, with an analytical recovery of 119 +/- 4% for vitamin
      B12 and 95 +/- 8% for folate. The detection limit was 56.2 pmol/l for vitamin B12
      and 1.9 nmol/l for folate. Results of these assays correlated well with those
      from the cloned enzyme donor immunoassay (CEDIA), our current routine method: r =
      0.97 for vitamin B12 (n = 47) and r = 0.97 for folate (n = 50). The MEIA and the
      IC assay were easy to perform with the IMx analyzer.

PMID- 8740579
TI  - Amniotic fluid for screening of lysosomal storage diseases presenting in utero
      (mainly as non-immune hydrops fetalis).
AB  - Seventy amniotic fluids (AF) were sampled because of abnormal ultrasound findings
      (mainly non-immune hydrops fetalis (54 cases) or of the presence of vacuolated
      lymphocytes in fetal blood (3 cases)). They were analysed by a procedure
      involving AF supernatant analysis (glycosaminoglycans, oligosaccharides, free
      sialic acid and acid hydrolase activities) and biochemical study of cultured AF
      cells. Ten cases of lysosomal storage diseases (LSD) were diagnosed. The reported
      procedure allows an orientating screening within 3 days by analysis of 15 ml of
      third trimester AF supernatant (except for Gaucher and Niemann-Pick diseases). In
      some cases, the results allow an LSD diagnosis and a medical abortion without
      waiting for the formal diagnosis (in cultured AF cells that needs 3 more weeks),
      considering the poor prognosis of these LSD presenting in utero. Furthermore, the
      formal assessment of the diagnosis in the cultured fetal cells allows accurate
      genetic counselling for the couple.

PMID- 8740580
TI  - Cholesteryl ester transfer activity in liver disease and cholestasis, and its
      relation with fatty acid composition of lipoprotein lipids.
AB  - Liver disease is accompanied by major qualitative and quantitative disturbances
      in plasma lipoprotein metabolism, the extent and intensity of which depend on the
      degree of parenchymal damage, cholestasis, or both. The main objective of this
      study was to determine the cholesteryl ester transfer CETP activity and its
      association with the lipoprotein neutral lipid composition in patients with
      either liver cirrhosis or cholestasis, as compared to normal controls.
      Lipoproteins were isolated by ultracentrifugation, lipids and apolipoproteins
      were measured by conventional methods, and the fatty acid composition was
      established by gas chromatography; CETP activity in lipoprotein-deficient plasma
      was measured by determining the transfer of [3H]cholesteryl esters from HDL to
      VLDL. Lipoprotein lipase and hepatic lipase activities were measured in post
      heparin plasma by radiochemical methods. In patients with liver cirrhosis, low
      levels of VLDL, HDL, apo B, and Lp(a) were observed, as well as a change in the
      composition of HDL particles, with increases in the relative proportion of
      triglyceride and free cholesterol. Respectively, the last two changes could be
      attributed in part to the low hepatic lipase activity observed in this study, and
      to the low lecithin:cholesterol acyltransferase activity previously observed by
      others. In patients with cholestasis, a moderate hyperlipidemia due to the
      elevation of LDL was found. In contrast, HDL and apo A-I levels were very low
      reflecting a low number of HDL particles, which also had altered compositions
      with increases in the triglyceride and free cholesterol contents relative to apo
      A-I and esterified cholesterol, respectively. As regards the fatty acid
      composition of lipoprotein lipids, the two groups of patients showed, in general,
      a lower proportion of linoleic acid and a compensating higher proportion of oleic
      acid as compared to the controls, changes that were observed in both cholesteryl
      esters and triglycerides. In contrast, the proportions of oleic and palmitoleic
      acids in phospholipids were increased, whereas that of stearic acid was decreased
      in patients as compared to controls. In patients with liver cirrhosis, as well as
      in controls, no changes were observed in the fatty acid compositions of
      cholesteryl ester, triglycerides, or phospholipids among the different
      lipoproteins, which probably reflects the equilibration reached by the action of
      CETP. In patients with cholestasis, no differences were observed in fatty acid
      composition among the lipoprotein phospholipids but, interestingly, cholesteryl
      esters from VLDL had a significantly lower linoleic acid content than those from
      HDL, whereas triglycerides from VLDL had significantly higher oleic acid and
      lower linoleic acid contents than those from HDL. This distinct fatty acid
      composition of the neutral lipids between lipoproteins was associated with a
      significant decrease (25%) in the cholesteryl ester transfer activity in patients
      with cholestasis. We suggest that fat malabsorption due to the biliary defect may
      induce a decrease in cholesteryl ester transfer protein synthesis or section,
      which in turn would slow the equilibration of the neutral lipids among plasma
      lipoproteins.

PMID- 8740581
TI  - Bile acid conjugation in early stage cholestatic liver disease before and during
      treatment with ursodeoxycholic acid.
AB  - The efficiency of bile acid conjugation before and during therapy with 600 mg/day
      of ursodeoxycholic acid was measured in seven adult patients with early chronic
      cholestatic liver disease (6 with primary biliary cirrhosis; 1 with primary
      sclerosing cholangitis). Duodenal bile samples were obtained by aspiration and
      the proportion of unconjugated bile acids was determined using lipophilic anion
      exchange chromatography to separate bile acid classes, followed by analysis of
      individual bile acids by gas chromatography-mass spectrometry. The proportion of
      conjugated bile acids was determined by high-performance liquid chromatography.
      Use of a (99m)Tc-HIDA recovery marker permitted the absolute mass of unconjugated
      bile acids in the gallbladder to be calculated. Unconjugated bile acids comprised
      0.4% of total biliary bile acids before and 0.2% during ursodeoxycholic acid
      therapy, indicating highly efficient conjugation of bile acids. During therapy,
      percentage unconjugated ursodeoxycholic acid significantly increased from (mean
      +/- S.D.) 13 +/- 13% to 54 +/- 12%; P < 0.002. When the unconjugated and
      conjugated fractions of bile acids were compared, there was an enrichment in
      unconjugated fraction for cholic acid and ursodeoxycholic acid and a depletion
      for chenodeoxycholic acid both in basal condition and during ursodeoxycholic acid
      therapy, suggesting that hydrophilic bile acids were conjugated less efficiently.
      During therapy, the conjugation efficiency significantly increased for cholic
      acid and ursodeoxycholic acid. The pretreatment mass of total unconjugated bile
      acids in the gallbladder was (mean +/- S.D.) 4.4 +/- 3.2 mumol, and was not
      significantly changed by ursodeoxycholic acid therapy (6.2 +/- 3.5 mumol).
      However, ursodeoxycholic acid therapy caused a significant increase in the mass
      of unconjugated ursodeoxycholic acid. It is concluded that endogenous bile acids
      and exogenous ursodeoxycholic acid when given at the usual dose are efficiently
      conjugated in patients with early cholestatic liver disease. Despite showing
      increased biliary unconjugated ursodeoxycholic acid during its oral
      administration, our data do not lend support to the occurrence of hypercholeresis
      due to cholehepatic shunting of bile acids.

PMID- 8740582
TI  - The carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) is a
      potential serum marker of ongoing liver fibrosis.
AB  - We report for the first time the measurement of the serum concentration of the
      carboxy-terminal cross-linked telopeptide of type I collagen in patients with
      various liver diseases. This breakdown product of type I collagen, which is the
      major collagen type found in fibrotic liver, was measured by a radioimmunoassay
      in the serum of 149 patients with various liver diseases and in 67 controls. Its
      concentration is significantly elevated (P < 0.05) above reference intervals in
      sera from patients with liver diseases, except in patients with chronic active
      hepatitis of unknown origin and in patients with acute hepatitis A. In the 143
      patients with liver fibrosis, the serum level of the carboxy-terminal telopeptide
      of type I collagen is correlated with the extent of fibrosis, as assessed by a
      histological scoring system (r = 0.3899, P < 0.0001), but not with inflammation
      and necrosis.

PMID- 8740583
TI  - Analysis of the deletion/insertion polymorphism of the angiotensin I-converting
      enzyme gene by capillary electrophoresis.

PMID- 8740584
TI  - Ketone body ratios of capillary blood compared with that of arterial blood.

PMID- 8740585
TI  - Effect of ascorbic acid deficiency on plasma prothrombin time and partial
      thromboplastin time in guinea pigs.

PMID- 8740586
TI  - Computer-assisted microscope characterization of BCNU-induced modifications in
      the collective behavior of 12 human brain cancer cell lines.
AB  - The aim of our study is to characterize the disturbance induced by repeated BCNU
      treatments in 12 human brain tumor cell lines in terms of their collective
      behavior. This collective behavior was characterized by means of the Delaunay
      triangulation and Voronoi mathematical paving techniques combined with the
      computer-assisted microscope analysis of Feulgen-stained nuclei. This methodology
      enabled growth to be characterized in terms of cell colony size and density. In
      addition to this colony pattern characterization, the DNA ploidy level was
      assessed by means of DNA histogram typing. The cell proliferation level was also
      determined. Ten astrocytic and two medulloblastoma cell lines treated weekly with
      BCNU were analyzed. Study of the cell colony architecture and cell proliferation
      revealed specific BCNU-induced modifications in connection with the origins of
      the cell lines, i.e. astrocytoma (AST), glioblastoma (GBM), or medulloblastoma
      (MED). The BCNU-induced effect on GBM (the more malignant of the cell lines) was
      very different in that proliferation was weakened, but the cell colony density
      increased after a latency phase. The decrease in cell colony density and cell
      proliferation of MED seems to indicate that they are more sensitive to BCNU than
      GBM, but relatively tolerant of this type of chemotherapy in comparison with AST.

PMID- 8740587
TI  - Secretion of matrix metalloproteinase-2 (72 kD gelatinase/type IV collagenase =
      gelatinase A) by malignant human glioma cell lines: implications for the growth
      and cellular invasion of the extracellular matrix.
AB  - Human glioma cells (T98G and A172 cell lines) were cultured on various
      extracellular matrix (ECM) components including type I, IV and V collagens,
      fibronectin, laminin, and reconstituted basement membrane (Matrigel), and the
      role of matrix metalloproteinases (MMPs) in their growth and invasion was
      examined. T98G glioma cells grew well on these ECM components and invaded the
      reconstituted basement membrane. In contrast, A172 glioma cells showed growth
      inhibition on collagen types IV and V and Matrigel without invasion of the
      Matrigel. Gelatin zymography and enzyme immunoassays demonstrated that T98G
      glioma cells, but not A172 cells, secrete a large amount of matrix
      metalloproteinase-2 (MMP-2, 72 kD gelatinase/type IV collagenase = gelatinase A),
      and this was confirmed by immunoblotting and immunohistochemistry. Of the two
      different tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), T98G cells
      produced only TIMP-1 during culture on Matrigel, whereas A172 cells secreted
      both. Although both human recombinant TIMP-1 and TIMP-2 stimulated T98G cell
      growth slightly on Matrigel, the in vitro invasiveness was significantly reduced
      by only recombinant TIMP-2. These results suggest that MMP-2 plays an important
      role in the ECM invasion of T98G human glioma cells in vitro.

PMID- 8740588
TI  - PROMACE-MOPP and intrathecal chemotherapy for CNS lymphomas.
AB  - We conducted a Phase II study of PROMACE-MOPP and intrathecal (IT) therapy
      followed by cranial radiation in 7 patients (4 male, 3 females) with diffuse
      large cell lymphomas (including one T cell) involving the central nervous system
      (CNS). Median age was 47 years (range, 25-78). Median performance status was 2
      (range, 2 to 3). Two patients had positive CSF cytology. No patients had prior
      chemotherapy or radiotherapy. Treatment consisted of PROMACE (cyclophosphamide
      650 mg/m2, etoposide 120 mg/m2 days 1 and 8, methotrexate (MTX) 1.5 g/m2 and
      folinic acid 50 mg/m2 (x 5) day 15, and prednisone 60 mg/m2 days 1-14) x 3-4
      courses. MOPP consisted of mustargen 6 mg/m2 and vincristine 1.4 mg/m2 days 1 and
      8, procarbazine 100 mg/m2 and prednisone 40 mg/m2 po days 1-14 x 3-4 courses. IT
      drugs were MTX 20 mg and hydrocortisone 20 mg day 1 and cytosine arabinoside 100
      mg day 8, courses 2 to 6, or more frequently if CSF cytology was positive.
      Following MOPP, 4000 cGy whole brain radiation (XRT) and 2000 cGy boost was
      given. Response was evaluated before XRT. Two patients declined XRT, 3 declined
      MOPP and 2 declined IT drugs. Two patients had extracerebral disease and 5 were
      primary CNS lymphomas. Response after PROMACE was CR: 3 patients; PR 2: stable 1.
      One patient, with extracerebral disease, experienced PR in the abdomen and CR by
      CT scan in the brain, but had persistent positive CSF cytology. This patient died
      from pneumocystis pneumonia 10 weeks after her last CSF cytology and 17 weeks
      after her diagnosis. After PROMACE +/- MOPP 6 patients experienced CR's. Median
      (range) survival was 100 (17-334) weeks, with 1 patient lost to follow up at 32
      weeks. Toxicity included febrile neutropenia; 6 patients; pneumocystis pneumonia:
      1 (fatal); thrombocytopenia; 5; stomatitis: 3; diarrhea; 2; nausea; 3.
      CONCLUSION: This regimen is active in the treatment of CNS lymphomas, although
      toxicity is substantial.

PMID- 8740589
TI  - A novel single-cell staining procedure performed in vivo under
      electrophysiological control: morpho-functional features of juxtacellularly
      labeled thalamic cells and other central neurons with biocytin or Neurobiotin.
AB  - We describe a novel and very effective single-cell labeling method with unique
      advantages for revealing the axonal and dendritic fields of any extracellularly
      recorded neuron. This procedure involves the use of fine glass micro-pipettes
      (tip diameter: approximately 1 micron), which contain biocytin or Neurobiotin
      dissolved in a salt solution, for the simultaneous juxtacellular recording and
      tracer iontophoresis. Once a neuron is well-isolated and identified, low
      intensity (< 10 nA) positive-current pulses are injected by way of the micro
      electrode such as to modulate its firing. Juxtacellular tracer iontophoresis may
      last as long as the cell electrophysiologically remains in good health, while
      determining some of its physiological properties. Control experiments, including
      the selective killing of previously injected cells, provide convincing evidence
      that it is the stained unit that was recorded and 'tickled' by the
      juxtamembranous iontophoretic pulses. Electrophysiological and histochemical data
      further show that neuronal filling could occur during an electrically induced,
      transient, physical micro-damage of a somatic or dendritic membrane patch. This
      simple, single-cell staining method has been used to label several types of rat
      brain neurons, including projection neurons and interneurons. Its success rate (
      > 86%) far exceeds that obtained by direct intracellular injections of tracers as
      shown by the labeling of a large sample of 100 individual cells (from 115
      attempts) in the thalamic reticular (Rt) nucleus of 33 rats. We thereby
      demonstrate that Rt cells project to restricted regions of a single thalamic
      nucleus, including anterior thalamic nuclei, and that the thalamus and Rt complex
      have reciprocal connections. The juxtacellular procedure thus represents an ideal
      directed single-cell labeling tool for determination of functional properties,
      for subsequent identification, for delineation of overall neuronal architecture
      and for tracing neuronal pathways, provided care is taken to avoid the possible
      drawbacks and pitfalls that are illustrated and discussed in the present paper.

PMID- 8740590
TI  - Experimental microneurosurgery of the trigeminal nerve: surgical technique for
      ganglionectomy and rhizotomy in the cat.
AB  - The techniques of two experimental surgical operations on the trigeminal nerve
      are described, namely, excision of the trigeminal ganglion (ganglionectomy) and
      division of the trigeminal root (rhizotomy), in the cat. These techniques have
      been developed with the specific aims of achieving the trigeminal lesion and also
      preserving a satisfactory postoperative quality of life for the animal in order
      to make it possible to study the long-term effects of trigeminal dennervation. To
      the best of our knowledge, a detailed description of such a surgical methodology
      is lacking; reporting of these procedures may facilitate future research on the
      trigeminal nerve.

PMID- 8740591
TI  - Concurrent reflectance imaging and microdialysis in the freely behaving cat.
AB  - We present a method to perform simultaneous microdialysis with light reflectance
      imaging of neural activity in a discrete brain region of the freely behaving
      animal. We applied this method to the dorsal hippocampus of freely behaving cats
      to (1) measure extracellular glutamate and reflectance variations across a sleep
      waking cycle, (2) assess spatially coherent neural activity changes accompanying
      local perfusion of cocaine and (3) measure local changes in cell volume induced
      by infusion of hyper- and hypo-osmotic solutions. Higher extracellular glutamate
      concentrations corresponded to higher imaged neural activity. Sequential images
      showed that cocaine perfusion elicited a propagating reflectance change as
      cocaine reached the tissue. Microperfusion of hypo-osmotic solution ( - 100
      mOsm), which increases cell volume, decreased reflectance. Microperfusion of
      hyperosmotic sucrose solutions, which reduce cell volume, increased reflectance
      in a dose-dependent manner. The data indicate that reflectance imaging can
      measure changes in cell volume, and could, thus, measure neural activity through
      activity/cell volume corollaries. Combining microdialysis and optical imaging
      enables investigation of the neurochemical bases of spontaneous neural activity
      patterns within discrete brain nuclei.

PMID- 8740592
TI  - Statistics for studying quanta at synapses: resampling and confidence limits on
      histograms.
AB  - This paper describes some statistical methods for working with data on quantal
      sizes. Since quantal sizes often do not fit to normal probability distribution
      functions, statistics based on the normal distribution are inappropriate.
      Resampling methods can be used to determine confidence limits and to test whether
      two sets of data differ by chance. Some hypotheses about the nature of quanta are
      based on apparent peaks and valleys in histograms. Confidence limits can be
      placed on the bins in the histogram by using the Kolomorogov-Smirnov statistic or
      by resampling. The confidence limits should assist in the evaluation of the
      significance of the valleys.

PMID- 8740593
TI  - Improved retrograde axonal transport and subsequent visualization of
      tetramethylrhodamine (TMR) -dextran amine by means of an acidic injection vehicle
      and antibodies against TMR.
AB  - We studied the ability of various dextran amines (DA) to retrogradely label
      cortical neurons to the full extent of their dendritic configurations.
      Corticothalamic neurons were labeled by pressure injection of DA into the
      ventrobasal thalamic nuclei of the rat brain. Of fluorescein-, Texas Red-,
      Cascade Blue- and tetramethylrhodamine (TMR)-DAs of MW 3000 and TMR-DA of MW
      10,000, neurons were most efficiently labeled with TMR-DA of MW 3000. The use of
      acidic vehicles (pH 1-3) for dissolving TMR-DA enhanced the retrograde labeling,
      as compared with that of a neutral vehicle. The retrograde labeling with TMR-DA
      was more clearly demonstrated by using anti-TMR antibodies; the indirect
      immunofluorescence method with a rhodamine-conjugated secondary antibody and
      immunoperoxidase method with a peroxidase anti-peroxidase (PAP) complex revealed
      that the dendrites of many corticothalamic neurons were filled with TMR-DA. The
      Golgi-like retrograde labeling of TMR-DA visualized by the PAP immunoperoxidase
      method was comparable with that of biotinylated DA by the avidin-biotinylated
      peroxidase complex method. Similar Golgi-like dendritic staining was observed
      among corticospinal neurons after injection of TMR-DA into the corticospinal
      tract of the spinal cord. Most apical dendrites of corticospinal neurons extended
      into layer I, whereas those of corticothalamic neurons ended in layer IV or the
      deep part of layer III. The TMR-DA injection under acidic conditions and
      immunostaining with the anti-TMR antibodies are considered to be a useful method
      to visualize the dendrite configuration of cortical projection neurons.

PMID- 8740594
TI  - Lumbar catheterization of the spinal subarachnoid space in the rat.
AB  - The method commonly used for catheterization of the lumbar subarachnoid space in
      the rat implies inserting the catheter through the atlanto-occipital (A-O)
      membrane and moving the catheter caudally along the spinal cord. The method is
      associated with a considerable morbidity. A method for direct catheterization of
      the lumbar subarachnoid space was therefore developed. Major surgery was avoided
      by using a catheter-through-needle technique. Of 32 rats, none died. There were
      no signs of neurological disturbances, and all animals gained weight as normal
      the first week after implantation. Data from rats catheterized by the A-O method
      were used for comparison. Of 40 animals, 2 died, 11 showed signs of neurological
      disturbances, and the mean weight was reduced during the first week after
      catheterization. The two groups of animals showed different behavioural responses
      to intrathecal injection of N-methyl-D-aspartate (NMDA, 0.1-1.6 mM, 15
      microliters) which is thought to stimulate afferent pathways mediating
      nociception. Animals with a lumbar catheter showed licking, biting and scratching
      behaviour in a dose-related manner for concentrations up to 1.6 mM. The animals
      with A-O catheters showed a maximum level of this behaviour already at 0.4 mM,
      while 0.5 mM induced convulsions. A possible explanation of this difference in
      response to NMDA could be a long-lasting pain state in the A-O group, caused by
      catheter-induced changes in the spinal cord and by the extensive surgery. It is
      concluded that the direct lumbar catheterization has several advantages compared
      to the A-O method, decreasing the suffering of the animals, the neurological
      disturbances and the interference with nociceptive functions of the spinal cord.

PMID- 8740595
TI  - An algorithm for high-resolution detection of postsynaptic quantal events in
      extracellular records.
AB  - A software package has been developed for the detection and measurement of
      extracellularly recorded postsynaptic quantal events evoked by neural
      stimulation. The algorithm is based on the identification of monotonic regions of
      a differentiated current signal and detects the small inflections and peaks of a
      postsynaptic response that result from the asynchronous presynaptic release of
      individual packets of neurotransmitter. Recorded and simulated postsynaptic
      responses have been used to verify the accuracy of the algorithm and to determine
      its resolution. The algorithm can accurately detect up to six individual quanta
      in a time period of 20 ms, with a resolution of 0.5-1.0 ms.

PMID- 8740596
TI  - Tissue swelling and intracellular pH in the CA1 region of anoxic rat hippocampus.
AB  - The fluorescent dye BCECF was used to simultaneously determine the intracellular
      pH (ratio 495 : 450 nm) and changes in relative tissue volume (fluorescence at
      the 450 nm isosbestic wavelength) in rat hippocampal slices. Anoxia in the
      presence of glucose caused tissue swelling and subsequent intracellular acidosis
      after a short and small transient alkaline peak. Reoxygenation reversed tissue
      swelling only partly and ended in persistent tissue swelling. The intracellular
      pH was initially further acidified before restoration to the normoxic
      intracellular pH occurred. Omitting glucose during anoxia caused similar but more
      marked changes of relative tissue volume. However, acidosis during anoxia was
      less marked and subsequently converted to alkalosis. Reoxygenation also caused
      initial acidification but the intracellular pH was not completely restored
      afterwards.

PMID- 8740597
TI  - An analytical review of 24 controlled clinical trials for fibromyalgia syndrome
      (FMS).
AB  - We performed a combined manual and computer search of the FMS literature to
      identify controlled clinical trials in FMS from 1980 to June 1994 inclusive. Our
      specific objectives were: 1) to determine which outcome measures have been used
      in clinical trials for FMS, and the methods utilized to measure these outcomes;
      2) to identify which outcome measures were most and least sensitive in
      distinguishing between treatment groups, and 3) to identify weakness in trial
      design. Our analysis of 24 clinical trials demonstrates the large diversity of
      outcome measures and measurement instruments that have been used to detect
      differences between treatment and placebo in the management of FMS. Whereas
      certain outcomes, such as self-reported pain and sleep quality, were frequently
      measured, other clinically important outcomes, such as functional and
      psychological status, were infrequently included in data collection. Finally, we
      identified several significant potential sources of bias, including potential
      flaws in subject selection and group allocation, inadequate randomization,
      incomplete blinding, errors in outcome measurement, and inappropriate analysis of
      data.

PMID- 8740598
TI  - Can stress-related shoulder and neck pain develop independently of muscle
      activity?
AB  - A case-control designed was used to investigate associations and interactions
      between muscle activity measured by surface electromyography (EMG) in the upper
      trapezius muscle and subjectively reported risk factors in workers with and
      without shoulder and neck pain. EMG data were collected both in the workplace
      (indicating vocational muscle activity) and in a laboratory setting (indicating
      non-specific muscle activity). Women in manual (15 pairs) and office (24 pairs)
      work were included. The pairs were matched on age, gender and on current and
      historical work load, such as working hours, type and length of employment.
      Previous reports of this study have indicated that shoulder and neck myalgia was
      associated with increased muscle activity for the manual workers, and with
      psychological and psychosocial factors for the office workers. These risk factors
      were in the present report used as the basis for studying associations and
      interactions between muscle activity (1), psychological and psychosocial factors
      (2), and shoulder and neck pain (3). Subjectively reported or perceived general
      tension, a stress symptom presumed related to psychosocial and psychological
      factors, was previously found to be the strongest and only variable separating
      cases and controls in both work groups. In this paper, no relationship was found
      between perceived general tension and EMG variables for the office workers. For
      the manual workers a strong interaction was found; perceived general tension
      correlated positively with EMG variables for the controls, and negatively with
      EMG variables for the cases. It is hypothesised that the feeling of general
      tension represents a physiological activation response that may or may not
      include muscle fibre activation. This implies that pain provoked by psychosocial
      stress factors may not be mediated through increased muscle activity.

PMID- 8740599
TI  - The influence of low back pain on muscle activity and coordination during gait: a
      clinical and experimental study.
AB  - Chronic low back pain (CLBP) is a major clinical problem with a substantial socio
      economical impact. Today, diagnosis and therapy are insufficient, and knowledge
      concerning interaction between musculoskeletal pain and motor performance is
      lacking. Most studies in this field have been performed under static conditions
      which may not represent CLBP patients' daily-life routines. A standardized way to
      study the sensory-motor interaction under controlled motor performances is to
      induce experimental muscle pain by i.m. injection of hypertonic saline. The aim
      of the present controlled study was to analyze and compare electromyographic
      (EMG) activity of and coordination between lumbar muscles (8 paraspinal
      recordings) during gait in 10 patients with CLBP and in 10 volunteers exposed to
      experimental back muscle pain induced by bolus injection of 5% hypertonic saline.
      When the results are compared to sex- and age-matched controls, the CLBP patients
      showed significantly increased EMG activity in the swing phase; a phase where the
      lumbar muscles are normally silent. These changes correlated significantly to the
      intensity of the back pain. Similar EMG patterns were found in the experimental
      study together with a reduced peak EMG activity in the period during double
      stance where the back muscles are normally active. Generally, these changes were
      localized ipsilaterally to the site of pain induction. The clinical and
      experimental findings indicate that musculoskeletal pain modulates motor
      performance during gait probably via reflex pathways. Initially, these EMG
      changes may be interpreted as a functional adaptation to muscle pain, but the
      consequences of chronic altered muscle performance are not known. New
      possibilities to monitor and investigate altered motor performance may help to
      develop more rational therapies for CLBP patients.

PMID- 8740600
TI  - Sensory-motor interactions of human experimental unilateral jaw muscle pain: a
      quantitative analysis.
AB  - Experimental muscle pain was elicited by bolus injection of 0.15 ml of 5%
      hypertonic saline into the human masseter muscle. The sensory experience was
      described using 10-cm visual analogue scales (VAS) and the McGill Pain
      Questionnaires (MPQ) on 10 subjects. Effects of pain on deliberately unilateral
      mastication were quantitatively assessed in 13 other male subjects using
      kinematic recordings of the mandible and jaw muscle electromyography (EMG). Jaw
      movement and EMG data were transformed into single masticatory cycles which were
      averaged within subjects to produce mean masticatory cycles. Injection of 5%
      saline through normal and anesthetized skin produced similar VAS profiles and MPQ
      features. Displacement of the mandible during painful mastication was
      significantly smaller in the vertical axis (10.0 +/- 11.5%, P < 0.05) and in the
      lateral axis (22.6 +/- 20.9%, P < 0.05) as compared to pre-pain values. The mean
      opening and closing velocities of the mandible were significantly reduced (10.5
      +/- 16.3% and 15.3 +/- 21.2%, P < 0.05) and the cumulated distance of the jaw
      movement was also significantly smaller during pain (10.5 +/- 11.8%, P < 0.05).
      Moreover, agonist EMG activity during pain was significantly lower in the
      ipsilateral masseter muscle (20.3 +/- 25.4%, P < 0.05) as compared to pre-pain
      root-mean-square (RMS) values. The observed sensory-motor interactions can be
      explained by a facilitatory effect of activity in nociceptive muscle afferents on
      inhibitory brain-stem interneurons during agonist action. Thus, generated
      movements have smaller amplitudes and they are slower which most likely
      represents a functional adaptation to experimental jaw muscle pain.

PMID- 8740601
TI  - Mechanisms of spontaneous tension-type headaches: an analysis of tenderness, pain
      thresholds and EMG.
AB  - Pericranial muscle tenderness, EMG levels and thermal and mechanical pain
      thresholds were studied in 28 patients with tension-type headache and in 30
      healthy controls. Each patient was studied during as well as outside a
      spontaneous episode of tension-type headache. Outside of headache, muscle
      tenderness and EMG levels were significantly increased compared to values in
      controls subjects, while mechanical and thermal pain thresholds were largely
      normal. During headache, muscle tenderness evaluated by blinded manual palpation
      increased significantly, while pressure pain thresholds remained normal and
      pressure pain tolerances decreased. Thermal pain detection and tolerance
      threshold decreased significantly in the temporal region, but remained normal in
      the hand. EMG levels were unchanged during headache. It is concluded that one of
      the primary sources of pain in tension-type headache may be a local and
      reversible sensitization of nociceptors in the pericranial muscles. In addition,
      a segmental central sensitization may contribute to the pain in frequent
      sufferers of tension-type headache.

PMID- 8740602
TI  - Cognitive coping and appraisal processes in the treatment of chronic headaches.
AB  - The purpose of the present study was to investigate the active cognitive
      ingredients of change in psychological treatments for long-term chronic headache
      complaints. The primary questions this study addressed were: (1) Is a cognitive
      self-hypnosis training which explicitly attempts to change appraisal and
      cognitive coping processes more effective in producing these changes than a
      relaxation procedure, and (2) are changes in pain appraisal and cognitive coping
      related to changes in pain and adjustment in the short and long term? A total of
      144 patients were assigned at random to a cognitive self-hypnosis (CSH) treatment
      or autogenic training (AT) with a duration of 7 weeks. Measures used were:
      Headache Index (HI), Symptom Checklist-90 (SCL-90), Coping Strategy Questionnaire
      (CSQ), Multidimensional Locus of Pain Control Questionnaire (MLPC) and treatment
      expectations. The results indicated that patients successfully changed their use
      of coping strategies and pain appraisals. Cognitive therapy was more effective
      than relaxation training in changing the use of cognitive coping strategies which
      were the direct targets of treatment. However, treatment effects were only
      related with changes in the use of coping strategies and appraisal processes to a
      limited extent and the mediational role of cognitive processes in pain reduction
      and better adjustment was inconclusive.

PMID- 8740603
TI  - Transcutaneous electric nerve stimulation (TENS) during distension shoulder
      arthrography: a controlled trial.
AB  - Transcutaneous electric nerve stimulation (TENS) is a safe and simple form of
      analgesia but is little used as an adjunct to local anaesthesia during routine
      procedures. This trial investigates the use of TENS in the radiology department
      using distension shoulder arthrography for 'frozen shoulder', a moderately
      painful procedure, as a model. Sixty patients with a clinical diagnosis of
      'frozen shoulder' were randomised to receive high-intensity TENS, low-intensity
      TENS or to act as controls. A standard procedure was then performed. Following
      the procedure patients completed a visual analogue pain scale. Mean recorded pain
      levels were lower in the TENS groups with a 50% difference between the high
      intensity group and a 38% difference between the low-intensity group as compared
      to control (difference statistically significant P < 0.01 and P < 0.05,
      respectively). TENS was well tolerated by patients. The 50% reduction in mean
      pain levels supports the use of TENS for routine painful procedures.

PMID- 8740604
TI  - A new method of recording somatosensory evoked potentials by randomized
      electrical tooth stimulation with 6 levels of intensity.
AB  - Dental somatosensory evoked potentials (SEPs) corresponding to the stimulus
      intensity levels were recorded at 6 different levels of intensity presented in a
      randomized order. The relationships between the amplitude of the late SEP
      component with latency between 150 and 300 msec and each stimulus intensity level
      were also compared in conditions of randomized intensity and constant intensity.
      The amplitude of the late component increased significantly with the increased
      stimulus intensity both in the randomized and constant intensity stimulation. The
      amplitude of the late component in the randomized stimulation with a 1-sec
      interstimulus interval (ISI) increased in the same manner as that in the constant
      intensity condition with a 1-sec ISI. The randomized stimulation with the
      prolonged ISI increased the amplitude of the late component. The latency of the
      late positive component significantly increased with the randomized stimulation
      with a 3-sec ISI. This phenomenon might be attributable to the psychological
      contamination. SEP recording in the randomized dental stimulation with a 1-sec
      ISI may have applications in neuropharmacological research or physiological
      research on pain and evaluation of the effects of analgesics, anesthetics,
      acupuncture and transcutaneous electrical nerve stimulation (TENS).

PMID- 8740605
TI  - The effects of isoflurane on repeated nociceptive stimuli (central temporal
      summation).
AB  - Central temporal summation of afferent nociceptive stimuli is involved in central
      hyperexcitability. This is assumed to be an important mechanism in the
      nociceptive system which is probably activated during surgery and trauma. The
      purpose of the present study was to investigate if isoflurane has a specific
      effect on central temporal summation in humans. Facilitation of the nociceptive
      reflex to repeated stimuli can be used to assess central summation in subjects
      unable to cooperate due to an anaesthetic procedure. The nociceptive reflex to
      single and repeated (5 pulses delivered at 2 Hz) electrical surface stimuli of
      the sural nerve were measured in 6 healthy volunteers anaesthetized with
      isoflurane. A reflex was defined as an EMG signal from the rectus and biceps
      femoris exceeding 20 microV for more than 10 msec in the 80-200 msec interval
      after the stimulus. The end-tidal isoflurane concentration was increased in steps
      of 0.25 vol% from 0.25 to 1.50 vol%. For each concentration the thresholds for
      the nociceptive reflex were determined as the current intensity that could just
      elicit a reflex response to single stimulations, and for the repeated
      stimulations as the current intensity that could just elicit a reflex response to
      the 4th and/or 5th stimuli in the train of 5 stimuli. The nociceptive reflex to
      single stimuli was depressed at isoflurane concentrations producing sedation or
      light anaesthesia (0.25-0.50 vol% end-tidal). In contrast, 2-4-fold higher
      isoflurane concentrations (1.00-1.50 vol% end-tidal) that normally produce
      surgical anaesthesia were required to depress the nociceptive reflex to
      repetitive stimuli. This indicates that central temporal summation in the
      nociceptive system is a potent mechanism, and that isoflurane has a weak potency
      for depressing temporal summation in humans. As such isoflurane alone is not
      adequate for inhibiting surgically evoked hyperexcitability.

PMID- 8740606
TI  - NMDA receptor blockade in chronic neuropathic pain: a comparison of ketamine and
      magnesium chloride.
AB  - Ten patients (4 female, 6 male) aged 34-67 years suffering from peripheral
      neuropathic pain participated in a double-blind placebo-controlled study where
      ketamine or magnesium chloride were administered by a 10 min bolus infusion
      (ketamine: 0.84 mumol/kg = 0.2 mg/kg, magnesium: 0.16 mmol/kg) followed by a
      continuous infusion (ketamine: 1.3 mumol/kg/h = 0.3 mg/kg/h, magnesium: 0.16
      mmol/kg/h). Ongoing pain determined by VAS score, area of touch-evoked allodynia,
      detection and pain thresholds to mechanical and thermal stimuli were measured
      before and during drug infusion. Ketamine produced a significant reduction of
      spontaneous pain (57%) and of the area of allodynia (33%). Magnesium chloride
      reduced pain (29%) and area of allodynia (18%) insignificantly. Following
      ketamine there was a significant correlation between the reduction in ongoing
      pain and reduction in area of touch-evoked allodynia. Detection and pain
      thresholds to mechanical and thermal stimuli were not significantly changed by
      the drugs. These findings suggest that both ongoing pain and touch-evoked pain
      (allodynia) in neuropathic pain are inter-related phenomena, which may be
      mediated by the same mechanism and involving a N-methyl-D-aspartate receptor.

PMID- 8740607
TI  - Amitriptyline effectively relieves neuropathic pain following treatment of breast
      cancer.
AB  - The effectiveness of amitriptyline in relieving neuropathic pain following
      treatment of breast cancer was studied in 15 patients in a randomised, double
      blind placebo-controlled crossover study. The dose was escalated from 25 mg to
      100 mg per day in 4 weeks. The placebo and amitriptyline phases were separated by
      a 2-week wash-out period. Visual analogue and verbal rating scales were used for
      the assessment of pain intensity and pain relief. Other measures included the
      number of daily activities disturbed by the pain, the Finnish McGill Pain
      Questionnaire, adverse effects, anxiety, depression, pressure threshold and grip
      strength. Amitriptyline significantly relieved neuropathic pain both in the arm
      and around the breast scar. Eight out of 15 patients had a more than 50% decrease
      in the pain intensity ('good responders') with a median dose of 50 mg of
      amitriptyline. The 7 patients who had a less than 50% effect had drug
      concentrations equaling those of the good responders. The 'poor responders'
      reported significantly more adverse effects with amitriptyline and placebo than
      the good responders. It is concluded that amitriptyline effectively reduced
      neuropathic pain following treatment of breast cancer. However, the adverse
      effects of amitriptyline put most of the patients off from using the drug
      regularly.

PMID- 8740608
TI  - Traumatic nociceptive pain activates the hypothalamus and the periaqueductal
      gray: a positron emission tomography study.
AB  - The study was conducted to investigate which areas of the brain respond to a
      painful encounter of minor dermal injury (a model of clinical pain) elicited by
      intracutaneous injection of a minute amount of ethanol. Four healthy volunteers
      (27-46 years) were subjected to positron emission tomographic (PET) investigation
      of regional cerebral blood flow (rCBF), using [15O]butanol as tracer. The ethanol
      (20 microliters, 70%) and saline (20 microliters, 0.9%) were injected
      intracutaneously 3 times in a single-blinded, semi-randomised manner for the pain
      experiment. All the injections were performed, adjacent to each other, at the
      lateral aspect of the right upper arm. Subjective sensory intensity of pain,
      unpleasantness and anxiety were rated with separate 100-mm visual analogue scales
      together with the Spielberger's State Anxiety Inventory (Spielberger et al. 1970)
      and heart rate. Paired-subtraction (pixel-by-pixel) between ethanol and saline
      was performed. Traumatic pain significantly caused higher ratings of intensity
      and affect scales, i.e., pain intensity, unpleasantness and increased sympathetic
      activity (evidenced by tachycardia). In contrast the anxiety rating remained
      unchanged. Acute traumatic nociceptive pain prominently activated the
      hypothalamus and periaqueductal gray (PAG). In addition, activations of the
      prefrontal cortex (PFC), insular, anterior cingulate cortex (ACC), posterior
      parietal cortex (PPC), primary motor/somatosensory areas (MI/SI: face, upper
      arm), supplementary motor area (SMA), and cerebellum were also demonstrated. The
      central processing of the pain-relevant/anticipatory arousal also engaged the
      PAG. This study demonstrates the involvement of the human cerebral cortex in
      perception, arousal, cognitive evaluative processes, and, hence, affective
      reactions (somatic/ autonomic outflow) associated with pain. The pain stimulus of
      traumatic character may, by its very nature, evoke the central processing to
      involve both the hypothalamus and the PAG.

PMID- 8740609
TI  - Role of endothelin in mediating neurogenic plasma extravasation in rat dura
      mater.
AB  - In addition to their potent vasoconstrictor properties, the endothelins
      (endothelin-1 and -3) may possess neurotransmitter/neuromediator and
      neuroendocrine actions. The aim of the present study was to evaluate the role of
      endothelins (ET) in mediating neurogenic inflammation of cephalic tissues in the
      rat. For this purpose, bosentan, a specific non-peptide mixed antagonist of ET
      receptors, was tested in rat models of neurogenic and non-neurogenic plasma
      extravasation in the dura mater and extracranial tissues (eyelid, conjunctiva,
      lip, tongue). Bosentan was effective for preventing neurogenic inflammation in
      the dura mater induced by unilateral electrical stimulation of the trigeminal
      ganglion or intravenous injection of capsaicin, whereas it was ineffective in
      extracranial tissues or after injection of substance P (non-neurogenic
      inflammation). The effect of nerve fiber stimulation on ET plasma concentrations
      in superior sagittal sinus was measured using selective radioimmunoassays for ET
      1 and -3. Endothelin-3 concentration significantly increased after intravenous
      injection of capsaicin, whereas ET-1 levels remained unchanged. Competition
      binding assays on microsomal membranes from the trigeminal ganglion revealed a
      single class of binding sites with equal affinity for ET-1 and ET-3, suggesting a
      homogenous population of ETB receptors. The role of ETB receptors in mediating
      inflammation was evidenced by the lack of efficacy of a selective ETA receptor
      antagonist, in contrast to the full efficacy of a selective ETB receptor
      antagonist, for preventing neurogenic inflammation induced by unilateral
      stimulation of the trigeminal ganglion. The role of ETB receptors was finally
      confirmed by the observation that exogenous administration of the ETB receptor
      agonist sarafotoxin S6c also induced plasma protein extravasation in the dura
      mater. This extravasation was not a direct effect of ETB receptor stimulation,
      because it was inhibited by spantide, a selective tachykinin receptor antagonist.
      These data strongly suggest that ET, acting through ETB receptors, may play an
      important role in mediating neurogenic inflammation in the meninges of rats.
      Since the profile of activity of bosentan is similar to that of the 5-HT1D/B
      agonists, sumatriptan and ergot alkaloids, one may speculate that ET receptor
      antagonists might be potentially effective in the treatment of acute migraine
      attacks.

PMID- 8740611
TI  - Variation in the placebo effect in randomised controlled trials of analgesics:
      all is as blind as it seems.
AB  - The objective was to investigate the relationship between pain relief scores
      produced by placebo and by active interventions in randomised controlled trials
      (RCTs). Individual patient categorical pain relief scores from 5 placebo
      controlled single-dose parallel-group RCTs in acute postoperative pain were used
      to calculate the percentage of the maximum possible pain relief score
      (%maxTOTPAR) for the different treatments. One hundred and thirty of the 525
      patients in the 5 trials had a placebo. Individual patients' scores with placebo
      varied from 0 to 100% of the maximum possible pain relief. The proportion who
      obtained more than 50% of the maximum possible pain relief with placebo varied
      from 7% to 37% across the trials; with the active drugs the variation was from 5
      to 63%. Mean placebo scores were related to the mean score for the active
      treatments in each study; the higher the mean active score, the higher the mean
      placebo score. This relationship disappeared when median values were used.
      Medical folklore has it that the amount of relief obtained with placebo is one
      third of the maximum possible (and does not vary), and that one-third of patients
      respond to placebo. The results show that the amount of relief obtained with
      placebo varies considerably between patients, that 38% of patients obtained more
      than 10% of the maximum possible relief, and 16% obtained greater than 50%. In
      double-blind, randomised parallel-group studies of high quality placebo scores
      should not vary. Despite these conditions being met the placebo scores did vary.
      The previous explanation, of a relationship between the mean placebo scores and
      the mean scores for the active treatments was not supported.

PMID- 8740610
TI  - Intraplantar injection of nerve growth factor into the rat hind paw: local edema
      and effects on thermal nociceptive threshold.
AB  - Nerve growth factor (NGF) is known to produce hyperalgesia as well as to
      stimulate synthesis of neuropeptides in dorsal root ganglia (DRG). In the present
      study, we wanted to determine the effects of local NGF administration and assess
      to which extent mast cell-dependent factors are mediating NGF responses. Rats
      received 1 daily unilateral intraplantar injection for 3 days. Local edema (days
      1-3), changes in thermal nociceptive threshold (days 1-4), and the content of
      calcitonin gene-related peptide (CGRP) and substance P (SP) in the sciatic nerve
      (day 4), were determined. NGF injection caused edema which was absent in rats
      pretreated with compound 48/80 as well as in rats treated neonatally with
      capsaicin ('capsaicin denervation'). NGF-induced edema was not reduced by the
      neurokinin-1 receptor antagonist SR140333, but attenuated by the CGRP receptor
      antagonist CGRP[8-37]. On each day, NGF injection caused a decrease in thermal
      nociceptive threshold which lasted for less than 3 h. Capsaicin denervation, but
      not treatment with indomethacin, abolished NGF-induced thermal hyperalgesia.
      Treatment with compound 48/80 attenuated hyperalgesia produced by the first, but
      not by subsequent, NGF injections. On day 4, 24 h after the last of 3 NGF
      injections, thermal nociceptive threshold was not different from control values,
      but at that time, CGRP and SP were elevated in the sciatic nerve. We suggest
      therefore that NGF-induced local edema was caused by mast cell-derived vasoactive
      compounds which act together with afferent neuron-derived CGRP to increase
      vascular permeability. NGF-induced thermal hyperalgesia most likely was caused by
      an increased sensitivity of peripheral endings of capsaicin sensitive afferents.
      This effect of NGF was not mediated by products of the cyclooxygenase pathway,
      and was also observed in mast cell-depleted rats.

PMID- 8740612
TI  - A double-blind randomised comparison of the effects of epidural clonidine,
      lignocaine and the combination of clonidine and lignocaine in patients with
      chronic pain.
AB  - Twenty patients with chronic pain who previously had obtained analgesia from
      epidural clonidine and lignocaine agreed to participate in a double-blind
      crossover study of lumbar epidural clonidine (150 micrograms), lignocaine (40 mg)
      and the combination of clonidine (150 microgram) and lignocaine (40 mg), all
      drugs were given in a volume of 3 ml. There were 11 women and 9 men with a mean
      age 53 years (range: 23-78 years); 9 patients had low back and leg pain, 9 had
      neuropathic pain, 1 had pelvic pain and 1 Wegner's granulomatosis. Pain intensity
      and pain relief, as well as sensory and motor blockade, were assessed for 3 h
      following each injection. The combination was reported as the best pain relief by
      12 of the 17 patients who completed all three arms of the study; 4 patients
      reported that clonidine was the best, 1 patient reported that none of the
      injections provided any analgesia and no patient reported that lignocaine was the
      best. SPID analysis revealed a significant difference between the combination and
      lignocaine (P < 0.05) but no other significant difference. TOTPAR analysis
      revealed no significant difference between any of the injections. All 3
      injections produced evidence of neurological blockade; clonidine produced sensory
      blockade in 3 patients and motor blockade in 3 patients. Lignocaine produced
      sensory blockade in 6 patients and motor in 8 patients, while the combination
      produced evidence of neurological blockade in all 17 patients, sensory in 6 and
      motor in 11 patients. Overall there was no relationship between neurological
      blockade and analgesia. The reported side effects appeared to be related to
      clonidine. These data indicate that in these patients with chronic pain epidural
      clonidine had a supra-additive effect and behaved more like a co-analgesic than a
      pure analgesic.

PMID- 8740613
TI  - Formalin-evoked activity in identified primary afferent fibers: systemic
      lidocaine suppresses phase-2 activity.
AB  - Formalin injected subcutaneously into the paw is a frequently used pain assay; it
      evokes an initial period of licking and flinching followed by a period of
      quiescence and last by a second period of intense and protracted licking and
      flinching. The prominent second phase is believed to reflect the development of a
      central (spinal cord) facilitation. This conclusion is based on the assumption
      that formalin evokes an initial burst of activity in fine afferent fibers,
      followed by prolonged low levels of activity in C fibers. Detailed reports
      substantiating this essential assumption have not been published. Thus, we
      recorded in situ from single sural nerve fibers, identified by their conduction
      velocity and modality, in the barbiturate anesthetized rat. Following formalin
      (2.5%, 50 microliters) injection into their receptive fields, phase-1 activity
      was prominent in A beta and A delta fibers as well as in high-threshold C
      nociceptive afferent fibers. Phase-2 activity was observed in A delta fibers with
      receptive fields in hairy skin and in all mechanically sensitive C fibers. Mean
      phase-2 activity in these fibers was 1/2-2/3 of the magnitude achieved in phase
      1. Mechanically insensitive fibers and A delta and C fibers with receptive field
      centers outside of the injection zone began firing 15 min or more post-injection
      and would contribute to phase-2, but not phase-1, behavioral activity.
      Intravenous infusion of low doses of lidocaine yielding plasma levels of 3.6-7.9
      micrograms/ml administered during phase 2 blocked formalin-evoked activity in
      primary afferent fibers in a dose-related fashion without blocking either
      electrically or mechanically evoked activity. Effective plasma doses were
      comparable to those found to relieve neuropathic pain. These data indicate that
      phase 2 in the formalin test is more closely related to ongoing afferent input
      than had previously been thought.

PMID- 8740614
TI  - Age is the best predictor of postoperative morphine requirements.
AB  - The dose of opioid prescribed for postoperative pain relief has traditionally
      been based on the weight of the patient. Although a reduction in dose is often
      suggested for elderly patients over 70 years of age, age-related alterations to
      dose are generally not considered for younger patients. The records of 1010
      patients, under 70 years old, prescribed morphine via patient-controlled
      analgesia (PCA) after major operations were examined to see what factors might
      best predict the amount of morphine used in the first 24 h after surgery. Factors
      included were age, sex, weight, operative site, verbal numeric pain score (at
      rest and on movement) and a nausea/vomiting score. In a subgroup of 78 of these
      patients, the effects of intraoperative and recovery room doses of opioid
      ('clinical' loading dose) were analysed. Although the interpatient variability in
      PCA morphine doses was large (differences of up to 10-fold in each age group),
      the best predictor of PCA morphine requirement in the first 24 h after surgery
      (the amount required in the 24 h after the initial loading dose) was the age of
      the patient. An estimate of these requirements for patients over the age of 20
      years can be obtained from the formula: average first 24 h morphine requirement
      (mg) = 100 - age. PCA allows patients the flexibility to titrate their own opioid
      dose; if conventional analgesic regimens are to become more effective, they too
      need to allow for the wide interpatient variation in dose requirements. Although
      previous studies have noted a correlation between patient age and the amount of
      opioid needed, this study quantifies this correlation and provides guidelines for
      opioid dosing. Prescriptions for conventional analgesic regimens should include a
      dose range centred on values obtained from the above formula to allow for the
      large interpatient variation in each age group. While initial morphine dose
      should be guided by patient age and not weight, subsequent doses must still be
      titrated according to effect.

PMID- 8740615
TI  - Expression of mu- and kappa-, but not delta-, opioid receptor mRNAs is enhanced
      in the spinal dorsal horn of the arthritic rats.
AB  - The expression of the mRNAs for mu-, delta- and kappa-opioid receptors was
      studied in the lumbar spinal cord of the rats with the inflammation at their
      unilateral hindpaw using in situ hybridization technique. On 11 days after the
      first adjuvant inoculation, mu- and kappa-opioid receptor mRNA levels in laminae
      I-II of the spinal dorsal horn ipsilateral to the inflamed hindpaw were increased
      to 135.3 +/- 6.4% and 130.3 +/- 5.7%, respectively, compared with the
      contralateral side. At this time point, no significant differences in the mu- and
      kappa-opioid receptor mRNA expression were observed between ipsi- and
      contralateral sides of other laminae. On the other hand, no significant change
      was observed in the delta-opioid receptor mRNA expression throughout the laminae
      I-IX at any time points examined. These findings suggest the increase in the
      synthesis of mu- and kappa-, but not delta-, opioid receptors in the spinal
      laminae I-II during sustained inflammatory pain.

PMID- 8740616
TI  - Concerning the homology of painful experiences and pain descriptors: a
      multidimensional scaling analysis.
AB  - How is the sensory (or other) experience of pain related to the words used to
      describe such experiences? Answering this question would not only improve our
      general understanding of the relationship between the experience of pain and the
      report of pain, but also would allow one to quantify inaccuracies or
      idiosyncracies in this regard. A continuous multidimensional scaling model was
      used to examine the similarity between noxious electrocutaneous stimuli and the
      words used to describe them. If these two types of stimulus objects were
      homologous, one would expect that physical and verbal stimuli with the same
      meaning would be scaled with similar values along a single dimension; if not, the
      two types of stimuli would be scaled at opposite poles of a dimension which
      distinguished between them. Twenty-five subjects rated the similarity of all
      pairs of 16 stimulus objects: 8 electrocutaneous stimuli (3-235 mW) and 8 verbal
      descriptors of such stimulation (from Slight Sensation to Severe Pain). A single
      dimension in the group stimulus space scaled both physical and verbal stimulus
      objects from least to greatest intensity. Since this (or any higher) dimension
      failed to segregate verbal from physical stimuli, the words appear to be
      homologous with experience. While conclusions are limited to these specific
      stimuli, results suggest that the INDSCAL model offers a valuable method for
      exploring the relationship between pain report and pain experience.

PMID- 8740617
TI  - The influence of warning signal timing and cognitive preparation on the
      aversiveness of cold-pressor pain.
AB  - This study examined the role of prior warning time, cognitive preparation and
      self-efficacy in the reaction to cold-pressor pain that has a substantial
      stimulus duration and leaves a residual effect. Forty-eight, paid, male subjects
      were randomly assigned to one of 3 cognitive preparation groups: (1) Training
      group, provided with a self-instructional booklet of pain control techniques, (2)
      Citizenship group, to control for reading a booklet, and (3) Control group with
      no advanced preparation. Warning times used on a within-subjects basis were 0,
      30, and 180 sec prior to immersion of their arms in cold water. Results indicated
      that overall, the 180 sec warning time yielded the lowest pain ratings. Warning
      time had no effect on duration in water for subjects who underwent training, but
      the 30 sec and 180 sec warning time yielded longer duration in water, for
      subjects in the other groups. The Training group preparation was effective in
      raising perceived self-efficacy for coping with pain which, in turn, was found to
      be correlated with pain tolerance. Perceived self-efficacy was also found to have
      an effect on heart rate with high scorers yielding a lower reaction upon
      immersion into the cold water compared to the low scorers. The results point to
      the need to consider the effect of the stimulus characteristics and the
      centrality of perceived self-efficacy when preparing a subject prior to pain
      stimulation.

PMID- 8740618
TI  - Memory for labor pain: context and quality.
AB  - The accuracy of memory for labor pain context and quality was examined in 33
      women who had given birth 3-4 years previously, utilizing the McGill Pain
      Questionnaire and unstructured recollections of childbirth events. Subjects
      displayed very good memory for the context of labor pain but poor memory for its
      quality. In order to test whether recall was influenced by semantic information a
      second study investigated the extent and type of knowledge which exists about the
      nature of labor pain amongst 33 women who had never given birth. The description
      of labor pain provided by nuliparous women was found to be similar in terms of
      category selection and descriptors to that of parous women. This suggests that
      women have available semantic information about labor pain which may influence
      their pain recall or even their assessment of a pain experience.

PMID- 8740619
TI  - Comments on Gunn (PAIN, 60 (1995) 349-350)

PMID- 8740620
TI  - Two in one: the genesis of central pain.

PMID- 8740621
TI  - Comments on Thurston and Randich.

PMID- 8740622
TI  - Analgesia and oral opioid consumption: strengths and shortcomings of methods.

PMID- 8740623
TI  - Comments on Stubhaug, Grimstad and Breivik, PAIN, 62 (1995) 111-118.

PMID- 8740624
TI  - Comments on Pentland and Donald.

PMID- 8740625
TI  - Clustering of pathological features in Alzheimer's disease: clinical and
      neuroanatomical aspects.
AB  - We have analyzed the tendency of amyloid load, neuritic plaques and
      neurofibrillary tangles (NFT) in the hippocampus and neocortex to occur in
      clusters in 49 consecutive cases of Alzheimer's disease (AD). This clustering
      tendency of the pathology was analysed in relation to severity of clinical
      disease assessed within 6 months before death, duration and age at onset of
      disease and at death. Amyloid plaques showed only a slight tendency to cluster
      together while neuritic plaques and, even more, NFT were clearly clustered. A
      greater clustering tendency was associated with more severe clinical impairment
      with particularly strong correlations being found between the clustering tendency
      of NFT in the hippocampus and clinical memory deficit, and between the clustering
      tendency of NFT in the parietal neocortex and overall cognitive deficit. Neuritic
      plaques showed similar but less pronounced and robust correlations between
      clustering and cognitive status. In the hippocampus NFT clustering was also
      negatively correlated with age at death, but not duration of disease nor age of
      disease onset. We conclude that clustering characterises neuritic pathology but
      not diffuse amyloid deposits and significantly affects cognition. The
      discrepancies between the group diagnosed as AD-only and the patient group that
      contained all patients, including the ones with mixed pathology, lead us to
      believe that any additional pathology might have a significant effect on the
      cognitive status of AD patients.

PMID- 8740626
TI  - Cortical synaptic changes and gliosis in normal aging, Alzheimer's disease and
      frontal lobe degeneration.
AB  - The most important new development during recent years in the field of
      degenerative dementia concerns synaptic pathology. So far it has been
      investigated in some regions and some cortical laminae in Alzheimer's disease
      (AD). The present communication is a more comprehensive study of all laminae in
      four different regions, the prefrontal, parietal, inferior temporal and posterior
      cingulate cortex. Against the background of normal aging, AD was compared with
      another degenerative disorder, frontal lobe degeneration of non-Alzheimer type
      (FLD). The synapse density was measured using synaptophysin as a marker.
      Astrocytes were also counted in the molecular layer. In normals, the cortex
      showed successively lower synaptic density from layer I to layer VI and
      relatively lowest density in the prefrontal cortex and a general decline with
      increasing age. A 46-49% decrease in synaptic density was found in all laminae in
      all regions of AD brains, a finding different from that in FLD. The number of
      astrocytes increased significantly in the prefrontal cortex both in AD and FLD
      but parietally only in AD. These results contribute to the understanding of
      normal synaptic organization of cortex, demonstrate the laminar and regional
      distribution of synaptic loss in AD and underscore the difference between AD and
      FLD. The gliosis appears to be secondary to the neurodegenerative changes.
      Synaptic loss is likely to be a common pathogenetic feature of neurodegenerative
      disorders and a likely cause of clinical symptoms and regional metabolic
      decrements in dementia.

PMID- 8740627
TI  - Differential susceptibility to neurofibrillary pathology among patients with Down
      syndrome.
AB  - Individual differences in the development of neurofibrillary changes were
      examined in eight cortical regions in the brains of 43 subjects with Down
      syndrome (DS; age range, 15-69 years) using sections stained with monoclonal
      antibodies (mAb) tau-1 and 3-39. Neurofibrillary pathology was found in 4 cases
      below 36 years of age and in all 20 cases above that age. In the 24 positive
      cases, numerical density of pretangles stained with tau-1 and 3-39, respectively,
      was 6.1/mm2 and 0/mm2; early tangles, 5.0/mm2 and 5.3/mm2; mature tangles,
      4.0/mm2 and 5.0/mm2 (p < 0.01); and end-stage tangles, 0.04/mm2 and 2.5/mm2 (p <
      0.001). Numerical density of pretangles stained with mAb tau-1 and tangles and
      plaques stained with mAb 3-39 correlates weakly with age (r = 0.43; p< 0.02), and
      together with the wide range of numerical densities suggested heterogeneity of
      the population examined. Cluster analysis based on two variables - i.e.,
      numerical density of pretangles stained with mAb tau-1 and neurofibrillary
      tangles (NFTs) and plaques stained with mAB 3-39, distinguished three groups of
      subjects with severe, moderate and weak changes. The severely affected group of 5
      subject (21%) had an average 54.6/mm2 of neurons and 13.9/mm/ plaques with
      neurofibrillary changes, whereas the moderately affected group (6 subjects; 25%)
      showed a significantly lower numerical density of neurons and plaques with
      neurofibrillary changes (25.7/mm2 and 8.1/mm2, respectively) as compared with the
      most affected group. Most of the subjects (13; 54%) belong to the third group
      with only 2.2/mm2 of neurons and 1.4/mm2 plaques with neurofibrillary pathology.
      Comparison of these three groups of Down syndrome subjects representing high,
      moderate, and low susceptibility to neurofibrillary changes with the general
      population suggests that the risk of Alzheimer disease is similar but the onset
      of pathological changes is earlier in DS.

PMID- 8740628
TI  - An atypical neuroleptic drug in the treatment of behavioural disturbances and
      psychotic symptoms in elderly people.
AB  - The present study is a retrospective study of remoxipride therapy. A total of 103
      patients, 65 years or older, with a DSM-III-R diagnosis of dementia or delirium,
      were included. They had all been treated with remoxipride because of psychotic
      symptoms or behavioural disturbances. The dose range of remoxipride was 50-300
      mg, the median dose being 75 mg. The clinical effect was rated as good in two
      thirds of the patients, and side-effects were noted in one fourth. When
      psychomotor hyperactivity was the dominating problem, a good effect was rated in
      81% of the patients. Side-effects were few and mild, the most common being
      tiredness; only 5 patients showed extrapyramidal symptoms.

PMID- 8740629
TI  - Acetylcholinesterase activity of synaptic plasma membranes during ageing: effect
      of L-acetylcarnitine.
AB  - A physiopathological role for acetylcholine (ACh) was hypothesized during ageing
      and related neurodegenerative diseases, e.g. dementia. This research was aimed to
      study acetylcholinesterase (AChE) activity during development and ageing of the
      frontal cerebral cortex of 4-, 8-, 12-, 16-, 20- and 24-month-old rats. This
      study was performed on synaptic plasma membranes, the specific subcellular
      compartment where the enzyme is located in vivo both in control animals and after
      in vivo acute treatment with L-acetylcarnitine. Maximum AChE activity was
      unaffected by age, and L-acetylcarnitine treatment increased enzyme activity in
      synaptic plasma membranes of 8-month-old rats. A comprehensive analysis of these
      results suggests: (a) the observed alterations in protein can substantially
      affect neurochemical data if results are presented as specific activities per
      unit protein; (b) energy metabolism plays the major role in the disturbed ACh
      metabolism during ageing and (c) the understanding of the mode of action of L
      acetylcarnitine in treatment of dementia.

PMID- 8740630
TI  - Dementia of the frontal lobe type: report of the neuroimaging and
      neuropsychological results of a case study.
AB  - We report the behavioural abnormalities, neuroimaging, and neuropsychological
      results of a 62-year-old patient, i.p., who shows a clinical profile that fulfils
      all characteristics of dementia of frontal lobe type. The patient has been
      followed up over 5 years with psychometric testing. Comparing her cognitive
      profiles across examinations, her performance was substantially unchanged apart
      from behavioural disturbances and performance on frontal tasks which showed a
      progressive worsening. MRI finding evidenced marked ventricular enlargement,
      prevalent frontal atrophy and hypertrophy of the genus of corpus callosum. SPECT
      investigation showed a considerable reduction of cerebral blood flow in the
      mesial parts of the frontal lobes, in the lateral surface of the right fronto
      parietal lobe, and hypo-perfusion in the right thalamic area. The results are
      discussed with reference to the features (clinical and neuropsychological) which
      distinguish different profiles of dementia.

PMID- 8740631
TI  - Cerebral ischemia: pharmacological bases of drug therapy.
AB  - The cascade of reactions caused by ischemia in brain tissue is complex and not
      completely understood, but intensive investigation has led to convincing
      hypotheses. A disturbed calcium homeostasis and oxygen radicals seem to play a
      major role in postischemic neuronal damage. In accordance to these hypotheses
      drugs with different mechanisms of action have been developed. The aim of this
      paper is to give an overview over pathobiochemical mechanisms in cerebral
      ischemia and possibilities of pharmacological intervention.

PMID- 8740632
TI  - Apolipoprotein E genotype in the prediction of cognitive decline and dementia in
      a prospectively studied elderly population.
AB  - An increased apolipoprotein E (ApoE) type epsilon 4 allele frequency is
      associated with both sporadic and familial late-onset Alzheimer's disease (AD).
      The age of onset of disease in patients homozygous for the epsilon 4 allele
      appears to be decreased by approximately 15 years compared with E2/3 individuals.
      In order to assess the influence of this allele on both dementia and cognitive
      decline in the elderly we have determined the ApoE genotype of 150 individuals
      over the age of 75 years who have taken part in a longitudinal study.
      Homozygosity for the epsilon 4 allele was rare. Of the 2 homozygotes, 1 was
      severely demented but the other did not receive a clinical diagnosis of dementia.
      The latter individual did demonstrate marked cognitive decline over a 28-month
      period. There was a consistent association between the presence of an epsilon 4
      allele and both the clinical diagnosis of dementia and cognitive decline. These
      findings confirm a genetic heterogeneity in late-onset sporadic AD and prompt
      caution in the use of ApoE genotype to predict an elderly individual's
      susceptibility to either dementia or cognitive decline.

PMID- 8740633
TI  - Tau proteins in cerebrospinal fluid from patients with Alzheimer's disease: a
      longitudinal study.

PMID- 8740634
TI  - The immunodiagnosis of Hodgkin's disease.

PMID- 8740635
TI  - Soluble interleukin-2 receptors in patients with advanced colorectal carcinoma.
AB  - The levels of soluble interleukin-2 receptors (sIL-2R) were measured in the serum
      of 52 patients with advanced colorectal carcinoma and compared to CEA and CA 19-9
      levels. Twenty-five normal, age and sex-matched individuals served as controls.
      Seventy-five per cent of the patients had increased mean serum levels of sIL-2R
      (1539 +/- 155 U/ml), while normal controls had mean levels of 555 +/- 31 U/ml (p
      < 0.001). The relationship with hepatic or lymph nodal metastases showed no
      statistically significant difference (p = 0.34 and p = 0.47, respectively). Serum
      sIL-2R levels showed a linear correlation with CEA (p < 0.05). Patients with
      lower pretreatment sIL-2R levels (less than 1.200 U/ml) had a longer survival
      than patients with higher initial levels (more than 1.200 U/ml) (p = 0.0049). In
      conclusion, the present work shows that the serum levels of sIL-2R: a) are
      elevated in patients with advanced colorectal cancer, b) have no relationship
      with the type of metastases, c) correlate with serum CEA and d) have a prognostic
      value for survival.

PMID- 8740636
TI  - Usefulness of PSA density and PSA excess in the differential diagnosis between
      prostate cancer and benign prostatic hypertrophy.
AB  - The usefulness of PSA density (PSAD) was evaluated in relation to the volume of
      the transitional zone (PSAT) and PSA excess. With this purpose we conducted a
      study including 27 patients diagnosed as having prostatic cancer (PC) and 46
      patients with benign prostatic hypertrophy (BPH). In all of them, the PSA
      concentration in the serum was determined as well as the total prostatic volume
      and the transitional zone volume; digital rectal examination (DRE) was also
      performed. The major diagnostic efficacy was obtained with the excess of PSA
      (73%, cutoff = -13 ng/ml), followed by DRE (68%), PSAT (64%, cutoff = 0.5), PSAD
      (64%, cutoff = 0.2), and lastly PSA and ultrasonography (60%). Multivariate
      analysis (logistic regression) demonstrated PSA excess and DRE to be the best
      predictors. The model obtained by regression shows the best positive predictive
      value, and PSA excess the best negative predictive value. Consequently, PSA
      excess could be relevant in prostate cancer diagnosis.

PMID- 8740637
TI  - Is serum PSA measurement a good test for early diagnosis of prostate cancer?
      Results of a pilot study and cost analysis.
AB  - Over the last years--late 1970s to early 1990s--the incidence of prostate
      carcinoma has nearly doubled, even though many more patients die suffering from
      prostate cancer than because of it. This finding, together with the slow growth
      of this tumor and the absence of a controlled trial that would suggest a benefit
      from screening, makes early diagnosis of this disease quite questionable. On the
      other hand, it is well known that prostatic carcinoma is curable as long as it is
      intracapsular, and that there is an ever increasing encouragement to early
      detection in all diseases. The costs of screening and the difficulty in balancing
      the benefits of screening against its negative effects, such as psychological
      impact and overtreatment, must be taken into account as well. In our opinion, one
      of the advantages of early diagnosis should be that the patients' quality of life
      improves, because the stage at diagnosis and, as a result, the number of patients
      suffering from bone metastasis decrease, and unknown benign pathologies can be
      cured. These observations are not at all negligible. Our study aims to
      demonstrate that by using PSA as an initial test, the screening costs are
      reasonable and the disease incidence is just as expected.

PMID- 8740638
TI  - Preliminary clinical evaluation of free/total PSA ratio by the IMMULITE system.
AB  - The role of free (F) and complexed serum PSA is now under investigation. In the
      present study, we evaluated the clinical significance of F-PSA and F/Total (T)
      PSA ratio in a preliminary series of samples from 88 patients with prostate
      cancer (PC), 113 with benign prostatic disease (BPD), and 98 with non-prostatic
      disease (NP). We used the F-PSA and third generation T-PSA (DPC, Los Angeles,
      USA) chemiluminescent enzyme immunometric assays with the IMMULITE automated
      system. At the 10 ng/ml cutoff for T-PSA levels, we obtained a sensitivity of 83%
      with a specificity of 100% in NP and 80% in BPD. The addition of the F/T ratio-
      rather than F-PSA levels--was useful to better discriminate PC and BPD in the
      cases erroneously classified by T-PSA alone: 44/68 samples (65%) were correctly
      diagnosed. Moreover, the F/T ratio was particularly effective in the critical T
      PSA range between 4.1-9.9 ng/ml; 26/40 cases (65%) were correctly evaluated. In
      conclusion, the F/T ratio seems to be an interesting auxiliary test to T-PSA, to
      be reserved for selected cases where additional diagnostic information is
      necessary.

PMID- 8740639
TI  - Oestrogen and progesterone receptors as prognostic variables in hormonally
      treated breast cancer.
AB  - This study directly compares ER status and PgR status of primary tumour tissue
      measured by enzyme immunoassays for prediction of response to therapy and
      survival in 99 women with breast cancer treated by hormone therapy. ER and PgR
      status alone both correlated with response to therapy (p = 0.002 and p = 0.02
      respectively), time to progression (p < 0.0001 and p = 0.003 respectively) and
      survival (p < 0.001 and p = 0.01 respectively). 67% of tumours ER(+)/PgR(+)
      showed responsive or static disease compared to 25% of tumours ER(-)/PgR(-).
      Tumours of mixed phenotype (i.e. ER(+)/PgR(-) and ER(-)/PgR(+)) showed an
      intermediate response rate of 46%. Similar findings were observed when tumour
      phenotype was compared with overall survival. Combining ER and PgR allows more
      accurate prediction of clinical outcome but does not aid in selecting individual
      patients for endocrine therapy.

PMID- 8740640
TI  - Comparison of one first-generation and three second-generation methods for the
      determination of CA 125.
AB  - The monoclonal antibody OC125 (Centocor, Inc, Malvern, PA) was the basis for the
      first generation of one-step immunoradiometric assays (IRMA), used to detect the
      glycoprotein CA 125. Recently two-step IRMAs were developed: the CA 125 second
      generation assays. In these new assays the CA 125 capture antibody is the M11
      monoclonal antibody coated on a solid phase and the OC125 monoclonal antibody is
      used as tracer. We compared one first-generation radioassay and three second
      generation assays (two radioassays and one ELISA) both analytically and
      clinically. The ELISA method showed the best within-assay precision and the best
      curve fitting characteristics. In the clinical comparison, none of the
      correlations between the first-generation and second-generation methods were
      really satisfactory; however, the cutoff level of 35 U/ml was confirmed. The four
      CA 125 assays do not yield equal results. As a consequence, the evolution of CA
      125 serum concentrations during disease monitoring is not reliable when different
      determination methods are used consecutively.

PMID- 8740641
TI  - Multicentre clinical evaluation of the COBAS CORE CEA, CA 125 II and PSA tumor
      marker assays.
AB  - The aim of our study was to evaluate the clinical usefulness of the tumor markers
      CEA, CA 125 and PSA using the COBAS CORE system from Roche Diagnostic Systems.
      Our results demonstrate that determination of these markers on the COBAS CORE
      immunoassay analyser provides the performance required for routine use in
      clinical practice. The results obtained in this clinical trial validate the
      correlation with disease extension, a characteristic that defines and determines
      the clinical utility of the tumor markers. We also conclude that learning to
      operate the COBAS CORE system is simple, as is management of the system through
      the user-friendly software.

PMID- 8740642
TI  - Immunoglobulin Inhibiting Reagent: evaluation of a new method for eliminating
      spurious elevations in CA125 caused by HAMA.
AB  - Cancer therapy utilising radiolabelled murine monoclonal antibodies frequently
      leads to the production of Human Anti-Mouse Antibodies (HAMA) in the recipient.
      HAMA interferes with "sandwich" immunoassays, such as those for tumour markers,
      rendering results unreliable. Published methods for eliminating HAMA from serum
      are not suitable for use in a laboratory which is processing a large number of
      assays using an automated system. We report on the use of Immunoglobulin
      Inhibiting Reagent (IIR) in CA125 assays from recipients of intraperitoneal
      radioimmunotherapy who had spuriously elevated results due to HAMA. IIR was found
      to be comparable to the admixture of mouse serum as a way of eliminating the
      effect of HAMA. IIR is ideally suited to use with an automated assay process.

PMID- 8740643
TI  - Determination of estrogen and progesterone receptors in human breast cancer
      cytosols: a comparison between radioligand binding assay (DCC) and enzyme
      immunoassay (EIA)

PMID- 8740644
TI  - Determination of free PSA in breast cancer cytosols by IRMA.

PMID- 8740645
TI  - Combined therapy with cisplatin and interferon alpha-2b (INTRON-A) in patients
      with penile carcinoma. Analysis of 2'5' oligo (A) synthetase and circulating
      interferon.

PMID- 8740646
TI  - Comparison between interleukin-2 and interleukin-12: effects on monocyte
      functions and their possible importance in the clinical significance of
      neopterin.

PMID- 8740647
TI  - Gene transfer on its long path to therapeutic application.

PMID- 8740648
TI  - Development of retroviral vectors as safe, targeted gene delivery systems.
AB  - The transfer of genes of potential therapeutic benefit is presently being
      attempted in the clinic to treat a number of genetic and virally induced
      diseases. Many of these protocols use retroviral vectors derived from murine
      leukemia retroviruses as gene delivery systems. Although these viral delivery
      systems are well suited for this purpose, a number of their characteristics, some
      of which are discussed here, are still troublesome. Future retroviral vectors
      will incorporate nonretroviral features and will be tailored to desired needs for
      specific uses. These vectors will be safer, more efficient, and targeted in their
      delivery. Further, expression of the therapeutic genes carried will be limited to
      the specific target cell type. Some of the recent advances that have been made
      towards this goal are reviewed here.

PMID- 8740649
TI  - Strategies for cancer gene therapy using adenoviral vectors.
AB  - Modification of tumor cells using gene transfer either to enhance host immunity
      or to act directly on tumor cells is being intensively studied in animal models.
      Remarkable results have yielded to approved clinical protocols in the treatment
      of cancer patients using this approach. Several methods of gene delivery have
      been developed. This article is particularly devoted to the interest of the use
      of adenoviral vectors in the different strategies of cancer gene therapy.

PMID- 8740652
TI  - Clinical application of gene transfer.

PMID- 8740651
TI  - Liver-directed gene transfer and application to therapy.
AB  - The liver is an important and attractive target for the development of gene
      therapy strategies. Many genetic diseases are manifested in the liver, and both
      infectious and malignant diseases affect this organ. Retroviral and adenoviral
      vectors have been shown to infect hepatocytes with varying efficiently in vitro
      and in vivo. The presence of unique receptors at the cellular membrane of
      hepatocytes has stimulated the development of transfer strategies based on
      receptor targeting of vectors. The results of a first clinical trial for gene
      therapy in the liver based on ex vivo gene delivery has shown both the
      feasibility and the limits of current technology. This review discusses both
      existing vectors and strategies and prospective developments towards liver
      directed gene therapy of genetic and malignant diseases.

PMID- 8740650
TI  - Antisense oncogene and tumor suppressor gene therapy of cancer.
AB  - Rapid advances in cancer gene therapy are driven by an explosive development of
      gene transfer technology and a strong demand for seeking alternatives to
      unsatisfactory conventional cancer therapies. Discovery of the genetic basis of
      cancer has indicated that cancer is a disease of genes. Among a variety of
      approaches to gene therapy of cancer, antisense oncogene and tumor suppressor
      gene therapy of cancer are the two strategies that aim at correcting genetic
      disorders of cancer through suppression of the abnormal expression of the
      proliferative genes. The potential effectiveness of these approaches is promised
      by their precise targeting at the mechanisms of the disease. Examples of several
      preclinical studies of these types of approaches that led to the approval of
      clinical trials are reviewed. Limitation and future development of these
      approaches are also discussed.

PMID- 8740653
TI  - Can the neurotrophic hypothesis explain degeneration and loss of plasticity in
      mature and ageing autonomic nerves?
AB  - The causes of age-related degeneration in the peripheral nervous system remain
      unclear. The search for clues has focused on developmental mechanisms and
      particularly on the neurotrophic hypothesis and its principal player, nerve
      growth factor, reduced levels of which are thought to cause degeneration of some
      autonomic and central neurons in old age. Nerve growth factor may well be
      important in the mature and ageing nervous system, but recent experiments on
      sympathetic nerves in ageing rats suggest that lack of NGF is not the only
      limiting factor in neuronal growth and survival. Other candidates include
      laminin, which is bound in the extracellular matrix and may act in synergy with
      NGF to regulate neuronal maintenance and growth in maturity. Reduced, region
      specific patterns of availability of one or both of these substances may underlie
      age-related degeneration in autonomic nerves. Different combinations of these
      factors may influence particular aspects of neuronal plasticity, such as
      collateral sprouting and regeneration. In addition to extrinsic factors, it
      appears increasingly likely that altered neuronal responsiveness to neurotrophic
      factors in old age contributes to structural and functional deficits in autonomic
      nerves.

PMID- 8740654
TI  - Renal neural response to ischemic renal failure in chronic hypoxic rats.
AB  - This report was designed to assess response of the renal nerve activity (RNA)
      during and after renal ischemia in chronic hypoxic rats. Hypoxia was induced by
      placing the female Wistar rats in an altitude chamber set at 5500 m for 4 weeks.
      Simultaneous recordings of left renal efferent (RENA) and afferent (RANA) nerve
      activity were performed in each pentobarbital-anesthetized rat throughout the
      experiment. Ischemic renal failure was induced by complete occlusion of the left
      renal artery for 45 min. During renal arterial occlusion (RAO), RENA gradually
      decreased while RANA enhanced initially and then this decreased gradually in both
      sea level (SL) controls and chronic hypoxic (high-altitude; HA) rats. During 45
      min of reperfusion, RENA depressed more in comparison with RANA in both groups of
      animals. In addition, RANA returned to baseline level in SL rats, while it
      remained elevated in HA rats. In the second experiment, six groups of renal
      ischemic rats were challenged by rapid intravenous infusion of 10 ml of saline,
      and urine was collected for 90 min from the left ureter. Baseline RENA was low in
      rats 4 h after RAO of SL (4SL) and of HA (4HA) groups. The effects of saline
      loading on RENA and RANA were different in HA and SL rats. Saline loading
      significantly decreased RENA but increased RANA more in SL rats. Following saline
      loading, RENA in 4SL and 4HA rats, as well as animals 24 h after RAO of SL (24SL)
      and HA (24HA) were comparable to their respective SL or HA animals. In 4SL rats,
      RANA was significantly enhanced, and remained elevated during saline loading and
      the recovery period. In 4HA, 24HA and 24SL rats, RANA reduced significantly
      during saline loading, then its activity returned to the baseline value. The
      insulted kidneys showed increased renal excretion of water and sodium in 4SL and
      4HA rats. Urinary excretion reduced significantly in 24SL rats but was almost
      normal in 24HA rats. These results indicate that a decrease in RENA may play a
      protective role in response to renal ischemia in both SL and HA rats. In response
      to renal ischemia and saline loading, different alterations of RANA in SL and HA
      rats may reflect a beneficial mechanism located in the hypoxia-pretreated kidney.

PMID- 8740655
TI  - Power spectral analysis of heart-rate variability reflects the level of cardiac
      autonomic activity in rabbits.
AB  - Power spectral analysis of heart rate (HR) variability was tested in conscious
      rabbits to assess the reliability of this method for assessing cardiac autonomic
      function in normal rabbits under resting conditions. Evaluation of power spectrum
      was performed in 5 rabbits under normal resting conditions and after sympathetic,
      parasympathetic and combined sympathetic plus parasympathetic blockade. Rabbits
      were randomly assigned to undergo sympathetic (propranolol) or parasympathetic
      (methscopolamine) blockade at the initial step followed by combined blockade. The
      power spectrum of heart-rate variability in rabbits was presented as one broad
      spectral component at frequencies mainly between 0 and 0.5 Hz. This component was
      considerably modulated by both sympathetic and parasympathetic influences with
      substantial overlap of sympathetic- and parasympathetic-related components of the
      spectrogram. Nevertheless, it was clearly shown that power of heart-rate
      variability at frequencies from 0.4373 Hz to 0.5625 Hz was determined only by
      parasympathetic influences, and sympathetic modulation of HR was presented mainly
      at frequencies from 0.0625 Hz to 0.1875 Hz. Spectral subcomponent analysis of the
      power spectrum of HR variability may be useful to follow changes in cardiac
      autonomic function in rabbits.

PMID- 8740656
TI  - Association of substance P and its receptor with efferent neurons projecting to
      the greater curvature of the rat stomach.
AB  - Retrograde tracing and immunocytochemistry were used to identify and map the
      distribution of substance P (SP) and its receptor (NK-1r) associated with gastric
      motor neurons in the dorsal motor nucleus of the vagus (DMV) in the rat brain
      stem. The presence of peptide and receptor in surrounding regions within the
      dorsal vagal complex were also observed. Injection of the retrograde tracer
      Fluorogold (FG) into the greater curvature of the stomach produced bilateral
      labelling of neurons within the DMV. The majority of the NK-1r immunoreactivity
      appeared as an intricate lattice of fibres with a small number of immunoreactive
      cell bodies. The NK-1r-labelled fibres were detected within the DMV in close
      association with FG-labelled neurons and in the region between the DMV and
      nucleus of the solitary tract (NTS). A proportion of FG-labelled neuronal cell
      bodies were also labelled with NK-1r (7% of total). The greatest density of NK-1r
      labelled fibres was observed at the rostral end of the FG-labelled neuron columns
      in the DMV (close to the IV ventricle) in the region where gastric vagal
      afferents terminate. Little NK-1r labelling was observed at the caudal end of the
      FG-labelled neuron tracts adjacent to the central canal. In the coronal plane,
      the NK-1r-labelled fibres were seen at the edges of the DMV extending into
      overlying NTS. Substance P was visualized as a dense network of fibres spanning
      the entire length of the DMV and in close association with FG-labelled neurons.
      Substance P staining was also detected in the NTS and in the ventral AP. Most of
      the association between SP/NK-1r immunoreactive fibres was observed within the
      DMV and at the border between the DMV and NTS. These findings suggest that SP
      directly regulates a subpopulation of efferent neurons in the DMV which project
      to the greater curvature of stomach.

PMID- 8740657
TI  - Tyrosine hydroxylase- and nitric oxide synthase-immunoreactive nerve fibers in
      mitral valve of young adult and aged Fischer 344 rats.
AB  - Using confocal fluorescence microscopy we studied, in whole mounts of heart
      mitral valves of young adult and aged Fischer 344 rats, the distribution of
      nerves containing the catecholamine marker tyrosine hydroxylase (TH) or the
      synthetic enzyme marker for nitric oxide, nitric oxide synthase (NOS). TH-IR was
      localized in two separate nerve plexuses which do not intermingle. The 'major'
      plexus arose from the annulus region, traversed the basal zone of the valve, and
      ramified in the intermediate zone to form a dense network of fine fibers. The
      'minor' plexus was restricted to the distal zone and originated from bundles that
      ascended the chordae tendineae to enter the valve cusp. A concentric zone located
      between the major and minor plexuses was devoid of TH-IR nerve fibers. Both
      plexuses demonstrated (i) nerves that contained numerous varicosities along the
      length of each fiber, (ii) many terminal axons and (iii) different shaped
      terminal axon endings. With age, the density of TH-IR innervation in the mitral
      valve was markedly reduced; and nerve fibers of the minor plexus were limited to
      the chordae tendinae, without extending into the valve cusp itself. NOS-IR fibers
      in the mitral valve formed a loose network that extended from the annulus to more
      than halfway down the cusp. The varicose beads of the terminal NOS-IR axons
      appeared to become progressively smaller and less intensely fluorescent until
      they disappeared at the terminal endings, which showed no specializations. No NOS
      IR fibers were observed in the distal zone of the valve leaflet or in the
      chordae. In the aged mitral valve, the density of NOS-IR nerves was decreased, as
      compared with NOS-IR innervation in the young adult valve. The existence of TH
      and NOS as well as other signal molecule markers in heart valve nerves and the
      disparate patterns of their distribution and localization provide evidence
      supporting the theory that heart valve nerves form a complex reflexogenic control
      system in the mitral heart valve. In summary, two distinct neural architectures
      are described for TH-IR and NOS-IR valve nerves, respectively. The former are
      believed to be axons dedicated to sympathetic motor functions. The NOS-IR valve
      nerves may have sensory and/or postganglionic parasympathetic motor functions. An
      implication of these findings is that different, but perhaps related, valve
      functions may be mediated by separate, dedicated circuits.

PMID- 8740658
TI  - Effects of water ingestion on gastric electrical activity and heart-rate
      variability in healthy human subjects.
AB  - Electrogastrography (EGG) is a method to record electrical activity of the
      stomach using cutaneous electrodes. Power ratio (PR) is one of the parameters and
      means the relative change of EGG power of gastric activity from before to after
      certain stimulations (e.g., meals, water or drugs). Autonomic nervous function is
      an important modulator of gastric activity, but its relation with the EGG
      parameters has not been well clarified. We recorded EGG and the R-R interval
      simultaneously both before and after drinking 150 ml water for 400 s, and
      spectrally analyzed them using the maximum entropy method in 12 healthy
      volunteers. We calculated PR from before to after water ingestion, and the power
      of the high-frequency component of R-R interval variability before (pre-HF) and
      after water ingestion (post-HF), and their ratio (rHF = post-HF/pre-HF). PR was
      positively correlated with rHR (r = 0.727; P < 0.05) and negatively correlated
      with pre-HF (r = 0.706; P < 0.05), and rHF was negatively correlated with pre-HF
      (r = 0.776; P < 0.05). These results suggest that simultaneous recording of EGG
      and ECG for frequency domain analysis is necessary to estimate the vagal nervous
      activity.

PMID- 8740659
TI  - Localization of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d)
      activity in the gastrointestinal sphincters in the guinea pig.
AB  - The distribution of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH
      d), a marker for nitric oxide synthase (NOS), in the nerves of gastrointestinal
      sphincters in guinea pigs was investigated to throw some light on the role of
      nitric oxide (NO) in these sphincteric regions. The nerve fibres with NADPH-d
      activity were observed chiefly in the circular muscle layer of the wall of
      gastrointestinal sphincters. Compared with the adjacent non-sphincteric regions,
      the proportions of NADPH-d positive myenteric neurons in the lower esophageal
      sphincter (LES), pyloric sphincter (PS) and internal anal sphincter (IAS) were
      higher (P < 0.05). The densities of NADPH-d-positive fibres in the circular
      muscle of above sphincteric regions were also higher (in LES P < 0.01; in PS and
      IAS P < 0.05). Within the circular muscle of LES, some discrete NADPH-d-positive
      intrinsic nerve cell bodies, usually smaller than their outlying myenteric
      neurons, were also observed. The dense distribution of NADPH-d-positive fibres
      within the circular muscles of gastrointestinal sphincteric regions suggests that
      NO, as a non-adrenergic non-cholinergic (NANC) inhibitory neurotransmitter, might
      play an important role in the neuronal regulation of the guinea-pig
      gastrointestinal sphincters.

PMID- 8740660
TI  - Acrylamide-induced neuropathic changes in rat enteric nerves: similarities with
      effects of streptozotocin-diabetes.
AB  - The effect of acrylamide intoxication (a widely used model for autonomic
      neuropathy) on the fluorescence intensity and density of catecholamine- and
      peptide-containing nerve fibres and tissue content of noradrenaline and the
      peptides vasoactive intestinal polypeptide, calcitonin gene-related peptide,
      substance P and neuropeptide Y in the enteric nerves of rat ileum was examined.
      Histochemical and immunohistochemical techniques were used to localize
      catecholamine- and peptide-containing nerve fibres. The tissue content of
      noradrenaline was measured using high-performance liquid chromatography, and an
      enzyme-linked immunosorbent assay technique was used to determine the tissue
      content of the peptides investigated. Acrylamide intoxication caused a
      significant decrease in the density of catecholamine-containing nerve fibres and
      tissue content of noradrenaline in the myenteric plexus of rat ileum. A decrease
      in tissue content and immunoreactivity of calcitonin gene-related peptide and an
      increase in vasoactive intestinal polypeptide was seen in the myenteric plexus of
      ileum from acrylamide-intoxicated rats. In the submucous plexus, the acrylamide
      treatment caused a decrease in calcitonin gene-related peptide immunoreactivity
      and an increase in vasoactive intestinal polypeptide and neuropeptide Y
      immunoreactivity. There was no change in either tissue content or
      immunoreactivity of substance P in both myenteric and submucous plexuses of the
      treated rat ileum. These changes have a striking similarity with those found in
      the enteric nerves of streptozotocin-diabetic rat ileum, suggesting the possible
      presence of an underlying common mechanism(s) in the development of neuropathic
      changes in the autonomic nerves of acrylamide-intoxicated and streptozotocin
      diabetic rats.

PMID- 8740661
TI  - Neuro-muscular junctions of longitudinal and circular muscle fibers of the guinea
      pig esophagus and their relation to myenteric plexus.
AB  - The structure of the neuromuscular junctions (NMJs) and their relation to the
      myenteric plexus were studied by zinc iodide-osmic acid (ZIO) staining and by
      scanning electron microscopy in the guinea-pig esophagus. The esophageal muscle
      coat consisted of the inner circular and outer longitudinal striated muscle
      fibers. The myenteric plexus was located between the two muscle layers along its
      whole length and was characterized by a loose and irregular network. It was
      demonstrated that unmyelinated nerve fibers form NMJs with the muscle fibers of
      both layers. The NMJs in the longitudinal muscle can be classified as 'plate'
      type, whereas those of the circular muscle resemble the 'grape' type. The
      different NMJs in the two muscle layers probably correspond to different
      contractile properties. The whole-mount preparations with ZIO staining also
      demonstrated that some NMJs receive minute branches from the myenteric plexus.
      Therefore, it is likely that the myenteric plexus is involved in the control of
      striated muscles of the guinea-pig esophagus.

PMID- 8740662
TI  - Sympathetic skin response and regeneration of sudomotor fibers after complete
      division of peripheral nerves.
AB  - Sympathetic skin responses (SSRs) were studied in hands of patients during
      regeneration of their median or ulnar nerves following complete severance and
      suture. The SSRs were elicited with electrical stimuli presented to the forearm
      of the normal side and recorded between the dorsum of the hand and three sites in
      the innervation area of the two nerves. The amplitude and area of the SSRs were
      compared to those obtained at the identical points on the uninjured hand. The
      responses were followed up for 16 months at 1-1.5-month intervals in a group of 6
      adults and for 14 months at monthly intervals in 7 children. After an initial
      absence, the SSRs appeared after about 4 months postoperatively at the most
      proximal site in the adults and 2-3 months in the children. It progressed
      subsequently over a 14- or 16-month observation period to less than 50% of the
      normal side in the adults and to close to 100% in children, fastest and most
      complete for the proximal recording site, considerably earlier in the children.
      End-stage recovery studied in another group of 14 adults and 7 children 2-7 years
      postoperatively reached an average of 80-100% at the most proximal recording site
      in most adults and children. The intermediate and the distal sites showed less
      complete return of the SSR. The method of recording SSRs is considered suitable
      to follow regeneration of the sudomotor fibers in the cut and sutured nerves of
      the hand.

PMID- 8740663
TI  - Isolation of synaptosomes from the rat urinary bladder.
AB  - Synaptosomes are nerve-end particles (NEP) isolated by using the technique of
      differential centrifugation. The synaptosome offers a good model for biochemical
      and pharmacological studies of the nerve endings. No report has been made on
      synaptosome isolation from the urinary bladder. The purpose of our work was to
      develop the use of synaptosome in the research of neurophysiology and
      neuropharmacology of the urinary bladder. Synaptosome-rich fraction was prepared
      from tissue homogenate of male Wistar rat urinary bladder by differential
      centrifugation (1000, 17,000 and 100,000 g) with discontinuous sucrose gradient.
      Electron microscopy showed synaptosomes as thin-walled bags containing a large
      number of synaptic vesicles. Two types of synaptosomes were easily discerned:
      those containing small agranular vesicles, and those containing dense-cored
      vesicles. The acetylcholine, norepinephrine, epinephrine and dopamine contents in
      the preparation were measured by the method of high-performance liquid
      chromatography. The respective concentrations were 300.4 +/- 30.1, 962.8 +/-
      58.5, 617.3 +/- 59.8 and 1354.8 +/- 144.2 pmol/mg synaptosomal protein. In
      conclusion, it has been demonstrated that synaptosome-rich fractions can be
      prepared from the rat urinary bladder. Thus it is possible to apply this
      methodology for the investigation of the neurobiology of urinary bladders.

PMID- 8740664
TI  - Development of NOS-containing neuronal somata in the rat kidney.
AB  - An investigation of the changes in size, number and distribution of NOS
      containing neuronal somata in the rat kidney was undertaken. The immunoperoxidase
      method for the staining of NOS and the histochemical method for the demonstration
      of NADPH-d were applied to serial thick sections (100 microns) of whole kidneys.
      Animals at embryonic day 14 (ED14), ED16, ED18, ED20, at birth (PD0), and at
      postnatal days 4 (PD4), PD12, PD21 and PD35 were studied. NOS-containing neuronal
      somata were observed by the 20th day of gestation in some kidneys and were
      consistently seen at birth. They were usually seen in groups of separated
      neuronal somata or in tight clusters. The neuronal somata were often attached or
      embedded in nerve bundles. As the kidney developed, the number of neuronal somata
      separated from each other increased, while the number of clusters remained
      relatively constant. The size of the neuronal somata increased with development.
      There were highly significant statistical differences in the size of the neuronal
      somata between all groups, except between PD12 and PD21. The distribution of
      neuronal somata at birth was similar to that of the adult. They could be found,
      (a) at the free renal pelvic wall; (b) in the connective tissue at the angular
      space between the renal pelvis and the renal parenchyma (SPP); and (c) along the
      interlobar vessels. At birth and in the early stages of development, the greatest
      number of neuronal somata were located at the renal pelvis. In the later stages
      of development, more neuronal somata appear in the connective tissue between the
      renal pelvis and the renal parenchyma. The location of NOS-containing neuronal
      somata suggests that they might have a modulatory role on the sympathetic and
      sensory renal nerves all through development.

PMID- 8740665
TI  - Sensory nerves play an efferent role in the function of the arterioles, but not
      the dilator muscle, of the rat iris.
AB  - We have studied the expression, distribution and function of receptors for the
      sensory neurotransmitters, substance P (SP) and calcitonin gene-related peptide
      (CGRP) in the dilator muscle and arterioles of the rat iris. Immunohistochemical
      studies showed that the sensory fibres containing these peptides are distributed
      throughout the connective tissue stroma of the iris and in association with the
      larger arterioles, but do not come into close association with the dilator muscle
      cells. Using reverse-transcription polymerase chain reaction, we have shown that
      both NK1 and NK3 receptor message is expressed by iris tissue, comprising both
      dilator muscle and stromal tissue. Binding sites for the NK1 agonist, [Sar9,
      Met(O2)11]-substance P (SarSP), and for CGRP are confined to the stromal layer
      and to the larger arterioles within that layer and do not appear to be associated
      with the dilator muscle itself. Application of either SarSP or CGRP produced both
      a vasodilatation and an inhibition of sympathetic nerve-induced vasoconstriction
      of the larger arterioles. Neither SarSP nor CGRP altered the resting tone of the
      dilator nor were they capable of modulating the contractions due to sympathetic
      nervous activity. These results suggest that the sensory fibres perform an
      efferent role in the larger irideal arterioles while their presence in the
      irideal stroma appears not to modulate the activity of the dilator muscle.

PMID- 8740666
TI  - Segmental distribution of afferent neurons innervating the canine testis.
AB  - To clarify the afferent innervation of the canine scrotal contents, retrograde
      labeling of neurons in the dorsal root ganglia (DRG) has been carried out using
      two methods: (1) horseradish peroxidase (HRP) injection into the surface of the
      testis and epididymis; and (2) exposure of the superior spermatic nerve to a
      fluorescent dye (Fast blue; FB). Injections of HRP resulted in labeling of DRG
      cells located predominantly from T10 to L4 (87%) and, to a lesser extent, at S1
      S3 (13%). Transection of the vas deferens previous to testicular injections
      eliminated labeling in the S1-S3 DRG, but not at thoracolumbar levels. These
      findings indicated that primary afferent fibers of the testis and epididymis
      project mainly to the DRG at higher than L4 through the superior spermatic nerve,
      but an additional population of the fibers also projects the sacral level through
      the inferior spermatic nerve. Exposure of the superior spermatic nerve to FB
      resulted in a similar distribution of labeled cells as compared with testicular
      injections of HRP after vasectomy. Labeled cells (8.1%) were also observed in the
      contralateral T13-L3 DRG. In both FB and HRP groups, the major part of the
      labeled cells was located in L1 and L2. The sizes of HRP- and FB-labeled cells
      were smaller than those of unlabeled cells in the L1 and L2 DRG. The cumulative
      frequency distribution histogram for the diameter of HRP- and FB-labeled cells
      could be fitted by a normal distribution.

PMID- 8740667
TI  - Nitroxidergic innervation of guinea pig cerebral arteries.
AB  - The presence and distribution of nitric oxide synthase (NOS)-immunoreactive nerve
      fibers associated with the guinea pig major cerebral arteries was studied by
      means of immunohistochemical, histochemical and ultrastructural techniques.
      Anterior arteries of the circle of Willis received a rich supply of perivascular
      nerve fibers containing NOS immunoreactivity while posteriorly localized arteries
      presented a moderate to sparse innervation. A double immunofluorescence staining
      technique revealed that NOS was localized in nerve fibers distinct from those
      displaying substance P or tyrosine hydroxylase. Combined immunofluorescence and
      histochemical staining of the same preparation indicated that NOS
      immunoreactivity was localized in putative cholinergic nerve fibers (identified
      by their acetylcholinesterase content) and that NADPH-diaphorase activity (a
      marker for NOS-containing neurons) was found in nerves which also possessed VIP
      immunoreactivity. The ultrastructural study revealed that NOS immunoreactivity
      was present in numerous nerve varicosities at the adventitial-medial border.
      These results suggest that NO and VIP co-exist in putative parasympathetic nerve
      fibers supplying the guinea pig cerebral arteries and may be release together in
      response to nervous stimulation.

PMID- 8740668
TI  - Effect of metoclopramide on muscle sympathetic nerve activity in humans.
AB  - The aim of this study was to determine the effect of metoclopramide on the
      sympathetic nervous system. Muscle sympathetic nerve activity was increased in
      two stages after metoclopramide injection. The initial increase in sympathetic
      nerve activity may result from the unloading of arterial baroreceptors because
      there was a negative correlation between mean blood pressure and muscle
      sympathetic nerve activity. The later increase in muscle sympathetic nerve
      activity may be attributed to the central activation of the sympathetic nervous
      system because there was a positive correlation between mean blood pressure and
      muscle sympathetic nerve activity. These results suggest that metoclopramide
      activates the sympathetic nervous system by two different mechanisms.

PMID- 8740669
TI  - Treatment of primary erythromelalgia with cyproheptadine.
AB  - Erythromelalgia is a rare disorder characterized by burning pain of the
      extremities associated with red discoloration and increased temperature of the
      skin. We observed the effects of several drugs on two patients with primary
      erythromelalgia. Anti-inflammatory drugs such as aspirin had no effects for their
      symptoms. The alpha-adrenergic agonist midodrine slightly reduced skin
      temperature and redness of the extremities, and minimally reduced the pain in one
      patient. The partial alpha-adrenergic agonist and 5-hydroxytryptamine (5-HT)
      agonist/antagonist dihydroergotamine transiently reduced skin temperature and
      pain to some degree in one patient. The 5-HT and histamine antagonist
      cyproheptadine effectively relieved the burning pain and increased skin
      temperature.

PMID- 8740670
TI  - The definition of orthostatic hypotension, pure autonomic failure, and multiple
      system atrophy.

PMID- 8740671
TI  - Laparoscopic cholecystectomy: 700 consecutive cases.
AB  - From March 1993 till June 1995 700 laparoscopic cholecystectomies have been
      performed on 590 female and 110 male patients who ranged form 10 to 82 years of
      age at the Departments of Surgery of County Hospital and Alexander's University
      Hospital in Sofia. Ninety seven of the patients (13.8%) who have had laparoscopic
      cholecystectomies (LC) were diagnosed as acute cholecystitis and the rest as
      chromic calculous cholecystitis. In 16 cases (2.28%) a conversion to standard
      open cholecystectomy was necessary, the most frequent causes being intraoperative
      bleeding and unsuspected preoperatively common bile duct stones. Immediate or
      early postoperative laparotomy was performed in four cases because of biloma (1),
      small intestine strangulation in the umbilical region (1), perforated duodenal
      ulcer (1), bleeding (1). One case required laparotomy and removal of a clip
      misplaced tangentially to the right hepatic duct. There were no cases with lethal
      outcome following LC. Sixty-five patients have had intraoperative cholangiography
      and 14 patients underwent concomitant laparoscopic choledochotomy and a common
      bile duct stones extraction.

PMID- 8740672
TI  - Is laparoscopic splenectomy a justified approach in hematologic disorders?
      Preliminary results of a prospective multicenter study. Belgian Group for
      Endoscopic Surgery.
AB  - The feasibility and safety of laparoscopic splenectomy were evaluated in a
      prospective multicenter study of 50 patients operated on for idiopathic
      thrombocytopenic purpura (ITP) (n = 31), hereditary spherocytosis (n = 6),
      hemolytic anemia (n = 4), Hodgkin's disease or lymphoma staging (n = 5), benign
      splenic tumors (n = 3), and wandering spleen (n = 1). Conversion to laparotomy
      was required in 10%. An accessory spleen was routinely searched for, although the
      lesser sac was opened during surgery in only 10%; the overall incidence was 14%.
      Hospital mortality was 2% and postoperative morbidity 22%. Postoperative hospital
      stay and home rehabilitation were improved when exclusively laparoscopic
      splenectomy was performed. In ITP patients, at a mean follow-up of 8.2 months, 8
      patients (27%) had recurrence of thrombocytopenia, which was transient in 7% and
      permanent in 20%. Laparoscopic splenectomy is feasible and safe when performed in
      selected patients by expert laparoscopic surgeons. Adequate selection of patients
      and routine, careful search for accessory spleen are critical. The recurrence
      rate (20%) for ITP was high at 8.2 months, and this factor is the major
      limitation of laparoscopic splenectomy at present.

PMID- 8740673
TI  - Five years of laparoscopic cholecystectomy in The Netherlands.
AB  - Since its introduction in spring 1990, laparoscopic cholecystectomy has become
      the treatment of choice for uncomplicated gallstone disease in The Netherlands.
      Several nation-wide surveys conducted by the authors show a rapid diffusion of
      this operation. 70-75% of all cholecystectomies are performed laparoscopically in
      almost all Dutch hospitals. The incidence of common bile duct lesions was
      relatively high at the beginning (1% in 1991) but declined to 0.68% at the end of
      1992. It is assumed that the incidence of these lesions will decrease further to
      a percentage comparable to that after conventional cholecystectomies of 0.5%. The
      wound related complications of 1.65% is rather low. Despite the reduction in
      operative morbidity and early resumption of full activity resumption laparoscopic
      cholecystectomy has met financial restraints, because of the budget system in The
      Netherlands. There are no incentives for surgeons, hospital management and health
      insurance companies to stimulate laparoscopic cholecystectomy. The social
      economic benefit of the operation is difficult to quantify in the current health
      care system in The Netherlands.

PMID- 8740674
TI  - Laparoscopy in the gastroesophageal junction.
AB  - Three years experience of laparoscopic surgery for treatment of gastroesophageal
      reflux, large paraesophageal hernia and morbid obesity is presented. One hundred
      and thirty-six patients with reflux esophagitis and 6 patients with large
      paraesophageal or combined hiatal hernias have been laparoscopically treated with
      hiatal hernias have been laparoscopically treated with hiatal hernia repair and a
      360 degrees Rosetti (N = 109) or semitotal Toupet (N = 33) fundoplication.
      Sixteen patients with morbid obesity have been treated with laparoscopic
      placement of a variable band around the cardia. Twelve months follow-up is
      available for 74 of the esophageal reflux patients. 90% of the patients are
      completely satisfied. One patient has been reoperated due to recurrent reflux and
      one due to hiatal fibrosis. The cardia banded patients achieved the desired
      dysphagia to control food intake. Complication rates are low in all groups.
      Laparoscopic fundoplication, closure of large hiatal defects and cardia banding
      are feasible with low morbidity and comparable outcome to open surgery. Further
      studies are needed to investigate to what extent the laparoscopic technique is
      beneficial to the patient and cost effective.

PMID- 8740675
TI  - Laparoscopic adrenalectomy.
AB  - Traditional adrenalectomy usually required long incisions that causes
      considerable pain and morbidity. Adrenal tumours are ideal for laparoscopic
      removal because they are usually small, benign and no reconstruction is needed.
      Various laparoscopic approaches have been described. Early reports of
      laparoscopic adrenalectomy described the lateral transabdominal approach. The
      extraperitoneal approach needed an artificial space to work. Our unit used the
      anterior transabdominal approach because it provided clear anatomical landmarks
      and early control of adrenal veins is possible. Initial results from various
      authors showed encouraging results. Although the operative time is longer the
      time to resume diet and mobilization is shorter when compared to open surgery. As
      experience gained, the operative time can be shortened. We believed that with
      proper preoperative assessment and preparation, laparoscopic adrenalectomy is
      safe and feasible.

PMID- 8740676
TI  - Port site metastasis. An unresolved problem in laparoscopic surgery. A review.
AB  - After the explosive success of laparoscopic cholecystectomy, great interest has
      been shown in the laparoscopic treatment of digestive malignancies. Laparoscopy
      has been proposed for diagnosis and staging, and as a technical option aiming to
      cure or palliate. But this optimism has been tempered by the doubt about the
      potential disseminatory role of laparoscopy after the observation of a large
      number of port site seeding tumors. Since the first laparoscopic cholecystectomy,
      more than 100 port site metastases have been reported, without a clear
      explanation for these findings. Port site recurrences have been observed after
      gynaecologic procedures, laparoscopic cholecystectomy in which an unsuspected
      gallbladder cancer was found and after laparoscopic operations indicated for
      oncological treatment of digestive tumors, mainly colorectal cancer. Other cases
      have been reported after thoracoscopic resection of oesophageal cancer or
      urologic cancer, even after staging laparoscopy associated with sampling.
      Possible mechanisms for port site cell implantation are direct implantation in
      the wound during unprotected and forced tissue retrieval or by contaminated
      instruments during tumor dissection, the effect of gas turbulence in long
      laparoscopic procedures and embolization of exfoliated cells during tumor
      dissection or hematogenous dissemination. Probably, a multifactorial mechanism
      may be responsible, in which the key factors could be a long operative procedure,
      the high pressure pneumoperitoneum, tumoral manipulation during dissection and
      forced extraction of unprotected specimens. Prophylactic measures proposed to
      avoid this disastrous complication are the use of protective bags for tissue
      retrieval, peritoneal lavage with heparin in order to avoid adhesion of free
      cells, or lavage with cytocidal solutions.

PMID- 8740677
TI  - Laparoscopic management of superior mesenteric artery syndrome.
AB  - Superior mesenteric artery syndrome (SMAS) is a rare clinical condition that
      should be considered in patients with long-standing abdominal complaints where
      endoscopic and conventional roentgenographical findings are often negative. It
      has been claimed that SMAS is caused by intermittent obstruction of the
      horizontal portion of the duodenum between the superior mesenteric artery and the
      spine and the aorta. The main target of this presentation is to present our
      experience in the laparoscopic management of 4 cases of documented SMAS after
      failure of medical treatment. The laparoscopic severing of the ligament of Treitz
      is a feasible and safe technique. It could bring about total relief of symptoms
      in three out of the four patients. The operative time rapidly decreased with the
      acquaintance of the field. The visualization (exposure) is quite satisfactory.
      the technique offers added precision and accuracy to the dissection manoeuvres.
      Recovery was uneventful and rapid with minimal needs for postoperative analgesia.
      We recommend the use of mini-endoshear (pediatric). Phases of dissection from the
      mesocolon and retro-pancreatically are presented. We stress the finding of the
      drainage of the inferior mesenteric vein into the superior mesenteric vein
      instead of the splenic vein. This could put the inferior mesenteric vein (looking
      as a fibrous band) in jeopardy. Also it reduces the area of access to the
      retropancreatic dissection. We raise the possibility of an etiological role of
      this anatomical variation to the duodenal compression and call upon the study of
      such a possibility. The importance to attain the proper retropancreatic space has
      been shown by the possibility of dissecting between the uncinate process and the
      rest of the pancreas. The psychological impact of a minimal invasive approach
      together with symptoms relief was quite rewarding.

PMID- 8740678
TI  - Bile duct injuries in the era of laparoscopic cholecystectomy.
AB  - By the introduction of laparoscopic cholecystectomy a new field of surgical
      development has been opened, resulting in the reduction of conventional surgical
      trauma, and giving the chance to the patient seeking for less postoperative pain,
      short hospital stay and quick return to activity and work. In spite of these
      advantages, many laparoscopic cholecystectomy related complications occurred,
      especially in the period of the learning curve. Due to the special technical
      requirements, problems of the two dimensional vision, depth perception and hand
      eye coordination guided to injuries of the bile ducts, which reached a high rate
      of 3%. This rate is ten times more when compared with conventional
      cholecystectomy. The authors present a detailed account of the causes of the
      injuries, their typical localisation and the best way to avoid and treat them.

PMID- 8740679
TI  - Laparoscopic Heller cardiomyotomy with intraoperative manometry in the management
      of oesophageal achalasia.
AB  - Results of an ongoing clinical study treating achalasia patients with
      laparoscopic Heller myotomy and Dor anterior fundoplication are presented. 18
      patients underwent surgery between August 1991 and July 1995. Completeness of
      myotomies and calibration of fundoplications were measured using intraoperative
      manometry. Only one intraoperative complication, a perforation of the mucosa
      sutured laparoscopically, was encountered. There were no surgical mortalities nor
      postoperative morbidities. Mean hospital stay was 3.4 days. Complete relief of
      dysphagia and modifications of radiological and manometric patterns were achieved
      in all patients. All patients remain asymptomatic at 2 to 48 months from surgery.
      These results compare favourably with those of traditional surgery and of
      pneumatic dilatation.

PMID- 8740680
TI  - Laparoscopic treatment of functional diseases of the esophagus.
AB  - The possibilities of laparoscopic surgery in the treatment of functional
      esophageal diseases (gastroesophageal reflux, achalasia and epiphrenic
      diverticula) are illustrated with special emphasis on the technical aspects,
      including intraoperative complications and postoperative care. Results are
      discussed on the ground of the following experience. Thirty-seven laparoscopic
      fundoplications were performed with 13% conversion rate, 2.7% postoperative
      morbidity (1 slipped Nissen requiring redo laparoscopic surgery). Median
      operative time was 140 min. One patient complained of dysphagia relieved by
      endoscopic dilation (2.7%). All patients are not asymptomatic after a median
      follow-up of 16 months although one has gastroesophageal reflux (GER) at 24-hrs
      pH monitoring. forty laparoscopic Heller-Dor procedures: 7% conversions, 5%
      postoperative morbidity. Median duration 120 min. One patient complained of
      persistent dysphagia requiring endoscopic dilation (2.5%) and asymptomatic GER
      was detected in 8% of patients. Finally, 2 patients underwent laparoscopic
      diverticulectomy, esophagomyotomy and Dor fundoplication without morbidity and
      excellent postoperative result. Laparoscopic treatment of functional diseases of
      the esophagus is safe and effective, provided it is performed by an experienced
      surgeon with respect for some important technical details. Further follow-up is
      needed to evaluate long-term results.

PMID- 8740681
TI  - The present state and future of endoscopic surgery.
AB  - The present state and future of endoscopic surgery is analyzed on the basis of
      our own experience with endoscopic methods applied in clinical practice. Data
      were obtained from 73,572 diagnostic endoscopies and 1975 surgical procedures
      performed between 1972 and 1994. A significant role of endoscopic procedures was
      observed in stomach and duodenum surgery, bile duct and pancreatic surgery and
      colorectal surgery. We performed 9100 ERCP, 1200 endoscopic sphincterotomies, 61
      bile duct prosthesis placement, 1086 cholangioscopies, 61,105 gastroscopies, 422
      endoscopic hemostasis of the upper GI tract, and 376 curative polypectomies. We
      introduced sphincter Oddi manometry, endoscopic ultrasonography and minimal
      invasive methods to surgical practice in the treatment of oesophageal, gastric
      and rectal strictures such as balloon dilation and laser recanalization. Modern
      endoscopic methods used together with ultrasonography, radiology and computer
      techniques create progress in surgery.

PMID- 8740682
TI  - Value of diagnostic laparoscopy in abdominal malignancies.
AB  - Diagnostic laparoscopy was performed in 72 patients for diagnosis of suspected
      cancer or staging of intraabdominal malignancies. In 66 of 72 patients (91.7%) a
      diagnosis was possible laparoscopically and in 53 patients (73.6%) a laparotomy
      was avoided. In 19 of 72 patients (26.4%) laparoscopy changed staging of
      preoperative non-invasive test and helped to plan proper surgical management.
      Laparoscopy has proved to be an effective diagnostic tool in abdominal
      malignancies and should help to avoid unnecessary laparotomies in case of
      incurable disease. It should be used complementary to non-invasive imaging
      methods and the addition of laparoscopic ultrasonography will improve the
      accuracy of examination.

PMID- 8740683
TI  - The role of relaparoscopy in the management of bile leaks after laparoscopic
      cholecystectomy.
AB  - The incidence of bile leaks has increased with the advent of laparoscopic
      cholecystectomy. The present paper is focused on bile leaks--their diagnosis and
      management approaches with special consideration to relaparoscopy. From February
      1992 to May 1995 a total of 1223 laparoscopic cholecystectomies were performed in
      two hospitals. Eight biliary leaks were found in the series under study (i.e.
      0.65%). The diagnosis was confirmed by means of ultrasound, CT scans and ERCP.
      Three leaks resolved spontaneously on external drains placed during the
      operation. Two and three patients underwent laparotomy and relaparoscopy,
      respectively. The etiology of the leakage included three cases of ducts of
      Luschka, one cystic duct leak, and one retained CBD stone. the source of the
      remaining leaks was not determined. In all cases the management approaches
      comprised relaparoscopy and laparotomy. It may be concluded that an early
      diagnosis and management of bile leaks after laparoscopic cholecystectomies would
      prevent further complications.

PMID- 8740684
TI  - The impact of laparoendoscopic surgery on the training of surgical residents.
AB  - Laparoscopic cholecystectomy is an accepted part of the training of surgical
      residents at present. Further procedures performed by residents include
      laparoscopic appendectomy, herniorrhaphy and others. This report analyzes the
      first 22 months of operative laparoscopy in Bakes Surgical Hospital and the
      impact on the training of residents. From September 1993 through May 1995 four
      residents performed 179 laparoscopic operations. Their operative experience has
      been shifted especially towards laparoscopic cholecystectomy but education in
      open cholecystectomy and open biliary tract procedures has not been jeopardized.
      It may be concluded that surgical residents can master essential laparoscopic
      operations without additional complications in a manner standard for training of
      other procedures.

PMID- 8740685
TI  - Bile duct injury in laparoscopic cholecystectomy.
AB  - Bile duct injuries in laparoscopic cholecystectomy are briefly reviewed. The
      Norwegian National Cholecystectomy Registry was started on April 1, 1993, to
      collect data from most Norwegian surgical departments. in the period April 1,
      1993-May 31, 1995, common bile duct (CBD) injuries necessitating treatment were
      reported in 0.61% of 2,612 laparoscopic cholecystectomies and in 0.74% of 674
      open cholecystectomies. Early diagnosis is mandatory and the treatment is then
      simple. Delayed diagnosis is dangerous and the treatment may then be difficult.
      This field seems to show a difference between publications and the real world.

PMID- 8740686
TI  - Laparoscopic treatment of acute biliary pancreatitis.
AB  - Laparoscopic cholecystectomy (LC) has become the standard treatment of
      gallstones. Application of LC in certain complications of biliary stones such as
      acute biliary pancreatitis (ABP) is not well defined. 10-30% of patients with ABP
      present associated bile duct stones, and the realization of a preoperative ERCP
      has been routinely proposed. Nevertheless, this examination may be unnecessary in
      most patients. AIM: To investigate the applicability of laparoscopic surgery for
      treatment of ABP. MATERIALS AND METHODS: Between Jan-1992 and June-1995, 368
      patients were prospectively evaluated for LC, 274 for indications other than ABP.
      (Group I, LC) and 91 as a consequence of ABP. (Group II, ABPxL). ERCP was
      indicated when ultrasonography showed a dilated bile duct (> 8 mm) or when the
      liver function test (LFT) presented high scores. Age, sex, operative time,
      incidence of bile duct stones, postoperative stay and morbimortality were
      evaluated. RESULTS: The two groups were well matched for age, sex and associated
      medical risk factors. There were no differences in the operative time, conversion
      rate or postoperative morbidity (10% vs 10%). ERCP was performed in 25 patients
      in Group II and bile duct stones were found in 12 cases. In all cases an
      intraoperative cholangiography was performed, and in 6 patients, bile duct stones
      were removed by laparoscopic means. Three patients were converted to open surgery
      on finding duct stones which could not be treated by laparoscopic means. Mean
      postoperative stay was significantly longer in Group II than in Group I. In two
      cases, pancreatic pseudocyst was attempted with a laparoscopic approach.
      CONCLUSIONS: Definitive treatment of ABP could be accomplished effectively by
      laparoscopy, with selective indication of ERCP.

PMID- 8740687
TI  - Training and credentialling for laparoscopic surgery in the developing world.

PMID- 8740688
TI  - Laparoscopic surgery in the developing world. An overview of the Indian scene.
AB  - We present experience of laparoscopic surgery commencing in 1972 with diagnostic
      laparoscopy in a Surgical Unit in Bombay. By 1990 we had completed 2800
      diagnostic laparoscopies with no mortality, 0.08% complication rate, 85% positive
      diagnosis and an instrument cost of about Rs. 35 (US $ 1.2) per patient. We have
      over the past 5 years performed 890 laparoscopic cholecystectomies (LC) with no
      mortality, no blood transfusion, and one CBD injury. With reusable equipment,
      monopolar diathermy and selective cholangiography, LC is cost-efficient in a
      developing country. Over this period over 60 laparoscopic appendectomies were
      performed, with the use of catgut ligatures and self-made endo-loops.
      laparoscopic appendectomy is cost-effective under our conditions. We have done 46
      hernia repairs, and by contrast find it far more expensive and with inferior
      results to standard hernia repair. Advanced laparoscopy for ulcer and reflux
      disease, bowel resection, retroperitoneal and thoracic laparoscopy are being
      given a trial in several centres in the developing world.

PMID- 8740689
TI  - Esophageal achalasia: laparoscopic Heller cardiomyotomy.
AB  - A laparoscopic Heller cardiomyotomy technique was used on five patients whose
      esophageal achalasia was diagnosed clinically, radiologically manometrically. The
      physiological principles and operational steps are the same as in open surgery.
      with the patient in an anti-Trendelenburg 30 degrees position and the surgeon
      between the patient's legs, a CO2 pneumoperitoneum was produced. Five trocars
      were used. the esophagus was freed by blunt dissection and an 8 cm longitudinal
      myotomy was made on the anterior surface of the thoracic esophagus starting a few
      centimetres above the cardias and parallel and to the left of the anterior vagus,
      the magnified operative field facilitated more precise myotomy. The myotomy
      incision ended 2 cm from the esophageal-gastric junction. We closed the angle of
      His before performing a Dor anterior fundoplication with anchorages to the
      diaphragmatic crura. Mean operation time was 2 hrs 45 min. Intraoperative blood
      loss was less than 100 ml. In comparison with open-surgery, patients had less
      postoperative pain, needed only non-narcotic analgesics for the first 12 hrs, and
      had no unsightly operation scar. patients tolerated liquids between 24 and 48
      hrs. Hospitalization time was 3 to 5 days. Long-term follow-up transit studies,
      manometry, and 24 hrs pH measurements are needed to fully evaluate the technique.
      At two months, the symptoms of dysphagia had completely disappeared in three
      patients: the results were qualified as excellent. As some dysphagia for solids
      remained in the other two, they were qualified as good.

PMID- 8740690
TI  - Laparoscopic treatment of gastro-esophageal reflux disease: indications and
      results.
AB  - This paper deals with the indications, techniques and results of laparoscopic
      total or partial posterior fundoplications (Nissen and Toupet procedures,
      respectively) performed in 41 patients with gastroesophageal reflux disease
      (GERD) failing to respond to medical treatment. Stationary manometry and 24-hour
      esophageal pH monitoring established the indications for surgery. Laparoscopy was
      attempted in all patients, even when giant mixed or para-esophageal herniations
      were present. The rate of conversion to laparotomy amounted to 12.2%. There were
      no intraoperative complications. Major complications were observed in 3 patients
      (8%) and included 2 cases of slipped Nissen and 1 of pneumonia. Four patients had
      persistent postoperative dysphagia; two of them were re-operated and two were
      treated with pneumatic dilatation. Reflux only recurred in 1 patient. Functional
      follow-p demonstrated an overall increase in LES resting pressure and length,
      with no abnormal gastro-esophageal reflux episodes, findings which tended to
      persist in the long term.

PMID- 8740691
TI  - Living with the syndrome.

PMID- 8740692
TI  - Analysis of phosducin as a candidate gene for retinopathies.
AB  - Phosducin, a retina-expressed gene mapped to chromosome 1q25-32.1, was analyzed
      as a candidate gene for retinopathies. The phosducin gene was cloned and
      characterized, and PCR primers were designed. Eighty-three patients with various
      retinopathies and 45 control subjects (24 American, 21 Japanese) were analyzed
      for mutations in the phosducin gene by PCR, denaturing gradient gel
      electrophoresis (DGGE), and sequencing. A heterozygous sequence variant changing
      a glycine to arginine at codon 178 was found in one Usher syndrome type II (USH2)
      patient, while the other USH2 patients did not show any coding sequence variant.
      A heterozygous sequence variant changing an asparagine to lysine at codon 174 was
      found in a patient with a severe retinal degeneration in the category of diseases
      known as acute zonal occult outer retinopathy (AZOOR). Three non-coding sequence
      variants were found. Two of these were always present together and found in 20.8%
      of American and 2.4% of Japanese control subjects, reflecting a difference in
      population pools. In conclusion, the phosducin gene did not show mutations
      consistent with it being the causative gene for USH2, but its possible
      pathogenicity in AZOOR or other retinopathies remains an open question which may
      be answered by further analysis.

PMID- 8740693
TI  - Ocular findings in 55 patients with Down's syndrome.
AB  - Fifty-five patients with Down's syndrome were examined to evaluate the
      characteristics and frequency of ocular findings. Of these patients, 29 (52.7%)
      were hypermetropes, 7 (12.7%) were emmetropes, and 7 (12.7%) were myopes;
      astigmatism of more than 3.00 diopters was present in 7(12.7%) patients.
      Strabismus was observed in 12 (21.8%) patients. All but one of these 12 patients
      also had esotropia. Congenital nasolacrimal duct obstruction was present in 12
      subjects (21.8%). Blepharitis was found in 19 (34.5%) cases. Nystagmus occurred
      in 7 (12.7%) patients. Brushfield spots were detected in only 20 (36.3%) of the
      patients and were more common in light-colored irides. Lens opacities were
      diagnosed in 11 (20%) patients, and two underwent successful cataract surgery. On
      fundus examination, an increased number of retinal vessels crossing the optic
      nerve head was detected in 21 (38.1%) cases. One of the patients had a retinal
      detachment. Significant but correctable ocular problems are present in patients
      with Down's syndrome and may interfere with the quality of life of the patient
      and with binocular vision. Surgical intervention may be needed for strabismus and
      for cataracts.

PMID- 8740694
TI  - Retinoblastoma in Turkey: diagnosis and clinical characteristics.
AB  - Retinoblastoma (RB) is the most frequent malignant intraocular tumor in
      childhood. Six hundred and thirty-six cases with 831 RB-affected eyes were
      diagnosed and treated in our specialist center between 1963-1994. The diagnosis
      was made by histopathologic examination in 617 cases and clinically in 19 cases.
      Four hundred and forty-one (69.3%) cases were unilateral and 195 (30.7%) were
      bilateral. Two hundred and sixty-eight (42.1%) were females and 368 (57.9%) were
      males. The youngest patient was 20 days old and the oldest was 16 years old at
      the time of diagnosis (mean: 2.2 years). In thirty-four (5.3%) cases, a family
      history of RB was present. Ten of these cases were unilateral and 24 were
      bilateral. The most frequent presenting signs were leukocoria (394 cases, 61.9%),
      buphthalmos (92 cases, 14.5%), and strabismus (68 cases, 10.7%). The referring
      initial diagnoses were correct in 519 (81.6%) cases and false-negative in 117
      (18.4%) cases. The most frequent initial false-negative diagnoses of the
      referring physicians were buphthalmos (43 cases, 6.8%), endophthalmitis (37
      cases, 5.8%), and retinal detachment (12 cases, 1.9%). Apart from these 636
      cases, there were 29 false-positive RB diagnoses during the same study period for
      which enucleation was performed. False-positive diagnoses included
      endophthalmitis (9 cases), retinal dysplasia (6 cases), retinal detachment (5
      cases), vitreous hemorrhage (4 cases), Coats' disease (4 cases), and toxocariasis
      (one case). Ancillary testing for metastasis was carried out in all cases with
      newly diagnosed retinoblastoma. Five hundred and ninety-eight (72%) eyes had
      intraocular disease and 233 (28%) had extraocular spread. Of these 233 RBS, 58
      had systemic disease. Fifty-two out of 58 tumors showing systemic involvement had
      either optic nerve or extrascleral extension at the histopathologic examination
      of enucleation material. The remaining six eyes had intraocular Class IV-V RB.

PMID- 8740695
TI  - Clinical and genetic aspects of two Spanish families with autosomal dominant
      retinitis pigmentosa (ADRP)
AB  - A study was made of two families with autosomal dominant retinitis pigmentosa
      (ADRP) from Valencia (Spain). One family (ADRP15) was found to have mutation in
      codon 114 of the rhodopsin gene that led to a substitution of a glycine for an
      aspartic acid. The second family (ADRP7) substituted an aspartic acid for valine
      in codon 173 of the peripherin-RDS gene. Rhodopsin is involved in 25% of ADRP
      cases and many mutations of this gene have been described as causing different
      forms of the disease, with variable severity and age at onset. ADRP has been
      classified as RP with a milder symptom evolution, a typical RP fundus pattern,
      and macular involvement occurring after the second decade of life. Peripherin-RDS
      gene mutations lead to RP or other retinopathies. Furthermore, two mutations in
      codon 172 have been described as causing macular dystrophy. In ADRP7, a mutation
      in neighboring codon 173 produced RP with an atypical fundus pattern and macular
      involvement within the first decade of life. These observations confirm the
      established clinical and genetic heterogeneity involved in this form of RP.

PMID- 8740696
TI  - Congenital hereditary autosomal recessive alacrima.
AB  - This report describes two phenotypically normal sisters, each married to a
      phenotypically normal paternal cousin. One couple had one female and one male
      child with alacrima; the other couple had a similarly affected girl. The
      keratitis sicca was manifested by punctate staining of the conjunctiva and
      blotchy staining of the cornea in the interpalpebral zone with fluorescein and
      Rose Bengal. Apart from an associated atopy in one of the children,
      pharmacological testing, biochemical analysis, and clinical examination suggested
      dysfunction of the lacrimal glands. We propose that the alacrima in this family
      is inherited in an autosomal recessive fashion.

PMID- 8740697
TI  - Familial uveal melanoma: absence of germline mutations involving the cyclin
      dependent kinase-4 inhibitor gene (p16).

PMID- 8740698
TI  - Immunohistochemical characterization of canine transmissible venereal tumor.
AB  - The collective immunohistochemical expression of human lysozyme, human alpha-1
      antitrypsin, human CD3 antigen, calf vimentin, human keratins, human lambda light
      chains,canine immunoglobulins IgG, IgM, and bovine protein S-100 has been
      analyzed on formalin-fixed, paraffin-embedded tissue sections of 25 spontaneous
      canine transmissible venereal tumors (CTVT) from both genital and extragenital
      locations using the avidin-biotin-peroxidase complex technique. Lysozyme
      immunoreactivity was detected in 10/25 CTVT, alpha-1-antitrypsin in 14/25 CTVT,
      and vimentin in 25/25 CTVT. All CTVT cells were negative to keratins 5 + 8 of the
      Moll catalogue (RCK-102), S-100 protein, lambda light-chain immunoglobulins, IgG,
      IgM, and CD3 antigen. The intratumoral T-and B-lymphocyte infiltrate was
      differentiated using CD3 antigen, lambda light-chain immunoglobulins, IgG, and
      IgM, and this technique could be useful to evaluate the regressive or progressive
      growth stage of venereal tumors. Our findings support the hypothesis of a
      histiocytic immunophenotype for CTVT, and these staining techniques could be used
      in the differential diagnosis with lymphomas.

PMID- 8740699
TI  - Histologic classification and immunophenotype of lymphosarcomas in cats with
      naturally and experimentally acquired feline immunodeficiency virus infections.
AB  - Lymphosarcoma (malignant lymphoma) is the commonest hematopoietic tumor in the
      cat. Many cases are associated with feline leukemia virus (FeLV) infection, but
      epidemiologic and experimental data suggest that feline immunodeficiency virus
      (FIV) may also have a role in lymphomagenesis. In this paper, we describe the
      clinical presentation, histologic classification, and immunophenotype of
      lymphosarcoma in eight domestic cats with natural or experimental FIV infections.
      The tumors were often of unusual distribution, with the majority of cases
      conforming to the least common anatomic classification of "miscellaneous."
      Histopathologic and immunophenotypic analysis using a panel of anti-cat and cross
      reactive anti-human monoclonal and polyclonal antibodies identified seven of
      these tumors as high-grade B cell lymphomas of the centroblastic or immunoblastic
      subtypes. The remaining case was a T-cell tumor associated with a concurrent FeLV
      infection. Our findings, together with the results of an analysis of FIV proviral
      DNA in these tumors, indicate that the B-cell lymphosarcomas were comparable to
      those observed in human and simian immunodeficiency virus infections and that the
      role of FIV in lymphomagenesis is indirect and related to the potential for
      malignant transformation during polyclonal B cell activation.

PMID- 8740700
TI  - Alimentary and respiratory tract lesions in eight medically fragile Holstein
      cattle with bovine leukocyte adhesion deficiency (BLAD).
AB  - Lesions in the alimentary tract were studied in eight medically fragile Holstein
      cattle homozygous for the bovine leukocyte adhesion deficiency (BLAD) allele as
      determined by polymerase chain reaction and restriction endonuclease analysis.
      These cattle received institutional medical care but died or were euthanatized
      because of chronic debilitation associated with diarrhea (6/8) and pneumonia
      (4/8). The six cattle with diarrhea had acute (n = 3) or chronic (n = 3)
      intestinal ulcers, but the other two remained relatively healthy for 3 years and
      did not develop intestinal tract ulcers. Ulcerated areas were present in the
      small intestine in six animals, and two of these also had ulcers in the large
      intestine. Ulcers were covered by thick exudates that, in chronic lesions,
      partially occluded the intestinal lumen. Intramural and serosal fibrosis also
      contributed to lumen constriction. Pseudomonas aeruginosa was isolated from the
      intestine of four cattle. Bovine viral disease virus and Salmonella were not
      isolated from the five cattle that were tested. Respiratory tract lesions
      consisted of dense infiltrates of neutrophils in bronchi, bronchioles, and
      alveoli. This study suggests that intestinal lesions are integral to the demise
      of BLAD cattle that receive intensive medical care and that neutrophils do
      infiltrate the lung and enter airway lumina, despite the adhesion deficiency.

PMID- 8740701
TI  - Morphometric and histopathologic analysis of lymphoid depletion in murine spleens
      following infection with Brucella abortus strains 2308 or RB51 or an htrA
      deletion mutant.
AB  - BALB/C mice were inoculated intraperitoneally with suspensions of Brucella
      abortus strains 2308 or RB51 or an htrA mutant. Spleens were examined on
      postinoculation day (PID) 2, 4, 7, 10, 15, 21, 30, and 60. Brucellae were
      cultured in high numbers from the spleens of mice infected with strains 2308 or
      htrA through PID 60; however, mice infected with strain RB51 cleared the
      infection between PID 30 and PID 60. Histopathologic changes in spleens from 2308
      infected mice were characterized by marked accumulations of macrophages, which
      expanded marginal zones beginning as early as PID 7 and persisting through PID
      60. Morphometric analysis showed a decrease in splenic white pulp in 2308
      infected mice at PID 10, which correlated with the peak of bacterial infection.
      Although this decrease was significant (P < 0.05) when compared with values at
      the previous (PID 7) and the following (PID 15) time periods, it was not
      significantly different from white pulp values noted at PID 2 or PID 4 or the
      values for control spleens. Spleens from RB51-infected mice showed only mild to
      moderate accumulations of macrophages in marginal zone areas during the peak of
      RB51 infection (PID 7-10). Morphometric analysis of RB51-infected spleens showed
      a decrease in white pulp area, which coincided with peak bacterial numbers.
      However, this decrease was not significant (P > 0.05). Spleens from mice infected
      with the htrA mutant showed moderate to marked accumulations of macrophages in
      marginal zone areas, which persisted through PID 60. Multifocal necrosis in
      lymphoid follicles as early as PID 4 was seen in both htrA and 2308 infection.
      Morphometric analysis of htrA-infected spleens revealed no significant decrease
      in white pulp and no obvious correlation with bacterial numbers in the spleen.
      These results suggest that virulent B. abortus does not induce lymphoid depletion
      significantly below those values seen in noninfected mice; thus, the possible
      role of lymphoid depletion in the pathogenesis of brucellosis remains
      questionable.

PMID- 8740702
TI  - Lesions of neonatally induced toxoplasmosis in cats.
AB  - Five pregnant queens were inoculated orally with Toxoplasma gondii tissue cysts.
      Twenty-two live and three dead kittens were born 16 to 31 days after inoculation.
      Four kittens were eaten by queens and, thus, were not available for histologic
      examination. Twenty-one kittens that died or were euthanatized on day 2 (two
      kittens), 4 (one kitten), 5 (five kittens), 6 (five kittens), 7 (one kitten), 8
      (four kittens), 16 (two kittens), and 29 (one kitten) after birth were studied
      histologically. T gondii was detected by bioassay and was seen in histologic
      sections of tissues from all 21 kittens. The histologic lesions associated with
      neonatal toxoplasmosis were widely disseminated infiltrates of macrophages and
      neutrophils often accompanied by necrosis; lymphocytes and plasma cells were
      occasionally present. The most consistent lesions were proliferative interstitial
      pneumonia (21/21); necrotizing hepatitis (20/21); myocarditis (21/21); skeletal
      myositis (21/21); glossal myositis (19/19); nonsuppurative encephalitis affecting
      the cerebrum (18/18), brain stem (15/15), and spinal cord (9/9); uveitis (19/19);
      necrotizing adrenal adenitis (18/18); and interstitial nephritis (16/21).
      Placental lesions (2/2) consisted of grossly visible areas of necrosis and
      mineralization.

PMID- 8740703
TI  - Lesions of acute inhaled lethal ricin intoxication in rhesus monkeys.
AB  - Five unimmunized adult rhesus monkeys weighing 5.9-6.3 kg were challenged with a
      precalculated, inhaled dose of 20.95-41.8 micrograms/kg of aerosolized ricin. Two
      males and three females either died or were killed at the onset of respiratory
      distress between 36 and 48 hours post-ricin inhalation and were necropsied.
      Consistent gross and microscopic lesions were confined to the thoracic cavity.
      All monkeys had multifocal to coalescing fibrinopurulent pneumonia, diffuse
      necrosis, and acute inflammation of airways, and nearly diffuse alveolar
      flooding, with peribronchovascular edema. All monkeys also had purulent
      tracheitis, fibrinopurulent pleuritis, and purulent mediastinal lymphadenitis.
      One male monkey and one female monkey had bilateral adrenocortical necrosis. We
      attributed the cause of death to asphyxiation following massive pulmonary
      alveolar flooding. The lesions of acute inhaled ricin intoxication in rhesus
      monkeys closely resembled those lesions reported in rats with acute inhaled ricin
      intoxication.

PMID- 8740704
TI  - Immunohistochemical detection of lymphocyte subpopulations in the tarsal joints
      of chickens with experimental viral arthritis.
AB  - We characterized the lymphocytes in the tarsal joint synovium of chickens
      inoculated with an arthrotropic strain of avian reovirus. Cryostat sections of
      whole joints taken from 2 days to 35 days postinoculation were analyzed using
      monoclonal antibodies directed against B lymphocytes, T lymphocytes, and chicken
      Ia antigen. Plasma cells were morphologically identified using stained sections
      of whole joints. Time-dependent changes were found in the type and number of
      positively staining cells. Synoviocytes and cells with a dendritic morphology
      stained positive for Ia in normal joint sections. T cells, mostly CD8 positive,
      were present in low numbers in acute phase arthritis (2-6 days postinfection) in
      the perivascular and superficial regions of the synovium. Subacute arthritis (8
      14 days postinfection) was characterized by increased numbers of CD4 and Cd8 T
      cells in the perivascular and superficial regions. The perivascular T cells began
      to organize into aggregates, with IgM-positive B cells and plasma cells on the
      periphery of these aggregates. Some CD8-positive cells were detected on the
      surface of the articular cartilage. Cells staining positively for Ia were not
      lymphocytes. Chronic arthritis ( > 14 days postinfection) was characterized by
      large numbers of T cells in the perivascular and superficial regions, with the
      CD4-positive T cells found primarily in the lymphoid aggregates of the
      perivascular regions. IgM-positive B cells were fewer, but more plasma cells, few
      of which stained positive for IgM, were present. Lymphocytes in chronic arthritis
      stained positively for Ia. These data suggest that the types, numbers, and
      activation level of lymphocytes present in the tarsal joints are similar but not
      identical to those seen in rheumatoid arthritis.

PMID- 8740705
TI  - Distribution of virus and viral antigen in specific pathogen-free calves
      following inoculation with noncytopathic bovine viral diarrhea virus.
AB  - Gross and microscopic lesions and distribution of virus were studied in specific
      pathogen-free calves (SPF) 10 days post-inoculation (PI) with bovine viral
      diarrhea virus (BVDV). To investigate possible differences in tissue tropism
      between BCDV isolates, two clinically and antigenically different noncytopathic
      (ncp) isolates of BVDV were compared in the study. Four calves were exposed to
      noncytopathic (ncp) BVDV 7937, and four to ncp-BVDV 126. Two additional calves
      that were not exposed to virus served as controls. Both ncp-BVDV 7937 and ncp
      BVDV 126 induced mild disease characterized by variable fever and anorexia.
      Lymphoid depletion was evident in Peyer's patch of four calves and the thymus of
      two calves exposed to BVDV. Differences between these isolates in the
      distribution of BVDV or BVDV antigen in tissues of inoculated calves were not
      found. High concentrations of BVDV and BVDV-specific antigen were detected in the
      thymus, Peyer's patch, and mesenteric lymph node of all exposed calves. BVDV was
      shown to infect cells of the bone marrow without causing microscopic lesions.
      High concentrations of BVDV were recovered from the bone marrow of all calves
      exposed to BVDV and BVDV-specific antigen was demonstrated at this location in
      six of these calves. Platelet counts of calves exposed to BVDV were significantly
      reduced during infection, which resulted in thrombocytopenia in one calf. Focal
      areas of necrosis were observed in squamous epithelial cells of the tonsil and
      ruminal mucosa. BVDV-specific antigen was found in and adjacent to these foci.
      Calves exposed to ncp-BVDV 7937 had slightly more severe clinical signs than
      those exposed to ncp-BVDV 126.

PMID- 8740706
TI  - Comparative effects of bluetongue virus infection of ovine and bovine endothelial
      cells.
AB  - Bluetongue virus (BTV) infection results in disparate clinical syndromes among
      ruminant species. An in vitro model system of BTV/target cell interaction was
      developed using umbilical vein endothelial cells (EC)from fetal lambs and calves.
      These cells had microscopic, ultrastructural, and immunocytochemical features
      typical of EC. BTV infection in these cells was examined using virus binding
      assays, plaque assays, a whole-cell enzyme-linked immunosorbent assay, flow
      cytometry, electron microscopy, and a bioassay for interferon activity. EC from
      both species supported cytopathic BTV infections. Ovine EC bound more BTV
      initially and produced more virus over time, whereas bovine EC underwent more
      rapid lysis subsequent to infection. An ultrastructural comparison of BTV
      infected ovine and bovine EC, grown as differentiated capillary-like cords on a
      laminin-rich matrix or as monolayers, revealed no significant interspecies
      differences in viral morphogenesis between 1 minute and 24 hours after infection.
      The intracellular distribution of BTV nonstructural protein 1, which localized to
      virus inclusion bodies and tubules, was identical for ovine and bovine
      endothelial cells. Ovine and bovine EC produced a soluble mediator of interferon
      activity in response to BTV infection; however, ovine EC produced higher levels
      of interferon activity at lower levels of infection. These findings indicate
      differences in BTV-EC interaction that may contribute to the pathogenesis of the
      severe inflammatory disease that is characteristic of clinical bluetongue disease
      in sheep.

PMID- 8740707
TI  - Effect of substrate on indirect immunofluorescence test for canine pemphigus
      foliaceus.
AB  - The effect of substrate on indirect immunofluorescence (IIF) tests for the
      detection of circulating autoantibodies was studied by examining sera from 14
      canine pemphigus foliaceus patients, six sera with non-pemphigus dermatoses and
      ten normal dog sera against five different substrates from three species. These
      substrates included bovine esophagus, bovine nose, bovine tongue, monkey
      esophagus, and canine nose skin. Nine out of 14 (64.3%) sera from patients with
      canine pemphigus foliaceus showed intercellular space staining by indirect
      immunofluorescence using bovine esophagus as substrate. However, sera from
      nonpemphigus dermatoses and normal dog did not react with bovine esophagus. In
      other substrates, only bovine tongue showed 1/8 (12.5%) positive reaction at the
      intercellular space by sera from canine pemphigus foliaceus. Dog nose skin showed
      the intercellular space staining against ten of ten (100%) normal dog serum.
      Monkey esophagus showed the fluorescent deposit at the intercellular space in
      four of nine (44.4%) of pemphigus foliacues dog sera, however, four of ten (40%)
      of normal dog sera revealed nonspecificity intercellular staining. These results
      indicate that the sensitivity and the specifity of IIF test in canine pemphigus
      foliaceus depend on the substrate. The best substrate for detecting circulating
      autoantibody in canine pemphigus foliaceus patients among five different
      substrates was bovine esophagus because of its sensitivity and high specificity.
      The diagnosis of canine pemphigus foliaceus should be made on the basis of a
      combination of clinical signs, histopathology, direct immunofluorescence, and the
      detection of circulating autoantibody.

PMID- 8740708
TI  - Distribution of bluetongue virus in tissues of experimentally infected pregnant
      dogs as determined by in situ hybridization.
AB  - Six female dogs (four pregnant and two nonpregnant) were inoculated with
      bluetongue virus (BTV), serotype 11. Pregnant animals and one nonpregnant dog
      received 5.5-6.3 log10 of cell culture-adapted virus. The other nonpregnant dog
      received a modified live vaccine contaminated with bluetongue virus. The non
      pregnant animals never became clinically ill and were euthanatized 35 days post
      inoculation. Three of the four pregnant dogs aborted, and all four died or were
      euthanatized 5-10 days post-inoculation. The predominant pathologic feature in
      the adults was severe pulmonary edema. Various tissues from the bitches and
      fetuses were examined by in situ hybridization using a digoxigenin-labeled probe
      corresponding to the nonstructural protein-1 gene of BTV-17. By this technique,
      viral nucleic acid was detected predominantly in endothelial cells of lung of all
      four dogs, with lesser amounts in capillaries of uterus, spleen, and kidney in
      some of the dogs. In two adult dogs, bluetongue viral nucleic acid was detected
      in mononuclear cells of the periarteriolar lymphoid sheaths of spleen. There was
      minimal staining of capillaries in placenta in three of the five fetuses
      examined. There was no viral nucleic acid detected in any of the other fetal
      tissues.

PMID- 8740709
TI  - Immunohistochemical detection of virulence-associated antigens of Rhodococcus
      equi in pulmonary lesions of foals.
AB  - Rhodococcus equi was isolated from the lungs of six foals with bronchopneumonia.
      All isolates expressed 15-17-kd antigens by immunoblot analysis and contained a
      virulence-associated plasmid of 85 or 90 kb. Immunohistochemically, R. equi from
      all pulmonary lesions showed the expression of 15-17-kd antigens mainly in the
      phagocytic cells. The specific monoclonal antibody to 15-17-kd antigens of R.
      equi (MAb 10G5) may be an aid in the diagnosis of R. equi-induced pneumonia.

PMID- 8740710
TI  - Coinfection of a bearded dragon, Pogona vitticeps, with adenovirus- and
      dependovirus-like viruses.
AB  - Four neonate bearded dragons, Pogona vitticeps, from two collections became ill
      and died. Multiple tissues were collected and processed for light microscopy. In
      hematoxylin and eosin-stained sections of liver of one lizard, numerous
      basophilic intranuclear inclusions were observed. In three lizards, intranuclear
      inclusions were primarily seen within enterocytes in the small intestine. A
      portion of paraffin-embedded liver of one lizard and small intestine of a second
      lizard were removed, deparaffinized, and examined by electron microscopy. For the
      most part, inclusions in the liver consisted of nonenveloped viral particles 60
      66 nm in diameter. Smaller nonenveloped virions 15-17 nm in diameter were
      occasionally seen in association with these particles. In the intestine,
      inclusions consisted only of 60-70 nm particles. Based on morphology and
      location, the larger particles were consistent with an adenovirus. Based on size
      and presence within nuclei of host cells coinfected with the adenovirus-like
      virus, the smaller viral agent was consistent with members of the genus
      Dependovirus.

PMID- 8740711
TI  - Conjunctival mycobacteriosis in two emus (Dromaius novaehollandiae).
AB  - Avian tuberculosis was diagnosed in two young adult female commercial emus
      (Dromaius novaehollandiae) with granulomatous conjunctivitis. Histologically, the
      granulomas appeared typical of avian tuberculosis. Caseonecrotic cores were
      surrounded by a broad ring of palisading epithelioid macrophages and
      multinucleate giant cells with a moderate admixture of heterophils, lymphocytes,
      and plasma cells. One conjunctival granuloma had multifocal mineralization. At
      necropsy, granulomas were also found in visceral organs of both birds. Acid-fast
      bacilli were demonstrated in all lesions using Ziehl-Neelsen or Fite's stains.
      Culture confirmed the bacilli to be Mycobacterium avium (complex).

PMID- 8740712
TI  - Primary epitheliotropic alimentary T-cell lymphoma with hepatic involvement in a
      dog.
AB  - The anatomic forms of lymphoma are multicentric, alimentary, thymic, cutaneous,
      and leukemic. Correlations between cell type and topographic distribution of
      lymphomas is not well documented, but there are more plasmacytoid tumors in the
      gut, skin, and spleen, which suggests that these are areas of malignant
      transformation preceded by a period of benign immune hyperplasia. Alimentary
      forms of lymphoma can be preceded by lymphocytic-plasmacytic enteritis. In the
      present case, an epitheliotropic alimentary form of T-cell lymphoma with hepatic
      involvement and concomitant lymphocytic-plasmacytic enteritis was diagnosed in an
      8-year-old male Labrador Retriever. The lymphoma was characterized by the
      accumulation of atypical lymphocytes in the lamina propria and mucosal epithelium
      of the jejunum. The lymphocytes were identified as T-cell lineage using a
      polyclonal rabbit antisera to the human pan-T-cell determinant CD-3. The "homing"
      nature of the neoplasm resembles the epidermotropic form of cutaneous T-cell
      lymphoma.

PMID- 8740713
TI  - Lymphangiosarcoma in a young dog.
AB  - Lymphangiosarcoma was diagnosed from biopsy material obtained from an 8-week-old
      puppy with a progressively enlarging subcutaneous inguinal swelling.
      Histologically, the tumor was composed of endothelial cells immediately adjacent
      to large collagen bundles. Tumor cells formed irregular vascular channels which
      extended along the connective tissue investments of small vessels and nerves of
      the subcutis and deep dermis. Similar neoplastic tissue extensively infiltrated
      an inguinal lymph node. Neoplastic cells were immunohistochemically stained for
      factor 8-related antigen and were weakly positive when compared with several
      hemangiomas and hemangiosarcomas. Transmission electron microscopy revealed
      numerous micropinocytotic vesicles and a continuous basal lamina. The puppy was
      euthanatized at 8 months of age due to severe septic polyarthritis.
      Lymphangiosarcoma was documented at the site of the original tumor as well as in
      the axillary lymph node at necropsy.

PMID- 8740714
TI  - Ubiquitin expression in degenerating axons of equine cervical compressive
      myelopathy.
AB  - Neuropathologic examination revealed axonal swelling and breakdown leading to
      Wallerian degeneration of affected myelinated nerve fibers in the spinal cord
      white matter of four young horses with equine cervical compressive myelopathy.
      Immunohistochemical reactions for the cell stress protein ubiquitin revealed an
      enhanced presence in the swollen axons, which may reflect a role for ubiquitin in
      the neuronal catabolic process of axonal compression and degeneration in this
      myelopathy.

PMID- 8740715
TI  - Intestinal spirochetosis and giardiasis in a beagle pup with diarrhea.
AB  - This report describes the light microscopic and ultrastructural changes in a 3
      month-old dog with naturally acquired intestinal spirochetosis and giardiasis. It
      was concluded that the pathogenetic characteristics of weakly beta-hemolytic
      spirochetes associated with colitis in this pup were similar to those associated
      with human and porcine spirochetal diarrhea.

PMID- 8740716
TI  - Metastatic multicentric neurofibrosarcoma of the lumbosacral plexus in a cow.
AB  - A metastatic multicentric neurofibrosarcoma of the lumbosacral plexus in an adult
      cow is described. The left lumbosacral plexus was obliterated by a mass which
      extended through the intervertebral foramen into the spinal canal and between the
      dorsal arches of the fifth and sixth lumbar vertebrae. A closely associated
      (possibly contiguous) mass extended into and separated the left sacroiliac joint.
      Multiple similar masses involved peripheral nerves and skeletal muscles of the
      pelvis, pelvic limbs, and abdominal wall. Metastatic lesions were scattered
      throughout the lungs. The lumbosacral lesion and all other masses consisted of
      interwoven bundles of loosely cohesive, elongated cells separated by variable
      collagenous matrix. Many neoplastic cells were positive for S-100 protein.
      Ultrastructurally, fibroblastic cells were mixed with scattered cells possessing
      schwannian characteristics.

PMID- 8740717
TI  - Lysosomal storage disease in an emu (Dromaius novaehollandiae).
AB  - Lysosomal storage disease involving the brain, spinal cord, liver, and spleen was
      discovered in a 6-month-old male emu (Dromaius novaehollandiae). The diagnosis
      was based on light and electron microscopic studies and histochemical staining
      characteristics. This is the first case of lysosomal storage disease reported in
      a ratite.

PMID- 8740718
TI  - Chemotherapy of gastric cancer.
AB  - Patients with gastric adenocarcinomas have a poor prognosis. Because curative
      surgery is often impossible (metastatic disease) or extremely difficult (locally
      advanced tumors), and the majority of patients undergoing curative resection
      relapse, chemotherapy has been actively studied in gastric cancer. Many drugs
      have shown activity; however, single-agent chemotherapy failed to demonstrate
      increased survival benefit. Several combination regimens have been developed with
      high activity in locally advanced and metastatic disease. Among them are 5
      fluorouracil (5-FU) plus high dose methotrexate plus doxorubicin (FAMTX),
      etoposide plus doxorubicin plus cisplatin (EAP), etoposide plus leucovorin plus 5
      FU (ELF), and epirubicin plus cisplatin plus 5-FU (ECF). Although the response
      rates of these schedules are encouraging, the toxicity is considerable.
      Randomized trials comparing chemotherapy with best supportive care showed an
      increase in overall survival and in quality-of-life. Up to now adjuvant
      chemotherapy in curatively resected gastric cancer patients has failed to improve
      survival as compared with surgical controls. Phase II trials with preoperative
      chemotherapy have shown very promising results, but results of randomized trials
      should be awaited to judge the real value of this approach. At this moment it
      cannot yet be estimated whether preoperative chemotherapy does positively
      influence the resection rate and survival of patients with clinically resectable
      tumors.

PMID- 8740719
TI  - Interferon and hormone sensitivity of endocrine-related tumors.
AB  - Interferons (IFNs) have been shown to enhance both in vitro and in vivo the
      antiproliferative activity of some hormones and anti-hormones which mainly act
      via steroid receptors. We discuss some of the mechanisms which could be involved
      in determining this effect in breast, endometrial and prostatic cancer cells,
      with a particular emphasis on steroid receptor modulation, reduction of the
      expression of epidermal growth factor receptors and, finally, down-regulation of
      some oncogenes. It seems that under appropriate conditions IFN might produce
      changes in cancer cells that enhance or restore hormone sensitivity.
      Nevertheless, available clinical data are too few to allow any conclusion to be
      drawn and this problem merits further investigations.

PMID- 8740720
TI  - Taxol and vinorelbine: a new active combination for disseminated malignant
      melanoma.
AB  - We evaluated the activity and toxicity of two sequences of taxol combined with
      vinorelbine in disseminated malignant melanoma, metastatic beyond regional lymph
      nodes. Fifteen previously untreated patients, nine males and six females (median
      age 56 years), were enlisted between May 1994 and February 1995. Eight patients
      received vinorelbine 30 mg/m2 (maximum dose 50 mg) first, follow 24 h later by
      taxol 120 mg/m2 (maximum dose 240 mg) infused over 3 h (the V/T sequence). Seven
      patients received the reverse (T/V) sequence. In 79 administered courses there
      were no anaphylactic episodes, the main toxicity being alopecia (WHO grade 3).
      Significant neutropenia, emesis or neuropathy was not observed in either schedule
      (WHO grades 0 or 1). Three major responses, all with the V/T sequences, were
      seen; one complete (CR) in nodal and cutaneous sites lasting 13 months and two
      partial (PR), omental, ascites in one and hepatic, splenic and nodal in the
      other, lasting 7 and 6 months, respectively. Clinically meaningful tumor
      regressions, not qualifying strictly for the criteria of major response, were
      observed in two additional patients in the T/V sequence. Taxol combined with
      vinorelbine is active against disseminated malignant melanoma. The importance of
      sequencing the two drugs remains to be determined with accrual of more patients
      into the study.

PMID- 8740721
TI  - Phase I and pharmacology study of intoplicine (RP 60475; NSC 645008), novel
      topoisomerase I and II inhibitor, in cancer patients.
AB  - Intoplicine (RP 60475F; NSC 645008) is a novel 7H-benzo[e]pyrido[4,3-b]indole
      derivative which interacts with both topoisomerases I and II. Because of its high
      activity in preclinical cancer models, original mechanism of action and
      acceptable toxicity profile, intoplicine was further evaluated in a phase I and
      pharmacology study. Thirty-three (33) patients (24 men and nine women) meeting
      standard phase I eligibility criteria were included: median age was 56 years,
      performance status 0-1 in 28 patients and 2 in five patients. Tumor primary sites
      were head and neck (9), colon (6), lung (3) and various other sites (15). Thirty
      one patients had received prior radiotherapy and/or chemotherapy. Sixty-nine
      coursed of intoplicine were administered as a 1 h i.v. infusion at dose levels
      ranging from 12 to 360 mg/m2. Dose-dependent and reproducible hepatotoxicity was
      dose limiting in three out of four patients at 360 mg/m2: this toxicity was
      reversible in two of three patients, but fatal in one. Two sudden deaths occurred
      in this study at 12 and 48 mg/m2, and the drug implication could not be excluded.
      No myelosuppression was noted. Hepatotoxicity is therefore dose limiting at 360
      mg/m2, and the phase II recommended dose is 270 mg/m2 every 3 weeks with close
      monitoring of hepatic and cardiac functions. Intoplicine pharmacokinetics was
      determined in plasma (23 patients) and whole blood (18 patients) at doses ranging
      from 12 to 360 mg/m2. Intoplicine plasma concentration decay was either bi- or
      triphasic with the following pharmacokinetic values (mean +/- SEM): half-life
      alpha, 0.04 +/- 0.004 h; half-life beta, 0.61 +/- 0.13 h; terminal half-life,
      19.4 +/- 4.0 h; mean residence-time (MRT), 11.3 +/- 2.4; total plasma clearance
      (CL), 74 +/- 5 l/h; volume of distribution beta (V beta), 1982 +/- 477 l: volume
      of distribution at steady state (Vss): 802 +/- 188 l. both the area under the
      plasma concentration versus time curves (AUC) and the maximum plasma
      concentrations (Cmax) increased linearly with the intoplicine dose, indicating
      linear pharmacokinetics (AUC: r = 0.937; slope = 0.01305; p < 0.001; Cmax: r =
      0.847; slop = 0.01115; p < 0.001). Plasma AUC was also predicted very accurately
      by the Cmax values (r = 0.909; slope = 1.0701; p < 0.001). Other plasma
      pharmacokinetic parameter values increased significantly with dose, e.g. the
      terminal half-life (r = 0.748, p < 0.001) the MRT (r = 0.728, p < 0.001), the V
      beta (r = 0.809, p < 0.001), and the Vss (r = 0.804, p < 0.001). This was
      probably due to a longer detectability of the drug in plasma at higher doses.
      Blood pharmacokinetics was also evaluated in 18 patients since it was found that
      red blood cells represented a significant drug reservoir for intoplicine. Blood
      intoplicine disposition curves were either bi- or triphasic with the following
      pharmacokinetic parameter values (mean +/- SEM): half-life alpha, 0.04 +/- 0.01
      h; half-life beta, 0.94 +/- 0.22 h; terminal half-life, 57.1 +/- 6.6 h; MRT, 82.2
      +/- 9.9 h; CL, 18 +/- 3 l/h; V beta, 1188 +/- 147 I; Vss 1163 +/- 138 I. Blood
      pharmacokinetics was linear, since AUC and Cmax increased linearly with dose
      (AUC: r = 0.879; slop = 0.06884; p < 0.001; Cmax: r = 0.835, slop = 0.01223; p <
      0.001). Blood AUC values could also be determined by the blood Cmax (r = 0.768;
      slop = 5.0206; p < 0.001). Other blood pharmacokinetic parameter values presented
      a dose dependence, e.g. the terminal half-life (r = 0.626, p = 0.005), the V beta
      (r = 0.682, p = 0.002) and the Vss (r = 0.555, p = 0.017). The plasma or blood
      intoplicine concentrations achieved in vivo in humans are potentially cytotoxic
      levels based on preclinical in vivo and in vitro data. In conclusion, the phase
      II recommended dose of intoplicine is 270 mg/m2 administered as a 1 h i.v.
      infusion every 3 weeks. Plasma and blood pharmacokinetics were linear within the
      dose range studied. Potentially cytotoxic concentrations were reached at
      clinically achievable doses.

PMID- 8740722
TI  - Long-term results of continuous treatment with recombinant interferon-alpha in
      patients with metastatic carcinoid tumors--an antiangiogenic effect?
AB  - This study investigated the efficacy of long-term continuous and dose-escalated
      interferon-alpha (IFN) treatment in patients with progressive carcinoid tumors.
      In this single-institution, phase II study 16 chemotherapy-naive, eligible
      patients were entered. Interferon treatment consisted on 5 MIU IFN three times
      weekly s.c. until radiologic progression. In case of progression the dose was
      increased to 10 MIU. Radiologic and biochemical evaluation was done monthly and
      thereafter 3 monthly. We have treated 16 patients of whom 15 are evaluable for
      tumor response. Calculated by standard response criteria, three patients
      experienced a partial response. Another three had an important minor response.
      Median response duration was 24 months (range 18-51 months). Biochemical
      responses were observed in nine out of 12 patients with an elevated 5
      hydroxyindoleacetic acid excretion. The serum neuron-specific enolase proved a
      reliable marker for both response and progression. In the one patient progressive
      after 3 months, a dose increment to 10 MIU was without effect. In patients
      initially not progressing or responding to 5 MIU, escalation to 10 MIU had a
      short lasting beneficial effect in three cases. The radiological characteristics
      and the kinetics of these responses are compatible with an anti-angiogenic effect
      of IFN. This study of IFN in carcinoid tumors confirms the activity in this
      disease. Our results demonstrate the necessity of initiating treatment only in
      radiologically progressive patients and continuing this treatment until
      progression. We feel that currently the activity of IFN in metastatic carcinoid
      tumors compares favorably with that of systemic chemotherapy in patients with
      progressive disease.

PMID- 8740723
TI  - Paclitaxel sensitizes multidrug resistant cells to radiation.
AB  - The unique action of paclitaxel, to stabilize microtubules and block cells at the
      radiosensitive G2M phase of the cell cycle, suggests, it may sensitize tumors to
      radiotherapy. We have investigated the potential of this interaction to overcome
      multidrug resistance in vitro using the HL60 cell line and its P-glycoprotein
      expressing, multidrug resistant H/E8 subline. HL60 cells showed a modest 1.4-fold
      (p < 0.01) increase in sensitivity to 2 Gy radiation given 24 h after a 1 h
      treatment with paclitaxel. The H/E8 subline, which has increased radiation
      resistance and expresses an extended multidrug resistance phenotype, showed
      significant sensitization to radiation (up to 2.3-fold sensitization; p < 0.01)
      even with doses of paclitaxel which had no effect on cell viability or were
      associated with any G2/M block in the cell cycle. In the presence of verapamil,
      an inhibitor of P-glycoprotein mediated efflux, drug resistant cells could be
      sensitized to 2 Gy radiation by similar paclitaxel doses as the parental cell (>
      or = 30 nM; p < 0.01). These results indicate a therapeutic advantage may be
      possible in the treatment of resistant tumors by the combined use of paclitaxel
      with radiation.

PMID- 8740724
TI  - Terminally L-modified oligonucleotides: pairing, stability and biological
      properties.
AB  - An oligodeoxynucleotide (ODN), capable of reducing the growth of human B
      lymphocytes carrying the t(14;18) chromosome translocation, was prepared in
      different 'chemical versions': unmodified phosphodiester, phosphorothioate and
      phosphodiester capped with L-2'-deoxycytidine. Their binding affinity to the
      complementary synthetic target was studied by the melting point assay. The ODNs,
      administered to DOHH2 cells, were compared for stability in the culture medium,
      cellular uptake, time course of the intact sequence concentration within the cell
      and ability to inhibit cell growth. The 5', 3'-L-capped derivative and the
      phosphorothioate had comparable potency, superior to that of the unmodified ODN,
      in agreement with the concentration of undegraded ODNs within the cell.

PMID- 8740725
TI  - Effects of lycopene, a carotenoid, on intrathymic T cell differentiation and
      peripheral CD4/CD8 ratio in a high mammary tumor strain of SHN retired mice.
AB  - We previously reported that lycopene, one of the carotenoids, significantly
      suppressed the development of spontaneous mammary tumors of mice and the
      contribution of lycopene to the maintenance of physical homeostasis was
      suggested. In this study, we investigated the effects of lycopene on the
      intrathymic and peripheral T cell subpopulation as immunoregulatory parameters.
      In tumorous control mice, inactivation of intrathymic T cell differentiation, an
      increase of the percentage of CD4+ CD8+ cells and a decrease of CD4+CD8+ cells
      were observed. On the other hand, in the lycopene-treated mice, the abnormal
      intrathymic T cell differentiation was recovered and brought to non-tumorous
      levels. The peripheral CD4/CD8 ratio was partially augmented by lycopene
      treatment which resulted from an increased CD4+ subpopulation. These observations
      suggest that one of the immunomodulating roles of lycopene is to normalize the
      change of intrathymic T cell differentiation caused by tumorigenesis.

PMID- 8740726
TI  - 1-(2-Tetrahydrofuryl)-5-fluorouracil in combination with uracil suppresses
      mammary carcinogenesis and growth of tumors induced with 7,12
      dimethylbenz[a]anthracene in rats.
AB  - The effects of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil
      (UFT) on mammary carcinogenesis and growth of tumors induced with 7,12
      dimethylbenz[a]anthracene (DMBA) were investigated in rats. Daily oral
      administration of UFT reduced the incidence and number of mammary tumors compared
      with those of the DMBA control group, resulting in lower activities in DNA
      synthesizing enzymes, thymidylate synthetase and thymidine kinase, and a
      reduction of bromodeoxyuridine-immunoreactive (S-phase) cells in mammary tumors
      of UFT-treated rats.

PMID- 8740727
TI  - In vivo/in vitro studies on the effects of cyclophosphamide on growth and
      differentiation of hamster palate.
AB  - A study was undertaken to examine the effects of cyclophosphamide (CP) on growth
      and differentiation of palatal tissues. An in vivo/in vitro approach was designed
      to analyze (1) whether the damage caused by in vivo administration of CP in the
      developing palate can be altered in vitro, and (2) to determine the effects of CP
      on the synthesis of collagen and glycosaminoglycan (GAG), which are essential for
      proper palate development. In addition, effects of vitamin B1 and/or B6 on in
      vivo modulation of CP teratogenicity was evaluated. Pregnant hamsters were given
      30 mg/kg CP or 1 ml saline on day 10 of gestation. Control and CP-treated
      embryonic palates were dissected on day 11 of gestation and incubated in vitro in
      the presence or absence of CP. In order to allow metabolic activation of CP in
      vitro, either a slice of hamster liver or microsomal S9 fraction of liver was
      added to the culture medium. To study collagen and GAG synthesis, palates were
      obtained between days 10 and 13 of gestation, and incubated in growth medium
      supplemented with [14C]proline or [3H]glucosamine, as appropriate. The rates of
      collagen and GAG synthesis were determined. The results showed that, in the
      controls, the presence of a liver slice or S9 fraction in the culture medium had
      no effects on in vitro closure of palate. In vivo CP exposed palates did not fuse
      in vitro. When drug was given in vitro, or both in vivo and in vitro, palatal
      closure did not occur. CP reduced synthesis of both collagen and GAG in the
      vertically developing palate. The drug-treated shelves reoriented only after the
      rates of collagen and GAG synthesis were restored to the levels comparable to the
      control counterparts. Co-administration of vitamin B1 and B6 did not interfere
      with the teratogenicity of CP. It was suggested that CP treatment affected DNA
      synthesis and injured growing cells, which in turn reduced the synthesis of GAG
      and collagen and affected the expansion of shelf volume to delay the
      reorientation of the palatal shelves. Furthermore, it appears that in vivo
      treatment with CP changes the programming of palatal tissues to prevent the
      fusion process in vivo, which could not be altered in vitro.

PMID- 8740728
TI  - Modification of the blood-brain barrier permeability by vinorelbine: effect of
      intracarotid infusion compared with intravenous infusion.
AB  - Brain levels of the antineoplastic compound, vinorelbine, and its effects on the
      permeability of the blood-brain barrier (BBB) were studied. Preliminary
      experiments were carried out to define the dose of 10 mg/kg and the delay of 3 h
      after infusion required to induce BBB disruption. Vinorelbine was infused by i.c.
      or i.v. infusion to anesthetized male Sprague-Dawley rats. BBB disruption was
      evaluated qualitatively by the presence in the infused hemisphere of i.v.
      administered Evans blue dye (2%) and vinorelbine intratissular levels were
      measured by HPLC. After an i.c. infusion, there is an important variability in
      the degree of extravasation of Evans blue albumin complex, which is correlated
      with vinorelbine levels (p < 0.01). The percent of dose in brain tissue is less
      than 1%. After an i.v. infusion, the parenchyma is globally affected as shown by
      the uniform faint bluish staining of the two hemispheres. Vinorelbine levels are
      homogenous and similar to levels of brains graded + 1 after an i.c. infusion.
      These results seem to indicate that an i.c. infusion induces localized BBB
      disruptions while the effect of an i.v. infusion is global and that the gain in
      tissue level after an i.c. infusion is low compared with i.v. infusion.

PMID- 8740729
TI  - Percutaneous intratumoral injection of cisplatin microspheres in tumor-bearing
      rats to diminish acute nephrotoxicity.
AB  - Poly(D,L-lactide) microspheres loaded with cisplatin (PLA-CDDP MS) were prepared
      by a solvent evaporation technique for direct intratumoral injection. The
      microspheres, 50-100 microns, containing 40.04% of cisplatin produce sustained
      release in vitro. PLA-CDDP MS (6 mg/kg body weight of cisplatin) suspensions were
      injected intratumorally into mammary tumors in rats. Cisplatin solution (6 mg/kg
      body weight) was injected either intratumorally or intraperitoneally in two
      groups. After treatments, the tumor size decreased in each of the groups as a
      function of time. Sixteen days post-injection, the tumors had either disappeared
      or significantly shrunk. PLA-CDDP MS had a similar antitumor effect compared with
      cisplatin aqueous solution. Blood urea nitrogen, serum creatinine and
      histopathology examinations revealed that the renal toxicity in the PLA-CDDP MS
      group was significantly less than in the control groups. These results indicate
      that intratumoral injection of PLA-CDDP MS maintains anticancer potency and
      reduces acute renal toxicity.

PMID- 8740730
TI  - Intra-abdominal desmoplastic small cell tumors: report of two cases.
AB  - Two young adults that presented with intra-abdominal desmoplastic small cell
      tumors (DSCT) without any evidence of a primary site are described. Both cases
      share the clinical characteristic features of this rare tumor which include
      predominant intra-abdominal location as initial presentation, nesting pattern of
      growth, intense desmoplastic reaction, immunohistochemical reactivity for
      epithelial, neural and muscle markers, and highly aggressive behavior. Aggressive
      chemotherapy with a cisplatin-containing regimen was the main therapy to our
      patients. Up to the present, both cases are alive with disease. The survival is
      18 and 15 months from the initial diagnosis, respectively. Interestingly, one of
      the cases encountered an episode of cerebral infarction at the territory of the
      left middle cerebral artery 12 days after the first cycle of chemotherapy. This
      is a previously unrecognized manifestation for this tumor type. This causal
      relationship between chemotherapy and an acute vascular event is the most likely
      explanation for our patient's stroke.

PMID- 8740731
TI  - Melanoma incidence In Europe.

PMID- 8740732
TI  - Incidence of breast cancer in Norwegian female radio and telegraph operators.
AB  - Exposure to electromagnetic fields may cause breast cancer in women if it
      increases susceptibility to sex-hormone-related cancer by diminishing the pineal
      gland's production of melatonin. We have studied breast cancer incidence in
      female radio and telegraph operators with potential exposure to light at night,
      radio frequency (405 kHz-25 MHz), and, to some extent, extremely low frequency
      fields (50 Hz). We linked the Norwegian Telecom cohort of female radio and
      telegraph operators working at sea to the Cancer Registry of Norway to study
      incident cases of breast cancer. The cohort consisted of 2,619 women who were
      certified to work as radio and telegraph operators between 1920 and 1980. Cancer
      incidence was analyzed on the basis of the standardized incidence ratio (SIR),
      with the Norwegian female population as the comparison group. The incidence of
      all cancers was close to unity (SIR = 1.2). An excess risk was seen for breast
      cancer (SIR = 1.5). Analysis of a nested case-control study within the cohort
      showed an association between breast cancer in women aged 50+ years and shift
      work. In a model with adjustment for age, calendar year, and year of first birth,
      the rate ratio for breast cancer associated with being a radio and telegraph
      operator--in comparison with all Norwegian women born 1935 or later--analyzed
      with Poisson regression, was 1.5 after adjustment for fertility factors. These
      results support a possible association between work as a radio and telegraph
      operator and breast cancer. Future epidemiologic studies on breast cancer in
      women aged 50 and over, should address possible disturbances of chronobiological
      parameters by environmental factors.

PMID- 8740733
TI  - Decreasing rates of cervical cancer among American Indians and Hispanics in New
      Mexico (United States).
AB  - Minority women in New Mexico (United States)--including American Indian and
      Hispanic women--have shown disproportionately high incidence rates of invasive
      cervical cancer during the 1960s and 1970s. Several public health programs in New
      Mexico were directed toward early detection of cervical cellular abnormalities,
      particularly targeting the state's minority women. To evaluate the effectiveness
      of these programs, we examined the New Mexico Surveillance, Epidemiology, and End
      Results (SEER) data collected from 1969-92, and calculated average annual, age
      specific, and age-adjusted incidence rates by ethnic group (American Indian,
      Hispanic, and non-Hispanic White) for five-year time intervals. We also
      calculated age-adjusted mortality rates for cervical cancer in the same ethnic
      groups using state vital records. Age-adjusted incidence rates for invasive
      cervical cancer show substantial temporal decreases, especially for minority
      women in the state. The age-adjusted incidence rate decreased by 66 percent, from
      30.3 to 10.3 per 100,000 for American Indian women, and by 61 percent, from 26.1
      to 10.2 per 100,000 for Hispanic women. A stage shift to earlier stages of
      cervical neoplasia occurred over the study period, with a substantially higher
      proportion of in situ compared with invasive cancers diagnosed in the most recent
      cf the most remote time period. The ratio of incidence rates of in situ to
      invasive cancers changed dramatically for both American Indian and Hispanic
      women. Cervical cancer mortality rates decreased steadily among Hispanic women
      from 1958 to 1992; the decrease among American Indian women was less stable and
      fluctuated due to small numbers. Ongoing targeted screening programs should help
      to reduce cervical cancer incidence and mortality further in New Mexico.

PMID- 8740734
TI  - Alcohol consumption and risk of colorectal cancer in a cohort of Finnish men.
AB  - We investigated the association between self-reported alcohol ingestion and
      colorectal cancer in a cohort of male smokers in Finland. Among 27,109 men aged
      50 to 69 years, 87 colon and 53 rectal cases were diagnosed during the five to
      eight years of follow-up. Among drinkers, colorectal cancer risk increased with
      the amount of alcohol consumed (P trend = 0.01) with risk increasing by 17
      percent for each drink consumed. Both beer and spirits contributed to this
      increased risk. Further analyses revealed that the positive association with
      alcohol was primarily for colon cancer (P trend = 0.01). Interestingly, risk of
      colorectal cancer associated with drinking (cf self-reported abstinence) changed
      with follow-up time, suggesting an inverse association for alcohol early in
      follow-up, and a positive association after about three-and-a-half years of
      follow-up. Follow-up time did not modify the positive association with amount of
      alcohol among drinkers, however. Results also indicated that beta-carotene
      supplementation may attenuate the effect of alcohol on colorectal cancer risk
      among drinkers. In conclusion, this study supports a role for alcohol in colon
      carcinogenesis and suggests that similar studies should evaluate carefully the
      effects of lifetime drinking habits and recent abstinence.

PMID- 8740735
TI  - The incidence of non-Hodgkin's lymphoma and its histologic subtypes in Asian
      migrants to the United States and their descendants.
AB  - We examined the incidence of non-Hodgkin's lymphoma (NHL) in Chinese, Japanese,
      and Filipino residents of the United States to obtain further clues about the
      etiology of the disease. The age, race, and birthplace of residents of Hawaii,
      San Francisco/Oakland (California), and western Washington who had received a
      diagnosis of NHL during the period 1973-86 were obtained from population-based
      cancer registries, and a special tabulation from the 1980 Census was used to
      estimate the number of person-years at risk for each category of resident. The
      incidence of NHL in each of the Asian groups examined was 35 to 85 percent that
      of US-born Whites. However, there was no consistent trend of increasing incidence
      with increasing generation of residence in any of the groups. In Asian-Americans,
      the risk of small cell lymphocytic and plasmacytoid lymphoma was 10 to 85 percent
      that of Whites, although no clear trends of risk with generation of residence in
      the US were observed. They also were at a reduced risk of follicular lymphoma,
      and in Chinese and Japanese persons, the risk was lower in first generation than
      in later generation migrants (Chinese: Asian-born relative risk [RR] = 0.11, US
      born, RR = 0.84; Japanese: Asian-born, RR = 0.15, US-born, RR = 0.36). The risk
      of diffuse lymphoma was similar in Chinese- and Japanese-Americans and US-born
      Whites. We conclude that, with the exception of follicular lymphoma, the basis
      for the relatively low incidence of NHL in Asian-Americans does not lie in
      exposures or characteristics that differ between the migrants themselves and
      their descendants.

PMID- 8740736
TI  - Cancer incidence among Finnish seafarers, 1967-92.
AB  - A cohort of 30,940 male and 11,529 female seafarers registered in the files of
      Seafarers' Pension Fund in Finland was followed up through the Finnish Cancer
      Registry for cancer in 1967-92. Among male seafarers, there were 1,199 cases of
      cancer, which corresponds to the average cancer incidence in Finnish men. There
      was a statistically significant excess of non-melanoma skin cancer (standardized
      incidence ratio [SIR] = 1.8, 95 percent confidence interval [CI] = 1.2-2.5) and
      mesothelioma (SIR = 2.9, CI = 1.2-5.6) in the follow-up category of 20 or more
      years since the first employment. Alcohol-related cancers were increased among
      seafarers (SIR for cancer of the mouth and pharynx = 1.5; esophagus = 1.4; and
      liver = 1.5; combined CI = 1.1-1.9). Deck crews had a significantly high risk of
      cancer of the pancreas (SIR = 2.0) and also prostate after 10 years since first
      employment (SIR = 1.6). Occupational asbestos exposure among seafarers is likely
      strong enough to cause excess cases of mesothelioma but not of lung cancer.
      Occupational exposures also may be associated with increased risk of cancers of
      the kidney, pancreas, prostate and old-age brain cancer in some of the main
      occupational categories. Cumulative ultraviolet radiation likely doubles the risk
      of non-melanoma skin cancer among older men and repeated sunburns that of skin
      melanoma in ages below 30 (SIR among deck and engine crew = 4.6, CI = 3.1-6.5).
      Female ship personnel had a significantly elevated total cancer risk (observed
      number of cases = 732) which increased over follow-up time (SIR in the category >
      or = 20 years since the first employment was 1.3, CI = 1.1-1.5). This excess was
      attributable primarily to lung cancer (SIR = 2.6, CI = 2.0-3.3). Also cancers of
      the cervix uteri, vulva, and vagina showed significant excess after 10 to 20
      years since first employment aboard.

PMID- 8740737
TI  - Diet and cancers of the larynx and hypopharynx: the IARC multi-center study in
      southwestern Europe.
AB  - The main causes of cancer of the larynx and hypopharynx are smoking cigarettes
      and drinking alcohol. However, for these as well as for other cancers of the
      upper aerodigestive tract, some dietary components, mainly low consumption of
      fruit and vegetables, have been observed to be associated with increased cancer
      risk. We report results from a multicenter case-control study carried out in six
      regions of Europe located in northern Spain, northern Italy, Switzerland, and
      France. A total of 1,147 males with cancer (cases) and 3,057 population controls
      were interviewed on usual diet, lifelong drinking and smoking habits, and
      occupational history. Cancer cases had histologically verified epidermoid
      carcinomas. The cancers were classified in two anatomic sub-entities: the
      epilarynx (hypopharynx and upper part of the larynx), which enters into contact
      with the bolus and the air; and the endolarynx, through which air and tobacco
      smoke pass, but not the bolus. A previous report from this study found that
      alcohol drinking presents a greater risk factor for cancer of the epilarynx than
      for cancer of the endolarynx. The main results regarding diet indicate that high
      intake of fruit, vegetables, vegetable oil, fish, and low intake of butter and
      preserved meats were associated with reduced risk of both epilaryngeal and
      endolaryngeal cancers, after adjustment for alcohol, tobacco, socioeconomic
      status, and non-alcohol energy intake. Among nutrients, a reduced risk was found
      for high intake of vitamins C and E and for a high polyunsaturated/saturated
      fatty acids (P/S) ratio. While these variables are relevant in scoring
      nutritional behaviour, it remains unresolved whether the biologic properties of
      these nutrients play a role in the apparent protective effect.

PMID- 8740738
TI  - Physical activity, obesity, and risk of colorectal adenoma in women (United
      States).
AB  - The relationship between physical inactivity, body mass index (BMI)
      (wt[kg]/ht[m]2), and pattern of adipose distribution with risk of colorectal
      adenomas (precursors of cancer) was examined in 13,057 female nurses in the
      United States, 40 to 65 years of age in 1986, who had an endoscopy between 1986
      and 1992. From 1986 to 1992, 439 participants were newly diagnosed with adenomas
      of the distal colorectum. After controlling for age, prior endoscopy, parental
      history of colorectal cancer, smoking, aspirin, and intakes of animal fat,
      dietary fiber, folate, methionine, and alcohol, physical activity was associated
      inversely with risk of large (> or = 1 cm) adenomas in the distal colon (relative
      risk [RR] = 0.57, 95 percent confidence interval [CI] = 0.30-1.08, comparing high
      and low quintiles of average weekly energy expenditure from leisure-time
      activities; P trend = 0.05). Much of the benefit came from activities of moderate
      intensity such as brisk walking. In addition, BMI was associated directly with
      risk of large adenomas in the distal colon (multivariate RR = 2.21 [CI = 1.18
      4.16], P trend = 0.0001, for BMI > or = 29 cf < 21 kg/m2). Waist circumference
      and the waist-to-hip ratio (WHR) were not related significantly to adenoma
      independently of BMI, but women with both a high BMI and high WHR were at greater
      risk of large colon adenoma (multivariate RR = 1.99, CI = 0.98-4.05) than women
      with high BMI but relatively low WHR (multivariate RR = 1.35, CI = 0.61-2.97).
      BMI was not related to small (< 1 cm) adenoma risk but physical activity had an
      inverse association with small adenomas in the distal colon (multivariate RR =
      0.68, CI = 0.40-1.15, P trend = 0.03). The relationships between BMI or physical
      activity were considerably weaker and inconsistent for rectal adenomas. These
      results, in women, support an inverse association between physical activity and
      occurrence or progression of adenomas in the distal colon; obesity is associated
      with an elevated risk of large adenomas.

PMID- 8740739
TI  - Testicular cancer, cryptorchidism, inguinal hernia, testicular atrophy, and
      genital malformations: case-control studies in Denmark.
AB  - To explore risk factors for testicular cancer and cryptorchidism, two parallel
      case-control studies were conducted in Denmark. The testicular cancer study was
      population-based and included 514 cases and 720 controls. The cryptorchidism
      study included 387 cases and 416 controls and was based on two hospital series of
      men treated for cryptorchidism and a control group sampled among residents in the
      Copenhagen area. The 2,037 men were interviewed by telephone. The relative risk
      (RR) of testicular cancer in men with treated or persisting cryptorchidism was
      3.6 (95 percent confidence interval = 1.8-6.9), but no increase in risk was seen
      in the six to seven percent of the men who reported a history of undescended
      testes that descended spontaneously. The RR in men who were treated for
      cryptorchidism increased with age at treatment. This effect may be due wholly or
      in part to increased treatment of boys with testes that would have descended
      spontaneously if they had not been treated. Cryptorchidism and inguinal hernia
      may be confused and reported interchangeably. In the absence of cryptorchidism or
      testicular atrophy, clinical inguinal hernia was not associated with testicular
      cancer. Testicular atrophy was associated with both testicular cancer and
      cryptorchidism. Associations with other congenital malformations were few and
      based on small numbers.

PMID- 8740740
TI  - Sun exposure, pigmentary traits, and risk of cutaneous malignant melanoma: a case
      control study in a Mediterranean population.
AB  - The main objective of this study was to assess the influence of sun exposure and
      pigmentary traits on the risk of cutaneous malignant melanoma (CMM) in a
      Mediterranean population (Andalusia, southern Spain). Cases and controls were
      selected from 1988 to 1993. The study population included 105 incident cases with
      non-familial CMM (ICD-9 code 172) and 138 controls aged 20 to 79 years. Data were
      collected by personal interview, and melanocytic nevi were counted over the
      entire body surface. Crude, and multiple-risk factor adjusted, odds ratios (OR)
      and their 95 percent confidence intervals (CI) were computed. After adjustment,
      the major constitutional risk factor was skin type I-II (OR = 29.8, CI = 8.9-100)
      compared with skin type V. Statistically significant and positive trends were
      observed between the risk of CMM and occupational sun exposure of the skin (P =
      0.003), recreational exposure (P < 0.001), and cumulative lifetime sun exposure
      (P < 0.001). Several characteristics related to sun exposure during summer
      increased the CMM risk, e.g., episodes of blistering sunburns and the number of
      sunbaths in childhood. Use of sunscreens and spending summer holidays in places
      other than beach were associated with a lower risk of CMM. Regarding pigmentary
      traits, CMM significantly occurred with more frequency in individuals with a high
      degree of freckling and quoted numbers of melanocytic nevi. In conclusion, the
      results support sun exposure and pigmentary traits (skin type, melanocytic nevi,
      and freckles) as main risk factors for CMM in this population.

PMID- 8740741
TI  - Occupational exposure to perchloroethylene.

PMID- 8740742
TI  - Childhood leukemia and social circumstance.

PMID- 8740743
TI  - Myocardial infarction in young adults: risk factors and clinical features.
AB  - To define the risk factors and clinical presentation of patients under age 40 who
      present to the emergency department (ED) of a community hospital with an acute
      myocardial infarction (MI), a retrospective cross-sectional study was conducted
      over a 7-year period. Two hundred and nine consecutive cases of initial MI who
      met World Health Organization criteria (chest pain, ECG changes, and serum enzyme
      rises) and were admitted to one of five participating hospitals were reviewed.
      The mean age of patients was 34.8 years (range, 17-39); 81% were male. The major
      risk factor was tobacco use (81%), followed by family history (40%), hypertension
      (26%), and hyperlipidemia (20%). One hundred and eighty-three patients (87.6%)
      had ECG evidence of cardiac ischemia, injury, or infarction in the ED.
      Approximately 24% of patients had multi-vessel coronary atherosclerosis as
      documented by angiography; 62% had single vessel disease; and 14% had normal
      coronary arteries. The most common anatomical location for the MI was the
      inferior wall. This study characterized the epidemiology of acute MI in young
      adults: 1) smoking emerged as the main coronary risk factor; 2) atherosclerosis
      continues to be the major etiology; 3) a common finding on angiography was single
      vessel disease causing infarction of the inferior wall; and 4) the complication
      rate was comparable to older populations, but the in-hospital mortality was only
      1.9%.

PMID- 8740744
TI  - Adult retropharyngeal abscess: a case report and review of the literature.
AB  - The case of an 18-yr-old otherwise healthy adult with retropharyngeal abscess
      (RPA) presenting with sore throat and syncope is reported. The case illustrates
      that sore throat with symptoms out of proportion to oropharyngeal findings should
      prompt a search for pathology other than simple pharyngitis. A literature search
      for case reports of RPA in adults was done to derive characterizations about this
      disease. Adult RPA patients present with sore throat, dysphagia, neck pain and,
      less commonly, stridor. Adult RPA occurs as a complication of procedures or blunt
      trauma to the neck, or spread of infection from an adjacent focus. The incidence
      of underlying disease causing immunosuppression is high. RPA in adults without
      history of preceding trauma or coexistent illness is unusual.

PMID- 8740745
TI  - Pneumomediastinum presenting as acute airway obstruction.
AB  - Pneumomediastinum is an entity with diverse underlying etiologies and variable
      clinical presentations. We present a case of pneumomediastinum that on initial
      presentation appeared to be an upper airway emergency most consistent with adult
      epiglottitis. The pathophysiology of pneumomediastinum involves extravasation of
      air through perivascular interstitial tissues. Once air has gained access into
      the soft tissues, it may dissect upward into the neck and distend upper airway
      structures. This may cause patients with pneumomediastinum to have symptoms such
      as a sore throat or dysphagia. The patient we describe had such dramatic upper
      airway symptomatology that adult epiglottitis was the initial suspected
      diagnosis, and acute airway intervention was required. The various etiologies,
      presentations, and pathophysiology of pneumomediastinum are discussed.

PMID- 8740746
TI  - Adjunctive dexamethasone therapy for pediatric bacterial meningitis.
AB  - There have been numerous studies performed to assess the impact of adjunctive
      corticosteroid therapy on the outcome of pediatric bacterial meningitis. Much of
      these data are conflicting, which can result in confusion regarding therapeutic
      efficacy. The present article will review the pathophysiology of this disease,
      critique the body of medical literature on this aspect of therapy, and provide
      guidelines for the emergency physician on the use of dexamethasone therapy for
      bacterial meningitis in children.

PMID- 8740747
TI  - An unusual fetal complication of traumatic uterine rupture.
AB  - Rupture of the gravid uterus is reported in less than one percent of women
      involved in motor vehicle accidents. A 22-year-old nulliparous woman at 22 weeks
      gestation was involved in a motor vehicle accident. Evaluation revealed a uterine
      rupture with complete expulsion of placenta and decapitated fetus. Prompt
      surgical intervention and control of hemorrhage allowed preservation of
      fertility.

PMID- 8740748
TI  - Rupture of the gravid uterus secondary to motor vehicle trauma.
AB  - A rare case of gravid uterine rupture secondary to motor vehicle accident trauma
      is presented. The case illustrates the serious risk to the fetus as well as the
      potential for maternal catastrophe with this condition. Normal physiological
      changes in pregnancy hinder the early diagnosis in many cases. A greater
      awareness of this entity along with prompt diagnosis, aggressive resuscitation,
      and surgical intervention will help reduce morbidity and mortality.

PMID- 8740749
TI  - Fatal spontaneous rupture of a gravid uterus: case report and literature review
      of uterine rupture.
AB  - Spontaneous uterine rupture is a life-threatening obstetrical emergency
      encountered infrequently in the emergency department. The diagnosis of
      spontaneous uterine rupture is often missed or delayed, leading to maternal and
      fetal mortality. Emergency physicians must consider this diagnosis when presented
      with a pregnant patient in shock with abdominal pain. We present the case of a 38
      year-old gravid female who presented to the emergency department in cardiac
      arrest 24 hours after an initial complaint of abdominal pain. We review the
      uterine rupture literature with specific focus on risk factors, signs and
      symptoms, diagnosis, treatment, and outcome.

PMID- 8740750
TI  - Iatrogenic magnesium overdose: two case reports.
AB  - We report two cases of iatrogenic intravenous magnesium overdose. Both patients
      presented to the emergency department in alcohol withdrawal, and during the
      course of their therapy were ordered to receive 2 g of magnesium sulfate
      intravenously. The patients were erroneously given 20 g of magnesium sulfate,
      causing cardiac arrest in both cases. The patients were both successfully
      resuscitated. One patient was discharged neurologically intact and the other died
      three days later. Review of the literature identified one previous report of
      iatrogenic overdose of intravenous magnesium causing death. Hypermagnesemia is a
      rare occurrence, particularly in the absence of renal failure. The cause is often
      iatrogenic. The major life-threatening clinical manifestations are cardiac
      conduction delays, asystole, apnea, and coma. A particular hazard of intravenous
      magnesium therapy is the variety of units of measurement used in written orders
      and on drug labels. This can easily lead to errors in drug administration.

PMID- 8740751
TI  - Neuromuscular blocking agents in the emergency department.
AB  - Neuromuscular blocking agents (NMBAs) are utilized frequently in the emergency
      department (ED). We begin with a brief history of neuromuscular blockade, then
      review the indications and guidelines for its use in the emergency department
      setting. The relevant agents will be discussed focusing on dosage, side effects,
      and adverse reactions. Special attention will be paid to succinylcholine, the
      drug most commonly employed in the ED setting, followed by a summary of the
      nondepolarizing agents currently available, in particular the four shorter-acting
      agents that are most appropriate for administration in the ED.

PMID- 8740752
TI  - Another cause of surgical needle holder damage to surgical sutures.
AB  - The sharp edges of the box lock of the needle holder can inadvertently damage the
      suture during instrument ties. Compression of a monofilament nylon suture between
      the sharp edges of the box lock of a surgical needle holder damages the suture,
      reducing its breaking strength. This adverse effect has been eliminated by one
      manufacturer whose needle holder box lock has rounded edges and sufficient space
      to permit passage of the suture.

PMID- 8740753
TI  - A novel method for replacement of the dislodged tracheostomy tube: the
      nasogastric tube "guidewire" technique.
AB  - Unscheduled replacement of dislodged tracheostomy tubes can be a challenging
      procedure for the physician and a frightening event for the patient. Forceful
      attempts at replacement are both painful and dangerous; such attempts may disrupt
      the soft tissues adjacent to the tracheostomy tract, creating a false passage and
      potentiating acute respiratory failure. We describe a technique using a standard
      nasogastric tube that allows safe and precise replacement of tracheostomy tubes
      in both sedated and combative patients under routine and emergent conditions.

PMID- 8740754
TI  - Introduction to the series, "Antibiotic use in the emergency department".

PMID- 8740756
TI  - Severe tophaceous gout.

PMID- 8740755
TI  - Antibiotic use in the emergency department: I. The penicillins and
      cephalosporins.
AB  - The penicillins and cephalosporins are beta-lactam agents that provide broad
      spectrum antimicrobial coverage pertinent to many infectious diseases diagnosed
      in the emergency department. These groups of drugs also have in common their
      classification into subcategories or "generations" that delineate their
      usefulness in specific clinical scenarios such as infections with Gram-positive
      or -negative bacteria, Pseudomonas infections, or febrile neutropenic patients.
      Understanding these subcategories is essential to both efficacious and cost
      effective use of these agents. This article reviews the pharmacology and clinical
      utility of the beta-lactams--including a new class of antibiotics, the
      carbacephams--for the emergency physician.

PMID- 8740757
TI  - Vaginal discharge in the adult: a practice guideline.
AB  - A practice guideline as a preformatted chart is presented. It is designed to be
      simple in concept and design, easy to use, parsimonious of data, easily scanned
      for quality assurance, and to provide clinical and cost-effectiveness prompts. It
      has supporting medical information for all recommendations that is literature-
      and experience-based. A patient aftercare instruction sheet is appended. An
      abbreviated "pocket practice guideline" is also provided. This format is clearly
      appropriate only for simple, not complex, clinical encounters.

PMID- 8740758
TI  - Death from asthma: rare but real.
AB  - Asthma mortality has been increasing over the past 15 years. Since the incidence
      of fatal asthma is rare, death is perceived as an unexpected outcome. This paper
      reviews the nature of asthma, and the circumstances and characteristics of
      patients with fatal asthma attacks. In light of these features, the emergency
      care of acute asthma is discussed. Recommendations for improvement of prehospital
      and hospital care are made. Despite optimum therapy and management, death is
      sometimes unavoidable.

PMID- 8740760
TI  - The future of emergency medicine research.

PMID- 8740759
TI  - Religious freedom and forced transfusion of Jehovah's Witness children.

PMID- 8740761
TI  - The "GI Cocktail" in the evaluation of chest pain in the emergency department.

PMID- 8740762
TI  - Stress in the emergency department clerical staff.
AB  - Clerical staff are vital for the effective management of the emergency
      department. A survey of emergency department clerks was conducted to determine
      the prevalence and types of stress in their jobs. Forty-six of fifty surveys were
      completed and returned. Seventy-six percent of the respondents rated their job in
      the "extremely stressful" range. Stress was a factor responsible for job
      absenteeism in 24% of the respondents. Most agreed that physician education is
      necessary.

PMID- 8740763
TI  - Ethical issues in the forced transfusion of Jehovah's Witness children.
AB  - This paper examines the views of Jehovah's Witnesses in regards to their refusal
      of blood transfusions for themselves and their children. After setting out the
      legal framework society presently has in place for dealing with such refusals,
      the paper reviews the ethics literature that justifies the intervention by the
      State to force the transfusion of Jehovah's Witness children. It is claimed that
      the arguments such literature develops are seriously problematic. A different
      approach is suggested.

PMID- 8740764
TI  - Research directions in emergency medicine: 21-22 January 1995.
AB  - The goal of emergency medicine is to improve health while preventing and treating
      disease and illness in patients seeking emergency medical care. Improvements in
      emergency medical care and the delivery of this care can be achieved through
      credible and meaningful research efforts. Improved delivery of emergency medical
      care through research requires careful planning and the wise use of limited
      resources. To achieve this goal, emergency medicine must provide appropriate
      training of young investigators and attract support for their work. Promotion of
      multidisciplinary research teams will help the specialty fulfill its goals. The
      result will be the improvement of emergency medical care, which will benefit not
      only the patients emergency physicians serve but also, ultimate, the nation's
      health.

PMID- 8740765
TI  - Validation of large data sets, an essential prerequisite for data analysis: an
      analytical survey of the Bone Marrow Donors Worldwide.
AB  - Large data sets like the Bone Marrow Donors Worldwide (BMDW) data set can be used
      for population genetic analyses. The qualities of such data sets are unique. To
      be able to use the BMDW data for analyses, several problems, like limited size
      and selective DR typing, of the data have to be solved and the quality of the
      registry data subsets has to be examined. We describe these problems and methods
      to overcome them. Also, we give an overview of the qualities of the different
      registry subsets. Sixteen of the twenty-nine examined subsets contain data that
      can be used for population genetic analysis. We will deal with these analyses in
      the future. Additionally, we present a method to calculate the minimum number of
      individuals required for reliable haplotype frequency estimation.

PMID- 8740766
TI  - Novel HLA-B alleles, B*8201, B*3515 and B*5106, add to the complexity of
      serologic identification of HLA types.
AB  - Three class I alleles, B*8201, B*3515 and B*5106, have been described using DNA
      and cDNA sequencing. The B*8201 allele is most structurally related to B*5602,
      differing from it by 14 nucleotide substitutions resulting in 5 amino acid
      differences. The other two alleles, B*3515 and B*5106, differ from their most
      closely related HLA-B alleles by 2-3 nucleotide substitutions resulting in 1-2
      amino acid substitutions, respectively. The majority of nucleotide substitutions
      marking these new alleles are observed in other HLA-B alleles suggesting that
      gene conversion and/or reciprocal recombination have created this diversity. All
      of the amino acid substitutions are predicted to alter the antigen binding site
      of the HLA-B molecule. The newly defined HLA-B allelic products were originally
      defined by their unusual serologic reactivity patterns. The B*8201 allelic
      product is serologically typed as a B "blank" or as a variant of B22 or B45.
      These patterns and the serologic reactivity of the other newly described allelic
      products are consistent with the protein sequence homology among specific HLA-B
      molecules. While serology remains a powerful tool for detecting HLA diversity,
      alleles generated by events resulting in the sharing of HLA sequence
      polymorphisms among alleles at a locus will continue to create complexity in the
      interpretation of typing results.

PMID- 8740767
TI  - HLA*A2 confers mortality risk for cardiovascular disease in Pimans.
AB  - A sample of 1465 full heritage Piman Indians from Arizona were typed for the
      serological antigens of the HLA class I loci and then incorporated into a
      survival study that ended December 31, 1991. The total follow-up time was 11,749
      person-years with an average of 8.0 years per person. During the study 298
      persons died, 54 from cardiovascular disease (CVD). Allele HLA*A2 conferred a
      4.94 fold rate for death from CVD (95% C.I. 1.91-12.77). When controlled for the
      potential confounding variables, cholesterol, mean blood pressure, smoking, body
      mass index, rheumatoid factor titer, and nephropathy, the mortality rate ratio
      (MRR) was 5.42 (95% C.I. 1.98-14.82). There was no statistically significant
      association of mortality with other HLA-A or HLA-B alleles, or for causes of
      death not related to cardiovascular disease.

PMID- 8740768
TI  - HLA-A, -B, -C, -DR, -DQ typing in a population group of Senegal: distribution of
      HLA antigens and HLA-DRB1*13 and DRB1*11 subtyping by PCR using sequence-specific
      primers (PCR-SSP).
AB  - One-hundred-and sixteen Senegalese Serere were typed for HLA antigens and
      compared with other ethnic groups in Gambia. We did not find significant
      differences (Fisher's exact test; P < 0.01) in the HLA antigens distribution
      between the Serere and Mandinka groups in Senegal and the Serere, Mandinka and
      Wolof in The Gambia. The most common HLA haplotypes found (P < 0.01; Chi square
      with Yates' correction) were: A1, B8; A2, B51; A32, B44; A33, B58; A2, Cw2; A2,
      Cw4; A33, Cw3; A2, DR17; A10, DR10; B35, Cw4; B53, Cw6; B57, Cw3; B65, Cw8; B50,
      DR15; B52, DR4; Cw2, DR17; DR7, DQ2; DR18, DQ4. The HLA-DRB1*13 and DRB1*11
      alleles were subtyped by PCR-SSP and the frequencies of these alleles in the
      studied population given. HLA-DRB1*1304 and DRB1102 were the most common alleles
      found respectively 15.0 and 18.5%.

PMID- 8740769
TI  - Complement C4A, C4B and BF haplotypes in Koreans.
AB  - Specific alleles at C4A, C4B and BF loci occur in populations and are inherited
      in complotypes, which are linked with particular HLA haplotypes. Considerable
      differences in complement allele and complotype frequencies have been observed
      among various ethnic groups. In the present study, 109 Korean families were
      analyzed for complement and complotype polymorphism. Thirty-four different
      complotypes were detected: the most common was BF*S-C4A*3-C4B*1 (S31) with a
      frequency of 42.2%, followed by S42 (14.3%) and F31 (13.8%). Three complotypes,
      S42, F31, and FQ01, showed positive linkage disequilibrium. Some of the
      complotypes were linked with characteristic HLA haplotypes. Two complotypes
      carrying duplicated C4A genes, S3+31(BF*S-C4A*3-C4A*3-C4B*1) and S3+2Q0(BF*S
      C4A*3-C4A*2-C4B*Q0), were exclusively associated with HLA-A24-Cw7-B7-DR1-DQ1 and
      A24-CBL-B52-DR15-DQ1 haplotypes, respectively. Twelve families showed recombinant
      haplotypes, nine in the class I region, three between the HLA-B and HLA-DR loci,
      and none in the class III region. Maternal recombination occurred twice as
      frequently as paternal. The results obtained in this study represent the
      frequencies of complotypes and extended HLA haplotypes of well-defined Koreans,
      based on a family study.

PMID- 8740770
TI  - The role of HLA antibodies in neonatal thrombocytopenia: a prospective study.
AB  - The role of HLA antibodies in neonatal alloimmune thrombocytopenia is
      controversial. We prospectively studied the sera of obstetric patients at
      delivery for HLA antibodies and correlated their presence with umbilical cord
      blood platelet counts. We studied 493 births at The Johns Hopkins Hospital
      comprising of 357 African American, 115 Caucasian, and 21 babies of other racial
      groups. One hundred and thirty nine mothers had HLA antibodies. Of these HLA
      alloimmunized mothers, only ten infants had platelet counts of 150,000/ microL or
      less. Three hundred and eight mothers with no detectable antibodies gave birth to
      27 infants with platelet counts of 150,000/microL or less. Yates corrected Chi
      square analysis showed no significant relationship between maternal HLA
      alloimmunization and baby platelet count (p = 0.709). Only 8 of sixty cord sera
      from babies of HLA alloimmunized mothers were positive for HLA antibodies. The
      HLA cord blood antibody results were then correlated with the neonatal platelet
      counts. The Fisher's exact test showed no significant relationship between the
      presence of HLA antibodies in cord blood samples and neonatal platelet counts (p
      = 0.232). Although one third (31%) of mothers have HLA antibodies, neonatal
      thrombocytopenia is rarely associated with this finding. However, HLA antibodies
      can cross the placenta, and in these unusual cases, may be associated with a
      higher risk of neonatal thrombocytopenia.

PMID- 8740771
TI  - Rapid allelic diversification and intensified selection at antigen recognition
      sites of the Mhc class II DPB1 locus during hominoid evolution.
AB  - The evolution of polymorphism at the Mhc class II DPB1 locus was studied by
      comparison of chimpanzee (Pan troglodytes), pygmy chimpanzee (Pan paniscus),
      gorilla (Gorilla gorilla) and human DPB1 alleles. Extensive polymorphism was
      found in all hominoids. The clustering of sequences in the phylogenetic tree is
      consistent with rapid generation of the DPB1 polymorphism. Analysis of the
      substitution pattern for human alleles shows an excess of non-synonymous changes
      to synonymous changes at antigen recognition sites, indicating that the amino
      acid polymorphism at these sites is being maintained by selection. By contrast,
      no excess of nonsynonymous changes was found at the antigen recognition sites of
      nonhuman hominoid species. Thus, it appears that diversifying selection on the
      DPB1 polymorphism has intensified in the lineage leading to humans. No evidence
      was found for the existence of ancient allelic lineages predating the divergence
      of the hominoid species. The number of synonymous differences among DPB1 alleles
      is lower than among DQB1 and DRB1 alleles, indicative of a more recent origin for
      the DPB1 polymorphism and consistent with the more rapid evolution suggested by
      the phylogenetic tree.

PMID- 8740772
TI  - Primate DRB6 gene expression and evolution: a study in Macaca mulatta and
      Cercopithecus aethiops.
AB  - DRB6 has been found to be transcribed in human and apes. Promoter region and exon
      1 come from a 5' LTR from a mammary tumour retrovirus. However, the putative
      protein structure would be very different to other DR molecules and it is
      doubtful that it may function as an antigen presenting molecule. Primate DRB6
      alleles previously published together with the two new macaque sequences reported
      here support the existence of a strong selective pressure working on exon 2 to
      generate stop codons at the end of the exon (between codons 74 and 94) during at
      least 23 million years. The topology of dendrograms constructed with different
      primate DRB6 alleles supports the "trans-species" evolution proposed for MHC
      class I, class II and possibly C4 genes. Finally, DRB6, which is one of the
      oldest DRB genes, has been lost in the HLA-DRB3 (or DR52) group of haplotypes
      (DR3, DR5, DR6 and DR8) and a small DRB6 sequence is present at the exon 2 first
      hypervariable region of DRB4 (or DR53) gene, which is present in DR4, DR7 and DR9
      haplotypes.

PMID- 8740773
TI  - Molecular analysis of HLA DRB1 and DQB1 in Italian patients with pemphigus
      vulgaris.

PMID- 8740774
TI  - HLA-DQB1 upstream regulatory region polymorphism and type I diabetes.

PMID- 8740775
TI  - A comprehensive PCR-SSP typing system for identification of HLA-A locus alleles.

PMID- 8740776
TI  - Detection of the DRB4 null gene, DRB4*0101102N, by PCR-SSP and its distinction
      from other DRB4 genes.

PMID- 8740777
TI  - Allelic variations in the TAP2 and LMP2 genes in Behcet's disease.

PMID- 8740778
TI  - HLA-B14 subtypes and their influence on allorecognition.

PMID- 8740779
TI  - Evolutionarily conserved transcription regulatory elements within the 5'-flanking
      region of the human CD5 gene.

PMID- 8740780
TI  - Cord blood transplants raise hopes, concern in the U.S.

PMID- 8740781
TI  - Quality of life: a central issue in AIDS and cancer.

PMID- 8740782
TI  - Effects of adjuvant systemic treatments in breast cancer.

PMID- 8740783
TI  - Cyclin D1, another molecule of the year?

PMID- 8740784
TI  - 1975-1995 revised anti-cancer serological response: biological significance and
      clinical implications.
AB  - In the 1970s a considerable amount of work was carried out in an attempt to
      identify an anti-tumor serological response in cancer patients. These analyses
      have not been very informative due to the complexity and heterogeneity of the
      response. More recently, the availability of recombinant molecules, synthetic
      peptides and analytic and semi-quantitative assays has enabled a better
      dissection of humoral immunity. Antibodies against intracellular antigens (c-myb,
      c-myc, p53 and p21 ras) have been found in a significant, albeit varying,
      proportion of patients bearing various tumors. Association with a poor prognosis
      is documented for anti-p53 antibodies in breast carcinoma patients. A number of
      cell surface antigens, including mucins, oncoproteins and carbohydrate antigens
      have been found to elicit a humoral immune response and, in some instances,
      circulating immune complexes were observed. A protective role for or, on the
      other hand, masking effects of such antibodies is still controversial. An
      indication that a serological response can be beneficial comes from vaccination
      studies. A significant association between the development of an anti-tumor
      antigen antibody response and prolonged survival was observed following
      vaccination of melanoma patients with GM2 or anti-idiotypic antibodies which
      molecularly mimic tumor-associated antigens. It is to be hoped that in the near
      future the numerous ongoing immunization trials and prognostic studies
      demonstrate whether antibody response can exert a protective role in vivo.

PMID- 8740785
TI  - Are hematopoietic colony-stimulating factors useful in association with
      chemotherapy in the treatment of HIV-related non-Hodgkin's lymphomas?

PMID- 8740786
TI  - Risk of new primaries after chemotherapy and/or tamoxifen treatment for early
      breast cancer.
AB  - BACKGROUND: Both chemotherapy and tamoxifen are widely used either alone or in
      combination as adjuvant treatment following mastectomy. Despite the fact that
      both of them exhibit carcinogenic properties in experimental models, detailed
      reports on the incidence of new primaries following chemotherapy and/or tamoxifen
      in patients with early breast cancer are limited. PURPOSE: To investigate the
      incidence of new primaries (including opposite breast tumors and skin cancers) in
      untreated patients and in patients treated with either tamoxifen or chemotherapy
      or with both modalities. PATIENTS AND METHODS: A total of 1696 patients with
      early breast cancer, 1286 of whom were treated with either CMF-based adjuvant
      chemotherapy (n = 410), tamoxifen (n = 656) or with a combination of the two (n =
      220) were considered for the present analysis. Patients were operated on between
      November 1983 and December 1991 and were followed up to June 1994. Detailed
      information about second malignancies were available for all patients. RESULTS:
      Overall, 53 new primaries, 19 of them opposite breast tumors, occurred in 53
      patients. The actuarial cumulative incidence rates at 5 years were: 3.1% (95% CI:
      1.4%-4.8%) in untreated patients; 1.7% (95% CI: 0.0%-3.5%) in tamoxifen-treated
      patients; 4.2% (95% CI: 1.3%-7.1%) in chemotherapy-treated patients and 2.6% (95%
      CI: 0.0%-5.2%) in the chemo-tamoxifen group (all groups: P = n.s.; chemotherapy
      treated versus tamoxifen-treated: P = 0.01). The corresponding figures, after
      exclusion of the patients with opposite-breast and skin tumors, were: untreated
      patients: 2% (95% CI: 0.6%-3.4%); tamoxifen-treated patients: 0.95% (95% CI: 0.0%
      2.4%); chemotherapy-treated patients: 2.6% (95% CI: 0.4%-4.8%); chemotherapy plus
      tamoxifen: 1.65% (95% CI: 0.4%-3.8%); (all groups: P = n.s.; CT versus TAM P =
      0.05). Chemotherapy-treated patients showed a risk that was about two-fold that
      of the one to be expected in the general population. By contrast, a decrease in
      the total risk was observed in patients treated with tamoxifen. Patients who
      received chemotherapy and tamoxifen as well as those in the no-treatment group
      showed a risk which was comparable to that of the general population.
      CONCLUSIONS: Adjuvant chemotherapy appears to increase the risk of second
      malignancies. By contrast, tamoxifen seems to exert an overall protective effect
      in this regard, and it also appears to counteract, at least partially, the
      carcinogenic effect of chemotherapy. IMPLICATIONS: While there is plenty of
      evidence that the benefit achieved by adjuvant chemotherapy considerably exceeds
      the risk of second malignancies, the indiscriminate use of chemotherapy should be
      avoided, particularly in patients with a low risk of relapse. Moreover, it seems
      reasonable to prefer tamoxifen over chemotherapy for patients likely to obtain
      comparable therapeutic benefit from antiestrogenic treatment.

PMID- 8740787
TI  - The effect of adjuvant prednisone combined with CMF on patterns of relapse and
      occurrence of second malignancies in patients with breast cancer. International
      (Ludwig) Breast Cancer Study Group.
AB  - BACKGROUND: The addition of low-dose prednisone (p) to the adjuvant regimen of
      cyclophosphamide, methotrexate, 5-fluorouracil (CMF) allowed patients to receive
      a larger dose of cytotoxics when compared with those on CMF alone. However,
      disease-free survival and overall survival were similar for the two groups. To
      test the hypothesis that low-dose prednisone might influence the efficacy of the
      cytotoxic regimen used, the toxicity profiles of the two treatment regimens and
      the patterns of treatment failure (relapse, second malignancy, or death) were
      examined. PATIENTS AND METHODS: 491 premenopausal and perimenopausal patients
      with one to three positive axillary lymph nodes included in International
      (Ludwig) Breast Cancer Study Group (IBCSG) trial I from 1978 to 1981 and
      randomized to receive CMF or CMFp were analyzed for differences in long-term
      outcome and toxic events. The 250 patients assigned to CMF and prednisone
      received on the average 12% more cytotoxic drugs than those who received CMF
      alone. RESULTS: The 13-year DFS for the CMFp group was 49% as compared to 52% for
      CMF alone, and the respective OS percents were 59% and 65%. Several toxic effects
      such as leukopenia, alopecia, mucositis and induced amenorrhea were reported at a
      similar incidence in the two treatment groups. Using cumulative incidence
      methodology for competing risks, we detected a statistically significant increase
      in first relapse in the skeleton for the CMFp group at 13 years follow-up with a
      relative risk (RR) of 2.06 [95% confidence interval (CI), 1.23 to 3.46; P =
      0.004]. Patients with larger tumors in the CMFp regimen were especially subject
      to this increase with a RR for failure in the skeleton of 3.32 (95% CI, 1.57 to
      7.02; P = 0.0005). CMFp-treated patients also had a larger proportion of second
      malignancies (not breast cancer), with RR of 3.34 (95% CI, 0.91 to 12.31; P =
      0.09). CONCLUSIONS: Low-dose continuous prednisone added to adjuvant CMF
      chemotherapy enabled the use of higher doses of cytotoxics. This increased dose
      had no beneficial effect on treatment outcome, but was associated with an
      increased risk for bone relapses and a small, not statistically significant
      increased incidence of second malignancies. The effects of steroids, which are
      widely used as antiemetics (oral or pulse injection) together with cytotoxics,
      should be investigated to identify their influence upon treatment outcome.

PMID- 8740788
TI  - Involvement of the CCND1 gene in hairy cell leukemia.
AB  - BACKGROUND: Previous results suggested increased mRNA expression of CCND1 in
      hairy cell leukemia (HCL). The CCND1 gene is involved in the t(11;14)(q13;q32)
      chromosomal rearrangement, a characteristic abnormality in mantle cell lymphoma
      (MCL). We and others reported that, in contrast to other B-cell lymphomas, almost
      all MCL have over-expression of the CCND1 gene with a good correlation between
      RNA and protein analysis. Recent studies showed that overexpression of the cyclin
      D1 protein can be easily detected by immunohistochemistry (IHC) on formalin
      fixed, paraffin embedded tissues. PATIENTS AND METHODS: To investigate whether
      the CCND1 gene is involved in HCL, we performed IHC on a series of 22 cases using
      formalin-fixed paraffin embedded splenectomy specimens. For IHC the sections were
      boiled in citrate buffer. The presence of rearrangements within the BCL-1 locus
      and the CCND1 gene was analyzed in 13 of 22 cases by Southern blot analysis using
      all available break-point probes. Expression of CCND1 was analyzed at the mRNA
      level (Northern blot) and protein level (IHC). RESULTS: Overexpression of the
      cyclin D1 protein using IHC was observed in all cases, with strong expression in
      5 cases. Pre-existing B- and T-cell areas of the spleen did not express
      significant levels of the cyclin D1 protein. Seven of 9 cases analyzed by both
      IHC and Northern blotting showed overexpression of the CCND1 gene with both
      methods. No genomic abnormalities were observed in any of the 13 cases studied by
      Southern blot analysis. Additionally, no 11q13 abnormalities were detected by
      banding analysis of 19 of 22 cases. CONCLUSIONS: The elevated levels of CCND1
      mRNA and protein in conjunction with the absence of overt rearrangements within
      the BCL-1 locus distinguish HCL from MCL and other B-cell malignancies. This
      suggests that activation of the CCND1 gene in HCL is due to mechanisms other than
      chromosomal rearrangement.

PMID- 8740789
TI  - Cardiopulmonary sequelae after treatment for Hodgkin's disease: increased risk in
      females?
AB  - BACKGROUND: The treatment of Hodgkin's disease (HD) involves irradiation and
      chemotherapy. Both modalities may cause heart and lung injury. We aimed to assess
      1) the occurrence of such injury, 2) the extent to which combined versus single
      organ-affection resulted in disability, and 3) whether determinants for
      cardiopulmonary injury could be identified. PATIENTS AND METHODS: A national
      cohort (n = 116) of HD patients (mean age 37 +/- 7 (SD) years, 67 males) was
      examined by interview, echocardiography, bicycle exercise test and lung function
      tests, 5-13 years after mediastinal irradiation with or without chemotherapy.
      RESULTS: Cardiac, pulmonary or combined sequelae occurred, respectively, in 21%,
      15% and 19% of the patients affecting 75% of the females versus 41% of the males
      (P < 0.001). Of the patients with combined sequelae, 27% were disabled versus 4%
      of the rest (P < 0.05). Combined sequelae was associated with dyspnoea (P <
      0.001) and reduced maximal exercise heart rate (P < 0.05). Compared to males,
      females had an increased risk of heart valve regurgitation (46% versus 16%, P <
      0.001), pericardial thickening (22% versus 10%, P = 0.07) and reduced gas
      transfer (41% versus 22%, P = 0.03). Female gender was a significant risk factor
      for cardiac and/or pulmonary sequelae (OR 6.1, 95% CI 2.4-15.7), whereas age,
      follow-up period, smoking habits, histology, bulky mediastinal disease, radiation
      dose and chemotherapy were not. Mean exercise work capacity and O2-saturation
      were within normal limits. CONCLUSIONS: Although cardiac and/or pulmonary
      sequelae were detected in more than half of the patients, only combined injury
      was associated with disability, dyspnoea and reduced performance. Females had an
      increased risk of cardiopulmonary sequelae, which could not be explained by
      treatment-related differences between the genders.

PMID- 8740790
TI  - Hodgkin's disease following solid organ transplantation.
AB  - BACKGROUND: The incidence of second malignancies is markedly increased following
      transplantation of solid organs. However, the development of Hodgkin's disease
      has been described relatively infrequently in this setting, and there is little
      clinical information on these patients and few details on management. PATIENTS
      AND METHODS: We have reviewed the pathologic specimens and clinical history of
      four patients who developed Hodgkin's disease following transplantation of solid
      organs. RESULTS: Hodgkin's disease appeared 26-68 months following
      transplantation of the kidney (2 cases), liver, and heart. Three cases
      demonstrated evidence of Epstein-Barr virus (EBV) in Reed-Sternberg cells. One
      case appears to have arisen after a previous EBV-driven polymorphous
      lymphoproliferation. Hodgkin's disease was localized in three cases and
      disseminated in one. All patients achieved remission with standard therapy and
      continue in remission between 9 and 61 months after therapy. Graft function was
      preserved in all patients. CONCLUSION: Hodgkin's disease occurring in the post
      transplantation period should probably be treated like Hodgkin's disease in non
      immunosuppressed patients. Prolonged disease-free survival is possible and
      function of the transplanted organ can be preserved.

PMID- 8740791
TI  - Primary carcinoma of the fallopian tube. A retrospective analysis of 47 patients.
AB  - BACKGROUND: Fallopian tube carcinoma is a rare disease, and few data about
      prognostic factors are available in the literature. PATIENTS AND METHODS: The
      medical charts of 47 patients with primary carcinoma of the fallopian tube
      treated at our institution between 1982 and 1994 were reviewed. Age, stage,
      histologic grade, residual disease after surgery, peritoneal cytology and lymph
      node involvement were evaluated for their prognostic impact in a univariate
      analysis. RESULTS: The mean age of the patients was 57.5 years and 19 of them
      (40%) had early-stage disease. Poorly differentiated tumors were diagnosed in 64%
      of the patients. Eleven of 20 patients (55%) submitted to surgical evaluation of
      lymph nodes had retroperitoneal involvement. Thirty-three patients received CAP
      chemotherapy following surgery, and the overall clinical response rate was 80%.
      Sixteen patients (34%) had recurrences within 8 to 50 months from diagnosis.
      Twenty patients (42.6%) are alive without disease, one patient is alive with
      tumor, and 26 patients (55.3%) died of the disease. The median survival for the
      group as a whole was 44 months, and the actuarial 5-year survival was 29%. In
      univariate analysis stage (I + II vs. III + IV), grade (G1 + G2 vs. G3) residual
      disease after surgery (less than 2 cm vs. greater than 2 cm). peritoneal cytology
      (negative vs. positive) and lymph-node metastases were all factors significantly
      affecting survival. CONCLUSIONS: Aggressive cytoreductive surgery followed by
      platin-based chemotherapy offer the possibility of long-term control of primary
      tubal carcinoma.

PMID- 8740793
TI  - Critical factors for optimizing the 5-fluorouracil-folinic acid association in
      cancer chemotherapy.
AB  - BACKGROUND: The 5-fluorouracil (FU)-folinic acid (FA) association has
      demonstrated clinical efficacy in colorectal cancer, both in adjuvant and
      metastatic situations. However, there is no clear consensus about the optimal FU
      FA schedule and dose. In addition, it would be of interest to identify FU-FA
      responsive tumors. DESIGN: Our purpose was to review preclinical and clinical
      data dealing with prediction of FU-FA sensitivity and optimization of FU-FA
      schedules. RESULTS: Preclinical studies have highlighted the importance of
      thymidylate synthase (TS), the cellular target of the FU-FA mechanism of action,
      for predicting FU sensitivity. It appears that the more sensitive cell lines
      express the lowest TS activity. Interestingly, the cell lines sensitive to FA
      supplementation are those more sensitive to FU. The role of TS in FU-FA
      responsiveness has been clearly demonstrated in patients with colorectal and
      gastric cancers. Preliminary in vitro and clinical data have shown that the
      folylpolyglutamate synthetase (FPGS), the enzyme responsible for folate
      polyglutamylation, is another promising tool for identifying FU-FA-responsive
      tumors. So far, results of clinical trials do not form a clear consensus
      regarding the need to administer high FA doses for improving FU-FA treatment.
      Experimental studies on human cancer cell lines have demonstrated the wide
      variability among cell lines, ranging from 0.05 to 200 microns, of 1 FA
      concentrations required for maximal FU potentiation. In addition, pharmacokinetic
      studies have reported a significant variability of active folates in plasma after
      administration of standard-dose FA. Altogether, these observations favour high
      dose FA administration to achieve high folate concentrations in plasma and thus
      to counteract the variability of the 1 FA concentrations required. With respect
      to the choice of FU-FA schedule, it appears from experimental data that
      increasing the duration of exposure to FA enhances FU-FA cytotoxicity, probably
      through an increased formation of reduced folate polyglutamate forms. Considering
      the S-phase specificity of FU cytotoxicity as well as its rapid elimination from
      plasma, a schedule of prolonged exposure to both FU and FA should be considered
      preferable. CONCLUSIONS: Results of the new FU-FA administration schedules such
      as the one consisting of a 2-hour FA administration followed by a combination of
      FU bolus and FU infusion, or the chronomodulated FU-FA infusion, open up
      promising approaches for improving the therapeutic index of FU-FA chemotherapy.
      Finally, future clinical studies should investigate tumoral parameters
      pharmacologically linked to FU-FA sensitivity such as pre-treatment TS and FPGS
      activities. Such tumoral investigations along with FU and FA pharmacokinetic
      investigations should provide a better understanding of inter-patient variability
      in response to FU-FA therapy and an optimal management of this chemotherapy
      regimen.

PMID- 8740792
TI  - Optimum anti-emetic therapy for cisplatin induced emesis over repeat courses:
      ondansetron plus dexamethasone compared with metoclopramide, dexamethasone plus
      lorazepam.
AB  - BACKGROUND: This study was undertaken to compare the efficacy and tolerability of
      ondansetron plus dexamethasone (O + D) with metoclopramide plus dexamethasone
      plus lorazepam (M + D + L) over three consecutive courses of cisplatin
      chemotherapy. PATIENTS AND METHODS: This was an international, multicentre,
      double-blind, double-dummy, parallel group study. O+D patients were randomised to
      receive ondansetron 8 mg intravenously (i.v.) plus dexamethasone 20 mg i.v. prior
      to cisplatin (50-100 mg/m2) chemotherapy. On the following 4 days they were
      treated with ondansetron 8 mg bd orally and dexamethasone 4 mg bd orally. M + D +
      L patients were randomised to receive metoclopramide 3 mg/kg i.v., dexamethasone
      20 mg i.v. and lorazepam 1.5 mg/m2 i.v. (max 3 mg) prior to cisplatin
      chemotherapy and a further dose of metoclopramide 3 mg/kg i.v. approximately 2
      hours following the first dose of metoclopramide. Treatment for the following 4
      days was metoclopramide 40 mg tds and dexamethasone 4 mg bd orally. Two hundred
      and thirty-seven patients were recruited into the study (117 patients received O
      + D and 120 received M + D + L). RESULTS: On the first course chemotherapy, O + D
      was significantly superior to the M + D + L regimen for complete control of
      emesis (days 1-5, 54% versus 37%, respectively, P = 0.014). This was maintained
      over the three treatment cycles; 38% of O + D and 20% of M + D + L patients
      remained free of emesis (P = 0.003). Maintenance of control of nausea grade as
      none or mild on days 1-5 over the three courses was significantly better in the O
      + D group (48%) than in the M + D + L (26%, P = 0.003). The most commonly
      occurring adverse events in the O + D group were constipation (25%) and headache
      (19%). In the M + D + L group drowsiness (38% of patients), malaise/fatigue (16%
      of patients), constipation (13% of patients), anxiety (11% of patients) and
      dizziness (10% of patients) were the most commonly reported adverse events.
      Extrapyramidal symptoms were reported by 20% of patients in the M + D + L group.
      Despite the inclusion of lorazepam, 14% of patients in the M + D + L group were
      withdrawn from the study due to extrapyramidal symptoms, which in the opinion of
      the investigators, were probably or almost certainly related to study medication.
      CONCLUSION: This study show that O + D is significantly more effective and better
      tolerated than M + D + L for the control of emesis and nausea over a series of
      three courses of cisplatin chemotherapy.

PMID- 8740794
TI  - Pharmacokinetics, metabolism and tumour disposition of 8-chloroadenosine 3',5'
      monophosphate in breast cancer patients and xenograft bearing mice.
AB  - BACKGROUND: 8-Chloroadenosine 3',5'-monophosphate (8-Cl-cAMP) is undergoing phase
      I clinical trials as an anticancer drug. However, there is debate as to whether
      it is a prodrug for its 8-Cl-adenosine metabolite. DESIGN: Pharmacokinetics,
      metabolism and tumour disposition studies have been performed in 7 breast cancer
      patients receiving continuous infusion (28 day) 8-Cl-cAMP (0.54 or 1.08
      mg/kg/day) and tumour biopsies were obtained before and on the last day of
      infusion. Parallel studies were performed in nude mice bearing the HT29 human
      colon cancer xenograft after continuous infusion (7 day) of active drug doses (50
      or 100 mg/kg/day). RESULTS: Steady state plasma levels (Css) of 8-Cl-cAMP in
      patients ranged from 0.15-0.72 microM but 8-Cl-adenosine was not detected in
      plasma. In contrast, 8-Cl-cAMP was not detectable in 3 tumour biopsies but 8-Cl
      adenosine was present in 2 samples at high concentrations (1.33 and 2.02 microM).
      In mice, Css of 8-Cl-cAMP ranged from 3.2-4.6 microM and 8-Cl adenosine was
      present in plasma only at the higher dose (100 mg/kg/day, peak concentration of
      2.3 microM). In the HT29 xenograft, 8-Cl-cAMP levels were considerably lower than
      in plasma (0.37-1.22 microM) while 8-Cl-adenosine was present at 5.3-21.0 microM
      and 8-Cl-AMP was found at 11.3-35.7 microM. CONCLUSIONS: The fate of 8-Cl-cAMP in
      human tumours is characterised by extensive metabolism to products which are not
      generally observed in plasma. These data raise the possibility that 8-Cl-cAMP is
      a prodrug for a product of its metabolism in human tumours.

PMID- 8740795
TI  - Reverse transcriptase-polymerase chain reaction for expression of tyrosinase to
      identify malignant melanoma cells in peripheral blood.
AB  - BACKGROUND: Circulating tumour cells in the peripheral blood may be important for
      haematogenous spread of disease. The detection of these cells may therefore be a
      poor prognostic indicator. Reverse-transcriptase polymerase chain reaction (RT
      PCR) of target tumour-specific protein expression has been used as a sensitive
      and specific method for the detection of these tumour cells. Initial reports by
      our laboratory and other suggested RT-PCR amplification of the enzyme tyrosinase
      is a useful method for detection of melanoma cells in peripheral blood [1-3].
      PATIENTS AND METHODS: In this report, we have evaluated the application of RT-PCR
      for tyrosinase mRNA as a detection method for melanoma cells in a series of 24
      patients with advanced, metastatic malignant melanoma. A single round RT-PCR
      method is described. RESULTS: The single round RT-PCR was as sensitive as
      previously described nested PCR methods, and had the advantage of reduced
      contamination risks. Blood samples from three out of the twenty-four patients
      were positive. CONCLUSIONS: The frequency of tumour cell detection in peripheral
      blood from patients with advanced disease was lower than previously reported. It
      may be only small numbers of circulating tumour cells are present at any one time
      in the peripheral blood of patients with malignant melanoma. If this is the case
      increased sampling will improve detection frequency. Alternatively, dissemination
      of melanoma through peripheral blood may be a rare event. In our experience, RT
      PCR for tyrosinase mRNA as a staging test for melanoma patients must be
      interpreted cautiously.

PMID- 8740796
TI  - The role of surgery in small-cell lung cancer: a case history.

PMID- 8740797
TI  - Phase I study of paclitaxel (Taxol) and ifosfamide in previously untreated
      patients with advanced non-small-cell lung cancer. A study of the National Cancer
      Institute of Canada Clinical Trials Group.
AB  - BACKGROUND: Paclitaxel (Taxol) and ifosfamide are among the most active single
      agents for the treatment of non-small-cell lung cancer. We undertook this phase I
      dose escalation study to determine the maximum tolerated doses of these drugs
      which could be administered without growth factors to untreated patients with
      tumours of this type. PATIENTS AND METHODS: Forty patients with advanced non
      small-cell lung cancer were treated with a 3-hour infusion of paclitaxel and a 1
      hour infusion of ifosfamide every 3 weeks. Groups of 3 patients were entered at
      escalating dose levels in traditional phase I design. Starting doses were
      paclitaxel, 100 mg/m2, and ifosfamide 3 g/m2, and all patients received
      premedication with dexamethasone, diphenhydramine and a 5-HT3 blocker. Dose
      escalation occurred only after full toxicity assessment for 2 cycles for all
      patients in the dose level. RESULTS: Dose escalation of paclitaxel continued to
      225 mg/m2 without dose-limiting toxicity, but further escalation was not
      attempted because of the known likelihood of neuro-toxicity above this level.
      Instead, ifosfamide was increased to 4 g/m2 for the final level. At these doses,
      dose-limiting myelosuppression was not seen, and there was only 1 episode of
      febrile neutropenia in 164 treatment cycles. Drug-related toxicities of
      ifosfamide included gross hematuria and confusion in 1 patient each, and
      paclitaxel-related symptoms included flu-like syndrome in most patients, mild to
      moderate arthralgia and/or myalgia in 8 and 25 patients, respectively,
      parasthesiae in 15 patients and mild to moderate hypersensitivity reactions in 15
      patients each. Partial response was seen in 20.5% of patients (CI 9.3%-36.5%).
      SUMMARY: Out-patient paclitaxel given over 3 hours and single-dose ifosfamide
      over 1 hour may be combined safely without the need for hematopoietic growth
      factors for the treatment of patients with non-small-cell lung cancer. The
      recommended doses for phase II study are paclitaxel, 225 mg/m2 and ifosfamide, 4
      g/m2 every 3 weeks.

PMID- 8740798
TI  - Ifosfamide plus paclitaxel in advanced non-small-cell lung cancer: a phase I
      study.
AB  - BACKGROUND: Ifosfamide and paclitaxel are active drugs in the management of non
      small-cell lung cancer. We have performed a phase I study using a fixed dose of
      ifosfamide with escalating doses of paclitaxel, with G-CSF support, in an effort
      to determine the maximum tolerated dose (MTD) of paclitaxel in this combination,
      and to describe the dose-limiting toxicities of the combination at the
      recommended phase II dose of paclitaxel. We also studied the feasibility of
      delivering the paclitaxel as a one-hour infusion at the recommended phase II
      dose. PATIENTS AND METHODS: Thirty-one patients were treated, 25 with stage IV
      disease, and 6 with stage IIIB disease. Ifosfamide was administered at a dose of
      1.6 g/m2 i.v. bolus daily x 3 days, with mesna uroprotection. Paclitaxel was
      administered as a 24-hour infusion at dose levels of 135, 170, 200, 250, and 300
      mg/m2; six patients were treated with a one-hour infusion, at a dose of 250
      mg/m2. G-CSF, 5 micrograms/kg, was administered subcutaneously on days 4 through
      10, or until the absolute neutrophil count exceeded 4000/microliters. Cycles were
      repeated every 21 days. RESULTS: The dose-limiting toxicity was granulocytopenia,
      which increased with increasing dose levels of paclitaxel. The MTD was 300 mg/m2
      of paclitaxel, and the recommended phase II dose 250 mg/m2 administered as a 24
      hour infusion. Other toxicities were generally mild, with only 5 patients
      demonstrating grade 3 neurotoxicity and 5 with grade 3 thrombocytopenia. Partial
      responses were seen in seven patients (23%), all in the 18 patients who received
      dose levels of 250 mg/m2 or higher. CONCLUSIONS: Ifosfamide plus paclitaxel is an
      active treatment regimen in advanced non-small-cell lung cancer, and compares
      favorably with the results of cisplatin-based chemotherapy. A phase II study is
      in progress by the Cancer and Leukemia Group B, in an effort to better
      characterize the tolerance of the regimen, as well as its effect on tumor
      response and survival.

PMID- 8740799
TI  - Prolonged continuous hepatic artery infusion with interleukin-2 in unresectable
      liver metastases of colorectal cancer: a phase IA-B study.

PMID- 8740800
TI  - Combined acute aortic thrombosis and metastatic spinal cord compression causing
      paraplegia in a patient with small-cell lung carcinoma (SCLC)

PMID- 8740801
TI  - Two secondary malignancies following the successful treatment of a patient with
      acute lymphoblastic leukemia.

PMID- 8740802
TI  - Frequency specificity of 80-Hz amplitude-modulation following response.
AB  - The usefulness of 80-Hz amplitude-modulation following response (AMFR) detected
      by phase coherence to predict the hearing threshold during sleep was evaluated in
      90 ears of 53 children with hearing impairment. The threshold of 80-Hz AMFR at
      carrier frequency of 1,000 Hz and the threshold of auditory brainstem response
      (ABR) elicited by 1,000 Hz tone pips in children during sleep were compared with
      behavioral hearing threshold, which was determined by standard pure-tone
      audiometry or play audiometry. In 12 ears of 12 children with various patterns of
      hearing impairment, 80-Hz AMFR at different carrier frequencies were examined,
      and the threshold pattern was compared with the pure-tone audiogram to
      investigate the frequency specificity of 80-Hz AMFR detected by phase coherence.
      The mean and standard deviation of the difference between 80-Hz AMFR and pure
      tone thresholds was 4.3 and 12.1 dB, respectively, and that between ABR and pure
      tone thresholds was 6.6 and 14.2 dB, respectively. The threshold patterns of 80
      Hz AMFR very closely resembled the corresponding audiogram patterns in all types
      of hearing impairment. The measurement of 80-Hz AMFR in children during sleep
      thus appeared to be more accurate in hearing prediction than that by ABR elicited
      with tone pips and to have a good frequency specificity.

PMID- 8740803
TI  - Diagnostic significance of electrocochleogram and auditory evoked brainstem
      response in totally or subtotally deaf patients.
AB  - This paper examined the use of ECoG and ABR in 7 patients with totally or
      subtotally deaf ears. The patients included one with cortical deafness, one with
      psychogenic deafness, one with intrapontine hemorrhage, and 4 with acoustic
      neuroma. In patients with substantial hearing loss, ECoG should be performed
      first if retrocochlear disorders are suspected since results may be obtained even
      in the absence of other auditory evoked potentials. Simultaneous ABR measurements
      can be effective when localizing retrocochlear lesions. ECoG can also help to
      determine the need for preserving hearing during surgery for retrocochlear
      lesions by indicating the degree of cochlear function.

PMID- 8740804
TI  - Abnormal electrocochleography after excision of acoustic neuroma.
AB  - Pre-, per- and post-operative ECoG findings obtained from a 43-year-old woman
      with an acoustic neuroma were studied. Although CAP presented a normal waveform
      in response to click during the whole process of the operation, it was
      transformed into an abnormally broadened negative waveform in shape with a mild
      hearing exacerbation, and has remained unchanged up to the present. This broad
      response was considered to be a receptor potential, because it showed no
      adaptational amplitude reduction. Additionally, postoperative ECoG to tone burst
      stimuli demonstrated an increase in DC potential following the stimulus envelope.
      Consequently, the broad negative response to click was considered to be mainly
      composed of an enlarged negative SP. The generation mechanism underlying the
      phenomenon of an abnormally increased negative SP found after the excision of an
      acoustic neuroma is discussed, with reference to several items in the literature.
      Similar responses in the postoperative ECoG of patients with acoustic neuromas
      obtained by us in the past were given as additional examples. CAP as an indicator
      for intraoperative monitoring can hardly predict postoperative auditory function.
      It is to be hoped that a more reliable auditory monitoring method during the
      operation will be established.

PMID- 8740805
TI  - Acute sensorineural hearing loss caused by Mycoplasma pneumoniae.
AB  - Four cases with acute sensorineural hearing loss on one side and one case with
      bilateral ear fullness associated with Mycoplasma pneumoniae (MP) were described.
      These cases were characterized by highly elevated MP complement fixation titer,
      and cold hemagglutinin titer. All patients experienced cochlear symptoms in an
      early stage following common cold. In all cases, clarythromycin (CAM) had been
      administered for 10 days, and adenosine triphosphate (ATP), vitamin B1, B12, and
      prednisolone were concurrently administered for 14 days. Two cases with acute
      hearing loss and one case with ear fullness returned to normal hearing after
      treatment. The other cases were remarkably improved in hearing level. MP is a
      common causative agent for protein respiratory disease. The true incidence of
      hearing loss in this disease may be higher than has been reported so far. Prompt
      diagnosis possibly facilitates the administration of specific treatment and leads
      to good prognosis.

PMID- 8740806
TI  - Computerized electro-nystagmography.
AB  - A computerized electro-nystagmography (ENG) system was developed on the basis of
      a new idea for the performance of ENG. In this system, all the functions of
      conventional ENG was performed by a personal computer (PC) except for the initial
      setting of an analog amplifier. The eye movement signals from the ENG amplifier
      were displayed on the graphic screen and recorded on a magnetic or magneto
      optical disc. By using a special graphic screen, eye movements, even fine
      nystagmus, can be more clearly observed than they can on the PC's conventional
      graphic screen. Examiners can select the most suitable display condition
      according to the specific purpose(s) of the ENG examination. As a laser printer
      prints the recorded eye movements simultaneously with data sampling, we can
      observe eye movements in the same manner as on the recorded paper of a
      conventional ENG. Moreover, this system has a very powerful function for the
      analysis of such nystagmus responses as caloric test, VOR test and optokinetic
      nystagmus and it can be gotten at a lower cost than conventional ENG. These
      technical and economical features indicate that the computerized ENG system is a
      very useful and convenient device for observing, recording and analyzing ENG
      examinations.

PMID- 8740807
TI  - Clinical significance of step stimulus-induced optokinetic nystagmus.
AB  - The optokinetic nystagmus (OKN) test has diagnostic values in that it can detect
      lesioned sites in patients with infratentorial lesions. The test has so far been
      performed by using angular acceleration to the final velocity over 100 degrees/s,
      which is time-consuming and inconvenient for patients. In the present study, we
      tried to modify and simplify the OKN test used previously to give step stimulus
      of constant stimulus and compared the results in 20 normal subjects. Slow-phase
      velocity versus stimulus velocity, and fast phase amplitude and peak velocity
      versus stimulus velocity of OKN were compared between step-stimulus OKN and
      linear-stimulus OKN. As a result, each parameter showed significantly higher
      values in step-stimulus OKN than in linear-stimulus OKN. Averaged slow-phase OKN
      velocity during the first 5 s is sufficient to calculate OKN velocity, and it
      requires only short time to perform.

PMID- 8740808
TI  - Vertical optokinetic nystagmus in normal individuals.
AB  - In this study, 20 subjects (5 women and 15 men, 22-28 years old) were tested for
      vertical optokinetic nystagmus (OKN) to establish the asymmetry between up and
      down OKN responses in humans. The subjects were exposed to both upward and
      downward OKN stimulus at constant velocities of 30, 40, 50, 60, 70, 80, 90
      degrees/s in the upright position. Eye movements were recorded precisely using
      the magnetic search coil system in order to eliminate any methodological problem
      associated with the eye-lid artifact. Slow phase velocity during upward OKN
      stimulus was higher than that during downward OKN stimulus for each OKN velocity.
      It is likely that otolithic stimuli cause up and down asymmetry. Statistical
      significance in the gain between upward and downward OKN was noted for stimulus
      velocities of 30-60 degrees/s (p < 0.01), but not for higher velocities, because
      vertical OKN saturated around 40-50 degrees/s.

PMID- 8740809
TI  - Primary position upbeat nystagmus with special reference to alteration to
      downbeat nystagmus.
AB  - A 24-year-old man was admitted to the University Hospital showing severe
      dehydration that might have been the result of medicine-induced gastritis.
      Wernicke's encephalopathy was suspected in this patient. On admission, primary
      position upbeat nystagmus (PPUN) was found. The patient showed tongue
      fasciculation and loss of gag reflex, which, however, soon returned to normal.
      Electronystagmographic (ENG) findings were suggestive of lesions in the
      brainstem. Based on neurological signs and symptoms, we concluded caudal
      brainstem lesions might be a possible site responsible for the upbeat nystagmus.
      This nystagmus, however, was later found to be reversed to downbeat nystagmus.
      This is considered to have been due to predominant differences in vertical
      velocity which are induced by gravity.

PMID- 8740810
TI  - Alternations of eye movements induced by visual stimulation in a patient with
      acute cerebellar infarction.
AB  - We had the opportunity to investigate a patient with acute cerebellar infarction
      with edema that extended to the brainstem, using CT-scan and electrooculography
      (EOG). The purpose of this paper was to analyze the pursuit eye movements,
      saccades, optokinetic nystagmus (OKN) and fixation-suppression of the caloric
      test in an acute cerebellar infarction and on CT-scans to evaluate the
      connections between eye movements and lesions in the vestibulocerebellum. At the
      onset of infarction, data of the eye movements suggested that the lesioned area
      involved the bilateral dorsal pontine tegmentum and bilateral cerebellum,
      although the left side was predominantly impaired, as judged from the CT-scans.
      After more than 3 weeks from onset, deviation of the fourth ventricle and
      compression to the brainstem due to edema were not observed. Nevertheless, the
      parameters of conjugate eye movements that were analyzed had not recovered
      completely. This suggests that impairment of a neural integrator may still exist.

PMID- 8740811
TI  - Role of the neuronal activity of nucleus prepositus hypoglossi in optokinetic
      stimulation in the cat.
AB  - The role of the neuronal activity of nucleus prepositus hypoglossi (NPH) in
      optokinetic stimulation (OKS) and the changes of the activity between OKS and off
      OKS (resting condition) were investigated in 5 adult cats. In order to make OKS
      velocity equal to retinal slip velocity, the cats' eyes were immobilized. The
      directions of the OKS were clockwise (CW) and counterclockwise (CCW), and 3 types
      of velocities, 2 degrees/s, 5 degrees/s and 10 degrees/s, were used. The numbers
      of spikes of 37 NPH neurons to OKS did not increase compared with those to off
      OKS, also there were no significant differences between those to CW-OKS and CCW
      OKS, and between those of the rostral and caudal parts of NPH. The NPH neurons
      did not react to the retinal slip, and we suppose the result is due to the
      immobilized eye condition.

PMID- 8740812
TI  - Autoradiographic evidence of steroid affinity sites in nasal tissue.
AB  - Affinity sites of glucocorticoid (GC) in nasal tissue were investigated using
      radiolabelled synthetic GC. The affinity sites of GC are epithelium, vein,
      leukocyte and gland. The tracer was retained in the cytoplasma but not in the
      nuclei in most parts of the nasal tissue except for the endothelial cells of the
      vein. Therefore we assume that there is a direct mechanism of steroid action on
      nasal tissue suffering from allergic rhinitics other than the so-called steroid
      receptor complex. Affinity sites of corticosterone (CS) in nasal tissue were
      investigated using radiolabelled CS. The differences of affinity sites of GC and
      mineralcorticoid in unsensitized rats were evaluated, but no major differences
      between them could be confirmed.

PMID- 8740813
TI  - Serum levels of RIST, RAST, and cortisol of patients with allergic rhinitis.
AB  - It is generally known that in Type 1 allergy, adrenal steroid hormonesregulate
      the production of IgE antibody. This study was carried out to determine whether
      patients with rhinitic allergy to Japanese cedar pollencan modulate the
      interaction between the immune and endocrine systems normally. The subjects were
      61 patients allergic to Japanese cedar pollen, and 14 healthy volunteers served
      as control. Our study suggests that downregulation of the HPA axis may be caused
      by high specific and non-specific IgE production in patients with allergic
      rhinitis, Our data suggest that cortisol may play a role as an immuno-suppressive
      agent in specific IgE production during the pollen season, as this phenomenon was
      not observed before or after the pollen season.

PMID- 8740814
TI  - Pollinosis etiologic relationship between excessive IL-4 production and down
      regulation of the inflammation-suppressive system.
AB  - Previous findings suggest a bi-directional relationship between the immune and
      endocrine systems, which may expand to a major inflammation-regulatory mechanism,
      although its mechanism is largely unknown, especially in the human body.
      Lymphokine and neuroendocrine peptide hormones have been identified as two major
      groups of immunologic mediators. The particularly pivotal molecules among them
      are interleukin (IL-1), considered to be a mediator of inflammation, and ACTH,
      whose activation is induced by IL-1. Among the important functions of lymphokines
      related to atopic inflammation is the regulation of IgE secretion from B cell
      through the action of IL-4, produced from the Th2 subset stimulated by IL-1, as a
      switch factor. IL-4 is the major IgE secretagogue. IL-4 is, moreover, a potent
      suppressive stimulant of IL-1 secretion. In this study, we tested the hypothesis
      whether a immunologic interaction exists in patients with allergic rhinitis to
      Japanese cedar pollen. We performed immunohistochemical staining of IL-1 beta,
      interleukin 1 receptor (IL-1r) and interleukin-4 (IL-4) in the nasal tissue, and
      evaluated serum levels of the biochemical mediators involved in the inflammation
      regulatory mechanism: IL-1 beta, IL-4, interleukin 1 receptor antagonist (IL
      1ra), IgE, cortisol, and ACTH before, during, and after allergen-provoked
      rhinitis in pollinosis sufferers. Our morphological study showed that, even
      before the pollen season, large amounts of IL-4 and IL-1r, exclusive of IL-1
      beta, were produced in the nasal tissue of patients with seasonal pollinosis. IL
      1-positive cells were observed in small amounts in the same tissue, but the
      quantity was probably enough to cause secretion of intrinsic IL-4 to produce
      sufficient IgE for atopic inflammation. Upon immunoenzymatic measurement of serum
      IL-4, even before the pollen season, almost all atopic patients also showed a
      higher IL-4 level than controls. Serum IgE data also showed a high level before
      the pollen season in atopic patients. This evidence suggests that atopic patients
      have already set the first step of inflammatory event not only in the nasal
      epithelium but also generally even before inhaling proper quantity and quality of
      the allergen. On the other hand, although atopic patients had inflammation, they
      did not show an extremely high value of serum IL-1, regarded as inflammatory
      lymphokine, compared with non-atopic individuals. In contrast, a higher serum
      level of IL-1ra was observed before and during the pollen season in atopic
      patients, subsiding to normal level after the season. Serum levels of both
      cortisol and ACTH did not show a high value in atopic patients during the season.
      These results demonstrate that excessive IL-4 production of atopic patient causes
      down-regulated transformation of IL-1 and up-regulated secretion of IL-1ra
      generally, followed by failure to increase secretion of ACTH from hypophysis and
      cortisol generally, resulting in defective performance of a specifically useful
      function of the anti-inflammatory mechanism.

PMID- 8740815
TI  - Immunohistochemical observations of antigen presenting cells and follicular
      dendritic cells in the tonsil.
AB  - In the present study, in order to investigate the behavior in the lymphatic
      system of phagocytic cells which incorporate potential antigen in the tonsile
      crypt, the distribution of HRP stained macrophages in the tonsillar system was
      observed with regard to changes with time. Furthermore, in the tonsillar tissue,
      in order to investigate the relationship among HRP marked macrophages, follicular
      dendritic cells and adhesion molecules, such as ICAM-1, immunological double
      staining was performed. It is open to discussion whether ICAM-1 plays an
      important role as an adhesive molecule in this migration of macrophages.
      Immunohistochemical double staining method detected a relation between anti-ICAM
      1 antibody positive cells and antigen stained macrophages. In the stained area
      between anti-ICAM-1 antibodies and anti-DRC-1 antibodies, positive cells were
      clearly observed to have reticular form, particularly in the mature germinal
      center. This phenomenon implies that dendritic cells express ICAM-1 on the cell
      surface to contact other immunorelated cells and/or substances. In the inter
      follicular space, anti-ICAM-1 antibody positive cells were observed to form a
      cluster composed of ICAM-1 positive cells, lymphocytes and HRP stained
      macrophages. This cluster may be considered the most primary stage of follicles
      or as triggering the creation of an inmature follicle.

PMID- 8740816
TI  - Antibodies of type II collagen and immune complexes in Meniere's disease.
AB  - In a previous study, we showed that endolymphatic hydrops was induced in 36% of
      guinea pigs immunized with type II collagen and that dominant negative summating
      potential (SP) was recorded for these hydropic animals. In the present study, we
      evaluated the levels of serum antibody to type II collagen and three other immune
      indexes in patients with Meniere's disease, especially those who showed negative
      SP dominance in ECoG. Twenty-nine Meniere's cases, 22 normal volunteers serving
      as controls, 28 rheumatoid arthritis (RA) cases, and 9 patients complaining of
      vertigo were examined to detect serum immune indexes. Meniere's patients
      exhibited high values of serum anti-type II collagen antibody compared with
      control subjects. Furthermore, total IgG, C3, anti-type II collagen antibody and
      CIC were increased with the highest levels being in the RA group, followed by
      Meniere's disease group and then the control group. These results probably
      reflect the extent of immune reaction development. The immune response may be
      generalized in RA cases and/or local in Meniere's disease. These results suggest
      the development of certain immune status abnormalities in our cases, which lends
      support to the idea of immunologic disorder playing a role in the etiology of
      some cases of Meniere's disease.

PMID- 8740817
TI  - Localization of Epstein-Barr virus in lymph node metastasis with nasopharyngeal
      carcinoma.
AB  - Epstein-Barr virus DNA was detected in 3 cases of lymph node metastasis with
      nasopharyngeal carcinoma, using in situ hybridization. EBV-DNA was demonstrated
      on the nuclei of the neoplastic cells, and was absent on those of lymphocytes.
      Localization of EBV-DNA in neoplastic cells was confirmed by the double-labeling
      method combining in situ hybridization and immunocytochemistry. Direct evidence
      of the presence of EBV-DNA in malignant epithelial cells from lymph node
      metastasis with nasopharyngeal carcinoma was clearly demonstrated in this study.

PMID- 8740818
TI  - An experimental model of multistep laryngeal carcinogenesis: combined effect of
      human papillomavirus type 16 genome and N-methyl-N'-nitro-N-nitrosoguanidine.
AB  - This report describes the two-step in vitro transformation of human laryngeal
      epithelial cells (HLEC cells). Primary cultured HLEC cells were first transfected
      with cloned full-length human papillomavirus type 16 DNA, and two immortalized
      cell lines (HLEC-16 cell lines) were selected by subculturing transfected cells
      that continued to proliferate. The HLEC-16 cell lines were not tumorigenic in
      nude mice, and did not proliferate well in a culture medium containing a
      physiological level of calcium (Dullbecco's minimum essential medium supplemented
      with 10% fetal bovine serum = DMEM + 10%FBS). The HLEC-16 cell lines were
      secondarily exposed to N-methyl-N'-nitro-N-nitrosoguanidine, and several
      proliferating colonies were isolated in DMEM + 10%FBS. Among these calcium/serum
      resistant cell colonies, one colony exhibited enhanced proliferation capacity in
      nude mice. These results support the hypothesis that human laryngeal epithelial
      cells may be the target for neoplastic transformation by a combined effect of
      human papillomaviruses and chemical carcinogens.

PMID- 8740819
TI  - Spontaneous mutation of p53 gene in human papillomavirus type 16 E7-immortalized
      human laryngeal epithelial cells.
AB  - The E7 gene is one of the principle transforming genes of human papillomavirus
      type 16 (HPV 16). In this study, we show that HPV 16 E7 gene could immortalize in
      vitro primary human laryngeal epithelial cells (HLEC cells) without cooperation
      of the viral E6 gene. The HPV 16 E7-immortalized HLEC cell line had acquired a
      mutation of a tumor suppressor gene, p53, during the immortalization process.
      Using immunofluorescence assay, nuclear accumulation of p53 protein was found in
      the cell line. These results suggest that HLEC cells can be immortalized in vitro
      by the cooperative activities of HPV 16 E7 gene and a spontaneous mutation of the
      endogenous p53 gene.

PMID- 8740820
TI  - Atypical osteomyelitis of the temporal bone.
AB  - Osteomyelitis of the temporal bone is a rare disease. The diagnosis and treatment
      of atypical osteomyelitis of the temporal bone in a 54-year-old woman was
      reported. The left temporal bone swelling grew slowly from age 9 with only slight
      deep-seated pain in the temporal area. This condition was assumed to be due to
      fibrous dysplasia or some benign tumor. It is supposed that exploratory and
      inadequate mastoidectomies performed on patients age 16 to 19 years might trigger
      temporal bone osteomyelitis. Extensive surgical debridement followed by
      antibiotic therapy for 4 weeks yielded good results, and now 2 years after
      treatment, no signs of recurrence have been observed. The utility of the gallium
      scan was confirmed for evaluation of disease activity.

PMID- 8740821
TI  - Two unusual cases of a foreign body in the oral cavity caused by eating raw
      squid.
AB  - Foreign bodies are often encountered by otolaryngologists, but the oral cavity is
      considered a place where foreign bodies are rare because of its structural and
      functional features. We here present 2 cases with a foreign body in the oral
      cavity resulting from eating raw squid. In one of these 2 cases endoscopic
      examination revealed a gastric foreign body. The foreign bodies in the oral
      cavity were removed using forceps, together with surrounding mucous membrane.
      These foreign bodies were identified as sperm bulbs and discharging tube of
      sogittated calamary (Todarodes pacificus Steenstrup). Larva migrans of
      anisakiasis are to be differentiated from sperm bulbs; it is important to
      distinguish between the shape and size of the foreign body in our cases. If sperm
      bulbs are stuck in the oral cavity, it is necessary to remove them completely to
      ensure that inflammation is prevented. We stress the importance of checking not
      only anisakiasis but also sperm bulbs in humans who like eating raw squid.

PMID- 8740822
TI  - Effects of administration of high dose hydrocortisone on Bell's palsy.
AB  - As an improved maintenance therapy for Bell's palsy, Stennert recently introduced
      large-dose steroid administration in the early stage of the disease with i.v.
      infusion of low-molecular dextran. The steroid administration aims at improving
      the microcirculation. This therapy achieved a 96% complete healing rate. However,
      because of side-effects such as hepatic and renal disorders or gastric ulcer,
      this therapy has not been widely used. In the present study, we investigated an
      improved treatment method based on Stennert's method. It has a much lower
      incidence of side effects, and can be used in routine clinical practice. The
      medicines employed in our therapy were hydrocortisone sodium succinate (Solu
      cortef), hydroxymethylated starch (Hespander) and D-mannitol (Manitol). Subjects
      were 53 Bell's palsy patients for whom treatment could be started within 2 weeks
      from the onset of the disease. Curative rate in the patients who received large
      dose administration of Solu-cortef was 96.2% in the 24th week, and the therapy
      was considered to be applicable in routine clinical practice for Bell's palsy.

PMID- 8740823
TI  - A case report of acquired choanal atresia.
AB  - A case of acquired choanal atresia of unknown origin is reported. A 68-year-old
      woman had been complaining of nasal obstruction for 28 years. Bilaterally her
      nasal choanae were found to be completely closed at the depth of the orifice of
      the eustachian tube. Surgical intervention into the margin of the soft and hard
      palate removed the adhesive connective tissue from the choanae, which had
      involved no osseous component. Because part of the intranasal basal epithelium
      was missing due to surgery, buccal mucosa was removed and implanted to prevent
      proliferation of granulation. A silicone tube was placed in each choanae for a
      week postoperatively. An adequate nasal passage has been maintained for 10 months
      postoperatively, and the patient was followed up closely.

PMID- 8740824
TI  - Surgical treatment for caustic ingestion injury of the pharynx, larynx, and
      esophagus.
AB  - A 45-year-old female drank Sunpole (9.5% hydrochloric acid), an acidic toilet
      cleaner, in a suicide attempt. Notwithstanding intravenous administration of
      steroids and bougienage dilation, corrosive changes progressed. The patient
      underwent surgery for severe caustic ingestion injury of the pharynx, larynx, and
      esophagus. Colon bypass surgery from the left vallecula to the stomach was
      performed. Excellent results, both in deglutition and phonation, were obtained.
      We report on the case and stress several points of importance in dealing with
      severe caustic ingestion injuries.

PMID- 8740825
TI  - US-guided drainage of deep neck space abscess.
AB  - Infection of oropharyngeal or upper airway origin may extend to potential spaces
      formed by fascial planes of the cervical area. These space infections have been
      greatly reduced by modern antibiotic therapy. However, serious complications
      continue to occur. An 18-year-old man who presented with neck mass was admitted
      and treated. He underwent ultrasonically guided drainage procedure using
      Percuflex drainage catheter within 6 h of his arrival. He was discharged from the
      hospital 10 days later. Although it is still thought that early open surgical
      drainage is the most appropriate method for treatment of deep cervical abscess,
      early treatment with a drainage catheter such as Percuflex may replace surgery.
      Life threatening complications can thus be avoided with good cosmetic results and
      rapid recovery.

PMID- 8740826
TI  - Effectiveness of formula ophiopogoins in the treatment of xerostomia and
      pharyngoxerosis.
AB  - A multicenter study was carried out in 24 institutions in Kanagawa Prefecture,
      Japan. The subjects were 113 male and 145 female patients, ranging in age from 28
      to 86 years (mean 63.7) who complained of dryness of the mouth and throat. The
      following illnesses were diagnosed: xerostomia and pharyngoxerosis in 161,
      radiation xerostomia and pharyngoxerosis in 56, chronic pharyngitis with dry
      mouth and throat in 22, and Sjogren's syndrome in 7. Eleven patients had other
      symptoms. The subjects were given a 3-g pack of granules of formula ophiopogoins
      three times a day before a meal. Their subjective symptoms and objective signs
      were examined prior to, 2, and 4 weeks after the beginning of therapy.

PMID- 8740827
TI  - Three cases of eosinophilic lymphfolliculoid granuloma of the soft tissue
      originating from the parotid gland.
AB  - Two women aged 33 and 57 years respectively, and a man aged 40 years visited our
      hospital complaining of swelling of the parotid gland region. The diagnosis of
      eosinophilic lymphfolliculoid granuloma of the soft tissue (Kimura's disease)
      based on laboratory findings was made in all 3 cases. Patient 1 received
      radiation therapy followed by surgery, and Patients 2 and 3 were treated with
      antiallergics and antiinflammatory agents after surgery. Satisfactory results
      were obtained in all cases. Although Kimura's disease is a benign tumor, no
      established therapy is available so far, and a high recurrence rate is the major
      concern. Based on our experience and treatments reported in the literature, we
      conclude that a combination therapy consisting mainly of surgery is the most
      effective treatment of Kimura's disease.

PMID- 8740828
TI  - Transcutaneous intracordal silicon injection for unilateral vocal cord paralysis.
AB  - Unilateral recurrent laryngeal nerve paralysis causes the vocal cord to atrophy,
      leading to glottic incompetence. The voice is characterized by hoarseness,
      breathlessness, rapid air escape, ineffective cough and aspiration. Traditional
      treatments of unilateral vocal cord paralysis include intracordal injection,
      laryngeal framework surgery, and laryngeal reinnervation for medialization of the
      vocal cord. In this paper we report on a new technique of transcutaneous
      intracordal silicon injection in which the injection is made through the thyroid
      lamina under local anesthesia monitoring fiberscopy. We performed this procedure
      on 30 patients with unilateral vocal cord paralysis and later evaluated their
      post-operative voice. The silicon injection resulted in improvement of vocal
      quality, favorable clearance of sputum, and aspiration control. We found that,
      since it can be performed under local anesthesia without hospitalization,
      transcutaneous intracordal silicon injection should be performed as a therapy for
      treating unilateral vocal cord paralysis.

PMID- 8740829
TI  - Two cases of esophageal diverticula.
AB  - Two cases of pharyngoesophageal diverticula were reported with reference to
      previous studies. Definite diagnosis was established by esophagography. The
      surgical treatment is generally conducted in accordance with Goodman-Parnes'
      criteria for surgical indication. We also carried out surgery on the basis of
      this criteria. One-stage diverticulectomy was performed and favorable results
      with no postoperative complications were obtained.

PMID- 8740830
TI  - Two cases with glossopharyngeal neuralgia treated by nerve reaction:
      oropharyngeal approach.
AB  - Two patients with idiopathic glossopharyngeal neuralgia received glossopharyngeal
      nerve resection by the oropharyngeal method, and their symptoms were relieved.
      Both patients had suffered proxysms of severe pain in the unilateral
      glossopharyngeal innervation for many years, and pharmaceutical treatment had
      been made in vain and, although surgical intervention in one patient had resulted
      in temporary relief, it had not been possible to prevent recurrence. As the
      identification of trigger zones by the method of local nerve block caused us to
      think that surgical treatment would be more effective in both patients, the
      glossopharyngeal nerve was resected, using the oropharyngeal method, with a view
      to attaining permanent symptomatic relief. Consequently, satisfactory results
      were obtained.

PMID- 8740831
TI  - Wavelet analysis of DNA sequences.
AB  - Wavelet decomposition is applied to the analysis of the nucleotide sequence of
      the rhodopsin gene of Chinese Hamster cells. The Lipschitz-Holder exponents for
      the probability measurements of adenine, guanine, thymine and cytosine
      distributions are obtained. The local scaling found by means of wavelet analysis
      is argued to be an indication of long-range correlations.

PMID- 8740832
TI  - Protein folding: from basic science to biotechnology.

PMID- 8740833
TI  - A nonradioactive method for improved restriction analysis and fingerprinting of
      large P1 artificial chromosome clones.
AB  - The P1 artificial chromosome (PAC) cloning system is very useful for physical
      mapping, however, the large insert sizes cause difficulty in routine restriction
      analysis. In order to facilitate restriction mapping and fingerprinting, we have
      developed a simple, nonradioactive method for end-labeling and detection of
      restriction fragments from PAC clones. This method is very easy to implement,
      gives good differentiation of restriction fragments, and uses comparatively small
      amounts of DNA. We have used this method for restriction analysis of PAC clones
      containing inserts from human as well as from lower vertebrates. The method
      should also be applicable to other large-insert plasmid systems.

PMID- 8740834
TI  - Fiber-FISH: experiences and a refined protocol.
AB  - One of the most time-consuming steps in positional cloning is the physical
      mapping of probes from the critical chromosomal region and the assembly of a
      genomic contig of large insert probes. New high-resolution Fiber-FISH techniques
      have significantly facilitated this tedious task by enabling rapid direct
      visualization of the order, degree of overlap and gap sizes of adjacent large
      insert clones. We have developed a method, where agarose-embedded DNA (PFGE
      block) is used as a source for preparing linearized DNA targets on microscope
      slides. This modification of the fiber-FISH technique has been successfully used
      in physical mapping in the 1-300 kb range as well as for detecting genomic
      rearrangements. Here, we present a refined protocol of our original technique.
      The application of this technique to agarose embedded yeast cells is also
      demonstrated. Finally, critical steps and trouble shooting of the method are
      addressed.

PMID- 8740836
TI  - Using electroporation and a slot cuvette to deliver plasmid DNA to insect
      embryos.
AB  - Microinjection is the method used almost exclusively to deliver DNA constructs to
      insect embryos while electroporation is commonly used for DNA delivery to
      bacteria, cell cultures and certain plant tissues. This communication describes a
      method using an easily constructed slot cuvette and the electroporation technique
      for transfer of DNA to insect embryos for possible use in developing methods for
      germline transformation. This method eliminates time-consuming individual embryo
      manipulation and thus far has been found to be adaptable for use on several types
      of insect embryos. Using this method, we show successful transfer of plasmid DNA
      to embryos of the corn earworm moth, Helicoverpa zea, and the house fly, Musca
      domestica.

PMID- 8740835
TI  - Thermostable Bst DNA polymerase I lacks a 3'-->5' proofreading exonuclease
      activity.
AB  - A thermostable DNA polymerase, the Bst DNA polymerase I, from Bacillus
      stearothermophilus N3468 was prepared to near-homogeneity. The dominant species
      of the Bst DNA polymerase I preparation sized about 97 kDa when analyzed on SDS
      polyacrylamide gels. The Bst polA gene that codes for Bst polymerase I was cloned
      and sequenced. Comparative sequence analysis showed that all three conserved 3'-
      >5' exonuclease motifs found in E. coli DNA polymerase I were missing in Bst DNA
      polymerase I. This cast doubt on the existence of a 3'-->5' exonuclease function
      in that enzyme. Four biochemical assays were used to measure exonuclease
      activities of Bst DNA polymerase I, testing both full-length Bst polymerase I and
      the Bst large fragment which lacks the N-terminal 5'-->3' exonuclease domain.
      These exonuclease assays demonstrated that Bst DNA polymerase I only contained a
      double-strand dependent 5'-->3' exonuclease activity but lacked any detectable 3'
      ->5' proofreading exonuclease activity. The lack of 3'-->5' exonuclease function
      in a variety of thermostable repair DNA polymerases may reflect enhancement of
      thermostability at the expense of proofreading activity.

PMID- 8740837
TI  - Rapid detection of common Chinese glucose-6-phosphate dehydrogenase (G6PD)
      mutations by denaturing gradient gel electrophoresis (DGGE).
AB  - We describe here the use of denaturing gradient gel electrophoresis (DGGE) to
      detect the most common Chinese glucose-6-phosphate dehydrogenase (G6PD) variants,
      which are the single point mutations: G-->T at nt 1376, G-->A at 1388 both in
      exon 12 and A-->G at nt 95 in exon 02. In each case, the mutant allele resolves
      well from the normal allele(s). The distinct heteroduplex bands are
      characteristic of a particular genotype suggesting that this feature is very
      useful for identifying all heterozygous carriers for this and other X-linked
      diseases. When the analysis is extended to other exons, DGGE scans the gene and
      coupled with direct sequencing, it leads to the identification of new G6PD
      variation(s). With this approach, we identified a mutation in exon 9 which had
      not been reported in Hong Kong. Since DGGE can rapidly screen many unknown
      samples in one gel, this approach could be used to diagnose these G6PD mutations
      and to identify the at-risk for counselling.

PMID- 8740838
TI  - Liver tumors and possible preneoplastic lesions, induced by a food-derived
      heterocyclic amine in cynomolgus monkeys; a study of histology and cytokeratin
      expression.
AB  - A food-derived mutagenic heterocyclic aromatic amine, 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ), is a potent hepatocarcinogen in cynomolgus monkeys. In an
      ongoing carcinogenesis study, 34 out of 40 monkeys dosed with IQ have developed
      malignant liver tumors. The histology and cytokeratin expression was examined in
      a total of 94 tumors and non-neoplastic lesions obtained from 34 cases. The
      majority of the tumors were classified as hepatocellular carcinoma. In some
      cases, a striking difference in the histological features between individual
      tumor nodules was suggestive of a multicentric origin. Intrahepatic vascular
      invasion was seen in 14 (41.2%) and metastases in 6 (17.6%) of the hepatocellular
      carcinoma cases. There was no evidence of regenerative hyperplasia or fibrosis in
      the parenchyma of the tumor-bearing livers. Clear-cell foci composed of glycogen
      rich hepatocytes were the only macroscopic lesions detected prior to gross tumor
      development. Other liver lesions included dysplastic hepatocyte foci and areas of
      proliferating bile ductular like (oval) cells, located around the periportal
      areas and along the portal tracts. Expression of bile duct type cytokeratin 7 was
      observed in a few of the oval cells and non-malignant hepatocytes, as well as in
      some of the hepatocellular carcinoma nodules. This aberrant cytokeratin
      expression raises questions concerning the histogenesis of the IQ-induced
      hepatocellular carcinoma.

PMID- 8740839
TI  - Does the measurement of portal flow velocity have any value in the identification
      of patients with cirrhosis at risk of digestive bleeding?
AB  - Upper gastrointestinal bleeding is a leading cause of death in patients with
      liver cirrhosis. In most cases haemorrhage originates from oesophageal varices or
      from congestive gastropathy, and the evaluation of the bleeding risk is based on
      oesophagogastroduodenoscopic data. The aim of this prospective study was to
      determine whether the measurement of portal flow velocity by Duplex-Doppler,
      compared with endoscopic data, can help in detecting patients with cirrhosis at
      risk of bleeding. One hundred and seventy-three patients underwent endoscopy to
      ascertain the size of the varices and the severity of congestive gastropathy. For
      each patient maximal portal flow velocity measurements were obtained. No
      difference in portal flow velocity was observed between patients with or without
      oesophageal varices or congestive gastropathy. During a 2-year observation
      period, 27 patients (15.6%) had at least one episode of acute digestive bleeding.
      Stepwise multiple logistic regression analysis demonstrated a correlation between
      oesophageal varices and congestive gastropathy endoscopic grading and the
      incidence of bleeding; only the former was entered into the final regression
      equation (p < 0.001). No relationship between the max portal flow velocity value
      and incidence of bleeding was found. This study shows that portal flow velocity
      is unrelated to the degree of the endoscopic abnormalities in patients with liver
      cirrhosis and that it has no value in the identification of patients with
      cirrhosis at risk of upper gastrointestinal bleeding.

PMID- 8740840
TI  - Treatment of woodchuck hepatitis virus infection in vivo with 2', -3'
      dideoxycytidine (ddC) and 2',-3'-dideoxycytidine monophosphate coupled to
      lactosaminated human serum albumin (L-HSA ddCMP).
AB  - Dideoxycytidine (ddC) is a nucleoside analogue active against human
      immunodeficiency virus and with in vitro activity against human hepatitis B
      virus. We investigated the ability of ddC to inhibit one of the Hepadnaviridae,
      the woodchuck hepatitis virus and compared the results with the effect obtained
      by a conjugate of lactosaminated human serum albumin 2',-3'-dideoxycytidine
      monophosphate (L-HSA ddCMP). This compound specifically enters the hepatocyte via
      the asialoglycoprotein receptor. We treated five chronic woodchuck hepatitis
      virus carriers with intravenous injections of 0.5 mg/kg body weight of ddC for 5
      consecutive days, and under the same protocol five woodchucks with 10.4 mg/ kg L
      HSA ddCMP, a dose equivalent to 0.25 mg/kg of free ddC. A reduction of serum
      woodchuck hepatitis virus DNA (5-125 fold) was observed during therapy in three
      out of five animals receiving ddC and in two of the five animals treated with L
      HSA ddCMP. In responding woodchucks, virus DNA levels rebounded immediately after
      stopping therapy. No signs of toxicity were observed during or after the course
      of therapy. These preliminary results of short-term treatment indicate that ddC
      has anti-viral activity against woodchuck hepatitis virus. When the dose was
      reduced by 50%, L-HSA ddCMP showed anti-viral activity to an even lesser degree.

PMID- 8740841
TI  - Portal vein thrombosis complicating hepatocellular carcinoma. Value of ultrasound
      guided fine-needle biopsy of the thrombus in the therapeutic management.
AB  - During a 4-year period portal vein thrombosis was diagnosed in 20 Child class A
      patients with cirrhosis by means of ultrasound and ultrasound-Doppler study.
      Seventeen of them showed single or multiple focal liver lesions diagnosed as
      hepatocellular carcinoma by ultrasound-guided fine-needle biopsy and the
      remaining three a coarse liver echo-pattern without focal lesions. One patient
      was found to have developed portal vein thrombosis after the fifth ethanol
      injection of a single hepatocellular carcinoma lesion 17 mm in diameter.
      Ultrasound-guided fine-needle biopsy of the thrombus was performed on all the
      patients: portal vein thrombosis was neoplastic in 13 cases and non-neoplastic in
      seven cases (five patients with a single lesion; one with two lesions; one with
      coarse liver echo-pattern). Among the five patients with a single lesion, one had
      already been treated by percutaneous ethanol injection therapy. There were no
      complications related to the biopsy procedures. The diagnosis of non-neoplastic
      thrombosis allowed five new patients to be recruited for percutaneous ethanol
      injection treatment and allowed it to continue in the patient with portal vein
      thrombosis occurring after the fifth ethanol injection. The routine use of
      ultrasound-guided fine-needle biopsy of portal vein thrombosis yields an accurate
      diagnosis of the nature of the thrombus and can improve the selection for
      percutaneous ethanol injection treatment of patients with cirrhosis with
      hepatocellular carcinoma lesions.

PMID- 8740842
TI  - Expression of p53 in adenocarcinoma of the gallbladder and bile ducts.
AB  - Point mutation of the p53 tumor suppressor gene appears to be an important event
      in tumor development and progression, and overexpression of the p53 gene product
      has been widely studied in a variety of neoplasms. Some point mutations of the
      p53 gene lead to an increase in half-life in the gene product, which accumulates
      in the nucleus and can be detected by immunohistochemical means. We studied
      overexpression of p53 protein in specimens from 12 patients with adenocarcinoma
      of the gallbladder, two gallbladders with epithelial dysplasia without carcinoma,
      eight carcinomas of the common bile duct, 13 hilar cholangiocarcinomas, and six
      peripheral cholangiocarcinomas. The monoclonal antibody Ab-2 (Oncogene Science)
      was used in conjunction with citrate microwave antigen retrieval. Nuclear
      staining was scored as positive (graded 1 to 3, depending on number of positive
      nuclei) or negative. Overexpression of p53 protein was present in 7/12 (58%)
      gallbladder carcinomas, and was seen more often in moderately or poorly
      differentiated tumors. Intramucosal carcinoma adjacent to invasive carcinoma was
      positive in three cases, although fewer cells stained than in the carcinoma. Two
      cases of low-grade dysplasia not associated with carcinoma were negative.
      Expression of p53 was not an independent prognostic factor when survival was
      related to grade and stage of tumor. Three of eight (38%) common bile duct
      carcinomas and 5/13 (38%) hilar cholangiocarcinomas were positive for p53.
      Slightly fewer (2/6, 33%) peripheral cholangiocarcinomas were positive. No
      difference in survival relative to p53 expression was demonstrated.

PMID- 8740843
TI  - Do serum ALAT values reflect the inflammatory activity in the liver of patients
      with chronic viral hepatitis?
AB  - A retrospective study was carried out in 40 patients with chronic viral
      hepatitis, to assess whether serum alanine aminotransferase reflects the
      inflammatory process in the liver. Twenty liver biopsy specimens were included
      for each disease. Five histological aspects were scored: periportal inflammation,
      lobular inflammation, ballooning, Councilman bodies and lymphocyte follicles.
      Logarithmic values of alanine aminotransferase were correlated with each aspect
      using the Spearman correlation coefficient. For the hepatitis B cohort a
      statistical significant correlation was found between alanine aminotransferase
      and periportal inflammation (p = 0.0001), lobular inflammation (p = 0.0002) and
      Councilman bodies/area (p = 0.003). In the hepatitis C study population alanine
      aminotransferase correlates with both periportal inflammation (p = 0.007) and
      lymphocyte follicles/Area (p = 0.02). In conclusion, these results suggest that
      alanine aminotransferase can be used as an indicator of inflammatory activity. A
      prospective study is needed, to further analyze the use of alanine
      aminotransferase, as a monitor of disease activity in patients with chronic viral
      hepatitis.

PMID- 8740844
TI  - Seroprevalence of HBV (anti-HBc, HBsAg and anti-HBs) and HDV infections among
      9006 women at delivery.
AB  - Serum samples from 9006 women, who delivered in Switzerland in 1990 and 1991,
      were collected around the country. Of these women, 62.7% were Swiss and 37.3%
      originated from foreign countries. Samples were first screened for anti-HBc and
      those found positive were further tested for HBsAg, anti-HBs and anti-HDV. Anti
      HBc was found in 640 of the 9006 women (overall prevalence, 7.1%; Swiss, 3.3%;
      foreigners, 13.5%). Of these 640 positive samples, 61 (9.5%) were positive for
      HBsAg (without anti-HBs), 467 (73.0%) positive for anti-HBs (without HBsAg) and 8
      (1.3%) positive for both HBsAg and anti-HBs. The remaining 104 were thus anti-HBc
      positive without HBsAg or anti-HBs. These 104 specimens with the so-called
      "isolated anti-HBc" reactivity represented 1.2% of the whole population or 16.3%
      of the 640 anti-HBc positive mothers. All were HBV DNA negative (PCR). Anti-HDV
      antibody was found in only five women. HBsAg was seen in 38 of the cord-blood
      samples from the anti-HBc positive mothers. In this large sampling, we observed a
      relatively high seroprevalence of HBV infection. Cases with isolated anti-HBc
      reactivity, being HBV DNA negative by PCR, were probably non-infectious at the
      time of blood collection.

PMID- 8740845
TI  - Risk of HBV reinfection after liver transplantation in HBsAg-positive cirrhosis.
      Primary hepatocellular carcinoma is not a predictor for HBV recurrence. The
      European Cooperative Study Group on Liver Cancer and Transplantation.
AB  - Two hundred and twenty-eight patients who underwent orthotopic liver
      transplantation for hepatitis B-related cirrhosis in 11 European Liver Transplant
      Centers were collected. The male/female ratio was 184/44, with a median age of 41
      years (13-66). In 55 patients (24%) hepatocellular carcinoma was associated with
      liver disease. All cases were stratified for pre-orthotopic liver transplantation
      viral characteristics: HBV-DNA neg/HBeAg neg: 106 patients (47%), HBV-DNA
      neg/Delta pos: 80 (35.5%), HBV-DNA pos/HBeAg pos: 28 (12.5%), other 14 (5%). In
      49 patients (21.4%) post-orthotopic liver transplantation passive prophylaxis
      with anti-HBs immunoglobulins was not followed, while in 179 patients the anti
      HBs serum titer was kept above 100-200 mU/ml. Overall 5-year actuarial survival
      of the series was 54%. One hundred and eighty-five patients were evaluable for
      HBsAg reappearance in the serum at various intervals after orthotopic liver
      transplantation. Overall 3-year HBV-free survival of these patients was 55%.
      There was a significant difference in 3-year HBV-free survival between HBV-DNA
      neg (52%), HBV-DNA pos (13%) and Delta pos (73%) patients (p: 0.03). Sixty-three
      percent of patients in the prophylaxis group were HBV-free, compared to only 25%
      of untreated patients (p < 0.001). Three-year HBV-free survival in patients with
      or without HCC was 44% and 59%, respectively. Cox-multivariate analysis revealed
      that only post-transplantation prophylaxis (p: 0.003) and pre-transplantation
      viral activity (p: 0.004) can be considered as independent factors affecting HBV
      recurrence. Candidates with hepatocellular carcinoma in HBV-cirrhosis should not
      be excluded from orthotopic liver transplantation, supporting the idea of a
      higher risk of post-transplantation viral reactivation.

PMID- 8740846
TI  - Apoptosis and proliferation of human hepatocellular carcinoma.
AB  - To investigate the contribution of apoptosis, a major mechanism of cell death, in
      the growth of hepatocellular carcinoma, we analyzed both apoptosis and cell
      proliferation in human hepatocellular carcinoma. We used the terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method and
      proliferative cell nuclear antigen staining, respectively. Among 21
      hepatocellular carcinoma specimens examined, four were well, ten were moderately,
      and seven were poorly differentiated hepatocellular carcinoma. Terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive
      cells in hepatocellular carcinoma were scattered individually or were sometimes
      clustered in the tumors. The terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick end labeling indices were 0.35 +/- 0.09, 0.81 +/- 0.29, and 1.9 +/-
      0.94 in well, moderately, and poorly differentiated hepatocellular carcinoma,
      respectively. The proliferative cell nuclear antigen labeling indices were 6.6 +/
      0.9, 13.1 +/- 3.5, and 26.7 +/- 6.3 in hepatocellular carcinoma in the same
      respective order of differentiation. The differences in both terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling indices and
      proliferative cell nuclear antigen labeling indices (p < 0.05) were significant
      between well, moderately and poorly differentiated hepatocellular carcinoma.
      There was a positive correlation between the terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end labeling and proliferative cell nuclear
      antigen labeling indices in hepatocellular carcinoma (r = 0.84, p < 0.001). This
      study showed that the proliferation rate and the incidence of apoptosis increased
      as the differentiation grade of hepatocellular carcinoma was lowered, suggesting
      a rapid turnover of cancer cells in the lower differentiation grades. Apoptosis
      may thus play an important role in the growth of hepatocellular carcinoma.

PMID- 8740847
TI  - Expression of apolipoprotein A-1 mRNA in normal intrahepatic biliary tree.
AB  - Our previous study demonstrated that apolipoprotein A-1 (apo A-1) immunoreactive
      peptides were located diffusely in the cytoplasm, not only of human normal
      hepatocytes, but also of intrahepatic bile ducts and peribiliary glands. It is
      important to determine whether the presence of these immunoreactive peptides in
      intrahepatic biliary tree is caused by pinocytosis from the bile, or by
      intracellular protein synthesis. Thus, we investigated whether apo A-1 is
      synthesized by cells that line the biliary tree. Normal human liver samples
      obtained at surgery were used; and the expression and distribution of apo A-1
      mRNA in normal human liver tissues were examined, using in situ hybridization
      histochemistry with a 35S-labeled oligonucleotide probe specific for apo A-1. On
      the autoradiogram, many silver grains were found to be distributed uniformly in
      hepatocytes. In addition, an appreciable apo A-1 mRNA signal was also observed in
      both the surface epithelial lining of the bile ducts and the epithelial cells of
      the peribiliary glands. In conclusion, these findings suggest that the apo A-1
      found in bile is secreted both by hepatocytes and by intrahepatic bile duct cells
      and peribiliary glands.

PMID- 8740848
TI  - Low proliferative activity in macroregenerative nodules: evidence for an
      alternate hypothesis concerning human hepatocarcinogenesis.
AB  - Macroregenerative nodules are commonly thought to be hyperplastic lesions,
      deriving both their large size and premalignant potential from an increased
      proliferative rate. We have previously suggested an alternate model of
      macroregenerative nodule development in which neither size nor premalignant
      potential of macroregenerative nodules would depend on increased proliferation.
      We tested this hypothesis by examining the proliferative activity in
      macroregenerative and surrounding cirrhotic nodules. METHODS: Eighteen
      macroregenerative nodules, including five type I and 13 type II, were
      immunostained for proliferating cell nuclear antigen (PCNA). Type II
      macroregenerative nodules included ten with diffuse large (7) or small (3) liver
      cell dysplasia only and eight containing nodule-in-nodule lesions. Five nodule-in
      nodule lesions met the histologic criteria for hepatocellular carcinoma. PCNA
      labeling indices (PCNA-LIs; percentage positive hepatocyte nuclei/500 randomly
      counted cells) were determined in macroregenerative nodules and the four largest
      adjacent cirrhotic nodules. Nodule-in-nodule lesions were assessed separately
      from the background macroregenerative nodule. RESULTS: 4/5 type I and 12/13 type
      II macroregenerative nodules (exclusive of NIN lesions) had PCNA-LIs lower than
      the mean of surrounding cirrhotic nodules. All nodule-in-nodule lesions, whether
      atypical or overtly malignant, had PCNA-LIs greater than any surrounding nodules.
      In conclusion, macroregenerative nodules have PCNA-LIs indistinguishable from,
      and often lower than, surrounding cirrhotic nodules. Increased proliferative
      activity only occurs with the development of atypia and transition to
      hepatocellular carcinoma. CONCLUSION: Macroregenerative nodules derive neither
      their size nor their premalignant potential from on-going rapid proliferation, a
      finding consistent with our alternate hypothesis of macroregenerative nodule
      development.

PMID- 8740849
TI  - Serum clusterin and vitronectin in alcoholic cirrhosis.
AB  - Clusterin and vitronectin are multifunctional regulatory proteins which both
      serve as complement lysis inhibitors. Previous data have strongly suggested that
      serum vitronectin is mainly produced in the liver, whereas the biosynthetic
      origin for serum clusterin has not been determined. In the present study we aimed
      to determine the role of the liver in producing these proteins and to evaluate
      the proteins as possible markers of liver failure. We therefore quantified
      clusterin and vitronectin in serum from patients suffering from alcoholic liver
      cirrhosis (n = 83), and in serum-free culture supernatants from the hepatoma cell
      line HepG2. The median clusterin concentration was 0.20 g/l in cirrhosis and 0.37
      g/l in the controls, whereas corresponding vitronectin values were 0.19 and 0.26
      g/l, respectively. The concentration of both proteins showed significant
      correlation (p < 0.0001) with disease severity and with established plasma
      markers of hepatic synthetic function, such as albumin and prothrombin complex.
      The clusterin level, but not the vitronectin level, correlated with survival (p =
      0.005). The rates of synthesis of clusterin, vitronectin and C3 from HepG2 cells
      were 0.02, 0.21 and 1.9 micrograms/10(6) cells/24 h, respectively. From the
      present data we conclude that clusterin (as vitronectin and C3) is mainly
      produced in the liver and may be a useful marker in the evaluation of severity of
      liver disease and prognosis of patients with alcoholic cirrhosis.

PMID- 8740850
TI  - Ischemic hepatitis secondary to the spontaneous rupture of a hepatocellular
      carcinoma in a patient with cirrhosis.
AB  - A patient with alcoholic cirrhosis who developed fatal ischemic hepatitis induced
      by hemorrhagic shock, due to the spontaneous rupture of a hepatocellular
      carcinoma, is reported. This was the first manifestation of the hepatic neoplasm.
      To our knowledge, this is the first case report of ischemic hepatitis of this
      origin.

PMID- 8740851
TI  - Update of epidemiology, diagnosis, and treatment of pertussis.

PMID- 8740853
TI  - Early recognition of Streptococcus pneumoniae in patients with community-acquired
      pneumonia.
AB  - The objective of this study was to assess the predictive value of signs,
      symptoms, and rapidly available laboratory parameters for pneumococci in
      community-acquired pneumonia (CAP). A prospective study on patients with CAP who
      were admitted to hospital was conducted. Clinical and laboratory data were
      collected according to a protocol. Two hundred sixty-eight patients aged 18 years
      or older, not living in a nursing home or not admitted to hospital within one
      week of this admission, with a new infiltrate on the chest radiograph consistent
      with pneumonia were included. According to microbiological and serological tests,
      patients were allocated to one of two aetiological groups, Streptococcus
      pneumoniae or "other pathogens". Seventy-three variables were examined for a
      correlation with one of the aetiological categories by means of univariate and
      multivariate analysis. The resulting discriminant function was considered a
      clinical test for which posttest probabilities for pneumococcal pneumonia were
      calculated. Streptococcus pneumoniae was demonstrated in 79 patients and other
      pathogens in 83; no pathogens were detectable in 106 patients. The variables
      "cardiovascular disease", "acute onset", "pleuritic pain", "gram-positive
      bacteria in the sputum Gram stain", and "leucocyte count" correctly predicted the
      cause of CAP in 80% of all cases in both groups. Depending on the prevalence of
      Streptococcus pneumoniae, posttest probabilities for pneumococcal pneumonia were
      up to 90%. It is concluded that data on history, together with the result of the
      Gram stain of sputum and the leucocyte count, can help to distinguish
      Streptococcus pneumoniae from other pathogens causing CAP.

PMID- 8740852
TI  - Prospective study of Streptococcus milleri bacteremia.
AB  - In a prospective study of bacteremia caused by organisms of the Streptococcus
      milleri group a total of 32 adult patients were observed over a seven-year
      period. These patients accounted for 1.6% of all patients diagnosed as having
      significant bacteremia and 17% of all cases of streptococcal (nonpneumococcal)
      bacteremia diagnosed during the study period. Only five patients had polymicrobic
      bacteremia. In 31 cases, a presumed origin of infection was identified, generally
      oral or gastrointestinal disease. There were only six cases of nosocomial
      acquisition. The most common presenting symptom was prolonged fever. The
      following forms of presentation were documented: bacteremia with local
      suppurative infection (56%), bacteremia without local suppurative infection
      (25%), and endocarditis (19%). An associated focus of infection was found in the
      abdominal cavity in 20 cases (62%). The mortality rate was 12.5%. All isolates
      were susceptible to penicillin. Caution is necessary in interpreting a blood
      culture positive for Streptococcus milleri group organisms, since, unlike other
      viridans streptococci, they are rarely contaminants. For this reason patients
      with suppurative processes and/or digestive tract disease must be carefully
      investigated.

PMID- 8740854
TI  - Rapid detection of group B streptococcal colonization of the genital tract by a
      commercial optical immunoassay.
AB  - The performance of a commercial optical immunoassay (OIA) was compared at two
      institutions with that of routine agar and broth culture methods for the
      detection of group B streptococcal (GBS) colonization of the genital tract. The
      Strep B OIA (Bio Star, USA) was used to test 962 vaginal swabs from pregnant
      women for the presence of GBS antigen. The prevalence of GBS vaginal colonization
      in this population was 22.4%. The OIA results were compared with those of culture
      on trypticase soy agar with 5% sheep blood (TSA) and broth enhanced culture (Lim
      broth). Sensitivity and specificity values of the OIA method compared to TSA
      culture alone were 82.5% and 91.8%, respectively. The sensitivity of the OIA
      method was equivalent to that of TSA culture (62.4% vs. 64.4%; p > 0.5, chi 2 =
      0.01) when the data were compared with broth culture. The extent of colonization
      affected the sensitivity of the OIA method: 100% of 4+, 94% of 3+, 96% of 2+, and
      63% of 1+ TSA plates were detected by the OIA test. The commercial OIA method
      demonstrated sensitivity equivalent to that of TSA culture for the detection of
      GBS colonization. The OIA test offers two additional advantages over culture:
      reduced time required to obtain results (30 min vs. days) and the ability to
      detect GBS antigen in samples with compromised viability. The results of this
      study suggest that the Strep B OIA test can be a useful diagnostic tool in the
      management of early-onset GBS disease.

PMID- 8740855
TI  - Effect of specimen collection techniques, transport media, and incubation of
      cultures on the detection rate of Helicobacter pylori.
AB  - Culture and histologic examination are considered "gold standard" methods for the
      detection of Helicobacter pylori, but discrepancies may occur with either method.
      Failure to detect Helicobacter pylori may be due to sampling error, inappropriate
      transport or culture media, or insufficient duration of the incubation period.
      Rates of detection of Helicobacter pylori by culture and histopathologic
      examination of gastric mucosal biopsy specimens were determined in 102
      consecutive dyspeptic patients. In a separate group of 60 patients, rates of
      detection of Helicobacter pylori by culture of antral brushings and the length of
      incubation required in selective and nonselective culture media were studied. In
      the first group of 102 patients, the combination of culture and histologic
      examination detected 54 Helicobacter pylori-positive patients, whereas the
      separate techniques each detected 51 Helicobacter pylori-positive patients. In
      the second group of 60 patients evaluated by culture of antral brushings, the
      rate of detection of Helicobacter pylori was 25 of 60 and was similar for culture
      (25/60) and histologic examination (25/60). In the second group the length of
      incubation required to detect Helicobacter pylori was different for selective and
      nonselective media. In nonselective media, incubation of up to ten days was
      required to detect all Helicobacter pylori infections, whereas in selective media
      seven days was sufficient. Rates of detection of Helicobacter pylori by culture,
      histopathologic examination and culture from brushings were similar, whereas the
      combination of culture and histopathologic examination achieved a superior rate
      of detection. The incubation period required for the detection of Helicobacter
      pylori by culture was a minimum of seven days and was dependent on the culture
      medium used.

PMID- 8740856
TI  - Morphologic conversion of Helicobacter pylori from bacillary to coccoid form.
AB  - The morphologic conversion of Helicobacter pylori from bacillary to coccoid form
      was studied by microscopy, viable count on agar plates, and bioluminescence assay
      of bacterial ATP. When morphologic conversion from bacillary to coccoid form was
      detected by microscopy, the viable counts and the bacterial ATP decreased. No
      viable count was found after nine days of incubation, but bacterial ATP was still
      present. In these cultures in which only the coccoid form of Helicobacter pylori
      was present, there was no accumulation of extracellular ATP, indicating no leaky
      cells. During the transition phase from the bacillary to the coccoid form of
      Helicobacter pylori, the addition of fresh medium increased the intracellular ATP
      26-fold. The coccoid form of Helicobacter pylori had a 1000-fold lower ATP level
      per cell compared to the bacillary form, which indicates a decreased metabolic
      activity in the coccoid form. Addition of fresh medium to the coccoid cultures
      from days 9 and 10 increased the ATP level twofold. However, no conversion from
      coccoid to bacillary form was found in these cultures during prolonged incubation
      in fresh broth for four weeks. Such conversion needs to be demonstrated before it
      is proven that the coccoid form of Helicobacter pylori is responsible for
      transmission and relapse of infection.

PMID- 8740857
TI  - Discriminatory power and application of ribotyping of Yersinia enterocolitica O:3
      in an epidemiological study.
AB  - Ribotyping performed with five restriction endonucleases was used in an attempt
      to subtype Yersinia enterocolitica serotype O:3 and also as a tool for clonal
      analysis. DNA from organisms under study (48 isolates from diarrheic human feces,
      24 from food, and 5 reference strains) was tested by Southern hybridization using
      a DNA probe carrying an rRNA operon from Escherichia coli. Strains were grouped
      into seven ribotypes by the HindIII restriction endonuclease, into five ribotypes
      by Ncil, Bg/l, and Sa/l; and into two ribotypes by EcoRI, resulting in a
      discrimination index (DI) of 0.37, 0.17, 0.43, 0.13, and 0.03 for the five
      endonucleases. By combining the results obtained with two or more restriction
      endonucleases, a further discrimination was registered, the most efficient
      combination (in terms of discriminatory power vs. cost in work, time, and money)
      for routine typing being HindIII-Bg/l (9 types, DI=0.58). In the clonal analysis,
      results obtained with the five restriction endonucleases allowed us to define 11
      groupings or clonal lines, which showed a remarkable degree of genetic
      heterogeneity (genetic distance coefficients between 0.03 and 0.73) and were
      grouped into two major clusters. One cluster included 93% of the strains and
      eight lines. At least two of the most frequent lines can be considered endemic in
      Asturias, Spain, because organisms belonging to these lines have been circulating
      and causing human yersiniosis in recent years and have also been isolated from
      commercial raw meat products. Two Ncil ribotypes from the series under study
      (92.2% of strains included in the prevalent cluster) were similar but not
      identical to ribotypes of 0.3 organisms from other geographic areas described in
      the literature, indicating that the genetic structure of prevalent human
      pathogens of this serotype is basically clonal.

PMID- 8740858
TI  - Clinical manifestations and molecular epidemiology of Vibrio vulnificus
      infections in Denmark.
AB  - The clinical manifestations of and epidemiological data from 11 patients infected
      with Vibrio vulnificus admitted to Danish hospitals during the unusually warm
      summer of 1994 are reported. All patients contracted the disease after exposure
      to seawater; however, none had consumed seafood. Four patients developed
      bacteremia, one of whom subsequently died; nine patients, including the four with
      bacteremia, exhibited skin manifestations. Four patients contracted the disease
      while fishing; in at least one case the patient had handled eels. All Vibrio
      vulnificus strains were highly susceptible to 11 antimicrobial agents tested.
      Plasmid analysis revealed that 8 of 11 strains carried plasmids. Ribotyping using
      the enzyme HindIII on the 11 strains showed five different types, two of which
      comprised four strains each. The present study provides the first clinical and
      epidemiological data about a series of human Vibrio vulnificus infections from a
      temperate zone.

PMID- 8740859
TI  - Microbiological contamination of drinking water in a commercial household water
      filter system.
AB  - The microbiological quality of filtered water in a commercial water filter system
      (Brita) was tested in households and in two laboratories. In 24 of 34 filters
      used in households, bacterial counts increased in the filtered water up to 6,000
      cfu/ml. In 4 of 6 filters tested in the laboratory, bacterial counts in the fresh
      filtrate were higher than in tap water after approximately one week of use both
      at room temperature and at 4 degrees C, suggesting growth or biofilm formation in
      the filter material. In some cases colony counts in the filtered water were
      10,000 times those in tap water. The filter material of 5 of 13 new commercial
      filters was contaminated with bacteria or moulds. National or international
      regulatory agencies should ensure that water filters marketed for domestic use do
      not allow deterioration in the microbiological quality of drinking water.

PMID- 8740860
TI  - Fluconazole treatment of candidal infections caused by non-albicans Candida
      species.
AB  - Fluconazole is an effective alternative to amphotericin B for the treatment of
      serious infections caused by Candida albicans. Through a literature survey of
      candidal infections caused by non-albicans Candida spp., 43 cases treated with
      fluconazole were found. The most common causative organisms were Candida
      parapsilosis (14 patients), Candida glabrata (12 patients), and Candida
      tropicalis (11 patients). The dose of fluconazole varied from 50 to 400 mg daily.
      The median duration of treatment was 21 days. Overall efficacy was 77%. The
      efficacy against the various species was 93% for Candida parapsilosis, 50% for
      Candida glabrata, and 82% for Candida tropicalis. In conclusion, fluconazole is
      effective against the most common non-albicans Candida spp., although higher
      doses may be required for infections caused by Candida glabrata. Infections
      caused by Candida krusei should not be treated with fluconazole.

PMID- 8740861
TI  - Evaluation of the anthraxin skin test for diagnosis of acute and past human
      anthrax.
AB  - A skin test for the diagnosis of human anthrax was evaluated as an alternative to
      bacteriological confirmation of human anthrax, which is possible in 10-40% of
      cases within the first three weeks of the disease only. The anthraxin skin test,
      which detects anthrax cell-mediated immunity, was positive in 81.8% of cases in
      the first three days of the disease, and in 97-99% of cases in the next two to
      three weeks. The positivity rate was 98.5% in the first 1.5 months of
      convalescence, 92.8% in the next 3 years, 82.8% in the following 4 to 15 years,
      and 72.7% 16 to 31 years after recovery. Thus, the anthraxin skin test appears to
      be a valuable method for early diagnosis of acute anthrax as well as the only
      method available for retrospective diagnosis of human anthrax.

PMID- 8740862
TI  - Detection of SHV-5 extended-spectrum beta-lactamase in Klebsiella pneumoniae
      strains isolated in Italy.
AB  - Thirty-five Klebsiella pneumoniae strains isolated during 1993-1994 in intensive
      care units of a large Italian hospital were examined for the presence of extended
      spectrum beta-lactamases. Five strains showed a high level of simultaneous
      resistance to beta-lactam agents, including ceftazidime and aztreonam, conferred
      by a large (130 kb) self-transferable plasmid (in 4 of 5 strains).
      Isoelectrofocusing and hybridisation studies suggest that these enzymes can be
      identified as SHV-5 extended-spectrum beta-lactamases. Pulsed-field get
      electrophoresis analysis showed three different genomic fingerprinting profiles,
      while plasmid restriction enzyme digestion revealed three different patterns,
      demonstrating that the diffusion of SHV-5 beta-lactamase is not the result of a
      single strain or plasmid dissemination.

PMID- 8740863
TI  - Prevalence of hepatitis B virus infection in pregnant Turkish women and their
      families.
AB  - A total of 5,366 pregnant Turkish women were screened for hepatitis B surface
      antigen (HBsAg) and 225 (4.2%) of them were found to be positive. Hepatitis B e
      antigen (HBeAg) was detected in 6.2% of HBsAg-positive pregnant women. the
      overall prevalence of HBsAg and antibody to HBsAg (anti-HBs) among the spouses,
      previous children, mothers and first degree relatives of the HBsAg-positive
      pregnant women was 56%, 49%, 79% and 74% respectively. The prevalence of HBsAg is
      thus high in pregnant Turkish women with familial clustering of hepatitis B virus
      infection.

PMID- 8740864
TI  - The validity of Spanos' and Hoen's models for differential diagnosis of
      meningitis.

PMID- 8740865
TI  - Thrombotic microangiopathy related to infection in an HIV-positive patient.

PMID- 8740866
TI  - Systemic Penicillium marneffei infection in a German AIDS patient.

PMID- 8740867
TI  - Nosocomial bacteremia due to vancomycin-resistant Staphylococcus epidermidis in
      four patients with cancer, neutropenia, and previous treatment with vancomycin.

PMID- 8740868
TI  - Bactericidal activity of tyrothricin against methicillin-resistant Staphylococcus
      aureus with reduced susceptibility to mupirocin.

PMID- 8740869
TI  - Frequency of subclinical visceral leishmaniasis in HIV-1-infected patients in
      Spain.

PMID- 8740870
TI  - The concept of equity in health services research.
AB  - A population approach and the general right to health and medical care have been
      important issues in the development of health policy over many centuries.
      However, equity is still a crucial issue in the planning and evaluation of health
      care. Many definitions and criteria related to equity have been formulated on the
      basis of conflicting theories and models. Three dimensions of fair and just
      resource allocation are essential when needs-based models are used: equity in
      access, utilization, and quality of care relative to needs. Health services
      research should concentrate on such outcome measures regarding equity and the
      effect of organizational and processual characteristics of health care systems.
      Prominent examples of such research efforts are presented, but, unfortunately,
      there are few reliable and systematic data from this kind of study. Health care
      researchers have a special responsibility towards the population at large to
      undertake qualified research on equity and to communicate the results to the
      general public.

PMID- 8740871
TI  - The logic of causation in epidemiology.
AB  - The paper attempts to model causality with logical conditionals by way of
      conditional probability. This provides a broad conceptualisation of causality
      according to which we merely observe tendencies toward sufficiency or tendencies
      toward necessity. Cohort studies evaluate the first tendencies, and case-control
      studies the latter. This conceptual approach also clarifies the logic of what
      unifies the two methods. Ways to measure causal tendencies are proposed. Some of
      the consequences of this conceptual analysis are discussed and among them, the
      growing role of chance instead of determinism in science and, although rarely
      acknowledged yet, in epidemiology.

PMID- 8740872
TI  - Risk factors for cerebral palsy: a case-control study in Greece.
AB  - The purpose of this study was to investigate the relation between a series of
      maternal, antenatal, perinatal, socioeconomic and environmental variables and the
      occurrence of cerebral palsy (CP) in a setting different from those in which
      previous analytic epidemiologic studies had been undertaken. The study was of
      case-control design and included 103 children with cerebral palsy born between
      1984 and 1988 and residents of the Greater Athens area at any time during 1991
      and 1992. Controls were chosen among the neighbors of the index case or were
      healthy siblings of children with neurological diseases other than CP seen by the
      same neurologists as the children with CP; a total of 254 control children were
      eventually included. Statistical analysis was done by modeling the data through
      unconditional logistic regression. Statistically significant (p < 0.05) risk
      factors of potential causal importance were: twin membership (OR = 10.2),
      gestational age (OR = 0.5 per 4 weeks), birth weight conditional on gestational
      age (OR = 0.9 per 100 g), congenital malformations (OR = 7.5), unhealthy placenta
      (OR = 6.6), placenta previa (6 cases, no controls), abnormal amniotic fluid (OR =
      3.6), head circumference more than 36 cm (OR = 9.0), general anesthesia during
      labor (OR = 4.3), forceps delivery (OR = 6.8), and birth trauma (OR = 11.5).
      Among children with no identifiable prenatal risk factors there was no excess
      prevalence of one or more perinatal risk factors in CP cases compared to
      controls, which implies that the latter factors impart their effect through
      interactions with co-existing prenatal or other risk factors.

PMID- 8740873
TI  - Sex differences in sickness absence in relation to parental status.
AB  - The aim of this study was to analyse sex differences in medically certified
      sickness absence with special regard to parental status and age. All new sick
      leave spells exceeding seven days and certified by a physician in a county of
      Sweden were registered in 1985-1987. The data-base was related to the population
      at risk by using data from the Swedish Official Population and Housing Census
      1985. The analysis concerned the employed population in the age group from 16 to
      54 with and without custody of children younger than ten years. In all ages,
      women with children had more sickness absence than men with children.
      Corresponding sex differences did not appear for persons without children, except
      for the oldest age-groups. Men with children had the lowest sickness absence of
      all groups. Young women with children had the highest. These findings remained
      the same when pregnancy-related sickness absence was excluded. The common finding
      of sex differences in sickness absence is here highly interrelated to custody of
      small children. The results suggest that the often reported positive health
      effects of multiple roles in women may be counteracted by inequality between the
      sexes in the responsibility as parents.

PMID- 8740874
TI  - Marital status as a risk factor for fetal and infant mortality.
AB  - In order to study pregnancy outcome for married versus unmarried mothers when
      controlling statistically for maternal age, educational level, socioeconomic
      status and income, a total of 93,800 firstborn singleton births in 1978-1982 were
      examined. The unmarried mothers were younger, less well educated and had a lower
      socioeconomic status than the married mothers. The stillbirth, neonatal, and
      postneonatal mortality rates were higher among offspring of unmarried mothers.
      After taking sociodemographic factors into account, marital status was found to
      be associated with postneonatal mortality. The adjusted odds ratio for
      postneonatal mortality was 1.5. Our results indicate the importance of marital
      status as a demographic risk factor even in a welfare society. There is a need to
      identify specific risk behaviours associated with the life styles of unmarried
      mothers. Hopefully our findings will provide information that can be used for
      future programmes of prevention, especially for the mother and her child during
      the first year of life.

PMID- 8740875
TI  - Psychosomatic symptoms in human service work. A study on Swedish social workers
      and social insurance personnel.
AB  - This study reports on subjective health of personnel in human services and other
      occupations. A mail questionnaire was sent to 8296 employees in the Social
      Insurance Organization (SIO) and the Individual and Family Care (IFC) in social
      welfare agencies. The response rate was 69.1% or 5730 persons. Perceived health
      was measured by a standard form widely used in occupational health services,
      FHV004D, here split into four principal components, indicating psycho-vegetative,
      musculoskeletal, immunological, and gastro-intestinal health. In relation to
      reference data on other human service personnel (nurses, teachers) and white
      collar workers (bank and insurance personnel), the studied groups scored much
      higher on psycho-vegetative symptoms (OR:s about 3), higher on musculo-skeletal
      symptoms (OR:s about 1.7), but had equal scores on the other symptom types. It is
      concluded that self-reported psychovegetative and musculoskeletal health is
      especially problematic in SIO and IFC, indicating stress in human service work.
      It is hypothesized that an adversary relation to clients can be an aggravating
      factor in that context.

PMID- 8740876
TI  - Fertility patterns according to occupational grouping in Norway, 1989.
AB  - In the early 1990s, most pregnant women in Norway were in gainful employment.
      This led to increased interest in the possible consequences for reproductive
      health, and a growing concern for the need to accommodate the pregnancy. We have
      therefore investigated how accurately general fertility rates predict the number
      of pregnancies in the workforce. Fertility rates (FR) among employed women and
      standardized fertility ratios (SFR) in occupational groups were estimated on the
      basis of information from the Labour Market Statistics and the national survey
      "Pregnancy and Work", Norway, 1989. The fertility rate among employed women was
      17% higher than the general fertility rate. Two occupational groups had
      significantly different SFRs: technical/professional workers (SFR 118) and
      transport/communication workers (SFR 82). In addition, differences were found for
      parity-specific SFRs in administrative/executive work (SFR nullipara 80, SFR para
      125) and service work (SFR nullipara 114, SFR para 80). We suggest that work
      status and occupation should be included among the variables registered in the
      Medical Birth Registry of Norway, in order to facilitate routine presentations of
      fertility rates and pregnancy outcomes for women in paid work. The results
      further indicate that work-specific conditions influence first-birth fertility.
      This should be explored in demographic studies of the relation between women's
      fertility and participation in paid work.

PMID- 8740877
TI  - Effects on birthweights of maternal education, socio-economic status, and work
      related characteristics.
AB  - Birthweights of 3,451 infants of women registered for antenatal care in Uppsala
      County, Sweden, were analyzed using three different maternal socio-economic
      indicators; education, socio-economic status and work environment exposure
      characteristics. Other explanatory variables were maternal age, parity, height,
      smoking habits, and length of gestation. Mean birthweights increase with longer
      education and higher socio-economic status. No general pattern was seen for work
      environment characteristics. When smoking habits are controlled for, social
      differences in birthweight decrease to non-significant values. A regression model
      with a socio-economic indicator alone explains only a minor part, less than 1%,
      of the variation in birthweight. When smoking is included, adding a socio
      economic indicator does not significantly improve the model. Practically all
      social differences in birthweight are related to the differences in maternal age,
      parity, height, and smoking habits. If a socio-economic indicator is to be
      included in the analysis of birthweights (for other reasons like international
      comparisons), we recommend education.

PMID- 8740878
TI  - Breast-feeding in Iceland. Predictive factors and effects of interventive
      measures.
AB  - The aim of this study was to analyse how long babies born in Akureyri district in
      1990 were breast-fed, compared with babies born in 1985. Possible predictive
      factors for the length of breast-feeding were studied by univariate and
      multivariate analyses. From 1985 to 1990, the proportion of infants exclusively
      breast-fed at the age of 3 months increased from 57% to 70% (p < 0.01) and for
      those breast-fed exclusively or partially, from 67% to 83% (p < 0.01). By 1990,
      64% of all babies were breast-fed at the age of 6 months, compared with 43% in
      1985 (p < 0.01). The factor with the strongest correlation with a long breast
      feeding period was a well educated father. Other factors correlated with the
      duration of breast-feeding were the mother's age, number of previous children,
      attending a maternity course, and being a non-smoker. It is concluded that real
      beneficial changes regarding the duration of breast-feeding in Iceland have been
      observed during the last decade, but the objectives of the preventive measures
      recommended by health authorities have not yet been reached.

PMID- 8740879
TI  - Multivariate analyses of mortality from coronary heart disease due to biological
      and behavioural factors.
AB  - Due to affluence and a sedentary life style a great deal of people in the western
      countries are affected by coronary heart disease (CHD). The relation between CHD
      and certain risk factors pertaining to life style is evaluated in this study. A
      primary purpose is to study certain crucial risk factors for women. The main
      variables are age, smoking, overweight (measured by BMI), blood pressure and
      exercise. This prospective study is based on self-reported data from the nation
      wide Swedish Level of Living Survey and on data from the national Cause of Death
      Register. The data were analysed separately by sex using a proportional hazards
      model. The sample was divided into two strata: those with heart disease and/or
      diabetes initially, and all the rest. A sample of 2546 men and 2760 women between
      45 and 74 years of age was followed from 1980 to the end of 1990. During this
      period 189 men and 75 women died of coronary heart disease (CHD). It was found
      that high blood pressure raised the relative risk (RR) of death from CHD by
      almost 60% in both men and women. Male smokers (> 14 cigarettes a day) had about
      60% (significant) and female smokers (> 10 cigarettes a day) 150% (significant)
      excessive mortality from CHD. Different levels of overweight among women were
      strongly related to excess mortality from CHD, ranging between 100 and 300%.
      Among men there was no such relation. Lack of physical activity showed only a
      weak (non-significant) increased risk of death due to CHD. Diabetes was also
      found to be an important risk factor for mortality from CHD, especially among
      women, being seven times as high as among non diabetics. A test of sex
      differences revealed that there were two significant interactions, namely between
      sex and overweight, and between sex and age. Background variables in relation to
      mortality from all cardiovascular diseases (CVD) were also studied. There were of
      course many similarities between the effects of the background variables in both
      the disease groups, but there were interesting differences too, e.g. overweight
      turned out to be a significant risk factor also for men and physical inactivity
      for women.

PMID- 8740880
TI  - Cardiovascular risk differences among employed and unemployed village people in
      Hungary.

PMID- 8740881
TI  - Reification and synergy in clinical ethics and its adequacy to the managed
      practice of medicine.

PMID- 8740882
TI  - Four approaches to doing ethics.
AB  - Within the field of medical ethics there is a startling amount of diversity
      regarding which issues and relationships are deemed relevant for ethical inquiry
      and analysis, what strategies are appropriate for examining and resolving ethical
      conflict, what should be the goals for medical ethics, even who should
      participate in that project. What I will try to make clear in this paper is that
      how we go about this process of doing medical ethics, of examining, reflecting,
      decisionmaking, and behaving, makes a practical difference, and not just a
      philosophical one, in terms of the understandings we will reach about ethical
      matters. Without attempting to resolve any of the conflicts within or between
      different conceptions of doing ethics, I will try to articulate the differences
      in orientation, and particularly the tone and educational emphasis, that attend
      four major contemporary approaches to ethical inquiry and analysis: deductivism,
      principlism, modern casuistry, and feminist/relationist ethics.

PMID- 8740883
TI  - A linguistic model of informed consent.
AB  - The current disclosure model of informed consent ignores the linguistic
      complexity of any act of communication, and the increased risk of difficulties in
      the special circumstances of informed consent. This article explores, through
      linguistic analysis, the specificity of informed consent as a speech act, a
      communication act, and a form of dialogue, following on the theories of J.L.
      Austin, Roman Jakobson, and Mikhail Bakhtin, respectively. In the proposed model,
      informed consent is a performative speech act resulting from a series of
      communication acts which together constitute a dialogic, polyphonic,
      heteroglossial discourse. It is an act of speech that results in action being
      taken after a conversation has happened where distinct individuals, multiple
      voices, and multiple perspectives have been respected, and convention observed
      and recognized. It is more meaningful and more ethical for both patient and
      physician, in all their human facets including their interconnectedness.

PMID- 8740884
TI  - Arguing along the slippery slope of human embryo research.
AB  - One frequent argument in the debate over federal funding of human embryo research
      is the slippery slope argument. Slope arguments can be of several types: either
      logical, empirical, or full (a combination of logical and empirical slope
      arguments, with an additional psychological premise). A full slope argument
      against human embryo research suggests that funding embryo research could
      undermine current protections for human subjects research, erode respect for
      persons with disabilities, and encourage eugenics practices. While the Panel
      commissioned by the National Institutes of Health to issue funding guidelines
      regarding human embryo research acknowledges some slippery slope concerns, the
      Panel's final report fails to address such concerns in any depth. Given this
      failure seriously to address these valid concerns, federal funding of embryo
      research should not proceed at this time.

PMID- 8740885
TI  - Pharmaceutical sales representatives and physicians: ethical considerations of a
      relationship.
AB  - Since their appearance in 1850, Pharmaceutical Sales Representatives (PSR)
      interactions with physicians have engendered intense emotional responses. The
      controversy has continued unabated since that time. Arguments in favor of the
      moral impermissibility of the PSR-physician relationship can be divided into four
      general categories; (1) influence, (2) patients pay but they do not choose, (3)
      violation of principlism, and (4) the erosion of the patient-physician
      relationship. None of the arguments that have thus far been proposed against the
      moral permissibility of these interactions gives sufficient warrant to avoid them
      (or pursue them). It may be the case that PSR-physician interactions place the
      patient-physician relationship in jeopardy. This would constitute enough warrant,
      from a pragmatic perspective, to shun such relationships. However, no research
      supports this contention. A careful evaluation of the literature leaves one
      ambivalent at best.

PMID- 8740886
TI  - Community participation in the control of tropical diseases.

PMID- 8740887
TI  - Paradigms lost: toward a new understanding of community participation in health
      programmes.
AB  - Community participation has been a critical part of health programmes,
      particularly since the acceptance of primary health care as the health policy of
      the member states of the World Health Organisation. However, it has rarely met
      the expectations of health planners/professionals. This paper argues that the
      reason for this failure is that community participation has been conceived in a
      paradigm which views community participation as a magic bullet to solve problems
      rooted both in health and political power. For this reason, it is necessary to
      use a different paradigm which views community participation as an iterative
      learning process allowing for a more eclectic approach to be taken. Viewing
      community participation in this way will enable more realistic expectations to be
      made. Community participation in disease control programmes focusing on community
      health workers is used as an example to show the limitations of the old paradigm.
      Participatory rapid appraisal is used to illustrate the new.

PMID- 8740888
TI  - Health education to promote community involvement in the control of tropical
      diseases.
AB  - Health Education is any combination of learning activities that promote voluntary
      adaptations in health-related behaviour. In pursuing this definition, health
      workers generally work in two main directions, a community development approach
      and a behavioristic, communications approach. While Health Education in tropical,
      developing countries often takes the developmental approach with full community
      involvement, including the setting of programme priorities, Health Education for
      disease control has more often been characterized as the behavioristic mode
      utilizing simplistic, professionally determined messages and short-term campaigns
      to attempt to influence health behaviours related to disease transmission.
      Efforts in Idere, Nigeria, have tried to merge the two approaches building on
      community concern about one endemic tropical disease, Guinea worm. From this
      base, volunteer village health worker (VHW) training was developed. VHWs, once
      trained, developed their own association, which served as an organizational base
      for further health development programming, directed by the VHWs themselves.

PMID- 8740889
TI  - Community-based approach to schistosomiasis control.
AB  - With few exceptions, efforts to control schistosomiasis have relied upon ongoing
      community cooperation with "outsiders' rather than creating within the community
      the capacity and means for carrying out ongoing disease control measures with
      minimal external support. Offered as a useful model is a program in Kaele
      subdivision, Extreme North Province, Cameroon designed to establish and integrate
      within the primary health care (PHC) system the control of urinary
      schistosomiasis, hyperendemic in the region. At the community level, and with
      minimal dependence upon external resources, culturally appropriate and effective
      health education was instituted, the capacity to diagnose and treat
      schistosomiasis was created, diagnosis and drug therapy (praziquantel) was made
      available conveniently and at low cost, and, on a very limited basis, snails were
      controlled. Efforts were made to build upon and strengthen existing community
      structures and institutions rather than create new ones. The impact of the
      interventions was measured in terms of changes in knowledge and behavior,
      prevalence and intensity of infection, utilization of health services, and the
      ability to finance the control activities within the context of a generalized
      cost recovery system. Program successes and failures are discussed, as well as
      lessons learned and their implications.

PMID- 8740890
TI  - Community participation in the eradication of guinea worm disease.
AB  - As Guinea worm eradication programmes have got under way in endemic countries
      over the last decade, there has been a shift towards more participatory methods.
      The approach to surveillance has changed from periodic cross-sectional surveys to
      monthly village-based reporting of cases by a volunteer village health worker. At
      the same time, the emphasis regarding control interventions has moved from the
      provision of safe water supplies to health education. The new approach has proved
      very effective. The village health volunteers who carry out both surveillance and
      health education seem to be motivated largely by the social status of their role;
      still more commitment will be required of them in the final stages of
      eradication. It is to be hoped that the networks of village health workers
      established for Guinea worm eradication will find a useful role in health
      promotion after the worms have gone.

PMID- 8740891
TI  - Community-based ivermectin distributors: onchocerciasis control at the village
      level in Plateau State, Nigeria.
AB  - The use of community residents as agents for distributing mass ivermectin therapy
      for onchocerciasis provides a component of community participation absent from
      mobile team delivery methods. Community-based distribution, however, presupposes
      preexisting human resources in the endemic villages capable of fulfilling the
      essential functions of an ivermectin distribution process: mobilizing and
      educating the population, dispensing the drug, maintaining records, and
      monitoring and treating adverse reactions. Even when such human resources exist,
      the community workers must continue to receive tangible support from both
      external (government and donor agencies) and internal (community) sources. Donor
      and government agencies must accept that their data collection demands will be
      limited by the literacy standards of the communities being served. Community
      leaders must agree to set and use their own local standards of payment (including
      food stuffs or exchange in kind) to compensate the distributors for their time
      and efforts. The use of locally available human and remunerative resources is a
      prerequisite for true community ownership of a program.

PMID- 8740892
TI  - Community participation in malaria control in Tigray region Ethiopia.
AB  - During the Ethiopian civil war from 1974 to 1991, the Tigrean People's Liberation
      Front established a primary health care system in Tigray in which community
      residents helped to plan and implement health services through health committees
      and community health workers (CHWs). To strengthen and update this system, a
      Community-Based Malaria Control Programme was initiated in 1992. The primary
      objectives of the Programme are to reduce malaria morbidity and mortality and to
      prevent malaria in pregnant women through early diagnosis and treatment of cases,
      chemoprophylaxis during pregnancy, and vector control by environmental
      management. A secondary objective is to introduce a cost-sharing scheme for
      eventual development of a village revolving fund. A total of 681 volunteers
      chosen by their communities have received malaria training and serve a rural
      population of 1,682319 (CHW/population ratio 1:2,500). The principal success of
      the programme at this stage is that a significant proportion of the rural
      population at risk for malaria is now being treated at the village level. During
      the last major transmission season from September through November 1993, each
      CHWs treated a mean of 45178 clinical malaria cases per month. Under-utilization
      of treatment services by women and children under 5 years and low
      chemoprophylaxis coverage of pregnant women have been documented. After focus
      group discussions with community members and CHWs to identify the reasons for
      these problems, changes in programme policies were made to improve coverage of
      these groups. Since 1992, considerable progress toward meeting programme
      objectives has been made, and continued evaluation will allow for interventions
      that should further strengthen the malaria control efforts in the region.

PMID- 8740893
TI  - Village-based diagnosis and treatment of malaria.
AB  - Village-based volunteer workers have played an important role in malaria
      diagnosis and treatment in many different settings for more than 35 years. Two of
      these programs stand out in terms of their size and longevity: the Volunteer
      Collaborator Network of Latin America and the Village Voluntary Malaria
      Collaborator Program of Thailand. The success of these programs is based on a
      tradition of active community participation and sustained commitment and support
      from the national malaria control programs. As epidemiological conditions and
      program priorities change, these programs will have to be sufficiently flexible
      to keep pace. Perhaps the greatest challenge facing these single disease,
      vertical programs in the future is their integration into the general health
      services in a manner that will preserve their best features.

PMID- 8740894
TI  - Community involvement in the control of Aedes aegypti.
AB  - In the past 15 years, there has been a dramatic resurgence of dengue and dengue
      hemorrhagic fever worldwide, with increased frequency of epidemics and geographic
      expansion of both the mosquito vectors and the viruses. The reasons for this
      resurgence are not well understood, but include uncontrolled and unplanned
      urbanization, increased movement of people and viruses by airplane and lack of
      effective control of Aedes aegypti, the principal mosquito vector of dengue
      viruses. The recommended method for Ae. aegypti control during the past 20 years
      has been ultra-low volume (ULV) application of insecticides, a method which
      targets the adult mosquito. Lack of efficacy of the ULV approach led to a
      reevaluation of recommended strategies for prevention and control of epidemic
      dengue and ultimately, resulted in development and widespread use of community
      based, integrated approaches to Ae. aegypti control. This chapter reviews the use
      of community participation for controlling Ae. aegypti via larval source
      reduction and critically discusses programs in four countries from the standpoint
      of effectiveness and sustainability. It is concluded that a combination of
      vertically structured centralized and community-based approaches should provide
      short-term success as well as long-term sustainability.

PMID- 8740895
TI  - Kell and Xg gene frequencies in Algeria.
AB  - Using micro-methods, we have phenotyped 3590 and 688 Algerians for the KEL and XG
      systems respectively. The gene frequencies were estimated for each of the 26
      "wilayas" (regions) of the country. The KEL*K allele shows a heterogeneous
      distribution throughout the regions (frequencies ranging from 0.0269 to 0.0678)
      with no evident gradient, although within the caucasoid range. The XG*a
      frequencies in the wilayas range from 0.3150 to 0.7778 following an increasing
      south-north cline, thus confirming the intermediate status of Algeria between
      Europe and Africa.

PMID- 8740896
TI  - DBP (vitamin D binding protein) and BF (properdin factor B) allele distribution
      in Namibian San and Khoi and in other South African populations.
AB  - The genetic polymorphism of vitamin D binding protein (DBP) and of properdin
      Factor B (BF) was determined in unrelated Namibian San and Khoi, and in South
      African Blacks, Caucasoids and Cape Coloureds. Alleles have been confirmed by
      segregation patterns in family studies. The DBP phenotypes were identified by
      isoelectric focusing on ultrathin polyacrylamide gels and the BF phenotypes were
      identified by electrophoresis on 1% agarose gels; both methods were followed by
      immunofixation. The DBP and BF allele frequencies for all population groups were
      found to be in accordance with Hardy-Weinberg equilibrium. DBP*1S and BF*S allele
      frequencies in the San, Khoi and Blacks were similar; their frequency was far
      lower than in Caucasoids. The frequencies of the DBP*1F and BF*F were also
      similar in the San, Khoi and Blacks; however, the allele frequency was much
      higher in these groups than in Caucasoids. These differences were statistically
      significant (P < 0.001).

PMID- 8740897
TI  - ITI (inter-alpha trypsin inhibitor) phenotyping by immunogold staining.
AB  - Polymorphism of Inter-alpha-Trypsin Inhibitor (ITI) was investigated in 685
      unrelated Japanese individuals by isoelectric focusing followed by
      electroblotting and immunogold silver staining. The allele frequency estimates
      were ITI*1 = 0.455 +/- 0.013, ITI*2 = 0.516 +/- 0.013, ITI*3 = 0.028 +/- 0.0045
      and ITI*4 = 0.001 +/- 0.001 and the phenotype frequencies fitted the Hardy
      Weinberg equilibrium. The ITI system could be regarded as a potential genetic
      marker in paternity testing and anthropological studies.

PMID- 8740898
TI  - The distribution of the ABO and Rhesus blood groups (phenotype and allele
      frequencies) in the populations of Cyprus.
AB  - The distribution of ABO and Rhesus blood groups in the populations of Cyprus have
      been studied in 47,759 individuals (about 8% of the Greek-Cypriot population).
      The data were classified according to the administrative areas of Cyprus and into
      further 41 smaller units.

PMID- 8740899
TI  - Silent APC (adenomatous polyposis coli) gene polymorphism in the Portuguese
      population.
AB  - We describe a new, silent polymorphism in exon 15 of the APC gene on chromosome
      5q in the Portuguese population. The polymorphism is located at codon 1442 and
      results in a CCT-->CCA (Pro) base transversion, with no amino acid change.
      Population analysis in unrelated healthy controls indicated that the polymorphism
      was present in 2 out of 50 individuals giving an allele frequency of 0.02 +/-
      0.01. The polymorphism is the most common encountered in the Portuguese
      population in the mutation cluster region of exon 15, and has not been previously
      described in other populations.

PMID- 8740900
TI  - Geographic variation analysis of the ABO and RH systems in Turkey.
AB  - In this study, we report the results of a geographical variation analysis on the
      gene frequencies of ABO and RH systems in 67 provinces of Turkey. The gene
      frequencies of A, O and RH(-), were subjected to spatial autocorrelation analysis
      and significant spatial autocorrelation coefficients were observed for each gene
      in the first distance class. The average I-correlogram for the three genes
      displayed a clinal pattern. The results also suggested a marked decrease in
      genetic similarity in relation to geographic distance.

PMID- 8740901
TI  - Trimmatostroma abietis sp. nov. (hyphomycetes) and related species.
AB  - Trimmatostroma abietis from the needles of conifers and from stone, mostly in
      Germany, is described. On the natural substrate it is characterized by stromatic
      conidiomata. Conidia are mostly two-celled, are arranged in long chains, and
      originate by intercalary dilatation of fertile hyphae. The wide morphological
      plasticity of the fungus and its physiological profile are described. Its
      occurrence as a saprophyte and possibly opportunistic pathogen on plants and as
      an invader of environments with low water activity, particularly stone surfaces,
      are discussed. Relationships with other taxa are outlined.

PMID- 8740902
TI  - A new type of growth exhibited by Trimmatostroma abietis.
AB  - Trimmatostroma abietis initially grew as hyphae when grown in various media
      containing yeast extract or bactopeptone. It grew as segmented elements
      (lumbricoid elements) characterized by bidirectional growth, when grown in Czapek
      Dox broth or yeast nitrogen base supplemented with 1% glucose. A lumbricoid
      element usually was 10-70 microns in length, with transverse septation only and
      contained 3 to 15 cells. Growth and propagation, as revealed by time-lapse
      photomicrography occurred as follows. Elements usually grew by apical elongation
      without widening; after simple apical elongation adjacent parts of two central
      cells eventually started to grow, resulting in the separation of the element into
      two.

PMID- 8740903
TI  - Stationary phase development of Trimmatostroma abietis.
AB  - Processes of anamorph cell replication in Trimmatostroma abietis are described.
      Growth and conidiation are delimited on the basis of morphological,
      ultrastructural and ecological criteria. Cellular expansion shifts from
      bidirectional intercalary in exponential phase cells to isodiametric in late
      stationary phase cells, in the latter case with endogenous asexual reproduction.
      Ultrastructural similarities to dothideaceous black yeasts are discussed.

PMID- 8740904
TI  - Molecular differentiation of Keratinomyces (Trichophyton) species.
AB  - The taxonomy of the form-genus Keratinomyces (Trichophyton) within the group of
      the dermatophytes is based on morphological features which remain insufficient
      for the distinction of these anamorphic species. The three species included in
      the genus Keratinomyces, namely K. ajelloi, K. ceretanicus and K. longifusus were
      examined by means of their mitochondrial-like DNA diversity and compared to few
      other dermatophytes. The analysis of the mtDNA restriction fragments confirmed
      that the three species are different and well separate from the other
      dermatophytes.

PMID- 8740905
TI  - Some remarks on "a taxonomic key for the genus Saccharomyces" (Vaughan Martini
      and Martini 1993).
AB  - The practicability of Vaughan Martini and Martini's "Taxonomic Key for the Genus
      Saccharomyces" for the separation of S. bayanus from other Saccharomyces sensu
      stricto species was studied. It was concluded that the ability to grow in vitamin
      free medium was not a suitable character for this purpose. A new wild S. bayanus
      strain, isolated from exudate of Carpinus betulus was also included in this
      study. This appears to be the third documented strain of that species isolated
      outside of an artificial fermentation environment.

PMID- 8740906
TI  - Purification and characterization of two different xylanases from the
      thermophilic actinomycete Microtetraspora flexuosa SIIX.
AB  - Two endoxylanases were isolated from the xylanolytic enzyme system of the
      thermophilic actinomycete Microtetraspora flexuosa SIIX, and purified by ammonium
      sulfate fractionation, DEAE-Sepharose chromatography, gel filtration on Sephacryl
      S 200 and fast protein liquid chromatography on Q-Sepharose. The molecular masses
      of xylanase I and II were 26.3 and 16.8 kDa, and isoelectric points were 8.4 and
      9.45, respectively. Optimal enzyme activities were obtained at 80 degrees C and
      pH 6.0. The thermostability of both xylanases was greatly diminished during
      purification but could be restored by preincubation of the purified enzymes in
      the presence of xylan. The half-lives at 80 degrees C were approximately 25 min.
      The kinetic constants of xylanases I and II determined with Remazol-brilliant
      blue xylan were Vmax of 1537 and 353 mumol.min-1.mg protein-1 and K(m) values of
      2.44 and 1.07 mg.ml-1, respectively. Purified xylanases utilized xylan as well as
      small oligosaccharides such as xylotriose as substrate. They did not exhibit
      xylobiase or debranching activities. The predominant products of arabinoxylan
      hydrolysis were xylobiose and xylotriose, the latter being hydrolysed to
      xylobiose and xylose upon further incubation. In addition, fragments containing
      arabinose side chains accumulated. The xylanases did not act on crystalline or
      amorphous cellulose indicating a possible application in biobleaching processes.

PMID- 8740908
TI  - Metabolic rates during sporulation of Saccharomyces cerevisiae on acetate.
AB  - We have quantified yeast carbon and oxygen consumption fluxes and estimated
      anabolic fluxes through glyoxylate and gluconeogenic pathways under various
      conditions of sporulation on acetate. The percentage of sporulation reached a
      maximum of 55% to 60% after 48 h in sporulation medium, for cells harvested from
      logarithmic growth in acetate minimal medium. When cells were harvested in the
      stationary phase of growth before transfer to sporulation medium, the maximum
      percentage of sporulation decreased to 40% along with the occurrence of meiosis
      as could be judged by counting of bi- and tetra-nucleated cells. In both
      experiments, the rates of acetate and oxygen consumption decreased as a function
      of time when exposed to sporulation medium. Apparently, the decrease of metabolic
      rates was not due to alkalinization. By systematically varying the cell
      concentration in sporulation medium from 1.4 x 10(7) to 20 x 10(7) cell ml-1, the
      percentage of sporulating cells was found to decrease in parallel with the rate
      of acetate consumption. When the sporulation efficiency attained under the
      different experimental conditions was plotted as a function of the rate of
      acetate consumption, a linear correlation was found. Anabolic fluxes estimation
      revealed a decrease of the rate through gluconeogenic and glyoxylate pathways
      occurring during sporulation progression. The pattern of metabolic fluxes
      progressively evolved toward a predominance of more oxidative catabolic fluxes
      than those exhibited under growth conditions. The results obtained are discussed
      in terms of a characteristic pattern of metabolic fluxes and energetics,
      associated to the development of yeast sporulation.

PMID- 8740907
TI  - Techniques for genetic engineering in mycobacteria. Alternative host strains, DNA
      transfer systems and vectors.
AB  - The study of mycobacterial genetics has experienced quick technical developments
      in the past ten years, despite a relatively slow start, caused by difficulties in
      accessing these recalcitrant species. The study of mycobacterial pathogenesis is
      important in the development of new ways of treating tuberculosis and leprosy,
      now that the emergence of antibiotic-resistant strains has reduced the
      effectiveness of current therapies. The tuberculosis vaccine strain M. bovis BCG
      might be used as a vector for multivalent vaccination. Also, non-pathogenic
      mycobacterial strains have many possible biotechnological applications. After
      giving a historical overview of methods and techniques, we will discuss recent
      developments in the search for alternative host strains and DNA transfer systems.
      Special attention will be given to the development of vectors and techniques for
      stabilizing foreign DNA in mycobacteria.

PMID- 8740909
TI  - Behaviour of the yeast Kluyveromyces marxianus var. marxianus during its
      autolysis.
AB  - The lactic yeast Kluyveromyces marxianus var.marxianus (formerly K. fragilis)
      autolyzates at faster rate than Saccharomyces cerevisiae. During K. marxianus
      autolysis, quite similar release kinetics were observed for intracellular space
      markers (potassium ions, nucleotides), cell-wall components (polysaccharides, N
      acetyl-D-Glucosamine) and non specific products (amino nitrogen). By Scanning
      Electronic Microscopy examination, no cell burst was observed, but a variation in
      cell shape (from ellipsoidal to cylindrical), as well as a 43% decrease in the
      internal volume were observed. The mechanism proposed for S. cerevisiae autolysis
      appeared also likely for K. marxianus.

PMID- 8740910
TI  - The flocculation of wine yeasts: biochemical and morphological characteristics in
      Kloeckera apiculata.
AB  - The floc-forming ability of flocculent strains of Kloeckera apiculata, isolated
      from musts, was tested for susceptibility to proteinase and sugar treatments.
      Three different flocculation phenotypes were discriminated by protease digestion,
      whereas the inhibition of flocculation by sugars distinguished two definite
      patterns: one mechanism of flocculation involved a galactose-specific protein and
      the other a broad-specificity lectin. SEM and TEM observation of the cell surface
      of two different Kloeckera strains revealed fine fibrils and a diffuse structure
      at the point of contact in one strain, and thick masses of mucus on the cell wall
      of the other strain.

PMID- 8740911
TI  - Ballistosporous yeasts found on the surface of plant materials collected in New
      Zealand. The genera Bensingtonia and Bullera with descriptions of five new
      species.
AB  - In the present study, strains from the surface of plant materials collected in
      New Zealand that belong to the genera Bensingtonia and Bullera are classified.
      One strain of Bensingtonia was assigned to Ben. ingoldii, while the remaining
      strain was assigned to Ben. naganoensis based on DNA-DNA reassociation
      experiment. Twenty-one of 28 Bullera strains were assigned to B. alba (11
      strains), B. crocea (6 strains) and B. variabilis (4 strains). The remaining
      seven strains could not be assigned to any previously known species and were
      described as the new species, B. coprosmaensis (1 strain), B. hannae (1 strain),
      B. huiaensis (1 strain), B. mrakii (3 strains) and B. unica (1 strain).

PMID- 8740912
TI  - Preimplantation genetic testing for Huntington disease and certain other
      dominantly inherited disorders.
AB  - Preimplantation genetic testing (PGT) on embryos from couples at risk for
      Huntington disease can achieve disease prevention in offspring without disclosure
      of parental genotype. This strategy may also be applicable to other extremely
      deleterious dominant traits.

PMID- 8740913
TI  - Neurofibromatosis/Noonan phenotype: a variable feature of type 1
      neurofibromatosis.
AB  - Since January 1989 we have ascertained patients with neurofibromatosis type 1
      (NF1) as part of our genetic register in the North West of England. This register
      has now identified 453 affected cases from 235 families. The first 94 individuals
      were specifically examined for features of the Noonan phenotype. This was present
      in 12/94 sequentially identified individuals with NF1 including six individuals
      from three families. However, three cases occurred in a further family, where
      Noonan syndrome appeared to segregate separately from NF1. We have provided
      evidence for the chance association of Noonan syndrome and NF1 and that the
      Noonan phenotype occurs as a feature in some NF1 families. However, there is now
      little evidence of a separate NF1/Noonan syndrome entity or of NF1 features
      occurring in classical Noonan syndrome.

PMID- 8740914
TI  - Neuropsychological aspects of Marfan syndrome.
AB  - We evaluated the neuropsychological status of 13 adults patients with Marfan
      syndrome. All subjects were administered the same neuropsychological test battery
      that included nine measures covering a broad range of cognitive abilities such as
      attention and concentration, learning and memory, and verbal and non-verbal
      abilities. Compared to a control group of 13 healthy subjects matched for sex,
      age and verbal intelligence, Marfan patients only performed significantly worse
      on tests measuring sustained visual attention and visuoconstruction. Although
      these tests use visual material and depend on visual perception and processing,
      the visual acuity problems associated with the syndrome could not explain these
      differences, nor could the use of beta-blocking medication or the presence of
      joint hypermobility. The findings suggest that problems with sustained visual
      attention and visuoconstruction may be present in Marfan syndrome over and above
      visual acuity problems and other phenomena associated with the disease. Further
      research on the neuropsychological aspects of Marfan syndrome is needed, using
      larger patient groups and more adequate control groups such as non-affected
      siblings and matched controls with similar visual impairment.

PMID- 8740915
TI  - Phocomelia, ectrodactyly, skull defect and urinary system anomaly: Schinzel
      phocomelia syndrome?
AB  - This report describes a girl with phocomelia of the right upper limb,
      ectrodactyly, sacral hypoplasia and a large skull defect, but with normal growth
      and mental development. Ultrasonography and intravenous pyelography showed
      bilateral hydronephrosis and dilated ureters. We conclude that this patient may
      represent Schinzel-phocomelia syndrome with additional urinary tract anomalies.

PMID- 8740916
TI  - Association analyses of NsiI RFLP of human insulin receptor gene in
      hypertensives.
AB  - Plasma angiotensinogen is elevated in essential hypertensives and shows a strong
      correlation with blood pressure. Patients with hypertension often display insulin
      resistance and we have found previously an association of a RsaI RFLP in intron 9
      of the insulin receptor gene (INSR) with hypertension. Since insulin resistance
      is accompanied by hyperinsulinaemia and insulin can stimulate angiotensinogen
      production, we hypothesized that hypertension-associated genotypes of INSR may be
      associated with elevation in plasma angiotensinogen. We used PCR to detect a NsiI
      RFLP in exon 8 of INSR and examined its relationship with plasma angiotensinogen,
      as well as hypertension, in 134 Caucasian hypertensives with two hypertensive
      parents and in 126 normotensives. Plasma angiotensinogen tracked weakly with the
      major allele of the NsiI RFLP in hypertensives (p = 0.08). Moreover, the
      frequency of this allele was higher in lean hypertensives than in lean
      normotensives (p < 0.05) and in normolipidaemic hypertensives than
      normolipidaemic normotensives (p < 0.02). The present study thus suggests that
      there could be a relationship of plasma angiotensinogen with INSR genotype, and
      of each with hypertension.

PMID- 8740917
TI  - Identification of two apolipoprotein variants, A-I Karatsu (Tyr 100-->His) and A
      I Kurume (His 162-->Gln).
AB  - We identified two apolipoprotein (apo) A-I variants, using isoelectric focusing
      gel electrophoresis: apo A-I Karatsu, which had a relative charge of +1 compared
      to normal apo A-I4, and apo A-I Kurume, which had a relative charge of -1. Direct
      sequence analysis of the PCR-amplified DNA from the proband of apo A-I Karatsu
      revealed a single substitution of tyrosine (TAC) for histidine (CAC) at position
      100. Sequence analysis of apo A-I Kurume revealed a single substitution of
      histidine (CAT) for glutamine (CAG) at position 162. Probands of these two
      mutants and limited family study showed no accelerated atherosclerosis.

PMID- 8740918
TI  - Two novel missense mutations in the LDL receptor gene causing familial
      hypercholesterolemia.
AB  - We have employed analysis of single-strand conformation polymorphisms to identify
      mutations in the low density lipoprotein receptor gene causing familial
      hypercholesterolemia. Two familial hypercholesterolemia heterozygotes had
      abnormal single-strand conformation polymorphism patterns of exons 4 and 8. DNA
      sequencing revealed that the abnormal pattern of exon 4 was due to heterozygosity
      (G/T) at nucleotide 502. Nucleotide 502 is the first base of codon 147, and the G
      >T mutation (D147Y) changes this codon from AspGAC to TyrUAC. The abnormal
      pattern of exon 8 was due to heterozygosity (A/G) at nucleotide 1097. Nucleotide
      1097 is the second base of codon 345, and the A->G mutation (Q345R) changes this
      codon from GlnCAG to ArgCGG. Based upon screening of 437 unrelated familial
      hypercholesterolemia heterozygotes, both D147Y and Q345R account for about 0.5%
      of the mutations causing familial hypercholesterolemia in Norway.

PMID- 8740919
TI  - An Iranian-Armenian LDLR frameshift mutation causing familial
      hypercholesterolemia.
AB  - We used polymerase chain reaction single-strand conformation polymorphism (PCR
      SSCP) analysis to detect a mutation in the low density lipoprotein receptor
      (LDLR) gene in a family of Iranian-Armenian origin. The mutation, designated FH
      Yrmeih, deletes two nucleotides from exon 10 of the LDLR gene, which causes a
      translational frameshift, whereby a truncated LDLR protein of the first 471
      residues of the LDLR with an additional 41 abnormal residues and a premature stop
      codon would be created. The deletion was detected in a father and son with
      clinical features of heterozygous FH. To our knowledge this is the first
      pathogenetic LDLR mutation identified in FH patients of Iranian-Armenian
      ancestry.

PMID- 8740920
TI  - Trisomy 18 mosaicism associated with secondary amenorrhea: ratios of mosaicism in
      different samples and complications.
AB  - A 28-year-old woman who complained of irregular menstruation was diagnosed as
      suffering from trisomy 18 mosaicism. She was karyotyped because of her
      characteristic face, mild mental retardation and aberrant hyperpigmentation of
      the skin. Her motor function was within normal range. Physical and laboratory
      examinations, however, revealed obesity, short stature, minor anomalies of the
      fingers, many areas of hyperpigmentation on the trunk and the hips,
      hypergonadotropinemia, diabetes mellitus, liver dysfunction, and hyperlipidemia.
      The ratios of normal/trisomy 18 were 4:135 in blood lymphocytes, 3:11 in a
      hyperpigmented area of the skin, 20:0 in a normally pigmented area of the skin,
      and 14:6 in ascitic cells. Laparoscopy revealed that her ovaries contained
      neither follicles nor germ cells.

PMID- 8740921
TI  - Determination of cystic fibrosis carrier frequency for Zuni native Americans of
      New Mexico.
AB  - The Zuni native Americans of the Southwest have an incidence of cystic fibrosis
      of approximately one in 333 or seven and one-half times that found for
      Caucasians. Earlier studies indicated that dF508 was not among the cystic
      fibrosis mutations causing this disease. Through a collaborative study the R1162X
      mutation was found on 12 out of 12 cystic fibrosis chromosomes from six Zuni
      patients. Because of the relative high incidence of cystic fibrosis, we undertook
      a study to determine the carrier frequency of the R1162X mutation among randomly
      sampled individuals. We found the carrier frequency in the general population for
      the R1162X to be 6.7%, a very significant number when compared with the carrier
      frequency for all cystic fibrosis mutations in the Caucasian population of
      approximately 4%.

PMID- 8740922
TI  - Microcephaly, seizures, genital hypoplasia, and abnormalities of the hands and
      feet in a 4-year-old boy with possible Wiedemann syndrome.
AB  - We report on a 4-year-old boy with short stature, microcephaly, BNS (Blitz-Nick
      Salaam) seizures, and global developmental delay. In addition, small and fleshy
      hands and feet as well as hypoplastic scrotum and testes were observed. The
      clinical features of the patient are compared with the patients previously
      described by Wiedemann et al. and Nevin et al. They reported three patients with
      a syndrome characterized by short stature, microcephaly, global developmental
      delay, abnormalities of hands and feet, seizures, large anterior fontanelle,
      scrotal hypoplasia, micropenis, cryptorchism, urinary tract abnormalities, and
      inguinal hernia (Wiedemann syndrome).

PMID- 8740923
TI  - Mild CF in a delta F508/R347H compound heterozygote woman: does the manifestation
      of this genotype differ in the two sexes?
AB  - A woman with unusually mild cystic fibrosis (CF) and normal sweat chloride levels
      is reported to have delta F508 deletion on one CF chromosome and the rare
      mutation R347H on the other, the first known female with this mutation. Of the
      other eight cases with R347H mutation mentioned in the literature, all five
      patients whose age and sex were given in the reports were men and had congenital
      bilateral absence of vas deferens (CBAVD). Considering these data, it is not
      unrealistic to assume that R347H associates more frequently than other CF
      mutations with CBAVD, which would mean that the clinical significance of this
      mutation might differ in males and females.

PMID- 8740924
TI  - Screening for coeliac disease as a possible maternal risk factor for neural tube
      defect.
AB  - Coeliac disease is an important cause of malabsorption, particularly of folic
      acid, in adults. We investigated the possibility that it might be a maternal risk
      factor for neural tube defect (NTD)-associated pregnancy by screening affected
      mothers using serum endomysial antibody (EmA) which has high sensitivity and
      specificity for coeliac disease. One (1.6%) of 60 patients was EmA positive and
      had a diagnosis of coeliac disease confirmed by the finding of villous atrophy on
      jejunal biopsy. In conclusion, the majority of NTD-associated pregnancies are not
      associated with maternal coeliac disease and our study is additional evidence
      that abnormalities of folic acid metabolism rather than absorption are the most
      important risk factors for NTD. Further studies are needed to determine whether
      the coeliac disease prevalence among women with NTD-affected pregnancy is higher
      than that of the general population.

PMID- 8740925
TI  - Myocardial contractile response and IP3, cAMP and cGMP interrelationships.
AB  - An experimental study in the perfused working normal and pressure overloaded rat
      heart. A mini review based on a doctoral thesis.

PMID- 8740926
TI  - Carbon dioxide formation and elimination in man. Recent theories and possible
      consequences.
AB  - Systemic metabolism results in a production of not only carbon dioxide, water and
      urea but also bicarbonate ions. Most of these bicarbonate ions are generated
      during the catabolism of glutamine. In order to be eliminated as carbon dioxide
      in the lungs bicarbonate ions must be protonised. This protonisation of the
      bicarbonate ion seems to take place in a number of tissue compartments in which
      acid-base balance is maintained. One of the most important processes for
      protonisation of the bicarbonate ion is the hepatic ureagenesis from
      ammonia/ammonium ions. A substantial part of the ammonia/ammonium ions are
      generated during the catabolism of amino acids. Terminal oxidation of glutamine
      in the gut seems to be of great significance for this process. In certain
      conditions the enteric generation of ammonium ions seems so important that an ATP
      driven enterohepatic recirculation of ammonium ions/urea constituting an
      amplifying mechanism for the protonisation of the bicarbonate ion is motivated.

PMID- 8740927
TI  - Diagnostic value of electron microscopy in rare malignant musculoskeletal tumors.
      Experience from an orthopedic tumor center.
AB  - Rare musculoskeletal tumors can be difficult to diagnose by light microscopy or
      immunohistochemistry. Electron microscopy can be of diagnostic assistance
      especially if histotype specific ultrastructural features exist. In particular,
      electron microscopy for uncommon sarcomas such as alveolar soft part sarcoma,
      parachordoma, atypical Ewing's sarcoma and epithelioid sarcoma may be the
      diagnostic modality of choice.

PMID- 8740928
TI  - Peptidergic innervation of the human gallbladder.
AB  - The human gallbladder was investigated by means of immunohistochemical methods
      for the occurrence of peptidergic nerve fibres. In the gallbladder 11 types of
      peptidergic nerve fibres were observed. These were somatostatin-, pancreatic
      polypeptide (PP)-, peptide YY (PYY)-, neuropeptide Y (NPY)-, vasoactive
      intestinal peptide (VIP)-, gastric inhibitory peptide (GIP)-, neurotensin-,
      cholecystokinin (CCK)/gastrin C-terminus, substance P-, galanin- and serotonin
      immunoreactive nerve fibres. NPY- and GIP-containing neurones were occasionally
      observed in the ganglionated plexus in the fibromuscular coat. Somatostatin-, NPY
      , neurotensin-, and galanin-immunoreactive nerve fibres were abundant. The other
      nerve fibres were few. Peptidergic nerve fibres occurred in the lamina propria
      mucosae around and in close contact with the basement membrane of the epithelial
      cells. In the fibromuscular coat, they lied mainly around the muscle bundles.
      They showed no special arrangement in the perimuscular connective tissue. In both
      arteries and veins somatostatin-, neurotensin, and galanin nerve fibres were
      detected in both tunica media and tunica adventitia. NPY-nerve fibres were found
      in tunica media and substance P- and GIP- nerve fibres in tunica adventitia. The
      peptidergic nerve fibres observed in the gallbladder outnumbered those observed
      with the peripheral nerve markers used in this study. It has been speculated that
      this might be due to the coexistence of several neuropeptides in the same nerve
      fibre and/or the coexistence of these neuropeptides with a classical
      neurotransmitter.

PMID- 8740929
TI  - Occurrence of adenylate kinase in cerebrospinal fluid after isoflurane
      anaesthesia and orthognathic surgery.
AB  - The study objective was, firstly, to investigate whether anaesthesia with induced
      arterial hypotension would cause leakage of a biochemical marker of neuronal
      injury, adenylate kinase (AK), into the cerebrospinal fluid (CSF). ( DEFINITION:
      arterial hypotension = mean arterial pressure (MAP) 50-65 mmHg during > or = 10
      min). Secondly, a subgroup of patients was examined with a limited battery of
      psychometric tests. Patients, scheduled for orthognathic surgery, were allocated
      to either hypotension (n = 20) or normotension (n = 20). Seventeen patients were
      subjected to psychometry. Arterial blood pressure was recorded continuously and
      controlled by adjustments of the administered concentration of the inhalational
      anaesthetic isoflurane. Fentanyl, an opioid, was given equally in both groups. A
      lumbar puncture was performed approximately 20 h post-operatively for a CSF
      sample, later analysed for AK activity. Neuropsychological tests were performed
      the day before surgery and the fourteenth day postoperatively. The CSF-AK value
      was pathologically increased ( > 0.040 U/L) in 24 patients (65%), of whom 9 were
      normotensive. There was no significant difference between the CSF-AK values in
      the hypotensive and normotensive groups, mean values were 0.082 (s.d. 0.051) and
      0.066 (s.d. 0.059) U/L, respectively. The overall correlation between the 10 min
      MAP levels and the CSF-AK values was close to zero. In the pilot
      neuropsychological investigation some abnormalities were observed, indicating
      clinically significant adverse effects in four hypotensive patients, of whom two
      displayed pathologically increased CSF-AK values. At the group level, the
      correlation between the changes in psychometry and the measured CSF-AK values was
      poor. Increases in CSF-AK activities may be a non-specific occurrence in the
      perioperative interval, possibly indicating an adverse effect on the brain.
      Arterial hypotension could not be proven to explain the CSF-AK outcome.

PMID- 8740930
TI  - A modified technique of ultrasonic triplex scanning of the lower extremity
      arteries.
AB  - This study was undertaken to evaluate the utility of a modified technique of
      triplex scanning of the lower extremity arteries in 20 subjects without any
      clinical signs of arterial disease. The distal aorta and iliac arteries were
      examined with the subject in supine position and lying slightly on the opposite
      side. By moderate compression of the probe towards the psoas muscle and directing
      it over the iliac arteries with slight medial retraction of the abdomen,
      satisfactory visualization of the common and external arteries with 7.5 MHz high
      resolution imaging and a 5.6 MHz doppler probe were obtained in 56 of 80 segments
      (70%). In obese individuals it was necessary to use 5 MHz probe for satisfactory
      scanning of the aortic bifurcation and common iliac arteries. The distal
      superficial femoral, popliteal and tibioperoneal trunk segments were examined
      with the patient prone and the knee slightly flexed. Peak systolic, early
      diastolic reverse and late diastolic forward flow velocities were studied
      together with measurement of the arterial diemeters, which demonstrated wide
      variations. This study suggests that satisfactory scanning of the iliac and
      femoropopliteal arteries with the described technique can be achieved in the
      majority of subjects with a superficial high resolution probe. The combination of
      7.5 MHz two-dimensional imaging with a 5.6 MHz pulsed wave Doppler probe offers
      optimal information of these arteries in nonobese individuals.

PMID- 8740931
TI  - New therapeutic agents for the treatment of NIDDM.
AB  - Non-insulin dependent diabetes mellitus (NIDDM) is a heterogeneous disease with a
      world wide growing prevalence. Insulin resistance, particularly an impaired
      action of insulin on the glucose metabolism in skeletal muscles, has been assumed
      to be the primary factor in the pathophysiology of this disease and it is
      observed years before the precipitation of overt NIDDM. Almost half of the
      patient population already suffer from macroangiopathy at the time of diagnosis
      and the overall mortality rate primarily due to coronary heart disease is
      approximately 2.5 times higher as compared with healthy individuals. It can be
      assumed that these complications are closely linked to insulin resistance and a
      result of the "metabolic syndrome". Insulin resistance is obviously a strong
      predictive factor for NIDDM, but it is not sufficient for the development of
      overt diabetes. For the precipitation of overt NIDDM an impaired function of the
      pancreatic B-cells is also required which seems to be a consequence of the
      excessive demand for insulin in insulin resistant individuals. Increasing
      knowledge about the pathophysiology of type II diabetes led to completely new
      approaches for the treatment of this disease. In this context compounds
      exhibiting an effect on the peripheral insulin resistance are of special interest
      and the promising results of clinical trials with troglitazone, a
      thiazolidinedione derivative, can be regarded as a proof of this newly discovered
      therapeutic concept. Since the primary effect of this compound is to improve the
      response of peripheral target tissues to insulin, this should result in a better
      glycemic control and a concomitant decrease of the circulating insulin levels.
      Although troglitazone can be regarded as a first approach to a new therapeutic
      regimen, we are only at the beginning of a new and very exciting area. Future
      research efforts should be focussed on the discovery of therapeutic agents with
      higher potency and the fact that not all patients can be treated with
      troglitazone (non-responder) leads to the assumption that different patient
      populations may require different therapeutic agents. The effect of insulin
      sensitizers on insulin resistance and hyperinsulinemia may be of important
      consequence since insulin resistance has been linked to an increased risk of
      coronary artery disease as a major cause of mortality in NIDDMs.

PMID- 8740932
TI  - Observations on the decay of glycated hemoglobin HbA1c in diabetic patients.
AB  - In 44 diabetic patients, who within 7 days lowered their average glycemia by 140
      to 220 mg % and kept it at this level over a mean of 36 days, HbA1c was measured
      repeatedly by HPLC (normal range 4.2-5.6% of total hemoglobin). Thereby, the
      maximum decay rate of HbA1c could be observed in vivo as being 0.1% per day which
      is consistent with previous theoretical considerations by other authors. Some
      clinical implications that this finding may have for diabetic patients are being
      discussed.

PMID- 8740933
TI  - Prevalence of lipohypertrophy in insulin-treated diabetic patients and
      predisposing factors.
AB  - In a cross-sectional study the frequency of insulin-induced lipohypertrophy at
      injection sites was assessed in 223 type 1 and 56 type 2 diabetic patients. 64
      (28.7%) of the subjects with type 1 diabetes, but only 2 (3.6%) of those with
      type 2 diabetes presented clinical evidence of lipohypertrophy. In every second
      affected type 1 diabetic patient lipohypertrophy developed within 2 years after
      starting insulin therapy. The occurrence of lipohypertrophy was independent of
      the insulin source and mode of therapy. In a multivariate logistic regression
      analysis young age, low body mass index, abdominal injection site and,
      particularly, missing rotation of injection site were significant independent
      risk factors for the presence of insulin-induced lipohypertrophy. Avoidance of
      such areas led to a partial or full remission of tissue swellings in 6 of 11
      cases under observation for one year. In conclusion, lipohypertrophy is still a
      frequent complication of insulin therapy. To prevent such local skin reactions
      insulin-treated patients should be more intensively trained to regularly change
      injection sites.

PMID- 8740934
TI  - Expression of estrogen receptor and proto-oncogene messenger ribonucleic acids in
      reproductive tracts of neonatally diethylstilbestrol-exposed female mice with or
      without post-puberal estrogen administration.
AB  - Perinatal treatment of female mice with natural and synthetic estrogens including
      diethylstilbestrol (DES) results in estrogen-independent persistent proliferation
      and cornification of the vaginal epithelium. The dynamics of the induction of
      estrogen receptor (ER), c-jun, c-fos and c-myc mRNAs by 17 beta-estradiol (E2)
      was examined in the uterus and vagina of neonatally DES-exposed and -unexposed
      ovariectomized adult mice. In the uterus of neonatally DES-unexposed
      ovariectomized mice, the expression of ER mRNA increased within 1 h after E2
      administration and declined by 12 h thereafter. ER mRNA in the vagina decreased
      within 1 h after the stimulation and recovered by 12 h thereafter. In the uterus,
      c-jun and c-fos mRNAs increased in concentration within 1 h after E2
      administration, showing a peak 3 h after the stimulation; they decreased with
      time thereafter. In the vagina, the concentration of c-jun and c-fos mRNAs
      increased rapidly, reaching a peak within 1 h after the stimulation. However, the
      expression of c-myc in uterus and vagina was not changed by postpuberal E2. These
      results suggest that estrogen regulation of ER and proto-oncogene mRNAs in the
      vagina differs from those in the uterus. In the neonatally DES-exposed
      ovariectomized adult mice, uterine ER mRNA expression levels were significantly
      higher than in the unexposed ovariectomized controls; however, vaginal levels
      were drastically lower than in the controls. Expression of c-jun and c-fos mRNAs
      was greater in both the uterus (3- and 6-fold, respectively) and the vagina (18-
      and 4-fold) of neonatally DES-exposed mice than in controls. The ER mRNA and the
      increased levels of c-fos and c-jun mRNAs in both uterus and vagina of neonatally
      DES-exposed ovariectomized mice were not further altered by post-puberal E2 and
      may be related to ovary-independent persistent changes in the genital tract.

PMID- 8740935
TI  - Are serum neopterin concentrations superior to other parameters in the
      differential diagnosis and prognostic assessment of Graves' disease?
AB  - There is a lack (1.) of a single criterion for the definitive differentiation
      between immunogenic (IH) and non-immunogenic hyperthyroidism (NIH), and (2.) also
      a lack of an unequivocal prognostic predictor for the individual course of
      patients with immunogenic hyperthyroidism. In 152 patients scheduled for iodine
      131 therapy, serum neopterin concentrations were measured using a commercially
      available RIA, and the neopterin concentrations of IH (n = 84) and NIH (n = 42)
      patients were compared. Of these patients, 83 and 26 per cent respectively were
      treated with antithyroid drugs which did not have a significant impact on
      neopterin levels. In patients with IH and NIH, the concentrations [mean +/- SD]
      of neopterin were 1.89 +/- 0.79 milligrams and 1.98 +/- 0.9 milligrams,
      respectively (p = 0.4). After therapy with iodine-131, 28% of the IH-patients
      were euthyroid, 32% hyperthyroid, and 40% hypothyroid. In finally euthyroid
      patients, pretherapeutic neopterin concentrations were higher (3.1 +/- 2.8
      milligrams) than in finally hyperthyroid (1.8 +/- 0.7 milligrams), or hypothyroid
      (1.6 +/- 0.7 milligrams) patients. These results argue against a relevant
      clinical role of neopterin concentrations for the differential diagnosis of IH
      versus NIH in these patients. However, a prognostic significance of neopterin
      concentrations in patients with IH is suggested.

PMID- 8740936
TI  - Relationship between sex steroid hormone levels and CD4 lymphocytes in HIV
      infected men.
AB  - The serum concentrations of the steroid, androgens and estrogens, in the HIV
      positive male patients were studied. These men belonged to one of the three main
      behaviour groups: heterosexual (He), drug addicts (DA) and homosexual (Ho) at
      early stages (II and III) or at advanced stage of AIDS (IVC), classified
      according to the Centers for Disease Control (CDC). The circulating
      concentrations of sex steroids were then analysed with reference to the risk
      factors, absolute CD4 cell count and the progression of HIV infection. Regardless
      of risk factors, the stage II and III HIV-infected patients had serum dehydro
      epiandrosterone sulfate (DHEAs) (+37%, p < 0.03), testosterone (T) (+24%, p <
      0.006) and estrone (E1) (+170%, p < 0.0001) levels higher than those of controls.
      The patients IVC stage had low serum DHEAs (-48%, p < 0.0001) and elevated
      estradiol (E2) (+200%, p < 0.0001). According to risk factors, there were no
      significant differences in androgen and estrogen concentrations between the
      behaviour groups. There were significant positive correlations between the CD4
      cell count and the serum concentrations of DHEAs (p < 0.0001), DHEA (p < 0.01)
      and E1 (p < 0.006). This suggests that there is a relationship between the
      circulating sex hormone levels, particularly DHEAs, and the progression of immune
      depression in HIV, whatever the risk factor. The observed association between
      DHEAs and the progression of HIV infection suggests that this androgen may play a
      role in the normal function of the immune system.

PMID- 8740937
TI  - Regulation of bile acid synthesis by estradiol and progesterone in primary
      cultures of rat hepatocytes.
AB  - We have used primary monolayer cultures of hepatocytes from rats fed standard and
      cholestyramine-diet to study the effects of 17 beta-estradiol and progesterone on
      the activity of cholesterol 7 alpha-hydroxylase (EC 1.14.13.17) and bile acid
      synthesis. Cholesterol 7 alpha-hydroxylase activity in hepatocytes freshly
      isolated from rats fed either diet mentioned above declined gradually during
      attachment and the first day of culture. Exposure of cell monolayers to 1 or 10
      microM estradiol or progesterone resulted in rapid and transient increases in
      cholesterol 7 alpha-hydroxylase activity, the maximal stimulation of enzyme
      activity being observed after a 6 h culture period. Bile acid synthesis in
      standard cells was markedly activated by both hormones, but in cholestyramine
      cells only the effect caused by 10 microM progesterone was significant. The
      cellular content of total bile acids was not significantly altered by the
      presence of the hormones, except by 10 microM progesterone, which provoked an
      initial cellular depletion of bile acids that was rapidly restored. Bile acid
      output was enhanced by treating primary cultures with 10 microM estradiol or
      progesterone, but whereas the increases caused by progesterone were marked and
      sustained, those caused by estradiol were minor and transient. We conclude that
      progesterone and 17 beta-estradiol, in this order of potency, enhance short-term
      bile acid synthesis in rat hepatocyte monolayers.

PMID- 8740938
TI  - Differences in the nyctohemeral secretion of TSH and PRL in healthy euthyroid
      men.
AB  - The circadian rhythm of TSH, PRL and cortisol was studied in 21 healthy euthyroid
      men in a normal sleep/wake cycle. Higher nyctohemeral (22.00 h till 6.00 h)
      levels of TSH as compared to diurnal (8.00 h till 22.00 h) levels were observed
      in 14 out of 21 men (Group A). In the remaining 7 volunteers the nyctohemeral and
      diurnal TSH-levels (Group B) were the same. In Group A, the nyctohemeral PRL
      surge was also higher than in Group B (p < 0.01). The nyctohemeral area under the
      curve (AUC) of both TSH and PRL were significantly higher in Group A than in
      Group B (p < 0.05 and p < 0.001 respectively). The mean diurnal concentrations of
      TSH and PRL were, however, similar in both groups. Therefore, an impairment of
      the nyctohemeral TSH-surge can occur in healthy men usually combined with a
      reduced nyctohemeral PRL-surge. An impairment of nyctohemeral TSH-surge is thus
      not confined to patients with thyroid diseases.

PMID- 8740939
TI  - Drug effects on triiodothyronine uptake by rat anterior pituitary cells in vitro.
AB  - In nonthyroidal illness, numerous drugs such as glucocorticoids, dopamine,
      fenclofenac, furosemide and diphenylhydantoin may modify the close inverse
      feedback relationship between circulating thyroid hormones and TSH. Such effects
      could involve altered hypothalamic TRH secretion, a direct effect on TSH
      production by the thyrotroph, alterations in circulating free thyroid hormone
      concentrations, or changes in thyroid hormone uptake by the thyrotroph. We
      therefore examined the effect of nonsteroidal antiinflammatory drugs (NSAID),
      diuretics, the synthetic flavonoid EMD 21388, and diphenylhydantoin, on [125I]T3
      cellular uptake in rat pituitary primary cell cultures. Uptake of [125I]T3 (cell
      associated counts of washed cells) was measured at 15 min after the addition of
      50 pmol/L [125I]T3 in protein-free medium (37 degrees C, pH 7.4). Uptake of
      [125I]T3 by pituitary cells was 6.0 +/- 1.7% of total counts (mean +/- SD, n =
      18). Unlabeled T3 (10 mumols/L) displaced 92% of total uptake. The IC50 of
      unlabeled T3 for the displacement of [125I]T3 was 1.2 mumols/L. T4 and rT3 were
      approximately 10% as effective as T3 itself in inhibiting [125I]T3 uptake, while
      triac did not affect cellular [125I]T3 uptake. Inhibition of [125I]T3 uptake at
      drug concentrations of 100 mumols/L was seen with the diuretics, furosemide (9%),
      bumetanide (14%), piretanide (12%) and ethacrynic acid (76%), the NSAID,
      meclofenamic acid (35%) and fenclofenac (52%), EMD 21388 (49%), and the
      anticonvulsant, diphenylhydantoin (23%). Aspirin, up to 500 mumols/L, had no
      effect on [125I]T3 uptake. Our results indicate that ethacrynic acid,
      meclofenamic acid, fenclofenac, EMD 21388 and diphenylhydantoin affect plasma
      membrane T3 uptake in the pituitary. This potential influence on TSH release will
      be contrary to the previously-demonstrated direct inhibitory effect of these
      drugs on TSH release.

PMID- 8740940
TI  - Effect of human chorionic gonadotropin on uterine blood flow in intact and
      ovariectomized gilts.
AB  - This experiment was designed to test the hypothesis that human chorionic
      gonadotropin (hCG) can directly influence uterine blood flow in pigs. In the
      study, 18 crossbred gilts (95-100 kg) which had exhibited at least one estrous
      cycle were used: 8 cyclic gilts in the luteal phase of the estrous cycle and 10
      gilts ovariectomized (OVX) three weeks before the experiment began. The OVX
      animals received i.m. injections of 1 mg estradiol benzoate and 50 mg
      progesterone daily for five consecutive days before transducer implantation.
      Precalibrated electromagnetic blood flow transducers were surgically implanted
      around the uterine artery under general anaesthesia. Beginning at 120 min (0 h)
      following the placement of probes, i.e. after recording had stabilized, blood
      flow values were recorded at 10 min intervals for the next 360 min. At 0 h,
      cyclic (n = 4) and OVX (n = 5) gilts received a bolus injection (5 ml) of 1000 IU
      hCG intravenously through an indwelling catheter and then the same dose of hCG
      continuously during 4 hours in 40 ml of saline. The remaining cyclic (n = 4) and
      OVX (n = 5) gilts were infused with saline only and served as control. The mean
      (SEM) uterine blood flow at 0 h in cyclic (n = 8) and OVX (n = 10) gilts was
      104.0 +/- 25.7 and 58.6 +/- 6.0 ml/min, respectively. Because of the variability
      of initial blood flow, especially in the cyclic gilts, hCG induced changes were
      expressed as a percent change from the initial flow and were compared to
      pretreatment period 0 (-30 - 0 h). hCG produced a significant increase in the
      uterine blood flow in both treated groups (p < 0.05) reaching at 70 min 110.2 +/-
      3.4 vs 80.0 +/- 10.5 and 122.4 +/- 12.1 vs 90.6 +/- 3.8, and then at 230 min
      116.7 +/- 9.3 vs 62.0 +/- 10.0 and 121.8 +/- 13.2 vs 85.4 +/- 2.3 percent of
      initial blood flow in cyclic and OVX gilts, respectively. A comparison of nine 30
      min periods (periods 1-9) to period 0 showed a significant decrease of uterine
      blood flow in both (cyclic and ovariectomized) saline control groups in periods 2
      9 (50-360 min). The comparison of the same periods in cyclic and ovariectomized
      hCG treated gilts revealed a significant increase during periods 7-9 (250-360
      min) and in period 6, 9 (210-240 and 330-360 min), respectively. Serum estradiol
      levels increased significantly from 7.4 +/- 1.5 to 351.9 +/- 50.2 pg/ml in
      cyclic, and from 43.3 0 +/- 7.0 to 224.8 +/- 24.1 in OVX hCG treated gilts at 180
      and 120 min, respectively, and returned to the levels of the control groups 240
      300 min after the beginning of hCG infusion. Those results indicate that the
      early response in uterine blood flow is produced directly by hCG, which overcomes
      the inhibitory pharmacological effect of pentobarbital on uterine blood flow. The
      second phase of response to hCG could be caused by estradiol which significantly
      increased an hour earlier before uterine blood flow elevation. We have also shown
      a novel source of estradiol in castrated pigs which is released by hCG.

PMID- 8740941
TI  - Cholecystokinin octapeptide and the daily rhythm of vasopressin and oxytocin
      release.
AB  - The daily rhythm of neurohypophysial hormone release was monitored in rats given
      intracerebroventricularly (i.c.v.) CCK-8 (50 ng/10 microliters--once daily over
      five days). In animals injected i.c.v. with vehicle solution (0.9% NaCl) plasma
      oxytocin and vasopressin concentrations were seen to rise significantly over the
      hours of daylight, decreasing during the night. The changes seen in the
      neurohypophysial vasopressin and oxytocin content were inversely related to the
      plasma concentrations. Under i.c.v. treatment with CCK-8, the daily rhythm of the
      vasopressin and oxytocin release was similar to daily rhythm in the control
      group; respective figures were, however, reduced for the hypothalamus and
      neurohypophysis as well as increased for the blood plasma. It is suggested that
      CCK-8 may be involved in some circadian regulatory processes related to
      vasopressin and oxytocin release from the rat hypothalamo-neurohypophysial
      system.

PMID- 8740942
TI  - Parameters of respiratory burst and arachidonic acid metabolism in
      polymorphonuclear granulocytes from patients with various thyroid diseases.
AB  - The oxidative processes (oxygen consumption, superoxoid anion generation,
      arachidonic acid cascade) of human polymorphonuclear granulocytes (PMNs) obtained
      from patients suffering from thyroid disorders of autoimmune origin (Graves'
      disease and Hashimoto's thyroiditis), and non autoimmune origin (toxic adenoma)
      were investigated. All Graves' and toxic adenoma patients were hyperthyroid.
      Hashimoto's thyroiditis patients were euthyroid. Healthy age and sex matched
      volunteers served as controls. The results are as follows: 1) In PMNs from both
      hyperthyroid groups (Graves' disease and toxic adenoma), independently from the
      autoimmune origin of the disease, a significantly increased Antimycin A sensitive
      mitochondrial oxygen consumption and a slightly increased superoxide anion
      generation were detected. 2) In both autoimmune thyroid disease groups (Graves'
      disease and Hashimoto's thyroiditis)--depending on the functional state of the
      thyroid gland--a significantly altered intracellular killing activity was
      measured. 3) An increased arachidonic acid cascade--triggered by opsonized
      zymozan (OZ)--was detected in both autoimmune thyroid diseases. The increased
      arachidonic acid cascade was sensitive to phospholipase A2 inhibiting Mepacrin
      treatment. 4) The PMNs from both autoimmune thyroid diseases produced large
      amount of leukotriens (LTs)--LTC4 and LTB4--after stimulation through their Fc
      receptors but the synthesis of prostagalandins (PGs) has not changed. There are
      no data indicating local, specific effects of circulating leukotriens in the
      thyroid gland itself, but based on authors' data, their general, regulating role
      on both the endocrine-- as well as on the immune system--seems to be plausible.

PMID- 8740943
TI  - Lack of islet amyloid polypeptide/amylin-immunoreactivity in urine collected from
      healthy volunteers after ingestion of a carbohydrate-rich meal.
AB  - Islet amyloid polypeptide (IAPP), or amylin, is synthesized by beta cells in the
      islets of Langerhans of the pancreas. Plasma IAPP levels are highly elevated in
      patients with advanced renal failure. To investigate the involvement of the
      kidney in the clearance of IAPP, the response of plasma and urinary IAPP to a
      carbohydrate-rich meal was investigated in 14 healthy volunteers. Although plasma
      IAPP levels increased severalfold after the meal, no IAPP-immunoreactivity was
      detected in the urine samples up to 4 hours after the meal. This might be due to
      the fact that urinary IAPP levels are under the detection limit of the assay or,
      assuming the presence of IAPP in the primary urine, immunoreactive IAPP molecules
      may be processed by renal mechanisms in such a way that they are no longer
      recognized by the antibodies used in the radioimmunoassay. Processed IAPP
      molecules may be reabsorbed in the proximal tubules of the kidney and/or
      excreted.

PMID- 8740944
TI  - Chronic intestinal giardiasis with isolated levothyroxine malabsorption as reason
      for severe hypothyroidism--implications for localization of thyroid hormone
      absorption in the gut.
AB  - We report a case of isolated levothyroxine malabsorption in the course of chronic
      intestinal giardiasis, leading to severe hypothyroidism. Infection with Giardia
      lamblia was proved histologically by jejunal biopsy. Treatment with metronidazole
      resulted in complete elimination of parasites and recovery of regular intestinal
      thyroid hormone absorption. Stable euthyroidism was accomplished with common
      replacement doses of orally administered levothyroxine.

PMID- 8740945
TI  - Cell tropism of the simian foamy virus type 1 (SFV-1).
AB  - Several cell lines representing different species and cell types were tested for
      simian foamy virus type 1 (SFV-1) infection. SFV-1 infections were monitored by
      polymerase chain reaction, reverse transcriptase, cytopathology, and
      immunofluorescent assays. All cells tested were permissive for SFV-1,
      demonstrating that SFV-1 has a broad host range with respect to species and cell
      types. Infected fibroblasts, epithelial cells, and neural cells all showed
      extensive cytopathology that is characteristic of foamy virus infection. No
      cytopathology was induced in T cell-derived Jurkats and Hut-78 cell lines. The
      cytopathic effects in B and macrophage originated cells were delayed by several
      days. Cytopathology in these cell lines was not as dramatic as seen in the
      infected fibroblast and epithelial cells. The reverse transcriptase values in the
      SFV-1 infected lymphoid and macrophage cell lines were severalfold lower than
      that of the fibroblasts and epithelial cells. Therefore, SFV-1 appears to
      establish a low level persistent infection in lymphoid and macrophage cell lines.

PMID- 8740946
TI  - Leukocyte trafficking in free-flowing cerebrospinal fluid of normal rhesus
      macaques (Macaca mulatta).
AB  - Cellular components in free-flowing cerebrospinal fluid (CSF) of normal rhesus
      macaques were characterized. Microscopic counting enumerated the total number of
      leukocytes, percentage of polymorphonuclear cells (PMN), leukocytes with
      nonspecific esterase (NSE), and those reducing nitro blue tetrazolium (NBT). Flow
      cytometric analysis further identified CD4, CD8, CD14, and CD20 positive
      leukocytes. These experiments established reliable techniques for evaluating
      cellular components in CSF from rhesus macaques and documented the difference in
      the CD4/CD8 ratio between peripheral blood (PB) and CSF compartments under normal
      physiological conditions.

PMID- 8740947
TI  - Subcutaneous rabies vaccination of pigtail macaques.
AB  - Nonhuman primates housed in outside cages in rabies enzootic areas should be
      vaccinated against rabies because of the risk of exposure to rabid wildlife. This
      article reports that vaccination with an inactivated rabies vaccine for domestic
      animals induced levels of neutralizing antibodies against rabies in pigtail
      macaques (Macaca nemestrina) without causing adverse reactions.

PMID- 8740948
TI  - Lipoprotein profiles and glucose tolerance in lean and obese chimpanzees.
AB  - We compared serum lipid profiles and glucose tolerance of obese and lean
      chimpanzees maintained on a 10.9% fat diet. Seven of 14 obese and 6 of 17 lean
      chimpanzees were hypercholesterolemic (low density lipoprotein cholesterol > 160
      mg/dl), three obese and three lean animals had total cholesterol/high density
      lipoprotein cholesterol ratios of 5.9-10.7, and two obese and one lean chimpanzee
      had abnormal glucose tolerance. Useful numbers of captive chimpanzees thus
      exhibit metabolic abnormalities without recourse to high fat diets and could
      serve as surrogates in studies of human metabolic diseases.

PMID- 8740949
TI  - Influences of blood sampling procedures on basal hypothalamic-pituitary-adrenal
      hormone levels and leukocyte values in rhesus macaques (Macaca mulatta).
AB  - The influences of housing location and temporal factors on the results of blood
      sampling were examined to determine their contributions to levels of hypothalamic
      pituitary-adrenal hormones, as well as leukocyte subset counts from peripheral
      blood in rhesus monkeys. Differences in housing location and the amount of room
      disturbance associated with blood sampling have a significant impact on cell
      counts, but not on ACTH or cortisol levels.

PMID- 8740950
TI  - Endocrine neoplasia in New World primates.
AB  - Of 1,106 New World primates necropsied from the National Zoological Park
      (Washington, D.C.) and the Department of Comparative Pathology, Johns Hopkins
      University School of Medicine (Baltimore, Maryland) 22 (1.9%) animals were
      identified with 27 neoplasms. Of this group, nine animals (two females, seven
      males) had a total of 13 endocrine neoplasms. All animals were adults, with an
      age range of 2.7-25 years (average, 12.1 years). Seven were Callitrichidae and
      two were Cebidae. The adrenal gland was the most affected organ, with seven
      (53.8%) neoplasms, followed by the pituitary and thyroid gland with two (15.4%)
      cases each, and the pancreas and parathyroid gland with one tumor (7.7%) each.
      All neoplastic disorders were benign. Immunocytochemistry assays for growth
      hormone, adrenocorticotropic hormone, prolactin, follicle-stimulating hormone,
      luteinizing hormone, thyroid-stimulating hormone, and chromogranin A were
      performed on two pituitary neoplasms. Pheochromocytoma was the most frequent
      neoplasm, representing 5 (38.4%) of the 13 neoplasms. The remaining were thyroid
      cystadenoma (two, 15.4%), corticotrophic cell pituitary adenoma (two, 15.4%),
      adrenal ganglioneuroma (one, 7.7%), adrenal cortical adenoma (one, 7.7%),
      parathyroid chief-cell adenoma (one, 7.7%), and pancreatic islet-cell adenoma
      (one, 7.7%).

PMID- 8740951
TI  - Antibody responses to two encephalomyocarditis virus vaccines in rhesus macaques
      (Macaca mulatta).
AB  - Two groups of rhesus macaques (Macaca mulatta) housed in rodent-controlled
      outdoor corrals were inoculated with two different encephalomyocarditis virus
      (EMCV) vaccines. One group (n = 45) received a vaccine made from an inactivated
      field isolate of virus cultured during an outbreak at a zoo in Florida. This
      vaccine produced fourfold increases in the titers of 28 animals (62%); the
      increases persisted for at least 18 months (last test) after a single injection
      of the vaccine. The other group (n = 51) received a vaccine made from an
      inactivated porcine field strain of the virus. This vaccine did not produce
      titers in any of the vaccinees.

PMID- 8740952
TI  - Serum and urine biochemical diversity among adult wild-caught Aotus nancymae and
      Saimiri peruviensis.
AB  - Serum and urine analytes were compared between adult wild-caught owl monkeys
      (Aotus nancymae) and adult wild-caught squirrel monkeys (Saimiri peruviensis) to
      determine if normative clinical pathology data were similar. An objective of the
      study was to confirm that species of neotropical primates are distinct with
      regard to physiologic parameters, and should not be considered interchangeable in
      biomedical research. Significant differences (P < 0.05) were noted in many serum
      and urine analytes between the two groups. The results suggest that reference
      data for wild-caught owl monkeys are not applicable to squirrel monkeys, and the
      differences are sufficiently large to be of clinical significance. These findings
      illuminate the diversity among species of neotropical primates.

PMID- 8740953
TI  - Characterization of centchroman binding protein in plasma of rhesus monkey
      (Macaca mulatta).
AB  - Centchroman, a nonsteroidal antifertility agent was studied for its binding to
      monkey (Macaca mulatta) plasma proteins using charcoal adsorption and
      electrophoretic techniques. 14C-centchroman showed a low affinity binding and did
      not compete for 3H-cortisol or 3H-DHT binding sites in plasma. 14C-centchroman
      binding protein was heat stable in nature and showed the electrophoretic pattern
      similar to that of albumin (Rf 0.70). Thus centchroman binds to albumin in monkey
      plasma which can be suggested as carrier protein for this contraceptive agent.

PMID- 8740954
TI  - Patterns of prenatal survival in the common marmoset (Callithrix jacchus).
AB  - Fifty common marmoset pregnancies were monitored using ultrasound. The objective
      was to ascertain if fetal mortality was related to litter size. Prior to analysis
      we determined abortion rate and litter size were not influenced by repeated
      ultrasound. Mortality was unrelated to litter size and occurred fairly late in
      gestation. All singletons born in this study began gestation as twins. It is
      hypothesized that marmosets may be able to adjust litter size late in pregnancy
      in response to proximate environmental factors.

PMID- 8740955
TI  - A mobile cage facilitates periodic social contact and exercise for singly caged
      adult Vervet monkeys.
AB  - A mobile exercise cage that expands the quantity and improves the quality of the
      space available to singly caged adult Vervet monkey males is described. It was
      easily fitted into an existing caging system and the addition of a resident
      consort female made it possible for the males to mate and have regular social
      contact.

PMID- 8740956
TI  - Is there an epidemic/epizootic of spondyloarthropathy in baboons?

PMID- 8740957
TI  - Evil Spirit Sickness, the Christian disease: the innovation of a new syndrome of
      mental derangement and redemption in Papua New Guinea.
AB  - This essay analyses the cultural and historical processes involved in the
      emergence of Evil Spirit Sickness, a form of mental or behavioral derangement
      that appeared among the Bosavi people of Papua New Guinea during a period of
      intense Christian evangelization and religious excitement. It explores the
      emergence of the disorder both as a form of psychological breakdown under the
      burden of intolerable life stress and a socially innovated, ritually structured,
      and performatively achieved mode of seeking redemption in a Papuan Christian
      context.

PMID- 8740958
TI  - The definition and classification of Koro.
AB  - Attempts at defining and classifying Koro have been undertaken by various
      researchers over at least the last fifty years without any consensus emerging to
      date. The occurrence of Koro, not only in different parts of the world but also
      in association with varied morbidities, has of late diluted its primary identity
      as a culture-bound syndrome. Further, the DSM-IIIR and ICD-10 provisions to
      include culture-bound syndromes like Koro are open to various diagnostic options.
      Consideration was given to have it included in DSM-IV. One of the fundamental
      problems inherent in such attempts is the semantic confusion Koro generates in
      its basic phenomenological analysis. The present paper deals with some of these
      issues based on historical analysis of world Koro literature, and with comments
      on the future research agendum.

PMID- 8740959
TI  - A critical review of Chinese Koro.
AB  - Koro is generally considered a culture-bound psychiatric syndrome, the dominant
      feature of which is anxiety or dissociation. A close examination of koro
      epidemics in China, where koro cases appear to be more frequent than other parts
      of the world, shows that koro has a sociocultural component which has not been
      sufficiently taken into account in previous formulations. This article analyzes
      koro in the natural environment in which it appears and dispels the notion of
      koro being individual psychopathology. Koro, at least the way it is manifested in
      China, is a social malady maintained by cultural beliefs which affect the whole
      community and not just those diagnosed with it. Further directions for research
      into the subject are discussed.

PMID- 8740960
TI  - The cosmobiological balance of the emotional and spiritual worlds:
      phenomenological structuralism in traditional Chinese medical thought.
AB  - This paper points to a convergence of formal and rhetorical features in ancient
      Chinese cosmobiological theory, within which is developed a view of the inner
      life of human emotions. Inasmuch as there is an extensive classical tradition
      considering the emotions in conjunction with music, one can justify a structural
      analysis of medical texts treating disorder in emotional life, since emotions,
      musical interpretation and structural analysis all deal with systems interrelated
      in a transformational space largely independent of objective reference and
      propositional coordination. Following a section of ethnolinguistic sketches to
      provide grounds in some phenomenological worlds recognized by Chinese people,
      there is a textual analysis of a classical medical source for the treatment of
      emotional distress. Through close examination of the compositional schema of this
      text, it can be demonstrated that the standard categories of correlative
      cosmology are arrayed within a more comprehensive structural order.

PMID- 8740961
TI  - Probing the functional conformation of the tridecapeptide mating pheromone of
      Saccharomyces cerevisiae through study of disulfide-constrained analogs.
AB  - Analogs of the Saccharomyces cerevisiae alpha-mating factor, Trp-His-Trp-Leu-Gln
      Leu-Lys-Pro-Gly-Gln-Pro-Met-Tyr, where Lys7 and Gln10 were replaced with Cys,
      Cys(CH3), or Ser, were synthesized using solid-phase procedures on a
      phenylacetamidomethyl resin. Cyclo7,10[Cys7,X9,Cys10,Nle12]alpha-factor , where
      X=D-Val, D-Ala, L-Ala and Gly, were prepared by on-resin cyclization using
      thallic trifluoroacetate in yields of 20-30%. Linear sulfhydryl-containing
      peptides were generated from their corresponding cyclic peptide by treatment with
      dithioerythritol in basic solution. In the linear analogs, replacement of both
      Lys7 and Gln10 with a cysteine residue resulted in an over 100-fold loss of the
      biological activity when compared with the native pheromone. The corresponding
      cyclic disulfides were 5-10-fold more active than their sulfhydryl-containing
      homologs, and cyclo7,10[Cys7,L-Ala9,Cys10,Nle12] alpha-factor was 50-fold more
      potent than linear analogs containing Ser or Cys(CH3) in positions 7 and 10.
      Binding competition studies indicated that all analogs had low affinity for the
      alpha-factor receptor and there was a poor correlation between binding and
      activity in a growth arrest assay. A cyclic analog in which residues 8 and 9 were
      replaced by 5-aminopentanoic acid was not biologically active. Based on NMR
      studies, all cyclic peptides have a higher tendency to form beta-turns spanning
      residues 7-10 than their less active linear counterparts. The results provide
      strong evidence that this beta-turn is important for optimal signal transduction
      by alpha-factor.

PMID- 8740962
TI  - A pseudopeptide incorporating the tetrahydrophthalazine nucleus, a constrained
      aza analog of phenylalanine.
AB  - Replacement of the alpha-carbon with a nitrogen in alpha-amino acids gives rise
      to azaamino acids. Most examples of azaamino acids that have been incorporated
      into peptides are linear analogs, in which conformational effects are restricted
      to the immediate vicinity of the urea bond. In contrast to the linear azaamino
      acids, the heterocyclic analogs might be expected to exhibit stronger
      conformational preferences, but examples of this class of azaamino acids are very
      limited. We synthesized tetrahydrophthalazine (THPhth) as a constrained
      phenylalanine analog and elaborated it into the model pseudotripeptide N-?([N
      alanyl]-1,2,3,4-tetrahydro-2-phthalazinyl)carbonyl)?-L-alan ine (1). As shown by
      NMR studies, tetrahydrophthalazine 1A has a secondary structure in which psi
      THphth is fixed at 16-18 degrees and there are two equal populations of cis and
      trans amide bonds from the N-terminal alanine.

PMID- 8740963
TI  - Synthesis of the very acid-sensitive Fmoc-Cys(Mmt)-OH and its application in
      solid-phase peptide synthesis.
AB  - S-4-methoxytrityl cysteine was synthesized and converted into the corresponding
      Fmoc-Cys(Mmt)-OH by its reaction with Fmoc-OSu. As compared to the corresponding
      Fmoc-Cys(Trt)-OH, the S-Mmt-function was found to be considerably more acid
      labile. Quantitative S-Mmt-removal occurs selectively in the presence of groups
      of the tert butyl type and S-Trt by treatment with 0.5-1.0% TFA. The new
      derivative was successfully utilized in the SPPS of Tyr1-somatostatin on 2
      chlorotrityl resin. In this synthesis groups of the Trt-type were exclusively
      used for amino acid side-chain protection. Quantitative cleavage from the resin
      and complete deprotection was performed by treatment with 3% TFA in DCM-TES
      (95:5) for 30 min at RT. We observed no reduction of tryptophan under these
      conditions.

PMID- 8740964
TI  - Influence of zinc(II) binding on the structure of bovine alpha-lactalbumin.
AB  - The effect of Zn(II) binding on the structure of bovine alpha-lactalbumin (LA)
      was investigated. alpha-Lactalbumin, a regulatory subunit of lactose synthase,
      binds Ca(II) and Zn(II) at different sites in a mutually non-exclusive manner.
      The structures of the metal-depleted form of LA (apo-LA) and Ca(II)-bound LA
      (holo-LA) have been well characterized. Here, the effect of Zn(II) binding on the
      structure of holo-LA has been investigated by comparison with the structure of
      holo-LA and apo-LA using CD and NMR spectroscopy. The CD spectrum of Zn(II)-holo
      LA was similar to that of holo-LA, but the intensity of the negative peak in near
      UV region was decreased. Zn(II) binding to holo-LA produced only small changes in
      NMR chemical shifts, but the integral volumes of the cross-peaks of NOESY signals
      in cluster II, which is in the vicinity of Zn(II) binding site, were affected.
      Zn(II) binding induces a local structural change on the holo-LA, but it does not
      induce a large backbone conformational change.

PMID- 8740965
TI  - Synthesis, structure and stability of novel dimeric peptide-disulfides.
AB  - Oxidation of nonapeptide dithiol (2) with K3Fe(CN)6 leads to either monomeric
      disulfide (4) or antiparallel and parallel dimeric disulfides (3a and 3b)
      depending upon reaction conditions. When exposed to small amounts of thiols or
      cyanide in aqueous solution, these three species interconvert to an equilibrium
      mixture of 2:1:8 (3a:3b:4).

PMID- 8740966
TI  - Conformational comparison in the snake toxin family.
AB  - A theoretical method was applied to consensus sequences of several members of the
      snake toxin family as a further approach to examining their conformational
      homology. Some secondary-structure predictions as well as hydropathy profiles
      were also examined. A comparison of long neurotoxins themselves reveals a high
      homology degree. However, their C-terminal fragments show poor homology and the N
      terminal fragments appear as the region of maximum variability. Moreover, when
      the matrix includes the consensus sequence of the genus Laticauda (LNTX1),
      lacking the disulfide bridge 31-35, the method detects a lower conformational
      homology in a molecular region centered at position 31. Unlike long neurotoxins,
      the N-terminal segments of short neurotoxins show a high homology degree, but
      when comparing short with long neurotoxins, a poor correlation is found in this
      zone of the molecule. Cytotoxins studied exhibit an excellent conformational
      homology except when the consensus sequence of cytotoxin homologues CTXE is one
      of the proteins in the matrix. A comparison between cytotoxins and short
      neurotoxins reveals homology only in two segments belonging to a beta-sheet
      structure. A considerable degree of homology is found between the short
      neurotoxin group and calciseptin and fasciculin as well as between the long
      neurotoxin group and kappa-neurotoxins.

PMID- 8740967
TI  - Generation of soluble and active subtilisin and alpha-chymotrypsin in organic
      solvents via hydrophobic ion pairing.
AB  - With very low concentrations of anionic detergents, such as sodium dodecyl
      sulfate (SDS) and Aerosol OT (AOT), it is possible to solubilize proteases in
      organic solvents, while retaining enzymatic activity. For example, the SDS
      subtilisin BPN' complex catalyzes transesterification of Ac-Phe-OMe in ethanol
      with a kcat/Km of 36 M-1 s-1 for mutant M1 and 39 M-1 s-1 for the wild type. By
      comparison, M1 suspended in ethanol is approximately 1000-fold less active, with
      a kcat/Km of 0.03 M-1 s-1. Similarly, AOT complexes of alpha-chymotrypsin were
      found to be approximately 1000 times more active (kcat/Km = 100-350 M-1 s-1) than
      the suspended enzyme.

PMID- 8740968
TI  - Lability of N-alkylated peptides towards TFA cleavage.
AB  - Trifluoroacetic acid (TFA) is a common reagent in both solid-phase and solution
      peptide synthesis. It is used for the deprotection and/or cleavage of the
      synthesized peptide from the resin. The use of TFA under these standardized
      conditions is thought to be sufficiently mild, thereby preventing degradation of
      the desired product. However, peptides of the general structure R1-(N-alkyl X1)
      X2-R2 are hydrolyzed by standard TFA solid-phase peptide synthesis (SPPS)
      cleavage/deprotection conditions providing fragments R1-(N-alkyl X1)-OH and H-X2
      R2. The fragmentation is observed during a TFA cleavage both from the resin and
      in solution. The hydrolysis is proposed to proceed via an oxazolone-like
      intermediate in which equilibration of the chiral center of the N-alkylated
      residue occurs. This mechanism is supported by H/D exchange as observed MS and
      NMR in conjunction with HPLC.

PMID- 8740969
TI  - Amino monothio acids in solid-phase synthesis of peptide thioamides.
AB  - Peptides containing backbone thioamides (endothiopeptides) have been synthesized
      utilizing thioacylation under solid-phase conditions. The thioacylations were
      performed by activating N-protected amino monothio acids with the phosphorus
      containing coupling reagent 6-nitrobenzotriazol-l
      yloxytris(pyrrolidino)phosphoniu m hexafluorophosphate (PyNOP). This method
      avoids the use of P4S10-based O/S-exchange reagents, and it is thus amendable to
      amino acids with side-chain amides. Synthesis of endothio analogs of biologically
      active peptide such a pGlu-psi [CSNH]-His-Pro-NH2 (TRH) and Leu-Gln-psi [CSNH]
      Leu-Lys demonstrated this feature. Proton and carbon NMR spectra of the TRH
      analog verified the sequential position of its thioamide function. Compatibility
      of endothiopeptides with allylprotecting groups was studied, and 1,8
      diazabicyclo[5.4.0]undec-7-ene (DBU) was evaluated as a substitute for
      piperidine.

PMID- 8740970
TI  - Identification of the residues involved in homodimer formation of recombinant
      human erythropoietin.
AB  - Recombinant human erythropoietin (rHuEPO) is biologically functional when in a
      monomeric state; upon extensive heating, rHuEPO forms a dimer. The nature of this
      dimeric linkage was investigated after isolation of the dimer by gel filtration.
      The dimer fraction was subjected to tryptic digestion, and the peptides were
      separated by reversed-phase HPLC. SDS-PAGE, N-terminal sequencing, capillary
      electrophoresis and mass spectrometry (both liquid-chromatographic electrospray
      and matrix-assisted laser desorption ionization) were employed to compare the
      tryptic peptides from heat-treated rHuEPO and untreated rHuEPO. Results
      demonstrated that elevated heat broke the intramolecular disulfide bond between
      Cys-7 and Cys-161 and an intermolecular disulfide bond then formed from these
      residues, producing a covalently linked rHuEPO homodimer. Dimer formation was
      also mathematically modeled and shown to fit a simple equilibrium.

PMID- 8740971
TI  - Protection of asparagine and glutamine during N alpha-Bpoc-based solid-phase
      peptide synthesis.
AB  - In this paper we describe the synthesis and properties of Bpoc-Asn(Trt)-OH, Bpoc
      Asn(Trt)-OPfp, Bpoc-Gln(Trt)-OH and Bpoc-Gln(Trt)-OPfp. These derivatives are
      highly soluble in CH2Cl2 and can be coupled efficiently in solid-phase peptide
      synthesis. The peptides, acetyl-Ala-Phe-Asn(Trt)-Gly-Leu-Ala-O-Dbf-SH and Boc
      Cys(Acm)-Ala-Phe-Gln(Trt)-Gly-Leu-Ala-O-Dbf-SH (where O-Dbf-SH is the peptide
      ester of 4-mercapto-6-hydroxydibenzofuran) were synthesized by stepwise solid
      phase peptide synthesis using N alpha-Bpoc amino acids. We have observed that
      less than 0.1% of the trityl group is removed from the carboxamide of Gln and Asn
      during a standard 15 min N alpha-Bpoc deprotection in 0.5% TFA in CH2Cl2.

PMID- 8740972
TI  - Design and evaluation of small peptides mapping the exposed surface of IL-8.
AB  - In an effort to determine which regions of IL-8 are involved in interactions with
      its receptors, eight peptides were designed to correspond to distinct exposed
      regions of the IL-8 monomer, using the proton NMR-derived structure of the dimer
      as a basis. The peptides were evaluated singularly, and as equimolar mixtures of
      two to six peptides, in an IL-8 receptor binding assay and found to have no
      binding interaction with either alpha or beta IL-8 receptor as single peptides or
      mixtures of two peptides. In contrast, one of these peptides having the sequence
      AVLPRSAKEL, which corresponds to the N-terminal 10 amino acid residues of the 77
      amino acid form of IL-8, exhibited potent chemotactic activity in human
      neutrophils. These results indicate that there is no contiguous ligand that can
      be designed based on the NMR and X-ray determined structure of IL-8 and that
      there may be multiple receptors responsible for neutrophil activation and
      chemotaxis.

PMID- 8740973
TI  - Steric constraints in the recognition of peptide substrates for the epidermal
      growth factor receptor kinase.
AB  - Epidermal growth factor (EGF) stimulates cellular mitogenesis by binding to and
      activating its membrane-associated receptor. An important component of signal
      transduction by the activated receptor is the stimulation of an intrinsic tyrosyl
      residue-specific protein kinase, which selectively phosphorylates tyrosyl
      residues in the cytoplasmic tail of the receptor and in other cytoplasmic
      substrates. A recent study utilizing tyrsub, a new high affinity synthetic
      peptide substrate for the EGF receptor kinase, provided evidence that in peptide
      substrate binding, the tyrosyl residue plays the central role in recognition,
      with residues surrounding the tyrosyl residue contributing to stabilization of
      docking [Guyer et al. (1994) Arch. Biochem. Biophys. 312, 573-578]. A large body
      of previous work had identified acidic residues near the site of phosphorylation
      as most important for binding; therefore, other residues in tyrsub appeared to be
      promising sites for locating spectroscopic reporter groups. Since tyrsub has
      neutral residues -4 and +4 residues from the site of phosphorylation, we prepared
      two analogs of tyrsub, in each of which one of those residues was substituted
      with Cys. These cystyrsubs were found to be effectively phosphorylated by EGF
      receptor prepared from A431 cells, on stimulation with EGF, with high affinities
      [Km(app) = 40-50 microM.] Modification of the cystyrsubs with iodoacetamide had
      no deleterious effect on the ability of the peptide to be phosphorylated by the
      EGF receptor kinase, while the labeling by 5-iodoacetimidofluorescein completely
      abolished the productive interaction between the peptide and the EGF receptor.
      This unexpected failure of the fluorescently labeled peptides to be
      phosphorylated does, however, provide information on steric limitations to
      recognition of substrates by the EGF receptor kinase.

PMID- 8740974
TI  - Is citrate an inhibitor of calcium oxalate crystal growth in high concentrations
      of urine?
AB  - The effect of citrate on calcium oxalate (CaOx) crystal growth was studied in a
      system in which series of samples containing [45Ca]calcium chloride were brought
      to different levels of supersaturation with various concentrations of oxalate.
      The crystallization was assessed by measuring the amount of isotope remaining in
      solution 30 min after the addition of CaOx seed crystals to samples containing
      citrate in concentrations corresponding to those in final urine. The experiments
      were carried out both in pure salt solutions and in solutions with dialysed
      urine. Increased concentrations of citrate resulted in a reduced crystallization
      of CaOx in both the presence and absence of dialysed urine, but with the lowest
      rate of crystallization in the samples containing urine. The increased
      concentration of 45Ca remaining in solution reflected a reduced crystallization,
      which could possibly be explained both by a reduced supersaturation and by an
      increased inhibition of CaOx crystal growth. The direct effects of citrate on
      CaOx crystal growth were assessed by calculating the ion-activity product of CaOx
      (APCaOx) at corresponding degrees of crystallization. The APCaOx recorded at a
      30% reduction of the amount of isotope in solution increased with increasing
      concentrations of citrate between 1.0 and 1.5 mmol/l samples both with and
      without dialysed urine. These findings indicate that citrate has a weak direct
      inhibitory effect on CaOx crystal growth, which adds to the reduced growth rate
      brought about by urinary macromolecules and a decreased supersaturation.

PMID- 8740975
TI  - Potential contribution of optional urease-positive bacteria to idiopathic urinary
      calcium stone formation. II. Microlith formation kinetics in a fermenter model of
      the urinary tract infected by optional urease-positive microorganisms.
AB  - We investigated the effects of weak to moderate urease hydrolysis by optional
      urease-positive microorganisms in an artificial urine model enriched with calcium
      phosphate and calcium oxalate in respect of calcium stone formation. The
      incubation experiments were performed using a discontinuously running fermenter
      device to simulate the urinary system. The kinetics of cell division rates, pH
      and ammonium ion production were measured and correlated to crystallite
      appearance in the incubation medium. Qualitative analyses of the sediments
      revealed apatite. Investigations using light microscopy and scanning electron
      microscopy (SEM) confirmed the matrix effect of bacterial glycoproteins. It was
      shown that initiation of calcium oxalate stone formation is in all probability
      equally determined by matrix effects and by heteronuclear crystallization if the
      urinary tract is infected by optional urease-positive bacteria. When urinary
      inorganic phosphate is present, calcium phosphate nidi are always initially
      formed, and may subsequently be coated by calcium oxalate.

PMID- 8740976
TI  - Isoelectric focusing of Tamm-Horsfall glycoproteins: a simple tool for
      recognizing recurrent calcium oxalate renal stone formers.
AB  - Tamm-Horsfall glycoproteins (THPs) from healthy probands and a majority of
      recurrent calcium oxalate renal stone formers reveal different physicochemical
      properties when analyzed using isoelectric focusing (IEF). The pI values of THPs
      from healthy probands are approximately 3.5 while THPs from recurrent renal stone
      formers have pI values of between 4.5 and 6. The two groups of THPs exhibit
      completely different protein patterns. The differences in IEF analysis allow
      differentiation between THPs from healthy probands and recurrent calcium oxalate
      stone formers and may possibly be used as a simple diagnostic method for the
      recognition of recurrent calcium oxalate renal stone formers.

PMID- 8740977
TI  - Microcalorimetric measurements carried out on isolated tumorous and nontumorous
      tissue samples from organs in the urogenital tract in comparison to histological
      and impulse-cytophotometric investigations.
AB  - In this comparative study, microcalorimetric measurements were carried out on a
      total of 96 tumorous and nontumorous tissue samples taken from organs of the
      urogenital tract using a thermal activity monitor (TAM). Changes in the heat
      emission of the tissue samples were measured at 1-min intervals and graphically
      displayed as a function of time. The aim of the study was to compare the
      microcalorimetric results with impulse-cytophotometric and histological findings
      and provide evidence for the metabolic activity of tumorous and nontumorous
      tissue. In order to obtain the variation in metabolic activity, the maxima (Pmax)
      of the curves were determined as a value of the maximum thermal power of a tissue
      sample, the mean values (P) were determined by the mean thermal power and the
      contour integrals (W) were defined by the behavior of the energy reserves and
      their mobilization. The first part of the study was carried out to investigate
      whether tumorous and nontumorous tissue samples differ in general according to
      their metabolic activity. We discovered, using the parameters described above,
      that in general tumorous tissue exhibited a higher metabolic activity than
      nontumorous tissue samples. For example, both W and P in tumorous prostate tissue
      samples were eightfold higher and the (Pmax) value was 8.4-fold higher than in
      normal tissue. Additional investigations on testicle and kidney tissues were
      performed to find a possible correlation between microcalorimetric results and
      histological grading. We found that an increasing malignancy correlated with a
      higher metabolic activity of the tissue. Based upon these results we were able to
      differentiate the various histological gradings of these tumorous tissues by
      microcalorimetric measurements. The results show it is possible to differentiate
      between normal and tumorous tissue samples by microcalorimetric measurement based
      on the distinctly higher metabolic activity of malignant tissue. Furthermore,
      microcalorimetry allows a differentiation and classification of tissue samples
      into their histological grading. With the help of microcalorimetry, it might be
      possible in future to detect and record the metabolic processes of isolated
      tissue structures and changes in these activities as a result of medical
      intervention such as cytostatic treatment.

PMID- 8740978
TI  - In vivo, synergestic inhibition of MAT-LyLu rat prostatic adenocarcinoma growth
      by polyamine deprivation and low-dose cyclophosphamide.
AB  - Polyamine deprivation in vivo produces significant tumor growth inhibition of the
      hormone-resistant, metastatic Dunning Mat-LyLu murine prostatic carcinoma. In
      order to produce a cytotoxic effect in addition to the cytostatic effect of
      polyamine deprivation, various chemotherapy regimens, combined with drug
      containing polyamine-deficient chow (DC-PDC), were assessed. Triple chemotherapy
      combining methotrexate, cyclophosphamide and vindesine; and monochemotherapy with
      high-dose cyclophosphamide (90 mg. kg-1) and low-dose cyclophosphamide (20 mg.kg
      1) were studied alone and in combination with DC-PDC. A variant of DC-PDC
      excluding the polyamine oxidase inhibitor MDL 72527 was also studied in
      combination with low-dose cyclophosphamide. The triple-chemotherapy regimen alone
      or in combination with polyamine deprivation was effective on tumor growth
      inhibition but was also toxic. High-dose cyclophosphamide alone produced
      significant tumor growth inhibition and an increase in life span. High-dose
      cyclophosphamide in combination with DC-PDC was also effective on tumor growth
      but was also toxic. Low-dose cyclophosphamide alone was moderately effective on
      tumor growth inhibition with a marginal increase in life span. When combined with
      polyamine deprivation, results with low-dose cyclophosphamide compared favourably
      with those of high-dose cyclophosphamide alone and prevented the formation of
      lung metastases. The polyamine oxidase inhibitor does not appear to be mandatory
      to achieve this effect if DC-PDC is combined with low-dose cyclophosphamide.
      Polyamine deprivation appears to be an important tool in anticancer therapy,
      allowing the use of reduced doses of cytotoxic agents with the same antitumoral
      efficacy.

PMID- 8740979
TI  - Circulating immune markers in advanced renal cell carcinoma during immunotherapy
      with interferon gamma.
AB  - Circulating immune markers sICAM-1, sELAM-1, sMHC-I, beta 2-MG, sCD4 and sCD8
      were evaluated prior to and during immunotherapy with biologically active doses
      of interferon gamma (IFN-gamma) in 16 patients with advanced renal cell carcinoma
      (RCC) over a period of 12 months. Compared to 20 healthy controls, significantly
      (P < 0.01) elevated baseline levels of circulating adhesion molecules sICAM-1
      (mean 1166 vs 230 ng/ml) and sELAM-1 (70 vs 17 ng/ml) were found in all patients.
      Compared to responders (n = 2) or patients with stable disease (n = 2),
      progressive disease during therapy (n = 12) was associated with significantly (P
      < 0.05) higher mean concentrations of sICAM-1 (1574 vs 962 ng/ml) and sELAM-1 (86
      vs 46 ng/ml). Pretherapeutic and intratherapeutic levels of sMHC-I among the RCC
      patients were significantly (P < 0.05) lower than among the controls (0.41 vs 0.8
      ng/ml). sCD4 levels clearly showed the same tendency (24 vs 33 U/l). sCD8
      baseline levels, by contrast, were significantly (P < 0.05) elevated (564 vs 336
      U/l), reflecting either activation of the NK-cell subset or increased synthesis
      of CD8+ T-suppressor cells. Again, significantly (P < 0.05) higher
      intratherapeutic sCD8 concentrations were observable with progressive disease
      than with response to therapy or stable disease (721 vs 355 U/l). Interestingly,
      although the biologically active dose of IFN-gamma was defined by an increase in
      beta 2-MG release of at least 30% within 48 h after injection, none of the other
      markers showed any significant alteration following IFN-gamma administration,
      suggesting that IFN-gamma in vivo does not produce changes in circulating markers
      of activation that might be expected on the basis of its effects in vitro. The
      finding of significantly elevated concentrations of sICAM-1, sELAM-1 and sCD8 in
      the presence of low sCD4 and sMHC-I levels might be of clinical significance for
      indicating ongoing tumor progression.

PMID- 8740980
TI  - Polymerase chain reaction in the diagnosis of urinary tract tuberculosis.
AB  - The polymerase chain reaction (PCR) is a technique that can be used to amplify a
      specific DNA genomic sequence, whereby the presence of an extremely small number
      of bacteria can be detected. The high sensitivity of PCR is particularly useful
      in paucibacillary situations such as non-pulmonary tuberculosis (TB). The aims of
      the present study were to establish a PCR assay for the rapid detection of
      Mycobacterium tuberculosis (MTb) in urine, to compare the sensitivity of PCR with
      routine culture technique (Bactec) and to determine the optimal type of urine
      specimen for PCR detection of MTb. In the first phase of the study, a total of 92
      urine specimens were collected from 83 patients with suspected urinary tract TB.
      Two urine specimens in 2 patients were positive for TB by both PCR and Bactec,
      while 90 specimens from 81 patients were negative by both methods. Inhibition of
      PCR was present in nine urine specimens (10%). In the second phase of the study,
      a further seven patients were selected for intensive investigation to determine
      the optimal urine sampling for PCR detection of MTb. The conclusions of the study
      are that PCR can provide much faster confirmation of urinary TB (within 24-48 h)
      than Bactec urine culture (which may take several weeks). About 10% of urine
      specimens could not be evaluated by PCR due to the presence of inhibitory
      substances of unknown nature. MTb organisms were found to be excreted
      intermittently in the urine of infected patients, and single specimens were more
      likely to be false negative than a 24-h sample. The best method appeared to be
      the concentration of a large volume of urine, for instance 11 concentrated to 2
      ml.

PMID- 8740981
TI  - The ileopsoas tunnel, a new antireflux technique for ureteroileal reimplantation:
      an experimental study in dogs.
AB  - A new antirefluxing ureteroileal anastomosis is described in which the implanted
      ureter is placed between the ileal segment and psoas muscle. The procedure was
      studied in eight experimental dogs, which were observed for 20 weeks. Radiologic
      and bacteriologic examinations, necropsy assessment and histopathologic results
      provided evidence that this ileo-psoas tunnel technique allows a unidirectional,
      non-obstructed flow of urine. The technique could be applied when ileal
      replacement of the ureter is necessary or in association with continent bladder
      replacement.

PMID- 8740982
TI  - A retrospective quality analysis of 102 randomized trials in four leading
      urological journals from 1984-1989.
AB  - The objective of the present study was to analyse critically the quality of the
      reporting in 102 randomized trials from four leading urological journals from
      1984 to 1989 on the basis of an evaluation system we have developed. This
      comprises 21 principal parameters selected in terms of their significance for the
      validity of the studies. These parameters were evaluated by two readers
      independently of each other as to whether they were specified, not specified,
      could not be evaluated or were not applicable. The study score of each paper
      resulted from the sum of all specified criteria. In the 102 studies, out of 21
      criteria 69.1% and 69.8% (investigators A and B, respectively) were reported;
      29.8% and 29.4%, respectively were not reported, 0.4% and 0.1%, respectively,
      could not be evaluated and 0.7% did not apply. Such important principal
      parameters as the sample size (6.9% and 7.8%, respectively), statistical power
      (11.8%), method of randomization (22.5% and 23.5%, respectively), patient
      blinding (30.4%), investigator blinding (33.3%), loss to follow-up (34.8% and
      35.3%, respectively) and rate of discontinuation (36.0% and 37.7%, respectively)
      were mentioned least often. The study score of all investigations ranged from
      20.5 (97.6%) to 9.0 (42.9%) points. Most (60/59% and 62/61%, respectively)
      attained values between 16 (76.2%) and 13 (61.9%). Accordingly, randomized trials
      in urological journals show similar deficits to those in internal medicine,
      surgery and intensive care medicine. A particular problem is that they concern
      the most important techniques for systematic reduction of inadvertent errors
      (bias), and thus doubt is cast upon the hardcore of controlled studies. If it is
      possible for many authors to mention individual criteria completely, this should
      also apply (and in particular) to the most critical parameters. In our opinion,
      the 21 criteria selected for an evaluation system constitute a practical
      compromise between the 3 and 38 criteria alternatively suggested by other
      authors. Moreover, use of a comprehensive check list should be the precondition
      for acceptance of papers for publication.

PMID- 8740983
TI  - Evolution of the neuropathology of Alzheimer's disease.
AB  - Our knowledge of the etiology and pathogenesis of Alzheimer's disease is limited.
      The most conspicuous changes seen in the brain are deposits of insoluble proteins
      in both extracellular and intraneuronal locations. The extracellular deposits
      consist primarily of a specific A4 amyloid protein. The significance of these
      deposits remains to be determined, as they are often found in the cerebral cortex
      of non-demented elderly persons. More telling is the gradual accumulation of
      insoluble fibrous material within some neurons that consists mainly of abnormally
      phosphorylated tau protein. Six stages of increasingly severe cortical
      destruction can be distinguished. Stages I and II are characterized by
      neurofibrillary changes that are largely confined to the transentorhinal region,
      whereas stages III and IV are marked by severe involvement of both the entorhinal
      and transentorhinal regions. Isocortical destruction occurs during stages V and
      VI. This progression in cortical pathology correlates with the gradual worsening
      of clinical symptoms.

PMID- 8740984
TI  - Molecular genetics of Alzheimer's disease.
AB  - Four genes have thus far been implicated in the etiology of Alzheimer's disease
      (AD). A series of mutations in the amyloid precursor protein (APP) gene on
      chromosome 21, which cause disease with a typical onset of 55 years of age, have
      been described. These include mutations at APP670/671, APP692, and APP717. The
      epsilon 4 allele of the apolipoprotein E (ApoE) gene on chromosome 19 is
      positively associated with disease, whereas the epsilon 2 allele is usually
      negatively associated with disease. Mutations in the S182 gene on chromosome 14
      seem to cause disease with an onset age of < 50 years and mutations in a gene on
      chromosome 1 (S182 Like Protein: S182LP) cause disease with variable onset. These
      genetic findings are reviewed within the framework of the amyloid cascade
      hypothesis of AD etiology and pathogenesis. The occurrence and effects of the
      mutations in APP and the fact that the epsilon 4 allele of ApoE are genetic risk
      factors point to the hypothesis that the extracellular deposition of beta-amyloid
      is the key initiating event in the pathogenesis of AD.

PMID- 8740985
TI  - Oxidative metabolism deficiencies in brains of patients with Alzheimer's disease.
AB  - Glucose metabolism in the brain has an important influence on many normal
      cellular processes. It contributes to the synthesis of acetylcholine, glutamate,
      aspartate, gamma-aminobutyric acid, glycine, and ATP production (the driving
      force behind almost all cellular and molecular activity). Neuronal glucose
      metabolism is controlled antagonistically by insulin and cortisol.
      Desensitization of the neuronal insulin receptor causes abnormalities in
      oxidative energy metabolism. During normal aging, the cerebral energy pool is
      slightly diminished, but its level increases after stressful events. In age
      related sporadic late-onset dementia of the Alzheimer type (SDAT), glucose
      metabolism and formation of cellular energy are severely reduced. Desensitization
      of the neuronal insulin receptor seems to be an early event in the pathogenesis
      or even etiology of SDAT causing disturbances in oxidative glucose metabolism and
      energy failure in insulin-sensitive brain structures. These abnormalities appear
      to induce a cascade of disturbances that leads to abnormal APP processing and
      amyloid formation, membrane damage, and neuronal death.

PMID- 8740986
TI  - Neurotransmitters, signal transduction and second-messengers in Alzheimer's
      disease.
AB  - It has long been assumed that widespread changes in postsynaptic neurotransmitter
      receptor function are not a feature of the disrupted neurotransmission seen in
      the brains with Alzheimer's disease (AD). However, recent evidence from
      postmortem brain and fibroblast studies suggests that both the neurotransmitter
      receptor/G-protein-modulated adenylyl cyclase and the phosphatidylinositol
      hydrolysis signal transduction cascades are disrupted in AD. Such disruptions may
      severely limit the functional integrity of key receptor types and undermine
      pharmacological attempts to ameliorate disease symptomatology through
      neurotransmitter replacement strategies. The involvement of some signalling
      mechanisms in the regulation of beta-amyloid precursor protein metabolism
      suggests also that disrupted signal transduction may exacerbate AD pathology.

PMID- 8740987
TI  - Epidemiology of Alzheimer's disease and current possibilities for prevention.
AB  - Many epidemiological studies of Alzheimer's disease (AD) have been conducted.
      This review discusses the most recent findings in relation to the possibilities
      of prevention of this disease. Data on the diagnostic validity are also reported.
      The primary prevention of AD is hampered by limitations in the knowledge and
      understanding about its risk factors. Among the factors that have been
      investigated, only age, familial aggregation, and apolipoprotein E gene-e4 allele
      are definite risk factors both for early- and late-onset AD. However, many of the
      possible and putative risk factors, if definitely confirmed, can be prevented or
      controlled. Secondary prevention is not currently practicable as valid predictive
      tests and efficacious treatment are lacking. In contrast, much data is available
      to support tertiary prevention interventions, such as better planned patient
      care.

PMID- 8740988
TI  - Classification of dementia and Alzheimer's disease.
AB  - Classification of dementia involves the recognition of its presence, followed by
      the differential diagnosis of its cause. Informant-based methods for dementia
      detection can be highly sensitive, even when cognitive impairment is mild.
      Alzheimer's disease (AD) is by far the leading cause of dementia; standardized
      clinical criteria result in high diagnostic accuracy rates. Classification of
      other dementing disorders is less satisfactory, particularly because there is
      frequent clinical and pathological overlap with AD. After AD, the most common
      causes of dementia are vascular dementia and dementia in persons with Parkinson's
      disease. Less common dementias include progressive supranuclear palsy,
      Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, and inherited
      metabolic disorders, most of which are extremely rare. Identifying the cause of
      dementia is important because some forms can be treated with currently available
      therapies. In instances involving genetically transmitted disease, genetic
      testing and counseling of family members may be advisable.

PMID- 8740989
TI  - Clinical subgroups of the Alzheimer syndrome.
AB  - During the last decade, senile dementia and the presenile disease that was named
      after Alois Alzheimer have been considered a single entity called Alzheimer's
      disease (AD). This same decade has witnessed the development of many diagnostic
      tools, such as CT, MRI, and SPECT imaging, that have made possible the systematic
      analysis of symptoms of brain disorders. With the aid of these sophisticated
      techniques, it is possible to divide the disorder into clinically relevant
      subgroups, one of which corresponds to the disease first described by Alzheimer.
      The disease exists in sporadic and familial forms, and in subgroups of these two
      basic types. Because the heterogeneity of AD is incontestable, it is time to
      reconsider the current use of the term "Alzheimer's disease." Because it labels
      different subgroups whose characteristics are often markedly different, the term
      "Alzheimer syndrome" appears to be more appropriate.

PMID- 8740990
TI  - Diagnosis of dementia at the primary care level.
AB  - In Sweden, as in many other industrial countries, the majority of patients with
      symptoms of dementia are initially evaluated by a general practitioner (GP), and
      many do not receive a follow-up assessment by a specialist. Accordingly, GPs play
      a vital role in identifying patients with possible dementia and undertaking
      additional diagnostic procedures. Currently, however, the ability of most GPs to
      perform assessments for dementia is limited. It is important that tests to
      confirm the presence of dementia be performed uniformly, irrespective of the
      specialty of the examining physician. Once a diagnosis of dementia has been
      established and appropriate living arrangements for the patient have been made,
      the GP should continue to monitor the patient's health status. In Sweden,
      "dementia teams" of health care professionals have been successful in providing a
      consistently high level of care to patients with dementia, reducing the incidence
      of hospitalization for acute illness.

PMID- 8740991
TI  - Neuropsychological features of early Alzheimer's disease: preclinical and
      clinical stages.
AB  - In the preclinical stage of Alzheimer's disease (AD), studies of asymptomatic
      mutation carriers have identified impairments in episodic memory. Other cognitive
      functions show no or slight impairment suggesting that preclinical AD is a
      unifunctional cognitive syndrome; the brain is affected selectively and
      predominantly in the medial temporal structures. In the early clinical stage,
      deficits occur in episodic memory, verbal abilities, visuospatial functions,
      attention, and executive functions. AD becomes a multifunctional cognitive
      syndrome and the brain's association cortices are affected. Nevertheless, sensory
      motor performance and procedural memory seem to be intact and only slight
      impairment may be seen in primary memory. In advanced AD, cognitive dysfunction
      including deficits is global in primary memory, although sensory-motor
      performance may be well preserved. The brain's association cortices are severely
      affected. The sequence of cognitive decline; from unifunctional to global
      deficits, conforms to the three-stage development of neurofibrillary tangles
      described by Braak and Braak.

PMID- 8740992
TI  - Diagnosis of Alzheimer's disease: defining genetic profiles (genotype vs
      phenotype).
AB  - The early identification of Alzheimer's disease (AD) requires a multifactorial
      diagnostic approach. Components of a comprehensive assessment include a clinical
      examination, neuropsychological and psychometric evaluations, biochemical tests,
      cardiovascular and radiological examinations, neuroimaging, brain bioelectrical
      activity mapping, an evaluation of brain hemodynamics, and assessment of
      biological markers. Genetic testing should be incorporated into the diagnostic
      protocol only for research purposes and risk evaluation. The genetic
      characterization of familial AD genotypes (FAD-21, FAD-14, FAD-1, FAD-19, APP
      21m) can help define the phenotypic profiles of AD clinical subtypes. The
      correlation of genotypic and phenotypic profiles might have a predictive value in
      terms of AD diagnosis and therapeutic responses to particular drugs. However,
      available genetic markers (APP-21m, APO-E) are not yet conclusive for diagnostic
      purposes. In contrast, AD-related Apo-E genotypes appear to correlate with
      defined AD phenotypes. The presence of an Apo-E4 allele seems to represent an
      important risk factor for dementia.

PMID- 8740993
TI  - Biological markers and diagnostic investigations in Alzheimer's disease.
AB  - The diagnosis of Alzheimer's disease (AD) is based on numerous clinical,
      neuroradiological, neurophysiological, and neuropsychological evaluations, but a
      definitive diagnosis can only be established at autopsy or by brain biopsy.
      Because the need for a simple and accurate diagnostic marker is increasing as new
      drug treatments emerge, intensive research to identify diagnostic markers is now
      in progress. Computer tomography and magnetic resonance imaging are being used to
      compare linear and volumetric measurements of brains for patients with AD and
      normal controls. Functional imaging techniques, such as single photon emission
      computer tomography and positron emission tomography, are being used to identify
      possible disease-related changes in regional blood flow, glucose metabolism, and
      receptor activities. Elevated tau-protein concentrations or reduced levels of
      beta-amyloid precursor protein in the cerebrospinal fluid; mutations on
      chromosomes 14, 19, and 21; the presence of the Apo-epsilon-4 allele; and
      impaired odor identification are also being evaluated as possible markers.

PMID- 8740994
TI  - The differential diagnosis of dementia.
AB  - Dementia is misdiagnosed in up to 15% of cases referred for further assessment.
      Real or apparent cognitive impairment is usually a prominent clinical feature of
      the most common differential diagnoses, including normal aging, depression,
      nonaffective psychoses, delirium, and amnestic syndromes. To date, no practical
      biological marker exists to aid in diagnosing dementia. However, other conditions
      that are frequently amenable to treatment can usually be differentiated from
      dementia following detailed clinical assessment and the use of appropriate
      diagnostic criteria. Some considerations that aid in distinguishing dementia from
      other conditions include: rates of onset and progression; duration of symptoms;
      fluctuations in the intensity and pattern of symptoms; the pattern and extent of
      cognitive impairment and its effect on activities of daily living; alterations in
      the level of consciousness; the presence of affective and psychotic symptoms;
      past medical, family, and psychiatric history, including information about
      current medications, substance abuse, and premorbid personality.

PMID- 8740995
TI  - Pharmacologic treatment of noncognitive symptoms of dementia.
AB  - Cognitive deterioration in dementia includes many changes besides memory
      disturbances, including agitation, delusions, hallucinations, anxiety,
      irritability, and aggressiveness. Antipsychotic drugs are often used to control
      behavioral symptoms, but their benefits are limited. Depression, which is common
      in dementia, is often associated with anxiety. Selective serotonin reuptake
      inhibitors (SSRIs) improve mood and reduce anxiety while causing few side
      effects; they are also useful in managing irritability. Thus, the SSRIs should be
      considered the agents of choice for treating noncognitive symptoms associated
      with dementia. Neuroleptics should be used exclusively in patients with severe
      behavioral or psychotic symptoms, and only those agents without anticholinergic
      effects should be administered. Neuroleptics can be coadministered with SSRIs in
      patients who are extremely aggressive. Anxiolytics may also be effective for
      shortterm use. Future studies of drugs to treat the noncognitive symptoms of
      dementia should be placebo controlled and should evaluate the effects of those
      drugs on cognitive function.

PMID- 8740996
TI  - Caring for demented patients.
AB  - According to E.H. Erikson, the developmental task of old age consists of looking
      back and remembering one's life, accepting and taking responsibility for the
      past, imagining the future, and living toward death. Dealing with this final life
      crisis and achieving wholeness and meaning is a difficult task for the healthy
      person, and it is vastly more difficult for the elderly person with dementia.
      Those who care for elderly patients with dementia must remember for them, see
      their future as they would have seen it, and know and respect their philosophy of
      life. They must also know how to communicate with their patients in order to
      reach them, a task that is often arduous and frustrating. The patient's
      experience of wholeness and meaning must be promoted during all caregiving
      activities. Caregivers must be encouraged to experience their patients as unique
      and valuable persons.

PMID- 8740997
TI  - Utilizing compensatory task conditions for episodic memory in Alzheimer's
      disease.
AB  - Numerous recent studies have addressed the question of whether memory can be
      improved in patients with Alzheimer's disease (AD). Evidence from both
      experimental studies and intervention work suggests that AD exerts a substantial
      effect not only on memory functioning in general, but also influences the
      potential for memory improvement. Contrary to previous claims, however, several
      recent studies indicate that AD patients can utilize cognitive support to improve
      memory under certain conditions. To achieve performance gains from experimental
      manipulations or intervention procedures in AD, it appears that cognitive support
      must be provided at the time of both information acquisition and subsequent
      information retrieval. In addition, there is evidence that cognitive intervention
      in AD stands a greater chance of succeeding when the training is based on
      functions that are relatively well preserved as opposed to functions that are
      severely impaired.

PMID- 8740998
TI  - Evaluation of tacrine hydrochloride (Cognex) in two parallel-group studies.
AB  - The efficacy of tacrine hydrochloride (Cognex) for the treatment of Alzheimer's
      disease (AD) has been confirmed in two randomized, double-blind, placebo
      controlled, parallel-group studies. More than 1100 patients with mild to
      moderate, probable AD were randomized to receive placebo or tacrine for 12 or 30
      weeks. Outcome measures included objective assessments of cognitive function,
      qualitative assessments of treatment response from the caregiver and clinician
      perspective, and assessments of activities of daily living. Statistically
      significant treatment effects favoring tacrine were demonstrated in each domain.
      These results suggest several considerations for clinicians. Because response to
      treatment is dose related, patients should be titrated to their maximum tolerated
      dose. Response may be subtle and may range from improvement to stabilization or
      slowed decline. A minimum treatment period of 6 months is recommended to evaluate
      a response and treatment should be continued depending on patient tolerability.

PMID- 8740999
TI  - Use of tacrine hydrochloride (Cognex) in private practice.
AB  - Before administering tacrine hydrochloride (Cognex), an examination is conducted
      that includes a medical history, neurological examination, laboratory studies,
      EEG, CT or MRI, and sometimes lumbar puncture. Much consideration by physicians
      patients, and caregivers goes into the decision to prescribe Cognex. Aside from a
      diagnosis of mild to moderate Alzheimer's disease, the patient must be in good
      health. Patient and caregivers must accept the need for weekly ALT measurements
      for at least the first 18 weeks of treatment, and for periodic office
      evaluations. Many of our patients who have received Cognex show considerable
      improvement in overall sense of well-being, affect, and the abilities to converse
      and participate in daily activities. The most common adverse effects in our
      patients are nausea, vomiting, and gastrointestinal upset. In our experience,
      administration of Cognex extends the time that patients with AD can function in a
      home environment. This approach often represents a cost savings to the patient's
      family.

PMID- 8741000
TI  - Treatment of Alzheimer's disease: future directions.
AB  - Following the introduction of tacrine hydrochloride (Cognex) in the United States
      and several other countries, researchers are pursuing two broad therapeutic
      strategies for Alzheimer's disease (AD). The first involves identifying agents or
      combinations of agents whose actions can compensate for the considerable cerebral
      damage that has typically occurred by the time the diagnosis of AD is made. Such
      therapeutic approaches include the development of additional cholinesterase
      inhibitors, agents that work on the receptors of other systems damaged by the
      disease process, and anti-inflammatory and immunomodulatory agents. The second
      and ultimately more promising strategy involves the development of approaches to
      retard, halt, or even prevent disease progression. Such protective approaches,
      which depend on the development of more effective methods for predicting and
      diagnosing AD, include the administration of nerve growth factor and other
      neurotrophins and the use of pharmacologic or genetic interventions to limit
      amyloid deposition and the formation of neurofibrillary tangles.

PMID- 8741001
TI  - Functional studies of new drugs for the treatment of Alzheimer's disease.
AB  - Few treatments for Alzheimer's disease (AD) have been evaluated to date by
      studying their effects on functional brain activity. Neuroimaging techniques such
      as positron emission tomography (PET) and single photon emission computed
      tomography (SPECT) are important tools that can provide an increased
      understanding of functional correlates to biological and structural changes in
      brains of patients with AD. These techniques provide valuable information about
      effects of drug treatments on functional parameters including blood flow, glucose
      metabolism, and neurotransmitter activity. Functional study outcomes are
      especially valuable when they are combined with studies of the effect of
      treatment on EEG and cognitive tests. This paper discusses functional changes
      observed in the brains of patients with AD following treatment with tacrine or
      nerve growth factor. Although these agents represent different approaches to
      cognitive drug treatment for AD, functional study outcomes indicate that both
      drugs improve cholinergic activity in the brain during long-term treatment.

PMID- 8741002
TI  - Future prospects for Alzheimer's disease therapy: ethical and policy issues for
      the international community.
AB  - In addition to being driven by basic scientific research and the preclinical and
      clinical evaluation of promising new compounds, the development of drugs for
      patients with Alzheimer's disease (AD) must also be guided by public policy and
      ethical considerations. More carefully coordinated efforts should be devoted to
      reducing caregiver burden and providing community-based health care services for
      patients with chronic as opposed to acute diseases. Important ethical issues
      include the appropriate duration of double-blind, placebo-controlled clinical
      trials, the determination of the meaning of "informed consent" when dealing with
      patients with dementia, the establishment of outcome goals for various stages of
      the disease process, and the provision of appropriate hospice-type care. The
      establishment of the International Working Group on Harmonization of Dementia
      Drug Guidelines is an important step in the process of achieving an international
      approach toward the development and evaluation of drugs for patients with AD.

PMID- 8741003
TI  - Molecular chaperones and disease.
AB  - Molecular chaperones are intracellular protein-folding proteins which form part
      of an ancient cellular response to stress called the heat shock response. They
      have been the focus for attention during the last decade because of the discovery
      of their vital role in cell functioning. In very recent years additional roles
      for these 'topologically-active' proteins in the process of tissue pathology and
      its treatment have been indicated and are reviewed.

PMID- 8741004
TI  - Complete prevention of the clinical expression of adjuvant-induced arthritis in
      rats by cyclosporin-A and lobenzarit: the regulation of lymph node cell
      populations and cytokine production.
AB  - A single dose of either cyclosporin-A (CsA) or lobenzarit (CCA) given with an
      arthrogenic adjuvant completely prevented expression of experimental adjuvant
      arthritis in rats. The aim of this study was to understand how these drugs
      prevented the arthritis expression by studying the popliteal lymph nodes draining
      the arthritic joints at various times after adjuvant injection. Neither drug
      affected the proliferation in popliteal lymph nodes at the time arthritis was
      normally expressed, however, there was a marked change in the types of cells
      present. Immunofluorescence assays showed a reduction in the proportion of CD4+
      cells, while the proportion of B-lymphocytes was almost doubled. This coincided
      with a marked elevation in the ability of these cells to produce interleukin (IL)
      6. At the same time production of other cytokines (IL-2, tumour necrosis factor
      (TNF) and interferon (IFN)-gamma) was not greatly affected. However, one day
      after adjuvant injection IL-2 and IFN-gamma production was reduced. In vitro
      experiments showed that IL-6 production by lymphoid cells was relatively
      unaffected by CsA and CCA but IL-2, TNF and IFN-gamma were suppressed by CsA. The
      results indicate that CsA and CCA may modify the response to the arthritic
      adjuvant by specifically inhibiting IL-2, TNF and IFN-gamma production at the
      time of adjuvant injection. The lack of inhibition of IL-6 by these drugs reveals
      it may not play a key role in the initiation of this model of chronic
      inflammation.

PMID- 8741005
TI  - Inhibition of PAF-, LPS-, and cytokine-induced granulocyte accumulation in guinea
      pig lung by dexamethasone: evidence that inhibition of IL-5 release is
      responsible for the selective inhibition of eosinophilia by glucocorticoids in
      guinea-pigs.
AB  - The potency of dexamethasone has been determined as an inhibitor of
      intratracheally administered platelet activating factor- (PAF), or interleukin
      (IL)-5-induced eosinophilia, and of lipopolysaccharide-(LPS), tumour necrosis
      factor alpha-(TNF alpha) or cytokine-induced neutrophil chemoattractant- (CINC)
      induced neutrophilia in guinea-pig lungs. Dexamethasone was a potent inhibitor of
      PAF- induced eosinophil accumulation, but higher doses of dexamethasone were
      required to inhibit IL-5-induced eosinophilia. LPS-induced neutrophilia was less
      sensitive to the inhibitory effects of dexamethasone, than PAF-induced
      eosinophilia. Both LPS- and TNF alpha-induced neutrophilia were inhibited by the
      same doses of dexamethasone. In contrast, higher doses of dexamethasone were
      required to inhibit CINC-induced neutrophilia. Since data in the literature show
      that PAF-induced eosinophilia in guinea-pig lungs is dependent on the generation
      of IL-5, it is concluded that inhibition of this response, by dexamethasone, is
      due to inhibition of release of IL-5. Similarly, although data in the literature
      show that LPS-induced neutrophilia is dependent on the generation of TNF alpha,
      it is concluded that inhibition of this response, by glucocorticoids, is due to
      an action on an event which occurs after the release of TNF alpha, possibly
      through inhibition of chemokine release.

PMID- 8741006
TI  - Increased desensitization by picomolar phorbol ester of the endothelium-mediated
      effect of histamine in the perfused rat mesenteric bed.
AB  - The vasodilatatory, endothelium-mediated, effect of histamine (H), through H1
      receptor, in the isolated and perfused mesenteric bed of the rat, undergoes
      strong desensitization during perfusion or repetitive injections of noradrenaline
      (NA) and H. The mesenteric bed completely desensitized to H is responsive to
      carbachol (C) and this latter compound does not affect the H desensitization. The
      homologous desensitization to C effect is very small, attaining less than 10%
      after 30 min of continuous perfusion. In this work the effect of inhibitors or
      activators of protein-kinase(s)-C (PKC) are studied during continuous perfusion
      of H or C in preparations preconstricted by NA. Staurosporine antagonizes the
      onset of the H desensitization, while the rate of desensitization in increased by
      phorbol-12-myristate-13-acetate (PMA). PMA, at a concentration from 10(-12) to
      10(-10)M, selectively enhances the homologous desensitization of H, while at 10(
      8)M it also produces a desensitization to C. At least two different PKC
      isoenzymes might be involved in the desensitization of the vasodilatatory effect
      of H and C in the isolated and perfused rat mesenteric bed.

PMID- 8741007
TI  - The role of mast cell-derived histamine in the closure of an in vitro wound.
AB  - We have previously reported that mast cells (MC) stimulate 3T3 fibroblast
      migration and proliferation into an in vitro model of wound obtained by producing
      in a confluent 3T3 monolayer, a midline cut and by scraping the cells from half
      of the monolayer. The purpose of the present study was to determine the
      contribution of mast cell-derived histamine to this MC increasing effect.
      Histamine levels in supernatants of MC/ 3T3 cultures unactivated or activated
      with either compound 48/80 or anti-IgE antibodies (10 min) did not correlate to
      the degree of fibroblast migration and proliferation into the wound space (42 h).
      Various concentrations of histamine were added to 3T3 fibroblast monolayers in
      the absence of cocultured MC, and fibroblasts beyond the wound line were counted
      (42 h). Addition of 100 ng/ml histamine had the highest stimulating effect on
      fibroblast numbers. This effect was abrogated by the addition of cimetidine (an H
      2 antagonist). Addition of cimetidine to unactivated MC/ 3T3 cultures did not
      affect the increasing activity of MC presence on the wounded monolayer, although
      it diminished the enhancing effect obtained after MC activation with compound
      48/80. These results indicate that histamine is partially responsible for the
      mast cell enhancing effect on fibroblast migration and proliferation in an in
      vitro model of wound.

PMID- 8741008
TI  - Dextran sulfate sodium (DSS) induced experimental colitis in immunodeficient
      mice: effects in CD4(+) -cell depleted, athymic and NK-cell depleted SCID mice.
AB  - Administration of dextran sulfate to mice, given in the drinking water results in
      acute or subacute colonic inflammation, depending on the administration protocol.
      This colonic inflammation exhibits ulceration, healing and repair, and a
      therapeutic response that makes it valuable for the study of mechanisms that
      could act in the pathogenesis of human ulcerative colitis, a disease thought to
      have an immunologically dependent pathogenesis. To investigate if immunological
      mechanisms were involved in the induction of colonic inflammation in this model,
      mice with different degrees of immunodeficiency were used. It was shown that
      dextran sulfate induced colitis could be induced in Balb/c mice depleted of
      CD4(+) helper T cells by treatment with monoclonal antibodies preceded by adult
      thymectomy. The depletion of CD4(+) was verified by flow cytometric analysis.
      Furthermore, the colonic inflammation could equally be induced in athymic CD-1
      nu/nu mice lacking thymus-derived T cells, in T and B-cell deficient SCID mice,
      and also in SCID mice depleted of NK cells by treatment with anti-asialo GM1
      antibodies. The NK-cell depletion was verified by measuring spleen NK-cell
      activity. The resulting colonic inflammation in all these types of deficient mice
      was qualitatively comparable, as shown by clinical and histological appearance.
      These results indicate that the presence of functional T, B and NK cells is not
      crucial for the induction of dextran sulfate colitis in mice.

PMID- 8741009
TI  - Involvement of leukotrienes in allergic pleurisy in actively sensitized rats:
      inhibition by the lipoxygenase inhibitor T-0757 of the increase in vascular
      permeability and leukotriene E4 production.
AB  - The relative contributions of inflammatory mediators to the increase in vascular
      permeability in antigen-induced pleurisy were examined in rats actively
      sensitized with ovalbumin. The effects of various inhibitors were assessed on the
      exudate volume and plasma exudation rate in the pleural cavity. Two peaks were
      observed in plasma exudation rate at 0.5 and 3 h after antigen challenge. At 0.5
      h, there was a marked decrease in the histamine content of the pleural cells and
      also a sharp increase in the LTE4 level in the exudate, which was inhibited dose
      dependently by the lipoxygenase inhibitor T-0757. Indomethacin and cyproheptadine
      both depressed exudate volume and exudation rate, whereas T-0757 only reduced the
      exudation rate. At 3 h, a substantial LTE4 concentration was still detected in
      the exudate, and the exudation rate was depressed by T-0757 and indomethacin, but
      not by cyproheptadine. These results suggest that histamine is involved mainly in
      the early phase, and leukotrienes predominantly contribute to the later phase of
      exudation. Prostaglandins appear to be involved in both phases. Allergic pleurisy
      of rats, therefore, may be a suitable model to examine the roles of these
      inflammatory mediators.

PMID- 8741010
TI  - Augmented plasma and tissue kallikrein like activity in synovial fluid of
      patients with inflammatory articular diseases.
AB  - We studied some of the components of the kininogen-kallikrein-kinin system,
      simultaneously, in plasma and synovial effusions of patients with inflammatory
      articular diseases. Plasma and tissue kallikrein like activity and kininogen
      levels were evaluated. Active plasma and tissue kallikreins in plasma and
      synovial fluid were detected by their amidase activity upon specific chromogenic
      substrates. Kininogen levels were determined by a bioassay. Both specific amidase
      activity of plasma and tissue kallikreins were augmented in synovial effusions in
      relation to their own plasma activity. Kininogen levels in synovial fluid tended
      to be diminished in relation to plasma, however statistical significance was not
      reached. The consumption of kininogen is probably related to kinin production.
      This finding together with increased activities of plasma and tissue kallikreins
      reinforce the involvement of kinins in pathogenesis of inflammatory articular
      diseases.

PMID- 8741011
TI  - Additive effect of nitric oxide and prostaglandin-E2 synthesis inhibitors in
      endotoxin-induced uveitis in the rabbit.
AB  - The involvement of nitric oxide (NO) and prostaglandin E2 (PGE2) was investigated
      in a model of intraocular inflammation induced by intravitreal injection of
      endotoxin (lipopolysaccharide, LPS, 10 ng) in rabbits. The severity of uveitis,
      the myeloperoxidase (MPO) activity in iris-ciliary body, and the protein
      concentration in aqueous humor were determined. Nitric oxide synthase (NOS) and
      cyclooxygenase (COX) activities were assessed respectively by nitrite and PGE2
      levels in aqueous humor. Treatment with inhibitors of NOS (NG-nitro-L-arginine
      methyl ester, L-NAME, 50 mg/kp i.p.) or COX (diclofenac, 30 micrograms,
      topically), alone or in combination, were compared to a saline-treated group.
      Diclofenac or L-NAME alone reduced or delayed the intensity of uveitis, and
      partially decreased the protein concentration in aqueous humor; diclofenac, but
      not L-NAME, partially reduced the polymorphonuclear leukocyte infiltration in the
      iris ciliary body as indicated by the MPO activity. Treatment with both
      inhibitors in combination diminished the clinical uveitis, the disruption of the
      blood-aqueous barrier and the MPO activity in the iris-ciliary body. We conclude
      that NO and PGE2 have additive effects in endotoxin-induced uveitis in rabbits,
      and that the inhibition of both pathways would improve the therapeutical
      management of uveitis.

PMID- 8741012
TI  - Exogenous nitric oxide stimulates mucin secretion from LS174T colonic
      adenocarcinoma cells.
AB  - The effect of exogenous and endogenous nitric oxide on the secretion of mucins
      from the human colonic adenocarcinoma cell-line LS174T was studied. Mucin
      secretion was followed by measuring the release of [3H]-glucosamine metabolically
      labelled glycoproteins eluted in the void volume of Sepharose 4B column
      chromatography. In response to exogenously produced nitric oxide from sodium
      nitroprusside, mucin secretion occurred in a time- and dose-dependent fashion
      that preceded epithelial cell damage. However, in the presence of the nitric
      oxide scavenger myoglobin, mucin secretion and cell damage were abrogated.
      Endogenously produced nitric oxide did not affect mucin secretion as the addition
      of excess L-arginine, the substrate for nitric oxide synthase, the removal of
      arginine from the culture medium with arginase or the inhibition of nitric oxide
      synthase with the competitive inhibitor NG-monomethyl-L-arginine had no effect on
      basal mucin release. These results suggest that exogenously produced nitric oxide
      can directly affect mucin secretion as a cytoprotective mechanism.

PMID- 8741013
TI  - Conformational and receptor-binding properties of the insect neuropeptide
      proctolin and its analogues.
AB  - Proctolin (Arg-Tyr-Leu-Pro-Thr) was the first insect neuropeptide to be
      chemically characterised. It plays an essential role in insect neurophysiology
      and is involved in muscular contraction and neuromodulation. Elements of
      secondary structure in solution have been studied by comparing data obtained from
      NMR and molecular dynamics simulations. Different secondary structural
      requirements are associated with agonist and antagonist activities. A favoured
      conformation of proctolin has an inverse gamma-turn, comprising an intramolecular
      hydrogen bond near the C-terminal end between Thr NH and Leu CO. Antagonists have
      a more compact structure resembling a 'paperclip' loop, containing an
      intramolecular hydrogen bond between Tyr NH and Pro CO, possibly stabilised by a
      salt bridge between the N- and C-terminal groups. A cyclic analogue retains
      antagonist activity and resembles a beta-bulge loop, also comprising
      intramolecular hydrogen bonds between Tyr NH and Pro CO and Thr CO. These models
      may offer feasible starting points for designing novel compounds with
      proctolinergic activity.

PMID- 8741014
TI  - Structure-activity analysis of fluorinated 1-N-arylamino-1-arylmethanephosphonic
      acid esters as inhibitors of the NADH:ubiquinone oxidoreductase (complex I).
AB  - The structural and electronic properties of fluorinated 1-N-arylamino-1
      arylmethanephosphonic acid esters were studied and related to the inhibitory
      effects on NADH:ubiquinone oxidoreductase (complex I). Electrostatic potential
      surfaces, dipole moments and molecular geometries were analysed. Based on the
      conformational analysis and the electronic parameters, a simple model for the
      active site of the fluorinated 1-N-arylamino-1-arylmethanephosphonic acid esters
      was developed, explaining the inhibitory power. The strongest inhibition effects
      were found for the 1-(N-4-trifluoromethoxyphenyl)-amino-1-phenylmethanephosphonic
      acid diethyl ester 1bab.

PMID- 8741015
TI  - On the electrostatic and steric similarity of lactam compounds and the natural
      substrate for bacterial cell-wall biosynthesis.
AB  - Electrostatic and structural properties of a set of beta-lactam, gamma-lactam and
      nonlactam compounds have been analyzed and compared with those of a model of the
      natural substrate D-alanyl-D-alanine for the carboxy- and transpeptidase enzymes.
      This first comparison of the electrostatic properties has been based on a
      distributed multipole analysis of high-quality ab initio wave functions of the
      substrate and potential antibiotics. The electrostatic similarity of the
      substrate and active compounds is apparent, and contrasts with the electrostatic
      properties of the noninhibitors. This has been quantified to give a reasonable
      correlation with the MIC (Minimum Concentration for Inhibition) and with kinetic
      data (k2/K) in accordance with the model for interaction of the lactam compounds
      with DD-peptidase. These correlations provide a better prediction of
      antibacterial activity than purely structural criteria.

PMID- 8741016
TI  - Orientational sampling and rigid-body minimization in molecular docking
      revisited: on-the-fly optimization and degeneracy removal.
AB  - Strategies for computational association of molecular components entail a
      compromise between configurational exploration and accurate evaluation. Following
      the work of Meng et al. [Proteins, 17 (1993) 266], we investigate issues related
      to sampling and optimization in molecular docking within the context of the DOCK
      program. An extensive analysis of diverse sampling conditions for six receptor
      ligand complexes has enabled us to evaluate the tractability and utility of on
      the-fly force-field score minimization, as well as the method for configurational
      exploration. We find that the sampling scheme in DOCK is extremely robust in its
      ability to produce configurations near to those experimentally observed.
      Furthermore, despite the heavy resource demands of refinement, the incorporation
      of a rigid-body, grid-based simplex minimizer directly into the docking process
      results in a docking strategy that is more efficient at retrieving experimentally
      observed configurations than docking in the absence of optimization. We
      investigate the capacity for further performance enhancement by implementing a
      degeneracy checking protocol aimed at circumventing redundant optimizations of
      geometrically similar orientations. Finally, we present methods that assist in
      the selection of sampling levels appropriate to desired result quality and
      available computational resources.

PMID- 8741017
TI  - Modeling lipophilicity from the distribution of electrostatic potential on a
      molecular surface.
AB  - Molecular lipophilicity L is represented as a function of four surface
      electrostatic potential descriptors: L = f(B+F, B-F, B+R, B-R). Each B descriptor
      is computed from the products of elements of molecular surface area, delta(si),
      and the molecular electrostatic potential (MEP), V(ri), at the center of an area
      element: B = sigma(i) delta(si) V(r(i)). Octanol-water partition coefficients
      (P(ow)) are correlated with these four surface-MEP descriptors: log P(ow) = c0 +
      c1B+F + c2B-F + c3B+R + c4B-R. Good correlations are obtained for homologous
      series of aliphatic alcohols, amines and acids, as well as for a set of aromatic
      compounds with various functional groups. Within this approach, we find that the
      molecular fragment contributions of surface-MEP descriptions to log P are
      approximately additive. We have computed the values for the following fragments: 
      CH2-, -CH3, _COOH, -OH and -NH2. These contributions can be used to estimate the
      molecular lipophilicity and partition coefficients of new compounds, without
      additional quantum-mechanical calculations. The proposed approach provides a
      reasonably accurate tool that can be useful in quantitative structure-activity
      relations for computer-aided rational drug design. More importantly, the
      correlation model is conceptually simpler than previous work in the literature
      and can be improved systematically.

PMID- 8741018
TI  - Structure-activity correlation study of HIV-1 inhibitors: electronic and
      molecular parameters.
AB  - Quantitative structure-activity relationships (QSARs) for 40 HIV-1 inhibitors, 1
      [(2-hydroxyethoxy)-methyl]-6-(phenylthio)thymine and its derivatives, were
      studied. Fully optimized geometries, based on the semiempirical AMl method, were
      used to calculate electronic and molecular properties of all compounds. In order
      to examine the relation between biological activities and structural properties,
      multiple linear regression models were employed. A suitable QSAR model was
      obtained, showing not only statistical significance, but also predictive ability.
      The significant molecular descriptors used were atomic charges of two substituted
      carbon atoms in the thymine ring, hydration energies and molar refractivities of
      the molecules. These descriptors allowed a physical explanation of electronic and
      molecular properties contributing to HIV-1 inhibitory potency.

PMID- 8741019
TI  - The coordination of the catalytic zinc in alcohol dehydrogenase studied by
      combined quantum-chemical and molecular mechanics calculations.
AB  - The coordination number of the catalytic zinc ion in alcohol dehydrogenase has
      been studied by integrated ab initio quantum-chemical and molecular mechanics
      geometry optimisations involving the whole enzyme. A four-coordinate active-site
      zinc ion is 100-200 kJ/mol more stable than a five-coordinate one, depending on
      the ligands. The only stable binding site for a fifth ligand at the zinc ion is
      opposite to the normal substrate site, in a small cavity buried behind the zinc
      ion. The zinc coordination sphere has to be strongly distorted to accommodate a
      ligand in this site, and the ligand makes awkward contacts with surrounding
      atoms. Thus, the results do not support proposals attributing an important role
      to five-coordinate zinc complexes in the catalytic mechanism of alcohol
      dehydrogenase. The present approach makes it possible also to quantify the strain
      induced by the enzyme onto the zinc ion and its ligands; it amounts to 42-87
      kJ/mol for four-coordinate active-site zinc ion complexes and 131-172 kJ/mol for
      five-coordinate ones. The four-coordinate structure with a water molecule bound
      to the zinc ion is about 20 kJ/mol less strained than the corresponding structure
      with a hydroxide ion, indicating that the enzyme does not speed up the reaction
      by forcing the zinc coordination sphere into a structure similar to the reaction
      intermediates.

PMID- 8741020
TI  - Computer simulation of the binding of amonafide and azonafide to DNA.
AB  - Intercalative binding of the antitumor drugs amonafide and azonafide to the
      oligonucleotide duplex d(GGCCGGCCGG).d(CCGGCCGGCC) was compared using molecular
      dynamics in vacuum with the AMBER force field. A number of reasonable possible
      binding conformations were obtained, with the azonafide complexes favored over
      the amonafide complexes in net binding enthalpy. In comparison with amonafide,
      the larger chromophore of azonafide permits greater DNA distortion and wider side
      chain swings, without falling out of the intercalation site. The best model
      obtained was used for further dynamics on amonafide and azonafide with solvent
      and counterions present, and again the azonafide complex had a more favorable
      enthalpy. Furthermore, the enthalpy change on going from solvent into the
      intercalation site was less unfavorable for azonafide. These results are
      consistent with the stronger DNA binding of azonafide compared to amonafide, as
      observed in relative melting transition temperature increases and tumor
      inhibition in cell cultures.

PMID- 8741021
TI  - Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients
      suffering from mild to moderate primary degenerative dementia of the Alzheimer
      type or multi-infarct dementia.
AB  - The efficacy of the ginkgo biloba special extract EGb 761 in outpatients with
      presenile and senile primary degenerative dementia of the Alzheimer type (DAT)
      and multi-infarct dementia (MID) according to DSM-III-R was investigated in a
      prospective, randomized, double-blind, placebo-controlled, multi-center study.
      After a 4-week run-in period, 216 patients were included in the randomized 24
      week treatment period. These received either a daily oral dose of 240 mg EGb 761
      or placebo. In accordance with the recommended multi-dimensional evaluation
      approach, three primary variables were chosen: the Clinical Global Impressions
      (CGI Item 2) for psychopathological assessment, the Syndrom-Kurztest (SKT) for
      the assessment of the patient's attention and memory, and the Nurnberger Alters
      Beobachtungsskala (NAB) for behavioral assessment of activities of daily life.
      Clinical efficacy was assessed by means of a responder analysis, with therapy
      response being defined as response in at least two of the three primary
      variables. The data from the 156 patients who completed the study in accordance
      with the study protocol were taken into account in the confirmatory analysis of
      valid cases. The frequency of therapy responders in the two treatment groups
      differed significantly in favor of EGb 761, with p < 0.005 in Fisher's Exact
      Test. The intent-to-treat analysis of 205 patients led to similar efficacy
      results. Thus, the clinical efficacy of the ginkgo biloba special extract EGb 761
      in dementia of the Alzheimer type and multi-infarct dementia was confirmed. The
      investigational drug was found to be well tolerated.

PMID- 8741022
TI  - How to assess the onset of antidepressant effect: comparison of global ratings
      and findings based on depression scales.
AB  - The timing of clinical drug effects in depression can be estimated by a variety
      of methodological approaches, which might account for the heterogeneity of
      findings. We compared the patients' own ratings of the onset of antidepressant
      effect with onset estimations that were based on the intraindividual courses of
      depression as measured by the Hamilton Depression Rating Scale and a self-rating
      scale, the von Zerssen Adjective Mood Scale. The data of two control-group
      studies on brofaromine vs. imipramine were reanalyzed, the first, comprising 224
      non-elderly and the second 195 elderly patients. In both studies the patients
      rated a significantly earlier onset of activity (means: days 12 and 16) than any
      other method. The means of the scale-based ratings varied between days 20 and 31
      and showed a marked dependence on the response criteria selected: strict response
      criteria produced later onset estimations than less strict ones. Whereas the
      patient's own ratings indicated a significantly later onset of activity in the
      elderly patients, none of the scale-based measures supported this difference. The
      discussion focuses on the importance of methodological aspects.

PMID- 8741023
TI  - Efficacy and safety of an opiate sigma-receptor antagonist (SL 82.0715) in
      schizophrenic patients with negative symptoms: an open dose-range study.
AB  - The psychotomimetic effects of opiate agonists/antagonists led to the hypothesis
      that opiate sigma receptors could be involved in the etiology of schizophrenia.
      This assumption is supported by animal trials with selective sigma-receptor
      antagonists. SL 82.0715 is a substance with a highly selective affinity for sigma
      receptors. To clarify the question whether it improves negative symptoms of
      schizophrenia, ten chronic schizophrenic patients with a predominant negative
      symptomatology were examined and treated with increasing doses (2.5 - 10.0 mg/d).
      Psychopathology was evaluated weekly using the PANSS, BPRS, and CGI, side-effects
      were assessed by the HAS and the S/A scale. Four patients showed improvement of
      negative symptoms (two slight, two marked improvement), two patients deteriorated
      as regards the positive symptomatology, psychopathology in the other patients did
      not change. The tolerability of SL 82.0715 was very good, no extrapyramidal side
      effects occurred. To further evaluate the therapeutic efficacy, open studies with
      a larger number of patients and/or double-blind studies are necessary.

PMID- 8741024
TI  - Psychopharmacological drugs as represented in the press: results of systematic
      analysis of newspapers and popular magazines.
AB  - The representation of mental diseases and psychopharmacological drugs in the
      media, especially in the press, is thought to be of great impact on people's
      opinions on the subject. During the course of one year, all articles about
      psychopharmacological drugs and cardiac drugs published in nineteen German
      newspapers were collected. All statements, together with related aspects, reasons
      for prescription, individual details of the patient, effects and side-effects,
      were registered and classified according to a key. The results show that, in
      contrast to 13% of the articles about cardiac drugs, half of the reports about
      psychopharmacological drugs deal primarily with the problems of side-effects and
      dependence the drugs may produce. There was much more critical comment and
      emotional emphasis used to characterize the psychopharmacological drugs. Only in
      9% of articles was their therapeutic efficacy mentioned. Cardiac drugs are
      generally discussed objectively in a medical context and in 53% efficacy is
      emphasized. Psychopharmacological drugs are often mentioned in stories about
      prominent persons having a life crisis, taking drugs, turning to alcoholism, or
      in the context of social decline. Only in 3% of all articles about
      psychopharmacological drugs was it possible to identify a serious mental disease
      as the reason for prescription. The reasons for and implications of these
      findings, which mainly reflect the negatively biased image of
      psychopharmacological drugs in women's magazines (while they are treated
      relatively fairly in general newspapers) are discussed.

PMID- 8741025
TI  - Subchronic antidepressant treatment with venlafaxine or imipramine and effects on
      blood pressure and heart rate: assessment by automatic 24-hour monitoring.
AB  - Venlafaxine is a new nontricyclic antidepressant inhibiting the reuptake of
      serotonin, noradrenaline, and, to a lesser extent, dopamine without antagonizing
      cholinergic, histaminergic, or noradrenergic receptors. Significantly, in a first
      placebo-controlled safety and efficacy study, high doses of venlafaxine increased
      blood pressure in some study subjects. In order to investigate further the effect
      of subchronic antidepressant drug treatment on blood pressure and heart rate, the
      effects of a conventional tricyclic (imipramine) and a structurally different
      phenethylamine antidepressant (venlafaxine) were compared. Sixteen inpatients
      with major depression (melancholic type) were treated for six weeks with
      imipramine or venlafaxine in a randomized parallel double-blind design. Blood
      pressure was monitored for 24 hours before treatment and at days 14 and 28 by
      means of a portable, automatic blood-pressure monitoring system. Both compounds
      lowered systolic blood pressure by about 5% on average, while diastolic pressure
      was influenced neither by imipramine nor by venlafaxine. Imipramine treatment
      resulted in a significant 15% increase in heart rate on both day 14 and day 28,
      whereas heart rate tended to decrease under venlafaxine. When the data of
      individual patients were evaluated, a clinically significant increase in blood
      pressure was apparent in one venlafaxine-treated patient; a marked increase in
      blood pressure in one patient treated with imipramine proved to be reversible
      with continued treatment. Due to the relatively small sample sizes, the present
      data do not allow a definitive judgement as to whether venlafaxine may cause
      differential blood pressure alterations in comparison with imipramine. However,
      our results demonstrate that the blood pressure-increasing effect reported for
      venlafaxine from first clinical studies might be clinically significant in
      individual patients. Furthermore, our study shows that 24-hour monitoring of
      blood pressure and heart rate is a powerful tool in safety evaluations of new
      drugs, even in relatively small samples.

PMID- 8741026
TI  - Hepatic failure associated with imipramine therapy.
AB  - Imipramine is an antidepressant drug that is rarely associated with mild liver
      function abnormalities. These are usually minor and transient liver enzyme
      elevations which return to normal levels upon discontinuation of the drug. We
      describe a 48-year-old male who developed subfulminant hepatic failure after
      imipramine usage, with complete recovery within three months after
      discontinuation of the drug.

PMID- 8741027
TI  - Mirtazapine as treatment for serotonin syndrome.

PMID- 8741028
TI  - Albright's hereditary osteodystrophy.

PMID- 8741029
TI  - Migration and child health: the Dutch experience.
AB  - Nearly one million of the fifteen million inhabitants of the Netherlands are
      directly descending from migrant parents. Of these inhabitants, 75% come from
      former colonies (Surinam and the Netherlands Antilles) and Mediterranean
      countries like Turkey and Morocco. The mortality rate of Turkish and Moroccan
      children under 15 years of age is two to three times higher compared to Dutch
      children. Main causes are perinatal death (including congenital malformations),
      accidents and drowning, infectious diseases and death during holidays in the
      country of origin. Inequalities in health between the migrant and Dutch children
      are demonstrated in several surveys conducted at both national and local levels.
      Apart from socio-economic differences, this can be attributed to three main
      causes; different pathology due to imported infectious diseases or inherited
      disorders, different life style and socio-cultural factors. The cumulative factor
      explains the differences in health, comparable with several other countries in
      Europe where migrants from Mediterranean countries and former colonies live.
      CONCLUSION: Migration has an increasing impact on the daily practice of Dutch
      paediatricians as well as elsewhere in Europe. Inclusion of intercultural and
      international aspects of health in the curriculum of the medical paediatric
      education is paramount.

PMID- 8741030
TI  - Treatment variables as predictors of intellectual outcome in children with
      congenital hypothyroidism.
AB  - The purpose of this study was to assess how much of the variance in intellectual
      outcome at 2 and 6 years of age could be attributed to treatment variables in
      children with congenital hypothyroidism, and which of the parameters used for
      monitoring treatment predicted later development. Forty-five children, early
      treated according to general recommendations, were studied. Linear multiple
      regression analysis was used, controlling for socio-economic status and the
      pretreatment serum thyroxine concentration. At 2 years of age, 19% of the
      variance in Mental Development Index (Bayley Scales of Infant Development) was
      attributed to treatment variables: combinations of serum thyroxine and serum TSH
      during the 1st year and bone age at mean age 1.5 years (mean z-scores). At 6
      years of age, 35% of the variance in Verbal IQ (Wechsler Preschool and Primary
      Scale of Intelligence) was attributed to treatment variables: 13% to the mean
      serum thyroxine concentration during the 1st year, 12% to the initial L-thyroxine
      dose per kilogram body weight per day, and 10% to a combined measure for serum
      thyroxine and serum TSH during the 2nd year (mean z-score). CONCLUSION: Both the
      initial L-thyroxine dosage and treatment variables during the 1st and the 2nd
      year (serum thyroxine, serum TSH and bone age) predicted later intellectual
      outcome in children with congenital hypothyroidism.

PMID- 8741031
TI  - Catch-up growth after prolonged hypothyroidism.
AB  - This report presents an analysis of four patients who suffered from longstanding
      untreated hypothyroidism, with special attention to the phase of catch-up growth
      after the start of L-thyroxine treatment. Although a permanent height loss could
      not be prevented, the capacity to establish a remarkable catch-up growth spurt
      proved to be still intact, even after a long period of thyroid dysfunction.
      CONCLUSION: Catch-up growth in hypothyroidism may be incomplete if treatment has
      been started shortly before or during puberty.

PMID- 8741032
TI  - Growth and development in thalassaemia major patients with severe bone lesions
      due to desferrioxamine.
AB  - Nine transfusion-dependent beta-thalassaemia major patients (seven males and two
      females), aged 4-15 years, with growth retardation and severe rickets-like
      radiological lesions due to continuous subcutaneous chelation therapy with
      desferrioxamine (45-75 mg/kg body weight, 6-7 time/week), were seen in our centre
      during the last 8 years. Serum ferritin levels ranged from 976 to 4115
      micrograms/l. There was a progressive decline in growth velocity in these
      patients 2-3 years before the appearance of rickets-like radiological lesions.
      All patients underwent surgery to correct genu valgum and/or slipped capital
      epiphyses. The final height was below the 3rd percentile in six patients (SDS:
      from -2.9 to -5.2). The short stature was mainly due to a disproportion between
      upper and lower segments. Six of the patients had an associated sensorineural
      hearing loss. CONCLUSION: Our data emphasize the importance of an accurate
      surveillance of the toxic effects of desferrioxamine treatment and warn of the
      risk of overtreating patients with low iron overload and also suggest a possible
      individual idiosyncrasy to the adverse effects of chelation therapy.

PMID- 8741033
TI  - Mobilization of tumour cells during biopsy in an infant with Ewing sarcoma.
AB  - Ewing sarcoma and the closely related peripheral primitive neuroectodermal
      tumour, recently referred to as Ewing tumour (ET), are characterised by unique
      gene rearrangements on chromosome 22. The breakpoints have been cloned and shown
      to fuse the Ewing sarcoma gene to one of two closely related ETS proto-oncogens,
      FLI-1 or ERG, which reside on chromosomes 11 and 21, respectively. The
      rearrangement results in the expression of specific hybrid transcripts which can
      be detected with high sensitivity by the reverse transcriptase polymerase chain
      reaction technique (RT-PCR) in primary tumours, blood and bone marrow. We report
      on a 7-month-old boy with a pelvic Ewing sarcoma in whom circulating tumour cells
      were identified in the peripheral blood during open tumour biopsy by RT-PCR.
      However, before and 6 days after surgery no tumour cells could be detected in the
      peripheral blood. CONCLUSION: The application of RT-PCR to monitor shedding of
      tumour cells during surgical intervention will help to evaluate if open biopsy
      potentially contributes to metastatic tumour cell spread.

PMID- 8741034
TI  - Evaluation of cortical thickness and bone density by roentgen microdensitometry
      in growing males and females.
AB  - The bone mineral content (BMC) and the cortical thickness at the distal radius
      and at the II metacarpal were assessed in growing individuals (167 females and
      158 males) by radiometric and quantitative roentgen microdensitometric methods.
      BMC adjusted for age and pubertal status was significantly higher in males than
      in females. However, the BMC corrected for bone volume (volumetric bone density,
      g/cm3) and the metacarpal cortical index (cortical area/total area) were
      identical in males and females. BMC rose progressively with age, approaching a
      plateau by the end of puberty. Lower but still significant increases with age
      were also observed for volumetric bone density of the metacarpus and the
      metacarpal index. These increases were also most marked by the end of pubertal
      maturation and might be related to diminution of bone turnover. CONCLUSION: This
      study provides the normative data of bone mass in growing individuals by making
      use of a reasonably accurate and easily available technique. The results obtained
      indicate that most of the differences between males and females and the changes
      with age are related to changes in skeletal dimension rather than density.

PMID- 8741035
TI  - Surfactant therapy for respiratory failure due to near-drowning.
AB  - We report a nearly drowned 3-year-old boy who was treated successfully with
      exogenous bovine surfactant. Exogenous surfactant should be administered to
      patients with refractory respiratory failure based on the pulmonary
      pathophysiology in near-drowning.

PMID- 8741036
TI  - Goldenhar, Mobius and hypoglossia-hypodactyly anomalies in a patient: syndrome or
      association?
AB  - The Mobius, Goldenhar and hypoglossia-hypodactyly anomalies are usually sporadic
      conditions with a recurrence risk of about 2%. The combination of Goldenhar and
      one or the two others is rare, whereas the concomitant occurrence of Mobius and
      hypoglossia-hypodactyly, and/or Poland, and/or Klippel-Feil anomaly is well
      known. Pathogenetically, vascular disruptions around the 4th embryonic week have
      been hypothesized. In vivo and pathological studies as well as animal models
      support this theory for all the above-mentioned combinations. Whether a preceding
      blastogenetic alteration is an influencing factor or a disorganization mutation,
      remains unclear. We describe a 3-year-old girl with bilateral anotia, epidermoid
      on the right eye, 6th and 7th nerve palsy, hypoglossia, left hypodactyly, and
      ventricular septal defect. CONCLUSION: We wish to emphasize the aetiological
      relevance of vascular disruptions in this previously unreported combination of
      Mobius, Goldenhar and hypoglossia-hypodactyly anomalies. The concurrence of
      anomalies in this patient represents an association and not a pleiotropic
      syndrome.

PMID- 8741037
TI  - Co-existence of Dubowitz and hyper-IgE syndromes: a case report.
AB  - A case of a 5-year-old girl is described whose clinical features included
      postnatal growth retardation, microcephaly and characteristic facial appearance.
      These are recognized as the main features of the Dubowitz syndrome. Apart from
      these features, our patient had recurrent infections of the sinopulmonary tract,
      high serum IgE levels, defective chemotaxis of polymorphonuclear cells and
      defective antibody response, findings characterizing the hyper-IgE syndrome. The
      co-existence of these two syndromes is rare and we suggest that this is the first
      such case in the literature. CONCLUSION: Patients with the Dubowitz syndrome will
      Dubowitz syndrome will require long-term follow up because there is a
      considerable risk for the syndrome to co-exist with primary immunodeficiency or
      for malignancies to develop.

PMID- 8741038
TI  - Three missense mutations in the galactose-1-phosphate uridyltransferase gene of
      three families with mild galactosaemia.
AB  - Classical galactosaemia caused by deficiency of galactose-1-phosphate
      uridyltransferase (GALT) is characterized by acute symptoms of hepatocellular
      dysfunction, sepsis, cataracts and failure to thrive. Galactose limitation
      reverses these complications immediately, however, most of these children have a
      long-term complication of verbal dyspraxia mental retardation and ovarian
      failure. The GALT gene was cloned and several mutations including the common
      Q188R have been reported. In this study the coding region of GALT was amplified
      by polymerase chain reaction from genomic DNA of classical galactosaemic
      individuals and characterized by direct sequencing of the products. Three
      missense mutations were identified in three patients with a mild galactosaemic
      variant: (1) replacement of threonine-138 by methionine (T138M); (2) replacement
      of arginine by tryptophan (R259W); and (3) replacement of threonine by alanine
      (T350A). All three galactosaemic individuals, one girl and two boys, have varying
      degrees of residual GALT activity in RBC and their galactose-1-phosphate levels
      decreased much faster than in other galactosaemic patients. These missense
      mutations occur in regions that are not highly conserved domains. CONCLUSION: The
      study of the molecular basis related to the phenotype variation may indeed help
      to prognosticate the outcome of patients with classical galactosaemia.

PMID- 8741039
TI  - Atypical vitamin B12-unresponsive methylmalonic aciduria in sibship with severe
      progressive encephalomyelopathy: a new genetic disease?
AB  - We report on two siblings, a girl of 7 years and a boy of 2 years, who presented
      in infancy with hypotonia, athetoid movements, myopathy and severe developmental
      delay. The progressive clinical course was characterized by ophthalmoplegia,
      pyramidal tract signs, loss of visual contact and failure to thrive. The older
      sister died at the age of 7 years. The younger brother followed an almost
      identical clinical course. MRI of the brain revealed bilateral hypodensities and
      atrophy of the putamen. Neurophysiological investigations were consistent with
      peripheral neuropathy. Investigations for neurometabolic disorders in urine,
      plasma and CSF of both patients revealed a consistent increase of methylmalonic
      acid in urine, plasma and CSF as well as borderline low free GABA in CSF. Except
      for an inconstant elevation of lactate in the boy, metabolic acidosis,
      hypoglycaemia, episodic ketoacidosis, or hyperammonaemia, the usual concomitants
      of organoacidopathies, were absent in both children. Homocystinuria was excluded.
      Methylmalonic aciduria did not respond to antibiotic treatment, vitamin B12
      therapy nor dietary protein restriction. Incorporation of [14C]propionate into
      protein in cultured fibroblasts was pathologically but inconsistently decreased.
      Both patients' cell lines showed only minimal response to hydroxocobalamin and
      normal methylmalonyl-CoA mutase activity. CONCLUSION: Even though the definitive
      underlying enzymatic defect in this sibship remains obscure our results suggest a
      new genetic disorder. This report illustrates that hitherto undescribed metabolic
      disorders remain to be elucidated even in long investigated areas of intermediary
      metabolism such as methylmalonic aciduria.

PMID- 8741040
TI  - Pentoxifylline reduces plasma tumour necrosis factor-alpha concentration in
      premature infants with sepsis.
AB  - Increased plasma tumour necrosis factor alpha (TNF) concentration correlates with
      mortality in sepsis. We suggested that pentoxifylline (PTXF), which is known to
      inhibit TNF production, may improve survival and attenuate clinical symptoms of
      sepsis in neonates. Plasma TNF levels were evaluated in 29 newborn infants with
      sepsis. Patients were randomly assigned into two groups, receiving PTXF in a dose
      of 5 mg/kg per hour for 6 h or placebo (saline), on 3 successive days. Both
      groups were subjected to the same conventional therapy. TNF was evaluated before
      and after PTXF or placebo administration on the 1st and 3rd days of therapy.
      There was a statistically significant decrease in plasma TNF level in the PTXF
      group when the values before the first and after the last PTXF infusion were
      compared [mean: 671.5 pg/ml; SD: 438; med: 729.6 vs mean: 41.0 pg/ml; SD: 64.1;
      med: 11.5; P < 0.000004]. In the placebo group, decrease was not significant
      [mean: 633.0 pg/ml SD: 488.6; med: 618.9 vs 246.9 pg/ml; SD: 243.9; med: 191.0].
      A significantly higher plasma TNF level, evaluated after the last PTXF infusion,
      was found in the placebo group [246.9 pg/ml vs 41.0 pg/ml; P < 0.001]. Only one
      of four infants with signs of shock in the placebo group survived, whereas all of
      five newborns with symptoms of shock in the PTXF group survived [P < 0.04]. An
      increased incidence of metabolic acidosis [P < 0.05], necrotizing enterocolitis
      [P < 0.04] and renal insufficiency [P < 0.05] was observed in infants in the
      placebo group. CONCLUSION: PTXF inhibits production of TNF and may have
      therapeutic value in the treatment of premature infants with sepsis complicated
      by shock.

PMID- 8741041
TI  - Docosahexaenoic and arachidonic acid content of serum and red blood cell membrane
      phospholipids of preterm infants fed breast milk, standard formula or formula
      supplemented with n-3 and n-6 long-chain polyunsaturated fatty acids.
AB  - The contents of docosahexaenoic (DHA) and arachidonic acid (AA) of plasma and red
      blood cell membrane phospholipids were studied in 41 very low birth weight
      infants fed either breast milk (n = 18), a standard formula without long-chain
      polyunsaturated fatty acids with 20 or 22 carbon atoms (LCP) but with alpha
      linolenic acid and linoleic acid (n = 11) or a formula additionally supplemented
      with n-3 and n-6 LCP in relations typical for human milk (n = 12) after 2, 6, and
      10 weeks of feeding. The content of DHA and AA in plasma phospholipids declined
      in the infants fed the LCP-free formula but remained more or less constant during
      the whole feeding period in those infants fed breast milk as well as in those fed
      the LCP-supplemented formula. The differences between the group fed the LCP-free
      standard formula and the two groups fed LCP-containing diets became significant
      during the first 2 weeks of feeding. In contrast, there were no differences
      between the group fed breast milk and the group fed the supplemented formula
      during the study period. Similar effects could be observed regarding the
      composition of red blood cell membrane phospholipids, but the differences between
      the infants fed the LCP-free standard formula and the two other groups with LCP
      containing diets were significant only for AA. The data indicate that very low
      birth weight infants are unable to synthesize LCP from alpha-linolenic acid and
      linoleic acid in sufficient amounts to prevent a decline of LCP in plasma and red
      blood cell phospholipids. Additionally, the data show, that supplementation of
      formulas with n-3 and n-6 LCP in amounts typical for human milk fat results in
      similar fatty acid profiles of plasma and red blood cell membrane phospholipids
      as found during breast milk feeding. CONCLUSION: Supplementation of formula with
      long-chain polyunsaturated fatty acids improves the LCP status of very low birth
      weight infants.

PMID- 8741042
TI  - Pesticides in baby food: a European issue.

PMID- 8741043
TI  - Case of the month: a 14-month-old girl with persistent wheezing. Aspirated
      foreign body.

PMID- 8741044
TI  - Resistance of Bifidobacteria and Lactobacilli to tobramycin.

PMID- 8741045
TI  - Early surgery of the intestinal tract in infants--a possible risk factor for
      subsequent latex allergy?

PMID- 8741046
TI  - Dextromethorphan in molybdenum cofactor deficiency.

PMID- 8741047
TI  - Haemangioendothelioma in a preterm infant associated with highly elevated alpha
      fetoprotein.

PMID- 8741048
TI  - Successful treatment of a recurrent large cystic hygroma in a child with
      intracystic injection of OK-432.

PMID- 8741049
TI  - 5-alpha reductase deficient men are fertile.

PMID- 8741050
TI  - Transition from latent to overt hypoparathyroidism in a child with CATCH 22.

PMID- 8741051
TI  - Statistical correlation between increased TSH and increased gliadin antibodies in
      Down syndrome.

PMID- 8741052
TI  - Ethics in scientific publication--fraud, redundancy and errors.

PMID- 8741053
TI  - Skeletal 3-D CT: advantages of volume rendering over surface rendering.
AB  - Both surface rendering and volume rendering have been extensively applied to CT
      data for 3-D visualization of skeletal pathology. The review illustrates
      potential limitations of each technique by directly comparing 3-D images of bone
      pathology created using volume rendering and surface rendering. Surface rendering
      show gross 3-D relationships most effectively, but suffer from more stairstep
      artifacts and fail to effectively display lesions hidden behind overlying bone or
      located beneath the bone cortex. Volume-rendering algorithms effectively show
      subcortical lesions, minimally displaced fractures, and hidden areas of interest
      with few artifacts. Volume algorithms show 3-D relationships with varying degrees
      of success depending on the degree of surface shading and opacity. While surface
      rendering creates more three-dimensionally realistic images of the bone surface,
      it may be of limited clinical utility due to numerous artifacts and the inability
      to show subcortical pathology. Volume rendering is a flexible 3-D technique that
      effectively displays a variety of skeletal pathology with few artifacts.

PMID- 8741054
TI  - The bicipital groove of the humerus: sonographic and radiographic correlation.
AB  - OBJECTIVE: The objective of this study was to compare ultrasonography (US) and
      plain radiography in the evaluation of the bicipital groove of the humerus and to
      determine the accuracy of US in measurement of the width and depth of the groove
      compared to plain radiography. PATIENTS AND METHODS: Visualization of the groove
      and its abnormalities in 350 consecutive patients by US and on tangential groove
      radiographs were compared. The groove was measured prospectively in 45 patients
      on the ultrasound imaging monitor and retrospectively on groove radiographs
      without knowledge of the US results. RESULTS: The bony anatomy of the groove was
      adequately seen with US in 90% of patients (314 of 350) and on groove radiographs
      in 91% (319 of 350). All 24 shallow and 6 tunnel-shaped grooves were diagnosed
      with both imaging methods, but osteophytes and erosions could not be reliably
      demonstrated with US. CONCLUSION: Sonography was as accurate for evaluation of
      the dimensions of the bicipital groove as groove radiographs, and both methods
      had a similar failure rate. Pathological changes of the walls of the groove could
      not be reliably evaluated with sonography.

PMID- 8741055
TI  - Ultrasonography for diagnosis of rotator cuff tear.
AB  - In this study the clinical usefulness of ultrasonography in the diagnosis of
      rotator cuff tears was assessed. One hundred twenty-two patients undergoing
      preoperative ultrasonography were evaluated surgically. Three different
      ultrasonographic machines were applied with a 7.5-MHz linear-array transducer.
      Surgery confirmed a sensitivity of 79% for full-thickness tears and 50% for
      partial thickness tears. In 73 patients with negative ultrasonographic findings,
      the specificity was 100% for full-thickness tears and 90% for partial-thickness
      tears. The diagnostic sensitivity for full-thickness tears of the Hitachi EUB-340
      system was significantly lower than those of Hitachi EUB-415 and EUB-515, and
      thus the former cannot be recommended for detection of rotator cuff tears. The
      sensitivity with regard to partial-thickness tears was also significantly lower
      with the Hitachi EUB-340 system as compared to the Hitachi EUB-515. There were no
      significant differences in false-positive rate among the three machines used. In
      conclusion, accurate ultrasonographic diagnosis of rotator cuff tear requires a
      high-resolution machine, as well as considerable experience in interpretation.

PMID- 8741056
TI  - Variations in morphology of the lumbosacral junction on sagittal MRI: correlation
      with plain radiography.
AB  - OBJECTIVE: To identify on sagittal magnetic resonance imaging (MRI) scans of the
      lumbar spine the features that indicate the presence of a lumbosacral
      transitional vertebra (LSTV). DESIGN: One hundred consecutive sagittal T1-and T2
      weighted MRI scans of the lumbar spine were reviewed and separated into four
      types depending upon the absence or presence of disc material between what was
      considered to be the uppermost sacral segment and the remainder of the sacrum, as
      follows: type 1: no disc material present; type 2: a small residual disc, not
      extending for the whole anteroposterior (AP) diameter of the sacrum; type 3: a
      well-formed disc extending for the whole AP diameter of the sacrum; type 4: a
      well-formed disc extending for the whole AP diameter of the sacrum with, in
      addition, an abnormal upper sagittal sacral outline. The corresponding plain
      radiographs of each patient were than reviewed and assessed for the presence of
      an LSTV. These were classified according to the method of Castellvi et al.
      PATIENTS: All patients had been referred for MRI of the lumbar spine, usually
      because of back pain with or without radiculopathy. There were 51 male and 49
      female patients with a mean age of 42 years and an age range of 18-85 years.
      RESULTS AND CONCLUSIONS: With regard to sacral morphology on MRI, 30 patients had
      type 1, 42 patients type 2, 16 patients type 3 and 12 patients type 4 morphology.
      Fifteen patients had an LSTV. There was a good correlation between the presence
      of a fused LSTV and a type 4 MRI appearance, indicating that this type of LSTV
      can be identified on sagittal MRI scans.

PMID- 8741057
TI  - Radiological prevalence of lumbar intervertebral disc calcification in the
      elderly: an autopsy study.
AB  - OBJECTIVE: The objective of this study was to investigate the in vitro
      radiological prevalence of lumbar intervertebral disc calcification (IDC) in the
      elderly and its relation to osteoarthritis (OA). MATERIALS AND METHODS: Lumbar
      spine segments comprising L2-4 were resected from 60 cadavers (30 males, 30
      females; average age 67 years) and investigated with high-contrast radiography
      and computed tomography (CT). RESULTS AND CONCLUSIONS: IDC was found in 58.3% of
      the patients using high-contrast radiography and in 46.7% of the patients using
      CT. IDC prevalence and OA grades in the lumbar spine and right hand were found to
      increase with age. IDC prevalence and OA grades for L2-3 were not significantly
      different from those for L3-4. No significant sex difference was found for IDC
      prevalence and OA grades. The results indicate that IDC is significantly
      underestimated in vivo by conventional radiography and the intervertebral disc
      calcification may be a common phenomenon in aging. The exact relation IDC to OA
      remains undetermined.

PMID- 8741058
TI  - Computed tomography of the normal sternoclavicular joint.
AB  - OBJECTIVE: The objective of this work was to establish a reference population for
      the study of the sternoclavicular joint (SCJ). DESIGN: A prospective study of the
      SCJ was carried out by high-resolution computed tomography (CT). CT images were
      read by two radiologists and two rheumatologists using a pre-established grid (27
      elementary signs). PATIENTS: Sixty healthy subjects, homogeneously distributed by
      sex and decade of life, from 20 to 80 years old, were studied. RESULTS AND
      CONCLUSIONS: The main results were the following: 98% of healthy subjects
      presented at least one sign; mean number of signs per subject was 2.4 +/- 1.9;
      mean number of signs was higher ( P < 0.005) in men (mean = 3.1 +/- 2.1) than in
      women (mean = 1.7 +/- 1.3); number of signs increased with age (P < 0.001). Some
      signs were very frequent: "ossification of the first costal cartilage" (88%),
      "Surrounded subchondral clavicular erosion" (27%). Some signs were significantly
      more frequent in the elderly: "sternal osteophyte" after the age of 70 (P < 0.01)
      and "meniscal calcification" (P < 0.01) and "sternal subchondral sclerosis" (P <
      0.05) after the age of 60. The number of clavicular signs was greater than that
      of sternal signs (P < 0.001). These results can be used as references for the
      study of the SCJ.

PMID- 8741059
TI  - Relationship of elongated anterior tubercle to incomplete segmentation in the
      cervical spine.
AB  - PURPOSE: To describe the elongated anterior tubercle of cervical vertebrae, its
      association with incomplete segmentation, and its analogy to sacralization of the
      lower lumbar vertebrae. MATERIALS AND METHODS: Cases with elongated anterior
      tubercles of the cervical vertebrae detected on plain radiography were collected
      during routine practice and their features analyzed on plain radiography and MR
      imaging. Five patients, aged 19-40 years, with the anomaly seen on plain
      radiography were included in this study. MR imaging was undertaken in one
      patient. RESULTS: Hypertrophy of the anterior tubercle was associated with
      incomplete segmentation in three of the five patients. Oblique views were
      adequate to demonstrate its nature. CONCLUSIONS: The association of an elongated
      tubercle and incomplete segmentation is similar to partial sacralization at the
      lumbosacral junction. Clinically it is important that these anomalies are not
      mistaken for pathologic findings.

PMID- 8741060
TI  - Technical note: CT scout views of the cervical spine in severely head-injured
      patients.
AB  - The objective of this study was the validation of a CT multiprojection scout view
      method for the evaluation of cervical spine integrity in severely head-injured
      patients. Following brain CT, 130 consecutive patients underwent anteroposterior,
      laterolateral, and 45 degrees right and left oblique scout views of the cervical
      spine. The method allowed direct and prompt detection of traumatic lesions of the
      cervical spine in ten cases without moving the patients from the scanner table.

PMID- 8741061
TI  - Association between diffuse idiopathic skeletal hyperostosis (DISH) and multiple
      myeloma.

PMID- 8741062
TI  - Cost-effectiveness of ultrasonographic screening for congenital hip dysplasia in
      new-borns.
AB  - OBJECTIVE: Screening for congenital dysplasia of the hips (CDH) of new-borns,
      mostly by Ortolani's of Barlow's tests, is widely performed, but nevertheless
      dysplasias are still discovered late. Ultrasonographic screening has been
      reported to reduce the number of these cases. The present investigation is
      intended to evaluate the cost-effectiveness of such as screening programme.
      MATERIALS AND METHODS: The cost of performing ultrasound investigations at
      Haukeland Hospital and the treatment costs of late-discovered CDH were calculated
      on the basis of 26 cases of late-discovered CDH at Hagavik Orthopaedic Hospital.
      Figures for sensitivity and specificity were taken from the literature. RESULTS:
      General ultrasonographic screening programmes for CDH will not be cost-effective
      because the population screened will be too large and the demands upon
      sensitivity too high. However, investigating babies at risk is probably cost
      effective. CONCLUSION: A CDH screening programme requires high sensitivity and
      one should preferably aim at screening babies at risk. In Norway a centralisation
      to larger hospitals may therefore be necessary.

PMID- 8741063
TI  - Multifocal vascular lesions of bone: imaging characteristics.
AB  - OBJECTIVE: Multifocal vascular processes which arise in bone are a very
      inhomogeneous class of diseases. Four of these processes are derived from
      endothelial precursors, however, and share a similar radiographic spectrum. These
      four entities are reviewed in order to clarify their imaging patterns and the
      diagnostic utility of imaging modalities. METHODS: Eight cases of cystic
      angiomatosis, multifocal hemangioma, hemangioendothelioma and angiosarcoma
      presenting to a tertiary referral center over a 7-year period were reviewed. The
      medical literature was also reviewed for information concerning the imaging of
      these processes. RESULTS: All four diseases produced radiolucent defects on plain
      radiographs with variable margination reflecting the aggressiveness of the
      lesions. Computed tomography was used to examine five patients and provided
      supportive, though generally non-diagnostic, information in the five cases in
      which it was performed. Radionuclide bone scintigraphy, as reported in the
      literature, underestimated the extent of skeletal involvement in all eight cases,
      though some lesions were identified. Radionuclide imaging with labeled red blood
      cells, performed in three cases, did not add any information, which is contrary
      to some reports in the literature. Magnetic resonance imaging proved the most
      sensitive for identifying lesions, although the imaging characteristics were not
      diagnostic. CONCLUSIONS: Plain radiographs are the mainstay for imaging
      multifocal endothelial processes. Radiographs provide information on
      aggressiveness, multifocality and distribution of lesions. Computed tomography
      provides similar information. Magnetic resonance imaging often detects additional
      lesions. The insensitivity of radionuclide bone scintigraphy is surprising.
      Reports of unique deposition of radionuclide in tagged red blood cell scanning
      has been reported to support the diagnosis of vascular lesions, but it did not do
      so in these cases.

PMID- 8741064
TI  - Osseous metaplasia associated with amyloid-producing plasmacytoma of bone: a
      report of two cases.
AB  - Amyloid-producing plasmacytoma of bone is a rare myeloma variant. We describe two
      patients with plasmacytomas of bone with extensive amyloid deposition and
      metaplastic bone formation which can be confused on imaging with osteosarcoma.
      Histologic confirmation was obtained in both cases. Metaplastic new bone
      formation was identified within these lesions and appears to be responsible for
      the radiographic appearances.

PMID- 8741065
TI  - Congenital fusion of the fourth and fifth metacarpals associated with primary
      gonadal failure.
AB  - Congenital fusion of the fourth and fifth metacarpals is described in a male
      infant and his maternal grandfather. Primary gonadal failure, which is present in
      the infant, has not been noted in previously, reported cases. The pedigree in
      this family is compatible with X-linked recessive or autosomal dominant
      inheritance with incomplete penetrance.

PMID- 8741066
TI  - Calcific tenosynovitis associated with calcific myonecrosis of the leg: imaging
      features.
AB  - The findings with histologically proven calcific tenosynovitis of the tibialis
      anterior tendon associated with calcific myonecrosis are described. This case
      emphasizes the typical appearance of this unusual relationship such as peripheral
      plaque-like calcifications of the tendon sheath, fluid-calcium levels,
      presentation as painless mass, and calcification and liquefaction of muscle
      bundles.

PMID- 8741067
TI  - Osteonecrosis of the femoral condyles following traumatic dislocation of the
      knee.

PMID- 8741068
TI  - Sinus histiocytosis with massive lymphadenopathy: MRI findings of osseous
      lesions.
AB  - The case of a 20-year-old female with SHML and osseous involvement is presented.
      We describe three different patterns of involvement in the diametaphyseal
      portions of the long bones with similar MRI signal characteristics.

PMID- 8741069
TI  - Lipoblastoma of the foot.
AB  - Lipoblastoma is an uncommon benign lipomatous soft tissue mass of childhood,
      occurring most commonly in children less than 3 years of age. We present a case
      of lipoblastoma occurring in the foot of a 14-year-old boy and review the
      literature. The appearance of the mass on magnetic resonance imaging (MRI) is
      illustrated and is correlated with the findings at gross and microscopic
      pathological examination. A lobulated architecture, the presence of adipose
      tissue, thin nonenhancing septa, peripheral lobules of more immature and
      therefore less specific tissue, and a peripheral pseudocapsule were evident on
      MRI and at pathological examination.

PMID- 8741070
TI  - Cystic angiomatosis: case report and review of the literature.
AB  - The objective of this article was to offer a better characterization of the
      typical clinical presentation, radiologic findings, histology, treatment
      approaches, and differential diagnosis of cystic angiomatosis, a rare condition
      of which previous reports have been confusing because of unclear diagnostic
      criteria, different classifications, and variations in terminology. A case report
      using the improved imaging techniques of computed tomography scanning is
      presented in addition to an analysis and review of the previous literature, which
      relied heavily on plain film radiography, biopsy, and necropsy for diagnosis. A
      case report of a 26-year-old man initially symptomatic at age 12 is presented.
      Although a rare condition, cystic angiomatosis must be considered in pediatric
      and young adult patients presenting with diffuse, multifocal, cystic skeletal
      lesions, with or without visceral involvement.

PMID- 8741071
TI  - Idiopathic progressive osteolysis of craniofacial bones.
AB  - We present the case report of a diabetic 51-year-old male, who presented with
      painless mobilization of the superior incisor teeth. The X-ray study showed
      osteolysis, without any soft tissue mass, in craniofacial and orbital bones. In
      the control X-ray studies performed during the 2 years' evolution, a progressive
      increase in the intensity and extension of the osteolysis was observed. The
      diagnosis of progressive idiopathic osteolysis is one of exclusion, based mainly
      on clinico-radiological findings, evolution and compatible histological findings.

PMID- 8741072
TI  - Hemorrhagic prepatellar bursitis.
AB  - Simple prepatellar bursitis is easily diagnosed both clinically and by MRI. MRI
      shows the typical T1 and T2 lengthening of fluid within the bursa. However,
      because of complex MRI appearance of hemorrhage, chronic hemorrhagic bursitis and
      the size of the prepatellar mass the clinical and MRI appearance can be very
      different.

PMID- 8741073
TI  - Ewing's sarcoma of the sacrum.
AB  - A lytic lesion with soft-tissue extension in the sacrum of a 47-year-old man was
      needle-biopsied under computed tomographic (CT) guidance using an 18-gauge
      cutting needle. The cytologic appearance of the lesion and immunohistochemical
      staining were diagnostic of Ewing's sarcoma. Specifically, a new marker (O13) for
      the presence of glycoprotein p30/32 mic2 in Ewing's sarcoma was utilized.

PMID- 8741074
TI  - Fat necrosis.
AB  - We report the MR appearance of a case of subcutaneous fat necrosis, which is a
      previously unreported etiology for knee mass. The role of MR imaging in
      differentiating fat necrosis from other causes of soft tissue masses is
      discussed. We conclude that MR characteristics of subcutaneous fat necrosis are
      typical and allow its differentiation from other types of soft tissue lesions.

PMID- 8741075
TI  - Carcinoma and the peripheral nervous system.
AB  - An underlying carcinoma is an important differential diagnosis in peripheral
      neuropathy. While direct compression and infiltration of spinal roots or
      peripheral or cranial nerve trunks or branches can be identified easily when they
      occur in association with established malignancy, their diagnosis when they are
      presenting features may be difficult. In paraneoplastic sensory neuronopathy
      autoantibodies to neuronal antigens have become useful diagnostic markers for an
      underlying carcinoma, especially anti-Hu antibodies. Strong circumstantial
      evidence suggests that these antibodies form part of an autoimmune response which
      is responsible for the pathogenesis of some of these syndromes. Neuropathy
      appearing during the course of treatment of carcinoma may be due to radiation
      induced damage or the neurotoxic effects of some chemotherapeutic agents.
      Neurotrophic factors are being investigated as a strategy for reducing the
      neurotoxic effects of these agents.

PMID- 8741076
TI  - Fluctuating parkinsonism: a pilot study of single afternoon dose of levodopa
      methyl ester.
AB  - Thirty-four patients with idiopathic fluctuating Parkinson's disease and early
      afternoon "delayed on" or severely resistant "off" periods, in spite of long-term
      antiparkinsonian therapy, were studied. The first afternoon levodopa
      administration was substituted with an equimolar dosage of the liquid formulation
      levodopa methyl ester (LDME). The major end-points for efficacy were latency to
      "on" and duration of "on" periods. The patients were divided into five subgroups
      according to their baseline treatment and they were evaluated monthly for 6
      months using the Unified Parkinson's Disease Rating Scale. The patients completed
      weekly self-evaluation using an "on-off" chart. LDME was well tolerated by all
      the patients. A statistically significant reduction in latency to "on" was
      observed in all patients. The clinical effect of LDME remained stable during the
      treatment period (repeat measures ANOVA). The more rapid clinical effect of LDME
      and its stable and predictable antiparkinsonian activity represents a new and
      useful approach for treating patients with complicated Parkinson's disease.

PMID- 8741077
TI  - Ineffective leftward search in line bisection and mechanisms of left unilateral
      spatial neglect.
AB  - We examined the eye-fixation pattern of a patient with severe left unilateral
      spatial neglect who showed leftward searches of various extent in more than half
      of line bisection trials. Because of complete left homonymous hemianopia, he
      perceived only the segment of the line between its right endpoint and the point
      of the leftmost fixation. In the trials with leftward searches, he frequently
      placed the subjective midpoint on the right part of the perceived segment. In the
      trials without leftward searches, he placed it near the left extreme point of the
      perceived segment. For all these bisections, the subjective midpoint was
      constantly placed far to the right of the true midpoint of the line irrespective
      of the length perceived. We consider that in severe left unilateral spatial
      neglect, rightward attentional bias is the predominant factor that determines
      where to place the subjective midpoint. Transient attentional shift to the left
      may produce leftward searches, but it does not induce effective processing of
      line bisection.

PMID- 8741078
TI  - Sensory involvement in X-linked spino-bulbar muscular atrophy (Kennedy's
      syndrome): an electrophysiological study.
AB  - Electrophysiological findings were studied in a family with spino-bulbar muscular
      atrophy (SBMA): the subjects were three male patients aged 58, 38 and 34 years
      and two female carriers aged 63 and 28 years. Diagnosis was proven at the
      molecular genetic level. Electromyography in the males showed spontaneous
      activity and neurogenic reorganization of the motor unit; motor nerve conduction
      was normal. Sensory action potentials were variably reduced in amplitude, but
      some were completely normal. Somatosensory evoked potentials, from both the upper
      and lower limbs, were invariably abnormal because involvement of the central
      pathways was observed. These findings are in agreement with histological
      investigations documenting lesions in the posterior columns. Brain-stem acoustic
      evoked potentials showed an increase in wave I latency. The electrophysiological
      data provide further evidence of the extent of sensory damage either in the
      central or the peripheral nervous system in SBMA patients, who otherwise have a
      constant clinical presentation of progressive motor neuron disease.

PMID- 8741079
TI  - Diversity of intrathecal antibody synthesis against HTLV-I and its relation to
      HTLV-I associated myelopathy.
AB  - The humoral immune response against human T-cell lymphotropic virus type I (HTLV
      I) in the central nervous system (CNS) compartment and in the blood was
      investigated by enzyme immunoassay using 16 synthetic peptides corresponding to
      HTLV-I core and envelope sequences. We evaluated paired samples of cerebrospinal
      fluid and serum from HTLV-I seropositive Japanese patients, classified as
      follows: HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP; n =
      39), patients with spinal cord disease ascribed to either HAM/TSP or to some
      concomitant, HTLV-I-unrelated disease (possible HAM/TSP; n = 6) or carriers
      without any clinical signs of HAM/TSP (n = 15). HTLV-I-peptide-specific
      intrathecal antibody synthesis was found in 79% of HAM/TSP patients, but only in
      20% of carriers without HAM/TSP. The group of carriers without HAM/TSP showed
      local synthesis for some peptides (on average 0.3 peptides per patient). In most
      HAM/TSP patients, however, there was a diverse intrathecal immune response to
      several HTLV-I synthetic peptides (on average against 3.6 peptides per HAM/TSP
      patient), most frequently against gag p19 100-130, env gp21 458-488, and env gp46
      175-199 and 288-317. The intrathecal antibody synthesis against several HTLV-I
      determinants may represent a pathogenic immune response in HAM/TSP and is
      possibly related to the infiltration of virus-infected T-cells in the spinal
      cord.

PMID- 8741080
TI  - Survival in multiple system atrophy: a study of prognostic factors in 59 cases.
AB  - The various clinical features of multiple system atrophy (MSA) make the diagnosis
      of the disease difficult, especially in its early stages, when signs of
      differentiated neuroanatomical system involvement have not yet appeared.
      Mortality studies may be affected by the variability of the diagnostic criteria
      and selection bias. We used strict clinical and MRI criteria to diagnose MSA in
      59 patients. Patients with parkinsonian and cerebellar onset were compared.
      Median survival time from the onset of the first motor symptom was 7.5 years. Our
      results indicated a trend (P = 0.09) for the Northwestern University Disability
      Scale score to correlate with mortality, but we failed to find other
      characteristics identifying subgroups or predictors for survival.

PMID- 8741081
TI  - Feasibility of cognitive screening of patients with ischaemic stroke using the
      CAMCOG. A hospital-based study.
AB  - Brief screening tests would be convenient for the measurement of cognitive
      impairment in stroke patients. In these patients aphasia can interfere with test
      procedures. To evaluate the feasibility of examining cognitive functions in
      stroke patients we examined 129 patients with an ischaemic stroke using the
      CAMCOG, a standardised neuropsychological screening test, after an interval of at
      least 3 months. Most patients (88%) were able to complete the CAMCOG. Patients
      with severe aphasia were significantly more likely to have an abnormal CAMCOG
      score than patients without aphasia [relative risk (RR) 4.0, 95% confidence
      interval (CI) 2.8-5.8]. The group of patients with moderate aphasia was not at
      higher risk of having an abnormal CAMCOG score than patients without aphasia (RR
      1.4, 95% CI 0.6-2.8). Looking for other factors that might correlate with the
      scores, logistic regression analysis revealed age as the only significant factor
      for the prediction of the CAMCOG score (odds ratio 4.0, 95% CI 1.2-13.2). We
      concluded that the CAMCOG can conveniently be used for screening cognitive
      functions in patients with cerebral infarcts, even if there is moderate aphasia.

PMID- 8741082
TI  - Prednisone can protect against exercise-induced muscle damage.
AB  - In an experimental animal exercise model we tested whether daily administration
      of prednisone prevents the development of mechanically induced muscle fibre
      damage. Six-week-old rats were treated with different doses of prednisone ranging
      from 1 to 50 mg/kg body weight per day or with placebo, for 8 days. On day 6 of
      treatment the rats were forced to run for 2 h on a level treadmill. Two days
      after exercise morphological damage in the soleus muscles was quantified using
      light microscopy and a semi-automatic image analysis system. Creatine kinase (CK)
      activity was measured before exercise (day 5) and directly after exercise (day
      6). The expression of dystrophin in a placebo group and in a group that received
      5 mg prednisone/kg body weight per day with and without performing exercise was
      studied with Western blotting. The effect of prednisone on fibre type
      distribution was determined with an antibody against fast myosin and the effect
      of prednisone on the proliferative activity of muscle satellite cells was studied
      using bromodeoxyuridine (BrdU) immunohistochemistry. Exercise-induced muscle
      fibre damage varied in a dose-dependent way. In the placebo group the mean (SEM)
      damaged muscle fibre area was 4% (1%). The groups that received low doses of
      prednisone, 1 or 2.5 mg/kg per day, showed a similar level of muscle damage.
      However, with 5 mg prednisone/kg per day the amount of muscle fibre damage [mean
      (SEM)] was significantly reduced to 1.4% (0.5%) (P <or= 0.05, Student's t-test).
      High doses of prednisone had no protective effect. Directly after exercise the CK
      activity was increased two-fold, except in the group that received 50 mg
      prednisone/kg body weight per day. No changes in the amount of dystrophin were
      found after densitometric analysis of the Western blots. Prednisone did not
      affect the fibre distribution or the labelling index of satellite cells. We
      conclude that prednisone, given in an appropriate dose, protects muscle fibres
      against the development of mechanically induced damage, possibly by stabilizing
      the muscle fibre membranes. This action may explain the beneficial effect of
      prednisone observed in Duchenne muscular dystrophy patients.

PMID- 8741083
TI  - Transient renal impairment in acute intracerebral haemorrhage.
AB  - Transient impairment of renal function was found in 30 of 78 patients with acute
      intracerebral haemorrhage (ICH). Patients with a history of renal disease,
      dehydration, nephrotoxic drugs or septicaemia were excluded. In the 1st week, the
      mean serum creatinine level was 3.4 (range 1.7-7.7) mg/dl, which returned to
      normal in 2-4 weeks. Employing multivariate stepdown logistic regression
      analysis, Glasgow Coma Scale score and pulse pressure were found to be
      significantly related to renal impairment manifesting with a raised serum
      creatinine level, whereas pupillary asymmetry was of borderline significance. An
      acute rise in intracranial pressure following ICH may result in sympathetic
      overactivity, which may account for the renal impairment observed in our
      patients.

PMID- 8741084
TI  - Reinnervation and recovery of muscle energetics after nerve section and surgical
      repair.

PMID- 8741085
TI  - Amantadine in parkinsonian patients unresponsive to levodopa: a pilot study.

PMID- 8741086
TI  - Cerebral metastases of an allogenic renal cell carcinoma in a heart recipient
      without renal cell carcinoma.

PMID- 8741087
TI  - Brain SPECT in anterior opercular syndrome due to a unilateral lesion.

PMID- 8741088
TI  - [Oto-vestibular symptoms in patients with temporomandibular joint dysfunction.
      Electromyographic study].
AB  - The authors analyse the otovestibular symptoms (acoupheny, muffled hearing,
      vertigo, hypoacusia, otalgia) present among other symptoms of craniomandibular
      dysfunctions. A number of hypotheses have been advanced regarding the
      etiopathogenesis of these symptoms, but all stem from three theories. The first
      theory is based on the possibility of a mechanical transmission of force from the
      temporomandibular joint to the middle ear by the discomalleolar ligament. Another
      theory hypothesises the possible direct irritation by the condyl on the
      auriculotemporal nerve. The most widely credited etiopathogenetic theory, which
      is examined in this study, is that the hypertone of the tensor muscle of the
      tympanum and the tensor muscle of the velum palatinum, which are innervated like
      the masticatory muscles of the mandibular branch of the trigeminal nerve is the
      effect of these same muscles' hypertone. A group of 53 adult patients was
      selected to verify this theory. All patients were receiving treatment for
      dysfunctions of the temporomandibular articulation. Initial data were collected
      relating to the prevalence of each of the otovestibular symptoms studied; each
      patient then underwent computerised electromyographic analysis while the right
      and lefthand masseter and temporal muscles were resting. All tests were performed
      by the same operator. When analysing the results, patients were divided into two
      groups: one group contained those patients who had no symptoms relating to the
      ear, and the other contained patients with at least one symptom relating to the
      ear. Moreover, the group of symptomatic patients was divided into subgroups of
      patients with 1, 2, 3, and 4 of the symptoms studied. The mean
      electromyographical values for each muscle examined were then compared. The
      following results were obtained: 67.9% of subjects examined presented at least
      one otovestibular symptom; the symptom that was most frequently found was the
      feeling of muffled hearing (41.5%), followed by otalgia and vertigo; the
      prevalence of otalgia was much lower (7.5%). The most interesting finding emerged
      from a comparison between electromyographical values in patients suffering from
      otovestibular symptoms and the asymptomatic group. There was no significant
      difference in this series between this two groups, and the mean
      electromyographical value was higher in the group of asymptomatic patients.

PMID- 8741089
TI  - [Fine needle aspiration in the cytologic diagnosis of swellings in the parotid
      and submandibular regions. Cytologic-histologic correlations in 49 cases].
AB  - Fine needle aspiration biopsy (FNAB) has been widely used for a number of years
      and offers considerable advantages in comparison to conventional surgical biopsy.
      A number of organs can be subject to this diagnostic procedure with good results,
      including the salivary glands. This paper aimed to compare the cytological
      diagnosis of biopsy material obtained using FNAB and the subsequent histological
      diagnosis formulated after surgery in 49 patients with swellings in the parotid
      or submandibular region who were referred to the Department of Anatomy and
      Pathological Histology in L'Aquila. Cytohistological concordance was present in
      87.7% of the cases in this series, a percentage that is in line with that
      reported by other authors. The most frequent causes of diagnostic error may be
      ascribed to moderate nodule size and/or the scanty material obtained not suitable
      for diagnosis. In this series all cases of malignant neoplasia were correctly
      diagnosed. In spite of the limitations of this method, the authors consider that
      it plays an important role in the preoperative diagnosis of salivary gland
      pathologies.

PMID- 8741090
TI  - [Oral lesions in Kaposi sarcoma: clinical and radiotherapeutic considerations].
AB  - The epidemic form of Kaposi's sarcoma is the most frequent tumor in sieropositive
      patients. Every part of the body including oral cavity is affected by these
      lesions. According to modern acknowledgement in treating oropharynge carcinoma,
      radiotherapy is used for management of oral Kaposi's sarcoma. This paper reports
      a study of 10 patients suffering from Kaposi's sarcoma correlated to AIDS (EKS)
      treated with radiotherapy and chemiotherapy, achieving good results, at the
      Istituto Nazionale per lo Studio e la Cura dei Tumori of Milan (Divisone di
      Radioterapia C) from 1988 to 1992. Treatment has been performed using linear
      accelerator (6 Mev) or Co 60 unity in order to reach the deepest layer of mucosa
      lesions. Radiotherapy schedule consisted of 150-200 cGy daily fractions given 5
      times/week (w) for 4-5 w in split-course.

PMID- 8741091
TI  - [Protective effect on enamel of ultra-micronized hydroxyapatite in combination
      with orthodontic composite cement. In vivo study].
AB  - In this work the authors have studied in vivo, the protective action of
      ultramicronized hydroxylapatite combined with a cement for orthodontic use. An
      etching gel with 30% acid orthophosphoric for 30'' has been put on a selected
      group of teeth to be extracted. Then some ultramicronized hydroxylapatite has
      been applied and some brackets or bands bonded with composite cement. Besides, on
      another group of teeth selected for the control, some brackets have been bonded
      with the traditional technique without hydroxylapatite. Some photographic
      rebuilts of the surface of the teeth to be analysed have been executed at
      scanning electron microscopy. Further observations have been executed at the
      aplanatic microscopy stereo to identify the possible macroscopic alterations. The
      hydroxylapatite proves to have a protective action on the enamel near the
      orthodontic bands or brackets, fixes with cement and subjected to the action of
      an acid.

PMID- 8741092
TI  - [Activation of the immune system in periapical infection. 1. Lympho-monocytoid
      and plasma cellular elements of reactive soft tissue cells].
AB  - The authors have carried out a study on the immunitary mechanisms which stimulate
      and avoid eventual alterations of infected periapex. Above all the aim of this
      first study has been the microscopic and ultrastructural valuation of the
      cellular components that characterize the process of chronic phlogosis of
      periradicular tissue, lymphocytes T and B, plasmacells and macrophages, and of
      those even more typical of the soft reactive tissues, fibroblasts and epithelial
      cells. It's just the interaction among these immunocompetent cells which
      determines the structural change of the periapical bone whose most common image
      of radiotransparence make it possible to diagnose the sufference of the pulpo
      periapical system.

PMID- 8741093
TI  - [Adenomatoid hyperplasia of the minor salivary glands. Report of a clinical
      case].
AB  - The authors describe a case of adenomatoid hyperplasia of a minor salivary gland.
      On the basis of the literature, they discuss the clinical, diagnostic and
      therapeutic aspects and dwell upon the value of the histologic examination as the
      only way to achieve a correct diagnosis, because the lesion cannot be clinically
      discriminated from the tumoral lesions.

PMID- 8741094
TI  - [Efficacy and tolerability 80 mg granulated ketoprofen lysine salt in
      posttraumatic orodental pain: double blind vs placebo study].
AB  - A randomized, double-blind parallel group, placebo-controlled study was carried
      out in order to evaluate the analgesic and antiin-flammatory activity of
      ketoprofen lysine salt as granular formulation. Sixty patients undergoing
      extraction of an impacted third molar were treated orally with 80 mg ketoprofen
      lysine salt sachet or placebo t.i.d. for 3 days. The inflammation related local
      signs (pain, flare, local heat and wheal) were evaluated by scores at 1th and 3th
      day of observation; to study the time-course of analgesic activity, pain
      intensity was evalauted by Visual Analogic-Scale (VAS) by Scott-Huskisson before
      and 0.30 minutes, 1, 2, 3, 4, 5, 6, 8 hours after the first administration.
      Ketoprofen lysine salt was significantly superior to placebo in reducing all
      inflmamtory signs and symptoms starting from the first day of treatment; the
      analgesic effect was evident already 30 minutes after administration.
      Investigator's and patient's global evaluations of efficacy resulted favourable
      for ketoprofen lysine salt in 96.6% and for placebo in 26.7%. The three adverse
      events reported were limited to gastric pyrosis (ketoprofen lysine salt, two
      patients; placebo one patient) and posed no problem to patient management. These
      data demonstrate the pronouced and rapid analgesic and antinflammatory activity
      of 80 mg ketoprofen lysine salt granular formulation in post-operative pain and
      inflammation associated with dental surgery.

PMID- 8741095
TI  - The polytene nucleus in morphological, cytochemical, and functional studies of
      messenger RNA transcription, processing, and transportation.

PMID- 8741096
TI  - In vivo bromodeoxyuridine labelling index, AgNOR protein expression and DNA
      content in human tumours.
AB  - The correlation between AgNOR (silver stained nucleolar organizer region) protein
      quantity and the percentage of S-phase cells was determined in 45 human tumours
      of different origin (28 from endometrium, 8 from cervix, 4 from ovary, 3 from
      larynx, 1 from rhinopharynx and 1 from tongue). AgNOR protein quantity was
      evaluated by image analysis on histological sections stained by the one-step
      silver staining method. S-phase cells were detected in histological sections with
      anti-bromo-deoxyuridine (BrdU) antibodies after in vivo BrdU infusion. The
      relationship between AgNOR protein and BrdU labelling index (LI) values was
      tested by linear regression analysis. A highly significant association of the two
      parameters was found (r = 0.78; p < 0.001), independent of the tumour type. DNA
      content of the 45 tumours was also determined by flow cytometry, and the DNA
      quantity was correlated with the kinetics data. Euploid tumours had a mean AgNOR
      protein area of 3.33 +/- 1.34 microns2 and a mean BrdU-LI of 10.78 +/- 8.94%,
      while in aneuploid tumours the mean AgNOR protein area was 4.78 +/- 1.78 microns2
      and the mean BrdU-LI 17.37 +/- 8.79%. Both AgNOR protein quantity and BrdU-LI
      were significantly higher in aneuploid than in euploid tumours (Student-t Test: p
      < 0.05 and p < 0.02 for AgNOR and BrdU values, respectively). However, despite
      this significant difference, a relevant overlap of AgNOR protein and BrdU-LI
      scores was found within both the aneuploid and euploid groups.

PMID- 8741097
TI  - Cytochemical localization of Na(+)-K(+)-adenosine triphosphate activity in the
      proximal convoluted tubule cells of the gerbil Meriones crassus.
AB  - The present work describes the cytochemical localization of Na(+)-K(+)-ATPase in
      the proximal convoluted tubule cells of the gerbil Meriones crassus. By using
      CeCl3 as capture agent, a fine, uniform reaction product was distributed mainly
      across the basolateral membranes and at the apical surface. This study provides
      evidence that the ATPase enzyme studied is actually Na(+)-K(+)-ATPase because
      acetate buffer (bleaching agent) had no decalcifying effect, nor did the
      subsequent application of levamisole, an inhibitor of alkaline phosphatase, which
      can hydrolize ATP. Such findings may serve to provide insights into the
      regulatory role of the Na(+)-K(+)-ATPase in intra-extra cellular balance in the
      basolateral membranes of the proximal convoluted tubule cells of this desert
      animal which show thick basal laminae with their membrane-bound bodies. However,
      there is a lack of knowledge regarding the transport function of the assayed
      enzyme and these bodies.

PMID- 8741098
TI  - Histochemical demonstration of acetylcholinesterase activity in human Meibomian
      glands.
AB  - The distribution of acetylcholinesterase activity in human Meibomian glands was
      evaluated using enzyme-histochemical methods. The butyrylcholinesterase (BuChE)
      inhibitor, tetraisopropyl pyrophosphoramide (iso-OMPA), was used to localize
      acetylcholinesterase (AChE) activity, the AChE inhibitor, 1,5-bis (4
      allyldimethylammoniumphenyl) pentan-3-one dibromide (BW284c51), was used to
      localize BuChE activity, and eserine was used to inhibit all cholinesterase
      activity in control incubations; the appropriate specific inhibitors for
      competing enzymic activities were added to the incubation medium. At the light
      microscopic level, acetylcholinesterase reaction product appeared as cytoplasmic
      brown deposits, often crystalline. A very dense accumulation of AChE-positive
      nerve fibers was seen in the form of a network around the acinar and the ductal
      tissue of the glands. No discrete nerve endings were observed, whereas a strong
      reaction was elicited in some fibers in close association with blood vessels.
      These observations suggest that the cholinergic system is involved in the
      regulation of the Meibomian glands secretory function.

PMID- 8741099
TI  - An immunohistochemical study of the endocrine pancreas of ducks.
AB  - Pancreatic tissue specimens of domestic ducks were fixed in PAF, paraformaldehyde
      and Bouin's fluid. Sections were immunohistochemically stained with antisera
      against insulin, glucagon, somatostatin and 5-hydroxytryptamine (5-HT).
      Immunoreactive cells were detected in both exocrine and endocrine pancreas. The
      endocrine cells were grouped into three islet types: A, B and mixed islets. A
      islets comprised glucagon, somatostatin and 5-HT immunoreactive cells. B islets
      showed insulin, somatostatin and 5-HT immuno-reactive cells. Mixed islets were
      composed of all four immunoreactive cytotypes. Using a double immunofluorescent
      technique, it was observed that 5-HT immunoreactivity was present in some of the
      glucagon and in some of the insulin immunoreactive cells. B islets were observed
      throughout the pancreas. A and mixed islets were more concentrated in the splenic
      lobe, and decreased in number in the other lobes. These results were compared
      with those obtained in other avian species.

PMID- 8741100
TI  - VIP-like immunoreactivity within neurons and perivascular neuronal processes of
      the human cerebral cortex.
AB  - Using indirect immunocytochemical techniques, neurons with VIP (Vasoactive
      Intestinal Polypeptide)-like immunoreactivity (ir) have been demonstrated in the
      human cerebral cortex of the parietal lobe. In all the cortical layers containing
      positive neurons, perivascular immunoreactive neuronal processes have been
      detected: in arterioles, they are located in the adventitial and smooth muscle
      layers; in capillaries, they establish tight anatomical relations with the
      endothelium-pericyte layer and the perivascular glial sheath. Bodies of positive
      neurons have also been seen adhering to capillary walls. The detection of
      perivascular VIP-like ir provides morphological evidence of the role played by
      this polypeptide in the regulation of the cerebral blood flow. Moreover, the
      relationships between immunoreactive neuronal processes and perivascular glia
      might corroborate the suggestion that VIP is involved in the functioning of the
      blood-brain barrier.

PMID- 8741101
TI  - The blood cells and haemopoiesis of Diplodus sargus L.: haematological values,
      cytochemistry and leukocytes' response to vaccine stimulation.
AB  - The treatment with antipiogenic and trivalent antiviral vaccines evokes in
      sargus' blood an increase of the neutrophilic granulocytes and an activation of
      the lymphocytes. By using cytochemical reactions for acid phosphatase and
      aliesterase, a population of lymphocytes, amounting to about 25%, which displays
      positive reactions has been identified. The immunocytochemical reactions used to
      identify the mammalian T and B-lymphocytes, such as rosetting test, immune
      localization of CD (Cluster of differentiation) and of sIg, were performed with
      the aim of better classifying the lymphocytes of sargus, even though the use of
      mammalian monoclonal CD antibodies cannot be considered a certain proof of such a
      presence. Moreover, cytochemical reactions have revealed the presence of
      lysosomal enzymes in neutrophils and the presence of peroxidase which
      characterize the eosinophils. Hemopoiesis takes place in the spleen and in the
      lymphomieloid tissue of the kidney.

PMID- 8741102
TI  - Glycoconjugate expression changes during Rana dalmatina early development.
AB  - Glycoconjugates are generally involved in cell adhesion and morphogenetic
      movements. To investigate their distribution and expression changes during
      amphibian development, several FITC-or HRP-labeled lectins were used in Rana
      dalmatina embryos and larvae. During gastrulation, WGA, ConA, HPA, GSA-I, PNA and
      RCA-I labeled either the envelopes on the perivitelline space-contained
      substances, while ectodermal cells and/or extracellular matrix were mainly
      labeled by WGA, GSA-I, DBA and LTA. In these structures fibronectin-like
      molecules were also found. ConA, HPA, RCA-I, SBA also labeled ectoderm, but with
      lower affinity. At larval stages, ectodermal derivatives, such as larval skin,
      central nervous system, eye and ear, were also strongly labeled by WGA, DBA and
      LTA, while the affinity to ConA, HPA, GSA-I, SBA, appeared less visible; the
      affinity sites to RCA-I and PNA were totally lacking. Fibronectin-like
      immunoreactivity was hardly present at the larval stages. These results point out
      that glycoconjugate expression changes in cell surface and in extracellular
      matrix might be developmentally regulated. For this reason the different
      glycoconjugates seem to play stage-specific roles in early development.

PMID- 8741103
TI  - Ultrastructural localization of IgM on B-lymphocytes of Diplodus sargus.

PMID- 8741104
TI  - Retinal dystrophies and genetic counselling.
AB  - Increased patient demand is leading to a corresponding increase in the need for
      informed genetic counselling in ophthalmic practice which requires refined
      diagnosis, and a detailed knowledge of molecular genetics. Accurate assessment of
      risk and visual potential in prospective children is becoming available for a
      range of retinal dystrophies allowing for more educated decisions to be made by
      parents.

PMID- 8741105
TI  - The Walker-Warburg or a new syndrome?

PMID- 8741106
TI  - Present state of the fetal alcohol syndrome.

PMID- 8741107
TI  - Norrie-Warburg syndrome: two novel mutations in patients with classical clinical
      phenotype.
AB  - Norrie-Warburg syndrome (NWS) is a rare X-linked disorder characterized by
      blindness, which is invariable, deafness and mental disturbances, which are
      present occasionally. We describe here two novel mutations, a missense mutation
      (C126S) and a 1-base pair insertion (insT466/T467), together with a recurrent
      mutation (M1V), found in patients presenting with the classical clinical
      phenotype of NWS. All three mutations are likely to result in prominent
      structural changes of the norrin protein.

PMID- 8741108
TI  - Midline craniofacial defects and morning glory disc anomaly. A distinct clinical
      entity.
AB  - A case with a severe midline craniofacial defect, comprising a midline cleft lip
      and palate with a sphenoethmoidal encephalocele, hypertelorism, bilateral
      dysplastic optic discs and agenesis of the corpus callosum is described. The
      optic discs are consistent with the spectrum of appearances seen in the Morning
      Glory Disc Anomaly (MGDA). This anomaly is usually a uniocular problem that may
      be rarely associated with craniofacial abnormalities. Despite this range of
      abnormalities this child was developing well with a specific motor delay at the
      age of eight months. Cases with similar midline craniofacial abnormalities from
      the literature are reviewed. This condition appears to be a distinct entity
      within the spectrum of frontonasal dysplasia.

PMID- 8741109
TI  - Full-field electroretinograms in infants with hereditary tapetoretinal
      degeneration.
AB  - Full-field electroretinograms were recorded from four infants (under the age of
      12 months), with different types of tapetoretinal degeneration. Some of these
      patients, appear to have normal fundi. This article stresses the clinical
      usefulness of evaluation with electroretinography in young children.

PMID- 8741110
TI  - Blepharo-cheilo-dontic (BCD) syndrome.

PMID- 8741111
TI  - Ultrasonic evaluation of microphthalmos and coloboma. A discussion of 3 cases,
      with emphasis on microphthalmos with orbital cyst.
AB  - Three cases of ophthalmic malformations are discussed from the standpoint of the
      usefulness of ultrasound evaluation, however with respectful reference to the
      revised classification of microphthalmos and coloboma presented by Warburg 1993.
      The main findings were, (case 1): microphthalmos with iris coloboma, unilateral
      posterior orbital cyst, and mental retardation, karyotype normal, consanguineous
      parents, (case 2) trisomy 13 with extreme microphthalmos and cheilo-gnatho
      palatoschisis, and (case 3) ringchromosome 14, posterior fundus colobomas, and
      malformation of the heart, with features corresponding to the CHARGE association.

PMID- 8741112
TI  - Severe microcornea with anterior segment malformation in a mother and her son.
AB  - A male infant with microcornea, anterior segment dysgenesis and congenital
      cataracts, but with a normal ocular posterior segment is reported. His mother
      also had extreme microcornea, no useful vision from birth, but had globes of
      grossly normal size.

PMID- 8741113
TI  - Ocular myopathy and mitochondrial DNA deletion. A presentation of seven
      identified Danish patients.
AB  - This paper summarizes the data on Danish patients with ocular myopathy and
      mitochondrial DNA deletion (delta mtDNA). To date, a single Danish patient
      harbouring delta mtDNA has been reported. In the present study we have identified
      seven additional ones and characterized the nature of their deletion, both
      qualitatively and quantitatively. All patients are sporadic cases each with a
      single deletion in the range of 2.3-78 kb, the delta mtDNA accounting for 10-75%
      of the total mtDNA in the biopsy analyzed. The clinical severity correlates with
      the percentage of deletion molecules, and not with the size of the deletion.

PMID- 8741114
TI  - Prenatal diagnosis of choroideremia.
AB  - With the mapping of the locus CHM for choroideremia and the subsequent cloning of
      the gene, reliable carrier and prenatal diagnosis has become a possibility. We
      discuss our experience with prenatal diagnosis of choroideremia, an X-linked
      choroidoretinal dystrophy leading to blindness in otherwise healthy males. In the
      period 1987-1995, five prenatal diagnoses have been performed by either indirect
      linkage analysis or by detection of the disease-causing mutation, reflecting the
      impact of molecular biology in clinical genetic practice.

PMID- 8741115
TI  - Ocular findings and sphenoid bone morphology in tuberous sclerosis.
AB  - The aim of the study was to focus on the correlation between the ocular findings
      and the morphology of the sphenoid bone supporting the optic nerve in patients
      with tuberous sclerosis. Ten patients participated in the investigation. The
      sphenoid bone morphology was analyzed from existing radiographs of the cranium.
      The results were compared to the individual ophthalmologic diagnosis. Changes in
      the midline osseous structure, the sella turcica and optic sulcus seem to be
      correlated with the severity of the ocular findings.

PMID- 8741116
TI  - The clinical and genetic heterogeneity of autosomal dominant cataract.

PMID- 8741117
TI  - Results of treatment of amblyopia with a screening program for early detection.
AB  - The Swedish program for early intervention in children with visual dysfunction,
      was evaluated with respect to the results of treatment of amblyopia. One hundred
      and seventy-two amblyopic children were examined before and at 6, 12 and 18
      months after the beginning of treatment. The mean visual acuity of the amblyopic
      eye was 0.76 and the mean ratio of visual acuity between the two eyes was 0.75 or
      better in all types of amblyopia. Children with strabismic amblyopia showed
      slightly poorer treatment results than the other types, in spite of the fact that
      their amblyopia had been detected earlier than the others. The results attest to
      the importance of careful screening of monocular visual acuity in all children,
      which in Sweden occurs at 4 years of age. This provides a good basis for
      detection and treatment of amblyopia. Only one child in the group had a visual
      acuity at 0.2 and may therefore be at risk for visual handicap if the better eye
      should be lost later in life.

PMID- 8741118
TI  - The cause of death in Laurence-Moon-Bardet-Biedl syndrome.
AB  - The certificates of death of 14 deceased patients with Laurence-Moon-Bardet-Biedl
      (LMBB) syndrome, in which retinal dystrophy is dominant feature, were review.
      Death occurred at a considerably younger age than in the general population.
      Renal disease was noted as primary or contributing cause of death in 7 cases with
      the diagnoses: cyst of the kidney, renal sclerosis, renal failure, proteinuria,
      renal disease unspecified and malignant hypertension with renal involvement. It
      is concluded that renal involvement is characteristic of individuals with LMBB
      syndrome and seems to reduce life expectancy considerably.

PMID- 8741119
TI  - Corneal deepithelialization caused by acute deficiency of isoleucine during
      treatment of a patient with maple syrup urine disease.
AB  - Classical Maple Syrup Urine Disease is a serious, autosomal recessive and rare
      metabolic disorder due to a completely inactive enzyme complex for metabolizing
      the branched amino acids leucine, valine and isoleucine. If untreated the disease
      is lethal. Metabolic control achieved by strict dietary treatment results in
      normal development. In this paper we describe deepithelialization of the cornea
      together with skin and intestinal symptoms as the result of isolated deficiency
      of isoleucine during treatment of a critically ill, newborn infant with this
      unusual disease.

PMID- 8741120
TI  - A syndrome with retinitis pigmentosa, progressive hearing impairment, vestibular
      dysfunction, and congenital cataract.
AB  - A family with an unusual association of retinitis pigmentosa, progressive and
      severe hearing impairment, vestibular dysfunction, and congenital zonular
      cataract is described. The disease had a rather uniform appearance in five
      affected individuals. Parental consanguinity was documented in all cases and a
      common ancestor born in 1702 was identified. Consequently, autosomal recessive
      inheritance seems to be the most likely mode of transmission. This disorder
      possibly represents a new clinical entity among combined retinal dystrophy and
      hearing impairment syndromes.

PMID- 8741121
TI  - Cranio-orbital teratoma.
AB  - A new-born baby presented with a large, rapidly growing tumour. The tumour
      involved the right orbit, the anterior half of the right intracranial space and
      extended through the skull of the temporal region. The proptotic eye ruptured due
      to exposure. The tumour was extirpated when the patient was 12 days old. A large
      recurrence was extirpated two months later. The tumour was firmly bound to the
      medial aspect of the superior orbital fissure which probably was the location of
      origin of the tumour. Based on the size of the intracranial-and the orbital part
      of the tumour, it was classified as a secondary orbital teratoma. The tumour was
      macroscopically composed of cystic and solid areas. Microscopically it was seen
      to be a benign teratoma with tissue from all three germinal layers.

PMID- 8741122
TI  - Contralateral temporal hypometabolism on positron emission tomography in temporal
      lobe epilepsy.
AB  - INTRODUCTION: No detailed case studies report lateralised hypometabolism on
      positron emission tomography (PET) contralateral to the epileptogenic focus in
      temporal lobe epilepsy (TLE). MATERIAL AND METHODS: We performed 18F
      fluorodeoxyglucose (FDG) PET in two intractable TLE patients. RESULTS: One had
      right temporal interictal spikes on electroencephalography (EEG) and a right
      medial temporal lobe lesion on magnetic resonance imaging (MRI). FDG-PET showed
      decreased uptake in the left temporal lobe. Right temporal ictal onset, with
      bilateral interictal epileptiform activity, occurred on intracranial EEG. He is
      seizure free after right temporal lobectomy and ganglioglioma resection. The
      second had right temporal lobe interictal and ictal EEG activity. MRI
      demonstrated right anteriomedial temporal increased T2 signal. Neuropsychology
      revealed bilateral cognitive dysfunction. FDG-PET showed left anterior temporal
      and lateral frontal hypometabolism. He is seizure free after right temporal
      lobectomy. CONCLUSION: These findings suggest that regional uptake asymmetry on
      FDG-PET may be give misleading lateralising information in TLE.

PMID- 8741123
TI  - Gabapentin in refractory partial epilepsy--a trial in India.
AB  - Gabapentin (GBP) has been shown to be effective an add-on drug for the treatment
      of refractory partial epilepsy. We undertook an open clinical trial to test its
      efficacy for the first time in India. Twenty-six patients with refractory partial
      seizures (> 4 per month) were given GBP in a titrated dose and the seizure
      frequency was noted for 3 months. The mean reduction in seizures was significant:
      15.87 (SD = 4.5) vs 5.80 (SD = 10.25). The mean percentage change (PCH) from the
      baseline was -36. Twenty-one of 26 (80%) patients had a reduction in the number
      of seizures, and 13/26 (50%) were identified as responders (> 50% reduction in
      seizures). The responders were significantly younger than the nonresponders.
      Adverse events were mild and noted in 46% patients. Although the trial has its
      limitations, this is probably the first trial of GBP in a developing country.

PMID- 8741124
TI  - Effectiveness and tolerance of clobazam in temporal lobe epilepsy.
AB  - INTRODUCTION: The main objective of this retrospective study was the further
      exploration of the loss of efficiency of the clobazam therapy (CLOB tolerance) in
      resistant temporal lobe epilepsy (TLE). MATERIAL AND METHODS: For up to 42 months
      we closely followed the state of 55 TLE patients placed on CLOB as an add-on
      therapy. Also, we sought for a connection between CLOB tolerance and clinical
      characteristics. RESULTS: By the end of the 1st month 71% of the patients were
      seizure-free; 20% improved; 3% relapsed totally and 6% did not respond at all.
      After 24 months 15% were seizure-free, 11% maintained the original improved
      state, 36% relapsed totally and 32% partially--which remained unchanged
      thereafter. Long-term efficiency was in inverse proportion to the pretreatment
      interictal spike activity. No significant cross-tolerance was noted between CLOB
      and clonazepam. CONCLUSION: Although the problem of CLOB tolerance is hardly
      overestimated, the use of CLOB in the treatment of TLE deserves consideration-
      despite the possibilities new drugs offer.

PMID- 8741125
TI  - Pharmacokinetics of dextromethorphan and dextrorphan in epileptic patients.
AB  - The present report describes the pharmacokinetic characteristics of
      dextromethorphan (DM) and its main active metabolite dextrorphan (DX) in a group
      of epileptic patients receiving comedication. Patients were sequentially dosed
      with DM 40 mg/6 h (8 weeks) and 50 mg/6 h (8 weeks) while concurrent
      antiepileptic drugs were kept stable. During baseline period, patients were
      phenotyped with regard to their drug metabolizing capacity. At the end of each
      treatment period, timed plasma DM and DX levels were determined post-dose by
      HPLC. Urine and cerebrospinal fluid f1p4) samples were also collected. The
      pharmacokinetic parameters of DM showed a wide intersubject variation. The
      genetic polymorphism of DM metabolism was identified as the possible cause of the
      observed variability. For both DM and DX mean values for Cmax and AUC increased
      in a linear fashion with dose, while the mean values of tmax and t 1/2 were not
      dependent on dose. The mean values of CL/F and Vss/F for DM were also dose
      dependent. 3-Methoxymorphinan, an N-demethylated metabolite of DM was detected in
      plasma and CSF of some patients and warrants further investigation as to its
      possible CNS effects. In conclusion, DM given in doses up to 50 mg/6 h can
      produce plasma and brain concentrations similar to the in vitro antiepileptic
      levels, without causing significant adverse effects.

PMID- 8741126
TI  - Different antiganglioside antibody pattern between relapsing-remitting and
      progressive multiple sclerosis.
AB  - INTRODUCTION: Multiple sclerosis (MS) is an autoimmune disorder, but an unique
      antigen has not been found. Antiganglioside antibodies (AGA) have been reported
      in MS, nevertheless, a clinical significance of AGA in MS has not been
      established. The aims of this study were to study AGA in sera of MS patients and
      to investigate relationships between AGA and clinical course of MS. MATERIAL AND
      METHODS: 42 patients with MS who fulfilled the criteria of clinically definite
      disease (59% RRMS, 21% SPMS, 20% PPMS), 89 patients with systemic lupus
      erythematosus and 36 healthy controls were studied. A modification of previously
      described ELISA techniques was used to estimate serum IgG and IgM anti-GM1,
      asialoGM1 and anti-GD1a antibodies. RESULTS: 47.6% of the patients showed AGA
      reactivity. Anti-GM1 was found in 38% of MS patients, anti-asialoGM1 in 23.8% and
      anti-GD1a in 33.3%. IgG was the isotype more commonly found. A correlation
      between presence of AGA and progressive disease and between anti-GD1a and PPMS
      was found. CONCLUSIONS: The presence of AGA in MS patients is elevated. In
      contrast with the results of others authors, a strong correlation between AGA and
      progressive disease is showed in our study.

PMID- 8741127
TI  - Epidemiology of multiple sclerosis in the county of Vestfold, eastern Norway:
      incidence and prevalence calculations.
AB  - The county of Vestfold in the South-eastern part of Norway has undergone two
      incidence and prevalence surveys on multiple sclerosis. The prevalence of
      definite/probable MS on January 1, 1963 was 61.6/100,000. Based on the same
      diagnostic criteria, the present study reports a slight increase in prevalence to
      86.4/100,000 on January 1st 1983. The average annual incidence was calculated for
      5 years periods from 1953 to 1983. The time periods 1953-1962 and 1973-1977
      showed age-adjusted incidence rates between 4.50 and 5.49/100,000 while the 10
      year period 1963-1972 showed significantly lower rates. The fluctuating pattern
      of MS incidence and prevalence over time supports the view that MS is not a
      stable disease, and that exogenous factors are influencing the disease pattern.

PMID- 8741128
TI  - Reflection on the geographic distribution of multiple sclerosis in France.
AB  - The geographic distribution of multiple sclerosis within the 95 Departements and
      the 21 Regions of France was defined from a 1986 nationwide prevalence series
      derived from questionnaires. This indicated a significant clustering of high
      frequency regions in the northeastern part of the country with most significantly
      low areas in the south and west. Distributions were similar to those for MS death
      rates by Departement and Region for 1968-1977, indicating geographic stability
      over time; but there was also evidence of diffusion over time. The 1986
      prevalence distribution was also compared with all published prevalence rates for
      communities of France. From all these resources we conclude that all of France
      falls within the "high frequency zone" for MS, that the nationwide prevalence
      rate is at least 50 per 100,000 population, and that there is evidence of
      geographic clustering of the disease with temporal spread of the cluster.

PMID- 8741129
TI  - Vascular cell adhesion molecule--a new approach to detect endothelial cell
      activation in MS and encephalitis in vivo.
AB  - INTRODUCTION: Leukocyte migration into inflammatory lesions is controlled by
      adhesion molecules on activated vascular endothelium. Pivotal among these are E
      selectin and the vascular cell adhesion molecule-1 (VCAM-1), which are found on
      very few cell types other than activated endothelium. METHODS: We determined the
      presence of the soluble form of these adhesion molecules (sE-selectin and sVCAM
      1) in serum and CSF of patients with multiple sclerosis (MS), viral encephalitis,
      and controls, using enzyme-linked immunosorbent assays. RESULTS: MS patients with
      active, Gadolinium-DTPA-enhancing lesions on magnetic resonance imaging had
      significantly higher sVCAM-1 serum levels than normal controls. Patients with
      viral encephalitis had significantly higher levels of sVCAM-1 in serum and
      cerebrospinal fluid than controls. sE-selectin levels showed no significant
      variations. CONCLUSION: Activated vascular endothelium controlling leukocyte
      migration may be demonstrated in MS patients in vivo by determining sVCAM-1 in
      serum. Furthermore, sVCAM-1 may be useful for monitoring inflammatory activity in
      central nervous system inflammatory disease.

PMID- 8741130
TI  - Cerebrospinal fluid nitrate levels in patients with Parkinson's disease.
AB  - It has been suggested that nitric oxide could be implicated in the neuronal
      degeneration of substantia nigra compacta in patients with Parkinson's disease.
      Recently, it has been reported decreased CSF nitrate levels (oxidation product
      that provides an indirect estimation of nitric oxide) in Parkinson's disease
      patients, assessed with a colorimetric method. We studied the CSF and plasma
      levels of nitrate with a kinetic cadmium-reduction method in 31 Parkinson's
      disease patients and 38 matched controls. The CSF and plasma nitrate levels were
      not correlated either in patient or in the control group, and they did not differ
      significantly between the two study groups. They were not influenced
      significantly by antiparkinsonian drugs in patients, although there was a trend
      for CSF nitrate levels to be higher in patients treated with levodopa or with
      dopamine agonists. CSF and plasma nitrate levels did not correlate with age at
      onset, duration, scores of the unified Parkinson's disease rating scales and
      Hoehn & Yahr staging in the patients group. These date suggest that CSF and
      plasma levels of nitrate are apparently unrelated with the risk for PD.

PMID- 8741131
TI  - Sympathetic skin response in Parkinson's disease.
AB  - Sudomotor function in 83 patients with Parkinson's disease (PD) was evaluated
      using the sympathetic skin response (SSR) and sweat response to intradermal
      acetylcholine (ACh) injection. The incidence of abnormal SSRs (36.1%) increased,
      and the size of the response decrease with the severity of the illness. Neither
      the incidence of abnormal SSRs nor the amplitudes of the responses were
      influenced by levodopa or an anticholinergic agent. The SSR therefore can be used
      to evaluate the sudomotor efferent pathway in PD patients. In all the patients
      who had no SSR response, the local sweat response to ACh showed a reduced number
      of excitable sweat glands and low sweat volume. One patient, whose local sweat
      response to ACh was markedly impaired, had unmyelinated and acetylcholinesterase
      positive fiber densities that were in the normal range in his biopsied sural
      nerve. The abnormal sweat response to ACh is considered to reflect the
      dysfunction of postganglionic sympathetic fibers in PD patients.

PMID- 8741132
TI  - Apolipoprotein E in patients with dementia of the Alzheimer type and vascular
      dementia.
AB  - The phenotypes of apolipoprotein E (ApoE) in the plasma of patients with dementia
      of the Alzheimer type (DAT) and vascular dementia (VD) were determined by the
      isoelectric focusing method. The ApoE mRNA level in the skin fibroblasts was also
      determined by the Northern blot analysis. As compared with the control subjects,
      the frequency of the ApoE epsilon 4 allele was significantly higher in the DAT
      group as well as the VD group, but was not significantly different in the
      cerebrovascular disease without dementia (CVD) group. The skin fibroblast ApoE
      mRNA level in the DAT group and the VD group was significantly lower than that in
      the control group. These findings suggest that the phenotype of ApoE is
      associated with DAT and VD, and that the lower level of ApoE mRNA may play an
      important role in the development of DAT as well as VD.

PMID- 8741133
TI  - Lack of point mutation of the APP gene in sporadic Alzheimer's disease in
      Japanese.
AB  - We investigated point mutations of the APP gene in 66 patients with sporadic
      Alzheimer's disease (AD) and 180 normal individuals by use of the PCR (polymerase
      chain reaction) method. Both the AD patients and the normal individuals were
      Japanese. We extracted DNA from blood samples using the phenol-chloroform method
      and amplified exons 16 and 17 of the APP gene by PCR. PCR products were digested
      by MBO-II (exon 16) and BCL-1(exon 17). Electrophoresis was carried out with 3%
      agarose gel and the separated fragments were stained with ethidium bromide. In
      addition we investigated other point mutations of exons 16 and 17 by use of the
      PCR-SSCP (single stranded conformation polymorphisms) method, and found no
      fragments that exhibited point mutations in the AD patients and normal
      individuals. These findings indicate that the presence of point mutation of the
      APP gene is not a major cause of AD in the Japanese population.

PMID- 8741135
TI  - Acute herpes simplex encephalitis: clinical assessment and prognostic data.
AB  - Acute herpes simplex encephalitis (HSE) has a grave outcome, and detection of
      prognostic features is of clinical importance. Thirty patients with HSE were
      assessed in a retrospective study. Diagnosis was confirmed by serological methods
      using the indirect immunofluorescence technique (IFT). Antiviral treatment was
      given to 23 of the patients. Focal convulsions were more frequent in patients
      below 18 years of age, while confusion and memory disturbances were prevalent
      among patients above 18. The final outcome was influenced by the degree of
      severity of the disease at the peak and the state of consciousness and duration
      of disease prior to the initiation of anti-viral treatment. No correlation was
      found between antibody levels in serum or in CSF and the outcome. We conclude
      that the clinical degree of severity the duration of illness prior to treatment
      and state of consciousness at the initiation of anti-viral treatment are of
      prognostic importance.

PMID- 8741134
TI  - The influence of white matter lesions on neuropsychological functioning in
      demented and non-demented 85-year-olds.
AB  - White matter lesions on computed tomography of the head were studied in relation
      to neuropsychological functioning in subjects from a representative sample of non
      demented (n = 134) and demented (n = 98) 85-year-olds. Non-demented subjects with
      white matter lesions (n = 46) scored significantly lower in tests of verbal
      ability (Synonyms), spatial ability (Block Design, Clock Test), perceptual speed
      (Identical forms), secondary memory (Thurstone Picture Memory), basic arithmetic
      (Coin Test) and the global cognitive screening test Mini-Mental State Examination
      than non-demented subjects without white matter lesions (n = 88). Demented
      subjects with white matter lesions (n = 67) scored significantly lower in tests
      of spatial ability (Block Design and Clock Test) and secondary memory (free
      recall in the MIR memory test, Ten-word memory test I and II) and in the Mini
      Mental State Examination than demented subjects without white matter lesions (n =
      31). It is concluded that white matter lesions contribute to cognitive decline in
      both non-demented and demented elderly subjects.

PMID- 8741136
TI  - Acute encephalitis.
AB  - Acute encephalitis: etiology, clinical findings and prognosis. We studied 44
      patients with acute encephalitis diagnosed in a neurological university clinic
      during an 11-year period. An etiology was found in 11 cases (25%). In 3 the cause
      was herpes simplex virus; in 2 morbilli. There were single patients in which the
      cause was mycoplasma pneumoniae, epidemic parotitis, ornithosis, infectious
      mononucleosis, influenza B-virus and recent tetanus immunization. No specific
      etiology was found in 33 (75%). Besides fever the most frequent sign was
      impairment of consciousness in 39% of cases. Four patients (9%) died. Among the
      survivors mental and/or focal neurological deficits persisted in 22 (55%). Most
      frequent was dementia in 6 cases (15% of survivors). Impaired consciousness in
      the acute phase indicated a worse prognosis (p < 0.005).

PMID- 8741137
TI  - Differential effect of NMDA and AMPA receptor blockade on protein synthesis in
      the rat infarct borderzone.
AB  - We investigated whether the known neuroprotective effects of two selective
      glutamate receptor antagonists, the NMDA antagonist MK-801 and the AMPA
      antagonist NBQX, are reflected in the regional cerebral protein synthesis rates
      (CPSR) in rats with middle cerebral artery occlusion (MCAO). Rats treated with
      either saline, MK-801 (5 mg/kg i.p.) or NBQX (30 mg/kg i.p. x 3) were subjected
      to permanent MCAO. Regional CPSR and volumes of gray matter structures displaying
      normal CPSR were measured in coronal cryosections of the brain by quantitative
      autoradiography following an i.v. bolus injection of 35S-labelled L-methionine 2
      h after occlusion. MCAO completely inhibited protein synthesis in the lateral
      part of striatum and part of the adjacent frontoparietal cortex corresponding to
      the ischemic focus. Surrounding this, a metabolic penumbra with approximately 50%
      reductions in CPSR was present. Treatment with MK-801 significantly increased the
      volume of tissue with normal CPSR in the ischemic hemisphere compared to
      controls, whereas this was not seen with NBQX treatment. The results suggest that
      MK-801 and NBQX have different effects on peri-infarct protein synthesis after
      MCAO. Since both compounds reduce infarct size, it is questionable that acute
      inhibition of protein synthesis in focal ischemia is of significant importance to
      the final outcome of a stroke lesion.

PMID- 8741138
TI  - Asymmetry of silent period evoked by transcranial magnetic stimulation in stroke
      patients.

PMID- 8741139
TI  - Guillain-Barre syndrome in South-West Stockholm, 1973-1991, 3.
      Clinicoepidemiological subgroups.
AB  - Using hierarchical cluster analysis, applied to 47 cases of Guillain-Barre
      Syndrome (GBS) incident in South-West Stockholm (SWS) during the period from
      January 1973 to June 1992, we identified three major clinicoepidemiological
      subgroups. The first subgroup, 25.5% of the cases (26.7 +/- 6.7 years), recorded
      a peak incidence at ages 20-29 years and presented significant differences from
      other subgroups, a high proportion of cases with onset at low age preceded by
      respiratory infection (83.3%) and with normal motor conduction velocity (50.0%).
      Also found, were less affected biological parameters, a rapidly progressive
      course and independence in gait at one month after onset. A second subgroup,
      27.7% of cases, was severely affected, clinically and functionally. It consisted
      predominantly of young individuals (22.7 +/- 11.1 years), with a high incidence
      (69.2% of cases) in autumn. A third subgroup, comprising 40.4% of cases, was
      older (61.1 +/- 11.0 years) and, in general, also severely affected. The
      incidence of this form appeared to be invariant with time.

PMID- 8741140
TI  - Prevalence of cervical spondylotic radiculopathy: a door-to-door survey in a
      Sicilian municipality.
AB  - INTRODUCTION: Because of the limited information on cervical spondylotic
      radiculopathy, we conducted a door-to-door two-phase survey in a Sicilian
      municipality. MATERIAL AND METHODS: We first screened for cervical spondylotic
      radiculopathy among the inhabitants of the municipality: (N = 7653, as of the
      prevalence day, November 1, 1987). Study neurologists then investigated those
      subjects suspected to have had a cervical spondylotic radiculopathy. Diagnoses
      were bases on specified criteria. RESULTS: We found 27 subjects affected by CSR
      (17 definite, 10 possible). Prevalence (cases per 1000 population) was 3.5 in the
      total population; it increased to a peak at age 50-59 years, and decreased
      thereafter. The age-specific prevalence was consistently higher in women.
      CONCLUSIONS: Comparison with other prevalence studies shows similar age-specific
      patterns, but different magnitudes, which may partly reflect methodologic
      differences across studies.

PMID- 8741141
TI  - Familial facioscapulohumeral muscular dystrophy: phenotypic diversity and genetic
      abnormality.
AB  - We report two cases showing facioscapulohumeral muscular dystrophy (FSHD) with
      phenotypic diversity but the same genetic abnormality detected by a p13E-11
      probe. The proband, a 26-year-old woman, showed an early onset, tortuosity of
      retinal arterioles and respiratory failure. The 53-year-old mother of the proband
      had limb-girdle (L-G) type muscular weakness with very mild facial involvement.
      Muscle biopsy showed perivascular cell infiltration in both patients. These cases
      suggest that the phenotypic diversity ranges from L-G type weakness to severe
      respiratory failure in FSHD family.

PMID- 8741142
TI  - Diagnostic value of in situ muscle fiber conduction velocity measurements in
      myopathies.
AB  - In situ studies on muscle fiber conduction velocity (MFCV) were performed in 54
      patients with histologically and biochemically defined myopathies. MFCV was
      measured over a 10 cm segment of the rectus femoris muscle by intramuscular
      stimulation and recording. Muscle disorders included muscular dystrophies,
      myotonic dystrophy, inflammatory myopathies, metabolic myopathies, endocrine
      myopathies, and congenital myopathies with structural abnormalities. Ten healthy
      volunteers served as controls. MFCV was significantly reduced in all patients
      except those with a defect in glycolysis and those that had recovered from acute
      myositis. MFCV did not vary with either sex. age or the duration of the disease.
      This shows that MFCV slowing is an unspecific finding in most myopathies.
      However, in some patients with normal needle electromyography, MFCV provided
      additional information in diagnosing muscle disease.

PMID- 8741143
TI  - Random mitotic segregation of mitochondrial DNA in MELAS syndrome.
AB  - We describe the heterogeneity of clinical features and molecular genetic
      characteristics of the probands and other members in two families with
      mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes
      (MELAS) syndrome. A point mutation at the 3243rd nucleotide position of mtDNA was
      found only in some of the maternal lineage members of the two families.
      Furthermore, the proportions of mutant mtDNA were varied and found only in some
      tissues of the individuals. Intriguingly, in some subjects, the mutant mtDNA was
      found in blood cells or hair follicles but was absent in muscles. The data do not
      support the notion of a selective advantage of wild-type mtDNA to rapidly
      replicating cells. We suggest that a rapid replicative segregation may occur in
      early embryogenesis.

PMID- 8741144
TI  - Mycoplasma pneumoniae infection associated with an acute brainstem syndrome.
AB  - A patient who developed an acute brainstem syndrome following Mycoplasma
      pneumoniae respiratory infection is reported. MRI showed changes consistent with
      brainstem demyelination. Clinical features and laboratory investigations support
      an immune mediated mechanism with no evidence of direction CNS invasion. On the
      basis of this case and a review of the literature, we postulate two mechanisms
      for the development of M. pneumoniae associated CNS disease: direct CNS invasion
      causing meningitis and an immune-mediated acute disseminated encephalomyelitis
      (ADEM). This has obvious therapeutic implications.

PMID- 8741145
TI  - Routine early CT-scan is cost saving after minor head injury.
AB  - Significant hospital resources are invested in early detection of intracranial
      complications after minor head injuries (MHI). This study focuses on economic
      aspects of MHI management. 88 MHI patients underwent routine early CT-scan and at
      least 24 h in-hospital observation. The cost of this management was calculated,
      and compared to estimated costs of three alternative management protocols. CT
      scans demonstrated intracranial lesions in eight (9%) patients, but none required
      neurosurgical intervention. The expense of our management was Norwegian Kroner
      (NOK) 576,136. An alternative management protocol including routing early CT-scan
      and discharge of patients with normal CT-findings, Glasgow coma score > or = 14
      and no neurological deficits, was found to be safe, and estimated to reduce costs
      with 43% to NOK 326,669. It is concluded that routine early CT-scan is the most
      reliable and cost saving management procedure after MHI.

PMID- 8741146
TI  - Effects of ethanol administration on brain neurotensin-like immunoreactivity in
      rats.
AB  - The effects of acute and chronic ethanol administration on neurotensin-like
      immunoreactivity (NTLI) were investigated in discrete regions of the rat brain.
      Rats were administered a single dose (5 g/kg) of ethanol or rendered ethanol
      dependent by repeated forced drinking of a 20% ethanol solution (6-15 g/kg) for 4
      days and tested while still intoxicated or at 12-19 h (W-1) or 7 days (W-2) after
      ethanol withdrawal. Increases in NTLI were seen in the caudate-putamen in the
      toxic, W-1 and W-2 groups and decreases were observed in the midbrain in the
      toxic and W-1 groups. It was assumed that ethanol produced the changes of NTLI in
      the caudate-putamen and midbrain through its actions upon the dopaminergic
      system.

PMID- 8741147
TI  - Wilson's disease: resolution of MRI lesions following long-term oral zinc
      therapy.
AB  - A 28-year-old man with Wilson's disease developed neurological deterioration
      after a low-dose of d-penicillamine treatment for 2 weeks. He showed an akinetic
      rigid syndrome with generalized dystonia. Brain magnetic resonance images (MRI)
      on T2 and proton weighted images showed an increased signal intensity over the
      thalamus, basal ganglia and brainstem, especially the midbrain and pons. After
      treatment had been changed to zinc sulphate, the akinetic-rigid syndrome and
      dystonia were improved slowly in the following 4 years. Serial MRI studies showed
      a gradual resolution of the lesions. His current neurological status was almost
      normal except for dysarthria and mild intention tremor.

PMID- 8741148
TI  - Unilateral spatial neglect in Alzheimer's disease. A line bisection study.
AB  - Neuropsychological studies on Alzheimer's disease (AD) have rarely mentioned
      about unilateral spatial neglect in spite of widespread use of visuospatial
      tasks. We reported a 62-year-old woman with probable AD who showed moderate
      dementia with left unilateral spatial neglect and relatively preserved language
      function. An extensive line bisection study with either hand confirmed her having
      left unilateral spatial neglect. Single photon emission computed tomography
      revealed relative hypoperfusion in the right temporal and parietal regions. AD
      patients with disproportionate right hemisphere dysfunction may exhibit left
      unilateral spatial neglect if tested adequately in the stage of mild to moderate
      dementia. We consider that application of the line bisection test to AD patients
      contributes to estimation of their right hemisphere function.

PMID- 8741149
TI  - Management of retinal redetachment following silicone-oil removal.
AB  - The aim of the present investigation was to study the clinical course of eyes
      presenting with retinal redetachment after silicone-oil removal (SOR), with
      special regard being paid to the long-term visual outcome. Between October 1989
      and September 1994, SOR was performed on a consecutive series of 262 eyes that
      had previously undergone vitrectomy combined with silicone-oil injection for
      complex retinal detachments. The records of these patients were analyzed
      retrospectively. The mean follow-up period after redetachment following SOR was
      26.3 (range 6-45) months. Redetachment occurred in 35 eyes (13.4%), mostly within
      1-3 months of SOR. Redetachment was not dependent on the surgical procedure or
      the underlying disease. A total of 24 eyes were revitrectomized and a stable flat
      retina was the result in 23 eyes (65.7%). At the latest follow-up visit, 18 eyes
      (51.4%) had a visual acuity (VA) of > or = 0.02 and 14 eyes (40%) had a VA of >
      or = 0.1. In 12 eyes (34.3%) the final VA equalled the best VA recorded before
      redetachment; an increase in VA occurred in 6 eyes (17.1%) and a deterioration
      was noted in 17 eyes (48.6%). Only 6 of the 17 eyes that deteriorated had
      displayed a VA of > or = 0.02 prior to SOR and lost formed vision due to
      redetachment; these 6 eyes represent 17.1% of the eyes presenting with
      redetachment after SOR and 2.3% of all 262 eyes that had undergone SOR. These
      observations demonstrate that revitrectomy is an effective treatment for retinal
      redetachment after silicone-oil removal. The final failure rate does not appear
      high enough to justify a contraindication for routine removal of silicone oil,
      especially since it remains a matter of speculation as to whether these eyes
      would have fared better had removal of silicone oil been avoided.

PMID- 8741150
TI  - Apoptotic cell death in proliferative vitreoretinopathy.
AB  - Apoptosis is a selective event of physiological cell deletion that plays a
      crucial role in the development of numerous tissues, including the retina. In
      this paper we report the occurrence of apoptosis in epiretinal membranes derived
      from patients with proliferative vitreoretinopathy (PVR). Detection of apoptosis
      was performed by an in situ DNA-end labeling technique using terminal transferase
      mediated deoxyuridine triphosphate (dUTP) incorporation. Apoptotic nuclei
      exhibiting chromatin condensation and fragmentation were also identified by
      acridine orange fluorescence. Apoptosis was detected in varying numbers of cells.
      The typical appearance of apoptotic nuclei, including nuclear chromatin
      condensation, was detected scattered inhomogeneously throughout the epiretinal
      membranes, in clusters, or even in single cells. Induction of apoptosis in human
      retinal pigment epithelial (RPE) cells by daunomycin could be demonstrated by in
      situ DNA end labeling and by quantitative determination of cytoplasmatic histone
      associated DNA fragments using a photometric enzyme immunoassay. Since apoptosis
      has been shown to be an important factor in the growth control of various
      untransformed and neoplastic cell populations, the pharmacological induction of
      apoptosis in epiretinal membranes could result in a new approach toward
      inhibiting cellular proliferation in PVR.

PMID- 8741151
TI  - Influence of cataract surgery on the diabetic eye: a prospective study.
AB  - The course of diabetic retinopathy following phacoemulsification and in-the-bag
      implantation of an intraocular lens (IOL) was studied prospectively in 223
      patients (223 eyes). A total of 205 eyes were followed for 6 months. The
      nonoperated fellow eyes served as a control group. At the time of surgery, 158
      patients had no diabetic retinopathy, 45 showed untreated background retinopathy,
      and 20 had more serious retinopathy with previous coagulation therapy. At 6
      months of follow-up, 18.4% of the operated eyes without preoperative retinopathy
      developed background retinopathy, as did 14.3% of the untreated fellow eyes.
      Worsening of preexisting diabetic retinopathy during the observation period
      occurred in 27.6% of the operated eyes and in 29.3% of the non-operated eyes.
      Although the final visual acuity achieved in our patients was poorer than that
      reported for nondiabetics, our functional results were satisfying: 94.1% of the
      operated eyes showed improved visual acuity 6 months postoperatively, 2.4%
      deteriorated, and 3.4% were unchanged. We therefore conclude that cataract
      surgery in diabetic patients can be performed with an acceptable risk of
      complications. Furthermore, worsening of diabetic retinopathy seems to be
      correlated not with the cataract surgery but with the natural course of diabetic
      vascular disease.

PMID- 8741152
TI  - Morphological and biomorphometrical observations on laser thermal keratoplasty.
      Histological and biomorphometrical examination of the relationship between
      refractive change and the volume following Cr:Tm:Ho:YAG laser treatment.
AB  - Laser thermal keratoplasty (LTK) is currently under clinical trial for the
      correction of hyperopia and hyperopic astigmatism by means of collagen
      coagulation in the peripheral cornea. The purpose of our study was to optimize
      the ratio between the volume of damaged corneal stroma and the refractive effect
      so as to minimize potential side effects such as endothelial damage or induction
      of glare phenomena. We therefore performed histological and morphometrical
      examinations of enucleated pig eyes to determine the relationship between the
      coagulated stromal volume and the refractive change after LTK using a pulsed
      Cr:Tm:Ho:YAG laser (wavelength 2.12 microns) on enucleated pig eyes. The
      refractive change was documented with a Littman ophthalmometer. Morphometrical
      analysis was performed using polarized light microscopy of sirius red-stained
      specimens. This special stain separated the thermally changed stroma into a dark
      nonbirefringent center and a birefringent peripheral zone. The volume of both
      zones was positively correlated with the refractive change induced. The volume
      was in turn influenced by the choice of laser parameters. From the ratio of the
      volume to the refractive change it was found that pulse energies above 30 mJ let
      to an enlargement of the coagulation volume without increasing the refractive
      change effectively. The use of high pulse energies did not improve the effect of
      LTK but only increased the risk of unwanted side effects. However, an increase in
      the laser repetition rate at a constant pulse number per spot led to refractive
      changes with minimal coagulation volume. The highest relative refractive change
      was achieved with a dark central zone and a birefringent zone, each having a
      volume of about 50-80 x 10(-3) mm3.

PMID- 8741153
TI  - Therapy of Behcet's disease.
AB  - Behcet's disease (BD) is a multisystem vasculitis of unknown origin. In this
      retrospective study we analyzed the therapy of 32 patients seen between 1978 and
      1993 at the Departments of Rheumatology, Ophthalmology, and Dermatology of the
      Tubingen University Clinic. The aim of this study was to evaluate the efficacy of
      different therapeutic strategies concerning different organ manifestations of the
      disease, especially eye disease. A total of 20 patients had cutaneous
      manifestations or arthritis. Whereas treatment with colchicine (Col),
      azathioprine (AZA), cyclosporine (CSA), or steroids (Ster) produced only partial
      remissions, a combination of CSA, AZA, and steroids led to complete remissions.
      Interferon-gamma (IFN-gamma) therapy led to remission rates of 60% (complete) and
      20% (partial). In all, 22 patients had uveitis (posterior or panuveitis).
      Steroids were effective in only 50% of the patients and Col was partially
      effective in 66%. AZA induced a remission in 71% of cases and CSA was partial
      effective in 60%. The threshold combination of AZA, CSA, and Ster induced a
      complete remission in 66% of the patients. IFN-gamma was ineffective in 80%. IFN
      alpha was used in one patient only and induced a complete remission. These
      results demonstrate that although our patient group is too small to allow
      significant conclusions to be drawn, in terms of the literature, for
      mucocutaneous disease and arthritis, IFNs might be the best therapy, whereas for
      uveitis as well as other more severe features of the disease, CSA or AZA + Ster
      should be used. If the latter are ineffective, the threefold combination (AZA,
      CSA, Ster) is probably the most effective alternative. The significance of IFN
      alpha will be evaluated in further studies.

PMID- 8741154
TI  - Sympathetic ophthalmia: an immunohistochemistry study of four cases.
AB  - We present histological and immunohistochemical data on four cases of sympathetic
      ophthalmia, a disease that is believed to occur predominantly after perforating
      injury to the eye. Only a few cases without previous perforation have been
      reported. Nevertheless, sympathetic ophthalmia should be taken into consideration
      if there is a bilateral intraocular inflammation, even without trauma, as in two
      of our cases (cases 1 and 2). An unusual case after uneventful intracapsular
      cataract extraction and a posttraumatic "classic" case are also presented (cases
      3 and 4). We found a granulomatous infiltration of the uveal tract by
      lymphocytes, plasma cells, and epithelioid cells, particularly of the choroid.
      Dalen-Fuchs nodules were found in all cases, the second case also being
      associated with phacoanaphylaxis. Case 1 and 4 showed immunohistochemically a
      predominance of CD3-positive cells (T-lymphocytes), whereas in cases 2 and 3,
      many cells surprisingly stained positively for L26 (B-lymphocytes). In case 2 the
      immune response may have been altered by the additional phacoanaphylaxis. In all
      four cases, scattered epithelioid cells stained positively for CD 68. We conclude
      that in cases of bilateral uveitis, even without previous penetrating injury or
      after common intraocular surgery, sympathetic ophthalmia as a possible cause
      should be taken into consideration because an early diagnosis with subsequent
      enucleation of the exciting eye is of decisive influence on the course of the
      disease.

PMID- 8741155
TI  - Restricted applicability of the polymerase chain reaction for the diagnosis of
      ocular toxoplasmosis.
AB  - The laboratory confirmation of ocular toxoplasmosis has been reported to be
      facilitated by the polymerase chain reaction (PCR) technique in anterior chamber
      taps. We utilized PCR specific for a sequence of the Toxoplasma gondii B 1 gene
      with a length of 194 bp. The sensitivity was adjusted to ten genomic copies per
      sample in stained gel and two copies after DNA hybridization using a digoxygenin
      labeled probe. We amplified DNA from 43 aqueous, 14 serum, and 32 white blood
      cell (WBC) samples obtained from 31 consecutive otherwise healthy patients with
      the clinical diagnosis of ocular toxoplasmosis. In the series investigated, 1/43
      aqueous samples and 2/32 WBC samples were found to contain detectable amounts of
      target DNA. An inhibition of the PCR by the aqueous humor as a reason for the low
      detection rates was excluded. Thus, we conclude that either the sensitivity of
      aqueous humor PCR is not sufficient for use in the routine diagnosis of ocular
      toxoplasmosis in immuno-competent individuals or the anterior chamber is not the
      proper compartment for investigation of this protozoal disease using this
      approach.

PMID- 8741156
TI  - Cerebral activity during visual stimulation: a positron emission tomography and
      functional magnetic resonance imaging study.
AB  - Stimulation of cerebral areas induces a regional increase in blood flow and
      metabolism. Positron emission tomography (PET) is an established procedure to
      localize cerebral regions of enhanced activity. Exposure to a radioactive
      indicator and limited spatial and temporal resolution are disadvantages of this
      method as compared with other imaging techniques, but anatomical orientation can
      be improved by matching PET images with high-resolution magnetic resonance
      imaging (MRI) scans. Recently, functional MRI (fMRI) has arisen as an alternative
      method. This procedure presumably detects changes in the paramagnetic properties
      of hemoglobin, depending on its oxygenation state, as well as an increased
      regional blood flow in activated cerebral areas. These structures can be
      visualized using sensitive scanning techniques and appear with bright signal
      intensities. Visual stimulation was performed with the help of a high-resolution
      color VDU for PET registration and of an LCD video projector for fMRI (1.5 T).
      Hemifield stimulation as well as subtraction between images of flickering and
      stable random dot stimuli showed a preferential activation of the primary visual
      cortex. In addition, the first MRI results obtained during stimulation with
      moving gratings are demonstrated; hereby, preferentially extrastriate regions
      presumably responsible for motion detection were activated.

PMID- 8741157
TI  - A ray tracer for ophthalmological applications.
AB  - Ray tracing with a personal computer allows realistic simulation of optical
      properties of the human eye. Patterns of point sources are used as objects. The
      path of light rays is calculated between the point source and the retina for a
      Gullstrand eye model with improved parameters; the normal eye model has a
      resolution limit close to the natural resolution limit of the human eye. The
      image formed on the retina is projected back to a screen at the distance of the
      object so as to simulate image interpretation by the brain. Refractive errors are
      modeled by a change in eye parameters and corrected by eyeglasses or/and contact
      lenses or by an artificial intraocular lens. For optic correction the parameters
      of seeing aids can be fitted automatically by a least-squares routine. The effect
      of faulty eye correction on image quality is visualized by using a photograph of
      a realistic scene as an object.

PMID- 8741158
TI  - Effects of amphetamine at the beginning of the light cycle on multiple indices of
      motor activity in the rat.
AB  - The motor effects of a single dose of d-amphetamine on internally synchronized
      male Sprague Dawley rats and its dose response relationship at the beginning of
      the light cycle was investigated using a computerized monitoring system. After 7
      days of acclimatization to light/dark cycle and 2 days of baseline monitoring,
      rats were randomized to a no-treatment time control group (n = 12) or to receive
      0 (vehicle), 0.6, 1.25, 2.5, or 10 mg/kg d-amphetamine (n = 8 each) 1 h into the
      light cycle of day 3, and monitored for an additional post-treatment day 4. In
      the time control group, there was a stable baseline level of activity for both
      light and dark phases. All doses (0.6, 1.25, 2.5, and 10 mg/kg) significantly
      elevated (P < 0.01) locomotor activity compared to baseline, but not all activity
      parameters (horizontal activity, total distance, vertical activity, stereotypic
      activity, and number of stereotypic movements) followed the same pattern of
      response. The maximum increase in all parameters, except vertical activity,
      occurred at 1.25 mg/kg (P < 0.001). The duration of drug effect increased with
      dose, with increased activity lasting until the fifth hour after injection of 10
      mg/kg. ANOVA revealed no consistent long term effects, with all parameters
      returning to baseline levels on the day after treatment. The range of variables
      and the establishment of baseline values at the time of injection for each rat
      provides the potential to characterize circadian patterns of locomotor activity
      and chronopharmacologic effects of drugs on motor activity, including
      sensitization and tolerance.

PMID- 8741159
TI  - Effects of combined block of alpha 1-adrenoceptors and NMDA receptors on spatial
      and passive avoidance behavior in rats.
AB  - The present study was designed to investigate the interactions between alpha 1
      adrenoceptors and NMDA receptors in modulating spatial navigation and passive
      avoidance behavior in rats. Pretraining treatment with prazosin, and alpha 1
      adrenoceptor antagonist, at 2 mg/kg i.p., impaired acquisition performance in a
      water maze navigation test and had no effect on passive avoidance behavior.
      Posttraining and pretest injections of prazosin had no effect on water maze or
      passive avoidance behavior. Pretraining treatment with ((+/-))-3-(2
      carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), a competitive NMDA
      receptor antagonist, does dependently (3 and 10 mg/kg) impaired passive avoidance
      and water maze behavior. Posttraining treatment with CPP had no effect on water
      maze and passive avoidance behavior. A pretraining combination of subthreshold
      doses of CPP (1 mg/kg) and prazosin (1 mg/kg) impaired water maze behavior. A
      combination of subthreshold doses of CPP (3 mg/kg) and prazosin (1 mg/kg)
      injected posttraining or pretest had no marked effect on water maze or passive
      avoidance performance. A control experiment showed that CPP 3 mg/kg or CPP 1
      mg/kg and prazosin 1 mg/kg injected pretraining had no effect on cue navigation
      to a clearly visible platform, but CPP 10 mg/kg markedly impaired performance.
      The present results indicate that alpha 1-adrenoceptors and NMDA receptors may
      synergistically regulate acquisition of spatial navigation performance.
      Therefore, it would be interesting to study the effects of combined stimulation
      of alpha 1-adrenoceptors and NMDA receptors on age-related memory defects.

PMID- 8741160
TI  - Role of delta-opioid receptors in mediating the aversive stimulus effects of
      morphine withdrawal in the rat.
AB  - An unbiased place preference conditioning procedure was used to examine the role
      of delta-opioid receptors in mediating the aversive effects of opioid withdrawal.
      Rats were implanted s.c. with two pellets each containing placebo or 75 mg
      morphine. Single-trial conditioning sessions with saline and the opioid receptor
      antagonists naloxone (0.001-1.0 mg/kg, s.c.), naltrindole (0.01-3.0 mg/kg, s.c.)
      or naltriben (0.01-3.0 mg/kg, s.c.) commenced 4 days later. During these
      conditioning sessions, physical signs of withdrawal were also quantified. Tests
      of conditioning were conducted on day 5. Naloxone in doses of 0.01-1.0 mg/kg
      produced significant conditioned place aversions in morphine-implanted animals. A
      dose of 0.01 mg/kg produced few physical withdrawal signs whereas higher doses
      resulted in marked wet dog shakes, body weight loss ptosis and diarrhea. No such
      effects were observed in control (placebo-implanted) animals. Administration of
      the selective delta-opioid receptor antagonists naltrindole and naltriben
      produced dose-related place aversions in morphine-implanted animals. The
      magnitude of these effects did not differ from that observed with naloxone. The
      minimum effective doses of naltrindole and naltriben were 0.1 mg/kg. Doses of 0.1
      1.0 mg/kg produced few, if any, somatic signs of withdrawal whereas higher doses
      of these antagonists only produced diarrhea and wet-dog shakes. Other withdrawal
      signs were absent. In contrast to the opioid receptor antagonists tested, the
      dopamine D1 receptor antagonist SCH23390 failed to produced conditioned place
      aversions or physical signs of withdrawal in morphine-pelleted animals. These
      data demonstrate that the selective blockade of either delta- or mu-opioid
      receptors is sufficient to induce conditioned aversive effects in morphine
      dependent animals. They also indicate that physical symptoms associated with
      precipitated morphine withdrawal differ depending upon the opioid receptor
      antagonist employed.

PMID- 8741161
TI  - Effect of the selective CCKB receptor antagonist LY288513 on conditioned fear
      stress in rats.
AB  - In order to investigate the involvement of cholecystokinin (CCK) in the
      regulation of anxiety, the effect of the selective non-peptide CCKB receptor
      antagonist LY288513 ((4S, 5R)-N-(4-bromophenyl)-3-oxo-4,5-diphenyl-1-1
      pyrazolidinecarboxamide+ ++) on freezing behavior induced by conditioned fear
      stress was examined using a time-sampling procedure. Rats were individually
      subjected to 5 min of inescapable electric footshock in a shock chamber. Twenty
      four hours after the footshock, the rats were again placed in the shock chamber
      and observed for 5 min without shocks: this procedure is termed conditioned fear
      stress. Subcutaneous administration of LY288513 30 min before footshock (0.3
      mg/kg) and 30 min before conditioned fear stress (0.03 mg/kg) reduced conditioned
      freezing. This indicates that LY288513 blocked both the acquisition and
      expression of conditioned fear. The relatively selective non-peptide CCKA
      receptor antagonist, lorglumide (D, L-4-(3,4-dichlorobenzoylamino)-5
      (diphentylamino)-5-oxo-pent anoic acid), blocked the expression of conditioned
      fear, though only at a high dose (1.0 mg/kg). The peripheral non-peptide CCKA/B
      receptor antagonist, loxiglumide (D, L-4-(3,4-dichlorobenzoylamino)-5- (N-3
      methoxypropyl-pentylamino)-5-oxo-pentanoic acid), failed to do so. These results
      suggest that brain CCKB receptors are involved in the regulation of anxiety.

PMID- 8741162
TI  - Cutaneous antihistaminic action of cetirizine and dose-related EEG concomitants
      of sedation in man.
AB  - The cutaneous antihistaminic action (prick test; 1:100, 1:200 and 1:1000) and
      neuropsychological and electroencephalographic (EEG) concomitants of sedation
      following the histamine H1 receptor antagonist cetirizine (10- and 20-mg acute
      oral doses) and chlorpheniramine, 4 mg, were investigated in a cross-over,
      placebo-controlled study in healthy male volunteers (age 23-29 years). With an
      average Cmax of cetirizine of 697.0 ng/ml (10 mg) and 1000.2 ng/ml (20 mg), the
      diameter of histamine-induced skin weals was reduced by 24.0-74.9% depending on
      histamine concentration and with no dose dependence for cetirizine. Placebo and
      chlorpheniramine were ineffective. Behavioral or neuropsychological signs of
      sedation were never observed. An increase of the 6.5-14.5 Hz EEG power, with
      anterior scalp preponderance, was observed after chlorpheniramine or cetirizine
      20 mg. This effect of cetirizine was accounted for by a substantial increase of
      power in the 6.5-8.0 Hz frequency subsegment and is regarded, for these
      experimental conditions, as an established early EEG indication of mild sedation
      (vigilance 'state A'). No EEG effects were observed after placebo or cetirizine
      at the 10 mg dose. The existence of some histaminergic (H1) specificity of the
      mechanisms modulating vigilance and of a threshold dose of cetirizine for
      sedative action is suggested.

PMID- 8741163
TI  - Azelastine protects against CA1 traumatic neuronal injury in the hippocampal
      slice.
AB  - Activation of NMDA receptors appears to play a important role in traumatic
      neuronal injury. Additionally, N-methyl-D-aspartate (NMDA) excitotoxicity may
      involve leukotriene production. Therefore, we investigated whether azelastine, an
      anti-allergic agent inhibiting the synthesis and release of leukotrienes, could
      protect against CA1 traumatic neuronal injury in the hippocampal slice. Fluid
      percussion trauma produced evidence of severe neuronal injury with CA1 antidromic
      population spike amplitude recovering after 95 min to only a mean 16 +/- 1 % S.E.
      of initial amplitude. With 15 microM azelastine treatment given after trauma for
      35 min this recovery improved to 112 +/- 17%. The azelastine EC50 for this
      protection was 10 microM. Significant protection was also seen with azelastine
      application begun 15 min after trauma. Azelastine also protected the ability to
      induce long-term potentiation after trauma. The specific leukotriene inhibitors,
      MK-571 and MK-886, similarly provided significant neuroprotection. These findings
      suggest that CA1 traumatic neuronal injury may be mediated by leukotriene
      production.

PMID- 8741164
TI  - Tolerance to the antinociceptive effect of epibatidine after acute and chronic
      administration in mice.
AB  - Epibatidine is a novel potent antinociceptive agent that acts through nicotinic
      receptors. In this study we investigated the development of tolerance to the
      antinociceptive effects of epibatidine enantiomers after acute and chronic
      administration in mice using the tail-flick test. Contrary to nicotine, mice
      treated with epibatidine enantiomers at different times and doses did not develop
      significant tolerance after s.c. acute nor after repeated injections. In mice
      that chronically received (+)-epibatidine, no significant tolerance was seen
      after acute challenge with (+)-epibatidine. However, a significant shift in (-)
      epibatidine's dose-response curve was obtained in animals that received (-)
      epibatidine. In nicotine-tolerant animals, no significant tolerance was seen
      after acute challenge with (+)-epibatidine. However, the animals were less
      sensitive to the acute (-)-epibatidine challenge. Our results show that
      development of tolerance to epibatidine antinociceptive effects has a different
      profile and characteristics than that found for nicotine.

PMID- 8741165
TI  - Biphasic effects of intracerebroventricular interleukin-1 beta on mechanical
      nociception in the rat.
AB  - The effects of interleukin-1 beta on the mechanical nociceptive threshold in rat
      were examined using the paw-pressure test. An intracerebroventricular (i.c.v.)
      injection of interleukin-1 beta at doses of 10 and 100 pg/rat caused hyperalgesia
      to mechanical stimuli. Higher doses of interleukin-1 beta (1 and 10 ng/rat)
      induced an analgesic effect. The coadministration of the interleukin-1 receptor
      antagonist completely antagonized the hyperalgesic and analgesic effects of
      interleukin-1 beta. An i.c.v. injection of alpha-helical-corticotropin-releasing
      factor [9-41] 15 min prior to interleukin-1 beta administration completely
      blocked the hyperalgesic and analgesic effects of interleukin-1 beta. An i.c.v.
      injection of sodium salicylate 15 min prior to interleukin-1 beta administration
      inhibited the hyperalgesic effect of interleukin-1 beta, but not the analgesic
      effect. These results suggest that interleukin-1 beta produces biphasic effects
      on the mechanical nociceptive threshold through the interleukin-1 receptor in the
      brain and that a corticotropin-releasing factor-mediated pathway is involved.
      Furthermore, the hyperalgesic effect of interleukin-1 beta may be mediated by
      prostaglandins.

PMID- 8741166
TI  - Chronic treatment with citalopram induces noradrenaline receptor hypoactivity. A
      microdialysis study.
AB  - To investigate whether chronic citalopram administration influences the cyclic
      AMP (cAMP) synthesis in vivo, microdialysis was used to assess citalopram-induced
      alterations in extracellular concentrations of cAMP in the dorsal hippocampus of
      freely moving rats. Citalopram administration for 4 weeks (40 mg/kg p.o. daily)
      did not affect the baseline levels of cAMP but decreased the noradrenaline
      induced enhancement of cAMP levels. No change in forskolin-induced enhancement of
      cAMP levels was observed. Citalopram in situ did not exert any effect on the cAMP
      levels. These data support the hypothesis that chronic administration of
      antidepressants alters the function of noradrenergic receptors.

PMID- 8741167
TI  - Frequency-dependent inhibition of neurotransmitter release by besipirdine and HP
      184.
AB  - We have described the interaction of besipirdine (HP 749, N-(n-propyl)-N-(4
      pyridinyl)-1H-indol-1-amine hydrochloride) with voltage-dependent Na+ channels
      (Tang et al., 1995, Br. J. Pharmacol. 116,2468). Here we describe studies with
      besipirdine and a related compound, HP 184 (N-(n-propyl)-3-fluoro-4-pyridinyl)-1H
      3-methylindol-1-amine hydrochloride), showing that this interaction is voltage
      dependent and leads to frequency-dependent inhibition of electrically stimulated
      neurotransmitter release. Thus, the inhibition of veratridine-induced increases
      in intracellular Ca2+ was enhanced by depolarization with KCl (IC50 shifted from
      23.8 +/- 1.4 microM in 5 mM KCl to 7.3 +/- 1.2 microM in 15 mM KCl for
      besipirdine and from 58.2 +/- 1.3 microM for HP 184). Moreover, the enhancement
      of electrically stimulated [3H]norepinephrine release by besipirdine was
      diminished at higher frequencies of stimulation. As has been previously suggested
      for such compounds, we predict that besipirdine would act as a filter in the
      brain allowing signalling at low frequencies but blocking transmission at high
      frequencies.

PMID- 8741168
TI  - Antinociceptive and antitussive effects of morphine in the DA-bg/bg (beige) rat.
AB  - Antinociceptive and antitussive effects of morphine were studied in DA-bg/bg
      (Beige) rats. Intraperitoneal administration of morphine (10 mg/kg) produced a
      marked antinociceptive effect, in the tail-flick test, in Beige rats and DA rats,
      a progenitor strain rats. There was no significant difference in the peak
      antinociceptive effect of morphine between Beige rats and DA rats. The
      antinociceptive effect of morphine in both Beige rats and DA rats was
      significantly reduced following pretreatment with a low dose (0.3 mg/kg, i.p.) of
      naloxone or naltrexonazine (1 mg/kg, s.c.), a selective mu 1-opioid receptor
      antagonist. Morphine suppressed coughs dose dependently at doses between 0.3-3
      mg/kg, i.p., in Beige rats and between 0.1-1.0 mg/kg, i.p., in DA rats. The
      antitussive potency of morphine in Beige rats was less than that in DA rats. The
      antitussive effect of morphine was significantly antagonized by pretreatment with
      naloxone (0.3 mg/kg, i.p.) in both Beige rats and DA rats. However, pretreatment
      with naltrexonazine (1 mg/kg, s.c.), a selective mu 1-opioid receptor antagonist,
      had no effect on the antitussive effect of morphine. These results suggest that
      Beige rats are hyporesponsive to the mu 2-opioid receptor-mediated antitussive
      effect, but not to the mu 1-opioid receptor-mediated antinociceptive effect.

PMID- 8741169
TI  - Presynaptic 5-HT autoreceptors modulate N-methyl-D-aspartate-evoked 5
      hydroxytryptamine release in the guinea-pig brain cortex.
AB  - Guinea-pig cerebral cortical slices preincubated with [3H]5-hydroxytryptamine
      ([3H]5-HT) were superfused with Mg(2+)-free Krebs' solution. N-Methyl-D-aspartate
      (NMDA) stimulated tritium overflow in a concentration-dependent manner. The NMDA
      evoked overflow was abolished by omission of CA2+ or presence of 1.2 mM Mg2+, but
      only partly inhibited by tetrodotoxin. The competitive and noncompetitive NMDA
      receptor antagonists, DL-(E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP
      37849) and dizocilpine, respectively, also blocked the stimulatory effect of
      NMDA. Furthermore, the NMDA-evoked tritium overflow was inhibited by 5
      carboxamidotryptamine in a manner susceptible to blockade by methiothepin, which
      given alone facilitated overflow. This facilitatory effect was increased in the
      presence of 6-nitroquipazine, a selective 5-HT reuptake inhibitor. It is
      concluded that the release of 5-HT in the guinea-pig cerebral cortex is
      stimulated via NMDA receptors, which are in part located on the serotoninergic
      axon terminals, and that the NMDA-evoked 5-HT release is modulated via inhibitory
      5-HT autoreceptors.

PMID- 8741170
TI  - The cardiovascular protective role of docosahexaenoic acid.
AB  - Dietary fish oils rich in n-3 polyunsaturated fatty acids can modulate a diverse
      range of factors contributing to cardiovascular disease. This study examined the
      relative roles of eicosapentaenoic acid (20:5 n-3; EPA) and docosahexaenoic acid
      (22:6 n-3; DHA) which are the principal n-3 polyunsaturated fatty acids regarded
      as candidates for cardioprotective actions. At low dietary intakes (0.4-1.1% of
      energy (%en)), docosahexaenoic acid but not eicosapentaenoic acid inhibited
      ischaemia-induced cardiac arrhythmias. At intakes of 3.9-10.0%en, docosahexaenoic
      acid was more effective than eicosapentaenoic acid at retarding hypertension
      development in spontaneously hypertensive rats (SHR) and inhibiting thromboxane
      like vasoconstrictor responses in aortas from SHR. In stroke-prone SHR with
      established hypertension, docosahexaenoic acid (3.9-10.0%en) retarded the
      development of salt-loading induced proteinuria but eicosapentaenoic acid alone
      was ineffective. The results demonstrate that purified n-3 polyunsaturated fatty
      acids mimic the cardiovascular actions of fish oils and imply that
      docosahexaenoic acid may be the principal active component conferring
      cardiovascular protection.

PMID- 8741171
TI  - The influence of hyperthyroidism on pharmacologically induced contractions of
      isolated resistance arteries.
AB  - We investigated the effect of hyperthyroidism on the responses of small
      mesenteric resistance arteries to several contractile and dilator agents.
      Hyperthyroidism was established by feeding rats for 28 days with 5 mg/kg L
      thyroxine-containing rat chow. This treatment produced a stable hyperthyroid
      state, as indicated by the increased serum T4 levels (236 +/- 7 vs. 60 +/- 2; T4
      treated vs. control). Preparations of small mesenteric arteries were mounted in
      an isometric wire myograph. Subsequently, concentration-effect curves were
      determined for K+, Ca2+, methoxamine, phenylephrine, 5-hydroxytryptamine (5-HT),
      9,11-dideoxy-11 alpha, 9 alpha-epoxymethano-prostaglandin F2 alpha (U46619),
      methacholine and nitroprusside. Our results indicate that hyperthyroidism does
      not induce major changes in the sensitivity of isolated resistance vessels to K+,
      Ca+, the alpha-adrenoceptor agonist, methacholine and nitroprusside. Furthermore,
      neither the affinity of alpha-receptors for methoxamine, nor the alpha-receptor
      reserve was influenced by the hyperthyroid state of the animal. A clearly
      sensitizing influence of hyperthyroidism was found for the vasoconstrictor
      effects of both 5-HT (6.57 +/- 0.04 vs. 6.29 +/- 0.06; hyperthyroid vs. control)
      and the thromboxane A2 receptor agonist U46619 (6.78 +/- 0.13 vs. 6.30 +/- 0.09;
      hyperthyroid vs. control). Sensitization to both 5-HT and U46619 was abolished in
      the presence of N omega-nitro-L-arginine methylester HCl (L-NAME, 0.1 mM). 5-HT
      induced contractions in vessels from hyperthyroid rats were diminished by prior
      incubation with indomethacin (10 microM). The present results indicate that
      during hyperthyroidism resistance vessels are sensitized to both 5-HT and U46619.
      This sensitization involves the nitric oxide/L-arginine pathway and probably also
      certain steps in the cyclooxygenase pathway.

PMID- 8741172
TI  - Comparison of the effects of aminoguanidine and N omega-nitro-L-arginine methyl
      ester on the multiple organ dysfunction caused by endotoxaemia in the rat.
AB  - This study compares the effects of aminoguanidine, a relatively selective
      inhibitor of inducible nitric oxide (NO) synthase, and N omega-nitro-L-arginine
      methyl ester (L-NAME), a selective inhibitor of endothelial NO synthase, on
      hypotension and multiple organ dysfunction caused by endotoxaemia in the
      anaesthetised rat. In the sham-operated rats, L-NAME, but not aminoguanidine,
      caused a dose-dependent increase in blood pressure. Endotoxin caused hypotension,
      increased in plasma nitrite (an indicator of inducible NO synthase activity), and
      dysfunction of kidney, liver and pancreas. Treatment of endotoxic rats with
      aminoguanidine or L-NAME caused significant and sustained rises in blood
      pressure. The increase in plasma nitrite caused by endotoxin was inhibited by
      aminoguanidine, but not by L-NAME. Aminoguanidine, but not L-NAME, attenuated the
      renal, liver and pancreatic dysfunction caused by endotoxaemia. Thus, selective
      inhibition of inducible (aminoguanidine), but not endothelial NO synthase (L
      NAME) attenuates the circulatory failure and the multiple organ failure caused by
      endotoxaemia.

PMID- 8741173
TI  - Depressor action of L-threo-dihydroxyphenylserine in the rat nucleus tractus
      solitarii.
AB  - Microinjections of L-threo-dihydroxyphenylserine (L-threo-DOPS, 0.1-3 ng), a
      synthetic precursor amino acid of noradrenaline, into the medial area of the
      nucleus tractus solitarii produced dose-dependent depressor and bradycardic
      responses in anesthetized rats treated with or without i.p. 3
      hydroxybenzylhydrazine, a central inhibitor of L-aromatic amino acid
      decarboxylase. D-threo-DOPS (3 ng) produced no effect. L-Dihydroxyphenylalanine
      (L-DOPA) methyl ester (1 microgram), a competitive antagonist of L-DOPA,
      microinjected into the nucleus tractus solitarii, blocked the depressor and
      bradycardic responses to L-threo-DOPS itself produces vasodepressor actions
      without its conversion to noradrenaline, probably via a recognition site for L
      DOPA in the rat nucleus tractus solitarii.

PMID- 8741174
TI  - GR127935 is a potent antagonist of the 5-HT1-like receptor mediating contraction
      in the canine coronary artery.
AB  - The effects of the recently developed 5-HT1D receptor antagonist, GR127935 (N-[4
      methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol
      3-yl) [1,1,-biphenyl]-4-carboxamide), and those of the preferential human 5-HT1D
      alpha receptor antagonist, ketanserin, on the isometric contraction induced by 5
      hydroxytryptamine (5-HT) and sumatriptan in endothelium-denuded ring segments of
      canine coronary artery were analyzed. Sumatriptan mimicked 5-HT with lower
      potency but similar efficacy. GR127935 (1,3 and 10 nM) concentration dependently
      antagonized the contractions elicited by both agonists; only the 5-HT maximum was
      reduced. Ketanserin and mianserin (both at 1 microM) were inactive. These data
      strongly suggest that a 5-HT1D receptor mediates contraction in the dog coronary
      artery. The possibility that this 5-HT1D receptor resembles the cloned human 5
      HT1D beta subtype is discussed.

PMID- 8741175
TI  - [125I]S(-)-zacopride labels a novel 5-hydroxytryptamine sensitive recognition
      site in rat duodenum and ileum.
AB  - Autoradiographic binding studies using [125I]S(-)-zacopride (0.1 nM) identified
      non-5-HT3 specific binding sites (defined by 5-hydroxytryptamine (5-HT), 1.0
      microM) in the rat duodenum and ileum and some other peripheral tissues (adrenal
      gland, liver, stomach, kidney and spleen). In the rat duodenum and ileum,
      saturation studies with [125I]S(-)-zacopride indicated that the specific binding
      was saturable and of high affinity to an apparently homogenous population of
      binding sites (duodenum Bmax = 1.88 fmol/mg, Kd = 0.078 nM; ileum Bmax = 1.60
      fmol/mg, Kd = 0.071 nM). Competition studies with slices of either duodenum or
      ileum indicated that the pharmacology of the [125I]S(-)-zacopride recognition
      site in both tissues was comparable but differed from all 5-HT receptors and
      uptake sites reported to date. However, the [125I]S(-)-zacopride recognition site
      displayed some pharmacological and regional similarity to the 5-HT1P recognition
      site: The sensitivity of the [125I]S(-)-zacopride binding in the duodenum and
      ileum to GTP indicates that the radiolabelled recognition site may represent a
      functional G-protein coupled receptor.

PMID- 8741176
TI  - Effect of angiotensin AT2 and muscarinic receptor blockade on osmotically induced
      vasopressin release.
AB  - Recently, we have shown that angiotensin II-induced AT1 receptor-mediated
      vasopressin release can be potentiated by blockade of periventricular AT2
      receptors. In the present study, we investigated whether the AT2 receptor also
      exerts an inhibitory effect on osmotically induced vasopressin release. In
      addition, we tested the effect of the muscarinic receptor antagonist, atropine,
      on hyperosmolar saline-induced vasopressin release. Plasma vasopressin levels
      were determined 90 s after intracerebroventricularly applied hyperosmolar saline
      (0.2, 0.3 and 0.6 M, 5 microliters) with or without intracerebroventricular
      pretreatment with 1 nmol of the selective AT2 receptor antagonist, PD 123177 (1
      (4-amino-3-methylphenyl)methyl-5-diphenylacetyl-4,5,6,7-tetrahy dro- 1H
      imidazo[4,5-c]pyridine-6-carboxylic acid-2HCl), or with 15 nmol of the muscarinic
      receptor antagonist, atropine. PD 123177 potentiated 0.2 M saline-induced
      vasopressin release (4.7 +/- 0.8 pg/ml vs. 2.2 +/- 0.3 in vehicle-pretreated
      controls, P < 0.05), did not affect 0.3 M saline-induced vasopressin release (4.3
      +/- 0.7 pg/ml vs. 5.4 +/- 0.6 pg/ml in vehicle-pretreated controls) and reduced
      0.6 M saline-induced vasopressin release (10.0 +/- 2.3 pg/ml vs. 17.9 +/- 1.8
      pg/ml in vehicle-pretreated controls, P < 0.05). Pretreatment with atropine
      reduced 0.3 M (2.3 +/- 0.6 pg/ml vs. 5.4 +/- 0.9 pg/ml in vehicle-pretreated
      controls, P < 0.05) and 0.6 M saline-induced AVP release (4.0 +/- 1.5 pg/ml vs.
      18.4 +/- 2.4 pg/ml in vehicle-pretreated controls, P < 0.05) but did not affect
      0.2 M saline-induced vasopressin release (2.1 +/- 0.4 pg/ml vs. 3.2 +/- 0.8 pg/ml
      in vehicle-pretreated controls). Our results suggest that the low saline
      concentration-induced, AT1 receptor-mediated, vasopressin release is under
      inhibitory control by periventricular AT2 receptors. Following high saline
      concentrations, a muscarinic mechanism seems to be predominant on which AT2
      receptor stimulation acts in a facilitating manner.

PMID- 8741177
TI  - Loreclezole modulates [35S]t-butylbicyclophosphorothionate and [3H]flunitrazepam
      binding via a distinct site on the GABAA receptor complex.
AB  - The allosteric modulation of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) and
      [3H]flunitrazepam binding was utilized to evaluate the actions of loreclezole at
      the GABAA receptor complex in the rat brain. Loreclezole was observed to
      allosterically inhibit the binding of [35S]TBPS in a dose-dependent manner with
      micromolar potency (IC50 = 1 microM). Loreclezole was found to have an additive
      effect on neuroactive steroid modulation of [35S]TBPS binding, but merely
      potentiated the effect of Ro5-4864 (4"-chlorodiazepam) modulation of [35S]TBPS
      binding. These observations suggest that loreclezole modulates [35S]TBPS binding
      through a site independent of the neuroactive steroid and Ro5-4864 sites on the
      GABAA receptor complex. The enhancement of [3H]flunitrazepam binding to the
      benzodiazepine receptor by loreclezole as well as the effect of loreclezole on
      CL218872/[3H]flunitrazepam dose-response curves suggest that loreclezole does not
      act through the benzodiazepine site on the GABAA receptor complex, nor does it
      selectively modulate benzodiazepine receptor subtypes. The potency of loreclezole
      as and inhibitor of [35S]TBPS binding in rat brain was regionally dependent and
      GABA-sensitive. Loreclezole modulation of [35S]TBPS binding showed greater
      potency and GABA sensitivity in the cerebellum and thalamus when compared to
      other brain regions such as the cortex, hippocampus and striatum. This finding is
      consistent with previous reports of the selectivity of loreclezole for GABAA
      receptor complex's containing beta 2 and beta 3 subunits. These beta subunit
      isoforms predominate in the cerebellum and thalamus. Collectively the evidence
      suggests that loreclezole modulates [35S]TBPS and [3H]flunitrazepam binding
      through a site distinct from benzodiazepine, neuroactive steroid, Ro5-4864 and
      GABA sites on the GABAA receptor complex.

PMID- 8741178
TI  - Suppressive effect of N-(benzyloxycarbonyl)-L-phenylalanyl-L-tyrosinal on bone
      resorption in vitro and in vivo.
AB  - The suppressive effect of N-(benzyloxycarbonyl)-L-phenylalanyl-L-tyrosinal on
      bone resorption was examined in vitro and in vivo. This synthetic peptidyl
      aldehyde was found to be a potent and selective cathepsin L inhibitor in our
      screening for cysteine protease inhibitors. In the pit formation assay with
      unfractionated rat bone cells, 1.5 nM of this compound markedly inhibited
      parathyroid hormone-stimulated osteoclastic bone resorption. In addition,
      intraperitoneal administration of this peptidyl aldehyde (2.5-10 mg/kg) for 4
      weeks suppressed bone weight loss dose dependently in the ovariectomized mouse,
      experimental model of osteoporosis. Hydroxyproline measurement of the decalcified
      femurs from these ovariectomized mice suggested that this compound acts as a bone
      resorption suppressor through the inhibition of collagen degradation.

PMID- 8741179
TI  - Stereoselectivity of 8-OH-DPAT enantiomers at cloned human 5-HT1D receptor sites.
AB  - The cAMP responses of (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)
      and its enantiomers were measured at cloned human 5-HT1D alpha and 5-HT1D beta
      receptors in transfected C6-glial cells. R(+)-8-OH-DPAT demonstrated potent
      intrinsic activity (EC50 value: 30 nM) at 5-HT1D alpha receptor sites, its
      maximal effect being comparable to that of sumatriptan. Racemic 8-OH-DPAT and S(
      )-8-OH-DPAT showed similar agonist efficacy but were respectively 2 and 75 times
      less potent than R(+)-8-)OH-DPAT. This differs from the lack of stereoselectivity
      of the 8-OH-DPAT enantiomers for 5-HT1A receptors.

PMID- 8741180
TI  - Selective antagonism of human 5-HT1D and 5-HT1B receptor-mediated responses in
      stably transfected C6-glial cells by ketanserin and GR 127,935.
AB  - The antagonist effects of ketanserin and 2'-methyl-4'-(5-methyl-1,2,4)oxadiazol-3
      yl)-biphenyl-[4-carboxyli c acid 4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]
      amide (GR 127,935) were compared to naratriptan-induced inhibition of cAMP
      formation in C6-glial cell lines stably expressing human 5-HT1D or 5-HT1B
      receptor sites. Ketanserin demonstrated potent (pA2: 7.76), competitive
      antagonism of naratriptan-induced inhibition of forskolin (100 microM)-stimulated
      cAMP formation in C6-glial/5-HT1D cells. Whereas GR 127,935 was ineffective as an
      antagonist in these cells, it produced and intrinsic activity (pEC50: 6.98) that
      was sensitive to ketanserin (10 microM) blockade. Unlike ketanserin, GR 127,935
      potently antagonised the naratriptan response in C6-glial/5-HT1B cells while also
      depressing the maximum response. The differential antagonist effects of
      ketanserin and GR 127,935 on naratriptan responses elicited in C6-glial/5-HT1D
      and C6-glial/5-HT1B cells demonstrate these compounds do selectively block human
      5-HT1D and 5-HT1B receptors, respectively.

PMID- 8741181
TI  - Ursodeoxycholic acid inhibits the induction of nitric oxide synthase.
AB  - Ursodeoxycholic acid was recently recognized as an effective agent in the
      treatment of primary biliary cirrhosis. Since the beneficial effect of
      ursodeoxycholic acid therapy appears to be mediated in part by an immune
      mechanism, we evaluated the effects of ursodeoxycholic acid on the synthesis of
      nitric oxide (NO), elevated production of which could be important in the
      pathogenesis of autoimmunity. Ursodeoxycholic acid (0.1-1000 microM) inhibited NO
      production by bacterial lipopolysaccharide-activated J774 macrophages in a
      concentration-dependent fashion, but the cytotoxicity was also evident at higher
      concentrations (250 and 1000 microM). Ursodeoxycholic acid did not have any
      effect on the activity of NO synthase that had already been induced. Treatment
      with lipopolysaccharide led to a significant expression of NO synthase mRNA that
      was significantly reduced by ursodeoxycholic acid. Findings indicated that
      ursodeoxycholic acid inhibited NO synthesis by inhibiting the induction of NO
      synthase, rather than its catalytic activity. Ursodeoxycholic acid therapy may
      exert a beneficial effect, in part, by attenuating the production of NO.

PMID- 8741182
TI  - Functional coupling between metabotropic glutamate receptors and G proteins in
      rat brain membranes.
AB  - Functional activation of GTP-binding (G) proteins coupled with metabotropic
      glutamate receptors was evaluated in rat brain membranes. L-Glutamate stimulated
      the high-affinity GTPase activity in cerebral cortical, hippocampal, and striatal
      membranes with a mean concentration eliciting a half-maximal response (EC50) of
      4.8, 1.6, and 4.9 microM, respectively. The enzyme activity in cerebral cortical
      membranes was also stimulated by (2S, 1'S,2'S)-2-(carboxycyclopropyl)glycine (L
      CCG-I) with a mean EC50 of 0.90 microM, but not by L-2-amino-4-phosphonobutyrate
      (L-AP4) up to 10 microM. This method opens up a strategy for investigation of
      functional coupling between Group II metabotropic glutamate receptors and G
      proteins in native brain membranes.

PMID- 8741184
TI  - Desipramine treatment differently down-regulates beta-adrenoceptors of freshly
      isolated neurons and astrocytes.
AB  - Eight days' desipramine administration (16 mg/kg per day i.p.) to rats resulted
      in a significant decrease in the density of beta-adrenoceptors in neuronal and
      astroglial cells from rat forebrain and cerebellum without modification of their
      corresponding affinity. beta-Adrenoceptor subtypes, beta 1 and beta 2, which
      coexist in neurons and astrocytes, are differently distributed in the brain and
      differently modified by desipramine administration which down-regulates beta 1
      adrenoceptor in forebrain neurons and astrocytes and beta 2-adrenoceptor in
      cerebellum neurons. This down-regulation affects the predominant subtype, beta 1
      or beta 2, of the relevant structure. Astroglial and neuronal beta-adrenoceptors
      are differently coupled to G-proteins. Only neuronal cells contain the high
      affinity conformational state of the beta-adrenoceptors which is sensitive to
      GTP. The percentage of neuronal receptors in the high-affinity state differs
      according to brain area. Desipramine treatment decreases the neuronal density of
      both cerebellar high- and low-affinity sites and only the forebrain high-affinity
      site. The desipramine effects are thus subtype-dependent and differ between the
      two brain areas selected.

PMID- 8741183
TI  - Subtype selectivity of a new alpha 1-adrenoceptor antagonist, JTH-601: comparison
      with prazosin.
AB  - The existence of alpha 1-adrenoceptors with low affinity for prazosin (alpha 1L
      group: alpha 1L and alpha 1N subtypes) has been proposed in addition to alpha 1
      adrenoceptor subtypes with high affinity for prazosin (alpha 1H group: alpha 1A,
      alpha 1B and alpha 1D subtypes). A newly synthesized alpha 1-adrenoceptor
      antagonist, JTH-601 (N-(3-hydroxy-6-methoxy-2,4,5-trimethylbenzyl)-N-methyl-2-(4
      hydro xy-2-isopropyl-5-methyl-phenoxy) ethylamine hemifumarate) showed
      approximately a 10 times higher affinity for the alpha 1L group, a similar
      affinity for the alpha 1A subtype, but a more than 10 times lower affinity for
      the alpha 1B and alpha 1D subtypes when compared with prazosin. These results
      provide a further pharmacological evidence that alpha 1-adrenoceptors with low
      affinity for prazosin exist in addition to those with high affinity for prazosin,
      suggesting that JTH-601 may be useful for characterising the alpha 1-adrenoceptor
      subtypes.

PMID- 8741185
TI  - delta-Opioid receptor: the third extracellular loop determines naltrindole
      selectivity.
AB  - Human delta/mu-opioid receptor chimeras were constructed to determine the role of
      the second and third extracellular loops in alkaloid ligand selectivity.
      Exchanging the third extracellular loop of the delta-opioid receptor with that of
      the mu-opioid receptor dramatically decreased the affinity of naltrindole, but
      not that of morphine. The results suggest that different domains of the opioid
      receptor are involved in the binding of naltrindole and morphine.

PMID- 8741186
TI  - A T1-weighted rapid three-dimensional gradient-echo technique (MP-RAGE) in
      preoperative MRI of intracranial tumours.
AB  - Our purpose was to determine the value of a T1-weighted rapid three-dimensional
      gradient-echo technique in preoperative MRI of brain tumours. We examined 30
      patients with intracranial tumours who underwent neurosurgery, using T1-weighted
      magnetisation-prepared rapid gradient-echo (MP-RAGE) and axial T1-weighted spin
      echo (SE) sequences, both before and after contrast medium (Gd-DTPA). Signal and
      contrast behaviour of anatomical and pathological structures were assessed with
      regions-of-interest (ROI) and visual inspection. Imaging results were compared
      with operative results. In 5 cases tumours and anatomical structures were
      segmented in MP-RAGE data sets. The MP-RAGE sequence considerably improved
      delineation of grey and white matter and small anatomical structures (vessels,
      cranial nerves), and significantly reduced flow artefacts. Contrast behaviour of
      tumours was similar with both techniques. Correlation of imaging with the
      operative results confirmed the reliability of the MP-RAGE sequence. Segmentation
      of MP-RAGE data sets allows three-dimensional display, which enables one to
      document the relevant information on a few images in selected cases.

PMID- 8741187
TI  - MRI in detection of brain metastases at initial staging of small-cell lung
      cancer.
AB  - We prospectively investigated 40 patients with small-cell carcinoma of the lung
      (SCLC) for signs of brain metastasis by neurological examination and MRI of the
      brain, to determine the significance of MRI for staging. MRI could not be
      completed in one patient, who was excluded from the study. The MRI studies of the
      remaining patients showed no abnormalities in 12, cerebral infarcts in 2 and
      brain metastases in 11 patients, of whom 3 no relevant symptoms. Nonenhancing
      white matter lesions were found in 14 patients. In 3 of the 4 patients with an
      abnormal neurological examination at diagnosis, nonenhancing white matter lesions
      later developed into contrast enhancing lesions compatible with brain metastases;
      in 2, this occurred during the course of the chemotherapy. MRI did not change the
      clinical staging in patients with asymptomatic brain metastases.

PMID- 8741189
TI  - Development of fat within a meningioma.
AB  - We report a tentorial meningioma containing fat. Multiple areas of fatty density
      or intensity in the tumour were seen on CT and MRI, which corresponded
      histologically to lipomatous components. CT 10 years previously had demonstrated
      a smaller tumour without evidence of fatty components. We found only five cases
      in the literature in which fatty density was demonstrated within a meningioma on
      CT and a lipomatous component histologically proved. Xanthomatous change, with
      lipid in tumour cells, causes decrease in density on CT, but not to the levels of
      fat. As both lipomatous components and xanthomatous change show similar intensity
      on MRI, CT can be helpful in differentiating these two conditions. To our
      knowledge, our case is the only one in which the advent of fatty tissue was
      confirmed during follow-up.

PMID- 8741188
TI  - Primary cranial vault lymphoma mimicking meningioma.
AB  - Primary lymphomas of the cranial vault are rare; only six patients have been
      described in the literature. We report a 75-year-old woman who was admitted to
      our hospital after a focal seizure. CT showed a homogeneous mass which, on
      contrast enhancement, was similar to a meningioma. The tumour was excised and
      found to be a centroblastic, centrocytic non-Hodgkin's lymphoma. Treatment was
      completed with radiotherapy and chemotherapy.

PMID- 8741190
TI  - In vitro delineation of human brain-stem anatomy using a small resonator:
      correlation with macroscopic and histological findings.
AB  - Our purpose was to investigate the potential of an experimental animal coil using
      a commercial MRI unit to delineate the anatomical structure of the human brain
      stem. Three formaldehyde-fixed brain-stem specimens were examined by MRI and
      sectioned perpendicular to their longitudinal axis. The images were compared with
      gross anatomy and myelin-stained histological sections. Fibre tracts and nuclei
      which were not evident on examination of the unstained specimen were readily
      identified by MRI. Due to its inherent grey/white matter contrast, MRI with a
      high-resolution coil delineates anatomical structures in a way comparable to the
      myelin-stained histological sections. However, pigmented structures, readily
      visible on examination of the unstained specimen were discernible on neither MRI
      nor on myelin-stained sections. The excellent anatomical detail and grey/white
      matter contrast provided by these images could make MRI a useful adjunct to the
      pathologist investigating brain disease.

PMID- 8741191
TI  - Reliability of visual inspection for detection of volumetric hippocampal
      asymmetry.
AB  - Volumetric measurement of the hippocampus is of use in localisation of lesions
      causing focal epilepsy and in lateralisation of epilepsy due to mesial temporal
      sclerosis. However, it is time consuming and requires specialised equipment.
      Hence, we compared volumetric measurement with visual detection of hippocampal
      asymmetry by five trained observers. MRI studies of 19 neurologically normal
      subjects and of 34 consecutive patients with epilepsy and hippocampal volume
      ratios below the lowest normal value were employed. Agreement between visual and
      quantitative diagnoses was 59% for all subjects (kappa = 0.38) and 65% for those
      with volumetric hippocampal asymmetry. Disagreements in visual and volumetric
      lateralisation of hippocampal asymmetry were relatively uncommon. Visual
      estimates of the extent of hippocampal involvement and the observers' confidence
      in the diagnosis influenced the accuracy of visual inspection. However,
      discordance in diagnoses occurred even when confidence in the visual diagnosis
      was high. Reliable visual detection occurred for hippocampal volume ratios below
      0.7, suggesting that visual determination of hippocampal asymmetry is of greatest
      clinical value in the lateralisation of seizure foci in patients already selected
      for the presence of intractable temporal lobe epilepsy. Volumetric measurements
      are particularly important if hippocampal asymmetry is used for seizure
      localisation in groups of patients with temporal or extratemporal epilepsy.

PMID- 8741192
TI  - CT and MRI in iatrogenic and sporadic Creutzfeldt-Jakob disease: as far as
      imaging perceives.
AB  - Creutzfeldt-Jakob Disease (CJD), an invariably fatal dementing illness, affects
      patients in middle and old age (sporadic form). However, the association of CJD
      with certain treatments (iatrogenic form) has been described in younger patients.
      The clinical onset of the two forms seems to differ; in the iatrogenic form a
      high frequency of the ataxic CJD variant has been reported. Nowadays, a
      definitive diagnosis of CJD is exclusively histological. We present five cases of
      CJD, one sporadic and the others iatrogenic, following dura mater grafts and
      analyse their CT and MRI features. CT typically demonstrates brain atrophy,
      generally progressive, but in sporadic CJD midfield MRI also showed abnormal
      signal, with predominant deep grey matter involvement. The use of narrow windows
      with proton-density sequences may reveal subtle cortical signal abnormalities not
      clearly visible with conventional windows. The early demonstration of these
      changes, in the appropriate clinical context, may suggest CJD and this supports
      the use of mid- or high magnetic fields in the diagnosis of CJD and other forms
      of dementia. In our cases of iatrogenic CJD, low-field MRI did not reveal more
      than the progressive atrophy displayed by CT, and raises the question on the one
      hand of possible differences, based on imaging, from the sporadic form, and on
      the other of the lack of sensitivity of low-field magnets to signal changes in
      CJD.

PMID- 8741193
TI  - Neuroradiological findings in primary progressive aphasia: CT MRI and cerebral
      perfusion SPECT.
AB  - Primary progressive aphasia (PPA) is defined as progressive decline in language
      for 2 or more years with preservation of activities of daily living and general
      cognitive functions. Whereas the clinical features of this syndrome have been
      well documented, the neuroradiological findings have not been studied
      systematically. We studied 13 patients with PPA retrospectively: 10 underwent CT,
      12 MRI and 12 cerebral perfusion studies using 99mTc-HMPAO SPECT.CT and MR images
      were scored for focal atrophy by two independent assessors. Initial qualitative
      assessment of SPECT images was confirmed by quantitative analysis. CT was normal
      in 5 patients. Focal atrophy, affecting predominantly the left temporal lobe, was
      seen in 4 of 10 patients on CT, and 10 of 12 on MRI. Atrophy was localised
      primarily to the superior and middle temporal gyri on MRI. All 12 patients who
      underwent SPECT had unilateral temporal lobe perfusion defects, in 2 patients of
      whom MRI was normal. CT is relatively insensitive to focal abnormalities in PPA;
      MRI and SPECT are the imaging modalities of choice. MRI allows accurate, specific
      localisation of atrophy within the temporal neocortex. SPECT may reveal a
      functional decrease in cerebral perfusion prior to establishment of structural
      change.

PMID- 8741194
TI  - Transient ipsilateral blood flow reduction in the thalamus and cerebral cortex
      after pontine infarction.
AB  - Remote cerebral hypoperfusion associated with pontine lesions is rare. We
      describe a patient who showed transient ipsilateral hypoperfusion in the thalamus
      and cerebral cortex after a pontine infarct. This resolved within 8 days after
      onset. Anatomical considerations strongly suggested involvement of the
      cerebellothalamocortical pathway in this case.

PMID- 8741195
TI  - A simple method for localising single-photon emission computed tomographic images
      on an anatomical template.
AB  - We introduce a simple method for localising brain images an anatomical templates.
      Our method does not need expensive software or hardware and may be useful for
      clinical investigation.

PMID- 8741196
TI  - Initial clinical experience with spiral CT and 3D arterial reconstruction in
      intracranial aneurysms and arteriovenous malformations.
AB  - We studied 32 consecutive patients with known or suspected cerebrovascular
      abnormalities studied with spiral CT following a intravenous bolus injection of
      iodinated contrast medium with a power injector. Flow was 3 or 4 ml/s. In an
      attempt to define the appropriate delay time and scan duration a cranial angio-CT
      without table increment was performed on 10 patients. Enhancement was measured by
      manually placed regions of interest within the left middle cerebral artery and
      the inferior sagittal sinus. All patients except one had intraarterial
      angiography (DSA) for comparison. In 6 patients with an arteriovenous
      malformation (AVM) follow-up was possible after one and/or two embolisation
      procedures. These patients had plain and contrast-enhanced spiral CT. The
      diagnosis was aneurysm in 9 (8 berry aneurysms, one giant fusiform aneurysm), AVM
      in 13 (all supratentorial) and traumatic arteriovenous fistula in one. In 9
      patients there were no detectable pathological vascular findings. After 3D
      reconstruction the size (between 5 and 28 mm), location and the relationship to
      the parent vessel of the aneurysms, the extent of the AVMs and the distribution
      of the embolisation material could be demonstrated clearly. The main feeding
      vessel(s), nidus and draining veins were reliably shown. The decreased extent of
      the AVMs after embolisation was clearly demonstrated. There was no difference in
      diagnosis when DSA and 3D-CT were compared by two independent radiologists. We
      consider arterial spiral CT with 3D reconstruction to have the potential of
      offering important diagnostic information for the treatment of intracranial AVMs
      and aneurysms.

PMID- 8741197
TI  - Anterior cranial fossa dural arteriovenous fistula with a varix mimicking an
      anterior communicating artery aneurysm.

PMID- 8741198
TI  - Intracranial tumors in children: small single-voxel proton MR spectroscopy using
      short- and long-echo sequences.
AB  - We report preliminary experience using single-voxel, proton MR spectroscopy (MRS)
      employing small voxels of interest, in combination with short and long echo-time
      protocols, for the assessment of primary intracranial tumors in children. We
      examined 23 children with primary intracranial tumors detected by MRI, and 32
      controls with similar ages, using MRS on a 1.5 T system. Localized single-voxel
      (3.7 +/- 1.3 cc) proton spectra were obtained with short-echo (2,000/18),
      stimulated-echo (STEAM) and long-echo (2,000/270) spin-echo (PRESS) protocols.
      All spectra were evaluated qualitatively; 10 tumor and 19 control spectra were
      processed for peak area quantification. Small voxels of interest were able to
      account for tissue heterogeneity. Combined acquisition of short- and long-echo
      spectra increased the number of detectable metabolites. The solid portion of all
      tumors exhibited reduced N-acetyl-aspartate (NAA), strong contribution from
      cholines (Cho) and inositols or glycine, minimal presence of total creatine
      (tCr), enhanced broad mobile lipid resonances and accumulated lactate. Calculated
      selected metabolite ratios of Cho/tCr and Cho/NAA were substantially increased
      from control values. The cystic portions of the masses showed only lipid and
      lactate peaks.

PMID- 8741199
TI  - Minor changes on cranial MRI during treatment in children with acute
      lymphoblastic leukaemia.
AB  - Cranial MRI was used to study treatment-related changes in children undergoing
      therapy for acute lymphoblastic leukaemia (ALL) or lymphoma. Nineteen children
      (18 with ALL, 1 with lymphoma) underwent MRI at the beginning of treatment and at
      intervals during it, to a total of 105 imaging studies and a minimum of 3 per
      case. Nine patients had finished all therapy, all received consolidation
      treatment. No patient had central nervous system (CNS) leukaemia at diagnosis or
      developed a CNS relapse. Mild treatment-related white matter changes were
      observed in only 2 patients after consolidation therapy with three 5 g/m2 pulses
      of intravenous methotrexate. Transient enlargement of the ventricles and cortical
      sulci was observed in 13 patients, always temporally related to steroid
      treatment. These preliminary data suggest that treatment-related white matter
      changes are rare and no routine MRI follow-up is needed during treatment in
      asymptomatic children after a baseline assessment.

PMID- 8741200
TI  - Reye's syndrome with cortical laminar necrosis: MRI.
AB  - Serial MRI findings are described in two patients with Reye's syndrome,
      demonstrating diffuse cortical and white matter changes. In the acute stage, T2
      weighted images showed subtle but definite laminar high signal and contrast
      enhanced T1-weighted images laminar enhancement, along the entire cerebral cortex
      bilaterally. In the chronic stage, unenhanced T1-weighted images showed diffuse
      cortical laminar high signal. These characteristic MRI features seemed very
      similar to those of laminar cortical necrosis in hypoxic brain damage. MRI also
      displayed delayed white matter changes with cerebral atrophy.

PMID- 8741201
TI  - MRI of orbital hydroxyapatite implants.
AB  - Our aim was to use MRI for the postsurgical assessment of a new form of
      integrated orbital implant composed of a porous calcium phosphate hydroxyapatite
      substrate. We studied ten patients 24-74 years of age who underwent enucleation
      and implantation of a hydroxyapatite ball; 5-13 months after surgery, each
      patient was examined by spinecho MRI, with fat suppression and gadolinium
      enhancement. Fibrovascular ingrowth was demonstrated in all ten patients as areas
      of enhancement at the periphery of the hydroxyapatite sphere that extended to the
      center to a variable degree. The radiologist should aware of the MRI appearances
      of the coralline hydroxyapatite orbital implant since it is now widely used
      following enucleation. MRI is a useful means to determine successful
      incorporation of the substrate into the orbital tissues. The normal pattern of
      contrast enhancement should not be mistaken for recurrent tumor or infection.

PMID- 8741202
TI  - Inner ear malformations in patients with sensorineural hearing loss: detection
      with gradient-echo (3DFT-CISS) MRI.
AB  - The sensitivity of different MRI sequences in the detection of inner ear
      malformations in patients presenting with sensorineural hearing loss (SNHL)
      and/or vertigo was evaluated. We studied 650 patients presenting with SNHL and/or
      vertigo, clinically not suspected of having inner ear malformations. The
      sensitivity of T1-weighted, Gd-enhanced T1-weighted and (when available) T2
      weighted spin-echo images, and three-dimensional Fourier transformation
      constructive interference in steady state (3DFT-CISS) gradient-echo images, to
      unexpected malformations was assessed. Inner ear malformations were found in 15
      (2.3%) of these patients. Enlargement of the endolymphatic duct and sac was the
      most frequent malformation, found in 11 patients. The 3DFT-CISS images showed all
      lesions; the other sequences were less sensitive and the pathology was missed,
      partially or only retrospectively seen in 11 of the 15 patients. Therefore, in
      addition to the routine unenhanced and Gd-enhanced T1-weighted and T2-weighted
      images, thin gradient-echo (3DFT-CISS) images are necessary to detect all
      clinically unexpected inner ear malformations in patients presenting with vertigo
      and/or SNHL.

PMID- 8741203
TI  - CT of submandibular gland sialolithiasis.
AB  - We emphasise the importance of high-resolution CT with reconstruction in the
      demonstration of submandibular gland (SMG) sialolithiasis and its role in
      monitoring treatment. We studied 76 patients with swollen and tender SMG, some
      with fever. They underwent conventional radiography, sonography (US) and high
      resolution CT with reconstructions. Conventional radiographs demonstrated single
      stones in 29 patients. Axial CT, before reconstructions, demonstrated single
      stones in 63 patients and multiple stones in another 5. Following CT
      reconstructions, multiple stones were demonstrated in 37 patients. On US stones
      were diagnosed in only 33 patients, and multiple stones in only 1. All 68
      patients with stones shown on imaging and 2 without stones underwent surgery,
      with good clinical results. Total removal of the SMG and its duct was performed
      in patients with multiple stones, chronic inflammatory changes in the SMG, or a
      solitary stone in the SMG or deep in the duct. A small incision for removal of a
      solitary stone in the distal aspect of Wharton's duct was performed in 15
      patients, with excellent clinical results. Another 14 patients with multiple
      salivary gland stones, diagnosed on CT reconstructions, did not improve following
      this procedure and needed further surgery; clinical improvement occurred
      following excision of the SMG and Wharton's duct. Histological examination in all
      of these confirmed the presence of additional stones. Conservative anti
      inflammatory treatment was recommended for 6 patients in whom CT reconstructions
      did not demonstrate stones.

PMID- 8741204
TI  - Histological changes in brain tissue and vasculature after intracarotid infusion
      of organic solvents in rats.
AB  - Organic solvents, such as ethanol or dimethyl sulphoxide (DMSO), have been used
      in liquid embolic agents. To investigate the effects of these solvents on the
      cerebral blood vessels and cerebral tissue, we subjected Wistar rats weighing 250
      300 g to internal carotid artery infusion of 0.2 ml diluted ethanol (10%, 40% or
      70%) or anhydrous DMSO (100%). Some rats were sacrificed 5 min after the infusion
      and the remainder at 10 days. Rats injected with ethanol at high concentration or
      DMSO showed extensive exudation of Evans blue at the site of injection 5 min
      after infusion, together with full-thickness necrosis of the wall of vessels and
      swelling of brain cells. In contrast, rats injected with 10% or 40% ethanol
      solution showed necrosis of only the intimal layer and partial necrosis of the
      medial layer and no brain swelling was observed. These findings suggest that
      ethanol at low concentration can be used as a relatively safe solvent for liquid
      embolic substances.

PMID- 8741205
TI  - Investigation of malignant hyperthermia susceptibility in Denmark.

PMID- 8741206
TI  - Sympathetic reflex regulation of the peripheral circulation in humans.
AB  - Animal studies have firmly demonstrated the importance of cardiac
      mechanosensitive- and chemosensitive afferents in the sympathetic reflex
      regulation of the peripheral circulation. However, the precise role played by
      these afferents in the reflex control of the cardiovascular system in conscious
      humans is controversial. The main focus of this work is to test the role played
      by these afferents in humans. An unequivocal, simple answer cannot be given, but
      several important conclusions can be drawn. During orthostatic stress, it seems
      that the baroreflexes regulate not only vascular resistance but also capillary
      filtration. Mild orthostatic stress caused reflex increases in sympathetic
      vasomotor tone in both skeletal muscle and subcutaneous tissue in both arm and
      leg, which indicates that the cardiopulmonary mechanoreceptors do play some role
      in autonomic adjustments to orthostatic stress. On the other hand, the central
      pieces of evidence linking the reflex response to orthostatic stress only to
      ventricular mechanoreceptor deactivation are negated; the orthostatically-induced
      increase in sympathetic vasomotor tone is not attenuated by ventricular
      deafferentation. Normal orthostatic-induced increase in sympathetic nerve
      activity appears to be dependent mainly on the sino-aortic baroreceptors. But the
      ventricular mechanoreceptors may play a role, because orthostatic stress causes a
      larger than normal fall in arterial pressure in heart transplant recipients. The
      role played by chemically sensitive ventricular afferents also seems to be less
      important than previously thought, because stimulation of these afferents elicits
      only localised vasodilation (the forearm) and does not produce hypotension.
      Ventricular afferents are thus unlikely to be as important in humans as in
      animals. Nonetheless, that ventricular afferents, in certain special settings,
      are able to induce e.g. generalised vasodilation and hypotension cannot be
      excluded.

PMID- 8741207
TI  - Drug related hospital admissions in subspecialities of internal medicine.
AB  - It is well established in the literature that adverse drug reactions (ADRs) and
      drug non-compliance contribute substantially to the admissions at medical wards.
      Some important questions, however, remain unanswered. The purpose of this thesis
      was to characterise the drug-related hospital admissions (DRH) and to assess the
      magnitude of the problem seen in relation to the demographic parameters and drug
      use of the background population. In addition, an attempt was made to reduce the
      DRH incidence by an intervention program. The scope of the study program was
      adverse drug reactions, intended self-poisoning, non-compliance, underdosing and
      interactions. The material included 1999 admissions to six departments of
      internal medicine at Odense University Hospital. The patients were reviewed
      prospectively, while they were still in the wards, but use of standardised
      criteria fOR assessment of drug-ADR causality. With inclusion of a definite,
      probable and possible causal relationship, ADRs and toxic reactions were found as
      an important factor in 8.4% of all admissions. The incidense of ADR related
      admissions was 400 per 100,000 per year for the background population as a whole,
      but showing a strong increase with age. The drug-specific ADR incidences were
      generally small compared to the drug sales figures. Non-compliance contributed to
      2.0% of admissions with diuretics and anti-asthmatics as the drugs most
      frequently involved. Two departments were re-investigated after an intervention
      program, primarily targetting general practitioners. The over-all incidence of
      DRHs was unaffected by the intervention, but the subset classified as avoidable
      DRHs showed a significant decline. The case material was subject to a blinded
      evaluation by an external peer group using the same criteria as the
      investigators. There was no indication that the observed decline in avoidable
      DRHs should be explained by a shift in the investigators' assessment of cases. It
      was concluded that the intervention probably had a specific effect on avoidable
      DRHs. Admissions caused by adverse ractions to over-the-counter remedies, usually
      salicylates, were characterised by a particularly inappropriate use of drugs,
      suggesting that the public may also be a suitable target for interventions. In
      1990 the author established the Odense PharmacoEpidemiologic Database (OPED), a
      research registry with person-identifiable data on computerised refund claims
      from Funen County. The registry was validated by a cohort study on the
      association of non-steroidal antiinflammatory drugs (NSAID) and admission for
      severe upper gastrointestinal bleeding (UGB). All 31,503 recorded NSAID users in
      Odense during a 19 month period and a control cohort were studied. For both
      cohorts we obtained data on admissions caused by UGB and other diagnosis- and
      prescription-data that would be relevant for confounder control. The standardised
      incidence ratio was 5.5, controlled for age, sex and previous peptic ulcer
      episodes. A multivariate analyse revealed a number of other risk factors, but no
      other important confounders. The standardised incidence of UGB was particularly
      high during the first month of NSAID therapy. The size of the data set permitted
      an estimate of excess risk within various patient categories. NSAID users over 75
      years of age or with a previous peptic ulcer episode had particularly high excess
      risks. The utilization pattern of NSAIDs was surprisingly sporadic and appeared
      to favour a high UGB rate for a given sales volume. It is pointed out that
      individualised dispensing data may be an important tool in future endeavors to
      control DRH incidences. The data may be used for generating or confirming
      hypotheses on unknown and suspected ADRs, for studies on risk factors of ADRs,
      for characterising the population's drug utilization, for identifying objects for
      interventions and for monitoring the effect of interventions.

PMID- 8741208
TI  - Left and right ventricular volumes determined by magnetic resonance imaging.

PMID- 8741209
TI  - Mechanism and treatment of diarrhoea due to Vibrio cholerae and Escherichia coli:
      roles of drugs and prostaglandins.
AB  - The primary objectives of these studies were to determine the clinical efficacy
      and safety of the potential antisecretory and antimicrobial drugs in the
      treatment of diarrhoea due to Vibrio cholerae and enterotoxigenic Escherichia
      coli (ETEC). The drugs evaluated were chlorpromazine (CPZ), nicotinic acid,
      berberine, indomethacin, chloroquine, tetracycline, furazolidone, and bioflorin.
      Additionally, the role of prostaglandins (PGs) in the pathogenesis of cholera
      diarrhoea has been studied. The drug studies were carried out as placebo
      controlled, randomized clinical trials in patients with active diarrhoea due to
      vibrio cholerae and ETEC. All patients received intravenous (i.v.) or oral
      rehydration solutions (ORS), but no other medications except the study drugs.
      Results indicate that CPZ (1 mg/kg or 4 mg/kg), berberine (200 mg), and nicotinic
      acid (2 g) all reduced stool volumes from 30% to more than 50% in diarrhoeal
      patients without significant side effects. It appeared that berberine was more
      effective in ETEC diarrhoea than in cholera. However, chloroquine, indomethacin,
      clonidine, and bioflorin had no clinically useful effects. Among the
      antimicrobial agents, a single dose of tetracycline was found to be effective in
      cholera, because the drug significantly (p < 0.05) reduced the total stool volume
      from 20.9 +/- 15.9 to 10.5 +/- 8.6 (liters in 6-days, mean +/- SD) compared to
      furazolidone. Drugs other than antimicrobial and antisecretory agents were also
      evaluated in the treatment of cholera. It has been shown that treatment with
      bioflorin, which is a bacterial preparation of lyophilized Streptococcus faecium,
      did not significantly (p > 0.05) reduce fluid-loss in cholera. Additional studies
      in animals indicated that treatment with short chain glucose polymers, alone or
      in combination with a chloride blocking agent, anthracene-9-carboxylic acid
      (A9C), significantly reduced intestinal secretion in a rat model of secretory
      diarrhoea. For the first time it was demonstrated that jejunal prostaglandin (PG)
      E2 concentrations were significantly increased during acute cholera and
      correlated with the volumes of stool and duration of diarrhoea. Furthermore, it
      was shown that treatment with indomethacin, a potent inhibitor of PG synthesis,
      significantly reduced jejunal PGE2 output in adults with acute cholera, in
      addition to net secretion of water and electrolytes. In summarizing the results,
      it is concluded that: (1) CPZ, berberine, and nicotinic acid are potential
      antidiarrhoeal agents, (2) PGs are involved in the pathogenesis of cholera, (3)
      tetracycline and furazolidone are effective antimicrobial agents in cholera, (4)
      and glucose short-chain polymers (used with the chloride blocking agent,
      anthracene-9-carboxylic acid) are better sources of carbohydrates in oral
      rehydration solutions.

PMID- 8741210
TI  - Biochemical, virological and histopathological changes in Danish blood donors
      with antibodies to hepatitis C virus.
AB  - BACKGROUND: Previous studies have indicated that the presence of antibodies to
      Hepatitis C virus (HCV) is indicative of current HCV infection irrespective of S
      alanine aminotransferase (S-ALT) values. STUDY DESIGN AND METHODS: Over three
      years, all confirmed anti-HCV-positive blood donors form the Blood Banks of
      Copenhagen County were consecutively evaluated. Seven women and 14 men with a
      median age of 34 years were included. Serum HCV-RNA was measured with an in-house
      developed single PCR. Liver biopsies were classified according to standard
      criteria. RESULTS: All were asymptomatic at presentation with no history of liver
      disease. Previous intravenous drug abuse and/or tattooing were identified in 16.
      Seventeen blood donors were evaluated biochemically and histologically. Serum HCV
      RNA was detectable in 14, all of whom had histopathological changes in their
      liver biopsy including chronic active hepatitis and active cirrhosis. Twelve of
      the 14 HCV-RNA-positive donors had elevated S-ALT. In the three HCV-RNA-negative
      donors, S-ALT was normal. Two of these had normal liver biopsies, whereas the
      third had minimal changes. CONCLUSION: To diagnose and evaluate the activity of
      chronic HCV infection, liver biopsy and HCV-RNA assessment are essential in
      confirmed anti-HCV-positive individuals irrespective of symptoms and S-ALT
      levels.

PMID- 8741211
TI  - Integration of titin into the sarcomeres of cultured differentiating human
      skeletal muscle cells.
AB  - Titin is amongst the first sarcomeric proteins to be detected in the process of
      myofibrillogenesis of striated muscle. During embryogenesis this high molecular
      weight protein is initially observed in a punctate staining pattern in
      immunohistochemical studies, while during maturation titin organizes into a cross
      striated pattern. The dynamic process of titin assembly up to its integration
      into the sarcomeres of cultured human skeletal muscle cells has been studied in
      subsequent stages of differentiation with antibodies to four well-defined titin
      epitopes. Since in maturated muscle cells these epitopes are clearly
      distinguishable on the extended titin molecule we wondered how these epitopes
      reorganize during myofibrillogenesis, and whether such a reorganization would
      reveal important clues about its supramolecular organization during development.
      Immunofluorescence staining of postmitotic mononuclear myoblasts indicate that
      the investigated epitopes of the titin molecule are displayed in a punctate
      pattern with neighboring, but clearly separate spots in the cytoplasm of the
      cells. During elongation and fusion of the cells, these titin spots associate
      with stress fiber-like structures to finally reach their position at either the Z
      line, the A-I junction or the A-band. We propose that during this transition the
      large titin molecule is unfolded, with the amino terminus of the molecule
      migrating in the direction of the Z-line and the carboxy terminus moving towards
      the M-line. In maturated, fused myotubes the final cross-striated patterns of all
      investigated titin epitopes are observed. While this process of unfolding of the
      titin molecule progresses, other compounds of the Z-line and the A-band migrate
      to their specific positions in the nascent sarcomere. A-band components such as
      sarcomeric myosin and C-protein, are also observed as dot-like aggregates during
      initial stages of muscle cell differentiation and organize into a cross-striated
      pattern in the sarcomere virtually simultaneously with titin. The Z-line
      associated component desmin organizes into a cross-striated pattern at a later
      stage.

PMID- 8741212
TI  - Distribution of actin and tubulin in outer hair cells isolated from developing
      rat cochlea: a quantitative study.
AB  - In the organ of Corti, outer hair cells (OHCs) are sensory effectors responsible
      for the high sensitivity and sharp tuning of the cochlea. Whilst the distribution
      and organization of actin and tubulin in adult OHCs have been extensively
      studied, less is known about developing OHCs. In this study we use a quantitative
      cytometric approach on rat isolated OHCs to measure the distribution of these
      cytoskeletal proteins from the first stages of development (postnatal day 5) to
      the adult stage. We report a general decrease in both actin and tubulin
      concentrations during OHC maturation. Actin first decreases in the apical domain,
      and then in the medio-basal domain. In the apical domain, this could be related
      to the physiological reduction in the number of stereocilia occurring during
      ciliogenesis. In the medio-basal domain, the decrease, accompanied by a
      redistribution of actin toward the lateral wall, is possibly related to the
      general reorganization of cytoplasmic organelles, to the maturation of the
      cortical lattice, and to cell growth. Tubulin concentration decreases regularly
      in both the apical and the medio-basal domains. This developmental change in
      tubulin concentration could be due to the regression of the kinocilium that
      occurs by the end of ciliogenesis, and, as argued for actin, to the general
      reorganization of cytoplasmic organelles, and to cell growth.

PMID- 8741213
TI  - Expression of two FGF-2 isoforms in pancreatic acinar cells (AR4-2J).
      Intracellular localization and role in the regulation of the extracellular matrix
      biosynthesis.
AB  - Fibroblast growth factor (FGF-2) is a multifunctional growth factor. In cells
      producing this factor, FGF-2 is synthesized as different molecular weight
      isoforms lacking the signal peptide sequence for secretion. All forms are highly
      concentrated in cells. The presence of a nuclearization signal sequence in some
      isoforms suggests the involvement of these isoforms in cell functions bypassing
      the cell surface receptors. Our aims were to better define the intracellular
      localizations of the FGF-2 isoforms by immunocytochemistry and confocal
      microscopy and to analyze whether these isoforms were involved in the expression
      of extracellular matrix (ECM) components. We chose the pancreatic acinar cell
      line AR4-2J since it does not synthesize FGF-2. These cells were retrovirally
      transfected by point-mutated FGF-2 cDNAs. The cell lines obtained produced either
      the 18 kDa form (A5 cells) or the 22.5 kDa form (A3 cells). In A5 cells, the 18
      kDa form was found in the cytoplasm, on the cell surface reflecting its
      secretion, and in the nucleoli. Parental AR4-2J cells treated with exogenous FGF
      2 exhibited identical localizations, suggesting that in A5 cells the 18 kDa form
      followed the same translocation pathways than the exogenous FGF-2. By contrast,
      in A3 cells the 22.5 kDa form was predominantly localized in the nucleoplasm but
      was undetectable on the cell surface, suggesting its direct translocation to the
      nucleus. Northern and Western blot analysis showed that cells expressing the high
      molecular weight form exhibited a decrease of laminin B1 protein level and mRNA
      stability. In contrast, collagen IV and fibronectin expressions were unmodified
      either in FGF-2-transfected cells or in parental cells treated by exogenous FGF
      2. Thus, these data indicate that: 1) 18 and 22.5 kDa FGF-2 are preferentially
      localized in different nuclear compartments and 2) the high molecular weight form
      plays a role on the expression of some ECM components.

PMID- 8741214
TI  - Retinoic acid-induced RB (retinoblastoma) hypophosphorylation enhanced by CGP
      52411 (4,5-dianilinophthalimide), an EGF family tyrosine kinase receptor
      inhibitor.
AB  - Retinoic acid is a known morphogen which can regulate cell proliferation and
      differentiation and also induces the hypophosphorylation of the RB
      (retinoblastoma tumor suppressor gene) protein, a known cell cycle regulatory
      protein. The mechanism by which these processes occur is unclear. We find that
      these processes can be regulated by CGP 52411, 4,5-dianilinophthalimide, an
      inhibitor of tyrosine protein kinases of the EGF receptor subfamily. Retinoic
      acid causes the largely phosphorylated RB protein expressed in proliferating HL
      60 human promyelocytic leukemia cells to shift to the unphosphorylated form, as
      well as causing the cells to G0 arrest and differentiate. Addition of CGP 52411
      accelerated the redistribution of the RB protein expressed in HL-60 cells to the
      unphosphorylated form, enhancing the effects of the retinoic acid. By itself CGP
      52411 had no apparent effect on the RB protein expressed in HL-60 cells. CGP
      52411 also accelerated the retinoic acid-induced accumulation of cells in G1/0
      and the phenotypic conversion of cells to the mature myeloid phenotype,
      suggesting that its target is common to the regulation of both RB phosphorylation
      and cell proliferation and differentiation. CGP 52411 had a similar effect on the
      RB phosphorylation shift induced by 1,25-dihydroxy vitamin D3, a ligand for a
      receptor in the same steroid thyroid hormone superfamily as retinoic acid.
      Increasing the concentration of CGP 52411 enhanced the acceleration of RB
      hypophosphorylation in the case of both retinoic acid and 1,25-dihydroxy vitamin
      D3. The data are consistent with the negative regulation of retinoic acid induced
      RB protein dephosphorylation coupled to cell cycle arrest and differentiation by
      a receptor tyrosine kinase sensitive to CGP 52411.

PMID- 8741215
TI  - Kinetic analysis of epidermal growth factor endocytosis in rat hepatocytes.
      Effects of diabetes.
AB  - In the present study we followed the different steps of epidermal growth factor
      receptor (EGF-R) endocytosis in freshly isolated rat hepatocytes. Hepatocytes
      exhibit two classes of surface EGF receptors consisting of approximately 5,000
      high-affinity sites (Kd = 15 pM) and 166,000 low-affinity sites (Kd = 670 pM).
      Binding of labeled EGF to hepatocytes permeabilized by digitonin shows that 75%
      of the total EGF-R are localized at the cell surface. At 37 degrees C,
      hepatocytes continuously internalized and degraded EGF in spite of a down
      regulation of cell surface receptors. The internalization rate constants measured
      as a function of a range 125I-EGF concentrations (0.01 - 5 nM) involving various
      degrees of EGF-R occupancy show superimposable curves. This indicates that the
      specific internalization rate of EGF-R complex is independent of receptor
      occupancy. Streptozotocin-induced diabetes reduces the number of low-affinity EGF
      R to 50,000 and produces a complete loss of high-affinity sites. The dynamics of
      125I-EGF endocytosis show that diabetic hepatocytes fail to down-regulate the
      surface EGF-R efficiently although the constant rate of internalization is not
      modified. Decreased down-regulation of EGF-R together with enhanced EGF
      endocytosis suggest a greater efficiency in EGF-R recycling in diabetic rat
      hepatocytes.

PMID- 8741216
TI  - Inhibition of the vacuolar H(+)-ATPase with bafilomycin reduces delivery of
      internalized molecules from mature multivesicular endosomes to lysosomes in HEp-2
      cells.
AB  - In the human carcinoma cell line HEp-2, endosomes are multivesicular bodies
      (MVBs) which gradually mature and eventually fuse with other mature endosomes
      and/or with preexisting lysosomes. Selective inhibition of the vacuolar H(+)
      ATPase with bafilomycin A1 (Baf) did not influence endocytic uptake and recycling
      of the protein toxin ricin. Moreover, quantification of immunogold labeling on
      ultracryosections revealed that the frequency by which MVBs containing
      internalized cationized gold (Cat.Au) also labeled for the cation-independent
      mannose-phosphate receptor (MPR) was the same with and without Baf, suggesting
      that formation and maturation of MVBs were unchanged in the presence of Baf.
      However, degradation of ricin was strongly reduced by bafilomycin, and this
      reduction was not only due to increased pH in lysosomes. Thus, quantitative
      lmmunogold labeling showed that the Baf-induced alkalinization reduced the
      transfer of internalized Cat.Au to lysosomes, as defined by their content of
      human lysosome-associated membrane protein 1 (h-lamp-1) and cathepsin D.
      Accordingly, although low vacuolar pH does not seem to be required for transport
      to MPR-containing endosomes, it seems to be important for a late fusion step
      along the endocytic pathway.

PMID- 8741218
TI  - Transfected parvalbumin alters calcium homeostasis in teratocarcinoma PCC7 cells.
AB  - Indirect evidence supports a protective role of some EF-hand calcium-binding
      proteins against calcium-induced neurotoxicity. Little is known about how these
      proteins influence cytosolic calcium levels. After cloning the parvalbumin cDNA
      into an expression vector, teratocarcinoma cells (PCC7) were transfected.
      Parvalbumin-transfected and mock-transfected cells were loaded with the calcium
      indicator fura-2 and were exposed, in the same dish, to different concentrations
      of the calcium ionophore A23187 or to KCI. The results show that parvalbumin
      transfected PCC7 cells had much better calcium buffering capacity than control
      cells.

PMID- 8741217
TI  - Expression of synaptosomal-associated protein SNAP-25 in endocrine anterior
      pituitary cells.
AB  - A growing body of evidence indicates that the fundamental molecular mechanism of
      exocytosis in the secretory pathway may be structurally similar in all eukaryotic
      cells. The synaptosomal-associated protein of 25 kDa (SNAP-25) is a plasma
      membrane protein involved in regulated exocytosis in neurons. In order to compare
      exocytotic components in neurons and endocrine cells, we have analyzed the
      expression of SNAP-25 in the rat anterior pituitary. Western blotting analysis
      documented the presence of SNAP-25 in anterior pituitary homogenates and cultured
      anterior pituitary cells. In addition to SNAP-25, other neuronal proteins
      involved in exocytosis (syntaxin, VAMP/synaptobrevin and Rab3A) were also
      detected in the anterior pituitary. The specific expression of SNAP-25 mRNA in
      anterior pituitary cells was also corroborated by Northern analysis. SNAP-25
      immunoreactivity was located at the plasma membrane of endocrine anterior
      pituitary cells. Characteristically, patches of fine punctate deposits exhibited
      intense SNAP-25 immunoreactivity. Double-labeling immunocytochemistry revealed
      that SNAP-25 was mainly associated with gonadotroph cell populations.
      Furthermore, we demonstrate that in the anterior pituitary, SNAP-25 is
      selectively cleaved by clostridial neurotoxins. In conclusion, our results
      establish the presence of SNAP-25 in secretory anterior pituitary cells and
      suggest a potential role of this protein in the secretion of adenohypophysial
      hormone.

PMID- 8741219
TI  - In vivo observation of large foreign DNA molecules in host plant cells.
AB  - We have developed a system to monitor microscopically the fate of foreign DNA
      within plant cells in vivo. Fluorescein-11-dUTP was used to label DNA during
      target-specific amplification by polymerase chain reaction (PCR). Labeled DNA
      fragments of 1.5-3.5 kb were prepared and then transported into tobacco
      protoplasts by polyethylene glycol (PEG)-mediated direct gene transfer. We
      localized the foreign, labeled DNA within the cell by confocal laser scanning
      microscopy.

PMID- 8741220
TI  - New in situ approaches to study the induction of pollen embryogenesis in Capsicum
      annuum L.
AB  - The induction of pollen embryogenesis in Capsicum annuum L. has been studied at
      the cellular level using various in situ approaches with several molecular probes
      for DNA, RNA and proteins. The late vacuolated microspore and the young
      bicellular pollen grain are stages of gametophytic development in which
      embryogenesis can be induced. Our results show that the late vacuolated
      microspore stage is most responsive to embryogenesis induction. The proliferating
      cell nuclear antigen (PCNA) has been immunolocalized at the electron microscopy
      level, in order to map replication sites in relation to the fine structure of
      chromatin. It shows different patterns of labelling at both developmental stages
      studied, revealing that the late vacuolated microspore is in a period of
      replication. Other in situ studies have been performed to characterize the state
      of nuclear activity at the specific developmental stages in which the embryogenic
      induction can occur. The modern in situ terminal-deoxy-nucleotidyl transferase
      (TdT) reaction for DNA, the immunolocalization of various nuclear antigens (as
      snRNPs, fibrillarin, RNA) and the ultrastructural in situ hybridization using 18S
      and 25S ribosomal probes provided valuable data bout the specific features
      displayed by the functional nuclear compartments of the microspore, and the young
      vegetative and generative cells. They are related not only to the state of gene
      activity but also with probably the ability to switch to the sporophytic pathway
      at specific developmental times of their gametophytic program.

PMID- 8741221
TI  - Retinoic acid-induced heparin binding (RIHB, chicken midkine) factor expression
      by cultured chondrocytes is strongly enhanced by ascorbic acid.

PMID- 8741222
TI  - Trigeminal motoneuron responses to vestibular stimulation in the guinea pig.
AB  - Experiments performed in the guinea pig were aimed at evaluating the effect of
      electric or caloric stimulations of the vestibular afferents on the electrical
      activity of the jaw-closing and jaw-opening trigeminal motoneurons. Results
      showed that masseter and digastric motoneurons mainly responded to vestibular
      ampullar activation with excitatory responses, with latencies being shorter for
      contralateral than ipsilateral ampullar stimulation. Differences in latencies
      between the jaw-closing and jaw-opening trigeminal motoneurons were observed: the
      masseter motoneurons constantly responded about 2 msec earlier than the digastric
      motoneurons. These results suggest that the vestibular-trigeminal relationship is
      quite complex and uses multiple systems to connect the vestibular apparatus with
      the trigeminal motor nuclei. From the functional point of view, the vestibular
      trigeminal relationship may play a role in the dynamic control of the jaw muscle
      tone during head movements.

PMID- 8741223
TI  - Nucleus basalis magnocellularis and pedunculopontine tegmental nucleus: control
      of the slow EEG waves in rats.
AB  - Certain human disorders, which are characterized by learning and memory
      disturbances, are also accompanied by synchronizations of the cortical
      electroencephalogram (EEG). Although the EEG synchronization was casually related
      to the degeneration of the cholinergic basal forebrain, degenerations were found
      also in the cholinergic pontomesencephalic tegmentum. The present study was
      carried out to prove whether lesions of rat's pedunculopontine tegmental nucleus
      (PPTg) may cause EEG synchronizations like lesions of the basal forebrain. The
      effects of the unilateral ibotenic acid lesions of the nucleus basalis
      magnocellularis (NBM) and of the PPTg on the frontal and occipital EEG were
      compared in different behavioural states. The NBM lesion caused unilateral
      spectral power increases of all frequencies up to 20 Hz in the frontal EEG that
      were stronger with increased arousal level. Additionally, synchronized spike and
      wave discharges appeared in the frontal EEG. The NBM may suppress especially the
      delta EEG waves in the frontal motor cortex during motor active behaviours. The
      PPTg lesion caused unilateral suppressions of the occipital theta rhythm during
      exploratoring sniffing. During grooming the power of the frontal delta waves were
      elevated. Furthermore, the PPTg lesion caused a suppression of slow sleep waves.
      The results may indicate that a degeneration of both brain regions may change
      differently the power of the cortical slow EEG waves.

PMID- 8741224
TI  - Receptive field asymmetries and sensitivity to random dot stereograms.
AB  - The differences between the two monocular receptive fields of cortical cells were
      measured and compared to their disparity tuning in the awake behaving monkey.
      Several receptive field properties (direction selectivity, orientation
      preference, eye preference and response modulation) were determined for each eye
      using sweeping bright bars. The disparity sensitivity of these cells was also
      assessed by plotting their response profile, determined for each cell under
      strictly binocular cyclopean stimulation (dynamic random dot stereograms, RDS).
      We have found that large differences between the two monocular receptive fields
      were infrequent and, apparently, not related with the disparity sensitivity
      profile. We conclude that the monocular asymmetries tested in this study and the
      sensitivity to positional binocular disparities present in RDS, might be linked
      to different mechanisms involved in depth perception in the visual system.

PMID- 8741225
TI  - Effect of ambient temperature on power spectral density of arterial pressure
      during sleep in the rat.
AB  - Power spectral density (PSD) of arterial pressure (AP) during sleep was observed
      at various ambient temperatures (Ta: 16, 22 and 28 degrees C). Average AP and
      heart rate (HR) during sleep increased with lowering of Ta. PSD of AP during slow
      wave sleep (SWS) decreased over the entire range of frequency with increasing of
      Ta. Low frequency component (approximately 0.1 Hz) in PSD of AP during
      paradoxical sleep (PS) increased, while higher frequency component (0.1 Hz
      approximately) decreased with increasing of Ta. This study suggests that Ta
      affects the PSD of AP during sleep, and that vasomotor sympathetic tone during PS
      might increase with increasing of Ta.

PMID- 8741227
TI  - Effects of ovariectomy upon performance of a maze learning paradigm in the adult
      female rat.
AB  - To determine what effect ovariectomy and the accompanying sudden loss of
      circulating gonadal hormones has on spatial learning performance in the adult
      rat, two groups of rats were tested on the Lashley III simple alley maze
      following surgery. Ovariectomized animals were compared with a control group of
      animals that underwent laparotomy at the same time. The ovariectomized group
      evidenced superior performance on the maze task, as measured by latency to reach
      goal (running times) and error scores. It is suggested that this finding provides
      further evidence for the role of gonadal steroid hormones in the manipulation of
      functions related to learning and memory, especially in the hippocampus.

PMID- 8741226
TI  - Polysynaptic pathways from high threshold muscle afferents innervating hindlimb
      muscles to tail motoneurons in the spinalized cat.
AB  - The postsynaptic potentials (PSPs) after stimulating hindlimb flexor (PBSt) and
      extensor muscle nerves (LGS) were recorded from 64 tail motoneurons innervating
      m. extensor caudae lateralis and m. flexor caudae longus in the spinalized cats.
      Postsynaptic potentials were produced after stimulating high threshold muscle
      afferent fibers (group II and group III) and the average central latencies of
      PSPs were distributed in a wide range between 4.5 and 15.1 ms. Opposite effects
      on tail motoneurons were observed between stimulation of flexor and extensor
      muscle nerves, or ipsilateral and contralateral muscle nerves.

PMID- 8741228
TI  - Rhythmic discharges recorded from tail muscle nerves after injection of nialamide
      and L-DOPA solution in spinalized cats.
AB  - In 22 decapitated and high spinalized cats, rhythmic discharges were recorded
      from the nerves supplying the tail muscles, m. extensor caudae lateralis (ECL)
      and m. flexor caudae longus (FCL) after intravenous injection of Nialamide and L
      DOPA solution. In 15 out of 22 cats, stable rhythmic discharges were recorded
      from tail muscle nerves. Two different discharge patterns were observed. The
      predominant pattern consisted of an alternating activation between left and right
      tail muscle nerves and a synchronous activation of ECL and FCL nerves on one
      side. The second pattern consisted of synchronous activity involving all four
      tail muscle nerves.

PMID- 8741229
TI  - The importance of dopamine D4 receptors in the action and development of
      antipsychotic agents.
AB  - The dopamine D4 receptor, recently identified by molecular biological techniques,
      is expressed in areas of the brain implicated in the pathophysiology of
      schizophrenia. Although it has a lower affinity than the D2 receptor for most
      antipsychotic drugs, the D4 receptor has a higher affinity for clozapine, which
      may explain the unique efficacy of clozapine in the treatment of schizophrenia.
      However, there is no association between genetic alterations of the D4 gene and
      either the development of schizophrenia or response to clozapine administration,
      nor is the absence of the receptor related to major neuropsychiatric deficits.
      The report of an increase in D4 receptor density in the striatum in schizophrenia
      has not been consistently confirmed. Thus, it appears that there is little to
      support the development of D4 antagonists as potential antipsychotic agents.

PMID- 8741231
TI  - Amyotrophic lateral sclerosis: current and future treatment strategies.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal, enigmatic disorder characterised
      by relentless progression of muscle wasting and weakness until death ensues due
      to respiratory muscle failure. Intellectual functions are usually spared. ALS,
      known also as motor neuron disease (MND) in the UK, maladie de Charcot in France
      and Lou Gehrig's disease in the US, is usually sporadic, but between 5 and 10% of
      all cases are hereditary, usually inherited as autosomal dominant. Previously
      thought to be untreatable, as well as incurable, just in the last 3 years ALS has
      been the greatest clinical application of recent exciting break-throughs in
      preclinical neurobiology research. Although definitive information regarding the
      cause(s) and pathogenesis of ALS still escapes us, meaningful demonstration of
      intercession in the downhill course with specific therapy has been suggested,
      giving reason to be hopeful, if cautiously and critically optimistic. This review
      focuses on the recent work from the fields of growth/trophic factors,
      glutamate/neurotoxicity, neuroprotection and proteases and inhibitors, as well as
      the approaches to measuring specific effects in patients with the illness. It
      ends with a eye to the horizon, and the future, and where ALS treatment
      strategies may be heading after the millennium.

PMID- 8741230
TI  - The clinical potential of endothelin receptor antagonists in cardiovascular
      medicine.
AB  - The endothelin family of peptides are extremely potent endogenous vasoconstrictor
      and pressor agents. Of the 3 isoforms, endothelin-1 is the major isoform produced
      by the vascular endothelium and is, therefore, likely to be of most importance
      for regulation of vascular function. Two endothelin receptor subtypes have so far
      been cloned in mammalian species; ET A, and ET B. Both receptor subtypes are
      found on smooth muscle cells and mediate the vasoconstrictor and pressor actions
      of endothelin. The ET B receptor is also found on vascular endothelial cells and
      mediates endothelin-dependent vasodilatation through release of nitric oxide and
      prostacyclin. Since their discovery in 1988, the endothelins have been the
      subject of intense research on their physiological function and potential
      pathophysiological role in cardiovascular disease. There is now good evidence
      that endothelin regulates vascular tone and blood pressure, and studies to
      support the development of endothelin receptor antagonists in conditions
      associated with chronic vasoconstriction, such as hypertension and heart failure,
      as well as in vasospastic disorders, such as subarachnoid haemorrhage and
      Raynaud's disease. There are now a number of selective ET A and combined ET A/B
      receptor antagonists available for preclinical studies. However, it is still not
      clear which of these will prove to be of most therapeutic value. Some of these
      agents are currently being assessed in early phase clinical trials. Endothelin
      receptor antagonists represent a novel therapeutic approach to a fundamental and
      newly discovered endogenous vasoconstrictor mechanism. The results of the current
      clinical trials are awaited with considerable interest.

PMID- 8741233
TI  - Head and neck cancer: guidelines for chemotherapy.
AB  - Head and neck cancer is estimated to be one of the most prevalent cancers in the
      world. This tumour type accounts for 5% of all new cancer cases in the US and
      Europe each year. Patients with locally recurrent or metastatic squamous cell
      carcinoma of the head and neck have a poor prognosis, with a median duration of
      survival between 4 and 6 months. During the past few years, screening for
      potentially active new compounds, new associations and new modalities of
      chemotherapy administration have had some degree of success. Clinical
      investigations have also focused on the addition of chemotherapy to locoregional
      treatment for patients with locally advanced disease. Induction chemotherapy or
      concomitant chemo- and radiation therapy can result in high response rates, and
      reduced incidence of distant metastases. However, there is no clear demonstration
      of any benefit from the addition of chemotherapy to locoregional therapy on
      overall survival in patients with resectable disease. In patients with resectable
      laryngeal or hypopharyngeal cancer, chemotherapy combined with radiotherapy can
      be considered as a standard treatment option for larynx preservation, keeping
      total laryngectomy reserved for salvage therapy. In patients with unresectable
      head and neck cancer, simultaneous chemoradiotherapy has been shown to improve
      locoregional control and survival, at the cost of greater toxicity. Outside
      clinical trials, this approach can also be considered as a standard therapy for
      unresectable disease.

PMID- 8741234
TI  - Current guidelines for the treatment of congestive heart failure.
AB  - Overt congestive heart failure (CHF) has a prevalence of 1% of the population.
      The predominant symptoms of patients with CHF are fatigue and dyspnoea. Fatigue
      is thought to result from changes in peripheral muscle metabolism secondary to
      decrease vasodilative capacity and physical inactivity. An increase of peripheral
      perfusion by vasodilator therapy and physical activity are therefore recommended.
      Beside overt decompensation, where dyspnoea results from acute pulmonary
      congestion due to backward failure, increased physiological dead space
      ventilation caused by pulmonary ventilation/perfusion mismatch accounts, to a
      large degree, for dyspnoea, and can be improved by vasodilator therapy. According
      to the pathophysiology of CHF, normalisation of loading conditions and myocardial
      inotropy are the parameters addressed by various pharmacological agents in order
      to alleviate symptoms and slow progression of the disease. Diuretics are rapidly
      acting and effective agents to improve congestion and decrease filling pressures.
      Digitalis improves haemodynamics and symptomatology by increasing inotropy and
      slowing resting heart rate in atrial fibrillation; however, prognostic effects
      have yet to be proved. The introduction of vasodilators has significantly
      improved the prognosis of the disease, and the administration of ACE inhibitors
      in particular has been shown to slow progression of CHF. This results in a
      substantial decrease in morbidity and mortality. The present article appraises
      the role of the currently used drugs in the treatment of CHF, considering effects
      on pathophysiology and clinical outcome and provides an approach to a
      differential drug regimen.

PMID- 8741232
TI  - Emerging drug treatments for solid tumours.
AB  - A number of novel anticancer agents have emerged during the past few decades,
      which show high activity in preclinical tumour models and promising activity in
      early trials in patients with solid tumours. Most of the agents have novel and
      unique mechanisms of action, and show activity against a variety of malignancies,
      including tumours which are notoriously resistant to systemic treatment.
      Recently, our understanding of the molecular basis of cancer has increased
      considerably. This is reflected in the development of agents that are directed at
      well defined molecular targets, such as the mitotic tubulin/microtubuli system
      (taxoids), nuclear enzymes (topoisomerase I inhibitors) and cell signal
      transduction pathways (protein kinase C inhibitors). In addition, significant
      advances have been made in our understanding of mechanisms of toxicity,
      especially of cisplatin. This has resulted in the development of agents
      modulating cisplatin toxicity, among which amifostine (WR-2721) is one of the
      most promising. The outlined emerging drug therapies with novel anticancer agents
      and treatment modalities will, it is hoped, result in increased response rates of
      advanced tumours, longer disease-free and total survival and better palliative
      care.

PMID- 8741238
TI  - Inflammation as an early component of atherosclerosis and vascular damage--a role
      for P-selectin and platelet-activating factor.

PMID- 8741237
TI  - Clarithromycin and omeprazole as helicobacter pylori eradication therapy in
      patients with H. pylori-associated gastric disorders.
AB  - Helicobacter pylori is susceptible to many antibacterial drugs in vitro but has
      proved difficult to eradicate in vivo. The macrolide clarithromycin has good
      activity against H. pylori in vitro and has demonstrated the highest eradication
      rate for any antibacterial monotherapy in vivo. However, it is clear that
      antibacterial monotherapy is not a sufficiently effective treatment for patients
      with H. pylori infection. The suggestion that high intragastric acidity impairs
      the action of antibacterial drugs led to the evaluation of combination H. pylori
      eradication regimens including H+,K+-ATPase inhibitors and antibacterial drug(s)
      with or without bismuth compounds. Noncomparative studies evaluating the efficacy
      of dual therapy with clarithromycin plus omeprazole in patients with H. pylori
      infection have reported eradication rates of between 58 and 83% > or = 4-weeks
      after therapy. In comparative studies, clarithromycin plus omeprazole was at
      least as effective as amoxicillin plus omeprazole. However, direct comparisons
      have shown that eradication rates achieved by dual therapy are not as high as
      those achieved by triple therapy. Indeed, triple therapy with clarithromycin plus
      omeprazole in combination with amoxicillin or a nitroimidazole has achieved
      eradication rates of up to 100%. Although 14-day triple drug regimes were
      initially considered necessary for effective eradication, it now seems clear that
      7-day regimes are equally effective. Factors known to influence response to H.
      pylori eradication therapy include bacterial resistance and patient compliance. A
      review of 4 studies evaluating the efficacy of dual eradication therapy with
      clarithromycin plus omeprazole reported an overall incidence of adverse events
      (patient or investigator reported, whether related to treatment or not) of 45%.
      The most common adverse event was taste disturbance (an adverse event commonly
      reported during the development of clarithromycin); nausea, headache, diarrhoea,
      vomiting and abdominal pain occurred less frequently. Although dual therapy might
      be expected to cause fewer adverse events than triple therapy this has not been
      the case in direct comparisons conducted to date. Thus, although clarithromycin
      plus omeprazole is associated with an H. pylori eradication rate of approximately
      70%, 1 week of triple therapy with these 2 drugs together with amoxicillin or a
      nitroimidazole, which eradicates the organism in approximately 90% of cases, may
      represent optimal H. pylori eradication therapy.

PMID- 8741239
TI  - Comparison of aortic valve replacement and percutaneous aortic balloon
      valvuloplasty for elderly patients with aortic stenosis.
AB  - The outcome of aortic balloon valvuloplasty (ABV) was compared with that of
      aortic valve replacement (AVR) in aortic stenosis (AS) patients more than 60
      years old. The indications for ABV included low respiratory and renal function,
      cancer, the patient's refusal of surgery, and low daily activity. Twenty six
      patients underwent AVR and 13 underwent ABV. Initially, the AVR group was younger
      and more symptomatic than the ABV group. Two perioperative deaths occurred in the
      AVR group, while there were none in the ABV group. Twenty-four AVR patients and
      12 ABV patients had a successful outcome, with remarkable pressure gradient
      reduction in both groups. In the follow-up, only 1 death and no cardiac events
      were detected in the AVR group (mean follow-up of 27 months), whereas 3 deaths, 6
      heart failures, 2 repeated ABV, and 4 AVR were seen in the ABV group (mean follow
      up of 10 months). The data showed that ABV was safer than AVR, but a higher rate
      of restenosis limited its efficacy. In the ABV group, a higher ratio of balloon
      size to aortic diameter correlated with longer event-free survival. We concluded
      that for elderly AS patients, ABV should be used only in those with high surgical
      risk as a palliative therapy or a bridge therapy to AVR, and AVR should be
      primarily recommended under rigid evaluation of the patient's physical status.

PMID- 8741241
TI  - Caffeine induces ventricular tachyarrhythmias possibly due to triggered activity
      in rabbits in vivo.
AB  - Caffeine induces delayed afterdepolarizations (DADs) and triggered activity in
      isolated cardiac tissue. We investigated the ability of caffeine to induce
      triggered ventricular arrhythmias in rabbits in vivo. During continuous infusion
      of caffeine at doses of 0.3 or 1.0 mg/kg per min, ventricular pacing was
      performed with 50 stimuli with a cycle length of 220 msec (basic pacing train)
      every 5 min until ventricular tachycardia (VT) was induced. The effects of
      programmed stimulation and pharmacologic agents on the induction of ventricular
      ectopic beats (VEBs) were examined. Pacing protocols were carried out in the
      presence of vagal-induced slowing of sinus rhythm. VT was induced by a basic
      pacing train during the infusion of caffeine at 1.0 mg/kg per min, but not at 0.3
      mg/kg per min. An increase in the pacing rate or the number of stimuli resulted
      in 1) a decrease in the first postpacing interval, and 2) an increase in the
      number of postpacing VEBs. Induction of VT was suppressed by intravenous bolus
      injections of verapamil, propranolol and adenosine. At the time of the initial
      induction of VT, the plasma concentration of caffeine was 87 +/- 2 micrograms/ml
      and the plasma level of norepinephrine increased from 666 +/- 166 pg/ml at
      baseline to 1121 +/- 245 pg/ml. These results suggest that catecholamine
      associated triggered activity may be responsible for caffeine-induced VT.

PMID- 8741240
TI  - Relationship between intracoronary thrombolysis and fibrino-coagulation--special
      reference to TAT/PIC and FPA/PIC.
AB  - To clarify the relationship between the results of intracoronary thrombolytic
      therapy (ICT) and fibrino-coagulation in patients with acute myocardial
      infarction (AMI), the thrombin-antithrombin III complex (TAT) and fibrinopeptide
      A (FPA), as indices of accelerated coagulation, and the plasmin- alpha 2-plasmin
      inhibitor complex (PIC), as an index of accelerated fibrinolysis in peripheral
      blood, were measured just before and after heparin injection (5,000 U), and
      immediately after ICT. Twenty-four patients with AMI were divided into 2 groups
      according to the results of ICT; successful ICT (group S) and unsuccessful ICT
      (group F). As a control group (group C), 14 age-matched normal volunteers were
      also studied. The levels of TAT and FPA before ICT were significantly higher in
      groups S and F than in group C (p < 0.01). The TAT level before ICT in group F
      was higher than that in group S (p = 0.07), however, the TAT, FPA and PIC levels
      showed no significant differences between groups S and F at each sampling time.
      TAT/PIC before ICT was significantly higher in group F than in group S (F: 0.026
      +/- 0.020 vs S: 0.008 +/- 0.004, p < 0.05), whereas there was no remarkable
      difference in FPA/PIC between groups S and F. These results indicate that hyper
      coagulation had occurred in the AMI cases and that coagulation had been more
      accelerated in group F. TAT/PIC might be an index of the equilibrium of the
      fibrino-coagulating system. Therefore, TAT/PIC measurement before thrombolytic
      therapy may be more useful than TAT measurement alone for evaluating
      recanalization in ICT.

PMID- 8741242
TI  - A case report of angioedema during long-term (66 months) angiotensin converting
      enzyme inhibition therapy with enalapril.
AB  - We describe a rare case of ACE inhibitor-induced angioedema during long-term
      therapy in a 51-year-old male patient with essential hypertension; and this is
      the third case reported of this adverse reaction in Japan. The patient received
      enalapril for 66 months, and complained of a dry cough which was mild and
      tolerable. Recently, he noted tenderness of his mouth, face, swelling of lips and
      tongue for 3 to 4 h after taking his morning dose of enalapril. These symptoms
      abated spontaneously, so he continued taking the drugs. He again noted similar
      episodes of angioedema 29 days after the first experience. He had no further
      episodes of angioedema or dry cough after cessation of enalapril. This case of
      angioedema developed during long-term therapy with enalapril administered as
      19,930 mg of enalapril maleate. We emphasize that angioedema may occur at any
      time during the use of enalapril.

PMID- 8741235
TI  - Imipenem/cilastatin: an update of its antibacterial activity, pharmacokinetics
      and therapeutic efficacy in the treatment of serious infections.
AB  - The prototype carbapenem antibacterial agent imipenem has a very broad spectrum
      of antibacterial activity, encompassing most Gram-negative and Gram-positive
      aerobes and anaerobes, including most beta-lactamase-producing species. It is
      coadministered with a renal dehydropeptidase inhibitor, cilastatin, in order to
      prevent its renal metabolism in clinical use. Extensive clinical experience
      gained with imipenem/cilastatin has shown it to provide effective monotherapy for
      septicaemia, neutropenic fever, and intra-abdominal, lower respiratory tract,
      genitourinary, gynaecological, skin and soft tissues, and bone and joint
      infections. In these indications, imipenem/cilastatin generally exhibits similar
      efficacy to broad-spectrum cephalosporins and other carbapenems and is at least
      equivalent to standard aminoglycoside-based and other combination regimens.
      Imipenem/cilastatin is generally well tolerated by adults and children, with
      local injection site events, gastrointestinal disturbances and dermatological
      reactions being the most common adverse events. Seizures have also been reported,
      occurring mostly in patients with impaired renal function or CNS pathology, or
      with excessive dosage. Although it is no longer a unique compound, as newer
      carbapenems such as meropenem are becoming available, imipenem/cilastatin
      nevertheless remains an important agent with established efficacy as monotherapy
      for moderate to severe bacterial infections. Its particular niche is in treating
      infections known or suspected to be caused by multiresistant pathogens.

PMID- 8741236
TI  - Enoxacin: a reappraisal of its clinical efficacy in the treatment of
      genitourinary tract infections.
AB  - Enoxacin is a 6-fluoronaphthyridinone antibacterial agent with good in vitro
      activity against Neisseria gonorrhoeae and most Gram-negative urinary tract
      pathogens. It is less active in vitro against Acinetobacter spp., Pseudomonas
      aeruginosa, and most Gram-positive bacteria, than against Gram-negative
      organisms. Enoxacin is rapidly absorbed, with a high oral bioavailability (87 to
      91%). Of the absorbed dose, 44 to 56% is excreted unchanged in the urine, with
      peak urinary concentrations (>500 mg/L within 4 hours) remaining high (>100 mg/L)
      for up to 24 hours, sufficient to inhibit most urinary tract pathogens. Single
      (400 mg) and multiple oral dose regimens (100 to 600 mg twice or 3 times daily
      for 5 to 14 days) of enoxacin are as effective for the treatment of patients with
      complicated or uncomplicated urinary tract infections as other antibacterial
      agents such as amoxicillin, cefuroxime axetil, cotrimoxazole (trimethoprim
      sulfamethoxazole) or trimethoprim. Noncomparative data suggest that enoxacin is
      also an effective agent for the treatment of prostatitis. Single 400 mgoral doses
      of enoxacin produce >/- 95% bacteriological cure rates in gonococcal infections,
      comparable to those produced by single intramuscular doses of ceftriaxone 250 mg.
      Perioperative doses of oral enoxacin 200 mg provide effective prophylaxis against
      postoperative bacteriuria after transurethral resection of the prostate.
      Concomitant administration of enoxacin with a number of commonly used therapeutic
      agents (e.g. antacids, methylxanthines, warfarin) affects the pharmacokinetic
      properties of either enoxacin or the coadministered agents. Enoxacin is
      reasonably well tolerated, with the incidence of adverse experiences ranging from
      0 to 24%. Adverse events are mainly gastrointestinal, neurological or
      dermatological and resolve with minimal intervention. Overall, although enoxacin
      exhibits a number of clinical characteristics that are similar to those of other
      agents for the treatment of genitourinary tract infections, the advantages
      offered by this agent generally do not outweigh those of alternative
      fluoroquinolone agents. Thus, it is likely to prove to be yet another addition to
      the list of agents available for the management of these infections.

PMID- 8741243
TI  - A case report of simultaneous surgery for Wolff-Parkinson-White syndrome combined
      with hemolytic anemia and mitral stenosis.
AB  - A 46-year-old woman with mitral stenosis, WPW syndrome, hemolytic anemia due to
      spherocytosis, and hypothyroidism with Hashimoto's thyroiditis, was admitted with
      palpitations and dyspnea due to paroxysmal atrial fibrillation with a rapid
      ventricular response, and was treated by electrical cardioversion. We selected
      surgical intervention to treat the mitral stenosis and WPW syndrome, as some
      tachycardia episodes due to atrial fibrillation have resulted in repeated
      congestive heart failure. In 1983 we simultaneously performed a division of the
      posteroseptal accessory pathway and a mitral valve replacement with a
      bioprosthetic valve under cardiopulmonary bypass, using a membrane oxygenator
      after splenectomy to compensate for the hemolytic anemia due to spherocytosis.
      Her postoperative course was favorable and she is now in good health with no
      episodes of tachycardia, congestive heart failure nor anemia occurring during the
      10 years that have followed the operation. Simultaneous surgery for WPW syndrome
      combined with other cardiac abnormalities and hematologic disorders achieved
      acceptable results in this case.

PMID- 8741244
TI  - Pericardiectomy and coronary artery bypass grafting for constrictive pericarditis
      after heart surgery.
AB  - A 63-year-old male was operated on for chronic heart failure due to myocardial
      ischemia and constrictive pericarditis after heart surgery. He was in New York
      Heart Association (NYHA) class III under a large dose of diuretics. He underwent
      a pericardiectomy and coronary bypass surgery without cardiopulmonary bypass. His
      cardiac function improved with a patent graft. He is now, 1 year after surgery,
      in NYHA class I under a tapering dose of diuretics.

PMID- 8741245
TI  - Trans-systolic murmur during the Valsalva maneuver in a patient with apical
      aneurysm--a case report.
AB  - We present a 74-year-old female in whom a systolic murmur became trans-systolic
      during the Valsalva maneuver. The patient had had stable effort angina for 20
      years and coronary angiography revealed complete obstruction of the left anterior
      descending artery in addition to other atherosclerotic lesions. Left
      ventriculography showed a small apical aneurysm with a narrow orifice. Aorto
      coronary bypass surgery and aneurysmectomy were performed; true aneurysm was
      confirmed pathologically. We conclude that apical aneurysm with a narrow orifice
      can produce trans-systolic murmur.

PMID- 8741246
TI  - Vasospastic angina after chemotherapy by with carboplatin and etoposide in a
      patient with lung cancer.
AB  - We report here a case of vasospastic angina following the administration of
      Carboplatin (CBDCA) and Etoposide (VP-16) in a patient with small cell lung
      carcinoma. Although these drugs are commonly used to treat small cell lung
      carcinoma, there has been no previous report of vasospastic angina in a patient
      without a history of heart disease. Therefore, we should be aware of the
      possibility that vasospastic angina may develop even in a patient without any
      history of heart disease. While calcium antagonist and isosorbide dinitrate are
      generally helpful for preventing vasospastic angina, these drugs could not
      completely suppress vasospastic angina in this case.

PMID- 8741247
TI  - QRS alteration-induced torsade de pointes in a patient with an artificial
      pacemaker and hypokalemia.
AB  - The present patient demonstrated torsade de pointes (TdP) after a pacemaker
      implantation without a decrease in heart rate or pacemaker malfunction. Marked QT
      prolongation and TdP were closely related to alteration of the depolarization
      pattern (appearance of junctional rhythm). Resetting the pacemaker to a rate that
      inhibited spontaneous rhythm was effective in preventing TdP.

PMID- 8741249
TI  - Trigeminocerebellar artery--anatomy and possible clinical significance.
AB  - The trigeminocerebellar artery was found on the left side in one of 22
      brainstems, with the vasculature injected with India ink or methylmethacrylate.
      The trigeminocerebellar artery, which measured 910 microns in diameter, arose
      from the basilar artery. The artery was divided into the pontine, trigeminal,
      cerebellopontine, and cerebellar segments. The artery supplied the anterolateral
      and lateral part of the pons, the trigeminal nerve root, the middle cerebellar
      peduncle, and most of the petrosal surface of the cerebellar hemisphere. Although
      relatively rare, the trigeminocerebellar artery may cause trigeminal neuralgia.
      Occlusion of this artery would cause a syndrome similar to the lateral midpontine
      syndrome. The trigeminocerebellar artery could be misinterpreted on angiograms as
      the anterior inferior cerebellar artery with a high origin from the basilar
      artery.

PMID- 8741248
TI  - Dural invasion and proliferative potential of pituitary adenomas.
AB  - The relationship between invasiveness and proliferative potential was studied in
      31 cases of pituitary adenomas. The invasiveness was determined by histological
      examination of sellar floor dura resected during transsphenoidal surgery. The
      proliferative potential of adenoma specimens was examined immunohistochemically
      using monoclonal antibody (MIB-1). There were 11 adenomas with histologically
      verified dural invasion out of 31 cases. These adenomas had a higher MIB-1-
      positive ratio than adenomas without dural invasion (p < 0.05). Pituitary
      adenomas with a high proliferative potential tend to be invasive.

PMID- 8741250
TI  - Immunohistochemical study of medulloblastoma with a monoclonal antibody against
      human copper and zinc-superoxide dismutase.
AB  - Superoxide dismutase (SOD) expression in tumor tissues was investigated in 10
      cases of medulloblastoma by immunohistochemistry, using a monoclonal antibody
      against human copper and zinc-superoxide dismutase. Abundant SOD was expressed in
      tumors from patients with poor outcomes and little SOD in patients with good
      outcomes. These results suggest that resistance to adjuvant therapy depends on
      the amount of SOD in tumor tissues. The effects of adjuvant therapies for
      medulloblastomas depend on the production of free oxygen radicals, so if tumor
      cells contain a free radical scavenger such as SOD, the effects of adjuvant
      therapy may be reduced. Measurement of SOD in tumor tissues may be useful as a
      prognostic indicator for medulloblastoma.

PMID- 8741251
TI  - Transient alpha coma following minor head trauma in a patient with primitive
      trigeminal artery.
AB  - A 26-year-old male presented with transient alpha coma following minor head
      trauma after a traffic accident. His consciousness disturbance suddenly recovered
      3.5 hours later. He had not suffered cardiac arrest before admission, nor was
      taking any drugs. Magnetic resonance (MR) angiography 6.5 hours after
      consciousness recovery disclosed persistent primitive trigeminal artery (PTA)
      with minor segmental narrowings. Three months later, MR angiography revealed that
      both the PTA and the distal basilar artery were slightly diated without evidence
      of narrowing. Conventional angiography and single photon emission computed
      tomography revealed that the distal basilar artery was supplied mainly by the
      PTA. Transient circulatory disturbance due to traumatic angiospasm of the PTA may
      have caused hypoperfusion of the upper brainstem in this patient.

PMID- 8741252
TI  - Anomalous internal carotid artery-anterior cerebral artery anastomosis associated
      with fenestration and cerebral aneurysm.
AB  - A 69-year-old female presented with a ruptured aneurysm at the distal tip of a
      fenestrated anomalous artery which originated in the ophthalmic segment of the
      internal carotid artery (ICA), passed between the optic nerves, ascended along
      the midline, and formed the fenestration before dividing into the bilateral
      pericallosal arteries. The anomalous artery manifested as subarachnoid
      hemorrhage. Four days later, she died from severe pulmonary edema. The
      angiographic finding was confirmed by postmortem examination. Numerous
      perforating vessels from the anomalous artery and the distal ICA supplied the
      optic nerves and chiasm. This finding supports the idea that this anomalous
      vessel may be an extreme developmental variation of the prechiasmal arterial
      plexus.

PMID- 8741253
TI  - Hemorrhagic pituitary adenoma manifesting as transient global amnesia.
AB  - A 68-year-old female presented with recurrent transient global amnesia due to
      hemorrhagic prolactin-producing pituitary adenoma. Magnetic resonance imaging
      clearly revealed the anatomical relationship between the hematoma, within the
      parasellar tumor, and the compressed medial temporal lobe of the right (non
      dominant) hemisphere. Within 4 weeks after the start of bromocriptin
      administration, the adenoma had markedly regressed and the affected temporal lobe
      was decompressed. She has experienced no further episode of transient global
      amnesia. Magnetic resonance imaging is recommended to detect latent organic
      lesions responsible for transient global amnesia, although the disorder is
      considered to be benign and of functional origin.

PMID- 8741254
TI  - Suprasellar granular cell tumor.
AB  - A 75-year-old female presented with a suprasellar granular cell tumor. Computed
      tomography (CT) revealed a high dense suprasellar mass with strong postcontrast
      enhancement. Magnetic resonance imaging showed a round suprasellar mass, which
      was hyperintense on the T1-weighted images with nonhomogeneous enhancement after
      the administration of gadolinium-diethylenetriaminepenta- acetic acid, and
      hypointense on the T2-weighted images. Cerebral angiography demonstrated no
      abnormal findings. The tumor was partially removed via a right frontotemporal
      craniotomy. The histological diagnosis was suprasellar granular cell tumor. Her
      postoperative course was uneventful other than mild and transient diabetes
      insipidus. She has remained asymptomatic without CT evidence of tumor regrowth
      for 20 months after the surgery. Immunohistochemical studies showed positive
      reaction for S-100 protein in the tumor cell nuclei, but no reaction for glial
      fibrillary acidic protein, neurofilament protein, Leu-7, oxytocin, beta
      endorphin, adrenocorticotropic hormone, and vimentin. This case provides
      additional evidence for the astrocytic origin of suprasellar granular cell tumor.

PMID- 8741255
TI  - Radiosurgery for acoustic neurinoma with rapid growth and relatively high
      staining indexes for proliferating cell nuclear antigen and MIB-1.
AB  - A 54-year-old female presented with a rapidly growing acoustic neurinoma. The
      tumor doubling time was 216 days or less before surgery and staining indexes for
      proliferating cell nuclear antigen (PCNA) and MIB-1 were relatively high (4.1%
      and 2.1%, respectively). The tumor was partially removed, but regrowth was
      detected with a tumor doubling time of 205 days. She underwent gamma knife
      radiosurgery for the residual tumor. The periphery of the tumor was irradiated
      with a dose of 15 Gy. Magnetic resonance imaging 30 months later demonstrated
      significant tumor shrinkage. The tumor half time following irradiation was
      determined to be 401 days. Neither surgery nor radiosurgery produced any
      additional neurological deficit or complications. Gamma knife radiosurgery can
      control neurinoma growth even when the tumor shows rapid growth and a relatively
      high growth fraction indicated by high staining indexes for PCNA or MIB-1.

PMID- 8741256
TI  - Malignant fibrous histiocytoma of the lateral wall of the orbit.
AB  - A 58-year-old male presented with malignant fibrous histiocytoma originating from
      the lateral wall of the orbit, manifesting as left exophthalmos and diplopia on
      left lateral gaze. Magnetic resonance (MR) imaging demonstrated the tumor
      extending into the left orbit and under the temporalis muscle. The tumor was
      isointense with muscle on T1-weighted MR images and was surrounded by a low
      intensity rim, which was proved to be the capsule after histological examination.
      The tumor was completely removed after detaching the lateral orbital rim and
      zygomatic arch using the dismasking flap method. He underwent one course of
      CYVADIC chemotherapy and has demonstrated no recurrence for 1 year and 6 months
      postoperatively.

PMID- 8741257
TI  - Epithelial cyst in the cerebellopontine angle.
AB  - A 63-year-old male presented with a rare epithelial cyst in the left
      cerebellopontine angle manifesting as left facial nerve paresis and left
      cerebellar signs. Computed tomography revealed a well-defined cystic mass of
      homogeneous low density with no enhancement. Magnetic resonance imaging also
      demonstrated a cystic mass appearing as low intensity on T1-weighted images and
      high intensity on T2-weighted images. The cyst content was clear fluid. The cyst
      wall consisted of nonciliated, columnar epithelial cells, showing a
      pseudostratified arrangement in focal areas. Positive staining by periodic acid
      Schiff, Alcian blue, and carcinoembryonic antigen suggested that the cyst was an
      enterogenous cyst of endodermal origin. Cysts in this location often cause
      cranial nerve impairment, but the symptoms are usually resolved by surgical
      treatment.

PMID- 8741258
TI  - Factors affecting induction of neurological disorders in mice by paralysis
      inducing Friend-related PVC viruses.
AB  - Our previous studies showed that the passage of the Friend virus complex through
      rats generated variant MuLVs, designated PVC111, PVC211, PVC321 and PVC441, that
      induced neurological disorders associated with tremor and paralysis. In this
      study, we tested the pathogenicity of four different PVC viruses in mice.
      Although histopathological studies revealed spongiform degeneration in the spinal
      cords of NFS mice infected with each PVC virus, only PVC441 frequently induced
      tremor and paralysis. After a long latency, all of these viruses induced leukemia
      associated with severe anemia. Further studies with PVC441 revealed dose- and age
      dependence for tremor induction. In contrast to NFS mice, BALB/c, DBA/2 and
      C57BL/6 mice infected with PVC441 virus showed no neurological symptoms, although
      the virus could be isolated from the tissues of central nervous system. Despite
      the absence of neurological symptoms, a high degree of neuronal degeneration in
      the lumbar spinal cord was found in PVC441-infected BALB/c mice. A low degree of
      neuronal degeneration was found in PVC441-infected DBA/2 or C57BL/6 mice. Genetic
      crosses of these resistant mice with susceptible NFS mice indicated that
      resistance to tremor induction by PVC441 was dominant in all mouse strains and
      suggested that various host genes may control the susceptibility of mice to
      tremor induction by PVC441 virus.

PMID- 8741259
TI  - Contrast-enhanced MRI with gadodiamide injection in rat disease models.
AB  - The present study was designed to confirm the usefulness of contrast-enhanced
      magnetic resonance imaging (MRI) in diagnosing strokes of stroke-prone
      spontaneously hypertensive rats (SHRSP) and middle cerebral artery (MCA)
      occlusion, hepatocellular carcinoma and hydronephrosis of each experimental rat
      model. Male Sprague-Dawley rats (250-500 g), male SHRSP (ca. 250 g) and male F344
      rats (ca. 300 g) were used for the investigation. Gadodiamide injection
      (Omniscan, Daiichi Pharmaceutical Co., Ltd. and Nycomed AS, Norway) was
      administered intravenously as the contrast agent at a dose of 0.1 mmol/kg except
      in hydronephrosis, where a dose of 0.05 mmol/kg was used. Magnetic resonance (MR)
      images were obtained with a 1.5T or a 2.0T magnetic field strength MRI unit. The
      signal intensity of the stroke lesions was increased after administration of
      gadodiamide injection in SHRSP and MCA-occluded rats. Hepatocellular carcinoma
      was undetectable without the use of the contrast agent, but the signal intensity
      of the tumor increased after administration of the gadodiamide injection,
      allowing the lesions to be detected. The signal intensity of the renal medulla
      increased in the non-ligated kidney, but not in the hydronephrotic kidney. The
      information given by the post-contrast images were superior to those obtained
      from the pre-contrast images in all the models. Contrast effects in SHRSP and MCA
      occluded rats were related to differences in capillary permeability, those in
      rats with hepatocellular carcinoma depended on differences in vascularity, and
      those in hydronephrotic rats depended on blood flow and permeability.

PMID- 8741260
TI  - Immunohistological evaluation on respiratory lesions of pigs intranasally
      inoculated with Actinobacillus pleuropneumoniae serotype 1.
AB  - Nine-week-old pigs were inoculated intranasally with 6.10 X 10(3) (group 10(3)),
      10(5) (group 10(5)) and 10(7) (group 10(7)) colony-forming unit of Actinobacillus
      pleuropneumoniae (App) serotype 1 designated HA-337 strain, respectively. One pig
      in group 10(5) and 2 pigs in group 10(7) died with dispnea and hemorrhagic
      pleuropneumonia within 20 to 48 hr post inoculation (PI). All pigs necropsied on
      7 days in groups 10(5) and 10(7) had focal fibrous pleuropneumonia.
      Histologically, pulmonary lesions were classified into three stages; peracute,
      acute and subacute. Fatal cases in group 10(7) had peracute lesion composed of
      severe edema, hemorrhage and necrobiosis of alveoli, with mononuclear cells
      infiltration in the dilated interlobulus. The fatal case in group 10(5) had acute
      pulmonary lesion composed of focal or linear infiltration of round and fusiform
      cells that frequently showed swirling pattern in alveoli. The surviving cases in
      group 10(5) and 10(7) had subacute lesion composed of multifocal pulmonary
      necrosis surrounded by fibrous tissue. The swirling pattern was clearly seen in
      demarcation zone. Immunohistochemically, App antigens scattered as intact
      bacteria in alveoli, dilated interlobular septa and pleura, and lymph vessels in
      peracute and acute lesions. Areas of necrosis were also stained weakly. Although
      no antigen was detected in cytoplasm of macrophages and infiltrated cells in
      peracute lesions, App antigen was detected as positively stained mass in
      cytoplasm of some macrophages in acute lesions. In subacute lesions, App antigens
      were recognized as intact bacteria in necrotic areas and among the swirling
      pattern cells of demarcation zone. Macrophages had App antigens as a large mass
      of pigment in the cytoplasm in area of fibrosis.

PMID- 8741261
TI  - Potential transforming-ability by internal deletion of the bovine c-myb gene.
AB  - Two kinds of bovine c-Myb, the 75 kDa full-length (FL) c-Myb from the thymic type
      of sporadic bovine lymphosarcoma (SBL) cells, and 65 kDa deleted (DEL) c-Myb,
      which is an internally deleted form (85 amino acids corresponding to the negative
      regulatory domain) from calf-type SBL were found. To investigate the relationship
      between internal deletion and transforming capacity, we constructed retroviral
      vectors carrying cDNA that encoded either FL- or DEL-Myb protein, and transfected
      them to mouse fetal liver cells. In spite of the high trans-activating capacity
      of DELMyb, DELMyb and FLMyb showed no significant difference in oncogenic
      capability by measurement of colony formation in soft agar or in methylcellulose
      medium. Thus, the internal deletion of the c-myb gene is competent for
      transactivation but not directly relevant to transformation of mouse hemopoietic
      cells.

PMID- 8741262
TI  - Experimental studies on bovine Hyena disease induced by administration of
      excessive vitamin AD3E premix, vitamin A, or vitamin D3.
AB  - The effects of the excessive administration of the vitamin AD3E(V-AD3E) premix,
      vitamin A (V-A) or vitamin D3 (V-D3) on experimental development of Hyena disease
      in the calves were examined. Hyena disease was recognized in 4 calves, both of
      the 2 calves administered a high dose of V-AD3E premix (V-A 3,000,000, V-D3
      300,000, and V-E 1,200 IU/day, V-AD3E group), 1 of the 2 calves administered a
      half dose of the V-AD3E premix, and 1 of the 2 calves administered only V-A (V-A
      3,000,000 IU/day, V-A group) when each vitamin was administered orally for 10
      days from 1 week after birth. Both of 2 calves administered only V-D3 (V-D3
      300,000 IU/day) did not developed. In the 4 calves with Hyena disease (Hyena
      calves), the plasma retinylpalmitate showed high values which was suggesting the
      hypervitaminosis A, and the epiphysial growth plate was narrow and destroyed
      structure of column. Compared with the Hyena calf in the V-A group, the Hyena
      calves in the V-AD3E group showed earlier appearance time of Hyena disease, lower
      growth rate and shorter lengths of fore and hind limb bones. In conclusion, the
      present findings suggested that excessive V-A administration to suckling calves
      might cause Hyena disease by V-A effects to the epiphysial growth plate, moreover
      such effects may be promoted by the V-D3.

PMID- 8741263
TI  - Plasminogen activator activity in the bovine oocyte-cumulus complex and early
      embryo.
AB  - In this study fibrinolytic assay systems were used to assess the plasminogen
      activator (PA) potential and plasmin generating ability of oocyte-cumulus
      complexes isolated from preovulatory bovine follicles (2-8 mm diameter) and of
      fertilized oocytes from the day of fertilization up to, and including, the
      hatched blastocyst stage (day 12). During embryo development, the culture medium
      was changed every 24 hr and samples examined for PA activity. Irrespective of the
      stage of maturity, no plasminogen or PA could be detected in unfertilized oocytes
      from which the cumulus layer had been removed. Both plasminogen and PA were found
      in the cumulus layer indicating that this, rather than the oocyte, was the source
      of these proteins in the oocyte-cumulus complex. Following oocyte fertilization,
      no PA activity was detected in either the developing embryo or in the culture
      medium before day 7. When the embryos had developed to the expanded blastocyst
      stage, days 7-8, PA production began with activity being detected in both the
      embryos and their culture medium. Between days 8 and 12, when embryos had reached
      the hatched blastocyst stage, the PA activity had increased significantly
      (p<0.05). Analysis of the culture media confirmed this increase in production of
      PA activity and, based on zymography, it was estimated that the molecular weight
      of the PA was 78 k daltons.

PMID- 8741264
TI  - Activation of canine monocytes and polymorphonuclear cells by serum thymic factor
      (FTS) in vivo.
AB  - The effect of serum thymic factor (FTS) was evaluated from the immunoresponse
      augmented in canine monocytes and polymorphonuclear cells (PMN) using the
      chemiluminescence technique. FTS did not affect the number of leukocytes and
      differential count of leukocytes. CL activity of the whole blood was
      significantly elevated by FTS from 72 hr to 120 hr after administration (p <
      0.05), and that at 96 hr after administration was about 3-fold higher than that
      before the administration. The CL response of PMN was significantly elevated by
      FTS administration from 24 hr to 96 hr after administration (p < 0.05), and that
      at 48 hr after administration was about 7-fold higher than prior treatment. FTS
      also significantly elevated the CL response of monocyte from 24 hr to 96 hr after
      administration (p < 0.01), and the CL count of monocyte in 24 hr and 48 hr was
      about 100-fold higher than that before FTS administration. These findings
      suggested that FTS may be efficacious and useful immuno-potentiator for canine
      monocytes and PMN.

PMID- 8741266
TI  - An immunohistochemical study on the innervation of two peptidergic (NPY and VIP)
      nerves in the cerebral arterial tree and choroid plexus of the newt (Amphibia:
      Urodela).
AB  - The pattern of neuropeptide Y (NPY)- and vasoactive intestinal polypeptide (VIP)
      immunoreactive (IR) innervation was investigated in the cerebral arterial tree
      and choroid plexus of the newt by the use of an indirect immunofluorescence
      technique combined with chemical sympathectomy (6-OHDA). The data presented here,
      in conjunction with histochemical data reported previously, showed the following
      characteristic features of cerebrovascular innervation in this urodelan species.
      (1) The cerebral arterial tree and choroid plexus had unbalanced NPY-IR and VIP
      IR innervation, characterized by the absence or a markedly lesser density of VIP
      IR nerves. (2) All or nearly all of the NPY-IR nerves were sympathetic in nature.
      (3) A few cerebral perivascular NPY-IR nerves in some individuals originated from
      the sympathetic NPY-IR nerve cells intrinsic to the major cerebral arteries of
      the anterior circulatory system. (4) Acetylcholinesterase-positive neurons
      lacking both NPY and VIP immunoreactivities are a major nerve type in
      cerebrovascular parasympathetic innervation. The preferential NPY-IR innervation
      of the plexus microvascular-epithelial regions must be considered in relation to
      its special functions, such as the regulation of microcirculation, and
      cerebrospinal fluid (CSF) production and transportation. CSF is vital for the
      movement of nutrients and metabolites in the newt brain.

PMID- 8741265
TI  - Spermatogenic cycle in the testis of the Japanese black bear (Selenarctos
      thibetanus japonicus).
AB  - Spermatogenic cycle in the testis of the japanese black bear (Selenarctos
      thibetanus japonicus) was studied by light and transmission electron microscopy.
      By light microscopy, spermatids were allocated into eleven steps based on
      morphological changes in the nucleus and the acrosome of spermatids. Cellular
      associations of the seminiferous epithelium were allocated into eight stages
      based on the changes in the nucleus and acrosome of spermatids, appearance of
      meiotic figures and time of spermiation. Cross-sections of the seminiferous
      tubule seldom contained more than one type of stage. Spermatids at steps 1-2 had
      the well-developed Golgi complex. The crescent-shaped Golgi complex was
      accompanied by the acrosome extending over the nucleus at steps 3-5. At step 6,
      spermatids faced the base, and the outer membrane of the acrosome converged upon
      the plasma membrane of spermatids. The acrosome projected into the cytoplasm of
      Sertoli cells at step 9. At step 11, most of the cytoplasm was phagocytosed by
      Sertoli cells, and spermatids were released in the lumen to become spermatozoa.

PMID- 8741267
TI  - Effects of depletion of T cell subpopulations on the course of infection and anti
      parasite delayed type hypersensitivity response in mice infected with Babesia
      microti and Babesia rodhaini.
AB  - To elucidate the role of T cell subpopulations in the protective cell-mediated
      immune response at the initial phase of infection with Babesia microti (BM) and
      B. rodhaini (BR), the changes in the course of infection and anti-parasite
      delayed type hypersensitivity (DTH) response after BM or BR inoculation were
      investigated in Lyt-2+ T cell or L3T4+ T cell-depleted mice. Depletion of Lyt-2+
      T cells strongly enhanced the resistance to BM infection, whereas it increased
      the susceptibility to BR infection. In contrast, depletion of L3T4+ T cells
      increased susceptibility to BM infection, while it enhanced resistance to BR
      infection. The anti-parasite DTH response in BM-infected mice was significantly
      enhanced by depletion of Lyt-2+ T cells, while significantly reduced by depletion
      of L3T4+ T cells. No effects of depletion of either Lyt-2+ or L3T4+ cells on DTH
      response was observed in BR-infected mice. From these results, it was suggested
      that the roles of Lyt-2+ and L3T4+ T cells in the protective cell-mediated immune
      response at the initial phase of infection were different between BM- and BR
      infected mice, resulting in the difference in their course of infection.

PMID- 8741268
TI  - Effect of positive end-expiratory pressure on extravascular lung water and
      cardiopulmonary function in dogs with experimental severe hydrostatic pulmonary
      edema.
AB  - The effects of ventilation at positive end-expiratory pressure (PEEP) on
      extravascular lung water (EVLW) and cardiopulmonary function were studied in dogs
      with experimental severe hydrostatic pulmonary edema, which was generated by
      inflating a left atrial balloon and simultaneously injecting warm 5% glucose
      solution into the pulmonary artery. The EVLW was measured by the double indicator
      dilution method using heat and sodium ions. All the dogs were ventilated at zero
      end-expiratory pressure (ZEEP) until the EVLW had increased by 200-300% (maximal
      edema), when they were divided into two groups, one of which (n = 6) was
      ventilated at a PEEP of 10 cm H2O throughout the 4 hr study period (PEEP group)
      and the other (n = 6) was maintained at ZEEP during their survival period (ZEEP
      group). All the dogs in the PEEP group survived ventilation for 4 hr, whereas all
      those in the ZEEP group died within 3 hr, (2 within 1 hr, 1 between 1 and 2 hr
      and 3 between 2 and 3 hr). The EVLW of the PEEP group remained unchanged
      throughout the 4 hr study period, whereas that of the ZEEP group showed a
      tendency to increase. The arterial oxygen tension (PaO2) increased significantly
      throughout the 4 hr period of ventilation in the PEEP group but tended to
      decrease in the ZEEP group. In conclusion, PEEP improves gaseous exchange, but
      does not decrease the EVLW in dogs with experimental severe hydrostatic edema.

PMID- 8741269
TI  - Detection of antibodies against porcine reproductive and respiratory syndrome
      (PRRS) virus in swine sera by enzyme-linked immunosorbent assay.
AB  - We developed an enzyme-linked immunosorbent assay (ELISA) to detect antibodies
      against PRRS virus in swine sera. The ELISA antigen was prepared from MARC-145
      cells infected with PRRS virus. The results from serial serum samples from
      experimentally infected and random swine indicated that the ELISA was more
      sensitive than indirect fluorescent and immunoperoxidase monolayer assays. Since
      the ELISA enables many sera to be simultaneously and rapidly tested, it was
      useful for detection antibodies against PRRS virus in swine sera.

PMID- 8741270
TI  - Detection of turkey rhinotracheitis virus from chickens with swollen head
      syndrome by reverse transcriptase-polymerase chain reaction (RT-PCR).
AB  - We developed a sensitive and specific method, reverse transcriptase-polymerase
      chain reaction (RT-PCR) method, for detection of turkey rhinotracheitis virus
      (TRTV). Two sets of primers were designed from F protein gene sequence of TRTV 3B
      strain. Sensitivity of detection by nested PCR with the primers corresponded to
      0.4 TCID50. Applying this method to a field case of swollen head syndrome (SHS),
      TRTV could be detected directly from chicken trachea and turbinates. It was
      identified that this method was very useful to examine the relation of TRTV and
      SHS.

PMID- 8741271
TI  - Chemiluminescence response of cervine neutrophils to various stimuli.
AB  - The chemiluminescence response of cervine neutrophils to various stimuli was
      investigated in comparison with that of bovine and human homologues. The cervine
      cells showed a strong and consistent response, as observed in other species, to
      opsonized zymosan, phorbol myristate acetate and concanavalin A. The cells,
      however, like bovine homologues, failed to respond to n-formyl-methionyl-leucyl
      phenylalanine which is a potent stimulant of human neutrophils.

PMID- 8741272
TI  - Passage of chicken egg yolk antibody treated with hydroxypropyl methylcellulose
      phthalate in the gastrointestinal tract of calves.
AB  - Two types of chicken egg yolk antibody samples for oral passage trials in calves
      were prepared: (1) hydroxypropyl methylcellulose phthalate (HPMCP) antibody
      powder (HAP)--a powder produced by spray-drying a supernatant obtained after
      precipitation of lipids from egg yolk with HPMCP and (2) control antibody power
      (CAP)--a powder produced from an antibody solution with HPMCP. Antibody activity
      and pattern of distribution of both antibody preparations in the gastrointestinal
      tract of calves were compared by enzyme-linked immunosorbent assay. At 2 hr post
      administration, anti-K99 fimbrial antibodies from both the CAP and the HAP were
      detected in the abomasum of calves with titers of 1:128 and 1:256, respectively.
      However, at 4 hr, anti-K99 fimbrial titers of the CAP and the HAP were reduced to
      1:2 and 1:64, respectively, due to digestion in the abomasum. These results
      indicated that the egg yolk antibody powder with HPMCP was more resistant against
      gastric juice in the stomach, thereby, ensuring a transfer of functional
      antibodies to the small intestine of calves after oral administration.

PMID- 8741273
TI  - An enzyme-linked immunosorbent assay (ELISA) for the detection of antibody
      against Streptococcus suis type 2 in infected pigs.
AB  - An ELISA test for the detection of antibody against S. suis type 2 in pigs was
      developed and applied to field sera. The best sensitivity and specificity of
      ELISA were obtained when a purified polysaccharide antigen was used. It showed no
      cross reaction with sera against other serotypes of S. suis and other pathogenic
      bacteria. A total of 264 sera were collected from 20 pig farms and examined with
      the antibody against S. suis type 2. In the affected farms, 17.0% of pigs tested
      were positive, 9.8% in the adjacent farms, but only 3.4% in the free farms. The
      difference of the positive percentages between the affected and the free farms
      was statistically significant (P < 0.05).

PMID- 8741274
TI  - A new type of cell death, the protruded type, observed in the adrenal gland of
      normal rats.
AB  - Apart from apoptosis, a type of parenchymal cell death by the cell protruding
      into the capillary lumen was observed in the adrenal gland of normal Sprague
      Dawley rats. Ultrathin sections were prepared in the conventional manner and were
      examined by electron microscopy. The protruded cells (p-cells) had the electron
      lucent cytoplasm and the p-cells with ruptured cell membranes were observed in
      the capillaries. The egress of p-cells was either through the endothelial gaps,
      or following the rupture of capillary endothelia. The cytoplasmic matrices of the
      dying p-cells were seen to scatter in the capillary lumen where the nuclei,
      mitochondria and granules remained morphologically intact. The p-cells were seen
      in the capillaries of medulla, but restricted to those of zona reticularis in the
      cortex.

PMID- 8741275
TI  - Characteristics of major structural protein coding gene and leader-body sequence
      in subgenomic mRNA of porcine reproductive and respiratory syndrome virus
      isolated in Japan.
AB  - Nucleotide sequence, 1713nt in length, of porcine reproductive and respiratory
      syndrome virus (PRRSV) isolated in Japan was determined. The sequence encompassed
      3 overlapping open reading frames (ORFs), ORF5 to ORF7. These ORFs encodes major
      structural proteins of PRRSV. The deduced amino acid sequence of each ORF showed
      higher than 87.5% identity with an American isolate, and lower (54.6 to 80.5%)
      identity with an European isolate. This result supported a previous report about
      antigenic characteristics of the EDRD-1 strain. Leader-body junction sequence in
      subgenomic mRNA of the EDRD-1 strain was determined by sequencing cDNA clones of
      subgenomic RNAs. A common sequence motif of 5 nucleotide, represented by
      UA(A/G)CC, was identified as the junction sequence.

PMID- 8741276
TI  - Congestive heart failure due to bilateral atrioventricular valve insufficiency in
      two dogs.
AB  - Congestive heart failure resulted from bilateral atrioventricular insufficiency
      was diagnosed in two, small breed, intact male aged dogs. In both cases, the
      clinical signs were mainly associated with right heart failure, while those
      related to left heart failure were seldom observed. Radiographic and
      echocardiographic examinations revealed the dilatation of the right heart due to
      tricuspid valve insufficiency. Mitral regurgitation was also observed without
      pulmonary hypertension. Both patients responded to medications of diuretics,
      methyldigoxin and angiotensin converting enzyme inhibitor. As congestive signs
      deteriorated, they became unresponsive to the treatment. Ultimately, the dogs
      died 9 and 13 months later from the first admission.

PMID- 8741277
TI  - Isolation of porcine respiratory coronavirus from pigs affected with porcine
      reproductive and respiratory syndrome.
AB  - Four cytopathogenic viruses were isolated in CPK cells derived from porcine
      kidneys from tonsils and lungs of 3 of 15 pigs affected with porcine reproductive
      and respiratory syndrome virus. Physicochemically and morphologically, the
      isolates were similar to a coronavirus. The isolates were not distinguished from
      transmissible gastroenteritis virus (TGEV) by a neutralization test using
      polyclonal antibodies, but differentiated from TGEV by monoclonal antibodies
      capable of discriminating between TGEV and porcine respiratory coronavirus
      (PRCV), indicating that the isolates were PRCV. In a serological survey of 30
      serum samples each collected from about 50 days old pigs in the 2 affected farms,
      29 (97%) and 15 (50%) sera were positive for neutralizing antibody against the
      isolate with the titers ranging from 2 to 64, respectively.

PMID- 8741278
TI  - [Examination of the courses of the arteries in the axillary region. II. The
      course of the axillary artery in the case of Adachi's C-type brachial plexus].
AB  - Muller (1904) stated that the axillary artery in the case of Adachi's C-type
      brachial plexus (AxC) might be derived from the 9th segmental artery. Yamada
      (1967) named a type of the subscapular artery (Sbs) "the superficial subscapular
      artery" which arose from the normal axillary artery (Ax), crossed over the medial
      cord of the brachial plexus and then gave off the lateral thoracic artery (TL).
      He considered that it might be derived from TL and develop to form AxC by
      compensating the less developed normal Ax. We reexamined the courses of Sbs and
      Ax and distinguished three types (S-, I-, and P-type) of Sbs according to their
      origin and course. Then we stated that the mechanism of formation of Sbs
      variations could be explained by the combination between the three stem parts and
      the common peripheral arterial network (Sbs system) (Aizawa et al. 1995).
      Therefore, the purpose of this study was to justify the validity of Muller (1904)
      and Yamada (1967) and to clarify the origin of AxC by applying the concept of Sbs
      system. The materials were 15 cases of AxC and 7 cases of incomplete AxC (AxC).
      The results were as follows. 1) The course of AxC was divided into four parts. 2)
      Two types of AxC were discerned according to the course against the nerve bundle
      communicating from the medial cord to the radial nerve (FM-R). They are the type
      1 AxC which does not pass between the FM-R and the radial nerve, and the type-2
      AxC which dose pass between them. 3) The first part included the branching points
      of the thoracoacromial artery in all cases and the superior superficial brachial
      artery (BSS) in 8 cases. The BSS passed between C7 and C8 of the roots of Ansa
      pectoralis (50%) in about the same manner as BSS from the normal axillary artery
      (Ax). On the other hand, the point where Ax or AxC penetrated the ventral stratum
      of the brachial plexus was examined in 156 cases. The data except those of the
      AxC cases displayed a symmetrical distribution having a sharp peak in C7-C8
      (79.5%) and were not compatible with the incidence of AxC penetrating lower than
      Th1 (7.7%). Therefore, it was difficult to conclude that the first part of AxC
      was derived from the 9th segmental artery. 4) The second part crossed over the
      medial cord and gave off TL in almost all the cases. Therefore, this part was
      considered to include the S-point where the S-type Sbs system (Yamada's
      superficial subscapular artery) arose and to be derived from TL. 5) From the S
      point, while the S-type Sbs system immediately ran down to the deep region of the
      axilla, AxC traversed the axilla passing in front of the thoracodorsal nerve to
      reach the point where AxC was sandwiched between the ventral and the dorsal
      stratum of the brachial plexus. Therefore, the following course from the S-point
      of AxC (the third part) was different from that of the S-type Sbs system. From
      the third part of AxC, the I-type Sbs system arose in 15 cases, and both the
      subscapular branch (RS: *) and the branch to the coracobrachial muscle (CB) were
      often given off. They were the same branches as those which arose from the I
      point of normal Ax, and type-2 AxC passed between FM-R and the radial nerve in
      this part. Therefore, it was considered that the third part included the I-point
      of the normal Ax and, moreover, AxC recovered the normal course of Ax at the I
      point. 6) The fourth part of AxC included the P-point where the P-type Sbs system
      branched off from AxC in 7 cases. The course of the fourth part of AxC had
      exactly the same course as that of normal Ax. 7) It was elucidated that the first
      part, the distal half of the third part, and the fourth part of AxC were exactly
      the same as normal Ax, the second part was derived from TL, and the proximal half
      of the third part from the S-point to the I-point was unique in AxC. Recently,
      however, the reverse course of the unique part of AxC has appeared as the deep
      lateral thoracic artery (TLp) (Aizawa et al. 1995) in rare cases. 8) In co

PMID- 8741279
TI  - [The replacement processes of growth plate cartilage to bone in endochondral
      ossification of mandibular condyle].
AB  - Using 3-week-old male beagle dogs, we examined the cartilage-bone replacement
      processes in the mandibular condyle by means of light and electron microscopy.
      Calcification of the cartilage matrix occurred in the central area of the
      longitudinal septa, but not in the transverse septa. Perivascular mononuclear
      cells absorbed the transverse septa which initiated the opening of the
      chondrocytic lacunae. These cells phagocytosed septal cartilage fragments.
      Shortly thereafter, a thin bone layer was deposited on the remaining longitudinal
      septa by invading osteoblasts. Osteoclasts in lacunae developed neither ruffled
      borders nor clear zones in the cartilage matrix, but once the bone layer has been
      deposited in the remaining cartilage, these structures formed. Our results
      suggest that the cartilage-bone replacement in mandibular condyle involves three
      sequential processes: 1) degradation and phagocytosis of cartilage fragments in
      the transverse septa by mononuclear cells, 2) bone deposition over the remaining
      longitudinal septa, and 3) degradation of both calcified cartilage and bone by
      osteoclasts.

PMID- 8741280
TI  - Reduplication of swine spleen lobes.
AB  - In a search for the reduplication of the spleen, a total of 227,513 swine from
      130 breeders were surveyed at a slaughterhouse (Ozu Health Center, Ehime
      Prefecture, Japan) between October 1993 and June 1995. They were 6 to 7 months
      old and their body weight ranged from 95 to 120 kg. Twenty swine had two lobed
      spleens. Of these, nine were males and 11 were females. The second or sub-lobe
      was generally smaller than the main lobe but was variable in size. Large ones
      were similar in size to the main lobe and small ones were approximately 1/4 of
      the length of the main lobe. One very small lobe was just a protrusion of the
      main one across the greater omentum. The two lobes were always attached to each
      other in the central portion, and fat and the greater omentum were always found
      between the lobes. The splenic artery, vein and nerve were shared between the two
      lobes. The main lobe was covered with peritoneum from the parietal surface of the
      stomach while the sub-lobe was covered with visceral peritoneum. Both peritonea
      joined to the greater omentum at the hilus in ordinary spleens, but at short
      distance from the hilus in double lobed spleens.

PMID- 8741281
TI  - Bicuspid aortic valve in an adult human cadaver: a case report.
AB  - We encountered a "bicuspid" aortic valve in an 83-year-old man. This valve
      consisted of two semilunar leaflets, anterior and posterior, though they were
      extensively calcified. The right and left coronary arteries independently arose
      from the anterior aortic sinus. The infundibular ligament ran from the pulmonary
      trunk at the commissure of the right and left semilunar cusps to the aorta at the
      mid-point of the anterior sinus. These findings strongly suggests the present
      bicuspid aortic valve may be formed by fusion of usual right and left (coronary)
      cusps. No other congenital anomalies were noted in this heart.

PMID- 8741282
TI  - [A model for embryological instruction of the digestive tract].

PMID- 8741283
TI  - [Scarce anatomical textbook by professor Buntaro Adachi].

PMID- 8741284
TI  - [A study on relapse of schizophrenic patients--10-year-follow-up investigation
      after initial admission].
AB  - Ten year prognosis of schizophrenic patients after their initial admission was
      studied. The subjects of the present investigation were 106 schizophrenic
      patients who fulfilled the criteria for schizophrenia of DSM-III-R and were
      initially admitted to a hospital between January 1979 and December 1984. They
      were classified into following five groups: 1) a discontinuing group (39 patients
      who could not be followed up because of changing the hospital or ceasing
      outpatient treatment), 2) an unrelapsing group (29 patients who had no relapse in
      continuing medication), 3) an A group (13 patients who relapsed in spite of
      continuing medication), 4) a B group (22 patients who relapsed only after
      discontinuing medication), and 5) a C group (3 patients who relapsed in
      continuing medication as well as after discontinuing medication). These groups
      were compared in multiple domains such as age at onset, age on initial admission,
      duration from onset to initial admission, etc. The average age at onset was
      significantly older in the unrelapsing group (29.0 years) than in the A group
      (22.1 years) (p < 0.05). The average age on initial admission was significantly
      older in the unrelapsing group (35.2 years) than in the A group (25.0 years) (p <
      0.01). Furthermore the average duration from onset to initial admission was
      significantly longer in the unrelapsing group (70.9 months) than in the A group
      (23.8 months) (p < 0.05). Assuming theoretical groups considered in points of
      tendency of relapse and the effect of neuroleptics on the prevention in each
      patient, as well as theoretical subgroups considered in points of biological
      pathology and nonbiological pathology as factors of relapse, the following two
      subgroups were abstracted from the groups of this study: a subgroup with a high
      effect of medication on the prevention of relapse and the other with a low
      effect. There were significant differences in the average age at onset, age on
      initial admission, duration from onset to initial admission, and duration of
      initial admission between these two subgroups. These different onset pattern
      suggest that the effect of medication on relapse is different among patients. Our
      results indicate existence of a group of schizophrenic patients whose relapse can
      not be prevented by current neuroleptic therapy.

PMID- 8741285
TI  - [Manifestation of the symptoms in demented patients after the Great Hanshin
      Earthquake in Japan].
AB  - On Jan. 17, 1995, at 5:46 a.m., an earthquake measuring 7.2 on the Richter scale
      shook southern area of Hyogo prefecture of Japan, including Kobe city. By this
      earthquake referred as the Great Hanshin Earthquake later, over 6,000 people were
      killed, 150,000 buildings and houses were destroyed and more than 300,000 people
      were temporally evacuated. Over a half of victims were reported to be elderly. We
      reported five survivors with senile dementia of the Alzheimer's type, who showed
      exacerbation or manifestation of their dementia symptoms after the quake. None of
      them had been injured and none of their close relatives had been killed or
      injured. They had been living in the downtown of Kobe for over 30 years before
      the disaster. Most of them had lived by themselves. Their severity of dementation
      were mild to moderate. They had been living without any problems and functioning
      fairly well. Their sons and daughters did not realize that their fathers or
      mothers had dementia before the earthquake. They had to move to and live with
      their son's or daughter's families, since their residences were destroyed by the
      earthquake. Shortly after that, they showed exacerbation or manifestation of
      their symptoms and developed delusion that their money and valuables were stolen
      by their daughters or daughters-in-law. We concluded that: they had been living
      without any problems and functioning fairly well, although they had had mild
      dementia symptoms; their living by themselves in communities familiar to them
      prevented manifestation of dementia symptoms; living together with son's or
      daughter's family easily promoted the development of delusion that their property
      was stolen by their close relatives, especially daughters or daughters-in-law in
      demented people.

PMID- 8741286
TI  - [Survey and treatment strategy of antidepressant-resistant depression].
AB  - The present study investigated the phenomenology and treatment of antidepressant
      resistant depressions (ARD). To be classified a nonresponder, a patient had to
      have been treated adequately with two tricyclic (or tetracyclic) antidepressants
      (i.e., a minimum of the equivalent of 150 mg of imipramine for 4 weeks). The 34
      depressed patients (25 unipolar patients and 9 bipolar patients) failed to
      respond to these antidepressant trials. Seventy-two % of the unipolar patients
      were in their first depression episodes, but 89% of the bipolar patients had 2 or
      more previous affective episodes. The mean duration of the current episode of
      depressions was 3.8 years. In 5 unipolar patients, the duration of the current
      depression episode was 10 years or more. The addition of lithium, bromocriptine
      or levothyroxine treatment to tricyclic or tetracyclic antidepressants were
      effective in the treatment of ARD. Levothyroxine were more effective in the
      treatment of the bipolar patients than the unipolar patients. Safrazine, a
      monoamine oxidase inhibitor, and electroconvulsive therapy were also effective in
      the treatment of ARD, but had the drawbacks of the high incidence of moderate or
      severe adverse reactions and high relapse rates, respectively. We propose a step
      wise approach to the treatment of ARD, which mainly includes the pharmacotherapy
      and can be used in Japan.

PMID- 8741287
TI  - [On the structure of seclusion room as the therapeutic space].

PMID- 8741288
TI  - [Frontiers in sphingolipid research].

PMID- 8741289
TI  - [Sphingomyelin cycle: role in cell functions inducing apoptosis].

PMID- 8741290
TI  - ["Sphingosine pathway": a novel apoptosis inducing pathway].

PMID- 8741291
TI  - [Sphingomyelin and its catabolism in cell nucleus: their possible roles in
      regulation mechanism of DNA replication].

PMID- 8741292
TI  - [Saposins and sphingolipid metabolisms].

PMID- 8741293
TI  - [New approach to glycosphingolipid research by using TLC blotting].

PMID- 8741294
TI  - [MR imaging of bladder tumors using fluid attenuated inversion recovery (FLAIR)
      technique].
AB  - Magnetic resonance imaging (MRI) has been reported valuable for the diagnosis of
      bladder tumors, but does not provide adequate staging of these tumors. Therefore,
      we examined whether the FLAIR technique could be used to improve the diagnostic
      ability of MRI. FLAIR utilizes inversion recovery and can display a lesion as a
      heavy T2-WI by decreasing the signal intensity of water and thus altering the
      contrast at the bladder wall. The inversion time (TI), that gave urine a signal
      intensity of "zero", was determined by theoretical analysis. In addition, MRI by
      the FLAIR technique was performed on 29 patients with bladder tumors. With the
      FLAIR technique, MRI showed a sensitivity of 78.6% and a specificity of 91.7% for
      pT1 or smaller lesions, while the values were respectively 91.7% and 78.6% for
      pT2 or worse lesions.

PMID- 8741295
TI  - [Hautmann's ileal neobladder: experience of 37 cases].
AB  - Between April 1993 and August 1995, a Hautmann's ileal neobladder was created in
      37 men after total cystectomy for bladder cancer. Ureteroileostomy was performed
      using a submucosal tunnel instead of the Le-Duc Camey procedure. There was no
      operative mortality and only a few early complications. The mean postoperative
      follow-up time was 16 months, with a range of 3 to 31 months. Hydronephrosis
      occurred in 3 patients, being caused by stenosis at the uretero-ileo anastomosis
      in 2 and by proximal stenosis in 1. Neobladder-ureteral reflux did not occur in
      any of the patients. Postoperative ileus developed in 3 patients, and one
      required laparotomy. Stenosis of the urethro-ileal anastomosis developed in 3
      patients, who were successfully treated by transurethral incision. Thirty five
      patients achieved daytime continence, while 2 patients had slight incontinence.
      Twenty nine patients achieved nighttime continence, and most of the patients
      awoke 1-4 times to prevent overflow incontinence. The mean maximum flow rate,
      average flow rate and post-voiding residual urine volume were respectively 15.3
      ml/sec, 5.5 ml/sec and 81 ml at 6 months postoperatively, and 14.9 ml/sec, 5.4
      ml/sec and 76 ml at 12 months. Four patients with more than 100 ml of residual
      urine required sterile intermittent catheterization 2-4 times a day. Urethral
      recurrence was detected in 2 patients. One was treated with transurethral
      resection and cisplatinum-based systemic chemotherapy, and the other required
      urethrectomy and urinary diversion using a new continent efferent limb.

PMID- 8741296
TI  - [Clinical studies of inverted papilloma of the bladder].
AB  - Clinical studies were conducted on 9 cases of inverted papilloma of the urinary
      bladder which were transurethrally resected between August, 1987 and July, 1995
      at our hospital, in males between 29 and 81 years of age (mean:58.3). Six of the
      9 inverted papillomas were localized at the bladder neck and 3 in the trigone.
      Cystoscopic examinations revealed that inverted papillomas were divided into two
      types, one with a thick and short stalk with a smooth surface and the other with
      a thin and long stalk with/without a partial papillary surface. The majority of
      the former was located in the trigone and all of the latter cases in the bladder
      neck, suggesting that the two types occurred at different sites. Pathological
      examination by Hematoxylin-Eosin staining demonstrated that 5 of the 9 cases were
      of the trabecular type and 4 were of the grandlar type. Immunohistochemically,
      none of the tumors were stained with the antiprostatic-specific-antigen antibody
      revealed. Follow-up periods after the operation were from 12 to 48
      months(mean:26.6 months) and no recurrence was observed.

PMID- 8741297
TI  - Sclerotherapy of testicular hydroceles with 3% aqueous phenol.
AB  - With the evolution of minimally invasive approaches in medicine, phenol has
      regained its popularity for the sclerotherapy of testicular hydroceles. Together
      with reported efficiency and safety of 2.5% phenol in the literature, the
      recently proved safety of 3% phenol in esophageal variceal sclerotherapy has led
      us to perform a prospective study to lessen the number of sessions. Sclerotherapy
      with 3% aqueous phenol was applied on an ambulatory basis to 23 patients with 31
      hydroceles, who were over 40 years old and who had no fertility problems. The
      over-all cure rate was 96% with an average follow-up of 3 years, and 58% of the
      hydroceles required only one session of treatment. The average number of
      treatment sessions was 2.2 (range; 1-7). One patient with a history of
      herniorraphy 10 years earlier, was treated surgically following failure of seven
      sclerotherapy sessions. Phenol, a sclerosant superior to other conventional
      agents including tetracyclines, requires neither anesthetics nor prophylactic
      antibiotics. Our findings indicate that sclerotherapy with 3% phenol is an
      effective, economical and safe form of therapy for patients with hydrocele.

PMID- 8741298
TI  - [Clinical study of Silver Lubricath Foley catheter].
AB  - We evaluated the Silver Lubricath Foley Catheter (silver catheter) coated with
      silver and hydrogel developed to prevent urinary infection, in comparison with
      the silicone-coated catheter (silicone catheter). Twelve patients ranging from 71
      to 95 years of age (median age, 82 years) were catheterized and the 16 of 18F
      catheter was replaced every 2 weeks. They answered a questionnaire which included
      inquiry about the treatment with urinary catheter. Because of less leakage and
      discomfort to the urethra, the silver catheter had advantages over the silicone
      catheter. The risk of bacteriuria after 14 days of catheterization was not
      significantly different between the two types of catheter. Scanning electron
      microscopic analysis revealed that bacterial biofilm developed on the inner
      surface of both catheters after 14 days of catheterization. On the other hand,
      the amount of bacterial biofilm on the outer surface of a silver catheter was
      less than that on the outer surface of a silicone catheter.

PMID- 8741299
TI  - [Renal cell carcinoma in childhood: a case report].
AB  - A case of renal cell carcinoma (RCC) in a teenage patient is reported. A 13-year
      old girl visited our hospital with the complaint of dyspnea and right abdominal
      mass. CT scan and chest X-P revealed a right renal tumor with multiple lung
      metastasis. Wilms' tumor was suspected and a combination chemotherapy consisting
      of actinomycin D and vincristin was performed. Since the tumor was insensitive to
      these agents, open biopsy was done. The pathological findings showed clear cell
      renal cell carcinoma. Despite the administration of alpha interferon, 5-FU and
      cimetidine, the disease was progressive and the patient died 5 months after
      diagnosis. It is important to consider the possibility of renal cell carcinoma in
      teenage patients with a renal mass, since more than 40% of the renal tumors in
      this age group are renal cell carcinomas.

PMID- 8741300
TI  - [Retroperitoneal abscess formation accompanied by intraabdominal free air, a rare
      complication of transcatheter arterial embolization of renal tumor: a case
      report].
AB  - Transcatheter arterial embolization (TAE) has been commonly used in the treatment
      of renal cancer. Postembolization syndrome consisting of fever, flank pain and
      gastrointestinal symptoms is encountered in almost every case. We report a case
      of E. coli-induced retroperitoneal abscess accompanied by intraabdominal free air
      which developed three weeks after TAE in a 59-year-old woman with T4N0M0 renal
      cancer. No fistula between abscess and gastrointestinal tract could be
      demonstrated by gastrofiberscopy and barium enema. Urine culture just before TAE
      should be examined to avoid such a complication.

PMID- 8741301
TI  - Metastatic choriocarcinoma of the kidney discovered by refractory hematuria.
AB  - A case of metastatic choriocarcinoma of the kidney is reported. A 34-year-old
      married woman was referred to our department complaining of gross hematuria,
      fever and loin pain. Computed tomography revealed a right renal tumor with mixed
      density and multiple lung metastases. We performed nephrectomy to control
      refractory hematuria. The histological diagnosis of the tumor was metastatic
      choriocarcinoma. In young women, with gross hematuria, menstrual irregularity and
      atypical renal tumor with multiple lung metastases, metastatic choriocarcinoma of
      the kidney should be suspected.

PMID- 8741302
TI  - [Squamous cell carcinoma of the renal pelvis associated with renal stones in a
      patient with chronic renal failure: a case report and a review of the Japanese
      literature].
AB  - A case of squamous cell carcinoma of the left renal pelvis associated with
      chronic renal failure on hemodialysis is reported. The patient, a 59-year-old
      man, had undergone bilateral nephrolithotomy, in 1966, followed by right
      ureterolithotomy and bilateral percutaneous nephrolithotripsy, but residual
      stones existed. He suffered from left flak pain and fever, and computed
      tomography (CT) and magnetic resonance imaging (MRI) revealed left perirenal
      abscess in July 1994. Percutaneous drainage and antibacterial chemotherapy were
      performed, but his symptoms did not improve. Three months later, CT and MRI
      revealed a mass in the left perirenal space and destruction of the 12th thoracic
      vertebra, which were considered to be infectious changes. On November 9, 1994,
      left nephrectomy was performed. Histopathological diagnosis was moderately
      differentiated squamous cell carcinoma, grade 2, INF-gamma, pT4, pR1, pL0 and
      pV1. In spite of irradiation therapy, he died on January 19, 1995.

PMID- 8741303
TI  - [A case of leiomyoma of the urinary bladder associated with transitional cell
      carcinoma].
AB  - We report a case of leiomyoma of the urinary bladder associated with transitional
      cell carcinoma. A 60-year-old-male was referred to our hospital because of the
      complaint of dysuria and for detailed examination of left hydronephrosis. Drip
      infusion pyelography revealed left uretero-vesico junction stenosis. Flexible
      cystoscopy revealed benign prostatic hypertrophy and epithelial bladder tumor at
      the bladder neck and left ureteral orifice. The tumor was histologically
      diagnosed as TCC (transitional cell carcinoma). M-VAC chemotherapy (methotrexate
      30 mg/m2, day 1, 15, 22, vinblastine 3 mg/m2, day 1, 15, 22, adriamycin 30 mg/m2,
      day 2, cisplatin 70 mg/m2, day 2) was performed as a neoadjuvant chemotherapy.
      However, since pelvic MRI revealed tumor invasion in to the muscle area, total
      cystoprostatourethrectomy and ileal conduit were done. Pathological examination
      of the tumor of left ureteral orifice revealed TCC, G2, INF beta, pT1, ly0, v(-),
      pN0, PM0. The tumor in the bladder neck was histologically diagnosed as
      submuscosal type leiomyoma. No cases of leiomyoma of the urinary bladder
      associated with transitional cell carcinoma have been reported in Japan.

PMID- 8741304
TI  - [A case of genitourinary double cancers detected by health screening].
AB  - A 58-year-old male with left renal cell carcinoma and prostatic carcinoma
      occurring synchronously, is reported. He visited our hospital, because of the
      high level of serum prostate-specific antigen (PSA) pointed out in a health
      screening by his company. Prostatic cancer was detected in both lobes of the
      prostate by needle biopsy specimens and histopathology represented moderately >
      poorly differentiated adenocarcinoma. Magnetic resonance imaging (MRI) and
      computed tomography (CT) revealed no cancer invasion beyond the prostate and no
      lymph node metastasis. Bone scintigram showed no abnormal RI accumulation to
      bone. Therefore, his prostatic cancer was considered to be at stage B2. Abdominal
      ultrasound echogram showed the mass lesion in the left kidney. CT and angiogram
      also demonstrated a left renal tumor. Left radical nephrectomy was performed and
      histopathology showed a mixed subtype of renal cell carcinoma (stage: pT2b, pN0,
      pM0). Although 94 cases of double cancers associated with genitourinary organs
      have been reported in the Japanese literature, only 4 cases of double cancers of
      renal cell carcinoma and prostatic cancer have been reported.

PMID- 8741305
TI  - [A case of penile cancer treated with combination of chemotherapy, radiation and
      radical operation].
AB  - A 60-year-old [correction of 68] male was referred to our hospital because of a
      penile tumor with necrosis. Pathological examination of the penile tumor and
      superficial inguinal lymph nodes in biopsy revealed well differentiated squamous
      cell carcinoma (SCC) and the SCC tumor marker was elevated. TNM classification
      was T2, N2, M0 according to findings obtained by computed tomography (CT) and
      magnetic resonance imaging (MRI). We diagnosed the tumor inoperable radically and
      administered 10 mg peplomycin once a week for 10 weeks intravenously. The SCC
      marker level was not reduced and the tumor was not changed on MRI. Then, we
      performed combined pirarubicin treatment and radiotherapy. The patient received
      linac radiotherapy between 40 Gy/4 weeks/20 fractions. Pirarubicin, 10 mg/m2, was
      administered once a week for 4 weeks during irradiation intravenously. After the
      combined therapy, the SCC marked level was reduced to the normal range and the
      tumor was reduced. We performed radical operation. Pathological diagnosis
      revealed no viable tumor cells. The patient was alive with no evidence of disease
      a year later. This combined therapy is suggested to be useful.

PMID- 8741306
TI  - [Malignant fibrous histiocytoma of spermatic cord: a case report].
AB  - A 52-year-old man presented with a painful, gradually enlarging mass in the left
      inguinal region. An ultrasound examination demonstrated a lobulated, heterogenous
      tumor 6.0 x 4.0 x 3.0 cm in diameter, which separated from the left testis and
      epididymis. Radical inguinal orchiectomy with wide en bloc local resection was
      performed. Histologic diagnosis was a malignant fibrous histiocytoma (MFH) with a
      giant cell variant. The patient underwent postoperative regional irradiation and
      has been alive without metastasis and local recurrence 3 months after the
      operation. Among the 19 patients with MFH of spermatic cord reported in Japan,
      only two cases were of giant cell type of MFH including the present case.

PMID- 8741307
TI  - Adverse events associated with MMR vaccines in Japan.
AB  - The largest nationwide active surveillance of four Measles-Mumps-Rubella (MMR)
      vaccines was conducted in Japan. A total of 1255 pediatricians actively
      participated in the study, which comprised 8.6% of all members of the Japanese
      Pediatric Society. The total number of registered recipients of MMR vaccines was
      38 203. They were arbitrarily given one of the MMR vaccines produced by three
      makers (Takeda, Osaka city, Kitasato Minato-ku. Tokyo and Biken Suita city,
      Japan) or the standard MMR vaccine made of designated strains (Kitasato's measles
      AIK-C, Biken's mumps-Urabe Am9 and Takeda's rubella-To336) produced by Takeda,
      Kitasato and Biken and were observed for 35 days. The rates of virologically
      confirmed aseptic meningitis per 10,000 recipients were 16.6, 11.6, 3.2 and 0 for
      the standard MMR, Takeda MMR, Kitasato MMR and Biken MMR vaccines, respectively.
      The incidence of convulsions between 15 and 35 days was the highest with the
      standard MMR vaccine and the incidence of fever associated with vomiting
      occurring between 15 and 35 days (symptoms relevant to aseptic meningitis) were
      also the highest with the standard MMR vaccine. The incidence of parotid swelling
      was the lowest with Takeda MMR vaccine. This surveillance revealed that
      incidences of aseptic meningitis after administration of the standard MMR vaccine
      and of Biken MMR vaccine were different. This posed questions about the
      manufacturing consistency of the Urabe Am9 mumps virus vaccines. On the other
      hand, the National Institute of Health found that the biological characteristics
      of the Urabe Am9 mumps virus contained in the standard MMR vaccine and in the
      Biken MMR vaccine were different. The Biken Company reported that the mumps
      vaccine in the standard MMR vaccine was a mixture of two Urabe Am9 mumps vaccine
      bulks; one identical to that contained in the Biken MMR vaccine and the other
      produced by a different manufacturing process.

PMID- 8741308
TI  - Clinical features of measles in immunocompromised children.
AB  - Measles is often fatal for immunocompromised hosts. Protective immunity against
      measles has been studied but is still not completely understood. Recently, five
      cases of measles were encountered in immunocompromised children. Two of these
      were allogeneic bone marrow transplanted cases (one common variable
      immunodeficiency and one severe aplastic anemia) in remission, one Wilms' tumor
      case in remission, one hepatoblastoma case after cytotoxic therapy at disease
      onset and one exaggerating hemophagocytic syndrome case with suppressed natural
      killer cell activity. Clinical symptoms, laboratory findings and the immunologic
      backgrounds of these five patients were investigated. One of the patients, an 8
      year old boy with hemophagocytic syndrome, died of giant cell pneumonia which was
      confirmed in the section of necropsy lung specimen. Two other patients who
      received allogeneic bone marrow transplants were not immune to measles, despite
      their own and their donors' immunizations. Their clinical symptoms were rather
      severe but both patients recovered and have remained seropositive for as long as
      13 months. This fatality from measles is the first reported in a patient with
      hemophagocytic syndrome. Suppressed natural killer cell activity may be a poor
      prognostic factor. Also, secondary immunization failure for measles can occur in
      bone marrow transplanted patients with rather severe clinical symptoms.

PMID- 8741309
TI  - Detection of human immunodeficiency virus-1 DNA, RNA and antibody, and occult
      blood in inactivated saliva: availability of the filter paper disk method.
AB  - Eighty three samples of saliva were collected from 60 subjects who were
      asymptomatic carriers of AIDS related complex (ARC) and AIDS. They included
      hemophiliacs, homosexuals and heterosexuals. Occult blood, human immunodeficiency
      virus-1 (HIV-1) antibody and DNA were assayed after heat treatment at 56 degrees
      C by strip method, particle agglutination and polymerase chain reaction (PCR),
      respectively. HIV-1 RNA was assayed by reverse transcription (RT)-PCR after heat
      treatment at 56 degrees C or 90 degrees C, or after application to filter paper
      disks with drying and heat treatment at 90 degrees C. Positive results were found
      in 53% (occult blood), 73% (HIV-1 antibody), 23% (HIV-1 DNA, 56 degrees C), 34%
      (HIV-1 RNA, 56 degrees C), 33% (HIV-1 RNA, 90 degrees C) and 25% (HIV-1 RNA, 90
      degrees C, filter paper disk), respectively. The results did not depend on the
      stage of the disease or the route of infection. Other studies have reported the
      use of the filter paper disk method to detect antibodies against HIV and HIV
      genomes in blood samples. The present study demonstrated that it could also be
      used for the detection of HIV genomes in saliva samples.

PMID- 8741310
TI  - The outbreak of mumps in a small island in Japan.
AB  - A major mumps outbreak occurred on a small island, Ikeshima. in Nagasaki
      Prefecture from August 1994 to February 1995. There were 236 patients with the
      mumps at Ikeshima Miners' Hospital during that period. The Measles-Mumps-Rubella
      (MMR, Toitsukabu) vaccination coverage in the 43 children at the nursery school
      was 65.1% and it was 61.9% in the 21 children aged 4-5 years not attending the
      nursery school. Coverage was 66.6% in the 63 kindergarten students and 53.7% in
      56 first-graders. The overall MMR vaccination coverage among these children was
      61.7% (113/183) from 1989 to 1992. Children from the second grade to junior high
      school received monovalent mumps vaccine, Torii strain. None received Zishakabu
      MMR. The age of the patients ranged from 1 to 43 years, with a mean of 9.1 years.
      The majority (77.5%) were primary school children. The attack rates for
      vaccinated and unvaccinated children in grades one to six were: 6.7% (2/30) and
      88.5% (23/26), 25% (3/12) and 44.1% (30/68), 11.1% (1/9) and 64.4% (29/45), 25%
      (2/8) and 60% (45/79), 22.2% (2/9) and 35.9% (28/78). 0% (0/5) and 24.7% (18/73),
      respectively. The overall frequency in the primary school was 41.4% (183/442
      children). The frequency in the nursery school for children aged 4-5 years was
      14.0% (6/43). It was 17.5% (11/63) in children aged 5-6 years in the
      kindergarten, 5.2% (11/213) in children not attending school with an age range of
      1-5 years, and 4.2% (10/237) in junior high school students. Although the
      frequencies of MMR coverage for the nursery school children and kindergarteners
      were not high enough to eradicate mumps outbreaks, the MMR vaccination program
      was thought to have influenced the low frequency of mumps among the children.
      Close physical interactions among the first-graders would have contributed to
      their high frequency of mumps. Some patients presented with suspected mumps
      parotitis several times, but no such serological confirmation of reinfection was
      obtained.

PMID- 8741311
TI  - Definitions of severely mentally and physically disabled children in Japan: do
      the differences affect the prevalence rates of these children?
AB  - The prevalence rate of severely mentally and physically disabled children (SDC)
      aged 6-15 years in Okinawa prefecture on 1 May 1989 was 0.74/1000 (143/192,038)
      according to Oshima's classification, compared with 0.89/1000 (170/192,038)
      according to the Ministry of Education's classification with minor modifications.
      The number of children in region classes 1, 2, 3 and 4 of Oshima's classification
      for SDC were 100, 34, 6 and 3, respectively. The difference (n = 27) between the
      total numbers of SDC according to the two classifications was mainly because of
      21 children categorized as "walking with support' who were included as SDC
      according to the Ministry of Education's classification but not as SDC according
      to Oshima's classification. Only region class 1 of Oshima's classification
      corresponded with region class 25 of the Ministry of Education's classification.
      The results of the present study indicate that the differences between the two
      definitions of SDC affect the reported prevalence rates of SDC. Therefore,
      changing patterns in the prevalence of SDC should be assessed by serial surveys
      using the same method in each district.

PMID- 8741312
TI  - Clinical and genetic studies of five fatal cases of Japanese Gaucher disease type
      1.
AB  - Five fatal cases of Japanese patients with type 1 Gaucher disease were studied.
      The causes of death included hemorrhage secondary to esophageal varices (two
      cases), respiratory distress (one case), hepatic failure (one case) and
      postoperative sepsis (one case). All of the patients had previous splenectomies,
      four patients had bone involvement and hepatic cirrhosis. The identified Gaucher
      genotypes were 1448C/1213G, 1603T/1603T, 1448C/1390G, and 1213G/1213G. The
      prognosis of type 1 Gaucher disease is generally good. We propose that patients
      with a similar clinical course and genotype to those presented in the present
      study should receive prompt comprehensive treatment. Patients with the 1213G
      mutation, pulmonary and liver involvement and a previous splenectomy should be
      considered as candidates for early vigorous treatment.

PMID- 8741313
TI  - Serum and cerebrospinal fluid zinc levels in children with febrile convulsions.
AB  - The mechanisms underlying febrile convulsions (FC), which have multiple
      etiological factors, are not yet clear. The aim of the present study was to
      determine whether there were any changes in serum and cerebrospinal fluid (CSF)
      zinc (Zn) levels in children with febrile convulsion during seizures. A total of
      102 children were included in the study, with four groups formed as follows:
      group A, 40 children with FC (aged 9 months to 5 years); group B. 20 children
      having fever without convulsion (aged 6 months to 5 years); group C, 20 children
      with afebrile convulsion (aged 6 months to 6 years) and group D, 22 healthy
      children (aged 5 months to 6 years). Serum and CSF zinc levels for groups A, B
      and C and serum Zn levels only for group D were measured. The serum Zn levels of
      17 children in group A were again measured during healthy periods. Serum Zn
      levels of groups A, B, C and D had a mean of 0.70 +/- 0.10 mg/dL, 1.07 +/- 0.08
      mg/dL. 1.26 +/- 0.32 mg/dL and 1.17 +/- 0.21 mg/dL, respectively, and the values
      of group A were lower than those of the other three groups (P < 0.001). In group
      B, serum Zn levels were also lower than those of groups C and D (P < 0.05). The
      CSF Zn levels of groups A, B and C were found to have a mean of 0.07 +/- 0.02
      mg/L, 0.12 +/- 0.02 mg/L and 0.14 +/- 0.04 mg/L, respectively. In group A, the
      CSF Zn levels were lower than those of groups B and C (P < 0.001), and in group B
      they were lower than those of group C (P < 0.05). For the 17 patients in group A,
      serum Zn levels during healthy periods (0.87 +/- 0.10 mg/dL) were found to be
      higher than the values shortly after seizures, but lower than those of groups B,
      C and D (P < 0.001). We could not observe any relationship between zinc levels of
      the serum and CSF and the degree and duration of the fever. These findings
      suggest that serum and CSF Zn levels decreased during infectious diseases, and
      that this decrease was more significant in patients with FC.

PMID- 8741314
TI  - Relationships between clinical and histological profiles of non-familial
      idiopathic neonatal hepatitis.
AB  - Idiopathic neonatal hepatitis (INH) is a syndrome characterized clinically and
      histologically but there is little information concerning the relationship
      between the clinical features and histological findings. In the present study,
      sixty-two patients clinically diagnosed as non-familial INH were histologically
      classified into four groups according to a provisional definition based on
      predominant lesions and examination of their clinical features. Patients of
      cholestasis (n = 23) and giant cell hepatitis (GCH, n = 21) were most frequent
      (37% and 33%, respectively), and patients of fatty liver (n = 10) and hepatitis
      (n = 8) were less common (16% and 13%). The GCH group showed a dominance of male,
      low birthweight, older and breast-fed babies. The cholestasis group demonstrated
      a dominance of male, low birthweight, younger and bottle-fed babies. The
      hepatitis group had the highest frequencies of high-grade hepatomegaly and
      splenomegaly. Fifty six cases completely recovered. Two died of hepatic failure
      in early infancy and four had chronic liver diseases at the age of 12 months. The
      fatty liver group had the worst outcome. Histological features in non-familial
      INH were variable and typical giant cell hepatitis was seen in only one-third of
      patients. Characteristic clinical features in each histologically classified
      group may suggest heterogenous etiologies underlying non-familial INH.

PMID- 8741315
TI  - Ultrasonography for the detection of ureteric reflux in infants with urinary
      infection.
AB  - Several less harmful methods than voiding cysto-urethrography for detecting
      significant ureteric reflux have been proposed. The present prospective study
      investigated whether ultrasonography was effective in identifying ureteric reflux
      in infants with their first febrile urinary infection. The subjects were 27
      infants (24 boys and 3 girls) aged from 0 to 8 months. The urinary tract was
      scanned when the bladder was full, and before and during induced voiding. Infants
      with abnormal ultrasound findings underwent voiding cysto-urethrography. The
      other infants were followed and those who had a recurrence of urinary infection
      underwent voiding cystography. Ten children underwent cysto-urethrography, with
      eight refluxing ureters identified in six boys. Ultrasound revealed transient
      dilatation of the renal pelvis on voiding in five kidneys, transient dilatation
      of distal ureters in 12 and hydro-ureteronephrosis in two. Each of the five
      kidneys with pelvic dilatation on voiding was associated with ureteric reflux
      grades III or IV. Of the 17 children who did not undergo cysto-urethrography,
      only one had recurrence of urinary infection and was diagnosed with ureteric
      reflux. This girl was one of the three babies who were not scanned during
      voiding. More than half of the infants with febrile urinary infection were
      excluded from invasive examination without having recurrence of urinary
      infection. Thus, ultrasound scanning during voiding was effective for screening
      infants with their first urinary infection to detect significant ureteric reflux.

PMID- 8741316
TI  - Long-term follow up of abdominal aortic aneurysm complicating Kawasaki disease:
      comparison of the effectiveness of different imaging methods.
AB  - A 2 month old boy with Kawasaki disease developed the rare complication of
      abdominal aortic aneurysm (AAA). He was followed up over 7 years by
      ultrasonography (2D-ECHO) with and without Doppler flow evaluation, angiography
      and computed tomography. Calcification was noted 33 months after the onset of the
      disease but the aneurysm did not decrease in size. 2D-ECHO was adequate for
      evaluating the size of an aneurysm, but did not show thrombus formation or
      calcification. Doppler flow studies did not show abnormally high blood flow
      velocities either at the inflow or outlet of aneurysms, which are indicative of
      stenosis. On the other hand an abdominal aortogram provided information regarding
      the luminal shape and abnormalities in flow pattern suggestive of thrombus
      formation. Fluoroscopy cannot demonstrate calcification in the early stages.
      Computed tomography (CT) was the imaging method of choice for the evaluation of
      obstructive or calcific changes; an organizing thrombus was clearly demonstrated
      and early detection of calcification was possible.

PMID- 8741317
TI  - A case of the cardiofacial syndrome (Cayler's syndrome).
AB  - An infant whose face appears asymmetrical at rest and whose mouth is pulled
      downward to one side when crying is said to have an 'asymmetric crying facies'
      (ACF). The association of ACF with congenital cardiac anomalies is known as
      cardiofacial syndrome (Cayler's syndrome). The present report describes a case
      with cardiofacial syndrome and ACF associated other congenital anomalies, and
      provides criteria for differentiating absence of the depressor anguli oris muscle
      (DAOM) from palsy of the seventh cranial nerve and its central connections.

PMID- 8741319
TI  - A newly identified exonic mutation of the WT1 gene in a patient with Denys-Drash
      syndrome.
AB  - An 11 month old boy with hypospadias and bilateral undescended testes developed
      renal failure. Denys-Drash syndrome was suspected and molecular analysis of the
      WT1 gene was performed, although no Wilms' tumor was identified. Direct
      sequencing analysis of genomic DNA from this patient revealed a G to A transition
      resulting in 366Arg to Leu substitution in exon 8 which has hitherto not been
      described. This newly identified mutation will help in the understanding of
      functional domains and in making a diagnosis of Denys-Drash syndrome.

PMID- 8741318
TI  - Improvement of bone disease with increased dose of glucocerebrosidase in a
      Gaucher disease patient who had a bone lesion presenting during low-dose enzyme
      replacement therapy.
AB  - In recent years, enzyme replacement therapy has been shown to be useful for the
      treatment of Gaucher disease. A 10 year old Japanese boy with Gaucher disease
      underwent splenectomy at the age of 5 years and received enzyme replacement
      therapy from the age of 6 years. He had avascular necrosis of the bilateral
      femoral heads, which was not seen at the beginning of the therapy, without
      deterioration of hematological variables during maintenance therapy. The enzyme
      dosage was increased from 20 to 120 IU/kg per month resulting in an improvement
      of the clinical symptoms and bone lesion. In enzyme replacement therapy, dose
      increase is considered to be essential for improvement in bone disease; however,
      it is important to watch for the development of bone lesion.

PMID- 8741320
TI  - Growth hormone deficiency in Dubowitz syndrome.
AB  - Severe short stature as a result of intra-uterine growth retardation is one of
      the characteristics of Dubowitz syndrome. There have been few reports elaborating
      growth hormone secretory status in this syndrome. A child with Dubowitz syndrome,
      who was found to have complete growth hormone (GH) deficiency and who responded
      to growth hormone therapy, is described. This appears to be the first
      documentation of GH deficiency in this syndrome.

PMID- 8741321
TI  - Extensive white matter involvement in hemorrhagic shock and encephalopathy
      syndrome.
AB  - Reported is a case of hemorrhagic shock and encephalopathy syndrome (HSE) with
      extensive white matter involvement. A three year old, previously healthy boy was
      presented with an acute onset of fever, loss of consciousness and convulsions. He
      had disseminated intravascular coagulation, metabolic acidosis, non-ketotic
      hypoglycemia and hepatorenal dysfunction. The computed tomography (CT) scan of
      his head on the second day of illness demonstrated symmetric, extensive low
      density areas in the cerebral and cerebellar white matter. The child died on the
      13th hospital day. A post-mortem histopathological examination of the liver
      revealed centrilobular necrosis and infiltration of fatty acid droplets. The
      concentrations of serum 2',5'-oligoadenylate synthetase and urinary neopterin
      were markedly elevated, indicating excessively activated cell-mediated immunity.
      This overproduction of inflammatory cytokines might play an important role in the
      pathogenesis of the brain lesion as well as in other clinical and laboratory
      manifestations. The patient had a decreased serum level of alpha l-antitrypsin,
      which may have been associated with the development of uncontrolled inflammation
      and coagulation disorder.

PMID- 8741322
TI  - A case of West syndrome with atypical massive gray matter heterotopia that is
      well controlled by ACTH therapy.
AB  - A 4 month old female infant with atypical asymmetrical massive gray matter
      heterotopia diagnosed as West syndrome is described. Her seizure initially
      appeared as afebrile general tonic and clonic convulsion and progressed to
      typical West syndrome consisting of clusters of myoclonic spasms of the
      extremities, mainly on the left side, accompanied by head and eye deviation to
      the right side. Electroencephalogram (EEG) presented typical hypsarrhythmia and
      cranial computerized tomography (CT) and magnetic resonance imaging (MRI) showed
      massive heterotopic gray matter in the right hemisphere with the same density or
      intensity as cortical gray matter. Single photon emission computed tomography
      (SPECT), using N-isopropyl-p-123I-iodoamphetamine (123 I-IMP), demonstrated
      decreased blood flow in the ectopic lesion. Although clinical response to several
      anti-epileptic drugs was poor, her seizures were well controlled by relatively
      low dose adrenocorticotropic hormone (ACTH) therapy of 0.015 mg/kg per day
      followed by a combination of valproic acid and clonazepam.

PMID- 8741323
TI  - Leukophagocytosis in human parvovirus B19-induced transient bicytopenia in a
      healthy child.
AB  - A previously health 11 year old boy had transient leukopenia and thrombocytopenia
      associated with human parvovirus B19 (B19) infection. This case suggested that
      low-grade hemophagocytosis can be involved in developing B19-related cytopenia
      even in an otherwise healthy child. Bone marrow aspiration at an early stage
      could reveal the underlying mechanism of B19-related cytopenia.

PMID- 8741324
TI  - Respiratory failure caused by dual infection with Bordetella pertussis and
      respiratory syncytial virus.
AB  - Two infants with pneumonia caused by both Bordetella pertussis and respiratory
      syncytial virus (RS virus) suffered respiratory failure preceded by convulsion.
      Detection of respiratory pathogens with polymerase chain reaction and enzyme
      linked immunosorbent assay was crucial in the management of dually infected
      infants.

PMID- 8741325
TI  - Acute anterior uveitis in a child with HLA-B60 after Salmonella enteritis
      associated with the transient appearance of auto-antibody.
AB  - A Japanese girl with HLA-B60, but not B27, who developed acute anterior uveitis
      after Salmonella enteritis is described. There was no evidence of arthritis or
      urethritis during this episode. This is the first report that acute anterior
      uveitis after Salmonella enteritis was associated with the transient appearance
      of auto-antibody in the serum at an early period.

PMID- 8741326
TI  - Dyskeratosis congenita: unusual onset with isolated neutropenia at an early age.
AB  - A 3.5 year old male patient with dyskeratosis congenita (DC) presented at the age
      of 13 months with isolated neutropenia preceding characteristic skin findings.
      The average absolute neutrophil count of 500/mm3 persisted without the presence
      of anemia or thrombocytopenia during the follow up. Neutropenia responded to
      granulocyte-colony stimulating factor (G-CSF) at a dose of 10 micrograms/kg per
      day. Immunologic findings were normal as was the chromosomal stability and sister
      chromatid exchange.

PMID- 8741327
TI  - Masked ureteral duplication with ectopic ureter detected by magnetic resonance
      imaging.
AB  - The usefulness of magnetic resonance imaging (MRI) in the detection of a masked
      duplex kidney system is described. A 9 year old girl was admitted to our hospital
      for urinary incontinence. She was found to possess an ectopic ureter associated
      with complete ureteral duplication. She had been evaluated for incontinence at
      several hospitals, but neither ultrasound sonography nor intravenous pyelography
      detected any abnormalities. Only cystoscopic examination and MRI detected the
      anomalies. Partial nephroureterectomy resolved the patient's incontinence. MRI is
      useful for the detection of ureteral duplication and should be used on cases in
      which this condition is suspected, prior to performing invasive procedures.

PMID- 8741328
TI  - Anti-verocytotoxin (VT)1, VT2 and VT2c antibodies in commercial intravenous
      immune globulins in Japan.

PMID- 8741329
TI  - [Pharmacokinetics and its methods of investigation].

PMID- 8741330
TI  - [Studies on transcranial magnetic stimulation--Part 2. Pathological findings of
      rabbit brain after long-term stimulation based on characteristics of
      intracerebral induced voltage].
AB  - I investigated the safety of transcranial magnetic stimulation (TMS) with a
      double coil. Induced voltages of a double coil compared in rabbit brain with
      those in the atmosphere were almost equal. When the distance from the coil's
      surface was disregarded, the maximum induced voltage spot did not move. Based on
      these characteristics of a double coil, the safety of TMS was examined in rabbit
      brain and brainstem tissues using high magnetic pulses (2.4 tesla) and high
      frequencies (100 approximately 200 stimuli per day, total of 5,000 stimuli), over
      a long-term period (30 approximately 42 days). Under these conditions, the brain
      and brainstem tissues showed no abnormal lesions. In conclusion, I suggest that
      TMS with a double coil does not influence the brain tissues such as the visual
      conduction system and the ocular motor system, under the above conditions.

PMID- 8741331
TI  - [A study of acute infection of herpes simplex virus in mouse trigeminal ganglia].
AB  - We investigated the shift to latency and protective reaction in mice trigeminal
      ganglia after inoculation of herpes simplex virus type 1 (HSV-1) onto the cornea.
      BALB/c mice were inoculated and the trigeminal ganglia were removed periodically.
      Lymphocytes in the ganglia were observed using immunocytochemical techniques. The
      results obtained were as follows: (1) HSV-1 positive neuronal cells were
      recognized at 3 days after inoculation but not at 14 days. (2) The relative
      proportion of T cells in lymphocytes was greater than that of B cells at 3 days,
      but B cells were more numerous at 5 days. Then T cells become more numerous again
      at 7 days. (3) Among the subsets in T cells, the ratio of CD4+ and CD8+ cells was
      almost equal at 3 days, but then CD4+ cells increased and CD8+ cells had
      disappeared at 14 days after inoculation. These results show that HSV-1 that
      reached the trigeminal ganglion from the cornea by axonal transport infected
      neuronal cells, multiplied there and then disappeared resulting in latency.
      Cellular immunity, especially the function of CD4+ cells, played a main role in
      this protective reaction by suppressing the viral growth.

PMID- 8741332
TI  - [Production and metabolism of prostaglandin D2 by cultured chick retinal pigment
      epithelial cells].
AB  - The production and metabolism of prostaglandin (PG) D2 in cultured chick retinal
      pigment epithelial (RPE) cells were studied. The production of PGD2 was evaluated
      using thin layer chromatography (TLC) after labeling the RPE cells with 1
      14Carachidonic acid (AA) and radioimmunoassay (RIA). The metabolism was evaluated
      by measuring the activity of 15-hydroxyprostaglandin dehydrogenase. The
      conversion of AA to PGD2 was detected by TLC, and this conversion was inhibited
      with indomethacin (10(-5)M). In a steady state, 198 +/- 50 pg/6 x 10(5) cells/2
      hours of PGD2 was detected by RIA. The amount of PGD2 was greater than that of
      both PGE2 and PGF2 alpha. The nicotinamide adenine dinucleotide phosphate (NADP)
      linked 15-hydroxyprostaglandin dehydrogenase activity was detected in the 10,000
      g supernatant of the RPE cells. These results demonstrated that cultured chick
      RPE cells produce and metabolize PGD2.

PMID- 8741333
TI  - [A monkey chair specially designed for ophthalmic examinations and intraocular
      pressure measurement in the conscious cynomolgus monkey].
AB  - We constructed a monkey chair specially designed for ophthalmic examinations such
      as biomicroscopic examination, applanation tonometry etc. It was made of
      stainless steel and acrylic plastic, equipped with a protection plate for the
      experimenter, and adjustable to the size of the monkey. Using this chair,
      intraocular pressure (IOP) measurements of a fully conscious cynomolgus monkey
      were carried out at intervals of one or two hours from 10:00 AM to 10:00 PM. The
      IOP, at 6:00, 8:00 or 10:00 PM was compared with the IOP measured at the same
      time of the day after one or two weeks. The IOP while fully conscious showed
      diurnal variation (p < 0.001, ANOVA). The IOP measured at the same time of the
      day at one or two week intervals showed reasonable reproducibility.

PMID- 8741334
TI  - [Pharmacokinetics of norfloxacin and lomefloxacin in aqueous humour analysed by
      microdialysis].
AB  - The pharmacokinetics of norfloxacin (NFLX) and lomefloxacin (LFLX) in rabbit
      aqueous humour after instillation of 0.3% solution (20 microliters) and oral
      administration (20 mg/kg) were investigated by microdialysis. We also measured
      plasma concentration of fluoroquinolones after oral administration. After
      instillation, the maximum concentration (Cmax) of NFLX and LFLX in the aqueous
      humour was 0.80 and 1.20 micrograms/ml, and elimination half time (t1/2) was 130
      and 96 min, respectively. After oral administration, the Cmax in plasma of NFLX
      and LFLX was 2.06 and 1.89 micrograms/ml, and the Cmax in aqueous humour was 0.16
      and 0.62 microgram/ml, respectively. t1/2 of NFLX in aqueous humour and plasma
      was 225 and 295 min, and t1/2 of LFLX was 188 and 175 min, respectively. The
      ratio of aqueous humour/serum concentration of NFLX and LFLX was 7.8 and 35.3% 4
      hrs after oral administration. These results suggest that, after instillation,
      LFLX penetrated better into the aqueous humour, and was eliminated faster, than
      NFLX, and that after oral administration, NFLX could not panetrate well into the
      aqueous humor from the blood.

PMID- 8741335
TI  - [Corneal distortion induced by speculum--studies with computer-assisted corneal
      topography].
AB  - The corneal distortion induced by the presence of an eyelid speculum was analysed
      by the Videokeratoscope-Eyesys Corneal Analysis System (EYESYS), with a Barraquer
      type speculum (B group) in 22 normal eyes and with a Kratz-Barraquer type
      speculum in 38 normal eyes (KB group). The following differences were evaluated
      in the 2 groups: intraocular pressure (IOP), refractive power, change in
      astigmatism of the Cravy method, and corneal refractive power before and after
      the specula were put in the interpalpebral fissure. Significant differences were
      found in the IOP in the KB group, in spherical equivalent in the B and KB groups,
      and in corneal refractive power in the B groups. Then the 38 eyes of the KB group
      were divided into two groups by the average level of proptosis and the average
      difference of IOP, and the corneal refractive power of the two groups was
      compared by statistical analysis. Significant difference was found in the
      direction of 0 degree/ 180 degrees in the group with higher than average
      proptosis and in the direction of 90 degrees/ 270 degrees in the group with
      higher than average difference in IOP. Multiple regression analysis suggested
      that higher grades of proptosis were related with steeper vertical meridians and
      that wider palpebral fissures were associated with steeper horizontal meridians.
      Multiple regression also showed that the speculum did not cause corneal
      distortion with the proper relation between level of proptosis and width of the
      palpebral fissure.

PMID- 8741336
TI  - [Effects of topical application of isopropyl unoprostone on refraction and
      accommodation].
AB  - The effect of topical application of prostaglandin-related compound isopropyl
      unoprostone on refraction and accommodation were examined. Topical application of
      isopropyl unoprostone obviously reduced the intraocular pressure, but no
      significant change in refraction was observed. Amplitude of accommodation, i.e.,
      near point and far point of accommodation, were kept unchanged, although
      isopropyl unoprostone produced a slight hyperopic shift in dark focus of
      accommodation. These findings suggest that the reduction of intraocular pressure
      needs to be explained by a mechanism other than the relaxation of ciliary
      muscles.

PMID- 8741337
TI  - [Effects on visual functions following several hours' usage of a head mounted
      display].
AB  - We investigated the effects of viewing video movies with a head-mounted display
      (HMD) for 4 to 6 hours on visual functions such as refraction, visual acuity, and
      accommodation-vergence system. Two or three video movies were watched without any
      breaks by 13 normal volunteers (age: 22 approximately 40). Measurements were made
      of (1) objective and subjective refraction, (2) corrected visual acuity, (3)
      tonic level and step response of accommodation with a computer-assisted infrared
      optometer, and (4) near and far phorias and AC/A ratio. Significant transient
      myopia was found following 4 hours' viewing, but not following 6 hours' viewing.
      Scrutinizing individual data, myopia was consistently found in some subjects, and
      hyperopia in others. We presumed that many subjects might have been influenced by
      initial instrumental myopia when they adjusted the focus by using the mechanism
      built in the HMD. No significant change was observed in any other examination.
      However, there was a tendency for the AC/A ratio to change after a short time,
      and then to recover to its original value. Based on the results in this study, it
      appears that some changes in accommodation and vergence systems are caused by
      viewing video movies with the HMD. Although the amount of changes was within
      normal physiological variation in this study, the possibility still remains that
      usage for a longer time may lead to other changes in visual function. Care is
      also necessary when using the HMD in subjects with subclinical problems.

PMID- 8741338
TI  - [Functional magnetic resonance imaging of the frontal eye fields during saccadic
      eye movements].
AB  - We evaluated activity-induced signal intensity changes in the human cerebral
      cortex during horizontal saccadic eye movements using functional magnetic
      resonance imaging (fMRI) based on the blood-oxygenation-level-dependent (BOLD)
      contrast method. Compared with central fixation, significant signal increases
      were observed bilaterally in the middle frontal gyrus (Brodmann area 8) during
      saccadic conditions. The location of the activated area was consistent with that
      of previously reported frontal eye fields (FEF). These results suggest that fMRI
      has potential merit for the study of cortical control of eye movements in humans.

PMID- 8741339
TI  - [Anterior chamber dimensions in patients with angle-closure glaucoma measured by
      an anterior eye segment analysis system].
AB  - The corneal curvatures, iridocorneal angles, anterior chamber depths, and
      anterior chamber volumes in 26 (5 male and 21 female) patients with primary angle
      closure glaucoma were measured using an anterior eye segment analysis system (EAS
      1000, Nidek). The radius of corneal curvature was 7.65 +/- 0.25 mm (mean +/-
      standard deviation), significantly smaller than age-matched controls, and the
      iridocorneal angles ranged between 19 and 21 degrees. The anterior chamber depth
      and volume of angle-closure glaucoma eyes did not correlate with age; the depth
      averaged 1.90 +/- 0.41 mm, and the volume averaged 83.3 +/- 28.4 microliters.

PMID- 8741340
TI  - [Application of oculokinetic perimetry in examination of the eye].
AB  - Oculokinetic perimetry was performed using the same protocol at four health
      screening facilities to determine its usefulness for identifying visual field
      abnormalities including glaucoma during complete physical screenings in Japan.
      Ophthalmoscopy of the optic disc, 26-point oculokinetic perimetry (OKP), and
      applanation tonometry were performed in 2,768 eyes. If any one of the tests
      yielded an abnormal result, the eye was then examined with a Humphrey visual
      field analyzer (HVFA, program 30-2). After the tests were completed, the results
      were evaluated by ophthalmologists for evidence of primary open-angle glaucoma
      and normal tension glaucoma and were classified into one of 3 groups: confirmed
      glaucoma, suspected glaucoma, and no glaucoma. OKP detected abnormalities in the
      visual field in 96 eyes (3.5%). Of these 96 eyes, 29 eyes had confirmed glaucoma,
      52 eyes were suspected of having glaucoma and 15 eyes had no glaucoma. The
      remaining 15 eyes had no glaucoma, but in 7 of them other ophthalmological
      disease was diagnosed. The sensitivity, specificity, positive predictive value,
      and negative predictive value of OKP for detecting glaucomatous visual field
      defect were 0.46, 0.99, 0.84 and 0.96, respectively. The high specificity and
      negative predictive value show that OKP is unlikely to produce false positive
      results, but its low sensitivity suggests that it is not suitable for the early
      detection of glaucoma. However, OKP identified advanced glaucoma and other
      ophthalmological diseases associated with visual field abnormalities, suggesting
      that it is a useful screening test.

PMID- 8741341
TI  - [The Hanshin-Awaji earthquake and the recurrence of endogenous uveitis].
AB  - The recurrence mechanism of endogenous uveitis remains to be explained, but it is
      popularly believed that hereditary background and environmental changes affect
      this mechanism. On Jan 17, 1995, the Hanshin-Awaji distinct in Japan was struck
      by a major earthquake. Over 6,300 people were killed and more than 310,000 were
      made homeless. The inhabitants of this area suffered emotional stress from the
      sudden changes in their living environment. In 116 endogenous uveitis patients
      who were being followed up for more than 2 years after Jul 17, 1993, at Kobe
      University Hospital in the stricken area, we investigated the recurrence rate of
      endogenous uveitis before and after the earthquake. The recurrence rate after the
      earthquake was significantly higher than before the earthquake (10% vs 3%), and
      women were more often affected than men after the earthquake. Our data suggests
      that psychological stress from sudden changes in the living environment after the
      earthquake can trigger the recurrence of endogenous uveitis. It might be
      important to provide psychological as well as physical care of endogenous uveitis
      patients after a disaster.

PMID- 8741342
TI  - [A special form of Stargardt's disease/fundus flavimaculatus].
AB  - Stargardt's disease is a bull's-eye macular dystrophy with the characteristic
      appearance of a perifoveal lesion. We have observed four cases of an autosomal
      recessive disease with fundus features undistinguishable from Stargardt's
      disease, but with a different nature and much poorer prognosis. One case typical
      of Stargardt's disease characterized with macular degeneration showed a bull's
      eye with dark choroid. Sixteen years later, the same eye developed bone corpuscle
      pigmentation in the periphery with non-recordable electroretinogram. The other
      three cases were members of a single family. They showed typical macular
      degeneration consistent with Stargardt's disease but had peripheral degeneration
      as well. Taking into account that there is a great diversity of retinal functions
      in Stargardt's disease, these features are different from those reported
      previously. Stargardt's disease should not be considered as a single clinical
      entity with a fair prognosis.

PMID- 8741343
TI  - [Adhalin gene mutations in malignant limb-girdle muscular dystrophy and clinical
      features in adhalin-deficient muscular dystrophy].
AB  - We have reported adhalin gene mutations in 4 patients from 3 families with
      malignant limb-girdle muscular dystrophy (MLGMD), and summarized the clinical
      features in adhalin-deficient muscular dystrophy (ADMD) reported as severe
      childhood autosomal recessive muscular dystrophy (SCARMD) in the English
      literatures. Adhalin cDNA amplified from RNA by reverse transcription polymerase
      chain reaction (RT-PCR) was sequenced in 3 patients from 2 consanguinous families
      (Wa. and Ta.) with MLGMD who showed immunohistochemically a complete deficiency
      of adhalin in the skeletal muscle, and adhalin genomic DNA amplified by PCR was
      sequenced in 1 patient from a non-consanguinous family (Ma.). In one patient from
      family Wa., a cytosine to thymine substitution at nt. 229 was identified in the
      adhalin gene, resulting in the replacement of Arg by Cys at codon 77. In two
      patients from family Ta., an adenine to guanine substitution at nt. 410 and an
      insertion of 15 bases between nt. 408 and 409 were identified, resulting in Glu
      to Gly replacement at codon 137 and insertion of a peptide with 5 amino acids. In
      one patient from family Ma., a deletion of adenine at nt. 404 or nt. 405 and a
      thymidine to cytosine substitution at nt. 470 were identified. These amino acid
      replacements are expected to change the secondary and tertiary structure, which
      may affect the interaction of adhalin with other dystrophin-associated
      glycoproteins and basal lamina, and may subsequently cause the degeneration of
      muscle fibers. Sixty-six cases from 49 families with ADMD have been reported in
      the literature. Compared with patients with Duchenne muscular dystrophy (DMD),
      patients with ADMD were older in age at the time of onset or loss of ambulation.
      Mental retardation and cardiac dysfunction were rarely observed in ADMD patients.
      On muscle histology, the number of necrotic fibers, opaque fibers and
      regenerative fibers was less in ADMD. ADMD was classified into two groups;
      complete and incomplete adhalin-deficient. There was no essential difference
      between the two groups in clinical features and muscle histology, but the former
      was characterized by more severe clinical features than the latter. ADMD can be
      caused by various types of mutations in the adhalin gene.

PMID- 8741344
TI  - [Peptidergic sweating in multiple system atrophy and hereditary spinocerebellar
      ataxia with special reference to calcitonin gene-related peptide].
AB  - Calcitonin gene-related peptide (CGRP)-like immunoreactivity has been
      demonstrated to be present in nerve terminals around the sweat glands. We have
      previously demonstrated that CGRP modulates the cholinergic sweating activity.
      The present study was designed to evaluate the locally administrated CGRP on
      sweating of patients with multiple system atrophy (MSA) and hereditary
      spinocerebellar ataxia (HSCA) consisting of 10 males and 11 females. Among 9
      HSCA, 3 was diagnosed as Machado-Joseph disease by clinical and DNA diagnostic
      assessment. CGRP and methacholine chloride (MCH) was dissolved in saline solution
      to specified concentration, and 0.1ml of which was injected intradermally at the
      center of a forearm test area. The sweat rate was recorded continuously by the
      capacitance hygrometry in a relatively cool environment in which the spontaneous
      sweating was absent. CGRP significantly increased the sweat rate when it was
      administrated with MCH on normal subjects. There was a clear dose-dependent
      relationship between the dose of CGRP and its enhancement. This enhancement was
      significantly reduced in patients with MSA as compared with controls. On the
      other hand, most of HSCA showed no remarkable impairment of CGRP enhancement.
      These results suggest that peptidergic sweating is extensively affected in
      patients with MSA but is not in patients with HSCA, which may be the consequence
      of peptidergic sweating dysfunction in MSA.

PMID- 8741345
TI  - [Diagnosis of intracardiac thrombi by various imaging techniques and activation
      of platelets and coagulation-fibrinolysis in patients with cardioembolic stroke].
AB  - Recent epidemiological studies have suggested that 15 to 30% of all ischemic
      stroke is comprised of cardioembolic stroke. The presence of intracardiac thrombi
      might prove to be the most reliable tool when making a diagnosis of cardioembolic
      stroke, although not always easy to determine even with recent advanced
      technique. In this study, sensitivities to detect intracardiac thrombi of
      transthoracic echocardiography (TTE), transesophageal echocardiography (TEE),
      cardiac-enhanced CT (CCT) and scintigraphy with indium-111-tropolone-labelled
      platelets (PSG) were compared, in order to provide a relevant guideline for the
      diagnosis of intracardiac thrombi in 83 patients suspected of cardioembolic
      stroke. Also studied was the correlation of intracardiac thrombi with activation
      of platelets and coagulation-fibrinolysis through performing various hemostatic
      tests in order to investigate their utility for the evaluation of in situ
      thrombosis or prothrombotic state in the heart chamber. Detection rates of
      intracardiac thrombi were 35% in TEE, 26% in CCT, 19% in PSG, and 11% in TTE.
      There was a significant difference in the sensitivity between TEE and TTE (p <
      0.05). Left atrial thrombi were frequently detected in TEE (4 out of 5 patients)
      and CCT (7 out of 10), while they were found less in PSG (2 out of 4) an TTE (4
      out of 10). Thrombi in the left appendage were visualized in 3 out of 3 by TEE,
      while only in 1 out of 3 by PSG, 1 out of 4 by TTE and 1 out of 4 by CCT. Left
      ventricular thrombi; CCT (3 out of 3), TTE (2 out of 3), PSG (1 out of 1); TEE
      was not performed since this technique could not be expected to provide high
      quality images of left ventricular thrombi. Thus, left atrial thrombi were
      considered to be more sensitively detected by TEE and CCT, left appendage thrombi
      by TEE, and left ventricular thrombi by TTE and CCT. There was no patient in whom
      an intracardiac thrombus was visualized by PSG alone. On the basis of the results
      above, we propose the following guideline for the detection of intracardiac
      thrombi in patients presented with cardioembolic stroke. First, TTE and CCT
      appear to be relevant for screening tests because of simple and non-invasive
      techniques. These two tools might be sensitive enough to find left ventricular
      thrombi. Second, TEE should be recommended when a thrombus is suspected in the
      left atrium or appendage. Finally, PSG may be used to determine the activity of
      the thrombus, according to its necessity. Among the patients having intracardiac
      thrombi, frequently observed was the increase of beta-thromboglobulin, platelet
      factor 4, platelet lysis, thrombin-antithrombin III complex, D-dimer in 67%, 75%,
      71%, 80% and 80%, respectively, as well as the shortening of platelet survival in
      100%, while anrithrombin III was reduced in only 38%. In addition, when
      hemostatic abnormalities were compared between positive and negative groups of
      intracardiac thrombi, the shortening of platelet survival (p < 0.0001), the
      increase of platelet lysis, and the increase of D-dimer (p < 0.04) were more
      frequent in the positive group than in the negative group. These results indicate
      that the findings of activation of platelets and coagulation-fibrinolysis, except
      for the reduction of antithrombin III, especially the findings of platelet
      consumption and lysis as well as fibrinolysis activation are useful as sensitive
      parameters of in situ thrombosis or prothrombotic state, which may lead to the
      formation of intracardiac thrombi.

PMID- 8741346
TI  - [Familial amyloidosis, Finnish type with marked anhidrosis].
AB  - Familial amyloidosis, Finnish type (FAF), is a gelsolin-related systemic
      amyloidosis that has an autosomal-dominant inheritance pattern and is clinically
      characterized by progressive cranial neuropathy, corneal lattice dystrophy and
      skin changes such as cutis laxa, blepharochalasis, and lichen amyloidosis. A 70
      year-old Japanese male proband, who was believed to be originally from Fukuoka
      Prefecture, showed signs and symptoms characteristic of FAF. In addition, he
      complained of progressive anhidrosis and heat intolerance during the daytime in
      summer. On examination, perspiration was absent on the almost entire body
      surface. Molecular genetic studies showed a G-to-A transversion that resulted in
      the substitution of asparagine for aspartic acid 187 in the gelsolin gene, a
      mutation found in most patients with FAF. Skin biopsy revealed marked deposition
      of amyloid, which was positive with anti-gelsolin antibody staining, around
      eccrine sweat glands and ducts, and around sebaceous glands, outside the basal
      lamina; slight to mild deposition around small vessels and small nerve fascicles;
      and very slight deposition in the perineurium and endoneurium. Morphometric
      evaluation of the nerve terminals and axons of eccrine sweat glands revealed a
      significant decrease in the number of nerve terminals per transverse profile of
      the sweat gland. Compared with controls, nerve terminals were further from the
      secretory epithelial cell owing to deposition of amyloid outside its basal
      lamina. The proband's sister had almost identical, although much less severe,
      clinical signs and symptoms with the same mutation of the gelsolin gene.
      Autonomic signs and symptoms in FAF are reported to be less frequent and less
      severe than those in familial amyloid polyneuropathy of Andrade type. Findings in
      our proband suggest that perspiration may be markedly decreased in FAF owing to
      marked deposition of amyloid around the eccrine sweat gland which causes
      degeneration of the nerve terminals and disturbs access of the neurotransmitter
      to the secretory epithelial cell.

PMID- 8741347
TI  - [Diffusion MRI study of cerebral white matter lesions in patients with
      Binswanger's disease].
AB  - We performed diffusion MRI studies in 14 patients with extensive ischemic
      leukoencephalopathy, including 9 with dementia (diagnosed as Binswanger's
      disease), and 5 without dementia, and 8 age-matched controls. Apparent diffusion
      coefficients (ADCs) in anterior and posterior periventricular white matter were
      significantly higher in demented and non-demented patients than in the controls,
      and diffusion anisotropy disappeared in patients because of the high ratio of the
      diffusion coefficients perpendicular to the nerve fibers to those parallel to the
      nerve fibers. ADCs in the corpus callosum were significantly higher in demented
      patients that in non-demented patients and controls. Therefore, diffusion
      anisotropy disappeared only in demented (Binswanger's disease) patients. These
      results suggest that the cerebral white matter lesions in Binswanger's disease
      reflect a decrease of nerve fibers and diffuse myelin loss, and that the loss of
      nerve fibers in the corpus callosum may play a role in inducing cognitive
      decline. Diffusion MRI may be useful in the pathophysiological evaluation of
      cerebral white matter lesions.

PMID- 8741348
TI  - [Identification of neuronal death and DNA fragmentation in early stage after rat
      transient forebrain ischemia].
AB  - To clarify whether programmed cell death plays an important role in the delayed
      neuronal death after forebrain transient ischemia, we investigated the
      relationship between pathological changes visualized by HE staining and
      intranuclear DNA fragmentation evaluated by the TUNEL method in rat hippocampal
      CA1 pyramidal neurons at early times after the onset of transient forebrain
      ischemia. The investigations were carried out in male Wistar rats (N = 22)
      subjected to 20 minutes of transient forebrain ischemia by Pulsinelli's method.
      No morphological changes or TUNEL staining were observed at 1 hour after
      forebrain ischemia. HE staining revealed morphological changes in 8 +/- 4%, 10 +/
      4% and 88 +/- 9% of neurons in hippocampus CA1 at 3, 6 and 24 hours after
      forebrain ischemia, respectively at which times 0%, 74 +/- 1% and 68 +/- 11% of
      the neurons showed marked labeling with the TUNEL method. We therefore conclude
      that DNA fragmentation as evaluated by the TUNEL method is not involved in
      neuronal death, and no DNA fragmentation was detectable prior to morphological
      changes in the early stage of forebrain ischemia.

PMID- 8741349
TI  - [Preserved implicit reading and the recovery of explicit reading in a pure
      alexic].
AB  - We described a 55-year-old, right-handed, university-educated Japanese man who
      showed pure alexia after an infarction in the territory of the left posterior
      cerebral artery. Damage to the corpus callosum was limited to the most caudal
      part of the splenium. In the early days of his illness, he demonstrated the
      inability to read aloud on either Kana (Japanese syllabograms) or Kanji (Japanese
      morphograms). In contrast, he could semantically categorize Kanji-words such as
      animals or non-animals. Subsequently, he gradually regained the ability of
      reading aloud Kanji as well as Kana. At that time, we further investigated the
      relation between his reading ability and the attributes of 881 Kanji characters
      including hieroglyphicity, concreteness, and familiarity. We found that he could
      more readily read Kanjis with higher hieroglyphicity, concreteness, and
      familiarity. The reading times for Kanji-words were significantly shorter than
      those of corresponding Kana-words. Moreover, he showed some difficulty to read
      Kana-words and Kana combinations without meaning when asked to perform repetitive
      opposing movements with his thumb and little finger inhibiting kinesthetic
      reading. The effect was not observed when he read Kanji-words. These results lead
      us to suggest the following: (1) the two components of reading, reading aloud and
      comprehension abilities, are dissociable in a pure alexic, especially in Kanji
      reading; and (2) recovery mechanisms underlying Kanji and Kana reading were
      different in our case. Namely, restitution of the direct connection through the
      residual splenium fibers between the visual word form processing area in the
      right hemisphere and the left angular gyrus was attributed to Kanji reading, and
      utilization of kinesthetic reading played an important role in Kana reading.

PMID- 8741350
TI  - [A family with X-linked hydrocephalus resulting from mutations in the neural cell
      adhesion molecule L1].
AB  - We present the two siblings with X-linked hydrocephalus (XLH) and discuss the
      clinical features and genetical analysis of them. Case 1. The proband, a male,
      was delivered by the emergency cesarean section because of enlarged head
      circumference (44cm). His head circumference at 24 years old was 92cm.
      Neurological examination revealed adducted thumbs, horizontal nystagmus,
      hyperreflexia and spasticity of legs. He had tonic convulsions. MRI revealed a
      very thin layer of cerebral cortex. Molecular analysis revealed a deletion of 5
      bases in exon 8 of the cell adhesion molecule L1 (L1CAM) gene located at
      chromosome Xq28. Case 2. The younger maternal half brother of case 1 was also
      born by the cesarean section, with 48cm in head circumference. A ventriculoatrial
      shunt was placed at the first month old. Epileptic seizures were seen. At the age
      of 21 years he had a head circumference of 59cm. A physical examination showed
      bilateral adducted thumbs, upward deviation of eyes, hyperreflexia and spasticity
      of legs. CT showed marked generalized ventricular enlargement including the
      fourth ventricle. Molecular analysis confirmed the same mutations as that of case
      1. A maternal uncle had a previous diagnosis of hydrocephalus, and a sister is
      identified as a heterozygous carrier from molecular genetical analysis. Our
      results indicate that HLX is caused by the mutations in the gene for neural L1CAM
      in our family.

PMID- 8741351
TI  - [A case of conus syndrome following arteriogenic impotence].
AB  - A patient with conus syndrome following arteriogenic impotence is described. A 62
      year-old man became impotent. 7 months after the onset, he was admitted because
      of a sudden left sensorimotor disturbance (L2 to S5 segments) when he awoke. A
      marked bilateral reduction of cutaneous sensation in the S2 to S5 dermatome
      distribution persisted. An MRI of the spinal cord demonstrated no abnormal lesion
      on T2-weighted and Gadolinium enhanced images. Angiography of the pelvic artery
      showed severe arteriosclerotic findings. We diagnosed this case as a conus
      syndrome due to ischemia in the conus medullaris. The impotence in our case was
      considered to be arteriogenic because there was no detection of the bilateral
      deep arteries of the penis on angiography after an intracorporeal PGE1 injection.
      In this case, arteriogenic impotence might be a prodrome of a conus medullaris
      infarction.

PMID- 8741352
TI  - [A case of Kennedy-Alter-Sung (KAS) syndrome presenting as hypersexuality and
      elevated serum CK: usefulness of genetic analysis].
AB  - We report a unique case of KAS syndrome presenting as hypersexuality and elevated
      serum creatine kinase (CK). None of the other members of the patient's family had
      KAS. The patient had engaged in sexual behavior 4 approximately 5 times a week
      since his marriage. He did not have gynecomastia or hepatomegaly. Neurological
      examination revealed facial twitching and tongue atrophy and fasciculations. Mild
      to moderate muscular atrophy and weakness were evident in the proximal portion of
      the upper and the distal portion of the lower extremities. Deep tendon reflexes
      were absent, as were sensory disturbance and sphincter dysfunction. Laboratory
      data showed mild elevation of transaminase (GOT 113 U/L, GPT 69 U/L) and extreme
      elevation of CK (4,600 U/L) in serum. Electromyography and muscle biopsy from the
      left biceps showed chronic neurogenic atrophy. Genetic analysis showed increased
      expansion of a CAG repeat (44 repeats) in exon 1 of the androgen receptor gene.
      We diagnosed KAS syndrome based on the genetic analysis. This case is important
      in illustrating the clinical varieties of KAS syndrome, as well as the importance
      of genetic analysis in KAS syndrome cases presenting with atypical manifestations
      and without a family history.

PMID- 8741353
TI  - [Early diagnosis of herpes simplex virus encephalitis by single photon emission
      computed tomography (SPECT) in patients with normal MRI].
AB  - Since treatment of herpes simplex virus encephalitis (HSVE) is most effective
      when started early, a sensitive and specific method for early diagnosis would be
      of great benefit. MRI and CT are commonly used for this purpose. In this study,
      we presented two patients who had serologically confirmed HSVE and had normal CT
      and MRI, but were diagnosed as having HSVE by means of SPECT in the early stage.
      Case 1 was a 56-year-old man who suddenly developed alexia. On admission,
      physical and neurological examination were unremarkable except for alexia,
      agraphia, acalculia, and left-right disorientation. Brain CT, MRI, and cerebral
      angiography were all normal. However, SPECT showed hyperaccumulation of 99m Tc-HM
      PAO in the right temporal-occipital area. On the 5th hospital day, he became
      comatose. CSF study revealed marked pleocytosis. Even then, MRI including Gd
      enhanced study was normal while SPECT continued to show hyperaccumulation.
      Detection of herpes simplex virus DNA in CSF by polymerase chain reaction was
      negative. Anti-HSV antibody titer in CSF and serum confirmed intrathecal
      production of the antibody on the 14th hospital day. Abnormal accumulation of
      tracer in SPECT returned to normal on the 31st day when he was alert but still
      had a mild Gerstman syndrome. Case 2 was a 61-year-old man with disturbance of
      consciousness, mental dysfunction, and generalized convulsion. He was diagnosed
      as having HSVE by means of CSF pleocytosis, detection of HSV DNA in CSF by
      polymerase chain reaction, and presence of anti-HSV antibody in the CSF. CT and
      MRI again revealed no abnormality while SPECT clearly showed hyperaccumulation in
      the left temporal lobe in an early stage. Hyperaccumulation of lipophilic tracer
      on SPECT study, especially in the temporal lobes, has been reported in the early
      stage of HSVE by previous investigators. Unlike MRI or enhanced CT, the increased
      tracer accumulation in SPECT does not reflect disruption of the blood-brain
      barrier or inflammatory edema, but reflects hyperperfusion or some other HSVE
      related abnormality which is currently unknown. From these observations, we
      suggest that local hyperperfusion occurs before local inflammation, and that
      SPECT is the most useful scanning method for early diagnosis of HSVE when this
      disease is clinically suspected.

PMID- 8741354
TI  - [Monocular photopsia preceding with neovascular glaucoma due to internal carotid
      artery occlusion; a case report].
AB  - We described a 67-year-old right handed man with a left internal carotid artery
      occlusion, who developed monocular photopsia that supervened neovascular
      glaucoma. He had an antecedent transient motor aphasia. His photopsia,
      exaggerated by light, persisted intermittently. Orbital bruit was obtained on the
      left, more clearly during the photopsia. Brain MRI, cerebral angiography, and
      duplex sonography of carotid and ophthalmic arteries indicated left internal
      carotid artery (ICA) occlusion with collateral circulation through the ophthalmic
      artery. Visual evoked potentials (VEPs) revealed a prechiasmal disturbance of the
      optic pathway of the left side. The patient had carotid endarterectomy of the
      left ICA, and his visual disturbance has gradually improved. Ocular symptoms due
      to ICA ischemia are commonly transient visual loss with dark background known as
      amaurosis fugax. Neovascular glaucoma is sometimes complicated with carotid
      artery occlusion. However, photopsia associated with carotid artery occlusion is
      rare. Photopsia mimics scintillating scotomata, but the latter precedes migraine
      and is biocular and homonymous, ascribable to spreading depression from the
      occipital lobe. Retinal or prechiasmal optic pathway might be influenced by poor
      circulation of the ophthalmic artery. In addition, disturbance of light
      adaptation due to retinal hypoperfusion may be possible reason. Neovascular
      glaucoma is intractable, once developed. Therefore, atypical scintillating visual
      disturbance must be recognized as a sign of carotid artery insufficiency and
      supervened glaucoma to prevent it.

PMID- 8741355
TI  - [Familial amyotrophic lateral sclerosis showing variable clinical courses with
      (Leu84-->Val) mutation of Cu/Zn superoxide dismutase].
AB  - A family with autosomal-dominant amyotrophic lateral sclerosis with
      histopathological confirmation on autopsy was described. A 42-year-old female
      proband showed the signs and symptoms only in the lower limbs characteristic of
      lower motor neuron involvement at the onset. ALS had been diagnosed in other five
      members in three generations of her family. The mean +/- SD age of onset of the
      disease was 42.5 +/- 9.3 years with a range of 30 to 51 years. The mean +/- SD
      duration of the disease (n = 5, excluding the proband) was 56 +/- 70 months with
      a range of 7 to 180 months. Molecular genetic studies showed a T-to-G
      transversion that results in the substitution of valine for leucine84 in exon 4
      of the Cu/Zn superoxide dismutase (SOD) gene on chromosome 21 in a proband. This
      mutation is identical to that found in the Japanese family with autosomal
      dominant ALS characterized by short duration of the disease, within 1.5 years, in
      all the affected family members. Therefore, the clinical phenotype, especially
      the duration of the disease seems to be highly variable even in the families with
      the identical mutation of the Cu/Zn SOD gene.

PMID- 8741356
TI  - [An analysis of A-wave with slowed conduction in its afferent and efferent
      pathways below the branching point].
AB  - Motor nerve conduction study was carried out in a 59-year-old woman with 20
      years' history of diabetes mellitus. When her right ulnar nerve was stimulated at
      the wrist, the needle electrode penetrated into the first dorsal interosseous
      muscle revealed an existence of A-wave. Following characteristics were observed:
      (1) A-wave appeared with more than 20 mA of the stimuli, in a all-or-none manner
      at the latency of 54 msec; (2) when stimulated more than 50 mA, A-wave jumped at
      10 msec of the latency and were superimposed upon the M-wave; (3) A-wave had a
      stable latency; (4) when stimulated at the more proximal site, A-wave had longer
      latency (direct pathway) by strong stimuli, and the potential had shorter latency
      (indirect pathway) by weak stimuli; and (5) A-wave was not collided by paired
      stimuli. A-wave conduction velocity was slower than 10 m/sec in the distal part
      of the reflecting point both in afferent and efferent pathways. This report is
      the first to show strikingly slowed conduction of A-wave distal to the reflecting
      point compared to the proximal portion. This fact supports the thesis that A-wave
      is generated from the branching of immature regenerating fibers. M-wave
      conduction velocity also decreased around the reflecting point of the A-wave,
      suggesting that, in addition to moderate diabetic polyneuropathy, entrapment at
      the cubital tunnel may be involved in generating this A-wave.

PMID- 8741357
TI  - [Oligospermia improved by switching an anticonvulsant from phenytoin to
      valproate].
AB  - We report a case of 30-year-old man with generalized seizure, who had received
      phenytoin (PHT) for more than 6 years, but developed decrease in sperm count and
      motility. After PHT had been discontinued and valproate (VPA) had been
      administered for 3 months, his sperm activity became normalized. The decrease in
      sperm motility was the most important cause of his infertility. Sperm motility
      has been reported to be inversely correlated with the ratio of the concentrations
      of antiepileptic drugs in the plasma and semen. In our case, the ratio was 0.21
      for PHT and 0.08 for VPA. We wish to emphasize the importance of measuring the
      concentration of antiepileptic drugs in the semen of infertile young males if
      they are on anticonvulsants.

PMID- 8741358
TI  - [Recurring consciousness disturbance with elevation of endogenous benzodiazepine
      like activity].
AB  - A 63-year-old man had recurrent spontaneous attacks of consciousness disturbance
      without toxic, metabolic, or structural brain damage. Interictal
      electroencephalography showed 14 Hz spindle wave-like activity; ictal
      electroencephalography revealed faster basic activity. Flumazenil, a
      benzodiazepine antagonist, promptly resolved the attacks. The endogenous
      benzodiazepine-like activities in plasma and cerebrospinal fluid (measured in the
      courtesy of P. Schoch Ph. D, F. Hoffmann-La Roche Ltd, Basel, Switzerland)
      increased in the interictal period and increased more strikingly in the ictal
      period. These findings and the clinical effects of flumazenil suggest an
      involvement of an endogenous benzodiazepine-like activity in the pathogenesis of
      the attacks in this patient, as same as in a case reported by Tinuper et al
      (1992).

PMID- 8741359
TI  - [Multiple cerebral infarction after treatment with cisplatin].
AB  - A 46-year-old woman with a tumor the uterine cervix who experienced
      cerebrovascular accident as a complication of cisplatin-based chemotherapy is
      presented. Five days after the eleventh cycle of cisplatin 75 mg, intravenously,
      she had an acute onset of mild memory disturbance and right-sided weakness. On
      neurological examination, pyramidal sign was discovered on the right side. MRI of
      the brain showed multiple infarction on the left basal ganglia. There was no
      evidence of coagulopathy, vascular, or endocardial disease that may have led to a
      cerebrovascular accident. Similar characteristics in patients previously reported
      suggest that thrombosis secondary to vascular endothelial injury induced by
      cisplatin therapy may be responsible for cerebrovascular complications.

PMID- 8741360
TI  - [Abnormal head drooping in facioscapulohumeral muscular dystrophy].
AB  - Diagnosis of facioscapulohumeral muscular dystrophy (FSHD) is based on its
      characteristic pattern of muscle wasting. Initial symptom is usually shoulder
      girdle and upper arm muscle wasting resulting in difficulty in arm-lifting.
      Patients are aware of progressive change of facial appearance caused by
      characteristic facial muscle weakness. Affection of other muscles is usually
      realized much later, but, there is a considerable variation in pattern and
      severity between individuals even in the same family so that several clinical
      subtypes such as jump form or scapuloperoneal syndrome have been proposed. Here
      we described three patients with FSHD showing conspicuous head-drooping caused by
      severe wasting of posterior neck muscles. These patients realized abnormal neck
      posture much earlier than appearance of obvious gait disability, while they show
      other characteristic FSHD features. Familial occurrence is observed in two cases,
      other affected members from both families do not show abnormal head drooping.
      Therefore we regarded this sign as another example of clinical heterogeneity of
      this genetic disorder.

PMID- 8741361
TI  - [Hypertension and cardiovascular diseases in Japanese elderly].

PMID- 8741362
TI  - [Long-term prognosis of chronic heart failure in the elderly].
AB  - To elucidate the predictors of the mortality rate in the elderly with chronic
      heart failure (HF), 120 consecutive patients (mean age, 75.2 +/- 7.8 years) with
      heart failure (NYHA I-II) were analyzed prospectively for 5 years. [Methods] Left
      ventricular ejection fraction (EF), left ventricular diastolic and systolic
      dimension (LVDD and LVDS) and wall thickness (WT) were measured by
      echocardiogram. Venipuncture for measurement of ANP and norepinephrine (NE) was
      done in supine position after 30 minute rest. [Results] 1) HF was associated with
      hypertension (47.5%), ischemic heart disease (34%), valvular disease (15%) and
      atrial fibrillation (AF, 23%). 2) 15 and 11 patients died for cardiac and non
      cardiac events, respectively. 3) There was no difference in mean ages, gender,
      blood pressure, plasma-NE, EF, LVDD, LVDS, WT and AF between cardiac death and
      control groups. However, plasma ANP was higher in cardiac death group (173 pg/ml)
      than in control group (76 pg/ml) (p < 0.01). 4) Cox proportional hazard
      regression model revealed that ANP was an independent predictor for cardiac death
      (p < 0.005). We conclude that only plasma ANP level predicts long-term prognosis
      of chronic heart failure in the elderly.

PMID- 8741363
TI  - [Acute myocardial infarction and silent myocardial ischemia in the elderly-
      clinical features and effectiveness of therapy in an era of coronary
      intervention].
AB  - To elucidate the clinical features of acute myocardial infarction (AMI) and post
      MI silent myocardial ischemia (SMI) in the elderly, and efficacy of therapy in an
      era of coronary intervention, a total of 10,607 patients with AMI who were
      enrolled in a multicenter survey between 1982 and 1992 were examined. The elderly
      had a higher ratio of females, noncardiac illness, atypical symptoms at the onset
      of AMI, severe pump failure at admission, cardiac rupture and multivessel
      disease. Hospital mortality was markedly higher in patients > or = 75 years, and
      it was 4-fold compared with patients < 65 years. In the last 5 years, the rate of
      application of coronary angiography and primary PTCA significantly increased even
      in the very elderly. In contrast, use of thrombolysis highly diminished. Hospital
      mortality declined (14.6 vs 11.9%, p < 0.001) in every age group compared with
      the first 5 years, although it was higher in the elderly even in the last 5
      years. Investigation of 642 survivors after AMI admitted to one hospital showed
      that the elderly had a higher incidence of SMI and post-MI angina compared with
      the non-elderly. Clinical features of SMI were similar in both groups. However,
      medical treatment was more prevalent and recurrence of MI and cardiac death
      during follow-up (average 27 months) were more frequent in the elderly. In this
      retrospective study, characteristics of AMI and SMI, and effectiveness and
      limitation of therapy in the elderly were clearly demonstrated. It was evident
      that hospital mortality of the elderly had improved, although it was still higher
      than the non-elderly.

PMID- 8741364
TI  - [Effect of estriol and bone mineral density of lumbar vertebrae in elderly and
      postmenopausal women].
AB  - To compare the efficacy of estriol (E3) in postmenopausal and senile
      osteoporosis, we administered orally 1 g/day calcium lactate either alone
      (control groups) or with 2 mg/day estriol (estrogen groups) for 10 months to 20
      postmenopausal women aged 50-65 years and to 29 elderly women aged 70-84 years,
      and measured their bone mineral density of the lumbar vertebrae by dual energy X
      ray absorptiometry. Out of 41 subjects who completed 10 months of treatment, 8
      postmenopausal women and 12 elderly women in the estrogen groups had significant
      (p < 0.05) increases in bone mineral density (5.59 +/- 4.79% of the respective
      basal values). Ten postmenopausal women and 11 elderly women in the control
      groups had decreases bone mineral density (-4.02 +/- 7.00% and -3.26 +/- 4.60% of
      the respective basal values) at the 10th month. Genital bleeding as a side effect
      of estriol was seen in 6 out 29 elderly subjects at this dose. Moreover,
      decreases in the levels of calcium, total cholesterol, and triglycerides in
      serum, and an increase in the level of high-density lipoprotein-cholesterol were
      seen only in the elderly women receiving estriol. Although a lower dosage of
      estriol may be recommended for elderly subjects, these observations suggest that
      hormone replacement therapy with estriol is effective against degenerative
      osteoporosis, and that low-turnover bones in elderly women are also responsive to
      estriol.

PMID- 8741365
TI  - [Use of epidemiological data to predict the occurrence of arteriosclerotic
      diseases in urban residents].
AB  - From 1983 to 1986, 100,352 urban residents were screened for cardiovascular
      disease. Glucose and protein levels in urine, total cholesterol, triglycerides,
      high density lipoprotein cholesterol, blood pressure, and aortic pulse wave
      velocity were measured. Retinal examinations and electrocardiography were also
      done. A follow-up survey was conducted two years after screening. A total of
      34,895 subjects had no disease and 301 had arteriosclerotic diseases. The
      occurrence of cardio- and cerebrovascular diseases could not have been predicted
      from any one abnormal result on a screening test, but might have been predicted
      from multiple abnormal results, with each factor having its own weight and a
      unique association with other factors. The risk of disease increased
      multiplicatively higher rather than additively with the number of abnormal test
      results. We used Hayashi's quantification method III to determine which
      combination of abnormal test results was associated with a higher risk of arterio
      sclerotic diseases, and thus developed a comprehensive indicator of disease risk
      by grouping several abnormal test results that were affected by different
      factors. This evaluation system can be used to predict the onset of
      arteriosclerotic diseases to some degree and can contribute to preventive
      medicine.

PMID- 8741366
TI  - [Onset of dyspnea on exertion in elderly and young patients with congestive heart
      failure].
AB  - We previously reported that dyspnea on exertion in patients with congestive heart
      failure was not associated with pulmonary function ar rest, but was associated
      with the appearance of the anaerobic threshold and with the respiratory
      compensation point during exercise. Here we described a study of the influence of
      aging on the onset of dyspnea on exertion in elderly and in young patients with
      congestive heart failure. A total of 53 patients were studied: 35 were less than
      65-year-old (average age, 47-year-old; 19 men and 16 women) and 18 were more than
      65-year-old (average age, 70-year-old; 13 men and 5 women). All patients
      underwent maximal graded exercise testing on a bicycle ergometer. The workload
      increased according to a ramp protocol, and perceived exertion was evaluated with
      the Borg scale. The anaerobic threshold, the respiratory compensation point, and
      the peak VO2 were recorded. Values of 13 (somewhat hard) and 17 (very hard) on
      the Borg scale were considered to mark the start of dyspnea on exertion and an
      increase in dyspnea on exertion respectively. In the young patients, dyspnea on
      exertion began at about the time that the anaerobic threshold was reached, and it
      increased at about the time that the respiratory compensation point was reached.
      In contrast, elderly patients dyspnea on exertion began 70 seconds after the
      anaerobic threshold was reached, and it increased 30 seconds after the
      respiratory compensation point was reached. The VO2 at the start of dyspnea on
      exertion and the VO2 at the anaerobic threshold correlated more closely in the
      young patients than in the old patients. The same was true of the VO2 at the time
      that dyspnea on exertion increased and the VO2 at the respiratory compensation
      point. These findings suggest that elderly patients with congestive heart failure
      are less sensitive to the stimuli that cause dyspnea than are young patients.

PMID- 8741367
TI  - [University education in geriatrics. Present status and future plans of
      universities regarding the development of a program in geriatrics].
AB  - Because the number of people who reach an advanced age has been increasing at an
      unprecedented rate in Japan, geriatricians are expected to play a central role in
      health care for the elderly. However, only 16 out of 80 medical schools (20
      percent) now have departments of geriatrics for undergraduate education. To
      develop undergraduate education in the field of geriatrics, a survey was
      sponsored by the Research Projects on Aging and Health (Health Science Research
      Grant the Ministry of Health and Welfare of Japan). A questionnaire regarding the
      present status and future plans of the university about a program in geriatrics,
      was sent to deans of medical faculties or vice-presidents of medical schools. The
      questionnaire included questions about current status and future plans regarding
      undergraduate geriatric education, the presence of a department or clinic of
      geriatrics, educational requirements in the field of geriatrics, opportunities
      for practice, institutions of practice, research on geriatrics, and other
      suggestions. The response rate was 93.7 percent (74/79). Departments or clinics
      of geriatrics had been established in 15 institutions (20.3 percent) and were
      planned in 18 (24.3 percent). Undergraduate education in geriatrics was
      considered necessary in 73 schools (98.7 percent) and indispensable as an
      obligatory subject in 56 (75.7 percent). Clinical practice was considered more
      important and effective than lectures in 50 schools (63.3 percent). Coordinated
      lectures on basic biomedical gerontology (such as mechanism of aging) and
      geriatric medicine for chronic degenerative diseases such as senile dementia were
      considered essential to the curriculum. In practicing geriatrics, experience in
      providing medical care to aged patients as well as social support and a welfare
      system for the aged is emphasized. Institutions, nursing homes, and geriatric
      hospitals outside medical schools be easily accessible. It was generally agreed
      that geriatrics should be taught in advanced classes. In conclusion, medical
      schools in Japan regard undergraduate education in geriatrics as necessary and
      agree on the optimal curriculum, but it is not universally implemented.

PMID- 8741368
TI  - [University education in geriatrics. Opinions of teaching staff on undergraduate
      education in gerontology and geriatric medicine].
AB  - Undergraduate education in gerontology and geriatric medicine has become more
      important because of a progressive increase in the aged population. To assess
      curricula in geriatric medicine and to survey the opinions of teaching staffs as
      to the ideal curriculum, a questionnaire was sent to professors of gerontology
      and geriatric medicine at 14 medical schools. Responses were obtained from all 14
      professors. In all medical schools, students are given lectures in the fifth or
      sixth year, or both. The total number of hours for the lectures varied from a few
      hours to 40 hours, and contents of the lectures varied between schools. Medical
      staffs pointed out that little time is allocated to geriatric medicine. They also
      emphasized the importance of bedside teaching.

PMID- 8741369
TI  - [Correlation between periventricular lucency and extracranial arterial lesions].
AB  - This study was done to clarify relationships between the degree of
      periventricular lucency (PVL), and lesions in the carotid arteries and the legs
      as detected with B-mode ultrasonography and the ankle pressure index,
      respectively. According to the distribution of PVL on computed tomography, 45
      patients were divided into 2 groups: 22 patients with diffuse PVL (from the
      periventricular white matter to the subcortical area, DPVL group) and 23 patients
      with PVL localized in the frontal deep white matter (LPVL group). Plaque, defined
      as a thickened intima-media complex of 2.1 mm or more, was divided into two
      types; mural plaque and nodular plaque. Hypertension was more common in the DPVL
      group than in control groups, which consisted of 70 age-matched patients with
      cerebral thrombosis without PVL (CTH group) and 50 controls with neither PVL nor
      cerebrovascular lesions (NCT group). All patients in the DPVL group met the
      diagnostic criteria for Binswanger's disease proposed by Bennett DA. The
      incidence of low API indices (< 0.9) in the DPVL group (45%) was significantly
      higher than that in the NCT group, and it was slightly higher than that in the
      LPVL group. Carotid lesions, mainly nodular plaques, were seen in 82% of patients
      in the DPVL group and in 74% of those in the LPVL group; these percentages were
      significantly higher than those in the CTH (49%) and NCT (40%) groups. In
      particular, bilateral carotid lesions were more common in the DPVL group than in
      the other three groups. The degree of PVL correlated with lesions in the carotid
      arteries and the legs. These correlations suggest that the arterial lesions not
      only resulted from a risk factor (hypertension) for PVL, but also promoted PVL by
      causing extra- and intra-cranial arterial lesions. Furthermore, they imply that
      LPVL is a precusor to DPVL.

PMID- 8741370
TI  - Morphological effects of tumor necrosis factor-alpha on the blood vessels in rat
      experimental brain tumors.
AB  - The morphological changes in the vascular endothelium caused by the
      administration of tumor necrosis factor-alpha (TNF-alpha) were studied in an
      experimental model of rat brain tumors. Wistar rats bearing implanted C6 glioma
      received human natural-type TNF-alpha (1.7 x 10(5) U/m2) through the carotid
      artery and were sacrificed 3 or 24 hours later. The endothelial cells of the
      tumor blood vessels, demonstrated by the immunoreaction to factor VIII-related
      antigen, were enlarged after TNF-alpha administration. Morphometry demonstrated
      that the nuclei of these endothelial cells were also increased in size. The
      endothelial cells in the brain remote to the tumor were not affected. An in vitro
      binding study demonstrated that TNF-alpha binding sites were distributed in the
      vascular endothelial cells within the tumor but not in the brain remote to the
      tumor. The selective effect of TNF-alpha on the tumor blood vessels in
      experimental brain tumors may be related to the selective distribution of the TNF
      alpha binding site.

PMID- 8741371
TI  - Peripheral nerve regeneration in a silicone tube: effect of collagen sponge
      prosthesis, laminin, and pyrimidine compound administration.
AB  - Regeneration of transected peripheral nerve with a 10-mm gap encased in a
      silicone tube was evaluated in the presence of collagen sponge with or without
      laminin, or with systemic administration of a pyrimidine compound, MS-818. The
      sciatic nerve of 20 adult rats was transected and the proximal and distal nerve
      stumps were fixed in a silicone tube. The lumen of the silicone tube was empty,
      or filled with a collagen sponge alone or with a laminin-soaked collagen sponge.
      Also, a pyrimidine compound was injected intraperitoneally after implantation of
      the empty silicone tube. Three weeks later, the contents of the silicone tubes
      were processed for histological examination of regenerated nerve fibers. Other
      animals were observed 6, 12, and 18 months after surgery to examine the long-term
      effects of the collagen sponge on nerve regeneration. All animals had regenerated
      tissue within the tube 3 weeks after nerve transection. The diameter of the
      tissue decreased toward the distal stump in the empty tube, but was the same
      throughout the full length in the collagen sponge-containing tube.
      Immunohistochemical studies revealed that the nerve fibers extended beyond the
      midline of the regenerated tissue in animals treated with a laminin-containing
      collagen sponge or receiving a pyrimidine compound. Long-term observation showed
      the regenerated nerve was thick as the proximal stump and many neurofilament- and
      peripheral myelin-positive fibers were observed around the collagen sponge.
      Collagen sponge assists the progress of regenerated tissues in silicone tubes,
      and laminin-containing prostheses and administration of a pyrimidine compound
      enhance peripheral nerve regeneration.

PMID- 8741372
TI  - Usefulness of thallium-201 single photon emission computed tomography to quantify
      the malignancy grade of brain tumors.
AB  - Preoperative thallium-201 (201Tl) single photon emission computed tomography
      (SPECT) was used to evaluate the histological malignancy in 24 patients with
      brain tumors. A corrected L/E ratio was calculated based on the ratio of thallium
      uptake in the tumor on early images versus the tumor in the delayed images (L/E
      ratio) corrected for thallium uptake in the contralateral cerebral hemisphere.
      The corrected L/E ratio in benign brain tumors was 0.79 +/- 0.23, significantly
      different to 1.32 +/- 0.25 in high grade astrocytomas (p < 0.01) and 1.19 +/-
      0.05 in metastatic brain tumors (p < 0.01), respectively. The corrected L/E ratio
      in low grade astrocytomas was 0.64 +/- 0.32, significantly lower than that in
      high grade astrocytomas (p < 0.01) and metastatic brain tumors (p < 0.05). There
      was one false positive result among 24 patients using a threshold of 1.0 to
      separate malignant and benign tumors. 201Tl SPECT using the corrected L/E ratio
      is effective for determining the malignant viability of tumors.

PMID- 8741373
TI  - Intraoperative electrocorticography in children with medically intractable
      epilepsy.
AB  - Intraoperative electrocorticography (ECoG) was performed to localize epileptic
      foci in 20 children undergoing temporal and extratemporal surgery for intractable
      epilepsy under modified neuroleptanalgesia. Nitrous oxide gas was discontinued at
      least 15 minutes before and during preresection ECoG recording, which lasted for
      30 minutes. Seventeen patients showed epileptiform discharges on preresection
      ECoG. Hyperventilation loading, monitored by electroencephalography or ECoG in
      all patients, induced enhanced or induced epileptiform activities in 17 patients
      and provoked electroencephalographic seizures in 10 patients. All foci in non
      eloquent areas were resected. Fifteen patients have been seizure-free with
      reduced medication, and two patients have achieved worthwhile improvement.
      Habitual seizures have remained in three patients. Two of these patients had foci
      in eloquent areas which could not be resected. Intraoperative ECoG can improve
      the outcome of surgery for intractable epilepsy by localizing epileptic foci for
      resection.

PMID- 8741374
TI  - Akinetic mutism and involuntary movements following radical resection of
      hypothalamic glioma--case report.
AB  - A 3-year-old boy presented with an unusual consciousness disturbance accompanied
      by involuntary movement disorder after radical surgical removal of a huge
      hypothalamic glioma. Postoperative computed tomography and magnetic resonance
      imaging revealed a lesion in the bilateral basal ganglia. Marked neurological
      improvement was obtained by treatment with dopamine agonists, suggesting that the
      disruption of the dopaminergic pathway via the hypothalamus was the cause of
      these neurological symptoms.

PMID- 8741375
TI  - Herniation of the third ventricle into empty sella caused by surgery for
      pituitary apoplexy--case report.
AB  - A 46-year-old male presented with acute visual loss in the right eye, high fever,
      nausea, and vomiting. This was caused by herniation of the third ventricle into
      empty sella at 15 months of surgery for pituitary apoplexy. The sellar
      suprasellar tumor was totally removed via a transcranial approach. Histological
      examination showed chromophobe adenoma with necrotic tissue, indicating pituitary
      apoplexy. His visual field defect worsened 15 months after the operation, and
      magnetic resonance imaging revealed moderate hydrocephalus and protrusion of the
      dilated anterior inferior portion of the third ventricle into the sella. The
      optic nerve, optic chiasm, and pituitary gland were compressed onto the sellar
      floor. Ventriculoperitoneal shunt relieved the visual impairment. A decompressive
      procedure such as ventriculoperitoneal shunts is a reasonable treatment for such
      a marked herniation of the third ventricle.

PMID- 8741376
TI  - Acute cerebellar edema following intra-arterial tissue plasminogen activator
      thrombolysis for basilar artery occlusion--case report.
AB  - A 61-year-old male developed acute cerebellar swelling after thrombolytic therapy
      for basilar artery occlusion. He was treated with intra-arterial tissue
      plasminogen activator 12 hours following symptomatic onset, and did well in the
      immediate post-treatment period but deteriorated the next day. Computed
      tomography demonstrated acute cerebellar edema and hydrocephalus. Suboccipital
      external decompression and ventricular drainage were performed. He survived and 1
      year later he could perform daily activities at home. Computed tomography and
      angiography are essential to monitor the post-treatment course following
      thrombolysis of vertebrobasilar occlusive disease.

PMID- 8741377
TI  - Eosinophilic granuloma associated with intratumoral hemorrhage--case report.
AB  - A 2-year-old boy presented with a rapidly growing soft scalp mass in the left
      parietal region. Surgical exploration and histological examination demonstrated
      an eosinophilic granuloma associated with intratumoral hemorrhage. Eosinophilic
      granuloma should also be considered when a scalp mass lesion exhibits rapid
      growth.

PMID- 8741378
TI  - Malignant schwannoma metastasizing to the dura mater--case report.
AB  - A 58-year-old female, with a previous history of radical resection of malignant
      schwannoma arising in the maxillary sinus, presented with a metastasis to the
      dura mater following lung metastases 15 years after the initial diagnosis. A
      large mass at the left temporal region was totally removed immediately after an
      intratumoral hemorrhage. She subsequently died of massive hemoptysis. Although
      the prognosis is poor for patients with malignant schwannoma, aggressive
      treatment including radical surgery combined with radiotherapy and chemotherapy
      is recommended.

PMID- 8741379
TI  - Multiple intramedullary schwannomas--case report.
AB  - A 15-year-old boy with von Recklinghausen's disease presented with two very rare
      symptomatic cervical intramedullary schwannomas manifesting as slowly progressive
      weakness. The tumors were totally resected and he made a complete recovery.

PMID- 8741380
TI  - Uterine leiomyosarcoma metastasis to the skull--case report.
AB  - A 54-year-old female presented with a rare uterine leiomyosarcoma metastasis to
      the skull appearing as a gross mass beneath her scalp. She had no neurological or
      other physical symptoms on admission. Computed tomography and magnetic resonance
      imaging demonstrated an enhanced dumbbell-shaped mass at the mid-frontal region
      beneath the scalp. The tumor was totally removed with normal surrounding bone and
      dura. The histological diagnosis was leiomyosarcoma. Her postoperative course was
      uneventful, and she received adjuvant chemotherapy. However, multiple distant
      bone metastases developed 1 year later. Immediate and radical resection of such
      tumors is recommended.

PMID- 8741381
TI  - A preliminary study on inherited tooth morphology characters of Japanese and
      Chinese young adults--with special reference to the Carabelli tubercle.
AB  - A comparative study on inherited tooth morphology characters, in particular the
      incidence of Carabelli tubercles in the maxillary dentition, was conducted on
      standardized stone casts obtained from 240 Japanese (124 males (male) and 116
      females (females)) and 160 Chinese (74 male, 86 female) young adults. The
      following results were obtained: 1) No significant differences in the incidence
      of Carabelli tubercles according to sex or body height were found between the two
      groups. 2) However, significant differences in the incidence of Carabelli
      tubercles according to sex were found in both groups. The tubercles occurred more
      frequently in males. 3) Significant differences between the bilateral and
      unilateral occurrence of Carabelli tubercles were observed in both the Japanese
      (p < 0.05) and Chinese (p < 0.01) groups; Carabelli tubercles on upper first
      molars were always bilateral. 4) The highest incidence of Carabelli tubercles was
      found in individuals with a body height of 166 approximately 175 cm in both
      groups, and a significant difference (p < 0.05) between the 156 approximately 165
      cm and 166 approximately 175 cm groups was particularly evident in the Japanese
      adults. The authors postulate that bilateral occurrence of Carabelli tubercles
      was originally an inherited character in the molar region, but that the character
      was inhibited during the process of evolution of the masticatory system and
      regression of the molar dentition.

PMID- 8741382
TI  - Ultrastructural changes in water-clear cells of the golden hamster parathyroid
      gland after streptozotocin treatment.
AB  - The effects of streptozotocin treatment on parathyroid water-clear cells in
      golden hamsters were investigated. In the cytoplasm of the water-clear cells,
      lipid droplets were increased as compared to that of the control animals. This
      finding suggests that treatment of streptozotocin affects functional activity in
      the parathyroid water-clear cells of the golden hamsters.

PMID- 8741383
TI  - Efferents from the optic tectum to the brain stem in the Japanese quail (Coturnix
      japonica). Anterogradely biocytin method.
AB  - Efferents from the optic tectum to the brain stem in the Japanese quail (Coturnix
      japonica) were studied with the anterogradely biocytin method. After injection of
      biocytin into the ipsilateral optic tectum, labeled terminals were seen in the
      rotund nucleus (Rt), neuropil part of the ventral lateral geniculate nucleus
      (GLnv), principal part of the dorsal lateral geniculate nucleus, lateral part of
      the dorsolateral thalamic nucleus, triangular nucleus (T), superficial
      parvocellular nucleus (SPC), pretectal nucleus, pretectal area (PA), subpretectal
      nucleus, central gray matter (GC), isthimo optic nucleus (ION), magnocellular and
      parvocellular parts of the isthimo nuclei (Imc and Ipc), semilunar nucleus (SLu),
      lateral and medial pontine nuclei and reticular formation (FRM) of the medulla,
      ipsilaterally. Labeled fibers were seen in the septomesencephalic tract nucleus,
      FRM, interstitio-paraetecto-subpraetectal nucleus, and the dorsal and ventral
      tectoreticular tracts (TRd and TRv). In the contralateral brain stem, labeled
      terminals were seen in the Rt, T. FRM, PA and paramedian nucleus. The
      contralateral terminals were remarkably fewer than those of the ipsilateral side.
      The present findings of the labeled terminals of the SPC and the GC at the level
      of the mesencephalic nucleus of the trigeminal nerve (MnT), and the topographic
      projection from optic tectum to the Rt in the thalamus, were original
      observations in the avian. The labeled terminals in the GLnv, Ipc, Imc and ION
      showed topographical projections from the optic tectum. Pathways to the
      contralateral brain stem were via the commissure posterior, ventral supraoptic
      decussation, and the predorsal bundle. The present results suggest that
      tectofugal impulses in the quail relate to various functions with special
      relation to the function of the GC at the level of the MnT as well as a visual
      function.

PMID- 8741384
TI  - Prolactin in the Cestodes, Taenia solium and Taenia hydatigena: an
      immunocytochemical study.
AB  - The demonstration of prolactin in cestodes, Taenia solium and Taenia hydatigena,
      was investigated by using immunocytochemical method. PRL immunoreactivity was
      widely distributed in the CNS and PNS in the worms. In the scolex PRL-IR
      perikarya occurred in the cerebral ganglia, around the basic area of the sucker
      and the rostral border region between the rostellum and the suckers with strong
      immunoreaction, distinctly in Taenia solium. A number of PRL-IR nerve fibres were
      observed in the main nerve cords, and a few fibres in the transverse nerve
      commissure. The holdfast musculature of the scolex was innervated by the PRL-IR
      fibres. A large number of PRL positive cells with processes and nerve plexuses
      were seen in the ootype/Mehlis' gland complex, oviduct, the duct of uterum,
      seminal receptacle and its associated duct, conspicuously in Taenia hydatigena.
      PRL-IR was evident in the wall of vas efferens of tests and vas deferens. A few
      PRL positive cells occurred in the medullary parenchyma amongst testes and sent
      their varicose processes to terminate to the testes. On the wall of the main
      excretory duct a few PRL-IR cells and fibres were seen.

PMID- 8741385
TI  - The distribution and architecture of lymphatic vessels in the rat stomach as
      revealed by an enzyme-histochemical method.
AB  - Enzyme-histochemical methods of staining for 5'-nucleotidase (5'-Nase) and
      alkaline phosphatase (ALPase) were successfully applied to study the distribution
      and architecture of lymphatic vessels and their relationships to blood vessels in
      the rat stomach. Extensively lymphatic capillary networks were found in the
      gastric wall, but there were significant differences in their extent, pattern,
      distribution and structure in the four different zones: esophagus-stomach (E-S),
      forestomach-corpus (F-C), corpus-antrum (C-A) and antrum-duodenum (A-D). 5'-Nase
      ALPase double staining revealed that the 5'-Nase-positive lymphatic vessels run
      in close proximity to ALPase-positive arteries and veins. The fine blood
      capillary network was located superficially to the lymphatic network within the
      same layer in the gastric wall. The abundant lymphatic network located in the
      deep lamina propria and the lamina muscularis mucosa was always closely
      associated with the base of the lowest gastric glands, and yet no interglandular
      lymphatic capillaries were encountered in the corpus or antrum. In contrast,
      fewer lymphatic capillaries were present in the lamina propria beneath the
      squamous epithelium of the forestomach. The distribution of the well-developed
      lymphatic networks with valve-like structures in the submucosa and subserosa
      exhibited typical features, i.e., the distribution was annular in the submucosa
      and fan-shaped in the subserosa in the antrum near the duodenum. Open junctions
      of lymphatic endothelial cells were seen in the deep lamina propria and
      submucosa. Collecting lymphatics containing valves were mainly located deep in
      the submucosa and subserosa. The deep lamina propria and submucosa may play a key
      role in lymph formation and interstitial tissue fluid homeostasis as well as in
      pathological processes in certain diseases. The present findings obtained by
      interstitially injecting ultra-fine carbon particle suspensions or Evans blue
      showed that a great deal of lymph drained into the lymphatics accompanying the
      left gastric artery. The existence of a forestomach may explain the complicated
      organization and constitution of lymphatic networks in the rat stomach.

PMID- 8741386
TI  - Ramification patterns of the nerves innervating the forearm extensors in mammals
      and reptiles.
AB  - This paper discusses muscle phylogeny based on muscle innervation and defends a
      new concept of nerve-muscle specificity. Some researchers argued strongly against
      this concept in the first half of this century. However, we think their arguments
      were partially based on insufficiently examined findings of the ramification
      manner of the radial nerve. We have dissected 140 limbs of 25 species in mammals
      and reptiles to examine the manners of ramification of nerves supplying the
      forearm extensors. The pattern of the radial nerve has been revealed to consist
      of consistent and inconsistent elements. The branches to the forearm extensors
      except for the supinator follow quite consistent patterns, while the branch(es)
      to the muscle is much less consistent. Comparing the ramification patterns of the
      nerves between mammals and lizards, it can be concluded that the radial nerve in
      mammals is formed by the phylogenetic path alteration of its partial nerve fibers
      from the pathway along the flexor side in lizards to the route in the extensor
      side.

PMID- 8741387
TI  - Light and scanning electron microscopic study on the lingual papillae in the
      newborn sea otter Enhydra lutris.
AB  - The tongue of Enhydra lutris (sea otter), died from brain contusion at the first
      day of its age, was investigated by light and scanning electron microscopy in
      this study. Three types of papillae (filiform, fungiform and circumvallate
      papillae) were present on this tongue. In our evaluation, the filiform papillae
      were divided into four shapes which were conical, club-shaped, large horny and
      triangular papillae. The different types of filiform papillae were located in
      different area of this tongue. The fungiform papillae were divided into two
      shapes, which were hemispherical or club-shaped, and were distributed among the
      filiform papillae on the dorsal and the margin of the tongue. These papillae had
      many taste buds in the epithelium of the dorsal aspect of them. The circumvallate
      papillae were present in a V-shaped row at the posterior part of the lingual
      body, and many taste buds lay in the epithelium of both the lateral walls facing
      the trench and dorsal aspect of the papillary body, and then the ducts of the
      serous glands opened into the floor of the trenches. The lingual mucosa of the
      interpapillae area at the pharyngeal part of the tongue contained taste buds and
      the ducts of the mixed glands opened there. Based on our examination, the lingual
      papillae of this newborn sea otter had many features which were described to be
      peculiar to young stage of mammals.

PMID- 8741388
TI  - Chloride transport across kidney epithelia through CLC chloride channels.
AB  - This review summarizes recent progress in elucidating the chloride-transporting
      mechanisms in kidney epithelia, focusing particularly on those which act through
      the newly identified chloride channels. A family of chloride channel proteins
      (ClC chloride channels) consisting of at least 9 members (ClC-1, 2, 3, 4, 5, 6,
      7, K1 and K2) has recently been identified in mammals. Although all of these ClC
      channels, except for skeletal muscle-specific ClC-1, are expressed in the kidney,
      only ClC-K1 and K2 are kidney-specific ClC chloride channels, suggesting that
      they play an important role in the kidney. The functional properties and
      intrarenal localization of these chloride channels are summarized, and their
      involvement in certain tubular dysfunctions and physiological roles are discussed
      in this report.

PMID- 8741389
TI  - Effects of an oral adsorbent on cisplatin-induced nephropathy in rats.
AB  - A 26-week experiment was designed to determine the effect of an oral adsorbent,
      AST-120 (Kremezin), in rats with cisplatin-induced interstitial nephropathy. We
      found that creatinine clearance during the 24th week of the experiment was
      significantly higher in the AST-120-treated rats (n = 11) than in the control
      animals (n = 11) (1.09 +/- 0.14, vs. 0.63 +/- 0.12 ml/min; p < 0.05).
      Furthermore, the kidneys, which were examined morphometrically using a
      computerized image scan, revealed that the AST-120-treated rats had a
      significantly lower ratio of the tubular cross-sectional area over the cortex and
      outer medulla cross-sectional area than the control group (0.26 +/- 0.03 vs. 0.38
      +/- 0.02; p < 0.05). An additional experiment was conducted to see if the oral
      adsorbent affects absorption and excretion of intraperitoneally administered
      cisplatin. There was no difference between the control group (n = 12) and the AST
      120-treated group (n = 12) in serum concentration or urinary excretion of
      cisplatin during a 72-hour period after the injection. The results of our
      experiments suggest that the oral absorbent, AST-120, blunts progressive
      deterioration of renal function and nephron architecture in cisplatin
      nephropathy.

PMID- 8741390
TI  - Comparison of Jaffe rate assay and enzymatic method for the measurement of
      creatinine clearance.
AB  - To evaluate the relationship between Jaffe rate assay (Jaffe assay) and
      creatinine amidohydrolase enzymatic method (enzymatic method), we measured serum
      and urine creatinine concentrations in 100 serum and 100 urine samples by two
      methods in patients with renal disease. Comparison of Jaffe (X) and enzymatic (Y)
      measurements of serum and urine creatinine levels revealed a high correlation (r2
      = 0.9991 in serum, r2 = 0.9995 in urine). The creatinine concentrations in serum
      and urine determined by Jaffe assay were significantly (p < 0.01) higher than
      those assayed by the enzymatic method. The relationship between Jaffe and
      enzymatic analyses of creatinine clearance (Ccr) was obtained mathematically
      using regression lines (Y = 0.977X - 0.199 in serum, Y = 0.999X - 1.872 in
      urine). Ccr values obtained by both methods were almost the same at high serum
      creatinine levels. However, Ccr determined by Jaffe assay was much lower than
      that obtained by the enzymatic method when the serum creatinine concentration was
      under 2.0 mg/dl. We present here the equation for conversion of clearance values
      determined by both methods to obtain an accurate evaluation of renal function in
      many clinical studies.

PMID- 8741391
TI  - Elevation of plasma thrombomodulin level in primary glomerulonephritis with heavy
      proteinuria.
AB  - Thrombomodulin (TM) is a thrombin receptor found on endothelial cells. TM acts as
      a cofactor for the thrombin-catabolized activation of protein C and protects
      these cells from the formation of thrombi. We hypothesized that the soluble form
      of TM which reflects the damage of the endothelial cells and that simultaneously,
      soluble TM will be affected by renal excretion because a significant positive
      correlation has been found between soluble TM and serum creatinine (sCr) in the
      renal failure state. However, there have been no reports on the relationship
      between plasma TM and clinical parameters except for sCr in primary
      glomerulonephritis (PGN). Plasma TM (pTM) and urinary TM (uTM) were measured in
      107 patients with PGN using a one-step sandwich enzyme immunoassay. These values
      were assessed together with other laboratory and histological findings. We were
      able to divide all subjects into two groups: an sCr-dependent group whose sCr
      level was over 1.2 mg/dl and an sCr-independent group whose sCr level was under
      1.2 mg/dl. In the sCr-independent group, patients who suffered from nephrotic
      syndrome (NS) had a much higher pTM level than patients who did not suffer from
      NS. Histological findings and other parameters were not correlated with pTM or
      uTM. Therefore, the two patients who suffered from NS with very high pTM levels
      and normal sCr level at the time of admission exhibited a decrease in their pTM
      value as their condition improved. We concluded that in our patients, pTM was
      affected not only by renal excretion of TM, but also by renal damage with heavy
      proteinuria and may have been associated with an ongoing disease process in PGN.

PMID- 8741392
TI  - What is the best index of glycemic control in patients with diabetes mellitus on
      hemodialysis?
AB  - Since red blood cell survival time is shortened in patients with diabetes
      mellitus (DM) on hemodialysis (HD), it is unlikely that indices of glycemic
      control accurately reflect the glycemic state of these individuals. In this
      study, in order to determine the best index of glycemic control in diabetic
      patients on HD, we measured HbAlc, 1,5-anhydroglucitol (1,5-AG), fructosamine
      (Fr) and glycated albumin (GA) in 31 diabetic patients on HD (20 males and 11
      females, mean age: 66.9 years), and examined the correlation between each index
      and predialysis plasma glucose level. Since the mean values of predialysis plasma
      glucose during the final 2 and 4 weeks before the study were best correlated with
      HbAlc, this parameter was considered to be the most reliable index of glycemic
      control in diabetic patients on HD. GA was more closely correlated with mean
      values of predialysis plasma glucose during the final 2 and 4 weeks, than any
      other index of glycemic control, followed by HbAlc. In conclusion, HbAlc is
      considered to be the most reliable index of glycemic control in diabetic patients
      on HD.

PMID- 8741393
TI  - An epidemiologic analysis of parathyroidectomy in chronic dialysis patients. The
      Okinawa Dialysis Study Group.
AB  - Parathyroidectomy (PTX) is one of the treatments of choice for secondary
      hyperparathyroidism in chronic dialysis patients. Due to the large increase in
      long-term dialysis patients, hyperparathyroidism is becoming a common clinical
      problem. Several studies on PTX have reported various surgical procedures, but
      limited information is available on the incidence and risk factors of the
      surgery. The Okinawa Dialysis Study (OKIDS) registry is a community-based
      dialysis registry. It covers the entire area of Okinawa from when the use of
      chronic dialysis began in 1971. By the end of 1990, a total of 1,986 chronic
      dialysis patients were registered and 128 of these had undergone PTX by the end
      of 1993. The cumulative incidence of PTX was 4.3 in DM and 15.2 in non-DM per
      1,000 patient-years. About half of the PTX patients underwent the surgery within
      10 years of dialysis. By logistic analysis, the risk of PTX was seen to increase
      significantly with the duration of dialysis, P < 0.0001. Other clinical variables
      such as sex, age at the start of dialysis and the presence of diabetes mellitus
      were not significant predictors of PTX. The probability of PTX increased linearly
      with the duration of dialysis (r = 0.83, p < 0.0001). After the introduction of
      active vitamin D in 1981, the probability of PTX was significantly decreased (p <
      0.05) compared to the pre-vitamin D period ('71-'80). With prolongation of the
      duration of dialysis, the risk of PTX increased steadily and was estimated to be
      10 percent in 10 years and 20 percent in 20 years. Other uremic factors
      determining a pathological transformation of parathyroid tissue from reactive to
      autonomous growth remained to be investigated.

PMID- 8741394
TI  - [Presenilin-1 (S182) causative gene of early-onset familial Alzheimer's disease].

PMID- 8741395
TI  - [STM-2, a candidate gene for the familial Alzheimer's disease on chromosome 1].

PMID- 8741396
TI  - [APP, the causal gene for Alzheimer's disease].

PMID- 8741397
TI  - [Molecular genetics of apolipoprotein E and its receptors, implications for
      genetic risk factors of Alzheimer's disease].

PMID- 8741398
TI  - [Apolipoprotein E and its receptors in Alzheimer's disease].

PMID- 8741399
TI  - [LRP (alpha 2-macroglobulin receptor) and Alzheimer lesions].

PMID- 8741400
TI  - [Alzheimer-type dementia and related disorders: their neuropathological aspects].

PMID- 8741401
TI  - [Tertiary structure and functional sites of bombyxin, an insect insulin-like
      peptide: comparison with those of insulin].

PMID- 8741402
TI  - [Casts method for the mouse embryo vasculature].

PMID- 8741403
TI  - [Clinical application of functional mapping: the present state of the art and its
      future prospects: (series 7) magneto-encephalographic study of higher brain
      function].

PMID- 8741404
TI  - [Brain tumors and colony stimulating factors].

PMID- 8741405
TI  - [Surgical treatment for syringomyelia].

PMID- 8741406
TI  - [Usefulness of functional image of dynamic computed tomography (FID-CT) on acute
      cerebral ischemic disease: correlation between parameters of dynamic CT and
      angiographical findings].
AB  - We reported the correlation between the angiographical findings and parameters of
      the functional images of dynamic CT (FID-CT) in ten patients with cerebral
      ischemic disease. Six of these ten patients with an abnormal area on corrected
      mean transit time (CM) and time to peak (TP) had complete occlusion of
      intracerebral main arteries with poor collateral cerebral blood flow or no
      collateral flow on the angiography. Four patients with prolonged time only in the
      TP area, but not in the CM area, had stenosis or occlusion of the main trunk with
      satisfactory anterograde cerebral blood flow on the angiography. FID-CT is easy
      to apply for clinical use and said to be useful to predict arterial trunk
      occlusion or infarction volume. It might also be helpful to get further
      information about the intracerebral circulation disorders in the acute stage of
      cerebral ischemic disease.

PMID- 8741407
TI  - [Effects of traumatic subarachnoid hemorrhage on pathological properties in
      diffuse brain injury: a comparison with aneurysmal subarachnoid hemorrhage].
AB  - As a result of recent advances in continuous monitoring equipment, it has been
      reported that vasospasm (VS) and delayed ischemic neurological deficit (DIND)
      occur as frequently in traumatic subarachnoid hemorrhage (TSAH) as in
      subarachnoid hemorrhage due to ruptured intracranial aneurysm (ASAH), and these
      VS and DIND have been reported to affect the outcome of TSAH adversely in many
      cases. When we compared TSAH secondary to diffuse brain injury (DBI) with ASAH,
      however, these two conditions were evidently different from each other in nature.
      Then we compared laboratory data, clinical course, and outcomes of TSAH
      associated with DBI with those of ASAH, to determine whether TSAH results in poor
      outcomes of DBI. On CT scans, patterns of SAH distribution were different from
      each other, and SAH was detected in 76% of the patients with ASAH on day 4,
      whereas only 2.0% of the patients with TSAH had detectable SAH on day 3. The
      incidence rates of detectable SAH in both groups remained significantly different
      from each other after day 2. The cerebral blood flow (CBF) decreased to around
      75% of the normal flow in the acute stage of ASAH, and it decreased further to
      around 65% in the subacute stage. In TSAH, in contrast, CBF varied widely among
      the patients. The average CBF decreased to about 70% in the acute stage, and then
      it increased to around the lower limit of the normal range in the subacute stage.
      The urinary output and serum concentration of low molecular protein compositions
      in TSAH were markedly different from those in ASAH. In addition, the contour of a
      low density area (LDA) in CT scans in the subacute-chronic stage was the same as
      that of the area supplied by the artery being constricted due to cerebro-vascular
      spasm in ASAH. In TSAH, in contrast, hardly any LDA had a form that was
      suggestive of this conjuction, with cerebro-vascular spasm and the incidence rate
      of LDAs was significantly different from that for ASAH. About 30% of the patients
      with ASAH had ventricular enlargement, which was diagnosed as normal pressure
      hydrocephalus by cisternography, in the chronic stage. Surgical shunting was
      effective for these patients. In TSAH, ventricular enlargement was observed in
      more than 50% of the patients, but almost none of these patients underwent
      surgical shunting, because it resulted from cerebral atrophy. Regardless of
      causes of SAH, the severer SAH was, the more often patients had a poor outcome.
      The outcome of TSAH was, however, significantly poorer than that of ASAH. When
      SAH was traumatic, it disappeared by the time VS developed and, in addition,
      changes in CBF and the form and incidence rate of LDAs were different from those
      in ASAH. We concluded that, although TSAH is an adverse prognostic factor for
      DBI, it does not contribute to poor outcomes of DBI by giving rise to DIND caused
      by VS.

PMID- 8741408
TI  - [A retrospective analysis of the outcomes of patients with aneurysmal
      subarachnoid hemorrhages: a focus on the prognostic factors].
AB  - The authors report a clinical analysis of the outcomes of aneurysmal subarachnoid
      hemorrhages in 112 patients. Cerebral angiography was conducted on 85 patients.
      Clipping or wrapping of the aneurysm was performed on 81 patients. The overall
      good outcome (GR and MD in the Glasgow Outcome Scale) ratio and mortality rate
      were 43% and 34%, respectively. The good outcome ratio and mortality rate in
      operative cases were 59% and 12%, respectively. With regard to the timing of the
      operation, 77 cases (95%) underwent early operation and 4 cases (5%) underwent
      delayed operation. The good outcome ratio of patients with grade I to III at
      surgery using the Hunt and Kosnik grading system was 74%. There was no difference
      in outcome between the patients with a ruptured aneurysm in the anterior
      circulation and those with one in the posterior circulation. The retrospective
      analysis of the overall outcomes showed the risk factors as being: age over 70
      years, cerebral atherosclerosis, poor grade on Hunt and Kosnik grading system and
      symptomatic vasospasm. Preoperative bleeding of the aneurysm, severe brain
      swelling at surgery, and postoperative symptomatic vasospasm were factors which
      worsen the outcome of surgically treated patients. Patients with more than 2
      factors showed worse outcomes than those with only one factor. The utilization of
      these prognostic factors should be important to improve the outcome of patients
      with aneurysmal subarachnoid hemorrhage.

PMID- 8741409
TI  - [Morphological and clinical study of acoustic tumor with respect to enlargement
      of internal auditory canal: mechanism of bone destruction].
AB  - The mechanism of widening of the internal auditory canal (IAC) by an acoustic
      tumor is still unknown. Degree of IAC enlargement was expressed as "IAC ratio'
      calculated from the measurement of bilateral horizontal diameters from bone
      imaging CT. Comparing IAC ratio to radiological findings of tumors, such as size,
      solidity, mode of attachment to pyramidal bone and the presence of ventricular
      dilatation, we found a positive correlation between the ratio and the volume of
      solid tumors (especially of smaller ones) and more marked destruction of IAC in
      association with ventricular dilatation. Preoperative degrees of hearing ability
      or facial nerve function didn't correlate with that of IAC enlargement. It is our
      hypothesis that the mechanism involved in the destruction of IAC is as follows:
      (1) The repeated strokes of the tumor caused by brain pulsation gradually erode
      the bony wall of IAC (especially, that of the posterior wall). The apparently
      less destruction of IAC in cases with mostly cystic large tumors might be due to
      the restriction of this pulsatile movement. (2) Increased CSF pressure on the
      site has some influence on the mechanism of bone erosion as also does solidity of
      the tumor.

PMID- 8741410
TI  - [Adult-onset aqueductal stenosis caused by membranous occlusion in the aqueduct:
      a case report].
AB  - The authors report a case of adult-onset aqueductal stenosis caused by membranous
      occlusion of the aqueduct. The patient was a 35-year-old man, who suffered from
      progressive headache. On admission, computed tomography (CT) scan showed marked
      dilatations of the lateral and third ventricles. Midsagittal T1-weighted magnetic
      resonance imaging (MRI) scan showed a membranous occlusion at the lower end of
      the aqueduct, with dilatation of the proximal aqueduct and elevation of the
      tectum. Midsagittal cine-MRI demonstrated the cerebrospinal fluid flow in the
      aqueduct. The patient was diagnosed as having hydrocephalus resulting from
      membranous stenosis of the aqueduct by MRI. A ventriculo-peritoneal shunt
      operation was performed and his symptoms improved markedly. The membranous
      occlusion of the aqueduct is a rare cause of hydrocephalus. The etiology and
      therapy of aqueductal stenosis are discussed.

PMID- 8741411
TI  - [Central retinal vein occlusion after embolization for spontaneous carotid
      cavernous sinus fistula].
AB  - A patient with spontaneous carotid-cavernous sinus fistula, who developed central
      retinal vein occlusion (CRVO) after interventional surgery, was reported. A 78
      year-old woman was admitted with symptoms of right abducens palsy and
      conjunctival injection. Digital subtraction angiography (DSA) revealed bilateral
      carotid cavernous sinus fistulas supplied by dural branches of the carotid
      arteries. After embolization of the feeding arteries and the right cavernous
      sinus using PVA and platinum coils respectively, her symptom improved gradually.
      Six months after the embolization, she was readmitted because of blurred vision
      and abducens palsy on the left side. Engorgements of the cavernous sinuses and
      draining veins, and the shunt flow of the fistula were much less on DSA than
      those seen previously, but ophthalmologic studies showed an impending central
      retinal vein occlusion (CRVO) in her left eye. Prognosis of CRVO is generally
      poor. We discussed the mechanism of CRVO occurring after interventional surgery
      for CCF and the tactics for preventing it, and early detection of its
      development.

PMID- 8741412
TI  - ["High jugular bulb": clinical feature, radiographical findings and differential
      diagnosis, a case report].
AB  - Anatomically, the top portion of the jugular bulb lies just below the floor of
      the hypotympanum. In rare instances, it can protrude upward and elevate the floor
      of the hypotympanum thus placing it in the middle ear. Such a case is called high
      jugular bulb. This anatomical variation has been found in 3.5% to 6% of the
      temporal bones studied in several reports. But, clinically, only 43 cases have
      been reported, because in most cases they are asymptomatic. A 17-year-old female
      was hospitalized with right hearing disturbance and dizziness. Neurootological
      examination revealed sensory neuronal hearing disturbance. A caloric test was
      scaled out. Axial bone window CT scan demonstrated an enlarged jugular bulb and
      an extended upward projecting hypotympanum. MRI indicated flow void in the same
      region. Retrograde jugulography has been the most useful method for diagnosis but
      we were able to diagnose it by noninvasive MR angiography. High jugular bulb is
      an unfamiliar disease entity for neurosurgeons, but we should remember that it is
      one of the differential diagnosis for c-p angle regions or jugular foramen
      regions.

PMID- 8741413
TI  - [A case of effective decompression at the first segment of the vertebral artery
      for intractable vertigo].
AB  - Atherosclerotic change is the main reason for vertebrobasilar insufficiency.
      However, if clinical symptoms such as vertigo happen transiently and repeatedly
      with head movement, vascular insufficiency due to mechanical compression of the
      vertebral artery must be kept in mind as its cause. The patient was a 54-year-old
      male complaining of recurrent vertigo which occurred during head rotation. He had
      been treated medically before he came to our hospital. Right compressed vertebral
      angiogram with head turned to the right and left compressed vertebral angiogram
      with head turned to the left were obtained at the first segment. Unilateral
      decompression of the vertebral artery was performed. At surgery it was found that
      the right vertebral artery was compressed by a stellate ganglion. After cutting
      of the sympathetic chains, the stellate ganglion was detached from the vertebral
      artery. The patient's intractable vertigo immediately disappeared after this
      procedure. It is concluded that if severe vertigo or dizziness is repeated under
      certain conditions, we must perform a bilateral vertebral angiogram and
      differentiate whether it is a case of decompression or not and then take measures
      to bring about decompression effectively.

PMID- 8741414
TI  - [A case of spontaneous rhinorrhea detected by SPAMM-tagging method].
AB  - This is the first report of rhinorrhea detected by special modulation of the
      magnetization (SPAMM)-tagging method. A 54-year-old male was admitted to our
      hospital for treatment of right rhinorrhea which had continued for 2 months and a
      half. The CSF leakage was induced by specific head position and the volume was
      more than 50 ml a day. Metrizamide CT cisternography revealed the contrast medium
      in the lateral extension of the right sphenoid sinus. MRI demonstrated liquorrhea
      with abnormal intensity of the sinus. 3D-CT revealed bony defects at the temporal
      base. Operation revealed herniated brain through the same bony defect of the
      temporal base into the extended sphenoid sinus. Post-operative diagnosis was
      Morley's rhinorrhea. The leakage point was closed and patched with the femoral
      fascia. Preoperative SPAMM-tagging image with cine MRI was useful to identify the
      responsible leakage point as a disorder of lattice tags. This method is a kind of
      flowmetry with MRI and is very effective because it can detect non-invasively
      slight CSF motion into the sinuses. It can also detect the direction and rough
      flow volume of rhinorrhea, so may also predict the risk of meningitis. The
      disadvantages were also discussed.

PMID- 8741415
TI  - [Single dose toxicity studies of calcipotriol (MC903) in rats and dogs].
AB  - A single dose toxicity of calcipotriol (MC903), an anti-psoriasic agent,
      administered subcutaneously (s.c.) and percutaneously (p.c.) was studied in
      Slc:SD rats (s.c. and p.c.) and beagle dogs (s.c.). The LD50 values of MC903 were
      as follows: rats, 2.19 mg/kg in males and 2.51 mg/kg in females by s.c., and more
      than 15 mg/kg in both sexes by p.c.; dogs, more than 1.5 mg/kg in males by p.c.
      No sexual difference was noted in LD50 values of rats. Death of rats was observed
      from 1 to 3 days after administration by both routes. Dead animals showed
      decreases in body weight and locomotor activity, reddish tear, abnormal gait and
      dirty hair by both routes. Furthermore, dead animals administered by s.c. showed
      salivation, nasal discharge, piloerection, ptosis, diarrhea, urorrhea, nasal and
      vaginal bleeding, subnormal temperature, loose stool, cyanosis, irregular and
      deep respirations, clonic and tonic convulsions. Survival of rats showed similar
      signs to those of dead animals except for nasal discharge, nasal and vaginal
      bleeding, cyanosis, agonal respiration and convulsion. Discoloration of the
      kidney, white patch of the heart and a dilatation of the stomach wall were
      observed on macroscopic examinations. No mortalities were observed in dogs which
      showed vomiting, conjunctival congestion, circumoral and auricular reddenings,
      periblepharal purplish reddening, decreases in locomotor activity and defecation,
      emaciation, eye discharge, skin desquamation of treated area and an increase in
      respiration. On macroscopic examination, desquamation of the skin, reddening of
      the circumoral mucosa, pale gray yellow striations in renal tubules of the cortex
      and discoloration of the thyroid were observed. Histopathological findings
      revealed epidermal thickening with parakeratosis, fibrocytes, hypertrophy and
      hypersecretion of the sebaceous and sweat glands, formation of epitheloid
      glanulomas and infiltration of neutrophils in the subcutaneous tissues.
      Furthermore, moderate calcium deposits in the renal tubules, fatty cells and
      slight calcium deposits in interstitial tissues of the thyroid, and a cystic nest
      of an ectopic intestinal epithelium between muscle layers of the duodenum were
      observed at the highest dose. On the basis of results obtained in the present
      study, rats administered MC903 by s.c. or p.c. died probably due to the
      circulatory and renal disturbance resulted from effects of this drug on the heart
      and kidney.

PMID- 8741416
TI  - [A 4-week repeated percutaneous dose toxicity study of calcipotriol (MC903)
      followed by a 4-week recovery test in rats].
AB  - A 4-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti
      psoriasic agent, followed by a recovery for 4 weeks was studied in Slc:SD rats at
      doses of 4, 20 and 100 micrograms/kg/day as low, mid and high dose levels. 1. One
      male and female at high dose died probably due to stress and circulatory failure.
      One female at mid dose died with clonic convulsion considered to be results in
      attached error of a neck collar. Survival of rats showed reddish tear, reddening
      and desquamation of the skin at application site, and vocalization at all groups
      including control. Furthermore, abnormal gait, dirty hair, emaciation and opacity
      of the eyeball surface in both sexes were observed at high dose. 2. A decreased
      body weight and a slight increased water consumption in both sexes, and a
      decreased food consumption in males were observed at high dose. 3. An increased
      incidence of corneal opacity was noted significantly in both sexes as compared
      with control at high dose. Urinalysis revealed an increased Ca excretion in both
      sexes at more than mid dose, and lower pH in females at mid dose and in both
      sexes at high dose, and a decreased urinary volume in males at high dose. The
      increases of neutrophil and serum beta-globulin ratios in females, and serum Ca
      level in both sexes were observed at high dose. The increased mineralization of
      the cornea in males at mid dose and in both sexes at high dose, and of the Kidney
      in males at high dose were observed. At the skin of application site, cellular
      infiltration in the epidermis and dermis in both sexes at more than mid dose was
      observed. Furthermore, hyperplasia of the squamous cell in females, and
      hyperkeratosis in the epidermis and hypertrophy of the sebaceous gland in both
      sexes were observed at high dose. 4. After a 4-week recovery period, the changes
      related with application disappeared except for opacity of the eyeball surface
      and cornea, and mineralization of organs. 5. On the basis of results obtained in
      the present study, it is considered that 4 micrograms/kg/day is the no-toxic dose
      of MC903 applied percutaneously in both sexes of rats.

PMID- 8741417
TI  - A 4-week repeated percutaneous dose toxicity study of calcipotriol (MC903)
      followed by a 4-week recovery test in dogs.
AB  - A 4-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti
      psoriasic agent, followed by a 4-week recovery was studied in beagle dogs at
      doses of 0.04, 0.4 and 4 micrograms/kg/day. 1. In general conditions, reddening,
      desquamation, rash, and wet and hot skin were observed at the skin of application
      site at 4 micrograms/kg/day. 2. In urinalysis, a tendency to an increase in Ca
      level, was observed at 4 micrograms/kg/ day. In hematology, an increase in the
      segmented neutrophils and tendency to a decrease in the lymphocyte counts were
      observed at 4 micrograms/kg/day. In biochemistry of serum, an increase in gamma
      globulin ratio, and decreases in A/G and albumin ratios were observed at 4
      micrograms/kg/day. 3. In organ weights, tendency to decreases of the absolute and
      relative weights in the thymus was observed at 4 micrograms/kg/day. 4.
      Histopathological examination revealed squamous cell hyperplasia and
      hyperkeratosis at the skin of application site at 4 micrograms/kg/day. 5. The
      above changes disappeared after the 4-week recovery period and suggested that
      they were reversible. 6. On the basis of results obtained in the present study,
      it is considered that 0.4 microgram/kg/day is the no-toxic dose of MC903 applied
      percutaneously in both sexes of beagle dogs.

PMID- 8741418
TI  - [A 26-week repeated subcutaneous dose toxicity study of calcipotriol (MC903)
      followed by a 5-week recovery test in rats].
AB  - A 26-week repeated subcutaneous dose toxicity of calcipotriol (MC903), an anti
      psoriasic agent, followed by a recovery for 5 weeks was studied in Slc:SD rats at
      doses of 0.4, 2 and 10 micrograms/kg/day as low, mid and high dose levels. 1. No
      mortality during the experimental period was observed in both sexes of all groups
      including control. An increased incidence of opacity of the eyeball surface in
      males was noted at high dose. There were no difference in body weight and food
      consumption between control. An increased water consumption in both sexes was
      observed at high dose. 2. An increased incidence of the corneal opacity was noted
      significantly at high dose in both sexes compared with that observed in control.
      Urinalysis revealed the increased excretions of Ca at more than mid dose, and Na,
      Cl and IP in males at high dose, and an decreased urinary volume in females and
      lower pH in both sexes at high dose. An increased serum Ca level in males at mid
      dose and in both sexes at high dose, and an elevated ALP activity in males at
      high dose were observed. The increased weights of the kidney in males at more
      than mid dose and adrenal gland in both sexes at high dose were observed. The
      increased incidence of mineralization of the cornea and kidney was noted
      significantly in males at more than mid dose as compared with control. Dilatation
      of endoplasmic reticulum of distal tubular cells of the kidney in both sexes was
      observed at high dose on electron microscopic examination. 3. After a 5-week
      recovery period, the changes related with the treatment of MC903 almost
      disappeared except for mineralizations of the cornea and kidney. 4. On the basis
      of results obtained in the present study, it is considered that 0.4
      microgram/kg/day is the no-toxic dose of MC903 administered subcutaneously in
      both sexes of rats.

PMID- 8741419
TI  - [A 26-week repeated percutaneous dose toxicity study of calcipotriol (MC903) in
      rats].
AB  - A 26-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti
      psoriasic agent, was studied in Slc:SD rats at doses of 0.8, 4 and 20
      micrograms/kg/day as low, mid and high dose levels. 1. No mortality were observed
      in both sexes of all groups including control. An increased water consumption was
      observed in females at mid dose and in both sexes at high dose. 2. An increased
      incidence of the corneal opacity in males at mid dose and in both sexes at high
      dose was noted significantly as compared with that observed in control.
      Urinalysis revealed a slight increased urinary volume, increased excretions of Ca
      and IP, and lower pH in both sexes at more than mid dose. Levels of the serum IP
      in females and Ca in both sexes were elevated at high dose. 3. The increased
      weights of the kidney in males and adrenal gland in females were observed at high
      dose. The kidney in females at mid dose and in both sexes at high dose showed a
      higher incidence of mineralization than in control. Furthermore, osteosclerosis
      of the sternum and femur in both sexes, and hyperkeratosis of the skin at
      application site in females at high dose were observed. Electron microscopic
      examination revealed no abnormality in the liver and kidney. 4. On the basis of
      results obtained in the present study, it is considered that 0.8 microgram/kg/day
      is the no-toxic dose of MC903 applied percutaneously in both sexes of rats.

PMID- 8741420
TI  - [A 26-week repeated percutaneous dose toxicity study of calcipotriol (MC903) in
      dogs].
AB  - A 26-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti
      psoriasic agent, was studied in beagle dogs at doses of 0.04, 0.4 and 4
      micrograms/kg/day. 1. In general conditions, reddening, rash, desquamation,
      pruritus, wet and hot skin at 4 micrograms/kg/day, reddening, rash and
      desquamation at 0.4 microgram/kg/day, pruritus and desquamation at 0.04
      microgram/kg/day, were observed at the skin of application site. 2. In
      urinalysis, an increase or a tendency to an increase in Ca level, were observed
      at 4 micrograms/kg/day. 3. Histopathological examinations revealed squamous cell
      hyperplasia and parakeratosis at the skin of application site in both sexes at 4
      micrograms/kg/day. However, these findings were not shown at the skin of
      application site at 0.4 and 0.04 microgram/kg/day. 4. On the basis of results
      obtained in the present study, it is considered that 0.4 microgram/kg/day is the
      no-toxic dose of MC903 applied percutaneously in both sexes of beagle dogs.

PMID- 8741421
TI  - [Reproductive and developmental toxicity studies of calcipotriol (MC903): (1)--A
      fertility study in rats by subcutaneous administration].
AB  - Calcipotriol (MC903), an anti-psoriasic agent, was given subcutaneously at dose
      levels of 1, 5 and 25 micrograms/kg/day during the pre-pairing period (9 weeks
      prior to pairing in males and 2 weeks prior to pairing in females) and the
      pairing period to male and female rats and in the early stage of pregnancy (day 0
      through 7 of gestation) to female rats, and the effects of the test compound on
      male and female reproductive performance and fetal development were evaluated. 1.
      In the male 25 micrograms/kg group, opacity of the eyeball surface was observed,
      and depression of body weight gain, and decreases of body weight and food
      consumption, and increases in the weight of the kidney were statistically
      significant in comparison with vehicle controls. 2. In the female 25
      micrograms/kg group, depression of body weight gain and food consumption were
      statistically significant in comparison with vehicle controls. 3. No changes in
      parameters of reproductive performance were seen in any dosed groups. 4. No
      changes in parameters of implantation performance were seen. There were no
      treated-related abnormalities in fetal mortality, weights of fetuses, and
      external, visceral and skeletal examinations. Based on there results, it is
      considered that in the present study the no-toxic dose levels of MC903 were 5
      micrograms/kg/day for parents, 25 micrograms/kg/day for reproductive performance
      and fetal development.

PMID- 8741422
TI  - [Reproductive and developmental toxicity studies of calcipotriol (MC903): (2)--A
      teratogenicity study in rats by subcutaneous administration].
AB  - Teratogenicity of calcipotriol (MC903), an anti-psoriasic agent, was studied.
      MC903 at doses of 6.25, 12.5 and 25 micrograms/kg/day were subcutaneously
      administered to pregnant Slc:SD rats from day 7 to 17 of gestation. 1. In animals
      administered 25 micrograms/kg/day MC903, food consumption decreased significantly
      and body weight gains lowered marginally. MC903 administered at any doses did not
      adversely affect female animals in regard to pregnancy, delivery and maternal
      behavior. 2. In fetuses, suppression of growth were noted at 25 micrograms/kg
      group. However, fetotoxicity and teratogenicity were not noted at all groups
      administered MC903. 3. In F1 pups, the postnatal growth, development, responses,
      behaviors, learning ability and reproductive ability were not influenced.
      Additionally, no embryonic or fetal abnormalities of their fetuses (F2) were
      detected. 4. On the basis of results obtained in the present study, it is
      considered that the no-toxic doses level of MC903 are 12.5 micrograms/kg/day for
      pregnant animals and fetuses, 25 micrograms/kg/day for pups.

PMID- 8741423
TI  - [Reproductive and developmental toxicity studies of calcipotriol (MC903): (3)--A
      teratogenicity study in rabbits by subcutaneous administration].
AB  - Teratogenicity of calcipotriol (MC903), an anti-psoriasic agent, was studied.
      MC903 at doses of 0.1, 0.5, 1, 2.5 and 5 micrograms/kg/day was subcutaneously
      administered to pregnant Std:NZW rabbits from day 6 to 18 of gestation. 1. A
      decrease in locomotor activity was observed in the group administered MC903 5
      micrograms/kg/day. Food consumption and body weight gain decreased dose
      dependently in groups administered MC903 1 microgram/kg/day or more. Granular
      whitish kidneys were observed in groups administered MC903 2.5 and 5
      micrograms/kg/day. Rough and whitish aorta were noted in groups administered
      MC903 1 microgram/kg/day or more. 2. Significant fetotoxicity was not induced by
      administration of MC903 up to 0.5 microgram/kg/day. 3. On the basis of results
      obtained in the present study, it is considered that no-toxic dose level of MC903
      is 0.5 microgram/kg/day for pregnant animals and fetuses.

PMID- 8741424
TI  - [Reproductive and developmental toxicity studies of calcipotriol (MC903): (4)--A
      perinatal and postnatal study in rats by subcutaneous administration].
AB  - Perinatal and postnatal toxicity of calcipotriol (MC903), an antipsoriasic agent,
      was studied. MC903 at doses of 6.25, 12.5 and 25 micrograms/kg/day were
      subcutaneously administered to pregnant Slc:SD rats from day 17 of gestation to
      day 21 after delivery. 1. Administration of MC903 at any doses did not adversely
      affect pregnant animals in regard to gestation, delivery and maternal behavior.
      In dams administered MC903 25 micrograms/kg/day, food consumption and body weight
      gain were marginally lower than those of control animals during lactation period.
      2. In group administered MC903 25 micrograms/kg/day, body weight gain in F1
      offsprings was significantly lower as compared with those of control group. The
      drug did not have any adverse effects on the postnatal development of the
      offspring such as differentiation, functional development, emotionality, motor
      ability, learning ability or reproductive performance. 3. On the basis of results
      obtained in the present study, it is considered that the no-toxic dose level for
      general toxicity and reproduction in the dams was estimated to be 12.5 and 25
      micrograms/kg/day, respectively, the no-toxic dose levels in the offspring was
      also estimated to be 12.5 micrograms/kg/day.

PMID- 8741425
TI  - [An antigenicity study of calcipotriol (MC903)].
AB  - Antigenicity of calcipotriol (MC903), an anti-psoriasic agent, was investigated
      in mice and guinea-pigs. 1. In mice, MC903 administered alone or with an adjuvant
      (Alum) did not result in the production of MC903-specific IgE antibody. 2. In
      guinea-pigs sensitized with MC903 alone or plus an adjuvant (FCA), systemic
      anaphylaxis was not induced by challenging with MC903. IgG1 antibody in MC903
      sensitized guinea-pigs was not detected by the 4-hr PCA test. 3. Ovalbumin
      induced the production of ovalbumin-specific IgE antibody in mice, and ovalbumin
      specific IgG1 antibody in guinea-pigs. Intense systemic anaphylaxis in the
      ovalbumin-sensitized guinea-pigs was induced by challenging with ovalbumin. 4.
      Results obtained in the present study suggest that MC903 does not induce the
      production of IgE antibody in mouse, and IgG1 antibody in guinea-pig, and in
      MC903-sensitized guinea-pig systemic anaphylaxis is not induced by challenging
      with MC903.

PMID- 8741426
TI  - [A mutagenicity study of calcipotriol (MC903)].
AB  - Calcipotriol (MC903), an anti-psoriasic agent, was examined for mutagenicity in
      the reverse mutation test and the chromosomal aberration test in vitro, and the
      micronucleus test in Slc:ddY mice. 1. In the reverse mutation test using
      Salmonella typhimurium (TA100, TA1535, TA98, TA1537) and Escherichia coli
      (WP2uvrA), MC903 did not significantly increase revertant colonies in any of the
      test strains with or without metabolic system. 2. In the chromosomal aberration
      test with a Chinese hamster fibroblast cell line (CHL), MC903 did not
      significantly increase aberrant cells in the direct method or in the activation
      method. 3. In the micronucleus test with male mice, MC903 did not significantly
      increase in the number of polychromatic erythrocytes with micronuclei in the bone
      marrow. These results suggest that MC903 has no mutagenic as well as clastogenic
      effects under the present experimental condition.

PMID- 8741427
TI  - [Dermatotoxicity studies of calcipotriol (MC903) ointment--primary skin
      irritation, skin sensitization, phototoxicity and skin photosensitization].
AB  - MC903 ointment was studied on primary skin irritation in rabbits and skin
      sensitization, skin photosensitization and phototoxicity in guinea-pigs. 1. MC903
      ointment, ointment base and deteriorated MC903 ointment induced erythematous
      changes in rabbit skin. These erythematous changes were not so serious, and they
      were classified as a mild irritant. 2. MC903 ointment was almost negative in skin
      sensitization study. 3. MC903 ointment has no skin phototoxicity in guinea-pigs.
      4. MC903 ointment has no skin photosensitizing activity in guinea-pigs.

PMID- 8741428
TI  - [Pathology of infective endocarditis].
AB  - Clinico-pathological studies were made of 40 patients with infective endocarditis
      : 34 (22 men, 12 women ; ages, 5-71 years, mean, 40.4 years) had native valve
      endocarditis (NVE) and 6 (3 men, 3 women ; ages, 26-48 years, mean, 38.3 years)
      had prosthetic valve endocarditis (PVE). The aortic valve was involved most
      frequently (AV : 16, MV : 6, AV+MV : 8, TV : 3, MV+TV : 1). Thirteen patients had
      preexsisting heart disease (rheumatic in 4, floppy in 6, other in 3). Six of 21
      "normal" valves showed myxomatous changes with connective tissue degradation,
      findings compatible with the histological diagnosis of floppy valve. The
      infecting organisms were identified by blood cultures in 26 patients. Bacteria
      and/or fungi were found histologically in 23 valves, even in those in which
      cultures of excised tissues were negative. In 2 cases, fungi were identified in
      the sewing ring of the prosthetic valves. This study demonstrates that : 1)
      floppy valve is a most important underlying heart disease in NVE ; 2) the
      infecting organisms are frequently identified histologically, even when cultures
      of excised tissues are negative ; and 3) fungi are important causes of both NVE
      and PVE, especially in patients given intensive antibiotic therapy.

PMID- 8741429
TI  - [Surgical treatment of aortic valve endocarditis associated with aortic root
      aneurysm and abscess].
AB  - Between Jan. 1979 and Mar. 1996, aortic root abscess and aneurysm were
      encountered in 10 (34.5%) of the 29 patients who underwent surgical treatment for
      the aortic valve endocarditis ; native valve endocarditis (NVE) in 8 and
      prosthetic valve endocarditis (PVE) in 2. Noncoronary sinus was involved in 8
      (80%) of 10 patients, left coronary sinus destructed in one, and more than one
      sinus were involved in one. All patients underwent aortic valve replacement after
      repair of abscess or aneurysm with suture closure in 5, and patch closure in 3,
      and its resection in one. Aortic root reconstruction using a valved conduit was
      required for the repair of aortico-ventricular discontinuity followed debridement
      of the abscess cavity of almost entire annulus in one PVE patient who
      consequentry died of LOS and sepsis. There was no operative or postoperative
      death in the other patients, however, one female patient suddenly died 24 months
      after surgery. She underwent direct suture closure of left coronary sinus
      aneurysm and aortic valve replacement with a small-sized prosthetic valve. Suture
      dehiscence of the orifice of the aneurysm developed immediately after surgery. It
      is concluded that patch closure of aortic root aneurysm or abscess is recommended
      so as to avoid narrowing of left ventricular outflow tract and recurrence of
      aneurysm formation even if its orifice proved to be small.

PMID- 8741430
TI  - [Valve replacement concomitant with anulus reconstruction].
AB  - It is important that surgical treatment of infective endocarditis involves
      complete debridement of the affected tissue. In case of abscess formation in the
      mitral anulus and/or aortic root, disruption of the anulus occurs because of
      radical resection of the abscess. David et al. reported a new technique for
      mitral and aortic anulus reconstruction. The novel part of the technique was the
      endocardial repair, i.e., suturing of a pericardial patch to the endocardium of
      the left ventricle. We were surprised to learn that the left ventricular
      endocardium and muscle are capable of tolerating the stress induced by the
      prosthetic ring, especially in the mitral position. Since 1992, we treated eight
      cases of anulus disruption using this technique ; 5 cases involved the mitral
      anulus, 1 involved the aortic, and 2 involved both. We used a slightly different
      technique involving suturing of a patch not only to the left ventricular
      endocardium but also to left atrial wall for reinforcement. Two patients died in
      the perioperative period. One had a brain abscess ; the other had methicillin
      resistant Staphylococcus aureus sepsis and mediastinitis. There was 1 late
      (sudden, unknown) death 3 years after the operation. No perivalvular leakage,
      dehiscence of the patch, hemolysis, prosthetic valve endocarditis, or
      thromboembolism have been observed in the other 5 patients.

PMID- 8741431
TI  - [Underlying cardiac disease in infective endocarditis].
AB  - Underlying cardiac lesions in 39 adult cases with infective endocarditis were
      studied. 18 cases (46%) of the patients had no evidence of preexisting cardiac
      disease and infection frequently involved aortic valve. The patients without
      preexisting cardiac disease and 4 patients with an intracardiac substitute
      including pacemaker lead and aortic valve prosthesis required a surgery during an
      active infective endocarditis. All cases of active infective endocarditis
      accompanied with rheumatic valvular disease underwent surgery after a suppression
      of active inflammation by medical treatment.

PMID- 8741432
TI  - [Surgical treatment of infective endocarditis : an analysis of the risk factor
      for operative mortality].
AB  - From January 1980, through December 1995, 60 patients underwent surgical
      treatment of infective endocarditis (IE) at Sakakibara Hospital. Of 60 patients,
      40 showed active endocarditis and 20 healed endocarditis at the time of
      operation. The over-all hospital mortality was 10% (6/60). The complication of
      cerebral accident (embolism and bleeding) was related to a higher incidence of
      operative mortality. The reconstructions of destruction and disruption of
      ventricular-aortic or mitral-aortic continity in the presence of acute infection
      of the annular tissue were in need of radical and complex surgical techniques. It
      is recommended to follow up these patients thoughtfully and to perform
      reoperation or re-reoperation before a patient develops severe heart failure or
      multiple organ failure.

PMID- 8741433
TI  - [Clinical problems in surgical treatment for active infective endocarditis].
AB  - From October, 1982, to December, 1995, 22 patients with active infective
      endocarditis underwent surgical treatment. Of 22 patients, 12 patients (group P)
      demonstrated microorganisms on blood culture obtained at the operation and/or in
      the excised valve, and 10 patients (group N) showed acute inflammatory reaction
      in the excised valve microscopically. Operative mortality in group P was
      significantly higher than that in group N (50% versus 0%,p < 0.01). Especially in
      group P, five of six patients (83%) with uncontorolled infection for more than
      eight days died within 30 days of operation. This showed that prolonged
      preoperative periods of uncontrolled infection influenced the surgical outcome of
      active infective endocarditis. In conclusion, patients who do not promptly
      response to antibiotic treatment must be considered for early operation within
      seven days of the diagnosis of infective endocarditis to decrease operative
      mortality. The plasma level of CRP and definition of sepsis may be useful as
      indicators of uncontrolled infection.

PMID- 8741434
TI  - [Long-term results and special issues of operation for infective endocarditis].
AB  - Between 1977 and June 1996, 183 patients underwent operation for infective
      endocarditis (IE) at our institution. Long-term mortality and morbidity were
      analyzed according to the STS/AATS guidelines (1988). Operative mortality
      including hospital deaths was 4.9% in all patients. Actuarial survival (including
      all deaths) at 10 postoperative years was 79.6% after AVR (n = 91), 87.9% after
      MVR (n = 40) and 90.0% after DVR (n = 46). There was no significant difference
      among 3 groups. Reoperation free and freedom from all valve-related mortality and
      morbidity at 10 years were 94.0% and 70.4% after AVR, 90.9% and 83.7% after MVR
      and 93.4% and 79.7% after DVR, respectively. And the differences among 3 groups
      were not significant in both freedom proportions. Overall results in this series
      of patients were acceptable. However, several patients with active IE and
      extensive perivalvular abscess were not saved even if translocation method and/or
      other advanced surgical procedures were applied. Introduction of aortic valve
      homografts might be a key factor for successful treatment for patients with
      extensive IE lesion.

PMID- 8741435
TI  - [Early and late results of surgical intervention for 32 active infective
      endocarditis patients in last 10 years].
AB  - Thirty-two active infectious endocarditis patients who underwent 36 surgical
      procedures (23 NVEs, 13 PVEs) in last 10 years were reviewed. Seven patients
      (19.4%) died early postoperatively, 3/23 (13%) in NVEs and 4/13 (31%) in PVEs,
      and the causes of death were LOS in 5, MOF in one and cerebral bleeding in one.
      NVE patients of double valve deterioration who developed cardiogenic shock had
      poor operative results, 3 death in 4 (75%) despite of circulatory assist. Aortic
      PVEs who underwent Danielson's translocation technique also showed 3 death in 4
      (75%). Five in 25 survivors (20%) developed late death and 3 of them were related
      with reinfection of prosthetic valve. We concluded that surgical treatment for
      active IE provides reasonable results, although they are still challenging for
      double valve NVEs and aortic PVEs, for which aortic root replacement using
      homograft would be the procedure of choice.

PMID- 8741436
TI  - [Surgical treatment of infective endocarditis].
AB  - From 1981 to 1996, 48 consecutive patients, aged range 1 to 72 years, underwent
      surgical treatment for infective endocarditis. The infection was in the aortic
      valve in 10 patients, the mitral valve in 17, the aortic and mitral valves in 7,
      mixed aortic, mitral and tricuspid valves in one, the tricuspid valve in 9, the
      pulmonary valve in 3, and the other in 2, thirty-seven patients had native valve
      endocarditis (NVE) of which 22 cases were in the active stage. Seven cases had
      active prosthetic valve endocarditis (PVE) and 4 had VSD patch infection. The
      overall hospital mortality rate was 14.6% (7/48). The hospital mortality rate of
      NVE was 2.7% (1/37) and that of active NVE was 4.5% (1/22). That of PVE was 71.4%
      (5/7) and one of 4 cases with VSD patch infection was lost, so the mortality rate
      of the prosthetic material infection was 54.5% (6/11). Only 1 patient required
      reoperation for persistent infection. There were 2 late deaths caused by
      noncardiac disease. Thirty-nine of the total IE patients are now survived. These
      data demonstrate excellent results in patient with NVE undergoing the surgical
      treatment at the early phase, and support the premise that patients with active
      PVE should have also early surgical intervention.

PMID- 8741437
TI  - [Surgical treatment for active infective endocarditis : septic embolization and
      mycotic aneurysms].
AB  - From 1978 through 1995, surgical treatment for active infective endocarditis
      (native valve) was performed in 17 patients. The indication for operation at the
      active phase was progressive heart failure in 5 (A-group) and uncontrolled
      infection in 12 (B-group). Operative findings showed vegetations in all cases,
      perforations of the valve in 6, rupture of tendon in 2, and annular abscesses in
      2. One patient in B-group died 14 days after the operation with postoperative
      mediastinitis and sepsis. There was no perioperative complications in A-group. In
      B-group before operations 8 patients (66.7%) has an embolic event before
      operations. The anatomic sites of embolization were the central nervous system (3
      patients), viscera (2 patient) and peripheral arteries (3 patients). And after
      operation there were 2 mycotic aneurysms of the hepatic artery and the popliteal
      artery, and 1 pyogenic spondylitis. We conclude that the risk of embolization is
      high in patients undergoing surgery at active phase of infective endocarditis
      because of uncontrolled infection ; thus, such patients should be carefully
      monitored for emboli and mycotic aneurysms.

PMID- 8741438
TI  - [Surgical-treatment for active infective endocarditis].
AB  - The results of surgical treatment of active native infective endocarditis in 24
      patients were analyzed. Fifteen of 24 (63%) patients were successfully cured by
      operation. Three of the 8 patients with severe cardiac failure who underwent
      emergency operation died of low cardiac output syndrome and bleeding early
      postoperatively. One of the 6 patients with late death had preoperative cerebral
      embolism and died of multiple organ failure. Five of them had annular infection.
      Among 6 patients with annular infection, 3 patients who had Staphylococcus
      epidermidis and Gram negative bacterium as a causative microorganism had a short
      duration within 4 weeks from the onset to operation. Two died suddenly in the
      long-term period after surgery because of prosthetic valve detachment. The second
      operation were required for other 4 patients because of prosthetic valve
      endocarditis or perivalvular leakage. Three of them were lost from low cardiac
      output syndrome. These findings suggested that delayed surgical intervention may
      be a major causative factor resulting in high surgical mortality. For patients
      with active native infective endocarditis, an early aggressive operation should
      be considered prior to congestive heart failure and the destruction of the
      annulus.

PMID- 8741439
TI  - [Surgical treatment for active infective endocarditis].
AB  - Between April 1975 and December 1995, 33 patients with active infective
      endocarditis underwent surgical treatment at our hospital. The location of
      diseased valve was shown as ; 18 in aortic, 11 in mitral, and 4 in aortic and
      mitral position. Of these, 14 patients had an annular abscess or mycotic
      aneurysm. All patients achieved antibiotic therapy previously, and predominant
      indication for operation was congestive heart failure. All patients underwent
      valve replacement. The reconstructive procedures for 14 patients with
      paravalvular involvement were as follows ; direct closure : 5 cases, direct
      closure+tilted prosthesis technique : 5 cases, and another 4 cases were, patch
      closure of VSP resulting from a septal abscess, patch closure+translocation,
      translocation, and reconstruction of annulas with pericardial patch. There were
      five (15.2%) operative and hospital deaths and actuarial survival rate was 81%
      and 61% at 5 and 10 years after operation. Including one who died early after
      operation, there were 5 cases with postoperative paravalvular leakage and its
      main cause were persistent infection. In conclusion, it considered that the
      principles of treating active infective endocarditis is to decide the optimal
      timing for operation, debride the infected tissue, and close the defect
      completely.

PMID- 8741440
TI  - [Clinical activity of native valve endocarditis].
AB  - We reviewed clinical course and surgical outcome of 31 patients with native valve
      endocarditis who underwent an operation between 1980 and 1994. In the present
      study, 15 patients who manifested a neurologic complication associated with
      endocarditis and/or those who had a periannular abscess were assigned as
      'clinical active'. Comparing with non-active group (n = 16), clinical active
      group included more patients with increased C-reactive protein level and those
      with histological acute inflammatory reaction on excised valvular tissue. Optimal
      timing of the operation and surgical procedures for aortic root reconstruction
      were significant problems in the active group. Actuarial probability of survival
      at 5 postoperative year was 50.8 and 87.5% in the active and non-active group,
      respectively. The results suggest our 'clinical activity' is a useful predictor
      in patients with native valve endocarditis.

PMID- 8741441
TI  - [Surgical treatment of active infective endocarditis].
AB  - Between August 1980 and December 1995, 29 patients have undergone valve
      replacement for active infective endocarditis (IE) at our institute. Twenty five
      patients had native valve endocarditis (NVE) and 4 had prosthetic valve
      endocarditis (PVE). The indication for surgery in 29 patients was congestive
      heart failure, septicemia or systemic embolization. Twenty six patients had
      vegetation. Eleven patients had AVRs, including one modified Bentall operation,
      10 had MVRs and four had DVRs with mechanical prosthetic valve. There were eleven
      early death (38%) and one late death. Operative mortality rate has reduced to 24%
      after 1991. We conclude that early surgical intervention should be taken
      according to the hemodynamic state of the patients irrespective of the presence
      of septicemia.

PMID- 8741442
TI  - [Two cases of Aspergillus endocarditis after cardiac surgery in childhood].
AB  - Aspergillus endocarditis has been considered as a fatal disease because of the
      difficulty of diagnosis and treatment. Two cases of Aspergillus endocarditis
      after congenital cardiac surgery are reported. One case was 5-year-old boy after
      patch closure of atrial septal defect and enlargement of porcine-pericardial
      patch to pulmonary arterial stenosis. Pulmonary arterial patch infection with
      vegetation occurred 13 months after operation, and he underwent pulmonary
      arterial reconstruction with E-PTFE patch after complete removal of porcine
      pericardial patch. The other case was 5 year-old girl after repair of tetralogy
      of Fallot with autologus pericardial monocusp patch. Right ventricular outflow
      patch infection and mediastinitis occurred 14 months after operation. Although
      three times of the patch exchange, patch infection relapsed. Therefore, she
      underwent thorough curettage of infected tissue, and extra-anatomical bypass to
      bilateral pulmonary artery from right ventricle with E-PTFE Y-graft. The relapse
      of endocarditis has not been recognized after these surgical treatments in both
      patients.

PMID- 8741443
TI  - [A case report of active infectious endocarditis caused by MRSA with chronic
      renal failure].
AB  - A 62-year-old female, who had chronic renal failure treated by HD, was admitted
      to our hospital with fever. MRSA was identified by blood culture examination.
      Echocardiography revealed vegetations attached to the mitral valve. Mitral
      abscess was detected during operation. Mitral valve replacement was performed. We
      used ECUM and HD for the chronic renal failure during peri- and postoperative
      days. The postoperative clinical course was uneventful.

PMID- 8741444
TI  - [A case report of an infective endocarditis caused by methicillin-resistant
      Staphylococcus aureus with successful mitral valve replacement].
AB  - We report a case of successful mitral valve replacement performed on the patient
      who is an infective endocarditis due to MRSA. She was 27-year-old female and
      treated by antibiotics medication because of remittent fever two years ago. On
      August 1995, cerebral infarction occurred and she was pointed out endocarditis.
      After high fever continued, blood cultures demonstrated MRSA. Furthermore,
      echocardiography showed vegetation on posterior mitral valve leaflet and moderate
      mitral regurgitation so, mitral valve replacement with a S.J.M. 25 mm performed
      to control MRSA sepsis condition. During operation, we used VCM 2 g into the
      extracorporeal circulation and after operation 0.5 g intravenously every 6 hours.
      Two weeks later we changed antibiotics to FOM, Viccillin and ABK according to the
      result of minimum inhibitory concentration (MIC) obtained through blood culture.
      The patient was discharged on the 44 th postoperative day because of her
      uneventful postoperative course.

PMID- 8741445
TI  - [A case of aortic valve replacement for active infectious endocarditis with multi
      organ failure preoperatively].
AB  - A 57-year-old man underwent aortic valve replacement for active infectious
      endocarditis with multi-organ failure. He had become unconscious suddenly and had
      undergone transient pacing and endoteacheal intubation in the first hospital.
      Then he had been transferred to the second hospital, where careful medical
      treatment had been done for cardiac and hepatorenal failure. When he was
      transferred to our hospital, he was in New York Heart Association functional
      class IV with catecholamine support and had acute renal failure required
      hemodialysis. Aortic valve replacement with bileaflet mechanical valve and direct
      closure of perivalvular ring abscess made the patient free from catecholamine
      support and hemodialysis, while he needed permanent pacemaker implantation. This
      case suggests that both careful medical treatment before surgery and timing of
      surgical intervention were important for active infectious endocarditis with
      multi-organ failure preoperatively.

PMID- 8741446
TI  - [A case report of aortic root replacement with fresh aortic homograft for valve
      detachment due infective endocarditis].
AB  - A 28-year-old male received a redo aortic valve replacement (AVR) with a 19 mm
      St. Jude Medical mechanical valve 3 months after the initial AVR because of
      recurrent valve detachment. We re-operated on this patient by aortic root
      replacement using a fresh aortic homograft. The donor of the homograft was a 59
      year-old female who died of a traffic accident. The aortic root and valve was
      harvested aseptically and stored in a nutrient medium including antibiotics at 4
      degrees C for 4 days. At the 3rd operation, aortico-ventricular discontinuity and
      an annular-abcess-like cavity were found. After debridement, the cavity was
      closed with a homograft aortic wall and then aortic root replacement was
      performed using a fresh aortic homograft. At first, prosthetic valve detachment
      seemed to be caused by infective endocarditis on the basis of his clinical
      history. However, causative organisms had never been recovered from the blood or
      the specimens obtained at the time of operation and reoperation. Post-operative
      HLA examination revealed No. 51 on HLA-B locus and thus we suspected that valve
      detachment might have been due to inflammation of the aortic wall caused by a
      subtype of Behcet disease. The early post-operative course was uneventful with a
      low dose of predonine. Post-operative aortography showed no aortic regurgitation
      and normal coronary anastomosis. Unfortunately however, he died suddenly 8 months
      after the operation. Autopsy demonstrated the presence of aortic wall necrosis
      with massive infiltration of macrophages and leucocytes resulting in dehiscence
      of the coronary anastomotic site. The cause of homograft detachment could not be
      determined for sure but might be recurrent infective endocarditis, although
      causative organisms were never identified, or infective endocarditis in
      combination with Behcet vasculopathy.

PMID- 8741447
TI  - [Successful redo-AVR with cryopreserved allograft for prosthetic valve
      endocarditis : report of a case].
AB  - A 20-year-old male undergoing mechanical aortic valve replacement suffered from
      prosthetic valve endocarditis by Coagulase negative Staphylococci 3 months
      postoperatively. Echocardiography revealed left ventricular distention, severe
      paravalvular leakage, valve detachment and large periannular abscess adjacent to
      the left main coronary artery. Redo-AVR was successfully performed with a
      cryopreserved aortic allograft by cylinder technique. The orifice of abscess was
      covered with the aortic wall of the graft. Postoperative echocardiography showed
      trivial central regurgitation and the abscess cavity went on vanishing. He
      discharged from hospital 2 months later without any symptom.

PMID- 8741448
TI  - [Maze operation for chronic atrial fibrillation with valvular heart diseases].
AB  - Between July 1994 and August 1995, 14 patients underwent combined modified maze
      procedure and valvular surgery including 5 patients having reoperation.
      Associated procedures were performed with mitral valve operation (n = 13),
      tricuspid annuloplasty or valve replacement (n = 9) and aortic valve replacement
      (n = 4). Duration of atrial fibrillation (AF) varied from 1 to 18 years (mean 8.0
      +/- 5.8 year), the f-wave voltage ranged from 0.05 to 0.5 mV (0.21 +/- 0.13 mV),
      left atrial dimension (LAD) ranged from 35.6 to 66.3 mm (49.0 +/- 9.3). One
      patient died 2 months after undergoing combined maze procedure and MVR + TAP due
      to pulmonary infection and sepsis, but the other 13 patients survived. Nine
      patients (69%) regained atrial rhythm, two patients (15%) had junctional rhythm
      and another two (15%) remained in AF at follow-up periods between 1 to 11.5
      months (6.3 +/- 3.1). The nine patients who recovered to normal sinus rhythm had
      preoperative f-wave for a significant higher voltage than the patients with AF
      and JR (0.27 +/- 0.12 vs 0.13 +/- 0.05 mV, p < 0.05) and a smaller left atrial
      dimension (44.5 +/- 0.7 vs 54.8 +/- 6.9 mm, p < 0.05). These data suggest that
      the maze operation is effective and should be considered for patients with
      chronic AF indicated for surgical valvular diseases.

PMID- 8741449
TI  - [Influence of recirculation type blood cardioplegia on perfusion pressure in open
      heart surgery].
AB  - Infusion blood cardioplegia often decreases the perfusion pressure during open
      heart surgery. The blood level of bradykinin (BK) was measured in both the
      cardiopulmonary bypass (CPB) and blood cardioplegia circuit. Infusion
      cardioplegia with recirculation type circuit increased the BK level of
      cardioplegia and the perfusion pressure decreased abruptly with the increase BK
      level in the CPB circuit. In the case of single pass type circuit the BK level
      was not increased either in cardioplegia or CPB and perfusion pressure was not
      decreased. We concluded that the single pass type of cardioplegia circuit is
      superior to the recirculation type because of less production of BK.

PMID- 8741450
TI  - [Postoperative early complication of primary lung cancer].
AB  - We analyzed postoperative early complications of primary lung cancer in 321 cases
      during 1982 to 1993 in our hospital, and assessed the prevention and the
      treatment against these complications. In order of frequency the complications
      are, paroxymal supraventricular tachcarida (10.6%), atelectasis due to sputum
      (6.9%), pulmonary fistula for more than seven days (4.7%), hoarseness of voice
      due to recurrent nerve palsy (4.0%), chylothorax (2.5%), gastrointestinal tract
      complications (2.2%), reoperation due to massive bleeding (1.2%), wound
      dehiscence (0.9%), bronchial fistula (0.6%), rupture of ascending aorta (0.3%)
      and myocardial infarction (0.3%). The two cases of bronchial fistula after
      pneumonectomy, and one of myocardial infarction after lobectomy through the
      median approach died of early complications. The operative indication for primary
      lung cancer is extended to the patients with higher age and lower pulmonary
      function; so we should be careful for the pre and postoperative prevention and
      the rapid and appropriate treatment against these postoperative early
      complications.

PMID- 8741451
TI  - [A case of contralateral pneumothorax after right pneumonectomy].
AB  - A 46-year old man, who had a history of right pneumonectomy for pulmonary
      tuberculosis 28 years ago, was referred to our hospital for surgical treatment of
      contralateral pneumothorax. The patient underwent multiple excisions of bullae
      and parietal pleurectomy through the median sternotomy in order to save pulmonary
      function. The postoperative course was satisfactory as he could maintain
      preoperative pulmonary function. He returned to his work soon. We consider that
      the median sternotomy would be the most useful approach to save pulmonary
      function of patients who plan to undergo surgical treatment of contralateral
      pneumothorax after pneumonectomy.

PMID- 8741452
TI  - [Inhaled nitric oxide for postoperative pulmonary hypertensive crisis in a
      patient with complete atrioventricular canal associated with Down's syndrome: a
      case report].
AB  - Two-year-old boy with Down's syndrome was treated with inhaled nitric oxide for
      pulmonary hypertensive crisis after correction of complete atrioventricular canal
      and persistent ductus arteriosus. The acute rise in pulmonary pressure and
      hemodynamic instability occurred on 3rd, 4th and 6th post operative days and
      pulmonary vasodilation with prostaglandin E1 and amrinone had failed. Twenty ppm
      of inhaled nitric oxide effectively reduced the pulmonary pressure and the
      patient was subsequently weaned from ventilation. Inhaled nitric oxide exerted a
      pulmonary vasodilation without decreasing systemic pressure in this patient with
      postoperative pulmonary hypertensive crisis.

PMID- 8741453
TI  - [Long-term results of emergency coronary artery bypass grafting].
AB  - During a 20-year period, 364 patients underwent coronary artery bypass grafting
      (CABG) for the treatment of ischemic heart disease. Among these patients, 28
      underwent emergency surgery. The reasons for performing emergency CABG were
      unstable angina in 15 patients, impending myocardial infarction in 12 patients,
      and congestive heart failure in 1 patient. Eleven patients died postoperatively.
      Eight variables were examined by univariate analysis for their influence on the
      occurrence of a hospital death. IABP and acute coronary occlusion were found to
      be predictors of hospital death and previous myocardial infarction was a
      predictor of hospital survival. Seventeen patients were followed up for 12 years.
      There was no cardiac death and actuarial survival at 12 years was 63%. The 14
      survivors are now in NYHA functional class I or II. Although the operative
      mortality rate is high after emergency CABG, the patient's prognosis is good.

PMID- 8741454
TI  - [The combined resection of left atrium for advanced lung cancer on
      cardiopulmonary bypass: a case report].
AB  - We successfully treated surgically using cardiopulmonary bypass an elderly
      patient, a seventy-six-year-old man, with primary advanced lung cancer (rt. S6)
      with left atrial extension. He had intermittent episodes of bloody sputum. A
      preoperative chest roentogenogram revealed an abnormal mass shadow in S6 of the
      right lower lobe of the lung. MRI findings of the chest and a right heart
      catheterization with levophase demonstrated the extension of the tumor into the
      left atrium. A distant metastatic work-up was negative. By use of the full
      lateral thoracotomy and cardiopulmonary bypass, the tumor was removed en bloc
      through a combined left atrial resection and right middle and lower lobectomy.
      The patient has been well without and symptoms 8 months after surgery. An
      advanced lung cancer invading the left atrium can be safety and completely
      resected with the use of cardiopulmonary bypass if the extent of left atrial
      involvement is recognized preoperatively.

PMID- 8741455
TI  - [Early and late results of pericardiectomy for constrictive pericarditis].
AB  - Seven patients (4 males and 3 females: age 1 to 71 years old) who underwent
      operations for constrictive pericarditis from 1980 were reviewed. The median
      sternotomy approach was used without cardiopulmonary bypass. The pericardial flap
      was excised just anterior to both phrenic nerves. The postoperative hemodynamic
      improvement was good, especially in cardiac index (from 2.30 to 3.30 l/min/m2).
      Two patients were operative death. One was metastasis to pericardium from gastric
      cancer and another was multiple organ failure due to sepsis. Long-term survival
      was 3 to 13 years. One patient was dead at nine years after operation. Others
      were in New York Heart Association Class 1 or 2 in the long-term period after
      surgery. We conclude that our method can lead to good cardiac functional results
      and long-term good results. Our report wishes to emphasize early diagnosis and
      operation.

PMID- 8741456
TI  - [Simultaneous surgical revascularization for myocardial and peripheral vascular
      ischemia].
AB  - Patients with vascular disease has a high incidence of coexistence of coronary
      artery disease and patients with coronary artery disease can be associated with
      aortic or peripheral vascular occulusive lesions. Simultaneous coronary artery
      bypass grafting (CABG) and surgery for coexistent vascular lesions was performed
      in 13 patients from October 1991 until September 1995. Average number of graft
      for CABG was 3.5. For vascular lesions, fomoro-popliteal artery bypass was
      performed on four patients, aorto-both side iliac artery bypass using bifurcated
      prosthesis on there, aorto-iliac artery bypass on one, carotid endarterectomy on
      three and aorto-subclavian artery bypass on two patients. All patients survived
      without any major complications. There were no late death noted in the longest
      follow-up period of 42 months. Simultaneous surgical procedures for coronary
      arterial and other vascular lesions can be performed with acceptable risk and may
      offer physiological, psychological, social and echonomical advantages to avoid
      rehospitalization and repeated surgical interventions.

PMID- 8741457
TI  - [A case of effusive-constrictive pericarditis and its surgical treatment].
AB  - A 69-year-old male of effusive-constrictive pericarditis with a symptom of right
      heart failure was reported. The patient underwent surgery, as the medical
      treatment had not been effective. Through median spritting, very thickened
      pericardium and calcified epicardium of the right atrium, the right ventricle and
      the left ventricle were resected as largely as possible. In the space between the
      pericardium and epicardium, there existed yellow and thick fluid of about 50 ml
      which was evacuated. After surgery hemodynamic improvement was observed and the
      patient experienced a smooth postoperative course. Although pathological
      examinations revealed no special findings except the increased activity of
      adenosine deaminase of the yellow and thick fluid, tuberculosis was mostly
      suspected as the cause of the disease.

PMID- 8741458
TI  - [An aged case of successful repair for the ruptured distal aortic arch aneurysm
      associated with aortic regurgitation: a case report].
AB  - Ruptured thoracic aortic aneurysm had severely high mortality. A 83-year-old
      female, who had suddenly complained back pain and been diagnosed as the ruptured
      distal aortic arch aneurysm with aortic regurgitation by computer tomography and
      echo cardiogram, was admitted for an emergent surgery. Aortic arch replacement
      and aortic valve replacement were performed through median sternotomy under deep
      hypothermic circulatory arrest with the retrograde cerebral perfusion. She was
      complicated with respiratory ventilation failure due to the massive mediastinal
      hematoma and her chest was kept open postoperatively. Her chest was closed two
      days after the first operation and she recovered uneventfully.

PMID- 8741459
TI  - [Constrictive pericarditis with dissecting aortic aneurysm (DeBakey type II)].
AB  - We experienced a case of constrictive pericarditis with dissecting aortic
      aneurysm (DeBakey type II). The patient complained of orthopnea and leg edema.
      The cause of constrictive pericarditis was pericardial effusion due to dissecting
      aortic aneurysm. Ascending aortic replacement with graft and decortication of
      thickened pericardium were performed. We confirmed the decrease of CVP and PAP
      intraoperatively. Postoperative course was uneventful.

PMID- 8741460
TI  - [Two cases of mitral stenosis associated with ball thrombus in the left atrium].
AB  - Two patients (55-year-old female and 77-year-old female) were operated on for
      mitral stenosis associated with left atrial ball thrombus. The first case had the
      episode of cerebral infarction and second case had syncopal attack. Both of them
      presented with systemic arterial embolism. After confirmation of the diagnosis by
      echocardiography, removal of ball thrombi, OMC and MVR were carried out urgently.
      Considering high risk of "hole in one sudden death" and multiple-episodes of
      systemic embolization, ball thrombus should be removed as urgent following
      confirmation of diagnosis.

PMID- 8741461
TI  - [Successful repair of right atrial rupture due to nonpenetrating trauma of the
      chest].
AB  - A 24-year-old male was brought to our hospital after being injured in a traffic
      accident. On arrival, his blood pressure was 70/44 mmHg and his pulse rate was
      135/min and regular. Chest X-p revealed cardiomegaly but there was no pleural
      effusion or bone fracture. Echocardiogram revealed cardiac tamponade and he was
      diagnosed as cardiac rupture due to non penetrating trauma. Under midline
      sternotomy, right atrial rupture was repaired. The patient developed cardiac
      arrest lasting approximately 8 minutes during anesthetic induction, so he needed
      to be ventilated for 8 days. However his postoperative course was not so eventful
      and he was discharged 38 days after surgery without any neurophysiological
      disturbance.

PMID- 8741462
TI  - [Systemic-to-pulmonary artery shunt using the internal thoracic artery].
AB  - Systemic-to-pulmonary artery shunts may be useful for palliation of cyanotic
      congenital heart disease. We report the two cases of a 2-year-girl and a 5-year
      girl in whom the internal thoracic artery was used to create a systemic-to
      pulmonary artery shunt. This technic may have distinct advantages in selected
      cases and should be considered as an alternative during investigation of the
      older child who requires a systemic-to-pulmonary shunt.

PMID- 8741463
TI  - [Surgery for aortic valvular disease with congenital quadricuspid aortic valve].
AB  - A case of quadricuspid aortic valve is reported. A 69-year-old man was
      hospitalized with chest oppression at rest and abnormal electrocardiogram and
      diagnosed aortic regurgitation by echocardiography and aortic angiography. Aortic
      regurgitation was grade III according to Seller. Aortic valve replacement was
      performed successfully with a 21 mm St. Jude Medical valve. The aortic valve
      showed four cusps consisting of two equal larger cusps and two equal smaller
      cusps which was type C according to Hurwitz. Each valve was thickened and
      adhered, and fenestrations were found at each commissure. The right coronary
      ostium was small but not displaced. Twenty five cases in literature which were
      corrected surgically are also reviewed. Quadricuspid aortic valve is a rare
      anomaly but must be considered as a malformation which leads to severe valve
      failure in later life.

PMID- 8741464
TI  - [A case of carcinoid tumor of left superior trunk treated by sleeve upper
      lobectomy].
AB  - A case of bronchial carcinoid was reported. A 39-year-old male was suffered from
      recurrent pneumonia. Bronchofiberscopy revealed a polipoid tumor nearly
      obstructing left superior bronchial trunk. CT scan showed a round tumor about 1
      cm in diameter. Resection of the tumor was carried out by sleeve upper lobe
      loectomy. Histological diagnosis was typical carcinoid, and there was no lymph
      node matastasis. Postoperative course was uneventful. Granulation and stenosis
      were not observed at the part of anastomosis.

PMID- 8741465
TI  - [Intracavity suction and drainage in a patient with giant bulla accompanied by
      pneumoconiosis and emphysema: a case report].
AB  - A 74-year-old man with giant bulla accompanied by pneumoconiosis and emphysema
      was treated by intracavity suction and drainage procedure using chemical irritant
      and fibrin glue. About one month later, the bulla disappeared and the patient
      symptomatically improved on discharge from hospital. Intracavity suction and
      drainage is safe and effective treatment of emphysematous bulla in patients
      considered to be a bad risk for formal thoracotomy.

PMID- 8741466
TI  - [Surgical treatment to the lung cancer in a patient receiving hemodialysis].
AB  - We performed right lower lobectomy for lung cancer in a 62-year-old man who had
      been under hemodialysis for 4 years. During the operation, hyperkalemia occurred
      and was treated by GI therapy (continuous intravenous infusion of glucose +
      insulin). On the 3rd postoperative day, CVP was increased and hypotension
      occurred during hemodialysis. It was considered that heart failure had developed.
      Attention to the possibility of heart failure is important in the postoperative
      management of patient on chronic hemodialysis who require lung resection. He was
      discharged without bleeding of infection. There have been few reports on
      operations for lung cancer in such patients, so our experience is significant.

PMID- 8741467
TI  - [A case report of relapsed esophageal cancer with tracheal stenosis treated with
      expandable metallic stent placement].
AB  - A 63-year-old male who suffered from relapsed esophageal cancer in the thoracic
      lymphonode causing severe tracheal stenosis, was treated by expandable metallic
      stent (EMS) placement. Dyspnea has disappeared immediately after EMS placement
      and the patient has been free from dyspnea until his death. EMS has been very
      effective for the therapy of tracheal stenosis by esophageal cancer.

PMID- 8741468
TI  - [Thermoregulatory research in the field of anesthesia and intensive care: a
      review].
AB  - Most general anesthetics, opioids, sedatives and local anesthetics perturb
      thermoregulatory responses. Accordingly the core temperatures triggering
      sweating, thermoregulatory vasoconstriction and shivering are varied in
      perioperative periods. Redistribution hypothermia is a quite common phenomenon
      during not only general anesthesia but epidural/spinal anesthesia. Maintenance of
      core temperature after redistribution hypothermia is achieved by the effective
      vasoconstriction which prevents heat loss from the skin surface. Deliberate mild
      hypothermia is effective for brain protection during neurosurgery and ischemic
      episode. However, obtaining effective decrease of core temperature is sometimes
      difficult because of thermoregulatory vasoconstriction. Subsequently,
      vasodilation therapy with appropriate drugs is now under investigation.
      Hypothermia per se causes critical complications in patients, and the maintenance
      and warming method to maintain normothermia is important in perioperative period.

PMID- 8741469
TI  - [Intraoperative continuous epidural block influences postoperative changes in
      breathing pattern and thoracoabdominal movement associated with upper abdominal
      surgery].
AB  - We have examined the changes in breathing pattern and thoracoabdominal movement
      associated with upper abdominal surgery in order to evaluate the possible
      influences of nociceptive input on respiration. Sixteen patients scheduled for
      gastrectomy were studied. Continuous epidural block was instituted prior to the
      induction of anesthesia and maintained throughout the surgery in 8 of 16 patients
      (Group 1) while it was instituted upon the peritoneal closure and maintained
      thereafter in the remaining 8 patients (Group 2). Breathing pattern and
      thoracoabdominal motion were determined before and after surgery while the
      patients awake by respiratory inductance plethysmography (Respisomnography, Chest
      MI). Breathing frequency and minute ventilation increased significantly while
      tidal volume was unchanged after the operation regardless of the intraoperative
      epidural block. Furthermore, there were identical shortening of inspiratory time
      and prolongation of duty ratio (inspiratory time/duration of a breath) in the two
      groups. Contribution of rib cage movement on tidal volume increased significantly
      postoperatively in all the patients. However, the changes were significantly
      smaller in patients receiving intraoperative epidural block. These results
      indicate that the causes of tachypnea and increased minute ventilation are
      different from the mechanism responsible for the alteration of thoracoabdominal
      partitioning of ventilation after upper abdominal surgery. The former may be
      related to the metabolic changes and, conceivably, unaffected by continuous
      epidural block. While the latter may be the consequence of the reflex inhibition
      of the diaphragmatic function that can be, at least partially, modified by
      continuous epidural block.

PMID- 8741470
TI  - [Sevoflurane comparably decreases the threshold for thermoregulatory
      vasoconstriction as isoflurane].
AB  - The core temperature triggering thermoregulatory arteriovenous shunt constriction
      is defined as the threshold for vasoconstriction. Vasoconstriction helps prevent
      further core hypothermia by decreasing cutaneous heat loss and constraining
      metabolic heat to the core thermal compartment. A previous study showed
      isoflurane inhibited thermoregulatory threshold. However there is no study to
      confirm whether sevoflurane perturb thermoregulatory vasoconstriction or not.
      Consequently we tested the hypothesis that 1.0 minimum alveolar concentration
      (MAC) sevoflurane and 1.0 MAC isoflurane would reduce the vasoconstriction
      threshold comparably. With institutional review board approval, we studied 20
      patients, aged 20-60 yr, undergoing open abdominal surgery. No premedication was
      given. Ten patients each were anesthetized with 1.0 MAC sevoflurane (2.0%) alone
      or 1.0 MAC isoflurane (1.2%) alone. A forearm minus fingertip, skin temperature
      gradient 0 degree C was considered to demonstrate significant vasoconstriction;
      the esophageal temperature triggering vasoconstriction identified the threshold.
      Morphometric characteristics were comparable in each group. The threshold for
      vasoconstriction was 35.1 +/- 0.4 degrees C in the patients given 1.0 MAC
      sevoflurane, which was comparable that in those given 1.0 MAC isoflurane: 35.3 +/
      0.7 degrees C. We thus conclude that sevoflurane impairs thermoregulation
      comparably with isoflurane.

PMID- 8741471
TI  - [Hepatic blood flow decreases during laparoscopic cholecystectomy].
AB  - Changes of median hepatic venous blood flow (MHVBF) and left portal venous blood
      flow (Lt. PVBF) were measured continuously in 31 patients undergoing elective
      laparoscopic cholecystectomy (LC) by using transesophageal echocardiography
      (TEE). The patients were anesthetized with inhalation and epidural anesthesia.
      MHVBF and Lt. PVBF decreased from preoperative level of 317 +/- 61 ml.min-1, 522
      +/- 86 ml.min-1 to 73 +/- 22 ml.min-1, 98 +/- 28 ml.min-1 after inflation with
      high pneumoperitoneum pressure and they recovered by deflation. These findings
      suggest that hepatic blood flow decreases by increased intraperitoneal pressure.

PMID- 8741472
TI  - [Effects of halothane, isoflurane, enflurane, and sevoflurane on the monosynaptic
      reflex response in the isolated spinal cord of newborn rats].
AB  - Monosynaptic reflex responses (MSRs) in the isolated spinal cord of newborn rats
      were elicited in the ventral root by stimulation of the ipsilateral dorsal root.
      MSRs were considered to be mediated by non-NMDA class glutamate receptors. We
      studied the depressant effects of halothane, isoflurane, enflurane, and
      sevoflurane on MSR amplitudes as a function of anesthetic concentration comparing
      with MAC value of each anesthetics. The spinal cord of newborn rats were rapidly
      dissected out, and placed in a chamber superfused with artificial cerebrospinal
      fluid (ACSF, pH 7.4, 34 degrees C) equilibrated with 95% O2 - 5% CO2. Anesthetic
      gases were delivered with specific vaporizers and bubbled in the ACSF. Each
      anesthetic concentration was determined by gas chromatography. Either of the
      anesthetics reversibly depressed MSR amplitudes in a concentration dependent
      fashion. Concentration-response curves for MSR amplitudes were constructed and
      the concentrations which produced a half-maximum inhibition (IC50) were 0.56,
      0.65, 0.97 and 1.18 mM for halothane, isoflurane, enflurane, and sevoflurane,
      respectively. These IC50 values correlated well with those of MAC values (r =
      0.999, P < 0.001) obtained from adult rats in an in vivo condition. The MSR
      response in the isolated spinal cord of newborn rats is considered as a useful
      model for analysis of potency of volatile anesthetics.

PMID- 8741473
TI  - [Usefulness of NODSS (nasal/oral discriminate sampling system) in end-tidal
      carbon dioxide gas monitoring].
AB  - We investigated the usefulness of nasal/oral discriminate sampling system (NODSS)
      that had been developed recently in order to obtain the accurate end-tidal carbon
      dioxide (PET(CO2)) from a spontaneously breathing patient through a nomal airway.
      Fifty patients were monitored using a capnograph with NODSS following extubation
      in the postanesthesia unit. PET(CO2) data were collected by means of nasal, oral
      or nasal/oral sampling. The levels of arterial carbon dioxide (PaCO2) were
      determined simultaneously. In addition to examining the correlation between
      PET(CO2) and PaCO2, we investigated the influence of method of anesthesia, age
      and respiratory rate on the (PaCO2 - PET(CO2)) gradient. In most patients without
      nasal obstruction breathing through the nostril, PET(CO2) determined by selective
      nasal sampling was closer to PaCO2 than those by oral or nasal/oral sampling.
      Furthermore, the mean (PaCO2 - PET(CO2)) gradient was 4.98 mmHg in patients aged
      over 60, while it was 2.02 mmHg in patients aged under 60, suggesting that
      PET(CO2) could not be a good index in elderly people. There was no significant
      difference in the mean (PaCO2 - PET(CO2)) gradient among different methods of
      anesthesia. In conclusion, NODSS was useful in determining PET(CO2) more
      accurately and estimating PaCO2 precisely when used in relatively young people by
      selective nasal or oral sampling.

PMID- 8741474
TI  - [Electrophysiological examinations in Bell's palsy using electroneuronography and
      strength-duration curve].
AB  - In 30 patients with Bell's palsy electroneuronography (ENoG) and strength
      duration curve (S-D curve) were used to evaluate the recovery from the palsy at
      the orbicularis oris and the oculi muscles. At the orbicularis oris muscle, the
      final outcome was poor in the patients in whom minimum ENoG < 10%, and all the
      patients with 30% <or= minENoG showed good recovery. In the patients with 10 <or=
      minENoG < 30, when S-D curve was without scale out, all the patients showed
      complete recovery. The recovery in the orbicularis oculi muscle of the patients
      with minENoG < 10% was all poor, but two patients with 30% <or= minENoG, remained
      in the impaired situation, and one patient with 10 <or= minENoG < 30, without
      scale out in S-D curve showed poor recovery. These findings suggests that
      electrophysiological examinations using ENoG and S-D curve in the patients with
      Bell's palsy can provide valuable information at the orbicularis oris muscle, but
      at the orbicularis oculi muscle, these are less reliable.

PMID- 8741475
TI  - [Neurologic sequelae of spinal anesthesia: local anesthetic toxicity].
AB  - Recent reports of cauda equina syndrome following continuous spinal anesthesia
      have generated concern regarding the safety of not only this particular technique
      but also of the local anesthetic agent itself. This concern has been reinforced
      by data suggesting that similar injuries have occurred with repeated injection
      after a "failed spinal", and by reports of transient radicular irritation
      following single subarachnoid injection. This paper summarizes the above cases
      and reviews recent experiments performed to determine the mechanisms underlying
      local anesthetic toxicity and the factors that contribute to injury. These
      experiments suggest that the recent injuries resulted from a direct effect of the
      local anesthetic and that anesthetic-induced impairment does not result from
      blockade of the sodium channel, per se. These experiments also suggest that
      development of a safer anesthetic is a realistic goal.

PMID- 8741476
TI  - [Transesophageal echocardiography (Part 2): Basic concepts in Doppler
      techniques].
AB  - Cardiac Doppler techniques provide information on blood flow dynamics by applying
      Doppler frequency shift analysis to echo signals from moving red blood cells.
      Velocity and direction of blood flow can be determined and instantaneously
      displayed on a monitor screen. These techniques include pulsed-wave Doppler
      (PWD), continuous wave Doppler (CWD) and color Doppler imaging (CDI). In PWD,
      short bursts of ultrasound waves are emitted at a pulse-repetition frequency
      (PRF), and velocity and direction of blood flow can be measured at specific
      locations in the heart. This technique enables measurement with high spatial
      resolution. By its nature as a sampling system, however, PWD can not accurately
      measure Doppler shift frequency exceeding the Nyquist limit (PRF/2). In CWD,
      ultrasound pulses are continuously emitted and received by two separate
      transducers. Precise localization of a sampling volume is impossible in this
      technique, but CWD can determine higher flow velocity without ambiguity than that
      detected by PWD. CWD is useful to evaluate high-velocity blood flows such as
      those seen with valvular diseases or shunt lesions. CDI displays two-dimensional
      patterns of blood flow in colors, superimposed on the two-dimensional images of
      the heart structures. Thus, the velocity, direction and location of blood flows
      can be visualized in real-time. This technique facilitates detection of abnormal
      blood flows in the heart and major blood vessels, and it is also utilized to
      evaluate the severity of valvular regurgitation.

PMID- 8741477
TI  - [Anesthetic management of a patient with renal cell carcinoma extending into the
      right atrium].
AB  - A 60-year-old man with renal cell carcinoma extending through inferior vena cava
      into the right atrium was scheduled for the removal of the right kidney under
      general anesthesia and the cardiopulmonary bypass technique. In order to obtain a
      clear operative field and to minimize the risk for pulmonary embolism of
      necrotizing tumor, total circulatory arrest under profound hypothermia (20
      degrees C) was performed. Anesthesia was maintained with high doses of fentanyl
      (62 micrograms.kg-1), midazolam and supplemented with enflurane. We attempted to
      prevent circulatory collapse due to acute pulmonary embolism by tumor fragments
      during operation. The body temperature of the patient was decreased down to 20
      degrees C for protecting central nervous system with the minimal damage. No
      complications occurred during anesthesia and the post-operative period. For the
      safe anesthetic management of the patient such as our case, adequate monitoring
      of circulation and protection of central nervous system are essential.

PMID- 8741478
TI  - [Anesthesia for a patient with severe aplastic anemia].
AB  - A 48-year-old female with severe aplastic anemia was scheduled for transurethral
      lithotomy because of pyelonephritis and urethral stone. Laboratory studies showed
      anemia (168 x 10(4).mm-3), leukopenia (2300.mm-3) and thrombocytopenia (5000.mm
      3). Bleeding time exceeded 30 min, but the transfusion of fresh platelet
      concentrate was not effective for bleeding tendency. Anesthesia was induced with
      midazolam 0.5 mg and fentanyl 100 micrograms, and maintained with N2O-O2
      sevoflurane through a mask. The operation, which lasted for 40 min, was
      uneventful without marked hemodynamic changes, bucking or massive bleeding.
      Although 100 units of fresh platelet and 13 units of leucocyte poor red cells
      were infused during hospitalization, macrohematuria continued for about 3 weeks
      after this operation.

PMID- 8741479
TI  - [Perioperative management for partial resection of a lymphangioma of the tongue].
AB  - Twelve month old boy had been suffering from a neck lymphangioma. Partial
      resection was carried out in his newborn period at another hospital, and he was
      obliged to be tracheostomied because of severe airway obstruction due to
      postoperative edema. He was scheduled for partial glossectomy since his tongue
      had increased in mass, which could easily be injured by teeth, and he had
      difficulties in swallowing recently. His airway was not obstructive even during
      sleep and preoperative MRI showed adequate space around the larynx. We induced
      anesthesia by a mask and he was subseqently intubated with a fiberscope via his
      nose because his huge and less mobile tongue could not allow the insertion of a
      laryngoscope and this might cause bleeding. We did not extubate the endotracheal
      tube for fear of airway obstruction attributable to postoperative edema. Marked
      edema around the neck persisted longer than we expected. We tried to evaluate the
      degree of diminution of edema with MRI twice to decide when extubation could be
      attempted. However, examination with MRI could not give us useful informations.
      Consequently we evaluated the timing of extubation by examining whether he could
      close his mouth or not, whether his tongue could move freely and the degree of
      edema. We realized lymphangioma caused marked and extensive edema after the
      operation and we should keep in mind that lymphangioma of the tongue might cause
      various anesthetic problems especially on airways.

PMID- 8741480
TI  - [Use of Warm Touch for intraoperative hypothermia].
AB  - A 63-year old man was scheduled for nephrectomy and cholecystectomy. Anesthesia
      was maintained by oxygen-nitrous oxide-isoflurane (0.5 approximately 1%) and
      epidural anesthesia. Operation was performed with the patient on left decubitus
      position. At this time, rectal temperature as his core temperature was 35.8
      degrees C. Active warming with electrical warming mattress was started and the
      room temperature was maintained at 25 degrees C during the operation. Thirty
      minutes after the abdominal incision, rectal temperature decreased to 34.5
      degrees C. Active warming was started with forced-air warming system (Warm Touch,
      Mallinckrodt Medical Co.) on his upper body. Ten minutes after warming, his body
      temperatures were restored gradually. Three hours after using Warm Touch, rectal
      temperature recovered to 36.1 degrees C. The intraoperative course was
      uneventful. At the end of the operation, the patient showed no shivering and
      general condition was good. In this case, Warm Touch is useful to restore body
      temperature against intraoperative hypothermia during abdominal surgery.

PMID- 8741481
TI  - [Sudden syncope during spinal block under sitting position: a report of three
      cases].
AB  - We reported 3 cases of sudden syncope during saddle block under sitting position.
      Patients were healthy and had no history of fainting. Syncope occurred following
      hypotension and bradycardia during difficult lumbar dural punctures under sitting
      position. Patients were treated successfully by changing position to supine,
      elevating both legs and giving vasopressors. Neurocardiac syncope due to the
      activation of afferent cardiac C-fiber has been suggested as a possible
      explanation in sudden syncope, which follows head-up position or emotional
      change. The first sign of syncope was hypotension and bradycardia due to cardiac
      C-fiber reflex. How to prevent this NCS under saddle block are as follows; 1.
      vigorous search for history of syncope, 2. pay attention to the patients during
      spinal tap, 3. skillful technique in spinal tap, and 4. proper premedication
      including anticholinergic agents. Treatments include 1. changing position to
      supine, 2. elevation of both legs to increase ventricular end-diastolic pressure,
      and 3. use of vasopressors including phenylephrine.

PMID- 8741482
TI  - [Cesarean section under spinal anesthesia for a patient with chronic renal
      failure].
AB  - A 37-year-old primipara was scheduled for cesarean section under spinal
      anesthesia in the 38th gestational week because of cephalo-pelvic disproportion.
      She had suffered from chronic renal failure since 27 years of age, and had been
      undergoing hemodialysis three times per week. The frequency of hemodialysis was
      increased to 4-6 times per week during pregnancy to maintain blood urea nitrogen
      and serum creatinine concentration below 60 mg.dl-1 and 6.0 mg.dl-1,
      respectively. Since she had no bleeding tendency, spinal anesthesia with 8 mg of
      tetracaine was successfully performed after hemodialysis eliminating only solute
      but not water in the morning of surgery and after infusion of 500 ml of acetated
      Ringer solution. Blood pressure and heart rate were stable during surgery.
      Monitoring of central venous pressure was useful for fluid management. A baby
      weighing 2,575 g with an Apgar Score of 8 at one minute and 9 at five minutes was
      delivered five minutes after the beginning the surgery. The mother recovered
      uneventfully and returned to regular hemodialysis on the first postoperative day.
      These findings suggest that with careful fluid management, spinal anesthesia can
      be safely performed for cesarean section, for patients undergoing hemodialysis.

PMID- 8741483
TI  - [Myocardial ischemia induced by air bubbles].
AB  - Intraoperative transesophagial echocardiography (TEE) was performed in a 27-year
      old man who underwent direct suture for atrial septal defect (ASD) under general
      anesthesia. Myocardial ischemia occurred about five minutes after weaning from
      cardiopulmonary bypass, and at that time TEE showed that anteroseptal wall,
      lateral septal wall and lateral wall are severely hypokinetic and another wall is
      diffusely hypokinetic in the left ventricle after detecting air bubbles in the
      left ventricle by TEE. The changes in TEE preceded the ST elevation in the ECG.
      Bolus infusion of isosorbide dinitrate and continuous infusion of nitroglycerin
      showed no effects on these changes. Ten minutes after the onset of myocardial
      ischemia, these changes were alleviated. TEE enabled us to detect air bubbles and
      evaluates myocardial ischemia before the appearance of ST changes in ECG.

PMID- 8741484
TI  - [Helical CT guided lumar sympathetic ganglion block].
AB  - Helical CT scan was used as a guide for lumbar sympathetic ganglion block. By
      examining anatomical location of the block site with the sequential fluoroscope
      pictures of helical CT scan, we succeeded in the block of sympathetic ganglion
      easily. It is possible by the use of sequential CT picture to reduce the risk of
      puncturing essential organ such as the kidney, descending aorta, inferior vena
      cava and so on. Moreover, we can expect that application of helical CT scan will
      raise the success rate of block and will decrease the time necessary for the
      performance of block.

PMID- 8741485
TI  - [A comparative study of three types of tympanic membrane temperature monitoring].
AB  - We compared three types of tympanic membrane thermometer, Bi-Temp TM-200D (RSP),
      Mona-Therm (MT), and Quick Thermo (QT). RSP uses a thermister method, MT a thermo
      couple method, and QT detects an infrared energy. The tympanic membrane
      temperature measured with RSP correlated significantly with those measured with
      MT or QT. RSP showed temperatures 0.5 to 0.6 degree C lower than MT and 0.3
      degree C lower than QT. At the initial phase of monitoring the temperature, RSP
      showed a gradual increase to a stable temperature. However, MT indicated a
      transient increase followed by a decrease to a stable temperature. Both reached
      to stable temperatures in 100 to 120 seconds. These characteristics of
      thermometers should be considered when we compare the tympanic membrane
      temperature measured with various thermometers.

PMID- 8741486
TI  - [Comparison of a new double-lumen endobronchial tube by Portex with Broncho
      Cath].
AB  - We compared the clinical usefulness of two double-lumen endobronchial tubes, one
      furnished by Concord Portex and the other Broncho-Cath by Mallinckrodt. Only left
      sided 37 french size tubes were used. The difficulty of intubation, the opening
      state of the bilateral lumen in a bronchus, the displacement of the tube in
      changing a position, and easiness of passing the fiberbronchoscope or suction
      tube were compared in using the two double lumen endobronchial tubes. All
      parameters were slightly better in the Portex tube than in the Broncho-Cath, but
      the differences were not significant. It is concluded that the Portex tube is as
      useful as the Broncho-Cath or it may be superior to the Broncho-Cath.

PMID- 8741487
TI  - [Usefulness of "Valve Checker" for inspecting anesthesia machine and respiratory
      circuit].
AB  - We introduce a method for inspecting the function of the respiratory circuit of
      an anesthesia machine using "Valve Checker" devised by a manufacturer. With this
      method, the function of an inspiratory valve can be confirmed by the pressure not
      being removed when pressure is applied by connecting the "Valve Checker" directly
      with the inspiratory opening. Additionally, the function of an expiratory valve
      can be confirmed by the pressure being removed and also by the deflated bag being
      inflated when pressure is applied by connecting the "Valve Checker" directly with
      an expiratory opening. This is a method whereby a delicate cushioning of pressure
      by a hose is excluded and the function of the inspiratory valve and expiratory
      valve can be inspected independently and easily.

PMID- 8741488
TI  - [Expired gas analysis--focused on VO2 max and anaerobic threshold].
AB  - Recently, expired gas analysis(EGA) during exercise testing is broadly performed.
      It has been recognized that anaerobic threshold(AT) and maximal oxygen uptake(VO2
      max) may be useful in identifying one's exercise tolerance. AT especially has a
      good correlation with endurance capacity. In the field of sports medicine, the
      purposes of EGA are: 1) evaluation of endurance exercise capacity. 2) decision of
      intensity and frequency for exercise training, and 3) prevention of overtraining
      syndrome. In the clinical fields, EGA is frequently performed with cardiovascular
      patients, for example, myocardial infarction(MI), and congestive heart
      failure(CHF). The purposes are: 1) decision of intensity for exercise therapy
      with the patients of old MI. 2) evaluation of exercise capacity with the
      patients' of CHF. 3) index of exercise therapy for hypertension, hyperlipidemia,
      and diabetes, and 4) evaluation of drug effects including vasodilators and
      cardiotonics.

PMID- 8741489
TI  - [Sports and electrocardiograms].
AB  - The electrocardiographic examination in sports is performed as a screening
      procedure for athletes with complaints of cardiac symptoms. The resting 12-lead
      electrocardiogram(ECG) is the first step and the 2nd step is an exercise ECG and
      an ambulatory ECG. To evaluate the ECG findings of athletes, it is important to
      discriminate between an athletic heart and a diseased heart, because an athletic
      heart is often associated with ECG findings which are difficult to discriminate
      from those of a diseased heart. The bradycardic arrhythmia, high voltage and ST-T
      changes are characteristic of the athletic heart syndrome, which are difficult to
      differentiate from sick sinus syndrome and cardiomyopathy. In the general
      population, ECG, especially exercise ECG is also performed as a screening
      procedure for coronary heart disease before participating in sports. In these
      cases, exercise ECG yield many false positive results. It is important to
      determine the indications of the test. Another screening procedure of ECG is a
      diving reflex test. When we immerse our face in water, bradycardia occurs. This
      test might be used as a screening test for those beginning a water sport.

PMID- 8741490
TI  - [Sport-anemia: studies on hematological status in high school boy athletes].
AB  - High prevalence of anemia and iron deficiency state are found among athletes. To
      determine the influence of sports activities on the hematological state, we have
      performed hematological tests and examined the iron metabolism, in addition to
      some serum enzyme activities and some characters of red blood cells before and
      after exercise in high school boy athletes. The red blood cell count, hemoglobin
      level, and hematocrit value were significantly lower than those in the non
      athletes boy students. The serum ferritin level in the athletes was significantly
      lower than that in the control group and healthy adults. Iron deficiency anemia
      was found in 12% of the athletes. The serum haptoglobin level in the athletes was
      significantly lower than that in the control group and the level before exercise,
      suggesting intravascular hemolysis, but the serum hemopexin level showed no
      difference before and after exercise, suggesting that the hemolysis was not so
      severe. The serum CPK and myoglobin levels showed a significant increase after
      exercise, but those levels were quite lower than that of muscle diseases. These
      findings suggest that daily exercise is closely associated with the increased
      risk of iron deficiency state, particularly in the high school boy athletes. The
      mechanism of hemolysis in athletes may partly depend on the increased fragility
      of iron deficiency red blood cells on mechanical strength.

PMID- 8741492
TI  - [Sports and measurement of components in urine--responses of renal blood flow,
      electrolytes and hormones and of excretion of proteins into urine to exercise].
AB  - Renal blood flow decreased depending on the increase in exercise intensity. The
      kidneys may have roles to conserve the electrolytes and body fluid, and
      maintenance of acid-base balance during and after severe exercise. Increases in
      plasma hormones involved in the regulation of electrolyte-water balance, and
      decreases in urine flow, Na, Cl and K excretions into urine were observed
      following moderate exercise under a warm environment. Inhibition of electrolytes
      and water excretion into urine following exercise in water was less than that
      following exercise on land. Exercise in water is good for patients with
      hypertension, obesity and a mild renal disease who have tendency to conserve
      sodium and/or water. Increase in urinary albumin excretion, glomerular-type
      proteinuria was observed after moderate exercise (50 approximately 75%HRmax) in
      the obese individuals who had higher levels of hematocrit, serum concentrations
      of triglyceride, total cholesterol, LDL-cho, apoprotein B, CIII, and fasting
      insulin. The findings suggest that moderate exercise causes a latent abnormality
      of renal glomerular basement membrane in the obese individuals who had an early
      disturbance of glucose-fatty metabolism.

PMID- 8741491
TI  - [Urinary proteins (focusing on alkaline phosphatases)].
AB  - In order to gain a fuller understanding of sports-related stress markers, we
      studied urinary alkaline phosphatase (ALP) levels and isozyme patterns before and
      after strenuous exercise. ALP activity-peaks were seen 5 approximately 15 minutes
      or 1 hour after running. While levels of ALP of higher molecular mass were
      observed to increase slightly, following intense exercise, neither the intensity
      nor the duration of the exercise appeared to have an overly significant effect on
      them. After buthanol extraction, a distinct band of ALP activity was observed in
      the polyacrylamide gel, having the same degree of mobility as those of the renal
      cortex and medulla. A portion of post-exercise urinary ALP was considered to have
      originated from the kidney. As ALP is now understood to be one of the markers of
      bone metabolism, urinary ALP will most certainly come under ever more intense
      scrutiny, as regards its connection to sports-related stress and osteoporosis.

PMID- 8741493
TI  - [Determination of PIVKA-II levels in patients with small hepatocellular carcinoma
      -comparison of new sensitive methods].
AB  - Current EIA for PIVKA-II is not sensitive enough to detect small Hepatocellular
      Carcinoma (HCC). In an attempt to increase the diagnostic threshold, the current
      EIA was modified in two different ways: 1) immunoreaction of PIVKA-II in the
      sample with its monoclonal antibody was carried out overnight at 5 degrees C
      instead of for two hours at room temperature (the overnight method), 2) Avidin
      Biotin technique was used for the second reaction(the ABC method);and their
      diagnostic values were determined as compared with the current EIA(2hr method) in
      a total of 138 patients including 36 patients with HCC. In 27 patients with HCC(<
      3 cm in diameter), the rates of abnormal values obtained by the 2hr-, the
      overnight- and the ABC method were 14.8, 25.9 and 29.6% respectively. False
      positive rates of these three methods in 69 patients with liver cirrhosis were
      1.4, 8.6 and 22.9% respectively. Thus, these two modifications improved the
      sensitivity of the current EIA and the overnight method appears to be superior to
      the ABC method in terms of specificity and simplicity. This conclusion was
      confirmed by ROC analysis.

PMID- 8741494
TI  - [Optimal fixation for the detection of anti-neuronal antibody by
      immunohistochemistry in the paraneoplastic syndrome].
AB  - Paraneoplastic syndrome(PS) associated anti-neuronal autoantibodies are
      characterized by their antigen molecular weight determined by Western blot and
      immunostaining pattern recognized through immunohistochemistry. We investigated
      immunohistochemical fixatives for their sensitivity in the detection of anti
      neuronal nuclear antibody(Hu). Serum used for this study was taken from a patient
      with anti-Hu antibody seropositivity, which was ascertained by recombinant Hu
      protein. Western blot analysis produced 37kDa band. We examined six fixative
      conditions: immersion fixed with acetone, Bouin's solution, Sakura rapid
      fixative("Ufix'), and perfusion fixed with 2%, 4%, 8% paraformaldehyde (PFA) on
      the basis of each immunoreactivity in a rat cerebellum, brain stem and liver. The
      optimal fixation for detecting anti-Hu antibody was perfusion fixed with 2% PFA,
      that reacted conspicuously with nucleus but not nucleolus of neurons. The
      perfusion method proved superior to immersion in immunostaining intensity. With
      immersion fixation, specific immunostaining pattern lessened and differentiation
      from cytoplasm decreased. With various concentrations of PFA, immuno-reactivity
      with nucleus at 2% PFA was similar to 4%, although serum optimal dilution at 2%
      was slightly greater than 4%. The variety of staining patterns of anti-Hu
      antibody is closely related to the vulnerability of neuronal antigens to the
      fixatives. The detection of anti-neuronal antibodies is important for early
      diagnosis and treatment of occult tumors. The immunostaining method is a useful
      and sensitive way to research these antibodies. Therefore, it is essential to
      consider the selection of fixation and the preservation of the antigenicity in
      evaluating immunohistochemical hallmarks.

PMID- 8741495
TI  - [Expression of pS2-protein in breast cancer].
AB  - We studied the relationship between pS2-protein and estrogen receptor in breast
      cancer tissue immunohistochemically using paraffin-embedded sections obtained
      from 96 primary breast cancer tissues in which the estrogen receptor had been
      examined by ERICA using frozen section. ER-negative breast cancer specimens were
      negative for pS2 in 85% of the cases, and ER-positive breast cancers were
      positive for pS2 in 66% of the cases, the entire concurrence rate between pS2 and
      ER being 73%. Although the agreement was statistically significant, it seemed to
      be unreasonable that pS2 could replace ERICA in the routine detection of ER.
      However, the cases with pS2 stained (+2) or (+3) might be ER positive. pS2 showed
      a positive correlation to ER and PgR, and negative correlation to p53. This
      suggested that pS2 is a prognostic factor in breast cancers. Our findings
      suggested that pS2 also is a new marker of hormonal therapy for breast cancer.

PMID- 8741496
TI  - [Evaluation of differential media in Helicobacter pylori culture].
AB  - Culture is one of the important methods for detecting Helicobacter pylori(Hp).
      Culture method is generally lower sensitive in comparison with other Hp detection
      methods. However, culture is necessary for determination of MIC and analysis of
      bacteriological characteristics. Several culture media are now commercially
      available for Hp. In this study, we compared commercial media with our original
      medium. Original medium for Hp culture was most sensitive and showed no false
      positive results compared with other commercial media.

PMID- 8741497
TI  - [Variations of serum amyloid A protein and interleukin-6 in patients with low
      concentration of serum C-reactive protein].
AB  - Both C-reactive protein (CRP) and Serum amyloid A protein(SAA) are determined as
      an indicator of inflammation and tissue damage. But serum CRP in the range less
      than 10 micrograms/dl was not correlated with SAA. We determined CRP, SAA and
      interleukin-6(IL-6) in sera of patients who had received corticosteroid therapy.
      CRP decreased extremely after administration of more than 50 mg/day
      corticosteroid. However, SAA and IL-6 levels changed independently from CRP
      levels. In the patients under long-term corticosteroid therapy, CRP decreased
      rapidly to the level below the reference range and remained low, while SAA
      decreased but to the level in the reference range, and IL-6 levels was unchanged.
      When they were complicated with infectious disease during the corticosteroid
      therapy, CRP increased to or above the reference level but not so markedly,
      however, SAA increased markedly and exceeded the upper reference range three or
      four days earlier than the day of CRP increase. It is suggested that serial SAA
      monitoring will be reliable for the early diagnosis of infection if the patients
      is taking corticosteroid therapy.

PMID- 8741498
TI  - [Analysis of mutations and heteroplasmy at mitochondrial DNA 11778 using non-RI
      single strand conformation polymorphisms in Leber's hereditary optic neuropathy].
AB  - Leber's hereditary optic neuropathy(LHON) is a maternally inherited mitochondrial
      disease of an acute or subacute bilateral loss of central vision. G to A
      substitutions at nucleotide position 11778 in mitochondrial DNA(mt DNA) have been
      identified in approximately 40% to 90% of patients. In this study, regions
      containing mt DNA 11778 mutations were analyzed by polymerase chain
      reaction(PCR), non-RI single strand conformation polymorphisms(SSCP) and direct
      sequencing. In 26 visually affected patients, mt DNA 11778 mutations were
      detected in 9 patients (36.4%). In one pedigree of a LHON patient(L-6), four
      unaffected family members had heteroplasmy of the 11778 mutation using non-RI
      SSCP. Ratios of the heteroplasmy between wild type and mutant mt DNAs can be
      detected in non-RI SSCP and accurately quantified by video densitometric
      analyzer. Two types of novel polymorphisms, 11696 G to A and 11719 A to G, in the
      mt DNA region were also found in this non-RI SSCP analysis. Non-RI SSCP is an
      efficient and accurate method for diagnosis of mt DNA 11778 mutations and
      quantifying heteroplasmy in patients with LHON and pedigrees.

PMID- 8741499
TI  - [Improved method of staining RNA in platelets for the evaluation of platelet
      production in thrombocytopenic patients].
AB  - Measurement of RNA stained platelets was proven to be an easy and useful
      laboratory test to evaluate the state of platelet production in the bone marrow.
      As the normal value of RNA stained platelet with thiazole orange(TO) in the
      original method was low, the values of TO-stained platelets in the cases with
      platelet hypoproduction were within the normal range, but ideally, they should be
      below the normal range. We modified the original method 1) by using sodium
      citrate as the anticoagulant instead of EDTA, and 2) by keeping the TO-stained
      preparation at 4 degrees C until the fluorescence was measured. The normal value
      of TO-stained platelets was elevated to 22.5 +/- 3.3% (n = 40, M +/- 1SD) or 54
      +/- 10 x 10(9)/1. Twenty-seven out of 40 thrombocytopenic case with ITP showed an
      elevated percentage of TO-stained platelets, 11 cases showed a normal and only 2
      cases showed a percentage lower than normal. By contrast, 9 out of 12 cases with
      platelet hypoproduction showed a lower percentage of TO-stained platelets and no
      cases showed a value higher than normal. The sensitivity and specificity of this
      modified RNA staining method for distinguishing thrombocytopenic cases with
      platelet hyperdestruction from that with hypoproduction were 96% and 75%,
      respectively.

PMID- 8741500
TI  - [The production of high sensitive anti-myeloperoxidase monoclonal antibodies and
      their sensitivity and specificity].
AB  - We produced anti-myeloperoxidase(MPO) monoclonal antibodies(moAb) to detect MPO
      sensitivity in leukemic cells by visual light microscopy. We got seven kinds of
      moAbs which showed different properties to MPO. These antibodies reacted to MPO
      in immature and mature neutrophils, monocytes and HL-60(human myeloid leukemic
      cell line) by immunochemical detection using the avidin-biotin complex(ABC)
      staining method, but the amounts of immune complex products were significantly
      different at each moAb. MPO2, MPO4, MPO9 and MPO13 moAbs blocked MPO activities
      but MPO5 showed no such inhibition. Most of the moAbs reacted to 59kD MPO moAb
      using the western blotting method, while MPO4 and MPO5 reacted to both 81kD and
      89kD MPO precursors. This data suggests that these moAbs are useful to
      demonstrate a small amount of MPO in leukemic cells.

PMID- 8741501
TI  - [Transitions of each inhibitor in a patient with lupus anticoagulant and anti
      prothrombin antibody].
AB  - In a 2-year-old girl showing purpura on her legs after administration of
      antibiotics, marked prolongation of activated partial thromboplastin time(APTT)
      and prothrombin time was noted. Circulating anticoagulants were demonstrated by
      the failure to correct APTT on neutralization test. A lupus anticoagulant(LA),
      one of the circulating anticoagulants, was detected by rabbit brain phospholipid
      neutralization procedure and platelet neutralization procedure. On crossed
      immunoelectrophoresis, the abnormal prothrombin peaks with reduced
      electrophoretic mobilities were considered prothrombin/prothrombin-antibody
      complexes because pretreatment with anti-human IgG serum caused their
      disappearance. This prothrombin-antibody seemed to be another circulating
      anticoagulant. The anti-prothrombin-antibody reduced prothrombin activities in
      the circulating blood of the patient to 20 approximately 30% of normal and the
      condition persisted for two weeks resulting in the purpura which occurred during
      that period. After two months, APTT was restored to normal following the
      disappearance of LA.

PMID- 8741502
TI  - [A functional diagnostic method by measuring of distribution volume of 123I-IMP
      with SPECT].
AB  - To measure distribution volume of 123I-IMP with one-point sampling of arterial
      blood and 2 times SPECT scans using the Magic square method (Rate constant square
      method), we introduced a program on a SPECT computer system. In this program four
      functional images; distribution volume, CBF (K1), k2 and delayed/early ratio, and
      absolute values with S.D. are obtained on the computer. We have been using the
      program on daily SPECT studies. In this study we discussed the usefulness of the
      method. Redistribution phenomenon of 123I-IMP, which is not exactly enough
      investigated, can be transformed into a functional parameter, distribution
      volume. Since distribution volume represents an extent of retention of 123I-IMP
      in brain tissue, it can play an important role to evaluate functional activity in
      the brain and to diagnose cerebral diseases.

PMID- 8741503
TI  - [Evaluation of 123I-iomazenil SPECT in patients with ischemic cerebrovascular
      disease: comparative study with 123I-IMP SPECT].
AB  - Clinical evaluation of 123I-iomazenil, a new imaging agent for central-type
      benzodiazepine receptors with SPECT, was performed in patients with ischemic
      cerebrovascular disease. We investigated 15 patients with angiographically-proven
      severe occlusive lesions (occlusion or > 70% stenosis) in the unilateral carotid
      system. 123I-iomazenil SPECT images were compared with cerebral blood flow (CBF)
      images and the cerebral perfusion reserve, which were measured using the "split
      dose 123I-IMP SPECT method" before and after the intravenous injection of 1 g of
      acetazolamide. For the detection of ischemic lesions, CBF images were superior to
      123I-iomazenil images based on visual analysis. Regarding the count ratio of the
      affected MCA territory to the non-affected (L/N), 123I-IMP was lower than 123I
      iomazenil in most of the cases. In five patients showing "crossed cerebellar
      diaschisis" by 123I-IMP, asymmetry of the cerebellar accumulation was observed in
      only one patient with 123I-iomazenil, which was less prominent than with 123I
      IMP. There was no significant correlation between the L/N ratio with 123I
      iomazenil and the cerebral perfusion reserve in the affected MCA territory.
      However, in some cases showing a decreased L/N ratio (< 90%) with 123I-iomazenil,
      a decreased CBF with normal perfusion reserve and cerebral hemi-atrophy were
      observed with 123I-IMP and MRI, which suggested the influence of neuronal loss
      due to chronic ischemia. These results indicate that 123I-iomazenil SPECT, which
      provides new information regarding neuronal loss due to ischemic damage to the
      brain, is useful for the evaluation of ischemic cerebrovascular disease.

PMID- 8741504
TI  - [Evaluation of myocardial damage using 123I-BMIPP imaging in patients with
      vasospastic angina].
AB  - The purpose of this study is to determine whether left ventricular dysfunction
      following coronary artery spasm by 123I-BMIPP myocardial imaging. To reveal the
      clinical efficacy of 123I-BMIPP SPECT, 20 patients with vasospastic angina were
      studied using resting, 3-hour delayed image with 123I-BMIPP and exercise, 3-hour
      delayed image with 201Tl SPECT. 123I-BMIPP uptake was decreased compared to 201Tl
      (discordant) in 12 patients (60%) and in 49/100 myocardial segments (49%). The
      extent and severity score in resting image with 123I-BMIPP were significantly
      larger than that in delayed image with 201Tl (p < 0.01). In 123I-BMIPP SPECT, the
      severity score in the latest ischemia were significantly larger than that in
      others. The incidence of a complete agreement of decreased 123I-BMIPP uptake and
      coronary artery spasm was significantly higher (75%) than that in 201Tl (28%, p <
      0.01). Furthermore, compared to 201Tl uptake, decreased 123I-BMIPP uptake much
      more corresponded to reduced wall motion in 9 of patients with mismatching. The
      severity of regional wall motion abnormality was significantly correlated with
      severity score of 123I-BMIPP. Late redistribution in delayed image with 123I
      BMIPP was seen in 6 patients. The regional washout rate and the severity of
      regional wall motion abnormality in 6 patients was significantly lower than that
      in others (p < 0.05). Thus, metabolic abnormality assessed by 123I-BMIPP is well
      associated with left ventricular asynergy and spastic region in patients with
      vasospastic angina. In conclusion, 123I-BMIPP SPECT may sensitively delineate the
      impaired myocardium following coronary artery spasm, and it is very useful in
      diagnosing and estimating the severity of vasospastic angina.

PMID- 8741505
TI  - [The regional wall motion and the myocardial fatty acid metabolism at hibernating
      myocardium].
AB  - To evaluate the regional wall motion and the myocardial fatty acid metabolism at
      hibernating myocardium after revascularization (PTCA or CABG), we performed dual
      SPECT with 201Tl and 123I-beta-methyliodophenyl-pentadecanoic acid (BMIPP), and
      left ventriculography (LVG) in 34 patients with coronary artery disease before
      and 3 to 4 months after revascularization. In the SPECT, regional tracer uptake
      was estimated qualitatively (visual) and quantitatively (% uptake). Regional wall
      motion was estimated qualitatively (visual) and quantitatively (shortening
      fraction). At the 78 hibernating areas, the improvement of regional wall motion
      was more significantly (p < 0.05) correlated with that of regional tracer uptake
      of 123I-BMIPP (r = 0.63) than 201Tl (r = 0.39), and also correlated with the
      improvement of the difference between 201Tl and 123I-BMIPP regional uptake (r =
      0.36). These results suggest that the improvement of wall motion at hibernating
      myocardium is more significantly correlated with the improvement of 123I-BMIPP
      than 201Tl uptake after revascularization.

PMID- 8741506
TI  - [Regional left ventricular contraction kinetics in patients with hypertrophic
      cardiomyopathy: investigation by ECG-gated myocardial SPECT with 99mTc-MIBI].
AB  - To investigate the regional left ventricular (LV) contraction kinetics in
      patients with hypertrophic cardiomyopathy (HCM), we performed ECG gated
      myocardial tomography (gated-SPECT) with 99mTc methoxy-2-isobutyl isonitrile
      (MIBI) at rest in 11 patients with HCM and 13 normal subjects. In order to
      evaluate regional LV contraction kinetics, multi-plane long axial tomograms were
      constructed and LV was divided into 17 segments. From the time activity curve of
      myocardial count, percent change during systole (%CC) was calculated in each
      segment. Normal range of %CC in each segment was derived from normal files.
      Systolic asynchrony in each patient was expressed as SD (standard deviation) of R
      wave to peak count (R-PC) intervals of 17 segments. Decreased %CC was observed in
      87 of 187 segments (47%) in HCM (8 +/- 5 segments/patient, range; 2-14
      segments/patient). SD in patients with HCM was significantly greater than that in
      normal subjects (5.9 +/- 1.3 vs. 3.5 +/- 0.6, p < 0.01). The extent of decreased
      %CC in patients with HCM correlated well with global 123I-BMIPP (BMIPP) uptake
      and the extent of regional abnormality of BMIPP (Defect Score) (r = -0.79, r =
      0.88 each, p < 0.01). On the other hand, SD correlated well with left ventricular
      (LV) filling rate during early diastole (r = -0.66, p < 0.01). Patients with HCM
      were divided into 2 groups whether LV ejection fraction (EF) increased (Group 1)
      or decreased (Group 2) by exercise stress. SD in Group 2 was significantly
      greater than that in Group 1. In segments with decreased %CC, the distribution of
      R-PC interval was different with that in segments with normal %CC. These results
      suggested that indexes which were derived from gated-SPECT with MIBI could bring
      several informations which were important to assess the pathologic condition of
      HCM.

PMID- 8741507
TI  - [201Tl SPECT for suspected lung cancer in a case of a systemic arterial supply to
      the lung without sequestration].
AB  - 201Tl SPECT showed negative result for the presence of a malignant lesion in a 54
      year-old male suspected with primary lung cancer on plain x-ray CT. Thin-section
      contrast x-ray CT and aortography revealed anomalous left lower pulmonary artery
      arising from the aorta which mimicked a pulmonary mass lesion in the initial
      study. 201Tl SPECT gave us a clue to the correct diagnosis.

PMID- 8741508
TI  - [ECG-gated myocardial SPECT with 99mTc-MIBI in patients with right ventricular
      infarction].
AB  - Although 99mTc-pyrophosphate (PYP) myocardial scintigraphy has so far been widely
      used for the diagnosis of right ventricular infarction, PYP accumulation
      disappears within one week or so. To evaluate the myocardial condition of the
      right ventricle alternatively, myocardial SPECT with 99mTc-MIBI was performed in
      16 patients with acute inferior left ventricular infarction, and ECG-gated
      myocardial SPECT data acquisition was accompanied in 14 of 16 patients. Right
      ventricular perfusion defect was observed in 4 of 16 patients (RVI (+) group),
      and the remains were negative (RVI (-) group). Then, right ventricular count
      increase rate (RV %WT) of MIBI from end-diastole to end-systole was calculated
      using an automated method which was developed for quantification of wall
      thickening in our laboratory. The RV %WT was conceived to be an objective index
      representing right ventricular contractility. RVI (+) group (n = 3) as compared
      with RVI (-) group (n = 11) had significant lower RV %WT (26.7 +/- 3.2 vs. 49.6
      +/- 14.2; p < 0.01). In conclusion, ECG-gated myocardial SPECT with MIBI was
      considered to be useful for assessment of myocardial perfusion and contractility
      of right ventricle.

PMID- 8741509
TI  - [Development of a front shield for a 3D positron emission tomograph].
AB  - Accidental coincidence rate and scatter coincidence rate of 3-dimensional (3D)
      acquisition of positron emission tomograph (PET) are higher than 2-dimensional
      (2D) acquisition and count loss becomes higher because slice shield collimator is
      not used in 3D acquisition. If one could decrease the gamma ray from outside of
      the axial field of view (FOV), it may be possible to improve image quality of 3D
      acquisition. Thus, using a Shimadzu SET-2300W (Headtome V) PET camera, we
      developed and tested a front shield for brain study to shut off gamma ray from
      the outside of the axial FOV. Using the front shield, gamma ray from outside of
      the FOV and the accidental coincidence rate could be decreased. The count loss in
      high count rate was also decreased. With these effect, the image quality of the
      clinical studies in 3D acquisition could be increased.

PMID- 8741510
TI  - [Validation study in quantitative measurement of regional cerebral blood flow
      using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) and SPECT].
AB  - We validated following five methods to quantitate regional cerebral blood flow
      (rCBF) using 123I-IMP and SPECT; 1) microsphere method, which is based on a
      microsphere model using the SPECT image at five minutes after 123I-IMP injection
      with continuous withdrawal of arterial blood, 2) microsphere+ one-point sampling
      method, which is the same as the microsphere method except for using one-point
      sampling instead of continuous withdrawal, 3) conventional microsphere + one
      point sampling method, which is the same as the microsphere + one-point sampling
      method except for using a later SPECT image corrected with the ratio of
      alteration of measured entire brain activity, 4) Table look-up method, which is
      based on a two-compartment model (influx; K1 and outflux; k2) using one arterial
      blood sample taken at 10 min and two SPECT images at 30 min and 180 min post
      injection, and 5) functional IMP SPECT, which is based on the two-compartment
      model using one arterial blood sample taken at 5 min and two SPECT images at 30
      min and 60 min post-injection. Those methods were applied to six patients with
      cerebral infarction and degenerative diseases, and rCBF results were compared
      with those estimated by non-linear least squares fitting (NLLSF) analysis based
      on the two-compartment model. The rCBF values obtained by the microsphere method
      was best correlated with those by NLLSF analysis (r = 0.940), followed by the
      microsphere+one-point sampling method (r = 0.885) and the functional IMP SPECT (r
      = 0.882). The table look-up method underestimated rCBF especially at the high
      flow level, however showed good correlation (r = 0.859). The conventional
      microsphere + one-point sampling method overestimated rCBF, however showed good
      correlation (r = 0.849). Distribution volume (Vd = K1/k2) was also estimated by
      both the table look-up method and the functional IMP SPECT. While values of Vd by
      the functional IMP SPECT were significantly correlated with those by NLLSF
      analysis (r = 0.785), the table look-up method overestimated Vd (43.4 +/- 6.6
      ml/g) and showed not good correlation (r = 0.287).

PMID- 8741511
TI  - [A basic and clinical evaluation of a new immunoradiometric assay kit for human
      serum tissue polypeptide antigen (TPA)].
AB  - A new immunoradiometric assay kit (IRMA) of human serum tissue polypeptide
      antigen (TPA) based on combination monoclonal antibodies was evaluated. Using a
      new TPA-IRMA, the procedure of TPA measurement was faster and the range of
      measurement was more wide than a conventional TPA-IRMA. 89% (76/85 cases) of
      patients with malignant tumor and 96.4% (27/28) of patients with metastatic
      malignant tumor were positively detected. This assay of new TPA-M kit is
      sensitive to the level of serum TPA which is corresponding to a therapy. It is
      concluded that a new TPA-IRMA is very useful in monitoring and assessing
      malignant tumors.

PMID- 8741512
TI  - [Development of simple on-line [oxygen-15]water infuser].
AB  - A [15O]water production and infusion system was newly developed for blood flow
      study with positron emission tomography. The system utilizes a electrostatic
      cooling unit to liquify [15O]vapor in a coiled plastic tube. Labeled [15O]water
      is collected into an infusion syringe by a wash of the trapping tube with saline.
      The system is simple and efficient; the recovery rate of [15O]water is over 90%
      at 10 degrees C of cooling temperature.

PMID- 8741513
TI  - [Evaluation of the usefulness of 111In-DTPA-IgG scintigraphy for the detection of
      focal inflammatory lesions].
AB  - We evaluated the usefulness of 111In-DTPA-IgG scintigraphy for the detection of
      focal inflammatory lesions. We examined 9 patients with focal inflammatory
      lesions that had been diagnosed based on the findings of various types of
      laboratory data and other imaging modalities. Scanning was performed at 6, 24, 36
      and 48 hours after the administration of 80 MBq of 111In-DTPA-IgG. The
      sensitivity was 78%. A good diagnostic ability was observed by the scintigraphy
      findings at 24 hours. In conclusion, 111In-DTPA-IgG scintigraphy at 24 hours is
      thus considered to be useful for detecting focal inflammatory lesions.

PMID- 8741514
TI  - [The seventeenth report on Survey of the Adverse Reaction to Radiopharmaceuticals
      (the 20th survey in 1994). Subcommittee of Safety Issue for the
      Radiopharmaceuticals Medical and Pharmaceutical Committee. Japan Radioisotope
      Association].

PMID- 8741515
TI  - [Advanced dental technology and its clinical application in 21 century].

PMID- 8741516
TI  - [Electrical tooth stimulation and somatosensory evoked potential].

PMID- 8741517
TI  - [Characterization of rat periodontal ligament cells in culture].
AB  - It has been reported that periodontal ligament cells (PDLC) show osteoblastic
      phenotypes in culture. In most previous studies, PDLC have been obtained from the
      tooth root surface, however, a new method in which PDLC are obtained from the
      coagulum after tooth extraction has been proposed recently. To compare PDLC from
      tooth surface with these from coagulum, PDLC from both sources were cultured and
      examined. PDLC from both sources responded to PTH or PGE2 increasing cAMP and
      showed high alkaline phosphatase (ALP) activity. Some PDLC cultures produced
      mineralized tissues and these mineralizing cultures showed high ALP activity with
      high gene expression level of type I collagen, bone sialoprotein, and osteopontin
      in comparison with non-mineralizing cultures. PDLC from both sources expressed
      various osteoblastic or cementoblastic phenotypes and seemed to contain
      heterogenous mesenchymal cell population with various differentiation potentials.
      However, the frequency of cellular transmigration, rate of mineralized tissue
      formation, increased level of cAMP that responded to PTH or PGE2, and osteopontin
      expression pattern were different between PDLC from both sources. These
      differences indicate that PDLC cultures from coagulum contain more immature cells
      than PDLC from tooth surface.

PMID- 8741518
TI  - [Modulation of evoked potentials following electrical tooth stimulation by pre
      auditory stimulus].
AB  - Modulation of evoked potentials following electrical tooth stimulation (Dental
      EPs) and visual analogue scale (VAS) were studied in 11 healthy adult volunteers
      to investigate the possibility of controlling reaction of pain sensation by using
      pre-auditory stimulus. They were recorded by these two paradigms. 1) Only
      electrical tooth stimulation delivered in random interval. 2) A preceding tone
      beep, to enable subjects to anticipate the coming tooth stimulus. Preceding time,
      inter stimulation intervals (ISI) were 0.5, 1.0, 3.0, 5.0, and 7.0sec. The
      results were as follows: 1) The Dental EPs were recorded in every volunteer, and
      the N2-P2 amplitude was the largest at vertex areas (Cz). 2) The P2 latency and
      N2-P2 amplitude were modulated by the preceding tone beep, reduced in ISI = 0.5
      and 1.0sec, and increased in ISI = 5.0 and 7.0sec., and a linear correlation was
      found between their variations. 3) There were no significant differences in the
      VAS score between each paradigm. These findings suggested that: 1) The late
      component of Dental EPs reflects not only the physiological process of the pain
      sensation but also psychological process of expectation and anxiety. 2) Pre
      auditory stimulus and time lag between pre-auditory stimulus and electrical tooth
      stimulation influence the psychological process and modulate the Dental EP
      result.

PMID- 8741519
TI  - [An in vitro oral mucosal model reconstructed from human normal gingival cells].
AB  - In order to develop in vitro models which are similar to native tissues, human
      oral mucosal models were reconstructed from gingival cells in three-dimensional
      cultures and the characteristics of the models were examined. Keratinocytes and
      fibroblasts from human normal gingival tissues were cultured in Keratinocyte
      Growth Medium (KGM) and in Dulbecco's Modified Eagle's Medium (DMEM) supplemented
      with 10% fetal bovine serum (FBS) respectively. The models were reconstructed by
      seeding keratinocytes on contracted collagen gels containing fibroblasts (CCG),
      which corresponded to the lamina propria, and co-culturing in Reconstruction
      Medium composed of one part of DMEM supplemented with 10% FBS and three parts of
      1.5mM CaCl2-added-KGM at the gas-liquid interface for 10 days. Stratified
      epithelial layers were formed on CCG, and terminal differentiation of the
      keratinocytes were recognized in the epithelial layers. Cell nuclei were still
      observed in the keratinized layers such as parakeratinized gingival tissues.
      Involucrin expression in the epithelial layers showed normal distribution by
      immunohistochemical detection. Transmission electron microscopic observation
      demonstrated that, in the epithelial layers, the formation of intercellular
      desmosomes and intermediate filaments in cytoplasms increased from the basal
      layer to the keratinized layers. These results suggest that oral mucosal models
      are well-differentiated and histologically similar to native tissues.

PMID- 8741520
TI  - [Peculiar cemental lesion of the jaws--its pathological entity and natural
      history].
AB  - Two hundred fifty-five solitary and 42 multiple cases of fibro-osseous lesions of
      the jaws, and 74 cases of sclerosing osteomyelitis were studied clinico
      pathologically, in order to discuss the entity of peculiar cemental lesion with
      sequester-like appearance, which occurs mainly in the mandibular molar area of
      over middle-aged females. Four allied lesions, including the sequester-like
      cemental lesion, were revealed. They were provisionally designated sequestrated
      cemental masses, cemental masses, focal cemento-osseous dysplasia, and periapical
      cemental masses respectively, because no entities that were consistent with them
      could be found in the classifications of World Health Organization (WHO). The
      above- mentioned peculiar cemental lesion was equivalent to sequestrated cemental
      masses, which consist of sclerotic cementum and/or osteocementum with
      inflammation. Cemental masses and periapical cemental masses were related to
      sequestrated cemental masses. Focal cemento- osseous dysplasia was considered to
      be a counterpart of lesion which had been recently reported by Summerlin et al.
      In consideration of similarity and continuity of the histological and clinical
      findings, the four allied lesions were thought to be arranged in a continuous
      spectrum of fibro-cemento-osseous dysplasia of the jaws, along with periapical
      cemental dysplasia and florid cemento-osseous dysplasia that are mentioned in the
      WHO classification.

PMID- 8741521
TI  - [Functional analysis of transforming growth factor-beta type II dominant negative
      receptor].
AB  - The transforming growth factor-beta (TGF-beta) is a multifunctional homodimeric
      protein with an apparent molecular weight of 25 KDa. TGF-beta transduces signals
      by forming heteromeric complexes of their type-I (T beta R-I) and type-II (T beta
      R-II) serin/threonine kinase receptors. TGF-beta binds first to T beta R-II
      receptor, and then the ligand in this complex is recognized by T beta R-I,
      resulting in formation of a heteromeric receptor complex composed of T beta R-I
      and T beta R-II. Once received, T beta R-I becomes phosphorylated in the GS
      domain by the associated constitutively active T beta R-II and transmits the
      downstream signal. It has been reported that formation of the heteromeric complex
      is indispensible at least in epithelial cells for growth inhibition and
      extracellular matrix production induced by TGF-beta. In this study, the
      functional role of T beta R-II for the TGF-beta-induced signals in osteoblastic
      cells was investigated by using a dominant negative type of T beta R-II mutant
      receptors (T beta RIIDNR). ROS 17/2.8 and MG 63 cells were found to express T
      beta R-I, T beta R-II, and T beta R-III, and their cell growth was inhibited by
      TGF-beta, whereas alkaline phosphatase activity was stimulated. Cells that were
      stably transfected with the T beta RIIDNR plasmid showed decreased response to
      TGF-beta during growth and alkaline phosphatase activity. These results indicate
      that the intracellular serine/threonine kinase domain of T beta R-II is essential
      for signal transduction of the TGF-beta-induced alkaline phosphatase activity as
      well as growth inhibition.

PMID- 8741522
TI  - [Age-related functional changes of cancellous and cortical bone:
      histomorphometric study of bone in senescent rats fed with a low calcium diet].
AB  - Age-related functional changes of bone is not well understood. The effect of
      aging on bone response to a low calcium feeding was studied using senescent rats.
      Male Wistar rats aged 23 to 28 months were fed either a low calcium diet (0.05%
      Ca, 0.35% P) or a normal calcium diet (0.5% Ca, 0.35% P) by using a pair feeding
      technique. They were sacrificed at intervals of 6, 9, and 20 days. Bone mineral
      density of the femur showed no changes in both cancellous and cortical bone in
      the low calcium group compared with the normal calcium group. The increment of
      osteoclast number was observed on day 6 in the cancellous bone of the tibia, but
      no significant changes were found during other periods. Mineralizing surface
      (MS/BS) and mineral appositional rate (MAR) were increased during the
      experimental period. On the other hand, cortical bone showed a transient increase
      of MS/BS on day 6, but other parameters revealed no changes during the
      experimental period. The magnitude of response was more evident in the cancellous
      bone than in the cortical bone. These results indicated that although
      responsiveness of remodeling activity to low calcium feeding is decreased in
      senescent rats, they are obvious in both the cancellous and cortical bone.

PMID- 8741523
TI  - [Condylar movement in patient with skeletal mandibular prognathism during maximum
      opening and closing movement before and after surgery].
AB  - Condylar movement of patients with mandibular prognathism who received sagittal
      splitting ramus osteotomy (SSRO) was investigated using computer aided diagnostic
      axiography (CADIAX). Linear and angular parameters were used to evaluate the
      maximum opening and closing paths of the condyle projected on the sagittal plane.
      The motion paths of six subjects with mandibular prognathism (MP group) were
      examined immediately before surgery and during the retention period. The results
      were compared with the recording from six normal subjects (control group). The
      results were as follows: (1) The average change in the maximum translating
      distance of the condyle in the retention period was 99.4 +/- 14.5% of the
      presurgical value on right side and 97.8 +/- 20.8% on the left side. The
      difference was not significant. (2) The shape of the opening translating curve of
      the MP group was flatter than that of the control group, however, no significant
      differences were found between the pre- and postsurgical curves of the MP group.
      (3) The coordination between the maximum opening and closing paths of the control
      group was fairly stable and smooth. However, although some improvement was
      observed, the paths of the MP group were unstable even after surgical treatment
      and large individual variations were observed.

PMID- 8741524
TI  - [Introduction of an improved face simulation system].

PMID- 8741525
TI  - [Three cases of tuberculous mediastinal lymphadenitis].
AB  - Mediastinal lymph node involvement is uncommon in intrathoracic tuberculosis. We
      report three cases of this disease, each of which had a different clinical
      course. Chest CT scans showed preferential involvement of right paratracheal
      nodes, central areas of relatively low density with peripheral rim enhancement
      after injection of contrast medium. Specimens obtained by mediastinoscopy and
      fiberoptic bronchoscopy revealed acid-fast bacilli in all cases. In view of its
      relative frequency, tuberculous mediastinal lymphadenitis in adults must be
      distinguished from other causes of mediastinal masses.

PMID- 8741526
TI  - [T-kinin-induced increase in airway vascular permeability and its modulation by
      angiotensin-converting enzyme].
AB  - We studied the effect of T-kinin on airway vascular permeability and its
      modulation by endogenous peptidases in anesthetized rats in vivo, Vascular
      permeability was assessed by photometric measurement of extravasated Evans blue
      dye after formamide extraction. Intravenous injection of T-kinin increased dye
      extravasation in the trachea and main bronchi in a dose-dependent manner. Plasma
      extravasation evoked by T-kinin was inhibited by Hoe 140, a B2 receptor but-not
      by des Arg9-Leu8-bradykinin, a B1 receptor antagonist. Treatment with captopril,
      an angiotensin-converting enzyme inhibitor, potentiated the T-kinin-induced
      plasma extravasation, whereas phosphoramidon, a neutral endopeptidase inhibitor,
      had no effect. These results suggest that T-kinin increases airway vascular
      permeability via stimulation of B2 receptors, and that this effect is modulated
      by endogenous angiotensin-converting enzyme.

PMID- 8741527
TI  - [Regulation of cyclooxygenase activity in airway epithelium by endogenous nitric
      oxide].
AB  - The role of nitric oxide (NO) in the activity of cyclooxygenase (COX) in cultured
      canine tracheal epithelium was studied. Tracheal epithelium spontaneously
      released prostaglandin E2 (PGE2), which is a product of COX. The release of PGE2
      was increased by bradykinin and was decreased by two NO synthase inhibitors: NG
      nitro-L-arginine methyl ester and NG-monomethyl-L-arginine. That decrease was
      reversed in the presence of L-arginine. Chrolpromadin, but not aminoguanidine,
      inhibited PGE2 production, which suggests that constitutive NO synthase is
      involved. Two stable NO donors, sodium nitroprusside and S-nitroso-N-acetyl DL
      penicillamine, also increased the production of PGE2. These effects were
      abolished by coincubation with hemoglobin, which binds and inactivates NO, but
      not by methylene blue, an inhibitor of soluble guanylate cyclase. NADPH
      diaphorase histochemistry of cultured tracheal cells revealed activity in the
      periphery of the cytoplasm. These results suggest that, in cultured canine
      tracheal epithelium, NO directly interacts with COX to regulate PGE2 production.

PMID- 8741528
TI  - [Use of the the ED046 kit to analyze serum KL-6 in patients with pneumonitis].
AB  - KL-6 is a mucinous glycoprotein expressed on Type 2 pneumonocytes, and serum
      levels of KL-6 are reported to be abnormally high in patients with interstitial
      pneumonia. A new assay kit for serum KL-6 (ED046) was used in the evaluation of
      patients with pneumonitis. To clarify whether KL-6 is a useful marker of
      pneumonitis activity, 649 subjects were studied, including 185 healthy controls,
      187 patients with 3 types of interstitial lung diseases, and 277 patients with 4
      types of non-interstitial lung diseases. The serum KL-6 level was significantly
      higher in the patients with pneumonitis (1285 +/- 1196 U/ml) than in the patients
      without pneumonitis (307 +/- 232 U/ml). The KL-6 level was also significantly
      higher in patients with clinically active pneumonitis (1708 +/- 1338 U/ml) than
      in those with inactive pneumonitis (820 +/- 796 U/ml) (p < 0.0001). Serum KL-6
      levels correlated significantly with serum c-reactive protein, lactic
      dehydrogenase, and PaO2 values. These results suggest that the ED046 assay is
      useful for measuring KL-6 as a marker of pneumonitis activity.

PMID- 8741529
TI  - [Clinical effects of four weeks of respiratory muscle stretch gymnastics in
      patients with chronic obstructive pulmonary disease].
AB  - We developed a program of respiratory muscle stretch gymnastic (RMSG), and
      measured lung function, exercise capacity, dyspnea, and quality of life before
      and after 4 weeks of training with this program. Thirteen patients with chronic
      obstructive pulmonary disease (mean FEVi, 1.24 liters) began the program. They
      participated in three sessions of RMSG each day. Twelve patients completed all 4
      weeks. RMSG significantly (p < 0.01) decreased functional residual capacity (from
      4.19 +/- 1.27 to 3.88 +/- 1.03 liters), total lung capacity (from 5.98 +/- 1.35
      to 5.66 +/- 1.20 liters), residual volume (from 3.29 +/- 1.16 to 2.89 +/- 0.89
      liters), and residual volume as a percent of total lung capacity (from 53.9 +/-
      11.2% to 50.6 +/- 9.74%). The distance walked in 6 min increased by an average of
      43 +/- 30 meters (+ 15%, p < 0.01). Dyspnea after a 6-minute walk (measured with
      a 150-mm visual analog scale) decreased significantly (from 65.1 +/- 40.8 to 36.1
      +/- 36.8, p < 0.05). Quality of life was measured with the Chronic Respiratory
      Disease Questionnaire of Guyatt, et al., and was found to have improved
      significantly. Respiratory muscle stretch gymnastics may be useful in pulmonary
      rehabilitation.

PMID- 8741530
TI  - [Characteristics and management of patients with lung cancer and idiopathic
      interstitial pneumonia].
AB  - Among 102 patients with idiopathic interstitial pneumonia (IIP), 22 with lung
      cancer who were treated from 1981 to 1994 were studied retrospectively. As
      controls, 248 patients with lung cancer only who were treated from 1991 to 1992
      were also studied. Lung cancer developed in 6 of 85 patients after IIP was
      diagnosed (7.1%). The time from the onset of IIP to the onset of lung cancer was
      7.7 years. In 17 patients both IIP and lung cancer were present on admission. In
      general, patients with IIP and lung cancer were heavy smokers. In patients with
      IIP and lung cancer, %VC was higher than in those with IIP alone, and 20 cancers
      (90.0%) were in peripheral lung fields. Seventeen patients received anticancer
      chemotherapy, irradiation, or both. Five patients (29.4%) died of respiratory
      failure due to progression of pneumonitis after the therapy. The prognosis for
      patients with IIP and lung cancer was very poor.

PMID- 8741531
TI  - [Clinical evaluation of 201TI single photon emission computed tomography in
      patients with large opacities due to silicosis with bronchogenic carcinoma].
AB  - 201T1 single photon emission computed tomography (201T1 SPECT) was used to
      evaluate 18 patients with large opacities due to silicosis and 22 others with
      bronchogenic carcinoma. An early scan and a delayed scan were obtained and the
      retention index was calculated from the early ratio and the delayed ratio. In
      patients with silicosis, the retention index and the two ratios were
      significantly lower than in the patients with bronchogenic carcinoma (p < 0.01).
      In patients with stable shadows on chest X-ray films due to large opacities of
      silicosis, the delayed ratio was the same as or lower than the early ratio.
      However, in patients with silicosis who had high activity in large opacities, the
      delayed ratio was higher than the early ratio. These results suggest that 201)T1
      SPECT is useful for evaluating the activity of large opacities in patients with
      silicosis and for differentiating large opacities caused by silicosis from those
      caused by bronchogenic carcinoma.

PMID- 8741532
TI  - [Effects of intravenous 2-chloroadenosine on endotoxin-induced acute lung
      injury].
AB  - To assess the effects of 2-chloroadenosine (2CA) on acute lung injury caused by
      endotoxin (lipopolysaccharide), guinea pigs were given 2CA intravenously. Three
      groups were used: saline control, endotoxin control and 2CA+ endotoxin. In the
      endotoxin and 2CA+ endotoxin groups, neutrophils accumulated in bronchoalveolar
      lavage fluid and in lung tissue. However, neutrophil accumulation did not differ
      significantly between the endotoxin and the 2CA+ endotoxin groups. The number of
      macrophages in bronchoalveolar lavage fluid was significantly higher in the
      endotoxin group than in the saline control group, but the difference between the
      saline control and the 2CA+ endotoxin groups was not significant. The lung wet
      dry weight ratio and 125I-albumin lung tissue-plasma ratio, which were used to
      measure acute lung injury, were significantly higher in the endotoxin group than
      in the 2CA+ endotoxin and the saline control groups. However, these ratios did
      not differ between the 2CA+ endotoxin and the saline control groups. These
      results suggest that 2CA attenuated endotoxin induced acute lung injury in guinea
      pigs.

PMID- 8741533
TI  - [Distance walked in 10 minutes, pulmonary function, and pulmonary hemodynamics
      during exercise, in patients with pulmonary emphysema].
AB  - We examined relationships among the distance walked in 10 minutes (10 MD),
      pulmonary function, and pulmonary hemodynamics during exercise on a bicycle
      ergometer, in patients with chronic pulmonary emphysema who had dyspnea of grade
      III to IV on the Hugh-Jones scale. The 10 MD did not correlate significantly with
      desaturation during the 10-minute walk, but it did correlate significantly with
      the percent of predicted maximum voluntary ventilation, and it correlated
      negatively with airway resistance. These findings indicate that ventilatory
      impairment is an important factor limiting 10 MD in these patients. Also 10 MD
      correlated significantly and positively with %DLco; and it correlated negatively
      with the index of pulmonary vascular resistance and with the ratio of the change
      in pulmonary arterial pressure to the change in cardiac index during exercise.
      (delta Ppa/delta CI). These findings indicate that impairment of pulmonary
      circulation may also limit the 10 MD and exercise tolerance in patients with
      chronic pulmonary emphysema.

PMID- 8741534
TI  - [Comparison of biochemical properties of human airway tryptase isolated from
      mucoid sputum with those of lung mast cell tryptase].
AB  - We found a novel trypsin-like enzyme (tryptase) in sputum from patients with
      chronic airway diseases, and named this enzyme human airway tryptase (HAT). To
      clarify its physiological significance in the airway, we compared biochemical
      properties of purified HAT with those of purified lung mast cell tryptase (MCT).
      Studies with model peptide substrates showed that both the HAT and MCT
      preferentially cleaved the COOH-terminal side of arginine residues of certain
      peptides, but substrate specificities to nine synthetic model substrates of HAT
      differed from those of MCT. Effects of protease inhibitors on the two enzymes
      were examined at a concentration of 10 microM. Both the HAT and MCT were strongly
      inhibited by the trypsin inhibitors leupeptin, antipain, and aprotinin. An alpha
      1-protease inhibitor inhibited HAT by 50%, but it did not inhibit MCT. In
      contrast, a secretory leukocyte protease inhibitor strongly inhibited MCT, but
      not HAT. Mucoid sputum from patients with chronic bronchitis contained much more
      HAT than MCT. These differences in biochemical properties between HAT and MCT
      indicate that they play different physiological roles in the airways.

PMID- 8741535
TI  - [Pulmonary dirofilariasis with cavity formation and spontaneous regression].
AB  - A 70-year-old woman was admitted to our hospital for evaluation of a nodular
      shadow and an apparent cavity in the right middle lung field. Transbronchial
      biopsy and percutaneous needle biopsy had failed to result in a diagnosis. Serial
      chest X-ray films revealed slight regression of the nodule without therapy.
      Pulmonary dirofilariasis was diagnosed after open-lung biopsy and Ouchterlony's
      double diffusion test. Cavity formation and spontaneous regression are rare in
      pulmonary dirofilariasis.

PMID- 8741536
TI  - [Bronchobiliary fistula].
AB  - A 57-year-old woman with congenital syphilis had a productive cough, fever,
      cholecystolithiasis, and paralytic ileus. She had a 30-year history of recurrent
      bronchitis accompanied by yellowish serous sputum. A chest radiograph showed
      bilateral infiltrates resulting from aspiration pneumonia, and a reduction in
      volume of the right middle and right lower lobes. After recovering from paralytic
      ileus, she still had fever and biliptysis. Bronchoscopy revealed bile filling the
      right basal bronchi. Emergency laparotomy and throacotomy revealed a gall stone,
      splenomegaly, marked atrophy of the right lobe of the liver, and adhesion between
      the right pleura and the diaphragm. A T-tube cholangiogram showed that the right
      hepatic duct communicated with the right basal bronchus. Despite ligation of the
      right hepatic duct, biliptysis continued. The patient died due to rapidly
      progressing hepatorenal failure. Syphilis gummosa due to congenital syphilis was
      suspected as a cause of the bronchobiliary fistula, but was not confirmed
      pathologically. The surgical specimen showed only nonspecific fibrosis with
      calcification. Bronchobiliary fistula is rare in Japan; we know of only 6 other
      reported cases.

PMID- 8741537
TI  - [Allergic granulomatous angitis with hyper expression of eosinophilic adhesion
      molecules].
AB  - A 43-year-old man who had been treated for bronchial asthma presented with an
      increase in dry coughing and wheezing for one and a half years. In August 1994,
      the patient noted progressive dyspnea on exertion. A chest radiograph revealed
      nodular opacity in the right upper lung field. In November 1994, the patient was
      admitted to Kinki University Hospital with an erythematous rash on the soles of
      both feet. Examination of a specimen biopsy of the skin lesion revealed granuloma
      with eosinophil infiltration. Peripheral blood eosinohilia was noted and a bone
      marrow examination also revealed an increased level of eosinophils. Another chest
      radiograph revedaled that the nodular opacity had disappeared and a new bilateral
      pleural effusion was seen. Eosinophils were the predominant cells in the pleural
      effusion. the patient's condition was further complicated by myocarditis.
      Allergic granulomatous angitis (Churg-Strauss syndrome) was diagnosed and steroid
      therapy was started. After the start of steroid therapy, the skin eruption
      disappered and the myocarditis became less severe. Symptoms of asthma were also
      well controlled. The eosinophils had hypersegmented unclei and increased
      expression of adhesion molecules on their surfaces.

PMID- 8741538
TI  - [Pleural fibroma with a cavity-like air space].
AB  - A 45-year-old man was admitted to the hospital because of an increase in the size
      of an abnormal shadow on chest X-ray films over the preceding 5 years. A chest X
      ray film on admission revealed a round air space in a mass-like shadow in the
      right upper lung field. Results of physical examination, sputum cytologic
      examination, and Ziehl-Neelsen staining were negative. Histopathological
      examination of a percutaneous lung biopsy specimen revealed a benign fibrous
      tumor of the pleura. Thoracotomy revealed a pedunculated tumor arising from the
      visceral pleura at the apical segment of the right upper lobe. A wedge resection
      was done. Histological examination revealed that the tumor consisted of regularly
      shaped spindle cells with densely collagenous tissue. Normal lung tissue was
      found to be invaginated into the tumor tissue. These findings are consistent with
      the radiologic findings.

PMID- 8741539
TI  - [Toxic shock-like syndrome with Streptococcus pyogenes in a pleural effusion].
AB  - A 58-year-old woman was admitted to the hospital because of fever and
      hypotension. That night, shock developed. On the second hospital day, a chest
      roentgenogram showed retention of pleural fluid and the group A-beta hemolytic
      organism Streptococcus pyogenes was detected in the effusion. The toxic shock
      like syndrome was diagnosed. The patient recovered with artificial ventilation,
      administration of antibiotics, and blood purification. In this patient, the type
      of pyrogenic exotoxin was B + C.

PMID- 8741540
TI  - [Tracheal carcinoma causing severe tracheal stenosis].
AB  - A 47-year-old woman was admitted to our hospital because of shortness of breath.
      She had wheezed for a long time before admission. A flow-volume curve showed a
      pattern consistent with a fixed obstruction of the trachea. CT findings also
      revealed severe stenosis of the trachea caused by a tumor mass. Tracheal
      carcinoma was diagnosed after transbronchoscopic biopsy. The patient received
      chemotherapy and radiation therapy concurrently for about six weeks. Her symptoms
      resolved, and a second flow-volume curve had a normal pattern. Tracheal carcinoma
      should be included in the differential diagnosis of airway obstruction. In such
      cases, the flow-volume curve can be useful as a screening test.

PMID- 8741541
TI  - [Pseudoxanthoma elasticum with pulmonary calcification].
AB  - A woman born in 1920 had had multifocal, yellowish nodules on her skin since
      childhood and had been given a diagnosis of pseudoxanthoma elasticum. When she
      was 59-year-old, a diffuse granular shadow was seen on a chest radiograph. When
      she was 74-year-old, she presented with dyspnea on exertion. A thoracoscopic lung
      biopsy was done. Histologic examination of the lung tissue revealed small
      calcified nodules scattered in the alveolar septa. Pseudoxanthoma elasticum is a
      systemic, hereditary disorder that usually affects elastic fibers of the skin,
      eye, and cardiovascular system. It's incidence is quite low: 1 out of 160,000
      1,000,000 population. Very few cases of pseudoxanthoma elasticum with pulmonary
      involvement have been reported, and we know of no previous case in Japan in which
      pulmonary microcalcification was confirmed histologically.

PMID- 8741542
TI  - [Massive hemoptysis caused by disruption of a bronchial aneurysm diagnosed by
      microscopic examination of the resected lung].
AB  - A 29-year-old woman in the 6th month of pregnancy was admitted to our hospital
      because of repeated hemoptysis after an acute respiratory infection. Fiberoptic
      bronchoscopy revealed a polypoid lesion at the orifice of the right B3 bronchus
      and bleeding around the lesion. Bronchial arteriography showed no abnormalities.
      Transcatheter embolization was unsuccessful. Therefore, a right upper lobectomy
      was done. Microscopical examination showed a mass of coagulated blood on the
      mucosal surface of the wall of the B3 bronchus, and a bronchial artery running
      toward the mucosal surface was seen underneath. The mass was thought to be the
      polypoid lesion seen during bronchoscopy. Serial sections showed a bronchial
      aneurysm 1 mm in diameter that had ruptured into the bronchial lumen. Several
      bronchial arteries were located in the propria mucosa in other bronchial
      segments, as observed in the B3 bronchus, but no other focus of bleeding was
      identified. Some cases of hemoptysis of unknown cause may result from similar
      histological alterations.

PMID- 8741543
TI  - [Cytomegalovirus mononucleosis with cytomegalovirus pneumonia in an adult].
AB  - A 29-year-old woman developed fever and sore throat 14 days before admission. Six
      days later she noted the onset of a rash and ten days later she noted a dry
      cough. The chest X-ray film showed no abnormal shadow, but a chest CT scan showed
      a diffuse ground-glass shadow and a 67Ga-scintigram showed abnormal lung uptake.
      The level of anti-cytomegalovirus antibody of the IgM class was high;
      cytomegalovirus mononucleosis was diagnosed and cytomegalovirus pneumonia was
      suspected. Cytomegalovirus DNA was detected in bronchoalveolar lavage fluid by
      the polymerase chain reaction method. We known of no previously reported case of
      cytomegalovirus mononucleosis in which cytomegalovirus DNA was found in
      bronchoalveolar lavage fluid by the polymerase chain reaction method.

PMID- 8741544
TI  - [Swyer-James syndrome with bronchial asthma and recurrent spontaneous
      pneumothorax].
AB  - An 18-year-old woman was admitted to our hospital for treatment of the fifth
      episode of spontaneous pneumothorax. She had a history of repeated pneumonia in
      childhood and mycoplasma pneumonia at 12 years of age. A chest X-ray film
      revealed a left-sided pneumothorax, atelectasis of the left upper lobe, and
      hyperlucency of the left lung. A bronchogram showed poor filling of the
      peripheral bronchi by contrast medium and mild cylindrical bronchiectasis in the
      proximal bronchi. Pulmonary arteriography showed small left pulmonary arteries.
      From these findings, Swyer-James syndrome was diagnosed. This case was
      complicated by bronchial asthma, with eosinophilia, a high level of IgE, and
      airway hyperresponsiveness. Atelectasis, multiple bullae, and bronchial asthma
      had been caused by mycoplasma pneumonia in childhood. Recurrent pneumothorax had
      been caused by emphysematous changes in the bronchioli and by underdeveloped
      pulmonary arteries. Surgery to treat the recurrent spontaneous pneumothorax was
      considered, but was not done because of the risk of relapse and the ventilation
      perfusion imbalance due to the Swyer-James syndrome.

PMID- 8741545
TI  - [Lipoid pneumonia combined with pulmonary nocardiosis caused by inhalation of
      amphotericin-B after renal transplantation].
AB  - A 35-year-old woman was admitted to our hospital because of a fever and a
      productive cough. She had undergone renal transplantation and had taken
      immunosuppressive drugs, a steroid, inhaled amphotericin-B, and pentamidine. She
      was treated with ganciclovir, because infection with cytomegalovirus was
      suspected but her symptoms did not resolve. A chest X-ray film and a computed
      tomogram showed an infiltrative shadow in the right lower lung field. Specimens
      obtained by transbronchial lung biopsy showed lipid-laden macrophages and oil
      droplets in alveolar spaces. Organisms of the genus nocardia were isolated from
      bronchial lavage fluid. The final diagnosis was lipoid pneumonia combined with
      pulmonary nocardiosis. After treatment with Imipenem.cilastatin sodiom, Exacin
      and Sulfamethoxazole.trimethoprim, her symptoms and the infiltrative shadows on
      the chest X-ray film resolved. We believe that this patient had an exogenous
      lipoid pneumonia caused by inhalation of deoxycholic acid in amphotericin-B
      solubilized liquid, in addition to pulmonary nocardiosis.

PMID- 8741546
TI  - [Reduction of homologous blood in elective cardiac surgery with miscellaneous
      autologous blood transfusion--especially with short-term predonation method].
AB  - The efficacy of homologous blood reduction in consecutive elective cardiac
      surgery by four different autologous transfusion methods was described. One
      hundred forty patients were divided into five different groups. No autologous
      blood transfusion in group A (22 cases), intraoperative autotransfusion with Cell
      Saver in group B (24 cases), additional intraoperative hemodilution method in
      group C (25 cases), additional preoperative predonation two weeks before
      operation in group D (15 cases), and predonation one week before operation with
      recombinant human erythropoietin administration in group E (55 cases) were
      performed. In group E, the criterion for patient selection of predonation was
      widely indicated (hemoglobin > 10 g/dl, body weight > 40 kg) and the period of
      the predonation technique was shorter compared with previous reports. The total
      homologous blood transfusion volume and the rate of the patients without
      homologous blood in each groups was 2216 +/- 1888 ml, 14.3% in group A, 2297 +/-
      1789 ml, 4.2% in group B, 774 +/- 1043 ml, 36% in group C, 399 +/- 683 ml, 64.3%
      in group D, 135 +/- 276 ml, and 76.3% in group E, respectively. There were
      significant differences between group A, B or C and group D (p < 0.01), group A,
      B or C and group E (p < 0.001), and group D and group E (p < 0.05) with total
      homologous blood volume and between group A or B and group D (p < 0.01), group A
      or B and group E (p < 0.001), group B and group C (p < 0.05), and group C and
      group E (p < 0.01) with the rate of the patients without homologous blood. The
      reduction of homologous blood volume by patients was 1500 ml by the
      intraoperative hemodilution method, 370 ml by the preoperative prodonation
      technique, and 260 ml with predonation using erythropoietin. Ten of the thirteen
      patient (76.9%) who required homologous blood transfusion in group E had anemia
      (Hb < 12 g/dl) at preoperative blood pooling or postoperative massive bleeding
      (total mediastinal drainage > 1000 ml). Elongation of the predonation period
      before operation or postoperative autotransfusion of mediastinal shed blood and
      intraoperative aprotinin administration in such patients should be considered to
      reduce homologous blood transfusion.

PMID- 8741547
TI  - [Experimental study on resuscitation and salvage of myocardial function (RSMF)
      after normothermic ischemic arrest].
AB  - We studied in anesthetized dogs, the effects of cardiopulmonary bypass with
      normothermic blood, crossclamping of the aortic root, and continuous warm blood
      cardioplegia as a part of circulatory support on the ability of the recovery of
      the deteriorated myocardial function, and compared this method with the
      circulatory support under empty beating stage. Eleven dogs were subjected to the
      deteriorated myocardial function by 30 minute normothermic ischemic arrest and
      myocardial function was measured (baseline function). In 5 dogs (Group A),
      coronary perfusion of 5 ml/kg/min with normothermic blood was established under
      empty beating state. In other 6 dogs (Group B), the aorta was then clamped and 30
      minute infusion of warm blood contained 15 mEq/l of potassium and 2 mEq/l of
      Magnesium was given by 2.5 ml/kg/min as a part of circulatory support. After
      this, aortic clamp was released and coronary perfusion of 5 ml/kg/min with normal
      warm blood followed under empty beating state. Cardiac function was measured at
      the periods of 40, 60 and 90 minutes of circulatory support and compared between
      the two groups. The parameters of left ventricular function (developed pressure,
      dp/dt, -dp/dt) were deteriorated by 30 minutes ischemia by about 50% compared
      with baseline function. In Group a, they improved gradually along with the
      duration of circulatory support and 90 minutes were required to return to the
      baseline function. In Group B, however, their % recovery reached 100% at the
      period of 40 minutes and maintained over 100% thereafter. RSMF could recover
      myocardial function from ischemic damage more quickly and effectively compared
      with circulatory support under empty beating state.

PMID- 8741548
TI  - [The problem of 19 mm St. Jude Medical valve prosthesis in the small aortic
      annuls--19 mm St. Jude Medical valve vs 23 mm St. Jude Medical valve].
AB  - We compared the results of 19 mm SJM aortic valve replacements with those of 23
      mm SJM aortic valve replacements conducted the same period. [Material & Method]
      The subjects were 21 patients who underwent valve replacement with a 19 mm SJM
      prosthesis (the SJM19A group). The age ranged among 16 and 65-year-old, mean of
      51. The body surface area was 1.24 to 1.76 m2, mean of 1.48 m2. The post
      operative follow-up period was 156 months at maximum and 44 months on average. We
      compared the SJM19A group with the SJM23A group by chest X-ray and
      echocardiography. [Results] Two patients in the SJM19A group died soon after
      surgery. Of the other patient, 19 were categorized NYHA I and one in NYHA II
      classification in their late phase. Arrhythmia of Lown IVa developed in one
      patient. The cardio-thoracic ratio decreased from preoperative 60% in the late
      phase after surgery (p < 0.002) in the SJM19A group, although there was no
      significant difference with that in the SJM23A group. Echocardiographic
      improvement in left ventricular hypertrophy was considerable between before and
      late after surgery in the SJM19A group, while it was not significantly different
      between the SJM19A and SJM23A group. The mean value of aorta-left ventricle
      pressure difference in the late stage was 32 mmHg in the SJM19A group and
      significantly different from the value in the SJM23A group (p < 0.001). This
      pressure difference tended to be greater as the follow-up period was progressed,
      while the percentage decrease in the myocardial mass of the left ventricle tended
      to decreased with longer follow-up period. This data suggests that an increasing
      level of aorta-left ventricle pressure difference should raise little problem in
      the mid-term late stage after surgery but possibly cause a serious problem in the
      long term. Clinical observation should be continued over a long period of time
      after surgery.

PMID- 8741549
TI  - [The clinical value of BMIPP on the evaluation of myocardial ischemia and
      metabolism before and after CABG].
AB  - To evaluate the clinical usefulness of BMIPP (15-(p-[125I]-iodophenyl)-3-R, S
      methylpentadecanoic acid), BMIPP and T1 imaging were underwent before and after
      surgery in 25 CABG patients. Preoperatively the demonstrated lesion on BMIPP
      scintigram is almost the same as that on rest-T1 scintigram. A month after CABG,
      the recovery on T1 scintigram was remarkable, however improvement on BMIPP was
      limited. These results suggest that on the evaluation of myocardial ischemia, the
      clinical value of BMIPP is almost the same as that of rest-T1 before CABG. The
      postoperative discrepancy between T1 and BMIPP scintigram suggests that the
      restoration of myocardial circulation does not directly improve myocardial
      metabolism.

PMID- 8741550
TI  - [Traumatic thoracic aortic rupture--diagnosis and surgical repair].
AB  - Fifteen cases of traumatic thoracic aortic rupture (TAR) were treated at St.
      Marianna University Hospital from December 1980 to July 1995. Causes of TAR were
      due to vehicle accidents in 14 patients and fall in one patient. On diagnosis,
      contrast-enhanced CT scan was routinely performed in the patients with blunt
      chest trauma associated with superior mediastinal widening, loss of the aortic
      knob or right shift of the trachea on the initial roentgenogram. When CT scan
      demonstrated specific signs for TAR, pseudoaneurysm formation and/or
      extravasation of the contrast dye, aortography was eliminated before operation.
      As a role, operation was performed on an emergency basis as soon as the diagnosis
      was confirmed. Four cases died due to intrapleural rupture before or immediately
      after thoracotomy. Nine (82%) of the 11 patients in whom operation was completed
      survived and are doing well. In one of the 4 patients who underwent operation
      with simple aortic cross-clamping; paraplegia developed after 30 minutes of
      spinal ischemia. Left heart bypass with the Bio-Pump without heparin or with an
      antithrombin agent, argatroban, was used in recent 6 patients. Use of left heart
      bypass with the Bio-Pump without anticoagulant or with argatroban appears to be
      promising as a safe adjunct in the repair of TAR, preventing fatal bleeding of
      other injured organs.

PMID- 8741551
TI  - [Surgical treatment of aortic dissection with ringed intraluminal graft--late
      results and fate of the false lumen].
AB  - Between April 1981 and March 1992, sixty-nine patients underwent surgery for
      aortic dissection in our hospital and affiliated hospitals. Of them, 48 patients
      who survived the operation were followed up 2 months to 11.8 years (mean: 4.6
      years). We compared the fate of the false lumen and late results in the 31
      patients who underwent ringed intraluminal graft (RIG group) and the 17 patients
      who underwent conventional graft replacement (GR group). To clarify the status
      and severity of the dissected aorta, we devised a scoring system (dissection
      score: DS) to evaluate the long-term changes in the diseased aorta after
      operation. Of 12 patients (25%) who died of late dissection-related
      complications, 10 were in the RIG group and 2 in the GR group. The actuarial
      survival at 5 years was 66 +/- 9% in the RIG group and 88 +/- 8% in the GR group.
      Late dissection-related events (dissection-related death, redissection,
      reoperation) were observed in 17 patients, 14 of whom belonged to the RIG group
      and 3 to the GR group. The dissection-related event-free survival at 5 years was
      51 +/- 10% in the RIG group and 88 +/- 8% in the GR group. In 36 (75%) of the 48
      patients, including 20 (65%) of the 31 patients in the RIG group and 16 (94%) of
      the 17 in the GR group (p < 0.05), it was possible to resect the primary intimal
      tear. The actuarial survival at 5 years was 76 +/- 8% for those 36 cases in which
      resection of the primary intimal tear was possible and 64 +/- 15% for those in
      which resection was not possible. The dissection-related event-free survival at 5
      years was 72 +/- 8% in the former group and 33 +/- 15% in the latter. The
      dissection score (DS) decreased from a pre-operative value of 21.5 +/- 8.4 to
      12.0 +/- 9.3 postoperatively (p < 0.001). A significant decrease in DS was
      observed both in the RIG group and the GR group, in the former from 22.1 +/- 7.2
      to 13.1 +/- 9.3, and in the latter from 19.9 +/- 11.5 to 9.1 +/- 9.2 (p < 0.01).
      The DS for those whose primary intimal tear could be resected was significantly
      decreased postoperatively (pre-operative 20.6 +/- 8.9, post-operative 9.3 +/-
      8.4; p < 0.001); but for those whose primary intimal tear could not be resected,
      there was no difference between the pre- and post-operative DS (pre-operative
      23.4 +/- 7.3, post-operative 18.2 +/- 8.7). The percent reduction in DS (%R) was
      significantly greater in the former group than in the latter one (61% vs. 29%; p
      < 0.02). DS significantly decreased for those with no late dissection-related
      events (from 22.4 +/- 9.2 to 10.9 +/- 8.8; p < 0.001) while for those who
      presented with such events there was no difference between before and after the
      operation (pre-operative 19.0 +/- 5.7, post-operative 14.9 +/- 10.6). The %R in
      those with dissection-related events tended to be lower than that in those
      without such events (33% vs. 58%). Resection of primary intimal tear seemed to be
      important not only to improve operative results in patients with aortic
      dissection but also to improve late results. Depending on the site and size of
      the intimal tear, the ringed intraluminal graft insertion technique often makes
      intimal tear resection impossible. Indications for this surgical technique are
      thus quite limited.

PMID- 8741552
TI  - [Immunosuppressive effect of intravenously injected docosahexaenoic acid on
      single lung allotransplantation in the rat].
AB  - Docosahexaenoic acid (DHA) is an omega 3 polyunsaturated fatty acid. The purpose
      of this study was to evaluate the immunosuppressive effect of intravenously
      injected DHA in rat orthotopically transplanted allograft lung. Based on the
      results of the post-operative treatment, the recipients were divided into four
      groups; Group A (n = 3): normal. Group B (n = 3): isotransplantation with no
      immunosuppressive drugs. Group C (n = 6): allotransplantation with no
      immunosuppressive drugs. Group D-1 (n = 3): allotransplantation with DHA at a
      dose of 0.5 g/kg/day x 2 at 0 and 3 post-operative days (POD). Group D-2 (n = 3):
      allotransplantation with DHA at a dose of 0.5 g/kg/day x 4 at 0, 1, 3 and 5 POD.
      Group D-3 (n = 6): allotransplantation with DHA at a dose of 0.5 g/kg/day x 4 at
      0, 1, 2 and 3 POD. In Groups A and B, F344 rats were used as donor and recipient.
      In Groups C and D, F344 rats were used as recipient and WKAH rats as donor.
      Studies on morphology, bronchoalveolar lavage (BAL) and peripheral blood cells
      were performed at 7 POD after sacrifice. Histological changes in Group D-3 were
      milder than those in Grop C and D-1, but were more progressive than those in
      Groups A and B which showed no rejection. Peripheral leukocytes and
      polymorphonuclear leukocytes counts in Groups D-1, D-2, and D-3 were higher than
      those in Groups, A, B and C. Total cells and lymphocytes of BAL in Groups D-2 and
      D-3 were less than those in Group C, but total cells and polymorphonuclear
      leukocytes of BAL in Groups D-2 and D-3 were more than those in Groups A and B.
      This study suggested that intravenously injected DHA had an immunosuppressive
      effect on the allotransplanted lung in the rats.

PMID- 8741553
TI  - [Early and mid-term results of right gastroepiploic artery grafting in the
      children with Kawasaki disease].
AB  - Thirty-nine children with Kawasaki disease have undergone coronary
      revascularization since 1976. The attrition rate of saphenous vein grafts (SVG)
      was so high that we have used the internal thoracic artery (ITA) as the graft
      since 1984. ITA showed excellent early and mid-term patency. We, however, still
      had to use SVG for the distal portion of right coronary artery (RCA) and left
      circumflex artery (LCx) where ITA was difficult to reach. In 1988, we first
      successfully applied the right gastroepiploic artery (GEA) for revascularization
      to the posterior descending artery of a six-year-old boy. Nine children were then
      bypassed with the combination of ITA and GEA. GEA was anastomosed to the distal
      portion of RCA (7 cases) and the branch of LCx (2 cases). In 4 cases GEA showed
      string sign 1 month after surgery, but the angiographic finding revealed
      improvement after 1 year interval in 2 cases. The patency of GEA grafts was
      excellent after 1 month (100%:9/9) and 1 year (100%:9/9), respectively. The use
      of GEA in addition to ITA as the arterial graft may contribute to the improvement
      of long-term graft patency in revascularization of children with Kawasaki
      disease.

PMID- 8741554
TI  - [A case report--congenital esophago-bronchial fistula with esophageal
      diverticulum].
AB  - Congenital esophago-bronchial fistula with diverticulum is rare, and in Japan
      only 29 cases have been reported. A 59-year-old man had suffered from recurrent
      pulmonary infections and often complained of coughing while drinking water during
      the previous two years. An UGI series for follow-up of gastric ulcer revealed an
      esophago-bronchial fistula, located between the mid-esophagus and B10 of the
      right lung. We resected the diverticulum and the fistulous tract with a partial
      excision of S10. Histological examination revealed that the squamous epithelium
      with the muscularis mucosa of the esophagus was smoothly connected to the
      columnar epithelium of the bronchus. Thus, we diagnosed this fistula as
      congenital, not acquired. Comparison of the previous UGI series before presenting
      symptoms with that performed at this admission showed the lengthening and
      thickening of this congenital fistula during the three-years period. We suspected
      that the influence of acquired factors may cause a congenital fistula to manifest
      various clinical symptoms.

PMID- 8741555
TI  - [A case of small cell carcinoma (oat-cell type) of the esophagus].
AB  - We experienced a case of small cell carcinoma of the esophagus treated by
      operation. A 57-year-old female was examined for a complaint of dysphagia. The
      radiologic and endoscopic examination revealed Borrmann III like tumor (8 cm
      long) at lower esophagus (EiEa). Endoscopic biopsy led to a diagnosis of poorly
      differentiated squamous cell carcinoma. Chest X-ray and chest CT showed no lung
      tumor, no swelling of lymph node and no invasion of esophageal tumor. Lower
      esophagectomy, proximal gastrectomy and esophago-gastrostomy through
      intrathoracic route was performed. Histopathologically, resected tumor was
      diagnosed as small cell carcinoma (Oat-cell type) with rosette formation.
      Grimerius stain revealed negative reaction and immunohistochemical stain by NSE
      monoclonal antibody revealed positive reaction in tumor cells. Histological
      staging was a0, n1(+), M0, P1(zero), stage II. Recurrence at paraaortic lymph
      node occurred in 2 months after the surgery. Chemotherapy (CDDP, 5-FU and
      Leucovorin) was performed, but not effective. She died from multiple metastases
      in 5 months after the surgery (6 months after the diagnosis).

PMID- 8741556
TI  - [A case of solitary sternal metastasis from unknown primary hepatocellular
      carcinoma].
AB  - We report a 61-year-old male patient who was admitted to our hospital for
      treatment of a rapidly growing tumor on the anterior chest. Chest roentgenography
      and chest CT scan showed a mass lesion extending to the subcutaneous tissue over
      the sternum. Although no primary lesion was revealed by subsequent examination
      and needle biopsy, en-bloc resection of the chest wall tumor was performed
      because the patient complained of chest pain and the tumor was growing rapidly.
      Reconstruction of the chest wall was performed using Marlex mesh and bonecement,
      and the skin defect was repaired with a rectus abdominis musculocutaneous flap.
      No complications were observed. The pathological diagnosis of the resected
      specimen was a metastatic sternal tumor from a primary hepatocellular carcinoma.
      However, postoperative evaluation failed to detect the primary lesion in the
      liver. Nine months after the operation, the patient remains alive and well
      without evidence of hepatocellular carcinoma or recurrence. To our knowledge,
      reports of solitary sternal metastasis from unknown primary hepatocellular
      carcinoma seem to be rare.

PMID- 8741557
TI  - [Acute aortic dissection complicated with acute myocardial infarction--a case
      report of successful operation for the case of DOA].
AB  - A 61-year-old woman who suddenly manifested chest and back pain was admitted
      after the diagnosis of acute type A dissection complicated with acute inferior
      myocardial infarction at another hospital. While being transported to our
      hospital by ambulance, her ECG repeatedly demonstrated ventricular fibrillation
      of cardiac arrest. She was in the state of dead on arrival (DOA) when arrived at
      our hospital. ECG demonstrated complete A-V block and cardiac arrest alternately.
      However, soon after right ventricular pacing was done, her blood pressure
      increased and she recovered consciousness. We therefore performed an emergency
      operation. We performed reconstruction of the ascending aorta and right coronary
      bypass grafting, since she had aortic dissection and conus brach avulsion. The
      postoperative course was uneventful.

PMID- 8741558
TI  - [Primary carcinosarcoma of TE lung--a report of two cases].
AB  - Carcinosarcoma is a rare lung tumor and accounts for less than 0.3% of primary
      lung malignancies. Since the first description by Kika in 1908, only 36 cases
      with this kind of tumor have been appeared in the Japanese literatures by 1993.
      This report presents our surgical experiences of two cases with carcinosarcoma of
      the lung confirmed by pathological examination. Case 1: 64-year-old male
      underwent left lower lobectomy with lymph node resection. The patient has been
      well 27 months after the operation without tumor recurrence. Case 2: was a 75
      year-old male, who underwent left upper lobectomy, partial resection of left
      lower lobe (S6) with lymph node resection. This patient died of aspiration
      pneumonia 90 days after successful resection of the tumor. In both patients,
      resected lung tumors were diagnosed to be true carcinosarcoma by
      histopathological examinations. True carcinosarcoma is defined to contain both
      cancelous and sarcomatous elements. Sarcomatous elements may differentiate into
      rhabdomyosarcoma, osteosarcoma and so on, or they may have non-epithelial
      elements demonstrated by electron microscopy or immunohistochemical studies. We
      reviewed the 36 cases with carcinosarcoma of the lung reported in Japanese
      literatures with special consideration of their histopathological findings. The
      prognosis of the patients with this rare tumor is also discussed according to the
      TMN stages.

PMID- 8741559
TI  - [A case of saccular aneurysm of the coronary artery].
AB  - A 42-year-old man with chest oppression was diagnosed as having a saccular
      aneurysm of the coronary artery by cardiac catheterization. At the time of
      operation on April 26, 1993, the aneurysm, measured 15 mm in diamer, and arose
      from the proximal segment of the first septal branch of the left anterior
      descending coronary artery. Several coronary arteriovenous fistulae from the
      aneurysm to the pulmonary artery were also noted. The stem of the aneurysm and
      the coronary arteriovenous fistulae were ligated and the aneurysm was resected.
      We considered the etiology to be mainly arteriosclerosis on the basis of the
      aneurysm pathology. And this aneurysm was also considered to have congenital
      factors because of the existence of arteriovenous fistulae. There were no
      symptoms after the operation and he was discharged at 24th postoperative day. Now
      he continues to do well.

PMID- 8741560
TI  - [Ventricular septal perforation due to weak blunt chest trauma. A case report].
AB  - Traumatic ventricular septal perforation (VSP) is a rare type of heart injury.
      This case report describes a 72-year-old Japanese woman who got VSP secondary to
      weak blunt chest trauma on a train. A two-dimensional color doppler
      echocardiography and cardiac catheterization study revealed a VSP at muscular
      portion near the apex. On the 48th day following injury, she was performed a
      patch closure through left ventriculotomy under cardiopulmonary bypass. The
      patient was discharged uneventfully.

PMID- 8741561
TI  - [Re-do Fontan operation--a case report].
AB  - A 32-year-old woman developed heart failure. She had received Glenn operation 26
      years ago and Fontan operation using valved conduit (Bjork-Shiley: 21 mm) seven
      years ago for tricuspid atresia type 1b. She underwent extirpation of the struck
      prosthetic valve. Neither graft stenosis nor pressure gradient between the right
      atrium and the pulmonary artery were observed on postoperative right
      arteriography. Sternotomy on redo Fontan operation should be carefully performed
      for preventing breaking down the implanted valved conduit. Though the prosthetic
      valve was not necessary on redo Fontan operation, anticoagulation after operation
      should be done.

PMID- 8741562
TI  - [A case of spontaneous ruptured of the esophagus managed with pedicled omental
      covering].
AB  - We experienced a case of spontaneous rupture of the esophagus which was
      successfully managed by suture of the ruptured site and pedicled omental
      covering. A 47-year-old male was referred to our department in unstable condition
      60 hours after the onset of acute symptoms. Upon presentation to the hospital,
      the patient was in shock and complained of severe chest pain and dyspnea, the
      onset of which followed vomiting after consumption of alcohol. A diagnosis of
      spontaneous rupture of the esophagus was made on the basis of the history of the
      episode and chest X-ray and chest CT findings. After construction of a pedicled
      omentum created during laparotomy, left-sided thoracotomy and debridment of the
      mediastinum was performed, which was seen to contain necrotic tissue and
      purulental fluid. The site of esophageal rupture, nearly 3 cm in length, was
      sutured shut and reinforced with a pedicled omental covering, the postoperative
      course was uneventful, and oral intake was resumed 20 days following the surgery.
      The pedicled omental covering procedure was useful for reinforcing sutures at the
      site of rupture and for control of infection in this patient for whom institution
      of surgical therapy for spontaneous esophageal rupture was delayed following the
      acute onset of symptoms.

PMID- 8741563
TI  - [A case of malignant mediastinal germ cell tumor benefited by multidisciplinary
      therapy].
AB  - A 24-year-old man admitted to our hospital because of hemoptysis and left
      precordial pain. Chest X-ray and chest CT scan showed a mass in the left
      anterosuperior mediastinum. Laboratory examination revealed elevated levels of
      AFP (550 ng/ml), which were highly indicative of malignant germ cell tumor.
      Imaging examination indicated that the mass was resectable, so surgery was
      performed prior to chemotherapy. Histological examination revealed an admixture
      of seminoma, immature teratoma, embryonal carcinoma and yolk sac tumor. Because
      the resection performed was incomplete, the patient received three courses of
      combination chemotherapy consisting of CDDP, VP-16 and BLM and 40 Gy irradiation.
      The serum level of AFP was normal after one course of combination chemotherapy.
      The patient has shown no sign of recurrence for 3 years since surgery.

PMID- 8741564
TI  - [Intravascular invasion of a thymoma from the thymic vein to the right atrium--a
      case report].
AB  - A 43-year-old woman with a complaint of facial swelling was admitted to our
      hospital. A chest roentgenogram revealed a mass in the mediastinum. Chest CT and
      MRI demonstrated a mass in the anterior mediastinum protruding into the superior
      vena cava (SVC) and right atrium. A diagnosis of thymoma was made by needle
      biopsy. The patient underwent surgery without preoperative treatment. The tumor
      extended across the capsule of hte thymic gland and a polypoid growth of tumor
      reached the right atrium through the lumen of the thymic and left brachiocephalic
      veins and the SVC. No direct infiltration into the SVC or pericardial cavity was
      observed. Under cardiopulmonary bypass, the tumor was resected with the left
      brachiocephalic vein, SVC, and the upper third of the right atrium. The SVC was
      reconstructed using an EPTFE graft. Histopathologic examination demonstrated a
      predominantly epithelial cell thymoma. Adjuvant chemotherapy was performed, and
      no recurrence has been recognized for 3 years postoperatively.

PMID- 8741565
TI  - [A case of extended surgery in acute aortic dissection by perfusion into extra
      anatomic bypass].
AB  - Total aortic arch replacement creates various problems involving surgical
      techniques, myocardial protection and perfusion methods. The most important
      problem during this procedure is cerebral ischemia. We developed a technique to
      prevent this problem by bypass grafting through the right axillo-left external
      carotid-left axillary artery and perfusing the brain continuously through the
      side branch attached to this bypass graft. A 62-year-old man with acute aortic
      dissection underwent ascending aorta and total aortic arch replacement using this
      alterative perfusion method. No cerebral dysfunction was seen in this case. The
      advantages of this method are as follows: there is no time limit required even
      for total aortic arch replacement; adequate and reliable anastomosis is possible;
      the dissecting aortic branches are not touched directly; it is possible to
      prevent cerebral infarction caused by mural thrombus and pieces of
      atherosclerotic plaque by clamping the aorta and aortic arch branches; and it is
      possible to prevent air embolism.

PMID- 8741566
TI  - [A case of hamartoma originated from the chest wall].
AB  - Hamartoma originated from the chest wall is rare. All reported cases are infant's
      ones. A 16-year-old man was admitted to our hospital because of chest pain and
      abnormal shadow in routine chest X-ray film. Thoracotomy was performed under the
      diagnosis of pulmonary sequestration in the left apical region. However, the
      operation revealed a tumor originated from the chest wall, which was diagnosed
      hamartoma by histological examination. Re-operation was required because of
      hemothorax caused by residual tumor. Second and third ribs were resected with
      residual tumor. There is no evidence of recurrence one year after the second
      operation.

PMID- 8741567
TI  - [A case of primary tissue failure in aortic bioprosthesis due to pannus
      formation].
AB  - A 22-year-old man, who had received aortic valve replacement with a 21 mm of
      Carpentier-Edward S.A.V Bioprosthesis for aortic regurgitation at 19 years of
      age, was readmitted to our hospital because of a new systolic murmur and his
      chest roentgenogram showed remarkable cardiomegaly. Cardiac catheterization
      showed a 55 mmHg pressure gradient across the bioprosthesis. Under the diagnosis
      of primary tissue failure, reoperation was undergone. At reoperation, the sewing
      ring and leaflets of the prosthesis were covered with pannus, which adhered to
      leaflets, and the thickness of these leaflets was seen. It was thought that these
      changes caused aortic stenosis. Primary tissue failure due to pannus formation
      has been reported a little, but if bioprosthesis is implanted in the supra
      annular position, pannus formation may occur because cusps of bioprosthesis are
      attached to the host's annulus.

PMID- 8741568
TI  - [Surgical experience of two different types of unroofed coronary sinus].
AB  - We experienced two cases with uncommon unroofed coronary sinus. The first
      patient, a 55-year-old man, had a partially unroofed mid-portion of the coronary
      sinus. His symptoms and physical state were similar to that of atrial septal
      defect (ASD). Echocardiogram and angiogram revealed that the coronary sinus (CS)
      communicated with the left atrium (LA). We confirmed that CS had an enlarged
      orifice and lacked a part of its roof through the right atriotomy and the
      atrioseptotomy. We directly closed the defect between the LA and the CS. His
      postoperative course was satisfactory. The second patient, a 46-year-old man,
      showed mild cyanosis. He had a completely unroofed CS with left superior vena
      cava (LSVC), absent inferior vena cava (IVC) and hemiazygos continuity. The LSVC
      directly drained to the LA, and the CS was absent. A part of the posterior wall
      of the LA was like a groove which laid from the orifice of the LSVC to the
      coronary sinus ASD. The roof of this groove was covered with fibrous tissue,
      which was shaped like a network structure. We thought that this network was a
      residue of the septum between the CS and the LA. Thus we resected this structure,
      and reconstructed the roof by equine pericardial patch to drain the venous blood
      from the LSVC to the right atrium. Anomaly in the patient may be the transitional
      type between the completely unroofed CS and the partially unroofed CS.

PMID- 8741569
TI  - [Successful surgical treatment of intraoperative aortic dissection complicating
      aortic valve replacement].
AB  - A 74-year-old man underwent standard aortic valve replacement. The aortotomy was
      closed by use of strips of Teflon felt because of somewhat friable thin aortic
      wall. After the termination of cardiopulmonary bypass, aortic cannulation site
      was carefully sutured enforcing with a piece of pericardium, since some bleeding
      persisted. The intraoperative diagnosis of acute aortic dissection (Stanford type
      A) was made with transesophageal echocardiography. Since extension of the
      dissection toward the aortic root was hardly possible due to the Teflon felt
      enforced aortotomy closure, further surgical intervention was not considered at
      this time. Thiry-two hours later after admission to CCU, sudden bleeding through
      the mediastinal tube prompted the patient back to OR for exploration Bleeding was
      noted from the posterior wall of the ascending aorta. Ascending aorta and
      transverse arch were significantly enlarged with notable discoloration. With the
      aid of extracorporeal circulation and selective cerebral perfusion, the total
      graft replacement of the ascending aorta and aortic arch was performed. The
      intimal tear located at the aortic cannulation site. The postoperative course was
      uneventful. Prompt recognition and appropriate surgical management are necessary
      to improve patient outcome.

PMID- 8741570
TI  - [Veno-arterial bypass and intraaortic balloon pumping for profound right heart
      failure--a case report of perioperative right heart infarction].
AB  - A combination of veno-arterial bypass (VAB) and intraaortic balloon pumping
      (IABP) was applied to a 54-year-old male patient whose right heart function was
      severely damaged immediately following aortic valve replacement. A diagnosis of
      perioperative myocardial infarction was made with findings of severe hypokinesis
      of the right heart, new Q wave with ST elevation, and increased cardiac escaping
      enzyme. The VAB was maintained wih a pump flow rate of 2.0-2.5 L/min. The system
      was exchanged to the second one 42 hours after the surgery. According to repeated
      on/off testing, the VAB was successfully weaned on the 5th postoperative day
      followed by weaning IABP on the 6th postoperative day. This case report shows a
      recovery from isolated right heart failure by an immediate switching from a
      cardiopulmonary bypass to VAB and IABP.

PMID- 8741571
TI  - Location of two photoaffinity-labeled sites on the ligand-binding domain of
      retinoic acid receptor alpha.
AB  - Retinoic acid receptors (RARs) consist of six domain structures. The C-terminal
      region (D/E/F-domains) is involved in ligand binding, dimerization, and ligand
      dependent transactivation. Structural information about RARs is required for
      understanding its complex function. A photoreactive retinoid denoted as ADAM-3,
      which was designed as the result of comparison of two fluorescent retinoids (DAM
      3 and DAM-15), was synthesized and used for photoaffinity labeling of recombinant
      protein MBP-RAR alpha/E. The photoaffinity-labeled site was determined by an
      endoprotease combination method which utilizes four endoproteinases in a two
      phase digestion procedure. Two major labeled fragments were detected in each
      digestion, and the results of two-phase digestion allowed identification of the
      labeled residues as being located within residues 492-510 and 585-594, which
      correspond to 288-306 and 381-390 in human RAR alpha, respectively.

PMID- 8741572
TI  - Lipid peroxidation in egg phosphatidylcholine liposomes: comparative studies on
      the induction systems Fe2+/ascorbate and Fe(3+)-chelates/xanthine-xanthine
      oxidase.
AB  - Two typical systems of lipid peroxidation in egg yolk phosphatidylcholine (egg
      PC) liposomes were compared: an enzymic system involving superoxide (O2)
      generated by xanthine (X), xanthine oxidase (XO) and Fe(3+)-chelates (Fe(3+)-ADP
      and Fe(3+)-EDTA), and a non-enzymic system involving ascorbic acid (ASA) and
      Fe2+. These two systems exhibited a different pH-dependence: the rate in the
      enzymic system was maximal at pH 8-8.5, whereas that in the non-enzymic system
      was high below pH 7.4 and low above pH 7.6. The rates of lipid peroxidation
      differed with the membrane charge, and this charge-dependent phenomenon differed
      in the two peroxidation systems: in the Fe(3+)-chelates/X-XO-system, the rate was
      slow in neutrally charged egg PC liposomes and rapid in egg PC liposomes
      containing negatively charged dicetylphosphate (DCP) or positively charged
      stearylamine (SA), whereas in the Fe2+/AsA-system, the rate was rapid in neutral
      egg PC liposomes but no lipid peroxidation occurred in egg PC liposomes charged
      with DCP or SA. The decomposition rate of the hydroperoxide of PC (PC-OOH)
      incorporated into dimyristoyl-phosphatidylcholine (DMPC) liposomes differed
      depending on the membrane charge in the two systems and this charge-dependence of
      the rates correlated well with that of the initiation rate of lipid peroxidation
      dependent on membrane charge. In the Fe2+/AsA-system, lipid peroxidation depended
      on the endogenous presence of PC-OOH, and the amounts of PC-OOH required for
      initiation of the reaction differed depending on the membrane charge. However, in
      the Fe(3+)-chelates/X-XO-system, lipid peroxidation occurred very slowly in the
      absence of PC-OOH, but rapidly in its presence.

PMID- 8741573
TI  - Proteolysis of human tumor necrosis factor (TNF) by endo- and exopeptidases:
      process of proteolysis and formation of active fragments.
AB  - Recombinant human tumor necrosis factor (TNF) was digested with endopeptidases
      under mild conditions. Incubation of the TNF (155-amino-acid TNF) with trypsin,
      Staphylococcus aureus V-8 protease or chymotrypsin initially released small
      peptides derived from the amino (N)-terminal region of TNF, but did not release
      peptides from the carboxyl (C)-terminal region. The TNF was resistant to
      carboxypeptidases A and Y under a non-denaturing condition, but in the presence
      of urea or sodium dodecyl sulfate the C-terminal amino acid was released
      quantitatively by these peptidases. These results indicate that the N-terminal
      region of the TNF molecule is accessible to protease, while the C-terminal region
      is not susceptible to degradation. When the TNF was incubated with seven kinds of
      endopeptidases, its activity rapidly disappeared. At an early stage of the
      degradation, one active fragment was detected among the fragments produced with
      trypsin or pronase P, but no active fragments were detected on the degradation
      with the other peptidases. The active fragment was a fragment lacking the four N
      terminal amino acid residues of the TNF. These results suggest that TNF is
      initially degraded at the N-terminal region by an endopeptidase and loses its
      activity as the degradation proceeds.

PMID- 8741574
TI  - Thiopalmitic acid-mediated Fe(III)-nitrilotriacetate reduction and lipid
      peroxidation.
AB  - The mechanism of the antioxidant action of thiopalmitic acid (SH-Pal) was
      examined in an in vitro system measuring ferric (Fe(III)-nitrilotriacetate (NTA)-
      and Fe(III)-NTA/ascorbic acid (AsA)-induced lipid peroxidation of rat liver
      phospholipid liposomes and microsomes. The extent of lipid peroxidation was
      determined by measuring thiobarbituric acid reactive substances (TBARS). SH-Pal
      and glutathione (GSH) scarcely stimulated the Fe(III)-NTA-induced lipid
      peroxidation in contrast with the mode of action, being similar to those produced
      by reducing-agent antioxidants such as cysteine and AsA. SH-Pal reduced iron
      similar to the action produced by AsA and cysteine, but not that of GSH under the
      same conditions. Also, the reduction of iron by SH-Pal did not exhibit a pH
      dependency. Similarly, microsomal lipid peroxidation and oxygen consumption
      induced by Fe(III)-NTA/AsA were inhibited by the addition of SH-Pal in a time and
      dose dependent fashion, but GSH and cysteine exhibited a lower protective action.
      Time course studies on TBARS formation and oxygen consumption indicated the
      ability of SH-Pal to inhibit initiation and propagation reactions. Moreover, the
      microsomal lipid peroxidation induced by Cumene hydroperoxide (CumOOH) was
      progressively suppressed by the addition of increasing amounts of SH-Pal. These
      findings suggest that the antioxidant action of SH-Pal is partly due to complete
      reduction of iron at a faster rate and inhibition of oxygen consumption during
      the progress of the peroxidation. Further, SH-Pal has a protective action against
      free radical damage by hydroperoxy radical.

PMID- 8741575
TI  - Allelotype analysis in mouse hepatocellular carcinomas; frequent homozygous
      deletion of mouse homolog of p16/CDKN2 gene on chromosome 4 in culture.
AB  - Because allelotype analysis of many tumors has been important in the
      identification of new tumor suppressor genes, here we have analyzed
      hepatocellular carcinomas (HCCs) derived from F1 hybrid mice between C3H and MSM
      in detail. The analysis showed no allelic loss in primary HCCs, while the loss
      was detected in tumor cell lines established from HCCs. Recently, a candidate
      tumor suppressor gene termed p16/CDKN2, which was located near the interferon
      gene cluster on human chromosome 9p21, was identified by virtue of its frequent
      homozygous deletion in cell lines derived from many different tumor types. Since
      frequent allelic imbalances in the D4MIT9 locus and loss of heterozygosity in the
      alpha-interferon gene which was located near the mouse homolog of p16/CDKN2
      (mouse p16) gene were detected in tumor cell lines, we investigated homozygous
      deletion of the mouse p16 gene by the comparative multiplex PCR method. The
      analysis revealed frequent homozygous deletion of the gene in thirteen of the
      tumor cell lines (13/25, 52%), but not in primary HCCs (0/25, 0%). These data
      indicate that gene deletions including the mouse p16 gene on chromosome 4 in
      tumor cell lines occur during the culture and that allelic imbalances are
      uncommon in mouse primary HCCs. Our results suggest that mouse p16 plays an
      important role in mouse hepatocarcinogenesis in vivo in progression or
      immortalization in vitro.

PMID- 8741576
TI  - Effects of methyl 9(or 10)-hydroxy-10(or 9)-mercaptostearate and hexadecanethioic
      S-acid on cupric ion- or 2,2-azo-bis(2-amidinopropane) dihydrochloride (AAPH)
      induced oxidation of low density lipoprotein.
AB  - The preventive effects of two antioxidants, methyl 9(or 10)-hydroxy-10 (or 9)
      mercaptostearate (SH-S) and hexadecanethioic S-acid (thiopalmitic acid, SH-Pal)
      against the oxidative modification of low density lipoproteins (LDL) induced by
      cupric ion or a water soluble initiator of peroxyl radicals, 2,2-azobis(2
      amidinopropane) dihydrochloride (AAPH), were studied by measuring thiobarbituric
      acid-reactive substances (TBARS). SH-S acted as an effective antioxidant in the
      oxidative modification of LDL induced by either cupric ion or AAPH.
      Interestingly, SH-S completely inhibited the formation of fluorescence products
      and decreased both the fluorescence and alpha-tocopherol content in LDL induced
      by cupric ion, and reduced 1,1-diphenyl 2-picrylhydrazyl (DPPH) used as a stable
      free radical model. The antioxidative effect was effectively prevented by the
      addition of increasing amounts of N-ethylmalemide (NEM) to the system. SH-Pal
      also inhibited the cupric ion-induced LDL oxidation, but showed little inhibitory
      effect on the AAPH-induced LDL oxidation. Moreover, SH-Pal was reduced to
      palmitic acid during the AAPH-induced LDL oxidation. These findings indicate that
      SH-S protects against oxidative damage of LDL in vitro, and that it acts as a
      free radical in peroxidation. In addition, this study shows that SH-Pal doesn't
      act as an efficient antioxidant in AAPH-induced lipid peroxidation.

PMID- 8741577
TI  - Calcium signals in helper T cells after interaction with antigen-specific and
      antigen-nonspecific B cells.
AB  - By confocal fluorescence microscopy we have studied the rises of the
      intracellular free calcium ion concentration ([Ca2+]i) in helper T cells (KLH
      specific, I-Ak-restricted Th1 cells, 28-4) after interaction with antigen
      specific and antigen-nonspecific B cells (antigen-presenting cells). Antigen
      specific and antigen-nonspecific B cells were prepared by the preincubation of
      TNP (trinitrophenol)-specific B cell hybridomas (TP67.21 I-Ak) with TNP
      conjugated KLH and KLH alone, respectively. Calcium signals in Th1 cells (28-4)
      were induced by antigen-specific B cells one hundred times more efficiently as
      those by antigen-nonspecific B cells. Herbimycin A, a tyrosine kinase inhibitor,
      suppressed the former signals but not the latter. These results indicated that
      tyrosine phosphorylation was involved in the antigen processing of antigen
      specific B cells but not in the processing of antigen-nonspecific B cells.

PMID- 8741578
TI  - A sennoside-hydrolyzing beta-glucosidase from Bifidobacterium sp. strain SEN is
      inducible.
AB  - Bifidobacterium sp. strain SEN was isolated and characterized by hydrolytic
      conversion of sennosides to sennidins (Akao et al., Appl. Environ. Microbiol.,
      60, 1041 (1994)). The sennoside-hydrolyzing capacity of the strain SEN was
      disappeared following the addition of glucose to the media in spite of good
      bacterial growth and potent activity hydrolyzing p-nitrophenyl beta-D
      glucopyranoside (pNPG). In a fructose-containing medium, no such suppressing
      effect was shown. Following a 10 h incubation in 50 mM potassium phosphate buffer
      (pH 7.4), the sennoside-hydrolyzing activity of the bacterium increased, dose
      dependently, with the addition of sennoside B. Inhibition of the substrate
      induced increase in sennoside-hydrolyzing activity was observed following the
      addition of some antibiotics (chloramphenicol, streptomycin, and rifampicin). In
      particular, chloramphenicol completely inhibited the increase of sennoside
      hydrolyzing activity while 38% pNPG-hydrolyzing activity remained. It is
      suggested that the strain SEN produces two different beta-glucosidases of which
      the sennoside-hydrolyzing enzyme is inducible. In addition, the glucosides pNPG,
      esculin, salicin, or amygdalin stimulated the induction of the sennoside beta
      glucosidase, but less markedly than sennoside. Sennidin A or sugars (glucose,
      fructose, cellobiose, or maltose) did not induce the enzyme.

PMID- 8741579
TI  - Purification and characterization of a novel sennoside-hydrolyzing beta
      glucosidase from Bifidobacterium sp. strain SEN, a human intestinal anaerobe.
AB  - A novel beta-glucosidase, which is inducible and capable of catalyzing the
      hydrolysis of sennosides, was purified from Bifidobacterium sp. strain SEN with
      Triton X-100 solubilization and DEAE-cellulose column chromatography, by which
      hydrolytic activities toward sennoside B, 4-methylumbelliferyl beta-glucoside
      (MUG), and p-nitrophenyl beta-glucoside (pNPG) were obtained together in the same
      eluted fractions. The activity was stable against detergents such as sodium
      dodecyl sulfate (SDS) and Triton X-100, but was denatured by SDS and beta
      mercaptoethanal when heated. The final preparation was shown to be nearly
      homogeneous on SDS-polyacrylamide gel electrophoresis (PAGE) either after the
      enzyme was denatured or when it was not denatured. In the non-denaturing SDS
      PAGE, a single protein band hydrolyzed MUG on the gel. In the denaturing SDS
      PAGE, the subunit mass of the enzyme was estimated to be 110 kDa. The enzyme was
      optimally active at pH 6.0 for hydrolysis of sennoside B and MUG. Km values for
      sennoside B and MUG are 0.94 and 0.53 mM, respectively. The enzyme also catalyzed
      the hydrolysis of pNPG, amygdalin, geniposide and salicin. It was less active
      against methyl beta-glucoside and incapable of hydrolyzing cellobiose. The beta
      glucosidase activity was inhibited by deoxynojirimycin and p
      chloromercuribenzenesulfonic acid, but was less susceptible to several metals
      (FeSO4, ZnCl2, and CuSO4), and 5,5'-dithio-bis(2-nitrobenzoic acid).

PMID- 8741580
TI  - Significance of the therapeutic range of serum theophylline concentration in the
      treatment of an attack of bronchial asthma.
AB  - The purpose of this study was to evaluate the accuracy of the recommended
      theophylline therapeutic range in the treatment of acute airway obstruction.
      Twenty seven patients (20 to 64 years) with acute asthma attack were given
      aminophylline intravenously to obtain a theophylline concentration between 10 and
      20 micrograms/ml. Peak expiratory flow rates (PEFR) and serum theophylline
      concentrations were measured before and after aminophylline injection. When a
      marked improvement was not seen after aminophylline injection, the treatment was
      followed by inhalation of a beta-agonist and intravenously administered
      hydrocortisone. In order to clarify the relationship between theophylline
      efficacy at a therapeutic level and PEFR, as measured before aminophylline
      administration, the patients were classified into four groups. Group A (n = 7):
      asthma attack persisted regardless of treatment with aminophylline, beta-agonist
      and hydrocortisone, group B (n = 7): asthma attack improved by aminophylline,
      beta-agonist and hydrocortisone, group C (n = 6): asthma attack improved by both
      aminophylline and beta-agonist, group D (n = 7): asthma attack improved by
      intravenous aminophylline alone. The means (+/- S.E.) PEFR before aminophylline
      administration were 94.3 +/- 11.31/min in group A, 114.3 +/- 10.01/min in group
      B, 196.7 +/- 22.21/min in group C, and 220.0 +/- 12.51/min in group D,
      respectively. There were significant differences in PEFR between the A and C, A
      and D, B and C, and B and D groups. These findings suggest that theophylline
      efficacy is not expected in patients with low PEFR (less than 2001/min) at the
      time of treatment of an attack, even if a therapeutic theophylline concentration
      was obtained.

PMID- 8741581
TI  - Lipid peroxidation in gastric mucosal lesions induced by indomethacin in rat.
AB  - The peroxidation of lipids and changes in the activities of related enzymes in
      the gastric mucosa were studied in a rat model of gastric mucosal injury induced
      by the nonsteroidal anti-inflammatory drug indomethacin. The area of gastric
      erosion and the amount of thiobarbituric acid reactive substances (TBARS) in
      gastric mucosa were significantly increased beginning 4h after administration of
      indomethacin. Xanthine oxidase (XOD) activity in the gastric mucosa also
      increased immediately after administration of the drug. Although XOD activity was
      significantly suppressed by allopurinol treatment, the induction of gastric
      mucosal injury and the increase of TBARS in the gastric mucosa were not.
      Myeloperoxidase (MPO), a marker enzyme of leukocytes, was unaffected by
      indomethacin administration. But the depletion of polymorphonuclear leukocyte
      (PMN) counts induced by an injection of anti-rat PMN antibody inhibited both the
      injury and the increase in TBARS. Indomethacin activated PMN in peripheral blood
      at 30mg/kg per as and enhanced release of oxygen radicals from PMN in peripheral
      blood. As compared with the XOD system, the generation of oxygen free radicals
      may derived mainly from activated PMN. On the other hand, superoxide dismutase
      (SOD) and glutathione peroxidase (GSH-px) were reduced by the administration of
      indomethacin. Decreases in SOD and GSH-px activity in gastric mucosa may
      aggravate mucosal injury by free radicals and lipid peroxidation.

PMID- 8741582
TI  - Differential effect of UV-B and UV-C on DNA damage in L-132 cells.
AB  - Ultraviolet radiation is known to induce skin cancer. The induction of DNA damage
      caused by UV-B and UV-C was investigated using cultured L-132 cells. DNA strand
      breaks assayed by the alkaline elution procedure occurred in a dose-dependent
      manner, the extent of the strand breaks were inversely well correlated with the
      number of viable L-132 cells after 24 h incubation. About a 10-fold dose of UV-B
      irradiation was required to induce a similar degree of strand breaking to that
      induced by UV-C. Similarly about a 10-fold dose of UV-B was required to produce a
      similar amount of pyrimidine dimers, such as cyclobutane-type dimers and
      pyrimidine-(6-4)-pyrimidone photoproducts, which were determined by ELISA using
      the specific monoclonal antibody, to that produced by UV-C. Strand breaks induced
      by UV-B, however, were not fully repaired in viable cells remaining after
      incubation of cells for a longer period of time, although UV-C-induced strand
      breaks were repaired in a time-dependent manner. Furthermore, an experiment with
      a cell-free system, where the induction of strand breaks by repair enzymes did
      not take place, indicated that UV-B caused significantly more direct DNA strand
      breaks than that caused by one-tenth the dose of UV-C. The data shown here
      suggest that UV-B-induced DNA damage is mediated, at least in part, via a
      different mechanism from the UV-C induced one.

PMID- 8741583
TI  - Spectroscopic analysis of charge transfer complex formation and peroxidase
      inhibition with tricyclic antidepressant drugs: potential anti-thyroid action.
AB  - Inspection of the chemical structures of tricyclic antidepressant drugs indicates
      that they might interfere with the synthesis of thyroid hormones. This iatrogenic
      potential was demonstrated in vitro by the spectrophotometric detection in both
      the visible and UV regions of the formation of a complex between antidepressants
      and iodine. The values of Kc, the formation constant of the drug-iodine complex,
      were calculated. The concentration of antidepressant which led to a 50%
      inhibition (IC50) of horseradish peroxidase was also determined. The anti-thyroid
      activity of drugs can be evaluated from these two parameters, Kc and IC50. The
      results were compared to those obtained with methimazole, a reference anti
      thyroid agent. Antidepressants derived from imipramine appeared to have anti
      thyroid activity. This result is now awaiting confirmation in animal experiments.

PMID- 8741584
TI  - Modulation of the pharmacokinetics of 5'-deoxy-5-fluorouridine and 5-fluorouracil
      in rats by oral co-administration of acyclothymidine.
AB  - The effect of an inhibitor of pyrimidine nucleoside phosphorylase (PyNPase),
      acyclothymidine (AcyT), on the pharmacokinetics of 5'-deoxy-5-fluorouridine (5'
      DFUR) and 5-fluorouracil (5-FU) was investigated in an oral co-administration of
      5'-DFUR and AcyT in rats. AcyT increased the maximal plasma concentration (Cmax)
      and apparent absorption rate constant (ka) of 5'-DFUR, as expected, but the
      increase in AUC (area under the curve) was not significant. It was expected that
      AcyT would only inhibit the phosphorolytic degradation of 5'-DFUR to 5-FU, but
      the effect was more evident on the pharmacokinetic parameters of 5-FU than on
      those of 5'-DFUR. AcyT also increased AUC and Cmax of 5-FU when orally co
      administered with 5-FU. An inhibitory effect of AcyT on the enzymatic degradation
      of 5-FU in rat liver and intestinal extract was investigated. AcyT inhibited the
      degradation in intestinal extract but not in the liver. The result suggests that
      orally administered AcyT affects the pharmacokinetics of 5-FU partly by
      inhibiting 5-FU degradation in the process of intestinal absorption as well as by
      acting as an inhibitor of PyNPase.

PMID- 8741585
TI  - Effect of clarithromycin on the bioavailability of cyclosporin in rats.
AB  - This study was conducted to determine the effect of clarithromycin (CAM) on the
      bioavailability of cyclosporin (CYA) in rats, and to compare its effect with that
      of erythromycin (EM). The area under the blood CYA concentration-time curve
      (AUCi.v.) values after intravenous administration of CYA (2 mg/kg) in combination
      with CAM or EM (100 mg/kg, p.o.) were significantly increased compared with those
      of CYA alone, suggesting that there was metabolic inhibition of CYA in the liver
      by CAM or EM. The time to reach the peak concentration after oral administration
      of CYA (10 mg/kg) tended to be longer with increasing doses of both CAM and EM
      (10 and 100 mg/kg, p.o.). Each AUCp.o. value for the CAM or EM coadministration
      group, except the EM (100 mg/kg) coadministration group (about 77% increase), was
      comparable to that for the CYA alone group. Both CAM and EM (10 and 100 mg/kg,
      p.o.) were shown to delay gastric emptying in a dose-dependent manner. The
      gastric emptying in the group treated with CAM (100 mg/kg) was significantly
      lower than that with EM (100 mg/kg). It is suggested that CAM as well as EM might
      affect the oral bioavailability of CYA by inhibiting its metabolism and
      simultaneously by changing the gastrointestinal motility in rats. Thus, caution
      is recommended when administering CYA concomitantly with CAM to humans.

PMID- 8741586
TI  - Effect of pulse on iontophoretic delivery of desmopressin acetate in rats.
AB  - The effect of pulse parameters (duty and frequency) in a constant direct current
      iontophoresis on the antidiuretic response (elevation in rat urinary osmotic
      pressure) of desmopressin acetate (DDAVP) was examined in diabetes insipidus
      rats. Although antidiuretic response was not affected by frequency, it was
      induced by a duty of more than 26% and prolonged with increasing duty. A
      positively relationship between dose and AUC, the area under the osmotic pressure
      time curve, was confirmed by intravenous administration of DDAVP, and the AUC
      induced by the iontophoretic delivery increased with increasing duty. The voltage
      across rat skin required to maintain a constant current density was investigated.
      A higher voltage was initially applied rat skin in a higher duty. This was
      related the prolonged pharmacological response induced by iontophoresis.

PMID- 8741587
TI  - Enhancement of oral bioavailability and pharmacological effect of 1-(3,4
      dimethoxyphenyl)-2,3-bis(methoxycarbonyl)-4-hydroxy-6,7,8- trimethoxynaphthalene
      (TA-7552), a new hypocholesterolemic agent, by micronization in co-ground mixture
      with D-mannitol.
AB  - To improve the bioavailability of the sparingly water-soluble drug, 1-(3,4
      dimethoxyphenyl)-2,3-bis(methoxycarbonyl)-4-hydroxy-6,7,8- trimethoxynaphthalene
      (TA-7552), the usefulness of the co-grinding method with D-mannitol was
      investigated. The co-grinding was performed at various weight ratios of TA-7552
      and D-mannitol using a ball mill. The particle size was markedly reduced with
      increasing amount of D-mannitol. A mixture ratio greater than or equal to 1:3 of
      the drug and D-mannitol produced submicron-sized particles. In dogs,
      bioavailability increased with increasing amount of D-mannitol. The 1:9 co-ground
      mixture gave complete absorption, as did a lecithin solution of the drug. Even co
      ground powders with lower amounts of D-mannitol provided relatively high
      bioavailability in comparison with ground drug powder alone of a similar particle
      size. Further, pharmacological examination using rats indicated that the
      inhibition of cholesterol absorption was intestified with the reduction of
      particle size. These findings suggest that the co-grinding method with D-mannitol
      is useful for enhancing the bioavailability and pharmacological effectiveness of
      this sparingly water-soluble drug.

PMID- 8741588
TI  - Biosynthesis of the acetylenic compounds in cultured cells of Asparagus
      officinalis from D- and 13C-labelled phenylalanines.
AB  - Studies on the biosynthetic pathway of acetylenic compounds, 4-[5-(4
      methoxyphenoxy)-3-penten-1-ynyl]phenol and its related compounds, in cultured
      cells of Asparagus officinalis L. (Liliaceae) revealed that all of the 17 carbon
      atoms in their skeletons are supplied by phenylalanine. It is also concluded that
      p-substituted phenylacetylenic moieties (the C6-C2 unit) in these compounds are
      derived from C6-C3 shikimate pathway metabolites via phenylalanine. As a working
      hypothesis concerning the C6-O-C3 unit formation, a spirotetrahydrofuran type
      intermediate is predicted.

PMID- 8741589
TI  - Cell-density-dependent expression of the beta-adrenergic response by epidermal
      growth factor (EGF) in primary cultures of adult rat hepatocytes.
AB  - The effects of epidermal growth factor (EGF) and cell density on the appearance
      of beta-adrenergic responses were examined in primary cultures of adult rat
      hepatocytes. The beta-adrenergic response was measured as the ability to
      accumulate cAMP by beta 2-agonist metaproterenol in monolayers that had been
      cultured without or with 20 ng/ml EGF. Hepatocytes cultured with EGF at a high
      cell density (1.0 x 10(5) cells/cm2) showed a relatively lower response to 10
      microM metaproterenol. In contrast, when cultured at a low cell density (3.3 x
      10(4) cells/cm2) with EGF, the cells showed a higher response to the beta
      adrenergic agonist. These responses were blocked by the beta-adrenergic
      antagonist propranolol (10 microM). The beta-adrenergic response increased
      rapidly with culture time. The addition of cycloheximide (5 microM) to the
      culture abolished the expression of beta-adrenergic response. The enhanced beta
      adrenergic response by 20 ng/ml EGF was partially inhibited by the addition of
      cytochalasin B (20 microM) to the culture. The cAMP-producing response to
      metaproterenol (10 microM) was dose-dependently inhibited by the specific x2
      agonist UK-14304. Pretreatment of the hepatocytes with pertussis toxin (100
      ng/ml) potentiated the beta-adrenergic response. These results demonstrate that
      augmented beta-adrenergic responsiveness can be acquired by adult rat hepatocytes
      cultured with 20 ng/ml EGF at a low cell density, and the beta-adrenergic
      response involves de novo synthesis of protein(s). The results also show that
      significant alpha 2- and beta-adrenergic responses coexist in the primary
      cultures of adult rat hepatocytes.

PMID- 8741590
TI  - Effects of liposome size on penetration of dl-tocopherol acetate into skin.
AB  - Liposomes were prepared from hydrogenated lecithin (H-PC) by sonication (S) or
      injection (I) of H-PC dissolved in ethanol containing dl-tocopherol acetate
      (VEA). The effects of liposomes on the dermal absorption of VEA were studied. The
      particle diameter of S-liposomes was smaller than that of I-liposomes. The
      penetration of liposomal H-PC into the skin was much higher for S-liposomes than
      for I-liposomes 30 min after application to the arms of healthy human volunteers
      and also to hairless rat back skin. The penetration of 14C-VEA into hairless rat
      back skin was higher from the liposomes than from free VEA, and the 14C-VEA
      penetration was higher from S-liposomes than from I-liposomes. 3H
      Dipalmitoylphosphatidylcholine and 14C-VEA, which had been entrapped in
      liposomes, were not detected in plasma. H-PC inhibited the peroxidation of skin
      lipids. H-PC enhanced the penetration of VEA into the skin, but the degree of
      enhancement depended on the size of the liposomes, indicating that this liposomal
      characteristic was an important factor in dermal absorption and/or penetration.

PMID- 8741591
TI  - Assay for tryptophan hydroxylase activity in rat brain by high-performance liquid
      chromatography with fluorescence detection.
AB  - A highly sensitive and selective liquid chromatographic (HPLC) method with post
      column fluorescence detection has been developed for the determination of
      tryptophan 5-monooxygenase activity in rat brain tissue homogenate. 5
      Hydroxytryptophan, formed enzymatically from tryptophan (incubation time, 20
      min), is extracted with perchloric acid and determined by HPLC. Detection is
      performed fluorometrically after post-column derivatization by a reaction with
      benzylamine in the presence of potassium hexacyanoferrate (III). The lower limit
      of detection for 5-hydroxytryptophan formed enzymatically is 100 fmol at a signal
      to-noise ratio of three.

PMID- 8741592
TI  - Differences in the induction of carboxylesterase RL4 in rat liver microsomes by
      various perfluorinated fatty acids, metabolically inert derivatives of fatty
      acids.
AB  - Differences in the ability of metabolically inert peroxisome proliferators
      [perfluoro-n-decanoic acid (PFDA, C10), perfluoro-n-octanoic acid (PFOA, C8),
      perflorooctane sulfonic acid (PFOS, C8) and 1H,1H-pentadecafluoro-n-octanol
      (PFOL, C8)] to induce liver microsomal carboxylesterase RL4 in male rats were
      studied by evaluating changes in the RL4 content by immunoblot analysis with a
      specific antibody. The administration of PFOA, PFOS and PFOL markedly increase
      the content of carboxylesterase RL4. On the other hand, PFDA decreases PNPA,
      BUTA, and ISOC hydrolase activity, and slightly increases the carboxylesterase
      RL4 content.

PMID- 8741593
TI  - Hydrolytic cleavage of pyroglutamyl-peptide bond. II. Effects of amino acid
      residue neighboring the pGlu moiety.
AB  - We studied the susceptibility of the pyrrolidone moiety and the pyroglutamyl
      peptide bond at pGlu-X-Ala-Phe-OH (X = Gly, Ala, Tyr, Ile, Pro, His, Lys, Arg,
      Thr, Ser, Asp, Glu and Trp) to 1 N HCl or 2 M trifluoromethanesulfonic acid at 60
      degrees C. Here we describe the rates of the cleavage reaction of the pGlu-X
      bond, the pyrrolidone ring-opening reaction of the pGlu moiety and the
      hydrolysate accumulation. The rank order of the susceptibility rates of the
      cleavage reactions was Ser > Pro, Gly > Arg, Ala, Glu, Thr, Asp > His, Lys > Trp,
      Tyr, Ile, and that of the ring-opening reaction was Ile > Tyr, Trp > Arg, His,
      Lys, Asp > Glu > Ala > Pro, Gly > Ser > Thr. The rank order of the half-lives of
      the model peptides was Pro > Arg, Lys, Ile > His, Glu > Ala, Tyr > Asp > Gly >
      Ser > Thr. The results indicated that a bulky and sterically hindered side chain
      of the amino acid residue neighboring the pGlu moiety favors the ring-opening
      reaction, and retards the decomposition on acid hydrolysis and the cleavage
      reaction. Thus, the ring-opening and the cleavage reactions were greatly affected
      by the amino acid residue neighboring the pGlu moiety in the hydrolysis of pGlu
      peptides.

PMID- 8741594
TI  - Effect of polycarbophil on the absorption of nutrients.
AB  - The effects of polycarbophil on the absorption of various nutrients were
      evaluated by several in situ methods. Polycarbophil reduced the absorption of 3-O
      methyl-D-glucose (3-OMG) and L-phenylalanine in the in situ loop and the in situ
      perfusion methods, but it did not affect the absorption of these nutrients in an
      open system, the in situ modified loop method, which is closer to physiological
      conditions. It also did not affect the absorption of vitamin A or
      phosphatidylcholine-L-alpha-dipalmitoyl in the latter system. These results
      indicate that the absorption of nutrients is probably not altered by
      polycarbophil under physiological conditions.

PMID- 8741595
TI  - Synthesis of transferrin-mitomycin C conjugate as a receptor-mediated drug
      targeting system.
AB  - Macromolecular conjugates of mitomycin C (MMC) were synthesized by binding an
      active ester of glutarylated MMC (MMC-G-OSu) to human holo-transferrin (TF).
      Water-soluble TF-MMC conjugates (TF-G-MMC) were obtained in a good yield (> 95%)
      by this method. The MMC content of the conjugate increased (0.82-9.49 MMC/w%)
      with increasing amounts of MMC-G-OSu added to the conjugation mixture. Sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed no
      aggregation in these conjugates. 125I-TF-G-MMC was bound specifically to the TF
      receptor on Sarcoma 180 cells; the measurement of equilibrium binding of the 125I
      labeled conjugate resulted in a saturation isotherm. The amount of conjugate
      specifically bound to the TF receptor decreased as the MMC content of the
      conjugate increased. However, it was found that the conjugate with an MMC content
      below 10 mol MMC/mol TF still retains a binding activity of more than half that
      of TF. Therefore, when an optimal chemical modification was chosen, TF could be
      used as a tumor specific drug carrier.

PMID- 8741596
TI  - Contrast-enhanced MRI with gadodiamide injection in rabbit carcinoma models.
AB  - This study was designed to demonstrate the broad utility of contrast-enhanced
      magnetic resonance imaging (MRI) for diagnosis of carcinoma. Twenty-six New
      Zealand White rabbits of either sex (1.7-3.4 kg) were used for the investigation.
      VX2 carcinoma (squamous cell carcinoma) was implanted in either the brain, lung,
      ovary, bone or muscle of rabbits. Contrast agent, Gadodiamide Injection, was
      administered intravenously at a dose of 0.1 mmol/kg. MR images were obtained by a
      1.5 T, or a 2.0 T magnetic field strength super-conductive MRI unit. The
      intensity of the signal for the carcinoma was increased after administration of
      contrast agent, and the detectability or diagnostic information of post-contrast
      images was superior to that of pre-contrast images in all models. In addition, no
      significant side effects were observed during the MRI examination. After
      diagnosis using MRI, morphological damage in each model was assessed by gross and
      histopathological examinations. In contrast-enhanced MRI, though there were
      variations between the models employed, contrast effects in brain and muscle
      carcinoma models were generally related to differences in capillary permeability,
      while imaging in lung, ovary and bone carcinoma models was dependent on
      differences in blood flow rate and the size of interstitial spaces. Overall, our
      results demonstrate that contrast-enhanced MRI is a useful and safe method for
      diagnosing tumors.

PMID- 8741597
TI  - The effect of reflex closure of the esophageal groove on bioavailability of oral
      sulfamethoxazole-trimethoprim in ruminating calves.
AB  - The effect of reflex closure of the esophageal groove induced by the accustomed
      milking procedure on absorption of sulfamethoxazole (SMX)-trimethoprim (TMP)
      combination was examined, using calves trained to suck through a nipple-bucket.
      The experiment was carried out with a two-way cross-over design in which 2 groups
      of 5 calves of 6 weeks old were used. SMX-TMP combination was administered to the
      calves in each group through a nipple-bucket or an esophageal catheter. Tmax of
      SMX after nipple-bucket dosing was about 40 min shorter than that after catheter
      dosing. Cmax and AUC of SMX after the nipple-bucket dosing were 7.5 times greater
      and 6.9 times larger than those after the catheter dosing, respectively. Plasma
      TMP concentration was measurable only after the nipple-bucket dosing. These
      results suggest that a large portion of the drugs administered by the nipple
      bucket dosing, which induces closure of the esophageal groove, were transferred
      directly into the abomasum resulting in higher bioavailabilities of the drugs.

PMID- 8741598
TI  - Electrophoretic study of lactate dehydrogenase and alkaline phosphatase
      isoenzymes of the Mongolian gerbil (Meriones unguiculatus).
AB  - Lactate dehydrogenase and alkaline phosphatase isoenzymes of the Mongolian gerbil
      were examined using electrophoretic techniques and were compared with those of
      the mouse, rat, and guinea pig. Five isoenzymes of lactate dehydrogenase (LDH)
      were detected in the gerbil with LDH2 and LDH5 being equally dominant. Two bands
      of alkaline phosphatase (ALP) were distinguished in sera treated with
      neuraminidase in the gerbil and the relative activity of the cathodic fraction
      was greater than those of the mouse and rat. Genetic polymorphism was not found
      among the coat color variants of the Mongolian gerbil. A comparative study on LDH
      and ALP revealed distinct interspecific differences in the rate of the
      electrophoretic migration of the respective isoenzymes among the mouse, rat,
      guinea pig, and the Mongolian gerbil.

PMID- 8741599
TI  - Changes in bone metabolism and epiphysial growth plate in bovine Hyena disease
      induced by administration of vitamin AD3E premix or Vitamin A.
AB  - The changes in bone metabolism and morphology of chondrocytes in bovine Hyena
      disease caused by administration of vitamin AD3E premix (V-AD3E) or vitamin A (V
      A) were examined. At the each age, 5 calves were used. Among them, Hyena disease
      was recognized in 3 calves; a calf administered a high dose of V-AD3E premix (V-A
      3,000,000, V-D3 300,000, and V-E 1,200 I.U./day), a calf administered a half dose
      of the V-AD3E premix, and a calf administered only V-A 3,000,000 I.U./day. The
      remaining calves without Hyena disease were a calf administered only V-D3 300,000
      I.U./day and a control calf. Each agent was administered orally for 10 days from
      1 week after birth. In the 3 calves with Hyena disease, the bone metabolism in
      bone histomorphometry of ilium was in the state of low turnover at the age of 50
      days. The bone volume was small at the age of 12 months. The epiphysial growth
      plates of the distal femurs and the proximal tibias partially disappeared and the
      chondrocyte lacunas in them were flattened. The matrix fibers of epiphysial
      growth plates were thinner in diameter and higher in density than those of the
      control calf. In the calf administered only V-D3, the values of bone volume
      decreased with aging. In conclusion, Hyena disease may be caused by excessive
      administration of V-A, because hypervitaminosis A suppressed the activity of
      differentiation and proliferation in chondrocytes and osteoblasts, and excessive
      administration of V-D3 may promote these actions.

PMID- 8741600
TI  - Effects of maternal uninephrectomy on the development of the proximal tubule in
      fetal rat kidney: morphometrical study.
AB  - The kidneys of fetal rats from uninephrectomized mothers were investigated
      morphometrically on days 18, 20, and 22 of gestation. Maternal uninephrectomy was
      performed on day 5. On days 20 and 22, the proximal tubular cell height in
      fetuses from uninephrectomized mothers was significantly lower than that in
      fetuses from sham-operated mothers. The luminal diameter, length and total volume
      of the proximal tubule were significantly larger in fetuses from
      uninephrectomized mothers than in those from sham-operated mothers. The total
      glomerular volume of mature type in fetuses from uninephrectomized mothers was
      significantly larger than that in fetuses from sham-operated mothers. On day 18,
      maternal uninephrectomy caused no significant difference in any kind of
      parameters used for the proximal tubule, but induced an increase in the total
      glomerular volume of immature type. These results suggest that maternal
      uninephrectomy stimulates morphological development of the proximal tubule in the
      fetal kidney.

PMID- 8741601
TI  - Effect of M-711 on experimental skin reactions induced by chemical mediators in
      rats.
AB  - We investigated the mechanism of anti-allergic action of Moku-boi-to (M-711) and
      effects on the skin reactions induced by chemical mediators as the model of
      allergic dermatitis. More than 20 mg/kg BW of M-711 significantly suppressed the
      enhancement of capillary permeability induced by histamine, LTC4, and anti-serum
      in the rat skin. Anti-histaminic effect of 40 mg/kg BW of M-711 was equipotent to
      same as the optimal doses of azelastine and diphenhydramine, respectively. As to
      anti-LTC4 action, 20 mg of M-711 was compared to the optimal dose of
      diphenhydramine. Those data showed that M-711 has the suppressive effects on the
      chemical mediators such as histamine and LTC4 and reduced the skin reaction
      induced by antigen-antibody response.

PMID- 8741602
TI  - Antimicrobial effects of amikacin therapy on experimentally induced Salmonella
      typhimurium infection in fowls.
AB  - The antimicrobial effects of amikacin on Salmonella Typhimurium were investigated
      in fowls using pharmacokinetic parameters of amikacin and the minimum inhibitory
      concentration (MIC) of the drug for the bacteria. Pharmacokinetic parameters of
      amikacin after the intramuscular administration into the fowls were measured
      using the fluorescence polarization immunoassay. As there was no protein binding
      amikacin, the total concentration was identical to the free concentration. After
      inoculation of the bacteria, the following intramuscular dosage regimens were
      carried out to test the antimicrobial effects: injection with 20 mg/kg of
      amikacin sulfate every 9 hr for 72 hr, injection with 20 mg/kg every 18 hr for 72
      hr, injection with 20 mg/kg every 36 hr for 72 hr, and injection with 10 mg/kg
      every 12 hr for 72 hr. The control birds were not injected with amikacin.
      Abdominal organs were collected from each bird after the treatment ended. The
      organs were cultured and the number of colonies on each plate was calculated. No
      significant differences were detected among the four amikacin-treated groups,
      whereas the number of colonies in the control group was significantly higher than
      that in the amikacin-treated groups. An antimicrobial drug concentration
      exceeding the bacterium's MIC for at least 1/4 of the administration interval
      might be effective for the treatment of the infection, and the degree of peak
      drug concentration had no effect on antibacterial activity as long as the
      duration of the drug concentration above the MIC value remained the same.

PMID- 8741603
TI  - Characterization of T cells expanded in vivo during primary mouse hepatitis virus
      infection in mice.
AB  - After intraperitoneal infection with mouse hepatitis virus, strain JHM (JHMV),
      JHMV replicated in the spleen of C57BL/6 mice for a few days but cleared within a
      week. The acute viral clearance coincided with moderate expansion of CD8+T cells
      and modest expansion of CD4+T cells, and was impaired moderately in mice depleted
      of CD8+T cells and completely in mice depleted of both CD4+ and CD8+T cell
      subsets. Flow cytometric analysis showed that expression of cell surface markers
      on the spleen T cells changed during JHMV infection. CD8+T cells expressing
      increased amounts of CD11a, CD43, CD44 and CD49d, and those expressing decreased
      levels of T cell receptor alpha beta, CD8, CD45RB and L-selectin were expanded in
      the spleen after JHMV infection. However, they did not express CD11b, CD25 or
      NK1.1. They used highly heterogenous V beta chains for their T cell receptors. In
      addition to CD11ahighCD8+T cells, CD11ahighCD4+T cells were detected transiently
      after JHMV infection. The virus-specific cytotoxic T lymphocyte (CTL) activity
      was observed in both CD4+ and CD8+ spleen T cells from mice 7 days post
      infection. The present study shows the dynamics of CD8+ and CD4+T cells in the
      spleen during JHMV infection in mice and suggests that CD11ahighT cells may be
      involved in JHMV clearance in vivo because their appearance was temporally
      correlated with T cell-mediated viral clearance in vivo and antiviral CTL
      activity in vitro.

PMID- 8741604
TI  - Biological properties and antibiotic susceptibility of Bacillus larvae originated
      from American foulbrood of honeybee in Japan.
AB  - The biological properties and susceptibility to antimicrobial agents of Bacillus
      larvae were examined. Twenty-nine strains, 28 isolates from each outbreak of
      American foulbrood in Japan and a B. larvae type strain (ATCC 9545T) were used.
      our B. larvae isolates had almost the same biological properties as the type
      strain. The isolates were more susceptible to penicillins, macrolides and
      lincomycin, a lincosamide, than other antimicrobials. Microsamicin among the
      macrolides and ampicillin among the penicillins appeared to be the most effective
      agents.

PMID- 8741605
TI  - Observation of the growth process of a beagle embryo and fetus by
      ultrasonography.
AB  - Detailed observations of the growth process of the embryos and fetuses
      (hereafter, referred to as just fetus) of 6 pregnant Beagle bitches (14-27 months
      old) was carried out using ultrasonography. From daily measurements of the
      transversal diameter of the fetal abdomen, diameter of the fetal head and
      diameter of the fetal heart, significant growth curves (secondary regression
      equations) were obtained from the day of gestation and the measured values (p <
      0.01). The results of this study showed that this method can be applied to
      estimate the gestation age of dogs in cases when the mating day is unknown, and
      determine the state of fetal growth.

PMID- 8741606
TI  - Alveolar hydatidosis in a gorilla and a ring-tailed lemur in Japan.
AB  - Alveolar hydatidosis by Echinococcus multilocularis (Em) infection occurred on a
      22-year-old (approx.) male gorilla (Gorilla gorilla) and a 4-year-old female ring
      tailed lemur (Lemur catta) in a zoo, in Hokkaido, Japan. Case 1: The gorilla
      presented neurologic signs in course of nine months and died. Pathologically,
      alveolar hydatid lesions were found in the liver, the liver-associated lymph
      nodes, the cerebrum, and the lungs. A protoscolex was found only in one hepatic
      cyst. Case 2: In the lemur, large masses of hydatide cysts were found on the
      liver and at the lung-associated lymph nodes. Cysts contained numerous calcareous
      corpuscles and protoscolices. The lemur appears a favorable intermediate-host for
      Em. The identification of Em in both cases were confirmed by PCR.

PMID- 8741607
TI  - Multifocal ventricular tachycardia after resuscitation by direct current counter
      shock in a dog.
AB  - Cardiac arrest occurred in a male Labrador Retriever dog weighing 27.8 kg during
      induction to anesthesia. Immediately after the failure of resuscitation by the
      external cardiac compression, thoracotomy was performed and open chest direct
      current (DC) counter shocks were applied with routine emergency medications. Then
      the dog recovered consciousness. Although cardiac rhythm just after resuscitation
      was sinus tachycardia with paroxysmal supraventricular tachycardia, multifocal
      ventricular arrhythmia occurred 2 hr after resuscitation. This arrhythmia might
      be the result from reversible cardiac lesions due to DC counter shock.

PMID- 8741608
TI  - Detection of antibodies against bovine immunodeficiency-like virus in daily
      cattle in Hokkaido.
AB  - Serological survey of bovine immunodeficiency-like virus (BIV) infection was
      performed in cattle of 3 different farms in Hokkaido, where a relatively high
      seroprevalence was recorded for bovine leukemia virus (BLV). About a half of 120
      cattle tested were seropositive for BLV, while 7.5% of the cattle were
      seropositive for BIV. Though increased numbers of leukocytes were frequently
      observed in BLV-seropositive cows, no such changes were observed in BIV-positive
      but BLV-negative cows. No correlation was demonstrated between BIV- and BLV
      seroprevalence of the cattle.

PMID- 8741609
TI  - Demonstration of infectious bovine rhinotracheitis virus antigen by
      immunoperoxidase method in tissues of aborted bovine fetuses preserved for 25
      years in paraffin blocks.
AB  - Infectious bovine rhinotracheitis (IBR) virus antigen was demonstrated by the
      immunoperoxidase method in tissues of two aborted bovine fetuses, which had been
      stored for 25 years after fixing in formalin and embedding in paraffin. Necrotic
      foci were detected in the liver, kidney, adrenal gland, and thymus of the
      fetuses. Coincidenting with the distribution of the necrotic foci, IBR virus
      antigen was demonstrated by immunostaining. The present study proved the
      immunoperoxidase method in one of useful techniques to demonstrate IBR virus
      antigen in tissue sections from preserved paraffin blocks.

PMID- 8741610
TI  - Serum vitamin A and vitamin E in Japanese black fattening cattle in Miyazaki
      prefecture as determined by automatic column-switching high performance liquid
      chromatography.
AB  - Japanese Black fattening cattle in Miyazaki prefecture, Japan were examined for
      serum vitamin A (V. A) and vitamin E (V. E) by automatic column-switching high
      performance liquid chromatography with automated deproteinization. Results
      indicated that most Japanese Black fattening cattle in Miyazaki prefecture may be
      provided with V. A supplement and diets including little V. E, moderate beta
      carotene and V. A during the early fattening stage, and diets including little
      beta-carotene, V. A and V. E during the middle and later fattening stages.
      Therefore, monitoring serum V. A and V. E in Japanese Black fattening cattle
      throughout the fattening period seems necessary for farmers in Miyazaki
      prefecture to avoid economic loss attributable to these deficiencies.

PMID- 8741611
TI  - Generation of antiviral CD11ahigh T cells in CD4+ T cell-depleted mice and adult
      thymectomized mice after mouse hepatitis virus infection.
AB  - The mechanism of CD11ahighCD8+ T cell induction after mouse hepatitis virus
      infection, which has been suggested to play a key role in the elimination of
      infectious virus from the spleen in C57BL/6 mice, was studied. In CD4+ T cell
      depleted mice, CD11ahighCD8+ T cells were induced in the spleen and spleen cells
      showed virus-specific cytotoxic T lymphocyte activity after mouse hepatitis virus
      infection. The same results were obtained in adult thymectomized mice. These
      results indicate that CD11ahighCD8+ T cells can be generated after mouse
      hepatitis virus infection in the absence of either CD4+ T cells or the thymus.

PMID- 8741612
TI  - Establishment and characterization of a new canine B-cell leukemia cell line.
AB  - A new cell line derived from a spontaneous canine leukemia was established and
      designated GL-1. The cells have been cultured in a floating fashion and passaged
      for over two years. They were round with rich cytoplasm containing many rough
      endoplasmic reticula and mitochondria. Peroxidase staining was negative. The
      nuclei of many cells were round, but segmented nuclei were seen frequently. The
      doubling time of the cells was 27.3 hr and they had 78 chromosomes. Surface
      marker analysis using monoclonal antibodies (MABs) and flowcytometry revealed
      that GL-1 possessed CD45 and surface IgG. However, the cells did not react with
      MABs detecting T-cell markers. These results indicate that GL-1 has a lymphocytic
      lineage and is derived from a B-cell leukemia.

PMID- 8741613
TI  - Canine infectious cyclic thrombocytopenia found in Taiwan.
AB  - Here were report the first canine infectious cyclic thrombocytopenia (CICT) found
      in Taiwan. Platelet-specific inclusions were detected in the blood smear of a
      military working dog. To identify the etiologic agent, the patient's blood was
      transmitted to three six-month-old German Shepherd dogs. The Ehrlichia platys
      like inclusions were observed six to eight days after inoculation. Indirect
      fluorescent antibody test showed that the serum from the patient reacted
      specifically with the microorganisms within the platelets. Typical hematologic
      manifestations of E. platys infection, cyclic parasitemia and concomitant
      thrombocytopenia, were observed in these dogs. The prevalence of CICT in north
      Taiwan was also studied, and the incidence was 8.9% (4 out of 45) in civilian
      dogs and 97.1% (34 out of 35) in dogs from a heavily tick infested kennel.

PMID- 8741614
TI  - A simple preparation of mycoplasmal DNA template for PCR from biological samples
      using effective surfactants.
AB  - To prepare mycoplasmal DNA template for PCR from biological samples rapidly and
      easily, surfactants which can solubilize cell membranes effectively were
      investigated. 3-[3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS)
      was considered an effective surfactant. This surfactant could solubilize
      mycoplasma cell membrane without suppressing the polymerase reaction. In
      addition, proteinase K treatment played an important role in preparing
      mycoplasmal DNA template from a simulated biological sample. It was therefore
      considered that a combination of proteinase K- and CHAPS- added lysis buffer
      would be more useful in preparing mycoplasmal DNA template. We could detect PCR
      products by using the lysis buffer with a simulated lung emulsion sample
      containing mycoplasma organisms at 10(4) CFU per gram.

PMID- 8741615
TI  - Classification of the cycle of the seminiferous epithelium in the common tree
      shrew (Tupaia glis).
AB  - The classification of the cycle of the seminiferous epithelium was carried out in
      the common tree shrew (Tupaia glis). The tree shrew captured in Thailand were
      fixed with Bouin's fixative, embedded in paraffin wax, and stained with PAS
      hematoxylin. The cycle was classified into twelve stages on the basis of the
      acrosomal changes of spermatids. Relative frequencies of stages form I to XII
      were 11.9, 7.2, 8.9, 22.5, 12.9, 9.7, 8.0, 5.9, 4.0, 3.2, 2.9, and 3.6%,
      respectively. Different stages did no appear in a cross-sectioned tubule as did
      in primates. The head of matured spermatid was discoidal in shape and different
      from that of primates and rodents. Spermatogenesis of the common tree shrew is
      different from that of primates and rodents according to its morphological
      features.

PMID- 8741616
TI  - A one-dimensional current source-density analysis is applicable to the mouse
      accessory olfactory bulb.
AB  - Field potentials evoked in the accessory olfactory bulb (AOB) of the mouse by a
      vomeronasal organ (VNO) volley were analyzed with current source-density (CSD)
      techniques. The potentials were recorded with an electrode oriented in the
      direction perpendicular to the laminae of the centre of the AOB in five tracks of
      equal spatial lattice for identical coordinates. There were little or no
      differences in the amplitude or time course of the potentials at equal depth
      among the five tracks. The CSD profile from a one-dimensional CSD analysis
      corresponded closely with that of a three-dimensional CSD analysis of a central
      track in the AOB. Furthermore, VNO-evoked field potentials were recorded in the
      AOB external plexiform layer while an electrode was being moved in the direction
      parallel to this layer. The potentials recorded at adjacent points were nearly
      identical and hence the related one-dimensional CSD calculations revealed no net
      currents along this layer. These results indicate that a one-dimensional CSD
      analysis is applicable to the mouse AOB.

PMID- 8741617
TI  - [Mechanisms of eukaryotic transcription initiation and its regulation centered on
      general transcription factors].

PMID- 8741618
TI  - [Helix-loop-helix transcription factor network regulating mammalian
      neurogenesis].

PMID- 8741619
TI  - [Function of the PEBP2/CBF/AML1 genes].

PMID- 8741620
TI  - [Gene network regulating muscle development].

PMID- 8741621
TI  - [Gene program regulating differentiation of embryonal carcinoma cells].

PMID- 8741622
TI  - [Transcriptional regulation of DNA replication-related genes during Drosophila
      melanogaster development].

PMID- 8741623
TI  - [Ad4BP/SF-1 and sex differentiation of the gonads].

PMID- 8741624
TI  - [Regulation mechanism of specific transcription in erythroid differentiation].

PMID- 8741625
TI  - [Involvement of maf gene family in crystallin gene regulation].

PMID- 8741626
TI  - [Pax-5, a transcription factor controlling B cell differentiation].

PMID- 8741627
TI  - [Is retinoic acid essential for the development?].

PMID- 8741628
TI  - [Downstream of Hox genes].

PMID- 8741629
TI  - [Developmental expression patterns and target assignment of the bombyx fork head
      and POU-M1 genes].

PMID- 8741630
TI  - [Transcriptional regulation by Hox gene products].

PMID- 8741631
TI  - [Drosophila imaginal development and the escargot gene].

PMID- 8741632
TI  - [The engrailed gene and the compartment hypothesis].

PMID- 8741633
TI  - [Involvement of SOX proteins in activation of crystallin genes and lens
      development].

PMID- 8741634
TI  - [The structure and function of general transcription factor TFIIA].

PMID- 8741635
TI  - [Multistep transcriptional regulation by the general transcription factor TFIIE
      and TFIIH].

PMID- 8741636
TI  - [Analysis of the mechanism of transcriptional regulation based on yeast system].

PMID- 8741637
TI  - [Regulation of general transcription factors by phosphorylation].

PMID- 8741638
TI  - [Detection of TBP-interacting proteins (TIPs) and demonstration of a novel
      complex containing TBP and ATPases].

PMID- 8741639
TI  - [Interaction between yeast transcription factor GAL11 and general transcription
      factors].

PMID- 8741640
TI  - [Role of yeast global repressors, Bel2 and Tup1, in chromatin-and nucleosome
      mediated transcriptional regulation].

PMID- 8741641
TI  - [NF-kappa B system].

PMID- 8741642
TI  - [Transcription regulation by FTZ-F1].

PMID- 8741643
TI  - [Molecular analysis of MIDA1, which associates with Id1].

PMID- 8741644
TI  - [Transcription factors involved in histone gene regulation].

PMID- 8741645
TI  - [Transcription factors NF-IL6 and STAT3 involved in cytokine signal
      transductions].

PMID- 8741646
TI  - [Interaction of HTLV-1 Tax with cellular factors].

PMID- 8741647
TI  - [Signal transduction pathways mediated by small GTPases and protein kinases].

PMID- 8741648
TI  - [Signal transduction of steroids and vitamins mediated by nuclear receptor
      proteins].

PMID- 8741649
TI  - [The function of the transcription factor, IRF family, in the interferon system].

PMID- 8741650
TI  - [Cross-point of cAMP and Ca2+ signals to the transcription factors].

PMID- 8741651
TI  - [Structure and function of PAS proteins: Ah receptor, Arnt, and others].

PMID- 8741652
TI  - [Analysis of self-renewal mechanism of hematopoietic stem cells using transgenic
      mice expressing cytokine receptors].

PMID- 8741653
TI  - [Structure and DNA recognition of transcription factors].

PMID- 8741654
TI  - [Myb: structure and regulation of activity].

PMID- 8741655
TI  - [Molecular communications in transcription: basic mechanisms of transcription
      regulation].

PMID- 8741656
TI  - [Where transcriptional factor research in developmental biology should go].

PMID- 8741657
TI  - [Cancer and transcriptional regulation].

PMID- 8741658
TI  - [Apoptosis: concept, research history and clinical significance].

PMID- 8741659
TI  - [Molecular biology of Fas antigen-Fas ligand system].
AB  - Fas antigen is a type I membrane protein of 45 kDa that belongs to the tumor
      necrosis factor (TNF)/nerve growth factor receptor family. The binding of
      agonistic anti-Fas antibody or Fas ligand to Fas antigen induces apoptosis. The
      unique motif "death domain" in the cytoplasmic region of Fas antigen is essential
      for the initiation of apoptosis. Fas ligand is a type II membrane protein of 40
      kDa that belongs to the TNF family. Fas ligand is predominantly expressed in
      activated T cells. Fas system plays an important role on the clonal deletion of
      autoreactive T cells and T cell-mediated cytotoxicity.

PMID- 8741660
TI  - [The molecular structure and biological significance of soluble Fas].
AB  - Fas (APO-1/CD95) is a type I membrane-bound protein belonging to the TNF receptor
      family. Fas mediates apoptosis by its crosslinking with Fas ligand or some
      monoclonal anti-Fas antibodies. As a number of cytokine receptors and cell
      surface antigens exist in soluble or secreted form, soluble Fas is present at low
      levels in the sera of healthy persons and at elevated levels in the sera of
      patients with autoimmune diseases and hematologic malignancies. In this
      minireview we summarize current knowledge of the molecular structure of soluble
      Fas translated from alternatively spliced Fas mRNA in humans and animals, and
      discuss the biological and clinical significance of soluble Fas.

PMID- 8741661
TI  - [Metalloproteinase-mediated release of human fas ligand].
AB  - Fas (APO-1, CD95) is a type I integral membrane protein initially identified by
      mAbs that induce apoptotic cell death upon binding to certain tumor cells and its
      belongs to the TNFR family. Fas is expressed on activated lymphocytes and in
      various tissues including the liver, lung, intestine, and skin. Molecular cloning
      of Fas ligand (FasL) revealed that it is a type II integral membrane protein
      homologous to TNF. FasL is predominantly expressed on activated T and NK cells,
      and mediates Fas divided by target cell lysis by these effector cells. The
      Fas/FasL system has been also implicated in the pathogenesis of autoimmune
      diseases, fulminant hepatitis, GVHD, and AIDS. It has been recently reported that
      human FasL was released as a 26 kD soluble form from COS cells transfected with
      human FasL cDNA and activated human T cells. In this communication,
      metalloproteinase-mediated release of FasL and it's clinical relevance are
      discussed.

PMID- 8741662
TI  - [Regulation of thymocyte apoptosis and positive selection].
AB  - Developing T cells undergo thymic selection at the CD4+CD8+ stage. Only less than
      5% of CD4+CD8+ thymocytes are positively selected to survive and differentiate
      into mature single positive CD4 or CD8 T cells. Positive selection requires
      signaling through the T cell receptors (TCR) with assistance of CD4 or CD8
      coreceptor and LFA-1, but its molecular mechanism is poorly understood. By using
      glucocorticoids, anti-apoptotic activity was detected in CD4+CD8+ thymocytes upon
      proper cross-linking of TCR/CD3 complex with CD4, CD8, or LFA-1, and was mimicked
      by a combination of a calcium ionophore and a protein kinase C activator.
      Isolated CD4+CD8+ thymocytes underwent differentiation and commitment to the CD4
      T cell lineage by moderate and transient stimulation with this combination of the
      drugs.

PMID- 8741663
TI  - [Programmed thymic T cell death and negative selection via Fas and TCR/CD3
      complex].
AB  - In the immune system of thymic microenvironment, immature T cells are selected by
      T cell receptor (TCR)-mediated antigen stimulation and most of thymic T cells die
      by apoptosis. Molecular mechanism for the elimination of autoreactive T cells by
      apoptotic cell death in thymus is almost unknown, though a differential avidity
      model for TCR-mediated selection is recently proposed. On the other hand, Fas
      antigen (Fas), which is apoptosis inducing cell surface receptor, is expressed on
      antigen stimulated human thymocytes and involved in superantigen-induced negative
      selection. Recent studies have suggested that CD30 and CD40 ligand (gp39) on
      thymocytes is also involved in a part of negative selection. Thus, it is likely
      that the process of negative selection may involve multiple, and to some extent
      redundant, costimulation signals.

PMID- 8741664
TI  - [NGFI-B/nur77 family involved in T-cell apoptosis].
AB  - NGFI-B/nur77 is a member of the steroid receptor superfamily. NGFI-B/nur77 and
      its related genes constitute a family and the NGFI-B/nur77 family consists of
      three subtypes, named nur77 alpha, nur77 beta, nur77 gamma. We cloned human nur77
      beta cDNA, called TINUR. Although NGFI-B/nur77 is essential for TCR-mediated
      apoptosis in T-cell hybridomas, the reports on nur77 knock-out mice and nur77
      dominant negative transgenic mice suggest that there is a functional redundancy
      among NGFI-B/nur77 family. NGFI-B/nur77 binds to the response element by monomer
      or heterodimer with retinoid X receptor (RXR). Assuming that 9-cis-retinoic acid
      (9-cis-RA) inhibits TCR-mediated apoptosis, nur77 may cause apoptosis by monomer
      in the absence of 9-cis-RA and may inhibit apoptosis by heterodimer with RXR in
      the presence of 9-cis-RA.

PMID- 8741665
TI  - [Function of HS1 protein in B-cell antigen-receptor signaling and induction of
      apoptosis].
AB  - Cross-linking of antigen receptor complex on the surface of B cells induces
      activation of the associated protein-tyrosine kinases (PTKs) which, in turn,
      phosphorylate and activate a variety of intracellular proteins, some of those are
      known to transmit the signal to further downstream. In some circumstances, such
      signals eventually result in apoptosis, rather than proliferation, of the cells.
      The programmed B-cell death is thought to be crucial in developmental selection
      of functional cells, self-tolerance, regulation of immune response, and so on.
      Molecular mechanisms of the intracellular signaling pathways leading to the
      apoptosis are still obscure. HS1, a hematopoietic-lineage specific protein, is a
      major substrate of the antigen-receptor associated PTKs. The biochemical and
      predicted structural features suggest HS1 actively involves in the signal
      transduction pathway from the antigen receptors and may directly regulate a gene
      transcription. In this review article, discussed are the roles of non-receptor
      type tyrosine kinases and HS1 in the pathway leading to apoptosis of B cells,
      recently evidenced by cell- and mouse-genetics.

PMID- 8741666
TI  - [Role of LFA-1/ICAM-1-dependent cell adhesion in CD40-mediated inhibition of anti
      IgM antibody-induced B-cell death].
AB  - To investigate the role of CD40-transduced signals in surface IgM (sIgM)-mediated
      B cell death, we used a human B cell line (DND-39). Crosslinking of sIgM by Abs
      induced DND-39 cell death (apoptosis). Anti-CD40 Abs induced homotypic adhesion
      of DND-39 cells and rescued them from anti-IgM Ab-induced apoptosis. Treatment
      with Abs against LFA-1/ICAM-1 inhibited not only the homotypic adhesion but also
      the inhibition of anti-IgM Ab-induced apoptosis by anti-CD40 Ab. Otherwise, CD11a
      antisense decreased the inhibitory effect of anti-CD40 Ab on anti-IgM Ab-induced
      apoptosis. The data show that LFA-1/ICAM-1-dependent cell adhesion induced by
      signaling through CD40 plays an important role in the inhibition of anti-IgM Ab
      induced apoptosis of DND-39 cells.

PMID- 8741667
TI  - [RP105 and B cell apoptosis].
AB  - The RP105 is a novel, murine B cell surface molecule that is expressed on mature
      B cells but not on pre-B or T cells. The RP105 is a 150 kDa type I transmembrane
      protein, and a member of the leucine-rich repeat protein family. Tandem repeats
      of a leucine-rich motif in the extracellular domain are thought to be involved in
      processes such as cell adhesion or receptor-ligand interactions. An antibody
      against RP105 protects B cells from irradiation- or dexamethasone-induced
      apoptosis, and drives them to proliferate. B cells activated by RP105-ligation
      arrest their growth and undergo apoptosis when the antigen receptor is engaged.
      Thus, RP105 is a signal transduction molecule and seems to have a role in
      regulation of B cell growth and death.

PMID- 8741668
TI  - [Fas antigen expression on human hematopoietic progenitor cells].
AB  - We investigated the expression of Fas(CD95) on hematopoietic progenitor cells.
      CD34+ cells freshly isolated from bone marrow did not express Fas. However,
      interferon-gamma(IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha)
      induced the expression of Fas after 48 hours of serum-free culture. The TNF-alpha
      induced Fas expression is mediated by p55-TNF-alpha receptor. Human CD34+ cells
      expressed Fas following low dose ionizing radiation in a dose-dependent fashion.
      CD34+ cells isolated from bone marrow were cultured with hematopoietic growth
      factors for 7 days. CD34+ cells cultured with hematopoietic growth factors
      gradually became positive for Fas and rapidly lost Bcl-2 expression. Fas system
      is considered to play important roles at the level of hematopoietic progenitor
      cells in both physiologic and pathologic conditions.

PMID- 8741669
TI  - [Cytokines regulate apoptosis of leukemic cells].
AB  - It is clear that cytokines regulate normal hematopoiesis including proliferation,
      differentiation, and apoptosis (programmed cell death). Leukemia is a disorder of
      unbalance between excessive proliferation and inappropriate apoptosis. Leukemic
      cells are also stimulated by cytokines similar to normal hematopoietic cells. It
      is reported that the oncogenes and tumor suppressor genes are associated with not
      only leukemogenesis but also cell cycle, for example proliferation,
      differentiation, and apoptosis (programmed cell death). We found that G-CSF leads
      to apoptosis of radiation induced murine leukemia cell line (C2M-A5), and its
      apoptosis is dependent on cell cycle. From these results together with other
      related reports, cytokines seem to be a key substance of apoptosis of leukemic
      cells and the apoptosis inducing therapy will be a new strategy for leukemia
      therapy.

PMID- 8741670
TI  - [Ceramide: a lipid mediator of apoptotic signal transduction].
AB  - Ceramide, the backbone of sphingolipids, is now recognized as an intracellular
      signal mediator of various cellular responses including cell differentiation and
      apoptosis. Tumor necrosis factor-alpha, anti-Fas antibody, anticancer drugs,
      radiation or heat shock induce apoptosis through generation of ceramide by
      activation of sphingomyelinase or ceramide synthase. The mechanism by which
      ceramide mediates apoptosis is unclear. We have found that ceramide induces the
      transcription of c-jun gene and increases the DNA binding activity of
      transcription factor AP-1 in human myelogenous leukemia HL-60 cells, and that
      activation of c-jun/AP-1 by ceramide(presumably through activation of Jun N
      terminal kinase/stress-activated protein kinase) may be involved in the signaling
      pathway leading to apoptosis.

PMID- 8741671
TI  - [Induction of apoptosis by fibronectin via its interaction with VLA5].
AB  - Little is known how Extra cellular matrix (ECM) molecules regulate proliferation
      of human hematopoietic progenitor cells. Fibronectin (FN) strikingly inhibited a
      human growth factor dependent cell line, M07E, cell proliferation. DNA content
      analysis revealed that FN treatment resulted in the appearance of subdiploid
      peak. Furthermore, FN induced oligonucleosomal DNA fragmentation and chromatin
      condensation, suggesting the involvement of apoptosis in the FN induced growth
      suppression. The apoptosis was rescued by anti-VLA5 mAb and the FN-induced
      apoptosis was detectable only VLA5-positive human cell lines but not in any of
      the VLA5-negative cell lines. These results suggest that FN induces apoptosis via
      its interaction with VLA5, and also raise the possibility that the FN-VLA5
      interaction may contribute to negative regulation of hematopoiesis.

PMID- 8741672
TI  - [Overexpression of bcl-2 suppresses apoptotic cell death of the human leukemic
      cell line TF-1].
AB  - We analyzed the effect of overexpression of bcl-2 gene on cell cycle progression,
      using the growth factor dependent cell line, TF-1, derived from an
      erythroleukemia patient. TF-1 (bcl-2) cells, which were transfected with bcl-2
      cDNA by the retrovirus vector system, survived and arrested in the G0-1 phase on
      GM-CSF removal. Centrifugal elutriation studies showed that G0-1-arrested
      subfraction of TF-1 (bcl-2) reentered the cell cycle with time delay upon GM-CSF
      re-addition, when compared with TF-1 (mock). A similar delay in cell cycle
      progression was observed during the recovery phase after 24h-exposure to
      staurosporine, a protein kinase C(PKC) inhibitor. These results imply functional
      involvement of bcl-2, both in the GM-CSF and the PKC signal transduction pathway
      and in G0-1 progression.

PMID- 8741673
TI  - [The mechanism of apoptosis induced by anticancer agents in human leukemia
      cells].
AB  - Many anticancer agents induce apoptosis in human leukemia cells. Among the
      various leukemia cells, especially HL-60 cells and U937 cells are very sensitive
      to apoptosis upon anticancer agents treatment. A serine protease inhibitor TPCK
      and an ICE-like protease inhibitor VAD-FMK prevented etoposide, camptothecin and
      ara-C-induced internucleosomal DNA cleavage in human myeloid leukemia HL-60 and
      U937 cells. Using a cell-free system, we have examined the inhibitory mechanism
      of these inhibitors on anticancer agent-induced internucleosomal DNA cleavage.
      Our data indicate that serine and ICE-like proteases may be involved in
      anticancer agent-induced apoptosis at the different stages, and especially a
      serine protease may be closely associated with the final step for induction of
      DNA fragmentation during apoptosis in human myeloid leukemia HL-60 and U937
      cells.

PMID- 8741674
TI  - [Degradation of topoisomerase II alpha precedes nuclei degeneration during
      adenovirus E1A-induced apoptosis and is mediated by the activation of the
      ubiquitin dependent proteolysis system].
AB  - Adenovirus type 2 E1A gene product induces nuclear degeneration and apoptosis of
      human epithermoid carcinoma cell line MA1 within 72 h after its expression.
      Western-blot analysis revealed that the level of topoisomerase II alpha begins to
      decrease posttranscriptionally within 36 h after E1A expression, preceding the
      onset of DNA fragmentation. The decrease of topoisomerase II alpha was suppressed
      in the MA1 derivative E1B19k or Bcl-2 expressing cell lines that refractory to
      E1A-induced apoptosis. Topoisomerase II alpha of the nuclear matrix or prepared
      by immunoprecipitation was degraded more efficiently in the S10 extract prepared
      from MA1 cells treated with DEX for 42 h than in the extract from untreated MA1
      cells in an ATP and ubiquitin dependent manner. These data suggest that
      degradation of topoisomerase II alpha is a key event that destines cells to
      apoptosis, and is catalyzed by the ubiquitin proteolysis pathway that is
      activated during the latent phase of E1A-induced apoptosis.

PMID- 8741675
TI  - [Mechanism of the induction of apoptosis by influenza virus infection].
AB  - Influenza virus frequently causes acute respiratory inflammation. We and others
      have observed that influenza virus infection induces apoptosis both in vitro and
      in vivo. We found that the virus infection induces augmented Fas expression. We
      proposed that double-stranded RNA (dsRNA) activated protein kinase (PKR) is
      involved in Fas expression since a synthetic dsRNA activated Fas gene and
      exposure of the cells to anti-interferon-beta antibody, which decreased the PKR
      activity, suppressed the cell death, as well as an increase in Fas mRNA.
      Furthermore, transfecting the mutant PKR suppressed the augmented Fas expression
      and rendered the cells resistant to death upon virus infection. These results
      suggest that Fas gene activation in virus-infected cells is regulated by the
      PKR/interferon system.

PMID- 8741676
TI  - [Apoptosis induction and its mechanism in HIV infection].
AB  - Evidence is accumulating that apoptotic pathways account for the depletion of CD4
      T cells in HIV-1 infected individuals. These pathways may be mediated, either
      directly by a virus infection or indirectly, through the priming of uninfected
      cells to apoptosis, when triggered by different agents. The participation of
      apoptosis in the cytopathic effect of CD4 T cells infected with HIV, in vitro,
      has already been shown. In our study using human CD4 cell clones expressing gp160
      of HIV-1 under the control of inducible promoter, cell killing due to apoptosis
      was induced in the cells when gp160 was synthesized and a complex formed with
      gp160 in the cell. Non-infected CD4 T cells present in the vicinity of an
      infected cell may be killed through several mechanisms that involve gp120-CD4
      interactions. Gp120 shed from infected cells can interact with CD4 on non
      infected cells. Cross-linking of CD4 by such gp120 or by further binding of anti
      gp120 antibody to gp120 may prime CD4 T cells for apoptosis following antigen
      driven activation.

PMID- 8741677
TI  - [Anti-apoptotic function of the Epstein-Barr virus LMP1 and BHRF1 proteins].
AB  - Two Epstein-Barr virus (EBV) gene products, latent infection membrane protein 1
      (LMP1), expressed mainly in latent infection, and BHRF1, expressed in lytic
      infection, have the ability to promote cell survival. LMP1 protects human B cells
      from apoptosis by upregulating expression of Bcl-2 and A20. We have demonstrated
      that LMP1 transfectants of Jurkat T cells are resistant to apoptosis induced by
      serum depletion without affecting the Bcl-2/Bax system. Overexpression of LMP1 in
      epithelial cells inhibits apoptosis induced by TNF-alpha, but not by anti-Fas
      antibodies. These results indicate that the anti-apoptotic mechanism of LMP1
      differs among different cell types. BHRF1 can prevent apoptosis induced by TNF
      alpha and anti-Fas antibodies in epithelial cells. The implication of the anti
      apoptotic function of LMP1 and BHRF1 is reviewed in relation to EBV infection.

PMID- 8741678
TI  - [The human T-cell leukemia virus type I (HTLV-I) tax protein induces apoptosis].
AB  - Human T-cell leukemia virus type I (HTLV-I) is an etiological agent of adult T
      cell leukemia. The Tax protein of HTLV-I may play a central role in cellular
      transformation. By serum deprivation, Tax-transformed Rat-1 cells undergo
      apoptotic cell death. These cells exhibit DNA fragmentation and chromatin
      condensation. Constitutive expression of bcl-2, blocked Tax-mediated apoptosis.
      Activation of fusion protein containing Tax and estrogen receptor, also led to
      the trans-activation and caused inhibition of proliferation and apoptosis.
      However Tax inhibited anti-Apo-1-induced apoptosis. Apoptosis appear to be the
      most important process of HTLV-I associated myelopathy (HAM). In spinal cords
      from autopsied patients with HAM/TSP, apoptosis of helper-inducer T lymphocytes
      was observed. HTLV-I carrier WKAH rats developed myeloneuropathy and apoptotic
      death of oligodendrocytes. The apoptosis was consistent with HTLV-I pX
      expression.

PMID- 8741679
TI  - [Ice/ced-3 family gene and apoptosis].
AB  - Apoptosis is a process by which cells carry out their own execution by activating
      an orderly set of genetic and biochemical program. A genetic pathway of apoptosis
      has been identified in the nematode Caenorhabditis elegans. The ced-3 gene is
      required for all programmed cell death in C. elegans. Mammalian homolog of ced-3
      has been identified as Ice family which is newly identified cysteine protease.
      Overexpression of Ice/ced-3 family gene can induce apoptosis in a variety of
      mammalian cells, and inhibitors of Ice/ced-3 family effectively prevent apoptosis
      induced by a variety of stimulus. Several housekeeping genes have been shown to
      be targets of Ice/ced-3 family gene, indicating that activation of Ice/ced-3 can
      induce irreversible fatal changes of cells.

PMID- 8741680
TI  - [Apoptosis induced by myc family genes].
AB  - Recent studies have revealed that c-Myc is involved not only in cellular
      transformation but also in apoptosis induction. However, the intronless myc
      family genes such as s-myc, N-myc2, mycL2 lack transforming ability and retain
      only apoptosis inducing activity. Although much remains to be clear regarding the
      molecular mechanism of apoptosis induction by myc gene expression, our recent
      results suggest that the intronless myc genes significantly differ from that of
      the c-myc gene in their requirement for wild-type p53 activity in apoptosis
      induction. We introduce here recent reports on Myc-mediated apoptosis and discuss
      its molecular mechanism.

PMID- 8741681
TI  - [Overexpression of c-Fos induces apoptosis of CD43+ pro-B cells].
AB  - The proto-oncogene product c-Fos, a component of the transcription factor AP-1,
      is induced in early B lineage cells. In order to investigate a role of the c-Fos
      in early B cell development, fetal liver (FL) cells from transgenic mice carrying
      an IFN-inducible c-fos gene (Mx-c-fos) were cultured on a stromal cell layer with
      IL-7. The development was perturbed by the addition of IFN at the beginning of
      culture. When IFN was added in the FL culture after B lineage cells developed,
      pro-B (B220+, CD43+) cells were selectively dying by apoptosis within 48 h after
      IFN stimulation. These results suggest that c-Fos plays a causal role in deletion
      of pro-B cells.

PMID- 8741682
TI  - [Role of the p53 gene in apoptosis].
AB  - Cell numbers are controlled by a homeostatic mechanism between cell growth,
      arrest and programmed cell death (apoptosis) in normal and cancerous tissues. One
      of the tumor suppressor genes, p53, functions as a transcription factor or
      transcriptional regulator through DNA and protein binding properties, and plays
      an important role in regulating cell cycle and induction of apoptosis. Although
      there are two apoptotic pathways, p53-independent and p53-dependent, the latter
      will be emphasized and discussed in this section. Since p53 is often inactivated
      due to mutation in human cancers, understanding the p53-dependent apoptotic
      pathway is extremely important. Analysis of p53-dependent apoptosis as well as
      apoptosis caused by other p53-related genes should provide a clue to a new
      strategy for cancer therapy.

PMID- 8741683
TI  - [TNF/TNFR gene and apoptosis].
AB  - Intracellular signal transduction pathways induced by in the reaction of TNF and
      TNF receptors has been clarified through finding of various TNF receptor
      associated intracytoplasmic molecules. The possible role of these signal
      transduction pathways for apoptosis induced by TNF is discussed.

PMID- 8741684
TI  - [Prevention of cell death by Bcl-2 family genes].
AB  - Apoptosis is a tightly regulated and evolutionally conserved suicide mechanism.
      Proteases encoded by ced-3 and ice gene family appear to play a key role in
      driving apoptosis. On the other hand, Bcl-2 and its relatives have the ability to
      inhibit apoptosis induced by a variety of stimuli, indicating that Bcl-2 family
      negatively regulates a key event in a common pathway of apoptosis in which
      different apoptotic signals finally converge, although the biochemical basis of
      the function remains unknown. Here, I overview Bcl-2 gene family, and discuss the
      molecular basis of anti-apoptotic activity of Bcl-2, focusing on our recent
      findings on Bcl-2 function in mitochondria.

PMID- 8741685
TI  - [Apoptosis related gene, Pim-1].
AB  - Pim-1, a protooncogene product, induced tumor in the combination with MYC. So
      far, two reports were published concerning Pim-1 function to apoptosis. One was
      that Pim-1 inhibit apoptosis in Pim-1 introduced transgenic mouse with a
      background of lpr/lpr, in which Fas was abrogated. However, the other that Pim-1
      induced apoptosis in a transient expression system was also reported. In this
      communication, we survey the possible functions of Pim-1 in terms of the factor
      related to apoptosis and carcinogenesis.

PMID- 8741686
TI  - [Inhibition of apoptosis by a baculovirus p35 gene].
AB  - The baculovirus gene p35 inhibits virus-induced apoptosis in insect cells. p35
      can also inhibit developmentally programmed cell death in Caenorhabditis elegans
      and Drosophila, mammalian neuronal cell death induced by serum or NGF
      deprivation, and Fas- and tumor necrosis factor (TNF)-induced apoptosis in
      mammalian cells, indicating that p35 may interrupt an evolutionally conserved
      component of the death machinery. Recently it has been shown that p35 protein
      functions as an inhibitor of ICE/CED-3 cysteine protease family that seem to play
      an important role in an apoptotic pathway. This observation indicates that p35
      may inhibit apoptosis by directly blocking the activities of these cysteine
      proteases in diverse animals.

PMID- 8741687
TI  - [Detection of apoptosis and expression of Fas antigen in human colorectal
      cancer].
AB  - The occurrence of apoptosis in formalin-fixed, paraffin-embedded human colorectal
      cancer tissues was investigated at a cellular level by in situ nick translation
      (ISNT). Then the frequency of ISNT-positive nuclei was compared with the
      proliferative activity assessed by proliferating cell nuclear antigen (PCNA)
      labeling index, and with the incidence of Fas positive cells examined
      immunohistochemically with the incidence of Fas positive cells examined
      immunohistochemically with rabbit anti-Fas serum. As a result, although no
      significant correlation between the frequency of apoptosis and the proliferative
      activity was observed, a balance between them may explain a variety of growth
      rates of colorectal cancers. As for Fas expression, about 33% of the colorectal
      cancers were more or less positive for Fas antigen.

PMID- 8741688
TI  - [Apoptosis and cell growth fraction in normal, dysplastic and neoplastic squamous
      epithelium of uterine cervix].
AB  - The populations of cells in apoptosis as well as proliferating cycle were
      examined in normal cervical epithelium, dysplastic change, carcinoma in situ and
      invasive carcinoma. The percentage of apoptotic cells (% Apo) decreased with the
      neoplastic change and was significantly lower in carcinoma in situ group than in
      the dysplasia group. Conversely, the percentage of cells in proliferating cycle
      (% GF) increased with the neoplastic change and was significantly higher in the
      dysplasia group than in the normal group. In the dysplasia group, the % Apo was
      lower in cases with HPV 16 infection or with bcl-2 expression, and the % GF was
      higher in cases with p53 expression. In conclusions, the decrease in apoptosis
      may reflect the atypical change in cervical epithelial cells during their
      neoplastic change, and the proliferative activity in neoplastic lesion was found
      when the cervical epithelium with dysplastic change was transformed to the
      carcinoma in situ. Furthermore, these events were related to the p53 accumulation
      and bcl-2 expression following the HPV 16 infection.

PMID- 8741689
TI  - [Expression of apoptosis-related gene products in human brain tumors and
      apoptosis-inducing therapy].
AB  - To elucidate the mechanism of apoptosis in brain tumors, we analyzed the
      expression of apoptosis-related gene products in cultured glioma cells and
      biopsied brain tumor specimens. Fas, Bcl-2 family (Bcl-2, Bcl-x and Bax) and ICE
      family (ICE, Ich-1) were found to be involved in tumorigenesis of certain brain
      tumors. It was also clarified that OK-432 activated mononuclear cells could kill
      T98G glioblastoma cells by apoptotic mechanism through the Fas ligand/Fas system.

PMID- 8741690
TI  - [Expression of Bcl-2 and Bax in human gastric cancer tissue].
AB  - Deregulation of bcl-2 may function as a survival mechanism in cancer cells,
      predisposed to cell death. Aberrant Bcl-2 expression is a frequent occurrence in
      chronic atrophic gastritis, gastric epithelial dysplasia and gastric cancer.
      Inhibition of apoptosis through Bcl-2 expression appears to be specifically
      associated with promotion of gastric adenocarcinoma. In addition, loss of
      heterozygosity of the bcl-2 gene is a common event in well-differentiated
      adenocarcinoma, whereas overexpression of bcl-2 gene is observed in poorly
      differentiated adenocarcinoma. Bax, a homologue of Bcl-2, counters the death
      repressor activity of Bcl-2. In our study Bax immunostaining in gastric cancer
      tissue is not significantly correlated with tumor histology. Possible gene
      therapy using bax gene is discussed.

PMID- 8741691
TI  - [Cancer chemotherapy and apoptosis].
AB  - Tumor cells undergo apoptotic cell death when treated with several
      chemotherapeutic agents. Since these agents, acting on different cellular
      targets, induce a similar pattern of cell death (apoptosis), it is suggested that
      a common signaling pathway of apoptosis could exist and that apoptosis resistance
      could cause a new form of multi-drug resistance in tumor cells. Although the
      mechanisms of apoptosis are not fully understood, the involvement of ICE/ced-3
      family proteases in chemotherapy-induced apoptosis is strongly suggested.
      Identification of factors directly acting on these apoptosis pathway will offer
      new strategies in cancer chemotherapy.

PMID- 8741692
TI  - [Radiation induced apoptosis in cultured human epithelial tumor cells].
AB  - The mode of cell death in cells undergoing mitotic death after irradiation was
      studied in twenty cancer cell lines of human gastrointestinal origin. Apoptotic
      cells were observed in all cancer cell lines after irradiation, whereas two
      fibroblast strains were quite low in apoptosis frequency. The advent of apoptosis
      depended on the radiation doses and incubation time. Detailed analysis of one of
      the carcinoma lines, SH101-P4, revealed that G2 phase arrest was maximum at 12 h
      postirradiation. The cells began to escape G2 arrest by 24 h. Apoptotic cells
      began to increase at 12 h postirradiation and became maximal from 72 to 96 h.
      Apoptosis developed in the G1 phase of the cell cycle subsequent to the
      irradiation. Moreover, the rate of apoptosis of the cells by irradiation did not
      correlate with p53 gene abnormalities. These results suggest that apoptosis is
      one of the modes of mitotic death after irradiation.

PMID- 8741693
TI  - [Characteristics of hyperthermia-induced apoptotic cell death].
AB  - Hyperthermia shows considerable promise as a treatment modality for cancer. It is
      widely accepted that hyperthermia at doses that fall within the therapeutic range
      triggers cell death by apoptosis in susceptible cell populations, higher heat
      loads producing necrosis. The hyperthermia-induced apoptosis is characterized
      both by its distinctive ultrastructural features and by the occurrence of
      internucleosomal DNA cleavage. The thermosensitivity to apoptotic induction
      varies enormously from cell type to cell type. The molecular mechanism which
      makes a cell sensitive to induction of apoptosis by hyperthermia is not at
      present clear, however, understanding why some cell types are sensitive or
      resistant to apoptotic induction is important to achieve the immediate cell
      killing effect of hyperthermia on each individual cell type.

PMID- 8741694
TI  - [Abnormal Fas and Fas ligand expression of lymphocytes in patients with SLE].
AB  - Fas and Fas ligand (FasL) have been assigned a pivotal role for establishment and
      maintenance of peripheral tolerance of immune system, and mice having defects in
      Fas/FasL genes develop diseases resembling human systemic lupus erythematosus
      (SLE). It has been reported that Fas expression of circulating lymphocytes is
      enhanced in patients with SLE. Nonetheless, apoptosis of SLE lymphocytes is not
      accelerated. Expression of FasL was detected marginally in unstimulated
      lymphocytes in normal individuals. In contrast, freshly isolated SLE lymphocytes
      showed enhanced expression of FasL without in vitro stimulation. We also found
      the presence of circulating anti-FasL autoantibody in patients with SLE. These
      results suggest that aberrant FasL expression of lymphocytes and anti-FasL
      autoantibody are, at least in part, involved in the immune-abnormalities and
      pathogenesis of the disease.

PMID- 8741695
TI  - [Expression of Fas/Fas ligand and proto-oncogenes in rheumatoid synovial
      tissues].
AB  - Expression of Fas antigen and Fas ligand (-L) were observed in synovial tissue
      from rheumatoid arthritis (RA) patients, whereas in only a few cells expressed
      these molecule osteoarthritis synovial tissue. Fas-L was expressed on CD45RO,
      CD4, CD8 or CD56 positive cells in RA synovial tissue. Moreover, 10 to 30% of
      synovial cells expressing Fas antigen were observed to be identical with
      apoptotic synovial cells and Fas expression was closely related to c-fos and c
      myc. These findings suggest that activated T cells and natural killer cells
      infiltrating into the RA synovium may play an important role in the induction of
      apoptosis of RA synovial cells through Fas/Fas-L interactions.

PMID- 8741696
TI  - [Involvement of Fas and Fas ligand in case of human fulminant hepatitis].
AB  - Fas antigen has been found to be a cell surface molecule which can induce
      apoptosis. Since it has been reported that administration of anti-Fas monoclonal
      antibody into mouse peritoneal cavity causes fulminant hepatitis (FH) in vivo,
      the Fas-Fas ligand system is thought to play important roles in massive
      hepatocytes death in FH. In murine system, there are several reports which showed
      Fas-Fas ligand system involved in FH. In human, the expression of Fas antigen was
      markedly increased on the cell surface of the hepatocytes and Fas ligand was
      expressed on the hepatic infiltrated lymphocytes. It is suggested that the Fas
      Fas ligand system also play important roles in human FH.

PMID- 8741697
TI  - [Expression of Fas and Fas-ligand in epithelium of ulcerative colitis].
AB  - Ulcerative colitis (UC) is characterized by the loss of epithelium and
      inflammation of lamina propria. In normal colon, epithelial cells are eliminated
      by apoptosis at the luminal surface. The apoptotic cells recognized by their
      typical morphology and the presence of DNA breaks are also accompanied by Fas and
      Fas-ligand. It is thought when Fas-ligand bound the Fas, the cells bearing Fas
      will enter a path of apoptosis. On the other hand, in inflamed areas of UC and
      adjacent un-inflamed areas, the apoptosis of epithelial cells are recognized
      anywhere along crypts. These findings suggest that unscheduled apoptosis in the
      UC crypts takes place and the apoptosis is mediated by a auto- or paracrine
      Fas/Fas-ligand interaction.

PMID- 8741698
TI  - [Role of apoptosis in renal injury].
AB  - Nephrologists are now investigating the involvement of apoptosis, or programmed
      cell death, in various renal diseases. Evidence suggests that abnormalities of
      apoptosis may contribute to the development of glomerular and tubular diseases.
      In tissue remodeling after glomerular injuries, excess apoptosis may be
      associated with cell deletion of glomerular sclerosis. Increased apoptosis may
      mediate the resolution of glomerular hypercellularity in experimental mesangial
      proliferation. Reactive oxygen species, deprivation of growth factors, anti-Thy 1
      monoclonal antibodies and anti-Fas antibodies are capable of inducing apoptosis
      in cultured mesangial cells. In renal tubular diseases, apoptosis may be
      associated with tubular atrophy after ureteral obstruction, tubular damage after
      ischemia-reperfusion or toxic drugs, and the development of polycystic kidney
      disease. Infiltrative leukocytes in the glomerulus and renal interstitium undergo
      apoptosis during inflammation. Thus, apoptosis appears to play a significant role
      in many renal diseases, and we should consider the regulation of apoptosis in the
      treatment of these disorders.

PMID- 8741700
TI  - [Fas antigen (CD95) expressions and apoptosis of neoplastic cells from various
      lymphoid malignancies including adult T-cell leukemia/lymphoma].
AB  - We determined Fas antigen (CD95) expressions on neoplastic cells from various
      lymphoid malignancies including adult T-cell leukemia/lymphoma (ATL/L) by a flow
      cytometoric method. ATL/L cells generally expressed Fas antigen, while few Fas
      positive cells were detected in the other lymphoid malignancies such as non
      Hodgkin lymphomas, acute lymphoblastic leukemias, and chronic lymphocytic
      leukemias. The function of Fas antigen was considered normal, since anti-Fas
      monoclonal antibody induced apoptosis of ATL/L cells. However, clinical subtypes
      of ATL/L did not associate with the degrees of Fas antigen expression. When
      recent observations by others were also considered, the apoptosis of ATL/L cells
      seemed to be under a complex control mechanism which includes a Fas/Fas-ligand
      system, HTLV-I Tax protein, bcl-2 protein and interleukin-2 (IL-2)/IL-2 receptor
      system. In addition, the regulation of apoptosis by Fas/Fas-ligand system and bcl
      2 protein might be different between T-and B-lineage lymphoid malignancies.

PMID- 8741699
TI  - [Apoptosis in the process from viral myocarditis to dilated cardiomyopathy].
AB  - Detection of viral genomic RNAs in myocardium of dilated cardiomyopathy (DCM)
      suggested the relationship between DCM and viral myocarditis. The viral infection
      may cause cytokine expression followed by induction of inducible nitric oxide
      synthase (iNOS) and expression of Fas antigen. The iNOS has potent and long
      lasting effects on NO generation, has cytotoxic effects and triggers apoptosis in
      car diomyocytes. In addition, the expression of Fas antigen directly induces
      apoptosis.

PMID- 8741701
TI  - [Fas antigen is expressed in human diseased muscles, but does not link to
      apoptosis].
AB  - In an attempt to determine whether the Fas-Fas-ligand mediated apoptosis occurs
      in the pathologic process of human myopathies, we examined the expression of Fas
      antigen, Fas-ligand mRNA, and chromosomal DNA fragmentation in the muscle cells
      of several human muscle disorders. The Fas antigen of a whole molecule was
      expressed on the muscle fibers of patients with muscle wasting diseases. However,
      there was no evidence of an apoptotic process, nor Fas-ligand synthesis in the
      diseased muscle tissue. Therefore, the expression of Fas antigen on muscle fibers
      in diseased muscle might be related to unknown biological functions other than
      "apoptosis" in the process of muscle fiber injury.

PMID- 8741702
TI  - [Synthetic vectors for gene transfection].
AB  - Although viruses can be efficient gene transfer vehicles developed by natural
      evolution, progress also has been made toward developing nonviral gene delivery
      systems. Various methods for nonviral gene transfer have been proposed and shown
      to be generally safe. Basically, synthetic vectors have to be capable of binding
      to DNAs and carrying them inside into target cells. Synthetic vectors are
      classified into three groups with respect to the chemical structure: cationic
      lipids, ligand-polycation conjugates and polycationic polymers. In this review,
      we summarize their ability to mediate gene transfer in relation to their
      structural characteristics. Although the molecular mechanisms including
      internalization via cell membrane and nuclear transport are still poorly
      understood, in the future systematic studies on the structure-activity
      relationship will be helpful for the design of more efficient artificial vectors.

PMID- 8741703
TI  - [Recent trends in drug delivery systems using biomaterials].
AB  - Since the concept of sustained release of biologically active agents was
      established in 1970's, the sustained release has been examined by controlling the
      diffusion of drugs through polymeric matrices and/or the degradation of these
      polymers. Recently, drug release in proportion to internal or external stimuli
      has been getting important, which can be achieved by using stimuli-responsive
      polymeric materials. Majority of these polymers have been designed as to achieve
      their functions by changes in temperature, pH, glucose concentration, and the
      release of ribosomal enzymes. Especially, among those materials, biodegradable
      polymers have much potential for applications as implantable carriers for drug
      delivery system (DDS). In an auto feed-back drug delivery, several physiological
      changes in a living body can be utilized as the signal inducing polymer
      degradation and subsequent drug release. A hydrogel composed of hydrophilic
      biomaterials has been focused because of their high responsibility to the
      stimulus. In this paper, currently investigated DDS using hydrogels are reviewed
      with their strategies.

PMID- 8741704
TI  - [Spotted fever group rickettsiosis and vectors in Kanagawa prefecture].
AB  - Primer pairs for PCR were designed from the gene encoding the 17,000-molecular
      weight genus-common antigen of Rickettsia japonica, Rickettsia rickettsii,
      Rickettsia conorii, Rickettsia typhi and Rickettsia prowazekii. Primers R1, R2
      were designed for amplifying the genomic DNA from spotted fever group (SFG)
      rickettsiae and epidemic typhus rickettsiae. Primers Rj5, Rj10 were designed for
      amplifying the genomic DNA from only R. japonica. Using the primers R1, R2, about
      a 540-bp fragment was observed by amplifying the genomic DNA from R. japonica, R.
      rickettsii, R. conorii, Thai tick typhus TT-118, Rickettsia sibirica, Rickettsia
      montana, Rickettsia askari, R. typhi, R. prowazekii and Katayama strain isolated
      from the patient infected with SFG rickettsiae. Using the primers Rj5, Rj10, the
      357-bp fragment was observed by amplifying the genomic DNA from R. japonica and
      Katayama strain. Therefore, the Katayama strain was identified to belong to R.
      japonica. With primers R1, R2 and Rj5, Rj10, 537 bp and 357 bp bands were
      amplified from blood of the patients infected with SFG rickettsiae in Kanagawa
      prefecture. These findings indicate that the causative agent of SFG rickettsiosis
      in these two patients was R. japonica. The ticks, Ixodes ovatus and Haemaphysalis
      flava, were collected by out field research in Kanagawa prefecture. With primers
      R1, R2 and Rj5, Rj10, 537 bp and 357 bp were amplified from these ticks. This
      indicates that I. ovatus and H. flava were the vector of R. japonica in Kanagawa
      prefecture. Also, with the primers R1, R2, about a 540 bp fragment was amplified
      but with primers Rj5, Rj10, no fragments were amplified from I. ovatus and H.
      flava. Therefore, these ticks may have SFG rickettsiae other than R. japonica and
      epidemic typhus rickettsiae.

PMID- 8741705
TI  - [PCR methods for detection of enteropathogenic Escherichia coli (localized
      adherence) and enteroaggregative Escherichia coli].
AB  - A PCR method was developed to detect enteropathogenic Escherichia coli (localized
      adherence) and enteroaggregative Escherichia coli. A portion of the structural
      gene (bfpA) encoding bundle-forming pilus (BFP), was amplified by the PCR for the
      detection of enteropathogenic Escherichia coli. It proved to be sensitive and
      specific in detecting enteropathogenic Escherichia coli. For the detection of
      enteroaggregative Escherichia coli, a portion of aggR (a transcriptional
      activator of aggA coding a major fimbrial subunit) was amplified. Although few
      strains showing non-aggregative adherence gave positive result, the PCR method
      was shown to have greater sensitivity than the probe assay in detecting
      enteroaggregative Escherichia coli.

PMID- 8741706
TI  - Enhancement of host resistance to bacterial infections in normal and
      immunosuppressed mice with Actinobacillus suis.
AB  - A single intraperitoneal (ip) inoculation of heat-killed Actinobacillus suis ATCC
      15,557 (AS 15,557) into normal and immunosuppressed (dexamethasone-treated) mice
      led to remarkable nonspecific resistance to ip challenge with lethal doses of
      opportunistic pathogens such as Pseudomonas aeruginosa, methicillin-resistant
      Staphylococcus aureus and Candida albicans. The duration of this enhanced
      protective action and the minimal effective dose, in normal mice, induced by AS
      15,557 were superior to those induced by other bacterial immunostimulants such as
      heat-killed Lavtobacillus casei YIT 9018 (LC 9018) and penicillin-treated
      Streptococcus pyogenes, Su (OK-432). In immunosuppressed mice; the reduced in
      vivo killing activity of peritoneal exudate cells (PECs) against P. aeruginosa
      infection was markedly augmented by ip injection of AS 15,557. The degree of PEC
      augmentation induced by AS 15,557 was higher than that induced by LC 9018 or by
      OK-432. The toxicity and histopathological changes associated with AS 15557 were
      very low, as compared with those by produced by LC 9018 and OK-432. The results
      suggest that AS 15,557, which showed a strong resistance-enhancing capacity
      against opportunistic bacterial infections, may be a useful bacterial
      immunostimulant.

PMID- 8741707
TI  - [Comparative susceptibility of 10 antimicrobials against Pseudomonas aeruginosa
      isolated from complicated urinary tract infection on 1992 & 1993 vs. 1994 &
      1995].
AB  - The susceptibility of 10 antimicrobials against P. aeruginosa isolated from
      complicated UTI during 1992-1995 was determined, and the yearly trend was
      examined. The drug tested included 3 cephems (ceftazidime [CAZ], cefpirome [CPR],
      cefclidin [CFCL]), 1 monobactam (aztreonam [AZT]), 2 carbapenem
      (imipenem/cilastatin [IPM/CS], biapenem [BIPM]), 2 aminoglycosides (netilmicin
      [NTL], gentamicin [GM]) and 2 new quinolones (ofloxacin [OFLX], ciprofloxacin
      [CPFX]). A total number of isolates of which MIC were determined was 77 in
      1992/1993 and 70 in 1994/1995. MIC50/MIC90(micrograms/ml) on the isolates were as
      follows (1992/1993 1994/1995); 3.13/ 100 12.5/50 in CAZ, 12.5/100 12.5/100 in
      CPR, 3.13/25 1.56/25 in CFCL, 6.25/50 12.5/100 in AZT, 6.25/25 3.13/25 in IPM/CS,
      1.56/6.25 0.78/50 in BIPM, 12.5/100 6.25/100 in NTL, 6.25/ 50 6.25/100 < in GM,
      25.100 < 25/100 < in OFLX, 6.25/100 6.25/100 < in CPFX. When the susceptibility
      of the yearly trend is compared, no significant changes were detected among the
      drugs tested expect the decrease of susceptibility on CAZ, AZT and increase of it
      on IPM/CS. From the data obtained, against complicated UTI infected by P.
      aerugunosa, CFCL, IPM/CS and BIPM are considered to drugs of first choice in the
      treatment.

PMID- 8741708
TI  - [Effect of macrolide antibiotics on airway goblet hypersecretion in guinea pigs].
AB  - Although macrolide antibiotics have now been widely used in the treatment of
      chronic airway infections including diffuse panbronchiolitis and chronic
      bronchitis, the mechanism of the efficacy remains uncertain. Because the
      increased mucus glycoprotein secretion from airway goblet cells may play a
      significant role in the development of such diseases, to determine the effects of
      macrolides on airway goblet cell secretion, we studied guinea pig airways by a
      semiquantitative morphometric method. The goblet cell secretion was assessed in
      histological sections of the trachea and main bronchi stained with Alcian blue
      and PAS by determining mucus score, which is inversely related to the magnitude
      of mucus discharge. Intravenous IL-8 decreased mucus score in a dose-dependent
      manner and increased the number of neutrophils present in bronchoalveolar lavage
      fluid. Oral administration of clarithromycin at a daily dose of 1-10 mg/day for 2
      weeks dose-dependently inhibited IL-8 (5 mg/ kg)-induced decrease in mucus score,
      with the maximal inhibition being 54 +/- 11% (p < 0.001) in the trachea and 48 +/
      8% (p < 0.01) in the main bronchi. This effect was accompanied by the inhibition
      of neutrophil accumulation into bronchoalveolar lavage fluid. Erythromycin
      produced similar inhibitory effects on IL-8-induced goblet cell secretion and
      neutrophil accumulation, whereas amoxicillin and cefaclor had no effect. These
      results suggest that macrolides protect against goblet cell hypersecretion
      probably through an inhibition of recruitment of neutrophils into the airway
      mucosa.

PMID- 8741709
TI  - Evaluation of interferon treatment in cirrhotic patients with hepatitis C.
AB  - The aim of this study was to examine the effects of interferon on cirrhotic
      patients with hepatitis C and the incidence of adverse reactions. The subjects
      were 35 cirrhotic patients, and 29 chronic active hepatitis patients without
      cirrhosis (CAH) served as controls. The cirrhotic patients received 3 or 6
      million units of human lymphoblastoid interferon daily for one or two weeks and
      then three times a week for 22 or 23 weeks, while the CAH patients received 6
      million units daily for 2 weeks and then three times a week for 14 or 16 weeks.
      Discontinuation of interferon treatment or dose reduction was required in the 7
      cirrhotic patients. The most frequent reason was thrombocytopenia. Dose reduction
      alone was necessary in two CAH patients. Five cirrhotic patients (14.3%) and nine
      CAH patients (31.0%) were classified as complete responders to interferon
      treatment. In all five complete responders with cirrhosis, the hepatitis C virus
      RNA level before treatment was less than 5 log copies/50 microliters. The results
      of this study confirm the beneficial effect of interferon in selected patients
      with cirrhosis on basis of pre-treatment virus levels and platelet count.

PMID- 8741710
TI  - [Drug-resistance patterns of clinical isolates of Pseudomonas aeruginosa in
      regard to their lipopolysaccharide-chain sizes].
AB  - Pseudomonas aeruginosa strains isolated from patients with different types of the
      infections each consisted of LPSs different in chain sizes. The drug
      susceptibility patterns of these strains of P. aeruginosa were investigated to
      clarify the relationship between the LPS-compositions and susceptibility to some
      kinds of anti-pseudomonal drugs. The susceptibilities of nineteen strains (seven
      long-LPS strains, four short-LPS strains and eight LPS-deficient strains) to
      piperacillin, ceftazidime, gentamicin, norfloxacin and polymyxin-B were
      determined and these strains were classified into six types (Types I-VI)
      according to their drug-resistance patterns. Six of the eight LPS-deficient
      strains were found to be highly resistant to gentamicin alone (Type IV). Four of
      the seven strains with the long-LPS and one strain with the short-LPS were
      resistant to three drugs such as piperacillin, ceftazidime and norfloxacin, and
      classified into Type I. These results indicated that the major part of the LPS
      deficient strains and the considerable part of the long-chain LPS strains of P.
      aeruginosa tested had each characteristic profile in the drug resistance. The
      outer membrane proteins of thirteen strains, consisting of different types of LPS
      compositions, were analyzed by SDS-PAGE. The strains belonging to the same types
      of the drug-resistance patterns were found to have similar OMP-profiles, although
      a few exceptions were found. beta-lactamase and gentamicin-inactivating
      activities were determined for piperacillin-resistant and gentamicin-resistant
      strains, respectively. Of the piperacillin-resistant strains tested, the activity
      of beta-lactamase was high in one (No. 8) only, low in four and not found in
      four. The results showed that degrees of resistance of P. aeruginosa strains
      tested to piperacillin did not correlate to their producibility of beta-lactamase
      except one strain. Of the nine gentamicin-resistant strains tested, the
      gentamicin inactivating activity was high in one (No. 30) only, moderate in six
      and low in two. These results suggested that the significant levels of
      piperacillin- or gentamicin-resistance of P. aeruginosa isolated tested might be
      expressed each due to their decreased abilities for drug-permeabilities in
      addition to drug-inactivating activities such as beta-lactamase or gentamicin
      modifying enzyme. In the case of some resistant strains, the resistance to
      piperacillin or gentamicin was not explained by the results of the present study.
      Therefore, we must investigate the possibility that other mechanisms participate
      in the resistance of these strains.

PMID- 8741711
TI  - [Analysis of HCV infection in patients with hemophilia].
AB  - Second generation antibodies of HCV, HCV-RNA, genotype and data of liver function
      were investigated with the purpose of better understanding the condition of the
      32 hemophiliac patients currently in our hospital. The results being: 1) The
      positivity ratio of second generation antibodies was 96.9% and a negative example
      occurred in only one infant born in 1990. 2) In the positive example of second
      generation antibodies, HCV-RNA positivity was 77.4%, which is extremely high
      result. 3) There are several kinds of genotypes, such as type I, type II, type II
      + III and type III. Type I is most commonly found in the younger generation. The
      possibly for this presence was suggested to be from imported blood products. 4)
      There were few findings of liver disorder in cases of HCV-RNA negative patients.
      Meanwhile, the presence of liver disorder was found in about 70% HCV-RNA
      patients. There is evidence of correlation between the level disorder and age of
      the patient. In general, initial infection for hemophiliac patients takes place
      early in life. Compared to non-hemophilia hepatitis C patients, the liver
      disorder occurs at all ages but is becoming more prevalent younger patients.
      Although not common, there were occasionally a few cases of liver disorder
      turning into cirrhosis of the liver in patients in their 30's.

PMID- 8741712
TI  - [Two cases of Listeria monocytogenes infection in Osaka Municipal Hospital].
AB  - We report two cases of sepsis and meningoencephalitis with listeriosis. They died
      in despite of administering sensitive antibiotics. A 2 day old girl was admitted
      to our hospital because of fever and cyanosis. Listeria monocytogenes type 4b was
      cultured from blood, CSF, throat, urine, ear. She was treated with twice exchange
      transfusion and sensitive antibiotics (ABPC, TOB), but died from DIC. A 48 year
      old man suddenly experienced an unconscious condition. A CSF culture grew L.
      monocytogenes type 1/2a. He was treated with sensitive antibiotics (ABPC, CEZ
      etc), but went bad conditions. Listeria infection of this cases developed as
      unfortunate infection.

PMID- 8741713
TI  - [Efficiency of combination chemotherapy and interferon-alpha therapy in a patient
      with AIDS-related cutaneous and gastrointestinal Kaposi's sarcoma].
AB  - A 40-year-old male was admitted to the hospital with acquired immunodeficiency
      syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP). Two months before
      admission the patient had a high fever, general fatigue and mild epigastic
      tenderness. On admission, physical examination revealed numerous small tumors on
      the head, gingiva, neck, nasal ala, anterior forehead, anterior thoracic,
      bilateral sole and bilateral lower limbs. At that time, the CD4 cell count was
      130/microliters. Upper GI endoscopy was performed because of sever epigastralgia
      and hematemesis. The gastric mucosa was diffusely nodular and erythematous with
      bleeding. This biopsy showed Kaposi's sarcoma, and the same findings were
      obtained from the duodenum, rectum and skin, AIDS with related cutaneous and
      gastrointestinal KS and PCP was diagnosed. We performed a combination of
      chemotherapy and Interferon-alpha therapy, and the KS almost completely
      disappeared within 3 months.

PMID- 8741714
TI  - [A case of neonatal herpes infection which proved to be a mixed infection of
      herpes simplex virus type 1 and type 2].
AB  - We encountered a case which proved to be a mixed infection of herpes simplex
      virus (HSV) type 1 and type 2 in retrospective terms by in situ hybridization
      (ISH) and polymerase chain reaction (PCR). The case was a male. The gestational
      age was 39 weeks and 2 days. The birth body weight was 3024 g. A fever developed
      from the age of 6 days and he was admitted to the neonatal intensive care unit at
      the age of eight days. AST was 1042 IU/L, and ALT 206 IU/L. In spite of
      treatment, the patient died at the age of 12 days. Using paraffin embedded
      tissues, we performed the ISH and PCR on the cerebrum, lungs, liver, spleen, bone
      marrow, adrenal gland, and kidneys. With the ISH, the lungs, liver, spleen and
      adrenal gland were both HSV type 1 and type 2. With the PCR, only the liver was
      positive for type 1, and the lungs, liver, spleen, and adrenal gland were
      positive for type 2. In the ISH, a probe showing a cross reaction between type 1
      and type 2 was used for type 1 probe this time. But a type 2 probe and PCR did
      not show a cross reaction. We concluded that this case confirmed the presence of
      mixed infection (HSV type 1 and type 2) in neonatal HSV infection.

PMID- 8741715
TI  - [A fulminating case of Edwardsiella tarda septicemia with necrotizing fasciitis].
AB  - A 67-year-old Japanese male, suffering from liver cirrhosis with hepatoma, was
      admitted to the Yokohama National Hospital because of ascites retention. On
      physical examination, his abdomen was massively distended with ascites and his
      lower extremities were edematous. Laboratory findings on admission revealed
      hypoalbuminemia, moderate icterus, pancytopenia and hepatitis C virus antibody
      positivity. After admission, abdominal distention and edema were improved with
      the use of diuretics. On the 15th day of hospitalization, the patient noted
      diarrhea and bowel movements that occurred 10 times a day. On the following day,
      his body temperature rose to over 39 degrees C. On the morning of the 17th day,
      he complained of severe pain in the right lower extremity. Swelling and erythema
      over his right lower leg were evident. The skin lesion spread rapidly over the
      knee and became necrotic. His right leg became increasingly swollen with the
      development of edema and hemorrhagic bullae. About 4 hrs after the emergence of
      the skin lesion, his blood pressure fell to less than 60 mmHg. Laboratory
      findings suggested disseminated intravascular coagulation and multiple organ
      failure due to serious bacterial infection. In spite of vigorous treatment
      including administration of antibiotics, dopamine, gabexate mesilate and plasma,
      he did not recover from the state of shock and died about 14 hrs after the
      appearance of leg pain. Bacterial culture of the blood and contents of the bullae
      grew a gram negative rod identified as Edwardsiella tarda (E. tarda).
      Histological findings showed necrotizing fasciitis. E. tarda has recently become
      recognized as a pathogenic bacteria, particularly in patients with an underlying
      illness. This is the first reported case of E. tarda septicemia with necrotizing
      fasciitis.

PMID- 8741716
TI  - [A case of invasive pulmonary aspergillosis accompanied with Aspergillus
      meningitis].
AB  - A 53-year-old female was admitted to our hospital complaining of chest pain and
      gait disturbance. Examinations on admission showed that she was immunocompetent
      except the negative tuberculin test. The chest X-ray showed infiltrative shadows
      with old tuberculous lesions in the bilateral upper lung fields. In CT, a mass
      lesion was revealed in the lesion, which destructed the fifth thoracic vertebra
      and invaded into the epidural space. She died of meningitis on the 18th day after
      admission. On autopsy, it was made clear that the mass lesion was caused by
      Aspergillus fumigatus, and that the meningitis was the result of the invasion of
      the fungus into the epidural space.

PMID- 8741717
TI  - Schistosoma mansoni infestation: an imported case of a Japanese patient.
AB  - A 25-year-old male Japanese who had resided in Ethiopia, presented to our
      department with eosinophilia, which had been present for about 1 year. Stool
      examination revealed eggs of Schistosoma mansoni containing miracidia with flame
      cell activity, and he was diagnosed as having an infestation with this organism.
      He was treated with praziquantel, and a good parasitological therapeutic result
      was obtained. Although schistosomiasis mansoni is unfamiliar to Japanese doctors
      because the infecting organisms are not indigenous to Japan, doctors should be
      aware of this disease when they encounter patients with eosinophilia who have
      visited or resided in tropical developing countries.

PMID- 8741718
TI  - One versus five sessions of applied tension in the treatment of blood phobia.
AB  - Thirty patients with blood phobia, fulfilling the DSM-III-R criteria for simple
      phobia, were assessed with behavioral, physiological and self-report measures.
      They were randomly assigned to 3 different conditions: (1) 5 sessions of applied
      tension; (2) 1 session of applied tension (maximum 2 h); and (3) I session of
      tension-only (maximum 2 h). The results showed that the patients in the 3
      treatments were all significantly improved at post-treatment and the effects were
      maintained at the 1 yr follow-up. At post-treatment and follow-up the proportions
      of clinically improved patients were: AT5 50 and 60%, AT1 0 and 70%, and T1 30
      and 60%, respectively. The conclusion that can be drawn is that I-session
      therapist-directed applied tension or tension-only is the treatment of choice for
      blood phobia, but completed with a maintenance program of self-exposure.

PMID- 8741719
TI  - Psychological treatments of panic disorder without agoraphobia: cognitive therapy
      versus applied relaxation.
AB  - This study compared two psychological treatments of panic disorder and tested
      whether cognitive therapy (CT) was superior to applied relaxation (AR); and
      whether treatment was superior to waiting. Thirty-six outpatients of the
      community mental health center with the DSM-III-R diagnosis of panic disorder
      with no or mild agoraphobia were randomly assigned to CT or AR. Eighteen similar
      patients who were referred after the treatment conditions were complete
      constituted a waiting-list group. Treatment consisted of 12 weekly sessions.
      Patients self-monitored panic attacks during the whole treatment period, and the
      following 4 weeks, and during 1 week at a half-year follow-up. Questionnaires
      were filled out before and after treatment, and at 4-week and half-year follow
      ups. After the first follow-up additional treatment was provided if clinically
      indicated. One patient dropped out of AR and was replaced. Treatment was superior
      to waiting in reducing panic and questionnaire scores. CT was clearly superior to
      AR in reducing panic frequency, and somewhat less strongly superior to AR in
      reducing the questionnaire scores. Depending on the assessment point, 77.8-83.3%
      of the CT patients was panic-free after treatment, compared to 50% of the AR and
      27.7% of the waiting-list patients. In conclusion, cognitive therapy for panic is
      especially effective in reducing the incidence of panic attacks.

PMID- 8741720
TI  - Delusional phenomenology--dimensions of change.
AB  - Although the application of cognitive techniques to both the measurement and
      modification of delusional beliefs has recently been developed in more
      theoretical detail (e.g. Chadwick & Lowe, 1994, Behaviour Research and Therapy,
      32, 355-367) there has not been an effort to examine the variability of
      delusional phenomenology across time. In the present study we report on the
      treatment of 6 individuals who fulfilled DSM-III-R (American Psychiatric
      Association, 1987) criteria for Delusional Disorder and who received cognitive
      therapy targeted specifically on the single symptom of their delusional
      belief(s). Single-case time-series methodology was used to examine the
      associations between different aspects of delusional phenomenology through
      baseline and intervention study phases. Belief maintenance factors were found to
      be significantly associated with conviction in all 3 individuals who responded to
      the intervention. Negative behaviours, affect associated with the belief,
      preparedness to talk to others about the belief and insight were associated with
      conviction in some individuals but not others. Preoccupation and acting on the
      belief were aspects of delusional phenomenology that were found to systematically
      vary independent of belief conviction. The results support a multidimensional
      view of delusional phenomenology and the process of change during cognitive
      intervention.

PMID- 8741721
TI  - The effects of immediate, delayed, and residual sympathetic activation on sexual
      arousal in women.
AB  - In a recent experiment, Meston and Gorzalka (1995) [Behaviour, Research and
      Therapy, 33, 651-664] demonstrated a facilitatory effect of sympathetic
      activation, via acute exercise, on female sexual arousal. The present
      investigation was designed to examine the time course of this effect. Thirty-six
      sexually functional women participated in two experimental sessions in which they
      viewed a neutral film followed by an erotic film. In one of these sessions, Ss
      were exposed to 20 min of intense exercise (stationary cycling) prior to viewing
      the films. Subjective (self-report) and physiological (photoplethysmograph)
      sexual arousal were measured at either 5 min, 15 min, or 30 min post-exercise.
      Acute exercise marginally decreased vaginal pulse amplitude (VPA) and had no
      effect on vaginal blood volume (VBV) responses to an erotic film when measured 5
      min post-exercise. At 15 min post-exercise, exercise significantly increased VPA
      and marginally increased VBV responses. At 30 min post-exercise, both VPA and VBV
      responses to an erotic film were marginally increased. Acute exercise had no
      significant effect on subjective perceptions of sexual arousal in any of the
      experimental conditions.

PMID- 8741722
TI  - The efficacy of complaints management training in facilitating benzodiazepine
      withdrawal.
AB  - The study aimed at evaluating the efficacy of complaints management training
      (CMT) compared to that of anxiety management training (AMT) in patients
      undergoing benzodiazepine withdrawal. CMT focused on techniques to alleviate
      reported withdrawal symptoms. Nineteen patients were randomly allocated either to
      CMT or to AMT. Both groups received 9 weekly treatment sessions and were assessed
      every other week. Withdrawal was designed to be gradual over the first 4 weeks.
      CMT proved more successful than AMT in terms of abstinence rate, reported number
      of severe withdrawal symptoms, depression and anxiety. At follow-up after 6
      months, there was no difference between groups in terms of abstinence rate.

PMID- 8741723
TI  - Implicit memory bias for threat in panic disorder: application of the 'white
      noise' paradigm.
AB  - We employed Jacoby's white noise paradigm to investigate implicit memory bias for
      threat in panic disorder and in normal control subjects. Subjects heard a series
      of neutral sentences (e.g. "The shiny apple sat on the table") and panic
      sentences (e.g. "The anxious woman panicked in the supermarket"). Implicit memory
      for this prior exposure was then tested by having subjects rate the volume of
      white noise accompanying the presentation of 'old' sentences intermixed with
      'new' sentences. Implicit memory for old sentences is revealed when subjects rate
      the white noise accompanying these sentences as less loud than noise accompanying
      new sentences. Results revealed that under low noise level, panic patients
      demonstrated an implicit memory bias for threat information, whereas control
      subjects did not. This differential priming effect suggests that information
      about threat may be automatically accessed in these patients.

PMID- 8741724
TI  - Revision of the Padua Inventory of obsessive compulsive disorder symptoms:
      distinctions between worry, obsessions, and compulsions.
AB  - The Padua Inventory (PI), a self-report measure of obsessive and compulsive
      symptoms, is increasingly used in obsessive compulsive disorder (OCD) research.
      Freeston, Ladouceur, Rheaume, Letarte, Gagnon and Thibodeau (1994) [Behaviour
      Research and Therapy, 32, 29-36], however, recently showed that the PI measures
      worry in addition to obsessions. In an attempt to solve this measurement problem,
      this study used a content distinction between obsessions and worry to revise the
      PI. The revision was constructed to measure five content dimensions relevant to
      OCD i.e. (1) obsessional thoughts about harm to oneself or others; (2)
      obsessional impulses to harm oneself or others; (3) contamination obsessions and
      washing compulsions; (4) checking compulsions; and (5) dressing/grooming
      compulsions. A total of 5010 individuals participated in the study, 2970
      individuals completing the PI and the Penn State Worry Questionnaire (PSWQ) and
      an additional 2040 individuals completing only the PI. The results provided
      support for the reliability and validity of the revision. In addition, the
      revision of the PI was more independent of worry, as measured by the PSWQ, than
      the original PI. Support was thus found for the validity of the content
      distinction between obsessions and worry. The importance of this content
      distinction is also discussed for the evaluation of other hypothesized
      distinctions between obsessions and worry.

PMID- 8741725
TI  - Criterion-related validity of a phallometric test for paraphilic rape and sadism.
AB  - Eight men admitting to sadistic fantasies or urges (fantasizers), 7 sadistic
      rapists (sadists), 14 nonsadistic rapists, 31 courtship-disordered men (men
      displaying exhibitionism, voyeurism, frotteurism, or a combination of these
      paraphilias), and 20 community controls were compared on their relative
      phallometric responses to stimuli depicting rape, violent rape, and nonsexual
      violence. This study extended previous research by including a group of men who
      admitted to having sadistic fantasies or urges, in contrast to rapists who are
      likely to deny any such interests because of possible legal or social sanctions,
      and by including a large comparison group of men with a paraphilia other than
      sadism. Criterion-related validity was greater after combining the sadistic and
      nonsadistic rapists: fantasizers, sadists, and rapists did not differ from each
      other; fantasizers differed from community controls in their relative responses
      to rape, violent rape, and nonsexual violence; rapists differed from community
      controls in their relative responses to violent rape and nonsexual violence; and
      courtship-disordered men differed from community controls in their relative
      responses to nonsexual violence.

PMID- 8741726
TI  - Relations between problem orientation and optimism, pessimism, and trait
      affectivity: a construct validation study.
AB  - This study investigated the construct validity of the Positive and Negative
      Problem Orientation scales of the Social Problem-Solving Inventory-Revised (SPSI
      R) by examining the relations between these scales and measures of optimism,
      pessimism, and trait affectivity. Consistent with expectations based on social
      problem-solving theory, positive problem orientation was found to have a
      relatively large amount of variance in common with optimism and positive
      affectivity, and negative problem orientation was found to share a large amount
      of variance with pessimism and negative affectivity, but not enough to be
      considered redundant in either case. Positive problem orientation was found to
      add significant incremental validity to the prediction of adaptive problem
      engagement coping even after partialing out the variance associated with optimism
      and positive affectivity. In addition, negative problem orientation was found to
      add unique variance to the prediction of psychological distress even after
      controlling for pessimism and negative affectivity.

PMID- 8741727
TI  - Ca2+ release from the sarcoplasmic reticulum compared in amphibian and mammalian
      skeletal muscle.
AB  - Puzzled by recent reports of differences in specific ligand binding to muscle
      Ca2+ channels, we quantitatively compared the flux of Ca2+ release from the
      sarcoplasmic reticulum (SR) in skeletal muscle fibers of an amphibian (frog) and
      a mammal (rat), voltage clamped in a double Vaseline gap chamber. The
      determinations of release flux were carried out by the "removal" method and by
      measuring the rate of Ca2+ binding to dyes in large excess over other Ca2+
      buffers. To have a more meaningful comparison, the effects of stretching the
      fibers, of rapid changes in temperature, and of changes in the Ca2+ content of
      the SR were studied in both species. In both frogs and rats, the release flux had
      an early peak followed by fast relaxation to a lower sustained release. The peak
      and steady values of release flux, Rp and Rs, were influenced little by
      stretching. Rp in frogs was 31 mM/s (SEM = 4, n = 24) and in rats 7 +/- 2 mM/s (n
      = 12). Rs was 9 +/- 1 and 3 +/- 0.7 mM/s in frogs and rats, respectively.
      Transverse (T) tubule area, estimated from capacitance measurements and
      normalized to fiber volume, was greater in rats (0.61 +/- 0.04 microns-1) than in
      frogs (0.48 +/- 0.04 micron-1), as expected from the greater density of T tubuli.
      Total Ca in the SR was estimated as 3.4 +/- 0.6 and 1.9 +/- 0.3 mmol/liter
      myoplasmic water in frogs and rats. With the above figures, the steady release
      flux per unit area of T tubule was found to be fourfold greater in the frog, and
      the steady permeability of the junctional SR was about threefold greater. The
      ratio Rp/Rs was approximately 2 in rats at all voltages, whereas it was greater
      and steeply voltage dependent in frogs, going through a maximum of 6 at -40 mV,
      then decaying to approximately 3.5 at high voltage. Both Rp and Rs depended
      strongly on the temperature, but their ratio, and its voltage dependence, did
      not. Assuming that the peak of Ca2+ release is contributed by release channels
      not in contact with voltage sensors, or not under their direct control, the
      greater ratio in frogs may correspond to the relative excess of Ca2+ release
      channels over voltage sensors apparent in binding measurements. From the marked
      differences in voltage dependence of the ratio, as well as consideration of
      Ca(2+)-induced release models, we derive indications of fundamental differences
      in control mechanisms between mammalian and amphibian muscle.

PMID- 8741728
TI  - The kinetics of inactivation of the rod phototransduction cascade with constant
      Ca2+i.
AB  - A rich variety of mechanisms govern the inactivation of the rod phototransduction
      cascade. These include rhodopsin phosphorylation and subsequent binding of
      arrestin; modulation of rhodopsin kinase by S-modulin (recoverin); regulation of
      G-protein and phosphodiesterase inactivation by GTPase-activating factors; and
      modulation of guanylyl cyclase by a high-affinity Ca(2+)-binding protein. The
      dependence of several of the inactivation mechanisms on Ca2+i makes it difficult
      to assess the contributions of these mechanisms to the recovery kinetics in situ,
      where Ca2+i is dynamically modulated during the photoresponse. We recorded the
      circulating currents of salamander rods, the inner segments of which are held in
      suction electrodes in Ringer's solution. We characterized the response kinetics
      to flashes under two conditions: when the outer segments are in Ringer's
      solution, and when they are in low-Ca2+ choline solutions, which we show clamp
      Ca2+i very near its resting level. At T = 20-22 degrees C, the recovery phases of
      responses to saturating flashes producing 10(2.5)-10(4.5) photoisomerizations
      under both conditions are characterized by a dominant time constant, tau c = 2.4
      +/- 0.4 s, the value of which is not dependent on the solution bathing the outer
      segment and therefore not dependent on Ca2+i. We extended a successful model of
      activation by incorporating into it a first-order inactivation of R*, and a first
      order, simultaneous inactivation of G-protein (G*) and phosphodiesterase (PDE*).
      We demonstrated that the inactivation kinetics of families of responses obtained
      with Ca2+i clamped to rest are well characterized by this model, having one of
      the two inactivation time constants (tau r* or tau PDE*) equal to tau c, and the
      other time constant equal to 0.4 +/- 0.06 s.

PMID- 8741729
TI  - Gating of Na channels in the rat cortical collecting tubule: effects of voltage
      and membrane stretch.
AB  - The gating kinetics of apical membrane Na channels in the rat cortical collecting
      tubule were assessed in cell-attached and inside-out excised patches from split
      open tubules using the patch-clamp technique. In patches containing a single
      channel the open probability (Po) was variable, ranging from 0.05 to 0.9. The
      average Po was 0.5. However, the individual values were not distributed normally,
      but were mainly < or = 0.25 or > or = 0.75. Mean open times and mean closed times
      were correlated directly and inversely, respectively, with Po. In patches where a
      sufficient number of events could be recorded, two time constants were required
      to describe the open-time and closed-time distributions. In most patches in which
      basal Po was < 0.3 the channels could be activated by hyperpolarization of the
      apical membrane. In five such patches containing a single channel
      hyperpolarization by 40 mV increased Po by 10-fold, from 0.055 +/- 0.023 to 0.58
      +/- 0.07. This change reflected an increase in the mean open time of the channels
      from 52 +/- 17 to 494 +/- 175 ms and a decrease in the mean closed time from
      1,940 +/- 350 to 336 +/- 100 ms. These responses, however, could not be described
      by a simple voltage dependence of the opening and closing rates. In many cases
      significant delays in both the activation by hyperpolarization and deactivation
      by depolarization were observed. These delays ranged from several seconds to
      several tens of seconds. Similar effects of voltage were seen in cell-attached
      and excised patches, arguing against a voltage-dependent chemical modification of
      the channel, such as a phosphorylation. Rather, the channels appeared to switch
      between gating modes. These switches could be spontaneous but were strongly
      influenced by changes in membrane voltage. Voltage dependence of channel gating
      was also observed under whole-cell clamp conditions. To see if mechanical
      perturbations could also influence channel kinetics or gating mode, negative
      pressures of 10-60 mm Hg were applied to the patch pipette. In most cases (15 out
      of 22), this maneuver had no significant effect on channel behavior. In 6 out of
      22 patches, however, there was a rapid and reversible increase in Po when the
      pressure was applied. In one patch, there was a reversible decrease. While no
      consistent effects of pressure could be documented, membrane deformation could
      contribute to the variation in Po under some conditions.

PMID- 8741730
TI  - Rectifying conductance substates in a large conductance Ca(2+)-activated K+
      channel: evidence for a fluctuating barrier mechanism.
AB  - In this study, we investigated the mechanism underlying the production of
      inwardly rectifying subconductance states induced in large conductance Ca(2+)
      activated K+ channels (maxi K(Ca) channels) by the small, homologous proteins,
      bovine pancreatic trypsin inhibitor (BPTI) and dendrotoxin-I (DTX). Low
      resolution bilayer recordings of BPTI-induced substates display excess noise that
      is well described by a beta-distribution characteristic of a filtered, two-state
      process. High-resolution patch recordings of maxi K(Ca) channels from vascular
      smooth muscle cells confirm that the BPTI-induced substate is actually comprised
      of rapid, voltage-dependent transitions between the open state and a nearly
      closed state. Patch recordings of DTX-induced substates also exhibit excess noise
      consistent with a similar two-state fluctuation process that occurs at rates
      faster than those measured for the BPTI-induced substate. The results indicate
      that these examples of ligand-induced substates originate by a fluctuating
      barrier mechanism that is similar to one class of models proposed by Dani, J.A.,
      and J.A. Fox (1991. J. Theor. Biol. 153: 401-423) to explain subconductance
      behavior of ion channels. To assess the general impact of such rapid fluctuations
      on the practical measurement of unitary currents by amplitude histograms, we
      simulated single-channel records for a linear, three-state scheme of C (closed)
      O(open)-S(substate). This simulation defines a range of transition rates relative
      to filter frequency where rapid fluctuations can lead to serious underestimation
      of actual unitary current levels. On the basis of these experiments and
      simulations, we conclude that fluctuating barrier processes and open channel
      noise may play an important physiological role in the modulation of ion
      permeation.

PMID- 8741731
TI  - On the one-sided action of amphotericin B on lipid bilayer membranes.
AB  - The one-sided action of the polyene antibiotic, amphotericin B, on phospholipid
      bilayer membranes formed from synthetic phosphatidylcholines (DOPC and DPhPC) and
      sterols (ergosterol and cholesterol), has been investigated. We found formation
      of well-defined ionic channels for both sterols and not only for ergosterol
      containing membranes (Bolard, J., P. Legrand, F. Heitz, and B. Cybulska. 1991.
      Biochemistry. 30:5707-5715). Characteristics of these channels were studied in
      the presence of different salts. It was found that the channels have comparable
      conductances but different lifetimes that are approximately 100-fold less in
      cholesterol-containing membranes than in ergosterol-containing ones. Channel
      blocking by tetraethylammonium (TEA) ions shows that TEA blockage of channels in
      the presence of cholesterol increases their lifetimes in analogy to the
      lengthening of lifetimes of protein channels blocked by local anesthetics (Neher,
      E., and J. H. Steinbach. 1978. J. Physiol. 277: 153-176). However, the effect of
      the blocker on single-channel conductance is very close for both sterols. The
      data support the classical model of amphotericin B pore formation from complexes
      initially lying on the membrane surface as nonconducting prepores. We explain the
      antibiotic's cytotoxic selectivity by differences in the lifetimes of the
      channels formed with different sterols and suggest that phosphatidylcholine
      sterol membranes can be used as a tool for rapid estimation of polyene antibiotic
      cytotoxicity.

PMID- 8741732
TI  - A slow component of intramembranous charge movement during sarcoplasmic reticulum
      calcium release in frog cut muscle fibers.
AB  - Cut muscle fibers from Rana temporaria were mounted in a double Vaseline-gap
      chamber and equilibrated with an end-pool solution that contained 20 mM EGTA and
      1.76 mM Ca (sarcomere length, 3.3-3.8 microns; temperature, 14-16 degrees C).
      Sarcoplasmic reticulum (SR) Ca release, delta[CaT], was estimated from changes in
      myoplasmic pH (Pape, P.C., D.-S. Jong, and W.K. Chandler. 1995. J. Gen. Physiol.
      106:259-336). The maximal value of delta[CaT] obtained during a depleting
      depolarization was assumed to equal the SR Ca content before stimulation, [CaSR]R
      (expressed as myoplasmic concentration). After a depolarization to -55 to -40 mV
      in fibers with [CaSR]R = 1,000-3,000 microM, currents from intramembranous charge
      movement, Icm, showed an early I beta component. This was followed by an I gamma
      hump, which decayed within 50 ms to a small current that was maintained for as
      long as 500 ms. This slow current was probably a component of Icm because the
      amount of OFF charge, measured after depolarizations of different durations,
      increased according to the amount of ON charge. Icm was also measured after the
      SR had been depleted of most of its Ca, either by a depleting conditioning
      depolarization or by Ca removal from the end pools followed by a series of
      depleting depolarizations. The early I beta component was essentially unchanged
      by Ca depletion, the I gamma hump was increased (for [CaSR]R > 200 microM), the
      slow component was eliminated, and the total amount of OFF charge was essentially
      unchanged. These results suggest that the slow component of ON Icm is not
      movement of a new species of charge but is probably movement of Q gamma that is
      slowed by SR Ca release or some associated event such as the accompanying
      increase in myoplasmic free [Ca] that is expected to occur near the Ca release
      sites. The peak value of the apparent rate constant associated with this current,
      2-4%/ms at pulse potentials between -48 and -40 mV, is decreased by half when
      [CaSR]R approximately equal to 500-1,000 microM, which gives a peak rate of SR Ca
      release of approximately 5-10 microM/ms.

PMID- 8741734
TI  - Gain control of synaptic transfer from second- to third-order neurons of
      cockroach ocelli.
AB  - Synaptic transmission from second- to third-order neurons of cockroach ocelli
      occurs in an exponentially rising part of the overall sigmoidal characteristic
      curve relating pre- and postsynaptic voltage. Because of the nonlinear nature of
      the synapse, linear responses of second-order neurons to changes in ligh
      intensity are half-wave rectified, i.e., the response to a decrement in light is
      amplified whereas that to an increment in light is compressed. Here I report that
      the gain of synaptic transmission from second- to third-order neurons changes by
      ambient light levels and by wind stimulation applied to the cerci. Transfer
      characteristics of the synapse were studied by simultaneous intracellular
      recordings of second- and third-order neurons. Potential changes were evoked in
      second-order neurons by a sinusoidally modulated light with various mean
      luminances. With a decrease in the mean luminance (a) the mean membrane potential
      of second-order neurons was depolarized, (b) the synapse between the second- and
      third-order neurons operated in a steeper range of the exponential characteristic
      curve, where the gain to transmit modulatory signals was higher, and (c) the gain
      of third-order neurons to detect a decrement in light increased. Second-order
      neurons were depolarized when a wind or tactile stimulus was applied to various
      parts of the body including the cerci. During a wind-evoked depolarization, the
      synapse operated in a steeper range of the characteristic curve, which resulted
      in an increased gain of third-order neurons to detect light decrements. I
      conclude that the nonlinear nature of the synapse between the second- and third
      order neurons provides an opportunity for an adjustment of gain to transmit
      signals of intensity change. The possibility that a similar gain control occurs
      in other visual systems and underlies a more advanced visual function, i.e.,
      detection of motion, is discussed.

PMID- 8741733
TI  - CFTR: the nucleotide binding folds regulate the accessibility and stability of
      the activated state.
AB  - The functional roles of the two nucleotide binding folds, NBF1 and NBF2, in the
      activation of the cystic fibrosis transmembrane conductance regulator (CFTR) were
      investigated by measuring the rates of activation and deactivation of CFTR Cl-
      conductance in Xenopus oocytes. Activation of wild-type CFTR in response to
      application of forskolin and 3-isobutyl-1-methylxanthine (IBMX) was described by
      a single exponential. Deactivation after washout of the cocktail consisted of two
      phases: an initial slow phase, described by a latency, and an exponential
      decline. Rate analysis of CFTR variants bearing analogous mutations in NBF1 and
      NBF2 permitted us to characterize amino acid substitutions according to their
      effects on the accessibility and stability of the active state. Access to the
      active state was very sensitive to substitutions for the invariant glycine (G551)
      in NBF1, where mutations to alanine (A), serine (S), or aspartic acid (D) reduced
      the apparent on rate by more than tenfold. The analogous substitutions in NBF2
      (G1349) also reduced the on rate, by twofold to 10-fold, but substantially
      destabilized the active state as well, as judged by increased deactivation rates.
      In the putative ATP-binding pocket of either NBF, substitution of alanine,
      glutamine (Q), or arginine (R) for the invariant lysine (K464 or K1250) reduced
      the on rate similarly, by two- to fourfold. In contrast, these analogous
      substitutions produced opposite effects on the deactivation rate. NBF1 mutations
      destabilized the active state, whereas the analogous substitutions in NBF2
      stabilized the active state such that activation was prolonged compared with that
      seen with wild-type CFTR. Substitution of asparagine (N) for a highly conserved
      aspartic acid (D572) in the ATP-binding pocket of NBF1 dramatically slowed the on
      rate and destabilized the active state. In contrast, the analogous substitution
      in NBF2 (D1370N) did not appreciably affect the on rate and markedly stabilized
      the active state. These results are consistent with a hypothesis for CFTR
      activation that invokes the binding and hydrolysis of ATP at NBF1 as a crucial
      step in activation, while at NBF2, ATP binding enhances access to the active
      state, but the rate of ATP hydrolysis controls the duration of the active state.
      The relatively slow time courses for activation and deactivation suggest that
      slow processes modulate ATP-dependent gating.

PMID- 8741735
TI  - Oxygen sensing by ion channels and chemotransduction in single glomus cells.
AB  - We have monitored cytosolic [Ca2+] and dopamine release in intact fura-2-loaded
      glomus cells with microfluoroimetry and a polarized carbon fiber electrode.
      Exposure to low PO2 produced a rise of cytosolic [Ca2+] with two distinguishable
      phases: an initial period (with PO2 values between 150 and approximately 70 mm
      Hg) during which the increase of [Ca2+] is very small and never exceeds 150-200
      nM, and a second phase (with PO2 below approximately 70 mm Hg) characterized by a
      sharp rise of cytosolic [Ca2+]. Secretion occurs once cytosolic [Ca2+] reaches a
      threshold value of 180 +/- 43 nM. The results demonstrate a characteristic
      relationship between PO2 and transmitter secretion at the cellular level that is
      comparable with the relation described for the input (O2 tension)output (afferent
      neural discharges) variables in the carotid body. Thus, the properties of single
      glomus cells can explain the sensory functions of the entire organ. In whole
      cell, patch-clamped cells, we have found that in addition to O2-sensitive K+
      channels, there are Ca2+ channels whose activity is also regulated by PO2. Ca2+
      channel activity is inhibited by hpoxia, although in a strongly voltage-dependent
      manner. The average hypoxic inhibition of the calcium current in 30% +/- 10% at 
      20 mV but only 2% +/- 2% at +30 mV. The differential inhibition of K+ and Ca2+
      channels by hypoxia helps to explain why the secretory response of the cells is
      displaced toward PO2 values (below approximately 70 mm Hg) within the range of
      those normally existing in arterial blood. These data provide a conceptual
      framework for understanding the cellular mechanisms of O2 chemotransduction in
      the carotid body.

PMID- 8741737
TI  - Lipids as axon guidance molecules?

PMID- 8741736
TI  - Characterization of oxalate transport by the human erythrocyte band 3 protein.
AB  - This paper describes characteristics of the transport of oxalate across the human
      erythrocyte membrane. Treatment of cells with low concentrations of H2DIDS (4,4'
      diisothiocyanatostilbene-2,2'-disulfonate) inhibits Cl(-)-Cl- and oxalate-oxalate
      exchange to the same extent, suggesting that band 3 is the major transport
      pathway for oxalate. The kinetics of oxalate and Cl- self-exchange fluxes
      indicate that the two ions compete for a common transport site; the apparent Cl-
      affinity is two to three times higher than that of oxalate. The net exchange of
      oxalate for Cl-, in either direction, is accompanied by a flux of H+ with
      oxalate, as is also true of net Cl(-)-SO4(2-) exchange. The transport of oxalate,
      however, is much faster than that of SO4(2-) or other divalent anions. Oxalate
      influx into Cl(-)-containing cells has an extracellular pH optimum of
      approximately 5.5 at 0 degrees C. At extracellular pH below 5.5 (neutral
      intracellular pH), net Cl(-)-oxalate exchange is nearly as fast as Cl(-)-Cl-
      exchange. The rapid Cl(-)-oxalate exchange at acid extracellular pH is not likely
      to be a consequence of Cl- exchange for monovalent oxalate (HOOC-COO-; pKa = 4.2)
      because monocarboxylates of similar structure exchange for Cl- much more slowly
      than does oxalate. The activation energy of Cl(-)-oxalate exchange is about 35
      kCal/mol at temperatures between 0 and 15 degrees C; the rapid oxalate influx is
      therefore not a consequence of a low activation energy. The protein phosphatase
      inhibitor okadaic acid has no detectable effect on oxalate self-exchange, in
      contrast to a recent finding in another laboratory (Baggio, B., L. Bordin, G.
      Clari, G. Gambaro, and V. Moret. 1993. Biochim. Biophys. Acta. 1148:157-160.);
      our data provide no evidence for physiological regulation of anion exchange in
      red cells.

PMID- 8741738
TI  - Neurotoxic reactions of CNS cells following gene transfer with defective herpes
      simplex virus (HSV-1) vector.
AB  - Defective herpes simplex virus (HSV-1) vector containing either the lac-z gene or
      the tyrosine-hydroxylase (TH) gene was added to primary rat neocortex cultures
      and gene transfer was assessed using immunohistochemical procedures. While we
      were able to confirm lac- and TH-expression in vitro, exposure to the vector was
      accompanied by marked neurotoxic reactions as indicated by severe cell loss in
      vitro. Furthermore, when genetically altered cells were implanted into the adult
      rat striatum, a few lac-z positive cells without neurites were present but not a
      single TH-expressing cell could be found. The value of the HSV-1 vector system to
      transfer genes in the adult rat brain should therefore be viewed with caution.

PMID- 8741739
TI  - Monosodium glutamate increases NGF and NPY concentrations in rat hypothalamus and
      pituitary.
AB  - The effects of MSG treatment on NGF and NPY levels were analysed in the
      hypothalamus, pituitary, adrenal, thyroid and testis of adult rats. Daily i.v.
      injections of MSG (1 g kg-1 for 1 week) induced an increase of NGF in the
      hypothalamus (control (C) = 378 +/- 54; saline (S) = 369 +/- 36; MSG = 479 +/- 35
      pg g-1 tissue; p < 0.001) and pituitary (C = 310 +/- 34; S = 376 +/- 114; MSG =
      576 +/- 98 pg g-1 tissue; p < 0.01). Hypothalamic and pituitary NPY
      concentrations were also altered in the MSG-treated rats. Compared with saline
      treated rats, the NPY concentration increased by 43% in the hypothalamus and
      37.5% in the pituitary of MSG-treated rats. No significant changes in NGF and NPY
      content were found in the adrenal or thyroid of treated animals. These results
      suggest that hypothalamic and pituitary NGF and NPY levels may be involved in the
      control of neuroendocrine functions that are affected by MSG treatment.

PMID- 8741740
TI  - Melatonin inhibits oxytocin and vasopressin release from the neurointermediate
      lobe of the hamster pituitary.
AB  - The aim of this investigation was to study whether melatonin affects the release
      of oxytocin and vasopressin by the pituitary neurointermediate lobe of the Syrian
      hamster in vitro. The effect of melatonin was studied on the unstimulated (pre-
      and post-K+ -stimulated) release of oxytocin and vasopressin and on the response
      to K+ stimulation. Melatonin significantly inhibited unstimulated release of
      these hormones in all concentrations (10(-11) M, 10(-9) M and 10(-7) M) studied.
      K+ -stimulated release of oxytocin and vasopressin was significantly decreased by
      the 10(-9) M dose of melatonin. It is concluded that melatonin is active in
      modifying the release of these peptides in the Syrian hamster neurointermediate
      lobe, as it has been previously demonstrated in the rat hypothalamus.

PMID- 8741741
TI  - In vivo and in vitro effects of neuropeptide K and neuropeptide gamma on the
      release of growth hormone.
AB  - There is anatomical and experimental evidence suggesting that tachykinins have a
      role in the regulation of secretion of anterior pituitary hormones. In this
      investigation, the effects of neuropeptide K and neuropeptide gamma on the
      secretion of GH were studied in vivo and in vitro. Injections of neuropeptide K
      into the third ventricle of freely moving, ovariectomized rats resulted in a
      significant increase of plasma GH, but neuropeptide gamma induced no significant
      changes in these levels, although it did induce a significant increase in GH
      pulse height. In vitro, neither neuropeptide K nor neuropeptide gamma had any
      apparent effect on GH release from hemipituitaries incubated for 2 h. These
      results suggest that neuropeptide K may have a modulatory function in the
      regulation of GH secretion from the anterior pituitary, through an action exerted
      at the hypothalamic level, and the effects of neuropeptide gamma seem to be more
      marginal.

PMID- 8741742
TI  - Rat brain corticosteriod receptors are modulated by septo-hippocampal cholinergic
      innervation.
AB  - Brain corticosteroid receptors are regulated by neural control as well as by
      adrenal hormones. In this study we tested the effect of septo-hippocampal
      cholinergic lesions on the binding capacity of corticosteroid receptors. Rats
      were injected with ibotenic acid into the medial septum, and hippocampal type I
      and type II, and hypothalamic type II corticosteroid receptors were measured 15
      days later. In lesioned animals the number of type I corticosteroid receptors in
      the hippocampus was increased and their affinity decreased. In the hypothalamus
      only an increase of type II corticosteroid receptors was observed. As expected,
      lesioned rats showed an increase in basal plasma corticosterone levels.

PMID- 8741743
TI  - Noradrenaline release in hypothalamus and ACTH secretion induced by central
      interleukin-1beta.
AB  - The effect of interleukin-1beta (IL-1beta, 10 ng per 5 mu l i.c.v.) on
      noradrenaline release in the hypothalamus of freely moving rats and on plasma
      ACTH levels has been studied, respectively by intracerebral microdialysis and
      radioimmunoassay. IL-1beta induced an early increase in noradrenaline (NA)
      release in the paraventricular nucleus (PVN) followed by a second long-lasting
      enhancement starting from 80 min, with a maximum at 140 min (187 +/- 14%). Heat
      denatured IL-1beta induced only the early increase without any other change at
      later times. IL-1beta did not significantly affect NA release in the area
      surrounding the PVN at any time. IL-1beta increased ACTH levels at 2 and 3 h.
      Indomethacin (10 mg kg(-1), i.p.) prevented the noradrenergic and ACTH responses.
      The NA system in the PVN plays a part in the mechanism controlling the ACTH
      response induced by IL-1.

PMID- 8741744
TI  - The interpeduncular nucleus regulates nicotine's effects on free-field activity.
AB  - Partial lesions were made with kainic acid in the interpeduncular nucleus of the
      ventral midbrain of the rat. Compared with sham-operated controls, lesions
      significantly (p < 0.25) blunted the early (<60 min) free-field locomotor
      hypoactivity caused by nicotine (0.5 mg kg(-1), i.m.), enhanced the later (60-120
      min) nicotine-induced hyperactivity, and raised spontaneous nocturnal activity.
      Lesions reduced the extent of immunohistological staining for choline
      acetyltransferase in the interpeduncular nucleus (p <0.025), but not for tyrosine
      hydroxylase in the surrounding catecholaminergic A10 region. We conclude that the
      interpeduncular nucleus mediates nicotinic depression of locomotor activity and
      dampens nicotinic arousal mechanisms located elsewhere in the brain.

PMID- 8741745
TI  - Specific and efficient gene transfer strategy offers new potentialities for the
      treatment of motor neurone diseases.
AB  - Several growth factors are candidates for the therapy of motor neurone diseases.
      However, there is no efficient, safe, and practicable administration route which
      hampers the clinical use of these potentially therapeutic agents. We show that
      specific and high yield gene transfer into motor neurones can be obtained by
      peripheral intramuscular injections of recombinant adenoviruses. These vectors
      are retrogradely transported from muscular motor units to motor neurone cell
      bodies. Gene transfer can thus be specifically targeted to particular regions of
      the spinal cord by appropriate choice of the injected muscle. The efficiency of
      gene transfer is high, with 58-100% of the motor neurones afferent to the
      injected muscle expressing the transgene. This new therapeutic protocol allows
      specific targeting of motor neurones without lesioning the spinal cord, and
      should avoid undesirable side effects associated with systemic administration of
      therapeutic factors.

PMID- 8741746
TI  - Age-related production of new granule cells in the adult dentate gyrus.
AB  - Unlike most neurones, the dentate granule cells continue to be produced in
      adults. Recently our study has demonstrated that a highly polysialylated neural
      cell adhesion molecule (NCAM-H) is a reliable molecular marker for newly
      generated and developing dentate granule cells. Here we examined age-related
      changes in the number of newly generated and developing granule cells. In rats
      injected with 5-bromo-2'-deoxyuridine (BrdU), a thymidine analogue, at 35 days to
      18 months of age, double immunohistochemistry for BrdU and NCAM-H showed that the
      numbers of NCAM-H-positive and BrdU-/NCAM-H-positive granule cells gradually
      decreased over more than one year, but they were still detected in 18-month-old
      rats. These findings indicate that newly formed and developing granule cells
      occur in the dentate gyrus of young and aged rats, but the number of these cells
      decreases with age.

PMID- 8741747
TI  - In vivo labeling of neuronal nicotinic acetylcholine receptors with radiolabeled
      isomers of norchloroepibatidine.
AB  - In vitro binding studies have shown that epibatidine and its norchloro analogues
      have high affinities for the cholinergic nicotinic receptor. In this study, the
      in vivo binding characteristics of [3H](+)norchloroepibatidine (NCEPB) and [3H](
      )NCEPB in mice were examined. After injection of [3H](+)NCEPB, radioactivity
      levels in all brain regions examined increased and then decreased, with different
      regions accumulating different levels of radioactivity. The regional distribution
      of radioactivity at later times paralleled the distribution of nicotinic receptor
      binding in vitro. The ratio of radioactivity in the superior colliculus to that
      in the cerebellum, a reflection or estimate of total: non-specific binding, was
      strikingly high at 8 h (about 35). Drugs known to bind to nicotinic receptors
      reduced [3H](+)NCEPB binding, while atropine and spiperone, muscarinic and
      dopaminergic drugs respectively, did not. [3H](-)NCEPB had a similar regional
      distribution to [3H](+)NCEPB. Pretreatment with increasing doses of non
      radioactive (-)NCEPB resulted in saturation of in vivo binding of [3H](-)NCEPB.
      These data indicate that [3H](+) and (-)NCEPB are useful in vivo binding ligands
      for the cholinergic nicotinic receptor.

PMID- 8741748
TI  - Patch-clamp study of neurones in rat olfactory cortex slices: properties of a
      slow post-stimulus afterdepolarizing current (IADP).
AB  - Whole-cell recordings were made from neurones in slices of rat olfactory cortex
      (10-19 days old), using potassium methylsulphate-filled pipettes. Positive
      commands applied from -60 mV in the presence of oxotremorine-M (10-20 microgramM,
      20 of 30 cells) or trans-ACPD (10-50 microgramM, 4 of 9 cells) evoked a slow
      inward tail current similar to the K+ -mediated tail current (I K,ADP) recorded
      with sharp electrodes. I ADP was reduced by hyperpolarization, showed a 27%
      decrease in input conductance at its peak and was depressed by Cd(2+), 4AP or
      high K+ but unaffected by Cs+, Ba(2+) or TEA (5 mM). IADP was significantly
      larger in cells between postnatal days 13 and 15 than in younger neurones (10-12
      days). These data show that stable whole-cell recordings of I ADP can be made
      from olfactory neurones in cortical slices, and support our hypothesis that IADP
      is a slowly reactivating, Ca(2+) -sensitive K+ conductance.

PMID- 8741749
TI  - Startle and sensorimotor correlates of ventral thalamic dopamine and GABA in
      rodents.
AB  - Recent studies have implicated the thalamus as a possible site for
      neuroanatomical and neurochemical changes in schizophrenia. In the present study,
      we investigated thalamic neurochemical correlates of behaviors potentially linked
      to schizophrenia. Whole thalamic DOPAC levels were elevated in rats that had poor
      extinction of the acoustic startle response. The dopamine agonist apomorphine
      microinjected into the ventromedial thalamus (VmT) disrupted prepulse inhibition
      of startle. Catalepsy was induced by VmT microinjections of the GABA-A agonist
      muscimol. A previous study revealed attentional disturbances and suppression of
      frontal cortical metabolic activity after muscimol microinjections into the
      mediodorsal thalamic nucleus. Together with recent findings of neuron cell loss
      and elevated DA levels in the thalamus of schizophrenics, these data suggest the
      involvement of disturbances of thalamic neurotransmission in schizophrenia.

PMID- 8741750
TI  - Glutamate agonist activity: implications for antipsychotic drug action and
      schizophrenia.
AB  - Antagonist action at dopamine D2 receptors appears to explain many, but not all
      of the effects of antipsychotic drugs. Because of the interactions of dopamine
      with glutamate, and the implication of the latter in the etiology of
      schizophrenia, possible effects of antipsychotic drugs on glutamate receptors
      were assessed in the present experiments. These studies showed that, at
      clinically relevant concentrations, the conventional neuroleptic haloperidol and
      the atypical antipsychotic clozapine had potent augmenting influences on the NMDA
      receptor. These data suggest that unique action at glutamate receptors may
      contribute to antipsychotic efficacy and emphasize the potential importance of
      glutamatergic dysfunction in the etiology of schizophrenia.

PMID- 8741751
TI  - D2-family receptor distribution in human postmortem tissue: an autoradiographic
      study.
AB  - The distribution throughout the normal human brain of the dopamine D2-family of
      receptors were investigated autoradiographically. Three ligands were used, [3H]
      YM-09151-2 to define the D2, D3, D4 receptors; [3H]raclopride the D2 D3
      receptors; and [3H](+)-7-OH-DPAT, in the presence of GTP, demonstrates D3
      distribution. [3H]-YM-09151-2 and [3H]raclopride binding were highest in caudate
      (121 vs 130 fmol mg(-1)), putamen (96 vs 136 fmol mg(-1)), and nucleus accumbens
      (113 vs 120 fmol mg(-1)). [3H]-YM-09151-2 also displayed significant binding in
      several cortical areas (56-39 fmol mg(-1)) and hippocampus (27 fmol mg-1).
      [3H](+)-7-OH-DPAT was highest in the nucleus accumbens. Based upon the ligands
      properties it is inferred that D2 distribution is highest in putamen, caudate and
      nucleus accumbens; D3 in the nucleus accumbens; D4 receptor in cortical areas and
      hippocampus.

PMID- 8741752
TI  - Ventilatory response to cholecystokinin tetrapeptide in anaesthetized dogs.
AB  - Cholecystokinin (CCK) has been implicated in the genesis of panic disorder. In
      this study we measured the ventilatory response to i.v. injection of CCK
      tetrapeptide (CCK-4) in anaesthetized dogs. We found an immediate and transient
      increase in minute ventilation. The response was large (more than 100% of
      baseline) and lasted 1-2 min. Repeated CCK-4 injection produced a somewhat
      reduced response, suggestive of a slight degree of tachyphylaxis. Blood pressure
      and heart rate changed only slightly (<10%), while respiratory mechanical
      parameters remained unchanged following CCK-4 administration. We conclude that
      CCK-4 has a significant effect on ventilation in the anaesthetized dog, which
      suggests that this species may provide a useful quantitative assay for the
      anxiogenic effects of CCK.

PMID- 8741753
TI  - Increased acetylcholinesterase activity in the CSF of Alzheimer patients carrying
      apolipoprotein epsilon4 allele.
AB  - We measured CSF acetylcholinesterase (AChE) activity in 57 Alzheimer's disease
      (AD) patients with different apolipoprotein E (apoE) genotypes at the early stage
      of the disease, and in 11 non-demented controls. The AChE activities of the whole
      AD group did not differ from those of controls. However, analysis of variance
      over the AD subgroups with two, one or no epsilon4 alleles and controls showed
      significant differences (p < 0.0001); the AD patients with two epsilon4 alleles
      had higher AChE activities than controls and AD patients with one or no epsilon4
      and also the AD patients carrying one epsilon4 allele had higher AChE activities
      than the AD patients without the epsilon4 allele. The study suggests that
      cholinergic metabolism is altered in proportion to the number of apoE epsilon4
      alleles. The different degree of AChE activity in relation to the number of
      epsilon4 alleles might have an impact on AD patients' responses to cholinesterase
      inhibitors.

PMID- 8741754
TI  - Stereotypies and loss of social affiliation after early hippocampectomy in
      primates.
AB  - The present study was aimed at determining whether early hippocampal damage
      alters the development of normal social interactions. Results showed that, at 2
      months of age, animals with neonatal hippocampal lesions presented minor
      disturbances in initiation of social interactions. These subtle changes in
      behavior were less evident at 6 months, although at this age, the operated
      animals displayed more withdrawals in response to an increase in aggressive
      responses from their unoperated peers. Finally, in adulthood, the amount of time
      spent by the operated monkeys in social contacts with their normal peers was
      markedly less than that in normal dyads. Only in adulthood did the operated
      animals exhibit more locomotor stereotypies than normal controls. This finding
      suggest that the hippocampal formation may directly or indirectly affect the
      maintenance of social bounds in primates.

PMID- 8741755
TI  - Origin of the dopaminergic innervation of the rat dorsal raphe nucleus.
AB  - The aim of the present study was to describe the distribution of dopamine (DA)
      fibres in the dorsal raphe nucleus (DRN) and to determine their neurones of
      origin. Using an anti-DA antibody, we observed a moderate density of DA varicose
      fibres over the DRN and a dense plexus of DA fibres in the ventrolateral central
      grey. With a sensitive retrograde tracing technique combining the use of cholera
      toxin subunit b with tyrosine hydroxylase immunohistochemistry, after tracer
      injections in the DRN, a few double-labelled cells were observed in the ventral
      tegmental area and the A10 dorsocaudal DA cell group, as already described. In
      addition, a moderate number of double-labelled cells was seen in the A11
      hypothalamic DA cell group.

PMID- 8741756
TI  - Pyramidal neurones in human precentral gyrus contain nitric oxide synthase.
AB  - Pyramidal cells in the mammalian neocortex do not normally contain detectable
      levels of the enzyme nitric oxide synthase. However one region of the human
      neocortex contains pyramidal neurones that express neuronal nitric oxide synthase
      activity. These neurons are mainly located in layer V of the precentral gyrus and
      frontal cortex and are predominantly Betz cells. The proportion of Betz cells
      stained in the eight brains examined varied from 5 to 80%. The brains of eight
      rats that had received a stab wound to the parietal cortex were also examined.
      Following a survival period of 7 or 14 days, small groups of pyramidal neurones
      surrounding the lesion contained moderate levels of neuronal nitric oxide
      synthase. We suggest that human pyramidal neurones may start expressing nitric
      oxide synthase as a response to damage or age-related stress and that the nitric
      oxide released may have a neuroprotective role.

PMID- 8741757
TI  - Regulation of prolactin receptor expression by estradiol in the female rat brain.
AB  - Prolactin (PRL) receptors have been identified in many tissues, including the
      brain, but little is known about their distribution and regulation. In the female
      rat brain, ovariectomy significantly (p < 0.05) decreased PRL binding capacity,
      but not the affinity, in the hypothalamus and pons-medulla. Using reverse
      transcription and polymerase chain reaction (RT-PCR) amplification and Western
      blot analyses we found both the long and short forms of the PRL receptor mRNAs
      and proteins in the hypothalamus, pons-medulla and cortex in the female rat.
      Ovariectomy decreased the expression of short, but not the long form of the PRL
      receptor in the hypothalamus and pons-medulla, but not the cortex. Administration
      of estradiol (1.0 mg per 100 g b.w.) restored the PRL binding capacity, protein
      and mRNA levels of the short form of the receptor back to control levels. These
      results suggest that the expression and distribution of PRL receptors in the
      brain are differentially regulated in specific brain regions.

PMID- 8741758
TI  - Expression of the phosphoinositide-specific phospholipase Cbeta3 gene in the rat.
AB  - Phospholipase Cbeta3 (PLCbeta3) is a member of the family of phospholipase C
      isoenzymes, a second messenger system that plays an important role in initiating
      receptor-mediated signal transduction in response to extracellular signals. Using
      RNA in situ hybridization we showed that in the embryonic rat nervous system,
      PLCbeta3 is expressed in dorsal root ganglia (DRGs) and the trigeminal ganglion.
      Characterization of the hybridization signal in the adult rat nervous system
      revealed that PLCbeta3 expression is confined mainly to small-sized DRG neurons.
      In non-neuronal tissues, PLCbeta3 is expressed by cells of epithelial origin,
      such as skin and the mucous lining airways and the gastrointestinal canal, and in
      lung and thymus.

PMID- 8741759
TI  - Selective down-regulation of 440 kDa ankyrinB associated with neurite retraction.
AB  - Brain-specific isoforms of ankyrin, 440 kDa and 220 kDa ankyrinB, which are
      generated from a single gene by alternative splicing of pre-mRNA, are both
      expressed in human neuroblastoma NB-1 cells and the expression of the larger
      isoform is increased upon induction of neurite outgrowth. Exposure to
      methylmercury, a potent neurotoxic substance, at a sublethal dose induced
      dramatic retraction of neurites in NB-1 cells. Concomitantly, synthesis of 440
      kDa ankyrinB polypeptide and mRNA were selectively attenuated in methylmercury
      treated cells, while the 220 kDa isoform was not affected. These results indicate
      that the expression of 440 kDa ankyrinB is intimately associated not only with
      the neurite outgrowth but also with neurite retraction in neuronal cells, and is
      regulated at mRNA level.

PMID- 8741760
TI  - AT1A, AT1B, and AT2 angiotensin II receptor subtype gene expression in rat brain.
AB  - We localized the gene expression of angiotensin II receptor subtypes (AT1A, AT1B,
      and AT2) in 2-week-old rat brain by in situ hybridization using subtype specific
      riboprobes. AT1A receptor mRNA but not AT1B or AT2 receptor mRNA was expressed in
      the subfornical organ and paraventricular nucleus of the hypothalamus. AT1B as
      well as AT1A receptor mRNA were found in the cerebral cortex and hippocampus.
      Conversely, AT2 receptor mRNA, but not AT1A or AT1B, was expressed in the medial
      geniculate nucleus and inferior olive. Our results indicate that AT1A receptors
      are involved in the well known central functions of angiotensin II. These results
      also support the hypothesis of the involvement of AT2 receptors in sensory and
      motor function.

PMID- 8741761
TI  - Zn(2+) permeates Ca(2+) permeable AMPA/kainate channels and triggers selective
      neural injury.
AB  - Brief exposures of cortical cultures to kainate (100 mu M) plus Zn(2+) (300 mu M)
      cause fluorescence of the Zn(2+) sensitive dye, TS-Q, to appear in virtually all
      neurons, probably reflecting depolarization and secondary Zn(2+) permeation
      through voltage-sensitive Ca(2+) channels. However, if Na+ ions are removed from
      the media (to prevent depolarization), prominent TS-Q fluorescence is still
      observed in the small subset of neurons labeled by kainate stimulated Co(2+)
      uptake (Co(2+)(+) neurons), a histochemical technique that identifies neurons
      expressing Ca(2+) permeable AMPA/kainate receptor-gated channels. Kainate/Zn(2+)
      exposures in Na+ containing media with lower (50-100 mu M) Zn(2+) concentrations
      resulted 24 h later in selective loss of the Co(2+)(+) neurons, suggesting that
      these channels may permit particularly high rates of Zn(2+) passage. Thus, direct
      permeation of synaptically released Zn(2+) through Ca(2+) permeable AMPA/kainate
      channels could contribute to selective degeneration of neurons in disease as well
      as subserving physiological signaling functions.

PMID- 8741762
TI  - The dioxin receptor and its nuclear translocator (Arnt) in the rat brain.
AB  - Dioxins are environmental pollutants, whose detrimental effects on health are the
      cause of wide public concern due to their accumulation in the food chain and
      resistance to metabolism. The most well known dioxin is 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). Dioxins exert their effects through a ligand
      activated transcription factor termed the dioxin or aryl hydrocarbon receptor
      (Ahr), which acts in concert with another structurally related protein: the aryl
      hydrocarbon nuclear translocator (Arnt). In the present study, we have employed
      in situ hybridization to study the localization of the mRNAs for these two
      proteins in the rat brain. We found mRNAs for both Ahr and Arnt predominantly in
      the same neuronal populations: in the olfactory bulb, the hippocampus, and the
      cerebral and cerebellar cortices. Arnt, however, had a more widespread expression
      than Ahr in the brain. The present results demonstrate that dioxins may act
      directly in the brain and that the effects of dioxin may occur in discrete
      neuronal populations. However, in some parts of the brain, e.g. the hypothalamus,
      that are thought to be targets of the toxic effects of dioxins, we did not
      observe detectable levels of Ahr mRNA. Furthermore, it appears that Arnt may have
      additional functions in the brain, apart from being the heterodimerization
      partner of Ahr, possibly through heterodimerizing with other transcription
      factors.

PMID- 8741763
TI  - Subthreshold membrane-potential oscillations in immature rat CA3 hippocampal
      neurones.
AB  - Subthreshold membrane potential oscillations (MPOs) were recorded intracellularly
      in 31 of 43 (>70%) immature CA3 hippocampal neurones (from 3-17 days
      postnatally). MPOs (3-5 mV, 3-15 Hz) occurred at resting membrane potential (RMP)
      in 20 of 31 neurones, or following depolarization (11 of 31 neurones); with
      sufficient depolarization spontaneous action potentials (APs) were generated from
      the positive-going phase of MPOs. In all cells, MPOs were blocked by steady
      membrane hyperpolarization. Tetrodotoxin abolished MPOs (n = 4); Co(2+) markedly
      reduced them (n = 3), and tetraethylammonium, added in the presence of TTX,
      revealed lower frequency oscillatory activity (n = 2). We conclude that
      subthreshold MPOs in immature hippocampus, possibly linked to theta rhythm
      generation and memory acquisition, depend on voltage-dependent Na+ electrogenesis
      and they might be additionally controlled by Ca(2+) and K+ conductances.

PMID- 8741764
TI  - Microstimulation of the supplementary eye field during saccade preparation.
AB  - Electrical stimulation of the supplementary eye field (SEF) of monkeys has been
      reported to evoke saccades with low threshold currents. In previous reports, the
      evoked saccades have appeared either as 'converging', 'goal directed', or at
      times 'constant vector'. In the present study, a new aspect of intracortical
      microstimulation (ICMS) was found when the stimulus was applied at the time when
      an animal was prepared to initiate its own voluntary saccades. A cue signal was
      given to the animal that indicated targets of impending saccades. After a
      variable delay period, a 'go' signal told the monkey to initiate the saccade
      toward the target. ICMS was applied shortly (50-100 ms) before the go signal. The
      stimulus-evoked saccades were directed toward and captured the cued target,
      provided that the target direction was contralateral to the cortical stimulus
      site. Saccades with that property were evoked only from a limited portion of the
      cortical field that corresponded to the SEF, characterizing this particular
      oculomotor area.

PMID- 8741765
TI  - Platelet-activating factor produces neuronal growth cone collapse.
AB  - It is generally believed that neuronal growth cone collapsing factors are
      proteins that interact with membrane-bound receptors. Platelet-activating factor
      (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine; PAF) - a phospholipid autocoid,
      also interacts with a membrane-bound neuronal receptor which is similar in nature
      to collapsing factor receptors. We report that PAF and the nonhydrolyzable PAF
      agonist, methyl carbamyl PAF (1-O-hexadecyl-2N-methylcarbamyl-sn-glycero-3
      phosphocholine, mc-PAF), evoke a dose-dependent neuronal growth cone collapse.
      This collapse is specifically attenuated by the PAF receptor antagonist BN-52021.
      These data point to a PAF receptor-mediated growth cone collapse. Therefore, PAF
      must be added to the list of collapsing factors which potentially guide axons to
      their proper targets in the developing nervous system.

PMID- 8741766
TI  - The cholinergic innervation of the adrenal gland and its relation to enkephalin
      and nitric oxide synthase.
AB  - Using a monoclonal antibody against rat brain choline acetyltransferase (ChAT)
      the cholinergic innervation of the adult rat adrenal gland was visualized. Almost
      all ChAT-positive fibres contained nitric oxide synthase (NOS), whereas
      enkephalin (ENK) was exclusively found in ChAT fibres among adrenaline chromaffin
      cells. The ChAT/NOS/ENK fibres disappeared after immunological sympathectomy,
      indicating a preganglionic origin. ChAT was not found in the superficial peptide-
      and NOS containing fibre plexus in the adrenal cortex or in small or large intra
      adrenal ganglion neurones under control conditions. Even after colchicine
      treatment only one single ChAT-positive small ganglion neurone was found. It is
      possible, therefore that some small intra-adrenal ganglion neurones, which
      express NOS- and VIP-like immunoreactivities, are noncholinergic, nonadrenergic
      neurones.

PMID- 8741767
TI  - Developmental expression of GAP43 mRNA in chromaffin cells and intra-adrenal
      neurons.
AB  - Growth associated protein 43 (GAP43) mRNA was found in scattered groups of
      chromaffin cells prenatally, and in chromaffin noradrenaline cells from postnatal
      day 6 (P6). The distinct adult distribution of GAP43 mRNA in chromaffin cells
      appeared between P10 and P16. High levels of GAP43 mRNA were found in intra
      adrenal ganglion neurons also expressing neuropeptide tyrosine (NPY) mRNA (type I
      ganglion neurons), and at prenatal and early postnatal stages in large medullarly
      clusters of NPY mRNA containing cells, probably representing type I ganglion
      neurons precursors. The expression of GAP43 mRNA in noradrenaline-producing
      chromaffin cells and type I ganglion neurons suggests an important role for GAP43
      in these cells both during development and in adult life.

PMID- 8741768
TI  - Modulation of neuropathic pain in rats by intrathecally injected serotonergic
      agonists.
AB  - The involvement of spinal cord serotonergic influences in the development of
      autotomy, a proposed behavioural model of denervation pain, was studied in rats
      subjected to sciatic and saphenous nerve transection 5 min after intrathecal
      injection of 100 or 200 mu g of several serotonergic receptor subtype agonists.
      Injection of 8-OH-DPAT, m-CPP, 2-m-5-HT and a low dose of 5-HT, significantly
      shifted one or more of the parameters describing autotomy to less intense
      behaviour. In contrast, the injection of CGS-12066B and DOI intensified autotomy.
      These results suggest both a modulatory role for spinal cord serotonin in the
      events occurring shortly after neurectomy and new therapeutic approaches for the
      prevention of certain pain syndromes, such as phantom limb pain.

PMID- 8741769
TI  - Activation of ipsilateral primary sensorimotor cortex by median nerve
      stimulation.
AB  - We report evidence for activation of ipsilateral primary sensorimotor cortex
      (SMI) after median nerve stimulation recorded with magnetoencephalography (MEG).
      We measured somatosensory evoked magnetic fields (SEFs) to median nerve
      stimulation with a 122-channel helmet-shaped magnetometer in 10 healthy subjects.
      In five, the magnetic field patterns suggested long-latency activation of the
      ipsilateral SMI. Source locations found by current dipole fitting corresponded to
      the SMI hand area, as determined by contralateral stimulation. Further evidence
      for the origin of the ipsilateral responses in SMI was provided by the
      suppression of these responses during movement of the contralateral fingers.
      Sensory input to ipsilateral SMI could play a role in sensorimotor integration of
      bilateral movements.

PMID- 8741770
TI  - Intrastriatal DNQX induces rotation and pallidal Fos in the 6-OHDA model of
      Parkinson's disease.
AB  - The 6-hydroxydopamine rat model of Parkinson's disease was combined with
      intracerebral drug infusions to examine the influence of glutamate receptors on
      striatal output activity. When infused into the dopamine-denervated striatum, the
      AMPA-kainate receptor antagonist DNQX dose-dependently elicited contralateral
      rotation and ipsilateral Fos immunoreactivity (Fos-IR) in the globus pallidus, a
      target nucleus of striatal output. DNQX did not elicit rotation or Fos-IR in
      unlesioned or partially lesioned rats. In addition, the NMDA receptor antagonist
      AP-5 failed to induce rotation and had minimal effects on pallidal Fos-IR in
      lesioned rats. These results suggest a role for striatal AMPA-kainate receptors
      in the pathology and treatment of Parkinson's disease.

PMID- 8741771
TI  - Vestibular compensation in the lamprey.
AB  - Vestibular compensation, i.e. recovery after unilateral labyrinthectomy (UL) in
      the lamprey (a lower vertebrate, Cyclostome), as well as different means of
      promoting the compensation, is described. UL results in a loss of equilibrium and
      rotation during swimming which is compensated in about 60 days. The deficit can,
      however, be immediately abolished by applying asymmetrical tonic visual or
      vestibular input (electrical stimulation of the optic or vestibular nerve,
      illumination of one eye, removal of one eye). In addition, asymmetrical visual
      input promotes plastic changes underlying the vestibular compensation. The
      compensation is discussed in relation to the neuronal network responsible for
      postural control in the lamprey and identified in our previous studies.

PMID- 8741773
TI  - Tobacco use and its contribution to early cancer mortality with a special
      emphasis on cigarette smoking.
AB  - This paper provides an overview of the relationship between tobacco use and early
      cancer mortality. It presents a retrospective examination of trends in smoking
      behavior and how these trends affected the national lung cancer mortality pattern
      during this century. Information on smoking prevalence is presented for black and
      white men and women for each 5-year birth cohort between 1885 and 1969. The
      author argues that the lung cancer mortality pattern observed in the United
      States since 1950 is entirely compatible with changes in smoking behavior among
      the various birth cohorts examined. The paper also reviews our current scientific
      knowledge about the etiological relationship between cigarette smoking and site
      specific cancer mortality, with particular emphasis on lung cancer. Data on other
      forms of tobacco use and cancer mortality risks are included as are data on
      environmental tobacco smoke exposures and nonsmokers' lung cancer risk. Data are
      presented to demonstrate that cigarette use alone will be responsible for nearly
      one-third of the U.S. cancer deaths expected in the United States in 1995, or
      168,000 premature cancer deaths. Among males, 38% of all cancer deaths are
      cigarette related, while among women 23% of all cancer deaths are due to
      cigarettes. These totals, however, include neither the cancer deaths that could
      reasonably be attributed to pipe, cigar, and smokeless tobacco use among males
      nor the estimated 3000 to 6000 environmental tobacco smoke-related lung cancer
      deaths that occur annually in nonsmokers. It is concluded that tobacco use,
      particularly the practice of cigarette smoking, is the single greatest cause of
      excess cancer mortality in U.S. populations.

PMID- 8741772
TI  - Sixth plot of the carcinogenic potency database: results of animal bioassays
      published in the General Literature 1989 to 1990 and by the National Toxicology
      Program 1990 to 1993.
AB  - This paper presents two types of information from the Carcinogenic Potency
      Database (CPDB): (a) the sixth chronological plot of analyses of long-term
      carcinogenesis bioassays, and (b) an index to chemicals in all six plots,
      including a summary compendium of positivity and potency for each chemical
      (Appendix 14). The five earlier plots of the CPDB have appeared in this journal,
      beginning in 1984 (1-5). Including the plot in this paper, the CPDB reports
      results of 5002 experiments on 1230 chemicals. This paper includes bioassay
      results published in the general literature between January 1989 and December
      1990, and in Technical Reports of the National Toxicology Program between January
      1990 and June 1993. Analyses are included on 17 chemicals tested in nonhuman
      primates by the Laboratory of Chemical Pharmacology, National Cancer Institute.
      This plot presents results of 531 long-term, chronic experiments of 182 test
      compounds and includes the same information about each experiment in the same
      plot format as the earlier papers: the species and strain of test animal, the
      route and duration of compound administration, dose level and other aspects of
      experimental protocol, histopathology and tumor incidence, TD50 (carcinogenic
      potency) and its statistical significance, dose response, author's opinion about
      carcinogenicity, and literature citation. We refer the reader to the 1984
      publications (1,6,7) for a detailed guide to the plot of the database, a complete
      description of the numerical index of carcinogenic potency, and a discussion of
      the sources of data, the rationale for the inclusion of particular experiments
      and particular target sites, and the conventions adopted in summarizing the
      literature. The six plots of the CPDB are to be used together since results of
      individual experiments that were published earlier are not repeated. Appendix 14
      is designed to facilitate access to results on all chemicals. References to the
      published papers that are the source of experimental data are reported in each of
      the published plots. For readers using the CPDB extensively, a combined plot is
      available of all results from the six separate plot papers, ordered
      alphabetically by chemical; the combined plot in printed form or on computer tape
      or diskette is available from the first author. A SAS database is also available.

PMID- 8741774
TI  - The changing epidemiology of smoking and lung cancer histology.
AB  - In 1950, the first large-scale epidemiological studies demonstrated that lung
      cancer is causatively associated with cigarette smoking, a finding subsequently
      confirmed by the Royal College of Physicians in London, the U.S. Surgeon General,
      and the World Health Organization. Although cigarette consumption has gradually
      decreased in the United States from a high of about 3800 cigarettes per adult per
      year in 1965 to about 2800 cigarettes in 1993, death from lung cancer has reached
      a high among males at the rate of 74.9/100,000/year and among females at the rate
      of 28.5. However, in the younger cohorts, the lung cancer death rate is
      decreasing in both men and women. In this overview we discuss the steeper
      increase during recent decades of lung adenocarcinoma incidence compared with
      squamous cell carcinoma of the lung. In 1950, the ratio of these two major types
      of lung cancer in males was about 1:18; today it is about 1:1.2-1.4. This
      overview discusses two concepts that are regarded as contributors to this change
      in the histological types of lung cancer. One factor is the decrease in average
      nicotine and tar delivery of cigarettes from about 2.7 and 38 mg in 1955 to 1.0
      and 13.5 mg in 1993, respectively. Other major factors for the reduced emission
      of smoke relate to changes in the composition of the cigarette tobacco blend and
      general acceptance of cigarettes with filter tips; the latter constitute 97% of
      all cigarettes currently sold. However, smokers of low-yield cigarettes
      compensate for the low delivery of nicotine by inhaling the smoke more deeply and
      by smoking more intensely; such smokers may be taking up to 5 puffs/min with puff
      volumes up to 55 ml. Under these conditions, the peripheral lung is exposed to
      increased amounts of smoke carcinogens that are suspected to lead to lung
      adenocarcinoma. Among the important changes in the composition of the tobacco
      blend of the U.S. cigarette is a significant increase in nitrate content (0.5% to
      1.2-1.5%), which raises the yields of nitrogen oxides and N-nitrosamines in the
      smoke. Furthermore, the more intense smoking by the consumers of low-yield
      cigarettes increases N-nitrosamines in the smoke 2- to 3-fold. Among the N
      nitrosamines is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a powerful
      lung carcinogen in animals that is exclusively formed from nicotine. This organ
      specific tobacco-specific nitrosamine (TSNA) induces adenocarcinoma of the lung.
      All of these factors, the more intense smoking, the deeper inhalation of the
      smoke, and the increased yields of N-nitrosamines in the smoke of low-yield
      cigarettes, are considered major contributors to the drastic increase in lung
      adenocarcinoma among cigarette smokers in recent years. This overview also
      discusses the differences in the major lung cancer types in female compared with
      male smokers as well as the likely underlying factors for increased lung cancer
      risk among African Americans compared with that among white Americans. Although
      the only sure way to prevent smoking-related diseases is giving up the tobacco
      habit, there must be a measure of protection for those who cannot accomplish
      this. Therefore, setting upper permissible limits of tar levels for the smoke of
      U.S. cigarettes, similar to strategies already taken in Western Europe, should be
      considered.

PMID- 8741775
TI  - Preventing tobacco-caused cancer: a call to action.
AB  - Nicotine addiction is the most common serious medical problem in the country.
      Tobacco use is responsible for 30% of cancer deaths in the United States and 90%
      of all lung cancer deaths. The physical addiction to nicotine explains why over
      30% of Americans continue to smoke or use tobacco despite their desires and
      efforts to quit. The testimony summarized in this paper recommends four broad
      strategies for preventing tobacco-caused cancers in the United States: a)
      mandating and reimbursing effective treatments for nicotine addiction; b)
      increasing Federal and state tobacco excise taxes and earmarking a fraction of
      tax revenues for tobacco prevention and cessation; c) enacting other policy
      changes to prevent tobacco use and addiction among children, including expanded
      clean indoor air legislation, comprehensive youth tobacco access legislation, and
      the regulation of tobacco products and their advertising and promotion; and d)
      expanding tobacco control research and critical Federal research support.
      Specific recommendations are given for each broad strategy.

PMID- 8741776
TI  - Alcohol as a cause of cancer.
AB  - This is a review of the epidemiologic literature on alcohol and risks of various
      cancers. Alcohol has consistently been related to risks of squamous cell
      carcinomas of the mouth, oral pharynx, larynx, and esophagus in multiple studies
      of varying design. The joint effects of alcohol and smoking are greater than
      additive, and are probably multiplicative, suggesting biological synergism. All
      major types of alcoholic beverages have been casually implicated in the genesis
      of these diseases. The influence of alcohol on risks of upper aerodigestive tract
      cancers may be greater in persons with marginal nutritional status than in better
      nourished individuals. Alcohol also has been associated with an increased risk of
      adenocarcinomas of the esophagus, gastro-esophageal junction, and gastric cardia,
      but the relationship is not as strong as for squamous cell esophageal carcinomas.
      Alcohol and tobacco account for over 80% of the squamous carcinomas of the mouth,
      pharynx, larynx, and esophagus in the United States. Risks of cancers of the
      distal stomach, pancreas, colon, and rectum have not been consistently related to
      alcohol, although possible relationships between beer drinking and rectal cancer
      and between heavy use of alcohol and pancreatic cancer warrant further study.
      Studies of alcohol and liver cancer, in which the confounding influence of
      hepatitis B was considered, have yielded inconsistent results and should be
      replicated. An association between heavy alcohol use and breast cancer has been
      observed in most studies, even after controlling for known risk factors for
      breast cancer, and additional investigations of this issue are warranted.

PMID- 8741777
TI  - Research and prevention priorities for alcohol carcinogenesis.
AB  - Research conducted during the last four decades has established that consumption
      of alcoholic beverages causes cancer. Etiologic research questions that remain
      relate to increases in risk at specific sites, the effects of various types of
      alcoholic beverages, the effect of various concentrations of alcohol, and the
      mechanism(s) of action, including possible interactions with other agents such as
      tobacco smoke. Prevention priorities for alcohol-related cancer depend on whether
      alcohol causes only the upper aerodigestive cancers or whether it also causes
      breast and possibly colon cancers. If alcohol causes aerodigestive cancers only,
      existing prevention programs to prevent alcohol abuse by heavy drinkers are
      sufficient. The possible small cancer risk faced by moderate drinkers may be more
      than offset by a decrease in the risk of cardiovascular death. On the other hand,
      if alcohol consumption increases the occurrence of breast cancer, a prevention
      program aimed at women who are at high risk for breast cancer is worth
      considering, but the risks must be weighed against the cardiovascular benefits
      for moderate drinkers.

PMID- 8741778
TI  - Diet, nutrition, and avoidable cancer.
AB  - In a 1981 review, Doll and Peto estimated that approximately 35% of cancer deaths
      in the United States were potentially avoidable by the modification of diet but
      that this percentage might be as low as 10% or as high as 70%. Since that time,
      the epidemiologic literature on diet and cancer has grown greatly, as has
      understanding of the mechanisms of carcinogenesis. In general, this expanded
      literature has not provided reason to alter the Doll and Peto estimate
      substantially. For colon cancer, evidence has accumulated that some of the
      international differences that were attributed to diet are probably due to
      physical activity. For breast cancer, the concept that fat intake per se is the
      primary reason for differences in rates among countries has not been supported by
      prospective studies. Although several lines of evidence suggest that caloric
      restriction and slow growth rates may contribute importantly to the low rates of
      breast cancer found outside Western countries, this may not translate directly to
      practical means of prevention. In contrast to breast cancer, more recent data
      have supported a causative role for red meat in the development of colon and
      prostate cancers, although perhaps not entirely due to its fat content. Whereas
      earlier thinking about nutrition and cancer emphasized the adverse effects of fat
      and other components in the diet, the most compelling evidence of the last decade
      has indicated the importance of protective factors, largely unidentified, in
      fruits and vegetables. Considering the more recent evidence, it is roughly
      estimated that about 32% of cancer may be avoidable by changes in diet; however,
      it now seems unlikely that less than 20% or more than 42% of cancer deaths would
      be avoidable by dietary change.

PMID- 8741779
TI  - Diet and cancer: future etiologic research.
AB  - In light of several credible diet and cancer hypotheses, we suggest strategies
      for advancing our understanding in this area. Two conceptual approaches can be
      taken in defining dietary exposure: the decompositional approach focuses on
      specific nutrients and other chemical constituents of food, whereas the
      integrative approach emphasizes the action of whole foods or food patterns
      (cuisines). Diet-cancer hypotheses can be organized according to this conceptual
      framework. We review four types of scientific investigation available to us for
      advancing the diet and cancer field: metabolic (clinical nutrition) studies;
      animal studies; observational epidemiologic investigations; and clinical trials.
      Each of these designs has its strengths and limitations. Observational
      epidemiologic studies and trials have the particular advantage of examining
      explicit cancer end points in humans. Results from metabolic and animal research,
      however, can complement the findings from epidemiologic studies and trials.
      Finally, we briefly review strategies for evaluating promising hypotheses linking
      diet to cancers of the large bowel, lung, breast, and prostate.

PMID- 8741780
TI  - Dietary modifiers of carcinogenesis.
AB  - Dietary components express a wide range of activities that can affect
      carcinogenesis. Naturally occurring substances in foods have been shown in
      laboratory experiments to serve as dietary antimutagens, either as
      bioantimutagens or as desmutagens. Dietary desmutagens may function as chemical
      inactivaters, enzymatic inducers, scavengers, or antioxidants. Dietary components
      may also act later in the carcinogenic process as tumor growth suppressors.
      Examples of dietary factors acting in each of these stages of carcinogenesis are
      presented, and potential anticarcinogens such as the carotenoids, tocopherols,
      phenolic compounds, glucosinolates, metal-binding proteins, phytoestrogens, and
      conjugated linoleic acid are discussed. Individual foods typically contain
      multiple potential anticarcinogens. Many of these substances can influence
      carcinogenesis through more than one mechanism. Some substances exhibit both
      anticarcinogenic and carcinogenic activity in vitro, depending on conditions.
      Epidemiologic research indicates that high fruit and vegetable consumption is
      associated with lower cancer risk. Little research has focused on the effects of
      single substances or single foods in man. Realization of the potential of
      foodborne substances to reduce the human burden of cancer will only be achieved
      with better measurement of dietary exposures and funding of multidisciplinary
      research in this area commensurate with its importance.

PMID- 8741781
TI  - Hormones and breast and endometrial cancers: preventive strategies and future
      research.
AB  - A number of hormonal approaches for prevention of endometrial and breast cancers
      have been proposed. Because of the hormonal responsiveness of both tumors, much
      attention has focused on effects of exogenous hormone use. Although estrogens in
      hormone replacement therapy increase the risk of endometrial cancer, the disease
      is substantially reduced by long-term use of oral contraceptives. The issues with
      breast cancer are more complex, mainly because of a variety of unresolved
      effects. Long-term estrogen use is associated with some increase in breast cancer
      risk, and certain patterns of oral contraceptives appear to predispose to early
      onset disease. With respect to estrogens, preventive approaches for both tumors
      would include use for as limited periods of time as possible. Addition of a
      progestin appears to lower estrogen-associated endometrial disease, but its
      effect on breast cancer risk remains less clear. Additional studies on effects of
      detailed usage parameters should provide useful insights into etiologic
      mechanisms. Other preventive approaches for endometrial cancer that may work
      through hormonal mechanisms include staying thin, being physically active, and
      maintaining a vegetarian diet. Breast cancer risk may possibly be reduced by
      extended periods of breastfeeding, restriction of intake of alcoholic beverages,
      remaining thin later in life, and being physically active. Additional research is
      needed to clarify the biologic mechanisms of these associations. The bridging of
      epidemiology with the biologic sciences should clarify many unresolved issues and
      lead to better preventive approaches.

PMID- 8741782
TI  - Nonhormonal drugs and cancer.
AB  - Nonhormonal drugs probably account for only a small proportion of human cancer
      but have contributed many valuable insights into carcinogenic mechanisms. The
      antineoplastics, radiopharmaceuticals, and a few other agents account for most of
      the known drug-induced cancer. A number of other agents are under suspicion,
      usually due to studies in laboratory animals or to preliminary clinical or
      epidemiologic observations. This group includes some drugs in widespread use such
      as clofibrate and cimetidine. For a few drugs that are carcinogenic in animals,
      such as dapsone and isoniazid, epidemiologic studies have shown little to no
      evidence of carcinogenicity. Recent experimental studies have shown tumor
      promotion by the commonly used antidepressants amitriptyline and fluoxetine and
      some antihistamines, which deserve epidemiologic investigation of cancer risk.
      Some drugs may also protect against cancer, as suggested by the lower risk of
      colorectal cancer among regular users of nonsteroidal antiinflammatory drugs.
      Pharmacoepidemiologic studies must take into account possible confounding by the
      original conditions for which drugs were taken and the typically long latency
      period of drug-induced cancer. Improved postmarketing surveillance, continued
      routine case-control surveillance, and ad hoc case-control and cohort studies are
      needed to evaluate drugs already in use as well as newly introduced agents.

PMID- 8741783
TI  - Overview of preventable industrial causes of occupational cancer.
AB  - This paper summarizes what is known about preventable causes of occupational
      cancer, including single agents, complex mixtures, and broad occupational
      associations. Epidemiologic methods have been very successful in documenting
      cancer risks associated with single agents. Epidemiologic data are most
      conclusive when an exposure-response relationship can be demonstrated. Examples
      of agents for which epidemiologic studies provide evidence of an exposure
      response relationship include benzene and (concurrent exposure to) ortho
      toluidine and aniline. Vinyl chloride and bischloromethyl ether are examples of
      associations between single agents and rare histologic types of cancer. It is
      more difficult to conduct epidemiologic studies to identify cancer risks
      associated with complex mixtures. Studies of diesel exhaust and lung cancer and
      metal machining oils are cited as having employed advanced industrial hygiene and
      epidemiologic methods for studies of complex mixtures. Elevated cancer risks have
      also been identified in broad occupational groups, including painters and dry
      cleaners. Epidemiologic case-control studies are often used to detect such
      associations but are limited in their abilities to detect the causal agents.
      Major gaps exist in knowledge of occupational cancer risks among women workers
      and workers of color. Because epidemiologic research measures illness and
      mortality that have already occurred, a positive study can be interpreted to
      represent a failure in prevention. The challenge we face in the next decade is to
      identify interventions earlier in the causal pathway (toxicologic testing,
      biomarkers of exposure or precancerous changes, institution of engineering and
      good industrial hygiene practices to reduce occupational exposure levels) so that
      occupational cancer can be prevented.

PMID- 8741784
TI  - Agricultural exposures and cancer.
AB  - The purpose of this report is to review the literature on cancer among persons
      employed in agriculture, to characterize the value of this line of research, and
      to recommend future directions. Farmers, despite a generally favorable mortality,
      appear to experience elevated rates for several cancers, including leukemia, non
      Hodgkin's lymphoma, multiple myeloma, soft-tissue sarcoma, and cancers of the
      skin, lip, stomach, brain, and prostate. The rates for several of these tumors
      (i.e., non-Hodgkin's lymphoma, multiple myeloma, skin, brain, and prostate)
      appear to be increasing in the general population. No set of established
      etiologic factors explains all the cancer excesses observed among farmers,
      although several are associated with naturally occurring or medically induced
      immunodeficiencies. This suggests that there may be factors in the agricultural
      environment that introduce immune system deficiencies. Farmers are exposed to a
      variety of substances that could operate through this mechanism, including
      pesticides, engine exhausts, solvents, dusts, and zoonotic microbes. Studies to
      further characterize the cancer risk among farmers, their dependents, and farm
      laborers, and to identify the exposures that may be involved would not only be
      useful in providing a safe work environment in agriculture but may furnish
      considerable insight into the causes for a number of tumors that are rising in
      incidence in the general population.

PMID- 8741785
TI  - Future etiologic research in occupational cancer.
AB  - Research focused on occupational exposure has been one of the cornerstones of
      epidemiological research into the etiology of cancer. It is appropriate to
      critically assess the contribution of this research effort and to assess the
      potential for making significant progress in the future in unraveling the
      etiology of cancer by studying the occupational environment. The study of the
      occupational environment has indeed been very fruitful. It is likely that there
      remain many more carcinogens to be discovered, but we have not deployed
      adequately sensitive study methods. The two major obstacles to quality research
      have been inadequate exposure assessment and insufficient sample sizes. Quality
      exposure assessment requires the participation of trained experts (industrial
      hygienists, chemists, etc.); it also requires an adequate information base on the
      exposures that occur in different workplaces. We need structures and career paths
      that facilitate the participation of exposure experts in epidemiological
      research. We need active large-scale industrial hygiene surveys to better
      characterize the U.S. workplace. This will be useful for epidemiological studies
      and for public health purposes. Community-based case-control studies will need to
      be much larger than they have been traditionally, with 1000 as a minimum number
      of cases and controls.

PMID- 8741786
TI  - The importance of information dissemination in the prevention of occupational
      cancer.
AB  - It is assumed that prevention of occupational cancer depends upon dissemination
      of research findings, resulting in changes in work processes and reduction of
      occupational exposures to carcinogens. Examples of successes and failures of
      information dissemination are found in the results of research on silicosis.
      Better assessment of the effectiveness of information dissemination is needed,
      along with greater understanding of the barriers to implementation of the
      information by workers and management and improved hazard surveillance.

PMID- 8741787
TI  - Lung cancer and air pollution.
AB  - Epidemiologic studies over the last 40 years suggest rather consistently that
      general ambient air pollution, chiefly due to the incomplete combustion of fossil
      fuels, may be responsible for increased rates of lung cancer. This evidence
      derives from studies of lung cancer trends, studies of occupational groups,
      comparisons of urban and rural populations, and case-control and cohort studies
      using diverse exposure metrics. Recent prospective cohort studies observed 30 to
      50% increases in lung cancer rates associated with exposure to respirable
      particles. While these data reflect the effects of exposures in past decades, and
      despite some progress in reducing air pollution, large numbers of people in the
      United States continue to be exposed to pollutant mixtures containing known or
      suspected carcinogens. It is not known how many people in the United States are
      exposed to levels of fine respirable particles that have been associated with
      lung cancer in recent epidemiologic studies. These observations suggest that the
      most widely cited estimates of the proportional contribution of air pollution to
      lung cancer occurrence in the United States based largely on the results of
      animal studies, may be too low. It is important that better epidemiologic
      research be conducted to allow improved estimates of lung cancer risk from air
      pollution among the general population. The development and application of new
      epidemiologic methods, particularly the improved characterization of population
      wide exposure to mixtures of air pollutants and the improved design of ecologic
      studies, could improve our ability to measure accurately the magnitude of excess
      cancer associated with air pollution.

PMID- 8741788
TI  - Drinking water and cancer.
AB  - Any and all chemicals generated by human activity can and will find their way
      into water supplies. The types and quantities of carcinogens present in drinking
      water at the point of consumption will differ depending on whether they result
      from contamination of the source water, arise as a consequence of treatment
      processes, or enter as the water is conveyed to the user. Source-water
      contaminants of concern include arsenic, asbestos, radon, agricultural chemicals,
      and hazardous waste. Of these, the strongest evidence for a cancer risk involves
      arsenic, which is linked to cancers of the liver, lung, bladder, and kidney. The
      use of chlorine for water treatment to reduce the risk of infectious disease may
      account for a substantial portion of the cancer risk associated with drinking
      water. The by-products of chlorination are associated with increased risk of
      bladder and rectal cancer, possibly accounting for 5000 cases of bladder cancer
      and 8000 cases of rectal cancer per year in the United States. Fluoridation of
      water has received great scrutiny but appears to pose little or no cancer risk.
      Further research is needed to identify and quantify risks posed by contaminants
      from drinking-water distribution pipes, linings, joints, and fixtures and by
      biologically active micropollutants, such as microbial agents. We need more cost
      effective methods for monitoring drinking-water quality and further research on
      interventions to minimize cancer risks from drinking water.

PMID- 8741789
TI  - Molecular epidemiology and prevention of cancer.
AB  - Preventable environmental causes of cancer, including tobacco smoke and other
      carcinogens in the diet, workplace, and ambient environment are responsible for
      the vast majority of human cancers. This paper reviews recent molecular
      epidemiologic studies that have focused on environmental carcinogenesis and
      environment-host interactions. Biomarkers such as carcinogen-DNA and carcinogen
      protein adducts, mutations in reporter or target genes (e.g., HPRT, GPA, ras,
      p53), or genetic or acquired susceptibility factors (e.g., polymorphisms in the
      P450 or glutathione-S-transferase genes and serum levels of antioxidants) have
      shown significant potential in prevention. They should be useful in early
      identification of at risk individuals and in designing and monitoring
      interventions (smoking cessation, exposure reduction, and chemoprevention).

PMID- 8741790
TI  - Cancer prevention strategies: use of cancer prevention research registries.
AB  - We present a model to plan a rational strategy for cancer prevention that has two
      main functions--assessment and intervention. The assessment function includes
      three main components: to identify populations at high cancer risk, which may be
      due to their ethnic group, occupational and environmental exposures, family
      history, cigarette smoking, or other risk factors; to assess exposure to known
      carcinogens through the general and occupational environments, lifestyle factors,
      and the home as well as to document known carcinogens using human tissue banks
      and develop and validate questionnaires to target known risk factors for each of
      the most common cancers; and to conduct research studies of high-risk
      populations, including studies on mechanism and genetic testing. The intervention
      function includes three components: development of population-based intervention
      programs using the results from the research studies; evaluation of intervention
      programs; and modification of existing intervention programs and implementation
      of new ones. The above-proposed prevention strategy depends to a great extent on
      population-based cancer registries. Existing cancer registries around the United
      States should be strengthened and other dimensions should be added to their
      charge to augment their function in prevention research. To convert existing
      population-based cancer registries, particularly those that serve multiethnic and
      multicultural populations, into Cancer Prevention Research Registries (CPRRs),
      three types of data in addition to their existing required data complement should
      be incorporated. These are exposure information including occupational history,
      host factors information, and information about family history of cancer and
      associated conditions. The primary goal of the CPRRs should be to support cancer
      prevention research in its widest sense. Future research needs must be designed
      to investigate each of the components of the prevention strategy as well as its
      integrated performance. Regardless of what we do in the future, we must now
      promote healthier lifestyles, prevent exposure to known carcinogens, and improve
      early detection procedures.

PMID- 8741791
TI  - Ionizing radiation and cancer prevention.
AB  - Ionizing radiation long has been recognized as a cause of cancer. Among
      environmental cancer risks, radiation is unique in the variety of organs and
      tissues that it can affect. Numerous epidemiological studies with good dosimetry
      provide the basis for cancer risk estimation, including quantitative information
      derived from observed dose-response relationships. The amount of cancer
      attributable to ionizing radiation is difficult to estimate, but numbers such as
      1 to 3% have been suggested. Some radiation-induced cancers attributable to
      naturally occurring exposures, such as cosmic and terrestrial radiation, are not
      preventable. The major natural radiation exposure, radon, can often be reduced,
      especially in the home, but not entirely eliminated. Medical use of radiation
      constitutes the other main category of exposure; because of the importance of its
      benefits to one's health, the appropriate prevention strategy is to simply work
      to minimize exposures.

PMID- 8741792
TI  - Ionizing radiation: future etiologic research and preventive strategies.
AB  - Estimates of cancer risks following exposure to ionizing radiation traditionally
      have been based on the experience of populations exposed to substantial (and
      known) doses delivered over short periods of time. Examples include survivors of
      the atomic bombings at Hiroshima and Nagasaki, and persons treated with radiation
      for benign or malignant disease. Continued follow-up of these populations is
      important to determine the long-term effects of exposure in childhood, to
      characterize temporal patterns of excess risk for different types of cancer, and
      to understand better the interactions between radiation and other host and
      environmental factors. Most population exposure to radiation occurs at very low
      dose rates. For low linear energy transfer (LET) radiations, it often has been
      assumed that cancer risks per unit dose are lower following protracted exposure
      than following acute exposure. Studies of nuclear workers chronically exposed
      over a working lifetime provide data that can be used to test this hypothesis,
      and preliminary indications are that the risks per unit dose for most cancers
      other than leukemia are similar to those for acute exposure. However, these
      results are subject to considerable uncertainty, and further information on this
      question is needed. Residential radon is the major source of population exposure
      to high-LET radiation. Current estimates of the risk of lung cancer due to
      residential exposure to radon and radon daughters are based on the experience of
      miners exposed to much higher concentrations. Data indicate that lung cancer risk
      among miners is inversely associated with exposure rate, and also is influenced
      by the presence of other lung carcinogens such as arsenic in the mine
      environment. Further study of populations of radon-exposed miners would be
      informative, particularly those exposed at below-average levels. More direct
      evidence on the effects of residential exposure to radon also is desirable but
      might be difficult to come by, as risks associated with radon levels found in
      most homes might be too low to be quantified accurately in epidemiological
      studies.

PMID- 8741793
TI  - Overview of ultraviolet radiation and cancer: what is the link? How are we doing?
AB  - Sun exposure has now been established as the most important avoidable cause of
      nonmelanoma skin cancer (NMSC) and melanoma. With specific reference to melanoma,
      there are several key issues that remain to be resolved. These include definition
      of the action spectrum, the importance of systemic effects of sun exposure,
      whether a tan is protective, the risk of tanning booth exposures, and the
      efficacy of sunscreens. Also the role, if any, of sun exposure in noncutaneous
      malignancies remains to be established. Melanoma incidence and mortality have
      increased dramatically over the past several decades, but these increases have
      now slowed, and for mortality among those 15 to 45 years of age, decreasing rates
      are now observed. Improving the coverage of the Surveillance, Epidemiology, and
      End Results (SEER) registries by requiring pathology laboratories in non-SEER
      areas to report cancers among SEER area residents will allow correct
      interpretation of these trends in the future at minimal cost. The available data
      on trends in NMSC incidence and mortality are suboptimal but suggest a pattern of
      declining mortality despite increasing incidence. Trends in NMSC morbidity have
      not been defined. Establishing NMSC registries in a few diverse sentinel areas
      would allow more reliable inference and monitoring. Techniques are being
      developed for reducing sun exposures and increasing early detection of skin
      cancers in the general population, but improved monitoring of incidence,
      mortality, and morbidity is required to monitor the effects of current and future
      ozone depletion and to evaluate prevention and early detection measures.

PMID- 8741794
TI  - Preventive strategies and research for ultraviolet-associated cancer.
AB  - Ultraviolet (UV)-associated cancer is the most common cancer in the United
      States. Approximately 90% of nonmelanoma skin cancer and 65% of melanoma are
      attributable to UV exposure and theoretically could be eliminated by primary
      prevention measures. Safe sun strategy includes use of sunscreens, use of
      protective clothing, minimization of exposure from 10 A.M. to 3 P.M., and
      avoidance of tanning parlors. Although more definitive data in human populations
      on the effectiveness of sunscreens to prevent melanoma and skin cancer are
      needed, sunscreens are thought to reduce risk. Safe sun prevention must start in
      childhood and adolescence when people receive most of their UV exposure.
      Secondary prevention through professional and public education and early
      detection may further reduce melanoma mortality.

PMID- 8741795
TI  - Overview: viral agents and cancer.
AB  - Substantial evidence indicates that several common viruses are clearly or
      probable causal factors in the etiology of specific malignancies. These viruses
      either normally establish latency or can become persistent infections.
      Oncogenesis is probably linked to an enhanced level of viral activation in the
      infected host, reflecting heavy viral dose or compromised immune control. The
      major virus-malignancy systems include hepatitis B virus (HBV), hepatitis C virus
      (HCV), and hepatocellular carcinoma; human lymphotropic virus-type 1 (HTLV-1) and
      adult T-cell leukemia/lymphoma (ATL); Epstein-Barr virus (EBV) and endemic
      Burkitt's lymphoma, nasopharyngeal carcinoma, and Hodgkin's disease; and human
      papilloma virus (HPV) and cervical cancer. Of these, a vaccine is available only
      for HBV. These malignancies tend to occur in early to mid-life and account for a
      substantial amount of morbidity and person-years lost. They are also likely to
      occur as "opportunistic malignancies" among individuals infected with human
      immunodeficiency virus type-1, particularly among those who experience prolonged
      survival.

PMID- 8741797
TI  - Viruses and human cancers: challenges for preventive strategies.
AB  - Virus-associated human cancers provide unique opportunities for preventive
      strategies. The role of human papilloma viruses (HPV 16 and 18), hepatitis B
      virus (HBV), Epstein-Barr herpes virus (EBV), and retroviruses (human
      immunodeficiency virus [HIV] and human T-cell leukemia/lymphoma virus [HTLV]) in
      the development of common carcinomas and lymphomas represents a major cancer
      threat, particularly among individuals residing in developing countries, which
      account for 80% of the world's population. Even though these viruses are not the
      sole etiological agents of these cancers (as would be the case for infectious
      diseases), different approaches can be implemented to significantly decrease the
      incidence of virus-associated malignancies. The first approach is vaccination,
      which is available for HBV and possibly soon for EBV. The long delay between
      primary viral infection and development of associated tumors as well as the cost
      involved with administering vaccinations detracts from the feasibility of such an
      approach within developing countries. The second approach is to increase efforts
      to detect pre-cancerous lesions or early tumors using immunovirological means.
      This would allow early diagnosis and better treatment. The third strategy is
      linked to the existence of disease susceptibility genes, and suggests that
      counseling be provided for individuals carrying these genes to encourage them to
      modify their lifestyles and other conditions associated with increased cancer
      risks (predictive oncology). Specific recommendations include: a) increase
      international studies that explore the causes of the large variations in
      prevalence of common cancers throughout the world; b) conduct interdisciplinary
      studies involving laboratory investigation and social sciences, which may suggest
      hypotheses that may then be tested experimentally; and c) promote more preventive
      and health enhancement strategies in addition to curative and replacement
      therapies.

PMID- 8741796
TI  - Bacterial infection as a cause of cancer.
AB  - Bacterial infections traditionally have not been considered major causes of
      cancer. Recently, however, bacteria have been linked to cancer by two mechanisms:
      induction of chronic inflammation and production of carcinogenic bacterial
      metabolites. The most specific example of the inflammatory mechanism of
      carcinogenesis is Helicobacter pylori infection. H. pylori has been
      epidemiologically linked to adenocarcinoma of the distal stomach by its
      propensity to cause lifelong inflammation. This inflammation is in turn thought
      to cause cancer by inducing cell proliferation and production of mutagenic free
      radicals and N-nitroso compounds. H. pylori is the first bacterium to be termed a
      definite cause of cancer in humans by the International Agency for Research on
      Cancer. Mutagenic bacterial metabolites are also suspected to increase risk for
      cancer. This model is best exemplified in colon cancer. Bile salt metabolites
      increase colonic cell proliferation. Exogenous compounds such as rutin may be
      metabolized into mutagens by resident colonic flora. Moreover, Bacteroides
      species can produce fecapentaenes, potent in vitro mutagens, in relatively high
      concentrations. In vivo data on human carcinogenesis by bacterial metabolites,
      however, are inconsistent. Local bacterial infections may also predispose to
      nonnodal lymphomas, although the mechanisms for this are unknown. Gastric
      lymphomas and immunoproliferative small intestinal disease have been most
      strongly linked to underlying bacterial infection. Because bacterial infections
      can be cured with antibiotics, identification of bacterial causes of malignancy
      could have important implications for cancer prevention.

PMID- 8741798
TI  - Differences in cancer incidence, mortality, and survival between African
      Americans and whites.
AB  - This report highlights selected evidence of different cancer patterns among
      African Americans and whites and considers potential risk factors associated with
      these cancers. During the years 1987 to 1991, African Americans experienced
      higher incidence and mortality rates than whites for multiple myeloma and for
      cancers of the oropharynx, colorectum, lung and bronchus, cervix, and prostate.
      African Americans had lower incidence and mortality for cancer of the urinary
      bladder. The incidence of breast cancer was higher among white women, but
      mortality was higher among African American women. Five-year relative survival
      for the period 1983 to 1990 was generally lower among African Americans than
      whites for cancers of the oropharynx, colorectum, cervix, prostate, and female
      breast but slightly higher for multiple myeloma. From 1973 to 1991, there were
      significant declines in cervical cancer incidence among women of both races,
      oropharyngeal cancer mortality among whites, and bladder cancer mortality for
      whites and African Americans. Risk factors for the more prominent cancers suggest
      that efforts aimed at changing lifestyles, achieving socioeconomic parity, and
      insuring environmental equity are likely to relieve African Americans of much of
      their disproportionate cancer burden.

PMID- 8741799
TI  - Racial, ethnic, and gender variations in cancer risk: considerations for future
      epidemiologic research.
AB  - There is no question that the risk of many cancers varies substantially by race,
      ethnic group, and gender. Although important clues to cancer etiology may come
      from investigating the differences in risk across subgroups of the population,
      epidemiologic research has often focused on white men. More descriptive and
      analytic studies are needed to identify and explain variations in risk among
      population subgroups. Especially important are studies to clarify the role of
      differential exposures, susceptibility, and diagnostic factors in cancer
      incidence, although differences in treatment may contribute to variations in
      cancer mortality. Improvements in classification of ethnicity, assessment of
      carcinogenic exposures in various subpopulations, and measures of host
      susceptibility states should augment future epidemiologic research designed to
      better understand mechanisms underlying the racial, ethnic, and gender
      differences in cancer risk.

PMID- 8741800
TI  - Targeting Hispanic populations: future research and prevention strategies.
AB  - Minority populations face a wide variety of economic, institutional, and cultural
      barriers to health care. These barriers and low levels of education and income
      pose significant challenges for health professionals in developing cancer
      research and prevention-control strategies. It is suggested that specific
      segments of Hispanic populations fit the model of an underdeveloped country in
      the intermediate stage of epidemiological transition. Since noncommunicable
      diseases have not yet fully emerged in some of these Hispanic population
      segments, the opportunity exists to apply primordial prevention strategies. Such
      campaigns would focus on dissuading members of these populations from adopting
      negative health behaviors while promoting positive lifestyle choices. Optimal
      programs would increase cancer screening participation and discourage risk
      behaviors through community-oriented, population-based interventions. Future
      directions in prevention and control efforts for minority populations should
      include expanded health insurance coverage, improved access to health care,
      greater emphasis on minority recruitment in health care fields, focused
      epidemiologic and clinical research, and identification and replication of
      effective components within existing prevention-control programs.

PMID- 8741802
TI  - Identification and management of inherited cancer susceptibility.
AB  - Identification of inherited cancer-predisposing genes offers opportunities for
      cancer prevention. Inherited susceptibility genes have been identified, primarily
      through studies of unusual cancer cases and families but also through general
      population studies. Examples include the RB1 gene for retinoblastoma; the WT1
      gene for Wilms' tumor; germline p53 mutations in families with the Li-Fraumeni
      syndrome; the NF1 and NF2 genes for neuroblastomatosis, types 1 and 2; the VHL
      gene for renal cancer and other tumors associated with Von Hippel-Lindau disease;
      the APC gene for adenomatous polyposis coli; the BRCA1 gene for hereditary breast
      and ovarian cancer; and the mismatch repair genes for colon and other common
      cancers. For some cancers, identification of gene carriers might be beneficial
      for targeting screening and chemopreventive interventions. On the other hand,
      predisposition testing for cancer has the potential for harm from loss of
      insurability and employability, psychological distress, social stigmatization and
      other adverse effects. Research is needed to identify predisposition testing
      procedures that maximize benefits while minimizing harm to subjects.
      Chemoprevention trials in genetically susceptible populations offer the prospect
      of finding effective methods of reducing future cancer risk.

PMID- 8741801
TI  - Using biomarkers of genetic susceptibility to enhance the study of cancer
      etiology.
AB  - There has been increasing interest in the interaction of genetic susceptibility
      and xenobiotic exposures in cancer etiology. Study of gene-environment
      interactions may increase our ability to characterize relatively low population
      risks if a substantial proportion of the population cancer burden is attributed
      to high risk among a smaller group of genetically susceptible members. Further,
      these studies may provide insight into the mechanism of carcinogenesis, which can
      help establish the biologic plausibility of an exposure-cancer relationship.
      Biologic processes important in tumorigenesis that exhibit substantial
      interindividual differences may function as susceptibility factors. Potential
      examples include polymorphic enzymes, which activate and detoxify procarcinogens
      and carcinogens (e.g., certain P450 enzymes, N-acetyltransferase [NAT2],
      glutathione S-transferase M1), and variation in the capacity to repair DNA.
      Biologic assays are now available to evaluate many of these functions at the DNA
      and phenotype level and can be readily incorporated into studies of cancer
      etiology.

PMID- 8741803
TI  - Estimating avoidable causes of cancer.
AB  - Evidence that much cancer is preventable derives from observations of time trends
      and geographic patterns of cancer, birth cohort changes, high risks in groups
      with well-defined exposures, and experimental studies. In an effort to identify
      additional opportunities for reducing the impact of cancer on society, this
      conference assessed avoidable causes of cancer. The magnitude and extent of
      preventable causes of cancer are subjects of intense debate, with discrepancies
      often related to the use of different time frames and different weights for
      epidemiologic and toxicologic evidence. There is much agreement, however, about
      the exposures that increase risk, notably tobacco, alcohol, diet, radiation,
      medications, occupational exposures, general environmental exposures, and
      infectious agents. Interactions between carcinogenic exposures and genetic
      susceptibility are also important. Concerted efforts are needed to identify
      avoidable causes of cancer and to apply knowledge already obtained to reduce the
      cancer burden.

PMID- 8741804
TI  - Controlling the avoidable causes of cancer: needs and opportunities for etiologic
      research.
AB  - This meeting of the President's Cancer Panel was designed to provide an overview
      of known and suspect causes of cancer and to indicate those that might be
      considered avoidable. Two complex concepts are inherent in this charge: cause and
      avoidability. Risk factors for cancer are designated as causal when the evidence
      from observational and laboratory research is judged sufficient in relation to
      criteria for causality; the extent to which cancers of specific sites can be
      avoided is best estimated by the attributable risk statistic, which incorporates
      both the exposure pattern and the relative risk for the cancer-causing agent. A
      research agenda on avoidable causes of cancer should then address both the risks
      associated with the agents that cause cancer and the pattern of exposure to the
      agents. Presentations at the meeting highlighted gaps in the evidence on the
      risks associated with various known and potential causes of cancer and on the
      patterns of exposure across the diverse groups within the population. In spite of
      these gaps, presenters emphasized that the evidence is already sufficient to
      justify intervention for many agents and that action need not be delayed for the
      well-characterized causes of cancer. In addition to research recommendations
      offered by presenters for specific causal agents, the scientific basis for cancer
      prevention might be generally strengthened by new research strategies directed at
      developing new tools for exposure assessment, for investigating the risks of
      mixtures, and for population surveillance.

PMID- 8741805
TI  - Primary prevention of cancer: needs and opportunities for research.
AB  - Strategies for cancer prevention generally come from observational epidemiology
      and must include monitoring for the effects of the actions. The measurement
      iterative loop allows us to refine our approach to cancer prevention. When
      available, clinical trials can also provide strategies for control. Exposure
      specific strategies are described; these are such things as health promotion and
      behavior modification, legislative approaches, treatment for addiction, changes
      in the food supply, chemoprevention, occupational and environmental regulation,
      immunization, identification of persons with enhanced genetic susceptibility, and
      improved surveillance systems. For some exposures such as tobacco, zero exposure
      is the goal. For others, prudent avoidance or exposures as low as reasonably
      achievable are appropriate approaches. Research on how to impact deeply ingrained
      lifestyle and cultural factors has high priority.

PMID- 8741806
TI  - Cancer among special populations: women, ethnic minorities, and the poor.
AB  - The study of cancer among women, ethnic minorities, and the poor can yield useful
      information about etiology and lead to effective recommendations for prevention.
      Opportunities exist for affecting cancer rates among women by studying and
      altering hormonal exposures and, possibly, alcohol consumption. The study of diet
      among ethnic groups may be more informative than among populations with
      homogeneous diets. The gender and racial differences among lung cancer patients
      related to tobacco need further research. Innovative multidisciplinary research
      is needed to reduce the ethnic, gender, and institutional barriers to ensure
      success in the fight against cancer.

PMID- 8741807
TI  - Diabetic medicine: the southbound migration continues.

PMID- 8741808
TI  - R.D. Lawrence and the formation of the Diabetic Association.
AB  - The history of the (British) Diabetic Association is bound up with the life of Dr
      R.D. Lawrence, its co-founder and first Chairman. Thus the story begins with a
      review of his early life and experience. He himself committed some memories to
      paper, in autobiographical context, to which he gave the title A Splendid Life,
      and this review draws freely on those unpublished notes, with the permission of
      his sons. Unfortunately, many records, letters and documents were destroyed when
      the flat of his secretary, the late Miss Lilian Pearce, was damaged by the 1987
      hurricane storms, and later vandalized while she was in hospital. Academically
      brilliant, with his heart set on becoming a surgeon, Robin Lawrence was diagnosed
      as having diabetes in 1920, at the age of 28. The poor prognosis lead him to set
      up practice in Florence, where he could at least enjoy the splendours of Italian
      culture. His health deteriorated badly during the winter of 1922, but alerted to
      the introduction of insulin therapy by Dr. G.A. Harrison, he returned to King's
      College Hospital, London and received his first injection of insulin on 31 May
      1923. Thereafter, he devoted his life to the understanding of the disease, and
      the welfare of those affected by it. Together with his patient, the author and
      scientist H.G. Wells, Robin Lawrence was responsible for the formation of the
      Diabetic Association, the first patient-oriented association to be established in
      the United Kingdom. Historical data are taken from early issues of the Diabetic
      Journal and minutes of meetings to which the author has been given access.

PMID- 8741809
TI  - The relationship between cow's milk exposure and type 1 diabetes.
AB  - Environmental factors are important for the development of Type 1 diabetes
      mellitus. They likely account for changes in the incidence of this disease over
      time, as well as the well-documented differences in incidence in ethnically and
      genetically similar people living in different parts of the world. There is a
      relationship between early cow's milk exposure and the development of Type 1
      diabetes in humans, and between early cow's milk exposure and the development of
      autoimmune diabetes in rodent models of Type 1 diabetes. Moreover, some
      immunological studies have suggested a possible mechanism whereby exposure to
      cow's milk protein could result in beta-cell directed autoimmunity and subsequent
      Type 1 diabetes. Although provocative, the existence of alternative explanations
      for these epidemiological and biological observations, suggest that the data are
      insufficient to conclude that the observed associations represent causal
      relationships or to mandate changes in recommendations for infant feeding. The
      question of whether or not avoidance of cow's milk protein in infancy will
      prevent Type 1 diabetes can, however, be tested in an international randomized
      clinical trial of infant diets, which is currently under review.

PMID- 8741810
TI  - Insulin resistance: a multifaceted metabolic syndrome. Insights gained using a
      low-dose insulin infusion technique.
AB  - The term 'insulin resistance', when applied to human disease, is often equated
      with impaired whole-body insulin-mediated glucose disposal as determined using
      techniques such as the hyperinsulinaemic glucose 'clamp' technique. Insulin
      resistance may be defined in more generic terms as 'a state in which normal
      concentrations of insulin produce an attenuated biological response'--a
      definition which does not restrict consideration of insulin action to a solitary
      aspect of metabolism and emphasizes the importance of examining the effects of
      insulin at concentrations which are relevant to normal physiology. While a number
      of useful investigative techniques have been developed for the assessment of
      insulin action in man, most focus narrowly on glucose metabolism; other key
      aspects of metabolism have received far less attention. Moreover, the
      pharmacological hyperinsulinaemia usually attained during euglycaemic clamp
      studies is unsuitable for assessing processes such as adipocyte lipolysis which
      are maximally inhibited by insulin concentrations within the low-physiological
      range. In this article we present a summary of our investigations of insulin
      action in vivo using a low-dose incremental insulin infusion technique. This
      technique permits examination of circulating insulin/metabolite dose-response
      relationships within the lower physiological range of plasma insulin
      concentrations. Using this approach, we have identified multiple abnormalities in
      the regulation of carbohydrate and lipid metabolism in subjects with a diverse
      array of insulin-resistant states characterized by variable degrees of glucose
      intolerance. Of note are the consistent observations of defective regulation of
      non-esterified fatty acid and glycerol metabolism, being apparent even in
      patients in whom glucose tolerance was either normal or only marginally impaired.
      Our studies indicate that defective insulin action is not confined to impaired
      glucose disposal in insulin-resistant disorders and is usually evident in other
      aspects of intermediary metabolism. We suggest that the concept of insulin
      resistance as a pathological entity would be usefully enhanced by greater
      recognition of the multiple defects in insulin action which may be encountered in
      insulin-resistant states.

PMID- 8741811
TI  - Effects of insulin on body composition in patients with insulin-dependent and non
      insulin-dependent diabetes.
AB  - Insulin is used to control blood glucose but may have an adverse effect on the
      amount and distribution of fat mass and other cardiovascular risk factors. To
      test this hypothesis the effect of insulin therapy on blood glucose, body
      composition, and lipid levels was measured during 6 months in 9 patients with
      newly diagnosed insulin-dependent (Type 1) diabetes mellitus (IDDM) and 15
      patients with non-insulin dependent (Type 2) diabetes (NIDDM) and secondary
      failure of therapy with oral hypoglycaemic agents. Both groups received similar
      daily doses of insulin (approximately 0.6 units kg-1 day-1). Glycaemic control
      improved during 6 months treatment in both groups, although the reduction in
      HbA1c was greater in IDDM (5.2 +/- 0.7%) than in NIDDM (2.0 +/- 0.4%, p < 0.001).
      All parameters of the lipid profile improved in IDDM but not in NIDDM. Body
      weight, lean mass, and fat mass, measured by dual energy x-ray absorptiometry,
      increased at 1 month in IDDM but not in NIDDM. By 6 months, body weight had
      increased more in IDDM than NIDDM (9.1 +/- 1.2 vs 3.77 +/- 0.5 kg, p < 0.01). The
      increase in weight was predominantly lean mass in IDDM (60.4 +/- 9.3%) and fat
      mass in NIDDM (59.9 +/- 8.4%). The increase in lean mass was greater in IDDM than
      NIDDM (5.6 +/- 1.1 vs 1.4 +/- 0.3 kg, p < 0.001). Fat mass increased by similar
      increments in IDDM and NIDDM (3.4 +/- 0.8 vs 2.4 +/- 0.5 kg, p = ns) and was
      predominantly an increase in trunk fat (IDDM: 2.3 +/- 0.6 kg, NIDDM: 2.0 +/- 0.4
      kg, p = ns). The central/peripheral fat mass ratio prior to treatment was lower
      in IDDM than NIDDM (0.64 +/- 0.05 vs 1.09 +/- 0.09, p < 0.01) and then increased
      in IDDM by 0.32 +/- 0.15 (p = 0.07) and in NIDDM by 0.22 +/- 0.06 (p < 0.001). In
      conclusion, insulin therapy is associated with weight gain in both IDDM and
      NIDDM. In the former, weight gain reflects increases in lean mass whereas in
      NIDDM it reflects an increase in trunk fat mass. It remains to be determined
      whether this trend to central obesity partly offsets other benefits of insulin
      therapy in NIDDM.

PMID- 8741812
TI  - Pre-meal insulin analogue insulin lispro vs Humulin R insulin treatment in young
      subjects with type 1 diabetes.
AB  - The present prospective one-year randomized study was conducted to compare
      soluble human insulin, with a new rapid-acting human insulin analogue, lispro,
      with respect to postprandial glucose excursions, frequency of hypoglycaemic
      episodes, glucose control, and long-term safety in 39 subjects (20 females, 19
      males) with Type 1 diabetes. The duration of diabetes, gender distribution, and
      age were similar in the two groups. The total number of hypoglycaemic episodes
      was significantly less (p < 0.04, Wilcoxon rank sum test) in subjects receiving
      insulin lispro compared with regular human insulin over the 12-month period. The
      2-h postprandial glucose excursion at 1 year was also significantly less (p <
      0.05, ANOVA) in the group treated with insulin lispro. The reductions in the
      total number of hypoglycaemic episodes and in the postprandial glucose excursion
      with use of insulin lispro may be beneficial for the long-term management of
      subjects with Type 1 diabetes. However, the greatest benefit identified by the
      subjects receiving insulin lispro was the greater convenience of the rapid-acting
      analogue.

PMID- 8741813
TI  - Elevated erythrocyte sodium-lithium countertransport activity correlates with
      increased intracellular sodium and free calcium-ion concentration in type 2
      diabetes.
AB  - To explore the mechanism by which elevated sodium-lithium countertransport
      activity (SLC) associates with both predisposition to hypertension and diabetic
      nephropathy, we investigated the interrelationships among SLC, intracellular
      sodium concentration ([Na]i), intracellular free calcium-ion concentration
      ([Ca2+]i), diabetic nephropathy, hypertension, family history of hypertension,
      and other factors in 48 patients with Type 2 diabetes and 24 healthy controls.
      There was a significant correlation between SLC and [Na]i (r = 0.36, p < 0.05),
      [Na]i and [Ca2+]i (r = 0.47, p < 0.01), SLC and [Ca2+]i (r = 0.46, p < 0.01), and
      between HbA1c and [Ca2+]i (r = 0.38, p < 0.01). Both [Na]i and [Ca2+]i were
      significantly higher in the patients with elevated SLC than in those with normal
      SLC (p < 0.01 and p < 0.05, respectively). In stepwise multivariate regresssion
      analysis, [Na]i, HbA1c, and SLC appeared as independent determinants of [Ca2+]i.
      These data suggest a significant correlation of elevated SLC with increased [Na]i
      and [Ca2+]i. This may be a possible mechanism underlying the close association of
      elevated SLC with both predisposition to hypertension and diabetic nephropathy.

PMID- 8741814
TI  - Plasminogen activator inhibitor (PAI-1) activity is elevated in Asian and
      Caucasian subjects with non-insulin-dependent (type 2) diabetes but not in those
      with impaired glucose tolerance (IGT) or non-diabetic Asians.
AB  - In order to study the plasminogen activator inhibitor activity (PAI-1) in
      subjects at different risk of non-insulin-dependent diabetes and ischaemic heart
      disease we examined 89 subjects with diet controlled NIDDM (49 Caucasian, 40
      Asian), 29 with impaired glucose tolerance (IGT) (13 Caucasian, 16 Asian), and
      149 with normal glucose tolerance (67 Caucasian, 82 Asian). Diabetes was
      diagnosed by WHO criteria and highly specific, monoclonal antibody-based assays
      were used to measure insulin, intact proinsulin, and des 31,32 proinsulin.
      Subjects with NIDDM were significantly more obese, had more central distribution
      of obesity, higher fasting plasma specific insulin concentrations (NIDDM median
      74 pmol l-1 vs IGT 41 pmol l-1, p < 0.01 and vs normals 34 pmol l-1, p < 0.001)
      and higher PAI-1 activity than normals and those with IGT (NIDDM 23.0 +/- 6.9 vs
      IGT 16.8 +/- 5.0, p < 0.001 and vs normals 17.1 +/- 6.9 AU ml-1, p < 0.001).
      However, PAI-1 activity was not significantly different between Asian and
      Caucasian normals (17.5 +/- 7.3 vs 16.5 +/- 6.4 AU ml-1, p = ns) and diabetic
      (22.8 +/- 7.3 vs 23.1 +/- 6.6 AU ml-1, p = ns) subjects. In addition to
      relationships with obesity and plasma triglyceride, PAI-1 activity, after
      controlling for age, sex, body mass index, and waist-hip ratio, was related to
      fasting insulin (partial r = 0.22, p < 0.001), intact proinsulin (partial r =
      0.36, p < 0.001), and des 31,32 proinsulin concentrations (partial r = 0.33, p <
      0.001) as measured by highly specific assays. The association of PAI-1 with
      diabetes was weakened but remained statistically significant (p = 0.042) after
      controlling for age, sex, ethnicity, obesity, plasma triglyceride, and all
      insulin-like molecules. We conclude that, although PAI-1 activity is raised in
      subjects with diet-treated NIDDM, it is normal in subjects with IGT and non
      diabetic Asians, populations at high risk of NIDDM and ischaemic heart disease.
      Raised PAI-1 activity may play an important role in the pathogenesis of
      macrovascular disease in subjects with NIDDM, but is unlikely to explain excess
      risk of ischaemic heart disease in Asians and those with impaired glucose
      tolerance.

PMID- 8741815
TI  - Prospective assessment of autonomic and peripheral nerve function in adolescents
      with diabetes.
AB  - Autonomic and peripheral nerve function were studied prospectively in 102
      adolescents with Type 1 diabetes over a 5-year period. All adolescents were
      assessed three times; 54 were assessed four times. The median age at baseline was
      14.5 (range 10.4-18.0) yr. The median diabetes duration at baseline was 6.8
      (range 1.3-15.2) yr. Autonomic nerve function was assessed by measuring heart
      rate variation during deep breathing, valsalva manoeuvre, standing from a lying
      position (30/15 ratio), and the postural change in systolic blood pressure.
      Peripheral nerve function was assessed by determining the thermal threshold for
      heat and cold at the wrist and foot and the vibration threshold at the great toe
      and medial malleolus. At baseline, 29.5% adolescents had at least one abnormal
      autonomic nerve test and 28.4% had at least one abnormal peripheral nerve test.
      There was no significant increase in the number of abnormalities over the study
      period. Persisting abnormalities were present in only six individuals.
      Abnormalities were not related to age, diabetes duration or glycaemic control. In
      summary, a low rate of neurological abnormalities was found, suggesting that more
      than 3 years of follow-up is required to detect evolving neuropathy in this age
      group.

PMID- 8741816
TI  - The relationships between cardiovascular risk factors and socio-economic status
      in people with diabetes.
AB  - The hypothesis that the prevalence of cardiovascular risk factors in people with
      diabetes is inversely related to socio-economic status was tested. Demographic
      and biochemical data were collected on 1246 patients, aged 20-69 years, attending
      a hospital diabetes clinic. This is estimated to represent between 71% and 78% of
      all people of this age with a diagnosis of diabetes in the health authority. In
      total, 296 people were classified as Type 1 (insulin-dependent) diabetic patients
      (age of onset < 31, now on insulin). Using data from the 1991 census a
      deprivation score was ascribed to each individual according to their area
      (enumeration district) of residence. The total study population was ranked by
      deprivation score and divided into quintiles. The relationships between means and
      quintiles of deprivation were assessed by ANOVA for linear trend, and between
      proportions and quintiles of deprivation by the chi-squared test for trend. In
      Type 1 diabetes increasing quintiles of deprivation were significantly related to
      mean serum cholesterol (p < 0.01) and proportion smoking (p < 0.01), and in Type
      2 (non-insulin-dependent) diabetes to mean body mass index (p < 0.001),
      proportion smoking (p < 0.001), and proportion with proteinuria (p < 0.05). The
      need for health measures to prevent cardiovascular disease in people with
      diabetes is greatest in deprived areas.

PMID- 8741817
TI  - The prognostic value of blood glucose in diabetic patients with acute myocardial
      infarction.
AB  - The aim of the study was to investigate prospectively the prognostic value of
      blood glucose on admission in diabetic and non-diabetic patients with an acute
      myocardial infarction. Three hundred and thirty-three diabetic and 565 non
      diabetic patients were admitted with acute myocardial infarction during the study
      period of 3.5 years. There was a significant association between mortality and
      blood glucose on admission in diabetic patients (regression coefficient, r =
      0.92, 0.5 < p < 0.02) but not in non-diabetic individuals (r = 0.69, 0.2 < p <
      0.5). Age- and sex-standardized mortality was higher in the diabetic group (12.2%
      vs 7.4%, p < 0.03), but was identical if standardized also for blood glucose on
      admission. We conclude that a high blood glucose on admission is a bad prognostic
      indicator in a diabetic patient with an acute myocardial infarction. The excess
      mortality in diabetic patients with acute myocardial infarction can be attributed
      to the higher proportion with hyperglycaemia.

PMID- 8741818
TI  - Erectile dysfunction in men with and without diabetes mellitus: a comparative
      study.
AB  - The aetiology of erectile dysfunction in men with diabetes remains unclear and is
      likely to be multifactorial. To explore clinical factors of possible aetiological
      relevance, 59 men with diabetes and erectile dysfunction (ED), referred to a
      sexual problem clinic, were compared with an age-matched group of non-diabetic
      clinic attenders with ED. Sexual interest was both higher and correlated
      negatively with age in the diabetic groups. There were differences in the sexual
      problems experienced by partners in the two groups. Both groups had received
      nocturnal penile tumescence (NPT) monitoring and the majority had received
      intracavernosal injections of PGE1 to assess capacity for erectile response.
      Twenty-nine percent of the diabetic men had satisfactory NPT, and most of these
      had other evidence of psychogenic causation. The men with diabetes were more
      likely to have a satisfactory response to intracavernosal injections of PGE1, and
      this was particularly the case among those with impaired NPTs. This difference
      requires explanation and may be of aetiological relevance.

PMID- 8741819
TI  - Outcome of pregnancy in patients with insulin-dependent diabetes mellitus and
      nephropathy with moderate renal impairment.
AB  - This study examines the effect of pregnancy on fetal outcome and maternal renal
      function in 17 women with Type 1 diabetes mellitus and nephropathy attending a
      joint diabetic-antenatal clinic between 1985 and 1993. There were 7 successful
      pregnancies in 6 women with moderate renal impairment, mean pre-pregnancy serum
      creatinine 165 mumol l-1 (Group 1), and 12 in 11 women with proteinuria and
      preserved renal function (Group 2). Median gestation of pregnancy was 31 + 3
      weeks in Group 1 and 36 + 4 weeks in Group 2 (p < 0.05). All babies in Group 1
      required neonatal intensive care for a median of 19 days (range 8-271) as
      compared to only 5 of 13 in Group 2 whose median stay was 13 (7-17) days (p <
      0.05). There was one late death in Group 1. Longitudinal creatinine data in those
      with moderate renal impairment suggest no systematic adverse long-term effect of
      pregnancy on maternal renal function, although differing changes in renal
      function were observed during pregnancy. The generally favourable outcome
      achieved relied heavily upon neonatal care expertise.

PMID- 8741820
TI  - Physical development in Estonian children with type 1 diabetes.
AB  - This cross-sectional study describes the physical development of 62 diabetic
      patients who comprised one-third of all 10-17-year-old Estonian children with
      Type 1 diabetes. Diabetic children were shorter than healthy Estonian children
      with a mean corrected height standard deviation score (SDS) of -0.78 +/- 1.37.
      Diabetic children living in rural areas were significantly shorter than urban
      diabetic children (p < 0.05). A significant negative correlation was found
      between the duration of diabetes and the corrected height SDS (p < 0.01; r = 
      0.36). Current glycated haemoglobin (HbA1) (mean 11.7 +/- 2.2%) was inversely
      correlated to insulin dosage (p = 0.01) and to availability of home blood glucose
      monitoring (p = 0.03). Stepwise regression analysis showed that duration of
      diabetes (p = 0.02) and urban or rural abode (p = 0.04), but not age at onset of
      diabetes current HbA1 level, availability of home blood glucose monitoring or
      socio-economic status, influenced significantly corrected height standard
      deviation score (SDS). Despite having the same body mass index, diabetic
      children, especially girls, had thicker biceps and triceps skinfolds than
      controls. Estonian teenage diabetic children were shorter than healthy children
      and had increased biceps and triceps skinfold thickness without being overweight.
      Duration of disease was the predominant adverse influence on growth.

PMID- 8741821
TI  - The epidemiology of diabetic foot problems.

PMID- 8741822
TI  - The pathogenesis of diabetic foot problems: an overview.

PMID- 8741823
TI  - Biomechanical aspects of diabetic foot disease: aetiology, treatment, and
      prevention.

PMID- 8741824
TI  - Early atherogenesis in diabetes mellitus.

PMID- 8741825
TI  - Microvascular aspects of diabetic foot disease.

PMID- 8741826
TI  - The histology of diabetic foot ulcers.

PMID- 8741827
TI  - Diagnosis and management of diabetic peripheral neuropathy.

PMID- 8741828
TI  - The use of non-invasive vascular assessment in diabetic patients with foot
      lesions.

PMID- 8741829
TI  - Lower extremity arterial reconstruction in patients with diabetes mellitus.

PMID- 8741830
TI  - Antibiotic therapy in diabetic foot infection.

PMID- 8741831
TI  - The Charcot joint in diabetes.

PMID- 8741832
TI  - The clinical examination of the diabetic foot in daily practise.

PMID- 8741833
TI  - A healed ulcer: what now?

PMID- 8741834
TI  - Education and the diabetic foot.

PMID- 8741835
TI  - Mutational analysis of capping protein function in Saccharomyces cerevisiae.
AB  - To investigate physiologic functions and structural correlates for actin capping
      protein (CP), we analyzed site-directed mutations in CAP1 and CAP2, which encode
      the alpha and beta subunits of CP in Saccharomyces cerevisiae. Mutations in four
      different regions caused a loss of CP function in vivo despite the presence of
      mutant protein in the cells. Mutations in three regions caused a complete loss of
      all aspects of function, including the actin distribution, viability with sac6,
      and localization of CP to actin cortical patches. Mutation of the fourth region
      led to partial loss of only one function-formation of actin cables. Some
      mutations retained function and exhibited the complete wild-type phenotype, and
      some mutations led to a complete loss of protein and therefore loss of function.
      The simplest hypothesis that can explain these results is that a single
      biochemical property is necessary for all in vivo functions. This biochemical
      property is most likely binding to actin filaments, because the nonfunctional
      mutant CPs no longer co-localize with actin filaments in vivo and because direct
      binding of CP to actin filaments has been well established by studies with
      purified proteins in vitro. More complex hypotheses, involving the existence of
      additional biochemical properties important for function, cannot be excluded by
      this analysis.

PMID- 8741836
TI  - Antagonistic effects of signal transduction by intracellular and extracellular
      cAMP on gene regulation in Dictyostelium.
AB  - In Dictyostelium, cAMP plays a role as an intracellular second messenger and in
      addition, as an extracellular first messenger. Both functions are thought to be
      tightly linked because adenylyl cyclase is coupled via G-proteins to the cell
      surface cAMP receptor cAR 1. Using the discoidin I gene family as a molecular
      marker for the first stages of development, we show here that induction of
      transcription requires the G-protein subunit alpha 2 and thus an as yet
      unidentified surface receptor, CRAC (cytosolic regulator of adenylyl cyclase),
      and PKA. Induction can be conferred by an increase in intracellular cAMP. In
      contrast, transcriptional down-regulation occurs by stimulation of cAR 1 with
      extracellular cAMP and a subsequent, G-protein-independent Ca2+ influx. In a G
      alpha 2 gene disruption mutant, discoidin I expression can be efficiently
      modulated by analogues simulating intracellular cAMP (discoidin induction) and
      extracellular cAMP (discoidin down-regulation). We thus demonstrate possible
      antagonistic functions of intra- and extracellular cAMP.

PMID- 8741837
TI  - TOR controls translation initiation and early G1 progression in yeast.
AB  - Saccharomyces cerevisiae cells treated with the immunosuppressant rapamycin or
      depleted for the targets of rapamycin TOR1 and TOR2 arrest growth in the early G1
      phase of the cell cycle. Loss of TOR function also causes an early inhibition of
      translation initiation and induces several other physiological changes
      characteristic of starved cells entering stationary phase (G0). A G1 cyclin mRNA
      whose translational control is altered by substitution of the UBI4 5' leader
      region (UBI4 is normally translated under starvation conditions) suppresses the
      rapamycin-induced G1 arrest and confers starvation sensitivity. These results
      suggest that the block in translation initiation is a direct consequence of loss
      of TOR function and the cause of the G1 arrest. We propose that the TORs, two
      related phosphatidylinositol kinase homologues, are part of a novel signaling
      pathway that activates eIF-4E-dependent protein synthesis and, thereby, G1
      progression in response to nutrient availability. Such a pathway may constitute a
      checkpoint that prevents early G1 progression and growth in the absence of
      nutrients.

PMID- 8741838
TI  - A replication-enhancing element with transcriptional silencer activity in
      autonomously replicating human chromosomal fragments.
AB  - We have identified specific nucleotide sequences involved in autonomous
      replication of human chromosomal fragments in human cells. Nested deletion
      analysis of a 10.2-kb long human chromosomal fragment showed that replication
      efficiency of the fragment was reduced to about 50% by loss of a short specific
      segment. Deletions outside the segment reduced the replication efficiency
      depending on their lengths. By introducing linker substitutions, we found that
      the distinct segment required for the efficient replication consisted of an 18-bp
      sequence, named REE1 (Replication Enhancing Element 1). Single or tandem copies
      of REE1 alone had no significant replication activity, but they stimulated
      replication of human chromosomal DNA fragments. We found, in addition, that the
      REE1 sequence inserted at a site 2.7 kb upstream of the SV40 early promoter
      caused repression of transcription from the promoter, suggesting that REE1 had a
      transcriptional silencer activity. Introduction of linker substitutions into the
      REE1 indicated that the nucleotide sequences required for the repression of
      transcription were the same as those for enhancement of replication. Thus, REE1
      is responsible for both enhancement of replication and repression of
      transcription.

PMID- 8741839
TI  - Isolation and characterization of p19INK4d, a p16-related inhibitor specific to
      CDK6 and CDK4.
AB  - Cyclin-dependent kinases 4 and 6 are complexed with many small cellular proteins
      in vivo. We have isolated cDNA sequences, INK4d, encoding a 19-kDa protein that
      is associated with CDK6 in several hematopoietic cell lines. p19 shares equal
      similarity and a common ancestor with other identified inhibitors of the p16/INK4
      family. p19 interacts with and inhibits the activity of both CDK4 and CDK6 and
      exhibits no detectable interaction with the other known CDKs. p19 protein is
      present in both cell nuclei and cytoplasm. The p19 gene has been mapped to
      chromosome 19p13.2, and the level of its mRNA expression varies widely between
      different tissues. In contrast to p21 and p27 whose interaction with CDK subunits
      is dependent on or stimulated by the cyclin subunit, the interaction of p19 and
      p18 with CDK6 is hindered by the cyclin protein. Binary cyclin D1-p18/p19 or
      cyclin D1-CDK6 complexes are highly stable and cannot be dissociated by excess
      amounts of cyclin D1 or p19/p18 proteins, suggesting that p16 inhibitors and D
      cyclins may interact with CDKs 4 and 6 in a competing or potentially mutually
      exclusive manner.

PMID- 8741840
TI  - Identification of seven rat axonemal dynein heavy chain genes: expression during
      ciliated cell differentiation.
AB  - Axonemal dyneins are molecular motors that drive the beating of cilia and
      flagella. We report here the identification and partial cloning of seven unique
      axonemal dynein heavy chains from rat tracheal epithelial (RTE) cells.
      Combinations of axonemal-specific and degenerate primers to conserved regions
      around the catalytic site of dynein heavy chains were used to obtain cDNA
      fragments of rat dynein heavy chains. Southern analysis indicates that these are
      single copy genes, with one possible exception, and Northern analysis of RNA from
      RTE cells shows a transcript of approximately 15 kb for each gene. Expression of
      these genes was restricted to tissues containing axonemes (trachea, testis, and
      brain). A time course analysis during ciliated cell differentiation of RTE cells
      in culture demonstrated that the expression of axonemal dynein heavy chains
      correlated with the development of ciliated cells, while cytoplasmic dynein heavy
      chain expression remained constant. In addition, factors that regulate the
      development of ciliated cells in culture regulated the expression of axonemal
      dynein heavy chains in a parallel fashion. These are the first mammalian dynein
      heavy chain genes shown to be expressed specifically in axonemal tissues.
      Identification of the mechanisms that regulate the cell-specific expression of
      these axonemal dynein heavy chains will further our understanding of the process
      of ciliated cell differentiation.

PMID- 8741841
TI  - Inositol transport in Saccharomyces cerevisiae is regulated by transcriptional
      and degradative endocytic mechanisms during the growth cycle that are distinct
      from inositol-induced regulation.
AB  - Regulation of inositol uptake activity in Saccharomyces cerevisiae during the
      growth cycle was examined. Activity increased as the cell population transited
      from lag phase to exponential growth, and continued to increase until late
      exponential phase. The increase in activity was due to increased transcription of
      the ITR1 gene and synthesis of the Itr1 permease. When the culture reached
      stationary phase, uptake activity decreased and dropped to a minimum within 4 h.
      The decrease was due to repression of ITR1 transcription, independent of the
      negative regulator Opi1p, and degradation of the existing permease. Degradation
      depended on delivery of the permease to the vacuole through the END3/END4
      endocytic pathway. During exponential growth in inositol-containing medium the
      permease is also rapidly degraded, whereas in inositol-free medium the permease
      is highly stable. Rapid degradation of the permease at stationary phase occurred
      in inositol-free medium, indicating that there are two distinct mechanisms that
      trigger endocytosis and degradation in response to different physiological
      stimuli. In addition, the level of the enzyme required for inositol biosynthesis,
      inositol-1-phosphate synthase, encoded by INO1, is not reduced in stationary
      phase cells, and this contrast in the regulation of inositol supply is discussed.

PMID- 8741842
TI  - The Ydj1 molecular chaperone facilitates formation of active p60v-src in yeast.
AB  - Molecular chaperones have been implicated in the formation of active p60v-src
      tyrosine kinase. In Saccharomyces cerevisiae, expression of p60v-src causes cell
      death, a phenomenon that requires functional Hsp90. We show here that mutations
      in a member of a second class of chaperones, the yeast dnaJ homologue YDJ1,
      suppress the lethality caused by p60v-src. One p60v-src-resistant ydj1 mutant,
      ydj1-39, which has two point mutations in the highly conserved "J" domain, has
      reduced levels of v-src mRNA and protein. However, a ydj1 null mutant produces
      normal quantities of active p60v-src, indicating that Ydj1p facilitates, but is
      not essential for, the formation of active p60v-src. We also report p60v-src
      resistance in a previously identified temperature-sensitive ydj1 mutant, ydj1
      151. In this mutant, the level of p60v-src remains unaltered, but the protein is
      much less active in vivo. In addition, p60v-src immunoprecipitates from the ydj1
      151 strain contained Hsp90 and Hsp70 in greater amounts than in wild-type
      strains. Ydj1 protein was also detected in p60v-src immunoprecipitates from both
      wild-type and ydj1-151 strains. These results indicate that Ydj1p participates in
      the formation of active p60v-src via molecular chaperone complexes.

PMID- 8741843
TI  - Cytoskeletal integrity is required throughout the mitogen stimulation phase of
      the cell cycle and mediates the anchorage-dependent expression of cyclin D1.
AB  - The proliferation of many nontransformed cells depends on cell adhesion. We
      report here that disrupting the cytoskeleton in normal human fibroblasts causes
      the same cell cycle phenotype that is observed after blocking cell adhesion:
      suspended cells and cytochalasin D-treated monolayers fail to progress through G1
      despite normal mitogen-induced expression of c-myc mRNA. Midway between G0 and
      the beginning of S-phase, cell cycle progression becomes independent of adhesion
      and the cytoskeleton. At this stage, the cells are also mitogen independent.
      Molecular analyses showed that Rb hyperphosphorylation and the induction of
      cyclin D1 occur slightly earlier than the transition to cytoskeleton
      independence. Moreover, these molecular events are blocked by cytochalasin D.
      Overall, our data indicate the following: 1) anchorage and cytoskeletal integrity
      are required throughout the mitogen-dependent part of G1; 2) mitogens and the
      cytoskeleton jointly regulate the phosphorylation of Rb; and 3) this
      interdependence is manifest in the regulation of cyclin D1.

PMID- 8741844
TI  - Modulation of myosin filament organization by C-protein family members.
AB  - We have analyzed the interactions between two types of sarcomeric proteins:
      myosin heavy chain (MyHC) and members of an abundant thick filament-associated
      protein family (myosin-binding protein; MyBP). Previous work has demonstrated
      that when MyHC is transiently transfected into mammalian nonmuscle COS cells, the
      expressed protein forms spindle-shaped structures consisting of bundles of myosin
      thick filaments. Co-expression of MyHC and MyBP-C or -H modulates the MyHC
      structures, resulting in dramatically longer cables consisting of myosin and MyBP
      encircling the nucleus. Immunoelectron microscopy indicates that these cable
      structures are more uniform in diameter than the spindle structures consisting
      solely of MyHC, and that the myosin filaments are compacted in the presence of
      MyBP. Deletion analysis of MyBP-H indicates that cable formation is dependent on
      the carboxy terminal 24 amino acids. Neither the MyHC spindles nor the MyHC/MyBP
      cables associate with the endogenous actin cytoskeleton of the COS cell. While
      there is no apparent co-localization between these structures and the microtubule
      network, colchicine treatment of the cells promotes the formation of longer
      assemblages, suggesting that cytoskeletal architecture may physically impede or
      regulate polymer formation/extension. The data presented here contribute to a
      greater understanding of the interactions between the MyBP family and MyHC, and
      provide additional evidence for functional homology between MyBP-C and MyBP-H.

PMID- 8741846
TI  - Identification of a ligand-binding site in an immunoglobulin fold domain of the
      Saccharomyces cerevisiae adhesion protein alpha-agglutinin.
AB  - The Saccharomyces cerevisiae adhesion protein alpha-agglutinin (Ag alpha 1p) is
      expressed by alpha cells and binds to the complementary a-agglutinin expressed by
      a cells. The N-terminal half of alpha-agglutinin is sufficient for ligand binding
      and has been proposed to contain an immunoglobulin (Ig) fold domain. Based on a
      structural homology model for this domain and a previously identified critical
      residue (His292), we made Ag alpha 1p mutations in three discontinuous patches of
      the domain that are predicted to be in close proximity to His292 in the model.
      Residues in each of the three patches were identified that are important for
      activity and therefore define a putative ligand binding site, whereas mutations
      in distant loops had no effect on activity. This putative binding site is on a
      different surface of the Ig fold than the defined binding sites of
      immunoglobulins and other members of the Ig superfamily. Comparison of protein
      interaction sites by structural and mutational analysis has indicated that the
      area of surface contact is larger than the functional binding site identified by
      mutagenesis. The putative alpha-agglutinin binding site is therefore likely to
      identify residues that contribute to the functional binding site within a larger
      area that contacts a-agglutinin.

PMID- 8741845
TI  - Resorption-cycle-dependent polarization of mRNAs for different subunits of V
      ATPase in bone-resorbing osteoclasts.
AB  - Protein sorting in eukaryotic cells is mainly done by specific targeting of
      polypeptides. The present evidence from oocytes, neurons, and some other
      polarized cells suggests that protein sorting can be further facilitated by
      concentrating mRNAs to their corresponding subcellular areas. However, very
      little is known about the mechanism(s) involved in mRNA targeting, or how
      widespread and dynamic such mRNA sorting might be. In this study, we have used an
      in vitro cell culture system, where large multinucleated osteoclasts undergo
      continuous structural and functional changes from polarized (resorbing) to a
      nonpolarized (resting) stage. We demonstrate here, using a nonradioactive in situ
      hybridization technique and confocal microscopy, that mRNAs for several vacuolar
      H(+)-ATPase subunits change their localization and polarity in osteoclasts
      according to the resorption cycle, whereas mRNA for cytoplasmic carbonic
      anhydrase II is found diffusely located throughout the osteoclast during the
      whole resorption cycle. Antisense RNA against the 16-kDa or 60-kDa V-ATPase
      subunit inhibits polarization of the osteoclasts, as determined by cytoskeleton
      staining. Antisense RNA against carbonic anhydrase II, however, has no such
      effect.

PMID- 8741849
TI  - The roles of engrailed.

PMID- 8741847
TI  - The paramyxovirus simian virus 5 hemagglutinin-neuraminidase glycoprotein, but
      not the fusion glycoprotein, is internalized via coated pits and enters the
      endocytic pathway.
AB  - The hemagglutinin-neuraminidase (HN) and fusion (F) glycoproteins of the
      paramyxovirus simian virus 5 (SV5) are expressed on the surface of virus-infected
      cells. Although the F protein was found to be expressed stably, the HN protein
      was internalized from the plasma membrane. HN protein lacks known internalization
      signals in its cytoplasmic domain that are common to many integral membrane
      proteins that are internalized via clathrin-coated pits. Thus, the cellular
      pathway of HN protein internalization was examined. Biochemical analysis
      indicated that HN was lost from the cell surface with a t1/2 of approximately 45
      50 min and turned over with a t1/2 of approximately 2 h. Immunofluorescent
      analysis showed internalized SV5 HN in vesicle-like structures in a juxtanuclear
      pattern coincident with the localization of ovalbumin. In contrast the SV5 F
      glycoprotein and the HN glycoprotein of the highly related parainfluenza virus 3
      (hPIV-3) were found only on the cell surface. Immunogold staining of HN on the
      surface of SV5-infected CV-1 cells and examination using electron microscopy,
      showed heavy surface labeling that gradually decreased with time. Concomitantly,
      gold particles were detected in the endosomal system and with increasing time,
      gold-labeled structures having the morphology of lysosomes were observed. On the
      plasma membrane approximately 5% of the gold-labeled HN was found in coated pits.
      The inhibition of the pinching-off of coated pits from the plasma membrane by
      cytosol acidification significantly reduced HN internalization. Internalized HN
      was co-localized with gold-conjugated transferrin, a marker for the early
      endosomal compartments, and with gold-conjugated bovine serum albumin, a marker
      for late endosomal compartments. Taken together, these data strongly suggest that
      the HN glycoprotein is internalized via clathrin-coated pits and delivered to the
      endocytic pathway.

PMID- 8741850
TI  - Viruses as pacemakers in the evolution of defence mechanisms against cancer.

PMID- 8741851
TI  - RNA editing, introns and evolution.

PMID- 8741852
TI  - Rapid identification of transgenic zebrafish.

PMID- 8741848
TI  - Nucleolar accumulation of poly (A)+ RNA in heat-shocked yeast cells: implication
      of nucleolar involvement in mRNA transport.
AB  - Transport of mRNA from the nucleus to the cytoplasm plays an important role in
      gene expression in eukaryotic cells. In wild-type Schizosaccharomyces pombe cells
      poly(A)+ RNA is uniformly distributed throughout the nucleoplasm and cytoplasm.
      However, we found that a severe heat shock blocks mRNA transport in S. pombe,
      resulting in the accumulation of bulk poly(A)+ RNA, as well as a specific intron
      less transcript, in the nucleoli. Pretreatment of cells with a mild heat shock,
      which induces heat shock proteins, before a severe heat shock protects the mRNA
      transport machinery and allows mRNA transport to proceed unimpeded. In heat
      shocked S. pombe cells, the nucleolar region condensed into a few compact
      structures. Interestingly, poly(A)+ RNA accumulated predominantly in the
      condensed nucleolar regions of the heat-shocked cells. These data suggest that
      the yeast nucleolus may play a role in mRNA transport in addition to its roles in
      rRNA synthesis and preribosome assembly.

PMID- 8741853
TI  - Production of full-length cDNA from a picornaviral genome by RT-PCR.

PMID- 8741854
TI  - Generation of overlapping open reading frames.

PMID- 8741855
TI  - Engrailed, Wnt and Pax genes regulate midbrain--hindbrain development.
AB  - The mouse Engrailed, Wnt and Pax genes, which are homologues of Drosophila
      segmentation genes, have provided a critical genetic entry point for dissecting
      the molecular and cellular control of mesencephalon and metencephalon development
      in vertebrates. Mutant phenotypes and gene expression data suggest that six
      members of these gene families are required for early formation of these brain
      regions. Ectopic transplantation studies have shown that the midbrain-hindbrain
      junction protein can act as an organizer and recruit certain host cells to re
      establish parts of the entire region. Taken together, these studies indicate that
      the mesencephalon and metencephalon develop as one independent unit, and that the
      genetic network regulating development of this region involves conserved genes
      that control segmentation in Drosophila. By analogy, segmentation of the rest of
      the brain might best be described in terms of 'genetic units' defined by genetic
      and transplantation data.

PMID- 8741856
TI  - Exchanging partners: recombination in E. coli.
AB  - Examination of the many proteins involved in recombination in Escherichia coli
      has provided detailed information concerning how homologous DNA is paired and
      exchanged between different molecules. Recent studies have begun to resolve long
      standing issues, such as how a DNA helicase with rampant nuclease activity is
      able to promote the initiation of recombination, how the four-stranded
      intermediate arising from DNA strand exchange is migrated and resolved and how
      ancillary proteins assist RecA protein-mediated activities. In addition, the
      identification of eukaryotic homologues of RecA protein, similar both in
      structure and in function, shows that at least some of the fundamental steps of
      recombination have been conserved in all organisms. This finding holds promise
      that the development of in vitro systems for recombination by eukaryotic proteins
      lies in the not-too-distant future.

PMID- 8741857
TI  - Programmed DNA deletions in Tetrahymena: mechanisms and implications.
AB  - Ciliated protozoa carry out remarkable DNA rearrangements during nuclear
      differentiation, including precise deletion of thousands of specific DNA
      fragments from their somatic genomes. Recent molecular studies on DNA deletion in
      Tetrahymena have revealed two interesting sets of cis-acting regulatory
      sequences, one determines the general regions to be deleted and the other the
      precise end points of deletion. This information suggested a novel mechanism of
      DNA rearrangement and raised interesting questions regarding its evolutionary
      origin. It is speculated that this process might be related to the unique genetic
      property of ciliate macronuclei, which transcribe actively and divide without
      chromosome condensation.

PMID- 8741858
TI  - Determination of cell fate in Bacillus subtilis.
AB  - On starvation, the soil bacterium Bacillus subtilis stops dividing and initiates
      sporulation, a simple developmental process involving the differentiation of two
      cell types. Sporulation begins with a reorganization of the cell cycle, to
      produce cells with the size and chromosome content appropriate for the
      developmental process. The central division that would normally occur, to produce
      a pair of identical daughter cells, is blocked and the cell divides
      asymmetrically to produce a small, polar prespore cell and a much larger mother
      cell. The developmental fates of the two cells are dictated by the localized
      activation of cell-specific transcription factors, which are controlled by
      mechanisms that respond to the cellular asymmetry.

PMID- 8741859
TI  - Sequence alignment through pictures.

PMID- 8741860
TI  - Plant chromosomes unite.

PMID- 8741861
TI  - An excellent bag of nerves.

PMID- 8741862
TI  - Anomalies of the nipple: an additional finding in CHARGE syndrome.

PMID- 8741863
TI  - Twins and twinning.

PMID- 8741864
TI  - X-inactivation patterns in monozygotic and dizygotic female twins.
AB  - We have tested the hypothesis that contrasting X-inactivation patterns could be a
      trigger for monozygotic twinning in females. X-inactivation patterns were studied
      in umbilical cord tissue in 43 monozygotic twin pairs and 24 dizygotic twin
      pairs. Very skewed or non-random X-inactivation patterns were observed in both
      twins in six of the monozygotic twin pairs and in one of the dizygotic twin
      pairs. Contrasting X-inactivation patterns occurred in only one of the six
      monozygotic twin pairs. This does not support the original hypothesis. There is a
      trend to extreme skewing of X-inactivation pattern occurring more frequently in
      monozygotic twins.

PMID- 8741865
TI  - X-chromosome inactivation is mostly random in placental tissues of female
      monozygotic twins and triplets.
AB  - Patterns of X-chromosome inactivation in chorion, amnion, and cord from 79 pairs
      of twins were examined. Seven sets of triplets were included in the analysis,
      both as twin pairs and triplets. Twins were stratified as dizygotic (DZ),
      monozygotic (MZ), monochorionic, and dichorionic and were selected for birth
      weight discordance, discordance for congenital anomalies, twin-twin transfusion
      syndrome, and various patterns of vascular anastomosis. X-inactivation was
      predominantly symmetric. Chorion was the most likely tissue to show asymmetric X
      inactivation and was found most frequently in MZ dichorionic twins. There was no
      correlation of X-inactivation pattern with the selected clinical criteria. This
      study does not confirm that asymmetric X-inactivation in embryonic tissues is a
      common phenomenon in female twins, including monozygotic twins.

PMID- 8741866
TI  - Some causes of genotypic and phenotypic discordance in monozygotic twin pairs.
AB  - The use of the adjective "identical" rather than monozygotic leads to
      misunderstandings about the biology of monozygotic twinning. Most monozygotic
      twin pairs are not identical; there may be major discordance for birth weight,
      genetic disease, and congenital anomalies. These indicate that postzygotic events
      may lead to the formation of two or more cell clones in the inner cell mass and
      early embryo that actually stimulate the monozygotic twinning event. There is
      also evidence that there may be unequal allocation of numbers of cells to the
      monozygotic twins; this may have widespread implications for the cascade of
      developmental events during embryogenesis, formation, and vascularization of the
      placenta. Large-scale zygosity testing at birth could be the template for
      analysis of twin outcomes and their biologic causes.

PMID- 8741867
TI  - Correlations of placental vascular anatomy and clinical outcomes in 69
      monochorionic twin pregnancies.
AB  - Monochorionic monozygotic twins frequently suffer complications from the presence
      of vascular anastomoses in their monochorionic placentas. Also, sharing of
      perfusion zones may be unequal, leading to marked growth discordance. This paper
      analyzes four measures of perinatal outcome (gestational age at delivery,
      perinatal mortality, birth weight discordance, and presence/absence of
      hydramnios) according to the vascular patterns of the monochorionic placentas.
      The worst clinical outcomes were associated with arteriovenous anastomoses in the
      absence of arterio-arterial and veno-venous anastomoses. The vascular patterns of
      monochorionic placentas cause significant fetal environmental differences within
      pairs of monochorionic monozygotic twins. These differences may cause life-long
      discordance for several phenotypic traits that are not genetically based, and
      which cause monochorionic monozygotic twins to be "non-identical."

PMID- 8741868
TI  - Genetic contribution to DZ twinning.
AB  - The genetic contribution to dizygotic (DZ) twinning was investigated using 6,596
      twin pairs from the Australian Twin Registry who provided information on other
      twins in their families. Responses were classified by the zygosity (DZ;
      monozygotic [MZ]) of the proband twins and by the relationship and zygosity of
      related twins. MZ probands and MZ twins reported by DZ probands were used as
      controls and assumed to be independent of any genetic influence. Significantly
      higher proportions of DZ twins were found in the families of DZ probands compared
      to the families of MZ probands for the following relationships: sibs of probands,
      proband mothers, offspring of sisters of proband mothers, and offspring of female
      probands (P < 0.001 in each case). The latter 2 relationships were used to
      estimate risk ratios of 1.7 for sisters of mothers of DZ twins, and 2.5 for
      offspring of female DZ twins. No greater tendency to DZ twinning in close
      relatives was found in mothers who bore DZ twins at a younger age than at an
      older age.

PMID- 8741869
TI  - Zygosity and placental anatomy in 15 consecutive sets of spontaneously conceived
      triplets.
AB  - Most triplets are trizygotic because they result from assisted reproduction.
      Prognosis is generally good. We analyzed 15 sets of triplets who were conceived
      spontaneously. Six sets were monozygotic, 7 were dizygotic, and only 2 sets were
      trizygotic. Considered as 45 twin pairs, 25 pairs (56%) were monozygotic. Twenty
      percent of these twins died as a result of twin-twin transfusion. Spontaneously
      conceived triplets have high risks compared with those resulting from assisted
      reproduction. These risks result from a high proportion of monozygotic embryos,
      many of whom have monochorionic placentas with vascular anastomoses, causing twin
      to-twin transfusion.

PMID- 8741870
TI  - Two pairs of male monozygotic twins discordant for Wiedemann-Beckwith syndrome.
AB  - Wiedemann-Beckwith syndrome (WBS) is a congenital anomaly syndrome which
      classically consists of exomphalos, macroglossia, and gigantism. The syndrome is
      also associated with a variety of minor anomalies and affected individuals have
      an increased risk of developing rare embryonal cell tumors. To date, 15
      monozygotic (MZ) twin pairs have been reported of which 13 are discordant for
      WBS. All except one pair of the discordant WBS twin pairs have been female. We
      report two pairs of male MZ twins, each discordant for WBS.

PMID- 8741871
TI  - Genetic modelling of dizygotic twinning in pedigrees of spontaneous dizygotic
      twins.
AB  - The inheritance of spontaneous dizygotic (DZ) twinning was investigated in 1,422
      three-generation pedigrees ascertained through mothers of spontaneous DZ proband
      twins. DZ twinning was modelled as a trait expressed only in women. The
      penetrance was modelled first as a parity independent and secondly as parity
      dependent. The observed frequencies of maternal and paternal grandmothers with DZ
      twins differed significantly from the expectations under an X-linked mode of
      inheritance. Complex segregation analysis showed that the parity-independent
      phenotype of "having DZ twins" was consistent with an autosomal monogenic
      dominant model, with a gene frequency of 0.035 and a female-specific lifetime
      penetrance of 0.10. Recessive, polygenic, and sporadic models were rejected. The
      autosomal dominant model revealed a strong robustness against a changing
      population prevalence and the loss of information due to the presence of same
      sexed twin pairs of unknown zygosity. When DZ twinning was modelled as a parity
      dependent trait, the data were compatible with an autosomal dominant model with a
      gene frequency of 0.306 and a penetrance of 0.03 per birth for female gene
      carriers.

PMID- 8741872
TI  - Blood group chimerism in human multiple births is not rare.
AB  - Twin blood group chimerism seems to be very rare in humans. The 30-40 previously
      reported cases usually were found by mere coincidence during routine blood
      grouping in hospitals or blood banks. Usually in these cases frank blood group
      mixtures of, for example, 50/50%, 25/75%, or 5/95% at most were seen. Smaller
      percentages are very difficult to notice during routine work-up. Using a
      sensitive fluorescence technique (sensitivity > 0.01%) we detected blood group
      chimerism in 32/415 (8%) twin pairs and 12/57 (21%) triplet pairs, respectively,
      which is a higher incidence than reported previously.

PMID- 8741873
TI  - Trisomy 15 mosaicism and uniparental disomy (UPD) in a liveborn infant.
AB  - We describe a liveborn infant with uniparental disomy (UPD) with trisomy 15
      mosaicism. Third trimester amniocentesis yielded a 46,XX/47,XX,+15 karyotype.
      Symmetrical growth retardation, distinct craniofacies, congenital heart disease,
      severe hypotonia and minor skeletal anomalies were noted. The infant died at 6
      weeks of life. Peripheral lymphocyte chromosomes were "normal" 46,XX in 100
      cells. Parental lymphocyte chromosomes were normal. Skin biopsy showed 47,XX,+15
      in 80% of fibroblasts and results were equivalent in fibroblasts from autopsy
      lung tissue. Molecular analysis revealed maternal uniparental heterodisomy for
      chromosome 15 in the 46,XX cell line. We describe an emerging phenotype of
      trisomy 15 mosaicism, confirm that more than one tissue should be studied in all
      cases of suspected mosaicism, and suggest that UPD be considered in all such
      cases.

PMID- 8741874
TI  - Clouston syndrome: an ectodermal dysplasia without significant dental findings.
AB  - The ectodermal dysplasias are a heterogeneous group of conditions primarily
      affecting the hair, teeth, nails, and skin, and are classified according to the
      tissue(s) affected. The classification categories are: (1) abnormalities of hair,
      (2) dental defects, (3) abnormalities of nail morphology, and (4) dyshidrosis.
      Individuals are grouped according to defects present with findings from two or
      more categories required for diagnosis. As this classification method is based on
      phenotype, variable expression or small family size may well have an impact on
      diagnosis. We report a four-generation family with a hair-nail (1-3) dysplasia
      with nail morphology that is typical of Clouston syndrome. All affected relatives
      have thick, discolored, hyperconvex nails with onycholysis, varying degrees of
      hair involvement, and are hidrotic. They lack hyperkeratosis and multiple caries
      as originally described in Clouston syndrome. We propose that morphologic
      abnormalities of the teeth may not occur in the phenotype of Clouston syndrome
      and that it can be considered a hair-nail (1-3) dysplasia.

PMID- 8741875
TI  - Dopamine D4 receptor variant in Africans, D4valine194glycine, is insensitive to
      dopamine and clozapine: report of a homozygous individual.
AB  - The D4Valine194Glycine receptor is a variant of the dopamine D4 receptor and is
      found in 12.5% of the Afro-Caribbean population. Glycine replaces valine at a
      position one amino acid away from a serine which is critical for the attachment
      of dopamine. To determine whether this mutation had an effect on the properties
      of the dopamine D4 receptor, we constructed this variant and tested the
      sensitivity of the expressed protein with various drugs. We found that the
      variant receptor was two orders of magnitude less sensitive to dopamine,
      clozapine and olanzapine. The variant receptor was insensitive to guanine
      nucleotide, indicating the absence of a high-affinity state or functional state.
      The one 15-year-old individual found homozygous for this variant also had sickle
      cell disease. The patient revealed an overall pattern of low weight and no
      axillary or pubic hair.

PMID- 8741876
TI  - Mitochondrial DNA sequence analysis of four Alzheimer's and Parkinson's disease
      patients.
AB  - The mitochondrial DNA (mtDNA) sequence was determined on 3 patients with
      Alzheimer's disease (AD) exhibiting AD plus Parkinson's disease (PD)
      neuropathologic changes and one patient with PD. Patient mtDNA sequences were
      compared to the standard Cambridge sequence to identify base changes. In the
      first AD+PD patient, 2 of the 15 nucleotide substitutions may contribute to the
      neuropathology, a nucleotide pair (np) 4336 transition in the tRNA(Gln) gene
      found 7.4 times more frequently in patients than in controls, and a unique np 721
      transition in the 12S rRNA gene which was not found in 70 other patients or 905
      controls. In the second AD+PD patient, 27 nucleotide substitutions were detected,
      including an np 3397 transition in the ND1 gene which converts a conserved
      methionine to a valine. In the third AD+PD patient, 2 polymorphic base
      substitutions frequently found at increased frequency in Leber's hereditary optic
      neuropathy patients were observed, an np 4216 transition in ND1 and an np 13708
      transition in the ND5 gene. For the PD patient, 2 novel variants were observed
      among 25 base substitutions, an np 1709 substitution in the 16S rRNA gene and an
      np 15851 missense mutation in the cytb gene. Further studies will be required to
      demonstrate a causal role for these base substitutions in neurodegenerative
      disease.

PMID- 8741877
TI  - Exclusion of primary congenital glaucoma (buphthalmos) from two candidate regions
      of chromosome arm 6p and chromosome 11.

PMID- 8741878
TI  - Midline field defects and Hirschsprung disease.

PMID- 8741879
TI  - Bleeding Meckel's diverticulum presenting as focal extravasation on pertechnetate
      scintigraphy.
AB  - The evaluation of gastrointestinal hemorrhage may include a Meckel's scan,
      particularly in children. Typically, a Meckel's diverticulum shows discrete,
      focal uptake in the right lower abdomen. The authors describe an adult whose
      bleeding Meckel's diverticulum manifested as brisk, intermittent intraluminal
      tracer extravasation.

PMID- 8741880
TI  - Transient false-positive hepatobiliary scan associated with ceftriaxone therapy.
AB  - Drug related false-positive hepatobiliary imaging is uncommon. The authors
      present a case of a 54-year-old woman who was treated with intravenous
      ceftriaxone for bacterial meningitis. Symptoms of acute cholecystitis
      subsequently developed and a sonogram revealed a gallstone. A Tc-99m DISIDA
      hepatobiliary study was positive for cystic duct obstruction. After
      discontinuation of ceftriaxone, the patient's clinical condition improved and, 2
      weeks later, a repeat hepatobiliary scan was normal. High doses of ceftriaxone
      and prolonged administration may lead to formation of pseudocholelithiasis and
      signs of acute cholecystitis. Although this condition is usually benign and
      reversible, discontinuation of the drug is warranted when symptoms of acute
      cholecystitis are accompanied by a positive hepatobiliary scan.

PMID- 8741881
TI  - Hepatocellular adenoma case report with Tc-99m SC uptake and radiologic
      correlation.
AB  - An uncommon case of hepatocellular adenoma is presented. In this case, the tumor
      was Tc-99m SC avid rather than the typical pattern of no uptake. Liver
      scintigraphy was able to demonstrate that the tumor originated from the liver
      correlating with ultrasound and computed tomography. Background information on
      hepatocellular adenomas, a differential diagnosis, and a logical approach to
      similar liver lesions is discussed.

PMID- 8741882
TI  - MAG3 renal transplant tomography SPECT with a non-SPECT agent.
AB  - The authors encountered a renal transplant patient in whom tubular stasis
      permitted sufficient time to perform SPECT using Tc-99m MAG3. SPECT revealed a
      defect that was not apparent on the planar study. Renal biopsy showed acute
      vascular rejection. On a subsequent Tc-99m MAG3 SPECT study the defect had
      resolved.

PMID- 8741883
TI  - The use of low-dose intravenous insulin in clinical myocardial F-18 FDG PET
      scanning.
AB  - The effectiveness of low-dose intravenous insulin boluses to improve study
      quality in F-18 FDG myocardial scans is investigated. Seventeen patients were
      imaged using a protocol in which only diabetic patients with fasting blood
      glucose levels > 8 mmol/l were given insulin. Fifty-three patients were imaged
      using a protocol in which all patients were given 1-3 IU intravenously of insulin
      immediately before F-18 FDG injection, based on fasting blood glucose levels.
      Scan quality was rated as poor, good, or excellent. Using the conventional
      protocol, 29% of the scans were poor quality (uniterpretable), 47% were good, and
      23% were excellent. Using the low-dose intravenous insulin boluses protocol; 2%
      were poor, 53% were good, and 45% were excellent (P = 0.01). There were no
      significant differences in the proportion of diabetic patients, age, or fasting
      blood glucose levels. Low-dose intravenous insulin bolus is an easy and safe
      method of improving myocardial F-18 FDG scan quality in nondiabetic and diabetic
      patients.

PMID- 8741884
TI  - Diagnostic value of Tc-99m sestamibi gated SPECT to assess viability in a patient
      after acute myocardial infarction.
AB  - The case of a 56-year-old woman who was admitted with an acute anteroseptal
      myocardial infarction showed severely decreased left ventricular function and
      regional wall motion abnormalities on planar Tc-99m gated blood pool imaging. Tc
      99m sestamibi stress SPECT imaging demonstrated residual peri-infarct ischemia.
      At angiography, a solitary severe proximal left anterior descending stenosis was
      successfully dilated. Later, because of recurrent chest pain, a second Tc-99m
      sestamibi stress-rest SPECT was performed to exclude restenosis. Because the
      question of viability within the infarct region had also been asked, a gated
      protocol was applied and compared to TI-201 rest-redistribution SPECT. Both tests
      pointed to the existence of tissue viability in the septal region, without
      evidence for stress ischemia. The patient was then medically treated. One year
      later, because of angina, Tc-99m gated SPECT blood pool imaging showed a
      spectacular increase in left ventricular function and a dramatic improvement in
      regional wall motion. Angiographic data confirmed these findings and there was no
      significant restenosis. Thus, Tc-99m sestamibi gated SPECT may be helpful in
      predicting viability and recovery of function in patients with severely impaired
      left ventricular regional wall motion after acute myocardial infarction.

PMID- 8741885
TI  - Prostatic calcifications detected on Tc-99m MDP bone scan mimicking bone
      metastasis.
AB  - Uptake of Tc-99m MDP tracer was noted within prostatic calcifications in a 48
      year-old man with no known malignancy who underwent a three-phase bone scan for
      left knee and thigh pain. Routine anterior and posterior views of the pelvis
      demonstrated focal tracer uptake within the right pubic bone, which mimicked a
      metastatic lesion. Additional imaging showed the uptake to be extraosseous and
      localized within the prostate in a distribution similar to the extensive
      prostatic calcifications seen on the corresponding plain film and computed
      tomography examinations of the pelvis. This unusual presentation illustrates
      another potential artifact that may be present in scintigraphic bone imaging of
      the pelvis.

PMID- 8741886
TI  - Ectopic parathyroid adenomas: multi-imaging modalities and its management.
AB  - Advancements in imaging technology have led to better diagnoses of ectopic
      parathyroid adenomas. Although surgery is curative in the majority of patients
      with parathyroid adenomas in normal preoperative locations, imaging is definitely
      required in ectopic adenomas in the neck and more importantly in the chest. The
      various imaging modalities used in the diagnosis of parathyroid adenomas are
      isotopic techniques, MRI, CT, ultrasound, arteriography, and venous sampling for
      parathormone. This review presents four patients studied with different
      diagnostic techniques resulting in cures with surgery or arteriographic ablation.
      The literature survey suggests the sensitivity of Tc-99m MIBI scanning to be more
      than 90%, MRI 70-75%, and CT scanning slightly lower. On the basis of the
      authors' experience and a literature review, a combination of MIBI scanning and
      MRI appears to be the most logical approach. If these two tests do not provide
      sufficient diagnostic confidence, then CT or a contrast arteriogram should be
      considered. Recent advances in arteriography/catheters have made angiographic
      ablation with alcohol or contrast material possible in patients who cannot
      undergo surgery.

PMID- 8741887
TI  - Three-phase skeletal scintigraphy in gouty arthritis: an example of potential
      diagnostic pitfalls in radiopharmaceutical imaging of the extremities for
      infection.
AB  - The three-phase bone scan has been shown to be useful in the diagnosis of
      osteomyelitis, with a high sensitivity and specificity under optimal conditions.
      However, there are many causes of focally-increased uptake of Tc-99m
      diphosphonates in the extremities that may mimic infection, especially when there
      is increase on all three phases. Radiolabeled leukocyte scintigraphy is often
      performed in this clinical setting, although many pitfalls resulting in false
      positive scans still remain. The authors present three cases of gouty arthritis
      in which skeletal scintigraphy illustrates this lack of specificity. Further
      causes of increased extremity uptake are reviewed, with attention to those that
      have been reported to show an increase on all three phases of the bone scan.
      Additional factors that can improve the specificity of the bone scan are
      discussed, as are the panoply of more recent scintigraphic approaches aimed at
      distinguishing infection from aseptic inflammation in the extremity.
      Unfortunately, no nuclear medicine procedure to date has proven itself to be
      reliably specific for infection.

PMID- 8741888
TI  - Generalized bone marrow metastases. High liver uptake on bone marrow
      immunoscintigraphy associated with extramedullary hematopoiesis.
AB  - Increased hepatic uptake and absent bone marrow uptake on bone marrow
      immunoscintigraphy has been reported after the formation of human antimurine
      antibodies. A case of generalized bone marrow metastases is presented, in whom an
      elevated liver uptake on bone marrow immunoscintigraphy proved to be associated
      with extramedullary hematopoiesis. Extramedullary hematopoiesis should be
      included as a possible cause of a disproportionately elevated liver uptake on
      bone marrow immunoscintigraphy, especially on initial studies, or on repeat
      studies with low human antimurine antibody titers. Tc-99m labeled BW 250/183
      immunoscintigraphy may aid in the localization of suspected sites of
      extramedullary hematopoiesis.

PMID- 8741889
TI  - The scintigraphic features of giant-cell tumors in relation to other imaging
      modalities.
AB  - Thirty-three patients with untreated giant-cell tumors of bone were studied with
      Tc-99m phosphate scintigraphy. The scintigraphic patterns of the tumors were
      varied and the tumors exhibited extended uptake of radioactivity in the majority
      of cases. The homogeneously diffuse pattern and the nonhomogeneous "doughnut" and
      "blob" patterns are described. The scintigraphic patterns of giant-cell tumors
      are considered in the light of the radiographic, angiographic, CT, and MR imaging
      studies and the histopathologic findings.

PMID- 8741890
TI  - Accumulation of Ga-67 citrate in a tuberculous splenic abscess. Report of a rare
      case.
AB  - A case of 65-year-old man with tuberculous splenic abscess is presented. The Ga
      67 citrate scan revealed three focal areas of increased uptake in the left upper
      quadrant of the abdomen. The combined Tc-99m SC/Ga-67 scans revealed that these
      Ga-67 avid lesions localized in the splenic photon-deficit areas found in the Tc
      99m SC scan. This case demonstrated the usefulness of Ga-67 imaging in a survey
      of fever of unknown origin in unsuspected tuberculous splenic abscess.

PMID- 8741891
TI  - Intense uptake of In-111 satumomab pendetide in an inflammatory mass.
AB  - Intensely increased upper abdominal uptake of In-111 labeled anti-tumor
      associated glycoprotein in a patient with a history of pancreatic carcinoma
      persisted over 6 days in the same location. At laparotomy chronic inflammation,
      fibrosis, calcification, and lymph node granulomas were found, but no tumor. The
      patient remained tumor free 8 months later.

PMID- 8741892
TI  - Hepatic hydrothorax. Diagnosis and management.
AB  - Twelve cases of right hepatic hydrothorax are reported. Tc-99m SC that was
      injected intraperitoneally and intrapleurally provided evidence of a one-way flow
      of fluid from the peritoneal to the pleural cavity. Eight patients, whose
      hydrothorax was refractory to sodium restriction, diuretics and repeated
      thoracenteses, were treated by endopleural tetracycline instillation. The
      pathogenetic role of the diaphragmatic defect and the diagnostic usefulness of
      radionuclide imaging are stressed.

PMID- 8741893
TI  - Splenosis in a patient with autoimmune thrombocytopenia.

PMID- 8741894
TI  - Demonstration of metastatic melanoma by Tc-99m sestamibi imaging.

PMID- 8741895
TI  - Suppressed hepatic uptake of Ga-67 after chemotherapy for non-Hodgkin's lymphoma.

PMID- 8741896
TI  - Detection of cutaneous metastatic melanoma with TI-201 scintigraphy.

PMID- 8741897
TI  - Ga-67 imaging of tumoral calcinosis associated with secondary
      hyperparathyroidism.

PMID- 8741898
TI  - Increased uptake of I-123 IMP in peritoneal metastases of hepatocellular
      carcinoma.

PMID- 8741899
TI  - The detection of cerebrospinal fluid block with Tc-99m DTPA cerebral
      ventriculography.

PMID- 8741900
TI  - TI-201 uptake in thymic carcinoma.

PMID- 8741902
TI  - Scintigraphic findings of epidermoid carcinoma mimicking findings of malignant
      otitis externa.

PMID- 8741901
TI  - Ectopic parathyroid imaging with Tc-99m sestamibi.

PMID- 8741903
TI  - Renal artery stenosis secondary to Takayasu's arteritis demonstrated on Tc-99m
      MAG3 renal scan correlation with conventional angiography.

PMID- 8741906
TI  - False-positive morphine augmented hepatobiliary imaging.

PMID- 8741908
TI  - Unique demographic situation in the United Arab Emirates.

PMID- 8741905
TI  - Ga-67 and In-111 pentreotide imaging.

PMID- 8741904
TI  - Diffuse pulmonary uptake of Tc-99m MDP in sarcoidosis.

PMID- 8741907
TI  - Current readings in nuclear medicine.

PMID- 8741909
TI  - Who is a carrier? Detection of unsuspected mutations in 21-hydroxylase
      deficiency.
AB  - Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a common
      autosomal-recessive disorder. During our routine genotyping of affected
      individuals and their relatives using allele-specific oligonucleotide
      hybridization and single-strand conformational polymorphism analysis, we
      identified two families each segregating three mutations. In both families, a
      mutation known to be associated with 21-hydroxylase deficiency was identified in
      healthy individuals but was not detected in the propositus. The propositus in
      family 1 was shown to be a homozygous carrier for G at nucleotide 655, which
      alters the splice acceptor site at exon 3. The propositus in family 2 carried the
      same splicing mutation on the maternal allele and a gene deletion/conversion on
      the paternal allele. In both families, other clinically unaffected relatives
      carried the Q318X mutation in exon 8. If molecular diagnostic studies had been
      limited to the mutation carried by the propositi, relatives would have been
      misinformed regarding their status as carriers or mildly affected individuals.
      The findings in these two families emphasize the high frequency of alleles
      causing 21-hydroxylase deficiency in the population.

PMID- 8741910
TI  - Segregation of a paternal insertional translocation results in partial 4q
      monosomy or 4q trisomy in two siblings.
AB  - A genetics evaluation was requested for a 6-week-old infant with multiple
      congenital malformations including mild craniofacial anomalies, truncal
      hypotonia, hypospadias, and a ventriculoseptal defect. Blood obtained for
      chromosome analysis revealed an abnormal chromosome 4. Paternal chromosome
      analysis showed a 46,XY, inv ins (3;4)(p21.32;q25q21.2), inv(4)(p15.3q21.2)
      karyotype. Therefore, the proband's chromosome 4 was the unbalanced product of
      this insertional translocation from the father resulting in partial monosomy 4q.
      Additionally, the derivative 4 had a pericentric inversion which was also seen in
      the father's chromosome 4. During genetic counseling, the proband's 2-year-old
      brother was evaluated. He was not felt to be abnormal in appearance, but was
      described as having impulsive behavior. Chromosome analysis on this child
      revealed 46,XY,der(3)inv ins(3;4)(p21.32;q25q21.2)pat. This karyotype results in
      partial trisomy 4q. FISH using two-color "painting" probes for chromosomes 3 and
      4 confirmed the G-banded interpretation in this family. The segregation seen in
      this family resulted in both reciprocal products being observed in the two
      children, with partial 4q monosomy showing multiple congenital anomalies, and
      partial 4q trisomy showing very few phenotypic abnormalities.

PMID- 8741911
TI  - Identification and molecular confirmation of a small chromosome 10q duplication
      [dir dup(10)(q24.2-->q24.3)] inherited from a mother mosaic for the abnormality.
AB  - We describe a family in which two siblings exhibited developmental delay, reduced
      muscle tone and mild muscle weakness. Cytogenetic evaluation demonstrated that
      both children had a tandem duplication of a small portion of the long arm of
      chromosome 10 [46,XX or XY,dir dup(10)(q24.2-->q24.3)], inherited from their
      clinically normal mother, who was found to be mosaic for the duplicated
      chromosome 10. Fluorescence in situ hybridization approaches, including total
      chromosome painting and the use of regional specific cosmid probes, were used to
      confirm the chromosome 10q origin of the duplicated material. This is the
      smallest confirmed duplication of this portion of chromosome 10 reported to date.

PMID- 8741912
TI  - Duplication of 7p: further delineation of the phenotype and restriction of the
      critical region to the distal part of the short arm.
AB  - We report on a patient with duplication of 7p15-->pter and review the literature.
      Patients with partial duplication of the distal 7p, including only the distal
      segment 7p15-->pter, have a syndrome comparable to that of patients with a larger
      or complete duplication of 7p. This suggests that the critical region for the
      dup(7p) phenotype is restricted to 7p15-->pter. The complete clinical phenotype
      of dup(7)(p15-->pter) includes mental retardation, skull anomalies, large
      anterior fontanel, cardiovascular defects, joint dislocation and contraction, and
      gastrointestinal and genital defects. Recognition of the clinical spectrum in
      patients with a smaller duplication of 7p, and the assignment of this critical
      region, should prove valuable for accurate counseling, prediction of outcome, and
      further gene mapping.

PMID- 8741913
TI  - Longitudinal study of the cognitive development in children with Williams-Beuren
      syndrome.
AB  - Crisco [1990: Clin Res 38:536A] reported stability of IQs in a group of 14
      children with Williams-Beuren syndrome (WBS) over a 5-year period and concluded
      that they display a development rate similar to normal children. The aim of our
      study was to examine the stability of the development of nonverbal reasoning
      abilities over a period of 2 years using two methods. We studied 18 children with
      WBS (9 girls, 9 boys) with a mean age of 6.6 years (range: 4.4-10.6 yr) at year
      one (T1), and approximately two years later (T2) at the average age of 8.6 years
      (range: 5.11-12.7 yr). The Columbia Mental Maturity Scale (CMM) and the Draw A
      Person Test were administered. The results show that the IQs resulting from the
      Draw A Person Test were stable over the 2-year period (T1: mean IQ = 63.5, T2:
      mean IQ = 65, t = 0.63), and display a significant correlation between the two
      methods (r = 0.547, P = 0.01). Furthermore, the correlation between the two tests
      (CMM and Draw A Person Test) at the second assessment is high and significant (r
      = 0.56, P = 0.01). The mean IQs at T2 can be classified as mild mental
      retardation. A notable result is the significant decrease of the IQs according to
      the CMM (T1: mean IQ = 77, T2: mean IQ = 68, t = 2.69, P = 0.01). These results
      suggest that the developmental outcome of children with WBS varies in specific
      areas of cognitive function over a 2-year period.

PMID- 8741914
TI  - Does periconceptional multivitamin use reduce the risk of neural tube defects
      associated with other birth defects? data from two population-based case-control
      studies.
AB  - The role of periconceptional folic acid in the prevention of neural tube defects
      (NTDs) is well established. However, it is not clear whether a protective effect
      exists for the subset of nonsyndromic NTD with other "unrelated" major structural
      birth defects (NTD-multiples). This question is important to investigate because
      of shared pathogenetic mechanisms between NTD and other types of birth defects,
      and because of the epidemiologic differences that have been shown between NTD
      multiples and NTD-singles. We analyzed data from two population-based case
      control studies of NTDs, Atlanta 1968-1980, and California 1989-1991, to assess
      whether periconceptional multivitamin use reduces the risk of NTD-multiples.
      Maternal vitamin histories were assessed for 47 and 65 NTD-multiples cases and
      3,029 and 539 control babies in Atlanta, and California, respectively. There was
      a substantial risk reduction associated with periconceptional multivitamin use (
      3 to +3 months) for NTD-multiples (pooled odds ratio = 0.36, 95% C.I. 0.18-0.72)
      that persisted after adjustment for maternal race/ethnicity and education. Also,
      no specific types of NTDs or NTDs with specific defects explained the risk
      reduction with vitamin use. These data suggest that multivitamins reduce the risk
      of nonsyndromic NTD cases associated with other major birth defects. The
      implication of this finding for the role of vitamins in the prevention of non-NTD
      birth defects should be further explored.

PMID- 8741915
TI  - HLA DRB1*DQB1* haplotype in HTLV-I-associated familial infective dermatitis may
      predict development of HTLV-I-associated myelopathy/tropical spastic paraparesis.
AB  - A possible causal association between infective dermatitis and HTLV-I infection
      was reported in 1990 and confirmed in 1992. We now report familial infective
      dermatitis (ID) occurring in a 26-year-old mother and her 9-year-old son. The
      mother was first diagnosed with ID in 1969 at the age of 2 years in the
      Dermatology Unit at the University Hospital of the West Indies (U.H.W.I.) in
      Jamaica. The elder of her 2 sons was diagnosed with ID at the age of 3 years,
      also at U.H.W.I. Both mother and son are HTLV-I-seropositive. A second, younger
      son, currently age 2 years, is also HTLV-I-seropositive, but without clinical
      evidence of ID. Major histocompatibility complex (MHC), class II, human leucocyte
      antigen (HLA) genotyping documented a shared class II haplotype, DRB1*DQB1* (1101
      0301), in the mother and her 2 sons. This same haplotype has been described among
      Japanese patients with HTLV-I-associated myelopathy/tropical spastic paraparesis
      (HAM/TSP), and has been associated with a possible pathologically heightened
      immune response to HTLV-I infection. The presence of this haplotype in these
      familial ID cases with clinical signs of HAM/TSP may have contributed to their
      risk for development of HAM/TSP. The unaffected, HTLV-I-seropositive younger son
      requires close clinical follow-up.

PMID- 8741916
TI  - Aplasia cutis congenita, high myopia, and cone-rod dysfunction in two sibs: a new
      autosomal recessive disorder.
AB  - We report on a brother and a sister with congenital nystagmus, cone-rod
      dysfunction, high myopia, and aplasia cutis congenita on the midline of the scalp
      vertex. To our knowledge this familial oculocutaneous condition, transmitted as
      an autosomal recessive trait, has not been reported previously.

PMID- 8741917
TI  - Terminal deletion of the long arm of chromosome 3 [46,XX,del(3)(q27-->qter)].
AB  - We report on a terminal deletion of the long arm of chromosome 3
      [46,XX,del(3)(q27-->qter)] in a female newborn infant who died 45 hours after
      delivery and had multiple congenital abnormalities including bilateral
      anophthalmia, congenital heart disease, and abnormal genitalia. The findings are
      compared to those of four previously reported cases with terminal del (3q).

PMID- 8741918
TI  - Epidemiology of osteochondrodysplasias: changing trends due to advances in
      prenatal diagnosis.
AB  - The osteochondrodysplasias (skeletal dysplasias) are a heterogeneous group of
      disorders characterized by abnormalities in cartilage and bone growth and
      development. Some of these disorders are detectable during the second trimester
      by sonographic techniques. We ascertained cases of osteochondrodysplasias in
      elective pregnancy terminations, stillborn infants older than 20 gestational
      weeks, and liveborn infants diagnosed by the fifth day of life as part of an
      ongoing active malformation surveillance program. Forty-nine cases of
      osteochondrodysplasias were identified among approximately 126,000 deliveries at
      Brigham and Women's Hospital (BWH) during a 15-year period (Feb. 16, 1972-Feb.
      15, 1975; Jan. 1, 1979-Dec. 31, 1990). When cases delivered to women who had
      planned to deliver at another hospital but were transferred for high-risk care
      (transfers) were excluded, the prevalence rate was 2.14 cases per 10,000
      deliveries. During the early period (1972-1975) no cases were suspected
      prenatally, while during the 1988-1990 period, 80% of all cases and 57% of cases
      delivered to women who had always planned to deliver at BWH (non-transfers) were
      suspected by ultrasonography. Birth status changed through our period of
      surveillance. In the final 3-year period (1988-1990), 40% of all cases and 29% of
      non-transfers with osteochondrodysplasias were pregnancy terminations, compared
      to none during the 1972-1975 period. The increasing frequency of pregnancy
      terminations complicated the diagnosis of these conditions. Despite extensive
      evaluation, a definitive diagnosis was not possible in 8 of 49 cases (16%).
      Biochemical and molecular genetic methods of diagnosis will continue to become
      more important if the current trend of wide utilization of prenatal sonography
      and termination of affected pregnancies continues.

PMID- 8741919
TI  - Occipital encephalocele and MURCS association: case report and review of central
      nervous system anomalies in MURCS patients.
AB  - The combination of MURCS association (Mullerian duct and renal agenesis, upper
      limb and rib anomalies) and occipital encephalocele occurred in a stillborn girl
      of 41 weeks gestation. The malformations are compatible with a defect in the
      organization of the paraxial mesoderm that gives rise to occipital, cervical, and
      thoracic somites and adjoining intermediate mesoderm. These structures contribute
      to the occipital bone, cervical spine, upper limbs, and urogenital system. Brain
      imaging may be useful in assessing MURCS patients, if cranial malformations prove
      to be clinically important in these individuals.

PMID- 8741920
TI  - Is there a Baller-Gerold syndrome?

PMID- 8741921
TI  - Fanconi anemia in brothers initially diagnosed with VACTERL association with
      hydrocephalus, and subsequently with Baller-Gerold syndrome.
AB  - Two brothers with presumed Baller-Gerold syndrome, one of whom was previously
      diagnosed with the association of vertebral, cardiac, renal, limb anomalies, anal
      atresia, tracheo-esophageal fistula (VACTERL) association with hydrocephalus,
      were evaluated for chromosome breakage because of severe thrombo cytopenia in one
      of them. Spontaneous and clastogen-induced breakage was markedly increased in
      both patients as compared to control individuals. Clinical manifestations and
      chromosome breakage, consistent with Fanconi anemia, in patients with a prior
      diagnosis of either Baller-Gerold syndrome, reported earlier in one other patient
      [Farrell et al., 1994: Am J Med Genet 50:98-99], or with VACTERL association with
      hydrocephalus, recently reported in 3 patients [Toriello et al., 1991: Proc
      Greenwood Genet Center 11:142; Porteus et al., 1992: Am J Med Genet 43:1032
      1034], underline the clinical heterogeneity of Fanconi anemia and raise the
      question of whether these syndromes are distinct disorders or phenotypic
      variations of the same disease.

PMID- 8741922
TI  - Fryns syndrome phenotype and trisomy 22.
AB  - Trisomy 22 was detected in a 32-week-old fetus born to an overweight mother with
      hypertension. Severe intrauterine growth retardation was associated with
      phenotypic manifestations of Fryns syndrome: diaphragmatic hernia, facial
      defects, and nail hypoplasia with short distal fifth phalanges. This is the
      second report of congenital diaphragmatic hernia in trisomy 22. This case
      demonstrates the importance of karyotyping malformed fetuses or newborns, even if
      a nonchromosome syndrome seems identifiable on clinical grounds. To date, at
      least 10 cases of Fryns syndrome have been reported without chromosome analysis.

PMID- 8741923
TI  - Treacher Collins syndrome: phenotypic variability in a family including an infant
      with arhinia and uveal colobomas.
AB  - We report extreme expression of Treacher Collins syndrome in an infant with
      arhinia, anotia, absent zygomatic bones, hypoplastic mandibular rami, and
      bilateral coloboma of iris, choroid plexus, and optic nerves. The Treacher
      Collins phenotype was mildly expressed in the mother and moderately in the
      sister. The father had no signs and was not ruled out as the father by DNA
      fingerprinting, thus making homozygosity by descent in the severely affected son
      very unlikely.

PMID- 8741924
TI  - Frontonasal malformation and cloacal exstrophy: a previously unreported
      association.
AB  - We report on a child with frontonasal malformation (FNM) and cloacal exstrophy, a
      combination of findings that have not been reported previously. In FNM and
      cloacal exstrophy, associated malformations are rare. FNM and cloacal exstrophy
      both represent abnormalities of the development of the midline field; this
      combination of anomalies in this patient suggests an impairment of caudal and
      cranial midline development during blastogenesis.

PMID- 8741925
TI  - Association of prune belly with cleft lip.

PMID- 8741926
TI  - Cognitive and psychosocial functioning of patients with congenital nephrogenic
      diabetes insipidus.
AB  - Mental retardation (MR) is generally considered one of the main complications of
      congenital nephrogenic diabetes insipidus (NDI). However, psychometric studies of
      NDI patients are scarce and outdated. In the present study, 17 male NDI patients
      underwent psychological evaluation. Total intelligence quotient of 14 patients
      was within (n = 13) or above (n = 1) the normal range, 1 patient had an
      intelligence score between -1 and -2 standard deviations (S.D.) and 2 young
      patients had a general cognitive index more than 2 S.D. below the norm. Attention
      deficit hyperactivity disorder criteria were met by 8 out of 17 patients and
      scores on short-term memory were low in 7 out of 10. No relation between test
      performances and age at diagnosis or hypernatremia could be found, with the
      exception of a negative correlation between age at start of therapy and verbal IQ
      in one age group. Although several explanations for an association between MR and
      NDI can be postulated, it seems that the current prevalence of MR among patients
      with this disease is considerably lower than suggested in literature.

PMID- 8741927
TI  - Atrioventricular septal defect with pulmonary atresia in DiGeorge anomaly:
      expansion of the cardiac phenotype.

PMID- 8741928
TI  - Inheritance in Kabuki make-up (Niikawa-Kuroki) syndrome.

PMID- 8741929
TI  - Another case of the human homologue of the mouse mutant disorganization.

PMID- 8741930
TI  - EEOC compliance manual for the ADA and genetic discrimination.

PMID- 8741932
TI  - Lambdoid synostosis is an overdiagnosed condition.

PMID- 8741931
TI  - Autosomal dominant Russell-Silver syndrome.

PMID- 8741933
TI  - Orally delivered methadone as a reinforcer in rhesus monkeys.
AB  - Methadone usually is taken orally for drug abuse treatment in humans but oral
      methadone self-administration by laboratory animals has not been investigated
      extensively. The present study examines acquisition and maintenance of oral
      methadone maintained responding in four adult male rhesus monkeys. Drug solution
      was available from one liquid delivery system and water from a second system
      during daily 3-h sessions. Locations of liquids were reversed each session, and
      liquid (0.65 ml per delivery) was delivered according to a fixed-ratio
      reinforcement schedule. Initially a test for the reinforcing effects of 0.00625
      0.4 mg/ml methadone solutions was carried out but a consistent preference for
      drug over water was not seen. To establish methadone as a reinforcer, a fading
      procedure was used in which responding was first maintained by solutions of
      methadone (0.00625-0.4 mg/ml) combined with ethanol (0.0325-2.0% w/v).
      Subsequently, the concentration of the ethanol in the combination was gradually
      reduced to zero. Methadone-maintained responding (0.4 mg/ml) persisted when
      ethanol was no longer present. To confirm that the drug was serving as a
      reinforcer, the dose was varied: (a) by changing the volume delivered while the
      concentration was held constant and (b) by changing the concentration of the
      methadone while the volume per delivery was held constant. Over a wide range of
      doses, deliveries of methadone solution usually exceeded deliveries of
      concurrently available water. Orderly relationships were observed among methadone
      dose, response rate, and drug intake. The study of oral self-administration of
      opioid drugs by nonhuman primates may be a useful strategy for the development
      and evaluation of new drug substitution or replacement therapies.

PMID- 8741935
TI  - Mianserin markedly and selectively increases extracellular dopamine in the
      prefrontal cortex as compared to the nucleus accumbens of the rat.
AB  - The atypical antidepressant mianserin, administered at doses of 1, 5 and 10 mg/kg
      SC, dose-dependently increased up to about 6 times extracellular dopamine in the
      medial prefrontal cortex of the rat, as estimated by vertical concentric
      microdialysis probes. Mianserin failed to modify extracellular dopamine in the
      nucleus accumbens. Mianserin also dose-dependently increased extracellular
      noradrenaline in the prefrontal cortex. Yohimbine, an alpha2 antagonist,
      increased extracellular dopamine in the prefrontal cortex but the maximal
      increase was lower than that elicited by mianserin. Yohimbine also increased
      extracellular noradrenaline in the prefrontal cortex, but to a lesser extent than
      dopamine. Clonidine, an alpha2 antagonist, decreased extracellular dopamine and
      noradrenaline in the prefrontal cortex but failed to affect extracellular
      dopamine in the nucleus accumbens. Ritanserin, a 5HT2 antagonist, at doses of 1.0
      mg/kg, failed to increase extracellular dopamine in the prefrontal cortex, but
      significantly potentiated the increase in extracellular noradrenaline due to
      yohimbine. Ritanserin failed to potentiate the increase in extracellular
      noradrenaline elicited by yohimbine in the prefrontal cortex. The results are
      interpreted to indicate that mianserin increases extracellular DA as a result of
      the concurrent blockade of alpha2 and 5HT2 receptors. Failure to affect
      extracellular dopamine in the nucleus accumbens is explained as due to the lack
      of a significant effect of alpha2 and 5HT2 tone on DA release in the nucleus
      accumbens as compared to the prefrontal cortex. The results are consistent with
      the postulated relationship between antidepressant drug action and the ability to
      increase extracellular dopamine in the prefrontal cortex.

PMID- 8741934
TI  - The CCKB antagonist PD-134,308 facilitates rewarding effects of endogenous
      enkephalins but does not induce place preference in rats.
AB  - The interaction between cholecystokinin and endogenous opioid systems on
      rewarding responses was examined. Motivational effects induced by peripheral
      administration of a complete inhibitor of enkephalin catabolism, RB 101 or the
      CCKB antagonist PD-134,308, and by both compounds in combination were evaluated
      in the conditioned place preference test in rats. RB 101 (5, 10, 20, 40 and 80
      mg/kg, IP, and 20 mg/kg, IV) given alone produced a bell-shaped dose-effect
      function. A significant increase of the preference for the drug-associated
      compartment was only observed at doses of 10 and 20 mg/kg (IP). The effect
      observed with morphine was stronger, and all the doses used of this compound
      (1.25, 2.5 and 5 mg/kg, SC) were found to be active. These results suggest that
      the inhibitor of enkephalin catabolism has weak rewarding properties.
      Pretreatment with the CCKB antagonist PD-134,308 (0.1, 0.3, 1 and 3 mg/kg, IP)
      alone failed to produce a reliable aversion or preference on the paradigm
      studied. When PD-134,308 (0.3 mg/kg, IP) was coadministered with a subthreshold
      dose of morphine (0.6 mg/kg, SC) or RB 101 (5 mg/kg, IP), a conditioned place
      preference was observed, indicating that the CCKB antagonist facilitated the
      motivational responses induced by endogenous enkephalins as compared to morphine.
      This suggests that endogenous cholecystokinin, acting through CCKB receptors,
      modulates the rewarding effects of endogenous enkephalins.

PMID- 8741936
TI  - Devazepide, a CCKA receptor antagonist, impairs the acquisition of conditioned
      reward and conditioned activity.
AB  - Cholecystokinin (CCK) is co-localized with dopamine (DA) in portions of the
      mesolimbic system, where it may facilitate the function of DA through the CCKA
      receptor subtype. DA has been implicated in the acquisition of conditioned
      incentive learning, raising the possibility of a role for endogenous CCK in this
      learning process. This hypothesis was tested using two complementary behavioral
      paradigms. Experiment 1 examined the effects of systemic administration of the
      CCKA receptor selective antagonist, devazepide (0, 0.001, 0.01, 0.1 mg/kg), on
      the acquisition of conditioned reward. Two novel levers were presented to drug
      free animals in a test session; depression of the conditioned reward (CR) lever
      produced a light-tone stimulus previously paired with food availability while
      depression of the non-CR lever produced no programmed consequence. Animals
      receiving vehicle pretreatment in the food-CS conditioning sessions responded
      more frequently on the CR lever during the test session. However, pre-treatment
      with devazepide (0.1 mg/kg but not 0.001 or 0.01 mg/kg) in the conditioning
      sessions blocked the acquisition of conditioned reward. In contrast, experiment 2
      showed that the development of conditioned reward was not affected by similar
      administration of the CCKB selective antagonist, L-365,260 (0, 0.001, 0.01, or
      0.1 mg/kg). The possibilities that devazepide (0.1 mg/kg) impaired the
      development of conditioned reward by decreasing the amount of food consumed or by
      inducing a conditioned taste aversion to the food were ruled out in experiments 3
      and 4. The effects of devazepide on the acquisition of conditioned activity
      induced by amphetamine were assessed in experiment 5. During four conditioning
      sessions, rats received devazepide (0, 0.001, 0.01, 0.1 or 1.0 mg/kg) treatment
      prior to amphetamine-environment pairings. The conditioned activity effect was
      demonstrated if on the subsequent drug-free test day the environment alone
      elicited increased locomotion. Devazepide (0.1 or 1.0 mg/kg) attenuated the
      development of conditioned activity. Together, these results provide converging
      evidence that intact CCKA function may be necessary for the development of
      conditioned incentive learning.

PMID- 8741937
TI  - Dose-dependent characterization of the rewarding and stimulant properties of
      cocaine following intraperitoneal and intravenous administration in rats.
AB  - Dose-dependent differences in the rewarding and stimulant properties of cocaine
      administered intravenously (IV) and intraperitoneally (IP) were compared. Six 2
      day conditioning trials were conducted over consecutive days. Rats received
      cocaine and were placed into a compartment on one day of the trial, and were
      directly placed into a different compartment without drug on the other day. Rats
      were exposed to the compartments for either 20 or 40 min. The effects of cocaine
      on stimulant behaviors, including locomotion and stereotypies, were compared
      following the first and last injection. After conditioning, three tests were
      given with 1 rest day intervening each: (1) conditioned place preference (CPP)
      was measured as an increase in the amount of time animals spent in the injection
      compartment relative to the noninjection compartment when given access to both,
      (2) conditioned activity (CA) was measured as an increase in stimulant behaviors
      in cocaine-treated animals relative to saline controls following an injection of
      saline in the injection compartment and (3) context-independent sensitization was
      measured as an increase in stimulant behaviors following an injection of cocaine
      in the noninjection compartment relative to the animals' behavior following the
      first injection. Cocaine did not reliably produce sensitization of locomotion
      under any of the conditions examined. Cocaine produced sensitization of
      headbobbing that was more robust following IP administration than it was
      following IV administration. In both cases, sensitization of headbobbing involved
      a context-independent component. Cocaine produced CPP and CA with both routes of
      administration. CPP was established more readily with 40-min relative to 20-min
      exposures following IV administration, whereas CA was more prevalent with 20-min
      relative to 40-min exposures. This study provides a thorough characterization of
      the behavioral effects of cocaine administered IV and a new efficient method for
      assessing the effects of cocaine on conditioned and unconditioned behaviors
      following repeated administration.

PMID- 8741938
TI  - Preference for diazepam, but not buspirone, in moderate drinkers.
AB  - The purpose of the present study was to determine the preference for buspirone,
      an anxiolytic predicted to have minimal abuse potential, in comparison with
      diazepam in moderate drinkers. Preference for diazepam and buspirone was assessed
      in 55 moderate drinkers using a seven-session procedure consisting of four
      sampling sessions followed by three choice sessions. On each sampling session
      subjects ingested five capsules, one every 30 min. Color-coded capsules contained
      placebo on two sessions and drug on two sessions. Each drug capsule contained
      diazepam (4 mg) for 30 subjects and buspirone (5 mg) for 25 subjects. On choice
      sessions subjects chose whichever of the two color-coded capsules, i.e., drug or
      placebo, they wished to take. After ingesting one capsule, every 30 min they had
      the option of ingesting another capsule of the same color and content, for a
      maximum of seven capsules over the session (maximum of 28 mg diazepam or 35 mg
      buspirone). In the diazepam group 70% of subjects chose diazepam over placebo on
      at least two of the three choice sessions, whereas in the buspirone group only
      24% of subjects chose buspirone over placebo on at least two sessions. Both
      diazepam and buspirone increased measures of sedation. Only diazepam increased
      ratings of liking and impaired performance, whereas only buspirone decreased
      ratings of feeling Friendly. These results replicate previous findings indicating
      that diazepam has reinforcing effects in moderate drinkers. Further, these
      results demonstrate the pharmacological specificity of this effect by showing
      that buspirone did not function as a reinforcer under these same conditions.

PMID- 8741939
TI  - The relative salience of morphine and contextual cues as conditioned stimuli.
AB  - Two experiments were conducted to delineate further the properties of
      conditioning when morphine is used as a conditioned stimulus (CS) in the
      conditioned suppression of drinking paradigm. Experiment 1 used a test for
      overshadowing designed to compare the relative salience of contextual cues (metal
      box) and morphine induced cues (6 mg/kg, IP) as CSs when each was paired with a
      foot shock unconditioned stimulus (US) in water deprived rats. Six groups (six
      rats each) were exposed to conditioning procedures during which the conditioning
      context was present 19 h (groups 1 and 2), 90 min (groups 3 and 4), or 5 min
      (groups 5 and 6) before shock onset, and morphine (in groups 1, 3, and 5) or
      saline (in groups 2, 4, and 6) was injected 10 min before shock. Subsequently,
      the magnitude of suppression of drinking in response to morphine, to the metal
      box, and to morphine plus the metal box was measured. Only group 1 (19 h group)
      suppressed drinking in response to morphine, while groups 3-6 suppressed drinking
      whenever tested in the metal box. The results indicate that morphine cues acted
      as a CS that elicited suppression of drinking in group 1, and that contextual
      cues present up to 90 min before morphine cues overshadowed morphine. Experiment
      2 showed that expression of the conditioned response to morphine was blocked by
      naloxone.

PMID- 8741940
TI  - Effects of stimulation or blockade of central nicotinic-cholinergic receptors on
      performance of a novel version of the rat stimulus discrimination task.
AB  - This study evaluated the effects of two central nicotinic-cholinergic receptor
      agonists and an antagonist on performance accuracy of a rat, delayed stimulus
      discrimination task (DSDT). Rats were trained to discriminate between an auditory
      and visual stimulus by pressing a right or left lever. To diminish the rat's
      ability to use mediating spatial strategies to solve the task, computer
      automated, retractable doors separated the animal from the levers during delay
      intervals, thus reducing positioning at the lever. After stable baselines were
      achieved, rats were grouped and administered placebo (saline) and nicotine,
      lobeline or mecamylamine in a randomized dose series. Each group received two
      complete series of the selected compound on different occasions. Mecamylamine
      impaired DSDT accuracy in a dose-dependent manner while optimal doses of nicotine
      and lobeline significantly improved accuracy. Nicotine differed from lobeline in
      regard to its interaction with a dose of mecamylamine (1.0 mg/kg) that had not
      impaired DSDT accuracy. Combined administration of lobeline and mecamylamine was
      followed by a significantly increased level of DSDT accuracy that was similar to
      the improvement following administration of lobeline alone. In contrast, combined
      administration of nicotine and mecamylamine did not result in increased DSDT
      accuracy. Furthermore, lobeline administration similarly improved accuracy of
      trials associated with both the light and the tone, while nicotine improved
      accuracy of trials associated with the light to a much greater degree. These data
      suggest that the increases in DSDT accuracy associated with lobeline may be
      expressed through non-nicotinic mechanisms or a nicotinic receptor which is not
      blocked by mecamylamine.

PMID- 8741941
TI  - Serotonin reuptake inhibitors reduce conditioned fear stress-induced freezing
      behavior in rats.
AB  - Conditioned fear stress (CFS)-induced freezing behavior has been proposed as an
      animal model of anxiety. In the present study, freezing was used to determine the
      anxiolytic activity of selective serotonin reuptake inhibitors (SSRIs), which are
      reported to be clinically effective in anxiety disorders. The duration of
      freezing behavior was reduced by acute treatment with the SSRIs citalopram (1-10
      mg/kg) and fluvoxamine (3-30 mg/kg). Acute treatment with the serotonin (5
      HT)/noradrenaline (NA) mixed reuptake inhibitor milnacipran (3-30 mg/kg) also
      attenuated CFS-induced freezing, while acute treatment with the NA reuptake
      inhibitors maprotiline and ORG4428, and the dopamine (DA) reuptake inhibitor
      GBR12909 failed to alter CFS-induced freezing. These results indicate that
      facilitation of 5-HT availability in the brain produced by 5-HT reuptake
      inhibition reduces CFS-induced freezing behavior. CFS may be a useful model for
      detecting the anxiolytic potential of 5-HT reuptake inhibitors.

PMID- 8741942
TI  - Effect of NMDA receptor antagonists on D1, D2 and D1/D2 mediated behaviors in
      intact rats.
AB  - The effect of treatment with the competitive (CGP 43487) and non-competitive (MK
      801) NMDA antagonists on behaviors induced by the stimulation of D1 (SKF 38393
      induced grooming), D2 (LY 171555 elicited hypermotility) or D1/D2 (apomorphine
      induced locomotion and stereotypies) was observed in intact rats. The
      administration of low doses of MK-801 (0.03 and 0.06 mg/kg) or CGP 43487 (0.375
      and 0.75 mg/kg), which were without effect by themselves on animal locomotion,
      reduced the hyperactivity induced by LY 171555 (0.15 mg/kg) and did not change
      the stimulating motor effect of a low dose of apomorphine (0.15 mg/kg).
      Spontaneous grooming behavior was inhibited by both NMDA antagonists, whereas the
      administration of CGP 43487 but not of MK-801 potentiated grooming response to
      SKF 38393 (10 mg/kg). Both antagonists increased stereotyped behavior induced by
      0.25 mg/kg apomorphine. The results, according to those obtained by other authors
      in DA depleted/lesioned animals, support the view of interaction between
      NMDA/D1,D2 receptors in intact rats.

PMID- 8741943
TI  - Differential responsiveness of inbred strains of rats to antidepressants in the
      forced swimming test: are Wistar Kyoto rats an animal model of subsensitivity to
      antidepressants?
AB  - In three experiments we have studied the effects of acute administration of
      various doses (5, 10, 15 and 25 mg/kg) of desipramine (DMI) and two doses (0.5
      and 2 mg/kg) of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective
      5HT1A receptor agonist, on behaviour of five inbred strains of rats in the
      holeboard and the forced swimming test (FST). The strains were Brown-Norway (BN),
      Fischer 344 (FIS), Lewis (LEW), Spontaneously Hypertensive Rats (SHR) and Wistar
      Kyoto (WKY). In drug-free conditions, the strains showed striking differences in
      their activity in the holeboard and in the FST, the WKY rats being the most
      passive in both tests. The dose of 15 mg/kg DMI caused a profound inhibitory
      effect on locomotor/exploration activity in all strains. In the FST, this dose of
      DMI increased struggling and reduced immobility in BN, FIS and LEW rats, but did
      not exert any effect in SHR and WKY rats. The lack of marked strain-dependent
      differences in the sensitivity to the inhibitory effects of DMI on locomotor
      activity or exploration rule out a major role of changes in the metabolism of
      drug among strains as an explanation for differential response to DMI in the FST.
      In further experiments three strains were used: BN (responsive), WKY (non
      responsive) and the outbred Sprague Dawley (SD) rats. In the FST, both DMI and 8
      OH-DPAT, at all doses, decreased immobility and increased struggling in BN and SD
      rats. However, WKY rats responded only to a very high dose of DMI (25 mg/kg).
      Hence, WKY rats are not only passive in the FST, but are also subsensitive to
      acute antidepressant administration. The present data indicate that the levels of
      activity of animals in the FST in drug-free conditions are not predictive of
      their response to antidepressants, and that inbred strains might be useful for
      studying the biological basis of subsensitivity to antidepressants and depressive
      like behaviour.

PMID- 8741944
TI  - Evidence for genetically mediated dysfunction of the central dopaminergic system
      in the stargazer rat.
AB  - The stargazer rat is an autosomal recessive mutant (homozygous stg/stg) that
      displays abnormal behavior, characterized by stereotypic head-movement, circling,
      and a high level of ambulatory activity. Heterozygous (stg/+) littermates display
      normal spontaneous behaviors. In this study, stargazers and their unaffected
      littermates were compared in their behavioral responses to both stimulation and
      inhibition of dopamine D2/D3 receptors, using quinpirole and haloperidol.
      Stargazers were observed to yawn a significantly fewer number of times than
      littermates in response to (--)-quinpirole (50 mu g/kg, IP). Haloperidol (HAL 0.1
      mg/kg and 0.3 mg/kg, SC) caused a decrease in stereotypic head-movement in the
      mutants that was both time- and dose-dependent. In normal littermates, HAL
      inhibited locomotor activity and produced catalepsy in a time- and dose-dependent
      manner. In stargazers, both doses of HAL inhibited locomotor activity to a
      similar degree as in the littermates. However, no catalepsy was detectable in the
      mutants using 0.1 mg/kg of HAL. A dose of 0.3 mg/kg HAL was only weakly
      cataleptogenic. Overall, the spectrum of abnormal behaviors expressed by the
      stargazers and the present evidence of D2/D3 receptor subsensitivity suggest that
      stargazers possess a genetically mediated dysfunction of the central dopaminergic
      system.

PMID- 8741945
TI  - Movements in never-medicated schizophrenics: a preliminary study.
AB  - Descriptions of schizophrenia dating to the beginning of this century include
      mention of abnormal movements which are similar to tardive dyskinesia (TD),
      currently thought to be sequelae of neuroleptic medication. In order to examine
      the extent to which such movements might appear in the normal course of
      schizophrenia, we examined a sample of 22 never-medicated DSM-III-R
      schizophrenics who presented for treatment at a psychiatric center in Casablanca,
      Morocco. Duration of illness in this sample ranged from 1 to 10 years. Patients
      were assessed for choreoathetoid movements using the Abnormal Involuntary
      Movement Scale (AIMS). Videotaped and live examinations were rated by the
      investigators. Three patients (14%) met research diagnostic criteria for probable
      SD. Mild movements in one body part (AIMS = 2) were seen in an additional five
      (23%) patients. The movements were characteristic of TD, although their somatic
      distribution differed from previous studies. Total AIMS score increased with age
      and duration of illness (r = 0.64, P < 0.01). These findings suggest that
      choreoathetoid movements may appear spontaneously in patients with schizophrenia.

PMID- 8741946
TI  - Amphetamine and negative symptoms of schizophrenia.
AB  - The purpose of this study was to assess further the effect of amphetamine on
      negative symptoms of schizophrenia. Thirty-seven schizophrenic males meeting DSM
      III criteria were rated with the Brief Psychiatric Rating Scale, the Abrams and
      Taylor Scale, and the Abnormal Involuntary Movements Scale before and after
      double-blind administration of either amphetamine (n = 26) or placebo (n = 11).
      Our results indicated that amphetamine administration generally did not improve
      negative symptoms, even when accounting for changes in positive symptoms.
      However, greater baseline negative symptoms were associated with a modest
      diminution after amphetamine treatment. Therefore, amphetamine may modestly
      improve negative symptoms in those schizophrenics in whom this symptomatology is
      more severe.

PMID- 8741947
TI  - Effects of kappa receptor agonists on D1 and D2 dopamine agonist and antagonist
      induced behaviors.
AB  - Striatal dynorphin-containing neurons receive dopaminergic inputs from the
      substantia nigra pars compacta and project primarily to the substantia nigra pars
      reticulata and entopeduncular nucleus. These neurons mainly express dopamine (DA)
      D1 receptors and thus dynorphin system stimulation might be expected largely to
      influence D1 receptor agonist or antagonist effects on motor function. It is well
      known the interaction existing between DA D1 and D2 drugs in the induction of
      behavioral effects. However, the effects of dynorphin on selective D1 and D2 DA
      agonist and antagonist-induced behaviors have not yet been investigated.
      Administration of the kappa agonists spiradoline (0.5, 1 and 5 mg/kg) or U50,488H
      (1, 10 and 25 mg/kg) decreased non-stereotyped grooming induced by the selective
      D1 agonist SKF38393. This effect was inhibited by the non-selective opioid
      receptor antagonist naloxone (20 mg/kg) and by the selective kappa antagonist nor
      binaltorphimine (nor-BNI, 20 mg/kg). Stereotypies induced by the selective D2
      agonist quinpirole were decreased by spiradoline (1 and 5 mg/kg) and by U50,488H
      (1, 10 and 25 mg/kg), while jerking movements of a type associated with increased
      D2 receptor and decreased D1 receptor stimulation emerged. Kappa agonist effects
      were inhibited by the prior administration of SKF38393 (10 mg/kg); these
      inhibitory effects were blocked by prior administration of the D1 antagonist
      SCH23390 (5 mg/kg). Naloxone reversed the effects of both kappa agonists on
      quinpirole-induced stereotypies. Kappa agonists increased D1 antagonist-induced
      catalepsy, but had no effect on D2 antagonist-induced catalepsy. Naloxone and nor
      BNI inhibited this effect. These results suggest that the motoric effects of D1
      receptor antagonists in part reflect stimulation of striatal dynorphin containing
      efferents.

PMID- 8741949
TI  - Effects of scopolamine on learning and memory in monkeys.
AB  - The effects of scopolamine were evaluated in monkeys responding under operant
      procedures designed to evaluate drug effects on learning and memory. In one
      procedure, responding was maintained by food presentation under a multiple
      schedule. One component of the multiple schedule was a repeated-acquisition task
      in which the discriminative stimuli for left- and right-key responses changed
      each session (learning). In the other component, the discriminative stimuli for
      responses were the same each session (performance). In both components of the
      multiple schedule, scopolamine produced dose-related decreases in responding;
      there was little evidence of differential rate-decreasing effects between
      components. Percent errors in learning were increased in a dose-related manner,
      whereas percent errors in performance were generally unaffected except at high
      doses, which also produced substantial decreases in response rate. These results
      suggest that acquisition is more sensitive to the disruptive effects of
      scopolamine than is performance. The second procedure utilized repeated
      acquisition and delayed performance as a technique to study the effects of
      scopolamine on memory. In this procedure, each session was divided into three
      phases: acquisition, delay and performance. After a 24-h delay, scopolamine had
      little or no effect on retention, accuracy or rate of responding. In contrast,
      after a 60-min delay, scopolamine decreased retention in a dose-related manner.
      These data suggest that scopolamine produces a greater disruptive effect on short
      (60-min) versus long (24-h) delays.

PMID- 8741948
TI  - Alcohol pretreatment increases preference for cocaine over monetary
      reinforcement.
AB  - Non-dependent cocaine users participated in a two-phase experiment conducted
      under controlled laboratory conditions. During phase 1, subjects sampled
      intranasal cocaine (100 mg) and placebo (96 mg lactose + 4 mg cocaine) in
      separate sessions and under double-blind conditions. Sampling sessions were
      followed by a single choice session in which subjects made a maximum of ten
      choices between 10 mg unit doses of cocaine or placebo. Only subjects who
      reliably (> or = 70%) chose cocaine over placebo in phase 1 participated in phase
      2. During phase 2, subjects participated in a series of nine experimental
      sessions conducted on different days in which they were pretreated with varying
      doses of alcohol (placebo, 0.5, and 1.0 g/kg) and made a maximum of ten choices
      between 10 mg unit doses of cocaine and an alternative reinforcer (i.e., varying
      amounts of money). Visual-analog ratings of drug effects and cardiac function
      were monitored across all experimental sessions. Cocaine was reliably chosen over
      placebo by the majority (9 of 11) of subjects during phase 1, demonstrating that
      the drug functioned as a reinforcer. During phase 2, alcohol pretreatment
      significantly increased choice of cocaine over the alternative reinforcer, while
      increasing monetary value decreased cocaine choice. Ratings on some visual-analog
      scales (e.g., good effects) paralleled cocaine choice, with alcohol pretreatment
      increasing ratings and greater monetary value decreasing them. Cardiac output
      increased above baseline levels across all alcohol and monetary conditions, but
      maximal effects were observed during sessions involving pretreatment with the
      active alcohol doses. Overall, these results demonstrate (a) that alcohol can
      increase preference for cocaine over alternative reinforcers and thereby may
      thwart efforts to reduce or abstain from cocaine use, (b) that availability of an
      alternative, non-drug reinforcer can effectively decrease preference for cocaine,
      and (c) that combined use of alcohol and cocaine increases cardiac risk compared
      to use of cocaine alone.

PMID- 8741950
TI  - Enhancement of cocaine's abuse liability in methadone maintenance patients.
AB  - The present study was conducted to determine whether methadone maintenance alters
      the pharmacodynamic effects of single doses of cocaine. Twenty-two current users
      of IV cocaine who were not seeking treatment for their illicit cocaine use
      participated while living on a research unit. Eleven were maintained on methadone
      50 mg PO daily as treatment for their opioid abuse; 11 were opioid abusers who
      were not physically dependent on opioids and who provided opioid-free urines
      throughout the study. Each subject received acute cocaine challenge doses of 0,
      12.5, 25, and 50 mg intravenously in random order under double-blind conditions
      in separate test sessions. Physiologic and subject-rated responses were measured
      before injection and for 2 h after. In the methadone maintenance group, cocaine
      challenge sessions occurred 15.5 h after the daily methadone dose. There were
      significant differences between the methadone-dependent and nondependent groups:
      1) baseline differences related to chronic methadone administration and not
      associated with cocaine administration (lower respiration rates and pupil
      diameter; higher skin temperature) and 2) differences in response to cocaine
      administration; cocaine-induced increases in subject ratings of Drug Effect,
      Rush, Good Effects, Liking, and Desire for Cocaine and in heart rate were greater
      in the methadone maintenance patients compared to the non-dependent group. These
      results indicate that the positive subjective effects and some physiological
      effects of cocaine are enhanced in methadone-maintained individuals, suggesting a
      pharmacological basis for the high rates of cocaine abuse among methadone
      maintenance patients.

PMID- 8741952
TI  - Effects of drug history on the acquisition of responding maintained by GBR 12909
      in rhesus monkeys.
AB  - The reinforcing effects of cocaine have been associated with its actions at the
      dopamine reuptake site. Previous studies have shown that selective dopamine
      reuptake inhibitors can attenuate cocaine self-administration in animals,
      suggesting that they may serve as pharmacotherapeutic agents. In order to assess
      the potential reinforcing effects of one of these agents, the acquisition and
      maintenance of GBR 12909 self-administration were studied in different groups of
      rhesus monkeys (Macaca mulatta) that were either experimentally naive or
      experienced with respect to the self-administration of cocaine or GBR 12909.
      Lever-pressing was maintained under a multiple FR30 schedule with alternating
      components of either food or drug presentation. Experimentally naive monkeys
      failed to self-administer low doses of GBR 12909 (3-30 mu g/kg per injection).
      However, after a history of cocaine self-administration, GBR 12909 (56 mu g/kg
      per injection and then 30 mu g/kg per injection) maintained numbers of drug
      deliveries similar to those maintained by cocaine. When another group of
      experimentally-naive monkeys was initially exposed to GBR 12909 self
      administration, 56 mu g/kg per injection failed to maintain responding. However,
      subsequent exposure to 100 mu g/kg per injection established GBR 12909 self
      administration, and high levels of responding were sustained later when the unit
      dose was decreased to 30 mu g/kg per injection. In monkeys with prior experience
      with cocaine self-administration (approximately 75 sessions) unit doses of either
      30 mu g/kg per injection or 56 mu g/kg per injection GBR 12909 maintained
      responding. In another group of monkeys with a more extensive history of cocaine
      self-administration (approximately 320 sessions), unit doses of either 10 mu g/kg
      per injection or 30 mu g/kg per injection GBR 12909 maintained responding. These
      results show that drug-maintained responding can be established with higher unit
      doses of GBR 12909. After exposure to these higher, more effective doses of GBR
      12909, or effective doses of cocaine, lower doses of GBR 12909 are more likely to
      support drug-maintained responding.

PMID- 8741951
TI  - Temporal relationships between the pharmacokinetics of methylphenidate in the
      human brain and its behavioral and cardiovascular effects.
AB  - Positron emission tomography was used to compare the pharmacokinetics of
      [11C]methylphenidate in the human brain with the temporal course of the
      subjective and cardiovascular effects observed after intravenous methylphenidate
      (0.5 mg/kg). Four subjects were tested twice with [11C]methylphenidate, at
      baseline and after methylphenidate. All subjects showed almost identical uptake
      of 11C labeled drug in brain, as well as a very similar decrease in binding of
      [11C]methylphenidate in basal ganglia, after pretreatment with methylphenidate.
      In contrast, the magnitude of the behavioral and cardiovascular changes induced
      by methylphenidate varied among the subjects. The temporal course for
      methylphenidate effects paralleled closely the pharmacokinetics of
      [11C]methylphenidate in brain for the perception of "restlessness" and for
      changes in systolic blood pressure and heart rate. In contrast, methylphenidate
      induced "high", "anxiety" and changes in diastolic blood pressure decreased
      rapidly despite long lasting binding of the drug in brain. These results indicate
      that binding of methylphenidate in brain does not appear to predict individual
      responses to the drug and that more than one neurotransmitter and/or adaptation
      process are likely to be involved in the behavioral and cardiovascular effects of
      methylphenidate.

PMID- 8741953
TI  - Circadian rhythm in the response of central 5-HT1A receptors to 8-OH-DPAT in
      rats.
AB  - Circadian rhythm in the behavioral responsiveness to the selective 5-HT1A
      receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was studied
      in rats. Rats were subcutaneously injected with 8-OH-DPAT at one of the following
      times of day: 0000, 0400, 0800, 1200, 1600, 2000 hours. The post-synaptic 5-HT1A
      receptor behavioral syndrome, that is, forepaw treading, head weaving, and flat
      body posture, were measured after the administration of 8-OH-DPAT. Circadian
      rhythms were found in each of the behavioral responses to 8-OH-DPAT. Peak
      responses were observed in the mid-dark phase (1200 hours) while the weakest
      responses were observed in the mid-light phase (0000 hours). In a subsequent
      experiment, 8-OH-DPAT was administered intracerebroventricularly during the mid
      dark phase and the mid-light phase. The behavioral responses to the drug in the
      mid-dark phase were significantly higher than those in the mid-light phase. These
      results suggest that the function of central postsynaptic 5-HT1A receptor
      exhibits circadian rhythm.

PMID- 8741954
TI  - Reversal of overshadowing in a drug mixture discrimination in rats.
AB  - Previous studies have suggested that in some circumstances, learning processes
      such as overshadowing may determine the effects that one drug has upon the
      response to another. The experiments described here examined overshadowing in
      rats trained to discriminate mixtures of nicotine plus midazolam in two-lever
      operant procedures with food reinforcement. After training for 60 sessions,
      midazolam (0.32 mg/kg SC) overshadowed nicotine (0.32 mg/kg SC) so that the
      discriminative stimulus effect of nicotine seen in control rats trained with
      nicotine alone was abolished (n = 8-10). In the next phase of the study, the
      discriminative response to midazolam in one group of mixture-trained rats was
      devalued by means of an extinction procedure which weakened the relationship
      between administration of midazolam and the response that was reinforced. Dose
      response determinations then showed that the devaluation procedure had indeed
      attenuated the response to midazolam, whereas the previously overshadowed
      response to nicotine was restored. Post-session injections of drugs were used to
      equate the pharmacological histories of the groups and the effects seen were
      therefore attributable to training with the drugs and not simply to repeated
      exposure to them. Additionally, in the control rats trained with nicotine only
      (with midazolam given post-session), midazolam markedly reduced response rates,
      whereas in the three groups of rats trained with the mixture, midazolam had
      little response rate-depressant effect; this observation suggests that
      behaviourally contingent tolerance had developed to the response rate-reducing
      effect of midazolam. Application of devaluation procedures in studies of the
      discriminative stimulus effects of single drugs with multiple effects may provide
      a means for manipulating the characteristics of the discriminations obtained and
      for identifying individual elements of the drug-produced stimulus complex.

PMID- 8741955
TI  - Nicotine effects on adults with attention-deficit/hyperactivity disorder.
AB  - Several lines of evidence suggest that nicotine may be useful in treating the
      symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). The current study
      was an acute, placebo-controlled double-blind experiment to determine whether
      nicotine might be useful as an alternative treatment of adults with ADHD
      symptomatology. Six smokers and 11 nonsmokers who were outpatient referrals for
      ADHD were diagnosed by DSM-IV criteria. Measures of treatment effect included the
      Clinical Global Impressions (CGI) scale, Hopkins' symptom check list (SCL-90-R),
      the Profile of Mood States (POMS), Conners' computerized Continuous Performance
      Test (CPT), the Stroop test, and an interval-timing task. The smokers underwent
      overnight deprivation from smoking and were given a 21 mg/day nicotine skin patch
      for 4.5 h during a morning session. The nonsmokers were given a 7 mg/day nicotine
      skin patch for 4.5 h during a morning session. Active and placebo patches were
      given in a counter-balanced order approximately 1 week apart. Nicotine caused a
      significant overall nicotine-induced improvement on the CGI. This effect was
      significant when only the nonsmokers were considered, which indicated that it was
      not due merely to withdrawal relief. Nicotine caused significantly increased
      vigor as measured by the POMS test. Nicotine caused an overall significant
      reduction in reaction time (RT) on the CPT, as well as, with the smokers, a
      significant reduction in another index of inattention, variability in reaction
      time over trial blocks. Nicotine improved accuracy of time estimation and lowered
      variability of time-estimation response curves. Because improvements occurred
      among nonsmokers, the nicotine effect appears not to be merely a relief of
      withdrawal symptoms. It is concluded that nicotine deserves further clinical
      trials with ADHD.

PMID- 8741956
TI  - Adenosine receptor agonists attenuate and adenosine receptor antagonists
      exacerbate opiate withdrawal signs.
AB  - Previous studies have demonstrated a role for adenosine in mediating opiate
      effects. Adenosine receptors and their functions have been shown to be regulated
      by chronic opiate treatment. This study examines the role of adenosine receptors
      in the expression of opiate withdrawal behaviors. The effects of single doses of
      parenterally administered adenosine receptor subtype-selective agonists and
      antagonists on opiate withdrawal signs in morphine-dependent mice were measured.
      Mice received subcutaneous morphine pellet treatment for 72 h and then underwent
      naloxone-precipitated withdrawal after pretreatment with adenosinergic agents.
      Adenosine agonists attenuated different opiate withdrawal signs. The A1 agonist R
      N6(phenylisopropyl)adenosine (0, 0.01, 0.02 mg/kg, IP) significantly reduced wet
      dog shakes and withdrawal diarrhea, while the A2a-selective agonist 2-p-(2
      carboxethyl)phenylethylamino-5'-N-ethylcarboxamido adenosine or CGS 21680 (0,
      0.01, 0.05 mg/kg, IP) significantly inhibited teeth chattering and forepaw
      treads. Adenosine receptor antagonists enhanced different opiate withdrawal
      signs. The adenosine A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine (0, 1, 10
      mg/kg, IP) significantly increased weight loss and the A2 antagonist, 3,7
      dimethyl-1-propargylxanthine (0, 1 and 10 mg/kg, IP) enhanced wet dog shakes and
      withdrawal diarrhea. Treatment effects of adenosinergic agents were not due to
      nonspecific motor effects, as demonstrated by activity monitoring studies. These
      results support a role for adenosine receptors in the expression of opiate
      withdrawal and suggest the potential utility of adenosine agonists in its
      treatment.

PMID- 8741957
TI  - Effects of morphine, naloxone and their interaction in the learned-helplessness
      paradigm in rats.
AB  - The aim of this study was to investigate the possible involvement of the mu
      opioid system on the learned-helplessness paradigm, an experimental model of
      depression, in rats. In this test, rats were first exposed to inescapable foot
      shocks (IS); 48 h later, they were submitted to a daily shuttle-box session (30
      trials) for 3 consecutive days. Avoidance responses, escape failures and animal
      activity during each intertrial interval were recorded. Twice daily injections of
      morphine (0.25-8 mg/kg per day, SC), a mu-opioid agonist, reduced the increased
      escape failures induced by IS, as did tricyclic antidepressants. Significantly
      higher intertrial activity was observed in rats treated with morphine (2-8 mg/kg
      per day) compared with their associated control groups. Naloxone (1 and 2 mg/kg,
      IP), a mu-opioid antagonist, injected 10 min before each shuttle-box session
      impaired escape behavior in non-stressed rats and worsened the escape deficit
      induced by IS. Morphine-induced improvement of escape behavior and increase in
      intertrial activity were clearly reversed by a low inactive dose of naloxone (0.5
      mg/kg). These results suggest that mu-opioid receptor mediation is involved in
      the deleterious effects of uncontrollable stress.

PMID- 8741958
TI  - Smoked cocaine self-administration in females.
AB  - Although approximately 32% of all smoked cocaine ("crack") users are women, most
      studies investigating cocaine use have recruited only male subjects. Therefore,
      this study examined the smoked cocaine self-administration patterns of female
      crack abusers. A work requirement, where up to five tokens were earned by
      subjects, was followed by the administration of a sample delivery of one of three
      dose sizes [5.0 mg (placebo), 0.2 mg/kg, 0.4 mg/kg] of cocaine. The three dose
      sizes of cocaine were administered in counterbalanced order across subjects, with
      each subject receiving one dose size within a session and all dose sizes across
      the three experimental sessions. A self-administration phase followed the sample
      delivery, during which a token could be exchanged every 30 min for monetary
      reimbursement or a delivery of cocaine in the same dose size as the sample
      delivery. The results show that females' patterns of behavioral and subjective
      responding to smoked cocaine exhibit clear dose-related effects, thus affirming
      this self-administration model as safe and appropriate for use with women.

PMID- 8741959
TI  - Acute and chronic nicotine effects on working memory in aged rats.
AB  - Acute and chronic nicotine administration has been repeatedly been found in our
      laboratory to improve working memory performance of normal adult rats in the
      radial-arm maze. The current study was conducted to determine if acute or chronic
      nicotine administration would improve working memory performance in aged rats.
      Sixteen young adult (3-7 months) and 32 aged (24-28 months) male Sprague-Dawley
      rats were trained on an eight-arm radial maze. A significant age-related choice
      deficit was seen during the 21 sessions of training. After training, half of the
      rats in each age group were implanted with nicotine-containing osmotic minipumps
      and the other half implanted with vehicle-containing pumps. Consistent with
      previous work, the young adult rats given chronic nicotine (approximately 5 mg/kg
      per day as measured as nicotine base) showed a significant improvement in working
      memory performance. In contrast, the aged rats did not show a significant effect
      of this dose of chronic nicotine. After a 2 week withdrawal period the remaining
      rats underwent a series of acute drug challenges with nicotinic and muscarinic
      agonists and antagonists as well as the dopaminergic antagonist haloperidol.
      Mecamylamine and haloperidol impaired the memory performance of the young adult
      rats, whereas the aged rats showed no effect. In contrast, scopolamine impaired
      performance of both young adult and aged rats in a similar manner. Both
      pilocarpine and nicotine improved the memory performance of the aged rats, but
      did not improve the young adult rats, possibly due to a ceiling effect on
      performance. During the cholinergic agonist drug phase, the aged rats which had
      previously been given chronic nicotine infusions showed better performance than
      those which had not. The resistance of the aged rats to chronic nicotine-induced
      working memory improvements and acute mecamylamine-induced working memory
      deficits may have resulted from the decline in nicotinic receptors seen with
      aging. Chronic co-administration of the nicotinic antagonist mecamylamine in a
      previous study was found to abolish the chronic nicotine-induced working memory
      improvement. The aged rats were resistant to haloperidol-induced deficits which
      may have resulted from the decrease in dopaminergic receptors seen with aging.
      Interestingly, acute cholinergic agonists including nicotine did improve working
      memory performance in the aged rats and previous chronic nicotine infusion was
      beneficial during the period of acute cholinergic agonist challenge. This
      suggests that nicotinic treatment may be of use for treating age associated
      memory impairments but that special dosing regimens may be required.

PMID- 8741960
TI  - Potentiation of the effects of raclopride on sucrose consumption by the 5-HT2
      antagonist ritanserin.
AB  - We examined the effects on sucrose consumption of a dopamine (DA) D2/D3
      antagonist (raclopride, 0-0.3 mg/kg), a serotonin 5-HT2/2c antagonist
      (ritanserin, 0-0.4 mg/kg), and raclopride (0.15 mg/kg) combined with ritanserin
      (0-0.4 mg/kg). Three different concentrations of sucrose solution (0.7%, 7.0% and
      34%) were tested. The concentration-intake function in drug-free rats was an
      inverted-U, with 7.0% sucrose supporting the highest intake. Raclopride (0.3
      mg/kg) inhibited intake of 7.0% sucrose, but its effect on 0.7% sucrose fell
      short of significance (P < 0.06) and intake of 34% sucrose was unchanged.
      Ritanserin did not affect sucrose intake when given on its own, but synergized
      with a previously ineffective dose of raclopride (0.15 mg/kg) so as to cause a
      significant inhibition of 7.0% sucrose intake and increase in 34% sucrose intake.
      These data indicate that 5-HT2 antagonism potentiated the behavioural effects of
      raclopride and we speculate that this interaction might contribute to the
      efficacy of atypical neuroleptic drugs.

PMID- 8741961
TI  - Effect of destruction of the 5-hydroxytryptaminergic pathways on the acquisition
      of temporal discrimination and memory for duration in a delayed conditional
      discrimination task.
AB  - This experiment examined the effect of destruction of the ascending 5
      hydroxytryptaminergic (5HTergic) pathways on the acquisition of a temporal
      discrimination and on memory for duration, using a delayed conditional
      discrimination task. In phase I, rats that had received injections of 5,7
      dihydroxytryptamine into the dorsal and median raphe nuclei, and sham-lesioned
      control rats, were trained in a series of discrete trials to press lever A
      following a 2-s presentation of a light stimulus, and lever B following an 8-s
      presentation of the same stimulus. Following stimulus offset, a response on a
      panel placed midway between the two levers was required in order to initiate
      lever presentation; a single response on either lever resulted in withdrawal of
      both levers and, in the case of a "correct" response, reinforcer delivery. Both
      groups gradually acquired accurate discrimination, achieving > 90% correct
      choices within 20-30 sessions; the lesioned group acquired accurate performance
      significantly faster than the control group. In phase II, delays were interposed
      between stimulus offset and lever presentation in 50% of the trials (2, 4, 8, 16
      and 32 s; 10% of trials in each case). Accuracy declined as a function of post
      stimulus delay in both groups, and there was no significant difference between
      the performances of the two groups. Both groups showed an increasing tendency to
      respond on lever A following longer post-stimulus delays ("choose-short" effect);
      this effect was somewhat enhanced in the lesioned group. The levels of 5HT and 5
      hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the
      levels of noradrenaline and dopamine were not altered.

PMID- 8741962
TI  - High frequency hearing loss associated with otitis media.
AB  - OBJECTIVE: Long-term effects of otitis media (OM) on hearing in both conventional
      and high frequency (HF) regions in children were studied. DESIGN: Children with
      OM were enrolled in a prospective study of sequelae after tympanostomy tube
      insertion (intubation) and were examined serially at 6-mo intervals with
      audiometry and multifrequency tympanometry, and every 3 mo with tympanometry and
      otoscopy for at least 3, and up to 5 yr. Hearing thresholds in conventional and
      HF regions were compared with those of an age-matched control group of children
      who had 2 or fewer documented episodes of any type of OM since birth. Frequency
      of OM during follow-up, number of intubations, use of ototopical eardrops, age,
      and sex along with several other factors were analyzed for a relationship to HF
      hearing loss. RESULTS: Otitis media history was associated with poorer HF
      hearing, but the presence of subtle residual middle ear dysfunction was not
      associated with an additional effect on HF hearing. Active middle ear disease
      significantly affected both conventional and HF thresholds. The number of
      intubations and frequency of OM during follow-up were significantly and
      positively associated with poorer HF thresholds. Several other factors, including
      middle ear appearance at intubation, presence of tympanosclerosis, age, male
      gender, and use of ototopical eardrops, were also associated with poorer HF
      hearing but failed to reach significance after their intercorrelation with number
      of intubations and frequency of OM was considered. CONCLUSIONS: High frequency
      hearing loss was associated with OM after middle ear disease resolved and after
      middle ear dysfunction was excluded. Relatively poorer HF hearing thresholds
      found for older children with OM histories appeared to be attributable to time
      spent with ear disease. Children at greatest risk for HF hearing loss were those
      who required multiple intubations. Older children tended to have poorer hearing
      in both conventional and HF regions, suggesting that the effects of OM on hearing
      thresholds may be progressive.

PMID- 8741963
TI  - Aging effects in multifrequency tympanometry.
AB  - OBJECTIVE: The objective of this investigation was to determine the effect of the
      aging process on various measures derived from multifrequency tympanograms.
      DESIGN: Tympanograms were recorded at 226 Hz and at one-sixth octave intervals
      from 250 through 2000 Hz from 136 adult male subjects; 20 in each decade of life
      from age 20 through age 79 and 16 older than 79 yr of age. Analyses were
      performed on two measures of resonant frequency of the middle ear, two measures
      of static admittance at 226 Hz, and tympanometric width at 226 Hz. RESULTS: No
      systematic effect of age on any of these measures was evident in this population
      except for a small, but significant, correlation between tympanometric width and
      age. Analyses of variance indicated no significant difference among mean values
      on any measure when subjects were grouped by decade of life. Values of these
      tympanometric variables are reported to add to the growing base of data from
      normal low-frequency and multifrequency tympanograms. CONCLUSIONS: The main
      finding of this investigation indicates that normative values of middle ear
      resonance, admittance, and tympanometric width obtained from groups of adults of
      various ages can be applied to elderly men.

PMID- 8741964
TI  - Immittance findings in school-aged children.
AB  - OBJECTIVE: The purpose of the present study was to obtain the median values and
      distributions of tympanometric variables and the distributions of acoustic reflex
      thresholds for three age groups of unselected school-aged children. Furthermore,
      the investigation was undertaken to provide normative immittance data for
      selected, otologically normal 7-, 10-, and 14-yr-old children. DESIGN: A total of
      687 children, aged 6 to 15 yr, were thoroughly examined clinically,
      audiometrically, and tympanometrically. The same examinations were made in 471
      otologically normal children, selected from the total population on the basis of
      the findings that both tympanic membranes were otomicroscopically healthy, and
      the hearing thresholds were better than or equal to 25 dB HL at all frequencies.
      RESULTS: The results showed that the median equivalent ear canal volume (Vec)
      increased from 0.65 ml to 1.00 ml with increasing age both in the unselected and
      selected populations. The median peak admittance values (Ytm) were between 0.55
      and 0.5 mmho in the respective study groups, somewhat higher in older than in
      younger children. The same tendency was also seen in gradient and tympanometric
      peak pressure (TPP) results. Depending on the age, the median tympanometric peak
      pressures were 5 to 10 daPa higher in otologically normal children than in the
      unselected population. The median TPP was -10 daPa in a group of unselected
      children, and -5 daPa in a group of otologically normal children. The
      distribution of ipsi- and contralateral acoustic reflex thresholds is presented.
      Thresholds were higher in younger than in older children. CONCLUSIONS: The
      obtained results give new information on immittance findings in an unselected
      sample of school-aged children who were representative of children in the general
      population. Furthermore, the results are useful as normative immittance values in
      7-, 10-, and 14-yr-old children when the limitations relating to the equipment
      are taken into account.

PMID- 8741965
TI  - Longitudinal study of FM system use in nonacademic settings: effects on language
      development.
AB  - OBJECTIVE: The overall objective of the present study was to assess the efficacy
      of FM system use in the home setting for a group of preschool children with mild
      to-severe sensorineural hearing loss. Changes in language acquisition were
      monitored and compared with similar measures from a group of children who used
      hearing aids. Secondarily, the perceived benefits and practical problems
      associated with FM system use across a variety of nonacademic situations were
      documented. DESIGN: Ten children with mild-to-severe sensorineural hearing loss
      participated in a 2-yr longitudinal study investigating the efficacy of FM system
      use in the home setting. The subjects were divided into two groups: one group was
      instructed to use FM systems at home as often as possible while the other used
      only their personal hearing aids. Changes in language acquisition were monitored
      in both groups. Subjective benefit and the practical problems associated with use
      of FM systems outside of traditional academic environments were monitored via
      daily use logs, a weekly observation inventory, and a situational listening
      profile. RESULTS: The majority of children in both groups improved in all
      measures of language development over the study interval. Although there were
      relatively large individual differences in performance for some measures, no
      statistically significant differences between the FM and hearing aid users were
      found. However, some children in the FM group made unusually large gains in some
      aspects of language development over the study interval. In addition, both
      parents and children reported benefits of FM system use in specific listening
      situations. Throughout the 2-yr study, a number of practical problems associated
      with FM system use outside the classroom were identified. CONCLUSIONS: Formal
      language measures did not yield significant differences between the FM and HA
      groups, but some subjects had rates of language acquisition which suggested that
      FM system use may be beneficial in selected cases. In addition, subjective
      reports of FM system benefit suggest that appropriate use of the device may
      facilitate effective communication in a variety of listening situations. Although
      recent advances in FM system design may minimize some of the factors that
      reportedly restricted consistent FM use in this study, the complexities
      associated with the modes of operation and problems with FM interference remain
      issues that require consistent audiologic monitoring of FM system use in
      nonacademic environments.

PMID- 8741966
TI  - Transient evoked otoacoustic emissions: feasibility in the nursery.
AB  - OBJECTIVE: To assess the feasibility of obtaining transient-evoked otoacoustic
      emissions (TEOAEs) directly in the nursery, to examine the nature of failures in
      this population, and to determine the time requirements for this test relative to
      the auditory brain stem response (ABR). DESIGN: TEOAEs and ABRs were recorded
      from 149 ears, at bedside, in the recovery or intensive care nursery. Subjects
      were selected according to the risk criteria developed by the Joint Committee on
      Infant Hearing (1991). Parametric and nonparametric statistical procedures were
      conducted to describe demographics and test results, to evaluate TEOAE measures
      by subgroups, and to compare infants by pass/fail outcome. Multivariate
      techniques were applied to the data to test implicit hypotheses regarding the
      source of TEOAE failures. In addition, the time required to carry out each test
      was evaluated in an analysis of variance design. RESULTS: 63.5% of the ears
      studied passed both procedures, 5% failed both, and 31.5% passed the ABR but
      failed the TEOAE. Although infants who failed the TEOAE had lower birthweights,
      shorter gestational periods, and were younger at the time of testing, no
      statistical differences were found for nursery (intensive care nursery/recovery),
      bed type (isolette/open crib), ear (left/right), or gender. Infants < 38 wk
      postconceptional age had smaller TEOAE responses and lower noise levels than did
      those > 37 wk. There were no differences in environmental noise levels (at the
      microphone) for passed or failed ears or whether infants were in isolettes or
      open cribs. Statistically prolonged ABR wave I latencies (Z-scores) at 60 and 30
      dB among infants who passed the ABR but failed the TEOAE indicated some
      obstruction to the acoustic stimulus, whereas TEOAE noise measures neither
      distinguished these groups nor identified this condition. Three summary times
      involved in the performance of these tests were obtained: (a) actual test time,
      measured from start to completion of data collection with a stopwatch; (b) total
      test time, defined by the actual test time plus the respective preparation,
      setup, and cleanup (ABR) time; and (c) time reported by the computer system
      during intrinsic sampling. There were no significant differences in actual or
      total test times, but these values were distinguished from the machine time,
      which represented an underestimate of the time required to effectively conduct
      each test. CONCLUSIONS: These findings show that TEOAEs can be acquired in the
      nursery, but the high false-positive rate suggests that alternative or additional
      screening methods, for example, the ABR, must also be available. It must be
      recognized that TEOAE failures increase test time, thereby negating any savings
      relative to ABR screening alone.

PMID- 8741967
TI  - Effects of intratympanically delivered lidocaine on the auditory system in
      humans.
AB  - Since lidocaine is used to relieve the symptoms of Meniere's disease and
      tinnitus, its effects on the human cochlea is of specific interest. In
      experimental animals, topically administered lidocaine affects cochlear
      electrophysiology in a specific, dose-dependent manner. In the current study,
      lidocaine (40 mg in 1 ml of saline) was delivered intratympanically in six
      patients with essentially normal hearing in an attempt to alleviate tinnitus.
      Auditory function was assessed by pure tone audiometry, auditory evoked brain
      stem responses (ABR), and transiently evoked otoacoustic emissions (TEOAE) to
      observe possible drug effect in the auditory system. In five patients, saline was
      injected prior to lidocaine for control purposes. Saline injection did not create
      significant changes in any of the measures. After a 2 hr follow-up period,
      intratympanic injection of lidocaine caused a 2 to 10 dB reduction in TEOAE level
      at 1 to 3 kHz frequencies. This reduction was at its maximum at the 30 min post
      injection sampling point, and was followed by a slow recovery. At 2 hr post
      injection, TEOAE amplitude was still 2 to 4 dB below baseline level. Pure tone
      thresholds were slightly affected 30 min after intratympanic lidocaine injection,
      but were fully recovered 1 hr after the injection. Lidocaine injection did not
      cause any changes in ABR latencies or amplitudes in any of the patients. These
      results suggest that the dose of intratympanically administered lidocaine used
      here has a specific effect on the organ of Corti structures in human subjects,
      without significantly affecting the auditory nerve or central auditory pathways.
      The relationship of the drug effect in conjunction with a possible effect on
      inner ear disorder might help to localize the site of disorder.

PMID- 8741968
TI  - Age of suspicion, identification, and intervention for infants and young children
      with hearing loss: a national study.
AB  - OBJECTIVE: This study was designed to seek a nationwide perspective on the status
      of identification and intervention for infants and young children with hearing
      loss. DESIGN: Three hundred thirty-one parents, whose children ranged from
      infancy to 5 yr of age, returned a mail survey that included respondents from 35
      states. Parents were asked to report the approximate age of suspicion, diagnosis,
      hearing aid fitting, and initiation of early intervention services. Demographic
      information, risk factors, if known, and reasons for delay were also
      investigated. RESULTS: Results revealed substantial delays between parental
      suspicion, audiologic-medical diagnosis, fitting of acoustic amplification, and
      initiation of early intervention services; however, the pattern of delay was
      different for children with known risk factors than it was for those without
      known risk factors. The median age of identification and intervention was lower
      than that reported by some previous investigators, although a considerable range
      was reported for each category. CONCLUSIONS: The median age of identification and
      intervention, although still higher than optimal, may be improving. Further
      research is needed to identify the many factors that continue to delay the timely
      management of hearing loss in young children.

PMID- 8741969
TI  - The effect of low level acoustic stimulation on susceptibility to noise in blue-
      and brown-eyed young human subjects.
AB  - OBJECTIVE: The aim of this study was to investigate the influence of pigmentation
      on the reduction in temporary noise-induced threshold shift (TTS) due to low
      level acoustic stimulation (LLAS). A pigmentation-dependent LLAS effect on TTS
      could be interpreted as a strial melanocyte involvement in LLAS. It could not be
      explained by cochlear sensorineural structure changes only. DESIGN: Teenagers
      were classified according to eye color (n = 6 + 6) and exposed to music at 70 dBA
      6 h per day for 9 days (LLAS). TTS was measured before, during, and after the
      LLAS period. RESULTS: It was shown that LLAS reduced TTS significantly more in
      blue-eyed than in brown-eyed subjects. The difference in TTS remained for at
      least 1 wk after the cessation of LLAS. CONCLUSIONS: It is suggested that the
      observed difference in LLAS effect is due to strial melanocyte differences in
      free radical defense. It is also possible that other cochlear antioxidant enzyme
      systems, responsible for inactivation of harmful oxygen radicals and
      simultaneously involved in melanin synthesis such as the thioredoxin
      reductase/thioredoxin electron transfer system are activated.

PMID- 8741970
TI  - A new concept for Cochlear implant speech processing.
AB  - OBJECTIVE: A new speech processing concept and its implementation cochlear
      implant neural net, simulation and stimulation (CINSTIM), for cochlear implant
      systems is currently under investigation. The main objectives of this new
      strategy are to improve speech perception within the early rehabilitation period
      for prelingually deaf cochlear implant users and to improve speech perception in
      noise for all implant users. The advantage of this approach is the capability to
      assess and compare entirely different speech processing methods within the
      existing implant hardware. DESIGN: The processing concept is based on discrete
      sequences of distinguishable stimulus patterns, robust speech processing, and a
      classifier. The embedded Kohonen classifier employs unsupervised neural net
      algorithms. RESULTS: Initial experimental results have validated the general
      processing scheme as well as the development of this complex software. In
      addition, a limited alphabet of distinguishable stimulus patterns was achieved
      and assessed with experienced users of a conventional cochlear implant system.
      Test subjects were able to learn and recognize up to 60% of these artificial
      patterns after a few training sessions. Currently this speech processing strategy
      is being evaluated through the Cochlear MSP system; however, it is compatible
      with the other computer driven digital cochlear implant systems.

PMID- 8741971
TI  - Complete and restricted alternating treatments designs.

PMID- 8741972
TI  - ISO working group seeks information on high-frequency thresholds.

PMID- 8741973
TI  - Clinical and experimental research. Future directions in neurolinguistics in
      general and brain and language in particular.

PMID- 8741974
TI  - Cognitive approaches to recovery and rehabilitation in aphasia.

PMID- 8741975
TI  - Connectionist modeling of the recovery of language functions following brain
      damage.
AB  - This paper reviews the contribution of connectionism to our understanding of
      behavioral changes in language functions after brain damage. Connectionism is
      founded upon a neural metaphor in that connectionist networks are made up of many
      simple, neuron-like units. It is possible to lesion these networks and explore
      the effects of that damage. It is widely held that damaging connectionist
      networks informs our understanding of neuropsychology and cognitive psychology.
      To what extent then does it currently tell us, or is likely to tell us, anything
      about behavioral change following brain damage? Current connectionist models
      simulate either spontaneous recovery or the effects of retraining, and I discuss
      both approaches. Which is taken at present partly depends upon the connectionist
      framework used as the starting point. Most simulation work involving back
      propagation has focused upon retraining lesioned networks, while work involving
      interactive activation has focused upon making inferences about the time course
      of spontaneous recovery. I discuss research in modeling deep dyslexia, aphasia,
      and dementia. I argue that further research on modeling spontaneous recovery is
      limited by the fixed architecture of most current connectionist networks.

PMID- 8741976
TI  - Relearning after damage in connectionist networks: toward a theory of
      rehabilitation.
AB  - Connectionist modeling offers a useful computational framework for exploring the
      nature of normal and impaired cognitive processes. The current work extends the
      relevance of connectionist modeling in neuropsychology to address issues in
      cognitive rehabilitation: the degree and speed of recovery through retraining,
      the extent to which improvement on treated items generalizes to untreated items,
      and how treated items are selected to maximize this generalization. A network
      previously used to model impairments in mapping orthography to semantics is
      retrained after damage. The degree of relearning and generalization varies
      considerably for different lesion locations, and has interesting implications for
      understanding the nature and variability of recovery in patients. In a second
      simulation, retraining on words whose semantics are atypical of their category
      yields more generalization than retraining on more typical words, suggesting a
      counterintuitive strategy for selecting items in patient therapy to maximize
      recovery. In a final simulation, changes in the pattern of errors produced by the
      network over the course of recovery is used to constrain explanations of the
      nature of recovery of analogous brain-damaged patients. Taken together, the
      findings demonstrate that the nature of relearning in damaged connectionist
      networks can make important contributions to a theory of rehabilitation in
      patients.

PMID- 8741977
TI  - Recovery in deep dysphasia: evidence for a relation between auditory - verbal STM
      capacity and lexical errors in repetition.
AB  - This study investigates the changes in auditory-verbal short-term memory (AVSTM)
      and error patterns in repetition observed in a Wernicke's aphasic, NC, over a
      period of about 2 years following the onset of a left middle cerebral artery
      aneurysm. When first tested, NC demonstrated deep dysphasia, a disorder
      characterized by the production of semantic errors in repetition and a severe
      disability in repeating nonwords. At this stage, his AVSTM span, assessed in a
      pointing task, was less than one item. As NC recovered somewhat, his performance
      on AVSTM tasks improved (span increased to two items), and his pattern of error
      in word repetition changed (fewer semantic errors, more formal paraphasias and
      neologisms). Other features of his span performance after some recovery resembled
      patterns associated with STM-based repetition impairments (reduced recency
      effects and reduced word length effects). In a series of computer simulation and
      empirical studies, we show that NC's repetition performance can be accounted for
      by varying two parameters of an interactive activation model of repetition
      adapted from Dell and O'Seaghdha's (1991) model of production: decay rate and
      temporal interval. These results provide support for the view that AVSTM
      performance depends on storage capacities intrinsic to the language processing
      system. Such a model allows deep dysphasia and STM-based repetition disorders to
      be seen as quantitative variants of the same underlying disturbance.

PMID- 8741978
TI  - Recovery from deep alexia to phonological alexia: points on a continuum.
AB  - Reports of five patients whose deep alexic reading all evolved into phonological
      alexia in a similar fashion point to the hypothesis that deep alexia and
      phonological alexia represent different points on the same continuum. This
      hypothesis is explored further through an examination of previously published
      case reports of eleven patients with phonological alexia. Data from these
      patients suggest that there is a predictable succession of symptoms which form a
      continuum of severity of phonological alexia, with deep alexia as its endpoint.
      An account of the recovery from deep to phonological alexia, based upon a lexical
      (no-rules) model of reading, is provided (Glosser & Friedman, 1990), and the
      implications for therapy are considered. The significance of the notion of a
      continuum of phonological/deep alexia is discussed.

PMID- 8741979
TI  - Differential recovery from impairment to the phonological lexicon.
AB  - Word production was examined in four aphasics diagnosed acutely with neologistic
      jargon and who displayed impairment to the lexical stage of phonological
      production (Kohn & Smith, 1993, 1994a). To investigate the major source of their
      nonword errors (i.e., neologisms, phonemic paraphasias), single word production
      was tested at three different times over the first 6 months postonset, with one
      subject receiving additional testing at 14 months postonset. Two subjects showed
      signs of recovery to the phonological output system with respect to: (1) improved
      word production scores, (2) increased frequency of phonemic paraphasias versus
      neologisms, and (3) increased production of target phonemes. These subjects also
      displayed above-chance production of target phonemes and no significant tendency
      to perseverate phonemes across picture-naming trials. It was argued that this
      pattern reflects a resolving disturbance in retrieving entries from the
      phonological lexicon. The other two subjects showed no improvement in word
      production. They also consistently produced target phonemes at chance levels and
      had a tendency to perseverate phonemes across picture-naming trials. This static
      pattern of performance was considered to reflect loss of information from the
      phonological lexicon. The neuroanatomical damage sustained by each case was
      consistent with these two recovery patterns.

PMID- 8741980
TI  - The treatment of anomia resulting from output lexical damage: analysis of two
      cases.
AB  - This study describes a treatment project, carried out with two anomic subjects,
      RBO and GMA failed to name pictures correctly as a consequence of damage to
      phonological lexical forms; their ability to process word meaning was unimpaired.
      Words that were consistently comprehended correctly, but produced incorrectly by
      each subject, were identified. Some words were treated, whereas some served as
      the control set. A significant improvement was observed in both subjects. As
      predicted by the model of lexical-semantic processing used as the theoretical
      background for the study, improvement was restricted to treated items and did not
      generalize to untreated words, not even to words that were semantically related
      to those administered during treatment. Improvement was long-lasting, as shown by
      the fact that 17 months post-therapy GMA's performance on treated words was still
      significantly better than before treatment. These results are discussed in
      relation to the claim that cognitive models can be profitably used in the
      treatment of language disorders.

PMID- 8741981
TI  - Training wh-question production in agrammatic aphasia: analysis of argument and
      adjunct movement.
AB  - The present research utilized aspects of the Principles and Parameters Approach
      (P&PA; Chomsky, 1991, 1993) in linguistic theory as well as findings from the
      psycholinguistic literature as a basis for examining sentence production in
      aphasic individuals. We examined the production of particular wh-movement
      constructions--wh-questions requiring movement of an argument noun phrase (i.e.,
      who and what questions) and those which require adjunct movement (i.e., when and
      where questions). Using a single-subject experimental treatment paradigm,
      subjects were sequentially trained to produce these wh-questions and, throughout
      training, generalization to untrained wh-questions relying on similar wh-movement
      processes was tested. As well, the influence of training on aspects of narrative
      and conversational discourse was examined. Seven agrammatic aphasic subjects who
      evinced difficulty producing (and comprehending) "complex" sentences (e.g.,
      passives, object relative clauses, wh-questions)--sentences that involve movement
      of noun phrases (NPs) out of their canonical positions, leaving behind a "trace"
      of that movement or "gap"--participated in the study. Subjects were trained to
      produce wh-questions by taking them through a series of steps emphasizing the
      lexical and syntactic properties (e.g., thematic role assignment, movement
      processes, and proper selection of wh-morpheme) of declarative sentence
      counterparts of target sentences. Results revealed improved sentence production
      abilities in all subjects under study in both constrained sentence production
      and, importantly, in discourse tasks. The argument/adjunct distinction was
      observed in the sentence production recovery patterns noted in six of the seven
      subjects. Three of the subjects evinced correct argument movement across trained
      and untrained question structures when wh-questions relying on argument movement
      were trained; similarly, for these subjects, training structures relying of
      adjunct movement resulted in improved adjunct movement. Three of the remaining
      four subjects who required additional treatment to alleviate their wh-morpheme
      selection deficits, too showed covariance between argument and adjunct movement
      structures with each type of movement emerging across structures in temporal
      sequence. We discuss these data in terms of the operations necessary to produce
      wh-questions, the importance of considering linguistic and psycholinguistic data
      when designing treatment programs for language disordered patients, and the
      contribution that detailed recovery data can make both to understanding the
      nature of sentence production deficits and to issues regarding normal sentence
      production.

PMID- 8741982
TI  - Remediation of sentence processing deficits in aphasia using a computer-based
      microworld.
AB  - Byng (1988) has argued that some aphasic patients who show problems in sentence
      comprehension are unable to "map" a syntactic analysis of the sentence form onto
      the thematic roles specified by the verb or preposition in the sentence. In
      Byng's study, therapy aimed at improving the mapping process as applied to
      sentences containing locative prepositions led to improvements not only in the
      comprehension of such sentences but also in the comprehension of reversible verb
      sentences. In the present study, 14 aphasic patients were selected for having
      problems with sentence-picture matching involving reversible verb and preposition
      sentences. These problems were shown to be stable across three pre-intervention
      assessments. All assessments were computer-based and involved the matching of
      written sentences to pictures. A small vocabulary was used in assessment and
      therapy which involved a "microworld" of three characters (ball, box, and star)
      which could engage in a limited number of actions and could occupy a limited set
      of spatial relationships. Before therapy began, all the patients were given an
      assessment battery which included a 40-item Verb Test and a 40-item Preposition
      Test. The patients were then divided into two groups, A and B. Group A received
      two 1-hr sessions of therapy per week for 3 weeks aimed at improving the
      comprehension of verb sentences, then a second full assessment, followed by the
      same amount of therapy aimed at improving the comprehension of preposition
      sentences, and finally a third assessment. Group B received the preposition
      therapy first, followed by the verb therapy. The therapy involved the patient and
      therapist interacting with the computer, either assembling pictures to match
      written sentences ("picture-building mode") or assembling sentences to match
      pictures ("sentence-building mode"). Group A showed a classical "cross-over"
      treatment outcome. Performance on treated verb sentences improved during verb
      therapy and was retained when therapy switched to preposition sentences.
      Performance on treated preposition sentences was unaffected by verb therapy but
      improved when therapy switched to the processing of prepositions. Performance on
      untreated verb and preposition sentences showed a similar pattern, though the
      improvements observed were not as great. Improvement was also shown on a paper
      based "Real World Test" which involved a wider range of more naturalistic
      sentences. Performance on a third aspect of sentence comprehension which the
      patients also had difficulty with, namely the comprehension of morphology,
      remained unchanged throughout, providing further evidence that the effects
      obtained were treatment-specific. The results of Group B were less clear cut.
      Comprehension of both verb and preposition sentences improved during the period
      that prepositions were being treated then remained static during verb treatment.
      Comprehension of morphology remained unchanged throughout. At the level of the
      individual patient, the majority of patients obtained higher scores on both the
      Verb Test and the Preposition Test after therapy, but only three patients showed
      improvements on both verbs and prepositions that were statistically significant.
      Six patients showed significant improvements on verbs but not prepositions while
      one showed the opposite pattern. Only three patients failed to show so much as a
      borderline improvement on either verbs or prepositions. Finally, seven of the
      patients returned for an additional assessment 5 months after completing the
      therapy. These patients, who had demonstrated significant improvements during the
      therapy, were shown to have maintained their improved comprehension skills.

PMID- 8741983
TI  - Assessing the elements contributing to a "mapping" deficit: a targeted treatment
      study.
AB  - Aphasic patients with excellent comprehension of word meanings frequently fail to
      understand simple declarative sentences in which either of two nouns could
      reasonably serve as agent of a transitive action. This study employed targeted
      treatment of this comprehension problem in a chronic aphasic patient (E.A.) in an
      attempt to isolate the source or sources of his comprehension failure. Treatment
      exercises that relied on error feedback in sentence-picture matching or
      verification initially were not effective. Comprehension of active and passive
      sentences improved only after both structures were explicitly compared and linked
      to a picture. Subsequently E.A. maintained consistently accurate interpretation
      of both sentence types in the treatment exercises as long as the full sentence
      was available to him. E.A. learned to assign thematic roles using a limited set
      of cues in the surface structure. Although improvement was reported in untreated
      sentences, the degree of generalization and the level of performance differed
      across tasks and appeared to be attributable to cognitive impairments that were
      not addressed by the treatment. Results are interpreted as evidence suggesting
      that multiple impairments contribute to failure of sentence comprehension tasks.

PMID- 8741984
TI  - Block polycationic oligonucleotide derivative: synthesis and inhibition of herpes
      virus reproduction.
AB  - The block polycationic oligonucleotide (oligo) consisting of a phosphodiester 12
      mer linked to the polycation chain at the 3'-end and cholesteryl group at the 5'
      end was synthesized. The polycation chain was grown on the solid support using
      the monomer, H-phosphonate of 1-O-(4,4'-dimethoxytrityl)-1,3-butanediol. Amino
      groups were introduced in the polymer backbone using 1,4-diaminobutane, and then
      the oligo chain was formed at the free end of the polymer. The last stage of the
      synthesis was the attachment of the cholesteryl group to the 5'-end of the oligo
      prior to cleavage and deprotection of the copolymer. The nucleotide sequence of
      this copolymer, CGTTCCTCCTGC, was complementary to the splicing site of immediate
      early (IE) mRNA 4 and 5 of herpes simplex virus type 1 (HSV-1). The stability of
      the duplexes formed between the copolymer and the complementary 12-mer was
      similar to that of unmodified oligo. The stability of the block polycationic
      oligo against phosphodiesterase digestion was significantly increased compared to
      that of the unmodified oligo. The block polycationic oligo inhibited the
      reproduction of HSV-1 in Vero cells; however, the effect was significantly less
      than the effect of 12-mer oligo modified with cholesterol at the 5'-end. The
      decreased antiviral activity of the copolymer is explained by the polycation
      induced stimulation of the virus infection.

PMID- 8741985
TI  - Boronated epidermal growth factor as a potential targeting agent for boron
      neutron capture therapy of brain tumors.
AB  - In order for boron neutron capture therapy (BNCT) to be successful, a large
      number (approximately 10(9)) of 10B atoms must be delivered to each cancer cell
      in order to sustain a lethal 10B(n, alpha)7Li reaction. The majority of high
      grade gliomas express an amplified epidermal growth factor receptor (EGFR) gene,
      and increased numbers of EGFR are found on the cell surface. If a sufficiently
      large number of 10B atoms could be attached to EGF, the resulting bioconjugates
      might be useful for targeting brain tumors. In order to accomplish this, we have
      boronated a fourth-generation starburst dendrimer (SD) using an isocyanato
      polyhedral borane, Na(CH3)3NB10H8NCO. For conjugation, reactive thiol groups were
      introduced into the boronated SD using N-succinimidyl 3-(2
      pyridyldithio)propionate (SPDP), and EGF was derivatized with m-maleimidobenzoyl
      N-hydroxysulfosuccinimide ester (sMBS). Subsequent reaction of thiol groups of
      derivatized BSD with maleimide groups of derivatized EGF produced stable BSD-EGF
      bioconjugates containing approximately 960 atoms of boron per molecule of EGF. As
      determined by electron spectroscopic imaging, the BSD-EGF initially was bound to
      the cell surface membrane and then was endocytosed, which resulted in
      accumulation of boron in lysosomes. The favorable in vitro properties of these
      bioconjugates suggest that they may be useful for the in vivo targeting of EGFR
      positive brain tumors.

PMID- 8741986
TI  - Rapid characterization of chemically-modified proteins by electrospray mass
      spectrometry.
AB  - Electrospray mass spectrometry (ESI-MS) has been used to examine monoclonal
      antibodies (MAbs), antibody fragments (Fab and Fc), modified fragments, and a
      range of other chemically-modified proteins as part of a study aimed at
      establishing ESI-MS as a method for the characterization of
      radioimmunoconjugates. This has been approached from two angles. Firstly, ESI-MS
      of complexes formed between chelators and other small molecules conjugated to hen
      egg white lysozyme (HEL) (14 kDa) demonstrate the considerable advantages of this
      powerful new technique compared with existing methods for the characterization of
      chemically-conjugated proteins. Molecular weights can be determined rapidly to
      within 0.01-0.05% and with good sensitivity (10-50 pmol total), thus providing
      specific structural information and opening the way for ESI-MS to be applied
      widely for the structural characterization of radioimmunoconjugates. Secondly,
      the conditions for ESI-MS of intact antibodies and antibody fragments have been
      examined in detail, and we have shown that the addition of up to 10 biotin
      molecules to the 50 kDa Fab fragment can be easily detected in ESI mass spectra,
      thus demonstrating the potential for the characterization of modified MAb
      fragments and metabolites. Finally, the strengths and limitations of ESI-MS of
      intact antibodies are discussed, and these results indicate that it may only be
      possible to detect average shifts in the mass of intact antibodies following
      modification.

PMID- 8741987
TI  - Studies on the activity of barnase toxins in vitro and in vivo.
AB  - Pseudomonas exotoxin A (PE) is a protein toxin composed of three structural
      domains which are responsible for cell binding (domain Ia, amino acids 1-252),
      translocation into the cytosol (domain II, amino acids 253-364) and ADP
      ribosylation activity (domain III, amino acids 405-613). We have previously
      described (Prior, T. I., FitzGerald, D. J., and Pastan, I. (1992) Biochem. 31,
      3555-3559) a molecule composed of amino acids 1-412 of PE and the extracellular
      ribonuclease of Bacillus amyloliquefaciens, barnase (Bar), and shown that this
      protein (PE1-412-Bar) is toxic to cells due to its ribonuclease activity, which
      had been delivered to the cytosol. We have now used this model to evaluate the
      role played by the carboxyl end of domain II (amino acids 347-364), domain Ib,
      and the amino end of domain III (amino acids 405-412) in the translocation event.
      Toxins completely lacking domain III, termed PE1-380-Bar, or both domains Ib and
      III, termed PE1-364-Bar, were equally cytotoxic to a murine fibroblast cell line
      (L929) as was PE1-412-Bar. Extending the deletion to include part of the E-helix
      and all of the F-helix of domain II (amino acids 347-364) resulted in a toxin
      (PE1-346-Bar) that was 10-fold less toxic. Previously tested on only murine cell
      lines, we demonstrate that barnase toxins are cytotoxic also to a variety of
      human cell lines. Cytotoxicity was assessed by measuring inhibition of DNA
      synthesis. Surprisingly, PE1-380-Bar is not lethal when injected into mice,
      either intraperitoneally or intravenously, at 9 nmol, which is 2200-fold more
      than the amount required for killing by PE (4 pmol). In cell culture these
      barnase-containing toxins are 100-fold less toxic to murine fibroblast cells than
      PE. Barnase toxin has a greater survival time in the blood of mice than PE, with
      a half-life of 102 min. We conclude that domain II is sufficient to transport
      proteins into the cytosol. Further, since domain Ia can be replaced with other
      cell targeting moieties, we propose that barnase-toxins should be evaluated for
      utility in targeted cancer therapy.

PMID- 8741988
TI  - Characterization of single site ricin toxin B chain mutants.
AB  - DNA encoding ricin B chain was modified by site-directed mutagenesis, and eight
      separate mutant RTB cDNAs including four novel mutants were ligated into the
      baculovirus transfer vector, pAcGP67A. Cotransfection of S. frugiperda Sf9 cells
      with BaculoGold DNA was followed by limiting dilution isolation of recombinant
      baculoviruses. Infection of Sf9 cells at a multiplicity of infection of 5 in the
      presence of 25 mM lactose produced 0.05-1 mg/L of soluble, glycosylated 34 kDa
      proteins immunoreactive with monoclonal and polyclonal antibodies to ricin B
      chain. Mutant ricin B chains were partially purified by monoclonal antibody
      immunoaffinity chromatography to 10-50% purity in near milligram quantities. The
      mutant ricin B chains had decreased lectin binding relative to plant ricin B
      chain as measured by binding to immobilized lactose and asialofetuin and cell
      binding immunofluorescence. The mutant ricin B chains reassociated with plant RTA
      similarly to plant RTB, and the recombinant heterodimers had slightly reduced
      cell cytotoxicity relative to ricin.

PMID- 8741989
TI  - Site-specific attachment of functionalized poly(ethylene glycol) to the amino
      terminus of proteins.
AB  - A convenient method for the construction of site-specifically modified
      poly(ethylene glycol)-protein conjugates is described. This method relies on the
      ability to generate a reactive carbonyl group in place of the terminal amino
      group. If the protein has N-terminal serine or threonine, this can be done by
      very mild periodate oxidation and generates a glyoxylyl group. A method less
      restricted by the nature of the N-terminal residue, but which requires somewhat
      harsher conditions, is metal-catalyzed transamination, which gives a keto group.
      The N-terminal-introduced reactive carbonyl group specifically reacts, under mild
      acidic conditions, with an aminooxy-functionalized poly(ethylene glycol) to form
      a stable oxime bond. Using polymers of different size and shape (linear or
      multibranched), various conjugates of IL-8, G-CSF, and IL-1ra were constructed
      and further characterized with respect to their biological activity and
      pharmacokinetic behavior in rats. Unlike most previous methods, this approach
      places a single PEG chain at a defined site on the protein. It should therefore
      be more likely to conserve biological activity when the latter depends on
      interaction with another macromolecule (unlike enzymic activity which often
      survives multiple PEGylation).

PMID- 8741990
TI  - Purification of subunit B of Shiga toxin using a synthetic trisaccharide-based
      affinity matrix.
AB  - The blood group P1 antigenic trisaccharide (3), which is the receptor-binding
      ligand of Shiga-like toxins, is synthesized in a spacer-equipped form (32) from 2
      (trimethylsilyl)ethyl glucoside 5 and the 1-thiogalactoside building blocks 10
      and 22 in a stereocontrolled, stepwise fashion. Covalent attachment of 32 to
      hydrazine group-containing agarose gel by reductive amination provided the P1
      trisaccharide-containing affinity sorbent which was used for preparative scale
      isolation of subunit B of Shiga toxin.

PMID- 8741991
TI  - Synthesis, purification, and tumor cell uptake of 67Ga-deferoxamine--folate, a
      potential radiopharmaceutical for tumor imaging.
AB  - The vitamin folic acid was covalently linked to the chelating agent deferoxamine
      (DF) via an amide bond using a simple carbodiimide coupling reaction. A mixture
      of two isomers, DF--folate(alpha) and DF--folate(gamma), was produced involving
      the alpha- and gamma-carboxyl group of folic acid, respectively. These two
      isomers were separated by anion-exchange chromatography using a NH4HCO3 gradient.
      Competitive binding studies revealed that only the DF-folate(gamma) is recognized
      by the folate receptor on KB cells, interacting with an affinity comparable to
      unconjugated folic acid. The DF--folate conjugates were radiolabeled with the
      gamma-emitting radionuclide 67Ga3+ and tested for uptake by cultured KB cells
      overexpressing the folate receptor. The cellular accumulation of 67Ga-DF
      folate(gamma) tracer exhibited rapid uptake kinetics in cell culture with a t1/2
      of approximately 3 min. The KB cell association of 67Ga-DF--folate(gamma) was
      competitively blocked by free folic acid, indicating that uptake of the 67Ga-DF-
      folate(gamma) was specifically mediated by the folate receptor. Since the folate
      receptor is overexpressed on the surfaces of many neoplastic cells, these results
      suggest that 67Ga-DF--folate(gamma) complex might be useful as a diagnostic agent
      for noninvasive imaging of folate receptor-positing tumors.

PMID- 8741992
TI  - Labeling a hydrazino nicotinamide-modified cyclic IIb/IIIa receptor antagonist
      with 99mTc using aminocarboxylates as coligands.
AB  - A series of 99mTc complexes containing a hydrazinonicotinamide-conjugated cyclic
      IIb/IIIa receptor antagonist, cyclo(D-Val-NMeArg-Gly-Asp-Mamb-(hydrazinonicotinyl
      5- (6-aminocaproic acid))), were synthesized in high yield using tricine or other
      aminocarboxylates as coligands. These 99mTc complexes have the potential to be
      used as thrombus imaging agents. The radiolabeling of the HYNIC-conjugated cyclic
      IIb/IIIa peptide (HYNICtide) was carried out by reaction with pertechnetate in
      the presence of excess tricine and stannous chloride at pH 4-5. The reaction time
      and temperature depend on the amount of the HYNICtide and pertechnetate used for
      the radiolabeling. Very high specific activity (> or = 20,000 mCi/mumol) can be
      achieved for the complex [99mTc(HYNICtide)(tricine)2] without postlabeling
      purification. The complex [99mTc(HYNICtide)(tricine)2] was found by two reversed
      phase HPLC methods to exist as multiple species, some of which interconvert,
      depending on the temperature, reaction time, and pH of the reaction mixture. The
      presence of these multiple species is most likely due to different bonding
      modalities of either the hydrazine moiety of the HYNICtide or the two tricine
      coligands. The complex [99mTc(HYNICtide)(EDDA)] (EDDA = ethylenediamine-N,N'
      diacetic acid) was prepared either by reacting the cyclic IIb/IIIa HYNICtide with
      pertechnetate, excess EDDA, and stannous chloride at pH 4-5 and 75 degrees C for
      30 min or by reacting excess EDDA with [99mTc(HYNICtide)(tricine)2]. The complex
      [99mTc(HYNICtide)(EDDA)] was found to be stable for at least 12 h in the reaction
      mixture. Three major species were detected in the radio-HPLC chromatograms,
      presumably due to the more limited number of possible coordination isomers.
      Similar results were obtained using other polydentate aminocarboxylates (such as
      HEDTA, N-(2-hydroxyethyl)ethylenediaminetriacetic acid) as coligands. It is clear
      that the replacement of tricine by other polydentate aminocarboxylates produces
      99mTc-HYNICtide complexes with higher stability and fewer coordination isomers.

PMID- 8741994
TI  - N epsilon-cyclosuccinyllysine: synthesis and formation from hemisuccinylated
      polylysine and its hapten conjugates with sulfamethoxazole during acid
      hydrolysis.
AB  - The novel amino acid N epsilon-cyclosuccinyllysine (4) forms as a side reaction
      during acid hydrolysis of N epsilon-hemisuccinylated succinylsulfamethoxazole
      polylysine conjugates. The presence of 4 in hydrolysates can be obscured in amino
      acid analysis. Identification of 4 was based on chromatographic and
      electrophoretic comparisons with authentic N epsilon-cyclosuccinyllysine, which
      was synthesized in high yield by acid-catalyzed ring closure, under anhydrous
      conditions, of N epsilon-hemisuccinyl-L-lysine. The latter was prepared by an
      improved route, starting from N-alpha-(tert-butyloxycarbonyl)-L-lysine. The
      amount of 4 formed is influenced by the extent of succinylation and the
      conditions of hydrolysis and has reached 30 mol % of lysine. Both the
      hemisuccinyllysyl and the haptenized succinyllysyl residues participate in
      cyclization. This was confirmed by the synthesis and hydrolytic behavior of
      hemisuccinylated polylysine (n = 16) and N4,N epsilon
      succinyl(sulfamethoxazole)(lysine). Formation of 4 can result in error in the
      estimation of the degree of ligand substitution based on lysine content in
      synthetic hemisuccinylated skin test antigens and peptide immunogens, especially
      when the degree of epitope substitution is low. 4 appears to be sufficiently
      stable for trial as an amino acid surrogate.

PMID- 8741993
TI  - Indium-111 labeling of low density lipoproteins with the DTPA-bis(stearylamide):
      evaluation as a potential radiopharmaceutical for tumor localization.
AB  - In order to use the LDL receptor pathway to target radionuclides to cancer sites
      for imaging and diagnostic purposes, a labeling procedure of LDL with 111In using
      the DTPA-bis(stearylamide) (L) has been developed. This bifunctional ligand is
      intended to be incorporated into the phospholipid monolayer of LDL and to
      specifically chelate the In3+ cation at the surface. The ligand was incorporated
      into LDL in buffered medium with a 65-80% yield. The L-LDL samples are stable
      over a 24 h period when examined by dialysis, allowing their storage before
      indium-111 radiolabeling. In vitro studies of In-L-LDL particles show that indium
      labeling is rapidly achieved (1 h). More than 85% of the indium atoms are bound
      to the chelating functions of the incorporated DTPA derivatives and less than 10%
      to the nonspecific complexation sites of LDL (e.g., protein residues). After
      incubation in human serum, the indium activity recovered in the LDL fraction of
      In-L-LDL samples (95%) is much higher than in In-LDL samples (35%), pointing out
      the strong stabilizing chelating effect of the ligand. Competitive binding
      studies show that In-L-LDL are recognized by LDL receptors of A549 cells like
      native LDL when the In-L/LDL ratio varies from 5 to 30. All these in vitro
      experiments demonstrate that the In-L-LDL conjugates possess properties suitable
      for further work with in vivo experiments.

PMID- 8741996
TI  - Effect of molecular architecture of poly(N-isopropylacrylamide)-trypsin
      conjugates on their solution and enzymatic properties.
AB  - Polymer-enzyme hybrid conjugates modified by a temperature-responsive polymer,
      poly(N-isopropylacrylamide) (PIPAAm), have been synthesized. We have investigated
      the molecular architecture of PIPAAm-enzyme conjugates by preparing two types of
      PIPAAm-trypsin conjugates, wherein PIPAAm chains are attached by either single
      end or multipoint chemistry. A semitelechelic co-oligomer (IDc) was attached to
      trypsin by single-point conjugation (IDc-trypsin). A copolymer (PIDAAc)
      consisting of acrylic acid and IPAAm randomly linked in polymer chains was
      attached to trypsin using multipoint conjugation (PIDAAc-trypsin). Both
      conjugates exhibited reversible temperature-responsive phase separation. The IDc
      trypsin conjugate exhibited phase separation at the same temperature as pure IDc,
      due to the highly mobile free polymer end group which remains sensitive to small
      temperature changes. The PIDAAc-trypsin conjugate precipitated at higher
      temperatures than pure PIDAAc, whose movement was restricted by multiple binding
      points. Enzyme stability in solution was improved after introduction of PIPAAm
      chains, which prevented autolysis attributed to conjugate steric hindrance.
      Stability under repeated temperature cycling was also dependent on the
      architecture of conjugates; the IDc-trypsin conjugate was more stable than the
      PIDAAc-trypsin. As a consequence, single-end conjugation of polymer to enzyme
      provides novel bioconjugate with novel functionality attributed to attached
      polymer while retaining native biological function with high stability.

PMID- 8741995
TI  - Extended length heterobifunctional coupling agents for protein conjugations.
AB  - A series of extended length heterobifunctional coupling agents is described. The
      successive aminocaproic acid homologation of succinimidyl 4-(N
      maleimidomethyl)cyclohexane-1-carboxylate, a known 9-atom long maleimide active
      ester linker, yielded 16-, 23-, and 30-atom long maleimide active ester
      homologues. The performance study of these coupling agents in automated
      microparticle enzyme immunoassays showed that, in the alpha fetoprotein assay, in
      which the linkers were employed in the construction of the alkaline phosphatase
      antibody conjugates, the signal increased 64% when the length of the linker was
      incremented from 9 atoms to 23 atoms and 82% for the 30-atom long linker as
      compared with the 9-atom homologue. Similar improvements were observed in the
      performance of carbohydrate antigen, marker of ovarian cancer (CA-125),
      immunoassay where the linkers were used for conjugation of the capture antibody
      anti-CA-125 to the microparticle. Thus, a 300% signal improvement resulted when a
      30-atom linker was used instead of the 9-atom homologue. The observed differences
      in the performance of the conjugates are interpreted as resulting from improved
      antibody binding and lowering of the steric hindrance of the complementarity
      determined region of the antibody when longer coupling agents were used.

PMID- 8741997
TI  - No-carrier-added (4-fluoro-3-[131I]iodobenzyl)guanidine and (3-[211At]astato-4
      fluorobenzyl)guanidine.
AB  - With 3-bromo-4-fluorotoluene as starting material, [4-fluoro-3
      (trimethylsilyl)benzyl]guanidine was prepared in five steps in 1.5% overall
      yield. Radioiodination of this silicon precursor using N-chlorosuccinimide in
      trifluoroacetic acid at room temperature for 5 min gave (4-fluoro-3-[131I]
      iodobenzyl)guanidine ([131I]FIBG) in 50-60% radiochemical yield. A byproduct
      which had a retention time in two HPLC systems similar to that of (m
      iodobenzyl)guanidine (MIBG) was formed in about 30% yield. [131I]FIBG was stable
      up to 3 h under these conditions of iodination, indicating that the byproduct is
      not generated as a result of [131I]FIBG degradation. Using hydrogen peroxide as
      the oxidant in aqueous medium and a reaction time of 30 min at 50 degrees C,
      yields of [131I]FIBG could be increased to 75-80%, with less than 7% of the
      byproduct formed under these conditions. Astatination of the silicon precursor
      using N-chlorosuccinimide in trifluoroacetic acid at 70 degrees C gave 65-70%
      radiochemical yield of (3-[211At]astato-4-fluorobenzyl)guanidine ([211At]AFBG) in
      10-15 min; about 17% of the byproduct formation was seen. Astatination of the
      silicon precursor under aqueous conditions using hydrogen peroxide was not
      successful.

PMID- 8741999
TI  - Synthesis and purification of thermally sensitive oligomer-enzyme conjugates of
      poly(N-isopropylacrylamide)-trypsin.
AB  - Using chain-transfer polymerization, we have synthesized oligomers of poly(N
      isopropylacrylamide) [poly(NIPAAm)] with one carboxyl group at the end of each
      oligomer chain. The lower critical solution temperature (LCST) of the oligomers
      is very close to that of homo-poly(NIPAAm) lacking the end carboxyl group. The
      carboxyl groups were activated in methylene chloride using N,N'-dicyclohexyl
      carbodiimide (DCC) and N-hydroxysuccinimide (NHS). A conjugate of trypsin with
      the preactivated oligomer has been prepared. We studied the effect of oligomer to
      enzyme (O/E) ratio in the feed on the O/E ratio of the conjugate (the average
      number of oligomer chains conjugated to one trypsin molecule), assuming that only
      the primary amino groups of lysine residues and the amino terminal of trypsin
      would react. The O/E ratio of the conjugate was estimated by determination of the
      remaining primary amine groups on the trypsin molecule. More than 95% of the
      conjugate can be recovered by thermally induced precipitation.

PMID- 8741998
TI  - Probing nucleic acid geometries: oligonucleotides containing 2'-O
      phenethyladenosine at specific sites.
AB  - The synthesis of 2'-O-phenethyladenosine and its incorporation into an
      oligodeoxyribonucleotide and a chimeric oligodeoxy/oligoribonucleotide are
      described. The study was designed to determine the consequences of site-specific
      induction of such a small, flexible hydrophobic ligand into a nucleic acid.
      Through the use of optical (Tm, circular dichroism) spectroscopy and nuclear
      magnetic resonance, it was discovered that this substitution destabilized the
      duplex and that the benzene ring of the phenethyl group lies in the major groove
      of both the DNA analog and the DNA-RNA duplex structure. The plane of the benzene
      ring lies perpendicular to the stacked bases of the oligonucleotide which, in
      other respects, exhibits relatively normal B-type geometry for the
      oligodeoxynucleotide and a modified A-type geometry in the DNA-RNA duplex. This
      finding has implications for the synthesis of oligodeoxynucleotides containing
      major groove binders as ligands.

PMID- 8742000
TI  - On-off switching of enzymatic reaction by recombinant calmodulin on a solid-phase
      matrix.
AB  - A fusion protein consisting of human calmodulin (CaM) and glutathione S
      transferase (GST) was produced by gene fusion. The fusion protein was
      overexpressed in Escherichia coli as a soluble form and purified with one-step
      affinity chromatography using glutathione-Sepharose. The protein had the
      modulating activity of CaM and the binding capability to glutathione of GST.
      Phosphodiesterase, which is a CaM dependent enzyme, was activated by the fusion
      protein, with the Ca2+ level equal to the level equivalent to a native CaM.
      Furthermore, CaM could be immobilized on a solid-phase matrix through the use of
      GST moiety while its modulating activity was retained. Phosphodiesterase activity
      was switched on and off by the immobilized CaM with or without Ca2+, and repeated
      use of CaM was demonstrated.

PMID- 8742001
TI  - A hepatocyte-targeted conjugate capable of delivering biologically active
      colchicine in vitro.
AB  - A derivative of colchicine was synthesized, in a manner that preserved its
      important structural features, and conjugated to an asialoglycoprotein. The
      conjugate was characterized by ultraviolet-visible spectrophotometry and protein
      analysis. An average coupling ratio of 2 mol of colchicine per mole of
      asialoglycoprotein was achieved. The conjugate was stable to incubation in serum
      but was split into its separate components under chemically reducing conditions.
      Incubation with cells in culture revealed that the conjugate had
      antiproliferative activity similar to that of colchicine, but only in
      asialoglycoprotein receptor-containing cells. There was no effect at all on
      asialoglycoprotein receptor (-) cells. Furthermore, the antiproliferative effect
      of the conjugate on receptor (+) cells was blocked by addition of a large molar
      excess of free asialoglycoprotein. Immunofluorescence microscopy revealed
      disruption of microtubules in cell cultures that were pretreated with the
      conjugate. These results indicate that a colchicine conjugate that is taken up
      specifically into cells by asialoglycoprotein receptors and released
      intracellularly in a biologically active form can be prepared.

PMID- 8742002
TI  - Chiral discrimination in the binding of tris(phenanthroline)ruthenium(II) to calf
      thymus DNA: an electrochemical study.
AB  - The binding of delta-, lambda-, and rac-[Ru(phen)3]2+ (phen = 1,10
      phenanthroline) and delta-, lambda-, and rac-[Ru-(bpy)3]2+ (bpy = 2,2'-bipyridyl)
      with calf thymus DNA has been examined by cyclic and differential pulse
      voltammetric techniques to obtain structural insight into the noncovalent binding
      of the enantiomers to DNA. The insignificant shift in RuII/RuIII peak potentials
      on the addition of DNA suggests that both the oxidized and reduced forms bind to
      DNA to the same extent. Interestingly, DNA selectively decreases the peak
      currents of delta-[Ru(phen)3]2+ but not those of the lambda-enantiomer; rac
      [Ru(phen)3]2+ exhibits an intermediate behavior, thus suggesting that the delta
      form exhibits significant selectivity for B-DNA. The binding constants (K2+) and
      binding site sizes (s) have been determined from the decrease in the peak
      currents. The binding constant (K2+) of delta-[Ru(phen)3]2+ is on the order of
      10(4) M-1 which is less than that for proven intercalators. In contrast, the
      electrochemical behavior of all three forms of [Ru(bpy)3]2+ remains almost
      unaffected in the presence of DNA, suggesting that the complexes might reside on
      the hydrophilic coat of the DNA helix.

PMID- 8742003
TI  - An adduct of cis-diamminedichloroplatinum(II) and poly(ethylene glycol)poly(L
      lysine)-succinate: synthesis and cytotoxic properties.
AB  - A noncovalent adduct of the antineoplastic drug cis-diamminedichloroplatinum
      (cDDP) and a biocompatible graft copolymer of poly(L-lysine) and
      methylpoly(ethylene glycol) succinate is described. Upon incubation of cDDP with
      [O-methylpoly(ethylene glycol)-O'-succinyl]-N- epsilon-poly(L-lysine)n-N-epsilon
      succinate, n = 250-270, highly soluble, long circulating adducts were formed
      which contained 4.3% of platinum by weight. Approximately 60% of the polymer
      associated drug was released during dialysis against saline or serum albumin
      containing saline, with a half-time of release of 63 h. The adducts showed a
      pronounced antineoplastic effect in BT-20 human adenocarcinoma cell cultures. In
      cell proliferation assays, the concentration of half-inhibition of [3H]thymidine
      uptake was 0.9 +/- 0.2 microM for the drug-copolymer adduct compared to 0.3 +/-
      0.1 microM for free cDDP. The adduct showed a long blood half-life (ca. 14 h in
      rats) and accumulated in experimental mammary adenocarcinomas at 2.5-3.5%
      injected dose per gram of tissue. A control adduct of cDDP with the backbone
      portion of the copolymer, poly(L-lysine)-N-epsilon-succinate, had a short half
      life in the bloodstream (ca. 30 min) and low accumulation (0.5% injected dose per
      gram) in tumor. A dual therapeutical effect of methylpoly(ethylene
      glycol)succinylpoly(L-lysine)-succinate as a carrier of cDDP is suggested: (1) as
      a carrier for systemic release of the active drug from the macromolecule while it
      circulates in the bloodstream and (2) as a carrier for on-site delivery which
      results from the release of the drug in the tumor as a consequence of
      accumulation of the copolymer in the tumor.

PMID- 8742004
TI  - Dextran modification of a Fab'--beta-lactamase conjugate modulated by variable
      pretreatment of Fab' with amine-blocking reagents.
AB  - The physical and pharmacological properties of proteins can be altered by
      chemical modification with polymers. Preliminary studies showed that attachment
      of oxidized dextran to the bacterial protein, beta-lactamase (beta L) effectively
      reduced in vivo immunogenicity in mice with no loss of enzymatic activity. This
      report describes a general method for differentially dextran modifying the Fab'
      component of a Fab'--beta-lactamase conjugate by the use of amine-blocking
      reagents. Methyl acetimidate (MeAcm) and the N-succinimidyl derivative of
      (methylsulfonyl)ethyl carbonate (NHS-Msc), reagents which can reversibly block
      primary amines, were used in model studies to modulate the level of available
      reactive amines on the F(ab')2 fragments of both the anti-carcinoembryonic
      antigen antibody, ZCE025, and the antitumor-associated glycoprotein-72 antibody,
      CC49. MeAcm had little or no effect on immunoreactivity and was maximally
      effective in modulating dextran attachment, while NHS-Msc was much less
      effective. A comparison of NHS-Msc and MeAcm is described. Treatment of F(ab')2
      with 5-300 mM MeAcm prior to dextran treatment showed a proportional decline in
      the level of dextran attachment as well as intramolecular cross-linking of the
      protein by the dextran polymers (6 kDa or 33-mer). A conjugate of beta L coupled
      to MeAcm-treated ZCE025 Fab' [reduced F(ab')2] was constructed under standard
      conditions using sulfosuccinimidyl N-[(4-carboxycyclohexyl)methyl]maleimide.
      After dextran modification, this conjugate maintained good immunoreactivity and
      enzymatic activity. Biodistribution studies in tumor-bearing nude mice of
      dextranated and nondextranated conjugate showed comparable overall distribution
      profiles except that the clearance of the dextranated conjugate from both blood
      and tumor was delayed about 48-72 h.

PMID- 8742006
TI  - A new therapeutic monoclonal antibody.

PMID- 8742005
TI  - A biotinylated undecylthiophene copolymer bioconjugate for surface
      immobilization: creating an alkaline phosphatase chemiluminescence-based
      biosensor.
AB  - Methodology is described for the creation of a molecular assembly consisting of
      the enzyme alkaline phosphatase immobilized onto a glass surface using a
      biotinylated conjugated copolymer, poly(3-undecylthiophene-co-3
      thiophenecarboxaldehyde) 6-biotinamidohexanohydrazone. The biotinylated polymer
      is attached to the inside walls of a silanized glass capillary via hydrophobic
      interactions, and a streptavidin-conjugated alkaline phosphatase is interfaced
      with the polymer through the classical biotin-streptavidin interaction. Utilizing
      a simple optical setup, we can detect the activity of as little as approximately
      0.1 fmol of alkaline phosphatase with this molecular assembly. The assembly is
      mechanically robust and retains the majority of bound enzyme activity for up to
      30 days. We have utilized this molecular assembly for the detection of
      organophosphorus-based pesticides. Both paraoxon and methyl parathion inhibit the
      enzyme-mediated generation of chemiluminescence signal. We are able to detect
      paraoxon and methyl parathion concentrations down to 500-700 ppb.

PMID- 8742007
TI  - Optimal management of heart failure.

PMID- 8742008
TI  - New OTC drugs and devices: a selected review.

PMID- 8742009
TI  - Compensation in Canada for resolving drug-related problems.

PMID- 8742010
TI  - Pharmaceutical care innovations in Japan.

PMID- 8742011
TI  - Benefits of certification for pharmacy specialists.
AB  - The objective of the study was to measure the tangible and intangible benefits of
      certification by the Board of Pharmaceutical Specialties (BPS). All BPS-certified
      pharmacists (n = .733) were mailed a survey in October 1933. The response rate
      was 65.5% (n = 480). Approximately 8% of respondents reported a promotion, 16%
      reported a bonus, and 10% reported a raise as a direct result of certification.
      Respondents were asked to indicate their level of agreement with statements
      concerning benefits they had experienced as a result of certification. The
      highest level of agreement about perceived benefits had to do with greater self
      worth, improved competence, and greater marketability. The lowest agreement about
      perceived benefits was related to monetary compensation. This article compares
      responses by pharmacists in three specialties and who hold two types of degrees.

PMID- 8742012
TI  - Moving pharmacists toward providing pharmaceutical care.

PMID- 8742013
TI  - 'Concept pharmacy': bringing pharmaceutical care to life.

PMID- 8742014
TI  - Responses of tonically discharging neurons in monkey striatum to visual stimuli
      presented under passive conditions and during task performance.
AB  - To test whether the responsiveness of tonically discharging neurons from monkey
      striatum is dependent on the motor or rewarding features of the conditioned
      stimuli, we studied the responses of these neurons to visual stimuli presented
      under two behavioral conditions: during an operant task in which the stimulus
      triggered a movement to obtain a reward, and in a non-performing state in which
      the stimulus was consistently followed by a reward outside of a task. Most of the
      neurons tested (110/158) responded to the stimuli presented in both conditions,
      while a relatively small number of neurons (35/158) showed selective responses in
      one or other of the conditions. A gradual disappearance of neuronal responses
      occurred in the passive state when presenting a stimulus which was never followed
      by reward. These results provide evidence that tonic striatal neurons may be
      involved in detecting stimuli predicting reward, regardless of the behavioral
      contingency of those stimuli.

PMID- 8742015
TI  - Cyclic-AMP regulation of calcium-dependent K channels in an insect central
      neurone.
AB  - In the cockroach fast coxal depressor motoneurone, either the muscarinic agonist
      McN-A-343 or dibutyryl cAMP (Db-cAMP) induced a reduction in voltage-dependent
      outward current. The response to McN is due to suppression of a calcium-dependent
      potassium current (IK,Ca) produced secondarily to a reduction in voltage
      dependent calcium current (ICa). The response to Db-cAMP was investigated in
      order to establish whether cAMP might mediate the response to McN. ICa was
      suppressed by 3-isobutyl-1-methylxanthine (IBMX) but not by Db-cAMP. The effects
      of IBMX were therefore unlikely to be the result of phosphodiesterase inhibition.
      Since caffeine also suppressed ICa, the observed effect of IBMX is probably due
      to release of Ca2+ from intracellular stores. IK,Ca, evoked by injection of Ca2+,
      was reduced by Db-cAMP or forskolin but not by McN. These results indicate that
      the electrical response to McN in this neurone is not mediated by changes in
      cAMP.

PMID- 8742016
TI  - Phorbol ester enhances phosphorylated tau protein immunoreactivity in neuronal
      cultures.
AB  - One of the hallmarks of Alzheimer's disease (AD) is neurofibrillary degeneration
      which results from the aggregation of phosphorylated tau proteins into paired
      helical filament (PHF) structures. AD2 is a new monoclonal antibody raised
      against PHF tau which detects neurofibrillary tangles in AD brain. In primary
      neuronal cultures, phorbol ester treatment induced a time- and dose-dependent
      increase in AD2 immunoreactivity quantified by laser confocal microscopy and
      immunoblottings. Alkaline phosphatase treatment reversed these immunocytochemical
      changes. These results suggest that the modifications of neuronal metabolism
      induced by phorbol ester including protein kinase C activation produce an
      increase in phosphorylated tau immunoreactivity.

PMID- 8742017
TI  - GABAA receptor currents recorded from Mueller glial cells of the baboon (Papio
      cynocephalus) retina.
AB  - The effect of gamma-aminobutyric acid (GABA) application on acutely isolated, non
      cultivated Muller glial cells from the baboon retina was studied using the whole
      cell voltage-clamp technique. Application of GABA (0.1 mM) generated inward
      currents at a holding potential of -80 mV as well as an increase in current
      noise. The GABA-activated current had a reversal potential of 18.6 mV and was
      therefore supposed to be a Cl- current (ECl = 5 mV). The GABAA receptor agonist
      muscimol (0.1 mM) elicited an inward current and bicucullin (0.5 mM), a blocker
      of the GABAA receptor, diminished the GABA responses in our experiments
      completely. Baclofen (0.1 mM), a GABAB agonist, neither had an effect when
      applied under conditions where the dominant Muller cell K+ currents were
      unblocked, nor when the K+ currents were blocked by application of Ba2+ (1 mM).
      Glycine (0.1 mM) was ineffective as well. From these results we conclude that the
      baboon retinal Muller cells possess GABAA receptors. However, these have recently
      been discovered on skate Muller cells whereas GABAA receptors could not be found
      on Muller cells of guinea pig, pig, mouse, rat and rabbit.

PMID- 8742018
TI  - Inhibitory input to pause neurons from pontine burst neuron area in the cat.
AB  - Extra- and intracellular recordings were made from pontine pause neurons (PNs) in
      the cat. Spontaneous spikes of PNs were suppressed after single shock stimulation
      of excitatory burst neuron (EBN) area immediately rostral to the abducens
      nucleus. The most effective stimulation site for the suppression was the region
      where long-lead burst neurons (LLBNs) were predominantly located. Intracellular
      recordings from PNs showed that stimulation of the LLBN area induced short
      latency inhibitory postsynaptic potentials (IPSPs) in PNs and that steep
      hyperpolarization of PNs associated with quick phases of nystagmus occurred prior
      to an abrupt change in abducens nerve activity. Results suggest that a pause of
      PN spikes associated with quick phases is, at least in part, produced by
      inhibitory action mediated through LLBNs.

PMID- 8742019
TI  - Effects of nitric oxide donors sodium nitroprusside and 3-morpholino-sydnonimine
      on prolactin secretion in conscious rats.
AB  - In the present study, we have examined the possible involvement of the central
      nitric oxide (NO) pathway in the control of prolactin secretion in vivo. The
      effects of intracerebroventricular (i.c.v.) injections of L-arginine (L-Arg), a
      precursor of NO, N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of
      NO synthase (NOS), and of sodium nitroprusside (SNP) and 3-morpholino-sydnonimine
      (SIN-1), NO donors, on basal prolactin levels were studied in conscious male
      rats. Microinjections of L-Arg (100 and 500 mu g) or L-NAME (100 and 500 mu g)
      did not modify plasma prolactin levels, however i.c.v. injections of both SNP (1,
      5, 10 and 20 mu g) and SIN-1 (1, 10 and 100 mu g) induced dose-dependent
      increases in these levels although SNP was much more potent than SIN-1. These
      results suggest a role of NO in the control of prolactin secretion.

PMID- 8742020
TI  - Stimulation by nerve growth factor of neuropeptide synthesis in the adult rat in
      vivo: bilateral response to unilateral intraplantar injections.
AB  - Unilateral intraplantar injections (1/day for 3 days) of 4 mu g nerve growth
      factor (NGF) into the rat hindpaw increased the expression of prepro-tachykinin
      (PPT)- and prepro-calcitonin gene-related peptide (ppCGRP)-mRNA in bilateral L5
      dorsal root ganglia (DRGs). This was accompanied by an increase of CGRP-like
      immunoreactivity in the ipsi- and contralateral sciatic nerve but by no
      detectable change of CGRP-IR in other afferents. NGF injections into the skin of
      one ear or into the plantar side of one forepaw increased CGRP-IR in the
      respective afferents (trigeminal ganglion, or nerves arising from the brachial
      plexus, respectively), but had no effect on sciatic CGRP-IR. This suggests that
      the NGF-induced symmetrical increase of CGRP synthesis in L5 DRGs was not caused
      by systemic action of NGF, which, therefore, may be a useful tool to further
      investigate mechanisms which are responsible for contralateral effects of
      unilateral inflammation.

PMID- 8742021
TI  - Protein kinase inhibitor attenuates apoptotic cell death induced by amyloid beta
      protein in culture of the rat cerebral cortex.
AB  - Amyloid beta protein (A beta) is deposited characteristically in the brain of
      patients with Alzheimer's disease. Effects of protein kinase inhibitors (H-89, H
      7, KN-62) on A beta-induced neuronal cell death were examined in primary culture
      of dissociated cerebral cortical cells. beta(25-35), the active fragment of A
      beta, induced neuronal cell death with apoptotic features including chromatin
      condensation and DNA fragmentation. The cell death was attenuated by
      cycloheximide or by H-89, a specific protein kinase A (PKA) inhibitor, but not by
      H-7 or KN-62. These data suggest that beta(25-35) induces apoptotic cell death
      through the PKA-mediated pathway.

PMID- 8742022
TI  - Biphasic reorganization of somatotopy in the primary motor cortex follows facial
      nerve lesions in adult rats.
AB  - Effects of facial nerve transection were studied on muscle responses evoked by
      electrical stimulation in the primary motor cortex (MI) of adult rats. In intact
      animals, activated muscles varied according to the somatotopic representation
      map, and responses were restricted to the contralateral side. Unilateral
      transection of the facial nerve extinguished contralateral vibrissal responses,
      while ipsilateral vibrissae began to respond within 4 min. This abnormal response
      (primary change) was transient and gradually disappeared within hours to days.
      Instead, contralateral movements of forepaw and eye/eyelid muscles could be
      evoked from increasing portions of the former vibrissal field (secondary change),
      in which many points became unresponsive. After 4 days, the former vibrissal
      field had shrunk to a small central part, where ipsilateral vibrissae
      responsiveness remained. The secondary modification was stable for at least 2
      weeks. Since the primary change is rapid, transient and may be mimicked by
      picrotoxin, it may be based on disinhibition of commissural connections, while
      the secondary change is longlasting and therefore may include some form of
      reorganization of associational synapses.

PMID- 8742023
TI  - Motion sickness during off-vertical axis rotation: prediction by a model of
      sensory interactions and correlation with other forms of motion sickness.
AB  - Motion sickness (MS) susceptibility of 108 normal subjects was measured during
      off-vertical axis rotation (OVAR) as a function of angular velocity (60-180
      degrees/s). The chair rotated about a longitudinal axis tilted 30 degrees with
      respect to gravity. For each velocity, we measured the duration of exposure
      necessary to evoke a moderate malaise, with a limit of 30 min. MS appeared the
      fastest at a rotation velocity of 105 degrees/s; higher or lower velocities were
      less provocative. These results are in good agreement with predictions made by
      Zupan et al. [in ICANN'94, Springer-Verlag, 1995] by means of a MS mathematical
      model derived from a model of sensory interactions [Droulez and Darlot, in
      Attention and Performance, Vol. 13, Lawrence Erlbaum, Hillsdale, 1989]. We also
      found that MS susceptibility during OVAR is positively correlated with
      susceptibility to other forms of MS. Since OVAR induces sensory messages very
      different from those induced by other provocative stimulations, this could
      suggest that the sensitivity of a common final vegetative locus is an important
      factor of the individual differences in susceptibility to MS.

PMID- 8742024
TI  - Depressor pathway involved in somatosympathetic reflex in cats.
AB  - The present study aimed to identify direct vasodepressor pathways from the
      rostral ventrolateral medulla (RVLM) to the spinal cord and their role in
      mediation of somatosympathetic reflexes. Vasopressor and depressor areas were
      identified by stimulating various sites of RVLM electrically and/or chemically in
      anesthetized cats. Electrical lesions on the pressor areas abolished the pressor
      response evoked by peripheral C-fiber activation while the depressor response
      remained. Electrical lesions on the depressor areas decreased the depressor
      response evoked by A delta-fiber stimulation. To characterize the neurons
      involved, 17 medullospinal sympathetic neurons were identified
      electrophysiologically. While most of them were sympathoexcitatory, three
      medullospinal tract cells were found to be sympathoinhibitory neurons. From these
      results we concluded that a minor group of neurons in the RVLM is
      sympathoinhibitory and is involved in mediation of somatosympathetic depressor
      response.

PMID- 8742026
TI  - Differential responses between CA1 pyramidal cells and granule cells to ischemic
      insult in rat hippocampal slices.
AB  - Differential responses between CA1 pyramidal cells (PCs) and granule cells (GCs)
      to transient ischemic insults (oxygen and glucose deprivation, Hypo center dot G(
      )) were studied in rat hippocampal slices using simultaneous recordings of
      membrane potentials and intracellular Ca2+ concentrations ([Ca2+]i). The average
      resting membrane potentials before Hypo center dot G(-) were significantly
      different between PCs (-66.5 +/- 1.5 mV) and GCs (-78.5 +/- 2.0 mV). In PCs, Hypo
      center dot G(-) produced an initial hyperpolarization and a subsequent rapid and
      large depolarization. In contrast, in GCs, Hypo center dot G(-) produced a
      gradual depolarization with an initial slight hyperpolarization. [Ca2+]i
      increased corresponding to the depolarization. The [Ca2+]i levels during Hypo
      center dot G(-) and after reoxygenation were significantly higher in the CA1 than
      in the dentate gyrus. These results suggest that PCs are more susceptible to Hypo
      center dot G(-) than GCs, as judged by the speed of depolarization and the
      elevation in [Ca2+]i.

PMID- 8742025
TI  - Induction of apoptosis in a Drosophila neuronal cell line by calcium ionophore.
AB  - Apoptotic type cell death was induced by the calcium ionophore, A23187, in a
      Drosophila CNS derived cell line, ML-DmBG2-c2. It was judged by the
      ultrastructural observations and internucleosomal DNA fragmentation, typical
      characteristics of apoptosis. The ionophore failed to induce apoptosis in Ca2+-
      free medium, which suggests that the increase of intracellular Ca2+ concentration
      by the treatment of A23187 triggers apoptosis in the clonal cells.

PMID- 8742027
TI  - Impairment of maze learning in rats following long-term glucocorticoid
      treatments.
AB  - The present study examined the influence of long-term glucocorticoid treatment on
      a maze learning task on a radial 8-arm maze in rats. Either 100 mg cholesterol
      (as a control), or corticosterone, bead was implanted in rats for a period of 3
      months, beginning at 12 weeks of age. The effect of this treatment on the maze
      learning task was evaluated during or 4 weeks after the treatments. In both
      experiments, corticosterone-implanted rats showed an increase in number of trials
      to attain at least seven correct choices in the first eight choices in five
      consecutive trials (P < 0.05). We concluded that long-term glucocorticoid
      exposure resulted in an impairment of the hippocampal functions, i.e. learning
      and memory, similar to that found in aged hippocampus.

PMID- 8742028
TI  - M3 muscarinic receptors mediate cholinergic excitation of the spontaneous
      activity of subthalamic neurons in the rat.
AB  - The effect of the muscarinic antagonist on carbachol-induced increase in
      spontaneous activity of neurons of the subthalamic nucleus was examined by
      recording the extracellular unitary activity in an in vitro slice preparation.
      Carbachol produced (98% of the 263 neurons tested) an increase (twofold of the
      basal at 500 nM) of the discharge frequency. The EC50 for the carbachol-induced
      effect was 375 +/- 8.7 nM (mean +/- SEM). The response was blocked by muscarinic
      antagonists in a dose dependent manner. However, the IC50 (94 +/- 3 nM) for the
      M3 antagonist 4-diphenyl acetoxy-N-methyl piperidine methobromide (4-DAMP) was
      considerably less than the other muscarinic antagonists (M1 antagonist
      pirenzepine, IC50 1340 +/- 110 nM; M2 antagonist AF-DX-116, IC50 6780 +/- 690
      nM). These results suggest that the cholinergic input to the rat subthalamic
      nucleus exerts a postsynaptic excitatory action and this effect is likely
      mediated via muscarinic receptor type 3.

PMID- 8742029
TI  - Immunocytochemical localization of adrenomedullin-like immunoreactivity in the
      human hypothalamus and the adrenal gland.
AB  - Adrenomedullin is a potent vasodilator peptide that was isolated from
      pheochromocytoma. Localization of adrenomedullin-like immunoreactivity was
      studied by immunocytochemistry in the human hypothalamus and adrenal gland.
      Adrenomedullin-immunoreactive cell bodies were found in the paraventricular,
      supraoptic and infundibular nuclei of the hypothalamus. Both magnocellular and
      parvocellular cells of the paraventricular nucleus were positively immunostained.
      Adrenomedullin-like immunoreactivity was localized in the adrenal medulla. No
      positive immunostaining was observed in the vascular endothelium, vascular smooth
      muscle cell or adrenal cortex. The preabsorption of the antiserum with synthetic
      human adrenomedullin (1-52) abolished the immunostaining. These findings indicate
      that adrenomedullin-like immunoreactivity is localized in the paraventricular,
      supraoptic and infundibular nuclei as well as in the adrenal medulla, and suggest
      that adrenomedullin acts as a neurotransmitter, a neuromodulator or a
      neurohormone in the human hypothalamus.

PMID- 8742030
TI  - Activation of group I mGluRs potentiates NMDA responses in rat hippocampal
      slices.
AB  - The pharmacology of the metabotropic glutamate receptor (mGluR)-mediated
      potentiation of N-methyl-D-aspartate (NMDA)-evoked depolarisations in the CA1
      region of rat hippocampal slices was investigated using an extracellular grease
      gap method. The group I and II mGluR agonist (1S,3R)-1-aminocyclopentane-1,3
      dicarboxylic acid ((1S,3R)-ACPD; 10 mu M) potentiated responses to NMDA (15-25 mu
      M), giving a dose ratio of 0.84 +/- 0.02. The mGluR group I specific agonist
      (RS3,5-dihydroxyphenylglycine (DHPG) (3-10 mu M) also induced a dose-dependent
      and reversible enhancement of responses to NMDA (dose ratio for 10 mu M DHPG was
      0.77 +/- 0.02). In contrast, the group II selective agonist (2S,1'R,2'R,3'R)-2
      (2',3'-dicarboxycyclopropyl)glycine (DCG-IV; 0.5-1 mu M) and the group III
      specific agonist (S)-2-amino-4-phosphonobutanoate (L-AP4; 50 mu M) caused little
      or no potentiation of responses to NMDA. The potentiation induced by 3-5 mu M
      DHPG was reversibly antagonised by the group I and II antagonist (+)-alpha-methyl
      4-carboxyphenylglycine ((+)-MCPG; 1 mM). The present findings demonstrate that
      activation of group I mGluRs enhance NMDA responses in the hippocampus.

PMID- 8742031
TI  - Loss of nucleus basalis magnocellularis, but not septal, cholinergic neurons
      correlates with passive avoidance impairment in rats treated with 192-saporin.
AB  - Intraventricular injection of 192-saporin, an immunotoxin directed at the low
      affinity neurotrophin receptor (p75NGFr), selectively destroys cholinergic
      neurons in the basal forebrain (CBF). In the present study, we sought to
      determine if there was a correlation between degree of CBF neuron destruction and
      degree of passive avoidance behavioral impairment. 192-saporin caused a decrease
      in the number of p75NGFr + neurons in both nucleus basalis magnocellularis (Nbm)
      and medial septal nucleus/diagonal band of Broca (MS/DBB). All rats had >95% loss
      of the p75NGFr + cholinergic neurons in the MS/DBB, but there was variation in
      the extent of the Nbm cell loss. A significant correlation was found between the
      severity of impairment of passive avoidance learning and the magnitude of the
      loss in the number of p75NGFr + neurons in the Nbm. Step-through latency also
      correlated significantly with the magnitude of loss of AChE histochemical
      staining intensity in dorsolateral neocortex ipsilateral to the injection of 192
      saporin. These data show that >95% loss of cholinergic neurons in MS/DBB is not
      sufficient to impair passive avoidance learning. However, in the presence of
      severe loss of cholinergic neurons from the MS/DBB, the resulting deficit in
      passive avoidance behavior is proportional to the degree of cholinergic neuron
      loss from the Nbm. These results are interpreted as support for the hypothesis
      that the cholinergic projection from Nbm to neocortex plays a role in passive
      avoidance behavior.

PMID- 8742032
TI  - p53 involves cytosine arabinoside-induced apoptosis in cultured cerebellar
      granule neurons.
AB  - The tumor suppressor p53 gene plays a key role in controlling the cell cycle
      checkpoint and in apoptosis following the exposure of normal cells to DNA damage.
      To investigate the role of p53 in cytosine arabinoside (Ara C)-induced cell death
      of CNS neurons, we examined the effect of Ara C on the survival of cultured
      cerebellar granule neurons from normal wild-type and p53 null mutant mice. When
      the neurons from wild-type mice were cultured with Ara C, they gradually died
      after 24 h in culture. In contrast, the neurons from p53 null mutant mice showed
      a resistance to the Ara C neurotoxicity. These results indicate that p53 involves
      Ara C-induced apoptosis in cultured cerebellar granule neurons, in which DNA
      damage may initiate the apoptotic death program of the neurons.

PMID- 8742033
TI  - Characteristic changes in sleep patterns during pregnancy in rats.
AB  - The purpose of this study was to evaluate changes in sleep patterns during
      pregnancy to better understand sleep regulation during pregnancy. We
      uninterruptedly recorded electroencephalogram (EEG), electromyogram (EMG), and
      brain temperature (Tbr) throughout pregnancy in rats. The duration of non-rapid
      eye movement (non-REM) sleep decreased after day 5 of pregnancy associated with
      an inverse increase in the number of non-REM sleep episodes. Thus, the amount of
      total non-REM sleep time remained constant throughout pregnancy. The amount of
      total REM sleep time decreased on day 17 of pregnancy after which the reduced
      state was sustained. That was mainly due to a decrease in the number of REM sleep
      episodes. Brain temperature (Tbr) gradually decreased as pregnancy advanced,
      reaching its lowest value 3 days before delivery. These observations provide a
      better understanding of the sleep patterns during pregnancy, and useful
      information for investigation of mechanisms of sleep regulation during pregnancy.

PMID- 8742034
TI  - SR 57746A attenuates cytostatic drug-induced reduction of neurite outgrowth in co
      cultures of rat dorsal root ganglia and Schwann cells.
AB  - A co-culture system of intact rat dorsal root ganglia (DRG) with Schwann cells
      was used to evaluate the potential neurotrophic activity of SR 57746A.
      Neuritogenesis from DRG was measured with an image analysis system following
      exposure to different concentrations of SR 57746A. Neurite outgrowth of intact
      DRG was increased by SR 57746A and this was more obvious in the presence of co
      cultured Schwann cells. The neuroprotective properties of SR 57746A were studied
      in co-cultures of DRG and Schwann cells, in which neuritogenesis was reduced by
      the cytostatic drugs cisplatin, vincristine and taxol. It was found that neurite
      outgrowth from DRG treated with cisplatin (3 micrograms/ml) and 10 microM SR
      57746A for 3 days was significantly higher than after treatment with cisplatin
      alone. Similarly, neuritogenesis from DRG treated with taxol (0.01 microgram/ml)
      or vincristine (0.5 ng/ml) in combination with 10 microM SR 57746A was
      significantly increased compared to treatment with taxol or vincristine alone.
      When intact DRG were incubated in vitro with 3 micrograms/ml cisplatin and
      without Schwann cells, 10 microM SR 57746A also had a neuroprotective effect.
      These data suggest that SR 57746A has neuroprotective potential and that this
      effect does not depend solely on the presence of Schwann cells.

PMID- 8742035
TI  - Dynorphin neurotoxicity induced nitric oxide synthase expression in ventral horn
      cells of rat spinal cord.
AB  - Nitric oxide (NO) mediation in the spinal cord injury induced by intrathecal
      (i.t.) dynorphin (Dyn) administration was studied with NADPH-diaphorase (Nd)
      histochemistry. Normally, there was rarely NO synthase (NOS) activity in spinal
      cord motomeurons, and Dyn A(1-17) 10 nmol, which produced only transient
      paralysis, did not induce Nd/NOS expression in ventral horn cells. After a
      paralyzing dose of i.t. Dyn A(1-17) 20 nmol, which definitely produced permanent
      paraplegia and neuronal death, Nd/NOS began to express in motoneurons at 30 min,
      increased in numbers and intensities at 2-4 h and persisted up to 8 h. Most of
      Nd/NOS motoneurons disappeared at 24 h coincident with the neuronal death. Quite
      a few intensively-stained Nd-positive small cells and swollen varicosities became
      visible only in rats with permanent paraplegia and neuronal death, beginning at 2
      h, maximizing at 3-4 h and remaining up to 24 h. These results suggest that NOS
      expression was induced in the ventral horn of spinal cord, including small cells
      and varicosities as well as motoneurons closely correlated in time and degree
      with pathological changes in motoneurons caused by spinal Dyn neurotoxicity.

PMID- 8742036
TI  - Interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF) inhibit long-term
      potentiation in the rat dentate gyrus in vitro.
AB  - The effects of the cytokine, interleukin-1 beta (IL-1 beta), and its receptor
      antagonist IL-1ra, were studied on long-term potentiation in the dentate gyrus of
      rat hippocampal slices. Field excitatory postsynaptic potentials were recorded
      extracellularly in the molecular region of the dentate gyrus in response to
      stimulation of the medial perforant path. Low frequency synaptic transmission was
      unaffected by IL-1 beta (1 ng/ml), but pre-treatment with IL-1 beta completely
      blocked induction of long-term potentiation. Co-application of IL-1 beta and IL
      1ra (100 ng/ml) attenuated the inhibitory effect of IL-1 beta. In parallel with
      these findings, we demonstrate that IL-1 beta also inhibited 45Ca influx into the
      slices. The inhibitory effect of IL-1 beta on induction was mimicked by tumour
      necrosis factor (TNF; 4.5 ng/ml) and lipopolysaccharide (LPS; 10 micrograms/ml).
      These results indicate a modulatory role for cytokines in hippocampus and suggest
      that the inhibitory effect of IL-1 beta on long-term potentiation may relate to
      its inhibitory effect on calcium channel activity.

PMID- 8742037
TI  - Sub-chronic cold stress reduces 5-HT1A receptor responsiveness in the old but not
      in the young rat.
AB  - The inhibitory effect of the prototypical 5-hydroxytryptamine (5-HT)1A receptor
      agonist 8-hydroxy-2-(di-n-propyl amino)tetraline (8-OH-DPAT) on forskolin
      stimulated adenylyl cyclase activity, has been examined as an index of the
      functional activity of 5-HT1A receptors in the hippocampus of young (3 months)
      and old (18 months) rats exposed during 24 h or 5 days to cold. In both young and
      old rats exposed to cold stress during 24 h, there was a reduction in the potency
      (EC50) and/or the maximal inhibitory effect (Emax) of 8-OH-DPAT in reducing
      forskolin-induced cAMP accumulation. The properties of the hippocampal 5-HT1A
      sites labelled by [3H]8-OH-DPAT were not affected by these stressful conditions.
      Moreover, while the sensitivity of 5-HT1A receptors to 8-OH-DPAT in young rats
      returned to control values after 5 days of cold exposure, old rats still
      exhibited a significant desensitization of 5-HT1A receptors as compared to naive
      animals. These results point out the capacity of young but not of old rats to
      adapt to the aversive effects of a subchronic stressor.

PMID- 8742038
TI  - Aminooxy-analogues of spermidine: new partial agonists and antagonists at the
      polyamine site of the rat hippocampal NMDA receptor complex.
AB  - The amino-1-oxy- and amino-8-oxy-analogues of spermidine (1-O-SPD and 8-O-SPD)
      were tested in vitro with rat hippocampal membranes as potential modulators of
      the N-methyl-D-aspartate (NMDA) receptor complex via the polyamine regulatory
      site. In the presence of 1 microM glutamate and glycine, the binding of the NMDA
      channel ligand [3H]MK-801 was stimulated by 8-O-SPD (EC50 = 50 microM); 1-O-SPD
      was without significant influence at concentrations up to 1 mM. Addition of 2 and
      4 microM of the polyamine agonist spermine eliminated the stimulatory property of
      8-O-SPD, whereas 1-O-SPD was inhibitory under these conditions (IC50 = 274 and
      481 microM, respectively). At higher concentrations of spermine, both compounds
      were inhibitory. Inhibition of [3H]MK-801 binding by the inverse polyamine
      agonists 1,10-diaminodecane, 1,12-diaminododecane, and arcaine was attenuated by
      1 mM 1-O-SPD. The data are compatible with the notion that 8-O-SPD is a partial
      polyamine agonist and that 1-O-SPD is an antagonist without intrinsic activity.

PMID- 8742039
TI  - Monoaminergic neurotransmitters, their precursors and metabolites in brains of
      Alzheimer patients.
AB  - The catecholamines dopamine (DA), noradrenaline (NA) and adrenaline (A), their
      aminoacid precursors tyrosine (Tyr), L-3,4-dihydroxyphenylalanine (L-DOPA), two
      of their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3
      methoxy phenyl glycol (MHPG), serotonin (5-HT) and its precursor tryptophan
      (Trp), were measured by high pressure liquid chromatography (HPLC) with
      electrochemical detection in seven regions (globus pallidus, putamen, nucleus
      amygdalae, nucleus caudatus, substantia nigra, gyrus cinguli and raphe) of
      postmortem brains from eight histologically verified cases with Alzheimer's
      disease (AD) and six histologically normal controls. Concentrations of L-DOPA,
      DA, DOPAC, NA and 5-HT were significantly reduced, while Tyr and MHPG
      concentrations were significantly increased in AD versus control patients. The
      concentrations of Trp and A in AD patients were not significantly different from
      controls. Furthermore, for most brain regions examined, significant negative
      correlations between Tyr and DA as well as between NA and MHPG levels were found.
      These data confirm and extend findings of monoaminergic systems disturbances in
      AD, emphasize the significance of dopaminergic deficit for AD and suggest that in
      pharmacotherapy of AD, attempts to restore deficits of the transmitter systems
      should be directed to the monoaminergic, in particular the dopaminergic system.

PMID- 8742040
TI  - Exposure of rat hippocampal neurons to amyloid beta peptide (25-35) induces the
      inactivation of phosphatidyl inositol-3 kinase and the activation of tau protein
      kinase I/glycogen synthase kinase-3 beta.
AB  - Exposure of rat hippocampal neurons to the peptide amyloid beta (A beta) (25-35)
      as well as A beta (1-40) peptides enhances phosphorylation of tau to a paired
      helical filament (PHF)-state through activation of tau protein kinase I (TPK
      I)/glycogen synthase kinase-3 beta (GSK-3 beta) [Busciglio, J., Lorenzo, A., Yeh,
      J. and Yankner, B.A., Neuron, 14 (1995) 879-888; Takashima, A., Ishiguro, K.,
      Noguchi, K., Michel, G., Hoshi, M., Sato, K., Takahashi, M., Hoshino, T., Uchida,
      T. and Imahori, K., Neurosci. Meeting Abstr., 671 (1995) 17]. In order to examine
      the effects of A beta treatment on intracellular signaling mechanism, we have
      investigated the role of phosphatidyl inositol-3 (PI-3) kinase in the
      phosphorylation of tau. A beta (25-35) exposure induced an inactivation of PI-3
      kinase and an activation of TPK I/GSK-3 beta in rat hippocampal culture.
      Wortmannin, an inhibitor of PI-3 kinase, also activated TPK I/GSK-3 beta, leading
      to an enhancement of tau phosphorylation and neuronal death in hippocampal
      culture. These results suggest that A beta (25-35) inhibition of PI-3 kinase
      results in the activation of TPK I/GSK-3 beta, the phosphorylation of tau, and
      resultant neuronal death in rat hippocampal neurons.

PMID- 8742041
TI  - Intact female rats are more susceptible to the development of tactile allodynia
      than ovariectomized female rats following partial sciatic nerve ligation (PSNL).
AB  - As previously reported, this laboratory has determined that female rats are more
      prone to develop tactile allodynia, an indicator of neuropathic pain, than male
      rats using the partial sciatic nerve ligation (PSNL) model. In order to further
      characterize this gender difference, the role of ovarian hormones in predisposing
      female rats to the development of tactile allodynia was investigated. In a double
      blind randomized trial, 12 intact and 12 ovariectomized (ovx) female rats
      underwent PSNL of the right rear leg. Sham 1 operated (exposure of the nerve
      without ligation; 2 intact, 2 ovx) and sham 2 operated (incision through skin
      only; 1 intact, 2 ovx) controls were also included in the study groups. Animals
      were evaluated on 3 consecutive days for withdrawal from touch with von Frey
      filaments on post-injury days 13-15, 20-22 and 27-29. A significant difference
      was observed at post-injury days 20-22 and 27-29 between the two groups. The
      intact group resulted in 12/12 animals that were statistically more sensitive
      than sham groups, compared to 6/12 for the ovx group. At post-injury days 13-15
      no statistical difference was seen between the two groups (8/12 for intact versus
      10/12 for ovx). This study indicates that ovarian hormones, via some unknown
      mechanism, predispose female rats to develop tactile allodynia following injury.

PMID- 8742042
TI  - Parapyramidal rostroventromedial medulla as a respiratory rhythm modulator.
AB  - After inhalation of 15% CO2, immunoreactions to glutamate and glutamic acid
      decarboxylase were found in some c-Fos or c-Jun-labeled neurons distributed in
      the reticular region just dorsal to the pyramidal tract in the rostroventromedial
      medulla (parapyramidal RVMM). This region forms vertically the narrow strip
      between the nucleus raphe pallidus and nucleus parapyramidalis superficialis, and
      extends rostrocaudally from the level just ahead of the inferior olivary complex
      to the level just behind the nucleus of the trapezoid body. When we placed
      lesions with kainate in the parapyramidal RVMM, hyperpneic and tachypneic
      responses to brief inhalation of 15% CO2 were completely abolished, and the
      eupneic rhythm changed into the gasping rhythm. This study suggests that the
      parapyramidal RVMM consists of neuronal substrates that subserve as the
      respiratory rhythm modulator.

PMID- 8742043
TI  - Nitrergic neurons in the canine intrinsic laryngeal muscle.
AB  - Nitrergic ganglionic cells located in the canine intrinsic laryngeal muscle were
      studied by NADPH-diaphorase (NADPH-d) histochemistry and neuronal nitric oxide
      synthase (nNOS) immunohistochemistry. Cells intensely stained by NADPH-d
      histochemistry were found between the striated muscle fibers of the intrinsic
      laryngeal muscle. Most of these cells were bipolar or pseudounipolar in form.
      Some NADPH-d negative cells were observed to be enveloped in a mesh by varicose
      NADPH-d positive nerve fibers. The findings obtained by nNOS immunohistochemistry
      corresponded well with those obtained by NADPH-d histochemistry, indicating that
      NADPH-d activity in the ganglion in the intrinsic laryngeal muscle is nNOS. The
      present findings clearly indicate that some of the ganglion cells located in the
      canine intrinsic laryngeal muscle are nitrergic, and that the ganglionic cells
      synapse together with the participation of nitric oxide in integrating ganglionic
      cells.

PMID- 8742044
TI  - A benzodiazepine, chlordiazepoxide, blocks vasopressin and oxytocin release after
      footshocks but not osmotic stimulus in the rat.
AB  - Noxious as well as hypertonic stimuli potentiate vasopressin and oxytocin
      secretion in rats. Neurohypophysial vasopressin- and oxytocin-secreting neurons
      receive inhibitory synaptic inputs mediated by gamma-aminobutyric acid (GABA).
      Benzodiazepines modulate GABA-A receptor activity in a facilitatory fashion. It
      is thus possible that benzodiazepines suppress vasopressin and oxytocin release
      after noxious stimuli. To test this hypothesis, we investigated whether
      chlordiazepoxide impairs the enhanced release of vasopressin and oxytocin after
      noxious or hypertonic stimuli in male rats. Chlordiazepoxide (5-20 mg/kg, i.p.)
      blocked dose-dependently the vasopressin and oxytocin responses to footshocks.
      Chlordiazepoxide, however, did not impair the hormonal responses to hypertonic
      stimulus. The results demonstrate that chlordiazepoxide selectively prevents
      vasopressin and oxytocin release after noxious stimuli and therefore suggest that
      the sites of chlordiazepoxide actions are not on the vasopressin or oxytocin
      neurons in rats.

PMID- 8742045
TI  - Intrathecal administration of sodium nitroprusside, a nitric oxide donor,
      increases blood pressure in anesthetized rats.
AB  - The present study was performed to investigate the role of spinal nitric oxide
      (NO) in the central regulation of blood pressure (BP). Experiments were carried
      out in anesthetized artificially ventilated male Wistar rats. Intrathecal (i.t.)
      administration of drugs was made at the thoracic spinal level. I.t. injection of
      a NO donor, sodium nitroprusside (SNP; 1, 5, and 15 nmol) increased BP dose
      dependently. Intrathecal pretreatment of methylene blue (200 nmol) significantly
      attenuated the pressor response evoked by SNP (15 nmol, i.t.). I.t.
      administration of nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl
      ester (100 and 1000 nmol), caused decreases in BP. These results suggest that NO
      plays a tonic excitatory role in the central regulation of BP in the rat spinal
      cord.

PMID- 8742046
TI  - Action potentials in axonless horizontal cells isolated from the rabbit retina.
AB  - Axonless horizontal cells were enzymatically dissociated from the retinae of
      adult rabbits. Whole-cell patch-clamp recordings were made on dissociated cells
      and voltage- and ligand-induced currents were studied. When membrane potential
      was measured in the current-clamp configuration, current pulses injected into the
      cell induced repetitive action potentials. When the cells were depolarised by
      bath application of kainic acid (KA, 30 microM), a train of fast-repetitive
      action potential was evoked. Also, a slow long-lasting calcium action potential
      kept the cells depolarised long after the cessation of the KA application. These
      findings indicate for the first time that horizontal cells of the mammalian
      retina are able to produce trains of action potentials.

PMID- 8742047
TI  - Oxidative stress after acute and chronic application of beta-amyloid fragment 25
      35 in cortical cultures.
AB  - The aim of this work was to investigate whether free radical reactions play a
      role in beta-amyloid neurotoxicity. Rat cortical neurons were exposed acutely (24
      h) or chronically (3, 7 days) to beta-amyloid biologically active fragment beta
      25-35 (50 microM). In these conditions, where only the longest exposure induced
      neuronal death, superoxide dismutase activity was increased after acute exposure
      but no change was detected after chronic treatments, whereas a different pattern
      was observed for glutathione peroxidase. In the basal condition, there was an
      eight-fold increase in dichlorofluoroscein, used as peroxide production marker,
      in neuronal cells after 7 days treatment with beta 25-35. Moreover, the
      intracellular peroxide production induced by Fe2+/ascorbate stimulation was
      amplified by beta 25-35, increasingly up to 7 days of exposure, by which time the
      dichlorofluoroscein-stimulated levels were 33 times higher than in controls. In
      conclusion, our results show that oxidative stress and free radical production
      are linked to beta 25-35 exposure and may contribute to neurodegenerative events
      associated with beta-amyloid deposits in Alzheimer's disease.

PMID- 8742048
TI  - Antiepileptic effects of acidic fibroblast growth factor examined in kainic acid
      mediated seizures in the rat.
AB  - The possibility that exogenous recombinant human acidic fibroblast growth factor
      (rhaFGF) may have anticonvulsant properties was investigated in a model of
      temporal lobe epilepsy in awake rats. We found that after intraperitoneal
      injection of rhaFGF in kainic acid-treated rats, tonic-clonic convulsions and
      mortality were decreased by 74% and 77%, respectively. These results are
      consistent with previous studies showing a neuroprotective effect of FGF against
      insults to the brain and support a possible therapeutic role for FGF in the
      treatment of excitotoxic processes.

PMID- 8742049
TI  - Age-dependent reduction of hippocampal LTP in mice lacking N-methyl-D-aspartate
      receptor epsilon 1 subunit.
AB  - The effects of targeted disruption of the N-methyl-D-aspartate (NMDA) receptor
      epsilon 1 subunit gene were studied during the postnatal development of epsilon 1
      disrupted mutant mice. Using the mice at the ages of 2-3, 5-6 and 9-10 weeks, we
      examined NMDA receptor channel-mediated synaptic currents and long-term
      potentiation (LTP) in CA1 pyramidal neurons of hippocampal slices. NMDA receptor
      channel currents, expressed as the ratios to non-NMDA receptor channel currents,
      decreased with the age in both wild-type and mutant mice, but the values in the
      mutant mice was approximately half of those of the wild-type mice at all ages
      examined. The LTP in the mutant mice was also reduced, but in contrast to the
      NMDA receptor channel currents, the extent of the reduction in the LTP was age
      dependent. The reduction was marginal at the age of 2-3 weeks, and became
      progressively prominent to adulthood, with the potentiation being 26% of that of
      the wild-type mice at 9-10 weeks.

PMID- 8742050
TI  - Nineteenth century research on naturally occurring cell death and related
      phenomena.
AB  - Research on naturally occurring cell death is older than current opinion gives
      credit. More than 100 nineteenth century publications deal with it, and we review
      most of these. Soon after the establishment of the cell theory by Schleiden and
      Schwann, Carl Vogt (1842) reported cell death in the notochord and adjacent
      cartilage of metamorphic toads. Subsequent landmark discoveries included the
      massive cell death that occurs in pupating diptera (Weismann 1864), chondrocyte
      death during endochondral ossification (Stieda 1872), phagocytosis associated
      with cell death in the muscles of metamorphic toads (Metschnikoff 1883),
      chromatolytic (apoptotic) cell death in ovarian follicles (Flemming 1885), the
      reinterpretation of "Sarkoplasten" as "Sarkolyten" in metamorphic amphibia (Mayer
      1886), the programmed loss of an entire population of neurons in fish embryos
      (Beard 1889), the death of scattered myocytes and myofibres in mammalian muscle
      (Felix 1889), and the death of many motor and sensory neurons in chick embryos
      (Collin 1906). Other lines of nineteenth century research established concepts
      important for understanding cell death, notably trophic interactions between
      neurons and their targets, and intercellular competition.

PMID- 8742051
TI  - Synaptology of the olfactory bulb of an elasmobranch fish, Sphyrna tiburo.
AB  - The ultrastructure of the elasmobranch olfactory bulb was examined in order to
      determine the synaptology of the olfactory circuitry in the bonnethead shark,
      Sphyrna tiburo. The compartmentalization of the bulb, together with the lack of
      mitral cell basal dendrites, suggests a different way of performing lateral
      communication between mitral cells of the olfactory bulb. The results show that
      granule cells assume an important role by directly interlinking mitral cells. A
      corollary of this is the segregation of the input onto the mitral cell dendritic
      arborization: afferent fibers synapse onto the intraglomerular mitral terminals,
      whereas most local circuit interactions utilize extraglomerular synapses located
      on the shafts and the somas of the mitral dendrites. Therefore, the elasmobranch
      synaptic pattern is different from that of higher vertebrates; This might
      represent the use of a different neural route to achieve the same processing
      task.

PMID- 8742052
TI  - Immunohistochemical localization of estrogen receptors within aromatase
      immunoreactive neurons in the fetal and neonatal rat brain.
AB  - We elucidated the anatomical relationship between estrogen receptors and
      aromatase, the enzyme converting androgens to estrogens, in the fetal and
      neonatal rat brain by means of double immunohistochemical labeling, using
      antibodies against rat estrogen receptors and human placental aromatase
      cytochrome P450. Numerous aromatase-immunoreactive neurons were found in the
      medial preoptic area, the bed nucleus of the stria terminalis, the medial
      amygdaloid nucleus and the ventromedial nucleus. Estrogen receptors were also
      abundant in these areas. Most of the aromatase-immunoreactive neurons showed
      immunoreactivity for estrogen receptors in the medial subdivision of the bed
      nucleus of the stria terminalis and in the posterodorsal, division of the medial
      amygdaloid nucleus. There were also many double-labeled cells in the ventromedial
      nucleus. However, in the medial preoptic area the localization of aromatase
      immunoreactive neurons was distinct from that of neurons containing estrogen
      receptors. These results suggested that estrogens, which are converted from
      androgens in aromatase-containing neurons, are involved in the sexual
      differentiation of the brain through estrogen receptors within aromatase
      immunoreactive neurons in the bed nucleus of the stria terminalis, the medial
      amygdaloid nucleus and the ventromedial nucleus, but through estrogen receptors
      in aromatase-immunonegative neurons in the medial preoptic area.

PMID- 8742053
TI  - Relationship between altered axial curvature and neural tube closure in normal
      and mutant (curly tail) mouse embryos.
AB  - Neural tube defects, including spina bifida, develop in the curly tail mutant
      mouse as a result of delayed closure of the posterior neuropore at 10.5 days of
      gestation. Affected embryos are characterized by increased ventral curvature of
      the caudal region. To determine whether closure of the neuropore could be
      affected by this angle of curvature, we experimentally enhanced the curvature of
      non-mutant embryos. The amnion was opened in 9.5 day embryos; after 20 h of
      culture, a proportion of the embryos exhibited a tightly wrapped amnion with
      enhanced curvature of the caudal region compared with the control embryos in
      which the opened amnion remained inflated. Enhanced curvature correlated with a
      higher frequency of embryos with an open posterior neuropore, irrespective of
      developmental stage within the range, 27-32 somites. Thus, within this somite
      range, caudal curvature is a more accurate determinant for normal spinal
      neurulation than the exact somite stage. Enhanced ventral curvature of the curly
      tail embryo correlates with an abnormal growth difference between the
      neuroepithelium and ventral structures (the notochord and hindgut). We
      experimentally corrected this imbalance by culturing under conditions of mild
      hyperthermia and subsequently determined whether the angle of curvature would
      also be corrected. The mean angle of curvature and length of the posterior
      neuropore were both reduced in embryos cultured at 40.5 degrees C by comparison
      with control embryos cultured at 38 degrees C. We conclude that the sequence of
      morphogenetic events leading to spinal neural tube defects in curly tail embryos
      involves an imbalance of growth rates, which leads to enhanced ventral curvature
      that, in turn, leads to delayed closure of the posterior neuropore.

PMID- 8742054
TI  - Macrophages during avian optic nerve development: relationship to cell death and
      differentiation into microglia.
AB  - Cell death is frequent during the development of the nervous system. In the
      developing optic nerve of chicks and quails, neuroepithelial cell death was first
      observable on the third day of incubation, slightly after the first cell ganglion
      axons appeared in the stalk. Specialized phagocytes were observed within the
      stalk in chronological and topographical coincidence with cell death. These cells
      were identified as macrophages because of their morphological features, intense
      acid phosphatase activity and, in quail embryos, labeling with QH1, a monoclonal
      antibody recognizing quail hemangioblastic cells. Macrophages in areas of cell
      death were round and actively phagocytosed cell debris. We used electron
      microscopy and histochemical and immunocytochemical labeling to study macrophagic
      cells of the optic nerve in avian embryos of 3-6.5 days of incubation. As
      development proceeded, phagocytosing, round macrophages became ameboid
      macrophages that migrated from areas of cell death toward regions occupied by
      optic axonal fascicles. Macrophages in these locations were thin and elongated,
      with a few processes. To elucidate the final fate of macrophagic cells in the
      optic nerve, sections taken from older embryonic and hatched quails were stained
      with the QH1 antibody. On the 8th day of incubation some slightly ramified QH1+
      cells were present among axonal fascicles. In subsequent stages these cells
      increased in number and acquired more complex ramifications. In adult optic
      nerves, QH1+ cells had a small body and sent out slender processes, sometimes
      with secondary and tertiary branches, which were frequently orientated parallel
      to the course of the optic axons. These cells were considered to be microglial
      cells. The appearance of macrophages within the developing optic nerve at the
      same time as neuroepithelial cell death suggests that cell death influences the
      recruitment of macrophages into the nerve. When macrophages reach the areas
      invaded by optic axonal fascicles, they undergo structural and probably also
      physiological changes that appear to signal differentiation into microglia.

PMID- 8742055
TI  - Vitamin D target systems in the brain of the green lizard Anolis carolinensis.
AB  - Autoradiographic mapping criteria were employed to identify and localize specific
      high affinity binding sites (receptors) for the steroid hormone 1,25
      dihydroxyvitamin D3 (1,25-D3) in the brain of Anolis carolinensis. In female and
      male lizards binding of tritiated 1,25-D3 occurred in identical regions of the
      fore-, mid-, and hindbrain, similar to findings in other species. There was a
      band of intensely labeled neurons forming a continuum from the n. accumbens, n.
      striae terminalis, the striatum, and extending into the amygdala. Target areas
      with high to intermediate labeling intensities were present in many other regions
      of the brain and single, small target cells were found throughout the organ. Some
      cells in the pituitary and pineal were labeled and also cells associated with the
      meninges, choroid plexuses and ependyma. The differential labeling suggests the
      existence of different 1,25-D3-responsive systems. One of the conspicuous "high
      capacity-high affinity systems" is found in the n. accumbens-n. striae terminalis
      and the amygdala. Most of the cerebral target regions for vitamin D correspond to
      those known for gonadal steroids, and the seasonal steroid 1,25-D3 may therefore
      act in conjunction with gonadal steroids in this seasonally breeding reptile.

PMID- 8742056
TI  - Localization of nitrergic neuronal and non-neuronal cells in the ultimobranchial
      glands of the chicken.
AB  - The ultimobranchial glands of 20 chickens, aged 2-3 months, were investigated for
      their nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d)
      reactivity and the distribution of nitric oxide synthase (NOS), using NADPH-d
      histochemistry and NOS immunocytochemistry respectively. Formazan, the blue
      reaction product of NADPH-d, was localised in the neuronal cell bodies and nerve
      fibres. Most of the cell bodies were found in the parenchyma. Some of them
      occurred in the wall of the ultimobranchial cysts, and a few in the immediate
      vicinity of the blood vessels. Labelled nerve fibres mostly travelled with blood
      vessels, while few of them appeared in the cystic lining. In addition to neuronal
      profiles, some C cells, cystic lining, and vascular endothelium were also
      labelled. NOS staining was found in neuron-like cells and fibres that were
      confirmed as neurons in adjacent sections stained with antibodies against neuron
      specific enolase. It was also detected in cystic lining and in some C cells, but
      not in vascular endothelium. The distribution patterns of NADPH-d and NOS suggest
      that NO may play a role in the regulation of the secretory activity of and the
      blood flow through the ultimobranchial glands.

PMID- 8742058
TI  - Lymph pathways associated with three types of follicle structure found in gut
      associated lymphoid tissue of horse ileum.
AB  - In the horse ileum, lacteals in the villi are continuous with prelymphatic
      intercellular channels and a plexus of lymphatic sinuses in the lamina propria
      that encircle the domes of the follicle/dome structures and proprial follicles.
      These sinuses may act as the major entry site for many of the lymphocytes
      migrating from gut-associated lymphoid tissue via the lymphatic system. Vessels
      from this plexus penetrate the muscularis mucosae and lymph flows into lymphatic
      vessels within the interfollicular tissue between the follicles of both
      follicle/dome structures and lymphoglandular complexes (LGCs). No lymphatic
      vessels leave the follicles, but intercellular pathways of the follicles are
      continuous with those in the surrounding interfollicular tissue and follicular
      sinuses around the base of the follicles. These pathways appear to provide the
      only available lymphatic route for lymphocytes leaving LGCs to enter the
      lymphatic system. Lymph from the interfollicular tissue enters deep submucosal
      lymphatic vessels, containing prominent valves, which drain into other vessels
      transporting lymph from the surface of the ileum.

PMID- 8742057
TI  - Long-term structural alterations to endothelial cells in vein-to-artery grafts: a
      quantitative electron microscopic study.
AB  - The intracellular structure of endothelium lining vein-to-artery grafts in rats
      was analysed, using transmission electron microscopy and morphometry, to
      determine the ultrastructural adaptations of endothelial cells in this altered
      vascular environment. Autogenous 4-mm sections of iliolumbar veins were inserted
      microsurgically into the left common iliac arteries of 16 male Wistar rats. At 3,
      6, 26 and 52 weeks the cytoplasmic-vesicular, mitochondrial and rough endoplasmic
      reticular contents of endothelial cells lining the grafts, the opposite iliac
      arteries and the remaining ilio-lumbar veins were analysed morphometrically.
      There was a significant increase in the amount of all these cytoplasmic
      structures in endothelial cells at 3, 6 and 26 weeks, at 52 weeks there was also
      a significant increase in the volumes of mitochondria and cytoplasmic vesicles,
      but not in rough endoplasmic reticulum. It was concluded that the ultrastructure
      of endothelial cells lining these grafts is changed chronically after graft
      insertion, and we propose that this may be attributable to altered haemodynamic
      stresses within the graft.

PMID- 8742059
TI  - Lamina propria of sex cords in human fetal testis: an immunohistological and
      stereological study.
AB  - Testicular peritubular cells are located in the lamina propria of seminiferous
      tubules. These cells, significantly contributing to the basal membrane of
      seminiferous epithelium, have been studied in a number of species. However, there
      is a lack of data on the development of the lamina propria in the human testis.
      The aim of our survey was to investigate the characteristics of the lamina
      propria and, in particular, peritubular cells in the fetal human testes by
      immunohistological and stereological methods. Therefore, testes (14-39 weeks of
      gestation, n = 45) were dissected and fixed in a 4% buffered paraformaldehyde
      solution. Several pieces of each testis were embedded in paraffin and processed
      for immunohistochemical and stereological analysis. All investigated testes have
      shown sex cords in the process of development and differentiation.
      Morphologically, peritubular cells in the lamina propria can be divided into two
      types: fibroblast-like (FL) and myoid-like (ML) type (cells which much resemble
      mature myoid cells). By immunohistochemistry, both FL and ML cells are found to
      be strongly positive for the intermediate filament desmin, but negative for alpha
      smooth actin. While FL cells intensively express Ki-67 demonstrating
      proliferative activity, ML cells are found to be negative. The basement membrane
      of sex cords as well as the blood vessels of the interstitium show strong
      positivity to collagen IV and laminin. Concerning the correlation between the
      appearance of the investigated antigens with the gestational age, all antigens
      have been expressed (in the manner described above) already in the 14th week of
      gestation. The stereological analysis of the number (Nv) and volume (Vv) of
      peritubular cells indicates a pulsatile development of these cells in the lamina
      propria of the human fetal testis. While the stereological variables determined
      for FL cells show a gradual decrease, the same variables determined for ML cells
      demonstrate a successive increase. It appears that the lamina propria of the
      fetal human testes shares many of the properties previously discovered in
      rodents.

PMID- 8742060
TI  - Partial N-terminal amino acid sequence of the anti-neoplastic urinary protein
      (ANUP) and the anti-tumour effect of the N-terminal nonapeptide of the unique
      cytokine present in human granulocytes.
AB  - The N-terminal amino acid sequence of the anti-neoplastic urinary protein (ANUP),
      a unique cytokine present in human granulocytes, was determined to be: Pyroglu
      Leu-Lys-X-Tyr-Thr-X-Lys-Glu-Pro-Met-Thr-Ser(Thr)-Ala-Ala... This sequence showed
      no significant homology with any other protein when used in database searches.
      Furthermore, a synthetic nonapeptide corresponding to the first nine residues,
      with Cys in positions 4 and 7, was found to be a biologically active in vitro
      anti-tumour agent. An alternate method for the purification of ANUP to that
      previously reported is also presented. This method involves differential Amicon
      Diaflo membrane filtration.

PMID- 8742061
TI  - Expression and co-cytokine function of murine thioredoxin/adult T cell leukaemia
      derived factor (ADF).
AB  - Human ADF (adult T cell leukaemia-derived factor), an isoform of thioredoxin,
      promotes proliferation of certain human lymphoid cell lines and is involved in
      many thiol-dependent reducing reactions. To study functional aspects of the
      murine homologue, we established inducible overexpression of murine ADF in E.
      coli and a purification method which led to an apparently homogeneous 14 kDa
      protein. This recombinant ADF was tested in proliferation assays with murine Th2
      cells (D10.G4.1) and CTLL-2 cells. In synergy with IL-2, IL-4, IL-7 and IL-9 ADF
      displayed co-cytokine activity. These proliferative effects were neutralized by
      an affinity-purified polyclonal rabbit anti-ADF antiserum. The effects of ADF
      were critically dependent on the presence of 2-mercaptoethanol. Bacterial
      thioredoxin had similar effects on the proliferation of murine T cells. Thus, the
      thiol-related reducing capacity of these proteins is essential for their growth
      promoting activity. As investigated at the levels of mRNA and protein in several
      murine cell clones and lines as well as in mouse tissues ADF is expressed
      ubiquitously. Finally it could be demonstrated by competitive PCR that in
      contrast to cytokine mRNAs (e.g. IL-4 and IL-13) the expression of ADF mRNA in
      murine Th2 clones and spleen cells is not influenced by stimulation of these
      cells through the T cell receptor complex. Murine ADF therefore represents a
      protein constitutively expressed in a wide variety of cells with the capacity to
      enhance the proliferative effect of several cytokines on murine T cells.

PMID- 8742062
TI  - Avian stem cell factor (SCF): production and characterization of the recombinant
      His-tagged SCF of chicken and its neutralizing antibody.
AB  - Recombinant chicken stem cell factor (SCF) was produced in bacteria as a
      histidine-tagged protein (His delta SCF) and purified by affinity chromatography
      on an Ni(2+)-NTA agarose column. His delta SCF is devoid of signal peptide and
      transmembrane domains and therefore mimics a soluble form of SCF. We demonstrate
      that the factor is biologically fully active in supporting sustained
      proliferation of SCF-dependent red blood progenitor cells of chicken in vitro.
      Polyclonal SCF-specific antibodies were raised in rabbits and shown to display
      potent SCF-neutralizing activity. Thus, recombinant chicken His delta SCF
      together with the SCF-specific antibody provide valuable tools for studying the
      role of SCF and c-kit receptor in development, growth and differentiation of
      avian haematopoietic cells.

PMID- 8742063
TI  - Complementary organ expression of IL-1 vs. IL-6 and CSF-1 activities in normal
      and LPS-injected mice.
AB  - The specific expression of pro-inflammatory cytokines may affect the functioning
      of organs in different ways. The results of specific cytokine bioassays used in
      this study show a distinct pattern of tissue expression of IL-1 IL-6 and CSF-1.
      Cytokine activity was assessed in conditioned media (CM) and lysates (LYS),
      obtained from different organs of control or lipopolysaccharides (LPS)-injected
      mice; LPS representing a potent inflammatory stimulus. Low constitutive levels of
      IL-1 could be demonstrated only in CM/LYS from organs with lymphoreticular
      function, such as the liver, spleen, intestine and lungs. On the other hand, IL-6
      and CSF-1 were mainly detected in the CM (and not in lysates) of organs, such as
      the heart, kidneys, muscle and brain. LPS injection basically resulted in an
      accentuated form of the constitutive pattern. CSF-1 displays a similar pattern of
      expression to that of IL-6, best detected in CM after LPS stimulation. Thus, a
      mirror-image relationship emerges between the patterns of IL-1 and IL-6/CSF-1
      expression in two groups of organs: those with lymphoreticular function, which
      manifest high IL-1 and low IL-6/CSF-1 activity, as compared to organs
      characterized by highly specialized and potentially vulnerable functions (such as
      the heart, brain, muscle and kidney), which exhibit high IL-6/CSF-1 and low IL-1
      activity. Due to their defensive functions, lymphoreticular organs, which are in
      charge of the 'gates of entry' to the body, mount extensive IL-1-mediated
      inflammatory responses, even at the cost of possible tissue-damage. On the other
      hand, the more vulnerable internal organs mount IL-6/CSF-1-mediated responses
      which are milder and bear less potential for tissue damage. The distinct patterns
      of expression of pro-inflammatory cytokines in different organs, at steady state
      or under inflammatory conditions, may shed light on tissue characteristic
      homeostatic and defence mechanisms.

PMID- 8742064
TI  - Cytokine mRNA levels in unmanipulated (ex vivo) and in vitro stimulated monkey
      PBMCs using a semi-quantitative RT-PCR and high sensitivity fluorescence-based
      detection strategy.
AB  - To investigate the spectrum of cytokines expressed by peripheral blood
      mononuclear cells (PBMC) from cynomolgus macaques (Macaca fascicularis), we used
      a semi-quantitative RT-PCR to determine levels of mRNA coding for IL-1 beta, IL
      2, IL-4, IL-6, IL-10, IFN-gamma, and TNF-alpha. The PCR products were labelled
      and quantified using a new fluorescent tag TOTO-1 (thiazole orange dimer) and an
      automated fluorescence-based electrophoretic instrument. Using this assay, the
      base line levels of cytokine mRNA expression in unmanipulated PBMCs (ex vivo)
      from 10 healthy monkeys were compared with the mRNA levels for the same cytokines
      in PBMC samples from two pre-immunized monkeys following culture with previously
      defined optimal concentrations of purified protein derivative (PPD), tetanus
      toxoid (TT) and the mitogen concanavalin A (con-A). While transcripts or IL-2, IL
      4 and IFN-gamma were either low or not detected in unmanipulated PBMCs, varying
      levels of IL-1 beta, IL-5, IL-10, and TNF-alpha were readily detected in the same
      samples. With the exception of IL-10, the mitogen con-A induced the highest
      levels of cytokine expression, followed by levels induced by culture with TT. The
      levels of cytokine expression induced by PPD however, were not significantly
      elevated, despite the fact that the cells showed marked proliferative responses.
      This assay is a simple and convenient method for evaluating the levels of
      cytokine expression in small PBMC samples and will allow for the concurrent
      evaluation of immune profiles with functional immune analyses.

PMID- 8742065
TI  - Ex vivo effects of macrophage colony-stimulating factor on human monocyte
      activity against fungal and bacterial pathogens.
AB  - The ex vivo effects of macrophage colony-stimulating factor (M-CSF) on antifungal
      and antibacterial activities of human elutriated monocytes were studied. Cells
      were isolated prior to the initiation of therapy, on day 3 and at week 7, in six
      patients with an advanced malignancy receiving M-CSF in a phase I study.
      Superoxide anion production by monocytes in response to N-formyl methionyl leucyl
      phenylalanine was enhanced at day 3 of therapy (P = 0.011). In addition, at day
      3, fungicidal activity against blastoconidia of Candida albicans was enhanced by
      M-CSF treatment (P = 0.026), whereas antifungal activity against hyphae of
      Aspergillus fumigatus was not significantly changed. Bactericidal activity
      against Staphylococcus aureus was increased at day 3 (P = 0.004). By Northern
      blot analysis, M-CSF does not upregulate the expression of components of the
      NADPH-oxidase, the multicomponent enzyme system responsible for generation of
      superoxide radicals by monocytes. Instead, the predominant effect of M-CSF on
      circulating monocytes is probably a post-transcriptional effect. In conclusion,
      these findings suggest that administration of M-CSF to patients may enhance
      microbicidal activities and thus may provide a useful adjunct to conventional
      antimicrobial therapy.

PMID- 8742066
TI  - IL-4, IL-10 and IFN-gamma have distinct, but interacting, effects on
      differentiation-induced changes in TNF-alpha and TNF receptor release by cultured
      human monocytes.
AB  - Monocytes cultured in vitro differentiate to a macrophage-like phenotype and
      undergo functional changes, including reduced capacity for release of TNF-alpha
      and the soluble p55 receptor for TNF (sTNF-R55) but enhanced capacity for release
      of the soluble p75 receptor (sTNF-R75). The cytokines IL-4 and IL-10 act on
      monocytes to suppress the release of pro-inflammatory cytokines, including TNF
      alpha, and to influence the release of sTNF-R. We therefore investigated the
      influence of differentiation over 15 days in vitro on the spontaneous and LPS-
      and IFN-gamma-induced release of TNF-alpha and sTNF-R from human monocytes and
      examined the actions of IL-4 and IL-10 on these. Unstimulated monocytes did not
      release TNF-alpha at any stage but released progressively larger amounts of sTNF
      R75 with time. LPS-stimulated release of TNF-alpha declined substantially after
      the first day and was consistently suppressed by IL-10 and IL-4 but increased by
      IFN-gamma. Monocytes cultured with IL-10 released more sTNF-R75 at all times and
      expressed more mRNA for TNF-R75 at day 8. LPS stimulation consistently enhanced
      both spontaneous and IL-10-augmented release of sTNF-R75, whilst IFN-gamma co
      stimulation consistently suppressed them. The influence of IL-4 on sTNF-R75
      release, however, depended qualitatively on both the length of time in culture
      and on conditions of stimulation. The effects of LPS and IFN-gamma on TNF-alpha
      and sTNF-R75 release were progressively lost with increasing time in culture in
      the presence of IL-4. sTNF-R55 was not detectable after the first day of culture
      under any of these conditions. IL-4, IL-10 and IFN-gamma therefore have distinct,
      but interacting, effects on the balance between TNF-alpha and sTNF-R75 release by
      maturing monocytes. These interactions may be relevant to the pathogenesis or
      treatment of TNF-alpha-mediated diseases, where sTNF-R may act to neutralize or
      stabilise TNF, thereby modifying biological activity.

PMID- 8742067
TI  - TGF-beta 1, IL-10 and IL-4 differentially modulate the cytokine-induced
      expression of IL-6 and IL-8 in human endothelial cells.
AB  - Multiple cytokines and growth factors are present at sites of inflammation, and
      each of these can potentially influence the nature of the inflammatory response.
      Vascular endothelial cells (ECs) must integrate the signals generated by these
      multiple factors to effectively regulate the immune response and homeostasis. IL
      6 and IL-8 and endothelial-derived products which play an important role as
      regulators of these processes. As a model for how ECs respond to signals from
      multiple cytokines, we have examined the effects of pretreatment with TGF-beta 1,
      IL-10 or IL-4 on TNF-alpha, IL-1 beta- or LPS-induced expression of IL-6 and IL-8
      in human umbilical vein endothelial cells (HUVEC). Treatment of HUVEC with TGB
      beta 1 or IL-10 significantly inhibited, but did not completely abolish, the TNF
      alpha-, IL-1 beta- or LPS-induced expression of IL-6 and IL-8 protein. Maximal
      inhibition was achieved with physiologically relevant doses (1-2 ng/ml) of either
      TGF-beta 1 or IL-10. The inhibitory effects of TGF-beta and IL-10 were additive
      in nature. In contrast, pretreatment with IL-4 amplified the production of IL-6
      in TNF-alpha-, IL-1 beta- or LPS-activated ECs, but inhibited IL-8 expression.
      Addition of TGF-beta 1 completely reversed the effects of IL-4 on IL-6
      expression, whilst augmenting inhibition of IL-8. These studies demonstrate that
      multiple cytokines can act in concert to differentially regulate the endothelial
      expression of cytokines important to the inflammatory response. Modulation of
      endothelial cytokine production may contribute to the progression or resolution
      of the inflammatory response.

PMID- 8742068
TI  - A sensitive human cell line based bioassay for megakaryocyte growth and
      development factor or thrombopoietin.
AB  - We have developed a simple, rapid, sensitive bioassay for megakaryocyte growth
      and development factor (MGDF) or thrombopoietin (TPO) based on its ability to
      stimulate the proliferation of the human megakaryoblastic cell line MO7e. The
      bioassay takes only 24 h, is reproducible and sensitive to less than 10 pg/ml of
      MGDF. It can be made specific for MGDF by including neutralizing antibodies
      specific for MGDF, and is suitable for detection of MGDF in both plasma and serum
      samples.

PMID- 8742069
TI  - Expression of cytokines and their receptors by psoriatic fibroblast. I. Altered
      IL-6 synthesis.
AB  - Interleukin(IL-)6 is overproduced in psoriatic lesions. We investigated the
      contribution of dermal fibroblasts to the local IL-6 production. Fibroblasts
      (passageno. 2 to 6) derived from lesional psoriatic (PP) and normal human (NN)
      skin were used to analyse the secretion of IL-6, and the related cytokines IL-1,
      IL-8 and TNF-alpha, and the expression of their corresponding mRNA by bioassay,
      ELISA and Northern hybridization, respectively. PP fibroblasts cultured under
      serum-free conditions produced increased amounts of bioactive IL-6 when compared
      to NN fibroblasts. Differences were partially restored in the presence of growth
      factors or serum. The serum-induced IL-6 production reached a maximum within 24 h
      after seeding and remained unchanged in PP fibroblasts, whereas comparable
      amounts of IL-6 were produced only 6 days later in NN fibroblasts. There was a
      clear expression of IL-6 mRNA in both types of fibroblasts under serum-free
      conditions. Unexpectedly, fetal calf serum, inactivated fetal calf serum as well
      as human serum completely inhibited the expression of IL-6 mRNA in all the PP
      fibroblast cultures investigated. NN fibroblasts were clearly less sensitive to
      this inhibiting effect of serum. Furthermore, medium supplemented with serum-free
      component or calcium also repressed IL-6 mRNA expression in PP fibroblasts in
      contrast to NN fibroblasts. Cycloheximide fully restored the repressing effect of
      serum indicating that serum induced a labile repressor protein. PP and NN
      fibroblasts produced negligible amounts of IL-1 and TNF-alpha, but the production
      of IL-8, however, was comparable to that of IL-6. Our results show a differently
      regulated IL-6 synthesis in PP fibroblasts in vitro, suggesting an active
      contribution of dermal fibroblasts to the local IL-6 production in psoriasis.

PMID- 8742070
TI  - Expression of cytokines and their receptors by psoriatic fibroblasts. II.
      decreased TNF receptor expression.
AB  - Psoriatic fibroblasts produce enhanced amounts of IL-6 in vitro. This state of
      activation may reflect an altered expression of cytokine receptors, involved in
      auto/paracrine induction of IL-6. Cultures of dermal fibroblasts derived from
      lesional psoriatic (PP) and normal control (NN) skin were therefore analysed for
      their ability to bind biotinylated recombinant human cytokines using flow
      cytometry. PP and NN fibroblasts bound negligible amounts of IL-1 alpha and IL-1
      beta, but clearly bound IL-4, IL-6 and TNF-alpha. Serum upregulated the number of
      NN fibroblasts which bound TNF-alpha, and to a lesser extent IL-6, but not the
      number of binding sites per cell. In contrast, this upregulation was
      significantly less in PP fibroblasts. This was not a result of differences in
      growth characteristics, receptor occupancy or an inability of stimulated PP
      fibroblasts to bind TNF-alpha. Immunocytochemistry of cells grown on slides
      showed that the TNF receptor type 1 (TNFR1, p55) was the predominant receptor in
      NN fibroblasts and was localized to the nucleus of cytoplasma. The expression of
      TNFR1 was clearly decreased in PP fibroblasts, which confirmed the binding
      studies. A slow and serum-induced shedding of TNFR1 was observed, but not of the
      TNFR2 (p75), in both types of fibroblasts. Confluent multi-passaged PP
      fibroblasts display both a decreased TNFR expression as well as an enhanced IL-6
      production under serum conditions. These inherent abnormalities of PP fibroblasts
      imply the involvement of dermal fibroblasts in the maintenance of chronic
      inflammation in psoriasis.

PMID- 8742071
TI  - RANTES chemokine expression in diseased and normal human tissues.
AB  - RANTES is a member of a large family of cytokines, called chemokines, which are
      thought to play a regulatory role in inflammatory processes. We have made
      recombinant human RANTES protein which was used to generate a panel of anti
      RANTES monoclonal antibodies. Following characterization, select anti-RANTES
      monoclonal antibodies were used for immunohistologic staining of a large panel of
      normal, diseased and fetal tissue sections. Diseased tissues included eleven
      lymphomas and eight renal tumors. Most tissues were also tested in parallel for
      RANTES mRNA by in situ hybridization using RANTES mRNA specific oligomeric
      probes. As expected, most normal adult tissues contain few, if any, RANTES
      positive cells. In contrast, RANTES expression dramatically increases in
      inflammatory sites. In addition, megakaryocytes, some tumours, and select fetal
      tissues express high levels of RANTES message and protein. These results indicate
      a wider expression of RANTES than previously appreciated and suggest multiple
      physiologic roles for this soluble factor.

PMID- 8742072
TI  - Cytokine production by SV40-transformed adherent synovial cells from rheumatoid
      arthritis patients.
AB  - We examined the mRNA levels for various cytokines, including IL-1 alpha, IL-1
      beta, TNF alpha, TGF-beta 1, GM-CSF, IL-6, IL-8, bFGF, PDGF-A, PDGF-B and IL-1ra,
      and IL-1 beta converting enzyme, and the protein levels of some of these
      cytokines in 19 SV40-transformed synovial cell clones. Among those tested, the
      mRNA levels for IL-6, bFGF and PDGF-A in rheumatoid arthritis (RA) cell clones
      were greater than those in non-RA cell clones. Moreover, except for one
      osteoarthritis (OA) cell clone, the mRNA levels for IL-8 in RA cell clones were
      also greater than those in non-RA cell clones. Although the protein levels were
      not always correlated with the mRNA levels, the exception being the same OA cell
      clone, the protein levels of cytokines, such as IL-1 alpha, IL-1 beta, IL-6 and
      IL-8, in RA cell clones were greater than those in non-RA cell clones. TNF-a was
      not detected in any cells tested at either the mRNA or the protein level. TNF
      alpha upregulated the expression of GM-CSF mRNA in both RA cell clones and one OA
      cell clone, but not in the other OA cell clone or the normal cell clone. Taken
      together, these SV-40 transformed synovial cell clones retained many of the
      original characteristics in terms of cytokine production.

PMID- 8742073
TI  - Viscosimetric affinity assay.
AB  - Affinity ligands and/or affinity receptors may be quantified by a viscosimetric
      assay which can be carried out with a simple technique and has the potential of
      broad applications. The viscosimetric affinity assay is based on the high
      contribution of affinity bonds to the viscosity of an aqueous dispersion of a
      hydrocolloid that is bearing affinity ligands. In dispersions of such sensitive
      hydrocolloids at a concentration above the overlapping point, agglutination is
      not possible and the modulation of viscosity by the formation or dissociation of
      intercolloidal affinity bonds may be several orders of magnitude larger than the
      basic viscosity measurable in the absence of intercolloidal affinity bonds. If
      dispersions (30 g liter-1) of branched dextran with high molecular weight were
      used as reagent for concanavalin A (Con A), the Con A concentration necessary for
      a significant rise in viscosity was decreased with increasing colloid size. The
      viscosity of dispersions containing both a ligand-bearing high-molecular-weight
      dextran and an appropriate polyvalent receptor protein (lectin or antibody)
      showed a dependence on the concentration of free ligands (sugars or insulin)
      according to the law of mass action. In this competitive mode the viscosimetric
      affinity assay seems to be well adaptable to many analytical problems.

PMID- 8742074
TI  - Direct continuous fluorometric assay for monoamine oxidase B.
AB  - The first direct and continuous fluorometric assay for monoamine oxidase B (MAO
      B) has been developed. E-2,5-Dimethoxycinnamylamine hydrochloride was designed
      and synthesized and was found to be an excellent substrate for MAO B (Km = 218
      microM, Kcat = 435 min-1). This compound has an intense purple fluorescence when
      irradiated at lambda ex = 343 nm (lambda em = 393 nm) in Tris buffer, pH 9.0, or
      sodium phosphate buffer, pH 7.2, but under the same conditions, the corresponding
      aldehyde, the product of the MAO-catalyzed oxidation of E-,5
      dimethoxycinnamylamine hydrochloride, does not fluoresce. The activity of MAO B,
      therefore, can be determined efficiently and rapidly by continuously following
      the decrease in fluorescence at 393 nm at enzyme concentrations as low as 100 nM.
      The change in fluorescence is linear up to a substrate concentration of 500
      microM.

PMID- 8742075
TI  - Antigen--antibody interactions in the reverse micellar system: quenching of the
      fluorescence of fluorescein-labeled atrazine by antibodies against atrazine.
AB  - This work presents a new method for performing homogeneous fluoroimmunoassay in
      apolar organic media, quenching fluoroimmunoassay (QFIA). This method is based on
      utilization of the reverse micellar system of Aerosol OT (AOT) in n-octane as a
      medium for the analysis of compounds with low water solubility. It is shown using
      the system for determination of a hydrophobic pesticide atrazine as an example.
      The conjugate of atrazine with fluorescein (FA) serves as a label for
      fluorescence detection of antigen-antibody interaction in the reverse micellar
      system. The fluorescence quantum yield of this compound drastically depends on
      the micro-environment of the label in the reverse micelle system. Specifically,
      the binding of this conjugate with the antibodies solubilized in the reverse
      micelles results in fluorescence quenching. We found that quenching efficiency
      depends on the properties of the reverse micellar system (surfactant
      concentration, hydration degree w0, w0 = [water]/[surfactant], etc.). The optimal
      conditions for quenching of FA fluorescence by antibodies in reverse micelles of
      AOT in n-octane are low surfactant concentration and hydration degree, allowing
      one to get large reversed micelles (w0 = 15-20) capable of retaining solubilized
      antibodies. Addition of free atrazine results in displacement of the conjugate
      and restoration of its fluorescence. The sensitivity of the analysis to atrazine
      is only 10 times less than that of the commonly used method of homogeneous
      immunoassay, polarization fluoroimmunoassay, in aqueous solution using the same
      antibodies and conjugate. The advantage of QFIA in reverse micelles is that the
      analyte can be added when dissolved in nonpolar organic solvent.

PMID- 8742076
TI  - Quantitation of L-amino acids by substrate recycling between an aminotransferase
      and a dehydrogenase: application to the determination of L-phenylalanine in human
      blood.
AB  - A spectrophotometric recycling assay for the quantitation of L-phenylalanine (and
      phenylpyruvate) has previously been reported (Cooper et al., Anal. Biochem. 183,
      210-214, 1989). The procedure involves the coupling of bacterial phenylalanine
      dehydrogenase with rat kidney cytosolic glutamine transaminase K. The latter
      enzyme possesses high affinity for phenylpyruvate. Recycling results in a > or =
      50-fold increase in sensitivity over that of a conventional spectrophotometric
      "end point" analysis procedure. The spectrophotometric recycling procedure has
      now been adapted to the measurement of L-phenylalanine in microliter quantities
      of human blood. This procedure is 10 times more sensitive than provided by a
      commercial kit for the spectrophotometric measurement of L-phenylalanine in human
      blood. Moreover, the present results suggest that the recycling procedure adapted
      for fluorometry will be even more sensitive. By use of suitable dehydrogenases
      and amino acid aminotransferases it should be possible to quantitate amino acids
      (in addition to phenylalanine) in small quantities of human blood.

PMID- 8742077
TI  - A solid-phase assay for the determination of protein tyrosine kinase activity of
      c-src using scintillating microtitration plates.
AB  - A solid-phase assay for the determination of protein tyrosine kinase (PTK)
      activity has been developed. The transfer of 33PO4 from ATP to the synthetic
      substrate poly(Glu, Tyr) 4:1 attached to the bioactive surface of scintillating
      microtiter plates served as the basis to evaluate enzyme activity. The procedure
      eliminates detection with phosphotyrosine antibodies, tedious separation of
      phosphorylated peptides with phosphocellulose membranes, and extensive washing
      steps. For these reasons, the traditionally time-consuming procedure can be
      performed with a simple three-step protocol. The method is highly accurate,
      rapid, and robotics friendly. The advantages over existing assays make this
      procedure especially suited for high throughput applications.

PMID- 8742078
TI  - Continuous beds for microchromatography: reversed-phase chromatography.
AB  - Simple and cost-effective methods for the preparation of microcolumns (i.d. 0.025
      0.32 mm) for reversed-phase chromatography are described. The procedure includes
      (1) synthesis in the column tube of a continuous bed matrix from a monomer
      solution (piperazine diacrylamide, methacrylamide) containing allyl glycidyl
      ether and 2-hydroxyethyl methacrylate and (2) linking of C18 ligands by reacting
      1,2-epoxyoctadecane with the epoxy and hydroxy groups in the matrix. The
      derivatization can be accomplished within 20 min. The columns prepared in this
      way showed high performance in the separation of proteins and peptides and
      permitted short analysis times (100 s).

PMID- 8742079
TI  - Fluorometric titration of the mitochondrial ADP/ATP carrier protein in muscle
      homogenate with atractyloside derivatives.
AB  - We describe here the chemical synthesis of the novel methylanthraniloyl (Mant-)
      derivative of atractyloside (ATR), which is a specific inhibitor of the
      mitochondrial ADP/ATP carrier. The spectral properties of Mant-ATR and naphthoyl
      ATR (N-ATR) are analyzed. Both derivatives bind to the membrane-bound ADP/ATP
      carrier at the same sites as ATR and carboxyatractyloside (CATR). When Mant-ATR
      and N-ATR are displaced by CATR, their fluorescence emissions are decreased and
      increased, respectively. These fluorescence changes allow the titration of the
      CATR binding sites and therefore the quantitation of the amount of ADP/ATP
      carrier protein in a biological preparation. The validity of the fluorometric
      titration was tested with beef heart mitochondria and confirmed by binding assays
      using radioactive ATR. The fluorometric method was applied to rabbit skeletal
      muscle homogenate and the results of titration were confirmed by binding assays
      of radioactive ATR. The reliability of the fluorometric method was assessed by
      comparing the amounts of CATR binding sites and the content of heme aa3 in muscle
      homogenates and in isolated mitochondria from the same homogenates. Because of
      its high sensitivity, the fluorometric titration of the ADP/ATP carrier requires
      small amounts of tissue. Mant-ATR and N-ATR can therefore be considered as
      convenient, reliable, and sensitive probes to quantify the amount of ADP/ATP
      carrier and detect a putative carrier protein deficiency in biopsy samples from
      human patients suffering from myopathies with no clear identified etiology.

PMID- 8742080
TI  - Selective detection and site-analysis of O-GlcNAc-modified glycopeptides by beta
      elimination and tandem electrospray mass spectrometry.
AB  - Over the past decade, a number of nuclear and cytoplasmic proteins have been
      identified that are modified by single N-acetylglucosamine residues attached to
      the hydroxyl side chain of serines or threonines (O-GlcNAc). O-GlcNAc is a
      dynamic modification and therefore may act in a regulatory capacity analogous to
      phosphorylation. To undertake site-directed mutagenesis studies of O-GlcNAc's
      function, it is necessary to identify the sites of glycosylation on various
      proteins. The current method of site mapping, which involves
      galactosyltransferase labeling, generation of glycopeptides by proteolysis,
      purification by several rounds of HPLC, and gas-phase and manual Edman
      sequencing, is very tedious and requires about 10 pmol of pure, labeled
      glycopeptide. In this report, synthetic glycopeptides were generated and used to
      demonstrate that O-GlcNAc-modified peptides can be rapidly identified in complex
      mixtures by HPLC-coupled electrospray mass spectrometry due to the partial loss
      of the O-linked glycan (204 amu) at a modest orifice potential. Furthermore, the
      exact site of glycosylation was directly identified in the low picomole range by
      collision-induced dissociation (CID) of the glycopeptide after removal of the O
      GlcNAc by alkaline beta-elimination. The conversion of glycosylserine to 2
      aminopropenoic acid (2-ap) by beta-elimination both decreased the mass of the
      glycopeptide by 222 amu and resulted in a CID fragment ion representing the loss
      of 69 amu (2-ap) instead of 87 amu (Ser) at the position of the glycosylserine.
      Finally, we tested this method on an identical synthetic, alpha-linked O-GalNAc
      modified peptide. Like O-GlcNAc, the O-GalNAc moiety was selectively removed at a
      modest orifice potential; however, the beta-elimination conditions that
      efficiently removed the O-GlcNAc only liberated about 20% of the O-GalNAc. We
      conclude that the selectivity and the sensitivity of this method will make it a
      powerful tool for determining the sites of O-GlcNAc modification on proteins of
      low abundance such as transcription factors and oncogenes.

PMID- 8742081
TI  - A rapid formaldehyde assay using purpald reagent: application under periodation
      conditions.
AB  - Measurement of formaldehyde is encountered in a broad range of applications
      including the wine and alcohol industry and environmental pollution surveillance.
      In carbohydrate structural chemistry, frequent use is made of formaldehyde by
      periodate oxidation of terminal vicinal diols. Popular methods for the detection
      of formaldehyde use reagents such as chromotropic acid (4,5-dihydroxynaphthalene
      2,7-disulfonic acid) or acetylacetone. The chromotropic acid method requires
      heating of the sample under strongly acidic conditions, which is undesirable in
      many applications. The acetylacetone method yields a yellow color product, and is
      less specific and sensitive (Mimura et al., J. Hyg. Chem. 22, 39-41, 1976). The
      reaction of formaldehyde with Purpald (4-amino-3-hydrazino-5-mercapto-1,2,4
      triazole) works under alkaline conditions at room temperature, and the
      sensitivity is superior to other methods. The color development by this reagent,
      however, requires oxidation of the adduct with hydrogen peroxide, air oxygen, or
      dilute periodate. We found that low levels of periodate, commonly used to oxidize
      specifically terminal vicinal diols to yield formaldehyde, are compatible with
      color development with the Purpald reagent. We have investigated the conditions
      required for use of the Purpald reagent, especially in conjunction with periodate
      oxidation reactions. We have used the assay either in test tubes or with
      microplates, attaining sensitivity of as little as 1 nmol formaldehyde.

PMID- 8742082
TI  - An in vitro test system for thyroid hormone action.
AB  - An in vitro bioassay for the biological action of thyroid hormones has been
      developed. The test is based on a dose-dependent increase in growth rate and cell
      activation of the rat pituitary tumor cell line GH3. This cell line is dependent
      on thyroid hormones for cell division when plated at low density in serum-free
      medium. The measurement of the cell-stimulating effect of L-triodothyronine (T3)
      is based on the capacity of mitochondrial enzymes of viable cells to transform
      the MTT tetrazolium salt into MTT formazan. A dose-dependent response of the MTT
      signal can be observed within a range from 0.075 to 1 nM T3 in the culture
      medium. The test is performed in 96-well microplates and allows screening of
      compounds which may interfere with the action of thyroid hormones.

PMID- 8742083
TI  - A nickel chelate microtiter plate assay for six histidine-containing proteins.
AB  - Protein purification has been made significantly easier by the use of affinity
      tags that can be genetically engineered at either the amino- or carboxyl-terminus
      of recombinant proteins. One of the most widely used tags is six consecutive
      histidine residues or 6His tag. These residues bind with high affinity to metal
      ions immobilized on chelating resins even in the presence of denaturing agents
      and can be mildly eluted with imidazole. We report the methodology for the
      immobilization of six histidine-containing proteins onto microtiter plates. A
      derivative of nitrilotriacetic acid (NTA) was prepared. This derivative, N,N
      bis[carboxymethyl]lysine (BCML), was easily coupled to a maleic anhydride
      activated polystyrene microtiter plate. The plate was then charged with Ni2+ for
      the capture of the 6His-tagged proteins. Using two different recombinant proteins
      with the 6His tag at either the N- or C-terminus, we demonstrated that the
      binding to the Ni(2+)-NTA plate was specific for six histidine-containing
      proteins. Proteins lacking the 6His tags did not bind to the plate. The plate was
      used in a modified enzyme-linked immunoabsorbent assay format to quantitate
      protein concentrations and determine the affinity of protein-ligand interactions.
      The technology can also be extended to include high-throughput screening assays
      for antagonists of protein-protein interactions.

PMID- 8742084
TI  - Evaluation of common electrophoretic methods in determining the molecular weight
      of apolipoprotein(a) polymorphs.
AB  - Five different gel systems were evaluated for their utility in determining the
      molecular weights of apolipoprotein(a) (apo(a)) polymorphs by SDS polyacrylamide
      or agarose gel electrophoresis. Three linear polyacrylamide gradient gels (2-16%
      from Isolab (Akron, OH), 4-15% from Pharmacia (Piscataway, NJ), and 2.5-6%
      homemade), a 4% polyacrylamide, and a 1.5% agarose gel were examined. Crosslinked
      phosphorylase B oligomers served as molecular weight standards. Molecular weights
      of four different apo(a) polymorphs were determined in each gel system and
      compared to values measured previously by sedimentation equilibrium. The results
      indicate that molecular weights obtained by gradient polyacrylamide gel
      electrophoresis were within 10% and often not statistically different from values
      acquired by sedimentation equilibrium. The use of homogenous 4% polyacrylamide
      and 1.5% agarose gels led to molecular weights that were overestimated by 20 and
      60-70%, respectively. ApoB100, which is a commonly used molecular weight marker,
      was found to have anomalously fast mobility in each of the four polyacrylamide
      gel systems. Because its use would lead to overestimated apo(a) molecular
      weights, it was not useful as a molecular weight standard. Our results indicate
      that SDS-gradient polyacrylamide gel electrophoresis with cross-linked
      phosphorylase B as standard is a suitable gel system for evaluating apo(a)
      molecular weights.

PMID- 8742085
TI  - A continuous microtiter plate assay for screening nucleotide sugar-synthesizing
      nucleotidyltransferases.
AB  - A continuous microtiter plate nucleotidyltransferase substrate screening assay
      (NUSSA) is described which allows the identification of nucleotide sugar
      synthesizing enzyme activities. The assay is accomplished by the determination of
      the common product of these enzymes PPi with a PPi-dependent phosphofructokinase.
      A subsequent enzyme reaction cascade leads to the production of 2 mol NAD per mol
      PPi. PPi-dependent phosphofructokinase was purified from potato with respect to
      contaminating enzyme activities which would disturb NUSSA performance. NUSSA
      allows the quick, simultaneous, and comprehensive check of different sugar 1
      phosphate and nucleoside triphosphate substrates using purified
      pyrophosphorylases or crude extracts of plants, microorganisms, and mammalian
      tissues. Moreover, NUSSA will assist to evaluate these enzymes for the synthesis
      of important nucleotide sugars which serve as substrates of glycosyltransferases
      in carbohydrate syntheses.

PMID- 8742086
TI  - Purification of single-stranded M13 DNA by cooperative triple-helix-mediated
      affinity capture.
AB  - A solid-phase triple-helix-mediated affinity capture method is described for the
      purification of single-stranded M13 DNA for use as template in fluorescence-based
      DNA sequencing reactions. In this method, a biotinylated polypyrimidine
      oligonucleotide "loop" bound to streptavidin-coated magnetic beads is used to
      selectively capture single-stranded M13 DNA from high-titer phage supernatant
      through the formation of a cooperative triple helix (CTH) complex between the
      oligonucleotide and a polypurine site previously cloned into the M13 vector.
      Capture is accomplished at acidic pH to encourage triple-helix formation, while
      elution is performed at alkaline pH with heating to destroy the CTH complex. The
      beads can be reused up to three times without probe replenishment. Yields of M13
      ssDNA in excess of 1 microgram per milliliter of culture are obtained, sufficient
      for use as template in fluorescence-based DNA sequencing reactions.

PMID- 8742087
TI  - No need of acetic acid for processing polyacrylamide gels.

PMID- 8742088
TI  - Determination of decarboxylase activity in adherent tissue culture cells.

PMID- 8742089
TI  - Application of Western blotting to the identification of metallothionein binding
      proteins.

PMID- 8742090
TI  - Western blot of proteins from Coomassie-stained polyacrylamide gels.

PMID- 8742091
TI  - Aphidicolin large-scale synchronization of rapidly dividing cell monolayers and
      the analysis of total histone and histone variant biosynthesis during the S and
      G2 phases of the HEp-2 cell cycle.

PMID- 8742092
TI  - Quantitation of hydrogen peroxide using tris(2-carboxyethyl)phosphine.

PMID- 8742093
TI  - Site-specific mutagenesis by using an accurate recombinant polymerase chain
      reaction method.

PMID- 8742094
TI  - Towards better pain treatment in cancer.
AB  - This review focuses on ways to ameliorate diagnosis and treatment of cancer
      related pain with currently available knowledge and methods. The first part
      indicates how to improve pain assessment and diagnosis in the cancer patient. The
      second part evaluates current views for adequate pain management based on
      evidence of double-blind analgesic trials in cancer-related pain and deals with
      misconceptions in established symptomatic therapy.

PMID- 8742095
TI  - Bicalutamide: a new antiandrogen for use in combination with castration for
      patients with advanced prostate cancer.
AB  - Maximum androgen blockade, a relatively recent development in the treatment of
      prostate cancer, combines medical or surgical castration with antiandrogen
      therapy. A large randomized study comparing the non-steroidal antiandrogen,
      bicalutamide, with flutamide, each in combination with luteinizing hormone
      releasing hormone (LHRH) analogs, showed that after a median follow-up of 49
      weeks, the time to treatment failure was significantly longer for the
      bicalutamide patients compared with the flutamide patients (p = 0.005). After a
      median follow up to 95 weeks, bicalutamide in combination with LHRH analog
      therapy produced at least equivalent efficacy with flutamide in combination with
      LHRH analog therapy in terms of time to treatment failure and equivalent efficacy
      in terms of survival. The tolerability profile of bicalutamide, as based on
      reported findings and a literature review, indicates a superior tolerability to
      that of currently available antiandrogens, particularly with respect to diarrhea
      with a low incidence of treatment-related withdrawals.

PMID- 8742096
TI  - Combining 5-fluorouracil with interferon-alpha in the treatment of advanced
      colorectal cancer: optimism followed by disappointment.
AB  - Pre-clinical data have demonstrated synergy between 5-fluorouracil (5-FU) and
      interferon (IFN)-alpha in colon cancer cell lines. In 1989 the first small single
      institution phase II study with this combination in advanced colorectal cancer
      showed a response of 81% with substantial toxicity, whereas IFN-alpha alone was
      virtually inactive. Ten published phase II studies including 175 evaluable
      patients have demonstrated a response rate of 2.3%. 5-FU alone has been used
      extensively and is moderately active with response rates of 10-11% in 1148
      patients evaluated by the Advanced Colorectal Cancer Meta-analysis Project in
      1992 and 1994. Eleven subsequent phase II studies with 5-FU + IFN-alpha published
      over the period of 1990-1994 on 548 patients showed a response rate of 28% with
      2% toxic deaths. Recently, nine phase III clinical trials including 1727
      randomized patients have compared 5-FU + IFN-alpha to some standard therapies,
      most often treatment regimens based on 5-FU + leucovorin. Except for one study
      involving 105 patients, the rest of the phase III studies have demonstrated
      either no difference (six studies) or significantly worse results (two studies
      showing substantial toxicity with IFN-alpha + 5-FU). Several studies are ongoing,
      but results are not likely to change. In conclusion, after a period of high
      hopes, the combination of 5-FU + IFN-alpha does not seem to fulfill the original
      expectations. It is costly, it is toxic and it is not effective. New treatment
      strategies must be developed if progress is to be obtained.

PMID- 8742097
TI  - Different doses of granulocyte colony stimulating factor to support a weekly
      chemotherapeutic regimen in advanced gastric cancer: a randomized study.
AB  - It was our intention to verify if increases of granulocyte colony stimulating
      factor (G-CSF) dose were able to reduce treatment delays due to leukopenia in our
      weekly regimen of cisplatin (40 mg/m2), epidoxorubicin (35 mg/m2), 6S-leucovorin
      (250 mg/m2) and 5-fluorouracil (500 mg/m2), usually supported by G-CSF at a dose
      of 5 mu g/kg. Forty five patients with advanced gastric carcinoma (30 males and
      15 females; median age 64 years) were randomized to receive three different doses
      of G-CSF (5, 8 and 10 mu g/kg) by s.c. injection. We did not observe any
      difference in the mean value of neutrophil counts at each of the 8 weeks of
      treatment; while we registered a higher incidence of severe neutropenia (<
      500/mm3) in patients receiving higher G-CSF doses: two patients in the group at 5
      mu g/kg, four in the group at 8 mu g/kg and seven in the group at 10 mu g/kg.
      Furthermore, low doses of G-CSF allowed a similar number of chemotherapeutic
      administrations in the eight study weeks. The results arising from our study do
      not seem to support the use of higher doses of G-CSF, at least in not such a
      weekly regimen.

PMID- 8742098
TI  - A phase II study of oral fluorouracil for gastrointestinal cancer.
AB  - Prolonged exposure to 5-fluorouracil (5-FU) is effective for gastrointestinal
      malignancy (GIM) and it is considered synergistic or additive to concurrent
      radiotherapy. Oral 5-FU (OF) could represent an easy therapy. The present study
      prospectively tested the toxicity and effectiveness of OF in GIM by means of 5-FU
      mannitol-coated tablets (MCT) at 275 or 225 mg/m2/day according to the patients
      age (65 years cut-off) for a period of 4 weeks every 7 weeks. Also the drug given
      over 5 days a week for 4 weeks was studied to assess OF toxicity over a time
      corresponding to that used in standard radiotherapy. Quality of life (LQ) was
      analyzed. Patients were 27 individuals (20 males), aged 43-70 years, pretreated
      with radiotherapy (four patients) or i.v. 5-FU-based chemotherapy (five
      patients), and with progressive malignancy of colorectum (six patients), stomach
      (five patients), pancreas (four patients) and liver (two patients). The total
      number of cycles was 91 and 16 patients had more than two cycles. Myelotoxicity
      was consistently absent; other toxicities greater than WHO grade 1 were: nausea
      (grade 2 in four patients), diarrhea (grade 2 in six and grade 3 in 11), palmar
      erithema (grade 2 in one), brown-turning skin (grade 2 in one) and CNS (grade 2
      in one). Diarrhea was less frequent (p = 0.007) in gastric and in colorectal than
      in pancreas and liver cancer patients. In the 10 patients given the drug of 5
      days a week, diarrhea was practically absent. LQ was above 90%. Fourteen patients
      (51%) had total arrest of disease, and 2 among 16 colorectal cancer patients had
      PR (12.5%). In conclusion, the MCT-OF was tolerated and as effective as the
      classic i.v. 5-FU at nonmyelosuppressive dose. The MCT-OF dose recommended for
      further studies is 275 mg/m2/day (or 225 above 65 years) for 4 weeks followed by
      a 2 week rest period.

PMID- 8742099
TI  - Absence of hepatic enzyme induction in prostate cancer patients receiving
      'Casodex' (bicalutamide).
AB  - The potential for hepatic enzyme induction by bicalutamide ('Casodex') was
      assessed in an open study in prostate cancer patients. A single, oral dose of
      antipyrine 1000 mg was given before and after 12 weeks' bicalutamide therapy
      [once daily 50 mg (n = 7) or 150 mg (n = 11)] and its pharmacokinetics and
      metabolism were determined. Plasma or saliva samples were taken for the
      measurement of antipyrine concentration. Urine samples were assayed for
      antipyrine and its three major metabolites. With bicalutamide 50 mg, plasma
      antipyrine concentrations were maximal between 2 and 4 h after administration,
      declined in a log-linear manner and were unaffected by bicalutamide therapy; with
      bicalutamide 150 mg, saliva antipyrine concentrations were maximal between 2 and
      4 h, declined in a log-linear manner, and were also unaffected by bicalutamide
      therapy. Antipyrine half-life was 16.3% shorter after bicalutamide 50 mg (p <
      0.05); a small decrease (13.5%) in half-life after bicalutamide 150 mg was not
      statistically significant. A small reduction (18.6%, p < 0.05) in the AUCinfinity
      for antipyrine was noted after bicalutamide 150 mg. A statistically significant
      reduction in antipyrine recovery was seen with the lower bicalutamide dose
      (23.7%, p < 0.05). The statistically significant changes were small in absolute
      terms and showed no dose-response relationship. Bicalutamide does not
      significantly induce the hepatic enzymes responsible for antipyrine metabolism
      and has no obvious potential for producing clinically significant drug
      interactions due to enzyme induction.

PMID- 8742100
TI  - Effect of modulators of the multidrug resistance pump on the distribution of
      vinblastine in tissues of the mouse.
AB  - Vinblastine at doses ranging from 0.2 to 6 mg/kg body weight was administered
      i.p. to mice in the absence or presence of the drugs PSC 833, cyclosporin A,
      mefloquine, quinidine and dipyridamole, all compounds that modulate the multidrug
      resistance pump and thus increase the accumulation of this cytotoxin in drug
      resistant cells in cell culture. In the absence of modulators, vinblastine
      accumulated in tissues to different extents--lowest in brain, highest in pancreas
      and intestine. The extent of accumulation was directly proportional to the
      vinblastine dose in the range 0.2-6 mg/kg body weight. Both at high and low
      vinblastine doses, all the modulators except quinidine increased the ability of
      liver, kidney, intestine and lung to accumulate vinblastine by up to 5-fold, and
      with the further exception of mefloquine, also increased vinblastine levels in
      pancreas. Only dipyridamole had a marked effect also in brain. Cyclosporin A
      provided effective increases in the tissue distribution of vinblastine at plasma
      concentrations similar to those needed to block the multidrug pump in the case of
      cells in cell culture. For mefloquine, plasma concentrations three or four times
      higher were needed in vivo than were found to be effective in cell culture. The
      mouse system provides a quick and reliable in vivo method to assay modulators
      before they are tested in the clinic.

PMID- 8742102
TI  - Tissue distribution, metabolism and excretion of paclitaxel in mice.
AB  - So far, all animal pharmacokinetic studies of paclitaxel, which used analytical
      procedures based on HPLC, have not been sensitive enough to quantify drug levels
      below 500 ng/ml. Consequently, the interpretation of the results is restricted
      because drug levels of paclitaxel as low as at least 50 nM (43 ng/ml) are
      relevant for the pharmacology of this drug. We recently described an accurate and
      very sensitive method based on HPLC for the determination of paclitaxel and the
      metabolites 3'-p-hydroxypaclitaxel (I), 6 alpha-hydroxypaclitaxel (II) and 6
      alpha,3'-p-dihydroxypaclitaxel (III) in a wide variety of biological matrices. We
      have now implemented this methodology in a comprehensive pharmacokinetic study in
      female FVB mice. Previous pharmacokinetic studies in humans demonstrated a large
      steady-state volume of distribution, indicating that the drug is widely
      distributed into tissues. Comprehensive tissue distribution studies may,
      therefore, be helpful in providing more insight into possible relationships
      between plasma levels, drug levels in tissues and toxicity. Paclitaxel,
      formulated in Cremophor EL and ethanol (1:1, v/v), was given as a single i.v.
      bolus dose of 2, 10 and 20 mg/kg to female FVB mice. Except for the brain, the
      distribution of paclitaxel to all other tissues in the female mice was
      substantial and maximum drug levels were achieved within 0.5 or 1 h. A marked non
      linear increase in the area under the concentration-time curve (AUC) in plasma
      was observed, which was not paralleled by a proportional increase in the tissue
      AUC levels. It is postulated that this effect may be related to the substantial
      amounts of Cremophor EL administered concurrently. The recovery of paclitaxel in
      the feces (0-96 h) was reduced from 58% at the 2 mg/kg dose level to 44% at the
      20 mg/kg dose level. Small amounts of metabolites I and II were detected in the
      gut, liver and gall bladder, but not in the systemic circulation or any other
      tissue. Metabolite III was not detected. Metabolites I and II are likely excreted
      directly into the bile, and since their recovery in the feces accounts for about
      25% of the administered dose, their formation thus represents an important
      pathway of detoxification.

PMID- 8742101
TI  - A topographic study on the distribution of cisplatin in xenografted tumors on
      nude mice.
AB  - The intratumoral distribution of cisplatin was studied in terms of platinum
      concentrations in tissue pieces and immunohistochemically detected cisplatin-DNA
      adducts in xenografted tumors on nude mice. Heterogeneities in drug distribution
      were calculated as standard deviations and coefficients of variation. A three
      dimensional image of adduct distribution was produced which showed regions with
      low adduct levels to be topographically connected also in three dimensions. A
      model was presented for investigating the potential influence of vascularization
      and cell proliferation on intratumoral adduct distribution by using different
      immunohistochemical stainings of parallel tissue sections. A weak but significant
      correlation was found between cisplatin-DNA adducts and proliferation, which
      might indicate that the drug uptake and adduct formation is increased in
      proliferating cells.

PMID- 8742103
TI  - The novel use of Rh(I) complexes with naphthyridine ligands and poly(oxyethylene)
      as antitumorals.
AB  - Rh(I) complexes adsorbed on polymers, as a way to improve their transport and
      solubility properties, were studied as antitumor agents. The binding constants of
      the complexes to the polymer were evaluated in order to determine the conditions
      for maximum association to the vehicle. The toxicity of the pure complexes and
      those bound were determined in vivo using female mice. [Rh(NBD)(2,4N)]CIO4,
      complex A; where NBD = norbornadiene, (2,4N) = 3,3'-dimethylene-2,2'-di-1,8
      naphthyridine, was investigated on primary solid tumors and ascitic tumors.
      [Rh(NBD)(3,4N)]CIO4, complex B; where (3,4N) = 3,3'-trimethylene-2,2'-di-1,8
      naphthyridine, was investigated on ascitic tumors. These Rh(I) complexes appear
      to be promising drugs because of their solubility in aqueous polymer, which make
      them easier to handle in comparison with the neutral species. These complexes
      show a similarity to cisplatin by reducing tumor growth and by increasing the
      survival life span of mice. Poly (oxyethylene) was used to solubilize these
      poorly water-soluble compounds and to stabilize the compounds in the solution
      before injection. These studies suggest that both complexes, A and B, are good
      candidates for tumor control growth and increase the survival time.

PMID- 8742104
TI  - Metabolism and action of benzamide riboside in Chinese hamster ovary cells.
AB  - Benzamide riboside (3-(1-deoxy-beta-D-ribofuranosyl)benzamide, BR) a new analog
      of nicotinamide riboside, is toxic to Chinese hamster ovary cells and inhibits
      guanine nucleotide synthesis in a manner comparable to that of tiazofurin (2-beta
      D-ribofuranosylthiazole-4-carboxamide). Adenosine kinase deficient cells
      demonstrate slight resistance but retain the ability to form the NAD analog,
      benzamide adenine dinucleotide (BAD). HPLC analysis of BAD containing cells is
      described. A BR resistant cell line was isolated that demonstrates cross
      resistance to both tiazofurin and 6-aminonicotinamide, suggesting a common
      metabolic step; enzymatic analysis indicates reduced levels of NAD
      pyrophosphorylase in these cells. BR toxicity was only partially reversed or
      prevented by the presence of guanosine, suggesting either that BR inhibits
      guanine salvage to some extent or, more probably, that BR can, at high
      concentration, inhibit cell growth by another mechanism in addition to inhibition
      of guanine nucleotide synthesis. Cells incubated with BR for several hours retain
      the ability to salvage exogenously provided guanosine. The demonstration that BAD
      can be phosphorylated by NAD kinase, presumably to form BADP, suggests that this
      metabolite may be formed in cells and may have inhibitory activity at high
      concentrations of BR.

PMID- 8742106
TI  - Correlation between sensitivity in vitro of patient chronic lymphocytic leukemia
      cells and clinical systemic exposure at the maximum tolerated dose for cell cycle
      phase-specific (type 2) anticancer drugs.
AB  - Previously in Anti-cancer Drugs we have reported a high correlation between
      clinical plasma concentration-time products (C x T) and the concentration of
      cytotoxic drugs giving 50% cell survival (IC50) in primary cultures of human
      lymphatic cells. In the present study we investigated the relationship separately
      for cell cycle-specific (type 1) and cell cycle non-specific (type 2) drugs in
      chronic lymphatic leukemia cells. A high correlation (R = 0.92) was observed
      between C x T and IC50 for cell cycle non-specific drugs, while for cell cycle
      specific, or C x T-dependent, drugs, the relationship was much weaker (R = 0.58).
      Since the opposite pattern has been observed for the relationship between
      clinical C x T and LD10 in mice, these results further imply that drug
      sensitivity assays may be a useful complement to animal data in the selection of
      starting dose and dose escalation procedure in phase I clinical trials of new
      cytotoxic drugs.

PMID- 8742105
TI  - Enhanced antitumor activity of an adriamycin + 5-fluorouracil combination when
      preceded by biochemical modulation.
AB  - A three-drug combination, PMA, consisting of (phosphonacetyl)-L-aspartic acid + 6
      methylmercaptopurine riboside + 5-aminonicotinamide, preceding either 5
      fluorouracil (5-FU) or adriamycin (Adr), produced tumor-regressing activity in a
      murine advanced breast tumor model not attainable with either 5-FU or Adr as
      single agents, or with any lesser combination of these drugs administered at
      maximally tolerated doses. Marked tumor-regressing activity was further increased
      significantly by using 5-FU and Adr together in conjunction with the modulatory
      biochemical conditioning (particularly ATP depletion) provided by pretreatment
      with PMA.

PMID- 8742107
TI  - Combination antiretroviral chemotherapy: a potential strategy in AIDS-related
      malignancy.
AB  - There has been considerable interest and controversy over the potential clinical
      role of combination antiretroviral therapy, primarily in the treatment of
      patients with established HIV infection. In order to model the hematologic
      toxicity of high-dose combination antiretroviral therapy, the HL60 myeloid
      leukemia cell line was exposed to zidovudine, dideoxycytidine and/or didanosine.
      The results suggest that the myelotoxicity of high-dose combination
      antiretroviral therapy may be controlled by using very brief periods of drug
      exposure. Brief intense antiretroviral therapy may offer a useful approach,
      particularly in the treatment of patients with AIDS-related neoplasms who are
      also receiving myelotoxic antineoplastic drugs.

PMID- 8742108
TI  - Therapeutic significance of the polyamine level in tissues of rats treated with
      adriamycin and cisplatin.
AB  - The effects of adriamycin (Adr) and cisplatin on body weight, organ weight, and
      the contents of putrescine, spermidine and spermine in 15 different tissues were
      examined in rats that had been given these drugs for 5 days. The weight of the
      spleen in cisplatin-treated rats, and of the thymus, spleen, kidney and heart in
      Adr-treated rats showed statistically significant decreases. Neither Adr nor
      cisplatin should be used to treat cancers in the seminal vesicle, and Adr should
      not be used to treat those in the large intestine due to significant increases in
      spermidine and spermine, which are associated with a risk of re-growth. However,
      Adr is recommended in the treatment of cancers in the thymus, kidney, skeletal
      muscle (femoral), heart, prostate, testis, liver, small intestine and lung, based
      on decreases in some of the polyamines, while cisplatin is not recommended in the
      thymus, kidney, skeletal muscle or heart for the same reason that Adr is not
      recommended to treat cancers of the large intestine (rectum). The ratio of
      spermidine to spermine was significantly higher in the skeletal muscle of
      cisplatin-treated rats and in the small intestine and brain of Adr-treated rats,
      and was lower in the prostate, seminal vesicle and spleen of Adr-treated rats
      than in control rats.

PMID- 8742109
TI  - Administration of Ethyol (amifostine) to a child with medulloblastoma to
      ameliorate hematological toxicity of high dose carboplatin.
AB  - The first report on the administration of the chemoprotective agent Ethyol
      (amifostine) in conjunction with high dose carboplatin to a patient in the
      pediatric/adolescent age group is presented. A 17 year old teenager with
      recurrent cerebellar medulloblastoma received a total of five courses of high
      dose carboplatin 2 x 600 mg/m2 (1200 mg/m2 total) in each cycle. A complete
      response has been observed following the third treatment cycle. However,
      cumulative grade IV hematological toxicity developed following each of the first
      four treatments. Therefore, the fifth treatment was administered in conjunction
      with amifostine, at a dose of 2 x 740 mg/m2. Time to complete hematological
      recovery (Hb > 100 g/l, granulocytes > 2.0 G/l, platelets > 100 G/l) was 52, 58,
      72, 78 and 50 days, respectively, following treatments nos 1, 2,,3, 4 and 5. The
      duration of grade III-IV neutropenia (< 1.0 G/l) was 3, 7, 8, 10 and 5 days,
      respectively. The duration of grade II-IV thrombocytopenia (platelets < 75 G/l)
      was 10, 25, 35, 40 and 32 days, respectively. Grade IV thrombocytopenia
      (platelets < 25 G/l) lasted for 5, 10, 12, 18 and 3 days, respectively, after
      each consecutive treatment. The total number of platelet transfusions was 1, 2,
      2, 3 and 1, with the transfusion of 6, 9, 11, 11 and 5 units of platelets. The
      administration of amifostine has not been accompanied by any serious side effect.
      A short decrease in body temperature and a transient drop of blood pressure have
      been observed. Although hematological toxicity of high dose carboplatin has not
      been eliminated by amifostine, we conclude that significant protection was
      achieved in this situation of progressive bone marrow exhaustion.

PMID- 8742110
TI  - Re: 'Cost-effectiveness of 5-hydroxytryptamin3 receptor antagonists: a
      retrospective comparison of ondansetron and granisetron'.

PMID- 8742111
TI  - Third European workshop on drug information, Helsinki, Finland, 14-16 June 1995.

PMID- 8742112
TI  - Effects of growth hormone on cerebral development: morphological studies.
AB  - Growth hormone (GH)-deficient mice exhibit a microcephalic cerebrum with
      hypomyelination, retarded neuronal growth with poor synaptogenesis, and reduced
      levels of spontaneous locomotion activity with an indistinct diurnal periodicity.
      The hypomyelination is found to be due to arrested glial proliferation,
      suggesting that the action of GH on the proliferation and maturation of both
      glial and neuronal cells is a necessary precondition of myelin formation, apart
      from the complementary or synergistic actions of T4. In contrast, the cerebral
      hypomyelination in hypothyroid mice is not related to arrested glial
      proliferation, demonstrating that thyroid hormones can act independently on
      myelinogenesis. On the other hand, the activity of sn-glycerol-3-phosphate
      dehydrogenase is significantly depressed in hypothyroid cerebella, suggesting
      that T4 is indistinguishable for the maturation of Bergmann glial cells. In
      addition, the developmental expression of hippocalcin in the GH-deficient brain
      is retarded, suggesting the poor maturation of the neuronal network, because
      hippocalcin is considered to associate in postsynaptic neural functions and in
      synaptic plasticity.

PMID- 8742113
TI  - Growth hormone and its receptors in the central nervous system--location and
      functional significance.
AB  - During the past few years, there has been increasing interest in functions that
      growth hormone (GH) may play in the central nervous system. Accumulating evidence
      that the hormone may pass the blood-brain barrier and the psychological
      improvements seen in adults following GH therapy have received particular
      attention. This paper will review our recent studies on GH receptors in the human
      and rat brain. A recent study on the effects of GH treatment in adult growth
      hormone-deficient patients on quality of life and cerebrospinal fluid levels of
      various hormones and neurotransmitters is also included.

PMID- 8742114
TI  - Growth, growth hormone and cognitive functions.
AB  - The interactions among short stature, growth hormone (GH) and cognitive functions
      have been extensively studied so far. However, although it seems well established
      that short stature is associated with cognitive problems, little effort has been
      made to point out the presence of specific psychological effects related to the
      different forms of short stature. In 'short normal' children, the presence of a
      scholastic underachievement seems to suggest that short stature 'itself' might
      predispose these patients to some of their psychosocial difficulties. The higher
      incidence of academic failure, in presence of a normal intellectual functioning,
      has been attributed to environmental and psychosocial factors, including over
      protective parents and low self-esteem resulting from the impact of short
      stature. These problems appear to be common also to other forms of short stature
      (such as Turner's syndrome) where, however, they are frequently associated with
      other specific deficits. The in vivo model which might allow, at least in part,
      better understanding of GH (per se)-dependent effects is represented by GH
      deficiency (GHD), in which, however, the specific role of GH on psychological
      functioning is frequently masked by the presence of associated hormonal
      deficiencies. Children with isolated GHD are reported to have specific
      educational deficits, in particular learning disability and attention-deficit
      disorders, which have been tentatively attributed to a compromised intellectual
      potential. The psychological effects of long-term GH treatment in children with
      GHD still remain controversial, with some retrospective studies describing a
      generally beneficial outcome. Since early experiences in school are closely
      related to success in adult life, the possible implications that GHD during
      childhood holds during adulthood have been recently considered. Although regional
      differences have been observed in subgroups of adults with GHD, it seems that
      these patients have normal cognitive functions and educational attainment, but
      are more likely to be unemployed (and unmarried) than members of the general
      population. In general, patients with GHD, who have been treated at centers where
      psychological counselling was an integral part of the treatment program, seem to
      be better adjusted in adult life. For these reasons, a multidisciplinary
      treatment approach could allow early detection of problems in academic
      achievement and psychosocial development in patients with short stature, being
      immediately able to provide the appropriate educational and counselling
      interventions.

PMID- 8742115
TI  - Links between growth hormone deficiency, adaptation and social phobia.
AB  - Children referred for growth hormone (GH) treatment have increased school
      achievement problems, lack appropriate social skills and show several forms of
      behavior problems. A multicenter study in the United States has revealed that
      many GH-impaired children exhibit a cluster of behavioral symptoms involving
      disorders of mood and attention. Anxiety, depression, somatic complaints and
      attention deficits have been identified. These symptoms decline in frequency over
      a period of 3 years, beginning shortly after GH replacement therapy is started.
      Many of the patients who have received GH and had good growth responses show
      lower than average quality of life in young adulthood after treatment is
      completed. GH-deficient adults placed on GH therapy report improvement in
      psychological well-being and health status, suggesting that GH might have a
      central neuroendocrine action. Among a group of adults who were GH deficient as
      children, we find a high incidence of social phobia, a psychiatric disorder
      linked to GH secretion and usually accompanied by poor life quality. An ongoing
      study of non-GH-deficient short individuals suggests that short stature is not
      the cause of this outcome. We conclude that the origins of psychiatric
      comorbidities, such as social phobia and depression, in GH deficient adults are
      likely to be neuroendocrine as well as psychosocial.

PMID- 8742116
TI  - Growth hormone deficiency and quality of life.
AB  - Quality of life research in adults with growth hormone deficiency (GHD) is a
      developing field. It has been recognised that adults with childhood onset GHD
      suffer social and psychological disadvantages. The effects of GHD of adult onset
      have only been shown relatively recently. Assessment of these patients, using
      measures of physical and psychological well-being, has demonstrated that adults
      with GHD perceive themselves as much less healthy compared with matched controls.
      The majority of studies investigating the effects of growth hormone replacement
      therapy indicate that quality of life improves with treatment, although this is
      not a consistent finding.

PMID- 8742117
TI  - Growth hormone, growth factors and hematopoiesis.
AB  - Hypocellularity of primary lymphoid organs is a distinctive and reproducible
      characteristic of aged humans and animals. Similar changes have been reported in
      both hypophysectomized and dwarf rodents. In the bone marrow of these animals,
      there is an associated reduction in the number of erythroid, lymphoid and myeloid
      elements. Implantation of growth hormone (GH)-secreting GH3 pituitary cells or
      infusion of growth hormone into aged rodents dramatically improves cellularity of
      both the thymus gland and bone marrow. At present it is unknown whether these
      effects are due to direct effects of growth hormone on hematopoietic cells or if
      they are caused by the induction of insulin-like growth factor-1 (IGF-1)
      synthesis. We recently discovered that colony-stimulating factor-1 (CSF-1) and
      interleukin-3 (IL-3) induce expression and synthesis of the IGF-1 peptide in
      murine bone marrow cells. Transcripts for IGF-1 increase approximately 50-fold
      during differentiation over the negligible levels that are expressed in freshly
      isolated bone marrow cells. Two potential functions of macrophage-derived IGF-1
      are to: (a) increase the proliferation of early or committed bone marrow
      progenitors and (b) reduce their rate of cell death. In support of the first
      possibility, IGF binding protein-3 significantly inhibits the proliferation of
      CSF-1-treated bone marrow cells and this inhibition can be reversed by addition
      of exogenous IGF-1. In support of the second possibility, we have induced
      apoptosis of both nonadherent bone marrow cells and a myeloid progenitor cell
      line by depriving these cells of CSFs. Preliminary results indicate that addition
      of IGF-1 to these cells reduces apoptotic cell death by 50%. These data establish
      that two different CSFs, CSF-1 and IL-3, induce abundant expression of IGF-1 as
      these cells differentiate into more mature hematopoietic cells. This model offers
      a novel approach for investigating the developmental expression of IGF-1 during
      defined differentiation pathways of hematopoietic cells. If IGF-1 is indeed
      proven to act as a survival factor for hematopoietic progenitors, these data
      would support the idea that the hypocellularity of primary lymphoid tissues in
      aged animals is related to the limited availability to these cells of either
      growth hormone or IGF-1.

PMID- 8742118
TI  - Aging and immune function: a possible role for growth hormone.
AB  - Elderly individuals have four to five times the case rate of cancer, tuberculosis
      and herpes zoster and six to seven times the fatality rate from pneumonia
      compared to young adults. This may be causally related to two changes that occur
      with aging, i.e. decreased growth hormone (GH)/insulin-like growth factor-1 (IGF
      1) production and decreased immune function. Data from our laboratory as well as
      others have shown that, based on either GH secretory dynamics or IGF-1 levels,
      approximately 40% of adults aged 60 and older are GH deficient. In the same
      population of subjects, immune function decreases such that there is a decline in
      cell-mediated and humoral immune responsiveness. Some of these immune deficits
      have been shown to be reversed in humans and primates by GH and/or IGF-1
      treatment. This paper will review some of these data.

PMID- 8742119
TI  - Growth hormone and the immune response to bacterial infection.
AB  - Growth hormone (GH) and insulin-like growth factor 1 (IGF-1), especially the
      former, have immunoregulatory effects in addition to anabolic effects. The
      hormones may act to protect the host from lethal bacterial infection by promoting
      the maturation of myeloid cells, stimulating phagocyte migration, priming
      phagocytes for the production of superoxide anions and cytokines, and enhancing
      opsonic activity. GH administration may be beneficial for the prevention, as well
      as treatment, of severe sepsis in critical illness.

PMID- 8742120
TI  - Effects of human growth hormone on the catabolic state after surgical trauma.
AB  - The aims of our studies were: (1) to determine if the protein catabolic response
      after a major or moderate surgical trauma can be restrained by the administration
      of exogenous human growth hormone (hGH); (2) to determine if the administration
      of hGH can improve systemic host defenses, thus reducing the risk of infection,
      and (3) given that the postoperative fatigue syndrome (POF) is mediated by the
      endocrino-metabolic response to surgery we attempt to determine if the
      administration of hGH can prevent or reduce POF. Therefore, we performed three
      placebo-controlled randomized double-blind trials on 216 patients. Major
      gastrointestinal surgery was treated only with total parenteral nutrition (TPN; n
      = 20) or TPN plus 4 IU hGH (n = 18). Patients with moderate surgical trauma
      received either hypocaloric parenteral nutrition (HPN; n = 93) or HPN and 8 IU
      hGH (n = 87). In this study, we also determined the evolution of the systemic
      host defenses and thereby the risk of infection. In 48 patients who underwent
      cholecystectomy treated (n = 26) either with HPN or HPN plus 8 IU hGH, we
      measured the protein catabolic response, postoperative fatigue and anthropometric
      modifications. The treatment with hGH together with HPN or TPN (1) overcomes the
      protein catabolic effects of the trauma response induced by major or moderate
      surgery by increasing protein synthesis, (2) improves humoral and cellular
      systemic host defenses, thus reducing the risk of infection, (3) preserves or
      increases lean body mass and reduces adipose tissue and (4) minimizes POF.

PMID- 8742121
TI  - The ontogeny of growth hormone, insulin-like growth factors and sex steroids:
      molecular aspects.
AB  - Insulin-like growth factors (IGF-1 and IGF-2) are synthesized by many tissues in
      response to GH treatment and regulate cellular growth and differentiation. Fetal
      serum contains abundant GH, and many fetal tissues express GH receptors, but the
      clinical significance of GH in fetal development in humans is uncertain because
      hypopituitary newborns have normal birth size. The biological actions of IGFs are
      modulated by a family of binding proteins (IGFBPs). The demonstration of IGF and
      IGFBP transcripts in preimplantation embryos indicates that the influence of IGFs
      and IGFBPs in fetal development begins even prior to implantation. IGF and IGFBP
      mRNAs, except IGFBP-1 mRNA, are expressed at variable levels in many fetal
      tissues throughout gestation. Although the IGF mRNAs are widely expressed, IGFBP
      mRNAs manifest in specific cell types in a spatially and temporally specific
      manner, suggesting that they indicate sites of IGF action. Conditions of
      undernutrition and chronic hypoxemia, known to cause intrauterine growth
      retardation in fetuses, alter IGFBP and IGF-1 but not IGF-2 gene expression, thus
      indicating the role for IGF-1 and IGFBPs as mediators of altered growth. IGF and
      IGFBP genes are also expressed in many fetal endocrine tissues including those
      secreting sex steroids. Null mutation of the IGF-1 gene leads to retarded
      development of the primary sex organs. In the fetal adrenal gland, IGF-2 mRNA is
      localized to 3 beta-hydroxysteroid hydrogenase (3 beta-HSD) immunoreactive cells,
      suggesting a close relationship to steroid hormone biosynthesis. IGFBPs are
      important paracrine modulators of IGF action during development, and are crucial
      regulators of cellular growth and differentiation by modulating IGF-dependent or 
      independent actions in all tissues including developing endocrine glands.

PMID- 8742122
TI  - Sex steroid regulation of growth hormone secretion and action.
AB  - Evidence that oestrogen is involved in the regulation of the somatotrophic axis
      in adult humans is provided by the observations that mean growth hormone (GH)
      levels are higher in women than men, that the fall in GH and insulin-like growth
      factor-1 (IGF-1) with aging are correlated to oestradiol levels and that
      oestrogen increases the GH responses to provocative stimuli. To investigate
      whether oestrogen modulates GH secretion and action in adult life, we studied the
      impact of oestrogen replacement on circulating GH and IGF-1 levels in
      postmenopausal women. Since the liver is the major source of circulating IGF-1
      and the oral route of oestrogen delivery causes nonphysiologic effects on hepatic
      proteins, we compared the effects of oral and transdermal routes of delivery.
      Oral ethinyl oestradiol administration resulted in a significant fall in mean IGF
      1 levels and a threefold increase in mean 24-hour GH. Transdermal administration
      of 17 beta-oestradiol resulted in a slight increase in serum IGF-1 but no change
      in mean 24-hour GH levels. To determine whether differences in oestrogen type
      rather than in the route of delivery caused the different effects on the GH/IGF-1
      axis, we compared the effects of three oral oestrogen formulations. Ethinyl
      oestradiol, conjugated equine oestrogen and oestradiol valerate each induced a
      fall in IGF-1 and a rise in mean 24-hour GH levels in postmenopausal women. To
      determine the significance of oestrogen-induced changes on IGF-1, we studied
      effects on markers of connective and bone tissue activity. We found that
      propeptide concentrations of type III and type I collagen, and osteocalcin rose
      and fell in parallel with IGF-1 during oral or transdermal oestrogen therapy.
      Oestrogen causes distinct, route-dependent effects on the somatotrophic axis. The
      dissociation of the GH/IGF-1 axis by the oral route is likely to arise from
      impaired hepatic IGF-1 production which causes increased GH secretion through
      reduced feedback inhibition. Oestrogen treatment may have longer-term metabolic
      effects on hypogonadal women exerted through effects on the somatotrophic axis.

PMID- 8742123
TI  - Sex steroids, growth hormone, insulin-like growth factor-1: neuroendocrine and
      metabolic regulation in puberty.
AB  - The control of the onset of puberty involves the complex interaction of pituitary
      and gonadal hormones. At a preprogrammed time in a child's life there is an
      increase in the amplitude of GnRH pulses which triggers a cascade of events
      including increases in the amplitude of FSH and LH pulses, followed by marked
      increases in gonadal sex steroidal output, which in turn increases growth hormone
      (GH) and insulin-like growth factor-1 (IGF-1) production. Evidence suggests that
      there is an integral interaction between the endogenous opiate system and the
      hypothalamic-pituitary-gonadal axis, at least in the later stages of puberty in
      the male. Both androgenic and estrogenic hormones markedly increase GH production
      rates as measured by deconvolution models in the prepubertal human, and
      compelling data strongly suggest that it is indeed the estrogen which controls
      the feedback amplification of GH production during puberty even in the male. It
      appears that the prepubertal gonad is actively producing sex hormones which might
      be important in the control of GH production since early childhood. The
      translation of these neuroendocrine rhythms into distal metabolic actions is also
      reviewed. Utilizing isotopic tracer infusions of the essential amino acid
      leucine, studies clearly show a selective stimulation of whole body protein
      synthesis by both GH and IGF-1. GH, IGF-1 and androgenic hormones all increase in
      puberty, stimulating whole body protein anabolism during that period. However, we
      observed no protein-anabolic effect in the hypogonadal female given increasing
      doses of estrogen. The latter suggests that at least as it pertains to whole body
      protein effects, the action of androgens is probably mediated via the androgen
      and not the estrogen receptor, in clear distinction from the estrogen-mediated
      effects of androgens on the neuroendocrine axis. Calcium absorption and retention
      are also positively affected by the androgens as shown by significant increases
      in calcium absorption and retention after the administration of testosterone to
      the prepubertal male. This suggests an important role of sex steroidal hormones
      in the mineralization of the skeleton. IN CONCLUSION: GH, IGF-1 and sex steroids
      all markedly increase during puberty and their actions are amplified mutually as
      they control growth, increase muscle mass and affect the mineralization of the
      skeleton. The dichotomy of androgen and estrogen effects in the male and female
      may regulate the differential timing of the onset of puberty and final height in
      the two sexes. The synergistic actions of these anabolic hormones appear to be
      most significant during the finite years of puberty.

PMID- 8742124
TI  - Growth hormone and fertility--clinical studies.
AB  - The linkage between the reproductive and somatotropic axes and the existence of a
      complex regulating system within the ovary involving growth factors and their
      binding proteins suggest that the ovary may be a target of growth hormone (GH)
      action. Clinical studies investigating possible applications of adjuvant GH
      treatment in ovulation induction and in vitro fertilization, mainly directed at
      poor responders to gonadotropin therapy, have shown that results are dependent on
      the hormonal status and 'ovarian age' of the subject. Additive GH is capable of
      increasing the sensitivity of ovaries to gonadotropins in those with a blatant or
      subtile lack of GH but not in those with a normal, saturated system. Improved
      pregnancy rates have not been convincingly forthcoming and more research is
      needed on the effect of GH and growth factors on the oocyte and endometrium.
      Disturbed GH kinetics in the polycystic ovary syndrome have prompted
      investigations of possible involvement of GH in the pathophysiology of this
      syndrome.

PMID- 8742125
TI  - Role of growth hormone and sex steroids in achieving and maintaining normal bone
      mass.
AB  - It is now established that adults with growth hormone (GH) deficiency, of
      childhood or adult onset, have reduced bone mass. GH deficiency is believed to
      interfere with acquisition of bone mass, although an alternative mechanism is
      required to explain the reduction in bone mass present in adults who acquire GH
      deficiency after peak bone mass has been achieved. GH replacement increases bone
      turnover and may increase bone mass in the longer term, although short-term
      studies show a decrease in bone mass which can be explained by an increase in
      bone resorption before new bone formation occurs. Abnormalities of GH secretion
      have also been implicated in the development of osteoporosis, but the effect of
      GH treatment on bone mass in such patients is disappointing. Sex steroids have an
      important role to play in the acquisition of bone mass, and reduced sex steroid
      levels during adolescence have a deleterious effect on bone mass. The importance
      of sex steroids in the maintenance of bone mass is illustrated by the development
      of osteopenia in men and women with hypogonadism, and by the preservation of bone
      mass by restoration of normal endogenous sex steroid levels, or by treatment with
      exogenous sex steroid. Sex steroids also influence circulating levels of GH and
      insulin-like growth factor-1, and the inter-action between these hormones is
      likely to be important in the acquisition and maintenance of normal bone mass.

PMID- 8742126
TI  - Influence of growth hormone and androgens on body composition in adults.
AB  - The secretion of both growth hormone (GH) and androgens declines with age which
      may play a role in the senescent changes in body composition and organ function.
      Among healthy adults abdominal adiposity is an important negative determinant of
      GH secretion. Surprisingly, abdominal or android obesity seems inversely
      correlated with testosterone levels in males but not in females. The ability of
      GH to promote lipolysis and preserve or increase lean body mass has been
      reappraised in substitution studies in GH-deficient adults. By comparison,
      adequately controlled studies of androgen replacement in hypogonadal and/or
      elderly males are few. In view of the physiological and clinical relevance of
      obtaining information about the aging process, there is a need for controlled
      experiments addressing similarities and differences between the action of GH and
      sex steroids in adults.

PMID- 8742127
TI  - Growth hormone axis in cushing's syndrome.
AB  - All levels of the growth hormone (GH), GH binding protein (GHBP), insulin-like
      growth factor (IGF) and IGF binding protein (IGFBP) axis are influenced by
      chronic hypercortisolism. Thus, there is a blunted response to GHRH alone or
      together with other stimuli associated with a marked suppression of endogenous GH
      secretion but accompanied by normal GHBP, normal to low IGF-1 and GHBPs 1 and 3
      with the correspondent 41.5 and 38.5-kD molecular forms of the latter presenting
      values similar to normal. These findings may suggest enhanced GH sensitivity with
      normal or increased IGF-1 bioavailability to the correspondent tissue receptors.
      In conclusion, the glucocorticoid (GC)-induced target tissue resistance can
      neither be attributed to the suppression of the GH axis nor to changes in
      circulating GHBPs 1 and 3. However, it may be related either to the described 12
      to-20-kD inhibitor(s) which antagonizes postbinding IGF-1 bioactivity (gene
      expression) and/or by the downmodulation of activator protein-1 (Fos/Jun)
      activity by the GC-GC receptor complex.

PMID- 8742128
TI  - Mutations of the fibroblast growth factor receptor-3 gene in achondroplasia.
AB  - Achondroplasia (ACH), the most common cause of chondrodysplasia in man (1 in
      15,000 live births), is an autosomal dominant condition of unknown origin
      characterized by short-limbed dwarfism and macrocephaly. Recently, a gene for ACH
      has been mapped to chromosome 4p16.3. The genetic interval encompassing the
      disease gene contains a member of the fibroblast growth factor receptor (FGFR)
      family which is expressed in articular chondrocytes (FGFR3). We report here
      recurrent missense mutations, in a CpG doublet of the transmembrane domain of the
      FGFR3 protein (G380R) in 17 sporadic cases and 6 unrelated familial forms of ACH
      and show that the mutant genotype segregates with the disease in these families.
      Thus, it appears that recurrent mutations of a single amino acid in the
      transmembrane domain of the FGFR3 protein account for all cases (23/23) of
      achondroplasia in our series.

PMID- 8742129
TI  - Analysis of TGF-beta 1 gene expression in contused rat spinal cord using
      quantitative RT-PCR.
AB  - We have used northern blot analysis and quantitative reverse transcription
      polymerase chain reaction (RT-PCR) to determine the postinjury expression profile
      of the transforming growth factor-beta 1 (TGF-beta 1) gene in the contused rat
      spinal cord. Spectrophotometric estimates of total sample RNA and quantitative
      analyses of cyclophilin mRNA using RT-PCR served as controls for comparisons
      between samples. No changes in cyclophilin gene expression were found at any
      postinjury survival times. The results of the TGF-beta 1 analyses, which were
      carried out on spinal cord samples taken at postinjury intervals ranging from 6 h
      to 10 days, show that the amount of TGF-beta 1 mRNA present in spinal cord
      increases rapidly following injury, reaching maximum levels 7 days postinjury.
      Unoperated control samples contained approximately 2 x 10(8) molecules of TGF
      beta 1 mRNA/0.5 microgram total RNA. By 1 day postinjury, the amount of TGF-beta
      1 mRNA in the cord had increased by a factor of 2.5 to 5 x 10(8) molecules/0.5
      microgram total RNA. At 7 days postinjury, there were approximately 15 x 10(8)
      molecules of TGF-beta 1 mRNA/0.5 microgram total RNA. By 10 days postinjury the
      amount of TGF-beta 1 mRNA present in the spinal cord had declined to 8 x 10(8)
      molecules of TGF-beta 1 mRNA/0.5 microgram total RNA, a value similar to that
      observed at 3 days postinjury. The roles that TGF-beta 1 might play in modifying
      cellular responses in injured spinal cord are discussed.

PMID- 8742130
TI  - Severe controlled cortical impact in rats: assessment of cerebral edema, blood
      flow, and contusion volume.
AB  - Controlled cortical impact (CCI) is a contemporary model of experimental cerebral
      contusion. We examined the cerebrovascular and neuropathologic effects of a
      severe CCI in rats. The utility of magnetic resonance imaging (MRI) for the
      assessment of contusion volume after severe CCI was also established. Severe CCI
      (3.0 mm depth, 4 m/sec velocity) to the left (L) parietal cortex was produced in
      anesthetized (isoflurane/N2O/O2), intubated, and mechanically ventilated male
      Sprague-Dawley rats (n = 58). Physiologic parameters were controlled. The time
      course of alterations in edema [L-R% brain water (% BW) in 3-mm coronal sections
      through injured and contralateral hemispheres, wet-dry weight] was evaluated at 2
      h, 24 h, 48 h, and 7 days posttrauma. Local cerebral blood flow (ICBF, measured
      in 8 structures in each hemisphere by autoradiography) was evaluated at 2 h, 24
      h, and 7 days. Contusion volume (measured by histology and image analysis) was
      assessed at 14 days and measured in 6 rats by both MRI and histology. The
      survival rate after severe CCI was 96.2%. The L-R difference in % BW increased to
      1.69 +/- 0.18% at 2 h, 3.00 +/- 0.08% at 24 h, 2.69 +/- 0.09% at 48 h, and 0.94
      +/- 0.21% at 7 days. These values all differed from the control (p < 0.05). The %
      BW was greater at 24 h and 48 h than at 2 h and 7 days (p < 0.05). Marked
      reductions in ICBF were limited to structures in the injured hemisphere and were
      observed in the parietal cortex (2 and 24 h), subcortical white matter (2 and 24
      h), and hippocampus (2 h), (p < 0.05) vs control rats. In the contusion core,
      ICBF was 19.4 +/- 8.8 mL 100 g-1 min-1 at 24 h (p = 0.011 vs normal). Necrosis
      was seen in large portions of the parietal cortex and subcortical white matter,
      and portions of the hippocampus and thalamus. Contusion volume was 47.8 +/- 9.2
      mm3, which represented 14.4 +/- 2.1% of the traumatized hemisphere. Estimates of
      contusion volume by MRI and histology were closely correlated (r = 0.941, p <
      0.017). Severe CCI in rats is accompanied by contusion, reproducible edema, and
      marked hypoperfusion, involving over 14% of the injured hemisphere, and can be
      produced with minimal mortality. T2-weighted MRI successfully and noninvasively
      identifies contusion volume in this model.

PMID- 8742131
TI  - Impact acceleration-induced severe diffuse axonal injury in rats:
      characterization of phosphate metabolism and neurologic outcome.
AB  - Diffuse axonal injury (DAI) occurs in over half of all severe cases of traumatic
      brain injury and has been associated with the development of a persistent
      vegetative state. Although a number of studies have examined the biochemical and
      physiological events following brain trauma, none of these has concentrated on
      events associated with the occurrence of severe DAI. The present study has used
      phosphorus magnetic resonance spectroscopy (MRS) and the rotarod motor test to
      characterize metabolic and neurologic consequences of severe diffuse axonal
      injury in rats induced by impact acceleration. Traumatic brain injury was induced
      in male rats by dropping a 450-g brass weight a distance of 2 m onto a 10-mm
      stainless-steel disc (3 mm wide) attached to the closed skull. Changes in brain
      intracellular pH, free magnesium concentration, cytosolic phosphorylation ratio,
      and mitochondrial oxidative metabolism after injury were monitored by phosphorus
      MRS while neurologic motor outcome over 1 week was assessed using the rotarod
      test. Impact acceleration-induced injury resulted in a highly significant decline
      in free magnesium concentration, cytosolic phosphorylation ratio, and an
      increased rate of mitochondrial oxidative phosphorylation, but no significant
      change in pH. These changes were associated with the occurrence of a significant
      neurologic deficit over 1 week postinjury. The similarity in metabolic events
      associated with production of neurologic deficits in this and other models of
      traumatic brain injury suggests that these bioenergetic changes may be common to
      all models of brain trauma.

PMID- 8742132
TI  - Regional concentrations of cyclic nucleotides after experimental brain injury.
AB  - Regional concentrations of lactate, glucose, cAMP, and cGMP were measured after
      lateral fluid percussion brain injury in rats. At 5 min after injury, while
      tissue concentrations of lactate were elevated in the cortices and hippocampi of
      both the ipsilateral and contralateral hemispheres, those of glucose were
      decreased in these brain regions. By 20 min after injury, increases of lactate
      concentrations and decreases of glucose concentrations were observed only in the
      cortices and in the hippocampus of the ipsilateral hemisphere. Whereas the cAMP
      concentrations were unchanged in the cortices and hippocampi of the ipsilateral
      and contralateral hemispheres at 5 min after injury, decreases were found in the
      injured cortex and ipsilateral hippocampus at 20 min after injury. The tissue
      concentrations of cGMP were found to be elevated only in the ipsilateral
      hippocampus at 5 min after injury. The present observation that tissue glucose
      decreases in the injured cortex and the ipsilateral hippocampus are consistent
      with the published findings of increased hyperglycolysis and oxidative metabolism
      in brain immediately after injury. The present findings that the concentrations
      of cAMP and cGMP change in the cortex and hippocampus provide biochemical
      evidence for the neurotransmitter's surge after brain injury.

PMID- 8742133
TI  - Differential consequences of lateral and central fluid percussion brain injury on
      receptor coupling in rat hippocampus.
AB  - We have identified alterations in the responses of muscarinic and metabotropic
      receptors in rat hippocampus that persist for at least 15 days after central
      fluid percussion injury. This study compares the effect of lateral fluid
      percussion and central fluid percussion on these responses. Moderate injury was
      obtained by displacement and deformation of the brain within the closed cranial
      cavity using a fluid percussion device positioned either centrally or laterally.
      Carbachol and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD)
      stimulated polyphosphoinositide (PPI) hydrolysis was assayed in hippocampus from
      injured and sham-injured controls at 15 days following injury. At 15 days after
      central fluid percussion traumatic brain injury (TBI), the response to carbachol
      was enhanced by 30% and the response to trans-ACPD was enhanced by 75% compared
      to sham-injured animals. At 15 days after lateral fluid percussion TBI the
      response to trans-ACPD was enhanced by 40% both ipsilateral and contralateral to
      the side of injury. In contrast, the response to carbachol was enhanced by 29%
      contralateral to the side of injury but was diminished by 12% ipsilateral to the
      side of injury. Cresyl violet staining shows no hippocampal cell death after
      central fluid percussion injury or on the side contralateral to lateral fluid
      percussion injury but on the ipsilateral side cell death was identified in
      hippocampal area CA3. Thus, abnormal hippocampal cell signaling through the
      phosphoinositide pathway occurs in the absence of cell death and may contribute
      to cognitive impairment.

PMID- 8742134
TI  - Fetal hippocampal transplants attenuate CA3 pyramidal cell death resulting from
      fluid percussion brain injury in the rat.
AB  - Transplantation of fetal neural tissue has been demonstrated to prevent neuronal
      loss in a number of CNS injury models including spinal cord contusion. However,
      no studies have examined the neuroprotective role of fetal transplants in models
      of traumatic brain injury. The present study examined the ability of fetal neural
      grafts to attenuate neuronal loss resulting from lateral fluid percussion (FP)
      brain injury in the rat. Lateral FP in the rat elicits a focal contusion within
      the parietal/temporal cortex and induces cell death in a subset of hippocampal
      CA3 pyramidal neurons. To examine potential neuroprotective effects of fetal
      neural grafts, either E16 fetal hippocampus, E16 fetal cortex, or sterile
      lactated Ringers was stereotaxically transplanted directly into contused cortex 2
      days after FP brain injury. The effects of fetal transplants upon adjacent
      injured hippocampal CA3 regions were then assessed at 4 weeks after grafting
      utilizing quantitative image analysis. Both fetal cortex and hippocampal grafts
      survived within contused cortex. Fetal hippocampal grafts significantly
      attenuated CA3 cell death resulting from lateral fluid percussion, while fetal
      cortical transplants induced a small, but nonsignificant, amelioration of CA3
      pyramidal loss. Thus, neuroprotection by fetal grafts appeared to be tissue
      specific with hippocampal, but not cortical, fetal transplants significantly
      reducing posttraumatic CA3 loss. In summary, fetal neural transplantation can
      ameliorate hippocampal cell death following experimental brain injury.

PMID- 8742135
TI  - The effect of the adrenocortical axis upon recovery from closed head injury.
AB  - Fragments and analogs of the hormone ACTH were previously shown to have
      beneficial effect on the outcome of head injury, while elevated levels of
      corticosterone (CS) exacerbate it. In the present study we investigated the role
      of the hypothalamo-pituitary-adrenal (HPA) axis in the pathophysiology of closed
      head injury (CHI). CHI was produced in ether-anesthetized rats by a calibrated
      weight-drop device. After evaluating the functional status according to a set of
      criteria, at 1 and 24 h, the rats were sacrificed and cortical tissue was removed
      to determine its water content. CHI was also produced in rats that underwent
      surgical procedures to remove their adrenal gland (ADEX) or the pituitary
      (HypoX), thus altering the levels of their circulating HPA hormones. Given after
      CHI, to rats with intact HPA axis, ACTH reduced edema and improved recovery. ADEX
      rats (6 days postsurgery) had 10-fold higher levels of plasma ACTH. ADEX rats
      subjected to CHI showed improved functional outcome (p = 0.008) and reduced edema
      (p = 0.02). We then produced CHI in three groups of rats: HypoX (15 days
      postsurgery), HypoX treated with ACTH, and controls. In HypoX rats, CHI resulted
      in increased mortality (35% vs 0) and edema in the surviving rats, and a slower
      recovery, as compared with the control. Mortality was prevented, edema slightly
      reduced, and recovery significantly improved after administration of 1-24-ACTH to
      HypoX rats with CHI. Our results suggest that ACTH has a cerebroprotective effect
      on the outcome of CHI.

PMID- 8742136
TI  - [The necessary updating of primary care].

PMID- 8742137
TI  - [Evaluation of an informative leaflet on AIDS/HIV infection aimed at primary
      health care professionals in Catalonia].
AB  - OBJECTIVE: To assess primary care professionals' understanding and acceptance of
      a periodic information leaflet on HIV/AIDS. DESIGN: Crossover. SETTING: Primary
      care teams from the Institut Catala de la Salut. PARTICIPANTS: A random sample of
      300 doctors, qualified nurses and social workers. INTERVENTION: A self
      administered, anonymous questionnaire returned by normal post. MEASUREMENTS AND
      MAIN RESULTS: Questions covered the following thematic areas: clinical care of
      people infected by HIV/AIDS and requests for diagnostic tests for infection,
      perception of skills in the promotion of changes in patients' sexual behaviour
      and drug use, providing psychological support and guidelines for integrating HIV+
      children in schools and information on social resources. 60% knew the
      publication. Thematic areas which aroused most interest were: psychological
      support for people affected, prevention of HIV infection in the health
      environment, clinical advice and diagnosis. 77% had received requests for
      diagnostic tests and 88% had attended infected people. CONCLUSIONS: In spite of
      the low reply rate (50%) and relative variability among the professionals and the
      health regions they came from, this first assessment enabled us to identify
      specific educational needs in the care and prevention of HIV/AIDS infection in
      the primary care framework and also to improve the distribution methods we used.

PMID- 8742138
TI  - [Additional question ("is there anything else...?") in primary health care].
AB  - OBJECTIVES: To assess in two General Medicine clinics the use of the formula "Was
      there anything else?" in connection with patients' additional requests and the
      question's possible association with other variables. DESIGN: Quasi-experimental.
      SETTING: Urban Health Centre. PATIENTS: Patients from two lists attending over a
      two-month period, with the exclusion of scheduled patients without appointments.
      MEASUREMENTS AND INTERVENTIONS: For one of the months patients were asked: "Was
      there anything else?" (intervention group) and for the other month, they were not
      (control group). On each visit variables were recorded: list, doctor
      (tutor/intern), age, gender, reason for consultation (pathology/burocratic),
      whether accompanied, waiting time and additional requests (new problems raised at
      the end of the visit). A bivariant analysis of each of the variables with the
      variable 'intervention' was made and, after a prior transformation of the
      variable 'additional requests' into two, was adjusted to a multiple logistic
      regression model in order to control the confusion. RESULTS: 2,657 attendances
      were analysed. The variables which were significant for the prediction of
      additional requests were: intervention, list, age, gender and reason for
      consultation. CONCLUSIONS: The intervention of the doctor may generate additional
      requests, although whether this means that the consultation is better organised
      remains to be assessed.

PMID- 8742139
TI  - [Dry eye syndrome: etiopathology and clinical forms].

PMID- 8742140
TI  - [Screening for glaucoma in diabetic patients by using the Schiortz tonometer].
AB  - OBJECTIVES: To assess the usefulness of measuring in primary care the intraocular
      pressure (IOP) of diabetics as a glaucoma screening test, validating the Schiortz
      tonometer for this end. To analyse the prevalence of glaucoma and associated risk
      factors in our diabetic population. DESIGN: An observational crossover study.
      SETTING: Primary Care. Concentaina Health Centre. PATIENTS: 144 patients in our
      centre's diabetes mellitus health programme. MEASUREMENTS AND MAIN RESULTS: There
      were 31 cases of IOP over 20 mmHg measured with the Schiortz tonometer, on whom
      the ophthalmologist repeated the measurement with the Perkins tonometer, i.e.
      viewing the back of the eye to confirm the existence of papillary cupping
      consistent with the presence of Glaucoma. We chose a group with normal IOP,
      homogeneous with the group with high IOP to validate the Schiortz tonometer,
      using as confirmation the results obtained by the ophthalmologist with the
      Perkins tonometer; and as confirmation in the detection of glaucoma, finding
      papillary excavation in the binocular ophthalmoscopy. Prevalence of glaucoma was
      11%, which was 75% in the newly diagnosed cases. The positive predictive value of
      the Schiortz tonometer in detecting increases in IOP was 87.1%, and with respect
      to the detection of glaucoma, it was 35.5%. CONCLUSIONS: The high prevalence of
      glaucoma in diabetic patients justifies the systematic study of this risk factor.
      The Schiortz tonometer is a useful and valid method, that can be used in primary
      care for glaucoma screening in this population group.

PMID- 8742141
TI  - [Professional profile of primary health care personnel. A Delphi study].
AB  - OBJECTIVE: To determine the professional profile of health staff (doctors,
      paediatricians and nurses) in primary care (PC). DESIGN: Three simultaneous
      Delphi techniques (consensus method). SETTING: Primary care. PARTICIPANTS: 55
      doctors, 45 nurses and 23 paediatricians from the whole of Spain and different
      fields of activity. INTERVENTION: The filling in of three questionnaires, using
      the Delphi methodology. RESULTS: The overall percentage of replies was 69.1%
      (first questionnaire), 70.7% (2nd) and 60.16% (3th). The PC doctor should guide
      in a suitable way his/her community's health problems, using the relevant
      diagnostic and therapeutic methods, caring for patients' all-round health,
      controlling the doctor-patient interview, all in collaboration with other
      professionals, with a planning, programming and evaluation of his/her activity
      and a basically community-oriented approach. The nursing professional should
      provide all-round care for patients, using nursing diagnostic and therapeutic
      methods, within a multidisciplinary team and carrying out planning, programming
      and evaluation of the community's health problems. The PC paediatrician should be
      concerned with the prevention and treatment of the most common pathologies.
      He/she has a vital role to play in childrens' health education, should have the
      training to resolve the most common paediatric emergencies and organise his/her
      work within a multidisciplinary team. CONCLUSIONS: The Delphi method is a useful
      technique for determining professional profiles. Paediatricians have a more
      sharply defined profile than doctors and nursing staff.

PMID- 8742142
TI  - [Causes of non-compliance and associated factors in non-attendance of scheduled
      consultation].
AB  - OBJECTIVE: To find the degree of non-attendance at scheduled consultations and
      associated factors, with the aim of introducing the necessary corrective
      measures. DESIGN: An analytic observational study. SETTING: Silleria Health
      Centre, Toledo. PATIENTS: People on a medical list with scheduled medical and/or
      nursing appointments over the period of a year. MEASUREMENTS AND MAIN RESULTS:
      There were 253 cases of non-attendance (13.16%) out of a total of 1,922 scheduled
      consultations. Different variables were analysed, with statistically significant
      results being found in user's age and profession (p < 0.01), season of the year
      (p = 0.00067), the number of previous appointments (p < 0.01) and the number of
      previous non-attendances (p < 0.001). A profile of the non-attender emerged as: a
      young person, unemployed or student, single or separated, with average or higher
      education and who makes an appointment for control of risk factors
      cardiovascular, to open a medical history or for pregnancy monitoring.
      CONCLUSIONS: The level of attendance using present appointment methodology is
      acceptable. Nevertheless we believe a change of strategy, which would involve the
      community more both in preventive activities and in taking responsibility for
      their own attendance is needed.

PMID- 8742143
TI  - [Management and monitoring of transient work incapacity. Is the primary care
      model effective?].
AB  - OBJECTIVES: To clarify differences between the short-term sick notes issued by
      the two models of primary care--the new model (NM) and traditional model (TM)-
      and to identify possible conditioning factors. DESIGN: An observational
      descriptive study of a crossover type. SETTING: Two base health districts in
      Madrid's Area 11. PATIENTS AND OTHER PARTICIPANTS: 31 general practitioners, who
      issued 3,508 short-term sick notes during 1992. MEASUREMENTS AND MAIN RESULTS:
      Patients' variables taken from the P-14 cards of the Medical Inspections were:
      age, gender, diagnosis and length of time off. Professionals' variables were:
      age, gender, their job context and training. There were no clear differences in
      the number of short-term sick-notes issued by the two models, nor in patients'
      characteristics. There were differences in the failure to fill in the diagnosis,
      and in its distribution. There was also a difference in the length of the
      illnesses, which was more acute for the longer events. Though patients'
      characteristics were similar, those of professionals were not. The logical
      correlation between the variables relating to the professionals was confirmed by
      multivariant analysis. The profile of the NM professional could be simplified to:
      younger doctors, and training in family and community medicine. If possible
      influences of age and training were eliminated, the differences in length of time
      off were not significant. CONCLUSIONS: The differences found by our study in the
      length of short-term time off work could be attributed to characteristics
      inherent to the care model.

PMID- 8742144
TI  - [Proposal for a new classification of long-term treatment in primary health
      care].
AB  - OBJECTIVE: To evaluate the suitability of medication for an automatised
      dispensing system (ADS) for prescriptions by means of an indicator specially
      designed for this study. DESIGN: A descriptive, crossover study of the medicines
      contained in our ADS. SETTING: Raval-Sud Basic Health District, Barcelona.
      MEASUREMENTS AND MAIN RESULTS: The indicator was designed and its categories
      determined through the interaction of the following variables for each medicine:
      its most usual indication, length of treatment, intrinsic value and the
      theoretical source of prescription. Then all the medicines included in the ADS
      were codified and analysed with a computer program. The 728 analysed were
      classified in 8 different categories: those for acute pathology (32%), for
      subacute or acute pathology requiring long-term treatment (potentially chronic
      indication) (9%), for chronic pathology controlled at the primary care level
      (22%), for chronic pathology controlled in the hospital context (12%), for mental
      pathology (8%), for chronic pathology well controlled but with a low intrinsic
      value (3%), medicines of low intrinsic value for chronic pathology (degenerative
      pathology) without recognised pharmacological alternatives which the family
      doctor or specialist can prescribe (14%). CONCLUSIONS: If medicines were better
      defined and codified, the proposed indicator would facilitate rapid
      discrimination of different groups of drugs' suitability or otherwise for ADS.

PMID- 8742145
TI  - [Analysis of the use of radiology in primary health care].
AB  - OBJECTIVE: To analyse the quality of requests in primary care for radiological
      investigations, by determining both their effectiveness and modifications in the
      doctors' therapeutic approach and diagnostic opinion caused by the radiological
      findings. DESIGN: Longitudinal, retrospective study. SETTING: The Embajadores 1
      Primary Care team (PCT), Madrid, during 1993. PARTICIPANTS: 203 radiologies on a
      significant sample of the PCT's catchment population with a clinical history.
      MEASUREMENTS AND RESULTS: Radiology was requested for 12% of patients seen: males
      39.40% and women 60.59%. Average age was 56.64 +/- 1.41. Commonest requests were
      for: bone (41.87%), thorax (25.12%), abdominal ecography (9.36%) and digestive
      system (8.37%). Pathology was discovered in 67.98% of cases, with these results
      considered relevant in 26.60%. The radiological findings caused 18.72% of doctors
      to change their therapeutic approach or diagnostic opinion. The radiological
      investigations with most relevant findings were: mammographies (38.46%), barium
      meals (35.29%) and abdominal ecographies (31.57%). CONCLUSIONS: Bone and thoracic
      radiologies account for almost 70% of requests. Despite the high percentage of
      pathological radiographies, only 19% of the x-rays caused any change in the
      doctor's attitude, which makes us think the correct indication for each case must
      be analysed.

PMID- 8742146
TI  - [Anxiety and depression in type II diabetics].
AB  - OBJECTIVES: To find the prevalence of depression and the level of anxiety in a
      group of patients with diabetes mellitus type II (DM); to compare the presence of
      psychiatric pathology with different variables and contrast the diabetic group's
      results with those of a group of non-diabetic patients. DESIGN: A comparative
      crossover study. SETTING: The Ronda Prim Health Centre, Mataro. PATIENTS AND
      OTHER PARTICIPANTS: The diabetics controlled of 4 of the 6 Basic Care Units (BCU)
      of our Centre. The comparison group consisted of 85 patients who attended the
      Centre of their own accord, matched for gender, age and BCU. The two groups did
      not differ as to socio-economic level, marital status and job. MEASUREMENTS AND
      MAIN RESULTS: Two self-applicable tests were given to all the patients: the Stai
      test to measure anxiety and the Beck one to determine depression. 27% of the
      diabetic patients had depression, as against 47% of those in the comparison group
      (p = 0.001). For the diabetic group, depression and anxiety level was found to
      have no relationship with the length of the DM's development, its treatment and
      chronic complications, the performance of self-analysis techniques and glycaemic
      control. CONCLUSIONS: The group of diabetics studied displayed a prevalence of
      psychiatric pathology very much lower than the control group. No statistically
      significant relationship was found between depression and anxiety levels, and
      different variables associated with DM.

PMID- 8742147
TI  - [Infectious diseases in primary care].
AB  - OBJECTIVE: To find the frequency and seasonal variability of the infectious
      diseases detected over a year. DESIGN: Observational prospective study. SETTING:
      Primary care centre. PATIENTS: Simple multi-stage random sampling of the patients
      over 14 seen on demand at general medical clinics and the Casualty department
      between June 1991 and May 1992. MEASUREMENTS AND MAIN RESULTS: Out of 49,193
      attendances during the study period, the attendance sample was 2,523, of which
      474 (18.8%; CI: 17.3-20.3%) were for infectious conditions. Average age of these
      474 was 39 (SD: 19.17); 55% were women. Frequency of respiratory infections was
      64.1% (CI: 59.8-68.5%). The correlation coefficient between respiratory
      infections and the total number of infections was 0.94 (R2 = 0.89). The frequency
      of infections oscillated between 29% (CI: 23-35%) in February and 10% (CI: 5.8
      14.5%) in May. CONCLUSIONS: Infectious conditions account for a considerable
      percentage of the total number of primary care attendances. There is a seasonal
      variation in infections, which is mainly due to respiratory infections.

PMID- 8742148
TI  - [Clinical approach to physiologic dispnea in pregnancy].

PMID- 8742149
TI  - [Classification systems in case-mix groups in ambulatory care. Perspectives for
      our primary health care].

PMID- 8742150
TI  - [Methods of vaccination against Hemophilus influenzae type B].

PMID- 8742151
TI  - [Is clinical pharmacology important in primary health care? The Mallorca
      experience].

PMID- 8742152
TI  - [Macroangiopathy in adult diabetics].

PMID- 8742153
TI  - [Oral contraceptives and eye diseases].

PMID- 8742154
TI  - Years of potential life lost and lost future productivity due to occupational
      fatalities--Alaska, 1990-1994.
AB  - INTRODUCTION: Alaska had the highest occupational fatality rate of any state for
      the 1980s. The impact of these events is estimated by the index of years of
      potential life lost before age 65 (YPLL), which was developed to measure the
      potentially preventable mortality occurring early in life. METHODS: Lost future
      productivity (wages) and YPLL were calculated from surveillance statistics for
      all workers killed on the job during this 5-year period. RESULTS: During 1990
      1994, Alaska experienced 343 work-related deaths among civilians under age 65.
      YPLL was 9,690 years with an estimated lost future productivity of $367,000,000.
      DISCUSSION: Premature death due to occupational traumatic injury in Alaska for
      1990-1994 was extremely costly to society. Premature death not only adversely
      affects the deceased workers' family, friends, and coworkers, but also society
      economically. Effective intervention strategies are needed to significantly
      reduce both the number and the cost of fatal occupational trauma in Alaska.

PMID- 8742155
TI  - Home health care for cancer patients: insights from the American Indian
      community.
AB  - With the confounding effects of an aging population, as well as advances in the
      treatment of cancers, the cure rates and associated recovery time for patients
      have increased. In the past, recovery from cancer treatment was often associated
      with extended hospital stays. However, shorter lengths of stay and the use of
      home health care is now the accepted standard of care. For the recovering
      patients, and their families, sensitivity to their cultural needs may often be
      overlooked given the diverse nature and background of home health care providers.
      Within the Indian Health Service, the cultural needs of the patients are taken
      into account. Through this paper we hope to provide a description of this unique
      program of home health care for American Indians who live on or near reservations
      and trust lands and Alaskan Natives who live in traditional villages.

PMID- 8742156
TI  - Home care for native American cancer patients: an oncologist's perspective.

PMID- 8742157
TI  - Native American data limitations and home care.

PMID- 8742158
TI  - American Indian families and home care: macro social and cultural considerations.
AB  - Administration on Aging and the Indian Health Service are developing or examining
      the feasibility of programs to support home health care on reservations and
      American Indian colleges are training home care paraprofessionals to provide high
      quality home care for frail American Indian elders. Home care links formal and
      informal systems of health care and is affected by social and cultural issues.
      These macro-level considerations provide a context for home care of cancer
      patients and are the focus of this article.

PMID- 8742159
TI  - Group A beta hemolytic streptococcus pharyngitis in United States Coast Guard
      units in Sitka.

PMID- 8742160
TI  - Interstitial pulmonary fibrosis--presentation in aviation medicine.

PMID- 8742161
TI  - The relationship of episiotomy to third and fourth degree lacerations.
AB  - Third and fourth degree lacerations can produce significant long term morbidity
      to women undergoing childbirth. The incidence of third and fourth degree
      lacerations is variable depending on the institution and the obstetrical
      provider. While episiotomy remains a valuable intervention in selected cases, an
      improvement program directed at lowering the use of episiotomy can reduce the
      incidence of this clinical event. Hospitals and physicians with higher rates of
      third and fourth degree tears should examine the use of episiotomy, and midline
      episiotomy in particular, which is associated with an increased incidence of
      third and fourth degree tears.

PMID- 8742162
TI  - Headache--an important symptom.

PMID- 8742164
TI  - Arkansas HIV/AIDS report 1983-1996.

PMID- 8742163
TI  - The monoclonal antibody, 7E3 and treatment of coronary artery disease.

PMID- 8742165
TI  - Radiological case of the month. Cystic adenomatoid malformation.

PMID- 8742166
TI  - Fluorescent probes and flow cytometry: new insights into environmental
      bacteriology.
AB  - Recent trends in flow cytometry have established new techniques in bacteriology.
      Advances in fluorescent dye technology complement these improvements, offering
      probes for a variety of cellular functions. Bacterial ecology requires the
      application of new techniques to help answer questions unanswerable by
      traditional methods alone. Here we review some aspects of how coupling the two
      technologies has enabled researchers to directly study individual bacterial
      cells, and revealed the complexity and heterogeneity present in both laboratory
      cultures and in environmental samples. Results are discussed with respect to
      viability analysis, stress induced changes, specific cell detection and cell
      sorting.

PMID- 8742167
TI  - Flow cytometry of mesophyll and bundle sheath chloroplast thylakoids of maize
      (Zea mays L.).
AB  - Chlorophyll fluorescence at short and long wavelengths was used to sort thylakoid
      membranes of maize, a plant with the C4 dicarboxylic acid pathway of
      photosynthesis, in a flow cytometer. The method yielded two distinct particle
      populations that were identified as mesophyll and bundle sheath thylakoids by low
      temperature fluorescence spectroscopy and by the pigment ratio of chlorophyll
      a/b. Mesophyll and bundle sheath thylakoids were essentially pure after sorting
      by flow cytometry. Fluorescence data and chlorophyll a/b pigment ratios of
      thylakoids separated by flow cytometry were compared with earlier data of
      preparations obtained by conventional isolation procedures. Our results indicate
      that impure mesophyll and bundle sheath membranes were used in most previous
      investigations. We were unable to detect the major light-harvesting complex of PS
      II (LHC II) in our pure bundle sheath thylakoids using fluorescence excitation
      spectroscopy. Therefore, we believe that the previously reported presence of LHC
      II in bundle sheath chloroplasts of maize can be attributed to mesophyll
      contamination.

PMID- 8742168
TI  - DNA ploidy analysis by laser scanning cytometry (LSC) in colorectal cancers and
      comparison with flow cytometry.
AB  - We evaluated laser scanning cytometry (LSC) by comparing nuclear DNA ploidy
      determined by LSC and by flow cytometry (FCM) in 77 samples of human colorectal
      cancer from 48 patients. Both methods revealed an aneuploid peak in 30 (62.5%) of
      the cases, although two samples that were aneuploid by LSC were diploid by FCM
      and two others were diploid by LSC and aneuploid by FCM. The concordance rate for
      nuclear DNA ploidy was 91.7% in the 48 patients and 87.0% for the 77 samples. The
      DNA index was also highly correlated between two methods (r2 = 0.97, P < 0.001).
      We concluded that LSC provides DNA histograms equivalent to FCM for surgical
      specimens and has potential clinical application in pathology.

PMID- 8742169
TI  - Effect of fixatives on calf thymocytes chromatin as analyzed by 3D high
      resolution fluorescence microscopy.
AB  - Two common fixatives--glutaraldehyde and ethanol/acetic acid mixture--were
      studied to understand their effects on DNA distribution inside the cell nucleus.
      Native calf thymocytes were analyzed by using a DNA selective fluorescent dye
      (DAPI) and computational optical sectioning microscopy on isolated cells before
      and after fixation. In order to estimate quantitatively the intranuclear DNA
      distribution, the stained calf thymocytes images were processed by removing the
      out-of-focus contributions present in each optical section. Although preliminary,
      the results show that within individual nuclei the frequency distribution of the
      fluorescence intensity appears significantly and differentially altered by the
      two fixatives. Namely with respect to the native unfixed preparation, the
      ethanol/acetic acid causes the complete disappearance of the higher intensity
      pixels, whereas glutaraldehyde fixation can be associated with the appearance of
      new ones of an even higher intensity. The quantitative analysis of the processed
      images allowed us to reconstruct the topological distribution of DNA inside the
      nucleus and to correlate the data with the results obtained by differential
      scanning calorimetry on similar samples.

PMID- 8742170
TI  - Quantitative determination of the MDR-related P-glycoprotein, Pgp 170, by a rapid
      flow cytometric technique.
AB  - Pgp 170 is the main integral membrane protein involved in acquired or de novo
      multidrug resistance (MDR), frequently implicated in chemotherapeutic failure.
      Because there is at present no method for quantitating Pgp 170 levels, a new and
      convenient assay, using flow cytometry with a standard fluorescence curve and MRK
      16, a mAb recognizing an external epitope of human Pgp 170, was developed.
      Assuming a 1:1 stoichiometry, we calculated for the first time the apparent
      number of Pgp 170 molecules per cell. The method was applied successfully to
      cells in suspension or grown as monolayers and their mixtures. All quality
      criteria were checked and proved the suitability of the method for quantifying
      Pgp 170.

PMID- 8742171
TI  - Induction of tetraploid DNA content by mutant simian virus 40 T antigen that has
      reduced complex formation with p53.
AB  - The 402 mutants (DE, DH, DN) of simian virus (SV) 40 form reduced levels of p53-T
      antigen complexes or no complexes in lytically infected cells (CV-1 cells)
      relative to wild-type (wt) virus when assayed by immunoprecipitation. When CV-1
      cells were infected with the 402 mutants, the cells were induced into multiple
      rounds of DNA synthesis without mitosis, resulting in a large population of cells
      with > G2 (tetraploid) DNA content similar to wt virus. The levels of T antigen
      and p53 per cell that were determined by flow cytometry were similar to wt
      lytically infected cells, with the levels of T antigen increasing as the
      infection proceeded. The p53 increased as the levels of T antigen increased,
      similar to a wt infection. These studies demonstrate that, in lytically infected
      cells with reduced p53-T antigen complex formation, the cells are induced into
      multiple rounds of DNA synthesis.

PMID- 8742172
TI  - Heterogeneity of B-lymphoid tumors in E mu-myc transgenic mice.
AB  - The clinically important issue of tumor heterogeneity was studied in C57BL/6-E mu
      myc transgenic mice, which provide a genetically uniform model system in which
      all animals eventually develop B cell lymphomas after additional genetic changes
      beyond enforced expression of the transgenic oncogene. Three different approaches
      were compared for discerning the cellular and genetic homogeneity of these
      tumors. Analysis of Igh gene rearrangement showed mainly monoclonality and only
      infrequent oligoclonality in the tumors from a given animal. In contrast,
      cytogenetic examination indicated a substantial degree of heterogeneity in the
      tumors from a given animal and showed that a wide variety of secondary genetic
      changes occur in E mu-myc transgenic mice. Flow cytometry of DNA content also
      revealed a high degree of heterogeneity within and among the tumor masses from
      single E mu-myc mice. Estimates of tumor heterogeneity revealed by these three
      techniques often did not coincide, indicating that these different approaches
      reflect distinct cellular parameters. Transgenic E mu-myc mice additionally
      homozygous for the scid mutation displayed enhanced levels of secondary genetic
      changes that were valuable for the methodological comparisons performed here, and
      demonstrated that the extent of tumor heterogeneity can be influenced by specific
      genes other than the primary E mu-myc transgene. In summary, a combination of
      methodologies appears to be required to reveal the full extent of tumor
      heterogeneity within a single individual.

PMID- 8742174
TI  - Identification of eosinophils by flow cytometry.
AB  - A flow cytometric method to identify and characterize eosinophils in lysed whole
      blood samples was established. A gating protocol was applied that in the first
      step uses the high autofluorescence and the high sideward scatter of eosinophils.
      In the second step, eosinophils were differentiated from neutrophils by lack of
      CD16 expression or alternatively presence of CD49d expression. Eosinophils
      purified by density gradient centrifugation (purity: 93% eosinophils contaminated
      with 7% neutrophils) were used to evaluate the technique. We were able to
      identify eosinophils added back to lysed whole blood samples and to identify
      partial degranulated eosinophils after treatment with secretory IgA and anti-IgA.
      In addition we were able to show that due to a large overlap of sideward scatter,
      the technique is applicable to purified normodense as well as hypodense
      eosinophils. In addition, there was a good correlation (r = 0.921, P < 0.0001)
      between the percentage of eosinophils determined by flow cytometry and
      microscopic evaluation in 81 patients. In patients with atopic dermatitis there
      was a reasonable correlation between a severity score (SCORAD) and the number of
      eosinophils determined by flow cytometry (R = 0.6107, P = 0017). Since the
      technique proved to be able to identify activated eosinophils bearing the CD69
      early activation antigen, the relation between serum creatinine and CD69
      expression on peripheral blood eosinophils was analysed showing a positive
      correlation (r = 0.4344, P = 0.016).

PMID- 8742173
TI  - Computer-assisted interpretation of flow cytometry data in hematology.
AB  - A computer program has been developed for computer-assisted diagnosis (including
      subclassification) of flow cytometry data of acute leukaemias and non-Hodgkin
      lymphomas by means of artificial intelligence. The knowledge base for the system
      has been formulated as semantic networks that describe physiological
      hematopoiesis as well as the pathological situation (e.g., aberrant antigen
      expression) of hematological disorders. The semantic networks reflect the
      hierarchy of cells and their occurrence in diseases, the normal and pathological
      antigen expression patterns of cells, cell maturation, and the frequency of cell
      populations in normal blood and bone marrow. Using these semantic networks, the
      diagnosis algorithm compares the characteristic antigen expression pattern of a
      disease with the actual findings in the blood or bone marrow sample. The
      algorithm can separate mixed populations by taking double staining findings into
      account. Finally, a diagnosis text is generated that describes all identified
      cell populations and the resulting diagnosis. The validation of the program
      showed a correct diagnosis (disease group and subclassification) in 97% of the
      cases (n = 633) with slight differences between the disease groups (e.g., B-NHL:
      99%, B-cell ALL: 84%).

PMID- 8742175
TI  - Lymphocyte fluorescence polarization measurements with the cellscan system:
      application to the SCM cancer test.
AB  - The SCM (Structuredness of Cytoplasmic Matrix) cancer test, a procedure based on
      detection of differences in lymphocyte activation between individuals with and
      without cancer, has remained controversial with inconsistent results reported by
      different authors. As originally described, the test includes two technically
      demanding steps, the first a lymphocyte separation procedure and the second a
      series of fluorescence polarization measurements. The Cellscan, a high-precision
      static cytometer system has been configured to perform the SCM test. The
      apparatus facilitates the polarization measurements and can analyze cells
      separated using simpler procedures than were originally described. Using methods
      and diagnostic criteria adapted for the Cellscan system, the SCM test correctly
      classified > 90% of patients with cancer and > 90% of individuals without cancer.

PMID- 8742176
TI  - Molar quantification by flow cytometry of fatty acid binding to cells using
      dipyrrometheneboron difluoride derivatives.
AB  - Fatty acid analogs of a dipyrrometheneboron difluoride fluorophore (BDY-FA) have
      recently been developed. Relative to other fluorescent fatty acids, some of these
      have the advantages of excitation and emission spectra similar to those of
      fluorescein and of high quantum yield, which permits their use in conventional
      argon laser cytometry or microscopy. For the cytofluorimetric quantification of
      BDY-FA analogs, expressed as molecules bound per cell, we have compared the
      fluorescence of BDY-dodecanoic acid (BDY-C12) with that of fluorescein.
      Fluorescent beads with different amounts of bound fluorescein were used to
      calibrate a flow cytometer in order to correlate the fluorescence intensity with
      the number of fluorescein molecules per bead. In addition, starting from the
      basic equation defining the relationship between fluorescence and concentration,
      we have derived another equation which makes it possible to establish, for a
      given fluorescence, the relative molar concentration of both fluorochromes and,
      consequently, to express the fluorescence intensity emitted by the BDY-FA as the
      equivalent number of BDY-FA molecules. As an example of the potential application
      of this procedure, the time-course and concentration-dependent binding of BDY-C12
      to quiescent and mitogen-activated human lymphocytes and to cultured human T
      lymphoma cells have been studied. The method described is of general interest as
      it can also be applied to the flow cytometric or laser scanning microscopic
      quantification of other fluorescent dyes.

PMID- 8742177
TI  - Flow cytometric criteria for assessment of silica--cell adsorptive interaction.

PMID- 8742178
TI  - [Humoral immunopathologic changes in the myocardium after clinical
      allotransplantation of the heart].
AB  - Endomyocardial diagnostic biopsies, recipient heart removed at operation,
      endomyocardial biopsies of allotransplants and postmortem material were studied
      using immunofluorescence to specify immunopathological process and to detect
      humoral rejection. Altogether 306 samples from 55 patients were studied. In the
      early postoperative period (one year) 8 out of 18 patients with heart transplants
      repeatedly showed immunopathologic picture of acute humoral (vascular) rejection
      which was characterized by a widespread immunoglobulin G and complement fixation
      in the capillary walls accompanied by enhanced capillary permeability and fibrin
      deposition in intestitial tissue. Such patients often had graft dysfunction. 1 to
      5 years after transplantation in 24 out of 37 patients discrete focal
      immunoglobulin and complement fixation was observed as one of chronic rejection
      component.

PMID- 8742179
TI  - [Ebstein's anomaly (morphologic and morphometric study].
AB  - 12 hearts with Ebstein's anomaly were studied. This disease is a combined anomaly
      of heart formation with dysplasia of the folds of the tricuspid valve (TV), its
      tendinous chordas and papillary muscles, dysplasia of the trabecular part of the
      right ventricle and dysplastic interrelationships between TV and the right
      ventricle: attachment by short chordas of posterior and septal folds of TV with
      the right ventricle walls, anomalous distal attachment of the anterior fold of
      TV. "Atrialisation" of the right ventricle is the reflection of the folds
      dysplasia the extreme form of which is the loss of communication between TV and
      trabecular part and formation of the direct communication between TV and the
      infundibular part of the right ventricle.

PMID- 8742180
TI  - [Nuclear ploidy in atrial cardiomyocytes in patients with heart disease].
AB  - The content of DNA and proteins has been studied morphometrically in
      intraoperative biopsies of patients of different ages with congenital heart
      diseases and rheumatic mitral stenosis. Hemodynamic hyperfunction provoked
      premature polyploidy of cardiomyocytes nuclei in children with congenital vitium
      cordis. In cardiomyocytes of 20-50-year-old patients with acquired vitium cordis
      polyploidy with an increasing age does not occur, but a decline in protein
      synthesis and intracellular edema are observed.

PMID- 8742181
TI  - [Role of blood-brain barrier disorders in the pathogenesis of alcoholic heart
      damage].
AB  - An experimental study of alcoholic heart damage was performed in 150 male rats of
      series I, II and III with modelled acute alcoholic intoxication, chronic
      alcoholic intoxication against developing abstinence syndrome, alcoholic
      abstinence syndrome, respectively. The degree of cardiomyocyte damage is largely
      determined by structural changes of histohematic barriers in alcoholic
      intoxication. Primary ethanol damage of the microcirculatory bed, that of
      perivascular connective tissue and sarcolemma result in a cardiomyocyte
      mitochondria damage and development of energetic deficiency. Atrophic and
      sclerotic alterations of the histohematic barrier develop in chronic alcoholic
      intoxication resulting in profound metabolic changes in the heart muscle and
      development of alcoholic cardiomyopathy. The damages to the histohematic barrier
      in abstinence syndrome result in catecholamine penetration into cardiomyocytes
      and development of focal necrosis in the myocardium.

PMID- 8742182
TI  - [Morphologic studies of bronchial biopsies in chronic bronchitis before and after
      treatment].
AB  - Bronchial biopsies in patients with chronic bronchitis were studied
      histochemically, light and electron microscopically before and after conventional
      treatment and combined therapy (standard regimen plus He-Ne laser puncture). The
      conclusion is made that the combined therapy is more effective especially at
      early stages of the disease when irreversible sclerotic changes in the submucosa
      and microcirculatory bed are absent. This therapy at early stages of the disease
      stimulates regeneration of the surface bronchial epithelium and facilitates
      reversibility of initial metaplasia.

PMID- 8742183
TI  - [Ultrastructure of bronchial blood vessels in chronic inflammation and
      endobronchial laser therapy].
AB  - Structural metabolic changes in the biopsies of the large bronchi mucous membrane
      were studied in 99 patients with chronic lung diseases. Progressing sclerosis of
      the connective tissue stroma resulted in the reduction of endotheliocyte
      metabolism which usually represent plastically active zone of the strom. This
      considerably influences basal cell proliferation resulting in changes of
      differentiation in bronchial epithelium. Endobronchial laser therapy induces
      proliferative and metabolic processes in the tunica propria of the mucous
      membrane. Congestion, intensive leucodia pedesis, leucocytic infiltrates and
      granulations develop in the mucous membrane, proliferative and metabolic activity
      of endotheliocytes and stromal cells increases this resulting in formation of
      fine fibrillar connective tissue.

PMID- 8742184
TI  - [Morphofunctional description of protective cell reactions in aspergillosis].
AB  - Pathomorphosis of aspergillosis was studied in 160 male guinea pigs which were
      given intraperitoneally a small dose (50000 conidia per 1 ml of isotonic sodium
      chloride solution) of Aspergillus fumigatus. Protective cell reactions under
      condition of a normal immune resistance are described. Immunological and
      mycological methods allowed one to reveal a variability of morphological changes
      at early stages of aspergillosis and to follow the development of secondary
      immunodeficiency on the disease day 14.

PMID- 8742185
TI  - [Morphofunctional features of fibroblasts in wound healing in old age].
AB  - Fibroblastic reaction in the course of posttraumatic repair of the skin in old
      rats is weaker and proceeds more slowly, the foci of active fibroblast
      proliferation are observed. The reduction of the fibroblast number in the wound
      in old rats is followed by an increase in their functional activity which,
      however, does not compensate for their quantitative decrease. Fibroblasts of old
      rats considerably vary in their structure and age-associated changes in their
      synthetic function are followed by disturbance of the secretory function.
      Intracellular development of collagen fibrils may occur under these conditions.

PMID- 8742186
TI  - [Importance of programmed endothelial death in the formation of intraorgan
      vascular bed in human embryogenesis].
AB  - The development of the intraorgan vascular bed is brought about by means of a
      loop-like vascular growth which forms not only arteries and veins of all levels
      but that of microcirculation system as well. Embryonal angiogenesis is followed
      by a programmed death of the endothelium of all autochtone structures and some
      functioning microvessels of a closed circulation. This process is of importance
      in remodelling of vascular bed and formation of collateral circulation and
      anastomoses.

PMID- 8742187
TI  - [Clinico-morphologic characteristics of primary hemochromatosis].
AB  - 12 autopsy cases of primary hemochromatosis were studied: 11 males (aged between
      29 and 69 years, mean age 51 years) and 1 57-year-old female. Clinical course in
      6 patients ran with predominant liver damage to the small nodule or was of
      biliary cirrhosis type, in 3 cases main manifestation was diabetes mellitus and
      in 3 cases cardiomyopathy. Generalized pattern of hemosiderine deposits with
      involvement of the liver, pancreas, heart, adrenals, pituitary, epiphysis,
      thyroid and other organs was established by the Pearl's test. Apart from pigment
      degeneration, atrophy and fibrosis, compensatory and regenerative changes were
      found. These changes should be taken into account when the disease is analyzed
      clinically and morphologically.

PMID- 8742188
TI  - [Morphologic features of mucosa and secretory activity of the stomach in patients
      with duodenal ulcers in obesity].
AB  - Gastric mucosa of obese patients with duodenal ulcer was investigated by means of
      light and electron microscopy and morphometrically. The comparison of the
      morphological findings and data on gastric secretion shows that overall volume of
      functional structures of the parietal and peptic cells providing secretion is
      smaller in duodenal ulcer patients with obesity than in non-obese patients.
      Elevated gastric secretion in these patients is maintained by hyperfunction of
      the corresponding structures.

PMID- 8742189
TI  - [Enzymic spectrum of preneoplastic and neoplastic changes induced by 1,2
      dimethylhydrazine in mouse kidneys].
AB  - Mouse renal cell tumors (RCT) were induced in male CBA male mice by 5
      subcutaneous injections of 8 mg 1,2-dimethylhydrazine (DMH) per kg body weight
      once a week. After a lag period of two years the kidneys were removed, and serial
      cryostat sections of the kidneys were histochemically analyzed for the following
      parameters: Glycogen content, basophilia, and activities of glycogen synthase
      (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6
      phosphate dehydrogenase (G6PDH), hexokinase (HK), pyruvate kinase (PK), lactate
      dehydrogenase (LDH), malic enzyme (ME), succinate dehydrogenase (SDH), alkaline
      phosphatase (ALPase) and glutamyl-transpeptidase (GGT). RCT displayed the same
      histochemical profile irrespective of their size and growth pattern. In
      comparison with normal kidney epithelium, the neoplastic cells exhibited elevated
      activities of enzymes for glycolysis (HK, PK LDH) and the pentose phosphate
      pathway (G6PDH) while negative G6Pase and low SDH activity were observed in these
      cells. The majority of RCT showed high PHO activity and weak staining for SYN.
      Activities of ALPase and GGT were negative in most of the RCT. Giant cells were
      detected in some large RCT. Higher activities of glycolytic and mitochondrial
      enzymes and G6PDH were found in giant cells compared with other tumor cells.
      Tubular preneoplastic lesions were similar to neoplastic lesions in morphological
      and histochemical characteristics. The present study revealed that a markedly
      elevated capacity for glycolysis and the pentose phosphate pathway occurred in
      renal cell tumors in mice. A similar histochemical pattern in the few
      preneoplastic tubular lesions observed suggests that these metabolic aberrations
      emerge early in carcinogenesis, but studies on earlier stages of renal
      carcinogenesis are needed to substantiate this assumption.

PMID- 8742190
TI  - [Ultrastructural changes in atria dna small intestines of suckling rabbits in
      experimental cholera].
AB  - 10-12-day old suckling rabbits received intragastrically culture of V. eltor 5879
      and the resultant ultrastructural changes in the small intestine, atrial
      cardiomyocytes and capillaries were studied. In the period of cholera vibrio
      adhesion (4 hours after the culture administration) epithelial cells underwent
      hydropic degeneration. Degenerative changes due to cell vacuolization and
      contractile alterations were noted in cardiomyocytes of both atria. The atrial Na
      uretic factor secretion prevailed over its synthesis in line with increased
      vascular permeability. The development of experimental cholera (on day 1-2) was
      characterized by balloon degeneration in the small intestinal epithelium.
      Numerous secretory granules were formed in the atrial cardiomyocytes without
      releasing peptides into the circulation. These changes are of compensatory nature
      and serve for liquid retention in the body. Microcirculatory disturbances take
      place at three levels: intravascular, endothelial and perivascular.

PMID- 8742191
TI  - [Morphologic changes in lens cells of the rabbit eye after irradiation with
      neodymium-YAG laser with wavelength 1.32 micrometers].
AB  - The exposure of the rabbit's lens to laser radiation (1.32 microns) induced
      complex damage probably due to heat-related changes in the lens fibers at the
      site of the beam action. Heating and coagulation of the tissues changed the
      position or led to the rupture of some lens fibers. Swelling of the fibers on the
      lens equator may result from damage to the cell membranes in the anterior part of
      the lens.

PMID- 8742192
TI  - [Generalized cryptococcosis in secondary immunodeficiency induced by long-term
      steroid therapy (on the 100th anniversary of the day of first discovery in
      1894)].
AB  - One case of a generalized cryptococcosis in secondary immunodeficiency resultant
      from a long-term steroid therapy is described. Granulomatous pulmonary lesion
      with subsequent abscess formation and generalized infection with involvement of
      the kidneys, pancreas and brain eventuated in the patient's death. Early
      intravital diagnosis of the lung mycotic damage and discontinuation of the
      hormonal therapy could essentially influence the disease outcome. It should be
      taken into account that immunity in such cases is not only the target of primary
      iatrogenic damage but also of a direct harmful action of the infectious agent
      itself, especially on T-cell immunity.

PMID- 8742193
TI  - [Brunner's gland adenoma of the duodenal bulb].
AB  - This rare tumor was found at surgery in a 35-year-old male operated for chronic
      ulcer of the duodenum complicated by gastrointestinal bleeding. The tumor looked
      like a pedunalated polyp 6 x 3 x 2 cm in size with an ulcer 0.5 cm in diameter.
      Histologically, the tumor was formed of large lobules of Brunner's glands, and
      its surface was lined with intestinal villi. Pascual's argyrophilic test
      discovered focal hyperplasia of endocrine cells in the intestinal lining. The
      majority of these cells, according to PAP reactions with antisera to
      polypeptides, were serotonin-positive. Among tumor cells somatostatine-positive
      cells were most numerous.

PMID- 8742194
TI  - [Thyroid gland ectopia at the base of the tongue].
AB  - At initial examination ulcer at the base of the tongue in a female of 25 years
      was diagnosed as a tumor. Further morphological investigation revealed the
      presence of the thyroid tissue while it was absent at the site of normal thyroid
      location. Most appropriate clinical and diagnostic approaches to this case are
      described which helped avoid unjustified surgery and related grave complications.

PMID- 8742195
TI  - [Brain tuberculoma in a child aged 1 year 1 month].
AB  - The paper reports a case of brain granuloma in a child aged one year and one
      month. Such tuberculomas are now a rare finding in childhood.

PMID- 8742196
TI  - [60th anniversary of the Chair of Pathology at Izhevsk Medical Institute].

PMID- 8742197
TI  - [Significance of somatometric analysis in medical research].
AB  - The literature data are presented on body weight and height changes in different
      population groups. Somatometria (particularly that of growing body allows one to
      determine the effect of each individual factor. Constitutional predisposition to
      certain diseases is conditioned by "the somatotype endocrinologic formula".

PMID- 8742198
TI  - [All-Russian methodologic conference on pathology in agricultural animals].

PMID- 8742199
TI  - Classics in Spine. Surgery literature revisited.
AB  - STUDY DESIGN: This article reviews the criteria for evaluating the quality of
      clinical trials. OBJECTIVES: To outline the current methodologic standards by
      which the validity of controlled trials need to be evaluated. SUMMARY OF
      BACKGROUND DATA: Weber's study, published in 1983 in Spine, is the only
      randomized trial comparing surgery and conservative management of sciatica in
      herniated lumbar discs. METHODS: Weber's article is revisited to illustrate basic
      principles in the design of clinical trials. RESULTS: Weber's study is a classic
      in spine surgery and has changed thinking regarding the benefit of surgery in
      sciatica related to herniated lumbar discs. However, the authors found
      potentially critical flaws in this study: a large number of crossovers,
      inadequate sample size, and insensitive outcome measurements. CONCLUSIONS: A
      randomized, controlled trial is the most rigorous way to evaluate health
      intervention. Despite the difficulties of performing such studies, investigators
      should use the most appropriate scientific methodology.

PMID- 8742200
TI  - Internal architecture of the thoracic pedicle. An anatomic study.
AB  - STUDY DESIGN: In this study, data are presented that provide the surgeon with
      additional information about the internal structure of the thoracic pedicle,
      which is especially useful for pedicle screw fixation in the thoracic spine.
      OBJECTIVES: To quantify the internal structure of the pedicle in the thoracic
      spine. SUMMARY OF BACKGROUND DATA: There are many studies describing the external
      dimensions of the thoracic pedicle (i.e., pedicle height, pedicle width, and
      pedicle axis in the transverse and sagittal planes). However, there is little
      reliable information concerning the internal structure of the pedicle. METHODS:
      Eighteen thoracic vertebrae were attached to a thin-sectioning machine and both
      pedicles were cut in six 1.0-mm thin slices. Slides of contact radiographs were
      rear-projected to a digitizer and the internal and external borders of the
      pedicle were digitized. Using special computer software, two external dimensions
      (i.e., pedicle height and pedicle width) and four internal dimensions (i.e.,
      cortical thicknesses of the superior, inferior, medial, and lateral walls) were
      calculated. RESULTS: The cancellous core was more than twice as large as the
      cortical shell, with a range from 65.6% to 78.6% with respect to the pedicle
      height, and 61.3% to 71.6% with respect to the pedicle width. The medial wall was
      between two and three times thicker than the lateral wall throughout all the
      pedicle slices and thoracic levels. These differences were highly significant (P
      < 0.001). CONCLUSIONS: The thoracic pedicle is a complex three-dimensional
      structure that is mostly filled with cancellous bone. The medial wall is
      significantly thicker than the lateral wall, which could explain the fact that
      most of the pedicle fractures related to pedicle screw insertion occur laterally.

PMID- 8742201
TI  - Herniated lumbar intervertebral discs spontaneously produce matrix
      metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2.
AB  - STUDY DESIGN: Herniated lumbar disc specimens were obtained from patients
      undergoing surgical discectomy for persistent radiculopathy and cultured in vitro
      to determine whether various biochemical agents were being produced. OBJECTIVES:
      Our hypothesis is that biochemical mediators of inflammation and tissue
      degradation play a role in intervertebral disc degeneration and in the
      pathophysiology of radiculopathy. SUMMARY OF BACKGROUND DATA: Low back pain with
      or without radiculopathy is a significant clinical problem, but the etiology of
      low back pain and the exact pathophysiology of radiculopathy remain elusive. The
      biochemical events that occur with intervertebral disc degeneration and, in
      particular, the role of biochemical mediators of inflammation and tissue
      degradation have received sparse attention in the literature. There is some
      preliminary evidence that inflammatory mediators may have an important role in
      the pathophysiology of radiculopathy. METHODS: Eighteen herniated lumbar discs
      were obtained from 15 patients undergoing disc surgery. The specimens were
      cultured and incubated for 72 hours, and the media were collected subsequently
      for biochemical analysis. Biochemical assays for matrix metalloproteinases,
      nitric oxide, prostaglandin E2, and a variety of cytokines were performed. As a
      control group, eight lumbar disc specimens were obtained from four patients
      undergoing anterior surgery for scoliosis and traumatic burst fractures, and
      similar biochemical analyses were performed. RESULTS: The culture media from the
      herniated lumbar discs showed increased levels of matrix metalloproteinase
      activity compared with the control discs. Similarly, the levels of nitric oxide,
      prostaglandin E2, and interleukin-6 were significantly higher in the herniated
      discs compared with the control discs. Interleukin 1 alpha, interleukin-1 beta,
      tumor necrosis factor-alpha, interleukin-1 receptor antagonist protein, and
      substance P were not detected in the culture media of either the herniated or
      control discs. CONCLUSIONS: Herniated lumbar discs were making spontaneously
      increased amounts of matrix metalloproteinases, nitric oxide, prostaglandin E2,
      and interleukin-6. These products may be involved intimately in the biochemistry
      of disc degeneration and the pathophysiology of radiculopathy. Their exact roles
      certainly need further investigation, but their mere presence implicates
      biochemical processes in intervertebral disc degeneration.

PMID- 8742202
TI  - The role of spinal instrumentation in augmenting lumbar posterolateral fusion.
AB  - STUDY DESIGN: Using a sheep model, clinically practical posterolateral
      intertransverse process fusion was successfully achieved and biomechanically
      tested to determine the load-sharing environment provided by spinal
      instrumentation and posterolateral fusion mass following solid arthrodesis.
      OBJECTIVES: To quantify the in vivo load-sharing capacity of spinal
      instrumentation on augmenting the posterolateral intertransverse fusion. The
      hypothesis was that transpedicular screw fixation maintains the biomechanical
      contribution to the posterolateral fusion stability even after successful
      arthrodesis because of its providing anterior and middle column support. SUMMARY
      OF BACKGROUND DATA: Although many previous studies have documented the biological
      and biomechanical advantages of posterolateral fusion, it is known that
      posterolateral fusion without spinal instrumentation allowed significant
      remaining motion at the fused segment even after the solid arthrodesis. Whether
      spinal instrumentation, especially transpedicular screw fixation, augments in
      vivo posterolateral fusion stability after solid arthrodesis has not been
      previously investigated. METHODS: Radiographic, macroscopic, and biomechanical
      analyses of a posterolateral intertransverse process fusion model were performed
      on 18 sheep at 4 months postoperatively. The load-sharing contribution of the
      spinal instrumentation was calculated based on the stability with or without
      spinal instrumentation tested in five loading modalities. Histomorphometry of the
      vertebral body spanned by spinal instrumentation provided the information
      regarding the biological effect of the load-sharing capacity of spinal
      instrumentation on bone remodeling. RESULTS: All sheep who received
      posterolateral intertransverse process fusion demonstrated successful solid
      arthrodesis and high biomechanical quality of the posterolateral fusion mass when
      compared to previous posterolateral fusion models. The significant difference in
      stiffness between fixation and subsequent fixation removal was observed in
      flexion, despite maintaining high lateral bending stiffness equivalent to the
      fixation (with instrumentation) level. This significant load-sharing contribution
      of spinal instrumentation detected in flexion corresponded to 27% when compared
      to the fixation level. The qualitative and quantitative bone histology showed 64%
      of the volumetric density of bone in the fixation group when compared to that of
      the sham group as well as narrow trabeculae and reduced connection of trabeculae.
      CONCLUSIONS: The continuance in support offered by transpedicular screw fixation
      was assured in vivo after the solid posterolateral intertransverse process
      fusion. This was clearly demonstrated under eccentric loads in a sagittal plane,
      suggesting that transpedicular screw fixation was able to provide anterior and
      middle column support and resist eccentric loads.

PMID- 8742203
TI  - Short-segment pedicle instrumentation. Biomechanical analysis of supplemental
      hook fixation.
AB  - STUDY DESIGN: This biomechanical study of fractures in cadaver vertebrae used
      specially designed pedicle screws to determine screw strains during loading of
      two different fixation constructs. OBJECTIVES: The authors determined the
      relative benefit of adding offset sublaminar hooks to standard pedicle screw
      constructs to reduce screw bending moments and prevent fixation failure and
      sagittal collapse. SUMMARY OF BACKGROUND DATA: Clinical studies have demonstrated
      a high incidence of early screw failure in short-segment pedicle instrumentation
      constructs used to treat unstable burst fractures. Strategies to prevent early
      construct failure include longer constructs, anterior strut graft reconstruction,
      and use of offset sublaminar hooks at the ends of standard short-segment pedicle
      instrumentation constructs. METHODS: Human cadaver spines with an L1 burst
      fracture were instrumented with a standard short-segment pedicle instrumentation
      construct using specially instrumented pedicle screws. Mechanical testing was
      carried out in flexion, extension, side bending, and torsion, and stiffness and
      screw bending moments were recorded. Offset hooks were applied initially, then
      removed and testing repeated. Stiffness data were compared to intact and
      postfracture results, and between augmented and standard constructs. RESULTS:
      Addition of offset laminar hooks, supralaminar at T11 and infralaminar at L2, to
      standard short-segment pedicle instrumentation constructs increased stiffness in
      flexion by 268%, in extension by 223%, in side bending by 161%, and in torsion by
      155% (all were significant except torsion). Sublaminar hooks also reduced pedicle
      screw bending moments to roughly 50% of standard in both flexion and extension (P
      < 0.05). CONCLUSIONS: Supplemental offset hooks significantly increase construct
      stiffness without sacrificing principles of short-segment pedicle
      instrumentation, and absorb some part of the construct strain, thereby reducing
      pedicle screw bending moments and the likelihood of postyield deformation and
      clinical failure.

PMID- 8742204
TI  - Biomechanical comparison of the dewar and interspinous cervical spine fixation
      techniques.
AB  - STUDY DESIGN: This study evaluates and compares the stiffness of two cervical
      spine fixation techniques. OBJECTIVES: This biomechanical study was carried out
      to compare the interspinous and Dewar cervical spine fixation techniques. SUMMARY
      OF BACKGROUND DATA: Interspinous wiring is a commonly used method of fixation in
      the cervical spine. The Dewar technique is less commonly known and practiced, and
      clinical experience has suggested that it may be a more stable technique.
      METHODS: Cervical spine specimens stabilized with the interspinous and "Dewar"
      techniques were biomechanically tested in flexion and in torsion. Stiffness and
      energy absorption under moderate loads were compared. The Dewar technique uses
      contoured double corticocancellous iliac grafts as internal grafts/splints fixed
      to the spine with threaded pins and wire. The interspinous technique is a single
      interspinous wire loop. Eleven fresh human cervical spines were harvested from
      cadavers. The spines were destabilized at C4-C5 by sectioning all tissue except
      the anterior longitudinal ligament. Each fixation technique was applied
      alternatively and tested on each spine. RESULTS: In torsion testing (n = 5), the
      Dewar fusion was 61% stiffer than the interspinous technique (P < 0.02). Dewar:
      11.3 N/mm (s.d. 4.9 N/mm) and interspinous: 8.4 N/mm (SD 3.3 N/mm). In flexion
      testing (n = 6), the Dewar technique was 35% stiffer than the interspinous
      technique (P < 0.10). Dewar: 655.4 Nmm/degree (SD 293 Nmm/degree) and
      interspinous: 406.8 Nmm/degree (SD 113.0 Nmm/degree). Energy absorption with the
      interspinous technique was greater in flexion (P < 0.10) and in torsion (P <
      0.005), indicating more deformation with the interspinous technique. There was no
      statistically significant difference between the means of specimens tested first
      and those tested second independently of the fixation technique. CONCLUSIONS:
      These tests indicate that the Dewar cervical spine fixation is stiffer than the
      single interspinous wire in both flexion and particularly torsion. This project
      is the only biomechanical study of the Dewar technique that we are aware of, and
      the results support the clinical findings regarding the effectiveness of this
      technique.

PMID- 8742205
TI  - Cervical discogenic pain. Prospective correlation of magnetic resonance imaging
      and discography in asymptomatic subjects and pain sufferers.
AB  - STUDY DESIGN: Asymptomatic subjects and chronic head/neck pain sufferers were
      studied with high-field magnetic resonance imaging and cervical discography to
      compare and correlate both tests. OBJECTIVES: To assess the accuracy of magnetic
      resonance imaging and discography in identifying the source(s) of cervical
      discogenic pain. SUMMARY OF BACKGROUND DATA: Previous retrospective studies
      describe a generally poor correlation between magnetic resonance imaging and
      provocative discography in the cervical spine. METHODS: Ten lifelong asymptomatic
      subjects and 10 nonlitigious chronic neck/head pain patients underwent
      discography at C3-C4 through C6-C7 after magnetic resonance imaging. Disc
      morphology and provoked responses were recorded at each level studied. RESULTS:
      Of 20 normal discs by magnetic resonance from the asymptomatic volunteers, 17
      proved to have painless anular tears discographically. The average response per
      disc (N = 40) for this group was 2.42, compared to 5.2 (N = 40) for the neck pain
      group. In the pain patients, 11 discs appeared normal at magnetic resonance
      imaging, whereas 10 of these proved to have anular tears discographically. Two of
      these 10 proved concordantly painful with intensity ratings of at least 7/10.
      Discographically normal discs (N = 8) were never painful (both groups), whereas
      intensely painful discs all exhibited tears of both the inner and outer aspects
      of the anulus. CONCLUSIONS: Significant cervical disc anular tears often escape
      magnetic resonance imaging detection, and magnetic resonance imaging cannot
      reliably identify the source(s) of cervical discogenic pain.

PMID- 8742206
TI  - Spinal intermittent claudication due to cervical and thoracic degenerative spine
      disease.
AB  - STUDY DESIGN: Neurogenic intermittent claudication can be caused by spinal cord
      compression. In this study, 20 patients with spinal intermittent claudication due
      to degenerative spine diseases were evaluated. OBJECTIVES: This study clarified
      the clinical features and pathomechanism of spinal intermittent claudication due
      to degenerative spine diseases. SUMMARY OF BACKGROUND DATA: Spinal intermittent
      claudication may either be produced by intrinsic or extrinsic lesions. Little is
      known about spinal intermittent claudication due to extrinsic lesions such as
      spinal cord compression. Twenty patients with spinal intermittent claudication,
      caused by cervical or thoracic lesions, who were given surgical treatment except
      for one, were studied. Their main subjective symptoms were tightness, weakness,
      and numbness in the lower limbs and a strangulated sensation in the trunk to
      lower limbs. The objective findings were occurrence and/or aggravation of
      spinothalamic signs. METHODS: The gait loading test was performed on these 20
      patients. Selective spinal angiography was performed on the patients with
      thoracic myelopathy and its therapeutic effects were evaluated. A radiographic
      assessment was made in all patients. RESULTS: The subjective symptoms and
      objective findings were reproduced by the gait loading test. Selective spinal
      angiography temporarily relieved or improved the spinal intermittent claudication
      due to the thoracic myelopathy. Spinal intermittent claudication disappeared
      immediately after surgical treatment. CONCLUSIONS: Circulatory impairment of the
      spinal cord seems to be closely related to the etiology of spinal intermittent
      claudication. Besides providing diagnostic information, selective spinal
      angiography may also have a temporary therapeutic effect.

PMID- 8742207
TI  - Segmental variations of bone mineral density in the cervical spine.
AB  - STUDY DESIGN: This study assessed the variability of segmental bone mineral
      density in the lower cervical spine (C4 through C7). A mean segmental bone
      mineral density value at each level was determined for all specimens, and a mean
      coefficient of variation among the 17 specimens was calculated. OBJECTIVES: To
      quantify the degree of intersegmental bone mineral density variations within
      cadaveric lower cervical spine segments. SUMMARY OF BACKGROUND DATA: Bone mineral
      density studies in the thoracic and lumbar spine have shown a high degree of
      variability between spinal segments; however, the extent of segmental bone
      mineral density variability in the cervical spine is unknown. METHODS: Seventeen
      human cadaveric cervical spine specimens (C4 through C7) were scanned in a water
      bath using dual energy x-ray absorptiometry in a lateral direction. Segmental
      bone mineral density of the vertebral bodies of all specimens were analyzed with
      respect to differences between segments within each specimen. RESULTS: The mean
      coefficient of segmental bone mineral density variations within each specimen for
      all spines was 14.8% (range, 5.8%-22.9%). Bone mineral density mean values and
      ranges at each level were as follows: C4, 0.720 g/cm2 (range, 0.367-1.161 g/cm2);
      C5, 0.784 g/cm2 (range, 0.348-1.268 g/cm2); C6, 0.735 g/cm2 (range 0.367-1.450
      g/cm2); C7, 0.590 g/cm2 (range, 0.340-1.040 g/cm2). Paired analysis of difference
      between all levels for 16 specimens demonstrated the bone mineral density at the
      C7 level to be significantly lower than at all other levels (P < 0.05).
      CONCLUSION: Our data show that significant interlevel bone mineral density
      variability exists in the lower cervical spine, and suggests that random single
      segment bone mineral density sampling or mean specimen bone mineral density
      values may not be relevant.

PMID- 8742208
TI  - Posterior cervical arthrodesis and stabilization with a lateral mass plate.
      Clinical and computed tomographic evaluation of lateral mass screw placement and
      associated complications.
AB  - STUDY DESIGN: A prospective study evaluating screw position and associated
      complications in 21 consecutive patients treated with a plate and screw fixation
      system applied to the lateral masses of the cervical spine. OBJECTIVES: To
      determine the clinical safety of lateral mass screws by determining their
      anatomic location and clinical complications in a consecutive patient series.
      SUMMARY OF BACKGROUND DATA: Lateral mass plating has been advocated for
      procedures in which wiring techniques cannot be used, especially in instances in
      which the posterior elements are deficient. METHODS: The first 21 consecutive
      patients who underwent posterior cervical arthrodesis and lateral mass plating
      with a single fixation system were reviewed prospectively. Computed tomography
      scans taken after surgery were reviewed independently by an orthopedic spinal
      surgeon and by a radiologist to evaluate screw tip position. Clinical and
      radiographic outcome was assessed at each visit after surgery. RESULTS: Ten of
      164 (6.1%) lateral mass screws were malpositioned in six patients. Three
      symptomatic patients underwent four additional operative procedures to remove or
      replace the malpositioned screws. All patients had radiographic union, and no
      patient developed mechanical implant failure requiring removal of
      instrumentation. Radiographic evaluation noted that 17% of the screws were in the
      central axial zone of the lateral mass on computed tomography. CONCLUSIONS:
      Lateral mass plating was associated with no vertebral artery or spinal cord
      injury. There was a 1.8%-per-screw risk of radiculopathy, which corresponds with
      published cadaveric studies. Radicular symptoms improved with screw removal in
      each case. The advantages of segmental fixation achieved with lateral mass plates
      and screws must be weighed against the risk of radiculopathy.

PMID- 8742209
TI  - Mechanics of the external fixation test in the lumbar spine. A roentgen
      stereophotogrammetric analysis.
AB  - STUDY DESIGN: By implanting tantalum indicators percutaneously during application
      of pedicular screws, lumbosacral mobility could be studied with roentgen
      stereophotogrammetric analysis in seven patients having a diagnostic external
      fixation test. OBJECTIVES: To determine the mechanical effects on the segmental
      mobility during an external fixation test of the lumbar spine. SUMMARY OF
      BACKGROUND DATA: External pedicular fixation test of the lumbar spine has been
      reported a valuable prognostic instrument in fusion for low back pain. METHODS: A
      Magerl external fixation device was applied in seven patients with low-grade
      spondylolysis-olisthesis. By using roentgen stereophotogrammetric technique, the
      intervertebral translations in the lumbosacral segment were determined. Each
      patient had three separate examinations; with the frame fixed, with the frame
      loosened, and without frame 6 weeks after screw removal. RESULTS: With the
      external frame fixed, the sagittal intervertebral translations were significantly
      reduced, in three cases to a level beneath the accuracy of the measuring method.
      One patient had the same immobilizing effect even with the frame loosened while
      for the others loosening of the frame meant regained mobility of the segment.
      CONCLUSION: The properties of the external fixator give an adequate mechanical
      basis for the prognostic external fixation test in lumbar fusion.

PMID- 8742210
TI  - Discographic pain report. Influence of psychological factors.
AB  - STUDY DESIGN: The possibility of a relationship between discographic pain
      responses and Minnesota Multiphasic Personality inventory scores was
      investigated. OBJECTIVES: To determine if patients with elevated Minnesota
      Multiphasic Personality Inventory scale scores were more likely to report pain on
      the injection of a nondisrupted disc than were patients without such high scores.
      SUMMARY OF BACKGROUND DATA: In general, injection into disrupted discs provokes
      pain, whereas injection into nondisrupted discs does not. However, discordant
      results are sometimes obtained and create a more difficult diagnostic challenge.
      METHODS: The primary study group was composed of 72 patients who underwent
      computed tomography/discography at the three lowest lumbar levels for diagnostic
      purposes and completed the Minnesota Multiphasic Personality Inventory. RESULTS:
      The mean scores on the Minnesota Multiphasic Personality Inventory
      hypochondriasis and hysteria scales were significantly greater for patients
      reporting reproduction of clinical pain than for patients not reporting pain on
      injection of a nondisrupted disc (hypochondriasis: 77.2 vs. 68.6, P < 0.01;
      hysteria: 74.5 vs. 68.3, P < 0.05). The scores on the depression scale followed a
      similar trend (68.6 vs. 63.6, P < 0.15). Multivariate analysis, adjusting the
      means for possible confounding effects of age, symptom duration, and sex, did not
      alter the results. CONCLUSIONS: Discographic pain reports are not only related to
      anatomic abnormalities, but are influenced by personality as assessed by the
      Minnesota Multiphasic Personality Inventory. Patients with elevated scores on the
      hypochondriasis, hysteria, and depression scales may tend to overreport pain
      during discographic injection. Among such patients, even those with a concordant
      computed tomography/discographic image, selection of therapeutic modalities
      should be made with caution.

PMID- 8742211
TI  - Acute severe low back pain. A population-based study of prevalence and care
      seeking.
AB  - STUDY DESIGN: Telephone interviews were conducted with a random sample of adults
      in 4437 North Carolina households. The response rate was 79%. OBJECTIVE: The
      prevalence of low back pain and the correlates of care-seeking in a defined
      population were examined. SUMMARY OF BACKGROUND DATA: Previous research on low
      back pain has used varying definitions of the illness of low back pain, and has
      admixed patients with acute and chronic low back pain. Acute low back pain was
      examined in this study as a distinct phenomenon separate from chronic low back
      pain. METHODS: Respondents completed a detailed interview regarding the
      occurrence of and care sought for back pain in 1991. Acute back pain was defined
      as functionally limiting pain lasting less than 3 months. RESULTS: From this
      sample, 485 individuals had at least one occurrence of acute severe low back pain
      in 1991, representing 7.6% of the adult population. Symptoms were reported less
      commonly in individuals older than age 60 years (5% vs. 8.5%) and in nonwhites
      compared with whites (5% vs. 8.5%). Thirty-nine percent of those with back pain
      sought medical care; 24% sought care initially from an allopathic physician, 13%
      from a chiropractor, and 2% from other providers. More prolonged pain, more
      severe pain, and sciatica were associated with care-seeking. Gender, income, age,
      rural residence, and health insurance status did not correlate with the decision
      to seek medical care. Younger age, male gender, and nonjob-related pain did
      correlate with the decision to seek care from a chiropractor. CONCLUSIONS: Acute
      back pain is common. Care is often sought regardless of income and insurance
      status. Seeing a health care provider for acute back pain may not be
      discretionary from the perspective of the patient.

PMID- 8742212
TI  - Pitfalls of patient education. Limited success of a program for back pain in
      primary care.
AB  - STUDY DESIGN: Low back pain patients seen in primary care were allocated randomly
      to one of two educational interventions or to usual care. OBJECTIVE: To evaluate
      educational interventions designed to improve the outcomes of primary care for
      low back pain. SUMMARY OF BACKGROUND DATA: Patients with back pain are frequently
      dissatisfied with their medical care and identify lack of information as the most
      insufficient aspect. METHODS: In a large Health Maintenance Organization clinic,
      293 subjects were allocated randomly to receive usual care, an educational
      booklet, or a 15-minute session with a clinic nurse, including the booklet and a
      follow-up telephone call. Outcome measures included satisfaction with care,
      perceived knowledge, participation in exercise, functional status, symptom
      relief, and health care use. Outcomes were assessed 1, 3, 7, and 52 weeks after
      the intervention. RESULTS: The nurse intervention resulted in higher patient
      satisfaction than usual care (P < 0.001) and higher perceived knowledge (P <
      0.001). Self-reported exercise participation was also higher in the nurse
      intervention group after a 1-week follow-up period (97% vs. 65% in the other
      groups; P < 0.0001). There were no significant differences among the three groups
      in worry, symptoms, functional status, or health care use at any follow-up
      interval. Differences in self-reported exercise and perceived knowledge were no
      longer significant after 7 weeks. CONCLUSIONS: These findings challenge the value
      of purely educational approaches in reducing functional impact or health care use
      related to back pain and also challenge the value of fitness exercise in the most
      acute phase of back pain.

PMID- 8742213
TI  - The effects of lumbosacral support belts and abdominal muscle strength on
      functional lifting ability in healthy women.
AB  - STUDY DESIGN: This study focused on lumbosacral support belts, abdominal muscle
      strength, and lifting ability in healthy women. Subjects underwent manual muscle
      testing to determine muscle strength and performed lifting procedures to
      determine lifting capacity. OBJECTIVES: The purpose of this study is threefold:
      1) to determine the effectiveness of lumbosacral support belts in improving
      lifting ability in healthy women, 2) to determine if lumbosacral support belts
      are more effective for those with weak abdominals than those with strong
      abdominals, and 3) to determine if the maximum amount of weight varies with
      abdominal muscle strength. SUMMARY OF BACKGROUND DATA: In a review of published
      literature, one study has addressed the relationship of lumbosacral support belts
      and lifting capacity. However, no study has examined the use of lumbosacral
      support belts and lifting capacity in a female population. METHODS: A convenient
      sample of 69 healthy women, aged 20 to 40 years, participated in this study.
      Subjects were categorized into one of three groups based on lower and upper
      abdominal muscle strength. Each subject then performed two lifting procedures,
      one with a lumbosacral support belt and one without, to determine two maximum
      lifts. RESULTS: Women between the ages of 20 and 40 years could lift
      approximately 1.0 kg more weight from the floor to waist height with the
      lumbosacral support belt. The maximum weight lifted varied with abdominal
      strength. Lumbosacral support belts were not more effective for those with weak
      abdominals than those with strong abdominals. CONCLUSIONS: When applied properly
      and used in conjunction with proper lifting technique, lumbosacral support belts
      slightly improved lifting ability in healthy women. The magnitude of the
      increase, although statistically significant, is not sufficient to advocate the
      use of lumbosacral support belts to increase lifting capacity.

PMID- 8742214
TI  - Reduction of high-grade spondylolisthesis using Edwards instrumentation.
AB  - STUDY DESIGN: Sixteen patients with high-grade spondylolisthesis (Grade III or
      higher) who underwent posterior decompression and reduction using the Edwards
      Modular Spine System (Spinal System Ltd., Baltimore, MD) were reviewed clinically
      and radiographically. OBJECTIVES: This study was undertaken to determine the
      efficacy of one specific reduction technique to treat patients with high-grade
      spondylolisthesis where there has been a loss of sagittal balance, intractable
      pain, and/or neurologic deficit. SUMMARY OF BACKGROUND DATA: The average age of
      our patients was 20 years. Preoperative slippage averaged 89%; preoperative slip
      angle averaged 50 degrees. Indications for surgery were back and leg pain,
      progression of slippage (in 9 patients), and/or the inability to stand upright
      with the knees straight. METHODS: Pre- and postoperative radiographic films were
      reviewed. The percent slip and the slip angle were measured pre- and
      postoperatively. Clinical data were obtained via chart review, telephone
      interview, and/or office visit. RESULTS: The average preoperative slip was 89%;
      postoperatively, the average slip was 29%. Slip angle averaged 50 degrees
      preoperatively and improved to a postoperative average of 24 degrees. Three
      patients had neurologic impairment postoperatively; one did not resolve. Four
      patients had hardware failure; all were revised. Ten patients had an excellent
      result, 5 patients had a good result, and 1 patient had a fair result. The
      average follow-up was 3.8 years. CONCLUSION: This procedure is technically
      demanding and is subject to the known risks of surgical treatment for high-grade
      spondylolisthesis. For select patients, it may be effective for reducing severe
      deformity and can be expected to afford good to excellent results. Improved
      sacral fixation may reduce the rate of hardware-related complications.

PMID- 8742215
TI  - Adolescent disc protrusions. A long-term follow-up of surgery compared to
      chymopapain.
AB  - STUDY DESIGN: This study compared chymopapain with primary surgery in the
      treatment of 60 radiologically proven adolescent lumbar disc protrusions and
      symptoms of low back pain and sciatica; the failures of intradiscal therapy were
      treated by surgical discectomy. OBJECTIVES: To establish whether chymopapain is
      as good as primary surgery in treating adolescents with proven lumbar disc
      protrusions. SUMMARY OF BACKGROUND DATA: Symptomatic lumbar disc protrusions are
      rare in white adolescents; the reported incidence varies from 0.8% to 3.2% of all
      lumbar disc protrusions. This is the largest study with long-term follow-up in
      the world literature. METHODS: Forty-two patients between the ages of 13 and 19
      years with proven lumbar disc protrusions were initially treated with
      chymopapain; the failures of intradiscal therapy were treated by surgical
      discectomy. Eighteen patients were treated with surgical discectomy. After
      initial review at 1, 3, 6, and 12 months, the patients were assessed using a
      postal questionnaire and telephone interview at a minimum of 5 years' follow-up
      (means: 8.5 years for chymopapain group, 7.2 years for surgery group). RESULTS:
      Full replies were received from 16 of 18 (89%) in the surgery group and 42 of 42
      (100%) in the chymopapain group. The long-term outcome is classed as good or
      excellent in 81% of the surgical group and 64% in the chymopapain group. If
      chymopapain is used as a first-line treatment, with surgery reserved for the
      failures, the long-term outcome is good or excellent in 82%. The chymopapain
      group had a shorter hospital stay. The surgical group were more likely to be
      unemployed and were less able to perform manual work and less able to engage in
      sporting activity. CONCLUSIONS: Back pain, radicular pain, and tension signs are
      common, but neurologic signs are less frequent in this age group. Long-term
      results of surgery are no better than the results of first-line chymopapain
      treatment with surgery being reserved for the failures. In 60% to 70% of
      patients, the morbidity, cost, and hospital stay were lessened. The patient is
      more likely to be in satisfactory employment after chemonucleolysis than after
      primary surgery.

PMID- 8742216
TI  - Open posterior dislocation of the lumbosacral junction. A case report.
AB  - STUDY DESIGN: A patient with open posterior dislocation of the lumbosacral
      junction is reported. OBJECTIVES: Treatment with primary anterior open reduction
      with internal fixation followed by delayed posterior stabilization and fusion.
      SUMMARY OF BACKGROUND DATA: This injury has been reported previously on two
      occasions; however, anterior stabilization was not used. In this case, anterior
      fixation was necessary because of the posterior soft tissue contamination.
      METHODS: After an anterior open reduction of L5-S1, stabilization was performed
      using instrumentation. Posterior wound care was then performed, with delayed
      posterior fusion and instrumentation of L5-S1 at 2 weeks. RESULTS: At 18 months
      there was solid fusion of the lumbosacral junction with no evidence of infection.
      CONCLUSIONS: Satisfactory results were obtained when principles of open fracture
      management were followed. Primary anterior stabilization allowed appropriate
      wound care. Definitive posterior stabilization and fusion can be done when soft
      tissue stability is obtained.

PMID- 8742217
TI  - Amyloidosis-related cauda equina compression in long-term hemodialysis patients.
      Three case reports.
AB  - STUDY DESIGN: These case reports illustrate the neurologic manifestations due to
      beta 2 microglobulin amyloid deposition at the lumbar spine level in long-term
      hemodialysis patients. OBJECTIVE: Radiologic investigations suggested the amyloid
      origin of extradural soft tissue deposition, which was confirmed by histologic
      examination after surgical excision. SUMMARY OF BACKGROUND DATA: Although
      cervical myelopathy is a recently recognized complication of long-term dialysis
      related beta 2 microglobulin amyloidosis, neurologic manifestations due to
      amyloid deposition at the lumbar spine level have rarely been reported. METHODS:
      Three case reports of cauda equina compression in long-term hemodialysis patients
      are presented. Follow-up radiography, computed tomography, and magnetic resonance
      imaging were performed and patients underwent surgical decompression of the
      thecal sac. RESULTS: In two patients, the compression resulted from the
      development of a destructive spondylarthropathy, and from the infiltration of
      extradural spaces and ligaments by an abnormal soft tissue. The third patient had
      lumbar spinal stenosis due to multiple disc protrusion and to hypertrophy of
      facet joints and ligamentum flavum. Multilevel laminectomies enabled excision of
      an abnormal fibrous tissue responsible for the thecal sac compression. Histologic
      examination of the excised fibrous tissues disclosed amyloid deposits in
      intervertebral discs, apophysial joints, and ligaments. CONCLUSIONS: In long-term
      hemodialysis patients, cauda equina compression may develop as the consequence of
      beta 2 microglobulin amyloid deposition in lumbar intervertebral discs, facet
      joints, and ligaments. Magnetic resonance imaging is well suited to show the
      extent of the compression and supports the argument for the amyloid origin of
      extradural soft tissue.

PMID- 8742218
TI  - Postsurgical ossified extradural cyst of the lumbar spine: a case report.
AB  - STUDY DESIGN: An extremely rare case of postsurgical ossified extradural cyst is
      reported. The imaging and intraoperative findings are described and compared with
      those in cases previously reported in the literature. OBJECTIVE: To draw
      attention to this rare but dangerous condition that can develop after lumbar
      surgery. SUMMARY OF BACKGROUND DATA: Only six cases of postsurgical ossified
      extradural cyst have hitherto been reported. METHODS: A 65-year-old man who had
      undergone surgery for a herniated lumbar intervertebral disc 20 years earlier
      complained of leg pain. From the imaging and intraoperative findings an ossified
      cyst with closed communicating aperture was diagnosed. The ossified cyst was
      surgically resected. RESULTS: Postoperatively, this patient was discharged and
      experienced alleviation of his symptoms. CONCLUSION: This case showed an
      extremely rare postsurgical ossified extradural cyst, and was of particular
      interest because in contrast to the previously reported cases the communicating
      aperture between the cyst and subarachnoid space was closed.

PMID- 8742219
TI  - Vertebral pneumatocyst. A case report.
AB  - STUDY DESIGN: This study illustrates intraosseous pneumatocyst of the vertebral
      body, a benign lesion. OBJECTIVES: To review the incidence and location of this
      benign lesion during a 1-year period. SUMMARY OF BACKGROUND DATA: Intraosseous
      pneumatocyst is a rare benign condition, commonly seen in iliac bone or sacrum.
      The etiology of this entity is unclear. Other locations of these lesions are very
      rare, and only a few isolated cases are reported in the literature. METHODS: In
      the last year (1994-1995), vertebral pneumatocyst was incidentally found in four
      patients who underwent computed tomography examination for presumptive discal
      lesion. Axial computed tomography with 2- and 4-mm slice thickness was performed.
      RESULTS: The typical computed tomography patterns of intraosseous pneumatocyst
      involving the cervical, dorsal, or lumbar spine were found. The bony structure
      and joints were normal. To the best of our knowledge, intraosseous pneumatocyst
      located in the spinal process has not been reported. CONCLUSIONS: Intraosseous
      pneumatocyst is a benign lesion. Biopsy and follow-up are unnecessary.

PMID- 8742220
TI  - Spine update. Impaired cognitive functioning after whiplash injury of the
      cervical spine.
AB  - To enhance the awareness of physicians treating whiplash patients, findings from
      previous research regarding cognitive functioning of these patients are discussed
      and recommendations for assessment provided. Cognitive disturbances (i.e.,
      deficient attentional functioning and impairment of memory) are frequent
      complaints in patients after whiplash injury. However, few prospective studies of
      nonselected patients have been performed. These studies indicate that impaired
      cognitive functioning relates either to trauma-induced somatic symptoms (i.e.,
      pain) or psychologic symptoms resulting from problems adjusting to trauma-related
      somatic symptoms. Accordingly, cognitive disturbances after whiplash show a fair
      rate of recovery, which parallels recovery from trauma-related somatic symptoms.
      Current research does not indicate disturbances in higher cognitive functions
      after whiplash.

PMID- 8742221
TI  - Victor Horsley's surgery for cervical caries and fracture. The Centennial
      Anniversary.
AB  - On August 25, 1895, Victor Horsley, the doyen of British neurosurgery, presented
      the results of his surgery for trauma and caries (tuberculosis) of the cervical
      spine at the Surgery Section of the British Medical Association Annual Meeting.
      All of the patients recovered from their operations and four were in attendance
      at the meeting to attest to the results of their operations. For the surgeon of
      1895, laminectomy of the cervical spine was a daunting undertaking. Although
      effective anesthesia and antiseptic techniques had become available,
      roentgenologic evaluation of spinal fracture and disease was still a future
      diagnostic modality. The special relationship of Victor Horsley with William
      Gowers, neurologist of Queen's Square Hospital, London, is presented. The status
      of therapy for cervical fracture and tuberculosis at the close of the 19th
      century is described to gauge the magnitude of this event as a major contribution
      to the progress of spinal surgery.

PMID- 8742222
TI  - Lumbar discography.
AB  - Lumbar discography has been suggested as a means of testing the lumbar disc as a
      source of back pain. While some clinicians believe that discography helps to
      identify conditions such as internal disc disruption, and to verify painful disc
      levels in anticipation of surgery, others find the test unproven and of
      questionable benefit. While the existence of internal disc disruption is itself
      hotly debated, Dr. Bogduk and Dr. Modic have focused on fundamental issues in
      formulating their opinions on the use of this modality. While both agree that
      prospective, controlled clinical trials are needed, Dr. Bogduk feels that the
      usefulness of discography has been shown and that the test provides valuable
      information to the clinician and the patient. Dr. Modic feels strongly that the
      test has no proven efficacy in improving patient outcomes, and feels, in fact,
      that it leads to inappropriate surgery.

PMID- 8742223
TI  - Kinetics of acetyl coenzyme A:arylamine N-acetyltransferase from rapid and slow
      acetylator frog tissues.
AB  - N-acetyltransferase (NAT) activity was determined in 100 frog (Rana tigrina)
      livers using 2-aminofluorene and p-aminobenzoic acid as substrates. Overall, the
      liver NAT activity of the 50 females was higher than the liver NAT activity of
      the 50 males. The activities (mean +/- SD) of NAT from the bladder, blood, colon,
      and liver of males was 0.30 +/- 0.11, 0.05 +/- 0.03, 0.09 +/- 0.05, and 0.93 +/-
      0.56 nmol/min/mg protein for the acetylation of aminofluorene and 0.29 +/- 0.06,
      0.36 +/- 0.04, 0.26 +/- 0.02, and 0.32 +/- 0.14 nmol/min/mg protein for the
      acetylation of p-aminobenzoic acid. In the bladder, blood, colon, and liver from
      female frogs, the activities obtained were 1.00 +/- 0.41, 0.52 +/- 0.07, 0.08 +/-
      0.05, and 1.27 +/- 0.49 nmol/min/mg protein for aminofluorene and 0.34 +/- 0.12,
      0.36 +/- 0.04, 0.34 +/- 0.07, and 0.48 +/- 0.21 nmol/min/mg protein for p
      aminobenzoic acid. Kinetic constants for arylamine NAT activity in the blood,
      liver, bladder, and colon from frogs with rapid, intermediate, and slow
      acetylator activities were determined. KM and Vmax values for aminofluorene were
      2- to 6-fold higher for liver than for the other tissues. KM and Vmax values for
      p-aminobenzoic acid showed a smaller variation among the tissues examined, with
      values obtained for the liver and bladder being somewhat higher than the values
      for the blood and colon. An apparent KM difference for aminofluorene was found in
      the liver from frogs with high and low acetylator activity. Based on the
      aminofluorene NAT activity of liver, there seems to be a polymorphism in NAT
      activity with 4 rapid, 21 intermediate, and 75 slow acetylators among the 100
      frogs assayed. Distribution of acetylator phenotypes was similar among the 50
      males and 50 females in this study. This is the first demonstration of acetyl
      coenzyme A:arylamine NAT activity in an amphibian and could lead to the
      development of a frog model for monitoring the effect of pollution of wetland
      environments on native species.

PMID- 8742224
TI  - Inhibition of the intestinal digoxin absorption and exsorption by quinidine.
AB  - Digoxin-quinidine interaction is well documented in the literature. The mechanism
      is, however, unknown. Previously, it was shown that quinidine reduced digoxin
      secretion by inhibiting P-glycoprotein (Pgp) in the renal tubule. Because Pgp is
      expressed in the small intestine to an extent no less than that in the kidney,
      the study was designed to investigate the possible effect of quinidine on the
      absorption and exsorption of digoxin in the rat intestine. Results from the
      everted sac study using different Pgp inhibitors and inducers support that
      digoxin is a substrate of Pgp in both jejunum and ileum. Plasma concentration of
      digoxin after intravenous administration increased 2-fold when 1 mg/hr quinidine
      was coinfused, whereas the amount that appeared in the intestinal lumen decreased
      by approximately 40%. In the presence of quinidine, total clearance decreased
      from 318.0 +/- 19.3 to 167.1 +/- 11.0 ml/hr, whereas intestinal clearance
      decreased from 28.8 +/- 1.7 to 11.1 +/- 1.6 ml/hr. In a separate study, 3H
      labeled digoxin was infused intravenously together with luminal perfusion of
      unlabeled digoxin in the intestine. The change of 3H-labeled digoxin
      concentrations in plasma and in the intestinal lumen was similar to those in the
      exsorption study. However, concentration of unlabeled digoxin in plasma or the
      intestinal lumen did not alter significantly with the addition of quinidine. The
      absorption clearance in the control group (N = 6, 6.4 +/- 0.47 ml/hr) was
      significantly higher than that in the group with quinidine coadministration (N =
      6, 4.8 +/- 0.31 ml/hr; p < 0.05). This indicates that quinidine may affect not
      only the elimination of digoxin, such as renal secretion, but also the
      absorption/exsorption of digoxin in the gastrointestinal tract. This study
      suggests that Pgp is involved in the drug interaction between digoxin and
      quinidine in the small intestine. It is clinically important to understand the
      effect of quinidine on digoxin absorption for further assessment.

PMID- 8742225
TI  - Tissue distribution and pharmacokinetics of centchroman. A new nonsteroidal
      postcoital contraceptive agent and its 7-desmethyl metabolite in female rats
      after a single oral dose.
AB  - This study reports assay methodology, tissue distribution, and the basic
      pharmacokinetic behavior of centchroman and its 7-desmethyl metabolite [7
      desmethyl centchroman (DMC)] after a single 12.5 mg/kg po dose in young female
      rats. Plasma, liver, lung, spleen, uterus, and adipose tissue were collected at
      various time intervals up to 14 days after dose. Reversed-phase HPLC, coupled
      with fluorescence detector, was used for simultaneous determination of
      centchroman and DMC in biosamples. The drug and metabolite were quantitated up to
      2 and 5 ng/ml in plasma and 10 and 20 ng/g in tissues, respectively. The assay
      method was validated in terms of accuracy, precision, interassay, and intraassay
      variability, and was found to be reliable and reproducible. Peak centchroman
      levels in all of the tissues were found between 8-12 hr, whereas DMC peaks
      appeared between 8 and 24 hr, except that in liver the first peak of 1.2
      micrograms/g appeared in the 1-hr sample. Tissue-to-plasma concentration ratios
      of centchroman were > 200 times in the lung; > 100 times in the spleen, liver,
      and adipose tissue; and > 40 times in the uterus at maxima in each tissue.
      Similarly, tissue concentrations of DMC were > 350 times in the lung, > 100 times
      in the liver and spleen, and > 25 times in the uterus and adipose tissue than in
      the plasma. High tissue-to-plasma concentration ratios of metabolites than the
      parent drug are indicative of its greater affinity for tissues. Terminal half
      life of the centchroman and DMC in plasma were 24.1 and 36.6 hr, respectively.
      The mean residence time of centchroman was highest in the liver (78.4 hr),
      followed by the uterus (72.7 hr), adipose tissue (47.5 hr), lung (46 hr), spleen
      (44.1 hr), and plasma (37.7 hr). The mean residence time of DMC was also highest
      in the liver (133.7 hr), followed by the uterus (122 hr), adipose tissue (85.2
      hr), lung (62.6 hr), spleen (62.6 hr), and plasma (48.2 hr).

PMID- 8742226
TI  - Absorption, distribution, metabolism, and excretion of N,N-diethyl-M-toluamide in
      the rat.
AB  - This study was conducted to evaluate the pharmacokinetic parameters of
      absorption, distribution, metabolism, and excretion (ADME) of the personal insect
      repellent N,N-diethyl-m-toluamide (DEET) after oral or dermal administration of
      [14C]DEET in the rat. Six experiments were conducted using separate groups, each
      consisting of five male and five female rats. Three experiments involved the
      determination of ADME patterns after oral administration of [14C]DEET as: 1) a
      single low dose (100 mg DEET/kg body weight); 2) a single high dose (500 mg
      DEET/kg body weight); and 3) a repeated low dose (100 mg DEET/kg body weight
      daily for 14 days). A fourth experiment involved the determination of ADME
      patterns after dermal administration of [14C]DEET at a single low dose of 100 mg
      DEET/kg body weight. In these four experiments, urine and feces were collected
      over a 7-day posttreatment period, after which time the animals were euthanized
      and selected tissues and organs were harvested. Urine, feces, and tissues were
      analyzed for total 14C content. The major urinary metabolites were identified,
      and the urinary metabolic profile for each dosage regimen was determined. The
      remaining two experiments examined the distribution of radioactivity in tissues
      of animals euthanized at peak 14C blood levels after receiving a single oral low
      dose or a dermal low dose. In the three experiments designed to determine the
      ADME patterns of DEET after oral administration, 85-91% of the administered
      radioactivity was found in the urine and 3-5% was found in the feces. The overall
      quantitative pattern of excretion of radioactivity into the urine and feces was
      similar for males and females in the three groups; however, the rate at which the
      radioactivity was excreted into the urine differed noticeably between individual
      oral dosing regimens. The fastest rate was observed in the repeated oral low-dose
      group, followed by the single oral low-dose and the single oral high-dose groups.
      In the group of rats that received the dermal low dose, 74-78% of the
      administered dose was found in the urine and 4-7% was found in the feces. An
      additional 6.5% was found on the surface of the skin at the application site or
      in association with the occlusive enclosure. The rate of absorption and
      subsequent excretion of administered radioactivity into the urine and feces was
      much slower after dermal administration than after all oral dosing regimens.
      Total tissue residues of 14C activity at 7 days ranged from 0.15 to 0.67% of the
      administered dose for all dosage regimens. At peak 14C blood levels, the
      percentages of administered dose reaching the systemic circulation and total 14C
      tissue residues were significantly higher in the group of animals administered
      [14C]DEET orally vs. the animals administered [14C]DEET by the dermal route of
      administration. In both cases, the only tissues with 14C residues consistently
      higher than that of plasma were the liver, kidney, and fat. HPLC analysis of
      urine from rats in the ADME phase of the study showed that DEET was metabolized
      completely in all treatment groups, with little or no parent compound excreted in
      the urine. Two major urinary metabolites were identified by mass spectroscopy. In
      both metabolites, the aromatic methyl substituent in the DEET molecule was
      oxidized to a carboxylic acid moiety. One of the metabolites also had undergone N
      dealkylation of an ethyl substituent on the amide moiety.

PMID- 8742227
TI  - Metabolic interactions of putative cytochrome P4503A substrates with alternative
      pathways of dapsone metabolism in human liver microsomes.
AB  - The cytochrome P4503A (CYP3A) subfamily of enzymes are responsible for the
      metabolism of a large number of endogenous and exogenous compounds, and
      activation of some procarcinogens; but the activity is not well understood. N
      Hydroxylation of dapsone in human liver microsomes has been shown to be mediated
      largely by CYP3A4. We have also observed the formation of an as yet unidentified
      metabolite of dapsone, whose formation is inhibited by antibody to CYP3A4, by
      these microsomes. This study investigated the influence of various (22) CYP3A
      putative substrates on the formation of both metabolites of dapsone in human
      liver microsomes. The compounds fall into four different categories on the basis
      of the pattern of their inhibitory interaction with the formation of both
      metabolites: those that inhibited both metabolites; those that inhibited N
      hydroxylamine alone; those that inhibited the unidentified metabolite alone; and
      those with no significant effect on either metabolite. Some others were
      stimulatory. These results are consistent with two alternative but not mutually
      exclusive hypotheses: 1) different isoforms of CYP3A are involved in the
      formation of the alternative metabolites and the pattern of interaction observed
      was caused by the particular isoform(s) that each compound interacted with; or 2)
      formation of the alternative metabolites is a result of dapsone's interaction
      with and orientation at the enzyme's active site and the pattern of interaction
      observed is a consequence of changes in orientation caused by these compounds.
      This study provides relevant observations that must be considered in
      understanding mechanisms of CYP3A-mediated metabolism.

PMID- 8742228
TI  - Pharmacokinetics and metabolism of EXP921, a novel cognitive enhancer, in rats.
AB  - EXP921, 5,5-bis(4-pyridinylmethyl)-5H-cyclopenta[2,1-b:3,4-b']-dipyridine, was a
      potential drug candidate for the improvement of cognitive performance in patients
      with Alzheimer's-type dementia. It has been shown to improve cognitive
      performance in rodent and primate models of learning and memory. To characterize
      the disposition of EXP921, the pharmacokinetics and metabolism of this compound
      were studied in rats after oral and intravenous administrations. EXP921 exhibited
      good bioavailability, 43% at 3 mg/kg and 61% at 10 mg/kg and was rapidly
      eliminated with a terminal half-life ranging from 1.28 to 2.29 hr after oral
      doses. Absorption from oral doses was rapid, as peak plasma levels were reached
      within 1 hr. A major metabolite was identified in plasma as the pyridinyl mono-N
      oxide of EXP921. This metabolite (EXP696) was rapidly formed, and significant
      levels were detected in rat plasma after oral or intravenous administration. Its
      terminal half-life was slightly longer than that of EXP921. EXP696 was found to
      be reduced back to EXP921, demonstrating that the N-oxidation at the pyridyl ring
      is reversible. The interconversion favored the oxidation of EXP921 to EXP696. Two
      additional metabolites were identified in rat plasma at doses higher than or
      equal to 30 mg/kg. They result from despicolylation, followed by hydroxylation in
      the cyclopentane ring.

PMID- 8742229
TI  - Hydroxylation of lauramide diethanolamine by liver microsomes.
AB  - Lauramide diethanolamine (LDEA)--a compound used in cosmetics and soap products
      as an emollient, thickener, and foam stabilizer--was observed to be metabolized
      by rat liver microsomes to two major products that were identified by GC/MS to be
      the 11-hydroxy and 12-hydroxy derivatives of LDEA. The specific activities for
      LDEA 11- and 12-hydroxylation in microsomes prepared from control rats were 2.23
      +/- 0.40 and 0.71 +/- 0.17 nmol/min/mg protein, respectively. Treatment of rats
      with the cytochrome P4504A inducer and peroxisome proliferator, diethylhexyl
      phthalate, increased the LDEA 12-hydroxylation rate to 3.50 +/- 0.48 nmol/min/mg
      protein, a 5-fold increase in specific activity, whereas the LDEA 11-hydroxylase
      activity remained unchanged. Because LDEA contains a 12-carbon side chain, LDEA
      hydroxylation rates were compared with the hydroxylation rates for lauric acid.
      The specific activities of lauric acid 11- and 12-hydroxylation reactions in
      diethylhexyl phthalate-treated rats were 1.7-fold and 3.2-fold greater than the
      LDEA 11- and 12-hydroxylation rates, respectively. When LDEA hydroxylation
      reactions were performed in the presence of a polyclonal antibody to the rat
      P4504A forms, formation of 12-hydroxy-LDEA was inhibited by 80%. Rat kidney
      microsomes also supported the hydroxylation of LDEA at its 11- and 12-carbon
      atoms, with specific activities of 0.05 +/- 0.01 and 0.28 +/- 0.02 nmol/min/mg
      protein, respectively. LDEA was also metabolized to 11- and 12-hydroxy
      derivatives by human liver microsomes at specific activities of 0.22 +/- 0.06 and
      0.84 +/- 0.26 nmol/min/mg protein, respectively.

PMID- 8742230
TI  - In vitro and in vivo biotransformation of 6,7-dimethyl-2,4-di-1-pyrrolidinyl-7H
      pyrrolo[2,3-D]pyrimidine (U-89843) in the rat.
AB  - The biotransformation of 6,7-dimethyl-2,4-di-1-pyrrolidinyl-7H-pyrrolo[2,3
      d]pyrimidine (U-89843) has been studied in rat both in vitro and in vivo. Major
      metabolites observed by HPLC analysis of rat plasma, liver cytosol, and
      microsomal incubations were characterized by UV, LC/MS, and comparison with
      synthetic standards. The structures of the metabolites were shown to be the C-6
      hydroxymethyl (U-97924), C-6 formyl (U-97865), and C-6 carboxyl analogs of U
      89843. In the male rat, formation of U-97924 is mediated by cytochrome P4502C11.
      Kinetic analysis of U-97924 formation indicated that it was a high-affinity/high
      capacity process (KM = 4.2 +/- 0.5 microM; Vmax = 21.2 +/- 0.8 nmol/mg/min).
      Formation of U-97865 via enzymatic oxidation from the primary metabolite U-97924
      was catalyzed by both the microsomal subcellular fraction in a NADPH-dependent
      process (presumably via cytochrome P450) and in cytosol by NAD(+)-dependent
      alcohol dehydrogenase. Upon incubation with cytosolic fractions, U-97865 was
      found to undergo NAD(+)-dependent oxidation, mediated by aldehyde dehydrogenase,
      to the corresponding carboxylic acid. Although significant levels of U-89843, U
      97924, and U-97865 were observed in vivo in rat plasma, only a minor amount of
      the carboxylic acid together with larger amounts of unidentified polar
      metabolites were excreted in urine and feces.

PMID- 8742231
TI  - Involvement of mammalian liver cytosols and aldehyde oxidase in reductive
      metabolism of zonisamide.
AB  - Zonisamide (1,2-benzisoxazole-3-methanesulfonamide), an anticonvulsant agent, is
      primarily metabolized to 2-sulfamoylacetylphenol by reductive cleavage of the 1,2
      benzisoxazole ring. Rabbit liver cytosol with an electron donor of aldehyde
      oxidase exhibited a significant zonisamide reductase activity that was sensitive
      to inhibition by menadione, an inhibitor of aldehyde oxidase. The result
      suggested that the cytosolic activity is caused by aldehyde oxidase, a cytosolic
      enzyme. In fact, rabbit and rat liver aldehyde oxidase had the ability to reduce
      zonisamide when supplemented with its electron donor. Apparent KM and Vmax values
      of aldehyde oxidase for zonisamide were 217 microM and 42 nmol/10 min/mg protein
      in the case of the rabbit liver enzyme, and 542 microM and 382 nmol/10 min/mg
      protein in the case of the rat liver enzyme, respectively. In rabbits, hamsters,
      mice, and guinea pigs, zonisamide reductase activity of the liver cytosols with 2
      hydroxypyrimidine, an electron donor of aldehyde oxidase, was much higher than
      that of the liver microsomes with NADPH. In rats, zonisamide reductase activity
      was examined with liver microsomes and cytosols from seven strains. The 2
      hydroxypyrimidine-dependent cytosolic activity exhibited marked strain
      differences, unlike the NADPH-dependent microsomal activity. 1,2-Benzisoxazole
      was also reduced to salicylaldehyde by rabbit liver cytosol and aldehyde oxidase
      in the presence of 2-hydroxypyrimidine. Stoichiometric studies showed that 2
      sulfamoylacetylphenol was formed accompanying nearly equimolar ammonia from
      zonisamide.

PMID- 8742232
TI  - Modeling the cytochrome P450-mediated metabolism of chlorinated volatile organic
      compounds.
AB  - Comparative molecular field analysis (CoMFA), a three-dimensional quantitative
      structure-activity relationship (3D-QSAR) paradigm, has been used to analyze the
      metabolic rates, as intrinsic clearance, of a series of chlorinated volatile
      organic compounds (VOCs). A comparison between 3D-QSAR and conventional Hansch
      type QSAR is provided. To develop predictive 3D-QSARs for metabolism, the
      standard CoMFA model based on steric and electrostatic potential fields must be
      supplemented with hydropathic and molecular orbital information also in the form
      of three-dimensional fields. A mechanistic interpretation of chlorinated VOC
      metabolism by cytochrome P450 isozymes is provided as a rationalization for the
      inclusion of multiple fields in the CoMFA 3D-QSAR model. Models of this type have
      practical utility in the development of generalized physiologically-based
      pharmacokinetic models, as well as the rational, structure-based, design and/or
      selection of compounds for use in the in vivo and in vitro metabolic studies.

PMID- 8742233
TI  - Comparison of ketoconazole and fluconazole as cytochrome P450 inhibitors. Use of
      steady-state infusion approach to achieve plasma concentration-response
      relationships.
AB  - The ability of two azole antifungal agents, ketoconazole and fluconazole, to
      inhibit hepatic cytochrome P450 activity in vivo in the rat has been determined.
      To make a valid comparison, differences in pharmacokinetic properties between the
      azoles were accounted for by using an infusion approach to maintain steady-state
      plasma concentrations over a range of 1-48 mg/liter. Both compounds showed a
      maximum inhibitory effect, assessed by a reduction in antipyrine clearance, of
      approximately 75%. The relationship between steady-state plasma concentration and
      the degree of inhibition of antipyrine clearance was nonlinear for both azoles.
      However, the inhibitory effect resulted at lower concentrations for ketoconazole
      than for fluconazole. Analysis of these data provided Ki values of 3 and 10
      microM, for ketoconazole and fluconazole, respectively, based on plasma
      concentration of azole. This difference in activity is 2 orders of magnitude
      greater when Ki values are expressed in terms of unbound concentration in the
      blood, which may be more representative of hepatic tissue concentrations. Ki
      values based on unbound drug concentration are 0.07 and 8.7 microM for
      ketoconazole and fluconazole, respectively. These data confirm the conclusions
      based on in vitro findings that ketoconazole is a more inhibitory of mammalian
      cytochrome P450 isoenzymes than fluconazole.

PMID- 8742234
TI  - Local absorption kinetics into the portal system using the portal-venous
      concentration difference after an oral dose of diclofenac in the awakening rat.
      Accelerative effect of bile on intestinal absorption of diclofenac.
AB  - The local absorption kinetics from the intestinal tract into the portal system
      was evaluated using the portal-venous concentration difference (P-V difference)
      after oral administration of diclofenac in conscious rats. The local absorption
      ratio (Fa), mean local absorption time (ta), and relative variance (sigma 2/ta2)
      from the intestinal tract into the portal system were estimated by simultaneously
      measuring the portal and venous concentrations, using diclofenac as a model drug.
      The effect of bile on diclofenac intestinal absorption was also investigated. The
      awakening rats simultaneously cannulated into the jugular and portal veins were
      divided into group A with intact enterohepatic circulation (EHC) and into another
      group with bile-duct cannulation to block EHC. The rats in the latter group were
      further divided into group B without the bile supply to the intestinal tract and
      into group C with the bile supply from the other rat. After oral administration
      of diclofenac to rats in groups A, B, and C, the portal and venous concentrations
      of diclofenac in each rat were simultaneously monitored by HPLC method at proper
      time intervals. The absorption time profile of diclofenac into the portal system
      was directly predicted from P-V difference. Plasma concentrations of diclofenac
      in the portal vein were constantly higher than those in the jugular vein after
      the oral administration. It was demonstrated that P-V difference was caused by
      absorption from the intestinal tract into the portal system. Fa in groups A, B,
      and C were estimated to be 91.5% for 8 hr, 33.8% for 3 hr, and 57.8% for 3 hr,
      respectively. ta in groups A, B, and C were estimated to be 2.26 hr, 0.65 hr, and
      0.96 hr, respectively. sigma 2/ta2 in groups A, B, and C were 1.31, 0.48, and
      0.55, respectively. Fa and ta of diclofenac extensively increased in the presence
      of the bile in the intestinal tract, whereas sigma 2/ta2 was unaffected by the
      bile. The mean absorption time (MAT) almost agreed with ta, which demonstrates
      that the mean transit time through the liver (tH) is negligible in MAT(= ta+tH).

PMID- 8742235
TI  - Biotransformation of lifibrol (U-83860) to mixed glyceride metabolites by rat and
      human hepatocytes in primary culture.
AB  - Lifibrol (U-83860), K12.148) is a lipid-lowering drug that has the potential to
      accumulate in the liver and induce hepatic peroxisome proliferation. To
      investigate the identity and potential human relevance of persistent lifibrol
      related residues in rat liver, rat and human hepatocyte primary cultures were
      treated with 30 microM of [14C]lifibrol. After a steady uptake for 24 hr,
      cellular levels of radioactivity became stable for the next 24-48 hr. A
      nonradioactive lifibrol chase caused an efflux of intracellular radioactivity.
      Cellular autoradiography revealed the association of radioactivity with small
      lipid drops at 6 hr exposure and with large lipid drops at 24 hr exposure. HPLC
      analysis of media revealed that lifibrol acyl glucuronide and a t-butylcarboxylic
      acid metabolite (U-94613) were the major metabolites of rat and human
      hepatocytes, respectively. Using an HPLC method suitable for nonpolar
      metabolites, the analysis of rat and human cell extracts revealed a broad band of
      multiple, radioactive peaks that had a similar retention and UV spectrum to a
      synthetic standard of lifibrol cholesterol ester. Folch extracts of liver from
      rats treated with [14C]lifibrol or unlabeled lifibrol and [14C]acetate had a
      unique radioactive TLC band that had similar HPLC retention to hepatocyte
      residues. The group of nonpolar peaks from the hepatocytes was purified by HPLC.
      Conversion of the lifibrol sec-hydroxy group to a nicotinate ester afforded
      particle beam-electron impact mass spectra of the cholesterol ester standard and
      hepatocyte residues. The derivatized rat hepatocyte residue did not contain
      detectable lifibrol cholesterol ester (M+.816), but did contain molecular ion
      clusters corresponding to a mixed triglyceride of lifibrol and two fatty acids.
      Lifibrol-specific product ions of molecular ion clusters centered at M+.1021,
      1047, and 1073 were observed at m/z 448, 430, and 310. The major lifibrol
      containing triglycerides had a fatty acid composition of C16-C20 with 0-6
      unsaturations.

PMID- 8742236
TI  - Flavonoids, potent inhibitors of the human P-form phenolsulfotransferase.
      Potential role in drug metabolism and chemoprevention.
AB  - The common dietary constituent quercetin was a potent inhibitor of
      sulfoconjugation of acetaminophen and minoxidil by human liver cytosol, partially
      purified P-form phenolsulfotransferase (PST), and recombinant P-form PST, with
      IC50 values of 0.025-0.095 microM. Quercetin inhibition of acetaminophen was
      noncompetitive with respect to acceptor substrate, with a Ki value of 0.067
      microM. A number of other flavonoids, such as fisetin, galangin, myricetin,
      kaempferol, chrysin, and apigenin, were also potent inhibitors of P-form PST
      mediated sulfation, with IC50 values < 1 microM. Studies of structural analogs
      indicated the flavonoid 7-hydroxyl group as particularly important for potent
      inhibition. Potential human metabolites of quercetin were poor inhibitors.
      Curcumin, genistein, and ellagic acid (other polyphenolic natural products) were
      also inhibitors of P-form PST, with IC50 values of 0.38-34.8 microM. Quercetin
      was also shown to inhibit sulfoconjugation by the human hepatoma cell line Hep
      G2. Although less potent in this intact cell system (IC50 2-5 microM), quercetin
      was still more potent than 2,6-dichloro-4-nitrophenol, the classical P-form PST
      inhibitor that has been shown to be an inhibitor also in vivo. These observations
      suggest the potential for clinically important drug interactions, as well as a
      possible role for flavonoids as chemopreventive agents in sulfation-induced
      carcinogenesis.

PMID- 8742237
TI  - 3,3',4,4'-tetrachloroazobenzene absorption, disposition, and metabolism in male
      Fischer 344 rats.
AB  - 3,3',4,4'-Tetrachloroazobenzene (TCAB) is a contaminant generated during the
      synthesis of 3,4-dichloroaniline and 3,4-dichloroaniline-derived pesticides. TCAB
      is isosteric to 2,3,7,8-tetrachlorodibenzo-p-dioxin and has been shown to bind to
      the Ah receptor. Following oral administration of [14C]TCAB (3.2 and 32 mg/kg),
      39-45% of the dosed radioactivity was excreted into the urine and 53-56% was
      recovered in the feces within 48 hr. Less than 6% of the dosed radioactivity
      remained in the tissues examined at 96 hr. After intravenous administration (3.2
      mg/kg), 33% of the dose was excreted in the bile during 6 hr. TCAB metabolites in
      urine were identified using LC/MS. The major metabolites were sulfate ester
      conjugates of hydroxylated mono- or dichloroaniline derivatives. Some of these
      metabolites were also acetylated. After intravenous administration, the
      disappearance of [14C]TCAB from blood was monitored, and the pharmacokinetic
      profile was consistent with a two-compartment model. Pharmacokinetic parameters
      reveal that the compound is readily cleared from the blood with a t1/2 of 4.0 hr,
      clearance of 12.3 ml/min.kg, and an apparent volume of distribution of 4.3
      liters/kg. The absolute oral bioavailability was determined to be 30%. The
      extensive azo reduction of TCAB decreases its systemic absorption after oral
      administration and thereby limits the amount of parent compound available to
      interact with the Ah receptor and decreases the Ah receptor-mediated toxicity.

PMID- 8742238
TI  - Arylamine N-acetyltransferases. Expression in Escherichia coli, purification, and
      substrate specificities of recombinant hamster monomorphic and polymorphic
      isozymes.
AB  - Two isozymes of arylamine N-acetyltransferases (NATs) catalyze the
      biotransformation of arylamines to arylamides, and the bioactivation of
      carcinogenic arylhydroxylamines and arylhydroxamic acids to reactive
      electrophiles capable of forming a variety of DNA and protein adducts. As part of
      a project directed toward delineation of the molecular factors responsible for
      the pronounced differences in the substrate specificity of the isozymes, we have
      recently reported the expression in Escherichia coli and purification of hamster
      NAT1 (NAT1 8) as a fusion protein to an antibody-reactive amino terminus FLAG
      peptide capable of being removed by digestion with enterokinase. Unfortunately,
      the conditions necessary for the removal of the peptide by enterokinase resulted
      in incomplete protease digestion and substantial loss of NAT1 activity.
      Consequently, we have constructed the plasmid pPH8 in which an 11 amino acid
      thrombin proteolysis site has been inserted between the FLAG peptide and the
      amino terminus of NAT1. In addition, a plasmid that expresses hamster NAT2 (NAT2
      15) was constructed by exchanging the gene sequence for NAT1 with the cloned
      sequence for NAT2. Both NAT fusion proteins were expressed in JM105 cells.
      Analysis of catalytically active cell lysates by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis revealed that approximately 30-fold more
      soluble NAT2 was expressed than NAT1 in the bacterial cytosol. The fusion
      proteins were purified to homogeneity by immunoaffinity chromatography, followed
      by gel filtration to remove high molecular weight contaminants. The FLAG peptide
      was subsequently removed by treatment with human thrombin, followed by an
      additional pass over the immunoaffinity column. Unlike the results obtained from
      proteolysis by enterokinase, the activities of the rNAT1 and rNAT2 were shown to
      be unaffected by treatment with thrombin. Moreover, the substrate specificities
      for the recombinant NATs closely matched those observed for NAT1 and NAT2
      isolated from hamster liver.

PMID- 8742239
TI  - Effect of 3-methylcholanthrene on bunitrolol metabolism. Kinetics and
      immunological studies on 4-hydroxylation of bunitrolol catalyzed by two species
      of cytochromes P450 in rat liver microsomes.
AB  - Effect of the induction of cytochrome P4501A1 with 3-methylcholanthrene (3-MC)
      treatment on kinetics of bunitrolol (BTL) 4-hydroxylase activity of rat liver
      microsomes was investigated. The relationship between the rate and BTL
      concentration showed monophasic kinetics (KM = 0.74 +/- 0.13 microM) when
      microsomes from untreated rats were used, whereas microsomes from 3-MC-treated
      rats showed biphasic kinetics (KM1 = 0.76 +/- 0.13, KM2 = 646 +/- 16 microM).
      Anti-cytochrome P450 (P450) BTL (P4502D subfamily) antiserum inhibited the
      reaction > 90% when low concentrations (approximately 10 microM) of BTL were used
      in both microsomes. However, at high BTL concentrations (approximately 2,000
      microM), the inhibition was only up to a half of control in microsomes from 3-MC
      treated rats, whereas in microsomes from untreated rats, the rates were
      suppressed > 90%. Kinetics observed in microsomes from 3-MC-treated rats changed
      to nearly monophasic, with a KM value corresponding to KM2. Anti-P4501A1 IgG, on
      the other hand, hardly inhibited the reaction conducted by liver microsomes from
      3-MC-treated rats when substrate concentrations were low, whereas at higher
      concentrations, it inhibited up to 50%, resulting in a monophasic kinetics with a
      KM value corresponding to KM1. These results clearly indicate that the
      biphasicity of kinetics in BTL metabolism in liver microsomes from 3-MC-treated
      rats is caused by the involvement of two P450 species: P450 BTL and P4501A1 in
      the reaction. This is the first direct evidence to the theoretical hypothesis
      that the biphasic kinetics of the enzyme reaction is caused by the involvement of
      at least two enzymes with different kinetic parameters.

PMID- 8742241
TI  - Pharmacokinetics and biodistribution of 131I-labeled trigalactose conjugate of
      streptavidin.

PMID- 8742240
TI  - Putative active site template model for cytochrome P4502C9 (tolbutamide
      hydroxylase).
AB  - Binding of substrates to the active site of cytochrome P450 enzymes largely
      relies on hydrophobic interactions. However, other binding interactions can take
      place giving the enzyme high regioselectivity and even stereoselectivity. For
      instance, within the major human cytochrome P450s involved in drug metabolism,
      cytochrome P4502D6 (CYP2D6) relies on an ion-pair interaction as a major binding
      factor. There are now a number of substrates reported that have routes of
      metabolism ascribed specifically to cytochrome P4502C9 (CYP2C9), the isoform
      mainly responsible for tolbutamide hydroxylation. Although chemically diverse,
      these substrates have the capability to be hydrogen bond donors (or acceptors).
      The substrate specificity has been rationalized in terms of a hydrogen bond
      donor/acceptor model and, by use of molecular modeling, an active site template
      model for CYP2C9 has been generated. The substrates modeled were phenytoin,
      warfarin, ibuprofen, naproxen, diclofenac, delta 1-tetrahydrocannabinol, 58C80,
      and tolbutamide. In addition to the substrates, the potent, selective inhibitor
      sulfaphenazole was also included in the modeling. An initial hydrogen bond donor
      site (N2) was identified on phenytoin, the most rigid of the substrates.
      Corresponding hydrogen bond donation sites were then identified on all of the
      molecules studied. Using molecular modeling, the site of metabolism and the
      hydrogen bond donation sites of the molecules were then overlaid on phenytoin to
      produce the putative active site model. The resultant model is described by a,
      the distance between the site of metabolism (Y), and the hydrogen bond donor
      heteroatom (X) and C, the angle between this and the hydrogen bond. The mean
      dimensions (+/- SD) for the nine substrates and one inhibitor (a = 6.7 +/- 1.0 A,
      C = 133 +/- 21 degrees) illustrate the degree of overlap achieved.

PMID- 8742242
TI  - Influence of probenecid on the renal excretion mechanisms of cefadroxil.

PMID- 8742244
TI  - Invasion and the pathogenesis of Shigella infections.

PMID- 8742243
TI  - Uptake of enteropathogenic Yersinia by mammalian cells.

PMID- 8742245
TI  - Molecular and cellular bases of Salmonella entry into host cells.

PMID- 8742246
TI  - Molecular and genetic determinants involved in invasion of mammalian cells by
      Listeria monocytogenes.

PMID- 8742247
TI  - Entry of enteropathogenic Escherichia coli into host cells.

PMID- 8742248
TI  - Legionella pneumophila invasion of mononuclear phagocytes.

PMID- 8742249
TI  - A psychophysiological investigation of the selection and the use of partial
      stimulus information in response choice.
AB  - Two alternative explanations were examined for why selective response activation
      sometimes starts before stimulus identification is complete (e.g., J. O. Miller &
      S. A. Hackley, 1992) and sometimes starts only after stimulus identification is
      complete (e.g., R. De Jong, M. Wierda, G. Mulder, & L. J. M. Mulder, 1988).
      Distinct psychophysiological methods related to stimulus identification and
      response selection provided evidence suggesting that partial stimulus information
      is identified but is or is not used before the stimulus is identified more fully,
      depending on task requirements. This result (a) suggests strategic adaptation of
      task performance, (b) is inconsistent with particular discrete and continuous
      models of information processing, and (c) shows the existence of a central
      selection mechanism that can prevent the automatic activation of responses
      associated with preliminary available stimulus information.

PMID- 8742250
TI  - Absence of coactivation in the motor component: evidence from psychophysiological
      measures of target detection.
AB  - Previous research examining response time has supported coactivation under
      certain conditions. Other research has found more forceful responses to redundant
      target than to single-target displays, suggesting coactivation in the motor
      component. The authors tested for motor coactivation using response time,
      response force, and other psychophysiological measures. Experiments 1 and 2
      showed that response force is determined by the number of stimuli, not the number
      of targets, when target-distractor discriminations are required. In Experiment 3,
      1 stimulus was presented on each trial, and the number of target features was
      varied. The response time results showed that coactivation occurred somewhere in
      the information-processing system, but no evidence of motor coactivation was
      found using any psychophysiological measure. These data disconfirm the motor
      coactivation hypothesis for tasks that require visual discriminations.

PMID- 8742251
TI  - Spatial patterns in the control of human arm movement.
AB  - Generalized Procrustes analysis was used to investigate the spatial paths of
      pointing movements. In Experiment 1, 3 participants produced similar spatial
      paths of the hand when repeating a pointing movement many times, despite
      variability in the position and orientation of the movements. The average spatial
      path indicates a fundamental spatial pattern of the motor system, or motor
      primitive. This pattern varied across the workspace. Anterioposterior movements
      were straight, but repeated movements had variable spatial patterns. Lateral
      movements were curved away from the body but had regular spatial patterns.
      Experiment 2 extended these results to movements of different amplitudes in 7
      participants. The motor primitive seems to be abandoned at the end of the
      movement in favor of final adjustments to bring the hand to the target position.
      In Experiment 3, the same participants produced similar motor primitives both
      with and without vision.

PMID- 8742252
TI  - Semantic and spatial components of selective attention.
AB  - Semantic and spatial effects on selective processing were examined. A prime
      presented 250 ms or 1,000 ms before a pair of masked words was related to 1 of
      the words on 1/3 of the trials. Although Experiments 1 and 2 required report of
      both words, processing was selective; typically, just 1 word could be reported.
      In Experiment 1, reported words were more often top words, showing spatial
      selectivity, and more often words related to the prime, showing semantic
      selectivity. Experiment 2 included to-be-ignored peripheral cues 50 ms before the
      pair. Related words were reported more often at both delays, and cuing produced
      an additive benefit at 1,000 ms. Experiment 3 required report of just the cued
      word and included 100-ms cues. Cued words were reported more often, especially at
      1,000 ms and with 100-ms cues, but semantic selectivity also occurred.
      Selectivity via semantic priming and via location reflect separate attentional
      mechanisms.

PMID- 8742253
TI  - Stimulus dimensionality effects in mental rotation.
AB  - Do 3-dimensional (3-D) figures require more time to rotate mentally than do 2
      dimensional (2-D) figures? This question was examined in 2 experiments
      incorporating 15 2-D and 15 3-D stimuli. For 3-D stimuli, block figures were used
      of the type used by R. N. Shepard and J. Metzler in their classic studies. For 2
      D stimuli, block figures were also used, but with all cubes in a single plane,
      resulting in 2-D and 3-D figures matched on surface features. Three-D figures
      elicited steeper slopes than did 2-D figures, supporting the view that the mental
      rotation of visual representations is sensitive to stimulus dimensionality. The
      authors summarize the results of several mental rotation studies that
      investigated stimulus dimensionality and suggest that the evidence across studies
      is consistent with the present finding. They discuss 2 plausible loci for the
      dimensionality effect in S. M. Kosslyn's (1980) theory of mental imagery.

PMID- 8742254
TI  - Temporal and spatial repetition blindness: effects of presentation mode and
      repetition lag on the perception of repeated items.
AB  - In this study, participants were asked to identify briefly presented 5-letter
      (Experiments 1-3) or 2-letter (Experiment 4) strings. Identical items in a
      repeated trial were identified worse than their counterparts in a nonrepeated
      trial, indicating repetition blindness (RB; N. G. Kanwisher, 1987). In Experiment
      1, RB occurred regardless of whether items were presented successively or
      simultaneously. In Experiments 2-4, RB occurred regardless of whether 2
      simultaneously presented items were spatially close or far apart. The magnitude
      of RB, however, varied with presentation mode and repetition lag: RB was smaller
      in simultaneous than successive presentation, and RB increased and then decreased
      with the number of items separating 2 identical ones. These results provide
      important constraints in the interpretation of RB. A model that attributes RB to
      the refractoriness of perceptual recognition units is proposed.

PMID- 8742255
TI  - Display density influences visual search for conjunctions of movement and
      orientation.
AB  - J. Driver and P. McLeod (1992) reported that the ease of visual search for
      targets defined by a conjunction of movement and orientation was affected by an
      interaction between target movement and target-nontarget discriminability. When
      the orientation discrimination to distinguish target from nontarget was
      difficult, stationary targets were easier to find than moving targets. But when
      the orientation discrimination to distinguish target from nontarget was easy,
      moving targets were easier to find than stationary targets. H. J. Muller and J.
      Maxwell (1994) repeated the experiment but failed to find the interaction. The
      authors show that the difference between these results was due to the density of
      the visual displays used. With a high-density display, the authors replicate
      Driver and McLeod's result; with a low-density display, they replicate Muller and
      Maxwell's result.

PMID- 8742256
TI  - Visual search for conjunctions of motion and form: display density and asymmetry
      reversal.
AB  - In visual search for motion-form conjunctions, search rates have been reported to
      be faster for moving than for stationary targets if the target-nontarget
      discrimination is easy (45 degrees target line tilt from vertical), but this
      asymmetry is reversed if the discrimination is difficult (9 degrees tilt) (J.
      Driver & P. McLeod, 1992). Driver and McLeod proposed that gross aspects of form
      discrimination are performed within a motion filter that represents only the
      moving items, whereas fine discriminations rely on a stationary form system that
      is poor at filtering by motion. However, H. J. Muller and J. Maxwell (1994)
      failed to observe the asymmetry reversal, possibly because they used lower
      density displays. The study reported in this article also did not yield an effect
      due to varying display density. This lends support to the notion of a unitary
      form system, with the role of the motion filter being limited to guiding the
      search to the moving items or, if required by the task, the stationary items.

PMID- 8742257
TI  - Perceptual similarity of shapes generated from Fourier descriptors.
AB  - A metric representation of shape is preserved by a Fourier analysis of the
      cumulative angular bend of a shape's contour. Three experiments examined the
      relationship between variation in Fourier descriptors and judgments of perceptual
      shape similarity. Multidimensional scaling of similarity judgments resulted in
      highly ordered solutions for matrices of shapes generated by a Fourier synthesis
      of a few frequencies. Multiple regression analyses indicated that particular
      Fourier components best accounted for the recovered dimensions. In addition,
      variations in the amplitude and the phase of a given frequency, as well as the
      amplitudes of 2 different frequencies, produced independent effects on perceptual
      similarity. These results suggest that a Fourier representation is consistent
      with the perceptual similarity of shapes, at least for the relatively low
      dimensional Fourier shapes considered.

PMID- 8742258
TI  - Phonological variation and inference in lexical access.
AB  - Recent experiments have indicated that lexical access in speech is highly
      intolerant of mismatch. An isolated sequence such as [symbol: see text] strongly
      disrupts access to the underlying lexical entry (wicked). This observation seems
      inconsistent with the systematic variability found in the phonetic form of words.
      Two cross-modal priming experiments tested the hypothesis that phonologically
      regular variation is perceptually acceptable. Participants heard tokens like
      [symbol: see text] embedded in contexts that either licensed the change as a
      result of a regular assimilation process (e.g., [symbol: see text]) or rendered
      the change phonologically unviable (e.g., [symbol: see text]). The tokens with
      contextually unviable deviations did not effectively access lexical
      representations. In contrast, the same tokens in viable phonological context
      primed as strongly as unchanged controls. These results suggest that mapping
      speech onto lexical representations involves on-line phonological inference.

PMID- 8742259
TI  - Distance and distraction effects in the apprehension of spatial relations.
AB  - Theories of the apprehension of spatial relations differ in the predictions they
      make about the effects of distance between the arguments of spatial relations and
      the effects of distracting stimuli presented along with the arguments. One theory
      predicts no effect of distance, another predicts a monotonic increase in reaction
      time (RT) with distance, and a third predicts a monotonic decrease. Most theories
      predict slower RTs but reasonable accuracy when distractors are present, but 1
      theory predicts chance-level accuracy. These predictions were tested in 3
      sentence-picture comparison experiments, in which subjects searched for targets
      exemplifying the relations above and below. Distance had no effect when no
      distractors were present. Distractors slowed RT but did not reduce accuracy to
      chance levels. These results suggest modifications to many of the theories of
      apprehension.

PMID- 8742260
TI  - The visual perception of three-dimensional length.
AB  - A set of 4 experiments evaluated observers' sensitivity to three-dimensional (3
      D) length, using both discrimination and adjustment paradigms with computer
      generated optical patterns and real objects viewed directly in a natural
      environment. Although observers were highly sensitive to small differences in two
      dimensional length for line segments presented in the frontoparallel plane, their
      discrimination thresholds increased by an order of magnitude when the line
      segments were presented at random orientations in 3-D space. There were also
      large failures of constancy, such that the perception of 3-D length varied
      systematically with viewing distance, even under full-cue conditions.

PMID- 8742261
TI  - Exogenous orienting does not reflect an encapsulated set of processes.
AB  - It is widely assumed that orienting attention by the use of exogenous cues
      reflects an encapsulated system impervious to linguistic influence. This view was
      assessed in 4 experiments in which observers made discriminations between target
      characters presented above or below fixation. The spatial location of the target
      was cued by the abrupt onset of a word that was semantically related to a word at
      fixation on half of the trials and unrelated on the remainder. Responses were
      significantly faster when target location was validly cued than when it was not.
      More important, the magnitude of this cuing effect varied as a function of
      whether the abrupt-onset word cue was semantically related to the fixation word.
      These results suggest that linguistic processing influences the process of
      disengagement or movement (or both) from the cued location. Visuospatial
      attention as reflected in the exogenous-cuing paradigm does not depend on an
      encapsulated set of processes.

PMID- 8742262
TI  - Parallel processing in visual short-term memory.
AB  - Visual short-term memory for the contrast and spatial frequency of sinusoidal
      gratings was measured in a delayed discrimination task in which the 2 stimuli to
      be compared were separated in time by 1-10 s interstimulus intervals (ISIs).
      Delayed discrimination thresholds for spatial frequency and contrast were
      compared, both when the 2 types of thresholds were measured in separate blocks of
      trials and when the 2 types of measures were randomly intermixed in an
      uncertainty paradigm, which required participants to process information about
      both dimensions on each trial. In both cases, accuracy of memory for spatial
      frequency was independent of ISI, but memory for contrast decreased as ISI
      increased. Performance was lower in the uncertainty case, but only by an amount
      predicted by statistical decision theory for independent sources. The results are
      consistent with a model assuming a set of parallel special-purpose visual
      discrimination and short-term memory mechanisms.

PMID- 8742263
TI  - Weight perception and the haptic size-weight illusion are functions of the
      inertia tensor.
AB  - The complex effects of mass and volume on weight perception (e.g., the size
      weight illusion) were hypothesized to follow simply from invariants of rotational
      dynamics. In Experiments 1-3, the rotational inertia of wielded, occluded objects
      was varied independently of mass, size, and torque. Perceived heaviness depended
      only on rotational intertia. Reanalysis of J. C. Stevens and L. L. Rubin's (1970)
      study revealed that size's influence on weight perception depends on specific
      patterns of the eigenvalues of the inertia tensor. These patterns were simulated
      in Experiments 4-6 with objects of fixed mass, volume, and visible size.
      Perceived heaviness decreased and increased, respectively, over object sets with
      the eigenvalue patterns of (a) constant mass, increasing volume and (b)
      increasing mass, constant volume. Weight perception and the size-weight illusion
      depend on stimulus invariants, not inference.

PMID- 8742264
TI  - Inattention magnifies perceived length: the attentional receptive field
      hypothesis.
AB  - Five experiments demonstrated that a briefly presented vertical line is judged as
      longer when it is unattended relative to when it is attended. This effect was
      obtained in estimating the length of 1 of 5 possible lines (Experiment 1) and in
      matching the length of a test line to a criterion line (Experiments 3 and 4). The
      directional effect of attention was eliminated when participants estimated the
      length difference between 2 simultaneously presented lines (Experiment 2). An
      additional matching experiment (Experiment 5) demonstrated similar lengthening
      effects for unattended lines and for unattended distances separated by vertically
      displaced dots. It is proposed that the metric for unattended stimuli is composed
      of large attentional receptive fields and that the final output is mediated by
      rounding up processes, so that the unattended line is systematically perceived as
      longer than the attended one.

PMID- 8742265
TI  - Magnitude estimation of perceived odor intensity: empirical and theoretical
      properties.
AB  - Four subjects judged the odor intensities of 7 pyridine concentrations and a
      blank. Computer simulations of a judgment model were compared with the empirical
      data. The model generates data patterns that closely mimic empirical findings.
      The following patterns were confirmed: (a) A power function relates magnitude
      estimates and concentration with an exponent in the range of 0.7 to 1.0 (b) The
      exponent fluctuates so that the level constant is negatively correlated with the
      exponent. (c) The standard deviation of the responses is a negatively accelerated
      function of the mean. (d) The skewness of the responses is relatively high for
      low concentrations and declines toward zero with increasing concentration. (e)
      The correlation between responses to successive stimuli is highest when
      successive concentrations are similar.

PMID- 8742266
TI  - Telling axons where to grow: a role for Eph receptor tyrosine kinases in
      guidance.

PMID- 8742267
TI  - The division of neuronal progenitor cells during migration in the neonatal
      mammalian forebrain.
AB  - In the mammalian forebrain most neurons originate from proliferating cells in the
      ventricular zone lining the lateral ventricles. These neurons become postmitotic
      before they undergo migration to their final destinations. In this study we
      examined the proliferative and migratory properties of cells destined for the
      olfactory bulb that arise postnatally from progenitor cells situated at the
      anterior extent of the subventricular zone (SVZa). The SVZa-derived cells migrate
      along a stereotypical pathway to the olfactory bulb where they become
      interneurons. Using lineage tracers and the cell proliferation marker BrdU, we
      have demonstrated that SVZa-derived cells in the rat retain the capacity for
      division after migrating away from their initial site of generation. These cells
      also express a neuron-specific tubulin, recognized by the antibody TuJ1. These
      results suggest that, unlike other immature neurons, these SVZa-derived cells
      have made a commitment to become neurons before becoming postmitotic.

PMID- 8742268
TI  - Dystonin expression in the developing nervous system predominates in the neurons
      that degenerate in dystonia musculorum mutant mice.
AB  - Dystonia musculorum (dt) is an inherited neurodegenerative disorder in mice. The
      dt gene product, dystonin, contains the bullous pemphigoid antigen 1 coding
      region at its C-terminus and an actin binding domain at its N-terminus. We
      demonstrate that dystonin expression throughout mouse development predominates in
      neurons of the cranial and spinal sensory ganglia. These structures are the most
      severely affected in dystonic mice which could explain their severe sensory
      ataxia. Since we show expression in sensory neurons with small and large
      axoplasmic volumes, but degeneration is restricted primarily to the latter type,
      we suggest that caliber and size of the axon is an important factor in the
      disease process. Dystonin is also expressed in the extrapyramidal motor system
      and in the cerebellum. Functional defects in these cell types could account for
      the dystonic symptoms of dt mice not explained by simple sensory denervation. We
      also detect dystonin expression in motor neurons most of which are unaffected by
      the degenerative process in dt mice.

PMID- 8742269
TI  - NCAM requires a cytoplasmic domain to function as a neurite outgrowth-promoting
      neuronal receptor.
AB  - The neural cell adhesion molecule (NCAM) promotes axonal growth via a homophilic
      binding mechanism by acting both as a neuronal receptor and a substratum ligand.
      We have previously shown that the GPI-linked 120-kDa isoform of NCAM, which lacks
      a cytoplasmic domain, is effective at promoting neurite outgrowth as a cellular
      ligand. To test its ability to function as a neuronal receptor, we have
      transfected PC12 cells with a cDNA encoding human GPI-linked NCAM and tested
      clones displaying stable cell surface expression of this isoform for their
      ability to respond to NCAM in a cellular substratum. Although they continued to
      express endogenous transmembrane rat isoforms of NCAM (140 and 180 kDa), PC12
      cells expressing the GPI-linked NCAM lost their ability to extend neurites in
      response to substratum associated NCAM. However, their outgrowth response to N
      cadherin and other activators of axonal growth was undiminished. Removal of GPI
      linked NCAM from the surface of these clones using phosphatidylinositol-specific
      phospholipase C (PIPLC) fully restored their responsiveness to NCAM, indicating
      that the inhibition was a direct consequence of cell surface expression of this
      "dominant negative" isoform of NCAM. We have previously shown that expression of
      transfected 140- and 180-kDa isoforms of human NCAM in PC12 cells does not result
      in a loss of the neurite outgrowth response to NCAM. However, we show that
      deletion of the cytoplasmic domain of the 140-kDa isoform has the same effect as
      expression of GPI-linked NCAM. We conclude that the cytoplasmic domain of NCAM is
      required for an appropriate neurite outgrowth response.

PMID- 8742270
TI  - Accelerated and widespread neuronal loss occurs in motor neuron degeneration
      (mnd) mice expressing a neurofilament-disrupting transgene.
AB  - To examine the effects of multiple stressors on the onset and specificity of a
      neurodegenerative disease, we derived mnd/mnd mice expressing a neurofilament
      H/lacZ transgene. The mnd mutation causes adult-onset motor dysfunction, and
      produces abnormal ubiquitous accumulation of autofluorescent lipopigment, with
      retinal degeneration and late-onset motor neuron degeneration. The neurofilament
      H-beta-galactosidase fusion protein causes endogenous neurofilament subunits to
      precipitate in perikarya, but shows neither significant neuronal degeneration nor
      behavioral changes until advanced age. In mnd/mnd-transgenic animals,
      neurological symptoms, lipopigment accumulation, and motor neuron loss were
      substantially accelerated. Newly vulnerable populations of neurons also
      degenerated, including cerebellar Purkinje cells and dorsal roots. This study
      exemplifies a synergistic interaction between a neuron-specific and a ubiquitous
      defect, leading to significant neurological consequences. It further indicates
      that cytoskeletal abnormalities similar to those observed in late-onset human
      neurodegenerative disorders can interact with other cellular defects and
      contribute to pathogenesis.

PMID- 8742271
TI  - Early expression of the nerve growth factor receptor ctrkA in chick sympathetic
      and sensory ganglia.
AB  - Avian sympathetic and sensory ganglia are useful models to study the biological
      effects of nerve growth factor (NGF) in vitro as well as in vivo. In order to
      examine the expression pattern of the NGF tyrosine kinase receptor during
      embryogenesis, we cloned a full-length cDNA encoding chick trkA (ctrkA). Compared
      with human trkA, the sequence identity is 46% in the extracellular domain and is
      unevenly distributed between the subdomains. Between embryonic Days 6.5 and 16
      (E6.5 and E16), a single 3-kb ctrkA transcript is detected in sympathetic and
      sensory ganglia, and in situ hybridization experiments reveal the presence of
      ctrkA mRNA in both ganglia from E4.5 onward. The detection of ctrkA in the
      primary sympathetic chain is unexpected in view of previous experiments with
      cultured sympathetic neurons indicating a lack of a survival response to NGF at
      early developmental stages. However, it fits with the observation that, in vivo,
      the administration of NGF markedly affects cell numbers substantially before the
      period of target control of neuronal survival in the sympathetic chain.

PMID- 8742272
TI  - The role of Notch in lateral inhibition and cell fate specification.

PMID- 8742273
TI  - Are we there yet? Management of limb-length inequality.

PMID- 8742274
TI  - Gait asymmetry in patients with limb-length inequality.
AB  - One of the problems facing the clinician is the differentiation between
      functional and structural limb-length inequality. This study investigated 20
      subjects (mean age, 9.0 +/- 3.9 years) with documented limb-length inequalities
      to determine the magnitude of discrepancies that result in gait abnormalities.
      The subjects were asked to walk on an 8-m walkway at a self-selected free pace.
      The contact time, first and second force peaks, and loading and unloading rates
      of the vertical ground-reaction force were measured for both limbs. These
      parameters were predictive for quantification of gait asymmetry. The asymmetry of
      these parameters increased as the limb-length inequality increased. In general, a
      limb-length inequality > 2.0 cm (3.7%) resulted in gait asymmetry that was
      greater than that observed in the normal population. However, the amount of
      asymmetry varied for each individual. A static examination can document an
      anatomic deformity, but this deformity may be compensated for by functional
      adaptations. An analysis of the patient's gait should be performed to identify
      asymmetries during ambulation. Dynamic gait findings, such as demonstrated in
      this study, are needed to support static measurements.

PMID- 8742275
TI  - The effect of femoral lengthening on knee articular cartilage: the role of
      apparatus extension across the joint.
AB  - Loss of joint motion is a common complication of limb lengthening despite newer
      methods of incremental bone elongation. A pilot canine study has demonstrated
      that 30% femoral lengthening causes reproducible knee cartilage injury manifest
      by frank loss of cartilage substance or fibrillation. This study was undertaken
      to examine the potential of knee joint protection by apparatus extension to the
      tibia. Four dogs underwent application of a modified Ilizarov apparatus to the
      femur and tibia with coaxial hinges at the knee. After osteotomy, 30% lengthening
      was undertaken at 0.75 mm daily in three increments. At the completion of
      lengthening, experimental and contralateral knee joints were harvested, assessed
      grossly, decalcified, sagittally sectioned, and stained with safranin-O. All
      control joints were normal histologically. All experimental joints demonstrated a
      decrease in proteoglycan staining without evidence of fibrillation or necrosis.
      These findings suggest a protective effect of the tibial apparatus by avoiding
      joint compression.

PMID- 8742276
TI  - Intraoperative SSEP monitoring during external fixation procedures in the lower
      extremities.
AB  - The efficacy of somatosensory evoked potentials (SSEPs) to detect acute
      peripheral nerve injury during external-fixator application in the lower
      extremities was evaluated in 40 children with 42 Ilizarov surgical procedures.
      The study included patients who were either clinically normal or who had
      preexisting neuropathy but consistent and reliable SSEP responses preoperatively.
      SSEPs were recorded from the popliteal fossa and lumbar regions after alternating
      stimulation of the peroneal and posterior tibial nerves at the ankle. SSEP
      changes due to anesthesia, Ilizarov apparatus application, and other
      intraoperative variables are described. Significant deterioration or total loss
      of SSEP response during surgery occurred in four cases. Two of these patients
      were normal preoperatively and had symptoms of neurologic deficit
      postoperatively; the other two had exacerbations of pre-existing neuropathy. In
      general, the peroneal nerve was at greater risk for injury during surgery. SSEP
      monitoring proved to be technically feasible in external-fixation procedures on
      the lower extremities and may be a practical tool for detection of intraoperative
      nerve compromise.

PMID- 8742277
TI  - Femoral lengthening using the callotasis method: study of the complications in a
      series of 70 cases in children and adolescents.
AB  - The authors reviewed 70 femoral lengthenings performed for limb-length
      discrepancy in 66 children and adolescents using gradual incremental distraction.
      Nine were performed using the Judet lengthener and 61, the Orthofix external
      fixator. Etiology of the femoral shortening was congenital in 22, posttraumatic
      in 17, postinfection in 13, neurologic in 12, and miscellaneous in six. There
      were 83 complications, which were assessed as to their relation to the etiology
      of shortening, amount of lengthening, and age. The incidence of joint
      complications did not seem to be less than that previously encountered with rapid
      distraction methods of lengthening. Bony consolidation was achieved without
      additional surgery in 88% of cases. Delayed consolidation was most commonly
      encountered in children younger than 8 years old with congenitally short femora.
      The authors believe that good results can be obtained by incremental distraction
      by using uniplanar fixation by aggressive physical therapy, proper fixator
      application, and appropriate dynamization of the fixator.

PMID- 8742278
TI  - Results of tibial lengthening with the Ilizarov technique.
AB  - Between June 1987 and June 1992, 62 tibiae in 52 patients underwent lengthening
      by using the Ilizarov technique. Follow-up was from 18 months to 5 years. The
      mean age at surgery was 12.9 years (range, 5-19). The etiology of limb shortening
      was congenital in 53 and acquired in nine tibiae. Thirty-five tibiae had bifocal
      and 27 had unifocal treatment. Twenty-two of the 62 limbs had simultaneous
      treatment of other associated problems, including rotational or angular deformity
      or foot deformity. The average lengthening was 7.5 cm (range, 3.5-12), which was
      equivalent to a 32% average overall increase in limb-segment length (range, 6
      96%). Complications required 28 (22%) unplanned procedures in the 62 tibiae,
      including nine osteotomies for iatrogenic malunion or deformation of regenerate
      bone (31%). Three tendo Achilles lengthenings and posterior ankle capsulotomies
      were required for persistent equinus contractures. Bony complications declined as
      experience with the technique increased. This technique allows simultaneous
      lengthening correction with control of the adjacent foot when required.

PMID- 8742279
TI  - Deficiencies of current methods for the timing of epiphysiodesis.
AB  - A review of 71 epiphysiodeses with adequate orthoroentgenographic and skeletal
      age data was carried out to compare the accuracy of predicting outcome among the
      methods of Anderson and Green, Menelaus, and Moseley. Differing the methodology
      did not have a meaningful effect on their similar but limited accuracy. We
      advocate the use of the Menelaus method, which is simple and based on chronologic
      age, as it proved as accurate as any other method. The routine use of serial
      Gruelich and Pyle skeletal-age data could not be shown to increase the accuracy
      in predicting outcome over serial chronologic-age data, and thus its value in
      limb-length inequality is limited. Regardless of the method used, unpredictable
      results occur in a proportion of patients. The patient and parents should be
      advised of this when planning strategies for limb-length discrepancy.

PMID- 8742280
TI  - Epiphysiodesis of the lower extremity: results of the percutaneous technique.
AB  - The results of 42 percutaneous epiphysiodeses of the lower extremity in 26
      patients are reported. All patients achieved physeal arrest radiographically and
      clinically. No patient developed angular deformity from incomplete arrest. No
      neurovascular complications or fractures occurred. The average hospital stay for
      patients undergoing epiphysiodesis alone was 1 day. Percutaneous epiphysiodesis
      of the lower extremity provides a reliable and safe technique for growth plate
      arrest. The advantages of this technique include a cosmetic scar, short hospital
      stay, low incidence of complications, and reliable physeal arrest.

PMID- 8742281
TI  - Manipulation under anaesthetic of children's fractures: use of the image
      intensifier reduces radiation exposure to patients and theatre personnel.
AB  - During simulated manipulation of children's forearm fractures, levels of
      scattered radiation from both plain radiographs and an image intensifier in
      different modes were measured at various sites on the surgeon, anaesthetist,
      radiographer, and patient both with and without recommended shielding. By using
      fluoroscopy in the pulsed screening mode but allowing only single pulses to
      occur, radiation levels could be substantially reduced to the eye, thyroid, and
      gonads of all those exposed. The radiographer and the anaesthetist were so far
      from the source and guarded by various pieces of equipment that levels were
      almost unrecordable. Effective dose equivalent for the surgeon using pulsed mode,
      based on circa six pulses per manipulation, during 100 manipulations per year,
      would equate to 1 microSv even in the unshielded state (< 0.1 microSv shielded),
      which is approximately 1/1,000 of background radiation at sea level. Because the
      current dose limit is 50 mSv (50,000 microSv) per year for employees, we are many
      orders of magnitude in the safety zone.

PMID- 8742282
TI  - Nitrous oxide compared with intravenous regional anesthesia in pediatric forearm
      fracture manipulation.
AB  - A prospective, randomized study of intravenous (i.v.) regional anesthesia
      compared with nitrous oxide gas was performed in a group of 28 pediatric patients
      with forearm fractures requiring manipulation in the emergency department. The
      groups were compared in terms of pain perceived by the patients, success of
      manipulation, safety, and duration of procedure. The methods showed no
      significant difference in amount of pain perceived by the patient for the total
      pain experience. No medical complication was seen in either group. Because of a
      technical problem with an i.v. regional block, fracture manipulation was not
      completed in one patient. Nitrous oxide treatment required significantly less
      time for completion of the procedure.

PMID- 8742283
TI  - Triplane fracture of the distal radius: case report.
AB  - A 14-year 4-month-old boy sustained a triplane fracture of the distal radius.
      Reduction and maintenance of reduction were achieved by closed manipulation and
      cast. The triplane fracture can occur in areas other than the distal tibia and
      distal humerus and can be successfully treated nonoperatively.

PMID- 8742284
TI  - Traumatic ulnar physeal arrest after distal forearm fractures in children.
AB  - A review of the orthopaedic literature suggests that traumatic ulnar physeal
      arrest associated with radial fracture is a rare occurrence. Twenty-three cases
      of traumatic ulnar physeal arrest have been reported in patients with distal
      radius fractures, and we report five additional cases. A classification system
      for the distal ulnar growth deformities is proposed, and the compensatory radial
      changes are reviewed. Surgical indications for treatment include cosmetic
      deformity, progressive carpal subluxation, and decreased range of motion.
      Surgical options for treatment are discussed and include epiphysiodesis, ulnar
      lengthening, radial osteotomy, and the Suave-Kapandji procedure.

PMID- 8742285
TI  - Occult fracture of the calcaneus in toddlers.
AB  - Five children 14-33 months of age were treated for calcaneal fractures. All had a
      history of trauma with limping or refusal to walk. Physical examination could not
      localize the fracture. Initial radiographs were negative. There were no signs of
      systemic illness. They were treated with long-leg casts. Radiographs after 2
      weeks revealed an arc of sclerosis across the tuberosity of the calcaneus. In no
      case was a bone scan instrumental in making the diagnosis. Awareness of calcaneal
      fractures in the child younger than 36 months can prevent the routine use of bone
      scans to make the diagnosis.

PMID- 8742286
TI  - Ligamentous instability of the knee in children sustaining fractures of the
      femur: a prospective study with knee examination under anesthesia.
AB  - Fifty-five children with 55 fractures of the femur were prospectively studied for
      the presence of ligamentous instability of the knee within 3 weeks from the time
      of injury. Two patients (4%) demonstrated instability on examination under
      anesthesia. A 9-year, 4-month-old boy sustained a second-degree injury to the
      lateral collateral ligament that healed after hip spica cast treatment. The other
      patient, a 12-year, 8-month-old boy, sustained an avulsion fracture of the
      posterior cruciate ligament from the tibial insertion with > 1 cm posterior
      displacement of the tibia on the posterior drawer test. After placement of an
      intramedullary rod, the avulsion fracture was treated with open reduction and
      internal fixation. Although the incidence of ligamentous instability of the knee
      in this study is less than that reported for adults with femur fractures,
      children should nevertheless have a thorough knee examination for ligamentous
      stability as well as radiographic evaluation of the knee.

PMID- 8742287
TI  - Circumferential growth plate fracture of the thoracolumbar spine from child
      abuse.
AB  - We report a unique fracture dislocation of the immature spine associated with
      child abuse and paraplegia. Because it occurs through growth centers, this
      fracture may be initially difficult to identify without special studies. The
      fracture patterns were isolated injuries in both children and were best shown
      with computer tomography. Mechanisms of injury are proposed and should suggest
      child abuse as a cause. Experience with these initial cases has suggested a
      treatment approach based on the mechanism of injury. There is no indirect means
      of reduction for this fracture and anterior open reduction is the treatment of
      choice.

PMID- 8742288
TI  - The posterior approach to the elbow revisited.
AB  - This retrospective study evaluates the clinical results of those patients with
      displaced pediatric elbow fractures who were surgically treated by using a
      modified posterior approach. Twenty patients were evaluated at an average follow
      up time of 17.6 months. At the time of final follow-up, 19 of 20 patients had
      regained full flexion, and 18 of 20 patients had regained full extension. There
      were no angular deformities, loss of strength, late nerve palsies, or cases of
      avascular necrosis. Anatomic reduction is the key in the treatment of displaced
      pediatric elbow fractures. In our experience, the posterior approach to the elbow
      allows exact anatomic reduction, with no resultant angular deformities, and a
      range of motion that is comparable to other reported approaches.

PMID- 8742289
TI  - Subacute hematogenous osteomyelitis: are biopsy and surgery always indicated?
AB  - Forty-four consecutive cases of subacute osteomyelitis admitted at our
      institution over a 12-year period were retrospectively reviewed to assess the
      effectiveness of conservative versus surgical treatment of this condition and to
      determine the indications for open biopsy and surgical debridement. Twenty-four
      cases were treated with antibiotics only, and 20 had surgical debridement
      followed by antibiotics. Except for one case that received inadequate antibiotic
      therapy, all patients responded well to this treatment, whether conservative or
      surgical. At an average follow-up of 18 months, there were no recurrences. Our
      results also showed that with a careful radiologic assessment of these cases,
      most lesions showed characteristic benign radiologic features. We can therefore
      conclude that conservative management of cases of subacute osteomyelitis is as
      effective as surgical treatment. We believe that conservative treatment with
      antibiotics should be the first line of management in most of these cases and
      that open biopsy or surgical debridement or both should be reserved for cases
      that do not respond to antibiotics or show aggressive radiologic features.

PMID- 8742290
TI  - Osteomyelitis of the calcaneus in children.
AB  - Eleven cases of calcaneal osteomyelitis in children are reported. Seven were
      hematogenous cases, and the remaining four were related to puncture wounds. The
      clinical presentation was less dramatic than that seen in typical long bone
      osteomyelitis. Laboratory findings were also less striking. A mixture of
      organisms was isolated from patients in the hematogenous group. In contrast, all
      puncture-related cases had cultures positive for Pseudomonas aeruginosa. Plain
      radiographic findings were noted at the time of presentation in 63%. Those
      findings were characteristically different in hematogenous and puncture-related
      cases. Oblique lateral radiographs can be important for diagnosis in puncture
      related cases. Radionuclide bone scanning was an important diagnostic test in the
      absence of plain radiographic changes and in the very young patient. Surgery was
      performed in 82% of the cases. There were no recurrences or chronic infections.
      Two complications occurred in one patient, including residual scar sensitivity
      and early fusion of the calcaneal apophysis.

PMID- 8742291
TI  - Chondroprotective effect of betamethasone in lapine pyogenic arthritis.
AB  - The chondroprotective effect of betamethasone was examined to determine if
      corticosteroids can decrease articular cartilage injury caused by inflammatory
      exudate in Staphylococcus aureus gonarthritis in rabbits. Three experimental
      groups of antibiotic-treated rabbits were created, comparing parenteral versus
      low-dose intraarticular routes of betamethasone administration. Rabbits that
      received ceftriaxone plus supplemental parenteral betamethasone (group 2)
      demonstrated significantly less articular cartilage proteoglycan loss than did
      rabbits treated with antibiotics alone (group 1). Supplemental intraarticular
      betamethasone (group 3) was somewhat less effective in this regard, possibly
      reflecting the smaller steroid dosage. This animal study introduces histologic
      and biochemical evidence that betamethasone, administered early and in
      conjunction with appropriate systemic antibiotics, may help protect infected
      articular cartilage from proteolytic degradation. Further study is needed to
      prove safety and efficacy of corticosteroids before recommending their clinical
      use in the treatment of septic arthritis.

PMID- 8742292
TI  - Incorporation of cancellous bone into a diaphyseal defect of the radius in
      growing rabbits: tube-shaped versus homogeneous grafts.
AB  - The purpose of the investigation was to find out whether healing of a defect in a
      tubular bone is different when a transplant of crushed spongy bone is tube shaped
      or homogeneous. In rabbits aged 6-8 weeks a defect in the radius was completely
      filled with bone in 34 rabbits. In 91 animals a piece of steel wire, catgut, or
      gelatin sponge was implanted, provoking a tube shape of the crushed bone. The
      animals were killed 8-90 days after the operation. In transverse sections of the
      transplants, the amount of spongy bone, compact bone, and marrow cavity each was
      estimated by means of a grid of squares in the microscope. The remodeling of the
      transplants was considerably faster in the series with tube-shaped grafts than in
      the series in which the whole defect was filled with bone. The material was
      reexamined by histomorphometry. The results confirmed the findings achieved with
      a grid.

PMID- 8742293
TI  - Antley-Bixler syndrome: a disorder characterized by congenital synostosis of the
      elbow joint and the cranial suture.
AB  - The Antley-Bixler syndrome is a rare disorder characterized by craniosynostosis,
      midface hypoplasia, radiohumeral synostosis, joint contractures, arachnodactyly,
      and femoral bowing and fractures. We report four cases with this disorder, all of
      which had craniosynostosis, midface hypoplasia with characteristic facial
      appearance, and contractures of bilateral elbow joints. However, femoral bowing,
      fractures, and arachnodactyly were not seen in our patients. In addition,
      proximal phalanges of the thumb and the great toe showed deformity of the delta
      phalanx in two cases. Characteristic features in these cases were the synostotic
      deformity of the elbow joint; three had radioulnahumeral synostosis, and one had
      radioulnar synostosis. Therefore, our cases indicated that various synostotic
      patterns of the elbow joints may exist in this syndrome. It is reasonable to
      propose that characteristic craniofacial appearance associated with the
      synostosis of the elbow joints of various forms should be considered minimal
      diagnostic criteria of the Antley-Bixler syndrome.

PMID- 8742294
TI  - Pes anserinus syndrome due to solitary tibial spurs and osteochondromas.
AB  - We studied 19 children with the pes anserinus syndrome due to proximal tibial
      exostoses. Nine children had a solitary sessile or pedunculated osteochondroma
      that produced a painful lump that was readily palpable. The symptoms resolved
      following removal of the osteochondroma. Ten children had a bone spur that was
      shaped like a rose thorn. It produced pain with snapping or a feeling of locking
      of the pes anserinus tendons. Careful palpation was required to detect the tender
      bone spur beneath the pes anserinus. In five children, the bone spurs were
      excised because of persistent symptoms, and each was shown to be an exostosis
      without a cartilage cap. The symptoms resolved. However, the bone spurs need not
      be excised if the symptoms improve with rest and do not recur following
      resumption of activities.

PMID- 8742295
TI  - Prophylactic dynamic screw fixation of the asymptomatic hip in slipped capital
      femoral epiphysis.
AB  - Prophylactic dynamic screw fixation (DSF) of clinically and radiographically
      unaffected hips of 34 patients with a contralateral slipped capital femoral
      epiphysis and no evidence of an endocrinopathy or systemic disorder was performed
      using a single cannulated screw. Follow-up ranged from 2 to 12 years (average,
      5.4 years). There was no case of perioperative complication and no avascular
      necrosis or chondrolysis occurred. No preslip or slip became apparent. In all 34
      hips, no tendency toward premature closure of the epiphysis could be observed, no
      growth disturbance including greater trochanteric overgrowth, coxa brevis, or
      coxa vara was noted. This study supports the prophylactic treatment of the
      asymptomatic hip, using a simple and safe fixation method.

PMID- 8742296
TI  - Prediction of reduction in developmental dysplasia of the hip by magnetic
      resonance imaging.
AB  - The acetabular rim of 33 hips in 29 patients with developmental dysplasia of the
      hip was evaluated using magnetic resonance imaging (MRI). The hips were
      classified into the following three groups according to the shape of the
      acetabular rim: 12 hips with sharp acetabular rim (group 1), 13 hips with
      dysplastic and round acetabular rim (group 2), and eight hips with inverted
      acetabular rim (group 3). The position of the femoral head with the hip flexed
      and abducted was also recorded, according to the criteria proposed by Suzuki.
      They were all treated initially with the Pavlik harness. All group 1 hips were
      successfully reduced with the Pavlik harness, whereas in group 2 hips, all but
      three hips were reduced. In all group 3 hips, reduction was not successful. MRI
      provided useful information regarding the probability of reduction with the
      Pavlik harness.

PMID- 8742297
TI  - Spinal anesthesia for spine and lower extremity surgery in infants.
AB  - More premature infants are now surviving because of advances in perinatal care.
      Premature infants often have congenital anomalies requiring operative correction
      and are at increased risk for developing postoperative apnea. The purpose of this
      study was to review our results with spinal anesthesia in infants. Twenty-two
      infants (average age at operation, 11 weeks) had spinal anesthesia for surgery to
      the spine or lower extremities. One patient with bilateral developmental
      dysplasia of the hip had staged operations 1 month apart. Twelve infants (55%)
      were considered to be at increased risk for general anesthesia. The spinal
      anesthetic was 1% tetracaine made hyperbaric with 10% dextrose (tetracaine dose,
      0.5 mg/kg). Spinal anesthesia was successful in all 23 cases. The average follow
      up was 4 years, 1 month, and no complications were attributed to the spinal.
      Spinal anesthesia is a safe and effective substitute for general anesthesia in
      infants having spinal and lower extremity operations and is particularly
      beneficial for high-risk infants.

PMID- 8742298
TI  - Skeletal disorders in children with renal failure.
AB  - There are relatively few reports concerning management of the musculoskeletal
      problems of children with renal failure. From a population group of 124 children
      with renal failure treated at The Children's Hospital, Camperdown, 16 were
      referred for management of skeletal problems. These problems included genu
      valgum, slipped capital femoral epiphysis, ankle valgus, procurvatum of the
      tibia, osteonecrosis, osteochondritis dissecans, "brown tumors," gout, and
      pathological fracture. The methods of management of these problems are discussed.

PMID- 8742299
TI  - NADPH-diaphorase in the developing rat: lower brainstem and cervical spinal cord,
      with special reference to the trigemino-solitary complex.
AB  - A previous study indicated that in adult rat, a distinctive neuronal group in the
      dorsomedial division of the subnucleus oralis of the spinal trigeminal nucleus
      (SpVo) and the rostrolateral part of the nucleus of the solitary tract (Sn) is
      stained for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), and
      suggested that the labeled structures are involved with sensorimotor reflexive
      functions. This study aimed to characterize the developmental expression of NADPH
      d in SpVo and Sn, including other areas of the lower brainstem and cervical
      spinal cord, by means of the enzyme histochemical staining technique, from the
      prenatal through the postnatal period. On embryonic day 12 (E12), no neurons in
      the brain were stained for NADPH-d, whereas blood vessels were stained. Labeling
      in the vessels was consistently present throughout pre- and postnatal periods but
      decreased with development. On E15, labeled neurons appeared in the dorsomedial
      part of SpVo and the rostrolateral part of Sn, but not in the other nuclei. The
      labeled neurons in both nuclei increased in numbers drastically to E17.
      Postnatally, they tended to increase gradually in Sn, but to decrease slightly in
      SpVo. The cell size of labeled neurons reached a plateau at E17 in SpVo, but at
      postnatal day 4 (P4) in Sn. In other nuclei on E17, labeling appeared in the
      lateral paragigantocellular reticular, intermediate reticular, medullary
      reticular, pedunculopontine tegmental, and spinal vestibular nuclei, and laminae
      V, VI, and X of the cervical spinal cord. On E20 and P0, labeling appeared in the
      dorsal column, laterodorsal tegmental, raphe obscurus, parvocellular reticular,
      ventral gigantocellular reticular, and parahypoglossal nuclei, and laminae IX of
      the cervical spinal cord. On P4 labeling appeared in the parabrachial and median
      raphe nuclei, medial and caudolateral Sn, the magnocellular zone of subnucleus
      caudalis of the spinal trigeminal nucleus (SpVc), and laminae III/IV of the
      cervical spinal cord. On P10, labeling appeared in the paratrigeminal and dorsal
      raphe nuclei, the superficial zone of SpVc, and laminae I/II of the cervical
      spinal cord. No newly labeled neurons appeared in any nuclei after P14. The very
      early appearance of NADPH-d staining in SpVo and Sn, which precedes the
      appearance of NADPH-d elsewhere in the brainstem, suggests that the nitric oxide
      (NO)/cyclic guanosine monophosphate (cGMP) system has an important role for
      primitive orofacial sensorimotor reflexive functions. Furthermore, the pattern of
      developmental expression of NADPH-d in SpVo and Sn suggests that the NO/cGMP
      system is organized in a distinct manner in different nuclei.

PMID- 8742300
TI  - Light microscopic localization of calcitonin gene-related peptide in the normal
      feline trigeminal system and following retrogasserian rhizotomy.
AB  - Calcitonin gene-related peptide (CGRP) is a neuropeptide that has been implicated
      in the transmission and modulation of primary afferent nociceptive stimuli. In
      this study, we describe the light microscopic distribution of CGRP
      immunoreactivity (IR) within the feline trigeminal ganglion and trigeminal
      nucleus of normal adult subjects and in subjects 10 and 30 days following
      complete retrogasserian rhizotomy. Within the trigeminal ganglion of normal
      subjects, cell bodies and fibers showed CGRP-IR, whereas immunoreactive fibers
      were rare in the central root region. Within the normal spinal trigeminal and
      main sensory nuclei, CGRP-IR was seen to form a reproducible pattern that varied
      between the different nuclei. Following rhizotomy, most, but not all, of the CGRP
      IR was lost from the spinal trigeminal and main sensory nuclei, except in regions
      where the upper cervical roots and cranial nerves VII, IX and X project into the
      trigeminal nucleus. The pattern seen at 10 days contained more CGRP-IR than that
      seen at 30 days and suggests that degenerating fibers still show CGRP-IR. In
      contrast to the decrease seen in the nuclei after rhizotomy, examination of the
      central root that was still attached to the trigeminal ganglion showed an
      increase in CGRP-IR within fibers, some of which ended in growth conelike
      enlargements. Rhizotomy induced a dramatic increase in CGRP-IR within trigeminal
      motoneurons and their fibers, which was strongest 10 days after rhizotomy and
      weaker at 30 days, which was still stronger than normal. These results indicate
      that the majority of CGRP-IR found in the trigeminal nucleus originates from
      trigeminal primary afferents and that an upregulation of CGRP-IR occurs in
      trigeminal motoneurons and in regenerating fibers in the part of the central root
      that was still attached to the ganglion. In addition, the persistence of CGRP-IR
      fibers in the trigeminal nucleus provides one possible explanation for the
      preservation of pain in humans following trigeminal rhizotomy.

PMID- 8742301
TI  - Relative concentrations and seizure-induced changes in mRNAs encoding three AMPA
      receptor subunits in hippocampus and cortex.
AB  - In situ hybridization was used to determine 1) the relative concentrations of
      mRNAs encoding different subunits of the alpha-amino 3-hydroxy-5-methyl-4-
      isoxazolepropionate receptor family in select regions of rat forebrain and 2)
      whether limbic seizures alter the balances of the subunit mRNAs. GluR1 and GluR2
      mRNA levels were about equal and were much greater than GluR3 mRNA levels in the
      principal neurons of each hippocampal subdivision. Probable interneurons in
      hippocampal molecular layers had much higher levels of GluR1 mRNA than of either
      GluR2 or GluR3 mRNA. Pyramidal cell layers in neo- and paleocortex had a balance
      of mRNAs that was significantly different from the balance in hippocampus: GluR1
      mRNA and GluR3 mRNA levels were about equal and were substantially lower than
      those of GluR2 mRNA. Lesion-induced limbic seizures caused transient changes in
      mRNA levels that were differentiated with regard to subunit and brain region. All
      three mRNAs were decreased in the pyramidal layers of cortex, and changes in
      hippocampal pyramidal cells were smaller. Seizure-induced changes in granule
      cells of the dentate gyrus differed from all other regions examined: GluR1 mRNA
      was reduced to a greater degree than GluR2 mRNA, whereas GluR3 mRNA content was
      markedly increased. These data strongly suggest that the subunit composition of
      alpha-amino 3-hydroxy-5-methyl-4-isoxazolepropionate receptors differs
      significantly between areas of the cortical telencephalon. Furthermore, the data
      indicate that aberrant patterns of physiological activity differentially
      influence the expression of subunit mRNAs in a region-specific and/or cell-type
      specific manner.

PMID- 8742302
TI  - Distribution and synaptology of glossopharyngeal afferent nerve terminals in the
      nucleus of the solitary tract of the hamster.
AB  - The distribution and synaptology of the afferent fibers of the glossopharyngeal
      nerve (IXN) in the hamster were studied by using horseradish peroxidase (HRP)
      histochemistry visualized with light and electron microscopy. Crystals of HRP
      were applied to the trunk of IXN in the vicinity of the petrosal ganglion. The
      densest IXN afferent label was distributed within the nucleus of the solitary
      tract (nst), just caudal to but overlapping with the area of termination of the
      facial nerve. Labeled IXN fibers extended rostrally to the principal trigeminal
      nucleus and caudally to the cervical spinal cord. There was significant labeling
      within the spinal trigeminal complex; the area postrema and the medullary
      reticular formation contained some labeled fibers. Ultrastructurally, the
      synaptic arrangements of anterogradely labeled IXN fibers were examined in the
      nst. Quantitative measures were taken of the area, maximum diameter, perimeter,
      and vesicles of labeled endings and the length of their synaptic junctions with
      dendritic processes. These endings were compared to comparable endings in control
      material and to published descriptions of VIIth nerve afferent terminals in the
      hamster nst. The synaptic relations of IXN afferent endings were predominantly
      with dendritic spines and shafts. The majority (86.6%) of IXN afferent endings
      were with dendritic processes that were not in apparent contact with other,
      unlabeled processes. Only 13.4% of IXN synaptic relationships were with dendritic
      processes that were also contacted by unlabeled vesicle-containing processes.
      This is in contrast to 31.2% of facial nerve afferent endings in the nst which
      make synaptic contact with such processes. There were more direct synaptic
      contacts between facial endings and unlabeled vesicle-containing processes
      (26.1%) than between IXN endings and unlabeled vesicle-containing processes
      (1.3%). Thus, unlike the glomerular-like endings of the gustatory fibers of the
      VIIth nerve, less complex relations appeared to characterize IXN synapses in the
      nst. These differences were related to the differential physiology of gustatory
      fibers in the VIIth nerve and IXN.

PMID- 8742303
TI  - Pattern of selected calcium-binding proteins in the vestibular nuclear complex of
      two rodent species.
AB  - The distribution of immunoreactivity to calbindin, calretinin, and parvalbumin in
      the vestibular nuclear complex and the adjacent nucleus prepositus hypoglossi was
      studied in rats and gerbils. The distribution of stained fibers was the same for
      both rodent species. All three calcium-binding proteins were present in
      vestibular afferents. However, none of the three proteins were present in all
      afferent fibers. Many fibers were labeled in the vestibular nerve and in
      fascicles of the descending vestibular nucleus, as well as ascending fibers in
      the superior vestibular nucleus and fibers directed to the medial vestibular
      nucleus. Labeled terminals were present in the medial vestibular nucleus,
      especially along the ventricular border, in the neuropil of the superior
      vestibular nucleus, and scattered in the descending and ventral portions of the
      lateral vestibular nucleus. Calbindin- and parvalbumin-positive terminals, but
      not calretinin-positive terminals, were present in the neuropil of the dorsal
      lateral vestibular nucleus, especially surrounding the large neuronal somas. Some
      of these terminals are presumably from cerebellar Purkinje cells, which were also
      labeled by both antibodies. The pattern of parvalbumin immunoreactivity was
      slightly different from that of calbindin, indicating that parvalbumin might be
      contained in additional fibers. Some neurons in the vestibular nuclear complex
      were labeled with antibodies to calretinin, but few cells were stained with
      either calbindin or parvalbumin antibodies. The largest group of calretinin
      positive cells was a cluster of small- to medium-sized neurons located in a
      densely stained mesh of dendrites and terminals in the medial vestibular nucleus,
      adjacent to the ventricular border.

PMID- 8742304
TI  - Axonal projection patterns of neurons in the secondary gustatory nucleus of
      channel catfish.
AB  - The second gustatory nucleus of teleost fishes receives ascending fibers from the
      primary gustatory center in the medulla and sends efferent fibers to several
      nuclei in the inferior lobe of the diencephalon. Similar to the corresponding
      parabrachial nucleus in birds and mammals, the secondary gustatory nucleus of
      catfish consists of several cytoarchitectonically distinct subnuclei which
      receive input from different portions of the primary gustatory nuclei. However,
      it is unclear how the subnuclear organization relates to the processing of
      gustatory information in the hindbrain and the subsequent transmission of that
      information to the forebrain. To determine whether cells within different
      subnuclei of the secondary gustatory nucleus of channel catfish project to
      different diencephalic targets, single cells were intracellularly labeled with
      biocytin. Three subnuclei have been identified in the secondary gustatory
      nucleus: a medial subnucleus spanning most of the rostrocaudal extent of the
      nucleus, a central subnucleus and a dorsal subnucleus, the latter two located in
      the rostrolateral portion of the complex. Cells throughout the secondary
      gustatory nucleus typically possessed similar collateral projections to several
      nuclei in the inferior lobe, although four of the six cells filled in the medial
      subnucleus projected only to nucleus centralis. The only apparent subnucleus
      specific projection pattern involved cells at the rostral edge of the secondary
      gustatory nucleus and in the secondary visceral nucleus. Axons of these cells
      terminated only in restricted portions of nucleus lobobulbaris. These results
      suggest that efferents from different subnuclei of the secondary gustatory
      nucleus of catfish, like those of the parabrachial nucleus of birds and mammals,
      do not possess simple, topographical projections to target nuclei in the
      diencephalon.

PMID- 8742305
TI  - Expression of the axonal cell adhesion molecules axonin-1 and Ng-CAM during the
      development of the chick retinotectal system.
AB  - Cell surface glycoproteins expressed on growth cones and axons during brain
      development have been postulated to be involved in the cell-cell interactions
      that guide axons into their target area. Nevertheless, an unequivocal description
      of the mechanism by which such molecules exert control over the pathway of a
      growing axon has not been done. As a crucial requirement in support of a relevant
      involvement of an axonal surface molecule in growth cone guidance, this molecule
      should be expressed in the growth cone. The developing retinotectal system
      provides an excellent opportunity to test whether a particular neuronal surface
      molecule fulfills the requirement of the spatiotemporal coincidence between its
      appearance and the emergence of growth cones because its setup follows the rule
      of chronotopy, i.e., the position of axons in a certain site is determined by the
      time of their arrival. We have analyzed axonin-1 and the neuron-glia cell
      adhesion molecule (Ng-CAM), two axonal surface molecules that promote neurite
      growth in vitro, for their expression in the retina and in the retinotectal
      system of the chick throughout its development. At stage 18, both axonin-like (A
      LI) and Ng-CAM-like immunoreactivity (Ng-CAM-LI) are clearly present in the area
      where first retinal ganglion cells (RGCs) are generated. The immunoreactivity
      spreads synchronously with the formation of RGCs over the developing retina. From
      stage 32 on, the inner plexiform layer is also stained according to its
      temporospatial gradient of maturation. In later stages, the outer plexiform layer
      and the inner segments of photoreceptors also show immunoreactivity. The
      development of A-LI and Ng-CAM-LI along the optic nerve, chiasm, optic tract, and
      in the superficial layers of the optic tectum follows the chronotopic pattern of
      axons, as was found by earlier morphological investigations. Older axons loose
      their A-LI. This allows to localize the position of newly formed axons. The fact
      that A-LI and Ng-CAM-LI parallel the formation and maturation of axons suggests
      that axonin-1 and Ng-CAM may play an important role in the organization of the
      retinotectal system.

PMID- 8742306
TI  - Entorhinal cortex modules of the human brain.
AB  - Much is known about modular organization in the cerebral cortex, but this
      knowledge is skewed markedly toward primary sensory areas, and in fact, it has
      been difficult to demonstrate elsewhere. In this report, we test the hypothesis
      that a unique form of modules exists in the entorhinal area of the human cortex
      (Brodmann's area 28). We examined this issue using classic cyto- and
      myeloarchitectonic stains, immunolabeling for various neurochemicals, and
      histochemistry for certain enzymes. The findings reveal that the entorhinal
      cortex in the human is formed by a mosaic of cellular aggregates whose most
      conspicuous elements are the cell islands of layer II and myelinated fibers
      around the cell islands, the disposition of glutamic acid decarboxylase-positive
      neurons and processes, cytochrome oxidase staining, and the pattern of
      cholinergic afferent fibers. The neuropathology of Alzheimer's disease cases
      highlights the modules, but inversely so, by destroying their features. The
      findings are of interest because 1) anatomically defined modules are shown to be
      present in areas other than the sensory and motor cortices, 2) the modules are
      morphological entities likely to reflect functions of the entorhinal cortex, and
      3) the destruction of entorhinal cortex modules may account disproportionately
      for the severity of memory impairments in Alzheimer's disease.

PMID- 8742307
TI  - Shell and core in monkey and human nucleus accumbens identified with antibodies
      to calbindin-D28k.
AB  - The neurochemical division of the rodent nucleus accumbens into shell and core is
      now a widely accepted concept. However, such divisions in the primate nucleus
      accumbens have yet to be fully clarified and described. In the present study, the
      forebrains of three primates--marmoset, rhesus monkey, and human--and a Wistar
      rat, were immunoreacted with antibodies directed against calbindin-D28k. The
      patterns of immunoreactivity in the primates' ventral striatum were mapped and
      compared to that of rat. Calbindin staining was uneven in all species and there
      was no evidence of a bicompartmental organization, i.e., striosome/patch and
      matrix, in central parts of the nucleus. Nucleus accumbens in primates, as in
      rat, could be divided immunohistochemically into a crescent-shaped outer shell-
      medially, ventrally and laterally--and an inner core. In general, medial parts of
      the shell stained less intensely for calbindin than did lateral parts. However,
      interspecific variation in the intensity of the immunoreactive staining and the
      mediolateral extent of the shell was obvious. The core, which immunostained
      unevenly, was consistently more intensely immunoreactive than either medial or
      lateral shell in all species except the marmoset. These results suggest that the
      neurochemical subdivisions of shell and core established for nucleus accumbens of
      rodents are also present in primates. However, further work is needed to
      establish whether these territories are homologous and, if so, the full extent of
      that homology.

PMID- 8742308
TI  - Direct spinal projections to limbic and striatal areas: anterograde transport
      studies from the upper cervical spinal cord and the cervical enlargement in
      squirrel monkey and rat.
AB  - With the anterograde tracers Phaseolus vulgaris-leucoagglutinin (PHA-L) and
      biotinylated dextranamine (BD), direct spinal connections from the upper cervical
      spinal cord (UC; C1 and C2) and the cervical enlargement (CE; C5-T1) were
      demonstrated in various striatal and limbic nuclei in both squirrel monkey and
      rat. Within each species and from each spinal level, the total number of
      terminals seen in the limbic and striatal areas was approximately 50-80% of the
      number seen within the thalamus. Labeled terminal structures were seen in the
      hypothalamic nuclei, ventral striatum, globus pallidus, amygdala, preoptic area,
      and septal nuclei. In both species, the number of labeled terminals in limbic and
      striatal regions was larger from UC than from CE, although the distributions to
      each nucleus varied with the specific lamina injected. In both species and from
      both UC and CE, approximately one-half of the projections to striatal and limbic
      areas terminated in the hypothalamus. The only region that demonstrated a
      topographical organization was the globus pallidus, where terminals from the CE
      were located dorsomedially to those from the UC. In the rat, UC and CE injections
      into the lateral dorsal horn and pericentral laminae resulted in the largest
      number of limbic and striatal terminations. The proportion of ipsilateral
      terminations was greatest when the medial laminae in the UC or the lateral dorsal
      horn in the CE received injections. Analysis of the morphology of these
      spinohypothalamic and spinotelencephalic terminals showed that, in the squirrel
      monkey, terminals from CE injections were larger than terminals from UC
      injections; no such size difference was evident in the rat. However, limbic and
      striatal terminals in the rat were generally larger than those in the squirrel
      monkey following injections into the UC or CE. The exact function of these direct
      spinal projections to various striatal and limbic areas in primates and in
      rodents remains to be determined. These findings, however, support recent imaging
      studies that suggest that the limbic system plays an important role in the
      mediation of chest pain, perhaps directly through these spinolimbic and
      spinostriatal pathways.

PMID- 8742309
TI  - Laminar and columnar patterns of geniculocortical projections in the cat:
      relationship to cytochrome oxidase.
AB  - We examined the laminar and columnar arrangement of projections from different
      layers of the lateral geniculate nucleus (LGN) to the visual cortex in the cat.
      In light of recent reports that cytochrome oxidase blobs (which in primates
      receive specific geniculate inputs) are also found in the visual cortex of cats,
      the relationship between cytochrome oxidase staining and geniculate inputs in
      this species was studied. Injections of wheat germ agglutinin-conjugated
      horseradish peroxidase were made into the anterior "genu" of the LGN, where
      isoelevation contours of the geniculate layers are distorted due to the curvature
      of the nucleus. Consequently, anterograde labeling from the various LGN layers
      was topographically separated across the surface of the cortex, and labeling in a
      particular isoelevation representation of the cortex could be associated with a
      specific layer of the LGN. Labeling from the A layers, which contain X and Y
      cells, was coextensive with layers 4 and 6 in both area 17 and area 18, as
      previously reported. Labeling from the C layers, which contain Y and W cells,
      occupied a zone extending from the 4a/4b border to part way into layer 3 in area
      17. The labeling extended throughout layer 4 in area 18. There was also labeling
      in layer 5a and layer 1 in both area 17 and area 18. Except in layer 1, labeling
      from the C layers was patchy. In the tangential plane, adjacent sections stained
      for cytochrome oxidase showed that the patches of labeling from the C laminae
      aligned with the cytochrome oxidase blobs. The cytochrome blobs were visible in
      layers 3 and 4a, but not in layer 4b in both areas 17 and 18. These results
      suggest that W cells project specifically to the layer 3 portion of the blobs,
      while Y cells, at least those of the C layers, project specifically to the layer
      4a portion of the blobs in area 17. The heavy synaptic drive of the Y cells is
      probably the cause of the elevated metabolism, and thus, higher cytochrome
      oxidase activity, of the blobs.

PMID- 8742310
TI  - Differential maturation of cholinergic interneurons in the striatal patch versus
      matrix compartments.
AB  - Striatal neurons are generated in two distinct phases. Neurons that become
      postmitotic early in embryonic development come to be located primarily in the
      patch compartment of the striatum, while the majority of the neurons situated in
      the striatal matrix compartment are generated later in embryogenesis. The
      cholinergic interneurons in the striatum, which have been reported to be more or
      less homogeneously distributed in the adult, are all generated early in
      development. Given that early generated neurons are expected to be situated
      primarily in the patch compartment, we investigated the apparently homogeneous
      distribution of cholinergic neurons by analysing their localizations in the patch
      and matrix compartments during striatal development. To selectively mark the
      striatal patch compartment we made injections of the retrograde fluorescent
      tracer True Blue in the substantia nigra on embryonic day 20 or postnatal day
      (P)1, and then stained for cholineacetyltransferase (ChAT) at different time
      points in development. After P7, the distribution of the ChAT positive neurons
      changes from an earlier preference for the patch compartment to a preference for
      an area of the matrix just outside of the patches. Absolute counts show that this
      change in distribution is caused mainly by a late turn on of ChAT by the
      cholinergic neurons in the matrix compartment. These data suggest that there are
      different compartmental subpopulations of cholinergic neurons in the striatum.

PMID- 8742311
TI  - The maximum tolerated dose for inhalation bioassays: toxicity vs overload.

PMID- 8742312
TI  - Is ingested inorganic arsenic a "threshold" carcinogen?
AB  - Ingested inorganic arsenic (As) is known to be a human carcinogen. An intriguing
      question is whether there is a threshold for the carcinogenic effects of As,
      i.e., is there a level below which it does not induce the development of
      cancer(s)? This Roundtable will discuss the United States Environmental
      Protection Agency's As risk assessment using the Taiwan data from different
      viewpoints. It will also consider the hypothesis that there is a threshold for As
      and data for or against this hypothesis. For example, some scientists believe
      that epidemiological data cannot answer this question, while others feel that
      different study designs and larger sampling will provide adequate data. Reasons
      for each position are given. This Roundtable discussion demonstrates the
      controversy surrounding the use of the Taiwan data for risk assessment.

PMID- 8742313
TI  - Variability in gene expression and tumor formation within genetically homogeneous
      animal populations in bioassays.
AB  - Considerable variation in susceptibility to tissue-specific tumor formation in
      response to chronic treatment with low or intermediate dose levels of putative
      carcinogens is observed within populations of genetically homogeneous test
      animals under controlled environmental conditions. Experimental evidence from
      National Toxicology Program studies is reviewed, as are studies of differing
      degrees of carcinogenic response and tumor promotion among iso-and congenic mice
      carrying the Avy (viable yellow) mutation. The data suggest that individual
      variations in carcinogenic response among genetically homogeneous animals may
      derive primarily from differences in regulation of gene transcription.
      Differences in posttranscriptional and posttranslational processing of gene
      products are probably also contributing factors. The viable yellow Avy/a mouse
      model system is uniquely suited for investigating the developmental and molecular
      bases of this phenotypic variability in genetically homogeneous populations since
      various degrees of carcinogenic response and promotion of tumor formation can be
      predicted, a priori, at least as early as 7 days of age by correlation with coat
      color patterns. Ectopic expression of the agouti protein results in enhanced
      susceptibility to tumor formation in tissues which are already sensitized to
      neoplastic transformation by their strain genome. The differences in tumorigenic
      response and coat color pattern among Avy/- mice appear to be associated with
      different DNA methylation states of the promoter of an intracisternal A particle
      inserted into exon 1A of the agouti gene.

PMID- 8742314
TI  - Subchronic toxicity of triethylenetetramine dihydrochloride in B6C3F1 mice and
      F344 rats.
AB  - Triethylenetetramine dihydrochloride (trien-2HCl; CAS No. 38260-01-04), a
      chelating agent used to treat Wilson's disease patients who are intolerant of the
      drug of choice, was tested for subchronic toxicity in B6C3F1 mice and F344 rats.
      Mice and rats received trien-2HCl in the drinking water at concentrations of 0,
      120, 600, or 3000 ppm for up to 92 days. Twenty mice and 18 rats of each sex were
      assigned to each dose group fed either a cereal-based (NIH-31) or a purified (AIN
      76A) diet, both containing nutritionally adequate levels of copper. An additional
      control group of rats and mice received a Cu-deficient AIN-76A diet. This low
      copper diet resulted in Cu-deficiency symptoms, such as anemia, liver periportal
      cytomegaly, pancreatic atrophy and multifocal necrosis, spleen hematopoietic cell
      proliferation, and increased heart weight, together with undetectable levels of
      plasma copper in rats but not in mice. Trien-2HCl lowered plasma copper levels
      some-what (at 600 and 3000 ppm) in rats fed the AIN-76A diet, but did not induce
      the usual signs of copper deficiency. Trien-2HCl caused an increased frequency of
      uterine dilatation at 3000 ppm in rats fed AIN-76A diet that was not noted in
      females fed the Cu-deficient diet. Trien-2HCl toxicity occurred only in mice in
      the highest dose group fed an AIN-76A diet. Increased frequencies of inflammation
      of the lung interstitium and liver periportal fatty infiltration were seen in
      both sexes, and hematopoietic cell proliferation was seen in the spleen of males.
      Kidney and body weights were reduced in males as was the incidence of renal
      cytoplasmic vacuolization. There were no signs of copper deficiency in mice
      exposed to trien-2HCl. The only effect of trien-2HCl in animals fed the NIH-31
      diet was a reduced liver copper level in both rat sexes, noted at 3000 ppm.

PMID- 8742315
TI  - Dose-dependent induction of GST-P+ staining foci by the rat hepatocarcinogen
      methapyrilene in the medium-term bioassay.
AB  - Previous studies have demonstrated that methapyrilene hydrochloride (MP) is a rat
      specific nongenotoxic carcinogen which induces liver tumors in a dose-dependent
      manner following chronic exposure in the diet. This study was conducted to
      determine the dose response of MP in the medium-term bioassay and to compare the
      response to tumor incidence. Two weeks following a single initiating dose of
      diethylnitrosamine (DEN), male F344 rats were administered MP at doses of 0,
      62.5, 125, 250, or 1000 ppm in the diet for 6 weeks. A 2/3 partial hepatectomy
      was performed 3 weeks post-DEN. At termination, sections from the remaining three
      lobes were stained with GST-P antibody. Number and size of foci were measured
      using an image analysis system with a digitizing board. MP induced a dose
      dependent increase in the number of GST-P+ foci/cm2 (0 ppm = 0.85 foci/cm2; 62.5
      ppm = 1.29 foci/cm2; 125 ppm = 1.59 foci/cm2; 250 ppm = 6.55 foci/cm2; 1000 ppm =
      28.23 foci/cm2). A significantly greater number of foci were observed in the
      caudate lobe than in the anterior and posterior lobes. The size of individual
      foci was largely unaffected. This study demonstrates a strong correlation between
      foci induction and tumor incidence and suggests that this assay may have utility
      in predicting dose responses for the chronic bioassay.

PMID- 8742316
TI  - Harmonization of animal clinical pathology testing in toxicity and safety
      studies. The Joint Scientific Committee for International Harmonization of
      Clinical Pathology Testing.
AB  - Ten scientific organizations formed a joint international committee to provide
      expert recommendations for clinical pathology testing of laboratory animal
      species used in regulated toxicity and safety studies. For repeated-dose studies
      in rodent species, clinical pathology testing is necessary at study termination.
      Interim study testing may not be necessary in long-duration studies provided that
      it has been done in short-duration studies using dose levels not substantially
      lower than those used in the long-duration studies. For repeated-dose studies in
      nonrodent species, clinical pathology testing is recommended at study termination
      and at least once at an earlier interval. For studies of 2 to 6 weeks in duration
      in nonrodent species, testing is also recommended within 7 days of initiation of
      dosing, unless it compromises the health of the animals. If a study contains
      recovery groups, clinical pathology testing at study termination is recommended.
      The core hematology tests recommended are total leukocyte (white blood cell)
      count, absolute differential leukocyte count, erythrocyte (red blood cell) count,
      evaluation of red blood cell morphology, platelet (thrombocyte) count, hemoglobin
      concentration, hematocrit (or packed cell volume), mean corpuscular volume, mean
      corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. In the
      absence of automated reticulocyte counting capabilities, blood smears from each
      animal should be prepared for reticulocyte counts. Bone marrow cytology slides
      should be prepared from each animal at termination. Prothrombin time and
      activated partial thromboplastin time (or appropriate alternatives) and platelet
      count are the minimum recommended laboratory tests of hemostasis. The core
      clinical chemistry tests recommended are glucose, urea nitrogen, creatinine,
      total protein, albumin, calculated globulin, calcium, sodium, potassium, total
      cholesterol, and appropriate hepatocellular and hepatobiliary tests. For
      hepatocellular evaluation, measurement of a minimum of two scientifically
      appropriate blood tests is recommended, e.g., alanine aminotransferase, aspartate
      aminotransferase, sorbitol dehydrogenase, glutamate dehydrogenase, or total bile
      acids. For hepatobiliary evaluation, measurement of a minimum of two
      scientifically appropriate blood tests is recommended, e.g., alkaline
      phosphatase, gamma glutamyltransferase, 5' -nucleotidase, total bilirubin, or
      total bile acids. Urinalysis should be conducted at least once during a study.
      For routine urinalysis, an overnight collection (approximately 16 hr) is
      recommended. It is recommended that the core tests should include an assessment
      of urine appearance (color and turbidity), volume, specific gravity or
      osmolality, pH, and either the quantitative or semiquantitative determination of
      total protein and glucose. For carcinogenicity studies, only blood smears should
      be made from unscheduled sacrifices (decedents) and at study termination to aid
      in the identification and differentiation of hematopoietic neoplasia.

PMID- 8742317
TI  - Time course of inhibition of cholinesterase and aliesterase activities, and
      nonprotein sulfhydryl levels following exposure to organophosphorus insecticides
      in mosquitofish (Gambusia affinis).
AB  - Cholinesterase (ChE) in brain and muscle was quickly inhibited during a 48-hr in
      vivo exposure to chlorpyrifos (0.1 ppm), parathion (0.15 ppm), and methyl
      parathion (8 ppm) in mosquitofish (Gambusia affinis). ChE remained inhibited
      during a 96-hr nonexposure period. Brain ChE reached peak inhibition by 12 hr
      after exposure to parathion and chlorpyrifos and by 4 hr after exposure to methyl
      parathion. All insecticides caused greater than 70% ChE inhibition by 4 hr in
      muscle. There was no recovery of ChE after 4 days of nonexposure in either brain
      or muscle. Hepatic aliesterases (AliE) were quickly and greatly inhibited (> 70%
      by 4 hr) after exposure to parathion and chlorpyrifos but not after exposure to
      methyl parathion. Exposure to methyl parathion required 24-36 hr to inhibit
      hepatic AliE to the same level as that following parathion and chlorpyrifos
      exposures at 4 hr. Exposure to all insecticides eventually resulted in greater
      than 80% inhibition of AliE. None of the test groups treated with insecticides
      showed any signs of significant recovery of AliE during the 4 days of
      nonexposure. Nonprotein sulfhydryl (NPSH) concentrations were lower than controls
      after 24 hr of exposure and 96 hr after recovery for all compounds. Exposure to
      methyl parathion lowered NPSH concentrations greater than the other compounds.
      Hepatic AliE appear capable of affording some protection of ChE from inhibition
      following parathion or chlorpyrifos exposures, but considerably less protection
      against methyl parathion.

PMID- 8742318
TI  - Changes in the nasal epithelium of rats exposed by inhalation to mixtures of
      formaldehyde, acetaldehyde, and acrolein.
AB  - Formaldehyde, acetaldehyde, and acrolein are well-known upper respiratory tract
      irritants and occur simultaneously as pollutants in many indoor and outdoor
      environments. The upper respiratory tract, and especially the nose, is the prime
      target for inhaled aldehydes. To study possible additive or interactive effects
      on the nasal epithelium we carried out 1- and 3-day inhalation studies (6 hr/day)
      with formaldehyde (1.0, 3.2, and 6.4 ppm), acetaldehyde (750 and 1500 ppm),
      acrolein (0.25, 0.67, and 1.40 ppm), or mixtures of these aldehydes, using male
      Wistar rats and exposure concentrations varying from clearly nontoxic to toxic.
      The (mixtures of) aldehydes were studied for histopathological and biochemical
      changes in the respiratory and olfactory epithelium of the nose. In addition,
      cell proliferation was determined by incorporation of bromodeoxyuridine and
      proliferating cell nuclear antigen expression. Effects were primarily observed
      after 3 days of exposure. Histopathological changes and cell proliferation of the
      nasal epithelium induced by mixtures of the three aldehydes appeared to be more
      severe and more extensive in both the respiratory and the olfactory part of the
      nose than those observed after exposure to the individual aldehydes at comparable
      exposure levels. As far as nasal histopathological changes and cell proliferation
      are concerned neither dose addition nor potentiating interactions occurred at no
      toxic-effect levels, except for a possible potentiating effect of acetaldehyde at
      noneffect levels. The results did not indicate a major role for aldehyde
      dehydrogenases in the biotransformation of the aldehydes studied. Activities of
      glutathione S-transferase and glutathione reductase after 3 days of exposure to
      acrolein, alone or in combination with formaldehyde and acetaldehyde, were
      depressed whereas the glutathione peroxidase activity was elevated. No decrease
      of nonprotein sulphydryl levels were observed. These findings suggest that, for
      no-toxic-effect levels, combined exposure to these aldehydes with the same target
      organ (nose) and exerting the same type of adverse effect (nasal cytotoxicity),
      but partly with different target sites (different regions of the nasal mucosa),
      is not associated with a greater hazard than that associated with exposure to the
      individual chemicals.

PMID- 8742319
TI  - Subchronic effects of dieldrin and phenobarbital on hepatic DNA synthesis in mice
      and rats.
AB  - Dieldrin, an organochlorine pesticide, has been shown to be hepatocarcinogenic in
      mice but not rats. Phenobarbital, in contrast, induces hepatic tumors in both
      mice and rats. Previous studies have shown that acute dietary exposure of rats or
      mice to either dieldrin or phenobarbital produces several liver changes,
      including centrilobular hypertrophy, induction of hepatic cytochrome P450, and
      increased liver weight. The present study examined the subchronic effect of
      dieldrin (0.1, 1.0, 3.0, 10.0 mg dieldrin/kg diet) and phenobarbital (10, 50,
      100, 500 mg phenobarbital/kg diet) on the induction of hepatic DNA synthesis and
      hepatocyte lethality in male B6C3F1 mice and male F344 rats. Eight-week-old
      animals were treated as above and evaluated for hepatic DNA synthesis after 7,
      14, 21, 28, and 90 days of continual treatment to dieldrin or phenobarbital.
      Maximal induction of hepatic DNA synthesis in mice was seen at the 14-, 21-, and
      28-day sampling times. In rats, no significant increase in hepatic DNA synthesis
      or hepatocyte lethality was observed at any dose of dieldrin investigated.
      Phenobarbital produced a significant increase in hepatic DNA synthesis in both
      rat and mouse liver following 7 days of treatment. The induction of DNA synthesis
      in rat liver was transient, with the labeling index returning to control levels
      by 14 days of treatment. In contrast, mice treated with phenobarbital showed a
      significant increase in hepatic DNA synthesis throughout the treatment. In both
      mice and rats, dieldrin and phenobarbital induced hepatic DNA synthesis
      selectively in the centrilobular region of the hepatic lobule. The lack of an
      increase in serum enzymes indicative of hepatic damage and the absence of liver
      histopathology in mice or rats fed dieldrin or phenobarbital indicate that the
      induction of DNA synthesis was not mediated by a cytolethal, compensatory
      hyperplastic response, suggesting a mitogenic mechanism. Therefore, the species
      specific induction of hepatic DNA synthesis by either dieldrin or phenobarbital
      correlated with the previously observed species-specific induction of hepatic
      cancer by these two compounds.

PMID- 8742320
TI  - Protection against acetaminophen hepatotoxicity by a single dose of clofibrate:
      effects on selective protein arylation and glutathione depletion.
AB  - Previous reports demonstrated that repeated administration of peroxisome
      proliferators protects against acetaminophen (APAP) hepatotoxicity in mice. This
      protection was associated with a decrease in APAP's selective protein arylation
      and glutathione depletion. This study was conducted to determine if a single dose
      of clofibrate (CFB), rather than repeated doses, would similarly prevent APAP
      toxicity. CD-1 male mice received a single dose of 500 mg CFB/kg and controls
      were given corn oil 24 hr prior to APAP challenge. After an 18-hr fast, mice were
      challenged with 800 mg APAP/kg (in 50% propylene glycol) and killed at 4 or 12
      hr. Other mice similarly pretreated were killed without APAP challenge. The
      results showed that pretreatment with a single CFB dose significantly decreased
      APAP-induced hepatotoxicity. At 12 hr after APAP plasma sorbitol dehydrogenase
      activity and the severity of hepatocellular necrosis were decreased in CFB
      pretreated mice. Surprisingly, no differences in hepatic nonprotein sulfhydryl
      (NPSH) depletion or selective arylation of target proteins in cytosol were
      observed at 4 hr after APAP challenge. Neither did a single dose of CFB
      significantly alter hepatic NPSH content prior to APAP challenge. These results
      indicate that protection against APAP hepatotoxicity by CFB does not require
      repeated administration, and the absence of significant alterations in APAP's
      selective protein arylation or glutathione depletion suggests that the protection
      against APAP hepatotoxicity after a single treatment with CFB may differ
      mechanistically from the protection observed after repeated CFB dosing.

PMID- 8742321
TI  - Specific IgE and IgG1 responses to subtilisin Carlsberg (Alcalase) in mice:
      development of an intratracheal exposure model.
AB  - The primary objective of this study was to examine the feasibility of using a
      mouse model to evaluate the immunogenicity of proteins as a potential method to
      determine occupational exposure guidelines. Mice were intratracheally
      administered a benchmark protein allergen, subtilisin Carlsberg (Alcalase) in
      detergent matrix once a week for 4 to 6 weeks and specific IgE and IgG1 levels
      were determined. In all experiments, specific IgE levels were determined by using
      a rat basophilic leukemia cell (RBL) release assay, while specific IgG1 was
      measured by an ELISA. A good correlation was observed between IgE titers
      determined by the RBL assay and rat passive cutaneous anaphylaxis assay.
      Intratracheal administration of protease with detergent matrix was found to
      result in significant IgE and IgG1 responses that were dose related. Detergent
      matrix was found to enhance the Alcalase-specific IgE and IgG1 response when
      administered by the intratracheal route. The IgG1 response was much more robust,
      easier to measure, and found to follow the IgE response. These results suggest
      that a mouse intratracheal model is a feasible approach to examining the
      immunogenic potency of enzymes using specific IgE or IgG1 as the end points.
      Additional development and validation of the mouse model with other types of
      proteins will be pursued.

PMID- 8742322
TI  - Chemopreventive effects of green and black tea on pulmonary and hepatic
      carcinogenesis.
AB  - The chemopreventive effects of decaffeinated green and black tea treatment on
      liver and lung tumorigenesis were examined in carcinogen-treated mice. Male C3H
      mice were given decaffeinated green or decaffeinated black tea in their drinking
      water prior to, during, and after treatment with diethylnitrosamine (50
      micrograms/kg bw, i.p., once per week for 8 weeks). After 40 weeks of tea
      treatment, mice were sampled and examined for pulmonary and hepatic tumors. Mice
      treated with both DENA and tea displayed a significant decrease in the mean
      number of lung and liver tumors compared to DENA-only treated animals. Mice that
      received 0.63 or 1.25% green tea or 1.25% black tea exhibited a reduction in
      liver tumor numbers of 54, 50, and 63%, respectively from that seen in the DENA
      only treated mice. Tea treatment also significantly decreased the multiplicity of
      lung adenomas. Mice receiving DENA and either 0.63 or 1.25% green tea or 1.25%
      black tea showed a decrease in the mean number of lung tumors of 40, 46, and 34%,
      respectively, from DENA-only treated mice. While a possible association between
      the chemopreventive activity of tea on lung tumor response and the concentration
      of (-) epigallocatechin gallate (EGCG) in the tea was suggested, no apparent
      relationship between EGCG concentration and liver tumor response was seen,
      however. These results show a dose-dependent chemoprevention of both lung and
      liver tumors by both black and green tea in diethylnitrosamine-treated C3H mice.

PMID- 8742323
TI  - Evidence of chemical stimulation of hepatic metabolism by an experimental
      acetanilide (FOE 5043) indirectly mediating reductions in circulating thyroid
      hormone levels in the male rat.
AB  - N-(4-Fluorophenyl)-N-(1-methylethyl)-2-[[5-(trifluoromethyl)-1,3, 4-thiadiazol-2
      yl]oxy]acetamide (FOE 5043) is a new acetanilide-type herbicide undergoing
      regulatory testing. Previous work in this laboratory suggested that FOE 5043
      induced reductions in serum thyroxine (T4) levels were mediated via an
      extrathyroidal site of action. The possibility that the alterations in
      circulating T4 levels were due to chemical induction of hepatic thyroid hormone
      metabolism was investigated. Treatment with FOE 5043 at a rate of 1000 ppm as a
      dietary admixture was found to significantly increase the clearance of [125I]T4
      from the serum, suggesting an enhanced excretion of the hormone. In the liver,
      the activity of hepatic uridine glucuronosyl transferase, a major pathway of
      thyroid hormone biotransformation in the rat, increased in a statistically
      significant and dose-dependent manner; conversely, hepatic 5'-monodeiodinase
      activity trended downward with dose. Bile flow as well as the hepatic uptake and
      biliary excretion of [125I]T4 were increased following exposure to FOE 5043.
      Thyroidal function, as measured by the discharge of iodide ion in response to
      perchlorate, and pituitary function, as measured by the capacity of the pituitary
      to secrete thyrotropin in response to an exogenous challenge by hypothalamic
      thyrotropin releasing hormone, were both unchanged from the controlled response.
      These data suggest that the functional status of the thyroid and pituitary glands
      has not been altered by treatment with FOE 5043 and that reductions in
      circulating levels of T4 are being mediated indirectly through an increase in the
      biotransformation and excretion of thyroid hormone in the liver.

PMID- 8742324
TI  - Binding of acrylonitrile to parvalbumin.
AB  - A previous study has shown that acrylonitrile (ACN) has a long half-life in
      rainbow trout muscle and that [14C]ACN appears to be bound to a 10,000-Da protein
      in muscle. The labeled protein was purified from muscle of trout exposed to
      [14C]ACN, separated on 20% SDS-PAGE, and digested for amino acid analysis and
      sequence analysis. These studies indicated that the labeled protein was the
      Ca(2+)-binding protein parvalbumin. Parvalbumin is an important calcium-binding
      protein thought to be involved in the regulation of calcium levels in various
      parts of the body ranging from neurons to fast-twitch muscle contractions. To
      study the reaction between parvalbumin and [14C]ACN, frog parvalbumin was
      incubated with [14C]ACN in vitro under various conditions. These studies
      indicated that the maximum labeling occurred at 1 nmol/nmol parvalbumin and at pH
      7. Amino acid analysis of the labeled protein indicated that the labeled amino
      acid was probably histidine, and endoproteinase Glu-C (V-8) digestion studies
      revealed that the 14C was in the 1-81 amino acid segment of the protein, an area
      that contains two histidines.

PMID- 8742325
TI  - Biopersistence of man-made vitreous fibers and crocidolite asbestos in the rat
      lung following inhalation.
AB  - This study investigated possible relationships between fiber bio-persistence in
      the lung and previously observed differences in pulmonary toxicity between
      asbestos and man-made vitreous fibers (MMVF) following inhalation exposure.
      Fischer 344/N rats were exposed nose only, 6 hr/day for 5 days to 30 mg/m3 MMVF
      (two fiberglass compositions, rock wool, or slag wool) or to 10 mg/m3 crocidolite
      asbestos. At eight time points up to 1 year postexposure, lung fiber burdens were
      analyzed for number/lung and bivariate dimensions using scanning electron
      microscopy (SEM) and for chemical composition using SEM energy dispersive
      spectroscopy. After 365 days, > 95% of long (> 20 microns) MMVFs had disappeared
      from the lung compared to only 17% of long crocidolite fibers. Longer MMVFs
      disappeared more rapidly than short MMVFs, suggesting that long fibers were
      dissolving or breaking. Mean diameters and lengths of the MMVFs decreased with
      time, while the mean diameter of crocidolite remained unchanged and its mean
      length showed an apparent increase, probably related to macrophage-mediated
      clearance of short fibers. Leaching of oxides occurred in the fibrous glasses and
      slag wool and correlated with morphological changes in the fibers over time. No
      chemical or morphological changes were observed in crocidolite fibers. These
      changes in MMVF number, chemistry, and morphology over time in lung tissue
      compared to crocidolite asbestos demonstrate the relatively low biological
      persistence of some MMVFs in the lung and may explain why these MMVFs are not
      tumorigenic in rats, even after chronic exposure at high concentrations.

PMID- 8742326
TI  - Effect of bile duct ligation and unilateral nephrectomy on brain concentration
      and convulsant potential of the quinolone antibacterial agent levofloxacin in
      rats.
AB  - To mimic the excretion route of the quinolone antibacterial agent levofloxacin
      (LVFX) in humans, we produced an excretion-limited (EL) model in male Sprague
      Dawley rats by bile duct ligation and unilateral nephrectomy. We then examined
      the relationship between brain levels of LVFX and its convulsant effects in
      control and EL animals. Serum concentrations of LVFX in EL animals (EL + LVFX)
      were 2.38- and 1.59-fold and brain concentrations were 1.33- and 1.19-fold those
      of the controls (control + LVFX) at 30 min after a single intravenous injection
      of 10 and 100 mg/kg LVFX, respectively. Furthermore EL animals became more
      susceptible to the convulsant effect of LVFX with a 1.28-fold decrease in
      convulsion-inducing dose. In combination with oral pretreatment with 400 mg/kg 4
      biphenylacetic acid (BPAA), convulsion-inducing doses in the control (control +
      LVFX + BPAA) and EL (EL + LVFX + BPAA) groups were markedly decreased by 2.25 and
      9 times that of the control + LVFX group. EL operation and BPAA pretreatment
      slowed the elimination of LVFX in the serum and brain 4 hr later in the following
      order: EL + LVFX + BPAA, control + LVFX + BPAA, EL + LVFX, and control + LVFX
      groups. This order reflects that for the convulsion-inducing doses. These results
      suggest that EL rats may be a useful model for humans and that the convulsant
      effect of LVFX with or without BPAA arises not only from the attainment of
      maximum brain concentration but also from delayed disappearance from the brain.

PMID- 8742327
TI  - Influence of oxygen partial pressure on human and mouse myeloid cell line
      characteristics.
AB  - Mouse and human cells have been reported to have different thiol characteristics
      (J. M. Messina and D. A. Lawrence, 1992, Int. J. Immunopharmacol. 14, 1221-1234).
      In addition, when cells are undergoing active growth, they usually have an
      increased thiol content. In an attempt to determine whether a mouse and a human
      cell line with similar characteristics can be induced to change their phenotype
      simply by being cultured at a lower oxygen partial pressure (pO2), the human KG-1
      and mouse M1 myeloid cell lines were cultured at 5 and 20% oxygen. It is
      important to note that 5% O2 is close to the physiological pO2, whereas the
      percentage of O2 usually employed for most in vitro methods is atmospheric pO2.
      After long-term culturing at 5% (L cell lines) versus 20% O2 (H cell lines), the
      thiol content of the original (H) cell lines significantly changed. The amount of
      total and surface thiols was lower in both L cell lines, but only significantly
      different on the M1 lines, whereas the glutathione content was significantly
      lower in the L cell lines of KG-1 and M1. The mouse lines showed the greatest
      sensitivity to pO2 changes; however, the mouse cell lines were not more sensitive
      to hydrogen peroxide than the human cell lines even though they possess
      significantly less total thiols and glutathione. Interestingly, cell lines
      maintained at lower pO2 (physiological pO2) were more sensitive to hydrogen
      peroxide than their parental counterparts that were maintained at atmospheric
      oxygen levels.

PMID- 8742328
TI  - Absorption and distribution of cadmium in metallothionein-I transgenic mice.
AB  - Metallothionein-I transgenic (MT-TG) mice have higher concentrations of MT in the
      stomach (10x), small intestine (4x), large intestine (6x), liver (15x), and
      kidney (5x) than control mice. The purpose of the present study was to use MT-TG
      mice to determine whether increased concentrations of MT affect cadmium (Cd)
      absorption and distribution. A single dose of 109Cd was given to control and MT
      TG mice orally (0.3-300 mumol/kg, 200 microCi/kg) or intravenously (0.03-10
      mumol/kg, 20 microCi/kg). Cd concentrations in 15 tissues were quantified 7 days
      later. Higher MT concentrations in tissues of MT-TG mice had no appreciable
      effects on the concentration of Cd in tissues compared to controls. An exception
      to this was the MT-TG mice given the highest dose of Cd (300 mumol Cd/kg, po),
      which had twice the tissue Cd concentration of controls. Approximately 60% of the
      Cd administered iv was retained in the tissues; retention of Cd in MT-TG mice was
      similar to that in controls. In both control and MT-TG mice only 0.1-0.3% of Cd
      administered po was retained, except for 1-3% at the higher doses (100 and 300
      mumol/kg). Cd administered iv distributed mainly to the liver (70%) and kidney
      (10%) and was independent of dose. In contrast, when administered po,
      distribution of Cd to the liver increased from 40 to 75% of the dose, whereas
      distribution to kidney decreased from 30 to 7% as doses were increased from 0.3
      to 300 mumol/kg. No difference in pattern of Cd distribution to various organs
      was observed between control and MT-TG mice. These data indicate that higher
      concentrations of MT in MT-TG mice do not appear to inhibit the gastrointestinal
      absorption of Cd nor alter the organ distribution of Cd.

PMID- 8742329
TI  - ATPase activity and molecular chaperone function of the stress70 proteins.
AB  - The codons for the amino acid residues making up the proposed ATP-binding sites
      of the maize (Zea mays L.) endoplasmic reticulum and tomato (Lycopersicon
      esculentum) cytoplasmic Stress70 proteins were deleted from their respective
      cDNAs. The deletions had little effect on the predicted secondary structure
      characteristics of the encoded proteins. Both wild-type and mutant proteins were
      expressed in Escherichia coli and purified to electrophoretic homogeneity. The
      mutant recombinant proteins did not bind to immobilized ATP columns, had no
      detectable ATPase activity, and were unable to function in vitro as molecular
      chaperones. Additionally, the inability to bind ATP was associated with changes
      in the oligomerization state of the Stress70 proteins.

PMID- 8742330
TI  - A wound- and methyl jasmonate-inducible transcript coding for a myrosinase
      associated protein with similarities to an early nodulin.
AB  - Myrosinase is regarded as a defense-related enzyme in the Brassicaceae and is
      capable of hydrolyzing glucosinolates into various compounds, some of which are
      toxic. Several myrosinase isoenzymes exist, and some of them have been found in
      association with nonmyrosinase proteins. One of these associated proteins,
      myrosinase-associated protein (MyAP), was purified from seeds of Brassica napus
      both in complexes with myrosinase and in a free form. MyAP is a glycosylated, 40
      kD protein with at least one intramolecular disufide bridge. A monoclonal anti
      MyAP antibody precipitated myrosinase activity from B. napus seed extracts and in
      these complexes both a 65- and a 70-kD myrosinase were present. The subsequent
      cloning and analysis revealed the existence of a gene family encoding MyAP or
      MyAP-related protein and that transcripts corresponding to MyAP in nonwounded
      plants are found predominantly in seeds. At least some members of the gene family
      exhibited responsiveness toward wounding and methyl jasmonate vapor. MyAP
      displayed considerable similarity to an early nodulin (ENOD8) from Medicago
      sativa and to a proline-rich protein (APG), described as another specific, from
      Arabidopsis thaliana and B. napus. Similarity to expressed sequence tags from
      both A. thaliana and Oryza sativa has also been found.

PMID- 8742331
TI  - Two divergent xyloglucan endotransglycosylases exhibit mutually exclusive
      patterns of expression in nasturtium.
AB  - A cDNA encoding a xyloglucan endotransglycosylase (XET) homolog was isolated from
      nasturtium (Tropaeolum majus) epicotyl RNA. The deduced protein encoded by the
      corresponding gene, termed XET1, was substantially divergent from a previously
      isolated nasturtium XET (NXG1) expressed in germinating seed cotyledons but was
      highly homologous to XET genes isolated from vegetative tissues of several
      distantly related species. XET1 was expressed at the level of mRNA accumulation
      in all vegetative tissues examined (root, epicotyl, stem, and leaf) except in
      germinating cotyledons. Conversely, NXG1 exhibited the opposite pattern of
      expression and its mRNA was detected exclusively in cotyledons. Both XET1 and
      NXG1 were apparently encoded by single genes. Protein extracts from epicotyls or
      germinating cotyledons, in which XET1 or NXG1 are specifically expressed
      respectively, exhibited XET activity when assayed using two different xyloglucan
      substrates. XET activity from epicotyl extracts used nonfucosylated seed amyloid
      xyloglucan or fucosylated stem xyloglucan as a substrate with equal facility,
      whereas XET activity from cotyledon extracts had a significantly higher activity
      against nonfucosylated xyloglucan. The existence in a single species of two XETs
      possessing divergent amino acid sequences, mutually exclusive patterns of
      expression, and potentially different activities against xyloglucan substrates
      demonstrates the existence of different classes of XET and suggests differing
      roles in vivo.

PMID- 8742332
TI  - Molecular cloning, immunochemical localization to the vacuole, and expression in
      transgenic yeast and tobacco of a putative sugar transporter from sugar beet.
AB  - Several plant genes have been cloned that encode members of the sugar transporter
      subgroup of the major facilitator superfamily of transporters. Here we report the
      cloning, expression, and membrane localization of one of these porters found in
      sugar beet (Beta vulgaris L.). This clone, cDNA-1, codes for a protein with 490
      amino acids and an estimated molecular mass of 54 kD. The predicted membrane
      topology and sequence homology suggest that cDNA-1 is a member of the sugar
      transporter family. RNA gel blot analysis revealed that this putative sugar
      transporter is expressed in all vegetative tissues and expression increases with
      development in leaves. DNA gel blot analysis indicated that multiple gene copies
      exist for this putative sugar transporter in the sugar beet genome. Antibodies
      directed against small peptides representing the N- and C-terminal domains of the
      cDNA1 protein identified a 40-kD polypeptide in microsomes isolated from cDNA-1
      transformed yeast (Saccharomyces cerevisiae). Moreover, the same protein was
      identified in sugar beet and transgenic tobacco (Nicotaina tobacum L.) membrane
      fractions. Detailed analysis of the transporter's distribution across linear
      sucrose gradients and flotation centrifugations showed that it co-migrates with
      tonoplast membrane markers. We conclude that this carrier is located on the
      tonoplast membrane and that it may mediate sugar partitioning between the vacuole
      and cytoplasmic compartments.

PMID- 8742333
TI  - The correlation between heat-shock protein accumulation and persistence and
      chilling tolerance in tomato fruit.
AB  - Heating tomato fruit (Lycoperiscon esculentum) for 48 h at 38 degrees C prevented
      chilling injury from developing after 21 d at 2 degrees C, whereas unheated fruit
      developed high levels of injury. Although the overall protein pattern as seen by
      Coomassie blue staining was similar from heated and unheated fruit, some high-
      and many low-molecular-mass proteins were observed in the heated fruit that were
      absent or present in reduced amounts in unheated fruit. When fruit wer injected
      with [35S]methionine at harvest and then heated, they accumulated high levels of
      specific radiolabeled proteins that could still be detected after 21 d at 2
      degrees C. If the fruit were held at 20 degrees C after heating, the label in the
      proteins declined rapidly and these fruit were also sensitive to chilling injury.
      Hsp70 antibody reacted more strongly with proteins from heated and chilled fruit
      than with proteins from chilled fruit. Hsp18.1 antibody reacted strongly with
      proteins from heated fruit but not with those from unheated fruit. A 23-kD
      protein, highly labeled in heated fruit but not in unheated fruit, had its amino
      terminus sequenced. To our knowledge, this is the first report showing a
      relationship between the persistence of heat-shock proteins and chilling
      tolerance in a plant tissue.

PMID- 8742334
TI  - Molecular cloning and photoperiod-regulated expression of gibberellin 20-oxidase
      from the long-day plant spinach.
AB  - Spinach (Spinacia oleracea L.) is a long-day (LD) rosette plant in which stem
      growth under LD conditions is mediated by gibberellins (GAs). Major control
      points in spinach are the later steps of sequential oxidation and elimination of
      C-20 of C20-GAs. Degenerate oligonucleotide primers were used to obtain a
      polymerase chain reaction product from spinach genomic DNA that has a high
      homology with GA 20-oxidase cDNAs from Cucurbita maxima L. and Arabidopsis
      thaliana Heynh. This polymerase chain reaction product was used as a probe to
      isolate a full-length cDNA clone with an open reading frame encoding a putative
      43-kD protein of 374 amino acid residues. When this cDNA clone was expressed in
      Escherichia coli, the fusion protein catalyzed the biosynthetic sequence GA53-
      >GA44-->GA19-->GA20 and GA19-->GA17. This establishes that in spinach a single
      protein catalyzes the oxidation and elimination of C-20. Transfer of spinach
      plants from short day (SD) to LD conditions caused an increase in the level of
      all GAs of the early-13-hydroxylation pathway, except GA53, with GA20, GA1, and
      GA8 showing the largest increases. Northern blot analysis indicated that the
      level of GA 20-oxidase mRNA was higher in plants in LD than in SD conditions,
      with highest level of expression in the shoot tips and elongating stems. This
      expression pattern of GA 20-oxidase is consistent with the different levels of
      GA20, GA1, and GA8 found in spinach plants grown in SD and LD conditions.

PMID- 8742335
TI  - Ascorbate peroxidase. A prominent membrane protein in oilseed glyoxysomes.
AB  - The glyoxysomes of growing oilseed seedlings produce H2O2, a reactive oxygen
      species, during the beta-oxidation of lipids stored in the cotyledons. An
      expression library of dark-grown cotton (Gossypium hirsutm L.) cotyledons was
      screened with antibodies that recognized a 31-kD glyoxysomal membrane
      polypeptide. A full-length cDNA clone (1258 bp) was isolated that encodes a 32-kD
      subunit of ascorbate peroxidase (APX) with a single, putative membrane-spanning
      region near the C-terminal end of the polypeptide. Internal amino acid sequence
      analysis of the cotton 31-kD polypeptide verified that this clone encoded this
      protein. This enzyme, designated gmAPX, was immunocytochemically and
      enzymatically localized to the glyoxysomal membrane in cotton cotyledons. The
      activity of monodehydroascorbate reductase, a protein that reduces
      monodehydroascorbate to ascorbate with NADH, also was detected in these
      membranes. The co-localization of gmAPX and monodehydroascorbate reductase within
      the glyoxysomal membrane likely reflects an essential pathway for scavenging
      reactive oxygen species and also provides a mechanism to regenerate NAD+ for the
      continued operation of the glyoxylate cycle and beta-oxidation of fatty acids.
      Immunological cross-reactivity of 30- to 32-kD proteins in glyoxysomal membranes
      of cucumber, sunflower, castor bean, and cotton indicate that gmAPX is common
      among oilseed species.

PMID- 8742336
TI  - Polyembryony in Citrus. Accumulation of seed storage proteins in seeds and in
      embryos cultured in vitro.
AB  - Citrus exhibits polyembryonic seed development, an apomictic process in which
      many maternally derived embryos arise from the nucellus surrounding the
      developing zygotic embryo. Citrus seed storage proteins were used as markers to
      compare embryogenesis in developing seeds and somatic embryogenesis in vitro. The
      salt-soluble, globulin protein fraction (designated citrin) was purified from
      Citrus sinensis cv Valencia seeds. Citrins separated into two subunits averaging
      22 and 33 kD under denaturing sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. A cDNA clone was isolated representing a citrin gene expressed
      in seeds when the majority of embryos were at the early globular stage of embryo
      development. The predicted protein sequence was most related to the globulin seed
      storage proteins of pumpkin and cotton. Accumulation of 33-kD polypeptides was
      first detected in polyembryonic Valencia seeds when the majority of embryos were
      at the globular stage of development. Somatic Citrus embryos cultured in vivo
      were observed to initiate 33-kD polypeptide accumulation later in embryo
      development but accumulated these peptides at only 10 to 20% of the level
      observed in polyembryonic seeds. Therefore, factors within the seed environment
      must influence the higher quantitative levels of citrin accumulation in nucellar
      embryos developing in vivo, even though nucellar embryos, like somatic embryos,
      are not derived from fertilization events.

PMID- 8742337
TI  - Purification and characterization of an oat fructan exohydrolase that
      preferentially hydrolyzes beta-2,6-fructans.
AB  - Oat (Avena sativa cv Fulghum) fructan hydrolase was purified by ammonium sulfate
      precipitation and anion-exchange, hydrophobic interaction, and size-exclusion
      chromatography. The enzyme was purified to homogeneity as determined by the
      presence of a single band (43 kD) on a silver-stained sodium dodecyl sulfate
      polyacrylamide gel. A mixture of beta-2,6-linked fructan (neokestin) isolated
      from oat was used as the substrate to purify fructan hydrolase. Neokestin and
      small degree of polymerization fructan isomers were used to characterize the
      substrate specificity of the purified enzyme. The purified fructan hydrolase
      catalyzed hydrolysis of the terminal beta-2,6 linkage of 6G,6-kestotetraose 3.5
      times more rapidly than it hydrolyzed the terminal beta-2,6 linkage of 6G
      kestotriose and approximately 10 times faster than it hydrolyzed the terminal
      beta-2,1 linkage of chicory inulin. Sucrose and 1-kestose were not substrates.
      The Km for neokestin (beta-2,6-linked fructans with a degree of polymerization of
      7-14) hydrolysis was 2.8% (w/v), and the Vmax was 0.041 mumol min-1 mL-1. The Km
      for hydrolysis of 6G,6-kestotetraose was 5.6% (w/v), and the Vmax was 0.138 mumol
      min-1 mL-1. Catalysis was exolytic and by multiple chain attack. Hydrolysis of
      neokestin was maximal at pH 4.5 to 5.0.

PMID- 8742338
TI  - Light suppresses 3-Hydroxy-3-methylglutaryl coenzyme A reductase gene expression
      in Arabidopsis thaliana.
AB  - 3-Hydroxy-3-methylglutaryl (HMG) coenzyme A reductase mRNA accumulates
      preferentially in dark-grown Arabidopsis plants. As one step toward understanding
      the role that light plays in the regulation of the mevalonate pathway in plants,
      we characterized the suppression of HMG1 gene expression in response to
      illumination wavelength, duration, and fluence rate. The accumulation of HMG1
      mRNA by dark treatment is suppressed by continuous exposure to white light and is
      dependent on the amount of light perceived during the period of illumination. By
      using promoter/reporter gene fusions we also demonstrate that this reaction is
      mediated by cis-acting elements that reside in the Arabidopsis HMG1 promoter and,
      therefore, is likely to be controlled at the transcriptional level. HMG1
      expression is differentially responsive to continuous blue and red light but not
      to far-red light. In contrast, changes in HMG1 mRNA levels were not observed in
      response to brief light pulses of any spectrum, suggesting that continuous
      illumination is required for sustained and maximal suppression of HMG coenzyme A
      reductase expression. Taken together, these data indicate that light-mediated
      control of the HMG1 gene is mediated by a regulatory circuit that monitors
      aspects of both spectral quality and fluence and involves either multiple
      photoreceptors or a single photoreceptor that is differentially sensitive to both
      blue and red light.

PMID- 8742339
TI  - Purification of a Zn-binding phloem protein with sequence identity to chitin
      binding proteins.
AB  - In citrus blight, a decline disorder of unknown etiology, the tree canopy
      exhibits symptoms of Zn deficiency while Zn accumulates in the trunk phloem. We
      have purified a Zn-binding protein (ZBP) from phloem tissue of healthy and blight
      affected citrus (Citrus sinensis [L.] Osbeck on Citrus jambhiri [L.]). The
      molecular weight of the ZBP was estimated to be 5000 by size-exclusion
      chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Ion
      exchange chromatography at pH 8.0 demonstrated the 5-kD ZBP to be anionic. A
      partial N-terminal amino acid sequence revealed a cysteine-, glycine-rich domain
      with 45 to 80% identity with the chitin-binding domain of hevein, wheat germ
      agglutinin, and several class I chitinases. That the abundance of this protein
      increased 2.5-fold in association with Zn accumulation in the phloem is
      characteristic of citrus blight. Tissue mass changes of the phloem suggests that
      altered tissue structure accompanies blight. Phloem accumulation of the 5-kD ZBP
      may be in response to wounding or other stress of blight-affected citrus.

PMID- 8742340
TI  - alpha-L-fucosyltransferases from radish primary roots.
AB  - A novel alpha-L-fucosyltransferase capable of transferring L-fucose (L-Fuc) from
      GDP-L-Fuc to the O-2 of alpha-L-arabinofuranosyl residue (GDP-L-Fuc:alpha-L
      arabinofuranoside 2-alpha-L-fucosyltransferase) has been found in the microsomal
      fraction of primary roots from 6-d-old radish (Raphanus sativus L.) seedlings.
      Enzyme activity was measured fluorometrically at 25 degrees C using a
      pyridylaminated trisaccharide, L-arabinofuranosylf alpha(1-->3)D-galactopyranosyl
      beta(1-->6)D-galactose (AraGalGal-PA) as the acceptor. This enzyme found in the
      microsomal fraction is maximally active at pH 6.8 and requires 0.1% (w/v)
      Zwittergent 3-16 and 5 mM Mn2+. Chemical and enzymatic analyses of fucosylated
      AraGalGal-PA confirmed the attachment of L-Fuc to the L-arabinofuranosyl (L-Araf)
      residue at O-2 by alpha-glycosidic linkage. Radiolabeling was used to assay L-Fuc
      transfer to L-Araf-containing galacto-oligomers and tamarind xyloglucan. The
      enzyme specific for the L-Araf residue undergoes development- and organ-specific
      expression in root tissue, whereas the L-Fuc transfer to tamarind xyloglucan can
      be detected in microsomal fractions from various organs in developing radish
      plants. Enzyme assays of membranes fractionated from microsomal fractions
      revealed that two distinct alpha-L-fucosyltransferases with different acceptor
      specificity are associated with Golgi membranes from primary roots, whereas
      hypocotyl Golgi membranes completely lack the enzyme specific for the L-Araf
      residue.

PMID- 8742342
TI  - The electronic Plant Gene Register.

PMID- 8742341
TI  - Violaxanthin de-epoxidase.
AB  - Violaxanthin de-epoxidase catalyzes the de-epoxidation of violaxanthin to
      antheraxanthin and zeaxanthin in the xanthophyll cycle. Its activity is optimal
      at approximately pH 5.2 and requires ascorbate. In conjunction with the
      transthylakoid pH gradient, the formation of antheraxanthin and zeaxanthin
      reduces the photochemical efficiency of photosystem II by increasing the
      nonradiative (heat) dissipation of energy in the antennae. Previously,
      violaxanthin de-epoxidase had been partially purified. Here we report its
      purification from lettuce (Lactuca sativa var Romaine) to one major polypeptide
      fraction, detectable by two-dimensional isoelectic focusing/sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, using anion-exchange chromatography
      on Mono Q and a novel lipid-affinity precipitation step with
      monogalactosyldiacylglyceride. The association of violaxanthin de-epoxidase and
      monogalactosyldiacyglyceride at pH 5.2 is apparently specific, since little
      enzyme was precipitated by eight other lipids tested. Violaxanthin de-epoxidase
      has an isoelectric point of 5.4 and an apparent molecular mass of 43 kD. Partial
      amino acid sequences of the N terminus and tryptic fragments are reported. The
      peptide sequences are unique in the GenBank data base and suggest that
      violaxanthin de-epoxidase is nuclear encoded, similar to other chloroplast
      proteins localized in the lumen.

PMID- 8742343
TI  - A good and peaceful death: a personal statement.

PMID- 8742344
TI  - Ethical issues in suicide, assisted suicide, and euthanasia.

PMID- 8742345
TI  - Religious reflections on suicide, assisted suicide and euthanasia.

PMID- 8742346
TI  - South Carolina law and physician assisted suicide.

PMID- 8742347
TI  - Ethical arguments against physician assisted death.

PMID- 8742348
TI  - Ethical arguments in favor of physician assisted death.

PMID- 8742349
TI  - Decisions concerning the end of life: a political and ethical view of euthanasia
      in The Netherlands.

PMID- 8742350
TI  - Revisiting assisted death and euthanasia. Report of the SCMA Medical Ethics
      Committee.

PMID- 8742352
TI  - Facing death.

PMID- 8742351
TI  - Assisted dying in South Carolina: a family divided.

PMID- 8742353
TI  - Assessment of the biodegradation potential of psychrotrophic microorganisms.
AB  - Bioremediation of polluted temperate and cold temperature environments may
      require the activity of psychrotrophic bacteria, because their low temperature
      growth range parallels the ambient temperatures encountered in these
      environments. In the present study, 135 psychrotrophic microorganisms isolated
      from a variety of ecosystems in Canada were examined for their ability to
      mineralize 14C-labelled toluene, naphthalene, dodecane, hexadecane, 2
      chlorobiphenyl, and pentachlorophenol. A number of the psychrotrophic strains
      mineralized toluene, naphthalene, dodecane, and hexadecane. None of the
      psychrotrophs were capable of mineralizing 2-chlorobiphenyl or pentachlorophenol.
      Those strains demonstrating mineralization activity were subsequently screened by
      the polymerase chain reaction (PCR) and Southern hybridization of PCR products
      for the presence of catabolic genes (alkB, ndoB, todCl, and xylE) involved in
      known bacterial biodegradative pathways for these compounds. Some of the
      psychrotrophs able to mineralize toluene and naphthalene possessed catabolic
      genes that hybridized to xylE or todCl, and ndoB, respectively. The alkB PCR
      fragments obtained from the strains that mineralized dodecane and hexadecane did
      not hybridize to an alkB gene probe derived from Pseudomonas oleovorans.
      Psychrotrophic strain Q15, identified as a Rhodococcus sp., also mineralized the
      C28 n-paraffin octacosane. A gene probe constructed from the "alkB" PCR fragment
      from strain Q15 did hybridize with the alkB PCR fragments from most of the
      psychrotrophic alkane biodegraders, indicating that the alkB primers may be
      amplifying another gene(s), perhaps with low homology to P. oleovorans alkB,
      which may be involved in the biodegradation of both short chain (dodecane) and
      longer chain alkanes (hexadecane, octacosane). All of the psychrotrophic
      biodegradative isolates examined were capable of mineralization activity at both
      23 and 5 degrees C, indicating their potential for low temperature bioremediation
      of petroleum hydrocarbon contaminated sites.

PMID- 8742354
TI  - Distribution of diaminopropane and acetylspermidine in Enterobacteriaceae.
AB  - Polyamines of 97 strains (60 species) belonging to 18 genera of the family
      Enterobacteriaceae were determined by high performance liquid chromatographic
      analysis. In addition to putrescine and cadavarine, diaminopropane was widely
      distributed in Enterobacteriaceae and almost ubiquitously within Enterobacter,
      Pantoea, Erwinia, Leminorella, Proteus, Leclercia, Morganella, Klebsiella,
      Hafnia, Rahnella, Serratia, and Tatumella species and sporadically within
      Citrobacter, Escherichia, Moellerella, Providencia, Yokenella, and Yersinia
      species. Histamine was detected in some cultures of Proteus and Morganella.
      Agmatine was sporadically spread. Heterogeneity in the occurrence of spermidine
      was observed within the spermidine-containing cultures. Distribution profiles of
      18 genera. Acetylated spermidine was found concomitantly in the spermidine
      containing cultures. Distribution profiles of diaminopropane, spermidine, and
      acetylspermidine in Enterobacteriaceae can serve as a chemotaxonomic marker to
      distinguish this family from other taxa of the gamma subclass of the class
      Proteobacteria.

PMID- 8742355
TI  - Phenotypic characterization and virulence of a sae- agr- mutant of Staphylococcus
      aureus.
AB  - A sae::Tn551 agr::tetM double mutant was constructed and characterized. The
      production of several exoproteins (e.g., beta-hemolysin, DNase, and proteases) by
      this mutant was determined and found to be lower than the already diminished
      production of either isogenic single mutant sae- or agr-. The double mutant also
      showed, like the agr- mutant, null production of alpha- and delta-hemolysins and
      diminished levels of lipase. The reduced levels of many exoproteins in the double
      mutant as compared with their already diminished levels in either single mutant
      suggest that there is an additive or synergistic interaction between the two
      mutations involved, sae- and agr-. However, inactivation of both loci, sae and
      agr, had a different effect on the two exoproteins that are up regulated in the
      agr- mutant; thus, coagulase dropped to levels close to the null levels of the
      sae- parental strain, while extracellular protein A displayed the high levels
      characteristic of the agr- single mutant. The virulence of the sae- agr- double
      mutant, determined by intraperitoneal injection in mice, was found to be
      significantly diminished as compared with that of the sae+ agr+ parental strain
      or the sae- agr+ single mutant.

PMID- 8742356
TI  - Purification and characterization of urease from schizosaccharomyces pombe.
AB  - The urease from the ascomycetous fission yeast Schizosaccharomyces pombe was
      purified about 4000-fold (34% yield) to homogeneity by acetone precipitation,
      ammonium sulfate precipitation, DEAE-Sepharose ion-exchange column
      chromatography, and if required, Mono-Q ion-exchange fast protein liquid
      chromatography. The enzyme was intracellular and only one species of urease was
      detected by nondenaturing polyacrylamide gel electrophoresis (PAGE). The native
      enzyme had a M(r) of 212 kDa (Sepharose CL6B-200 gel filtration) and a single
      subunit was detected with a M(r) of 102 kDa (PAGE with sodium dodecyl sulfate).
      The subunit stoichiometry was not specifically determined, but the molecular mass
      estimations indicate that the undissociated enzyme may be a dimer of identical
      subunits. The specific activity was 700-800 micromols urea.min-1.mg protein-1,
      the optimum pH for activity was 8.0, and the Km for urea was 1.03 mM. The
      sequence of the amino terminus was Met-Gln-Pro-Arg-Glu-Leu-His-Lys-Leu-Thr-Leu
      His-Gln-Leu-Gly-Ser-Leu-Ala and the sequence of two tryptic peptides of the
      enzyme were Phe-Ile-Glu-Thr-Asn-Glu-Lys and Leu-Tyr-Ala-Pro-Glu-Asn-Ser-Pro-Gly
      Phe-Val-Glu-Val-Leu-Glu-Gly-Glu-Ile- Glu- Leu-Leu-Pro-Asn-Leu-Pro. The N-terminal
      sequence and physical and kinetic properties indicated that S. pombe urease was
      more like the plant enzymes than the bacterial ureases.

PMID- 8742357
TI  - Mycoparasitic species of Trichoderma produce lectins.
AB  - Culture filtrates and mycelial extracts of two mycoparasitic Trichoderma species
      were tested for the presence of lectins, by haemagglutination with human and
      marsupial erythrocytes. In Trichoderma viride, haemagglutinating activity was
      present in both mycelial extracts and culture filtrate. While secreted lectins
      were only detected after 6 days of growth, the presence of mycelium-associated
      lectins was first noted in 3-day-old cultures. Agglutinating activity was also
      demonstrated in the mycelium of 6-, 9- and 13-day-old cultures of Trichoderma
      harzianum. In this species, however, lectins were not secreted. In all instances,
      haemagglutination was inhibited by N-acetylgalactosamine and related sugars. This
      is the first report on the occurrence of lectins in Trichoderma spp.

PMID- 8742358
TI  - The repB gene required for production of extracellular enzymes and fluorescent
      siderophores in Pseudomonas viridiflava is an analog of the gacA gene of
      Pseudomonas syringae.
AB  - Two genes, designated repA and repB, are involved in the regulation of the
      synthesis of extracellular pectate lyase, protease, and alginate in Pseudomonas
      viridiflava. The repA gene has been shown to encode a protein highly homologous
      to several bacterial sensors in the two-component regulator family including the
      LemA of Pseudomonas syringae. In this study, the repB locus, initially identified
      in a 6.3-kb EcoRI genomic fragment of P. viridiflava, was further characterized.
      Results obtained from restriction mapping, deletion subclonings, and mini-Mu-LacZ
      fusions indicated that the repB gene was contained within a 0.8-kb HindIII-PstI
      region. Sequence analysis of this repB region revealed the presence of an open
      reading frame, which was predicted to encode a protein similar or identical to
      the gacA response regulator found in P. syringae and Pseudomonas fluorescens. The
      repB gene of P. viridiflava also regulated the production of fluorescent
      siderophores, in addition to the aforementioned extracellular enzymes and
      alginate. The repB or gacA homologs were detected in the genomes of nine other
      strains of P. viridiflava, P. fluorescens, and P. syringae included in the study.
      The data presented here and earlier indicate that the repA/repB gene regulatory
      system of P. viridiflava is analogous to the lemA/gacA system of P. syringae and
      P. fluorescens.

PMID- 8742359
TI  - Isolation and modulation of growth of a colonization-impaired strain of
      Enterobacter cloacae in cucumber spermosphere.
AB  - Enterobacter cloacae A-46 was isolated for use in an environmental containment
      strategy for genetically modified derivative strains with enhanced biocontrol
      activity. The population of E. cloacae A-46, a transposon mutant of the plant
      beneficial bacterium E. cloacae 501R3, increased 10-fold (significant increase at
      P < or = 0.05) in cucumber spermosphere when applied to cucumber seeds along with
      casamino acids. In contrast, strain A-46 was incapable of proliferation in
      cucumber spermosphere in the absence of casamino acids. Populations of strain A
      46 also failed to increase in corn, cowpea, sunflower, and wheat spermospheres in
      the absence of casamino acids, while populations of strain 501R3 increased 3162-,
      512-, 1698-, and 93-fold, respectively. In addition, the persistence of strain A
      46 in corn, cucumber, and sunflower rhizospheres and in natural soil was greatly
      reduced compared with the parental strain 501R3.

PMID- 8742360
TI  - Restriction analysis of actinomycetes chromosomal DNA.
AB  - Actinomycetes DNAs were digested with restriction enzymes to study the presence
      of methylated bases. Analysis showed that the enterobacterial Dam and Dcm systems
      are absent. Methylation at the internal cytosine in CCGG sequences, typical of
      eukaryotes, was also absent. We also tested 18 restriction endonucleases
      recognizing six base pair sequences (all of which were inhibited by methylation).
      Results showed a higher number of restriction sites for enzymes recognizing CG
      rich sequences (CG endonucleases) than for enzymes recognizing AT-rich sequences
      (AT endonucleases). Restriction patterns with CG endonucleases were quite
      uniform, with the remarkable exception of XhoI, which yielded a small number of
      DNA bands. The study performed with AT endonucleases allowed differentiation of
      three groups of enzymes based on different degrees of chromosomal sensitivity.
      One group (BclI and BglII) produced restriction patterns with more abundant
      restriction sites than expected, a second group (ClaI, EcoRI, and EcoRV) yielded
      the predicted number of DNA fragments, and the third group (HpaI, HindIII, XbaI,
      and DraI) produced an unexpectedly low number of fragments. Some individual cases
      of resistance to particular enzymes could be explained by the presence of
      restriction-modification systems with the same specificity.

PMID- 8742361
TI  - Analysis of human interferon-alpha gene promoters by multiple sequence alignment.
AB  - A map of conserved motifs within 11 human interferon-alpha gene promoters was
      developed using multiple sequence alignment. Multiple sequence alignment revealed
      the highly conserved structure of the virus-response element and a second region
      immediately upstream of the tata box. Homolog analysis indicated six families of
      potential promoter elements: (1) tata boxes, (2) GTATGT motifs, (3) virus
      response elements, (4) distal putative interferon regulatory factor binding
      sites, (5) proximal putative interferon regulatory factor binding sites, and (6)
      TG sequences. On the basis of conserved promoter elements, a theoretical model of
      human interferon-alpha gene promoter organization was advanced. Transcriptional
      regulation of human interferon-alpha gene expression is controlled by a tata box
      and four regulatory domains. Experimental verification is necessary to confirm
      the predicted transcriptional control sequences. Proposed experimentation will
      generate insight into the differential transcriptional regulation of human
      interferon-alpha gene expression.

PMID- 8742362
TI  - Relative transcriptional inducibility of the human interferon-alpha subtypes
      conferred by the virus-responsive enhancer sequence.
AB  - This paper addresses the role of transcriptional regulation in the determination
      of the levels of expression of different interferon-alpha subtypes secreted from
      Namalwa cells following infection with Sendai virus. Using RT-PCR to determine
      the relative abundance of mRNA species coding for the various subtypes, we found
      a general correlation with corresponding protein levels, indicative of a role for
      transcriptional control in the determination of levels of individual subtypes. We
      have used reporter gene constructs to compare the inducibility of the virus
      response elements from the IFNA1, A2, A4, and A14 subtype genes cloned upstream
      of a secreted alkaline phosphatase gene. The inducibility of these reporter gene
      constructs broadly correlated with the relative mRNA abundances in both
      transiently and stably transfected Namalwa cells. During work with stable cell
      lines, we found that G418, the drug used for the selection of transfected cells,
      inhibited the induction of interferon by both Sendai virus and double-stranded
      RNA. This inhibition was reversible when G418 was removed from the medium 24 h
      before the addition of virus.

PMID- 8742364
TI  - High yield expression and secretion of the ovine pregnancy recognition hormone
      interferon-tau by Pichia pastoris.
AB  - The early conceptus (embryo and associated membranes) of domestic ruminats
      signals its presence to the maternal uterus through production of interferon-tau
      (IFN-tau). Production of IFN-tau ensures continued production of progesterone,
      the hormone of pregnancy, by the ovarian corpus luteum. This paper reports the
      high-level expression and efficient secretion of biologically active recombinant
      ovine IFN-tau (rOvIFN-tau) by Pichia pastoris. The developed method produces more
      than 80% pure recombinant ovine IFN-tau, obviating the need for further
      purification for many purposes. Initial fermentation studies produced IFN-tau at
      280 mg/liter and demonstrate the potential of this system for large-scale
      production of IFN-tau.

PMID- 8742363
TI  - Role of tyrosine kinases, protein kinase C, and protein kinase A in the
      regulation of interferon-alpha production induced by herpes simplex virus type 1.
AB  - Herpes simplex virus 1 (HSV-1) is able to induce interferon-alpha production by
      natural IFN-alpha-producing cells. In this study, signal transduction in this
      process was examined. It was found that sequestering of calcium by EGTA abolished
      IFN-alpha induction by HSV-infected cells. Stimulation of human PBMC by HSV-1
      infected fibroblasts resulted in the production of inositol triphosphate (InsP3)
      and tyrosine phosphorylation of cellular proteins. The protein kinase C
      inhibitor, H7, and the tyrosine kinase inhibitor, herbimycin A, were able to
      suppress IFN-alpha gene expression as determined by IFN bioassay and RT-PCR. An
      IFN-alpha-specific ELISpot assay revealed that herbimycin A and H7 remarkably
      decreased the number of IFN-alpha-producing cells. PMA or calcium ionophore
      A23187 alone did not increase IFN-alpha production. However, PMA in conjugation
      with ionophores increased IFN-alpha production as early as 2 h. HA1004 and 2',5'
      dideoxyadenosine, which are potent inhibitors of PKA pathway, had no effect on
      IFN-alpha production. In contrast, BrcAMP, a specific PKA activator, inhibited
      the IFN-alpha secretion and number of IFN-alpha-producing cells and to a lesser
      extent reduced the level of IFN-alpha mRNA. Our results indicate that protein
      kinase C, tyrosine kinases, and protein kinase A are involved in the regulation
      of IFN-alpha production in response to HSV-1.

PMID- 8742365
TI  - Regulation and characterization of the interferon-alpha present in patients with
      advanced human immunodeficiency virus type 1 disease.
AB  - To examine a possible association between plasma viremia and interferon-alpha
      (IFN-alpha) in patients with the acquired immunodeficiency syndrome (AIDS), we
      performed IFN plasma immunoadsorption by apheresis (IFN-alpha apheresis) in four
      volunteers with AIDS who had sustained levels of endogenous plasma IFN-alpha. IFN
      alpha apheresis with two plasma volume exchanges was performed daily for 5 days.
      Clinical signs and symptoms and hematologic, virologic, and immunologic
      parameters were monitored. Two subjects developed anemia from phlebotomy, and one
      had a catheter++-associated bacteremia. The IFN-alpha apheresis was effective
      only in transiently removing IFN-alpha: depletion of IFN-alpha led only to its
      rapid reconstitution. Cell-associated HIV-1 was unchanged, but three of four
      subjects had a modest decrease in culturable plasma virus burden following the
      procedures. The recovery of in vivo HIV-1-related IFN-alpha by apheresis allowed
      its biologic and biochemical characterization. The HIV-1 IFN-alpha showed
      characteristics on ELISA, western blot, and biologic assays similar to two
      subspecies of the natural protein. The natural, recombinant, and HIV-1-induced
      IFN-alpha s demonstrated nearly identical antiviral activities. The HIV-1 IFN
      alpha eluted from the column was not acid labile. The inability of large amounts
      of plasma IFN-alpha found in some patients with AIDS to affect viral burden
      likely reflects properties of the virus or of host factors independent of IFN
      alpha.

PMID- 8742366
TI  - Interferon-alpha enhances the cytotoxic and cytostatic activities of
      chemotherapeutic drugs in human myeloid leukemia cells.
AB  - In comparison with chemotherapeutic drugs, IFN-alpha showed a significantly
      better median survival rate in CML patients; therefore, current studies focus on
      the identification of the proper chemotherapeutic drug, with the most effective
      synergistic interaction with IFN-alpha for the elimination of the human myeloid
      leukemia cell clone. The cytostatic and cytotoxic effects of combining IFN-alpha
      with each of the three chemotherapeutic drugs carboplatin, daunorubicin, and
      cytarabine were evaluated in three human myeloid leukemia cell lines representing
      different stages of differentiation: MHH225 (CD34-positive multilineage), HL-60
      (promyelocytic), and U937 (monoblastic) in both liquid suspension and agar
      clonogenic cultures. The ED90 (the concentrations of chemotherapeutic drugs
      required for 90% inhibition of colony formation or cell death) in human myeloid
      leukemia cells were in the following order: daunorubicin > carboplatin >
      cytarabine, with HL-60 the most sensitive and MHH225 the least sensitive. Whereas
      IFN-alpha failed to decrease significantly the ED90 of cytarabine in the three
      human myeloid leukemia cell lines, it significantly decreased the ED90 of
      carboplatin and to a lesser extent daunorubicin in both liquid suspension and
      agar clonogenic cultures. The present results are in line with the previous
      results of a negative interaction between IFN-alpha and cytarabine both in vitro
      in K562 human leukemia and in vivo in L1210 murine leukemia, and a synergistic
      cytostatic interaction between IFN-alpha and carboplatin in K562 cells. The
      significant synergism between IFN-alpha and carboplatin was observed in all four
      human myeloid leukemia cell lines with various stages of differentiation and
      confirmed in both serum-free and serum-supplemented cultures applying different
      in vitro assays: liquid suspension, agar clonogenic, and capillary agar
      microclonogenic cultures. Thus, given the in vitro profound synergism between IFN
      alpha and carboplatin in all four human myeloid leukemia cells tested, together
      with the in vivo significant antileukemic activity of both IFN-alpha and
      carboplatin in several reported clinical studies for myeloid leukemia patients,
      the clinical use of the combination of IFN-alpha and carboplatin in the treatment
      of CML patients could prolong the complete hematologic and cytogenetic responses
      and consequently improve the survival rate. On the other hand, given the negative
      interaction between IFN-alpha and cytarabine observed in myeloid leukemia cells,
      together with the inferior cytogenetic responses observed in CML patients treated
      with the combination of IFN-alpha and cytarabine, caution should be exercised
      against the continuous clinical use of the combination of IFN-alpha and
      cytarabine in treating CML patients. In conclusion, the present results suggest
      the use of carboplatin and to a lesser extent daunorubicin instead of cytarabine
      in combination with IFN-alpha for the treatment of CML patients.

PMID- 8742367
TI  - Enzyme-linked immunosorbent assay for ovine interferon-tau.
AB  - Ovine interferon-tau (OvIFN-tau) is a trophectoderm secretory protein responsible
      for maintenance of corpus luteum function during early pregnancy. Methods for its
      quantitation include an antiviral assay and radioimmunoassay (RIA), both of which
      have disadvantages. We therefore developed an ELISA for OvIFN-tau that is
      specific, rapid, and 40-fold more sensitive than the current RIA. It uses a
      monoclonal antibody (Ab) HL129, which binds both native and recombinant (r) OvIFN
      tau. The ELISA accurately detected known amounts of rOvIFN-tau added to yeast and
      tissue culture medium and to sheep serum at concentrations between 0.005 and
      50,000 ng/ml. Inter- and intraassay coefficients of variation were 9.3 +/- 0.8
      and 6.1 +/- 1.4%, respectively. Data are given for the reliability and
      reproducibility of the ELISA for measuring native OvIFN-tau and rOvIFN-tau.

PMID- 8742368
TI  - Use of bed rest and head-down tilt to simulate spaceflight-induce immune system
      changes.
AB  - Bed rest, both with and without head-down tilt, has been extensively used as an
      earth-bound analog to study physiologic effects mimicking those occurring in
      weightlessness during spaceflight. We have been able to show in six subjects that
      4 weeks of head-down tilt bed rest induces a significant decrease in interleukin
      2 secretion by PHA-stimulated T lymphocytes. Another study, lasting 113 days,
      with two subjects showed a decreased interleukin-2 receptor expression in PHA
      stimulated peripheral blood mononuclear cells but a decreased interleukin-2
      production in one subject only. Under the same conditions, interleukin-1
      production was largely increased in both subjects. Several other immune
      parameters were also analyzed. Increased interleukin-1 production could
      contribute to bone mineral loss encountered during bed rest and decreased
      interleukin-2 secretion could play a role in the appearance of infectious
      diseases often observed during bed red.

PMID- 8742369
TI  - Kinetics and dose dependence of macrophage colony-stimulating factor-induced
      proliferation and activation of murine mononuclear phagocytes in situ:
      differences between lungs, liver, and spleen.
AB  - Alveolar macrophages (AM) play an important role in antimicrobial defense
      mechanisms of the lung. It therefore seems reasonable to use macrophage colony
      stimulating factor (M-CSF) to enhance local resistance mechanisms. However,
      little is known about the in vivo activity of M-CSF on macrophages in various
      organs. We determined the effect of a single subcutaneous dose of M-CSF (10, 50,
      100, and 500 ng, respectively) on the number and functional status of AM as well
      as of macrophages in liver and spleen of mice. Organs were investigated
      immunohistochemically on days 1 and 3 after injection using monoclonal antibodies
      specific for F4/80, Ia antigen, and MAC-1. We found a significant increase in the
      number of F4/80+ AM, Kupffer cells, and splenic macrophages reaching its maximum
      24 h after injection of low doses (10 and 50 ng per mouse, respectively) of M-CSF
      and decreasing to a level seen in untreated mice at 72 h after M-CSF in liver and
      spleen, whereas at a dose of 50 ng per mouse the number of AM remained high. In
      contrast, the numbers of AM, Kupffer cells, and splenic macrophages did not
      increase significantly when high doses were used (500 ng). The expression of Ia
      antigen and MAC-1 was increased on macrophages in the spleen but not on AM or
      Kupffer cells. TNF-alpha was elevated in bronchoalveolar (BAL) fluid after 3 h
      and IL-6 at 6, 12, and 24 h after M-CSF injection in dose-dependent manner.
      Nitric oxide production was not increased after injection of M-CSF. Our results
      point to regional differences in the response of macrophages to M-CSF. These may
      caused by differences in the M-CSF-induced production of TNF-alpha and IL-6.
      These findings may be important for the therapeutic use of M-CSF in microbial
      infections.

PMID- 8742370
TI  - Synergistic effects between recombinant interleukin-2 and the synthetic
      immunomodulator murabutide: selective enhancement of cytokine release and
      potentiation of antitumor activity.
AB  - The use of interleukin-2 (IL-2) in the treatment of cancer has shown limited
      efficacy and dose-limiting toxicity. Combination therapy with other cytokines
      and/or chemotherapeutic agents has been attempted to enhance the antitumor
      activity and to reduce the effective therapeutic dose of IL-2. We recently
      showed, in vitro and in vivo, a synergistic activity between the synthetic
      immunomodulator murabutide, which is in clinical stage of development, and
      another therapeutic cytokine, interferon-alpha (IFN-alpha). The present study was
      performed to assess a possible potentiation of the biologic activities of IL-2 by
      its association with murabutide. Human PBMC stimulated in vitro with IL-2 and
      murabutide showed synergistic levels of induced mRNA accumulation and protein
      secretion for IFN-gamma, IL-12, and colony-stimulating factors (CSFs). No such
      effects were obtained on the induction of most inflammatory cytokines, including
      IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha). Furthermore, the
      combined administration of murabutide with IL-2 into Meth-A sarcoma-bearing mice
      resulted in a very significant tumor inhibition as well as in complete tumor
      regression in nearly 70% of the treated mice. Under the same conditions,
      treatment with either compound separately had little or no antitumor effect.
      These preclinical findings will be pursued by the evaluation of the clinical
      tolerance and biologic activity of the murabutide/IL-2 combination therapy in
      cancer patients.

PMID- 8742371
TI  - Nomenclature of the human interferon genes.

PMID- 8742372
TI  - Nomenclature of the human interferon proteins.

PMID- 8742374
TI  - Developments in matrix-assisted laser desorption/ionization peptide mass
      spectrometry.
AB  - Most characteristics of matrix-assisted laser desorption/ionization (MALDI) are
      ideal for the analysis of biomolecules. New preparation techniques have
      dramatically increased mass accuracy and resolution, making MALDI a high
      performance mass spectrometric technique for peptide mass analysis. Attempts to
      obtain amino acid sequence information by MALDI have been partially successful.
      The technique has been put to novel uses in protein primary structure
      characterization.

PMID- 8742373
TI  - Characterization of protein glycosylation by mass spectrometry.
AB  - Electrospray ionization, a natural interface with microbore and capillary high
      pressure liquid chromatography, has become the method of choice for the reliable
      structural characterization of protein glycosylation by mass spectrometry at the
      picomole level. Its advantages include inherent sensitivity in the femtomole
      range, compatibility with collisional activation methods that both permit the
      detection and monitoring of structurally specific ions and enable the induction
      of glycopeptide fragmentation that facilitates determination of glycoform
      sequence and branching. Developments in high-performance electrospray mass
      spectrometry include sample introduction at nanoliter flow rates, tandem magnetic
      sector/orthogonal time-of-flight instruments, Fourier transform instruments, and
      new ion optical strategies, including ion traps. Although a sensitive and
      important complementary technique, matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry suffers from matrix-dependent deposition of
      excess internal energies, which produce extensive metastable fragmentation and
      (photo)adduct formation. These metastable fragments may be focused into a mass
      spectrum by employing an ion mirror (reflectron) in time-of-flight
      instrumentation. In favorable cases, structural information may be obtained.

PMID- 8742375
TI  - Non-invasive glucose monitoring.
AB  - Several recent reports claim success in measuring blood glucose non-invasively in
      human subjects with near-infrared spectroscopy. A critical examination of these
      published results suggests more fundamental research is needed to verify the
      validity of these claims. In addition, progress continues in assessing the
      utility of near-infrared spectroscopy as a non-invasive probe for continuous
      bioreactor monitoring during fermentation processes. Recent work demonstrates
      that five critical fermentation components, including glucose, may be measured
      simultaneously.

PMID- 8742376
TI  - Amperometric biosensors.
AB  - Over the past 18 months, our understanding of the chemistry and engineering
      principles of amperometric biosensors, including bioaffinity sensors, has
      deepened. In addition, several novel amperometric biosensors have been
      commercialized and progress has been made in the design of subcutaneous sensors,
      particularly those for glucose.

PMID- 8742377
TI  - Biomagnetic neurosensors.
AB  - Non-invasive measurement of the neuromodulatory activity of certain analytes is
      now possible through the use of biomagnetic stimulation and detection techniques.
      The timely development of room-temperature instrumentation and of more effective
      techniques for coupling neurons to transducers are the critical elements for
      rapid progress in this field.

PMID- 8742378
TI  - Advances in immunoassay technology.
AB  - Major developments continue to be reported in key areas of immunoassay
      technology. Following the development of excellent signal generation methods,
      attention has shifted to the development of immunochemical methods and
      instrumentation to provide convenient systems of high performance. Important
      advances have been made in the design of immunochemical approaches that permit
      the replacement of competitive format assays for small molecules, such as drugs,
      metabolites and pollutants, with non-competitive formats, bringing advantages
      previously seen only with large molecular analytes. Bispecific antibodies and
      recombinant proteins are also beginning to impact immunodiagnostics, with the
      promise of even more highly specified reagents. Improvements in automation have
      brought the facility of homogeneous systems to high-throughput and high
      performance heterogeneous systems. Similarly, 'point of need' testing continues
      to progress. Through all of these advances, systems are evolving according to the
      needs of users in terms of operator convenience, accuracy, specificity, speed,
      robustness, and sensitivity.

PMID- 8742379
TI  - Immunosensors.
AB  - Immunosensors are important analytical tools for monitoring antibody-antigen
      reactions in real time. Recent developments in immunosensors have produced
      systems that allow rapid and continuous analysis of the binding event without the
      requirement for added reagents or separation/washing steps. As a result, great
      interest has focused on commercializing immunosensors for applications in areas
      such as clinical, environmental and food analysis.

PMID- 8742380
TI  - High-density gridding: techniques and applications.
AB  - Much progress has been made in the development of techniques for constructing
      dense grids either of ligands, such as peptides and oligonucleotides, or of
      cloned nucleic acids. Such arrays are finding practical applications in the
      analysis of sequence variation and gene expression. Methods for carrying out
      large numbers of analyses in parallel will be essential for the genetic programme
      that is developing from large-scale sequencing projects.

PMID- 8742381
TI  - The challengers to PCR: a proliferation of chain reactions.

PMID- 8742382
TI  - Analytical biotechnology.

PMID- 8742384
TI  - Alcohol abuse in urban Indian adolescents and women: a longitudinal study for
      assessment and risk evaluation.
AB  - Empirical studies of American Indian health and mental health have focused
      primarily on reservation samples or small cross-sectional school-based or
      treatment samples. Few studies have addressed these issues among urban American
      Indian populations. This paper introduces an ongoing ten-year prospective
      longitudinal study of alcohol abuse, drug abuse, and mental health status in a
      community sample of urban American Indian adolescents and women. The study uses
      structured interviews and diagnostic assessments to identify risk factors for,
      and measure prevalence of, alcohol abuse, drug abuse, and psychopathology in 523
      Indian youth and 276 Indian women. Study aims, rationale, research design,
      methods, sample characteristics, assessment instruments, and substance use
      prevalence are described, and methodological issues related to conducting
      longitudinal research are discussed.

PMID- 8742385
TI  - [Epidemiological study of nosocomial meningitis in neurological patients].
AB  - We realized a retrospective study of all the patients who developed a nosocomial
      meningitis after to admitted to the Intensive Care Unit of our hospital, during
      the last five years. Nosocomial meningitis was found in 3.29% of the neurologic
      patients. The most frequent causes of the meningitis was the external ventricular
      drainage (14.8%), post-neurosurgical (0.8%) and head injury (0.0007%). The
      causative bacterias were stafilococo, S. pneumoniae, K. pneunomiae and P.
      aeruginosa. The mortality was of the 39.06%.

PMID- 8742386
TI  - [The presentation form of headache in children].
AB  - The purpose of the present study was to assess an retrospective analysis on 167
      children with chronic or severe headache, ranged in age from 2 to 14 years (7.19
      +/- 2.36 years old) who were referred to the pediatric neurology service of
      Virgen del Rocio Hospital of Sevilla from december 1992 to december 1994. The
      most common type of headache was migraine which constituted 43.91% of all these
      cases. Tension headache accounted for 27.71%. A family history of headache,
      primarily maternal, was found in 114 patients in whom it could be evaluated.
      Children with migraine had a greater proportion of mothers with a history of
      migraine than those with tension headache. No significant variations were
      observed between chronic evolution and acute. We conclude that headache is not
      uncommon in children and it treatment must be individualized and requires more
      than just the use of pharmacotherapy.

PMID- 8742387
TI  - [A preliminary study of low dosage zuclopenthixol depot in Alzheimer's disease].
AB  - Persistent psychomotor agitation and psychotic ideation in patients with
      Alzheimer's disease are normally treated orally with antipsychotic drugs and are
      occasionally treated with other drugs. Neuroleptics administered intramuscularly
      at very low doses are an alternative, especially when the patient rejects
      medicine as a results of his or her anosognosia or of paranoid manifestations. We
      present the results we obtained after observing the effects of depot
      zuclopenthixol in six patients with probable Alzheimer's disease (based upon
      NINCDS-ADRDA criteria). Psychic abnormalities were assessed as per the Brief
      Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive
      Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS).
      Possible extrapyramidal side effects were evaluated by means of the Abnormal
      Involuntary Movement Scale (AIMS). Initially 60 mg (0.3 ml) were administered
      intramuscularly and successive doses could be modified by +/-20 mg (0.1 ml)
      according to results seen on the various scales. During the first six weeks of
      treatment progressive improvement was noted on all three psychic functions scales
      in all patients. Between the sixth and twelfth weeks improvement continued
      although without significant change. The AIMS did not show significant changes in
      the twelve weeks of follow-up. We consider depot zuclopenthixol at low doses as
      efficacious in treating persistent psychomotor agitation and/or psychotic
      manifestations of Alzheimer's disease. No undesired side effects were observed in
      our group after a twelve week follow-up.

PMID- 8742388
TI  - [Unexpected clinical diagnosis of myotonia].
AB  - We studied all the electromyographic studies carried out in our Service until
      1995, in order to quantify the find of myotonia and to compare it with the
      previous clinical diagnosis that originated the exploration. 30% of the findings
      of myotonia were unexpected. Non-filiated myopathy and weakness on study, were
      the principal clinical correlates in those unexpected findings. It must be noted
      the importance of misdiagnosed myotonia on the epidemiological data of myotonic
      dystrophy.

PMID- 8742389
TI  - [Neurological impairment in children with HIV infection].
AB  - We retrospectively checked 53 paediatric patients suffering from infection with
      human immunodeficiency virus (HIV) registered in our Centre between the years
      1987 and 1993, and evaluated the appearance of HIV encephalopathy. We noted
      important neurological signs in eleven patients (20.7%) ten of whom had HIV
      infection via vertical transmission and one as a result of contamination from
      haemoderivatives. In this review we give a detailed description of neurological
      signs, the moment of onset of these signs and their possible relationship with
      the state of the HIV infection. We also analyzed the resulting neuroradiological
      findings as well as any abnormalities in cerebrospinal fluid. Follow-up period
      ranged from one month to two and a half years from the moment of onset of the
      appearance of encephalopathy. Although most of our patients showed a clear
      improvement after oral or intravenous treatment with zidovudine, this improvement
      generally proved to be short-lived. The mortality rate in our HIV encephalopathy
      series was 81.8%, this figure being reached two and a half years after
      encephalopathy. The appearance of neurological signs in HIV patients therefore
      represents a very gloomy prognostic factor in the evolution of the disease.

PMID- 8742390
TI  - [Voluntary changes of visual evoked potentials in cases with hysteria and/or
      simulation].
AB  - We report a 25-year-old woman with gradual loss of visual acuteness, during
      puerperium and blindness in fifteen days. Two months latter she remain steady.
      Visual evoked potentials using monocular checkerboard pattern-reversal, were
      abnormal. Clinical suspicion of voluntary alteration of VEP was considered. A
      second VEP exploration with binocular stimulation and maneuvers of distraction
      were carried out. Normal VEP were recorded. Deliberate alteration of the visual
      evoked potential should be considered in patients suspicious of hysteria or
      malingering.

PMID- 8742391
TI  - [Frontal dementia-motor neuron disease: a case report and literature review].
AB  - The association between frontal dementia and motor neurone disease has been known
      for years now although its existence as a nosologic entity in its own right is
      still subject to debate. Lack of strict histological criteria and inspecificity
      in complementary tests which might otherwise lend weight to such a diagnosis
      prevent our considering it as much more than a mere clinical syndrome. We present
      here the case of a 56 year old female patient who developed a type of dementia
      with frontal characteristics associated with motor neurone disease. We discuss
      the clinical picture and review the relevant literature.

PMID- 8742392
TI  - [Acute paraparesis associated with dorsal diastematomyelia in an adult].
AB  - Diastematomelia presenting in adult life has long been considered a rare
      occurrence. With the development of modern imagining techniques, cases of adult
      are being discovered with increasing frequency, but their exact number remains
      unclear. It occurs most often in the lumbar region, is rarely located above the
      level of T3 and it present clinical features such as deformity of the food,
      peculiar posture, or gait disturbance. The symptoms and signs of diastematomelia
      usually are recognized in children. We are reporting the case of an adult patient
      who had a forme frustre of Sjogren's syndrome and thoracic diastematomelia
      presenting as a acute myelopathy. Although in most of patients, the pathogenesis
      of the neurological deficits could be attributed to lesions such as spondylosis,
      herniation of a disc, traction injury or the tethering effect derived from an
      osseous septum or a fibrous band, in our patients was absent. We suggested as
      contributory cause to damage of the spinal cord a vascular ischemic mechanism
      during flexion and extension of the spine, and we postulated the role that anti
      Ro (SS-A) antibodies play in the immunopathogenesis (mediating or potentiating)
      vascular injury by altering vascular endothelial function or proliferation.

PMID- 8742393
TI  - [Non-ketotic hyperglycinemia. Transient neonatal form].
AB  - We report a patient with neonatal epilepsy, with no pattern of burst-suppression,
      secondary to the transient form of nonketotic hyperglycinemia. Biochemical
      normalization at two weeks of age was followed by a good clinical evolution and
      neurological normality at one year of age. The patient showed markedly retarded
      myelination and microcysts in the frontal white matter, both transitory and with
      subsequent neuroradiological normalization. Only five patients have been
      previously described with this clinical variant, there being suspicion of a
      glycine cleavage system deficiency due to neonatal enzymatic immaturity.

PMID- 8742394
TI  - [Parainfectious transverse myelitis in an adolescent. Difficulties in the
      etiological diagnosis].
AB  - A diagnostic process in a 13 year-old boy with a parainfectious transverse
      myelitis is described. Its onset was acute, with L1-location level of lesion.
      After a mild improvement, a relapse happened 26 days later, with a D6 level and
      without subsequent recovery. It has not been found criteria for diagnosis of
      multiple sclerosis, nor data suggesting a vascular or ischaemic anomaly.
      Likewise, other causes and specific infections were rejected, being cataloguet as
      parainfectious etiology, due a previous viral infection before its onset.

PMID- 8742395
TI  - [Multiple radicular tumors in von Recklinghausen disease assessed by magnetic
      resonance].
AB  - We present a case of multiple neurofibromata at lumbar nerve root level in a
      patient diagnosed as having Von Reckling-hausen's disease or type 1
      neurofibromatosis (NF 1), studied using magnetic resonance (MR). We also observed
      in the same study the presence of dural ectasis, something likewise related to NF
      1. We assessed MR possibilities in the study of this type of pathology and its
      relative advantages with respect to other types of image-forming techniques. MR
      is nowadays considered as the technique of choice when studying medullar and
      radicular pathology in patients suffering Von Recklinghausen's disease.

PMID- 8742396
TI  - [Symptomatic chronic hemichorea of a vascular lesion in the contralateral
      putamen].
AB  - We present a case of chronic multifocal choreform dyskinesia with evident
      anatomical and temporal relationship with a contralateral putamen lesion of
      ischaemic origin after embolism originating in a partially thrombosed
      intracavernous caratid aneurysm. Isolated putamen lesions are associated with
      abnormal dystonic type involuntary movements, bilateral to Parkinsonisms,
      sometimes associating both these types of movements, and lesions involving the
      cauda giving rise to choreic movements. Given the rarity in the literature of
      this entity, chorea associated with unilateral ischaemic putamen lesion, and the
      absence of pathogenic mechanisms which might satisfactorily explain it, we
      propose a series of possibilities which could underlie this type of chorea. If
      putamen macroscopic lesions are really more associated with dystonic
      manifestations, it is possible that, in some cases they might selectively alter
      base ganglia circuits and bring on chronic choreas rather than dystonia.

PMID- 8742397
TI  - [Untreatable hiccup as un unusual sign in a rostral occlusion syndrome of the
      basilar artery].
AB  - Hiccoughs (singultus) is a habitual physiological phenomenon, the persistence of
      which might indicate neurological and extraneurological multiple lesions. Its
      activation involves starting up numerous central and peripheral mechanisms which
      have yet to be clearly determined. Hiccoughs results from an intermittent
      myoclonus of the diaphragm, reflex in origin, with unknown authentic cause or
      physiological significance. It has been suggested that, more than just an
      abnormal reflex, it could be a type of myoclonus brought on by repeated activity
      of the 'solitary inspiratory nucleus', by releasing control of the inhibiting
      activating upper nervous system activity. We present the case of a patient with
      uncontrollable hiccoughs lasting over six years as a result of paramedial
      bilateral thalamic ischaemia (rostral occlusion syndrome of the basilar artery
      type 1) of cardioembolic origin (auricular fibrillation) secondary to
      hyperthyroidism.

PMID- 8742398
TI  - [Basic concepts. History and evolution of modern neurogenetics].

PMID- 8742399
TI  - [Basic concepts in molecular genetics].

PMID- 8742400
TI  - [Genes, heredity and illness. A critical review of the concepts of genotypes and
      phenotypes].

PMID- 8742401
TI  - [Gene therapy of glioblastomas].

PMID- 8742402
TI  - [Molecular basis of dementias].

PMID- 8742403
TI  - [Miliary metastases to the brain].

PMID- 8742404
TI  - Dissecting human memory with positron emission tomography.

PMID- 8742405
TI  - A matter of life or death: is the Bcl-2 anti-apoptosis gene involved in neural
      plasticity in the olfactory system?

PMID- 8742406
TI  - Contributions of right inferior temporal-occipital cortex to visual word and non
      word priming.
AB  - Little is known about the neural substrates of indirect forms of memory such as
      priming. Electrophysiological (ERP) and behavioral data were recorded from
      controls and three patients with damage in the right parahippocampal and lingual
      gyri, with variable extension into posterior hippocampus and striate/extrastriate
      cortex. Visually presented words and non-words were repeated after one of three
      delays in a lexical decision task. The late positive ERP deflection related to
      stimulus repetition was diminished at all scalp sites, suggesting dysfunction in
      a neural system associated with priming. The patients also failed to show
      significant reaction time priming at intermediate and long delays. These results
      demonstrate the importance of right inferior temporal-occipital cortex for ERP
      and behavioral manifestations of verbal priming.

PMID- 8742407
TI  - MFT in complex partial epilepsy: spatio-temporal estimates of interictal
      activity.
AB  - Magnetic field tomography (MFT) displays three dimensional estimates of the
      distribution of the primary current density vector, Jp, as extracted from non
      invasive, non-contact, magnetoencephalographic (MEG) measurements. MFT was used
      to study the spatiotemporal evolution of the interictal activity during single
      spike events of a patient with complex partial epilepsy. The sequences of events
      of the interictal spikes were analysed in sagittal sections, particularly at the
      depth of the temporal lobe. It appeared that the left-sided interictal spikes
      were usually initiated at the cortical level of the left temporal lobe, the
      activity then propagating to the left amygdaloid and hippocampal formation.
      However, some focal deep activity in this region was obviously initiated in the
      contralateral hemisphere.

PMID- 8742408
TI  - Optical imaging of rat somatosensory cortex reveals representational overlap as
      topographic principle.
AB  - We measured reflectance changes by means of optical imaging of intrinsic signals
      to study the topography of the paw representations in rat somatosensory cortex.
      Following circumscribed tactile stimulation of single digits or pads, we found
      large and partially overlapping areas of reflectance changes (delta R). The
      diameters of their focal zones defined at 75% maximal delta R were in the range
      of 150 microns and preserved all details of the underlying maps. Zones of overlap
      were in the range 15-25% measured at half-maximal delta R. In contrast, we found
      sharp boundaries with no overlap between the fore- and hindpaw representations.
      The data suggest that large and overlapping cortical maps constitute a normal
      type of neural representation supporting the idea of a distributed neural
      processing scheme.

PMID- 8742409
TI  - Sound induced expression of c-Fos in GABA positive neurones of the gerbil
      cochlear nucleus.
AB  - To characterize c-Fos-expressing neurones in more detail, a double labelling
      technique was developed to simultaneously demonstrate the presence of GABA-like
      and c-Fos-like immunoreactivity in cryostat sections of the gerbil cochlear
      nucleus. The animals were exposed to a wide-band noise stimulus for the induction
      of c-Fos expression. The distribution of c-Fos-positive cells and GABA-positive
      somata was consistent with previous reports. Our double labelling approach
      revealed the presence of GABA-positive cells that showed c-Fos expression after
      noise stimulation. One interpretation of this finding is that a prolonged
      acoustic exposure induces long term changes in inhibitory interneurones to adjust
      the output of the cochlear nucleus.

PMID- 8742410
TI  - Responses from new receptive fields of VPL neurones following deafferentation.
AB  - Single unit recordings were made from the ventral posterior lateral thalamus of
      anaesthetized rats to characterize responses to the activation of new receptive
      fields induced by either local anaesthesia or amputation. Receptive fields
      confined to single digits were identified and evoked unit responses to the
      stimulation of single digits were quantitated before and after deafferentation.
      Although both methods of denervation rapidly induced similar new receptive fields
      from the adjacent single digit, they exhibited quite different temporal changes
      of the evoked unit responses from new receptive fields. This difference in the
      evoked unit responses from the new receptive fields may be related to either the
      different nature or the outcome of the two types of deafferentation.

PMID- 8742411
TI  - Kinetics of A-currents in sympathetic preganglionic neurones and glial cells.
AB  - Transient outward currents (A-currents; IA) were recorded in sympathetic
      preganglionic neurones (SPNs) and glial cells of the intermediolateral cell
      column (IML) by whole-cell recordings in rat spinal cord slices. In both cell
      types IA activated at around -45 mV and the time-course of decay was
      monoexponential, but faster in glial cells than in neurones. In both cases decay
      time constants displayed the same increase with depolarization above -30 mV. In
      neurones, the activation curve was shifted to more negative value along the
      voltage axis and was steeper than the activation curve for glial cells whereas
      inactivation curves were similar. Recovery from inactivation followed a double
      and monoexponential decay in neurones and glial cells, respectively.

PMID- 8742412
TI  - Cardiotrophin-1 is not the sweat gland-derived differentiation factor.
AB  - Sympathetic neurons innervating sweat glands undergo a target-directed switch in
      neurotransmitter properties. Although the factor responsible for inducing this
      switch has not been identified, it appears to be a member of the neuropoietic
      cytokine family. Cardiotrophin-1 (CT-1), a new family member, was analyzed to
      determine whether it was a relevant factor. CT-1 induced choline acetyl
      transferase and vasoactive intestinal peptide in cultured sympathetic neurons,
      and RT/PCR amplified CT-1 mRNA from footpad total RNA. The differentiation
      activity of CT-1 was blocked by CT-1 antiserum. The activity in sweat gland
      extracts and cultures was not, however, suggesting that CT-1 is not the sweat
      gland-derived factor.

PMID- 8742414
TI  - Sulphated compounds attenuate beta-amyloid toxicity by inhibiting its association
      with cells.
AB  - Agents that interfere with the toxic effects of beta-amyloid protein may be
      therapeutically useful against Alzheimer's disease. We reported recently that
      several sulphated glycosaminoglycans and sulphonated dyes attenuate the toxic
      effects of beta-amyloid fragments beta 25-35 and beta 1-40 in two clonal cell
      lines. We now demonstrate that this protective effect is due to interference with
      beta-amyloid cell association rather than effects on beta-amyloid structure.
      Using an enzyme-linked immunoabsorbance assay to detect cell-associated beta 1
      40, we found in a range of compounds a strong correlation between inhibition of
      HeLa cell association of beta 1-40 and attenuation of cellular toxicity as
      measured by inhibition of 3-[4,5-dimethylthia-zol-2-yl]-2,5-diphenyltetrazolium
      bromide (MTT) reduction. In contrast, effects on peptide structure, as measured
      by Congo red binding, were generally inconsistent with the attenuating effects of
      the compounds on cellular toxicity. These results suggest that by binding beta
      amyloid these agents prevent its interaction with cells.

PMID- 8742413
TI  - Distribution of NMDA receptor subunit proteins NR2A, 2B, 2C and 2D in rat brain.
AB  - The regional distribution of the NMDA receptor subunits NR2A, 2B, 2C and 2D was
      visualized in adult rat brain using the histo-blot technique with newly developed
      subunit-specific antisera. NR2A immunoreactivity was found in almost all regions
      of the brain, whereas NR2B staining was restricted to forebrain, and NR2D
      immunoreactivity to diencephalic, mesencephalic and brain stem structures. NR2C
      staining was confined to cerebellum, thalamus and olfactory bulb. Thus, NMDA
      receptors containing the NR2A subunit are likely to represent a receptor subtype
      predominant throughout the brain, while those containing the NR2B, NR2C or NR2D
      subunit represent more region-specific receptor subtypes. The regionally
      overlapping distribution of certain NR2 subunits points to the existence of NMDA
      receptors containing more than one NR2 subunit variant.

PMID- 8742415
TI  - Transfected rat mu opioid receptors (rMOR1 and rMOR1B) stimulate phospholipase C
      and Ca2+ mobilization.
AB  - The mu opioid agonist DAMGO increases intracellular Ca2+ concentration and
      inositol triphosphate formation in Chinese hamster ovary cells stably expressing
      the mu opioid receptors rMOR1 and rMOR1B, a recently isolated isoform of rMOR1.
      The increase in intracellular Ca2+ concentration is due solely to mobilization
      from internal stores. Both the DAMGO-induced stimulation of inositol triphosphate
      and increase in intracellular Ca2+ concentration is similar for both variants
      with an EC50 of about 1 microM, which is about an order of magnitude less
      efficient than the inhibition of adenylyl cyclase (EC50 = 150 microM).

PMID- 8742416
TI  - Analysis of regulatory regions of the ciliary neutrophic factor gene in
      transgenic mice.
AB  - In order to study the regulatory regions of the human ciliary neurotrophic factor
      (CNTF) gene we made constructs containing sequences upstream and downstream of
      CNTF coding regions and the lacZ gene and analysed their expression in transgenic
      mice. We show that 240 bp upstream of the translation start codon are sufficient
      for the transcription of the lacZ gene. A further 4 kb upstream sequence is
      required for the expression of the transgene in Schwann cells. These two upstream
      regions together with a 2 kb downstream fragment drive high level of expression
      of the lacZ gene in the sciatic nerve. Our results indicate that these three
      fragments contain regulatory regions able to mimic the CNTF expression pattern in
      the mouse peripheral nervous system.

PMID- 8742417
TI  - A cautionary note on the use of the TUNEL stain to determine apoptosis.
AB  - Detection of DNA fragments in situ using the terminal deoxyribonucleotidyl
      transferse (TdT)-mediated biotin-16-dUTP nick-end labelling (TUNEL assay) is now
      commonly used to investigate apoptosis. Previous reports suggested that
      physiologically appropriate death is due to apoptosis and that pathological
      mechanisms involve necrosis. Strong evidence of apoptosis, following ischaemia
      and epilepsy, has been recently provided by combining genomic DNA gel
      electrophoresis, light and electron microscopy and in situ, DNA-break labelling.
      However, only an observation in light microscopy with high magnification permits
      the detection of chromatin condensation and apoptotic bodies. We report that a
      positive TUNEL assay reaction should not be considered as a specific marker of
      apoptosis but can also indicate necrotic cell death.

PMID- 8742418
TI  - Neurone decapping characterization by atomic force microscopy: a topological
      systematic analysis.
AB  - We tested a new approach to cell decapping on rat cerebellar neurones, and
      observed its effects on cell topography by atomic force microscopy (AFM). The
      results clearly demonstrate the effectiveness of our decapping approach, and also
      the ability of AFM to reveal fine details of the decapped cells. Specifically,
      varying the conditions and duration of the decapping process modifies the extent
      of the decapping. Such a method can be used to investigate the cytoplasm with
      surface sensitive techniques.

PMID- 8742419
TI  - Inhibition of [3H]CGP 39653 binding to NMDA receptors by a P2 antagonist,
      suramin.
AB  - Suramin, which has been used for more than 50 years as an anthelmintic in humans,
      has recently been shown to inhibit P2 purinoceptors in the CNS and to block
      glutamate-evoked excitatory potentials in hippocampus. We now report that suramin
      inhibits (IC50 approximately 100 microM) the binding of [3H]CGP 39653, a ligand
      specific for NMDA-type glutamate receptors in brain. Consequently, suramin at
      concentrations used sometimes in physiological experiments may act as both P2x
      and NMDA antagonist. Since both NMDA receptors and P2x-subtype of purinoceptors
      form Ca(2+)-selective channels, suramin may block Ca2+ entry into neurones
      depolarized by either ATP, L-glutamate or any other neurotransmitter or drug
      acting via P2x or NMDA receptors.

PMID- 8742420
TI  - SNAP-25 is the major immunoreactive component of the brain-specific D3 protein.
AB  - The rat synaptosomal membrane antigen D3, which has been studied for more than 20
      years since its first demonstration as a brain-specific protein, was shown to
      bind monoclonal antibodies to SNAP-25, a presynaptic plasma membrane-associated
      protein. In addition to SNAP-25, anti-D3 antiserum also precipitated two
      polypeptides of 34-36 kDa and 14-16 kDa. This suggests that anti-D3 binds all
      three of the 20S synaptic vesicle fusion particle components, i.e. SNAP-25,
      syntaxin, and vesicle-associated membrane protein (VAMP)/synaptobrevin. However,
      the botulinum toxins C and D, which are endoproteases selective for syntaxin and
      VAMP/synptobrevin, respectively, were unable to remove the D3 immunoreactivity
      from synaptosomal membranes. Therefore, it is concluded that D3 immunoreactivity
      is directed only against SNAP-25.

PMID- 8742421
TI  - Cellular prion protein and GABAA receptors: no physical association?
AB  - The so-called prion diseases are probably caused by the conformational conversion
      of the cellular prion protein (PrPc) into an abnormal, pathological form (PrPsc).
      PrPc is widely expressed in neuronal tissues, but its function is not known. From
      electrophysiological measurements in prion-less mice it was proposed that PrPc
      may contribute to the structural integrity of central synapses containing gamma
      aminobutyric acid type A (GABAA) receptors. We tried to substantiate this
      hypothesis by obtaining evidence for a structural link between the GABAA receptor
      and PrPc. Preparations of PrPc and GABAA receptors, respectively, from cow brain
      were analysed for PrPc-GABAA receptor complexes. No evidence for such complexes
      could be obtained in our experiments, although the protein purification schemes
      used should favour the preservation of intermolecular linkages. We conclude that
      further data concerning interactions of PrPc with other proteins are needed to
      obtain insight into its normal functional role.

PMID- 8742422
TI  - Effect of chronic toluene exposure on tyrosine hydroxylase-positive nerve
      elements in the rat forebrain: an immunohistochemical study combined with
      semiquantitative morphometric analysis.
AB  - The effects of chronic toluene exposure [3000 p.p.m. for 4 h (09:00-11:00, 13:00
      15:00)] every day for 3 weeks on immunoreactivity for tyrosine hydroxylase (TH),
      the rate limiting enzyme of catecholamine synthesis, in the rat forebrain were
      studied. In toluene-exposed rats, increases in both number and intensity of TH
      immunoreactive fibres and terminals were observed in most parts of the forebrain
      including the cerebral cortex, hippocampus, lateral septal nucleus and
      hypothalamus, compared with control rats. These findings suggest that chronic
      toluene exposure might influence catecholaminergic neural systems.

PMID- 8742423
TI  - The influence of prolonged antidepressant treatment on the changes in cyclic AMP
      accumulation induced by excitatory amino acids in rat cerebral cortical slices.
AB  - We investigated the effect of prolonged electroconvulsive shock (ECS) or
      imipramine treatment on cyclic AMP accumulation induced by ibotenate and
      glutamate in rat cerebral cortical slices. Prolonged imipramine or
      electroconvulsive shock treatment attenuated the ibotenate-induced increase in
      cyclic AMP accumulation and inhibited the synergistic interaction between
      ibotenate and noradrenaline; the glutamate-mediated inhibition of forskolin
      stimulated cyclic AMP accumulation was not modified. Our results indicate that
      multiple effects of excitatory amino acids on cyclic AMP accumulation are
      modified differently by antidepressant treatment.

PMID- 8742424
TI  - Protection against veratridine toxicity in rat cortical cultures: relationship to
      sodium channel blockade.
AB  - Neuroprotection against 100 microM veratridine-induced cell death and inhibition
      of voltage-dependent sodium currents by phenytoin, carbamazepine, lidocaine and
      vinpocetine were studied in rat primary cerebrocortical cultures. Neuroprotective
      efficacies and sodium channel blocking potencies of these drugs failed to show a
      correlation, suggesting that (i) mechanisms other than sodium channel blockade
      may be involved in the neuroprotection, and/or (ii) inhibitory efficacy against
      veratridine- and voltage-activated channels may differ remarkably.

PMID- 8742425
TI  - BDNF or IGF-I potentiates free radical-mediated injury in cortical cell cultures.
AB  - Free radical-mediated damage to cultured cortical neurons was induced by a 24 h
      exposure to Fe2+ (30 microM) or an inhibitor of gamma-glutamylcysteine
      synthetase, L-buthionine-[S,R]-sulfoximine (BSO, 1 mM). As expected, neuronal
      death was blocked by inclusion of the free radical scavenger trolox during the
      Fe2+ or BSO exposure. However, unexpectedly, pretreatment of the cultures with
      BDNF or IGF-I markedly potentiated neuronal death. This growth factor-potentiated
      death was still blocked by trolox, but was insensitive to glutamate antagonists.
      Concurrent addition of cycloheximide with the growth factors prevented injury
      potentiation. Present findings suggest that growth factors may increase free
      radical-induced neuronal death by mechanisms dependent upon protein synthesis.

PMID- 8742426
TI  - Affective and attentive neural networks in humans: a PET study of Pavlovian
      conditioning.
AB  - Using positron emission tomography (PET) and [15O]butanol we studied regional
      cerebral blood flow (rCBF) to a visual snake stimulus before and after classical
      conditioning with an unconditioned electric shock delivered to the right hand.
      Measures of heart rate, electrodermal activity, state anxiety and subjective
      distress confirmed classical conditioning of physiological and subjective
      responses. Subcortically, conditioning increased rCBF bilaterally in the
      ventromedial thalamus, the posterior hypothalamus and the central grey of the
      midbrain. Cortically, rCBF increased in the left anterior and posterior cingulate
      gyrus, the left primary somatosensory cortex, the left premotor cortex and
      bilaterally in parietal areas. Thus, the functional organization of classical
      conditioning in humans involves autonomic, affective and attentive brain
      mechanisms.

PMID- 8742427
TI  - Long-term cognitive impairment in MPTP-treated rhesus monkeys.
AB  - Following MPTP administration, monkeys manifest cognitive deficits on tasks known
      to assess the fronto-striatal system; there are, however, no data regarding long
      term cognitive effects. In this study, we examined the cognitive abilities of
      monkeys 10 years after MPTP administration. MPTP-treated monkeys and age-matched
      controls performed a spatial delayed response task with fixed and random delays.
      The MPTP-treated monkeys were impaired in both versions of the task. Both groups
      performed at the same level at very short delays suggesting that the nature of
      the impairment is related to a spatial memory deficit that is still apparent 10
      years after treatment. These results suggest that, like Parkinson's patients, the
      MPTP-treated primates display spatial deficits.

PMID- 8742428
TI  - Presurgical integrated MRI/SPECT localization of the sensorimotor cortex in a
      patient with a low-grade astrocytoma in the rolandic area.
AB  - We describe the case of a young man who, despite the presence of a tumour in the
      left sensorimotor cortex, exhibited no motor deficit. Integrated MRI/SPECT-CBF
      study during motor activation was aimed at determining which cerebral areas were
      involved in movement execution in this patient and their relationship with the
      tumour. CBF changes during motor activation were located in two motor areas:
      anteriorly and medially to the tumour in the left frontal lobe (+29%) and in the
      right medial frontal cortex (+43%). Integrated MRI/SPECT images provided both an
      anatomical and functional definition of the motor areas in a patient with a
      rolandic tumour and could prove useful in determining preoperatively an
      appropriate surgical strategy.

PMID- 8742429
TI  - Neural correlates of working memory in a visual letter monitoring task: an fMRI
      study.
AB  - Complex mental operations rely on the coordinated activity of widely distributed
      brain regions constituting neurocognitive networks. Using multislice echoplanar
      functional magnetic resonance imaging (fMRI) we have contrasted regional brain
      activity during a control and an experimental condition which differed with
      respect to the demands placed on verbal working memory. Subjects were seven right
      handed healthy male volunteers. Analysis of group and individual data revealed
      activation in the anterior and posterior parasagittal cortex in all subjects,
      left parietal cortex (six subjects) and left dorsolateral prefontal cortex (five
      subjects). These results suggest that verbal working memory is subserved by a
      neurocognitive network comprising cortical regions involved in attention,
      executive function and short term mnemonic processes.

PMID- 8742430
TI  - Expression of activin receptors type I and II only partially overlaps in the
      nervous system.
AB  - In situ hybridization was used to localize mRNA encoding two cooperative
      serine/threonine kinase receptors. Activin receptor IIA mRNA in the adult rat
      brain is highly expressed in the dentate gyrus, in the pyramidal neurones of CA3
      and CA1, in the entorhinal cortex, in the cortical amygdaloid nucleus and in the
      amygdalohippocampal area. In the E16 rat embryo, labelling was found in the
      dorsal root ganglion neurones and in the spinal cord. Activin type I receptor
      (ALK-2/R-1) labelling was also localized to the hippocampal formation but with an
      even distribution over the granular cells of the dentate gyrus, the CA3 and CA1
      pyramidal neurones, while no labelling was found in the entorhinal or amygdaloid
      areas. In the E16 rat no neuronal labelling was found. The incomplete overlap of
      these two expression patterns suggests that these receptors may locally have
      other partners for forming signalling receptor complexes.

PMID- 8742431
TI  - The agonist selectivity of a class III metabotropic glutamate receptor, human
      mGluR4a, is determined by the N-terminal extracellular domain.
AB  - To test the hypothesis that the determinants for agonist selectivity of class III
      metabotropic glutamate receptors (mGluRs) are localized in the N-terminal
      extracellular domain, a chimaeric cDNA was constructed where 519 amino acids of
      the N-terminal extracellular domain of human mGluR1b were exchanged with the
      corresponding region of human mGluR4. The pharmacological profile of the
      chimaera, designated hmGlu(R4)1-519/1b, was analysed by recordings of
      intracellular calcium concentration ([Ca2+]i) in transiently transfected HEK 293
      cells and compared with that of human mGluR1b and human mGluR4a stably expressed
      in Chinese hamster ovary cells. Application of 100 microM L-2-amino-4
      phosphonobutyrate (L-AP4), a class III mGluR-specific agonist, induced a rise in
      [Ca2+]i in hmGlu(R4)1-519/1b but not in hmGluR1b expressing cells. In contrast,
      application of quisqualate (100 microM) induced a rise in [Ca2+]i at hmGluR1b but
      not at hmGlu(R4)1-519/1b. Dose-response analysis with L-AP4 and L-glutamate at
      hmGlu(R4)1-519/1b revealed a half-maximal effect (EC50) of 16.0 microM and 196
      microM, respectively. The EC50 values for quisqualate, glutamate and (1S,3R)-ACPD
      at hmGluR1b were 10.25 microM, 225 microM and 3060 microM, respectively. The rank
      order of agonist potency of hmGlu(R4)1-519/1b corresponds to that of hmGluR4 (L
      AP4 > L-glutamate > (1S,3R)-ACPD > quisqualate) but is different from that of
      hmGluR1b (quisqualate > glutamate >> (1S,3R)-ACPD).

PMID- 8742432
TI  - Molecular single-cell analysis identifies somatostatin type 1 (sst1) receptors to
      block inwardly rectifying K+ channels in rat brain oligodendrocytes.
AB  - For the first time whole-cell patch-clamp recordings were performed together with
      a molecular analysis of mRNA expression on single rat cortical oligodendrocytes.
      The neuropeptide somatostatin (3 microM) was found to rapidly (< 1s) induce a 58
      +/- 33% block of the inwardly rectifying K+ current (IKIR). Following recording,
      the cells' cytoplasm was harvested through the patch pipette and processed for
      RNA amplification. Polymerase chain reactions on the amplified products showed
      that of the primers specific for all five somatostatin receptor subtypes (sst1
      sst5), only those derived from sst1 amplified cDNA fragments. Sequence analysis
      of these fragments revealed complete identity to rat sst1 receptors; thus they
      are probably the major subtype of somatostatin receptors that control IKIR in rat
      brain oligodendrocytes.

PMID- 8742433
TI  - Tyrosine phosphorylation of NMDA receptor in rat striatum: effects of 6-OH
      dopamine lesions.
AB  - N-Methyl-D-aspartate (NMDA) glutamate receptor properties are subject to a fine
      tuning by several regulatory mechanisms including phosphorylation of the receptor
      subunits. Here we show that two of these subunits, NR2B and NR2A, are
      phosphorylated on tyrosine residues in vivo, in rat striatum, where NR2B is by
      far the most prominent tyrosine phosphorylated protein. Two weeks after
      unilateral lesioning of nigrostriatal dopaminergic neurones with 6
      hydroxydopamine, tyrosine phosphorylation of NR2B was increased by approximately
      20% in the ipsilateral striatum. The total amount of NR2B protein was unaltered.
      Thus, increased tyrosine phosphorylation of NR2B may account for some of the
      consequences of dopamine deprivation on corticostriatal transmission and may play
      a role in some forms of synaptic plasticity.

PMID- 8742434
TI  - Transport of hydrophobized fragments of antibodies through the blood-brain
      barrier.
AB  - Hydrophobized and non-hydrophobized Fab fragments of human antibodies against
      gliofibrillar acid protein (GFAP) and brain specific alpha 2-glycoprotein (alpha
      2GP) were used to study their penetration through the blood-brain barrier (BBB).
      These Fab fragments were modified by stearoyl chloride in reversed micelles of
      aerosol OT in octane (one or two fatty acid residues attached to protein
      molecule). Modified and non-modified 125I-labelled Fab fragments were
      intracardially administered to rats. The amount of label accumulated in brain was
      55% higher than the total amount in all other organs. In contrast, non
      hydrophobized Fab fragments did not penetrate through the BBB. We assume that the
      artificial hydrophobization of Fab fragments can increase their capability to
      penetrate through the cell membranes and, in particular, the BBB.

PMID- 8742435
TI  - Biphasic transforming growth factor-beta production flanking the pro-inflammatory
      cytokine response in cerebral trauma.
AB  - We determined the time-course of the production of transforming growth factor
      beta (TGF-beta) after fluid-percussion injury using a bioassay. Biophasic
      production of TGF-beta composed mainly of TGF-beta 2 was detected in the
      ipsilateral cortex, with a first peak 30 min and a second peak 48 h after the
      lesion, flanking the transient production of tumor necrosis factor-alpha and
      interleukin-6 occurring between 5 and 18 h after trauma. This temporal pattern
      suggested that TGF-beta plays alternatively a pro- and anti-inflammatory role in
      the regulation of the brain cytokine network in response to injury, providing an
      endogenous mechanism for the control of the inflammatory reaction in traumatic
      brain injury.

PMID- 8742436
TI  - The influence of head rotation on human upright posture during balanced bilateral
      vibration.
AB  - During a balanced bilateral vibration of tensor fasciae latae muscles evoking no
      evident postural changes in a standing human the slow head turns resulted in a
      pronounced lateral common gravity centre displacements to the 'occipital' side.
      Neck influences were most prominent at intermediate tonic background and were
      lacking both during very weak and strong vibratory stimulation in contrast to
      usual tonic vibratory reflex which becomes stronger with the increase of
      frequency. Body sway was induced not only by actual head turns but also by
      illusory ones evoked by neck muscle vibration. The neck influences on standing
      posture are therefore present in healthy adults, but they require a definite
      level of tonic readiness for their manifestation and are incorporated in the
      whole system of body scheme mechanisms.

PMID- 8742437
TI  - Daily variations in 2-[125I]melatonin specific binding in the golden hamster
      retina.
AB  - Daily variations in melatonin content and 2-[125I]melatonin specific binding in
      retinas of golden hamsters were studied. Both parameters showed significant
      variations throughout the 24 h period. Maximal specific binding was observed at
      24.00 h, while melatonin content peaked at 04.00 h. Saturation studies performed
      at 12.00 and 24.00 h indicated that the maximal concentration of 2
      [125I]melatonin binding sites (Bmax) was significantly higher at 24.00 h than at
      12.00 h, whereas the dissociation constant (Kd) remained unchanged. As 2
      [125I]melatonin specific binding decreased at times when retinal melatonin
      content was high, these findings suggest that daily variations in retinal
      melatonin levels may be implicated in the regulation of the density of melatonin
      binding sites, probably through mechanisms of up- and down-regulation induced by
      melatonin on its own binding sites.

PMID- 8742438
TI  - GDNF reduces apoptosis in dopaminergic neurons in vitro.
AB  - To explore the mechanism by which glial cell line-derived neurotrophic factor
      (GDNF) improves cell survival, we measured the apoptotic rate of dopamine neurons
      incubated with GDNF. Cultures were prepared from embryonic day 15 rat
      mesencephalon in medium with 5% human placental serum. GDNF reduced the rate of
      apoptosis in dopamine neurons from 5% to 2%. By contrast, GDNF had no effect on
      apoptoisis in astrocytes from embryonic mesencephalon or from neonatal cortex. Co
      cultures with embryonic striatum as well as with combinations of growth factors
      were also tested for effects on dopamine neuron survival. Neuronal survival was
      maximal during co-culture with striatal cells with or without added growth
      factors. We conclude that GDNF inhibits apoptotic cell death in dopamine neurons.

PMID- 8742439
TI  - Local anaesthesia induces immediate receptive field changes in nucleus gracilis
      and cortex.
AB  - The reorganization of receptive fields of nucleus gracilis neurones after local
      anaesthesia, and its relationship to the reorganization of cortical maps were
      studied in the rat. Cutaneous stimulation was performed using electronically
      gated air jets. Single unit recordings were obtained in gracilis nucleus and
      somatosensory cortex. Temporary anaesthesia was induced with lidocaine (2%, 5-15
      microliters s.c.), which blocked the responses in < 2 min and provoked the
      simultaneous appearance of new overlapping receptive fields in gracilis and
      cortical neurones in 2-30 min. The present results suggest that the early
      reorganization of somatosensory cortical maps after temporary anaesthesia may be
      partly due to the emergence of new receptive fields in nucleus gracilis neurones.

PMID- 8742440
TI  - Human CNTF and related cytokines: effects on DRG neurone survival.
AB  - Ciliary neurotrophic factor (CNTF), leukaemia inhibitory factor (LIF), oncostatin
      M (OSM), interleukin-6 (IL-6), and interleukin-11 (IL-11) are structurally and
      functionally related cytokines. We compared their survival-promoting activities
      on embryonic chick and newborn rat dorsal root ganglion (DRG) neurones. Human
      CNTF showed the well known trophic effect on both chick and rat DRG neurones.
      Human and murine LIF and, at unphysiologically high doses, human OSM were trophic
      for rat neurones, but failed to promote chick DRG cell survival. Human IL-11,
      murine IL-6 and human IL-6 did not improve chick or rat DRG neurone survival;
      soluble human IL-6 receptor alpha did not increase sensitivity to human IL-6.
      Thus, human CNTF as well as murine and human LIF had special neurotrophic
      properties compared with other related cytokines.

PMID- 8742441
TI  - L-NOARG, an inhibitor of nitric oxide synthase, induces catalepsy in mice.
AB  - The objective of this study was to investigate possible motor effects of NG-nitro
      L-arginine (L-NOARG), an inhibitor of nitric oxide synthase. Acute administration
      of L-NOARG (5-80 mg kg-1, i.p.) induced catalepsy in a dose-dependent manner in
      male albino-Swiss mice. The drug had an additive effect with haloperidol (0.125
      0.5 mg kg-1, i.p.). The acute effect of L-NOARG (40 mg kg-1, i.p.) was attenuated
      by previous treatment with L-arginine (300 mg kg-1, i.p.). Sub-chronic treatment
      with L-NOARG (40 mg kg-1, i.p., twice a day for 4 days) was also able to
      attenuate the cataleptic effect of acute drug administration (40 mg kg-1, i.p.).
      These results show that acute systemic injections of L-NOARG induce significant
      motor effects.

PMID- 8742442
TI  - Alterations in MAP2 immunostainability after prolonged complete brain ischaemia
      in the rat.
AB  - Immediate loss of MAP2 immunostainability after very short ischaemic periods (3-5
      min) has been reported in the gerbil. With longer periods of ishaemia this loss
      of immunoreactivity becomes identical with the pattern of ischaemia-induced
      selective neuronal injury. In contrast, in the four-vessel occlusion rat model,
      no such changes were observed during the early recirculation period. As no
      studies have focused on immediate changes due to complete brain ischaemia, we
      studied MAP2 immunoreactivity in the rat after cardiac arrest for up to 30 min.
      We observed a moderate decrease in stainability but the changes did not resemble
      those of selective vulnerability. We conclude that prolonged complete brain
      ischaemia without recirculation in the rat does not cause selective loss of MAP2
      immunostainability in the vulnerable regions.

PMID- 8742443
TI  - Electrophysiological changes in substantia nigra after striatal infarction.
AB  - The GABAergic efferent pathway from the striatum exerts inhibitory control on the
      substantia nigra pars reticulata (SNR) neurones. We studied sequential changes in
      spontaneous single-unit activities in the ipsilateral SNR 1 h, 1 day, 7 days and
      14 days after striatal infarction induced by middle cerebral artery occlusion
      (MCAO) in rats. Compared with a sham-operated group, there was no change in the
      firing rate 1 h after MCAO, and one day after MCAO the mean firing rate
      decreased. The firing rate of SNR neurones at 7 and 14 days after MCAO was
      significantly reduced compared with the sham-operated group. Only two neurones
      (sham-operated group and 1 h after MCAO group) fired with high frequency.
      Histological examination revealed degeneration of the ipsilateral SNR 7 and 14
      days after MCAO. Our results indicated that SNR neuronal degeneration accompanied
      by striatal ischaemia does not simply depend on hyperexcitation due to the
      activation of a disinhibition mechanism.

PMID- 8742444
TI  - Association between clozapine response and allelic variation in the 5-HT2C
      receptor gene.
AB  - A cysteine to serine substitution at amino acid 23 in the 5-HT2C receptor gene
      alters the pharmacological properties of the protein. We investigated this
      polymorphism in subjects with schizophrenia resistant to conventional neuroleptic
      drugs, and analysed our data for allelic association between the disease state or
      clinical response to the atypical antipsychotic drug, clozapine. Ninety percent
      of subjects who had one or more 5-HT2Cser alleles (19/21) were classified as
      clozapine responders compared with 59% (84/141) without this allele (chi 2 = 7.7,
      p = 0.005), suggesting that this mutation is a predictor of good response to
      clozapine. There was no association between schizophrenia and the 5-HT2Cser
      allele, but our results indicate that the 5-HT2C receptor may contain the major
      site of action through which clozapine mediates its antipsychotic effects.

PMID- 8742445
TI  - Guinea-pig sympathetic postganglionic neurones contain haem oxygenase-2.
AB  - HAEM oxygenase-2 (HO-2) is the neuronal isoform of the only known mammalian
      enzyme generating the new transmitter candidate, carbon monoxide. Its
      distribution was investigated in the sympathetic nervous system. A 36 kDa HO-2
      immunoreactive protein was identified in the particulate fraction of stellate
      ganglion and cerebellum in Western blots. Immunohistochemically, all
      noradrenergic and non-noradrenergic postganglionic neurones were HO-2
      immunoreactive in prevertebral ganglia and cervical, thoracic, and lumbar
      sympathetic chain ganglia. Neither postganglionic nerve branches nor
      noradrenergic perivascular terminals were HO-2 immunoreactive under control
      conditions. However, accumulation of HO-2 immunoreactivity was found in
      noradrenergic axons in explanted sciatic nerves in which axonal transport was
      interrupted by crushing. We conclude that HO-2 is ubiquitous in perikarya of
      postganglionic sympathetic neurones, is subjected to axonal transport but does
      not accumulate at sympathetic neuroeffector junctions. This distribution favours
      a general role of HO-2 in sympathetic neuronal metabolism rather than a specific
      association with transmission at autonomic neuroeffector junctions.

PMID- 8742446
TI  - Spatial and non-spatial learning in the rat following lesions to the nucleus
      locus coeruleus.
AB  - The present experiment examined the effects of unilateral or bilateral locus
      coeruleus lesions on general activity, acquisition of a non-monotonic serial
      pattern (14-0-3-7 food pellets, respectively), and response learning acquisition
      in a Greek cross version of the Morris water maze. Sham-operated control rats
      were capable of tracking the elements of the serial pattern while rats with a
      unilateral locus coeruleus lesion were moderately impaired, and those with
      bilateral locus coeruleus lesions were severely impaired. A similar pattern of
      working memory deficits emerged in an analysis of the response-learning data in
      the Greek cross. The results are discussed in terms of the current understanding
      of norepinephrine and the locus coeruleus in learning and memory processes.

PMID- 8742447
TI  - Place-independent behavioural correlates of hippocampal neurones in rats.
AB  - The broad diversity of discharge correlates of hippocampal neurones has provoked
      controversy. For example, purported behavioural correlates could, instead, be
      location selectivity (of 'place cells') that is secondarily modulated by sensory
      stimulation or ongoing movements. In rats trained to perform identical behaviours
      in four corners of a symmetrical arena, we found hippocampal pyramidal cells
      discharged selectively as the rats performed task-related behaviours regardless
      of spatial location. Since the ensemble of these hippocampal neurones
      comprehensively represented all stages of the task, we propose that each cell
      represents an element of the temporal organization of the animal's behaviour,
      complementing the place cell representations of elements of the structure of the
      environment.

PMID- 8742448
TI  - Retarded vestibular compensation in mutant mice deficient in delta 2 glutamate
      receptor subunit.
AB  - The delta 2 subunit of ionotropic glutamate receptors is expressed only in the
      cerebellar Purkinje cell. In mutant mice deficient in the delta 2 protein,
      cerebellar long-term depression and motor coordination are impaired. We examined
      behavioural plasticity in these mutant mice after unilateral vestibular
      destruction. After intratympanic injection of sodium arsanilate, the mice showed
      roll head tilt and their righting response under a rotation load was impaired.
      These symptoms improved with time. However, compensation of the righting response
      was retarded in the mutant mice. These results suggest that motor learning of the
      delta 2 mutant mice is disturbed, and that the static and dynamic components of
      vestibular compensation may be controlled by different neuronal mechanisms.

PMID- 8742449
TI  - Expression of mGluR1 alpha mRNA receptor in rat and guinea pig cochlear neurons.
AB  - Glutamate or a parent substance is thought to be the afferent neurotransmitter in
      the auditory system. In situ hybridization showed that mGluR1 alpha mRNA was
      expressed by type I and type II spiral ganglion neurons in the cochlea. The glial
      cells surrounding the type I spiral ganglion neurons lacked such expression. The
      hybridization signal was low compared to that reported for non-NMDA receptors,
      suggesting that mGluR1 alpha receptors, as is the case for NMDA receptors, play a
      minor role in auditory transmission. The uniform expression of mGluR1 alpha mRNAs
      along the cochlear spiral suggests their co-expression in spiral ganglion neurons
      with NMDA and non-NMDA receptors and thus functional cooperation.

PMID- 8742450
TI  - Olfactory experience modulates Bcl-2 expression in the developing olfactory bulb.
AB  - The effect of olfactory deprivation on cellular expression of the Bcl-2 gene in
      the olfactory bulb of young rats was investigated. Restriction of olfactory
      stimuli caused an overall increase in Bcl-2 mRNA expression, with increases seen
      in the lateral aspects of glomerular, external plexiform, mitral and granule cell
      layers, as well as the medial aspects of external plexiform layer. No differences
      were found in the unoperated control group. In addition, we found an inverse
      relationship between the incidence of apoptosis induced by olfactory deprivation
      and the magnitude of increase in Bcl-2 mRNA expression in the glomerular layer.
      These data raise the possibility that Bcl-2 may be involved in olfactory
      experience-related neural plasticity by regulating cell survival.

PMID- 8742451
TI  - Lesions of area 17 in newborn kittens cause selective changes in the development
      of area 18.
AB  - In the cat, areas 17 and 18 interconnect soon after birth. To test the hypothesis
      that the normal development of area 18 depends on interactions with area 17,
      unilateral lesions of area 17 were created in newborn kittens, and the animals
      allowed to mature. Horseradish peroxidase was then injected into both lateral
      geniculate nuclei. The major abnormalities of area 18 in the lesioned hemispheres
      were a thinning of specifically layers 2 and 3 and abnormally faint
      geniculocortical labelling of layer 4. Cell densities in layers 2 and 3 of the
      lesioned hemispheres were similar to or lower than normal. Neonatal destruction
      of area 17 therefore produced a selective loss of cells in layers 2 and 3 in area
      18 (the layers that normally interconnect with area 17), and may have reduced
      thalamic innervation of layer 4.

PMID- 8742452
TI  - Apolipoprotein E gene expression in astrocytes: developmental pattern and
      regulation.
AB  - Apolipoprotein E (ApoE) is involved in brain development and repair. In order to
      investigate the contribution of astrocytes to ApoE gene expression, we
      investigated ApoE mRNA levels in mouse brain and in astroglial primary cultures
      during postnatal development and in two different trauma models. A biphasic
      developmental pattern was observed consisting in an increased expression during
      the first 2 weeks and a decrease in the later stages. A similar pattern was
      obtained in highly enriched primary cultures, suggesting ApoE mRNA location in
      the astroglial population and an important role for ApoE in astroglial
      development and/or function. ApoE gene expression could be modulated in culture
      by administration of lipopolysaccharides (LPS) which mimics a bacterial
      infection, or in reactive astrocytes consequent to a chemically induced lesion,
      suggesting that ApoE might be involved in the inflammatory events consequent to
      both situations. These results underline the importance of astrocytes in
      regenerative processes.

PMID- 8742454
TI  - Changes in alertness are a principal component of variance in the EEG spectrum.
AB  - Minute-scale fluctuations in the normalized EEG log spectrum, when correlated
      with concurrent changes in level of performance on a sustained auditory detection
      task, showed that a single principal component of EEG spectral variance is
      linearly related to minute-scale changes in detection performance. The particular
      EEG frequencies at which this coupling is expressed are similar for most subjects
      under a range of task conditions, and match those recently reported from analysis
      of verbal self-reports during drowsiness. The one-dimensional relationship
      between detection performance and the EEG spectrum confirms quantitatively the
      intuitive assumption that minute-scale changes in behavioral alertness during
      drowsiness are predominantly linked to changes in global brain dynamics along a
      single dimension of psychophysiological arousal.

PMID- 8742453
TI  - Morphine phase-shifts circadian rhythms in mice: role of behavioural activation.
AB  - The effect of morphine on circadial wheel-running rhythms of C57BL/6j mice was
      examined. Mice received morphine (25 mg kg-1, i.p.) or saline at eight different
      circadian phases in constant dark. Morphine injections in the middle of the
      inactive period induced significant advance phase shifts, whereas injections at
      other times induced small delay shifts or no responses. This phase-response
      relationship was not altered by optic enucleation. Morphine also induced
      hyperactivity. Restriction of activity prevented phase shifts. The results
      indicate that morphine shifts circadian rhythms by its effects on behaviour,
      rather than by a direct action on the circadian pacemaker. Morphine may represent
      a useful tool for further study of behaviourally induced phase-resetting in this
      species.

PMID- 8742455
TI  - High levels of amyloid-beta protein from S182 (Glu246) familial Alzheimer's
      cells.
AB  - Most early-onset familial Alzheimer disease is associated with missense mutations
      in S182, a membrane protein on chromosome 14. We investigated amyloid-beta
      protein (A beta) precursor (A beta PP) metabolism in skin fibroblasts from S182
      (Glu246)-affected individuals and unaffected family members. Steady-state A beta
      PP levels were similar among all lines as was the degree of increase in soluble A
      beta PP released upon stimulation of cells with either phorbol ester or serum.
      Among all lines studied, A beta levels were consistently detectable only in the
      medium of a single line of S182 (Glu246) cells, consistent with the conclusion
      that some S182 mutant lines may accumulate A beta in their conditioned media.
      Studies of cells from additional individuals and under other conditions will be
      required to establish this association of elevated A beta levels with S182
      mutations.

PMID- 8742456
TI  - The temporal lobes, reversed asymmetry and the genetics of schizophrenia.
AB  - Mechanisms determining temporal lobe structural asymmetries may be involved in
      the pathogenesis of schizophrenia. To investigate the temporal lobes in familial
      schizophrenia, computed tomographic scans were obtained from 51 subjects (seven
      families). Enlargement of sylvian fissures and temporal lobe sulcal spaces was
      observed in family members with schizophrenia. The posterior one-third of the
      sylvian fissure was larger on the left side in subjects with schizophrenia, and
      larger on the right side in unaffected individuals. This disturbed pattern of
      posterior sylvian fissure asymmetry suggests that adjacent language regions may
      be affected in schizophrenia. An intermediate degree of disturbance in subjects
      who had schizophrenia-related illnesses or were obligate carriers suggests that
      genetic factors may be important determinants of temporal lobe asymmetries in
      familial schizophrenia.

PMID- 8742457
TI  - Deafness-induced plasticity in the mature central auditory system.
AB  - Studies in rats and guinea pigs indicate that local changes in inhibitory
      transmitters may underlie deafness-induced plastic changes in
      electrophysiological responsiveness of cells of the mature central auditory
      system. Following 21 days of bilateral deafness there is an increase in evoked
      Fos-immunoreactive neurones in the central nucleus of the inferior colliculus
      (CIC) to contralateral cochlear electrical stimulation, compared with normal or 1
      day deafened animals. Deafness is also associated with a dramatic reduction in
      the population of CIC neurones that respond with suppression of activity to
      electrical stimulation. Moreover, in vivo microdialysis reveals a marked decrease
      in gamma-aminobutyric acid (GABA) release from the CIC cells in deafened animals.
      The results may have general implications for the mediation of central nervous
      system plasticity induced by deafferentation of sensory input.

PMID- 8742458
TI  - Mechanisms for sensory adaptation in frog vestibular organs.
AB  - The effects of external low-Ca, high-Mg solutions were tested both on frog
      isolated semicircular canals and on single cells isolated from these sensory
      organs. Our results showed that these media were able to cancel slow adaptation
      of the ampullar microphonic current in the whole organ and to abolish a Ca
      dependent K current (IK(Ca)) in single hair cells, suggesting that IK(Ca) is
      involved in vestibular sensory adaptation.

PMID- 8742459
TI  - Depolarizing stimuli induce high levels of dopamine synthesis in fetal rat
      sensory neurons.
AB  - To investigate the role of activity-dependent mechanisms in sensory transmitter
      development, we examined the effect of depolarizing stimuli on tyrosine
      hydroxylase expression and dopamine synthesis in cells of the fetal rat petrosal
      ganglion, a model of catecholaminergic sensory neurons. Although dopaminergic
      traits are normally detectable in only 10-20% of ganglion neurones, exposure to
      depolarizing concentrations of potassium chloride (40 mM) or veratridine (10
      microM) in culture induced tyrosine hydroxylase expression in 100% of petrosal
      neurons and a 10-fold increase in dopamine content. Tyrosine hydroxylase
      expression remained elevated in a subset of neurons following return to control
      conditions, suggesting that chronic depolarization elicits a phenotypic switch in
      some cells. These data show for the first time that transmitter expression in
      developing sensory neurons can be regulated by activity-related cues.

PMID- 8742460
TI  - Neonatal treatment with 5-HT antiserum alters 5-HT metabolism and function in
      adult rats.
AB  - Adult rats were studied for serotonin and its metabolite in basal ganglia,
      nociceptive responses to electric current and tremor induced by 5-methoxy-N,N
      dimethyltryptamine (5-MeODMT) to assess the effects of a single systemic
      injection of serotonin antiserum given at 1 day old. Antiserum-treated animals
      showed no overt behavioural abnormalities, but tremor induced by 5-MeODMT was
      augmented. Basal nociceptive thresholds for tail withdrawal and vocalization were
      unaffected, whereas vocalization after-discharge was significantly reduced.
      Significantly decreased serotonin levels and increased turnover were found in
      nucleus caudatus putamen, nucleus accumbens and tuberculum olfactorium of adult
      rats treated as neonates with serotonin antiserum. These results demonstrate long
      lasting functional alterations and neurochemical suppression of the central
      serotoninergic system following neonatal administration of serotonin antiserum.

PMID- 8742461
TI  - The P300 to novel and target events: a spatiotemporal dipole model analysis.
AB  - It has been reported that frontal lobe structures are critical for the generation
      of P300 activity in the human event-related potential (ERP) evoked by novel
      events. In this study spatial-temporal dipole model analyses were employed to
      obtain further evidence on the temporal dynamics and the approximate location of
      neuronal activity involved in P300 generation for target and novel events. A
      triple dipole configuration was found to describe the scalp recorded P300
      activity for novel and target events with less than 2.5% residual variance. For
      the novel, but not the target dipole configuration a frontally oriented dipole
      was obtained whose temporal activity function suggests that the brain areas
      involved in the processing of novel events are engaged about 70 ms earlier than
      those relevant for target processing.

PMID- 8742462
TI  - The intention to act improves unilateral left neglect: two demonstrations.
AB  - Unilateral neglect involves a spatial bias to one side of space, usually to the
      right. Perceptual and motor systems interact in the manifestation of this
      disorder, and there is also evidence that motor manipulative responses may have
      access to unique streams of information not available for non-motoric judgements.
      It is therefore predicted that the manifestation of neglect may be alterable by
      changing the purpose of otherwise very similar responses to spatially extended
      objects. In Experiment 1, neglect-based deviation to the right of centre was
      significantly less when subjects reached towards metal rods as if to pick them up
      in the centre, compared to when they pointed to their centres. In Experiment 2,
      subjects pointed to the centre of a rectangular box with a swivelled lid. They
      were then asked to place a coin at the centre of this lid, in a position
      sufficiently central to prevent the lid tilting and the coin falling into the
      box; in fact, the lid was fixed and subjects never received feedback. Responses
      were significantly more central with the balancing response than with the
      pointing one. These results suggest that prehensive movements towards objects
      allow 'leakage' of information about their spatial extent, via an unaffected
      stream of information available for motor-manipulative responses.

PMID- 8742463
TI  - Functional brain maps of retrieval mode and recovery of episodic information.
AB  - Positron emission tomography (PET) was used to identify brain regions associated
      with two component processes of episodic retrieval; those related to thinking
      back in subjective time (retrieval mode) and those related to actual recovery of
      stored information (ecphory). Healthy young subjects recognized words that had
      been encoded with respect to meaning or the speaker's voice. Regardless of how
      the information had been encoded, recognition was associated with increased
      activation in regions in right prefrontal cortex, left anterior cingulate, and
      cerebellum. These activations reflect retrieval mode. Recognition following
      meaning encoding was specifically associated with increased activation in left
      temporal cortex, and recognition following voice encoding involved regions in
      right orbital frontal and parahippocampal cortex. These activations reflect
      ecphory of differentially encoded information.

PMID- 8742464
TI  - Effect of the CCKA antagonist devazepide on eating stimulated by raphe injection
      of 8-OH-DPAT.
AB  - Several recent studies have suggested that feeding suppression is mediated
      jointly by enhanced neurotransmission of cholecystokinin (CCK) and serotonergic
      (5-HT) systems. In the present study the CCKA receptor antagonist devazepide (50
      200 micrograms kg-1, s.c.) was found reliably to potentiate the feeding response
      elicited by dorsal or median raphe injection of the 5-HT1A agonist 8-OH-DPAT (0.2
      0.8 nmol). This effect was evident following co-administration of both feeding
      threshold and subthreshold doses of either compound, suggesting that the
      simultaneous suppression of CCK and 5-HT function may interact as joint effectors
      of overeating.

PMID- 8742465
TI  - Crucial role of ecto-5'-nucleotidase in differentiation and survival of
      developing neural cells.
AB  - ATP, an important signalling substance in the central nervous system, is
      hydrolysed to adenosine via a surface-located enzyme cascade. The final
      hydrolysis step from AMP to adenosine is catalysed by 5'-nucleotidase, a GPI
      anchored surface protein. 5'-Nucleotidase is transiently expressed on developing
      neurones. An antisense oligonucleotide that suppresses the synthesis of 5'
      nucleotidase inhibits NGF-induced neurite formation and survival in PC12 cells
      and cultures of cerebellar granule cells. The inhibitory effect of the antisense
      oligonucleotide can be completely or partially relieved by addition of soluble 5'
      nucleotidase or of nucleosides to the medium. Our results suggest that 5'
      nucleotidase is essential for the differentiation and survival of neural cells
      and represents an important and critical step in the hydrolysis cascade of
      extracellular nucleotides.

PMID- 8742466
TI  - Descending noradrenergic neurones tonically suppress spinal presynaptic
      inhibition in rats.
AB  - We investigated the tonic depressant effect of descending noradrenergic neurones
      on spinal presynaptic inhibition. Presynaptic inhibition was measured in terms of
      the decrease in the amplitude of the monosynaptic reflex (MSR) evoked by
      conditioning stimulation of the adjacent dorsal root. This reduction in the MSR
      by conditioning stimulation was accompanied by primary afferent depolarization
      and was inhibited by the GABAA antagonist bicuculline, but not by the glycine
      antagonist strychnine. This presynaptic inhibition was much greater in spinalized
      rats than in intact rats, and was potentiated by the depletion of noradrenaline
      in the spinal cord in intact rats. These results suggest that presynaptic
      inhibition evoked by stimulation of the adjacent dorsal root seems to be
      tonically suppressed by descending noradrenergic neurones.

PMID- 8742467
TI  - Direct visual pathways for reaching movements in the macaque monkey.
AB  - The brain seems to process the location of objects faster than their intrinsic
      features, such as size, when these parameters are used to guide action. To
      uncover a potential anatomical substrate of these different processing speeds, we
      investigated in the monkey the pathways linking extrastriate visual cortex with
      the dorsal premotor area, a frontal area known to be involved in visually guided
      reaching movements. Retrogradely transported anatomical tracers were injected at
      physiologically defined sites and the distribution of labelled cells was examined
      in the ipsilateral cortex. We found a projection to the dorsal premotor cortex
      from the parieto-occipital area (PO). This area receives direct projections from
      the primary visual cortex (V1), and is part of the dorsal visual stream involved
      in the processing of spatial information. No direct projections to the dorsal
      premotor cortex arise from the ventral visual areas, thought to process object
      features. Our finding provides evidence for direct pathways from the dorsal
      visual stream to the dorsal premotor cortex and supports the view that the
      location of objects is processed faster by the brain than their intrinsic
      features.

PMID- 8742468
TI  - Oscillations for rapid selection of neural activities based on spike timing.
AB  - In cortical information processing, neuronal inputs are transformed into
      sequences of action potentials. However, the neural codes used for embedding
      information in the spike trains remain unclear. Here a neural network consisting
      of recurrent inhibitory connections is shown to achieve selective activation and
      inactivation of neurones very efficiently according to spike timing rather than
      firing rates, when they are stimulated by periodic spike trains. Oscillatory
      neural activities serve as an accurate clock for the spike-timing code utilized
      in the rapid selection of neural activities. These results suggest that
      differences in spike timing of < 1 ms can be of functional significance in
      certain neural information processing.

PMID- 8742469
TI  - Protein phosphorylation of synaptic membranes isolated from the brain of ground
      squirrels during hibernation.
AB  - In vitro protein phosphorylation of synaptic membranes isolated from neocortex
      and hippocampus of ground squirrels was studied. Three functional states of
      animals were investigated: torpid, awakened and active normothermic.
      Phosphorylation of a protein with a mol. wt of 53 kDa was independent on the
      functional state of the animals. Incorporation of 32P into this protein was
      greater in membranes of torpid and awakened squirrels than in membranes of active
      animals. These results suggest that protein phosphorylation is involved in the
      maintenance of membrane functions during hibernation.

PMID- 8742470
TI  - Brain stem energy metabolism response to acute hypoxia in anaesthetized rats: a
      31P NMR study.
AB  - Mammals react to acute hypoxia with an initial augmentation and a secondary
      depression of the respiratory rhythm generated by brain stem neuronal networks.
      To investigate the cytosolic level of energy rich phosphorus metabolites during
      these responses, we developed 31P nuclear magnetic resonance spectroscopy of the
      brain stem. Moderate hypoxia (paO2 = 40 mmHg, 2 min) caused a reversible 62 +/-
      15% respiratory rhythm depression and decreased cytosolic phosphocreatine levels
      by 43 +/- 11% (p < 0.01, n = 7) without affecting adenosine triphosphate levels.
      Cellular metabolic depletion therefore contributes to the brain stem response to
      hypoxia, and appears to reflect adaptive mechanisms to limited oxygen
      availability in the brain stem.

PMID- 8742471
TI  - Measurement of circadian rhythms of ocular melatonin in the pigeon by in vivo
      microdialysis.
AB  - Ocular melatonin rhythms were measured in pigeons (Columba livia) by in vivo
      microdialysis. The birds were placed in light-dark cycles with 12 h of light and
      12 h of darkness (LD12:12) or continuous dim light (LLdim) after LD12:12. Under
      LD12:12, melatonin levels were low during the light and high during the dark. The
      rhythms persisted under LLdim with lower levels during the subjective day and
      higher levels during the subjective night. Two hours of light exposure in the
      middle of the night acutely suppressed melatonin to the daytime level. These
      results indicate that microdialysis is useful for studies investigating the
      mechanism regulating ocular melatonin rhythms.

PMID- 8742472
TI  - Differential modulation of brain immediate early genes by intraperitoneal LiCl.
AB  - We have used in situ hybridization to investigate the modulation of expression of
      the immediate early genes (IEGs) c-fos, fos-B, zif/268 and CREM in rat brain
      following oral administration of saccharin, i.p. injection of LiCl, and
      conditioned taste aversion (CTA) training in which these stimuli are used as the
      conditioned stimulus (CS) and the unconditioned stimulus (UCS), respectively.
      Modulation of c-fos, zif/268 and CREM was detected in the NTS, PBN, hypothalamic
      PVN and central nucleus of the amygdala after the administration of the UCS but
      not the CS. Our data are consonant with the hypothesis that differential and
      combinatorial expression of IEGs plays a role in encoding the representation of
      LiCl-induced malaise in the brain.

PMID- 8742473
TI  - Differential expression of inducible nitric oxide synthase mRNA in human brain
      tumours.
AB  - Messenger RNA encoding the inducible form of human nitric oxide synthase (iNOS)
      was quantified by reverse transcription and polymerase chain reaction (RT-PCR) in
      tissue samples from glioblastomas and meningiomas. iNOS mRNA expression was
      considerably higher in the glioblastoma than in the meningioma specimens (mean +/
      s.e.m., 41.18 +/- 11.5, n = 25, vs 5.31 +/- 0.98, n = 21; p < 0.0001). Moreover,
      iNOS expression appeared as a polymorphic character among glioblastomas, as
      individual tumours expressed either high (n = 6), intermediate (n = 10) or low (n
      = 9) levels of iNOS mRNA.

PMID- 8742474
TI  - A mutation in Alzheimer's disease destroying a splice acceptor site in the
      presenilin-1 gene.
AB  - A series of mutations has been reported in the presenilin-1 (PS-1) gene which
      cause early onset Alzheimer's disease (AD). The mutations reported to date have
      encoded missense mutations which alter residues conserved between PS-1 and the
      presenilin-2 (PS-2) gene. We have recently determined the intron/exon structure
      of the PS-1 gene and this information has been used to identify a mutation in the
      splice acceptor site for exon 9 in a family with early onset AD. Amplification of
      cDNA from lymphoblasts of affected individuals revealed that the effect of the
      mutation was to cause splicing out of exon 9, however it does not change the open
      reading frame of the mRNA. The importance of this observation is discussed.

PMID- 8742475
TI  - Hypothermia preserves expression of beta-actin mRNA in ischemic brain.
AB  - The expression of a cytoskeletal protein, beta-actin, mRNA was examined in
      hypothermic ischemic brains. Mongolian gerbils were subjected to forebrain
      ischemia by bilateral carotid occlusion of 10 min at 30 degrees C followed by
      normothermic reperfusion for 1 h or 6 h, 1 day or 3 days, 2 weeks or 1 month. The
      expression of beta-actin mRNA was determined in hypothermic controls and
      postischemic (PI) animals subjected to intra-ischemic hypothermia using in situ
      hybridization. On comparing the pattern of expression of beta-actin in
      hypothermic ischemic brains with that in normothermic ischemic brains, it was
      noted that there was no significant decline in its expression in the CA1 region
      of hypothermic ischemic brains as noted in the normothermic ischemic brains
      (reported by us previously). Only one hypothermic ischemic animal in the 2 week
      PI period showed marked reduction in its expression in the CA1 region. These
      results indicate that hypothermia leads to preservation of the expression of a
      cytoskeletal protein, beta-actin, in a selectively vulnerable region of the brain
      following ischemia.

PMID- 8742476
TI  - Prefrontal neurones sensitive to increased visual attention in the monkey.
AB  - Single units were recorded in the prefrontal cortex of two monkeys performing a
      simple visual detection task. Task difficulty was manipulated in consecutive
      blocks of trials to increase the degree of attention towards the stimulus.
      Fifteen percent of the neurones sampled exhibited a systematic change in the
      average preparatory discharge rate in relation to task difficulty. Behavioural
      data (changes in reaction time and error ratios, 'difficult' probe trials
      presented in the 'easy' context) suggested that increased attention was actually
      induced. These results show the sensitivity of a population of prefrontal
      neurones to the behavioural context which determine the level of attention. The
      preparatory nature of the observed changes may be of special functional
      significance for the control of effortful attention.

PMID- 8742477
TI  - Reactive astrocytes express substance-P immunoreactivity in the adult forebrain
      after injury.
AB  - Transformation of normal resting astrocytes to reactive astrocytes after injury
      is a well-known phenomenon. Using immunofluorescent labelling methods, astrocytes
      in the ischemically and retrogradely/anterogradely damaged adult forebrain nuclei
      were shown to express substance-P immunoreactivity. In contrast, astrocytes were
      not immunostained for substance-P in the normal brain or undamaged areas. Since
      substance-P has been shown to regulate inflammatory, wound-healing and immune
      responses in the peripheral tissues, it is likely that this aberrant expression
      of substance-P immunoreactivity in reactive astrocytes may relate to similar
      functions in the central nervous system as in the peripheral tissues after
      injury.

PMID- 8742478
TI  - Electrical stimulation of the vagus nerve modulates the histamine content of mast
      cells in the rat jejunal mucosa.
AB  - Mast cells are best known for their participation in allergic reactions. However,
      a number of recent studies suggest that mast cells are subject to nervous
      control. In the gut mucosa, mast cells are intimately associated with nerves, and
      the psychologically conditioned release of RMCP II (a mucosal mast cell-derived
      mediator) has been reported. These data suggest the potential for CNS regulation
      of intestinal mucosal mast cells. In this study, we stimulated the cervical vagi
      and found an increased histamine content in mucosal mast cells, without apparent
      degranulation. Furthermore, these changes could be prevented by subdiaphragmatic
      vagotomy. These data support the potential for intestinal mucosal mast cell
      regulation by the central nervous system and suggest modulation of mast cells
      without degranulation.

PMID- 8742479
TI  - Immunohistochemical localiztion of homocysteate in human primary visual cortex.
AB  - Polyclonal and monoclonal anti-homocysteate antibodies were used with a
      postembedding immunohistochemical method for light microscopy to localize
      homocysteate-like immunoreactivity in human primary visual cortex. Densely
      accumulated dots of diverse size resembling astrocytic processes were labelled in
      supragranular layers, mainly in layers I and II. Some glial elements intermingled
      with fibre bundles in the white matter, and astrocytic endfeet in the vicinity of
      capillaries were also stained. In addition, very few round or elongated neuronal
      cell bodies in layer IVc were intensely homocysteate immunoreactive. These
      observations extend to human primary visual cortex previous studies on the
      preferential localization of L-homocysteate in glia.

PMID- 8742480
TI  - fMRI of human somatosensory and cingulate cortex during painful electrical nerve
      stimulation.
AB  - Functional MRI (fMRI) can detect changes from resting levels of blood flow and
      oxygenation during task performance (i.e. activation). We used a simple
      electrical nerve stimulation technique together with fMRI to study pain process
      in the human cortex. Images of the primary somatosensory (SI) and cingulate
      cortex (Cg) were obtained from subjects during stimulation at painful and non
      painful intensities. Stimuli that evoked non-painful tingling sensations
      activated the contralateral SI but not Cg. Stimuli that evoked painful sensations
      activated both the contralateral SI and Cg. These data indicate that fMRI can
      detect pain-related changes in SI and Cg evoked by electrical stimulation of
      peripheral nerves. These findings add to the evidence for a role of SI and Cg in
      human pain processes and provide a simple method of stimulus delivery for its
      study.

PMID- 8742481
TI  - The post-translational incorporation of arginine into a beta-amyloid peptide
      increases the probability of alpha-helix formation.
AB  - The beta-amyloid peptide (beta AP1-40) inhibited the in vitro post-translational
      incorporation of [14C]arginine at the N-terminus of brain soluble proteins and
      was labelled by the incorporation of [14C]arginine. Addition of arginine at the N
      terminal position of beta AP1-40 is predicted to increase the probability of an
      alpha-helix structure being formed on the first residues with a higher
      hydrophilic characteristic, increasing the possibility of these residues being
      exposed to the aqueous environment. Unmodified beta AP1-40 has a low alpha-helix
      content and a higher probability of beta-turn formation. Accumulation of beta AP1
      40 in Alzheimer's disease may therefore be due to a reduced arginylation reaction
      and consequently to a decrease in its normal degradation by the ubiquitin
      pathway.

PMID- 8742482
TI  - Nicotine withdrawal leads to increased firing rates of midbrain dopamine neurons.
AB  - In order to explore the neurophysiology of nicotine withdrawal, we examined the
      activity of substantia nigra (A9) and ventral tegmental area (A10) dopamine cells
      in rats undergoing withdrawal from chronic exposure to nicotine. Animals were
      exposed to nicotine (6 mg kg-1 day-1 base) via s.c. implanted osmotic minipumps.
      After 12 days the pumps were removed and the animals allowed to go through
      spontaneous withdrawal. Rats were anesthetized on various days of the procedure
      and single-unit recordings were made from A9 and A10 dopamine cells. Chronic
      administration of nicotine led to a decreased firing rate of A10, but not A9,
      dopamine cells. Upon withdrawal from the chronic exposure to nicotine, the firing
      rates of A10 dopamine cells returned to control levels, while the firing rate of
      A9 dopamine cells significantly increased above control levels. This increased
      dopamine neuronal activity may play a role in some behavioural symptoms of
      nicotine withdrawal.

PMID- 8742483
TI  - Modulation of mouse cerebral Na+,K(+)-ATPase activity by oxygen free radicals.
AB  - There is increasing evidence that oxygen free radicals (OFR) are involved in
      cerebral ischaemia-reperfusion injury, possibly via a modulation of Na+,K(+)
      ATPase activity, one of the major membrane pumps responsible for ionic
      homeostasis. We measured OFR-mediated modulation of this enzymatic activity and
      examined the roles of lipid and/or protein alterations. Using mouse brain
      microsomes exposed to UV-C irradiation, our results show a good correlation
      between activity inhibition and lipoperoxidation estimated by PUFA loss as well
      as malondialdehyde production. The protective effect of thiourea (OH scavenger)
      and the lack of effect noted with DTT (thiol protector) suggest that the
      functionality of the Na+,K(+)-ATPase is altered by perturbation of membrane
      integrity rather than by a structural alteration of the protein itself.

PMID- 8742484
TI  - Expression of GAP-43 mRNA in preganglionic sympathetic neurones of the adult rat
      spinal cord.
AB  - In situ hybridization combined with intraperitoneal injection of the tracer
      Fluoro-Gold was used to study the distribution of GAP-43 mRNA in autonomic cell
      groups of the rat spinal cord. In the thoracic cord, numerous cells expressing
      GAP-43 mRNA were present in the central autonomic nucleus (lamina X) and in the
      intermediolateral cell column (IML). In the IML, all Fluoro-Gold-labelled
      preganglionic neurones were heavily labelled for GAP-43 mRNA. In contrast, Fluoro
      Gold-labelled motoneurones were unlabelled or only lightly labelled. Our results
      indicate that preganglionic sympathetic neurones express GAP-43, a conclusion
      that is consistent with studies showing that GAP-43 immunoreactive terminals are
      present in autonomic ganglia. GAP-43 in these neurones may play a role in their
      continuing anatomical remodelling.

PMID- 8742485
TI  - Human astrocytoma cells express a unique chloride current.
AB  - Human astrocytoma cells were studied using whole-cell patch-clamp recording.
      Voltage-dependent outwardly-rectifying anion currents were identified in primary
      cultures of six freshly resected human brain tumors and in seven established
      anaplastic astrocytoma/glioblastoma cell lines (U251MG, CH235MG, U373MG, U105MG,
      D54MG, SK-MG-1, and STTG1). Anion currents were not observed in normal, non
      neoplastic glial cells, nor in human tumor-derived cells of non-glial origin
      (melanoma, breast cancer, neuroblastoma, rhabdomyosarcoma). Currents activated at
      potentials > 50 mV and showed large transients upon termination of voltage steps.
      Currents reversed at the predicted equilibrium potential for chloride ions and
      could also be recorded when Cl- was replaced by F-, Br- or I-. Currents were
      inhibited by the Cl- channel blockers chlorotoxin, DIDS, and DNDS. These Cl-
      currents may play a role in the growth control of astrocytoma cells.

PMID- 8742486
TI  - GDNF protects against 6-OHDA nigrostriatal lesion: in vivo study with
      microdialysis and PET.
AB  - We have investigated whether glial cell line-derived neurotrophic factor (GDNF)
      protects against a complete unilateral 6-hydroxydopamine (6-OHDA) nigrostriatal
      lesion, a robust rat model of Parkinson's disease. GDNF or vehicle were
      administered above the rat substantia nigra and into the lateral ventricle
      immediately before an ipsilateral 6-OHDA injection into the medial forebrain
      bundle. In vivo tests were employed to assess the effects of the treatment:
      microdialysis to measure striatal dopamine release, amphetamine challenge to
      estimate turning behaviour, and positron emission tomography (PET) to image
      dopamine reuptake sites. The present results show that GDNF can protect
      dopaminergic neurones against an acute and irreversible 6-OHDA lesion. They are
      encouraging for potential use of GDNF in Parkinson's disease.

PMID- 8742487
TI  - Regulation of [3H]5-HT release in raphe, frontal cortex and hippocampus of 5-HT1B
      knock-out mice.
AB  - Regulation of the electrically evoked release of [3H]5-HT was examined in
      midbrain, frontal cortex and hippocampus preloaded slices obtained from wild-type
      and 5-HT1B knock-out mice. In the absence of any drug [3H]5-HT released was
      increased in midbrain and hippocampus but not in frontal cortex slices of [3H]5
      HT1B knock out mice. The selective 5-HT1B agonist CP 93129 and the 5-HT1B/1D
      agonist sumatriptan, inhibited [3H]5-HT release in hippocampus and cortical
      slices obtained from control mice but had no effect in mutants. In the two
      projection areas studied, the non-selective 5-HT agonist 5-carboxyamidotryptamine
      (5-CT) inhibited [3H]5-HT release in both groups of mice, indicating that
      additional 5-HT receptors, other than 5-HT1B, might be involved in the regulation
      of [3H]5-HT release from 5-HT terminals. In slices containing midbrain raphe
      nuclei, CP 93129 had no effect in either group. In contrast, sumatriptan
      inhibited [3H]5-HT release in controls and mutants. The latter effect was blocked
      by the 5-HT1D antagonist GR 127935, but not the 5-HT1A antagonist (+)WAY 100135,
      thus suggesting that a 5-HT1D-like receptor, possibly 5-HT1D alpha, negatively
      regulates 5-HT release in mouse midbrain raphe nuclei.

PMID- 8742488
TI  - Haloperidol-induced cell death--mechanism and protection with vitamin E in vitro.
AB  - Haloperidol, a dopamine receptor antagonist and sigma-receptor-active neuroleptic
      drug, is cytotoxic to primary hippocampal neurones, C6 glioma cells and NCB20
      cells. A 24 h challenge of these cells with haloperidol resulted in reduced cell
      viability and ultimately cell lysis. The most dramatic changes in cellular
      morphology were the retraction of cellular extensions, development of membrane
      blebs, and finally cell detachment from the culture dish. DNA isolated from
      haloperidol-treated cells was randomly degraded, indicating a necrotic rather
      than an apoptotic pathway of cell death. Vitamin E (alpha-tocopherol), a
      lipophilic free radical scavenger, prevented haloperidol-induced DNA
      fragmentation and ultimately cell death. These findings suggest that haloperidol
      induces necrotic cell death in which free radicals play a major role.

PMID- 8742489
TI  - Early regional changes of GFAP mRNA in rat hippocampus and dentate gyrus during
      soman-induced seizures.
AB  - We investigated the time course of GFAP levels in the hippocampal formation
      during the first 24 h following soman intoxication in rats. GFAP mRNA expression
      was detected by in situ hybridization. Intense GFAP mRNA expression was present
      in the molecular layer of the dentate gyrus as early as 6 h after intoxication.
      This expression was comparatively lower in other dentate gyrus layers and
      hippocampal CA1, CA3 and CA4 areas and seemed to be related to excessive neuronal
      activity. Histopathological examination demonstrated that GFAP expression in
      dentate gyrus is not correlated with lesions. The high astrocytic reactivity in
      the molecular layer of the dentate gyrus is discussed in relation to the
      maintenance of the homeostasis of glutamate and of synaptic plasticity in this
      area during soman intoxication.

PMID- 8742490
TI  - Gravity and hemineglect.
AB  - Spatial cognition requires the integration of visual inputs with proprioceptive
      and vestibular information about the position of the eye, the head and the body.
      All these sources are used by the brain to produce multiple higher-order (e.g.
      egocentric) representations of space, subserving accurate spatial behaviour. Such
      spatial representations are disrupted by unilateral cerebral damage producing
      neglect in the contralateral side of space. In eight brain-damaged patients with
      left unilateral neglect the manipulation of gravitational-otolithic information,
      obtained by placing patients in a supine position, produced a significant
      reduction of the rightward directional error in the line bisection task in all
      cases. This finding suggests that, in patients with neglect, gravitational
      information is processed in a non-symmetrical fashion, with a rightward bias
      towards the side of the lesion. This is the first study showing that manipulation
      of gravitational input affects neuropsychological disorders of visuo-spatial
      processing.

PMID- 8742491
TI  - Specific and efficient gene transfer strategy offers new potentialities for the
      treatment of motor neurone diseases.
AB  - Several growth factors are candidates for the therapy of motor neurone diseases.
      However, there is no efficient, safe, and practicable administration route which
      hampers the clinical use of these potentially therapeutic agents. We show that
      specific and high yield gene transfer into motor neurones can be obtained by
      peripheral intramuscular injections of recombinant adenoviruses. These vectors
      are retrogradely transported from muscular motor units to motor neurone cell
      bodies. Gene transfer can thus be specifically targeted to particular regions of
      the spinal cord by appropriate choice of the injected muscle. The efficiency of
      gene transfer is high, with 58-100% of the motor neurones afferent to the
      injected muscle expressing the transgene. This new therapeutic protocol allows
      specific targeting of motor neurones without lesioning the spinal cord, and
      should avoid undesirable side effects associated with systemic administration of
      therapeutic factors.

PMID- 8742492
TI  - Identifiable Achatina giant neurones: their localizations in ganglia, axonal
      pathways and pharmacological features.
AB  - 1. An African giant snail (Achatina fulica Ferussac), originally from East
      Africa, is now found abundantly in tropical and subtropical regions of Asia,
      including Okinawa in Japan. This is one of the largest land snail species in the
      world. The Achatina central nervous system is composed of the buccal, cerebral
      and suboesophageal ganglia. The 37 giant neurones were identified in these
      ganglia by the series of studies conducted over about 20 years. The
      identifications were made by the localization of these neurones in the ganglia,
      their axonal pathways and their pharmacological features. 2. In the left buccal
      ganglion, the four giant neurones, d-LBAN, d-LBMB, d-LBCN and d-LBPN, were
      identified. In the left and right cerebral ganglia, d-LCDN, d-RCDN, v-LCDN and v
      RCDN were identified. The suboesophageal ganglia are further composed of the left
      and right parietal, the visceral, the left and right pleural, and the left and
      right pedal ganglia. In the right parietal ganglion, PON, TAN, TAN-2, TAN-3,
      RAPN, d-RPLN, BAPN, LPPN, LBPN, LAPN and v-RPLN were identified. In the visceral
      ganglion, VIN, FAN, INN, d-VLN, v-VLN, v-VAN, LVMN, RVMN and v-VNAN were
      identified. In the left parietal ganglion, v-LPSN was identified. In the left and
      right pedal ganglia, LPeNLN, RPeNLN, d-LPeLN, d-LPeCN, d-RPeAN, d-LPeDN, d-LPeMN
      and d-LPeEN were identified. 3. Of the small molecule compounds tested, dopamine,
      5-hydroxytryptamine, GABA, L-glutamic acid, threo- or erythro-beta-hydroxy-L
      glutamic acid were effective on the Achatina giant neurones. We suppose that
      these compounds act as the neurotransmitters for these neurones. 4. Of the
      neuroactive peptides, achatin-I(Gly-D-Phe-Ala-Asp). APGW-amide(Ala-Pro-Gly-Trp
      NH2) and Achatina cardioexcitatory peptide (ACEP-1)(Ser-Gly-Gln-Ser-Trp-Arg-Pro
      Gln-Gly-Arg-Phe-NH2) were proposed as neurotransmitters, because these were
      effective on the Achatina giant neurones and their presence was demonstrated in
      the Achatina ganglia. Further, myomodulin (Pro-Met-Ser-Met-Leu-Arg-Leu-NH2),
      buccalin (Gly-Met-Asp-Ser-Leu-Ala-Phe-Ser-Gly-Gly-Leu-NH2), FMRFamide (Phe-Met
      Arg-Phe-NH2). [Ser2]-Mytilus inhibitory peptide ([Ser2]-MIP) (Gly-Ser-Pro-Met-Phe
      Val-NH2), catch-relaxing peptide (CARP) (Ala-Met-Pro-Met-Leu-Arg-Leu-NH2),
      oxytocin (Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2) and small cardioactive
      peptideB (SCPB) (Met-Asn-Tyr-Leu-Ala-Phe-Pro-Arg-Met-NH2) could also be
      neurotransmitters because these peptides were also effective on the Achatina
      giant neurones, though their presence in the ganglia of this animal has not yet
      been demonstrated. 5. Calcium current (ICa) was recorded from Achatina giant
      neurones in the Na(+)-free solution containing K(+)-channel blockers under
      voltage clamp. The Ca2+ antagonistic effects of brovincamine, verapamil,
      eperisone, diltiazem, monatepil, etc., were compared using the ICa of the
      Achatina neurones. 6. Almost all of the mammalian small molecule
      neurotransmitters were effective on the Achatina giant neurones, suggesting that
      these compounds are acting on the neurones of a wide variety of animal species.
      However, the pharmacological features of the Achatina neurone receptors to these
      compounds were not fully comparable to those of the mammalian receptors. For
      example, we proposed that beta-hydroxy-L-glutamic acid (either threo- or erythro
      ) could be an inhibitory neurotransmitter for an Achatina neurone. 7. In
      contrast, the Achatina giant neurones appear to have no receptor for the
      mammalian neuroactive peptides, except for oxytocin and Arg-vasotocin. On the
      other hand, many neuroactive peptides were isolated from invertebrate nervous
      tissues, including achatin-I, a neuroexcitatory tetrapeptide having a D
      phenylalanine residue.

PMID- 8742493
TI  - G-protein-coupled receptors in HL-60 human leukemia cells.
AB  - 1. HL-60 human leukemia cells are a widely employed model system for the analysis
      of signal transduction processes mediated via regulatory heterotrimeric guanine
      nucleotide-binding proteins (G-proteins). HL-60 promyelocytes are pluripotent and
      can be differentiated into neutrophilic or monocytic cells. 2. HL-60 cells
      express formyl peptide-, complement C5a-, leukotriene B4 (LTB4)- and platelet
      activating factor receptors, receptors for purine and pyrimidine nucleotides,
      histamine H1- and H2-receptors, beta 2-adrenoceptors and prostaglandin receptors.
      3. The major G-proteins in HL-60 cells are pertussis toxin (PTX)-sensitive Gi
      proteins (Gi2 > Gi3). Gs-proteins and G-proteins of the Gq-family (e.g., G16) are
      expressed, too. 4. G-protein-regulated effector systems in HL-60 cells are
      adenylyl cyclase and phospholipase C-beta 2 (PLC-beta 2) and, possibly,
      phospholipase D (PLD), nonselective cation (NSC) channels and NADPH oxidase. 5.
      The expression of signal transduction pathways in HL-60 cells strongly depends on
      the differentiation state of cells. 6. Formyl peptides, via Gi-proteins, mediate
      activation of PLC, PLD, NSC channels, NADPH oxidase and azurophilic granule
      release and are referred to as full secretagogues. In dibutyryl cAMP (Bt2cAMP)
      differentiated HL-60 cells, C5a and LTB4 are partial and incomplete
      secretagogues, respectively. There are substantial differences in the Gi-protein
      activations induced by formyl peptides, C5a and LTB4. 7. In HL-60 promyelocytes,
      purine and pyrimidine nucleotides mediate activation of PLC and NSC channels
      largely via PTX-insensitive G-proteins and induce functional differentiation. In
      Bt2cAMP-differentiated HL-60 cells, they additionally activate PLD, NADPH oxidase
      and granule release via PTX-sensitive and -insensitive pathways. ATP and UTP are
      partial secretagogues. Multiple types of receptors (i.e., P2Y- and P2U-receptors
      and pyrimidinocyeptors) may mediate the effects of nucleotides in HL-60 cells. 8.
      Bt2cAMP- and 1 alpha,25-dihydroxycholecalciferol-differentiated HL-60 cells
      express H1-receptors coupled to Gi-proteins and PTX-insensitive G-proteins. In
      the former cells, histamine mediates activation of PLC and NSC channels, and in
      the latter, activation of NSC channels. Histamine is an incomplete secretagogue
      in these cells. 9. HL-60 promyelocytes express H2-receptors coupled to adenylyl
      cyclase, PLC, and NSC channels. There are substantial differences in the
      agonist/antagonist profiles of H2-receptor-mediated cAMP formation and rises in
      cytosolic Ca2+ concentration, indicative of the involvement of different H2
      receptor subtypes. H2-receptors mediate functional differentiation of HL-60
      cells. 10. Certain cationic-amphiphilic histamine receptor ligands (i.e., 2
      substituted histamines, lipophilic guanidines, and a histamine trifluoromethyl
      toluidide derivative) show stimulatory effects in HL-60 cells that are
      attributable to receptor-independent activation of Gi-proteins.

PMID- 8742494
TI  - Blood pressure regulation by the kallikrein-kinin system.
AB  - 1. The kallikrein-kinin system has a significant role in regulating arterial
      blood pressure. 2. Reduced formation of the kinin compontents may cause
      hypertensive diseases. This is because of the fact that this system is
      responsible for vasodilatation, reduction in total peripheral resistance,
      natriuresis, diuresis, increasing renal blood flow and releasing various
      vasodilator agents. 3. Reduced kinin-kallikrein generation in hypertensive
      subjects may also be associated with genetic and environmental defects. 4. The
      kallikrein-kinin system when administered to hypertensive patients can lower
      their raised blood pressure to normotensive levels. 5. The mode of action of
      angiotensin-converting enzyme inhibitors principally may be dependent on the
      kinin system protection.

PMID- 8742495
TI  - Unreliability of saliva samples for monitoring chloroquine and proguanil levels
      during anti-malarial chemoprophylaxis.

PMID- 8742496
TI  - Three distinct components of the negative inotropic action of lidocaine in dog
      Purkinje fiber.
AB  - 1. The negative inotropic action of 10 microM lidocaine and 100 microM nicorandil
      was compared as a function of the pacing cycle length, ranging from 300-3000 ms,
      in isolated canine Purkinje fiber preparations. 2. The applied concentrations of
      lidocaine and nicorandil produced similar shortening of action potential
      duration; however, lidocaine compromised contractility stronger than nicorandil
      at each cycle length. 3. Normalizing the inotropic action of the drugs to their
      shortening effect on action potential duration, the negative inotropic action of
      lidocaine can be regarded as a sum of three distinct components: negative
      inotropy associated to the shortening of action potential duration per se,
      reduction of contractility likely due to direct inhibition of the fast sodium
      current and of the "window" sodium current by lidocaine.

PMID- 8742497
TI  - Effects of a newly developed transdermal clonidine delivery system (M-5041T) on
      EEG sleep-wake cycle in relation to plasma concentration in rabbits.
AB  - 1. The effects of a transdermal clonidine delivery system (M-5041T) on EEG sleep
      pattern with relation to plasma concentrations in unrestrained rabbits were
      investigated and compared with those of intravenous (i.v.) administration of
      clonidine. 2. Although M-5041T did not affect the EEG recorded from cortex and
      hippocampus at doses up to 2.5 mg/kg, slow theta waves in hippocampal EEG
      accompanied by low-voltage slow waves in cortex were induced at a higher dose of
      12.5 mg/kg. On i.v. injection (0.25 mg/kg), EEG tracings with bursts of high
      voltage slow waves in cortical EEG and slow theta waves in hippocampus were
      observed. 3. At doses of 0.5 and 2.5 mg/kg, M-5041T did not cause any alterations
      of the sleep-wake cycle, and plasma concentrations of 1-2 ng/ml were maintained
      for an 8-hr observation period. However, this delivery system significantly
      suppressed the incidence of rapid-eye movement sleep (REMS) from 11.9 to 4.7% and
      enhanced drowsiness (DW) from 9.0 to 21.0% during the 8-hr recording period at
      12.5 mg/kg with a plasma concentration of up to 10 ng/ml. Contrary to transdermal
      administration, i.v. clonidine (0.25 mg/kg) completely blocked light and deep
      slow wave sleep as well as REMS with a plasma concentration indicated more than
      10 ng/ml at 2 hr post administration. Recovery to a normal sleep-wake cycle was
      eventually established thereafter. The incidence of REMS and DW were
      significantly decreased from 11.9 to 6.3% and increased from 9.0 to 25.5%,
      respectively. 4. Concurrent monitoring of clonidine concentrations in
      cerebrospinal fluid (CSF) indicated that CSF concentrations after patching M
      5041T, as well as i.v. clonidine, were almost equal to plasma levels. 5. These
      results suggest that alteration of the sleep-wake cycle with clonidine occurs
      depending upon brain concentrations, which increase to a level similar to that in
      plasma after administration, and that M-5041T at doses of less than 2.5 mg/kg
      could establish effective hypertensive therapy without obvious effects on the
      cycle.

PMID- 8742498
TI  - Influence of diet free of NAD-precursors on acetaminophen hepatotoxicity in mice.
AB  - Recently, we demonstrated the hepatoprotective effects of nicotinic acid amide, a
      selective inhibitor of poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30) on mice
      suffering from acetaminophen (AAP)-hepatitis, suggesting that the AAP-induced
      liver injury involves a step which depends on adenoribosylation. The present
      study investigates the effects of a diet free of precursors of NAD, the substrate
      on which PARP acts, in female NMRI mice with AAP hepatitis and evaluates the
      influence of simultaneous ethanol consumption in these animals. Liver injuries
      were quantified as serum activities of glutamate-oxaloacetate transaminase (GOT)
      and glutamate-pyruvate transaminase (GPT). While AAP caused a 117-fold elevation
      of serum transaminase activities in mice kept on a standard laboratory diet,
      which was significantly exacerbated by ethanol and inhibited by nicotinic acid
      amide (NAA), adverse effects were noted in animals fed a diet free of precursors
      of NAD. In these animals, only minor increases of serum transaminase activities
      were measured in the presence of AAP, and unlike the exacerbation caused by
      ethanol in mice on a standard diet, the liver damage was inhibited by 50% by
      ethanol. A further 64% reduction of hepatitis was observed, when NAA was given to
      ethanol/AAP-mice. Our results provide evidence that the AAP-induced hepatitis and
      its exacerbation by ethanol can either be reduced by end-product inhibition of
      PARP by NAA or by dietary depletion of the enzyme's substrate NAD. We see the
      main application of NAA as for the combinational use in pharmaceutical
      preparations of acetaminophen in order to avoid hepatic damage in patients
      treated with this widely used analgesic.

PMID- 8742499
TI  - Kainate produces concentration-dependent elevation of glutamate release but not
      cGMP levels in cultured neuron.
AB  - 1. Treatment of cultured cerebellar granule cells for 3 min with N-methyl-D
      aspartate (NMDA) resulted in a concentration-dependent elevation of cyclic GMP.
      However, neither kainate (KA) nor NMDA produced a concentration-dependent
      elevation of this nucleotide after exposing cells to the agonist for 60 min. 2.
      Unlike the case for cGMP, both KA and NMDA produced concentration-dependent
      elevations of glutamate for 60 min incubation. 3. The NMDA-induced elevations of
      cGMP and glutamate were blocked by selective NMDA receptor antagonists. 4. The
      selective KA/alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor
      antagonist, 6,7-nitroquinoxaline-2,3-dione (DNQX), blocked the KA-induced
      elevations of cGMP with 3-min exposures, but it augmented the response with 60
      min exposures. However, the KA-induced release of glutamate was prevented by
      DNQX. 5. The KA/AMPA receptor antagonist, GYKI 52466, blocked all KA-induced
      responses regardless of the incubation times.

PMID- 8742500
TI  - The effect of high-dose inhaled budesonide on lipid profile in asthmatic
      patients.
AB  - 1. We determined the effect of high doses of inhaled corticosteroid (budesonide,
      BUD, 1600 micrograms/day for 4 weeks) on fasting triglyceride, cholesterol and
      high-density lipoprotein (HDL)-cholesterol concentration in 11 asthmatic
      patients. 2. No significant change of serum fasting triglyceride concentrations
      was found before and after BUD therapy (p > 0.05). However, serum fasting
      cholesterol concentration decreased slightly (p = 0.03) and HDL-cholesterol
      concentrations increased after BUD therapy for four weeks (p = 0.01). 3. These
      results suggest that high-dose BUD therapy does have minor effects on lipid
      metabolism after long periods of use in asthmatic patients.

PMID- 8742501
TI  - Differential binding of [3H]MK-801 to brain regions and spinal cord of mice
      treated chronically with morphine.
AB  - 1. The effects of morphine tolerance and abstinence on the binding of [3H]MK-801,
      a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptors were
      determined in brain regions and spinal cord of the mouse. 2. Male Swiss-Webster
      mice were rendered tolerant to and physically dependent on morphine by
      subcutaneous implantation of a pellet containing 75 mg of morphine base for 3
      days. Placebo pellet-implanted mice served as controls. In tolerant
      (nonabstinent) mice, the pellets were left intact at the time of sacrificing
      whereas, in the abstinent mice, the pellets were removed 6 hr prior to
      sacrificing. 3. The binding of [3H]MK-801 to membranes prepared from spinal cord
      and brain regions (cortex, pons-medulla, hypothalamus, hippocampus, amygdala,
      striatum, and midbrain) was determined by using a 5 nM concentration of the
      ligand in the presence of 30 microM glycine and 50 microM of glutamate. 4. In
      nonabstinent morphine-tolerant mice, the binding of [3H]MK-801 was decreased in
      pons-medulla and hypothalamus, but was increased in the spinal cord in comparison
      to that in placebo controls. The reduction in binding in pons-medulla was due to
      a decrease in the Bmax value; the Kd value remained unchanged. The binding of
      [3H]MK-801 was increased in the hippocampus of morphine-abstinent mice. 5. These
      studies demonstrate that NMDA receptors of brain regions and spinal cord are
      differentially affected in morphine-tolerant and abstinent mice.

PMID- 8742502
TI  - Effect of exercise and 2-deoxyglucose on the K+ channel opener action of CGRP in
      the guinea pig ureter.
AB  - 1. In the guinea pig isolated ureter, a maximally effective concentration of
      calcitonin gene-related peptide (CGRP, 0.1 microM) produced a prompt and
      transient suppression of myogenic phasic contractions (twitches) evoked by direct
      excitation (electrical field stimulation, EFS) of the smooth muscle. This
      suppressant effect is prevented by glibenclamide (1 and 10 microM), indicating
      the importance of K+ channel activation in its genesis. In the presence of either
      1 or 10 microM glibenclamide, CGRP produced a partial (about 30%) and delayed
      inhibition of the evoked response, but failed to produce a full suppression of
      twitches. 2. The intensity and duration of the early, glibenclamide-sensitive
      suppressant effect of CGRP were inversely related to the frequency at which the
      ureters were driven by EFS. The glibenclamide-resistant inhibitory effect of CGRP
      was unaffected by changes in the EFS driving frequency, and cromakalim (3 microM)
      suppressed twitches independently of the EFS driving frequency. 3. Replacement of
      80% glucose in the Krebs solution with 2-deoxyglucose (2-DOG) reduced the
      amplitude of the EFS-evoked twitches. In the presence of 2-DOG the inhibitory
      effect of CGRP was enhanced and prolonged when tested in the absence, but not in
      the presence, of glibenclamide. 2-DOG counteracted the inhibitory effect produced
      by increasing the EFS driving frequency on the response to CGRP. 4. In sucrose
      gap, both CGRP (0.1 microM) and cromakalim (3 microM) produced prompt
      hyperpolarization of the membrane. During continued superfusion for 15 min in
      unstimulated preparations, the hyperpolarizing effect of cromakalim and CGRP was
      sustained. When tested within 3 min from the end of 'exercise', induced by
      application of EFS at intervals of 15 sec for 30 min, the hyperpolarization by
      CGRP was reduced and shortened but that produced by cromakalim was unaffected. 5.
      These findings demonstrate that exercise and metabolic inhibition selectively
      influence, in opposite directions, the K+ channel opener action of CGRP in the
      guinea pig ureter, indicating that the ability of this neuropeptide to suppress
      latent pacemakers in smooth muscle is markedly dependent upon degree/frequency of
      cell activation. These results suggest that the ability of endogenous CGRP to
      suppress ureteral motility may be inversely related to the frequency of ureteral
      peristalsis, the effect being reduced by, for example, increase in diuresis.

PMID- 8742503
TI  - Positive inotropic and chronotropic effects of beraprost sodium, a stable
      analogue of prostacyclin, in isolated guinea pig myocardium.
AB  - 1. Inotropic and chronotropic effects of beraprost sodium (beraprost), a
      chemically stable prostacyclin analogue, were examined in isolated myocardial
      preparations of guinea pigs. 2. In the left atria, 10(-9) - 10(-7) M beraprost
      had no significant effect on the contractile force, but 10(-6) and 10(-5) M
      produced a concentration-dependent positive inotropic response. This effect was
      antagonized by S-145, a potent and selective thromboxane A2 (TXA2) receptor
      antagonist, but not by propranolol. 3. Beraprost, from 10(-9) to 10(-5) M, had no
      significant inotropic effect in the right ventricular papillary muscles. 4. In
      the right atria, 10(-9) and 10(-8) M beraprost had no significant effect, but 10(
      7) - 10(-5) M caused an increase in beating rate; this effect was not affected by
      S-145. 5. The present study demonstrates that beraprost has positive inotropic
      and chronotropic effects at high doses on isolated guinea pig atria. The
      inotropic effect may be mediated by the TXA2 receptor, but some mechanism other
      than the TXA2 receptor is responsible for the chronotropic effect.

PMID- 8742504
TI  - Capsaicin does not inhibit the intracellular calcium handling process in rat
      ventricular papillary muscle.
AB  - 1. We studied the effects of capsaicin, a pungent agent extracted from red
      pepper, on rested-state contraction (RSC) of isolated rat ventricular papillary
      muscles. 2. The RSC was induced by stimulation, after a rest interval of 5 sec to
      10 min, after the twitch tension of the muscle preparation stimulated at the
      regular stimulus frequency of cycle lengths of 5, 1 or 0.2 sec attained the
      steady state. 3. Drug effects were evaluated on the RSC in the presence of
      capsaicin 10(-5) M, caffeine 10(-2) M or ryanodine 10(-7) M, respectively. 4. All
      drugs inhibited the RSC but to different degrees. Ryanodine was the most
      effective in inhibiting RSC, followed by caffeine and capsaicin, in that order.
      However, the inhibitory mode varied, depending on the drugs. 5. These findings
      suggest that capsaicin may not inhibit the function of intracellular Ca2+ store
      in rat cardiac muscle.

PMID- 8742505
TI  - The effect on ephedrine prodrugs on locomotor activity in rats.
AB  - 1. Five oxazolidines were synthesized by reaction of (-) ephedrine with
      formaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde, and acetone,
      respectively. 2. Half-lives of hydrolysis were measured in pH 7.4 aqueous buffer.
      Half-lives varied from 12 seconds to 11 minutes. 3. The compounds were evaluated
      for their ability to increase locomotor activity in rats. All compounds
      significantly increased locomotor activity at 50 mg/kg dose. 4. The formaldehyde
      derivative had similar activity to (-) ephedrine. All other compounds were less
      active than (-) ephedrine.

PMID- 8742506
TI  - 7-chlorokynurenic acid prevents in vitro epileptiform and neurotoxic effects due
      to kainic acid.
AB  - 1. The effects of 7-chlorokynurenic acid were studied against the epileptiform
      and neurotoxic effects due to the non-NMDA excitatory amino acid, kainic acid, in
      rat hippocampal slices. 2. Slice perfusion with 7-chlorokynurenic acid (100
      microM), significantly (p < 0.05) decreased the duration of the CA1 epileptiform
      bursting due to 1 microM kainic acid. 3. Slice perfusion with 7-chlorokynurenic
      acid (100 microM) significantly (p < 0.05) increased the probability of recovery
      of the CA1 population spike after a neurotoxic concentration (12 microM) of
      kainic acid. 4. The results indicate that 7-chlorokynurenic acid affects, with a
      similar potency, epileptiform and neurotoxic effects due to kainic acid.

PMID- 8742507
TI  - Vasoinhibitory effect of leminoprazole, a H+,K(+)-ATPase inhibitor, on rat aortic
      rings.
AB  - 1. In isolated rat aortic rings, leminoprazole (2-[2-N-methyl-N-(2
      methylpropyl)amino]benzylsulfinyl benzimidazole) (10(-6) - 10(-4) M) inhibited
      contractile responses to phenylephrine (PE), KCl and Ca2+ in KCl-depolarized
      tissues in a Ca2+ free medium. Leminoprazole also relaxed the aorta contracted by
      PE and KCl. 2. The relaxing effect of leminoprazole was markedly inhibited by
      nifedipine and verapamil (inhibitors of voltage operated Ca2+ channels).
      Relaxation induced by verapamil, but not by nifedipine, was inhibited by pre
      treatment by leminoprazole. 3. The relaxing effect of leminoprazole was also
      inhibited by NG-monomethyl-L-arginine (a nitric oxide synthase inhibitor),
      methylene blue (a guanylate cyclase inhibitor) or endothelium removal but not by
      indomethacin (a cyclooxygenase inhibitor), glyburide (a KATP channel inhibitor)
      or iberiotoxin (a KCa channel inhibitor). 4. Zaprinast (a cGMP-phosphodiesterase
      inhibitor) also inhibited the relaxing action of leminoprazole. In addition,
      relaxation induced by nitroglycerin was potentiated by leminoprazole. 5. Further,
      in the presence of methylene blue, residual relaxation induced by leminoprazole
      was still potentiated by verapamil. 6. These results suggest that the
      vasoinhibitory effect of leminoprazole in rat aortic rings is due to the
      increased level of cGMP through inhibition of cGMP-phosphodiesterase and also due
      to inhibition of voltage operated Ca2+ channels.

PMID- 8742508
TI  - Benzalkonium chloride inhibited the histamine release from rat peritoneal mast
      cells induced by bradykinin and GlcNAc oligomer-specific lectin Datura stramonium
      agglutinin, but heparin did not.
AB  - 1. Benzalkonium chloride (BAC) inhibited the histamine release from rat
      peritoneal mast cells induced by synthetic cationic polymers (compound 48/80 and
      PEI6), bradykinin, des-Arg1-bradykinin and des-Arg9-bradykinin and Datura
      stramonium agglutinin (DSA). 2. The anionic polymers heparin, de-N-sulfated
      heparin, poly-aspartic acid and poly-glutamic acid dose dependently inhibited the
      histamine release induced by cationic polymers, suggesting counteraction between
      anions and cations. 3. Inhibition by heparin was diminished but that of BAC
      remained after removal of extracellular heparin and BAC. 4. Mast cell activation
      by bradykinin and DSA was not inhibited by anionic polymers, suggesting that both
      bradykinin and DSA recognize membrane sites as receptors.

PMID- 8742509
TI  - Inhibition of contractile tension by capsaicin in isolated rat papillary muscle.
AB  - 1. We examined effects of capsaicin (10(-9) - 10(-5) M), a pungent agent
      extracted from red pepper, on the contractile tension of rat ventricular
      papillary muscles stimulated at various cycle lengths (0.2, 0.5, 1, 2 and 5 sec).
      2. Capsaicin produced a marked concentration-dependent decrease in the amplitude,
      the rate of rise (dp/dt) and the rate of relaxation (dr/dt) of the tension. 3.
      However, the half relaxation time and the time to peak tension of the tension
      were slightly affected by the agent. 4. The negative inotropic effect of
      capsaicin was stimulus cycle length (CL) dependent. In particular, IC50 (50%
      inhibitive concentration) of the agent in the amplitude of the tension was
      stimulus CL dependent. That is, the values of IC50 were around 10(-7) M at longer
      CLs (1, 2 and 5 sec), and the value of IC50 at CL 0.2 sec was 4 x 10(-6) M. 5.
      These capsaicin-induced negative inotropic effects were reversible. Other studies
      from our laboratory show that the negative inotropic effects may be largely due
      to a decrease in Ca2+ current.

PMID- 8742510
TI  - Inhibition of rats adjuvant arthritis by a bradykinin antagonist Hoe 140 and its
      influence on kallikreins.
AB  - 1. This study examines the effect of Hoe 140, a bradykinin (BK) 2 receptor
      antagonist, indomethacin and prednisolone on chronic adjuvant arthritis of the
      knee in rats. We also evaluated the influence of Hoe 140 on BK-forming enzymes in
      the synovial and paw tissues. 2. Adjuvant arthritis was induced in male Sprague
      Dawley rats in the right knee by injecting 0.05 ml of a fine suspension of heat
      killed Mycobacterium tubercle bacilli in liquid paraffin (5 mg/ml). 3. Hoe 140
      (1.5 mg/kg i.p.), indomethacin (2.5 mg/kg orally) and prednisolone (3.0 mg/kg
      orally) administration for 9 days resulted in significant suppression of knee
      joint swelling. Plasma and tissue kallikrein levels were raised (P < 0.01) in the
      synovial and paw tissues of adjuvant arthritic rats. Hoe 140 treatment reduced (P
      < 0.05) tissue kallikrein but increased (P < 0.01) plasma kallikrein levels in
      synovial tissue. 4. Hoe 140 treatment did not alter (P > 0.05) the raised plasma
      and tissue kallikrein levels in the paw tissue. The findings indicate that Hoe
      140 may be a useful anti-inflammatory agent and BK plays a major role in this
      adjuvant-induced arthritis model.

PMID- 8742511
TI  - Slow association of positively charged Ca2+ channel antagonist amlodipine to
      dihydropyridine receptor sites in rat brain membranes.
AB  - 1. No significant differences were observed in Kd and Bmax values between pH 7.2
      (0.16 +/- 0.01 nM and 155.36 +/- 16.07 fmol/mg protein) and pH 10.0 (0.15 +/-
      0.01 nM and 158.63 +/- 13.80 fmol/mg protein) in rat brain membranes. 2. The IC50
      ratios at 0- and 270-min preincubations of amlodipine and manidipine at pH 7.2
      were 23.09 and 10.25, respectively, whereas these ratios for these two drugs at
      pH 10.0 were 2.63 and 1.34, respectively. 3. In contrast, on treatment with
      nisoldipine, benidipine, SM-6586 and nifedipine, no significant differences were
      observed in the IC50 ratios between 0- and 270-min preincubations at pH 7.2 and
      10.0.

PMID- 8742512
TI  - Sodium nonivamide acetate: a non-pungently antinociceptive capsaicin derivative
      with unusual anti-inflammatory properties.
AB  - 1. Bradykinin-induced vascular pain in conscious rats, hyperalgesia in the rat
      hind paw, rat hind paw edema induced by compound 48/80 and carrageenin and dye
      exudation induced by intraperitoneal injection of 0.7% acetic acid in mice were
      all inhibited by sodium nonivamide acetate (SNA). 2. Collagen and arachidonic
      acid-induced rabbit platelet aggregations were inhibited by SNA and capsaicin. In
      human platelet microsomes, prostaglandin E2 formation in arachidonic acid
      metabolite was not inhibited by SNA but was inhibited by capsaicin and
      indomethacin; thromboxane B2 formation and its synthetase activity were inhibited
      by SNA and capsaicin. 3. In the extracellular recording, SNA could not decrease
      the action potential amplitude of the vagus nerve. 4. The motor activity of mice
      induced by caffeine (1.0 mg/kg) was inhibited by SNA and capsaicin.

PMID- 8742513
TI  - Multiple sensory and functional effects of non-phenolic aminodimethylene
      nonivamide: an approach to capsaicin antagonist.
AB  - 1. Hexylaminodimethylene nonivamide (CAPCNC6, 0.1-10 microM) inhibited the
      contractility of isolated guinea pig right atria, toxically revealed positive
      inotropic, chronotropic and then a cardiac arrest effect at 100 microM and
      inhibited capsaicin (1.0 microM)-induced cardiotonic effects. 2. CAPCNC6 (0.1-10
      microM)-induced aorta contractions were inhibited in the presence of flunarizine,
      atropine, phentolamine, Ca(2+)-free solution and pre-treatment of the animal with
      capsaicin. 3. CAPCNC6 (1.0-300 microM)-induced trachea contractions were
      inhibited in the presence of capsazepine, ruthenium red, hCGRP8-37 and pre
      treatment of the animal with capsaicin.

PMID- 8742514
TI  - The effect of cholecystokinin (CCK-33) and C-terminal fragments of
      cholecystokinin: CCK-8 and CCK-4 on the cardiovascular system in rats.
AB  - 1. The effects of cholecystokinin (CCK-33) and its fragments CCK-8 and CCK-4 on
      arterial blood pressure and the function of isolated rat heart and the amount of
      catecholamines in plasma, heart tissue were studied. 2. The results indicated
      that shortening of CCK to CCK-8 and CCK-4 eliminates the circulatory effect of
      this peptide. 3. A correlation was found between the results of in vivo and in
      vitro experiments and the amount of catecholamines.

PMID- 8742515
TI  - The effect of 2-chloroadenosine on the ATP level Na,K ATPase activity in
      experimental brain ischemia of gerbil.
AB  - T1. The effect of 2-chloroadenosine, an adenosine analogue, on brain ATP level
      and Na,K ATPase activity in ischemia and reperfusion was studied. 2. Na,K ATPase
      activity decreased in both ischemia and reperfusion. Although the ATP level
      decreased in ischemia, it increased with reperfusion (P < 0.05). 3. It is
      concluded that 2-chloroadenosine treatment influenced ATP production and Na,K
      ATPase activity in ischemia and reperfusion (P < 0.05).

PMID- 8742516
TI  - The influence of antagonists of poly(ADP-ribose) metabolism on acetaminophen
      hepatotoxicity.
AB  - An array of therapeutically used analgetic and antirheumatic drugs causes severe
      liver damage. The present study investigates the hepatoprotective effects of
      inhibitors of NAD-dependent adenoribosylation reactions in analgesics-induced
      hepatic injury. Male NMRI mice were treated perorally with 500 mg/kg of
      acetaminophen, and the activities of both glutamate-oxaloacetate transaminase
      (GOT) and glutamate-pyruvate transaminase (GPT) were determined in serum. In
      addition, the activity of poly(ADP-ribose)polymerase (PARP) was quantified in
      liver cell nuclei. While the PARP-activity remained essentially unchanged, the
      acetaminophen-induced release of both GOT and GPT from injured liver cells could
      be inhibited by 90-99%, when mice were injected additionally with the selective
      PARP-inhibitors nicotinic acid amide, benzamide, caffeine, theophyline, and
      thymidine, respectively. We see the main application of inhibitors of
      adenoribosylation reactions as for the combinational use in pharmaceutical
      preparations of analgesics and antirheumatic drugs in order to avoid hepatic
      damage.

PMID- 8742518
TI  - Cefaclor concentration in pus from abscess caused by odontogenic infection after
      a single oral administration.
AB  - 1. Cefaclor concentrations in serum and pus from abscess of odontogenic infection
      after a single oral administration of 500-mg cefaclor were assayed and pus
      concentrations were compared with minimum inhibitory concentration (MIC) of oral
      streptococci isolated from odontogenic infection. 2. The mean peak concentrations
      in serum and pus were found at identical times, 1.5 hr after administration,
      which were 7.22 and 0.72 micrograms/ml, respectively. 3. The mean ratio of
      pus:serum concentration at the peak time was 0.10. 4. Most cefaclor
      concentrations in pus at the peak time (seven of nine cases) exceeded the MIC for
      90% of oral streptococci (0.5 micrograms/ml).

PMID- 8742517
TI  - Mechanisms involved in the spasmolytic effect of extracts from Sabal serrulata
      fruit on smooth muscle.
AB  - 1. The effects of two extracts from Sabal serrulata fruits [total lipidic (L) and
      saponifiable (S)] on smooth muscle contractions have been assayed. 2. Both
      extracts (0.1-1 mg/ml) relaxed the tonic contraction induced by norepinefrine (30
      nM) on rat aorta [EC50, 0.53 +/- 0.05 mg/ml (L) and 0.5 +/- 0.04 mg/ml (S)] and
      by KCl (60 mM) on rat uterus. The Sabal extracts (0.3-1 mg/ml) also antagonized
      the dose-response curve of contractions induced by acetylcholine (0.1-100 microM)
      on urinary bladder. 3. dL-Propranolol (1 microM) but not the inactive (R)-(+)
      propranolol(1 microM) potentiated the Sabal extracts relaxant effect by lowering
      the EC50 (0.35 +/- 0.2 vs 0.20 +/- 0.01 mg/ml for L and 0.43 +/- 0.02 vs 0.19 +/-
      0.02 mg/ml, P < 0.01, for S extract). 4. Cycloheximide (10 micrograms/ml)
      antagonized the effect of extracts from Sabal. However, actinomycin D (5
      micrograms/ml) significantly (P < or = 0.01) antagonized the effect of the total
      lipidic extract without modifying that of the saponifiable extract. 5. The
      relaxant effect of both extracts was not modified by the tyrosine kinase
      inhibitor genistein (10 microM) or the ornithine decarboxylase inhibitor alpha
      difluoromethyl-ornithine (10 mM).

PMID- 8742519
TI  - Role of endothelium in the vasodilating effect of progestins and androgens on the
      rat thoracic aorta.
AB  - 1. In the rat thoracic aorta, contractions induced by noradrenaline were
      inhibited by the steroids progesterone, pregnanolone, testosterone and 5 alpha-
      and 5 beta-dihydrotestosterone. 2. Removal of endothelium did not prevent
      relaxation to the steroids, suggesting that the vasodilating effect of steroids
      occurred on the smooth muscle cells. 3. gamma-Aminobutyric acid (GABA) did not
      modify noradrenaline-induced contraction. Thus, the vasodilation elicited by
      steroids is not apparently mediated by GABA receptors. 4. On the basis that
      noradrenaline opens receptor-operated calcium channels to induce contraction, we
      suggest that relaxation by steroids involves a blockade of this type of channels.

PMID- 8742520
TI  - Effect of volatiles from neem and other natural products on gonotrophic cycle and
      oviposition of Anopheles stephensi and An. culicifacies (Diptera: Culicidae).
AB  - The gonotrophic cycle of female Anopheles was impaired by exposure to volatiles
      of neem, (Azadirachta indica), reetha, (Sapindus mukorossi), and garlic, (Allium
      sativum), but not to castor seeds and cotton seed oil. A brief exposure to
      contact or volatile extracts from neem suppressed rather than inhibited
      oviposition. Complete inhibition of oviposition was observed by exposure of
      mosquitoes to neem oil and 1 fraction containing volatile components.
      Vitellogenesis was impaired irreversably by long-term exposure to neem odor and
      some extracts. The effect of volatiles on oviposition seems to be regulated by
      absorption through the cuticle, although passage through the spiracles could not
      be excluded.

PMID- 8742521
TI  - Polymerase chain reaction used to describe larval habitat use by Anopheles
      gambiae complex (Diptera: Culicidae) in the environs of Ifakara, Tanzania.
AB  - Larvae of the Anopheles gambiae complex were collected in and around the town of
      Ifakara, southern Tanzania during the wet season of 1994 and identified to
      species by polymerase chain reaction. All but 1 surface pool contained mixed
      populations of An. gambiae and An. arabiensis larvae. The 2 species varied among
      locations rather than types of water. An. arabiensis predominated in pools close
      to cattle. The numbers of identified early instars of both species were similar,
      but more An. gambiae 4th instars were identified, perhaps indicating that An.
      gambiae were able to survive heavy rainfall better than A. arabiensis.

PMID- 8742522
TI  - Characterization of Anopheles darlingi (Diptera: Culicidae) larval habitats in
      Belize, Central America.
AB  - Surveys for larvae of Anopheles darlingi Root were conducted in April, May, and
      August 1994 in riverine habitats of central Belize (Cayo and Belize districts).
      An. darlingi was present during both the dry and wet seasons. Larvae were
      encountered most frequently in patches of floating debris along river margins.
      The floating mats were often formed by bamboo hanging over the banks and dense
      submersed bamboo roots. Larvae were found less frequently in lake margins, small
      lagoons, and ground pools with submersed roots and patches of floating leaves or
      vegetation. In addition to their association with floating debris, larvae of An.
      darlingi were associated positively with shade and submersed plants in riverine
      environments. Samples from river habitats showed the larvae of Anopheles
      albimanus Wiedemann to be strongly associated with sun-exposed sites containing
      green or blue-green algae. Unlike An. darlingi, An. albimanus was an ubiquitous
      mosquito, the immatures of which occurred in a wide variety of riverine and
      nonriverine aquatic habitats. Based on published reports and our experience, the
      association of An. darlingi with river systems was verified, and its distribution
      in Central America and Mexico was mapped.

PMID- 8742523
TI  - Developmental synchrony of Ascogregarina taiwanensis (Apicomplexa: Lecudinidae)
      within Aedes albopictus (Diptera: Cuclicidae).
AB  - Development of Ascogregarina taiwanensis Lien & Levine was synchronized with its
      host, the Asian tiger mosquito, Aedes albopictus (Skuse). Trophozoites of the
      parasite migrate to the Malpighian tubules where the gamonts fuse to form
      gametocysts and later mature oocysts. In this study, we observed that water
      temperature, which alters the development time of mosquito larvae, also affected
      parasite development. A. taiwanensis developed in a shorter time at 29 degrees C,
      whereas at 14 degrees C, the development was extended to as long as 17 d. Few
      mature oocysts were produced at 29 degrees C, although gametocysts occasionally
      were found in the lumen of Malpighian tubules. In contrast, gametocysts did not
      develop at 14 degrees C unless pupation occurred. Stage transformation of the
      parasite was determined by the metamorphosis of the mosquito host. Gametocyst
      formation occurred earlier when infected larvae were injected with an appropriate
      concentration of 20-hydroxyecdysone, indicating this molting hormone was involved
      in regulating the synchronous development of A. taiwanensis in its mosquito host.

PMID- 8742524
TI  - Isolation and characterization of mouse monoclonal antibodies reactive with soft
      tick (Acari: Argasidae) salivary antigens of high molecular weight.
AB  - The purpose of this study was to immunologically characterize soft tick salivary
      antigens. BALB/c mice hyperimmunized with salivary gland extract prepared from
      Ornithodoros talaje (Guerin-Meneville) were observed to develop high titers of
      antitick salivary antigen antibodies. Subsequent fusion of splenic lymphocytes
      from the hyperimmunized mice with SP-2/0-AG14 myeloma cells resulted in the
      production of 10 antitick IgM-producing hybridoma clones. Partial
      characterization of the respective tick antigens by gel filtration and SDS-PAGE
      demonstrated all 10 monoclonal antitick antibodies to be reactive with a salivary
      gland extract fraction containing proteins 50-110 kDa in molecular weight. Cross
      reactivity assays and electrophoretic comparison of salivary gland extract
      specimens demonstrated similar proteins in several ixodid tick genera and
      species.

PMID- 8742525
TI  - Warble stage development of third instars of Hypoderma lineatum (Diptera:
      Oestridae).
AB  - Hypoderma lineatum (Villers), the common cattle grub, is an insect parasite that
      resides in a warble in the subcutaneous tissues of the backs of cattle during a
      portion of their life cycle. Inside the warble, the larva undergoes 2 molts to
      the 3rd instar. In this study, the development of the posterior spiracular plates
      of the 3rd instar of H. lineatum was observed in situ. Larvae were observed to
      molt to the 3rd-instar phase 1 stage of development 28.6 +/- 3.9 d (+/- SD) after
      digesting a breathing hole in the backs of previously uninfested calves.
      Development of the spiracular plates through each of the various recognizable
      stages occurred on a 5-6-d interval. It took 54.2 +/- 5.1 d in the back for
      larvae to develop to the phase 3 stage, the stage reached before larvae exit the
      host. The average elapsed time from the 3rd-instar phase 3 stage to exit from the
      host was 5.5 +/- 2.9 d. Of 22 larvae that were followed from arrival in the back
      to pupariation, the elapsed time was 59.4 +/- 6.1 d. Most larval mortality
      occurred in the back during the 1st and 2nd instar. Of larvae surviving to the
      3rd instar, 86.7% successfully exited from the host. Of 3rd instars surviving to
      the phase 2 goldplate or phase 3 stage, 93.3% exited successfully from the host.

PMID- 8742526
TI  - Ticks (Acari: Ixodidae) in Bulloch County, Georgia.
AB  - An 18-mo study was conducted in Bulloch County, Georgia, to determine tick
      species composition, seasonal activity of individual tick species, and host-tick
      associations. The following 7 methods of tick collection were included: (1) live
      trapping of potential host animals, (2) checking wild game, (3) drag sampling,
      (4) carbon dioxide attraction, (5) checking livestock, road kills, nests, and
      burrows, (6) samples submitted from veterinarians, and (7) ticks collected by
      local residents and submitted for identification. Twelve tick species (Ixodidae)
      were identified. Blacklegged tick, Ixodes scapularis Say, and American dog tick,
      Dermacentor variabilis (Say), had the widest host ranges and were the most
      numerous. White-tailed deer, Odocoileus virginianus (Zimmermann), supported 5
      tick species, the greatest number on any host. Of 55 animal species examined, 16
      mammal, 5 bird, and 3 reptile species were parasitized by ticks. Opossums,
      Didelphis virginiana Kerr, and cotton mice, Peromyscus gossypinus (LeConte), were
      the most commonly examined wild animals.

PMID- 8742527
TI  - Laboratory tests of arthropod repellents against Leptotrombidium deliense-
      noninfected and infected with Rickettsia tsutsugamushi--and noninfected L.
      fletcheri (Acari: Trombiculidae).
AB  - Laboratory tests were conducted to compare the response of noninfected
      Leptotrombidium deliense Sambon and Leptotrombidium fletcheri (Womersley &
      Heaslip) and L. deliense naturally infected with Rickettsia tsutsugamushi, the
      etiologic agent of scrub typhus, to 8 chemical repellents and toxicants. Low
      concentrations of permethrin, dimethylphthalate, diethyl methylbenzamide, benzyl
      benzoate, di-n-propyl 2,5-pyridine-dicarboxylate, 1-(3-Cyclohexen-1-yl-carbonyl)
      2-methylpiperidine (AI3-37220), 2-hydroxymethyl-cyclohexyl acetic acid lactone,
      and a high concentration of dibutylphthalate (DBP) were toxic for noninfected
      larvae of both species tested. The median effective knockdown time for all
      chemicals, except 1% AI3-37220 and 5% permethrin, were longer against infected L.
      deliense than uninfected larvae of the same species. However, the results
      indicate that low concentrations of all chemicals, except DBP, should be
      effective against 2 important vectors of scrub typhus.

PMID- 8742528
TI  - Responses of Sarcoptes scabiei (Acari: Sarcoptidae) to nitrogenous waste and
      phenolic compounds.
AB  - This study found that > or = 1 life stage(s) of Sarcoptes scabiei (L.) was
      significantly attracted to the nitrogenous compounds, guanine, purine, adenine,
      allantoin, hypoxanthine, xanthine, uric acid, ammonium chloride, ammonium
      nitrate, and ammonium sulfate. Females and larvae responded to all compounds.
      Males responded to all compounds except purine and allantoin. Nymphs responded to
      all compounds except allantoin. Some specific concentrations of compounds
      attracted only 1 life stage but other concentrations attracted multiple life
      stages. Also, some life stages were attracted by multiple concentrations of a
      compound. The concentration that induced the greatest response by a particular
      life stage varied between life stages. Overall, greater percentages of females
      were attracted to the nitrogenous compounds than any other life stage. Females
      responded to more concentrations of a compound compared to other life stages.
      Males responded to fewer concentrations then immatures. In addition, all life
      stages of S. scabiei were significantly attracted to the phenolic compounds, 2,6
      dichlorophenol, methyl salicylate, and 2-nitrophenol. Nymphs followed by females
      responded to the most concentrations. The results indicated that these
      nitrogenous wastes and phenolic compounds acted in a pheromone-like manner that
      induced assembly of these ectoparasitic mites.

PMID- 8742529
TI  - Hypopi (Acari: Hypoderatidae) from the roseate spoonbill (Aves: Ciconiiformes;
      Threskiornithidae).
AB  - A new species and additional host records for 4 other species of quiescent
      deutonymphs (hypopi) of mites of the family Hypoderatidae are described from the
      subcutaneous adipose tissues of a roseate spoonbill, Ajaia ajaja L., in Florida.
      The hypopus of Phalacrodectes parvus n. sp. most closely resembles that of P.
      platalea Pence & Duncan from the African spoonbill, Platalea alba Scopali, in
      idiosomatic chaetotaxy and structure of the genital apparatus. It differs from
      this and other species of the genus in the shape of the idiosoma, pattern and
      density of idiosomatic sclerotization, the unique posterior extension of
      secondary sclerotization from the perigenital area, large size and more posterior
      location of genital seta gm, and small size and sharp-tipped spinelike structure
      of seta hT on tibia II. In addition to the new species, this roseate spoonbill
      also was infected with P. whartoni Fain and 3 other less common species of
      hypoderatid deutonymphs. A key to the deutonymphs of species in the genus
      Phalacrodectes is presented.

PMID- 8742530
TI  - On-host viability and fecundity of Ctenocephalides felis (Siphonaptera:
      Pulicidae), using a novel chambered flea technique.
AB  - The on-host viability and fecundity of cat fleas, Ctenocephalides felis (Bouche),
      confined within a novel chambering system are described. Using this system, all
      fleas and flea eggs are recovered from chambers after fleas have fed on cats.
      Thus, accurate calculations of both adult flea survival and female flea fecundity
      can be made. The technique provides a microenvironment in which adult fleas
      exhibit > 90% survival over 14 d. Female fleas lay an average of 9.5 eggs per day
      on the 2nd d of feeding, 22.1 eggs per day between days 3 and 7, and 19.6 eggs
      per day between days 3 and 14. These numbers are similar to values previously
      reported for studies in which fleas were not confined. The technique permits
      accurate, multiple sampling of experimental flea populations during a study, and
      does not require the use of pesticides or extensive combing to collect surviving
      fleas at the end of a study. Moreover, the technique does not require that cats
      be caged or prevented from grooming. Collecting data from fleas confined in
      chambers is much less time consuming and labor intensive than studies with free
      roaming fleas.

PMID- 8742531
TI  - Development and fecundity of Dermatophagoides farinae (Acari: Pyroglyphidae).
AB  - Duration of the life cycle at 16, 23, 30, and 35 degrees C and fecundity at 23
      degrees C and 75% RH were determined for the American house dust mite,
      Dermatophagoides farinae Hughes. Lengths of the life cycles at 23 and 30 degrees
      C were 35.6 +/- 4.4 and 17.5 +/- 1.2 d, respectively. Few eggs completed
      development to the adult stage at 16 and 35 degrees C. At 23 degrees C and 75%
      RH, the preoviposition period was 3.7 +/- 1.1 d following emergence of the female
      from the tritonymph. The average reproductive period was 34.0 +/- 10.7 d with a
      mean total of 65.5 +/- 17.4 eggs produced per female. Female longevity after
      cessation of egg production was 63.3 +/- 64.6 d.

PMID- 8742532
TI  - Variability in the relationship between weight and wing length of Anopheles
      gambiae (Diptera: Culicidae).
AB  - The relationship between wing length and body weight of female Anopheles gambiae
      Giles reared at 3 densities and at 3 temperatures was examined. Although overall,
      weight was proportional to wing length raised to the 4th power, the relationship
      within treatments was linear. The slope of the regression line varied
      significantly among treatments. Therefore, wing length of mosquitoes caught from
      field populations may not be an adequate measure of body weight if the conditions
      under which the mosquitoes have developed are not known.

PMID- 8742533
TI  - Differentiation of females in Sergentomyia sensu stricto (Diptera: Psychodidae)
      using scanning electron microscopy of pharyngeal armatures.
AB  - Scanning electron microscopy of external ornamentation and internal armature of
      the pharynx was used to identify females of Sergentomyia sensu stricto. Five
      species from the eastern Mediterranean basin were compared; S. minuta clearly was
      separated from species of the fallax-group. Within the fallax-group, S. fallax
      was distinguished readily by its heart-shaped pharynx and the difference in
      armature between the dorsal and lateral plates.

PMID- 8742534
TI  - Water wells as a habitat of sand fly (Diptera: Psychodidae) vectors of visceral
      leishmaniasis in Greece.
AB  - Overall, 37 of 79 water wells in 3 diverse geographic areas of Greece were found
      to harbor sand flies. The predominant species were Phlebotomus tobbi Adler,
      Theodor & Lourie and P. neglectus Tonnoir, species implicated in the transmission
      of Leishmania infantum Nicolle. Three additional species of Phlebotomus and 2
      Sergentomyia spp. also encountered. Wells appear to be resting and possibly
      breeding habitat for sand flies in Greece.

PMID- 8742535
TI  - Reengineering consultation-liaison psychiatry.

PMID- 8742536
TI  - An agenda for primary care psychiatry.
AB  - With the advent of managed care and the primary care gatekeeper, psychiatry's
      relationship to primary care is shifting. Four recent surveys suggest that, in
      general, departments of psychiatry have done little to restructure their
      relationships with primary care. This article proposes an agenda for developing
      primary care psychiatry programs in departments of psychiatry. The rationale for
      shifting resources toward primary care psychiatry is followed by a discussion of
      the goals of primary care psychiatry programs. The agenda presents specific high
      priority projects in the areas of research, education, and clinical care, citing
      examples of existing initiatives and discussing the resources needed for funding
      primary care psychiatry programs.

PMID- 8742537
TI  - Relationship of psychiatric morbidity and psychosocial factors in organ
      transplant candidates.
AB  - The purpose of this study was to explicate the statistical relationship between
      psychiatric diagnosis and psychosocial adjustment and health status in organ
      transplant candidates. Interview and psychometric data were obtained from 311
      heart, kidney, lung, and liver transplant candidates. Over 60% of the cases met
      criteria for DSM-III-R Axis I diagnoses, nearly 32% for Axis II disorders. Axis
      II disorders were significantly associated with medical compliance problems,
      whereas Axis I disorders were predominantly associated with poorer psychosocial
      adjustment and health status. Nearly one-quarter of the patients had comorbid
      Axis I and Axis II disorders, and evidenced poorest premorbid coping and degree
      of marital harmony, defining a subgroup at special risk for problematic outcome.
      The incidence of psychiatric disorders and their association with lack of
      psychosocial resources and poor physical health supports the use of systematic,
      multidisciplinary assessment of transplant candidates.

PMID- 8742538
TI  - Prevalence of anxiety disorders in a clinic-based sample of pediatric asthma
      patients.
AB  - Psychosocial variables may affect the clinical course of childhood asthma. In
      this study, 37 children with asthma were assessed for DSM-III-R anxiety disorders
      with the Schedule for Affective Disorders and Schizophrenia for School-Age
      Children and intrafamilial stress with the Index of Family Relations. When
      compared with a healthy control group, the asthma group had significantly more
      total anxiety disorders, past school problems, past psychiatric illnesses, and
      intrafamilial stress. There was also more family history of emotional problems in
      the asthma group. The implications of these findings for clinical management of
      this population are discussed.

PMID- 8742539
TI  - Posttraumatic stress disorder in mothers of pediatric cancer survivors.
AB  - Prevalence of posttraumatic stress disorder (PTSD) in 24 mothers of pediatric
      cancer survivors was compared with its prevalence among 23 mothers of healthy
      children. Significantly more mothers of pediatric cancer survivors were diagnosed
      with lifetime PTSD. Significant differences were also found in lifetime arousal,
      as well as current and lifetime reexperience and avoidance symptom clusters.
      Significant difference existed in the distribution of the number of prediagnosis
      high-magnitude events experienced by the mothers diagnosed with current PTSD as
      compared with the prediagnosis experience of the mothers who were not diagnosed
      with current PTSD. Illness severity, level of perceived family and extrafamilial
      social support, and Symptom Checklist-90-Revised global severity index scores did
      not significantly differ in the PTSD-positive and PTSD-negative groups.

PMID- 8742540
TI  - Psychological factors affecting self-excoriative behavior in women with mild-to
      moderate facial acne vulgaris.
AB  - The authors examined the psychological factors associated with self-excoriative
      behavior among 56 women (mean +/- SE age: 24.0 +/- 1.0 years) with mild-to
      moderate facial acne vulgaris. Ratings associated with poor self-concept, such as
      perfectionistic and compulsive personality traits, correlated more strongly with
      self-excoriative behavior than the dermatologic indices of acne severity. The
      study's findings suggest that psychological factors, independent of acne
      severity, play an important role in the perpetuation of the self-excoriative
      behavior exhibited by some women with acne.

PMID- 8742541
TI  - Death rates in 71 men with antisocial personality disorder. A comparison with
      general population mortality.
AB  - Mortality data are presented from a 16- to 45-year follow-up study of 71 men with
      antisocial personality disorder. Death ascertainment was made through both a
      personal follow-up and use of the National Death Index. Comparisons were made
      with the mortality experience of the general population of the state of Iowa by
      using gender and age standardized mortality ratios. Seventeen men died (24%) died
      during the follow-up. Antisocial men younger than 40 years were at excessive risk
      for premature death (standardized mortality ratio [SMR] = 33, P < 0.25): men
      between ages 40 and 60 years also appeared to be at risk for premature death,
      although the excess was not statistically significant. Three subjects (18% of all
      deaths) died of complications from diabetes mellitus (SMR = 14, P < 0.05). Deaths
      were spread out among the four decades of follow-up. The findings and their
      implications are discussed.

PMID- 8742542
TI  - Identification of PTSD in cancer survivors.
AB  - The authors measured the rate and determinants of posttraumatic stress disorder
      (PTSD) in a group of cancer survivors. Patients who had a history of cancer
      diagnosis with at least 3 years since diagnosis, receiving no active treatment,
      such as chemotherapy or radiation, were interviewed (N = 27). Patients, who were
      part of the DSM-IV PTSD field trial, were compared with a community-based control
      group matched for age and socioeconomic status. One member of the survivor group
      (4%) and no members of the control group met criteria for current PTSD (NS). Six
      of the survivors (22%) and no control subjects met lifetime criteria (P < 0.02).
      Cancer patients have a higher rate of PTSD than found in the community. Symptoms
      closely resemble those of individuals who have experienced other traumatic
      events.

PMID- 8742544
TI  - Psychiatric disorder and outcome in irritable bowel syndrome.
AB  - A link between irritable bowel syndrome (IBS) and psychiatric illness is well
      recognized. The authors set out to establish whether a group with a risk of poor
      outcome IBS could be identified at presentation to a general hospital clinic in a
      prospective series of 70 subjects. Potential risk factors showed no correlation
      with IBS outcome at 6-9 months. There was a high rate of persistent mental
      illness. Clinicians offering specialist care for IBS should consult with
      psychiatric services to provide assessment irrespective of IBS outcome if major
      psychopathology is not to be neglected.

PMID- 8742543
TI  - Bone marrow transplantation vs. high-dose cytorabine-based consolidation
      chemotherapy for acute myelogenous leukemia. A long-term follow-up study of
      quality-of-life measures of survivors.
AB  - Thirty patients previously treated for acute leukemia were studied on the average
      of 5-6.5 years postdiagnosis in regard to issues of quality of life. Of these 30,
      11 were treated with bone marrow transplantation, 19 were treated with
      conventional chemotherapy. Overall, significant differences were not found
      between the two groups in regard to evidence of depression symptoms, multifocal
      psychiatric symptomatology, or on any subscale of a test evaluating problems and
      rehabilitation needs of cancer patients. A step-wise regression was done,
      controlling for baseline covariates that included type of medical treatment,
      months since diagnosis, type of induction chemotherapy protocol, sex of patient,
      and age of patient. Significant differences in quality of life were not found
      between the treatment groups.

PMID- 8742545
TI  - Cerebral mucormycosis presenting a psychiatric distress.

PMID- 8742546
TI  - Serotonin reuptake inhibitor-related extrapyramidal side effects in two patients
      with cerebral palsy.

PMID- 8742547
TI  - Schizophrenia vs. neurosarcoidosis in a young male.

PMID- 8742548
TI  - Scientific Methods for Prevention Intervention Research. Proceedings of a
      meeting. 1992.

PMID- 8742549
TI  - Prevention intervention research: focus and perspective.

PMID- 8742550
TI  - Testing theory through developmental epidemiologically based prevention research.

PMID- 8742551
TI  - Hypothesis formulation and testing in substance use prevention research.

PMID- 8742552
TI  - Target populations and interventions in prevention research: what is high risk?

PMID- 8742553
TI  - Some design, measurement, and analysis pitfalls in drug abuse prevention research
      and how to avoid them: let your model be your guide.

PMID- 8742554
TI  - Correction for the design effect in school-based substance use and abuse
      prevention research: sample size requirements and analysis considerations.

PMID- 8742555
TI  - Analysis of mediating variables in prevention and intervention research.
AB  - Mediational analysis is one way to test specific hypotheses derived from theory.
      Although this analysis has been suggested in the prevention literature, mediation
      analysis rarely is conducted. As the field of prevention matures, more questions
      about how prevention programs work (or fail to work) will emerge. Studies of
      mediation can address these questions, thereby reducing the cost and enhancing
      the impact of prevention programs. The methods outlined here can be applied in
      the evaluation of primary, secondary, and tertiary prevention programs. Since
      most prevention studies include measurement of some mediating constructs,
      mediation effects can be assessed on many existing data sets. Mediation analysis
      can be used to test ideas about prevention.

PMID- 8742556
TI  - Summary of critiques from the drug abuse epidemiology and prevention research
      review committee.

PMID- 8742557
TI  - Issues in drug abuse prevention intervention research with African Americans.

PMID- 8742558
TI  - Drug prevention research with Hispanic populations: theoretical and
      methodological issues and a generic structural model.

PMID- 8742559
TI  - Drug prevention research with Native-American populations: some considerations.

PMID- 8742560
TI  - Drug abuse prevention research concerns in Asian and Pacific Islander
      populations.

PMID- 8742561
TI  - Influence of intensive diabetes treatment on quality-of-life outcomes in the
      diabetes control and complications trial.
AB  - OBJECTIVE: To evaluate the effect of intensive diabetes treatment on patient
      quality of life assessed by the Diabetes Quality-of-Life Measure, the Symptom
      Checklist-90R, the Medical Outcome Study 36-Item Short Form Survey, and
      intercurrent psychosocial events in the Diabetes Control and Complications Trial
      (DCCT). RESEARCH DESIGN AND METHODS: The DCCT was a 29-center prospective
      controlled clinical trial that demonstrated the beneficial effect of intensive
      diabetes treatment on retinopathy, nephropathy, and neuropathy. The 1,441
      volunteers with IDDM, aged 13-39 years, were randomly assigned to intensive or
      conventional diabetes therapy. The volunteers were followed for a mean of 6.5
      years (range 3-9 years). Quality-of-life data were collected during annual
      visits. Of the volunteers, 99% completed the study, and > 95% of scheduled tests
      were completed. RESULTS: All analyses of quality of life, psychiatric symptom
      indexes, and psychosocial event data showed no differences between intensive and
      conventional diabetes treatment. CONCLUSION: Under careful treatment conditions,
      such as those followed in the DCCT, patients undergoing intensive diabetes
      treatment do not face deterioration in the quality of their lives, even while the
      rigor of their diabetes care is increased.

PMID- 8742562
TI  - Symptoms and well-being in relation to glycemic control in type II diabetes.
AB  - OBJECTIVE: To describe the cross-sectional relation between glycemic control and
      physical symptoms, emotional well-being, and general well-being in patients with
      type II diabetes. RESEARCH DESIGN AND METHODS: The study population consisted of
      188 patients with type II diabetes between 40 and 75 years of age. Patients were
      treated with blood glucose-lowering agents or had either a fasting venous plasma
      glucose level > or = 7.8 mmol/l or an HbA1c level > 6.1%. Multiple regression
      analyses were performed. Dependent variables were scores on the Type II Diabetes
      Symptom Checklist, the Profile of Mood States, the Affect Balance Scale, and
      questions regarding general well-being. The primary determinant under study was
      HbA1c. In addition, age, sex, neuroticism (indicating a general tendency to
      complain), insulin use, and comorbidity were included as determinants in all
      analyses. Other potential determinants taken into consideration were hypoglycemic
      complaints, marital status, diabetes duration, cardiovascular history, blood
      pressure, BMI, waist-to-hip ratio, perceived burden of treatment, and smoking.
      None of these potential determinants had to be included to correct confounding of
      the relation between HbA1c and well-being scores. RESULTS: Higher HbA1c levels
      were significantly associated with higher symptom scores (total score,
      hyperglycemic score, and neuropathic score), with worse mood (total score,
      displeasure score, depression, tension, fatigue), and with worse general well
      being. The relative risks varied between 1.02 and 1.36 for each percentage
      difference in HbA1c. The relation between HbA1c and some mood states was modified
      by neuroticism: in the less neurotic patient (i.e., one who is less inclined to
      complain), the relation was more evident. CONCLUSIONS: These data suggest that
      better glycemic control in type II diabetes is associated with fewer physical
      symptoms, better mood, and better well-being, in a nonhypoglycemic HbA1c range.

PMID- 8742563
TI  - Attending the diabetes center is associated with increased 5-year survival
      probability of diabetic patients: the Verona Diabetes Study.
AB  - OBJECTIVE: The aim of the present study is to compare the survival of patients
      attending diabetes centers with that of patients exclusively consulting family
      physicians. RESEARCH DESIGN AND METHODS: The study was carried out in the frame
      of the Verona Diabetes Study, a population-based survey of known diabetes
      prevalence with a subsequent 5-year mortality follow-up. A cohort of 7,488
      diabetic patients were identified on 31 December 1986 from three different
      sources: a drug consumption database, family physicians, and diabetes centers
      (one for children and one for adults). As of 31 December 1986, 3,288 patients in
      the entire cohort exclusively consulted their own family physicians, while 4,200
      patients also had periodic examinations at the diabetes centers. The life status
      of the diabetic cohort was ascertained on 31 December 1991. RESULTS: Compared
      with the nondiabetic population, diabetic patients seen only by family physicians
      had a standardized mortality ratio (SMR) of 1.62 (95% CI 1.51-1.74), while
      patients attending both family physicians and diabetes centers showed an SMR of
      1.44 (1.34-1.54), the difference being statistically significant (P = 0.017). The
      5-year survival probability, estimated by the Kaplan-Meier method, was 0.76 (0.75
      0.78) in patients seen only by family physicians and 0.81 (0.80-0.82) in patients
      attending the diabetes centers. Multivariate analysis by Cox regression model
      showed that attending the diabetes centers was an independent predictor of
      survival even after adjusting for sex, age, and therapy of diabetes. The relative
      risk of 5-year all-cause mortality amounted to 0.83 (0.75-0.92) in patients also
      attending the diabetes centers with respect to patients consulting only family
      physicians (P < 0.001). CONCLUSIONS: These data on patients' survival indicate
      that diabetes centers play a crucial role in diabetes care. As a corollary, an
      integration between primary-care physicians and diabetes centers is strongly
      recommended.

PMID- 8742564
TI  - Is the incidence of diabetes increasing in all age-groups in The Netherlands?
      Results of the second study in the Dutch Sentinel Practice Network.
AB  - OBJECTIVE: To assess possible changes in the incidence of diabetes in all age
      groups in The Netherlands during a 10-year period (1980-1983/1990-1992). RESEARCH
      DESIGN AND METHODS: Since 1970, a network of sentinel stations (the Dutch
      Sentinel Practice Network) consisting of approximately 1% of the Dutch population
      has been in operation to gain insight into the morbidity patterns of the Dutch
      population as recorded by general practitioners. One of the items recorded from
      1990 to 1992 was the incidence of diabetes. The first study with a similar design
      that registered the incidence of diabetes was conducted from 1980 to 1983.
      RESULTS: The overall incidence of diabetes increased significantly by 12.1% in
      the period between the two studies. This overall increase can largely be
      attributed to a statistically significant increase in the age-group 45-64 years
      (30.5%). Although not statistically significant, the 36% increase of diabetes in
      the age-group 0-19 years is in accordance with the increase of type I diabetes
      based on the first and second nationwide retrospective studies covering the total
      Dutch population. CONCLUSIONS: There is a marked increase in the incidence of
      diabetes in the age-group 45-64 years. This selective increase is probably not
      due to a real rise caused by changes in exposure to risk factors but to an
      earlier recognition of symptoms and signs of diabetes followed by blood glucose
      measurements and/or to more intensive case finding in general practice.

PMID- 8742565
TI  - A comparison of renal disease across two continents; the epidemiology of diabetes
      complications study and the EURODIAB IDDM Complications Study.
AB  - OBJECTIVE: To compare prevalence rates of increased albumin excretion in the
      Epidemiology of Diabetes Complications Study (EDC) (in the U.S.) to similar rates
      in the EURODIAB study (in Europe) and determine if any differences relate to
      hypertension, glycemic control, or smoking status. RESEARCH DESIGN AND METHODS:
      The study population is made up of two epidemiological clinic-based IDDM
      populations with comparable ages (chi = 28 years, both studies), sex distribution
      (50% male, EURODIAB; 49% male, EDC), and duration characteristics. Comparison of
      two cross-sectional (prevalence) studies was made. Despite different laboratory
      assays, comparability was established for urinary albumin (r = 0.98) and GHb
      measures (r = 0.95). Hypertension was measured with an identical protocol. Renal
      status was determined by 24-h urine albumin excretion (< 20 micrograms/min
      normal, 20-200 micrograms/min microalbuminuria, > 200 micrograms/min
      macroalbuminuria) in EURODIAB. Identical cutoffs were used for EDC, though two of
      three samples (24-h, 4-h clinic, and/or overnight sample) had to be positive in
      one range. (Main findings are confirmed using only 24-h results from EDC.)
      RESULTS: The prevalence of macroalbuminuria was higher in EDC (27%) than in
      EURODIAB (12%). Rates of microalbuminuria were similar (22 vs. 25%,
      respectively). These patterns were seen at all durations and ages and in both
      sexes. Controlling for glycemic control, hypertension, or smoking did not account
      for the higher rate in EDC, nor did exclusion of subjects with raised serum
      creatinine. CONCLUSIONS: Advanced renal disease is more prevalent in IDDM in EDC
      (Pittsburgh, PA) than in Europe. This is not explained by hypertension, glycemic
      control, or smoking.

PMID- 8742566
TI  - Circulating catecholamines and metabolic effects of captopril in NIDDM patients.
AB  - OBJECTIVE: To evaluate the effects of captopril on circulating catecholamine
      levels in NIDDM patients and the possible relationship between captopril-related
      changes in circulating catecholamine levels and insulin sensitivity. RESEARCH
      DESIGN AND METHODS: Fourteen nonobese normotensive NIDDM men (aged 44.5 +/- 5.1
      years) underwent a 2-h euglycemic-hyperinsulinemic clamp (40 mU.m-2.min-1).
      Baseline evaluation of insulin sensitivity was followed by the random assignment
      of each patient to either captopril or placebo treatment, according to a
      crossover double-blind design. Euglycemic-hyperinsulinemic clamp studies were
      then repeated for all patients after both placebo and captopril treatments.
      Plasma norepinephrine (NE) and epinephrine (E) levels were assessed before,
      during, and after each clamp. RESULTS: Resulting data showed that plasma
      catecholamine levels increased during baseline euglycemic-hyperinsulinemic clamp
      (NE: +23.6% time 0 vs. time 120 min, P < 0.05; E: +24.8% time 0 vs. time 120 min,
      P < 0.05). Captopril treatment significantly increased total glucose uptake (from
      19.0 +/- 9.0 to 26.8 +/- 10.1 mmol.kg-1.min-1, P < 0.05) and reduced baseline
      plasma NE (P < 0.001) and E (P < 0.05) levels. However, the magnitude of the NE
      (+25.7% time 0 vs. time 120 min, P < 0.001) and E (+27.2% time 0 vs. time 120
      min, P < 0.05) increments during euglycemic hyperinsulinemia were not affected by
      the drug. Percentage changes in the ratio of total body glucose uptake to
      circulating insulin levels and corresponding decrements of baseline plasma E
      levels after captopril therapy were negatively correlated (r = -0.57, P < 0.05).
      CONCLUSIONS: The reduction of circulating catecholamines could contribute, at
      least in part, to the captopril-related amelioration of insulin sensitivity.

PMID- 8742567
TI  - No difference in cardiac innervation of diabetic patients with painful and
      asymptomatic coronary artery disease.
AB  - OBJECTIVE: To test the hypothesis that diabetic autonomic neuropathy interfering
      with sensory impulses from the heart by sympathetic denervation is the major
      cause of the high prevalence of asymptomatic coronary artery disease (CAD) in
      diabetic patients. RESEARCH DESIGN AND METHODS: We evaluated cardiac sympathetic
      innervation in a population-based group of 10 asymptomatic diabetic patients with
      angiographically proven CAD and in an age- and sex-matched group of 10 diabetic
      patients with symptomatic CAD using [123I]metaiodobenzylguanide (MIBG)
      scintigraphy. Exercise electrocardiography and myocardial perfusion imaging by
      201Tl were used to detect myocardial ischemia, and standard cardiovascular tests
      were used to diagnose autonomic nervous dysfunction. RESULTS: Thallium
      scintigraphy revealed perfusion defects in all 10 symptomatic patients and in 9
      of the asymptomatic patients. MIBG accumulation defects were found in all cases
      with painless and with painful disease. In the asymptomatic group, the
      denervation area exceeded the ischemic area in six cases and areas with total
      MIBG accumulation defects were seen in four cases. In one case, the MIBG defect
      was not in the ischemic region. In the symptomatic group, the denervation area
      exceeded the area of the ischemic region in all cases and areas of total
      denervation were seen in six cases. The autonomic nervous function tests were
      abnormal in two asymptomatic and three symptomatic patients with CAD.
      CONCLUSIONS: Cardiac sympathetic denervation is common in both patients with
      painful CAD and patients with asymptomatic CAD regardless of diabetic autonomic
      neuropathy. This finding supports the view that sympathetic innervation of the
      heart is highly sensitive to ischemia and this profound effect of ischemia masks
      the potential effects of autonomic neuropathy on sympathetic innervation.
      Mechanisms leading to the lack of ischemic pain in diabetic patients with CAD are
      complex and are not solely explained by autonomic neuropathy.

PMID- 8742568
TI  - Continued insulin dependence despite normal range insulin sensitivity and insulin
      connecting peptide levels in a kidney/islet transplant patient.
AB  - OBJECTIVE: The majority of islet transplant recipients remain insulin-requiring,
      although many have near-normal connecting peptide (CP) levels. Insulin resistance
      may be one possible cause of the continuing need for exogenous insulin in islet
      transplant recipients. To assess this, we have studied the insulin sensitivity
      index (S1) in one patient with near-normal CP levels after islet transplant who
      remained insulin-requiring. RESEARCH DESIGN AND METHODS: The islet transplant
      recipient is a 36-year-old woman with no residual CP who received a kidney
      transplant, followed 7 days later by an islet transplant. The islets were infused
      into the liver via the umbilical vein. Induction immunosuppression consisted of
      OKT3, prednisone, cyclosporin A, and azathioprine, with maintenance on the latter
      three. RESULTS: Maximum CP levels after a standardized Sustacal meal were 2.09,
      1.18, 0.85, and 0.81 nmol/l at 1,6,18, and 24 months posttransplant,
      respectively. Insulin requirements at the same times were 0.27, 0.45, 0.49, and
      0.62 U.kg(-1).d(-1), while S1 was 36.3, 53.3, and 13.2 min (-1).nmol(-1).ml at
      6,18, and 24 months, respectively. This compares with S1 values of 43.3+/- 10.0
      min (-1).nmol(-1).ml for normal subjects. CONCLUSIONS: This patient had near
      normal S1 and CP levels, but she was unable to discontinue insulin therapy,
      suggesting that other factors are critical. Despite this, she maintained normal
      or near-normal glycated hemoglobins, indicating metabolic benefit from the islet
      transplant.

PMID- 8742570
TI  - Diminished thyroxine-binding globulin in pubertal diabetic children.
AB  - OBJECTIVE: To determine the effect of diabetes on thyroid hormone and thyroxine
      binding globulin (TBG) concentrations during puberty. RESEARCH DESIGN AND
      METHODS: Total thyroxine (TT4), free thyroxine (FT4), and TBG levels of 171
      thyroid microsomal antibody-negative subjects with normal thyroid-stimulating
      hormone (TSH) levels were measured and compared with those of nondiabetic
      adolescents. A random subset of 68 diabetic patients (40 boys and 28 girls) and
      51 control subjects (24 boys and 27 girls) were analyzed for puberty-related
      changes. RESULTS: Most TT4 levels of diabetic subjects (80% of girls and 63% of
      boys) were below the 50th percentile for the normal range. TT4 increased with age
      in girls (r = 0.25, P < 0.04) but not in boys. FT4 was within normal limits in
      both sexes. TBG measurements were below the 50th percentile and 20% were below
      the 95% CI for both sexes; TT4 correlated with TBG in boys (r = 0.54, P < 0.001)
      and in girls (r = 0.58, P < 0.001). Duration of diabetes had no effect, whereas
      TT4 and FT4 levels were higher in girls with the lowest HbA1 levels (r = -0.29, P
      < 0.01 and r = -0.45, P < 0.01). Levels of TBG were reduced for all male pubertal
      stages (P < 0.01) and for early and late female pubertal stages (P < 0.01). There
      was no direct relationship between glucose control or the duration of diabetes
      and levels of TBG. CONCLUSIONS: Because TT4 levels are low and correlate with the
      low levels of TBG, it is important to measure free thyroid hormone and TSH levels
      in diabetic adolescents to establish euthyroidism.

PMID- 8742569
TI  - The low prevalence of immunogenetic markers in Korean adult-onset IDDM patients.
AB  - OBJECTIVE: IDDM is an autoimmune disease that occurs among genetically
      susceptible individuals. In Asian populations, it is not uncommon for adult
      patients with NIDDM to eventually lose beta-cell function and develop IDDM. These
      individuals may be characterized by autoantibodies to GAD and high-risk HLA-DQ
      alleles, which are unlikely to be prevalent among patients with true NIDDM or in
      the general population. The objective of the present study was to evaluate and
      compare the prevalence of these immunogenetic markers in NIDDM patients and
      healthy nondiabetic individuals from Korea. RESEARCH DESIGN AND METHODS: The
      prevalences of anti-GAD antibodies and HLA-DQA1 and DQB1 alleles among 121
      patients with newly diagnosed NIDDM identified from a population-based study in
      Yonchon, Korea, and 100 matched healthy control subjects were evaluated and
      compared. RESULTS: The overall prevalence of anti-GAD antibodies was 1.7% (2 of
      121) in patients with previously undiagnosed NIDDM, whereas 1 of 100 control
      subjects had a positive test for antibodies. Among those who tested positive,
      titers of antibodies to GAD were not high. No statistically significant
      differences in the distributions of either mean levels of anti-GAD antibodies or
      DQA1 and DQB1 alleles were found comparing NIDDM patients with control subjects.
      Interestingly, the frequency of DQB1*non-Asp-57 and DQA1*Arg-52 alleles in the
      Korean adult control population was similar to that in the U.S. white population
      (DQB1*non-Asp-57: 0.431 vs. 0.475; DQA1*Arg-52: 0.492 vs. 0.463). CONCLUSIONS:
      The low prevalence of anti-GAD antibodies and HLA-DQA1 and DQB1 susceptibility
      alleles among recent-onset NIDDM patients, which was similar to observations in
      control subjects, suggests that diabetes in Korean adults is unlikely to have an
      autoimmune component to its pathogenesis.

PMID- 8742571
TI  - Renal function in long-duration type I diabetes.
AB  - OBJECTIVE: The development of persistent proteinuria is reported to be uncommon
      after 30 years of type I diabetes, and the significance of microalbuminuria in
      patients with long-duration diabetes is unclear. We therefore undertook to study,
      in detail, renal function in patients with long-duration type I diabetes.
      RESEARCH DESIGN AND METHODS: We measured albumin excretion rate (AER), glomerular
      filtration rate (GFR), and serum creatinine in 140 patients with > or = 30 years
      of type I diabetes. We also assessed patients for other micro- macrovascular
      complications of diabetes together with factors implicated in the development of
      diabetic renal disease. RESULTS: Of the patients, 23% had microalbuminuria (AER
      20-200 micrograms/min and/or urinary albumin-to-creatinine ratio [ACR] > 2.5
      mg/mmol [men] or > 3.5 mg/mmol [women] and dipstick negative for proteinuria), 4%
      had overt nephropathy (AER > 200 micrograms/min or persistent dipstick positive
      proteinuria), and 73% were normoalbuminuric (AER < 20 micrograms/min or ACR < 2.5
      mg/mmol [men], < 3.5 mg/mmol [women]). Patients with microalbuminuria had lower
      GFR (81.5 +/- 30.2 vs. 96.0 +/- 20.3 ml.min-1.1.73 m-2; P = 0.06) and higher
      serum creatinine (104 +/- 32 vs. 92 +/- 16 mumol/l; P = 0.06) than those patients
      with normoalbuminuria. Both serum creatinine (P < 0.05) and tobacco consumption
      (P = 0.01) were significantly and independently related to elevated albumin
      excretion. CONCLUSIONS: A substantial proportion of these patients have
      microalbuminuria and evidence of impaired renal function, suggesting that
      progression to end-stage renal failure may still be inevitable. Clinicians should
      continue to monitor renal function in these patients. The relationship between
      tobacco consumption and nephropathy also makes clear the need to reduce cigarette
      smoking in the diabetic population.

PMID- 8742572
TI  - A comparison of acarbose versus metformin as an adjuvant therapy in sulfonylurea
      treated NIDDM patients.
AB  - OBJECTIVE: To compare the effects of acarbose or metformin treatment used as an
      adjunct with a sulfonylurea agent in the treatment of NIDDM not adequately
      controlled with the use of a sulfonylurea agent alone. RESEARCH DESIGN AND
      METHODS: Of the poorly controlled female NIDDM patients on sulfonylurea
      treatment, 18 were randomly selected from the outpatient diabetic clinic for
      study. For 8 weeks, they received either acarbose (300 mg/daily) or metformin
      (1,500 mg/daily) in addition to sulfonylurea in a crossover design using a 3-week
      washout period between treatments. The efficacy of each drug regimen was assessed
      by measuring the levels of glycosylated hemoglobin, fasting and 2-h postprandial
      blood glucose (PPBG) levels, cholesterol, triglyceride, and fibrinogen levels
      before and after 8 weeks of therapy. RESULTS: The metabolic parameters measured
      before initiation of either treatment regimen were similar. Mean fasting and 2-h
      postprandial glucose levels were reduced moderately at the end of 8 weeks of both
      combination treatments (P < 0.05). Although the fasting and 2-h postprandial
      plasma insulin and C-peptide and fibrinogen levels at the end of the 8-week
      treatment periods were lower than those obtained at the beginning of the study,
      the differences between these values were not statistically significant.
      Cholesterol levels remained unchanged. Only the 2-h PPBG level in the group using
      acarbose plus a sulfonylurea was lower than the level achieved by the group using
      metformin plus a sulfonylurea (8.1 +/- 0.8 vs. 9.8 +/- 1.0 mmol/l, respectively,
      P < 0.05). The difference between pre- and posttreatment levels of the 2-h PPBG
      level in both arms of the study were statistically significant (delta-acarbose,
      5.3 +/- 0.4 vs. delta-metformin, 2.9 +/- 0.3) (P < 0.05). Specific drug
      associated side effects were observed in 12 patients on acarbose and 3 patients
      on metformin. CONCLUSIONS: Acarbose or metformin can be used as effective
      adjuvant therapies with a sulfonylurea agent in NIDDM patients who are poorly
      controlled with the sulfonylurea agent alone.

PMID- 8742573
TI  - Human insulin-induced lipoatrophy. Successful treatment using a jet-injection
      device.
AB  - OBJECTIVE: To evaluate the efficacy of the administration of insulin by a jet
      injector device in stopping and reversing severe human insulin-induced
      lipoatrophy. CASE: We report a case of a woman with severe human insulin-induced
      lipoatrophy who has been treated exclusively with recombinant DNA human insulin
      since the onset of IDDM. RESULTS: The loss of subcutaneous tissue in the
      injection areas was demonstrated and measured by high-frequency ultrasound.
      Dermatologic exam demonstrated a severe reduction of fat tissue. After 8 months
      of administration of human insulin by a jet injector, there were no more new
      lesions of lipoatrophy and those affected areas were substantially ameliorated.
      CONCLUSIONS: Jet-injection devices might constitute a helpful method to treat
      those patients affected by severe human insulin-induced lipoatrophy.

PMID- 8742574
TI  - Oxidative stress and diabetic vascular complications.
AB  - Long-term vascular complications still represent the main cause of morbidity and
      mortality in diabetic patients. Although prospective randomized long-term
      clinical studies comparing the effects of conventional and intensive therapy have
      demonstrated a clear link between diabetic hyperglycemia and the development of
      secondary complications of diabetes, they have not defined the mechanism through
      which excess glucose results in tissue damage. Evidence has accumulated
      indicating that the generation of reactive oxygen species (oxidative stress) may
      play an important role in the etiology of diabetic complications. This hypothesis
      is supported by evidence that many biochemical pathways strictly associated with
      hyperglycemia (glucose autoxidation, polyol pathway, prostanoid synthesis,
      protein glycation) can increase the production of free radicals. Furthermore,
      exposure of endothelial cells to high glucose leads to augmented production of
      superoxide anion, which may quench nitric oxide, a potent endothelium-derived
      vasodilator that participates in the general homeostasis of the vasculature. In
      further support of the consequential injurious role of oxidative stress, many of
      the adverse effects of high glucose on endothelial functions, such as reduced
      endothelial-dependent relaxation and delayed cell replication, are reversed by
      antioxidants. A rational extension of this proposed role for oxidative stress is
      the suggestion that the different susceptibility of diabetic patients to
      microvascular and macrovascular complications may be a function of the endogenous
      antioxidant status.

PMID- 8742575
TI  - Accuracy of blood glucose meters in pregnant subjects with diabetes.

PMID- 8742576
TI  - Sex differences in plasma glucose thresholds for counterregulatory hormone
      release and hypoglycemia symptom perception.

PMID- 8742577
TI  - Dialogue between clinicians and researchers will lead to a better diabetes
      classification.

PMID- 8742578
TI  - Oral glucose tolerance tests.

PMID- 8742579
TI  - Genetic variation in the beta3-adrenergic receptor in Japanese NIDDM patients.

PMID- 8742580
TI  - Hypoglycemia and bilateral cortical blindness.

PMID- 8742581
TI  - Insulin resistance and atherosclerosis.

PMID- 8742582
TI  - The insulin resistance syndrome revisited.

PMID- 8742583
TI  - In praise of the hyperglycemic clamp. A method for assessment of beta-cell
      sensitivity and insulin resistance.
AB  - The most widely used methods for the assessment of beta-cell response and
      peripheral tissue sensitivity to insulin include the oral glucose tolerance test
      (OGTT), the frequently sampled intravenous glucose tolerance test, and the
      hyperinsulinemiceuglycemic clamp technique. During an OGTT, glucose levels
      increase after a variable lag period, then reach a peak and fall variably among
      individuals. The response even varies in the same subject upon repeat testing. A
      more reproducible glucose curve is achieved with an intravenous glucose tolerance
      test in which the plasma glucose levels rise rapidly to a very high level and
      fall exponentially. In neither of the two methods is a steady-state glucose level
      achieved. In the hyperinsulinemic-euglycemic clamp technique, a steady-state
      glucose level can be maintained at any level of hyperinsulinemia. However, an
      assessment of beta-cell sensitivity is not obtained. The less used hyperglycemic
      clamp technique can assess beta-cell sensitivity as well as peripheral tissue
      sensitivity. Moreover, a measure of glucose effectiveness or non-insulin-mediated
      glucose uptake can also be determined. With this technique the beta-cells of all
      subjects are stimulated with the same arterial glucose concentration, thus
      enabling assessment of beta-cell response to identical plasma glucose levels.
      Comparison of responses to stable hyperglycemic stimuli can be made in glucose
      tolerant and -intolerant states with the addition of various substances, either
      alone or in combination. The use of the hyperglycemic clamp and several of its
      variant forms is reviewed as an alternative method for assessment of glucose
      homeostasis.

PMID- 8742584
TI  - Insulin resistance and body fat distribution.
AB  - Body fat distribution can be assessed by computed tomography (CT). The ratio of
      umbilicus was used to classify obese subjects as having visceral fat obesity
      (VFO) or subcutaneous fat obesity (SFO). Serum triglyceride and total cholesterol
      levels and plasma glucose area in an oral glucose tolerance test were higher in
      patients with VFO than in those with SFO. Significant positive correlations were
      demonstrated between V/S ratio and plasma glucose area, serum triglyceride level,
      and total cholesterol level as well as systolic or diastolic blood pressure. VFO
      was more frequently associated with coronary artery disease. Moreover, VFO was
      more often accompanied by multiple risk factors than was SFO. Steady-state plasma
      glucose (SSPG) level was significantly higher in patients with VFO than with SFO,
      suggesting that insulin resistance may be more remarkable in VFO than in SFO.
      Furthermore, visceral fat accumulation was also associated with these
      complications even in nonobese subjects. Visceral fat area (VFA) was
      significantly correlated with fasting plasma glucose, serum triglyceride, and
      total cholesterol levels. Animal models such as Goto-Kakizaki (GK) rats with
      ventromedial hypothalamus (VMH) lesions and Otsuka-Long-Evans-Tokushima-Fatty
      (OLETF) rats were accompanied by visceral fat accumulation and an early stage of
      aortic atherosclerosis. Aging, sex hormone, genetic, and dietary factors and
      physical inactivity may induce visceral fat accumulation. Visceral fat is
      characterized by its high lipogenic activity as well as its accelerated lipolytic
      activity. High levels of portal free fatty acids (FFAs) may eventually result in
      an enhancement of hepatic triglyceride synthesis, causing hyperlipidemia. High
      portal FFA levels would also induce insulin resistance, thereby causing glucose
      intolerance, hypertension, and finally atherosclerosis. We propose a term,
      "visceral fat syndrome," as a highly atherogenic state, which includes visceral
      fat accumulation, glucose intolerance (insulin resistance), hyperlipidemia, and
      hypertension.

PMID- 8742585
TI  - Insulin resistance and obesity. The role of fat distribution pattern.

PMID- 8742587
TI  - HIV risk behaviors of heterosexual male drug users.

PMID- 8742586
TI  - New and traditional treatment of glycemia in NIDDM.

PMID- 8742588
TI  - Injection and sexual risk behaviors of male heterosexual injecting drug users.

PMID- 8742589
TI  - HIV/AIDS risks among male, heterosexual noninjecting drug users who exchange
      crack for sex.

PMID- 8742590
TI  - Context of HIV risk behavior among female injecting drug users and female sexual
      partners of injecting drug users.

PMID- 8742591
TI  - Female drug abusers and the context of their HIV transmission risk behaviors.

PMID- 8742592
TI  - Factors associated with sexual risk of AIDS in women.

PMID- 8742593
TI  - Drug use and HIV risk among gay and bisexual men: an overview.

PMID- 8742594
TI  - Substance use and HIV-transmitting behaviors among gay and bisexual men.

PMID- 8742595
TI  - Drug use and HIV risk among male sex workers: results of two samples in San
      Francisco.

PMID- 8742596
TI  - HIV risk in drug-using adolescents.

PMID- 8742597
TI  - HIV risk in adolescents: the role of sexual activity and substance use behaviors.

PMID- 8742598
TI  - Going nowhere fast: methamphetamine use and HIV infection.

PMID- 8742599
TI  - Bringing the context in from the cold: substantive, technical, and statistical
      issues for AIDS research in the second decade.

PMID- 8742600
TI  - The context of risk: ethnographic contributions to the study of drug use and HIV.

PMID- 8742601
TI  - Assessing the reliability and validity of self-reported risk behavior.

PMID- 8742602
TI  - Future directions for studies on the context of HIV risk.

PMID- 8742603
TI  - Therapeutic communities and treatment research.

PMID- 8742604
TI  - The therapeutic community: toward a general theory and model.

PMID- 8742605
TI  - Socialization into the therapeutic community culture.

PMID- 8742606
TI  - Client outcomes from therapeutic communities.

PMID- 8742608
TI  - Predictors of retention in therapeutic communities.

PMID- 8742607
TI  - Retention in therapeutic communities: challenges for the nineties.

PMID- 8742609
TI  - Adolescents in therapeutic communities: retention and posttreatment outcome.

PMID- 8742610
TI  - Therapeutic communities: substance abuse treatment for women.

PMID- 8742611
TI  - Therapeutic communities in prison.

PMID- 8742612
TI  - Co-morbidity and therapeutic community treatment.

PMID- 8742613
TI  - HIV and therapeutic communities.

PMID- 8742614
TI  - Therapeutic communities in corrections and work release: some clinical and policy
      considerations.

PMID- 8742615
TI  - Clinical issues in therapeutic communities.

PMID- 8742616
TI  - Therapeutic community research and practice: recommendations.

PMID- 8742617
TI  - Establishment of the sulfated 3,3'-diiodothyronine radioimmunoassay and its
      application in pregnant women.
AB  - Sulfation of iodothyronines is a major alternate pathway of thyroid hormone
      metabolism during fetal development. Sulfated 3,3'-diiodothyronine (T2S) is a low
      end metabolite of this pathway. Its clinical implications in the prenatal
      evaluation of fetal thyroid disorders are now being intensively investigated. A
      highly sensitive and reproducible radioimmunoassay (RIA) for T2S has been
      established in our laboratory. The detection threshold of the RIA approximated 5
      pg T2S. The dose-response curve of T2S was essentially linear between 5-200 pg.
      An essentially parallel correlation of the dose-response curves for inhibition of
      binding of radiolabeled T2S and T2S antiserum was found between serial dilutions
      of serum extracts and the standards. The average intra- and inter-assay
      coefficients of variation were 7% and 15%, respectively. By applying the T2S RIA,
      we found that serum titers of T2S in pregnant women increased proportionately to
      the gestational age (first trimester vs. second trimester vs. third trimester:
      30.1 +/- 1.4 vs. 41.6 +/- 1.9 vs. 98.0 +/- 3.9 ng/dL; p < 0.001 each). A high
      concentration of T2S was detected in cord and maternal serum at birth as compared
      to the results for non-pregnant women (165.1 +/- 10.3 vs. 113.7 +/- 5.6 vs. 7.5
      +/- 0.9 ng/dL). The T2S levels decreased remarkably in maternal circulation 10
      days after partuition. Four pregnant women who had two blood samplings four or
      more weeks apart during the third trimester showed invariable increases of serum
      T2S titers at later sampling times. Additionally, in the case of a pregnant woman
      who received two doses of T4 injections (200 micrograms/wk) intraamniotically for
      a previous Cretin birth, the maternal serum levels of T2S increased promptly from
      47 ng/dL [corrected] to 96 ng/dL. Our findings imply that the established T2S RIA
      is clinically applicable, provide further evidence that the coincident increase
      of serum T2S titers in pregnant women may reflect ontogenesis of fetal thyroid
      hormone maturation, and provide a clue to the fetal thyroid status in the
      prenatal stage. However, more knowledge is still needed regarding the transfer
      and transformation of sulfated iodothyronine(s) from the fetal compartment to
      maternal circulation.

PMID- 8742618
TI  - Isolation and cultivation of aortic endothelial cells from spontaneously
      hypertensive rat with a modified tissue explant technique.
AB  - In the present study, we successfully established a "tissue explant technique" to
      obtain high yield and purity of endothelial cells from the aorta of hypertensive
      and normotensive rats (SHR and WKY). Small pieces of aorta were placed on
      fibronectin precoated petri dishes. The effects of oxygenation in the tissue
      preparation stage, tilting of the petri dish during the explanting period and
      timing of the removal of tissue blocks from petri dishes were evaluated. These
      procedures appeared to be critical for cell survival, tissue adhesion and
      minimizing of non-endothelial cell contamination. The cultured endothelial cells
      were characterized by morphological, immunohistochemical and biochemical
      examination. The cultured cells from both SHR and WKY rats showed similar
      endothelial cell character, positive immunofluorescence staining for the von
      Willebrand factor, and uptake of acetylated low-density lipoprotein (DiI-ac-LDL).
      The secretory function of prostacylcin I2 (PGI2), thromboxane A2 and endothelin
      of cultured endothelial cells was measured. The results showed that the secretion
      of both PGI2 and endothelin was greater in SHR than in WKY rats, but that there
      was no difference in thromboxane A2 secretion. Therefore, our "tissue explant
      technique" can provide high yield and purity of endothelial cells with their
      specific biological function in vitro. It will permit us to further study the
      role of endothelial cells in the development of hypertension.

PMID- 8742619
TI  - Production of lytic enzyme from Pseudomonas aeruginosa M-1001.
AB  - Pseudomonas aeruginosa M-1001 produced both hen-egg-white lysozyme inhibitors and
      lytic enzyme in the culture broth. The lytic enzyme produced was not inhibited by
      the lysozyme inhibitors. Maximal lytic activity was obtained when the strain was
      grown aerobically in a medium consisting of 0.25% glucose, 0.75% soluble strach,
      0.25% beef extract, 0.25% Polypepton, 0.25% sodium L-glutamate and 0.0001% NaCl
      (pH 6), at 37 degrees C after 36 hrs. The lytic enzyme was stable at pH from 6 to
      8 and temperatures below 40 degrees C. Many bacteria and Saccharomyces cerevisiae
      were found to be inhibited by the crude lytic enzyme produced from the M-1001
      strain except for the strain itself and a few other microorganisms.

PMID- 8742620
TI  - Production of the third component of complement (C3) by peripheral
      polymorphonuclear neutrophils of the patients with rheumatoid arthritis.
AB  - Normal human polymorphonuclear neutrophils (PMN) can spontaneously produce the
      third component of complement (C3) in in vitro culture as detected by ELISA. This
      C3-producing capacity of PMN can be augmented by TNF-alpha (20 ng/ml) and
      bacterial lipopolysaccharide (100 ng/ml), but not by IL-1 beta or IL-8. The C3
      production by PMN was found to be temperature dependent and was suppressed by the
      addition of protein inhibitor. The C3 mRNA in PMN could be detected by reverse
      transcription assisted polymerase chain reaction (RT-PCR) after TNF-alpha or LPS
      stimulation for 6 hours. To further understand C3 production by peripheral blood
      PMN in rheumatoid arthritis (RA), spontaneous and TNF-alpha stimulated production
      of C3 by peripheral PMN were compared in 15 cases of active RA, 15 inactive RA
      and 15 normal individuals. We failed to find any significant difference among the
      three groups. We conclude that PMN plays a negligible role in C3
      hypercomplementemia in patients with active RA.

PMID- 8742621
TI  - Mitochondrial alterations of skeletal muscle in a heat stress rat model.
AB  - The morphological and ultrastructural alterations of skeletal muscle in
      experimental rats with heat stress were investigated. Fifteen male Sprague-Dawley
      rats were exposed in a 42 degrees C constant temperature oven, resulting in a
      heat stress state; ten rats were used as controls. All treated rats had weakness
      of the 4 limbs associated with increased serum creatine kinase levels (p < 0.01).
      Soleus muscles were submitted to histological, histochemical, ultrastructural and
      quantitative-morphometric analysis. The group receiving heat stress showed many
      ragged-red fibers in Gomori trichrome stain and appeared hyper-reactive in
      succinate dehydrogenase and cytochrome C oxidase stains. The ultrastructure of
      ragged-red fibers showed increased mitochondrial aggregation as multiple small
      nests, which were particularly located in the subsarcolemmal space. The
      mitochondrial area was significantly increased in heat stress rats (p < 0.001).
      The consistently increased mitochondrial area and histochemical alterations of
      mitochondria are early pathological abnormalities in muscles with heat stress and
      indicate fundamental impairment of energy metabolism.

PMID- 8742622
TI  - Portal hemodynamics and humoral factors involved in a portal hypertensive rabbit
      model.
AB  - Hemodynamic changes and certain humoral factors possibly responsible for
      splanchnic hyperemia in portal hypertensive rabbits created by partial portal
      vein ligation were studied. Portal pressure was significantly elevated after
      portal vein ligation and reached a climax on the second day. Then, it decreased
      but still remained at a plateau in a portal hypertensive state in the following
      days. Portal blood flow, measured with an electromagnetic flowmeter, had no
      significant change immediately after portal vein ligation and on post ligation
      day-1, but it increased significantly from the second day. Portal venous
      resistance rose significantly from the basal state immediately after portal vein
      ligation, then, it decreased from the second day, but still remained at a high
      resistance level as compared with the normal (p < 0.05). The levels of
      prostaglandin E2 and prostacyclin in the portal vein increased immediately after
      portal vein ligation but decreased on the second day. However, prostacyclin rose
      again on the fifth day. It is apparent from this study that once portal pressure
      or portal resistance increases, there is a surge of prostaglandin E2 and
      prostacyclin in the portal blood. Due to the vasodilation effect of prostacyclin,
      prostaglandin E2 and other possible vasodilators, portosystemic shunts are
      gradually produced, and splanchnic hyperemia develops in the portal hypertension.
      The initial mechanism of portal hypertension in this model was due mainly to an
      increase in resistance. At a later stage, increased splanchnic blood flow
      combined with increased resistance played an important role in the maintenance of
      portal hypertension.

PMID- 8742623
TI  - Changes of dentinal tubules following fluoride iontophoresis.
AB  - Fluoride(F) iontophoresis is preferred over topical application to provide long
      lasting dentin desensitization. The purpose of this study was to evaluate the
      changes in dentinal tubules following fluoride iontophoresis under SEM
      observation. Teeth were divided mainly into 3 groups: controls, NaF treated teeth
      with iontophoresis and those without inotophoresis. A battery operated device was
      used to apply electric current to teeth. All the teeth were prepared for scanning
      electron microscopy after treatments. Fluoride treatment, either non
      iontophoretic or iontophoretic, produced granular precipitation in dentinal
      tubules and reduced tubular diameter. In 5-minute non-iontophoretic NaF treated
      teeth, the depth of precipitate penetration was 75 microns on average where the
      granules were small and sparse. In the 5-minute iontophoretic NaF treated teeth,
      the average penetration of precipitation reached 250 microns in one application
      whereas in three applications to teeth the average depth of penetration reached
      830 microns. Fluoride iontophoresis resulted in obstruction of dentinal tubules.
      Both the frequency and duration od treatment under constant current and voltage
      affected the size of particles, the form of precipitation and the depth of
      penetration. Larger particle size and deeper fluoride penetration were observed
      in iontophoresis treated teeth compared to non-iontophoresis treated teeth.
      Therefore, repeated fluoride iontophoresis treatment is suggested to ensure long
      lasting densensitization effects.

PMID- 8742624
TI  - [The ipriflavone story].
AB  - Ipriflavone is an original molecule. Its introduction took a complicated course
      first in veterinary use as a fodder additive then after checking out its
      antianginal effects it was registered and launched as an effective osteoporotic
      agent first in Japan 1988 nineteen years after the elaboration of the synthesis
      of the active ingredient. Dr. Laszlo Feuer who started and managed the research
      died after a short sickness in 1984 and so didn't live to see the success of
      ipriflavone.

PMID- 8742625
TI  - [Synthesis of isoflavones].
AB  - Construction of isoflavon skeleton is the keystep in the ipriflavon synthesis.
      Preparation of isoflavons is widely covered through the intermediats 2
      hydroxyphenyl benzyl ketone and 2-hydroxychalcone. Other synthetic methods are
      also described.

PMID- 8742626
TI  - [Forced stability study of ipriflavone].
AB  - Forced stability study of ipriflavone has been conducted on solid state and in
      solution using different chromatographic techniques (TLC, HPLC, LC-TSP-MS) for
      measurement and identification. In solid state effect of high temperature, UV
      irradiation and that of artificial daylight were studied. In solution
      susceptibility to hydrolysis and oxidative ability were investigated. It was
      found that ipriflavone is stable in solid form at high temperature and against UV
      and daylight irradiation. In solution at high pH (pH > or = 9) ipriflavone is
      hydrolized and (2-hydroxy-4-isopropoxy-phenyl)benzyl-ketone develops as the main
      degradation product. Using hydrogen-peroxide or alpha,alpha'-asoisobutyronitrile
      ipriflavone can be oxidized, developing 2,3-dihydro-2,3-oxo-ipriflavone.

PMID- 8742627
TI  - [Characterization of ipriflavone structure by instrumental examination].
AB  - The elucidation of the chemical structure of lpriflavone was carried out by
      ultraviolet absorption spectrophotometric, infrared spectroscopic, 1H and 13C
      nuclear magnetic resonance spectroscopic, low and high resolution EI mass
      spectrometric, thermoanalytical, elemental analytical and X-ray diffraction
      methods. The results unambigously verify the structure of Ipriflavone.

PMID- 8742628
TI  - [Metabolism of ipriflavone].
AB  - Ipriflavone is intensively metabolized by the organism, due to strong first-pass
      metabolism only a small fraction of the dose absorbed is unchanged Ipriflavone.
      Seven metabolites were identified in animal as well as in human studies.
      Ipriflavone is metabolized exclusively in the liver by elimination, or oxidation
      of the isopropyl group and hydroxylation of the beta-ring followed by conjugation
      with glucuronic and/or sulphuric acid. In animals 7-hydroxy-isoflavone (M1) was
      the main metabolite of Ipriflavone, while in man 7-(1-carboxy-ethoxy)-isofla-vone
      (M5). There was no sex-difference in the metabolism of Ipriflavone either in
      animal, or in human studies.

PMID- 8742629
TI  - [Pharmacokinetics of ipriflavone].
AB  - Ipriflavone administered to rats orally is well absorbed from small intestine via
      the portal route, distributed widely in tissues, metabolized extensively by
      oxidation, and eliminated from the body preferentially in urine. The absorption
      of ipriflavone is less effective in dogs, than in rats. In dogs, the compound
      absorbed is metabolized in the same way as in rats and the metabolites formed are
      eliminated largely in faeces, together with unabsorbed ipriflavone. In human,
      ipriflavone administered orally is rapidly absorbed, and quickly metabolized. The
      dose is eliminated mainly via the urinary route as metabolites (57% of the dose),
      and the smaller fraction with the faeces, mostly as ipriflavone (40% of the
      dose). There is no significant change in the pharmacokinetics of ipriflavone even
      after multiple dose. In the serum, ipriflavone and its metabolites are primarily
      bound to albumin, the binding is 94-99% and totally reversible.

PMID- 8742630
TI  - [Overview of clinical studies with ipriflavone].
AB  - Since the discovery and preclinical testing numerous clinical trials have been
      performed with ipriflavone. It seems that four basic periods of time could be
      considered as steps of clinical development. Between the late seventies and early
      eighties the first steps have been taken in Hungary. Based on the promising
      results clinical studies were performed in Japan by Takeda. Since ipriflavone has
      proved to be efficacious in preventing bone loss the drug had been registered in
      Japan. In the late eighties the clinical development started in Italy by Chiesi.
      As the results were similarly positive ipriflavone has been registered in 1991.
      Realizing the important changes both in the scientific and regulatory fields
      Chinoin itself and also in cooperation with Chiesi has been continuing the
      clinical development process in order to fulfill the presently generally accepted
      criteria.

PMID- 8742631
TI  - [Place of ipriflavone in the therapy of osteoporosis].
AB  - In Hungary ipriflavone has been marketed under the name Osteochin. After a short
      summary of the clinically proven results the article tries to position
      ipriflavone among antiosteoporotic drugs. Not only on the basis of preclinical
      results the article shows that Osteochin--as a non hormonal agent--can be given
      to those patients who can not receive hormone replacement therapy, there are
      grounds for giving combination of ipriflavone and a low dose estrogen.
      Ipriflavone's advantages are that it decreases acute and chronic back pain due to
      osteoporosis, it is rapidly metabolized and is quickly eliminated therefore it
      can not cause any long acting side effects, patients' compliance is good.
      Ipriflavone, the original Hungarian compound is an alternative possibility in the
      treatment of osteoporosis.

PMID- 8742632
TI  - Majority-rule reduced consensus trees and their use in bootstrapping.
AB  - Bootstrap analyses are usually summarized with majority-rule component consensus
      trees. This consensus method is based on replicated components and, like all
      component consensus methods, it is insensitive to other kinds of agreement
      between trees. Recently developed reduced consensus methods can be used to
      summarize much additional agreement on hypothesised phylogenetic relationships
      among multiple trees. The new methods are "strict" in the sense that they require
      agreement among all the trees being compared for any relationships to be
      represented in a consensus tree. Majority-rule reduced consensus methods are
      described and their use in bootstrap analyses is illustrated with a hypothetical
      and a real example. The new methods provide summaries of the bootstrap
      proportions of all n-taxon statements/partitions and facilitate the
      identification of hypotheses of relationships that are supported by high
      bootstrap proportions, in spite of a lack of support for particular components or
      clades. In practice majority-rule reduced consensus profiles may contain many
      trees. The size of the profile can be reduced by constraints on minimal bootstrap
      proportions and/or cardinality of the included trees. Majority-rule reduced
      consensus trees can also be selected a posteriori from the profile. Surrogates to
      the majority-rule reduced consensus methods using partition tables or tree
      pruning options provided by widely used phylogenetic inference software are also
      described. The methods are designed to produce more informative summaries of
      bootstrap analyses and thereby foster more informed assessment of the strengths
      and weaknesses of complex phylogenetic hypotheses.

PMID- 8742633
TI  - Early origin of foraminifera suggested by SSU rRNA gene sequences.
AB  - Foraminifera are one of the largest groups of unicellular eukaryotes with
      probably the best known fossil record. However, the origin of foraminifera and
      their phylogenetic relationships with other eukaryotes are not well established.
      In particular, two recent reports, based on ribosomal RNA gene sequences, have
      reached strikingly different conclusions about foraminifera's evolutionary
      position within eukaryotes. Here, we present the complete small subunit (SSU)
      rRNA gene sequences of three species of foraminifera. Phylogenetic analysis of
      these sequences indicates that they branch very deeply in the eukaryotic
      evolutionary tree: later than those of the amitochondrial Archezoa, but earlier
      than those of the Euglenozoa and other mitochondria-bearing phyla. Foraminifera
      are clearly among the earliest eukaryotes with mitochondria, but because of the
      peculiar nature of their SSU genes we cannot be certain that they diverged first,
      as our data suggest.

PMID- 8742634
TI  - Sequence heterogeneities among 16S ribosomal RNA sequences, and their effect on
      phylogenetic analyses at the species level.
AB  - We have analyzed what phylogenetic signal can be derived by small subunit rRNA
      comparison for bacteria of different but closely related genera (enterobacteria)
      and for different species or strains within a single genus (Escherichia or
      Salmonella), and finally how similar are the ribosomal operons within a single
      organism (Escherichia coli). These sequences have been analyzed by neighbor
      joining, maximum likelihood, and parsimony. The robustness of each topology was
      assessed by bootstrap. Sequences were obtained for the seven rrn operons of E.
      coli strain PK3. These data demonstrated differences located in three highly
      variable domains. Their nature and localization suggest that since the divergence
      of E. coli and Salmonella typhimurium, most point mutations that occurred within
      each gene have been propagated among the gene family by conversions involving
      short domains, and that homogenization by conversions may not have affected the
      entire sequence of each gene. We show that the differences that exist between the
      different operons are ignored when sequences are obtained either after cloning of
      a single operon or directly from polymerase chain reaction (PCR) products. Direct
      sequencing of PCR products produces a mean sequence in which mutations present in
      the most variable domains become hidden. Cloning a single operon results in a
      sequence that differs from that of the other operons and of the mean sequence by
      several point mutations. For identification of unknown bacteria at the species
      level or below, a mean sequence or the sequence of a single nonidentified operon
      should therefore be avoided. Taking into account the seven operons and therefore
      mutations that accumulate in the most variable domains would perhaps increase
      tree resolution. However, if gene conversions that homogenize the rRNA multigene
      family are rare events, some nodes in phylogenetic trees will reflect these
      recombination events and these trees may therefore be gene trees rather than
      organismal trees.

PMID- 8742635
TI  - Loculoascomycete origins and evolution of filamentous ascomycete morphology based
      on 18S rRNA gene sequence data.
AB  - The fungal subclass Loculoascomycetes is characterized by asci or sexual spore
      sacks with two separable wall layers. At maturity, the inner wall layer protrudes
      out beyond the outer wall as in a jack-in-the-box. If the Loculoascomycetes were
      monophyletic and their jack-in-the-box type asci evolved once, then taxa from
      diverse loculoascomycete lineages would cluster together in a DNA sequence-based
      tree. To evaluate the phylogenetic history of the two-walled asci, I sequenced
      the 18S nuclear rRNA genes of 16 species from seven families in the
      loculoascomycete orders Pleosporales, Dothideales, and Chaetothyriales. Within
      the Loculoascomycetes, the Pleosporales form a monophyletic group in 99% of the
      bootstrapped parsimony trees. The Dothideales usually appear as a monophyletic
      group but without statistical support. Capronia pilosella (Herpotrichiellaceae,
      Order Chaetothyriales) clusters with plectomycete members of the subclass
      Euascomycetes rather than the other Loculoascomycetes in 99% of parsimony and
      neighbor-joining bootstrap replicates. Although the jack-in-the-box-type ascus is
      a good marker for large, monophyletic loculoascomycete orders, it must have
      evolved at least twice or been lost at least once.

PMID- 8742636
TI  - Length variation and secondary structure of introns in the Mlc1 gene in six
      species of Drosophila.
AB  - A nearly universal feature of intron sequences is that even closely related
      species exhibit a large number of insertion/deletion differences. The goal of the
      analysis described here is to test whether the observed pattern of
      insertion/deletion events in the genealogy of the myosin alkali light chain
      (Mlc1) gene is consistent with neutrality, and if not, to determine the
      underlying forces of evolutionary change. Mlc1 pre-mRNA is alternatively spliced,
      and one constraint is that signals necessary for tissue-specificity of directed
      splicing must be conserved. If the total length of an intron is functionally
      constrained, then the distribution of indels on branches of the gene genealogy
      should reflect a departure from randomness. Here we perform a phylogenetic
      analysis, inferring ancestral states wherever possible on a phylogeny of 29
      alleles of Mlc1 from six species of Drosophila. Observed patterns of indels on
      the genealogy were compared to those from simulated data, with the result that we
      cannot reject the null hypothesis of neutrality. A clear departure from a neutral
      prediction was seen in the excess folding free energy predicted for the introns
      flanking the alternatively spliced exon. Relative rate tests also suggest a
      retardation in the rate of Mlc1 sequence evolution in the simulans clade.

PMID- 8742637
TI  - Evolution of gene families and relationship with organismal evolution: rapid
      divergence of tissue-specific genes in the early evolution of chordates.
AB  - To determine a possible relationship between organismal and molecular evolution,
      the divergence patterns of gene families were examined by taking special notice
      of functional difference, tissue distribution, and intracellular localization of
      the members. A phylogenetic analysis of 25 different gene families revealed
      interesting patterns of divergence of these families: Most gene duplications
      giving rise to different functions antedate the vertebrates-arthropods
      separation. On the other hand, in a group of members carrying virtually identical
      function to one another but differing in tissue distribution (tissue-specific
      isoform), most gene duplications have occurred independently in each of
      vertebrates and arthropods after the separation of the two animal groups. In
      family members encoding molecules localizing in cell compartments
      (compartmentalized isoforms), the gene duplications antedate the animals-fungi
      separation. In the cases of the Ca2+ pump and rab subfamilies, the
      compartmentalized isoforms were shown to have diverged during the early evolution
      of eukaryotes. A phylogenetic analysis of the tissue-specific isoforms from 26
      different subfamilies revealed extensive gene duplications and rapid rates of
      amino acid substitutions in the early evolution of chordates before the
      separation of fishes and tetrapods. On the contrary, the genetic variations are
      relatively low in the later period. This pattern of evolution observed at the
      molecular level is correlated well with that of tissue evolution based on fossil
      evidence and morphological data, and thus evolution at the two levels may be
      related.

PMID- 8742638
TI  - The impact of population expansion and mutation rate heterogeneity on DNA
      sequence polymorphism.
AB  - In order to study the effect of mutation rate heterogeneity on patterns of DNA
      polymorphism, we simulated samples of DNA sequences with gamma-distributed
      nucleotide substitution rates in stationary and expanding populations. We find
      that recent population expansions and mutation rate heterogeneity have similar
      effects on several polymorphism indicators, like the shape and the mean of the
      observed pairwise difference distribution, or the number of segregating sites.
      The inferred size of population expansion thus appears overestimated if
      nucleotides have dissimilar substitution rates. Interestingly, population
      expansion and uneven mutation rates have contrasting effects on Tajima's D
      statistic when acting separately, and the consequence on the associated test of
      selective neutrality is investigated. The patterns of polymorphism of several
      human populations analyzed for the mitochondrial control region are examined,
      mainly showing the difficulty in quantifying the respective contribution of past
      demographic history and uneven mutation rates from a single sampled evolutionary
      process. However, substitution rates appear more heterogeneous in the second
      hypervariable segment of the control region than in the first segment.

PMID- 8742639
TI  - A nonlinear method for estimating nucleotide polymorphism from restriction maps.
AB  - Restriction mapping is used to estimate nucleotide sequence polymorphism when the
      regions to be studied are too long or too numerous to be sequenced. Restriction
      mapping is less costly than DNA sequencing, but it does not allow direct
      measurement of underlying nucleotide polymorphism. It is therefore useful to be
      able to estimate underlying nucleotide polymorphism from observations of
      polymorphism in restriction maps, as this offers some of the resolution afforded
      by DNA sequencing at a reduced cost. Previous estimators of underlying nucleotide
      polymorphism have assumed that each restriction-enzyme-binding site contains, at
      most, a single polymorphic nucleotide position (the low-polymorphism-frequency
      assumption), and this assumption has placed an upper limit on the level of
      polymorphism that can be resolved by these estimators. The present study
      documents an estimator which allows relaxation of this assumption. The new
      estimator more accurately estimates underlying nucleotide polymorphism when the
      polymorphism level is high enough to falsify the low-polymorphism-frequency
      assumption. The new estimator therefore yields good results for data sets that
      are too divergent for analysis by present methods.

PMID- 8742640
TI  - Numerous transposed sequences of mitochondrial cytochrome oxidase I-II in aphids
      of the genus Sitobion (Hemiptera: Aphididae).
AB  - Polymerase chain reaction (PCR) products corresponding to 803 bp of the
      cytochrome oxidase subunits I and II region of mitochondrial DNA (mtDNA COI-II)
      were deduced to consist of multiple haplotypes in three Sitobion species. We
      investigated the molecular basis of these observations. PCR products were cloned,
      and six clones from one individual per species were sequenced. In each
      individual, one sequence was found commonly, but also two or three divergent
      sequences were seen. The divergent sequences were shown to be nonmitochondrial by
      sequencing from purified mtDNA and Southern blotting experiments. All seven
      nonmitochondrial clones sequenced to completion were unique. Nonmitochondrial
      sequences have a high proportion of unique sites, and very few characters are
      shared between nonmitochondrial clones to the exclusion of mtDNA. From these
      data, we infer that fragments of mtDNA have been transposed separately (probably
      into aphid chromosomes), at a frequency only known to be equalled in humans. The
      transposition phenomenon appears to occur infrequently or not at all in closely
      related genera and other aphids investigated. Patterns of nucleotide substitution
      in mtDNA inferred over a parsimony tree are very different from those in
      transposed sequences. Compared with mtDNA, nonmitochondrial sequences have less
      codon position bias, more even exchanges between A, G, C and T, and a higher
      proportion of nonsynonymous replacements. Although these data are consistent with
      the transposed sequences being under less constraint than mtDNA, changes in the
      nonmitochondrial sequences are not random: there remains significant position
      bias, and probable excesses of synonymous replacements and of conservative
      inferred amino acid replacements. We conclude that a proportion of the inferred
      change in the nonmitochondrial sequences occurred before transposition. We
      believe that Sitobion aphids (and other species exhibiting mtDNA transposition)
      may be important for studying the molecular evolution of mtDNA and pseudogenes.
      However, our data highlight the need to establish the true evolutionary
      relationships between sequences in comparative investigations.

PMID- 8742641
TI  - Efficiencies of different genes and different tree-building methods in recovering
      a known vertebrate phylogeny.
AB  - The relative efficiencies of different protein-coding genes of the mitochondrial
      genome and different tree-building methods in recovering a known vertebrate
      phylogeny (two whale species, cow, rat, mouse, opossum, chicken, frog, and three
      bony fish species) was evaluated. The tree-building methods examined were the
      neighbor joining (NJ), minimum evolution (ME), maximum parsimony (MP), and
      maximum likelihood (ML), and both nucleotide sequences and deduced amino acid
      sequences were analyzed. Generally speaking, amino acid sequences were better
      than nucleotide sequences in obtaining the true tree (topology) or trees close to
      the true tree. However, when only first and second codon positions data were
      used, nucleotide sequences produced reasonably good trees. Among the 13 genes
      examined, Nd5 produced the true tree in all tree-building methods or algorithms
      for both amino acid and nucleotide sequence data. Genes Cytb and Nd4 also
      produced the correct tree in most tree-building algorithms when amino acid
      sequence data were used. By contrast, Co2, Nd1, and Nd41 showed a poor
      performance. In general, large genes produced better results, and when the entire
      set of genes was used, all tree-building methods generated the true tree. In each
      tree-building method, several distance measures or algorithms were used, but all
      these distance measures or algorithms produced essentially the same results. The
      ME method, in which many different topologies are examined, was no better than
      the NJ method, which generates a single final tree. Similarly, an ML method, in
      which many topologies are examined, was no better than the ML star decomposition
      algorithm that generates a single final tree. In ML the best substitution model
      chosen by using the Akaike information criterion produced no better results than
      simpler substitution models. These results question the utility of the currently
      used optimization principles in phylogenetic construction. Relatively simple
      methods such as the NJ and ML star decomposition algorithms seem to produce as
      good results as those obtained by more sophisticated methods. The efficiencies of
      the NJ, ME, MP, and ML methods in obtaining the correct tree were nearly the same
      when amino acid sequence data were used. The most important factor in
      constructing reliable phylogenetic trees seems to be the number of amino acids or
      nucleotides used.

PMID- 8742642
TI  - Mitochondrial DNA migration events in yeast and humans: integration by a common
      end-joining mechanism and alternative perspectives on nucleotide substitution
      patterns.
AB  - In contrast to extensive infiltration of plant nuclear genomes by mitochondrial
      and chloroplast DNA fragments, a computer assessment method could only detect
      seven mitochondrial DNA integration events in Saccharomyces cerevisiae
      chromosomes and five examples of DNA migration into mammalian nuclear genes. No
      evidence could be detected for mitochondrial DNA insertion into chromosome III of
      Caenorhabditis elegans or in nuclear DNA sequences of Drosophila sp. or
      Plasmodium falciparum. Thus, the quantity of organellar DNA in the nucleus
      appears to vary amongst organisms and is lower in Saccharomyces cerevisiae than
      suggested by experimental plasmid systems. As in plants, migratory mitochondrial
      DNA fragments in yeast and mammals are found in intergenic regions and introns.
      Although many of these insertions are located near retroelements, mitochondrial
      DNA incorporation appears to be independent of retroelement insertion. Comparison
      of the mitochondrial DNA fragments with mitochondrial transcription maps suggest
      that two fragments may have transposed through DNA-based and one through RNA
      based mechanisms. Analyses of the integration sites indicate that organellar DNA
      sequences are incorporated by an end-joining mechanism common to yeast, mammals,
      and plants. The transferred sequences also provide a novel perspective on rates
      and patterns of nucleotide substitution. Analysis of the D-loop region including
      a nuclear copy of mitochondrial DNA supports a progressive reduction in D-loop
      length within both monkey and great apes mitochondrial lineages. Relative
      distance tests polarized with nuclear copies of the mitochondrial 12S/16S rRNA
      region suggest that a constant number of transversions has accumulated within the
      great ape clade, but the number of transitions in orangutan is elevated with
      respect to members of the human/chimp/gorilla clade. In addition to DNA migration
      events, 29 nuclear/mitochondrial genes were identified in GenBank that appear to
      result from inadvertent ligation of nuclear and mitochondrial mRNA transcripts
      during the cloning process.

PMID- 8742643
TI  - Psychologic predictors of duodenal ulcer healing.
AB  - We investigated psychologic influences on duodenal ulcer by examining the effect
      of personality, stress, and mood, measured at diagnosis, on subsequent ulcer
      healing. Stressful life events, psychopathology (assessed using the Minnesota
      Multiphasic Personality Inventory), anxiety, depression, smoking, alcohol
      consumption, nonsteroidal antiinflammatory drug use, and serum pepsinogen I
      levels were determined immediately after endoscopy showed duodenal ulcer craters
      in 70 patients with recent onset of symptoms. Endoscopy was repeated following 6
      weeks of ranitidine therapy. Six ulcers (8.6%) persisted, and the duodenum
      remained inflamed in an additional five cases, for a total of 16% with incomplete
      healing. The only baseline characteristic significantly associated with poor
      healing was anxiety (p = 0.03 for ulcer persistence, p = 0.02 for incomplete
      healing). Being in the highest anxiety tertile was associated with a more than
      fourfold elevation in the risk of incomplete healing (p = 0.02). The association
      between anxiety and poor healing was not changed by modification of the anxiety
      score to eliminate gastrointestinal symptom items or by adjustment for serum
      pepsinogen, sex, or cigarette smoking. Anxiety inhibits the healing of duodenal
      ulcers treated with adequate antisecretory therapy.

PMID- 8742644
TI  - Basal and stimulated gastrin levels and gastric acid output five months after
      therapy for Helicobacter pylori eradication in duodenal ulcer patients.
AB  - The aim of our study was to demonstrate the effect of Helicobacter pylori
      eradication on basal and stimulated serum gastrin levels and gastric acid output
      5 months after therapy of patients with duodenal ulcer. Thirty-two patients (24
      men and eight women with a mean age of 45 years) who had had endoscopy and were
      diagnosed as having duodenal ulcer entered the study. In all patients three
      biopsy specimens were taken from the duodenal bulb, gastric antrum, body, and
      fundus. These specimens were then sent for microbiological and histological
      examination. Triple therapy consisting of bismuth, metronidazole, and
      tetracycline was administered. Endoscopy was repeated 1 and 5 months after
      therapy, and biopsy specimens were again taken from the gastric antrum and body.
      Before treatment, serum samples were taken to measure basal and stimulated (90
      min) gastrin levels after ingestion of two beef cubes, and basal and stimulated
      acid outputs (after pentagastrin) were studied. Measurements of gastrin and
      gastric acid output were repeated 5 months after therapy. H. pylori was
      eradicated in 26 patients (81.3%). Basal gastrin levels (mean +/- SD) at
      diagnosis and after eradication were 44 +/- 12 and 35.8 +/- 2 pg/ml, respectively
      (p < 0.05). Similarly, stimulated gastrin levels (integrated values) decreased
      from 5,303 +/- 1,526 pg/ml/min before therapy to 3,779 +/- 1,204 pg/ml/min after
      eradication (p < 0.001). However, basal (4.9 +/- 4mEq/h) and stimulated (28.5 +/-
      10mEq/h) acid output did not vary after eradication (3.9 +/- 4 mEq/h and 26.2 +/-
      12 mEq/h, respectively). We conclude that basal and stimulated gastric acid
      output are not changed by H. pylori eradication in duodenal ulcer patients 5
      months after therapy, in spite of its association with a significant decrease in
      basal and stimulated gastrin levels.

PMID- 8742645
TI  - Reversible prolonged skin bleeding time in acute gastrointestinal bleeding
      presumed due to NSAIDs.
AB  - The purpose of this research was to look for a possible mechanism whereby NSAIDs,
      and particularly ASA, might cause gastrointestinal bleeding. A total of 34
      hospitalized GI bleeders and 29 age- and sex-matched controls were studied. Skin
      bleeding time (SBT) was measured within 6 h of coming to hospital and before any
      blood products were given. All patients and controls were questioned regarding
      current NSAID use. This history was supplemented by estimation of serum
      salicylate and of platelet cyclooxygenase activity to detect unreported current
      aspirin (ASA) use. Various aspects of platelet function were also tested by
      lumiaggregation in 28 controls and, after recovery, in 27 of the bleeders. Of 34
      bleeders, 26 bled from the upper GI tract, (13 from peptic ulcer) and eight from
      the lower GI tract, 30 (88%) had a current intake of NSAIDs and of these 22 (73%)
      used ASA, some in combination with other NSAIDs, whereas 12 of 29 controls were
      using NSAID's, 11 of which were ASA. SBT in the bleeders was 9.0 +/- 1.02 min
      versus 4.8 +/- 0.42 min in the controls (p < 0.001). SBT measured 6.6 days later
      in 28 bleeders was 4.7 +/- 0.22 min (p < 0.0006), and of those tested after
      recovery all but one had fallen to 6.5 min or less. None had any residual
      constitutional platelet abnormalities as tested by lumiaggregation. By logistic
      regression, NSAID intake was strongly associated with prolonged SBT to > 6 min
      (odds ratio [OR], 16.7; p < 0.0002), whereas NSAID intake (OR 14.6; p < 0.0003)
      and SBT > 6 min (OR 1.8; p < 0.005) contributed to a bleeding outcome. Almost 90%
      of GI bleeders had recently consumed NSAIDs, mostly ASA, on an average 15 h
      before onset of bleeding. Although most of the nonbleeders who had used NSAIDs
      did not have a prolonged SBT, most of the bleeders who used NSAIDs had an
      abnormal elevation of SBT, suggesting a possible mechanism for GI bleeding.
      Retesting approximately 7 days after recovery from bleeding showed normalization
      of the SBT, indicating that the defect was transient and spontaneously
      reversible.

PMID- 8742646
TI  - Endoscopic ultrasound in the diagnosis of watermelon stomach.
AB  - We describe three cases of watermelon stomach in which the endoscopic appearance
      suggested the diagnosis, which was confirmed by histologic examination. The
      diagnosis was further substantiated by endoscopic ultrasound imaging.

PMID- 8742647
TI  - Soluble CD44 isoforms in serum as potential markers of metastatic gastric
      carcinoma.
AB  - A splice variant of CD44 (exon V4-V7) confers metastatic behavior in a rat
      carcinoma model; aberrant expression of splice variants has been detected on a
      variety of human tumor cell lines as well as primary and metastatic human tumors,
      including lymphomas, carcinomas (colon, thyroid, mamma, bladder), and glioma. We
      used enzyme-linked immunosorbent assay to determine the concentration of soluble
      CD44 in the serum samples of 10 normal individuals and 41 patients with various
      stages of gastric cancer. Soluble CD44S and its isoforms, V5 and V6, were present
      in the serum of normal individuals (288.53 +/- 18.33, 25.49 +/- 1.70, and 148.32
      +/- 3.15 ng/ml, respectively). The concentrations of soluble CD44 V5 and V6 were
      elevated in patients with advanced gastric carcinoma (69.39 +/- 6.06 and 216.62
      +/- 32.98 ng/ml, respectively). Serum CD44 V5 concentrations correlated with the
      extent of tumor invasion (T), the status of lymph node involvement (N), and
      distant metastasis (M) (TNM staging) (p < 0.05), whereas CD44S did not. These
      results suggest that detection of abnormal regulation of CD44 splicing could be
      helpful in gastric cancer diagnosis and disease evaluation.

PMID- 8742648
TI  - Aortic pressure pain: clinical significance. Any relationship to the irritable
      bowel syndrome?
AB  - Pressure pain over the abdominal aorta is a clinical sign of undetermined
      significance. Ultrasonographic criteria were used to define and further evaluate
      this variety of epigastric tenderness. The incidence of aortic pressure pain,
      aortic characteristics, and gastrointestinal symptoms were scored in 250
      consecutive patients. The incidence was approximately 7%. All the patients with
      aortic pressure pain had gastrointestinal symptoms, with a significantly higher
      mean symptom score. The occurrence of pressure pain was independent of any of the
      examined aortic characteristics, age, or body mass index. We further compared the
      incidence of aortic pressure pain between 25 patients with irritable bowel
      syndrome and 25 patients without apparent functional gastrointestinal disease. It
      was present in approximately 50% of the patients with irritable bowel syndrome.
      We found pressure pain over the abdominal aorta to be associated with significant
      gastrointestinal discomfort. A causal relationship is possible but not proven.
      Aortic pressure pain can be provoked in a significant subgroup of patients with
      the irritable bowel syndrome.

PMID- 8742649
TI  - Patterns of postoperative recurrence in fistulizing and stenotic Crohn's disease.
      a retrospective cohort study of 71 patients.
AB  - To compare the time course of clinical recurrences and reoperations following
      primary resections for fistulization versus fibrostenotic obstruction in ileal
      Crohn's disease, we performed a retrospective cohort study of 71 patients
      undergoing their first resection at The Mount Sinai Hospital between 1961 and
      1984. Among these 71 patients, 35 were classified as fistulizing and 36 as
      fibrostenotic. Follow-up was 93% complete through 1990, with a median follow-up
      of 73 months to reoperation and 105 months to last contact. The fistulizing and
      fibrostenotic patients experienced virtually identical numbers of clinical
      recurrences: 25 from the former group and 24 from the latter. The recurrences
      appeared very slightly earlier among the fistulizing than among the fibrostenotic
      group, but the difference did not approach statistical significance. Only 18
      patients came to reoperation during follow-up: 12 from the fistulizing and 6 from
      the fibrostenotic group. The earliest reoperation in the fistulizing group
      occurred at 14 months and in the fibrostenotic group at 44 months. There was a
      trend for earlier reoperation in the fistulizing group, but the difference was
      not statistically significant. Different clinical patterns of Crohn's disease
      have yet to be correlated with distinctive subclinical biologic markers.

PMID- 8742650
TI  - Increased prostaglandin E2 and leukotriene B4 synthesis in isolated colonic
      mucosal cells in inflammatory bowel disease. a preliminary report.
AB  - The synthesis of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in colonic
      mucosal cells was investigated in 7 patients and 10 controls. Biopsies obtained
      from the descending colon were isolated biochemically by a special technique and
      the suspension of isolated colonic cells was incubated during 45 min. Compared
      with healthy subjects, patients with an inflammatory bowel disease showed a
      significantly increased PGE2 production. The LTB4 synthesis was enhanced as well,
      but this change was not statistical. We conclude that PGE2 is the dominant
      eicosanoid during less severe inflammatory bowel disease. Age and gender did not
      influence PGE2 or LTB4 synthesis.

PMID- 8742651
TI  - Hepatitis C: a disease with a wide morphological spectrum?
AB  - We describe the pathological findings of 50 biopsies of Mexican (Mestizo, or
      mixed race, usually Indian and white heritage) patients with hepatitis C
      infection confirmed by a second generation test. Although half of the patients
      were asymptomatic, the histological examination revealed advanced stages of
      disease. Chronic active hepatitis was found in 26 cases, cirrhosis in 23, and
      acute hepatitis in one case. Common histological changes included steatosis,
      lymphoid aggregates, and apoptotic bodies, whereas indisputable bile duct damage
      was observed in only four cases. Comparison with other series in which different
      types of populations were analyzed revealed a wide morphological spectrum with
      respect to some histological changes and the type of hepatitis reported. The
      apparently contradictory results found in the literature indicate the need to
      apply universal histological criteria in biopsies of patients with hepatitis C.

PMID- 8742653
TI  - Adenocarcinoma of the esophagus complicating Cornelia de Lange syndrome.
AB  - Complicated gastroesophageal reflux disease may be seen in a variety of
      congenital developmental syndromes, but progression of Barrett's metaplasia to
      adenocarcinoma is rare. We report the first case of esophageal adenocarcinoma in
      a young adult with Cornelia de Lange syndrome who had long-standing
      gastroesophageal reflux disease. We review the literature concerning Barrett's
      metaplasia in children and make recommendations for surveillance.

PMID- 8742652
TI  - Ischemic hepatitis in cirrhosis. clinical features and prognostic implications.
AB  - To characterize liver dysfunction in patients with cirrhosis after variceal
      bleeding, we analyzed 50 cirrhotic patients who had bleeding esophageal varices
      with or without shock. Increases in serum total bilirubin levels by 1.5 times
      were observed within 24 h in 11 of 12 patients with shock who died > 4 days after
      hemorrhage but in only one of eight patients with shock who survived (p < 0.01).
      Increases in serum aspartate aminotransferase and alanine aminotransferase by 2.5
      times were observed in six patients in the former group but in none of the latter
      (p < 0.05). In postmortem livers, hepatocellular degeneration with minimal
      inflammatory cell infiltration was observed. Ischemic hepatitis is frequently
      noted in cirrhotic patients with ruptured esophageal varices. Patients with
      increases in the serum level of total bilirubin and/or aminotransferases within
      24 h from onset of hemorrhage should be carefully treated even if hemorrhage is
      controlled.

PMID- 8742654
TI  - Collagenous gastritis associated with lymphocytic colitis.
AB  - Collagenous sprue and collagenous colitis are two well-recognized idiopathic
      enteritides whose defining histologic attribute is fibrous thickening of the
      subepithelial basement membrane. Analogous changes in gastric mucosa seem to be
      quite rare. The term "collagenous gastritis" was recently applied for the first
      time to an isolated case of refractory gastritis in which distinctive
      subepithelial gastric fibrosis was noted. We report an additional case of this
      entity in a 35-year-old woman with refractory dyspepsia. In contrast to the
      earlier case of collagenous gastritis, our patient also had lymphocytic colitis,
      a type of colitis associated with watery diarrhea. Collagenous gastritis appears
      to be a distinct clinicopathologic entity, the histologic changes of which should
      be sought in patients with unexplained dyspepsia. Increased awareness of this
      condition and its possible clinical correlates may provide clues to its etiology
      and pathogenesis.

PMID- 8742655
TI  - Upper-gastrointestinal bleeding from angiodysplasia of the minor papilla.
AB  - Angiodysplasia is an often unrecognized cause of upper-gastrointestinal bleeding,
      most commonly found in the antrum of the stomach but also in the duodenum and
      rarely in the esophagus. Small-intestinal angiodysplasia is the source of
      gastrointestinal bleeding of obscure origin in 30-40% of cases. The diagnosis is
      usually made by esophagogastroduodenoscopy, push enteroscopy, or selective
      angiography. We report the first case of angiodysplasia of the minor papilla
      diagnosed by side-viewing duodenoscopy.

PMID- 8742656
TI  - Antiphospholipid syndrome manifested by ischemic stroke in a patient with Crohn's
      disease.
AB  - Cerebrovascular accidents are rare but well documented in patients with Crohn's
      disease. Up to 10% of hypercoagulable state manifestations reported in
      association with inflammatory bowel disease are ischemic strokes. However, no
      clear mediating factor has thus far been suggested. A 44-year-old woman with
      Crohn's disease for 25 years developed a left temporal stroke associated with
      anticardiolipin antibody and lupus anticoagulant suggesting antiphospholipid
      syndrome. A thorough evaluation did not reveal any other risk factor for ischemic
      stroke. No possible sources of emboli were found in the carotids and heart, and
      no deficiencies of protein C and activated protein C, protein S, and anti
      thrombin III leading to hypercoagulable state were present. There may be a
      possible association between antiphospholipid syndrome and hypercoagulable state
      in Crohn's disease.

PMID- 8742657
TI  - Ganciclovir treatment of active hepatitis B virus infection in a heart transplant
      patient.
AB  - Hepatitis B virus (HBV) infection in patients who undergo organ transplantation
      is a serious illness, associated with progressive and often fatal liver disease.
      Attempts at eradication of infection with antiviral agents, such as interferon
      and adenine arabinoside, have produced disappointing results. Similarly,
      prevention of HBV reinfection with the use of passive immunization with hepatitis
      B immunoglobulin or a combination of active and passive immunization have not
      been uniformly successful. We report the successful use of ganciclovir, a
      synthetic analogue of 2-deoxyguanosine, in a heart transplant patient with active
      HBV infection. The patient developed decompensated liver disease with ascites,
      edema, and marked derangement of liver tests despite drastic reduction in
      immunosuppressive therapy. Ganciclovir therapy was administered intravenously,
      and the patient showed remarkable improvement with clinical recovery and
      normalization of the liver tests. Moreover, the serum HBV DNA and hepatitis B e
      antigen became undetectable. Ganciclovir was a safe and effective treatment of
      HBV infection in this transplant patient.

PMID- 8742658
TI  - Mesenteric fibromatosis in Crohn's disease.
AB  - We have seen two patients with Crohn's disease and mesenteric fibromatosis, the
      least common form of desmoid tumor. Although both gastrointestinal and
      nongastrointestinal tumors are relatively common in Crohn's disease, this type of
      tumor has not been seen in > 1,650 patients operated on for this condition. As
      the only common factor in the two male patients discussed in this article was
      previous intestinal resections, surgical trauma may be a predisposing factor in
      the occurrence of these desmoid tumors. We will continue to search for other
      examples in patients with Crohn's disease.

PMID- 8742659
TI  - A case of alpha-fetoprotein-producing gastric cancer showing an exogastric growth
      pattern.
AB  - A case of alpha-fetoprotein (AFP)-producing gastric cancer, which showed a huge
      abdominal mass due to an exogastric growth, is here described. A 69-year-old
      Japanese woman with a huge abdominal mass, measuring 22 x 15 cm in size, had a
      serum AFP level that was exceptionally high (155 x 10(3) ng/ml). CT, barium meal
      studies, and gastrointestinal fiberoscopy revealed a gastric tumor with an
      exogastric growth pattern. The patient underwent a partial gastrectomy. The
      histological examination revealed that the tumor consisted of anaplastic
      carcinoma with positive staining for AFP. Although no liver metastasis was
      observed at operation, she died of multiple liver metastases 8 weeks after the
      operation. A gastric cancer that shows both AFP production and an exogastric
      growth pattern is quite rare and may be virulent.

PMID- 8742660
TI  - XXI meeting of the European Duodenal Club. Antwerp, Belgium: October 28-30, 1995.

PMID- 8742661
TI  - Gastric mucosal calcinosis in a patient with dyspepsia.

PMID- 8742662
TI  - Early detection of strongyloidiasis using endoscopic duodenal biopsy: report of a
      case.

PMID- 8742663
TI  - Symptomatic response to omeprazole in inflammatory bowel disease.

PMID- 8742664
TI  - Leukopenia and thrombocytopenia as adverse effects of treatment with 5
      aminosalicylic suppositories.

PMID- 8742665
TI  - Incidence of diarrhea and Clostridium difficile toxin in stools from hospitalized
      patients receiving clindamycin, beta-lactams, or nonantibiotic medications.

PMID- 8742666
TI  - Possible granulomatous hepatitis after dicloxacillin therapy.

PMID- 8742667
TI  - Managed care, or Scope hits the Sphinx. Further thoughts.

PMID- 8742668
TI  - Neurobiology of psychosocial factors in peptic ulcer.

PMID- 8742669
TI  - Invisible victims: battered women in psychiatric and medical emergency rooms.
AB  - Violence against women by their male partners is widespread and infrequently
      identified as a causal factor in multiple physical and psychological problems of
      female patients in medical and psychiatric settings. Three main
      countertransferences that interfere with accurate identification of battered
      women are described: (1) counter- identification, (2)countertransference rage,
      and (3) countertransference helplessness. Battering men and battered women are
      found in all levels of society, although younger, lower income, less-educated men
      who have observed parental violence in their own home are at higher risk of
      abusing their spouses. Additionally, antisocial personality disorder, depression,
      and/or alcohol and drug abuse increase the risk of male violence in the home.
      Contrary to popular belief, the husband-to-wife violence is usually motivated by
      his need to control her rather than a result of his loss of control. Battered
      women show no consistent prebattering risk markers, except for a history of
      parental violence in their family of origin. Violence against women by their male
      partners is a serious public health problem that has not been adequately
      addressed by the medical and psychiatric professions. Myths and clinical
      realities of battered women are described and detailed recommendations for
      clinical inquiry and evaluation of level of danger are given.

PMID- 8742670
TI  - Women and trauma: a contemporary psychodynamic approach to traumatization for
      patients in the OB/GYN psychological consultation clinic.
AB  - Many patients referred to an OB/GYN psychological consultation clinic were found
      to be suffering from the emotional effects of early traumatization. Obstetrical
      and gynecological conditions possess a unique power to reactivate psychological
      damage originally engendered by trauma. A contemporary psychodynamic model of
      trauma and its sequelae proved useful in intervening psychologically and in
      helping these patients and their physicians to improve the management of their
      medical conditions. This model represents an effort to integrate: (1) Herman's
      (1992) conception of complex posttraumatic stress disorder, (2) character
      development in individuals with early traumatic experiences, and (3) Weiss and
      Sampson's (1986) formulations regarding "unconscious pathogenic beliefs"-the
      dread that one's worst unconscious fears will be confirmed. Two clinical cases-a
      pregnant teenager and a woman with hyperemesis gravidarum (excessive and
      persistent vomiting in pregnancy)-illustrate the frequent emergence of
      transference-countertransference dynamics centered around "blaming the victim" in
      work with these patients. Suggestions for therapeutic interventions in short-term
      consultation with these patients are articulated.

PMID- 8742671
TI  - Axis I and II comorbidity and childhood trauma history in chemical dependency.
AB  - The authors replicated and extended two former studies on Axis I and II
      comorbidity and childhood trauma histories in 106 patients admitted to a chemical
      dependency treatment unit. Sixty-nine subjects reported a history of physical
      and/or sexual abuse during childhood and 26.4% met criteria for posttraumaic
      stress disorder. Patients who reported a history of childhood abuse showed more
      symptoms of depression, dissociation, and borderline personality disorder than
      those who denied childhood trauma. Dissociative disorders, mood and anxiety
      disorders, personality disorders, and histories of childhood trauma appear to be
      common in chemical dependency subjects, and should be inquired about routinely.

PMID- 8742672
TI  - Helen Bramson: treatment after sexual abuse by a mental health practitioner.
AB  - Patients who have had sexual contact or sexualized relationships with previous
      therapists present a unique set of subsequent treatment challenges. From the
      patient's perspective, the breach of trust experienced in the previous therapy
      has likely made the formation of a new therapeutic alliance both threatening and
      compelling. It is also likely that whatever caused the patient to enter therapy
      in the first place has never been adequately treated.

PMID- 8742673
TI  - Excessive crying in infants with regulatory disorders.
AB  - The authors point out a correlation between regulatory disorders in infants and
      the problem of excessive crying. The literature describes other behavioral
      problems involving excessive crying in very young children, but with little
      emphasis on this association. The recognition and diagnosis of regulatory
      disorders in infants who cry excessively can help practitioners design
      appropriate treatment interventions. Understanding these conditions can also help
      parents tailor their caretaking style, so that they provide appropriate soothing
      and stimulation to their child. In so doing, they will be better able to develop
      and preserve a satisfactory parent-child relationship, as well as to maintain
      their own sense of competence and self-esteem as parents.

PMID- 8742674
TI  - Success inhibitions in neurotic and character-disordered patients.
AB  - Freud's initial understanding of "wreckage by success" involved oedipal
      conflicts. Since that time, preoedipal issues have also been identified as
      underlying success inhibitions. Work inhibitions in character-disordered patients
      may be ignored because of our general understanding of how pathological ego and
      superego functioning interferes in work, as in all areas. However, after
      significant psychotherapeutic work has been done, the author has often found that
      such patients have remaining work problems that should be viewed as inhibitions
      rather than deficits. Separation fears often underlie success inhibitions in more
      disturbed patients. Careful understanding of work inhibitions in more disturbed
      patients is crucial, because in many such patients, more freeing of functioning
      is possible in the work sphere than in intimate relationships. Two cases are
      presented to illustrate oedipal-level and preoedipal conflicts related to
      success.

PMID- 8742675
TI  - Placebo effects and antidepressant medication: implications for research and
      clinical care.
AB  - Research on the effectiveness of psychiatric treatments, both psychological and
      somatic, must control for nonspecific effects that may bias the results. Studies
      of antidepressant medications are complicated by the nonspecific effects of
      prescribed medications and patients' expectations of the medication, that is,
      placebo effects. This paper will review aspects of the placebo effect as it
      relates to research and clinical care.

PMID- 8742676
TI  - Object representations, interpersonal behavior, and their relationship to the
      dream reports of latency-age girls.
AB  - The application of object representation scales to children's dream material
      offers a means of looking at the relationship of object representations to the
      psychological, interpersonal, and psychopathological variables of the child
      dreamer. The authors reviewed the Object Representation Scale for Dreams (ORSD)
      and determined that it differentiated a clinically pathological group of children
      from a nonpathological group when applied to recalled-dream reports. The
      nonpathological group obtained higher object representational level scores.

PMID- 8742677
TI  - Migraine headache in a prepaid health plan: ascertainment, demographics,
      physiological, and behavioral factors.
AB  - BACKGROUND: Migraine is a prevalent disorder whose relationship to other
      conditions remains poorly understood. METHODS: Associations between migraine and
      physiological, behavioral, and demographic characteristics were assessed in a
      retrospective cohort study of 79,588 enrollees in a large prepaid health
      maintenance organization who underwent a multiphasic preventive health checkup in
      1971-1973. RESULTS: Migraine was found to be inversely associated with age and
      education and strongly associated with the female sex. The likelihood of migraine
      was significantly higher among blacks, smokers, those who drink more than six
      cups of coffee per day, those with Raynaud's syndrome, and those with a family
      history of migraine. The magnitude of associations between migraine and other
      factors was, in general, reduced among those with a self-reported physician
      diagnosis of migraine compared to those whose migraine status was defined on the
      basis of reported symptoms. CONCLUSIONS: Migraine prevalence was found to be
      higher in blacks and other unspecified minorities than in the white population.
      The magnitude of the associations between migraine and behavioral risk factors
      was strongly influenced by the method of migraine ascertainment. The inverse
      association with level of education suggests that social causation or drift may
      have been operating in this disease in the early 1970s, 15 to 20 years earlier
      than recent population-based studies would suggest. Further research is needed to
      fully appreciate the spectrum of disease and behaviors associated with migraine.

PMID- 8742678
TI  - Psychosocial functioning in schoolchildren with recurrent headaches.
AB  - The psychosocial functioning of 113 schoolchildren (8 to 15 years old) reporting
      headaches at least once a month was compared to a group of headache-free control
      subjects matched for sex and age. Thirteen percent of the headache sufferers had
      migraine headaches, 28% had episodic tension-type headaches, 30% had chronic
      tension-type headaches, and 29% had migraine coexisting with tension-type
      headaches. Overall, the headache sufferers experienced more somatic complaints,
      stress, and psychological symptoms, in addition to being absent from school (due
      to illness), more often and reported fewer caring persons as compared to headache
      free controls. Although few differences between the four headache groups emerged
      in the children's psychosocial functioning levels, children with migraine
      coexisting with tension-type headaches had significantly more frequent somatic
      complaints than those having episodic tension-type headaches. In addition,
      children with migraine or migraine coexisting with tension-type headaches were
      more often absent from school than those having tension-type headaches only. A
      significant but weak relationship between children's headache severity and their
      somatic complaints was noted.

PMID- 8742679
TI  - Magnetic resonance imaging for recurrent headache in childhood and adolescence.
AB  - We investigated 429 consecutive patients, aged 5 to 18 (mean: 11.0 +/- 3.1)
      years, diagnosed with migraine or tension-type headache. The patients underwent
      either MRI or exclusively clinical follow-up examinations. Magnetic resonance
      imaging revealed normal findings in 82.3% and structural changes in 17.7%.
      However, the vast majority of these changes had minimal or no pathological
      relevance, and a causal relationship to the patient's headache could not be
      proven in any case. In the non-MRI group, clinical follow-up examinations
      confirmed the initial diagnosis in all patients and MRI was not required in any
      of these subjects. In conclusion, our study shows a poor relation between
      recurrent headache fulfilling the criteria of migraine and tension-type headache
      and structural changes incidentally detected by MRI. In addition, it suggests
      that clinical follow-up examinations are reliable. Accordingly, MRI is not
      required for routine examination of recurrent headache in children and
      adolescents, but it should be performed in patients with abnormal neurological
      findings, atypical headache pattern, or significant change of preexisting
      headache.

PMID- 8742680
TI  - beta-endorphin in plasma and monocytes in juvenile headache.
AB  - Interictal serum levels of serotonin and plasma and mononuclear cell
      concentrations of beta-endorphin were measured in 20 juvenile patients (13
      suffering from migraine without aura and 7 from episodic tension-type headache)
      before and after 3 months of L-5-hydroxytryptophan treatment (5 mg/kg/day) and
      compared with a control group of 17 headache-free healthy subjects. While no
      significant differences in serum serotonin levels emerged between the three
      groups (migraine 104.6 +/- 26 micrograms/L, tension-type headache 90.7 +/- 26.2
      micrograms/L, controls 96 +/- 32.9 micrograms/L), significantly lower plasma and
      mononuclear cell concentrations of beta-endorphin were found in both patient
      groups by comparison with the healthy controls (beta-endorphin in plasma:
      migraine sufferers 16.2 +/- 4.2 pmol/L [P < 0.05], tension-type headache subjects
      14.5 +/- 1.7 pmol/L [P < 0.001] vs controls 21.3 +/- 4.6 pmol/L and respectively,
      beta-endorphin in mononuclear cells: migraine sufferers 110.5 +/- 16.4 pmol/10(6)
      GB/L [P < 0.001], tension-type headache subjects 142.3 +/- 22.7 pmol/10(6) GB/L
      [P < 0.001] vs controls 359.3 +/- 31.6 pmol/10(6) GB/L). No differences emerged
      between the two clinical forms of headache for the plasma and mononuclear cell
      concentrations of beta-endorphin. After L-5-hydroxytryptophan treatment, serum
      serotonin and both plasma and mononuclear cell beta-endorphin levels tended to be
      higher, though not significantly so, than prior to treatment, and the clinical
      score (frequency x intensity of headache attacks) was significantly lower in both
      headache groups than at the baseline. This study supports the theory that opiate
      analgesic system function is abnormally low in juvenile primary headache as in
      adults, and confirms that administering serotoninergic precursor drugs increases
      beta-endorphin, even in the peripheral blood, and may favorably affect clinical
      symptoms.

PMID- 8742681
TI  - Platelet responsiveness in migrainous children during headache-free period.
AB  - Results of this study confirm the link between migraine and alterations of
      platelet responsiveness. Our data suggest that in migraineurs the perturbated
      platelet microviscosity, analyzed by means of fluorescence polarization, appears
      responsible for the decrease of stimulation-induced influx of external calcium
      through the platelet membrane. These findings suggest that platelet membrane
      microviscosity may be considered as a more significant platelet marker of
      migraine rather than the well-known and nonspecific phenomenon of platelet
      hyperaggregation, evaluated by time-transmittance variations induced by adenosine
      diphosphate and collagen.

PMID- 8742682
TI  - Salivary substance P, 5-hydroxytryptamine, and gamma-aminobutyric acid levels in
      migraine and tension-type headache.
AB  - Substance P, 5-hydroxytryptamine, and gamma-aminobutyric acid levels in saliva
      were measured in 55 patients with migraine during headache attacks (15 men and 40
      women, average age 37.6 years), 36 patients with migraine in interictal periods
      (8 men and 28 women, average age 43.9 years), 48 patients with tension-type
      headache during headache attacks (18 men and 30 women, average age 47.3 years),
      and 25 patients with tension-type headache in interictal periods (10 men and 15
      women, average age 48.6 years). Forty-three normal healthy volunteers composed
      the control group (17 men and 26 women, average age 32.7 years). Substance P
      levels in saliva were determined using competitive enzyme-linked immunosorbent
      assay, and were 26.9 +/- 45.1 pmol/mL in the patients with migraine during
      headache attacks, 30.0 +/- 59.7 pmol/mL in the patients with migraine in
      interictal periods, 243.5 +/- 1137 pmol/mL in the patients with tension-type
      headache during headache attacks, 101.3 +/- 364 pmol/mL in the patients with
      tension-type headache in interictal periods, and 21.2 +/- 17.4 pmol/mL in the
      healthy controls. 5-hydroxytryptamine levels in saliva were determined using
      reversed-phase high-performance liquid chromatography with electrochemical
      detection, and were 895 +/- 1075 ng/mL in the patients with migraine during
      headache attacks, 758 +/- 1375 ng/mL in the patients with migraine in interictal
      periods, 1646 +/- 1945 ng/mL in the patients with tension-type headache during
      active headache periods, 1167 +/- 1495 ng/mL in the patients with tension-type in
      headache-free periods, and 450 +/- 405 ng/mL in the healthy controls. Gamma
      aminobutyric acid levels in saliva were determined using high-performance liquid
      chromatography with precolumn ortho-phthalaldehyde fluorescence detection. Gamma
      aminobutyric acid levels in saliva were 36.8 +/- 49.8 pmol/mL in the patients
      with migraine during headache attacks, 17.9 +/- 25.2 pmol/mL in the patients with
      migraine in interictal periods, 16.0 +/- 18.3 pmol/mL in the patients with
      tension-type headache during active headache periods, 14.1 +/- 6.8 pmol/mL in the
      patients with tension-type headache in headache-free periods, and 21.6 +/- 22.7
      pmol/mL in the healthy controls. The salivary substance P and 5-hydroxytryptamine
      levels in the patients with tension-type headache during active headache periods
      were significantly higher than those in healthy controls. In contrast, we found
      no significant differences between the salivary gamma-aminobutyric acid levels in
      the patients with tension-type headache and healthy controls. The high levels of
      salivary substance P and 5-hydroxytryptamine in tension-type headache patients
      during headache periods might reflect release of substance P from the pain
      sensory system. Saliva could represent a fluid particularly suitable to the study
      of neuropeptide release under specific conditions such as migraine and tension
      type headache.

PMID- 8742683
TI  - Analgesic use in cluster headache.
AB  - Cluster headache is a brutal affliction characterized by excruciating pain with
      relatively brief, but frequent attacks. Because of the short duration of the
      attacks and the tremendous intensity of pain, symptomatic analgesics are often
      not effective. However, inhalation oxygen, while being cumbersome, is reported to
      be effective in the majority of sufferers. To assess the practical effectiveness
      and use of analgesics and/or oxygen, a review of 60 cluster patients was
      conducted. At initial evaluation, 48 patients had accepted oral analgesics and 51
      patients accepted inhalation oxygen for breakthrough headaches. After acceptable
      prophylactic treatment was established, 65% of patients who accepted analgesics
      continued their use, although most reported only minimal relief. Only 31% of
      patients who accepted oxygen continued its use, in spite of the fact that most
      sufferers reported significant relief. From this brief study, it appears that
      cluster headache patients prefer to use analgesics for reasons that are not
      solely for relief of pain, and that patients decline the use of oxygen for
      reasons other than lack of effectiveness.

PMID- 8742684
TI  - SUNCT syndrome. Atypical temporal patterns.
AB  - New clinical features of the SUNCT syndrome are described in a series of 3 men
      (mean age of 65 years, range 56 to 80). The mean age at the onset of symptoms was
      55 years (range 39 to 77). Although in all patients the great majority of attacks
      were typical, on a few occasions unusual features of the painful attacks were
      either reported or witnessed by the investigators. We have classified these
      clinical phenomena as (1) low-grade background pain or discomfort, and (2)
      relatively long-lasting attacks. Neither neurological examination nor
      neuroimaging studies revealed structural lesions as responsible for the atypical
      features. The fact that these atypical attacks occurred in the usual symptomatic
      area and were accompanied by the usual ipsilateral autonomic signs, suggests that
      they are an integral part of the clinical picture of SUNCT. The possibility that
      another, concurrent headache was responsible for the unusual attacks is
      considered unlikely. These clinical phenomena should, accordingly, provisionally
      be considered as additional but rare clinical features of the SUNCT syndrome.

PMID- 8742685
TI  - EEG and topographic frequency analysis in migraine attack before and after
      sumatriptan infusion.
AB  - Electroencephalographic changes occurring in patients with migraine have received
      much attention. Although in migraineurs a number of studies have been done after
      nitroglycerin-induced attacks, there is no reported EEG study before and after
      nitroglycerin-induced sumatriptan-treated attacks. We, therefore, studied the EEG
      topographic frequency analysis in 19 symptom-free, otherwise healthy, unmedicated
      patients with common migraine and in 19 age- and sex-matched controls before
      nitroglycerin, at the time of maximum pain, and 30 minutes after sumatriptan.
      During headache attacks, an increase of slow rhythmic activity of the theta and
      delta range and a decrease of activity in the alpha and beta range were observed.
      These abnormalities disappeared 30 minutes after a sumatriptan injection. This
      suggests that common migraine is associated with disturbances of cortical
      electrogenesis and may provide insight into the causes of migraine and aid in the
      development of effective therapies.

PMID- 8742686
TI  - Behcet's disease: presentation with sagittal sinus thrombosis diagnosed
      noninvasively.
AB  - The standard evaluation of patients with intracranial hypertension frequently
      does not reveal a discrete pathophysiologic process, leading in these cases to
      classification of the syndrome as "benign." We present a 35-year-old woman with a
      recent diagnosis of pseudotumor cerebri who presented with headache, emesis, and
      blurring of vision. Her symptoms were progressive despite two lumbar punctures
      that revealed normal cerebrospinal fluid under high pressure. Contrast and
      noncontrast CT scans were normal; both the cerebrospinal fluid and CT
      neuroimaging were thus consistent with benign intracranial hypertension. An MRI,
      however, supported the presence of sagittal sinus thrombosis, a finding which was
      confirmed by MR venography. Further workup for an underlying cause of sinus
      thrombosis disclosed symptoms and signs fulfilling the diagnostic criteria for
      Behcet's disease. Cerebral venous (or sinus) thrombosis should be considered in
      the differential diagnosis of intracranial hypertension. Behcet's disease, while
      extremely rare, should be considered as a potential cause of cerebral venous
      thrombosis. Magnetic resonance venography can serve as a useful diagnostic study
      in situations where confirmation or exclusion of sinus thrombosis is required.

PMID- 8742687
TI  - Severe barbiturate withdrawal syndrome in migrainous patients.
AB  - Three patients who presented with grand mal seizures and an associated behavioral
      disorder were recognized as suffering from a severe butalbital withdrawal
      syndrome. All were migraineurs who had become dependent on barbiturates. We
      propose that the occurrence of seizures, psychotic behavior, or a recent
      personality change should be considered clues to possible barbiturate abuse in
      patients with migraine.

PMID- 8742689
TI  - Rate of aerobic metabolism and superoxide production rate potential in the
      nematode Caenorhabditis elegans.
AB  - We have monitored oxygen consumption as a measure of the rate of aerobic
      metabolism during the lifetime of Caenorhabditis elegans. We have also developed
      a chemiluminescent technique which measures exogenous NADPH-stimulated superoxide
      anion production by freeze-thawed worms. In this assay light production depends
      on the combined activities of all of the enzymes involved in superoxide
      production, both directly and indirectly, thus reflecting their activity levels
      immediately prior to freeze fixation. We have designated this parameter the
      superoxide production rate potential. The superoxide production rate potential is
      controlled by the longevity determining gene age-1 and varies in a life cycle
      dependent fashion. The metabolic rate generally follows these fluctuations, but
      additionally shows specific alterations as a response to environmental factors.
      Metabolic rate and superoxide production rate potential increase by 1.3- and 3
      fold, respectively, in reproducing adults. This increase is not due to the
      contribution of embryonating eggs, however. Culture conditions have a large
      effect on metabolic rate, but not on the superoxide production rate potential.
      The energetic cost of movement, measured as consumed oxygen, is low relative to
      the costs of maintenance and reproduction. Identical superoxide production rate
      potentials are scored in paralyzed and motile worms, as would be expected.

PMID- 8742688
TI  - Erythropoietin stimulates tyrosine phosphorylation and taurine transport in skate
      erythrocytes.
AB  - Taurine, a beta amino acid, is a primary osmolyte in nucleated skate erythrocytes
      and is involved in the regulation of cell volume. Growth factors may be involved
      in the regulation of cell volume which occurs during cell division.
      Erythropoietin (EPO) is the primary growth factor controlling erythropoiesis. To
      investigate its mechanism of action, we used nucleated skate erythrocytes. EPO
      stimulates Na(+)-independent uptake of taurine in a concentration-dependent
      manner. The uptake was inhibited by the tyrosine kinase inhibitor genistein.
      Concomitantly, EPO stimulates tyrosine phosphorylation of a number of proteins,
      particularly ones of molecular masses 145, 120, 100, 80, 65, and 35 kDa. Using
      specific antibodies, the 145 kDa protein is identified as phospholipase C gamma-1
      (PLC gamma-1) and the 100 kDa protein as the skate homolog of the anion exchanger
      band 3. Since PLC gamma-1 is activated, turnover of membrane lipids was
      determined. EPO increased 1,2-diacylglycerol formation from phosphatidylinositols
      (phosphatidylinositol-4-monophosphate and 4,5-biphosphate) during an early phase
      and later preferentially from phosphatidylcholine. The early hydrolysis of
      phosphoinositides was confirmed measuring generation of inositol-1,4,5
      trisphosphate, demonstrating an activation of PLC gamma-1 activity. To determine
      if phospholipase D (PLD) stimulation also occurred, ethanol was included in the
      reactions. Phosphatidylethanol, synthesized by PLD-mediated
      transphosphatidylation, appeared at times longer than 5 min, suggesting delayed
      activation of PLD. These results demonstrate that EPO, via simulation of tyrosine
      phosphorylation, stimulates taurine transport in skate erythrocytes.

PMID- 8742690
TI  - Regulation of preimplantation development of mouse embryos: effects of inhibition
      of myosin light-chain kinase, a Ca2+/calmodulin-dependent enzyme.
AB  - We have examined the effects of ML-9 and wortmannin, which are, respectively,
      specific reversible and irreversible inhibitors of myosin light-chain kinase, a
      Ca2+/calmodulin-dependent enzyme, on preimplantation development of the mouse in
      an attempt to establish a regulatory role for this enzyme in preimplantation
      development. When late two-cell stage embryos were treated continuously with ML-9
      or wortmannin at a concentration of 0, 1, 5, 10, or 15 microM, compaction and
      formation of the blastocyst were inhibited in a dose-dependent manner. Stage
      specific treatment with ML-9 at 25 microM induced stage-specific responses of
      embryos after the eight-cell stage during the processes of compaction and
      cavitation. These morphological responses included aborted compaction,
      decompaction of compacted embryos, and the inability of embryos to form a cavity.
      These morphological effects were reversible, but, since cell proliferation was
      inhibited, the "recovered" embryos were small. Counting of cells on day 4 of
      culture, in both continuously treated and stage-specifically treated embryos,
      showed that the effect of ML-9 on cell proliferation was also dose-dependent.
      Wortmannin also had stage-specific effects at 15 microM, but these effects were
      irreversible and were more deleterious than those of ML-9. With neither inhibitor
      was there any apparent effect at the two-cell or the four-cell stage, although
      wortmannin inhibited cell division when applied stage-specifically at the four
      cell stage. These results indicate that myosin light-chain kinase may be an
      important enzyme in the first steps of differentiation and in the maintenance of
      the differentiated state during preimplantation development of the mouse.

PMID- 8742691
TI  - Effects of cell-cycle-arrest agents on cleavage and development of mouse embryos.
AB  - In mammals, there are no reliable methods for synchronizing cell division of
      early embryos without reducing their ability to develop into blastocysts and
      fetuses. The present study was undertaken to examine the in vitro inhibition of
      cell division of four-cell mouse embryos by cell cycle arrest agents. The
      reversibility of the agents was also tested by examining the developmental
      ability of treated embryos. Four-cell mouse embryos obtained at 54 hr post-human
      chorionic gonadotrophin (post-hCG) were cultured for 4, 8, 12, or 16 hr in media
      supplemented with either nocodazole, an inhibitor of tubulin polymerization, 6
      dimethylaminopurine (6-DMAP), an inhibitor of maturation promoting factor (MPF)
      activation, or aphidicolin, a specific inhibitor of DNA polymerase alpha.
      Reversibility and toxicity of these agents were both dose and time dependent. For
      all three agents, prolonging cleavage arrest for 8 or 16 hr (at the effective
      concentrations) caused embryo lethality. Although nocodazole treatment was least
      cytotoxic, 6-DMAP and aphidicolin concentrations which induce cleavage arrest
      were detrimental to development beyond the blastocyst stage. The results of this
      study show that the development of embryos treated with these three cell-cycle
      arrest agents is dose and incubation time dependent. Toxic effects beyond the
      blastocyst stage could only be minimized for nocodazole by reducing the exposure
      time of treatment and concentration of the mitotic inhibitor. However, these
      results render doubt on the usefulness of 6-DMAP and aphidicolin for
      synchronization studies leading to embryo transfer procedures.

PMID- 8742692
TI  - Nuclear internalization of foreign DNA by zebrafish spermatozoa and its
      enhancement by electroporation.
AB  - Mature sperm cells of zebrafish (Danio rerio) incubated with foreign DNA have the
      capacity to take up foreign DNA. Such uptake can be enhanced by electroporation.
      Mature spermatozoa of zebrafish were incubated and electroporated in the presence
      of either radiolabeled or unlabeled plasmid DNA at voltages of 500 or 1,000 or
      1,500 V/cm. From the percentage of radiolabeled plasmids retained on the
      spermatozoa, some sperm showed an ability to spontaneously take up the plasmid
      DNA, and the ability was enhanced one- to twofold by electroporation.
      Fertilization of mature eggs with the treated sperm resulted in transmission of
      the plasmid DNA to the resulting offspring. Frequency of transgenic individuals,
      as monitored by polymerase chain reaction, increased marginally, more than
      doubled and nearly doubled in 500 V/cm, 1,000 V/cm, and 1,500 V/cm electroporated
      groups, respectively, when compared to the non-electroporated group. These
      results indirectly implied that electroporation enhanced the capacity of
      spermatozoa to take up plasmid DNA. The increased field strength, however, had a
      deleterious effect on the motility of the sperm, causing clumping of sperms at
      high voltages. Light microscopic autoradiography of treated spermatozoa was able
      to show that the plasmid DNA was associated with the majority of sperm but was
      unable to differentiate whether it was present inside the nucleus or not.
      Ultrastructural in situ hybridization on thin sections of zebrafish spermatozoa,
      however, was able to show that the exogenous DNA was internalized into the
      nucleus and that electroporation enhanced this internalization. The results
      provide direct evidence for nuclear internalization of foreign DNA by non
      mammalian sperm as in mammalian sperm.

PMID- 8742693
TI  - Ovotestis variability in young and adult females of the mole Talpa occidentalis
      (insectivora, mammalia).
AB  - The age-related evolution and ontogenic origin of the ovotestes in fertile
      females of the Spanish mole (Talpa occidentalis) were studied. Volume of the
      ovotestis and its ovarian and testicular components, size of the epididymis and
      testicular cords, number of ovarian follicles and testicular cords, uterus
      weight, and age index were analyzed statistically in a large sample of young and
      adult individuals of this species. Comparison of means and linear correlation
      analyses were done. Most variables were shown to be age dependent, with a period
      of rapid change during puberty. In adult animals, volume of the ovarian portion
      and uterus weight followed a seasonal cycle of sexual activity. Interindividual
      variability was evident in most of the variables investigated except for the
      number of testicular cords per ovotestis, which remained unchanged throughout the
      animal's life and hence was not inversely correlated with the number of ovarian
      follicles. This finding ruled out an ovary-testis transdifferentiation hypothesis
      for the ontogenic origin of the testicular tissue in the ovotestes of female
      moles. An alternative hypothesis based in the absence of oocytes in a portion of
      the undifferentiated fetal gonad is proposed in accordance with a new general
      model for mammalian sex determination.

PMID- 8742694
TI  - Morphological study of thymus stromal cells (TEL-2 cell) which play a role in the
      elimination of double positive immature thymocytes by phagocytosis.
AB  - BACKGROUND: The process of the selective elimination of immature double positive
      thymocytes, during culture with TEL-2 cells (an epithelial cell line from the
      thymus stroma), is initiated by the contact between thymocytes and TEL-2 cells
      (Nakashima et al. 1990 Eur. J. Immunol., 20: 47-53; Hirata et al. 1991 Anat.
      Rec., 230: 524-530). METHODS: Our approach was to follow the process of thymocyte
      internalization as a sequelae of this interaction with scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), and electron
      microscopic cytochemistry for the hydrolytic enzyme acid phosphatase (Ac Pase).
      RESULTS: With SEM, numerous thymocytes lay underneath the TEL-2 cells. An
      enhanced activity of the TEL-2 cell membrane, consisting of several thin thread
      like projections either with or without an expanded termination, was involved
      with contacting the thymocytes. With TEM, close appositions were noted either at
      adjacent segments of the cellular membrane or between thick plump local
      protrusions of the plasma membrane. Blunt pseudopodia and deep invaginations on
      indented portions of the TEL-2 surface engulfed one or more thymocytes. With Ac
      Pase histochemistry: 1) the incorporation of thymocytes into a phagosome was
      indicated by the Ac Pase negative thymocytes enclosed in a membrane beneath the
      protuberance of a TEL-2 cell surface without fusion to the TEL-2 lysosomes; 2)
      most of these thymocytes were morphologically intact, whereas the rest were
      already damaged, having changes similar to apoptosis; and 3) a few Ac Pase
      positive dense bodies of the TEL-2 cell, mostly with the morphology of secondary
      lysosomes, fused with the thymocyte-enclosing membrane after which the digestion
      of several thymocytes proceeded. CONCLUSIONS: With the prominent activity of the
      plasma membrane involving the initial attachment and subsequent phagocytosis, a
      murine thymic epithelial cell line TEL-2 plays a demonstrating role in the
      mechanism of the elimination of double positive thymocytes.

PMID- 8742695
TI  - Increased cell diameter precedes chondrocyte terminal differentiation, whereas
      cell-matrix attachment complex proteins appear constant.
AB  - BACKGROUND: Chondrocytes in specific areas of chick sterna have different
      developmental fates. Cephalic chondrocytes become hypertrophic and secrete type X
      collagen into the extracellular matrix, whereas middle and caudal chondrocytes
      remain cartilagenous throughout development, continuing to secrete collagen types
      II, IX, and XI. In this report, we ask if the cell size and cytoarchitecture of
      chondrocytes differ in cephalic, middle, and caudal portions of whole sterna
      prior to and during hypertrophy. In addition, what is the distribution of
      integrin subunits and actin associate proteins in differentiating chondrocytes?
      METHODS: Phalloidin was used to stain filamentous actin, and immunohistochemistry
      was used to localize the distribution of collagen molecules, integrin receptor
      subunits, and actin-associated proteins. RESULTS: Chondrocytes stained for
      filamentous actin demonstrated that on day 14 cephalic chondrocytes had a
      significantly larger diameter than middle and caudal chondrocytes. Day 17
      chondrocytes in nonhypertrophic cephalic and middle regions of sterna were
      significantly smaller than hypertrophic chondrocytes and significantly larger
      than caudal chondrocytes. In contrast to day 14 chondrocytes, day 17 chondrocytes
      in the hypertrophic region demonstrated similar diameters at all cartilagenous
      depths. The beta 1 integrin subunit appeared punctate and associated with cell
      membranes, allowing nonpolarized interactions with extracellular matrix
      molecules. The distribution of alpha integrin subunits was similar to the beta 1
      integrin subunit, although alpha integrin subunits also appeared cytoplasmic.
      Actin-associated proteins, vinculin, and alpha-actinin, were associated with F
      actin, but vinculin was more specifically localized to the ends of the actin
      filaments. Focal adhesion kinase was diffusely distributed throughout the
      cytoplasm but also demonstrated areas of colocalization with vinculin. Zyxin and
      paxillin demonstrated a punctate distribution, although paxillin was slightly
      more diffuse. Using immunohistochemical detection, no difference in integrin
      subunit or actin associated protein distribution could be determined between
      chondrocytes and hypertrophic chondrocytes. CONCLUSIONS: The increased
      chondrocyte diameter observed in cephalic regions of sterna on day 14 suggests
      that intracellular changes may precede the specific hypertrophic marker, type X
      collagen, by several days. In addition, the presence of integrin subunits, which
      are known to interact with collagen and cytoskeletal proteins, suggests that
      communication may exist between chondrocytes and their extracellular matrix via
      these receptor molecules.

PMID- 8742696
TI  - Progression of trophoblast into the endometrium during implantation in the
      western spotted skunk.
AB  - BACKGROUND: In mustelid carnivores, several blastocysts become implanted either
      approximately 12 days following fertilization or after a delay of implantation.
      In the western spotted skunk, implantation occurs following a long period of
      delayed implantation and a brief activation stage. Within each implantation
      chamber, a large number of trophoblastic plaques form, and the syncytial
      trophoblast of these plaques adheres to and penetrates into the uterine luminal
      epithelium. The presence of multiple attachment sites was used to analyse the way
      in which trophoblast adheres to, penetrates, and removes uterine epithelium and
      its subsequent association with the subepithelial vascular plexus. METHODS:
      Implantation chambers from 18 western spotted skunks were collected during the
      first week postimplantation and the tissue prepared for light microscopy and
      scanning and transmission electron microscopy. RESULTS: A series of trophoblastic
      plaques, which form a ring peripheral to the embryonic shield, attach to and
      penetrate the uterine epithelium. As new trophoblastic plaques are forming, the
      initial plaques enlarge and spread along the basal lamina of the luminal
      epithelium, and trophoblastic processes project through this basal lamina.
      Subsequently there is a stage of consolidation in which cytotrophoblast increases
      greatly in amount, attachment sites coalesce, and the luminal epithelium is
      eliminated. Syncytial trophoblast intrudes into endometrial gland lumina and
      surrounds subepithelial capillaries. CONCLUSIONS: It is suggested that the
      affinity of syncytial trophoblast for apical junctional complexes of uterine
      epithelial cells facilitates intrusion of syncytial trophoblast between cells,
      possibly guided by the marginal ridges of the uterine cells. The trophoblast
      shows no tendency to adhere to or invade maternal capillaries. This lack of
      adhesion to endothelial cells suggests either a change in adhesive properties of
      trophoblast following epithelial penetration or differences in adhesive
      properties between surface epithelial cells and endothelial cells. Although
      trophoblast differentiation appears to be chronologically regulated, it could be
      responding to maternally derived factors.

PMID- 8742697
TI  - Death and replacement of uterine epithelial cells during oil-induced deciduoma
      development in the mouse.
AB  - BACKGROUND: A decidual cell reaction can be induced in rodent endometrium by an
      intrauterine injection of oil. The epithelial lining is thought to be
      instrumental to transduce intralumenal stimuli for decidualization. One of the
      consequences of oil injection is the death of uterine epithelial cells. No
      information is available on the effect that sustained contact with oil has on the
      epithelium. METHODS: A decidual cell reaction was induced in 4-day pseudopregnant
      mice by injection of 30 microliters of arachis oil into the uterine lumen.
      Samples from the uteri were collected 24, 48, and 72 h after the injection and
      prepared for transmission electron microscopy. RESULTS: Twenty-four hours after
      the oil injection, some of the initial modifications of epithelial cell surfaces
      were very similar to those induced by the contact with the blastocyst during
      normal pregnancy. Uterine epithelial cells internalized injected oil and many
      cells were seen in various stages of degeneration. At 48 h, many epithelial cells
      were detached from the basal lamina. At 72 h, the uterine lining was re
      established by flattened cells. CONCLUSIONS: The contact of oil with the uterine
      epithelium of pseudo pregnant mice induces epithelial cell death in the
      antimesometrial region of the uterine crypt. There is, however, replacement of
      epithelial lining by epithelial cells, which probably migrate from the
      mesometrial region of the crypt. The prolonged presence of oil within the uterine
      lumen seems to induce cycles of epithelial cell death and replacement.

PMID- 8742698
TI  - CRP-ductin: a gene expressed in intestinal crypts and in pancreatic and hepatic
      ducts.
AB  - BACKGROUND: A subtraction screen isolated CRP-ductin (CRP), a gene expressed in
      intestinal crypts. METHODS: DNA sequencing, in situ hybridization,
      immunostaining, Western and Northern blotting were used to characterize murine
      CRP. RESULTS: CRP is restricted to the intestine and its associated glands. In
      the small intestine, CRP mRNA is expressed in crypt cells at all stages of
      differentiation from the stem cells to the terminally differentiating cells of
      the crypt top, but not in the mature cells of the villus. In the colon, CRP mRNA
      is most heavily expressed in the mid-crypt. Expression is also seen in the
      pancreas and pancreatic ducts, and in the epithelium lining larger hepatic ducts,
      but not in the liver parenchyma or stomach. CRP protein is localized to the
      lumenal aspect of crypt cells in the small intestine. In the colon, the protein
      is seen in the lumenal aspect of surface epithelial cells. CRP protein is
      similarly found in the lumenal aspect of epithelial cells lining the pancreatic
      duct system and the larger hepatic ducts. Two cDNA variants, CRP-alpha and CRP
      beta, were cloned from mouse jejunal epithelium. Their 3'-sequence differs in an
      82-bp domain unique to CRP-beta. CONCLUSIONS: The CRP-alpha sequence predicts a
      protein with a short cytoplasmic region, a transmembrane domain, and a large
      extracellular region composed of many repeats (8 scavenger receptor domains, 5
      CUB-domains, 1 ZP-domain, and 6 copies of a previously unreported domain which we
      call the CRP-domain). The structure of the CRP protein suggests a role in ligand
      interaction; possible functions are discussed.

PMID- 8742699
TI  - Intraalveolar bubbles and bubble films. I. formation and development during the
      first 48 hours of extrauterine life in rabbits.
AB  - BACKGROUND: Aeration of mature lungs at birth depends on formation of
      intraalveolar bubbles and bubble films (Scarpelli 1978. Pediatr. Res., 12:1070
      1076). Bubbles establish immediately structural stability and pulmonary gas
      exchange. Given that air spaces are cleared in minutes of fetal liquid (the
      initial substrate for bubble formation), in formation possible beyond this
      period? If so, is this related to early development of pulmonary function and
      structure? METHODS: Mature, spontaneously breathing rabbit pups at 1-10 min and
      1, 3, 8, 24, and 48 h after vaginal birth were anesthetized, trachea was occluded
      at "resting volume" (approximately functional residual capacity), and lungs were
      rapidly exposed to preserve in vivo intrapulmonary status. The entire lung was
      examined by stereomicroscopy. Other determinations included resting volume, lung
      wet weight, volume-pressure curves, histological sections, lung dry weight,
      tissue hydroxyproline (OH-Pro), and lavage phospholipids (PL). Bubble mobility in
      situ was tested. Bubbles were released into bathing liquid by incision of
      peripheral units and monitored over time. RESULTS: Pup activity and gross
      appearance of the lungs, together with septal thinning, secondary septal
      development, clearance of intraluminal liquid, increasing tissue OH-Pro, and PL
      distribution indicated normal postnatal development. Each aerated unit examined
      at resting volume (all lobes, all ages) contained intraalveolar bubbles.
      Transition to free gas exclusively in conducting airways and bubbles/bubble films
      in peripheral gas exchange units occurred within 1 h. Bubbles appeared to be
      exclusively within alveoli at 4 h and thereafter. Bubbles persisted and new
      bubbles were formed during subsequent inflation to maximal volume and deflation
      to atmospheric pressure (P0). Volume of intact lungs at P0 was maintained by the
      counterforce of rigid bubble films against tissue retraction. When bubbles were
      released either at resting volume or at P0, the bubble-free loci became airless.
      Constant size and stability of released bubbles support preferential
      incorporation of surfactants into bubble films and constant "near-zero surface
      tension" (Scarpelli 1978. Pediatr. Res., 12:1070-1076). CONCLUSIONS: We show the
      ubiquitous presence of intraalveolar bubbles and bubble films in vivo throughout
      the first 48 h of postnatal life. Bubble film rigidity sustains aeration and
      prevents collapse, while low surface tension of the films facilitate liquid
      removal from the air spaces. Bubbles in situ are stable and, within apparent
      limits, mobile; after birth they are quickly restricted to the alveolar spaces,
      leaving airways bubble free.

PMID- 8742700
TI  - Similarities and differences in supporting and chromaffin cells in the mammalian
      adrenal medullae: an immunohistochemical study.
AB  - BACKGROUND: The adrenal medulla is a typical paraganglion, having the same origin
      as the sympathetic ganglia, and contains at least two types of parenchymal cells:
      chromaffin cells and supporting cells. We previously reported that the extent of
      cellular association of chromaffin cells with supporting cells was remarkably
      higher in noradrenaline (NA)-than in adrenaline (A)-cell regions in the adrenal
      medullae of the rat and pig. METHODS: Cryostat sections of adrenal medullae of
      nine mammalian species fixed with Zamboni fluid for 24 h were immunostained by
      ABC methods using antisera to S-100 protein and PNMT. RESULTS: The distribution
      patterns of A and NA cells in the adrenal medullae were classified into four
      types. In the chipmunk and rabbit, adrenomedullary chromaffin cells consisted of
      A cells. S-100-immunoreactive cells were present more frequently in NA- than in A
      cell regions in seven species (rat, golden hamster, cat, dog, pig, ox, and
      horse). These cells sent out cytoplasmic processes and formed a network by
      immunoreactive elements among NA cells. The cell-association patterns of S-100
      positive cells with NA cell were classified into three types. In A-cell regions,
      only a few S-100-positive cells were seen in most of the species, although the
      frequency of S-100-labeled cells were exceptionally high in the horse.
      CONCLUSIONS: The close association of supporting cells with NA cells was commonly
      found in the adrenal medulla in many mammalian species, irrespective of the
      proportions and distribution patterns of A cells and NA cells. On the other hand,
      species differences existed in details of the cellular association between
      supporting cells and NA cells.

PMID- 8742701
TI  - Intercellular communication within the rat anterior pituitary gland: VI.
      Development of gap junctions between folliculo-stellate cells under the influence
      of ovariectomy and sex steroids in the female rat.
AB  - BACKGROUND: Farquhar (1957) initially described the folliculo-stellate cells in
      the rat anterior pituitary gland and found them to be located in groups around
      follicles throughout the anterior lobe. Soji and his co-workers have published a
      series of reports concerning cell-to-cell communication in the male rat
      hypophysis involving folliculo-stellate cells as mediated through a gap
      junctional network and recorded a reduction in junctional number following
      castration that was reversed by the administration of testosterone (Soji and
      Herbert, 1990, Anat. Rec., 226:342-346; Soji et al., 1990, Anat. Rec., 226:337
      341). METHODS: Animals were ovariectomized at 10 days of age and separated into
      three groups: (1) intact control, (2) ovariectomized controls, (3) ovariectomized
      and given either estradiol, testosterone, or progesterone. On days 10, 20, 30,
      40, and 45, the pituitary gland from animals in each group was removed and
      processed for ultrastructural examination. RESULTS: Gap junctions in the intact
      control female rats initially appeared between adjacent folliculo-stellate cells
      on day 20. Their numbers linearly increased until the animals reached the age of
      45 days. In contrast, there was a suppression in the number of gap junctions
      present in the ovariectomized groups and a marked enhancement of the junctions in
      each of the three steroid-treated groups. CONCLUSIONS: These findings support the
      observations made in the male rat in which it was found that the development of
      gap junctions in the anterior pituitary gland of the rat is dependent in part on
      the presence of sex steroid hormones.

PMID- 8742702
TI  - Estrogen receptor (ER) and its messenger ribonucleic acid expression in the
      genital tract of female mice exposed neonatally to tamoxifen and
      diethylstilbestrol.
AB  - BACKGROUND: Tamoxifen (Tx) is known as an antiestrogen because of its competitive
      inhibition of estrogen binding to estrogen receptor (ER), and it is used as an
      estrogen antagonist in the human breast. However, Tx is known to have estrogen
      agonist activity in the human fetal reproductive tracts and vaginal epithelium
      and endometrium of postmenopausal women as has been known in the mouse uterus.
      Therefore, we examined estrogenic potency of Tx on the uterus and vagina in
      newborn mice and adult ovariectomized mice. METHODS: Using immunohistochemistry
      and in situ hybridization, we studied changes in expression of ER protein and ER
      mRNA in the uterus and vagina of C57BL/Tw mice exposed neonatally to 100
      micrograms Tx and 0.03-3 micrograms diethylstilbestrol (DES), and changes in
      expression of ER mRNA in the ovariectomized adult mice given injections of 100
      micrograms Tx and 3 micrograms DES. RESULTS: Nuclei of the epithelial and stromal
      cells in the vagina and of the stromal cells in the uterus showed strong ER
      immunostaining on the day of birth (= day 0), whereas nuclei of the epithelial
      cells in the uterus exhibited the ER immunostaining by day 5. In uterine
      epithelial cells, however, ER was induced by DES, 17 beta-estradiol, testosterone
      or Tx 24 h after a single injection on day 0, but not by the injection of 5 alpha
      dihydrotestosterone, progesterone, or epidermal growth factor. ER in uterine
      epithelial cells was detected even 12 h after a single injection of 3 micrograms
      DES on day 0. ER mRNA expression of uterine and vaginal epithelial cells of
      newborn mice increased 4 h after a single injection of 3 micrograms DES. ER mRNA
      expression of uterine and vaginal stromal cells in neonatal mice increased 4 h
      after a single injection of 100 micrograms Tx. In uterine epithelial and stromal
      cells and vaginal epithelial cells of ovariectomized adult mice, ER mRNA
      expression increased 12 h after a single injection of 3 micrograms DES and 100
      micrograms Tx. CONCLUSIONS: The present study indicates that Tx acts as ER
      inducer in the uterus and vagina of neonatal and ovariectomized adult mice.
      However, responsiveness of reproductive tracts to Tx is different between newborn
      and adult mice.

PMID- 8742703
TI  - Foetal genital development in Hyrax capensis, a species with primary testicondia:
      proposal for the evolution of Hunter's gubernaculum.
AB  - BACKGROUND: Control of testicular descent is poorly understood. There are a
      number of mammalian species in which testis descent does not occur, and the
      phenomenon is called testicondia. Analysis of foetal development of such species
      could contribute to a better understanding of the key events in anatomical
      development underlying testis descent. Specific attention is to be given to the
      development of the so-called gubernaculum of Hunter: a structure of complex
      architecture and composition, which extends from the caudal pole of the
      mesonephric remnants into the inguinal abdominal wall and which is present in
      most mammals but not in submammalian vertebrates. METHODS: Serially sectioned
      male and female foetuses of Hyrax capensis, a species in which testes remain
      close to the caudal pole of the kidneys throughout life, were analysed for
      architecture of the developing genital apparatus and the immediately surrounding
      structures. The results of this analysis were compared with those from a similar
      analysis of reptiles, of monotremata without testis descent, and of mammals with
      testis descent. RESULTS: Reptiles and Monotremata showed no gubernacular
      structures. Mammals with testis descent showed gubernacular growth and
      differentiation which varied between the sexes and with the stage of foetal
      development. Hyrax capensis foetuses showed the development of only one component
      of the gubernaculum: the gubernacular cord as a part of the mesonephric mesentery
      and extending between the caudal pole of the mesonephros (or mesonephric remnants
      in older foetuses) and the lateral bladder ligament. No part developed in the
      inguinal abdominal wall components, which are the primordia of the cremaster sacs
      in species with testis descent. CONCLUSION: Hyrax capensis shows only partial
      development of the gubernacular structures, and, specifically, the primordia of
      the cremaster sacs remain absent. Thus, this species lacks a key anatomical
      condition for testis descent. Gubernacular architecture in Hyrax capensis seems
      of a degree intermediate between egg laying monotremata mammals and mammals with
      testis descent. A model is proposed within which to understand the development of
      the gubernacular components within the mammalian class.

PMID- 8742704
TI  - Human (and some other primates') uterine teres ligament represents a mammalian
      developmental novelty.
AB  - BACKGROUND: The primordia of the structures developing into the mammalian male
      cremaster sacs emerge as well in females fetuses. In most species the structures
      developing from these primordia in females remain inconspicuous: the so-called
      uterine teres ligament consisting of a slender part across the uterine broad
      ligament and a more or less developed bulbous structure at the site where this
      ligament inserts into the inguinal abdominal bottom. Not many data are available
      concerning the growth, development, or function of the uterine teres ligament. In
      humans--and also in other "higher" female primates--the uterine teres ligament is
      a major structure consisting mainly of smooth musculature. It is attached to the
      ventral aspect of the tubo-uterine junction. From there it courses across the
      uterine broad ligament and extends, retroperitoneally, to the inguinal region
      where it pierces through the inguinal canal to end in the tissues ventral of the
      pubic bones. OBSERVATIONS: Analysis of the fetal development of the human uterine
      teres ligament, as compared with that of various other non-primate mammals,
      offers an explanation for its unusual anatomical condition. Evidence is conferred
      that, in human fetuses, there is no counterpart for the slender ligament across
      the broad ligament in other mammals. Instead, the homologue of the rudimentary
      bulbous structure in the abdominal bottom of non-primate females develops into a
      strong muscular structure which is directly connected to the (para-)menonephric
      duct wall. CONCLUSION: It is concluded that the human uterine teres ligament is
      to be judged a structure different from that of other, non-primate, mammals. It
      is speculated that the unusual structure of the human teres ligament is related
      to one or more of the many unusual features of human uterine development: as a
      single organ (uterus simplex), with a position deep in the abdominal cavity below
      the pelvic brim, and far away from the posterior abdominal wall. The unusual
      anatomical position may require an unusual construction of the uterine suspensory
      apparatus of which the teres ligament is one component.

PMID- 8742705
TI  - Effect of neonatal exposure to diethylstilbestrol and tamoxifen on pelvis and
      femur in male mice.
AB  - BACKGROUND: Permanent abnormalities have been reported in reproductive and non
      reproductive organs of mice and humans exposed perinatally to a synthetic
      estrogen, diethylstilbestrol (DES). Recent studies demonstrated that sex hormones
      affected the shape of the innominate bone in mice. Therefore, we analyzed the
      long-term effects of neonatal exposure of DES and tamoxifen, an anti-estrogen, in
      mouse bones. METHODS: Changes in the pelvis and femur were examined in 1- to 15
      month-old C57BL/Tw male mice given 5 daily injections of 3 micrograms DES or of
      100 micrograms tamoxifen beginning on the day of birth by measuring contents of
      calcium (Ca) and phosphorus (P), and the numbers of osteoblasts and osteoclasts.
      RESULTS: The ash weight of pelvis and femur in neonatally DES- and tamoxifen
      treated mice was lower than that in the controls at 2-15 months of age. Contents
      of Ca and P of pelvis and femur in neonatally tamoxifen-treated mice were lower
      than in the controls and neonatally DES-treated mice. In neonatally DES-treated
      mice at 6-12 months, Ca and P contents in the pelvis were lower than in controls,
      but not different in the femur. The number of osteoblasts per unit length of
      endocortical surface of the femur in 2- and 3-month-old DES- and tamoxifen
      treated mice was lower than that in the controls. The osteoclast number in the
      femur in DES-treated mice at 2 to 12 months was not different from that in the
      controls; however, in tamoxifen-treated mice, the number was higher than in the
      controls. An epiphyseal line was clearly detected in the femur of 12- and 15
      month-old DES- and tamoxifen-treated male mice, whereas the line in the controls
      disappeared after 12 months. CONCLUSIONS: The present results indicate that in
      male mice, neonatal exposure to DES and tamoxifen induced permanent changes in
      the pelvis and the femur, and that tamoxifen had a greater effect on bone tissue
      than did DES.

PMID- 8742706
TI  - The AINTEGUMENTA gene of Arabidopsis required for ovule and female gametophyte
      development is related to the floral homeotic gene APETALA2.
AB  - Ovules play a central role in plant reproduction, generating the female
      gametophyte within sporophytic integuments. When fertilized, the integuments
      differentiate into the seed coat and support the development of the embryo and
      endosperm. Mutations in the AINTEGUMENTA (ANT) locus of Arabidopsis have a
      profound effect on ovule development. Strong ant mutants have ovules that fail to
      form integuments or a female gametophyte. Flower development is also altered,
      with a random reduction of organs in the outer three whorls. In addition, organs
      present in the outer three floral whorls often have abnormal morphology. Ovules
      from a weak ant mutant contain both inner and outer integuments but generally
      fail to produce a functional female gametophyte. We isolated the ANT gene by
      using a mutation derived by T-DNA insertional mutagenesis. ANT is a member of a
      gene family that includes the floral homeotic gene APETALA2 (AP2). Like AP2, ANT
      contains two AP2 domains homologous with the DNA binding domain of ethylene
      response element binding proteins. ANT is expressed most highly in developing
      flowers but is also expressed in vegetative tissue. Taken together, these results
      suggest that ANT is a transcription factor that plays a critical role in
      regulating ovule and female gametophyte development.

PMID- 8742707
TI  - AINTEGUMENTA, an APETALA2-like gene of Arabidopsis with pleiotropic roles in
      ovule development and floral organ growth.
AB  - To understand better the role of genes in controlling ovule development, a female
      sterile mutant, aintegumenta (ant), was isolated from Arabidopsis. In ovules of
      this mutant, integuments do not develop and megasporogenesis is blocked at the
      tetrad stage. As a pleiotropic effect, narrower floral organs arise in reduced
      numbers. More complete loss of floral organs occurs when the ant mutant is
      combined with the floral homeotic mutant apetala2, suggesting that the two genes
      share functions in initiating floral organ development. The ANT gene was cloned
      by transposon tagging, and sequence analysis showed that it is a member of the
      APETALA2-like family of transcription factor genes. The expression pattern of ANT
      in floral and vegetative tissues indicates that it is involved not only in the
      initiation of integuments but also in the initiation and early growth of all
      primorida except roots.

PMID- 8742708
TI  - Identification of an elicitor active site within the three-dimensional structure
      of the tobacco mosaic tobamovirus coat protein.
AB  - The coat protein (CP) of tobacco mosaic tobamovirus (TMV) elicits the
      hypersensitive response (HR) conferred by the N' gene from Nicotiana sylvestris.
      This study presents evidence demonstrating a critical role for a specific CP
      structural site in eliciting this HR. Based on the known structure of the TMV CP,
      specific substitutions were created within the CP of the elicitor strain P20L to
      identify structural areas essential for host recognition. Of 32 substitutions
      made, 14 conferred either a temperature-sensitive (loss of the HR at 29 degrees
      C) or a knockout (loss of the HR at 25 degrees C) HR phenotype in N.sylvestris.
      These essential residues were noncontiguous in position; however, within the
      three-dimensional CP structure, all resided primarily along the right face of the
      molecule's helical bundle. Substitutions that did not affect the HR phenotype
      either were located outside of this area or were conservative in change. In
      addition, placing two temperature-sensitive substitutions within the same CP
      resulted in lowering temperature sensitivity from 29 to 27 degrees C. This
      additive effect suggests that residues essential for HR elicitation contribute
      independently to host recognition. This feature is characteristic of recognition
      surfaces. The presence of a specific elicitor active site within the three
      dimensional structure of the TMV CP is consistent with binding of a host-encoded
      receptor and demonstrates the importance of CP structure in HR specificity.

PMID- 8742709
TI  - Ovule development: identification of stage-specific and tissue-specific cDNAs.
AB  - A differential screening approach was used to identify seven ovule-specific cDNAs
      representing genes that are expressed in a stage-specific manner during ovule
      development. The Phalaenopsis orchid takes 80 days to complete the sequence of
      ovule developmental events, making it a good system to isolate stage-specific
      ovule genes. We constructed cDNA libraries from orchid ovule tissue during
      archesporial cell differentiation, megasporocyte formation, and the transition to
      meiosis, as well as during the final mitotic divisions of female gametophyte
      development. RNA gel blot hybridization analysis revealed that four clones were
      stage specific and expressed solely in ovule tissue, whereas one clone was
      specific to pollen tubes. Two other clones were not ovule specific. Sequence
      analysis and in situ hybridization revealed the identities and domain of
      expression of several of the cDNAs. O39 encodes a putative homeobox transcription
      factor that is expressed early in the differentiation of the ovule primordium;
      O40 encodes a cytochrome P450 monooxygenase (CYP78A2) that is pollen tube
      specific. O108 encodes a protein of unknown function that is expressed
      exclusively in the outer layer of the outer integument and in the female
      gametophyte of mature ovules. O126 encodes a glycine-rich protein that is
      expressed in mature ovules, and O141 encodes a cysteine proteinase that is
      expressed in the outer integument of ovules during seed formation. Sequences
      homologous to these ovule clones can now be isolated from other organisms, and
      this should facilitate their functional characterization.

PMID- 8742710
TI  - Isolation of Arabidopsis genes that differentiate between resistance responses
      mediated by the RPS2 and RPM1 disease resistance genes.
AB  - The Arabidopsis disease resistance gene RPS2 is involved in recognition of
      bacterial pathogens carrying the avirulence gene avrRpt2, and the RPM1 resistance
      gene is involved in recognition of pathogens carrying avrRpm1 or avrB. We
      identified and cloned two Arabidopsis genes, AIG1 and AIG2 (for avrRpt2-induced
      gene), that exhibit RPS2- and avrRpt2-dependent induction early after infection
      with Pseudomonas syringae pv maculicola strain ES4326 carrying avrRpt2. However,
      ES4326 carrying avrRpm1 or avrB did not induce early expression of AIG1 and AIG2.
      Conversely, ES4326 carrying avrRpm1 or avrB induced early expression of the
      previously isolated defense-related gene ELI3, whereas ES4326 carrying avrRpt2
      did not. The induction patterns of the AIG genes and ELI3 demonstrate that
      different resistance gene-avr gene combinations can elicit distinct defense
      responses. Furthermore, by examining the expression of AIG1 and ELI3 in plants
      infiltrated with a mixed inoculum of ES4326 carrying avrRpt2 and ES4326 carrying
      avrRpm1, we found that there is interference between the RPS2- and RPM1-mediated
      resistance responses.

PMID- 8742711
TI  - Okadaic acid, a protein phosphatase inhibitor, blocks calcium changes, gene
      expression, and cell death induced by gibberellin in wheat aleurone cells.
AB  - The cereal aleurone functions during germination by secreting hydrolases, mainly
      alpha-amylase, into the starchy endosperm. Multiple signal transduction pathways
      exist in cereal aleurone cells that enable them to modulate hydrolase production
      in response to both hormonal and environmental stimuli. Gibberellic acid (GA)
      promotes hydrolase production, whereas abscisic acid (ABA), hypoxia, and osmotic
      stress reduce amylase production. In an effort to identify the components of
      transduction pathways in aleurone cells, we have investigated the effect of
      okadaic acid (OA), a protein phosphatase inhibitor, on stimulus-response coupling
      for GA, ABA, and hypoxia. We found that OA (100 nM) completely inhibited all the
      GA responses that we measured, from rapid changes in cytosolic Ca2+ through
      changes in gene expression and accelerated cell death. OA (100 nM) partially
      inhibited ABA responses, as measured by changes in the level of PHAV1, a cDNA for
      an ABA-induced mRNA in barley. In contrast, OA had no effect on the response to
      hypoxia, as measured by changes in cytosolic Ca2+ and by changes in enzyme
      activity and RNA levels of alcohol dehydrogenase. Our data indicate that OA
      sensitive protein phosphatases act early in the transduction pathway of GA but
      are not involved in the response to hypoxia. These data provide a basis for a
      model of multiple transduction pathways in which the level of cytosolic Ca2+ is a
      key point of convergence controlling changes in stimulus-response coupling.

PMID- 8742713
TI  - A jojoba beta-Ketoacyl-CoA synthase cDNA complements the canola fatty acid
      elongation mutation in transgenic plants.
AB  - beta-Ketoacyl-coenzyme A (CoA) synthase (KCS) catalyzes the condensation of
      malonyl-CoA with long-chain acyl-CoA. This reaction is the initial step of the
      microsomal fatty acyl-CoA elongation pathway responsible for formation of very
      long chain fatty acids (VLCFAs, or fatty acids with chain lengths > 18 carbons).
      Manipulation of this pathway is significant for agriculture, because it is the
      basis of conversion of high erucic acid rapeseed into canola. High erucic acid
      rapeseed oil, used as an industrial feedstock, is rich in VLCFAs, whereas the
      edible oil extracted from canola is essentially devoid of VLCFAs. Here, we report
      the cloning of a cDNA from developing jojoba embryos involved in microsomal fatty
      acid elongation. The jojoba cDNA is homologous to the recently cloned Arabidopsis
      FATTY ACID ELONGATION1 (FAE1) gene that has been suggested to encode KCS. We
      characterize the jojoba enzyme and present biochemical data indicating that the
      jojoba cDNA does indeed encode KCS. Transformation of low erucic acid rapeseed
      with the jojoba cDNA restored KCS activity to developing embryos and altered the
      transgenic seed oil composition to contain high levels of VLCFAs. The data reveal
      the key role KCS plays in determining the chain lengths of fatty acids found in
      seed oils.

PMID- 8742712
TI  - A soybean sucrose binding protein independently mediates nonsaturable sucrose
      uptake in yeast.
AB  - Heterologous expression of a cDNA encoding a 62-kD soybean sucrose binding
      protein in yeast demonstrates that this protein, independent of other plant
      proteins, mediates sucrose uptake across the plasma membrane. Sucrose binding
      protein-mediated sucrose uptake is nonsaturable up to 30 mM sucrose, is specific
      for sucrose, and is relatively insensitive to treatment with sulfhydryl-modifying
      reagents. Alteration of the external pH or pretreatment of the yeast cells with
      protonophores did not significantly affect the rate of 14C-sucrose uptake. This
      demonstrates that sucrose binding protein-mediated sucrose uptake is not
      dependent on H+ movement and delineates it from other plant sucrose transporters.
      Physiological characterization of sucrose uptake into higher plant cells has
      shown the presence of both saturable and nonsaturable uptake components. The
      nonsaturable mechanism is relatively insensitive to external pH, pretreatment
      with protonophores, and treatment with sulfhydryl-modifying reagents. Sucrose
      binding protein-mediated sucrose uptake in yeast mimics this physiologically
      described, but mechanistically undefined, nonsaturable sucrose uptake mechanism
      in higher plants. Functional characterization of the sucrose binding protein thus
      defines both a novel component of sucrose uptake and provides important insight
      into this nonsaturable sucrose uptake mechanism, which has remained enigmatic
      since its physiological description.

PMID- 8742714
TI  - The regulator of MAT2 (ROM2) protein binds to early maturation promoters and
      represses PvALF-activated transcription.
AB  - The regulation of maturation (MAT)- and late embryogenesis (LEA)-specific gene
      expression in dicots involves factors related to ABI3, a seed-specific component
      of the abscisic acid signal transduction pathways from Arabidopsis. In French
      bean (Phaseolus vulgaris), the ABI3-like factor, PvALF, activates transcription
      from MAT promoters of phytohemagglutinin (DLEC2) and beta-phaseolin (PHS beta)
      genes. We describe the regulator of MAT2 (ROM2) as a basic leucine zipper (bZIP)
      DNA binding protein that recognizes motifs with symmetric (ACGT) and asymmetric
      (ACCT) core elements present in both MAT promoters. ROM2 antagonizes trans
      activation of the DLEC2 promoter by PvALF in transient expression assays.
      Repression was abolished by mutations that prevented binding of ROM2 to the DLEC2
      seed enhancer region. Moreover, a hybrid protein composed of a PvALF activation
      domain and the DNA binding and dimerization domain of ROM2 activated gene
      expression, indicating that ROM2 recognizes the DLEC2 enhancer in vivo;
      consequently, ROM2 functions as a DNA binding site-dependent repressor.
      Supershift analysis of nuclear proteins, using a ROM2-specific antibody, revealed
      an increase in ROM2 DNA binding activity during seed desiccation. A corresponding
      increase in ROM2 mRNA coincided with the period when DLEC2 mRNA levels declined
      in embryos. These results demonstrate developmental regulation of the ROM2
      repressor and point to a role for this factor in silencing DLEC2 transcription
      during late embryogenesis.

PMID- 8742715
TI  - Tomato annexins p34 and p35 bind to F-actin and display nucleotide
      phosphodiesterase activity inhibited by phospholipid binding.
AB  - Annexins are a family of proteins found in a range of eukaryotic cell types. They
      share a characteristic amino acid sequence and a Ca(2+)-dependent affinity for
      specific phospholipids. In plants, proteins with common properties and
      significant homology with annexins have been identified in a number of species
      and implicated in diverse cellular functions known to be modulated by Ca2+. This
      study describes several novel biochemical properties of the tomato annexins p34
      and p35 that are relevant to our understanding of their functions in the plant.
      First, the annexins were found to bind to actin in a calcium- and pH-dependent
      interaction that was specific for F-actin and not G-actin. Second, an enzyme
      activity defined as a nucleotide phosphodiesterase activity was found associated
      with the purified annexin preparation. Selective immunoprecipitation of p34 and
      p35 strongly suggests that the enzyme activity is a property of the annexins and
      constitutes 60% of the total soluble activity found in root extracts capable of
      hydrolyzing free ATP. The substrate specificity of the enzyme within in vitro
      assays is broad. ATP is the preferred substrate, but nearly identical rates of
      hydrolysis of GTP and substantial hydrolysis of other nucleotide tri- and
      diphosphates are observed. The enzyme activity was found to be a property of both
      p34 and p35, although the specific activity was routinely higher for p34. Third,
      the enzyme activity of the annexins was not affected by F-actin binding but could
      be abolished by the specific Ca(2+)-dependent interaction of the annexins with
      phospholipids. Our results showed that p34 and p35 account for substantial enzyme
      activity in tomato root cells. This activity was exhibited when the proteins were
      either in soluble form or attached to actin filaments. Enzyme activity was not
      exhibited when the annexins were bound to phospholipids. These properties suggest
      a role for the proteins in mediating Ca(2+)-dependent events involving
      interactions of the cytoskeleton and cellular membranes.

PMID- 8742716
TI  - Advances in computational image processing for microscopy.
AB  - The field of electron microscopy applied to structural biology has made
      significant progress in the last 5 years, with many labs attempting the solution
      of ever more challenging problems. This work has demanded significant new
      resources for the computational analysis of the data collected from the
      microscope. The purpose of this paper is to review briefly the state of the art
      in image processing of microscope data and to serve as an introduction to this
      special issue of the journal.

PMID- 8742717
TI  - MRC image processing programs.
AB  - Digital image processing is an essential step in the determination of
      macromolecular structures by electron microscopy. Centrally important procedures
      are the averaging of many images of the subunit to improve the signal, the
      correction for various transfer functions, and the generation of a three
      dimensional map from a set of two-dimensional projections. The detailed way in
      which these computational procedures are best carried out depends on the symmetry
      of the object and the type of specimen preparation. Over many years a large set
      of programs has been written by various members of the Laboratory of Molecular
      Biology for processing images of two-dimensional crystals and of particles with
      helical or icosahedral symmetry. The philosophy has been to write stand-alone
      programs and the whole system is given coherence by the adoption of standard
      formats for the storage and interchange of different kinds of data. This paper
      describes the current state of the programs.

PMID- 8742718
TI  - A new generation of the IMAGIC image processing system.
AB  - One of the aims of modern microscopy is to quantify two-, three-, or even four
      dimensional phenomena in biology, medicine, and material sciences. The
      requirements imposed on software by such data processing are exemplified by the
      design considerations of the IMAGIC-5 software system. This system includes
      facilities for multivariate statistical analysis of large data sets, for
      correlation averaging of two-dimensional crystals, and for three-dimensional
      reconstruction of macromolecular structures. The molecules may be arranged as two
      dimensional crystals, as helices, or as single particles with arbitrary
      pointgroup symmetry. IMAGIC's novel angular reconstitution approach allows for
      the rapid determination of three-dimensional structures of uncrystallized
      molecules to high resolution. The general organization, user interaction
      strategy, file structure, and extendibility of IMAGIC are discussed and
      illustrated with some practical examples.

PMID- 8742719
TI  - The flying cylinder: a new algorithm for filament recognition in noisy stereo
      images.
AB  - We present a new method of automatic 3D filament representation which uses stereo
      micrographs to reconstruct three-dimensional trajectories of filament-like
      objects as DNA molecules. The method deals with low contrasted and noisy images,
      as obtained from cryovitrified samples by means of electron microscopy. The three
      dimensional information is extracted from skeletizing simultaneously both images
      of a given stereo-pair, instead of processing them separately. The main
      advantages of the technique are reproducibility and speed, compared to the
      reconstruction done by manual registration, i.e., clicking on the stereo
      micrographs.

PMID- 8742720
TI  - The micrograph data processing program.
AB  - MDPP is a fully featured general-purpose image processing package primarily
      written to support research in structural biology using data gathered by electron
      microscopy. It has focused on the analysis of images using Fourier techniques,
      particularly periodic plane-layer and helical structures, but has extensive tools
      for other processing options (e.g., point-counting, image quantitation, DNA
      sequencing, and display). Three-dimensional reconstruction methods are supported,
      including iterative deconvolution schemes for light micrographs. The basic
      program is command line-driven, but the user can choose to write sophisticated
      command scripts and use a menu-driven full-screen or Motif interface to call
      them. Color images are supported with both color palette and RGB options.
      Extensive documentation is accessible from within the program as online HELP and
      also as HTML. Care has been taken to support interfaces to other image processing
      packages, e.g., MacIntosh applications via the TIFF image format, and other EM
      targeted image processing packages. The paper provides an overview of the
      program, its design, and implementation and outlines future plans for software
      development. Some general issues concerning image processing program design are
      discussed.

PMID- 8742721
TI  - PTOOL: a software package for the selection of particles from electron
      cryomicroscopy spot-scan images.
AB  - PTOOL, a suite of tools packaged in an X Window System-based graphical user
      interface has been developed to allow consistent and accurate selection of single
      particles from low-contrast spot-scan and flood beam electron microscopy images.
      These user friendly and computationally efficient tools run on Unix-based
      workstations. Particles are selected using an automatic reference based selection
      method which incorporates extensive image preprocessing. An image division and
      subsequent image sewing mechanism allows for efficient particle selection
      independent of micrograph size. A particle viewing tool is provided which
      displays galleries of images and has options for performing image processing
      operations such as Fourier filtering, histogram equalization, and image masking.
      In addition, a tool is included to perform semiautomatic focal pair particle
      matching to identify the same particles on two micrographs.

PMID- 8742722
TI  - Three-dimensional reconstruction of icosahedral particles--the uncommon line.
AB  - The past few years have seen an explosion in the number of viral structures
      determined by icosahedral reconstruction from cryoelectron micrographs. The
      success of this work has depended upon a combination of the high-fidelity but low
      contrast information contained in these images with efficient algorithms for
      determining particle orientation and three-dimensional structure. This review
      describes the principles behind the most commonly used method of reconstruction
      of the icosahedral particles and the method's implementation in an icosahedral
      reconstruction program suite.

PMID- 8742723
TI  - IVE (Image Visualization Environment): a software platform for all three
      dimensional microscopy applications.
AB  - IVE (Image Visualization Environment) is a software platform designed from the
      outset to handle all aspects of modern computerized multidimensional microscopy.
      This platform provides users with an execution environment in which 5D data (XYZ,
      wavelength, and time) can be easily manipulated for the purpose of data
      collection, processing, display, and analysis. During the entire process,
      powerful data display functions are readily available for extracting complicated
      three-dimensional information through data visualization. By employing both the
      shared memory and multitasking features of the UNIX operation system, individual
      functions can be implemented as separate programs, and multiple programs can
      access the same data pool simultaneously. This enables users to combine the
      functionalities of different programs to facilitate each unique data analysis
      task. Furthermore, by defining an appropriate program execution model, commonly
      shared functional components such as data display, data I/O and user interface,
      etc. can be implemented using simple IVE library calls. This dramatically reduces
      the program development time and ensures consistency throughout the entire
      software system. As a result, users can quickly master the microscopy software
      system and new functions can be easily integrated, as different functional
      requirements arise for different research projects.

PMID- 8742724
TI  - Digital image processing of electron micrographs: the PIC system-III.
AB  - The PIC system is an integrated package of image processing software written in
      Fortran and C. Throughout its 16 years of continuous development, PIC has been
      designed for the processing of electron micrographs with emphasis on the
      particular requirements for structural analysis of biological macromolecules. PIC
      has been implemented on successive generations of Digital Equipment Corporation
      dedicated minicomputers and workstations. The latest version, PIC-III, runs on
      Alpha workstations and represents a substantial upgrading in functionality
      compared with PIC-II, the VAX version previously described (B.L. Trus et al.
      (1992), Scanning Microsc. Suppl. 6, 441-451). PIC now possesses an X-windows menu
      driven graphical user interface that many be utilized from both local or remote X
      window terminals or workstations. Other new features include dynamic memory
      allocation; an open systems approach to interfacing with other image processing
      software packages; interface options with visualization software; and programs to
      reconstruct three-dimensional density maps of both helical filaments and free
      standing particles with and without symmetry.

PMID- 8742725
TI  - A brief description of I.C.E.: the integrated crystallographic environment.
AB  - We describe the current status of the program I.C.E., the Integrated
      Crystallographic Environment. I.C.E. is a windows-based, menu-driven image
      processing package mainly aimed toward crystallographic image processing,
      although some of its functions have been used in analyzing single particle data
      and helical objects. The system can take individual images of crystals through
      the entire process of data analysis, from windowing the raw image through to the
      final evaluation of defocus, symmetry and creation of projection reconstructions.
      Current plans are to incorporate a three-dimensional database of images and
      electron diffraction patterns, and 3-D merging and visualization.

PMID- 8742726
TI  - Computer visualization of three-dimensional image data using IMOD.
AB  - We have developed a computer software package, IMOD, as a tool for analyzing and
      viewing three-dimensional biological image data. IMOD is useful for studying and
      modeling data from tomographic, serial section, and optical section
      reconstructions. The software allows image data to be visualized by several
      different methods. Models of the image data can be visualized by volume or
      contour surface rendering and can yield quantitative information.

PMID- 8742727
TI  - NewVision: a program for interactive navigation and analysis of multiple 3-D data
      sets using coordinated virtual cameras.
AB  - We describe "NewVision", a program designed for rapid interactive display,
      sectioning, and comparison of multiple large three-dimensional (3-D)
      reconstructions. User tools for navigating within large 3-D data sets and
      selecting local subvolumes for display, combined with view caching, fast integer
      interpolation, and background tasking, provide highly interactive viewing of
      arbitrarily sized data sets on Silicon Graphics systems ranging from simple
      workstations to supercomputers. Multiple windows, each showing different views of
      the same 3-D data set, are coordinated through mapping of local coordinate
      systems to a single global world coordinate system. Mapping to a world coordinate
      system allows quantitative measurements from any open window as well as creation
      of linked windows in which operations such as panning, zooming, and 3-D rotations
      of the viewing perspective in any one window are mirrored by corresponding
      transformations in the views shown in other linked windows. The specific example
      of tracing 3-D fiber trajectories is used to demonstrate the potential of the
      linked window concept. A global overview of NewVision's design and organization
      is provided, and future development directions are briefly discussed.

PMID- 8742728
TI  - Real-time isocontouring and texture mapping meet new challenges in interactive
      molecular graphics applications.
AB  - A technique to extract solid isosurfaces from three-dimensional electron density
      data at high speed is presented. The ability to change the contouring threshold
      in real time renders the method a powerful tool for interactive analysis of
      proteins and their supramolecular assemblies, in order to compare and combine
      structural information gathered by different data acquisition methods. Chemical
      properties can effectively be mapped onto these isosurfaces by the use of texture
      mapping. The implications of these methods in combination with other
      visualization techniques are discussed, and a framework for their integration
      into a general-purpose molecular graphics toolkit is proposed.

PMID- 8742729
TI  - Sterecon--three-dimensional reconstructions from stereoscopic contouring.
AB  - Sterecon is a system for making 3-D reconstructions or measurements by tracing
      from stereopair images. The stereopair images may come directly from a
      microscope, such as a transmission or scanning electron microscope.
      Alternatively, the images may be created from a stack of thin slices, such as a
      confocal light microscopy depth series, an electron tomographic volume, or a set
      of serial histological slices. When the structure to be studied is thick or
      complex, a serial stack of stereoscopic images can be used. Objects are traced
      within the images, and their coordinates are entered into a line or contour
      database. The contour database can be used for 3-D structure measurement, and the
      contours can be displayed as a reconstruction. Sterecon has interfaces from other
      software which can generate the input images and to other software for further
      display and analysis.

PMID- 8742730
TI  - AVS software for visualization in molecular microscopy.
AB  - AVS (Application Visualization System) is commercially available software for
      analyzing and viewing data. AVS is primarily used in the physical sciences and
      engineering, and here we describe the application of AVS for examining three
      dimensional density maps generated by electron microscopy and image processing.
      For this purpose, AVS can be applied with relative ease, even though the software
      is indeed quite sophisticated. The primary advantage is that visualization
      applications can be generated by combining software components, called modules,
      into executable flow networks. Simple networks are described for generating
      ribbon diagrams of macromolecules, surface-shaded views, and contour maps. Easy
      to use dials, bar sliders, and buttons provide tremendous versatility for real
      time manipulation of isosurface values, depth cueing, view orientation, size, and
      animation. In addition, AVS supplies a framework for building new modules in C or
      FORTRAN. Modules for excavation and cropping provide tools that are particularly
      useful for extracting segments of a map and for examining maps of supramolecular
      complexes such as viruses. We describe a number of modules we have designed for
      analysis of three-dimensional data sets, as well as modules for importing image
      data from other software packages into AVS. We also describe xformat, a stand
      alone file conversion utility designed to allow import of a variety of image and
      map file formats into AVS.

PMID- 8742731
TI  - Helical processing using PHOELIX.
AB  - We describe here a set of procedures and algorithms for helical processing that
      we refer to as the PHOELIX package. The package was developed to provide a time
      efficient and semiautomated method for determining a three-dimensional density
      map from a specimen with helical symmetry. The procedures which are part of
      PHOELIX are drawn from the original MRC helical processing suite with extensions
      principally developed using the SUPRIM image processing package. The package in
      its current form has been optimized for the processing of actomyosin filaments
      but has been modified and applied to other helical structures.

PMID- 8742732
TI  - A flexible environment for the visualization of three-dimensional biological
      structures.
AB  - "Ducky" is a flexible and versatile software system for processing, rendering,
      and animating 3D datasets. The system is based on a powerful run-time interpreted
      language similar to C. The language includes many built-in functions for
      animation, rendering, shading, surface definition, and the creation of
      interactive menu and window-based visualization environments. Both volume and
      surface rendering methods are provided and may be combined in a single
      visualization. Ducky can create animations of a sequence of different views of a
      structure either within a 3D volume or across a series of volumes. Scripts
      implementing several common visualization tasks are provided. The system is
      readily extendible. Existing scripts can be modified or new scripts written to
      create additional interactive environments and processes.

PMID- 8742733
TI  - A model-based approach for determining orientations of biological macromolecules
      imaged by cryoelectron microscopy.
AB  - A polar Fourier transform (PFT) method is described that facilitates
      determination and refinement of orientations of individual biological
      macromolecules imaged with cryoelectron microscopy techniques. A three
      dimensional density map serves as a high signal-to-noise model from which a PFT
      database of different views is generated and against which the PFTs of individual
      images are correlated. The PFT produces rotation-invariant data particularly well
      suited for rapid and accurate determination of orientation parameters. The method
      relies on accurate knowledge of the center of symmetry and radial scale of both
      model and image data but is insensitive to the relative contrast and background
      values of these data. Density maps may be derived from a variety of sources such
      as computer-generated models, X-ray crystallographic structures, and three
      dimensional reconstructions computed from images. The PFT technique has been
      particularly useful for the analysis of particles with icosahedral symmetry and
      could be adapted for the analysis of single particles of any symmetry for which a
      crude model exists or can be produced.

PMID- 8742734
TI  - SUPRIM: easily modified image processing software.
AB  - A flexible, modular software package intended for the processing of electron
      microscopy images is presented. The system consists of a set of image processing
      tools or filters, written in the C programming language, and a command line style
      user interface based on the UNIX shell. The pipe and filter structure of UNIX and
      the availability of command files in the form of shell scripts eases the
      construction of complex image processing procedures from the simpler tools.
      Implementation of a new image processing algorithm in SUPRIM may often be
      performed by construction of a new shell script, using already existing tools.
      Currently, the package has been used for two- and three-dimensional image
      processing and reconstruction of macromolecules and other structures of
      biological interest.

PMID- 8742735
TI  - The contour-buildup algorithm to calculate the analytical molecular surface.
AB  - A new algorithm is presented to calculate the analytical molecular surface
      defined as a smooth envelope traced out by the surface of a probe sphere rolled
      over the molecule. The core of the algorithm is the sequential build up of multi
      arc contours on the van der Waals spheres. This algorithm yields substantial
      reduction in both memory and time requirements of surface calculations. Further,
      the contour-buildup principle is intrinsically "local", which makes calculations
      of the partial molecular surfaces even more efficient. Additionally, the
      algorithm is equally applicable not only to convex patches, but also to concave
      triangular patches which may have complex multiple intersections. The algorithm
      permits the rigorous calculation of the full analytical molecular surface for a
      100-residue protein in about 2 seconds on an SGI indigo with R4400++ processor at
      150 Mhz, with the performance scaling almost linearly with the protein size. The
      contour-buildup algorithm is faster than the original Connolly algorithm an order
      of magnitude.

PMID- 8742736
TI  - Processing of electron diffraction patterns acquired on a slow-scan CCD camera.
AB  - We have developed two software packages for the processing of electron
      diffraction patterns acquired on a slow-scan CCD camera. Automated indexing and
      processing of these electron diffraction patterns is possible using a program
      called AUTO. To obtain a set of reliable reflections, AUTO applies a number of
      corrections, which are necessary due to the acquisition of the patterns with a
      slow-scan CCD camera. To index and process unknown lattices in electron
      diffraction patterns obtained from, for instance, a new protein or a new crystal
      form, an interactive program called EDP is available. It supports indexing in an
      interactive manner through a graphical user interface. Processing of the electron
      diffraction pattern is done using a script created by EDP. Both packages run on
      UNIX platforms, with EDP requiring the X Window System.

PMID- 8742737
TI  - 3-D TOP-A software package for the topological analysis of image sequences.
AB  - The software package 3-D TOP is a measurement software which has been developed
      to meet the needs of those who analyze mechanical serial sections in histology
      and optical sections in laser scanning microscopy. The semiautomatic definition
      of topological centerlines is the backbone of this software. The three basic
      advantages in using the concept of topology are (a) resolving ambiguities for
      surface rendering, (b) flexible definition of objects for automatic
      identification, labeling, and measurement, and (c) topological quantification of
      complex forms. A specific application of this software to lung research is
      demonstrated.

PMID- 8742738
TI  - Extensible and object-oriented system Eos supplies a new environment for image
      analysis of electron micrographs of macromolecules.
AB  - To study macromolecular structure by electron microscopy, a highly extensible and
      object-oriented system has been developed for image analysis. This system is
      named "Eos" (Extensible and object-oriented system). The system described here
      supplies an environment with four types of supports: (i) a group of small tools
      for image analysis, (ii) tools for integration of small tools, such as
      "Display2," (iii) tools for development, such as "maketool," and (iv) object
      oriented libraries for development of new tools. Using Eos, electron micrographs
      can be analyzed by small tools and integration tools. In addition, Eos can be
      used to develop new tools based on new ideas because development tool and object
      oriented libraries are provided. The examples of implemented small tools for
      image analysis include three-dimensional reconstruction of objects with helical
      symmetry, cluster analysis, and contour expression.

PMID- 8742739
TI  - Proposal for a new distributed database of macromolecular and subcellular
      structures from different areas of microscopy.
AB  - In this work we address the problem of information access that arises in the
      field of three-dimensional structure determination, by means of image processing,
      from data obtained by various types of microscopy. A prototype of a distributed
      database containing three-dimensional structural information is presented. In
      this database the volume information is linked, if possible, to other sources of
      catalogued information such as sequence data, atomic coordinates, and
      bibliographies. The solution we propose is sufficiently general to be applicable
      to data in other fields of biomedical science.

PMID- 8742740
TI  - Image analysis of helical objects: the Brandeis Helical Package.
AB  - Although the fundamental steps in Fourier-based image analysis of electron
      micrographs of helical structures have not changed significantly since the
      techniques were developed 30 years ago, there have been developments which aid
      both the analysis itself and the interpretation of results. Increases in
      computational resources have allowed the automation of many of the repetitive
      steps in image processing. We describe here a set of computer programs which have
      been developed at Brandeis University over the past 10 or more years. These
      programs, referred to as the Brandeis Helical Package, are designed to operate
      independently of each other with a simple and more uniform protocol for the flow
      of information between them. The programs are now easier to understand and to use
      and therefore represent a good tool for the analysis of helical structures.

PMID- 8742741
TI  - COSAS 2.0--a Macintosh-based stereological analysis system.
AB  - Quantitation of morphological data is a component of both basic and clinical
      research. Often it is necessary to extract three-dimensional information from two
      dimensional images. Stereological analysis, the most reliable means of achieving
      this, is also increasingly used as a diagnostic tool in pathology. COSAS, a
      COmputerized Stereological Analysis System, is software which allows rapid
      recording of morphological data from two-dimensional images and performance of
      analyses necessary for both quantitation and three-dimensional interpretation.
      COSAS is reliable and easy to use. It was previously available in a VAX-based
      version (Cornacchia and Black, 1988). An improved version, COSAS 2.0, is now
      available for use on the Macintosh. COSAS 2.0 is considerably more "user
      friendly" and flexible than the VAX version of the program. COSAS 2.0 eliminates
      the necessity for the user to be linked with a large computer. COSAS 2.0 has the
      ability to interface with other commercially available software for scanned
      images (e.g., Adobe Photoshop, NIH-Image) and data manipulation (e.g., EXCEL,
      Delta Graphics). These features make it useful to both research and clinical
      laboratories. Although designed for the biologist, the system may be used to
      study cross sections of any solid. It could be of interest to material
      scientists, petrographers, and ceramicists, all of whom need to obtain
      quantitative information about three-dimensional spatial organization from two
      dimensional sections or projections.

PMID- 8742742
TI  - Toward fully automated high-resolution electron tomography.
AB  - Electron tomography is a powerful tool in elucidating the three-dimensional
      architecture of large biological complexes and subcellular organelles. Its use
      can be expanded through the simplification of the tomographic procedure by
      automation of its tasks. In this paper, we describe our EMACT/EMCAT system, which
      automates both tomographic data collection and reconstruction.

PMID- 8742743
TI  - SPIDER and WEB: processing and visualization of images in 3D electron microscopy
      and related fields.
AB  - The SPIDER system has evolved into a comprehensive tool set for image processing,
      making use of modern graphics interfacing in the VMS and UNIX environment. SPIDER
      and WEB handle the complementary tasks of batch processing and visualization of
      the results. The emphasis of the SPIDER system remains in the area of single
      particle averaging and reconstruction, although a variety of other application
      areas have been added. Novel features are a suite of operations relating to the
      determination, modeling, and correction of the contrast transfer function and the
      availability of the entire documentation in hypertext format.

PMID- 8742744
TI  - Visualization of three-dimensional density maps reconstructed from cryoelectron
      micrographs of viral capsids.
AB  - Full evaluation of three-dimensional density maps calculated from cryoelectron
      micrographs of complex supramolecular structures requires that the maps be sifted
      by a variety of complementary visualization techniques. We present here a primer
      for a number of such techniques in current widespread use, including surface
      rendering; serial sections; simulated motion; and real-time manipulation of tiled
      surfaces displayed on an advanced workstation. The principles on which these
      techniques operate are briefly reviewed, as are their advantages and limitations,
      with emphasis on the requirements for visual representation of viral capsid
      structures. These methods are illustrated in application to a density map of
      herpes simplex virus type 1 (HSV-1) capsid at 24 A resolution, which reveals more
      detailed information than heretofore concerning the inner surface of the
      icosahedral capsid shell and the 150-A-long channels that pass through each of
      the 162 capsomers.

PMID- 8742745
TI  - Automated software package for icosahedral virus reconstruction.
AB  - The three-dimensional reconstruction of icosahedral viruses from electron
      micrograph images has become an important tool for understanding virus structure,
      function, and pathogenesis. We have developed an integrated suite of software
      programs to automate most of the operations involved in producing these
      reconstructions from EM images. Our package combines the analytical capabilities
      of preexisting algorithms together with approaches we have developed to produce
      an interactive working environment which enhances the efficiency and usefulness
      of this approach to the structural analysis of icosahedral viruses.

PMID- 8742746
TI  - CTF determination of images of ice-embedded single particles using a graphics
      interface.
AB  - We implement a graphical user interface in an X-window/UNIX environment to
      compute and display the incoherently averaged Fourier transforms of electron
      images of single particles embedded in ice and the simulated contrast transfer
      function with or without envelope functions. This interface provides an easy and
      efficient operation for the determination of defocus value and the evaluation of
      the extent of Fourier amplitude falloff. This computational procedure is crucial
      for prescreening image data and performing image correction of contrast transfer
      function in high-resolution three-dimensional reconstruction of single particles.

PMID- 8742748
TI  - Software for 3-D reconstruction from images of oblique sections through 3-D
      crystals.
AB  - Oblique section reconstruction can produce a 3-D image from electron micrographs
      of a sectioned crystal when the orientation of the section plane is not aligned
      with the principal planes of the unit cell. We describe here the reconstruction
      protocol and the specialized computer software for a Fourier space method that
      can extract 3-D information from 2-D projection images of oblique sections. The
      protocol encompasses correction for image defects and image distortions,
      determination and refinement of reciprocal lattices, calculation of the crystal
      orientation in 3-D space, extraction of periodic information, alignment in
      Fourier space, determination and deconvolution of section thickness, and
      calculation of structure factors of the original crystal. A 3-D map of the unit
      cell can then be computed by standard crystallographic procedures. Oblique
      section reconstruction provides an alternative to tomography for 3-D imaging of
      crystalline objects with large unit cells. The method provides an excellent means
      of obtaining a 3-D transform using electron microscopy for comparison with X-ray
      diffraction data from native specimens.

PMID- 8742747
TI  - Presentation of the SIGMA software: Software of Imagery and Graphics for
      Molecular Architecture.
AB  - Sigma (Software of Imagery and Graphics for Molecular Architecture) is a software
      package designed for visualization and exploration of three-dimensional (3D)
      molecular electron microscopy data. It comprises a text and two graphic modes. In
      the text mode, a language allows the writing of scripts for repetitive tasks. The
      two graphic modes are based on the multiwindow environment with a mouse as
      pointer. The first graphic mode is dedicated to vectorial objects and the second
      to pixel/voxel objects. The data imported by SIGMA have various origins such as
      3D reconstruction volumes, Protein Data Bank data, or geometrical objects like
      spheres, cubes, or cylinders. These 3D objects are interactively rotated,
      translated, and rendered with SIGMA. This software, written in C language, runs
      on Silicon Graphics workstations using the X-Window plus Motif environment. The
      specific 3D routines are based on the Silicon Graphics GL library.

PMID- 8742749
TI  - d'Arsonval Medal: introduction. Om P. Gandhi: 1995 recipient of the d'Arsonval
      Medal.

PMID- 8742750
TI  - d'Arsonval Medal: address. some bioelectromagnetics research at the University of
      Utah: acceptance speech on the occasion of receiving the d'Arsonval Medal.

PMID- 8742751
TI  - Magnetic fields at resonant conditions for the hydrogen ion affect neurite
      outgrowth in PC-12 cells: a test of the ion parametric resonance model.
AB  - PC-12 cells primed with nerve growth factor (NGF) were exposed to sinusoidal
      extremely-low-frequency (ELF) magnetic fields (MFs) selected to test the
      predictions of the ion parametric resonance (IPR) model under resonance
      conditions for a single ion (hydrogen). We examined the field effects on the
      neurite outgrowth (NO) induced by NGF using three different combinations of flux
      densities of the parallel components of the AC MF (Bac) and the static MF (Bdc).
      The first test examined the NO response in cells exposed to 45 Hz at a Bdc of
      2.96 microT with resonant conditions for H+ according to the model. The Bac
      values ranged from 0.29 to 4.11 microT root-mean-square (rms). In the second
      test, the MF effects at off-resonance conditions (i.e., no biologically
      significant ion at resonance) were examined using the frequency of 45 Hz with a
      Bdc of 1.97 microT and covering a Bac range between 0.79 and 2.05 microT rms. In
      the third test, the AC frequency was changed to 30 Hz with the subsequent change
      in Bdc to 1.97 microT to tune for H+ as in the first test. The Bac values ranged
      from 0.79 to 2.05 microT rms. After a 23 h incubation and exposure to the MF in
      the presence of NGF (5 ng/ml), the NO was analyzed using a stereoscopic
      microscope. The results showed that the NGF stimulation of neurite outgrowth
      (NSNO) was affected by MF combinations over most of the Bac exposure range
      generally consistent with the predictions of the IPR model. However, for a
      distinct range of Bac where the IPR model predicted maximal ionic influence, the
      observed pattern of NSNO contrasted sharply with those predictions. The symmetry
      of this response suggests that values of Bac within this distinct range may
      trigger alternate or additional cellular mechanisms that lead to an apparent lack
      of response to the MF stimulus.

PMID- 8742752
TI  - Theoretical analysis of magnetic field interactions with aortic blood flow.
AB  - The flow of blood in the presence of a magnetic field gives rise to induced
      voltages in the major arteries of the central circulatory system. Under certain
      simplifying conditions, such as the assumption that the length of major arteries
      (e.g., the aorta) is infinite and that the vessel walls are not electrically
      conductive, the distribution of induced voltages and currents within these blood
      vessels can be calculated with reasonable precision. However, the propagation of
      magnetically induced voltages and currents from the aorta into neighboring tissue
      structures such as the sinuatrial node of the heart has not been previously
      determined by any experimental or theoretical technique. In the analysis
      presented in this paper, a solution of the complete Navier-Stokes equation was
      obtained by the finite element technique for blood flow through the ascending and
      descending aortic vessels in the presence of a uniform static magnetic field.
      Spatial distributions of the magnetically induced voltage and current were
      obtained for the aortic vessel and surrounding tissues under the assumption that
      the wall of the aorta is electrically conductive. Results are presented for the
      calculated values of magnetically induced voltages and current densities in the
      aorta and surrounding tissue structures, including the sinuatrial node, and for
      their field-strength dependence. In addition, an analysis is presented of
      magnetohydrodynamic interactions that lead to a small reduction of blood volume
      flow at high field levels above approximately 10 tesla (T). Quantitative results
      are presented on the offsetting effects of oppositely directed blood flows in the
      ascending and descending aortic segments, and a quantitative estimate is made of
      the effects of assuming an infinite vs. a finite length of the aortic vessel in
      calculating the magnetically induced voltage and current density distribution in
      tissue.

PMID- 8742753
TI  - Raman spectroscopic evidence for structural changes in poly-L-lysine induced by
      an approximately 50 mT static magnetic field.
AB  - We have explored the mechanism of coupling of an approximately 50 mT static
      magnetic field with the alpha helices of poly-L-lysine. Structural changes in
      poly-L-lysine were determined by Raman spectroscopy. Our testable hypothesis is
      that static magnetic fields of this magnitude can couple with the alpha-helical
      segments of the polypeptide, and, as a result, the structure of the polypeptide
      is significantly altered. Our model further suggests that a static magnetic field
      can promote protein unfolding and can prevent refolding.

PMID- 8742754
TI  - Absence of relation between sick leave caused by musculoskeletal disorders and
      exposure to magnetic fields in an aluminum plant.
AB  - This is a study of the relationship between occupational exposure to magnetic
      fields in pot rooms and occurrence of sick leave caused by musculoskeletal
      disorders. The average exposure to static magnetic fields was 8 mT in the pot
      rooms. Ripple fields were recorded as well. A cohort of 342 exposed workers and
      222 unexposed workers from the same electrolysis plant was retrospectively
      followed for 5 years. The reference group had a type of work similar to the
      exposed group except for the exposure to magnetic fields. The occurrence of sick
      leave and the diagnoses causing the sick leave were obtained from the
      Occupational Health Care Unit: these data were stored in their computer files.
      The data were complete. No relationship between the occurrence of sick leave
      caused by musculoskeletal disorders and exposure to magnetic fields was found.
      This was the case for both the annual number of periods of sick leave and the
      total number of days with sick leave. The results must be interpreted with
      caution due to limitations in the design and available data. Also, static
      magnetic fields constituted the major exposure, and the results may be different
      when related to work in other types of magnetic-field exposure.

PMID- 8742755
TI  - Effect of low-intensity millimeter wave electromagnetic radiation on regeneration
      of the sciatic nerve in rats.
AB  - The effect of low-intensity millimeter wave electromagnetic radiation (MWR) on
      regeneration of the rat sciatic nerve after transection and microsurgical
      reapproximation was examined. Rats were exposed to 54 GHz MWR at a power density
      of 4 mW/cm2. It was found that MWR treatment of the femoral skin in the area of
      suture accelerated the regeneration of nerve fibers. At the twentieth
      postoperative day, the MWR-treated animals had a 32% increase in the regeneration
      distance compared to the control animals. The conduction velocity showed a 26%
      increase in the MWR-treated animals.

PMID- 8742756
TI  - Cell culture dosimetry for low-frequency magnetic fields.
AB  - Calculations of the current density and electric field distributions induced in
      cell cultures by an applied low-frequency magnetic field have assumed that the
      medium is uniform. This paper calculates these distributions for a more
      realistic, inhomogeneous, anisotropic model in which the cells are regarded as
      conducting squares surrounded by insulating membranes. Separate parameters are
      used to specify the resistivities of the cell interior, the cell membrane
      parallel to its surface, the cell membrane perpendicular to its surface, and the
      intercellular junction parallel to the membrane. The presence of gap junctions
      connecting the interiors of adjacent cells is also considered. For vertical
      applied magnetic fields, the induced currents and field distributions may deviate
      considerably from the homogeneous medium model if there is sufficiently tight
      binding of the cells to each other. The presence of gap junctions can produce
      relatively large transmembrane electric fields or intracellular current
      densities. These considerations are generally less important for horizontal
      applied fields. A simple microscopic model of the cell surface is also discussed.

PMID- 8742757
TI  - Dynamic properties of Lednev's parametric resonance mechanism.
AB  - This paper presents a further development of the mechanism for the detection of
      weak magnetic fields proposed by [Lednev (1991): Bioelectromagnetics 12:71-75].
      The fraction of excited oscillator states of an unhydrated ion is studied in a
      dynamic model driven by the predicted (time-varying) transition probability in
      the presence of thermal noise and an unspecified excitation mechanism. The main
      results of Lednev are confirmed. In addition, I conclude that ultraharmonic and
      ultrasubharmonic resonances may also be observed, provided that the response time
      of the dynamic system is similar to the period of the oscillating magnetic field.
      I discuss the time scales involved in the mechanism and present theoretical
      constraints on these parameters. The crucial requirement for the theory's
      applicability is that the lifetime of the excited states of the affected ion
      oscillator exceeds the period of the applied magnetic field. Numerical solutions
      of the dynamic system are given and are shown to correspond well to theoretical
      expectations. The main discrepancy between the theories of Lednev and of
      Blanchard and Blackman [Blanchard and Blackman (1994): Bioelectromagnetics 15:217
      238] appears to be due to an inconsistency in the latter paper. The general
      problem of robust analysis of experimental data is discussed, and I suggest a
      test of compliance with the Lednev model that is independent of all parameters
      except for the ratio of oscillating and static field strength (B1/B0) for many
      resonance conditions and experimental models.

PMID- 8742758
TI  - Social networks in disease transmission: the Colorado Springs Study.

PMID- 8742759
TI  - Using dyadic data for a network analysis of HIV infection and risk behaviors
      among injecting drug users.

PMID- 8742760
TI  - Injecting drug use, characteristics of significant others, and HIV-risk
      behaviors.

PMID- 8742761
TI  - Sibling homophily in HIV infection: biopsychosocial linkages in an urban African
      American sample.

PMID- 8742762
TI  - Focal networks and HIV risk among African-American male intravenous drug users.

PMID- 8742763
TI  - A comparison of drug use networks across three cities.

PMID- 8742764
TI  - Ethical and legal issues in social network research: the real and the ideal.

PMID- 8742765
TI  - Network models for HIV outreach and prevention programs for drug users.

PMID- 8742766
TI  - A personal network approach to AIDS prevention: an experimental peer group
      intervention for street-injecting drug users: the SAFE study.

PMID- 8742767
TI  - Promising social network research results and suggestions for a research agenda.

PMID- 8742768
TI  - Medications and behavioral therapies: the whole may be greater than the sum of
      the parts.

PMID- 8742769
TI  - Enhancing the effectiveness of methadone using psychotherapeutic interventions.
AB  - There is consistent evidence that the efficacy of methadone can be enhanced by
      psychotherapeutic interventions. For individual psychotherapy, the increased
      efficacy is most demonstrable among methadone patients also suffering from
      psychiatric disorders. Patients with severe psychiatric problems generally show
      little response to drug counseling alone. There is no evidence of a consistent
      advantage of one type of psychotherapy over another. Contingency contracting
      using take-home doses of methadone to reinforce drug-free urines has been shown
      to be effective, at least over the short term. Rewarding clean urines by vouchers
      exchangeable for retail items is supported by a growing experimental database,
      although practical issues remain for publicly funded methadone programs. The use
      of methadone dose as a reinforcer has shown some efficacy, but there are both
      ethical and conceptual problems. Finally, while there are likely to be some
      benefits from simply administering methadone alone in the most economical way,
      the available evidence clearly shows that a relatively minor investment in
      counseling, individual psychotherapy, or contingency contracting can result in
      major improvements in the results of this medication.

PMID- 8742770
TI  - Integrating psychotherapy and pharmacotherapy for cocaine dependence: results
      from a randomized clinical trial.

PMID- 8742771
TI  - Can psychotherapy rescue naltrexone treatment of opioid addiction?

PMID- 8742772
TI  - Strategies to maximize the efficacy of naltrexone for alcohol dependence.

PMID- 8742773
TI  - Disulfiram (antabuse) contracts in treatment of alcoholism.
AB  - Although studies repeatedly demonstrate that alcoholics who consistently take
      disulfiram experience more favorable drinking outcomes, serious problems with
      compliance among the majority of alcoholic patients have reduced the
      effectiveness of disulfiram as a therapeutic adjunct. In general, alcoholism
      counseling with disulfiram simply prescribed seems no more effective than
      counseling without disulfiram (Fuller et al. 1986). Problems with compliance as
      well as problems with acceptance by patients and likely by clinical staff reduce
      the utility of disulfiram in the treatment of alcoholism. Implants, incentives,
      and various forms of observed or supervised disulfiram have been studied as
      possible solutions to the problems with compliance. Disulfiram implants appear
      largely ineffective due to failure to release adequate levels of disulfiram and
      risks of surgical complications and rejection. Newer techniques (see Allen and
      Litten 1992) may ultimately lead to a more effective implant. Incentives with
      personally relevant and obvious reinforcement value such as money, avoidance of
      incarceration, remaining employed, and continuation of methadone for opiate
      addicts, have been used effectively. Enhancement strategies with less tangible
      incentives also show promise. Among these are feedback on results of biochemical
      measures of disulfiram compliance and continuation in a familiar treatment
      program. Although each of the studies of incentives suffers from specific
      methodological limitations, the findings uniformly demonstrate better disulfiram
      compliance, less drinking, and better clinical outcomes for those who received a
      meaningful incentive for taking disulfiram. External monitoring of the patient
      taking disulfiram to assure compliance is typically used in studies evaluating
      incentives for taking the medication. Observed or supervised disulfiram in its
      own right and without tangible incentives also has received increasing attention
      as a method for enhancing compliance. Incorporation of such a strategy would seem
      to have potential for wide applicability in alcoholism treatment programs. Three
      forms of supervised disulfiram have been studied: (1) a written disulfiram
      contract, such as in BMT, with instructions about the benefits of the disulfiram
      contract and methods to establish disulfiram use as a daily habit and specifying
      that the alcoholic will take disulfiram daily while the spouse observes, that the
      couple will mutually thank each other, and that they will refrain from arguments
      or discussions about the alcoholic's drinking; (2) the disulfiram contract used
      in CRA, which is identical in form to the BMT contract except that talk about
      drinking is not prohibited; and (3) supervised disulfiram without a written
      contract, special instructions, or explicit verbal thanking. Studies of these
      three forms of observed disulfiram have been among the better controlled studies.
      Each approach has produced very promising results. A disulfiram contract with BMT
      produced less short-term drinking than disulfiram accompanied either by couples
      or individual counseling. Unfortunately, the superior BMT drinking results eroded
      because many couples discontinued their disulfiram contract after treatment ended
      (O'Farrell et al. 1985, 1992). Adding couples RP sessions after BMT led to better
      fulfillment of the disulfiram contract and better drinking and marital outcomes
      than BMT alone. These better RP outcomes persisted for 18 to 24 months after BMT
      for the entire sample and throughout the entire 30-month followup after BMT for
      those with more severe drinking and marital problems (O'Farrell et al. 1993).
      Thus, disulfiram contracts used with BMT are associated with less drinking and
      greater disulfiram compliance, while the specific contribution of disulfiram
      contracts to BMT remains to be investigated.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8742774
TI  - Combining behavioral therapy and pharmacotherapy for smoking cessation: an
      update.

PMID- 8742775
TI  - Integrating psychological and pharmacological treatment of dually diagnosed
      patients.

PMID- 8742776
TI  - Combining pharmacotherapy with psychotherapy for substance abusers with
      borderline personality disorder: strategies for enhancing compliance.
AB  - DBT is a comprehensive, behaviorally oriented treatment designed for highly
      dysfunctional individuals meeting criteria for BPD. Many of these criteria are
      characteristic of drug abusers, and some of the problems encountered in treatment
      of drug abusers, especially when various treatments are combined, are similar.
      The basic armamentarium of the DBT therapist is the balancing of validation and
      acceptance treatment strategies with problem-solving procedures, including
      contingency management, exposure-based procedures, cognitive modification, and
      skills training. In addition, a number of specific strategies have been woven
      together to enhance compliance and to reduce the staff splitting that is so
      frequent with this population. Those described in this chapter include orienting
      and commitment strategies and the focus in DBT on reducing therapy-interfering
      behavior and on consultation with the client rather than with the client's
      network.

PMID- 8742778
TI  - Some methodological comments.

PMID- 8742777
TI  - Integration of behavioral and pharmacological treatments for panic disorder:
      implications for the treatment of substance dependence.

PMID- 8742779
TI  - Targeting drugs to the brain by sequential metabolism.

PMID- 8742780
TI  - Action of opioid drugs on the brain-reward system.

PMID- 8742781
TI  - Drugs that modify opioid tolerance, physical dependence, and abstinence symptoms:
      preclinical and clinical studies.
AB  - In summary, the effects of drugs affecting the MTD and abstinence syndrome in
      mice, rats, monkeys, and humans have been described. Although mu opioid
      antagonists block tolerance and dependence on morphine, they also antagonize the
      analgesic response to morphine and, therefore, may not be useful clinically in
      inhibiting the MTD process. On the other hand, delta-selective opioid antagonists
      do not modify morphine analgesia but block the MTD process and, therefore, may
      have therapeutic potential. Neuropeptides like TRH, MIF, and cyclo (Leu-Gly)
      appear to produce similar results although their mechanism of action may be quite
      different. Cyclo (Leu-Gly) produces its action on oral administration and,
      therefore, further studies are warranted with this peptide. The CCKB receptor
      antagonist enhances morphine analgesia and blocks tolerance to morphine but has
      no effect on the development of dependence on morphine. EAA antagonists like MK
      801 block tolerance to the analgesic effect of morphine selectively but are quite
      toxic. Therefore, newer, less toxic agents like LY 274,614 need to be developed.

PMID- 8742782
TI  - Future directions in the pharmacological management of hyperalgesic and allodynic
      pain states: the NMDA receptor.

PMID- 8742783
TI  - Dual inhibitors of enkephalin-degrading enzymes (neutral endopeptidase 24.11 and
      aminopeptidase N) as potential new medications in the management of pain and
      opioid addiction.

PMID- 8742784
TI  - Enhanced N-methyl-D-aspartate (NMDA)-induced activity following morphine:
      sensitivity to sigma and PCP ligands.

PMID- 8742785
TI  - Dynorphin A: a rectifying peptide.

PMID- 8742786
TI  - Inhibitors of nitric oxide synthase and the opioid withdrawal syndrome.
AB  - The NOS inhibitors L-NARG and L-NAME attenuate weight loss and wet dog shakes,
      two specific signs of opioid withdrawal in rats. NMMA is more potent than L-NAME,
      consistent with the in vivo actions of these compounds as inhibitors of NOS. In
      addition, NMMA antagonizes naloxone-induced jumping in morphine-dependent rats.
      The NOS inhibitors generally increase teeth chattering in precipitated
      withdrawal. The profile of the diminished withdrawal signs produced by these
      drugs differs from that produced by clonidine, which stimulates locomotor
      activity and does not increase teeth chattering in precipitated opioid withdrawal
      (Kimes et al. 1990). These findings suggest that administration of inhibitors of
      NOS may be an effective treatment of the opioid withdrawal syndrome alone or in
      combination with clonidine (U.S. patent #5,225,40).

PMID- 8742787
TI  - Nitric oxide and opioid tolerance.

PMID- 8742788
TI  - Methoclocinnamox: a mu partial agonist with pharmacotherapeutic potential for
      heroin abuse.

PMID- 8742789
TI  - ACEA-1011, a novel NMDA receptor/glycine site antagonist, produces
      antinociception but not tolerance in the formalin test in mice.

PMID- 8742790
TI  - Etorphine elicits unique inhibitory-agonist and excitatory-antagonist actions at
      opioid receptors on sensory neurons: new rationale for improved clinical
      analgesia and treatment of opiate addiction.

PMID- 8742791
TI  - The association of neuropathic pain, morphine tolerance and dependence, and the
      translocation of protein kinase C.
AB  - This series of studies has investigated the involvement of the NMDA receptor and
      the translocation of PKC in the seemingly unrelated phenomena of neuropathic pain
      and tolerance and dependence to narcotic analgesic drugs. This work has
      demonstrated that the NMDA receptor and PKC translocation are importantly
      involved in neuropathic pain and morphine tolerance or dependence and that these
      phenomena may be importantly interrelated. Neuropathic pain following nerve
      injury is a major chronic pain syndrome. Utilizing a rat model of painful
      peripheral mononeuropathy produced by CCI of the sciatic nerve, the authors have
      investigated central mechanisms of postinjury neuropathic pain. Behavioral and
      pharmacological studies indicate that thermal hyperalgesia and spontaneous pain
      behaviors observed in this model are attenuated by treatment with NMDA receptor
      antagonists. A consequence of NMDA receptor activation is calcium influx, which
      in turn can result in translocation of PKC from cytosol to membrane. Inhibitors
      of intracellular PKC translocation and activation block thermal hyperalgesia and
      spontaneous pain behaviors after CCI and also reduce the elevated spinal cord
      neural activity in CCI rats. Furthermore, spinal cord levels of membrane-bound
      PKC reliably increase in CCI rats as a result of translocation of PKC revealed by
      the [3H]PDBu autoradiographic assay. This increase in membrane-bound PKC is
      associated with postinjury neuropathic pain behaviors in CCI rats and both pain
      related behaviors and membrane-bound PKC are reduced potently by GM1 ganglioside.

PMID- 8742792
TI  - Classical hallucinogens: an introductory overview.

PMID- 8742793
TI  - Are hallucinogens psychoheuristic?
AB  - The author argues in this chapter for a reconsideration of the perception of
      hallucinogens as being only toxic, damaging, and therefore strictly condemnable
      for being abused. The author advocates that hallucinogens be viewed as powerful
      psychoheuristic tools that, in combination with other necessary conceptual (such
      as holarchic theory) and laboratory tools (such as PET scan or MRI), may help
      solve a major mystery of nature: the workings of human brains and minds.

PMID- 8742794
TI  - Lysergamides revisited.

PMID- 8742795
TI  - Structure-activity relationships of the classic hallucinogens and their analogs.

PMID- 8742796
TI  - Human hallucinogenic drug research: regulatory, clinical, and scientific issues.

PMID- 8742797
TI  - Serotonin receptor involvement in an animal model of the acute effects of
      hallucinogens.

PMID- 8742798
TI  - The stimulus effects of serotonergic hallucinogens in animals.

PMID- 8742799
TI  - Electrophysiological studies on the actions of hallucinogenic drugs at 5-HT2
      receptors in rat brain.

PMID- 8742800
TI  - Neurochemical evidence that hallucinogenic drugs are 5-HT1c receptor agonists:
      what next?

PMID- 8742801
TI  - Autoradiographic approaches to studying hallucinogens or other drugs.
AB  - Autoradiography provides a powerful tool whereby an investigator can study
      different aspects of hallucinogens in the laboratory and the clinic. Receptor
      autoradiography can be performed in vitro to map binding sites of hallucinogens
      or to assess potential neurotoxic sequelae of hallucinogen treatments. Similarly,
      such studies can be performed in vivo to the same end. Receptor autoradiography
      can be performed in a clinical setting using PET to study acute dynamic binding
      properties of hallucinogens in humans or for long-term followup studies. In vivo
      autoradiography of metabolic markers appears useful in the laboratory and
      potentially in the clinic to help researchers understand not only where, but also
      the manner in which, the brain responds functionally to hallucinogens.

PMID- 8742802
TI  - Hallucinogens acting at 5-HT receptors: toward a mechanistic understanding at
      atomic resolution.

PMID- 8742803
TI  - Molecular modeling of the interaction of LSD and other hallucinogens with 5-HT2
      receptors.

PMID- 8742804
TI  - Structure and function of serotonin 5-HT2 receptors.

PMID- 8742805
TI  - Role for the mesocortical dopamine system in the motivating effects of cocaine.
AB  - The search for a neurobiological substrate for the stimulant and reinforcing
      properties of cocaine has focused for some time on a particular part of the
      forebrain, the mesocorticolimbic dopamine (DA) system. This mesocorticolimbic DA
      system innervates the region of the nucleus accumbens (NACC) (ventral striatum)
      in the anterior part of the basal forebrain and appears to play a critical role
      in mediating the acute reinforcing effects of cocaine and amphetamine. This
      chapter reviews the role of mesocorticolimbic DA in the reinforcing properties of
      psychomotor stimulants as measured by intravenous (IV) drug self-administration
      in rats. In addition, the primary neuropharmacological mechanism for cocaine
      reinforcement provides a rich substrate for studying nondopaminergic modulation
      of the reinforcing actions of cocaine.

PMID- 8742806
TI  - Dopamine, a common substrate for the rewarding effects of brain stimulation
      reward, cocaine, and morphine.

PMID- 8742807
TI  - Neurobehavioral pharmacology of cocaine: role for serotonin in its locomotor and
      discriminative stimulus effects.

PMID- 8742808
TI  - A review of the effects of dopaminergic agents in humans: implications for
      medication development.

PMID- 8742809
TI  - Use of rodent self-administration models to develop pharmacotherapies for cocaine
      abuse.

PMID- 8742810
TI  - Pharmacological and behavioral treatment of cocaine addiction: animal models.

PMID- 8742811
TI  - Preclinical assessment of cocaine antagonist drugs in squirrel monkeys.

PMID- 8742812
TI  - Cocaine self-administration research: treatment implications.

PMID- 8742813
TI  - Neurobiological mechanisms underlying the acquisition and expression of incentive
      motivation by cocaine-associated stimuli: relationship to craving.

PMID- 8742814
TI  - Cocaine reward and cocaine craving: the role of dopamine in perspective.

PMID- 8742815
TI  - Inheritance of polycystic kidney disease in Persian cats.
AB  - Polycystic kidney disease in Persian cats culminates in chronic renal failure
      after a variable clinical course. An affected 6-year-old Persian cat was used to
      establish a colony of cats with polycystic kidney disease. In affected cats,
      cysts could be detected by ultrasonography as early as 7 weeks of age. Absence of
      cysts on ultrasound examination at 6 months of age was correlated with absence of
      polycystic kidney disease at necropsy. Both males and females were affected and,
      of progeny from affected x unaffected crosses, 42% were affected and 58% were
      unaffected. In affected x affected crosses, 73% of progeny were affected and 27%
      were unaffected. These results are compatible with autosomal dominant inheritance
      of this trait. Polycystic kidney disease in Persian cats resembles autosomal
      dominant polycystic kidney disease (ADPKD) in human beings, and represents a
      valuable animal model of the human disease.

PMID- 8742816
TI  - RFLP mapping of expressed sequence tags in the chicken.
AB  - Chicken cDNA probes were used to map 10 loci by restriction fragment length
      polymorphism (RFLP) analysis in progeny of the Jungle Fowl x White Leghorn
      chicken backcross gene mapping reference population. The cDNA probes were from a
      subset of a T-cell library whose sequence tags showed significant homology to
      other avian or mammalian sequences in the EMBL database. Placement of loci
      generated by Compton cDNA clones on the East Lansing linkage map contributes to
      development of a consensus from the two linkage maps and will help provide a
      framework to evaluate the phenotypic effects of these genes.

PMID- 8742817
TI  - Genetic and physical mapping of the chicken IGF1 gene to chromosome 1 and
      conservation of synteny with other vertebrate genomes.
AB  - The chicken insulin-like growth factor 1 gene has been assigned to the short arm
      of chromosome 1 near the centromere by fluorescence in situ hybridization and
      genetic linkage analysis. Comparison of physical and genetic linkage maps locates
      the centromere between the IGF1 and GAPD loci. Comparison of the genetic maps of
      chicken and other vertebrates reveals a highly conserved syntenic group,
      including the GAPD-IGF1 loci.

PMID- 8742818
TI  - Canine genetic linkage study using heterologous DNA probes.
AB  - We have used clones of 17 single-copy human DNA sequences to analyze their
      counterparts in the genome of the domestic dog by heterologous hybridization. Ten
      of the 17 sequences represented anchor loci proposed for comparative mammalian
      mapping. Eight of 17 human clones (including three of the anchor loci) gave clear
      hybridization signals when used with Southern blots of canine DNA. Five of these
      eight (including two anchor loci) showed diallelic restriction fragment length
      polymorphisms in a large kindred of Brittany spaniels and could be used for
      segregation studies. Several probes chosen from different human chromosomes also
      were unlinked in the dog. By contrast, linkage was found between the canine
      counterparts of the closely linked human serum amyloid A gene family. Three
      markers linked on human chromosome II appeared not to be syntenic in the dog. DNA
      markers linked to various human genetic neuromuscular diseases were not linked to
      hereditary canine spinal muscular atrophy which segregates in this kindred.
      However, there was evidence of possible linkage of this disorder with a canine
      counterpart of the tyrosinase gene. Segregation studies using heterologous single
      copy DNA probes can be performed in dogs, but the level of inbreeding may reduce
      heterogeneity and limit the power of the analysis.

PMID- 8742820
TI  - Genetic regulation of border zone formation in female mastomys (Praomys coucha)
      adrenal cortex.
AB  - The unique border zone between the zona fasciculata and z. reticularis of the
      female adrenal cortex is formed in the wild-colored inbred mastomys (Praomys
      coucha) strain, MWC, but never in the chamois-colored inbred strain, MCC. This
      clear strain-specific trait was genetically analyzed using F1, F2, and backcross
      progenies produced between MWC and MCC. Reciprocal crosses gave no significant
      differences in the phenotypic ratio of F1 or F2 progeny. Border zone formation
      was detected in 0% of F1 females, 25.8% of F2 females, 0% of backcross females
      between F1 and MCC, and 47.7% of backcross females between F1 and MWC. From these
      results, it was concluded that border zone formation in the female MWC adrenal is
      regulated by a single autosomal recessive gene and this gene was named bzf
      (border zone formation).

PMID- 8742819
TI  - Tandem repeats and heteroplasmy in the mitochondrial DNA control region of the
      loggerhead shrike (Lanius ludovicianus).
AB  - We report the presence of a 128 bp tandem repeat in the mitochondrial control
      region of the loggerhead shrike (Aves: Lanius ludovicianus). All individuals
      examined had either two or three copies of the repeat or were heteroplasmic for
      two and three copies. This is the first direct demonstration of a tandem repeat
      associated with heteroplasmy in the control region of a bird. A novel model for
      repeat duplication, which involves an inverted repeat located adjacent to the
      tandemly repeated sequence, is presented. Individuals with three repeats are
      absent from the endangered population of San Clemente loggerhead shrike in
      southern California, suggesting that the island endemic has a small effective
      population size and that there is insignificant gene flow from the adjacent
      mainland.

PMID- 8742821
TI  - Genetic and environmental impacts on litter size and early infant survival in
      three species of callitrichids.
AB  - Callitrichids are unusual among anthropoid primates in that they can deliver one
      to four offspring per litter in captivity. Factors underlying intraspecific
      variation in litter size are unclear. Data from the Oak Ridge Associated
      Universities (ORAU) Marmoset Research Center provided an opportunity to
      investigate determinants of variation in (1) average litter size at birth and (2)
      average litter size surviving to 2 weeks of age in Saguinus fuscicollis, S.
      oedipus, and Callithrix jacchus. The objectives were to (1) investigate the
      impact of parity, husbandry, origin (wild or captive), and subspecific
      hybridization on phenotypic variance in litter size and (2) to estimate the
      heritability of litter size at birth and at 14 days. Husbandry changes were the
      only significant covariate and increased litter size at birth in C. jacchus only.
      Heritability estimates for average litter size at birth were significant only in
      S. fuscicollis (h2 = 0.306). Heritability of average litter size at 2 weeks of
      age was not significantly greater than zero. Estimates of genetic variability
      were relatively high, however both traits had very high levels of residual
      variance. The results suggest that litter size is a malleable trait that may
      respond to environmental factors.

PMID- 8742823
TI  - Tuberculosis notification update.

PMID- 8742822
TI  - DNA fingerprinting confirms isogenicity of androgenetically derived rainbow trout
      lines.
AB  - Homozygous and hybrid clonal lines of rainbow trout (Oncorhynchus mykiss) were
      confirmed to be isogenic using multilocus DNA fingerprinting. Homozygous clones
      were produced by androgenesis and gynogenesis using gametes from androgenetic
      male and female rainbow trout, respectively. Isogenic F1 hybrid lines were
      produced by crossing homozygous fish from different strains. One line of hybrid
      clones showed segregation for maternally inherited DNA fingerprint markers. The
      female from this cross, the only presumptive homozygous gynogenetic individual
      used in this study, was thought to have been produced by gynogenesis followed by
      blockage of the first cleavage division, but based on the DNA fingerprint
      analysis, apparently was derived by spontaneous polar body retention that
      maintained heterozygosity at some loci. Mutations at DNA fingerprint loci were
      not observed, indicating relative stability of fingerprint loci in the clonal
      lines. DNA fingerprinting appears to be a useful tool for identifying and
      genetically monitoring clonal lines of rainbow trout. Isogenic lines of rainbow
      trout will facilitate the production of saturated genetic maps for rainbow trout
      and enhance such endeavors as quantitative trait locus (QTL) analysis and loss of
      heterozygosity (LOH) studies in tumors.

PMID- 8742824
TI  - Sex-specific and hormone-controlled expression of a vitellogenin-encoding gene in
      the gypsy moth.
AB  - Microvitellogenin and vitellogenin cDNA from Manduca sexta (tobacco hornworm)
      were tested for use as molecular probes to investigate the expression of genes
      coding for vitellogenins in Spodoptera frugiperda (fall armyworm) and Lymantria
      dispar (gypsy moth). Cross-hybridization was not observed between the M. sexta
      cDNAs and S. frugiperda DNA and mRNA. Vitellogenin cDNA from M. sexta did not
      hybridize to L. dispar DNA or mRNA. However, the 834 bp microvitellogenin cDNA
      from M. sexta hybridized to an approximately 850 bp transcript in L. dispar mRNA.
      A 2.5 kb cDNA clone, pz64, was isolated from late last instar larvae of female L.
      dispar by differential screening. This clone has 38% amino acid sequence
      (deduced) and 55% nucleic acid sequence similarities with the 3'-end of high
      molecular weight vitellogenin in Bombyx mori (silkworm). When used as a probe in
      northern analysis of L. dispar mRNA, this cDNA hybridized to a 5.3 kb transcript
      in female last instar larvae, pupae, and adults, but not to male last instar
      larvae and adults. This cDNA did not hybridize to mRNA from M. sexta or S.
      frugiperda. Expression of the 5.3 kb vitellogenin transcript hybridizing to the
      2.5 kb cDNA clone was suppressed in 5-day-old last instar larvae of female L.
      dispar treated on day 2 with doses of the juvenile hormone analog, methoprene,
      greater than 10 nmol. Apparently, the high in vivo titer of juvenile hormone
      during the first 2 days of the last instar represses the transcription of
      vitellogenin mRNA.

PMID- 8742825
TI  - A new type of highly polymerized yolk protein from the cochineal insect
      Dactylopius confusus.
AB  - A female specific protein was isolated from eggs and female hemolymph of
      cochineal insects, using density gradient ultracentrifugation, ammonium sulfate
      precipitation, and size exclusion column chromatography. The protein was found to
      consist of four different subunits with apparent molecular weights (Mr) 45,000,
      49,000, 53,000, and 56,000, respectively. All four subunits were found to be
      glycosylated; no association of lipids was detected. Size exclusion column
      chromatography and non-denaturing polyacrylamide gel electrophoresis demonstrated
      that the native yolk protein exists as large polymers. Electron microscopy showed
      that these molecules are long, helical ribbons of variable size which are found
      in both hemolymph and eggs. Using cryo-electron microscopy, it was shown that the
      ribbons were 14.6 +/- 1.5 nm wide; the helix they form has a repeat distance of
      104.9 +/- 11.3 nm and a diameter of 42.1 +/- 5 nm. A clear substructure of the
      ribbons was recognized. The newly identified protein is the major yolk protein of
      Dactylopius confusus and no other proteins resembling the more familiar vitellins
      of other insect species were detected. Moreover, the D. confusus yolk protein
      appears to be unique both in its subunit structure and in its polymerizing
      qualities. Thus, the cochineal yolk protein (CYP) is suggested to represent a new
      type of insect yolk protein.

PMID- 8742826
TI  - Purification of adult Drosophila melanogaster lipophorin and its role in
      hydrocarbon transport.
AB  - Lipophorin was isolated from homogenized adult Drosophila melanogaster. It is
      stained by Sudan Black and has a native molecular mass of 640 kD and a density of
      1.12 g/ml. It consists of two glycosylated apoproteins of 240 and 75 kDa. Gas
      chromatography and mass spectrometry showed that lipophorins isolated separately
      from virgin 3-day-old male and female flies were associated with specific
      hydrocarbons, and that these were the same hydrocarbons found in male and female
      cuticles, respectively. Moreover, a pool of internal hydrocarbons was
      demonstrated for the first time, with chain lengths similar to those of the
      cuticular pool. Studies on the fate of the hydrocarbons synthesized de novo after
      topical applications of radiolabelled fatty acid precursors showed a decrease of
      the internal pool of hydrocarbons with time, concomitant with an increase of the
      cuticular pool. These results suggest that hydrocarbons synthesized at an
      internal site, possibly in oenocytes, may be transported to the cuticle of the
      flies by lipophorin.

PMID- 8742827
TI  - Adult specific expression and induction of cytochrome P450lpr in house flies.
AB  - Cytochrome P450lpr is a xenobiotic metabolizing P450 that is found in house flies
      (Musca domestica). To better understand the regulation of cytochrome P450lpr, the
      effects of 21 potential monooxygenase inducers were examined for their ability to
      induce total cytochromes P450 and cytochrome P450lpr levels in adult flies. Six
      compounds caused induction of total cytochromes P450 per mg protein in adult
      susceptible (CS) house flies: ethanol (1.6-fold), phenobarbital in food (1.5
      fold) or water (1.5-fold), naphthalene (1.3-fold), DDT (1.3-fold), xanthotoxin
      (1.4-fold), and alpha-pinene (1.2-fold). Six compounds were found to be inducers
      of cytochrome P450lpr: piperonyl butoxide in food (1.9-fold), phenobarbital in
      food (1.4-fold) and water (3.4-fold), clofibrate (1.3-fold), xanthotoxin (1.3
      fold), methohexital (1.3-fold), and isosafrole (1.3-fold). Comparison of our
      results with house fly P450 6A1 indicates that there are specific inducers for
      each of these individual P450s as well as compounds that induce both P450s. Total
      P450s were inducible by PB in CS house fly larvae, but not in LPR larvae.
      Immunoblotting revealed no detectable P450lpr in control or PB-treated larvae in
      either strain. Thus, although total P450s are inducible in the susceptible strain
      larvae, P450lpr does not appear to be normally present or inducible with PB in
      larvae of either strain. Northern blots of phenobarbital (in water) treated CS
      flies indicated that there was a 4.2-fold increase in the P450lpr (i.e., CYP6D1)
      mRNA levels over the untreated flies. In the multiresistant LPR strain there was
      no apparent induction of CYP6D1 mRNA by phenobarbital. Following phenobarbital
      induction, the level of CYP6D1 mRNA in the CS strain was about half of the level
      in the LPR strain.

PMID- 8742828
TI  - Synthesis of sn-1,2-diacylglycerols by monoacylglycerol acyltransferase from
      Manduca sexta fat body.
AB  - The pathway for the synthesis of sn-1,2-diacylglycerol stimulated by the action
      of adipokinetic hormone (AKH) in the insect fat body is unknown. Previous results
      from this laboratory suggested that the hydrolysis of stored triacylglycerol to
      sn-2-monoacylglycerol followed by the stereospecific acylation of sn-2
      monoacylglycerol catalyzed by a monoacylglycerol-acyltransferase (MGAT) could be
      the major route of AKH-stimulated sn-1,2-diacylglycerol synthesis. Thus, MGAT
      might represent a key enzyme of this pathway. In this study we characterized the
      MGAT activity from the Manduca sexta fat body. The activity, which was assayed by
      acylation of 2-monoolein using radioactive labeled palmitoyl-CoA, was found to be
      primarily a microsomal enzyme. The products of the acylation of 2-monoolein were
      1,2-diacylglycerol (40-50%), 1,3-diacylglycerol (20-30%), and triacylglycerol (30
      40%). The presence of triacylglycerol as a product revealed the presence of
      diacylglycerol-acyltransferase activity in the fat body microsomes. The pH
      optimum of MGAT activity was 7.0, and the dependence of the activity on the
      concentration of 2-monoolein showed saturation kinetics. An endogenous MGAT
      activity, which represented 20% of the maximal activity observed with added
      substrate, was detected. Optimal concentrations of palmitoyl-CoA ranged between
      0.10-0.20 mM. The specific activity of MGAT, measured under optimal conditions,
      was about 0.6 nmol DG formed/min-mg protein. MGAT activity was greatest with 2
      monoolein, and lower activity was observed when a saturated 2-monoacylglycerol
      was employed. The activity observed with sn-1-monoacylglycerol was lower than
      that observed with sn-2-monoacylglycerol. AKH did not stimulate MGAT activity,
      suggesting that either the enzyme is not under hormonal regulation or the
      monoacylglycerol pathway is not involved in the AKH-stimulated production of sn
      1,2-diacylglycerol in the M. sexta fat body.

PMID- 8742829
TI  - Invertebrate versus vertebrate neurogenesis: variations on the same theme?

PMID- 8742830
TI  - Screen for mutations affecting development of Zebrafish neural crest.
AB  - The neural crest provides a useful model to learn how cell fate diversification
      is regulated during vertebrate development. Our approach is to isolate zebrafish
      mutations in which the development of neural crest derivatives is disrupted, in
      order to learn about the underlying genetic mechanisms. We describe a screen in
      which parthenogenetic diploid embryos are examined both for visible phenotypes
      and for cellular defects in neural crest-derived sensory neurons recognized
      immunohistochemically. We present preliminary results from this screen and
      briefly describe a few representative mutations. We also discuss the general
      utility of our strategy and comment on the future directions of this approach.

PMID- 8742831
TI  - Regulatory interactions during early neurogenesis in Drosophila.
AB  - During neurogenesis in Drosophila, ectodermal cells are endowed with the capacity
      to become neuronal precursors. Following their selection, these cells initiate
      neuronal lineage development and differentiation. The processes of neuronal
      precursor specification and neuronal lineage development require the activities
      of several groups of genes functioning in a complex, hierarchical regulatory
      network. Whereas the proneural genes promote neurogenic potential, neurogenic
      genes restrict the acquisition of this identity to a subset of ectodermal cells.
      Following their selection, these cells express the pan neural neuronal precursor
      genes and a set of neuronal lineage identity genes. While lineage identity genes
      allow the various lineages to acquire specific identities, neuronal precursor
      genes presumably regulate functional and developmental characteristics common to
      all neuronal precursor cells.

PMID- 8742832
TI  - Control of cell fate choices by lateral signaling in the adult peripheral nervous
      system of Drosophila melanogaster.
AB  - The thoracic integument of the adult fruit fly is a relatively simple but highly
      patterned structure. It is composed of sensory organ cells distributed within a
      monolayer of epidermal cells. Both cell types are easily detected at the
      cuticular surface, as each external sense organ forms a sensory bristle and each
      epidermal cell secretes a small nonsensory hair. Inhibitory cell-cell
      interactions play a key role in regulating the distribution as well as the
      formation of the sense organs. This review focuses on the role of these cell-cell
      interactions in the adoption of alternative cell fates. We also show that Notch,
      Hairless, and Suppressor of Hairless, three components of this intercellular
      signaling pathway, exhibit dose-dependent genetic interactions. Finally we
      address how this intercellular signaling mechanism may be modulated to result in
      highly reproducible outcomes.

PMID- 8742833
TI  - Development and function of embryonic central nervous system glial cells in
      Drosophila.
AB  - Each abdominal neuromere of a Drosophila embryo contains about 60 glial cells
      [Klambt C, Goodman CS (1991): Glia 4:205-213; Ito et al. (1995): Roux's Arch Dev
      Biol, 204:284-307]. Among these, the midline and longitudinal glia are described
      to some detail. The midline glia are located dorsally in the nerve cord
      ensheathing the two segmental commissures. They are required for the proper
      establishment of commissures. The longitudinal glia, the A and B glia, and the
      segment boundary cells (SBC) are covering the longitudinal connectives. The
      longitudinal glia prefigure longitudinal axon paths and appear capable of
      regulating the expression of neuronal antigens. In the following we summarize the
      knowledge on the function of these glial cells.

PMID- 8742834
TI  - Cell lineage analysis of the Drosophila peripheral nervous system.
AB  - The peripheral nervous system (PNS) of Drosophila provides a very well
      characterized model system for studying the genes involved in basic processes of
      neurogenesis. Because of its simplicity and stereotyped pattern, each cell of the
      PNS can be individually identified and the phenotypic consequences of mutations
      can be studied in detail. Thus, some of the genetic mechanisms leading to the
      formation of type I sensory organs, the external, bristle-type sensory organs
      (es), and the internal, stretch-receptive chordotonal organs (ch) have been
      elucidated. Each sensory organ seems to be generated by a stereotyped pattern of
      cell division of individual ectodermal precursor cells. Recent advances in cell
      lineage analysis of the PNS have provided a detailed picture of almost all the
      lineages in the PNS, including those giving rise to the type II sensory neurons,
      also known as multiple dendritic (md) neurons. This knowledge will be
      instrumental in the precise characterization of the phenotypes associated with
      mutations in known and new genes and their interactions which determine cell fate
      decisions during neurogenesis. Here, we describe and compare three recently
      developed methods by which cell lineages have been assessed: single cell
      transplantation, bromodeoxyuridine (BrdU) incorporation studies, and the flp/FRT
      recombinase system from yeast. In the light of a more complete knowledge of the
      PNS lineages, we will discuss the effects of known mutations that alter neuronal
      cell fates.

PMID- 8742835
TI  - Role of environmental signals and transcriptional regulators in neural crest
      development.
AB  - The processes by which undifferentiated cells are assigned to particular fates
      are far from clear. We review recent work that has examined this problem in the
      neural crest, a multipotential cell population that gives rise to peripheral
      neurons in vertebrates. Peripheral neuronal differentiation appears to occur in a
      series of developmental steps that can be regulated independently by signals in
      the environment. Furthermore, such steps are reflected by corresponding changes
      in the pattern of regulatory transcription factor expression in differentiating
      neural crest cells. The determination of neuronal identity may proceed by a
      series of parallel regulatory pathways involving transcription factors acting
      both in cascades and in combinatorial arrays.

PMID- 8742836
TI  - Cell fate specification and differentiation in the nervous system of
      Caenorhabditis elegans.
AB  - Neuronal cell fates are specified by a hierarchy of events mediated by cell
      intrinsic determinants and cell-cell interactions. The determination of cell fate
      can be subdivided into three general steps. First, cell fate is restricted by the
      cell's position in the animal. For example, neurons are specified along the
      anterior-posterior body axis through the action of the Hox genes lin-39, mab-5,
      and egl-5. Second, a decision is made to generate a particular cell type, such as
      the progenitor of a neurogenic lineage as opposed to that of an epidermal
      lineage. Among the genes that influence this decision is the proneural gene lin
      32. Third, characteristics of a particular cell type are specified. For example,
      in a neurogenic lineage, a decision may be made to generate a specific neuron
      type such as a sensory or motor neuron. Genes that affect neuronal fate can act
      in different ways to influence the development of different types of neurons.

PMID- 8742837
TI  - Retinoblastoma gene in mouse neural development.
AB  - The retinoblastoma gene (Rb) was the first tumor suppressor gene to be cloned
      [Dryja et al., 1986; Friend et al., 1986; Lee et al., 1987], and, as a
      consequence, has been studied intensively within the context of cell cycle
      regulation and oncogenesis. However, a number of recent findings indicate that
      the retinoblastoma gene product (pRb) likely plays an essential role not only in
      controlling entry into the cell cycle, but also in the terminal differentiation
      of a number of different cell types [Lee et al., 1994; Gu et al., 1993]. In
      particular, the phenotype of the Rb nullizygous mice, created by a number of
      groups using homologous recombination [Jacks et al., 1992: Clarke et al., 1992;
      Lee et al., 1992], indicates that pRb is essential for normal development of the
      nervous and hematopoietic systems and may even function to regulate apoptosis
      [Haas-Kogan et al., 1995]. Although this paper briefly reviews the traditional
      role of pRB in regulation of cellular proliferation, we focus on the role of pRB
      in neuronal development and apoptosis. Recent reviews have been published on the
      role of pRb in cell cycle and transcriptional regulation [Hamel et al., 1992;
      Cobrinik et al., 1992; Kouzarides, 1993; Hollingsworth et al., 1993; Helin and
      Harlow, 1993; Sherr, 1994], as well as the relationship between pRb and p53
      [Picksley and Lane, 1994; White, 1994].

PMID- 8742838
TI  - Molecular modeling of transition metal complexes with nucleic acids and their
      constituents.

PMID- 8742839
TI  - Zinc complexes as targeting agents for nucleic acids.

PMID- 8742840
TI  - Metallocene interactions with DNA and DNA-processing enzymes.

PMID- 8742841
TI  - Evidences for a catalytic activity of the DNA double helix in the reaction
      between DNA, platinum(II), and intercalators.

PMID- 8742843
TI  - Metal ions in multiple-stranded DNA.

PMID- 8742842
TI  - Trans-diammineplatinum(II): what makes it different from cis-DDP? Coordination
      chemistry of a neglected relative of cisplatin and its interaction with nucleic
      acids.
AB  - The question raised, i.e., "trans-diammineplatinum(II)--what makes it different
      from its cis isomer?" permits a number of answers, relating to various aspects of
      the chemistry of the two compounds, but the crucial one concerning antitumor
      activity is yet to be answered. In principle, any of the following reasons or
      combinations thereof might account for the observed differences in biological
      effects, but some are more likely than others: 1. TARGET MOLECULES: It is
      generally accepted that DNA is the most important target molecule of cisplatin
      and that inhibition of DNA synthesis correlates with antitumor activity. This
      fact does not contradict observations on extensive reaction with other
      biomolecules. The mutagenic effects of trans-a2Pt(II), although weaker than for
      cis-DDP, point toward DNA as being an important target for trans-DDP as well. 2.
      DNA ADDUCTS: As a consequence of the inherent difference in geometry, the two
      isomers form different adducts. Specifically, trans-DDP cannot form 1,2
      intrastrand crosslinks, which represent by far the most abundant adducts of cis
      DDP. On the other hand, the trans isomer displays a greater variation in
      nucleobase donor sites (cf. Sec. 4.2). 3. DNA STABILITY: While the 1,2
      intrastrand adducts of cis-DDP, regardless if GG or AG, consistently cause DNA
      kinking and lead to thermal destabilization, the effects of trans-DDP adducts
      seem to be of a greater variability, causing thermal stabilization or
      destabilization. For intrastrand 1,3 adducts in puXpu sequences, the intervening
      base X appears to be important in this respect (cf. Sec. 4.3). 4. DNA REPAIR: In
      living cells, higher doses of trans-DDP as compared to cis-DDP are required to
      bind an equal number of Pt atoms per nucleotide [66]. On the other hand,
      bifunctional DNA adducts of either isomer inhibit DNA replication to the same
      extent [66,150,151]. This finding has been interpreted in terms of a differential
      repair of adducts of the two isomers [66], but an alternative explanation has
      also been offered [152]. It is to be noted that repair of monofunctional trans
      DDP lesions does not require enzymatic repair but rather may be accomplished by
      any nucleophile within the cell exercising a reasonably high trans influence,
      e.g., an S-donor of glutathione. 5. INTRINSIC REACTIVITY: Differences in
      hydrolysis kinetics of the two isomers (unfavorable equilibrium concentration of
      trans-[(NH3)2Pt-Cl(OH2)]+ [37]) and in reaction rates of various hydrolysis
      species with DNA constituents [36] could, in principle, explain a difference in
      biological effects. On the other hand, the kinetics of reactions of the dichloro
      species of both isomers with DNA (in the absence of any repair agents) appear not
      to be that largely different to produce a strong point for differential
      reactivity of this species. Model studies have shown at least one more distinct
      difference between mono(nucleobase) adducts of both isomers: While cis-[a2PtLCl]+
      can lose the amine trans to Cl, in trans-[a2PtLCl]+ Cl is capable of displaying L
      (cf. Sec. 6.1). Both reactions are not very fast with Cl-, but any good
      nucleophile replacing Cl- would do so with high efficiency. In the case of trans
      DDP, such a reaction leads to removal of Pt from DNA, unlike in the case of cis
      DDP (even though we are aware that cis effects may also be operative). With
      respect to amine displacement from monoadducts of cis-DDP, it is interesting to
      speculate on the fate of (toxic) NH3. Is it capable of undergoing condensation
      reactions with biomolecules? In theory, such a scenario might provide
      possibilities for the role of the amine ligands in cis-(amine)2Pt(II) compounds
      alternative to those commonly accepted (e.g., role of NH protons in stabilizing
      DNA adducts [153]). 6. TRANSPORT AND DISTRIBUTION: Despite differences in water
      solubility of the two isomers (trans-DDP less soluble), this property is unlikely
      to be important at physiological concentrations...

PMID- 8742844
TI  - DNA interactions with substitution-inert transition metal ion complexes.

PMID- 8742845
TI  - Effect of metal ions on the fluorescence of dyes bound to DNA.

PMID- 8742846
TI  - Photolytic covalent binding of metal complexes to DNA.

PMID- 8742847
TI  - Electrochemically activated nucleic acid oxidation.

PMID- 8742848
TI  - Electron transfer between metal complexes bound to DNA: is DNA a wire?

PMID- 8742849
TI  - Porphyrin and metalloporphyrin interactions with nucleic acids.

PMID- 8742850
TI  - Selective DNA cleavage by metalloporphyrin derivatives.

PMID- 8742851
TI  - Synthetic metallopeptides as probes of protein-DNA interactions.

PMID- 8742853
TI  - Nucleic acid chemistry of the cuprous complexes of 1,10-phenanthroline and
      derivatives.

PMID- 8742852
TI  - Targeting of nucleic acids by iron complexes.

PMID- 8742854
TI  - Specific DNA cleavage by manganese(III) complexes.

PMID- 8742855
TI  - Nickel complexes as probes of guanine sites in nucleic acid folding.

PMID- 8742856
TI  - Hydrolytic cleavage of RNA catalyzed by metal ion complexes.

PMID- 8742857
TI  - RNA recognition and cleavage by iron(II)-bleomycin.

PMID- 8742858
TI  - Metallobleomycin-DNA interactions: structures and reactions related to bleomycin
      induced DNA damage.

PMID- 8742859
TI  - Eating attitudes and body shape perceptions among elite rowers: effects of age,
      gender and weight category.
AB  - This study examined the influence of age, gender and weight category upon
      measures associated with eating disorders. Elite rowers (N = 124) participating
      in the 1994 Great Britain National Squad trials, completed the Eating Attitude
      Test (EAT) and the Body Shape Questionnaire (BSQ). Subjects were grouped
      according to whether they competed in the Lightweight (Female: < 59 kg, N = 31;
      Male: < 72.5 kg, N = 31) or Heavyweight (Female: N = 31; Male: N = 31) category.
      Results revealed significantly higher EAT and BSQ scores among the Lightweight
      group, 16.2% of whom showed EAT scores above the threshold associated with eating
      disorders. Females showed significantly higher BSQ scores than males. The
      interaction effect was significant for BSQ, indicating a much greater increase in
      scores from heavyweight to lightweight for females than for males. EAT and BSQ
      scores were inversely correlated with age. These results suggest that the risk of
      eating disorders among elite rowers is mediated by age, gender and weight
      category.

PMID- 8742860
TI  - An injury profile of elite ironman competitors.
AB  - An injury questionnaire was administered to the 30 elite ironman competitors
      (mean age = 25.7 +/- 4.6 yrs) participating in a commercially sponsored seven
      race national series. Responses provided retrospective data from the preceding
      three years indicating the type, location, frequency, cause and severity of
      injuries sustained by ironmen, and associated these injuries with particular race
      components (run, swim, board, ski). Twenty self-reported questionnaires were
      returned for analysis that described a total of 67 injuries incurred by 19
      subjects. Results indicated the following: (i) the most frequently injured body
      parts were the knee (n = 18) and shoulder (n = 14) with the lower extremity
      accounting for 55% of all injuries reported; (ii) knee, shin and calf injuries
      had a significant association with the run component and upper extremity injuries
      had a significant association with the swim component; (iii) running was
      perceived to be the most injurious race component in terms of the frequency and
      severity of injury; (iv) overtraining was perceived to be the main cause of
      injury; (v) tendinitis was perceived to be the main type of injury; (vi) athletes
      adjusted their training mode to accommodate injury so that total training volume
      could be maintained; and (vii) injury did not result in withdrawal from
      competition. Further research investigating the techniques used in the ironman
      event and their relationship to injury is recommended.

PMID- 8742861
TI  - A comparison of the injuries sustained by female basketball and netball players.
AB  - A prospective and reliable method of injury surveillance was implemented to
      document a comprehensive injury profile in female basketball and netball. The
      study further aimed to compare the injury profiles of the two sports. Trained
      observers viewed basketball and netball games, noting the occurrence of injuries.
      Injuries were confirmed by questioning all players on site after the game.
      Injured players completed a questionnaire and the progress of their injury was
      monitored by telephone interview. A total of 16,162 player participations were
      observed; 6,972 for basketball and 9,190 for netball. Comparable injury rates
      were observed for female basketball and netball players; 18.22 and 17.30 injuries
      per 1,000 participations, respectively. The ankle, hand and knee were the body
      parts injured most frequently in both sports, whilst head and neck injuries were
      prevalent in basketball only. Netball players sustained severe injuries at a rate
      3.3 times that of female basketball players. The major and severe injuries
      occurred at an average of one injury in 625 games in female basketball and one in
      250 games in netball. The ankle, knee and calf/shin were the body parts most
      frequently involved in the more serious injuries.

PMID- 8742862
TI  - Notational analysis on game strategy used by the world's top male squash players
      in international competition.
AB  - The purpose of this study was to provide a profile of the competition strategy
      used by the world's top squash players at the international level and provide
      recommendations for other players to improve their playing strategy. A total of
      10 matches including three in round one, the four quarter finals, the two semi
      finals, and the final of the 1993 Hong Kong Squash Open were filmed using a 3-CDD
      video camera. The tournament was played under the North American scoring system.
      Notational analysis which is based on frame by frame video analysis was used to
      categorize a player's motion. The frequency of each stroke, and the success or
      failure rate of each stroke were recorded. Shots were classified as "effective",
      "ineffective", "winning" and "losing" shots and the analysis demonstrated that
      70.28% were "effective", 19.86% were "ineffective", 5.37% were "winning" and
      4.48% were "losing" shots. The mean number of shots per game was 252.09. The
      order of priority using different kinds of strokes in matches were as follows:
      drive (length) (60.79%), drop (17.91%), volley (11.79%), boast (4.80%), and lob
      (4.72%). The results of this study show that the "pressure and attack game" was
      the most important strategy for the world's top squash players in producing
      winning performances. Also identified are the strokes and the strategies which
      should be practiced to improve performance. This method of notational analysis
      can be utilized to evaluate the strengths and weaknesses of players at all levels
      of competition.

PMID- 8742863
TI  - A test of Martens, Vealey and Burton's theory of competitive anxiety.
AB  - The purpose of this study was to test Martens, Vealey, and Burton's (1990)
      theoretical model of competitive anxiety. In order to assess the variables
      corresponding to the model, a sample of 199 (N = 126, male and N = 73, female)
      individual sport athletes completed the following inventories: the Sport Anxiety
      Scale (SAS; Smith, Smoll, & Schutz, 1990), items related to the uncertainty of
      outcome, items related to the importance of outcome, and the Competitive State
      Anxiety Inventory-2 (CSAI-2; Martens, Burton, Vealey, Bump, & Smith, 1990). In
      addition, the short-form of the Marlowe-Crowne Social Desirability Scale (M-C
      SDS; Reynolds, 1982) was completed by all subjects. The variables corresponding
      to the model underwent psychometric evaluation as well as a check for social
      desirability effects before they were used in a LISREL causal path model
      procedure. Results showed no concrete support for the basic propositions advanced
      through the model. Trait-anxiety did not significantly affect perception of
      threat and perception of threat had minimal effect on state-anxiety.
      Recommendations for future research are discussed.

PMID- 8742864
TI  - Attributions for recovery and adherence to sport injury rehabilitation.
AB  - The relations of causal attributions for recovery from knee surgery to recovery
      rate and rehabilitation adherence were examined in a sample of 34 recreational or
      competitive athletes. Subjects rated their open-ended attributions for recovery
      on the Revised Causal Dimension Scale (McAuley, Duncan, & Russell, 1992).
      Subjects who perceived themselves as recovering rapidly made more stable,
      personally controllable, and externally controllable attributions than subjects
      who perceived themselves as recovering slowly. Subjects designated by their
      physical therapist/athletic trainer (PT/AT) as recovering rapidly tended to
      attribute their rehabilitation progress to more internal and personally
      controllable factors than subjects identified as recovering slowly. Causal
      dimension ratings predicted PT/AT rehabilitation adherence ratings, but not
      attendance at rehabilitation sessions.

PMID- 8742865
TI  - Effects of oral creatine supplementation on multiple sprint cycle performance.
AB  - This study examined the influence of oral creatine monohydrate supplementation on
      repeated 10 s cycle ergometer sprint performance. Seventeen recreationally active
      males (mean +/- SD age, body mass, height, and peak oxygen uptake = 20.5 +/- 1.2
      yr, 72.1 +/- 10.3 kg, 176.8 +/- 6.6 cm and 3.87 +/- 0.91 l.min-1, respectively)
      participated in the 16 day experiment. All subjects initially completed a VO2peak
      test and were then administered glucose (4 x 10 g per day) in a single blind
      fashion for four days, after which they completed the first series of multiple
      sprints (7 x 10 s). Following the sprints, subjects were matched on sprint
      performance and divided into two groups (n = 8, placebo (Pl); and n = 9, creatine
      (Cr)). For the following four days, diets were supplemented with either Cr (4 x
      70 mg.kg-1 body mass per day mixed with 5 g glucose) or glucose (4 x 10 g per
      day); supplementation during this phase was double-blind. Subjects then repeated
      the multiple sprint and VO2peak tests. Measures of peak power output (PPO), mean
      power output (MPO), end-power output (EPO), and percent power decline were
      recorded during the sprints. Each 10 s sprint was separated by 30 s of passive
      recovery except for sprints five and six which were separated by five minutes.
      Venous blood was sampled at rest, immediately after sprint five, before sprint
      six, and following sprint seven for the analysis of plasma lactate and blood pH.
      Expired air was sampled for five minutes following sprint seven for the
      calculation of post-exercise VO2. Analysis of variance revealed that four days of
      Cr supplementation did not influence multiple sprint performance, plasma lactate,
      blood pH and excess post-sprint oxygen consumption. Furthermore, VO2peak was
      unchanged following Cr supplementation. The data suggest that either the four day
      period of Cr supplementation failed to significantly raise resting muscle [Cr],
      or that multiple sprint performance was not enhanced by increases in resting
      muscle [Cr].

PMID- 8742866
TI  - The origin and significance of secondary flows in the aortic arch.
AB  - This paper comprises a study of the secondary flow patterns that can develop in
      the human aortic arch. Clinical evidence of these secondary flows has been
      obtained by Kilner et al. using magnetic resonance velocity mapping techniques.
      Some of their results are presented for comparison in this paper. Four difference
      parametric models of the aortic arch have been analysed using computational fluid
      dynamic techniques. Both steady and transient flow conditions have been
      considered and two different commercially available software packages were used,
      namely FIDAP and FLOTRAN. A satisfactory comparison of the theoretical analysis
      with the results, both in vivo and in vitro, obtained by Kilner et al. for their
      out-of-plane inlet model was found. The theoretical analysis can now be extended
      to analyse the effect of different configurations and orientations of artificial
      aortic valves on the resulting aortic arch flow patterns.

PMID- 8742867
TI  - The application of an Actel field programmable gate array in the design of an ECG
      RR interval recorder.
AB  - Field Programmable Gate Arrays (FPGAs) allow digital circuitry to be integrated
      on to a single device without the long time penalty incurred with mask
      programmable Application Specific Integrated Circuits (ASICs). This makes FPGA
      technology an attractive option to engineer involved in designing digital
      circuitry where space is at a premium. Furthermore, the relatively low cost of
      FPGAs at low volume, compared to mask programmable ASICs make them an excellent
      prototyping option for designers who are considering low cost volume production
      with mask programmable ASICs. There are several different types of FPGAs
      available which thus creates confusion for prospective users uncertain of their
      relative benefits. This paper serves as an introduction to FPGA technology and
      the stages involved in implementing a design, via the application of an Actel
      FPGA to the development of an ambulatory long term electrocardiogram (ECG) based
      RR interval recorder.

PMID- 8742868
TI  - The application of engineering and technology in the management of diabetes.
AB  - Diabetes mellitus is a relatively common disorder in which many of the body's
      systems are affected, resulting in morbidity and mortality. Early diagnosis and
      good blood glucose control can delay or prevent the onset of these complications.
      This review illustrates how engineering and technology can help to achieve these
      goals.

PMID- 8742869
TI  - Scheduled inspection of electromedical equipment. Planning and assessment.
AB  - Scheduled inspections help ensure the safety and efficacy of medical equipment.
      To ensure the regular checking of all items we developed a practical and
      realizable protocol consisting of basic safety and functional tests. Non
      productive time spent searching for equipment was reduced enlisting the help of
      ward staff. Record keeping was simplified using monthly checklists detailing the
      tests to be performed. Clear labels distinguished items checked and the ward was
      informed about missing items. The effectiveness of the programme was assessed by
      auditing the number of items due for inspection, the average time per inspection,
      the number of faults found, and the incidence of breakdown repairs. The average
      inspection time per item was reduced to half an hour and the number of items due
      for inspection to below 10%. The programme was effective in fault detection (7%
      of items checked) and the incidence of breakdown repairs decreased from 75 to
      53%.

PMID- 8742870
TI  - Interposition arthroplasty of the elbow with rheumatoid arthritis.
AB  - Radiographic bone loss and clinical outcome were evaluated at a median of 6 years
      after interposition arthroplasty was performed in 35 elbows with rheumatoid
      arthritis. Seven early postoperative complications, two major and five minor,
      occurred. Three elbows subsequently required total elbow replacement. Clinical
      results were good in terms of pain relief but only fair in terms of joint
      mobility and stability. Radiographic elbow destruction progressed to a higher
      Larsen stage in half of the elbows. Measurements revealed humeral bone loss in
      two thirds of the elbows and ulnar bone loss in one third. In comparison with
      total elbow replacement, the long-term results of interposition arthroplasty were
      found to be inferior, with a total elbow replacement being required in one tenth
      of the elbows in the long term. In addition, bone loss often became extensive,
      making reoperation difficult or impossible. The authors recommend total elbow
      replacement as the first choice in the surgical treatment of the painful elbow
      with rheumatoid arthritis and cartilage destruction.

PMID- 8742871
TI  - Late complications in elbow arthroplasty.
AB  - The world literature (1986 to 92) reports an amazingly high complication rate of
      elbow arthroplasty, amounting to 43%. Accordingly, we also find a high revision
      rate (18% on average) and a considerable rate (15%) of permanent complications.
      These figures do not correspond to our own experience with the GSB III
      (Gschwend/Scheier/Bahler) elbow prosthesis, a sloppy hinge with flanges on the
      lower and anterior part of the distal humerus. Our respective figures of
      complications are two to four times lower for rheumatoid elbows. When
      complications are discussed, a clear distinction of the type of prosthesis is
      mandatory, because linked or nonlinked and nonconstrained or semiconstrained
      prostheses have specific complications. The following complications are discussed
      separately: loosening (radiologic and clinical), ulnar neuropathy, infection,
      dislocation and subluxation, uncoupling, intraoperative bone fractures, and
      failure of the implant. The possible causes are analyzed, and means to avoid or
      treat these complications are discussed. We conclude that even in the long term (
      > 10 years), results obtained with elbow arthroplasty are approaching those of
      hip and knee arthroplasty.

PMID- 8742872
TI  - Fixation strength of the ulnar component of total elbow replacement.
AB  - After clinical failure of ulnar component fixation by olecranon fracture
      occurred, this study examined different component designs to find the strongest
      type. Components requiring square cuts or rounded cuts to prepare the proximal
      ulna with short or long stems of polyethylene or metal were implanted in paired
      cadaver bones and tested to failure. Loads were applied through the articular
      surface in an anterior-posterior direction, causing bending fracture of the
      olecranon. The main findings were a higher strength if the bone was prepared to
      take a rounded rather than a square-shaped prosthesis body, a slightly higher
      strength with a metal component compared with a similarly shaped polyethylene
      component, and slightly less strength if a longer stem was used. We recommend the
      use of a polyethylene component with a rounded shape and short stem, because it
      will be thinner, entailing less bone excavation. Additionally, it is less costly
      than a metal-backed design.

PMID- 8742873
TI  - Lateral collateral ligament of the elbow joint: anatomy and kinematics.
AB  - The structure and kinematics of the lateral collateral ligament of the elbow
      joint were investigated in 10 cadaveric specimens. The lateral collateral
      ligament was observed to be a distinct part of the lateral collateral ligament
      complex. It contains posterior fibers that pass through the annular ligament and
      insert on the ulna. Three-dimensional kinematic measurements in different forearm
      rotations showed that joint puncture induced a 1 degree joint laxity significant
      in forced varus from 30 degrees to 80 degrees of flexion and in forced external
      rotation from 30 degrees to 120 degrees of flexion. Division of the
      posterolateral capsule caused no further laxity. Cutting the lateral collateral
      ligament induced a maximum laxity of 11.8 degrees at 110 degrees of flexion in
      forced varus and a maximum laxity of 20.6 degrees at 110 degrees of flexion in
      forced external rotation. The corresponding maximal posterior radial head
      translation was observed at 80 degrees to 100 degrees of flexion and was 5.7 mm
      in forced varus and 8.1 mm in forced external rotation. This study suggests the
      lateral collateral ligament to be an important stabilizer of the humeroulnar
      joint and the radial head in forced varus and external rotation. The humeroulnar
      stability is independent of forearm rotation.

PMID- 8742874
TI  - Radial head and neck fractures: anatomic guidelines for proper placement of
      internal fixation.
AB  - A cadaveric study of the radial head and neck was performed to determine the
      anterior and posterior limits for safe placement of internal fixation on the
      surface of the radial head or neck. A "safe zone" of approximately 110 degrees of
      radial head surface was first identified by cross-sectional anatomic dissections.
      This "safe zone" was then reproducibly confirmed relative to forearm position
      when viewed from a standard lateral approach. Because the proximal radioulnar
      joint cannot be directly visualized through the standard lateral approach, the
      zone was indirectly identified by making reference marks along the radial head
      and neck. To determine the position of the "safe zone" reference marks are first
      made along radial head and neck so as to bisect the bone's anteroposterior
      distance. Three such marks are made with the forearm in neutral rotation, full
      supination, and full pronation. Next, the posterior limit of the zone is
      determined by bisecting the reference marks made with the forearm in neutral
      rotation and full pronation. The anterior limit is determined by going nearly two
      thirds of the distance from the neutral mark to that mark made in full
      supination.

PMID- 8742875
TI  - Comparative electromyographic analysis of shoulder muscles during planar motions:
      anterior glenohumeral instability versus normal.
AB  - This study compared the electromyographic activity of rotator cuff and scapular
      muscles between subjects with anterior instability and subjects with normal
      shoulders. Thirty-eight patients were studied; 23 had anterior instability that
      was subsequently surgically confirmed, and 15 had normal shoulders. Fine wire
      electrodes were inserted into the subscapularis (upper and lower portions),
      supraspinatus, infraspinatus, rhomboid, serratus anterior, and trapezius (upper
      and lower portions) muscles. Abduction, scapular plane abduction (scaption), and
      forward flexion were performed over the range of motion and later divided into 30
      degrees intervals. In both abduction and scaption, the supraspinatus demonstrated
      significantly less electromyographic activity from 30 degrees to 60 degrees in
      shoulders with anterior instability compared with normal shoulders (p < 0.05).
      During all three motions, shoulders with anterior instability demonstrated
      significantly less electromyographic activity in the serratus anterior when
      compared with normal shoulders (p < 0.05). This occurred at 30 degrees to 120
      degrees of abduction and at 0 degree to 120 degrees of scaption and forward
      flexion. None of the other muscles demonstrated significant differences. These
      differences during planar motions were similar to those demonstrated during
      challenging overhead sport motions. Early rehabilitation efforts should focus
      both on the rotator cuff and scapular muscles to establish smooth, coordinated
      shoulder motion.

PMID- 8742876
TI  - Cinearthrography of the Bankart lesion and anterior capsule elongation.
AB  - Diagnostic cinearthrography was performed on 3368 patients with shoulder pain
      during the period of 1982 through 1992. Cinearthrography identified a Bankart
      lesion in 128 shoulders on which surgical stabilization was performed for
      recurrent anterior dislocation. The operative pathologic condition for each of
      these patients was correlated and analyzed with the measurements of the Bankart
      lesion identified on the cinearthrogram. A small Bankart lesion was seen in
      patients with anterior capsular elongation. A larger Bankart lesion was observed
      in patients who did not have anterior capsular elongation. Preoperative
      measurement of anterior capsular elongation has been difficult. An 80%
      probability existed that the presence and extent of a Bankart lesion identified
      on a cinearthrogram could be an indicator for the presence of anterior capsular
      elongation. Preoperative determination of anterior capsular elongation could be
      useful in selection of the optimum surgical procedure to correct recurrent
      anterior shoulder dislocations.

PMID- 8742877
TI  - Histologic and scanning electron microscopic study of the glenoid labrum.
AB  - Three-dimensional fibrillar architecture of the glenoid labrum and its attachment
      to the glenoid rim were studied in 15 cadaveric shoulders to understand the
      pathophysiologic condition of various shoulder diseases. The true anatomic labrum
      was a narrow band located at the junction of the glenoid rim and fibrous capsule
      and varied considerably in size and shape. A triple-layered collagen structure of
      the labrum was observed by scanning electron microscopy. The thin superficial
      layer (articular surface) was a reticulated fibrillar network. The second layer
      was stratified. These two layers seem to act as a bumper against impact on the
      humeral head. The third, main layer of the labrum consisted of bundles of the
      fine fibrils densely arranged almost parallel to each other and oblique to the
      glenoid rim. This layer appears to act as a cushion to stabilize the shoulder
      joint.

PMID- 8742878
TI  - Mechanoreceptors and reflex arc in the feline shoulder.
AB  - A reflex arc from the glenohumeral capsule to the biceps, infraspinatus,
      supraspinatus, and subscapular muscles was shown in a feline preparation.
      Branches of the suprascapular and subscapular nerves terminating in the capsule
      were identified and then stimulated with a 100 microseconds supramaximal pulse at
      10 pulses per second. Stimulation of the suprascapular articular nerve elicited
      electromyographic discharge in the biceps and infraspinatus muscles, whereas
      stimulation of the subscapular articular nerve elicited electromyographic
      discharge in the biceps, subscapularis, infraspinatus, and supraspinatus muscles.
      When the articular nerves were transected between their emergence from the main
      nerve trunk and the stimulation electrodes, the electromyographic discharge was
      abolished confirming the afferent nature of the nerves. The mean time delay ( +/-
      SD) from application of the stimulus to the peak of the recorded
      electromyographic activity was 3.2 +/- 0.27 msec. Anatomic dissection and
      staining of the capsule segments where the articular nerves terminated revealed
      mechanoreceptors consisting primarily of free nerve endings and Golgi tendon
      organs, Ruffini's endings, and pacinian corpuscles. The existence of a ligamento
      muscular reflex arc in the glenohumeral joint extends the concept of passive and
      active restraints of a joint by virtue of the synergy between ligaments and
      muscles. That such a reflex exists may advocate modification of surgical repairs
      of the capsule, leading to preservation of as many neurologic structures as
      possible; it may also form the foundation for new postsurgical therapeutic
      modalities.

PMID- 8742879
TI  - Spinoglenoid bone cyst causing suprascapular nerve compression.

PMID- 8742880
TI  - Suprascapular nerve entrapment at the spinoglenoid notch caused by a ganglion
      cyst.
AB  - A 34-year-old man had right infraspinatus muscle palsy and posterior aching of
      the shoulder caused by electromyographically confirmed suprascapular nerve
      entrapment. Sonography and magnetic resonance imaging revealed a cystic lesion at
      the spinoglenoid notch; this lesion was diagnosed as a ganglion. Operative
      removal led to immediate pain relief and incomplete recovery of the compressed
      branches of the suprascapular nerve.

PMID- 8742881
TI  - Apophysitis of the acromion.
AB  - We treated three patients with apophysitis of the acromion. These patients were
      two male athletes 12 and 14 years of age, respectively, and one female athlete 13
      years of age. They reported pain at the top of the shoulder during and after
      shoulder movement while playing sports but had no rest pain or disturbance of
      daily activities. Physical examination demonstrated marked local tenderness at
      the acromion and slight warmth. X-ray films showed sclerosis and irregularity of
      the secondary ossification center of the acromion. Bone scintigraphy carried out
      on one patient demonstrated increased uptake in that region. Conservative
      treatment was used for these patients. Recovery was gradual but satisfactory.

PMID- 8742882
TI  - American Shoulder and Elbow Surgeons closed meeting.

PMID- 8742883
TI  - 3-D radiation treatment planning: a new era.

PMID- 8742884
TI  - Assessment of the impact of local control on clinical outcome.

PMID- 8742885
TI  - Defining our goals: volume and dose specification for 3-D conformal radiation
      therapy.

PMID- 8742886
TI  - Imaging: the basis for effective therapy.

PMID- 8742887
TI  - The CT-simulation 3-D treatment planning process.

PMID- 8742888
TI  - Clinical interpretation of dose-volume histograms: the basis for normal tissue
      preservation and tumor dose escalation.

PMID- 8742889
TI  - Quantitative plan evaluation: TCP/NTCP models.

PMID- 8742890
TI  - Objective plan evaluation using a score function tool.

PMID- 8742891
TI  - Optimization of 3-D conformal radiation treatment plans.

PMID- 8742892
TI  - Quality assurance in 3-D treatment planning.

PMID- 8742893
TI  - Patient positioning devices: innovations for set-up precision, speed, and patient
      comfort.

PMID- 8742894
TI  - Computer-controlled radiation therapy and multileaf collimation.

PMID- 8742895
TI  - 3-D conformal therapy using beam intensity modulation.

PMID- 8742896
TI  - On-line portal imaging: contributions and limitations in clinical practice.

PMID- 8742897
TI  - Radiation Oncology Picture Archiving and Communications System: the electronic
      viewbox.

PMID- 8742898
TI  - Tissue inhomogeneity in the thorax: implications for 3-D treatment planning.

PMID- 8742899
TI  - 3-D conformal radiotherapy for lung cancer. The Washington University experience.

PMID- 8742900
TI  - 3-D conformal radiation therapy for non-small cell lung carcinoma. Clinical
      experience at the Memorial Sloan-Kettering Cancer Center.

PMID- 8742901
TI  - 3-D conformal radiotherapy in head and neck cancer. The Washington University
      experience.

PMID- 8742902
TI  - 3-D conformal radiation therapy in upper gastrointestinal cancer. The University
      of Michigan experience.

PMID- 8742903
TI  - 3-D conformal radiotherapy for carcinoma of the prostate. Clinical experience at
      the Memorial Sloan-Kettering Cancer Center.

PMID- 8742904
TI  - 3-D conformal radiotherapy for prostate cancer. The University of Michigan
      experience.

PMID- 8742905
TI  - 3-D treatment planning for brain tumors.

PMID- 8742906
TI  - 3-D conformal radiotherapy for brain tumors. The University of Michigan
      experience.

PMID- 8742907
TI  - Multi-institutional clinical trials: 3-D conformal radiotherapy quality
      assurance. Guidelines in an NCI/RTOG study evaluating dose escalation in prostate
      cancer radiotherapy.

PMID- 8742908
TI  - Where will 3-D conformal radiation therapy be at the end of the decade?

PMID- 8742909
TI  - Cardiovascular risk factors distribution in Hungarian adults.
AB  - Between 1992-1994 nutrition and nutritional status of 2259 persons (1173 men,
      1386 women) were examined in Hungary. The average of dietary fat intake was 38.0
      (5.7) in %, the median of P/S ratio 0.26-0.27, showing the dominance of saturated
      fatty acids. According to TC, 34.4% of the examined persons could be ranked to
      moderate and 27.4% to high risk groups. Regarding LDL-C levels, 27.2-27.2%
      belonged to both groups. TG indicated risk in 19.5% and 2.4%, respectively and
      HDL-C values were under the lower limit of normal range in 7.6% Sodium intake is
      three- to fourfold of the desirable quantity, that of potassium just reaches or
      remains under the recommended level. As a result, the value of Na/K ratio
      (mmol/mmol) is over 4. Borderline and/or define hypertension was found according
      to systolic pressure in 27.4 and 7.9% of men and in 18.1 and 5.2% in women.
      Diastolic pressure was in this domain in the case of men in 16.9 and 21.9%, in
      women in 12.7 and 16.1%. Hypertension is frequent both in middle-aged and old men
      and women. The high CVD mortality in Hungary may be in considerable part
      explained by the outlined risk factors.

PMID- 8742910
TI  - Prevention of thromboembolic events in valvular heart disease.
AB  - Thromboembolic events are major causes of morbidity and mortality in patients
      with native heart valve disease and artificial heart valves. Oral anticoagulation
      can reduce these complications. The indication for and intensity of oral
      anticoagulation depends on both, the risk for thromboembolic events and the risk
      of hemorrhage. The indications for oral anticoagulation in the various
      pathological conditions are defined. Risk factor adjusted intensity of oral
      anticoagulation and risk factor modification are new and very important aspects
      in the management of these patients which may lead to a reduction in
      anticoagulation associated complications and an improvement in antithrombotic
      effectivity. Further studies to identify the optimal therapeutic ranges of
      anticoagulation for the individual patient are needed. Multi-centre prospective
      randomized studies in this field should help us to answer the still open
      questions including new hemostatic molecular markers to further identify patients
      with different risk profiles.

PMID- 8742911
TI  - Hypertension and left ventricular hypertrophy.
AB  - In response to high blood pressure, left ventricular hypertrophy develops. But in
      hypertension, the myocardial hypertrophied structure is abnormal. The prevalence
      of this hypertrophy is influenced by age, gender, weight, race, genetics and the
      severity of high blood pressure. By echocardiography, it has been possible to
      detect non invasively and more precisely this hypertrophy and its anatomical
      pattern which is not uniform. This cardiac response is influenced by hemodynamic
      but also by non hemodynamic factors, but the exact mechanisms are not yet well
      understood. The humoral and tropic factors particularly affect the cardiac
      remodeling. Left ventricular hypertrophy has been noted by itself to be an
      independent risk factor for sudden death, ventricular arrhythmias, myocardial
      ischemia, and heart failure. Very early hypertension, diastolic dysfunction is
      noted. The progression to systolic failure in moderate hypertension usually
      occurs over several decades. According to the worse prognosis of left ventricular
      hypertrophy, it has been suggested that the reversibility of this anatomical
      modification by antihypertensive treatment is beneficial. Preliminary data
      support this idea.

PMID- 8742912
TI  - Cardiac function improvement 24 hours after isradipine SRO in patients with
      chronic stable angina: a double-blind randomized study.
AB  - We recently showed that Isradipine, a calcium antagonist from the dihydropyridine
      group, reduces ischemia and improves ventricular function at rest and during
      exercise, 2 hours after a single oral dose, in patients with chronic stable
      angina. In the present study, we evaluated the effects of long acting slow
      release oral (SRO) Isradipine (5 mg) compared to a placebo in 30 coronary
      patients with stable chronic angina, randomized in a double blind-fashion. The
      following parameters were obtained at rest and during submaximal exercise: left
      and right ventricular (LV, RV) ejection fractions (EF; %) and peak filling rate
      (PFR; EDV/s), assessed by gated radionuclide angiography, clinical symptoms,
      electrocardiograms (ECG, ST segment depression; mm), systolic and diastolic blood
      pressure (SBP and DBP; mm Hg). Patients were then given two oral doses of either
      Isradipine or placebo (one a day). The same parameters were reassessed, at rest
      and during n equivalent exercise, 48 hours later (24 hours after the last
      administration of the drug). The results after Isradipine (n = 14) showed, at
      rest, a significant increase in LVEF and Pfr (51 +/- 9 to 54 +/- 8 and 1.97 +/-
      0.44 to 2.36 +/- 0.71, respectively) and a decrease in DBP (93 +/- 11 to 87 +/-
      13); and during exercise, a significant increase in LVEF (51 +/- 11 tot 55 +/-
      13) and a decrease in ST segment depression (2.3 +/- 1.9 tot 1.9 +/- 1.6). No
      significant change was observed after placebo in the other 16 patients. We
      conclude that even 24 hours after an oral administration, Isradipine SRO
      maintains its beneficial effects both, at rest on LV systolic and diastolic
      function and pressure, and during exercise on ECG signs of ischemia with
      improvement in LV ejection fraction.

PMID- 8742913
TI  - Plasma endothelin-1 concentrations in patients with coronary artery disease
      during stress test before and after nisoldipine administration.
AB  - The purpose of this study was to determine the response of plasma levels of
      endothelin-1 (ET-1) to dynamic exercise in patients with coronary artery disease
      and chronic stable angina pectoris and positive exercise tolerance test, before
      and after treatment with the calcium antagonist nisoldipine (20 mg/day buccally
      for 7 days). Plasma ET-1 levels and hemodynamic parameters (blood pressure and
      heart rate) were determined at rest, at peak exercise and recovery. All patients
      had a positive electrically and clinically stress test and all of the eight
      patients did not developed ECG signs of myocardial ischemia after nisoldipine
      administration. Before nisoldipine treatment the plasma ET-1 levels did not
      increase significantly during exercise. After nisoldipine treatment the plasma ET
      1 levels were significantly lower at rest and during exercise compared with those
      revealed before calcium antagonist treatment. In conclusion our results suggest
      that in patients with chronic stable angina pectoris the treatment with calcium
      antagonist nisoldipine reduced ischemia and plasma ET-1 levels.

PMID- 8742914
TI  - Distribution of the different subtypes of hepatitis C virus in Japan and the
      effects of interferon: a nationwide survey.
AB  - Interferon (IFN) is now commonly used for the treatment of type C hepatitis;
      however, its effects differ depending upon the subtype of hepatitis C virus (HCV)
      being treated. It has been recently confirmed in many studies in Japan that the
      effectiveness of IFN treatment is poor in patients having type 1b and better in
      patients having type 2a HCV. However, the effects of IFN treatment on other
      subtypes of HCV were not clear because of the small number of patients in each
      hospital. In the present study, the effects of IFN treatment in patients with
      other HCV subtypes were analysed from nationwide data collected in Japan using a
      standard questionnaire. From this questionnaire, local differences in the
      distribution of HCV subtypes in Japan were also analysed. A standard
      questionnaire, consisting of questions about the number of patients with chronic
      type C hepatitis with different HCV subtypes and the number of patients showing
      different responses to IFN treatment, was sent to over 40 study groups in Japan.
      Answers to the questionnaire concerning HCV subtypes and the effects of IFN
      treatment were obtained from 26 and 22 hospitals, respectively, throughout Japan.
      The incidence of HCV type 1b was highest in the Kinki area (south-central Japan).
      The incidence of type 1b HCV decreased in parallel with distance from this area.
      The mortality rates of hepatic cancer in different areas were significantly
      correlated with the incidence of HCV type 1b. The efficacy of IFN treatment was
      significantly better for both types 2a and 2b HCV than for type 1b HCV; the
      efficacy of IFN treatment was poor in the mixed type of 1b and 2a and tended to
      be better in type 1a. The efficacy of IFN treatment for other types of HCV was
      also better. These results indicate that there are local differences in the
      distribution of HCV subtypes in Japan and that these differences may be closely
      associated with the clinical features of HCV-related liver disease. The efficacy
      of IFN treatment was significantly poorer in patients with the 1b-related type
      HCV than in patients with other types of HCV.

PMID- 8742915
TI  - Sequential changes in serum levels of individual bile acids in patients with
      chronic cholestatic liver disease.
AB  - In order to determine the value of serum bile acids in predicting the course of
      chronic cholestatic liver diseases, we measured individual serum bile acids
      serially, using high-performance liquid chromatography, over a 4 year observation
      period in 12 patients with primary biliary cirrhosis and six patients with
      primary sclerosing cholangitis. The changes in individual serum bile acids and
      the ratios thereof, conventional liver tests and Child-Turcotte and Mayo scores
      were compared between survivors (n = 10) and patients who underwent liver
      transplantation for (n = 3) or died of the liver disease (n = 5). Patients with a
      serum total chenodeoxycholic acid concentration at study entry that exceded 15
      mumol/L were 10 times more likely to die or need a liver transplant in the
      following 4 years than those with chenodeoxycholic acid levels < 15 mumol/L (P <
      0.05). None of the other biochemical parameters or clinicopathological scores
      could similarly discriminate between the two groups at entry. Time-dependent
      analyses for the cholic acid/chenodeoxycholic acid ratio, serum total bilirubin
      and albumin concentrations and Child-Turcotte and Mayo scores were able to
      differentiate between primary sclerosing cholangitis patients who died or were
      transplanted and those who were not, whereas age of the patients and other
      parameters did not. The taurocholic acid/taurochenodeoxycholic acid ratio fell
      during progression of primary biliary cirrhosis but rose in temporal relationship
      with primary sclerosing cholangitis. This differential pattern of change was
      unique compared with other clinical and laboratory indices. In conclusion, serum
      chenodeoxycholic acid levels and the cholic acid/chenodeoxycholic acid ratio in
      both diseases were independent indices that allowed for the prediction of
      survival or the need for liver transplantation. These indices are worthy of
      further examination in a larger group of patients as prognostic criteria for
      chronic cholestatic liver disease and in the assessment of the efficacy of
      therapeutic interventions, including liver transplantations.

PMID- 8742916
TI  - Vasopressin plus oxygen vs vasopressin alone in cirrhotic patients with portal
      hypertensive gastropathy: effects on gastric mucosal haemodynamics and
      oxygenation.
AB  - The effects of vasopressin plus oxygen and vasopressin alone on gastric mucosal
      perfusion and oxygenation were studied using reflectance spectrophotometry and
      laser Doppler velocimetry in 23 cirrhotic patients with portal-hypertensive
      gastropathy. The measurements were performed under basal conditions and after
      double-blinded administration of placebo (n = 7), vasopressin (0.3 U/min; n = 8)
      or vasopressin (0.3 U/min) plus nasal oxygen (4 L/min; n = 8). No significant
      effects on gastric mucosal haemodynamics and oxygenation were observed after
      placebo. In contrast, vasopressin and vasopressin plus oxygen induced a similar
      reduction in haemoglobin content (-26 +/- 2 and -21 +/- 4%, respectively P <
      0.01), and laser Doppler signal (-23 +/- 2 and -22 +/- 2%, respectively, P <
      0.01). Although each treatment induced a significant reduction in oxygen
      saturation (-21 +/- 2 and -7 +/- 1%, respectively P < 0.01), the effect was less
      pronounced in patients receiving the combination than in those receiving
      vasopressin alone (P < 0.01). These data suggest that vasopressin and vasopressin
      plus oxygen reduce gastric mucosal hyperaemia and that the oxygen supplement
      partially protects against gastric mucosal hypoxia during vasopressin infusion in
      cirrhotic patients with portal-hypertensive gastropathy.

PMID- 8742917
TI  - Monoclonal antibodies to rabbit hepatocyte myosin that cross-react with human
      liver myosin.
AB  - We prepared polyclonal and monoclonal antibodies against myosin purified from
      rabbit hepatocytes. Immunoblotting analyses revealed that the polyclonal antibody
      and four (HM1, HM2, HM3 and HM4) of five monoclonal antibodies reacted with
      myosin heavy chain. Chymotryptic cleavage of myosin yielded a 130 kDa fragment
      comprising the tail portion of the myosin heavy chain and a 67 kDa fragment
      comprising the ATP-binding active site of the myosin head. All active antibodies
      reacted with epitopes localized in the 130 kDa fragment. Monoclonal antibodies
      HM3 and HM4 and the polyclonal antibody reacted strongly with myosin heavy chains
      from a human liver homogenate prepared from a surgically resected liver specimen.
      Immunocytochemical analyses showed that myosin is localized along the plasma
      membrane as well as around the bile canaliculi in both rabbit and human
      hepatocytes. Immunocytochemical analyses on liver blocks obtained from those
      patients who suffered various types of diseases accompanying cholestasis clearly
      indicated a marked increase in pericanalicular myosin. This altered myosin
      localization is analogous to that observed in phalloidin-treated liver. Thus,
      myosin localization, determined using these antibodies, can provide a valid
      morphological basis for diagnosing the pathological state of the patient liver.

PMID- 8742918
TI  - Role of pentobarbitone anaesthesia and sympathetic tone in the haemodynamic
      effects of isosorbide dinitrate in rats with cirrhosis.
AB  - The haemodynamic effects of nitrovasodilators and their mechanisms of action on
      portal hypertension remain unclear. The splanchnic and systemic haemodynamic
      response to the infusion of isosorbide dinitrate (100 micrograms/kg per min), a
      nitrovasodilator, was investigated in cirrhotic rats. The role of the conscious
      state in the haemodynamic response to isosorbide dinitrate was examined using
      rats that were anaesthetized with pentobarbitone. The role of sympathetic tone in
      the haemodynamic response to isosorbide dinitrate was examined using rats
      pretreated with the ganglion blocker hexamethonium. Isosorbide dinitrate had no
      haemodynamic effects in conscious, unblocked normal and cirrhotic rats.
      Isosorbide dinitrate had no haemodynamic effects in normal and cirrhotic rats
      treated with hexamethonium. In normal anaesthetized rats, isosorbide dinitrate
      significantly decreased systemic vascular resistance (414 +/- 25 vs 290 +/- 26
      dyn.s/cm-5 per 100 g). In cirrhotic anaesthetized rats, isosorbide dinitrate
      significantly decreased mean arterial pressure (98 +/- 6 vs 79 +/- 7 mmHg),
      systemic vascular resistance (318 +/- 30 vs 207 +/- 10 dyn.s/cm-5 per 100 g),
      portal pressure (14.0 +/- 1.0 vs 11.3 +/- 0.9 mmHg) and portal territory vascular
      resistance (1362 +/- 163 vs 1031 +/- 182 dyn.s/cm5 per 100 g). In conclusion,
      this study shows that the portal hypotensive effects of isosorbide dinitrate
      depend upon the alterations of vascular tone by pentobarbitone.

PMID- 8742919
TI  - Hepatic HCV-RNA as a predictor of outcome after interferon therapy in patients
      with chronic hepatitis C.
AB  - Measurement of serum HCV-RNA is a useful index for evaluating the antiviral
      effect of interferon therapy in chronic hepatitis C. In the present study, we
      investigated whether the detection of hepatic HCV-RNA after interferon treatment,
      using a polymerase chain reaction assay, predicted long-term response to therapy
      in patients with chronic hepatitis C. Thirty-three patients underwent liver
      biopsies before and after interferon therapy. Histology and clinical courses were
      compared after treatment. Before therapy, serum and hepatic HCV-RNA was detected
      in specimens from 32 (97%) and 33 (100%) patients, respectively. Serum HCV-RNA
      became undetectable in samples from 22 (67%) patients; however, in 10 of these
      patients (45%), serum HCV-RNA levels relapsed after therapy. Hepatic HCV-RNA
      became undetectable in 14 patients after therapy and the serum aminotransferase
      concentration remained within normal limits during and following (24-92 weeks)
      therapy in 12 of these patients (86%). All 11 patients with detectable hepatic
      HCV-RNA also had serum HCV-RNA and elevated aminotransferase concentrations
      refractory to therapy. The absence of hepatic HCV-RNA at the end of interferon
      treatment thus predicted a long-term complete response to therapy with a
      sensitivity of 100%, a specificity of 90% and an accuracy of 94%. We conclude
      that hepatic rather than serum HCV-RNA is a more useful index for the prediction
      of the long-term efficacy of interferon therapy.

PMID- 8742920
TI  - Analysis of HLA alleles in Japanese patients with cirrhosis due to chronic
      hepatitis C.
AB  - Hepatitis C virus (HCV) leads to chronic liver disease in at least 50-60% of
      infected people and approximately 40-50% of these patients will go on to develop
      cirrhosis due to chronic hepatitis C (HCV-C). The pathogenic mechanisms that
      result in HCV-C are unknown. Sixty Japanese patients with HCV-C were examined for
      HLA-A, B, C and DR alleles by serologic typing and for HLA-DQB1 alleles by DNA
      typing using the polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) method. As the control population, 293 healthy un-related
      Japanese were used. The frequencies of HLA-B61, C(omega)3, DR4, DQB1*0401 and
      DQB1*0402 were increased, while those of HLA-DR9, DQB1*0301 and DQB1*0303 were
      decreased in the patients. The co-ordinate increase in the frequency of HLA-DR4,
      DQB1*0401 or 0402 and decrease in the frequency of DR9 or DQB1*0303 were
      suggestive of a strong linkage disequilibrium between HLA-DR4 and DQB1*0401 or
      0402 and between HLA-DR9 and DQB1*0303, respectively. From the odds ratio (OR)
      analysis, the combinations of HLA-C(omega)3+ DR4-DQB1*0401 or 0402, or HLA-B61 +
      DR4 - DQB1*0401 or 0402 increased the risk for developing HCV-C when compared to
      each HLA allele alone. This suggested an additive effect for these classes I and
      II HLA allele combinations in HCV-C. In contrast, HLA-DR9-DQB1*0303 and DQB1*0301
      may confer resistance to this disease. These results suggest the existence of HLA
      linked susceptibility genes to HCV-C.

PMID- 8742921
TI  - Sonographically-guided extracorporeal shockwave lithotripsy for pancreatic stones
      in patients with chronic pancreatitis.
AB  - Over a 2 year period, 10 patients with pancreatic stones due to alcohol induced
      chronic pancreatitis (proven by endoscopic retrograde pancreatography) underwent
      extracorporeal shockwave lithotripsy. Prior to shockwave therapy, all patients
      underwent endoscopic sphincterotomy. Targeting of shockwave lithotripsy was
      exclusively performed under sonographic control. All patients were treated with a
      second generation electrohydraulic spark gap lithotriptor and fragmentation of
      concrements could be achieved in all cases. Complete duct clearance was confirmed
      in seven patients by endoscopic retrograde pancreatography in one session, with
      endoscopic fragment extraction by basket and/or balloon catheter. In three
      patients, balloon dilation of concomitant strictures located in the head of the
      pancreas was performed prior to fragment extraction. All stone-free patients
      showed no further symptoms over the follow-up period of 12 months. Three patients
      in whom complete extraction of fragments was not successful experienced minor
      symptoms over the 12 month follow-up period.

PMID- 8742922
TI  - Estimation of usefulness of N-butyl-2-cyanoacrylate-lipiodol mixture in
      transcatheter arterial embolization for urgent control of life-threatening
      massive bleeding from gastric or duodenal ulcer.
AB  - We estimated the usefulness of a mixture of N-butyl-2-cyanoacrylate (NBCA) with
      lipiodol for transcatheter arterial embolization (TAE) used to control massive
      bleeding from gastric or duodenal ulcer. Thirty patients who had gastric or
      duodenal ulcers and massive bleeding that was uncontrollable by endoscopic
      procedures were included in this study. All patients were subjected to TAE
      (without NBCA in 23 and with NBCA in seven patients). Coils and/or gelfoam were
      also used. The achievement of haemostasis, occurrence of rebleeding and the time
      taken for TAE were compared between patients who received TAE without and with
      NBCA. Eighteen of 23 patients (78.3%) who received TAE without NBCA and six of
      seven patients (85.7%) who underwent TAE with NBCA achieved complete haemostasis
      without rebleeding. The time for TAE was significantly shorter in patients who
      received NBCA compared with those who did not (P = 0.0095). TAE using NBCA or a
      combination of NBCA and coils achieved a rapid, complete embolization regardless
      of vascular distribution or arterial diameter. Thus NBCA is considered to be
      useful as a secondary embolization material in TAE that is urgently conducted to
      control massive bleeding from gastric or duodenal ulcers.

PMID- 8742923
TI  - Adaptation of the gastric epithelium to injury is maintained in vitro and is
      associated with increased TGF-alpha expression.
AB  - Adaptation is the name given to the progressive decrease in gastric mucosal
      damage following repeated dosing with damaging agents. This study aimed to
      determine whether adaptation is an intrinsic property of the gastric epithelium
      and the role in the development of this process of TGF alpha. Rats were given
      either one or six daily doses of 10 mg/kg diclofenac or six daily doses of
      vehicle only (1% methylcellulose). On the 7th day, antral mucosa was taken for
      organ culture and loaded with [51Cr]. Explants were challenged with ethanol and
      damage quantified by [51Cr] release. In a separate experiment, rats were dosed as
      above and the gastric mucosa was extracted and TGF alpha quantified by RIA. The
      rate of [51Cr] release was significantly lower after ethanol injury in explants
      from rats previously adapted to diclofenac (9.2 +/- 2.5%) compared with those
      exposed to a single damaging dose of diclofenac (25.9 +/- 3.5%) or vehicle only
      (26.4 +/- 3.3%; P < 0.01; ANOVA). The concentration of TGF alpha was
      significantly higher in the gastric epithelium of rats adapted to diclofenac than
      other groups (P < 0.05; t-test). Cross adaptation of the gastric mucosa to injury
      has therefore been demonstrated in antral mucosal explants in organ culture while
      TGF alpha peptide expression is elevated in the adapted gastric mucosa. These
      findings suggest that adaptation is an inherent property of the gastric
      epithelium and it is likely that TGF alpha may play a role in its maintenance.

PMID- 8742924
TI  - Correlation between transmucosal potential difference and morphological damage
      during aspirin injury of gastric mucosa in rats.
AB  - The potential difference (PD) that is maintained across healthy gastric mucosa is
      thought to be due to asymmetric ion pumping combined with resistance to back
      diffusion of the separated charge. However, the structures that are responsible
      for this have not been clearly defined. This study examined the temporal changes
      in PD in rat stomach after injury by a single dose of aspirin. Multiple linear
      regression was used to compare this with the time course of several parameters of
      histological damage: (i) the per cent mucosal length showing superficial
      (confined to surface and gastric pits), deep (involving the isthmus or deeper in
      oxyntic glands) and total damage; (ii) the number of discrete erosions; and (ii)
      the total area of erosions per cm sectioned. Mucosal PD fell during the first 30
      60 min after aspirin. Superficial damage appeared early and was already
      recovering by this time. The time course of deep damage more closely matched the
      alterations in PD and stepwise regression analysis showed that this could be
      predicted by the amount of deep damage alone (P < 0.001). Changes in transmucosal
      PD after acute aspirin injury probably reflect damage to structures in the
      oxyntic glands and not just the breaking of the surface and pit cell 'barrier'.

PMID- 8742925
TI  - Clinical and histological features of gastric antral vascular ectasia: successful
      treatment with endoscopic laser therapy.
AB  - Gastric antral vascular ectasia is a rare but important cause of chronic
      gastrointestinal bleeding. We report five patients in whom endoscopic laser
      therapy successfully controlled repeated blood loss. The patients were elderly
      (age range: 61-84 years; mean age: 75 years) and three of them were female.
      Endoscopically, all patients presented with a characteristic antral appearance of
      either ecstatic vascular 'stripes' radiating out from the pylorus, or multiple
      cherry-red spots. In all patients, the gastric mucosal biopsy specimens showed
      dilatation of the capillaries with focal fibrin thrombi and fibromuscular
      hyperplasia. Marked improvement of both endoscopic and histological features was
      achieved with endoscopic laser treatment using Nd-YAG laser photocoagulation. Its
      importance lies in its recognition and successful treatment with endoscopic laser
      therapy, which offers an effective and relatively safe alternative to surgery,
      particularly in elderly patients.

PMID- 8742926
TI  - Mental retardation and colorectal disease: colonoscopic mass screening to
      determine whether the risk of adenomatous polyposis syndrome is increased in the
      mentally retarded.
AB  - Adenomatous polyposis syndrome (APS) is often associated with mental retardation,
      but whether there is a causal relationship between the two is unknown. This study
      was initiated to determine colorectal disease rates among mentally retarded
      subjects and whether they are at risk of developing colorectal cancer.
      Colonoscopic mass screenings were conducted to detect the presence of colonic
      neoplasms in 134 patients housed at an institution for the mentally retarded. The
      ages of these subjects ranged from 32 to 69 years (mean: 44 years) and their IQ
      scores ranged from 35 to 63. Screening presented no difficulties and the colonic
      regions up to the caecum were inspected in all patients. Polyps were found in 24
      patients (17.9%), an abnormal fixation in two (1.5%), melanosis coli in two
      (1.5%) and haemorrhoids in two (1.5%). Thirteen subjects had a single polyp
      (54%), five had two polyps (21%), three had three polyps (12.5%) and three had
      four polyps (12.5%). Twenty one polyps were less than 5 mm in diameter, 14 were 5
      9 mm and nine were 10 mm or larger. No cases of APS were detected during this
      mass screening programme. The mentally retarded patients in this study were not
      found to be at a high risk of developing either APS or colon cancer.

PMID- 8742927
TI  - Role of endothelin-1 in repeated electrical stimulation-induced microcirculatory
      disturbance and mucosal damage in rat stomach.
AB  - The aim of the present study was to clarify the involvement of endogenous
      endothelin in the pathogenesis of gastric mucosal damage. The rat stomach was
      exposed and repeated electrical stimulation (RES) was applied to the small
      arterial wall close to the lesser curvature. Significant mucosal haemorrhagic
      lesions (ulcer and erosion) were noted within 30 min after RES. Intravital
      microscopic observations revealed that an arteriolar constriction occurred in the
      submucosal layer of the rat stomach approximately 5 min after the completion of
      RES. Following the arteriolar constriction, the mucosal blood flow of the rat
      stomach, which was monitored by using a laser Doppler velocimeter, decreased to
      approximately 30% of the control value. The plasma immunoreactive endothelin-1
      level in the regional blood of the stomach was significantly increased
      immediately after RES preceding the decrease in mucosal blood flow.
      Immunohistochemical studies revealed that endothelin-1 and big-endothelin-1 were
      detectable in the arteriolar endothelium around the muscularis mucosa, supporting
      the involvement of endothelin-1 in RES-induced mucosal ischaemia. In addition, BQ
      123, a specific antagonist of the endothelin A (ETA) receptor, attenuated the
      reduction of blood flow and the development of haemorrhagic lesions observed in
      gastric mucosa subjected to RES. The results of the present study suggest that an
      excessive production of endothelin-1 in the arteriolar endothelium leads to
      microvascular derangements accompanied by haemorrhagic alterations of the gastric
      mucosa.

PMID- 8742929
TI  - Metronidazole resistance: a predictor of failure of Helicobacter pylori
      eradication by triple therapy.
AB  - Triple therapy (bismuth and two antibiotics) will eradicate Helicobacter pylori
      infection in 70-90% of subjects. Treatment failure has been attributed to patient
      compliance and antimicrobial drug resistance. The aim of this study was to
      examine factors influencing the eradication of H. pylori following triple
      therapy. Thirty seven subjects with H. pylori cultured from antral biopsies were
      treated with colloidal bismuth subcitrate (120 mg qid for 2 weeks), metronidazole
      (400 mg tid for 1 week) and amoxycillin (500 mg tid for 1 week). Pretreatment
      isolates of H. pylori were tested for metronidazole susceptibility by agar
      dilution according to the National Committee for Clinical Laboratory Standards
      guidelines. Factors including age, sex, clinical diagnosis and metronidazole
      resistance were evaluated in relation to H. pylori. The overall metronidazole
      resistance was 32%. Metronidazole resistant strains were more frequent in
      females, with a resistance rate of 54%. Helicobacter pylori eradication occurred
      in 68% of patients with a metronidazole susceptible stain and only 17% of
      patients with a metronidazole resistant strain (P < 0.03). Helicobacter pylori
      eradication is dependent upon susceptibility to metronidazole. This data would
      support the role for routine metronidazole susceptibility testing using
      appropriate standardized methods when triple therapy is to be considered.

PMID- 8742928
TI  - Polymerase chain reaction diagnosis of Helicobacter pylori in gastroduodenal
      diseases: comparison with culture and histopathological examinations.
AB  - Helicobacter pylori has been associated with a variety of upper gastrointestinal
      diseases. Histopathological examination and culture are considered to be the more
      specific tests in the diagnosis of H. pylori infection. In the present study, we
      evaluated the efficiency of a polymerase chain reaction (PCR) assay of the H.
      pylori urease A gene as a procedure in the diagnosis of gastric H. pylori
      infection in various gastroduodenal diseases. Biopsy specimens were obtained from
      the antral mucosa of 83 patients during endoscopic examination and were submitted
      to three tests for the detection of H. pylori infection. The detection rates of
      H. pylori using PCR, histopathological examination and culture were 84, 77 and
      63%, respectively. When the infection was defined, by the agreement of culture
      and histopathological examination or by positive culture, the PCR assay had a
      sensitivity of 98.1% and a specificity of 84.6%. When the infection was defined
      by a positive result of either two of the three tests or by positive culture, the
      PCR assay had a sensitivity of 98.6% and a specificity of 85.7%. We conclude that
      the PCR assay is a valuable test for the diagnosis of H. pylori infection in
      gastroduodenal diseases.

PMID- 8742930
TI  - The transjugular intrahepatic portosystemic stent-shunt: a review of the
      literature and own experiences.
AB  - The transjugular intrahepatic portosystemic stent-shunt (TIPS) technique consists
      of a transhepatic puncture of the portal vein and stenting of the parenchymal
      tract between the hepatic and portal veins. Complications of both puncture and
      stenting are observed in approximately 5% of procedures. Most of the
      complications are without clinical consequences and the procedural mortality is
      very low in experienced hands (1%). During a 1 year follow up, 35% of patients
      were seen to develop stenosis and 15% developed occlusion of the stent-shunt.
      However, in spite of the considerable incidence of stenosis/occlusion, the rate
      of variceal rebleeding is rare when patients are followed up carefully by duplex
      sonography, which allows accurate and early detection of shunt insufficiency. One
      of the major long-term clinical problems of TIPS is the induction or worsening of
      hepatic encephalopathy. Although most patients respond to medical treatment, some
      develop debilitating encephalopathy or progressive liver failure. In these
      patients, reduction of shunt flow by the implantation of a reducing stent, or its
      occlusion with a balloon catheter, may be indicated. In conclusion, in spite of
      many complications, TIPS is relatively safe and efficient and hepatic
      encephalopathy is manageable in most cases.

PMID- 8742931
TI  - Pedunculated extraluminal leiomyoma of the sigmoid colon.
AB  - Leiomyoma of the colon is an extremely rare entity. Reports are those of sessile
      intraluminal lesions that are accessible to colonoscopy. This is a case report of
      a pedunculated extraluminal leiomyoma of the sigmoid colon which has not been
      previously reported.

PMID- 8742932
TI  - Portal-systemic shunting in a patient with normal portal vain pressures and
      histological evidence of idiopathic portal hypertension.
AB  - Although idiopathic portal hypertension (IPH) is clinically characterized by
      portal hypertension and marked splenomegaly, we have experienced a case of
      spontaneous portal-systemic shunt without splenomegaly in whom the liver
      histology resembled IPH but with normal portal pressure. We admitted a 64 year
      old man who had suffered from hepatic encephalopathy for 2 years. Laparoscopy
      revealed a dark grey liver with a sharp edge and a concave surface. Examination
      of a liver biopsy specimen revealed peri-portal fibrosis consistent with IPH. A
      single, large, portal-systemic shunt was identified by percutaneous transhepatic
      portography. The shunt arose from the left gastric vein and flowed through the
      left renal vein into the inferior vena cava. No varices were identified. There
      were no morphological changes in the hepatic or portal veins. Portal vain
      pressure was normal. There was a slight difference between the portal pressure
      and the wedged hepatic vein pressure, suggesting a presinusoidal block. This case
      raises important questions concerning the aetiology of IPH and the relationship
      between portal hypertension and the development of collateral venous circulation.

PMID- 8742933
TI  - Control of colonic variceal haemorrhage with a somatostatin analogue.
AB  - A 64 year old caucasian male with known alcoholic liver disease presented with
      rectal bleeding. The patient bled repeatedly despite resuscitation. A sigmoid
      colectomy was performed following an angiogram. Large colonic, rectal and
      mesenteric variceal vessels were noted at surgery. Further bleeding
      postoperatively was rapidly controlled with octreotide infusion. Octreotide may
      be as useful in the control of colonic variceal bleeding as it is in the control
      of oesophageal variceal bleeding.

PMID- 8742934
TI  - In-vivo buccal delivery of fluorescein isothiocyanate-dextran 4400 with
      glycodeoxycholate as an absorption enhancer in pigs.
AB  - Buccal delivery of fluorescein isothiocyanate labeled dextran 4400 (FD4) was
      investigated in-vivo in pigs. The delivery device consisted of an application
      chamber with a solution of FD4 and was adhered to the buccal mucosa for 4 h using
      an adhesive patch. A randomized crossover study including intravenous
      administration and buccal delivery without and with 10 mM sodium
      glycodeoxycholate (GDC) as absorption enhancer was performed in five pigs. After
      buccal administration, steady state plasma levels were rapidly reached.
      Coadministration of 10 mM GDC increased the absolute bioavailability of FD4 from
      1.8 +/- 0.5% to 12.7 +/- 2.0%. Since FD4 is a macromolecular and hydrophilic
      compound such as peptide and protein drugs, buccal delivery would provide an
      adequate alternative to the parenteral administration of these drugs.

PMID- 8742935
TI  - Preparation and characterization of polymorphs for an LTD4 antagonist, RG 12525.
AB  - This report describes the preparation and characterization of two polymorphic
      forms of RG 12525, a leukotriene D4 (LTD4) antagonist. Polymorph I is prepared by
      recrystallization from methanol or titration of the sodium salt of RG 12525 with
      citric acid. Polymorph II is prepared by recrystallization from methanol or
      titration of the ammonium salt of RG 12525 with citric acid. The polymorphic
      system is enantiotropic, with pure form I melting at 154 degrees C, 3 deg less
      than the melting temperature of form II. Form I is thermodynamically more stable
      than form II at room temperature. These polymorphic forms are differentiated
      using microscopy, differential scanning calorimetry (DSC), infrared spectroscopy
      (IR), and powder X-ray diffraction (XRD) analysis. Solubility properties from 31
      to 72 degrees C were determined to be similar for both forms. The calculated
      solubilities at 25 degrees C are 7.6 and 9.8 microM for forms I and II,
      respectively. The free energy change from form II to form I at 25 degrees C is 
      0.15 kcal/mol. Thermodynamic properties of the system are summarized using a
      schematic free energy diagram.

PMID- 8742936
TI  - Adsorption of betamethasone disodium phosphate on ethylcellulose latex: an
      electrokinetic study.
AB  - The use of polymer latexes as vehicles for drug transport and controlled delivery
      in the body is a very active research field in applied colloid science. In this
      work, the polymer chosen is a commercially available ethylcellulose-based
      material, Aquacoat. We report electrokinetic (electrophoresis) data on this
      polymer in the presence of the soluble glucocorticoid betamethasone disodium
      phosphate (BMP). The electrophoretic mobility of the particles becomes more
      negative as the concentration of BMP in the medium is increased between 10(-5)
      and 10(-3) M, this demonstrating that the negative species produced upon
      dissolution of BMP adsorb on the particles; this trend is reversed for higher
      concentrations due to the phenomenon of double layer thickness. When pH is
      increased at constant BMP concentration, the negative mobility increases in
      absolute value, but it reaches lower values than attained in the absence of BMP.
      This is interpreted as another consequence of adsorption, since the ionization
      constants of the phosphate and sulfate groups are different. Such adsorption is
      confirmed and measured by spectrophotometric analysis of the supernatants after
      centrifugation of the suspensions; it is found that the adsorption density
      increases with the initial concentration of BMP in the medium, an almost vertical
      isotherm being obtained for concentrations above 5 x 10(-3) M, possibly due to
      bidimensional aggregation of the adsorbed molecules and multilayer adsorption at
      higher concentrations. It is found that the adsorbed amount increases with the
      ionic strength of the medium as a consequence of screening of the particle and
      BMP charges, whereas these electrostatic contributions to adsorption manifest
      also in the pH dependence of adsorption. IR analysis of the particles after
      equilibration with BMP solutions of increasing concentration agrees well with
      adsorption data.

PMID- 8742937
TI  - Physiologic pharmacokinetic modeling of gastrointestinal blood flow as a rate
      limiting step in the oral absorption of digoxin: implications for patients with
      congestive heart failure receiving epoprostenol.
AB  - A previously validated physiologically based pharmacokinetic model was used to
      examine whether epoprostenol-induced increases in gastrointestinal blood flow
      (Qg) could alter digoxin systemic bioavailability to a clinically significant
      extent in severe congestive heart failure (CHF) patients. A series of simulations
      was conducted in which the influences of apparent gut tissue-to-plasma partition
      coefficient (Kg) and Qg on digoxin bioavailability were evaluated. Since
      epoprostenol also increases blood flow to the liver and kidneys, the effect of
      concurrent increases in regional blood flow to these organs on digoxin
      bioavailability also was evaluated. A range of Qg was studied from 25 L/h
      (assumed mesenteric arterial flow in CHF) to 65 L/h (portal venous flow in normal
      adults), and the area under the simulated digoxin concentration-time curve was
      used to calculate absolute digoxin bioavailability in each case. Simulations were
      conducted at a range of Kg from 1 to 50 (physiologically relevant range 5-25). At
      low values of Kg, the influence of changes in Qg on digoxin bioavailability was
      minimal. However, as apparent distribution into gut tissue increased (consistent
      with visceral congestion), the effect of changes in Qg was more substantial. In
      the physiologically relevant range of Kg, 40-160% increases in Qg were associated
      with approximately 6-40% increases in digoxin bioavailability. Therefore, the
      decrease in digoxin oral clearance previously observed in CHF patients receiving
      epoprostenol may be ascribed to increases in digoxin bioavailability, secondary
      to epoprostenol-induced increases in Qg.

PMID- 8742938
TI  - Oral absorption of anti-acquired immune deficiency syndrome nucleoside analogues.
      2. Carrier-mediated intestinal transport of stavudine in rat and rabbit
      preparations.
AB  - The intestinal transport and metabolism of stavudine (d4T), a nucleoside analogue
      of thymidine used in the treatment of AIDS, was studied using single-pass
      intestinal perfusion (SPIP), intestinal brush-border membrane vesicles (BBMV),
      and mucosal homogenates in rats and rabbits. In the SPIP, d4T demonstrated
      concentration-dependent mean wall permeability (P+/-w) at perfusate
      concentrations ranging from 0.001 to 25 mM. In coperfusion studies using 0.1 mM
      thymidine, 1 mM formycin B, or 5 microM NBTI as putative inhibitors of d4T
      transport, the P+/-w of 5 microM d4T was reduced to 48%, 62%, and 70% of the
      control value, respectively, suggesting the involvement of multiple nucleoside
      carriers in the intestinal uptake of d4T. d4T uptake in rat BBMV was
      significantly greater in the presence of a sodium ion gradient compared with a
      sodium-free (choline) gradient. The permeability of d4T, in the presence of a
      sodium gradient, was concentration-dependent and inhibited by 10 mM thymidine but
      not significantly reduced by 10 mM formycin B. In the presence of 10 microM NBTI,
      the permeability of d4T was not inhibited; however; the binding of d4T to rat and
      rabbit BBMV was significantly reduced. Formycin B did not significantly reduce
      the d4T uptake in rat or rabbit BBMV suggesting that d4T does not interact with
      the purine-selective N1 nucleoside carrier. However, because formycin B inhibited
      d4T uptake in the SPIP and since d4T inhibited formycin B uptake in rat but not
      rabbit BBMV, it appears to interact with the N3 carrier which has been
      demonstrated in rat but not rabbit intestine. Also, an interaction with the
      sodium-independent facilitative transporter at the basolateral membrane cannot be
      ruled out. The low hybrid K(m) and high passive permeability of d4T likely
      account for the lack of saturable absorption behavior observed in humans, whereas
      the brush-border and intracellular stability of d4T preserve the high
      bioavailability observed after oral dosing.

PMID- 8742939
TI  - Development of inherently echogenic liposomes as an ultrasonic contrast agent.
AB  - Ultrasonic contrast agents have been developed for improved assessment of blood
      flow and tissue perfusion. Many of these agents are not inherently acoustically
      reflective (echogenic), and nearly all are not suitable for tissue specific
      targeting. The purpose of this study was to develop acoustically reflective
      liposomes, which are suitable for antibody conjugation, without using gas or any
      other agent entrapment. Echogenic liposomes were prepared from
      phosphatidylcholine (PC), phophatidylethanolamine (PE), phosphatidylglycerol
      (PG), and cholesterol (CH), using a dehydration/rehydration method. The
      formulation was optimized for higher acoustic reflectivity by varying the lipid
      composition. Liposomes were imaged with a 20 MHz intravascular ultrasonic imaging
      catheter. Echogenicity levels were expressed using pixel gray scale. The presence
      of PE and PG at specific concentrations improved echogenicity due to their
      effects on liposomal morphology as confirmed by freeze-etch electron microscopy.
      The acoustic reflectivity of liposomes was retained when liposomes were treated
      with blood at room temperature and 37 degrees C under in vitro conditions. It was
      demonstrated that the liposomes were also acoustically reflective in vivo after
      they were injected into a miniswine model. We have developed echogenic liposomes
      that are stable and suitable for tissue specific targeting as a novel contrast
      agent. This new contrast agent can be used for ultrasonic image enhancement
      and/or treatment of targeted pathologic sites.

PMID- 8742941
TI  - Design, synthesis, and pharmacokinetic evaluation of a chemical delivery system
      for drug targeting to lung tissue.
AB  - We espouse the application of a novel chemical delivery system (CDS) approach to
      a delivery mechanism for drug targeting to lung tissue using the 1,2-dithiolane-3
      pentyl moiety of lipoic acid as the "targetor moiety". The synthesis and the
      physicochemical and pharmacokinetic evaluation of a CDS modeling the lipoyl and
      other ester derivatives of chlorambucil (an antineoplastic agent) and cromolyn (a
      bischromone used in antiasthma prophylaxis) as compared with their respective
      parent drugs are described. The chlorambucil CDS was synthesized by esterifying
      the alcohol derivative of lipoic acid with chlorambucil using
      dicyclohexylcarbodiimide as the coupling agent. The cromolyn CDS was prepared by
      a multistep synthetic procedure culminating in the reaction of the alkyl bromide
      derivative of lipoic acid with the disodium salt of the bischromone compound. All
      the esters were highly lipophilic unlike the parent compounds. The in-vitro
      kinetic and in-vivo pharmacokinetic studies showed that the respective CDSs were
      sufficiently stable in buffer and biological media, hydrolyzed rapidly into the
      respective active parent drugs, and significantly enhanced delivery and retention
      of the active compound to lung tissue in comparison with the underivatized parent
      compounds used in conventional therapy.

PMID- 8742942
TI  - Artificial neural networks as a novel approach to integrated pharmacokinetic
      pharmacodynamic analysis.
AB  - A novel model-independent approach to analyze pharmacokinetic (PK)
      pharmacodynamic (PD) data using artificial neural networks (ANNs) is presented.
      ANNs are versatile computational tools that possess the attributes of adaptive
      learning and self-organization. The emulative ability of neural networks is
      evaluated with simulated PK-PD data, and the power of ANNs to extrapolate the
      acquired knowledge is investigated. ANNs of one architecture are shown to be
      flexible enough to accurately predict PD profiles for a wide variety of PK-PD
      relationships (e.g., effect compartment linked to the central or peripheral
      compartment and indirect response models). Also, an example is given of the
      ability of ANNs to accurately predict PD profiles without requiring any
      information regarding the active metabolite. Because structural details are not
      required, ANNs exhibit a clear advantage over conventional model-dependent
      methods. ANNs are proved to be robust toward error in the data and perturbations
      in the initial estimates. Moreover, ANNs were shown to handle sparse data well.
      Neural networks are emerging as promising tools in the field of drug discovery
      and development.

PMID- 8742940
TI  - Controlled transdermal delivery of fentanyl: characterizations of pressure
      sensitive adhesives for matrix patch design.
AB  - Transdermal delivery of fentanyl from various adhesive matrix formulations to
      achieve a steady-state skin flux was investigated. For this purpose, various
      pressure-sensitive adhesives selected from the three chemical classes of polymers
      (polyisobutylene (PIB), acrylate, and silicone adhesives) were characterized with
      respect to fentanyl's solubility, diffusion coefficient, and permeability
      coefficient. The solubility of fentanyl in various pressure-sensitive adhesives
      at 32 degrees C was determined by the drug absorption-desorption method. The
      solubilities of fentanyl in these adhesives were in the following order: acrylate
      > silicones > PIB. The permeability coefficient and diffusion coefficient of
      fentanyl in these adhesives were determined by the membrane diffusion method. The
      diffusion coefficient rank order was silicone-2920 > silicone-2675 > or =
      acrylate > PIB. The release profiles of fentanyl in the aqueous buffer from these
      adhesives with 2-4% drug loading was evaluated. The release rate of fentanyl from
      the acrylate polymer was significantly higher than those of silicone and PIB
      adhesives. The in vitro flux of fentanyl through cadaver skin from various
      adhesives with 2% drug loading was determined at 32 degrees C using modified
      Franz diffusion cells. The skin fluxes of fentanyl from silicone-2920 and PIB
      adhesives were 6.3 +/- 0.7 and 3.1 +/- 0.3 micrograms/cm2/h, respectively. On the
      other hand, the skin fluxes of fentanyl from acrylate and silicone-2675 adhesive
      matrices were about 1 microgram/cm2/h. The effect of drug loading on skin flux
      was investigated using PIB as a model adhesive. The drug released in the
      phosphate buffer (pH = 6.0) increased linearly as the drug loading in the PIB was
      increased from 1% to 4%; and as the drug loading exceeded 4%, an initial burst
      effect followed by a zero-order release was observed. The skin flux of fentanyl
      increased proportionally as the drug loading in the PIB adhesive was increased
      from 1 to 4%, and a plateau was reached beyond 4% drug loading. These results
      suggest that fentanyl concentration in the PIB adhesive might have reached
      saturation above 4% drug loading and that the optimum skin flux was accomplished
      from such a system because of attainment of maximum thermodynamic activity.

PMID- 8742943
TI  - Fluorescent probe studies of the interactions of 1-alkyl-2-pyrrolidones with
      stratum corneum lipid liposomes.
AB  - Previously, the effects of a series of 1-alkyl-2-pyrrolidones (APs; C2-C8) on the
      lipoidal pathway of hairless mouse skin (HMS) were studied with a parallel
      pathway skin model. At their isoenhancement concentrations, these 1-alkyl-2
      pyrrolidones induce the same transport enhancement (isoenhancement factor, EHMS)
      on the lipoidal pathway of the stratum comeum for the probe permeants studied. In
      the present study, the fluidizing effects of APs upon the stratum comeum lipid
      liposome (SCLL) bilayer were investigated under these isoenhancement conditions
      using steady state anisotropy and fluorescence lifetime studies with fluorescent
      probes 2-, 6-, and 9-(9-anthroyloxy)stearic acids, 16-(9-anthroyloxy)palmitic
      acid, and 1,6-diphenyl-1,3,5-hexatriene to examine a possible correlation between
      the fluidizing properties of APs and their enhancement effects on transdermal
      drug transport. Time-resolved fluorescence decay studies were also conducted to
      further investigate the fluidizing properties of APs and add support to the
      steady-state fluorescence results. Under an isoenhancement condition of EHMS =
      10, these APs fluidized the alkyl chains of the lipids at intermediate depths (C6
      C9) in the SCLL bilayer (a 40-50% decrease in the rotational correlation times)
      but did not significantly change the fluidity in the deep hydrophobic region of
      the bilayer. Three rotational correlation times were deduced from the global
      simultaneous analysis in time-resolved fluorescence decay measurements. The
      slowest of these (greater than 1000 ns) was attributed to the global motion of
      SCLLs and is probably related to the static component of steady-state anisotropy.
      The other two rotational correlation times (on the order of nanoseconds) were in
      the range expected for the local motion of the fluorophores and may correspond to
      their vibrational and rotational motions. When the concentrations of APs were
      increased (increasing the EHMS value), the static component (alpha) decreased.
      This suggests that APs might induce a general fluidizing effect upon the lipid
      bilayer (i.e., a decrease in the order of the lipid bilayer). The decrease in the
      longer rotational correlation time (on the order of nanoseconds) with increasing
      EHMS value, on the other hand, indicates a possible increase in the "cavity
      volume" for the hindered motions of the fluorophores (i.e., an increase in the
      free volume at intermediate depths in the bilayer).

PMID- 8742944
TI  - Structure-function relationship among Quillaja saponins serving as excipients for
      nasal and ocular delivery of insulin.
AB  - The purpose of this investigation was to explore the structure-function
      relationship among naturally occurring Quillaja saponins and derivatives for
      their ability to stimulate insulin delivery from nosedrops and eyedrops and to
      test the hypothesis that stimulation of peptide drug delivery was correlated with
      surfactant strength. Native saponins, including QS-21, were purified from an
      aqueous extract of Quillaja saponaria bark by adsorption chromatography and HPLC.
      Native saponins were then deacylated by mild alkaline hydrolysis to form DS-1 and
      DS-2, derivatives that are smaller and more hydrophilic than their parent
      compounds. DS-1 was further treated either to reduce an aldehyde residue to form
      DS-1(R) or to remove the fucose-containing oligosaccharide to form QH-957. Rats
      receiving eyedrops or nosedrops formulated with insulin, but without any Quillaja
      saponins, showed no hypoglycemic response. Rats receiving eyedrops or nosedrops
      formulated with insulin plus saponins showed a dose-dependent hypoglycemic
      response, with the following rank order: QS-21 > DS-1 > DS-1(R) > DS-2 > QH-957.
      Surfactant strength was determined by measurement of the critical micellar
      concentration (cmc) and hemolysis of sheep erythrocytes. The cmc was lowest for
      the parent saponins QS-21 and QS-18, and increased for the deacylated saponin
      derivatives DS-1, DS-2, and QH-957; hemolysis of sheep erythrocytes was observed
      at low concentrations (approximately 0.006 mM) of the parent saponins, QS-21 and
      QS-18, at intermediate concentrations (0.06-0.08 mM) of DS-1 and DS-2, and at
      higher concentrations of DS-1(R) (0.45 mM) and QH-957 (1.5 mM). Hence, efficacy
      as an absorption-enhancing agent was greatest in those saponins with the lowest
      hemolytic titers and cmc values. However, this relationship was not a strict one,
      because DS-1, which differs from DS-2 only in the absence of one glucose residue,
      was significantly more potent than DS-2 in stimulating the absorption of insulin.
      DS-1 and DS-2 share a similar cmc and hemolytic titer, so this difference in
      efficacy must be due to some specificity beyond simple surfactant strength.
      Furthermore, DS-1 does not trigger an immune response when administered to
      animals, whereas QS-21 is a strong immune system activator. Therefore, DS-1 has
      emerged as an interesting candidate for inclusion in an eyedrop or nosedrop
      formulation.

PMID- 8742945
TI  - A physicochemical basis for the effect of food on the absolute oral
      bioavailability of halofantrine.
AB  - Halofantrine hydrochloride (Hf.HCl) is a highly lipophilic phenanthrenemethanol
      antimalarial. The poor and erratic absorption of Hf after oral administration has
      been implicated in some treatment failures. Food increases the oral
      bioavailability of Hf in humans approximately 3-5-fold, although neither the
      absolute bioavailability nor the basis for the food effect has been fully
      defined. In this study, the mean (+/-SD, n = 3) absolute oral bioavailability of
      250 mg Hf.HCl tablets in beagles was 8.6 +/- 5.3% in the fasted state, which
      increased approximately 12-fold when administered postprandially. These data
      indicate that Hf.HCl is efficiently absorbed from the postprandial intestinal
      environment. The solubility and intrinsic dissolution rate of Hf.HCl were
      investigated as a function of bile salt concentration (sodium taurocholate, NaTC,
      0-30 mM) and micellar composition (4:1 NaTC:lecithin). At premicellar (fasted)
      concentrations of NaTC (< 5 mM), the solubility and intrinsic dissolution rate
      were very low (< 15 micrograms/mL; < 0.01 microgram s-1 cm-2). At NaTC
      concentrations typical of the postprandial state, the solubility and dissolution
      rate improved dramatically. For example, solubility in 30 mM NaTC increased
      approximately 1000-fold relative to buffer control, with even greater enhancement
      (3000-fold) associated with mixed micellar systems. These data suggest that the
      improved absorption of Hf.HCl in the fed state is most likely due to the
      increased solubilization and dissolution of the drug in the presence of bile salt
      mixed micelles.

PMID- 8742946
TI  - Comparative in vitro evaluation of several colloidal systems, nanoparticles,
      nanocapsules, and nanoemulsions, as ocular drug carriers.
AB  - Three different colloidal carriers, namely, nanoparticles and nanocapsules made
      of poly-epsilon-caprolactone and submicron emulsions, were designed, and their
      capacity for increasing the comeal penetration of drugs was investigated. The
      three systems differed in their inner structure and composition, but they had a
      similar size (200-250 nm) and a negative superficial charge (-16 to -42 mV).
      Indomethacin, which was used as a model drug, was dispersed at a molecular level
      within the colloidal systems, no chemical interaction between the polymer and the
      drug being detected. Release of the encapsulated indomethacin occurred very
      rapidly upon high dilution in a buffered medium and was independent of the
      composition of the system. The in vitro comeal penetration of the encapsulated
      indomethacin was more than 3-fold that of the commercial eye drops. This
      increased penetration was similar for the three formulations investigated, which
      therefore excludes the influence of the inner structure or chemical composition
      of the colloidal systems on the comeal penetration of indomethacin. Thus, it
      could be stated that the main factor responsible for the favorable comeal
      transport of indomethacin is the colloidal nature of these carriers rather than
      their inner structure or composition.

PMID- 8742947
TI  - Rheological characterization of xanthan gum and hydroxypropylmethyl cellulose
      with respect to controlled-release drug delivery.
AB  - It has been observed previously that xanthan gum (XG) and hydroxypropylmethyl
      cellulose (HPMC) show different drug release behavior. In order to clarify these
      findings, the rheological properties of both polymers have been determined by
      oscillatory as well as by steady shear measurements. Aqueous solutions of 4 and
      7% (w/w) polymer have been used to simulate the outer surface of a hydrated
      tablet. The dynamic moduli, i.e., storage modulus (G') and loss modulus (G") of
      the two polymers have been determined in pure water and USP phosphate buffer pH
      7.4 at different dilutions. In this concentration range XG solution exhibits "gel
      like" behavior, while HPMC behaves as a typical polymer solution. These findings
      are quite consistent with the reported higher ability of XG matrices to retard
      drug release than HPMC matrices for controlled-release formulation. The effects
      of differences in drug solubility and acidity, as well as the addition of
      lactose, and of the ionic strength of the medium on the rheological properties of
      XG and HPMC solutions have been studied in detail. Among these parameters, only
      the salt concentration exerts an enhancing effect on both moduli of XG, while no
      detectable influence on HPMC solution could be observed.

PMID- 8742949
TI  - Glomerulosclerosis: the final pathway is clarified, but can we deal with the
      triggers?

PMID- 8742948
TI  - Influence of activated charcoal on the disposition kinetics of methamphetamine
      enantiomers in the rat following intravenous dosing.
AB  - Methamphetamine (MAP) is a central nervous system stimulant that is widely abused
      by populations of several countries. There is no specific antidote for the
      treatment of an overdose. Activated charcoal administered orally has been used to
      enhance the systemic elimination of certain toxic substances via
      "gastrointestinal dialysis". The results of in vitro studies have shown that MAP
      can be rapidly adsorbed from solution by activated charcoal. We have evaluated
      the effect of a single oral dose of activated charcoal on the disposition
      kinetics of MAP following a short iv infusion. Male Sprague-Dawley rats were
      given an oral dose of activated charcoal (Actidose-aqua, 1 g/kg) 10 min before a
      short iv infusion of racemic MAP; whereas the control group was given an
      equivalent volume of water. Enantiomers of MAP and metabolites in serum and urine
      were analyzed by an enantiomer-specific method which employed HPLC and detection
      of a fluorescent derivative. There were no differences in any of the disposition
      parameters between the two groups. Within each group, the clearance (CLs) of l
      MAP was greater than that of d-MAP. However, there were no differences in the
      steady-state volume of distribution (Vss). The CLs (mL/(min kg)) and Vss (L/kg)
      values for l- and d-MAP in the control group were (mean +/- SD): 55.8 +/- 20.4,
      48.7 +/- 17.9, 2.64 +/- 1.16, and 2.90 +/- 1.36, respectively. The corresponding
      values in the charcoal-pretreated group were (mean +/- SD): 57.4 +/- 23.4, 51.1
      +/- 20.7, 2.79 +/- 1.32, and 2.98 +/- 1.47. These results suggest that oral
      activated charcoal does not enhance the elimination of MAP from the body.

PMID- 8742950
TI  - Prognosis of acute renal failure 1975-1995.

PMID- 8742951
TI  - Nicardipine hydrochloride suppresses DNA synthesis in human mesangial cells
      stimulated with recombinant human (rh) platelet-derived growth factor AA, rh
      interleukin-1 alpha, or rh tumor necrosis factor-alpha.
AB  - In order to define the role of cytokines in mesangial cell pathophysiology, we
      measured the mitogenic activity of recombinant human platelet-derived growth
      factor AA (rhPDGF-AA), rh interleukin-1 alpha (rhIL-1 alpha) and rh tumor
      necrosis factor-alpha (rhTNF-alpha) in cultured human mesangial cells, and
      investigated the effect of the calcium channel blocker nicardipine hydrochloride
      on their cell mitogenic activity. DNA synthesis in mesangial cells, stimulated by
      rhPDGF-AA, rhIL-1 alpha or rhTNF-alpha, was measured using [3H]TdR up take and
      similar investigations, with nicardipine hydrochloride added to the above, were
      conducted. The results showed DNA synthesis in cultured human mesangial cells
      were stimulated by rhPDGF-AA, rhIL-1 alpha and rhTNF-alpha, and this effect was
      reduced by the addition of nicardipine hydrochloride. Since rhPDGF-AA, rhIL-1
      alpha and rhTNF-alpha are released by the inflammatory cells which infiltrate
      glomeruli, these cytokines may be involved in the mechanisms of mesangial cell
      proliferation observed in immune-mediated mesangial proliferative
      glomerulonephritis. Nicardipine hydrochloride reduced DNA synthesis in cultured
      human mesangial cells in response to these cytokines, suggesting possible
      application in medical therapy for immune-mediated mesangial proliferative
      glomerulonephritis.

PMID- 8742952
TI  - Intrarenal mRNA expression of the rat MDCK-type chloride channel.
AB  - We have reported the isolation of a rat cDNA for MDCK-type chloride channel
      (RKCL) which is expressed in many tissues including the kidney. In the present
      study, intrarenal expression distribution of RKCL mRNA and the effect of
      dehydration on its expression were examined. In situ hybridization showed that
      RKCL mRNA is more abundantly expressed in the renal medulla and papilla than in
      the cortex. Reverse transcription and polymerase chain reaction using
      microdissected nephron segments showed that RKCL mRNA is expressed in several
      nephron segments, notably the ascending thin limb of Henle's loop and inner
      medullary collecting duct. Under dehydration, renal RKCL mRNA expression level
      was not significantly changed for 5 days. In conclusion, RKCL mRNA is expressed
      in most nephron segments, playing a role in the renal tubular chloride ion
      homeostasis.

PMID- 8742953
TI  - Renal 31-phosphorus-magnetic resonance spectral changes in experimental uremia.
AB  - Altered renal cellular phosphate (Pi) homeostasis may be involved in disturbed
      regulation of 1 alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3] production in chronic
      renal failure. To assess cytoplasmic concentrations of P(i) and other phosphate
      metabolites in uremia, phosphorus-magnetic resonance spectroscopy (31P-MRS)
      studies were carried out in vivo in rat remnant kidney. Five-sixths
      nephrectomized animals (Nx, n = 8, serum creatinine 1.28 +/- 0.18 mg/ dl) and
      sham-operated control animals (n = 8) were pair-fed a high-phosphate diet (1.6%
      phosphate, 1.0% calcium) for 19 days. In both remnant and intact kidneys, 31P
      magnetic resonance spectra displayed six major peaks: phosphomonoesters (PME),
      P(i), phosphodiesters, and adenosine triphosphate (ATP)-gamma, -alpha, and -beta.
      Phosphocreatine was absent. The relative intensity of the renal gamma ATP signal
      was comparable between the remnant kidney in Nx and the sham-operated kidney in
      control animals and was, therefore, used as the internal standard to assess the
      P(i)/gamma ATP ratio. The P(i)/gamma ATP ratio was significantly (p < 0.05)
      increased in the remnant kidney as compared to the sham-operated control kidney
      (0.97 +/- 0.24 in Nx vs. 0.75 +/- 0.12 in sham-operated controls; means +/- SE).
      Similarly, the PME/gamma ATP ratio was significantly increased in Nx (p < 0.01),
      whereas the relative intensities of other phosphate metabolite signals were not
      altered in Nx. Mean serum 1,25(OH)2D3 concentrations were 62 pg/ml for Nx and 93
      for sham-operated controls (p < 0.05); mean serum phosphate levels were 4.35
      mmol/l for Nx and 2.61 for sham-operated controls (p < 0.01). The pH in the
      remnant kidneys was 7.20 +/- 0.06 (mean +/- SE, n = 8), whereas the pH in intact
      kidneys was 7.29 +/- 0.05 (n = 8, p < 0.05). To examine the contribution of blood
      cells to 31P-magnetic resonance spectra, an exchange transfusion with a
      fluorocarbonated oxygen carrier (to a final hematocrit of 8%) was carried out,
      while animals (n = 5) were monitored by MRS. This did not significantly change
      the relative intensities of phosphate metabolite peaks, indicating that blood
      phosphorus did not measurably contribute to the renal P(i) signal. The data
      suggest that intrarenal P(i) concentration is elevated in renal failure. This
      could inhibit 25-hydroxyvitamin D3-1 alpha-hydroxylase activity and thus have
      some relevance for pathogenesis of renal hyperparathyroidism.

PMID- 8742954
TI  - Renal denervation prevents intraglomerular platelet aggregation and glomerular
      injury induced by chronic inhibition of nitric oxide synthesis.
AB  - Nitric oxide (NO) inhibits platelet adhesion and aggregation in vitro. In vivo,
      chronic inhibition of NO synthesis induces nephrosclerosis and hypertension.
      Although the pathophysiological mechanism of this glomerular injury has not been
      clarified, sympathetic nerve activation, a potent procoagulant stimulus elicited
      by NO inhibition, may play a role. To investigate the role of renal sympathetic
      nerves in the development of renal injury induced by NG-nitro-L-arginine methyl
      ester (L-NAME), a specific NO synthesis inhibitor, we examined renal histological
      changes in four groups of Sprague-Dawley rats: (1) sham operated, vehicle
      treated; (2) sham operated, L-NAME treated; (3) denervated, vehicle treated, and
      (4) denervated, L-NAME treated. Following renal denervation or sham operation, L
      NAME was administered orally for 4 weeks. Chronic NO inhibition induced platelet
      aggregation and erythrocyte stasis in the glomerular capillary lumen accompanied
      by electron-microscopic glomerular injury. Renal denervation abrogated platelet
      aggregation and glomerular injury in L-NAME-treated animals. Thus, chronic NO
      synthesis inhibition induced intraglomerular platelet aggregation and glomerular
      injury, which was attenuated by renal nerve denervation. These results suggest
      that intrinsic NO may have an antithrombotic effect in the glomeruli and may play
      a protective role in the progression of glomerular injury possibly mediated by
      renal sympathetic nerves.

PMID- 8742955
TI  - Effect of amino acids on the excretions of purine bases and oxypurinol.
AB  - To investigate whether or not amino acids affect the urinary excretion of purine
      bases and oxypurinol, a 12% amino acid solution was infused to 6 subjects who
      took allopurinol (300 mg) 6 h before the study. Amino acid infusion increased the
      urinary excretion and the fractional clearance of uric acid and oxypurinol and
      decreased the plasma concentration of oxypurinol. However, it affected neither
      the urinary excretion, the fractional clearance, the plasma concentration of
      oxypurines nor the plasma concentration of uric acid. These results indicate that
      amino acids affect the renal transport pathways of oxypurinol and uric acid but
      not those of oxypurines. In addition, it was suggested that the amino acid
      induced increase in the urinary excretion of oxypurinol may be considered when
      allopurinol is administered to hyperuricemic patients with hypoproteinemia who
      have taken amino acids either orally or intravenously.

PMID- 8742956
TI  - Effect of hemodialysis on peripheral glucose metabolism of patients with chronic
      renal failure.
AB  - Glucose intolerance has been shown in patients with chronic renal failure (CRF),
      probably associated with insulin resistance in peripheral tissues. The present
      study was thus designed to investigate the effect of hemodialysis on peripheral
      muscle glucose metabolism of patients with CRF. Nine normal subjects and 6
      patients with CRF were studied after an overnight fast (12-14 h) and during 3 h
      after ingestion of 75 g of glucose. Peripheral glucose metabolism was analyzed by
      the forearm technique to estimate the muscle exchange of substrates combined with
      indirect calorimetry. The CRF patients were studied before and after at least 1
      month of hemodialysis treatment. Plasma glucose levels (arterial and venous) were
      higher in uremic patients before dialysis than in normal controls. After the
      dialysis therapy there was improvement in the glycemic profile of the CRF
      patients. Decreased forearm muscle glucose uptake was observed in the uremic
      patients before dialysis compared to the normal subjects (234 +/- 71 vs. 858 +/-
      52 mumol/100 ml forearm . 3 h, p < 0.05) with diminished nonoxidative glucose
      metabolism (128 +/- 78 vs. 686 +/- 58 mumol/100 ml forearm . 3 h, p < 0.05).
      After the hemodialysis treatment of the CRF patients, the forearm glucose uptake
      and the nonoxidative glucose metabolism increased significantly to values of 527
      +/- 64 and 384 +/- 87 mumol/100 ml forearm . 3 h, respectively. Muscle glucose
      oxidation did not differ significantly between normals and CRF patients before
      and after dialysis, as well as the serum insulin levels. These data demonstrate
      that insulin resistance in the presence of chronic uremia is accompanied by
      impaired muscle glucose uptake and nonoxidative glucose metabolism, which are
      significantly improved by the hemodialysis treatment.

PMID- 8742957
TI  - Effect of rHuEpo therapy in dialysis patients on endogenous erythropoietin
      synthesis after renal transplantation.
AB  - We have undertaken a prospective study to examine the effect of recombinant human
      erythropoietin (rHuEpo) therapy during dialysis on Epo levels after renal
      transplantation and to evaluate the impact of this therapy on the immediate graft
      function. Between December 1991 and December 1993, 91 renal transplant recipients
      were studied. There were 34 females and 57 males and the mean age was 38 years.
      Forty-two patients were treated during dialysis with rHuEpo due to anemia and 49
      patients did not receive it. Endogenous Epo (eEpo), hemoglobin concentration,
      hematocrit level and serum creatinine were determined on days 0, 2, 4, 8, 15, 30,
      60 and 180 after transplantation. Ferritin level was determined pretransplant and
      on day 60. RESULTS: Patients not treated with rHuEpo during dialysis experienced
      a transient increase in endogenous Epo after renal transplant that was not
      observed in treated patients (26 +/- 3.3 vs. 9 +/- 1.5 mU/ml, p < 0.001). The
      eEpo peak was similar in patients with early or delayed graft function (23 +/-
      4.3 vs. 32 +/- 5.4 mU/ml, NS). The recovery of the anemia after a successful
      renal transplant took place in patients treated as well as those not treated with
      rHuEpo without significant differences. In the treated group, the pretransplant
      hematocrit level was similar in patients with early or delayed graft function (31
      +/- 3.5% vs. 32 +/- 4.8%), but in the untreated group, the hematocrit level was
      lower in patients with early renal function (28.5 +/- 4% vs. 32 +/- 3%, p <
      0.05). However, these patients also had a significantly shorter warm ischemia
      time (53 +/- 13.8 vs. 64 +/- 14.5 min). Fifty-two percent of the rHuEpo-treated
      patients and 36% of the untreated patients had delayed graft function. In
      conclusion, different courses of eEpo levels after renal transplant were observed
      depending on whether or not patients had been treated with rHuEpo during
      dialysis. Untreated patients experienced a transient increase which was not
      observed in the treated group. Immediate or delayed graft function did not modify
      eEpo levels. No association was found between rHuEpo therapy during dialysis and
      delayed graft function.

PMID- 8742958
TI  - Frequency of complications with prolonged femoral vein catheterization for
      hemodialysis access.
AB  - Analysis of 120 cases of femoral vein catheterization for > or = 2 days for
      hemodialysis in 89 hospitalized patients was performed to determine the frequency
      of catheter-related complications including infection and venous thrombosis. The
      rate of clinically significant complications was < 3.5% and compared favorably
      with published complication rates of central vein catheters. We conclude that
      prolonged femoral vein catheterization for hemodialysis is associated with an
      acceptably low rate of complications when appropriate techniques for placement
      and catheter care are followed and should be considered a reasonable option for
      vascular access in hospitalized patients.

PMID- 8742959
TI  - Effect of elevated calcium levels on segmental tubular sodium reabsorption in
      normal man.
AB  - The aim of the present study was to assess the effect of calcium infusion on
      segmental tubular reabsorption in humans using lithium clearance, along with
      creatinine and free water clearances during maximal water diuresis. In 8 healthy
      volunteers, a 20-min 5 mg/kg calcium infusion that increased serum calcium levels
      from 2.27 +/- 0.07 to 2.87 +/- 0.07 mmol/l (p < 0.01) was followed by a 60-min 3
      mg/kg infusion for maintenance. During the experimental period, blood pressure
      did not change. Maximal urine flow increased from 15.6 +/- 2.4 to 20.8 +/- 2.8
      ml/min (p < 0.01), while clearance of sodium increased from 1.5 +/- 0.4 to 3.7 +/
      0.9 ml/min (p < 0.001). Lithium clearance showed an increase of 7.4 ml/min,
      pointing to a suppression of proximal reabsorption. Free water clearance also
      increased from 11.5 +/- 3.7 to 14.4 +/- 3.9 ml/min, indicating an increase in
      TALH reabsorption which was attributed to increased sodium and water reaching
      this segment. Time control studies showed no significant changes in the
      parameters measured except for potassium excretion. Potassium excretion during
      calcium infusion was somewhat lower than during the control studies. The data
      support the view that an increase in serum calcium concentration leads to a
      decrease in proximal tubular reabsorption as indicated by lithium clearance while
      a decrease in reabsorption in the collecting duct could well add to the diuretic
      properties of calcium.

PMID- 8742960
TI  - Role of secondary hyperparathyroidism in the development of post-transplant acute
      tubular necrosis.
AB  - Post-transplant cure tubular necrosis (ATN) represents the most frequent cause of
      delayed graft function in the immediate post-transplant period. Several causes
      have been associated with the development of post-transplant ATN such as donor
      and recipient ages, cold-warm ischemia times, HLA mismatches, and postoperative
      hypotension. In the present study, we retrospectively evaluated the role of
      secondary hyperparathyroidism and high parathyroid hormone (PTHi) blood levels in
      the development of post-transplant ATN. One hundred patients submitted to
      cadaveric renal transplant between January 1992 and March 1993 in our unit were
      included. Twenty-seven patients (27%) developed post-transplant ATN and seventy
      three (73%) did not. Post-transplant ATN was significantly associated with gender
      (p < 0.01), recipient age (p < 0.01), number of transplantations (p < 0.01), time
      on hemodialysis (p < 0.001), cold ischemic time (p < 0.05) and PTHi levels (p <
      0.001). The bivariate and multivariate statistical analyses demonstrated that the
      development of post-transplant ATN was significantly more frequent in females;
      retransplanted patients, patients with a time on dialysis of more than 5 years,
      recipients over 60 years old, patients with a PTHi blood level higher than 240
      pg/ml (4 times normal level) and a cold ischemia time of more than 18 h. Based on
      these results, we conclude that high PTHi blood levels in the renal transplant
      recipients represent a relevant factor in the development of post-transplant ATN.
      The administration of intravenous pulsed of 1,25(OH)2D3 and/or a calcium channel
      blocker in the perioperative period could be useful to decrease the incidence and
      severity of post-transplant ATN in these patients.

PMID- 8742961
TI  - Magnetic resonance angiography as a technique for the visualization of
      hemodialysis shunts.
AB  - In order to test the suitability of magnetic resonance angiography for the
      visualization of Brescia-Cimino hemodialysis shunts, 20 patients (8 women, 12
      men, aged 24-69 years) were examined with this technique. The shunt arm was
      placed in an extremity coil. The time-of-flight method was applied. Examination
      time was less than 15 min. Arterial digital subtraction angiography (DSA) of the
      shunt arm was carried out additionally in 8 patients in whom pathological results
      had been obtained. Surgery was performed on 2 patients. In all cases, the feeding
      artery, anastomosis, and shunt were clearly visible. The results corresponded
      exactly to those of DSA and, in the patients who had undergone surgery, also to
      the situs. The patients stated that the examination technique was not very
      disturbing. Magnetic resonance angiography in the time-of-flight technique seems
      to be recommendable for the examination of Brescia-Cimino dialysis shunts.
      Compared to DSA, it has major advantages: it is noninvasive, and no ionizing
      radiation or contrast medium are associated with the procedure.

PMID- 8742963
TI  - Primary bilateral renal centrocytic non-Hodgkin's lymphoma as a cause of renal
      failure.
AB  - We present a patient whose cause of renal failure was primary and isolated
      bilateral renal manifestation of centrocytic non-Hodgkin's lymphoma. The
      treatment options for bilateral primary renal lymphoma are discussed against the
      background of published data concerning this topic.

PMID- 8742962
TI  - A case of renovascular hypertension with marked polyuria after percutaneous
      transluminal renal angioplasty.
AB  - A 43-year-old female patient with hypertension was diagnosed as having one-kidney
      renovascular hypertension with dysfunction of the contralateral kidney, and
      percutaneous transluminal renal angioplasty was carried out. Marked polyuria was
      observed during the 2- to 72-hour postoperative period. During the 12- to 18-hour
      period of polyuria, the urine volume was 8.9 liters/6 h, which was 62% of the
      glomerular filtration, and was accompanied by high fractional excretion of sodium
      and of potassium and a high urine beta 2-microglobulin level. The mechanism of
      polyuria in this case is discussed.

PMID- 8742964
TI  - Plasma thrombomodulin: usefulness as a blood access failure marker in
      hemodialysis patients.
AB  - In 144 patients on hemodialysis (76 males and 68 females, median age 55.7 +/-
      14.1 years, mean period on dialysis 44.1 +/- 33.3 months), thrombomodulin was
      determined by enzyme immunoassay prior to initiation of hemodialysis. The results
      showed that the mean thrombomodulin value of hemodialysis patients was 13.59 +/-
      3.63 ng/ml which was significantly higher than the control value (3.20 +/- 0.90
      ng/ml). The thrombomodulin values were significantly higher in patients with
      blood access failure (15.27 +/- 4.45 ng/ml) than in those without (13.11 +/- 3.31
      ng/ml), and the rate of blood access failures was also significantly higher in
      those with thrombomodulin values of 15.0 ng/ml or higher than in those with
      values < 15.0 ng/ml. It was evident that there is a higher risk of blood access
      failure in patients with severe systemic vascular endothelial injury, and
      thrombomodulin is a useful marker of such an injury.

PMID- 8742965
TI  - Association between type II cryoglobulinemia and hepatitis C virus in a case
      treated with interferon-alpha.

PMID- 8742966
TI  - NG-nitro-L-arginine methyl ester causes glomerular nitrite production in long
      term incubations.

PMID- 8742967
TI  - The association between chronic renal disease and cone-shaped epiphyses in
      children.

PMID- 8742968
TI  - IgA nephropathy, consanguinity and hypertension.

PMID- 8742969
TI  - Lipoprotein(a) levels and fibrinolytic activity in patients with nephrotic
      syndrome.

PMID- 8742970
TI  - Better transmitral flow in hypertensives in comparison to normotensive patients
      with well functioning kidney transplant.

PMID- 8742971
TI  - Comparison of aminophylline and insulin infusions in treatment of hyperkalemia in
      patients with end-stage renal disease.

PMID- 8742972
TI  - Organ trading: a medical or ethical mistake?

PMID- 8742973
TI  - Rapidly progressive fibrillary glomerulonephritis and cutaneous T-cell lymphoma.

PMID- 8742974
TI  - Hepatitis C: is isolation essential?

PMID- 8742975
TI  - Transmission of hepatitis C virus by transfer of an infected individual to a new
      dialysis unit.

PMID- 8742976
TI  - Renal amyloidosis complicating Takayasu's arteritis: a case report.

PMID- 8742977
TI  - Effect of angiotensin-converting enzyme inhibitors on anemia in hemodialyzed
      patients.

PMID- 8742978
TI  - Changes of T-lymphocyte subsets in patients with hemorrhagic fever with renal
      syndrome.

PMID- 8742979
TI  - Immunohistochemical localization of beta 2-microglobulin and advanced glycation
      end products in amyloid-enriched carpal tunnel ligament.

PMID- 8742980
TI  - Recurrence of thyrotoxicosis during hemodialytic treatment in a patient with
      chronic renal failure.

PMID- 8742981
TI  - Methylprednisolone pulse therapy for severe absorption fever due to perirenal
      hematoma after percutaneous renal biopsy.

PMID- 8742982
TI  - Furosemide-albumin complexes in refractory nephrotic syndrome and chronic renal
      failure.

PMID- 8742983
TI  - Development of multiple myeloma in 2 patients with chronic pyelonephritis and
      long-term hemodialysis treatment.

PMID- 8742985
TI  - Evoked potential (EP) alterations in experimental allergic encephalomyelitis
      (EAE): early delays and latency reductions without plaques.
AB  - Experimental allergic encephalomyelitis (EAE) in its chronic relapsing (CR-EAE),
      chronic progressive (CP-EAE) and acute (A-EAE) forms was obtained in 24 juvenile
      strain 13 guinea pigs. Visual, brainstem acoustic and somatosensory evoked
      potentials (EPs) were recorded in these animals prior to the sensitizing
      injection and during the course of the disease. Delays in the EPs appeared 15
      days post-sensitization (dps), preceding or simultaneously with clinical
      alterations: electron microscopy revealed myelin stripping and vacuolation in the
      animals sacrificed 25 dps. Decreases in EP latency were recorded 32 dps; when
      electron microscopy revealed myelin layers indicating remyelination, whereas
      light microscopy showed only inflammatory changes. When confluent plaques were
      revealed by light microscopy 120 dps, the EP wave shapes were distorted or
      absent. The discussion reviews the literature on early myelin and conduction
      changes during central demyelination.

PMID- 8742986
TI  - Long time echo STIR sequence magnetic resonance imaging of optic nerves in optic
      neuritis.
AB  - Magnetic resonance images of optic nerves were obtained in 20 patients with acute
      optic neuritis (ON), and assessed by means of clinical, visual field and visual
      evoked potential evaluations; the imaging was repeated 1 year later. The results
      of the conventional Short Tau Inversion Recovery (STIR) sequence obtained using
      short time echo (STE-STIR: 22 msec) were compared with those of the long time
      echo sequence (LTE-STIR: 80 msec). The conventional STE-STIR sequence revealed
      lesions in 57.2% cases of acute ON and in 42.9% of the optic nerves affected by
      previous ON; the LTE-STIR sequence was diagnostic in 95.2% of acute ON cases and
      in 85% of patients with previous ON. The calculated length of the optic nerve
      lesions was significantly longer in the images obtained using the LTE-STIR
      sequence than in those obtained using conventional STE-STIR sequences.

PMID- 8742984
TI  - Thrombolytic therapy. From myocardial to cerebral infarction. The MAST-I Group.
      Multicentre Acute Stroke Trial.
AB  - Thrombolysis is proposed for the acute treatment of cerebral infarction as it is
      able to recanalize occluded arteries and thus potentially restore normal
      perfusion of the cerebral parenchyma, but the results concerning the efficacy of
      this treatment are still inconclusive. However, it has been fully demonstrated
      that thrombolytic treatment, leads to a significant reduction in mortality, in
      patients with acute myocardial infarction. Data from all of the pilot studies
      using SK or tPA treatment in acute stroke are described in this review, which
      underlines the incidence of hemorrhagic transformation (hemorrhagic infart and
      parenchymal hematoma) and its possible correlation to clinical worsening.
      Pharmacological, experimental and clinical studies encourage the carrying out of
      large-scale clinical trials using thrombolytics in patients with acute cerebral
      infarction. Significant data relating to ongoing controlled clinical trials will
      be available in the near future; only after the analysis of these results will it
      be possible to confirm the efficacy of thrombolytics in acute stroke.

PMID- 8742987
TI  - Are VEP abnormalities in optic neuritis (ON) dependent on plaque size? A
      reappraisal of the physiopathology of ON based on improved MRI and multiple-lead
      recordings.
AB  - Twenty patients with optic neuritis (ON) described in the previous study [23]
      underwent serial VEP recordings (using multiple electrode arrays) for two years.
      The VEPs could be correlated with the lesions revealed by MRI, Visual Field tests
      and other clinical findings. On the basis of their scalp distribution, they were
      classified as "really delayed" VEPs and "pseudo-delayed" VEPs. Real delays could
      be recorded at the onset of ON or shortly afterwards, and their appearance
      indicated the recovery of visual function and a good prognosis. Pseudo-delays
      indicated an alteration in the visual field and, unless a breakthrough of normal
      or delayed components appeared in the first three months, following acute ON,
      indicate a poor prognosis for the recovery of visual function. The pseudo-delayed
      VEPs were mainly observed in patients with longer lesions revealed by means of
      LTE-STIR MRI [23]; there was no correlation between VEP latency and the length of
      plaques. Our findings contradict previous theories on the timing of conduction
      alterations in ON and multiple sclerosis.

PMID- 8742988
TI  - Cerebral haemodynamic changes induced by spinal cord stimulation in man.
AB  - Spinal cord stimulation (SCS) has been shown to influence cerebral perfusion in
      both experimental models and humans. With the aim of further verifying such an
      effect, twelve patients had an epidural (cervical or dorsal) lead inserted
      percutaneously and underwent regional cerebral blood flow (rCBF) examinations
      (133-Xenon inhalation method) before and during SCS. Mean blood velocity (MBV) in
      the middle cerebral artery was also measured in seven cases by means of
      transcranial Doppler. In the patients with a cervical lead, a symmetrical
      increase in rCBF was found, mainly in the anterior regions (from +8% to +21%).
      MBV increased in four cervical lead implants (from +16% to +20%) and in one case
      with a dorsal lead (+15%). These results suggest that cerebral perfusion may
      increase in patients undergoing SCS through a cervical lead. Although the
      mechanism involved in the increase in rCBF remains to be clarified, frontal lobe
      functional activation by the ascending reticular pathways through the thalamo
      cortical projections might be hypothesised.

PMID- 8742989
TI  - Clinical and hormonal aspects of male hypogonadism in myotonic dystrophy.
AB  - In order to study male hypergonadotropic hypogonadism as completely as possible,
      and to evaluate its possible effects on muscle atrophy and sexuality, RIA or IRMA
      methods were used to measure the levels of luteinizing hormone (LH), follicle
      stimulating hormone (FSH), prolactin, total (T) and free (FT) testosterone,
      estradiol (E), dihydrotestosterone (DHT), sex hormone binding globulin (SHBG),
      androstenedione (A) and 17-OH-progesterone (17-OH-P) in 29 patients with myotonic
      dystrophy (MD). The mean hormonal levels +/-SD were: LH 8.0 +/- 4.4 mIU/ml, FSH
      17.4 +/- 11.5 mIU/ml, A 200 +/- 130 ng/dl (all higher than in controls); T 406 +/
      290 ng/dl, FT 22.7 +/- 7.0 pg/ml, DHT 55.5 +/- 29.7 ng/ml (all lower than in
      controls). The low FT and DHT levels (never previously studied in MD) confirm the
      androgenic deficiency. The high androstenedione levels and low testosterone
      concentrations suggest defective enzyme 17-dehydrogenase. The duration of the
      disease correlated with both testosterone (r = -0.56) and FT levels (r = -0.59),
      showing that hypogonadism tends to worsen progressively. When the patients were
      divided into three groups on the basis of the severity of muscle involvement (A,
      B and C), LH and FSH levels were higher in group C (more severe disease) than in
      group A, respectively 9.3 +/- 4.7 and 20.6 +/- 12.3 mIU/ml versus 4.8 +/- 0.9 and
      8.4 +/- 3.8, p < 0.03; T levels were lower in group C than in group A, 337.3 +/-
      263.4 ng/dl versus 649.7 +/- 320.3 (p < 0.03); however, there was no significant
      difference in the FT levels of the three groups, which may imply that
      hypogonadism is unlikely to have a direct effect on muscle atrophy. About 25% of
      our patients were impotent; these subjects had higher LH and FSH (p < 0.001) and
      lower FT levels than the patients who were not impotent (p < 0.03). However,
      hypogonadism may not be the only cause of impotence as all of the impotent
      patients belonged to group C and had a very high (CTG)n triplet expansion. We
      hypothesise that hypogonadism and sexual impairment could be partially due to a
      muscle cell alteration: i.e. a dysfunction of both the testicular peritubular
      myoid cells and of the corpus cavernosum smooth muscle.

PMID- 8742990
TI  - Sexual function in multiple sclerosis. A 5-year follow-up study.
AB  - Sexual dysfunction is known to occur in multiple sclerosis (MS). The purpose of
      the study is to describe the change in sexual function and symptoms in a
      longitudinal study. Forty-nine patients (27 females, 22 males) with definite MS
      were interviewed and examined with 5 years interval. The number of patients with
      sexual dysfunction increased significantly (p = 0.009) and involved females and
      males equally. Males usually had 1 or two symptoms of sexual dysfunction, while
      females frequently had 2 or more symptoms. It is concluded that the risk of
      sexual dysfunction increases over time. Further studies in treatment
      possibilities are needed.

PMID- 8742991
TI  - Acute generalized dystonia due to a bilateral lesion of basal ganglia mainly
      affecting the nuclei pallidi.
AB  - We describe a case of acute generalized dystonia due to bilateral damage to the
      basal ganglia, mainly affecting the globi pallidi. The lesion was probably
      related to a hypoxic condition following a heroin injection. Therapy with
      pimozide almost completely controlled the dystonia.

PMID- 8742992
TI  - Microembolization from a carotid mural thrombus detected by transcranial Doppler.
AB  - Over the last few years, many authors have described the possibility of using
      transcranial Doppler to demonstrate the passage of microemboli in the cerebral
      arteries. We report the case of a 44-year-old woman with thrombotic diathesis and
      thrombocytosis who was admitted twice within a short period of time (one and a
      half months) to a neurological department because of multiple cerebral
      infarctions. On the occasion of the second admission, a colour-Doppler
      examination of the epiaortic vessels, which had previously been negative, showed
      a carotid lesion due to a mural thrombus and, on the same side as the carotid
      lesion, transcranial Doppler detected short-duration, high-intensity signals in
      the middle and anterior cerebral arteries, an expression of the passage of
      microemboli. As already described by other authors in similar clinical
      situations, our case confirms that transcranial Doppler can identify the passage
      of microemboli in the circle of Willis.

PMID- 8742993
TI  - Intracranial meningioma at the site of a previous cranial fracture: case report
      and review of the literature.
AB  - The authors present a case of post-traumatic intracranial meningioma, selected
      according to the criteria specified in the relevant literature. Assessment of the
      clinical characteristics of our patient and those reported in the literature
      seems to confirm that, in some cases, head trauma may be a factor contributing to
      the development of meningioma.

PMID- 8742994
TI  - Ganglionic cyst of the deep peroneal nerve: description of a case.
AB  - The case of a patient with a small intraneural ganglion of the deep peroneal
      nerve is described, including the clinical and electrophysiological
      characteristics and the course four years after surgery.

PMID- 8742995
TI  - Disseminated encephalitis following streptococcal infection.
AB  - Various neurological disorders have been related to Streptococcus pyogenes
      infection. Only recently, and for the first time, it has been suggested that
      acute disseminated encephalitis may also complicate a streptococcal infection.
      The case reported in this paper seems to confirm this hypothesis.

PMID- 8742996
TI  - The uncertain boundaries between neurology and psychiatry.

PMID- 8742997
TI  - The society journal.

PMID- 8742998
TI  - The importance and state of medical and public health research related to vision
      in Australia.

PMID- 8742999
TI  - Sporadic Leber hereditary optic neuropathy in Australia and New Zealand.
AB  - BACKGROUND: Leber hereditary optic neuropathy (LHON) is one of the more common
      forms of hereditary optic neuropathy and one of the few mitochondrial
      neuropathies. Prior to the advent of molecular DNA testing, the diagnosis
      depended on the recognition of typical fundal changes, as well as a family
      history of maternal transmission. Sporadic cases were therefore diagnosed with a
      level of uncertainty. The aim of this study is to identify the proportion of
      patients with idiopathic bilateral optic neuropathy/atrophy who are suffering
      from LHON. METHODS: Requests were sent to all ophthalmologists and neurologist in
      Australia and New Zealand for blood or hair follicle samples of patients with
      diagnosis of bilateral optic neuropathy/atrophy of uncertain aetiology for DNA
      testing by restriction endonuclease analysis. RESULTS: One hundred and forty-four
      samples were received, of which 96 were sporadic cases of idiopathic optic
      atrophy. Eleven of these sporadic patients were found to harbour pathogenetic
      mitochondrial point mutations associated with LHON. CONCLUSIONS: Our results
      indicated that 11% of patients with bilateral optic neuropathy/atrophy of
      uncertain aetiology are suffering from LHON. Comparing this data with all the
      known familial cases of LHON, we report that at least 8% of all LHON cases in
      Australia are sporadic. We concluded that mtDNA testing for LHON in patients with
      idiopathic optic atrophy should be included in the initial laboratory work-up.

PMID- 8743000
TI  - Prophylactic perifoveal laser treatment of soft drusen.
AB  - PURPOSE: To assess the efficacy and safety of perifoveal laser to cause drusen to
      resorb, and establish a treatment protocol. METHODS: Treatment technique was
      determined by the outcome in one patient with 15-year follow-up. In an
      uncontrolled series a perifoveal ring of gentle laser was applied to 30 eyes of
      28 patients, 18 with bilateral drusen and 10 with exudative disease in the fellow
      eye. Comparison was made between treated and untreated eyes in 14 patients with
      bilateral drusen. Mean follow-up was 16.8 months (range, three to 42 months).
      RESULTS: Soft drusen resorbed in all treated eyes in the vicinity of laser and
      within the fovea. Large soft confluent drusen (> 500 microns) responded most
      rapidly. Visual acuity improved one or more lines in 12 (40%) treated eyes, was
      unchanged in 16 (53%) and deteriorated in two (7%). In 14 patients with bilateral
      drusen in whom only one eye was treated, VA remained unchanged in 10 eyes and
      improved in four treated eyes while none of the untreated eyes improved (P =
      0.03, chi 2) and decreased in four eyes. Atrophic expansion of laser burns was
      minimal. CNV developed in two of 30 eyes (7%). CONCLUSION: Perifoveal laser
      treatment appears to expedite the regression of soft drusen within the fovea. The
      risks of complications may be reduced by treating eyes early, before pigment
      changes develop and by applying a minimum number of burns at a distance greater
      than 750 microns from the foveal centre. Treatment should currently be
      administered only in the context of a prospective clinical trial, which is
      required to assess whether this treatment results in lowered risk of visual loss
      from CNV or geographic atrophy.

PMID- 8743001
TI  - Corneal topographic lagoons: a potential new marker for post-traumatic recurrent
      corneal erosion syndrome.
AB  - BACKGROUND: Post-traumatic recurrent corneal erosion syndrome is a common
      clinical problem in which a definitive diagnosis is not always possible based
      solely upon biomicroscopic corneal signs. Indeed, in some cases archetypical
      symptoms or a preceding history of epithelial trauma cannot always be elucidated.
      METHODS: Four groups of patients underwent corneal analysis using computer
      videokeratography. Group 1 (n = 11), subjects who presented with simple corneal
      epithelial trauma approximately three months before the study. Group 2 (n = 11),
      prospective analysis of subjects presenting with simple corneal epithelial
      trauma. Group 3 (n = 12), prospective analysis subjects with an established
      diagnosis of post-traumatic recurrent erosion syndrome. Group 4 (n = 135),
      prospective analysis of healthy control subjects. RESULTS: Small, well delineated
      areas (1.0 to 1.5 mm in diameter) of markedly reduced corneal dioptric power
      (greater than 2 dioptres), which we have termed 'corneal topographic lagoons',
      were identified more commonly in eyes with recurrent corneal erosion syndrome and
      in eyes that had recently sustained corneal epithelial trauma; being found in
      18.2% of Group 1, 9.1% of Group 2, 58.3% of Group 3 but only 1.5% of Group 4
      (control). CONCLUSIONS: The identification of areas of focal abnormality in the
      corneas of patients with post-traumatic recurrent corneal erosion syndrome
      remains a significant clinical problem. Corneal topographic analysis has
      demonstrated a focal abnormality, the 'corneal topographic lagoon', which is much
      more prevalent in cases of recent corneal trauma and recurrent corneal erosion
      syndrome than in the 'normal' population. Computerised videokeratography
      therefore adds a new tool to the armamentarium of the clinician seeking to
      identify and locate abnormalities in these difficult cases.

PMID- 8743002
TI  - Trabeculectomy and manual clot evacuation in traumatic hyphaema with corneal
      blood staining.
AB  - BACKGROUND: The management of traumatic hyphaema with raised intraocular pressure
      and corneal blood staining is difficult. Residual blood clots after anterior
      chamber washout are responsible for sustained postoperative elevation of
      intraocular pressure, even after trabeculectomy and clot evacuation. METHODS:
      Thirty-five patients with traumatic hyphaema, elevated intraocular pressure and
      varying degrees of corneal blood staining underwent a combined trabeculectomy
      with manual clot evacuation from the anterior chamber in a general hospital.
      RESULTS: The postoperative control of intraocular pressure was found to be
      adequate in all patients at the end of two months. Examination of the posterior
      segment was made possible earlier. Although the procedure is more complex, no
      significant complications were encountered. CONCLUSION: In patients presenting
      with traumatic hyphaema, secondary glaucoma and corneal blood staining,
      trabeculectomy with manual extraction of the clot through a large incision
      appears to be a safe and reliable procedure where medical therapy fails to
      control the intraocular pressure.

PMID- 8743003
TI  - A controlled clinical trial of dorzolamide: a single-centre subset of a
      multicentre study.
AB  - PURPOSE: To assess the safety and intraocular pressure (IOP)-lowering activity of
      2% dorzolamide (topical carbonic anhydrase inhibitor), compared to 0.5% timolol
      and 0.5% betaxolol eyedrops. METHODS: A parallel, masked, randomised one-year
      clinical trial was conducted in 16 patients with open-angle glaucoma or ocular
      hypertension, being a subset of a multicentre study which enrolled 523 subjects.
      Patients had IOP > 22 mmHg in one eye at baseline following washout of ocular
      hypotensive medications and were then randomised in a 3:1:1 ratio to receive 2%
      dorzolamide thrice daily, 0.5% timolol twice daily or 0.5% betaxolol twice daily
      respectively. IOP was measured at Hour 2 (morning peak), Hour 5 and Hour 8
      (afternoon trough for dorzolamide) at baseline, Weeks 2 and 4 and Months 2, 3, 6,
      9 and 12. RESULTS: Topical dorzolamide 2% solution was well tolerated and safe.
      Mean IOP for dorzolamide at Hour 2 was 29.1 mmHg at baseline and 20.8 mmHg on
      treatment at one year, a 28.5% change. Mean IOP for dorzolamide at Hour 8 was
      24.5 mmHg at baseline and 20.2 mmHg on treatment at one year, a 17.6% change.
      Comparable percent changes for timolol and betaxolol were 43.2/25.7 mmHg at Hour
      2 and 21.9/13.5 mmHg at Hour 8 respectively. CONCLUSIONS: Dozolamide 2% given
      thrice daily was well tolerated and safe, with a clinically significant effect on
      IOP comparable to betaxolol 0.5% twice daily, but not as great as timolol 0.5%
      twice daily.

PMID- 8743004
TI  - Inadvertent perforation of the globe during regional anaesthesia.
AB  - PURPOSE: This retrospective study was undertaken to review the clinical signs and
      management of patients with perforating eye injuries associated with regional
      anaesthesia for ophthalmic surgery. METHODS: Fifteen consecutive patients
      presenting with inadvertent perforation of the globe were evaluated. Eleven
      required vitreoretinal surgery. The indications were retinal detachment (six
      eyes), vitreous haemorrhage (four) and an epiretinal membrane (one eye). RESULTS:
      Those eyes with retinal detachments generally had a poor functional outcome in
      spite of the retinae being attached in five of the six eyes. The operative
      findings of those eyes with vitreous haemorrhage but attached retina demonstrated
      varying retinal tear configurations. CONCLUSIONS: Eyes with perforating injuries
      following intraorbital anaesthesia are at risk of developing a retinal
      detachment. In those eyes presenting with dense vitreous but attached retina,
      consideration of vitrectomy and laser photocoagulation is advised.

PMID- 8743005
TI  - Vision testing in atrophic macular degeneration.
AB  - PURPOSE: To determine the correlation between a group of vision tests in atrophic
      macular degeneration (AMD) in an office setting. METHODS: Patients with
      documented vision loss from atrophic macular degeneration in one eye were invited
      to attend an eye clinic every three months for a series of six vision tests for
      their good eye followed by fundus photography. Modified contrast sensitivity,
      blue/yellow anomaloscopy, flicker fusion frequency, Amsler grid, and photostress
      recovery time were correlated with Snellen acuity using the Pearson correlation
      coefficient. The regression of the Snellen acuity on sex, age and the presence of
      disciform macular degeneration in the other eye was obtained using a general
      linear model. RESULTS: The correlation with Snellen acuity result was low for all
      tests. It was highest for Amsler grid abnormality (r = -0.33345) and blue/yellow
      anomaloscopy matching range (r = -0.20742), where r denotes the correlation
      coefficient. Patient age was strongly correlated with Snellen results (P =
      0.0001), but it was not significantly related to sex (P = 0.1187) or the presence
      of disciform macular degeneration in the other eye (P = 0.9989). The photostress
      recovery time showed enormous inter-visit variations and poor correlation with
      Snellen acuity (P = 0.0526). CONCLUSIONS: The course of AMD is routinely assessed
      by Snellen acuity and any of several additional tests. When employing a test
      battery in an office setting, a clinician needs to know the relative utility and
      correlation between the tests at his disposal. Of the tests used in this study,
      the Amsler grid was the most useful addition to the Snellen acuity at all stages
      of atrophic macular degeneration, and blue/yellow anomaloscopy was useful only in
      mild macular degeneration where Snellen acuity was 6/12 or better.

PMID- 8743006
TI  - A foveal-sparing pattern of cytomegalovirus retinitis in the acquired
      immunodeficiency syndrome.
AB  - PURPOSE: We describe the clinical course of 12 eyes of 10 patients in whom
      recurrent cytomegalovirus (CMV) retinitis exhibited a foveal-sparing pattern.
      METHODS: We retrospectively reviewed the case records and photographic charts of
      10 patients (12 eyes) with the acquired immunodeficiency syndrome (AIDS), in whom
      recurrent CMV retinitis exhibited a foveal-sparing pattern within 1500 mm of the
      foveola. RESULTS: The site of primary retinitis was temporal in 10 eyes of nine
      patients in whom it was known. The median number of recurrences up to the
      observation of foveal-sparing retinitis was two (range one to eight), and five
      patients had active CMV retinitis despite treatment for at least two continuous
      months. Once established, the median rate of progression in a non-foveal vector
      was 2.3 times faster than toward the fovea, and the median time to reduction in
      acuity to < 6/30 (or death) was 11 to 14 weeks. Three eyes of three patients
      retained 6/30 or better acuity up to death. Foveal CMV retinitis ultimately
      reduced acuity to < 6/30 in five eyes. Six eyes suffered retinal detachment,
      involving the fovea in five, and being the primary reason for acuity of < 6/30 in
      four. Four patients suffered dose-limiting toxicity. CONCLUSION: Foveal-sparing
      CMV retinitis arises in patients with recurrent CMV retinitis resistant to
      treatment ('clinically resistant'), particularly that which has arisen
      temporally. Despite its foveolar proximity, and ultimate significant loss of
      function, the pattern of progression allows for preservation of useful foveal
      vision for longer periods than would have been expected.

PMID- 8743007
TI  - AIDS and the eye. A 10-year experience.
AB  - BACKGROUND: The AIDS database at Fairfield Hospital, Melbourne, maintains
      information on eye pathology as identified by the three visiting
      ophthalmologists. Patients underwent an eye consultation: if they had ocular
      symptoms; if signs were seen on direct ophthalmoscopy by physicians; or when
      their CD4+ve cell count fell below 50/microL. The first AIDS-associated eye signs
      were identified in mid-1984. In the subsequent decade, 3257 patients in Victoria
      tested positive for HIV, and 845 of the 1123 who developed AIDS were treated at
      Fairfield Hospital. METHODS: We undertook a retrospective review of the Fairfield
      Hospital database to identify the AIDS-associated ocular problems seen. RESULTS:
      Some 723 patients had an eye consultation. In the earliest stage of HIV
      infection, minor non-specific ophthalmic involvement may occur. As the disease
      progresses, microvasculopathy (cottonwool spots and haemorrhages) appears.
      External disease also occurs such as molluscum contagiosum and Kaposi's sarcoma
      of the conjunctiva. With more suppression of the immune system, opportunistic
      infections become common, and have a considerable visual morbidity. Cerebral
      toxoplasmosis (117 patients) is only rarely associated with ocular involvement
      (three patients), but cytomegalovirus (CMV) commonly causes retinitis [204
      patients (24%)]. It has been the AIDS-defining illness in 26 patients. A majority
      had the disease confined to one eye. Mean CD4 cell count at onset is 15 +/- 5
      microL and it has been associated with a viraemia in all but two patients. Late
      complications of CMV retinitis include relapse in 41 (20%), spread to the other
      eye in 24 (12%), and retinal detachment in 30 (15%). Visual impairment follows
      from retinal destruction, optic nerve involvement, and retinal detachment.
      CONCLUSION: The ophthalmic workload from late ocular complications of AIDS is
      increasing. Newer and more effective methods of treatment are being developed.
      Ophthalmologists are becoming more aware of the need for universal precautions to
      avoid risks from this and other blood-borne infections.

PMID- 8743008
TI  - Disciform keratitis causing severe irregular astigmatism.

PMID- 8743009
TI  - Penetrating eye injury from a rigid infant pacifier.
AB  - BACKGROUND: The use of infant pacifiers (dummies) is common in Australasian
      communities and has been reported to be associated with various injuries, but to
      date ocular trauma has not been reported. CASE REPORT: A 14-month-old child
      sustained a penetrating eye injury from the infant pacifier that was in his mouth
      during a minor fall. Only a lid laceration was detected at the time. One week
      later he presented with mydriasis, heterochromia and a poor red reflex. Diagnosis
      of a penetrating eye injury was made by examination under anaesthesia, with B
      scan ultrasonography demonstrating hypotony but no retinal detachment or
      intraocular foreign body. Funduscopy revealed a small inferior vitreous
      haemorrhage. Exploration of the globe adjacent to the lid wound showed a 6 mm
      laceration through the sclera plugged with prolapsed vitreous. CONCLUSION:
      Serious ocular injury may result after a minor fall with some designs of rigid
      infant pacifiers. Heterochromia and anisocoria noted by the mother heralded more
      serious ocular injury in this case. The delay in diagnosis of this injury
      emphasizes the importance of ocular examination to exclude eye trauma when
      injuries occur around the orbit.

PMID- 8743010
TI  - Precipitous visual loss secondary to optic nerve toxoplasmosis as an unusual
      presentation of AIDS.
AB  - Life-threatening conditions requiring urgent medical treatment rarely present to
      the ophthalmologist. This case report describes a patient with precipitious
      visual loss as the primary complaint and which subsequently led to the diagnosis
      of Toxoplasmic papillitis and life-threatening cerebral involvement as an initial
      manifestation of AIDS.

PMID- 8743011
TI  - [The passive transfer by Drosophila spermatozoa of exogenous DNA molecules or
      synthetic polynucleotides into fertilizable eggs].
AB  - Experiments on mutation induction in Drosophila melanogaster by injections of
      exogenous DNAs or a synthetic polyribonucleotide solutions into the hemolymph of
      the male demonstrated that Drosophila spermatozoa were able to transfer passively
      molecules of these mutagens into fertilized eggs. This induced mutations in both
      paternal and maternal chromosomes in offspring.

PMID- 8743012
TI  - [An analysis of the DNA sequence in the region of the breakpoint of the
      T(1;2)dor(var7) translocation inducing the mosaic-type position effect in
      Drosophila melanogaster].
AB  - The sites of location of (AC/GT) minisatellite sequence were detected in 2B
      region of X-chromosome of Drosophila melanogaster. The distribution of (AC/GT)
      repeats coincided with the location of one-half of the mapped breakpoints of
      known rearrangements within this region. Analysis of sequences neighbouring the
      breakpoints of the rearrangement T(1;2)dor(var7) demonstrated that the breaks
      between two sequences of (AC/GT) repeats occurred at a distance 80 and 156 bp,
      respectively, but there were no (AC/GT) repeats in r combination directly. T-rich
      sequences 25 bp long as well as short tandem repeats were found near the
      breakpoints. The pentanucleotide repeat (CTGTT)10 is located at a distance of 660
      bp from the breakpoint. It differs by one nucleotide from the sequence of the
      GTGTT satellite attached to the 1A-2B fragment of X-chromosome as a result of
      rearrangement.

PMID- 8743013
TI  - [The role of retroelements in evolution: an analysis of the suffix element from
      the Drosophila genome].
AB  - The investigation of sequences homologous to the suffix chains from Drosophila
      genome revealed the central domain of the element homologous to 16S ribosomal
      sequence from endosymbiotic organisms. The opposite strand of the element encodes
      C-domains of reverse transcriptase enzyme in F- and Doc-elements. 19 DNA clones
      possessing PCR-amplified stretches of genomic DNA were sequenced. It was found
      that micro-satellite sequences (CAACA)n/(TGTTG)n and (TTTGT)n/(CACAAA)n are the
      target sites for the insertions of suffix copies in heterochromatic regions of
      Drosophila genome in both orientations. It was found that the presence of
      decanucleotide GCGGCCCGGG (GC-box) followed by the alternating stretch
      (A)5(T)4(A)3(T)2(A)1(T)n (AT-box) led to the fixed polarity of the suffix
      insertions in the same micro-satellite sequences.

PMID- 8743014
TI  - [Directed transpositions in the genome of the mobile hobo element in a long-term
      selected strain of Drosophila melanogaster].
AB  - The object of our investigation was an inbred LA strain of Drosophila
      melanogaster. This strain was selected during more than 700 generations for low
      male mating activity and was characterized by complex abnormalities and the
      remarkably high level of spontaneous mutability. The last property is determined
      by hobo system of hybrid dysgenesis. LA strain's hobo activity potential in H-E
      system of hybrid dysgenesis comprise 30-40%. It may be drastically increased up
      to 70-80% through LA-strain chromosome isogenization in dysgenic crosses. In
      genomes of independent isogenic LA substrains, numerous directional
      transpositions of hobo element take place. In spite of it, the retention of hobo
      element insertion sites inherent in original LA persist. The obtained data open
      up a new possibilities to study the genome instability mechanisms.

PMID- 8743015
TI  - [The DNA polymorphism in the inhabitants of Ukraine detected with an M13 phage
      based probe].
AB  - BspRI and HinfI polymorphism of DNA in the inhabitants of Ukraine was analyzed
      with probe based on M13 phage. In the region 3 - 8 kb, the mean probabilities of
      coincidence of to marker bands comprised 0.22 for BspRI polymorphism and 0.34 for
      HinfI polymorphism. The indexes of similarity by Lee between the parents
      comprised 0.44 for BspRI polymorphism and 0.45 for HinfI polymorphism. The
      characteristics obtained may be used for the correct description of DNA
      fingerprints in the inhabitants of Ukraine.

PMID- 8743016
TI  - [The ratio of hereditary and environmental factors in the origination of
      noninfectious human diseases].
AB  - Recent investigations in clinical genetics have shown, that manifestations of
      common nontransmissive diseases in humans are determined by the interactions of
      hereditary, internal and environmental factors in the same way as it was earlier
      demonstrated for hereditary diseases and studied on animals and plants for many
      quantitative and qualitative traits.

PMID- 8743017
TI  - [Heterologous protein expression in the baculovirus vector system: the nuclear
      polyhedrosis virus of Malacosoma neustria in Antheraea pernyi cells].
AB  - The results of the creation of new expressive system on Malacosoma neustria
      nuclear polyhedrosis virus and cell line originated from Antheraea pernyi tissues
      was demonstrated. The expression of bacterial beta-galactosidase-coding gene was
      analyzed in this system.

PMID- 8743018
TI  - [A genetic analysis of the structure of hybrid populations of the green frog Rana
      esculenta L. complex (Amphibia, Ranidae) in Volhynia].
AB  - Analysis of the genetic structure of two green frog Rana esculenta complex
      populations from Volyn' was performed for 7 diagnostical loci. Populations of R-
      and REL-type were detected in which the introgression of Ldh-B allelic gene locus
      from R. lessonae into genome of R. ridibunda, characteristic for hybrid
      populations of Dnieper basin, was absent. This may be associated with alterations
      in gene pools of parental species.

PMID- 8743019
TI  - [The effect of chronic ionizing radiation at low doses on a number of
      reproductive indices in CC57W/Mv mice from an experimental Chernobyl population].
AB  - The effects of low doses of environmental ionizing radiation on reproductive
      functions of seven generations of CC57W/Mv mice from Chernobyl experimental
      population has been investigated. A decrease in the number of litters per female
      during reproductive period, the number of newborn animals per litter, and an
      increase in the postnatal mortality during the first month of life were shown.
      These effects are due to the stable disorders of parental reproductive system and
      the high level of in-vivo preimplantation deaths in F1--F7 generations of
      CC57W/Mv mice from the Chernobyl experimental populations.

PMID- 8743020
TI  - Environmentally-regulated genes of hypertension.
AB  - Several monogenetic causes of hypertension have recently been identified, but for
      the most part, the disease is of polygenic and possibly heterogenous character.
      The environmental impact, representing about 2/3 of blood pressure variance, is
      usually thought to be exerted at the level of phenotypic modification, additive
      to the effect of genetic loci determining blood pressure. The concept presented
      here is that for a significant part, the environment interacts with genes,
      influencing their expression. Of particular interest are stress genes expressed
      differentially in human and experimental hypertension. They may constitute
      candidate genes of blood pressure and heart weight, influenced by environmental
      stressors at the level of gene expression.

PMID- 8743021
TI  - Immediate early genes in blood pressure regulation.
AB  - The immediate early genes c-fos and c-jun are transcription regulating factors. c
      fos expression is widely used as a marker of neuronal activation and has been
      used in this study to identify those neurons, presumably vasomotor neurons, that
      are activated after interventions that alter blood pressure. c-fos and c-jun are
      expressed in the rostral ventral medulla (RVM) when the tonically active
      inhibitory inputs to the RVM are removed, either acutely or chronically, as in
      the SHR model of gentic hypertension. The injection of antisense oligonucleotide
      complementary to c-fos mRNA in the RVM attenuates the expression of c-fos, lowers
      resting blood pressure and attenuates blood pressure responses that are evoked
      via RVM mechanisms. These studies suggest a link between immediate early gene
      expression in neurons in the RVM and the regulation of blood pressure. c-fos
      could have an important role in regulating the activity of these central
      cardiovascular neurons. The role of the immediate early gene c-jun in
      cardiovascular control remains to be elucidated.

PMID- 8743022
TI  - New central mediators as targets of centrally acting antihypertensive drugs.
AB  - The modulation of peripheral sympathetic activity by the central nervous system
      may involve various pathways, neurotransmitters and receptors. In particular
      central catecholaminergic neurones and alpha-adrenoceptors have been analysed in
      detail, and they are recognized as important targets of the classic centrally
      acting antihypertensives clonidine, guanfacine and alpha-methyl-DOPA. Initially
      these drugs have been assumed to reduce elevated blood pressure via the
      stimulation of central alpha 2-adrenoceptors in the brain stem, thus leading to
      peripheral sympathoinhibition and a reduction of elevated blood pressure, heart
      rate and plasma catecholamines. In a later stage it has been recognized that
      central imidazoline (I1) receptors, probably located in the nucleus reticularis
      lateralis in the medullary region may also be involved in the central regulation
      of peripheral sympathetic activity, and for that matter as a target of centrally
      acting antihypertensives. Moxonidine and rilmenidine are the prototypes of such
      agents. Accordingly, the receptor profile of the various types of centrally
      acting antihypertensives may be characterized as follows: [formula: see text] The
      various compounds mentioned will thus cause peripheral sympathoinhibition,
      initiated by different receptor targets in the CNS. Finally, the peripheral alpha
      1-blocker urapidil has been demonstrated to possess an additional central
      mechanism, mediated by the stimulation of serotonergic 5HT1A-receptors located in
      the rostral ventrolateral medulla.

PMID- 8743023
TI  - The evidence for a pathophysiologic significance of the sympathetic overactivity
      in hypertension.
AB  - Interest for the role of the sympathetics in the genesis of hypertension has come
      full circle from early enthusiasm, through a period of neglect, to present
      understanding that strong evidence cannot be ignored. Sympathetic overactivity
      starts in childhood and is easily evident in 30% of patients with incipient
      hypertension. Later, in advanced hypertension, altered cardiovascular
      responsiveness obscures the obvious signs of sympathetic overactivity but the
      brain maintains its decisive pathophysiologic role. The early onset, the bimodal
      distribution of the neurogenic "hyperkinetic" pattern and familial aggregation
      suggest a genetic component in sympathetic overactivity. Patients with
      hypertension are at high risk for coronary disease and some of that risk is not
      directly related to blood pressure elevation. High sympathetic tone explains the
      pathophysiology of "pressure-independent" risk for premature coronary
      atherosclerosis in hypertension and for excess mortality/morbidity in patients
      who had already developed coronary heart disease.

PMID- 8743024
TI  - Pathogenetic factors in hypertension. Endothelial factors.
AB  - In normotensive humans, endothelium modulates vascular tone mainly by the
      production of nitric oxide. In human essential hypertension the basal release of
      nitric oxide is reduced and forearm vasodilation to the endothelium-dependent
      agonists acetylcholine or bradykinin is blunted. Defective basal release of
      nitric oxide seems to be secondary to blood pressure increase while impaired
      agonist-evoked endothelium-dependent vasodilation is probably a primary
      phenomenum. This latter endothelial dysfunction seems to be caused by the
      simultaneous presence of an alteration in the L-arginine-nitric oxide pathway and
      the production of constrictor prostanoids. Defective nitric oxide production is
      already detectable in normotensive offspring of hypertensive patients and young
      essential hypertensive. In contrast, vasoconstrictor prostanoid production seems
      to be associated with aging. In essential hypertensive patients, although only
      scanty data are available, chronic effective pharmacological treatment seems to
      restore impaired basal production of nitric oxide but does not improve vascular
      response to endothelial agonists.

PMID- 8743025
TI  - Insulin sensitivity in the pathogenesis of hypertension and hypertensive
      complications.
AB  - Epidemiologic and clinical studies suggest an association between
      hyperinsulinemia (and insulin resistance) and hypertension. This relationship is
      not present in secondary forms of hypertension and may persist despite adequate
      antihypertensive therapy. Normotensive offspring of hypertensive parents are
      also, as a group, insulin resistant and hyperinsulinemic. The association of
      hyperinsulinemia (and insulin resistance) with hypertension is more marked in the
      obese but present in lean hypertensive as well. Physiological mechanisms by which
      insulin might increase blood pressure include sympathetic nervous system
      stimulation and enhancement or renal sodium reabsorption. Evidence exists linking
      both of these mechanisms to hypertension. Insulin is also independently
      associated with myocardial infarction and microalbuminuria, two long term
      complications of high blood pressure. Experimentally induced decreases in insulin
      resistance and hyperinsulinemia, furthermore, have been associated with decreased
      blood pressure. In summary, the evidence suggests that hyperinsulinemia (and
      insulin resistance) exerts a pro-hypertensive effect that may be important in the
      pathogenesis of hypertension and hypertensive complications in some patients with
      essential hypertension.

PMID- 8743026
TI  - Evaluation of arterial compliance in humans.
AB  - Compliance is a measure of the elastic properties of arterial vessels and is a
      function of blood pressure. In recent years new techniques have been developed
      which allow to measure arterial compliance non invasively and continuously over
      the range of existing blood pressure values. It has been thus possible to
      investigate the alterations of arterial compliance in a variety of diseases and
      to address the physiological factors involved in arterial compliance modulation.
      This article will focus on the new data available on these issues.

PMID- 8743027
TI  - Hypertension, coronary artery and cerebrovascular diseases in the population. Has
      epidemiology changed in the last decades?
AB  - Life expectancy has significantly increased in the last decades in many western
      populations, due to the fall of total and cardiovascular death rate. However,
      morbidity from cardiovascular diseases has decreased to a smaller extent. The
      overall population risk profile has improved, but it is still unsatisfactory.
      This is true for blood pressure control (with only 20% of hypertensive patients
      achieving normotension with antihypertensive drugs), hypercholesterolemia (with
      borderline-high serum cholesterol levels in 50% of the population), and smoking
      habits. Other potential causes of the poor cardiovascular prevention are: 1) a
      limited knowledge of the optimal blood pressure goal with antihypertensive
      treatment, 2) scanty information on the long term effects of antihypertensive
      drugs on cerebral and coronary circulation. Finally, little is being done to
      improve primary prevention in youth, when the slowly progressing atherosclerotic
      plaque formation is already on the way. To improve the cost / effectiveness of
      cardiovascular prevention, efforts must concentrate on the early identification
      of the subjects at the highest risk and on health promotion among youngsters.
      Large epidemiological trials conducted from the early 50s have provided
      convincing evidence of the multifactorial origin of cardiovascular diseases and
      encouraged the implementation of population based primary and secondary
      preventive measures, including antihypertensive treatment, as well as dietary and
      life-style modifications. It is now time to start asking ourselves whether or not
      we are satisfied with the results obtained in terms of reduced morbidity and
      mortality, whether these results are the direct consequence of these measures and
      whether or not we can do even better. The present work reviews some of the most
      recent comparative reports on the epidemiology of cardiovascular diseases in
      different populations, and some intervention trials to answer these questions and
      to help in identifying the most cost-effective approach to cardiovascular disease
      prevention in the next few years.

PMID- 8743028
TI  - The new WHO Expert Committee Report on Hypertension Control.
AB  - A new WHO Expert Committee Report on Hypertension Control has recently been
      prepared. This paper is not intended to be a detailed summary of this report. It
      rather intends to identify the principal issues where the new report differs from
      the previous 1978 WHO report, to point out the aspects where it has substantially
      incorporated the recommendations made on the 1993 WHO/ISH guidelines, and to
      mention the issues that have been developed in this report more extensively than
      in previous WHO or WHO/ISH documents.

PMID- 8743029
TI  - Control of hypertension in the population. Strategies in affluent and developing
      countries.
AB  - Control of hypertension in population. Strategies in affluent and developing
      countries. The control of hypertension encompasses primary prevention, early
      detection and adequate treatment of high blood pressure. Primary prevention
      involves action at the population level to reduce obesity, alcohol and salt
      consumption, and to increase physical activity. The management of hypertension
      involves diagnostic work-up, assessment of overall cardiovascular disease risk,
      non-pharmacological and pharmacological treatment. The majority of community
      control programmes emphasized detection and treatment, rather than primary
      prevention. There are limitations to pharmacological treatment of hypertension,
      as shown by various studies, where a significant proportion of hypertensives have
      not been controlled by the treatment applied. In addition, the blood pressure
      cardiovascular risk relationship is continuous and progressive and, even within
      the conventionally defined "normotensive" range, complications occur with escape
      control. Developing countries will encounter the problem of prohibitive costs of
      care and drug treatment for hypertension. Therefore greater emphasis must be put
      on primary prevention in population control of hypertension.

PMID- 8743030
TI  - Cost-effectiveness of hypertension treatment.
AB  - The benefits of antihypertensive treatment are influenced by both the absolute
      initial cardiovascular risk, and the relative reduction. Because age is a major
      determinant of the absolute cardiovascular risk, and because the strategies for
      hypertension diagnosis and treatment are not very much influenced by age,
      hypertension management appears to be more cost-effective after the age of 45, in
      both men and women. Below this age, the absolute gain in life-years seems to be
      smaller, and sensitivity analysis demonstrate an important influence on the
      results of assumptions about the effects of treatment on quality of life and the
      discounting rate.

PMID- 8743031
TI  - Impact of guidelines for antihypertensive treatment on clinical practice.
AB  - Many Guidelines and Consensus Statements were published in 1993 and 1994. The
      pressure to produce these guidelines comes from clinicians faced with rapid
      change, from a wish to provide an independent authoritative view rather than rely
      on commercial promotion of particular treatments, and from governments seeking
      assistance with the allocation of scarce resources. Evaluation of the impact that
      guidelines exert on clinical practice is notoriously difficult, but has been
      attempted using the self-report questionnaire, or the more reliable but expensive
      analysis of actual practice data, before and after publication of the guidelines.
      Rigorous evaluation has been attempted and reported in North America and in
      Europe, in relation to surgical and obstetrical procedures and psychiatric
      disorders as well as medical treatments. Specific evaluation of the impact of
      recommendations from the Joint National Committee in the USA, for the treatment
      of hypertension, has also been attempted, as well as surveys of doctors'
      perceptions of Consensus Statements. The evidence available suggests that the
      main value obtained from Guidelines and Consensus Statements lies in their
      capacity to codify good or "best practice", at times of rapid change in a
      particular field. They also serve as a source of support for local opinion
      leaders, and as they are usually produced by respected authors they have
      substantial influence with Government. Guidelines are not effective in producing
      rapid change in clinical practice. If a change in practice is sought a more
      comprehensive program of action is necessary, with guidelines as one useful
      element.

PMID- 8743032
TI  - The case for a greater blood pressure fall.
AB  - Several large intervention trials in hypertension have shown that treated
      hypertensive patients are at increased risk of cardiovascular morbidity and
      mortality in spite of being treated. One possible explanation for this is the
      fact that the treated blood pressure rarely if ever is brought down to strictly
      normotensive levels. Against this view is the J-curve argument that suggests that
      too vigorous lowering of blood pressure may increase cardiovascular risks. Two
      prospective intervention trials have addressed this problem, the BBB Study, which
      has been published, and the much larger HOT Study which is still ongoing. Some of
      the findings in these two trials will be discussed with an emphasis on giving an
      up-date of the HOT Study.

PMID- 8743033
TI  - Antihypertensive treatment in the elderly.
AB  - Drug treatment with beta-blockers and diuretics in hypertensive men and women
      aged 70 and above confers highly significant and clinically relevant reductions
      in cardiovascular (especially stroke) morbidity and mortality. This satisfactory
      effect is not impaired by a low tolerability of the drugs used. Furthermore,
      treatment of elderly hypertensives with beta-receptor blockers and/or diuretics
      is cost-effective. In STOP-Hypertension the cost-effectiveness ratios were low
      and of the same magnitude for both men and women. The clinical implication of
      this is that blood pressure lowering therapy should be considered in elderly
      hypertensives, at least up until they are 80 years old. It should also be
      remembered that elderly patients often have other diseases than hypertension and
      that the drug treatment should be adjusted accordingly, e.g. by using a calcium
      antagonist or an ACE inhibitor, when indicated.

PMID- 8743034
TI  - Ambulatory blood pressure, blood pressure variability and antihypertensive
      treatment.
AB  - Ambulatory blood pressure monitoring is frequently employed in the clinical
      practice to improve the diagnosis of hypertension and the appropriateness of the
      decision regarding initiation of antihypertensive treatment. It is also
      frequently employed to check the efficacy of this treatment in conditions
      resembling daily life. This paper will describe the effect of a number of
      antihypertensive drugs on ambulatory blood pressure, based on data collected by
      our group in the past 10 years. It will then discuss the advantages of ambulatory
      blood pressure in studies of efficacy of antihypertensive drugs and the
      importance of this approach for definition of the trough-to-peak ratio of the
      antihypertensive effect. Some technical and clinical problems inherent to the
      ambulatory blood pressure monitoring approach will also be discussed.

PMID- 8743035
TI  - Compliance with antihypertensive treatment.
AB  - Compliance to antihypertensive treatment is a critical factor conditioning the
      success of therapy. It has been calculated that, depending on the method used to
      monitor compliance, only 20 to 80% of treated hypertensives can be considered as
      good compliers. In the past years it was thought that compliance was only a
      patient's problem but instead, the role of the physician in determining patient's
      compliance is very important. He should give clear information about the risks of
      the disease, the advantages of therapy and how to take medicines. He should also
      prescribe a therapeutic scheme as simple as possible avoiding multiple drug
      administrations and informing patients about possible side-effects. Subjects at
      particular risk of poor compliance (middle aged males, still active in work,
      without previous cardiovascular diseases) must be particularly monitored. In any
      case of poor response to therapy it is important to suspect poor compliance. A
      standardization of the methods for recording compliance is needed especially in
      clinical trials. The results of experimental studies in fact can be misleading if
      compliance is not taken into account.

PMID- 8743036
TI  - Key issues regarding lifestyle in the prevention and treatment of hypertension.
AB  - Lifestyle is a major determinant of hypertension and its complications in
      populations. This paper highlights some of the key issues relating to the gap
      between theory and practice in prevention and management of hypertensive
      cardiovascular disease. The need for new approaches and further research is
      emphasized.

PMID- 8743037
TI  - Antiatherosclerotic effects of antihypertensive drugs: recent evidence and
      ongoing trials.
AB  - The issue as to whether antihypertensive drugs may exert some antiatherosclerotic
      effect, at least partly independent of blood pressure lowering, has been explored
      in several experimental models of atherosclerosis, and a large body of evidence
      has been obtained in favor of a specific antiatherosclerotic action of calcium
      antagonists and ACE-inhibitors. On the clinical side, several studies are
      investigating the problem in hypertensive patients in whom progression of carotid
      intima-media thickness (IMT) and atherosclerotic plaques is explored by sensitive
      quantitative B-mode ultrasound techniques. The MIDAS has indicated a slower
      progression, at least in the first six months, of carotid plaques in isradipine
      treated patients than in diuretic-treated ones. However, MIDAS as a pioneer study
      has been particularly valuable in giving information on the rate of growth of IMT
      in hypertensive patients and on the best end-point to use in carotid ultrasound
      trials. Baseline data of the ongoing studies ELSA and VHAS have so far provided
      evidence of the very high prevalence of carotid atherosclerosis among
      hypertensive patients, an observation that makes the evaluation of the
      antiatherosclerotic action of some antihypertensive agents even more important.
      Finally, the PHYLLIS trial using a factorial design, beside exploring the
      antiatherosclerotic action of an ACE-inhibitor vs a diuretic, intends to evaluate
      the possible benefits of associating antihypertensive therapy with lipid lowering
      by a statin on the progression of carotid atherosclerosis.

PMID- 8743038
TI  - Can the kidney prevent cardiovascular diseases?
AB  - The kidneys play an important role in the development of cardiovascular risk
      factors. It is well known that heavy proteinuria can induce hyperlipidemia, the
      uric acid is elevated in some renal deficiencies and that hypertension develops
      in most end stage renal diseases. In prehypertensive states, specially in
      subjects with a family history of hypertension, some hemodynamic changes take
      place, characterized by an increase in renal vasoconstriction with a reduction in
      renal plasma flow and an elevation of sodium reabsorption. The mechanisms for
      these alterations are not well understood, but an increase in intracytosolic
      calcium in vascular smooth muscle cells, a reduction in vasodilatory substances
      such as nitric oxide and an increased sympathetic nervous activity have been
      proposed. In normotensive subjects with two hypertensive parents a reduction in
      sodium diet, an increase in protein intake or in arginine diet could prevent
      established essential hypertension from developing. In borderline hypertension an
      early therapy with low doses of calcium antagonists, ACE inhibition or diuretics
      could be indicated.

PMID- 8743039
TI  - Cardiovascular structural alterations in hypertension: effect of treatment.
AB  - Available data support the hypothesis that antihypertensive drugs may determine a
      significant regression of cardiac and vascular structural changes.
      Antihypertensive drugs that inhibit the renin-angiotensin or, to a lesser extent,
      the adrenergic system may more consistently and promptly reduce left ventricular
      hypertrophy (LVH) and vascular structural changes. It is possible that all
      antihypertensive agents, when used for long enough periods, will reduce LV mass,
      whereas only certain drugs will reduce mass within a period of few months, so
      that any difference among classes of antihypertensive drugs is more quantitative
      than absolute. However, a rapid reversal of LVH may be particularly important
      because reducing blood pressure in the presence of an elevated LV mass may be
      associated with impairment of coronary perfusion. Structural changes of small
      resistance arteries play a significant role in the genesis of increased vascular
      resistance in hypertension and in the maintainance of high blood pressure values.
      Studies in humans have demonstrated that minimal vascular resistance can be
      reduced with the use of different antihypertensive drugs, while a complete
      normalization of the media: lumen ratio was observed only with ACE inhibitors.
      Further studies are needed to assess the true clinical impact, in terms of
      reduced morbidity and mortality of reversal of cardiovascular structural changes
      in hypertensive patients. However, available studies indicate that reversal of
      LVH reduces the pathological consequences of increased left ventricular mass, and
      preliminary data suggest that complete regression of LVH may be associated to a
      decreased risk for cardiovascular events.

PMID- 8743040
TI  - Diuretics and risk of sudden death in hypertension--evidence and potential
      implications.
AB  - Randomized trials have produced solid evidence that non potassium-sparing
      diuretic therapy in hypertension is beneficial, but the controversy regarding the
      possibility that these drugs may increase the risk of sudden death in some
      patients continues. Although few sudden deaths were reported in the trials,
      findings indicate that an excess risk of sudden death in users of these diuretics
      exists (pooled risk ratio 1.5; 95% CI 1.1-2.0). Two recent case-control studies
      provide consistent evidence that non potassium-sparing diuretics are associated
      with a twofold risk of sudden death compared to potassium-sparing diuretic
      therapy. It is estimated that among the 400,000 men and 1,000,000 women treated
      for hypertension in the Netherlands, such as excess risk would lead to
      respectively 96 and 34 cases of sudden death. We conclude that the available
      evidence strongly suggests that hypertensive patients on non potassium-sparing
      diuretic therapy are at an increased risk of sudden death. Concomitant
      prescription of potassium-sparing diuretic agents should be considered in these
      patients.

PMID- 8743041
TI  - Primary and secondary prevention of stroke.
AB  - Data from prospective observational studies indicate that usual levels of blood
      pressure are directly and continuously related to the risk of stroke. a prolonged
      difference in usual diastolic blood pressure levels of just 5 mmHg would
      eventually confer about a one-third difference in stroke risk, with similar
      proportional effects in hypertensives and non-hypertensives. The results of
      randomised trials of blood pressure lowering drugs in hypertensive patients
      suggest that much or all of this long-term potential stroke avoidance can be
      achieved within just a few years of beginning treatment. Overall in 17 randomised
      trials of antihypertensive treatment, a net blood pressure reduction of 10-12
      mmHg systolic and 5-6 mmHg diastolic, conferred a reduction in stroke incidence
      of 38% SD 4, with similar reductions in fatal and non-fatal stroke. Additionally,
      the sizes of the reductions were similar in trials in mild, moderate or more
      severe hypertension, in trials in older or younger patients and in trials in
      patients with or without a history of cerebrovascular disease. Because the
      proportional effects of treatment were similar in all these groups, the absolute
      effects of treatment on stroke varied in direct proportion to the background risk
      of stroke. The greatest benefits were, therefore, observed among those with a
      history of cerebrovascular disease, those above the age of 60 years, and those
      with more severe hypertension.

PMID- 8743042
TI  - Primary and secondary prevention of myocardial infarction.
AB  - The prevention of coronary artery disease (CHD) and particularly of myocardial
      infarction (MI) is based on some well designed strategies aimed at treating both
      asymptomatic high-risk patients (primary prevention) and patients with
      established CHD (secondary prevention). A positive impact from primary prevention
      can be basically achieved trough a reduction in high blood pressure and by
      correcting dyslipidemia. The benefit can be substantially increased by smoking
      cessation, increasing physical exercise, reduction of body weight, use of post
      menopausal oestrogen, moderate alcohol consumption and use of high doses of
      vitamin E in those patients who are compliant with the specific strategies.
      Secondary prevention of MI can be again obtained by controlling blood pressure
      and reducing serum cholesterol in patients surviving acute MI who can also
      benefit from the administration of beta-blockers, aspirin and probably ace
      inhibitors particularly in presence of left ventricular dysfunction. We suggest
      that in both arms of prevention, significant results can be achieved mainly by a
      multifactorial approach capable of correcting all the modifiable risk factors
      that contribute to the rather complex pathogenesis of CHD.

PMID- 8743043
TI  - Left ventricular dysfunction and heart failure. Mechanistic and therapeutic
      distinctions.
AB  - Dysfunction of the left ventricle may result from a variety of insults, all of
      which may initiate a self-perpetuating process of ventricular remodeling which
      may progress to end-stage heart disease. Symptoms of heart failure may or may not
      co-exist with this ventricular remodeling. Treatment and prevention of these two
      largely distinct entities differ. Symptoms may respond to diuretics, vasodilators
      and digoxin. Progressive ventricular remodeling may be slowed by angiotensin
      converting enzyme inhibitors, hydralazine + isosorbide dinitrate and beta
      blockers. Prevention of symptomatic heart failure is dependent on early
      recognition of ventricular dysfunction and aggressive treatment to slow its
      progression. Development of more effective and targeted therapies will be
      dependent on expanded insight into the cellular and molecular mechanisms
      contributing to the remodeling process.

PMID- 8743044
TI  - Experimental approaches to determining the choice of first-step therapy for
      patients with hypertension. The ALLHAT Research Group Antihypertensive and Lipid
      Lowering Treatment to Prevent Heart Attack Trial.
AB  - Detection, treatment and control of hypertension is one of the best proven
      approaches to prevention of cardiovascular disease. Antihypertensive treatment
      trials have convincingly demonstrated that diuretics and beta-blockers reduce the
      risk of stroke and coronary heart disease. Corresponding information is not yet
      available for newer classes of antihypertensive drug therapy such as calcium
      channel blockers, angiotensin converting enzyme inhibitors and alpha 1 receptor
      blockers. Several experimental studies are now addressing this question. The
      largest such trial (n = 40,000) is the Antihypertensive and Lipid-Lowering
      Treatment to Prevent Heart Attack Trial (ALLHAT). This manuscript describes two
      studies (TOMHS and the VA study on antihypertensive agents) that compared several
      classes of antihypertensive drugs with regard to blood pressure outcomes and
      ALLHAT, which is comparing the effect of four first-step approaches to
      antihypertensive therapy on combined incidence of fatal coronary heart disease
      and non-fatal myocardial infarction.

PMID- 8743045
TI  - Prevention of hypertension and associated cardiovascular disease. A 1995
      statement. Conclusions from a joint WHO/ISH Meeting.

PMID- 8743046
TI  - Effect of alpha-tocopherol and Trolox on the decomposition of methyl linoleate
      hydroperoxides.
AB  - To clarify the mechanisms of antioxidant action, the effect of alpha-tocopherol
      and its water-soluble carboxylic acid derivative, Trolox, was studied on the
      decomposition of methyl linoleate hydroperoxides (MeLoOOH). Decomposition rate
      and the distribution of autoxidation products formed from MeLoOOH were followed
      by analyzing the volatile and non-volatile products by static headspace gas
      chromatography and normal-phase high-performance liquid chromatography,
      respectively. Both alpha-tocopherol and Trolox markedly inhibited the
      decomposition of MeLoOOH in a concentration-dependent way. In the absence of
      antioxidants, MeLoOOH was completely decomposed after incubation for 48 h at 60
      degrees C, and in the presence of equal molar concentration of antioxidants only
      6-7% of initial MeLoOOH was decomposed even after 280 h of incubation. MeLoOOH
      produced 1.2% methyl linoleate hydroxy compounds (MeLoOOH) in the presence of
      alpha-tocopherol and 3.8% in the presence of Trolox. Both antioxidants inhibited
      the formation of volatile decomposition products and the formation of ketodiene
      compounds. The hydroxy compounds may be formed by the reaction of alkoxy radical
      and hydrogen donating antioxidants. Conversion of MeLoOOH into stable MeLoOH
      demonstrated that the antioxidants alpha-tocopherol and Trolox trap alkoxyl
      radicals by H-donation.

PMID- 8743047
TI  - Physiochemical characterization of ATP binding to human 5-lipoxygenase.
AB  - Human 5-lipoxygenase requires ATP as a stimulatory factor. At the two preferred
      concentrations of the free Ca2+, 0.02 microM with a resting cell and 20 microM
      with a stimulated cell, Scatchard analysis revealed that 5-lipoxygenase has one
      affinity ATP binding site with a Kd of 4.6 microM at the low Ca2+ concentration
      but has two affinity ATP binding sites with a higher Kd of 4.4 microM and a lower
      Kd of 14.5 microM at the high Ca2+ concentration. In contrast, in a Tween 20
      reaction system, 5-lipoxygenase had similar activation coefficients for ATP at
      both Ca2+ concentrations; these were 12.7 microM at the low Ca2+ concentration
      and 12.0 microM at the high Ca2+ concentration. These results showed that 5
      lipoxygenase has an ATP binding site and suggest that self-association of 5
      lipoxygenase in 20 microM Ca2+ may affect ATP binding affinity as measured by
      Scatchard analysis.

PMID- 8743048
TI  - Sterol specificity of the Saccharomyces cerevisiae ERG6 gene product expressed in
      Escherichia coli.
AB  - The ERG6 gene from Saccharomyces cerevisiae has been functionally expressed in
      Escherichia coli, for the first time, yielding a protein that catalyzes the
      bisubstrate transfer reaction whereby the reactive methyl group from (S)-adenosyl
      L-methionine is transferred stereoselectively to C-24 of the sterol side chain.
      The structural requirements of sterol in binding and catalysis were similar to
      the native protein from S. cerevisiae. Inhibition of biomethylation was observed
      with fecosterol and ergosterol which suggests that ergosterol may function in
      wild-type yeast as feedback regulator of sterol biosynthesis.

PMID- 8743049
TI  - Purification and characterization of a Penicillium sp. lipase which discriminates
      against diglycerides.
AB  - A lipase was isolated from Penicillium sp. strain UZLM-4 and characterized. This
      lipase has a molecular weight of 27,344 (determined by mass spectrometry) and
      hydrolyzes triglycerides in preference to mono- and diglyceride substrates. Among
      various triglyceride substrates, tributyrin is hydrolyzed about four times faster
      than any other tested. The lipase has a preference for hydrolysis at the 1,3
      positions of the lipids and shows a weak stereoselectivity for the S enantiomer.
      Unlike most other lipases, this lipase is stable and has a high activity at low
      surface pressures (5-10 mN/m).

PMID- 8743050
TI  - Sphingomyelin metabolism is linked to salt transport in the gills of euryhaline
      fish.
AB  - By in vivo and in vitro studies of L-(3-3H)serine and [9,10(n)-3H]palmitic acid
      incorporation into phospholipids, we show a change in the renewal of the ceramide
      moiety of sphingomyelin in the gills of euryhaline fish (sea bass and eels) when
      the animals were subjected to abrupt alterations in environmental salinity. In
      vivo, decrease of the salinity from sea water (salinity 3.7%) to diluted sea
      water (salinity 1%) induced an increase of label incorporation into gill
      sphingomyelin. The same was true when gills from sea water-adapted sea bass or
      sea water-adapted eels were incubated in diluted sea water. A decrease in free
      ceramides synthesis was also observed in the gills of sea water-adapted sea bass
      when the salinity of the incubation medium was reduced. Direct inhibition of
      Na+/K(+)-ATPase activity with ouabain decreased the sphingomyelin synthesis in
      the gills of sea bass during in vitro incubation in diluted sea water, whereas
      treatment with furosemide stimulated sphingomyelin synthesis in the same gills
      incubated in sea water. These findings indicate that changes in Na+ fluxes modify
      the sphingomyelin turnover and control the production of free ceramides and
      sphingosine in gill cells of euryhaline fish. In view of the well-known effects
      of these sphingomyelin degradation products on isolated tumor cell
      differentiation, we suggest that they play a very important role in modulating
      chloride cell distribution and metabolism of fish gills during abrupt changes in
      environmental salinity.

PMID- 8743051
TI  - Studies on phospholipid biosynthesis in hepatocytes from alcoholic rats by using
      radiolabeled exogenous precursors.
AB  - We have studied the synthesis of phospholipids in hepatocytes isolated from
      chronically ethanol-treated rats by using isotopically labelled serine,
      ethanolamine, and choline as exogenous precursors. Our results demonstrate that
      ethanol induces specific effects on the biosynthesis of phosphatidylethanolamine
      and phosphatidylcholine via CDP-derivatives and also on the synthesis of
      phosphatidylserine via the Ca(++)-dependent base-exchange reaction. Thus, the
      synthesis of phosphatidylethanolamine from [3-H]ethanolamine and the
      incorporation of [3H]serine into phosphatidylserine were clearly higher in
      hepatocytes from ethanol-treated rats compared to controls. The synthesis of
      phosphatidylcholine from [methyl-14C]choline, on the other hand, decreased
      markedly, suggesting a specific inhibition of cholinephosphotransferase activity.
      We have also demonstrated that the phosphatidylcholine levels are markedly
      decreased in hepatocytes isolated from chronically ethanol-treated rats as a
      consequence of the lower phosphatidylcholine biosynthesis. The decrease in the
      incorporation of radioactivity from choline to betaine, which we also found, is
      interpreted as being the result of a higher use of betaine as methyl donor
      instead of methionine to maintain the hepatic S-adenosylmethionine levels in
      chronic alcoholism.

PMID- 8743052
TI  - Dietary eritadenine-induced alteration of molecular species composition of
      phospholipids in rats.
AB  - The effect of dietary eritadenine, a hypocholesterolemic compound found in the
      mushroom Lentinus edodes, on the fatty acid and molecular species profiles of
      phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in the plasma and
      liver microsomes was investigated in relation to the hypocholesterolemic action
      of the compound in rats. Animals were fed the control or eritadenine-supplemented
      (50 mg/kg diet) diet for 14 d. Eritadenine supplementation significantly
      decreased the plasma concentrations of cholesterol and phospholipids, but not
      triglycerides. The PC/PE ratio of liver microsomes, but not plasma, was also
      markedly decreased by eritadenine. Eritadenine supplementation was found to
      increase the proportion of 18:2n-6 and, inversely, to decrease the proportion of
      20:4n-6 and 22:5n-6 in plasma PC and liver microsomal PC and PE, indicating that
      eritadenine depressed the metabolism of linoleic acid. The effect of eritadenine
      on the profile of n-3 fatty acids was dissimilar in PC and PE. These changes in
      fatty acid composition were selectively reflected in the molecular species
      composition of both PC and PE; the extent of increase in 16:0-18:2 molecular
      species or decrease in 18:0-20:4 molecular species was apparently greater than
      that of other molecular species containing 18:2 or 20:4 in the sn-2 position.
      These results suggest that, in addition to the decrease in liver microsomal PC/PE
      ratio, the alteration of plasma PC molecular species composition might also
      participate in the hypocholesterolemic action of eritadenine.

PMID- 8743053
TI  - Intestinal lymph absorption of butter, corn oil, cod liver oil, menhaden oil, and
      eicosapentaenoic and docosahexaenoic acid ethyl esters in rats.
AB  - Adult male rats were surgically given a drainage catheter in the main mesenteric
      lymph duct. After an overnight fast, five groups of rats received
      intragastrically, in one bolus, butter, corn oil (CO), cod liver oil (CLO),
      menhaden oil (MO), or ethyl esters of eicosapentaenoic (EPA) and docosahexaenoic
      (DHA) acids (K80). Intestinal lymph was collected in these conscious animals,
      each hour during the first 6 h and in a single sample for the next 18 h. The
      absorption peak appeared earlier after MO and CO than after CLO administration.
      The quantities of triglycerides recovered during the first 6 h were significantly
      lower after butter (91 mg) and K80 (54 mg) administration than for the other
      three oils. No difference was observed between the vegetable oil and the marine
      oils (CO = 173 mg, CLO = 148 mg, MO = 180 mg). The total triglyceride recovered
      in 24 h was highest after CLO (410 mg) and lowest with K80 (146 mg). An increase
      in the weight percentage of some characteristic fatty acids of the lipid mixtures
      was observed: oleic acid for butter, oleic and linoleic acids for CO, EPA and DHA
      for CLO, MO, and K80. Chylomicrons were the largest with CO, more numerous and
      smaller with CLO, and the smallest with K80. Results obtained illustrated the
      relation between gastrointestinal hydrolysis, enterocyte biochemical events, and
      lymph triglyceride absorption profiles as related to the composition and
      distribution of triglyceride fatty acids.

PMID- 8743055
TI  - A rapid method for separation of plasma low and high density lipoproteins for
      tocopherol and carotenoid analyses.
AB  - Ultracentrifugation (UC) is the method most often employed for separation and
      quantification of lipoproteins. Because this procedure requires expensive
      laboratory equipment, a large volume of fresh sample and an inordinate amount of
      time, it may not be ideal for routine clinical/experimental use. The aim of the
      current study was to evaluate a method which combines selective precipitation
      (HDL-P) and immunoseparation (LDL-I) for the rapid and reliable isolation of high
      density lipoproteins (HDL) and low density lipoproteins (LDL) specifically for
      vitamin E and carotenoid determination within these fractions. Cholesterol and
      triacylgylcerol concentrations within the HDL and LDL were also determined to
      enable expression of vitamin E and carotenoid concentrations per gram of lipid.
      Isolation of lipoproteins by UC was used as the reference method (HDL-UC/LDL-UC).
      There were no significant differences between methods for alpha- and gamma
      tocopherol in LDL and HDL. Carotenoids measured in HDL and LDL were comparable
      between the methods. The exception was higher lutein/zeaxanthin concentration in
      HDL-P and LDL-I compared to HDL-UC and LDL-UC, respectively. Additionally,
      lycopene concentration was significantly lower in LDL-I compared to LDL-UC. In
      comparing vitamin E and carotenoid values in lipoproteins separated from fresh
      and frozen plasma by the direct method, there was no difference in alpha
      tocopherol or the majority of carotenoids measured. In conclusion, a combination
      of selective precipitation and immunoseparation of fresh or frozen plasma for
      subsequent alpha- and gamma-tocopherol analyses provides an accurate and reliable
      alternative to lipoprotein separation by UC. Additionally, carotenoid
      concentrations in HDL separated by selective precipitation and analyses of alpha-
      and beta-carotenes and beta-cryptoxanthin in LDL separated by immunoseparation
      are also reliable, while lycopene and lutein/zeaxanthin concentrations in LDL-I
      are not readily comparable to LDL-UC.

PMID- 8743054
TI  - Comparative hypocholesterolemic effects of six vegetable oils in cholesterol-fed
      rat.
AB  - The hypocholesterolemic efficacies of various polyunsaturated fatty acids were
      compared in rats given cholesterol-enriched diets. Oenothera biennis Linn oil
      (OBLO, linoleic + gamma-linolenic), sunflower oil (linoleic), palm oil (PLO,
      oleic + linoleic), soybean oil (linoleic + alpha-linolenic), high-oleic safflower
      oil (oleic + linoleic), or mixed oil (linoleic + alpha-linolenic) was added to
      the diet at 200 g/kg (20% groups). OBLO was also added at 100 g/kg diet (10%
      group). The serum total and very low density lipoprotein + intermediate
      lipoprotein + low density lipoprotein cholesterol concentrations of the 10 and
      20% OBLO groups were consistently lower than those in the other groups. The liver
      cholesterol concentration in the PLO group was lower in all groups. The liver
      cholesterol concentrations in the 10 and 20% OBLO groups were also lower than in
      the other groups. There were no significant differences in the fecal neutral
      sterol and bile acid extraction among groups.

PMID- 8743056
TI  - Estimation of polyunsaturated fatty acid content in lipids of aquatic organisms
      using thin-layer chromatography on a plain silica gel plate.
AB  - We have designed a rapid method for the separation of polyunsaturated fatty acids
      (PUFA, > or = trienes) from non-PUFA, and for estimation of total amounts of PUFA
      in lipids of aquatic organisms. Lipids from thirty-one species, including marine
      and fresh water fishes, shell fishes, marine algae, and other aquatic animals,
      and from terrestrial organisms, were transesterified with sodium methoxide in
      methanol. The resulting fatty acid methyl esters were separated by thin-layer
      chromatography on commercially available plain silica gel plates with a
      developing solvent of n-hexane/ethyl ether/acetic acid (95:5:1, by vol). All of
      the methyl esters from aquatic organisms tested separated into two spots, whereas
      those from terrestrial sources, except for linseed oil, showed a single
      unresolved spot. The upper and lower spots were scraped separately from the
      plate, and their fatty acid compositions were determined by gas-liquid
      chromatography. The lower spot was composed of PUFA having more than two double
      bonds, whereas components of the upper spot were saturated, monoenoic, and the
      greater part of the dienoic fatty acids. When the spots on the silica gel plate
      were stained with Coomassie brilliant blue, the amounts of PUFA in aquatic
      organisms could be estimated satisfactorily using a scanning densitometer.

PMID- 8743057
TI  - Increased hepatic synthesis and accumulation of plasma apolipoprotein B100 in
      copper-deficient rats does not result from modification in apolipoprotein B mRNA
      editing.
AB  - Experimentally induced copper deficiency in the rat results in increased plasma
      apolipoprotein B100 (apo B100) concentration in association with increased
      hepatic apo B100 synthesis. This enhancement of apo B100 synthesis and plasma
      accumulation accounts for the rise of plasma low density lipoprotein in these
      animals. In the present study, we have investigated if the selective increase in
      hepatic apo B100 synthesis is accounted for by changes in apo B mRNA editing.
      Reverse transcription coupled with polymerase chain reaction amplification and
      primer extension analysis of apo B cDNA revealed no differences in apo B mRNA
      editing in either the liver or small intestine between control and copper
      deficient rats. We speculate that the increase in apo B100 synthesis in the liver
      of copper-deficient rats reflects posttranslational alterations in gene
      expression accompanying changes in very low density lipoprotein assembly and
      secretion.

PMID- 8743058
TI  - Postnatal changes in activation of polyunsaturated fatty acid, acylation of
      lysophosphoglyceride, and phosphorylation of diacylglycerol in cortical gray
      matter of rat cerebrum.
AB  - Activation of polyunsaturated fatty acid, acylation of lysophosphoglyceride, and
      phosphorylation of diacylglycerol in postnatal developing rat cerebrum were
      studied in vitro, using cortical gray matter homogenates. The rate of n-3 and n-6
      fatty acid activation was maximal at ten days after birth and minimal at
      adulthood. Acylation of lysophosphoglyceride was most active at the neonatal
      stage and gradually decreased with age. In addition, the amount of phosphatidic
      acid formed from 1, 2-dioleoyl-glycerol was also maximum at the neonatal stage,
      and then gradually decreased. These results suggest that the specific activity of
      glycerolipid synthesis in cortical gray matter declines during postnatal
      development.

PMID- 8743059
TI  - Neutral sterols of sawflies (Symphyta): their relationship to other Hymenoptera.
AB  - To investigate sterol utilization in sawflies, the neutral sterols of four
      species of sawflies were determined by gas-liquid chromatography and mass
      spectrometry, and compared to the respective dietary plant material. Cholesterol
      was the predominant (55-76%) sterol in all species and stages of sawflies
      examined. Host plants, however, contained primarily sitosterol (50-88%), along
      with other 24-alkylsterols and only 0.5-5.9% cholesterol, indicating that the
      sawflies examined are capable of dealkylating the C28 and C29 phytosterols in
      their diet to cholesterol. Comparative sterol metabolism in Hymenoptera is
      discussed.

PMID- 8743060
TI  - Identification of a novel all-cis-5,9,12-heptadecatrienoic acid in the cellular
      slime mold Polysphondylium pallidum.
AB  - The all-cis-5,9,12-heptadecatrienoic acid was identified in the cellular slime
      mold Polysphondylium pallidum. The structural elucidation was accomplished by
      capillary gas chromatography, argentation thin-layer chromatography, and gas
      chromatography/mass spectrometry. This fatty acid has not been reported
      previously.

PMID- 8743061
TI  - Improving health care, Part 1: The clinical value compass.
AB  - CLINICAL VALUE COMPASS APPROACH: The clinical Value Compass, named to reflect its
      similarity in layout to a directional compass, has at its four cardinal points
      (1) functional status, risk status, and well-being; (2) costs; (3) satisfaction
      with health care and perceived benefit; and (4) clinical outcomes. To manage and
      improve the value of health care services, providers will need to measure the
      value of care for similar patient populations, analyze the internal delivery
      processes, run tests of changed delivery processes, and determine if these
      changes lead to better outcomes and lower costs. GETTING STARTED--OUTCOMES AND
      AIM: In the case example, the team's aim is "to find ways to continually improve
      the quality and value of care for AMI (acute myocardial infection) patients."
      VALUE MEASURES--SELECT A SET OF OUTCOME AND COST MEASURES: Four to 12 outcome and
      cost measures are sufficient to get started. In the case example, the team chose
      1 or more measures for each quadrant of the value compass. OPERATIONAL DEFINITION
      OF MEASURES: An operational definition is a clearly specified method explaining
      how to measure a variable. Measures in the case example were based on information
      from the medical record, administrative and financial records, and patient
      reports and ratings at eight weeks postdischarge. COMMENTS: Measurement systems
      that quantify the quality of processes and results of care are often add-ons to
      routine care delivery. However, the process of measurement should be intertwined
      with the process of care delivery so that front-line providers are involved in
      both managing the patient and measuring the process and related outcomes and
      costs.

PMID- 8743062
TI  - Morning report: a forum for reporting adverse drug reactions.
AB  - BACKGROUND: Most hospitals that monitor adverse drug reactions (ADRs) through
      reporting by nurses, pharmacists, medical record technicians, and quality
      improvement staff experience low rates of reporting. In teaching hospitals,
      inadequate orientation about the hospital activities, frequent changes in
      rotations between hospitals, and time commitments to educational pursuits may all
      undermine house staff's ability to perform ADR monitoring. The authors describe
      their experience since 1989 at the Department of Veterans Affairs Medical Center
      in Amarillo, Texas, in the use of verbal ADR reporting by physicians (mostly
      house staff) during the morning report in the medical service. ADR MONITORING
      PROGRAM: The morning report begins with a discussion of adverse outcomes of
      medications, usually from the previous 24 hours. The staff physicians use the
      opportunity to address the nature of the ADRs and the clinical circumstances
      leading up to them. Some ADR episodes require further peer review by a physician
      before being forwarded to the Pharmacy and Therapeutics Committee. EFFECT OF THE
      PROGRAM: Since the start of the ADR monitoring program in 1989, the number of
      self-reported ADRs in the medical service has increased over historical controls,
      even though no special training was given to house staff to detect ADRs. The
      surgical and psychiatric services, which did not hold morning reports, did not
      experience the same increase in ADR reports. CONCLUSIONS: The ADR monitoring
      program is notable for the simplicity of the reporting mechanism, the integration
      of the reporting into the regular work flow activities, the concurrent nature of
      the reporting, the educational opportunities, and the potential benefit for
      quality improvement of patient care.

PMID- 8743063
TI  - Phase II of the AHCPR-sponsored heart failure guideline: translating practice
      recommendations into review criteria.
AB  - BACKGROUND: In 1992, under the sponsorship of the U.S. Agency for Health Care
      Policy and Research, RAND assembled an expert panel to develop the Heart Failure
      Clinical Practice Guideline. Phase II of the effort was intended to identify
      which of the guideline's recommendations the panel felt were suitable for use in
      retrospective utilization review and quality assessment programs and to develop
      review criteria, performance measures, and standards of quality for use in
      monitoring compliance with those recommendations. SELECTION OF RECOMMENDATIONS:
      Selecting guideline recommendations for translation into review criteria and
      ultimately into standards of care was a multistep process comprising (1)
      identification of 34 recommendations from the guideline, (2) rating them on the
      basis of importance to quality of care and feasibility of monitoring, (3) review
      by a subcommittee and the full guideline panel, (4) translation into review
      criteria, and (5) further review and input by panelists and peer and pilot
      reviewers. Finally, standards of care (the minimum proportion of cases expected
      to be in accordance with guideline recommendations) were determined to be 90%-95%
      for six of the final criteria and 75%-80% for the other two. CONCLUSION: Despite
      some reservations, physicians and other health care professionals agreed to be
      held accountable for following a core set of guideline recommendations for the
      treatment of heart failure. Substantial progress was made in identifying
      recommendations that panelists and reviewers were willing to endorse in
      utilization review activities, including adoption of improved documentation
      standards. The review criteria's major impact may be the knowledge that the
      criteria are in place and that care is being monitored based on those standards.

PMID- 8743064
TI  - Evidence-based medical education: the missing variable in the quality improvement
      equation.

PMID- 8743065
TI  - Developing and implementing health care guidelines for group medical practices:
      an interview with Gordon Mosser. Interview by Stephen L. Davidow.

PMID- 8743066
TI  - Epidemiology, clinical spectrum and prognostic value of mixed cryoglobulinaemia
      in hepatitis C virus patients: a prospective study.
AB  - A prospective study was undertaken to evaluate the prevalence, incidence,
      clinical spectrum and prognostic value of mixed cryoglobulinaemia in HCV
      infection. Four-hundred and thirty-two consecutive patients with chronic liver
      disease, 303 HCV-related, 81 HBV-related, 14 nonB-nonC related, and 34 of non
      viral aetiology were studied. Cryoglobulinaemia was detected in 139 (46%) of the
      HCV-related chronic hepatitis patients, in 4 (5%) of the HBV-related and in none
      of the chronic hepatitis patients of any other aetiology. Cryoglobulinaemia was
      associated with liver cirrhosis, the duration of liver disease and predominantly
      with the female sex. HCV and anti-HCV antibodies were present in all the
      cryoprecipitates. All the HCV genotypes were associated with cryoglobulinaemia.
      In a high percentage of patients, the amount of cryoglobulinaemic was low and
      about half of the cryoglobulinaemic patients showed a clinical syndrome. The
      incidence per year of cryoglobulinaemia (6%) and of related signs was low. A
      higher incidence of malignant lymphoproliferative diseases was observed in type
      II cryoglobulinaemia. The presence of a cryoglobulinaemia-related clinical
      syndrome plays a role in the prognosis of patients with chronic hepatitis C.

PMID- 8743067
TI  - Ornidazole in the treatment of active Crohn's disease: short-term results.
AB  - The object of this work was to test the efficacy of ornidazole in patients with
      active Crohn's disease. Twenty-five patients with active Crohn's disease (Crohn's
      disease activity index greater than 150 points) participated in this open study.
      The analysis of results was based on changes in the severity of the Crohn's
      disease activity index measured at entry and at the end of the first, second, and
      third and fourth week. Analysis of variance, correlation analysis, multiple
      regression analyses and chi-square test were used for statistical evaluation of
      results. The results showed that the Crohn's disease activity index fell
      gradually from week 0 to week 4 (p < 0.001), while the number of patients going
      into remission increased gradually from week 0 to week 4 (18/25 patients, 75%).
      Sex, location of disease, age at onset, first attack or recurrence and duration
      of disease were not statistically related to response to treatment. Presence and
      severity of abdominal pain both decreased and bowel movements were also reduced.
      General well-being improved significantly, the loss of weight stopped and an
      increase in body weight was noted at the end of the fourth week. Side effects
      were minimal. It is concluded that ornidazole is an effective and safe drug for
      the treatment of active Crohn's disease.

PMID- 8743068
TI  - Long-term variations of serum laminin and procollagen III peptide in chronic HCV
      hepatitis after alpha-interferon therapy.
AB  - Twenty-three out of 40 patients affected by chronic HCV hepatitis responded (i.e.
      aminotransferases returned to normal) after 6-month treatment with 6 MU tiw of
      recombinant alpha-interferon 2a (IFN); in 11 (Group 1), the remission was
      maintained for a mean observation time of 33.15 months (range 20-50) after
      withdrawal of therapy; 12 (Group 2) relapsing after IFN withdrawal, were treated
      again obtaining in 10 a second response. Seventeen did not respond (Group 3).
      Serum markers of connective tissue metabolism (laminin and aminoterminal peptide
      of type III procollagen -NPIIIP-) were assayed in all patients before treatment
      and every 6th month, to evaluate long-term effects of IFN therapy. In non
      responders, NPIIIP after treatment was not different from baseline, while laminin
      significantly increased at 6 and 12 months; in responders, NPIIIP decreased
      significantly after therapy, maintaining values lower than baseline on long-term
      observation. Laminin decreased significantly six months after the end of therapy
      and remained lower than baseline in all sustained responders. In this group, the
      drop in laminin was progressive, whereas in Group 2, laminin showed only a slight
      decrease on long-term control. Our data show that these serum markers
      persistently decrease in sustained responders to IFN, while in relapsed cases,
      prolonged therapy is needed to obtain minor effects on laminin; on the contrary,
      in non-responders, NPIIIP remains unchanged and laminin significantly increases,
      suggesting a persistence of active fibrogenesis.

PMID- 8743069
TI  - In vitro study comparing the ability of mono-octanoin and mono-octanoin plus
      methyl tert-butyl ether to dissolve biliary stones.
AB  - This in vitro study compared the gallstone dissolution rates of mono-octanoin,
      mono-octanoin plus 10% distilled water, and mono-octanoin plus methyl tert-butyl
      ether 2:1. Sixteen stones were treated with each solvent at a slow perfusion rate
      of 3-4 ml/h and a rapid perfusion rate of 2.5 ml/30 min with 20-sec
      instillation/aspiration cycles, both with and without bile. The stones were
      weighed before, and 3, 6, 12 and 24 hrs after the start of treatment: the solvent
      was changed every 30 min. After 24 hrs of instillation/aspiration without bile,
      the mono-octanoin/methyl tert-butyl ether mixture reduced the weight of the
      stones by 93%, mono-octanoin plus water by 63%, and mono-octanoin alone by 52%;
      with bile, the figures were, respectively, 86%, 42% and 40%. The mono
      octanoin/methyl tert-butyl ether mixture thus took approximately half the time
      needed by the other two preparations to dissolve the stones to the same extent, a
      finding which may be relevant for the clinical dissolution of bile duct stones.

PMID- 8743070
TI  - Unusual thoracic collaterals of gastro-oesophageal varices in a patient with end
      stage liver disease.
AB  - Thoracic varices are rare anomalies in patients with liver cirrhosis and portal
      hypertension. Gastro-oesophageal varices usually drain into the azygos or
      hemiazygos vein. The case is reported here of an unusual collateral pathway of
      gastro-oesophageal varices with drainage to the vena anonyma system presenting as
      lung masses on chest X-ray, which completely resolved after successful liver
      transplantation.

PMID- 8743071
TI  - Epithelioid haemangioendothelioma of the liver: report of a case submitted to
      orthotopic liver transplantation.
AB  - A case of hepatic epithelioid haemangio-endothelioma is described in a 42-year
      old female who presented with abdominal pain and hepatomegaly. The radiographic
      finding showed multiple hepatic lesions in both lobes. Diagnosis was based on the
      liver biopsy. The tumour cells were immunoreactive with factor VIII related
      antigen and vimentine. A liver transplantation was performed. Although at the
      time of diagnosis there was no clinical evidence of metastasis, the intra
      operatorive examination revealed multiple mesenteric and pulmonary neoplastic
      nodules. The patient is alive and well seven months after liver transplantation.

PMID- 8743072
TI  - Hepatic abscess caused by Salmonella typhi: diagnosis and management by
      percutaneous echo-guided needle aspiration.
AB  - Three cases of liver abscesses due to Salmonella typhi (2 solitary, 1 with double
      localization in the right lobe) are described in which specific diagnosis was
      based on percutaneous echo-guided aspiration of the lesions. Haemocultures and
      coprocultures were negative, in all cases, and pus-cultures of aspirated material
      from cavities grew Salmonella typhi; Widal became significantly positive only in
      one patient 15 days after discharge. Percutaneous needle drainage, combined with
      chloramphenicol therapy, was successfully performed under echo guidance; only in
      one case was a second aspiration needed three days after the first one. Fever
      disappeared within 48-72 hours after drainage of the abscess. No complications or
      side-effects were observed.

PMID- 8743073
TI  - Extracorporeal shock wave lithotripsy (ESWL) of gallbladder stones: experience in
      Bolzano.
AB  - During a period of 24 months, 115 patients with symptomatic gallbladder stones
      (77 females, 38 males; median age 46 years, range 22-87) were treated by
      extracorporeal shock wave lithotripsy with a Lithostar Plus. Concomitant bile
      acid dissolution therapy (ursodeoxycholic acid + chenodeoxycholic acid 7.5
      mg/kg/day each or tauroursodesoxycholic acid 5-10mg/kg/day) was administered
      until 3 months after total fragment clearance. Complete clearance of all
      fragments was obtained after 6, 9, 12, 18 and 24 months in, respectively, 30, 45,
      51, 62 and 72%. Life table analysis of the subgroups showed significantly better
      clearance results in patients with fragments < 5mm at the first extracorporeal
      shock wave lithotripsy session (67%) than in patients with larger fragments (39%)
      (p < 0.01). Patients with solitary stones < 20mm cleared their fragments better
      (58%) at 12 months than those with multiple stones (49%), but the differences
      were not statistically significant. Stone recurrence was 6% at 1 year and was
      lower in patients with solitary stones (3%) than in those with multiple stones
      (12%). Major side effects consisted in 2 cases of mild acute pancreatits and 19%
      of biliary colics.

PMID- 8743074
TI  - Ultrasonic evaluation of gallbladder emptying with ceruletide.
AB  - In order to develop a practical and reproducible method to assess gallbladder
      function, gallbladder emptying was studied by ultrasound in 27 gallstone patients
      after i.m. administration of ceruletide (0.3 micrograms/kg), and the procedure
      was compared to oral cholecystography with fatty meal. Maximal percent
      gallbladder contraction was reached in all patients 30 min after ceruletide.
      Maximal percent contractions were 47.5 +/- 27.7 during ultrasound with ceruletide
      and 33.9 +/- 16.3 during oral cholecystography with fatty meal (p = 0.03). A
      significant linear relationship was found between the results obtained with the
      two different procedures (r = 0.57; p = 0.002). Serial ultrasound determinations
      of gallbladder emptying were performed in 16 patients. Day-to-day variation was
      below 20% in 11 subjects, and it ranged between 20 and 40% in 5 subjects. Minor
      side effects were observed in 9 patients. Ultrasound determination of gallbladder
      emptying after ceruletide appears to be a practical and reliable method to assess
      gallbladder function.

PMID- 8743075
TI  - Gastric pathology by Helicobacter pylori: recent advances in physiopathology
      diagnosis and therapy. Naples, Italy, October 20, 1995.

PMID- 8743076
TI  - Box-Jenkins modelling in medical research.
AB  - Notifications of diseases, entries in a hospital, injuries due to accidents,
      etc., are frequently collected in fixed equally spaced intervals. Such
      observations are likely to be dependent. In environmental medicine, where series
      such as daily concentrations of pollutants are collected and analysed, it is
      evident that dependence of consecutive measurements may be important. A high
      concentration of a pollutant today has a certain 'inertia', i.e. a tendency to be
      high tomorrow as well. Dependence of consecutive observations may be equally
      important when data such as blood glucose are recorded within a single patient.
      ARIMA models (autoregressive integrated moving average models, Box-Jenkins
      models), which allow the stochastic dependence of consecutive data to be
      modelled, have become well established in such fields as economics. This article
      reviews basic concepts of Box-Jenkins modelling. The methods are illustrated by
      applications. In particular, the following topics are presented: the ARIMA model,
      transfer function models (assessment of relations between time series) and
      intervention analysis (assessment of changes of time series).

PMID- 8743077
TI  - Structural time series models in medicine.
AB  - Structural time series models are formulated in terms of components, such as
      trends, seasonals and cycles, which have a direct interpretation. This article
      describes such models and gives examples of how they can be applied in medicine.
      Univariate models are considered first, and then extended to include explanatory
      variables and interventions. Multivariate models are then shown to provide a
      framework for modelling longitudinal data and for carrying out intervention
      analysis with control groups. The final sections deal with data irregularities
      and non-Gaussian observations.

PMID- 8743078
TI  - Spectral analysis of clinical signals: an interface between medical statisticians
      and medical engineers.
AB  - This paper reviews the current use of spectral analysis in clinical medicine. We
      cover the problems of aliasing and estimation of the spectrum using windowing and
      autoregressive techniques. These techniques are modified for nonstationary data
      to include evolutionary spectral analysis and recursive autoregressive methods.
      The relationship between evolutionary spectral analysis and the time-frequency
      methods such as the Wigner-Ville distribution is discussed. Other techniques
      covered are Walsh Transforms and cosinor analysis. The methods are shown to apply
      in the analysis of signals from heart rate, blood pressure, EEG, other electrical
      signals and hormone levels. The engineering and statistical approaches are
      contrasted.

PMID- 8743079
TI  - The analysis of the EEG.
AB  - The quantitative analysis of the electroencephalogram (EEG) relies heavily on
      methods of time series analysis. A quantitative approach seems indispensable for
      research (be it clinical or basic neurophysical research), but it can also be a
      useful information for purely clinical purposes. Apart from the ongoing
      spontaneous EEG, evoked potentials (EPs) also play an important role. They can be
      elicited by simple sensory stimuli or more complex stimuli. Their analysis
      requires methods which are different from those for the spontaneous EEG. Those
      methods operate usually in the time domain and offer many challenging problems to
      statisticians. Methods for analysing the spontaneous EEG usually work in the
      frequency domain in terms of spectra and coherences. Biomedical engineers who
      take care of the equipment are usually also trained in time series analysis.
      Thus, they have contributed much more to methodological progress for analysing
      EEGs and EPs, compared with statisticians. However, the availability of a sample
      of subjects, and the associated problems in modelling followed by an inferential
      analysis could make a larger influence from the statistical side quite
      profitable. This paper tries to give an overview of a fascinating area. In doing
      so we treat more extensively problems with some statistical appeal. This leads
      inevitably to some overlap with our own work.

PMID- 8743080
TI  - High quantifiable levels of p24 antigenemia are detectable in HIV type 1-infected
      patients.

PMID- 8743081
TI  - ADA, a potential anti-HIV drug.

PMID- 8743082
TI  - Doxorubicin inhibits Tat-dependent transactivation of HIV type 1 LTR.
AB  - Tat, the human immunodeficiency virus (HIV)-encoded transcription factor, is
      vital for HIV replication and transcription. Any drug that inhibits Tat's
      activity is a valuable candidate for chemotherapeutic applications. We show here
      that doxorubicin (Dox), a well-known anticancer drug and its derivative,
      daunomycin, inhibit the ability of Tat to activate the HIV-1 LTR. We
      contransfected HeLa cells with pSV40TAT and a chloramphenicol acetyltransferase
      gene driven by an HIV LTR promoter. CAT transcription was vigorously stimulated
      many fold by Tat production but the effect of Tat was inhibited by Dox in a dose
      dependent manner. The transcriptional activation domain of Tat, located in its 67
      amino terminal residues, remains Dox sensitive. A TAR-deleted reporter gene with
      a Gal binding domain is transactivated by a Gal-Tat fusion protein. This
      transcription complex retains a high level of activity in the presence of Dox,
      suggesting that Dox primarily affects RNA-Tat, rather than DNA-Tat, mediated
      transactivation. RNA gel mobility analysis reveals that Dox does not affect the
      binding of Tat to TAR-RNA in vitro but does increase the binding activity of
      cellular nuclear proteins with TAR-RNA. Induction or activation of such TAR
      binding proteins in cells that might interfere with the activity of Tat could
      explain the observed inhibitory effects of Dox on Tat-activated transcription.
      These results suggest that Dox may have chemotherapeutic effects on HIV
      expression mediated through TAR RNA.

PMID- 8743083
TI  - Gamma delta-T cell-receptor-positive lymphocytes inhibit human hematopoietic
      progenitor cell growth in HIV type 1-infected patients.
AB  - In severe HIV infection, the majority of patients exhibit signs of hematopoietic
      deficiency including anemia, leukopenia, and thrombocytopenia. Besides other
      pathophysiological mechanisms, the disturbed helper/suppressor ratio of T
      lymphocytes suggests that alterations within T cell subpopulations may have a
      suppressive effect on HIV-associated hematopoiesis. Since a delta TCS-1- and
      mostly CD-8-positive subpopulation of cytotoxic T-lymphocytes expressing the
      gamma delta-receptor is increased in peripheral blood and bone marrow of HIV
      infected persons, it was the aim of this study to investigate the role of gamma
      delta-positive cells in HIV-associated bone marrow deficiency. The number of bone
      marrow-derived pluripotent colony-forming units (CFU-GEMM), burstforming units
      erythrocyte (BFU-E), and colony-forming units-granulocyte-monocyte (CFU-GM) of
      HIV-1-positive patients was significantly (p < 0.05) increased after depletion of
      CD-8-positive, gamma delta-positive, and delta TCS-1-positive T-lymphocytes. In
      contrast, the depletion of these subpopulations had no stimulatory effect in
      healthy controls. Further experiments identified direct cellular contact between
      effector and hematopoietic progenitor cells and the production of interferon
      gamma and tumor necrosis factor-alpha as the mechanisms mediating the suppressive
      effect of the delta TCS-1-positive cells in HIV-positive patients.

PMID- 8743084
TI  - Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of
      persons with stable nonprogressing HIV type 1 infection.
AB  - Some individuals in well-defined cohorts have now been infected with HIV-1 for
      well over a decade and yet remain clinically asymptomatic with normal CD4 counts.
      To determine immunologic and virologic parameters in these individuals, we
      examined 10 persons from the San Francisco City Clinic with firmly documented
      infection of 11-15 years duration who had maintained stable CD4 counts above 500
      cells/microliters. Our results indicate that long-term nonprogressors are a
      heterogeneous group with respect to viral load and HIV-1-specific immune
      responses, and that progression can occur even after 15 years of stable
      infection. However, in a subset of persons with the lowest viral loads and
      persistent nonprogressive infection, we detected strong CTL responses, whereas
      neutralizing antibody studies revealed weak to undetectable titers against a
      panel of 10 primary isolates. This study demonstrates that a vigorous in vivo
      activated HIV-1-specific CTL response can be part of the host immune response in
      stable nonprogressive HIV-1 infection, and that circulating activated CTL can be
      detected in the setting of an extremely low viral load. These results also
      indicate that long-term nonprogressing HIV-1 infection does not require the
      presence of broadly cross-reactive neutralizing antibodies.

PMID- 8743085
TI  - Prediction of HIV peptide epitopes by a novel algorithm.
AB  - Identification of promiscuous or multideterminant T cell epitopes is essential
      for HIV vaccine development, however, current methods for T cell epitope
      identification are both cost intensive and labor intensive. We have developed a
      computer-driven algorithm, named EpiMer, which searches protein amino acid
      sequences for putative MHC class I- and/or class II-restricted T cell epitopes.
      This algorithm identifies peptides that contain multiple MHC-binding motifs from
      protein sequences. To evaluate the predictive power of EpiMer, the amino acid
      sequences of the HIV-1 proteins nef, gp160, gag p55, and tat were searched for
      regions of MHC-binding motif clustering. We assessed the algorithm's predictive
      power by comparing the EpiMer-predicted peptide epitopes to T cell epitopes that
      have been published in the literature. The EpiMer method of T cell epitope
      identification was compared to the standard method of synthesizing short,
      overlapping peptides and testing them for immunogenicity (overlapping peptide
      method), and to an alternate algorithm that has been used to identify putative T
      cell epitopes from primary structure (AMPHI). For the four HIV-1 proteins
      analyzed, the in vitro testing of EpiMer peptides for immunogenicity would have
      required the synthesis of fewer total peptides than either AMPHI or the
      overlapping peptide method. The EpiMer algorithm proved to be more efficient and
      more sensitive per amino acid than both the overlapping peptide method and AMPHI.
      The EpiMer predictions for these four HIV proteins are described. Since EpiMer
      predicted peptides have the potential to bind to multiple MHC alleles, they are
      strong candidates for inclusion in a synthetic HIV vaccine.

PMID- 8743086
TI  - A monoclonal antibody defines a novel HIV type 1 Tat domain involved in trans
      cellular trans-activation.
AB  - In the present study, a CAT assay, a beta-galactosidase assay, and
      immunofluorescence analysis have been used to study the cellular uptake of the
      HIV-1 Tat protein. An anti-Tat MAb binding to an epitope comprising both the
      basic domain and the RGD sequence inhibits trans-activation by exogenous Tat. Two
      different full-length recombinant Tat proteins were used in these studies. The
      inhibitory MAb, however, recognized only one of the recombinant Tat proteins.
      Immunofluorescence analysis demonstrated that only the Tat protein recognized by
      the inhibitory anti-Tat MAb was taken up by COS and HeLa cells. This indicates
      that there are conformational differences between the two Tat proteins and that a
      correct folding of the epitope recognized by the anti-Tat MAb is required for
      cellular uptake. The recombinant Tat taken up by the cells was distributed
      between the nucleoli, the nucleoplasm, and along the nuclear membrane.
      Interactions between Tat and serum components were shown in vitro and also
      inhibition of trans-cellular trans-activation by fetal calf serum in tissue
      culture was demonstrated. The specific inhibition of the cellular uptake of Tat
      by an anti-Tat monoclonal antibody and the blocking of uptake by serum components
      implies specific binding of Tat to the cell membrane.

PMID- 8743087
TI  - Interferon gamma stimulates cell-mediated transmission of HIV type 1 from
      abortively infected endothelial cells.
AB  - Human umbilical vein endothelial cells (HUVEC) can be abortively infected with
      HIV-1, but virus production is rescued by T cells. The influence of interferon
      gamma (IFN-gamma) in this experimental system has been investigated. HUVEC either
      untreated or treated with IFN-gamma were infected with HIV-1 and cocultivated
      with rescuer T cells. Virus yield was subsequently assessed as antigen or
      infectivity present in the cocultures supernatants. Viral DNA in HUVEC was
      detected by polymerase chain reaction. Transmission electron microscopy was used
      to establish direct interactions between HUVEC and T cells. Intercellular
      adhesion molecule (ICAM)-1 expression by HUVEC was measured by enzyme-linked
      immunoassay. Monoclonal antibodies (MAbs) to adhesion molecules were used to
      block the rescue of infection by T cells. Treatment of HUVEC with IFN-gamma
      caused a dose-dependent enhancement of HIV-1 yield in cocultures of HUVEC with
      either lymphoblastoid or normal T cells. IFN-gamma was effective also when
      administered to HUVEC 1 day after infection. Neither HIV-1 adsorption nor virus
      reverse transcription was stimulated by IFN. Physical contact between HIV-1
      infected HUVEC and rescuer T cells was observed, and discrete tracts of
      discontinuity between the juxtaposed membranes were detected, being more frequent
      when HUVEC had been treated with IFN-gamma. Treatment with IFN determined an
      increase of ICAM-1 expression by HUVEC, and anti ICAM-1 MAbs inhibited HIV-1
      rescue, being more effective when HUVEC had been exposed to IFN-gamma. Treatment
      of T cells with anti-LFA-1 Mab also inhibited HIV-1 rescue. The enhancing effect
      of IFN-gamma could be the result of stimulated transfer of HIV-1 infection from
      HUVEC to T cells, possibly mediated by enhanced expression of ICAM-1 by HUVEC,
      that could, in turn, enhance the efficiency of membrane interaction with T cells.
      Since in HIV-1-infected patients circulating IFN-gamma is enhanced, our results
      can have pathogenetic implications.

PMID- 8743088
TI  - HIV type 1 Thai subtype E is predominant in South Vietnam.

PMID- 8743089
TI  - Endemicity and phylogeny of the human T cell lymphotropic virus type II subtype A
      from the Kayapo Indians of Brazil: evidence for limited regional dissemination.
AB  - Long terminal repeat (LTR)-based restriction fragment length polymorphism (RFLP)
      analysis of human T cell lymphotropic virus type II (HTLV-II) from 17
      seropositive Kayapo Indians from Brazil showed that all 17 samples contained a
      unique HTLV-IIa subtype (A-II). Additional RFLP screening demonstrated the
      presence of this subtype in two of three Brazilian blood donors and a Mexican
      prostitute and her child. In contrast, 129 samples from blood donors and
      intravenous drug users (IDUs) from the United States, two Pueblo Indian samples,
      five samples from Norwegian IDUs, and two samples from blood donors from Denmark
      were all found to be a different HTLV-IIa subtype (A-III). Phylogenetic analysis
      of two Kayapo and one Mexican LTR sequences showed that they cluster with a
      subtype A-II sequence from a Brazilian blood donor and with sequences from two
      prostitutes from Ghana and Cameroon. These results demonstrate that infection
      with the A-II subtype is endemic among the Kayapo Amerindians, has disseminated
      to non-Indian populations in Brazil, and is also present in Mexico. Furthermore,
      the A-II subtype does not appear to represent an origin for the HTLV-IIa
      infection in urban areas of the United States and Europe. This study provides
      evidence that HTLV-IIa may be a Paleo-Indian subtype as previously suggested for
      HTLV-IIb.

PMID- 8743090
TI  - HIV type 1 subtypes B and C from new regions of India and Indian and Ethiopian
      expatriates in Kuwait.

PMID- 8743091
TI  - Morphology and mechanics of muscle: two or one?

PMID- 8743092
TI  - Determination of muscle fibre orientation using Diffusion-Weighted MRI.
AB  - Biomechanical studies have shown that the distribution of stress and strain in
      biological tissue is strongly dependent on fibre orientation. Therefore, to
      analyze the local mechanical load, accurate data on muscle fibre orientation are
      needed. Traditional techniques to determine fibre orientation are inherently
      invasive. Here we used Diffusion Weighted MRI to non-invasively determine, in
      each image voxel of 0.23 x 0.23 mm, the diffusion tensor of water in the cat
      semimembranosus muscle. The direction corresponding to the largest eigenvector of
      this tensor was calculated. This direction was found to correspond qualitatively
      to the muscular fibre direction, as determined by visual inspection.

PMID- 8743093
TI  - Influence of the dynamical properties of the human masticatory muscles on jaw
      closing movements.
AB  - A dynamic six degrees-of-freedom mathematical model of the human masticatory
      system has been developed in order to study the contribution of the different
      masticatory muscles and their dynamical properties to the closing movement of the
      jaw. Muscles were included as forces acting according to their lines of action
      and the temporomandibular joints were modelled by linear elastic surfaces.
      Ligaments were not included. The geometry of the model was derived from a human
      cadaver. With this model symmetrical jaw closing movements were simulated. It was
      found that the normally observed jaw closing movement which includes a swing
      slide movement of the condyle along the articular eminence, can be generated by
      various separate pairs of masticatory muscles. Among the masticatory muscles the
      different parts of the masseter as well as the medial pterygoid muscle appeared
      to be the most suitable to complete this action. The dynamical muscle properties
      appeared to provide a mechanism causing the movements to pass off more smoothly.
      The force/length relationship of muscle fibres, which also introduced a limit for
      protrusive excursions of the lower jaw, turned out to play a predominant role in
      this mechanism.

PMID- 8743094
TI  - A 3-D finite element model of blood perfused rat gastrocnemius medialis muscle.
AB  - A finite element description of blood perfusion has been developed, and is
      applied to skeletal muscles. Three-dimensional distributions of blood pressures
      and flows in deforming muscles are calculated. The muscle tissue is considered as
      a fluid-saturated porous solid. The blood is modeled as a series of five
      intercommunicating compartmental fluids, representing arterial, arteriolar,
      capillary, venular and venous blood, that reside in the pores (blood vessels) of
      the muscle tissue. The blood vessels are modeled as distensible tubes, embedded
      in the muscle tissue. A 3-D finite element mesh has been mapped on a
      reconstructed geometry of a gastrocnemius medialis muscle of the rat. Blood
      perfused linear elastic muscle material behaviour has been assigned to this mesh.
      A simulation of blood perfusion, resulting from a constant arterio-venous
      pressure difference, through the reconstructed muscle has been performed.
      Calculated blood pressure and flow distributions were within physiological range.

PMID- 8743095
TI  - A two dimensional model for the prediction of muscle shape and intramuscular
      pressure.
AB  - Traditional pennate skeletal muscle models with straight fibres and straight
      tendinous sheets cannot assume realistic muscle shapes and are unsuitable for
      predicting intramuscular pressure. The two dimensional models proposed here have
      flexible fibres and tendinous sheets of which the curvatures are in mechanical
      equilibrium with the intramuscular pressure distribution. Analytical
      relationships between fibre stress, pressure, curvatures and lengths of fibres
      and tendinous sheets have been derived based on physical laws and functional
      demands. These relationships were used to generate unipennate muscle shapes and
      to calculate pressure distributions. The results compare well with the shapes of
      the medial gastrocnemius muscles of man and cat and with maximum intramuscular
      pressures as reported in the literature.

PMID- 8743096
TI  - Three-dimensional reconstruction of the rat triceps surae muscle and finite
      element mesh generation of the gastrocnemius medialis muscle.
AB  - In order to simulate blood flow in skeletal muscle, our group has developed a
      finite element description of perfused skeletal muscle. This model requires input
      parameters concerning the vascular system, muscle contraction and the geometry of
      a muscle, including its aponeuroses. The objective of the present paper is to
      create a geometrical reconstruction of the rat gastrocnemius medialis muscle that
      can be incorporated in the finite element model. Since this muscle is connected
      to the plantaris and the gastrocnemius lateralis muscle, a detailed computer
      graphical reconstruction of the triceps surae muscle, based on histological cross
      sections, has been accomplished first. Using this reconstruction, relevant
      sections were selected to create the finite element mesh of the gastrocnemius
      medialis muscle. Special attention was payed to the location of the aponeuroses.
      The mesh can be used in finite element simulations of perfused skeletal muscle.

PMID- 8743097
TI  - Optimization of left ventricular fibre orientation of the normal heart for
      homogeneous sarcomere length during ejection.
AB  - During the ejection phase of the cardiac cycle, left ventricular muscle fibres
      shorten while generating force. It was hypothesized that fibres are oriented in
      the wall such that the amount of shortening is the same for all fibres. We
      evaluated this hypothesis for the equatorial region of the left ventricle. In a
      finite element model of left ventricular wall mechanics fibre orientation was
      quantified by a helix angle which varied linearly from the inner to the outer
      wall. Fibre length was characterized by sarcomere length, set at 1.95 microns
      everywhere in the passive state of 0 transmural pressure. For a cavity pressure
      of 15 kPa, considered representative for ejection, inhomogeneity in mechanical
      loading was expressed by the variance of the sarcomere length. The variance was
      minimized by adapting the transmural course of fibre angle. First, only the slope
      was optimized and in a second optimization this was done for both slope and
      intercept. Optimal helix fibre angles were 69.6 degrees endocardially, 0 degree
      at the middle of the wall and -69.6 degrees epicardially for the first
      optimization and 78.2 degrees, 20.7 degrees and, -36.7 degrees respectively for
      the second. Sarcomere length changed from 1.95 to 1.975 +/- 0.012 and 1.981 +/-
      0.004 microns (mean +/- SD) respectively. CONCLUSION: After optimization
      calculated helix fibre angles were in the physiological range. Describing the
      transmural course of fibre angle with slope and intercept significantly improved
      homogeneity in mechanical load.

PMID- 8743098
TI  - Important experimental factors for skeletal muscle modelling: non-linear changes
      of muscle length force characteristics as a function of degree of activity.
AB  - In muscle modelling submaximal force exertion is often modelled on the basis of
      simple scaling of maximal length force characteristics. In such a case it is
      implicitly assumed that two basic physiological properties of muscle, i.e. length
      force characteristics and activity of the muscle by recruitment and firing rate
      coding are factors which independently determine actual muscle force. In this
      review it is argued that, on the basis of intracellular properties of muscle
      fibres as well as architectural variables of muscle morphology, muscle length
      force characteristics are affected in such a drastic way that the assumption of
      independence of these variables is no longer tenable.

PMID- 8743099
TI  - Intramyocardial pressure measurements in the isolated perfused papillary muscle
      of rat heart.
AB  - The intramyocardial pressure (IMP) plays a role in the interaction between heart
      contraction and coronary flow. In order to measure IMP we developed the isolated
      perfused papillary muscle. The papillary muscle was suspended in a muscle bath
      with oxygenated Tyrode's solution. Perfusion with Tyrode's solution took place
      via the septal artery. Diastolic intramyocardial pressure was measured with
      micropipettes with a tipdiameter of 3 to 4 microns in combination with the servo
      null technique. After an equilibration period of at least a half hour where the
      muscle was perfused with a perfusion pressure of 40 cmH2O and stimulated with 0.2
      Hz the IMP measurements started. Pressure changes resulting from changes in
      perfusion pressure and injection of ink via the pipette made it possible to
      distinguish between interstitial and vascular localization. No leakage along the
      shaft of the pipette to the outside was found. Perfusion caused interstitial
      edema in the muscle so that the cross-sectional area (CSA) of myocytes relative
      to total muscle CSA decreased from 71% in non-perfused muscle to 51% in perfused
      muscle. Interstitial edema increased approximately from 10% to 30%. The amount of
      edema was reduced by rapid pacing (3.3 Hz) as judged from decreased muscle
      diameter and a lower IMP. It is concluded that reliable IMP measurements can be
      made in the isolated papillary muscle and that increased filling of the
      interstitium increases its pressure.

PMID- 8743100
TI  - Decrease in high density lipoprotein cholesterol during prolonged storage. CELL
      Study Group.
AB  - Different studies on the stability of high density lipoprotein cholesterol (HDL)
      in frozen serum or plasma have yielded conflicting results, namely increase,
      decrease, or no change at all during prolonged storage under freezing conditions.
      As part of a major trial on lipid-lowering strategies we statistically
      demonstrated a time-related decrease in HDL cholesterol during storage up to 46
      months at -20 degrees C. We therefore re-analysed 85 frozen samples that had been
      analysed fresh and then stored from 26 to 46 months, using the dextran sulphate
      500/Mg2+ method. A linear regression analysis of change in HDL cholesterol on
      time was performed. The slope was significantly negative (p < 0.0005). The
      regression equation was (decrease in HDL) = 0.05 - 0.008 x (time in months), i.e.
      after 6 months' storage at -20 degrees C there was almost a 1% decrease in the
      HDL cholesterol concentration per month of storage.

PMID- 8743101
TI  - Reference limits for routine haematological measurements in 7-14-year-old
      children living at an intermediate altitude (1869 m, Erzurum, Turkey).
AB  - In order to obtain reference limits, complete blood counts were performed using
      an automated haematology analyser (Cell-Dyn 1500) on venous blood samples from
      718 healthy children living at 1869 m altitude. At first, to obtain appropriate
      populations for obtaining reference values, the factors of per capita income,
      parental educational status and antecedent infection(s) were assessed with
      respect to their effects on each parameter. Of the subgroups classified according
      to these factors, those which were affected in terms of haematological values
      were excluded. The effects of age and sex on the parameters were evaluated, and
      reference values were arranged according to age groups to facilitate clinical
      use. Among the reference values which we suggest for children living at about
      2000 m altitude, those of haemoglobin, haematocrit, red blood cell count and mean
      cell volume are significantly higher than sea-level values. In addition, our
      results indicate that intermediate altitude has no effect on other routine
      haematological values.

PMID- 8743102
TI  - Prevention of antigen-induced arthritis in rats by oral administration of the
      inducing antigen.
AB  - We investigated the effect of oral administration of methylated bovine serum
      albumin (mBSA) on antigen-induced arthritis (AIA) in rats that was induced by
      immunization with mBSA followed by the intra-articular injection of the same
      antigen. The results showed that the development of AIA was suppressed in a dose
      dependent manner by orally given mBSA. The suppression of AIA was associated with
      decreases in the delayed type hypersensitivity to mBSA and also in the
      proliferative response of inguinal lymph node cells to the antigen in mBSA-fed
      animals. These results indicate that oral administration of an antigen is an
      effective way to suppress arthritis induced by the antigen and that oral
      tolerance to the antigen appears to be critically involved in the suppression of
      arthritis.

PMID- 8743103
TI  - The MICRAL test for diabetic microalbuminuria: predictive values as a function of
      prevalence.
AB  - The MICRAL test is an immunospecific dipstick for detection of low concentrations
      of albumin in urine (microalbuminuria). The test is intended to be used for
      screening in an ambulatory setting. The utility of the test depends on its
      ability to accurately predict which patients will be classified as either
      microalbuminuric or normoalbuminuric by means of a standard laboratory method for
      determination of albumin in urine. We have analysed data from studies with a
      total of 2904 samples of urine from diabetic patients. The data are from our own
      study (190 samples) and from a selected set of 10 publications. The results from
      standard laboratory measurements of albumin in urine were used as " gold
      standards". The sensitivity and specificity as calculated from the pooled data
      were 83.2 and 92.3%, respectively. The predictive values were calculated using
      simulated changes in the prevalence of microalbuminuria (MAU). At a prevalence of
      MAU of 1% the predictive value of a negative test is 99.9% but that of a positive
      test only 9.8%. At a prevalence of MAU of 80% the positive predictive value is
      97.7% and the negative predictive value 57.9%. In general, any change in the
      prevalence will lead to a change in the predictive values. Thus the prevalence of
      MAU in the given clinical setting is a decisive factor in determining the utility
      of the MICRAL test.

PMID- 8743104
TI  - C-reactive protein: the difference between quantitation is serum and EDTA plasma.
AB  - We report the differences between using either EDTA plasma or serum in a
      turbidimetric assay for quantitation of C-reactive protein (CRP). A systematic
      discrepancy was found for these two sample materials. This was most pronounced in
      the low concentration range (below 20 mg1(-1)) at which lower values were found
      in serum than in EDTA plasma. Conversely, in the high concentration range, serum
      showed slightly higher values. Addition of K3-EDTA to the reaction buffer
      improved the kinetics for sera with low concentrations of CRP, thus increasing
      the sensitivity of the assay. We found an overall constant discrepancy of
      approximately 8% lower values in plasma than in serum (equally for low and high
      levels of CRP) after the addition of K3-EDTA. The most probable explanation for
      this effect seems to be the differing water content of serum and EDTA plasma. We
      discuss the role and function of EDTA in the CRP assay and suggest some
      hypothetical mechanisms.

PMID- 8743105
TI  - The effect of fructose metabolism on the accumulation of inositol phosphates in
      rat pancreatic islets.
AB  - The mechanism by which glucose recognition of B cells results in the release of
      inositol 1,4,5-trisphosphate is not known at present. In pancreatic islets,
      fructose shares a common metabolic pathway with glucose from the second step of
      glycolysis and can augment insulin secretion at stimulatory glucose levels. To
      evaluate the impact of glycolysis on the release of inositol 1,4,5-trisphosphate,
      we studied the effect of glucose and fructose metabolism on insulin secretion and
      the activation of inositol-specific phospholipase C, using collagenase digested
      rat pancreatic islets incorporated with 3H-labelled myo-inositol. Inositol
      phosphates, generated by the cleavage of phosphatidyl inositol by inositol
      phospholipase C, were analyzed using fast protein liquid chromatography. The
      islets were exposed to 3.3, 5.5 and 12 mmol 1(-1) glucose for 45 min in the
      absence or presence of 10, 20 or 30 mmol 1(-1) fructose, and the amount of
      insulin released into the medium was measured. Intracellular inositol phosphate
      accumulation was measured under the same glucose concentrations with 0, 10 and 30
      mmol 1(-1) fructose. As expected, fructose alone had no insulinotropic effect,
      but potentiated the glucose-induced (5.5 and 12 mmol 1(-1)) insulin secretion at
      concentrations of 10-30 mmol 1(-1). Glucose (12 vs. 3.3 mmol 1(-1)) significantly
      increased both intracellular content of inositol 1,4,5-trisphosphate, as well as
      its metabolite inositol 1,3,4-trisphosphate. Fructose, however, had no
      potentiating effects on the accumulation of inositol phosphates. It is therefore
      supposed that glucose does not activate inositol-specific phospholipase C via the
      glycolysis. Further, since fructose did not activate inositol-specific
      phospholipase C, this stimulation is likely to be induced by glucose as such.

PMID- 8743106
TI  - Qualitative assessment of intrathecal IgG synthesis by isoelectric focusing and
      immunodetection: interlaboratory reproducibility and interobserver agreement.
AB  - Detection of intrathecal IgG synthesis is important in patients with suspected
      multiple sclerosis (MS). The recommended method for the detection of intrathecal
      synthesis of IgG is isoelectric focusing and immunodetection of oligoclonal
      bands. Recently "The Committee for European Concerted Action for Multiple
      Sclerosis" has recommended that the results of isoelectric focusing for the
      detection of intrathecal synthesis of oligoclonal bands should not only be stated
      as positive or negative for intrathecal synthesis; instead, the laboratory should
      provide a detailed description of the IgG pattern in both cerebrospinal fluid
      (CSF) and serum together with a conclusion concerning the presence of intrathecal
      synthesis. We studied the interlaboratory reproducibility and interobserver
      agreement of isoelectric focusing, and the recommended classification system for
      the assessment of intrathecal IgG synthesis, in two separate patient groups
      employing kappa statistics. We found a high degree of interlaboratory
      reproducibility (133 patients; kappa = 0.95 +/- 0.05) and interobserver agreement
      (356 patients; kappa = 0.97 +/- 0.04) when the presence or absence of intrathecal
      IgG synthesis was assessed. The agreement was less pronounced, although still
      fully satisfactory, when the results were classified according to the detailed
      system by two laboratories (133 patients; kappa = 0.86 +/- 0.08) and two
      observers (356 patients; kappa = 0.88 +/- 0.08). Two specific problems in the
      interpretation of isoelectric focusing patterns were identified: one related to
      the discrimination of a pattern with several closely spaced bands which may
      represent a monoclonal protein; the other related to determining whether systemic
      band synthesis was present. We conclude that isoelectric focusing and
      immunodetection is a very reproducible technique for the detection of intrathecal
      IgG synthesis. Well defined criteria and extensive standardization may, however,
      be necessary when more elaborate classification systems are employed.

PMID- 8743107
TI  - Interferon gamma production in whole peripheral blood culture in acute hepatitis
      B.
AB  - Interferon gamma (IFNg) production in whole peripheral blood (WPB) and
      mononuclear (MN) cell culture in acute hepatitis B (AHB) was compared. IFNg
      production was induced by phytogem agglutinin and measured in the cell
      supernatants of 14 AHB patients in the course of the disease. There were some up
      regulating factors of IFNg production that probably operated in WPB culture: the
      presence of autoerythrocytes as well as the low content of monocytes. Autoserum
      regulated IFNg production in a stage-dependent way: it decreased IFNg activity at
      the bilirubin peak in hepatitis B infection, but not in convalescence. In
      contrast, we did not find a serum blocking effect in the corresponding stage of
      acute hepatitis A. The nature of this serum blocking factor in AHB is unclear.

PMID- 8743108
TI  - Determination of aglycones of ginsenosides in ginseng preparations sold in Sweden
      and in urine samples from Swedish athletes consuming ginseng.
AB  - Recently developed gas chromatographic and gas chromatographic-mass spectrometric
      methods were used to characterize 17 different commercial ginseng preparations
      sold in Sweden. The contents of total ginsenosides per capsule or per tablet
      varied from 2.1 to 13.3 mg. Unlike the other preparations, a red ginseng and
      three liquid ginseng preparations (after releasing the sugar moieties from
      ginsenosides) were shown also to contain significant amounts of 20-epimers of
      20(S)-protopanaxadiol and 20(S)-protopanaxatriol as well as their corresponding
      24,25-hydrated compounds. In addition to the genuine and artificial sapogenins
      mentioned above, two epimeric pairs of prosapogenines (ginsenoside Rg3 and 20(S)
      Rg3, ginsenoside Rh1 and 20(R)-Rh1) were also found in the liquid formulations.
      These results suggest that hydrolysis, epimerization and hydration in the side
      chain of the aglycone moiety of ginsenosides may occur in the liquid formulations
      under weak acidic conditions (pH 3.0-3.5 with 9-10% of alcohol at room
      temperature). The new method was also used to determine the aglycones of
      ginsenosides in urine samples from Swedish athletes stating that they had
      consumed ginseng preparations within 10 days before urine collection. Out of the
      65 samples analysed, 60 were found to contain 20(S)-protopanaxatriol. The
      concentrations of 20(S)-protopanaxatriol ginsenosides varied from 2 to 35 ng ml-1
      urine. This is the first demonstration of uptake of ginsenosides in humans after
      oral administration of ginseng preparations.

PMID- 8743109
TI  - Plasma protein changes induced by two orally administered androgen derivatives.
AB  - Epostane is a synthetic 17 alpha-alkylated 5 beta-androstane derivative, active
      following oral administration and devoid of any apparent androgenic, estrogenic
      or antiestrogenic potency. Circulating concentrations of 13 different plasma
      proteins were measured in eight women before and after 2 and 4 weeks of daily
      oral intake of 600 mg of epostane. The results were compared with those
      previously found during administration of the same daily dose of danazol, a
      synthetic 17 alpha-alkylated androgen derivative with known androgenic/anabolic
      activity. Epostane significantly suppressed serum levels of sex hormone-binding
      globulin, pregnancy zone protein and thyroxin-binding globulin and increased the
      levels of transthyretin. Haptoglobins, plasminogen and transferrin showed minor
      and/or transient changes and the levels of high density lipoproteins, alpha2
      macroglobulin, albumin, C1-esterase inactivator, C3 complement and transcortin
      remained unaffected. The pattern of changes in plasma proteins was almost
      identical to that induced by administration of danazol, although the effects of
      epostane were somewhat weaker. Thus epostane is capable of inducing substantial
      changes in the pattern of steroid-sensitive plasma proteins in an androgen-like
      fashion despite its apparent lack of androgenic activity. The capacity of a
      steroid to induce such changes thus seems to be tied to the chemical structure
      rather than to the intrinsic hormonal activity of the molecule.

PMID- 8743110
TI  - Interactions of endotoxin with human blood cells and serum proteins.
AB  - Endotoxin interacts with several plasma protein systems and blood cells, causing
      release of a multitude of endogenous mediators that contribute to the
      pathophysiological process of sepsis. Binding of 125I-labelled
      lipopolysaccharide, LPS, to human blood in vitro showed that the major part of
      the 125I-LPS was recovered in plasma, whereas only small amounts were retained in
      washed suspensions of granulocytes, erythrocytes, monocytes and lymphocytes,
      respectively. Whole leukocyte preparations or isolated subpopulations incubated
      with 125I-LPS or fluorescein-conjugated LPS followed by autoradiography, flow
      cytometry or immunofluorescence microscopy showed unequivocally that monocytes
      bound much more LPS than did granulocytes and lymphocytes. Lipoprotein
      electrophoresis followed by autoradiography showed that 125I-LPS bound to all the
      purified lipoprotein fractions, which was also confirmed by gel filtration
      chromatography. These findings demonstrate that monocytes represent the most
      important blood cell for LPS binding and that radiolabelled LPS is able to bind
      to lipoproteins as well as to other serum constituents.

PMID- 8743111
TI  - The utility of single-strand conformation polymorphism (SSCP) analysis: results
      obtained in families with Fabry's disease.
AB  - Single-strand conformation polymorphism (SSCP) analysis is a widely used and
      relatively simple method for detection of sequence polymorphisms in DNA
      fragments. We have used this technique to screen the alpha-galactosidase gene,
      with the aim of identifying the disease causing mutations in families with
      Fabry's disease. Five single-base shift mutations were found, but a single base
      pair deletion could not be recognized by SSCP. The risk of mistaking a neutral
      polymorphism for a mutation is illustrated, and the utility as well as the
      limitations of SSCP in screening and diagnostic use are discussed.

PMID- 8743112
TI  - Correlations between fatty acid composition of the erythrocyte membrane and blood
      rheology data.
AB  - The fatty acid composition of erythrocyte membrane phospholipids (phosphatidyl
      choline, PC, and phosphatidyl ethanolamine, PE) and erythrocyte filterability was
      studied in seven subjects with type II diabetics before and after change of
      therapy from oral hypoglycaemic agents to insulin. For comparison the same
      variables were also studied in 10 healthy controls. In the diabetic group the
      greatest changes in fatty acid composition were found before treatment in the PE
      fraction, corresponding to the inner part of the red cell membrane. We found
      increased values for 16:0 (p < 0.001), 18:1 (p < 0.01) and 20:4 (omega-6) (p <
      0.05) and decreased values for 16:1 (p < 0.01) and 18:3 (omega-6) (p < 0.001),
      compared to values for the healthy controls. The proportion of fatty acids in the
      inner leaflet of the membrane did not correlate to the red cell filtrability in
      diabetics or healthy subjects. In the PC fraction, which corresponds to the outer
      leaflet of the erythrocyte membrane, we found higher values for 16:0 (NS), 18:1
      (p < 0.05), 20:4 (omega-6) (NS) and 22:5 (omega-3) (p < 0.01), and lower values
      for 16:1 (p < 0.05) in diabetics, compared to healthy controls. In the PC
      fraction an increased proportion of 16:0 was inversely correlated with red cell
      transit time (RCTT) (p < 0.05), and increased proportions of 16:1 and 18:0 were
      correlated with a high RCTT (p < 0.05). Insulin treatment did not significantly
      change red cell deformability or the fatty acid composition of the red cell
      membrane. Our results also indicate that palmitic acid (16:0) may be favourable
      in the PC fraction and stearic acid (18:0) unfavourable with respect to the
      rheological properties of erythrocytes.

PMID- 8743113
TI  - Absence of heparin interference in the measurement of aspartate aminotransferase
      activity with the Ektachem AST "visible" slides.

PMID- 8743114
TI  - Triangles and tribulations: the politics of Nazi symbols.
AB  - This article explores the politics of "reclamation." Its focus is on pink and
      black triangles, currently used as symbols for gay and lesbian pride and
      liberation. Previously, these same identifiers were worn by those destined for
      annihilation during the Holocaust. I suggest that, in [re]claiming these markers,
      activists, however well intentioned, run a path dangerously close to the denial
      of history.

PMID- 8743115
TI  - "Physical attractiveness stereotype" and the attribution of homosexuality
      revisited.
AB  - The present study investigated whether subjects would perceive male and female
      faces as homosexual based upon facial attractiveness while statistically
      controlling for facial masculinity/femininity. Also of interest was the extent to
      which the subjects' gender and attitudes toward homosexuality would influence
      their perceptions. Eighty undergraduates indicated how likely they thought it was
      that six male and six female faces were homosexual. The targets were also rated
      on attractiveness and masculinity/femininity. The present sample also completed
      the Index of Homophobia, the Bem Sex Role Inventory, the Attitude Toward Women
      Scale, a conservatism scale, and a demographic questionnaire. The subjects
      assigned higher homosexuality ratings to the unattractive males and females
      compared to their attractive counterparts. Gender of subject and attitudes toward
      homosexuality did not significantly affect evaluations.

PMID- 8743116
TI  - Identity formation for lesbian, bisexual, and gay persons: beyond a
      "minoritizing" view.
AB  - There is considerable controversy regarding the means by which lesbian, gay, and
      bisexual persons achieve a sense of sexual identity. In this paper, the concepts
      of identity and sexual identity are reviewed, and the literature on lesbian and
      gay "coming out" processes are critiqued. Major limitations of these studies
      include their narrow samples, their narrow focus on sexuality, their linear
      nature, and their lack of attention to the larger sociohistorical context. They
      tend to "minoritize" sexual identities. A more comprehensive cyclical model of
      identity development would put sexual identity into a context that includes other
      important facets of identity such as gender, race, and class-a more
      universalizing approach.

PMID- 8743117
TI  - Drug and alcohol use among lesbian and gay people in a southern U.S. sample:
      epidemiological, comparative, and methodological findings from the Trilogy
      Project.
AB  - The Trilogy Project is a longitudinal study of lesbian and gay people living in
      and around two metropolitan areas in a southern state. The study was specifically
      designed to provide (1) epidemiological data on the lifetime, past year, and past
      month prevalence rates for the use of 6 illicit, 4 psychotherapeutic, and 2 licit
      drugs, and (2) comparative data to the National Household Survey on Drug Abuse
      (NHSDA). Self-report data were collected on 1067 respondents using multiple
      sampling strategies and a research design that yielded response rates averaging
      over 50%. Results indicated some age group differences in the prevalence of
      certain drugs by gay men compared to lesbians. When comparisons were made to the
      NHSDA, Trilogy Project respondents were found to have significantly higher
      prevalence rates for the past year use of marijuana, inhalants, and alcohol but
      not cocaine. While lesbian and gay people drink alcohol more frequently during
      the month than NHSDA respondents, few differences occurred between the two
      samples for heavy alcohol consumption. Research questions suggested by the data
      and theoretical directions for future research are discussed.

PMID- 8743118
TI  - The prevalence of victimization and its effect on mental well-being among lesbian
      and gay people.
AB  - Research on victimization among oppressed groups such as lesbian and gay people
      has provided limited insight into its impact on the lives of those who are
      frequently targeted. This is due in part to small sample sizes and the absence of
      significant variables known to influence mental well-being. This analysis
      examines the prevalence and effects of victimization on a large sample (N = 1067)
      of lesbians and gay men living in a southern state. Multiple regression is used
      to determine the psychological consequences of victimization as measured by
      depression. Additional factors thought to contribute, either positively or
      negatively, to the effect of victimization on mental well-being, i.e., social
      support, self-esteem, external stress, and internalized homophobia, are also
      included in the analysis. Results indicate that victimization has a significant
      positive effect on depression for both lesbians and gay men when controlling for
      other variables. Self-esteem was found to be the strongest predictor of
      depression for the entire sample. Social support was found to have a similar
      effect for lesbians and gay men with partner support and having no support being
      significant. Gender differences were found for measures of external stress,
      internalized homophobia, and age.

PMID- 8743119
TI  - Genetics of tumour necrosis factor in systemic lupus erythematosus.

PMID- 8743120
TI  - SLE and osteoporosis: dependence and/or independence on glucocorticoids.

PMID- 8743121
TI  - Accuracy of 133-xenon regional cerebral blood flow and quantitative
      electroencephalography in systemic lupus erythematosus.
AB  - OBJECTIVE: Comparative assessment of sensitivity and specificity of regional
      Cerebral Blood Flow (rCBF) by 133-Xenon inhalation and quantitative
      Electroencephalography (qEEG) in patients with Neuropsychiatric Systemic Lupus
      Erythematosus (NP-SLE). METHODS: Sixty-two combined rCBF and qEEG examinations
      were performed in fifty-two SLE patients. Group A: 27 SLE patients without NP
      SLE; group B: 17 patients with florid (within 1 month) NP-SLE; group C: 12
      patients previous NP-SLE examined in the remission phase (four patients of which
      already considered in group B). The study also included data deriving from two
      sets of examinations in ten patients who were observed twice, in different phases
      of the clinical course of NP-SLE. RESULTS: In comparison to healthy controls,
      rCBF lower (p < .001) in group B only, whereas qEEG showed similar increases of
      both delta and theta relative powers together with a reduction of alpha relative
      power in groups A-C. As compared to group A, sensitivity and specificity in
      detecting cerebral abnormalities in group B were 76% and 78% for rCBF, and 59%
      and 44% for qEEG, respectively. In the ten patients examined twice, rCBF was
      consistent with clinical course in 90% of cases and qEEG in 60%. CONCLUSION:
      Total accuracy in detecting cerebral functional abnormalities during florid NP
      SLE is better by rCBF than by qEEG. rCBF and, in selected cases, qEEG
      examinations are reliable markers of NP-SLE.

PMID- 8743122
TI  - Establishment and characterization of permanent human endothelial cell clones.
AB  - Though vasculitic diseases have been claimed to be associated with anti
      endothelial cells antibodies (AECA), there is a widespread awareness of the
      limitations of the tests currently in use. Our objective was therefore to
      establish clones, in the hope that some of them would express disease-specific
      membrane autoantigens. Two EC lines and 7 clones were established by fusing human
      umbilical vein EC with epithelial A549/8 cells, and cloning by limiting dilution.
      An additional clone was derived from the EA.hy 926 cell line. All clones carried
      EC markers, such as thrombomoduline (TM) and platelet-EC adhesion molecule 1 but
      differed from each other, depending on whether they expressed HLA class II
      antigen, LFA-1, thrombospondin receptor or von Willebrand factor (vWf) antigen.
      Clones were also characterized by their ability to release tissue plasminogen
      activator, interleukin 6, TM and vWf. This panel is meant to distinguish
      reactivities of AECA.

PMID- 8743123
TI  - Factors associated with fetal losses in severe systemic lupus erythematosus.
AB  - We evaluated factors associated with fetal losses in patients with severe lupus
      in a nested case-control study. We assessed separately 73 pregnancies that
      occurred in 46 women from a cohort of 633 Systemic Lupus Erythematosus (SLE)
      patients. They had at least one pregnancy after SLE diagnosis, one or more of our
      severity criteria and all had taken immunosuppressive drugs. Included data were
      related to disease severity, anti-phospholipid syndrome (APS), anticardiolipin
      antibodies (a-CL ab), and drugs received during pregnancy. Cases were pregnancies
      with fetal wastage; controls were pregnancies with live-born children. The mean
      age at pregnancy was 26.6 +/- 4.5 years. Cases had longer disease duration, 6.1
      +/- 3.5 years vs 4.5 +/- 4.3 of controls (p = 0.02); higher prevalence of renal
      involvement, hemolysis and recurrent venous thrombosis (p < 0.05); they also
      tended to have a greater prevalence of a-CL ab, and previous fetal losses (p =
      0.06). Cases used azathioprine more frequently than controls (p = 0.04).
      Univariate analysis showed an association of renal involvement, hemolytic anemia,
      azathioprine or cyclophosphamide prescription during pregnancy, previous fetal
      losses and APS with fetal wastage. Immunosuppressive drugs and the APS remained
      significant in the multivariate analysis (p = 0.05; F = 0.01). Factors related
      with fetal losses in women with severe SLE were: longer disease duration,
      ingestion of immunosuppressive drugs during pregnancy and any related
      manifestation of APS. We did not find macroscopic malformations in live-children
      of women that took azathioprine during pregnancy.

PMID- 8743124
TI  - Antibodies reactive with HIV-1 antigens in systemic lupus erythematosus.
AB  - Antibodies reactive with retroviral gag proteins have been detected in patients
      with systemic lupus erythematosus (SLE). We investigated the immune responses
      against human immunodeficiency virus (HIV) 1 antigens in the sera of 44 Turkish
      patients with SLE. Serum samples were tested by using two different commercial
      enzyme immunoassay (EIA) kits and by Western blotting. EIA studies revealed
      positive results in 12 patients (27%) for HIV-1 antigens by one of the kits that
      coated with purified viral antigens. Immunoblot analysis showed antibodies mainly
      to retroviral gag proteins in 23 patients (52%). The most frequent reactivity was
      against the p18 gag protein (n = 9). Although antibodies reactive particularly
      with p24 antigen were described in the previous reports, antibodies to p24 were
      found in only two patients. These findings might reflect a serologic diversity in
      different ethnic groups and also suggest the involvement of different triggers in
      the etiopathogenesis of SLE.

PMID- 8743125
TI  - Brain calcification in patients with cerebral lupus.
AB  - Cerebral lupus (CL) is a common cause of morbidity and mortality in patients with
      SLE. The brain CTs of 27 consecutive adult patients with SLE and various
      neurological presentations were reviewed. The median age and duration of
      neurological symptoms at the time of the brain CT were 30 years (range = 14-51
      years) and six days (range = 1 day-22 years), respectively. Eleven patients (41%)
      had normal CTs. The abnormalities in the remaining patients could be divided into
      six categories: (a) cerebral atrophy alone (two patients); (b) calcification
      alone (three patients); (c) infarct(s) alone (five patients); (d) cerebral
      atrophy and calcification (three patients); (e) cerebral atrophy and infarct(s)
      (one patient) and (f) cerebral atrophy, calcification and infarct(s) (two
      patients). Altogether eight patients (30%) (age range = 17-47 years) had
      intracerebral calcification: the globus pallidus was involved in all, putamen in
      two, head of the caudate nucleus in one, thalamus in one, centrum semiovale in
      two and cerebellum in three patients. Two patients had extensive calcifications
      of most of the basal ganglia, centrum semiovale and cerebellum. There was no
      relationship between the presence/degree of calcification and age of
      patients/duration or type of neurological presentation. The pathogenesis of
      cerebral calcification in CL is unknown. Cerebral lupus must now be included in
      the differential diagnosis of intracerebral calcification.

PMID- 8743126
TI  - Abnormal prostanoid metabolism in lupus nephritis and the effects of a
      thromboxane A2 synthetase inhibitor, DP-1904.
AB  - Abnormalities of prostanoid metabolism, which may affect renal function, were
      studied in lupus nephritis. The subjects were 31 patients with lupus nephritis,
      ten with non-renal SLE, and four with renal, non-SLE collagen disease. Urinary
      levels of various prostanoids, thromboxane B2(TXB2), 11-dehydro-TXB2, 6-keto-PGF1
      alpha,2,3-dinor-6-keto-PGF1 alpha and PGE2, and plasma level of 11-dehydro-TXB2,
      were determined. The effects of four days' dosing of a selective thromboxane A2
      (TXA2) synthetase inhibitor, DP-1904 (DP), on prostanoid metabolism, were also
      studied. Urinary excretion of TXB2, which reflects the renal production of TXA2,
      was significantly increased in patients with lupus nephritis as compared with non
      renal SLE (p < 0.05). The urinary TXB2/6-keto-PGF1 alpha ratio was also increased
      in lupus nephritis as compared with non-renal SLE or healthy controls (p < 0.01),
      indicating a prostanoid imbalance, which may lead to impaired renal function and
      subsequent pathology. The urinary TXB2/6-keto-PGF1 alpha ratio in these lupus
      nephritis patients showed negative correlations with Ccr and positive
      correlations with anti-DNA antibody titer (p < 0.001). DP was administered orally
      (400 mg/day, given in two divided doses) for four days to eight lupus nephritis
      patients. The urinary excretion of TXB2 and urinary TXB2/6-keto-PGF1 alpha ratio
      were decreased after one to two days of treatment in all patients. An increase in
      creatinine clearance used as a measure of renal function was observed in four of
      eight patients. Furthermore, no side effects were elicited during the four days
      of treatment. The conclusion reached were that the abnormal prostanoid metabolism
      observed in lupus nephritis could aggravate renal function through hemodynamic
      mediation, and that the deviated metabolism was reversible and, at least
      partially, corrected by a TXA2 synthetase inhibitor.

PMID- 8743128
TI  - Pneumonitis in a lupus twin pregnancy: a case report.
AB  - We describe a patient with systemic lupus erythematosus (SLE), whose pregnancy
      was complicated by fulminant lupus pneumonitis and pericarditis. Maternal disease
      responded to therapy and twin girls were delivered, both with thrombocytopenia,
      one of whom died of an intraventricular haemorrhage. Pneumonitis is a rare
      complication of lupus in pregnancy which may be fatal. We suggest patients with
      previous severe pneumonitis should have lung function tests at the onset of
      pregnancy, and treatment be modified to suppress flare if there is any indication
      of severe pneumonitis in early pregnancy.

PMID- 8743127
TI  - In vitro type-1 and type-2 cytokine production in systemic lupus erythematosus:
      lack of relationship with clinical disease activity.
AB  - OBJECTIVE: To investigate the relationship between disease activity and in vitro
      cytokine, soluble(s)CD23 and polyclonal and anti-DNA antibody production by PBMC
      from patients with active systemic lupus erythematosus (SLE). METHODS: Cytokines,
      sCD23 and immunoglobulins were estimated by ELISA in unstimulated and polyclonal
      mitogen-stimulated culture supernatants. RESULTS: PHA-induced IL-2 and IFN-gamma
      production were decreased, whereas spontaneous and PHA-induced IL-6 and IL-10
      production were increased in cultures of SLE lymphocytes. Conversely, spontaneous
      and PHA-stimulated IL-4 and sCD23 production was comparable between patients and
      controls. Finally, we found an increase in in vitro spontaneous polyclonal and
      anti-DNA IgG secretion. CONCLUSIONS: We demonstrated an expanded type-2 cytokine
      profile with no correlation with parameters of disease activity.

PMID- 8743129
TI  - The role of beta 2-glycoprotein I in the antiphospholipid syndrome.
AB  - Antiphospholipid antibodies were originally thought to bind negatively-charged
      (anionic) phospholipids. Current evidence suggest that the target antigen is
      considerably more complex and includes beta 2-glycoprotein I, a phospholipid
      binding plasma protein. Our understanding of the pathophysiology of the
      antiphospholipid syndrome has increased exponentially with a number of studies
      into the interactions of antiphospholipid antibodies and beta 2-glycoprotein I.

PMID- 8743130
TI  - Immunology of antiphospholipid antibodies and their interaction with plasma
      proteins.
AB  - 'Antiphospholipid' (aPL) antibodies are of clinical importance because of their
      strong association with vascular thrombosis, recurrent pregnancy loss,
      thrombocytopenia and other clinical manifestations like livedo reticularis,
      chorea and cardiac valvular disease. While aPL antibodies have traditionally been
      thought to be directed against negatively-charged (anionic) phospholipids current
      evidence suggests that these autoantibodies recognise protein-phospholipid
      complexes or the proteins themselves. A number of candidate proteins have been
      investigated with the two most extensively researched being beta 2-glycoprotein I
      and prothrombin.

PMID- 8743131
TI  - Anticardiolipin antibodies and beta 2-glycoprotein I.

PMID- 8743132
TI  - Pharmacological intervention in antibody mediated disease.
AB  - The use of single signal anergy to inactive pathological B cells in an antigen
      specific manner is discussed. Cross-linking surface immunoglobulin, with a
      construct which contains oligovalent B cell epitopes on a non-immunogenic
      molecular framework can be used to inactivate the target B cells if the construct
      lacks T cells epitopes. An example of such a B cell toleragen is LJP 394, which
      inactivates anti-dsDNA-specific B cells in vivo in murine immunized and
      spontaneous disease models. The drug enhances survival and lowers renal pathology
      in BXSB mice. Appropriate definition of epitopes of pathological (auto)
      antibodies thus offers an opportunity for pharmacological intervention.

PMID- 8743133
TI  - Laboratory detection of antiphospholipid antibodies.
AB  - 'Antiphospholipid' (aPL) antibodies are a heterogenous group of autoantibodies
      that are now considered to be directed mainly to plasma proteins or protein
      phospholipid complexes. Standardisation of assays for anticardiolipin (aCL)
      antibodies and lupus anticoagulants (LA) have been fraught with difficulty
      despite numerous attempts to perform this by International Standardisation
      Workshops and Committees.

PMID- 8743134
TI  - Antiphospholipid antibodies and thrombosis: assessment of the potential risk for
      thrombosis.

PMID- 8743135
TI  - Clinical manifestations and management of the antiphospholipid syndrome.
AB  - Since the original description of associations between lupus anticoagulant and
      anticardiolipin antibodies with thrombosis, fetal loss and thrombocytopenia,
      several distinct clinical manifestations related to this so-called
      antiphospholipid syndrome have appeared in the literature. Retrospective studies
      indicate that long-term treatment with oral anticoagulants can effectively reduce
      the chance of recurrent thrombosis. However, data from controlled prospective
      studies are urgently needed to enable optimal counselling of patients suffering
      from this syndrome.

PMID- 8743136
TI  - Neurological and obstetric manifestations of the antiphospholipid syndrome.
AB  - The experience of a single centre with the neurological and obstetric
      complications of the antiphospholipid syndrome is presented and reviewed briefly
      with the general world literature. Both the neurologic and the obstetric
      manifestations exemplify the need for a greater understanding of underlying
      pathogenetic mechanisms and a more rigorous approach to therapy.

PMID- 8743137
TI  - Current studies on human implantation: a brief overview.
AB  - Embryo implantation involves a series of complex interactions between the
      developing embryo and the maternal endometrium. Results of studies with animal
      models suggest that the uterus must undergo a series of morphological and
      biochemical changes, mediated primarily by oestrogen and progesterone, before it
      becomes receptive for successful implantation. At present there is little
      understanding of the endometrial changes required to achieve endometrial
      receptivity for implantation in the human. It appears that control of receptivity
      is not as stringent in the human as in some other species, with IVF data
      suggesting that the duration of receptivity is at least 4 days, and that
      successful implantation can occur under a relatively wide range of morphological
      and ultrastructural conditions. Research on the later stages of implantation,
      including embryo positioning within the uterus, attachment and invasions, has
      been almost non-existent in the human. Further studies are critical for a better
      understanding of this complex process, although human studies will always be
      limited by ethical constraints.

PMID- 8743138
TI  - Control of placental blood flow: workshop report.

PMID- 8743139
TI  - Regulation of human placental fetal vessel tone: role of nitric oxide.
AB  - Factors affecting fetal vessel resistance have been studied in vitro in
      bilaterally perfused lobules of human placentae. Potent and efficacious
      constrictors in this preparation (in order of potency) include endothelin-1 > the
      thromboxane mimetic U46619 > endothelin-3 > prostaglandin F2 alpha. Inhibitors of
      eicosanoid synthesis did not affect fetal vessel basal perfusion pressure, nor
      did they potentiate the effects of the vasoconstrictor U46619. In contrast, the
      nitric oxide inhibitors N omega-nitro-L-arginine (NOLA), haemoglobin and
      methylene blue all increased fetal vessel basal perfusion pressure and also
      increased U46619-induced constriction. Similarly, NOLA markedly potentiated the
      constrictor effects of endothelin-1, angiotensin II, 5-hydroxytryptamine and
      bradykinin. These studies therefore provide evidence that NO is important in the
      maintenance of low basal fetal vessel impedance and also reduces the effects of a
      number of vasoconstrictor autacoids. Nitric oxide synthase (NOS) activity of
      human placental homogenates has been measured and shown to be mainly calcium
      dependent. Human placental NOS activity was not affected by labour state but was
      reduced in pre-eclampsia. No evidence was found that in pre-eclampsia raised
      concentrations of the endogenous NOS inhibitor asymmetric dimethylarginine were
      responsible for the reduced placental NOS activity. Hence, these studies provide
      evidence that NO is an important endogenous dilator of the fetal vessels of the
      human placenta and that reduced NOS activity could contribute to the pathogenesis
      and/or effects of pre-eclampsia.

PMID- 8743140
TI  - Screening for Down syndrome in the first trimester.
AB  - Second-trimester maternal serum screening for Down syndrome is now well
      established, and permits detection of up to 70% of cases. The disadvantage of
      this sort of screening is that the timing of maternal blood sampling is
      relatively late (after 15 weeks). There is an accumulating body of evidence to
      suggest that in the first trimester concentrations of a number of pregnancy
      associated proteins and hormones differ in chromosomally normal and abnormal
      pregnancies. A first-trimester maternal serum screening test for Down syndrome
      may therefore be possible. In addition, new methods of screening have recently
      been described based on ultrasound findings at 11 to 13 weeks of gestation. This
      review article presents a discussion of published data on the feasibility of
      first-trimester screening for Down syndrome.

PMID- 8743141
TI  - Pregnancy-associated plasma protein A (PAPP-A): measurement by highly sensitive
      and specific enzyme immunoassay, importance of first-trimester serum
      determinations, and stability studies.
AB  - It has recently been established that maternal serum pregnancy-associated plasma
      protein A (PAPP-A) was reduced in pregnancies with fetal Down syndrome in the
      first but not in the second trimester of gestation. In comparison with two other
      placental proteins, human chorionic gonadotrophin and pregnancy-specific beta 1
      glycoprotein, an explanation for this can be formulated based on the large
      molecular weight of PAPP-A. With the increasing clinical demand for fetal
      abnormalities to be diagnosed in the first rather than in the second trimester of
      pregnancy, maternal serum PAPP-A is a strong potential candidate for being used
      in routine trisomy screening. We have developed a sensitive enzyme immunoassay
      (ELISA) intended at smaller laboratories due to its long shelf life. Here we show
      that repeated freezing and thawing, or the addition of iodoacetate (5 mM) did not
      affect the results, at both high or low concentration of PAPP-A. It is also
      possible to introduce the serum into the test as a dry sample on blotting paper,
      easily posted in an envelope. A decrease of 21% was observed after such dry
      storage for three weeks at room temperature, which can be compensated for by the
      inclusion of a dried control serum, mailed with the sample(s).

PMID- 8743142
TI  - Cellular localization of glucose transporter messenger RNA in human placenta.
AB  - High levels of expression of the glucose transporter (GLUT) isoforms 1 and 3 have
      been demonstrated in the human placenta by Northern blotting. However, the
      cellular localization of placental GLUT mRNA has not been described. Furthermore,
      recent preliminary kinetic data indicate that GLUT 2 might be present in
      syncytiotrophoblast. Human placental tissue from preterm (16-22 weeks) and term
      pregnancies was collected for identification and localization of glucose
      transporter mRNA. Following paraffin embedding, sections were cut and in situ
      hybridization was performed with fluorescein-labelled cRNA. In addition,
      immunoblotting and immunocytochemistry were carried out using an anti-GLUT 2
      antibody. GLUT 1 mRNA was highly expressed in syncytiotrophoblast cells at term.
      GLUT 1 expression was much less abundant in non-syncytial cells. In contrast,
      GLUT 3 mRNA was present in lower amounts and more evenly distributed between
      syncytial and other placental cells. GLUT 1 mRNA was also highly abundant in
      preterm syncytiotrophoblast. The cellular distributions of GLUT 1 and GLUT 3 mRNA
      in the preterm placentas were similar to those in term tissue. With regard to
      GLUT 1, these findings correlate well with cellular localization and gestational
      development of GLUT 1 protein. No GLUT 2 protein was detected. It is concluded
      that GLUT 1 is the main isoform involved in transplacental glucose transport in
      the human.

PMID- 8743143
TI  - Interaction between pregnancy-induced bioactive peptides and the placental
      proteases.
AB  - Studies have shown that placental proteases metabolize vasoactive peptides,
      possibly derived from the fetus, and protect the exchange of peptide hormones
      across the placenta in order to maintain feto-placental homeostasis. Changes in
      maternal serum protease activities were useful for monitoring pre-eclampsia and
      predicting the onset of labour. The study showed that possible role of
      oxytocinase in the maintenance of gestation and the possible involvement of
      angiotensinase in the attenuated pressor responses to angiotensin II during
      pregnancy, respectively. In addition, the ratio of peak systolic over least
      diastolic pressure (S/D) of uterine or umbilical artery assessed by the Doppler
      technique was closely correlated with the concentrations of maternal serum
      proteases in pre-eclampsia, which suggested that placental proteases might
      control utero-placental circulation via the regulation of concentrations of
      vasoactive peptides in uteroplacental circulation.

PMID- 8743144
TI  - Interrelationships between the renin angiotensin system and uteroplacental blood
      flow--a recent perspective.
AB  - In pregnancy, the maternal circulating renin-angiotensin system (RAS) and
      uteroplacental tissue RAS has been thought to support maternal placental flow by
      raising maternal arterial pressure or changing placental vascular resistance.
      Also, the placenta or uterus may alter maternal circulating RAS. Recent studies
      in the authors' laboratory using chronically catheterized rabbits are compared
      with previous studies on interactions between the RAS and uteroplacental flow.
      When uterine driving pressure was reduced either mechanically or after converting
      enzyme inhibition, maternal placental flow decreased in proportion to change in
      driving pressure; myoendometrial flow did not change. Angiotensin II (AII)
      infusion to increase pressure by 21 +/- 2 mm Hg decreased placental but not
      myoendometrial flow. Thus, there is no evidence that maternal placental flow is
      autoregulated or supported by a specific renin-angiotensin mechanism. Normally,
      there is no net uterine release or uptake of active plasma renin activity, AI, or
      AII, but there is a small net release of trypsin-activated plasma renin activity
      (tPRA), presumably prorenin. Distal aortic occluder inflation produced upper-body
      hypertension, and uterine release of tPRA increased. There was a significant
      uterine arteriovenous concentration difference for AII during AII infusion. These
      methods are adaptable for studying interactions between uteroplacental flow and
      other vasoactive agents.

PMID- 8743145
TI  - Recent advances in placental peptide research: workshop report.

PMID- 8743146
TI  - Advances in understanding permeability in fetal capillaries of the human
      placenta: a review of organization of the endothelial paracellular clefts and
      their junctional complexes.
AB  - A review is presented of the evidence that the capillaries of the fetal-placental
      circulations of man and the guinea-pig are typical members of class of continuous
      non-brain capillaries. Their permeability is similar to that of muscle
      capillaries, and there is much evidence that the main permeation route for
      hydrophilic solutes in capillaries of this class is through the paracellular
      clefts of the endothelium. The properties of this paracellular route are based on
      discontinuous tight junctions which may serve to restrict the fraction of the
      paracellular cleft available to solutes, and on a molecular sieve which may be
      based on arrays of adhesion molecules in the zonula adhaerens of the junctional
      complex. The characteristics of this paracellular route and of overall
      microvascular permeability in these types of placenta make it clear that fetal
      capillaries form a significant component of the total transplacental permeability
      restriction.

PMID- 8743147
TI  - Molecular approach to intrauterine growth retardation: an overview of recent
      data.
AB  - Consideration of the abnormal regulation of fetal growth leading to intrauterine
      growth retardation must take account of the fundamental differences between the
      regulation of growth before and after birth. The significance of endocrine
      regulators of growth differs greatly in utero. During the first trimester of
      pregnancy, embryonic growth might be controlled at the level of the individual
      organs by nutrient supply and by locally active growth factors. Later, fetal
      growth depends essentially upon materno-placental cooperation in delivering
      nutrients to the fetus. Therefore the major role of hormones in fetal growth is
      to mediate utilization of available substrate. Fetal growth seems to be regulated
      by fetal insulin, IGF-1 and certainly IGF-2, while growth hormone has only a
      secondary role to play. In late gestation, placental size and fetal growth rate
      are well correlated, pointing to a key role of the placenta in the regulation of
      fetal growth. It is therefore of importance to understand the molecular
      mechanisms involved in regulating placental development and endocrine functions.
      TGF alpha and EGF might play a major role as suggested by the modulation of their
      receptors with placental development, and by the specific alterations of
      epidermal growth factor receptors in intrauterine growth retardation. In
      addition, human placenta secretes specifically placental growth hormone. The
      concentration of placental growth hormone is significantly decreased in sera of
      pregnant women bearing a fetus with intrauterine growth retardation.

PMID- 8743148
TI  - Role of epidermal growth factor (EGF) and its receptor in the development of the
      human placenta.
AB  - To elucidate the role of EGF in human placental development, effects of EGF on
      the proliferation and differentiation of trophoblasts were investigated. Explants
      of trophoblastic tissues obtained from 4-5 week or 6-12 week placentas were,
      respectively, cultured with or without EGF, in the presence or absence of triiodo
      L-thyronine (T3) in a serum-free condition. The proliferative activity was
      examined by immunocytochemical staining with an antibody Ki-67, and the
      differentiated function was assessed by the ability to secrete human chorionic
      gonadotrophin (hCG) and human placental lactogen (hPL). In 4-5 week placentas,
      EGF and EGF receptor were localized in cytotrophoblast (C-cell), and EGF
      augmented the proliferation of C-cell without affecting the ability to secrete
      hCG and hPL. In contrast, in 6-12 week placentas, EGF and EGF receptor were
      localized in syncytiotrophoblast (S-cell), and EGF stimulated the secretion of
      hCG and hPL without affecting the proliferation of C-cell. In situ hybridization
      with c-erb B probe revealed that c-erb B mRNA is expressed in the S-cell after 6
      weeks' gestation. Column chromatography of the serum-free media obtained by 5-day
      culture of early placental tissues resulted in the elution of immunoreactive EGF.
      The addition of T3 (10(-8) mol L(-1)) resulted in increased secretion of
      immunoreactive EGF by placental explants. These findings suggest that EGF acts as
      an autocrine factor in regulating early placental growth and function in synergy
      with thyroid hormone.

PMID- 8743149
TI  - Secretory type II phospholipase A2 and the generation of intrauterine signals.
AB  - Recent advances in the understanding of the metabolism of cell membrane
      glycerophospholipids and the subsequent generation of biologically active
      metabolites have provided new insight into their role in normal spontaneous-onset
      labour and delivery at term, and in preterm labour. In particular, multiple
      isozymes of the lipolytic enzyme phospholipase A2 (PLA2) have been identified in
      human gestational tissue during late pregnancy and at the time of labour.
      Specific isozymes have been identified that are active intracellularly (e.g.
      cytosolic PLA2) or extracellularly (e.g. Type II and Type IV secretory PLA2). The
      relative contribution of these isozymes to total PLA2 activity is tissue specific
      and affected by labour status. The development of isozyme-specific inhibitors of
      PLA2 may afford the opportunity to better regulate the formation of biologically
      active phospholipid metabolites within intrauterine compartments. With the
      identification of secretory PLA2 isozymes in human gestational tissues, a new
      pathway for materno-fetal and/or intrauterine communication has been established-
      a pathway in which secretory PLA2 isozymes released by intrauterine tissues act
      in an autocrine, paracrine or even endocrine fashion to affect
      glycerophospholipid metabolism, cell membrane fluidity and the generation of
      biological mediators.

PMID- 8743150
TI  - Oxytocin in human intrauterine tissues at parturition.
AB  - The recent detection of oxytocin (OT) mRNA in human gestational tissues suggests
      that OT may be locally synthesized and released to act on the uterus as a local
      mediator in the mechanism of parturition. In order to investigate this
      possibility the OT immunoreactive (I.R.) content was examined directly in
      placental decidua and amniochorial membranes after term and preterm delivery and
      in their culture media at term gestation. I.R.OT concentrations were also
      measured in maternal, retroplacental and umbilical plasma as well as in amniotic
      fluid in the presence or the absence of labour. Low I.R.OT concentrations (below
      15 fmol g-1 wet tissue) were found in both amniochorial membranes and placental
      decidua. Moreover, whereas in amniochorion they were higher (P < 0.05) after
      preterm than term spontaneous parturition, in decidua they were higher (P < 0.05)
      after term than preterm vaginal delivery. Detectable amounts (below 15 fmol g-1
      wet tissue per h) of I.R.OT were also found in culture media from explants of the
      above tissues. Among all the examined maternal and fetal fluids a rise in I.R.OT
      content at parturition was detected only in the amniotic liquor (P < 0.05). These
      findings suggest that I.R.OT concentrations in intrauterine tissues are very low;
      however, considering that OT is the most potent endogenous uterotonic agent, OT
      as such concentrations might play a paracrine function in the biochemical events
      leading to human parturition. Therefore, a role for amniotic OT in parturition
      can not be excluded.

PMID- 8743151
TI  - Drug delivery during pregnancy: evaluation in vitro of new drugs.
AB  - Indications for the treatment of the pregnant woman fall into three general
      categories: mother and infant require treatment, only the mother should be
      treated, or only the infant. Directing therapy towards the affected subject is an
      important aspect of good care, although it is not the only one. It is argued that
      a rational selection of the appropriate drug can be made without endangering
      mother or infant, with the aid of select laboratory investigations, including
      placental perfusion, and a knowledge of placental physiology. Examples are
      presented to support this contention. The intra-amniotic administration of drugs
      is briefly discussed. A plea is made to develop drugs that are designed
      specifically for use during pregnancy.

PMID- 8743152
TI  - Influence of organic cations on basic amino-acid uptake by human placental villi.
AB  - Human placental chorionic villi were incubated for 30 min with [3H]lysine or
      [3H]arginine and the distribution ratios (intracellular:extracellular
      concentrations) were determined. The ratios remained unchanged when Na+ in
      Earle's buffered salt solution was replaced with Li+. When Na+ was replaced with
      choline there was a significant increase is distribution ratios (lysine 1.34 +/-
      0.33 v. 3.99 +/- 0.15, arginine 1.95 +/- 0.37 v. 5.05 +/- 1.16). Leucine, a
      neutral amino acid with a Na(+)-independent transport system, was unaffected by
      choline substitution. The distribution ratio for alanine, which is Na(+)
      dependent, was reduced (2.50 +/- 0.41 v. 1.45 +/- 0.20). Two other quarternary
      amines, acetyl-beta-methylcholine and tetraethylammonium chloride (TEA) caused
      similar increases in the distribution ratios of the basic amino acids. Hordenine,
      a tertiary amine, was less effective and there was little or no effect with
      ephedrine, a secondary amine. The choline effect was first observable at
      concentrations of 105 mM. With TEA, there was a progressive increase in
      distribution ratios beginning at 29 mM. Lysine efflux was measured after
      incubation of villi with lysine in Earle's buffer or choline buffer. Lysine was
      rapidly released to the fresh medium with 25% more retained in choline-exposed
      villi. The amines may cause alterations in the kinetics of basic amino-acid
      transporters or may modify other aspects of placental physiology permitting an
      increase retention of the basic amino acids.

PMID- 8743153
TI  - Lack of effect of cocaine on lysine and alanine uptake in human placental villi
      or transfer in perfused human placenta.
AB  - The effect of cocaine on lysine and alanine uptake in human placental villi and
      transfer across the dually perfused placenta was studied. Uptake (in terms of the
      intracellular to extracellular distribution ratio) of alanine and lysine was 2.81
      +/- 0.30 (n = 5) and 1.45 +/- 0.24 (n = 5) respectively and was unaffected by
      cocaine (50-500 ng mL(-1) in the incubation medium. In the dually perfused
      placenta, the clearance index (ratio of amino acid to antipyrine clearance) was
      0.35 +/- 0.03 and 0.30 +/- 0.05 and the transfer index (ratio of amino acid to L
      glucose clearance) was 2.20 +/- 0.07 and 1.89 +/- 0.29 for lysine and alanine
      respectively. Cocaine at concentrations of 100 ng mL(-1) or 250 ng mL(-1) had no
      effect on the clearance of either amino acid. The results of this study indicate
      that concentrations of cocaine likely to be encountered in vivo do not affect
      uptake of lysine or alanine by placental villi or transfer across the perfused
      placental lobule, in contrast with the report that cocaine reduces uptake of
      alanine by placental vesicles. Experimental models must be critically evaluated
      before accepting the results as pertinent to a clinical situation.

PMID- 8743154
TI  - Transport and metabolism of adenosine in diabetic human placenta.
AB  - Pregnancy complicated by diabetes is a relatively frequent event and may result
      in fetal embriopathy. However, little is known regarding whether placental
      transport functions are altered. In this study, we have compared the activity of
      the nitrobenzylthioinosine (NBMPR)-sensitive adenosine transporter and adenosine
      metabolism in human placental brush-border- and basal-membrane vesicles from
      placentas of normal and diabetic pregnancies. Neither [3H]NBMPR binding, a marker
      of the facilitative-diffusion nucleoside transporter in the human placenta, nor
      adenosine metabolism exhibited a significant difference in either the brush
      border- or the basal-membrane vesicles between the normal and diabetic group,
      except for an increased affinity in [3H]NBMPR binding at the basal side in
      diabetic placenta. This result contrasts with an earlier finding using the same
      group of patients that adenosine transport is downregulated in umbilical vein
      endothelial cells from diabetic pregnancies. It is concluded that adenosine
      transport is modulated selectively in different tissues in diabetic pregnancies.

PMID- 8743155
TI  - Human placental and fetal membrane nitric oxide synthase activity before, during
      and after labour at term.
AB  - The aim of this study was to determine whether any labour-associated changes in
      nitric oxide synthase (NOS) activity occur in human placenta and fetal membranes.
      NOS activity in amnion, choriodecidua, and placenta obtained from women before
      (at Caesarean section, not in labour), during (at Caesarean section, in labour)
      and after (spontaneous onset labour, normal vaginal delivery) labour was assessed
      by measuring conversion of radio-labelled L-arginine to L-citrulline. NOS
      activity, as judged by its inhibition by the specific NOS inhibitor N omega-nitro
      L-arginine, was present in placental and amnionic tissues, but not in
      choriodecidual tissue specimens. Activity detected in choriodecidua was
      significantly blocked during incubation with a high concentration of valine,
      suggesting that L-arginine was being consumed by reactions other than NOS under
      the experimental conditions in that tissue. There were no significant differences
      among the labour groups in either amnion or placental NOS activities measured in
      the presence of 1 microM L-arginine. Amnion NOS activity was significantly less
      than that in placenta. Placental V(max) and Km values (determined after removal
      of endogenous L-arginine) did not differ significantly among the different labour
      groups.

PMID- 8743156
TI  - Parathyroid hormone-related protein (PTHrP) concentrations in human amniotic
      fluid during gestation and at the time of labour.
AB  - To establish the changes associated with gestational age and labour status in
      parathyroid hormone-related protein (PTHrP) concentrations in the amniotic fluid,
      human amniotic fluid was collected from non-labouring and labouring women at < 37
      weeks of gestation (preterm) and at term (> or = 37 weeks). PTHrP was assayed by
      a specific N-terminal radioimmunoassay. PTHrP concentrations in amniotic fluid
      obtained from non-labouring women were significantly lower at preterm (15-36
      weeks; 14.1 +/- 2.5 pmol L(-1); n = 11) than at term (37-42 weeks; 39.3 +/- 7.6
      pmol L(-1); n = 16; P < 0.0009). Concentrations of PTHrP in amniotic fluid
      obtained from labouring women were also significantly lower at preterm (27-36
      week; 12.2 +/- 4.7 pmol L(-1); n = 4; P < 0.01) than at term (37-42 weeks; 63. 8
      +/- 19.6 pmol L(-1); n = 9). There were no significant changes in concentration
      associated with labour status, either at preterm or at term. The physiological
      significance of elevated amniotic fluid concentrations of PTHrP has yet to be
      established, but the data are consistent with the suggestion that PTHrP plays a
      role in fetal membrane function during late gestation.

PMID- 8743157
TI  - Umbilical venous guanosine 3',5'-cyclic phosphate (cGMP) concentration increases
      in asphyxiated newborns.
AB  - Guanosine 3',5'-cyclic phosphate (cGMP) is known to be the second messenger of
      natriuretic peptides and nitric oxide (NO). To investigate the involvement of
      natriuretic peptides in the regulation of the feto-placental circulation,
      specific radioimmunoassays were used to measure the concentrations of atrial
      natriuretic peptide (ANP), brain natriuretic peptide (BNP) and cGMP in the
      umbilical venous plasma of normal and asphyxiated newborns. The plasma
      concentrations of ANP, BNP and cGMP in asphyxiated newborns were 48.3 +/- 12.9
      pm, 24.5 +/- 9.4 pm and 4.4 +/- 1.6 nM (mean +/- s.e.m., n = 10), respectively.
      These values were significantly higher than those in the normal newborns (17.4 +/
      1.9 pm, 4.7 +/- 1.0 pm, and 0.78 +/- 0.14 nM, respectively). Moreover, the
      expression of both ANP-A and ANP-B receptor, biologically active receptors for
      natriuretic peptides, was detected in term human placenta by Northern bolt
      analysis. The expression of natriuretic peptide receptors was further confirmed
      by binding assay using [125I]-labelled ANP and solubilized crude membrane
      preparations of placental tissue. These findings suggest that cGMP is produced in
      the placenta, at least partly, by the action of ANP and BNP secreted from fetal
      heart, in pathophysiological conditions such as fetal hypoxia.

PMID- 8743158
TI  - Human placental cytochrome P450 and quinone reductase enzyme induction in
      relation to maternal smoking.
AB  - Components of cigarette smoke such as cadmium and polycyclic aromatic
      hydrocarbons have been shown to induce quinone reductase (QR) activity in
      placental explants. This study examines the relationship of maternal smoking
      habit and maternal plasma cotinine concentration with the activities in vitro of
      both QR and the cytochrome P450 (CYP1A) marker ethoxyresorufin O-deethylase
      (EROD) in placental tissue. Maternal plasma samples were taken at Week 34 of
      gestation, and placental tissues were obtained at term. Plasma cotinine
      concentrations were determined by high-performance liquid chromatography.
      Trophoblast cytosolic QR and microsomal EROD activities were measured by
      resazurin reduction and ethoxyresorufin O-dealkylation respectively. QR activity
      was inhibited 70% by a mixture of dicoumarol (1 microM) and rutin (20 microM).
      Plasma cotinine concentrations correlated significantly (P < 0.001) with both
      declared smoking rate (r = 0.67, N = 37) and placental EROD activity (r = 0.63, N
      = 36), but not with QR activity, whether measured as total QR activity or
      specifically as either DT-diaphorase or carbonyl reductase. It is concluded that
      smoking up to 40 cigarettes per day induces EROD but does not affect QR activity
      in the placenta at term.

PMID- 8743159
TI  - Placental nitric oxide metabolism.
AB  - There is increasing evidence that nitric oxide (NO) has a role in pregnancy. NO
      is synthesized from L-arginine by NO synthase (NOS), which can exist either as a
      calcium-dependent or a calcium-independent isoform of the enzyme. Both isoforms
      are present in placental villi and the authors have measured NOS activities in
      tissues from early and term normal, pre-eclamptic and growth-retarded
      pregnancies. Higher activities were seen in first trimester placental villi than
      at term. An impairment of NO metabolism occurred in placental villi from pre
      eclamptic and growth-retarded pregnancies. Smoking also results in decreased NOS
      activities in the placental villi, suggesting that problems attributed to smoking
      during pregnancy could be linked to NO metabolism. Polyamines arginine and
      citrulline (all of which are important metabolites in the NO pathway) were also
      measured in placental villous tissues. The data presented in this review article
      are from work carried out in the authors' laboratories and suggest that
      alterations in the placental arginine-NO pathway may not only play a role in the
      physiological changes of advancing gestation but may also contribute to the
      pathophysiology of pre-eclampsia and fetal growth retardation.

PMID- 8743160
TI  - Chorangiosis and chorangioma in three cohorts of placentas from Nepal, Tibet, and
      Japan.
AB  - It has been reported that both chorangiosis and chorangioma are increased in
      placentas at high altitudes. In this study, 1.14% of 2448 Japanese placentas
      obtained at 30-300 m had chorangiosis or chorangioma, compared with 3.24% of the
      Nepalese placentas (1300-3000 m) and 9.09% of the Tibetan samples (3800-4200 m).
      The incidence of both pathologies was significantly higher in the Himalayan
      groups than those of the Japanese group (P < 0.05). Obstetric complications of
      the 28 Japanese placentas with chorangiosis and chorangioma included Caesarean
      section 16 (57.1%), abruptio placentae 2 (7.14%), intrauterine growth retardation
      3 (10.7%), intrauterine fetal death 4 (14.2%) and placenta praevia 4 (14.2%).
      Four infants (14.2%) had Apgar scores ranging from 0 to 3. Among 48 Himalayan
      placentas with chorangiosis and chorangioma, incidence of marked subchorionic
      fibrin was significantly higher (25%) than in the Japanese group (3.57%) (P <
      0.05). The incidence of abnormal insertion of the cord was significantly higher
      (14.2%) in the Japanese group than in the Himalayan group (5%) (P < 0.05). There
      was no significant difference in the frequencies of intervillous thrombosis and
      infarction between the two groups. These findings suggest that the incidence of
      pathological change such as chorangiosis and chorangioma may be increased in
      placentas at Himalayan altitudes.

PMID- 8743161
TI  - Ultrastructure of cellular components of human trophoblasts during early
      pregnancy.
AB  - Two cell types, the cyto- and syncytio-trophoblasts, were identified in human
      chorionic villi of 6-10 weeks' gestation. The intracellular organization of these
      cells was examined. Ultrathin sections of small pieces of chorionic villi
      revealed the presence of a multinucleate syncytiotrophoblastic layer, whose
      surface was covered with microvilli. The cytotrophoblasts, however, had a single
      large nucleus with a prominent nucleolus. An interesting feature of the basement
      membrane of these cells was the presence of aggregates of dark granules in
      samples of the earlier gestational age (6-8 weeks) and granular bodies having a
      dense outer ring and a translucent inner ring with a lucid central area in
      samples of 8-10 weeks' gestation. Both types of granules are mineralized and are
      assumed to perform a buffering role for maintaining the neutrality of the layer.

PMID- 8743162
TI  - Transfer of immunoglobulin G across the isolated perfused human placental lobule.
AB  - This study demonstrates that IgG transfer in vitro across the isolated perfused
      human placental lobule can be successfully studied by using natural forms of IgG.
      The transfer of anti-RhD IgG (anti-D) was measured in the presence and absence of
      intravenous immunoglobulin (IVIgG). When anti-D and IVIgG were present alone each
      crossed the placenta at about the same rate, but when both forms were present at
      the same time the movement of one interfered with the movement of the other. This
      pattern of transfer is consistent with receptor-mediated transcytosis. The
      interactions of IgG with trophoblastic transporters may therefore be studied
      without the complications that might arise from the use of conventionally
      labelled molecules.

PMID- 8743163
TI  - Decidua and placenta in mice after treatment with a synthetic glucocorticoid.
AB  - To investigate a possible long-term effect of glucocorticoids on decidua and
      placenta of mice, a single dose of 24 mg kg-1 body weight triamcinolone acetonide
      in crystalline suspension was given subcutaneously to NMRI mice on gestational
      day (GD) 2. Deciduae and placentae, as well as corticosterone and triamcinolone
      concentrations in maternal plasma of GDs 10 and 17 were examined. NADPH
      cytochrome P450 reductase involved in drug biotransformation was detected
      immunocytochemically and showed co-localization with NADPH diaphorase
      histochemistry in the decidua and placenta. Both reactions were higher in
      endothelial cells of decidual sinusoids on GD 10, but were lower on GD 17 in the
      trophoblast, spongiotrophoblast and extraplacental visceral yolk-sac epithelial
      cells of treated mice than in untreated animals. Histochemistry of 11 beta
      hydroxysteroid dehydrogenase, an enzyme that metabolizes biologically active
      adrenocortical steroids and their synthetic congeners in the placenta, showed
      higher activity on GD 17 in enlarged labyrinthic trophoblast I cells of treated
      mice than in untreated animals. As corticosterone concentrations were still
      decreased on GD 17, when triamcinolone concentrations were no longer detectable,
      a long-term suppression of adrenal gland function seems obvious.

PMID- 8743164
TI  - Vascular responses to sodium nitroprusside in the human fetal-placental
      circulation.
AB  - This study examined the activity of sodium nitroprusside (SNP) in the human fetal
      placental circulation in vitro in pathological and experimental conditions in
      which vascular function may be impaired. SNP (13-3400 nM) caused a concentration
      dependent reduction in fetal arterial perfusion pressure (FAP) in Krebs' perfused
      placental cotyledons, at basal tone and following pre-constriction with
      prostaglandin F2 alpha (PGF2 alpha). SNP-induced reduction in FAP in the PGF2
      alpha pre-constricted fetal-placental circulation was enhanced approximately six
      fold (5.85) in those placentae pre-treated with the nitric oxide (NO) synthase
      inhibitor N omega-nitro-L-arginine (100 microM). Reductions in FAP in the
      preconstricted fetal-placental vasculature caused by SNP were not altered by
      prior infusion of ouabain (100 nM) into the fetal circulation or during low
      oxygen perfusion (O2 tension < 50 mmHg). No differences were observed in the
      responses obtained to SNP in placentae obtained from women with normotensive
      pregnancies or those associated with (i) pregnancy-induced hypertension, (ii)
      intra-uterine growth retardation, or (iii) an elevated umbilical-artery Doppler
      ultrasound systolic/diastolic ratio, in either preconstricted placentae or those
      at basal tone. These findings are consistent with an up-regulation of guanylate
      cyclase/cGMP-mediated vasodilatation in the fetal-placental vasculature following
      complete blockade of endogenous NO production.

PMID- 8743165
TI  - Amniotic fluid composition and fetal and placental growth rates in genetically
      hypertensive and normotensive rats.
AB  - Reduced birth weight has been observed in offspring of the spontaneously
      hypertensive rat (SHR) and in human hypertension. To determine which uterine
      factors might contribute to this fetal underdevelopment, fetal and placental
      growth rates and the volume and composition of amniotic fluid were measured in
      SHR and normotensive control Wistar Kyoto (WKY) rats during the final trimester
      of intra-uterine development. SHR and WKY fetuses were collected on Days 15-22 of
      pregnancy, and fetal and placental weight and amniotic fluid volume were
      recorded. The sodium and potassium concentrations of amniotic fluid were also
      measured. Placental weight was significantly lower in SHR than in WKY between
      Days 15 and 20 of gestation, but significantly higher on Days 21 and 22. Fetal
      weight was significantly lower in SHR between Days 17 and 22. These differences
      were reduced or abolished when fetal and placental weights were corrected for
      differences in maternal weight between strains. Amniotic fluid volume was
      significantly lower in SHR between Days 15 and 18, but significantly higher at
      Days 20, 21 and 22. Amniotic fluid sodium concentration was relatively constant
      over the period of observation and not different between strains. SHR amniotic
      fluid potassium concentration was significantly lower than that of WKY near term.
      Thus, the altered fetal and placental weight of SHR may be due to the overall
      reduced growth rate of this strain. However, the rate of fluid and electrolyte
      resorption close to term is markedly different between strains. The mechanism for
      this altered fluid and electrolyte handling by the SHR feto-placental unit
      remains to be determined.

PMID- 8743166
TI  - Relationship between lupus anticoagulant (LAC) and pregnancy-induced
      hypertension.
AB  - Lupus anticoagulant (LAC), a serum antiphospholipid autoantibody, is believed to
      be one of the causes of infertility or fetal loss. The purpose of the present
      study was to evaluate the role of LAC in the pathogenesis of hypertension during
      pregnancy. In this study, 20 pregnant women with hypertension were classified
      into two groups: 14 patients who did not have hypertension before the pregnancy
      but developed it during the pregnancy (pregnancy-induced hypertension; Group A)
      and 6 patients who had hypertensive or renal disease before the pregnancy, and
      developed further hypertension during the pregnancy (pregnancy-aggravated
      hypertension; Group B). A LAC coagulation assay was performed, and the presence
      of LAC in each group was compared. All 14 patients in group A were LAC-negative.
      In contrast, 3 of the 6 patients in group B were LAC-positive, and had clinical
      autoimmune diseases. The incidence of pregnancy-induced hypertension was also
      examined in 15 pregnancies from 9 LAC-positive women who had a history of
      repeated fetal loss but no systemic autoimmune disease (Group C). None of these
      15 pregnancies had hypertensive complications, even when they reached term. In
      the placentas of LAC-positive women, no characteristic changes other than
      fibrinoid degeneration and microscopic infarction were observed upon histological
      examination. These results suggest that LAC does not relate with the onset of
      hypertension during pregnancy.

PMID- 8743167
TI  - Expression pattern of cytokines in the different compartments of the feto
      maternal unit under various conditions.
AB  - Concentrations of five cytokines, GM-CSF, G-CSF, IL-1, IL-6 and IL-8, were
      determined within five compartments under four different conditions: at the time
      of a Caesarean section performed between 25 and 38 weeks' gestational age in
      normal pregnancy without uterine contraction (n = 12), in normal pregnancy with
      labour already established (n = 8), in pregnancy complicated by amniotic
      infection (n = 11), or under the conditions of preeclampsia with fetal
      intrauterine dystrophy (n = 13), cytokine concentrations were determined in fetal
      arterial and venous blood, in amniotic fluid, and in retroplacentally obtained
      maternal blood and peripheral maternal blood. With dystrophy, the concentrations
      of GM-CSF, G-CSF and IL-1 were about 20-50% lower (P < 0.01) in the amniotic
      fluid, and IL-6 and IL-8 were elevated in maternal peripheral blood (P < 0.01)
      but not within maternal retroplacental blood. Thus, preeclampsia/intrauterine
      dystrophy is characterized by reduction of some cytokines within the amniotic
      fluid compartment and concomitant reactive augmentations of other cytokines
      within the maternal and fetal organism. With amniotic fluid infection,
      concentrations of G-CSF, IL-6 and IL-8 were elevated in all compartments (P <
      0.001) but GM-CSF and IL-1 showed a significant rise only within amniotic fluid
      and retroplacental maternal blood (P < 0.001), a rise that was apparently not
      transmitted to peripheral maternal or fetal blood. Care was taken to exclude the
      presence of uterine contractions in the group of controls, because this condition
      by itself causes severe elevation of cytokine concentrations, which are
      pronounced within amniotic fluid.

PMID- 8743168
TI  - Effect of asymmetric dimethyl arginine on nitric oxide synthase activity in
      normal and pre-eclamptic placentae.
AB  - An endogenous inhibitor of nitric oxide synthase (NOS), NG,NG dimethylarginine
      (asymmetric dimethylarginine, ADMA), which is present in human plasma and urine,
      has been reported to be elevated in the plasma of women with pre-eclampsia. As
      ADMA inhibition may contribute to reduced placental NOS activity observed in pre
      eclampsia, the aim of this study was to compare the effects of ADMA on placental
      NOS activity from pre-eclamptic and normal pregnancies (gestational ages 38.4 +/-
      0.9 and 38.3 +/- 0.3 weeks respectively). NOS activity was determined by
      measuring the conversion of [3H]L-arginine to [3H]L-citrulline in homogenates of
      normal and pre-eclamptic placentae in the absence and presence of increasing
      concentrations of ADMA (1-100 microM). The IC50 for ADMA for the pre-eclamptic
      placentae (22.1 +/- 2.1 microM, n = 6) was not significantly different from that
      for the normal placentae (18.8 +/- 1.4 microM, n = 6). When ADMA and L-arginine
      in homogenates was removed by ion exchange chromatography and exogenous L
      arginine replaced (32 microM), the IC50 for the pre-eclamptic placentae (19.5 +/-
      1.8 microM, n = 6) was not significantly different than that for the normal
      placentae (20.9 +/- 1.0 microM, n = 6), and NOS activity in the absence of
      endogenous and exogenous ADMA was still reduced in pre-eclamptic placentae. These
      results provide no evidence that the sensitivity of placental NOS to ADMA is
      affected by pre-eclampsia, or that placental ADMA contributes to the reduction of
      placental NOS in pre-eclampsia.

PMID- 8743169
TI  - Endothelin receptors in the human amnion, chorion laeve, decidua vera and
      placenta.
AB  - The levels of endothelin-1 (ET-1) and the characteristics of endothelin (ET)
      receptors were investigated in the amnion, chorion laeve, decidua vera and
      placenta by using a specific radioimmunoassay for ET-1 and a saturation binding
      assay for ET. ET receptor gene expression in these tissues was also examined by
      Northern blot analysis. The levels of ET-1-like immunoreactivity (ET-1-LI) in the
      human amnion, chorion laeve, decidua vera and placenta obtained at elective
      Caesarean section before labour onset at term (mean +/- s.e.m.) were 1260 +/- 380
      (n = 6), 3740 +/- 980 (n = 4), 4550 +/- 780 (n = 4) and 2450 +/- 470 (n = 4) pg g
      1 wet weight, respectively. The levels of ET-1-LI in the tissues obtained after
      spontaneous vaginal deliveries at term did not differ from these. Gel-permeation
      chromatography and reverse-phase high-performance liquid chromatography revealed
      that the ET-1-LI in these tissues was mainly composed of ET-1. Scatchard analysis
      of the saturation binding assay for [125I]-labelled ET-1 and [125I]-labelled ET-3
      indicated that high concentrations of both ET-A and ET-B subtypes of receptor
      were present in membrane fractions from the chorion laeve, decidua vera and
      placenta. However, in membrane fractions from the amnion, no ET receptors could
      be detected. These results were confirmed by Northern blot analysis using human
      ET-A and ET-B receptor cDNA probes. Taken together, these results suggest that
      the amnion is not the site of action of amniotic ET, and that ET may be involved
      in the regulation of functions of the chorion laeve or decidua vera.

PMID- 8743170
TI  - Activation of phospholipase D in cultured human amnion cells.
AB  - The regulation of phospholipase D (PLD) activity in the human amniotic membrane
      was examined using primary cultures of amnion cells. Cultured amnion cells were
      labelled with [3H]oleic acid, and PLD activity was determined as the amount of
      [3H]phosphatidylethanol (PEt) produced during incubation in the presence of 0.1%
      ethanol. PLD activity in cultured amnion cells was activated by addition of
      arginine vasopressin and oxytocin. PLD activity was also stimulated by treatment
      was arachidonic acid, the product of phospholipase A2 (PLA2), and phospholipase C
      (PLC). These results indicate that PLD in amnion cells is activated by substances
      present in amniotic fluid, and that cross-talk between phospholipases A2, C and D
      may occur in amnion cells.

PMID- 8743171
TI  - Effect of maternal glucocorticoid treatment on ovine fetal fluids at 0.6
      gestation.
AB  - This study examined the effects of maternal dexamethasone treatment on the volume
      and composition of fetal fluids, and on placental morphology at 0.6 gestation (80
      90 days). Nine pregnant ewes were infused with dexamethasone (D, 0.76 mg h-1 for
      72 h) while an additional nine ewes received saline (S, 0.38 mL h-1 for 72 h).
      Allantoic fluid (ALF) volume was significantly greater (P < 0.01) in the D group
      (737 +/- 116 mL) than in the S group (190 +/- 55 mL), but there was no difference
      in amniotic fluid (AMF) volume. The urine flow rate was 11 times higher in three
      D fetuses. The 51Cr-EDTA infused into the bladders of four fetuses during the
      final 4-5 h of the 72 infusions was detected in both AMF and ALF. Dexamethasone
      treatment significantly altered the composition of the fetal fluids but had no
      affect on fetal body weight, organ weights and placental weight; however, there
      were fewer cotyledons under 5 g (P < 0.05). In the D group, 3% of cotyledons were
      of the 'bovine' type in morphology, whereas all cotyledons in the S group were of
      the 'ovine' type. These findings suggest that prolonged exposure to large doses
      of glucocorticoids during pregnancy would affect the volume and composition of
      the fetal fluids and placental morphology, with potentially detrimental effects
      on the fetus.

PMID- 8743172
TI  - Elevated fibrinopeptide A and B levels during thrombolytic therapy: real or
      artefactual?
AB  - There is good evidence that thrombolytic therapy induces a procoagulant state
      that retards the lytic process and triggers reocclusion. Thus, both in
      experimental animal systems and in humans, potent inhibitors of platelets and
      antithrombin III-independent thrombin inhibitors have been shown to be better
      than heparin at accelerating thrombolysis and preventing reocclusion. These in
      vivo observations have lent credence to the concept that elevated FPA levels that
      are suppressed by heparin reflect systemic activation of coagulation during the
      thrombolytic process. However, this concept may not be correct. Thus, when
      heparin is given in conjunction with plasminogen activators only modest increases
      in FPA levels are found, and our data suggest that this is due, at least in part,
      to the activity of enzymes other than thrombin. In the absence of concomitant
      heparin, thrombolytic therapy causes a much greater increase in the FPA values.
      These high FPA values are rapidly reduced by heparin, even though heparin has
      limited antithrombotic activity in the setting of pharmacologic thrombolysis.
      Based on these considerations, we believe that plasma FPA and desarginine FPB
      levels should not be used as specific markers of thrombin activity during the
      course of thrombolytic therapy and suppression of elevated FPA values by heparin
      should not be accepted as evidence that heparin is effective in this clinical
      setting.

PMID- 8743173
TI  - The pathogenesis of the antiphospholipid syndrome: a hypothesis based on
      parallelisms with heparin-induced thrombocytopenia.

PMID- 8743174
TI  - Increased cyclin dependent kinase in aortic tissue of rats fed homocysteine.
AB  - BACKGROUND: Hyperhomocyst(e)inemia is strongly associated with occlusive arterial
      disease. Several mechanisms for the development of vascular lesions have been
      described. A direct effect of homocysteine on proliferation of smooth muscle
      cells and collagen expression was proposed recently. These observations led us to
      examine the effect of homocysteine on cyclin dependent kinase, the starter of
      mitosis and reflecting proliferation. METHODS AND RESULTS: Thirty Him: OFA rats
      were divided into three groups. Ten animals were fed for a period of six weeks 50
      mg/kg body wt per day homocysteine, ten the same dose of homocysteic acid and ten
      remained untreated controls. At the end of the experiment we determined aortic
      cyclin dependent kinase, phosphokinases A and C, aortic homocyst(e)ine and aortic
      hydroxyproline. Aortic cyclin dependent kinase was significantly (p = 0.0001)
      elevated in the homocysteine treated group (mean 120 +/- 15) compared with the
      homocysteic acid treated group (mean 71 +/- 11) or the untreated group (mean 72
      +/- 10 fmol/mg aortic tissue). Aortic homocyst(e)ine was significantly higher in
      homocysteine treated animals (p = 0.0002) strongly correlating with cyclin
      dependent kinase (r squared = 0.85, p = 0.0001) and with aortic hydroxyproline (r
      squared = 0.66, p = 0.0001), which in turn was significantly (p = 0.0001)
      increased in the homocysteine treated group. Phosphokinases A and C determined to
      rule out nonspecific effects on kinases were not increased by administered
      homocysteine. CONCLUSIONS: Our findings indicate that homocysteine stimulates
      aortic cyclin dependent kinase with the possible consequence of proliferation of
      aortic cells. Aortic collagen accumulation could be explained by either the
      homocysteine-effect on collagen synthesis described in literature, or
      secondarily, by increased proliferation of collagen produced aortic cells.

PMID- 8743175
TI  - Mutation spectrum in patients with Wiskott-Aldrich syndrome and X-linked
      thrombocytopenia: identification of twelve different mutations in the WASP gene.
AB  - Twelve different mutations in the WASP gene were found in twelve unrelated
      families with Wiskott-Aldrich syndrome (WAS) or X-linked thrombocytopenia (XLT).
      Four frameshift, one splice, one nonsense mutation, and one 18-base-pair deletion
      were detected in seven patients with WAS. Only missense mutations were found in
      five patients diagnosed as having XLT. One of the nucleotide substitutions in
      exon 2 (codon 86) results in an Arg to Cys replacement. Two other nucleotide
      substitutions in this codon, R86L and R86H, have been reported previously, both
      giving rise to typical WAS symptoms, indicating a mutational hot spot in this
      codon. The finding of mutations in the WASP gene in both WAS and XLT gives
      further evidence of these syndromes being allelic. The relatively small size of
      the WASP gene facilitates the detection of mutations and a reliable diagnosis of
      both carriers and affected fetuses in families with WAS or XLT.

PMID- 8743176
TI  - Evaluation of a soluble fibrin assay in patients with suspected pulmonary
      embolism.
AB  - In order to determine the clinical utility of an enzyme immunoassay (EIA) for
      soluble fibrin in patients with suspected pulmonary embolism (PE), 195 unselected
      patients with suspected PE underwent blood sampling for measurement of plasma
      levels of soluble fibrin, and objective testing for PE. A soluble fibrin result
      of < or = 0.75 micrograms/ml showed a sensitivity of 100% for PE and a
      specificity of 12.8%, whereas a soluble fibrin result of < or = 1.35
      micrograms/ml showed a sensitivity of 90.3% and a specificity of 49.4% for PE.
      The soluble fibrin assay has potential clinical utility in excluding PE.

PMID- 8743177
TI  - Inhibition of protein S by autoantibodies in patients with acquired protein S
      deficiency.
AB  - This study was undertaken to analyze antibodies to protein S (PS) in patients
      with an acquired PS deficiency. Plasma from symptomatic patients with acquired (n
      = 14) or congenital (n = 10) PS deficiency and 10 healthy donors was screened for
      PS antibodies by immunoblotting and for anti-phospholipid antibodies. PS
      antibodies (IgG) were detected in five of the patients with acquired PS
      deficiency. These antibodies belonged to the G1 and G4 immunoglobulin subclasses.
      IgG fractions from the same 5 patients were shown to inhibit PS activity. The
      inhibition of PS activity by the 5 IgG fractions was shown to be time- and dose
      dependent and was abolished following incubation with purified PS, while no
      effect was found after absorption with cardiolipin micelles. In addition,
      anticardiolipin monoclonal or human purified antibodies, failed to exert
      significant PS inhibition. These findings demonstrate that anti-PS antibodies are
      able to inhibit PS activity and that this is independent of anti-phospholipid
      antibodies. Given the clinical features of the patients, these antibodies should
      be regarded as an expression of the broad autoimmune syndrome involving the
      phospholipid-binding plasma proteins.

PMID- 8743178
TI  - Platelet density and size in inflammatory bowel disease.
AB  - OBJECTIVE: The present study investigates platelet density and mean platelet
      volume (MPV) in active inflammatory bowel disease (IBD). EXPERIMENTAL PROTOCOL:
      27 patients with IBD (18 ulcerative colitis and 9 Crohn's disease) were compared
      to 12 healthy volunteers. 18 subjects had active disease. Platelet counts and
      mean platelet volume (MPV) were determined. Thereafter, platelets were separated
      according to density on a linear preformed Percoll gradient. A computerized
      device was employed for scanning transmission variations and thus the platelet
      distribution in the gradient and the platelet peak were identified. RESULTS AND
      CONCLUSIONS: Subjects with active IBD had greater platelet density (p = 0.02) and
      lower MPVs (p < 0.001). These findings may indicate augmented platelet granule
      content. The study also demonstrates that a low MPV is associated with active
      IBD.

PMID- 8743179
TI  - Anticoagulant response to Agkistrodon contortrix venom (ACV test): a new global
      test to screen for defects in the anticoagulant protein C pathway.
AB  - As specific assays used to identify defects in the protein C (PC) anticoagulant
      pathway are laborious and expensive, we describe here a global test to screen for
      these defects. This assay is expressed as the ratio of two activated partial
      thromboplastin times, one in the absence and one in the presence of 0,125 U/ml of
      the PC activator of Agkistrodon contortrix venom (ACV). Eight of the 168 healthy
      volunteers of the control group exhibited an ACV ratio below the lower normal
      limit of 3.37 [6 subjects with the mutation Arg 506 to Gln in their factor V gene
      (FV R506Q) and one with PS deficiency]. 128 patients who have had at least one
      episode of deep-vein thrombosis were retrospectively studied. All patients
      carrying FV Q506R (n = 48), PC deficiency (n = 14) or combined defects, i.e. FV
      Q506R and PC deficiency (n = 4) or FV Q506R and PS deficiency (n = 3), had ACV
      ratios < 3.37. PS deficient plasmas (n = 20) exhibited ACV ratios which
      overlapped normal range. ACV ratios of one out of seven patients with
      antithrombin deficiency, and 10% of patients without identified defect in the PC
      anticoagulant pathway (n = 30) were < 3.37. An ACV ratio raised to 3.70 could
      lead to a test identifying all patients with a defect in the PC anticoagulant
      pathway.

PMID- 8743180
TI  - Low plasma levels of factor VIIc and antigen are more strongly associated with
      the 10 base pair promoter (-323) insertion than the glutamine 353 variant.
AB  - In a group of 705 healthy middle-aged men, we have examined the relationship
      between plasma levels of Factor VII (FVII) c and Factor VII antigen (FVIIag) and
      two polymorphisms in the FVII gene. One polymorphism alters arginine at position
      353 to glutamine (R/Q), and the other is the result of a 10 base pair (bp)
      insertion in the promoter region at position -323 from the start of translation
      (0/10bp). The frequency for the Q allele was 0.105 (95% CI 0.09-0.12) and for the
      10bp allele was 0.117 (95% CI 0.10-0.13). Men who were carriers of either of the
      rare alleles had levels of FVIIc and FVIIag that were approximately 20% lower
      than non-carriers, and both of these effects were highly statistically
      significant (p < 0.0001). Strong allelic association was observed between the two
      polymorphisms, with R and 0 bp being on the same chromosome in 96% of cases, and
      Q and 10 bp being on the same chromosome in 90% of cases where this could be
      determined unambiguously (Delta = 0.92, chi 2 = 1206, p < 0.0001). This strong
      allelic association created three major genotype groups which were found to have
      significantly different levels of FVIIc (p < 0.001). In the 547 men homozygous
      for both common alleles (R/R & 0/0), mean (SD) FVIIc was 101 (29) as compared
      with 85 (30) in the 20 men with the genotype R/R & 0/10 and 81 (23) in the 126
      men with the genotype R/Q & 0/10, suggesting a larger lowering effect associated
      with the 10 bp allele (16%) compared to the Q allele (an additional 4%). The
      lowering effect on FVII associated with the 10 bp allele remained statistically
      significant after adjusting for the effect of the Q allele (p = 0.004 for FVIIc
      and p = 0.06 for FVIIag), but the effect associated with the Q allele was no
      longer significant after adjusting for the 10 bp allele, suggesting that the
      strongest effect on levels of FVIIc was associated with the 0/10 bp genotype. In
      the sample overall, plasma FVIIc was associated positively with serum
      triglyceride concentration and the slope of this relationship was significantly
      greater in those with the genotype R/R compared to the other groups combined
      (0.12 versus 0.02, p = 0.008) with differences of similar size seen in the 0/0
      compared to 0/10 + 10/10 groups. However, using the combined genotype, the slope
      of this relationship in the R/R & 0/10 group was 0.38 and was significantly
      steeper (p = 0.01) than in the other two groups who did not differ in this
      respect (slopes 0.11 and 0.08). This effect was seen on four subsequent annual
      examinations, and was also evident in the relationship between FVIIag and
      triglyceride concentration (p = 0.003 for difference between groups measured at
      baseline only). These data suggest that part of the previously described effects
      on FVIIc levels associated with the R/Q polymorphism may be explained by genetic
      variation in the promoter region of the FVII gene.

PMID- 8743181
TI  - Purification, characterization and cDNA cloning of a novel anticoagulant of the
      intrinsic pathway, (prolixin-S) from salivary glands of the blood sucking bug,
      Rhodnius prolixus.
AB  - The salivary glands of the blood sucking insect, Rhodnius prolixus, have an
      anticoagulant, prolixin-S, which was reported as a specific inhibitor of
      intrinsic coagulant pathway. Prolixin-S was purified from the salivary glands
      extract of Rhodnius prolixus by gel filtration and anion exchange HPLC by
      assaying prolongation of activated partial thromboplastin time (APTT). The
      isolated protein specifically inhibited factor IXa-catalyzed activation of factor
      X in the presence of Ca2+ and phospholipids irrespective of the presence or
      absence of factor VIIIa. The anticoagulant factor had red color and a specific
      absorbance peak at 402 nm and thus it was identified as a heme protein. A
      Rhodnius prolixus salivary gland cDNA library was prepared, screened with an
      antibody against prolixin-S and its complete cDNA sequence was determined. cDNA
      and deduced amino acid sequences showed that prolixin-S is a novel anticoagulant
      of 19,922 Da, which has no sequence homology with any other anticoagulant
      reported so far.

PMID- 8743182
TI  - Infusion of phospholipid vesicles amplifies the local thrombotic response to TNF
      and anti-protein C into a consumptive response.
AB  - Inflammation often is considered a contributing factor to both thrombosis and
      disseminated intravascular coagulation. The molecular mechanisms that dictate
      which of these clinical manifestations will result from the inflammatory stimulus
      remain obscure. Bacterial infection and certain tumors are common initiators of
      the disseminated intravascular coagulant response. Complement activation
      resulting from bacterial infection shares with selected tumors the capacity to
      generate or release membrane particles that lack functional adhesion receptors
      and hence could circulate to amplify a disseminated intravascular coagulant
      response. We developed a model of venous thrombosis that resulted in localized
      thrombus formation without disseminated intravascular coagulation. The model
      involves infusion of tumor necrosis factor, blockade of protein C and a partial
      decrease in venous flow caused by ligation of the superficial femoral vein
      without obstruction of the deep formal vein. Infusion of phospholipid vesicles
      into this model resulted in amplification of a localized thrombotic response into
      a consumptive response. Seven different groups of animals were studied. The first
      three groups established the conditions necessary to produce deep vein
      thrombosis. The second four groups established the conditions necessary to
      produce disseminated intravascular coagulation. The infusion of phospholipid
      vesicles plus tumor necrosis factor and anti-protein C antibody resulted in
      consumption of fibrinogen, the production of thrombin/antithrombin complexes, a
      fall in platelet count, and venous thrombosis. Without ligation and
      catheterization phospholipid vesicles failed to produce the consumptive response.
      We conclude, therefore, that phospholipid vesicles can amplify a local thrombotic
      response into a consumptive response, and that vesiculation accompanying
      inflammation is one means by which localized coagulant activity may be amplified
      to produce disseminated intravascular coagulation.

PMID- 8743183
TI  - Experimental haemorrhagic effect of two-domain non-glycosylated tissue factor
      pathway inhibitor compared to low molecular weight heparin.
AB  - The glycosylated multivalent three-domain Kunitz inhibitor TFPI is a natural
      inhibitor of tissue factor-FVIIa complex in the presence of FXa. TFPI has an
      experimental antithrombotic capacity indistinguishable from LMWH in a
      prophylactic dose, regardless of glycosylation and of the third domain. An
      inherited equilibrium between antithrombosis and haemorrhage exists. The aim of
      the study was to evaluate whether a two-domain non-glycosylated TFPI (117QTFPI1
      161) has a bleeding potential in a rat gastric mucosa model. Groups; placebo,
      LMWH (tinzaparin) 60 and 250 anti-Xa IU/kg and 117 QTFPI1-161 1.0 and 10.0 mg/kg,
      given i.v. (bolus injection), randomised double dummy design. All actively
      treated groups significantly prolonged both the bleeding volume (493-984
      microliters) and the bleeding time (10-20 min) compared to placebo (41
      microliters, 2 min). It was not possible to distinguish a difference between the
      lower dose of LMWH and 117QTFPI1-161 in either parameter (p = 0.23-0.71). The two
      doses of 117QTFPI1-161 caused elevation of plasma-TFPI, 18 and 150 times baseline
      value. Both LMWH doses (0.6-3.2 anti-Xa IU/ml) and both 117QTFPI1-161 doses (0.2
      2.7 anti-Xa IU/ml), caused significant effect in the anti-Xa assay, however
      117QTFPI1-161 significantly less. Only the largest dose of 117QTFPI1-161 caused
      significant prolongation in the APTT assay (34 s). Both doses of LMWH caused
      significant prolongation (60-300 s). LMWH was the only substance to prolong the
      dilute-PT assay. Non-glycosylated two-domain 1.0 mg/kg TFPI, yielding
      supraphysiological plasma concentration, has an experimental haemorrhagic
      potential indistinguishable from LMWH in a prophylactic dose. The effect mediated
      by this type of TFPI could primarily be due to an inhibition of FXa.

PMID- 8743184
TI  - Prothrombin time sensitivity and specificity to mild clotting factor deficiencies
      of the extrinsic pathway: evaluation of eight commercial thromboplastins.
AB  - Prothrombin-time (PT) sensitivity and specificity to mild clotting factor II, V,
      VII and X deficiencies have rarely been studied. We therefore carried out a
      prospective study, in 350 patients, of eight commercial thromboplastins (CTs) in
      their ability to detect mild clotting factor deficiencies, notably in factor VII.
      In each patient the factor II, V, VII and X clotting activities and PT performed
      with each CT were determined. For each CT, PT sensitivity and specificity in
      detecting factor deficiencies below 0.5 U/ml or below 0.4 U/ml were determined at
      various PTs, and then Receiver Operator Characteristic curves constructed. At
      optimum PT threshold level (sensitivity = specificity), exactitude varied from
      0.64 to 0.74 (p < 0.01) and from 0.67 to 0.81 (p < 0.0001) in detecting
      deficiencies below 0.5 and 0.4 U/ml respectively. In conclusion, this study shows
      the limits of the PT test as performed with 8 CTs in patients with mild clotting
      factor deficiencies. The impact of such differences in sensitivity and
      specificity on monitoring certain patients subjects to decrease in coagulation
      factor, and, in particular, of those under low dose oral anticoagulant, remains
      to be determined.

PMID- 8743185
TI  - Monoclonal antibodies to human fibrin: interaction with other animal fibrins.
AB  - Four monoclonal antibodies have previously been raised in our laboratory for
      possible use in thrombus imaging and the targeting of thrombolytic agents. These
      antibodies were raised to various human fibrin-related immunogens and each
      antibody had been selected for its specificity towards fibrin and not fibrinogen.
      To study further these antibodies in animal circulation models both in vivo and
      in vitro, their selectivity towards human fibrin as opposed to other animal
      fibrins was examined. In this study dissociation constants for each antibody with
      each of six species fibrins (human, baboon, pig, dog, sheep and rabbit) were
      estimated using both fibrin clots and monolayers. Some limited data were also
      obtained with Sepharose-fibrin. Of the antibodies two (denoted 12B3B10 and
      12B3A11) are seen to bind almost exclusively to human fibrin with dissociation
      constants of about 8 x 10(-10) M using fibrin clots and monolayers. These same
      two mabs bound to baboon fibrin with a dissociation constant of 2 x 10(-9) M,
      while neither displayed significant levels of binding to the fibrins from dog,
      pig, sheep and rabbit. The other two antibodies investigated (1H10 and 5F3) were
      found to bind well to fibrins of human, baboon, pig and dog, with dissociation
      constants in the range of 1.4-4.2 x 10(-9) M. However neither 1H10 nor 5F3
      displayed significant recognition of sheep and rabbit fibrins. Both 1H10 and 5F3
      were also found by means of competitive ELISA's to retain their selectivity to
      baboon, dog and pig fibrins in the presence of their respective fibrinogens.

PMID- 8743186
TI  - Increased expression of plasminogen activator inhibitor-1 in R. rickettsii
      infected endothelial cells.
AB  - Changes in PAI-1 expression in human umbilical vein endothelial cells (HUVEC)
      were studied following in vitro infection with Rickettsia rickettsii. A 1.8-fold
      increase in secreted PAI-1 activity occurred in infected versus control cultures
      (p = 0.03) at 24 h but not at earlier timepoints. A similar increase (1.4-fold)
      in secreted PAI-1 antigen (p < 0.005) was measured by ELISA. To determine whether
      this increase was due to increased synthesis of PAI-1, HUVEC were metabolically
      labeled with 35S-methionine concurrent with R. rickettsii infection. Such
      infection resulted in a 1.9-fold increase in labeled PAI-1 in the medium at 24 h
      (p = 0.036). Increase steady-state levels of PAI-1 mRNA were detected as early as
      18 h by Northern blot analysis, peaking (5.5-fold) at approximately 24 h. These
      results indicate that PAI-1 production is increased in RR-infected endothelial
      cells, an effect that may contribute to the vascular occlusions noted in Rocky
      Mountain spotted fever.

PMID- 8743187
TI  - The significance of hypofibrinolysis for the risk of recurrence of venous
      thromboembolism. Duration of Anticoagulation (DURAC) Trial Study Group.
AB  - An impaired fibrinolytic function has been described in several case-control
      studies of patients with venous thromboembolism (VTE). In the present study the
      correlations between some fibrinolytic compounds and future recurrent VTE were
      investigated. Blood samples for analysis of tissue-type plasminogen activator (t
      PA) antigen before and after 10 min of venous occlusion (V.O.) and plasminogen
      activator inhibitor type 1 (PAI-1) activity were taken at 6 months after the
      first episode of VTE or the first recurrent VTE in 784 and 207 patients,
      respectively, who were anticoagulated for 1.5 or 6 months (first VTE) and 6
      months or indefinitely (first recurrence). During a follow-up of 3-6 years from
      the event which qualified for inclusion there have been 177 recurrences. All
      initial and recurrent events were verified with objective diagnostic methods.
      Using cut off points of 10.0 ng/ml for t-PA antigen before V.O. and 30 AU/ml for
      PAI-1 in samples taken at rest, there were more patients above those levels in
      the groups with than without further recurrence (t-PA antigen, 50% versus 36%, p
      = 0.001; PAI-1, 18% versus 12%, p = 0.045). In the 495 patients, who received
      oral anticoagulation for 6 months, t-PA antigen at rest discriminated better,
      with 59% versus 34% of patients above 10 ng/ml in the groups with and without
      recurrence, respectively (p < 0.001). The t-PA antigen levels after V.O. and the
      fibrinolytic capacity (t-PA antigen after V.O. minus t-PA antigen before V.O.)
      were distributed similarly in patients with and without new recurrences. There
      was a statistically significant positive correlation between age and t-PA antigen
      (p < 0.001), and by analysis of covariance the difference between the groups with
      and without further recurrence regarding t-PA antigen disappeared. In conclusion,
      increased levels of PAI-1 and t-PA antigen in VTE-patients correlate with
      development of recurrent VTE within the next 3-6 years, but the value of these
      components in predicting future events for the individual patients is limited.

PMID- 8743188
TI  - Influence of maximal ergometric exercise on endothelin concentrations in relation
      to molecular markers of the hemostatic system.
AB  - The effects of moderate 30 min cycle ergometer exercise (aerobic metabolism; 0.85
      3.71 mmol.1(-1) lactate) followed by short-term exercise at maximal capacity
      (anaerobic metabolism; 5.09 to 17.75 mmol.1(-1) lactate) on endothelin (ET) and
      hemostatic variables (tissue plasminogen activator [t-PA] antigen, prothrombin
      fragments [F1,2], thrombin-antithrombin III complex [TAT], prothrombin time and
      partial thromboplastin time) were investigated in 15 male healthy subjects of
      varying fitness levels. Endothelin was measured twice before and immediately
      after maximal cycle exercise. The results show an increase in endothelin
      concentration [10.0 pg.ml-1 (baseline) + 6.1 pg.ml-1 (increase post exercise)].
      ET did not increase under control conditions. Moderate 30 min exercise caused an
      increase in t-PA antigen concentration (3.66 + 3.15 ng.ml-1) and short-term
      maximal exercise produced a markedly higher elevation in this variable (+10.6
      ng.ml-1). F1,2 increased (810 + 40 pmol.l-1) under moderate and by 150 pmol.l-1
      under anaerobic exercise. TAT increased only at maximal exercise levels (1.01 +
      0.32 ng.l-1). No changes were found in any of these variables under control
      conditions. No correlation of endothelin and the hemostatic variables was found.
      It is concluded that endothelin and hemostatic markers increase independently
      during moderate and maximal exercise.

PMID- 8743189
TI  - Accumulation of unphosphorylated calponin in the submembranous cytoskeletons of
      arachidonic acid-stimulated human platelets.
AB  - Calponin, a basic smooth-muscle protein capable of binding to F-actin,
      tropomyosin and calmodulin in vitro, was tested for its expression and
      subcellular localization in resting and stimulated human platelets. Using
      immunoblotting techniques calponin was revealed as a single protein band with a
      molecular weight of 34 kDa. Although calponin has been shown to be
      proteolytically degraded by calpain, in the presence of the calpain inhibitor E
      64 and EGTA a significant hydrolysis of calponin could not be detected. Upon
      stimulation with 10 microM arachidonic acid calponin became increasingly
      incorporated into Triton X-100 insoluble cytoskeletal fractions reaching a
      plateau after 15 s. The accumulation of calponin in the cytoskeletons of
      stimulated platelets paralleled the polymerization of actin into newly formed
      microfilaments. Immunofluorescence microscopy revealed a submembranous co
      localization of calponin and actin in aggregated platelets. Since isolated
      calponin is phosphorylated by protein kinase C and Ca2+/calmodulin-dependent
      protein kinase II thereby losing its inhibitory effect on the actomyosin MgATPase
      activity, we examined whether changes in cell shape due to platelet stimulation
      are accompanied by a phosphorylation of calponin. By performing immunoblotting
      analysis on either resting or stimulated platelets phosphorylation of calponin on
      tyrosine, serine or threonine residues could not be demonstrated. In line,
      [32P]radiolabeling experiments were unable to detect phosphate incorporation into
      calponin. These observations support the hypothesis that calponin plays a
      physiological role in regulating contraction and secretion of human platelets
      even in the absence of its phosphorylation.

PMID- 8743190
TI  - The lysosomal granule membrane protein, LAMP-2, is also present in platelet dense
      granule membranes.
AB  - Lysosomal Associated Membrane Protein-2 (LAMP-2) is an inherent component of
      lysosomal granule membranes in diverse cell types, including platelets. We
      examined platelets for evidence of LAMP-2 in dense granule membranes as CD63 has
      previously been shown to be present in both lysosomal and dense granule
      membranes. Immunological techniques were used to examine the localization of LAMP
      2 in control platelets and those from an individual with Hermansky-Pudlak
      syndrome (HPS), a condition characterised by platelet dense granule deficiency.
      Immunoblotting studies demonstrated that LAMP-2 was enriched in a dense granule
      preparation. Flow cytometry of thrombin-stimulated control platelets was
      consistent with biphasic surface expression of LAMP-2. The early expression was
      accompanied by dense granule, but minimal lysosomal granule, release. The late
      expression was accompanied by additional lysosomal granule release only. Thrombin
      stimulation of HPS platelets showed only late, lysosome-associated LAMP-2
      expression. Immunoelectron microscopy indicated the presence of LAMP-2 in the
      membranes of serotonin-containing granules as identified by an anti-serotonin
      polyclonal antibody. These data indicate that LAMP-2 is present in the membranes
      of platelet dense granules in addition to lysosomal granules, and has a similar
      distribution to CD63.

PMID- 8743191
TI  - Platelet aggregation and adhesion during dietary copper deficiency in rats.
AB  - The role of dietary copper deficiency in platelet-to-endothelial cell adhesion
      and in platelet-to-platelet aggregation was studied in vitro. Platelets were
      obtained from male, weanling Sprague-Dawley rats fed purified diets which were
      either copper-adequate (CuA, 6.3 micrograms copper/g of diet) or copper-deficient
      (CuD, 0.3 microgram/g of diet) for 4 weeks. The platelet adhesion study was
      performed by adding CuA or CuD platelets either suspended in homologous plasma or
      in Tyrode buffer salt solution (TBSS) to cultured rate endothelial cells. After a
      one hour incubation at 37 degrees C non-adhered platelets were removed and
      counted in a microcytometer. Platelet aggregation in platelet rich plasma (PRP)
      samples was induced by adding ADP (2 x 10(-4)M) and measured in a turbidometric
      aggregometer. The content of von Willebrand factor (vWF) in platelets and in
      plasma and the content of fibrinogen in platelets was determined. Platelet
      adhesion to rat endothelial cells was significantly lower for platelets from CuD
      rats than for platelets from CuA rats. ADP induced platelet aggregation from CuD
      rats was significantly higher than platelet aggregation from CuA rats. The
      content of vWF in platelets and in plasma from CuD rats was significantly lower
      than in platelets and plasma from CuA rats. However, the amount of fibrinogen in
      platelets from ++CuD rats was about 4-fold higher than that in platelets from CuA
      rats while the plasma fibrinogen was lower in CuD rats than in CuA rats. These
      studies illustrate that copper deficiency diminishes platelet adhesion to
      endothelial cells but increases platelet aggregability. The results suggest that
      these physiological alterations may be the result of decreased platelet vWF and
      increased platelet fibrinogen during dietary copper deficiency.

PMID- 8743192
TI  - High density lipoproteins enhance the Na+/H+ antiport in human platelets.
AB  - In the present study, we investigated the effect of high density lipoproteins 3
      (HDL3) on Na+/H+ exchanger activity and cytosolic pH (pHi) in human platelets.
      HDL3 alone failed to affect pHi, but preincubation with HDL3 significantly
      enhanced the Na+/H+ antiport activation brought about by acidification with 100
      mM sodium propionate or stimulation with 0.05 U/ml thrombin. the stimulatory
      effect of HDL3 was unaffected by indomethacin excluding a role for cyclooxygenase
      products. The HDL3 effect was not mediated by Ca2+/calmodulin-dependent protein
      kinase as HDL3 failed to increase cytosolic free calcium concentration. However,
      the potentiating effect of HDL3 was completely blocked in the presence of the
      protein kinase C inhibitor, bisindoylmaleimide and the phosphatidylcholine
      specific phospholipase C inhibitor, D609. Furthermore, the effect of HDL3 was
      abolished after covalent modification of HDL3 with dimethylsuberimidate and was
      not observed in platelets from Glanzmann thrombasthenia type 1 which do not
      express GP IIb/IIIa, as well as in platelets preincubated with anti-GP IIb/IIIa
      polyclonal antibodies. We conclude that HDL3 enhances the sodium propionate- and
      thrombin-induced Na+/H+ antiport activity in human platelets via binding to GP
      IIb/IIIa and activation of protein kinase C and phosphatidylcholine-specific
      phospholipase C.

PMID- 8743193
TI  - Naturally occurring IgG autoantibodies to platelet cytoskeleton tropomyosin.
AB  - We have observed that naturally occurring serum antibodies generated a 30 Kd band
      in a platelet immunoblot assay. The target protein had the same molecular weight
      (30 Kd) under nonreduced and reduced electrophoretic conditions, and could be
      immunoblotted from either autologous or homologous platelet lysates. Also, the 30
      Kd reactive autoantibodies could be totally adsorbed by platelet cytoskeletons.
      From these data one likely candidate for the autoantibody target was the
      intracellular platelet protein tropomyosin. Indeed, a commercially available
      monoclonal anti-tropomyosin antibody reacted with proteins comigrating with this
      30 Kd band; affinity purified human platelet tropomyosin was bound by the
      antibodies that recognized the 30 Kd protein. This body of evidence conclusively
      demonstrated that naturally occurring serum autoantibodies reacted with the
      platelet cyto-skeleton protein-tropomyosin. These tropomyosin specific antibodies
      were found in roughly the same percentage of sera from patients with chronic
      idiopathic thrombocytopenic purpura (ITP) as from normal individuals.

PMID- 8743194
TI  - Protein-tyrosine phosphorylation and p72syk activation in human platelets
      stimulated with collagen is dependent upon glycoprotein Ia/IIa and actin
      polymerization.
AB  - In human platelets treated with acetylsalicylic acid, collagen induced protein
      tyrosine-phosphorylation of several proteins. The major 75 kDa band included
      cortactin and auto-phosphorylated p72syk. p72syk activity rapidly increased upon
      collagen stimulation, whereas p60c-src activation was below detectable levels. A
      combination of inhibitors to remove the effects of extracellular and
      intracellular Ca2+, released ADP, and fibrinogen binding to GPIIb/IIIa delayed
      and attenuated the major 75 kDa band. By contrast, p72syk activation was not
      inhibited by these treatments. Cytochalasin D completely inhibited protein
      tyrosine phosphorylation and p72syk activation. It also potently inhibited
      aggregation and [Ca2+]i elevation. Anti-GPIa/IIa MoAb in a concentration
      dependent manner partially attenuated protein tyrosine phosphorylation and p72syk
      activation. Its inhibitory effects on intracellular Ca2+ mobilization, release of
      intracellular granule contents, and aggregation also were partial. No tyrosine
      kinase activity was coprecipitated with GPIa/IIa. These results suggest that
      p72syk activation lies upstream of protein tyrosine phosphorylation, Ca2+
      mobilization, ADP release, thromboxane A2 production and aggregation. GPIa/IIa
      plays a key role in p72syk activation induced by collagen, but other collagen
      receptors may work in synergy to fully activate p72syk. Actin polymerization is a
      prerequisite for both p72syk activation and other intracellular signal
      transduction pathways.

PMID- 8743195
TI  - Porcine von Willebrand factor binding to human platelet GPIb induces
      transmembrane calcium influx.
AB  - Porcine von Willebrand factor (P-vWF) binds to human platelet glycoprotein (GP)
      Ib and, upon stirring (1500 rpm/min) at 37 degrees C, induces, in a dose
      dependent manner, a transmembrane flux of Ca2+ ions and platelet aggregation with
      an increase in their intracellular concentration. The inhibition of P-vWF binding
      to GP Ib, obtained with anti GP Ib monoclonal antibody (LJ-Ib1), inhibits the
      increase of intracellular Ca2+ concentration ([Ca2+]i) and platelet aggregation.
      This effect is not observed with LJ-Ib10, an anti GP Ib monoclonal antibody which
      does not inhibit the vWF binding to GP Ib. An anti GP IIb-IIIa monoclonal
      antibody (LJ-CP8) shown to inhibit the binding of both vWF and fibrinogen to the
      GP IIb-IIIa complex, had only a slight effect on the [Ca2+]i rise elicited by the
      addition of P-vWF. No inhibition was also observed with a different anti GP IIb
      IIIa monoclonal antibody (LJ-P5), shown to block the binding of vWF and not that
      of fibrinogen to the GP IIb-IIIa complex. PGE1, apyrase and indomethacin show a
      minimal effect on [Ca2+]i rise, while EGTA completely blocks it. The GP Ib
      occupancy by recombinant vWF fragment rvWF445-733 completely inhibits the
      increase of [Ca2+]i and large aggregates formation. Our results suggest that, in
      analogy to what is seen with human vWF under high shear stress, the binding of P
      vWF to platelet GP Ib, at low shear stress and through the formation of
      aggregates of an appropriate size, induces a transmembrane flux of Ca2+,
      independently from platelet cyclooxygenase metabolism, perhaps through a receptor
      dependent calcium channel. The increase in [Ca2+]i may act as an intracellular
      message and cause the activation of the GP IIb-IIIa complex.

PMID- 8743196
TI  - Characterization of Fc gamma receptors on human megakaryocytes.
AB  - Megakaryocyte and platelet Fc gamma receptors (FcR) are of importance in the
      pathophysiology of immune complex-mediated thrombocytopenias such as heparin
      induced thrombocytopenia. In this study, Fc gamma R proteins and mRNAs in normal
      human megakaryocytes were examined. Fc gamma R proteins were studied with
      immunocytochemical staining, dual colour flow cytometry and immunoprecipitation
      using monoclonal antibodies against Fc gamma R I, Fc gamma R II and Fc gamma R
      III. Fc gamma R mRNAs were measured with biotinylated cDNA of oligonucleotide
      probes using a novel quantitative in situ hybridization technique. Using these
      techniques, Fc gamma R II protein and mRNA, but not Fc gamma R I and Fc gamma R
      III proteins and transcripts were detected in megakaryocytes. Further, transcript
      analysis showed that megakaryocytes contain only the transcript of Fc gamma R IIA
      gene but no transcripts of Fc gamma R IIB nor Fc gamma R IIC genes; Fc gamma R
      IIA transcripts with and without the transmembrane (TM) exon are present in
      approximately equal proportions. In contrast, neutrophils and macrophages also
      contain Fc gamma R IIA transcript but Fc gamma R IIA transcript with the TM exon
      predominates suggesting cell lineage-specific Fc gamma R IIA expression. Fc gamma
      R IIA transcript lacking the TM exon predicts the presence of a potential soluble
      form of Fc gamma R in platelets and megakaryocytes which may have a physiological
      role as it can compete with the membrane-bound Fc gamma R IIA for binding of IgG
      containing immune complexes and thus protect these cells from excessive binding
      and injurious effects of immune complexes.

PMID- 8743198
TI  - Heparin ablates force development during platelet mediated clot retraction.
AB  - Although snake venom enzymes such as reptilase do not cause viscous
      metamorphosis, platelet secretion or clot retraction; when batroxobin and calcium
      are added to citrated blood significant platelet force development occurs. When
      this batroxobin-calcium system was applied to the study of platelet function
      during cardiopulmonary bypass (CPB), force development was found to be completely
      inhibited. After heparin reversal by protamine sulfate, significant recovery of
      force occurred. The present investigation was performed to evaluate the role of
      heparin in reducing force development during CPB. At concentrations above 0.10
      U/ml, heparin totally suppressed force development in normal plasma. Addition of
      protamine sulfate to heparinized plasma caused complete recovery of force
      development. These concentrations of heparin had little effect on platelet
      aggregation by ADP or collagen. Possible direct effects of heparin on fibrin
      assembly and structure were studied by adding varying amounts of heparin to
      plasma and then inducing clot formation with batroxobin. At 1 U/ml, heparin
      reduced the size of fibrin fibers by 33%. Higher heparin concentrations had no
      additional effect. These results indicate that heparin may be responsible for a
      significant component of the decreased platelet force noted during
      cardiopulmonary bypass. To test whether heparin's effect could be due to
      suppression of thrombin activity, the effects of the antithrombin hirudin on
      force development were measured. Hirudin also inhibited force development in a
      concentration dependent manner. Thus, heparin's reduction of platelet force
      development may be due, at least in part, to suppression of thrombin activity.

PMID- 8743197
TI  - Non-isotopic method for quantitation of platelets and erythrocytes in
      experimental thrombi.
AB  - Experimental animal models of thrombosis have been established in several species
      to examine factors responsible for thrombotic disorders in man. One technical
      facet of all thrombosis models is the need to quantitate cell deposition on
      thrombogenic surfaces, and this is routinely accomplished with radioisotopic
      labeling of specific components. Data reported here demonstrate that formalin
      fixed thrombi can be hydrolyzed with chymotrypsin allowing recovery and
      quantitation of platelets and erythrocytes incorporated within the clot. Recovery
      of platelets from in vitro generated, model thrombi averaged 99 +/- 10% (mean +/-
      1 SD; n = 7; range 88-116%) of calculated content; recovery of erythrocytes was
      94.1 +/- 1.1% (n = 6) as measured by recovery of cellular hemoglobin after
      chymotrypsin hydrolysis of clots. Chymotrypsin was also shown to release
      platelets and erythrocytes from string-bound thrombi generated in vivo with an
      arterio-venous shunt model in beagle dogs. Platelet recovery from these string
      clots after chymotrypsin hydrolysis was independently verified with a
      quantitative Western blot assay of platelet antigens. These data demonstrate that
      experimental thrombi can be hydrolyzed with chymotrypsin, thereby not only
      eliminating the need for radioisotopes, but also permitting flow cytometric
      analysis of cells comprising the thrombus.

PMID- 8743199
TI  - Antiplatelet and antithrombotic effects of YM337, the Fab fragment of a humanized
      anti-GPIIb/IIIa monoclonal antibody in monkeys.
AB  - The antiplatelet and antithrombotic effects of the Fab fragment of the humanized
      antiplatelet glycoprotein (GP) IIb/IIIa monoclonal antibody C4G1 (YM337) were
      investigated in monkeys. First, the relationship between the inhibition of
      platelet aggregation and the prolongation of bleeding time was studied in rhesus
      monkeys. YM337 dose-dependently inhibited ex vivo platelet aggregation, with
      complete inhibition at doses higher than 0.25 mg/kg intravenous injection or 1.5
      micrograms/kg/min infusion. At 0.25 mg/kg bolus injection followed by 1.5
      micrograms/kg/min infusion, YM337 immediately and continuously inhibited platelet
      aggregation during the 6-h infusion period with platelet aggregation rapidly
      returning to over 50% of baseline within 1 h after the cessation of infusion.
      Template-bleeding time was significantly prolonged during the period of complete
      inhibition of platelet aggregation. Second, the antithrombotic effects of YM337
      were investigated in a photochemically-induced thrombosis model in squirrel
      monkeys. YM337 at a dose of 1 mg/kg intravenous injection followed by 6
      micrograms/kg/min infusion for 60 min prevented occlusive thrombus formation in
      all 4 monkeys. In contrast, time to occlusive thrombus formation did not change
      on intravenous bolus injection of aspirin 17 mg/kg (11.3 +/- 5.2 min) or sodium
      ozagrel (9.4 +/- 3.0 min) compared with saline (13.3 +/- 4.0 min). YM337 but not
      aspirin or sodium ozagrel significantly inhibited ex vivo ADP-induced platelet
      aggregation, while all drugs completely inhibited arachidonic acid-induced
      platelet aggregation. However, while aspirin and sodium ozagrel inhibited the
      thromboxane B2 generation accompanying arachidonic acid-induced platelet
      aggregation, YM337 had no effect on this variable. Platelet counts and bleeding
      time showed no significant change in any group in this squirrel monkey model.
      These results indicate that YM337, with a short half-life, may be a useful
      therapeutic agent in patients with thrombotic disorders.

PMID- 8743200
TI  - Collagen induced thrombus formation at the apex of eccentric stenoses--a time
      course study with non-anticoagulated human blood.
AB  - Atherosclerotic plaque rupture may trigger the formation of mural thrombus. This
      thrombus formation is apparently affected by very high and complex shear
      conditions introduced by the luminal narrowing (stenosis) of the atheroma. To
      study the impact of such blood flow behaviour on thrombus formation we employed a
      model system where collagen-induced thrombogenesis is studied at the apex of well
      defined eccentric stenoses. Thrombus formation in non-anticoagulated human blood
      drawn directly from an antecubital vein over the collagen coated stenosis apex
      for periods of 0.5, 1, 3 or 5 min was quantified by morphometry. The stenoses
      reduced the cross-sectional area of the blood flow channel by 60, 80 and 89%,
      which corresponded to apex wall shear rates of 2600, 10,500 and 32,000 s-1,
      respectively. Platelet-collagen adhesion decreased by increasing shear at the
      stenosis apex. The corresponding adhesion rates were highest at 1 min, then they
      gradually decreased upon prolongation of the perfusion time. The platelet
      thrombus volume increased in concert with increasing shear rate up to 10,500 s-1,
      whereas, at 32,000 s-1, the volume wa decreased. The corresponding growth rates
      and rates of thrombus occlusion at the apex levelled off at 3 min. Significant
      fibrin deposition was not observed before 3 min, and was most pronounced at
      10,500 and 32,000 s-1. The plasma levels of fibrinopeptide A and beta
      thromboglobulin increased in concert with increasing shear and perfusion time,
      particularly at the two highest shear conditions. Thus, hallmarks of thrombus
      formation at these stenoses with increasing shear are decreased platelet-collagen
      adhesion, and increased platelet-platelet interaction and fibrin deposition. A
      fibrin tail downstream to the collagen-attached platelet thrombus is regularly
      observed when thrombus occlusion exceeds 40%. However, the reduced thrombus
      growth at the most occlusive stenosis (89%) is presumably due to the high shear
      stresses which may reduce the rate of platelet incorporation into the thrombus
      and/or tear off thrombus fragments.

PMID- 8743201
TI  - Subnormal plasma von Willebrand factor (ristocetin cofactor) and iron deficiency
      anaemia in menstruating women.

PMID- 8743202
TI  - Frequency of factor V Arg506 Gln in Italians.

PMID- 8743203
TI  - Prevalence of mutant factor V in Italian patients with hereditary deficiencies of
      antithrombin, protein C or protein S.

PMID- 8743204
TI  - Frequency of antibodies directed against heparin-platelet factor 4 in patients
      exposed to heparin through chronic hemodialysis.

PMID- 8743205
TI  - Pseudo factor XII deficiency and phospholipid antibodies.

PMID- 8743206
TI  - The discrimination of factor XII deficiency and lupus anticoagulant.

PMID- 8743207
TI  - Dysautonomia in dogs: a retrospective study.
AB  - Dysautonomia was diagnosed in 11 young (median age, 14-months), predominantly
      medium- to large-breed dogs from 1988 to 1995. Clinical signs caused by autonomic
      dysfunction of the urinary, alimentary, and ocular systems were most common.
      Dysuria, mydriasis, absence of pupillary light reflexes, decreased tear
      production, dry mucous membranes, weight loss, and decreased anal tone were
      present in over 75% of affected dogs. Ocular pharmacological testing with a
      dilute (0.1%) solution of pilocarpine was used to demonstrate iris sphincter
      receptor function in all dogs. A low-dose (0.0375 mg/kg s.c.) bethanechol test
      and pharmacological testing with phenylephrine and epinephrine also demonstrated
      cholinergic and adrenergic receptor function in 4 dogs. All dogs died or were
      euthanized as a results of autonomic dysfunction. Neuronal depletion, with
      associated gliosis and minimal inflammation were noted histologically in the
      autonomic ganglia of each dog. The pelvic, ciliary, celiac, cranial cervical, and
      cranial and caudal mesenteric ganglia were affected in all dogs. The cause of
      autonomic failure in these dogs was not determined.

PMID- 8743208
TI  - Ultrasonographic characteristics of the adrenal glands in dogs with pituitary
      dependent hyperadrenocorticism: comparison with normal dogs.
AB  - Ultrasonographic evaluation of the adrenal glands was performed in 10 dogs with
      pituitary-dependent hyperadrenocorticism (PDH) and in 10 age- and weight-matched
      healthy control dogs. Thickness, shape, and echogenicity were determined for each
      adrenal gland. Adrenal thickness in dogs with PDH (median, 10 mm-left; 8.5 mm
      right) was significantly greater than thickness in control dogs (median, 6 mm
      left; 6 mm-right). Other ultrasonographic characteristics associated with PDH
      included bilaterally symmetrical adrenomegaly and maintenance of normal adrenal
      shape. Adrenal echogenicity was homogeneous and less than that of the adjacent
      renal cortex in 8 of 10 dogs with PDH and in 10 of 10 control dogs. Heterogenous
      echogenicity was present in 2 of 10 dogs with PDH, and was associated with
      nodular cortical hyperplasia in one of those dogs. Results of this study confirm
      the difference in sonographic appearance between PDH-induced bilateral cortical
      hyperplasia and functional adrenocortical neoplasia, and show a difference in
      sonographically determined adrenal size between healthy dogs and dogs with PDH.

PMID- 8743209
TI  - Basal and glucagon-stimulated plasma C-peptide concentrations in healthy dogs,
      dogs with diabetes mellitus, and dogs with hyperadrenocorticism.
AB  - Serum glucose and plasma C-peptide response to i.v. glucagon administration was
      evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs
      with insulin-treated diabetes mellitus, and 8 dogs with naturally acquired
      hyperadrenocorticism. Serum insulin response also was evaluated in all dogs,
      except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum
      insulin, and plasma C-peptide determinations were collected immediately before
      and 5, 10, 20, 30, and (for healthy dogs) 60 minutes after i.v. administration of
      1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated
      changes in plasma C-peptide and serum insulin concentrations were identical, with
      single peaks in plasma C-peptide and serum insulin concentrations observed
      approximately 15 minutes after i.v. glucagon administration. Mean plasma C
      peptide and serum insulin concentrations in untreated diabetic dogs, and mean
      plasma C-peptide concentration in insulin-treated diabetic dogs did not increase
      significantly after i.v. glucagon administration. The validity of serum insulin
      concentration results was questionable in 10 insulin-treated diabetic dogs,
      possibly because of anti-insulin antibody interference with the insulin
      radioimmunoassay. Plasma C-peptide and serum insulin concentrations were
      significantly increased (P < .001) at all blood sampling times after glucagon
      administration in dogs with hyperadrenocorticism, compared with healthy dogs, and
      untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C
      peptide peak response, total C-peptide secretion, and, for untreated diabetic
      dogs, insulin peak response and total insulin secretion were significantly lower
      (P < .00l) in diabetic dogs, compared with healthy dogs, whereas these same
      parameters were significantly increased (P < .01) in dogs with
      hyperadrenocorticism, compared with healthy dogs, and untreated and insulin
      treated diabetic dogs. Although not statistically significant, there was a trend
      for higher plasma C-peptide concentrations in untreated diabetic dogs compared
      with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline
      C-peptide concentrations also were significantly higher (P < .05) in diabetic
      dogs treated with insulin for less than 6 months, compared with diabetic dogs
      treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline
      plasma C-peptide concentrations greater than 2 SD (ie, > 0.29 pmol/mL) above the
      normal mean plasma C-peptide concentration; values that were significantly
      higher, compared with the results in healthy dogs (P < .001) and with the other
      35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide
      concentration during glucagon stimulation testing allowed differentiation among
      healthy dogs, dogs with impaired beta-cell function (ie, diabetes mellitus), and
      dogs with increased beta-cell responsiveness to glucagon (ie, insulin
      resistance). Plasma C-peptide concentrations during glucagon stimulation testing
      were variable in diabetic dogs and may represent dogs with type-1 and type-2
      diabetes or, more likely, differences in severity of beta-cell loss in dogs with
      type-1 diabetes.

PMID- 8743210
TI  - Urine cortisol:creatinine ratio in healthy and sick cats.
AB  - Urine cortisol:creatinine ratios (UCCR) were determined from single urine samples
      obtained by cystocentesis in 47 cats allotted into 2 groups: 31 healthy cats and
      16 sick, hospitalized cats with assorted clinical illnesses. The mean (+/-
      standard deviation) UCCR for healthy cats was 5.9 +/- 7.0 (median, 3.2; range,
      0.6 to 27.8). Age or gonadal status had no significant effect on the magnitude of
      UCCR within this group. However, sick cats had significantly higher UCCR (P =
      .002) when compared with healthy cats. The mean UCCR for sick cats was 19.6 +/-
      19.2 (median, 14.8; range, 1.7 to 75.1). This report establishes a reference
      range for UCCR in 31 normal cats and provides evidence that health status affects
      UCCR in cats.

PMID- 8743211
TI  - Thrombocytopenia in horses: 35 cases (1989-1994).
AB  - The records of 3,952 equine patients presenting to the Veterinary Teaching
      Hospital at North Carolina State University College of Veterinary Medicine were
      evaluated to determine risk factors associated with thrombocytopenia. Of 2,346
      horses from which a CBC was obtained, 35 (1.49%) were thrombocytopenic (platelet
      count < 75,000/microL). A reference population of 189 horses with normal platelet
      counts (75,000 to 300,000/microL) was also studied. Standardbred horses were at
      increased risk for thrombocytopenia, but age and gender were not identified as
      significant risk factors. Horses with infectious or inflammatory diseases were at
      increased risk for thrombocytopenia. The potential association of clinical and
      clinicopathologic factors with thrombocytopenia were assessed by reviewing a
      series of multiple logistic regression models. Clinical and clinicopathologic
      variables significantly associated with thrombocytopenia in the final model
      included increased PCV, increased band neutrophil count, increased total WBC, and
      decreased plasma protein concentration. Increased mature neutrophil count was
      associated with normal platelet counts. Thrombocytopenic horses were
      significantly more likely to die to be euthanized than were horses with normal
      platelet counts.

PMID- 8743212
TI  - Comparison of continuous versus intermittent enteral feeding in dogs.
AB  - In humans, continuous intragastric feeding has been suggested to cause fewer
      gastrointestinal (GI) adverse effects, better weight gain and nitrogen balance,
      and less glucose intolerance than bolus feeding. The aim of this study was to
      compare the GI adverse effects and the metabolic and nutritional consequences of
      intragastric feeding of an enteral formula (Jevity; Ross Laboratories, Columbus,
      OH) intermittently or continuously to dogs. Using a cross-over study design, 10
      healthy dogs were randomly assigned to be fed Jevity via gastrostomy tube either
      continuously (CF) or in 3 bolus meals/day (IF) for 10 days. The dogs were weighed
      daily. Serum chemistry and glucose tolerance tests (GTT) were performed before
      and after each 10-day trial period. Fecal dry matter (FDM), serum osmolality
      (sOsm), and serum electrolytes (sElec) were determined 5 times during each 10 day
      trial period. Urine specific gravity was checked intermittently. Hydrogen breath
      tests were performed on days 0, 3, and 10. During the last 6 days of each trial
      period, nitrogen balance and digestibility of the Jevity were determined. There
      were no GI adverse effects noted on either protocol, and no significant (P > .05)
      differences in body weights, serum chemistry results, sElec, sOsm, GTT, hydrogen
      breath tests, digestibility trials, or nitrogen balance. There was a significant
      (P < .05) decrease in FDM over time for both protocols, and a significant (P <
      .05) increase in urine volume for IF compared with CF. In summary, there were no
      significant differences between treatments in weight maintenance, GI adverse
      effects, GTT, nitrogen balance, or feed digestibility. Changes in FDM suggest
      that the dogs received excess water. In conclusion, this study of healthy dogs
      provides no support for the preferential use of continuous intragastric feeding
      over bolus feeding.

PMID- 8743213
TI  - Esophagitis due to Pythium insidiosum infection in two dogs.
AB  - Chronic esophagitis due to Pythium insidiosum infection caused weight loss,
      dysphagia, and hypersalivation in 2 dogs from rural Tennessee. Although dog 1
      presented for evaluation in December 1984 and dog 2 in October 1992, infection
      likely occurred during the previous summer by drinking fresh pond water
      containing zoospores. Hematologic testing revealed eosinophilia and
      hypergammaglobulinemia in one dog. An etiologic diagnosis was not made until
      postmortem evaluation when hyphae within necrotic and granulomatous cellular
      infiltrates in the esophageal wall were identified as P insidiosum by
      immunoperoxidase staining. Failure to culture the organism from the esophageal
      wall in dog 2 was attributed to refrigeration of the tissues, since refrigeration
      decreases the survivability of P insidiosum.

PMID- 8743215
TI  - Discriminating or discrimination?

PMID- 8743214
TI  - Large animal internal medicine residency programs.

PMID- 8743216
TI  - Genetic testing and the ophthalmologist: does know mean no?

PMID- 8743217
TI  - Update in cataract and refractive surgery.

PMID- 8743218
TI  - Choroidal and retinal blood flow changes in degenerative myopia.
AB  - OBJECTIVE: To determine changes in choroidal and retinal blood flow in myopic
      retinopathy. DESIGN: Case-control study. SETTING: Ophthalmology department of a
      university-affiliated hospital in Elazig, Turkey. SUBJECTS: Twenty-one
      consecutive patients (40 eyes) with degenerative myopia and 20 age-matched
      healthy emmetropic volunteers (38 eyes). Both groups were free of any systemic
      disease, such as diabetes mellitus or hypertension, that can affect micro- or
      macrocirculation. OUTCOME MEASURES: Posterior ciliary artery and central retinal
      artery peak systolic, peak diastolic and mean blood flow velocity (measured with
      colour Doppler ultrasonography), pulsatility index and resistance index. RESULTS:
      The posterior ciliary artery mean peak systolic (12.34 vs. 16.90 cm/s) and peak
      diastolic (3.12 vs. 5.10 cm/s) blood flow velocity values were significantly
      lower in the study group than in the control group (p < 0.001). There was a
      significant difference in the posterior ciliary artery resistance index between
      the two groups (0.74 vs. 0.69) (p < 0.05). The central retinal artery mean peak
      systolic (6.64 vs. 9.72 cm/s) and peak diastolic (2.01 vs. 3.07 cm/s) blood flow
      velocity values were also significantly lower in the study group than in the
      control group (p < 0.001). CONCLUSION: Choroidal and retinal blood flow was
      decreased in degenerative myopia. The reduced choroidal blood flow may be partly
      due to increased vascular resistance. Decreased retinal blood flow is probably an
      adaptive change.

PMID- 8743219
TI  - Inhaled steroids: effect on intraocular pressure in patients without glaucoma.
AB  - OBJECTIVE: To evaluate the risk of intraocular pressure (IOP) elevation in
      patients receiving inhaled steroid therapy. DESIGN: Prospective study. SETTING:
      Four private practices in New Jersey. PATIENTS: A total of 187 patients (99 men
      and 88 women) with no documented history of glaucoma about to begin inhaled
      steroid therapy for various pulmonary conditions were enrolled. Of the 187, 183
      were followed at 12 weeks. INTERVENTIONS: Measurement of the IOP with the Tono
      Pen before therapy was started and 12 weeks after therapy was started. OUTCOME
      MEASURE: IOP. RESULTS: No significant rise in IOP was observed. No patient had a
      rise in IOP greater than 4 mm Hg. CONCLUSIONS: Although isolated case reports
      indicate a definite risk of glaucoma in the presence of inhaled steroid therapy,
      the risk appears to be small.

PMID- 8743220
TI  - Reducing the risk of needle-stick injury during orbital fine-needle aspiration
      biopsy.

PMID- 8743222
TI  - Epibulbar fibrous histiocytoma in a child.

PMID- 8743221
TI  - Late postoperative hypotony and choroidal detachment.

PMID- 8743223
TI  - Anterior pyramidal cataracts in Ehlers-Danlos syndrome.

PMID- 8743224
TI  - Toxicity of intravitreal interferon alpha-2b in the rabbit.

PMID- 8743225
TI  - Pediatric ophthalmology.

PMID- 8743227
TI  - Incidence of hepatitis C in patients with chronic elevations of
      aminotransferases.
AB  - BACKGROUND: We undertook a study to determine the incidence of hepatitis C in
      patients with persistent elevations of aminotransferases, either alanine
      aminotransferase (ALT) or aspartate aminotransferase (AST). METHODS: We conducted
      a retrospective review of medical records at the Family Practice Center from 1992
      to 1993. Patients in whom aminotransferase levels were elevated 1.5 times normal
      for at least 6 months were eligible for the study. Sixty patients met our
      eligibility criteria. Patients were tested for hepatitis B and C and other
      possible causes of elevated aminotransferase levels. RESULTS: Of these 60
      patients, 35 (58 percent) tested positive for hepatitis C virus by first
      generation enzyme-linked immunosorbent assay (ELISA-I); 30 had positive results
      confirmed by second-generation recombinant immunoblot assay (RIBA-II). The other
      5 patients were lost to follow-up, and their status was not confirmed. Of the 30
      patients with a positive RIBA-II, 14 had liver biopsies showing chronic
      persistent hepatitis or chronic active hepatitis, both consistent with hepatitis
      C infection. Of the 60 patients, 2 (3 percent) had hepatitis B. None had active
      hepatitis B coexisting with hepatitis C. CONCLUSIONS: Our data show a much
      greater incidence of hepatitis C (50 percent) in our patients with chronic
      elevations of aminotransferase levels compared with data reported from previous
      studies.

PMID- 8743228
TI  - Detection of human papillomavirus DNA in patients referred to a family practice
      colposcopy clinic.
AB  - BACKGROUND: Human papillomavirus (HPV) is strongly implicated in the pathogenesis
      of cervical neoplasia. The ability of a commercially available kit
      (Virapap/Viratype) to detect evidence of HPV is compared with cervical cytology,
      colposcopy, and directed biopsies. METHODS: During a period of 16 months,
      cervical samples from 241 consecutive new patients referred for a colposcopy
      examination were obtained for HPV-DNA hybridization typing according to the kit
      instructions. Samples were sent to a reference laboratory for testing. The
      results were compared with results of the colposcopy examination, cervical
      cytology, and directed cervical biopsy samples processed and evaluated by our
      hospital laboratory. RESULTS: HPV DNA was detected in 27 of 107 patients who had
      abnormal colposcopy findings for a sensitivity of 25 +/- 7.5 percent at the 90
      percent confidence interval. One of 134 patients with normal findings was
      positive for a specificity of 99 +/- 5 percent at the 95 percent confidence
      interval. Based on a 75 percent probability of HPV in the population, the
      positive predictive value was 99 percent and the negative predictive value 30
      percent. CONCLUSIONS: With the low negative predictive value and sensitivity, HPV
      DNA testing by this commercial kit is not an adequate tool for screening HPV in
      this population.

PMID- 8743229
TI  - Physicians' attitudes and beliefs about deaf patients.
AB  - BACKGROUND: We wanted to validate reports that deaf persons have difficulty
      obtaining medical care by comparing physicians' attitudes towards these patients
      with physicians' attitudes toward their patients in general. METHODS: Two
      questionnaires were randomly distributed to physicians attending continuing
      medical education conferences at the University of Michigan during a 3-month
      period. The questionnaires were identical except that one asked about deaf
      patients and the other about patients in general. The questions assessed the
      respondent's perceptions of communication with patients, attitudes toward their
      patients, knowledge of current information about deaf people, and demographics.
      RESULTS: One hundred sixty-five physicians responded, 94 to the general
      questionnaire and 71 to the deaf questionnaire. The two physician groups were
      similar demographically, but 165 differed significantly in communication and
      attitude variables. Physicians receiving the questionnaire focusing on deaf
      patients reported greater difficulties in understanding (P < 0.001) and
      maintaining free-flowing conversations (P < 0.001), and that these patients had
      more difficulty understanding them (P < 0.001), trusted them less (P < 0.001),
      asked them to repeat statements more often (P < 0.001) and were less likely to
      understand the diagnosis and recommended treatments (P < 0.001). Physicians also
      reported feeling less comfortable with deaf patients (P < 0.001) and that they
      asked fewer questions (P < 0.001). Physicians were more likely to say that deaf
      patients rely on interpreters (P = 0.040), get frustrated easily (P < 0.001), and
      are harder to communicate with (P < 0.001). There were no significant differences
      between the two groups in knowledge about deaf people. All physicians, however,
      displayed ignorance about their legal obligations under the Americans with
      Disabilities Act to provide interpreters for their deaf patients. CONCLUSIONS:
      Physicians surveyed about deaf patients reported significantly greater
      difficulties communicating with and different attitudes toward these patients
      than physicians surveyed about their patients in general. All physicians were
      unaware of their obligations under the Americans with Disabilities Act to provide
      interpreters for deaf patients. Research is needed to determine whether physician
      attitudes and beliefs affect the actual quality of care they deliver to deaf
      patients.

PMID- 8743230
TI  - The practice of obstetrics by Army family physicians.
AB  - BACKGROUND: There has been a dramatic decline nationwide in family physicians
      practicing obstetrics. This study describes the practice of obstetrics by Army
      family physicians in an environment relatively free of malpractice liability and
      other financial concerns. METHODS: A questionnaire was mailed to every family
      physician on active duty in the Army (n = 334) in 1993, with a final response
      rate of 79 percent (n = 265). RESULTS: Nearly 73 percent of Army family
      physicians practice obstetrics. Almost all believed they were adequately prepared
      to provide routine prenatal care (98 percent) and complicated obstetric care (84
      percent). More than 95 percent of those assigned to a teaching facility delivered
      babies. Obstetric procedures that the majority performed included normal vaginal
      deliveries (100 percent), repair of third-degree (98 percent) and fourth-degree
      (93 percent) tears, insertion of fetal scalp electrodes (96 percent) and
      intrauterine pressure catheters (98 percent), interpretation of nonstress tests
      (97 percent) and contraction stress tests (83 percent), vacuum extractions (93
      percent), pudendal or paracervical blocks (88 percent), first assist in Cesarean
      sections (80 percent), amnioinfusions (76 percent), and low-forceps deliveries
      (53 percent). Those who currently practice obstetrics were more satisfied with
      being a family physician compared with those who did not practice obstetrics (95
      percent vs 86 percent, P < 0.02). CONCLUSIONS: The majority of Army family
      physicians perform a wide spectrum of obstetrics care. Those who practiced
      obstetrics were generally more satisfied with family practice than were those who
      did not practice obstetrics.

PMID- 8743231
TI  - Asthma as an inflammatory disease: implications for management.
AB  - BACKGROUND: Eosinophilic inflammation plays a central role in the pathogenesis of
      asthma. Striking inflammatory changes are present in the airways of patients with
      all levels of disease severity. The degree of airway inflammation correlates with
      airway hyperresponsiveness, the primary physiologic abnormality of asthma.
      Inflammation is typically initiated by immunologic events (including allergy) and
      is driven by mediators released by various cells of the immune system,
      particularly eosinophils, monocytes and macrophages, lymphocytes, and mast cells.
      METHODS: Literature on asthma and the inflammatory response was drawn from recent
      articles presented and reviewed in journal clubs and from selected articles from
      the National Library of Medicine. RESULTS AND CONCLUSIONS: The inflammatory
      process can be divided into six steps: triggering, signaling, migration,
      inflammatory cell activation, tissue damage, and resolution. Recognition of the
      importance of inflammation in the pathogenesis of asthma and the progression of
      the disease has shifted research efforts and the development of new therapeutic
      agents toward reduction of airway inflammation. Anti-inflammatory therapy, which
      can be directed against specific steps in the inflammatory process, actually
      reduces bronchial hyperresponsiveness. Although anti-inflammatory management has
      assumed a primary role in asthma therapy, short acting beta 2-adrenergic receptor
      agonists are needed for treatment of acute symptoms, and some patients require
      regular beta 2-agonist therapy despite apparently adequate anti-inflammatory
      therapy.

PMID- 8743232
TI  - Chronic opioid analgesic therapy for chronic low back pain.
AB  - BACKGROUND: Eleven percent of American adults have chronic low back pain- and
      many of these individuals have severe, disabling, refractory pain. Many texts
      recommend against using opioids for these patients without citing original
      research. METHODS: A MEDLINE literature search was conducted for original
      research on the use of opioids for chronic noncancer pain. Additional references
      were also sought from review articles and book chapters. Based on this research
      and the authors' clinical experience, recommendations were formulated for
      implementing chronic opioid analgesic therapy (COAT) for patients with chronic
      low back pain. RESULTS: No controlled studies were found. Case series reports on
      a total of 566 patients suggest that COAT is safe and effective for many patients
      with recalcitrant chronic low back pain. Preexisting substance use disorders,
      personality disorders, certain medical conditions, and certain occupational
      factors are relative contraindications to COAT. Methods to prevent and monitor
      for drug problems among COAT recipients include contracts, family interviews, and
      drug testing. Pain and overall function are the key monitoring parameters. Once
      patients attain some relief, an exercise regimen should be initiated. Other
      nonpharmacologic treatments and nonopioids are also recommended. CONCLUSION:
      Physicians are encouraged to consider COAT for selected patients with severe
      chronic low back pain who respond inadequately to other treatments.

PMID- 8743233
TI  - Helicobacter pylori in peptic ulcer disease: report of an NIH consensus
      conference.

PMID- 8743234
TI  - The limits of state action? The myths and realities of ERISA. Employee Retirement
      Income Security Act.

PMID- 8743235
TI  - EDTA-induced pseudothrombocytopenia.

PMID- 8743236
TI  - Early removal of the Norplant System.

PMID- 8743237
TI  - Bulging anterior fontanel associated with apparent benign intracranial
      hypertension.

PMID- 8743238
TI  - Chronic opioids for chronic low back pain--solution or problem?
AB  - The article by Brown et al does not provide data to justify long-term opioid use
      but does suggest a treatment option for the many patients who have chronic back
      pain and who want the help that our medical delivery system often does not
      provide. Having worked in a tertiary referral pain clinic that serves many low
      back pain patients who have demonstrated the ineffectiveness of chronic opiate
      therapy, I am strongly ambivalent about recommending prescribing ongoing opioiod
      therapy for chronic pain patients. The caveats about prescribing opioids for such
      patients are most appropriate (i.e., do not prescribe opioids for those who have
      a history of problems with opioid therapy or for whom increased intake is
      associated with decreased function); however, for patients who do not display
      these problems (and there could be many out there), I am sympathetic with the
      sentiments expressed by Brown et al. A trial of these drugs might be warranted if
      all else fails and continued therapy with opioids seems justified, but only with
      zealous attention to monitoring function and therapeutic compliance, as outlined
      by the authors. With regard to the doses needed for control, the method of opioid
      administration might be important, that is, whether it is in tablets or in a
      masking vehicle. In this day of open dialogue, it is not fashionable to blind the
      patient to the drug or dose, but I believe blinding has a place in the care of a
      particular group of patients whose symptom (pain) can vary considerably with
      time. I have found that most chronic pain patients rarely, if ever, reduce their
      analgesic intake in better times, but an attentive physician can if masking
      vehicles are used. Thus the physician can limit the amount of drug consumed long
      term. In my personal experiences with comparable chronic nonmalignant pain
      patients (albeit in different hemispheres), the average opioid maintenance
      (methadone) dosage was halved by prescribing the drug in a masking vehicle rather
      than as a tablet. If pain complaints are reduced and if function is improved
      according to the record (eg, patient is working) and the relatives' report, and
      if you, the prescribing physician, are happy, then a long-term regimen of opioid
      therapy is probably fine. Further controlled trials are needed to see whether
      this therapy works, and if so, what are the optimal agent(s) and dosages, what is
      optimal monitoring, and most important of all, who is the optimal patient who
      might derive not only analgesia but also functional benefit rather than
      compromise from this therapy. If we cannot make patients better, we must not make
      them worse.

PMID- 8743239
TI  - Epidural anesthesia and cesarean section.

PMID- 8743240
TI  - Expansion of training in family medicine.

PMID- 8743242
TI  - Scales, diagnoses, and child psychopathology: II. Comparing the CBCL and the DISC
      against external validators.
AB  - Using a multimethod multistage screening procedure, the authors interviewed 201
      parents and their children with the Diagnostic Interview Schedule for Children
      (DISC 2.1). In addition, parents completed the Child Behavior Checklist (CBCL)
      and other survey measures, while their children completed self-report scales.
      Receiver operating characteristic (ROC) analyses were done to determine optimal
      cutpoints on the CBCL, referenced to DISC diagnostic "caseness." DISC diagnoses,
      DISC "stem" symptoms, CBCL scores, and CBCL ROC-outpoints were compared against
      "external validators," in order to determine the comparative advantages of each
      approach for assessing child psychopathology. Overall findings suggest that the
      controversies about "best" assessment strategies may be artificial: When both
      assessment approaches are compared using similar methods, they are reasonably
      comparable. However, highly specific diagnostic categories may show fewer
      relationships with external validators and may therefore need more systematic
      validational studies.

PMID- 8743241
TI  - A multiple-risk interaction model: effects of temperament and divorce on
      psychiatric disorders in children.
AB  - Effects of family status on the trajectory of problematic temperament-adjustment
      at 1 and 10 years of age and associated psychiatric disturbance 8 years later
      were examined in an epidemiological sample of 648 children. After adjusting for
      predivorce temperament-adjustment and background factors, logistic regression
      yielded independent effects of single custodial mother (SCM) family status for
      increased risk of disruptive and anxiety disorders, and of stepfamily status for
      increased risk of disruptive disorders. Increased risk of psychiatric disorders
      was more pervasive for SCM family boys versus intact family boys than for SCM
      family girls versus intact family girls, however only significantly more so for
      depression. No significant sex interaction was observed for stepfamily status.
      When girls and boys were treated independently, patterns of family status and
      outcomes of internalizing disorders varied. In stepfamilies, an elevated risk of
      depression and anxiety disorders was observed in girls but not boys, whereas in
      SCM families an elevated risk of depression was observed in boys but not girls.
      Within each family status group there was support for an altered risk of later
      psychiatric disorders given specific problematic predivorce temperament
      adjustment characteristics. Implications for future research and treatment are
      discussed.

PMID- 8743243
TI  - What they want and what they get: the social goals of boys with ADHD and
      comparison boys.
AB  - Twenty-seven boys diagnosed with attention-deficit hyperactivity disorder (ADHD)
      and 18 comparison boys participated in a competitive tetradic interaction task.
      Boys were individually interviewed before the game about their goals for the
      interaction, and adult observers inferred boys' social goals from videotapes of
      the interaction. Social acceptance was determined by combining positive and
      negative sociometric nominations collected through individual interviews at the
      end of the summer research program in which the interaction was held. In their
      self-reports, ADHD-high aggressive boys prioritized trouble-seeking and fun at
      the expense of rules to a greater extent than did both ADHD-low aggressive and
      comparison boys. Observers judged ADHD-high aggressive boys to seek attention
      more strongly and seek fairness less strongly than of the other two groups. Self
      reported goals of defiance and cooperation predicted boys' end-of-program social
      standing, even with interactional behaviors and subgroup status controlled
      statistically. Observer-inferred goals were differentially associated with social
      acceptance for ADHD and comparison boys, suggesting discontinuities in peer
      interaction processes. Differentiation of goals from behavior and the integral
      role of children's goals in peer acceptance are discussed.

PMID- 8743244
TI  - Family enhancement of cognitive style in anxious and aggressive children.
AB  - Previous research has shown that anxious adults provide more threat
      interpretations of ambiguous stimuli than other clinic and nonclinic persons. We
      were interested in investigating if the same bias occurs in anxious children and
      how family processes impact on these children's interpretations of ambiguity.
      Anxious, oppositional, and nonclinical children and their parents were asked
      separately to interpret and provide plans of action to ambiguous scenarios.
      Afterwards, each family was asked to discuss two of these situations as a family
      and for the child to provide a final response. The results showed that anxious
      and oppositional children were both more likely to interpret ambiguous scenarios
      in a threatening manner. However, the two clinic groups differed in that the
      anxious children predominantly chose avoidant solutions whereas the oppositional
      children chose aggressive solutions. After family discussions, both the anxious
      children's avoidant plans of action and the oppositional children's aggressive
      plans increased. Thus, this study provides the first evidence of family
      enhancement of avoidant and aggressive responses in children. These results
      support a model of anxiety that emphasizes the development of an anxious
      cognitive style in the context of anxiety-supporting family processes.

PMID- 8743245
TI  - The role of adolescent peer affiliations in the continuity between childhood
      behavioral adjustment and juvenile offending.
AB  - This research reports on a structural equation model analysis of the
      relationships between childhood behavioral adjustment, adolescent peer
      affiliations, and adolescent offending using data gathered during the course of a
      16-year longitudinal study of a birth cohort of New Zealand children. The model
      developed contained parameters that estimated (a) the continuities between early
      behavior and later offending, (b) the associations between early behavior and
      adolescent peer affiliations, and (c) the potentially reciprocal relationship
      between adolescent peer affiliations and adolescent offending behaviors. This
      analysis suggested that, when due allowance was made for reporting error, there
      was evidence of relatively strong continuity (r = .50) between early behavior and
      later offending. The model estimates suggested that these continuities arose from
      both direct continuities in behavior over time and from the effects of adolescent
      peer affiliations in reinforcing and sustaining earlier behavioral tendencies.
      The implications of the analysis for the understanding of the role of adolescent
      peer affiliations in behavioral continuities and discontinuities are discussed.

PMID- 8743246
TI  - Reward dominance: associations with anxiety, conduct problems, and psychopathy in
      children.
AB  - The associations between children's behavior and their performance on a task with
      a steadily increasing ratio of punished to rewarded responses was investigated in
      a group of clinic-referred (n = 92) and normal control (n = 40) children between
      the ages of 6 and 13. Clinic-referred children with an anxiety disorder played
      significantly fewer trials than clinic-referred children without an anxiety
      disorder but the response style of the anxious children did not differ from that
      of a normal control group. Children with severe conduct problems who had no
      anxiety disorder played more trials than (a) children with severe conduct
      problems and a comorbid anxiety disorder, (b) nonanxious children with attention
      deficit hyperactivity disorder, and (c) children in the normal control group. The
      strongest evidence for the reward dominant response style was for nonanxious
      subjects with elevations on a measure of psychopathic features, irrespective of
      whether they also had conduct problems and irrespective of whether they were
      clinic-referred.

PMID- 8743247
TI  - Laboratory diagnosis of syphilis.

PMID- 8743248
TI  - Gonorrhoea.

PMID- 8743249
TI  - Chancroid.

PMID- 8743250
TI  - Chlamydia trachomatis infections in women.

PMID- 8743251
TI  - Bacterial vaginosis.

PMID- 8743252
TI  - Genital candidosis.

PMID- 8743253
TI  - Diagnosis of genital herpes simplex infections.

PMID- 8743254
TI  - Viral hepatitis.

PMID- 8743255
TI  - Human papillomavirus infections.

PMID- 8743256
TI  - Diagnosing sexually transmitted diseases in HIV-positive patients.

PMID- 8743257
TI  - Gonorrhoea: single-dose oral treatment.

PMID- 8743258
TI  - Chancroid.

PMID- 8743259
TI  - Nongonococcal urethritis.

PMID- 8743260
TI  - Bacterial vaginosis.

PMID- 8743261
TI  - Chlamydia trachomatis: a major cause of mucopurulent cervicitis and pelvic
      inflammatory disease in women.

PMID- 8743262
TI  - Genital candidosis.

PMID- 8743263
TI  - Genital herpes.

PMID- 8743264
TI  - Clinical aspects of genito-anal papillomavirus infection with a focus on when and
      how to investigate.

PMID- 8743265
TI  - Scabies treatment: current considerations.

PMID- 8743266
TI  - Infestations: pediculosis.

PMID- 8743267
TI  - Treating sexually transmitted diseases in pregnancy.

PMID- 8743268
TI  - Application of DNA-based technologies in the diagnosis of sexually transmitted
      diseases.

PMID- 8743269
TI  - Azithromycin.

PMID- 8743270
TI  - Itraconazole and therapy of fungal infections.

PMID- 8743271
TI  - Fluconazole: its properties and efficacy in vaginal candidiasis.

PMID- 8743272
TI  - Aciclovir and its l-valyl ester, valaciclovir.

PMID- 8743273
TI  - Use of penciclovir and famciclovir in the management of genital herpes.

PMID- 8743274
TI  - Podophyllotoxin in the treatment of genital warts.

PMID- 8743275
TI  - Interferons.

PMID- 8743276
TI  - Laser therapy.

PMID- 8743277
TI  - Permethrin.

PMID- 8743278
TI  - Gonadotropin levels in women with polycystic ovary syndrome: their relationship
      to body weight and insulin levels.
AB  - The purpose of this work was to investigate the relationship of gonadotropin
      levels to body weight and insulin levels in woman with polycystic ovary syndrome
      (PCOS). Specifically, we wished to test the hypothesis that circulating
      luteinizing hormone (LH) and insulin levels are different in obese and normal
      weight patients with PCOS. The basal plasma levels of gonadotropins, estrogens,
      androgens and sex hormone-binding globulin, the gonadotropin responses to
      gonadotropin releasing hormone (GnRH) and the insulin and C-peptide responses to
      a 3-hour oral glucose tolerance test (OGTT) were measured in 19 obese and 19
      normal weight patients with PCOS and 7 obese and 8 normal weight ovulatory
      controls. Data of the patients were evaluated according to body weight (obese vs
      normal weight) and basal LH (high vs normal). There was no significant difference
      in basal LH and androgen levels and in the insulin response to oral glucose
      between obese and normal weight patients with PCOS. Compared to the weight
      matched controls, both obese and non obese patients showed significantly higher
      LH responses to GnRH and C-peptide responses to OGTT. When the high LH patients
      (no = 18) were compared those with normal LH (no = 20), the high LH subjects
      exhibited significantly higher androstenedione levels. Both obese (no = 10) and
      normal weight (no = 8) patients with high LH showed significantly greater C
      peptide responses to OGTT than obese (no = 9) and non obese (no = 11) patients
      with normal LH. However, as compared with the weight matched controls, both the
      high LH and normal LH patients had significantly greater C-peptide responses to
      OGTT. We conclude that obese and non obese patients with PCOS do not seem to
      differ in the prevalence of elevated LH levels or in the LH secretory pattern.
      Insulin resistance, expressed by an enhanced pancreatic sensitivity to oral
      glucose, is present in both the high LH and the normal LH subjects, even though
      the PCOS patients with elevated LH tend to be more insulin resistant and
      hyperandrogenic than the normal LH patients.

PMID- 8743279
TI  - Transforming growth factor-alpha regulates subpopulation of giant cells which
      secrete mouse placental lactogen-I (mPL-I) and/or mPL-II at midpregnancy.
AB  - The aim of this study was to determine whether transforming growth factor-alpha
      (TGF-alpha) regulates expression of mouse placental lactogen-I (mPL-I) and mPL-II
      at midpregnancy in vitro. Treatment of placental cells from day 9 of pregnancy
      with TGF-alpha resulted in stimulation of mPL-I secretion and inhibition of mPL
      II secretion in a time- and dose-dependent manner without changing the amount of
      newly synthesized trichloroacetic acid precipitable proteins and cell viability.
      Moreover, TGF-alpha increased the intra-cellular mPL-I concentration and immuno
      precipitable newly synthesized mPL-I concentration both in the medium and cells.
      TGF-alpha increased the number of cells containing only mPL-I and cells
      containing both mPL-I and mPL-II, but decreased that of the cells containing only
      mPL-II assessed by double immunocytochemistry. TGF-alpha increased the number of
      cells releasing only mPL-I but decreased the number of cells releasing only mPL
      II, however TGF-alpha did not affect the number of cells releasing both mPL-I and
      mPL-II assessed by sequential reverse hemolytic plaque assay (RHPA). TGF-alpha
      decreased the expression of mPL-II mRNA, but did not change the expression of mPL
      I mRNA. In situ hybridization for epidermal growth factor receptor (EGF-R) after
      RHPA for mPL-I indicated that giant cells releasing mPL-I express EGF-R mRNA.
      These findings suggest that TGF-alpha regulates the subpopulation of giant cells
      which produces and releases mPL-I and mPL-II and it results in an increase of mPL
      I secretion and decrease of mPL-II secretion, and suggests possible post
      transcriptional stimulation of mPL-I secretion and transcriptional inhibition of
      mPL-II secretion by TGF-alpha. Giant cells releasing mPL-I express EGF-R mRNA,
      suggesting direct regulation of giant cell differentiation by EGF and TGF-alpha
      at midpregnancy.

PMID- 8743280
TI  - Galactosylhydroxylysine and pyridinium cross links in monitoring the bone
      response to hormone replacement therapy.
AB  - Aim of the study was to compare urinary galactosyl-hydroxylysine (GHyl),
      deoxypyridinoline (D-Pyr) and pyridinoline (Pyr) before and after 5 to 9 months
      of hormone replacement therapy (HRT) in postmenopausal women. The urinary markers
      were measured by HPLC in the second void of fasting samples and were expressed as
      ratio to creatinine. GHyl was also expressed as a ratio to glucosylgalactolysyl
      hydroxylysine (GGHyl). After short-term hormone replacement therapy, urinary D
      Pyr fell significantly, but Pyr and GHyl, also when expressed as a ratio to
      GGHyl, remained unmodified. We conclude that GHyl and Pyr are not useful markers
      in monitoring the bone response to HRT in postmenopausal women.

PMID- 8743281
TI  - Relevance of estrogen and progesterone receptors enzyme immunoassay in malignant,
      benign and surrounding normal thyroid tissue.
AB  - Several authors have demonstrated the presence of estrogen receptors (ER) and
      progesterone receptors (PR) in thyroid tissue, generally using dextran coated
      charcoal method (DCCA). The aim of the study was to measure ER and PR in thyroid
      specimens using an immunoenzymatic method, and to evaluate the meaning of
      different prevalence of ER and PR in malignant and benign thyroid disease, as
      compared with normal thyroid tissue. We have measured ER and PR in thyroid tissue
      from 28 benign and 20 malignant thyroid lesions, and in 38 samples of surrounding
      normal thyroid tissues. The sensitivity of ER-EIA and PR-EIA was 1.0 and 1.5
      fmol/mg protein, respectively. In thyroid carcinoma the frequency of ER
      positivity (ER+) was 7/20 (35%); it was significantly higher in the surrounding
      normal tissue (15/20; 71%) (p = 0.03). In benign thyroid disease, the prevalence
      of ER+ was 11/28 (39%) and in the surrounding normal tissue it was 11/18 (61%) (p
      = not significant). PR+ was detected in 7/20 (35%) thyroid cancers and in 15/28
      (53%) benign lesions without significant difference with the frequency detected
      in the surrounding normal tissues. ER and PR concentrations (mean +/- SD) in
      thyroid cancer was 2.2 +/- 2.2 and 2.2 +/- 2.9 respectively, similarly to that
      detected in benign thyroid disease and in normal tissue. The simultaneous
      presence of ER and PR (ER+PR+) was also evaluated. We have found that the
      frequency of ER+ PR+ was significantly higher in benign lesions (8/28; 28.6%) as
      compared with malignant samples (1/20; 5%) (p < 0.05); the frequency of ER+PR+
      was significantly higher in normal tissue surrounding the malignant lesions
      (9/20; 45) (p = 0.003). Our data indicate i) EIA method is appropriate to detect
      ER and PR in thyroid tissue. ii) The frequency of ER+ and ER+PR+ specimens is
      significantly higher in normal thyroid tissue than in pathologic tissues. This
      indicates that ER and PR immunoassays may be useful tools to evaluate the normal
      biological activity of thyroid cells.

PMID- 8743282
TI  - The primary role of steroids on the osteoporosis in juvenile rheumatoid patients
      evaluated by dual energy X-ray absorptiometry.
AB  - Osteoporosis, a common clinical feature in children affected with Juvenile
      Rheumatoid Arthritis (JRA), is generally divided into two forms, a localized
      juxta-articular osteoporosis of the single joints and a generalized reduction of
      bone mass due to the disease itself, joint involvement and steroid treatment.
      Recently Dual Energy X-ray Absorptiometry (DEXA) has been suggested for Bone
      Mineral Density (BMD) measurement. In the present study DEXA has been used to
      investigate the lumbar spine BMD in JRA patients as compared to healthy children.
      Our results showed that BMD is reduced in JRA patients (BMD 0.685 g/cm2) when
      compared to healthy children (BMD 0.722 g/cm2), and it is significantly lower in
      the group of patients treated with steroids (BMD 0.623 g/cm2) when compared to
      those treated with nonsteroidal antiinflammatory drugs (BMD 0.710 g/cm2). The
      analysis of all risk factors of bone loss indicated that steroids represent the
      only parameter of significant negative correlation with BMD.

PMID- 8743283
TI  - Increased risk of autoimmune hypothyroidism in patients affected by retinitis
      pigmentosa.
AB  - Patients with Retinitis Pigmentosa (RP) show hemeralopia, restricted field of
      vision and reduced visual acuity, owing to the degeneration and proliferation of
      photoreceptors and a retinal pigment epithelium. The prevalence in Italy is
      1:4,000. A certain number of "syndromic" associations have been described, and,
      in particular, also that with hypothyroidism, but very few cases have been
      studied. We describe a family of 40 people, spanning four generations, in which
      we have recorded the presence of autosomic dominant RP, associated with
      autoimmune hypothyroidism or with circulating antithyroid autoantibodies (ATA),
      currently considered as the expression of active autoimmune thyroiditis or a risk
      factor for this complaint. We measured, in all members, TSH, FT3, FT4,
      antithyroglobulin and antithyroperoxidase autoantibodies. A fundus oculi
      examination was performed in every subject, as well as a careful examine of the
      anterior region on the neck. A control population of 100 healthy people was also
      studied. Our data show a higher prevalence of ATA, statistically significant, in
      the patients with RP and in their relatives, compared with the control population
      and the data from the literature (13 cases over 40 = 32.5%; p < 0.01). 3 patients
      with RP and ATA were affected by clinically evident hypothyroidism. 10 patients
      with ATA were clinically euthyroid; 8 patients affected by RP did not show
      circulating ATA at the time of the study. The interest for the physician in this
      "syndromic" retinal distrophy reflects the need, emerging from our data, to test
      the thyroid function in the subjects with RP and in members of their families,
      since circulating ATA are considered a risk factor for the development of
      autoimmune hypothyroidism.

PMID- 8743284
TI  - Acute stimulation of the hypothalamic-pituitary-adrenal axis by IL-1 beta, TNF
      alpha and IL-6: a dose response study.
AB  - We investigated the effects of i.v. and intracerebroventricular (i.c.v)
      administration of increasing doses of recombinant human IL-1 beta, TNF alpha and
      IL-6 on plasma corticosterone (B) levels in rats. Rats were equipped with a
      jugular cannula for repeated blood sampling anda subgroup of rats also received
      an i.c.v implanted cannula. I.v. administration of IL-1 beta, TNF alpha or IL-6
      and i.c.v administration of IL-1 beta and IL-6 induced a significant dose
      dependent increase in plasma B levels, whereas i.c.v injection of TNF alpha in
      doses up to 1000 ng/rat was not effective. I.v. pretreatment of rats with anti
      CRH antiserum had no significant overall effect on the plasma B response to i.v.
      administered IL-1 beta (500 and 3000 ng/rat), whereas the plasma B response to
      i.v. TNF alpha or IL-6 administration (3000 ng/rat) were significantly reduced.
      I.v. pretreatment of the animals with recombinant human IL-1 receptor antagonist
      (IL-1ra) significantly blocked the plasma B response to i.v. treatment with IL-1
      beta, whereas the TNF alpha- and IL-6-induced increases in plasma B levels were
      not affected. Our data show that 1) i.v. administration of IL-beta, TNF alpha or
      IL-6 and i.c.v administration of IL-1 beta or IL-6 dose-dependently stimulate the
      HPA axis; 2) when given i.v. or i.c.v, IL-1 beta is more powerful than TNF alpha
      and IL-6 in activating the HPA axis; 3) endogenous CRH is involved in the
      activation of the HPA axis by acute i.v. administration of TNF alpha and IL-6. It
      is most likely that in case of i.v. treatment with IL-1 beta a CRH-independent
      mechanism is involved. This study provides no arguments for the involvement of
      endogenous IL-1 in TNF alpha- or IL-6-induced activation of the HPA axis.

PMID- 8743285
TI  - Expression of ICAM-1 in distant metastatic thyroid carcinoma.
AB  - Distant metastasis from follicular thyroid carcinoma developed in a 48-year-old
      woman 11 yr after the resection of the primary tumor. Distant metastasis
      consisted in invasion of the left infraspinatus muscle by malignant thyroid
      cells. After its surgical removal, in the following 6-8 months multiple
      metastasis to distant skeletal muscle and brain appeared, and despite
      chemotherapy and local radiotherapy, the patient finally died. Intercellular
      adhesion molecule-1 (ICAM-1), a single chain transmembrane glycoprotein, was
      detected on the surface of cells of the metastatic tissue. Although ICAM-1
      positive staining has been recently described in primary tumors such as papillary
      adenocarcinoma, and metastatic tumors from skin, brain, thymus, liver, adrenal
      gland and prostate, to our knowledge its expression on distant metastasis from
      thyroid carcinoma has not been previously reported.

PMID- 8743286
TI  - Bronchial carcinoid tumor presenting as a thyroid nodule: an unusual clinical
      manifestation.
AB  - Although rare, carcinoid tumors may present as thyroid metastatic nodules. We
      describe two patients with an undiagnosed bronchial carcinoid tumor, who
      presented as a thyroid nodule. Pathological examination of these nodules was
      diagnostic. Chemotherapy was indicated despite the dissemination of the tumors.
      The patients have an excellent quality of life. They are asymptomatic and alive,
      18 and 24 months after diagnosis, respectively. In one case, chemotherapy
      obtained an important reduction in the size of the tumoral lesions but the other
      case showed no regression. Octreotide (SMS 201-995) was used in the case with
      carcinoid syndrome, with an excellent response.

PMID- 8743288
TI  - Microprolactinomas: why requiem for surgery?

PMID- 8743287
TI  - Neuropeptide Y secretion from a human insulinoma.
AB  - Neuropeptide Y (NPY) is a 36 aminoacid peptide known to inhibit glucose
      stimulated insulin secretion. NPY has been shown to be synthesized and secreted
      by rat islets of Langerhans. More recently, we described the presence on NPY
      within human islets of Langerhans and in several pancreatic endocrine tumors. In
      this report, we describe the case of a patient presenting with an insulinoma who
      underwent the surgical resection of the tumor and was studied in vivo and in
      vitro for NPY production. Using a highly specific and sensitive two-site
      amplified enzyme-linked immunosorbent assay, we detected high plasma NPY levels
      in the patient prior to the surgical resection of the tumor which returned to
      normal after surgery. NPY was secreted from the tumor when kept in primary cell
      culture. Furthermore, immunohistochemistry of the insulinoma revealed the
      presence of NPY and its C-flanking peptide together with insulin, chromogranin
      and neuron specific enolase. It is concluded that elevated circulating NPY levels
      observed in this patient with an insulinoma reflected in vivo secretion by the
      tumor and it is hypothesized that NPY could potentially be used as an endocrine
      marker in patients with suspected insulinoma.

PMID- 8743289
TI  - Mapping of an autoreactive epitope within glutamate decarboxylase using a
      diabetes-associated human monoclonal autoantibody and an epitope cDNA library.
AB  - Glutamate decarboxylase (GAD65) is a major autoantigen in insulin-dependent
      diabetes (IDDM) and the neurological disorder Stiff-Man-Syndrome (SMS). We
      derived a human monoclonal autoantibody (MICA 2) from peripheral blood of a
      patient newly diagnosed with IDDM, which reacted with GAD65 in Western blots.
      This indicated that a linear epitope is recognized by MICA 2. Using an epitope
      cDNA library we mapped the MICA 2 epitope to a contiguous stretch of 26 amino
      acids (506-531) in the C-terminus of GAD65. Neither blocking experiments with
      synthetic peptides nor analysis of overlapping decapeptides expressed as fusion
      proteins allowed us to further narrow down the epitope to the typical size of
      linear epitopes of 6-8 amino acids. We suggest that a miniconformational epitope
      provided by amino acids 506-531 is recognized by MICA 2, which withstands SDS gel
      electrophoresis without destruction or partially refolds during the Western blot
      procedure. A sequence homology with human heat shock protein 60 (HSP60) maps to
      this region of GAD65 but no cross-reactivity of MICA 2 with HSP60 occurred. Our
      data demonstrate that reactivity of an antibody in Western blots does not
      necessarily define a classic linear epitope of 6-8 amino acids and describe a new
      autoreactive epitope in GAD65 different from those reported for sera from
      patients with SMS.

PMID- 8743290
TI  - Epitope mapping of new monoclonal antibodies recognizing distinct human FcRII
      (CD32) isoforms.
AB  - The class II Fc gamma receptors are widely distributed on cells of the immune
      system. Nevertheless, the exact cell type distribution of the FcRII isoforms is
      still unclear because of the lack of appropriate antibodies that discriminate
      between the various isoforms. In this study we describe the generation and
      characterization of three monoclonal antibodies (MAbs) raised against recombinant
      human FcRIIb2 as well as a synthetic peptide (amino acids 30-39) of this
      receptor. Analyses of the isoform specificity of these antibodies using ELISA and
      Western blots revealed that the MAbs II1A5 (mIgG1) and ID2.7 (mIgM) are pan FcRII
      antibodies recognizing all known FcRII isoforms. In contrast, the MAb II8D2
      (mIgG1) specifically reacts with FcRIIb but not with FcRIIa. The observed
      antibody reactivities could be confirmed by examination of the exact epitopes
      using overlapping 15-mer peptides spanning the entire FcRIIb2. So far these
      antibodies are the only ones described that detect FcRII in Western blots.
      Moreover, they can be used to analyze the cellular FcRII isoform distribution at
      the protein level, which was otherwise not possible.

PMID- 8743291
TI  - Structural diversity of monoclonal CD4 antibodies and their capacity to block the
      HIV gp120/CD4 interaction.
AB  - A number of monoclonal antibodies have been raised against CD4, the receptor on T
      cells for the HIV envelope glycoprotein gp120. In the present paper we describe
      biological activities and sequence analysis of seven CD4 MAb. Five of these MAb
      preparations compete with HIV/gp120 for CD4 binding. The sequences of the
      variable regions for these MAb were determined in order to ascertain any
      correlation with selective V gene usage. A relationship was found between the
      expressed variable region genes and the CD4 recognition pattern. The VH genes
      that are used can be subdivided into two major groups expressing either a VH gene
      belonging to the J558 family or to the VGam family. The usage of the VL genes
      varies, indicating that the epitope specificity is predominantly determined by
      the rearranged VH genes. The distinct cross-reactivity pattern of these MAb also
      correlates with their capacity to block binding of recombinant gp120 to CD4 in
      vitro. Although five of these MAb were able to block gp120 binding none of the
      CDR sequences shows a relevant homology to the gp120 sequence. This indicates a
      steric hinderence mechanism for blocking gp120 binding and not a direct
      interaction with the receptor binding site on CD4. The data also confirm the
      failure of these MAb as a potential target for receptor mimicry.

PMID- 8743292
TI  - VLA-beta 1 integrin subunit-specific monoclonal antibodies MB1.1 and MB1.2:
      binding to epitopes not dependent on thymocyte development or regulated by
      phorbol ester and divalent cations.
AB  - We report here the isolation of two new monoclonal antibodies (MB1.1 and MB1.2)
      against mouse VLA-beta 1 integrin subunit. Characterization by flow cytometry
      demonstrated binding of MB1.1 and MB1.2 to freshly isolated thymocytes, primary
      bone marrow mast cell lines, as well as cell lines of distinct lineage each
      expressing different combination of VLA integrins. The specificity of MB1.1 and
      MB1.2 was determined by (1) their binding to antigen with M(r) about 120 kDa, and
      (2) the ability of antiserum against the carboxyl terminal of VLA-beta 1 subunit
      to deplete antigens for MB1.1 and MB1.2 in sequential immunoprecipitation
      experiments. The epitopes for MB1.1 and MB1.2 were in close proximity to each
      other since preincubation of cells with one MAb inhibited the binding of the
      other. However, MB1.1 and MB1.2 differed in their affinity for the beta 1
      subunit. In addition, neither MAbs had any effect on cell adhesion to matrix
      proteins indicating that the epitopes involved are distant from VLA integrin
      ligand-binding sites. MB1.1 and MB1.2 appear to differ from the two MAbs so far
      reported against mouse VLA-beta 1 subunit, KMI6 and 9EG7. Thus, the epitopes for
      MB1.1 and MB1.2 were readily detectable on unfractionated thymocytes whereas KMI6
      has been reported to bind only a fraction of CD4-8- and CD4-8+ thymocytes.
      Phorbol ester and Mn2+, which have been shown to regulate the binding of 9EG7,
      had no effect on MB1.1 and MB1.2 binding to VLA-beta 1 integrin subunit.

PMID- 8743293
TI  - Monoclonal antibody to VIP: production, characterization, immunoneutralizing
      activity, and usefulness in cytochemical staining.
AB  - A very stable cell line has been generated that produces monoclonal antibody to
      VIP designated as CURE.V55. This hybridoma was produced by fusion of spleen cells
      from an immunized Robertsonian mouse containing the translocated 8.12 chromosome
      with FOX-NY myeloma cells that are APRT deficient. VIP monoclonal antibody
      producing cell line #55 was selected by limiting dilutions using thymocytes as
      feeder layers. Ascites fluid containing high concentration of VIP monoclonal
      antibody was produced from pristane-primed BALB/c mice. Ascites fluid contained
      approximately 20 mg/ml IgG and bound 50% of 2 fmol 125I-VIP at a final dilution
      of 1:50,000. Binding of this IgG1 antibody was inhibited by 50% at 5 nM
      concentration of either VIP 1-28 or VIP 7-28. Protein-A purified IgG of this
      antibody, used in a concentration of 30 mg/kg per rat (IV), completely reversed
      the inhibitory effect of gastric corpus contractions induced by intravenous
      injection of VIP (10 nmol/kg) in sodium pentothal-anesthetized rats. A control
      anti-keyhole limpet hemocyanin monoclonal antibody did not alter the stimulatory
      effect of VIP on gastric corpus contractions. Immunohistochemistry showed that
      this VIP monoclonal antibody stains neurons, and nerve fibers in human and rat
      gallbladder and the sphincter of Oddi as previously described with our polyclonal
      antiserum.

PMID- 8743294
TI  - Tumor antigen expression in compound dysplastic nevi and superficial spreading
      melanoma defined by a panel of nevomelanoma monoclonal antibodies.
AB  - Studies of antigen expression in dysplastic nevi have been limited to some extent
      by difficulties in obtaining frozen nevi with which to react monoclonal
      antibodies. Accordingly, we obtained a panel of antibodies that binds to antigens
      preserved in paraffin-embedded tissue. This panel of monoclonal antibodies,
      raised against nevomelanoma antigens, was used on 26 dysplastic compound nevi and
      additionally on 14 invasive superficial spreading melanomas. Among the dysplastic
      nevi, two basic dermal staining patterns emerged. One pattern designated "Type 1"
      shows a histologically well-developed dermal component that tends to be
      antigenically well stratified, with the cells in the upper dermis expressing the
      most antigen, and gradual loss of antigenicity in the lower dermis as maturation
      of nevic cells occurs. A second ("Type 2") pattern was seen in which nevic cells
      tended to remain in the upper dermis, with less downgrowth, and to express
      antigen in a diffuse or patchy, but nonstratified distribution. Some differential
      distribution of the antigens was noted, with antibodies 404-101, HMB-45, and ME
      109 binding to the activated junctional zone, but showing lower binding affinity
      within the dermis. ME 491, NKI-C3, and 506 bind to antigens abundant in the
      junctional zone as well as the dermis. The antibody ME 67-6 binds to both
      junction and dermis, but is more useful for delineation of antigenic
      stratification and presence of abnormal "clones."

PMID- 8743295
TI  - HLA-B-restricted, CD8+ cytolytic human T cell clones derived from a melanoma
      invaded lymph node.
AB  - We have reported that medium containing recombinant human IL-1 (rIL-1), rIL-2,
      rIL-4, and rIL-6 (MB-1,2,4,6 medium) efficiently expanded autologous tumor
      specific CTLs in vitro. For further examination of the CTLs cultured in MB
      1,2,4,6, the therapeutic activity on tumor growth inhibition in vivo and
      established CTL clones were studied. In vivo therapy with the CTLs in combination
      with rIL-2 was highly effective. To investigate CTL clones, 19 CD8+ T cell clones
      were obtained by limiting dilution method, each clone retained autologous
      melanoma-specific, HLA-class I-restricted cytolytic activity. Four T cell clones
      were analyzed in detail. These T cell clones displayed a CD3+, CD4-, CD8+, CD11b
      , CD16-, CD56-, CD45RA-, TcR alpha/beta + phenotype and monoclonal antibodies to
      HLA class I, CD3, and CD8 antigens inhibited their cytolytic activity. Moreover,
      these CTL clones recognize one of common melanoma antigens associated with HLA-B
      (B49). Analysis of the effect of different cytokines on the proliferation and
      cytotoxicity of cloned CTL revealed the highest growth rate in MB-1,2,4,6 but no
      dependence on particular cytokine combinations for autologous tumor-specific
      cytolytic activity. These results suggest (1) the usefulness of MB-1,2,4,6 medium
      in expanding autologous tumor-specific CTLs, which can be used in adoptive
      immunotherapy, (2) HLA-B molecules can present one of common melanoma antigens,
      and (3) the independence of CTLs from any cytokine combination once they become
      target-specific.

PMID- 8743296
TI  - Cloning and expression of cDNAs encoding the variable domains of the antibreast
      carcinoma antibody Mc5.
AB  - Mc5, a murine monoclonal antibody that binds to human breast epithelial mucin
      (BEM), has been shown to be a promising reagent in the diagnosis of breast
      cancer. We have cloned cDNAs encoding both variable regions of Mc5 (VL and VH) as
      well as the CL and CH1 constant regions. Mc5 is an IgG1, kappa antibody. We have
      constructed an IgG1, kappa human/mouse chimeric antibody (by inserting the murine
      VH and VL-encoding cDNAs into plasmids encoding human constant domains), and
      expressed it in SP2/0-Ag14 mouse myeloma cells. The affinity of chimeric Mc5
      (chMc5) for BEM is 4.4 x 10(8) M-1. Mc5 binds BEM with an affinity constant of
      2.8 x 10(8) M-1. Purified chMc5 and purified Mc5 gave similar competition curves
      when tested against either 125I-labeled Mc5 or 125I-labeled chMc5 for binding to
      BEM in a competition radioimmunodetection format. Additionally, chMc5 used in
      breast carcinoma tissue staining stained as well as the original Mc5.

PMID- 8743298
TI  - Measuring activities of daily living among haemophiliacs.
AB  - To explore the activities of daily living (ADL) status and/or changes in
      functional limitations among haemophiliacs, 97 patients were studied
      longitudinally using a 41-item checklist. The total number of data items was 239
      with repeated inquiries. Hierarchical factor analyses yielded a clear separation
      of items into five factors by the analogous trunk and limb motion, and the
      existence of one higher-order factor which indicated that the items measured the
      same underlying concept. Analyses of ratings showed that in haemophiliacs full
      flexion of the lower limbs was easily limited, and this deterioration was
      difficult to prevent. The functional limitation level differed significantly by
      age group, but some patients showed a slight improvement in a follow-up
      observation. The ADL of haemophiliacs should be explored separately for trunk and
      limb motion, not for the traditional categories.

PMID- 8743297
TI  - Epitopic characterization of neuropeptide Y (NPY) by alanine-scanning
      mutagenesis.
AB  - Characterization of the epitopic structures of neuropeptide Y (NPY) has been
      studied by alanine-scanning mutagenesis, based on our previous investigation of a
      panel of six murine anti-NPY IgM monoclonal antibodies. To evaluate the
      structural requirement for these anti-NPY IgM antibodies, recognition variants of
      the native sequences of the NPY fragment (19-36) were prepared by single alanine
      substitutions in residues 22 and 25-36. Their binding to these antibodies was
      examined by competitive inhibition assays. The results demonstrated that the
      epitopic structures are largely confined to residues 25-36 of NPY and the C
      terminal residues of NPY are essential for these anti-NPY IgM antibodies
      recognition. It emphasizes the notion that even small regions of a protein
      consisting of as few as 15 residues (22-36) can exhibit multiple epitopic
      structures. In several anti-NPY IgM antibodies, pairs of residues on opposite
      faces of the alpha-helix interact with the antibody site, which indicates that
      the antibody site consists either of a cavity or a deep groove either of which
      encompasses the alpha-helical segment sufficiently to allow simultaneous contact
      with most of the residues of this segment.

PMID- 8743299
TI  - Factors related to successful rehabilitation after hip fracture: a case-control
      study.
AB  - A case-control study was performed to evaluate factors associated with successful
      rehabilitation in elderly patients who sustained hip fractures. All 170 patients
      with fractured hips hospitalized in the geriatrics ward of the Soroka Medical
      Center in Beer-Sheva, Israel between 1987 and 1991 were studied. Success of
      rehabilitation was determined by staff evaluation of the patient's ability to
      walk and perform activities of daily living. The independent variables, including
      sociodemographic and medical variables, and mental and functional assessments,
      were assessed by chart reviews, staff evaluation and mental tests. One-hundred
      and twenty-nine patients (75.9%) were successfully rehabilitated. A normal mental
      state (p < 0.0001), female gender (p < 0.02) and absence of diabetes mellitus (p
      < 0.008) were associated significantly with successful rehabilitation.

PMID- 8743300
TI  - A follow-up study of patients hospitalized after minor head injury.
AB  - Minor head injury accounts for 95% of all head injury. In this study 62 patients,
      hospitalized after minor head injury, were assessed within 48 h, and invited to
      attend for review and retesting 3 months later. Thirty-five patients were
      followed up in this way and 11 more were interviewed over the telephone. There
      was significant improvement on all psychometric tests between initial evaluation
      and follow-up. Between 51% and 86% reported troublesome late post-concussional
      symptoms, of which headaches and tiredness were the most frequently reported
      symptoms. Length of post-traumatic amnesia (PTA) was related to severity of
      symptoms. Clinical levels of anxiety and stress were noted in approximately one
      third of the whole group; 95% of the group had returned to work by 3 months with
      a mean absence rate of 9.4 days. The therapeutic implications of these results
      are discussed.

PMID- 8743301
TI  - Frenchay Aphasia Screening Test: validity and comparability.
AB  - The Frenchay Aphasia Screening Test1 is a reliable test which can be used by non
      specialists to discriminate between aphasia and normal language. Preliminary
      studies have shown good test-retest reliability, and the test itself is quick and
      simple to use. The present investigation examines the validity of the test by
      comparing the results of this test with those on more structured, detailed and
      frequently used assessments of aphasia -the Minnesota Test for Differential
      Diagnosis of Aphasia (MTDDA) and general performance in communication as
      reflected by the Functional Communication Profile. The results demonstrate a
      positive correlation between the tests, and this allows confidence in the use of
      this test by non-specialists as a screening instrument.

PMID- 8743302
TI  - Impact of fibromyalgia on everyday life: a study of women in the USA and Sweden.
AB  - The study investigated how 39 women with fibromyalgia (FM), living in two
      countries (USA or Sweden), report the consequences of fibromyalgia on everyday
      life activities. Data were collected using questionnaires, diaries and
      interviews. The result showed that the impact on everyday life was considerable.
      The majority of the women experienced pain and fatigue for more than 90% of their
      time awake. There were no significant differences between the national groups in
      time use, problems with everyday activities, or quality of life. Overall, the
      differences between individuals were greater than between the national groups.
      The majority of the employed patients in the Swedish group had reduced their
      working time, while the employed patients in the USA group worked mainly full
      time. Patients who were able to reduce their working hours to fit their perceived
      capacity were less exhausted during their leisure, and reported higher
      satisfaction with daily activities.

PMID- 8743303
TI  - Correlates of fatigue in HIV infection prior to AIDS: a pilot study.
AB  - Fatigue is widely recognized as a significant source of morbidity in persons with
      human immunodeficiency virus (HIV) infection, yet there are few data examining
      fatigue in this population. We present pilot data assessing the relationship
      between fatigue and various physical and psychosocial measures in 20 men with HIV
      infection prior to the clinical development of acquired immunodeficiency syndrome
      (AIDS). Fatigue was measured by a visual analogue scale (VAS) and the Fatigue
      Assessment Inventory (FAI). No statistically significant associations were found
      between fatigue measures and physical parameters including haemoglobin,
      haematocrit, albumin, total protein, and physical dimension score of the Sickness
      Impact Profile (SIP). The FAI correlated well with Beck's Depression Inventory
      and SIP-Psychosocial Dimension (r = 0.72 and 0.81, respectively; p < 0.001.) Both
      the FAI and VAS held moderate associations with the total SIP score. The SIP
      profile was similar to that observed in a sample of persons with chronic fatigue
      but without HIV infection, reported previously. Although the sample size is
      small, our data suggest a stronger association with psychosocial, rather than
      physical, parameters among persons with HIV infection and fatigue. The
      implications for clinical management and further research are discussed.

PMID- 8743304
TI  - Appreciation of community-based rehabilitation by caregivers of children with a
      disability.
AB  - Evaluations of community-based rehabilitation (CBR) programmes generally focus on
      quantitative data. To gain insight into the determinants of the outcomes, process
      oriented data are needed. From the literature six variables have been identified
      that possibly correlate with the evaluation of CBR by caregivers of children with
      a disability. These variables are: (1) traditional beliefs, (2) impact of a child
      with a disability on the caregiver, (3) community involvement, (4) perceived
      ability to teach the child, (5) attitude towards various health services, and (6)
      expectations for the future of a disabled child. The study was done in the CBR
      projects in Zimbabwe. Seventy-five caregivers were interviewed. Background,
      perceived abilities to teach and expectations of the caregivers were very
      different. This study revealed a significant correlation between the appreciation
      of CBR and the attitude towards various health services, and between the
      perceived ability to teach and the expectations for the future of the child.

PMID- 8743305
TI  - A creative art centre for adults with developmental disabilities.
AB  - An art centre for adults with developmental disabilities is described, and its
      origins and dissemination are presented. Differences between such art centres and
      more traditional work-oriented programmes for people with developmental
      disabilities are indicated. The number of similar art centres for this population
      has increased substantially during the past 20 years.

PMID- 8743306
TI  - Cognitive rehabilitation following anterior communicating artery aneurysm
      bleeding: a case report.
AB  - The present case report documents the successful rehabilitation of a severely
      amnesic anterior communicating artery aneurysm patient. The patient was able to
      return to his premorbid high-level occupation after significant improvement in
      executive functioning, moderate improvement in visual memory, modest improvement
      in immediate verbal memory, and minimal improvement in delayed verbal memory. An
      interdisciplinary approach to rehabilitation was utilized in conjunction with
      empirically based intervention strategies. The implications of improved executive
      functions versus memory functions for successful rehabilitation are discussed.

PMID- 8743307
TI  - Affinity maturation of phage-displayed peptide ligands.

PMID- 8743308
TI  - Selection for protease inhibitors using bacteriophage display.

PMID- 8743309
TI  - Phage display of proteases and macromolecular inhibitors.
AB  - We describe methods for displaying the protease trypsin and the macromolecular
      protease inhibitor ecotin on the surface of filamentous phage. Our strategy for
      selecting variant ecotins against target proteases is also described. We believe
      that the two proteins that have been displayed serve as ideal models for studying
      molecular recognition in detail. The ability to search efficiently through a
      large number of variant proteins for desired properties using phage display
      technology and the in vitro selection methods described opens a new avenue for
      studying protein-ligand interactions, as well as creating proteins with novel
      functions.

PMID- 8743310
TI  - Affinity maturation of proteins displayed on surface of M13 bacteriophage as
      major coat protein fusions.
AB  - This chapter described the preparation and fractionation of libraries of M13
      phage displaying proteins as fusions to the major coat protein. High titer
      (10(13) pfu/ml) phage libraries can readily be generated using a single vector
      and the level of display surpasses that of gene III fusion phage. Since the
      synthetic VIII fusion gene can be customized, this system should provide the
      flexibility required to construct phage libraries displaying a variety of
      different peptides and proteins and to select variants possessing the highest
      affinity for target molecules of a diverse chemical nature.

PMID- 8743311
TI  - Screening of phage antibody libraries.

PMID- 8743312
TI  - Immunization with phage-displayed mimotopes.

PMID- 8743313
TI  - Phage-displayed peptides as tools for characterization of human sera.

PMID- 8743314
TI  - Phage display methods for selecting zinc finger proteins with novel DNA-binding
      specificities.

PMID- 8743315
TI  - In vitro genetic analysis of RNA-binding proteins using phage display libraries.

PMID- 8743316
TI  - Screening of peptide libraries linked to lac repressor.

PMID- 8743317
TI  - Cell-free synthesis of peptide libraries displayed on polysomes.

PMID- 8743318
TI  - One bead-one compound combinatorial peptide library: different types of
      screening.

PMID- 8743319
TI  - Generation and use of nonsupport-bound peptide and peptidomimetic combinatorial
      libraries.

PMID- 8743320
TI  - Combinatorial chemistry: a liquid-phase approach.

PMID- 8743321
TI  - Preparation of equimolar mixtures of peptides by adjustment of activated amino
      acid concentrations.

PMID- 8743322
TI  - Encoded combinatorial chemistry: binary coding using chemically robust secondary
      amine tags.

PMID- 8743323
TI  - A SELEX primer.

PMID- 8743324
TI  - Identifying consensus patterns and secondary structure in SELEX sequence sets.

PMID- 8743325
TI  - Affinity selection-amplification from randomized ribooligonucleotide pools.

PMID- 8743326
TI  - In vitro selection of nucleic acid aptamers that bind proteins.

PMID- 8743327
TI  - Randomization and selection of RNA to identify targets for RRM RNA-binding
      proteins and antibodies.

PMID- 8743328
TI  - Selection of aminoacylated tRNAs from RNA libraries having randomized acceptor
      stem sequences: using old dogs to perform new tricks.

PMID- 8743329
TI  - In vitro evolution of randomized ribozymes.

PMID- 8743330
TI  - Peptide nucleic acids: a new dimension to peptide libraries and aptamers.

PMID- 8743331
TI  - Synthesis of N-substituted glycine peptoid libraries.

PMID- 8743332
TI  - Synthesis and evaluation of 1,4-benzodiazepine libraries.

PMID- 8743333
TI  - A size standard for pharmacokinetics.

PMID- 8743335
TI  - Clinical pharmacokinetics of metformin.
AB  - The biguanide metformin (dimethylbiguanide) is an oral antihyperglycaemic agent
      widely used in the management of non-insulin-dependent diabetes mellitus (NIDDM).
      Considerable renewal of interest in this drug has been observed in recent years.
      Metformin can be determined in biological fluids by various methods, mainly using
      high performance liquid chromatography, which allows pharmacokinetic studies in
      healthy volunteers and diabetic patients. Metformin disposition is apparently
      unaffected by the presence of diabetes and only slightly affected by the use of
      different oral formulations. Metformin has an absolute oral bioavailability of 40
      to 60%, and gastrointestinal absorption is apparently complete within 6 hours of
      ingestion. An inverse relationship was observed between the dose ingested and the
      relative absorption with therapeutic doses ranging from 0.5 to 1.5 g, suggesting
      the involvement of an active, saturable absorption process. Metformin is rapidly
      distributed following absorption and does not bind to plasma proteins. No
      metabolites or conjugates of metformin have been identified. The absence of liver
      metabolism clearly differentiates the pharmacokinetics of metformin from that of
      other biguanides, such as phenformin. Metformin undergoes renal excretion and has
      a mean plasma elimination half-life after oral administration of between 4.0 and
      8.7 hours. This elimination is prolonged in patients with renal impairment and
      correlates with creatinine clearance. There are only scarce data on the
      relationship between plasma metformin concentrations and metabolic effects.
      Therapeutic levels may be 0.5 to 1.0 mg/L in the fasting state and 1 to 2 mg/L
      after a meal, but monitoring has little clinical value except when lactic
      acidosis is suspected or present. Indeed, when lactic acidosis occurs in
      metformin-treated patients, early determination of the metformin plasma
      concentration appears to be the best criterion for assessing the involvement of
      the drug in this acute condition. After confirmation of the diagnosis, treatment
      should rapidly involve forced diuresis or haemodialysis, both of which favour
      rapid elimination of the drug. Although serious, lactic acidosis due to metformin
      is rare and may be minimised by strict adherence to prescribing guidelines and
      contraindications, particularly the presence of renal failure. Finally, only very
      few drug interactions have been described with metformin in healthy volunteers.
      Plasma levels may be reduced by guar gum and alpha-glucosidase inhibitors and
      increased by cimetidine, but no data are yet available in the diabetic
      population.

PMID- 8743334
TI  - Clinical pharmacokinetics of therapeutic bile acids.
AB  - The pharmacokinetics of chenodeoxycholic and ursodeoxycholic acids are reviewed
      in this article. Chenodeoxycholic acid is well absorbed by the intestine, whereas
      the absorption of ursodeoxycholic acid is incomplete. They are extracted
      efficiently by the liver, conjugated with glycerine and taurine, secreted in
      bile, and then undergo enterohepatic circulation with the endogenous bile acids.
      Therapeutic bile acids are metabolised by intestinal bacteria to lithocholic acid
      which is mainly excreted with faeces. Since the large majority of bile acid is
      confined within the enterohepatic circulation (resulting in low serum
      concentrations) their volume of distribution is relatively high. Despite the high
      hepatic extraction, the clearance of therapeutic bile acids is relatively low
      because of the highly efficient enterohepatic recirculation. Elimination of
      therapeutic bile acids mainly occurs in the faeces either unmodified or after
      biotransformation. At present the main clinical indication for therapeutic bile
      acids is ursodeoxycholic acid treatment for chronic cholestatic liver disease. In
      these patients, ursodeoxycholic acid is efficiently absorbed but its hepatic
      uptake and biliary secretion are impaired, thus leading to reduced biliary
      enrichment and high serum concentrations of this exogenous bile acid. In patients
      with cystic fibrosis-associated liver disease, bile acid malabsorption also
      occurs, thus indicating the need for higher dosages. The volume of distribution
      and clearance of ursodeoxycholic acid reduced in the presence of liver disease.
      Also in this case, elimination mainly occurs with the faeces but, in the presence
      of severe cholestasis, renal clearance may become relevant. Sulphation or
      conjugation with glucose and N-acetylglucosamine facilitate urinary excretion.

PMID- 8743336
TI  - Clinical pharmacokinetics of molsidomine.
AB  - Molsidomine is a prodrug for the formation of nitric oxide (NO). Its
      pharmacokinetics are characterised by rapid absorption and hydrolysis, taking a
      short time to achieve maximal systemic concentrations of both the parent compound
      and its active metabolite, SIN-1. The time to peak plasma drug concentration
      (tmax) is 1 to 2 hours. The bioavailability of the parent compound after oral
      administration in tablet form is 44 to 59%, but further metabolism to release NO
      and form polar metabolites is rapid; the half-life (t-1/2) of SIN-1 is 1 to 2
      hours. Urinary excretion accounts for more than 90% of the part of the
      administered dose of molsidomine which is not excreted unchanged. Protein binding
      of the parent compound is very low (3 to 11%) and its volume of distribution (Vd)
      corresponds to the range of bodyweight. Single-dose studies (1, 2 and 4 mg) have
      revealed linear pharmacokinetics, and multiple dose studies in healthy
      individuals (2 mg 3 times daily for 7 days) and coronary artery disease (CAD)
      patients (4 mg 4 times daily for 4 weeks) do not show any accumulation of the
      drug. A study in young and elderly individuals indicated that the first-pass
      effect is decreased and t-1/2 prolonged with age, resulting in an increased area
      under the concentration-time curve (AUC) of molsidomine and SIN-1. In patients
      with liver disease and congestive heart failure similar changes were observed,
      but much less so in patients with CAD. Clearance was also impaired in patients
      with liver disease, but the pharmacokinetics of molsidomine were not markedly
      altered by impaired renal function. In general, due to a large therapeutic dose
      range, dosage adjustments are not required on the basis of clinical experience.
      In certain patients a lower starting dose may be recommended, such as in those
      with impaired liver or kidney function, in congestive heart failure or in the
      presence of concomitant treatment with other vasoactive compounds. A linear dose
      effect relationship is observed with counterclockwise hysteresis, i.e. a greater
      effect associated with the decrease of plasma concentrations than during their
      increase, which may be at least partly due to the metabolic delay in the
      formation of NO from SIN-1. Accordingly, the duration of action of molsidomine is
      longer than would be expected on the basis of the elimination half-life. The
      pharmacokinetics of molsidomine support the recommended dosages for use in angina
      pectoris.

PMID- 8743338
TI  - Acoustic neuroma update.
AB  - We have described refinements and alternative techniques in the management of
      acoustic neuromas. The outcome for patients with both unilateral and bilateral
      tumors continues to improve.

PMID- 8743337
TI  - Drug interactions with antiviral drugs.
AB  - Antiviral drug interactions are a particular problem among immuno-compromised
      patients because these patients are often receiving multiple different drugs,
      i.e. antiretroviral drugs and drugs effective against herpesvirus. The
      combination of zidovudine and other antiretroviral drugs with different adverse
      event profiles, such as didanosine, zalcitabine and lamivudine, appears to be
      well tolerated and no relevant pharmacokinetic interactions have been detected.
      The adverse effects of didanosine and zalcitabine (i.e. peripheral neuropathy and
      pancreatitis) should be taken into account when administering these drugs with
      other drugs with the same tolerability profile. Coadministration of zidovudine
      and ganciclovir should be avoided because of the high rate of haematological
      intolerance. In contrast, zidovudine and foscarnet have synergistic effect and no
      pharmacokinetic interaction has been detected. No major change in zidovudine
      pharmacokinetics was seen when the drug was combined with aciclovir, famciclovir
      or interferons. However, concomitant use of zidovudine and ribavirin is not
      advised. Although no pharmacokinetic interaction was documented when didanosine
      was first administered with intravenous ganciclovir, recent studies have shown
      that concentration of didanosine are increased by 50% or more when coadministered
      with intravenous or oral ganciclovir. The mechanism of this interaction has not
      been elucidated. Lack of pharmacokinetic interaction was demonstrated between
      foscarnet and didanosine or ganciclovir. Clinical trials have shown that
      zidovudine can be administered safely with paracetamol (acetaminophen),
      nonsteroidal anti-inflammatory drugs, oxazepam or codeine. Inhibition of
      zidovudine glucuronidation has been demonstrated with fluconazole, atovaquone,
      valproic acid (valproate sodium), methadone, probenecid and inosine pranobex;
      however, the clinical consequences of this have not been fully investigated. No
      interaction has been demonstrated with didanosine per se but care should be taken
      of interaction with the high pH buffer included in the tablet formulation. Drugs
      that need an acidic pH for absorption (ketoconazole, itraconazole but not
      fluconazole, dapsone, pyrimethamine) or those that can be chelated by the ions of
      the buffer (quinolones and tetracyclines) should be administered 2 hours before
      or 6 hours after didanosine. Very few interaction studies have been undertaken
      with other antiviral drugs. Coadministration of zalcitabine with the antacid
      'Maalox' results in a reduction of its absorption. Dapsone does not influence the
      disposition of zalcitabine. Cotrimoxazole (trimethoprim-sulfamethoxazole) causes
      an increase in lamivudine concentrations by 43%. Saquinavir, delavirdine and
      atevirdine appeared to be metabolised by cytochrome P450 and interactions with
      enzyme inducers or inhibitors could be anticipated. Some studies showed that
      interferons can reduce drug metabolism but only a few studies have evaluated the
      pathways involved. Further studies are required to better understand the clinical
      consequences of drug interactions with antiviral drugs. Drug-drug interactions
      should be considered in addition to individual drug clinical benefits and safety
      profiles.

PMID- 8743340
TI  - Pediatric otology.

PMID- 8743339
TI  - Sudden sensorineural hearing loss.
AB  - Approximately 4000 new cases of sudden hearing loss (SHL) occur annually in the
      United States, and 15,000 annually worldwide, accounting for approximately 1% of
      all cases of SHL. Although prevalence studies do not necessarily distinguish
      between idiopathic and acquired SHL, most cases of spontaneous SHL have no
      identifiable cause. In this article, the authors assess the cause, history,
      diagnosis, and treatment of SHL.

PMID- 8743341
TI  - Molecular genetics of deafness.
AB  - Significant progress has been made in the identification of genes responsible for
      nonsyndromic and syndromic HHI. The rapid pace of scientific discovery in the
      area of genetics of deafness will undoubtedly continue and provide novel insights
      into the mechanism of hearing.

PMID- 8743342
TI  - Eustachian tube dysfunction.
AB  - There are several types of eustachian tube dysfunction, including obstruction and
      abnormal patency. This article presents an update on several selected areas of
      eustachian tube function and dysfunction, including surfactants, cleft palate,
      tympanic membrane atelectasis, abnormal eustachian tube patency, and long-term
      middle ear ventilation.

PMID- 8743343
TI  - Update on facial nerve disorders.
AB  - Many issues involving the diagnosis and treatment of facial nerve disorders
      continue to engender controversy and debate. This article examines the theory
      that Bell's palsy is a herpes simplex neuritis and proposes facial nerve
      decompression for recurrent palsies. The contemporary management of herpes zoster
      oticus, temporal bone fractures, otogenic facial paralysis, and hemifacial spasm
      is reviewed.

PMID- 8743344
TI  - Update on tinnitus.
AB  - The study of a disorder such as tinnitus is fraught with difficulties. Tinnitus,
      like pain, is a subjective symptom. The problem is compounded because several
      different mechanisms must operate to cause the persistent sensation of tinnitus.
      Therefore, it is difficult to measure objectively any improvements in the
      condition. For example, it has been reported previously that sectioning the
      eighth cranial nerve does not abolish tinnitus in a majority of patients;
      therefore, central mechanisms must act to preserve the tinnitus. Finally, we know
      that tinnitus can occur in a host of conditions other than ototoxicity, aging,
      and noise exposure. Other conditions that may produce tinnitus are migraine
      headache with auditory aura, temporal lobe seizures, and head injuries.
      Therefore, it is naive to conceptualize that tinnitus is a disorder with a
      unitary origin and a unitary "cure".

PMID- 8743345
TI  - Update on skull base surgery.
AB  - The field of skull base surgery has changed significantly during the past decade.
      Various surgical approaches have been developed, which when used alone or in
      combination provide optimal exposure for the resection of a given lesion with
      minimal morbidity. This recent evolution in the field of skull base surgery has
      allowed the surgical management of larger lesions in previously inaccessible
      locations. Furthermore, techniques in the preoperative, intraoperative, and
      postoperative management of the intrapetrous internal carotid artery have
      circumvented many prior limitations of cranial base resections. The goals of this
      article are to provide an overview of the postlateral skull base approaches in
      use today, discuss the regions of the skull base that are accessible, and
      describe the state of the art in management of the intrapetrous internal carotid
      artery.

PMID- 8743346
TI  - Medicolegal aspects of neurotology.
AB  - In their professional capacity, physicians interact with the legal profession in
      a variety of ways. The interaction occurs most often in the situation where an
      individual suffering from a bodily injury seeks the recovery of monetary benefits
      through the legal system. This article reviews the manner in which physicians are
      contacted by attorneys in connection with workers' compensation cases and civil
      tort cases. It will also set forth various definitions of disability and contrast
      those definitions with the concept of impairment as that term is used in the
      medical profession. Suggestions for patient evaluation and a summary of the legal
      basis for the recovery of benefits are also presented.

PMID- 8743347
TI  - Future directions in otology and neurotology.

PMID- 8743348
TI  - Differential decondensation of class I (rat) and class II (mouse) spermatozoa
      nuclei by physiological concentrations of heparin and glutathione.
AB  - The kinetics of sperm nuclear decondensation induced by the action of
      physiological concentrations of heparin and glutathione was studied by comparing
      two rodents: the rat, with very stable protamine P1 containing chromatin (class I
      nuclei), and the mouse, with protamine P1 and protamine P2 (class II nuclei).
      Sperm suspensions were incubated at different temperatures (37, 40, 43, and 46
      degrees C) in media while keeping a constant concentration of either heparin or
      GSH and increasing concentrations of the other reagent. Spermatozoa nuclei
      without any treatment incubated for 72 h appear densely condensed. Swelling of
      mouse spermatozoa nuclei was observed after 30 min of incubation in the presence
      of efficient concentrations of heparin-GSH. The extent of this time lag was
      significantly reduced at higher temperatures. This behavior was also observable
      in the rat, but required time lags of 3-4 h. Electron microscopy observations
      showed that the pattern of nuclear decondensation was different in both animal
      species. Mice sperm nuclei initiates its decompaction by the peripheral regions
      and this behavior remains until late stages of decondensation. On the contrary,
      rat spermatozoa nuclei decondense initially at the central part of the nuclei
      while the periphery remains condensed, showing numerous residues of densely
      packed chromatin. In both cases, the chromatin is organized into "hub-like"
      nuclear bodies joined by a network of chromatin fibers.

PMID- 8743349
TI  - In vitro fertilization: increased VLA (very late antigen) integrins and
      fibronectin after acrosome reaction.
AB  - The pattern of detectable adhesion molecules (AM) on human ejaculated spermatozoa
      used for in vitro fertilization (IVF) of human oocytes was evaluated. The
      percentage of spermatozoa with the alpha chains 3, 4, 5, and 6 of the integrins
      (also called very late antigens, VLA alpha 3, 4, 5, 6), the alpha V and the beta
      3 chains, as well as the matrix proteins laminin and fibronectin, were determined
      by flow cytometry using monoclonal antibodies against integrins and matrix
      proteins before and after the acrosome reaction. This reaction was induced by the
      low-temperature method according to P. Sanchez, E. Topfer-Petersen, R. J. Aitken,
      and W. B. Schill (1991, Andrologia 23:197-203) and monitored by the binding of
      FITC-conjugated Pisum sativum agglutinin. Twenty-three of 34 investigated semen
      samples fertilized at least one oocyte (fertile group) and 11 samples did not
      induce a pronucleus formation or cleavage of an oocyte (infertile group).
      Significant differences in the classical semen parameters between both semen
      sample groups could be shown only for the percentage of progressively motile
      spermatozoa (p = .046, U test). The spermatozoa of the fertile group showed a
      significantly higher expression of VLA alpha 3 (p = .045) and fibronectin (p =
      .048). Additionally, after the loss of the acrosome a significantly higher
      expression of alpha 4, alpha 5, and alpha 6 chains of integrins (p < .05) was
      detected in the fertile semen group. In contrast, the inducibility of the
      acrosome reaction differed only to a nonsignificant extent (p = .094). These data
      suggest that spermatozoa showing a higher expression of the alpha chains of the
      integrins after the acrosome reaction have a better fertilization rate in vitro.

PMID- 8743350
TI  - Lectin-binding sites on human sperm during acrosome reaction: modifications
      judged by electron microscopy/flow cytometry.
AB  - Biochemical surface modifications occur during the capacitation and acrosome
      reaction of human sperm and among those, variations in the expression of
      carbohydrates moieties. A sequential study was performed with electronic
      microscopy and flow cytometry techniques, where the binding of 4 lectins was
      assessed on normal human sperm samples during in vitro induction of the acrosome
      reaction with calcium ionophore A-23187. Triticum vulgaris agglutinin (WGA) was
      shown to bind strongly the whole surface of sperm before induction of the
      acrosome reaction, and in lesser amounts after incubation with calcium ionophore.
      Arachis hypogea agglutinin (PNA) and mostly Concanavalia ensiformis agglutinin
      (Con-A) and Ulex europaeus agglutinin (UEA-1) binding evolved in an opposite
      pattern with an increase of the labeling parallel to that of GB24 antibody
      binding. Electron microscopy showed that the fluorescence patterns observed
      correlated with increased access to the inner membrane of the acrosome. This was
      significant 60 min after the induction of acrosome reaction. Lectin binding could
      be a useful tool to examine the ability of sperm samples to undergo the acrosome
      reaction.

PMID- 8743351
TI  - Prognosis for fertility analyzing different variables in men and women.
AB  - A cohort of 123 infertile couples was studied by life tables over a 30-month
      follow-up period to determine the influence on reproductive prognosis of clinical
      features, namely the women's age, previous gestational events, evolution time,
      and a number of conditioning infertility factors. The cumulative pregnancy rate
      (CPR) was 60% at 30 months. Women aged 32 years or less had a CPR of 65% and
      those over 32 years had a CPR of 31%. Couples with previous pregnancy had a CPR
      of 88%, while those with primary infertility had a CPR of 45% (marginal
      statistical difference). The group with infertility evolution of 36 months or
      less had a CPR of 75% and those with greater than 36 months infertility evolution
      had a CPR of 43% (p < .05). With one conditioning infertility factor a CPR of 75%
      was found, and with multiple factors a CPR of 47% (p < .05) was found. With these
      results a grading chart was created using all the analyzed criteria, determining
      the proportion of pregnancies per number of negative points obtained; at greater
      grades the proportion of pregnancy was reduced (p < .01). This report establishes
      the prognostic value of different variables observed in the evaluation of
      infertile men and women, and a simple procedure to calculate the probability to
      achieve pregnancy is proposed.

PMID- 8743352
TI  - Alteration of collagen biosynthesis and analysis of type I and type III collagens
      of prostate in young rats following sex hormone treatments.
AB  - Two series of experiments were conducted to clarify the collagen biosynthesis and
      isolation of type I and type III collagens of young rats that received various
      sex hormone treatments. Evidence has been presented that (1) estradiol-17 beta
      treatment induces prostatic atrophy and suppresses the incorporation of
      [3H]proline into collagen in prostate; (2) administration of estradiol-17 beta
      increases the collagen content in the prostate; (3) localization of type I and
      III collagens in the interstitium of the prostate is detected by indirect
      immunofluorescence staining; (4) the ratio of type III collagen to type I
      collagen in the gland decreases following estradiol-17 beta treatment; and (5)
      neither treatment with testosterone nor administration of testosterone plus
      estradiol-17 beta in precastrated rats shows discernible effects on these
      valuables. These findings suggest that estradiol-17 beta increases the
      accumulation of collagen into the prostate with different extents of influence on
      the synthesis of type I and III collagens.

PMID- 8743353
TI  - Microsurgical epididymal sperm aspiration versus epididymal micropuncture with
      perivascular nerve stimulation for intracytoplasmic sperm injection to treat
      unreconstructable obstructive azoospermia.
AB  - A novel sperm collection method by epididymal micropuncture combined with
      perivascular nerve stimulation has been developed to obtain as many clean sperm
      as possible for IVF for patients with surgically irreparable vasal obstruction.
      To assess whether the new technique could improve the fertilization and pregnancy
      rates obtained when attempting microsurgical epididymal sperm aspiration (MESA)
      to retrieve epididymal sperm from such patients, a prospective randomized
      comparative study was conducted. Twenty-nine cycles of conventional MESA with
      ICSI were performed on 25 couples with congenital bilateral absence of the vas
      deferens (CBAVD) and four failed vasovasostomy cases (group 1). Thirty cycles of
      epididymal micropuncture with nerve stimulation with ICSI were performed on 28
      couples with CBAVD and two failed epididymovasostomy cases (group 2). The mean
      volume of epididymal fluid and sperm motility in group 2 was significantly higher
      than that in group 1 (p < .001). Both fertilization and pregnancy rates in group
      2 were significantly higher than those in group 1 (p < .001 and p < .03). This
      novel epididymal sperm collection method for ICSI can provide significantly
      higher fertilization and pregnancy rates than conventional MESA for ICSI.

PMID- 8743354
TI  - Hormonal evaluation in idiopathic oligozoospermia: correlation with response to
      clomiphene citrate therapy and sperm motility.
AB  - The reported response of sperm count to clomiphene citrate therapy in subfertile
      males with idiopathic oligozoospermia has been widely variable. The author
      postulates that this may be due in part to patient heterogeneity that may be
      reflected in pretreatment hormonal status. Seventeen patients with idiopathic
      oligozoospermia (mean +/- SE sperm density of 7.3 +/- 1.2 x 10(6) sperm/mL, mean
      FSH of 5 +/- 0.5 IU/L) were studied. Pretreatment basal LH, FSH, testosterone,
      free T4, and prolactin levels as well as LHRH-stimulated LH and FSH levels were
      examined in relation to pretreatment semen parameters and percent change in sperm
      count after a mean of 7.2 +/- 0.6 months of clomiphene citrate therapy. The
      percentage of motile sperm correlated with basal LH (r = .59, p = .02, n = 16)
      and free T4 levels (r = .62, p = .02, n = 13). Clomiphene citrate therapy was
      associated with a significant increase in total sperm count (mean percent change
      261 +/- 117, p = .02) and in total motile sperm count (mean percent change 370 +/
      216, p = .03). Percent change in total sperm counts and in total motile sperm
      counts correlated positively with pretreatment prolactin levels (r = .64, p =
      .007, n = 16, and r = .62, p = .01, n = 15), but not with the levels of other
      hormones. The results suggest that in patients with idiopathic oligozoospermia
      (1) clomiphene citrate therapy may be more effective in the subgroup of patients
      who have relatively higher prolactin levels, (2) basal and stimulated
      gonadotropin levels may not be helpful in predicting the response to clomiphene
      citrate therapy, and (3) lower sperm motility is associated with relatively
      higher free T4 and lower LH levels. The underlying mechanisms and the clinical
      utility of the current observations deserve further study.

PMID- 8743355
TI  - Environmental temperature and cryptorchidism: effects on pregnenolone-sulfatase
      of mice testicular tissue.
AB  - This study examined the capacity of abdominal organs, such as the scrotal testis,
      exposed to environmental temperature to hydrolyze pregnenolone sulfate. The
      cryptorchid state of exposure to 34 degrees C during 14 days decreased testis
      weight by 38 and 23%. But the enzymatic activity (nanomoles of free
      steroid/testis) was significantly higher (p < .05) compared with the control.
      Moreover, a rise in the environmental temperature combined with cryptorchidism in
      mice, two conditions that induced testicular damage, has been related to the
      elaboration of factors capable of modifying, through paracrine mechanism, the
      androgen biosynthesis. The presence of this factor could lead to an increase in
      the hydrolysis of pregnenolone sulfate, but as for cryptorchidism or high
      environmental temperature exposure, when cryptorchid mice were exposed to
      temperatures of 34 degrees C an apparent synergism of both conditions produced a
      decrease of 66% in testis weight. It would appear that the steroid sulfatase is
      predominantly located in the interstitial epithelium. This study suggests that
      cryptorchidism and hyperthermia damage the tubular epithelium by different
      mechanisms.

PMID- 8743356
TI  - Treatment of tuberculous epididymitis by intratunical rifampicin injection.
AB  - The results of treating 4 patients with tuberculous epididymitis by rifampicin
      injection into the tunica vaginalis sac were compared with the results in another
      4 patients treated with the common oral antituberculous drugs. Oral treatment
      consisted of daily administration of rifampicin (600 mg), isoniazid (300 mg), and
      ethambutol (25 mg/kg body weight). Rifampicin (600 mg) was injected
      intratunically every 4 to 6 days. Treatment continued for 6 months in both
      groups, with 3 months follow-up thereafter. Periodic clinical assessment as well
      as semen and hydrocele fluid examination were performed. In the intratunical
      injection group, epididymal swellings disappeared in 3 to 6 months; semen and
      hydrocele fluid became sterile in 4 months. The oral group showed partial
      diminution of the epididymal mass in one patient only; one patient developed
      scrotal fistula. Semen remained positive for tubercle bacilli, and hydrocele
      fluid became negative in one patient only. The satisfactory results with the
      intratunical rifampicin administration seem to be due to the drug reaching the
      epididymis in high concentrations. The tunica vaginalis is a part of the
      peritoneum and, like it, is believed to have a high absorptive power.
      Furthermore, the intratunical injection treatment uses a single drug, in contrast
      to the oral therapy, which, by its multidrug administration, enhances the
      incidence of side effects.

PMID- 8743357
TI  - Experimental telemanipulation in endoscopic surgery.
AB  - Today's rigid endoscopic instruments limit the intracorporeal mobility of the
      surgical tool and are a severe impediment for the further spread of endoscopic
      techniques in operative medicine. Since 1992 flexible, steerable instruments with
      additional links for pivoting and rotating the tip have been developed and
      experimentally evaluated. The latest versions of this series of instruments are
      equipped with electromotors for better handling. The next aim in this development
      is a fully mobile telemanipulator with six motion axes dedicated to use in
      endoscopic surgery. Its first tests are planned for 1995. For successful
      operation of an electric telemanipulator, the man-machine interface (MMI) is of
      cardinal importance. For the definition of surgical requirements for the MMI, a
      conventional master-slave manipulator designed for technical application was
      modified for use in guiding a laparoscopic instrument. Master and slave sites of
      the system were 1.3 km apart and linked by means of a fiber-optic cable. Using
      this modified telepresence system, remote laparoscopic cholecystectomy was
      feasible in a phantom model. In a standardized test series using a test parcours,
      different parameters of the control system were modified, and their influence on
      the execution time of the parcours tasks was recorded. Well-suited parameter
      configurations were found and allowed experimental verification and completion of
      the important aspects of our concepts for development of an endoscopic
      manipulator MMI.

PMID- 8743358
TI  - Laparoscopic epiplopexy of the greater omentum and epiploic appendices in the
      salvaging of dysfunctional peritoneal dialysis catheters.
AB  - The success of peritoneal dialysis in the management of chronic renal failure
      depends on the proper function of the implanted catheter. Common causes of
      catheter drainage dysfunction include an omental wrap or blockage of the catheter
      by other intraperitoneal structures. The present report describes laparoscopic
      management of five patients with outflow obstruction of a peritoneal dialysis
      catheter. Epiplopexy of the greater omentum or epiploic appendices was employed
      in all cases to prevent potential recurrence of catheter dysfunction. Technique
      and other procedural details are described. Long-term successful function of the
      peritoneal dialysis catheter was restored in all patients.

PMID- 8743359
TI  - Thoracoscopic treatment for spontaneous pneumothorax in patients over 50 years
      old: a comparison with younger patients.
AB  - The purpose of this study was to compare thoracoscopic treatment for spontaneous
      pneumothorax in patients over 50 years old (OG) and younger patients (YG).
      Thoracoscopic treatment was performed in both groups using the same patient
      selection criteria: persistence of an air leak after tube thoracostomy drainage,
      ipsilateral recurrence, and bilateral pneumothoraces. Thoracoscopic treatment was
      performed in nine older patients (OG) over a two-year period. Their ages ranged
      from 50 to 81 years (average: 66 years). The mean operative time, postoperative
      drainage period, and hospital stay after surgery were 120 min, 6.3 days, and 10.7
      days, respectively. In the YG, these indices were 71 min, 1.5 days, and 5.3 days,
      respectively. Each factor was significantly prolonged in the OG (p < 0.05).
      However, there were no major perioperative complications or recurrences 3-24
      months after surgery in either group. Thus, thoracoscopic surgery is also
      effective in the treatment of spontaneous pneumothorax in patients over 50 years
      old.

PMID- 8743360
TI  - Experimental laparoscopic aortic aneurysm resection and aortobifemoral bypass.
AB  - The purpose of the present study was to develop a technique for laparoscopic
      aortic aneurysm resection and aortobifemoral bypass through an anterior
      retroperitoneal approach. Eight piglets weighing between 75 and 80 kg were
      anesthetized. The concepts of Shumacker's anterior retroperitoneal exposure of
      the aorta were modified to allow laparoscopic exposure of the aorta in the first
      four animals. The other four animals were treated as if they had an aortic
      aneurysm. The piglet is placed in a supine position. The first port (1.5 cm) is
      placed laterally near the tip of the 12th rib. As much dissection of the
      retroperitoneum as possible is performed digitally through this port. A second
      port (1.5 cm), through which an abdominal lift device and a peritoneal retractor
      will be inserted, is created superiorly just lateral to the left rectus sheath,
      and a plane is developed that joins the original dissected space. Two other ports
      (1.5 cm) are placed in the flanks in a plane inferosuperior to the first port.
      The surgeon will use two of the lateral ports, and the third one is for the
      laparoscope. The last two ports (1.5 cm), from which the assistant will work, are
      placed in the left paramedian region. Using this approach, we performed four
      aortobifemoral bypasses in an average of 4.5 h after conventional i.v.
      heparinization (100 IU/kg) with minimal bleeding (blood loss < 550 cc). After
      infrarenal aortic cross-clamping, the external iliac and caudal vessels were
      either tied with 0-chromic or occluded with laparoscopic bull-dogs. The aorta was
      opened, and bleeding lumbar arteries and the aortoiliac junction were sutured
      with 4-0 Prolene. The vascular graft was sutured end-to-end to the aortic stump
      with running 4-0 Prolene. Tunneling to the femoral regions was made easy by the
      position of the animal. No mortality occurred before sacrifice of the animals.
      This laparoscopic animal model paves the way for human aortic aneurysm
      replacement.

PMID- 8743361
TI  - The influence of three-dimensional video systems on laparoscopic task
      performance.
AB  - Many laparoscopic surgeons feel constrained by the two-dimensional (2-D) view
      provided by video monitors. Video-eye-hand coordination is further complicated by
      the diminished tactile feedback blunted by elongated instruments. Video systems
      capable of receiving and displaying three-dimensional (3-D) images are now
      available for laparoscopy. First-generation 3-D systems have been marketed with
      the promise of significant time savings in laparoscopic procedures compared with
      2-D optics. We assessed whether laparoscopic task performance was better in 2-D
      or 3-D among individuals with varying levels of laparoscopic experience. Five
      different tasks were performed in random order using both 2-D and 3-D technology
      by medical students (n = 10), inexperienced surgical residents (n = 10), and
      laparoscopic attending surgeons (n = 10). There was no significant difference in
      task performance between 2-D and 3-D among groups performing simple or difficult
      tasks, although suturing and knot-tying were performed 12% (p = 0.06) faster in 3
      D by all groups. With repetition of tasks three times, the difference between the
      2-D and 3-D systems was indistinguishable. Subjective assessment of the video
      systems by participants revealed that only 46% (p = 0.72) preferred working in
      three dimensions, despite 60% (p = 0.27) sensing more motor control in 3-D. Our
      results suggest that first-generation 3-D video systems offer no significant
      advantage to the novice or expert surgeon performing laparoscopic procedures.
      Further trials with the next generation of 3-D video systems and a larger sample
      size may support the trend favoring 3-D for more complex maneuvers, such as
      suturing and knot-typing.

PMID- 8743362
TI  - Intraoperative biliary tree imaging with cholyl-lysyl-fluorescein: an
      experimental study in the rabbit.
AB  - Iatrogenic bile duct injury during cholecystectomy is the most serious
      complication of this surgical procedure. Initial reports suggest that this
      complication is particularly troublesome during laparoscopic cholecystectomy.
      Proper identification of the biliary anatomy in the subhepatic region is the only
      way to avoid this catastrophe. The potential benefits of a simple, reliable
      method for intraoperative delineation of biliary anatomy are self-evident. In
      this experimental study on rabbits, we show how the simple i.v. injection of a
      fluorescent bile salt, cholyl-lysyl-fluorescein, enables the surgeon to visualize
      the entire biliary tree in anatomic detail.

PMID- 8743363
TI  - Hemodynamic and respiratory changes during laparoscopic cholecystectomy with high
      and reduced intraabdominal pressure.
AB  - Laparoscopic cholecystectomy (lapchole) is a safe procedure. Most of the
      complications are operation related. The complications related to increased
      intraabdominal pressure (IAP) are well recognized, but not emphasized enough. The
      changes in physiological parameters at different IAPs were studied to evaluate
      the usefulness of reduced IAP in minimizing these changes. Thirty consecutive
      patients consisting of 16 ASA III, 2 ASA IV, and the rest ASA I and II, underwent
      lapchole under high and reduced IAP. The mean arterial pressure (MAP), heart rate
      (HR), arterial oxygen saturation (SaO2), airway pressure (AWP), and end-tidal
      carbon dioxide (ETCO2) were recorded before insufflating carbon dioxide (T1),
      with IAP of 14 mm Hg (T2) and IAP of 6 mm Hg or less (T3). At T2, MAP increased
      by 41.15%, AWP by 44.3%, and ETCO2 by 20.5% as compared to T1 (p < 0.001). HR and
      SaO2 showed no significant changes. At T3 there was an increase in MAP by 24.94%,
      in AWP by 10%, and ETCO2 by 10.6% with no significant changes in HR and SaO2.
      Thus, operating under reduced IAP may be beneficial to the patients with
      decreased cardiopulmonary reserve, especially while undergoing long surgical
      procedures.

PMID- 8743364
TI  - Laparoscopic appendectomy: comparison with open appendectomy in 720 patients.
AB  - We conducted a review of laparoscopic appendectomies (LA) and open appendectomies
      (OA) over a 3-year period, including 720 patients (253 LA, 467 OA) who underwent
      appendectomy during the study period. Computer records were reviewed with respect
      to demographics, length of stay, operating room time, operating room cost,
      hospital cost, and morbidity. All patients were sent surveys to assess their
      posthospitalization recovery. The LA patients had significant shorter hospital
      stays (2.06 days vs. 3.44 days, p < .001), lower morbidity rates (5 vs 14%, p <
      .02), and comparable overall hospital costs ($4,800 vs. $4,950). The LA patients
      also reported less postoperative pain and were able to return to work sooner. Our
      results show that LA can significantly decrease morbidity and hospital stay with
      a comparable hospital cost and result in quicker patient recovery.

PMID- 8743365
TI  - Cerebral oxygen metabolism measured by near-infrared laser spectroscopy during
      laparoscopic cholecystectomy with CO2 insufflation.
AB  - To clarify the influence of carbon dioxide (CO2) on cerebral oxygen metabolism
      and blood volume during laparoscopy with CO2 insufflation in 12 patients who
      underwent laparoscopic cholecystectomy, changes in the concentrations of cerebral
      oxyhemoglobin (HbO2), reduced hemoglobin (HbR), total hemoglobin (total Hb), and
      oxidized cytochrome aa3 (Cyt aa3) were measured using near-infrared laser
      spectroscopy. Anesthesia was maintained with nitrous oxide (66%)-oxygen
      sevoflurane. Pneumoperitoneum was maintained at an endoabdominal pressure of 10
      to 12 mm Hg using CO2. Minute ventilation was constant before and after CO2
      insufflation. End-tidal CO2 tension (PETCO2) increased significantly, from 33.9
      +/- 1.3 to 52.8 +/- 3.3 mm Hg, after CO2 insufflation. The concentration of HbO2
      increased significantly, from 0 to 7.3 +/- 2.8 mumol/L, after CO2 insufflation.
      The concentration of HbR increased significantly, from 0 to 2.2 +/- 1.2 mumol/L,
      after CO2 insufflation. Therefore, the concentration of total Hb increased
      significantly, from 0 to 8.8 +/- 3.3 mumol/L after CO2 insufflation. The
      concentration of Cyt aa3, however, did not change significantly during
      pneumoperitoneum. These results suggest that cellular respiration remained intact
      despite a concomitant increase in PETCO2 and cerebral blood volume during
      laparoscopy with CO2 insufflation.

PMID- 8743366
TI  - Laparoscopic anterior resection: a consecutive series of 84 patients.
AB  - Laparoscopic colorectal surgery is in its infancy. From a series of over 200
      colorectal procedures undertaken over the last 30 months, we have performed 84
      anterior resections. In 55 women and 29 men, median age 64 years (range 32-86),
      median weight 72 kg (range 36-125), surgery was undertaken for benign pathology
      (n = 57) and adenocarcinoma (n = 27). Anterior resection was completed
      laparoscopically in 75 cases (89%) with a median operating time of 210 min (range
      85-420). Minor morbidity occurred in 17 patients (20%) with major morbidity in 10
      cases (12%). There was one post-operative death. Flatus was passed a median of
      two days (range 1-7) after surgery and feces at a median of four days (range 2
      9). Total hospital stay was six days (range 2-33). Delayed morbidity during a
      maximum of 30 months' follow-up included two anastomotic strictures but no
      evidence of malignant seeding. Laparoscopic anterior resection appears both
      feasible and safe for both benign and malignant disease, with the caveat that
      long-term outcome in malignant disease is not yet available.

PMID- 8743367
TI  - Safety of laparoscopic cholecystectomy on a teaching service: a prospective
      trial.
AB  - In a prospective audit of our first 213 laparoscopic cholecystectomies (LC), we
      compared the results obtained by qualified surgeons to those obtained by
      residents. The first group started performing LC after undergoing formal
      laboratory laparoscopic courses. The second group was introduced to LC by
      standard attending-resident teaching in the operating room. In all, 137 LC wer
      performed by qualified surgeons and 76 by residents. Patients' clinical and
      laboratory characteristics were not significantly different in the two groups.
      The conversion rate to laparotomy (11.5% and 12.5%), mean duration of surgery (88
      and 83 min), iatrogenic perforation of the gallbladder (16% and 18.5%), "lost
      stones" (7% and 4%), use of drains (12% and 13%), and extension of the umbilical
      port incision (about 30% in both groups) were similar in the two groups. The
      incidence of biliary (3% and 4%) and infectious (3.5% and 4%) complications was
      equivalent in both groups. We conclude that with the traditional attending
      resident approach to surgical education, residents safely and quickly acquire the
      necessary skills to perform LC without jeopardizing the safety of patients.

PMID- 8743368
TI  - Vena cava injuries during laparoscopic cholecystectomy.
AB  - Two instances of vena cava injury occurring during insertion of a new trocar for
      laparoscopic surgery are presented. The mechanism of injury in each case was
      identical. These injuries are extremely rare, and fortunately both patients
      survived. Any new instrument that is purported to be an improvement over existing
      ones should be critically evaluated so that needless and unnecessary injuries
      such as these can be avoided.

PMID- 8743369
TI  - Postoperative gangrenous peritonitis after laparoscopic cholecystectomy: a new
      complication for a new technique.
AB  - We report a case of anaerobic peritonitis with bowel emphysema, but no hollow
      organ perforations, following gallbladder removal for acute acalculous
      cholecystitis using a laparoscopic procedure in a diabetic patient. Management
      consisted of profuse peritoneal irrigation and zipper laparostomy. After a long
      postoperative period, the patient recovered without sequelae. The patient
      suffered typical acute cholecystitis with empyema and a diabetic status;
      anaerobial flora is frequent in these cases. The patient was operated on by means
      of a closed technique without contact with either air or oxygen. Moreover, CO2
      injection into the peritoneal cavity with this technique, along with gallbladder
      rupture, created an ideal medium for anaerobial growth. We suggest that
      acalculous cholecystitis in diabetic patients could represent a contraindication
      for laparoscopic cholecystectomy; alternatively, open cholecystectomy should at
      least be considered when gallbladder rupture occurs during laparoscopy.

PMID- 8743370
TI  - Placement of drains during laparoscopic surgery.

PMID- 8743371
TI  - Thoracoscopic splanchnicectomy: technique and case report.
AB  - Division of the greater and lesser splanchnic nerves using a thoracoscopic
      approach is presented. Splanchnicectomy has been described by several surgeons as
      a means of palliating chronic pancreatic pain caused by either alcohol-related
      chronic pancreatitis or pancreatic cancer. Thoracoscopy represents a minimally
      invasive approach to the splanchnic nerves. Current three-chip cameras enable a
      sixfold to eightfold magnification of intrathoracic structures, and the nerves
      are easily identified. The role of this operation in the thoracic surgeon's
      armamentarium awaits larger series of patients with longer follow-up.

PMID- 8743372
TI  - Laparoscopy in the management of Meckel's diverticulum.
AB  - As the use of and familiarity with minimally invasive surgery continue to
      increase in general surgery, the laparoscopic management of symptomatic and
      asymptomatic Meckel's diverticulum will become more commonplace. A case of
      symptomatic Meckel's diverticulum is presented here to discuss operative
      decisions and laparoscopic options, specifically the use of frozen section to
      assure complete resection of any ectopic tissue present.

PMID- 8743373
TI  - Video-laparoscopic reduction of an intrathoracic stomach.
AB  - A paraesophageal hiatal hernia is caused by a defect in the anterolateral aspect
      of the diaphragmatic esophageal hiatus. Most commonly, the stomach migrates into
      the hernia sac. Although most patients are asymptomatic, repair is advised at the
      time of the diagnosis because of the high morbidity and mortality associated with
      surgery for the complications of paraesophageal hiatal hernias. However, because
      of the morbidity associated with conventional surgical techniques, there has been
      great reluctance to subject an asymptomatic patient to surgical repair. We report
      a minimally invasive technique for the reduction of a paraesophageal hiatal
      hernia and repair of the diaphragmatic hiatal defect. Video laparoscopy, with its
      attendant low morbidity, may be the ideal technique for the repair of
      paraesophageal hiatal hernias.

PMID- 8743374
TI  - Simultaneous laparoscopic cholecystectomy and laparoscopically assisted vaginal
      hysteroadnexectomy.
AB  - As a consequence of the wide applications of operative laparoscopy and
      thoracoscopy, simultaneous surgical procedures have been carried out
      endoscopically. We report a 51-year-old woman treated by simultaneous
      laparoscopic cholecystectomy and celioscopically assisted vaginal
      hysteroadnexectomy for hydropic calculous gallbladder, uterine myomas, and
      bilateral ovarian policystosis. These procedures were carried out using six
      abdominal trocar sites, and the gallbladder was removed through the colpotomic
      access. The patient had an uncomplicated postoperative course and was discharged
      on postoperative day 5. In our opinion, the multidisciplinary laparoscopic
      approach, with the original technical solutions, represents an effective,
      minimally invasive method of treatment that gives new perspective about the
      indications and the treatment of similar cases.

PMID- 8743375
TI  - Laparoscopic approach for treatment of a primary splenic cyst.
AB  - We present the case of a 24-year-old woman with a symptomatic primary splenic
      cyst, and we relate our first experience with laparoscopic resection of the
      extrasplenic wall of the cyst. The procedure was successful, and the patient was
      discharged asymptomatic two days following surgery. We describe the surgical
      technique used and comment on some pathologic and tactical aspects. We conclude
      by remarking on the association of the beneficial advantages of minimally
      invasive surgery with the demand for more conservative splenic surgical
      procedures. Therefore, laparoscopic partial cystectomy may be a useful
      alternative for patients who require an effective treatment for nonparasitic
      splenic cysts.

PMID- 8743376
TI  - Introduction of two new laparoscopic nooses.
AB  - Two devices for the temporary occlusion of tubular structures are introduced.
      They are constructed by combining a double-looped suture with a catheter segment.
      By this means, a terminal noose is created that can temporarily and
      atraumatically engage a vessel or other tubular structure. These devices can be
      used to obtain proximal and distal control of short segments without the need for
      bulky laparoscopic instruments in the operative field. The devices do not require
      purchase of any major equipment and can be made with any large-gauge polyfilament
      suture material and catheters available in the operating room.

PMID- 8743402
TI  - Glucuronidation of diflunisal, (-)-morphine, 4-nitrophenol, and propofol in liver
      microsomes of two patients with Crigler-Najjar syndrome type I.
AB  - In vitro glucuronidation was studied in liver microsomes from two patients with
      Crigler-Najjar type I (CN-I) disease and compared with the activity measured in
      microsomes prepared from six control human livers. The UDP
      glucuronosyltransferase (UGT) activity was determined toward the following
      substrates: 4-nitrophenol, propofol, (-)-morphine (formation of the 3
      glucuronide), and diflunisal (formation of the phenolic and acyl glucuronides).
      Glucuronidation of 4-nitrophenol was reduced in one of the CN-I livers (CN-I No.
      1) (0.9 nmol min(-1)mg(-1)) and normal in the other CN-I liver (CN-I No. 2) (3.5
      nmol min(-1) mg(-l)) compared to the control livers (5.6 +/- 29 nmol min(-1) mg(
      1)), mean +/- S.D.). Propofol glucuronidation was not detectable (i.e. less than
      0.100 nmol min(-l) mg(-1) in the CN-I No. 1 liver and normal in the CN-I No. 2
      liver (1.78 nmol min(-1) mg(-1) against 1.52 +/ 0.72 nmol min(-l) mg(-) in the
      control livers). The glucuronidation of (-)-morphine to the 3-glucuronide and the
      formation of the phenolic and acyl glucuronides of diflunisal were normal in both
      CN-I livers compared to the control livers. Our results show that CN-I patients
      are heterogeneous regarding UGT activity toward the phenolic substances 4
      nitrophenol and propofol.

PMID- 8743403
TI  - A pharmacokinetic comparison of cefadroxil and cephalexin after administration of
      250, 500 and 1000 mg solution doses.
AB  - The pharmacokinetics of cefadroxil and cephalexin were examined following single
      oral doses of either 250, 500 or 1000 mg to a total of 36 healthy volunteers. The
      volunteers were divided into groups of 12 per dose-group and solution doses of
      cefadroxil or cephalexin were administered after an overnight fast according to a
      crossover design for the cephalosporins but not for doses. Serial blood and urine
      samples were collected from each individual and were analyzed for cefadroxil or
      cephalexin using validated HPLC assays with UV detection. The individual subject
      plasma concentration-time data for each cephalosporin were analyzed using
      noncompartmental methods. Profiles for cephalexin in plasma showed sharper and
      higher peaks than those for cefadroxil. Although values for the peak
      concentrations (Cmax) for cefadroxil were lower than that of cephalexin, the
      levels of cefadroxil in plasma and urine remained above the reported minimum
      inhibitory concentrations of susceptible organisms for longer period of time than
      those of cefalexin. The elimination half-life (t1/2) of cefadroxil (about 2 h)
      was significantly longer than that of cephalexin (about 1 h). The values for Cmax
      and AUC0-infinity values for both these cephalosporins showed dose-proportional
      increase, whereas t1/2, renal clearance (CLR) remained independent of dose. These
      observations confirm that cefadroxil and cephalexin obey linear pharmacokinetics.
      The CLr of both the cephalosporins were significantly higher than the average
      glomerular filtration rate at each dose level. The urinary recovery (% Xu) of
      each cephalosporin, accounted for over 80 per cent of the administered dose, and
      no significant differences in % Xu were observed between the two cephalosporins.
      These data suggest that the systemic availability of cefadroxil and cephalexin is
      similar at each dose level.

PMID- 8743404
TI  - Lipid emulsions of palmitoylrhizoxin: effects of composition on lipolysis and
      biodistribution.
AB  - Four types of lipid emulsion for highly lipophilic antitumour agent RS-1541 (13-O
      palmitoylrhizoxin) with mean particle diameters of 200-260 nm were prepared using
      soybean oil (SOY) or dioctanoyldecanoylglycerol (ODO) for the oil phase and
      lecithin (LEC) or polyoxyethylene-(60)-hydrogenated castor oil (HCO-60) for
      surfactants. The lipolysis rate of HCO-60-emulsified emulsions by lipoprotein
      lipase was much slower than that of LEC-emulsified emulsions. Particle sizes of
      emulsions incubated in plasma with the lipase for six hours were 75%, 79%, 101%,
      and 93% of initial values for SOY/LEC, ODO/LEC, SOY/HCO-60, and ODO/HCO-60
      emulsions, respectively, showing an apparent size decrease for LEC-emulsified
      emulsions. In rats, uptake clearance values of SOY/LEC and ODO/LEC emulsions of
      RS-1541 in the reticuloendothelial system (RES) were 81.2 and 135.3 mL h(-1),
      respectively, and AUC values were 4.0 and 1.3 microg h mL(-1), respectively. In
      contrast, RES uptake clearances of HCO-60 emulsions of RS-1541 were considerably
      lower (4.2 mL h(-1) for SOY/HCO-60; 2.2 mL h(-1) for ODO/HCO-60), resulting in
      high AUC values (35.4 microg h mL(-1) for SOY/ HCO-60; 63.9 microg h mL(-1) for
      ODO/HCO-60). The concentrations of RS-1541 in tumour tissues after an intravenous
      administration of ODO/HCO-60 emulsions of RS-1541 to mice bearing solid tumour
      M5076 sarcoma were about ten times higher than those after the administration of
      SOY/LEC emulsions. These results indicate that HCO-60 emulsions, compared with
      conventional LEC emulsions, are more stable to lipoprotein lipase and show low
      uptakes by RES organs, long circulations in the plasma, and high distributions in
      tumours. Thus, these sterically stabilized emulsions could show potential as
      effective carriers for highly lipophilic antitumour agents to enhance the drug
      delivery in tumours.

PMID- 8743405
TI  - Lipid emulsions of palmitoylrhizoxin: effects of particle size on blood
      dispositions of emulsion lipid and incorporated compound in rats.
AB  - Emulsion formulations of various particle sizes for the highly lipophilic
      antitumour agent, RS-1541 (13-O-palmitoylrhizoxin), were prepared using
      dioctanoyldecanoylglycerol (ODO) as lipids and polyoxyethylene-(60)-hydrogenated
      castor oil (HCO-60) as a surfactant. These emulsions were evaluated as injectable
      drug carriers and compared with a colloidal solution. Both in vitro and in vivo
      after i.v. administration, RS-1541 was distributed into lipoproteins from the
      colloidal solution. When applied as emulsions of various particle sizes (124-419
      nm) in vitro, RS-1541 was retained and stabilized within the emulsions. In the in
      vivo study, however, retention of RS-1541 in the emulsions after i.v. injection
      depended on their size. The small-particle emulsions (94-112 nm) resulted in long
      retention, and the large-particle emulsions (415-474 nm) led to short retention.
      Lipolysis rates of emulsion particles by lipoprotein lipase also depended on
      their size, indicating rapid lipolysis for small-particle emulsions (133 nm).
      However, the lipolysis was not such an extensive one, showing 10-30% release of
      capric acid from ODO within 6 h. Blood dispositions of capric acids approximately
      paralleled those of RS-1541 after i.v. injection of various particle size
      emulsions (130-368 nm) to rats, although relatively rapid eliminations of capric
      acids compared with RS-1541 were observed for the small-particle size emulsions
      (130 nm). These results suggest that when injected as emulsion formulations, the
      highly lipophilic antitumour agent, RS-1541, has behaviour similar to that of the
      emulsion particles in the body, which is dependent on the size of the latter.
      Thus, by properly selecting the particle size, lipid emulsions consisting of ODO
      and HCO-60 are expected to be effective and useful DDS carriers for RS-1541.

PMID- 8743406
TI  - Dose dependent pharmacokinetics of naproxen in man.
AB  - The pharmacokinetics of one of the most widely used non-steroidal
      antiinflammatory drugs, naproxen, were studied in 28 healthy human volunteers at
      the two most commonly used dose levels, viz., 250 mg and 500 mg, in a cross-over
      design. The plasma levels of naproxen were analysed by a modified high-pressure
      liquid chromatography method. The plasma concentrations at higher doses were not
      proportional to dose, indicating a non-linearity in the pharmacokinetics at the
      dose levels studied; this finding is new since earlier studies had studied only
      higher doses and assumed that at lower doses the pharmacokinetics would be
      linear. There was, however, no significant difference in the elimination half
      life (rate constant), time to reach peak concentration (Cmax), mean residence
      time (MRT), or area under first moment curve (AUMC). The clearance and
      distribution volume of naproxen were substantially increased at higher dose
      resulting in statistically lower proportional concentration and the total area
      under the curve (AUC). These observations are explained on the basis of a change
      in the plasma protein binding resulting in more free naproxen available for
      quicker clearance and wider penetration into tissues. These findings have several
      important clinical implications for the long-term use of naproxen as an
      antiarthritic drug. It is proposed that the clinical efficacy of naproxen can be
      increased and side-effects reduced by giving it in small divided doses instead of
      large doses.

PMID- 8743407
TI  - Programmed cell death in the tobacco hornworm, Manduca sexta: alteration in
      protein synthesis.
AB  - The metamorphic death of the labial glands of the tobacco hornworm, Manduca
      sexta, occurs during a 4 day period during larva-to-pupa metamorphosis. The
      earliest changes marking the death of the cell, all occurring on the first day,
      are a sharp drop in protein synthesis, coupled with the selective survival or
      upregulation of a few messages. An early rearrangement of the rough endoplasmic
      reticulum is presumably related to the generalized decrease in protein synthesis.
      Lysosomal acid phosphatase also begins to increase very early, and ultimately the
      bulk of the cytoplasm is destroyed in autophagic vacuoles, but activation of
      lysosomes does not account for the decreased rate of synthesis. The mechanism by
      which most protein synthesis is depressed remains under investigation.

PMID- 8743408
TI  - Programmed cell death during metamorphosis in the blow-fly Calliphora vomitoria.
AB  - During metamorphosis, the salivary glands of the blow-fly undergo programmed cell
      death. Data is presented indicating that this programmed cell death does not in
      many respects emulate classical apoptosis. The cells are seen to vacuolate and
      swell rather than condense and shrink. There appears to be a transient
      enhancement in autophagy and an increase in acid phosphatase activity. This is
      followed by the characteristic appearance of ribosomal and extracisternal sources
      of the enzyme leading to autolysis. There appears to be no lysosomal leakage of
      acid phosphatase. As in apoptosis, the mitochondria persist until the cell
      fragments. The nucleus, however, does not show the distinct chromatin margination
      and blebbing that is typical of apoptosis. These changes are compared with
      necrotic changes induced by experimental anoxia. Overall the results show that a
      programmed cell death distinct from classical apoptosis is taking place.

PMID- 8743409
TI  - Evidence for transcriptional modulation but not acid phosphatase expression
      during programmed cell death in the colonial tunicate Botryllus schlosseri.
AB  - Botryllus schlosseri is a clonally modular ascidian in which asexually derived
      adults (zooids) exhibit developmental synchrony. At the conclusion of the
      blastogenic (asexual) cycle every 5 days at 21 degrees C, all zooids within a
      colony die simultaneously in 24 hours and are replaced by a new asexual
      generation of zooids. This cyclical process, called takeover, involves the
      selective destruction of the zooid's visceral tissues which include the pharynx,
      esophagus, stomach, intestine, endostyle, neural complex and heart, whereas bud
      tissues and mesenchymal components (muscle and blood cells) remain unaffected.
      Ultrastructural analysis indicates that the most prevalent form of cell death
      occurs by apoptosis, although necrotic changes are also observed in several
      tissues (i.e., stomach and intestine). Blood-derived macrophages and neighboring
      cells subsequently engulf visceral tissues, reducing the zooid to the size of a
      small vesicle. Here, we have tested the possibility that acid phosphatase, a
      hydrolase whose presence is associated with cell death in several invertebrate
      systems, could account for some of the regressive changes observed during
      takeover. Our observations indicate that acid phosphatase (AP) activity was
      selectively localized in the gut of parent zooids during the growth phase of the
      cycle, with the stomach exhibiting the most intense histochemical staining on
      tissue sections. As zooid regression progressed during takeover, stomach AP
      staining gradually disappeared. Other visceral tissues never became AP-positive.
      Therefore, this hydrolase appears to play a minimal role in zooid death. In order
      to characterize genes whose expression pattern was selectively altered during
      takeover, we have carried out differential mRNA display analysis. We report on
      two genes, 790.3 and 790.4, that are down- and upregulated, respectively, during
      this process. Collectively, these findings indicate that the takeover phase of
      blastogenesis in Botryllus involves modulated gene expression.

PMID- 8743410
TI  - Apoptosis of larval cells during amphibian metamorphosis.
AB  - Programmed cell death occurs in a variety of organs during amphibian
      metamorphosis and is usually identified by electron microscopy as apoptosis or
      its modifications. Because of the massive cell death that occurs during a short
      period, amphibian organs serve as an ideal model system for the study of
      mechanisms underlying programmed cell death. In this article, a series of
      morphological changes in apoptosis from their nuclear changes to removal by
      phagocytic macrophages is reviewed, mainly in the small intestine of
      metamorphosing Xenopus laevis tadpoles. It is well known that cell death during
      amphibian metamorphosis is under the control of thyroid hormone (TH), and changes
      in gene expression induced by TH have been recently analyzed in a few Xenopus
      organs. On the other hand, there is a growing body of evidence that cell death is
      regulated by various kinds of local factors. For example, roles of interactions
      with other tissue cells and/or participation of immunocompetent cells in cell
      death have been experimentally shown. Therefore, to clarify the mechanisms of
      this complicated process, it is important at present that TH-induced changes in
      gene expression of each cell type comprising the organ are chronologically
      examined by combining morphological and molecular biological techniques.

PMID- 8743411
TI  - Morphology and significance of programmed cell death in the developing limb bud
      of the vertebrate embryo.
AB  - Cell death constitutes a basic mechanism accounting for many morphogenetic and
      histogenetic events during normal and abnormal development of embryonic organs
      and tissues. This article focuses on the major areas of mesodermal cell death
      occurring during vertebrate limb development. In early stages of limb
      development, cell death appears to reduce the amount of mesodermal tissue
      destined to form the anlage of the autopodium. In later stages, cell death plays
      a role sculpturing the shape of the digits. The morphology of the dying cells
      corresponds with apoptosis, but internucleosomal DNA fragmentation by
      endonuclease activation does not appear to be a precocious feature. The cell
      death program can be inhibited in vivo and in vitro by changing the environmental
      conditions of the prospective dying cells up to 6-10 h before death. In this
      review, we survey possible factors controlling the establishment of the cell
      death program. Information concerning the biochemical basis of cell death in the
      developing limb is also revised. Finally, the possible role of genes whose
      pattern of expression is coincident with the dying processes is discussed.

PMID- 8743412
TI  - Hepatocyte death following transforming growth factor-beta 1 addition.
AB  - Apoptosis is a morphological term which describes a sequence of events finally
      leading to cell death. In epithelial organs, induction of cell death is closely
      linked to an inhibitor of epithelial growth, transforming growth factor-beta 1
      (TGF-beta 1). In this paper, we describe the morphology of TGF-beta 1-induced
      apoptosis in hepatocytes of the hyperplastic liver and primary cultures.
      Chromatin condensation, a hallmark of apoptosis, was observed in primary
      hepatocytes by confocal and vital UV microscopy. In addition, we have applied the
      morphological detection of DNA strand breaks both by in situ tailing (ISTAIL) and
      in situ nick translation (ISNT).

PMID- 8743413
TI  - Activation of physiological cell death mechanisms by a necrosis-causing agent.
AB  - Cell death is an important physiological process, but it can be triggered by both
      physiological and nonphysiological stimuli. The product of the bcl-2 gene has the
      ability to inhibit a physiological cell death process that can be activated by a
      variety of physiological signals, such as growth factor deprivation. This report
      describes the use of electron microscopy to examine the effects of two cytotoxic
      drugs on factor-dependent cells that constitutively express the human bcl-2 gene.
      Although all cells treated with sodium azide showed changes typical of necrosis,
      in the absence of Bcl-2 the cells died more rapidly and also displayed features
      of apoptosis. The fact that Bcl-2 could delay cell death argues that cells can
      activate internal cell death mechanisms to commit suicide before they are killed
      by a cytotoxin. Northern analysis showed that growth factor did not preserve
      viability of the cells through induction of bcl-2. However, growth factor may
      prevent activation of the physiological cell death mechanisms that bcl-2 can
      control. This process may constitute a primitive defense response, and blocking
      it may provide a means of limiting damage caused by otherwise sublethal injuries.

PMID- 8743414
TI  - Apoptotic morphology reflects mitotic-like aspects of physiological cell death
      and is independent of genome digestion.
AB  - Several hallmarks characterize what has come to be recognized as a common
      physiological process of cell death. In particular, the two defining
      characteristics are the apoptotic morphology of cell shrinkage and chromatin
      condensation originally described by Kerr et al. [(1972) Br. J. Cancer, 26:239
      256] and the prelytic digestion of genomic DNA of the dying cell, as noted first
      by Wyllie [(1980) Nature, 284:555-556] and Russell et al. [(1982) J. Immunol.,
      128:2087-2094]. Many suicidal stimuli are able to modulate this process; each of
      these suicidal inducers activates cell death via a specific pathway. While it
      remains to be established, we hypothesize that a single mechanism of
      physiological cell death pertains in all cases [Ucker (1991) New Biol., 3:103
      109; Ucker et al. (1994) Immunol. Rev., 142:273-299]. The various modulatory
      processes act afferently on this single effector pathway. We have examined the
      significance of the hallmarks of physiological cell death in an effort to
      elucidate critical mechanistic elements of the cell death process. Here we
      describe our recent studies of genome digestion. Our work has centered on the
      characterization of a set of fibroblastic cell clones that vary in their ability
      to undergo genome digestion associated with physiological cell death induced by
      cytotoxic T lymphocytes (CTL) and other stimuli. Our results demonstrate that
      genome digestion is dispensable for physiological cell death and that apoptotic
      morphology is independent of genome digestion. Our data suggest further that
      apoptotic morphology is reflective of mitotic-like aspects of the cell death
      process.

PMID- 8743415
TI  - Bleb formation and F-actin distribution during mitosis and tumor necrosis factor
      induced apoptosis.
AB  - The murine cell line C3HA has been used extensively in studies of the
      cytopathology that accompanies TNF-induced cytolysis. This cell line undergoes an
      apoptic form of cell death characterized by plasma membrane blebbing and
      cytoplasmic boiling. Since plasma membrane blebs also appear on C3HA cells during
      mitosis, in this report we have compared these blebs with those that appear
      during apoptosis to determine whether they represent related structures. Our
      results reveal several differences. During mitosis, the blebs that appear are
      smaller and more heterogeneous in size than are those that appear during
      apoptosis. In addition, during mitosis bleb formation is preceded by the
      appearance of microvilli on the cell surface. No microvilli are observed during
      apoptosis. The staining pattern with rhodamine phalloidin also differed between
      mitotic and apoptic blebs, indicating a difference in their content of f-actin.
      The blebs that form during mitosis stained in a bright, uniform manner,
      suggesting an association with f-actin. In contrast, apoptic blebs were stained
      only at their base, the bleb itself being devoid of f-actin-associated staining.
      This difference may help explain why mitotic blebs are reintegrated into the cell
      surface, while the blebs that form during apoptosis are not.

PMID- 8743416
TI  - Dendritic morphology and its effects on the amplitude and rise-time of synaptic
      signals in hippocampal CA3 pyramidal cells.
AB  - Detailed anatomical analysis and compartmental modeling techniques were used to
      study the impact of CA3b pyramidal cell dendritic morphology and hippocampal
      anatomy on the amplitude and time course of dendritic synaptic signals. We have
      used computer-aided tracing methods to obtain accurate three-dimensional
      representations of 8 CA3b pyramidal cells. The average total dendritic length was
      6,332 +/- 1,029 microns and 5,062 +/- 1,397 microns for the apical and basilar
      arbors, respectively. These cells also exhibited a rough symmetry in their
      maximal transverse and septotemporal extents (311 +/- 84 microns and 269 +/- 106
      microns). From the calculated volume of influence (the volume of the neuropil
      from which the dendritic structures can receive input), it was found that these
      cells show a limited symmetry between their proximal apical and basilar dendrites
      (2.1 +/- 1.2 x 10(6) microns 3 and 3.5 +/- 1.1 x 10(6) microns 3, respectively).
      Based upon these data, we propose that the geometry of these cells can be
      approximated by a combination of two cones for the apical arbor and a single cone
      for the basilar arbor. The reconstructed cells were used to build compartmental
      models and investigate the extent to which the cellular anatomy determines the
      efficiency with which dendritic synaptic signals are transferred to the soma. We
      found that slow, long lasting signals show only approximately a 50% attenuation
      when they occur in the most distal apical dendrites. However, synaptic transients
      similar to those seen in fast glutamatergic transmission are transferred much
      less efficiently, showing up to a 95% attenuation. The relationship between the
      distance along the dendrites and the observed attenuation for a transient is
      described simply by single exponential functions with parameters of 195 and 147
      microns for the apical and basilar arbors respectively. In contrast, there is no
      simple relation that describes how a transient is attenuated with respect to
      these cells' stratified inputs. This lack of a simple relationship arises from
      the radial orientation of the proximal apical and basilar dendrites. When
      combined, the anatomical and modeling data suggest that a CA3b cell can be
      approximated in three dimensions as the combination of three cones. The amplitude
      and time-course for a synaptic transient can then be predicted using two simple
      equations.

PMID- 8743417
TI  - Ultrastructural study of the granule cell domain of the cochlear nucleus in rats:
      mossy fiber endings and their targets.
AB  - The principal projection neurons of the cochlear nucleus receive the bulk of
      their input from the auditory nerve. These projection neurons reside in the core
      of the nucleus and are surrounded by an external shell, which is called the
      granule cell domain. Interneurons of the cochlear granule cell domain are the
      target for nonprimary auditory inputs, including projections from the superior
      olivary complex, inferior colliculus, and auditory cortex. The granule cell
      domain also receives projections from the cuneate and trigeminal nuclei, which
      are first-order nuclei of the somatosensory system. The cellular targets of the
      nonprimary projections are mostly unknown due to a lack of information regarding
      postsynaptic profiles in the granule cell areas. In the present paper, we
      examined the synaptic relationships between a heterogeneous class of large
      synaptic terminals called mossy fibers and their targets within subdivisions of
      the granule cell domain known as the lamina and superficial layer. By using light
      and electron microscopic methods in these subdivisions, we provide evidence for
      three different neuron classes that receive input from the mossy fibers: granule
      cells, unipolar brush cells, and a previously undescribed class called chestnut
      cells. The distinct synaptic relations between mossy fibers and members of each
      neuron class further imply fundamentally separate roles for processing acoustic
      signals.

PMID- 8743418
TI  - Midbrain dopaminergic neurons in the mouse: computer-assisted mapping.
AB  - The dopaminergic (DA) neurons in the midbrain play a role in cognition, affect
      and movement. The purpose of the present study was to map and quantify the number
      of DA neurons in the midbrain, within the nuclei that constitute cell groups A8,
      A9 and A10, in the mouse. Two strains of mice were used; the C57BL/6 strain was
      chosen because it is commonly used in neurobiological studies, and the FVB/N
      strain was chosen because it is used frequently in transgenic studies. DA neurons
      were identified, in every fifth 20-microns-thick coronal section, using an
      antibody against tyrosine hydroxylase. Cell locations were entered into a
      computer imaging system. The FVB/N strain has 42% more midbrain DA neurons than
      the C57BL/6 strain; on one side of the brain there were 15,135 +/- 356 neurons
      (mean +/- S.E.M.) in the FVB/N strain, and 10,645 +/- 315 neurons in the C57BL/6
      strain. In both strains, approximately 11% of the neurons were located in nucleus
      A8 (the DA neurons in the retrorubral field), 38% in nucleus A9 (the DA neurons
      in the substantia nigra pars compacta, pars reticulata, and pars lateralis), and
      51% in nucleus A10 (the DA neurons in midline regions such as the ventral
      tegmental area, central linear nucleus, and interfascicular nucleus). The number
      of midbrain DA cells, and their distribution within the three nuclear groups, is
      discussed with respect to findings in other species.

PMID- 8743419
TI  - Three electrophysiological classes of guinea pig sympathetic postganglionic
      neurone have distinct morphologies.
AB  - Sympathetic postganglionic neurones can be differentiated electrophysiologically
      into three classes (phasic, Ph; tonic, T; and long-afterhyperpolarising, LAH)
      based on their potassium channel expression and consequent differences in
      excitability. We tested whether neuronal morphology differs between these
      classes. Neurones in coeliac, inferior mesenteric, and lower lumbar paravertebral
      ganglia of guinea pigs were filled with biocytin during in vitro experiments in
      which electrical properties were recorded. The dimensions of somata and dendrites
      were measured in approximately equal numbers of stained neurones of each class.
      The three electrophysiological classes were distinct in terms of soma shape, soma
      size (Ph < T = LAH), total dendritic length (LAH < Ph < T) and average length of
      dendrites (LAH < Ph < T) (P < 0.0001, multivariate analysis of variance). The
      mean number of primary dendrites also differed (LAH 13, Ph 16, T 20). The
      majority of dendrites did not branch, the ratios of terminations to primary
      dendrites being 1.36 (LAH), 1.63 (Ph) and 1.81 (T). Overall, LAH neurones, with
      medium-sized somata but the smallest dendritic trees, were more distinct
      morphologically than Ph and T neurones. The morphological differences between
      classes were not dependent on differences in location. Further, there was no
      apparent relation between morphology and the pattern of synaptic input each class
      receives. The results indicate that three distinct groups of sympathetic
      postganglionic neurone exist in adult guinea pigs, although more than three
      functions are subserved by these neurones.

PMID- 8743420
TI  - Expression of insulin-like growth factor-1 (IGF-1) and IGF-binding protein 2 (IGF
      BP2) in the hippocampus following cytotoxic lesion of the dentate gyrus.
AB  - Receptor binding and gene expression of several members of the IGF gene family
      were examined in the rat brain following lesion of the hippocampal dentate gyrus
      granular cells by intradentate colchicine injection. Dentate granular cell loss
      was accompanied by extensive reactive gliosis in the lesioned hippocampus and
      damaged overlying cortex, as verified by the increase in GFAP mRNA and BS-1
      lectin binding. At 4 days post-lesion, 125I-IGF-2 binding was dramatically
      increased within the lesioned dentate gyrus and damaged overlying cortex, and
      corresponded temporally and anatomically with increased IGF-BP2 gene expression
      following the lesion. Increased IGF-BP3 gene expression was only observed in the
      overlying cortex at 10 days post-lesion, and corresponded with an increase in
      125I-IGF-1 binding at the injured surface of the cortex. Type-2 IGF receptor mRNA
      expression was reduced to background levels in the lesioned dentate gyrus,
      suggesting that IGF-BP2 was a major component of the observed increase in 125I
      IGF-2 binding. In situ hybridization also revealed a prominent increase in IGF-1
      mRNA expression by 4 days post-lesion, which was localized within the lesioned
      dentate gyrus and damaged cortical areas, and was shown to be expressed by
      microglia. While no IGF-2 mRNA expression was observed within the CNS, either
      prior to, or following the lesion, IGF-2 mRNA expression was observed in the
      choroid plexus, meningeal membranes, and in blood vessel endothelium, providing a
      potential source for the transport of IGF-2 into the CNS. In the injured CNS,
      increased IGF-BP2 expression may act to maintain or transport IGF-1 or IGF-2, as
      well as modulate the local autocrine and paracrine actions of the IGFs. Increased
      microglial IGF-1 expression following colchicine treatment correlates with the
      timing of a number of post-traumatic events within the CNS, suggesting that IGF-1
      may have a role as a neuroprotectant for surviving neurons and signal for local
      neuronal sprouting, as well as a role in reactive astrogliosis.

PMID- 8743421
TI  - Position-specific central projections of mechanosensory neurons on the haltere of
      the blow fly, Calliphora vicina.
AB  - The halteres of Dipteran insects play an important role in flight control. They
      are complex mechanosensory devices equipped with approximately 400 campaniform
      sensilla, cuticular strain gauges, which are organized into five fields at the
      base of each haltere. Despite the important role of these mechanosensory
      structures in flight, the central organization of the sensory afferents
      originating from the different field campaniforms has not been determined. We
      show here that in the blow fly, Calliphora vicina, sensory afferents from the
      campaniform fields project to the thorax in a region-specific manner. Afferents
      from different fields have different projection profiles and in addition, the
      projection pattern of afferents from different regions of the same field may show
      further variation. However, central target regions of these afferents are not
      exclusive to particular sensory fields because cells from different fields can
      possess similar projection profiles. Convergence of afferent projections is not
      limited to axons from the haltere fields, but is also observed between afferents
      originating from the haltere fields and those from serially homologous fields on
      the radial vein of the wing. Although we have not determined the specific
      cellular targets of the haltere sensory cells, the afferents of a dorsal field
      could make potential contact with at least one identified wing steering
      motoneuron that is known to be important in turning maneuvers. Our results, thus,
      provide the anatomical basis for studying how mechanosensory information encoded
      by the complex fields on the base of the haltere is mapped onto different
      functional regions within the CNS.

PMID- 8743422
TI  - Distribution of Dip-allatostatin I-like immunoreactivity in the brain of the
      locust Schistocerca gregaria with detailed analysis of immunostaining in the
      central complex.
AB  - The distribution and morphology of neurons containing allatostatin-related
      substances in the brain of the locust Schistocerca gregaria was investigated
      using an antiserum against Diploptera punctata allatostatin I (Dip-allatostatin
      I, APSGAQRLYGFGL-amide). In each brain hemisphere, about 550 neurons in the
      midbrain and 500 neurons in the optic lobe exhibit Dip-allatostatin I-like
      immunoreactivity, including about eight lateral neurosecretory cells with
      processes to the retrocerebral complex. All major brain areas except the antennal
      lobe, the mushroom body, and large parts of the lamina, are innervated by Dip
      allatostatin I-immunoreactive processes. Immunostaining in the central complex
      was studied in detail. The central complex is innervated by more than 260 Dip
      allatostatin I-immunoreactive neurons belonging to six different cell types, four
      sets of tangential neurons and two sets of columnar neurons. These neurons give
      rise to intense immunostaining in the protocerebral bridge, in several layers of
      the upper division of the central body, and in the dorsalmost layer of the lower
      division of the central body. Double-label experiments show colocalization of Dip
      allatostatin I- and serotonin-like immunoreactivities in one type of columnar and
      one type of tangential neurons of the central complex. The similar patterns of
      Dip-allatostatin I- and galanin message-associated peptide-like
      immunoreactivities result from cross-reactivity of the anti-galanin message
      associated peptide antiserum with Dip-allatostatin I. The results provide further
      insight into the anatomical and neurochemical organization of the locust central
      complex and suggest a prominent neuroactive role for Dip-allatostatin I-related
      peptides in this brain area.

PMID- 8743423
TI  - Distribution of neuromedin U-like immunoreactivity in the central nervous system
      of Rana esculenta.
AB  - The distribution of perikarya and nerve fibers containing neuromedin U-like
      immunoreactivity in the brain of Rana esculenta was determined with an antiserum
      directed toward the carboxyl terminus of the peptide. In the telencephalon,
      immunoreactive perikarya were found in the olfactory bulb, the medial septum, and
      the diagonal band. In the diencephalon, labeled perikarya were detected in the
      anterior and posterior preoptic areas, the dorsal nucleus of the hypothalamus,
      the caudal part of the infundibulum, and the posterior tuberculum. In the
      mesencephalon, immunoreactive cell bodies were found only in the laminar nucleus
      of the torus semicircularis and the anterodorsal tegmental nucleus. In the
      rhombencephalon, labeled perikarya were detected in the secondary visceral
      nucleus, the cerebellar nucleus, the central gray, and the nucleus of the
      solitary tract. Immunoreactive nerve fibers were observed in all areas of the
      brain that contained labeled perikarya. The densest accumulations were found in
      the nucleus accumbens; the dorsal part of the lateral septum; the periventricular
      region of the ventral thalamus; the lateral part of the infundibulum; the
      anterodorsal, anteroventral, posterodorsal, and posteroventral tegmental nuclei;
      and the periaqueductal region of the tegmentum. The distribution of neuromedin U
      like immunoreactivity in the frog brain was substantially different from the
      distribution described for the rodent brain.

PMID- 8743424
TI  - Rhombomere-specific origin of branchial and visceral motoneurons of the facial
      nerve in the rat embryo.
AB  - The goal of this study was to localize selectively the facial nerve branchial and
      visceral motoneurons in the rat embryo hindbrain. This was achieved by injecting
      dextran amines into the peripheral facial nerve on embryos maintained in an
      artificial cerebrospinal fluid. Sprague-Dawley rat embryos 13, 14, and 15 days
      old (E13, E14, E15) were obtained by cesarean section. Branchial motoneurons were
      first labeled at E13. They were close to the midline and migrated from rhombomere
      (r) 4 toward r5 and r6. By E15, they had migrated caudally and ventrolaterally
      into the former location of r6. Most of them had reached their "adult" position
      by E15. Another group of motoneurons, the accessory facial nucleus, was found in
      r4 at E13 and in corresponding regions at later stages. Visceral motoneurons were
      labeled from the periphery at all stages. At E13, they were mainly in r5 but also
      in r2, r3, r4, and r6. At E14, most of them had migrated laterally, and, by E15,
      they were in the prospective parvocellular reticular formation. They could be
      divided into two subgroups: a more rostral one with fibers that made loops close
      to the midline and a more caudal one with fibers that went directly to the exit.
      The findings presented here show that most branchial and visceral motoneurons of
      the facial nerve are born in different and specific rhombomeres. Interestingly,
      developmental genes are expressed specifically in these rhombomeres and could be
      involved in the genesis of the facial and superior salivatory nuclei.

PMID- 8743425
TI  - Conformational changes of smooth endoplasmic reticulum induced by brief anoxia in
      rat Purkinje cells.
AB  - Morphological changes of the smooth endoplasmic reticulum (SER) in rat cerebellar
      Purkinje cell dendrites were examined under apneic conditions for 1-5 minutes,
      induced by an incision of the diaphragm and the collapse of the lungs. The
      dendrites obtained from control rats contained a tubular network of the SER and
      hypolemmal cisterns adjacent to the plasma membrane. After a 3-5-minute apnea,
      the cytoplasm was occupied by many flattened cisterns stacked into lamellae,
      referred to as "lamellar bodies." A quantitative analysis revealed that the
      number of lamellar bodies became maximum after 3 minutes of apnea. After the
      treatment time, they increased in size by adding new cisterns to the previous
      core lamellae. This analysis also showed that the total amount of the SER
      membranes contained in a dendrite did not change during anoxia. Conformational
      changes from the tubular or hypolemmal SER to lamellar bodies during brief anoxia
      might occur through a transient and intermediate form of "fenestrated cisterns,"
      flat across the transverse plane and penetrated by many longitudinally arranged
      microtubules. We suggest that these morphological changes of the SER during brief
      anoxia are not fixation artifacts but represent a biological reaction for
      protecting against intracellular abnormalities during anoxia.

PMID- 8743426
TI  - Colocalization of calbindin D-28k, calretinin, and GABA immunoreactivities in
      neurons of the human temporal cortex.
AB  - The calcium-binding proteins calbindin D-28k (CalB) and calretinin (CalR) have
      been shown to be useful markers of neuronal subpopulations located mainly in
      layers II-III of the neocortex of a variety of species, including human. Double
      labeling immunocytochemical studies of CalB, CalR, and GABA in experimental
      animals have shown that CalB and CalR are present in separate subpopulations of
      neurons. However, there are no studies of colocalization of these calcium-binding
      proteins and GABA in the human neocortex. The principal goal of the present work
      was to investigate the degree of colocalization of these substances in layers II
      III of the human temporal neocortex, using a postembedding immunocytochemical
      method. The patterns of staining for CalB, CalR, and GABA in the human cortex
      were similar to those found in monkey neocortex. However, the degree of
      colocalization for certain combinations was different from that reported in the
      monkey and other experimental animals. A relatively large proportion of CalB- and
      CalR-immunoreactive cells (approximately 71% and 74%, respectively) were found to
      be immunoreactive for GABA. However, the degree of colocalization of CalB with
      CalR was low (between 4% and 6%). Thus, our quantitative and qualitative data
      suggest that these calcium-binding proteins are present in similar cortical
      circuits in all primates, but that in the human neocortex, there might be
      additional GABAergic and perhaps also non-GABAergic interneurons with unique
      chemical characteristics.

PMID- 8743427
TI  - A bad start for socioeconomically disadvantaged children.

PMID- 8743429
TI  - Turning CFCs into salt.

PMID- 8743428
TI  - Helping schoolchildren with asthma breathe easier: partnerships in community
      based environmental health education.
AB  - Hospitalizations and deaths attributed to asthma are increasing, and the disease
      has disproportionate impacts on children and minority populations, particularly
      African-Americans. Because asthma hospitalizations and deaths are viewed by many
      experts as preventable events, and because asthma's toll is so significant in
      economic terms, increased efforts to reverse these trends, particularly among the
      most affected groups, are warranted. Reducing exposures to airborne pollutants
      known to trigger asthma in both indoor and outdoor environments is one important
      preventive strategy. The public-private partnership effort to implement the Open
      Airways for Schools asthma management curriculum in urban elementary schools,
      with its emphasis on pollution prevention, is an example of a community-based
      effort that may help decrease the toll asthma takes on society.

PMID- 8743430
TI  - Cytokine knockouts.

PMID- 8743431
TI  - Mexican brickmaking.

PMID- 8743432
TI  - Science from the sea.

PMID- 8743433
TI  - Phytoestrogens. Friends or foes?

PMID- 8743434
TI  - Working toward a new NIOSH.

PMID- 8743435
TI  - A cleaner bill of health.

PMID- 8743436
TI  - Health effects of acid aerosols on North American children: air pollution
      exposures.
AB  - Air pollution measurements were conducted over a 1-year period in 24 North
      American communities participating in a respiratory health study. Ozone, particle
      strong acidity, sulfate, and mass (PM10 and PM2.1) were measured in all
      communities. In 20 of the communities, sulfur dioxide, ammonia, nitric acid,
      nitrous acid, and particulate nitrate were measured. The sampler was located
      centrally in the community whenever possible and samples were collected every
      other day. Concentrations of particle strong acidity, mass, sulfate, and ozone
      were highly correlated both in the region of the country defined as a high-sulfur
      source area and in the downwind transport regions. These regions of the eastern
      United States and southern Canada experienced the greatest particle strong
      acidity, sulfate, and particle mass concentrations during the spring and summer
      months (May-September). The particle strong acidity concentrations were highest
      in regions close to the high sulfur emission areas of the United States; that is,
      in the area immediately to the west of the Appalachian Plateau and west of the
      Allegheny Mountains (western Pennsylvania, eastern Ohio, and West Virginia) up
      through southern Ontario. The frequency of particle strong acidity events
      decreased with transport distance from the region of highest sulfur emissions.
      Low particle strong acidity and sulfates were found at the western and midwestern
      sites of both the United States and Canada. Substantial concentrations of nitric
      acid were found in two of the California sites as well as many sites in the
      northeastern portion of the United States. Sites selected for the epidemiologic
      study provide a range of annual mean particle strong acidity exposures from below
      the limit of detection to more than 50 nmol/m3.

PMID- 8743437
TI  - Health effects of acid aerosols on North American children: respiratory symptoms.
AB  - We examined the respiratory health effects of exposure to acidic air pollution
      among 13,369 white children 8 to 12 years old from 24 communities in the United
      States and Canada between 1988 and 1991. Each child's parent or guardian
      completed a questionnaire. Air quality and meteorology were measured in each
      community for a 1-year period. We used a two-stage logistic regression model to
      analyze the data, adjusting for the potential confounding effects of sex, history
      of allergies, parental asthma, parental education, and current smoking in the
      home. Children living in the community with the highest levels of particle strong
      acidity were significantly more likely [odds ratio (OR) = 1.66; 95% confidence
      interval (CI) 1.11-2.48] to report at least one episode of bronchitis in the past
      year compared to children living in the least-polluted community. Fine
      particulate sulfate was also associated with higher reporting of bronchitis (OR =
      1.65; 95% CI 1.12-2.42). No other respiratory symptoms were significantly higher
      in association with any of the air pollutants of interest. No sensitive subgroups
      were identified. Reported bronchitis, but neither asthma, wheeze, cough, nor
      phlegm, were associated with levels of particle strong acidity for these children
      living in a nonurban environment.

PMID- 8743439
TI  - Association between drinking water disinfection and somatic parameters at birth.
AB  - We conducted an epidemiological study in Liguria, Italy, on the association
      between somatic parameters at birth and drinking water disinfection with chlorine
      dioxide and/or sodium hypochlorite. Over 2 years (1988-1989), 676 births at two
      public hospitals, one in Genoa (548 cases) and another in Chiavari (128 cases)
      were examined and data regarding both mother and child were obtained from
      hospital records. Results indicate a higher frequency of small body length (< or
      = 49.5 cm) and small cranial circumference (< or = 35 cm) in infants born to
      mothers who drank water treated with chlorine compounds. In particular, the
      statistical analysis (by simultaneous variance analysis and Scheffe test)
      indicated that there may be an association between infants with smaller body
      length and mothers who drank water treated with chlorine dioxide [adjusted odds
      radio (OR) = 2.0; 95% CI = 1.2-3.3] or sodium hypoclorite (adjusted OR = 2.3; 95%
      CI = 1.3-4.2) and between infants with smaller cranial circumference and mothers
      who drank water treated with chlorine dioxide (adjusted OR = 2.2; 95% CI = 1.4
      3.9) or sodium hypochlorite (adjusted OR = 3.5; 95% CI = 2.1-8.5). The presence
      of neonatal jaundice is almost twice as likely (adjusted OR = 1.7; 95% CI = 1.1
      3.1) in infants whose mothers drank water treated with chlorine dioxide.

PMID- 8743438
TI  - Health effects of acid aerosols on North American children: pulmonary function.
AB  - We examined the health effects of exposure to acidic air pollution among children
      living in 24 communities in the United States and Canada. Parents of children
      between the ages of 8 and 12 completed a self-administered questionnaire and
      provided consent for their child to perform a standardized forced expiratory
      maneuver at school in 22 of these communities. Air quality and meteorology were
      measured in each community for the year preceding the pulmonary function tests.
      Forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1.0)
      measurements of 10,251 white children were examined in a two-stage regression
      analysis that adjusted for age, sex, height, weight, and sex-height interaction.
      In this study, a 52 nmol/m3 difference in annual mean particle strong acidity was
      associated with a 3.5% (95% CI, 2.0-4.9) decrement in adjusted FVC and a 3.1%
      (95% CI, 1.6-4.6) decrement in adjusted FEV1.0. The FVC decrement was larger,
      although not significantly different, for children who were lifelong residents of
      their communities (4.1%, 95% CI, 2.5-5.8). The relative odds for low lung
      function (that is, measured FVC less than or equal to 85% of predicted), was 2.5
      (95% CI, 1.8-3.6) across the range of particle strong acidity exposures. These
      data suggest that long-term exposure to ambient particle strong acidity may have
      a deleterious effect on lung growth, development, and function.

PMID- 8743440
TI  - Nitrate contamination of drinking water: relationship with HPRT variant frequency
      in lymphocyte DNA and urinary excretion of N-nitrosamines.
AB  - We studied peripheral lymphocyte HPRT variant frequency and endogenous
      nitrosation in human populations exposed to various nitrate levels in their
      drinking water. Four test populations of women volunteers were compared. Low and
      medium tap water nitrate exposure groups (14 and 21 subjects) were using public
      water supplies with nitrate levels of 0.02 and 17.5 mg/l, respectively. Medium
      and high well water nitrate exposure groups (6 and 9 subjects) were using private
      water wells with mean nitrate levels of 25 and 135 mg/l, respectively. Higher
      nitrate intake by drinking water consumption resulted in a dose-dependent
      increase in 24-hr urinary nitrate excretion and in increased salivary nitrate and
      nitrite levels. The mean log variant frequency of peripheral lymphocytes was
      significantly higher in the medium well water exposure group than in the low and
      medium tap water exposure groups. An inverse correlation between peripheral
      lymphocyte labeling index and nitrate concentration of drinking water was
      observed. Analysis of N-nitrosamine in the urine of 22 subjects by gas
      chromatography-mass spectrometry revealed the presence of N-nitrosopyrrolidine in
      18 subjects. Analysis of the mutagenicity of well water samples showed that a
      small number of the well water samples were mutagenic in the Ames Salmonella
      typhimurium test after concentration over XAD-2 resin. In conclusion, consumption
      of drinking water, especially well water, with high nitrate levels can imply a
      genotoxic risk for humans as indicated by increased HPRT variant frequencies and
      by endogenous formation of carcinogenic N-nitroso compounds from nitrate-derived
      nitrite.

PMID- 8743441
TI  - Exposure to polycyclic aromatic hydrocarbons among Dutch children.
AB  - We determined the urinary 1-hydroxypyrene (1-HP) concentration and the creatinine
      adjusted 1-HP concentration in 644 randomly selected Dutch children, aged 1-6
      years and living in five areas with roughly different levels of polycyclic
      aromatic hydrocarbons (PAHs) in soil and ambient air. The presence of other
      factors that might influence the exposure to PAHs was studied using a
      questionnaire. To evaluate the reliability of a single urinary 1-HP
      determination, measurements were repeated after 3 weeks for approximately 200
      children. The mean urinary 1-HP content of the total study population was 2.06
      nmol/l. This varied from 1.58 nmol/l in the reference area (Flevoland) to 2.71
      nmol/l in the valley of the Geul. Only indoor sources of PAHs showed a small,
      positive association with urinary 1-HP. The urinary 1-HP concentrations of
      children from the valley of the Geul were higher (p < 0.01) and those of children
      from a suburb of Amsterdam were lower (p < 0.01) than those of children from the
      reference area. The possible ambient environment-related differences were
      probably too small to be detected in the variations of the intake of PAHs from
      the daily diet. The reliability of a single 1-HP measurement was low. Similar
      results were obtained with the creatinine-adjusted data. In one neighborhood
      built on coal-mine tailings, the urinary 1-HP content in children was weakly but
      positively associated with the PAH content in the upper soil layer of the garden
      of their homes. However, this association was not found for the children from the
      other neighborhood built on coal-mine tailings and with similar PAH levels in
      soil.

PMID- 8743442
TI  - Assessment of regional cytochrome P450 activities in rat liver slices using
      resorufin substrates and fluorescence confocal laser cytometry.
AB  - Characterizing constitutive activities and inducibility of various cytochrome
      P450 isozymes is important for elucidating species and individual differences in
      susceptibility to many toxicants. Although expression of certain P450s has been
      studied in homogenized tissues, the ability to assess functional enzyme activity
      without tissue disruption would further our understanding of interactive factors
      that modulate P450 activities. We used precision-cut, viable rat liver slices and
      confocal laser cytometry to determine the regional enzyme activities of P450
      isozymes in situ. Livers from control and beta-naphthoflavone (beta NF)-treated
      rats were sectioned with a Krumdieck tissue slicer into 250-microns thick
      sections. A slice perfusion chamber that mounts on the cytometer stage was
      developed to allow for successive measurement of region-specific P450-dependent O
      dealkylation of 7-ethoxy-, 7-pentoxy-, and 7-benzyloxyresorufin (EROD, PROD, and
      BROD activity, respectively) in the same liver slice. Images of the accumulated
      fluorescent resorufin product within the tissue were acquired using a confocal
      laser cytometer in confocal mode. As expected, slices isolated from beta NF
      treated rats showed high levels of centrilobular EROD activity compared to slices
      from control rats, whereas PROD and BROD activities remained at control levels.
      These techniques should allow for the accurate quantification of regional and
      cell-specific P450 enzyme activity and, with subsequent analysis of the same
      slice, the ability to correlate specific P450 mRNAs or other factors with
      enzymatic activity. Moreover, these techniques should be amenable to examination
      of similar phenomena in other tissues such as lung and kidney, where marked
      heterogeneity in cellular P450 expression patterns is also known to occur.

PMID- 8743443
TI  - A yeast estrogen screen for examining the relative exposure of cells to natural
      and xenoestrogens.
AB  - Xenoestrogens, such as o,p'-DDT and octyl phenol (OP), have been associated with
      reproductive abnormalities in various wildlife species. Xenoestrogens mimic the
      natural estrogen 17 beta-estradiol and compete for binding to the estrogen
      receptor. Even though the affinity of o,p'-DDT and OP for the estrogen receptor
      is approximately 1000-fold lower than 17 beta-estradiol, the actions of
      xenoestrogens could be enhanced if their bioavailability in serum were greater
      than 17 beta-estradiol. To test this hypothesis, the yeast estrogen screen (YES)
      was created by expressing human estrogen receptor (hER) and two estrogen response
      elements (ERE) linked to the lacZ gene. The beta-galactosidase activity of the
      YES system was significantly increased after treatment with 17 beta-estradiol or
      the xenoestrogens diethylstilbestrol (DES), o,p'-DDT, and OP but not with
      vehicle, antiestrogen ICI 164,384, dexamethasone, or testosterone. To determine
      whether serum proteins affected the bioavailability of natural estrogens compared
      to xenoestrogens, albumin, sex hormone binding globulin (SHBG), or charcoal
      stripped serum were added to the YES system and beta-galactosidase activity
      assayed. Albumin and SHBG decreased beta-galactosidase activity in the presence
      of estradiol to a greater extent than DES, o,p'-DDT, and OP. Human and alligator
      charcoal-stripped serum were also effective at selectively reducing beta
      galactosidase activity in the presence of estradiol compared to xenoestrogens.
      Human serum was more effective than alligator serum in reducing beta
      galactosidase activity in the presence of xenoestrogens, indicating that serum
      may serve as a biomarker for sensitivity to xenoestrogens. Selective binding of
      17 beta-estradiol by proteins in serum indicates that certain xenoestrogens may
      exert greater estrogenicity than originally predicted. The estrogenic potency of
      a compound involves its binding affinity, bioavailability in serum, and
      persistence in the environment. Our data demonstrate the utility of the YES
      system for identifying and characterizing environmental estrogens.

PMID- 8743445
TI  - Homer William Smith. January 2, 1895-March 25, 1962. Introduction.

PMID- 8743444
TI  - Synergistic effect of 2,2',4,4',5,5'-hexachlorobiphenyl and 2,3,7,8
      tetrachlorodibenzo-p-dioxin on hepatic porphyrin levels in the rat.
AB  - We studied the effect of polychlorinated biphenyls (PCBs) on hepatic porphyrin
      accumulation in female Sprague-Dawley rats by feeding them diets containing
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,2',4,4',5,5'-hexachlorobiphenyl
      (PCB 153), 2,3,3',4,4',5-hexachlorobiphenyl (PCB 156), 3,3',4,4',5
      pentachlorobiphenyl (PCB 126), or combinations of the single PCB congeners with
      TCDD for 13 weeks. A dose-dependent increase in hepatic porphyrin accumulation
      occurred after TCDD, PCB 126, or PCB 156 administration, reaching maximal levels
      of about twice control values. The lowest dose levels for which a significant
      increase in hepatic porphyrin accumulation was found were 0.7 microgram TCDD/kg
      diet, 50 micrograms PCB 126/kg diet, or 6 mg PCB 156/kg diet. These doses are
      equivalent to 47 ng TCDD/kg/day, 3.2 micrograms PCB 126/kg/day, and 365
      micrograms PCB 156/kg/day. Relative potencies for hepatic porphyrin accumulation,
      using TCDD as a reference, ranged from 0.015 to 0.06 for PCB 126 and from 0.0001
      to 0.0003 for PCB 156. CYP1A2 activities significantly correlated with hepatic
      porphyrin levels, with coefficients of 0.629, 0.483, or 0.808 for TCDD, PCB 126,
      or PCB 156, respectively. Administration of PCB 153 alone did not result in
      hepatic porphyrin accumulation. Co-administration of PCB 153 and TCDD revealed a
      strong synergistic effect on porphyrin accumulation (about 800 times control
      levels). This synergistic effect was significant in rats fed diets containing any
      combination of PCB 153 with TCDD. Uroporphyrin III and heptacarboxylic porphyrin
      were accumulated in porphyrinogenic livers. These results suggest that TCDD
      induction of CYP1A2 may be involved, leading to oxidation of uroporphyrinogen III
      to uroporphyrin III, in combination with an increase in delta-aminolevulinic acid
      synthetase induced by PCB 153. Under porphyrinogenic conditions, an inhibitor of
      CYP1A2 activity may also be formed. The interactive effects on porphyrin
      accumulation after co-administration of dioxinlike and non-dioxinlike compounds
      may have significant implications for the risk assessment of these chemicals.

PMID- 8743446
TI  - Homer W. Smith: the nephrologist.

PMID- 8743447
TI  - Homer W. Smith: the humanist.

PMID- 8743448
TI  - Homer Smith: an eclectic mentor.

PMID- 8743449
TI  - Contributions of clinical medicine to renal physiology.
AB  - The strong influence of clinical medicine on the development of renal physiology
      in the 20th century is a natural consequence of the striking disorders imposed by
      disease on the volume and composition of the fluids of the body. Clinicians well
      grounded in physiology were able to seize unusual opportunities provided by sick
      patients to elucidate principles of homeostatic control applicable to health as
      well as to disease. Three examples of such contributions, primarily originating
      at the bedside, are discussed: the role of potassium in metabolic alkalosis, the
      function of the parathyroid glands as exemplified by the syndrome of
      hyperparathyroidism, and the discovery of a humoral factor, distinct from
      parathyroid hormone, that may regulate phosphate excretion by the kidneys.

PMID- 8743450
TI  - Evolutionary aspects of renal function.
AB  - In his hypothesis of the evolution of renal functions Homer Smith proposed that
      the formation of glomerular nephron and body armor had been adequate for the
      appearance of primitive vertebrates in fresh water and that the adaptation of
      homoiotherms to terrestrial life was accompanied by the appearance of the loop of
      Henle. In the current paper, the increase in the arterial blood supply and
      glomerular filtration rate and the sharp elevation of the proximal reabsorption
      are viewed as important mechanisms in the evolution of the kidney. The presence
      of glomeruli in myxines and of nephron loops in lampreys suggests that fresh
      water animals used the preformed glomerular apparatus of early vertebrates, while
      mechanisms of urinary concentration was associated with the subdivision of the
      kidney into the renal cortex and medulla. The principles of evolution of renal
      functions can be observed at several levels of organizations in the kidney.

PMID- 8743451
TI  - Mechanism of fluid secretion common to aglomerular and glomerular kidneys.
AB  - Isolated renal proximal tubules of sea water fish net secrete fluid in vitro. The
      principal electrolytes in secreted fluid are Na, Cl, Mg and S. Transepithelial
      voltages may be lumen-negative or -positive by a few millivolts, and
      transepithelial resistances are low partly due to high paracellular Na and Cl
      permeabilities. Transepithelial electrochemical potentials indicate secretion of
      Mg into the tubule lumen by active transport. As Mg concentration in secreted
      fluid rises, Na concentration falls. Surprisingly, these observations of fluid
      secretion are made in glomerular and aglomerular proximal tubules, suggesting a
      fundamental mechanism common to both. Central to this commonality appears to be
      their behavior as open Donnan systems. Mg actively secreted into the tubule lumen
      from which it cannot diffuse back into the peritubular medium causes the
      transepithelial secretion of diffusible Na and Cl. Water follows by osmosis.
      Since there is flow out of the distal end of the tubule Donnan equilibrium is not
      attained. Instead, a dynamic Donnan system is maintained, driven by active
      transport of Mg. A mathematical model of tubular electrolyte and fluid secretion
      confirms the operation of this open, dynamic Donnan system in aglomerular and
      glomerular proximal tubules.

PMID- 8743452
TI  - Comparative aspects of renal urate transport.
AB  - Urate is the major excretory end product of nitrogen metabolism in birds, most
      reptiles, and some amphibians and undergoes net secretion by the renal tubules.
      Secretion has been studied in isolated renal proximal tubules from reptiles and
      birds. Net secretion is influenced by passive backflux between the tubule cells
      that varies with perfusion rate. Transepithelial transport from bath to lumen
      involves uptake into the cells against an electrochemical gradient at the
      basolateral membrane and movement from the cells to the lumen down an
      electrochemical gradient. However, the apparent permeability of the basolateral
      membrane to urate is much higher than that of the luminal membrane. Transport
      into the cells at the basolateral membrane is dependent, in part, on the presence
      of filtrate (or an appropriate substitute) in the lumen. Because reptilian and
      avian nephrons filter intermittently, passive back-diffusion between the cells,
      high permeability of the basolateral membrane, and dependence of basolateral
      transport on luminal perfusion may prevent accumulation of urate in the cells or
      lumens of nonfiltering nephrons. In reptiles, basolateral transport is Na
      independent but K-dependent and may involve countertransport for some unknown
      anion. In birds, this transport step, which is Na- and K-dependent, may occur by
      two separate systems, one involving counter-transport for an unknown anion and
      the other involving the general tertiary transport process for other organic
      anions such as PAH. It has not yet been possible to demonstrate that transport
      from the cells to the lumen down an electrochemical gradient is carrier-mediated
      in either reptiles or birds and some other process may be involved.

PMID- 8743453
TI  - The rectal gland of Squalus acanthias: a model for the transport of chloride.
AB  - The rectal gland of the spiny dogfish shark, Squalus acanthias, secretes chloride
      by a furosemide sensitive process that has been termed "secondary active."
      Chloride enters the cell across the basolateral cell membrane via the
      sodium:potassium:2 chloride cotransporter. The energy for this electroneutral
      uptake step is provided by the electrochemical gradient for sodium directed into
      the cell. This is maintained by Na-K-ATPase present in the basolateral cell
      membrane. Present as well in the basolateral cell membrane is a potassium
      conductance that permits potassium to exit passively. Chloride leaves the cell
      across the luminal membrane via a chloride conductance closely similar to CFTR.
      The rectal gland is thus a model for the mechanism of secondary active chloride
      transport utilized by various epithelial organs throughout the vertebrate
      kingdom. This report reviews the humoral agents that regulate the secretion of
      chloride by the rectal gland and the intracellular mechanisms that mediate it.
      CNP, released from the heart in response to a volume stimulus, causes the release
      of VIP from nerves within the gland and together with VIP directly activates the
      rectal gland cell.

PMID- 8743454
TI  - Cellular and molecular biology of chloride secretion in the shark rectal gland:
      regulation by adenosine receptors.
AB  - The rectal gland of the dogfish shark (Squalus acanthias) is a sodium chloride
      secreting epithelial organ whose function was discovered in 1959 by Wendell
      Burger. The gland, composed of homogenous tubules of a single cell type, is an
      important model for secondary active chloride transport. Hormonal stimulation of
      chloride secretion in this system activates asymetrically arranged transport
      proteins (apical cAMP-activated CFTR-like Cl- channels, basolateral Na/K/2Cl
      cotransporters, Na/K-ATPase activity, and K+ channels). Five receptors, hormones,
      and membrane proteins of the shark rectal gland involved in chloride secretion
      have been cloned recently. Because the intact gland can be perfused via a single
      artery and vein, it has been possible to examine precisely the metabolic
      regulation of chloride transport by endogenous adenosine. Rectal gland cells have
      a high density of both stimulatory A2 type and inhibitory A1 type adenosine
      receptors. When stimulated by secretagogues, chloride secretion and venous
      adenosine concentrations increase in parallel, with chloride secretion increasing
      from approximately 150 to 2100 microEq/hr/g, and adenosine concentrations
      increasing from approximately 5 to approximately 890 nM. This work of ion
      transport is accompanied by a marked fall in intracellular ATP activity and a
      rise in both intracellular AMP and adenosine activity. Agents that prevent the
      interaction of endogenous adenosine with extracellular receptors significantly
      increase the chloride transport response to secretagogues. When chloride
      transport is inhibited by blocking the Na/K/2Cl cotransporter with bumetanide,
      both adenosine release and chloride secretion fall to basal values. We recently
      cloned a unique adenosine receptor subtype that is distinct from previously
      cloned mammalian adenosine receptors. Because of its highly specialized function,
      single cell type, and simple vascular system, the shark rectal gland is an ideal
      model system for examining the metabolic regulation of chloride secretion by
      adenosine receptors.

PMID- 8743455
TI  - Chloride cells and osmoregulation.
AB  - The chloride cells of the gill secretory epithelium of fish that make the
      transition from fresh water to sea water adapt to the increased salinity by
      responding to a rapid signal that stimulates chloride secretion. In this paper,
      data are presented supporting the view that the transient increase in plasma
      osmolarity that can be measured during the transition is responsible for the
      stimulation of chloride secretion. A maximal increase of 65 mOsm in the plasma of
      Fundulus heteroclitus (the killifish) was found during acclimation to sea water.
      Similar or greater increases of osmolarity induced by mannitol on the basolateral
      side of isolated opercular epithelial membranes of the same species of fish
      containing great numbers of chloride cells produced stimulation of chloride
      secretion detected as the short circuit current. The shrinkage of the chloride
      cell activates the Na-K-2Cl cotransporter, and the Na/H exchanger and requires
      the integrity of apical chloride channels and normal levels of Ca. A Cl/HCO3
      exchanger did not participate in this osmotic response to higher salinity.
      Chloride cell volume responses to osmolarity were studied with imagine and
      quantitative optics.

PMID- 8743456
TI  - Trapping of 134CS+ in frog skin epithelium as a function of short circuit
      current.
AB  - In the sodium/potassium pump of the isolated frog skin epithelium, 134CS+ can to
      a certain degree replace potassium. If 134CS+ in almost a carrier-free amount is
      added to the solution bathing the inside of the frog skin in an Ussing chamber,
      there will be an uptake of 134 CS+ into the epithelium cells which is
      proportional to the short circuit current. Transepithelial flux of 134CS+ in
      leaky epithelia, for instance small intestine and frog skin glands, indicates a
      paracellular pathway. The consequences of these findings for the recycling-theory
      are discussed.

PMID- 8743457
TI  - Stability and leakiness: opposing challenges to the glomerulus.
AB  - The complex architecture of the glomerular tuft is stabilized by several
      mechanisms. The basic system consists of the GBM and the mesangium maintaining
      the branching pattern of the capillary network. Superimposed are the podocytes,
      which appear to take effect by two mechanisms. First, podocytes contribute to the
      stabilization of the capillary folding pattern by supporting the angles between
      neighboring capillaries. Second, podocyte foot processes fixed to the outer
      aspect of the GBM probably function as contractile patches counteracting the
      elastic distension of the GBM. Simultaneously, the pattern of foot process
      interdigitation underlies the elaboration of a filtration slit and is thus
      pivotal for the high hydraulic permeability and the specificity of the glomerular
      filter. The loss of this pattern-commonly termed "foot process effacement" or
      "foot process fusion"-is frequently found in pathological situations and results
      in a decrease in permeability and impairment in specificity. On the other hand,
      foot process effacement is associated with prominent hypertrophy of the
      contractile apparatus of podocytes, suggesting an increased ability to generate
      forces counteracting capillary expansion. Thus, foot process effacement appears
      as an adaptive change in podocyte phenotype giving priority to the support
      function of podocytes for the prize of reducing the specific permeability.

PMID- 8743458
TI  - Cell-matrix interactions in the glomerular mesangium.
AB  - Specific interactions between cells and components of the surrounding
      extracellular matrix (ECM) or underlying basement membrane have been shown to
      modulate cell behavior, including cellular responses to soluble regulator
      molecules. In addition to the long-recognized role of such interactions in cell
      localization, anchoring and differentiation during embryogenesis, they are also
      involved in diverse processes such as maintenance of tissue integrity, response
      of cells to mechanical stress, inflammatory response, wound healing, tumor cell
      growth and metastasis as well as apoptosis. Over the last several years, evidence
      has been reported that extensive "cross-talk" between glomerular mesangial cells
      (MCs), ECM molecules and soluble mediator substances also affects the
      proliferative and synthetic phenotype of MCs. This is likely to be relevant for
      the behavior of MCs during embryonic development, tissue repair and disease
      processes of glomeruli. The potential biologic and clinical relevance of cell
      matrix interactions in the glomerulus makes their elucidation a challenging goal
      in current kidney research. In this brief review, we present selected aspects of
      recent investigations concerning the mesangial matrix and its interactions with
      MCs. In addition to results from cell culture studies, descriptive findings on
      abnormalities of the ECM and their potential role for the altered MC behavior in
      glomerular disease will also be discussed.

PMID- 8743459
TI  - Roles of the mesangium in glomerular function.
AB  - Among the multiple functions of the mesangial cell in glomerular physiology and
      pathophysiology, those of structural support of the capillary network, of
      participation in filtration regulation and in glomerular injury have attracted
      considerable interest. These roles are supported by studies with anti-Thy 1.1
      antibody induced mesangiolysis in rats and by genetic knockout experiments of
      PDGF or PDGF-receptors in mice. These mice show a lack of mesangial cell
      development and a concomitant failure to establish a glomerular capillary
      network. Micropuncture experiments in the rats with mesangiolysis also provide
      support for a role of mesangial cells in the regulation of glomerular filtation.
      Numerous studies have established a contribution of mesangial cells to
      immunological and non-immunological injury in the glomerulus. Under many
      conditions this involves the recruitment and activation of macrophages, which
      require generation of chemotactic peptides and expression of adhesion molecules.
      Stimulation of mesangial cells with immune complexes and proinflammatory
      cytokines such as TNF-alpha or IL-1 results in the release of chemokines and in
      the appearance of adhesion molecules on the mesangial cells. The generation of
      reactive oxygen species appears to play a major role in this context and
      involves, at least in part, the activation of the transcription factor NF-kappa
      B. These results point toward mesangial cells as important participants in
      glomerular injury.

PMID- 8743460
TI  - Mechanisms of fluid secretion by polycystic epithelia.
AB  - We have sought to determine the mechanisms driving fluid secretion by the cystic
      epithelium in autosomal dominant polycystic kidney disease (ADPKD). We have
      performed in vitro experiments on intact cysts dissected from discarded ADPKD
      kidneys, on monolayers of cells cultured from the cystic epithelium and on
      microcysts clonally derived from single cultured cells. These preparations absorb
      fluid in the control state but secrete fluid in response to native cyst fluid, to
      adenylate cyclase agonists and to permeant analogues of cAMP. Measurements of
      short-circuit current and transepithelial voltage in the monolayers indicate that
      anion secretion must drive the fluid secretion. Fluid secretion by the intact
      cysts was inhibited by basolateral application of ouabain but not by apical
      application. The effect of ouabain on fluid secretion and short-circuit current
      in the monolayers followed the same pattern. Thus the functional Na,K-ATPase
      enzyme complex is located only in the basolateral membrane of the cystic cells
      and serves to maintain the transmembrane chemical and electrical gradients that
      drive anion secretion by other transport mechanisms. Fluid secretion and short
      circuit current in the cultured monolayers was inhibited by the basolateral
      application of the Na-K-2Cl cotransporter inhibitors, bumetanide and furosemide,
      and by apical application of the chloride channel blocker, diphenylamine-2
      carboxylate (DPC). These data suggest that chloride is the anion that is actively
      secreted. Preliminary experiments utilizing the monolayers and the microcysts and
      measuring cell chloride concentration and chloride efflux across the apical
      membrane support this conclusion. Other preliminary data indicate that the cystic
      fibrosis transmembrane conductance regulator is present in the apical membrane.
      Thus active chloride transport generates fluid secretion by the cystic
      epithelium.

PMID- 8743461
TI  - Surface membrane polarity of proximal tubular cells: alterations as a basis for
      malfunction.
AB  - The surface membrane of proximal tubular cells is organized into distinct apical
      and basolateral membrane domains. The establishment and maintenance of these
      biochemically, structurally and physiologically distinct domains involves a multi
      stage process involving cell-cell, cell-ECM interactions, and polarized targeting
      mechanisms. Ischemia, via cellular ATP depletion, results in a series of
      structural, biochemical and functional alterations that lead to loss of proximal
      tubular cell surface membrane polarity. Of central importance is the rapidly
      occurring, duration-dependent disruption and dissociation of the actin
      cytoskeleton and associated surface membrane structures. This results in numerous
      cellular alterations including loss of cell-cell contact, cell-extracellular
      matrix adhesion and surface membrane polarity. Redistribution of surface membrane
      proteins and lipids into the alternate domain results in the cells inability to
      function properly. Repair of these disorders involves re-establishment of the
      actin cytoskeleton and apical and basolateral surface membrane domains. Recent
      information indicates growth factors may play a role in hastening this repair
      process.

PMID- 8743462
TI  - Direct and indirect cost of urea excretion.
AB  - Urea, the major end product of protein metabolism in mammals, is the most
      abundant solute in the urine. Urea excretion is thought to result from filtration
      curtailed by some passive reabsorbtion along the nephron. This reabsorption is
      markedly enhanced by vasopressin and slow urinary flow rate (V), the fraction of
      filtered urea excreted in the urine (FEurea) falling from approximately 60% at
      high V to only approximately 20% at low V. In concentrated urine, normal urea
      excretion can be maintained only if urea filtration is elevated. This can be
      achieved by increasing plasma urea concentration (Purea) and/or GFR. We have
      shown that both parameters do increase when normal rats are submitted to chronic
      alterations in the water intake/vasopressin axis within the normal range of
      physiologic regulation. This situation is very similar to that observed after
      alterations in protein intake. In both cases more urea needs to be filtered,
      either because more of it has to be excreted, or because the efficiency of its
      excretion is reduced. A common mechanism is proposed to explain the rise in GFR
      observed in the two situations. In summary, our studies demonstrate that the
      antidiuretic effects of vasopressin are responsible for a significant elevation
      of GFR. This GFR adaptation limits the rise in Purea, a favorable effect because
      urea is not as harmless as usually thought. However, this hyperfiltration might
      have deleterious consequences in diseased kidneys.

PMID- 8743463
TI  - Biochemical heterogeneity of arginine metabolism along kidney proximal tubules.
AB  - By using an in vitro single tubule micromethod of high specificity, in four
      different species of mammals it has been observed that (a) arginine synthesis
      from citrulline (arginine synthase activity, E.C. 6.3.4.5 and E.C. 4.3.2.1) is
      restricted to the early portions of proximal convoluted tubules, whereas (b) urea
      production from arginine (arginase activity, E.C. 3.5.3.1.) is present mainly in
      the cortical (CPST) and even more in the outer medullary (OSPST) portions of
      straight proximal tubules. The data suggest that (a) in early PCT cells, the
      citrulline reabsorbed from glomerular filtrate is converted into arginine, which
      in turn crosses peritubular cell membranes together with reabsorbed arginine, and
      (b) the urea formed in CPST and OSPST cells might passively diffuse into the
      luminal fluid entering Henle's loops. Such urea secretion might contribute to
      sustain the process of urea recycling in kidney medulla and thereby participate
      in the mechanism of urine concentration.

PMID- 8743464
TI  - Active urea transport in the rat inner medullary collecting duct: functional
      characterization and initial expression cloning.
AB  - Active transport of urea has been proposed to exist in the inner medullary
      collecting duct (IMCD) of low-protein fed mammals for over 30 years. We perfused
      IMCD subsegments from rats fed a standard (18%) or a low (8%) protein diet and
      tested for the presence of active urea transport. We found no active urea
      transport in terminal IMCDs, regardless of diet. In initial IMCDs from rats fed
      18% protein or fed 8% protein for one to two weeks, we again found no active urea
      transport. However, in rats fed 8% protein for three to four weeks, we found
      significant net urea reabsorption. This active urea reabsorption was inhibited
      when Na+, K(+)-ATPase activity was inhibited by adding 1 mM ouabain or removing
      bath potassium, suggesting a secondary active transport process. Removing sodium
      from the perfusate completely inhibited net urea reabsorption, demonstrating that
      this active urea transport is dependent upon the presence of sodium in the tubule
      lumen. Unlike the facilitated urea transporter, the active urea transporter was
      not inhibited by phloretin nor stimulated by vasopressin, suggesting that it is a
      distinct transport protein. To test this hypothesis, we size-separated poly(A)(+)
      RNA prepared from inner medullae of rats fed 8% protein for three weeks and
      injected it into Xenopus laevis oocytes. RNA from a 4.4 to 8.4 kb size fraction
      increased urea permeability fourfold compared to water-injected oocytes or
      injecting RNA from other size-fractions. We conclude that feeding rats a low
      protein diet for three weeks induces the expression of an unique, secondary
      active, sodium-dependent urea transporter whose cDNA is between 4.4 and 8.4 kb in
      size. In addition, our results suggest that it will be possible to clone the cDNA
      for this sodium-urea cotransporter by expression in Xenopus laevis oocytes.

PMID- 8743465
TI  - Structure, regulation and physiological roles of urea transporters.
AB  - Urea is the major constituent of the urine and the principal means for disposal
      of nitrogen derived from amino acid metabolism. Specialized phloretin-inhibitable
      urea transporters are expressed in kidney medulla and play a central role in urea
      excretion and water balance. These transporters allow accumulation of urea in the
      medulla and enable the kidney to concentrate urine to an osmolality greater than
      systemic plasma. Recently, expression cloning with Xenopus oocytes has led to the
      isolation of a novel phloretin-inhibitable urea transporter (UT2) from rabbit,
      and subsequently from rat kidney. UT2 from both species has the characteristics
      of the phloretin-sensitive urea transporter previously defined in kidney by in
      vitro perfused tubule studies. Based on these advances, Ripoche and colleagues
      cloned a homologous urea transporter (HUT11) from erythrocytes. UT2 and HUT11
      predict 43 kDa polypeptides and exhibit 64% amino acid sequence identity. Since
      regulation of urea transport in the kidney plays an important role in the
      orchestration of the antidiuretic response, we have studied the regulation of
      urea transporter in rat kidney at the mRNA level. On Northern blots probed at
      high stringency, rat UT2 hybridized to two transcripts of 2.9 kb and 4.0 kb,
      which have spatially distinct distributions within the kidney. Northern analysis
      and in situ hybridization of kidneys from rats maintained at different
      physiologic states revealed that the 2.9 and 4.0 kb transcripts are regulated by
      separate mechanisms. The 4 kb transcript was primarily responsive to changes in
      the dietary protein content, whereas the 2.9 kb transcript was highly responsive
      to changes in the hydration state of the animal. We propose that the two UT2
      transcripts are regulated by distinct mechanisms to allow optimal fluid balance
      and urea excretion.

PMID- 8743466
TI  - Potassium transport: from clearance to channels and pumps.
AB  - Potassium (K) homeostasis depends on the separate and interrelated regulation of
      K distribution between the intra- and extra-cellular fluid compartments and
      adequate renal excretion. This brief review focuses on the regulation of internal
      K distribution and the renal mechanisms of K handling. Based on clearance,
      micropuncture, and microperfusion studies, a large body of evidence supports the
      view that normally, renal secretion of K determines excretion and that the
      principal tubule cells in the initial and cortical collecting tubule secrete K,
      whereas K reabsorption may occur in intercalated cells. Studies of the
      electrochemical driving forces, of intracellular ion activities, the
      characterization of several ATPases, and patch clamp investigations have provided
      insight into the role of pumps and channels in those tubule cells that regulate K
      secretion and reabsorption.

PMID- 8743467
TI  - Diversity and regulation of amiloride-sensitive Na+ channels.
AB  - Amiloride-sensitive Na+ channels play a vital role in many important
      physiological processes such as delineation of the final urine composition,
      sensory transduction, and whole-body Na+ homeostasis. These channels display a
      wide range of biophysical properties, and are regulated by cAMP-mediated second
      messenger systems. The first of these channels has recently been cloned. This
      cloned amiloride-sensitive Na+ channel is termined ENaC (Epithelial Na+ Channel)
      and, in heterologous cellular expression systems, displays a single channel
      conductance of 4 to 7 pS, a high PNa/PK (> 10), a high amiloride sensitivity
      (Ki(amil) = 150 nM), and relatively long open and closed times. ENaC may form the
      core conduction element of many of these functionally diverse forms of Na+
      channel. The kinetic and regulatory differences between these channels may be
      due, in large measure, to unique polypeptides that associate with the core
      element, forming a functional channel unit.

PMID- 8743468
TI  - The electroneutral Na(+)-(K+)-Cl- cotransport family.
AB  - Recently the molecular identification of the major electroneutral sodium
      potassium-chloride entry mechanisms present on apical membranes of distal nephron
      segments of the mammalian kidney, on basolateral membranes of many non-renal
      epithelial cells and on certain non-epithelial tissues has been achieved. These
      transporters represent a major pathway for cellular uptake of chloride critical
      for chloride absorptive and secretory processes and for cell volume regulation
      following cell shrinkage. In the mammalian kidney, these sodium-coupled chloride
      cotransporters represent the major target sites for clinically useful diuretics
      including the "loop" diuretics [furosemide (Lasix) and bumetanide (Bumex)] and
      thiazides (such as, chlorothiazide, hydrochlorothiazide and metolazone). Although
      these Na-(K)-Cl cotransporters exhibit functional and pharmacological
      differences, they clearly evolved from a common ancestral gene and thus form a
      new gene family. This information is already advancing our understanding of the
      evolution, structure and function of these transporters both in renal handling of
      sodium and in hypertension.

PMID- 8743469
TI  - cAMP-regulated trafficking of epitope-tagged CFTR.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a
      phosphorylation-activated chloride channel responsible for cAMP-induced Cl
      secretion across the apical membranes of epithelial cells. To optimize its
      detection in membrane localization studies, we tagged CFTR with epitope sequences
      at the carboxy terminus or in the fourth external loop. The function of six
      different tagged-CFTRs was tested in two different physiological assays. CFTRs
      containing the M2 epitope responded to cAMP, whereas cells expressing CFTR with
      the hemagglutinin HA tag showed little or no cAMP response. Using CFTR tagged in
      the fourth external loop, we demonstrate that cAMP activation using forskolin
      results in an increase in CFTR in the plasma membrane of HeLa cells. Forskolin
      inhibited CFTR endocytosis, and this contributes to the increase in cell surface
      CFTR expression. Our results indicate that regulation of cell surface CFTR
      contributes to the increase in plasma membrane Cl conductance evoked by cAMP
      stimulation.

PMID- 8743470
TI  - Renal secretion of organic anions and cations.
AB  - The renal proximal tubule actively transports charged, potentially toxic
      xenobiotics from blood to lumen. Basolateral uptake of organic anions is
      indirectly coupled to the sodium gradient through Na-dicarboxylate cotransport
      and dicarboxylate-organic anion exchange. Upon entry, a significant fraction of
      intracellular organic anion is sequestered within vesicles. Disruption of the
      cellular microtubular network can lead to both diminished vesicular movement and
      reduced transepithelial secretion. Luminal efflux of organic anions is
      energetically downhill, but carrier mediated. Both anion exchange and potential
      driven transport are present, but neither completely accounts for transport from
      cell to lumen. For organic cations, basolateral entry is downhill via potential
      driven facilitated diffusion. Intracellular sequestration of organic cations in
      vesicles is substantial, but its role in secretion is uncertain. Multiple
      carriers are available to drive organic cations uphill into the tubular lumen.
      The classical system indirectly taps the energy of the luminal Na gradient to
      drive organic cation efflux via Na(+)-H+ and proton-organic cation exchange. In
      addition, the multidrug resistance ATPase can pump organic cations into the
      tubular lumen. Thus, although much detailed information has been added over the
      last 50 years, it is not yet possible to provide a detailed, quantitative
      understanding of these important excretory systems.

PMID- 8743471
TI  - Scales of urine acidification: apical membrane-associated particles in turtle
      bladder.
AB  - Since the time of Smith, studies of urinary acidification have shifted their
      focus to ever smaller scales and have revealed iterative patterns or
      organization. For this review we focus on the organization of intra- and
      submembrane particles at the scale of the apical cell membrane of the H+
      secreting, alpha intercalated cells. Particles were examined quantitatively by
      thin section and freeze-fracture (FF) electron microscopy. Ongoing studies in
      turtle bladder indicate that the density of submembrane particles (studs) per
      micron 2 is approximately the same as that of spherical units (SPUs) forming
      linear (rod-shaped) arrays on FF. This one-to-one relationship is observed in the
      presence or absence of CO2 and suggests that CO2-induced changes in H+ secretion
      do not involve dissociation of the intramembrane (channel) and cytoplasmic
      (catalytic) parts of the H-ATPase. Structure-function studies based on density
      estimates of the particles, morphometry of the H+ secreting cell population, and
      measurement of H+ transport rate prior to fixation permit functional correlation
      across scales of study.

PMID- 8743472
TI  - Distal urinary acidification from Homer Smith to the present.
AB  - Since Smith's time, the essential role of collecting duct intercalated cells in
      controlling net acid excretion has been recognized. Rather than employing an H(+)
      exchange mechanism, intercalated cells have V-ATPase on the plasma membrane and
      in plasmalemma-associated tubulovesicles, which functions in the bicarbonate
      reabsorption, regeneration, and bicarbonate secretion required for acid-base
      homeostasis. Several distinct mechanisms participate in regulating V-ATPase
      driven H+ secretion in different cell types: (1) Renal epithelial cells have the
      capacity to express different structural forms of V-ATPase that have intrinsic
      differences in their enzymatic properties. 2) The kidney produces cytosolic
      regulatory proteins, capable of interacting directly with the V-ATPase, that may
      modify its activity. V-ATPases in different cell types may differ in the degree
      to which their activity is affected by regulatory factors, as a result of
      variations in V-ATPase structure. (3) In the alpha intercalated cell, the number
      of active V-ATPases on the luminal membrane is controlled in vivo by membrane
      vesicle-mediated traffic that may require unidentified mediators. In the beta
      intercalated cell, the number of active V-ATPases on the basolateral membrane may
      be controlled by regulated assembly and disassembly, responding directly to
      extracellular pH.

PMID- 8743473
TI  - Role of ion exchangers in mediating NaCl transport in the proximal tubule.
AB  - The reabsorption of NaCl in the proximal tubule occurs passively through the
      paracellular pathway, and actively by a transcellular route. Transcellular NaCl
      transport involves Na(+)-coupled Cl- entry across the apical membrane by two
      mechanisms involving Cl(-)-organic anion exchange. One mechanism is Cl(-)-formate
      exchange with recycling of formate from lumen to cell by H(+)-coupled formate
      transport in parallel with Na(+)-H+ exchange. A second mechanism is Cl(-)-oxalate
      exchange with recycling of oxalate from lumen to cell by oxalate-sulfate exchange
      in parallel with Na(+)-sulfate cotransport. Cl- exit across the basolateral
      membrane is most likely mediated by Cl- channels. Apical membrane Na(+)-H+
      exchange is involved in mediating both NaHCO3 and NaCl reabsorption in the
      proximal tubule. Immunocytochemical studies indicate that NHE3 is the principal
      Na(+)-H+ exchanger isoform expressed on the brush border membrane. Detection of
      NHE3 in a subapical, intracellular, vesicular compartment in proximal tubule
      cells is consistent with its possible regulation by membrane trafficking. That
      NHE3 is the isoform responsible for apical membrane Na(+)-H+ exchange activity is
      supported by studies of inhibitor sensitivity, and by studies demonstrating
      increased expression of NHE3 protein in association with enhanced Na(+)-H+
      exchange activity during renal maturation and in response to glucocorticoids and
      metabolic acidosis.

PMID- 8743474
TI  - On the mechanism of bicarbonate exit from renal proximal tubular cells.
AB  - We compare here the results of electrophysiological measurements on proximal
      tubular cells performed on rat kidney in vivo and on isolated rabbit and rat
      tubules in vitro. Based on different effects of carbonic anhydrase inhibitors in
      the in vivo and in vitro preparation, we conclude that NaHCO3 cotransport across
      the basolateral cell membrane functions as Na(+)-CO3(2-)-HCO3- cotransport in
      vivo, but as Na(+)-HCO3(-)-HCO3- cotransport in the classical in vitro
      preparation. The former, but not the latter, transport mode is characterized by
      generation of local disequilibrium pH/CO3(2-) concentrations that oppose fluxes
      if membrane-bound carbonic anhydrase is inhibited. In support of this conclusion,
      we find that overall transport functions with a HCO3- to Na+ stoichiometry of 3:1
      in vivo (since each transported CO3(2-) eventually generates 2 HCO3- ions), but
      2:1 in vitro. This has been deduced from various measurements, among them super
      Nernstian and reverse nernstian, potential responses to changing ion
      concentrations which are characteristic of obligatorily coupled cation-anion
      cotransporters, but are not known in classical electrochemistry. The different
      transport modes in vivo and in vitro suggest that isolated proximal tubules have
      functional deficits compared to proximal tubules in vivo.

PMID- 8743475
TI  - Transcriptional responses to tubule challenges.
AB  - Adaptation to physiological stimuli often involves changes in gene transcription.
      Studies of hyperosmolar stress in renal epithelial cells have provided an ideal
      paradigm for understanding regulation of gene expression. Renal epithelial cells
      respond very differently to hyperosmolar NaCl and urea and several strategies
      including cloning based on known biological function, candidate gene analysis,
      and differential display analysis have successfully identified many genes induced
      by these hyperosmolar challenges. Hyperosmolar NaCl produces adverse effects on
      cellular biosynthetic processes and compensatory increases are observed in
      transcription of transporters, stress proteins, and metabolic enzymes. In
      contrast, hyperosmolar urea fails to inhibit biosynthetic processes but,
      nonetheless, initiates a very specific program of gene expression in renal
      epithelial cells. This program appears to involve a urea sensor/receptor system
      which activates transcription and translation of the zinc-finger transcription
      factor Egr-1. This work highlights the concept that rapid analysis of
      differential gene expression will enable one to define cellular programs of gene
      expression involving up- and down-regulation of functionally-related gene
      families.

PMID- 8743476
TI  - Regulation of the myo-inositol and betaine cotransporters by tonicity.
AB  - Cells of the hypertonic renal medulla accumulate high concentrations of the non
      perturbing osmolytes myo-inositol, betaine, and taurine, and are thereby
      protected from the perturbing effects of hypertonicity. Kidney-derived MDCK cells
      accumulate high levels of these three non-perturbing osmolytes when cultured in
      hypertonic medium and have been used to study their accumulation. The increase in
      the intracellular concentration of these non-perturbing osmolytes is the result
      of an increase in the abundance of the mRNA for the specific cotransporter for
      each osmolyte and the ensuing increase in the activity of the three specific
      sodium coupled transporters. The increased abundance of mRNA for the myo-inositol
      and the betaine cotransporters is driven by an increase in the rate of
      transcription of their genes. We have identified a 13 basepair cis-acting element
      in the 5' flanking region of the gene for the betaine cotransporter. The element
      is an enhancer that mediates the transcriptional response to hypertonicity. The
      protein(s) that binds to the tonicity responsive element is much more active in
      hypertonic than in isotonic cells, and is in all likelihood the mediator of the
      transcriptional response to changes in tonicity.

PMID- 8743477
TI  - Coordinate regulation of organic osmolytes in renal cells.
AB  - Adaptation of cells to prolonged hypertonicity generally involves accumulation of
      compatible organic osmolytes. Renal medullary cells in vivo and in tissue culture
      accumulate several different organic osmolytes, including sorbitol, inositol,
      betaine, and glycerophosphocholine (GPC) in response to hypertonicity. For the
      total concentration of these organic osmolytes to be appropriate for the ambient
      tonicity, an increase in one should cause the others to fall, minimizing changes
      in their total concentration. The experiments presented here demonstrate this in
      tissue culture and investigate the mechanisms involved. Sorbitol is synthesized
      from glucose, catalyzed by aldose reductase. Betaine is transported into the
      cells. Hypertonicity increases transcription of the aldose reductase and betaine
      transporter genes, ultimately elevating cell sorbitol and betaine. If aldose
      reductase is inhibited, which prevents accumulation of sorbitol, betaine
      transporter gene expression increases, resulting in a higher cell betaine that
      compensates for the lower sorbitol. Conversely, when cell betaine is altered by
      changing its concentration in the medium, aldose reductase transcription changes
      reciprocally, resulting in compensating changes in cell sorbitol. Hypertonicity
      increases GPC by inhibiting GPC:choline phosphodiesterase (GPC:PDE), an enzyme
      that degrades GPC. When cell betaine or inositol is increased by raising its
      concentration in the medium, GPC:PDE activity rises, reducing cell GPC. Thus, the
      total of the osmolytes, rather than the level of any individual one, is
      maintained.

PMID- 8743478
TI  - Osmoregulation in the renal papilla: membranes, messengers and molecules.
AB  - This contribution summarizes recent progress in the understanding of the
      molecular basis of the release of organic osmolytes that occurs when inner
      medullary cells are confronted with a drop in osmolarity in their environment.
      For sorbitol release across the basolateral membrane an increase in intracellular
      calcium seems to be the prominent signal, initiated by G-protein activation,
      followed by phosphatidylcholine phospholipase activation and generation of
      arachidonic acid. The increase in betaine permeability is also G-protein
      dependent but calcium independent, and is restricted to the basal-lateral cell
      face. Myo-inositol and glycerophosphorylcholine efflux are calcium and G-protein
      independent and occur both across the apical and basolateral membrane, although
      to a different extent. Taurine release is also calcium and G-protein independent;
      a swelling-activated anion channel at the basolateral membrane represents the
      major efflux pathway.

PMID- 8743479
TI  - Organic osmolyte channels: transport characteristics and regulation.
AB  - Erythrocytes of the skate (Raja erinacea) exposed to hypotonic stress swell and
      then undergo a volume regulatory decrease by releasing taurine and other
      osmolytes. Previous studies showed that taurine release occurs via a volume
      activated, Na(+)-independent, bi-directional transporter that has the properties
      of a size-limited channel. We now report on the transport characteristics of this
      channel and its regulation. Kinetic, competition and inhibitor studies indicate
      that polyols (myo-inositol) and trimethylamines (betaine) are transported by the
      same channel as taurine. Although the identity of the channel is still unknown a
      variety of evidence suggests that band 3 is involved in either channel formation
      or regulation. Hypotonicity causes phosphorylation and structural changes in band
      3. Under isotonic conditions band 3 is predominantly in the dimeric form.
      Hypotonicity causes a shift to tetrameric band 3. We hypothesize that the band 3
      tetramer either forms or regulates an osmolyte channel. The finding that
      expression of band 3 protein increases osmolyte channel activity in Xenopus
      oocytes supports this hypothesis.

PMID- 8743480
TI  - Single channel properties of a volume sensitive anion channel: lessons from noise
      analysis.
AB  - Swelling activated anion channels have recently been recognized to play an
      important role in not only volume regulatory electrolyte movement, but also in
      organic osmolyte transport. A swelling-activated, outwardly rectifying anion
      channel termed VSOAC (volume-sensitive organic osmolyte/anion channel) is a major
      pathway for swelling-induced loss of organic osmolytes and organic anions from
      mammalian cells. VSOAC has been described in numerous cell types. Until recently,
      however, the unitary conductance and gating kinetics of VSOAC were uncertain.
      Stationary noise analysis and single channel measurements have produced estimates
      for the unitary conductance of swelling-activated, outwardly rectifying anion
      channels that vary by > 15-fold. This review describes our current understanding
      of the single channel properties of VSOAC.

PMID- 8743481
TI  - Cellular and molecular events in the action of antidiuretic hormone.
AB  - The urinary concentrating mechanism and the action of antidiuretic hormone (ADH)
      were subjects of great controversy in the 1950's. Since then, steady progress has
      been made in our understanding of the cellular action of ADH. We have a good
      picture of the cyclic process by which vesicles carrying water channels move from
      cytoplasm to apical membrane, deposit water channels, and are then recovered by
      endocyosis. There is progress towards a complete description of the structure of
      the channels themselves. As well, in secretory cells such as the nerve terminal
      and the chromaffin cell, there are principles of cytoskeletal control and vesicle
      docking that appear to apply to the nephron.

PMID- 8743482
TI  - Vasopressin receptors in health and disease.
AB  - The molecular cloning and characterization of receptors for the nonapeptide
      hormone family vasopressin-oxytocin was rapidly followed by the identification of
      mutations in the V2 receptor gene segregating with the clinical phenotype in more
      than a hundred families with X-linked nephrogenic diabetes insipidus. Together
      with the recent cloning of the vasopressin-regulated water channel in the apical
      membrane of the collecting duct tubule and of the identification of rare
      autosomal recessive nephrogenic diabetes insipidus patients with mutations in the
      AQP2 gene, these developments enable carrier detection and early diagnosis of
      infants with congenital nephrogenic diabetes insipidus.

PMID- 8743483
TI  - Renal aquaporins.
AB  - Aquaporins (AQPs) are a newly recognized family of transmembrane proteins that
      function as molecular water channels. At least four aquaporins are expressed in
      the kidney where they mediate rapid water transport across water-permeable
      epithelia and play critical roles in urinary concentrating and diluting
      processes. AQP1 is constitutively expressed at extremely high levels in the
      proximal tubule and descending limb of Henle's loop. AQP2, -3 and -4 are
      expressed predominantly in the collecting duct system. AQP2 is the predominant
      water channel in the apical plasma membrane and AQP3 and -4 are found in the
      basolateral plasma membrane. Short-term regulation of collecting duct water
      permeability by vasopressin is largely a consequence of regulated trafficking of
      AQP2-containing vesicles to and from the apical plasma membrane.

PMID- 8743484
TI  - The aquaporin family of water channels in kidney: an update on physiology and
      pathophysiology of aquaporin-2.
AB  - The long-standing problem of membrane water transport has been advanced by the
      recognition of a new family of water transport proteins, the "aquaporins" [1-3].
      Not surprisingly, water transport is a major process in kidney physiology, and
      the biology of aquaporins is most thoroughly understood in that organ. We
      reviewed in detail the status of aquaporins in the kidney only one year ago [4],
      but the subsequent progress has dictated the need for an update. This seems
      especially appropriate in honor of the 100th birthday of Homer Smith, the pioneer
      whose foresight initiated this field.

PMID- 8743485
TI  - Whys and wherefores of juxtaglomerular apparatus function.
AB  - The juxtaglomerular apparatus is an anatomic structure which links the distal end
      of the thick ascending limb at the macula densa with the glomerular vascular
      pole. Specialized interstital cells and renin containing granular cells are
      located in the vascular hilum at this site. Evidence has accumulated that this
      connection is critical for local regulation of renin secretion and glomerular
      vascular tone via the tubuloglomerular feedback mechanism. The tubuloglomerular
      feedback mechanism maintains a constant chloride concentration at the macula
      densa at a set point determined by the volume state of the animal, a effect
      probably important for adjustment of renin secretion to changing salt balance.
      Evidence supporting these two regulatory roles is reviewed here.

PMID- 8743486
TI  - Importance of nitric oxide in the control of renal hemodynamics.
AB  - The kidney vasculature is under tonic control by nitric oxide (NO) and in cortex,
      NO controls RA and Kf. Systemic NO inhibition leads to systemic hypertension,
      increases in RE, mediated by Ang II and ET, and direct effects on RA and Kf. The
      relationship between NO and other vasoconstrictor systems is variable. In the
      conscious relaxed animal, vasoconstrictor activity is low, yet acute NO
      inhibition leads to pressor and renal vasoconstrictor responses. At physiologic
      levels, ET unexpectedly is a renal vasodilator, possibly via NO generation at RA.
      When vasoconstrictor activity is high, NO is very important in maintenance of
      renal perfusion. Chronic L-NAME produces dose dependent systemic and glomerular
      capillary hypertension and eventual proteinuria and glomerular damage. NO
      deficiency is key in this process, although the hypertension becomes refractory
      to L-arginine administration and dependent on Ang II and the SNS, by mechanisms
      not yet defined. In contrast, the renal vasculature remains fully responsive to L
      arginine, suggesting that pressor and renal vascular responses to chronic NO
      inhibition are separately regulated. NO generated from iNOS does not normally
      control BP or renal hemodynamics. The relative contributions of NO from bNOS and
      eNOS, and importance of NOS in different locations in the kidney, remain to be
      determined.

PMID- 8743487
TI  - Role of atrial natriuretic factor in volume control.
AB  - Atrial natriuretic factor (ANF) is a 28 amino acid polypeptide hormone secreted
      mainly by the heart atria in response to atrial stretch. ANF acts on the kidney
      to increase sodium excretion and GFR, to antagonize renal vasoconstriction, and
      to inhibit renin secretion. In the cardiovascular system, ANF antagonizes
      vasoconstriction, and shifts fluid from the intravascular to the interstitial
      compartment. In the adrenal gland, ANF is a powerful inhibitor of aldosterone
      synthesis. ANF participates importantly in the natriuretic response to acute and
      chronic volume overload. ANF's property of shifting fluid from the vascular to
      the interstitial compartment acts as a buffering device, guarding against
      excessive plasma volume expansion in face of an increased total extracellular
      fluid volume. ANF is also a physiological modulator of GFR, and mediates nephron
      hyperfiltration and natriuresis when salt excretion is threatened by a reduction
      in the number of nephrons. Guanylyl cyclase (GCA) receptors mediate the effects
      of ANF by generating cGMP. Clearance receptors remove ANF from the circulation by
      receptor-mediated endocytosis, and serve as a hormone buffer system to impede
      large inappropriate fluctuations in plasma levels of ANF. The specific structure
      function-dynamics relationships of these receptors serve to modulate the role of
      ANF in pressure-volume homeostasis.

PMID- 8743488
TI  - Aldosterone and potassium homeostasis.
AB  - The presently accepted regulators of the homeostatic excretion of potassium are
      the plasma concentrations of aldosterone and potassium. Evidence for a role of
      aldosterone is reviewed, and it is pointed out that aldosterone is kaliuretic at
      supraphysiologic levels but has little kaliuretic activity within its normal
      secretory range. Elevation of plasma potassium above its normal range enhances
      the kaliuretic action of aldosterone. Elevation of plasma potassium above, but
      not within, its normal range is strongly kaliuretic. In sheep the kaliuresis
      induced by intake of a potassium rich meal cannot be explained by changes in
      aldosterone or plasma potassium. A kaliuretic reflex arising from receptors in
      the gut, portal vein or liver has been proposed the explain the meal-induced
      kaliuresis. This putative reflex involves the central nervous system and efferent
      kaliuretic factors other than aldosterone and plasma potassium. Evidence for the
      involvement of the central nervous system and undetermined kaliuretic regulatory
      factors can be found in studies of the physiologic circadian rhythm of renal
      potassium excretion. This rhythmic excretion does not appear to depend on changes
      in either aldosterone or plasma potassium.

PMID- 8743489
TI  - Cellular mechanisms for bi-directional regulation of tubular sodium reabsorption.
AB  - The molecular mechanisms underlying the regulation of sodium excretion are
      incompletely known. Here we propose a general model for a bi-directional control
      of tubular sodium transporters by natriuretic and antinatriuretic factors. The
      model is based on experimental data from studies on the regulation of the
      activity of Na+,K+-ATPase, the enzyme that provides the electrochemical gradient
      necessary for tubular reabsorption of electrolytes and solutes in all tubular
      segments. Regulation is carried out to a large extent by autocrine and paracrine
      factors. Of particular interest are the two catecholamines, dopamine and
      norepinephrine. Dopamine is produced in proximal tubular cells and inhibits
      Na+,K+-ATPase activity in several tubule segments. Renal dopamine availability is
      regulated by the degrading enzyme, catechol-O-methyl transferase. Renal
      sympathetic nerve endings contain norepinephrine and neuropeptide Y (NPY).
      Activation of alpha-adrenergic receptors increase and activation of beta
      adrenergic receptors decrease Na+,K+-ATPase activity. alpha-Adrenergic
      stimulation increases the Na+ affinity of the enzyme and thereby the driving
      force for transcellular Na+ transport. NPY acts as a master hormone by
      synergizing the alpha- and antagonizing the beta-adrenergic effects. Dopamine and
      norepinephrine control Na+,K+-ATPase activity by exerting opposing forces on a
      common intracellular signaling system of second messengers, protein kinases and
      protein phosphatases, ultimately determining the phosphorylation state of Na+,K+
      ATPase and thereby its activity. Important crossroads in this network are
      localized and functionally defined. Phosphorylation sites for protein kinase A
      and C have been identified and their functional significance has been verified.

PMID- 8743490
TI  - Endogenous ouabain: role in the pathogenesis of hypertension.
AB  - Substantial evidence implicates impaired renal excretion of sodium as the major
      culprit in the pathogenesis of hypertension. The key question is: How does the
      impairment of Na+ excretion lead to increased peripheral vascular resistance and
      elevation of the blood pressure? Here we describe the evidence that elevated
      levels of a recently-discovered adrenal cortical hormone, endogenous ouabain,
      plays a central role in this process. This hormone inhibits the Na+ pump and
      raises intracellular Na+. Then, as a result of Na/Ca exchange, cytosolic Ca2+
      and, more importantly, intracellular stores of Ca2+, are increased in vascular
      smooth muscle (VSM), vasomotor neurons, and endothelial cells, as well as in many
      other types of cells. Consequently, these cells become hyper-responsive because
      the cytosolic Ca2+ transients induced by cell activation are enhanced. The
      synergy of augmented sympathetic neuron transmitter release and augmented VSM
      cell responsiveness may account for the increased arterial tone and peripheral
      vascular resistance that is the hallmark of hypertension.

PMID- 8743491
TI  - Renal mechanisms of genetic hypertension: from the molecular level to the intact
      organism.
AB  - Human primary hypertension is a polygenic disease; its phenotypic expression is
      modulated by the environment. Though the kidney can play a major role in the
      initiation and maintainance of hypertension, many questions remain open. Kidney
      cross-transplantation demonstrated that hypertension can be transplanted with the
      kidney in all strains of genetically hypertensive rats where such experiments
      have been carried out. Data consistent with those in rats were also obtained in
      humans. Many abnormalities in kidney function and ion transport were described in
      hypertensive rats and humans, but the logical sequence from genetic-molecular to
      cellular abnormality that causes hypertension via modification of kidney function
      is difficult to prove. We established this sequence in Milan hypertensive rats
      using a variety of experimental techniques (isolated kidney and renal cell
      function, cell membrane ion transport, cross-immunization with membrane proteins,
      molecular biology, genetic crosses and manipulation). Such studies led to the
      identification of a polymorphism in the cytoskeletal protein adducin. This
      polymorphism seems involved in blood pressure regulation both in rats and humans.
      Preliminary results suggest that adducin polymorphism affects kidney function by
      modulating the overall capacity of tubular epithelial cells to transport ions
      modifying the assembly of actin cytoskeleton.

PMID- 8743492
TI  - How is plasma calcium held constant? Milieu interieur of calcium.
AB  - Extracellular or plasma calcium ion concentration is held constant at 5 mg/dl
      through the actions of parathyroid hormone (PTH), vitamin D, and calcitonin, on
      their target organs, kidney and bone. The thresholds of renal tubular calcium
      reabsorption and bone resorption and formation are both set at 5 mg/dl. The set
      point of PTH secretion is also set at 5 mg/dl plasma calcium ion. Therefore, the
      sensing system (parathyroid cell) and the effectors, kidney and bone, are all set
      to maintain plasma calcium at 5 mg/dl, perhaps through membrane-bound calcium
      sensor proteins. The effectiveness of this system depends upon the presence of
      bone remodeling, which allows a swift shift of plasma calcium from and to bone in
      response to PTH and calcitonin, respectively. In this regard, directing
      hematopoiesis to bone marrow that provides bone resorbing osteoclasts is
      critical. It is likely that this shift of hematopoiesis occurs through evolution
      at the transition from the aquatic to the terrestrial life, and this event is
      directed by expression of "homing molecule" in bone marrow stromal cells. This
      brief review provides a factual and conceptual framework of the current
      understanding of the milieu interieur of the calcium ion.

PMID- 8743493
TI  - Endocrine disturbances of calcium metabolism in uremia: renal causes and systemic
      consequences.
AB  - The genesis of the hormonal disturbances in calcium metabolism of renal failure
      is complex, but can be understood basically as the consequence of the deranged
      endocrine function of the kidney, that is, failing biosynthesis of the renal
      secosterol hormone 1,25 OH2D3. It is of interest to note how our concepts
      concerning the genesis of these disturbances, and the role of 1,25 OH2D3 therein,
      have changed with time. We illustrate this using three examples: (i) the signals
      activating the parathyroid gland in early renal failure; (ii) the genesis of
      parathyroid hyperplasia; and (iii) the actions of 1,25 OH2D3 in renal failure
      unrelated to calcium control.

PMID- 8743495
TI  - The hyperfiltration theory: a paradigm shift in nephrology.
AB  - Experimental studies incriminate glomerular hypertension in mediating progressive
      renal damage after any of a variety of initiating injuries. Prevention of
      glomerular hypertension by dietary protein restriction or antihypertensive
      therapy lessens progressive glomerular damage in several experimental models of
      chronic renal disease. Glomerular hypertension and hyperfiltration also occur in
      humans with diabetes mellitus, solitary or remnant kidneys, and various forms of
      acquired renal disease. Clinical studies indicate that dietary protein
      restriction and antihypertensive therapy also slow progression in many of these
      disorders. Large multicenter trials confirm the beneficial effects of these
      therapeutic maneuvers on the rate of progression of chronic renal disease.

PMID- 8743494
TI  - Renal brush border membrane Na/Pi-cotransport: molecular aspects in PTH-dependent
      and dietary regulation.
AB  - Inorganic phosphate (Pi) is reabsorbed in renal proximal tubules in a sodium (Na)
      dependent manner involving brush border Na/Pi-cotransporter(s). Regulation of
      renal Pi-reabsorption, such as by parathyroid hormone (PTH) and/or by dietary Pi
      deprivation, involves alterations in the rate of Na/Pi-cotransport. Two
      structurally different Na/Pi-cotransporters have been identified: type I
      transporter and type II-transporter. The related mRNAs and proteins are located
      in the proximal tubule and in the brush border membrane. In heterologous
      expression systems type I and type II Na/Pi-cotransporters mediate Na/Pi
      cotransport. Characterization of the transport properties suggested that the type
      II transporter is "responsible' for brush border membrane Na/Pi-cotransport (as
      observed in isolated vesicles). Administration of PTH to rats resulted in an
      inhibition of brush border membrane Na/Pi-cotransport (vesicles) and in a reduced
      brush border membrane content of the type II transporter. Feeding low Pi-diets
      resulted in an up-regulation of Na/Pi-cotransport (vesicles) and of type II
      transporter content; only after a prolonged exposure to low Pi-diets (more than 4
      hr) was an increase in specific mRNA content observed. Refeeding high Pi diets
      had the opposite effects on Na/Pi-cotransport activity and on type II transporter
      protein. It is currently the task of future experiments to define the specific
      mechanisms leading to protein-synthesis-independent (PTH, acute Pi-deprivation,
      Pi-refeeding) and to protein-synthesis-dependent (prolonged Pi-deprivation)
      regulation of the type II Na/Pi-cotransporter.

PMID- 8743496
TI  - Benefits of long-term antihypertensive treatment on prognosis in diabetic
      nephropathy.
AB  - We assessed the prognosis of diabetic nephropathy during long-term
      antihypertensive treatment as compared to the prognosis during the natural
      history of this complication in a prospective study of all IDDM patients (N = 45)
      aged under 50 with onset of diabetes before the age of 31 who developed diabetic
      nephropathy between 1974 and 1978 at Steno Diabetes Center, and were followed
      until death or for at least 16 years [median 16 (4 to 21) years].
      Antihypertensive treatment was started 3 (0 to 13) years after onset of diabetic
      nephropathy. Mean arterial blood pressure at start of antihypertensive treatment
      was 148/96 (sd 12/10) mm Hg and 143/86 (16/6) mm Hg during the whole interval of
      antihypertensive treatment (P < 0.01). The cumulative death rate was 45% (95%
      C.I. 38 to 52) 16 years after onset of diabetic nephropathy, in contrast to
      previous reports 88% and 94% 12 and 16 years after onset of diabetic nephropathy,
      respectively. The median survival time in our study exceeded 16 years as compared
      to five and seven years in untreated patients in the past. Uremia was the main
      cause of death (12 patients; 55%). In 1994 serum creatinine was 116 (74 to 311)
      mumol/liter in the 23 surviving patients. The preservation of kidney function and
      the prognosis of diabetic nephropathy has improved during the past two decades
      mainly because of effective antihypertensive treatment.

PMID- 8743497
TI  - Role of dietary protein and blood pressure in the progression of renal disease.
AB  - The Modification of Diet in Renal Disease (MDRD) Study examined the effect of two
      interventions, reduction of dietary protein and control of blood pressure below
      the usual recommended level, on the progression of chronic renal disease.
      Patients in Study A (N = 585), GFR of 25 to 55 ml/min, were randomized to a group
      following a usual or low protein diet (1.3 or 0.58 g/kg body wt/day) and
      maintained at a usual (107 mm Hg) or low (92 mm Hg) mean arterial pressure.
      Patients in Study B (N = 255), GFR 13 to 24 ml/min, were randomized to a group
      following a low protein diet or a very low protein diet (0.28 g/kg body wt/day
      supplemented with a mixture of keto acids and amino acids), and maintained at a
      usual or low blood pressure level. During the first four months of follow-up in
      Study A, GFR declined at a faster rate in patients assigned a low protein diet or
      low blood pressure goal. The "terminal" GFR slope (measured from the fourth month
      of follow-up and projected to 3 years of follow-up) was 28% less, as a mean, in
      patients in the low protein group versus those on the usual protein diet (P =
      0.009). Also, the low blood pressure group showed a significantly (P = 0.006)
      slower progression of renal disease (29%) than the usual blood pressure group.
      The effects of low blood pressure on the GFR decline were significantly related
      to the level of proteinuria during the baseline period. The results of Study B
      strongly suggest beneficial effects of the very low protein diet on renal
      function in patients with a GFR less than 25 ml/min.

PMID- 8743498
TI  - Renal effects of angiotensin II receptor blockade in normotensive subjects.
AB  - Several new non-peptide, orally active, angiotensin II receptor antagonists have
      recently been developed which enable to block the renin-angiotensin system at the
      AT1 receptor site. In contrast to angiotensin converting enzyme (ACE) inhibitors,
      these antagonists do not interfere with the metabolism of kinins. The effect of
      these agents on renal function may thus potentially differ from those of ACE
      inhibitors. Therefore, the renal pharmacology of various angiotensin II receptor
      antagonists has been examined in normotensive subjects. In normotensive subjects,
      losartan and irbesartan have been shown to have no effect on glomerular
      filtration rate and to induce either no change or a modest increase in renal
      blood flow. These results were confirmed thereafter in hypertensive patients
      where losartan produced a renal vasodilation with no change in glomerular
      filtration. In healthy subjects, both losartan and irbesartan induce an acute
      increase in urinary sodium excretion. The natriuretic response to losartan is
      proportionally more important during salt-depletion. In contrast to other
      angiotensin II receptor antagonists, losartan has a unique property to increase
      uric acid excretion. In this paper we show that this property is due to the
      potent inhibitory effect of the parent compound of losartan on the urate/anion
      transport in the human renal proximal tubule.

PMID- 8743499
TI  - Progress in human gene therapy.
AB  - There have been major advances in our understanding of the molecular biology and
      pathophysiology of human disease over the past decade. This expanding knowledge
      of the basic mechanisms of human disease coupled with the development of
      efficient methods of transferring genes to mammalian cells has stimulated
      considerable interest in treating diseases with gene therapy. Clinical trials
      have demonstrated that human gene transfer is possible, that several strategies
      exist for successfully introducing exogenous genes to human cells, that a variety
      of transgenes can evoke biologic responses important to human diseases, and that
      gene transfer can provide valuable insights into the pathophysiology of human
      disorders. Initial clinical trials have yielded encouraging results and adverse
      reactions have been uncommon. Despite the advances in human gene transfer,
      significant obstacles need to be overcome before it becomes a firmly established
      therapeutic option for human illness. The potential benefits of utilizing human
      gene therapy in the treatment of hereditary and acquired disease have generated
      interest in further advancing this remarkable technology.

PMID- 8743500
TI  - Protein glycation in the kidney: role in diabetes and aging.

PMID- 8743501
TI  - Physiology and pathophysiology of nitric oxide.
AB  - Nitric oxide (NO) was discovered to be a potent vasodilator, inhibitor of
      platelet aggregation, and active species of nitroglycerin before the discovery of
      endothelium-derived relaxing factor (EDRF) in 1980. Subsequent studies revealed
      that EDRF is NO, and is synthesized by mammalian cells from L-arginine through a
      complex oxidation reaction catalyzed by the flavo-hemoprotein NO synthase (NOS).
      NOS catalyzes the NADPH- and oxygen-dependent oxygenation of L-arginine to NO
      plus L-citrulline in a reaction that requires at least six cofactors including
      NADPH, FAD, FMN, tetrahydrobiopterin, heme, and calmodulin. NO elicits its known
      physiological actions by activating cytosolic guanylate cyclase, which converts
      GTP to cyclic GMP. Endothelial NOS and neuronal NOS are constitutively present
      and activated by increases in intracellular calcium triggered by endogenous
      chemicals. NO then diffuses into nearby target cells to elevate cyclic GMP levels
      and thereby trigger cell function. NOS activity can also be regulated by a
      negative feedback mechanism involving NO itself. Much greater quantities of NO
      are produced pathophysiologically by a distinct form of NOS that can be induced
      in vascular endothelium, smooth muscle and macrophages by endotoxin and
      cytokines. This high-output production of NO is not regulated by calcium and is
      cytotoxic by mechanisms involving interaction with iron-containing proteins.

PMID- 8743502
TI  - Nitric oxide in the juxtaglomerular apparatus.

PMID- 8743503
TI  - TGF and nitric oxide: effects of salt intake and salt-sensitive hypertension.
AB  - The tubuloglomerular feedback response (TGF) entails vasoconstriction of the
      afferent arteriole (AA) and a fall in the glomerular capillary pressure (PGC) and
      single nephron glomerular filtration rate (SNGFR) during NaCl reabsorption in the
      macula densa (MD) segment. Recent studies have concluded that nitric oxide (NO)
      is synthesized by the MD and blunts the TGF response. Since a high salt (HS) diet
      has been found to blunt TGF, we tested the effects of salt intake on the response
      to blockade of nitric oxide synthesis. For the first series, the TGF was assessed
      from changes in proximal stop-flow pressure (PSF, an index of PGC in response to
      graded perfusion of the loop of Henle (LH) with name tubular fluid (NTF). Loop
      perfusion with 10(-3) M L-NMA did not affect the PSF responses of low salt (LS)
      rats, but reduced (P < 0.01) the PSF of HS rats during perfusion at 20 nl.min-1 (
      1.5 +/- 0.4 mm Hg; P < 0.01) and at 40 nl.ml-1 (-2.2 +/- 0.5 mm Hg; P < 0.001).
      For the second series, the TGF responses of salt sensitive Dahl/Rapp (ssDR) rats
      were compared to Sprague-Dawley (SD) rats. Both groups were studied 8 to 10 days
      after starting HS or LS diets by loop perfusion of artificial tubular fluid at 40
      nl.min-1. Compared to Sprague-Dawley rats, the ssDR had blunted maximal TGF
      responses during LS (SD, 8.2 +/- 0.3 vs. ssDR, 6.4 +/- 0.3 mm Hg; P < 0.001), but
      not during HS. During LS intake, addition of L-NMA to ATF perfusing the loop of
      Henle did not alter the maximal TGF response of either strain. However, during HS
      intake L-NMA increased the maximal TGF response of SD rats (4.4 +/- 0.4 to 6.7 +/
      0.5 mm Hg; P < 0.001) but did not significantly change the PSF of ssDR rats (5.2
      +/- 0.3 to 5.7 +/- 0.5 mm Hg; NS). We conclude that the TGF response is enhanced
      by blockade of NOS during HS, but not LS intakes; this response to NOS blockade
      during HS intake is lost in salt sensitive Dahl/Rapp rats.

PMID- 8743504
TI  - Differential inducibility of angiotensin II AT2 receptor between SHR and WKY
      vascular smooth muscle cells.
AB  - Although the fetal aorta expresses a substantial amount of angiotensin II type 2
      receptors, the expression level of angiotensin II type 2 receptors in the adult
      aorta and cultured vascular smooth muscle cells is very low or even absent.
      Prolonged serum depletion (6 to 8 days) with a supplement of insulin, transferrin
      and sodium selenite induced angiotensin II type 2 receptors and mRNA in cultured
      vascular smooth muscle cells from Wistar Kyoto rats. Insulin was found to be
      essential for the induction of the receptor. However, these receptors could not
      be induced in cultured vascular smooth muscle cells from spontaneously
      hypertensive rats. These results suggest that: (1) insulin plays an important
      role for the expression of the angiotensin II type 2 receptor gene; and (2) the
      type 2 receptor gene expression is differentially regulated between cultured
      vascular smooth muscle cells of Wistar Kyoto rats and spontaneously hypertensive
      rats.

PMID- 8743505
TI  - Angiotensin I converting enzyme and chymase in cardiovascular tissues.
AB  - Recent studies have provided evidence that the human cardiovascular tissues
      contain components of the renin-angiotensin system: angiotensinogen, renin,
      angiotensin I converting enzyme (ACE), chymase and angiotensin II (Ang II)
      receptors. In addition to ACE, a cardiac Ang II forming serine proteinase, human
      heart chymase, has been identified in the human left ventricle. Unlike rat heart,
      only a minor (approximately 11%) component of Ang II forming activity in the
      human left ventricle was due to ACE, since the majority (approximately 80%) of
      activity was due to chymase. Human heart chymase has been purified to homogeneity
      and characterized. Recently, the cDNA and gene for this enzyme have been cloned.
      Biochemical characterization revealed that heart chymase is the most efficient
      and specific Ang II forming enzyme described thus far. The different cellular and
      regional distribution of ACE and heart chymase in the heart as well as in blood
      vessels implies distinct pathophysiological roles for these two Ang II forming
      enzymes. Several reports indicate that ACE-independent Ang II formation appears
      to take place in hypoxic or ischemic heart or blood vessel in vivo and to be
      involved in vascular remodeling after balloon injury. Therefore, it is very
      important to clarify the detailed mechanisms of the tissue Ang II formation in
      humans and its contribution to the pathophysiological changes in cardiovascular
      disease. In this review, we review the pathophysiological roles of the two main
      Ang II forming enzymes, ACE and chymase, in cardiovascular homeostasis.

PMID- 8743506
TI  - Pharmacokinetic-pharmacodynamic relationships of three angiotensin II receptor
      antagonists in normal volunteers.

PMID- 8743507
TI  - Congenital oligonephropathy: The fetal flaw in essential hypertension?
AB  - In 1988, Brenner, Garcia and Anderson advanced the hypothesis that the nephron
      endowment at birth is inversely related to the risk of developing essential
      hypertension in later life. This novel perspective on the origins of essential
      hypertension was taken from the viewpoint that the development and maintenance of
      hypertension must involve a renal factor favoring sodium retention, thereby
      preventing pressure-induced natriuresis from restoring blood pressure toward
      normal levels. Since nephron numbers in the normal population range from 300,000
      to 1,100,000 or more, it was reasoned that a congenital shortfall in nephron
      endowment itself could be the renal risk factor for hypertension: demographic
      groups in whom hypertension is unusually prevalent tend to have smaller kidneys,
      implying fewer nephrons, and some inbred hypertensive rat strains have, on
      average, fewer nephrons than their respective normotensive counterparts. Recent
      independent observations in humans, relating low birth weight to both increased
      risk of hypertension in later life and the formation of fewer nephrons at birth,
      lend support to this nephron number hypothesis. Moreover, independent
      experimental studies in rodents suggest that maternal protein intake during
      gestation is directly related to the numbers of nephrons formed, and when protein
      intake is restricted, the offspring develop hypertension in maturity. The concept
      that nephron numbers may be programmed during gestation, as these observations
      imply, is discussed in relation to the potential advantages and disadvantages of
      such a mechanism for the next generation. Parallels are drawn with the
      relationship of low birth weight to pancreatic beta cell development and maturity
      onset diabetes. We suggest that the programming of fewer nephrons at birth may
      provide a fitting and overlooked explanation for the eventual development of
      hypertension in those of low birth weight.

PMID- 8743508
TI  - Pressure-volume regulation in hypertension.
AB  - In all forms of hypertension, including human essential hypertension, pressure
      natriuresis is abnormal because sodium excretion is the same as in normotension
      despite increased arterial pressure. Considerable evidence indicates that this
      resetting of pressure natriuresis plays a key role in causing hypertension,
      rather than merely occurring as an adaptation to increased blood pressure.
      Because human essential hypertension is a heterogeneous disease, it is likely
      that multiple neurohumoral and intrarenal defects contribute to abnormal pressure
      natriuresis and increased blood pressure. Physiological studies have shown that
      renal abnormalities that cause increased distal and collecting tubule
      reabsorption, decreased glomerular filtration coefficient or loss of nephrons
      also cause decreased slope of pressure natriuresis (salt-sensitive hypertension),
      whereas increased preglomerular resistance causes a parallel shift of pressure
      natriuresis (salt-insensitive hypertension). Comparison of the characteristics of
      pressure natriuresis (such as salt-sensitivity of blood pressure) in hypertensive
      subjects with those forms of experimental hypertension of known origin can
      provide insight into the etiology of human hypertension. With long-standing
      hypertension, pathological changes in the glomeruli and renal arterioles may
      further shift pressure natriuresis and exacerbate hypertension.

PMID- 8743509
TI  - Pathogenesis of primary hypertension--lessons from renal transplantation studies.

PMID- 8743510
TI  - Kidney, salt, and hypertension: how and why.
AB  - A hypothesis is proposed that the aberrant response of the tubuloglomerular
      feedback to salt load is the abnormality in the kidney in the genesis of
      essential hypertension. This thesis is based upon the following facts on the
      kidney, salt and hypertension. To effectively achieve the primary function of the
      kidney, that is, to maintain the milieu interieur or the extracellular fluids,
      the kidney must maintain a high glomerular filtration rate (GFR) and almost a
      complete tubular reabsorption in the face of limited salt intake or low ECF
      volume and in the face of changes in systemic blood pressure. Autoregulation of
      renal blood flow and GFR is therefore critical. In addition to myogenic responses
      in the resistant afferent artery, the juxtaglomerular apparatus (JGA) plays a
      crucial role in the autoregulation of renal plasma flow and GFR through
      tubuloglomerular feedback (TGF). That the JGA and TGF have appeared first in
      amphibian species in evolution suggests that the transition from aquatic sea
      life, where salt is always in excess to terrestrial life, required this
      particular structure and function of the kidney. Salt intake in the natural
      environments on land is very limited, and chronic excess salt intake is a habit
      peculiar to humans in recent culture or civilization. Thus, it is hypothesized
      that through evolution the TGF is primarily set to maintain high GFR in the face
      of low salt intake. We propose that aberrant TGF responses to salt loading may
      underlie the genesis of essential hypertension in humans. Indeed, hypertension is
      not seen in human cultures that ingest a very low salt intake.

PMID- 8743511
TI  - Antihypertensive agents and renal protection: calcium channel blockers.
AB  - This study defines the nature of the renal protective effects of calcium channel
      blockers (Ca blockers) and the effects of the Ca blocker, amlodipine, compared to
      those of the angiotensin-converting enzyme inhibitor (ACEI), enalapril, on the
      progression of renal injury in 5/6 nephrectomized spontaneously hypertensive rats
      (SHR) fed a high-salt diet. Furthermore, we studied the effects of various Ca
      blockers on the glomerular afferent and efferent arterioles using the isolated
      perfused hydronephrotic kidneys of six-week-old male Sprague-Dawley rats. In the
      first study, forty 6-week-old male SHRs which underwent 5/6 nephrectomy were
      equally divided into five groups. One group received no therapy. In two groups,
      therapy was started at four weeks post-nephrectomy, one with amlodipine and the
      other with enalapril. In the remaining two groups, amlodipine or enalapril
      therapy was started at eight weeks postnephrectomy. Amlodipine was more effective
      than enalapril in reducing proteinuria and glomerulosclerosis in the group that
      was started on drug therapy eight weeks after surgery. In the second study, at
      concentrations of 10(-6) to 10(-9) M, nifedipine, nicardipine and amlodipine
      dilated the afferent, but not the efferent, arteriole preconstricted with
      angiotensin II. On the other hand, efonidipine and manidipine clearly dilated
      angiotensin II-induced constriction of both the afferent and efferent arterioles.
      These results indicated that Ca blockers are effective at reducing renal injury
      in 5/6 nephrectomized SHR, and that they are more effective than ACEI in advanced
      stages of renal injury. The observation that only certain Ca blockers can dilate
      the efferent arteriole suggests that the renal protective effect of Ca blockers
      is not necessarily dependent on the dilation of the efferent arterioles.

PMID- 8743512
TI  - Therapeutic advantages of angiotensin converting enzyme inhibitors in chronic
      renal disease.
AB  - More than other drugs, angiotension converting enzyme (ACE) inhibitors have been
      shown to provide better control of glomerular hypertension and improved
      preservation of renal function. Long-term treatment with captopril slows the
      progression of renal impairment in diabetic nephropathy; however, the data are
      inconclusive for non-diabetic nephropathies. ACE inhibitors such as captopril,
      enalapril, alacepril delapril cilazapril, and lisinopril were equally effective
      in reducing blood pressure in multicenter clinical trials focusing on renal
      hypertension in Japan. We studied the influence of ambulatory blood pressure
      (ABP) and the effects of hypertension therapy in 104 patients with chronic renal
      glomerulonephritis as diagnosed by renal biopsy. Patients were subdivided into
      hypertensive, normotensive and hypotensive groups according to ABP and ages.
      Hypotensive subjects showed an improvement, while normotensive subjects showed a
      slower rate of progression of renal function loss than hypertensive patients.
      This suggests that the adequate ABP levels were 100 to 125/55 to 75 in those who
      were less than 40 years old, 100 to 135/60 to 80 mm Hg in patients aged 40 to 60,
      and 105 to 140/60 to 85 mm Hg in those over 60 years old. The renal protective
      effects of calcium antagonists and ACE inhibitors were associated with a
      reduction in blood pressure, but not with the hypotensive action.

PMID- 8743513
TI  - Lessons to be learned from 24-hour ambulatory blood pressure monitoring.
AB  - A number of cross sectional studies have shown that both the 24-hour average
      blood pressure value and the degree of 24-hour blood pressure variability bear a
      significant relation with the end organ damage of hypertension. Although
      longitudinal evidence of the clinical relevance of 24-hour ambulatory blood
      pressure monitoring data are scanty, the results of a recent prospective study
      have clearly shown the superiority of average 24 hour, daytime and nighttime
      blood pressure values over clinical readings in predicting the regression of left
      ventricular hypertrophy in treated hypertensive patients. Ambulatory blood
      pressure monitoring may also be useful in the evaluation of antihypertensive
      treatment, although the problem of whether ambulatory blood pressure is
      "normalized" by treatment remains still to be properly addressed. Moreover,
      currently employed discontinuous ambulatory blood pressure monitoring devices
      cannot adequately clarify the ability of antihypertensive drugs to buffer blood
      pressure variability. This interesting issue needs to be assessed in a more
      analytical fashion by means of recently developed beat-to-beat non-invasive
      ambulatory blood pressure recorders coupled with wide-band spectral analysis
      techniques.

PMID- 8743514
TI  - Blood pressure and risk of end-stage renal disease in a screened cohort.
AB  - We prospectively studied a total of 107,192 subjects over 18 years of age (51,122
      men and 56,070 women) who participated in dipstick urinalyses and blood pressure
      measurements in 1983. The subjects represented approximately 13.7% of the entire
      Okinawan adult population of 780,000 according to the 1980 Census. Independently,
      data for all dialysis patients registered from April 1, 1983 to March 31, 1994
      were analyzed; the total number of end-stage renal disease (ESRD) dialysis
      patients was 2,009 (1,126 men and 883 women) during the study period. Dialysis
      patients who had been in the 1983 mass screening and who later required dialysis
      during the study period were identified and verified by reviewing the medical
      records. ESRD developed in 193 (105 men and 88 women) participants from the 1983
      health screening. In this mass screening setting, high diastolic blood pressure
      was identified as the significant predictor of ESRD with an adjusted odds ratio
      of 1.39 and a 95% confidence interval of 1.17 to 1.64.

PMID- 8743515
TI  - The role of arterial hypertension in progression of renal failure.
AB  - The effect of arterial hypertension on the progression of chronic renal failure
      (CRF) was evaluated in 108 patients who eventually required dialysis in the 8
      year period of the study. Patients' average serum creatinine (SCr) concentration
      at first examination was 239.7 +/- 45.3 mumol/liter and at the start of dialysis
      was 1,661.0 +/- 181.9 mumol/liter. The mean duration of pre-dialysis follow-up
      was 53.7 +/- 15.7 months. The mean monthly increase in SCr was 18.8 +/- 13.4 and
      2.1 +/- 1.4 mumol/liter/month in hypertensive and normotensive CRF patients,
      respectively (P < 0.001). The CRF patients with a diastolic blood pressure (BP) <
      89 mm Hg had a significantly (P < 0.05) slower rate of decline in renal function
      than the patients with a diastolic BP > or = 90 mm Hg. There was a significant
      relationship between a mean diastolic BP > or = 90 mm Hg and the rate of monthly
      increase in SCr (r = 0.81, P < 0.001). These data indicate that control of
      diastolic BP in CRF patients is a potentially effective way to slow the rate of
      decline in renal function.

PMID- 8743516
TI  - Blood pressure and progression of renal failure in the elderly.
AB  - There are a lack of studies about elderly patients with chronic renal failure
      (CRF). We studied 22 patients, aged 64 to 74 years, who were diagnosed with
      hypertensive nephropathy (HN), defined as a diastolic blood pressure (DBP) < 95
      mm Hg and a basal creatinine clearance (CCr) of 52 +/- 6 ml/min/1.73 m2. During
      the minimum two-year follow-up, the progression of renal failure (RF) was
      analyzed by the plotted slope of CCr versus time. Patients were divided into two
      groups, each administered one of two different drugs, Ca antagonists (group I)
      and angiotensin converting enzyme (ACE) inhibitors (group II). The DBP in both
      groups was lowered by the end of the study. The mean arterial pressure (MAP) was
      less in group I (97.35 +/- 5.98 mm Hg) than in group II (108.3 +/- 9.95 mm Hg).
      The decline in renal function was a mean rate of -0.62 +/- 0.36 ml/min/month in
      group I and -1.03 +/- 0.17 ml/min/month in group II. In conclusion, we show that
      patients who were on ACE inhibitors exhibited a greater MAP and a greater decline
      in renal function compared with the patients who were on Ca antagonist therapy.
      We also found that patients who were younger than 70 years old had better control
      of their blood pressure rates and less of a rate of decline in renal function
      than their older counterparts.

PMID- 8743517
TI  - Renal effects of prolonged antihypertensive treatment with diltiazem.
AB  - The effects of diltiazem (DTZ) treatment on blood pressure, renal function and
      renal hemodynamics over a six week period of therapy were evaluated in 14 adult
      patients with mild to moderate hypertension. Their creatinine clearances were 64
      to 153 ml/min. After a week of treatment with placebo, DTZ was administered
      orally at a daily dose of 120 mg b.i.d. Blood pressure decreased from a mean
      value of 152/99 mm Hg (+/-13/6 SD) up to 144/91 (+/-17/8, P < 0.005) in the
      supine position and from 149/107 (+/-14/9) to 141/96 (+/-16/9, P < 0.005) in
      standing position. Heart rate decreased from 74 (+/-9) to 69 (+/-8). Plasma urea,
      creatinine, uric acid and their clearances as well as GFR and ERPF remained
      stable throughout the trial. Plasma glucose increased from 81 (+/-15) mg/dl to 98
      (+/-30, P < 0.05) and plasma potassium decreased from 4.0 mEq/liter to 3.7 (+/
      0.3, P < 0.005). Plasma cholesterol and triglycerides were unmodified. DTZ is an
      effective antihypertensive agent which does not significantly affect renal
      function. The effects on plasma glucose and potassium require periodical check
      ups of these parameters.

PMID- 8743518
TI  - Microalbuminuria, left ventricular mass and ambulatory blood pressure in
      essential hypertension.
AB  - The objective of the present study was to assess the relationship between
      microalbuminuria (Malb) and left ventricular hypertrophy (LVH), when levels of
      ambulatory BP was token in to account as a confounder factor. Patients with
      essential hypertension, aged 25 to 50 years old, never treated with
      antihypertensive drugs, were included in the study. The inclusion criteria were:
      (a) absence of diabetes, renal disease or urinary tract infection; (b) urinary
      albumin excretion (UAE) estimated in urine of 24 hours in two separate days; (c)
      echocardiography suitable for measurement of left ventricular mass (LVM); and (d)
      good quality ambulatory blood pressure monitoring during 24 hours. UAE was
      measured using a immunonephelometric assay (Behring Institute) and Malb was
      considered when UAE 30 to 300 mg/24 hours during the two days. LVM was calculated
      by the Devereaux formula and referred to height (LVMI g/m). AMBP was performed
      using an oscilometric device (Spacelabs 90202 or 90207) during a regular working
      day. Readings were programmed every 20 minutes between 6 a.m. to midnight and
      thereafter every 30 minutes. The average BP during a 24 hour period was
      calculated. One hundred and fifty one patients (96 male, mean age 37 +/- 8 years,
      body mass index 27.7 +/- 3.7 g/m2) were included. The average values of office BP
      was 148 +/- 15/96 +/- 8 mm Hg, and the average BP during 24 hours was 137 +/-
      13/88 +/- 12 mm Hg. UAE was 30.1 +/- 52.3 mg/24 hr and the LVMI 140.6 +/- 44.1
      g/m. The percentage of Malb patients was 28% and those with LVH 34%. A
      significant relationship between UAE and office and ambulatory SBP and DBP was
      observed. LVMI was also significantly related to ambulatory SBP and DBP, a
      relationship that was not found for office BP. In a multiple regression model,
      significant relationship between UAE and LVMI emerged, independent of diastolic
      ambulatory BP, age and sex (P < 0.04). In conclusion; we observed a significant
      relationship between UAE and LVMI, in part, independent of blood pressure. The
      fact that Malb is associated with the presence of LVH, supports the idea that
      Malb is a risk marker in essential hypertensive patients.

PMID- 8743519
TI  - Nitrendipine and enalapril in the treatment of diabetic hypertensive patients
      with microalbuminuria.
AB  - A trial to study the efficacy, safety and tolerability of nitrendipine and
      enalapril in the treatment of diabetic hypertensive patients with
      microalbuminuria (MA) was performed to compare the effects of both drugs in the
      prevention of the renal impairment. Twenty-eight valid patients [13 with
      nitrendipine (N) and 15 with enalapril (E) with NIDDM, hypertension (diastolic
      blood pressure between 90 to 114 mm Hg) and MA (urinary albumin between 30 to 300
      mg/24 hr) were recruited in a double blind, randomized trial. Following a placebo
      run-in period of two to four weeks, all eligible patients were randomly allocated
      to either N or E treatment. Treatment lasted six months, with two different
      visits at three and six months in which blood pressure (BP), heart rate (HR),
      renal function and MA were measured. No statistically significant differences on
      BP and metabolic parameters were found between both treatment groups. The
      geometric mean of final glomerular filtration rate (GFR) in the N group was 34.5%
      higher than in the E group, while the reduction on MA was most important in the E
      group. Eleven patients reported adverse events (AEs) and there were four
      dropouts, three of them due to AEs. We conclude that both treatments are a good
      choice for treating diabetic hypertensive patients with early altered renal
      function, as they reduce BP without altering metabolic parameters, increase GFR
      and reduce MA with a low frequency of AEs.

PMID- 8743520
TI  - Renal function changes in hypertensive patients with non-insulin- dependent
      diabetes mellitus.
AB  - A group of 146 patients with non-insulin- dependent diabetes mellitus (NIDDM) was
      studied. They were divided into two groups of 73 age and sex matched patients,
      according to the presence or absence of hypertension. We recorded the presence of
      macrovascular and microvascular complications of NIDDM, family history, body mass
      index (BMI), glycemic control and lipidic profile. Renal parameters included
      plasma creatinine, urinary albumin excretion rate (UAER), glomerular filtration
      rate (GFR), effective renal plasma flow (ERPF) and filtration fraction.
      Hypertensive patients had a higher BMI (30 +/- 4.8 kg/m2 vs. 27.6 +/- 4.4 kg/m2,
      P < 0.005), total cholesterol (6.34 +/- 1.47 mmol/l vs. 5.72 +/- 1.14 mmol/liter,
      P < 0.01), creatinine (91.1 +/- 25.6 mumol/liter vs. 81.3 +/- 20.3 mumol/liter, P
      < 0.05) and UAER [63.7 (range 1 to 5160) mg/24 hr vs. 27.3 (3 to 5500) mg/24 hr,
      P < 0.001]. GFR was lower in the group with hypertension (113 +/- 35 ml.min
      1.1.73 m-2 vs. 127 +/- 29 ml.min-1.1.73 m-2, P < 0.05), but there were no
      differences in ERPF. The difference in GFR was only apparent in patients without
      established diabetic nephropathy. Hypertensive patients had higher frequency of
      ischemic heart disease (18% vs. 6%, P < 0.05) and diabetic nephropathy (62% vs.
      38%, P < 0.005). We conclude hypertensive NIDDM patients, when compared with
      normotensive NIDDM patients, are more obese, hypercholesterolemic and have a
      higher frequency of ischemic heart disease and diabetic nephropathy. Hypertensive
      NIDDM patients have a worse renal function than normotensives before clinical
      proteinuria appears. The deterioration of GFR in hypertensive NIDDM patients
      possibly has an important influence on the progression of diabetic nephropathy.

PMID- 8743521
TI  - Nitrendipine and enalapril improve albuminuria and glomerular filtration rate in
      non-insulin dependent diabetes.
AB  - The effects of 3, 15, and 27 months of treatment with nitrendipine (10 to 40
      mg/day) and enalapril (5 to 20 mg/day) on diastolic blood pressure (DBP),
      overnight urinary albumin excretion (UAE) rate, glomerular filtration rate (GFR),
      and renal plasma flow (RPF) were studied prospectively in a parallel group design
      in 13 microalbuminuric non-insulin dependent diabetic patients with mild
      hypertension and biopsy-proven diabetic glomerulopathy. Throughout the study
      period DBP decreased in both groups to < 95 mm Hg. At three months UAE, GFR, and
      RPF did not change significantly. At 15 and 27 months UAE (microgram/min,
      geometric mean and 95% C.I.) decreased respectively from 47.4 (23.4 to 95.9) to
      28.6 (10.3 to 79.4), and to 22.3 (10.9 to 45.2; P = 0.0005) with nitrendipine,
      and from 58.3 (30.3 to 110.9) to 44.1 (22.9 to 84.8), and to 14.7 (4.4 to 49.3; P
      = 0.0025) with enalapril. Four patients in each group were normoalbuminuric at 27
      months and none became macroalbuminuric. At 15 months the GFR (ml/min/1.73 m2,
      mean +/- SD) increased from 69.5 +/- 15.2 to 96.6 +/- 22.0 (P < 0.05) with
      nitrendipine and from 58.9 +/- 10.7 to 78.5 +/- 11.0 (P < 0.05) with enalapril.
      At 27 months the GFR was still numerically higher that at baseline either with
      nitrandipine (81.2 +/- 7.8) and with enalapril (79.9 +/- 17.7) (P = 0.7). The RPF
      (ml/min/1.73 m2, mean +/- SD) at baseline and at 27 months was comparable either
      with nitrendipine (456.6 +/- 165.3 vs. 400.9 +/- 112.9) and with enalapril (400.3
      +/- 81.3 vs. 399.0 +/- 123.7). Both treatments were well tolerated. This is the
      first evidence that long-term effective control of arterial blood pressure by a
      calcium channel blocker or by an angiotensin converting enzyme inhibitor, in
      addition to reducing albuminuria, also improves GFR in incipient nephropathy.

PMID- 8743522
TI  - Improvement in renal function by felodipine during cyclosporine treatment in
      acute and short-term studies.
AB  - The purpose was to study whether the calcium entry blocker, felodipine, could
      reduce the nephrotoxic and hypertensive effect of cyclosporine. The effect of
      felodipine on glomerular filtration rate (GFR), renal plasma flow (RPF),
      fractional excretion of sodium, lithium clearance and blood pressure was measured
      in three randomized, placebo-controlled studies of cyclosporine treated patients.
      In study one, 10 renal transplant recipients were examined within the first six
      months after transplantation in a cross-over design. Renal hemodynamics were
      determined after the acute ingestion of felodipine or placebo, with an interval
      of less than one week between the two examinations. In study two, 79 renal
      transplant recipients were randomized to a treatment with felodipine or placebo
      just before transplantation, and renal hemodynamics were determined after twelve
      weeks. In study three, 18 patients, who were treated with cyclosporine due to
      dermatological diseases, were examined in a cross-over design to determine their
      renal hemodynamics after four weeks of treatment with felodipine or placebo.
      Felodipine increased renal hemodynamics in study one (GFR 16%, RPF 33%, P < 0.01
      for both), in study two (GFR 23%, RPF 28%, P < 0.05 for both), and in study three
      (GFR 13%, RPF 26%, P < 0.01 for both). FE(Na) was significantly increased by
      felodipine in studies one and three, but not in study two. Lithium clearance was
      significantly increased and blood pressure significantly reduced by felodipine in
      all three studies. It can be concluded that felodipine counteracts both the
      cyclosporine induced impairment in renal hemodynamics and the increase in blood
      pressure in acute and short-term studies.

PMID- 8743523
TI  - Renal hemodynamics in hypertensive renal allograft recipients: effects of calcium
      antagonists and ACE inhibitors.
AB  - Hypertension present in more than 50% of successfully renal transplanted patients
      and its prevalence has slightly increased since the introduction of cyclosporine
      A. Twenty patients, 9 women and 11 men aged from 30 to 58 years, with stable
      cadaveric renal allograft function and moderate to severe hypertension, were
      included in the study. Renal artery graft stenosis causing hypertension were
      excluded. All patients were given triple drug immunosuppressive treatment with
      methylprednisolone, azathioprine and cyclosporine A (CsA) and their hypertension
      was treated with a nifedipine dose of 20 mg twice daily. To evaluate the effect
      of ACE inhibitors on renal hemodynamics and hypertension, a 4 mg/daily dose of
      perindopril was added to the above regimen for two months. Effective renal plasma
      flow (ERPF) decreased from 208 +/- 54 to 168 +/- 61 ml/min and renal vascular
      resistance (RVR) increased from 75 +/- 12 to 88 +/- 17 mm Hg/ml/min (P < 0.05 and
      P < 0.01, respectively). Mean blood pressure was significantly (P < 0.001)
      reduced by the combination of both agents in comparison to the blood pressure
      control by monotherapy with nifedipine. It is suggested that the combination of
      both antihypertensive agents was more effective than monotherapy with nifedipine
      in controlling blood pressure, but less favorable on the renal hemodynamic
      response in hypertensive renal transplant patients who were maintained on CsA.

PMID- 8743524
TI  - Angiotensin I-converting enzyme insertion/deletion polymorphism: potential
      significance in nephrology.
AB  - Angiotensin I-converting enzyme (ACE) plays a pivotal role in cardiovascular
      homeostasis and by activating angiotensin I into angiotensin II and inactivating
      bradykinin. These two peptides play antagonistic roles on the cardiovascular
      system by regulating vascular tone and vascular smooth muscle cell proliferation.
      Identification of the ACE gene as a genetic marker for various forms of
      cardiovascular disease is a recent result of the progress made in molecular
      biology and genetics. The insertion/deletion (ID) polymorphism of the ACE gene
      defined by the presence or absence of the 287 base pair Alu sequence situated in
      intron 16 has been investigated as a possible genetic marker for a variety of
      cardiovascular disease including myocardial infarction, essential hypertension,
      cardiomyopathy, and diabetic vascular complications. This paper reviews prior
      reports and briefly describes our recent study on the association of the ACE I/D
      polymorphism and antiproteinuric effect of ACE inhibitors in patients with
      proteinuria.

PMID- 8743525
TI  - Quinapril ACE-inhibition effects on adrenergic parameters in moderate essential
      hypertension.
AB  - The effects of inhibition of the renin-angiotensin system with quinapril on
      adrenergic transmission were determined in 18 patients with moderate essential
      hypertension. Plasmatic renin activity, catecolamines, and aldosterone as well as
      vascular reactivity after norepinephrine and angiotensin II perfusion were
      determined before and after treatment with the ACE inhibitor quinapril up to 40
      mg/day during four months. In the responder patients (patients with a casual
      diastolic blood pressure decrease > 5 mm Hg determined at the beginning of the
      second vascular reactivity study, (N = 9) a decrease of plasma norepinephrine and
      epinephrine and a slight increase of vascular reactivity was found. Non-responder
      patients (N = 9) did not show any significant changes in these parameters. These
      results demonstrate that the hypotensive effect of quinapril may be related not
      only to the inhibition of RAS, but also to the blockage of the adrenergic system.

PMID- 8743526
TI  - Antihypertensive activity and renal effects of benazepril in humans.
AB  - The effects of the treatment with benazepril (BEN) on blood pressure and renal
      function have been evaluated in nine adult patients affected by mild to moderate
      hypertension. BEN was administered orally, at a single daily dose of 10 mg for
      four weeks. BEN induced a clinically significant decrease in blood pressure, from
      a mean basal value of 155/98 mm Hg (+/- 15/7 SD) to 146/92 (+/- 12/9) after seven
      days of therapy and 139/88 (+/- 11/10) after 28 days in supine position and from
      152/104 (+/- 17/6) to 144/97 (+/- 14/6) after seven days and 145/99 (+/- 16/9)
      after 28 days in a standing position. Plasma urea, creatinine, uric acid and
      their clearances as well as urine enzymes (GGT, ALP, LDH) remained stable
      throughout the duration of the therapy. GFR showed a modest increase, from 61.3
      +/- 13.2 ml/min to 65.3 +/- 18.3 ERPF showed a slightly more evident increase,
      from 246.7 +/- 68.1 ml/min to 276.9 +/- 75.6. Plasma levels of glucose,
      cholesterol and triglycerides were not influenced by BEN. Plasma potassium
      increased from 4.0 +/- 0.3 to 4.4 +/- 0.5 mEq/liter. The results of this study
      indicate that BEN is a safe and effective antihypertensive agent that does not
      cause any adverse renal or metabolic effects.

PMID- 8743527
TI  - Involvement of angiotensin II in glomerulosclerosis of stroke-prone spontaneously
      hypertensive rats.
AB  - Renal plasma flow (RPF), glomerular filtration rate (GFR), glomerular pathology
      and glomerular TGF-beta gene expression were examined in 12- and 24-week-old
      stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY).
      These parameters were also examined in SHRSP treated with equihypotensive doses
      of angiotensin II receptor antagonist (CV-11974:CV) and hydralazine (Hyd) for 12
      weeks. Twelve-week-old SHRSP showed a decrease in RPF and GFR, and an increase in
      filtration fraction (FF) and urinary protein excretion (UP) compared to WKY. CV
      normalized these parameters, whereas although Hyd showed improved levels they
      were not to the levels achieved by the WKY. Glomerular TGF-beta expression was
      increased 2.0-fold in 12- and 24-week-old SHRSP, and CV, but not Hyd, decreased
      it to the control levels of WKY. At 24 weeks old, SHRSP showed a higher
      glomerulosclerosis index (GI) than WKY. CV, but not Hyd, lowered the GI to the
      level of the WKY controls. These data indicate that renal hemodynamic changes are
      closely associated with an increased TGF-beta expression in SHRSP and that this
      condition is caused by angiotensin II.

PMID- 8743528
TI  - Losartan protects the rat kidney from ischemic injury.
AB  - Administration of losartan (L), an angiotensin II receptor antagonist, at a daily
      dose of 3 mg/kg body wt, lowered systolic blood pressure (SBP) in both the Prague
      hypertensive rat and the Prague normotensive rat (PNR). Proteinuria was markedly
      reduced in both strains by L. Seven days after kidney ischemia due to bilateral
      clamping of both renal arteries for 45 minutes, the renal function (endogenous
      creatinine clearance, sodium, potassium, and urea excretion rates) was completely
      normal in L-treated PHR and PNR, whereas distinct deterioration was observed in
      untreated animals. The survival rate after kidney ischemia was significantly
      improved by L in both PHR and PNR. Thus, L had a significant blood pressure
      lowering action in both strains and exerted a distinct renal protective effect
      from kidney ischemia.

PMID- 8743529
TI  - TCV-116 inhibits renal interstitial and glomerular injury in glomerulosclerotic
      rats.
AB  - TCV-116 and enalapril were given in two stages: (early phase) for 6 to 10 weeks
      to 5/6 nephrectomized (NX) rats two weeks after nephrectomy, 12-week-old Wistar
      fatty (WF) rats and 7-week-old spontaneously hypercholesterolemic (SHC) rats; and
      (late phase) for 6 to 16 weeks to 5/6 NX rats 11 weeks after nephrectomy, 27-week
      old WF rats and 10-week-old SHC rats. Urinary albumin, blood pressure (BP),
      glomerular filtration rate (GFR) and renal histology were examined. In the early
      phase, both agents inhibited proteinuria and tended to inhibit
      glomerulosclerosis. TCV-116 also inhibited interstitial inflammation. The
      antiproteinuric effects did not necessarily correlate with the BP-lowering
      effects. In the late phase, both agents showed equal antiproteinuric and
      antihypertensive effects. In 5/6NX and WF rats, TCV-116 inhibited
      tubulointerstitial inflammation/fibrosis, glomerulosclerosis and renal
      dysfunction, but enalapril had little effect on these parameters. In the SHC
      rats, TCV-116 inhibited renal tubulointerstitial inflammation and
      glomerulosclerosis, but enalapril inhibited only glomerulosclerosis. After drug
      administration, there was a positive correlation between proteinuria and BP, and
      a negative correlation between the severity of tissue damage and GFR, but not BP.
      These findings suggest that initial BP-independent tubulointerstitial
      inflammation may enhance glomerulosclerosis in the late phase, and TCV-116 might
      prevent the development of glomerulosclerosis through inhibition of angiotensin
      II-mediated tubulointerstitial damage in these models.

PMID- 8743530
TI  - Role of endothelins for renin regulation.
AB  - Endothelins 1, 2, and 3 did not affect basal renin secretion, but selectively
      inhibited to a similar extent both cAMP-stimulated renin secretion and renin gene
      expression in isolated renal juxtaglomerular cells. In isolated perfused rat
      kidneys and after cAMP-stimulated renin secretion using isoproterenol,
      endothelins inhibited basal renin secretion at a perfusion pressure of 80 mm Hg.
      Endothelin's main action is mediated via the endothelin ETB receptor. It involves
      activation of phospholipase C, intracellular calcium mobilization in
      juxtaglomerular cells that is dependent on extracellular calcium and associated
      with prominent calcium-activated chloride currents, and subsequent processes. In
      normal rats and in rats with unilateral renal artery clips, a nonselective
      inhibitor of endothelin receptors, Ro 47-0203, did not significantly change renin
      secretion and renal renin gene expression, despite complete abolition of the
      vasoconstrictive and renin inhibitory action of exogenous endothelins by this
      drug in isolated perfused rat kidneys. In spite of a marked renin inhibitory
      efficacy of exogenous endothelins in vitro (isolated renal juxtaglomerular cells,
      isolated perfused rat kidney), endogenous endothelins play no relevant regulatory
      role in renin secretion and renin gene expression in normal and hypoperfused rat
      kidneys in vivo. However, endothelins may be of physiological relevance for the
      development of hypertension upon renal artery stenosis.

PMID- 8743531
TI  - Ionic effects of angiotensin II and their role in the activation of the Na+/H+
      antiporter.
AB  - The possible interdependence of the effects of angiotensin II (Ang II) on
      intracellular pH (pHi), free cytosolic calcium (Cai2+) and free cytosolic sodium
      (Nai+) was studied in cultured vascular smooth muscle cells (VSMC) from rat
      aorta. Cells were loaded with either BCECF/AM, SBFI/AM or Fura-2 for measurement
      of pHi, Nai+ or Cai2+, respectively. Superfusing with a HEPES solution containing
      Ang II (1 microM) caused a progressive increase in Nai+. Concurrent pHi changes
      measured in parallel experiments showed that Ang II caused a brief cell
      acidification followed by a delayed alkalinization, which is due to activation of
      the Na+/H+ antiporter. Concurrent Cai2+ changes measured in parallel experiments
      showed that Ang II caused a prompt rise in Cai2+ with a peak response at
      approximately 30 seconds followed by a rapid recovery. Obliteration of the Ang II
      induced rise in Cai2+ using a Ca2+ chelator (BAPTA), prevented the initial cell
      acidification but did not prevent the delayed rise in pHi, which reflects
      stimulation of the Na+/H+ antiporter. Our data thus show that in cultured VSMC
      neither the rise in Cai2+ nor the fall in pHi caused by Ang II is a total
      prerequisite for activation of the Na+/H+ antiporter by this agonist.

PMID- 8743532
TI  - Aging abolishes the renal response to L-arginine infusion in essential
      hypertension.
AB  - A defect in the endothelium-dependent vasorelaxation could contribute to the
      development of arterial hypertension through the facilitation of renal
      vasoconstriction and sodium retention. In this study, we tested the hypothesis
      that aging impairs kidney function in essential hypertension through a
      derangement of nitric oxide-dependent renal mechanisms. To this end, we compared
      the renal response to an intravenous infusion of the precursor of nitric oxide
      synthesis, L-arginine, in young and aged essential hypertensives. In young
      hypertensives, L-arginine induced a significant increase in renal plasma flow,
      glomerular filtration rate, natriuresis and kaliuresis, without changes in
      filtration fraction. These effects were not observed in aged hypertensives.
      Neither PRA nor PA were affected by L-arginine infusion in any group. These
      results indicate that aging produces a derangement of endothelial function in
      essential hypertension.

PMID- 8743533
TI  - Vasoconstriction of the afferent arteriole and defective renal synthesis of
      nitric oxide in essential hypertension.
AB  - This study was designed to investigate whether some relation exists between
      afferent arteriolar resistance (AAR) and the renal production of nitric oxide
      (NO) and prostacyclin (PGI2) in 21 patients with untreated essential hypertension
      and 20 normotensive controls. All subjects were studied in conditions of an
      unlimited Na+ diet both basally and after a four-hour amino acid infusion. AAR
      was calculated using Gomez's equations. Renal production of NO and PGI2 were
      assessed by radioimmunoassay of the urinary excretion of cGMP and 6-keto-PGF1
      alpha, respectively. Baseline AAR was higher (P < 0.01) in hypertensives than in
      normotensives. The baseline urinary excretion of 6-keto-PGF1 alpha and cGMP were
      similar in the two groups of subjects. AAR diminished (P < 0.005) in
      normotensives and remained unchanged in hypertensives after amino acid infusion.
      Urinary excretion of 6-keto-PGF1 alpha was increased similarly in the two groups
      of subjects after infusion. Urinary excretion of cGMP remained unchanged in
      normotensives and decreased by 31% in hypertensives after infusion. These
      findings suggest that afferent vasoconstriction present in hypertensive patients
      is unresponsive to the vasodilatory manoeuvre of amino acid infusion. This lack
      of response may be due to a defective renal synthesis of NO in these patients.

PMID- 8743534
TI  - Diverse effects of calcium antagonists on glomerular hemodynamics.
AB  - This study examined the direct effects of calcium antagonists on glomerular
      hemodynamics. Rabbit afferent (Af-) or efferent arterioles (Ef-Arts) were
      microperfused in vitro at constant pressure. Ef-Arts were perfused from the
      distal end of Af-Art through the glomerulus. Increasing doses (10(-10) to 10(-7)
      M) of nifedipine (Nif), nicardipine (Nic) or manidipine (Man) were added into the
      lumen of Af- or Ef-Arts preconstricted (by about 40%) with norepinephrine.
      Although Nif and Nic dilated Af-Arts in a dose-dependent manner, they did not
      cause any dilation in Ef-Arts. In contrast, Man dilated both Af- and Ef-Arts in a
      dose dependent manner; Man at 10(-7) M dilated Af- and Ef-Arts by 71 +/- 12% (N =
      7) and 38 +/- 3% (N = 6), respectively. Although Man's dilator effect on Ef-Art
      was not affected by inhibiting nitric oxide (NO) synthesis (N = 6), it was
      markedly attenuated by eliminating the influence of glomerulus (14 +/- 3% by Man
      at 10(-7) M, N = 5). These results demonstrate that in addition to dilating Af
      Art, Man, but not Nif or Nic, dilates Ef-Art through a glomerulus-derived
      vasodilator(s) other than NO. Such diverse actions should be taken into
      consideration when calcium antagonists are used in the treatment of patients with
      cardiovascular and renal diseases.

PMID- 8743535
TI  - Role of endogenous endothelin and nitric oxide in tubuloglomerular feedback.
AB  - To elucidate the roles of endogenous endothelin (ET) and nitric oxide (NO) in
      tubuloglomerular feedback (TGF), the effects of FR139317, a specific ET-A
      receptor antagonist, and NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor on
      TGF were studied in Sprague-Dawley rats. FR139317 (1.5 mg/kg/hr i.v.) reversed
      the systemic pressor and renal vasoconstrictor responses induced by ET-1 (2
      nmol/kg/hr i.v.), but did not alter the early proximal flow rate (EPFR) reduction
      in response to a loop perfusion with an artificial tubular fluid at 40 nl/min (47
      +/- 3 vs. 47 +/- 3% in controls). L-NNA (0.2 mg/kg + 2 micrograms/kg/min i.v.)
      had no effect on systemic blood pressure (BP), renal hemodynamics or EPFR
      measured at zero perfusion (31 +/- 2 vs. 31 +/- 2 nl/min in controls), but
      enhanced the EPFR reduction during loop perfusion to 77 +/- 3%. Loop perfusion
      with 10(-3) M L-NNA in perfusate also increased the EPFR reduction to 70 +/- 7%.
      In conclusion, inhibition of NO synthesis enhances the TGF-mediated reduction of
      nephron GFR. This indicates an active participation of endogenous NO in the
      control of afferent arteriolar tone. endogenous ET does not influence TGF via the
      ET-A receptor.

PMID- 8743536
TI  - Effects of antihypertensive drugs on nitric oxide synthase activity in rat
      kidney.
AB  - Nitric oxide production has been reported to be reduced in hypertensive patients.
      In this study, we investigated the effects of antihypertensive drugs such as
      calcium channel blocker, amlodipine, alpha 1-adrenoceptor blocker, doxazosin and
      angiotensin converting enzyme (ACE) inhibitor, imidapril on nitric oxide synthase
      (NOS) activity in the kidneys of L-NAME-induced hypertensive rats. An increased
      blood pressure in L-NAME-induced hypertensive rats was significantly decreased by
      these antihypertensives to the same extent at four weeks. Nitrite production from
      the kidney slices was significantly suppressed in L-NAME-induced hypertensive
      rats. This suppression of nitrite production was reversed to the control level in
      the rats treated with amlodipine, and significantly enhanced by doxazosin and
      imidapril. Immunoreactivity for both the brain-type NOS in the macula densa and
      endothelial cell-type NOS in renal vasculature was diminished in L-NAME rats, and
      antihypertensive therapies, especially doxazosin and imidapril, increased NOS
      immunostaining. The increased glomerulosclerosis score in the L-NAME group was
      significantly lowered by the treatment with doxazosin and imidapril. In
      conclusion, a decreased NOS activity in L-NAME-induced hypertensive rats was
      significantly increased by alpha 1-adrenoceptor blockers and ACE inhibitors in
      the kidney, and this increased NOS activity may have a role in the prevention of
      glomerulosclerosis.

PMID- 8743537
TI  - Chronic effects of nitric oxide and prostaglandin inhibition on pressure diuresis
      and natriuresis in rats.
AB  - The long-term interaction between nitric oxide (NO) and prostaglandins (PGs) in
      the pressure diuresis and natriuresis response has been studied. Experiments were
      performed in rats with chronic (8 weeks) inhibition of NO (NG-nitro L-arginine
      methyl Ester, L-NAME, 40 mg/kg/day) with or without simultaneous PGs synthesis
      blockade (indomethacin, 1 mg/kg/day). A time control group with no treatment was
      studied in parallel. At the end of this period, the animals were anesthetized and
      renal hemodynamics and excretion were studied at three levels of renal perfusion
      pressure (RPP; 100, 125 and 150 mm Hg). Renal blood flow, glomerular filtration
      rate, diuresis and natriuresis were lower at the three RPP levels in both L-NAME
      treated groups than in the control or indomethacin-treated animals. Simultaneous
      administration of indomethacin plus L-NAME did not further modify the hemodynamic
      or excretory responses observed in the L-NAME-treated animals. These results show
      that chronic NO inhibition impairs the renal excretory response to changes in
      renal perfusion pressure, and simultaneous NO and prostaglandin synthesis
      inhibition does not reduce those responses further. It is concluded that, on a
      long-term basis, a preserved NO production, but not prostaglandin production, is
      critical for a normal pressure diuretic and natriuretic mechanism.

PMID- 8743538
TI  - C-type natriuretic peptide in chronic renal failure and its action in humans.
AB  - We have previously reported that C-type natriuretic peptide (CNP), the third
      member of the natriuretic peptide family, is produced in vascular endothelial
      cells and acts as an endothelium-derived relaxing peptide. To clarify the
      clinical significance of CNP in renal disorders, we examined the plasma level of
      CNP in patients with various cardiovascular diseases, including chronic renal
      failure (CRF) patients who were under hemodialysis therapy. We also investigated
      biological effects of intravenously-administered CNP (0.43 nmol/kg) by bolus
      injection from the peripheral vein in healthy volunteers and measured systemic
      hemodynamic variables, plasma levels of CNP, atrial natriuretic peptide (ANP),
      brain natriuretic peptide (BNP), cGMP, aldosterone and also urine volume, urinary
      excretions of sodium, potassium, chloride and cGMP. The plasma CNP levels in
      healthy humans (N = 13) was 1.4 +/- 0.6 fmol/ml. In CRF patients, the plasma CNP
      significantly increased up to 3.0 +/- 1.1 fmol/ml. The administration of CNP
      elicited significant increase of plasma cGMP level (from 4.77 +/- 1.25 to 8.33 +/
      1.59 pmol/ml 15 min after the administration) and of urinary cGMP excretion
      (from 30.7 +/- 4.3 to 74.9 +/- 13.4 nmol/30 min). Intravenously-administered CNP
      exerted significant diuretic (% increase: +117 +/- 85.0), natriuretic,
      kalliuretic and chloriuretic actions with the increase of endogenous creatinine
      clearance. CNP also elicited significant hypotensive actions (delta BPs/delta
      BPd: -4.3 +/- 1.3/-4.1 +/- 1.0 mm Hg) with the concomitant increase of heart rate
      (+7.6 +/- 2.6 bpm). Plasma aldosterone concentration significantly decreased from
      45.4 +/- 2.3 to 35.4 +/- 4.9 pg/ml 30 minutes after the administration. Taken
      together, these results suggest a role for CNP in human renal function.

PMID- 8743539
TI  - Adrenomedullin and proadrenomedullin N-terminal 20 peptide in impaired renal
      function.
AB  - Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide
      found in the N-terminal portion of the prohormone of adrenomedullin (AM), a
      vasodilator peptide. In this study, we examined the pathophysiological roles of
      the two peptides. Plasma concentrations of both peptides in patients with
      impaired renal function were measured and compared to those of the control
      subjects. Plasma AM concentrations in the study patients were significantly (P <
      0.01) higher than in the controls with a serum creatinine of < 1 mg/dl (2.94 +/-
      0.18 fmol/ml), and higher concentrations in those patients with a serum
      creatinine of > or = 2 mg/dl (Group II; 14.8 +/- 1.9 fmol/ml) were observed as
      compared to those at the 1 to 2 mg/dl level (Group I; 10.3 +/- 1.2 fmol/ml).
      Similarly, plasma PAMP concentrations tended to be higher in the Group I patients
      (0.82 +/- 0.05 fmol/ml) and significantly (P < 0.01) increased in the Group II
      patients (1.42 +/- 0.17 fmol/ml) when compared to the controls (0.53 +/- 0.04
      fmol/ml). A significantly (P < 0.05) positive correlation was noted between the
      plasma AM and PAMP in the study patients. These findings suggest a potential role
      for these biologically active peptides in the regulation of blood pressure in
      impaired renal function.

PMID- 8743540
TI  - Sodium balance and hypertension in obese and fatty rats.
AB  - To investigate the role of sodium in obesity induced hypertension, Wistar fatty
      rats (WFR) were employed. This rat has the following characteristics: (1)
      hyperglycemia, (2) hyperinsulinemia, and (3) hypertriglycemia. Four percent
      sodium chloride with constant amount of food intake was administered to these
      rats from 8 to 16 weeks. During this period, body wt, food intake, water
      consumption, urine volume, systolic blood pressure, urinary excretion of sodium
      and potassium, urinary albumin excretion, plasma sodium and potassium, and plasma
      glucose and immunoreactive insulin (IRI) were measured before, and twice more
      during eight weeks. No remarkable changes were observed in plasma glucose level
      during these periods between the two groups. On the other hand, in group 1 IRI
      significantly increased compared with group 2. Mean blood pressure was increased
      from 110 +/- 5 to 130 +/- 8 mm Hg (P < 0.01). To ascertain whether this salt
      sensitivity relates to the abnormalities in pressure-natriuresis responses, the
      pressure-natriuresis (P-N) was characterized. The P-N curve in WFR was shifted to
      the right and its slope was flattened compared to its control Wistar lean rats.
      In conclusion, an excess of dietary sodium intake may contribute to an elevation
      of blood pressure in Wistar fatty rat with hyperglycemia and hyperinsulinemia.
      This salt sensitivity may change the abnormal pressure-natriuresis responses.

PMID- 8743541
TI  - Mechanical force regulation of vascular parathyroid hormone-related peptide
      expression.
AB  - Parathyroid hormone-related peptide (PTHrP) was originally identified as a factor
      responsible for the syndrome of humoral hypercalcemia of malignancy. PTHrP has a
      vasodilator activity and is produced in vascular smooth muscle. However, the
      exact physiological role of PTHrP and the regulation of its gene expression in
      the vascular system have not been understood. We found that the mechanical
      stretch of rat aortic smooth muscle cells in vitro induced a marked increase in
      PTHrP expression through a protein kinase C-dependent mechanism. We further
      examined whether PTHrP expression in blood vessels in vivo is regulated by
      mechanical forces. Mechanical stretch of isolated aortic strips increased the
      expression of PTHrP mRNA. The PTHrP mRNA expression levels in aortae from
      hypertensive 18-week-old spontaneously hypertensive rats (SHR) was twofold higher
      than age-matched control Wistar-Kyoto (WKY) rats, while the PTHrP mRNA level in
      the aortae from normotensive 4-week-old SHR was not different from that of age
      matched control WKY rats. Moreover, treatment of hypertensive SHR with an
      angiotensin II type 1 receptor antagonist or hydralazine caused a decrease in
      PTHrP expression in the aortae with the lowering of blood pressure. These results
      indicate that the gene expression of the vasoleraxant PTHrP in blood vessels is
      under the regulation of mechanical forces, and suggest a modulatory role for
      PTHrP in the regulation of vascular tone.

PMID- 8743542
TI  - Interaction of 11 beta-hydroxysteroid-oxido reductase in different organs of
      various mammalian species.
AB  - Distribution of 11 beta-HSOR activity in different organs has been measured using
      tissue slices, homogenates, and microsomes. The biological material was incubated
      in vitro with cortisol/ cortisone (human preparations) or corticosterone/11
      dehydrocorticosterone, respectively (animal preparations). Metabolites formed
      were quantified using RP-HPLC and on-line detection of labeled compounds. The
      typical pattern of CS-metabolism as obtained with rat tissue slices revealed that
      testis, rectum and kidney are predominant oxidizers of active gluco-CS, while
      liver and lung mainly function as reducers. Human placenta preparations display
      an exclusive oxidase activity. To trace different types of 11 beta-HSOR
      homogenates and microsomes of various organs were incubated with different
      cosubstrates (NAD+/NADH or NADP+/ NADPH, respectively). In accordance with
      previous reports, this study found that isoenzymes with different cosubstrate
      preferences exist in individual organs. 11 beta-HS oxidase activity displays a
      NAD+ preference in the human placenta. There was no apparent difference in
      cosubstrate preference between human and guinea pig placenta homogenates. In mice
      there is also a detectable reductive activity, whereas the Sprague-Dawley rat and
      golden hamster do not show any detectable activities.

PMID- 8743543
TI  - Risk factors for left ventricular hypertrophy: role of Na(+)-Li+
      countertransport.
AB  - Left ventricular hypertrophy (LVH) is associated with an increase in
      cardiovascular death in essential hypertension (EH). The factors involved in LVH
      are multiple and complex. We looked for risk factors of LVH in a group of 28
      nonobese patients with EH (mean age = 45.3 years). We analyzed the activity of
      several erythrocyte ion transports (Vmax of NaLi countertransport, NaKCl
      cotransport and NaK-pump, and the Na-leak Kp Na), the intracellular Na and the
      insulin sensitivity index. All these parameters were used as independent
      variables whereas the left ventricular mass index (LVMI) was used as the
      dependent variable. Variables showing a significant univariate correlation (age,
      time of EH, mean blood pressure and Vmax of NaLi countertransport) were
      introduced in a stepwise multiple regression model. Only age (P = 0.014), time of
      EH (P = 0.038) and Vmax of NaLi countertransport (P = 0.032) were independently
      associated with LVMI (R2 = 0.581, P = 0.0001). The NaLi CT, an operating mode of
      the NaH exchanger that facilitates cellular growth, may be a marker of LVH, and
      consequently a marker of increased cardiovascular risk.

PMID- 8743544
TI  - A transient role of the kidney in the maintenance of hypertension.
AB  - Using the Prague hypertensive rat (PHR), a model derived from the Wistar rat, in
      which a normotensive parallel, the Prague normotensive rat (PNR), was bred from
      the same parent pair (so that transplantation of organs between both these
      parallel rat model lines results in no distinct signs of rejection), we were able
      to show that hypertension travels with the kidney. Transplantation of a kidney
      from PHR to a bilaterally nephrectomized (BNX) PNR led to an increase in systolic
      blood pressure (SBP) in the recipient for 10 weeks after grafting. Similarly, a
      decrease in SBP was seen in BNX PHR for the same period of time after grafting a
      kidney from PNR. If, however, the SBP was measured over a longer period of time,
      because the elevated SBP slowly drops after grafting a kidney from PHR to BNX
      PNR, it is less than 130 mm Hg in the fourth month and thereafter. If BNX PHR
      receives a kidney from PNR, the decrease in SBP is permanent, amounting to 126.3
      +/- 12.7 mm Hg one year after transplantation. The grafting of a heart from PHR
      to the abdominal aorta of PNR does not influence SBP. In conclusion, the presence
      of a kidney from PHR is necessary for the development, but is not sufficient for
      the maintenance of hypertension. The heart of PHR is not "hypertensogenic" as is
      the kidney.

PMID- 8743545
TI  - Renal abnormality of calcium handling in spontaneously hypertensive rats.
AB  - Hypercalciuria has been observed in human and experimental hypertension. The
      distal convoluted tubule (DCT) is the site of fine regulation for Ca2+ excretion.
      We assessed the cellular factors responsible for Ca2+ reabsorption in the DCT of
      spontaneously hypertensive rats (SHR). Vitamin D3 dependent Ca-binding protein
      28k (CaBP28k), a factor involved in Ca2+ influx, and plasma membrane Ca ATPases
      (PMCA), a factor involved in Ca2+ efflux, were studied in hypertensive 16-week
      old SHR and normotensive Wistar-Kyoto rats (WKY). mRNA levels for CaBP28k, PMCA 2
      and PMCA 4 were not different in the two strains. However, CaBP28k protein was
      more abundant, and PMCA protein was less abundant in SHR than in WKY. PMCA
      antibody recognized only DCT in the two strains. In conclusion, decreased PMCA in
      DCT may be responsible for the hypercalciuria in SHR.

PMID- 8743546
TI  - Hypertensive glomerular damage as revealed by the expression of alpha-smooth
      muscle actin and non-muscle myosin.
AB  - The aim of this study was to determine the phenotypic modulation in mesangial
      cells of glomeruli damaged by hypertension. Salt-loaded stroke-prone
      spontaneously hypertensive rats were untreated or treated with a calcium
      antagonist, manidipine (2 mg/kg/day) for eight weeks. In normotensive Wistar
      Kyoto rats, alpha-smooth muscle actin was not expressed in any glomerular cells
      and a non-muscle myosin heavy chain isoform, SMemb, was slightly expressed in
      glomerular visceral epithelial cells. In the untreated hypertensive rats, the
      glomeruli showed sclerosis to various degrees and expressed alpha-smooth muscle
      actin and SMemb. Normal expression of SMemb in the epithelial cells disappeared.
      Notably, alpha-smooth muscle actin-positive fibroblast-like cells appeared in the
      interstitium, especially around the Bowman's capsules. Manidipine ameliorated the
      glomerulosclerosis and reduced the expression of alpha-smooth muscle actin in
      mesangial cells. In conclusion, the mesangial cells changed their phenotypes and
      expressed alpha-smooth muscle actin and SMemb in the glomeruli during the
      development of hypertensive renal damage. These phenotypically changed mesangial
      cells are considered to be activated and to produce various kinds of cytokines
      and extracellular matrix, which leads to glomerulosclerosis. Manidipine
      attenuated the glomerular damage and the phenotypic changes. The functional
      relevance of phenotypic changes in these cells should be elucidated in future
      studies.

PMID- 8743547
TI  - Is hypertension a mortality risk factor in dialysis?
AB  - We retrospectively studied 370 chronic uremic patients, 234 males and 136 females
      with a mean age of 53 +/- 15 years, to determine the number of mortalities due to
      hypertension. With hypertension defined as blood pressure values > 150/90, a
      total of 168 patients were found to be normotensive and 202 as hypertensive.
      Blood pressure was also considered in association with some prognostic variables
      such as the patient's age, time of dialysis, renal diagnosis, and dialytic
      treatment (hemodialysis or peritoneal dialysis). No significant difference in
      survival was found between normotensive and hypertensive patients. Patients with
      diabetic nephopathy had a significantly poorer survival experience with respect
      to other nephropathies, independently of blood pressure values after beginning
      dialysis treatment. The Cox proportional hazard analysis showed an increased risk
      of death from aging and peritoneal dialysis, while the chi 2 test showed the role
      of hypertension as a mortality risk factor only in patients less than 50 years
      old (18% of deaths among normotensives vs. 31% of deaths among hypertensives, P <
      0.05). We conclude that hypertension does not seem to represent the primary risk
      factor for overall survival in dialysis therapy.

PMID- 8743548
TI  - Nocturnal blood pressure elevation in transplanted pediatric patients.
AB  - Ambulatory blood pressure monitoring during 24 hours was applied in 34 pediatric
      patients aged 6.3 to 24.3 (median 14.0) years who had been transplanted 0.3 to
      8.4 years previously. The mean arterial blood pressure levels measured during the
      daytime and at night correlated positively (r = 0.70), but 14 of the 28 patients
      with nocturnal hypertension were normotensive during the day. A reduced nocturnal
      dip (< 5.5%) of mean arterial blood pressure was detected in 11 of 34 patients.
      In the first year post-transplantation 4 of 7 patients had an attenuated dip
      without any obvious cause. Beyond the first year a reduced dip was always
      associated with a renal pathology. In conclusion, a high prevalence of nocturnal
      hypertension was detected in grafted pediatric patients, even in presence of
      normal daytime blood pressures. An attenuated nocturnal dip was found in
      association with an underlying renal pathology or within the first post
      transplant year.

PMID- 8743549
TI  - Functional characterization of vasopressin V1 and V2 receptors in the rabbit
      renal cortical collecting duct.
AB  - Recently we clarified the mechanism in which arginine-vasopressin (AVP) applied
      from the luminal side inhibits the basolateral Cl- conductance, which is
      stimulated by basolateral AVP. However, to prove that these vasopressin phenomena
      are expressed via receptor mediated actions, we examined the effect of specific
      V1 and V2 receptor antagonists, OPC-21268 and OPC-31260, respectively, on the
      electrical response to vasopressin in the rabbit CCD perfused in vitro. In the
      presence of the V2-antagonist, basolateral AVP caused only the activation of
      luminal Na+ conductance, indicating a V1 action. In the presence of the V1
      antagonist, basolateral AVP caused the same biphasic responses in electrical
      parameters as cyclic AMP, representing a pure V2 action. On the other hand, a
      rise in cell Ca2+ in response to AVP was completely abolished in the presence of
      the V1-antagonist, but not by the V2-antagonist in the bath. These data confirm
      our earlier findings that rabbit CCD possesses both V1 and V2 receptors in the
      basolateral membrane. We conclude that electrical responses to AVP in the rabbit
      CCD are a complex of V1 and V2 receptor-mediated actions.

PMID- 8743550
TI  - Functional analysis and chromosomal gene assignment of rat kidney prostaglandin
      EP3 receptor.
AB  - We have reported two isoformes of rat prostaglandin EP3 receptor with their
      different carboxyl-terminal tails (rEP3A and rEP3B receptors), which are derived
      by alternative RNA splicing, and both receptors have been shown to be localized
      to renal distal tubules. In the present study, we characterized the signal
      transduction system of rat kidney EP3 receptors either in a renal cell line
      mimicking renal distal tubule cells, TKC2, or in COS-7 cells by functional
      expression of these receptors. We also examined the chromosomal localization of
      the EP3 receptor gene by fluorescence in situ hybridization (FISH). In TKC2
      cells, vasopressin (AVP, 10(-7) M), prostaglandin (PG) E2 (10(-7) M), or
      forskolin (10(-8) M) markedly stimulated cyclic AMP formation. Overexpression of
      the rEP3A receptor significantly attenuated the AVP-, PGE2- or forskolin-induced
      cyclic AMP formation, whereas there was no change with rEP3B receptor expression.
      On the other hand, in COS-7 cells transfected with rEP3A receptor cDNA, PGE2 (10(
      7) M) did not affect cytosolic free calcium concentration ([Ca2+]i), whereas
      transfection of rEP3B receptor cDNA evoked PGE2-induced increases in [Ca2+]i.
      Moreover, we have revealed that the rEP3 receptor gene is localized to rat
      chromosome 2q44-45. In conclusion, rEP3A or rEP3B receptor is suggested as a
      mediator of the natriuretic/diuretic action of PGE2 in renal distal tubules via a
      decrease in cyclic AMP formation or an increase in [Ca2+]i, respectively.
      Information of the gene assignment of rat EP3 receptor to rat chromosome 2q44-45
      is useful for further analysis of the role of EP3 receptor in genetically
      hypertensive rat models.

PMID- 8743551
TI  - Initiating requests during community-based vocational training by students with
      mental retardation and sensory impairments.
AB  - Students with mental retardation and deafness or deaf-blindness often need some
      type of communication system to communicate effectively with communication
      partners during community-based vocational training. However, students may need
      specific training to learn how to initiate requests for items or assistance, a
      skill identified as critical for job success. Students were taught to initiate
      requests using dual communication boards and gestures. Data were recorded on
      student performance using a multiple-baseline probe design in which data were
      collected during baseline, intervention, and generalization phases. Students were
      able to initiate requests with 80% to 100% accuracy with the communication system
      at vocational sites. Training students to initiate requests may need to be
      targeted when students are first learning a job, as this is when most naturally
      occurring opportunities exist.

PMID- 8743552
TI  - Basic money-counting skills of children with mental retardation.
AB  - The thought processes involved in counting and comparing small amounts of money
      among children and adolescents with Down syndrome (n = 17), other children and
      adolescents with mental retardation of unknown etiologies (n = 17), and normally
      developing first graders (n = 15) were examined. Three different tasks that
      progressively reduced the cognitive demands placed on the children were used.
      Although not generally different from each other, the two groups of children with
      mental retardation had far greater difficulties with the tasks than normals.
      Also, as the complexity of the counting task increased, the number of comparison
      errors made by the children with mental retardation increased. Based on the
      findings, a program for teaching money principles to children with mental
      retardation was proposed.

PMID- 8743553
TI  - Component analysis and stimulus control assessment of a behavior deceleration
      treatment package.
AB  - A treatment package that included two setting condition manipulations and visual
      occlusion was implemented to gain control over the high-intensity screaming and
      whining of a 16-year-old female with developmental disabilities. The study
      included an analysis of the individual and combined components of the treatment
      package and a stimulus control analysis of three salient features of the visual
      occlusion apparatus (i.e., opaque screen, secured helmet, and cranial pressure).
      Results showed that the treatment package occasioned a deceleration in the two
      targeted vocal behaviors and a reduction in the amount of time the participant
      was required to wear the occlusion apparatus. An analysis of the apparatus
      suggested that the critical element needed to control inappropriate vocalizations
      appeared to be cranial pressure, which was naturally produced by the helmet.
      Consequently, the helmet was eliminated and cranial pressure was produced by a
      woman's headband. Follow-up data, collected 1, 2, and 3 months after termination
      of systematic intervention, revealed near-zero levels of screaming and whining
      behaviors. A 9-month follow-up investigation involving the removal and subsequent
      reinstatement of the headband procedure supported the use of the headband for the
      maintenance of behavioral gains.

PMID- 8743554
TI  - Social information processing in mild mentally retarded children.
AB  - This study examined the social information processing (SIP) skills of mild
      mentally retarded (MR) children using Dodge's model. Six sets of pictures
      depicting provocation situations were used to elicit measures of accuracy of
      interpretation to accidental and hostile cues, attribution of ambiguous cues, and
      hostile and nonhostile behavior responses to all three types of cues. MR children
      were compared to nonretarded groups matched for chronological age (CA-matched)
      and mental age (MA-matched) on these variables. Compared to both nonretarded
      groups, the MR group was less accurate in interpretation of accidental cues and
      more hostile in their responses to the ambiguous cues. The latter finding
      remained even after partialing out externalizing behavior problems. The results
      are discussed in terms of factors associated with SIP skills, and the assessment
      and treatment of MR children.

PMID- 8743556
TI  - Emerging multipotent aspects of hepatocyte growth factor.
AB  - Specific tissue interactions between epithelia and mesenchyme (or stroma), e.g.,
      epithelial-mesenchymal (or -stromal) interactions mediate crucial aspects of
      normal development and tissue regeneration. These events affect tissue induction,
      organogenesis, cell movement, and morphogenesis of multicellular structures.
      Extensive and diverse studies have established that hepatocyte growth factor
      (HGF), a ligand for the c-met protooncogene product of receptor tyrosine kinase,
      is a mesenchymal- or stromal-derived multipotent polypeptide which mediates
      epithelial-mesenchymal interactions. During embryogenesis, HGF supports
      organogenesis and morphogenesis of various tissues and organs, including the
      liver, kidney, lung, gut, mammary gland, tooth, skeletal system, etc. In adult
      tissues, HGF elicits a potent organotrophic function which supports regeneration
      of organs including the liver, kidney, and lung. In the brain, HGF is a new
      member of the family of neurotrophic factors. In neoplastic tissue, HGF is
      involved in tumor invasion and metastasis, through tumor-stromal interactions.
      While HGF was originally identified as a potent mitogen for mature hepatocytes,
      the biological functions of this factor reach far beyond the original
      identifications. Such being the case, use of HGF for purposes of therapeutics is
      being given increasing attention.

PMID- 8743555
TI  - Some current themes in functional analysis research.
AB  - The purpose of this article is to review and discuss some current themes in
      functional analysis research. The paper is divided into two general sections; one
      section discusses clinical application of functional analysis and a second
      section discusses functional analysis as a research method. In the first section,
      current issues related to treatment logic and development are reviewed. Also,
      clinical limitations of functional analysis are described, including treatment
      and assessment implementation issues (such as time and resource constraints). In
      the second section, three areas of research are reviewed with suggestions for
      further research: the analysis of diverse response topographies, the analysis of
      basic behavioral processes, and the evaluation of methodological refinements.

PMID- 8743557
TI  - Truncation of Vargula luciferase still results in retention of luminescence.
AB  - Significant amino acid sequence homology in two regions of Vargula hilgendorfii
      to one in apoaequorin was reported. The intra-amino acid homology in Vargula
      luciferase between residues 81-312 and 321-540 was 19.3%, and each of this intra
      homologous region contained the region homologous to apoaequorin. In order to
      prove the possibility that only one of the homologous regions is sufficient for
      luminescence, we have produced a chimeric protein comprising of only the N
      terminal homologous region of Vargula luciferase fused to protein A. Comparison
      of the luminescence of this truncate luciferase indicated that there was 38.5%
      retention in the bioluminescence of luciferase when compared to that of the
      mature form of luciferase. This fact may have interesting implications for
      further study of engineering luciferase.

PMID- 8743558
TI  - A 31-kDa recombinant fibronectin cell-binding domain fragment: its binding to
      receptor, cell adhesive activity, and fusion proteins.
AB  - The binding of fibronectin to fibronectin receptor was studied using a
      recombinant 31-kDa cell-binding domain fragment of fibronectin (C279), which
      consisted of three type III repeats (III8-III9-III10). Fibronectin receptor in
      several cell lysates was bound to a column of C279-immobilized Sepharose HP and
      obtained in a highly purified form by elution with a synthetic peptide, GRGDSP.
      alpha 5 beta 1-Integrin was detected in the GRGDSP-eluted fraction by
      immunoblotting. The cell-adhesive activity of C279 was inhibited by GRGDSP
      peptide, an anti-integrin a5 subunit antibody, and an anti-integrin beta 1
      subunit antibody. The cell adhesion of fusion proteins of the 31-kDa fragment
      with biologically interesting polypeptides (heparin-binding domain of
      fibronectin, and basic fibroblast growth factor) was also studied. In the
      presence of an anti-integrin a5 subunit antibody, human fibrosarcoma HT-1080
      cells attached to the fusion protein containing fibroblast growth factor, giving
      rise to changes the morphology of the attached cells. The cell adhesion of C279
      was inhibited by GRGDSP peptide but that of the fusion protein with the heparin
      binding domain of fibronectin was not completely inhibited by the peptide. These
      results suggest that these biologically interesting polypeptides contribute to
      the cell adhesion of the fusion proteins.

PMID- 8743559
TI  - Coconut oil affects lipoprotein composition and structure of neonatal chicks.
AB  - Supplementation of 10 or 20% coconut oil in the diet for 1-2 weeks produced a
      significant hypercholesterolemia in neonatal chicks. Plasma triacylglycerol
      concentration significantly increased after the addition of 20% coconut oil for 2
      weeks. These results show that newborn chicks are more sensitive to saturated
      fatty acids from coconut oil than adult animals. The effects of this saturated
      fat on lipoprotein composition were studied for the first 1-2 weeks of neonatal
      chick life. Coconut oil supplementation in the diet (20%) for 2 weeks increased
      cholesterol concentration in all the lipoprotein fractions, while 10% coconut oil
      only increased cholesterol in low-density and very-low-density lipoproteins, an
      increase that was significant after 1 week of treatment. Similar results were
      obtained for triacylglycerol concentration after 2 weeks of treatment. Changes in
      phospholipid and total protein levels were less profound. Coconut oil decreased
      low-density and very-low-density lipoprotein fluidity, measured as total
      cholesterol/phospholipid ratio. Changes in esterified cholesterol/phospholipid
      and triacylglycerol/phospholipid ratios suggest that coconut oil affects the
      distribution of lipid components in the core of very-low-density particles.
      Likewise, the esterified cholesterol/triacylglycerol ratio was clearly increased
      in the low-density, and especially in the very-low-density, fraction after the
      first week of coconut oil feeding. Our results show that neonatal chick provides
      a suitable model in which to study the role of very-low-density lipoproteins in
      atherogenesis and the rapid response to saturated fatty acids with 12-14 carbons.

PMID- 8743560
TI  - Microsomal aldehyde oxygenase (MALDO): purification and characterization of a
      cytochrome P450 isozyme responsible for oxidation of 9-anthraldehyde to 9
      anthracenecarboxylic acid in monkey liver.
AB  - Oxidative activity of 9-anthraldehyde (9-AA) to 9-anthracenecarboxylic acid in
      monkey liver was mainly located in microsomes. The reaction required NADPH as an
      essential cofactor and was significantly inhibited by SKF 525-A, metyrapone,
      disulfiram, and CO, potent inhibitors of microsomal aldehyde oxygenase (MALDO).
      Two cytochrome P450 isozymes, named P450JM-A and P450JM-C, which mediate the
      oxidative biotransformation of 9-AA were purified from hepatic microsomes of
      untreated male and female Japanese monkeys, respectively. These isozymes each
      showed a single band of molecular mass 51,000 on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The NH2-terminal amino acid sequences of
      P450JM-A and P450JM-C are highly homologous with those of several P450s belonging
      to the CYP2A and CYP2B subfamilies, respectively. The anti-P450JM-C antibody
      significantly suppressed 9-AA MALDO activity in monkey liver, but anti-P450JM-A
      antibody did not. The antibody against CYP2C11, which is a major isozyme
      responsible for 9-AA MALDO in male rat liver, also inhibited the activity. These
      results indicate that P450JM-C and isozyme(s) immunologically related to CYP2C11
      predominantly possess MALDO activity toward 9-AA.

PMID- 8743561
TI  - Phosphorylated sites of M(r) 25,000 protein, a putative protein phosphatase 2A
      modulator, and phosphorylation of the synthetic peptide containing these sites by
      protein kinase C.
AB  - The M(r) 25,000 protein isolated from Xenopus laevis oocytes was shown to be an
      effective phosphate acceptor for Ca(2+)-phospholipid-dependent protein kinase
      (protein kinase C) [Hashimoto, E. et al. (1995) J. Biochem. 118, 453-460]. In
      this study, the sites of this protein phosphorylated by protein kinase C were
      determined and the mechanism of substrate recognition was studied using a
      synthetic peptide containing the phosphorylation sites. After incorporation of
      about 2 mol of phosphate per mol of this protein, the radioactive protein was
      digested with trypsin and the phosphopeptides were purified by a series of column
      chromatographies. The amino acid sequence of the major radioactive peptide was
      shown to be Ser-Arg-Val-Ser-Lys-Arg. This and previous results suggest that the
      two serine residues at the amino-terminal region were phosphorylated by protein
      kinase C. To confirm this, the phosphorylated protein was directly analyzed for
      the amino acid sequence. The percent distribution of dithiothreitol adduct of the
      phenylthiohydantoin derivative of serine (PTH-serine) compared with that of PTH
      serine increased at the first and fourth cycles of the sequence analysis. When
      the synthetic peptide composed of the amino-terminal eleven amino acids was
      employed as phosphate acceptor, the Km value was unexpectedly high (1.1 mM)
      compared with that of the native protein (0.5 muM). A stimulatory effect of M(r)
      25,000 protein on the activity of protein phosphatase 2A was further enhanced
      after phosphorylation by protein kinase C. These results suggest that the two
      serine residues recognized by protein kinase C may have some role in the
      regulation of this M(r) 25,000 protein.

PMID- 8743562
TI  - Purification and characterization of novel trypsin-like serine proteases from
      mouse spleen.
AB  - Novel trypsin-like serine proteases (mouse trypsin-type serine proteases 1 and 2
      [MTSP-1 and -2]) were purified to homogeneity from mouse spleen. Each protease
      consisted of a single polypeptide with a molecular mass of about 29 kDa, as
      determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis under
      reducing conditions. Both were totally inhibited by diisopropylfluorophosphate,
      soybean trypsin inhibitor, aprotinin, antipain, and leupeptin and partially
      inhibited by chymostatin and dithiothreitol, suggesting that they are trypsin
      like serine proteases. They hydrolyzed synthetic substrates for trypsin-like
      proteases but not those for chymotrypsin-like proteases, elastase and kallikrein.
      MTSP-1 hydrolyzed tert-butyloxycarbonyl (Boc)-Asp(OBzl)Pro-Arg-amino-4-methyl
      coumaryl-7-amide (MCA) and Boc-Ile-Glu-Gly-Arg-MCA faster than Boc-Phe-Ser-Arg
      MCA. On the other hand, MTSP-2 hydrolyzed Boc-Phe-Ser-Arg-MCA most rapidly, with
      a specific activity 15 times higher than that of MTSP-1. The N-terminal amino
      acid sequence of MTSP-1 was Ile-Val-Gly-Gly-Tyr-Thr-His-Leu-Asp-Asn-Gln-Val-Pro
      Tyr. This sequence was 71% homologous with the N-terminal of bovine trypsin. The
      Boc-Phe-Ser-Arg-MCA hydrolyzing activity of mouse spleen significantly (p < 0.01)
      increased to about 1.5-fold the basal activity 2 weeks after an injection of
      Freund's complete adjuvant, suggesting that these proteases are involved in the
      immune response.

PMID- 8743563
TI  - Binding of anti-band 3 autoantibody to sialylated poly-N-acetyllactosaminyl sugar
      chains of band 3 glycoprotein on polyvinylidene difluoride membrane and sepharose
      gel: further evidence for anti-band 3 autoantibody binding to the sugar chains of
      oxidized and senescent erythrocytes.
AB  - Binding specifically of naturally occurring anti-band 3 IgG antibody isolated
      from human plasma was investigated in a cell-free binding system. 125I-labeled
      human anti-band 3 IgG specifically bound to band 3 glycoprotein and lactoferrin,
      a glycoprotein that has poly-N-acetyllactosamine-type sugar chains like band 3,
      on the polyvinylidene difluoride blotting membrane. Binding was decreased by 50
      70% when band 3 and lactoferrin were pretreated with N-glycosidase F, endo-beta
      galactosidase, or neuraminidase. Binding of 125I-anti-band 3 IgG to band 3
      Sepharose gel was partially inhibited by band 3 oligosaccharides or lactoferrin,
      but was less inhibited by them after they had been treated with N-glycosidase F
      or endo-beta-galactosidase. A significant part of 125I-anti-band 3 IgG that bound
      to the band 3-Sepharose gel was released upon treatment of the gel with N
      glycosidase F or endo-beta-galactosidase. IgG that binds to lactoferrin (anti
      lactoferrin IgG) was isolated from normal human plasma. 125I-Anti-lactoferrin IgG
      bound to the band 3-Sepharose gel as effectively as to the lactoferrin-Sepharose.
      The antibody specifically bound to the band 3- and lactoferrin-blotted membrane
      depending on the poly-N-acetyllactosaminyl sugar chains of the blotted
      glycoproteins. The results indicate that a major part (about 70%) of anti-band 3
      IgG recognizes the sialylated poly-N-acetyllactosaminyl sugar chains of band 3
      and lactoferrin, and the remaining part (about 30%) of the antibody may recognize
      the polypeptide portion of band 3. This was supported by the observation that
      anti-band 3 IgG effectively bound to lactoferrin-Sepharose but 33% of the
      antibody did not. Anti-band 3 IgG with the carbohydrate-binding property was
      equally obtained whether fully denatured or barely denatured band 3 was used for
      isolation of anti-band 3 IgG by affinity chromatography. These results provide
      further evidence for our proposal that the binding sites of anti-band 3 IgG to
      oxidized and senescent erythrocytes reside on the locally condensed sialylated
      poly-N-acetyllactosaminyl sugar chains of band 3 on the cell surface.

PMID- 8743564
TI  - Purification and catalytic properties of a novel acetohexamide-reducing enzyme
      from rabbit heart.
AB  - An enzyme catalyzing the metabolic reduction of acetohexamide [4-acetyl-N
      (cyclohexyl-carbamoyl)benzenesulfonamide], an oral antidiabetic drug, was
      purified to homogeneity from the cytosolic fraction of rabbit heart. The
      molecular mass of the purified enzyme was estimated to be 110 kDa by gel
      filtration and nondenaturing PAGE and 28 kDa by SDS-PAGE, suggesting that the
      enzyme is composed of four identical-size subunits. 4-Benzoyl-pyridine and p
      nitroacetophenone, typical substrates of carbonyl reductase [EC 1.1.1.184], were
      not reduced by the enzyme. Of drugs with a ketone group tested, only
      acetohexamide was a good substrate of the enzyme. the enzyme effectively reduced
      analogs substituted with various alkyl groups instead of the cyclohexyl group in
      acetohexamide, although it had little or no ability to reduce analogs substituted
      with various alkyl groups instead of the methyl group in acetohexamide. The
      enzyme was inhibited not only by quercetin, a well-known inhibitor of carbonyl
      reductase, but also by phenobarbital, a potent inhibitor of aldehyde reductase
      [EC 1.1.1.2]. These results indicate that the enzyme purified from rabbit heart
      is a novel enzyme responsible for the reduction of acetohexamide and its analogs.

PMID- 8743565
TI  - Characterization and comparison of synthetic immobile and mobile Holliday
      junctions.
AB  - Eight synthetic Holliday junction (HJ) oligonucleotides containing an immobile or
      a mobile junction were characterized by gel electrophoresis, ultraviolet
      absorption and circular dichroism (CD) spectroscopy. Four 24-mer
      deoxyribonucleotides formed stable immobile and mobile HJs in 0.1 M NaCl at 5 muM
      strand concentration at room temperature. However, the immobile HJ constructed
      from four 18-mers was less stable, and four 12-mers did not form the HJ structure
      under the conditions used. A comparison of the melting profiles of the HJs with
      those of the duplexes corresponding to the arms of four-way junctions indicated
      that the thermal stability of the HJ was similar to that of the individual arm
      and the cooperativity of the melting behavior of the HJ was relatively higher
      than that of the individual arm duplex. The Tms of the mobile HJs containing 4,
      6, 8, and 10 base-pair homologous cores at junctions were essentially identical
      with that of the immobile HJ of the same size. There is a tendency that the HJ
      containing a larger homologous core region becomes more resistant to thermal
      denaturation. The addition of divalent metal cations, Mg2+ and Ca2+, to the
      solutions of the HJs raised their melting temperatures. The difference found for
      the CD spectra of the HJs which differ only in the arrangement of the HJ depended
      primarily upon the DNA sequence flanking the junction. The RuvC protein binds to
      the immobile and mobile HJs, regardless of the presence and the size of the
      homologous core at the junction.

PMID- 8743566
TI  - Characterization of chitin synthase 2 of Saccharomyces cerevisiae. II: Both full
      size and processed enzymes are active for chitin synthesis.
AB  - When chitin synthase 2 of Saccharomyces cerevisiae was overexpressed in yeast
      cells using GAL1 promoter, deletion of the N-terminal 193 amino acids
      significantly increased the level of the protein without affecting its
      characteristics. We partially purified N-terminally truncated chitin synthase 2
      by product entrapment and ion exchange column chromatography, and found that it
      was active even without trypsin treatment when appropriate divalent cations were
      present in the reaction mixture. This chitin synthase activity was independent of
      the N-terminal 193 amino acid truncation, because partially purified full length
      enzyme also exhibited the activity without trypsin treatment in the presence of
      appropriate cations. Furthermore, the molecular weights of these two forms of
      chitin synthase 2 were coincident with those estimated from the deduced amino
      acid sequence, and most of the chitin synthase 2 in the yeast membrane was
      present as an unprocessed form, as judged from its molecular weight. Treatment of
      either full length or truncated enzyme with trypsin, however, further increased
      the enzyme activity by four to fivefold, and produced a 35 kDa polypeptide that
      specifically reacted with monoclonal antibody raised against the region
      containing the putative active site of chitin synthase 2. Thus, it appears that
      predominant native (unprocessed) chitin synthase 2 is active, but the 35 kDa
      region encompassing the active site is sufficient for the catalytic activity.

PMID- 8743567
TI  - Purification and refolding of recombinant human proMMP-7 (pro-matrilysin)
      expressed in Escherichia coli and its characterization.
AB  - Human matrix metalloproteinase-7 (MMP-7 = matrilysin) was overproduced in
      Escherichia coli as a recombinant zymogen (31 kDa), the C-terminus of which bears
      artificial hexa-histidines. Most of the enzyme was isolated from the insoluble
      fraction of the cell lysate and purified by a single step using Ni-NTA resin
      after solubilization of the precipitates with 8 M urea solution. The resin-bound
      recombinant protein was refolded into a form that is activatable by p-amino
      phenylmercuric acetate in an autocatalytic manner. The activated enzyme cleaved a
      synthetic peptide substrate at the reported site for MMP-7. Digestion of
      carboxymethylated transferrin (a natural substrate of MMP-7) by the recombinant
      proteinase generated fragments with the same peptide map as in the case of native
      purified MMP-7. The autocatalytic activation and enzyme reaction were entirely
      dependent on the presence of calcium and zinc ions. The enzyme activity to cleave
      carboxymethylated transferrin was inhibited by tissue inhibitors of
      metalloproteinases-1 and -2, MMP-specific inhibitors. The activity of the
      recombinant MMP-7 was also inhibited by a synthetic peptide derived from a part
      of the cysteine switch that maintains the zymogen in an inactive state. Thus, we
      report here a simple means of preparing a large quantity of recombinant proMMP-7
      that can be used to study the activation mechanism and to screen synthetic
      inhibitors.

PMID- 8743568
TI  - Acid-induced folding of yeast alcohol dehydrogenase under low pH conditions.
AB  - Under conditions of low pH, the conformational states of holo-YADH and apo-YADH
      were examined by protein intrinsic fluorescence, ANS fluorescence, and far-UV CD
      measurements. The results obtained show that a low ionic strength, with the
      addition of HCl, the holo- and apo- YADH denatured gradually to reach the
      ultimate unfolded conformation in the vicinity of pH 2.0 and 2.5, respectively.
      With the decrease of pH from 7.0 to 2.0, the fluorescence emission decreased
      markedly, with its emission maximum red-shifting from 335 to 355 nm, indicating
      complete exposure of the buried tryptophan residues to the solvent. The far-UV CD
      spectra show the loss of the arrayed secondary structure, though the acid
      denatured enzyme still maintained a partially arrayed secondary structure. A
      further decrease in pH by increasing the concentration of HClO4 induced a
      cooperative folding of the denatured enzyme to a compact conformation with the
      properties of a molten globule, described previously by Goto et al. [Proc. Natl.
      Acad. Sci. USA 87, 573-577 (1990)]. More extensive studies showed that although
      apo-YADH and holo-YADH exhibited similar behavior, the folding cooperative
      ability of apo-YADH was lower than that of the holo-enzyme. From the above
      results, it is suggested that the zinc ion plays an important role in the proper
      folding of YADH and in stabilizing its native conformation.

PMID- 8743569
TI  - Lysyl-tRNA synthetase from Bacillus stearothermophilus. Purification, and
      fluorometric and kinetic analysis of the binding of substrates, L-lysine and ATP.
AB  - Lysyl-tRNA synthetase [L-lysine:tRNA(Lys)ligase (AMP forming); EC 6.1.1.6] was
      purified from Bacillus stearothermophilus NCA1503 approximately 1,100-fold to
      homogeneity in PAGE. The enzyme is a homodimer of M(r) 57,700 x 2. The molar
      absorption coefficient, epsilon, at 280 nm is 71,600 M-1.cm-1 at pH8.0. Enzyme
      activity in the tRNA aminoacylation reaction and the ATP-PPi exchange reaction
      increases up to 50 degrees C at pH 8.0, but is lost completely at 70 degrees C.
      The pH-optima of the two reactions are 8.3 at 37 degrees C. In the tRNA
      aminoacylation reaction, the Km values for L-lysine and ATP are 16.4 and 23.2
      muM, respectively, and in the ATP-PPi exchange reaction, the Km values for L
      lysine and ATP are 23.6 and 65.1 muM, respectively at 37 degrees C, pH 8.0.
      Interaction of either L-lysine or ATP with the enzyme has been investigated by
      using as a probe the ligand-induced quenching of protein fluorescence and by
      equilibrium dialysis. These static analyses, as well as the kinetic analysis of
      the L-lysine dependent ATP-PPi exchange reaction indicate that the binding mode
      of L-lysine and ATP to the enzyme is sequential ordered (L-lysine first). The
      interaction of lysine analogues with the enzyme has also been investigated.

PMID- 8743570
TI  - A novel phenylserine dehydratase from Pseudomonas pickettii PS22: purification,
      characterization, and sequence of its phosphopyridoxyl peptide.
AB  - A novel phenylserine dehydratase [EC 4.2.1.-], which catalyzes the deamination of
      L-threo-3-phenylserine to yield phenylpyruvate and ammonia, was purified to
      homogeneity from a crude extract of Pseudomonas pickettii PS22 isolated from
      soil. The enzyme was a monomer having a molecular mass of about 38 kDa and
      contained 1 mol of pyridoxal 5'-phosphate per mol of enzyme. The enzyme exhibited
      absorption maxima at 279 and 416 nm. No appreciable spectral change was observed
      over the pH range of 6.0 to 8.0. The maximal reactivity was obtained at about pH
      7.5. The enzyme was highly specific for L-threo-3-phenylserine (Km, 0.21 mM). L
      erythro-3-Phenylserine, L-threonine, L-serine, and D-serine were inert. The
      enzyme was inhibited by phenylhydrazine, hydroxylamine, p-chloromercuribenzoate,
      and HgCl2, but not by L-isoleucine, L-threonine, or L-serine. AMP, ADP, and ATP
      did not affect the enzyme activity. The N-terminal amino acid sequence was not
      similar to those of biosynthetic and biodegradative L-threonine dehydratases and
      L-serine dehydratases. The isolated tryptic phosphopyridoxyl peptide, however,
      contained a pyridoxal 5'-phosphate-binding consensus amino acid sequence of amino
      acid dehydratases.

PMID- 8743571
TI  - Characterization and biological significance of sialyl alpha 2-3galactosyl beta 1
      4xylosyl beta 1-(4-methylumbelliferone) synthesized in cultured human skin
      fibroblasts.
AB  - Human skin fibroblasts were incubated in the presence of a fluorogenic xyloside,
      4-methyl-umbelliferyl-beta-D-xyloside (Xyl-MU), then the cultured medium was
      recovered, concentrated with a lyophilizer, and dialyzed against distilled water.
      The structures of the Xyl-MU derivatives purified from the dialyzable fraction
      were investigated. In addition to established glycosaminoglycans-MU (GAGs-MU),
      Gal-Gal-Xyl-MU, Gal-Xyl-MU, sulphate-GlcA-Xyl-MU, GlcA-Xyl-MU, and Xyl-Xyl-MU,
      which were induced by Xyl-MU, an oligosaccharide having fluorescence was purified
      using a combination of gel filtration, ion-exchange chromatography and high
      performance liquid chromatography, then subjected to carbohydrate composition
      analysis, enzyme digestion, Smith degradation, 1H-NMR, and ion-spray mass
      spectrometric analysis. From the data obtained, the oligosaccharide was
      considered to have the structure SA alpha 2-3Gal beta 1-4Xyl beta 1-MU. The
      amount of MU-oligosaccharide in the cell culture increased with time and was
      dependent on the amount of Xyl-MU added. Its production was also different from
      that of Gal-Gal-Xyl-MU and Gal-Xyl-MU, which are biosynthetic intermediates of
      GAG-MU. Addition of CDP, an inhibitor of sialytransferase, to the cell culture
      medium increased the secretion of GAG-MU. These results suggest that SA-Gal-Xyl
      MU production may be related to the regulation of GAG-MU biosynthesis.

PMID- 8743572
TI  - Effects of point mutations at the flexible loop glycine-67 of Escherichia coli
      dihydrofolate reductase on its stability and function.
AB  - To elucidate the role of a flexible loop (residues 64-72) in the stability and
      function of Escherichia coli dihydrofolate reductase, glycine-67 in this loop was
      substituted by site-directed mutagenesis with seven amino acids (Ala, Cys, Asp,
      Leu, Ser, Thr, and Val). The circular dichroism spectra suggested that the
      confirmation of the native structure was affected by the mutations in both the
      presence and absence of NADPH. The free energy change of unfolding by urea
      decreased in the order of G67A > G67S > or = wild-type > or = G67D > G67T > G67C
      > or = G67L > G67V. The steady-state kinetic parameters for the enzyme reaction,
      Km and kcat, were only slightly influenced, but the rate of the hydride transfer
      reaction was significantly changed by the mutations, as revealed by the deuterium
      isotope effect on the enzyme activity. These results suggest that site 67 in the
      flexible loop, being very far from the active site, plays an important role in
      the stability and function of this enzyme. The characteristics of the mutations
      were discussed in terms of the modified flexibility of the native structure,
      compared with the results of mutations at site 121 in another flexible loop.

PMID- 8743573
TI  - Partial purification and characterization of a novel soybean protease which is
      inhibited by Kunitz and Bowman-Birk trypsin inhibitors.
AB  - A novel serine protease has been partially purified from dry seeds of the soybean
      (Glycine max) cultivar Keburi by cryoprecipitation at pH 6.4, fractional
      precipitation with ammonium sulfate, and a series of column chromatographic
      procedures on DEAE-Sepharose, SP-Sepharose, and Arginine-Sepharose 4B. Some
      properties of the purified enzyme were studied. The protease hydrolyzed the
      native storage globulins of soybean seeds, such as the alpha subunit of beta
      conglycinin, at a pair of arginine residues, Arg126-Arg127. The proteolysis of
      the alpha subunit in the purified alpha 2 beta molecule of beta-conglycinin
      apparently followed first order kinetics. The enzyme was inhibited by both
      soybean Kunitz trypsin inhibitor and Bowman-Birk proteinase inhibitor in a
      competitive manner. Moreover, the enzyme could catalyze the specific proteolysis
      of the A3 polypeptide of the purified G5 glycinin at the Arg99-Gly100 linkage, or
      the carboxyl side of the Arg98-Arg99 paired basic residues.

PMID- 8743574
TI  - N(omega)-phosphoarginine phosphatase (17 kDa) and alkaline phosphatase as protein
      arginine phosphatases.
AB  - Seven synthetic polymers, (Glu4, Tyr)n, (Arg)n, (Arg, Pro, Thr)n, (Arg-Gly-Glu)6,
      (Arg-Gly-Phe)6, (Glu-Arg-Gly-Phe)5, and (Ala-Leu-Arg-Arg-Ile-Arg-Gly-Glu-Arg)2,
      were treated with phosphoryl chloride to phosphorylate their Tyr, Thr, and Arg
      residues. Protamines and histones were phosphorylated similarly. These
      phosphorylated peptides were examined as to whether or not they serve as
      substrates for intestinal alkaline phosphatase [EC 3.1.3.1] and liver N(omega)
      phosphoarginine phosphatase [Kuba, M., Ohmori, H., and Kumon, A. (1992) Eur. J.
      Biochem. 208, 747-752]. Phosphorylated polyarginine was hydrolyzed with a lower
      Km with alkaline phosphatase than with N(omega)-phosphoarginine phosphatase,
      while the phosphorylated forms of (Arg-Gly-Phe)6 and culpeine were better
      substrates for N(omega)-phosphoarginine phosphatase. When (Arg, Pro, Thr)n and
      culpeine were phosphorylated chemically after treatment with phenylglyoxal, these
      phosphorylated peptides were worse substrates for N(omega)-phosphoarginine
      phosphatase than for alkaline phosphatase. Moreover, the results of proton
      decoupled 31P NMR analysis indicated that N(omega)-phosphoarginine phosphatase
      released Pi from N(omega)-phosphoarginine residues of phosphopeptides. These
      results indicate that both phosphatases function as protein arginine phosphatases
      in different manners, and that N(omega)-phosphoarginine phosphatase is useful for
      selectively detecting N(omega)-phosphoarginine residue in peptides containing
      various kinds of phosphorylated amino acids.

PMID- 8743575
TI  - Analysis of bile acids in urine specimens from healthy humans: determination of
      several bile acids with beta-hydroxyl and carbonyl groups.
AB  - Urinary bile acids of 39 healthy male undergraduates were analyzed by capillary
      gas chromatography and capillary gas chromatography-mass spectrometry. 3 alpha
      Hydroxy-12-oxo-5 beta-cholanoic acid, 3 alpha, 12 beta-dihydroxy-5 beta-cholanoic
      acid, 3 beta, 7 alpha-dihydroxy-5 beta-cholanoic acid, and 3 alpha, 7 alpha, 12
      beta-trihydroxy-5 beta-cholanoic acid, in addition to known bile acids, were
      identified and then quantified. The major part of the urinary bile acids was
      occupied by secondary bile acids. Every 7 beta-hydroxylated bile acid species was
      found in more than 80% of the subjects. The bile acid detected in the largest
      amount was 3 alpha-hydroxy-12-oxo-5 beta-cholanoic acid. The metabolites of
      cholic acid were quantitatively more predominant than those of chenodeoxycholic
      acid. These results indicate that bile acids with beta-hydroxyl and carbonyl
      groups at the C-3,7 and/or 12 positions are usual bile acids usually found in the
      urine of healthy humans. It is concluded that the occurrence of these bile acids
      is an effect of the intestinal bacterial flora and living conditions.

PMID- 8743576
TI  - Pore formation on proliferating yeast Saccharomyces cerevisiae cell buds by HM-1
      killer toxin.
AB  - The cytocidal effect of HM-1 produced by Hansenula mrakii on yeast Saccharomyces
      cerevisiae cells was studied. The HM-1 strongly inhibited the growth of S.
      cerevisiae cells at a low concentration (IC50: 2.1 x 10(-8) M) by reducing the
      number of viable cells. The killer action of HM-1 was most efficient when cells
      were actively proliferating. Cells in a resting state were resistant, but they
      became HM-1-sensitive after about 90 min of culturing at 30 degrees C,
      concomitantly with the increment of budding index. In association with the
      reduction of viable cell number, ultraviolet light-absorbing cellular components
      were discharged from sensitive cells. HM-1 molecules appear to bind to
      susceptible cells rather loosely since cells incubated with HM-1 were able to
      proliferate after having been washed. By phase-contrast light microscopy and
      scanning electron microscopy, discharge of cell material was observed at the
      budding portions of HM-1-treated cells. Addition of sorbitol to make the culture
      medium isotonic partially reduced the cell death induced by HM-1. These results
      suggest that HM-1 acts on the budding region of proliferating yeast cells,
      resulting in pore formation, leakage of cell material and eventual cell death.

PMID- 8743577
TI  - Reduced positive feedback regulation between myosin crossbridge and cardiac
      troponin C in fast skeletal myofibrils.
AB  - Several studies have shown that substitution of cardiac troponin C into fast
      skeletal muscle causes a marked reduction in cooperativity of Ca(2+)-activation
      of both myofibrillar ATPase and tension development. To clarify the underlying
      mechanisms, in the present study, Ca2+ binding to cardiac troponin C inserted
      into fast skeletal myofibrils was measured. Two classes of binding sites with
      different affinities (classes 1 and 2) were clearly identified, which were
      equivalent stoichiometrically to the two high-affinity sites (sites III and IV)
      and a single low-affinity site (site II) of troponin C, respectively. Ca2+
      binding to class-2 sites and Ca(2+)-activation of myofibrillar ATPase occurred in
      roughly the same Ca2+ concentration range, indicating that site II is responsible
      for Ca2+ -regulation. Myosin crossbridge interactions with actin, both in the
      presence and absence of ATP, enhanced the Ca2+ binding affinity of only class-2
      sites. These effects of myosin crossbridges, however, were much smaller than the
      effects on the Ca2+ binding to the low-affinity sites of fast skeletal troponin
      C, which are responsible for regulating fast skeletal myofibrillar ATPase. These
      findings provide strong evidence that the reduction in the cooperative response
      to Ca2+ upon substituting cardiac troponin C into fast skeletal myofibrils is due
      to a decrease in the positive feedback interaction between myosin crossbridge
      attachment and Ca2+ binding to the regulatory site of troponin C.

PMID- 8743578
TI  - Effect of exogenous decorin on cell morphology and attachment of decorin
      deficient fibroblasts.
AB  - We have reported deficient expression of decorin on skin fibroblasts from a
      patient with carbohydrate-deficient glycoprotein syndrome type I [Gu, J. and
      Wada, Y. (1995) J. Biochem. 117, 1276-1279]. The characteristics of fibroblasts
      from this patient included increased cell spreading and reduced proliferation. We
      analyzed the expression of other extracellular matrix proteins by Western and
      Northern blot analyses, and found that adhesion molecules, fibronectin, and type
      I collagen, were increased, whereas an anti-adhesion molecule, tenascin, was
      decreased, like decorin. Subsequently, decorin was purified from bovine tendons,
      and cultured with these fibroblasts in fibronectin-depleted culture medium.
      Exogenous decorin inhibited cell attachment to a plastic culture dish in a dose
      dependent manner, while dermatan sulfate did not. The cell morphology was
      markedly normalized by decorin, but proliferation was not restored. These
      findings suggest that decorin exhibits an anti-adhesion property in a fibroblast
      culture system and that the deficiency is responsible for the morphological
      change observed in this patient's fibroblasts.

PMID- 8743580
TI  - Analysis of protein carbonyls with 2,4-dinitrophenyl hydrazine and its antibodies
      by immunoblot in two-dimensional gel electrophoresis.
AB  - Protein carbonyls are reported to increase in aging and in pathologies such as
      Alzheimer's disease and ischemic injury. Detailed study of this important issue
      has, however, been hampered by lack of an appropriate method to identify
      individual carbonylated proteins. We describe here an immunoblot method to
      identify individual carbonylated proteins. We describe here an immunoblot method
      to investigate protein carbonyls reactive to 2,4-dinitrophenyl hydrazine. Rabbit
      polyclonal antibodies against 2,4-dinitrophenyl hydrazine were used to study the
      proteins derivatized by the reagent in one- or two-dimensional polyacrylamide gel
      electrophoresis followed by immunoblotting. More than 25 proteins with high
      carbonyl contents were clearly demonstrated in two-dimensional immunoblot of rat
      tissue soluble proteins. The method could detect concentrations as low as 1 pmol
      of carbonyls. The signals were mostly abolished by prior treatment of tissue
      proteins with sodium borohydride to reduce carbonyls. Fragments generated by V8
      protease digestion of a single protein exhibited signal intensities of varying
      degrees, indicating that carbonylation is not uniform in different amino acid
      sequences. Proteins treated with glucose or aldehydes gave rise to positive
      signals, suggesting that the finding of carbonyls in tissue proteins is not
      necessarily an indication of direct oxidation of side chains of amino acid
      residues.

PMID- 8743579
TI  - A catalogue of genes in mouse embryonal carcinoma F9 cells identified with
      expressed sequence tags.
AB  - We used expressed sequence tags (ESTs) to identify genes expressed in mouse
      embryonal carcinoma F9 cells and prepared 2132 ESTs from undifferentiated F9 cDNA
      libraries: 1026 were prepared after randomly selecting clones from one of the
      libraries and the remaining 1106 ESTs were prepared after classifying 2896 clones
      of the libraries into four classes, according to the levels and patterns of
      expression. Among the former 1026 ESTs, 797 (78%) matched known genes, 61 (6%)
      matched database sequences of uncharacterized cDNAs, and 168 (16%) represented
      novel genes. The ESTs matching known genes were catalogued according to putative
      structural and cellular functions. As many as 53% were related to transcription
      and translation, and 19% were related to energy metabolism, including transcripts
      of mitochondrial DNA. These percentages were significantly higher in F9 cells
      than in the human heart and brain, and a human liver cell line, HepG2. We found
      that approximately 7% of the ESTs corresponding to low-abundance mRNAs are either
      related to retinoic acid-regulated genes or mammalian development- and/or
      differentiation-related genes. Cataloguing of the genes expressed in the F9 cells
      paves the way for isolating genes involved in early mammalian development.

PMID- 8743581
TI  - Two mitochondrial 3-hydroxyacyl-CoA dehydrogenases in bovine liver.
AB  - 3-Hydroxyacyl-CoA dehydrogenase catalyzes the third reaction of fatty acid beta
      oxidation spiral. There are three enzymes catalyzing the 3-hydroxyacyl-CoA
      dehydrogenase, mitochondrial enoyl-CoA hydratase/3-hydroxyacyl-CoA
      dehydrogenase/3-ketoacyl-CoA thiolase trifunctional protein, and peroxisomal
      enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase CoA dehydrogenase was not
      known. In the present study, two monofunctional mitochondrial 3-hydroxyacyl-CoA
      dehydrogenases were purified from bovine liver. Type I enzyme was composed of two
      identical subunits with molecular mass of 35 kDa, and type II enzyme was a
      homotetramer of a 28 kDa polypeptide. In respect to the molecular structures,
      immunochemical properties, and carbon chain length specificities of acyl-CoA
      substrates, type I enzyme was the same as the well-known classical enzyme
      purified from various tissues, but type II enzyme was concluded to be a new
      enzyme. Type I enzyme was ubiquitous, but type II enzyme was rich in bovine and
      sheep, of several animal livers so far examined.

PMID- 8743582
TI  - Two phosphorylations specific to the tail region of the 204-kDa heavy chain
      isoform of porcine aorta smooth muscle myosin.
AB  - In a porcine aorta extract, we observed two protein kinase activities which
      specifically phosphorylate the 204-kDa heavy chain isoform of aorta myosin in the
      absence of conventional kinase activators. We referred to these two protein
      kinases, eluted at 0.15 and 0.2 M KCl from a DEAE-column, as myosin kinases I
      (MKI) and II (MKII), respectively. The phosphorylation site for MKI was
      determined using a purified phosphopeptide derived from porcine aorta myosin
      phosphorylated with MKI. By comparison with the deduced amino acid sequence for
      smooth muscle myosins, the site corresponded to a Ser located at 3 amino acids
      upstream from a Pro, the putative end of the alpha-helical segment of the 204-kDa
      heavy chain tail. A homologous Ser is only present in smooth muscle myosins, i.e.
      not in nonmuscle myosins. MKI was purified 130-fold, but not separated from a
      kinase activity phosphorylating Ser1 or Ser2 in the 20-kDa regulatory light chain
      of aorta myosin. In contrast, MKII was purified to near homogeneity. MKII
      phosphorylated the porcine aorta myosin heavy chain at a Ser 19 amino acids
      downstream from the MKI site. The amino acid sequence around the Ser shared a
      consensus sequence of the phosphorylation site. The amino acid sequence around
      the Ser shared a consensus sequence of the phosphorylation site for casein kinase
      II and was homologous to that reported for bovine aorta myosin [Kelley, C.A. and
      Adelstein, R.S. (1990) J Biol. Chem. 265, 17876-17882]. MKII was identified as a
      multifunctional protein kinase, casein kinase II.

PMID- 8743583
TI  - F-actin bundling activity of Tetrahymena elongation factor 1 alpha is regulated
      by Ca2+/calmodulin.
AB  - Translation elongation factor 1 alpha (EF-1 alpha) catalyzes the GTP-dependent
      binding of amino-acyl-tRNA to the ribosome. Previously, Tetrahymena 14-nm
      filament-associated protein was identified as EF-1 alpha [Kurasawa et al. (1992)
      Exp. Cell Res. 203, 251-258]. This and several other studies suggest that EF-1
      alpha functions not only in translation but also in regulation of some part of
      the cytoskeleton. Tetrahymena EF-1 alpha bound to F-actin and induced bundling of
      F-actin. We investigated the effects of GTP/GDP and Ca2+/calmodulin on F-actin
      bundling activity of EF-1alpha. The presence of GTP, GDP, or guanylyl
      imidodiphosphate (GMP-PNP) slightly decreased the amount of EF-1 alpha which
      bound to F-actin, but each had virtually no effect on the F-actin bundling
      activity. The formation of F-actin bundles by EF-1 alpha was Ca(2+)-insensitive.
      In the absence of Ca2+, calmodulin did not bind to EF-1 alpha and F-actin. On the
      other hand, in the presence of Ca2+, calmodulin directly bound to EF-1 alpha but
      did not have any serious influence on EF-1 alpha/F-actin binding. Under the
      conditions, electron microscopy demonstrated that Ca2+/calmodulin completely
      inhibited the F-actin bundling by EF-1 alpha. These results indicate that
      CA2+/calmodulin regulates the F-actin bundling activity of EF-1 alpha without
      inhibition of the binding between Ef-1 alpha and F-actin.

PMID- 8743584
TI  - Androgenic control of 1-alkyl-2,3-diacylglycerol in the harderian gland of the
      golden hamster, Mesocricetus auratus.
AB  - Harderian glands of golden hamsters produce a copious lipid secretion, most of
      which is in the form of 1-alkyl-2,3-diacylglycerol (ADG). Sexual differences are
      seen in the composition of golden hamster ADG and in the morphology of secretory
      lipid droplet. ADGs from females contained abundant iso- and anteiso-branched
      chain alkyl groups and fatty acids [Seyama, Y., Otsuka, H., Ohashi, K., Vivien
      Roels, B., and Pevet, P. (1995) J. Biochem. 117, 661-670]. Female hamsters were
      either untreated or given subcutaneous testosterone pellets. Treatment of females
      with testosterone led to the disappearance of such branched chain alkyl groups
      and fatty acids. Intact males had ADGs with entirely saturated straight chain
      alkyl groups and fatty acids. Castration led to the appearance of iso- and
      anteiso-branched chain alkyl groups and fatty acids. These observations suggested
      that the production of branched chain fatty acids in the Harderian gland of
      golden hamster is inhibited by testosterone at the step of isovaleryl-CoA
      dehydrogenase and 2-methyl branched-chain acyl-CoA dehydrogenase

PMID- 8743585
TI  - Formation of a triple-stranded DNA between d(GGA:TCC) repeats and d(GGA) repeat
      oligonucleotides.
AB  - Incubation of the 162-bp duplex containing d(GGA:TCC)11 repeats with d(GGA)11 and
      d(GGT)11 oligonucleotides, but not with d(TCC)11, gave a mobility-shifted band in
      polyacrylamide gel electrophoresis, suggestive of the triplex formation. The two
      conformers, however, showed difference in binding affinity and structure. The
      complex formed with d(GGT)11 exhibited patterns protected from DNase I digestion
      and from modifications with osmium tetroxide and dimethyl sulfate. The patterns
      were conformed to a proposed triplex model. In contrast, the complex with
      d(GGA)11 was sensitive to DNase I and to osmium tetroxide, which is reactive to
      pyrimidine bases of single-stranded DNA. These results suggest that the
      d(GGA:TCC)11 and d(GGA)11 triple-stranded complex forms a D-loop-like structure.
      By considering the ability of d(GGA)11 oligonucleotides to form a parallel
      homoduplex, the structure may be one in which the GGA-strand of the duplex pairs
      with d(GGA)11 in parallel, with the TCC-strand being looped out.

PMID- 8743586
TI  - Characterization of a B. subtilis minor isoleucine tRNA deduced from tDNA having
      a methionine anticodon CAT.
AB  - Bacillus subtilis, which belongs to Gram-positive eubacteria, has been predicted
      to have a minor isoleucine tRNA transcribed from the gene possessing the CAT
      anticodon, which corresponds to methionine. We isolated this tRNA and determined
      its sequence including modified nucleotides. Modified nucleotide analyses using
      TLC, UV, and FAB mass spectroscopy revealed that the first letter of the
      anticodon is modified to lysidine [4-amino-2-(N6-lysino)-1-beta-d-ribofuranosyl
      pyrimidine]. As a result, this tRNA agrees with the minor one predicted from the
      DNA sequence and is thought to decode the isoleucine codon AUA.

PMID- 8743587
TI  - The protective role of glutathione peroxidase in apoptosis induced by reactive
      oxygen species.
AB  - Selenium-dependent glutathione peroxidase (GPx) plays a protective role in
      oxidative stress-induced apoptosis. In this study, we demonstrated that MDBK
      cells, a bovine renal epithelial cell line, exhibited internucleosomal DNA
      fragmentation characteristic of apoptotic cell death under selenium-deficient
      conditions with lower doses of hydrogen peroxide (H2O2) than under selenium
      supplemented ones. This was due to a decreased amount of GPx in the cells under
      selenium-deficient conditions, because other antioxidative enzyme activities were
      not affected by the selenium supplementation. Cumene hydroperoxide also induced
      DNA fragmentation in selenium-deficient cells but no ladder formation was
      observed. Flow cytometric analysis showed that selenium-deficient cells were less
      capable of scavenging intracellular peroxides after exposure to exogenous H2O2
      than selenium-supplemented ones. In contrast, there was no difference in
      viability between selenium-supplemented and non-supplemented cells in cell
      survival after exposure to menadione, which activates the electron transport
      system and increases intracellular superoxide radicals. Clofibrate, a peroxisomal
      proliferator and an inducer of catalase (CAT), partially protected both Se
      deficient and Se-supplemented cells from exogenous H202. We concluded that
      selenium-deficient cells were more easily brought to apoptotic cell death by
      peroxides, but not by superoxide radicals, than selenium-supplemented ones and
      that CAT could compensate for the depletion of GPx to a certain degree by
      scavenging H2O2.

PMID- 8743589
TI  - Effects of caffeine, practice, and mode of presentation on Stroop task
      performance.
AB  - A series of experiments were designed to investigate the effects of 125 and 250
      mg caffeine, or placebo, on performance of the Stroop task. Caffeine had no
      effect on performance of either the classic colour-word version or a numerical
      version of the task, either using computerised presentation of the stimuli or a
      traditional card version. However, significant practice effects were found using
      a within-subjects design with the card version of the task, and differences were
      found between performance in the card and computerised versions of the task. It
      is concluded that at these doses, caffeine does not significantly affect Stroop
      performance. It is also suggested that practice effects in studies using within
      subject designs may be a problem when attempting to detect subtle effects of
      drugs on cognitive performance, and that the computerised version of the Stroop
      task may not be an exact analogue of the traditional card version.

PMID- 8743588
TI  - Isolation, chemical characterization, and subcellular distribution of 1-O-alkyl-2
      acetyl-sn-glycerol in Tetrahymena pyriformis cells.
AB  - 1-O-Hexadecyl-2-acetyl-sn-glycerol, the immediate precursor of platelet-
      activating factor (PAF) in its de novo formation, was detected in the protozoon
      Tetrahymena pyriformis. It was purified from the total lipid extract by TLC,
      after successive developments in two different solvent systems. Characterization
      was assessed by (a) gas-liquid chromatography with electron capture detection,
      and (b) gas chromatography combined with mass spectrometry in selected ion
      monitoring mode, after derivatization with heptafluorobutyric acid anhydride and
      tert-butyldimethylchlorosilane/imidazole, respectively. Its quantity was found to
      be 0.1 nmol/10(7) cells from the GC-MS, using authentic alkylacetylglycerol as
      external standard. Cell fractionation revealed that alkylacetylglycerol is
      located exclusively in the microsomal fraction of the protozoon. Previously, we
      have reported the occurrence of PAF in the microsomal fraction, as well as a
      dithiothreitol-insensitive CDP-choline: cholinephosphotransferase activity that
      utilizes exogenous alkylacetylglycerol as substrate in the mitochondrial and
      microsomal fractions. The above findings indicate that PAF can be formed in the
      cell by the de novo pathway.

PMID- 8743591
TI  - Inhibitory effect of restraint on induction of behavioral sensitization to
      methamphetamine and cocaine in mice.
AB  - Repeated intermittent (generally 3-day intervals) administrations of
      methamphetamine (MAP: 2 mg/kg, SC) or cocaine (COC: 20 mg/kg, SC) induced
      sensitization to the ambulation-increasing effect of individual drug in mice. The
      induction of MAP and COC sensitization was inhibited when restraint of the mouse
      (putting the mouse in a jar of 6 cm in diameter for 3 and 2 h after
      administration of MAP and COC, respectively) was started immediately after each
      drug administration. Furthermore, the induction of sensitizations to MAP and COC
      was significantly reduced when the restraint was started within 1/4 h and 1/6 h
      after the administration of MAP and COC, respectively, whereas the restraint
      starting thereafter did not affect the induction of sensitization. The three
      times repeated administrations of saline with or without restraint did not
      significantly change the sensitivities to MAP and COC. The ambulation-increasing
      effects of MAP and COC reached the peak at approximately 2/3 and 1/2 h,
      respectively, and persisted for 3 and 2 h after the administration. The present
      results suggest that, to completely induce sensitization to MAP and COC in terms
      of ambulation, the mice must freely move for at least half of the latency to
      their peak effects.

PMID- 8743590
TI  - Effects of cold acclimation and central opioid processes on thermoregulation in
      rats.
AB  - Two experiments, using centrally administered [D-Ala2-MePhe4-Gly(ol)5]enkephalin
      (DAMGO), a selective mu-opioid agonist, assessed the thermoregulatory
      consequences of cold acclimation. Experiment 1 assessed whether cold acclimation
      influenced DAMGO hyperthermia at room temperature. Sialo-adenectomized rats were
      implanted with ICV cannulae and IP Mini-Mitters. After 3 weeks of exposure to 5
      degrees C (cold acclimation) or 22 degrees C (non-cold acclimation) rats were
      pretreated with IP naltrexone HCl (2 mg/kg b.wt.) or vehicle (0.15 M saline) and
      later administered a 5-microliters ICV injection of 0.15 M saline, 0.1, or 1.0
      microgram DAMGO. Cold acclimation exerted little effect on core temperature but
      potentiated DAMGO hyperthermia in a dose-dependent, naltrexone-reversible,
      activity-independent manner. Experiment 2 assessed the effect these same
      manipulations exerted on operant escape from a convective source of mild heat (37
      degrees C). Duration of heat escape increased with cold acclimation in a
      naltrexone-resistant manner, yet was not influenced by DAMGO in either non-cold
      acclimated or cold-acclimated rats. These findings suggest that two central
      adaptations occur with cold acclimation: A non-mu-opioid process that increases
      heat sensitivity and a mu-opioid process that potentiates hyperthermia but fails
      to alter heat escape due to mu-opioid-mediated analgesia.

PMID- 8743592
TI  - Naloxone decreases intake of 10% sucrose in preweanling rats.
AB  - To investigate the role of opioids in the mediation of sucrose intake in the
      preweanling rat pup, we measured the effect of naloxone on intake of pups licking
      10% sucrose from the floor of a beaker (independent ingestion test) and of pups
      ingesting 10% sucrose that was continuously infused through an anterior,
      sublingual oral catheter (oral catheter test). Pups were tested only once to
      eliminate the possible effect of test experience. Pups were tested in the second
      postnatal week (PN7, 9, 10, 11, and 14 days) with naloxone (1 mg/kg) or vehicle
      controls. Fourteen-day-old pups were also tested with 0.1 and 0.5 mg/kg. Naloxone
      began to be efficacious for inhibiting intake on PN10 in the oral catheter test
      and on PN11 in the independent ingestion test. On PN14, the inhibition of intake
      was dose related and naloxone was more potent for inhibiting intake in
      independent ingestion tests than in oral catheter tests. Naloxone not only
      decreased intake, it also decreased the incidence of licking, increased mouthing
      and resting, and had no significant effect on locomotion. The site of the
      inhibitory effect of naloxone on intake was in the central nervous system,
      presumably in the brain, because naloxonemethiodide, an analogue of naloxone that
      does not cross the blood-brain barrier, did not inhibit sucrose in either test.
      These results demonstrate that the intake of 10% sucrose depends on endogenous
      opioids as early as PN10 and that this opioid mechanism operates when pups have
      not had prior test experience and in a test (oral catheter test) where intake is
      not dependent on appetitive behaviors.

PMID- 8743593
TI  - Methadone produces conditioned place preference in the rat.
AB  - The appetitive properties of methadone were investigated using the conditioned
      place preference paradigm. Male Sprague-Dawley rats received conditioned place
      preference training for a 6-day period. The apparatus consisted of two chambers
      with distinctive visual and tactile cues, separated by removable doors. Rats
      received intraperitoneal (IP) injections of methadone (1.0, 2.0, 4.0, 6.0, 8.0,
      and 10.0 mg/kg methadone HCl) paired with one chamber and saline paired with the
      other chamber on alternating days. On the seventh day, rats were allowed free run
      of the entire apparatus and time spent in either chamber was computer recorded.
      Methadone produced a place preference for the side previously paired with drug in
      a dose-dependent manner. Place preference for methadone peaked at 4.0 mg/kg and
      aversion was produced at 10.0 mg/kg. These results indicate that at intermediate
      doses, methadone does have appetitive properties and is capable of producing a
      conditioned place preference.

PMID- 8743594
TI  - Possible novel pharmacodynamic action of cocaine: cardiovascular and behavioral
      evidence.
AB  - Intravenous cocaine (0.03-3 mg/kg) produced two distinct and temporally separable
      effects in rats. One is an initial, large, and brief increase in blood pressure
      (BP) and heart rate (HR) of a rapid onset (abrupt hemodynamic stimulation). A
      rapid, brief, and intense behavioral arousal accompanied this abrupt hemodynamic
      stimulation. The other effect of cocaine is a prolonged locomotor activation of a
      relatively slower onset. Prolonged increases in BP and HR accompanied this
      locomotor effect. The threshold doses of cocaine to produce abrupt hemodynamic
      stimulation and locomotion are 0.03 and 0.3 mg/kg, respectively. Dopamine
      receptor antagonists, SCH 23390 or eticlopride, at a 0.03 mg/kg dose antagonized
      the locomotion and the parallel prolonged increases in BP and HR, but not the
      initial brief behavioral arousal and abrupt hemodynamic stimulation responses to
      cocaine. Peripheral dopamine receptor antagonist, domperidone, altered neither
      behavioral nor cardiovascular effects of cocaine. Chlorisondamine (1 mg/kg), an
      autonomic ganglionic blocker, did not alter either the initial brief behavioral
      arousal or the locomotor responses to cocaine, but it prevented the
      cardiovascular changes that accompanied both these behavioral responses.
      Norepinephrine, a direct adrenergic vasoconstrictor, although produced rapid and
      large increase in BP, did not cause abrupt behavioral arousal or locomotor
      activation. Unlike cocaine, monoamine reuptake inhibitors that are selective for
      norepinephrine (nisoxetine, 0.1-1 mg/kg) or serotonin (fluoxetine, 0.3-3 mg/kg)
      produced neither brief behavioral arousal and abrupt hemodynamic stimulation nor
      locomotor activation. Dopamine-selective reuptake inhibitor, GBR 12,909, also did
      not elicit the initial brief behavioral arousal and abrupt hemodynamic
      stimulation. But, GBR 12,909, like cocaine, produced a prolonged locomotor effect
      and parallel increases in BP and HR. These effects of GBR 12,909 were prevented
      by SCH 23,390 and eticlopride, but not by domperidone. Similar to cocaine,
      cardiovascular, but not the locomotor effects of GBR 12,909 were prevented by
      chlorisondamine. Lidocaine (0.3-3 mg/kg), a sodium channel blocker and local
      anesthetic, produced neither behavioral nor physiological changes. Both cocaine
      (3 mg/kg) and GBR 12,909 (1 mg/kg) increased plasma norepinephrine and
      epinephrine concentrations. These increases were antagonized by both eticlopride
      and SCH 23,390. These results indicate that behavioral and cardiovascular effects
      of cocaine are intricately related with respect to the molecular mechanisms
      involved. Two pharmacodynamic actions of cocaine appear to mediate these effects.
      One is a dopamine-dependent while the other is a monoamine- and sodium channel
      independent novel action. The former mediates cocaine's locomotor effect and the
      accompanying prolonged increases in BP and HR, while the latter mediates the
      initial brief behavioral arousal and the accompanying abrupt hemodynamic
      stimulation.

PMID- 8743595
TI  - Behavioral effects of the putative anxiolytic (+/-)-1-(2,5-dimethoxy-4
      ethylthiophenyl)-2-aminopropane (ALEPH-2) in rats and mice.
AB  - Behavioral effects of the phenethylamine derivative (+/-)-1-(2,5-dimethoxy-4
      ethylthiophenyl)-2-aminopropane (ALEPH-2) were studied in mice and rats. Murine
      locomotor activity, measured with a photocell actometer, was markedly depressed
      following IP injection of 2 and 6 mg/kg of the drug. The same doses of the drug
      also decreased frequency and duration of head dipping and the number of rearings
      in the hole board apparatus. In the murine elevated plus maze 2 and 6 mg/kg of
      ALEPH-2 increased the percentage of both open arm entries and time. The total
      number of entries into the enclosed arms was not significantly affected by the
      drug. In the rat, 2-12 mg/kg ALEPH-2, IP, decreased photobeam counts in the
      actometer in a dose-dependent fashion. Both 2 and 4 mg/kg of the drug increased
      the percentage of open arm entries, but only the highest dose significantly
      increased the percentage of time spent on the open arms. The dose of 4 mg/kg
      ALEPH-2 also significantly decreased the total number of enclosed arm entries.
      Finally, in a recently developed model of anxiety and memory, the elevated T
      maze, the doses of 2 and 4 mg/kg ALEPH-2 did not change inhibitory avoidance of
      the open arms. Nevertheless, the highest dose had an amnestic effect on this
      task, repeated 72 h later in the absence of drug. In addition, this dose
      significantly increased the latency to escape from the open arms and had an
      amnestic effect measured 72 h later. Overall, these results indicate that ALEPH-2
      possesses anxiolytic, amnestic as well as sedative and/or motor depressant
      actions.

PMID- 8743596
TI  - Supraspinal delta 2 opioid agonist analgesia in Swiss-Webster mice involves
      spinal GABAA receptors.
AB  - The tail-flick response is a spinal reflex that can be modulated by
      administration of antinociceptive agents supraspinally through activation of
      descending systems and involvement of the action of neurotransmitters in the
      spinal cord. Descending noradrenergic and serotonergic systems are involved in
      morphine (and other mu opioid receptor agonists)-induced antinociception. These
      descending systems, however, are not involved in supraspinal delta opioid
      receptor agonist-induced antinociception. Recently, a descending system mediated
      by spinal gamma-aminobutyric acid (GABA) A and B receptors has been demonstrated
      to be involved in the antinociceptive action of delta 1 opioid receptor agonists
      ([D-Pen2,5]enkephalin in ICR mice and [D-Pen2,5]enkephalin and heroin in Swiss
      Webster mice). In the present study, the involvement of spinal GABAA receptors in
      the antinociceptive action of supraspinal delta 2 opioid receptor agonists, [D
      Ser2]-Leu-enkephalin-Thr and 6-monoacetylmorphine, action was demonstrated. The
      intrathecal administration of GABAA receptor antagonists, bicuculline and
      picrotoxin, inhibited the antinociceptive action of both [D-Ser2]-Leu-enkephalin
      Thr and 6-monoacetylmorphine given intracerebroventricularly. The intrathecal
      administration of 2-hydroxysaclofen, a GABAB receptor antagonist, had no effect.
      These studies suggest that supraspinal delta 2, like delta 1, opioid receptor
      action involves spinal GABAA receptors, but delta 2, unlike delta 1, action does
      not involve GABAB receptors. Thus, the supraspinal delta 1 agonist action
      (heroin, DPDPE) and the delta 2 agonist action (6MAM, DSLET) can be further
      differentiated by the selectivity of the spinal GABA receptors involved in Swiss
      Webster mice.

PMID- 8743597
TI  - Morphine- and cocaine-induced conditioned place preference: effects of quinpirole
      and preclamol.
AB  - The role of dopamine in opioid reward is unresolved. Furthermore, the issue is
      somewhat unclear regarding cocaine and the place preference paradigm. In the
      present study we investigated whether the drugs activating dopamine autoreceptors
      affect cocaine- and morphine-induced place preference in rats. Neither the
      dopamine D2/D3 receptor agonist, quinpirole (0.05 mg/kg, SC), nor the partial
      dopamine autoreceptor agonist, preclamol (2 or 8 mg/kg, SC), induced place
      conditioning by itself. Quinpirole had no significant influence on the place
      preference induced either by morphine (3 mg/kg, SC) or cocaine (5 mg/kg, IP).
      Preclamol, when given at the dose of 8 mg/kg SC, significantly attenuated the
      effect of cocaine but failed to modify the effect of morphine. Our results
      suggest that the rewarding properties of morphine involve DA-independent
      mechanisms whereas in the cocaine-induced reward the role of brain DA is
      critical. Furthermore, as regards place conditioning, we propose that the
      activation of DA autoreceptors is not sufficient to reliably modify the rewarding
      effect of cocaine.

PMID- 8743598
TI  - Further investigation of allopurinol effects on MPTP-induced oxidative stress in
      the striatum and brain stem of the rat.
AB  - Levels of uric acid, xanthine, hypoxanthine, ascorbic acid (AA), dehydroascorbic
      acid (DHAA), glutathione (GSH), noradrenaline (NA), dopamine (DA),
      dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine
      (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ion (MPP+) were
      determined in the striatum and/or in the brain stem of 3-month-old male Wistar
      rats given allopurinol (300 mg/kg day by gavage) for 3 days before a single MPTP
      35 mg/kg dose IP. Allopurinol alone decreased uric acid and increased xanthine
      levels both in the striatum and in the brain stem; moreover, allopurinol
      decreased striatal DOPAC + HVA/DA ratio and increased 5-HIAA/5HT ratio in the
      brainstem. Allopurinol affected neither regional MPTP nor MPP+ disposition.
      Allopurinol potentiated the MPTP-induced decrease in the DOPAC+HVA/DA ratio and
      increase in striatal AA oxidation; in addition, allopurinol antagonised the MPTP
      induced: (i) increase in uric acid levels; (ii) decrease in NA levels in both
      regions, in DA levels, and in the 5-HIAA/5-HT ratio in the brain stem: (iii)
      increase in AA oxidation in the brain stem. In conclusion, the MPP(+)-induced
      oxidative stress mediated by xanthine oxidase seems to be involved in DA
      depletion in the brainstem and in NA depletion in both regions; moreover,
      striatal uric acid may have an active role in the neuronal antioxidant pool.

PMID- 8743599
TI  - Changes in monoamines and their metabolite concentrations in REM sleep-deprived
      rat forebrain nuclei.
AB  - Rapid eye movement sleep deprivation (REMSD) is a potent stressor in rats.
      Behavioral abnormalities such as passive and active avoidance, locomotor
      activity, problem solving, sensory information processing, and the development of
      adaptive copping strategy in response to repeated stress are among the earliest
      obvious symptoms of REMSD, the mechanism for which remain largely unknown. The
      aim of this study was to determine whether 96 h of REMSD causes changes in
      monoamine neurotransmitters concentrations in rat forebrain regions (frontal
      cortex, FC; parietal cortex, PC, and striatum) that are involved in mediating
      higher brain functions such as attentional mechanisms, sensory information
      processing, and locomotor activity, which are severely affected in REMSD
      conditions. Rats were subjected to 96 h of REMSD using inverted flower pot water
      tank technique. To account for the stress associated with water tanks, a tank
      control group (TC) was included where the animals could reside comfortably on a
      large pedestal in the water tank. Regional brain concentrations of norepinephrine
      (NE), dopamine (DA), dihydroxyphenyacetic acid (DOPAC), L-3,4
      dihydroxyphenylalanine (L-DOPA), homovanillic acid (HVA), 5-hydroxytryptamine (5
      HT), and 5-hydroxyindoleacetic acid (HIAA) were determined by electrochemical
      detection using high-performance liquid chromatography. The concentrations of
      serotonin and its metabolite, HIAA, was reduced in the frontal and parietal
      cortexes of REMSD rats compared with TC or cage control (CC) group. NE, DA,
      DOPAC, and HVA concentrations in FC and PC of REMSD animals were remained
      unchanged compared with TC or CC rats. A significant increase in the
      concentrations of DA metabolites was observed in the striatum of REMSD rats when
      compared with CC and TC rats. There was a 29 and 31% increase in the
      concentration of striatal DA in REMSD group compared to the TC and CC groups,
      respectively; however, these percentages were not statistically different.
      Striatal NE, 5-HT, and HIAA concentrations were not significantly different among
      the three groups. These results suggest that 96 h of REMSD alters dopaminergic
      and serotonergic systems in different locations in rat brain. The effect of REMSD
      on the serotonergic systems are localized in the cerebral cortex, whereas
      dopaminergic metabolism is increased in the striatum.

PMID- 8743600
TI  - Diazepam modulates the period of locomotor rhythm in mice (Mus booduga) and
      attenuates light-induced phase advances.
AB  - Experiments were carried out on the continuous action of diazepam
      (benzodiazepine) offered through drinking water in 2% ethanol on psi and tau of
      the activity rhythms under LD (12:12) and DD conditions. Under entraining
      conditions diazepam failed to evoke striking changes in psi. On the other hand,
      under free-running conditions period-lengthening and period-shortening effects
      were observed. Further experiments conducted on the continuous effect of diazepam
      on light pulse evoked phase shifts revealed that phase advances were attenuated
      significantly in diazepam-treated animals at CT 20 and 24. These results were
      discussed with regard to the action of diazepam on the light sensitivity of the
      circadian pacemaker.

PMID- 8743601
TI  - Ethanol anapyrexia in rats.
AB  - In the present series of experiments we tested whether ethanol decreases body
      temperature by impairing thermal regulation (poikilothermia) or by shifting the
      set point downwards. The central temperature of rats kept in a thermocline and
      the selected ambient temperature were recorded by telemetry. After an IP
      injection of 2 g/kg of ethanol the rats selected an ambient temperature 7 degrees
      C lower than the one they selected before the ethanol injection and 8 degrees C
      lower than the one selected by the same rats after saline injection. At the same
      time the central temperature decreased by 2.5 degrees C. After about 40 min the
      rats preferred warmer ambient temperatures and 10 min later the central
      temperature began to rise. When, after ethanol, the rats were kept at 30 degrees
      C the central temperature remained at the normal level. At 35-36 degrees C the
      central temperature of normal rats without ethanol rose, in 1 h, from 37 degrees
      C to 39.75 degrees C. The results suggest that ethanol hypothermia is due to a
      downward shift of the set point and, in fact, is an anapyrexia, a condition
      inverse to fever.

PMID- 8743602
TI  - Ca2+/calmodulin system: participation in the progesterone-induced facilitation of
      lordosis behavior in the ovariectomized estrogen-primed rat.
AB  - We studied the effect some drugs that participate in the Ca2+/ calmodulin system
      have on the progesterone (P) facilitation of lordosis behavior in ovariectomized
      estradiol (E2) primed rats. We injected rats 44 h after E2 priming with 2 mg P
      together with various dosages of one of the following compounds: pentobarbital,
      trifluoperazine (TPZ), promethazine (PMZ), Chlorpromazine (CPZ), haloperidol
      (HAL), pimozide (PIM), and verapamil (VER). Then 4 h after treatment, animals
      were tested for sexual behavior, expressed as the lordosis quotient (LQ). All
      drugs at 4 mg/kg or higher inhibited lordosis, but only HAL, PIM, and VER were
      active at 1 mg/kg. The maximum level of activity was shown by PIM, although at
      the dose of 8 mg/kg no statistical differences were found between this compound
      and TPZ or HAL. Pentobarbital (25 mg/kg) showed no significant difference from
      saline-treated controls. The activity of the tested drugs on the facilitation of
      sexual behavior appears to be related to their efficiency as inhibitors of
      calmodulin (CaM)-dependent phosphodiesterase and as ligands for the Ca(2+)-CaM
      complex.

PMID- 8743603
TI  - Salbutamol antagonizes insulin- and sodium mercaptoacetate-induced but not 2
      deoxy-D-glucose-induced hyperphagia.
AB  - The role of beta-adrenoreceptors in modulating feeding in glucoprivation- and
      lipoprivation-induced hyperphagias was studied in rats by measuring the efficacy
      of the selective beta2-adrenoreceptor agonist salbutamol to antagonize the
      hyperphagic response induced by injection of 2-deoxy-D-glucose (2-DG), insulin,
      or sodium mercaptoacetate (MA). 2-DG and insulin are blockers of glucose
      utilization, and their administration stimulates receptor cells that are
      selectively sensitive to central glucose availability. MA stimulates feeding in
      rats maintained on a fat-supplemented diet, by blocking fatty acid oxidation at
      different levels in the metabolic pathway. We found that salbutamol dose
      dependently antagonized both the insulin- and MA-induced hyperphagia, with
      reductions in food intake up to 100% compared with rats treated with insulin or
      MA alone. On the contrary, salbutamol, even at the highest dose (15 mg/kg, IP),
      was completely ineffective against 2-DG-induced hyperphagia. The present results
      support the previously proposed notion that there are different neuronal or
      humoral circuits underlying the hyperphagic responses to the metabolic stimuli
      induced by glucoprivation (i.e., 2-DG and insulin administration), and they
      extend our knowledge on the effects of salbutamol on glucoprivic and lipoprivic
      control of feeding.

PMID- 8743604
TI  - Metabolic mapping of the effects of chronic voluntary ethanol consumption in
      rats.
AB  - The 2-[14C]deoxyglucose method was used to examine the effects of chronic,
      voluntary ethanol consumption on rates of local cerebral glucose utilization
      (LCGU). LCGU was measured in male Long-Evans rats immediately following the
      completion of a 60-min schedule-induced polydipsia drinking session. Three groups
      of animals were examined: animals with a history of ethanol consumption that
      received ethanol on the test day (ethanol-ethanol), animals with a similar
      ethanol history that were presented with water on the test day (ethanol-water),
      and a control group that received water throughout the experiment (water-water).
      Ethanol consumption on the test day resulted in a highly discrete pattern of
      metabolic changes, with significant decreases in glucose utilization in the
      hippocampal complex, habenula, anterior ventral thalamus, and mammillary bodies,
      whereas increases were observed in the nucleus accumbens and locus coeruleus.
      Rates of LCGU in the ethanol-water group were increased throughout all regions of
      the central nervous system examined, indicating that the long-term consumption of
      moderate ethanol doses that do not produce physical dependence can cause
      significant changes in functional brain activity.

PMID- 8743605
TI  - Effects of antimuscarinic antiparkinsonian drugs on brightness discrimination
      performance in rats.
AB  - Biperiden (BPR) and trihexyphenidyl (THP), the current antimuscarinic drugs of
      choice in the management of parkinsonism, have been shown to exert anticonvulsant
      effects induced by poisoning by the organophosphorus compound soman. The present
      study was undertaken to evaluate the effects of these drugs on performance of a
      simple light-intensity discrimination task in rats under a tandem schedule of
      fixed-ratio (FR) reward/ differential-reinforcement-of-low-rate (DRL) nonreward
      contingencies, for water reinforcement in 2-h experimental sessions. Both BPR
      (0.125-2.0 mg/kg, SC) and THP (0.25-8.0 mg/kg, SC) in general decreased overall
      reinforcement rates in a similar dose dependent and parallel manner, concurrent
      with increased overall nonreinforced responses in an inverted U-shaped dose
      response relationship. Lower doses of BPR (0.125-0.5 mg/kg) and and THP (0.25-2.0
      mg/kg) produced a moderate reduction in reinforcement (> or = 50% of baseline
      controls), which was correlated well with increases in nonreinforced responses
      emitted, whereas, higher doses of BPR (> 0.5 mg/kg) and TPH (> or = 2.0 mg/kg)
      markedly decreased reinforcements, which mainly resulted from the pausing of
      responding in the presence of stereotyped behavior. The behavioral disruption
      induced by BPR was much more rapid than that induced by THP. The ED50 values (0.6
      mg/kg vs. 1.3 mg/kg, respectively) and parallel dose-effect curves suggest that
      these drugs have similar efficacy, and that BPR is about twice as potent as THP,
      a ranking that corresponds with their binding affinity at M-1 muscarinic
      acetylcholine receptors in rat cerebral cortex. Based on the similarity between
      the anticonvulsant doses of these drugs and the maximal doses that in this study
      did not disrupt operant responses (0.125 mg/kg vs. 0.25 mg/kg, respectively), it
      is suggested that both drugs may be useful in protection against seizures
      produced by the cholinesterase inhibitor soman. Overall, these results suggest
      that this multiple schedule operant contingency may have promise as a behavioral
      model to identify the therapeutic or toxic potentials of centrally acting
      antimuscarinic antiparkinsonian drugs based on their congnitive side effects.

PMID- 8743606
TI  - Effects of N omega-nitro-L-arginine methyl ester on benzodiazepine binding in
      some limbic areas of hyperlipidaemic rats.
AB  - Quantitative autoradiography techniques were used to evaluate the chronic effects
      of the potent nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl
      ester, on the binding pattern of [3H]flunitrazepam (benzodiazepine agonist) in
      some behaviorally key limbic areas of the genetic hyperlipidaemic Pittsburg
      Yoshida rat. Administration of this potent synthase inhibitor was capable of
      supplying higher and moderately higher binding levels in the basolateral amygdala
      nucleus (+52%) and in the oriens-pyramidalis CA1 hippocampus layer (+38%),
      respectively. When we tested for the binding changes in the presence of GABA
      (principal benzodiazepine modulator) we noticed that a physiological
      concentration (20 microM) of this inhibitory neurotransmitter was sufficient to
      induce notable changes in other limbic areas. In fact, lower binding values (
      65%) were reported for the bed nucleus of stria terminalis whereas moderately
      higher values (+38%) were obtained for the radiatum-lacunosum molecular CA1
      hippocampus layer. From the saturation studies, it was possible to observe that
      the major receptor variations provoked by the potent synthase inhibitor were not
      only due to changes in the total number of binding sites because there were
      variations, as in the case of the basolateral amygdala nucleus, that were instead
      due to differences in the affinity binding state. These results provide evidences
      of a GABAergic-nitric oxide synthase inhibitor interaction that might also be
      involved in the regulation of convulsive, anxiolytic, and aggressive behaviors
      that are modulated at the benzodiazepine site.

PMID- 8743607
TI  - Dopamine D1/D2 antagonist combinations as antagonists of the discriminative
      stimulus effects of cocaine.
AB  - Although data suggest that the dopaminergic system mediates the discriminative
      stimulus effects of cocaine, neither selective D1 or D2 dopamine agonists nor
      selective D1 or D2 antagonists substitute reliably for or consistently block
      these effects. These findings suggest that concurrent activity at these receptor
      subtypes may underlie this discrimination. Accordingly, it would be expected that
      simultaneous blockade of these receptors may be necessary to block it fully. The
      ability of various combinations of the D1 antagonist, SCH 23,390, and the D2
      antagonist, haloperidol, were tested for their ability to block the cocaine
      stimulus in rats trained to discriminate cocaine (7.5, 10, or 13 mg/kg) from
      vehicle. Antagonist combinations decreased the percentage of cocaine-appropriate
      responses 10-95% below the cocaine baseline at doses of the antagonist that were
      inactive when given separately. These findings support the position that activity
      at D1-like and D2-like receptor subtypes may account for more of the
      pharmacological action of cocaine than activation of a single dopamine receptor
      subtype.

PMID- 8743608
TI  - Regional brain patterns of dopamine, metabolites and D2 receptors in memory.
AB  - Patterns of dopamine (DA), 3,4-dihydroxyphenyl acetic (DOPAC), and homovanillic
      (HVA) acids, para-tyramine (p-TA), and D2 receptors for eleven structures of
      forebrain and midbrain were examined at 1 and 6 days after one trial passive
      avoidance training of rats, at 1 day after "psychogenic" amnesia production,
      immediately following training, and at the last day after foot shock of rats with
      previous "psychogenic" amnesia administration. Essential dopaminergic differences
      have been found between the groups studied. More significant neurochemical
      changes were observed in rats from trained and retrieval training groups.
      Regional DA changes were accompanied by a diminution of DA metabolism, an
      increase of D2 receptor density and p-TA. These neurochemical alterations
      differentially characterized the regional neurochemical patterns found in rat's
      exhibition nonretention (trained), forgetting, and amnesia. It is suggested that
      the present data reflect the existence of quantitative relationships between D2
      receptors, DA, and p-TA, which are probably important in modulation of memory.

PMID- 8743609
TI  - Naloxone-precipitated changes in biogenic amines and their metabolites in various
      brain regions of butorphanol-dependent rats.
AB  - Influence of a naloxone (an opioid receptor antagonist) challenge (5 mg/kg, IP)
      on levels of biogenic amines and their metabolites in various brain regions of
      rats infused continuously with butorphanol (a mu/delta/kappa mixed opioid
      receptor agonist; 26 nmol/microliter/h) or morphine (a mu-opioid receptor
      agonist; 26 nmol/microliter/h) was investigated using high-performance liquid
      chromatography with electrochemical detection (HPLC-ED). Naloxone precipitated a
      withdrawal syndrome and decreased the levels of: dopamine (DA) in the cortex and
      striatum, 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum, homovanilic
      acid (HVA) in the striatum, limbic, midbrain, and pons/medulla regions in
      butorphanol-dependent rats. However, the levels of norepinephrine (NE), serotonin
      (5-hydroxytryptamine; 5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the
      regions studied were not affected by naloxone-precipitated withdrawal. In
      addition, naloxone increased the HVA/DA ratio in the cortex, while this ratio was
      reduced in the limbic, midbrain, and pons/medulla. The reduction of 5-HIAA/5-HT
      ratio was also detected in the limbic area. In the animals rendered dependent on
      morphine, the results obtained were similar to those of butorphanol-dependent
      rats except for changes of 5-HIAA levels in some brain regions. These results
      suggest that an alteration of dopaminergic neuron activity following a reduction
      of DA and its metabolites in specific brain regions (e.g., striatum, limbic,
      midbrain, and pons/medulla) play an important role in the expression of the
      opioid withdrawal syndrome.

PMID- 8743610
TI  - Comparison of the effects of prototypical behavioral stimulants on locomotor
      activity and rotational behavior in rats.
AB  - The present study was performed to characterize on rotational behavior the dose-
      and time-effect relationship of four prototypical behavioral stimulants that
      interact with dopamine systems via different mechanisms of action. Drug effects
      on rotational behavior was compared with effects on locomotor activity. The drugs
      examined were apomorphine (0.03-1.0 mg/kg), d-amphetamine (0.1-3.0 mg/kg),
      cocaine (3.0-56 mg/kg), and caffeine (10-100 mg/kg). SKF-38393 (0.3-10 mg/kg), a
      dopamine receptor agonist that has only modest effects on locomotor activity, was
      tested as a comparison. In rats with unilateral 6-hydroxydopamine (6-OHDA)
      induced lesions of the nigrostriatal tract, d-amphetamine and cocaine dose
      dependently increased both the duration and the maximum number of turns/10 min,
      whereas apomorphine and caffeine increased only the duration of turning. There
      was a significant correlation of the effects of the four drugs on rotational
      behavior with effects on locomotor activity, but effects across drugs were not
      identical. Dose-response curves revealed potency differences among drugs in their
      effects on the two behaviors (e.g., apomorphine stimulated rotational behavior at
      a lower dose than it stimulated locomotor activity, whereas the converse was true
      with caffeine). Different mechanisms of action of these drugs might account for
      the differences in their effects on these behaviors.

PMID- 8743611
TI  - Development of an affordable hi-resolution activity monitor system for laboratory
      animals.
AB  - We describe a hardware and software system for recording and analyzing the
      spatial and temporal pattern of locomotor activity of laboratory animals. The
      system offers maximal spatial resolution 500-fold greater than existing light
      beam monitors. An infrared motion analysis systems (MacReflex, Qualysis)
      simultaneously tracks the location of up to 20 subjects (identified by reflective
      markers) to within 0.04 mm at a rate of up to 50 Hz. Macintosh software provides
      measures of distance traveled, amount of area traversed, number of position
      changes (microevents), average time between movements, number of left and right
      turns, number of forward movements and reversals, as well as temporal and spatial
      scaling exponents. This system was validated by comparing these parameters to
      direct observer scoring of video tapes and other commercially available activity
      monitors. Our findings show that applying reflective markers to the subjects does
      not significantly alter activity levels. The effect of pharmacological
      manipulation with d-amphetamine is provided to show the value of the different
      activity parameters. The main advantages of this system are very high spatial
      resolution, capacity to monitoring up to 20 animals simultaneously at reasonable
      cost, and lack of sensitivity of the system to ambient lighting. The main
      limitation is the need to apply reflective markers.

PMID- 8743612
TI  - Acute and chronic effects of morphine in pigeons responding under a progressive
      ratio schedule of food delivery.
AB  - Although progressive-ratio schedules have often been used by behavioral
      pharmacologists to index the relative reinforcing effects of drugs of abuse, they
      have been ignored in the study of tolerance to opioids. The present study
      examined tolerance to morphine in pigeons responding under a progressive-ratio 5
      schedule of food delivery. Acute administrations of morphine produced general
      dose-dependent reductions in response rates and breaking points. Dose-response
      curves for both measures shifted rightward substantially (roughly fivefold)
      following chronic (daily) exposure to morphine, indicating that tolerance
      developed to the drug's effects.

PMID- 8743613
TI  - Cocaethylene-induced kindling of seizure effects: cross-specificity with cocaine.
AB  - Sensitization and cross-sensitization to the seizurogenic effects of cocaine and
      cocaethylene were examined in the HS strain of mice. Animals were administered IP
      injections of either 48 mg/kg cocaine or 32 mg/kg cocaethylene once per day for 4
      days. On the fifth day, mice were injected with either the same drug that was
      administered on days 1-4 or the alternative psychostimulant and the occurrence of
      seizure activity was recorded. Repeated cocaine administration resulted in the
      induction of tonic-clonic seizures and status epilepticus in 90% of the animals
      tested with cocaine on the fifth day. A similar increase in seizure prevalence,
      noted as a kindling effect, was observed in cocaethylene-treated animals tested
      with cocaethylene in that 90% of the mice exhibited status epilepticus on the
      last test day. Significant cross-sensitization was observed only in the group
      that received cocaethylene following repeated cocaine exposure. However, data
      obtained from animals injected with cocaine following cocaethylene treatment also
      were suggestive of cross-sensitization effects. Results are discussed in terms of
      the potential mechanistic differences between cocaine and its ethanol-derived
      product, as well as its relevance to cocaine use/abuse.

PMID- 8743614
TI  - Differential sensitivity of mice bred for stress-induced analgesia to morphine
      and ACEA-1011 in the formalin test.
AB  - The antinociceptive effect of morphine, an opioid receptor agonist, and ACEA
      1011, a novel NMDA receptor/glycine site antagonist, was examined in the formalin
      test in mice selectively bred for high (HA) and low (LA) swim stress-induced
      analgesia (SSIA). A subcutaneous (SC) injection of formalin produced a biphasic
      nociceptive response in both lines. HA mice spent more time licking the injected
      paw than the LA mice in both phases of the formalin test. Morphine was equally
      potent in the early phase in both lines, but it was more potent in HA mice than
      in LA mice in the tonic late phase of the formalin test. Similarly, ACEA-1011
      produced an equally potent antinociceptive effect in the early phase in both
      lines; however, the compound was more potent in LA mice than in HA mice in the
      tonic late phase of the formalin test. These data suggest that in HA mice
      antinociception in the tonic late phase of the formalin test is mediated largely
      by an opioid-mediated mechanism, whereas in the opioid-deficient LA line at least
      a nonopioid-mediated mechanism involving the NMDA receptor is also implicated.

PMID- 8743615
TI  - Lack of acute tolerance development to the subjective, cognitive, and psychomotor
      effects of nitrous oxide in healthy volunteers.
AB  - A crossover, double-blind trial was conducted using eleven healthy volunteers to
      determine whether and the degree to which acute drug tolerance occurred to the
      subjective, cognitive, and psychomotor effects of a range of subanesthetic
      nitrous oxide doses (0, 10, 20, 30, and 40%). There was little evidence of acute
      drug tolerance to the subjective measures or to the cognitive/psychomotor
      impairing effects of nitrous oxide at any of the concentrations tested over the
      course of the 120-min inhalation.

PMID- 8743616
TI  - Preclinical profile of the mixed 5-HT1A/5-HT2A receptor antagonist S 21,357.
AB  - This study evaluated the pharmacological and behavioral effects of S 21,357, a
      drug with high affinity for both 5-HT1A and 5-HT2A receptors. The drug behaved as
      antagonist at both 5-HT1A autoreceptors and postsynaptic 5-HT1A receptors, as it
      prevented the inhibitory effect of lesopitron on the electrical discharge of the
      dorsal raphe nucleus (DRN) 5-HT neurons and the activity of forskolin-stimulated
      adenylate cyclase in hippocampal homogenates. In addition, S 21,357 (4 and 128
      mg/kg, PO) inhibited 5-HTP-induced head-twitch responses in mice, indicating that
      it possesses 5-HT2A antagonistic properties. In a test battery designed to assess
      defensive behaviors of Swiss-Webster mice to the presence of, or situations
      associated with, a natural threat stimulus (i.e., rat), S 21,357 (0.12-2 mg/kg,
      IP) reduced contextual defense reactions after the rat was removed, risk
      assessment activities when the subject was chased, and finally, defensive attack
      behavior. These behavioral changes are consistent with fear/anxiety reduction.
      Furthermore, the drug strongly reduced flight reactions in response to the
      approaching rat. This last finding, taken together with recent results with panic
      modulating drugs, suggest that S 21,357 may have potential efficacy against panic
      attack. Finally, our results suggest that compounds sharing high affinities for
      both 5-HT1A and 5-HT2A receptors may directly or synergistically increase the
      range of defensive behaviors affected.

PMID- 8743617
TI  - Discriminative stimulus effects of dopaminergic agents in rhesus monkeys.
AB  - Recent reports have shown that treatment with dopamine reuptake inhibitors can
      selectively decrease responding maintained by low doses of cocaine in rhesus
      monkeys. This may occur because response-independent delivery of a reuptake
      inhibitor and response-dependent cocaine have common effects. One behavioral
      effect that dopamine reuptake inhibitors and cocaine share is their ability to
      serve as a discriminative stimulus. To compare discriminative effects of several
      dopaminergic agents with their ability to attenuate cocaine-maintained
      responding, three rhesus monkeys were first trained to discriminate intravenous
      injections of cocaine (0.1 mg/kg) from saline. Following generalization testing
      with various doses of cocaine (0.001-1.0 mg/kg), the relative potencies of
      phentermine (0.03-1.0 mg/kg), d-amphetamine (0.01-1.0 mg/kg), GBR 12,909 (0.01
      1.0 mg/kg), and buspirone (0.03-0.56 mg/kg) to substitute for cocaine were
      assessed. Each drug except buspirone resulted in predominantly cocaine
      appropriate responding at doses that were generally without rate-decreasing
      effect. The ED50 for the ability of these drugs to substitute for cocaine
      exhibited the same rank order as that for their effectiveness in decreasing
      cocaine-maintained responding. Thus, the current results show that the potencies
      of dopaminergic drugs to decrease cocaine-maintained responding and substitute
      for cocaine in a drug discrimination paradigm are related.

PMID- 8743618
TI  - Neurotensin levels and receptors in HAS and LAS rat brains: effects of ethanol.
AB  - Previous studies of neurotensin (NT) levels and NT receptor densities in specific
      brain regions of mice selectively bred for differences in sensitivity to ethanol
      have shown that NTergic processes may mediate some actions of ethanol. In the
      present study, we have determined the levels of NT and NT receptor densities in
      specific brain regions of HAS and LAS rats that have been selectively bred for
      differences in sensitivity to ethanol-induced loss of righting response. Regional
      differences in NT levels were observed in brains from both HAS and LAS rats and
      values in hypothalamus, ventral midbrain, and nucleus accumbens from female rats
      were 25 to 75% higher than levels in corresponding regions from male rats.
      However, there were no significant line differences in NT-ir levels in
      corresponding regions from HAS and LAS animals. High-affinity binding (NTH Bmax
      values), measured by Scatchard analyses, were higher in ventral midbrain from HAS
      males than from LAS males. NTH receptor densities were higher in HAS males than
      in HAS females; sex differences were not observed in the LAS line. There were no
      significant line or sex differences between HAS and LAS in low-affinity (NTL)
      Bmax values in any brain region. In HAS females, subhypnotic doses of ethanol
      produced a decrease in NT levels in nucleus accumbens, whereas, hypnotic doses
      caused an increase in NT levels. Likewise, hypnotic doses elicited increases in
      NT levels in hypothalamus of female HAS and LAS, but not in ventral midbrain or
      caudate putamen. These results are consistent with low dose activation of
      mesolimbic and nigrostriatal dopaminergic neurons in which NT is colocalized with
      dopamine and with high dose inhibition of these pathways.

PMID- 8743619
TI  - Resolving the sexual intimacy paradox: a developmental model for the treatment of
      sexual desire disorders.
AB  - Although relationship factors are an important component in the evaluation and
      treatment of hypoactive sexual desire (HSD) disorders, a sexual intimacy paradox
      often occurs wherein many couples increase the intimacy in their relationship
      while their sexual desire continues to decline. To resolve the apparent paradox
      and to further our understanding of the relationship between intimacy and
      eroticism, we offer a developmental model of sexual intimacy as a guide to
      treating the interpersonal aspects of HSD and other sexual dysfunctions. This
      model expands Erikson's developmental phase of intimacy into five elements:
      conflagration, merger, fusion, differentiation, and integration. The model is
      described and case examples are presented as illustrations of the therapeutic
      issues and resolutions within each element.

PMID- 8743620
TI  - Antidepressants in the treatment of premature ejaculation.
AB  - The SSRI antidepressants have emerged as effective new treatment for patients
      with premature ejaculation whether or not these patients suffer from depression.
      Clomipramine, fluoxetine, paroxetine, and sertraline seem to be a safe treatment
      option for patients with premature ejaculation, especially in cases of failed
      psychological treatment, in rejection of psychological treatment, and when
      partners are unwilling to cooperate in treatment. Further controlled and larger
      studies that focus on clinically relevant issues such as dose, length of
      treatment, maintenance of beneficial effects after treatment discontinuation, and
      the combination of pharmaco- and behavior therapy for premature ejaculation are
      warranted. Other medications, such as benzodiazepines, may be useful in some
      cases of premature ejaculation.

PMID- 8743621
TI  - Prostitution advertisements suggest association of transvestism and masochism.
AB  - Previous research and clinical observation have suggested that the sexual
      interest of many transvestites include involvement in sadomasochistic sexual
      acts. Through data gathered via prostitution advertisements in print media, we
      tested the hypothesis that prostitutes welcoming cross-dressing client would be
      primarily those describing themselves as dominant. The specialty of the
      prostitute was recorded by coding the advertisements for the presence or absence
      of the features of dominance, submissiveness, acceptance of cross-dressing
      clients, and whether the prostitute was a biological male presenting as a woman
      or quasi-woman. The findings showed that 20% of prostitutes describing themselves
      as dominant welcomed cross-dressing clients, whereas none of the other subgroups
      of prostitutes mentioned cross-dressing clients in their advertisements. These
      findings reinforce other lines of indirect evidence suggesting that, in
      heterosexual men, the presence of masochism increases the likelihood of
      transvestism, and vice versa.

PMID- 8743622
TI  - The effect of condoms in sexually explicit narratives on male sexual arousal.
AB  - Research into why people choose not to use condoms despite a growing AIDS
      epidemic has tapped the attitude that the use of condoms somehow interferes with
      the progression of the sexual act or lessens sexual pleasure. The current study
      investigated the effects on male sexual arousal of condom use described in
      sexually explicit audiotaped narratives. The sexual arousal of 14 male university
      students was measured physiologically by penile plethysmography and by self
      report using a within-subjects design. Subjects listened to 10 audiotaped
      scripts, half of which included the use of a condom and half of which did not. No
      significant differences in either physiological or subjective arousal data were
      found between conditions.

PMID- 8743623
TI  - Beliefs about the state, goals, and objects of sexual desire.
AB  - Little is known about how men women conceptualize sexual desire. This descriptive
      study explored beliefs about the nature of sexual desire. Participants defined
      sexual desire in a free response format. The results suggest that there is no
      single common understanding of sexual desire. In particular, although men and
      women conceptualize the state of sexual desire in a manner similar to researchers
      and theorists (i.e., as a subjective, psychological experience rather than as a
      physiological or behavioral sexual event), sexual desire represents a more
      romantic, interpersonal experience for women than for men. Significantly more
      women than men believed that love and emotional intimacy are important goals of
      sexual desire, and fewer women than men viewed sexual activity as a goal of
      sexual desire.

PMID- 8743625
TI  - Survey report: concept of penis size.

PMID- 8743626
TI  - Detailed investigations of 5-HT3 compounds in a drug discrimination model.
AB  - Serotonin type-3 (5-HT3) receptors modulate both dopamine (DA) release and
      locomotor stimulation induced by cocaine, yet appear to be ineffective at
      blocking its stimulus and reinforcing effects. To more thoroughly characterize a
      potential modulatory role of 5-HT3 receptors in the stimulus effects of cocaine,
      rats (n = 8/group) were trained to discriminate cocaine (10 mg/kg, IP) or the 5
      HT3 agonist 1-(meta-chlorophenyl)-biguanide (mCPBG: 15 mg/kg, IP) from saline
      using a standard drug discrimination task. In rats trained to discriminate
      cocaine, mCPBG (2.5-20 mg/kg) produced, at best, a partial substitution while
      mCPBG (10 mg/kg) did not alter the cocaine dose-response relationship. The 5-HT3
      antagonists MDL 72222 (10 mg/kg) and ondansetron (1.25-16 mg/kg) did not
      attenuate the cocaine cue. In rats trained to discriminate mCPBG from saline, the
      5-HT precursor l-5-hydroxytryptophan (12.5-50 mg/kg) dose-dependently substituted
      for mCPBG, whereas the 5-HT3 antagonist zacopride (0.1-10 mg/kg) partially
      antagonized the mCPBG cue, demonstrating that mCPBG produces distinct
      discriminable effects that appear to be mediated by 5-HT, possibly 5-HT3,
      receptors. However, cocaine (5-20 mg/kg) did not substitute in mCPBG-trained
      rats. Overall, these data support previous findings to suggest that 5-HT3
      receptors play little role in mediating the discriminative stimulus effects of
      cocaine and suggest that the neurochemical mechanisms and/or sites of action
      important for the generation of the discriminative stimulus vs. locomotor
      stimulatory effects of cocaine may be dissociable.

PMID- 8743627
TI  - Effects of ethanol in a putative rodent model of tardive dyskinesia.
AB  - The effects of acute challenge with ethanol were studied in a putative rodent
      model of tardive dyskinesia. Chronic administration of fluphenazine elicited
      vacuous chewing movements (VCMs) in the rat. Neuroleptic-induced VCMs were dose
      dependently suppressed by ethanol in a behaviorally specific fashion. Suppression
      by ethanol of neuroleptic-induced VCMs was reversed by pretreatment with the
      benzodiazepine inverse agonist Ro 15-4513 (2.5 mg/kg). These findings suggest
      that ethanol may acutely suppress neuroleptic-induced dyskinesias in humans via
      stimulation of GABAA receptors and are compatible with the previously reported
      clinical effects of alcohol consumption on the extrapyramidal system. Treatment
      strategies focussed on GABAergic stimulation deserve further investigation in the
      management of tardive dyskinesia.

PMID- 8743628
TI  - Orally delivered methadone as a reinforcer for rhesus monkeys: the relationship
      between drug concentration and choice.
AB  - The relative reinforcing effects of orally delivered methadone were studied in
      five male rhesus monkeys. Drug deliveries were available under either a fixed
      ratio (FR) or a fixed-interval (FI) schedule. Three concentrations of methadone,
      low (0.05 mg/ml), intermediate (0.2 mg/ml), and high (0.8 mg/ml) were delivered
      in 0.65 ml volumes. In the first experiment, monkeys were presented with a choice
      paradigm. Under independent FR schedules responding led to a delivery of either a
      methadone solution or the water vehicle. For each concentration, deliveries of a
      methadone solution maintained higher response rates than did deliveries of water.
      In the second experiment, methadone concentrations were tested in pairs in the
      following sequence: high vs. low, high vs. intermediate, intermediate vs. low,
      high vs. intermediate (retest), and high vs. low (retest). The retest of the last
      two pairs was designed to counterbalance the test sequence, so that order
      effects, if they existed, could be detected. Regardless of the schedule, the
      higher concentration of the methadone pair maintained a greater response rate
      than did the lower concentration. The present results are consistent with the
      generalization based on other studies that over a broad range of concentrations
      and across pharmacological classes, reinforcement schedules, and routes of
      administration, reinforcing effects increase with increases in drug
      concentration.

PMID- 8743629
TI  - Ethanol effect on activation and maintenance of cold stress response in immature
      rats.
AB  - Rats at thermoneutral ambient temperature (Ta) exhibit change in thermoregulatory
      response to ethanol (EtOH) from 2 to 15 days of age. In the present study, rats
      at 2-3, 8-9, and 14-15 days of age were administered either saline or EtOH (4
      g/kg b.wt.;IP) using two different routines to determine EtOH effect on specific
      cold defense mechanisms. Injection of EtOH in the first routine occurred after
      exposure to cold Ta, to determine effect on maintenance of cold thermogenesis.
      EtOH-induced metabolic depression increased from 3 to 8 days of age, with little
      change after this time. Injection of EtOH in the second routine was at
      thermoneutral Ta, followed at 20 min postinjection by rapid exposure to cold Ta
      to determine effect on activation of cold thermogenesis. EtOH-treatment delayed
      onset of cold thermogenesis at 2-3 and 14-15 days of age, and completely
      eliminated 8-9-day-old response to cold Ta. Rats exposed to cold Ta at 2-3 days
      of age exhibited a slower rate of EtOH absorption and lower blood EtOH
      concentration than rats in the older groups, to explain some age differences in
      EtOH response.

PMID- 8743630
TI  - Role of dopaminergic mechanisms in the stimulatory effects of MK-801 injected
      into the ventral tegmental area and the nucleus accumbens.
AB  - The bilateral administration of 10 micrograms of (+)MK-801, but not (-)MK-801,
      into either the VTA or the N.Ac. stimulated locomotor activity. The stimulation
      induced by (+)MK-801 at both sites was inhibited by reserpine (5 mg/kg, SC) and
      the D1 antagonist, SCH 23390 (0.1 mg/kg, SC). Eticlopride (0.03 mg/kg, SC), a D2
      antagonist, inhibited the stimulation produced by MK-801 in the VTA but not in
      the N.Ac. Baclofen (32 ng), a GABAB receptor agonist, injected into the VTA
      inhibited the stimulatory response to MK-801 injected systemically, into the VTA,
      or into the N.Ac., but did not significantly inhibit spontaneous locomotion or
      the stimulatory response to apomorphine (5 mg/kg, SC). These observations suggest
      that the stimulatory effects of MK-801 in the VTA and the N.Ac. are dependent on
      endogenous dopamine. In addition, the effects produced by MK-801 injected into
      the VTA closely resemble those produced by the systemic administration of low
      doses of MK-801, suggesting that this is the primary site of action of MK-801.

PMID- 8743631
TI  - Unsignaled morphine delivery does not disrupt the development of associative
      morphine tolerance in the rat.
AB  - When morphine administration is paired with a distinctive context, tolerance to
      morphine's analgesic effects comes readily under the associative control of the
      drug-paired context. These associative tolerance effects are eliminated when a
      relatively short (i.e., 6 h) interdose interval (IDI) is used for conditioning.
      Contemporary models of learned tolerance explain the absence of learning at short
      IDIs by positing that residual morphine effects from a recent drug exposure
      disrupt the formation of drug-context associations. The present studies examined
      the impact of unsignaled morphine injections given 6 h prior to drug-context
      pairings on the development of associative tolerance. Analgesia was measured by
      the tail-flick method, and tolerance levels were assessed by dose-response curve
      methodology. Morphine preexposure had no detectable influence on the acquisition
      of associative tolerance when rats were tested immediately after conditioning,
      after a 30-day rest interval, or after a 30-day period of daily saline injections
      in their home-cage environment. These data suggest disruption of associative
      tolerance effects at short IDIs is not attributable to residual effects of
      morphine from the immediately preceding trial.

PMID- 8743632
TI  - Nicotine abstinence syndrome precipitated by an analog of neuropeptide FF.
AB  - In a recently introduced rodent model of nicotine abstinence syndrome the
      observed behavioral signs closely resembled those typical of rat opiate
      abstinence syndrome. Nicotine-induced release of endogenous opioids may
      contribute to nicotine dependence; morphine potently reverses nicotine abstinence
      signs, while naloxone precipitates abstinence signs and prevents nicotine from
      alleviating them. Considerable evidence suggests that neuropeptide FF, an
      endogenous antiopiate peptide, contributes to opiate dependence. Third ventricle
      injection of neuropeptide FF precipitates abstinence syndrome in morphine
      dependent rats, as does SC injection of its lipophilic analogs, dansyl-PQRFamide
      and dansyl-RFamide. Might NPFF also play a role in nicotine dependence? In the
      present study, SC injection of 15 or 25 mg/kg dansyl-RFamide or vehicle alone
      dose dependently precipitated an abstinence syndrome in nicotine-dependent rats.
      There was a significant, p < 0.01, positive linear trend of abstinence signs as a
      function of dose. Categories of abstinence signs had the same rank ordering by
      frequency as observed in spontaneous nicotine abstinence. Injection of 25 mg/kg
      dansyl-RFamide SC had no significant effect in nondependent rats.

PMID- 8743633
TI  - Changes in sensitivity to nicotine and brain nicotinic receptors following
      chronic nicotine and corticosterone treatments in mice.
AB  - Chronic nicotine treatment often results in tolerance to nicotine as well as
      increases in brain [3H]-nicotine binding and [125l]-alpha-bungarotoxin (alpha
      BTX) binding. Chronic corticosterone (CCS) treatment also produces tolerance to
      nicotine, but it does not change [3H]-nicotine binding; decreases in alpha-BTX
      binding are observed, which suggests that tolerance to nicotine may be related to
      decreases in the number of this nicotinic receptor subtype. In the studies
      reported here, C57BL/6 mice were implanted subcutaneously with cholesterol or 60%
      CCS/40% cholesterol-containing pellets and were infused continuously with saline
      (control) or nicotine for a total of 9 days. Effects of acute nicotine challenge
      on Y-maze crossing and rearing activities, heart rate, and body temperature were
      measured. Both chronic nicotine and CCS treatment resulted in tolerance to
      nicotine for all of the measures, and some evidence for additivity was seen in
      the animals that were cotreated with CCS and nicotine. Chronic nicotine infusion
      increased brain nicotine binding and CCS treatment reduced alpha-BTX binding.
      Decreases in alpha-BTX binding were not detected in the cotreated animals. The
      latter finding argues that changes in alpha-BTX binding are not reliable
      predictors of or a cause of tolerance to nicotine.

PMID- 8743634
TI  - Effect of amphetamine on behavior maintained by sucrose: interaction of
      reinforcement schedule and food restriction.
AB  - A multiple schedule (Mult FR 10 VI 30") was employed to examine the interaction
      of reinforcement schedule and food restriction on amphetamine's effects on lever
      pressing behavior. High response rates were observed in fixed ratio (FR) 10
      components. Significantly lower response rates were observed under the variable
      interval (VI) 30" schedule. In the nonrestricted feeding condition, significant
      decreases in high rate FR 10 responding occurred after administration of 1.0
      mg/kg amphetamine while lower rates under the same schedule were increased by
      0.30 and 1.0 mg/kg amphetamine. In contrast, VI 30" responding was minimally
      effected at any amphetamine dose. Food restriction resulted in significant
      increases in responding in both schedule components. Under food restriction,
      significant decreases in responding were observed only in the FR 10 components at
      the highest amphetamine dose. The data indicate that amphetamine produced rate
      convergent effects and the susceptibility of the animal to these effects was
      dependent on the schedule of reinforcement and food restriction.

PMID- 8743635
TI  - Differential sexual activity of isolated and group-housed male mice: influence of
      acute d-amphetamine sulfate administration.
AB  - It is established that group housing can impair sexual activity of male mice, and
      that central catecholamines are involved in male sexual response, but it is not
      known whether catecholamine mechanisms are involved in sexual impairment in
      grouped males. Injections of 0, 0.22, 0.67, 2.0, or 6.0 mg/kg of d-amphetamine
      sulfate were administered 1 h before testing to individually and group-housed
      male C57BL/6J mice. Isolated mice showed more mounts, intromissions, and
      ejaculations and shorter response latencies than did group-housed mice. The
      latencies to first mount, intromission, and ejaculation were nonmonotonically
      related to dosage, being shortest at the lowest dosage in isolated mice, but
      significantly elevated by the higher dosages in both isolated and grouped males.
      The number of ejaculations was significantly elevated by moderate dosages in both
      isolated and grouped mice, peaking at the 2.0 mg/kg dosage in isolated mice and
      at 0.67 mg/kg in grouped mice. Nevertheless, amphetamine treatment generally
      failed to eliminate differences between males from isolated and grouped
      backgrounds.

PMID- 8743636
TI  - Dose-dependent decrements in adult male rat sexual behavior after neonatal
      clorimipramine treatment.
AB  - Previous studies found that months after clorimipramine (CLI) treatment of male
      neonatal rats, the mature animals developed behavioral deficits and REM sleep
      abnormalities that modeled human endogenous depression. In the initial studies
      neonatal rats received CLI 30 mg/kg/IP daily from age 8 through 21 days.
      Diminished sexual activity of the adult rats treated neonatally in this manner
      was a behavioral deficit that supported the depression model. However, in
      subsequent studies in our laboratory, the same neonatal treatment occasionally
      failed to produce adult sexual deficiencies found in the initial studies. The
      inconsistency raised the possibility that neonatal CLI treatment was not a
      reliable method to produce an animal model of depression. An alternative
      hypothesis was that the CLI dose was too low. The present study tested this
      hypothesis. Placebo or one of four CLI doses was administered daily to male
      neonatal rats (n = 12/treatment group) from age 8 days through 21 days: 30 (the
      original dose), 40, 50, and 60 mg/kg/IP. Six components of adult sexual behavior
      were measured at age 5 months. Deficiency of each sexual behavior was found to be
      dose-dependent (r = 0.5, p < 0.001). The 30 mg/kg/day dose caused deficiencies in
      some, but not all, sexual behavior measures. Higher doses caused deficiencies in
      all measures of sexual behavior. The results support the hypothesis that neonatal
      CLI treatment at doses higher than the original 30 mg/kg/day caused reliable
      impairments in adult male rat sexual behavior, and therby support the reliability
      of neonatal CLI treatment to produce an animal model of endogenous depression.

PMID- 8743637
TI  - Inhibitors of protein and RNA synthesis block context memory and long-term
      habituation in the crab Chasmagnathus.
AB  - The crab Chasmagnathus granulatus reacts to a shadow passing overhead (a danger
      stimulus) with an escape response that habituates quickly and for at least 5
      days. Recently, it has been reported that cycloheximide (CY) disrupts this long
      term habituation and the corresponding context memory. In the present article,
      experiments with CY and an inhibitor of RNA synthesis, actinomycin-D (ACT), were
      parallelly conducted. An injection of CY (20 micrograms) or ACT (0.62 microgram)
      reduced the incorporation of [14C]-aminoacid into cerebral plus thoracic ganglia
      by 80% for 2 h and 59.7% for 1 h, respectively, but no inhibition was found at 24
      h. Both ACT (0.62 microgram) and CY (20 micrograms) administered immediately
      after training (15 trials with the danger stimulus) impaired either long-term
      habituation or context memory when tested at 24 h. Because ACT and CY have in
      common only their direct or indirect inhibitory effect on protein synthesis, this
      finding is considered as an additional evidence that long-term memory in
      Chasmagnathus requires de novo protein synthesis. However, pretraining ACT or CY
      impaired context memory at 24 h but not long-term habituation. Such a disparity
      is explained by an unspecific attenuating effect upon the response, attributed to
      drug x training interaction. Neither ACT nor CY affected short-term habituation.

PMID- 8743638
TI  - Effects of acute and repeated clozapine injections on cholinomimetic-induced
      vacuous jaw movements.
AB  - Three studies were undertaken to investigate the effects of the atypical
      neuroleptic clozapine on the vacuous jaw movements induced by cholinergic
      stimulation in rats. In the first experiment, acute clozapine injections (4.0
      16.0 mg/kg) produced a dose-related suppression of the vacuous jaw movements
      induced by 0.4 mg/kg physostigmine. In the second experiment, acute injections of
      clozapine (2.0-16.0 mg/kg) also suppressed vacuous jaw movements induced by 4.0
      mg/kg pilocarpine in a dose-related manner. The third experiment was designed to
      compare the effects of acute and repeated administration of 16.0 mg/kg clozapine.
      In this experiment, there were three groups: one that received 4.0 mg/kg
      pilocarpine, a second group that received pilocarpine plus an acute injection of
      16.0 mg/kg clozapine, and a third group that received injections of 16.0 mg/kg
      clozapine for 14 consecutive days, including the final day in which they also
      were injected with pilocarpine. For the third experiment, animals were assessed
      for the sedative effects of clozapine as well as vacuous jaw movements. The
      results indicated that either acute or repeated injections of 16.0 mg/kg
      clozapine reduced vacuous jaw movements relative to rats that received
      pilocarpine alone, and the two clozapine-treated groups did not differ from each
      other. The sedation ratings indicated that acute injections of 16.0 mg/kg
      clozapine produced substantial drowsiness and sedation, whereas rats that had
      received clozapine for 14 days did not show substantial sedation. These results
      indicate that clozapine can suppress cholinomimetic-induced vacuous jaw
      movements. The suppressive effects of clozapine on pilocarpine-induced vacuous
      jaw movements do not show tolerance within the 14-day period of repeated
      injections, whereas the sedative effects of clozapine do show tolerance. Thus,
      these results demonstrate that the suppression of pilocarpine-induced vacuous jaw
      movements by clozapine is not merely an artifact of clozapine-induced sedation.
      Because pilocarpine-induced vacuous jaw movements share some characteristics with
      human parkinsonian symptoms, the present results are consistent with previous
      reports indicating that repeated injections of clozapine produce anti
      parkinsonian effects.

PMID- 8743639
TI  - Type A CCK receptors mediate satiety effects of intestinal nutrients.
AB  - Previous work indicates that endogenous CCK mediates suppression of sham feeding
      by some intraintestinal nutrients. To test whether the mechanism involved is
      dependent upon action at type A or type B CCK receptors, we examined the ability
      of CCKA (devazepide) and CCKB (L-365,260) receptor antagonists to attenuate the
      suppression of sham feeding by intraintestinal oleic acid, maltotriose, or L
      phenylalanine. Suppression by oleic acid or maltotriose was dose dependently
      attenuated by intraperitoneal administration of the CCKA receptor antagonist, as
      was suppression by exogenous CCK. The CCKB receptor antagonist failed to
      attenuate the suppression of sham feeding by these nutrients. Neither receptor
      antagonist attenuated the suppression of sham feeding induced by intraintestinal
      L-phenylalanine. These results suggest that suppression of sham feeding by
      intestinally infused oleic acid and maltotriose is mediated by endogenous CCK
      acting at CCKA receptors.

PMID- 8743640
TI  - Phenobarbital in the anticonvulsant dose range does not impair learning and
      memory or alter brain AChE activity or monoamine levels.
AB  - The learning and memory in adult, male Wistar rats were assessed using the T-maze
      and passive avoidance tests after chronic administration of phenobarbital (PB) at
      5, 15, 30, 60, or 75 mg/kg intraperitoneally (IP) for 21 days. The PB levels in
      plasma, the acetylcholine esterase (AChE) activity in the motor cortex, pyriform
      cortex, olfactory bulb, striatum, septum, and hippocampus and the levels of
      serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA),
      dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) levels in the
      hippocampus were measured. There was no significant change in learning and
      memory, AChE activity, or monoamine levels at plasma PB levels of 1.5, 6.0, 9.0,
      and 25 micrograms/ml (corresponding to doses of 5, 15, 30, or 60 mg/kg PB,
      respectively). However, at a plasma level of 55 micrograms/ml (75 mg/kg), PB
      caused impairment in learning and memory. It was associated with an increase in
      AChE activity and 5-HT levels in the hippocampus. The results indicate that
      chronic PB administration may not be linked to impaired learning and memory
      functions at doses used in anticonvulsant therapy.

PMID- 8743641
TI  - EEG abnormalities before clozapine therapy predict a good clinical response to
      clozapine.
AB  - The purpose of this study was to test the hypothesis that minor EEG abnormalities
      predict a favorable response to clozapine. Eighty-six psychotic clozapine-treated
      psychiatric inpatients with EEG records before starting clozapine were included
      in the study. When all diagnostic groups were combined, there were no significant
      differences in clinical outcome between patients with abnormal EEGs and patients
      with normal EEGs. However, female patients with abnormal EEGs had a significantly
      greater improvement in Global Assessment of Functioning (GAF) scores compared to
      female patients with normal EEGs. In addition, patients with major depressive
      episodes (bipolar, schizoaffective, unipolar) and abnormal EEGs had a
      significantly greater improvement in GAF scores compared to the same subgroup of
      patients with normal EEGs. The results suggest that EEG abnormalities before
      clozapine treatment many predict a favorable clinical response in specific groups
      of patients.

PMID- 8743642
TI  - Fluoxetine treatment of anger attacks: a replication study.
AB  - "Anger attacks" are outbursts of anger which are accompanied by intense autonomic
      arousal and are clearly inappropriate to the situation in which they occur. The
      Anger Attacks Questionnaire, designed to assess these attacks, was administered
      to 164 consecutive patients (78 men and 86 women; mean age, 40.5 +/- 11.0 years)
      diagnosed as having major depression with the Structured Clinical Interview for
      DSM-III-R. These patients were treated openly with fluoxetine, 20 mg/day for 8
      weeks, and the prevalence of anger attacks was assessed before and after
      treatment. At baseline, 64 (39%) (26 men and 38 women) of these patients reported
      having anger attacks according to our criteria. Forty-one (64%) of the 64
      depressed patients with anger attacks at baseline did not report anger attacks
      following fluoxetine treatment, while 7 (7%) of the 100 patients who did not have
      anger attacks at baseline reported these attacks following treatment, with this
      difference being statistically significant (chi 2 = 22.7, p < .0005).

PMID- 8743643
TI  - Admission criteria for inpatient substance abuse/dependence rehabilitation:
      implications for managed care.
AB  - In view of recent trends toward the replacement of traditional inpatient
      rehabilitation programs with nonresidential services, we examined the extent to
      which patients currently admitted to inpatient rehabilitation for alcohol or drug
      abuse/dependence met published criteria suggesting a preferential need for
      inpatient or residential care. Over 90% of almost 300 veterans with a primary DSM
      III R diagnosis of alcohol or substance abuse/dependence, admitted to six New
      York Metropolitan Area Veterans Administration Medical Centers for inpatient
      rehabilitation, met at least one criterion dimension considered indicative of a
      need for such services, with over two-thirds meeting two or more dimensions.
      These findings suggest a continuing need for initial primary inpatient or
      residential rehabilitation for such patients.

PMID- 8743644
TI  - A target-dose finding study of clozapine in patients with schizophrenia.
AB  - Evidence from recent studies suggests that clozapine plasma concentrations
      greater than 350 ng/ml are correlated with therapeutic response. However, little
      is known about the clozapine dosages required to achieve these plasma
      concentrations. The purpose of this study was to determine if a target dose of 6
      mg/kg/day of clozapine would produce a steady state plasma concentration of > 350
      ng/ml. Twelve patients with schizophrenia by DSM-III-R criteria who were
      refractory to treatment with standard antipsychotics were treated with clozapine
      utilizing a 10- to 14-day titration to a target dose of 6 mg/kg/day. The mean (+/
      SD) clozapine plasma concentration achieved after 5 days at the target dose was
      584 +/- 417 ng/ml. Thus, although the target dose successfully produced
      therapeutic plasma concentrations for most patients, a wide variation was also
      apparent.

PMID- 8743645
TI  - L-Deprenyl augmentation of fluoxetine in a patient with Huntington's disease.
AB  - Fluoxetine and L-deprenyl were prescribed concurrently in a 19-year-old female
      with Huntington's disease. The patient showed significant affective, behavioral,
      and motoric improvements and there was no adverse effect resulting from this
      combination. Concomitant use of L-deprenyl in low doses and fluoxetine may be
      safe and beneficial in certain clinical situations, although further study is
      needed.

PMID- 8743646
TI  - Improvement of debilitating tardive dyskinesia with risperidone.
AB  - This case vignette illustrates dramatic improvement of tardive dyskinesia (TD) in
      an elderly female with a long history of neuroleptic exposure, following
      treatment with low-dose risperidone. The TD continued to be in remission at 1
      year follow-up. This observation calls for well-designed randomized studies to
      evaluate the efficacy of risperidone in treating TD.

PMID- 8743647
TI  - Obstruction of ECT seizure by submaximal hyperventilation: a case report.
AB  - Extreme obstruction of ECT seizure induction occurred in an elderly female with a
      low cardiac ejection fraction after a 20 to 25 s interval between the last
      ventilation and the electrical stimulus. Stimuli of 378 and 504 mC induced no
      motoric or EEG activity after an initial stimulus of 227 mC produced just 1 s of
      motoric seizure activity. After prolonged hyperventilation and immediate
      stimulation a seizure resulted with 33 s of motoric activity. This case suggests
      that patients with a low cardiac output might be particularly sensitive to the
      quality of ventilation.

PMID- 8743648
TI  - The dexamethasone suppression test for diagnosing depression in stroke patients.
AB  - Depression following a cerebrovascular accident is common, disabling, and
      treatable. However, the consequences of a stroke often render the clinical
      evaluation for depression misleading or difficult to interpret. These factors
      make a laboratory test for depression especially desirable in this population. We
      reviewed and evaluated the literature on the dexamethasone suppression test (DST)
      as a diagnostic tool for depression in stroke patients. Nine studies were
      identified. Our findings included (1) substantial variation in both methods and
      results, (2) a median specificity of 87%, and (3) a median sensitivity of 47%. We
      show that if these estimates of sensitivity and specificity are supported by
      future studies with improved methodology, then the DST may be clinically useful
      for the minority of stroke patients in whom a careful evaluation for depression
      remains inconclusive.

PMID- 8743649
TI  - "Smart drugs"?

PMID- 8743650
TI  - Endoscopic-assisted midface lift utilizing retrograde dissection.
AB  - Endoscopic facial surgery is gaining wide acceptance, as results are providing
      comparable if not superior to the standard, superficial musculoaponeurotic system
      rhytidectomy, with minimal scarring. Frontal branch facial nerve injury remains a
      troublesome complication. The purpose of our study was to determine if a
      subciliary retrograde dissection would decrease facial nerve injury and allow for
      more accurate midfacial suspension. Fresh cadaver dissections were performed
      using endoscopic equipment. Anterograde temporal incisions in the scalp and
      retrograde subciliary incisions were studied. The anterograde temporal dissection
      was developed deep to the superficial layer of the deep temporal fascia.
      Retrograde subciliary dissection was subperiosteal. Forty-nine endoscopic
      assisted midface lifts were performed. Midfacial suspension was accomplished with
      nonabsorbable sutures placed in the suborbicularis oculi fascia, anchored to the
      deep temporal fascia. Two of three endoscopic-assisted procedures done in the
      anterograde fashion, without a subciliary incision, experienced transient frontal
      branch injury, which resolved within 6 weeks. The remaining forty-six patients,
      operated with a combined subciliary and temporal approach, experienced no frontal
      branch injuries. We have found that the retrograde dissection through a
      subciliary incision substantially reduced the incidence of facial nerve injury,
      provided direct visualization of the suborbicularis oculi fascial layer (allowing
      more accurate midfacial suspension), and reduced total operative time.

PMID- 8743651
TI  - Transverse glabellar flap for obliteration/isolation of the nasofrontal duct from
      the anterior cranial base.
AB  - Management of fractures involving the nasofrontal duct region of the frontal
      sinus has focused on preserving function when possible or obliterating the sinus
      and duct when fracture patterns potentiate ductal obstruction and possible
      transcranial seeding of bacteria. When frontal sinus preservation is in doubt,
      controversy surrounds the use of cranialization versus obliteration, and the
      method of obliteration. Perioperative and late postoperative infections are
      uncommon, but their occurrence jeopardizes an often complex reconstruction and
      can be life threatening. This paper describes the design and indications for a
      pedicled transverse glabellar muscle flap for obliteration of the nasofrontal
      duct, thereby isolating the anterior cranial base from the aerodigestive system.
      This vascularized muscle flap utilizes the corrugator supercilii and procerus
      muscles, which are introduced into the sinus via a small, surgically created
      window in the superomedial orbital wall without disturbing the central facial
      aesthetic contours. Six patients with comminuted fractures at the nasofrontal
      duct level associated with displaced posterior frontal sinus fractures have been
      treated with the transverse glabellar flap. Follow-up ranges from 8 to 30 months.
      There have been no early or late postoperative complications. The transverse
      glabellar flap is a reliable and versatile method of partitioning the upper
      aerodigestive tract from the anterior cranial base with vascularized tissue, thus
      minimizing the risk of infectious complications. The resulting donor site
      deformity is more acceptable than that seen with the traditional pedicled galeal
      frontalis flap.

PMID- 8743652
TI  - Endoscopic-assisted carpal tunnel release: a coupling of endoscopic and open
      techniques.
AB  - Endoscopic-assisted carpal tunnel release (CTR) is a blending of the techniques
      of the open and endoscopic methods of carpal tunnel release. Endoscopic-assisted
      CTR increases visualization and safety over commonly performed endoscopic
      techniques while retaining the advantage of a smaller, more distally located scar
      and less dissection.

PMID- 8743653
TI  - Midpalmar approach to the carpal tunnel: an alternative to endoscopic release.
AB  - The midpalmar approach involves making a 2.5-cm incision in the palm, sparing the
      skin directly overlying the carpal tunnel. Through this incision, a small fiber
      optically illuminated retractor is introduced, which allows direct inspection of
      the transverse carpal ligament and any anatomic variations of the median nerve.
      The transverse carpal ligament can then be safely and completely divided under
      direct visualization. This approach also allows inspection of the carpal tunnel
      for any space-occupying masses or neurolysis, if deemed necessary. By avoiding a
      skin incision directly over the carpal tunnel, the postoperative course is very
      gentle and very similar to that of an endoscopic release. Unlike the endoscopic
      release, this approach is versatile, easy to learn, allows complete visualization
      of the anatomy, and does not require expensive instrumentation.

PMID- 8743654
TI  - Does ganglionectomy destabilize the wrist over the long-term?
AB  - Previous publications have described persistent postganglionectomy
      symptomatology. One report demonstrated scapholunate instability in a small
      number of patients. We specifically examined our ganglionectomy patients for
      wrist instability. Ninety-one consecutive cases of wrist ganglionectomy performed
      from 1987 through 1993 by the senior author (FMW) were studied. Most patients
      were contacted by telephone and questioned with a standardized interview format.
      Postoperative course, job changes and occupational restrictions, and patient
      satisfaction were queried. Range of motion, grip strength, scaphoid mobility, and
      radiographs were studied to characterize scapholunate static and dynamic
      relationships. Seventy-one percent (N = 61) of the operated patients were
      interviewed at an average postoperative interval of 44 months. Twenty-five
      percent (N = 21) had wrist symptoms. There was no late ganglion recurrence.
      Twenty of the 21 symptomatic patients (95%) had normal ranges of motion and no
      carpal instability. Grip strengths averaged 12% below normal in 45% of the
      dominant operated hands. Radiographs demonstrated no scapholunate dissociation or
      dynamic instability patterns. Wrist ganglionectomy does not destabilize the
      wrist, particularly the scapholunate joint. Thorough and meticulous extirpation
      of the ganglion is warranted. Additional minor problems, both as consequences of
      the operation and as unrelated concomitants, do occur and deserve attention. Hand
      surgeons assume cure of the problematic wrist because of the patient's failure to
      report tolerable problematic sequelae. A late revisit may reveal (1) treatable
      problems emanating from the dynamic forces contributing to original ganglion
      formation; (2) additional, unanticipated, treatable conditions resulting and not
      resulting from the ganglionectomy itself; and (3) ganglion recurrence.

PMID- 8743655
TI  - A classification of plagiocephaly utilizing a three-dimensional computer analysis
      of cranial base landmarks.
AB  - Plagiocephaly is a term commonly used to describe congenital forehead asymmetry.
      Previous classification systems based on the various etiologies of dysmorphic
      crania have been used in an effort to categorize the patients into groups and to
      assist in treatment planning. The system most commonly used today was described
      by Bruneteau and Mulliken in 1992. The authors separated frontal plagiocephaly
      into three types: synostotic, compensational, and deformational. The present
      study was undertaken in order to define a simple system for classifying
      plagiocephaly based on Bruneteau and Mulliken's system using the patients'
      preoperative craniofacial computed tomography scans. The involvement of the
      entire coronal ring in synostotic plagiocephaly led to the choice of 20 skull
      base landmarks as the basis of the analysis. Nine lateral landmarks (the superior
      orbital fissure, the optic foramen, the zygomatic arch, the greater palatine
      foramen, the foramen ovale, the mastoid tip, the hypoglossal canal, the external
      auditory canal, and the internal auditory canal) and two midline landmarks (the
      crista galli and the internal occipital protuberance) were used. The changes that
      occurred in these landmarks were analyzed in 30 patients. The results
      demonstrated that Bruneteau and Mulliken's classification system underestimated
      the number of different subtypes of plagiocephaly. As a result, three major types
      of frontal plagiocephaly and several different subtypes based on the different
      etiologies were described. Type I plagiocephaly includes plagiocephaly resulting
      from cranial suture synostosis. Type II includes those with a nonsynostotic
      etiology. Type III describes patients with craniofacial microsomia-associated
      plagiocephaly. Statistical analysis was unavailable because of the small number
      of patients in each subtype. With a larger number of patients, we hope to refine
      this system for use by the surgeon in preoperative diagnosis and surgical
      planning. The analysis is unique in its ability to quantitate changes from normal
      on the x-, y-, and z-coordinates, and therefore allows for identification of both
      horizontal (frontal bone deviation) and vertical (ear shear) growth disturbances.

PMID- 8743656
TI  - Staged reconstruction of abdominal wall defects after intra-abdominal
      catastrophes.
AB  - Advances in surgical intensive care have improved survival in patients with major
      traumatic or infectious intra-abdominal insults. Patients who recover are often
      left with massive abdominal wall defects. Sufficient autogenous tissue may not be
      available for reconstruction and synthetic mesh followed by skin grafting can
      lead to unaesthetic results or complications. We report on four patients with
      abdominal wall defects and their reconstruction after intra-abdominal injury.
      Treatment involved local wound care to stimulate granulation tissue, which is
      eventually skin grafted to close the wound. Patients are then allowed to make a
      full recovery. Soft-tissue expanding prostheses are placed during a second
      operation and inflated over subsequent weeks. Finally, the skin graft is excised,
      a polytetrafluoroethylene patch is placed into the fascial defect, and the
      expanded skin is used to achieve wound closure.

PMID- 8743658
TI  - Bell flap nipple reconstruction--a new wrinkle.
AB  - This single-stage nipple reconstruction technique is designed to produce a
      properly pigmented nipple-areolar complex that projects well above the breast
      mound without the need of skin grafts. The basic design of this technique
      consists of a bell-shaped random pattern flap within a circular subcutaneous
      island flap. The bell-shaped flap is incised, undermined, elevated, and folded
      into the shape of an inverted box, forming the new nipple. The remainder of the
      circular island flap is circumferentially incised, partially undermined, and
      sutured into a flat cone, forming the new areola. The nipple is inset in the
      center of this cone, completing the new nipple-areolar complex. This complex is
      then squeezed and pushed forward by the closure of a purse string suture placed
      on the raw edge of the outer skin circle. Predetermined pigments are tattooed
      immediately prior to the skin incisions and Montgomery's tubercles can be added
      after the pursestring closure by high-temperature cautery or biopsy punch. This
      technique has been attempted on six nipples in 5 patients for breast mounds
      reconstructed by musculocutaneous flaps or from breast reductions with
      satisfactory-to-good results in the past 2 1/2 years. However, at this time, it
      has not been, nor should it be attempted on breast mounds reconstructed solely by
      implants, due to unpredictable subcutaneous blood supply.

PMID- 8743657
TI  - Immediate skin expansion: an old concept by a novel and inexpensive technique.
AB  - Intraoperative skin expansion is not a new concept. We have developed a technique
      using readily available inexpensive material to achieve wound closure. In this
      prospective study, 15 patients (age range, 1-72 years) with melanoma, giant nevi,
      scars, meningocele, gastroschisis, alopecia, thrombosed renal dialysis fistula,
      calcified nodule and trauma, with defects on back, limbs, abdomen, scalp, hand,
      calcaneum, and sole of foot were treated. Only hypodermic needles and dental
      wire, with an overall cost of less than a dollar, are needed for the immediate
      skin expansion technique. In contrast, the numerous other commercial devices
      currently in use are costly and must be ordered in advance. Using our technique,
      the wound can be gradually approximated and subcutaneous sutures placed with the
      device in situ. An intradermal or simple running suture is then placed to
      approximate the skin edges under little or no tension and the device is removed.
      All patients had a good result with minimal morbidity. The wounds treated by this
      technique healed by primary intention except in 3 patients, who developed minor
      dehiscence of the wounds.

PMID- 8743659
TI  - Thrombocytosis after major lower extremity trauma: mechanism and possible role in
      free flap failure.
AB  - Microvascular thrombosis and free flap failure are complications of free tissue
      transfer for coverage of lower extremity soft-tissue and bony defects despite
      appropriate vessel selection and adherence to meticulous technique. Increased
      rates of flap failure have been associated with reconstruction performed between
      3 days and 6 weeks after injury, as well as in patients with thrombocytosis. We
      have found that serum platelet levels rise significantly after lower extremity
      injury. It is our theory that a circulating mediator or cytokine is released in
      response to injury, inducing the thrombocytosis. Twenty-one patients with Gustilo
      grade IIIb and IIIc injuries were studied prospectively. Serum was collected
      throughout the postinjury period. Platelet count, leukocyte count, hemoglobin
      concentration, and hematocrit were determined. Samples were also subjected to a
      platelet aggregation study as well as enzyme-linked immunosorbent assay for
      interleukin-3, interleukin-6, interleukin-11, and granulocyte macrophage-colony
      stimulating factor. Megakaryocyte growth and development factor enzyme-linked
      immunosorbent assay and a myleoproliferative leukemia virus-transfected cell line
      assay for thrombopoietin were performed. Bone marrow was studied with flow
      cytometric analysis. Mean initial platelet count was 196,000 per cubic
      millimeter. There was an initial 26% decline to 140,000 per cubic millimeter,
      followed by an increase to 361% of baseline on day 16. No significant variations
      in serum leukocyte count or hemoglobin concentration were seen. Spontaneous and
      induced platelet aggregation responses were normal. Interleukin-6 was detected at
      elevated levels. However, interleukin-3, interleukin-11, granulocyte macrophage
      colony-stimulating factor, and thrombopoietin were not measurable. Marked
      megakaryocytosis was seen on bone marrow analysis. Interleukin-6 may, therefore,
      play a role in the mechanism of thrombocytosis. We suggest that because patients
      with complex bony injuries of the leg experience platelet elevations that peak
      approximately 2 weeks after injury, microvascular free flap reconstructions
      should be considered high risk during this time period.

PMID- 8743660
TI  - Role of growth factors in scar contraction: an in vitro analysis.
AB  - Excessive scar contracture by wound fibroblasts can have devastating
      consequences, ranging from body disfigurement to joint immobility. The ability of
      fibroblasts isolated from lesions of hypertrophic scars, keloids, normal skin, or
      normal scars in contracting the provisional wound matrix (i.e., fibrin clot) was
      compared and analyzed. Hypertrophic scar fibroblasts showed a consistently higher
      basal level of fibrin matrix gel (FMG) contraction than other fibroblasts. This
      heightened basal level of contractility may be attributed partially to the
      autocrine effect of transforming growth factor-beta 1 (TGF-beta 1). Normal and
      keloid fibroblasts exhibited similar basal rates of FMG contraction, and both
      responded to platelet-derived growth factor (PDGF) and TGF-beta by increasing FMG
      contraction two- to threefold. However, 45% of the TGF-beta-induced increase in
      FMG contraction by keloid fibroblasts, but not normal fibroblasts, was mediated
      by the autocrine production of PDGF. Therefore, fibroblasts isolated from
      different scars exhibit varied degrees of FMG contraction. In addition, the
      mechanism underlying growth factor-mediated contraction differed vastly among
      fibroblasts of different scar origin. The significance of these differences in
      growth factor-mediated FMG contraction is discussed.

PMID- 8743661
TI  - Porcine gastroepiploic artery as an in vitro experimental model to study
      vasodilators in microsurgery.
AB  - Arterial vasospasm is a common problem in microsurgery. This pharmacological
      study compares seven vasodilators-lidocaine, papaverine, nicardipine, verapamil,
      diltiazem, sodium nitroprusside, and hydralazine-for their efficacy and potency
      in an experimental model of vasospasm. Porcine gastroepiploic arteries were cut
      into rings to measure isometric tension development in vitro. The arteries were
      preconstricted with endothelin-1, a stable thromboxane A2 analogue,
      norepinephrine, or potassium, and then exposed to increasing concentrations of
      each vasodilator. Every vasodilator except hydralazine and sodium nitroprusside
      was efficacious in producing near-maximal relaxation of arteries preconstricted
      with any vasospastic substance. The five efficacious vasodilators differed
      markedly in potency, as reflected in the concentrations producing half-maximal
      relaxation. The order of potency was nicardipine < or = verapamil or diltiazem <
      papaverine < lidocaine. This study suggests that nicardipine would be the most
      potent vasodilator for systemic or direct intra-arterial administration.
      Papaverine and lidocaine, in concentrations employed clinically, were both
      efficacious as topical vasodilators.

PMID- 8743662
TI  - Cushing's syndrome in postburn children following intralesional triamcinolone
      injection.
AB  - Intralesional triamcinolone acetonide has been used extensively for the treatment
      of hypertrophic and keloid scars. Complications are few, usually being local skin
      color changes, prominent vascular markings, or subcutaneous atrophy. Cushing's
      syndrome following intralesional administration of triamcinolone acetate has only
      been described twice, both in adult patients. This paper reports on two pediatric
      cases of Cushing's syndrome following treatment of hypertrophic burn scars with
      intralesional triamcinolone acetonide. The first child, 10 years of age, was
      treated for hypertrophic burn scars of the back. The second child, age 21 months,
      was treated for hypertrophic burn scars of the face. In both, intralesional
      triamcinolone acetate therapy was initiated 3 months postburn injury and in
      neither child was the maximum recommended dose exceeded. In both children,
      Cushing's manifestations developed 1 to 2 weeks postinjection and resolved in 6
      to 8 weeks with no treatment or permanent sequelae. Consultation with
      endocrinologists revealed no concurrent disease process. It appears that these
      two pediatric patients may have had a form of hypersensitivity to triamcinolone
      acetonide, as Cushing's syndrome was not the result of an overdose. In
      conclusion, intralesional triamcinolone acetonide should be used with an
      increased degree of caution in the pediatric population.

PMID- 8743663
TI  - Increase of immunologically relevant parameters in correlation with Baker
      classification in breast implant recipients.
AB  - A variety of studies have suggested a possible immune reaction to silicone
      implants, although an increased frequency of rheumatic disorders among implant
      recipients could not be established. Several immunologically relevant humoral
      parameters were investigated in 239 breast implant recipients. The following
      parameters were determined: immunoglobulin G and M, complement C3 and C4,
      rheumatoid factor, C-reactive protein, antinuclear antibodies, antimitochondrial
      antibodies, and antithyroglobulin and antimicrosomal antibodies of the thyroid
      gland. Levels of complement C3 were elevated in 42.5% of the patients. No
      difference could be observed between silicone gel-filled and saline-filled
      implant recipients. Complement C4 was increased in 21.3% of the patients and a
      parallel relationship was observed between elevated C4 and C3 levels (p <
      0.0015). In 28% of the patients, the antithyroglobulin titer was elevated > 200
      U/ml. No difference was found between silicone gel-filled and saline-filled
      implant recipients. Elevation of antimicrosomal antibodies existed in 14.3% of
      the patients and was correlated significantly with antithyroglobulin antibodies
      (p < 0.0347). In accordance with the classification developed by Baker, we
      observed a significant correlation between capsule fibrosis types Baker I and II,
      and elevated C3 values (p < 0.0004) in silicone gel-filled but not in saline
      filled implant recipients. Additionally, a correlation was found between
      increased antithyroglobulin titers (< 200 U/ml) and capsule fibrosis types Baker
      I and II (p < 0.0001) in this group. In the study presented here, an increase of
      several humoral parameters could be demonstrated in breast implant recipients,
      although we failed to correlate these findings with any clinical symptoms.

PMID- 8743664
TI  - The ultrapulse carbon dioxide laser with computer pattern generator automatic
      scanner for facial cosmetic surgery and resurfacing.
AB  - The ultrapulse carbon dioxide laser has been used in 110 patients for resurfacing
      and 50 patients for facelift, eyelid, and forehead surgery. Skin resurfacing is
      able to remove layers of skin of 100 microns without bleeding. Use of the
      computer pattern generator automatic scanning device allows a very rapid, uniform
      treatment in a variety of geometric patterns, sizes, and densities. Hemostatic
      incision is possible for cosmetic surgery. Sequence of the laserbrasion procedure
      as well as patient preparation, selection for surgery, and postoperative care are
      detailed. Laser lower blepharoplasty through the transconjunctival approach is
      commonly done concurrently with skin resurfacing to smooth out fine rhytides and
      extra skin.

PMID- 8743665
TI  - The French-line abdominoplasty.
AB  - This study presents 50 consecutive cases of abdominoplasty utilizing the authors'
      French-line method. This technique incorporates the basic principles of more
      traditional abdominoplasty procedures with significant modifications that allow
      for more aggressive plication of the fascia for accentuation of the waistline and
      relatively short oblique lateral incisions that are easily concealed within the
      French-cut one-piece bathing suit or reasonably modest bikini. The technique
      lends itself to adjunctive intra-abdominal procedures such as cholecystectomy or
      hysterectomy and is a safe method of abdominal reconstruction following
      transverse rectus abdominis musculocutaneous flap breast reconstruction.
      Complications are no more frequent than with "traditional" techniques. The only
      absolute contraindication is the presence of chronic obstructive pulmonary
      disease; relative contraindications are the same as for other abdominoplasty
      procedures.

PMID- 8743666
TI  - Superficial versus deep: options in venous drainage of the radial forearm free
      flap.
AB  - We performed a fresh cadaver dissection study of the superficial venous system
      (cephalic vein and its branches) and the deep venous system (venae comitantes) of
      the radial forearm to assess the suitability of each system for venous
      anastomosis during free tissue transfer. We used methyl methacrylate to evaluate
      vessel diameters and anatomic variability of both venous systems. Colored
      radiopaque injectate allowed us to combine anatomic dissection with tissue
      radiographs. We discovered the cephalic vein to invariably be of larger caliber
      than the venae comitantes. Ensuring capture of the cephalic vein in the flap
      necessitated additional dorsoradial subcutaneous dissection beyond the boundaries
      of the skin flap in four of ten specimens. The vessel diameters of the venae
      comitantes in four cadavers were less than 2 mm. Proximal confluence of the two
      venae comitantes, and communication between the deep and superficial venous
      systems were encountered in only four cases. In these cases, had an anastomotic
      site been chosen proximal to such a communication to ensure greater vessel
      caliber, pedicle length probably would have made free tissue transfer unwieldy.
      We recommend mapping the course of the cephalic vein before flap elevation and
      maintaining a wide proximal subcutaneous pedicle to capture the best possible
      superficial drainage system. If the superficial venous system has been damaged
      (as by previous intravenous catheterization), one may not necessarily be able to
      rely on the vessel caliber of the deep venae comitantes for microvenous
      anastomosis.

PMID- 8743667
TI  - Microvascular free posterior interosseous flap and a comparison with the pedicled
      posterior interosseous flap.
AB  - The posterior interosseous flap has been used as a pedicled flap for coverage of
      hand wounds. However, the pedicled flap is associated with partial or even
      complete loss when there is venous congestion. This happens because it depends on
      retrograde venous drainage. Another pitfall of the pedicled posterior
      interosseous flap is the undetected damage to the communicating vessels between
      the anterior and posterior interosseous arteries before surgery. This would
      result in failure if the flap is used as a distally based flap. Thirty-four
      patients had been reconstructed with the microvascular free posterior
      interosseous flap. The free flap has a large draining vein. Flap survival rate
      was 97%. There was no venous congestion and no partial loss of the flap. It is
      thin, sensate, and reliable. The free posterior interosseous flap is indicated
      for coverage of the following wounds: (1) first web space and thumb, (2) radial
      side of the index and ulnar side of the small finger if a cross-finger flap
      cannot be used, and (3) defects at the dorsum of multiple fingers. It can also be
      used as a free fascial flap. The free posterior interosseous flap provides a
      reliable option for coverage of hand wounds. Previously, another 14 patients with
      hand wounds had been reconstructed with a pedicled posterior interosseous flap.
      The results of pedicled and free posterior interosseous flaps are compared.

PMID- 8743668
TI  - Total midface reconstruction after radical tumor resection: a case report and
      overview of the problem.
AB  - We report an unusual repair of a massive midface defect resulting from resection
      of a recurrent squamous cell carcinoma of the nasal vestibule. The defect
      included both maxillas, the hard palate, the upper lip, and all nasal and
      perinasal tissues. After treatment, reconstruction was accomplished using
      prostheses and autologous tissue transferred from local and distant sites. The
      osseous component of the transferred tissue permitted placement of
      osseointegrated implants for fixation of maxillary and nasal prostheses. The
      rationale for this reconstruction and the problems associated with midface
      reconstruction after radical tumor resection are discussed.

PMID- 8743669
TI  - A matter of industry.

PMID- 8743670
TI  - Re: Risk of dissemination of cancer to flap donor sites during immediate
      reconstructive surgery.

PMID- 8743671
TI  - Re: Facial plaque-type blue nevus and its reconstruction.

PMID- 8743672
TI  - Re: Does high-frequency (40-60 MHz) ultrasound imaging play a role in the
      clinical management of cutaneous melanoma?

PMID- 8743673
TI  - Re: Reduction mammaplasty for gigantomastia using inferiorly based pedicle and
      free nipple transplantation.

PMID- 8743674
TI  - Information services of the European Bioinformatics Institute.
AB  - The scope of the EBI is focused on providing better services to the scientific
      community. Technological advancements in the hardware area provide EBI with means
      of producing data much faster than before, and with greater accuracy since there
      is now a better technical ability to produce more exhaustive searches through
      larger indices. Hand in hand with the technological developments, research and
      development work is continuing on better indexing systems and more efficient ways
      of establishing and maintaining the future databases. The existing links of
      communication between EBI and the user community are exploited to study the needs
      of the scientific community, to provide better services, and to enhance the
      quality of databases by interpreting user feedback and updates. A very important
      goal is to enhance the awareness of the scientific (and, maybe even more, the
      nonscientific) public of the importance of the modern field of bioinformatics and
      to introduce special meetings and courses, in which more specific subjects will
      be studied in depth. Another aspect of this goal is to help in constructing
      special bioinformatics programs in university faculties. In such programs, in
      contrast to the existing layout, students will pursue studies in a combined
      environment that provides basic training in biology and in computation.
      Currently, one of the main problems in the field is that scientists are either
      biologists, who are self-educated in the field of computers and programming, or
      computer scientists without sufficient knowledge of biology. It is hoped that a
      combined program will provide a high level of education in both fields of
      interest at the appropriate ratios. Building an efficient and friendly interface
      between the EBI and the user community is the basis for any future development.
      This aim is achieved by using the most modern server systems while continuously
      researching newer and better systems and interfaces. This task can never be
      complete without involvement of the user community by providing feedback to any
      of EBI's services. A better bioinformatics community is a necessity for any
      future development of the biological research aiming at a better society.

PMID- 8743675
TI  - TDB: new databases for biological discovery.

PMID- 8743676
TI  - PIR-International Protein Sequence Database.

PMID- 8743677
TI  - Superfamily classification in PIR-International Protein Sequence Database.

PMID- 8743678
TI  - Gene classification artificial neural system.

PMID- 8743679
TI  - Blocks database and its applications.
AB  - Protein blocks consist of multiply aligned sequence segments without gaps that
      represent the most highly conserved regions of protein families. A database of
      blocks has been constructed by successive application of the fully automated
      PROTOMAT system to lists of protein family members obtained from Prosite
      documentation. Currently, Blocks 8.0 based on protein families documented in
      Prosite 12 consists of 2884 blocks representing 770 families. Searches of the
      Blocks Database are carried out using protein or DNA sequence queries, and
      results are returned with measures of significance for both single and multiple
      block hits. The databse has also proved useful for derivation of amino acid
      substitution matrices (the Blosum series) and other sets of parameters. WWW and E
      mail servers provide access to the database and associated functions, including a
      block maker for sequences provided by the user.

PMID- 8743680
TI  - Indexing and using sequence databases.

PMID- 8743681
TI  - SRS: information retrieval system for molecular biology data banks.

PMID- 8743682
TI  - Applications of network BLAST server.
AB  - The sequence databases continue to grow at an extraordinary rate. Contributions
      come from both small laboratories and large-scale projects, such as the Merck EST
      project. This growth has placed new demands on computational sequence comparison
      tools such as BLAST. Even now it is no longer practical to evaluate some BLAST
      reports manually; it is necessary to filter the output by, for example, organism,
      source, or degree of annotation. The new network BLAST service makes such tools
      possible. It is also possible to present BLAST output in different formats, such
      as BLANCE. Perhaps most important of all, it becomes simple to call BLAST from
      another application, making it one step within an integrated system. This makes
      the automated preparation of sequence evaluations that include BLAST runs
      possible. In the near future we expect to see a number of applications that use
      the network BLAST interface to help molecular biologists search against a
      database that is growing not only in size but in biological richness.

PMID- 8743683
TI  - Entrez: molecular biology database and retrieval system.

PMID- 8743684
TI  - Applying motif and profile searches.

PMID- 8743685
TI  - Consensus approaches in detection of distant homologies.

PMID- 8743686
TI  - Identification of sequence pattern with profile analysis.

PMID- 8743687
TI  - Effective large-scale sequence similarity searches.

PMID- 8743688
TI  - Effective protein sequence comparison.
AB  - Although there are several different comparison programs available (e.g., BLASTP,
      FASTA, SSEARCH, and BLITZ) that can be used with different scoring systems (e.g.,
      PAM120, PAM250, BLOSUM50, BLOSUM62) and different databases (e.g., PIR, SWISS
      PROT, GenPept), the following search protocol should identify homologous
      sequences whenever they can be found. 1. Always compare protein sequences if the
      genes encode proteins. Protein sequence comparison will typically double the
      evolutionary lookback time over DNA sequence comparison. 2. Search several
      sequence databases using a rapid sequence comparison program (e.g., BLASTP or
      FASTA, ktup = 2). Well-curated databases like PIR or SWISS-PROT tend to have
      fewer redundant sequences, which improves the statistical significance of a
      match, but they are less comprehensive and up-to-date than GenPept. 3. If there
      is good agreement between the distribution of scores and the theoretical
      distribution, and the alignments do not include "simple sequence" domains, accept
      sequences with FASTA E() values or BLASTP P() values below 0.02 as homologous. 4.
      If no library sequences are found with E values below 0.02, perform additional
      searches with FASTA, ktup = 1, or SSEARCH. If library sequences with E values
      less than 0.02 are found, the sequences are probably homologous, unless a low
      complexity domain is aligned. However, sequences with similarity scores from 0.02
      to 10.0 may be homologous as well. To characterize these more distantly related
      sequences, select "marginal" library sequences and use them to search the
      databases. Additional family members should have E values less than 0.05. 5.
      Homologous sequences share a common ancestor, and thus a common protein fold.
      Depending on the evolutionary distance and divergence path, two or more
      homologous sequences may have very few absolutely conserved residues. However, if
      homology has been inferred between A and B, between B and C, and between C and D,
      A and D must be homologous, even if they share no significant similarity. 6.
      Sequences with marginal E values should also be tested using the PRSS program.
      Compare the query and library sequences using at least 200 (and preferably 1000)
      shuffles. Shuffles using a window (-w) of 10-20 are more stringent than a uniform
      shuffle. Use the E value after 1000 shuffles to confirm an inference of homology.
      7. Homologous sequences are usually similar over an entire sequence or domain,
      typically sharing 20-25% or greater identity for more than 200 residues. Matches
      that are more than 50% identical in a 20- to 40-amino acid region occur
      frequently by chance and do not indicate homology. By following these steps, one
      will very rarely assert that two sequences are homologous when in fact they are
      not. However, these criteria are stringent; distantly related homologous
      sequences may fail to be detected because their similarity is not statistically
      significant. These tests are biased toward missing some distantly related
      sequences to avoid the possibility of misidentifying unrelated ones. In most
      database searches, the ratio of related to unrelated sequences is more than
      4000:1 (e.g., 10 related and 40,000 unrelated sequences). Thus, one is more
      likely to mistakenly identify two sequences as related than to overlook a genuine
      relationship, and our conservative evaluation criteria reflect that bias.

PMID- 8743689
TI  - Discovering and understanding genes in human DNA sequence using GRAIL.

PMID- 8743690
TI  - Linguistic analysis of nucleotide sequences: algorithms for pattern recognition
      and analysis of codon strategy.

PMID- 8743691
TI  - Protein sequence comparison at genome scale.
AB  - An adequate set of computer procedures tailored to address the task of genome
      scale analysis of protein sequences will greatly increase the beneficial impact
      of the genome sequencing projects on the progress of biological research. This is
      especially pertinent given the fact that, for model organisms, one-half or more
      of the putative gene products have not been functionally characterized. Here we
      described several programs that may comprise the core of such a set and their
      application to the analysis of about 3000 proteins comprising 75% of the E. coli
      gene products. We find that the protein sequences encoded in this model genome
      are a rich source of information, with biologically relevant similarities
      detected for more than 80% of them. In the majority of cases, these similarities
      become evident directly from the results of BLAST searches. However, methods for
      motif analysis provide for a significant increase in search sensitivity and are
      particularly important for the detection of ancient conserved regions. As a
      result of sequence similarity analysis, generalized functional predictions can be
      made for the majority of uncharacterized ORF products, allowing efficient
      focusing of experimental effort. Clustering of the E. coli proteins on the basis
      of sequence similarity shows that almost one-half of the bacterial proteins have
      at least one paralog and that the likelihood that a protein belongs to a small or
      a large cluster depends on the function of this particular protein.

PMID- 8743692
TI  - Iterative template refinement: protein-fold prediction using iterative search and
      hybrid sequence/structure templates.

PMID- 8743693
TI  - Multiple protein sequence alignment: algorithms and gap insertion.

PMID- 8743694
TI  - Progressive alignment of amino acid sequences and construction of phylogenetic
      trees from them.

PMID- 8743695
TI  - Using CLUSTAL for multiple sequence alignments.
AB  - We have tested CLUSTAL W in a wide variety of situations, and it is capable of
      handling some very difficult protein alignment problems. If the data set consists
      of enough closely related sequences so that the first alignments are accurate,
      then CLUSTAL W will usually find an alignment that is very close to ideal.
      Problems can still occur if the data set includes sequences of greatly different
      lengths or if some sequences include long regions that are impossible to align
      with the rest of the data set. Trying to balance the need for long insertions and
      deletions in some alignments with the need to avoid them in others is still a
      problem. The default values for our parameters were tested empirically using test
      cases of sets of globular proteins where some information as to the correct
      alignment was available. The parameter values may not be very appropriate with
      nonglobular proteins. We have argued that using one weight matrix and two gap
      penalties is too simplistic to be of general use in the most difficult cases. We
      have replaced these parameters with a large number of new parameters designed
      primarily to help encourage gaps in loop regions. Although these new parameters
      are largely heuristic in nature, they perform surprisingly well and are simple to
      implement. The underlying speed of the progressive alignment approach is not
      adversely affected. The disadvantage is that the parameter space is now huge; the
      number of possible combinations of parameters is more than can easily be examined
      by hand. We justify this by asking the user to treat CLUSTAL W as a data
      exploration tool rather than as a definitive analysis method. It is not sensible
      to automatically derive multiple alignments and to trust particular algorithms as
      being capable of always getting the correct answer. One must examine the
      alignments closely, especially in conjunction with the underlying phylogenetic
      tree (or estimate of it) and try varying some of the parameters. Outliers
      (sequences that have no close relatives) should be aligned carefully, as should
      fragments of sequences. The program will automatically delay the alignment of any
      sequences that are less than 40% identical to any others until all other
      sequences are aligned, but this can be set from a menu by the user. It may be
      useful to build up an alignment of closely related sequences first and to then
      add in the more distant relatives one at a time or in batches, using the profile
      alignments and weighting scheme described earlier and perhaps using a variety of
      parameter settings. We give one example using SH2 domains. SH2 domains are
      widespread in eukaryotic signalling proteins where they function in the
      recognition of phosphotyrosine-containing peptides. In the chapter by Bork and
      Gibson ([11], this volume), Blast and pattern/profile searches were used to
      extract the set of known SH2 domains and to search for new members. (Profiles
      used in database searches are conceptually very similar to the profiles used in
      CLUSTAL W: see the chapters [11] and [13] for profile search methods.) The
      profile searches detected SH2 domains in the JAK family of protein tyrosine
      kinases, which were thought not to contain SH2 domains. Although the JAK family
      SH2 domains are rather divergent, they have the necessary core structural
      residues as well as the critical positively charged residue that binds
      phosphotyrosine, leaving no doubt that they are bona fide SH2 domains. The five
      new JAK family SH2 domains were added sequentially to the existing alignment of
      65 SH2 domains using the CLUSTAL W profile alignment option. Figure 6 shows part
      of the resulting alignment. Despite their divergent sequences, the new SH2
      domains have been aligned nearly perfectly with the old set. No insertions were
      placed in the original SH2 domains. In this example, the profile alignment
      procedure has produced better results than a one-step full alignment of all 70
      SH2 domains, and in considerably less time. (ABSTRACT TRUNCATED)

PMID- 8743696
TI  - Combined DNA and protein alignment.

PMID- 8743697
TI  - Inferring phylogenies from protein sequences by parsimony, distance, and
      likelihood methods.

PMID- 8743698
TI  - Reconstruction of gene trees from sequence data.

PMID- 8743699
TI  - Estimating evolutionary distances between DNA sequences.

PMID- 8743700
TI  - Local alignment statistics.

PMID- 8743701
TI  - Parametric and inverse-parametric sequence alignment with XPARAL.

PMID- 8743702
TI  - Identification of functional residues and secondary structure from protein
      multiple sequence alignment.

PMID- 8743703
TI  - Prediction and analysis of coiled-coil structures.

PMID- 8743704
TI  - PHD: predicting one-dimensional protein structure by profile-based neural
      networks.

PMID- 8743705
TI  - GOR method for predicting protein secondary structure from amino acid sequence.

PMID- 8743706
TI  - Analysis of compositionally biased regions in sequence databases.

PMID- 8743707
TI  - Discrimination of common protein folds: application of protein structure to
      sequence/structure comparisons.

PMID- 8743708
TI  - Three-dimensional profiles for measuring compatibility of amino acid sequence
      with three-dimensional structure.

PMID- 8743709
TI  - SSAP: sequential structure alignment program for protein structure comparison.

PMID- 8743710
TI  - Understanding protein structure: using scop for fold interpretation.

PMID- 8743711
TI  - Detecting structural similarities: a user's guide.

PMID- 8743712
TI  - Alignment of three-dimensional protein structures: network server for database
      searching.

PMID- 8743713
TI  - Converting sequence block alignments into structural insights.

PMID- 8743714
TI  - Erythrocyte rheology in microcirculation.

PMID- 8743715
TI  - Pathological aspects of active oxygens/free radicals.

PMID- 8743716
TI  - Quantitative characterization of P-glycoprotein-mediated transport in mdr1-gene
      transfected lymphoma cells.
AB  - We have established a quantitative flow cytometry system to elucidate the causal
      role of P-glycoprotein in the phenomenon of multidrug resistance. We have used
      this method to analyze the accumulation and release of adriamycin (ADM) in intact
      L5178Y and L5178Y/VMDR/C.06 (L5178Y/R) cells, by determining the effect of sodium
      orthovanadate (Na3VO4), verapamil, bovine serum albumin (BSA) and physiologically
      operative materials on the cells. Based on the experiments, we prepared a
      standard solution that contained NaCl, D-glucose, L-cysteine, HCO3- and BSA,
      which was sufficient to perform transport experiments. In particular, BSA caused
      a decrease in ADM accumulation and a facilitation of the rate of ADM release in
      both L5178Y and L5178Y/R cells, probably due to its relatively high affinity for
      ADM as compared to the cell membrane. In multidrug-resistant L5178Y/R cells,
      sodium orthovanadate, a strong ATP-binding inhibitor, caused a marked increase in
      the accumulation of ADM, whereas vanadate-treated drug-sensitive L5178Y cells
      showed little increase in ADM accumulation. In a release (0-trans exit)
      experiment, vanadate-treated L5178Y/R cells exhibited an apparent decrease in ADM
      release (increase in ADM retention), to a level which was almost the same as
      L5178Y cells. We thus confirmed that the P-glycoprotein-mediated efflux system is
      coupled with P-glycoprotein-associated ATP-hydrolysis. Further, verapamil, a
      potent inhibitor of P-glycoprotein-mediated transport, facilitated the ADM
      accumulation in L5178Y/R cells up to the level of L5178Y and vanadate-treated
      L5178Y/R cells. A more important finding is that, in the release experiment,
      verapamil-treated L5178Y/R cells exhibited a much greater ADM retention than drug
      sensitive L5178Y and vanadate-treated L5178Y/R cells. These findings, in
      particular the potent effect of verapamil on drug-resistant cells, may afford new
      insight into the pathophysiology of the phenomenon of multidrug resistance and
      the mechanism of action of the multidrug transporter.

PMID- 8743717
TI  - Comparison of activation of non-selective cation channels by protein kinase-A in
      guinea-pig and mouse pancreatic acinar cells.
AB  - The effects of cyclic AMP-dependent protein kinase (PKA) on non-selective cation
      (NSC) channels in the plasma membrane of guinea-pig and mouse pancreatic acinar
      cells were studied by patch-clamp single-channel techniques. In both species, ATP
      (1.4 mM) acting on the inside of the membrane (Ca2+ concentration, 10(-6)M)
      inhibited the opening of the NSC channel with a unit conductance of 25 pS. The
      addition of a catalytic unit of PKA (25 U/ml) in the presence of ATP to the
      inside of guinea-pig cells evoked an opening of a new channel, which is a Ca(2+)
      activated and voltage-sensitive NSC channel with a unit conductance of about 45
      pS (in symmetrical monovalent cation-rich solution). On the other hand, 25 pS
      Ca(2+)-activated NSC channel in mouse cells was re-opened by identical PKA
      application. The application of PKA-inhibitor did not activate NSC channels in
      either species. The addition of 10(-6)M ACh to the bath solution containing 10(
      6)M insulin, whose addition with ACh has been reported to increase cAMP, evoked a
      marked and sustained increase in the opening of the guinea-pig 45 pS or the mouse
      25 pS NSC channel in intact cells (cell-attached configurations). This was not
      seen in the absence of insulin. These results suggest that the cAMP-dependent
      mechanism in the pancreatic acinar cells can activate NSC channels in the
      presence of ATP on the inside of the cell.

PMID- 8743718
TI  - Increases in gastric acidity in response to electroacupuncture stimulation of the
      hindlimb of anesthetized rats.
AB  - Acupuncture treatment has been used as physiotherapy to treat gastrointestinal
      disorders in traditional Oriental medicine. In the present study, we selected
      anesthetized animals as the subjects of this experiment in order to eliminate
      emotional factors, and investigated the responses to acupuncture stimulation at
      only a single point by changing animal conditions. 1) There was marked
      enhancement of gastric acid secretion by electroacupuncture stimulation of the
      hindlimb based on pH values of the perfusate. However, the enduring response
      after the momentary initial decrease suggested the existence of humoral factors.
      2) The electroacupuncture-specific response was not observed in rats after
      sciatic nerve denervation. However, the pH values of the perfusate decreased in
      response to electroacupuncture stimulation of the hindlimb on the sciatic nerve
      intact side of the same rat. This suggests that the input pathway of acupuncture
      stimulation was a somatic nerve efferent pathway from the hindlimb. 3) No
      response to electroacupuncture stimulation was observed in the rats after
      vagotomy, but a clear enhancement response was seen after sympathectomy. These
      findings show that the major efferent path of the responses to acupuncture
      stimulation is the vagus nerve. The results of this experiment suggest that
      electroacupuncture stimulation of the hindlimb of anesthetized rats increases
      gastric acid secretion with somatic nerves as the afferent pathway and branches
      of the vagus nerve to the stomach as the efferent pathway.

PMID- 8743719
TI  - Charge movement in overstretched amphibian skeletal muscle cut fibers.
AB  - Membrane current experiments were done in the absence of any permeable ion
      (except calcium) and the presence of TTX (tetrodotoxin) and TEA+
      (tetraethylammonium) in the external solution and caesium in the internal
      solution at two different sarcomere lengths (3.8 and 4.56 microns) in skeletal
      muscle fibers of frog (pipiens). Single cut fibers were voltage-clamped in a
      double Vaseline gap apparatus, and intramembrane charge movement and slow calcium
      currents were measured. In order to obtain the charge movement, a conventional
      control was used (the response to a negative pulse) obtained in normally
      polarized fiber. A descriptive analysis of the results shows us that at 3.8
      microns the fibers respond with slow calcium current and charge movement with the
      characteristics of charge 1 (Q1), but at a sarcomere length of 4.56 microns, just
      a slow calcium current is obtained. The absence of intramembrane charge movement
      in overstretched fibers could suggest a modification in the transverse tubular
      system geometry obscuring the charge movement phenomenon (the linear membrane
      capacity in stretched fibers was 13.10 micro F/cm2 as average for 5 fibers and in
      overstretched ones was 13.61 micro F/cm2 as average for 11 fibers). The presence
      of slow calcium current in this condition (overstretched fiber) means an
      electrical connection of the tubule with superficial membrane and suggests that
      the charge movement does not correspond to gating of the "L" type calcium
      channel.

PMID- 8743720
TI  - Hematologic and body fluid changes during simulated high altitude exposure in
      naproxen-treated rats.
AB  - Arterial blood oxygen saturation, body fluid and hematological parameters were
      studied in control, naproxen (a prostaglandin synthesis inhibitor)-treated
      control, altitude-exposed, and naproxen-treated altitude-exposed rats after
      intermittent exposure of 8 h/d for 6 consecutive days to a simulated high
      altitude of 6,100 m (barometric pressure 349 +/- 3 mmHg). Arterial blood oxygen
      saturation was reduced in altitude-exposed rats, but increased significantly to
      near control level in naproxen-treated rats. On the other hand, 2,3
      diphosphoglycerate in erythrocytes increased in altitude-exposed rats, but
      naproxen prevented this increase. The red blood cell count, hemoglobin
      concentration and hematocrit ratio were reduced significantly in drug-treated
      altitude-exposed rats when compared to the altitude-exposed group (without drug).
      Red cell mass was increased in the altitude-exposed group in comparison with
      control. Both red cell mass and mean corpuscular volume of altitude-exposed rats
      were shifted towards the control value when they were treated with naproxen. Drug
      treated high altitude-exposure reduced the thiocyanate space, intracellular fluid
      volume and total body water content compared to drug-treated control rats. On the
      other hand, thiocyanate space and total body water content were increased
      significantly in drug-treated control rats in comparison with the control group.

PMID- 8743721
TI  - Na concentration of CSF and cardiovascular adjustment in thermally dehydrated
      rats.
AB  - To assess the effect of the Na concentration of cerebrospinal fluid (CSF) on
      arterial pressure regulation under dehydration, the Na concentration in CSF
      ([Na]csf) was measured continuously with an Na-sensitive electrode in the lateral
      ventricle (LV) together with mean arterial pressure (MAP), central venous
      pressure (CVP) and cardiac output (CO) during and after hypotonic infusion (INF,
      approximately 200 mOsm/kg H2O, 5 microliters/min for 10 min) into the LV of
      dehydrated and pentobarbital anesthetized rats. Total vascular conductance (TVC)
      was calculated from CO/(MAP-CVP). Sino-aortic denervation was performed to
      eliminate any influence of arterial baroreflexes on MAP changed by [Na]csf. After
      dehydration, MAP increased by 20 mmHg (p < 0.001) despite a 9% decrease in blood
      volume (p < 0.001) while [Na]csf increased by 13 mEq/kg H2O (p < 0.001). This
      increase in MAP was attributed to the decrease in TVC. After hypotonic INF began,
      MAP and [Na]csf decreased and the maximal decreases of -13 mmHg (p < 0.001) and 
      28 mEq/kg H2O (p < 0.001) were found at the end of INF, respectively. The changes
      in MAP (r = 0.97, p < 0.001), CO (r = 0.97, p < 0.001), and TVC (r = -0.90, p <
      0.001) were highly correlated with the change in [Na]csf during INF and the
      following 10-min recovery. These results suggest that the increase in [Na]csf is
      involved in the maintenance of arterial pressure by decreasing TVC and by
      attenuating the decrease in CO caused by dehydration-induced hypovolemia.

PMID- 8743722
TI  - Sympathoadrenal activity in the visceral (viscerovascular) reflexes to distension
      of the urinary bladder.
AB  - Distension of the urinary bladder can cause reflex pressor responses, which
      appear to be mediated by increased sympathetic activity. We correlated the
      involvement of the adrenal gland (medulla) itself and adrenosympathetic nerve
      activities with the viscerovascular reflexes and their role in controlling the
      reflex response following distension of the urinary bladder. The experiments were
      performed in 37 chloralose anesthetized cats. It was observed that reflex rise of
      blood pressure was not affected by intravenous administration of propranolol,
      indicating that the beta-adrenoceptors (inhibitory effect) were not involved in
      such reflex. Phentolamine, hexamethonium and guanethidine sulfate completely
      prevented the reflex action, and comparison of the magnitudes of responses and
      this inhibitory effect suggests the participation of alpha-adrenoceptors
      (excitatory effect) as a result of the vasoconstriction that develops during
      bladder distension. In the present study, we determined that adrenalectomy
      significantly (p < 0.0001) altered the magnitudes of reflex response during
      bladder distension. The 10.4% (systolic, p < 0.001) and 10.6% (diastolic, p <
      0.01) change in reflex response was mediated directly through adrenomedullary
      catecholamines, and the 14.8% (systolic, p < 0.001) and 23.8% (diastolic, p <
      0.0001) change in vasopressor response was mediated by adrenosympathetic
      ganglionic activity. The single unit activity from the central cut end of the
      adrenal sympathetic nerve was recorded for direct evidence. An increase in
      electrical activity (1-3 to 7-10 spikes/s; p < 0.001) of the adrenal sympathetic
      nerve with the rise of blood pressure during bladder distension was observed. We
      concluded that, like other sympathetic nerves, the adrenal sympathetic nerve
      contributed to the enhancement of blood pressure during bladder distension. This
      result also explains the partial inhibition of reflex hypertension during bladder
      distension after adrenalectomy. These studies also conclude that the adrenal
      gland and adrenosympathetic nerve act as facilitatory modulators in maintaining
      catecholamine secretion under conditions of stress (urinary bladder distension).

PMID- 8743723
TI  - Hormonal responses in strenuous jumping effort.
AB  - In order to test the possibility for rapid responses of blood hormone levels in
      short-term supramaximal exercises, serum concentrations of corticotropin (ACTH),
      cortisol (C), total testosterone (tT), free testosterone (fT), growth hormone
      (GH), thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3),
      prolactin (PRL), insulin-like growth factor (IGF-I), and sex hormone-binding
      globulin (SHBG) were determined by RIA procedures in blood samples obtained
      before and immediately after a 60-s period of consecutive vertical jumps (Bosco
      test). The study subjects were 16 Italian professional soccer players.
      Immediately after exercise, significant increases (p < 0.05) were found in the
      concentrations of ACTH (by 39%), C (by 14%), TSH (by 20%), fT3 (by 28%), fT4 (by
      30%), tT (by 12%), fT (by 13%), and SHBG (by 21%). Significant changes were not
      detected in the blood levels of GH, IGF-I and PRL. Most pronounced testosterone
      responses were typical for persons of high jumping performance (the increase of
      serum tT correlated with average power output, r = 0.61 and jumping height, r =
      0.66). The larger the drop in power output during 60-s jumping, the higher was
      the thyroid response: the difference in jumping height between the first and last
      15-s period correlated with increases in TSH (r = 0.52) and in fT4, (r = 0.55).
      In conclusion, the obtained results indicate that in intense exercise, causing
      the rapid development of fatigue, rapid increases in serum levels of hormones of
      the pituitary-adrenocortical, pituitary-gonadal and pituitary-thyroid systems
      occur.

PMID- 8743724
TI  - Picrotoxin potentiates contraction while inhibiting Ca current but increasing
      birefringence signal in frog skeletal muscle fibers.
AB  - In single frog skeletal muscle fibers, picrotoxin (5 mM) potentiated the voltage
      dependent component of contractions in response to 2-s depolarizing pulses while
      greatly inhibiting the simultaneously recorded tubular Ca current in a normal-Ca,
      Na- and CI-deficient solution, provided the contractions were generated at long
      time intervals (2 min). In normal Ringer's solution, picrotoxin reversibly
      increased the amplitude of the early large birefringence signal and the amplitude
      and duration of the simultaneously recorded twitch tension, suggesting that the
      drug may increase, directly or indirectly, the release of Ca from the SR.

PMID- 8743725
TI  - Ex-vivo and in-vivo platelet function in patients with severe
      hypercholesterolemia undergoing LDL-apheresis.
AB  - Patients with severe familial hypercholesterolemia (HC) show abnormal platelet
      function and shortened platelet survival. Atherosclerosis is associated with
      platelet hyperactivity. Low-density lipoporotein (LDL)-apheresis eliminates the
      most atherogenic lipid fraction and inhibits the progression of atherosclerosis
      inducing even regression. In order to assess the influence of LDL-apheresis on
      platelet function ex-vivo and in-vivo, 6 patients with severe heterozygous HC,
      all of them being pharmacologically treated with HMG-CoA reductase inhibitors and
      anion exchange resins were investigated. Ex-vivo platelet function was assessed
      by the aggregation response to ADP before starting apheresis treatment, as well
      as after 2 and 24 weeks, respectively. In-vivo platelet function was determined
      by measuring platelet survival after radiolabeling with 111In-oxine before
      starting LDL-apheresis and after 24 weeks of twice monthly treatment. LDL
      apheresis therapy induced a significant (p < 0.01) drop in cholesterol by 64%,
      LDL-cholesterol by 77% and in triglycerides by 46% over a period of 24 weeks. ADP
      induced platelet aggregation revealed a decreased aggregability of platelets with
      a decline in the maximal amplitude and the slope of the response curve. Changes
      in platelet sensitivity to prostaglandins (PG) were significantly for PGI2, but
      did not reach statistical significance for PGE1. The results revealed a
      significant (p < 0.001) increase in platelet survival of 111In-oxine-radiolabeled
      autologous platelets from a mean of 106.50 hours before to 137.50 hours (p <
      0.01) after treatment, being accompanied by an increase in labeling efficiency (p
      < 0.001) and recovery (p < 0.001). These data provide evidence for improved
      hemostatic regulation in vivo as a result of maintainance of lipid-lowering
      achieved with LDL-apheresis.

PMID- 8743726
TI  - Effect of active oxygen species scavengers on fibrinolytic activity of some
      proteinases.
AB  - Scavengers of different active oxygen species affect fibrin plate lysis,
      catalysed by various proteinases, only at relatively high concentrations (> 10(
      2) M). Singlet oxygen scavengers change proteinase activity insignificantly
      except for strong inhibition of pepsin and papain by sodium azide, but pepsin-by
      histidine, and fibrinolytic urokinase activity-by all used O2 delta 1 scavengers.
      Of all used scavengers of OH-radical only ethanol caused significant changes in
      the proteinases under study, except for alpha-chymotrypsin. The most strong
      inhibitory effect on proteinase activity was demonstrated by scavengers of
      superoxide radical. Thus, nitrotetrazolium blue strongly inhibited the activity
      of plasmin, urokinase (fibrinolytic activity), papain and pepsin. Catalase
      changed proteinase activity insignificantly, though it leads to total inhibition
      of pepsin activity at final 4.5 x 10(-4) M concentration. These facts and our
      previous findings on generating of active oxygen species by proteinases give us
      grounds to suppose that minor active oxygen species, endogenous for the
      "proteinase-substrate" system, can participate in the catalytic function of some
      proteinases.

PMID- 8743727
TI  - Soluble thrombomodulin antigen in plasma is increased in patients with acute
      myocardial infarction treated with thrombolytic therapy.
AB  - Thrombomodulin (TM) is an integral endothelial cell membrane protein that
      functions as a cofactor for thrombin mediated activation of protein C. The
      anticoagulant functions of the protein C system are important in contributing to
      a hemostatic balance and prevention of thromboembolic disease. It has been
      suggested that impaired TM cofactor function could also constitute a
      prothrombotic abnormality leading to thromboembolic diseases. TM exists not only
      on the surface of endothelial cells but also as soluble fragment(s) circulating
      in plasma. The concept of a thrombotic occlusion as the critical event in acute
      myocardial infarction (AMI) forms the rationale for thrombolytic therapy. After
      successful reperfusion, patients remain at substantial risk for recurrent
      infarctions due to rethrombosis. The balance between procoagulant and
      anticoagulant mechanisms in the postthrombolytic phase have not been studied in
      detail. We have studied whether the plasma levels of soluble TM are influenced by
      thrombolytic therapy with streptokinase in patients suffering from AMI. Soluble
      TM concentrations increased significantly by 24 to 48 h after thrombolytic
      treatment, simultaneously with an increase in C-reactive protein (CRP, a marker
      of the inflammatory component of the cell damage) and in thio-barbituric acid
      reactive substances (TBARS, an indirect marker of lipid peroxidation).

PMID- 8743728
TI  - Plasma stimulation of prostacyclin production by rat smooth muscle cells requires
      previous induction of phospholipase activity.
AB  - Human normal platelet poor plasma (PPPn) stimulates prostacyclin (PGI2)
      production in a dose-dependent manner and after 15 to 60 min of incubation time
      when confluent rat smooth muscle cells (RSMC) were preincubated for 24 hours with
      fresh culture medium. This PGI2 production was independent of new protein
      synthesis, and was not observed in the cells maintained only in exhausted medium.
      The serum of fresh culture medium also induced a significant and transient
      increase of prostaglandin endoperoxide synthase (PGHS) activity as a function of
      preincubation time, which was dependent of protein synthesis. However, neither
      PGHS activity nor arachidonic acid availability limited the PPPn induced PGI2
      synthesis in RSMC. Moreover, the previous addition of phorbol 13-myristate
      acetate also allowed the PPPn to induce PGI2 synthesis, that was significantly
      inhibited by a specific phospholipase A2 inhibitor. Furthermore, we found that
      PPPn induced a significant increase of intracellular calcium, and also stimulated
      PGI2 production at short incubation times due to its effect on phospholipases,
      and not by a direct supply of substrate. We conclude that a previous activation
      of phospholipase A2 was necessary to observe a significant and sustained PGI2
      synthesis induced by PPPn in RSMC, and that the increase of intracellular calcium
      observed with PPPn might stimulate these previously activated phospholipases.

PMID- 8743729
TI  - Enhanced expression of tissue factor activity in the atherosclerotic aortas of
      cholesterol-fed rabbits.
AB  - Tissue factor (TF) is an initiation cofactor of the extrinsic pathway of
      coagulation. Although the overexpression of TF antigen and mRNA have been
      previously demonstrated in atherosclerotic lesions using both immunohistochemical
      and in situ hybridization techniques, it still remains unclear as to whether TF
      activity is overexpressed in atherosclerotic plaque in vivo. In thoracic aortas
      obtained from cholesterol-fed rabbits for 10-20 weeks, the TF-mediated activation
      of factor X was quantitatively assessed on the intimal surface of the aortas ex
      vivo using a chromogenic substrate S-2222 and the findings were then compared
      with the immunohistochemical distribution of TF antigen. Non-atherosclerotic
      intimas showed only a weak amount of TF activity, while the adventitia contained
      a significantly high amount of activity. In the atherosclerotic intimas where TF
      antigen was overexpressed by foamy and non-foamy macrophages and smooth muscle
      cells but not by endothelial cells, TF activity was apparently enhanced to a
      level similar to that in the adventitia. Scanning electron microscopy revealed a
      perturbation of the intimal surface of the atherosclerotic aorta. These findings
      suggest that TF activity is apparently enhanced in subendothelial atherosclerotic
      lesions and, therefore, endothelial denudation, which results in the exposure of
      active TF to flowing blood, leads to thrombosis and its sequelae in
      atherosclerotic lesions.

PMID- 8743730
TI  - Antigenic properties of fibrinogen component of Hemaseel HMN subjected to the
      antiviral severe dry heat treatment.
AB  - The experiments in this work were focused on determination of the extent to which
      fibrinogen component of fibrin glue (Hemaseel HMN, Haemacure Biotech.) retained
      the conformation of the parent molecule after dry heat antiviral treatment (one
      hour at 100 degrees C). For this purpose antigenic structure of the fibrinogen
      component, heated and non-heated, was compared to that of control fibrinogens,
      i.e. the isolated one and the fibrinogen present in fresh human blood plasma. The
      analytic parameters CI50 and CIs were calculated from the competitive inhibition
      data obtained in ELISA systems using antisera to fibrinogen, plasmic fragments D
      and E, and to polypeptide chains A alpha, B beta, and gamma. These immunochemical
      analyses indicated that there was a modified expression of some fibrinogen
      epitopes probably resulting from unfolding of the A alpha chain and the better
      exposure of the E domain to the hydrated environment induced upon a heating
      procedure. Our data show that dry heat treatment of fibrinogen component is not
      associated with a significant overall conformational change of the molecule.

PMID- 8743731
TI  - Effects of a highly selective synthetic inhibitor of plasma kallikrein on
      disseminated intravascular coagulation in rats.
AB  - We found a new, highly selective plasma kallikrein inhibitor, trans-4-aminomethyl
      cyclohexanecarbonylphenylalanine 4-carboxymethylanilide hydrochloride, called
      PKSI-527 in our laboratories. This study was conducted to evaluate PKSI-527, on
      thromboplastin (TP)- and endotoxin (LPS)-induced disseminated intravascular
      coagulation (DIC) in rats. PKSI-527 was infused intravenously at 0.1 mg/kg/min
      for 250 min. Three of the parameters of the coagulation and fibrinolysis system,
      fibrinogen level, platelet counts and fibrin(ogen) degradation products (FDP)
      level were assayed. PKSI-527 prevented the change in the coagulation and
      fibrinolysis system in LPS-induced DIC, however it was not clearly effective in
      TP-induced DIC. The parameters of organ failure, such as serum glutamic
      oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), creatine
      phosphokinase (CPK), lactate, blood urea nitrogen and beta-glucuronidase, were
      assayed. Although the changes in the fibrinogen level, platelet counts and FDP
      level were almost the same in both models, the parameters of organ failure
      apparently increased in LPS-induced DIC more so than in TP-induced DIC. PKSI-527
      significantly suppressed the increases in GOT and GPT in LPS-induced DIC. These
      results indicate that plasma kallikrein may play a significant role in LPS
      induced DIC. Therefore, PKSI-527, as a synthetic plasma kallikrein inhibitor may
      be a valuable tool to explore the mechanism of DIC and the accompanying organ
      failure.

PMID- 8743732
TI  - Increased circulating plasminogen activator inhibitor-1 in patients with patent
      femoro-distal venous bypass.
AB  - Veins used for arterial bypass grafting undergo wall remodeling when exposed to
      altered flow, which may affect fibrinolytic mechanisms and subsequently the fate
      of the graft. Our aim was to study the extent of blood coagulation and
      fibrinolysis activation in 27 patients with patent grafts two years after femoro
      distal bypass surgery. The two matched control groups included 10 and 19
      conservatively treated patients having similar degree of arterial insufficiency
      (mean ankle/brachial blood pressure index) as the bypass group pre- and post
      operatively, respectively. Plasma samples for coagulation and fibrinolysis
      activation were determined using ELISA and chromogenic assays. When compared with
      the control groups circulating tissue-type plasminogen activator antigen, and
      especially plasminogen activator inhibitor type-1, PAI-1 antigen and activity
      were significantly increased, the mean increase ranging between 54% and 140% in
      the bypass group. Thrombin-antithrombin III complex, fibrinogen, and C-reactive
      protein, did not differ, while triglycerides were elevated in the bypass group.
      Ten patients in the bypass group were insulin resistant, but this did not explain
      the differences in the fibrinolytic parameters between the bypassed and control
      patients. Patients with peripheral vein grafts had upregulation of PAI-1 in their
      circulation implying reduced fibrinolytic capacity. Increased PAI-1, a risk
      factor for venous thrombosis, might reflect developing intimal hyperplasia, and
      it remains to be studied whether upregulation of PAI-1 in venous grafts
      associates with graft failure.

PMID- 8743733
TI  - Hippocampal lesions cause forgetting in a spatial response task.
AB  - Monkeys with lesions to the hippocampus and overlying cortex were impaired in
      making a spatially selective response on the basis of a spatial cue. Their
      impairment was even more severe on a task in which they were required to make
      spatial responses on the basis of cues which are not spatially distinct. A second
      experiment showed that once lesioned monkeys had been trained on a task with
      spatially distinct stimuli, they were initially able to perform accurately if the
      aspatial distinctiveness of the cue was reduced. However, their performance
      declined to chance over four to six trials. These results suggest that lesions to
      the hippocampus and overlying cortex may cause impairments in memory for the
      arrangement of visual scenes, including the spatial location of responses.
      KEYWORDS: spiny neurons, direct pathway, indirect pathways, rat neostriatum

PMID- 8743734
TI  - Synaptic connections between spiny neurons of the direct and indirect pathways in
      the neostriatum of the rat: evidence from dopamine receptor and neuropeptide
      immunostaining.
AB  - The flow of cortical information through the basal ganglia occurs through the so
      called 'direct pathway' and 'indirect pathways'. The object of the present work
      was to attempt to determine whether spiny neurons in the neostriatum that give
      rise to the direct pathway (i.e. the striatonigral/entopeduncular pathway) and
      those giving rise to the indirect pathways (i.e. striatopallidal pathway) are
      synaptically interconnected. The approach was to carry out double
      immunocytochemistry at the electron microscopic level using antibodies against
      peptides or dopamine receptor subtypes that are selectively associated with the
      neurons that give rise to the direct (substance P or D1 receptors) and indirect
      pathways (enkephalin or D2 receptors). Sections of perfuse-fixed rat neostriatum
      were immunostained to reveal both substance P immunoreactivity and D2 receptor
      immunoreactivity or enkephalin and D1 receptor immunoreactivity, respectively.
      Double peroxidase methods were employed using different chromogens that were
      distinguishable at both the light and electron microscopic levels. In the
      electron microscope substance P-immunoreactive terminals were seen in synaptic
      contact with dendritic structures that displayed immunoreactivity for D2
      receptor. Similarly, enkephalin-immunoreactive terminals were seen in synaptic
      contact with D1-immunoreactive dendritic structures. Thus, axon collaterals of
      neurons giving rise to the direct pathway form synaptic contacts with neurons
      that give rise to the indirect pathway and axon collaterals of neurons giving
      rise to the indirect pathway form synaptic contact with neurons that give rise to
      the direct pathway. These results indicate that the two pathways of information
      flow through the basal ganglia are synaptically linked at the level of the
      neostriatum. KEYWORDS: spiny neurons, direct pathway,indirect pathways, rat
      neostriatum

PMID- 8743735
TI  - Characterization of a distinctive motif of the low molecular weight neurotrophin
      receptor that modulates NGF-mediated neurite growth.
AB  - The cytoplasmic region of the common neurotrophin receptor (p75(NGFR)) (rat,
      human, chick) contains a putative membrane-associating domain implicated in
      intracellular signalling. A peptide (R3) identical to this domain (p75(NGFR) 367
      379) and various analogues of this peptide displayed circular dichroism spectra
      in aqueous and non-polar environments identical to the amphiphilic
      tetradecapeptide mastoparan (MP) and were internalized by PC12 rat
      pheochromocytoma cells. The R3 peptide enhanced neurite growth in PC12 cells,
      embryo chick primary sensory neurons and fetal rat primary sensory neurons in
      vitro in the presence of sub-saturating concentrations of NGF. Peptide analogues
      of R3 not faithful to the distance and angular relationships of ionic groups and
      the putative amphiphilic structure of p75(NGFR)367-379 displayed reduced potency
      to enhance p75(NGFR) (PC12(nnr5)), had no influence on neurite growth. The R3
      peptide had no effects on cell survival, cell binding or uptake of [125]NGF,
      affinity cross-linking of [125]NGF to p75(NGFR) or trkA monomers and homodimers,
      of NGF-mediated trkA monomer tyrosine phosphorylation. The studies implicate a
      role for a highly conserved motif of p75(NGFR) in the downstream modulation of
      NGF-mediated neurite growth.

PMID- 8743736
TI  - Muscarinic inhibition of glutamatergic transmissions onto rat magnocellular basal
      forebrain neurons in a thin-slice preparation.
AB  - We have examined excitatory and inhibitory transmission in visually identified
      rat magnocellular basal forebrain neurons using whole-cell patch-clamp recordings
      in a thin-slice preparation of the rat brain. In most cells, spontaneous
      excitatory and inhibitory synaptic activities could be recorded from their
      resting membrane potential. Following focal stimulation within the basal
      forebrain nucleus or directly onto visualized neighbouring neurons, postsynaptic
      currents were elicited in magnocellular basal forebrain cells held at -70 mb (a
      value close to their resting membrane potential). The synaptic responses were
      complex, consisting either mainly of excitatory postsynaptic currents (EPSCs), or
      inhibitory postsynaptic currents (IPSCs), or an EPSC-IPSC sequence. The EPSC
      component was consistent with the activation of AMPA/KA receptors, as it could be
      selectively blocked by CNQX. The IPSC component resulted in the activation of
      GAGAA receptors, and could be blocked by bicuculline. Since GABA-mediated
      trasmissions were not frequently recorded, we focused on the glutamate-mediated
      transmission. Studies using specific calcium channel blockers suggested that both
      omega-conotoxin GVIA-sensitive and omega-agatoxin VIA-sensitive calcium channels
      contribute to the glutamatergic transmission onto magnocellular basal forebrain
      neurons. Carbachol (0.3-30 microM) had no observable effect on holding current,
      but produced a dose-dependent inhibition of the amplitude of evoked EPSCs. This
      cholinergic modulation was mediated by muscarinic receptors, as it could be
      antagonized by atropine. The inhibitory effect of carbachol on the amplitude of
      EPSCs could be significantly antagonized by 100 nM methoctramine, an M2-receptor
      antagonist. In contrast, only a small degree of antagonism could be obtained with
      pirenzepine, and M1-muscarinic receptor antagonist, when present at relatively
      high concentration of 1 microM. Moreover, the action of carbachol was
      presynaptic, since the frequency of miniature postsynaptic currents was reduced
      without affecting their amplitude. In conclusion, the present findings indicate
      that glutamate-mediated transmission onto magnocellular basal forebrain neurons
      appeared to involve both N- and P/Q-type calcium channels, and that muscarinic
      modulation of glutamatergic transmission to MBF neurons is mediated by a
      presynaptic M2-muscarinic receptor subtypes.

PMID- 8743737
TI  - Neuronal differentiation in the rat hippocampus involves a stage-specific
      reorganization of subnuclear structure both in vivo and in vitro.
AB  - Pyramidal neurons from the hippocampus undergo a well characterized programme of
      differentiation in vitro involving five distinct stages (1-5). While some
      important aspects of the dynamic organization of cell cytoplasmic structure that
      underlie neuronal polarization have been elucidated, little is known about
      corresponding changes in nuclear organization. Here we identify major changes
      affecting nuclear structure and gene expression during late stages of
      differentiation. At stage 4 a sustained increase in global transcriptional
      activity occurs. This is followed at stage 5 by proliferation of coiled bodies,
      i.e. subnuclear organelles containing splicing factors, which form a novel domain
      around the nucleus that we refer to as the rosette. Both the morphology and
      timing of rosette formation are identical in neurons in vitro and in situ in the
      developing hippocampus in rat brain. Long-term synaptic inhibition in vitro or
      growth at low density does not prevent either nuclear reorganization, enhanced
      transcriptional activity or the formation of pre-synaptic specializations. These
      data indicate that stage-specific changes in nuclear structure and function,
      similar to distinct rearrangements of cytoplasmic components, are pre-programmed
      aspects of the neuronal differentiation pathway in the hippocampus.

PMID- 8743738
TI  - Cranial motor axons respond differently to the floor plate and sensory ganglia in
      collagen gel co-cultures.
AB  - Within the developing chick hindbrain, motor neurons differentiate in columns on
      either side of the ventral midline floor plate. Along the rostrocaudal axis,
      populations of motor neurons are organized segmentally with the trigeminal (V)
      and facial (VII) nuclei occupying successive pairs of rhombomeres. To reach their
      targets, motor axons follow stereotyped pathways. Branchiomotor and visceral
      motor axons of the Vth and VIIth nerves first project in a dorsal (lateral)
      direction away from the floor plate and towards the nerve exit point located in
      the alar plate of the even-numbered rhombomere of the pair. Having exited the
      hindbrain, axons grow in association with the cranial sensory ganglia before
      branchiomotor axons enter the branchial arches. We have investigated some of the
      factors that might guide cranial motor axons using a three-dimensional collagen
      gel culture system. When explants of hindbrain basal plate containing trigeminal
      or facial motor neurons were co-cultured with floor plate explants, axon
      outgrowth from the side facing the floor plate was inhibited in a manner
      consistent with chemorepulsion. When basal plate explants that contained an exit
      point were cultured alone, motor axons grew to the exit point and then stopped.
      When basal plate explants were co-cultured with trigeminal ganglia, motor
      outgrowth was increased in comparison with that in control cultures, suggesting a
      trophic influence. The findings presented here indicate that motor pathways are
      elaborated due to a progression of signals to which the growth cones respond in
      sequence.

PMID- 8743739
TI  - Chronic dizocilpine maleate (MK-801) treatment suppresses the effects of
      nigrostriatal dopamine deafferentation on enkephalin but not on substance P
      expression in the rat striatum.
AB  - The present study examined the effects of chronic treatment with dizocilpine
      maleate (0.2 mg/kg i.p., twice a day for 8 days) alone or in combination with
      unilateral 6-hydroxydopamine-induced lesion of the nigrostriatal dopaminergic
      neurons on substance P and enkephalin expression in the rat striatum. This was
      done by means of quantitative in situ hybridization histochemistry and
      immunocytochemistry. As reported previously, the unilateral dopaminergic lesion
      resulted in marked decreases in substance P mRNA expression and immunoreactivity
      in the ipsilateral striatum while enkephalin mRNA expression and Met-enkephalin
      immunoreactivity were considerably increased in this structure. Blockade of NMDA
      receptors by chronic dizocilpine maleate treatment alone resulted in decreased
      levels of striatal substance P mRNA without significant change in substance P
      immunoreactivity versus controls. Enkephalin mRNA levels were also decreased in
      the striatum, matched by parallel reductions in Met-enkephalin immunoreactivity.
      These observations indicate that NMDA receptor activity may exert tonic
      excitatory effects on substance P and enkephalin expression in the striatum. The
      same chronic treatment with dizocilpine maleate started 12 days after the 6
      hydroxydopamine injection suppressed the lesion-induced up-regulation of
      enkephalin expression without significantly affecting the down-regulation of
      substance P expression. These data provide evidence that NMDA receptor-mediated
      mechanisms contribute to the alteration of striatal enkephalin expression
      associated with dopaminergic depletion in hemiparkinsonian rat models.

PMID- 8743740
TI  - Contrasting effects of chronic clozapine, Seroquel(TM) (ICI 204,636) and
      haloperidol administration of deltaFosB-like immunoreactivity in the rodent
      forebrain.
AB  - We have recently demonstrated that specific neuroanatomical patterns of Fos-like
      immunoreactivity are predictive of atypical antipsychotic activity. However, the
      fact that neuroleptics must be administered chronically in order to generate both
      extrapyramidal side effects and an optimal therapeutic response calls into
      question the relevance of acute changes in Fos-like immunoreactivity for these
      slowly developing events. Fos-like immunoreactivity cannot be used to identify
      neurons activated by chronic neuroleptic administration because the increase in
      Fos-like immunoreactivity produced by an acute antipsychotic injection is
      dramatically reduced following repeated neuroleptic administration. In contrast,
      expression of the immediate-early gene product deltaFosB is persistently elevated
      in the striatum by chronic haloperidol administration. This suggests that
      deltaFosB-like immunoreactivity may be used to identify neurons activated by
      chronic antipsychotic administration. Since typical and atypical neuroleptics
      elevate Fos-like immunoreactivity in different regions of the forebrain acutely,
      the purpose of the present study was to determine whether typical (haloperidol)
      and atypical (clozapine, ICI 204,636) antipsychotics produce distinct patterns of
      elevated deltaFosB-like immunoreactivity in the forebrain after chronic
      administration. Administration of haloperidol (2 mg/kg/day) to rats for 19 days
      induced a homogeneous elevation of neurons which displayed deltaFosB-like
      immunoreactivity in the ventral, medial and dorsolateral aspects of the striatum.
      Chronic haloperidol administration did not enhance the deltaFos-like
      immunoreactivity in the prefrontal cortex and lateral septal nucleus. Repeated
      administration of clozapine (20 mg/kg/day) and ICI 204,636 (20 mg/kg/day) for 19
      days elevated deltaFosB-like immunoreactivity not only in the ventral striatum
      but also in the prefrontal cortex and lateral septal nucleus. However, these
      compounds had weak effects on deltaFosB-like immunoreactivity in the dorsolateral
      striatum. These results suggest that a preferential action on limbic structures
      such as the prefrontal cortex, ventral striatum and lateral septal nucleus may
      account for the ability of chronic clozapine and ICI 204, 636 administration to
      reduce the symptoms of schizophrenia without generating extrapyramidal side
      effects.

PMID- 8743741
TI  - Brain rhythms of language: nouns versus verbs.
AB  - Electrocortical activity was recorded from scalps of human subjects reading nouns
      and verbs. Current source density analysis of EEG signals and calculation of
      spectral responses revealed differences between word categories in the 30 Hz
      range. Verbs elicited stronger 30 Hz activity at recording sites over the motor
      cortices, while nouns elicited stronger responses at sites over visual cortices
      in the occipital lobes. Behavioural testing indicated that, at the cognitive
      level, this double dissociation corresponds to motor and visual associations
      prompted by verbal stimuli. These results suggest that local high-frequency brain
      responses can be indicators of conscious processing of motor and visual
      associations of verbal material. Furthermore, the results provide additional
      evidence that nouns and verbs have distinct neuronal generators in the intact
      human brain.

PMID- 8743742
TI  - Synaptogenesis in the occipital cortex of macaque monkey devoid of retinal input
      from early embryonic stages.
AB  - The role of input from the retina on the development of synaptic organization in
      the primate striate cortex was examined in macaque monkeys enucleated at
      embryonic (E) day 67 and E59. Both the prenatally operated animals and their age
      matched controls were delivered at term (E165) and killed either at 3 months (at
      the end of the rapid phase of synaptogenesis) or 3 years (at the end of the
      plateau phase of synaptogenesis). As expected, in the operated animals the
      striate cortex had a smaller surface area but a normal thickness and complement
      of layers. The present study revealed that the mean densities of synaptic
      contacts per unit area and volume of neuropil in the striate cortex of the two
      operated animals were similar to those of age-matched controls (approximately
      30/100 microm2 or 100/100 microm3 of neuropil). Thus, the absence of retinal
      input via the lateral geniculate nucleus did not affect the schedule and
      magnitude of synaptogenesis. Likewise, the ratio of symmetrical versus
      asymmetrical synapses and mean lengths of synaptic junctions were within the
      normal range of variation in both group of animals. The proportions of synaptic
      contacts situated on dendritic spines and shafts were also similar in supra- and
      infragranular cortical layers of normal and enucleated animals. However, the
      ratio of synapses situated on dendritic spines and shafts in the sublayers IVAB
      and IVC, which normally become reversed during late adolescence, were not
      reversed in the enucleates. Therefore, our study indicated that certain
      parameters of synaptic development, such as the density of contacts per unit
      volume of neuropil and the proportion of basic types and their size, in the supra
      and infragranular layers of the striate cortex develop to an optimal normal
      level in the absence of both retinae from early embryonic stages. However, in the
      thalamorecipient sublayers the details of the synaptic circuits such as their
      localization on dendritic spines or shafts, fail to mature properly in the
      absence of normal functional input from the periphery.

PMID- 8743743
TI  - Involvement of Na+-Ca2+ exchanger in reperfusion-induced delayed cell death of
      cultured rat astrocytes.
AB  - In some cells, Ca2+ depletion induces an increase in intracellular Ca2+ ([Ca2+]i)
      after reperfusion with Ca2+-containing solution, but the mechanism for the
      reperfusion injury is not fully elucidated. Using an antisense strategy we
      studied the role of the Na+-Ca2+ exchanger in reperfusion injury in cultured rat
      astrocytes. When astrocytes were perfused in Ca2+-free medium for 15-60 min, a
      persistent increase in [Ca2+]i was observed immediately after reperfusion with
      Ca2+-containing medium, and the number of surviving cells decreased 3-5 days
      later. The increase in [Ca2+]i was enhanced by low extracellular Na+ ([Na+]0)
      during reperfusion and blocked by the inhibitors of the Na+-Ca2+ exchanger
      amiloride and 3, 4-dichlorobenzamil, but not by the Ca2+ channel antagonists
      nifedipine, Ca2+ and Ni2+. Treatment of astrocytes with antisense, but not sense,
      oligodeoxynucleotide to the Na+-Ca2+ exchanger decreased Na+-Ca2+ exchanger
      protein level and exchange activity. The antisense oligomer attenuated
      reperfusion-induced increase in [Ca2+]i and cell toxicity. The Na+-Ca2+ exchange
      inhibitors 3, 4-dichlorobenzamil and ascorbic acid protected astrocytes from
      reperfusion injury partially, while the stimulators sodium nitroprusside and 8
      bromo-cyclic GMP and low [Na+]0 exacerbated the injury. Pretreatment of
      astrocytes with ouabain and monensin caused similar delayed glial cell death.
      These findings suggest that Ca2+ entry via the Na+-Ca2+ exchanger plays an
      important role in reperfusion-induced delayed glial cell death.

PMID- 8743744
TI  - Activation of meningeal 5-HT2B receptors: an early step in the generation of
      migraine headache?
AB  - Several pharmaceuticals are frequently dispensed to prevent or reduce the
      occurrence of migraine attacks. The prophylactic effect of these drugs has been
      suggested to be caused through blockade of serotonin (5-HT) receptors of type 5
      HT2B or 5-HT2C. To elucidate which of these receptors is involved, we first used
      radioligand binding assays to determine the pharmacological profile of the human
      and rat-5-HT2B receptor. Furthermore, the potency of drugs used in migraine
      prophylaxis to stimulate or inhibit 5-HT2B or 5-HT2C receptor-mediated potency of
      drugs used in migraine prophylaxis to stimulate or inhibit 5-HT2B or 5-HT2C
      receptor-mediated phosphatidyl inositol hydrolysis was measured. All these drugs
      were found to block both human receptors. Correlation of the receptor affinities
      with the potencies used in migraine prophylaxis showed significant correlations,
      which were better for the 5-HT2B (P = 0.001) than for the 5-HT2C receptor (P =
      0.005). Migraine headache is thought to be transmitted by the trigeminal nerve
      from the meninges and their blood vessels. Using the reverse transcription
      polymerase chain reaction, the expression patterns of all cloned G-protein
      coupled serotonin receptors were analysed in various human meningeal tissues. All
      tissues expressed 5-HT1Dbeta, 5-HT2A, 5-HT2B, 5-HT4 and 5-HT7 mRNAs. Only trace
      amounts of 5-HT2C receptor mRNA were found. With organ bath experiments we showed
      that the 5-HT2B receptor stimulated the relaxation of the pig cerebral artery via
      the release of nitric oxide. Our data support the hypothesis that 5-HT2B
      receptors located on endothelial cells of meningeal blood vessels trigger
      migraine headache through the formation of nitric oxide.

PMID- 8743745
TI  - Post-translational processing of the alternative neuropeptide precursor encoded
      by the FMRFamide gene in the pulmonate snail Lymnaea stagnalis.
AB  - The neuropeptide gene encoding FMRFamide-like peptides in the pulmonate mollusc
      Lymnaea is subject to alternative splicing that generates cell-specific
      expression of distinct sets of peptides in the CNS. In this paper, we analyse the
      post-translational processing of the alternative protein precursor encoded by the
      exon I, III-V transcript (type 2 transcript). We raised anti-peptide antisera
      specific to distinct segments of the precursor in order to address the pattern of
      endoproteolytic cleavages, specifically around the tetrabasic site RRKR. We first
      showed that not all peptides predicted by the precursor structure are generated
      as final steady-state products. We then identified a novel peptide by biochemical
      purification, amino acid sequencing and mass spectrometry- the 35 amino acid
      SDPFFRFGKQQVATDDSGELDDEILSRVSDDDKNI, which we termed the acidic peptide,
      previously not predicted on the basis of the precursor structure. This novel
      peptide, abundant in the snail brain (0.7 pmol per central nervous system),
      includes the N-terminal sequence SDPFFRF, which was previously considered to be a
      variant of the known heptapeptide SDPFLRFamide, also encoded within the same
      protein precursor. We showed by in situ hybridization and immunocytochemistry
      that the acidic peptide is produced in all cells that transcribe type 2 FMRFamide
      mRNA. We mapped the expression of this novel peptide in the CNS and localized it
      mainly in three identifiable neuronal clusters - the E, F and B groups of cells -
      and some additional neurons, all situated in three of the eleven central ganglia.
      Immunoreactive neurons included the single identifiable visceral white
      interneuron (VWI or VD4), a key cell of the cardiorespiratory network.

PMID- 8743746
TI  - Origin of aspartate-induced responses in rat cerebellar Purkinje cells.
AB  - The effects of glutamate, aspartate and N-methyl-D-aspartate (NMDA) on Purkinje
      cells and interneurons were investigated in cerebellar slice cultures using the
      whole-cell configuration of the patch-clamp technique. L-Glutamate and L
      aspartate induced inward currents in Purkinje cells voltage-clamped at -60 mV. In
      standard external solution, the amplitude of the responses induced by the two
      amino-acids was a linear function of the membrane potential. L-Aspartate-induced
      currents were inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a
      selective antagonist of non-NMDA receptors. NMDA, a selective agonist of NMDA
      receptors, had no effect of its own on the excitability of Purkinje cells, but
      was effective in blocking the responses induced by aspartate in Purkinje cells in
      a voltage-independent manner. In contrast, D-(-)-2-amino-5-phosphonovaleric acid
      (D-APV), a selective antagonist of NMDA receptors, had no effect on aspartate
      induced responses. D-Aspartate also induced responses in Purkinje cells, and the
      amplitude of these responses was a linear function of the membrane potential.
      Currents induced by L- and D-aspartate were inhibited by dihydrokainate, a
      glutamate uptake blocker. In sodium-free external solution, glutamate still
      induced outward currents in Purkinje cells, whereas L- and D-aspartate no longer
      evoked any current. When sodium was replaced by lithium in the external medium,
      no change in the holding current could be detected in Purkinje cells maintained
      at -60 mV; moreover, in this bathing medium L-aspartate no longer evoked any
      current whereas glutamate-induced responses were still present. In contrast,
      interneurons were sensitive to both NMDA and aspartate applications, and these
      responses were antagonized by D-APV. In addition, aspartate still induced an
      outward current in sodium-free external solution. This study presents rather
      direct evidence in favour of L-aspartate as being a very selective NMDA receptor
      agonist in the cerebellum. L-Aspartate-induced currents in Purkinje cells are not
      due to activation of mixed NMDA/non-NMDA receptors, but are probably due to the
      release of L-glutamate induced by aspartate through glutamate uptake.

PMID- 8743747
TI  - Chromogranin mRNA levels in the brain as a marker for acute and chronic changes
      in neuronal activity: effect of treatments including seizures, osmotic
      stimulation and axotomy in the rat.
AB  - Chromogranin/secretogranins are a family of acidic, soluble proteins with a
      widespread distribution in secretory vesicles of endocrine and nervous tissues.
      The effects of experimental stimuli of differing duration and intensity on
      chromogranin B and secretogranin II mRNA levels in relevant areas of the rat
      brain were examined by in situ hybridization histochemistry using 35S-labelled
      oligonucleotides. Effects of two 'chronic stimulation' paradigms were studied -
      the effect of 4 days of water or food deprivation on mRNA levels in the
      hypothalamus and the effect of unilateral cervical vagotomy on transcript levels
      in the dorsal vagal complex 1, 2 and 7 days after surgery. After 4 days of water
      deprivation secretogranin II mRNA was significantly increased in supraoptic
      nucleus (366 +/- 21% of control, P < 0.01), the magnocellular paraventricular
      nucleus (209 +/- 20% of control, P < 0.01) and the parvocellular paraventricular
      nucleus (147 +/- 6% of control, P < 0. 05) after 4 days of food deprivation.
      Seven days after unilateral cervical vagotomy, secretogranin II and chromogranin
      B mRNA levels were markedly decreased in the ipsilateral dorsal motor nucleus of
      the vagus (25 +/- 4 and 47 +/- 8% of contralateral values respectively, P <
      0.01). Rapid changes in chromogranin mRNA were also detected following shorter
      duration 'acute stimulation' - in the hypothalamus after hypertonic saline
      injection, in the hippocampus after electrical stimulation-induced kindled
      seizures, and in the cerebral cortex after unilateral craniotomy. A large
      increase in secretogranin II mRNA was detected in the supraoptic nucleus (202 +/-
      25% of control, P < 0.01) and the magnocellular paraventricular nucleus (168 +/-
      29% of control, P < 0.05) 3 h after a single intraperitoneal injection of
      hypertonic (1.8 M) saline. Markedly increased levels of secretogranin II (125
      160% of control) and chromogranin B (140-230% of control) mRNA were observed in
      granule cells of the dentate gyrus 0.5-2 h after amygdaloid stimulation-induced
      seizures. A moderate increase in secretogranin II mRNA (144 +/- 11% of
      contralateral side, P < 0.01) was found in the underlying cerebral cortex 2.5 h
      after unilateral craniotomy. These results indicate that measurement of changes
      in chromogranin mRNA, particularly secretogranin II, is a useful means of
      assessing both rapid and long-lasting increases and decreases in neuronal
      activity and, in contrast to immediate early gene mRNA levels, may better reflect
      specific changes in neuronal secretory activity associated with
      transmitter/peptide release.

PMID- 8743748
TI  - Differential frequency conditioning enhances spectral contrast sensitivity of
      units in auditory cortex (field Al) of the alert Mongolian gerbil.
AB  - Differential aversive auditory conditioning in the awake Mongolian gerbil was
      performed during single- and multi-unit recording in field Al of the primary
      auditory cortex. Presentations of pure tone stimuli of a given frequency
      (reinforced conditioned stimulus; CS+) paired with electrocutaneous stimulation
      (unconditioned stimulus) were combined with several other non-reinforced tone
      stimuli (non-reinforced conditioned stimulus; CS-). Stimulus presentation during
      training and testing was optimized for constancy of the probability of occurrence
      of both the CS+ and the CS- stimulus. The paradigm led to a reorganization of
      both the spectral and temporal response characteristics of auditory cortical
      neurons with the following basic results. First, tone-evoked responses of Al
      neurons recorded after multiple acoustic stimulation under these conditions
      varied statistically around a mean value (stationarity). Conditioning produced a
      shift in mean values of evoked responses. The altered tone responses were also
      stationary (stability of the plastic effects). Second, the frequency-receptive
      fields (FRFs) of neurons were reorganized in a frequency-specific way such that
      the CS+ frequency became located in a local minimum of the FRF after training.
      This resulted from a training-induced increase in the responses to frequencies
      adjacent to the CS+ frequency in the FRF relative to the CS+ response. The effect
      can be interpreted as an enhancement of the 'spectral contrast' sensitivity of
      the unit in the CS+ neighbourhood. Third, apart from this frequency-specific
      plastic effect, responses to other frequencies also underwent changes during
      training. The non-frequency-specific changes were not generally predictable but
      the post-trial responses were stationary. Fourth, the analysis of the long-term
      behaviour of FRF reorganization revealed the stability of plastic effects under
      retention training and the gradual re-establishment of the pretrial FRF during
      extinction training. Fifth, not only the spectral characteristics but also the
      temporal structure of the tone-evoked responses could be affected by the
      training. In most cases the training-induced changes measured within the first
      tens of milliseconds of the response corresponded to the response changes
      obtained by integration over the total response period. There were some cases,
      however, in which the direction of the response change varied with time,
      indicating that excitatory and inhibitory influences on the temporal response
      pattern were differently affected by training.

PMID- 8743749
TI  - Increased expression of BDNF and trkB mRNA in rat facial motoneurons after
      axotomy.
AB  - Motoneurons of the adult survive after axotomy even though they are deprived of
      putative target derived trophic factors. Alternative sources of trophic support
      may substitute. In this study we test the hypothesis that the immediate
      environment of the motoneuronal cell body or the cell body itself increases the
      production of trophic factors after axonal injury. Using in situ hybridization
      (ISH) and reverse transcription-polymerase chain reaction (RT-PCR), we report
      that after axotomy, rat facial motoneurons increase the expression of mRNA for
      brain-derived neurotrophic factor (BDNF) and its receptor trkB. After transection
      of the facial nerve, we measured a 2- to 4-fold increase in BDNF mRNA expression
      which had its onset between 3 and 8 h after injury. The BDNF mRNA levels peaked
      at approximately 1-2 days and gradually declined thereafter to return to
      contralateral levels within 7 days of injury. Western blotting revealed a several
      fold increase in BDNF as early as 24 h, which subsequently reached a maximum in
      approximately 5-7 days and was still sustained at 2 weeks post-axotomy. Using
      exon-specific primers, we determined that the increase in BDNF mRNA is largely
      due to an increased expression from the promoters of exons IV and III, and to a
      lesser extent from exons I and II. Analysing the mRNA expression for the BDNF
      receptor, trkB, we found a 2- to 3-fold increase in full-length trkB mRNA
      expression starting 2 days after axotomy which lasted 2-3 weeks. These findings
      suggest that BDNF might act locally on axotomized motoneurons in an autocrine
      fashion, providing support for axotomized motoneurons during the first weeks
      after axotomy.

PMID- 8743750
TI  - Effects of substance P on medial vestibular nucleus neurons in guinea-pig
      brainstem slices.
AB  - The undecapeptide substance P (SP) has been recently implicated in the control of
      vestibular function. In particular, it seems to be co-localized with glutamate in
      approximately half of the primary vestibular afferents in mammals. Using
      intracellular recordings in guinea-pig brainstem slices, we have investigated the
      effects of SP and of several agonists of the three known tachykinin receptor
      subtypes (NK1, NK2 and NK3) on the three main types (A, B and B+LTS) of guinea
      pig medial vestibular nucleus neurons (MVNn) that we had previously described. SP
      could induce two distinct kinds of effects on all types of MVNn. Whereas around
      half of them were depolarized and had their membrane resistance increased by SP,
      approximately 10% of all MVNn were in contrast hyperpolarized and inhibited while
      their membrane resistance was decreased. Both responses persisted under
      conditions of blockade of synaptic transmission, and were thus due to the
      activation of postsynaptic binding sites. The SP-induced membrane depolarization
      could not be reproduced with any one of the specific agonists of the three
      tachykinin receptor subtypes, nor was it blocked by the specific NK1 receptor
      antagonists GR 82664 and CP 99994. This effect might therefore be due to the
      activation of a new, pharmacologically distinct, 'NK1-like' receptor. Only the
      hyperpolarizing effects, which were in contrast mimicked by the specific NK1
      receptor agonists GR 73632 and [Sar9, Met (O2)11]-SP, would be mediated by the
      few typical NK1 receptors which have been demonstrated in the medial vestibular
      nucleus.

PMID- 8743751
TI  - Emx1 and Emx2 show different patterns of expression during proliferation and
      differentiation of the developing cerebral cortex in the mouse.
AB  - Insights into the complex structure of the forebrain and its regulation have
      recently come from the analysis of the expression of genes that are likely to be
      involved in regionalization of this structure. We cloned four new homeo box
      genes, Emx1, Emx2, Otx1 and Otx2, and showed that in day 10 mouse embryos their
      expression domains are continuous regions of the developing brain contained
      within each other in the sequence Emx1 < Emx2 < Otx1 < Otx2. Recently Otx1 has
      been found to be specifically expressed during neurogenesis of layer 5 and 6 in
      the developing cerebral cortex. In order to better understand the role of Emx1
      and Emx2 in the maturation of the cortex we analysed by in situ hybridization
      their expression patterns in the developing mouse cerebral cortex, from embryonic
      day 12.5 to adulthood. We found that Emx2 is expressed exclusively in
      proliferating cells of the ventricular zone whereas Emx1 is expressed in both
      proliferating and differentiated neurons, throughout the cortical layers and
      during all the developmental stages examined. Therefore, Emx2 gene products might
      control some biological parameters of the proliferation of cortical neuroblasts
      or of the subsequent cell migration of postmitotic neurons, leaving the cortical
      germinal zone. Conversely, Emx1 expression, which is confined exclusively to the
      dorsal telencephalon, characterizes most cortical neurons during proliferation,
      differentiation, migration and postnatal development and maturation.

PMID- 8743752
TI  - Topographically organized climbing fibre sprouting in the adult rat cerebellum.
AB  - Adaptive recovery following brain injury requires the topography of projection
      maps to be restored. In the adult mammalian brain, the regeneration of severed
      axons does not normally occur and repair mainly relies on collateral
      reinnervation from uninjured neurons. Although reinnervation can be target
      specific at the single cell level, it is not known if the new connections are
      organized correctly. The normal olivocerebellar projection had precise topography
      in which subnuclei of the inferior olive terminate as climbing fibres on
      chemically defined bands of cerebellar Purkinje cells. This precision has been
      exploited to determine the topography of climbing fibre sprouting following an
      inferior olive lesion in the adult rat. Collateral reinnervation was found to
      respect the boundaries between the Purkinje cell compartments. Thus,
      topographical cues are available in the adult during post-lesion plasticity to
      guide the restoration of the olivocerebellar projection map.

PMID- 8743753
TI  - Evidence for direct connections between the hand region of the supplementary
      motor area and cervical motoneurons in the macaque monkey.
AB  - In primates the corticospinal neurons of the hand representation of the primary
      motor cortex (M1) give rise to direct contacts with the cervical motoneurons that
      control distal forelimb muscles. We investigated, at the light-microscopy level,
      whether corticospinal cells present in the hand area of the supplementary motor
      area (SMA) also establish direct connections with cervical motoneurons,
      particularly those innervating hand and finger muscles. The hand representation
      of the M1 (two monkeys) or SMA (two monkeys) was located using intracortical
      microstimulation and injected with the anterograde tracer biotinylated dextran
      amine to label corticospinal terminals. Forearm muscles acting on the wrist and
      hand as well as hand muscles acting on the thumb and index finger, thus including
      those activated by intracortical stimulation, were injected with the retrograde
      tracer cholera-toxin B subunit, in order to label the motoneurons. A consistent
      zone of overlap between the two markers was found in the cervical cord. Close
      appositions between corticospinal axonal terminals and the somata or dendrites of
      motoneurons were found after injection in the M1, confirming previous
      observations. The new finding is the observation of similar close appositions
      after injection in the SMA, suggesting its control of hand movements in parallel
      with the M1.

PMID- 8743754
TI  - Early postoperative rise in defibrillation threshold in patients with
      nonthoracotomy defibrillation lead systems: attenuation with biphasic shock
      waveforms.
AB  - INTRODUCTION: In patients with non-thoracotomy defibrillation lead (NTL) systems
      coupled with monophasic shock waveforms, the defibrillation threshold (DFT) rises
      early after implantation. There is little information regarding features
      predictive of the DFT rise, or DFT changes early after implantation of NTL
      systems coupled with biphasic shock waveforms. METHODS AND RESULTS: DFT
      measurements were performed serially at implantation, prior to hospital discharge
      (mean 4 +/- 3 days), and at follow-up (mean 49 +/- 22 days) in 146 patients with
      an NTL system. Factors were assessed for association with a "clinically
      important" early postimplantation DFT rise, defined as a rise of > or = 2 energy
      steps (2 to 4 J per step; > or = 5 J total). A clinically important early
      postimplantation DFT rise occurred in 48 patients (33%). Univariate predictors of
      the rise included the monophasic shock waveform, the Medtronic Transvene lead
      system, the presence of a subcutaneous defibrillation patch, and the number of
      shocks delivered during the implantation procedure. However, the only independent
      predictor of a clinically important DFT rise was the monophasic shock waveform (F
      = 18, P < 0.001). For the monophasic patient group (n = 79), the incidence of a
      DFT rise was 53% (n = 42). For the biphasic patient group (n = 67), the incidence
      of a DFT rise was 9% (n = 6). The clinical characteristics of the monophasic and
      biphasic groups were not significantly different, nor were their DFTs at
      implantation. Among a subgroup of 18 consecutive patients who underwent serial
      DFT testing utilizing both monophasic and biphasic waveforms, the incidence of a
      clinically important DFT rise with monophasic (n = 9,50%) was higher than with
      biphasic shocks (n = 3,17%; P = 0.05). CONCLUSION: NTL systems coupled with
      biphasic shock waveforms have an attenuated incidence of a clinically important
      DFT rise early after implantation, relative to patients with NTL systems coupled
      to monophasic waveforms.

PMID- 8743755
TI  - The mechanisms responsible for lack of reproducible induction of atrioventricular
      nodal reentrant tachycardia.
AB  - INTRODUCTION: AV nodal reentrant tachycardia (AVNRT) is not always reproducibly
      inducible. The purpose of this study was to determine the mechanisms responsible
      for the lack of reproducible induction of AVNRT. METHODS AND RESULTS: The
      induction of AVNRT was assessed with atrial burst pacing, and with atrial and
      ventricular programmed stimulation, each with one and two extrastimuli, in 103
      patients with AVNRT. The stimulation protocol was repeated 10 times in the
      baseline state, during isoproterenol infusion, and after atropine administration,
      or until AVNRT was induced in 7 of 10 attempts. The mechanisms responsible for <
      7 of 10 inductions were classified as: (1) the inability to achieve critical AH
      prolongation; (2) fast pathway block; and (3) slow pathway block. The induction
      endpoint was achieved in 90 patients: 55 in the baseline state, 34 during
      isoproterenol infusion, and 1 after atropine. The mechanism of noninducibility in
      the baseline state (n = 48) was the inability to achieve a critical AH interval
      in 20%, fast pathway block in 49%, and slow pathway block in 31% (P = 0.02).
      During isoproterenol administration (n = 14) and after atropine administration (n
      = 13), the three mechanisms were equally responsible for nonreproducible
      induction of AVNRT. CONCLUSIONS: The induction of AVNRT is poorly reproducible in
      approximately 10% of patients. In the baseline state, the most common reason for
      the inability to reproducibly induce AVNRT is fast pathway block. In the presence
      of isoproterenol or atropine, each of the three mechanisms was equally
      responsible for noninducibility of AVNRT.

PMID- 8743756
TI  - Evidence for the presence of M cells in the guinea pig ventricle.
AB  - INTRODUCTION: Recent studies have described the presence of M cells in the deep
      layers of the canine and human ventricle displaying electrophysiologic and
      pharmacologic features different from those of epicardial (EPI) and endocardial
      (ENDO) cells. The M cell is distinguished electrophysiologically by the ability
      of its action potential to prolong disproportionately to that of other myocardial
      cells with slowing of the stimulation rate and pharmacologically by its unique
      sensitivity to Class III antiarrhythmic agents. The present study was designed to
      test the hypothesis that similar cells are present in the guinea pig ventricle.
      METHODS AND RESULTS: We used a dermatome to obtain-thin strips of left
      ventricular free wall from the hearts of guinea pigs (8 to 14 weeks old) and
      standard microelectrode techniques to record transmembrane activity. Action
      potential duration measured at 90% repolarization (APD90) was significantly
      longer in mid-myocardial (MID) cells than in surface EPI or ENDO cells at all
      basic cycle lengths (BCLs) tested. At a BCL of 300 msec, APD90 was 102 +/- 21,136
      +/- 9, and 95 +/- 15 msec in EPI, MID, and ENDO cells (mean +/- SD; n = 12). At a
      BCL of 5000 msec, APD90 was 133 +/- 14, 185 +/- 24, and 135 +/- 13 msec in EPI,
      MID, and ENDO cells ([K+]o = 4 mM). Thus, APD-rate relations were more pronounced
      in the MID cells. MID cells were also more sensitive to agents with Class III
      actions (e.g., d,I-sotalol: 10 to 100 microM), exhibiting a greater APD
      prolongation than EPI or ENDO. d,I-Sotalol also induced early
      afterdepolarizations in MID cells but not in EPI or ENDO cells. The rate of rise
      of the action potential upstroke (Vmax) was significantly greater in MID cells:
      129 +/- 13, 240 +/- 42, and 192 +/- 28 V/sec in EPI, MID, and ENDO cells (n = 10
      to 18). CONCLUSION: Our results demonstrate the existence of important transmural
      electrical heterogeneity in guinea pig ventricular myocardium. The study provides
      data in support of the existence of M cells in the mid-myocardial layers of the
      guinea pig ventricle exhibiting longer APDs and a greater sensitivity to agents
      with Class III antiarrhythmic action.

PMID- 8743757
TI  - Activation and repolarization patterns are governed by different structural
      characteristics of ventricular myocardium: experimental study with voltage
      sensitive dyes and numerical simulations.
AB  - INTRODUCTION: Substantial progress has been made in our understanding of
      transmural activation across ventricular muscle through studies of excitation
      patterns and potential distributions. In contrast, repolarization sequences are
      poorly understood because of experimental difficulties in mapping action
      potential durations (APDs) using extracellular electrodes. METHODS AND RESULTS:
      Langendorff-perfused guinea pig hearts and isolated coronary-perfused left
      ventricular sheet preparations were stained with the voltage-sensitive dye RH-421
      and optical APs were recorded with a photodiode array. Epicardial maps were
      constructed using a triangulation method applied to matrices of activation and
      repolarization times determined from (dF/dt)max and (d2F/dt2)max' respectively.
      Numerical simulations were carried out based on: (1) a modified Luo-Rudy model;
      (2) the three-dimensional architecture of ventricular fibers; and (3) the
      intrinsic spatial distribution of APDs. In ventricular sheets, epicardial
      stimulation elicited elliptical activation patterns with the major axis aligned
      with the longitudinal axis of epicardial fibers. When the pacing electrode was
      progressively inserted from epicardium to endocardium, the major axes rotated
      gradually, clockwise by 45 degrees, and the eccentricity decreased from 2 to
      1.14. Repolarization showed a relatively uniform pattern, independent of pacing
      site, beginning at the apex and spreading to the base. CONCLUSION: In experiments
      and simulations, the helical rotation of epicardial excitation isochrones caused
      by pacing at increasing depth in the myocardium correlated with the helical three
      dimensional architecture of ventricular fibers. In contrast, repolarization was
      independent of the activation sequence and was mainly guided by spatial
      differences in APDs between apex and base.

PMID- 8743758
TI  - A new technique to perform epicardial mapping in the electrophysiology
      laboratory.
AB  - INTRODUCTION: A possible epicardial site of origin may be the reason for
      unsuccessful endocardial application of radiofrequency energy to control
      recurrent ventricular tachycardia. This study tests the feasibility and safety of
      a new epicardial mapping technique in patients with Chagas' disease and recurrent
      ventricular tachycardia. METHODS AND RESULTS: Epicardial mapping was performed
      through a pericardial puncture as an epidural introducer needle was advanced into
      the pericardial space under fluoroscopic guidance. Medium contrast was injected
      to demonstrate the position of the needle tip, and a guidewire was introduced
      until its tip lay within the pericardial space. A 8-French Hemaquet was advanced
      and 4-mm deflectable tip catheter introduced into the pericardial sac to map the
      right and left ventricular epicardium. Transthoracic echocardiographic monitoring
      was performed on the day of the procedure and on the day of hospital discharge.
      The pericardial space was reached in all patients with no complications.
      Electrophysiologic data suggesting the existence of an epicardial circuit was
      found in one patient. No complications occurred during the hospitalization
      period. CONCLUSION: Epicardial mapping can be safely performed through a
      pericardial puncture in the electrophysiology laboratory.

PMID- 8743759
TI  - Pericardial space exploration for ventricular tachycardia mapping: should the
      countdown begin?

PMID- 8743760
TI  - Late diagnosis of pericardial constriction associated with defibrillator patches
      and deformation of the left ventricle.
AB  - We report a case of pericardial constriction associated with defibrillator
      patches developing 4.5 years after implantation. This constriction was related to
      the presence of a large pericardial mass that had developed above the
      defibrillator patch. This mass, which had a calcified superior border, suggested
      former hematoma associated with pericardial fibrosis. It induced significant
      compression of the right ventricle and a dumb-bell deformity of the left
      ventricle. The hemodynamic picture was of elastic-form constrictive pericarditis.
      Because of previous cerebral stroke during cardiac surgery, the patient was
      discharged on pharmacologic treatment after improvement of his functional status.
      Since removal of epicardial patches is an effective treatment of constriction,
      constrictive pericarditis should be systematically considered in patients with
      epicardial patch electrodes and impairment of functional status.

PMID- 8743761
TI  - Sensing and tachyarrhythmia detection problems in implantable cardioverter
      defibrillators.
AB  - Sensing of cardiac activity and detection of tachyarrhythmias in implantable
      cardioverter defibrillators (ICDs) are complex functions and errors occur.
      Sources of sensing-detection errors include the variable nature of intracardiac
      electrograms, the occasional inability of automatically adjusting signal
      amplifiers to cope with this variability, problems with sensing leads,
      inappropriate programming, and limitations of tachyarrhythmia detection
      algorithms, which are optimized to avoid underdetection of ventricular
      tachyarrhythmias. Current ICDs vary considerably in details of sensing and
      detection function, programmability, and diagnostic data, so that a through
      knowledge of each device is necessary to diagnose and correct these problems.
      Stored intracardiac electrograms and/or marker channels available in most of
      these devices have contributed much to our understanding of sensing-detection
      errors. Undersensing of individual signals, most frequently due to signal
      variability and/or inability of the amplifier to adjust adequately, can lead to
      delay or failure of tachyarrhythmia detection. Delay or failure of
      tachyarrhythmia detection can also occur if algorithms to enhance specificity,
      such as sudden onset or rate stability, are utilized. Oversensing of T waves or
      noise can lead to false detection; however, the most common cause of false
      detection is the inability of current detection algorithms to distinguish
      supraventricular from ventricular tachyarrhythmias. New algorithms that
      incorporate atrial sensing, electrogram morphology analysis, or hemodynamic
      monitoring may result in improved detection accuracy of ICDs in the future.

PMID- 8743762
TI  - Adenosine-sensitive ventricular tachycardia: a conceptual approach.
AB  - Idiopathic ventricular tachycardia (VT) is a term that refers to tachycardia that
      arises from ventricles devoid of apparent structural abnormalities. This form of
      VT is now recognized to be related to several distinct entities and includes a
      reentrant form typically located in the region of the left posterior fascicle, an
      automatic form that may originate from either ventricle, and a form that
      originates from the right ventricular outflow tract. This last type can account
      for up to 80% of cases of idiopathic VT and with few exceptions can be further
      subdivided into repetitive monomorphic VT and paroxysmal stress-induced VT.
      Evidence has accumulated suggesting that both forms of VT are related to cAMP
      mediated triggered activity. The experimental underpinnings of this conclusion as
      well as the clinical characteristics of this form of idiopathic VT are elucidated
      in this review.

PMID- 8743763
TI  - Transvenous defibrillation lead systems.
AB  - The use of the implantable cardioverter defibrillator has grown dramatically over
      the past 10 years. One of the major advances in defibrillation technology is the
      development of transvenous lead systems. Compared with traditional epicardial
      lead systems, transvenous defibrillation leads reduce perioperative mortality,
      hospitalization, and costs. Transvenous lead systems provide reliable sensing of
      ventricular tachyarrhythmias, although redetection of ventricular fibrillation
      can be prolonged, especially with integrated lead systems. Both ramp and burst
      adaptive pacing are equally effective for the termination of ventricular
      tachycardia and are successful in up to 90% of spontaneous events. Defibrillation
      thresholds are higher with transvenous leads than with epicardial patches. These
      thresholds are reduced with the use of multiple transvenous leads, subcutaneous
      patches, or with reversing shock polarity. However, the development of biphasic
      waveforms has made the largest impact on the efficacy of these lead systems,
      allowing dual coil transvenous systems to be effective in about 90% of patients.
      Defibrillation efficacy is further enhanced and implantation simplified by the
      incorporation of an active pulse generator located in the left pectoral region.
      Active pectoral pulse generators with biphasic waveforms will be the primary lead
      system for new implants.

PMID- 8743764
TI  - An electrocardiogram that demonstrates grouped beating: what is the rhythm?

PMID- 8743765
TI  - Intermediate length neuropsychological screening of impairment among psychoactive
      substance-abusing patients: a comparison of two batteries.
AB  - Two intermediate-length neuropsychological test batteries-the Brain Age Quotient
      T Scored (BAQ-T) and the Neuropsychological Screening Battery (NSB)-were used to
      evaluate the cognitive functioning of substance-abusing patients. Patients
      entering residential treatment for substance abuse (n = 30) performed
      significantly worse on both batteries compared to demographically similar
      participants from a nonclinical control group (n = 30). Both batteries
      categorized over one third of the substance-abusing patients as cognitively
      impaired; the chance-corrected agreement (kappa) of the BAQ-T and NSB in
      classifying participants as either cognitively impaired or intact was
      satisfactory. The comparative merits and limitations of each battery are
      discussed.

PMID- 8743766
TI  - The consumption of tobacco, alcohol, and coffee in Caucasian male twins: a
      multivariate genetic analysis.
AB  - Despite the fact that epidemiologic studies demonstrate a consistent covariation
      between the use of tobacco, alcohol, and coffee, most previous behavioral genetic
      studies have determined the contribution of genetic and environmental influences
      as if the consumption of these substances occurred independently of each other.
      In this study, we used multivariate structural equation modeling to determine the
      genetic and environmental overlap in the observed correlations between tobacco
      smoking and alcohol and coffee drinking in 173 monozygotic and 183 dizygotic male
      twin pairs (M age = 59 years; range = 52-66 years) who participated in a follow
      up cardiovascular examination of the National Heart, Lung, and Blood Institute's
      Twin Study. Consistent with hypothesized psychoneurogenetic predispositions for
      the joint use of these substances, the most parsimonious model fitting these data
      identified a common genetic latent factor underlying the observed associations
      between smoking, alcohol, and coffee use in this cohort. This factor, herein
      called polysubstance use, underscores the role of genetic influence on the
      clustering of these behaviors in the same individual.

PMID- 8743767
TI  - Substance-dependent inpatients who accept smoking treatment.
AB  - Delineating the characteristics of substance-dependent inpatients who are
      interested in receiving smoking treatment is critical to developing effective
      recruitment strategies and interventions for this population. Thus, this study
      comprehensively assessed and compared substance-dependent inpatients who accepted
      (n = 75) versus refused (n = 25) a stop-smoking treatment. Univariate analyses
      found treatment acceptors were younger, more addicted to nicotine, had more
      smoking-related health problems, had more positive attitudes about quitting
      smoking, and had more positive attitudes about the relationship between smoking
      cessation and drug/alcohol sobriety (e.g., believed cessation would positively
      impact sobriety). Logistic regression revealed that believing inpatient treatment
      was the best time to quit smoking was the primary factor associated with
      accepting treatment. Aside from their attitudes about the relationship between
      smoking cessation and sobriety, substance abusers who accepted smoking treatment
      appeared similar (e.g., in demographics, smoking behaviors) to nonabusers
      described in previous studies.

PMID- 8743768
TI  - Modeling therapeutic response to 12-step treatment: optimal responders,
      nonresponders, and partial responders.
AB  - Findings from alcohol treatment studies have had limited impact on clinical
      practice, in part because they have failed to accurately model treatment factors.
      This study attempted to model initial response to 12-step substance abuse
      treatment using a treatment theory-guided evaluation paradigm. A theory-guided
      measure of 12-step behaviors was constructed. Participants (N = 103) from two
      traditional substance abuse treatment programs were assessed at intake,
      discharge, and 1 month after discharge from intensive treatment. Results
      indicated that the measure of 12-step behaviors had adequate psychometric
      properties, and a one-factor solution best fit the data. Participants
      demonstrated substantial variability in their initial response to treatment. A
      cluster analysis of 12-step behaviors yielded three distinct groups of
      responders: optimal responders, partial responders, and nonresponders.
      Descriptive features and differences in relapse rates for groups are reported.
      Implications for matching patients to 12-step treatment and for clarifying the
      specific effects of this widely used treatment model are discussed.

PMID- 8743769
TI  - Spouse enabling of alcohol abuse: conception, assessment, and modification.
AB  - This article presents a conception of spouse enabling of partner alcohol abuse, a
      review of its dysfunctions, and an approach to assessment and modification to
      reduce spouse enabling behavior. Based on experience with its use in unilateral
      family therapy with many spouses of treatment-refusing alcohol abusers,
      procedural guidelines, treatment methods, two case examples from a crossover
      experimental dyad, and clinical results for the two cases in the dyad are
      described. Also presented are practice issues, characteristics of spouse enabling
      as they relate to disenabling intervention, and areas of possible application of
      the disenabling program.

PMID- 8743770
TI  - Diagnostic and referral reliability in an alcoholism treatment network.
AB  - Diagnostic and referral reliability were studied throughout an integrated
      alcoholism referral and treatment network. Diagnosticians included volunteers
      from an inpatient alcohol program staff, an outpatient referral network, a
      hospital medical staff, and a hospital administrative staff. Participant category
      had no influence on diagnostic reliability and only minimal influence on referral
      reliability. Cases involving only physical addiction to alcohol, particularly
      withdrawal symptoms, were more reliably diagnosed and referred than were cases
      involving psychosocial problems alone. Diagnostic practices included
      consideration of multiple problem areas for each case. Results are related to
      prior research findings and current directions in the diagnosis and treatment of
      alcohol disorders.

PMID- 8743771
TI  - Measuring tobacco withdrawal: a review of self-report questionnaires.
AB  - Little information exists on the various measures used to assess tobacco
      withdrawal. This article reviews the literature on the assessment of tobacco
      withdrawal, specifically comparing three commonly used self-report questionnaires
      of tobacco withdrawal. Several topics are discussed including (a) the frequency
      and duration of withdrawal assessment, (b) the determination of reliability and
      validity of self-report measures, (c) a comparison of the existing self-report
      instruments in terms of psychometric properties and other criteria, and (d) the
      physiological and behavioral assessment of tobacco withdrawal. Six
      recommendations for further research are offered.

PMID- 8743772
TI  - Coerced treatment for substance abuse problems detected through workplace urine
      surveillance: is it effective?
AB  - With the advent of on-site urine testing and other initiatives designed to reduce
      substance abuse at the workplace, employees who are found to have used alcohol
      and/or drugs have been coerced into substance abuse treatments under threat of
      job loss. This widespread practice has produced three questions relative to these
      practices. First, do these employees have significant substance abuse problems or
      are they merely "recreational users" who have gotten caught? Second, will these
      employees participate in standard treatments or will they resist them? Finally,
      will standard substance abuse treatments provide any benefits to these coerced
      patients relative to other self-referred patients in treatment? We compared the
      pretreatment problems, during treatment performance and posttreatment outcomes of
      96 employed, insured participants who were coerced into treatment at four private
      treatment programs due to detection of drug use on the job, to the same measures
      collected on a comparison group of 161 patients from the same job sites who were
      self-referred admissions to the same four treatment programs. Results showed that
      the coerced group had significant substance abuse and other life problems at the
      start of treatment, but that these problems were generally less severe or chronic
      than those of the self-referred group. Coerced participants were significantly
      more likely to remain in treatment (either inpatient or outpatient) than the self
      referred participants. Posttreatment follow-up of coerced patients indicated
      marked improvements in alcohol and drug use, employment, medical, family, and
      psychiatric problems. These levels of improvement were comparable to those shown
      by the self-referred patients. We conclude that workplace urine surveillance was
      successful in detecting employees with significant substance abuse related
      problems, and that referral to standard treatment was associated with substantial
      improvements in those problems.

PMID- 8743773
TI  - Personality differences related to smoking and adult attention deficit
      hyperactivity disorder.
AB  - Tridimensional Personality Questionnaire (TPQ) scores are compared for three
      groups of adults: (a) current smokers with Attention Deficit Hyperactivity
      Disorder (ADHDSmk, n = 14); (b) current smokers without ADHD (NonADHDSmk, n =
      21); and (c) ADHD never smokers (ADHDNevSmk, n = 17). The ADHASmk participants
      started smoking at a significantly younger age than NonADHDSmk participants. On
      the TPQ Novelty Seeking (NS) scale, all groups scored more than a standard
      deviation above the norm, and ADHDSmk participants scored significantly higher
      than NonADHDSmk participants. The earlier onset of smoking in ADHD adults
      suggests that smoking prevention efforts may be particularly important for ADHD
      children. Previous studies have reported that both smokers and ADHD patients have
      elevated NS scores; this study suggests an additive effect for smokers with ADHD.
      This exaggerated tendency towards thrill seeking in ADHDSmk participants may
      complicate smoking-cessation treatment in this population, because the health
      consequences of smoking may be of less concern to ADHD smokers.

PMID- 8743774
TI  - Depression following smoking cessation in women.
AB  - The recurrence of depression following smoking cessation has been documented
      among smokers with a history of depression. This report examines the development
      of major depression following smoking cessation among three women without notable
      histories of depression. Shortly after smoking cessation, these women developed
      significant depressive symptoms requiring psychiatric intervention. These cases
      seem to support the hypothesis that some smokers may self-treat negative affect
      with nicotine and underscore the importance of monitoring depressive symptoms in
      patients undergoing smoking-cessation treatment.

PMID- 8743775
TI  - [The pathogenesis of sepsis and the possibilities for its treatment using nondrug
      methods].
AB  - The substantiation of views to the foci of the "cryptogenic" infection and its
      nature in sepsis is given. The state of the redox system, immunological status
      and functions of the liver and kidneys in patients with complicated sepsis are
      investigated. The data on the influence of nonmedicamental methods (hemodialysis,
      AUVIB, HBO, EHS) upon the parameters of the redox system, cellular and humoral
      immunity in acute sepsis patients are presented. A complex of nonmedicamental
      methods, most effective in correction of homeostasis disturbances in sepsis is
      suggested and tested. An analysis of efficiency of each of the nonmedicamental
      methods has shown that they statistically promote the decreasing of lethality
      indices and the duration of the hospital treatment.

PMID- 8743776
TI  - [The use of surgical and therapeutic bronchoscopy in thoracic surgery].
AB  - The results of treatment of 260 patients who were subjected to 485 endoscopic
      operations with laser and electrosurgical methods are described. Excellent and
      good results were obtained in 199 patients (76.6%). The results of treatment of
      43 patients by means of temporary endobronchial occlusion showing its efficacy in
      pulmonary bleedings as well as in complex treatment of pneumo- and
      pyopneumothorax are presented. The therapeutic effect of the low intensity
      endobronchial laser therapy on complex prophylaxis and treatment of obstructive
      bronchitis after surgical intervention on the lungs and pleura as well as in
      complicated traumatic injuries of the chest is noted.

PMID- 8743777
TI  - [The interpretation of the data from the ultrasonic examination of patients with
      acute and chronic suppurative lung and pleural diseases].
AB  - Observations were made in 104 patients with acute and chronic lung abscesses and
      pleural empyema. The endoscopic, bacteriological and ultrasonic methods were used
      to make full diagnosis and to begin treatment. This article describes the part of
      the work devoted to the ultrasonic diagnostics. Different forms of lung abscesses
      were revealed and explained. The method was used to differentiate the collection
      of pus in the lung and pleural cavity, to reveal the structure of pathologic
      processes and its development, to learn the character of changes in the lungs and
      pleural space. The method is rather simple and gives the doctor much information
      about the condition of the pathologic tissue.

PMID- 8743778
TI  - [Resection of the esophagus with single-stage intrathoracic
      esophagogastroplasty].
AB  - An experience with treatment of 152 patients with diseases of the esophagus who
      were subjected to resection of the esophagus with a one-step esophagoplasty is
      analyzed. A principally new approach is presented to the method of forming the
      gastric transplant, to choice of the level of the esophagus resection and to
      preoperative examination of the patients. Postoperative lethality was 9.9% with
      the complete absence of the esophageal anastomosis incompetence.

PMID- 8743779
TI  - [The surgical treatment of hiatal hernias combined with diseases of the abdominal
      cavity organs].
AB  - An experience with treatment of 210 patients with hiatal hernias is summarized,
      162 (77.1%) of them having a concomitant pathology of the abdominal cavity. Most
      frequently the hiatal hernias were associated with gastroduodenal ulcers (48.6%),
      chronic cholecystitis (18.1%), ventral hernias (5.7%). A new method of correction
      of hiatal hernias is described which prevents the development of complications
      resulting from an extreme narrowing of the hiatus. Good long-term results were
      obtained in 55.9% of the patients, satisfactory--in 34.3% unsatisfactory in 9.8%
      of the patients, results of the isolated correction of the hiatus being worse
      that those obtained after the combined operations. A conclusion is made that well
      grounded simultaneous operations for hiatal hernias are followed by perfect
      medico-social and economic effects.

PMID- 8743780
TI  - [A comparative evaluation of the immediate results of a Billroth-II gastric
      resection with different methods for forming the gastrojejunal anastomosis].
AB  - The clinico-statistical investigation performed has revealed that the compressive
      suture of the transverse termino-lateral gastrojejunal anastomosis in gastric
      Billroth-II resection formed with the help of a titanium nickelide device
      considerably lowers traumatism of the operation and bacterial contamination of
      the operation area, abdominal cavity and the abdominal wall wound which leads to
      pronounced (3-4 times) drop of the level of early postoperative complications and
      minimizes the postoperative lethality.

PMID- 8743781
TI  - [The choice of the method for surgical intervention in patients with a duodenal
      ulcer and a very high gastric acid production].
AB  - Specific features of the gastric juice production and results of vagotomy,
      resection of 2/3 of the stomach and vagotomy with antrumectomy were studied in
      217 "hypersecreters". Taking into account that patients with very high gastric
      acid production have the elevation of both the Ist and IInd phases of gastric
      secretion, vagotomy and resection of 2/3 of the stomach, do not always inhibit
      their acidity and this category of patients have recurrent ulcers too often after
      these operations. Vagotomy with antrumectomy is followed by most reliable
      inhibition of acidity and saves hypersecreters from ulcers. Results of this
      operation are recognized to be excellent and good in 89.1% of the patients.

PMID- 8743782
TI  - [The vagotomy results in relation to the predominance of neural reflex or
      hormonal mechanisms regulating acid production in patients with a chronic
      duodenal ulcer].
AB  - Results of prognostic tests of vagotomy were studied in 365 patients with chronic
      duodenal ulcers (CDU). It was established that the atropin test can not be taken
      as the main criterion of prognosis of vagotomy. However, according to its results
      the patients can be divided into 2 groups: atropin sensitive (69.3%) and atropin
      resistant (30.7%). According to the parameters of the atropin test and the night
      gastric secretion the patients were divided into 3 groups: favorable (45.7%),
      doubtful (31.0%) and unfavorable (23.3%) prognosis of effectiveness of vagotomy
      with draining operations of the stomach.

PMID- 8743783
TI  - [The diagnostic and treatment characteristics of focal liver lesions using
      computed tomography].
AB  - Under analysis is an experience with examining and treatment of 167 patients with
      focal lesions of the liver using computed tomography. Percutaneous transhepatic
      puncture and draining the hepatic abscesses and cysts under control of computed
      tomography is an independent method of treatment used in 53 patients. The
      technique of performing the puncture and drainage is described. Specific features
      of surgical treatment of focal lesions of the liver are described. Decompression
      of bile ducts in the postoperative period is shown to be necessary. A conclusion
      is made about high efficiency of computed tomography in diagnosis and treatment
      of focal lesions of the liver.

PMID- 8743784
TI  - [Repeat liver resection for metastases of colonic cancer].

PMID- 8743785
TI  - [The autotransplantation of splenic tissue after splenectomy].
AB  - The problem of spleen tissue preservation after splenectomy by means of its
      autotransplantation is discussed. The experimental data of the comparative
      assessment of spleen tissue regeneration in greater omentum, gastric wall, serous
      muscle-submucosal flap of gastric greater curvature on the vascular pedicle are
      presented. Efficiency of autotransplantation methods and stimulation of
      adaptation processes after splenectomy by means of spleen tissue
      autotransplantation are evident.

PMID- 8743786
TI  - [The role of adoptive immunotherapy in the combined treatment of neglected forms
      of colorectal cancer (a preliminary report)].
AB  - Results of treatment of 24 patients with neglected colorectal tumors in the
      period from 1988 till 1994 are presented. Six patients had stage C and 18
      patients had stage D after Dukes. Methods of combined action on the tumor
      including dissection of the tumor and its metastases, using immunoadoptive
      therapy as extracorporal connection with the donor porcine spleen, intravenous
      infusions of interleukin-2 and chemotherapy were employed. All the patients with
      stage C according to Dukes are alive: the average period of observations was 1143
      +/- 206 days with intervals within the limits of 4,5-1,5 years. Seven patients of
      18 with stage D after Dukes are alive with the average period of observations
      1331 +/- 216 days and an interval of observations within the limits from 6 to 2
      years. Dead patients with stage D after Dukes lived 525 +/-98 days on the
      average, i.e. about 1,4 year. The employed method of combined treatment of
      colorectal tumors improves survival, prolongs the lifetime of patients with
      neglected forms of the disease.

PMID- 8743787
TI  - [The antibacterial and immunocorrective action of ozone therapy in peritonitis].
AB  - Ozone therapy was used in 74 patients with diffuse forms of purulent peritonitis.
      It allowed to make postoperative lethality 1.7 times less and the amount of
      complications 1.8 times less as compared with a group of 62 patients where ozone
      was not used.

PMID- 8743788
TI  - [A method of using rod devices for transosseous fixation].

PMID- 8743789
TI  - [The comparative characteristics of the efficacy of medium- and low-frequency
      ultrasound in treating the suppurative wound].
AB  - The investigation has been conducted to study the influence of middling and low
      frequency ultrasound on the culture of standard microorganisms in vitro and in
      vivo and on the wound process in 26 patients. It has been shown that the middling
      ultrasound has a priority bactericidal effect upon the microorganisms and the
      wound infection. It also makes the process of depuration more active.

PMID- 8743790
TI  - [Wounds of the abdomen and pelvis with damage to the major vessels].
AB  - The results of treatment of 144 patients with major vessels injuries in abdomen
      and pelvis injuries are performed. They had injuries of 146 vessels and of 220
      abdominal organs. Mean blood loss was 2620 ml. 39 persons died (27.1%). The main
      lethality causes: haemorrhagic shock, late admission to the hospital, non
      adequate angiosurgical service. The most characteristic errors in polytrauma:
      nonremoved major vessels injuries in laparotomy, unsuccessful attempts to stop
      bleeding and nonprofessional placing of a vascular suture, wrong sequence of
      operative instruments, defects of surgical service organization.

PMID- 8743791
TI  - [High obstruction of the gastrointestinal tract due to an accessory pancreas in
      an 8-month-old child].

PMID- 8743792
TI  - [The sequelae of severe burn emaciation in a 12-year-old child].

PMID- 8743793
TI  - [The surgical treatment of congenital hip dislocation in young children].
AB  - New methods of operative treatment of congenital dislocations in children are
      proposed as well as the methods of restoration of motility in the hip joint. All
      these developed methods tested in 300 patients (380 joints) exclude recurrent
      deformities and delay the development of coxarthrosis.

PMID- 8743794
TI  - [Intraoperative complications during the correction of heart defects under
      different levels of hypothermia].
AB  - An analysis of complications of the operative period in 241 patients operated
      upon under conditions of mild (up to 28 degrees C--in 141 patients) and deep
      hypothermia (less than 28 degrees C--in 100 patients) has shown that among
      operative complications there was prevalence of rhythm disturbances. During
      operations under conditions of deeper hypothermia the fibrillation of heart
      ventricles was almost 3 times higher while cooling lower than 26-27 degrees C was
      followed by the appearance of ciliary arrhythmia almost in all the patients. The
      frequency of early postoperative cardiac insufficiency was mainly determined by
      the efficiency of correction of the disease and little depended on the cooling
      level.

PMID- 8743795
TI  - [Massive lymphorrhea as a severe complication of pancreatoduodenal resection].

PMID- 8743796
TI  - [A syringe attachment for pleural puncture].

PMID- 8743797
TI  - [A device for laparoscopic transhepatic microcholecystostomy].

PMID- 8743798
TI  - [A new method for plastic repair of the inguinal canal in treating inguinal
      hernias].
AB  - An analysis of the 20-years experience with treatment of inguinal hernias is
      presented. Patients with "light" forms of inguinal hernias and with a good
      condition of the posterior wall, inconsiderable widening of the deep opening of
      the inguinal canal can be successfully treated by Martynov's and Girard's
      methods. In complicated forms of the inguinal hernia it is necessary to
      strengthen the posterior wall of the inguinal canal, in cases with big recurrent
      and repeatedly recurring hernias it must be completely reconstructed, often with
      the help of alloplasty. A method of alloplasty of the inguinal canal is proposed
      for complicated forms of inguinal hernias. Operations were made on 62 patients,
      recurrent hernias were noted in 2 patients (3.4%). Another method of operations
      is proposed used in men of young and middle age excluding traumas of elements of
      the spermatic cord. Operations were performed on 111 patients, recurrences were
      noted in 2 of them (2%).

PMID- 8743799
TI  - [Gallbladder torsion].

PMID- 8743800
TI  - [Rare complications of a femoral hernia].

PMID- 8743801
TI  - [Amputations in patients with arterial obliterating diseases].

PMID- 8743802
TI  - [The diagnosis of arteriovenous malformations of the brain by transcranial
      dopplerography (the dopplerographic semeiotics of arteriovenous malformations)].
AB  - The work is devoted to investigation of possible use of transcranial
      dopplerography as a method of noninvasive diagnosing of arteriovenous
      malformations of the brain. An analysis of results of investigations in 89
      patients with suspected arteriovenous malformations was made. A close correlation
      is confirmed between the parameters of the blood flow and the volume, diameter
      and type of the structure of the supplying arteries. Transcranial dopplerography
      was shown to allow the detection of arteriovenous shunts in the brain vessels
      which is one of main symptoms of the arteriovenous malformations.

PMID- 8743803
TI  - [A clinical trial of using ligation of the bronchus at its base in lung
      resections].

PMID- 8743804
TI  - [Experimental and clinical validation of using enterosorption in mechanical
      jaundice].
AB  - Experiments in 119 rats with the model of mechanical jaundice have shown the
      efficiency of enterosorption with polyphepan. The development of the pathological
      process was found to improve, lethality of the experimental animals to decrease.
      Favourable changes of the laboratory indices characteristic of endotoxemia were
      noted. The mechanism of medical action of enterosorption is realized by means of
      intensification of transfer of masses of metabolites and toxins through the
      intestine wall and their excretion through the gastrointestinal tract. One of
      important mechanisms of the medical action of enterosorption is the stimulation
      of intestinal peristalsis which is confirmed by data of the dynamics of
      bioelectrical activity. Enterosorption performed in 60 patients with mechanical
      jaundice was followed by a more rapid improvement of the general state, decrease
      of the indices characteristic of endotoxicosis as compared with 60 patients of
      the control group. The frequency of postoperative complications and lethality
      were reliably lower.

PMID- 8743805
TI  - [The use of auricular puncture in the combined treatment of acute cholecystitis
      in elderly persons].

PMID- 8743806
TI  - [Laparoscopic extraperitoneal hernioplasty in the treatment of patients with an
      inguinal hernia].
AB  - The first experience with using laparoscopic extraperitoneal hernioplasty with
      implant Prolene" in 300 patients since November 1992 is analyzed. The analysis of
      the original method of laparoscopic extraperitoneal hernioplasty has shown its
      efficiency and safety for patients with inguinal hernias (recurrences were noted
      in 2,3%).

PMID- 8743808
TI  - [Plastic surgery in the ingrown nail].

PMID- 8743807
TI  - [The use of a stent-catheter in the surgical treatment of hydronephrosis].

PMID- 8743809
TI  - [The A. L. Polenov Russian Neurosurgical Research Institute].

PMID- 8743810
TI  - [The surgical procedure in injuries to the colon].

PMID- 8743811
TI  - [Gastroduodenal hemorrhages of peptic origin and the outlook for using
      somatostatin (Stilamin)].

PMID- 8743812
TI  - [Prof. E. V. Pavlov (on the 150th anniversary of his birth)].

PMID- 8743813
TI  - Diagnostic pitfalls in the cytological interpretation of breast cancer.

PMID- 8743814
TI  - Fine needle aspiration cytology in male breast carcinoma.
AB  - A veterans' hospital-based retrospective, clinicopathological study was
      undertaken to evaluate fine needle aspiration cytology (FNAC) in the diagnosis of
      male breast carcinoma. Two hundred and forty histologically proven cases of
      breast carcinoma spanning a period 17 yrs were identified and 13 of these were in
      males. Nine of these male patients had FNAC performed and were reported by the
      same cytopathologist (L.I.B.). In 8 of these cases FNAC was diagnostic of
      carcinoma. No material from FNA was obtained for diagnosis from one of these
      patients. We concluded that FNA is a useful technique in the diagnosis of male
      breast carcinoma.

PMID- 8743815
TI  - Plasma cells with iron inclusions in two non-alcoholic Chinese women.
AB  - Plasma cells with iron granules are rare, especially among non-alcoholic
      individuals. We report two teetotaller Chinese women with nasopharyngeal
      carcinoma and non-Hodgkin's lymphoma, whose bone marrow studies revealed plasma
      cells with inclusions morphologically compatible with iron granules. The iron
      nature of the granules was confirmed by elemental analysis. The clinical
      significance and the exact mechanism of formation of these iron inclusions in
      plasma cells remain unknown.

PMID- 8743816
TI  - Salivary gland anlage tumor. A case with widespread necrosis and large cyst
      formation.
AB  - We describe a case of the salivary gland anlage tumor (congenital pleomorphic
      adenoma). The tumor arose in the nasopharynx as a pedunculated mass.
      Microscopically most of the tumor contained large necrotic areas which revealed
      squamous cell metaplasia resulting in the formation of large cysts. This feature
      has never been described previously in this tumor and might lead to an erroneous
      diagnosis.

PMID- 8743817
TI  - Pseudoepitheliomatous hyperplasia in Mycobacterium ulcerans infection.
AB  - Pseudoepitheliomatous hyperplasia of the epidermis occurring with Mycobacterium
      ulcerans skin infection may result in localization of the infected area with
      discharge of necrotic material, followed by healing leaving a depressed scar. The
      process represents more than simple re-epithelization of an ulcerated skin
      surface; it is a mechanism which produces active extrusion of necrotic material
      containing viable mycobacteria and should be seen as part of a protective
      physiological response to the infection.

PMID- 8743818
TI  - Abnormalities in type IV collagen immunoreactivity in human laryngeal cancers.
AB  - Abnormal patterns of expression of the basement membrane type IV collagen are
      observed in many human cancers. This study examines the immunohistological
      expression of type IV collagen in the basement membrane in human laryngeal
      squamous cell carcinomas (SCC) (n = 24). Non-neoplastic vocal cord polyps (n = 4)
      were used as controls. The formalin-fixed, paraffin-embedded tissues were
      sectioned and pretreated with protease prior to immunostaining for type IV
      collagen. There was a statistically significant difference in type IV collagen
      expression between laryngeal SCC and vocal cord polyps (p = 0.0001; chi 2 test
      with continuity correction). In laryngeal SCC (n = 24; 100%), type IV collagen
      distribution was discontinuous and irregular or absent around individual or
      groups of neoplastic cells. In contrast, all of the cases of vocal cord polyps (n
      = 4; 100%) displayed a continuous pattern of subepithelial basement membrane type
      IV collagen. This study has shown that abnormal distribution of type IV collagen
      occurs in laryngeal squamous cell carcinomas but not in non-neoplastic vocal cord
      polyps. This may be related to either abnormal synthesis or to the breakdown of
      the collagen and it may be of use as a potential biological marker in the study
      of laryngeal carcinogenesis.

PMID- 8743819
TI  - Lack of p53 immunoreactivity in pancreatic endocrine tumors.
AB  - Abnormal expression of the p53 tumor suppressor gene has been implicated in many
      human epithelial tumors. However recent evidence has revealed the absence of p53
      gene abnormalities or overexpression in some human endocrine cancers. This study
      examines the immunohistological expression of the p53 gene product using the
      monoclonal antibody DO-7, an antibody directed against both wild and mutant forms
      of p53 protein, and a streptavidin-biotin-peroxidase method, in pancreatic
      endocrine tumors (n = 16). None of the cases of pancreatic endocrine tumors
      showed evidence of p53 immunostaining. This finding is in contrast to that in
      pancreatic adenocarcinomas in which increased p53 immunoreactivity has been
      previously observed. These observations suggest that the p53 gene may not be
      important in the development of endocrine tumors of the pancreas.

PMID- 8743820
TI  - Iron tablets cause histopathologically distinctive lesions in mucosal biopsies of
      the stomach and esophagus.
AB  - Iron tablets are widely used in the community. Severe, sometimes lethal, damage
      to the gastrointestinal tract following overdose is well known, but there is less
      appreciation of the damage that can be caused by therapeutic dosage. In this
      histological study of three esophageal lesions and six gastric lesions (including
      one autopsy case), heavy iron accumulation was demonstrated within ulcer
      granulation tissue, in connective tissue and blood vessels of the mucosal lamina
      propria, and within glandular and squamous epithelium. The appearance was
      distinctive and was similar to that seen following overdosage, although more
      localized. Five of the patients studied had evidence of delayed esophageal or
      gastric emptying which could have contributed to the damaging effect of the iron
      tablets. In most of the patients ulceration appeared to have preceded the
      commencement of iron therapy, so that the iron probably exacerbated rather than
      initiated ulceration and stricture formation. Histopathological reporting of iron
      induced changes in endoscopic biopsies will alert clinicians to a correctable
      pathological process.

PMID- 8743821
TI  - Test and teach. Number Eighty-one. Diagnosis: Pulmonary endodermal tumor.

PMID- 8743822
TI  - Localization of cytochromes P450 in human tissues: implications for chemical
      toxicity.
AB  - Cytochromes P450 comprise a remarkably diverse superfamily of heme-thiolate
      proteins critical in the metabolism of numerous endogenous ligands and
      xenobiotics. Among the myriad of P450 substrates are many compounds of
      toxicological and pharmacological significance. The precise complement of
      cytochrome P450 isoforms in any given tissue may therefore be an important
      determinant of susceptibility to chemical-mediated toxicity. We have used a
      histological approach to study the distribution of individual P450s in human and
      rabbit gastro-intestinal tissues. We have focused primarily on P450 enzymes of
      importance in the metabolism of carcinogens, namely CYP1A1, CYP1A2, CYP2E1,
      CYP3A4/3A5 and CYP4B1. Here we give an overview of the distribution of these
      enzymes in human and rabbit tissues and discuss the possible toxicological
      implications of the results. In addition we will discuss the value of archival
      human tissue specimens for histological analysis of P450 distribution.

PMID- 8743823
TI  - Angiotensin converting enzyme inhibition and protein restriction in progression
      of experimental chronic renal failure.
AB  - This study examined whether the effects of protein restriction and angiotensin
      converting enzyme (ACE) inhibition on the progression of renal failure are common
      or additive. Male Sprague Dawley rats (12 wks of age) underwent 5/6 nephrectomy
      and were randomized to 20% protein diet (PD) (n = 9), 20% PD+enalapril (5
      mg/kg/day) (n = 10), 20% PD+felodipine (30 mg/kg/day) (n = 9), 6% PD (n = 9), 6%
      PD+enalapril (n = 9) or 6% PD+felodipine (n = 10). Protein restriction, enalapril
      or felodipine treatment all retarded progression of renal failure and development
      of glomerular lesions. Protein restriction and enalapril appeared to have
      additive effects in preventing glomerular sclerosis.

PMID- 8743824
TI  - Forebrain hypoplasia following acute prenatal ethanol exposure: quantitative
      analysis of effects on specific forebrain nuclei.
AB  - The effects of acute prenatal exposure to ethanol on the volumes and neuronal
      populations of selected forebrain nuclei of postnatal animals have been examined
      in a mouse model. Pregnant mice were exposed to ethanol (25% ethanol, either two
      doses at 0.015 ml/g separated by 4 hrs, or a single dose at 0.03 ml/g) on the 8th
      gestational day and the cytoarchitecture of the basal forebrain, paleo- and
      neocortex examined quantitatively at P15. Significant reductions in the volume
      and total number of neurons of ventromedial and central forebrain structures,
      such as the olfactory bulb, septal nuclei, diagonal band nuclei and
      caudatoputamen, were observed in mice exposed to the divided ethanol dose, but
      not following the single dose. The neocortex and primary olfactory cortex were
      also reduced in volume in offspring exposed to the divided ethanol dose. However
      increased neuronal density in some neocortical regions of ethanol-exposed
      offspring suggests that the total number of neocortical neurons is not
      significantly affected by acute ethanol exposure. The findings indicate that
      pulse exposure to ethanol on a single day of early development causes deficits in
      neuronal populations of the ventromedial forebrain and caudatoputamen even in
      offspring without other major malformations. The results also indicate that
      caution should be exercised in interpreting the significance of nuclear volume
      reduction in human infants with fetal alcohol syndrome (FAS) in the absence of
      neuronal density estimates.

PMID- 8743825
TI  - An evaluation of the in vitro activity of piperacillin/tazobactam.
AB  - Tazobactam is a new, irreversible inhibitor of bacterial beta-lactamases of
      staphylococci, plasmid-mediated beta-lactamases of the TEM and SHV types found in
      Escherichia coli and Klebsiella species and beta-lactamases of anerobes such as
      Bacteroides species. Its combination with piperacillin, a broad spectrum ureido
      penicillin, would be expected to improve the activity of piperacillin against
      staphylococci, TEM and SHV beta-lactamase producing Gram negative bacteria and
      anerobes. Minimal inhibitory concentrations (MIC) of piperacillin/tazobactam were
      determined for 1952 individual patient isolates of Gram positive and negative
      bacteria causing significant infections and compared with MIC values for
      cefotaxime, ceftazidime, ciprofloxacin, imipenem, ticarcillin/clavulanic acid.
      MICs were determined by agar dilution (NCCLS 1990 and 1992).
      Piperacillin/tazobactam had excellent activity against methicillin susceptible
      staphylococci, Streptococcus pneumoniae, Haemophilus influenzae, enterococci and
      organisms of the Bacteroides fragilis group. It was also active against the
      majority of Enterobacteriaceae and Pseudomonas aeruginosa isolates tested. It was
      not active against extended spectrum beta-lactamase (ESBL) producing Klebsiella
      species and some high level TEM and SHV beta-lactamase producing E. coli and
      Klebsiella species. Activity against Gram negative organisms capable of producing
      chromosomally mediated beta-lactamases was good, since in most organisms tested,
      the enzymes were not induced in sufficient quantities to cause antibiotic
      resistance. However some Enterobacter species were derepressed hyperproducing
      mutants; these isolates showed resistance to piperacillin/tazobactam since
      tazobactam does not inhibit these Class I beta lactamases. Activity was superior
      to ticarcillin/clavulanic acid for Gram negative rods. Imipenem was the most
      active agent against ESBL producing Klebsiella species. Piperacillin/tazobactam
      has a suitable spectrum of activity in vitro to suggest its use in monotherapy of
      mixed anerobic infections, mixed respiratory infections such as aspiration
      pneumonia and, in combination with an aminoglycoside, it would provide Gram
      positive as well as Gram negative cover of febrile episodes in immunosuppressed
      patients.

PMID- 8743826
TI  - Pitfalls in the use of random amplified polymorphic DNA (RAPD) for fingerprinting
      of gram negative organisms.
AB  - Two arbitrary PCR primers for random amplified polymorphic DNA (RAPD) bacterial
      fingerprinting were used to test factors which may affect RAPD PCR results. These
      primers have been used in previously published RAPD fingerprinting studies. As
      expected, the MgCl2 concentration and template concentration in the reaction
      mixture may affect the RAPD banding patterns. The results obtained were not
      comparable between runs when using the Hybaid thermal cycler when all other
      conditions were kept constant. Addition of DMSO, gelatin and repeated
      subculturing did not appear to affect the banding patterns. A second set of
      primers directed against known repetitive sequences in Gram negative bacteria
      (REP1/REP2 and ERIC2) were examined to compare with RAPD as a means of
      fingerprinting organisms. The reproducibility was excellent. The results suggest
      RAPD primers can provide some useful comparative information on suspected related
      strains when tested on the same day and under the same conditions. PCR using
      REP1/REP2 and ERIC2 primers may provide a more reliable and reproducible
      alternative method for fingerprinting Gram negative bacteria.

PMID- 8743827
TI  - Comparison of two commercial enzyme immunoassays with cytotoxicity assay and
      culture for the diagnosis of Clostridium difficile related diarrhea.
AB  - 184 stool samples were analysed for the presence of Clostridium difficile and
      toxins using the Meridian Premier Toxin A and TechLab Tox-A EIA kits, selective
      culture and cytotoxin assay. Of the 184 samples 36 stools tested positive for
      cytotoxin. In comparison the sensitivity and specificity of the EIAs and culture
      were as follows: Meridian, 72 and 87, TechLab, 64 and 95, and selective culture,
      83 and 96%, respectively. The positive predictive values and negative predictive
      values for the various methods were: Meridian, 58 and 93, TechLab, 77 and 92, and
      selective culture, 83 and 96%, respectively. Discrepant results to those obtained
      by cytotoxicity assay were encountered with both EIA kits evaluated and less so
      by culture. In this study direct isolation of Clostridium difficile from stool
      samples most closely paralleled the findings of the "gold standard" cell line
      cytotoxicity assay. It appears that a single test for the determination of
      Clostridium difficile disease is adequate, although a second method improves the
      predictability of the diagnosis. Direct culture of feces provided a reliable
      secondary procedure to cytotoxicity assay. The EIAs were simple to use, labour
      efficient and provided a rapid result. However the lack of sensitivity and
      relative expense did not justify their routine use in our laboratory.

PMID- 8743828
TI  - Chromoblastomycosis: a retrospective study of six cases at the Royal Darwin
      Hospital from 1989 to 1994.
AB  - Chromoblastomycosis, a localized chronic cutaneous and subcutaneous infection of
      the skin caused by pigmented fungi, is most common in the world's tropical and
      subtropical zones. The condition rarely occurs in Australia. We present 6 cases
      of chromoblastomycosis seen at the Royal Darwin Hospital, Northern Territory,
      from 1989 to 1994 and affecting predominantly male Caucasians ranging from 38 to
      71 yrs of age. Clinically the lesions were verrucous or nodular. They mimicked
      basal or squamous cell carcinoma, nevi or solar keratoses. Histopathologic
      findings were nonspecific. The only pathognomonic finding was the presence of
      brown spores or sclerotic bodies within granulomata or within microabscesses in
      the skin.

PMID- 8743829
TI  - An immunohistochemical method for the diagnosis of melioidosis.
AB  - In order to assess the usefulness of immunohistochemistry in the diagnosis of
      melioidosis, an infection by Burkholderia pseudomallei, polyclonal antibodies
      were applied to tissues from known cases of melioidosis and to other infected
      tissues. Formalin-fixed, paraffin-embedded tissues were stained by a modified
      immunoperoxidase technique. In autopsy tissues with inflammatory lesions of
      melioidosis, the cytoplasm of phagocytes and intact bacilli, both intra- and
      extracellular, were stained very strongly positive. Relatively more focal
      positive staining was observed in some but not all surgical biopsies from proven
      cases of melioidosis. In granulomas staining was mainly found in the central
      necrotic areas, with little staining of peripheral phagocytes. All control
      materials stained negative. Immunohistochemistry appears to be a useful
      diagnostic tool in melioidosis.

PMID- 8743830
TI  - Bilateral primary seminal vesicle carcinoma.
AB  - We report a rare case of bilateral primary seminal vesicle carcinoma in a 73 yr
      old Australian man. To our knowledge this case report is the 48th histologically
      confirmed case of primary seminal vesicle neoplasia and only the fourth reported
      case of primary bilateral seminal vesicle carcinoma. Macroscopically the tumor
      was localized to both seminal vesicles and the adjacent right lobe of the
      prostate. Histologically the tumor and metastases displayed a PSA, PAP and CEA
      negative, well differentiated papillary adenocarcinoma resembling the pattern of
      normal seminal vesicle epithelium. No other primary carcinoma in the body was
      demonstrated. The patient survived for 3 yrs and 4 mths without recurrence of
      tumor. The pathological criteria for acceptance of primary seminal vesicle
      carcinoma, difficulties in clinical/radiological detection of seminal vesicle
      tumors and CA-125 immunoreactivity are discussed.

PMID- 8743831
TI  - Median raphe cyst of the perineum presenting as a perianal polyp.
AB  - Median raphe cysts are uncommon congenital lesions most often found on the penis
      or scrotum. This report describes an anterior perianal lesion in a 62 yr old male
      and draws attention to this rarely described location and the unusually late
      presentation.

PMID- 8743832
TI  - [Prostaglandin E2--an effective alternative for the induction of labor].
AB  - The authors aimed at studying the local application of PgE2 as a method of labor
      induction. 50 pregnant women divided into 3 groups were studied: I with Prostin
      E2 - vaginal tablets of 3 mg. Dinoprostone. II with Prepidil gel - 0.5 mg.
      Dinfprostone, applied intracervically and III with additional stimulation with
      Oxytocin - 5 E as an i.v. infusion. The criteria used were: parity, gestational
      age, Bishop score indications for induction. Success is considered as normal
      delivery by the 24th hour. Indications for PgE2 application are prematurity
      praeeclampsia, fetal malformations, fetal death, grave obstetrics history, RH
      incompatibility. It was discovered that with Prostin E2, the active phase of
      labor is reduced thus leading to reduction of labor. The frequency of operative
      deliveries also reduced and there were better fetal outcome. Two important
      advantages were discovered--simple application and physiologic advantages--the
      woman in labor is mobile and thus not traumatised. The authors stress that PgE2
      application can be considered an effective method for labor induction.

PMID- 8743833
TI  - [Pregnancy and labor in 335 cases of high multiparity].
AB  - It had been accomplished an investigation upon the pregnancy and the birth of 335
      women in labour with high (> or = 5) parity (grandmultimaras = GM), including 11
      736 labour, taking place in the Clinic of Obstetrics of Pleven Medical
      University. Controllable group had been formed out of a 655 women in labour with
      a parity from 1 to 4. It had been used a questionnaire method. Higher in the main
      group was the frequency of a hypertension, placental pathology (pl. praevia,
      abruptio et retention placentae) and that of a transverse and oblique
      presentation of the foetus. Lower in GM was the frequency of the neonates with a
      very low birth weight < 1500 g (VLBW), the frequency of induction and stimulation
      of the labour act, and of episiotomy and ruptures of the perineum. We come to the
      conclusion about the low level of obstetric risk with GM when there was an
      accessible and a competent obstetric assistance.

PMID- 8743834
TI  - [The location of the placenta in pregnant women with one or more past cesarean
      sections].
AB  - We examined 282 pregnant women who have had one or more previous cesarean
      sections. The localization of placenta was done with ultrasound after 32 weeks of
      gestation. The control group consists of 1560 pregnant women without previous
      operative births. Placenta praevia is found in 3.9% in patients with previous
      cesarean sections and in 0.45% in the control group. The bleeding in the group of
      placenta praevia after previous operative births is observed in 44.4% against
      28.5% when the placenta praevia is in intact uterus. A significant dependence was
      found between the number of sections and the risk of placenta praevia and
      bleedings in the following pregnancy. Placenta praevia shows preference to the
      anterior uterine wall in 67% in scared uterus and in 33% in intact uterus. A very
      poor is the combination of febrile postoperative period with endometritis and
      very short interval to the next pregnancy. These conclusions are important for
      the prognosis and management of such pregnancies.

PMID- 8743835
TI  - [Social psychological studies of pregnant adolescents].
AB  - Extramarital pregnancies among adolescent girl is not only an obstetrical, but
      also a socio-psychological problem. By use of special methods (questionnaires, a
      scala for gravity of psycho-social stress. Eysenck's [correction of Isenk's] test
      and self score diagnostic test), 63 adolescent pregnant girls were studied aged
      13-16, of which 33 delivered and 30 terminated their pregnancies at will. Almost
      half of the girls were gypsies with little or no education and relatively healthy
      live style. In 70% of the cases family climate was saturated with conflicts. 48%
      of the pregnant girls accepted their pregnancy calmly, in 79% of the cases it was
      decided, 87% of the girls expected to marry the father of their children, and in
      30% the children were left for adoption. 33% of the patient were victims of rape
      and had negative relationship towards their pregnancy. In 41% the pregnant women
      exhibited introversion and in 38%--extroversion and in those who delivered the
      ratio was almost the same In this same group moderate to intense stress was
      almost the rule, while among those who terminate their pregnancies light stress
      was observed. Neurotic tendencies among those who delivered was also observed,
      likely due to the reaction towards the process of difficult adaptation to the
      fact of the extramarital delivery. In the studied group we didn't observe extreme
      cases of social disadaptation reached crises of the pregnancy, abortion or
      delivery

PMID- 8743836
TI  - [The perinatal results in underage mothers].
AB  - The perinatal problems in 625 newborn babies from adolescent mothers (13-16) have
      been observed and compared with those of a control group of 350 children. The
      average age in the studied group is 15.7 years. The average birthweight in 2940
      g. 20% of whom were born before 37 weeks The perinatal death rate in adolescent
      mothers is 1.9 times higher than that of the control group and 3 times bigger
      than the general population. Stillbirth is 11.2%. The reasons for the perinatal
      deaths were interpreted through alternative analysis. The basic reason has been
      found to be prematurity. The perinatal death rate in associated primarily with
      prematurity and chronic fetal distress and in the control group we have to
      consider the malformations and ablatio placentae. The unfavorable perinatal
      outcome are more frequent in the group of the low social status mothers and those
      with inadequate antenatal cares.

PMID- 8743837
TI  - [Obstetrical observations of single-parent pregnancies (based on data from the
      Clinique Universitaire de Gynecologie, d'Obstetrique et de la Reproduction in the
      city of Besancon, France)].
AB  - This investigation includes 369 women-patients from the region served by the
      clinic during the period 1988-1992. Some particularities are observed in the
      course of the monoparental pregnancies, related with the social characteristics
      of the pregnant unmarried women. They are younger than the women, who get
      pregnant in biparental families. More than the half have no profession. They have
      no or only primary education in 39.5% of the cases. These women appear late and
      more rarely for medical examinations surveillance. Almost 30% of these
      pregnancies are lately declared or not registered at all. The premature
      deliveries occur three times more frequently than in the other female population.
      The delivery flows spontanously more seldom (69% against 76%), more often a
      section caesarean is applied (8.5% against 7.5%). Data concerning the pathology
      during the term of pregnancy and postdelivery complications, are presented. In
      this group of women the number of those who are breast-feeding their babies is
      smaller (55% against 68%). It is recommended to carry out a similar study in
      Bulgaria in order to plan better founded measures for education and social
      support of women.

PMID- 8743838
TI  - [Serum zinc and its relation to diet during late pregnancy].
AB  - The influence of dietary intake on serum zinc in 44 pregnant women in the third
      trimester of pregnancy and 10 healthy controls were studied. For assessment of
      the dietary intake 5-d record were used. Zinc in serum was analysed by flame AAS.
      Dietary zinc intake below the RDA was recorded in both groups studied (pregnant
      and nonpregnant women). Serum zinc in 42.8% of the pregnant women was below the
      cut off value. Only 1 of the nonpregnant women was with low serum zinc. For
      comparing serum zinc of both groups add ratio of 9.56 was calculated. Zinc in
      diet correlates significantly with the energy intake, protein and animal proteins
      in diet. Serum zinc correlates with animal protein intake and total energy of the
      diet. Pregnancy is a significant modulator of zinc status, but nutritional factor
      is a very important determinant for maintaining optimal nutritional zinc status.

PMID- 8743839
TI  - [Changes in the level of lipid peroxidation in healthy pregnant women].
AB  - A cross-sectional study on the level of lipid peroxidation and nutrient intake of
      44 healthy pregnant women (34-36 gestation week) at average age 24.9 +/- 4.5
      years and 15 controls (nonpregnant, nonlactating) at average age 31.8 +/- 7.6
      years, was carried out. The level of lipid peroxidation was measured by the
      concentration of TBA-reactive substance (TBARS) in plasma and red blood cells and
      the concentration of reduced glutathione in red blood cells. The nutrient intake
      was studied by 5-day diet record. The results obtained showed an activation of
      lipid peroxidation in pregnant women evidenced by a statistically significant
      increase of TBARS in red blood cells. Nutrient density of the protein of animal
      origin, vitamin C and zinc was significantly diminished in the diet of pregnant
      women but their average daily intake of protein and vitamin C was higher than the
      recommended dietary allowances. Obviously the activated lipid peroxidation during
      pregnancy could not be related to inadequate intake of nutrients with antioxidant
      activity but most probably is a result of hormonal changes.

PMID- 8743840
TI  - [Serum levels of prolactin, progesterone and estradiol in nursing mothers].
AB  - The serum concentrations of prolactin, progesteron and estradiol affecting twenty
      four parturients in the puerperium period are studied. The proportion of
      prolactin on one hand in accordance with progesteron on the other hand are
      examined. The required condition for lactogenesis is serum concentration of
      prolactin above 100 ng/ml and the low levels of progesteron and estradiol. The
      effect of primary breast feeding on the level of prolactin concerning ninety
      suckling mothers has been studied. The installment of a breast six hours after
      child-bearing stimulates the prolactin synthesis whereas the late breast feeding
      after seventy-two hours decreases the concentration of prolactin and suppresses
      lactation.

PMID- 8743841
TI  - [The impact of premature rupture of the amniotic sac on uterine involution in the
      early puerperium].
AB  - The object investigation is determination premature rupture velamentorum ovi
      relation with uterus involution in early puerperium (1st-5th day). The object of
      study are 86 young mothers 17-34 years old after normal delivery divided into
      four groups 1st group (control)-56 young mothers with rupture velamentorum ovi up
      to 6 hours before delivery; 2nd-15 young mothers with rupture velamentorum ovi
      from 6 to 12 hours before delivery 3rd-12 young mothers with premature rupture
      velamentorum ovi 12-24 hours before delivery and 4th group-3 young mothers with
      premature rupture velamentorum ovi over 72 hours before delivery. RESULTS: It was
      found significance steady uterus involution in 4th group (p < 0.001) and in the
      1st day in the 3rd group (p < 0.005) Tere is large deviations on individual value
      in all group. Authors discuss probable mechanism on uterus involution Conclusion:
      The premature rupture velamentorum ovi over 24 hours before delivery provoke
      steady uterus involution in early puerperium, but without pathological deviation
      most probably as a result young mothers exchange mechanisms.

PMID- 8743842
TI  - [Experience in treating episiotomies after labor with ice].
AB  - It is known from literature influence on cryotherapy on the tissue structures.
      It's application cause vessel constriction factor for decrease exudative
      inflammations and edema), save enzyme and immune activity at the cells levels and
      increases regenerative processes in tissues On the 324 young mothers we fix ice
      over episiotomies from 1st puerperal day for 3 days. As a control group were
      episiotomies on the 254 young mothers one cryoprophylaxis. Complications (oedema,
      inflammatio, or suppuratio) at the 1st group was 5.55% and in the 2nd (control)
      group was 9.45%. These results give us reason to suppose, that cryoprophylaxis
      have even non essential effect on the processes on recovery on episiotomies after
      delivery.

PMID- 8743843
TI  - [A retrospective comparison between clinical cases and graphs of biorhythms].
AB  - The present article develops the hypothesis of the biorhythms in a retrospective
      study of 50 normal parturitions, 13 premature births of dead fetuses, 9 premature
      rip off of the placenta, 4 caesarean sections with spinal anaesthesia and
      unmotivated high arterial pressure and 2 cases of clinical death, one of which
      treated successfully to life again. The results show high mathematical
      probability, i.e. 53% of all the incidents had happened exactly in the most
      critical days. The authors consider correctly that a number of preliminary planed
      surgical interventions could be in conformity not only with the determined by the
      biorhythms days but with the most convenient for the patient hour, too. And this
      is a routine already in a lot of western countries, and especially in the fields
      of oncological surgery.

PMID- 8743844
TI  - [Our experience with the enteral feeding of low-birth weight infants].
AB  - A retrospective study is carried out on preterm babies born under 2000 grams who
      were treated in the intensive care unit of State Institute Hospital--Maichin dom
      for the period of 1990-1992. The aim of the study is to establish the optimal
      regime of nutrition for low birth weight infants using the experience in the
      Intensive Care Unit. The conclusion is made that preterm newborn babies in
      already stabilized condition have higher gain of weight if they begin to be fed
      earlier 8 times a day instead of 12 times a day.

PMID- 8743845
TI  - [The sensitivity to antibacterial preparations of enterococcal strains isolated
      from gynecological patients, pregnant women, puerperae and newborn infants].
AB  - The sensitivity to a given number of antibiotics of 205 strains of enterococci,
      isolated for a period of one year was studied. The enterococci were isolated from
      materials, sent for microbiological examination in different clinical settings 55
      strains of enterococci from the lower genital tract were tested (vaginal and
      cervical secretions), 36 strains from the upper genital tract (lochia, peritoneal
      aspirates, IUD), 8 strains from wounds (perineal and abdominal), 37 strains from
      urine and 69 strains from the newborns. There was a high sensitivity towards
      carbenicillin--92.7% towards azlocillin 91.2% and towards ampicillin--83.9% The
      strains, isolated from gynecologic patients showed increased resistance towards
      aminoglucosides--49.5% towards gentamycin and 46.5% towards amicacin. The
      resistance towards gentamicin in the newborns was 68.1%. The strains from urine
      were resistant to cyprofloxacine in 29.7%. All the enterococci tested were
      practically resistant to cefamandole and oxacilline. The author suggests that for
      initial therapy in proven or suspected enterococcal infection carbenicilline,
      azlocillin and ampicillin. They are suitable both for gynecologic patients and
      newborns. The aminoglucosides have to be administrated after testing because of
      the significant resistance found for the different strains. The same is true for
      erythromycin and cyprofloxacine

PMID- 8743846
TI  - [Cervicographic screening of women in early pregnancy].
AB  - Ninety six patients in early pregnancy were subjected to cervicographical
      screening. The follow findings were obtained: 50 (52,1%) negative cervicograms,
      44 (45,8%)--suspicious and 2 (2,1%) with technical defects. The accuracy of the
      investigation was verified through colposcopy and target biopsy. A sensitivity of
      59,1%; specificity of 77,5%; positive predictive value of 44,8%; negative
      predictive value of 85,9% and effectiveness of 73,1% were established. The
      applicability, possibilities and limitations of the method are discussed. Adapted
      structured cervicography report form according Stafl's criteria is proposed for
      the practice.

PMID- 8743847
TI  - [The relationship between genital chlamydial infection and the presence of
      cervical intraepithelial neoplasia].
AB  - A study was carried out on 128 women with clinical signs of cervicitis. Direct
      immunofluorescence was used for the diagnosis of genital chlamydial infection. 46
      (of total 128) were positive for C. trachomatis. (35.9%). Abnormal colposcopic
      findings were found in 38 women cervical biopsies were taken in 52 women. 8 women
      were positive for C. trachomatis in the group with abnormal colposcopic findings.
      24 were positive for C trachomatis in the group, where cervical biopsies were
      taken. Comparing the results it was found that genital chlamydial infection did
      not influenced directly the development of cervical intraepithelial neoplasia.

PMID- 8743848
TI  - [Diagnostic methods in endometriosis].
AB  - The overall accuracy of preoperative diagnosis is approximately 20% with a range
      of 4-83%. We investigated 100 women at the age between 27-61 years, operated with
      histologically proven endometriosis and we made an attempt to analyse some of the
      diagnostic methods. Abrasio probatoria was made in 17 of the operated women prior
      to operation. The hystological result from the abrasive material was not
      indicative for the presence of endometriosis. Ultrasound examination was made on
      24 operated women with endometriosis, but no one diagnosed endometriosis despite
      the description by many authors of characteristic ultrasound picture of
      endometriosis. Hysterosalpingography was made in 3 women with the endometriosis
      but despite the specific x-ray picture for endometriosis they were not diagnosed
      correctly. These data support the opinion of some authors that these diagnostic
      methods are not specific for endometriosis.

PMID- 8743849
TI  - [The effect of the preliminary treatment of endometriosis on the results of
      fertilization in vitro (based on data from the Clinique Universitaire de
      Gynecologie, d'Obstetique et de la Reproduction in the city of Besancon,
      France)].
AB  - Thirty-nine women, aged 20 to 40 years, suffering from endometriosis, were
      treated in three different ways before fertilization in vitro (FIV). Excluded
      from the trial were all cases of Seventy five stimulated cycles were carried out
      altogether for the purposes of FIV. The results of the three methods of
      treatment, in terms of number of pregnancies, obtained after FIV, are compared.
      RESULTS: First method: surgical treatment. It was applied to 4 patients,
      suffering from severe endometriosis. The FIV (6 stimulations) give rise only to
      one pregnancy, interrupted through spontaneous abortion, during the second month.
      Second method: therapeutic treatment. Applied to 17 patients (mild-7, moderate-7,
      and severe cases-3). The FIV (32 stimulations) brought 4 pregnancies, run
      normally to the term, and 2 pregnancies, interrupted through spontaneous
      abortions. Third method: combined (therapeutic surgical) treatment, applied to 18
      patients (mild-3, moderate-9, and severe cases-6). In this group the FIV (37
      stimulations) give best results: 9 pregnancies terminated successfully. Three
      false pregnancies were found (biochemically). No abortion. The possibilities and
      the restrictions of each method of treatment are discussed. These results are
      considered as an indication that combined (therapeutic-surgical) treatment is the
      most appropriate with a view to a successful following FIV.

PMID- 8743850
TI  - [Intrauterine pessaries and acute genital inflammation in women].
AB  - The performed clinic-statistical investigation has covered generally 2182
      patients, 946 patients of common group make use of intrauterine contraceptive
      pessaries and 1236 patients have been included on the other occasion. Generally
      14 832 menstrual cycles were followed up. There were used multivariational method
      and analysis for investigation of three and more risk factors at once. The
      essential connection between the presence of intrauterine pessary and increased
      risk of sharply inflammation of the genital apparatus had been established. The
      uterus was the most often affected--endometritis in sharp and chronic from in
      31.39% of cases, and in 3 cases pelvioperitonitis was diagnosed. The appearance
      of genitals inflammation under the pessary presence is connected also with the
      age, parity, the application time and the pessary use.

PMID- 8743851
TI  - [The enzymatic diagnosis of endocervicitis caused by Chlamydia trachomatis].
AB  - The authors compare the reliability of an enzyme method for diagnostics of
      chlamydial endocervicitis versus Clearview chlamydia test. The results suggest
      that the enzyme test may be applied with sufficient diagnostic reliability.

PMID- 8743852
TI  - [Gynecological operations in high-risk patients (a preliminary report)].
AB  - The incidence of post-operative complication has been studied in women with
      concurrent nor-gynaecological and gynecological diseases, such as: vascular
      diseases (varices, phlebothromboses, thrombophlebitis), hypertension, changes in
      cardiac status (age-associated. Angina pectoris, cardiac decompensations). ECG
      changes,valvular defects, increased blood sugar, pulmonary diseases, etc. The
      study was held retrospectively over 326 female patients who had undergone
      operations for the period 1992-1993.

PMID- 8743853
TI  - [Current trends in the diagnosis and treatment of genital discharge].

PMID- 8743854
TI  - [The testicular feminization syndrome].

PMID- 8743855
TI  - [Female sexuality after menopause].

PMID- 8743856
TI  - [The Wunderlych syndrome].

PMID- 8743857
TI  - [Rupture of follicular and corpus luteum ovarian cysts--the cause of acute
      gynecological abdomen].
AB  - The symptomatology of the ruptured follicular and corpus luteum cysts varies from
      clinical occult status to haemorrhagic shock according to clinical studies for a
      ten years period. The syndrome frequency is higher in women over 30 years of age
      at rate 1:2 of the follicular to luteum cysts affecting mainly the right ovary.
      Twenty percent of the patients have been treated conservatively. Preoperative and
      intraoperative diagnosis coincides in 92% of the cases.

PMID- 8743858
TI  - [A rare case of bladder exstrophy in a newborn infant].

PMID- 8743859
TI  - [Difficulties in the obstetrical management of the delivery of twins].
AB  - Authors points at that very often it is not possible to follow the routine scheme
      of medical behaviour in twins delivery. Every such case must be resolved
      individually according to concrete circumstances.

PMID- 8743860
TI  - [Obstetrical management in primiparae at term delivery with cephalic
      presentation].

PMID- 8743861
TI  - [Systen--transdermal estradiol for substitution following surgical menopause].
AB  - The authors investigate the clinical effect of transdermal system delivering 17
      beta-estradiol for treatment of 23 patients after bilateral ovariectomy for
      benign genital tumors. During four to six months treatment Kuppermann index falls
      and karyopyknotic and maturation indices rise significantly. The side effects are
      extremely rare. The authors recommend the widely use of Systen for replacement
      therapy in surgically induced menopause.

PMID- 8743862
TI  - [The conservative treatment of condylomata acuminata with Solcoderm].
AB  - The conservative treatment of the condylomata acuminata by Solcoderm is local,
      painless and ambulatory. One application of Solcoderm by a capillary pipette
      covering the pathologic formations is enough--they become rapidly devitalized and
      disappear within 4 weeks. Secondary infections on the treated area are extremely
      rare.

PMID- 8743863
TI  - [Tocolytic substituent treatment with Magnerot in threatened abortions and
      premature labor from the 16th to the 36th gestational week].
AB  - The Mg's low level in the sera and the urine correlate with clinical symptoms of
      uterine contraction in pregnant women from the 16th-36th gestation week. The
      authors present their experience with the use of removal tocolytic curing with
      Magnerot tabl. in the cases of 60 pregnant women with uterine pain and
      contractions from 16th to 36th gestation week and Pelvic Score after Bishop under
      4. The effect of the curing is remarkable till from the beginning in the first 4
      7 days of it, which is demonstrated with disappearing of the objective and
      subjective contractions (overviewed in obstetric monitor) and there is
      normalising of the paraclinical levels of the Mg in the sera and the urine, with
      normal pregnancy and birth of a healthy and alive child.

PMID- 8743864
TI  - Education and the future of preventive medicine.

PMID- 8743865
TI  - Barriers to learning preventive medicine: student experiences in undergraduate
      medical education.

PMID- 8743866
TI  - The preventive medicine manager: a new role for preventive medicine specialists
      in managed care.

PMID- 8743867
TI  - Preventive medicine training and managed care: current status and models for the
      future.
AB  - The specialty of preventive medicine and managed care organizations share many
      common philosophies. Ties have been established between these two groups, but
      opportunities exist for strengthening and expanding relationships. I identified
      six preventive medicine residencies with strong rotations at managed care
      organizations and surveyed them for basic information regarding their
      affiliations. Six medical directors of managed care organizations who are board
      certified in preventive medicine were also contacted and surveyed. Successful
      relationships between preventive medicine residencies and managed care
      organizations include (1) commitment to training in a managed care environment by
      the preventive medicine residency, (2) large, well-established managed care
      organizations, and (3) commitment by the managed care organization to preventive
      medicine, evidenced by a department of preventive medicine or a preventive
      medicine physician on staff. Issues related to the involvement of managed care in
      preventive medicine training include the uncertain interest of managed care
      organizations in graduate medical education and the growing need for managed care
      organizations to attain accreditation status that includes standards for
      preventive services. Preventive medicine and managed care should increase their
      ties in the future. Medical Subject Headings (MeSH): preventive medicine, managed
      care, health maintenance organization, graduate medical education, training,
      accreditation.

PMID- 8743868
TI  - Training and education for public health: the role of the U.S. Public Health
      Service.
AB  - In 1993 Assistant Secretary for Health Philip R. Lee commissioned an evaluation
      of U.S. Public Health Service (USPHS) activities in training and education for
      public health (TEPH). Findings revealed significant shortages of professionals
      and academic faculty in the public health fields of epidemiology, biostatistics,
      environmental and occupational health, public health nutrition, public health
      nursing, and preventive medicine. An inventory of PHS activities showed that
      about $217 million was spent on 151 public health and prevention training
      programs serving over 141,000 persons in fiscal year 1993. The $217 million
      amounted to about 18% of the total reported PHS training expenditures of $1.2
      billion and about 1% of the total spending of $19.4 billion in fiscal year 1993.
      The National Institutes of Health (NIH) and Health Resources and Services
      Administration (HRSA) had the largest training expenditures of $655 and $445
      million respectively, but spent only about 7% and 17% on public health and
      prevention training. Other PHS agencies had larger proportional investments in
      prevention, but the amounts were smaller. Priority recommendations were provided
      to Dr. Lee in seven key areas: advanced technology, core public health functions,
      policy and financing, academic-practice links, educational research, research
      training, and coordination. Together, these could dramatically increase the PHS
      proportional investment in TEPH. The PHS has a rich variety of resources for
      TEPH, but a lack of prioritization, coordination, and planning is causing
      opportunities to be missed. Medical Subject Headings (MeSH): public health,
      training, education.

PMID- 8743869
TI  - Training physicians to care for the underserved: preventive medicine residency
      community health center linkages.
AB  - The population of uninsured and underinsured individuals in the United States
      continues to grow, compounding problems of adequate access to medical care. Some
      of the medical needs of this population are met by community health centers
      (CHCs). However, CHCs often have difficulty recruiting and retaining physicians,
      especially those with skills in community medicine. This article describes a
      general preventive medicine residency program that has been successful in
      preparing physicians for practice in these settings-what we call training in
      community-oriented preventive medicine (COPM). At the heart of COPM training are
      mutually beneficial relationships between CHCs and the residency program. This
      process has been greatly facilitated through the use of Health Resources and
      Services Administration (HRSA) federal training grant support to "match" funds
      provided by CHCs. As of July 1994, 11 residents have entered the COPM track, with
      eight graduates and three current residents. Thus far, all graduates have
      remained involved in community-based medical care and preventive medicine
      activities for medically underserved populations. This training arrangement can
      serve as a model for other preventive medicine residency programs and for CHCs
      interested in enhancing physician recruitment and retention. Medical Subject
      Headings (MeSH): community-oriented preventive medicine, medically uninsured,
      preventive medicine residency training, community health centers.

PMID- 8743870
TI  - Teaching preventive cardiology: the consultation clinic.
AB  - Atherosclerotic heart disease is the principal cause of death in the United
      States and other industrial societies. Three major risk factors for developing
      coronary artery disease (hypertension, hypercholesterolemia, and smoking) are
      frequently seen in family practice patients. It is therefore important for family
      physicians to be able to assess an individual patient's overall heart disease
      risk and provide advice and counseling to reduce that risk. This article
      describes a teaching-consultation clinic in which family practice residents learn
      to assess cardiac risk in patients and develop counseling skills to manage that
      risk. The role of the family physician in relation to the cardiologist is also
      discussed. Medical Subject Headings (MeSH): preventive medicine, cardiology,
      residency.

PMID- 8743871
TI  - Preventive medicine: notes toward an agenda for change.
AB  - Preventive medicine is an exciting specialty that is often blocked in its
      progress by internal conflicts and external obstacles. We can all change this
      state of affairs. I present and compare definitions of important terms to clarify
      the discussion. Structural problems of the specialty include, among others,
      fragmentary representation, unfocused academic departments, lack of control over
      professionalization, and specialty identification, particularly with respect to
      occupational medicine. A set of suggested solutions to these problems include
      these actions: (1) federate the leading organizations into a coalition for
      organizational strength, without sacrificing their individual identities; (2)
      define the core content of the specialty once and for all by the mechanism of
      consensus-driven competency-based learning objectives; (3) build stronger bridges
      to clinical specialties other than family medicine, particularly to internal
      medicine; (4) restructure academic departments to form a preventive medicine unit
      as such, encouraging health care research and community medicine to connect
      principally with family medicine departments; (5) rethink specialty
      certification, including a model defining a knowledge and skills set in defined
      modules, which would be combined in various ways to support flexible specialty
      certification; and (6) integrate occupational medicine with preventive medicine
      generally by exploring issues of common interest and building closer
      institutional ties when the opportunity arises. These and other ideas might be
      discussed by the leadership of the principal public health and prevention
      organizations at a "summit" meeting, but some group must take the initiative to
      champion the cause. Medical Subject Headings (MeSH): preventive medicine, future,
      definitions, specialty certification, community medicine, population medicine.

PMID- 8743872
TI  - A survey of residency management training: general preventive medicine graduates.
AB  - General preventive medicine residents at the University of Arizona are introduced
      to management skills and issues during graduate medical training to prepare them
      for future administrative positions. Our objectives were to learn whether
      administration training was effective and if acquired skills are useful in
      present job duties of graduates. We mailed a questionnaire to former general
      preventive medicine residents who had graduated between 1983 and 1992. Twenty-one
      (81.8%) of the 26 graduates returned a completed questionnaire rating the extent
      to which certain training activities improved administration skills and assessing
      the extent to which residency training overall prepare them for administrative
      work. Ratings reflected adequate preparation and usefulness of skills on the job.
      The survey indicates that administrative training should begin during residency
      years and that a variety of short-term and long-term activities, organized
      throughout both academic and practicum years can produce reasonable success in
      graduates. Medical Subject Headings (MeSH): preventive medicine, training.

PMID- 8743873
TI  - Hypertension prevalence, awareness, treatment, and control among African
      Americans in the 1990s: estimates from the Maywood Cardiovascular Survey.
AB  - During the last decade, the decline in cardiovascular disease mortality slowed
      among African Americans, compared to the general population. Hypertension control
      is likely to play an important role in determining these trends. The Maywood
      Cardiovascular Survey provides estimates of the prevalence, awareness, treatment,
      and control of hypertension among African Americans. Between 1991 and 1993, we
      conducted a cardiovascular disease survey among 1,524 African Americans living in
      the Chicago suburb of Maywood, Illinois. Estimates of the prevalence, awareness,
      treatment, and control of hypertension (defined as blood pressure [BP] > or =
      140/90 mm Hg or self-reported taking of antihypertensive medications) were
      calculated and compared to U.S. population estimates for African Americans from
      NHANES II and III. The prevalence of hypertension in our sample was 32.7% (30.3,
      35.1). After age-adjustment to the U.S. population, prevalence was 29.9% (27.9,
      31.9), which is nonsignificantly lower than that reported for African Americans
      in NHANES III (32.4% [30.2, 34.6]). Awareness, pharmacologic treatment, and
      control on pharmacologic treatment were 81%, 56%, and 55%, respectively. These
      estimates are, respectively, 15%, 27%, and 42% higher than NHANES II and 7%, 9%,
      and 11% higher than NHANES III. Nonpharmacologic treatment alone may have
      accounted for up to 34% of hypertension control overall. Among previously
      diagnosed hypertensive subjects, risk factors for being untreated were male
      gender (odds ratio [OR] = 5.3 [1.3, 21.3]) and age < 45 years (OR = 3.8 [1.1,
      12.8]), and for being uncontrolled was age > or = 65 years (OR = 1.9 [1.1, 3.0]).
      Rates of hypertension awareness, pharmacologic treatment, and control on
      pharmacologic treatment are higher in this sample of African Americans than among
      African Americans in NHANES II and are comparable to those in NHANES III. The
      impact of nonpharmacologic treatments on control needs further consideration.
      Medical Subject Headings (MeSH): hypertension, nonpharmacologic treatment,
      African-American males.

PMID- 8743874
TI  - A survey of recreational sun exposure of residents of San Diego, California.
AB  - The incidence of skin cancer in San Diego is one of the highest in the nation.
      Research has documented that excessive unprotected exposure to ultraviolet (UV)
      radiation over time significantly increases a person's risk for developing
      various types of skin cancer. Our study investigated the amount of sun exposure
      and the practice of sun protection among San Diegans and examined factors thought
      to be associated with these behaviors. In April 1994, a random sample of 864 San
      Diego residents was surveyed by telephone. Because most survey questions
      specifically asked about sun exposure and sun protection when tanning versus
      recreating, the analyses were presented separately for recreators (i.e., those
      who spent time in the sun during the hours of 8:00 am and 6:00 pm for recreation
      last summer; n = 786) and tanners (i.e., those who spent at least 10% of their
      time in the sun to get a tan last summer; n = 464), a subset of recreators. Study
      results indicated that on average, 27% of the tanners' time in the sun last
      summer was spent getting a tan, and tanners reported using sunscreen about 50% of
      the time on both their face and body. In terms of sun protection while
      recreating, survey respondents reported using sunscreen on their face
      approximately 40% of the time compared to approximately 30% of the time on their
      body. Correlates of sun exposure and sun protection for both tanners and
      recreators included demographic characteristics, susceptibility factors,
      attitudes, and knowledge. The findings from this study support the need for
      education on skin cancer prevention. The practical implications of these findings
      are discussed in terms of appropriate community skin cancer prevention
      interventions. Medical Subject Headings (MeSH): skin cancer, sunlight, behavior.

PMID- 8743875
TI  - Extent of undiagnosed HIV infection in hospitalized patients: assessment by
      linkage of seroprevalence and surveillance methods.
AB  - Routine screening of hospitalized patients for human immunodeficiency virus (HIV)
      infection has been suggested as a method to identify undiagnosed HIV infection.
      To evaluate HIV seroprevalence and rates and risk factors for undiagnosed HIV
      infection among inpatients at an urban hospital, we linked a blinded HIV
      seroprevalence survey with data from a health care systemwide HIV surveillance
      registry. Consecutive nonobstetric adult inpatients admitted over four months had
      remnant samples of serum and plasma obtained and demographic and clinical data
      abstracted from hospital registration and outpatient encounter billing files.
      After linkage with the HIV registry, patient data were assigned a study code,
      individual identifiers were removed, and specimens were tested for HIV-1
      antibody. Of 2,825 eligible patients, 155 (5.5%) were HIV-seropositive: 139 (90%)
      with known infection and 16 (10%) with previously undiagnosed infection. Of those
      with previously undiagnosed infection, eight (5%) were newly diagnosed during
      hospitalization and eight (5%) remained undetected following hospitalization. For
      HIV-seropositive patients, previously undiagnosed infection was significantly
      more common among those with no use of the health care system in the past year
      than those with recent outpatient or inpatient visits (41.7% versus 4.6%, odds
      ratio [OR] = 14.9, 95% confidence intervals [CI] = 4.7, 47.1). Despite a
      relatively high hospital HIV seroprevalence, the rate of undiagnosed infection
      was low, suggesting that the percentage of the HIV epidemic remaining
      "undetected" may be smaller in some settings than suggested by previous studies
      of hospitalized patients. Linkage of surveillance data to blinded seroprevalence
      studies can be of value in estimating this "undetected" percentage and in
      evaluating the potential yield of routine HIV testing programs. Medical Subject
      Headings (MeSH): HIV infection, risk factors, HIV seroprevalence, inpatients, HIV
      screening, population surveillance.

PMID- 8743876
TI  - The psychological impact of modeling in a cancer survivors' fashion show.
AB  - Our objective was to assess whether cancer survivors can serve as models to
      promote cancer prevention and screening without suffering psychological
      discomfort themselves. The disease coping literature suggests that if women knew
      more about what cancer treatment and life after surviving cancer were like, they
      would be more likely to accept cancer screening tests. Because cancer survivors
      are living examples showing that people can survive and thrive after cancer,
      survivors have the potential to promote cancer screening by teaching others in
      their community. However, if cancer survivors are to be asked to accept this
      task, it is essential to demonstrate that this activity does not cause
      psychological suffering for them. Cancer survivors were invited (n = 31) or
      volunteered (n = 22) to model in a cancer survivors' fashion show. All were asked
      to complete a brief biographical sketch before the event and a convenience
      subsample was interviewed by a trained ethnographer. A brief questionnaire was
      mailed to the models after the event. Individuals who did not return the mailed
      questionnaire were contacted by telephone. Forty-two of the models completed the
      mailed questionnaire and 10 were contacted by telephone. The models tended to
      report that the experience was very positive for themselves (mean = 9.0, standard
      deviation [SD] = 1.3 on a scale of 0 to 10 where 0 is extremely negative and 10
      is extremely positive) and for their family and friends who attended the fashion
      show (mean = 9.1, SD = 1.3 on the same scale). Under the proper conditions,
      modeling survivorship to others can be a rewarding experience for cancer
      survivors. While the models are easy to recruit, it remains to be demonstrated
      that cancer survivors are effective lay advocates for cancer prevention and
      screening. Medical Subject Headings (MeSH): mammography, recruitment, cancer
      survivors, psychological effects.

PMID- 8743877
TI  - HIV sexual risk reduction interventions for women: a review.
AB  - AIDS has emerged as a serious public health threat for women. Reducing the risk
      for HIV infection among sexually active women requires the adoption of preventive
      strategies that effectively inhibit viral transmission. However, there is a
      paucity of published literature describing interventions targeted toward women
      and even fewer published reports evaluating their effectiveness. We conducted a
      search of HIV prevention interventions for women using the MEDLINE, ERIC and
      PSYCHLIT on-line computer database for the years January 1984-May 1995 to assess
      the effectiveness of interventions in increasing condom use during sexual
      intercourse. Interventions efficacious at increasing condom use applied a social
      psychological model of behavior to guide the development and implementation of
      the intervention, used randomized controlled designs to evaluate program
      efficacy, emphasized gender-related influences, were peer-led, and used multiple
      intervention sessions. While these findings are promising, methodologic
      limitations preclude any definitive assessment of programmatic efficacy. One
      challenge for future studies is to corroborate and extend these findings using
      rigorous methodologic research designs to evaluate programmatic efficacy, in
      particular, longer follow-up to assess stability of treatment effects over time.
      Another challenge is to understand the implications of previous research for the
      development of more gender-relevant interventions. The urgency of the HIV
      epidemic demands that the development and evaluation of HIV-prevention
      interventions tailored toward women remain a public health priority. Medical
      Subject Headings (MeSH): women, HIV/AIDS, interventions, prevention.

PMID- 8743878
TI  - A nuclear traffic jam: unraveling multicomponent machines and compartments.

PMID- 8743879
TI  - Mechanisms of transcription complex assembly.
AB  - Gene-specific activators control the access of RNA polymerase II (pol II) to
      promoters in several ways: by chromatin rearrangement involving an ATP-dependent
      SWI-SNF complex; by the synergistic recruitment of transcription factor IID
      (TFIID); and by either the sequential recruitment of basal transcription factors
      and pol II or the recruitment of a preformed pol II holoenzyme which includes
      most of the basal factors. One of the most significant recent developments has
      been the demonstration that distinct subunits of TFIID (namely subunits of the
      TATA-binding protein associated factor) target different activators, basal
      factors, and core promoter elements.

PMID- 8743880
TI  - Cyclin-dependent kinase 7: at the cross-roads of transcription, DNA repair and
      cell cycle control?
AB  - Cyclin-dependent kinase (CDK) 7 was originally implicated in cell cycle control
      by virtue of its ability to phosphorylate and activate other CDKs. Subsequently,
      both CDK7 and its partner, cyclin H, were found to be associated with the general
      transcription factor TFIIH, suggesting additional roles for CDK7 in transcription
      and DNA repair. During the past year, a third subunit associated with CDK7 and
      cyclin H has been characterized, and the functional link between CDK7 and RNA
      polymerase II has been strengthened.

PMID- 8743881
TI  - Transcriptional control of the cell cycle.
AB  - Although a significant amount of evidence has demonstrated that there are
      intimate connections between transcriptional controls and cell cycle regulation,
      the precise mechanisms underlying these connections remain largely obscure. A
      number of recent advances have helped to define how critical cell cycle
      regulators, such as the retinoblastoma family of tumor suppressor proteins and
      the cyclin-dependent kinases, might function on a biochemical level and how such
      mechanisms of action have been conserved not only in the regulation of
      transcription by all three RNA polymerases but also across species lines. In
      addition, the use of in vivo techniques has begun to explain how the activity of
      the E2F transcription factor family is tied to the cell cycle dependent
      expression of target genes.

PMID- 8743882
TI  - The DNA-dependent protein kinase: a matter of life and (cell) death.
AB  - The catalytic subunit of the DNA-dependent protein kinase (DNA-PK) is a member of
      the phosphatidylinositol 3-kinase family. Recent genetic and biochemical studies
      indicate the involvement of DNA-PK in immunoglobulin/T-cell-receptor gene
      recombination, double-strand DNA break repair, the stress response and
      autoimmunity. A role in the suppression of apoptosis could link some of the
      enzyme's diverse functions.

PMID- 8743883
TI  - Biochemistry and regulation of pre-mRNA splicing.
AB  - During the past year, significant advances have been made in the field of pre
      mRNA splicing. It is now clear that members of the serine-arginine-rich protein
      family are key players in exon definition and function at multiple steps in the
      spliceosome cycle. Novel findings have been made concerning the role of exon
      sequences, which function as both constitutive and regulated enhancers of
      splicing, in trans-splicing and as targets for tissue-specific control of
      splicing patterns. By combining biochemical approaches in human and yeast
      extracts with genetic analysis, much has been learned about the RNA-RNA and RNA
      protein interactions that are necessary to assemble the various complexes that
      are found along the pathway to the catalytically active spliceosome.

PMID- 8743884
TI  - Control of gene expression by proteolysis.
AB  - The proteasome and the small protein ubiquitin are key elements in the
      intracellular pathway of general protein degradation. Recent evidence shows that
      the proteasome and other less well defined cytoplasmic proteases can participate
      in specific events which control inducible gene expression. A number of
      eukaryotic transcriptional regulators, including NF-kappa B/l kappa B, p53, c
      Jun, Notch, sterol regulated element binding proteins and MAT2 alpha, have
      recently been shown to be regulated by proteolytic events, a regulation which
      results in the activation or inactivation of gene expression.

PMID- 8743885
TI  - Imprinted genes and regulation of gene expression by epigenetic inheritance.
AB  - Six new imprinted genes have recently been identified by association with
      established imprinted regions, in systematic screens or by serendipity. This
      brings the total to seventeen imprinted genes, which display a wide variety of
      functions. Some imprinted genes have been shown to be both physically and
      mechanistically linked within domains that are under the control of an imprinting
      centre. Others may apparently undergo imprinting independently. Methylation is
      clearly required for maintenance of mono-allelic expression while chromatin
      structure and non-coding RNAs may also play a role.

PMID- 8743886
TI  - Influences of the cell cycle on silencing.
AB  - Silencing in Saccharomyces cerevisiae is a form of transcriptional repression
      that involves the assembly of a specialized and heritable structure of chromatin.
      The HML and HMR loci, which contain copies of the genes found at the yeast mating
      type locus, are silenced, as are telomeres. These examples share several features
      which are also found in position-effect variegation in flies and X-chromosome
      inactivation and genomic imprinting in mammals. Silenced chromatin is confined to
      a few special domains of the yeast genome, and active genes inserted into these
      domains become silenced. Molecular and genetic evidence has suggested that the
      establishment of silenced chromatin requires some S phase specific function.
      Recent experiments indicate that the assembly and maintenance of silenced
      chromatin can also be influenced at other phases of the cell cycle.

PMID- 8743887
TI  - Transcriptional repression in development.
AB  - It is becoming increasingly clear that transcriptional repression is at least as
      important as transcriptional activation for establishing cell-type specific
      patterns of gene expression during embryogenesis. Recent studies in Drosophila
      suggest that repressors fall into two categories, short-range and long-range
      repressors. The former permit enhancer autonomy in modular promoters, whereas the
      latter function in a dominant fashion to silence multiple enhancers.

PMID- 8743888
TI  - Organization of DNA into foci during replication.
AB  - In metazoan cells, DNA replication during the S phase of the cell cycle takes
      place at discrete locations within the nucleus. These sites, or foci, appear to
      participate in clustering many replicons together and synchronously regulating
      the activation of these replicon units. Consistent with this role. many
      replication proteins have been observed to attach to foci during the S phase of
      the cell cycle. Recently, cell-free replication extracts have been used both to
      characterize the events that are involved in either the formation of these sites
      or in the regulation of foci assembly, and to purify candidate proteins which may
      be integral core structural proteins responsible for forming foci. These advances
      provide a foundation for investigating foci structure and function at a
      biochemical level.

PMID- 8743889
TI  - Nucleosome assembly: the CAF and the HAT.
AB  - Recent data argue strongly that a protein complex termed chromatin assembly
      factor-1 (CAF-I) plays a major role in de novo nucleosome assembly during DNA
      replication. Human CAF-I deposits newly synthesized, acetylated histones onto
      replicated DNA in vitro and localizes to sites of DNA replication in S-phase
      cells. Specific lysines of the histones used for nucleosome assembly are
      acetylated; in the past year the first gene encoding a histone acetyltransferase
      was cloned. However, mechanistic links between histone acetylation and nucleosome
      assembly have not been established in vivo or in vitro.

PMID- 8743890
TI  - Structure and function of telomerase.
AB  - The study of eukaryotic telomeres at the molecular level began with the discovery
      of short, tandem repeats at Tetrahymena chromosome ends. In the following two
      decades, major insights about telomere structure and function have come from
      investigations of telomerase, the DNA polymerase that synthesizes these repeats.
      In the past year, three areas of telomerase research have been particularly
      intense: assays of telomerase activity, isolation of telomerase components, and
      studies of the regulation of telomerase and telomere length in vivo.

PMID- 8743891
TI  - Kinetochore function: molecular motors, switches and gates.
AB  - Kinetochores are essential for accurate chromosome segregation. Recent studies
      reveal that vertebrate kinetochores are sophisticated propulsion systems composed
      of not only force generators but also "navigation' and "fail-safe' mechanisms.
      Advances toward the understanding of the biochemical composition and activities
      of the components of the kinetochore have come from the molecular
      characterization of key proteins of the kinetochore complex.

PMID- 8743892
TI  - Synaptonemal complexes: structure and function.
AB  - Synaptonemal complexes (SCs) are zipper-like structures which are assembled
      between homologous chromosomes during the prophase of the first meiotic division.
      Their assembly and disassembly correlate with the successive chromatin
      rearrangements of meiotic prophase, namely the condensation, pairing,
      recombination and disjunction of homologous chromosomes. It was originally
      thought that SCs created the preconditions for the homologous crossing over of
      chromosomes by bringing corresponding parts of homologous chromosomes in close
      apposition. However, this view has been gradually undermined during recent years,
      and ideas about the roles of SCs have radically changed. SCs are now considered
      to be structures that both control the number and distribution of reciprocal
      exchanges between homologous chromosomes (cross-overs) and convert cross-overs
      into functional chiasmata. How SCs fulfil these roles remains to be elucidated.

PMID- 8743893
TI  - Toward the molecular dissection of protein import into nuclei.
AB  - Transport of proteins, RNAs and ribonucleoprotein particles into and out of the
      nucleus is essential for many cellular functions to proceed. Recent progress in
      this area of research has led to the identification of a number of signals and
      cytosolic factors that mediate the nuclear import of proteins through the nuclear
      pore complexes. However, as the sites on the nuclear pore complex at which these
      signals and factors exert their function are still largely unidentified, the
      molecular mechanisms underlying this nuclear import pathway remain to be
      elucidated.

PMID- 8743894
TI  - Nucleus and gene expression.

PMID- 8743895
TI  - Genetics and molecular biology.

PMID- 8743896
TI  - Apolipoprotein E as a risk factor for coronary heart disease: a genetic and
      molecular biology approach.
AB  - For a long time it has been suggested that apolipoprotein E4 is a major risk
      factor for coronary heart disease although indisputable proof has been lacking.
      However, context-dependent influences of apolipoprotein E polymorphism on the
      risk for coronary heart disease have been reported; that is, depending on ethnic
      origin, gender and lifestyle, apolipoprotein E4 confers a major risk factor for
      coronary heart disease.

PMID- 8743897
TI  - Regulatory mutations in human lipoprotein disorders and atherosclerosis.
AB  - Most known mutations underlying human lipoprotein abnormalities affect the
      protein coding sequence of the gene involved. Mutations in the regulatory regions
      promoters, enhancers, binding sites for transcription factors and other elements
      may markedly alter the transcription efficiency of lipid-regulatory genes, and
      may thus cause an inherited defect of lipoprotein metabolism. Reported examples
      include mutations of the promoters of the human LDL and lipoprotein lipase genes.
      Common variation of the DNA sequence in the promoter region, such as that
      occurring in the human apolipoprotein A-I and plasminogen activator inhibitor(-1)
      genes, may account for subtle differences in serum lipid levels and risk of
      atherosclerotic vascular disease in the general population.

PMID- 8743898
TI  - Paraoxonase: biochemistry, genetics and relationship to plasma lipoproteins.
AB  - Human serum paraoxonase is located on an HDL. It has the capacity to retard the
      accumulation of lipid peroxides in LDL under oxidizing conditions in vitro.
      Paraoxonase has a genetic polymorphism that results in a single amino acid
      substitution. Evidence indicates that both the serum concentration of paraoxonase
      and an individual's genotype are related to plasma lipid and lipoprotein
      concentrations, and possibly also to coronary heart disease, implicating
      paraoxonase in the development of atherosclerosis.

PMID- 8743899
TI  - Genetics and molecular biology of hepatic lipase.
AB  - Hepatic lipase is emerging as a major factor in the control of HDL metabolism.
      Hepatic lipase plays a central role in the hydrolysis of HDL2 triglycerides and
      phospholipids and in the concomitant apolipoprotein A-I efflux from this density
      class. New data suggest that allelic variation at the hepatic lipase gene locus
      accounts for 25% of the total variability in HDL cholesterol. Recent information
      suggests that this lipase may enhance the uptake of lipoproteins by cell surface
      receptors.

PMID- 8743900
TI  - Molecular mechanisms of reverse cholesterol transport.
AB  - The initial step of reverse cholesterol transport, the efflux of cell cholesterol
      into the extracellular fluid, has received much attention over the past year.
      Some studies have provided insights into the mechanism of cholesterol efflux and
      others have focused on the identity of the extracellular acceptors of cell
      cholesterol. Attention has also been directed towards the influence of HDL
      composition on the ability of these lipoproteins to accept cell cholesterol.
      There have been several studies addressing the importance of pre-beta-migrating
      HDL and of lipid-free apolipoproteins as acceptors of cell cholesterol. On the
      basis of these and earlier reports, a hypothetical cycle is proposed in which
      lipid-free apolipoprotein A-I dissociates from plasma HDL and transfers into the
      interstitial space where it acquires phospholipids and cholesterol from cells and
      becomes a discoidal HDL. Discoidal HDL transfer via lymphatics to the plasma
      where they are converted into mature HDL, thus completing the cycle.

PMID- 8743901
TI  - Molecular biology of phospholipid transfer protein.
AB  - Lipid transfer proteins play an essential role in the intravascular dynamics of
      lipids among lipoproteins and between lipoproteins and cell membranes.
      Phospholipid transfer protein has been known for over a decade but, unlike
      cholesteryl ester transfer protein, has been investigated relatively little with
      regard to its physiological importance. The recent determination of the
      phospholipid transfer protein complementary DNA sequence as well as the further
      characterization of its gene structure will direct future studies toward the
      understanding of its structure-function correlations, physiological regulation,
      and clinical assessment at the molecular level. As a member of the lipid-transfer
      lipopolysaccharide-binding protein gene family, phospholipid transfer protein
      will attract investigators to studying its possible involvement in
      lipopolysaccharide or endotoxin interactions in addition to its phospholipid
      transfer activity.

PMID- 8743902
TI  - Cellular and molecular biology of vascular remodeling.
AB  - The vascular system undergoes remodeling throughout life, first as primitive
      vessels form and reorganize, then as the circulation accommodates changing tissue
      perfusion requirements. Recent investigations that have targeted receptor
      tyrosine kinases have elucidated fundamental mechanisms that are involved in
      early formation and restructuring of blood vessels. Distinct receptors for
      vascular endothelial growth factor, and other receptor tyrosine kinases, appear
      to regulate very different aspects of early vessel formation including
      endothelial cell differentiation, tube formation and differentiation of blood
      vessels into microvasculature versus large vessels. In later development and in
      the adult circulation, remodeling adapts arteries to chronic changes in
      hemodynamic function. Furthermore, novel findings of how vascular cells transduce
      the hemodynamic forces to which they respond have been reported. Force-sensitive
      gene transcription occurs by previously characterized transcription factors that
      bind to both established and novel responsive elements in promoter regions of
      relevant genes. There now is evidence that more than one of these factors can
      regulate gene expression in response to a single physical force (shear stress).
      Recent studies have emphasized the role of matrix degradation and cell death, in
      addition to matrix synthesis and cell proliferation, in arterial remodeling. The
      importance of cell death and matrix degradation has also been emphasized in the
      pathogenesis of vascular pathologies. As a result of these and other findings,
      the role tissue remodeling is being examined closely as a primary factor in the
      pathogenesis of atherosclerosis, hypertension and restenosis after angioplasty.

PMID- 8743903
TI  - The atherosclerosis-calcification link?
AB  - Although previously believed to be a passive, degenerative process, there is
      increasing evidence that arterial calcification is actually an active, regulated
      process. In this review we address potential mechanisms of arterial calcification
      and, in particular, ways in which it is similar to bone formation. We also
      advance the hypothesis that particular factors present in atherosclerosis, such
      as lipids, may explain the co-localization of calcification and atherosclerosis
      in vivo.

PMID- 8743905
TI  - Genetics and molecular biology.

PMID- 8743904
TI  - Adenovirus-mediated gene transfer: strategies and applications in lipoprotein
      research.
AB  - Adenovirus-mediated gene transfer into mammalian liver is a highly efficient
      process that can result in transduction frequencies approaching 100%. Coupled
      with efficient expression levels from these vectors, the transfer of genes
      encoding a variety of enzymes, ligands and receptors has resulted in
      physiologically significant effects on lipoprotein metabolism. Adenovirus vectors
      have not only proved useful in the study of lipoprotein metabolism, they may also
      ultimately be used for hepatic gene therapy of inherited monogenic and polygenic
      disorders. The main hurdle to overcome before this technology can be
      therapeutically applied is the relatively short duration of expression in
      immunocompetent hosts. Apparently, cytolytic T-lymphocyte-mediated rejection of
      the transduced hepatocytes is caused by low-level expression of adenovirus genes.
      Several strategies have been recently employed in an attempt to circumvent this
      immune response and prolong transgene expression.

PMID- 8743906
TI  - Nutrition and therapeutics.

PMID- 8743907
TI  - Genetics and molecular biology.

PMID- 8743908
TI  - Lipid metabolism.

PMID- 8743909
TI  - Hyperlipidaemia and cardiovascular disease.

PMID- 8743910
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 8743911
TI  - Therapy and clinical trials.

PMID- 8743912
TI  - Metabolic bone disease of liver cirrhosis: is it parallel to the clinical
      severity of cirrhosis?
AB  - Metabolic bone disease has long been recognized in chronic liver disease,
      especially cholestatic or alcoholic liver diseases. The aim of the present study
      was to investigate the prevalence and severity of osteodystrophy in cirrhotic men
      and the correlation of its incidence with the clinical severity of cirrhosis in
      an endemic area of post-necrotic hepatitis. We measured serum levels of
      osteocalcin, 25-hydroxyvitamin D, parathyroid hormone mid-molecule, calcium and
      testosterone in 74 cirrhotic men (Child-Pugh's classification grade A n = 30, B n
      = 21 and C n = 23) and 16 healthy controls. Standard X-rays and bone mineral
      densities of lumbar spine were performed in 30 patients with post-necrotic
      cirrhosis and 10 healthy controls. Serum levels of osteocalcin, parathyroid
      hormone and testosterone were significantly lower in patients with cirrhosis than
      in controls. Changes paralleling an increased severity of cirrhosis were found in
      serum levels of 25-hydroxyvitamin D and testosterone, but not in the serum levels
      of osteocalcin and parathyroid hormone. The lumbar bone mineral density was
      significantly lower in patients with post-necrotic cirrhosis than in controls
      (0.97 +/- 0.13) vs 1.07 +/- 0.12 g/cm2, P < 0.05) and was correlated with serum
      25-hydroxyvitamin D levels (r = 0.467; P < 0.005). There was no correlation
      between the bone mineral density and serum osteocalcin or the clinical severity
      of cirrhosis. The prevalence of spinal osteoporosis, as defined by a lumbar bone
      mineral density greater than two standard deviations below the mean value of the
      controls, was 20% in cirrhotic patients compared with 10% in controls. Two (6.7%)
      patients (both grade C) had spinal compression fractures compared with none in
      the control group. In conclusion, serum osteocalcin and lumbar bone mineral
      density were significantly lower in cirrhotic men than in controls. However, they
      were not correlated with each other or the clinical severity of cirrhosis.

PMID- 8743913
TI  - Hyperglucagonaemia in cirrhotic patients and its relationship to the severity of
      cirrhosis and haemodynamic values.
AB  - Plasma glucagon concentrations were measured in 160 cirrhotic patients (Pugh's
      grade A in 52 patients, Pugh's grade B in 64 patients and Pugh's grade C in 44
      patients). These values were compared with plasma glucagon concentrations in 57
      age and sex-matched healthy subjects. Systemic and portal haemodynamic
      measurements, effective renal plasma flow and creatinine clearance were recorded
      for each patient. Plasma glucagon levels were significantly increased in
      cirrhotic patients compared with healthy subjects. In addition, plasma glucagon
      levels were higher in cirrhotic patients with ascites than in those without
      ascites and were increased in relation to the severity of cirrhosis as assessed
      by Pugh's score. Multiple linear regression found that only Child-Pugh's score
      was estimated to be an independent predictor of hyperglucagonaemia in cirrhotic
      patients. However, in patients with different degrees of oesophageal varices and
      in patients without oesophageal varices, plasma glucagon concentrations were no
      different among the different groups of patients, but were still higher than
      plasma glucagon concentrations in healthy subjects. In contrast, plasma glucagon
      levels were negatively correlated with mean arterial pressure and systemic
      vascular resistance. The results of the present study suggest that impairment of
      liver function plays, in part, a role in increased plasma glucagon levels
      observed in patients with cirrhosis. In addition, these data support the
      hypothesis that hyperglucagonaemia may contribute, at least in part, to the
      pathogenesis of peripheral arterial vasodilatation in cirrhosis with portal
      hypertension.

PMID- 8743914
TI  - Primary sclerosing cholangitis: an experience from India.
AB  - Primary sclerosing cholangitis (PSC) is considered to be rare in India. The aim
      of the present study was to investigate the incidence, clinical profile and
      outcome of PSC seen in a tertiary care centre. Over a period of 10 years (July,
      1984-June, 1994) 18 patients of PSC were diagnosed at cholangiography (14
      patients by endoscopic retrograde cholangiopancreatography, two patients by
      percutaneous transhepatic cholangiography and two patients by both methods). The
      presence of secondary causes, such as choledocholithiasis, biliary tract surgery,
      congenital biliary tract anomalies, cholangiocarcinoma and pancreatic diseases,
      were excluded. These patients were evaluated retrospectively with respect to
      their clinical presentation, radiological findings, presence of associated
      idiopathic ulcerative colitis (IUC), treatment instituted and outcome. The mean
      (+/- s.d.) age at diagnosis of PSC was 39.0 (+/- 16.1) years with a male:female
      ratio of 1.57:1. Nine (50%) patients had associated IUC. The diagnosis of the IUC
      preceded that of PSC in all but one case. Fifteen (83.3%) patients had
      cholestatic jaundice at presentation, while three (16.7%) patients had
      asymptomatic rise of alkaline phosphatase. Three (16.7%) patients had recurrent
      cholangitis and five (27.8%) patients developed portal hypertension during the
      course of the disease. At cholangiography, intrahepatic radicles were involved in
      all and extrahepatic radicles in 12 (66.6%) cases. Patients were managed with
      steroids (n = 7), colchicine (n = 3), ursodeoxycholic acid (UDCA; n = 2) and
      methotrexate (n = 1), along with symptomatic measures. Mean duration of follow up
      available in 11 (61%) patients was 20.1 months (range: 1 month-8 years). Four
      (36.4%) patients died. Steroids and colchicine did not have any effect while the
      one patient on UDCA and one on methotrexate showed improvement. In conclusion, in
      India PSC does not seem to be a rare entity. Its clinical profile and outcome are
      somewhat similar to those seen in Western countries.

PMID- 8743915
TI  - Case report: paucity of interlobular bile ducts in Chinese children.
AB  - Sixteen Chinese children with cholestasis since early infancy were diagnosed to
      have paucity of interlobular bile ducts (PILBD) or its equivalent. Twelve
      children belonged to the syndromic group of PILBD and four children belonged to
      the non-syndromic group. A definite histological diagnosis of bile duct paucity
      was established in only two children (aged 4 and 9 months) during the first
      percutaneous needle biopsy. In the remaining 14 children a varying degree of bile
      duct destruction was evident in the follow up percutaneous or wedge liver
      biopsies. The evolving changes were characterized by inflammatory infiltration
      near or at the ductal wall, the presence of dysmorphic ductules, the degeneration
      of ductal epithelia and a progressive decrease of interlobular bile ducts. Of 10
      children who underwent laparotomy for definite diagnosis, kasai operation was
      performed in two of them. In the syndromic PILBD group, all children, including
      two paired siblings, had at least three of five major clinical features.
      Hypoplasia of the extrahepatic biliary tree was found in five children and
      atresia of the extrahepatic bile duct was found in one. Three of six children
      studied were shown, by polymerase chain reaction, to have cytomegalovirus
      infection in the liver. This study demonstrates that bile duct paucity is a
      result of progressive bile duct destruction. A definitive diagnosis is difficult
      to make in early infancy. Thus, the careful evaluation of extrahepatic features
      in cholestatic children and follow-up liver biopsies are indicated. Although the
      pathogenetic mechanism of PILBD is unknown, bile duct destruction is the common
      pathway leading to paucity of bile ducts irrespective of syndromic or non
      syndromic types.

PMID- 8743917
TI  - Differential effects between tauroursodeoxycholic and taurochenodeoxycholic acids
      in hepatic fibrosis: an assessment by primary cultured Ito and Kupffer cells from
      the rat liver.
AB  - The pathogenesis of hepatic fibrosis in cholestasis is still unknown, except for
      endotoxaemia. There is a possibility that the elevation of serum bile acids in
      cholestasis may play an important role in hepatic fibrogenesis due to a reaction
      to perisinusoidal cells, such as Ito or Kupffer cells. To assess the effects of
      bile acids, we investigated the cell proliferation and collagen formation of
      primary cultured Ito cells that were incubated with a Kupffer cell conditioned
      medium (KCCM) treated with either taurochenodeoxycholic acid (TCDCA) or
      tauroursodeoxycholic acid (TUDCA) in short-term (8 h) or long-term (48 h)
      cultures. KCCM treated with TCDCA (100 mumol/L) but not with TUDCA increased cell
      proliferation of Ito cells in short-term cultures and also partially elevated
      collagen formation by Ito cells in long-term cultures. The release of tumour
      necrosis factor-alpha (TNF alpha) from Kupffer cells was increased by TCDCA in
      short-term cultures, but not in long-term cultures. The release of transforming
      growth factor-beta 1 (TGF beta 1) from Kupffer cells was increased by TCDCA in
      long-term cultures, but not in the short-term cultures. TUDCA showed no
      significant effect on the release of TNF alpha and TGF beta 1 from Kupffer cells.
      TUDCA or TCDCA itself showed no direct effect on the cell proliferation and
      collagen formation of Ito cells. In conclusion, these findings are thus
      considered to show the potentially important role of TCDCA on the development of
      hepatic fibrosis in the early phase of cholestasis without endotoxaemia.

PMID- 8743916
TI  - Serum markers for fibrosis and plasma transforming growth factor-beta 1 in
      patients with hepatocellular carcinoma in comparison with patients with liver
      cirrhosis.
AB  - In order to elucidate collagen metabolism in hepatocellular carcinoma (HCC)
      tissue, we compared levels of different potential markers of collagen metabolism
      and plasma transforming growth factor-beta 1 in patients with HCC and in patients
      with liver cirrhosis. Serum levels of prolyl hydroxylase and the tissue inhibitor
      of metalloproteinase-1 in patients with HCC were significantly higher than those
      in patients with liver cirrhosis and increased with the size of the HCC tumour,
      whereas the serum levels of procollagen type III propeptide and type IV collagen
      7S domain were similar in the two groups. In HCC, the increased plasma
      transforming growth factor-beta 1 levels were closely correlated with serum
      levels of prolyl hydroxylase and the tissue inhibitor of metalloproteinase-1.
      These findings suggest that, in HCC tissue, the intracellular biosynthesis of
      collagen is enhanced, whereas the secretion of procollagen is disturbed and the
      degradation of collagen is suppressed by the excess production of the tissue
      inhibitor of metalloproteinase-1. The results also suggest that plasma
      transforming growth factor-beta 1 plays an important role in the altered
      metabolism of collagen in HCC.

PMID- 8743918
TI  - Clinical significance of serum hyaluronan in patients with chronic viral liver
      disease.
AB  - In order to elucidate the clinical significance of serum hyaluronan in chronic
      viral hepatitis, serum hyaluronan concentrations were measured using a sandwich
      enzyme binding assay in 115 patients with chronic viral hepatitis. These findings
      were examined in relation to the results of laboratory liver tests, levels of
      serum markers for fibrosis and liver histological findings. Serum hyaluronan
      levels increased with the progress of liver disease, particularly in liver
      cirrhosis. There were no significant differences in serum hyaluronan levels among
      the cirrhotic patients according to Child's grade. Multivariate analysis showed
      that the significant independent predictors of serum hyaluronan were serum
      aspartate aminotransferase (P = 0.020), serum alanine aminotransferase (P =
      0.008), serum cholinesterase (P < 0.001), particularly serum type IV collagen 7S
      domain (P < 0.0001), and the histological degree of liver fibrosis (P < 0.0001).
      These findings suggest that elevated serum hyaluronan levels are closely related
      to the severity of liver fibrosis. We assessed the predictive value of serum
      hyaluronan in differentiating cirrhosis from chronic hepatitis, constructing
      receiver operating curves; we found that serum hyaluronan was a better test for
      diagnosing cirrhosis than serum type IV collagen 7S domain and laboratory liver
      tests.

PMID- 8743919
TI  - Review: regulation of liver regeneration by pro-inflammatory cytokines.
AB  - The liver has tremendous regenerative capacity. This distinguishes it from other
      vital organs (e.g. the brain, heart and lungs) that cannot replace functional
      tissue once it has been destroyed. Although hepatocytes rarely proliferate in the
      healthy adult liver, virtually all surviving hepatocytes replicate at least once
      after 70% partial hepatectomy. Therefore, partial liver resection has been used
      to characterize mechanisms that regulate liver regeneration. Residual hepatocytes
      up-regulate both proliferative and liver-specific gene expression in order to
      preserve tissue specific function. In addition, hepatocyte proliferation is
      tightly co-ordinated to complement regenerative responses in hepatic non
      parenchymal cells (e.g. endothelia, biliary epithelia, stellate and Kupffer
      cells), so that the entire organ can be reconstituted within days. Studies with
      neutralizing antibodies to tumour necrosis factor-alpha (TNF) clearly demonstrate
      that, after partial hepatectomy, TNF promotes liver cell proliferation. The
      present review focuses on the regulation of the hepatocyte proliferative response
      by pro-inflammatory cytokines.

PMID- 8743920
TI  - Treatment with a novel lipid A analogue, FS-112, and partial hepatectomy causes
      submassive liver necrosis and impaired liver regeneration in mice.
AB  - A novel experimental model of submassive liver necrosis with impaired
      regeneration has been established. A novel lipid A analogue, FS-112, was injected
      intravenously into male BALB/c mice, followed 2 days later by a 70% partial
      hepatectomy. Over the next 9 days, mice became severely jaundiced, with a peak
      total bilirubin (TBil) concentration of (mean +/- s.d.) 12.9 +/- 2.1 mg/dL 7 days
      postoperatively. In contrast, the TBil concentration in vehicle-treated mice
      remained less than 2 mg/dL. Significant elevations of L-alanine:2-oxoglutarate
      aminotransferase (ALT) were also observed 3-7 days after the operation in mice
      pretreated with FS-112, compared with mice pretreated with the vehicle.
      Submassive liver necrosis was observed with extensive mononuclear cell
      infiltration in mice treated with FS-112 and subjected to partial hepatectomy.
      Furthermore, both the BrdU and the proliferating cell nuclear antigen (PCNA)
      labelling index (LI) 1 day following partial hepatectomy in mice pretreated with
      FS-112 (8.6 +/- 4.3 and 7.9 +/- 4.2%, respectively) were significantly lower than
      levels in vehicle-treated mice (25.8 +/- 3.8 and 26.5 +/- 10.5%, respectively).
      The time course of changes in the BrdU LI in liver specimens from mice treated
      with both FS-112 and partial hepatectomy did not increase, even 3, 5, and 7 days
      postoperatively. Excellent liver regeneration with a PCNA LI 10-fold higher than
      the resting level was observed in mice treated with D-galactosamine
      hydrochloride. These results strongly suggest that this animal model of
      submassive liver necrosis may be suitable for clarifying the mechanisms of
      impaired liver cell regeneration often seen in fulminant hepatitis.

PMID- 8743921
TI  - Distribution of peptide-containing nerve fibres in achalasia of the oesophagus.
AB  - In this study the innervation of the normal human oesophagus was compared with
      samples taken from 12 patients undergoing Heller's cardiomyotomy for achalasia.
      The distribution of all nerve fibres in the oesophageal wall was revealed by
      immunoreactivity to neuron specific enolase and subpopulations of nerve fibres
      were revealed by immunoreactivity to vasoactive intestinal peptide, neuropeptide
      Y, enkephalin and substance P. In healthy oesophagus, many nerve fibres
      immunoreactive for vasoactive intestinal peptide and neuropeptide Y were present
      in the circular and longitudinal muscle layers of the oesophageal wall and in the
      cardia of the stomach, whereas fibres immunoreactive for enkephalin and substance
      P were uncommon. Neuropeptide Y-reactive fibres were commonly seen around blood
      vessels. In the myenteric plexus cell bodies reactive for vasoactive intestinal
      peptide and neuropeptide Y were prevalent, as were varicose and non-varicose
      fibres. In contrast, samples from patients with achalasia revealed few nerve
      fibres immunoreactive for vasoactive intestinal peptide or neuropeptide Y in
      either circular or longitudinal muscle, suggesting damage to the inhibitory motor
      neurons to the muscle layers. Very few fibres were found that were reactive for
      neuron-specific enolase, indicating that other fibre population (e.g. excitatory
      cholinergic motor neurons) are also damaged in achalasia. These abnormalities
      were observed in biopsies from both the constricted and dilated portions of the
      oesophagus, but the pattern of innervation in the gastric cardia was normal.
      Myenteric ganglion cells were seen in the oesophagus in only two patients and
      varicose nerve fibres in the myenteric plexus were uncommon. Neuropeptide Y
      reactive perivascular nerve fibres were still found in achalasia as well as non
      varicose nerve fibres in the myenteric plexus. These findings indicate damage to
      all intrinsic neurons in the oesophageal wall in achalasia; however, extrinsic
      nerve fibres appear to be intact.

PMID- 8743922
TI  - Detection of duodenal fluid in the oesophagus with a sodium ion selective
      electrode.
AB  - The assessment of duodeno-oesophageal reflux is difficult as, until recently, no
      technique has been readily available for continuous ambulatory monitoring. A
      sodium ion selective electrode placed in the stomach has been previously shown to
      detect duodenogastric reflux by using sodium as a marker. This relies on the
      difference in sodium concentration between gastric (5-60 mmol/L) and duodenal,
      biliary and pancreatic (150 mmol/L) fluids. In this pilot study to assess the
      efficacy of the electrode in the distal oesophagus, eight subjects without
      symptomatic gastro-oesophageal reflux and eight subjects with known
      duodenogastric reflux were studied. Thirty millilitre volumes of varying sodium
      solutions (40, 80, 100 and 140 mmol/L) were swallowed to assess the response of
      the electrode to sodium ions. In both groups, this revealed a constant and
      reproducible rise in response with increasing concentration (P < 0.0001). The
      stomachs of subjects with duodenogastric reflux were aspirated via a nasogastric
      tube to obtain 12 different samples of gastric fluid. This was assayed for sodium
      and bile acid concentration. The fluid was then reinfused as a 30 mL bolus into
      the oesophagus through a tube to simulate oesophageal reflux. A rise equivalent
      to 40-72 mmol/L Na+ was recorded by the electrode in response to samples that
      contained 58-81 mmol/L Na+ and 0.4-16 mmol/L bile acids, recorded by quantitative
      analysis, and a response of up to 20 mmol/L Na+ was recorded by the electrode to
      sodium concentrations < 49 mmol/L and bile acid concentrations of 0.005-0.6
      mmol/L. The response was appropriate to the assayed bile acid concentration in
      all but one sample. The sodium ion selective electrode responds to bile
      containing fluids introduced into the oesophagus. Further investigation is
      warranted to determine its ability to measure duodeno-oesophageal reflux
      continuously.

PMID- 8743923
TI  - Risk factors for pancreatic cancer in orientals.
AB  - In order to assess what the risk factors for patients with pancreatic cancer (PC)
      in Taiwan are, a retrospective study was undertaken among 282 consecutively
      enrolled inpatients with confirmed pancreatic cancer within the past 5 years. For
      comparison, 282 age- and sex-matched controls were consecutively enrolled. A
      history of smoking, consumption of alcohol, diabetes mellitus, cholecystectomy
      and gastric surgery were thoroughly reviewed. Smoking and diabetes mellitus were
      very common among patients with pancreatic cancer compared with controls (P <
      0.01). A significant linear trend towards an increased odds ratios (OR) for the
      development of PC with a higher level of smoking was seen (P < 0.001). Diabetes
      mellitus (DM) also exhibited an increased risk (OR: 2.84; P < 0.01), while the
      risk still existed among those patients who had a diabetic history of more than 3
      years. Among 129 histologically established PC patients, smoking remained as a
      risk factor for PC, while the linear trend with an increasing OR with increasing
      levels of smoking was confirmed again (P < 0.01). DM, particularly over the long
      term, was also a risk factor for those histologically established PC patients. In
      summary, cigarette smoking and existing diabetes mellitus are probable risk
      factors for the development of pancreatic cancer in Taiwan.

PMID- 8743924
TI  - Serum procarboxypeptidase B, amylase and lipase in chronic renal failure.
AB  - Procarboxypeptidase B (human pancreas-specific protein) has been reported to be a
      good serum marker for the diagnosis of acute pancreatitis. The current study was
      conducted in order to evaluate the frequency and degree of elevated serum levels
      of procarboxypeptidase B in chronic renal failure and their correlations with
      serum levels of amylase, lipase and renal function tests. Blood samples were
      taken from 84 asymptomatic patients with chronic renal failure, including 34
      patients with periodical haemodialysis and 50 patients without haemodialysis.
      Serum levels of procarboxypeptidase B, amylase, lipase, creatinine and blood urea
      nitrogen were measured. Serum levels of procarboxypeptidase B in 84 patients were
      63.4 +/- 5.5 micrograms/L significantly greater than the figure of 29.6 +/- 1.6
      micrograms/L in healthy adults in our previous report (P < 0.0001). There was a
      significant difference in serum levels of PCPB between patients with and without
      haemodialysis (78.0 +/- 9.4 vs 53.6 +/- 6.3 micrograms/L; P < 0.01). The
      frequencies of elevated serum levels of procarboxypeptidase B, amylase and lipase
      greater than upper normal limits were 27.4, 35.7 and 26.2%, respectively. The
      frequencies of elevated PCPB in patients with and without haemodialysis were 38.2
      and 20%, respectively. Only one patient had a serum procarboxypeptidase B level
      greater than three-fold the upper normal limit. A significant correlation was
      found between procarboxypeptidase B and lipase (r = 0.785; P < 0.0001). No
      significant correlation was noted between procarboxypeptidase B vs amylase or
      renal function tests. In conclusion, in patients with chronic renal failure, the
      elevation of serum procarboxypeptidase B is as common as the elevations of other
      pancreatic enzymes.

PMID- 8743925
TI  - The Cathlocator: a novel non-radiological method for the localization of enteral
      tubes.
AB  - Safe placement of nasogastric tubes requires reliable positioning of the tip of
      the tube within the stomach. Radiology and aspiration are currently used to
      confirm tube position, but suffer from significant problems of cost and efficacy,
      respectively. We have developed a novel method to locate the position of a
      catheter tip within the body, using the detection of low energy electromagnetic
      field generated in a coil located in the catheter with an external hand-held unit
      (Cathlocator). In vitro, the unit detected the distance of the coil from the
      detector with an accuracy of 0.1 cm over a range of 4-12 cm. In vivo studies were
      performed in 11 healthy volunteers using a purpose-built manometric assembly that
      incorporated the signal generating coil in its tip. In all subjects the
      Cathlocator showed the position of the signal generating coil to be cranial to
      the xiphisternum when manometric and transmucosal potential difference criteria
      showed it to be located above the lower oesophageal sphincter. When the coil was
      within the stomach, the Cathlocator identified its position within the
      epigastric, umbilical and left hypochondrial regions of the abdomen. The distance
      of the coil from the surface was significantly greater when in the duodenum mean
      (+/- s.e.m. 7.6 +/- 0.3 cm; P < 0.001) and oesophagus (8.6 +/- 0.2 cm; P < 0.002)
      than the stomach (5.0 +/- 0.4 cm). In one subject studied twice there was a close
      correlation between the location and depth measured by the device on each
      occasion. The Cathlocator is a novel non-radiological device that has the
      potential to be useful in the placement of gastrointestinal catheters.

PMID- 8743926
TI  - An assembled electrogastrographic device to examine the meal effect on gastric
      slow wave.
AB  - We have assembled an electrogastrographic device based on the main components of
      amplifiers, a band-pass filter, an analogue/digital converter, low band-pass
      digital filters and a personal computer. The analysis software uses
      autoregressive moving average modelling to compute the frequency of slow waves
      and uses fast Fourier transformation for power spectral computation. Twenty
      healthy young male volunteers were enrolled in the study to test meal-elicited
      responses of the slow wave. Subjects underwent a 15 min recording while fasting
      and then a standard breakfast, which included 250 mL milk and a cake with a total
      of 1.45 kj, was ingested within 5 min. The post-prandial 15 min recording was
      immediately resumed after the meal. A slight but significant increase in the
      frequency of slow waves was seen in post-prandial measurement (mean +/- s.d.,
      0.0506 +/- 0.0005 vs 0.0497 +/- 0.0005 Hz; P < 0.0001). Moreover, a significant
      enhancement of the power of slow waves was elicited following the meal (36.0 +/-
      3.1 vs 27.6 +/- 3.1 dB; P < 0.0001). We conclude that this assembled
      electrogastrographic device is a reliable means of monitoring gastric
      myoelectrical activity because the phenomenon of post-prandial responses of slow
      waves in either frequency or power is well demonstrated.

PMID- 8743927
TI  - Paediatric liver transplantation: a 10 year experience in Taiwan.
AB  - Between March 1984 and August 1994, 13 orthotopic liver transplantations were
      performed in 13 patients < or = 25 years of age. The indications included
      Wilson's disease (n = 7), biliary atresia (n = 4), choledochal cyst (n = 1) and
      hepatitis C cirrhosis (n = 1). Technical variants included full-size (n = 11),
      reduced-size (n = 1) and living-related (n = 1) liver transplantation. These
      recent technical innovations have offered an expanded donor pool for earlier
      transplantation, shorter waiting times and excellent quality grafts. Surgical
      complications occurred in six patients; all required additional surgery. Biliary
      complications were encountered more commonly in our earlier patients. Our
      actuarial patient and graft survival rate is 92% at 2 years. The long-term follow
      up of our liver-transplanted Wilson's disease patients provides confirmatory
      evidence that orthotopic liver transplantation cures the underlying metabolic
      defect with complete normalization of biochemical abnormalities of copper
      metabolism, reversal of neurological impairments and the disappearance of Kayser
      Fleischer corneal rings. The high rate of patient survival and excellent
      rehabilitation indicate that with prudent clinical judgement, liver
      transplantation can be achieved with an acceptable rate of morbidity, mortality
      and cost in a setting where manpower and donor organs are very limited.

PMID- 8743928
TI  - Chronic liver disease in children on long-term parenteral nutrition.
AB  - Use of long-term total parenteral nutrition (TPN) is often presumed to be
      associated with serious hepatic dysfunction. In this retrospective study, we
      reviewed the complete charts of patients who had received TPN for more than 2.5
      years, starting in infancy or childhood, for evidence of liver dysfunction. There
      were 16 male and 10 female patients with a total of 254.5 patient years on TPN.
      Seventeen patients have been on TPN since birth or early infancy. Thirteen of 26
      patients derive > or = 90% of their calorie intake from TPN. Six patients had
      hepatomegaly; two of them also had splenomegaly. Twenty-one patients had normal
      transaminases, nine have had past episodes of raised enzymes ranging from 2.5 to
      7.5 times normal. Seventeen patients always had normal bilirubin levels, five had
      past episodes of hyperbilirubinaemia, while four patients had persistently raised
      bilirubin levels (range 1.5-20.7 g/dl). Alkaline phosphatase was normal for age
      in all patients except two. Hepatic synthetic function, as measured by albumin,
      pre-albumin levels and prothrombin time, was within the normal range in all
      patients except one. Liver biopsies were performed in eight patients. Two
      biopsies showed cirrhosis, one showed chronic active hepatitis (CAH) with
      cholestasis, two patients had fibrosis, one showed cholestasis and two biopsies
      were normal. One patient with cirrhosis and one with CAH were positive for
      hepatitis C antibody. Another asymptomatic patient was positive for hepatitis B.
      Only the patient with CAH had hepatic decompensation. We conclude that clinical
      hepatic failure is uncommon in our group of patients on long-term TPN for 2.5
      years or more. Cirrhosis and fibrosis, when found, could not be solely attributed
      to TPN.

PMID- 8743929
TI  - Pre- and postoperative nutritional care in liver transplantation in children.
AB  - Orthotopic liver transplantation (OLT) is now a definitive treatment option for
      most cases of endstage liver disease (ESLD) in children. Efforts now focus on
      active supportive treatment to maintain, if not improve, the patient's clinical
      status before OLT and to ensure normal patterns of growth and development after
      OLT. Malnutrition adversely affects the outcome of OLT and is probably the single
      area in pre-operative management where the largest potential improvement can be
      made. Our studies indicate significant abnormalities of protein energy metabolism
      and body composition in children referred for OLT. We have shown that the use of
      enteral formulae, enriched with branched-chain amino acids, have significant
      advantages. Other adjunctive therapy, such as growth hormone, is the subject of
      current investigation. Following transplantation, catch-up weight and growth does
      occur with the advent of normal liver function, but patients at continuing risk
      for undernutrition, such as those with rejection and/or chronic infection, need
      to be targeted for specific nutritional therapy.

PMID- 8743930
TI  - Mycotoxins in foods in Africa.

PMID- 8743931
TI  - Partial purification and characterization of an esterase from Fusarium
      sporotrichioides.
AB  - Kinetics analysis of the growth of Fusarium sporotrichioides T-424 at 15 degrees
      C and 25 degrees C in liquid culture for 35 days revealed that production of
      deacetylated trichothecenes was associated with an increased activity in fungal
      esterases. High temperature (25 degrees C) favored enzyme production and enhanced
      esterase activity. Electrophoresis of crude extracts from the mycelia of F.
      sporotrichioides T-424 with carboxylesterase staining revealed that several
      esterases were produced by the fungus. Four carboxylesterase isoenzymes (I-IV)
      were separated on a DEAE-Sephadex anion exchange column. Type (III) esterase,
      having activities with the substrate 4-nitrophenylacetate and acetanilide, as
      well as hydrolytic activity for T-2 toxin and acetyl-T-2 toxin, was partially
      purified with ammonium sulfate precipitation, immunoaffinity column
      chromatography, and DEAE-Sephadex A-50 chromatography. The esterase (III) had a
      molecular weight around 68 kDa in SDS-PAGE. For the deacylation of T-2 toxin and
      acetyl-T-2 toxin, type (III) esterase had a high specificity for the acetyl group
      at the C-3 and C-4 positions. The Km values for acetyl-T-2 and T-2 toxin were
      found to be 41.35 microM and 0.38 microM, respectively. The Km value for the
      acetyl group at C-3 is 110 times greater than for that at C-4.

PMID- 8743932
TI  - Comparison of detection methods for trichothecenes produced by Fusarium
      sporotrichioides on fodder and grains at different air humidities.
AB  - Growth and toxin production of a highly toxic strain of Fusarium sporotrichioides
      Sherb were studied on oat and wheat grains and on straw under experimental
      conditions, in which relative humidity (RH) of air was regulated. The materials
      were incubated at three different RH levels at a range of 84-100%. F.
      sporotrichioides grew well on oat and wheat grains at RH 97-100% but grew less
      well at RH 84-88% and on straw. Toxin production was measured with three
      biological toxicity tests (cytotoxicity test, dermotoxicity test, and yeast cell
      toxicity test), with chemical analysis, and T-2 ELISA assay. Cytotoxicity and
      production of trichothecene mycotoxins were detected in all the samples incubated
      at all three RH levels. On oat and wheat grains, T-2 toxin, neosolaniol, and
      diacetoxyscirpenol were found, and on straw T-2 toxin, HT-2 toxin, neosolaniol,
      and T-2 tetraol were determined. In the T-2 ELISA assay, all material samples
      were found to contain T-2 toxin. The cytotoxicity test was the most sensitive
      method for detecting biological toxicity of samples inoculated with fungus. The T
      2 ELISA assay and chemical analysis were about equally sensitive to detect T-2
      toxin in samples.

PMID- 8743933
TI  - Fluoroacetate content of some species of the toxic Australian plant genus,
      Gastrolobium, and its environmental persistence.
AB  - Gas chromatography confirmed the relatively high concentrations of fluoroacetate
      found in toxic Gastrolobiums, a genus of indigenous Australian plants.
      Fluoroacetate concentration in these plants ranged from 0.1 to 3875 micrograms/g
      (ppm) dry weight, with young leaves and flowers containing the highest
      concentrations. However, there was considerable intrastand variation between
      individual plants of at least two species with coefficients of variation ranging
      from 94% to 129%. Despite the high concentrations of fluoroacetate in many
      species, only one of nine soil samples collected from beneath these plants
      contained fluoroacetate. None of the 16 water samples collected from nearby
      streams and catchment dams contained fluoroacetate. This suggests that
      fluoroacetate does not persist in this environment. Fluoroacetate was also found
      in the genus Nemcia, and very low levels of fluoroacetate (ng/g) were detected in
      the foodstuffs, tea and guar gum. The latter indicates that other plant species
      may produce biologically insignificant amounts of fluoroacetate.

PMID- 8743934
TI  - (2,4-cis)-asimicinone and (2,4-trans)-asimicinone: two novel bioactive
      ketolactone acetogenins from Asimina triloba (Annonaceae).
AB  - Two novel bioactive ketolactone Annonaceous acetogenins, (2,4-cis)-asimicinone
      (1) and (2,4-trans)-asimicinone (2), have been isolated from Asimina triloba
      (Annonaceae) by bioactivity directed fractionation. The separation of these two
      epimeric compounds was achieved by HPLC methods using a Si gel normal phase
      column eluted with acetone in hexane gradients. The assignments of cis or trans
      stereochemistry of the ketolactone moieties were made on the bases of 1H-1H COSY
      and NOESY experiments. 1 and 2 showed selective cytotoxicities against A-549
      (human lung cancer) and MCF-7 (human breast cancer) cell lines with ED50 values
      as low as < 10(-7) micrograms/ml with 2 being the more active isomer.

PMID- 8743935
TI  - Effects of the naturally occurring arginine analogues indospicine and canavanine
      on nitric oxide mediated functions in aortic endothelium and peritoneal
      macrophages.
AB  - The ability of the naturally occurring non-protein toxic amino acids indospicine
      and canavanine to inhibit nitric oxide synthesis was tested in isolated rat aorta
      and cultured rat peritoneal macrophages. Both compounds inhibited acetylcholine
      induced relaxation of rat aorta contracted with noradrenaline, a process mediated
      by nitric oxide generated in vascular endothelium. Nitric oxide is generated in
      vascular endothelium from arginine by a constitutive nitric oxide synthase.
      Indospicine and canavanine also increased superoxide mediated reduction of
      cytochrome c by phorbol myristate acetate stimulated rat peritoneal macrophages.
      The increase in superoxide under these conditions was due to decreased nitric
      oxide synthesis. Macrophage synthesis of nitric oxide is mediated by an inducible
      form of nitric oxide synthase. It is concluded that indospicine and canavanine
      are inhibitors of constitutive and inducible nitric oxide synthases and it is
      suggested that the toxicity associated with these compounds could be related to
      this activity.

PMID- 8743936
TI  - Effects of ochratoxin A on the rat immune system after perinatal exposure.
AB  - Effects on the immune system after perinatal exposure to ochratoxin A (OA) were
      studied in Sprague-Dawley rats after single or repeated exposure of the dams. In
      a short-term study, dams with litters were given a single dose of OA (0, 10, 50
      or 250 micrograms/kg body weight) on day 11 of lactation. The effects on cell
      numbers in spleen and thymus and on the mitogen responses of lymphocytes were
      evaluated in the suckling pups on day 14 of lactation. The proliferative response
      of splenocytes to the T-cell mitogen Concanavalin A (Con A) was significantly
      stimulated in pups from dams given 10 or 50 micrograms OA/kg body weight as
      compared to control pups. In addition, proliferation of thymocytes in response to
      Con A was stimulated in pups from dams exposed to 50 micrograms OA/kg body
      weight. In a long-term, cross-fostering study comparing pre- and postnatal
      exposure, half of the dams received 50 micrograms OA/kg body weight 5 days a week
      by gastric intubation 2 weeks before mating, during gestation and then 7 days a
      week until weaning. Effects on immune parameters were studied in the pups on day
      14 of lactation and at 13 weeks of age. Suppressed mitogenic responses were seen
      to both lipopolysaccharide (LPS) and Con A in prenatally exposed pups sampled on
      day 14 of lactation. At 13 weeks the response of splenocytes to LPS was still
      impaired. The primary antibody response to a viral antigen was also lower in the
      prenatally exposed pups than in the control pups. These effects on the immune
      response were not seen in the groups of pups exposed postnatally or both pre- and
      postnatally, although blood concentrations of OA were higher in these groups at
      the time of the first sampling. This indicates that the decrease in proliferation
      and antibody production resulted from prenatal modulation of the immune system.
      The results show that prenatal exposure to relatively low doses of OA may induce
      immunosuppression. In contrast, short-term exposure of suckling pups to OA via
      the milk stimulates the proliferative responses of lymphocytes to polyclonal
      activation.

PMID- 8743937
TI  - Establishment and characterization of conditionally immortalized cells from the
      mouse urogenital ridge.
AB  - Cell cultures from the urogenital ridge have been established to facilitate the
      study of the regulation and downstream interactions of Sry in mammalian sex
      determination. Cells have been explanted from transgenic mice carrying a
      temperature sensitive SV40 large T-antigen, and established in ongoing cultures.
      Analysis of the cells in these cultures at the electron microscope level reveals
      multiple cell types that compare to the cell types found in vivo during this
      period of development. Primordial germ cells, that are simultaneously explanted
      in the course of these experiments, also survive in culture. The explants undergo
      a morphogenetic organization into branching cord-like structures when cells are
      trypsinized and plated in extracellular matrix (Matrigel). We analyzed the
      expression of a number of molecular markers of the fetal gonad during monolayer
      culture, during in vitro morphogenesis in Matrigel, and in clonal lines derived
      from the complex explants. This analysis included Sry which is found to be
      expressed in some cultures from XY urogenital ridges that have been maintained
      for as long as 8 months.

PMID- 8743938
TI  - Meiotic spindle organization in fertilized Drosophila oocyte: presence of
      centrosomal components in the meiotic apparatus.
AB  - We examined spindle reorganization during the completion of meiosis in fertilized
      and unfertilized oocytes of Drosophila using indirect immunofluorescence and
      laser scanning confocal microscopy. The results defined a complex pathway of
      spindle assembly during resumption of meiosis, and revealed a transient array of
      microtubules radiating from the equatorial region of the spindle towards discrete
      foci in the egg cortex. A monastral array of microtubules was observed between
      twin metaphase II spindles in fertilized and unfertilized eggs. The microtubules
      originated from disk-shaped material stained with Rb188 antibody specific for an
      antigen associated with the centrosome of Drosophila embryos. The Drosophila egg,
      therefore, contains a maternal pool of centrosomal components undetectable in
      mature inactivated oocytes. These components nucleate microtubules in a monastral
      array after activation, but are unable to organize bipolar spindles.

PMID- 8743939
TI  - Metallopeptidase inhibitors induce an up-regulation of endothelin-converting
      enzyme levels and its redistribution from the plasma membrane to an intracellular
      compartment.
AB  - Endothelin-converting enzyme is a phosphoramidon-sensitive membrane
      metallopeptidase that catalyses the final step in biosynthesis of the potent
      vasoactive endothelin peptides. Immunomagnetic separation technology and
      immunohistochemistry have been used to demonstrate the co-localisation of
      endothelin-converting enzyme with the established ectoenzyme, aminopeptidase N,
      on the surface of endothelial cells. Unlike aminopeptidase N, however, endothelin
      converting enzyme is seen to associate in clusters on the plasma membrane which
      can be distinguished from caveolae both biochemically and immunologically. Pre
      treatment of endothelial cells with the metallopeptidase inhibitors
      phosphoramidon or thiorphan in the range 0.01-100 microM produced a dose
      dependent increase in the levels of endothelin-converting enzyme protein and its
      accumulation in an intracellular compartment. No corresponding change in the
      levels of endothelin-converting enzyme-1 mRNA was detected under these
      conditions, nor in the levels of the closely related metalloenzyme, endopeptidase
      24.11. The phosphoramidon and thiorphan-dependent increase is not due to direct
      inhibition of endothelin-converting enzyme not endopeptidase-24.11 but, rather,
      to an inhibition of the selective turnover of endothelin-converting enzyme
      protein.

PMID- 8743940
TI  - Differential localization of Na+/H+ exchanger isoforms (NHE1 and NHE3) in
      polarized epithelial cell lines.
AB  - Na+/H+ exchangers (NHEs) are transporters that exchange sodium and proton ions
      across the plasma membrane at the expense of their chemical gradient. In higher
      eukaryotes these transporters exist as multiple specialized isoforms. For
      example, NHE1, the ubiquitously expressed form is a major pH-regulating system
      whereas the epithelial NHE3 isoform is specialized in transepithelial Na+
      transport. NHE1 and NHE3 can be very well distinguished pharmacologically with
      the HOE694 specific inhibitor and immunologically with specific polyclonal and
      monoclonal antibodies. With these molecular tools we investigated the specific
      steady state expression of the two NHE isoforms in polarized epithelial cells in
      culture. Endogenous NHE3 in OK cells or NHE3-VSVG transfected in either OK or
      MDCK cells showed an exclusive expression of the transporter at the apical
      membrane. Overexpression of NHE3 did not result in any spill over on the basal
      lateral side. These results obtained by functional measurement of NHE3 activity
      were fully consistent with its detection only at the apical side by
      immunofluorescence and confocal microscopy. By contrast, using the same cells,
      the same culture conditions and the same detection methods, we clearly detected
      NHE1 at both specialized membranes of four different polarized epithelial cell
      lines. Furthermore, biotinylation of cell surface proteins of MDCK, OK and HT-29
      cells followed by immunoprecipitation of NHE1 revealed expression of the
      transporter at both sides of the polarized epithelial cells. Interestingly, the
      cell surface expression correlated well with the corresponding NHE1 activities.
      In addition, immunodetection by fluorescence microscopy was found to be
      qualitatively consistent with the above-reported results. We therefore conclude
      that the epithelial and more specialized NHE3 isoform is exclusively restricted
      to the apical side of epithelial cells. In marked contrast, both endogenous or
      ectopically expressed NHE1 isoform, have the capacity to be expressed in both the
      apical and basal lateral membranes of polarized cells in cultures.

PMID- 8743941
TI  - Integrin dynamics on the tail region of migrating fibroblasts.
AB  - Cell migration is a complex process that can be considered as a repeated cycle of
      lamellipod extension and attachment, cytoskeletal contraction, and tail
      detachment. While lamellipodial and cytoskeletal phenomena are currently the
      focus of considerable research on cell migration, under many conditions
      locomotion appears to be rate-limited by events at the cell rear, especially
      release of cell/substratum adhesions. To study the mechanism of tail detachment,
      we have developed a novel experimental system that permits observation of
      integrin dynamics on the ventral surface of migrating fibroblasts.
      Photoactivatable caged fluorescein is coupled to a non-adhesion-perturbing anti
      avian-beta 1 integrin subunit antibody, which labels integrins on chicken
      fibroblasts migrating on a laminin-coated glass coverslip. Ultraviolet light is
      focused through a pinhole to photoactivate the caged fluorophore in a 10-micron
      diameter spot at the rear of a polarized cell. The fate of integrins initially
      present in this spot is monitored using a cooled CCD camera to follow the
      movement of fluorescent intensity as a function of time over a 2 to 3 hour
      period. We find that a substantial fraction of the integrins is left behind on
      the substratum as the cell detaches and locomotes, while another fraction
      collects into vesicles which are transported along the cell body as the cell
      migrates. As aggregates rip from the cell membrane, the integrin-cytoskeletal
      bonds are preferentially fractured resulting in 81 +/- 15% of the integrin
      remaining attached to the substratum. We additionally find that adhesions
      sometimes disperse into integrins which can form new adhesions at other locations
      in the cell. Adhesions along the cell edge can release from the substrate and
      translocate with the cell. They either disperse in the cell membrane, rip from
      the cell membrane and remain attached to the substratum, or form a new aggregate.
      These observations indicate that the behavior of integrins at the cell rear is
      much more dynamic than previously appreciated, suggesting that an important locus
      for regulation of motility may reside in this region.

PMID- 8743942
TI  - MT-MMP, the cell surface activator of proMMP-2 (pro-gelatinase A), is expressed
      with its substrate in mouse tissue during embryogenesis.
AB  - Matrix metalloproteinases (MMPs), which degrade the components of the
      extracellular matrix, are key enzymes involved in the tissue remodeling of
      multicellular organisms. Since MMPs are secreted as inactive zymogens (pro-MMPs),
      they have to be activated to function. We identified a membrane-type MMP (MT-MMP)
      that activated proMMP-2 (pro-gelatinase A = 72 kDa type IV pro-collagenase) and
      described its expression on the invasive tumor cell surface. In this study we
      further examined the expression and role of MT-MMP in the activation of proMMP-2
      during mouse embryogenesis. Northern blotting demonstrated that MT-MMP expression
      was increased together with that of MMP-2 and its inhibitor gene, TIMP-2, in
      embryos depending upon the number of days after gestation, and decreased with
      maturation after birth. In situ hybridization and immunohistochemistry localized
      MT-MMP mRNA and protein in the cells of ossifying tissues where both MMP-2 and
      TIMP-2 were expressed. Activated MMP-2 was detected by gelatin zymography in the
      lysates prepared from the micro dissected tissues that expressed the three genes.
      The activation rate of proMMP-2 was proportional to the expression of MMP-2 and
      MT-MMP. These results indicated that proMMP-2 activation through its activator,
      MT-MMP, is a physiological system used by organisms to initiate tissue remodeling
      on the cell surface.

PMID- 8743943
TI  - The kinesin-like protein CENP-E is kinetochore-associated throughout poleward
      chromosome segregation during anaphase-A.
AB  - The kinesin-like protein CENP-E transiently associates with kinetochores
      following nuclear envelope breakdown in late prophase, remains bound throughout
      metaphase, but sometime after anaphase onset it releases and by telophase becomes
      bound to interzonal microtubules of the mitotic spindle. Inhibition of poleward
      chromosome movement in vitro by CENP-E antibodies and association of CENP-E with
      minus-end directed microtubule motility in vitro have combined to suggest a key
      role for CENP-E as an anaphase chromosome motor. For this to be plausible in vivo
      depends on whether CENP-E remains kinetochore associated during anaphase. Using
      Indian muntjac cells whose seven chromosomes have large, easily tracked
      kinetochores, we now show that CENP-E is kinetochore-associated throughout the
      entirety of anaphase-A (poleward chromosome movement), relocating gradually
      during spindle elongation (anaphase-B) to the interzonal microtubules. These
      observations support roles for CENP-E not only in the initial alignment of
      chromosomes at metaphase and in spindle elongation in anaphase-B, but also in
      poleward chromosome movement in anaphase-A.

PMID- 8743944
TI  - Organelle motility and metabolism in axons vs dendrites of cultured hippocampal
      neurons.
AB  - Regional regulation of organelle transport seems likely to play an important role
      in establishing and maintaining distinct axonal and dendritic domains in neurons,
      and in managing differences in local metabolic demands. In addition, known
      differences in microtubule polarity and organization between axons and dendrites
      along with the directional selectivity of microtubule-based motor proteins
      suggest that patterns of organelle transport may differ in these two process
      types. To test this hypothesis, we compared the patterns of movement of different
      organelle classes in axons and different dendritic regions of cultured embryonic
      rat hippocampal neurons. We first examined the net direction of organelle
      transport in axons, proximal dendrites and distal dendrites by video-enhanced
      phase-contrast microscopy. We found significant regional variation in the net
      transport of large phase-dense vesicular organelles: they exhibited net
      retrograde transport in axons and distal dendrites, whereas they moved equally in
      both directions in proximal dendrites. No significant regional variation was
      found in the net transport of mitochondria or macropinosomes. Analysis of
      individual organelle motility revealed three additional differences in organelle
      transport between the two process types. First, in addition to the difference in
      net transport direction, the large phase-dense organelles exhibited more
      persistent changes in direction in proximal dendrites where microtubule polarity
      is mixed than in axons where microtubule polarity is uniform. Second, while the
      net direction of mitochondrial transport was similar in both processes, twice as
      many mitochondria were motile in axons than in dendrites. Third, the mean
      excursion length of moving mitochondria was significantly longer in axons than in
      dendrites. To determine whether there were regional differences in metabolic
      activity that might account for these motility differences, we labeled
      mitochondria with the vital dye, JC-1, which reveals differences in mitochondrial
      transmembrane potential. Staining of neurons with this dye revealed a greater
      proportion of highly charged, more metabolically active, mitochondria in
      dendrites than in axons. Together, our data reveal differences in organelle
      motility and metabolic properties in axons and dendrites of cultured hippocampal
      neurons.

PMID- 8743945
TI  - A high molecular mass non-muscle tropomyosin isoform stimulates retrograde
      organelle transport.
AB  - Although non-muscle tropomyosins (TM) have been implicated in various cellular
      functions, such as stabilization of actin filaments and possibly regulation of
      organelle transport, their physiological role is still poorly understood. We have
      probed the role of a high molecular mass isoform of human fibroblast TM, hTM3, in
      regulating organelle transport by microinjecting an excess amount of bacterially
      expressed protein into normal rat kidney (NRK) epithelial cells. The
      microinjection induced the dramatic retrograde translocation of organelles into
      the perinuclear area. Microinjection of hTM5, a low molecular mass isoform had no
      effect on organelle distribution. Fluorescent staining indicated that hTM3
      injection stimulated the retrograde movement of both mitochondria and lysosomes.
      Moreover, both myosin I and cytoplasmic dynein were found to redistribute with
      the translocated organelles to the perinuclear area, indicating that these
      organelles were able to move along both microtubules and actin filaments. The
      involvement of microtubules was further suggested by the partial inhibition of
      hTM3-induced organelle movement by the microtubule-depolymerizing drug
      nocodazole. Our results, along with previous genetic and antibody microinjection
      studies, suggest that hTM3 may be involved in the regulation of organelle
      transport.

PMID- 8743946
TI  - Trafficking of cell-surface amyloid beta-protein precursor. I. Secretion,
      endocytosis and recycling as detected by labeled monoclonal antibody.
AB  - Amyloid beta-protein, the principal constituent of amyloid fibrils found in
      senile plaques and blood vessels in Alzheimer's disease, is constitutively
      produced and released into medium of cultured cells. Amyloid beta-protein is
      derived by proteolysis of the beta-amyloid precursor protein by unclear
      mechanisms. Beta-amyloid precursor protein is a transmembrane protein which can
      be processed to release a large secretory product or processed in the
      endosomal/lysosomal pathway without secretion. Previous studies have shown that
      from the cell surface, beta-amyloid precursor protein may be released after
      cleavage or internalized without cleavage, the latter in a pathway that both
      produces amyloid beta-protein and also targets some molecules to the lysosomal
      compartment. Analysis of beta-amyloid precursor protein trafficking is confounded
      by the concomitant secretion and internalization of molecules from the cell
      surface. To address this issue, we developed an assay, based on the binding of
      radioiodinated monoclonal antibody, to measure the release and internalization of
      cell surface beta-amyloid precursor protein in transfected cells. With this
      approach, we showed that surface beta-amyloid precursor protein is either rapidly
      released or internalized, such that the duration at the cell surface is very
      short. Approximately 30% of cell surface beta-amyloid precursor protein molecules
      are released. Following internalization, a fraction of molecules are recycled
      while the majority of molecules are rapidly sorted to the lysosomal compartment
      for degradation When the C terminus of beta-amyloid precursor protein is deleted,
      secretion is increased by approximately 2.5-fold as compared to wild-type
      molecules. There is concomitant decrease in internalization in these mutant
      molecules as well as prolongation of the resident time on the cell surface. This
      observation is consistent with recent evidence that signals within the
      cytoplasmic domain mediate beta-amyloid precursor protein internalization.

PMID- 8743947
TI  - Trafficking of cell-surface amyloid beta-protein precursor. II. Endocytosis,
      recycling and lysosomal targeting detected by immunolocalization.
AB  - Amyloid beta-protein (A beta) is a proteolytic fragment of the amyloid beta
      protein precursor (beta PP). Progressive cerebral deposition of A beta is an
      early and invariant feature of Alzheimer's disease. The cellular trafficking of
      beta PP is of particular interest because understanding the production of A beta
      requires a comprehensive elucidation of the metabolic pathways of this protein.
      In addition, beta PP is a type I integral membrane glycoprotein that belongs to a
      class of molecules with both full length and secreted products. Recent evidence
      suggests that beta PP can be processed in an endosomal/lysosomal pathway. In the
      latter organelles, a number of beta PP carboxy-terminal derivatives are found,
      but the precise pathway and kinetics of beta PP trafficking from the cell surface
      remain unclear. To address these questions, we visualized directly the beta PP
      internalization pathway by following the localization and distribution of beta PP
      monoclonal antibodies added to intact beta PP-transfected Chinese hamster ovary
      cells. Using immunofluorescence and immunoelectron microscopy, beta PP was shown
      to be rapidly internalized via coated pits and vesicles, after which the
      molecules were transported to endosomes, prelysosomes, and lysosomes. Using a
      modified immunodetection protocol, we demonstrated the rapid recycling of
      endocytosed beta PP to the cell surface and its ultimate targeting to lysosomes.
      Because we recently found that endocytosis of cell surface beta PP is one route
      for the constitutive production of A beta, the recycling pathway for cell surface
      beta PP demonstrated here is a probable route for production of the critical A
      beta fragment.

PMID- 8743948
TI  - Antisense RNA inactivation of gene expression of a cell-cell adhesion protein
      (gp64) in the cellular slime mold Polysphondylium pallidum.
AB  - The gp64 protein of Polysphondylium pallidum has been shown to mediate EDTA
      stable cell-cell adhesion. To explore the functional role of gp64, we made an
      antisense RNA expression construct designed to prevent the gene expression of
      gp64; the construct was introduced into P. pallidum cells and the transformants
      were characterised. The antisense RNA-expressing clone L3mc2 which had just been
      harvested at the growth phase tended to re-form in aggregates smaller in size
      than did the parental cells in either the presence or absence of 10 mM EDTA. In
      contrast, 6.5-hour starved L3mc2 cells remained considerably dissociated from
      each other after 5 minutes gyrating, although aggregation gradually increased by
      50% during a further 55 minutes gyrating in the presence of 10 mM EDTA.
      Correspondingly, L3mc2 lacked specifically the cell-cell adhesion protein, gp64.
      We therefore conclude that the gp64 protein is involved in forming the EDTA
      resistant cell-cell contact. In spite of the absence of gp64, L3mc2 exhibited
      normal developmental processes, a fact which demonstrates that another cell-cell
      adhesion system exists in the development of Polysphondylium. This is the first
      report in which an antisense RNA technique was successfully applied to
      Polysphondylium.

PMID- 8743949
TI  - Keratin 19 as a biochemical marker of skin stem cells in vivo and in vitro:
      keratin 19 expressing cells are differentially localized in function of anatomic
      sites, and their number varies with donor age and culture stage.
AB  - This study was undertaken to evaluate keratin 19 (K19) as a biochemical marker
      for skin stem cells in order to address some long standing questions concerning
      these cells in the field of cutaneous biology. We first used the well-established
      mouse model enabling us to identify skin stem cells as [3H]thymidine-label
      retaining cells. A site directed antibody was raised against a synthetic peptide
      of K19. It reacted specifically with a 40 kDa protein (K19) on immunoblotting. It
      labelled the bulge area of the outer root sheath on mouse skin by
      immunohistochemistry. Double-labelling revealed that K19-positive-cells were also
      [3H]thymidine-label-retaining cells, suggesting that K19 is a marker for skin
      stem cells of hair follicles. K19-expression was then used to investigate the
      variation in mouse and human skin stem cells as a function of body site, donor
      age and culture time. K19 was expressed in the hair follicle and absent from the
      interfollicular epidermis at hairy sites (except for some K18 coexpressing Merkel
      cells). In contrast, at glabrous sites, K19-positive-cells were in deep epidermal
      rete ridges. K19 expressing cells also contained high levels of alpha 3 beta 1
      integrin. The proportion of K19-positive-cells was greater in newborn than older
      foreskins. This correlated with keratinocyte culture lifespan variation with
      donor age. Moreover, it could explain clinical observations that children heal
      faster than adults. In conclusion, K19 expression in skin provides an additional
      tool to allow further characterization of skin stem cells under normal and
      pathological conditions in situ and in vitro.

PMID- 8743950
TI  - Transcription regulation of alpha B-crystallin in astrocytes: analysis of HSF and
      AP1 activation by different types of physiological stress.
AB  - The coordinated cellular responses to physiological stress are known to be
      effected in part by the activation of heat-shock factor 1, a transcriptional
      activator protein capable of binding to, and inducing transcription from genes
      containing heat shock elements. Other stress responsive signal transduction
      pathways also exist including the stress activated protein kinase cascade that
      regulates the activity of the transcription factor AP1. We have examined the
      expression of the low molecular stress proteins, heat shock protein 27 and alpha
      B-crystallin in astrocytes in response to physiological stress of different types
      and asked what component of this induction is effected at the transcriptional
      level and whether activation of heat shock factor 1 and AP1 might account for
      these events. We have found that stress regulated induction of alpha B-crystallin
      has a strong transcriptional component and that it may be effected by at least
      two different transcriptional mechanisms. In one set of phenomena, represented
      here by cadmium exposure, alpha B-crystallin and heat shock protein 27 are
      coordinately regulated and this occurs in the presence of activated heat shock
      factor 1. In the second series of phenomena, represented here by hypertonic
      stress, alpha B-crystallin is induced in the absence of heat shock factor
      activation and in the absence of any corresponding change in heat shock protein
      27 expression. Although hypertonic stress does activate an AP1-like binding
      activity, the AP1 consensus binding site in the alpha B-crystallin promoter does
      not appear to be a target for this hypertonic stress inducible activity. These
      data suggest that the hypertonic stress response is effected through a heat shock
      factor independent mechanism and that hypertonic stress regulated induction of
      alpha B-crystallin does not directly depend on the SAPK pathway and AP1 activity.

PMID- 8743951
TI  - The vacuolar proton pump of Dictyostelium discoideum: molecular cloning and
      analysis of the 100 kDa subunit.
AB  - The vacuolar proton pump is a highly-conserved multimeric enzyme that catalyzes
      the translocation of protons across the membranes of eukaryotic cells. Its
      largest subunit (95-116 kDa) occurs in tissue and organelle-specific isoforms and
      thus may be involved in targeting the enzyme or modulating its function. In
      amoebae of Dictyostelium discoideum, proton pumps with a 100 kDa subunit are
      found in membranes of the contractile vacuole complex, an osmoregulatory
      organelle. We cloned the cDNA that encodes this 100 kDa protein and found that
      its sequence predicts a protein 45% identical (68% similar) to the corresponding
      mammalian proton pump subunit. Like the mammalian protein, the predicted
      Dictyostelium sequence contains six possible transmembrane domains and a single
      consensus sequence for N-linked glycosylation. Southern blot analysis detected
      only a single gene, which was designated vatM. Using genomic DNA and degenerate
      oligonucleotides based on conserved regions of the protein as primers, we
      generated products by polymerase chain reaction that included highly variable
      regions of this protein family. The cloned products were identical in nucleotide
      sequence to vatM, arguing that Dictyostelium cells contain only a single isoform
      of this proton pump subunit. Consistent with this interpretation, the amino acid
      sequences of peptides derived from a protein associated with endosomal membranes
      (Adessu et al. (1995) J. Cell Sci. 108, 3331-3337) match the predicted sequence
      of the protein encoded by vatM. Thus, a single isoform of the 100 kDa proton pump
      subunit appears to serve in both the contractile vacuole system and the
      endosomal/lysosomal system of Dictyostelium, arguing that this subunit is not
      responsible for regulating the differing abundance and function of proton pumps
      in these two compartments. Gene targeting experiments suggest that this subunit
      plays important (possibly essential) roles in Dictyostelium cells.

PMID- 8743952
TI  - SCO-spondin: a new member of the thrombospondin family secreted by the
      subcommissural organ is a candidate in the modulation of neuronal aggregation.
AB  - A number of cues are known to influence neuronal development including growth
      factors, cell-adhesion molecules, components of the extracellular matrix and
      guidance molecules. In this study, we present molecular and functional evidence
      that SCO-spondin, a novel relative of the thrombospondin family, could also be
      involved in neuronal development by modulating cell aggregative mechanisms. SCO
      spondin corresponds to glycoproteins secreted by the subcommissural organ (SCO),
      an ependymal differentiation of the vertebrate brain located at the entrance to
      the Sylvian aqueduct. A cDNA clone of 2.6 kb, isolated from a bovine SCO cDNA
      library, was shown to be specifically and highly expressed in the bovine SCO by
      in situ hybridization and was subsequently sequenced. Analysis of the deduced
      amino acid sequence reveals the presence of four conserved domains known as
      thrombospondin (TSP) type I repeats. To account for the homology with
      thrombospondins and F-spondin, this secreted glycoprotein was called SCO-spondin.
      Two potent binding sites to glycosaminoglycan (BBXB) and to cytokine (TXWSXWS)
      are also found in the TSP type I repeats. The deduced amino acid sequence
      exhibits three other conserved domains called low density lipoprotein (LDL)
      receptor type A repeats. The possibility of SCO-spondin involvement in neuronal
      development as a component of the extracellular matrix is discussed regarding
      these molecular features. The idea of a modulation of cell-cell and/or cell
      matrix interaction is further supported by the anti-aggregative effect observed
      on cultured neuronal cells of material solubilized from Reissner's fiber. That
      Reissner's fiber, the condensed secretory product of the SCO present along the
      whole spinal cord can be a potent morphogenetical structure is an important
      concept for the analysis of the molecular mechanisms leading to spinal cord
      differentiation.

PMID- 8743953
TI  - Presence and expression of G2 cyclins in the coelenterate hydra.
AB  - In hydra all cell-cycle control occurs in the G2/M transition. Cyclins acting at
      this restriction point in the cell cycle belong to the cyclin A and B families.
      In agreement with this we isolated cDNAs coding for a cyclin A and a cyclin B
      from the multiheaded mutant of Chlorohydra viridissima and a cyclin B from Hydra
      vulgaris. The two B-type cyclins from hydra show 85.6% identity at the amino acid
      level, and 84.8% at the nucleotide level. The relatedness is less extensive than
      that found for mammals, e.g. human and mouse, and is evidence that the two hydra
      species diverged early in evolution. From each hydra species only one B-type
      cyclin was found, showing equal relatedness to the B1 and B2 subtypes of cyclins,
      hinting at a role as common ancestor before the split into B1 and B2 cyclins
      occurred. All three hydra cyclins contain regulation signals typical for G2/M
      cyclins, such as a ubiquitin destruction box at the amino terminus, needed for
      rapid degradation of the protein, and translation and polyadenylation elements in
      the 3' untranslated region to regulate RNA storage and RNA degradation. In hydra
      cell-cycle times vary depending on feeding regime and growth conditions. Cyclin B
      RNA expression was found to precede the daily mitotic rhythm induced by feeding.
      During head regeneration cyclin B expression showed the expected drop early
      during regeneration and an increase later. At the cellular level strongest
      expression of cyclin B RNA and protein was detected in interstitial cells which
      possess with one day the shortest cell-cycle time in hydra. Epithelial cells with
      a three-day cell-cycle rhythm showed variable, and differentiated cells no cyclin
      B expression. Regions of hydra containing high numbers of proliferating cells,
      such as developing buds exhibited elevated levels of cyclin B expression.

PMID- 8743954
TI  - Activation of the Xenopus cyclin degradation machinery by full-length cyclin A.
AB  - The entry into mitosis is dependent on the activation of mitotic forms of cdc2
      kinase. In many cell types, cyclin A-associated kinase activity peaks just prior
      to that of cyclin B, although the precise role of cyclin A-associated kinase in
      the entry into mitosis is still unclear. Previous work has suggested that while
      cyclin B is capable of triggering cyclin destruction in Xenopus cell-free
      systems, cyclin A-associated kinase is not able to support this function. Here we
      have expressed a full-length human cyclin A in Escherichia coli and purified the
      protein to homogeneity by virtue of an N-terminal histidine tag. We have found
      that when added to Xenopus cell-free extracts free of cyclin B and incapable of
      protein synthesis, the temporal pattern of cyclin A-associated cdc2 kinase
      activity showed distinct differences that were dependent on the concentration of
      cyclin A added. When cyclin A was added to a concentration that generated levels
      of cdc2 kinase activity capable of inducing nuclear envelope breakdown, the
      histone H1 kinase activity profile was bi-phasic, consisting of an activation
      phase followed by an inactivation phase. Inactivation was found to be due to
      cyclin destruction, which was prevented by mos protein. Cyclin destruction was
      followed by nuclear reassembly and an additional round of DNA replication,
      indicating that there is no protein synthesis requirement for DNA replication in
      this embryonic system. It has been suggested that the evolutionary recruitment of
      cyclin A into an S phase function may have necessitated the loss of an original
      mitotic ability to activate the cyclin destruction pathway. The results presented
      here indicate that cyclin A has not lost the ability to activate its own
      destruction and that cyclin A-mediated activation of the cyclin destruction
      pathway permitted destruction of cyclin B1 as well as cyclin A, indicating that
      there are not distinct cyclin A and cyclin B destruction pathways. Thus the
      ordered progression of the cell cycle requires the careful titration of cyclin. A
      concentration in order to avoid activation of the cyclin destruction pathway
      before sufficient active cyclin B/cdc2 kinase has accumulated.

PMID- 8743955
TI  - Cytoplasmic accumulation of cdc25B phosphatase in mitosis triggers centrosomal
      microtubule nucleation in HeLa cells.
AB  - The formation of the mitotic spindle is an essential prerequisite for successful
      mitosis. The dramatic changes in the level of microtubule (Mt) nucleation at the
      centrosomes and Mt dynamics that occur in prophase are presumed to be initiated
      through the activity of cdc2/cyclin B. Here we present data that the cdc25B
      isoform functions to activate the cytoplasmic pool of cdc2/cyclin B responsible
      for these events. In contrast to cdc25C, cdc25B is present at low levels in HeLa
      cells during interphase, but sharply increases in prophase, when cdc25B
      accumulation in the cytoplasm correlates with prophase spindle formation.
      Overexpression of wild type and dominant negative mutants of cdc25B and cdc25C
      shows that prophase Mt nucleation is a consequence of cytoplasmic cdc25B
      activity, and that cdc25C regulates nuclear G2/M events. Our data also suggest
      that the functional status of the centrosome can regulate nuclear mitotic events.

PMID- 8743956
TI  - MAP2d promotes bundling and stabilization of both microtubules and
      microfilaments.
AB  - Two low molecular weight MAP2 variants have been described, MAP2c and MAP2d.
      These variants are produced from a single gene by alternative splicing, and in
      their C-terminal regions contain, respectively, 3 and 4 tandem repeats, some of
      which are known to be involved in binding to microtubules. Substantial
      differences in the developmental expression pattern of MAP2c and MAP2d suggest
      they have different functions in neural cells. In order to investigate the
      respective roles of these MAP2 variants, we have analyzed the effects of MAP2c
      and MAP2d expression on microtubule and microfilament organization in transiently
      transfected cells. Our results show that both variants stabilize microtubules,
      but only MAP2d stabilizes microfilaments.

PMID- 8743957
TI  - Oxidative stress is involved in the UV activation of p53.
AB  - In many vertebrate cells exposure to ultraviolet light lead to a dramatic
      increase in the cellular levels of the tumour suppressor protein p53, followed by
      a biological response of either growth arrest or programmed cell death.
      Ultraviolet light can be absorbed directly by cellular macromolecules, leading to
      photochemical modification of DNA and proteins. Additionally, it also causes free
      radical formation, resulting in oxidative stress. Whereas ultraviolet light and
      ionizing radiation both induce DNA lesions which trigger an activation of the p53
      pathway, the magnitude of the p53 response elicited by ionizing radiation is
      comparatively low. Following irradiation with ultraviolet light two populations
      of p53-reactive cells are induced: a population accumulating high levels of p53
      protein and a population with comparatively low levels of p53, similar in
      magnitude to the p53 response following ionizing radiation. Pretreatment of cells
      with N-acetylcysteine, an agent known to counteract oxidative stress, attenuates
      the cellular p53 response to ultraviolet light by reducing the number of cells
      with high p53 levels but does not affect the response to ionizing radiation. We
      demonstrate that N-acetylcysteine pretreatment does not prevent the inflicted DNA
      damage and therefore conclude that oxidative stress is a causative agent in the
      ultraviolet light activation of the p53 pathway.

PMID- 8743958
TI  - Immunofluorescence studies of human fibroblasts demonstrate the presence of the
      complex of elongation factor-1 beta gamma delta in the endoplasmic reticulum.
AB  - The eukaryotic elongation factor-1 (EF-1) consists of four subunits, EF-1 alpha,
      EF-1 beta, EF-1 gamma and EF-1 delta which induce efficient transfer of aminoacyl
      tRNA to the ribosome. In this process EF-1 alpha.GTP acts as the carrier of the
      aminoacyl-tRNA on its way to the ribosome. After release of aminoacyl-tRNA to the
      ribosome under concomitant hydrolysis of GTP, the inactive EF-1 alpha.GDP form is
      recycled to EF-1 alpha.GTP by EF-1 beta gamma delta. In eukaryotic cells the
      concentration of EF-1 alpha exceeds that of the complex beta gamma delta by a
      factor of 5-10. In order to delineate the intracellular localization of the
      different subunits of EF-1, antibodies against the EF-1 subunits have been
      elicited and indirect immunofluorescence microscopy experiments were performed.
      In human fibroblasts, the guanine nucleotide exchange part of EF-1, EF-1 beta
      gamma delta, was found to co-localize with the endoplasmic reticulum (ER),
      displaying a distinct fine-structure in its staining pattern. The guanine
      nucleotide-binding subunit of EF-1, EF-1 alpha, shows a more diffuse distribution
      throughout the cytoplasm and is, in addition, associated with the nucleus.

PMID- 8743959
TI  - Collagen expression in chicken tibial dyschondroplasia.
AB  - Collagen expression in growth plate cartilage derived from broiler chickens with
      tibial dyschondroplasia was studied and compared with samples from unaffected
      birds. Normal growth plate contains 12% collagen (dry weight) and
      dyschondroplastic growth plate 19% collagen compared with articular cartilage,
      which contains 55%. Dyschondroplastic growth plate collagens were more resistant
      to extraction by pepsin treatment than were those from unaffected growth plate.
      Normal and dyschondroplastic growth plate cartilages contain similar amounts of
      type I collagen (5% of the total collagen) but dyschondroplastic growth plate
      cartilage contains slightly less type II and type XI collagens, and significantly
      more type X collagen (25% as compared to 11%) than in normal growth plate. The
      levels of the mature collagen cross-link, hydroxylysyl-pyridinoline, are very low
      in normal growth plate but are six times higher in dyschondroplastic lesions.
      Immunolocalisation studies show that there is little change to the normal
      patterns of collagen organisation in dyschondroplastic growth plate.
      Investigation of metalloproteinase activity showed there to be a reduction in MMP
      2 levels in dyschondroplastic growth plate compared to normal growth plate. In
      vitro studies on articular, normal growth plate and dyschondroplastic growth
      plate chondrocytes cultured in alginate or on plastic revealed differences
      between the cell types. When plated on plastic, articular chondrocytes rapidly
      assume a fibroblastic morphology. In contrast, normal growth plate chondrocytes
      retain their polygonal morphology whereas chondrocytes derived from
      dyschondroplastic cartilage initially exhibit both fibroblastic and polygonal
      phenotypes but gradually change to totally fibroblastic. These morphological
      changes are reflected by the collagen synthesis in vitro. Chondrocytes derived
      from normal articular cartilage synthesised collagen types I, II and X when
      cultured in alginate but type X synthesis was lost when cultured on plastic.
      Chondrocytes derived from normal growth plate cartilage synthesised predominantly
      type X collagen when cultured in either system. Chondrocytes derived from
      dyschondroplastic growth plate exhibited a similar phenotype to normal growth
      plate chondrocytes when cultured in alginate beads, but showed signs of
      dedifferentiation with reduced type X collagen and increased type I collagen when
      plated on plastic. These results suggest that the chondrocytes in
      dyschondroplastic growth plate cartilage are at a different stage of maturity
      than normal resulting in a cartilage that is failing to turn over at a normal
      rate.

PMID- 8743960
TI  - Rho stimulates tyrosine phosphorylation of focal adhesion kinase, p130 and
      paxillin.
AB  - The small GTP-binding protein Rho rapidly stimulates the formation of focal
      adhesions and actin stress fibres when microinjected into serum-starved Swiss 3T3
      fibroblasts. This response is inhibited by tyrosine kinase inhibitors. Addition
      of growth factors such as lysophosphatidic acid and bombesin to Swiss 3T3 cells
      stimulates a similar response, which is dependent on endogenous Rho proteins. To
      investigate signalling events regulated by Rho, we have scrape loaded Rho into
      serum-starved cells. Activated Rho stimulates the tyrosine phosphorylation of a
      number of proteins, including three proteins known to localise to focal
      adhesions, pp125FAK, p130 and paxillin. Rho-induced phosphorylation of pp125FAK,
      p130 and paxillin is observed in the absence of stress fibre formation and is,
      therefore, independent of Rho-induced actin polymerisation. We propose that the
      tyrosine kinase, pp125FAK, and the putative adapter proteins, paxillin and p130,
      are components of a Rho-regulated signal transduction pathway, and that these
      protein tyrosine phosphorylation events are likely to be important for the
      regulation of focal adhesion formation.

PMID- 8743961
TI  - Plakoglobin domains that define its association with the desmosomal cadherins and
      the classical cadherins: identification of unique and shared domains.
AB  - Two cell-cell junctions, the adherens junction and the desmosome, are prominent
      in epithelial cells. These junctions are composed of transmembrane cadherins
      which interact with cytoplasmic proteins that serve to link the cadherin to the
      cytoskeleton. One component of both adherens junctions and desmosomes is
      plakoglobin. In the adherens junction plakoglobin interacts with both the
      classical cadherin and with alpha-catenin. Alpha-catenin in turn interacts with
      microfilaments. The role plakoglobin plays in the desmosome is not well
      understood. Plakoglobin interacts with the desmosomal cadherins, but how and if
      this mediates interactions with the intermediate filament cytoskeleton is not
      known. Here we compare the domains of plakoglobin that allow it to associate with
      the desmosomal cadherins with those involved in interactions with the classical
      cadherins. We show that three sites on plakoglobin are involved in associations
      with the desmosomal cadherins. A domain near the N terminus is unique to the
      desmosomal cadherins and overlaps with the site that interacts with alpha
      catenin, suggesting that there may be competition between alpha-catenin and the
      desmosomal cadherins for interactions with plakoglobin. In addition, a central
      domain is shared with regions used by plakoglobin to associate with the classical
      cadherins. Finally, a domain near the C terminus is shown to strongly modulate
      the interactions with the desmosomal cadherins. This latter domain also
      contributes to the association of plakoglobin with the classical cadherins.

PMID- 8743962
TI  - Chromatin structure of the MMTV promoter and its changes during hormonal
      induction.
AB  - 1. The packaging of nuclear DNA in chromatin determines the conversion of the
      genetic information into a defined phenotype by influencing the availability of
      DNA sequences for interactions with regulatory proteins and transcription
      factors. 2. We have studied the influence of the first level of chromatin
      organization, the nucleosome, on the activity of the mouse mammary tumor virus
      (MMTV) promoter. The MMTV promoter is strongly transcribed in response to steroid
      hormones but is virtually silent in the absence of hormonal stimuli. Full
      hormonal induction requires binding of the hormone receptors to four hormone
      responsive elements (HREs), as well as binding of nuclear factor I (NFI) and the
      octamer transcription factor 1 (OTF-1 or Oct-1) to sites located between the HREs
      and the TATA box. A full loading with transcription factors cannot be achieved on
      free DNA due to steric hindrance between hormone receptor and NFI and between NFI
      and OTF-1. 3. The low basal activity of the MMTV promoter is most likely due to
      its organization in a positioned nucleosome. In the intact cell, as well in
      reconstituted chromatin, the regulatory region of the MMTV promoter is wrapped
      around a histone octamer in a precise rotational orientation, which permits
      access of the hormone receptors to only two of the four HREs, while precluding
      binding of NFI and OTF-1 to their respective sites. Upon hormone induction, the
      nucleosome is remodeled and the path of its DNA altered in a way which makes the
      nucleosomal dyad axis more accessible to DNase I and enables occupancy of all
      relevant sites: the four HREs, as well as the binding sites for NFI and OTF-1. 4.
      These results suggest that the nucleosomal organization of the MMTV promoter not
      only is responsible for the low activity prior to hormone treatment, but also may
      be a prerequisite for full loading with transcription factors after hormone
      induction. We conclude that the DNA contains topological information which
      modulates the expression of the genetic program.

PMID- 8743963
TI  - Gonadal and adrenal steroids regulate neurochemical and structural plasticity of
      the hippocampus via cellular mechanisms involving NMDA receptors.
AB  - 1. The hippocampus is an important brain structure for working and spatial memory
      in animals and humans, and it is also a vulnerable as well as plastic brain
      structure as far as sensitivity to epilepsy, ischemia, head trauma, stress, and
      aging. 2. The hippocampus is also a target brain area for the actions of hormones
      of the steroid/thyroid hormone family, which traditionally have been thought to
      work by regulating gene expression. "Genomic" actions of steroid hormones involve
      intracellular receptors, whereas "nongenomic" effects of steroids involve
      putative cell surface receptors. Although this distinction is valid, it does not
      go far enough in addressing the variety of mechanisms that steroid hormones use
      to produce their effects on cells. This is because cell surface receptors may
      signal changes in gene expression, while genomic actions sometimes affect
      neuronal excitability, often doing so quite rapidly. 3. Moreover, steroid
      hormones and neurotransmitters may operate together to produce effects, and
      sometimes these effects involve collaborations between groups of neurons. For
      example, a number of steroid actions in the hippocampus involve the
      coparticipation of excitatory amino acids. These interactions are evident for the
      regulation of synaptogenesis by estradiol in the CA1 pyramidal neurons of
      hippocampus and for the induction of dendritic atrophy of CA3 neurons by repeated
      stress as well as by glucocorticoid injections. In addition, neurogenesis in the
      adult and developing dentate gyrus is "contained" by adrenal steroids as well as
      by excitatory amino acids. In each of these three examples, NMDA receptors are
      involved. 4. These results not only point to a high degree of interdependency
      between certain neurotransmitters and the actions of steroid hormones, but also
      emphasize the degree to which structural plasticity is an important aspect of
      steroid hormone action in the adult as well as developing nervous system.

PMID- 8743964
TI  - Estrogenic control of preoptic area development in a carnivore, the ferret.
AB  - 1. Evidence is reviewed which shows that a sexually dimorphic nucleus located in
      the dorsomedial portion of the male ferret's preoptic area/anterior hypothalamus
      (POA/AH), called the male nucleus of the POA/AH (Mn-POA/AH), develops during
      fetal life in response to the action of estradiol, which is formed directly in
      the nervous system from circulating testosterone over the final quarter of a 41
      day gestation. 2. Results are summarized which establish that neurons which make
      up the Mn-POA/AH are born prior to the critical period of estradiol's action in
      the male brain. Other data show that some radial glial processes, visualized
      immunocytochemically using antibodies against GFAP, emanate from proliferative
      zones at the base of the lateral ventricles in a dorsal-ventral orientation,
      whereas other glial processes emanate laterally from proliferative zones lining
      the third ventricle. 3. We suggest that at least some neurons which constitute
      the dorsomedial POA/AH are born in proliferative zones surrounding the lateral
      ventricles, raising the question of whether estradiol acts in developing males to
      influence the migration of these neurons along radial glial guides into the Mn
      POA/AH. 4. Finally, evidence is summarized showing that excitotoxic lesions of
      the dorsomedial POA/AH enhance males' preference to approach and interact with
      another sexually active male, as opposed to an estrous female, when adult
      subjects are castrated and treated with estradiol benzoate. These data suggest
      that the sexually dimorphic Mn-POA/AH is an essential part of a CNS circuit which
      determines heterosexual partner preference in the male ferret.

PMID- 8743965
TI  - Steroid imprinting and modulation of sexual dimorphism in the luteinizing hormone
      releasing hormone neuronal system.
AB  - 1. Sex differences in the control of gonadotropin secretion and reproductive
      functions are a distinct characteristic in all mammalian species, including
      humans. Ovulation and cyclicity are among the most distinct neuroendocrine
      markers of female brain differentiation, along with sex behavioral traits that
      are also evident in different species. 2. The luteinizing hormone-releasing
      hormone (LHRH) neuronal system is the prime regulator of neuroendocrine events
      leading to ovulation and hormonal changes during the menstrual cycle and, as
      such, is the potential site where many of these sex differences may be expressed
      or, at the very least, integrated. However, until recently, no significant
      differences were seen in LHRH neurons between male and female brains, including
      cell number, pattern of distribution, and expression of message or peptide (LHRH)
      levels. 3. Recently, we reported that galanin (GAL), a brain-gut peptide, is
      coexpressed in LHRH neurons and that this coexpression is sexually dimorphic.
      When GAL is used as a marker for this neuronal system, it is clear that estradiol
      as well as progesterone profoundly affects the message and expression of the
      peptide and that this regulation, at least in rodents, is neonatally
      predetermined by gonadal steroid imprinting. 4. Changes in GAL expression and
      message can also be seen at puberty, during pregnancy and lactation, and in
      aging, all situations that affect the function of the LHRH neuronal system. Using
      an immortalized LHRH neuronal cell line (GT1) we have recently observed that
      these neurons express estrogen receptor (ER) and GAL and that estradiol can
      increase the expression of GAL, indicating functional activation of the
      endogenous ER.

PMID- 8743966
TI  - Progesterone as a neurosteroid: actions within the nervous system.
AB  - 1. Some progesterone is synthesized within both the central and the peripheral
      nervous systems, where it regulates neurotransmission and important glial
      functions, such as the formation of myelin. Progesterone can thus be designated a
      "neurosteroid." 2. Steroids act not only on the brain, but also on peripheral
      nerves, which offer many advantages to study the biological significance of
      locally produced neurosteroids: their remarkable plasticity and regenerative
      capacity and their relatively simple structure. 3. By using the regenerating
      mouse sciatic nerve as a model, we have shown that progesterone synthesized by
      rat Schwann cells promotes the formation of new myelin sheaths. Progesterone also
      increases the number of myelinated axons when added at a low concentration to
      cocultures of Schwann cells and sensory neurons. 4. These findings show a
      function on myelination for locally produced progesterone and suggest a new
      pharmacological approach of myelin repair.

PMID- 8743967
TI  - Neurosteroid modulation of native and recombinant GABAA receptors.
AB  - 1. The pioneering work of Hans Selye over 50 years ago demonstrated that certain
      steroid metabolites can produce a rapid depression of central nervous system
      activity. 2. Research during the last 10 years has established that such effects
      are mediated by a nongenomic and specific interaction of these steroids with the
      brain's major inhibitory receptor, the GABAA receptor. 3. Here we describe the
      molecular mechanism of action of such steroids and review attempts to define the
      steroid binding site on the receptor protein. The therapeutic potential of such
      neurosteroids is discussed.

PMID- 8743968
TI  - Membrane receptors for estrogen, progesterone, and testosterone in the rat brain:
      fantasy or reality.
AB  - 1. There are numerous circumstantial evidence supporting the concept that steroid
      hormones control cellular function by means other than the nuclear receptor
      steroid binding mechanism. It is the intent of this report to present evidence
      indicating that steroids bind to specific sites in neuronal membranes. 2. Some of
      the criteria to define steroid membrane receptors using steroid-BSA conjugates
      that can be radioiodinated to desired specific activity have been fulfilled for
      each of the three sex steroids using crude synaptosomal membrane preparations (P2
      fractions) from the CNS of female and male rats. Ligand binding for each of the
      three steroids indicate high-affinity and high-capacity sites with distinct brain
      selectivity and stereospecificity. For example, 17 beta-E-6-[125I]BSA binds
      hypothalamic P2 fractions (HYP-P2) with an estimated Kd of about 3 +/- 0.7 nM (X
      +/- SE; n = 3), whereas the cerebellum P2 (CB-P2) fractions bind the ligand with
      a Kd of 34 +/- 7 nM and, a Bmax of 3 and 42 pmol/mg protein, respectively.
      Estrogen and testosterone binding fit best a one-single site, while progesterone
      binding sites can be best represented by a two-binding site, one high-affinity
      (Kd = 1-2 nM) and one low affinity (Kd = 62 nM), in CB-P2 fractions from intact
      adult female rat brain. Kinetics studies for T-3-[125I]BSA indicate that the
      estimated Kd of 30 +/- 2 nM for the olfactory bulb P2 fractions (OB-P2) from male
      rats is in good agreement with Kd values computed from Scatchard-derived data
      using the LIGAND algorithm. 3. 17 beta-E-6-[125I]BSA binding sites are
      stereospecific and appears to be present as early as 5 days of age in both the OB
      and the CB-P2 fractions without changes during development. In contrast, P-6
      [125I]BSA binding sites are practically absent during days 5 and 12 and appear by
      day 22. 4. Finally, membrane receptor molecules for estrogen and progesterone
      have been isolated and purified by affinity chromatography and characterized by
      PAGE and Western blot. Microsequencing of one of the membrane estrogen binding
      proteins indicates that the high-affinity site corresponds to the OSCP subunit of
      the proton ATP synthase. 5. It remains to be determined if P and T also bind to
      this complex enzyme or if they bind to other subunits of the family of proton
      ATPases. Overall the data indicate that steroid hormones conjugated to BSA are
      important tools to study the "reality of membrane steroid receptors."

PMID- 8743969
TI  - The modulation of brain dopamine and GABAA receptors by estradiol: a clue for CNS
      changes occurring at menopause.
AB  - 1. Tardive dyskinesia is more important in postmenopausal women than men of
      comparable age and a peak of first episodes of schizophrenia is observed in
      postmenopausal women. The effect of ovariectomy (2 weeks or 3 months) in rats was
      investigated as a model of decreased gonadal function associated with menopause.
      2. Frontal cortex D1 receptor density and affinity were similar in intact male
      compared to intact female rats and progressively decreased in density with time
      after ovariectomy, with no change of affinity. Striatal D1 and D2 receptors also
      decreased in density after ovariectomy for both receptor subtypes, with no change
      of affinity. Striatal D1 receptor density and affinity were similar in intact
      male and female rats, whereas the density of D2 receptors was higher in females.
      Treatment with estradiol for 2 weeks restored the D2 but not the D1 receptor
      changes. 3. In the substantia nigra pars reticulata, striatum, nucleus accumbens,
      and entopeduncular nucleus, a progressive increase in [3H]flunitrazepam specific
      binding associated with GABAA receptors was observed as a function of time
      following ovariectomy; this was corrected with estradiol treatment. In contrast,
      the opposite was observed for [3H] flunitrazepam binding in the globus pallidus,
      where ovariectomy decreased binding, which was corrected with estradiol
      replacement therapy. 4. Low prefrontal cortex dopamine activity with implications
      of D1 receptors in negative symptoms of schizophrenia is hypothesized.
      Furthermore, GABAergic overactivity in the internal globus pallidus-substantia
      nigra pars reticulata complex is hypothesized in tardive dyskinesia. 5. The
      present data suggest that gonadal hormone withdrawal by reducing brain dopamine
      receptors and producing an imbalance of GABAA receptors in the output pathways of
      the striatum may predispose to schizophrenia and dyskinesia.

PMID- 8743970
TI  - Potential neuronal mechanisms of estrogen actions in synaptogenesis and synaptic
      plasticity.
AB  - 1. Studies conducted on the rat arcuate nucleus, an area involved in the
      development and control of LH and FSH secretion, have shown the existence of
      hormonally regulated developmental sex differences in synaptic patterns and
      estrogen-induced synaptic plasticity during adult life. Several questions raised
      by these findings are examined in this review: 2. The mechanisms of estrogen
      regulated developmental synaptogenesis. These include the role of glycocalyx
      glycoproteins in neuronal membranes, neural cell adhesion molecules, and insulin
      like growth factor I. 3. The relationship among circulating estrogen,
      gonadotropin levels, and hypothalamic synaptic plasticity. Recent evidence for
      the role of GABAergic and dopaminergic synaptic inputs and POMC projections from
      the arcuate nucleus to the GnRH cells is discussed. 4. The synaptologic basis of
      age-related failure of positive feedback. The role of the cumulative effect of
      repeated preovulatory synaptic retraction and reapplication cycles on sensescent
      constant estrus is analyzed.

PMID- 8743971
TI  - Gonadal steroids and astroglial plasticity.
AB  - 1. Recent evidence indicates that astroglia participate in the metabolism of
      gonadal hormones, in the synthesis of neurosteroids, and in the plastic responses
      of neurons to gonadal steroids. The role of astroglia on plastic responses of
      neural tissue to gonadal hormones and neurosteroids is examined in this review.
      2. Gonadal steroids and neurosteroids promote astroglia plasticity in several
      areas of the central nervous system, including the hypothalamus, the striatum,
      and the hippocampus. 3. Gonadal steroids and neurosteroids modulate astroglia
      proliferation and the formation of reactive astroglia after brain injury. 4.
      Astroglia is a source of trophic factors that may mediate effects of gonadal
      steroids on neural tissue. 5. Astroglia is involved in the promotion of synaptic
      plastic changes by gonadal hormones. 6. The effect of gonadal hormones on
      astroglial plasticity is dependent on specific membrane interactions with neurons
      and on the expression of the embryonic highly polysialylated isoform of the
      neural cell adhesion molecule on neuronal membranes. 7. In conclusion,
      coordinated responses of neurons and astroglia appear to be involved in the
      modulation of neural function and response to injury by gonadal hormones and
      neurosteroids.

PMID- 8743972
TI  - On the role of glucocorticoid receptors in brain plasticity.
AB  - 1. The mapping of glucocorticoid receptors (GR) in the rat central nervous system
      (CNS) has demonstrated their widespread presence in large numbers of nerve and
      glial cell populations also outside the classical stress regions. 2. The present
      paper summarizes the evidence that glucocorticoids via GR in the CNS can act as
      lifelong organizing signals from development to aging. The following examples are
      given. (a) In the prepubertal and adult offspring, prenatal corticosterone
      treatment can produce long-lasting changes in striatal dopaminergic
      communication. (b) In adulthood, the evidence suggests complex regulation by
      adrenocortical hormones of neurotrophic factors and their receptors in the
      hippocampal formation. (c) In aging, the strongly GR-immunoreactive pyramidal
      cell layer of the CA1 hippocampal area appears to be preferentially vulnerable to
      neurotoxic actions of glucocorticoids, especially in some rat strains. 3. Strong
      evidence suggests that each nerve cell in the CNS is supported by a trophic unit,
      consisting of other nerve cells and glial cells, blood vessels, and extracellular
      matrix molecules. Due to multiple actions on nerve and glial cell populations of
      the different trophic units, the glucocorticoids may exert either an overall
      trophic or a neurotoxic action. It seems likely that with increasing age, the
      endangering actions of glucocorticoids on nerve cells prevail over the
      neurotrophic ones, leading to reduced nerve cell survival in some trophic units.

PMID- 8743973
TI  - Neuroplastic changes in the hypothalamic arcuate nucleus: the estradiol effect is
      accompanied by increased exoendocytotic activity of neuronal membranes.
AB  - 1. In the rat hypothalamic arcuate nucleus, estradiol induces coordinated changes
      in the number of axosomatic synapses, the amount of glial ensheathing, and the
      ultrastructure of the membrane of neuronal somas. In the present study we used
      conventional electron microscopy and freeze-fracture to examine cellular
      mechanisms responsible for the estradiol-induced changes at the membrane level.
      2. In freeze-fracture replicas taken 10-60 min and 24 hr after injection of 17
      beta-estradiol to adult ovariectomized females, it was found that there was a
      rapid increase in the number of exoendocytotic images that reached a plateau by
      30 min. 3. In thin sections from animals injected 24 hr earlier we demonstrated a
      significant increase in coated vesicles in the periphery of the neurons and
      coated pits in the perikaryal membranes and decreased axosomatic synapses. 4. We
      conclude that these morphological alterations are signaling estrogen-induced
      transport and/or turnover of perikaryal membrane constituents and extracellular
      components which may affect interneuronal and neuroglial interactions.

PMID- 8743974
TI  - Oxidative injury to isolated rat pancreatic acinar cells vs. isolated zymogen
      granules.
AB  - This study compares the susceptibility of pancreatic acinar cells and zymogen
      granules against oxidative injury and analyzes the mechanisms involved. Zymogen
      granules and acinar cells, isolated from rat pancreas, were exposed to a reaction
      mixture containing xanthine oxidase, hypoxanthine, and chelated iron. Cell
      function and viability were assessed by various techniques. Trypsin activation
      was quantified by an Elisa for trypsinogen activating peptide. Integrity of
      granules was determined by release of amylase. The reaction mixture rapidly
      generated radicals as assessed by deoxyribose and luminol assays. This oxidative
      stress caused lysis of granules in a matter of minutes but significant cell death
      only after some hours. Nevertheless, radicals initiated intracellular
      vacuolization, morphological damage to zymogen granules and mitochondria,
      increase in trypsinogen activating peptide, and decrease in ATP already after 5
      30 min. Supramaximal caerulein concentrations also caused rapid trypsin
      activation. Addition of cells but not of granules reduced deoxyribose oxidation,
      suggesting that intact cells act as scavengers. Caerulein pretreatment only
      slightly increased the susceptibility of cells but markedly that of granules. In
      conclusion, isolated zymogen granules are markedly more susceptible to oxidative
      injury than intact acinar cells, in particular, in early stages of caerulein
      pancreatitis. The results show that oxidative stress causes a rapid trypsin
      activation that may contribute to cell damage by triggering autodigestion.
      Zymogen granules and mitochondria appear to be important targets of oxidative
      damage inside acinar cells. The series of intracellular events initiated by
      oxidative stress was similar to changes seen in early stages of pancreatitis.

PMID- 8743975
TI  - Lipid metabolite involvement in the activation of the human heme oxygenase-1
      gene.
AB  - Cellular effects of ultraviolet A (UVA) radiation include peroxidation of
      membrane lipids as well as a decrease in intracellular glutathione. We have
      investigated whether damage to membrane lipids is involved in the activation of
      the human heme oxygenase-1 gene by UVA. Irradiation of human skin fibroblasts in
      the presence of the lipophilic antioxidants, butylated hydroxytoluene and alpha
      tocopherol, enhances the UVA-induced HO-1 mRNA accumulation, suggesting that
      peroxidation of plasma membrane lipids is not involved. Furthermore, sodium
      ascorbate, which induces lipid peroxidation mainly in the plasma membrane,
      induces HO-1 mRNA to low levels only. The decrease in GSH by UVA radiation is not
      affected by the presence of the lipophilic antioxidants while ascorbate treatment
      increases the intracellular GSH by twofold above controls. These results indicate
      that peroxidation of internal membrane lipids, a decrease in the intracellular
      GSH levels and the integrity of the plasma membrane are all important for the UVA
      induction of heme oxygenase-1. Both nonenzymatic as well as enzymatic lipid
      peroxidation metabolites are inducers of heme oxygenase-1. The nonenzymatic lipid
      peroxidation product 4-hydroxynonenal induces heme oxygenase-1 mRNA up to 40-fold
      and the phospholipase metabolites diacylglycerol and arachidonic acid induce this
      mRNA by three-to sixfold above basal levels. We also demonstrate that the
      cyclooxygenase metabolites of arachidonic acid are important for the UVA
      activation of the heme oxygenase-1 gene.

PMID- 8743976
TI  - Lipid peroxidation products in human subretinal fluid.
AB  - The concentrations of thiobarbituric acid reacting substances (TBARS) and
      proteins in the subretinal fluid (SF) of patients undergoing retinal detachment
      surgery have been determined. We have tried to establish the correlations between
      these biochemical and other clinical features of these patients: evolution time
      of the retinal detachment, age, degree of myopia, and macular affection.
      Caucasian patients, 19 men and 19 women (57.42 +/- 12.85 average age, interval 20
      80) were randomly selected for this study. SF samples were obtained by puncture
      after scleral indentation. TBARS and protein concentrations were determined by
      the corresponding colorimetric assays. A linear correlation exists between TBARS
      and protein contents in these samples. No correlation could be established
      between evolution time of the retinal detachment and TBARS content in SF. TBARS
      in SF increases with increasing age in nonmyopic patients. In the samples of
      myopic patients the correlation was established between TBARS content and degree
      of myopia. The group of patients with more than 10 dioptres show a significant
      higher TBARS concentration in SF than any of the other groups studied. It can be
      concluded that lipid peroxidation products in SF originate, at least partially,
      from rod outer segments, and that lipid peroxidation is a process that might play
      a role in the pathogenesis of retinal detachment, specially in myopic patients.

PMID- 8743977
TI  - Inhibition of anthracycline semiquinone formation by ICRF-187 (dexrazoxane) in
      cells.
AB  - The formation of semiquinone free radicals of doxorubicin, epirubicin,
      daunorubicin, and idarubicin was measured by electron paramagnetic resonance
      (EPR) spectroscopy in hypoxic suspensions of chinese hamster ovary (CHO) cells.
      The amount of semiquinone produced was in the order idarubicin >> doxorubicin >
      daunorubicin > epirubicin. The idarubicin semiquinone signal was both the fastest
      to be formed and to decay. Idarubicin, which was the most lipophilic of the
      anthracyclines studied, also displayed the fastest fluorescence-measured cellular
      uptake of drug. Thus, it was concluded that semiquinone formation was dependent
      upon the rate of cellular uptake. Lysed cell suspensions were also shown to be
      capable of producing the doxorubicin semiquinone in the presence of added NADPH.
      The cardioprotective agent dexrazoxane (ICRF-187) was observed to decrease the
      amount of doxorubicin semiquinone observed in cell suspensions. Dexrazoxane also
      decreased the amount of doxorubicin semiquinone observed in the NADPH-lysed cell
      suspension mixture. Neither bipyridine nor deferoxamine decreased NADPH-dependent
      doxorubicin semiquinone formation. These results suggest that dexrazoxane does
      not decrease doxorubicin semiquinone formation through an iron complex formed
      from hydrolyzed dexrazoxane. Dexrazoxane may be inhibiting an NADPH-dependent
      enzyme.

PMID- 8743978
TI  - The oxidizing agent menadione induces an increase in the intracellular molecular
      oxygen concentration in K562 and A431 cells: direct measurement using the new
      paramagnetic EPR probe fusinite.
AB  - The intracellular molecular oxygen concentration in control and menadione-treated
      K562 (an erythroleukemic cell line that grows in suspension) and A431 (an
      epidermal carcinoma that grows in monolayer) cells was measured directly by using
      the new electron paramagnetic resonance (EPR) probe fusinite. Because the
      oxidizing agent menadione is known to damage mitochondria and the cytoplasmic
      membrane in other cell systems, before conducting measurements of oxygen
      concentration in K562 and A431 cells, it was necessary to establish injury in
      these systems as well. Consequently, morphological and flow cytometric analyses
      were conducted after menadione treatment. The data presented here show that the
      two cell lines are heavily damaged by menadione. Once this menadione-induced
      injury was demonstrated, measurements of oxygen concentration were carried out in
      both K562 and A431 cells. Treatment with this quinone induces a sharp increase in
      intracytoplasmic molecular oxygen in both cell lines (from about 1% to about 10
      and 15% in K562 and A431 cells, respectively). In addition, to gain a more
      complete understanding of the effects of menadione on cells, the extracellular
      molecular oxygen concentration and the oxygen consumption rate were also measured
      in control and menadione-treated K562 cells. These measurements demonstrate that
      menadione treatment results in an increase in the extracellular oxygen
      concentration (from about 5% in controls to 15% in treated cells) as well as a
      decrease in the oxygen consumption rate (from about 10 ng O/min/10(6) cells in
      controls to 3 ng O/min/10(6) cells after menadione exposure). The importance of
      the new EPR probe fusinite in monitoring directly cellular functions in which
      oxygen is involved and the effects of menadione on cellular oxygen balance are
      discussed.

PMID- 8743979
TI  - Antioxidants in peripheral nerve.
AB  - Oxidative stress and antioxidants have been related in a wide variety of ways
      with nervous tissue. This review attempts to gather the most relevant information
      related to a) the antioxidant status in non pathologic nervous tissue; b) the
      hypothesis and evidence for oxidative stress (considered as the disequilibrium
      between prooxidants and antioxidants in the cell) as the responsible mechanism of
      diverse neurological diseases; and c) the correlation between antioxidant
      alterations and neural function, in different experimental neuropathies.
      Decreased antioxidant availability has been observed in different neurological
      disorders in the central nervous system, for example, Parkinson's disease,
      Alzheimer's disease, epilepsy, amyotrophic lateral sclerosis, cerebral ischaemia,
      etc. Moreover, the experimental manipulation of the antioxidant defense has led
      in some cases to interesting experimental models in which electrophysiological
      alterations are associated with the metabolic modifications induced. In view of
      the electrophysiological and biochemical effects of some protein kinase C
      inhibitors on different neural experimental models, special attention is
      dedicated to the role of this kinase in peripheral nervous tissue. The nervous
      tissue, central as well as peripheral, has two main special features that are
      certainly related to its antioxidant metabolism: the lipid-enriched membrane and
      myelin sheaths, and cellular excitability. The former explains the importance of
      the glutathione (GSH)-conjugating activity towards 4-hydroxy-nonenal, a
      biologically active product of lipid peroxidation, present in nervous tissue and
      in charge of its inactivation. The impairment of the latter by oxidative damage
      or experimental manipulation of antioxidant metabolism is discussed. Work on
      different experimental neuropathies from author's laboratory has been primarily
      used to provide information about the involvement of free radical damage and
      antioxidants in peripheral nerve metabolic and functional impairment.

PMID- 8743980
TI  - Structure-antioxidant activity relationships of flavonoids and phenolic acids.
AB  - The recent explosion of interest in the bioactivity of the flavonoids of higher
      plants is due, at least in part, to the potential health benefits of these
      polyphenolic components of major dietary constituents. This review article
      discusses the biological properties of the flavonoids and focuses on the
      relationship between their antioxidant activity, as hydrogen donating free
      radical scavengers, and their chemical structures. This culminates in a proposed
      hierarchy of antioxidant activity in the aqueous phase. The cumulative findings
      concerning structure-antioxidant activity relationships in the lipophilic phase
      derive from studies on fatty acids, liposomes, and low-density lipoproteins; the
      factors underlying the influence of the different classes of polyphenols in
      enhancing their resistance to oxidation are discussed and support the contention
      that the partition coefficients of the flavonoids as well as their rates of
      reaction with the relevant radicals define the antioxidant activities in the
      lipophilic phase.

PMID- 8743981
TI  - Extracellular superoxide dismutase in vessels and airways of humans and baboons.
AB  - Extracellular superoxide dismutase (EC SOD) is generally the least abundant SOD
      isozyme in tissues, while the intracellular Cu,Zn SOD is usually the most
      abundant isozyme. The biological significance of EC SOD is unknown.
      Immunolocalization studies show that EC SOD is in the connective tissue
      surrounding smooth muscle in vessels and airways within the lung. Endothelium
      derived relaxing factor, thought to be a nitric oxide (NO) species, is a primary
      mediator of vascular relaxation. During NO.'s diffusion between the endothelium
      and smooth muscle, extracellular superoxide would be the most efficient scavenger
      of NO(.). High levels of extracellular superoxide dismutase in vessels could,
      therefore, be essential to enable NO. to modulate vascular tone. To evaluate the
      hypothesis that vessel walls are functionally rich in extracellular superoxide
      scavenging capacity, this study quantitates the EC SOD levels in pulmonary and
      systemic vessels and in airways. Both pulmonary and systemic arteries in humans
      and baboons were found to contain high activities of EC SOD. The level of EC SOD
      in all human and baboon arteries examined is greater than or equal to the level
      of intracellular Cu,Zn SOD, and EC SOD accounted for over 70% of the total SOD
      activity in some vessels examined. Immunolocalization of EC SOD in human and
      baboon vessels show similar distributions of this enzyme in pulmonary and
      systemic vessels. EC SOD is located beneath the endothelium, surrounding smooth
      muscle cells, and throughout the adventitia of vessels. The high level of EC SOD
      in vessels, and its localization between endothelial and smooth muscle cells,
      suggest that regulation of superoxide may be particularly important in this
      region, possibly in regulating vascular tone.

PMID- 8743982
TI  - The effect of rebamipide on gastric xanthine oxidase activity and type conversion
      in ethanol-treated rats.
AB  - Rebamipide, a novel antipeptic ulcer drug, 2-(4-chlorobenzoylamino)-3-[2(1H)
      quinolinone-4-yl]-propionic acid, was studied for its inhibitory effect on
      gastric xanthine oxidase activity and type conversion of the enzyme that has a
      profound role in free radical generation. Intraperitoneal administration of
      rebamipide at 60 mg/kg body weight reduced gastric mucosal hemorrhagic lesions
      and lipid peroxidation, which was proportional to the inhibitory effect of
      rebamipide on alcohol-induced xanthine oxidase-type conversion and enzyme
      activity. It was also observed that the activity of xanthine oxidase was
      significantly inhibited by administration of rebamipide at 60 mg/kg body weight,
      leading to a significant reduction of lipid peroxide content in alcohol-treated
      rats. The results suggest that alcohol-induced gastric mucosal lesions might be,
      in part, due to the increased activity of xanthine oxidase and type conversion
      rate of the enzyme and the protective effect of rebamipide on gastric mucosal
      lesions would result from its ability to protect against oxidative stress on
      gastric mucosal lesions of alcohol-treated rats.

PMID- 8743983
TI  - Regional lipid peroxidation and protein oxidation in rat brain after hyperbaric
      oxygen exposure.
AB  - Reactive oxygen species may participate in development of neurological toxicity
      resulting from hyperbaric oxygen exposure. To explore the possibility that
      increased reactive O2 metabolite generation may result in oxidative modification
      of lipids and proteins, rats were exposed to five atmospheres (gauge pressure) of
      O2 until development of an electroencephalographic seizure. Lipid peroxidation
      (as thiobarbituric acid-reactive substances) and protein oxidation (as 2,4
      dinitrophenyl-hydrazones) were measured in five brain regions. Oxidized and
      reduced glutathione were also determined because of their role in regulating
      lipid peroxidation. Lipid peroxidation was confined to the frontal cortex and
      hippocampus, while protein oxidation (in both cytoplasmic and membranous
      fractions) and increased oxidized glutathione was evident throughout the brain.
      These results support a role for formation of reactive O2 metabolites from
      hyperbaric O2 exposure and suggest that protein oxidation, especially in soluble
      proteins, may be one of the most sensitive measures.

PMID- 8743984
TI  - 5-Hydroxymethyluracil excretion, plasma TBARS and plasma antioxidant vitamins in
      adriamycin-treated patients.
AB  - The thymine oxidative lesion-5-hydroxymethyluracil (HMUra)-was measured in urine
      collected from cancer patients. These patients all received chemotherapy using
      Adriamycin. Adriamycin (ADR) intercalates DNA coils and interferes with normal
      cell metabolism through diverse biochemical mechanisms that may explain its
      different actions. The anticancer action of ADR could derive from its interaction
      with topoisomerase II, resulting in DNA nicking followed by DNA fragmentation and
      apoptosis. Side effects of ADR-mainly its cardiotoxicity-may derive from the fact
      that ADR generates superoxide and hydroxyl radicals in two ways: redox-cycling
      and a Haber-Weiss type reaction due to Fe-ADR complexes. The oxygen free
      radicals, particularly .OH, are thought to be produced by ADR directly in genomic
      material and attack all its components. 5-Hydroxymethyluracil is a thymine lesion
      provoked by these attacks, and it has been proposed as a marker of DNA
      alterations. In this article, we report the results of a study involving 14
      cancer patients treated with ADR. We found that urine HMUra is significantly
      increased by the anticancer therapy (HMUra (nmol/24 h): 74.4 9.46 vs. 96.3 8.74;
      p < .01), this increase reveals a higher risk of mutagenesis. Our study is the
      first to show an in vivo alteration of DNA by ADR. Results also show that
      thiobarbituric acid reactants increase significantly, and that the vitamin levels
      for retinol and alpha-tocopherol, which are antioxidant vitamins, are lower at
      the end of chemotherapy. We suggest to supplement these patients with vitamins A
      and E, and selenium to reduce the side effects of ADR.

PMID- 8743985
TI  - Hemoglobin: a mechanism for the generation of hydroxyl radicals.
AB  - Oxyhemoglobin (HbO2) reduces Fe(III)NTA aerobically to become methemoglobin
      (metHb) and Fe(II)NTA. These conditions are favorable for the generation via
      Fenton chemistry of the hydroxyl radical that was measured by HPLC using
      salicylate as a probe. The levels of hydroxyl radicals generated are a function
      of both the percent metHb formed and the chemical nature of the buffer. The rates
      of formation of both metHb and hydroxyl radicals were dependent upon the
      concentration of Fe(III)NTA. Of the buffers tested, HEPES was the most effective
      scavenger of hydroxyl radicals while the other buffers scavenged in the order:
      HEPES > Tris > MPOS > > NaCL approximately unbuffered. The addition of catalase
      to remove H2O2 or bathophenanthroline to chelate Fe(II) inhibited virtually all
      hydroxyl radical formation. Carbonyl formation from free radical oxidation of
      amino acids was found to be 0.1 mol/mol of hemoglobin. These experiments
      demonstrate the ability of hemoglobin to participate directly in the generation
      of hydroxyl radicals mediated by redox metals, and provide insight into potential
      oxidative damage from metals released into the blood during some pathologic
      disorders including iron overload.

PMID- 8743986
TI  - Genetic and physical mapping of the progressive epilepsy with mental retardation
      (EPMR) locus on chromosome 8p.
AB  - Progressive epilepsy with mental retardation (EPMR) is an autosomal recessive
      disorder discovered recently from an isolated region in Finland. The disorder is
      characterized by normal early development, generalized tonic-clonic seizures with
      onset at 5-10 years of age, and progressive mental retardation beginning 2-5
      years after the onset of seizures. We recently mapped the EPMR locus to a 7-cM
      region on chromosome 8p between markers AFM185xb2 and D8S262. A recombination
      detected with a new microsatellite marker AFMa054td9 narrows the region to 4 cM.
      A yeast artificial chromosome (YAC) contig containing 22 YACs was constructed
      across the disease gene region. The YAC contig is characterized by a collection
      of 19 YAC-end sequence-tag sites together with seven microsatellite markers. The
      entire YAC contig spans a minimum of 3 Mb. Moreover, the distal end of the contig
      contains a subtelomeric YAC yRM2205 that anchors the contig to the telomere.
      Construction of a YAC contig across the disease gene region is an essential step
      toward the isolation of the EPMR gene.

PMID- 8743987
TI  - The characterization and localization of the mouse thymopoietin/lamina-associated
      polypeptide 2 gene and its alternatively spliced products.
AB  - Thymopoietins (Tmpos) are a group of ubiquitously expressed nuclear proteins,
      with sequence homology to lamina-associated polypeptide 2 (LAP2). Here we report
      the isolation and characterization of seven mouse Tmpo mRNA transcripts named
      Tmpo alpha, beta, beta', gamma, epsilon, delta, and zeta. The alpha, beta, and
      gamma Tmpo cDNA clones are the mouse homologs of the previously characterized
      human alpha, beta, and gamma TMPOs, respectively, whereas Tmpo epsilon, delta,
      and zeta are novel cDNAs. Additionally, the mouse Tmpo gene was cloned and
      characterized. It is a single-copy gene organized in 10 exons spanning
      approximately 22 kb, which encodes all of the described Tmpo cDNA sequences,
      located in the central region of mouse chromosome 10. The almost identical
      genomic organization between the human and mouse genes, and the novel
      alternatively spliced mouse transcripts, led us to reanalyze the human TMPO gene.
      The human beta-specific domain was found to be encoded by 3 exons designated 6a,
      6b, and 6c and not by a single exon as described previously. These findings
      suggest that there may be more human transcripts than currently recognized. The
      possible involvement of the new growing family of Tmpo proteins in nuclear
      architecture and cell cycle control is discussed.

PMID- 8743988
TI  - A comprehensive map of the porcine genome.
AB  - We report the highest density genetic linkage map for a livestock species
      produced to date. Three published maps for Sus scrofa were merged by genotyping
      virtually every publicly available microsatellite across a single reference
      population to yield 1042 linked loci, 536 of which are novel assignments,
      spanning 2286.2 cM (average interval 2.23 cM) in 19 linkage groups (18 autosomal
      and X chromosomes, n = 19). Linkage groups were constructed de novo and mapped by
      locus content to avoid propagation of errors in older genotypes. The physical and
      genetic maps were integrated with 123 informative loci assigned previously by
      fluorescence in situ hybridization (FISH). Fourteen linkage groups span the
      entire length of each chromosome. Coverage of chromosomes 11, 12, 15, and 18 will
      be evaluated as more markers are physically assigned. Marker-deficient regions
      were identified only on 11q1.7-qter and 14 cen-q1.2. Recombination rates (cM/Mbp)
      varied between and within chromosomes. Short chromosomal arms recombined at
      higher rates than long arms, and recombination was more frequent in telomeric
      regions than in pericentric regions. The high-resolution comprehensive map has
      the marker density needed to identify quantitative trait loci (QTL), implement
      marker-assisted selection or introgression and YAC contig construction or
      chromosomal microdissection.

PMID- 8743989
TI  - An accurate method for comparing transcript levels of two alleles or highly
      homologous genes: application to fibrillin transcripts in Marfan patients'
      fibroblasts.
AB  - We introduce here a novel and generally applicable, solid-phase minisequencing
      based approach for rapid estimation of relative levels of transcripts with high
      sequence homology. This study was undertaken to screen for the consequences of
      different fibrillin-1 mutations on the transcript levels in patients with the
      Marfan syndrome (MFS). This dominantly inherited, connective tissue disorder is
      characterized by pleiotrophic symptoms in cardiovascular, skeletal, and ocular
      systems. A spectrum of disease mutations in the gene encoding fibrillin-1 (FBN1),
      a glycoprotein component of extracellular matrix microfibrils, has been
      identified in MFS patients, but the mechanisms by which mutations result in
      different phenotypic manifestations are still unknown to a large extent. Our data
      from the quantitation of FBN1 transcripts provide support for the hypothesis that
      mutations causing premature stop codons result in a milder phenotype than
      classical MFS by reducing the stability of the mutant transcript and,
      consequently, decreasing the interference of mutant polypeptide in the formation
      of fibrillin fibers. We also applied this mRNA quantitation method to determine
      the relative ratio between transcripts from the genes coding for two highly
      homologous microfibrillar components, FBN1 and FBN2, in control fibroblast
      cultures as well as in fibroblasts from MFS patients. Interestingly, these data
      show large variations between the levels of the two transcripts in fibroblast
      cultures, but these variations do not correlate either with the nature of the
      disease mutation or to the clinical MFS phenotype.

PMID- 8743990
TI  - Genomic organization of TEL: the human ETS-variant gene 6.
AB  - We have constructed a detailed map of the genomic region containing the ETS
      variant gene 6 (ETV6), involved in translocations and deletions associated with
      hematologic malignancies. Thirty-eight cosmids were characterized belonging to
      two contigs spanning 340 kb, and an EcoRl restriction map was developed. The gap
      between the two contigs, 2 kb in size, was closed by PCR. The contigs contain the
      complete coding sequence and the 5' and 3' UTRs of ETV6. Eight exons accounting
      for the ETV6 cDNA sequence were identified. The helix-loop-helix (HLH) motif is
      coded by exons 3 and 4, whereas exons 6-8 code for the ETS DNA-binding domain.
      All introns show consensus 5' donor and 3' acceptor splice sites. Introns 1 and 2
      span 100 and 82 kb, respectively, and introns 3-7 range from 15 to 1.3 kb. An
      alternative exon 1 (exon 1B) is localized in intron 2. The 5' end of the ETV6
      gene is associated with a CpG island characterized by the presence of four Notl,
      four Sacll, and three BssHll recognition sites and several SP1- and AP2-binding
      motifs. Alternative polyadenylation at the 3' end of the ETV6 gene generates the
      three transcripts of 6200, 4300, and 2400 nucleotides, respectively. The ETV6
      gene spans 240 kb and is flanked at its 5' and 3' end by D12S1697 and D12S98,
      respectively. The markers D12S1095 and D12S89 are located in the first intron.
      Two new DNA polymorphisms were identified in the ETV6 gene, which will be useful
      for the analysis of loss of heterozygosity reported for the ETV6 gene in
      leukemia.

PMID- 8743992
TI  - Mapping of the OB receptor to 1p in a region of nonconserved gene order from
      mouse and rat to human.
AB  - As part of an effort to identify informative molecular markers for genetic
      analysis of human pedigrees segregating for obesity, we have developed a genetic
      map of human 1p in the region of the OB receptor (OBR), the gene that is
      defective in murine diabetes (Obrdb) and rat Zucker fatty (Obrfa) mutations
      located on mid-chromosome 4 and chromosome 5, respectively. OBR was mapped 0.9 cR
      centromeric to WI-9515 and 2.2 cR telomeric of WI-7249 by radiation hybrid (RH)
      mapping. Ten yeast artificial chromosomes (YACs) containing OBR were identified,
      confirming the location of OBR centromeric to WI-9515 and telomeric to WI-7249.
      Additionally, five P1 artificial chromosomes (PACs) were identified that
      comprised a contiguous series of overlapping clones spanning the length of OBR.
      WI-5182 was contained within the two PACs that are 3' of OBR. Using a panel of 68
      individuals from a single three-generation family and an additional nuclear
      family, we have mapped 18 polymorphic markers including phosphoglucomutase 1
      (PGM1), which is centromeric to Obrdb / Obrfa, and D1S85, which is telomeric to
      Obrdb / Obrfa in the mouse and rat. The following composite map integrates these
      radiation hybrid, genetic, and physical maps: Centromere-@WI-7249-[OBR; WI-5182]
      D1S198-[WI-9515; WI-6550; D1S2866]-D1S2825-[WI-3077; D1S2886]-[D1S515; DS1613;
      PGM1]-[D1S312; D1S473; D1S230; D1S246; D1S203]-D2S1643-[D1S1669; D1S1596;]UNCJ
      D1S476- D1S85-D1S220-C8B-GTAT1A7. Unresolvable markers are within brackets. A
      comparison of gene order on mouse chromosome 4, rat chromosome 5, and human 1p
      indicates that between rodents and humans, there has been a rearrangement of the
      gene order in the region surrounding OBR.

PMID- 8743991
TI  - A P1-based physical map of the Drosophila euchromatic genome.
AB  - A PCR-based sequence-tagged site (STS) content mapping strategy has been used to
      generate a physical map with 90% coverage of the 120-Mb euchromatic portion of
      the Drosophila genome. To facilitate map completion, the bulk of the STS markers
      was chosen in a nonrandom fashion. To ensure that all contigs were localized in
      relation to each other and the genome, these contig-building procedures were
      performed in conjunction with a large-scale in situ hybridization analysis of
      randomly selected clones from a Drosophila genomic library that had been
      generated in a P1 cloning vector. To date, the map consists of 649 contigs with
      an STS localized on average every 50 kb. This is the first whole genome that has
      been mapped based on a library constructed with large inserts in a vector that is
      maintained in Escherichia coli as a single-copy plasmid.

PMID- 8743993
TI  - Identification and characterization of a new gene physically linked to the ATM
      gene.
AB  - Ataxia telangiectasia (AT) is an autosomal recessive disease of unknown etiology
      associated with cerebellar ataxia, oculocutaneous telangiectasia,
      immunodeficiency, and hypersensitivity to ionizing radiation. Although AT has
      been divided into four complementation groups by its radioresistant-DNA synthesis
      phenotype, the ATM gene has been isolated as the candidate gene responsible for
      all AT groups. We identified a new gene, designated NPAT, from the major AT locus
      on human chromosome 11q22-q23. The gene encoded a 1421-amino-acid protein
      containing nuclear localization signals and phosphorylation target sites by
      cyclin-dependent protein kinases associated with E2F. The messenger RNA of NPAT
      was detected in all human tissues examined, and its genomic sequence was strongly
      conserved through eukaryotes, suggesting that the NPAT gene may be essential for
      cell maintenance and may be a member of the housekeeping genes. Analysis of the
      genomic region of NPAT surprisingly revealed that the gene existed only 0.5 kb
      apart from the 5' end of the ATM transcript with opposite transcriptional
      direction. It may be possible to propose the idea that the promoter region could
      be shared by both housekeeping genes and that each gene could influence the
      expression of the other.

PMID- 8743994
TI  - A new approach using multiplex long accurate PCR and yeast artificial chromosomes
      for bacterial chromosome mapping and sequencing.
AB  - An efficient approach for structural studies on bacterial chromosomes is
      presented. It is based on high-resolution PCR map construction by using a
      multiplex long accurate PCR (MLA PCR) protocol and a YAC clone carrying the
      region to be mapped as indicator. The high-resolution PCR map of the bacillus
      subtilis rrnB-dnaB region is presented as an example. Data are also presented on
      the use of DNA generated by LA PCR for sequencing; they are relevant to LA PCR
      induced mutations and justify the application of such mapping for sequencing long
      stretches of bacterial chromosomes.

PMID- 8743995
TI  - BCM Search Launcher--an integrated interface to molecular biology data base
      search and analysis services available on the World Wide Web.
AB  - The BCM Search Launcher is an integrated set of World Wide Web (WWW) pages that
      organize molecular biology-related search and analysis services available on the
      WWW by function, and provide a single point of entry for related searches. The
      Protein Sequence Search Page, for example, provides a single sequence entry form
      for submitting sequences to WWW servers that offer remote access to a variety of
      different protein sequence search tools, including BLAST, FASTA, Smith-Waterman,
      BEAUTY, PROSITE, and BLOCKS searches. Other Launch pages provide access to (1)
      nucleic acid sequence searches, (2) multiple and pair-wise sequence alignments,
      (3) gene feature searches, (4) protein secondary structure prediction, and (5)
      miscellaneous sequence utilities (e.g., six-frame translation). The BCM Search
      Launcher also provides a mechanism to extend the utility of other WWW services by
      adding supplementary hypertext links to results returned by remote servers. For
      example, links to the NCBI's Entrez data base and to the Sequence Retrieval
      System (SRS) are added to search results returned by the NCBI's WWW BLAST server.
      These links provide easy access to auxiliary information, such as Medline
      abstracts, that can be extremely helpful when analyzing BLAST data base hits. For
      new or infrequent users of sequence data base search tools, we have preset the
      default search parameters to provide the most informative first-pass sequence
      analysis possible. We have also developed a batch client interface for Unix and
      Macintosh computers that allows multiple input sequences to be searched
      automatically as a background task, with the results returned as individual HTML
      documents directly to the user's system. The BCM Search Launcher and batch client
      are available on the WWW at URL http:@gc.bcm.tmc.edu:8088/search-launcher.html.

PMID- 8743996
TI  - Multidrug resistance gene expression in childhood medulloblastoma: correlation
      with clinical outcome and DNA ploidy in 29 patients.
AB  - Twenty-nine children treated for medulloblastoma between 1987 and 1991 were
      reviewed. Thirteen patients with high-risk medulloblastoma characterized by
      incomplete resection, diploid tumor or subarachnoid dissemination received
      chemotherapy following radiation therapy. Three received postoperative
      chemotherapy. Eight patients who had been treated with postoperative radiation
      therapy also received chemotherapy for recurrent tumors. After a minimum 3-year
      follow-up period, 16 were alive but 13 had died from recurrent tumors. In order
      to evaluate the possible participation of P-glycoprotein (Pgp)-mediated multidrug
      resistance (MDR) in medulloblastoma therapy and its correlation with prognosis,
      archival specimens were examined by immuno-histochemistry utilizing 3 monoclonal
      antibodies against Pgp and 6 cases by reverse-transcriptase polymerase chain
      reaction (RT-PCR) using MDR1-specific primers. Sixteen patients (55%) had MDR
      expression detected either by 1 of the 3 antibodies or by RT-PCR. DNA ploidy
      study was also performed on 18 specimens. We correlated patients' outcome with
      variable factors (extent of surgical resection, chemotherapy, DNA ploidy) and MDR
      expression. Patients who were treated with radiation therapy and adjuvant
      chemotherapy had a significantly better (p = 0.036) survival than those with
      radiation therapy alone, despite the fact that the former group of patients was
      considered to be high-risk. The extent of surgical resection and DNA ploidy did
      not correlate with prognosis. However, a statistically significant association
      was found between MDR expression and outcome (p = 0.007). Among the patients who
      received chemotherapy, positive MDR expression significantly correlated with poor
      outcome (p = 0.036). Our results showed that Pgp-mediated intrinsic MDR in
      medulloblastomas seems to correlate with an adverse outcome. This information may
      be used in designing new therapeutic protocols for medulloblastoma.

PMID- 8743997
TI  - Prognostic value of contrast-enhanced magnetic resonance imaging in brainstem
      gliomas.
AB  - Brainstem gliomas are an important oncologic problem in the pediatric age group,
      constituting between 10 and 15% of childhood central nervous system neoplasms. A
      new classification scheme based on magnetic resonance imaging (MRI) has recently
      been proposed leading to speculation that gadolinium-DTPA-enhanced MRI may prove
      useful in defining the prognosis of subsets of patients with these tumors. We
      retrospectively reviewed gadolinium-DTPA-enhanced MRIs in 26 consecutive newly
      diagnosed pediatric patients (11 males, 15 females) from our institution between
      June 1988 and June 1994 with the diagnosis of diffuse brainstem glioma. The site,
      extent of invasion, T1 and T2 signals, and the pattern and the degree of contrast
      enhancement of the tumors were evaluated. We correlated the image features,
      clinical symptoms, and survival period in each patient. Seventeen tumors
      demonstrated contrast enhancement and 9 did not. The survival in the whole group
      ranged between 3 months and > 5 years with a median of 9 months. There was no
      statistical difference in the median survival between patients with or without
      contrast enhancement (11 versus 8 months).

PMID- 8743998
TI  - Delayed and progressive brain injury in children and adolescents with head
      trauma.
AB  - We performed serial CT scans on 351 children and adolescents with serious closed
      head injury. Delayed or progressive lesions were encountered in 145 (41%). The
      occurrence of such delayed cerebral injuries correlated with the severity of the
      initial head trauma, with the presence of major extracranial injury and with
      studies of coagulopathy on admission. The presence of delayed cerebral injury had
      a profound influence on survival and recovery from head trauma, especially when
      the initial severity of the head injury was taken into account. We conclude that
      serial CT scans provide a reliable means of diagnosing and following the progress
      of delayed cerebral injury in the pediatric population.

PMID- 8743999
TI  - Role of apnea in nonaccidental head injury.
AB  - We hypothesize that apnea induced by shaking or by shaking combined with impact
      plays a major role in the pathophysiology of nonaccidental head trauma and
      accounts for the poor outcome in this subgroup of patients. In a retrospective
      study of 28 children who suffered significant nonaccidental head injury, 57% had
      a history of apnea prior to hospitalization, 82% were intubated upon admission,
      and 71% had early seizures. For further evidence of ischemia and hypoxia, the
      first recorded blood pressure was < 80 in 50% and the arterial pH < 7.3 in 54%.
      Seventy-one percent had diffuse brain swelling which is characteristic of
      cerebral hypoxia and/or ischemia on the first CT scan. None of the children who
      had clinical evidence of cerebral hypoxia or ischemia had a good outcome. We
      conclude that trauma-induced apnea causes cerebral hypoxia and/or ischemia which
      is more fundamental to outcome than the mechanism of injury (shaken vs. shaken
      with impact), subdural hemorrhage, subarachnoid hemorrhage, diffuse axonal
      injury, parenchymal shear, or brain contusion.

PMID- 8744000
TI  - Hereditary factors in the etiology of neural tube defects. Results of a survey.
AB  - Ongoing research in the etiology of neural tube defects is increasingly being
      directed towards the molecular mechanisms at work in the formation of these
      complex lesions. We undertook to review the family history of patients in a large
      myelomeningocele/spina bifida clinic in an effort to identify genetic trends in
      these families, particularly as they relate to current research efforts and
      laboratory models. Surveys were received from 363 patients (35.5% of the clinic
      population) and analyzed. The myelomeningocele recurrence rate was 4.3%. Seven
      sets of twins were identified and all were discordant for their spinal lesions. A
      family history of spina was found to be evenly distributed between maternal and
      paternal relatives, rather than tending to follow through the maternal side.
      Epilepsy was more commonly found on the maternal side of the family, most likely
      reflecting the postulated causal relationship between maternal anticonvulsant use
      and the occurrence of spina bifida, although also possibly supporting the concept
      that a genetic predisposition for maternal epilepsy may also be associated with a
      higher frequency of birth defects among children of epileptics, independent of
      anticonvulsant use. Patients with spina bifida in the setting of Waardenburg
      syndrome and fragile X syndrome were also identified and will be discussed.

PMID- 8744001
TI  - Cervical meningoceles and myelocystoceles: a unifying hypothesis.
AB  - The classification and embryogenesis of cystic cervical dysraphic lesions are
      discussed in the light of the authors' experience and review of the literature.
      It is felt that these lesions are best described as meningoceles or
      myelocystoceles, and the use of the term 'myelomeningocele' may be more confusing
      than clarifying. The authors hypothesize that the cervical meningocele and the
      myelocystocele are part of a spectrum of the same underlying developmental
      abnormality, namely limited dorsal myeloschisis, with the eventual abnormality
      depending on the presence or absence of associated hydromyelia.

PMID- 8744002
TI  - Bone regrowth and recurrence of symptoms following decompression in the infant
      with Chiari II malformation.
AB  - The Chiari malformation is the leading cause of death in infants with
      myelodysplasia. While controversial, early operative decompression may halt or
      reverse the progression of symptoms. If symptoms recur after initial improvement,
      attention is directed to assuring shunt patency and the absence of hydromyelia
      and not to reassessment of the area of bone decompression. Three infants are
      presented who initially improved after Chiari decompression only to have
      recurrence of symptoms several months after surgery. In each case, regrowth of
      bone at the site of previous decompression was documented radiographically and at
      surgery. In one case, regrowth of bone occurred twice. Each child stabilized or
      improved following further decompressive surgery. A theory of bone regrowth and a
      possible means of prevention are discussed. If recurrence of Chiari symptoms
      occurs after decompressive surgery in infants, thin section CT with bone windows
      through the operative site should be performed to exclude bone regrowth and
      recurrent compression.

PMID- 8744003
TI  - Suprasellar tuberculoma causing endocrinologic disorders and imitating
      craniopharyngioma.
AB  - A patient is reported with a suprasellar tuberculoma which imitated a
      craniopharyngioma on computed tomography scan and magnetic resonance imaging of
      the brain. This lesion developed during irregularly used antituberculous therapy
      and caused endocrinologic disorders 3 years after the original diagnosis of
      tuberculous meningitis. Surgery was performed to confirm the diagnosis and also
      to decompress the optic pathways. Five months later, the lesion disappeared
      completely after appropriate antituberculous treatment.

PMID- 8744004
TI  - Dynamic MRI sensitized to cerebral blood oxygenation and flow during sustained
      activation of human visual cortex.
AB  - Changes in cerebral blood oxygenation and flow during prolonged activation of
      human visual cortex (6-min video projection) were monitored using high-resolution
      T2*- and T1-weighted gradient-echo MRI in identical sessions. Oxygenation
      sensitive recordings displayed an initial signal increase (oxygenation
      "overshoot"), a subsequent signal decrease extending over 4-5 min (relative
      deoxygenation), and a signal drop after the end of stimulation that mirrored the
      initial response (oxygenation "undershoot"). Flow-sensitive MRI demonstrated that
      the inflow effect remained elevated during the entire period of stimulation. The
      observation of gradually decreasing cerebral blood oxygenation, despite
      persisting elevation of blood flow, may be understood to be an accumulation of
      deoxyhemoglobin due to the progressive up-regulation of oxidative
      phosphorylation. The present findings support a concept in which transitions
      between functional states lead to an uncoupling of perfusion (oxygen delivery)
      from oxidative metabolism (oxygen consumption) whereas steady-state activity
      achieves their recoupling.

PMID- 8744005
TI  - Microbubbles as novel pressure-sensitive MR contrast agents.
AB  - Magnetic resonance imaging contrast agents that are sensitive to pressure would
      be useful for evaluating cardiovascular function. One such potential contrast
      agent consists of gas-filled liposome microbubbles. The magnetic susceptibility
      of the microbubbles locally perturb the static magnetic field, which influences
      the transverse-relaxation properties of the surrounding medium. Changes in the
      pressure alter the bubble dimensions, which affects the magnetic field
      perturbations and, hence, the transverse-relaxation. The effect of these
      microbubbles on the T2 relaxation times of a water-based medium was measured for
      liposomes filled with different gases-nitrogen, argon, air, oxygen, xenon, neon,
      perfluoropentane, perfluorobutane, and sulfur hexafluoride. The air-filled,
      perfluoropentane-filled and the oxygen-filled liposomes demonstrated the largest
      effect on transverse-relaxation. The influence of pressure on both gradient-echo
      and spin-echo signal intensities for air-filled microbubbles was also evaluated.
      Pressure-induced changes in signal intensity were consistently observed for both
      the spin-echo and gradient-echo pulses sequences.

PMID- 8744006
TI  - Detecting cortical activities from fMRI time-course data using the MUSIC
      algorithm with forward and backward covariance averaging.
AB  - A method is proposed for processing time-course fMRI data taken with successive
      single-shot echo-planar imaging. The proposed method uses a two-dimensional
      version of the multiple signal classification (MUSIC) algorithm and the technique
      called covariance averaging, both of which were developed in the field of sensor
      array processing. The proposed method consists of four steps: calculate the
      averaged data covariance matrix, determine the number of activities using this
      covariance matrix, estimate the locations of the activities, and estimate their
      time evolution curves. Computer simulation results showed that a nearly fourfold
      improvement in the spatial resolution can be attained due to the method's super
      resolution capability.

PMID- 8744007
TI  - Pencil excitation with interleaved fourier velocity encoding: NMR measurement of
      aortic distensibility.
AB  - A technique is presented for rapidly and noninvasively determining aortic
      distensibility, by NMR measurement of pulse-wave velocity in the aorta. A
      cylinder of magnetization is excited along the aorta, with Fourier-velocity
      encoding and readout gradients applied along the cylinder axis. Cardiac gating
      and data interleaving improve the effective time resolution to as high as 3 ms.
      Wave velocities are determined from the position of the foot of the flow wave in
      the velocity profiles. Evidence of helical flow distal to the aortic arch can be
      seen in normal subjects, while disturbed flow patterns are visible in patients
      with aneurysms and dissections.

PMID- 8744008
TI  - Substrate selection early after reperfusion of ischemic regions in the working
      rabbit heart.
AB  - Several substrates are available in vivo for oxidation by the myocardium.
      Although substrate selection has been studied extensively in normoxic myocardium,
      relatively little is known about substrate preference very early during
      reperfusion after ischemia. Carbon-13 isotopomer analysis was used to study
      substrate usage by nonischemic and reperfused-ischemic myocardium in a working
      heart that was subjected to 15 min or regional ischemia and reperfused for 5 min.
      Compared with nonischemic myocardium, the contribution of acetoacetate to acetyl
      coenzyme A was increased in the reperfused-ischemic region, and the contribution
      of exogenous lactate was decreased. Free fatty acid oxidation, however, was not
      different in the two regions. These results indicate that (1) early during
      reperfusion, ketone body oxidation may be more significant than has been
      emphasized, (2) the relative contribution of fatty acids to acetyl coenzyme A is
      not sensitive to ischemia followed by reperfusion, and (3) Carbon-13 magnetic
      resonance spectroscopy methods may be used for analysis of spatial heterogeneity
      of metabolism in the heart.

PMID- 8744009
TI  - Regional myocardial oxygen tension: 19F MRI of sequestered perfluorocarbon.
AB  - A novel noninvasive method of measuring local myocardial oxygen tension (pO2) in
      the perfused rat heart using 19F MRI is demonstrated. Tissue pO2 was determined
      on the basis of the 19F spin-lattice relaxation rate (R1) of perflubron
      (perfluorooctyl bromide) sequestered in the heart after IV infusion of an
      emulsion. Spectroscopic measurement of R1 was previously used to measure a global
      weighted average of oxygen status. 19F MRI now provides 3D spatial resolution
      indicating local cardiac pO2 under normally perfused, globally ischemic, and
      regionally ischemic conditions.

PMID- 8744010
TI  - Automated feature extraction for the classification of human in vivo 13C NMR
      spectra using statistical pattern recognition and wavelets.
AB  - If magnetic resonance spectroscopy (MRS) is to become a useful tool in clinical
      medicine, it will be necessary to find reliable methods for analyzing and
      classifying MRS data. Automated methods are desirable because they can remove
      user bias and can deal with large amounts of data, allowing the use of all the
      available information. In this study, techniques for automatically extracting
      features for the classification of MRS in vivo data are investigated. Among the
      techniques used were wavelets, principal component analysis, and linear
      discriminant function analysis. These techniques were tested on a set of 75 in
      vivo 13C spectra of human adipose tissue from subjects from three different
      dietary groups (vegan, vegetarian, and omnivore). It was found that it was
      possible to assign automatically 94% of the vegans and omnivores to their correct
      dietary groups, without the need for explicit identification or measurement of
      peaks.

PMID- 8744011
TI  - Simultaneous 3D NMR spectroscopy of fluorine and phosphorus in human liver during
      5-fluorouracil chemotherapy.
AB  - Simultaneous multivoxel 31P and 19F 3D localized NMR spectroscopy is demonstrated
      on a phantom and in the liver of patients undergoing bolus-infusion 5
      fluorouracil chemotherapy. The 19F and 31P spectra were localized with 8 x 8 x 8
      3D chemical-shift imaging, with both nuclei sharing the same field of view and
      voxel size (27 and 64 ml in phantom and liver, respectively) using a 1.5-Tesla
      clinical imager with two RF channels and a dual-tuned surface coil. The
      repetition time (TR = 0.26 s) and Ernst nutation angles (theta E = 32 degrees for
      19F, 28 degrees for 31P) were chosen to optimize the signal-to-noise ratio (SNR)
      per-unit time for the 0.5- to 2-s T1 range of the 19F and 31P metabolites of
      interest. The overall examination time, including tuning, imaging, shimming and
      dual-nuclear spectroscopy, was under 90 min. Simultaneous acquisition of 31P and
      19F spectra will permit the study of the influence of hepatic and/or tumor
      metabolism on the uptake and catabolism of fluoropyrimidine drugs with no extra
      measurement time.

PMID- 8744012
TI  - NMR studies on human, pathologically changed synovial fluids: role of
      hypochlorous acid.
AB  - Recently, it has been reported that hypochlorous acid (HOCl), a special product
      of neutrophil myeloperoxidase, degrades N-acetyl groups of N-acetylglucosamine,
      chondroitin sulfate, hyaluronic acid, and minced articular cartilage via a
      transient product to acetate. This work concerns 1H NMR investigations of
      synovial fluids of patients with rheumatoid arthritis (RA). Synovial fluids of
      patients with severe forms of this disease are characterized by enhanced 1H NMR
      signals for N-acetyl groups (approximately 2.0 ppm) and acetate (1.90 ppm) and
      the appearance of a broad but less intense signal at 2.35 ppm. It is likely that
      this signal corresponds to the transient, chlorinated product of degradation of N
      acetyl groups by hypochlorous acid. Moreover, 1H NMR signal intensities of N
      acetyl groups and acetate strongly correlate with the myeloperoxidase activities
      in synovial fluids from patients with rheumatoid arthritis. These results have
      been confirmed by treatment of native sheep synovial fluid with sodium
      hypochlorite, resulting in the formation of the same resonances as observed in
      pathologically changed synovial fluids from humans. Thus, it is concluded that
      HOCl plays an important role for the cartilage degradation during rheumatoid
      arthritis.

PMID- 8744013
TI  - Improving the temporal resolution of functional MR imaging using keyhole
      techniques.
AB  - Using a keyhole technique, it is shown that the data acquisition rate of gradient
      echo imaging for functional MRI (fMRI) studies can be increased substantially.
      The resulting enhancement of the temporal resolution of fMRIs was accomplished
      without modifying the hardware of a conventional MRI system. High spatial
      resolution fMRI images were first collected with conventional full k-space
      acquisition and image reconstruction. Using the same data set, simulation
      reconstruction using the keyhole principle and zero-padding were performed for
      comparison with the full k-space reconstruction. No significant changes were
      found for fMRI images generated from the keyhole technique with a data sharing
      profile of 50% of the k-space. As k-space data sharing profiles increased to 75
      and 87.5%, the keyhole fMRI images began to show only modest changes in
      activation intensity and area compared with the standard images. In contrast,
      zero-padding fMRI images produced a significant disparity both in activation
      intensity and area relative to the truly high-resolution fMRI images. The keyhole
      technique's ability to retain the intensity and area of fMRI information, while
      substantially reducing acquisition time, makes it a promising method for fMRI
      studies.

PMID- 8744014
TI  - Improved visualization of breast lesions with gadolinium-enhanced magnetization
      transfer MR imaging.
AB  - A pulse sequence with magnetization transfer as the main contrast mechanism (MT
      FLASH) was developed for improved imaging of breast lesions that requires neither
      fat suppression nor postprocessing. After optimization of the sequence in phantom
      and volunteer studies, a clinical pilot study with 14 patients was performed. In
      carcinomas the relative signal increase after Gd-DTPA administration was on
      average 34% in MT-FLASH images compared with 169% in conventional T1-weighted
      (T1W) three-dimensional FLASH images. In MT-FLASH images, all lesions
      demonstrated a signal intensity higher than that of fat; in T1W images, all
      lesions have a lower signal intensity. The average postcontrast carcinoma-to-fat
      contrast-to-noise ratios were +11.6 and -14.2, respectively. The conspicuity of
      12 of 13 carcinomas was improved in postcontrast MT-FLASH imaging enables
      excellent visualization of Gd-DTPA-enhancing breast lesions.

PMID- 8744015
TI  - Multislice interleaved excitation cycles (MUSIC): an efficient gradient-echo
      technique for functional MRI.
AB  - A method providing improved slice efficiency for gradient-echo imaging requiring
      long echo times, such as in functional neuromagnetic resonance imaging, is
      presented. To enhance the volume coverage while maintaining the short imaging
      time of a conventional single-slice gradient-echo technique, an interleaved
      multislice excitation is performed during the echo time. This technique allows
      detection of susceptibility changes, e.g., the acquisition of stimulated human
      cortical activation maps, on clinical MR instruments at multiple planes within
      total imaging times of a few seconds. The efficiency of the technique is
      demonstrated in the detection of temporary changes in T2* in functional MRI
      experiments of the human visual cortex at magnetic field strengths of 2 Tesla and
      3 Tesla. Fourteen 128 x 128 slices can be acquired in 13 s to cover a large
      volume-of-interest in the same time that would be required for single-slice
      acquisition using the conventional technique.

PMID- 8744016
TI  - Optimization of torque-balanced asymmetric head gradient coils.
AB  - Local gradient coils can improve the performance of echo-planar, diffusion, and
      short TE imaging in the brain. A modified singular value decomposition algorithm,
      which allows the rapid optimization and comparison of designs, was employed to
      optimize head size gradient coils. A theoretical expression for the torque on a
      cylindrical coil is presented and used to design coils that are free from torque
      while pulsed within a magnetic field. Gradient coils of various lengths both with
      and without torque constraints were compared; although torque-free coils do not
      perform as well as unbalanced coils, asymmetric torque-balanced coils can achieve
      comparable homogeneity with only a modest increase in inductance and resistance.
      Both types of coils outperform body size gradient coils by a dramatic margin. A
      three-axis head gradient designed using these techniques was constructed and used
      for brain imaging on a clinical scanner.

PMID- 8744017
TI  - Velocity encoding using ghost artifacts.
AB  - Motion artifacts represent a significant limitation of MRI, and an ideal solution
      to that problem has proved elusive. However, in this paper, motion artifacts are
      not considered as the usual enemy and are not suppressed; on the contrary, they
      are deliberately created to encode flow information. In MRI, velocity is encoded
      readily into the phase of a pixel. However, if the pixel contains overlapping
      signals, the phase of one of these signals now has consequences on both the
      magnitude and phase of the resulting pixel. It is shown here that an overlap of
      information may be used to encode velocity both in the phase and in the magnitude
      of an image, making the velocity-encoding process faster. The overlap of
      information is obtained by superposing ghosting artifacts of different orders and
      information is retrieved about complex intensity and velocity in two dimensions
      using the equivalent of two images instead of the usual three images. The price
      to pay to do so is some loss of simplicity in the equations involved, an increase
      in reconstruction computing time requirements, and a factor of 4 decrease in
      signal-to-noise ratio in the velocity measurements.

PMID- 8744018
TI  - Fast interleaved echo-planar imaging with navigator: high resolution anatomic and
      functional images at 4 Tesla.
AB  - Echo-planar imaging (EPI) is sensitive to magnetic field inhomogeneities, which
      lead to signal loss and geometric distortions of the image. Magnetic field
      inhomogeneities induced by susceptibility differences, as encountered in the
      human body, increase with the magnetic field strength, thus, complicating
      implementation of high resolution EPI techniques on high magnetic field systems.
      These problems were overcome by using a fast multishot high resolution EPI method
      that uses variable flip angles, center-out k-space sampling, and navigator
      echoes. This approach maximizes signal-to-noise ratio, reduces flow artifacts,
      and permits correction of intersegment amplitude and phase variations, providing
      high spatial and temporal resolution. This scheme can be implemented with a
      single magnetization preparation for contrast that precedes the segments. The
      utility of this ultrafast segmented EPI technique with navigator is demonstrated
      for anatomic and functional imaging studies on the human brain at 4 T.

PMID- 8744019
TI  - Fast 3D large-angle spin-echo imaging (3D FLASE).
AB  - A rapid steady-state 3D spin-echo imaging pulse sequence, based on the principle
      of nutating the spins by an angle greater than 90 degrees, has been designed and
      implemented on a clinical 1.5-T whole-body MR scanner. The pulse sequence,
      denoted fast large-angle spin-echo (FLASE), has been optimized for high
      resolution imaging of tissues with short T2 and T2*. Features of FLASE include a
      minimum-phase Shinnar-Le Roux excitation pulse and distribution of phase- and
      slice-encoding gradients before and after the 180 degrees refocusing pulse to
      minimize the critical time delay between inversion and restoration of the
      residual longitudinal magnetization and for minimizing echo time. A Bloch
      equation analysis, corroborated by experimental data, shows FLASE signal-to-noise
      to be superior to its closest analog, 3D rapid spin-echo excitation (RASEE) (Jara
      et al., Magn Reson Medicine 29, 528 (1993)), and 3D gradient-recalled acquisition
      in steady state (GRASS). It is demonstrated that with judicious RF phase-cycling
      and steady state operation, FLASE can produce high-quality microimages free of
      intravoxel phase dispersion from susceptibility-induced background gradients. The
      performance of the method is exemplified with ultra high-resolution images of
      trabecular bone in vitro and in vivo in the human calcaneus and wrist at voxel
      sizes as low as 98 x 98 x 200 microns3. Finally, the contrast behavior of
      refocused FLASE can be altered by disrupting the steady state analogous to
      gradient echo imaging.

PMID- 8744020
TI  - A modified sub-second fast-STEAM sequence incorporating bipolar gradients for in
      vivo diffusion imaging.
AB  - A modified high-speed stimulated-echo acquisition mode (STEAM) diffusion sequence
      (90 degrees-TE/2-90 degrees-TM-[alpha-TE/2-STE]n) incorporating bipolar diffusion
      gradients that are less sensitive to macroscopic motion-induced artifacts is
      presented. Diffusion encoding was performed only during the first echo interval
      (TE1) with bipolar gradients that were implemented on all three mutually
      orthogonal axes. Calibration measurements on phantoms filled with water,
      isopropanol, and dimethyl sulfoxide yielded apparent diffusion coefficients (ADC)
      consistent with published values. Non-ECG-triggered in vivo images acquired on
      rat brain with relatively high b values (approximately 450 s/mm2) indicated
      minimal motion artifacts. Evaluated ADCs averaged over the cortex, left mid
      brain, right mid-brain, regions yielded (0.91 +/- 0.02), (1.06 +/- 0.02), (1.01
      +/- 0.03) x 10(-3) mm2s-1, respectively.

PMID- 8744021
TI  - Improvement of measurement precision in absorption spectra by apodization.
AB  - In in vivo MR spectroscopy studies, it is desirable to determine metabolite peak
      parameters with good precision and to estimate the uncertainties. How to achieve
      optimal precision for an apodized MR spectrum by using a weighted least squares
      estimator is discussed and demonstrated. Analytic methods for calculating the
      uncertainties of all parameters obtained from least squares estimators are
      described. The time domain apodization before Fourier transformation can
      substantially decrease the minimum variance bound in parameters obtained from the
      frequency domain absorption spectrum. A weighted least squares estimation is
      needed to reach the Cramer-Rao lower bound. When an unweighted least squares
      estimation is performed, the time domain apodization also leads to improvement in
      precision.

PMID- 8744022
TI  - Decay characteristics of bone marrow in the presence of a trabecular bone
      network: in vitro and in vivo studies showing a departure from monoexponential
      behavior.
AB  - In this study, we examine MRI T2' decay characteristics for bone marrow in
      trabecular bone networks, using an asymmetric spin-echo sequence to isolate the
      inhomogeneous decay due to susceptibility variations between bone and marrow or
      water. In in vitro measurements on trabecular bone specimens from human vertebral
      bodies, tibia, and radii, we find significant deviations from a monoexponential
      signal decay. The initial decay is seen to have a Gaussian decay character,
      switching to a primarily exponential decay at later decay times. A similar trend
      is observed in in vivo measurements in the distal radius. Unlike an exponential
      decay, which may be characterized by a single decay rate, this is indicative of a
      significant variation in the decay rate with time. The deviations from
      exponential decay are seen to be orientation dependent, being most significant
      when the primary trabecular orientation is perpendicular to the static magnetic
      field.

PMID- 8744023
TI  - Design of conformationally rigid dimeric MRI agents.
AB  - The conformational flexibility of the linkage mechanism or tether between
      paramagnetic metal centers is explored to assess optimal structural
      characteristics of multimeric MRI contrast agents. Two dimeric paramagnetic
      chelates differing in linkage flexibility but similar in symmetry are compared
      Relaxivity, water hydration number, and reorientational times of the chelate
      groups are obtained, and the results demonstrate that greater linkage flexibility
      reduces overall relaxivity.

PMID- 8744024
TI  - The molecular basis for disease variability in cystic fibrosis.
AB  - Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in
      the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The disease
      is characterized by a wide variability of clinical expression. The cloning of the
      CFTR gene and the identification of its mutations has promoted extensive research
      into the association between genotype and phenotype. Several studies showed that
      there are mutations, like the delta F508 (the most common mutation worldwide),
      which are associated with a severe phenotype and there are mutations associated
      with a milder phenotype. However, there is a substantial variability in disease
      expression among patients carrying the same mutation. This variability involves
      also the severity of lung disease. Furthermore, increased frequencies of
      mutations are found among patients with incomplete CF expression which includes
      male infertility due to congenital bilateral absence of the vas deferens. In
      vitro studies of the CFTR function suggested that different mutations cause
      different defects in protein production and function. The mechanisms by which
      mutations disrupt CFTR function are defective protein production, processing,
      channel regulation, and conductance. In addition, reduced levels of the normal
      CFTR mRNA are associated with the CF disease. These mutations are associated with
      a highly variable phenotype from healthy individuals or infertile males to a
      typical CF disease. This variability in disease expression is associated with
      different levels of normally spliced transcripts. Further understanding the
      mechanisms of CFTR dysfunction may suggest different therapeutic strategies for
      each class of mutations.

PMID- 8744025
TI  - Frequency distributions of apolipoprotein(a) kringle IV repeat alleles and their
      effects on lipoprotein(a) levels in Caucasian, Asian, and African populations:
      the distribution of null alleles is non-random.
AB  - A size polymorphism (K IV VNTR) and largely unknown sequence variation in the
      apolipoprotein(a) [apo(a)] gene on chromosome 6q26-q27 together determine most of
      the extreme variation in apo(a) glycoprotein expression and lipoprotein(a)
      [Lp(a)] plasma concentration in Caucasians. We have determined Lp(a) plasma
      concentrations, the number of kringle IV (K IV) repeats in the apo(a) gene and
      the expression of the apo(a) glycoprotein in four ethnic groups (Khoi San, South
      African Blacks, Hong Kong Chinese and Caucasians from the Tyrol, total n = 788).
      The distributions of Lp(a) concentrations, the frequencies of expressed and non
      expressed apo(a) K IV alleles, and the impact of the size polymorphism on Lp(a)
      concentrations were all heterogeneous across populations. In contrast, the effect
      of the K IV repeat alleles appeared homogeneous. Lp(a) concentrations were higher
      in Africans and Chinese than in Caucasians, but this was not explained by
      differences in K IV repeat allele frequencies among populations. Lp(a)
      concentrations were highest in Khoi San, suggesting that high Lp(a) is an old
      African trait. When expressed as Spearman rank correlations the impact of the
      size polymorphism was smallest in African Blacks (R = -0.386) and largest in the
      Chinese (R = -0.692). In all four populations, the distribution of non-expressed
      apo(a) alleles was non-random. Rather they were significantly associated with
      distinct size alleles and overall positively with high K IV repeat numbers. The
      negative correlation of K IV repeat length with Lp(a) concentration was non
      linear in Khoi San and the average apo(a)-size-allele-associated Lp(a)
      concentrations were markedly different between all populations. We conclude that
      besides the apo(a) size variation, other factors affect Lp(a) concentrations to
      different degrees in the study populations. Most likely, this is sequence
      variation in apo(a) which is not the same in the different ethnic groups.

PMID- 8744026
TI  - Clinical heterogeneity in 16 patients with inv dup 15 chromosome: cytogenetic and
      molecular studies, search for an imprinting effect.
AB  - We report on clinical, cytogenetic and molecular analyses of 16 patients with inv
      dup (15) chromosome. We define the content of the inv dup (15) markers, their
      meiotic origin and the methylation status of the chromosome region involved.
      Precise phenotype-karyotype-genotype correlations allowed the identification of
      five different types of marker and demonstrated that even when the molecular
      content of the inv dup (15) chromosome clearly contributes to the severity of the
      phenotype, it does not appear to be the only relevant factor. All the markers
      were of maternal origin with an identical methylation profile, and neither
      imprinting nor methylation can explain the phenotypic variability. We suggest
      that the degree of phenotypic severity may be correlated with the severity of
      epilepsy.

PMID- 8744027
TI  - An Xp22.1-p22.2 YAC contig encompassing the disease loci for RS, KFSD, CLS, HYP
      and RP15: refined localization of RS.
AB  - To facilitate the positional cloning of the genes involved in retinoschisis (RS),
      keratosis follicularis spinulosa decalvans (KFSD), Coffin-Lowry syndrome (CLS), X
      linked hypophosphatemic rickets (XLH, locus name HYP) and X-linked dominant cone
      rod degeneration (locus name RP15), we have extended the molecular map of the
      Xp22 region. Screening of several YAC libraries allowed us to identify 156 YACs,
      52 of which localize between markers DXS414 (P90) and DXS451 (kQST80H1). Analysis
      of their marker content facilitated the construction of a YAC contig from the
      region spanning (in this order): DXS414 - DXS987 - DXS207 - DXS1053 - DXS197 -
      DXS 43 - DXS1195 - DXS418 - DXS999 - PDHA1 - DXS7161 - DXS443 - DXS 7592 -
      DXS1229 - DXS365 - DXS7101 - DXS7593 - DXS1052 - DXS274 - DXS989 - DXS451. The
      region between DXS414 and DXS451 covers about 4.5-5 Mb. Two additional markers
      (DXS7593 and DXS7592) were placed in the region, thereby increasing the genetic
      resolution. Using the deduced marker order, the analysis of key recombinants in
      families segregating RS allowed us to refine the critical region for RS to 0.6
      Mb, between DXS418 and DXS7161.

PMID- 8744028
TI  - Autosomal recessive lamellar ichthyosis and acute lymphoblastic leukemia.
AB  - Autosomal recessive lamellar ichthyosis (ARLI) is a congenital disorder of
      keratinization, the gene of which has been mapped to chromosome 14q11. This band
      is also the breakpoint in various chromosomal rearrangements in T cell acute
      lymphoblastic leukemia (ALL). We describe a patient with ARLI who developed ALL
      at the age of 2.5 years. High resolution banding showed no abnormality or
      rearrangement involving chromosome 14. To our knowledge, this is the first
      description of the occurrence of the two conditions in one patient.

PMID- 8744029
TI  - Audit of maternal serum screening: strategies to augment counselling in response
      to women's views.
AB  - Women's opinion on the maternal serum screening programme offered at one
      maternity unit in East Northumberland (1991-1992) was evaluated. The responses
      from 1,774/2,633 women showed a general acceptance of the test but 722/1,774
      (40%) wanted more information and a third, more explanation. Recommendations,
      which included a 'gold standard' protocol, a video to complement revised patient
      information literature and a coordinator to facilitate interdisciplinary
      communication and training with support for midwives, were introduced. The audit
      cycle was completed by a repeat questionnaire survey of 2,489 women from the
      postnatal ward (1992-1994) with a 67.3% response. An overall improvement in
      levels of satisfaction with reduction in, but not eradication of, the need for
      more information and explanation had occurred. These findings have relevance to
      the current controversy surrounding the counselling implications of maternal
      serum screening and have led to the formation of a network of professionals to
      develop the programme in our region.

PMID- 8744030
TI  - Experiences of mothers participating in maternal serum screening for Down's
      syndrome.
AB  - The participation rate in a maternal serum screening for trisomy 21 was 84% in
      the Helsinki trial. Six hundred and twenty-five mothers who had a positive result
      and a random sample of 245 mothers who had a negative result took part in the
      opinion survey. Ninety-five percent of the first and 97% of the second group
      considered the screening tests as very or quite useful. However, 12% of those
      with a positive result would decide against taking the test if they could
      reconsider, whereas 100% of those with a negative result would take it again. Too
      little information about the test, worries and stress, unnecessary in cases of
      false timing, difficult decision-making, and anxiety while awaiting the results
      of the chromosome study were the main complaints. More information at all stages,
      earlier testing, ultrasound timing before the serum test, and fast results were
      considered essential.

PMID- 8744032
TI  - Predictors of and therapeutic strategies in progressive chronic renal disease.

PMID- 8744031
TI  - Psychological impact of carrier screening for cystic fibrosis among pregnant
      women.
AB  - The aim of the present study was to assess the impact of being identified carrier
      of cystic fibrosis. The impact was assessed in terms of retention of the result,
      sharing of the information about the result with relatives, non-relatives and
      GPs, changes in reproductive plans, and regrets about having been tested Three
      unsupervised questionnaires were sent to 160 women identified as carriers between
      1990 and 1992 in June 1992, October 1993, and November 1994. Carriers freely
      shared the information about their result with relatives, friends, and GPs. The
      inconclusiveness of the test gave rise to some confusion. This may reflect
      inadequacies in the information and counselling given to carriers, but
      psychological factors are also believed to be responsible. Thus, false
      reassurance may be a problem in a carrier screening with a test that detect only
      a proportion of carriers. Few carriers considered changing their reproductive
      plans due to the result of the test. A few women identified as carrier regretted
      having had the test.

PMID- 8744033
TI  - Mechanisms and implications of heterogeneity of human glomerulosclerosis.

PMID- 8744034
TI  - Involvement of synthesis and degradation pathways of collagen type IV in human
      glomerulosclerosis: molecular analysis by in situ reverse transcription and
      competitive polymerase chain reaction.

PMID- 8744035
TI  - Lipids and progressive renal failure.

PMID- 8744036
TI  - Cisplatin-induced apoptosis in mouse proximal tubular cell line.

PMID- 8744037
TI  - Glomerular capillary regeneration and endothelial cell apoptosis in both
      reversible and progressive models of glomerulonephritis.
AB  - In summary, angiogenetic capillary regeneration with endothelial proliferation
      occurred among mesangiolytic lesions in Thy-1 GN, and the damaged glomerulus
      recovered its normal structure with the reconstruction of the capillary network.
      In anti-GBM GN on WKY rats, the damaged glomerulus showed rare capillary
      regeneration and progressed to global sclerosis. In Thy-1 GN, endothelial cell
      apoptosis was found in the regenerated capillaries with endothelial cell
      hypercellularity. On the other hand, in anti-GBM GN on WKY rats, the number of
      endothelial cell apoptosis increased during the evolution of glomerular
      sclerosis. We have concluded that glomerular capillary regeneration plays an
      essential role in the recovery of damaged glomeruli. Moreover, apoptosis is
      indispensable in regulating the number of intrinsic endothelial cells. We also
      found that endothelial apoptosis is important in progression of glomerular
      sclerosis.

PMID- 8744038
TI  - Role of apoptosis in the progression of glomerulosclerosis.

PMID- 8744039
TI  - Expression of apoptosis-preventing Bcl-2 protein and -inducing Fas antigen in
      glomeruli of IgA nephropathy.

PMID- 8744040
TI  - Glomerular healing.

PMID- 8744041
TI  - Tumor necrosis factor in glomerular injury.

PMID- 8744042
TI  - The role of basic fibroblast growth factor (FGF2) in glomerular epithelial cell
      injury.

PMID- 8744043
TI  - TGF-beta behavior in the progressive process in the focal glomerulosclerosis rat
      model: the role of latent TGF-beta-binding protein.

PMID- 8744044
TI  - Application of antisense oligodeoxynucleotides (ODNs) for the intervention of
      kidney disease. Antisense ODNs for transforming growth factor-beta-suppressed
      glomerulosclerosis in experimental glomerulonephritis.

PMID- 8744045
TI  - Gene transfer of macrophage growth factors into the kidney of lpr mice initiates
      renal injury.

PMID- 8744046
TI  - Local macrophage proliferation in progressive renal injury.

PMID- 8744047
TI  - CD8+ lymphocytes play a central role in the development of anti-GBM nephritis
      through induction of ICAM-I and chemokines in WKY rats.

PMID- 8744048
TI  - Lipoxygenases as therapeutic targets in the acute and subacute phases of
      glomerular immune injury.

PMID- 8744049
TI  - Abnormalities in extracellular matrix regulation in autosomal dominant polycystic
      kidney disease.

PMID- 8744050
TI  - Activation of metalloproteinase-2 by membrane type metalloproteinase expressed on
      human mesangial cell membrane.

PMID- 8744051
TI  - Advanced glycosylation end products modulate transcriptional regulations on
      mesangial cells.

PMID- 8744052
TI  - Possible mechanisms of renal fibrosis.

PMID- 8744053
TI  - Effect of a specific endothelin receptor A antagonist on murine lupus nephritis
      and IgA nephropathy.

PMID- 8744054
TI  - Proteins abnormally filtered throughout glomerular capillary have an intrinsic
      renal toxicity.

PMID- 8744055
TI  - Proteinuria: a mediator of interstitial fibrosis?

PMID- 8744056
TI  - Role of protein kinase C in glucose- and angiotensin II-induced plasminogen
      activator inhibitor expression.

PMID- 8744058
TI  - The structure of glomeruli and juxtaglomerular arterioles in the early phase of
      diabetic nephropathy--relationship between progression and metabolic control.

PMID- 8744057
TI  - The use of neutralizing antibodies to demonstrate the role of transforming growth
      factor-beta and Amadori-glycated albumin as mediators of experimental diabetic
      kidney disease.

PMID- 8744059
TI  - Angiotensin-converting enzyme inhibition in type I diabetic nephropathy.

PMID- 8744060
TI  - Autocrine secretion of angiotensin II mediates stretch-induced hypertrophy of
      cardiac myocytes in vitro.

PMID- 8744061
TI  - Alteration of cellular function in rat mesangial cells in response to mechanical
      stretch relaxation.

PMID- 8744062
TI  - Glomerular hypertension and progressive renal disease: the interplay of mesangial
      cell stretch, cytokine formation and extracellular matrix synthesis.

PMID- 8744063
TI  - Evidence for the role of angiotensin in the establishment and maintenance of
      renal morphology.

PMID- 8744064
TI  - Modulation of renin release and renal vascular smooth muscle cell contractility
      by TGF-beta 2.

PMID- 8744065
TI  - Role of angiotensin-converting enzyme gene polymorphism in progressive loss of
      renal function in chronic renal diseases.

PMID- 8744067
TI  - [Involuntary commitment in psychiatry].

PMID- 8744066
TI  - Novel strategy of gene therapy in cardiovascular disease with HVJ-liposome
      method.

PMID- 8744068
TI  - [The law on involuntary commitment and other detaintment in psychiatry. A study
      of registered involuntary commitments].
AB  - The hospitals included in this study receive about 20% of all commitments to
      mental hospitals in Denmark. The investigation showed that 4% of the commitments
      were involuntary. The median time for involuntary detainment was 12 days. More
      than half of the patients who were committed on an involuntary basis experienced
      involuntary detainment. But 70% of all involuntary detainments were experienced
      by patients who were committed on a voluntary basis. The study suggests that a
      high bed occupancy rate together with poor out-hospital treatment of the patients
      might lead to a higher number of compulsory admissions. Other factors may be of
      importance but were not considered in this study. According to Danish law all
      compulsory admissions and detainments must be reviewed according to certain
      rules. The investigation showed that there were some irregularities concerning
      such reviewing. The number of staff members including doctors has not increased
      despite the fact that reviewing commitments and detainments takes a lot of time
      for the staff involved.

PMID- 8744069
TI  - [Involuntary commitment in psychiatry of persons aged 65 and older].
AB  - The aim of the study was to examine the dimensions and the nature of the
      deprivations of liberty to which psychiatric patients of 65 years of age and
      older are exposed. The diagnostic pattern of these patients was also
      investigated. The case records of 97 elderly patients that had been exposed to a
      deprivation of liberty during the five year period from 1 October 1989 to 30
      September 1994 were reviewed. There were 63 compulsory commitments to the
      psychiatric department in Ballerup during this period. More elderly patients were
      committed due to a need for treatment (yellow admission papers) than due to their
      being dangerous to themselves or other people (red admission papers). There were
      proportionately more compulsory than voluntary commitments among patients of 65
      years of age and over than among patients under the age of 65. Elderly women
      committed for treatment (yellow admission papers) were deprived of their liberty
      for a longer period than elderly men committed for the same reasons. The most
      frequent diagnosis on discharge from the hospital was senile dementia. There is a
      different pattern of deprivation of liberty among elderly psychiatric patients
      than among those under the age og 65. The legal aspects surrounding the largest
      group of elderly compulsory commitments have not yet been satisfactorily
      clarified.

PMID- 8744070
TI  - [Use of restraints before and after the new psychiatric law].
AB  - The purpose of this research project was to examine, in retrospect, the effect of
      certain factors on the incidence of the use of restrains before and after the
      introduction of the Danish law reform concerning compulsory treatment. Data
      concerning the use of restraints on four locked wards in the Psychiatric
      Department of Glostrup Hospital during a six-month period in 1988 were compared
      with equivalent data from a six-month period in 1991. It was found that the law
      reform had no statistically significant influence on the incidence of the use of
      restraints. Factors such as high bed occupancy rate and shortage of staff did not
      lead to a higher incidence of use of restraint.

PMID- 8744071
TI  - [The use of coercion at psychiatric departments for adults, Hillerod hospital. A
      descriptive study of the period 10 January 1991-31 August 1992].
AB  - The study describes the type and amount of coercion used during 11 months of
      1992. Four hundred and fourty-one cases were included. Young patients i.e. 10 to
      29 years old, demented patients and patients suffering from organic psychoses
      were, overall, more often subjected to coercive measures. When looking at each
      type of coercion separately, it was found that detainment, compulsive treatment
      and fixation were especially used on the young and on patients suffering from
      schizophrenia. However, fixation used as a protective measure was mainly used on
      the demented and the 60 to 79 year-old patients.

PMID- 8744072
TI  - [The significance of ixidized low density lipoprotein in atherosclerosis].
AB  - The "oxidation hypothesis" states that oxidised low-density lipoprotein (ox-LDL)
      plays a central role in atherogenesis. LDL oxidation is a chaotic process
      initiated by reactive oxygen species. Enhanced uptake of ox-LDL in macrophages
      leads to foam cell formation in vitro, and ox-LDL has a variety of other
      experimental proatherogenic effects, e.g., endothelial cell activation,
      immunogenicity, platelet aggregation, and inhibition of endothelium-dependent
      vaso-relaxation. There are methodological limitations in the current laboratory
      methods aimed at characterization of the oxidative state of LDL. However,
      considerable evidence indicates that ox-LDL is found in plasma, arteries, and
      atheromatous plaques of humans, although the significance of this phenomenon is
      unknown. Antioxidants may inhibit atherosclerosis in experimental animals, and
      epidemiological data suggest an inverse relation between the intake of
      antioxidant vitamins and the risk of coronary artery disease. Randomised
      prospective trials are in progress, and until their conclusion, the clinical
      effect of antioxidant therapy in man remains unknown.

PMID- 8744073
TI  - [Sotalol and torsades de pointes ventricular tachycardia].
AB  - Sotalol is together with amiodarone the most effective antiarrhythmic. Compared
      to class I antiarrhythmics it has less mortality. However, sotalol can, like
      class IA antiarrhythmics, release life-threatening attacks of torsade de pointes
      ventricular tachycardia (TdP-VT), as proarrhythmia or by overdosing. TdP-VT
      appears in 2% of all patients treated with sotalol. In patients treated for
      ventricular tachycardias TdP-VT appears in 4%. Some factors increase the
      incidence of TdP-VT: reduced left ventricular function, hypokalaemia,
      hypomagnesiaemia, bradycardia, extended QT-interval and daily doses exceeding 320
      mg. We recommend increased attention to these predisposing factors so as to
      prevent TdP-VT. Pharmacologically induced TdP-VT may be misdiagnosed as "genuine"
      ventricular tachycardia. This often results in increased doses of sotalol, which
      worsen the TdP-VT. Sotalol is renally excreted and TdP-VT can appear in patients
      with reduced renal function where normal doses are used. QTC prolongation above
      550 ms. or severe bradycardia indicates risk of TdP-VT and should result in end
      of treatment or dose-reduction. Six case-stories are presented.

PMID- 8744074
TI  - [Late recurrence of stomach cancer in a patient treated with a H2 receptor
      antagonist].
AB  - We report a case where a patient developed recurrence of an adenocarcinoma of the
      stomach ten years after primary surgery. Besides the late recurrence, the case is
      interesting as the patient participated in a trial investigating the effect of
      cimetidine on survival after gastric cancer and received cimetidine for two years
      after surgery. Considering the well documented anti-tumour and immunomodulating
      effects of histamine type-2 receptor antagonists, it might be interesting to
      examine the effect on survival after surgery for gastric cancer in patients
      receiving prolonged treatment with such an antagonist.

PMID- 8744075
TI  - [Training in gynecologic-obstetric ultrasonic diagnosis].

PMID- 8744076
TI  - [Erythema multiforme and Stevens-Johnson syndrome are not variants of the same
      disease].

PMID- 8744077
TI  - [What connection is there between body weight and mortality?].

PMID- 8744078
TI  - [Daytime urinary incontinence in children--is it treatable?].

PMID- 8744079
TI  - The social production of authoritative knowledge in pregnancy and childbirth.

PMID- 8744080
TI  - "Women come here on their own when they need to": prenatal care, authoritative
      knowledge, and maternal health in Oaxaca.
AB  - Physiological and anatomical concepts about reproduction held by traditional
      midwives in Southern Oaxaca differ considerably from those of biomedicine.
      Government training courses for traditional midwives disregard these deep-seated
      differences, and also the underlying conceptual rationale of ethno-obstetrics.
      These courses constantly reinforce and actively promote the biomedical model of
      care. But rural midwives, despite these training courses, do not substantially
      change their obstetrical vision and ways. The strength of their own authoritative
      knowledge, fully shared by the women and men of their communities, allows them to
      continue their traditional style of care, despite pressures to conform to
      biomedical values, beliefs, and practices. Suggestions for a mutual accommodation
      of biomedical and midwifery approaches to prenatal care include training medical
      personnel in ethno-obstetric techniques and rationales, teaching midwives basic
      medical interventions, addressing in intervention programs all social actors
      participating in reproductive decision making, and adopting an interdisciplinary
      approach that includes nonmedical aspects of maternal care.

PMID- 8744081
TI  - The production of authoritative knowledge in American prenatal care.
AB  - Using Jordan's concept of authoritative knowledge, this article describes some of
      the ways that the prenatal care practices of a group of U.S. women help to
      consolidate biomedical hegemony. We analyze the considerations that the women
      took into account when deciding whether or not to accept specific prenatal care
      recommendations as authoritative, focusing on when and how they used their own
      "embodied" knowledge and experience as a standard against which to assess the
      validity of clinical recommendations. The data provide insight into
      medicalization processes and the role patients themselves play in furthering
      biomedical hegemony.

PMID- 8744082
TI  - Fetal ultrasound imaging and the production of authoritative knowledge in Greece.
AB  - In Greece repetitive and intensive fetal scanning is now a universal feature of
      prenatal care. This article examines some of the ways in which pregnant women and
      obstetricians experience the intensive use of fetal ultrasound in a small city in
      eastern Greece. Based on observations and interviews conducted in a public
      hospital, it is argued that fetal imaging plays a privileged role in the
      production of authoritative knowledge around pregnancy for both doctors and
      women. The authority of the technology rests primarily on its ability to create a
      straightforward sense of reality and visual pleasure. These qualities lead women
      to actively demand fetal scanning, which helps them to feel the reality of their
      pregnancies, reassures them of fetal health, and provides a pleasurable sense of
      contact with, and knowledge about, the fetus. Doctors freely offer multiple scans
      to attract women to the public hospital, to practice "modern" obstetrics, and to
      negotiate among themselves for control over the management of pregnant women.

PMID- 8744083
TI  - Fetal rights versus the female body: contested domains.
AB  - This article examines the debates surrounding the personhood of the fetus in
      relationship to the mother as these issues were socially constructed in the
      Mississippi state legislature in 1990 and 1991. In examining the patriarchal
      assumptions that underlay the proposed Mississippi legislation, the article also
      addresses the legal ramifications of defining the fetus as a person whose rights
      are posited as equal to, or greater than, those of the pregnant woman. By relying
      on medical/scientific definitions of personhood, the groundwork for further
      refinement and monitoring of women and fetuses is being established, such that
      what it means to be human is increasingly defined in essentialist terms. In the
      final evaluation, focusing on conception as the moment in which an "unborn child"
      is created sets the stage for the ultimate essentialist metaphor: a eugenic
      definition of personhood.

PMID- 8744084
TI  - Authoritative knowledge and birth territories in contemporary Japan.
AB  - In Japan, as in the United States, the change from home to health care
      institution as the location of birth has been marked by depicting the
      obstetrician as having authoritative knowledge about birthing. The obstetrician's
      access to and control over specialized obstetrical technology reflect and
      legitimate his authoritative status. In Japan a prevailing cultural view of birth
      as a natural and healthy event places a value on using the least possible amount
      of obstetrical intervention in the birthing process. This results in the
      valuation of the potential, rather than the actual, application of obstetrical
      technology. In contemporary Japan midwives remain integral participants in
      maternity care and attend normal deliveries in the hospital setting. But because
      of the culturally depicted potential for pathology at the time of birth, the
      obstetrician-the birthing specialist who controls the more complex technological
      tools-is viewed as having greater authoritative knowledge than the midwife and
      the woman giving birth.

PMID- 8744085
TI  - Ways of knowing about birth in three cultures.
AB  - This article examines the concept of authoritative knowledge elaborated by
      Brigitte Jordan, using examples of birthing systems in Mexico, Texas, and
      Jamaica. We explore the linkages between the distribution of knowledge about
      birth and the use of technology; the valuation of biomedical and alternative
      "ways of knowing" about birth; the production of authoritative knowledge through
      interaction; and the relationship between authoritative knowledge and social
      status. In the Maya low-technology, collaborative birthing system in Mexico, the
      midwife and other adult women share knowledge about birth. In contrast, Spanish
      speaking women undergoing cesarean delivery in a high-technology public hospital
      in Texas are, due to their limited English, only minimally able to interact with
      hospital staff. While they acknowledge the authoritative position of biomedical
      personnel and value technology, they protest their inability to communicate
      during their hospitalization. Jamaican women deliver in a formerly high
      technology hospital system that is now experiencing economic austerity measures
      that render it increasingly dysfunctional. While use of technology is infrequent
      in the Jamaican case, authoritative knowledge remains vested in biomedicine. By
      means of three examples we respond to Jordan's call for a rethinking of
      authoritative knowledge in high- and low-technology settings.

PMID- 8744086
TI  - Intuition as authoritative knowledge in midwifery and homebirth.
AB  - As defined by Jordan (1992, 1993[1978]), authoritative knowledge motivates
      decision and action. Based on interviews with 22 white middle-class midwives in
      the United States conducted between 1992 and 1993, this article explores the
      inner knowing that constitutes a primary source of authoritative knowledge for
      homebirthers but is granted no authority in the realm of technomedicine. The
      purpose of this article is to call attention to these midwives' utilization of
      and reliance on intuition as a guide to action and decision making during
      homebirths. The midwife-interviewees are highly literate and competent in
      technological skills and biomedical diagnosis, and are keenly aware of the
      cultural and legal risks they run when they cannot justify their actions during a
      birth in logical, rational terms. Nevertheless, the deep value they place on
      connection, in the context of their holistic model of birth and health care,
      leads them to listen to and follow their "inner voice" during birth, rather than
      operating only according to protocols and standard parameters for "normal birth".
      The nature of intuition and the reasons for and consequences of the general
      devaluation of intuitive thinking by the wider society are also considered.

PMID- 8744087
TI  - Maternal health, war, and religious tradition: authoritative knowledge in Pujehun
      District, Sierra Leone.
AB  - In Sierra Leone constraints to ideal maternal health require a primary health
      care approach that includes collaboration with traditional midwives. They are
      authoritative figures embedded within local political structures and a powerful
      women's religion. The local causes of maternal risk are described, including
      civil war and refugee camp life. Traditional midwives provide vital services in
      the camp, are respected for their social status, and learn additional skills.
      Biomedical and traditional systems of authoritative knowledge, based on different
      kinds of legitimacy to heal, are in a complementary relationship.

PMID- 8744088
TI  - The evolution of bipedalism and assisted birth.

PMID- 8744089
TI  - Authority and authoritative knowledge in American birth.

PMID- 8744090
TI  - Intuition and the emergence of midwifery as authoritative knowledge.

PMID- 8744091
TI  - [Respiratory organ pathology in those who cleaned up the aftermath of the
      accident at the Chernobyl Atomic Electric Power Station].

PMID- 8744092
TI  - [Respiratory organ pathology in the participants in the cleanup of the accident
      at the Chernobyl Atomic Electric Power Station].
AB  - The authors performed this investigation to ascertain the role of radioactive
      dust inhalation in the onset of respiratory diseases and determination of
      clinicomorphological features of such pathology. The authors have found that work
      in conditions of massive dust exposure, stay in the dust zone for a month and
      longer in 1986-1987 were the decisive risk factors of respiratory impairment. The
      examination covered 28 patients who had acute symptoms of inhalation damage to
      respiratory system when performing their job in the contaminated zone. Later on
      they developed chronic progressive respiratory affection having the following
      clinicomorphological characteristics: 1) persistent cough with hard to
      expectorate sputum, addition of respiratory insufficiency, sluggish recurrent
      infection and inflammation, deterioration of working capacity and quality of
      life, 2) isolated decline of specific diffuse capacity of the lungs in
      combination with obstructive ventilation, 3) marked disturbances of cellular
      immunity (reduced fraction of T-helpers and increased fraction of T-suppressors),
      4) x-ray picture of diffuse pneumosclerosis and hyperairiness of the lung tissue,
      5) endoscopic evidence of inflammation and atrophy of the bronchial tree mucosa,
      6) numerous alveolar macrophages with foreign inclusions in the lavage fluid,
      such markers of Chernobyl dust inhalation as Sr, Zr, I, Cs, Ce, Np, Pu, Am, Cm
      registered in alveolar macrophages at roentgenospectral and roentgenofluorescent
      microtests, 7) defective functional activity of alveolar macrophages (free
      radical activation). Long-term persistence of the Chernobyl dust in the lung
      tissue results in essential functional and morphological changes in cell
      composition of the alveolar area, lung tissue undergoes structural alterations
      contributing to specific respiratory diseases with typical clinicomorphological
      characteristics.

PMID- 8744093
TI  - [Respiratory tract damage in those who cleaned up the aftermath of the accident
      at the Chernobyl Atomic Electric Power Station].
AB  - The authors have established the fact of acute inhalation damage of the
      "Chernobyl aerosol" to respiratory organs of the exposed subjects. The complaints
      correlation to the site of work, time and kind of job shows that respiratory
      symptoms arose more frequently in those members of emergency teams who arrived at
      the station in May, August-October 1986, March 1987, stayed for 30-40 days,
      worked at the site of the damaged reactor, were engaged in decontamination,
      degasification, drilling, construction and other "dusty" jobs. As a result of
      inhalation of the Chernobyl dust previously healthy patients developed various
      respiratory diseases.

PMID- 8744094
TI  - [Respiratory and hemodynamic disorders in the participants in the cleanup of the
      aftermath of the accident at the Chernobyl Atomic Electric Power Station].
AB  - After examination of cardiorespiratory function in 10 males exposed to Chernobyl
      accident unfavorable factors at the age of 31-45 years suffering from chronic
      obstructive bronchitis (7 cases) and mixed bronchial asthma (3 cases) it was
      established that the patients had ventilation disorders of mixed genesis
      (moderate obstructive and respiratory affections), frequently occurring decreased
      specific diffusion (DLCO/Va) in normal total diffusion capacity of the lungs,
      inefficient gas exchange, midly declined left ventricular pump capacity and
      contractility. In the above patients a relationship was found between parameters
      of central hemodynamics assessed at echo-CG and severity of ventilation
      impairment and respiratory insufficiency.

PMID- 8744095
TI  - [The prevalence of respiratory organ diseases among those who cleaned up the
      accident at the Chernobyl Atomic Electric Power Station].
AB  - Epidemiological investigation of 206 males aged 30-45 exposed to radiation while
      working from May 1986 to March 1987 (the period of most likely radioactive dust
      inhalation damage) in radionuclide-contaminated zone after the Chernobyl accident
      has been performed. Chronic bronchitis and bronchial asthma occurred in the
      examinees 4.1 and 7.1 times more frequently than in nonexposed controls. The
      exposure to radionuclides was found related to subsequent respiratory disorders.
      Bronchopulmonary diseases in the emergency crews exposed to radiation were
      encountered in 42.5% which is two times more frequently than in control subjects.
      In view of this, it is necessary to introduce urgently special prophylactic
      programs for the above subjects.

PMID- 8744096
TI  - [The morphological characteristics of the alveolar macrophages in those who
      cleaned up the aftermath of the accident at the Chernobyl Atomic Electric Power
      Station at a late period (1)].
AB  - The paper presents morphological, morphometric and densitometric evidence
      obtained on cytoplasmic inclusions of alveolar macrophages from bronchoalveolar
      lavage of chronic obstructive bronchitis (COB) sufferers. All of them previously
      worked in the zone contaminated after the Chernobyl accident. The control
      consisted of nonexposed to radiation COB patients. In the exposed subjects
      alveolar macrophages were more active, 20% of cytoplasm was occupied by numerous
      phagolysosomes varying in form. Their densitometric evaluation has been
      performed. Further bronchoalveolar lavages will be conducted to follow up the
      above changes in alveolar macrophages.

PMID- 8744097
TI  - [The pathomorphology of the pulmonary infectious complications in acute radiation
      sickness (based on the autopsy data from persons who died as a result of the
      accident at the Chernobyl Atomic Electric Power Station].
AB  - The lungs from 27 patients who died from acute radiation sickness in Chernobyl
      accident were studied histologically. Pulmonary infectious complications were
      found caused by invasion of viral, bacterial and fungal agents. 2 cases with
      cytomegaloviral pneumonitis, 3 with focal bronchopneumonia and 3 with pulmonary
      candidiasis are described. Being dependent on hematopoietic function, the
      inflammatory reactions were not pronounced in postirradiation aplasia and became
      evident in the recovery.

PMID- 8744098
TI  - [The presence of cesium-137 in the tissue of a lung tumor in someone who cleaned
      up the aftermath of the accident at the Chernobyl Atomic Electric Power Station].
AB  - A man of 66 participated in the emergency works after the Chernobyl accident. His
      official dose of radiation comprised 24 roentgens. In March, 1993, he underwent
      prophylactic examination including computed tomography which revealed peripheral
      tumor in the lower part of the left lung with penetration in the lymph nodes of
      the lung root. Biopsy showed it to be adenocarcinoma. Moreover, electron
      microscopically, more than 40% of alveolar macrophages contained large optically
      dense particles in the cytoplasm. After lobectomy in March 1993 x-ray and gamma
      spectrometry of the removed lung tissue recorded high content of 137Cs (0.1-0.18
      Bq). This finding evidences possible long-term deposition of radionuclides in the
      bronchopulmonary system of radiation-exposed subjects.

PMID- 8744099
TI  - [The results of the combined programmed treatment of those who cleaned up the
      accident at the Chernobyl Atomic Electric Power Station who suffer from
      respiratory organ diseases].
AB  - Examination of respiratory system in subjects exposed to long-term inhalation of
      radioactive dust when engaged in repair works after the Chernobyl accident have
      revealed specific pathology of the respiratory organs caused by long-term
      persistence of radioactive dust in the lung tissue. A special regimen of combined
      treatment has been developed which included: bronchoalveolar lavage,
      antioxidants, broncholytics, mucolytics, extracorporeal procedures, physical
      rehabilitation. 1-year monitoring of subjects on this treatment versus untreated
      controls proved the above regimen beneficial as the patients exhibited less
      intensive clinical symptoms, less frequent exacerbations of infectious and
      inflammatory processes, higher quality of life. Some of the patients resumed
      work. Contrary to controls, the patients had no signs of progression. Therapeutic
      bronchoalveolar lavage led to elimination of a large percent of the radioactive
      dust which was present in the alveolar macrophages, thus ruling out the key
      factor of respiratory affections.

PMID- 8744100
TI  - [The rehabilitation under alpine conditions of the participants in the cleanup of
      the accident at the Chernobyl Atomic Electric Power Station who are ill with
      chronic bronchitis].
AB  - 24 patients exposed to low-dose radiation after the Chernobyl accident were
      examined before and after 24-day treatment of chronic bronchitis in the high
      altitude rehabilitation center (3200 m above the sea level) in Tien Shan.
      Sanogenic alpine climate improved the patients' general condition, physical
      performance and lung ventilation, corrected compromised immunity. After high
      altitude adaptation tracheobronchial inflammation alleviated, cytologic
      composition and surface activity of bronchoalveolar fluid returned to normal.
      Therefore, high-altitude treatment of Chernobyl accident victims with chronic
      bronchitis is effective and can be recommended for such patients.

PMID- 8744101
TI  - [An evaluation of the role of radiation and nonradiation factors in the
      development of lung cancer in workers at a radiochemical enterprise (1)].
AB  - A case-control study using logistic regression included 500 employees of the
      nuclear works (162 patients with lung carcinoma and 338 healthy controls). After
      examination of radiation and nonradiation causative factors 5 proved
      statistically significant. For them the following chance proportions were
      obtained: smoking 6.6, plutonium pneumosclerosis 4.6, plutonium incorporation
      3.1, chronic nonspecific pulmonary diseases 2.1, external gamma-radiation 1.6.
      Attributive risk for the total of the radiation factors makes up 25% at the most
      while of the nonradiation factors at least 70%.

PMID- 8744102
TI  - [The factors determining the late outcome in bronchial asthma: the role of the
      quality of medical care and of patient education].
AB  - Medical service to bronchial asthma (BA) outpatients and their education were
      assessed in a specially designed study of BA outcomes. Negative factors which
      contributed to unfavourable BA outcome were the following: formal approach of the
      physicians to the patients follow-up, the patients' noncompliance, their
      rejection to apply for medical aid in BA exacerbation, bad skills of self-care in
      grave BA attacks.

PMID- 8744103
TI  - [Psychoautonomic disorders in bronchial asthma patients].
AB  - The results of psychological and vegetative investigations in 142 patients with
      bronchial asthma (BA) demonstrated that BA gives rise to psychovegetative
      syndrome resultant from parasympathetic orientation of the vegetative tone and
      reactivity, weak vegetative support of muscular and mental activity. These
      vegetative shifts occur in line with enhanced ascending nonspecific activation
      and anxious-hypochondriac traits of personality.

PMID- 8744104
TI  - [The effect of the Russian inhalant glucocorticosteroid budesonide on bronchial
      inflammation and hyperreactivity during the long-term treatment of bronchial
      asthma patients].
AB  - 11 patients with severe bronchial asthma entered a randomized trial of
      glucocorticosteroid budesonide of Russian produce. Of them 6 patients received
      inhalations of budesonide (800 micrograms/day for 6 months), 5 control patients
      did not receive the drug. As shown by investigations of external respiration and
      bronchoalveolar lavage with estimation of cytogram, metacholine provocative
      tests, fiber bronchoscopy, budesonide inhalations relieved clinical symptoms of
      asthma, bronchial hyperreactivity and inflammation.

PMID- 8744105
TI  - [Cardiac monitoring in bronchial asthma patients taking salben].

PMID- 8744106
TI  - [The correction of biological defects in bronchial asthma patients by the methods
      of Chinese medicine].
AB  - 42 patients with bronchial asthma underwent combined treatment according to 8
      methods of classical Chinese medicine. Partial and complete immediate and long
      term responses were achieved in 81% of the patients with asthma diagnosed by
      Chinese criteria as cold and mixed. Satisfactory results were recorded in 19% of
      hot bronchial asthma cases.

PMID- 8744107
TI  - [The correlational analysis assessment of exacerbation in bronchial asthma and
      treatment efficacy].
AB  - Blood and sputum eosinophils, eosinophilic cation protein (ECP) in the serum and
      OPV1 were measured in 30 patients with atopic bronchial asthma (BA) of moderate
      severity showing eosinophilia at the beginning and the end of treatment week 1
      and 4, respectively. In exacerbation of BA relative number of blood eosinophils
      averaged 10.4 + -1.4%, sputum 35.2 + -5.6%. Serum concentration of ECP, OPV1, IgE
      averaged 42.6% + -11.9%, 66.8 + -6.3%, 753.7 + -114 IU/ml, respectively. In
      exacerbation a strong correlation is noted between relative number of eosinophils
      in the blood and sputum, between the levels of IgE and ECP. At the end of the
      treatment OPV1 was higher while ECP level in the serum went down. Reduced
      eosinophilia in the blood and sputum correlated with OPV1 increment. In BA
      patients with high blood and sputum eosinophilia function of the lungs depends on
      eosinophilic number, while in normalization of blood eosinophil concentration and
      in a sharp fall of sputum eosinophil number OPV1 changes correlation with changes
      in ECP in the course of treatment. A close correlation between changes in
      eosinophil count, FVD indices, IgE and ECP levels during the treatment indicate
      relief of inflammation in BA patients.

PMID- 8744108
TI  - [Chronic obstructive bronchitis: its pathogenetic aspects and the characteristics
      of its clinical course].
AB  - Lipid peroxidation (LPO) and antioxidant system (AOS) were examined in 40
      inpatients with chronic obstructive bronchitis (COB) on conventional treatment.
      The above parameters were considered in relation to clinical picture. It is shown
      that inflammation in the bronchial tree is associated with AOS functional
      deterioration and marked LPO intensification. A correlation was established
      between LPO activity, concentration of alpha-tocopherol in red cell membrane and
      degree of bronchial obstruction as well as remission quality. Persistent high
      intensity of LPO is suggested as an underlying cause of the disease transition to
      chronic form and progression of bronchial obstruction. Basing on the above
      observations, the authors insist on antioxidants introduction in COB treatment.

PMID- 8744110
TI  - [An initial trial of using pulsed hypoxia incorporating helium in the treatment
      of chronic obstructive bronchitis].

PMID- 8744109
TI  - [Methods for diagnosing the physiopathological mechanisms of bronchial
      obstruction].
AB  - This study aimed at clarification of pathophysiological mechanisms underlying
      bronchial obstruction in 28 18-71-year-old patients with chronic bronchitis (CB)
      diagnosed 2-8 years before. The patients had moderate obstructive disorders in
      distal parts of the bronchial tree. Investigations revealed a group of patients
      with paradoxical response to beta-blockers manifesting as lowering of bronchial
      resistance and high speed. Bronchial obstruction in these patients proved to
      arise primarily from early expiratory collapse of small bronchi. Administration
      of beta-mimetic and beta-blocking agents may serve as pharmacological tests able
      to discover mechanisms of bronchial obstruction and help in the choice of
      adequate therapy for chronic bronchitis.

PMID- 8744111
TI  - [Tuberculosis in patients with chronic kidney failure].

PMID- 8744112
TI  - [The diagnostic importance of determining tuberculosis antibodies by immunoenzyme
      analysis in exudative pleurisy].
AB  - High diagnostic value of EIA detection of antituberculous antibodies in
      recognition of tuberculous pleurisy was established after examination of 58
      patients with pleural exudate of different origin (tuberculous, tumor,
      nonspecific). Tuberculous pleurisy was diagnosed using sonicate M. tuberculosis
      as the antigen. It is important to determine antituberculous antibodies
      simultaneously in blood serum and exudate because in such a way it becomes
      possible to raise the test specificity to 100% in high sensitivity (94.7%).

PMID- 8744113
TI  - [Respiratory system involvement in pseudotuberculosis].
AB  - Clinical, microbiological, x-ray and immunological examinations of 1376 patients
      with pseudotuberculosis and 465 patients with acute respiratory diseases of viral
      or coccal origin, the trends in annual morbidity for the above diseases followed
      up within 7 years in the populations where the patients were registered and
      experimental investigations on rabbits provided evidence for primarily
      generalized pattern of pseudotuberculosis infection and a direct relationship
      between pulmonary lesions in the animals and effective dose of the infectant,
      route of the infection. The patients had nonspecific (non-yersiniosis) lesions of
      the respiratory system. Frequency of the infection was greater in cold seasons,
      especially in those who did not complete social and biological adaptation to new
      conditions, and depended on seasonal fluctuations of respiratory infection
      morbidity in nonrandom populations.

PMID- 8744114
TI  - [Mucociliary function in acute pneumonia].
AB  - Radioaerosol method was employed to follow up mucociliary transport (MT) efficacy
      in 97 patients with acute pneumonia (AP). The most pronounced suppression of MT
      was found in repeated and lingering AP. If causative agents were represented by
      adenoviruses, streptococci and influenza bacillus suppression of MT appeared more
      noticeable. Correlations of MT with pulmonary ventilation support the role of
      mucociliary insufficiency in genesis of bronchial obstruction in AP. The majority
      of the convalescents fail to achieve complete recovery of MT.

PMID- 8744115
TI  - [Pulmonary aspergillosis in patients with disseminated processes in the lungs].
AB  - Sera of 30 patients with disseminated processes in the lungs of various etiology
      were examined for the presence of specific IgG to antigens of Aspergillus
      fumigatus (A.f.) and Candida albicans (C.a.) using solid phase enzyme
      immunoassay. Elevated concentrations of IgG to A. f. and C. a. were found in 6
      and 12 patients, respectively. Serodiagnosis was confirmed by a direct detection
      of the fungi in the bronchi (cytology of the lavage, culturing). It is highly
      probable that opportunistic fungi may be involved in pulmonary dissemination.
      Therefore, patients with disseminated pulmonary diseases should be examined for
      opportunistic fungi.

PMID- 8744116
TI  - [Weight-reducing diet therapy in the combined treatment of pulmonary
      sarcoidosis].
AB  - We have studied the effect of therapeutic fasting in 76 patients with pulmonary
      sarcoidosis (28, 45 and 3 patients with stage I, II and III, respectively). Fifty
      two patients with PS stage I, II and minimal clinical symptoms received fasting
      alone. Twenty-four patients with PS stage II, III and frequent recurrences
      received combined treatment (fasting and oral corticosteroids). The efficacy of
      the treatment was evaluated by clinical symptoms, X-ray picture, pulmonary
      capillary blood flow and immunological parameters. We have found that therapeutic
      fasting reduced clinical symptoms in 85% of the patients, improved x-ray picture
      in 62% of the patients. Positive trend was also registered in immunological
      parameters. Therapeutic fasting produced maximal positive effect in patients with
      PS stage I, II and duration of the disease less than 1 year. Patients with PS
      stage II, III and the disease duration more than 1 year should be treated with
      fasting in combination with corticosteroids.

PMID- 8744117
TI  - [Modeling hepatitis A in monkeys (results and prospects)].

PMID- 8744118
TI  - [Effects of buspirone on the development of an experimental depressive syndrome
      in rats, caused by systemic administration of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)].

PMID- 8744119
TI  - [Features of endocrine function changes in hypertensive NISAG line rats after
      exposure to adrenaline].

PMID- 8744120
TI  - [Use of an alpha-tocopherol emulsion for antioxidant protection of ischemic and
      conserved kidneys].

PMID- 8744121
TI  - [Effect of interferon on the development of Parkinson's syndrome, caused by
      administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57Bl/6
      mice].

PMID- 8744122
TI  - [Effect of dimebone on coronary blood flow and myocardial contractibility].

PMID- 8744123
TI  - [Differences in immune response, phagocytosis and detoxifying properties due to
      effect of peptide and amino acid preparations].

PMID- 8744124
TI  - [Hemoprotective effect of perfluorodecalin].

PMID- 8744125
TI  - [Participation of cholesterol in hypochlorite-induced oxidation of cholesterol
      phosphatidylcholine liposomes].

PMID- 8744126
TI  - [Increase of nitric oxide production in rat organs in heat shock].

PMID- 8744127
TI  - [Mechanism of succinate oxidation in white rat liver].

PMID- 8744128
TI  - [Effect of amiridine on rat learning in a radial maze].

PMID- 8744129
TI  - [Effect of dioxidine and cyclophosphamide on lipid peroxidation and superoxide
      dismutase and catalase activity in C57Bl/6 and BALB/c mice].

PMID- 8744130
TI  - [Anti-ischemic activity of immobilized cytochrome C].

PMID- 8744131
TI  - [Effect of the tranquilizer mebicar on lipid metabolism and lipid peroxidation in
      a rat hypokinesic model].

PMID- 8744132
TI  - [Features of the antidepressive effect of O-beta-chloroethyl-para-N
      dimethylaminophenylphosphinylacetic acid (amfazide)].

PMID- 8744133
TI  - [Immunologic mechanisms for increasing radioresistance under the effect of
      cholinomimetics].

PMID- 8744134
TI  - [Radioprotective effect of cystamine and heparin in experiments on mice with
      varying tolerances].

PMID- 8744136
TI  - [Effect of minimal bactericidal dose of chlorhexidine and other antiseptics on
      Bacillus subtilis 720 ribosomes].

PMID- 8744135
TI  - [Detection of Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma
      urealiticum in diseases of the male and female reproductive system by using
      polymerase chain reaction].

PMID- 8744137
TI  - [Effect of radiation on the functional status of neuronal chromatin in mice
      exposed in the region of the Chernobyl atomic power plant].

PMID- 8744138
TI  - [Effect of a complex preparation of isoniazide on mononuclear cells in
      tuberculous granuloma].

PMID- 8744139
TI  - [Role of the paternal hormonal status in the thymus involution in the offspring].

PMID- 8744140
TI  - [Transcription in nerve cells and hepatocytes from rats with dissimilar narcotic
      resistance during early postnatal ontogenesis].

PMID- 8744142
TI  - [Drifting cascade-like slowly developing adaptation mechanism during action of
      extreme factors on the body].

PMID- 8744143
TI  - [Dynamics of fibronectin synthesis by human cultured fibroblasts].

PMID- 8744144
TI  - [Role of various hierarchical brain structures in psychoemotional stress].

PMID- 8744145
TI  - [Effect of litter size on rat brain development during the nursing period].

PMID- 8744146
TI  - [Ultrastructure and proliferation of Ehrlich carcinoma cells exposed to a
      continuous infrared laser].

PMID- 8744147
TI  - [Ultrastructural changes in liver of white mice, caused by isogenic F1+ and F1-
      strains of the plague pathogen, and correction of them with ceftriaxone].

PMID- 8744149
TI  - [Sanitizing effect of volatile isolates from the intact common Myrtle (Myrtus
      communis L.) plant in an interior location].

PMID- 8744148
TI  - [Sexual features of acetylcholinesterase activity distribution in the dorsal
      vagal nucleus of newborn rats].

PMID- 8744150
TI  - [An isohormone-inhibitor of biological activity of gonadotropin activity in
      Baltic salmon].

PMID- 8744151
TI  - [Use of electron microscopy to increase resolving ability and sensitivity of in
      situ hybridization].

PMID- 8744152
TI  - [Cytologic mechanisms that are the basis for the growth of mink diapausal
      blastocysts].

PMID- 8744153
TI  - [Effect of heterochronic parabiosis on liver microsomal enzyme oxidation].

PMID- 8744154
TI  - [Functional asymmetry of adrenal glands in (CBA x C57BL/6)F1 mice].

PMID- 8744155
TI  - [Karyotypic analysis of the Saccharomyces exiguus complex].

PMID- 8744156
TI  - [Induced sensitivity to odorants: a new phenomenon].

PMID- 8744157
TI  - [Change in biological availability of 137Cs in grassland ecosystems after the
      accident at Chernobyl Atomic Energy Station].

PMID- 8744158
TI  - [Protein synthesis inhibitors stimulate DNA synthesis in resting NIH 3T3 cells].

PMID- 8744159
TI  - [Ultrastructural organization of the hepatoid gland epithelium in Phillip's dik
      dik, Madoqua phillipsi, and Grant's gazelle (Artiodactyla, Bovidae].

PMID- 8744160
TI  - [Dynamics of biodiversity and ecosystems in radioactive pollution].

PMID- 8744161
TI  - ECG response of the human body subjected to vibrations.
AB  - In this paper, the ECG response of the human body subjected to vibrations is
      investigated. Measurements relied on recording the ECG and then computing the
      normalized difference of the ECG power spectrum density. Ten subjects aged 20-22
      years old were exposed for 15 min to vertical vibrations in the frequency range 5
      30 Hz. Results show either depression or elevation of the ST segment indicating
      heart muscle fatigue. The power spectrum density normalized difference also shows
      that the maximum difference takes place at 8 Hz vibrations frequency which is
      thought to be around the resonance frequency of the heart.

PMID- 8744162
TI  - Voluntary telemetry control of functional electrical stimulators.
AB  - With the assistance of crutches and functional electrical stimulation (FES) we
      are able to restore standing and simple gait in some spinal cord injured (SCI)
      patients. In the present rehabilitative systems the patient divides the gait
      cycle into 'stance' and 'swing' phase by using pushbuttons mounted in the handles
      of the crutches. These are then hard wired to the functional electrical
      stimulator. We present the development and evaluation of a surface mount
      technology based telemetry system that provides reliable and interference
      resistant wireless control of FES assisted walking. The system makes use of radio
      frequency carriers operating at a frequency of 40 MHz. Crutch pushbutton signals
      are coded and transferred from the transmitter placed in the crutch to the
      receiver which is firmly attached to the patient's waist and connected to the
      stimulator. The telemetry system was found to be of special importance for both
      complete and incomplete SCI subjects and is currently in use at the
      Rehabilitation Institute of the Republic of Slovenia.

PMID- 8744163
TI  - Optimization of patient radiation dose through development of specifications for
      purchase of X-ray equipment.
AB  - X-ray equipment characteristics and performance have an important influence on
      radiation doses to patients. In order that these factors can be taken into
      consideration when X-ray equipment is purchased, dose related requirements need
      to be included in specifications and additional dose information requested from
      manufacturers. Dose factors include techniques that directly reduce exposure; use
      of low attenuation materials; provision of flexibility in choice of exposure
      parameters; and availability of data for dose assessment. If a standard format
      can be developed, this should enable manufacturers to supply this information.
      Specifications for different types of X-ray equipment and lists of dose
      information to be requested from manufacturers have been prepared by the Scottish
      Radiation Protection Advisers' Group for use in hospitals throughout Scotland. It
      is hoped that this will allow patient dose to be taken into account when X-ray
      equipment is purchased.

PMID- 8744164
TI  - Field analysis of a tape helix with embedded bio-media for microwave
      hyperthermia.
AB  - A general field theory has been developed for the EM wave propagation on a tape
      helix with embedded bone, muscle, fat and skin co-axial biological layers in a
      multilayered dielectric environment. The electric and magnetic fields in every
      biological/dielectric layer is formulated in terms of complex modified Bessel
      functions and complex exponentials, i.e. in terms of complex radial and axial
      propagation constants for the azimuthally symmetric and higher order spatial
      harmonics. A complete dispersion relation is derived by substituting the field
      expressions into as many boundary conditions as there are unknown constants. The
      dispersion relation is numerically solved for the complex axial propagation
      constant and hence for the phase velocity and depth of penetration for n = 0 and
      1 modes propagating along three dielectric loaded tape helices of different
      dimensions at several spot frequencies within the range of 300 MHz to 3.00 GHz.
      The results for variations in normalized phase velocity and depth of penetration
      with frequency for these modes separately and for the combined mode are
      presented. The patterns of specific absorption rate (SAR) across the cross
      section of the dielectric loaded helices are also computed and presented. The
      variations with frequency, and cross-sectional dimension of the helix of the
      normalized phase velocity, axial depth and SAR across the cross-section of each
      of the helices are discussed for the modes considered. The theoretical results
      for the propagation constant obtained by using a tape helix model for the
      azimuthally symmetric mode propagating along a wire helix loaded with a phantom
      muscle sample of known dielectric constant are compared with experimental results
      and with those obtained theoretically employing a sheath helix model at 2.45 and
      2.55 GHz. The use of a helix for human limb hyperthermia is also discussed.

PMID- 8744165
TI  - The CT scan (or MRI) before ECT: a wonderful test has been overused.

PMID- 8744166
TI  - Serum prolactin, electrode placement, and the convulsive threshold during ECT.
AB  - This study examines the relationship of serum prolactin changes (delta PRL) to
      variations in electrode placement after controlling for differences in the
      convulsive threshold. Previous studies showing greater release of PRL with
      bilateral (BL) compared with right unilateral (RUL) electrode placement were
      conducted without knowledge of the convulsive threshold. Twenty-two patients each
      received threshold RUL, threshold BL, 2.25 times threshold RUL, and 2.25 times
      threshold BL ECT. Serum PRL was collected 5 min before and 15 min after each
      electroconvulsive therapy (ECT). The convulsive threshold was greater for BL than
      RUL electrode placement. delta PRL was greater with BL than RUL ECT at comparable
      relative stimulus intensities. delta PRL was not correlated with seizure duration
      or absolute stimulus dose.

PMID- 8744167
TI  - Medical students' attitudes toward electroconvulsive therapy: an Indian
      perspective.
AB  - A questionnaire addressing issues related to electroconvulsive therapy (ECT) was
      administered to 165 undergraduate medical students in an urban hospital in India.
      Of various sources, the mass media contributed most to the students' knowledge
      about and attitudes toward the treatment. Senior and junior students differed
      little in their knowledge and attitudes. Many students believed that ECT is cruel
      and barbaric and that it occasions pain to the patient; however, few considered
      that it compromises thinking and reasoning, that it causes brain damage, that it
      is misused, that it is used to punish violent or uncooperative patients, that it
      is outmoded, or that it should be banned. Many students thought that the use of
      ECT should be governed by law. Myths and concerns about ECT were identified in a
      subset of students who expressed reluctance to receive ECT if indicated for
      themselves. There is a need to improve undergraduate medical education on ECT.

PMID- 8744168
TI  - Atrial fibrillation, anticoagulation, and electroconvulsive therapy.
AB  - We describe our experience with six patients with atrial fibrillation (AF) during
      electroconvulsive therapy (ECT). In four, we observed episodic or persistent
      conversion of AF to normal sinus rhythm (NSR). Four patients, three with
      cardioversion and one without, received anticoagulation. In published case
      reports, ECT was successfully performed in three patients with AF without
      anticoagulation and in three patients with AF who received anticoagulation. In
      addition, 18 patients received ECT while taking concomitant anticoagulation
      therapy for reasons other than AF. Despite the potential risk of embolization
      with AF, we consider ECT may be safely administered to patients with AF. Because
      of the high incidence of conversion of AF to NSR, anticoagulation therapy with
      either warfarin or heparin is recommended.

PMID- 8744169
TI  - Dangerous hyperglycemia associated with electroconvulsive therapy.
AB  - The literature on the effect of electroconvulsive therapy (ECT) on diabetes
      mellitus remains controversial, with evidence of both amelioration and worsening
      of hyperglycemia. Both clinical reports and animal models suggest that a critical
      factor in glucose homeostasis may be whether or not the diabetes is insulin
      dependent. We present a case in which ECT was associated with extreme
      hyperglycemia in a patient without known preexisting diabetes. The patient
      subsequently required treatment with an oral hypoglycemic agent, and eventually
      needed insulin. The possibility of an unmasking or exacerbation of diabetic
      pathology during a course of ECT must be considered. Various mechanisms by which
      ECT may influence hyperglycemia are discussed.

PMID- 8744170
TI  - Steroid-induced depressive psychosis responsive to electroconvulsive therapy.
AB  - We report the case of a 15-year-old girl with acute lymphoblastic leukemia who
      developed a severe steroid-induced depression, which was rapidly responsive to
      ECT. This report adds to the growing body of literature supporting ECT as a safe
      and effective treatment of affective and psychotic disorders in children.

PMID- 8744171
TI  - Maintenance ECT in a patient with catatonic schizophrenia and tardive dyskinesia.
AB  - We describe a 44-year-old-man with a 14-year history of catatonic schizophrenia
      and a 2-year history of tardive dyskinesia. Because of the worsening course of
      his illness in recent months, characterized by resistance to antipsychotic drugs
      and 4 hospitalizations in 7 months with early relapses after inpatient
      electroconvulsive therapy (ECT), outpatient maintenance ECT was administered.
      Without receiving any psychotropic medication, the patient's functional capacity
      was enhanced and he required no hospitalization during a 9-month period of
      maintenance ECT.

PMID- 8744172
TI  - Use of ECT after brain injury.
AB  - Electroconvulsive therapy (ECT) was administered to a man with a history of a
      gunshot wound to the head with persisting skull defect and intracranial metallic
      foreign bodies. It appears that ECT is a safe and effective treatment for
      depression in this setting. Electrode placement is selected to avoid the skull
      defect and anticonvulsant therapy may be continued if the patient was previously
      receiving it.

PMID- 8744173
TI  - Neuroleptic-resistant schizophrenia treated with clozapine and ECT.
AB  - Despite advancement in psychopharmacology, treatment-resistant schizophrenia
      still poses a challenge to modern psychiatry. We present four patients with
      schizophrenia treated with clozapine and ECT. One patient who developed
      neuroleptic malignant syndrome (NMS) on conventional neuroleptics experienced no
      complications with this combination.

PMID- 8744174
TI  - Placement of an implantable venous access device for use in maintenance ECT.
AB  - Achieving intravenous (i.v.) access prior to electroconvulsive therapy (ECT) can
      be painful and time consuming. It may contribute to premature discontinuation of
      therapy. The authors report a novel method of ensuring i.v. access in a patient
      receiving maintenance ECT who developed an aversion to needle sticks. A Port-A
      Cath P.A.S. vascular access catheter, placed in her left forearm, has been used
      for > 30 treatments without complication.

PMID- 8744175
TI  - Discontinuation of antidepressant medications before ECT.

PMID- 8744176
TI  - A geometric method of measuring the left ventricular ejection fraction on gated
      Tc-99m sestamibi myocardial imaging.
AB  - Geometric measurements of the left ventricular diameters as used in biplane
      angiocardiography and echocardiography were applied to gated SPECT Tc-99m
      sestamibi myocardial scintigrams in order to calculate the left ventricular
      ejection fraction. These measurements take no longer than 5 minutes and require
      no additional computer software. In a review of 79 examinations, the left
      ventricular ejection fraction calculated using these measurements correlated well
      with the echocardiographically estimated ejection fraction (r = 0.78, P <
      0.0001). The technique is highly reproducible with an intraobserver correlation
      of r = 0.94 and interobserver correlation of r = 0.93.

PMID- 8744177
TI  - Comparison of supine versus prone tomographic myocardial imaging. Effect on false
      positive rate.
AB  - As in most other nuclear medicine facilities, tomographic myocardial imaging was
      started here with the patients in the supine position. However, previous planar
      imaging experience indicated a high number of false-positive results using the
      supine position for left lateral views of the myocardium. Evaluating the accuracy
      of supine position SPECT imaging was considered necessary. In 1991, 228
      myocardial imaging procedures were performed during a period of 3 months.
      Coronary arteriography followed within 3 months in 67 of these patients,
      permitting evaluation of the accuracy of the imaging procedure interpretations.
      These correlations revealed the accuracy of myocardial imaging to be only 73%.
      This was caused mainly by a rather large number of false-positive results (24%)
      occurring mostly in the inferior-posterior wall. A similar comparison was
      performed in 1992 after a change to prone position for routine tomographic
      myocardial imaging with 63 of 295 patients undergoing coronary arteriography.
      These data revealed an increase in the overall accuracy to 81% and a decrease in
      the false-positive results to 16%. The improvements were almost entirely in the
      inferior-posterior regions with no significant change in the false-positive
      results in the anterior wall. These findings provide convincing evidence that the
      prone position should be selected for tomographic myocardial imaging.

PMID- 8744178
TI  - Spontaneous coronary artery spasm documented in a young woman. A case report.
AB  - A 35-year-old woman with coronary risk factors presented with nonexertional
      atypical burning chest pain of 1 week's duration. A myocardial perfusion study
      with Tc-99m MIBI revealed a severe stress induced anteroseptal perfusion defect
      that completely reperfused on a subsequent resting Tc-99m MIBI study. Coronary
      angiography showed mild nonobstructive coronary artery disease. At the
      termination of the procedure, a spontaneous episode of burning chest pain
      occurred. Left main coronary artery reinjection of contrast revealed proximal
      diffuse left anterior descending coronary artery spasm. The patient was followed
      for 2 years with no further episodes of chest pain, while on calcium channel
      blocker medication. The phenomenon of vasospastic angina and the role of
      myocardial perfusion scintigraphy is discussed.

PMID- 8744179
TI  - Giant hepatic hemangioma studied with intravenous total body arteriography
      technique. A case report.
AB  - Hepatic hemangiomas are the most common benign tumors of the liver. They are
      usually single, small, and asymptomatic. However, giant hepatic hemangiomas have
      been reported in the past, usually detected as incidental findings. Radionuclide
      blood pool imaging studies are used to confirm the presence of a hemangioma. This
      report describes a case of a giant hepatic hemangioma detected using intravenous
      total-body arteriography, done as a part of radionuclide blood pool hemangioma
      study. This simple addition to the regular RBC blood pool hemangioma study helps
      to determine the size of the liver in the early arterial phase and shows obvious
      increased blood pool activity in the delayed phase. It is also useful in
      detecting lesions in other parts of the body when present.

PMID- 8744180
TI  - Serial occurrence of two types of postpartum thyroid disorders. Usefulness of Tc
      99m pertechnetate uptake.
AB  - A 32-year-old woman with a history of Graves' disease had an episode of
      thyrotoxicosis 2.5 months after her first childbirth. Because of low thyroidal
      uptake of Tc-99m pertechnetate, a diagnosis of postpartum painless thyroiditis
      was made and the patient was observed without medication. After the normalization
      of serum levels of thyroid hormones, a second wave of thyrotoxic symptoms
      emerged. This time, the Tc-99m uptake was slightly elevated and the patient was
      diagnosed to have a relapse of Graves' disease. This case underscores the
      previously reported notion that thyroidal uptake was indispensable to distinguish
      these two causes of postpartum thyrotoxicosis.

PMID- 8744181
TI  - Use of a water enema to facilitate localization of gastrointestinal hemorrhage
      during Tc-99m labeled RBC scintigraphy.
AB  - The authors report the use of a tap water enema to displace, and thereby
      localize, a site of colonic bleeding that had remained fixed in the left lower
      quadrant of the abdomen and could not be accurately localized. In similar cases,
      this maneuver may help to localize colonic bleeds in a timely fashion, avoiding
      protracted imaging and obviating the need for additional diagnostic testing.

PMID- 8744182
TI  - Massive pulmonary embolism without symptoms demonstrated by radionuclide imaging
      with thromboemboli in both main pulmonary arteries.
AB  - Massive pulmonary embolism is defined as an anatomic obstruction of 50% or more
      of the pulmonary artery. A reduction of at least 50% of the cross-sectional area
      of the pulmonary artery causes significant hemodynamic instability and marked
      hypoxia exhibiting syncope, apprehension, hypotension, diaphoresis, chest pain,
      altered mental status, and shortness of breath. A patient, who had no definite
      clinical signs and symptoms, was demonstrated to have massive pulmonary embolism
      by extensive mismatched ventilation-perfusion defects scintigraphically and
      confirmed as thromboemboli in the main pulmonary arteries on a standard CT of the
      thorax. The lack of clinical manifestations of massive pulmonary embolism might
      be related to the insidious onset and progressive formation of thromboembolism.
      The patient gradually adapted to and/or compensated for hemodynamic changes.

PMID- 8744183
TI  - Tc-99m sestamibi uptake in infiltrating ductal carcinoma of the breast in a male
      patient.
AB  - A 73-year-old man had an asymptomatic, slowly growing breast nodule. The
      mammographic appearance was highly suspicious of a malignancy, but the patient
      refused to undergo a biopsy. Because breast carcinoma has been previously
      described to accumulate Tc-99m MIBI in women, mammoscintigraphy was performed as
      a complementary examination. Uptake of the agent was noted.

PMID- 8744184
TI  - Quantitative lung perfusion scintigraphy in postoperative evaluation of
      congenital right ventricular outflow tract obstructive lesions.
AB  - Improved methods to relieve pulmonary artery stenosis have emphasized the need
      for an accurate noninvasive method to quantify the pulmonary blood flow. The aim
      of this study was to compare the roles of Tc-99m MAA perfusion lung imaging,
      chest x-ray, MRI, and cine-angiography for postoperative evaluation of pulmonary
      blood flow in patients with congenital right ventricular outflow tract (RVOT)
      obstructive lesions. Eleven patients underwent chest x-ray, MRI, perfusion lung
      imaging, and cine-angiography after corrective surgery of RVOT obstruction. The
      perfusion ratio on lung scans was calculated on the posterior views. The
      correlation coefficient of the left to right perfusion ratio measured by lung
      scans obtained with that by visual assessment of chest x-rays, with the most
      stenotic diameter ratio on MRI and on angiography being 0.57, 0.88 (P < 0.001),
      and 0.87 (P < 0.001), respectively. Follow-up perfusion lung scans in seven
      patients, before and after pulmonary artery intervention showed significantly
      improved perfusion ratios (0.30 +/- 0.11 to 0.70 +/- 0.22; P < 0.001), which were
      concordant with the clinical findings. The authors conclude that the quantitative
      perfusion lung scan is the noninvasive method of choice for postoperative
      evaluation of the pulmonary artery in congenital RVOT obstruction.

PMID- 8744185
TI  - Apparent intrathoracic spleen associated with marked scoliosis.

PMID- 8744186
TI  - Acute suppurative epididymal orchitis.

PMID- 8744187
TI  - Imaging of a giant Meckel's diverticulum in a young adult.

PMID- 8744188
TI  - Whole-body bone scan findings in X-linked hypophosphatemia.

PMID- 8744189
TI  - Soft-tissue tumor demonstrated on radionuclide venogram.

PMID- 8744190
TI  - Incidental detection of arterial aneurysms with Tc-99m human serum albumin.

PMID- 8744191
TI  - Tc-99m tetrofosmin lymph node uptake in myocardial perfusion imaging.

PMID- 8744192
TI  - Imaging of a mediastinal thymic carcinoid tumor with radiolabeled somatostatin
      analogue.

PMID- 8744193
TI  - Extensive cutaneous sarcoidosis. Ga-67 imaging.

PMID- 8744194
TI  - SPECT imaging in a patient with monostotic rib fibrous dysplasia.

PMID- 8744195
TI  - Diffuse pancreatic Ga-67 uptake in pancreatitis with markedly elevated Ca 19-9
      tumor marker.

PMID- 8744196
TI  - Detection of pericardial effusion during Tc-99m MIBI parathyroid imaging in a
      patient with chronic renal failure.

PMID- 8744197
TI  - Urinary bladder herniation into the scrotum. Incidental demonstration on bone
      scintigraphy.

PMID- 8744198
TI  - Scintigraphic appearance of dilated marginal artery of Drummond.

PMID- 8744199
TI  - Occipital photopenia.

PMID- 8744200
TI  - Limitations of parathyroid imaging with Tc-99m/Ti-201 subtraction and
      early/delayed Tc-99m MIBI imaging.

PMID- 8744201
TI  - Urinoma in a renal transplant patient.

PMID- 8744202
TI  - Multiple pathologic fractures mimicking bone metastases in a patient with
      Cushing's syndrome.

PMID- 8744203
TI  - Soft-tissue uptake of Tc-99m DPD (dicarboxypropane diphosphonate) in amyloidosis.

PMID- 8744204
TI  - Current readings in nuclear medicine.

PMID- 8744205
TI  - Developing three-dimensional models of ion channel proteins.

PMID- 8744206
TI  - Structural and functional diversity of voltage-activated calcium channels.
AB  - Data gathered from the expression of cDNAs that encode the subunits of voltage
      dependent Ca2+ channels have demonstrated important structural and functional
      similarities among these channels. Despite these convergences, there are also
      significant differences in the nature and functional importance of subunit
      subunit and protein-Ca2+ channel interactions. There is evidence demonstrating
      that the functional differences between Ca2+ channel subtypes is due to several
      factors, including the expression of distinct alpha 1 subunit proteins, the
      selective association of structural subunits and modulatory proteins, and
      differences in posttranslational processing and cell regulation. We summarize
      several avenues of research that should provide significant clues about the
      structural features involved in the biophysical and functional diversity of
      voltage-dependent Ca2+ channels.

PMID- 8744207
TI  - The GABAA receptors. From subunits to diverse functions.

PMID- 8744208
TI  - Structure and regulation of the amiloride-sensitive epithelial sodium channel.

PMID- 8744209
TI  - VDAC, a channel in the outer mitochondrial membrane.

PMID- 8744210
TI  - Ion channels and membrane receptors in follicle-enclosed Xenopus oocytes.

PMID- 8744211
TI  - Calcium-activated potassium channels in adrenal chromaffin cells.
AB  - Rat chromaffin cells express an interesting diversity of Ca(2+)-dependent K+
      channels, including a voltage-independent, small-conductance, apamin-sensitive SK
      channel and two variants of voltage-dependent, large-conductance BK channels. The
      two BK channel variants are differentially segregated among chromaffin cells,
      such that BK current is completely inactivating in about 75-80% of rat chromaffin
      cells, while the remainder express a mix of inactivating and non-inactivating
      current or mostly non-inactivating BKs current. The single-channel conductance of
      BKi channels is identical to that of BKs channels. Although rates of current
      activation are similar in the two variants, the deactivation kinetics of the two
      channels also differ. Furthermore, BKi channels are somewhat less sensitive to
      scorpion toxins than BKs channels. The slow component of BKi channel deactivation
      may be an important determinant of the functional role of these channels. During
      blockade of SK current, cells with BKi current fire tonically during sustained
      depolarizing current injection, whereas cells with BKs current tend to fire only
      a few action potentials before becoming quiescent. The ability to repetitively
      fire requires functional BKi channels, since partial blockade of BKi channels by
      CTX makes a BKi cell behave much like a BKs cell. In contrast, the physiological
      significance of BKi inactivation may arise from the ability of secretagogue
      induced [Ca2+]i elevations to regulate the availability of BKi channels during
      subsequent action potentials (Herrington et al., 1995). By reducing the number of
      BK channels available for repolarization, the time course of action potentials
      may be prolonged. This possibility remains to be tested directly. These results
      raise a number of interesting questions pertinent to the control of secretion in
      rat adrenal chromaffin cells. An interesting hypothesis is that cells with a
      particular kind of BK current may reflect particular subpopulations of chromaffin
      cells. These subpopulations might differ either in the nature of the material
      secreted from the cell (e.g., Douglass and Poisner, 1965) or in the
      responsiveness to particular secretagogues. The differences in electrical
      behavior between cells with BKi and BKs current suggest that the pattern of
      secretion that might be elicited by a single type of stimulus could differ. For
      BKi cells, secretion may occur in a tonic fashion during sustained
      depolarization, while secretion from cells with BKs current may be more phasic.
      In the absence of specific structural information about the domains responsible
      for inactivation of BKi channels, our understanding of the mechanism of
      inactivation remains indirect. BKi inactivation shares many features with N
      terminal inactivation of voltage-dependent K+ channels. However, there are
      provocative differences between the two types of inactivation which require us to
      propose that the native inactivation domain of BKi channels may occlude access of
      permeant ions to the BK channel permeation pathway in a position at some distance
      from the actual mouth of the channel. Further understanding of the structural and
      mechanistic basis of inactivation of BKi channels promises to provide new
      insights into both the cytoplasmic topology of BK channels and the Ca(2+)- and
      voltage-dependent steps involved in channel activation.

PMID- 8744212
TI  - Regulation of calcium release channel in sarcoplasmic reticulum.
AB  - In this review, we summarized the results obtained mainly by flux measurements
      through Ca2+ channel in HSR vesicles. The Ca2+ channel has a large pore which
      passes not only divalent cations such as Ca2+, Mg2+, and Ba2+ and monovalent
      cations such as Na+, K+, and Cs+, but also large ions such as choline and tris.
      The permeation rates of choline and glucose through the Ca2+ channel were
      measured quantitatively by the light scattering method. The slow permeation of
      such molecules may reflect the structure of pores since the permeation process is
      the rate-limiting step for such large molecules. Neutral molecules such as
      glucose became permeable in the presence of submolar KCl, which suggests that
      pore size of the channel becomes larger in KCl. The apparent permeation rates of
      Ca2+ and Mg2+ obtained from the flux measurement were the same, although their
      single-channel conductances were different. This discrepancy was explained by the
      fact that flux measurements reflects the open rate of the channel. Thus,
      complementarity between the flux measurement and single-channel recording was
      demonstrated. From the effects of K+ on the action of regulators on Ca2+ channel,
      it was suggested that the Ca2+ channel has many binding sites for activators and
      inhibitors. There are two kinds of Ca2+ binding sites for activation and
      inhibition. Activation sites for Ca2+, caffeine, and ATP are different and
      inhibition sites for Ca2+ and procaine are different. The binding sites for
      ruthenium red and Mg2+ are the same as the activation and/or inhibition sites for
      Ca2+. Ryanodine-treated Ca2+ channel became permeable to glucose even in the
      absence of KCl. The conformational state of the channel opened by ryanodine is
      different from that opened by Ca2+, caffeine, and ATP. The maximal flux rates of
      choline and glucose induced by ryanodine were smaller than those attained by
      caffeine and ATP. This result is consistent with the observation obtained by
      single-channel recording; the maximal value of single-channel conductance after
      ryanodine treatment becomes 40-50% of the value before the treatment. It is
      likely that the radius of the pore opened by ryanodine is smaller than that
      opened by Ca2+, caffeine, or ATP. The flexibility of the channel may be decreased
      in the open locked state induced by ryanodine. The Ca2+ response to open the
      channel by micromolar Ca2+ was lost when calsequestrin was released from the
      vesicles. It is possible that calsequestrin acts as an endogenous regulator of
      Ca2+ channel through triadin in excitation-contraction coupling.

PMID- 8744213
TI  - Single-channel studies in molluscan neurons.

PMID- 8744214
TI  - Neuronal nicotinic acetylcholine receptors.

PMID- 8744215
TI  - Determination of pantothenic acid in infant milk formulas by high performance
      liquid chromatography.
AB  - A reverse-phase liquid chromatographic method was adapted for the assay of
      pantothenic acid in infant milk formulas. Sample preparation consisted of
      deproteination with acetic acid and sodium acetate solutions, followed by
      centrifugation and filtration. The chromatographic system included a C-18 column
      and a mobile phase consisting of a sodium phosphate buffer and acetonitrile
      (97:3, vol/vol). The column effluent was monitored by UV detection at 197 nm. The
      system was linear from 50 to 800 ng. The recoveries of pantothenic acid from
      augmented samples ranged from 89 to 98%, and the coefficients of variation ranged
      from 1.17 to 3.20%. The results obtained with the HPLC and a microbiological
      method were highly correlated for starting infant formula, follow-up infant
      formula, and formula for infants of low birth weight from four different
      manufactures. All formulas analyzed contained pantothenic acid at concentrations
      higher than those declared on their nutritional labels and were in compliance
      with international recommendations.

PMID- 8744216
TI  - Effects of oocyte maturation length, sperm capacitation time, and heparin on
      bovine embryo development.
AB  - This study examined the effects of extending oocyte maturation 4 h beyond current
      methods and capacitating sperm with or without heparin 4 h before oocyte
      introduction to determine whether embryo development would increase after in
      vitro fertilization. Oocytes were aspirated from ovaries that were collected at
      slaughter. Cumulus-enclosed oocytes were matured in M-199 supplemented with serum
      from cows in standing estrus (20%), antibiotic-antimycotic solution (1%), HEPES
      (10 mM), and equine LH (30 micrograms/ml) in a humidified 5% CO2 atmosphere.
      Oocytes were matured for either 24 or 28 h and subsequently fertilized with sperm
      that had been capacitated 0 or 4 h (before oocyte contact) with or without
      heparin (0.2 microgram/ml). Data were analyzed as a 2 x 2 x 2 factorial design.
      Percentages of cleavage and development were transformed by the arcsin square
      root method before analysis of variance. An interaction of maturation length and
      sperm capacitation resulted because cleavage rate decreased with precapacitated
      sperm, but only within the 24-h maturation period. Heparin increased cleavage
      rate at 48 h after fertilization but did not affect further development. More
      oocytes developed to morulae when they matured for 24 h than when they matured
      for 28 h. In conclusion, a 24-h maturation length without precapacitated sperm
      was optimal for the subsequent development of cumulus-oocyte complexes.

PMID- 8744217
TI  - Effects of media, serum, oviductal cells, and hormones during maturation on
      bovine embryo development in vitro.
AB  - Our objective was to optimize in vitro maturation conditions of bovine oocytes as
      assessed by embryo development. In Experiment 1, cumulus-oocyte complexes were
      matured in either M-199 or RPMI-1640. Each medium was supplemented with an
      antibiotic-antimycotic solution (1%) and estrous cow serum (20%). Cumulus cell
      expansion after 24 h was greatest for cumulus-oocyte complexes matured in RPMI
      1640. Morulae development on d 7 was greater (21.1%) for oocytes matured in M-199
      than for oocytes that matured in RPMI-1640 (9.6%). In Experiment 2, cumulus
      oocyte complexes were matured in M-199 supplemented with antibiotic-antimycotic
      solution (1%). Main effects were serum type (20%; estrous cow serum vs.
      superstimulated estrous cow serum) and coculture (with or without bovine
      oviductal epithelial cells). The percentage of oocytes developing into
      blastocysts (d 9) was higher for oocytes matured in estrous cow serum regardless
      of coculture. In Experiment 3, effects of estradiol-17 beta (0, 1, and 2
      micrograms/ml) and equine LH (0, 10, 20, and 30 micrograms/ml) on cumulus cell
      expansion and development after fertilization were determined. Cumulus cell
      expansion and blastocyst development decreased with estradiol-17 beta in the
      maturation medium, but LH in the medium enhanced expansion of cumulus cells and
      blastocyst development.

PMID- 8744218
TI  - An improved method for the routine biopsy of bovine mammary tissue.
AB  - Eight primiparous cows in midlactation were used to determine a method for the
      mammary biopsy of standing cows in full lactation. Cows were mildly sedated;
      therefore, preoperative feed withdrawal was not necessary. A core of secretory
      tissue (0.75 to 1 g) was extracted using a rotating stainless steel cannula with
      a retractable blade at the cutting edge. Postoperative recovery was rapid, taking
      only 15 min per cow, and the method was reliable and efficient. The presence of
      secretory tissue was verified by histology and in situ hybridization with alpha
      s1-casein and alpha-lactalbumin probes. The capsular end of the core contained
      more connective tissue, and the parenchyma showed heterogeneous expression of
      alpha s1-casein and alpha-lactalbumin. Despite some postoperative bleeding, milk
      yield and composition in the biopsied gland were affected only transiently. Yield
      recovered by 3.5 d after biopsy, and composition recovered by 6.5 d after biopsy.
      Yield and composition of milk from the control glands were not affected by the
      procedure. Biopsy sites healed rapidly and without infection. No clinical
      mastitis was observed in any of the biopsied cows throughout the remainder of the
      lactation.

PMID- 8744219
TI  - Hexose phosphorylation by the ruminal bacterium Selenomonas ruminantium.
AB  - Three strains of Selenomonas ruminantium (D, GA192, and H18) were surveyed for
      phosphorylation of D-glucose and 2-deoxyglucose by phosphoenolpyruvate and ATP.
      Cells of all three strains that had been treated with toluene had high rates of
      hexose phosphorylation with either phosphoryl donor; this activity was
      constitutive in strain D. Glucose phosphorylation that was dependent on
      phosphoenolpyruvate was maximal at pH 7.2, remained fairly high at pH 6.5, but
      decreased (> or = 65%) at pH 5.0 for all strains. Cell extracts were used to
      evaluate the involvement of soluble kinases in 2-deoxyglucose phosphorylation.
      Both glucose and 2-deoxyglucose were phosphorylated by ATP, but phosphorylation
      of either hexose was negligible with phosphoenolpyruvate in each bacterium.
      Because phosphoenolpyruvate could not serve as a phosphoryl donor, the activity
      dependent on phosphoenolpyruvate in cells treated with toluene might have been
      due to a phosphotransferase system associated with the membrane. Unlabeled 2
      deoxyglucose was a strong inhibitor (> or = 59%) of [14C]glucose phosphorylation
      with ATP by cell extracts of all S. ruminantium strains, and unlabeled glucose
      was a strong inhibitor (> or = 78%) of [14C]2-deoxyglucose phosphorylation with
      ATP. Based on Lineweaver-Burk kinetics, 2-deoxyglucose was a competitive
      inhibitor of initial rates of kinase activity in strains D, GA192, and H18. These
      results collectively suggest that glucose phosphorylation with
      phosphoenolpyruvate and 2-deoxyglucose phosphorylation with ATP are common traits
      in these strains of S. ruminantium.

PMID- 8744220
TI  - Lasalocid and particle size of corn grain for dairy cows in early lactation. 1.
      Effect on performance, serum metabolites, and nutrient digestibility.
AB  - The effects were examined of corn grain particle size and the ionophore lasalocid
      on performance, blood parameters, and nutrient digestibility of early lactation
      cows. Smaller corn particle size was expected to result in faster rate of
      digestion and ruminal fermentation of starch. Eight multiparous and 4 primiparous
      cows in early lactation were fed diets (44% forage) with cracked or ground, dried
      shelled corn grain and with or without lasalocid (360.mg/d per cow). The
      experiment was a replicated (n = 3) 4 x 4 Latin square design with 21-d periods
      and a 2 x 2 factorial arrangement of treatments. Lasalocid tended to improve DMI.
      Lasalocid and ground corn decreased body condition loss and milk fat and
      increased milk protein. Ground corn tended to increase milk yield but had no
      effect on 4% FCM, lactose, and BW. For all cows, milk yield, 4% FCM, lactose, and
      BW were unaffected by lasalocid; however, subsequent analysis of individual
      squares revealed that milk yield of primiparous cows increased with lasalocid.
      Ground corn increased total tract starch digestibility and decreased NDF
      digestibility. Interactions between lasalocid and particle size of corn grain
      were observed only for change in serum insulin concentration before and after
      meals.

PMID- 8744221
TI  - Lasalocid and particle size of corn grain for dairy cows in early lactation. 2.
      Effect on ruminal measurements and feeding behavior.
AB  - The effects particle size of corn grain and the ionophore lasalocid on ruminal
      fermentation and feeding behavior of early lactation cows were examined. Eight
      multiparous and 4 primiparous cows in early lactation were fed diets (44% forage)
      with cracked or ground dried shelled corn grain and with or without lasalocid
      (360 mg/d per cow). The experiment was a replicated (n = 3) 4 x 4 Latin square
      design with 21-d periods and a 2 x 2 factorial arrangement of treatments. Ground
      corn decreased ruminal turnover time of starch, did not affect ruminal lactate
      concentrations, increased propionate, decreased the ratio of acetate to
      propionate, and decreased branched-chain fatty acids. The range of ruminal pH
      within a day increased with ground corn, but mean pH was unaffected by treatment.
      Lasalocid increased lactate concentrations and did not affect the ratio of
      acetate to propionate. Lasalocid increased total time spent ruminating, and
      ground corn decreased ruminal contractions. Lasalocid tended to increase water
      intake, and ground corn increased water intake. Interactions of lasalocid and
      particle size of the corn grain were observed for ruminal turnover time of starch
      and NDF, and ruminal pool size of acetate and total VFA.

PMID- 8744222
TI  - Fatty acid digestion in lactating dairy cows fed fats varying in degree of
      saturation and different fiber sources.
AB  - Six cannulated cows were assigned to six treatments in a 6 x 6 Latin square
      design to evaluate the effects of fat saturation and amount and source of
      effective fiber on fatty acid metabolism. Cows were fed a control diet with no
      added fat or diets with 5% added fat from saturated tallow, tallow, or animal
      vegetable fat; the diets with animal-vegetable fat had three percentages of
      effective fiber: 40% forage, 40% forage plus 20% soyhulls, or 60% forage. Cows
      fed diets supplemented with fat tended to have more disappearance of total fatty
      acids in the rumen than did those fed the control diet. Disappearance of fatty
      acids from the rumen, especially C16 and C18, was higher for cows fed the low
      fiber diet. The apparent digestibility of fatty acids in the small intestine was
      higher for cows fed the control diet than for those fed supplemental fat.
      Apparent digestibility also was reduced as fat saturation increased, primarily
      because of saturated tallow. Digestibility of C18:1 in saturated tallow was
      reduced, apparently in association with other saturated fatty acids. Fiber source
      had no effects on apparent intestinal digestibility of fatty acids.
      Concentrations of C18:0 and C18:1 in milk fat increased as the degree of fat
      saturation decreased, reflecting higher unsaturated C18 intake and ruminal
      biohydrogenation of polyunsaturated C18 fatty acids.

PMID- 8744223
TI  - Butylsoyamide increases unsaturation of fatty acids in plasma and milk of
      lactating dairy cows.
AB  - This study was designed to determine whether dietary butylsoyamide increased
      unsaturation of fatty acids in milk of lactating dairy cows. Nine Holstein cows
      were fed three diets in a 3 x 3 Latin square design, replicated three times. One
      diet was a control with no added fat, and the other two diets were supplemented
      (3.5% of the DM) with either soybean oil or butylsoyamide. Milk yields and DMI
      were similar for the three diets. Milk fat percentage and FCM were reduced by
      soybean oil, but not by butylsoyamide. Milk protein yield was reduced when
      butylsoyamide was fed, and milk fat yield was reduced when soybean oil was fed.
      The soybean oil supplement disrupted ruminal fermentation, causing total VFA and
      acetate concentrations to decline; the butylsoyamide supplement had no effect on
      ruminal VFA. The proportion of linoleic acid in plasma fatty acids was similar
      with the control (54.3%) and soybean oil (52.0%) diets but was higher with
      butylsoyamide (59.0%). Linoleic acid concentration in milk fat averaged 3.60,
      4.77, and 6.28% for the control, soybean oil, and butylsoyamide diets,
      respectively. Conversion of soybean oil to butylsoyamide protected unsaturated
      fatty acids from ruminal biohydrogenation, causing linoleic acid to increase in
      the plasma and milk of dairy cows.

PMID- 8744224
TI  - Dose response of dairy cows to abomasal administration of four amounts of L
      carnitine.
AB  - Four Holstein cows were used in a 4 x 4 Latin square design with 21-d periods to
      determine the response to increasing amounts of L-carnitine infused into the
      abomasum. During d 1 to 7 of each period, cows were abomasally infused with 4 L/d
      of water; during the remainder of each period, 0, 3, 6, or 12 g/d of carnitine
      dissolved in 4 L of water were infused continuously into the abomasum. The DMI,
      milk yield, and milk composition were not affected by carnitine infusion.
      Apparent digestibilities of DM, OM, CP, ADF, NDF, and energy decreased linearly,
      and fatty acid digestibility tended to decrease linearly, when up to 12 g/d of
      carnitine were infused. Balances of energy and N generally were unaffected by
      carnitine infusion. The concentrations of carnitine in plasma and urine increased
      linearly, and that in milk increased quadratically, as the amount of infused
      carnitine increased; the concentrations of carnitine in plasma and milk appeared
      to be maximized when 6 g/d of carnitine were infused. Total carnitine excreted
      and carnitine excretion above basal excretion increased linearly as amounts of
      infused carnitine increased; however, < or = 23% of the daily carnitine dosage
      was excreted above basal carnitine excretion. Infusion of up to 12 g/d of
      carnitine into the abomasum did not improve milk yield or nutrient
      digestibilities.

PMID- 8744225
TI  - The effect of dietary crude protein as protected soybean meal on mammary
      metabolism in the lactating dairy cow.
AB  - Metabolism in the mammary gland was related to changes in milk output in response
      to changes in dietary protein intake. Three diets of grass silage and concentrate
      were fed to four lactating dairy cows equipped with intravascular catheters
      across the mammary gland. Concentrates differed in the inclusion of protected
      soybean meal and provided 11.3, 15.4, and 20.1% CP, respectively. Blood samples
      were taken to assess the effect of protein percentage on the nutrient fluxes
      across the gland and their relationship to milk production. Milk production, milk
      protein yield, and milk protein concentration were all increased as CP intake
      increased, although these responses were not linear. Concentrations of urea in
      milk reflected those in plasma and increased as dietary protein intake increased.
      Uptake of glucose and BHBA by the mammary gland tended to increase as milk
      production increased. Arterial supply of essential AA increased as the dietary
      protein increased. Supply and uptake of nonessential AA were unchanged by dietary
      treatment, and uptake was insufficient to account for output of nonessential AA
      residues in milk protein. The supply of essential AA was not limiting for milk
      protein synthesis, and some alternative mechanism must have existed for the
      control of milk protein yield.

PMID- 8744226
TI  - In vitro ruminal degradation and synthesis of protein on fractions extracted from
      alfalfa hay and silage.
AB  - Net release of degraded N as NH3 and total AA plus microbial protein synthesis,
      quantified from incorporation of 15NH3 into microbial protein, was used to
      estimate the rate and extent of in vitro degradation of protein fractions
      isolated from alfalfa hay and silage. Seven proteins (casein, alfalfa hay,
      alfalfa silage, extracts from alfalfa hay and silage, and residues from alfalfa
      hay and silage) were studied. Results from (NH4)2SO4 and SDS-PAGE fractionations
      suggested that soluble proteins in alfalfa hay and silage differed in
      susceptibility to proteolytic attack. Although the net release of NH3 plus total
      AA N from alfalfa silage and alfalfa silage extract was twofold greater than that
      from alfalfa hay and alfalfa hay extract, net microbial protein synthesis on
      alfalfa hay and alfalfa hay extract was 33 and 43% greater. Despite greater NPN
      content in alfalfa silage, protein degradation rate and estimated escape were
      similar for intact alfalfa hay (0.103/h and 43%) and silage (0.067/h and 43%).
      This result might be explained by the less efficient microbial utilization of
      silage NPN, greater protozoal numbers on hay, greater soluble true protein in
      hay, or differences in molecular mass and stability of soluble proteins in hay
      versus silage. Use of a two-compartment model, based on water-soluble and
      insoluble CP fractions assumed to pass with the liquid and solid phases,
      respectively, yielded RUP estimates for alfalfa hay and silage that were similar
      to NRC estimates.

PMID- 8744227
TI  - Influence of source and amount of dietary protein on milk yield by cows in early
      lactation.
AB  - The purpose of this research was to examine the effects of various amounts of CP
      and RUP on AA flow to the small intestine and milk yield of lactating dairy cows.
      The first trial was a 5 x 5 Latin square design using five ruminally and
      duodenally cannulated multiparous cows. Diets contained chopped alfalfa hay, corn
      silage, high moisture corn, solvent-extracted soybean meal, and specially
      processed soybean meal (60.2% RUP). Soybean meal replaced high moisture corn to
      increase dietary CP from 14.5 to 16.5 or 18.5%, and specially processed soybean
      meal replaced solvent-extracted soybean meal in diets containing 16.5 or 18.5% CP
      to provide 6.2, 7.3, 6.7, and 8.3% RUP. Increasing dietary CP increased the flows
      of all AA to the duodenum. Increasing dietary RUP increased flows of Arg, His,
      Lys, Phe, Asp, and Glu to the duodenum. In a second trial, 36 cows were fed diets
      similar to those used in trial 1. Increased amounts of RUP in diets tended to
      increase milk yield because of improved protein status, improved intake of
      metabolizable energy, or both.

PMID- 8744228
TI  - Evaluation of a ruminally protected methionine product for lactating dairy cows.
AB  - In Experiment 1, three ruminally and duodenally cannulated cows were used to
      assess the extent of ruminal protection and postruminal release of Met from
      ruminally protected Met using a polyester bag technique. The ruminally protected
      Met contained 85.1% DL-Met (wt/wt). Ruminal disappearance of Met averaged 5.8,
      8.1, 21.8, 37.5, and 87.5% after 3, 6, 12, 24, and 96 h of incubation,
      respectively. Postruminal disappearance of Met from bags inserted in the duodenum
      after treatment with pepsin-HCl averaged 63.4, 62.6, 51.6, 43.6, and 8.8% for
      bags incubated in the rumen for 3, 6, 12, 24, and 96 h, respectively. In
      Experiment 2, 12 cows were fed either 0 or 20 g/d of ruminally protected Met from
      7 to 10 d prepartum until 18 wk postcalving. Cows were fed the same total mixed
      diet. The DMI; yields of milk, CP, and SNF; and percentages of fat, CP, and SNF
      in milk were not affected by treatment. However, yields of fat and 3.5% FCM
      increased when ruminally protected Met was fed. Milk N components were not
      affected by treatment. Concentrations of Met increased in plasma when ruminally
      protected Met was fed. The mechanism for the increased production of milk fat and
      3.5% FCM when ruminally protected Met was fed is unknown.

PMID- 8744229
TI  - Effects of supplemental shade on thermoregulatory response of calves to heat
      challenge in a hutch environment.
AB  - Holstein (n = 12) and Guernsey (n = 6) calves, housed in hutches, were used to
      evaluate the complex relationships among external environment, housing
      microclimate, and thermal status of calves. The study was conducted during the
      summer; 9 calves were housed in hutches under supplemental shade, and 9 calves
      were maintained in hutches under direct sunlight. Environmental and calf
      temperatures were measured twice daily at 0700 and 1500 h, which included
      determinations of air temperature, inner and outer surface temperatures of the
      hutch, rectal and skin temperatures of the calf, and respiration rate. Outer and
      inner surface temperatures of the hutch were lower under supplemental shade.
      Hutch air temperature was highly correlated with inner surface temperature and
      therefore was lower in the shaded environment. During the p.m. period, when heat
      stress was highest, calves housed in a shaded hutch environment had lower skin
      temperatures and respiration rates than did unshaded calves. Body temperature and
      respiration rates increased less for calves in shade than for calves in sun.
      These data define the relationship between the calf and the environment.
      Supplemental shade diminished the severity of heat stress experienced by calves
      that were housed in hutches during the summer.

PMID- 8744230
TI  - Relationships between polymorphism for mitochondrial deoxyribonucleic acid and
      yield traits of Holstein cows.
AB  - Two independent data files from the breeding herd of Iowa State University and
      six North Carolina herds were used to examine relationships between yield traits
      and mtDNA polymorphism. Maternal lineages were established by tracing ancestry of
      cows to founder females in the herd book of the Holstein Association. Data from
      Iowa State University were 1476 records from 602 cows from 29 maternal lineages.
      The nucleotides of mtDNA encoding rRNA were sequenced. Eleven sites of
      polymorphism were found. An animal model for gene substitution was used to
      examine the relationship between sequence differences and yield traits. Traits
      analyzed were mature equivalent yield of milk, fat, SNF, and milk energy as well
      as concentrations of fat, SNF, and milk energy. Effects of sequence differences
      were significant for most traits. Sequence information from the D-loop was
      available for 12 lineages from North Carolina. The effect of polymorphism at 4
      sites was examined using 1472 records from 668 cows. Traits measured were the
      same, except that protein replaced SNF. No significant relationships existed
      between any of the traits and D-loop polymorphism, but results suggested that an
      association might exist between polymorphism and concentrations of milk yield,
      fat percentage, and energy. Whenever a significant relationship was detected, the
      effect of mutation (rare genotype) was detrimental.

PMID- 8744231
TI  - Multiple herd evaluation of the effects of maternal lineage on yield traits of
      Holstein cattle.
AB  - Effects of maternal lineage on yield traits were examined by using animal models.
      Data were 6054 multiparous records of 2264 cows from six herds in North Carolina
      and the breeding herd of Iowa State University. Separate analyses were performed
      by using first lactation records from North Carolina, all records from North
      Carolina, and pooled records from North Carolina and Iowa. Traits were mature
      equivalent yields of milk, fat, and protein; percentages of fat and protein; and
      milk energy concentration and yield. Cattle were assigned to maternal lineages on
      the basis of the earliest female ancestor recorded. Fixed effects in the models
      were herd-year-season, parity, and maternal lineage; random effects were animal,
      permanent environment, and residual. All additive genetic relationships were
      considered. For all analyses, maternal lineage was associated with significant
      differences in fat percentage and milk energy concentration. Differences between
      maternal lineages for yield traits were not significant. Variance components were
      also obtained with REML using the same data and models, but with lineage as a
      random effect. Based on records pooled from Iowa and North Carolina, maternal
      lineage accounted for 2.7% of the variance in fat percentage. Otherwise, < 1.2%
      of the variance of any trait was associated with maternal lineage.

PMID- 8744232
TI  - Impacts of cytoplasmic inheritance on genetic evaluations.
AB  - Simulation was used to examine the consequences of ignoring cytoplasmic effects
      on genetic evaluations. Effects on variance component estimation, accuracy of
      selection, genetic trend, and selection of bull-dams were considered. Comparisons
      were made for sire and animal models, several levels of cytoplasmic variance, and
      definition of cytoplasmic effects as either fixed or random. Ten replications
      with approximately 9000 cows and 20,000 records were simulated for each model and
      level of cytoplasmic variance. Derivative-free REML was used for estimation of
      variance components. Ignoring cytoplasmic effects caused overestimation of
      heritability with an animal model. Permanent environmental variance was
      underestimated with an animal model and overestimated with a sire model. Results
      were used for simulation of large (approximately 200,000 cow) data files for
      analysis of effects on accuracy of selection. Accuracy of selection increased
      when cytoplasmic effects were accounted for properly. Improvement of predicted
      breeding values was greater for cows than for sires and increased as cytoplasmic
      variance increased. Genetic trend also increased slightly, primarily as a
      function of increased accuracy of bull-dam selection. Little practical difference
      was detected when cytoplasmic effects were considered to be fixed rather than
      random.

PMID- 8744233
TI  - Misidentification rate in the Israeli dairy cattle population and its
      implications for genetic improvement.
AB  - The DNA microsatellites can be efficiently used to determine incorrect paternity
      attribution of cattle without genotyping of dams. Allelic frequencies of the
      population were determined for 12 microsatellites using the maternal alleles of
      102 AI sires. The frequency of the most common microsatellite allele ranged from
      0.27 to 0.58. Most loci had at least one allele that was present in only a single
      individual. Paternity of 9 of 173 cows (5.2%) and 3 of 102 bulls (2.9%) was
      excluded because putative paternal alleles were not present in progeny for at
      least one locus. For 4 of the 9 cows and all 3 bulls, exclusion was based on at
      least two loci. Mean probability of exclusion was 0.85 for cows and 0.99 for
      bulls. With an assumed cost of US $5 per genotype, a misidentification rate of
      5%, and a discount rate of 0.05, additional profit for the Israeli-Holstein
      breeding program from genotyping 100 test daughters of each young sire becomes
      positive within 10 yr and reaches nearly US $2.4 million after 20 yr.

PMID- 8744234
TI  - Effect of selection for milk yield and dietary energy on yield traits, bovine
      somatotropin, and plasma urea nitrogen in dairy cows.
AB  - Effects of genetic merit on energy intake, milk yield, fat and protein
      percentages, BW, BW change, plasma concentration of bST, and plasma concentration
      of urea N were determined for 139 heifers. Heifers, daughters of bulls of high
      genetic merit (average +408 kg of PTA for milk) or of average genetic merit
      (average -153 kg of PTA for milk), were allotted to either a high or low energy
      diet. Heifers of high genetic merit yielded 8.1% more milk and had 7.7% higher
      bST concentration than did heifers of average genetic merit, which were 3%
      heavier than heifers of high genetic merit. There was no significant effect of
      genetic merit group on energy intake, plasma concentration of urea N, or
      percentages of fat and protein. Heifers fed the high energy diet consumed 35.1%
      more energy, yielded 11.8% more milk with a lower fat percentage, and weighed 3%
      more than did heifers fed the low energy diet. The high energy diet depressed bST
      concentration by 13.3% and plasma concentration of urea N by 14.2% compared with
      concentrations for heifers fed the low energy diet. Correlations among bST, BW,
      and energy intake were negative and significant. Correlations of bST
      concentration with milk yield, fat percentage, and protein percentage were not
      significant. Body weight, BW change, milk yield, and energy intake were
      negatively correlated with plasma concentration of urea N.

PMID- 8744235
TI  - Phenotypic relationship of yield and type scores from first lactation with herd
      life and profitability.
AB  - Milk records from Ayrshire, Brown Swiss, Guernsey, Jersey, and Milking Shorthorn
      cows that first calved between 18 and 35 mo were combined with scores for linear
      type traits collected before 43 mo during first lactation to study herd life and
      lifetime profitability. Profitability (discounted relative net income) was the
      value of milk, calves, and cow salvage minus fixed costs, operating costs, and
      cow depreciation costs. Cows were included if they appeared only in a single herd
      and if the herd remained on test for 72 mo after birth date of the cow.
      Phenotypic correlations were computed for milk and fat yields and for 14 type
      traits during first lactation with nine variables for lifetime performance from
      3895 Ayrshire, 7997 Brown Swiss, 20,179 Guernsey, 71,731 Jersey, and 628 Milking
      Shorthorn cows. Multiple correlations for predicting discounted relative net
      income for the four breeds with the most data were 0.43 to 0.46 from milk and fat
      yields (linear and quadratic effects) during first lactation, 0.11 to 0.29 from
      final score, and 0.21 to 0.33 from all type traits. Type scores had considerably
      less predictive ability than yield during first lactation for predicting
      profitability and had limited predictability after yield was included. Final
      score increased multiple correlations only 0.00 to 0.02 above that for yield for
      the same four breeds. Final score plus 13 type traits (linear, quadratic, and
      interaction effects) increased multiple correlations only 0.02 to 0.04 above that
      for yield. Because of the limited value of some of the linear type traits, an
      effort should be initiated to eliminate them from programs of breed associations.

PMID- 8744236
TI  - Effects of days dry, previous days open, and current days open on milk yields of
      cows in Zimbabwe and North Carolina.
AB  - Effects of days dry and previous and current days open on milk yields during the
      first three lactations were determined for Holsteins from Zimbabwe and North
      Carolina. The animal models used included animal; permanent environmental effects
      of cows for herd-year, month of calving, age, current days open, and DIM; and the
      inverse of additive numerator genetic relationships. Model 1 for first lactations
      included only these effects, but Model 2, the animal model for later lactations,
      included these effects plus previous days open, previous days dry, and previous
      milk yield. The dependent variable in both models was unadjusted milk yield for
      the lactation. Current and previous days open, previous days dry, and DIM were
      also fitted as dependent variables with Models 1 and 2, except for previous milk
      yield, when appropriate. As current days open increased, milk yield rose,
      regardless of milk yield during prior lactations. Milk yields were reduced for
      lactations following < 60 d dry and showed little advantage for longer dry
      periods. The effects of previous days open are real but are overestimated unless
      permanent environmental effects of cows are considered simultaneously. The
      heritabilities and repeatabilities of current and previous days open and previous
      days dry were higher for cows in Zimbabwe than for those in North Carolina.
      Results suggest that, to obtain unbiased estimates of breeding values of sires
      and cows, yield data should be adjusted for the environmental effects of days dry
      as well as those of previous and current days open.

PMID- 8744237
TI  - Photoperiod and temperature interact to affect immune parameters in adult male
      deer mice (Peromyscus maniculatus).
AB  - Nontropical rodents often experience large seasonal fluctuations in both food
      availability and energy demands. The energy required for thermoregulation is
      highest during the winter when food availability may be at an annual minimum.
      Failure to cope with winter probably accounts, in part, for the increased
      prevalence of disease and death relative to that in summer. Winter conditions may
      elevate circulating glucocorticosteroid levels, which can compromise immune
      function. To increase the odds of surviving the energetic demands of winter,
      individuals of some rodent species appear to enhance immune function before
      conditions deteriorate. Previous laboratory studies suggest that immune
      enhancement can be induced by short days. These findings contrast with the
      results of several field studies reporting suppressed immune function during the
      winter. To resolve this conflict, the authors hypothesized that winter stressors
      present in field studies counteracted the short-day enhancement of immune
      function reported in laboratory studies. If true, then immune function of captive
      mice in short days should be compromised by low temperature or reduced food
      availability. Both ambient temperature and photoperiod were manipulated in the
      present study to assess their effects on immune parameters in male deer mice
      (Peromyscus maniculatus). Animals in short days regressed their reproductive
      systems and also displayed significantly higher immunoglobulin G (IgG) levels
      than did those in long days. Deer mice maintained in low temperatures had
      significantly reduced splenic masses and basal IgG levels independent of day
      length. Animals maintained in both short days and low temperatures displayed IgG
      levels comparable to those of mice in long-day/mild-temperature conditions.
      Animals maintained in long days and low temperatures had significantly higher
      serum corticosterone levels than did animals maintained in long days at mild
      temperatures. These data are consistent with the hypothesis that immune
      parameters are enhanced in short days to counteract stress-mediated immune
      suppression occurring during the winter.

PMID- 8744238
TI  - Chemical and behavioral stimulation from females accelerates recrudescence in
      male Syrian hamsters exposed to short days.
AB  - Interaction with female hamsters maintained under long photoperiods (LP)
      accelerates behavioral recrudescence in short photoperiod (SP) males. In this
      experiment, the authors investigated the effects of various types of female
      sociosexual cues on different measures of reproductive recrudescence in the male.
      Five groups of SP males were exposed to different female cues for 3 weeks (Weeks
      12 to 15). At Week 16, males were allowed to interact with estrus females;
      behavioral, physiological, and fecundity measures were monitored. The results
      show that all measures responded in a pseudo-dose-dependent manner to the
      different female cues presented. SP males not exposed to any female cues and
      those exposed to distal visual, auditory, and volatile pheromonal cues from
      estrus females did not copulate, deposit sperm, or impregnate estrus females
      presented to them at Week 16. SP males allowed direct access to the bedding of
      estrus females showed marked improvements on these same reproductive measures by
      Week 16. However, SP males that interacted with LP females between Weeks 12 and
      15 showed the greatest level of reproductive function at Week 16. These results
      show that the type of female sociosexual stimulation is important in accelerating
      reproductive recrudescence; whereas interaction with LP females may be important
      in accelerating behavioral recrudescence, both interaction with and exposure to
      the bedding of LP females may be important in accelerating physiological and
      reproductive success measures.

PMID- 8744239
TI  - Melatonin and light induce phase shifts of circadian activity rhythms in the
      C3H/HeN mouse.
AB  - This study examines the effect of light pulses and administration of the pineal
      hormone melatonin on the circadian activity rhythm of C3H/HeN mice. Mice were
      housed in constant dark in cages equipped with running wheels. Phase shifts in
      the circadian rhythm of wheel-running activity were measured following treatment
      with a 15-min pulse of light (300 lux) or administration of vehicle
      (ethanol/saline) or melatonin (90 micrograms, sc). Light treatment induced phase
      changes in circadian activity rhythms; specifically, delays during early
      subjective night (circadian time [CT] 12.5 to CT 18.5) and advances during late
      subjective night (CT 0.5). A single dose of melatonin administered at various CTs
      had no consistent effect on free-running circadian activity rhythms. By contrast,
      melatonin administration for 3 consecutive days at the same clock time induced
      advances in circadian activity rhythms by more than 1 h when the first dose was
      administered at CT 10 and induced delays in circadian activity rhythms by up to 1
      h when the first dose was administered between CT 24 and CT 2. With the caveat
      that multi- ple melatonin treatments are required to induce phase shifts, the
      results suggest that the circadian timing system controlling the rhythm of wheel
      running activity in the C3H/HeN mouse is responsive to both light and melatonin.

PMID- 8744240
TI  - Temperature sensitivity of the suprachiasmatic nucleus of ground squirrels and
      rats in vitro.
AB  - Temperature compensation of circadian rhythms in neuronal firing rate was
      investigated in the suprachiasmatic nucleus (SCN) of ground squirrels and rats in
      vitro. A reduction in SCN temperature from 37 to 25 degrees C reduced peak firing
      rates by > 70% in rats but only by approximately 21% in squirrels; trough firing
      rates were marginally altered in both species. In the rat SCN at 25 degrees C,
      the peak in neuronal activity decreased progressively on successive days and
      circadian rhythms no longer were present by Day 3. There was a 37% reduction in
      the number of single units detected and an increase in the temporal variability
      of peak firing rates among individual rat SCN neurons at low temperature. By
      contrast, single units were readily detected and circadian rhythms were robust in
      squirrels at 37 and 25 degrees C; a Q10 of 0.927 was associated with a shortening
      of tau by 2 h and a 5-h phase change after only 48 h at low temperature. These
      results suggest that temperature can have a substantial impact on circadian
      organization in a mammalian pacemaker considered to be temperature compensated.

PMID- 8744241
TI  - Bicuculline increases and muscimol reduces the phase-delaying effects of light
      and VIP/PHI/GRP in the suprachiasmatic region.
AB  - The present study investigated the effects of gamma-amino butyric acid (GABA)A
      active drugs on the ability of light or coadministration of vasoactive intestinal
      peptide (VIP), peptide histidine isoleucine (PHI), and gastrin-releasing peptide
      (GRP) to phase delay hamster activity rhythms. Microinjection of the GABAA
      agonist, muscimol, significantly (p < .01) reduced the phase-delaying effect of
      light administered at circadian time (CT) 13.5. By contrast, microinjection of
      the GABAA antagonist, bicuculline, significantly (p < .01) increased the phase
      delaying effect of light administered at CT 13.5. Microinjection of muscimol or
      bicuculline into the suprachiasmatic nucleus (SCN) produced little or no effect
      on circadian phase when no light pulses were provided. Coadministration of
      muscimol with VIP/PHI/GRP significantly (p < .01) reduced the phase-delaying
      effect of VIP/PHI/GRP, whereas administration of bicuculline with VIP/PHI/GRP
      significantly (p < .05) increased the phase-delaying effect of these peptides.
      These data indicate that changes in GABAA activity within the SCN can modulate
      the phase-delaying effects of light and VIP/PHI/GRP during the early portion of
      subjective night.

PMID- 8744242
TI  - Regulation of the phase and period of circadian rhythms restored by
      suprachiasmatic transplants.
AB  - The influence of exogenous signals on circadian rhythms restored by transplants
      of the suprachiasmatic nucleus (SCN) of the hypothalamus has received little
      study. The authors tested the responsiveness of hamsters bearing SCN transplants
      to photic and pharmacological treatments. Light intensities as high as 6,500 lux
      were insufficient to produce entrainment, although masking was observed
      frequently. Triazolam failed to produce statistically significant phase shifts
      when administered during the subjective day, but 2 animals bearing functional SCN
      grafts responded to this benzodiazapine during the subjective night. The authors
      next tested the hypothesis that the host can retain circadian aftereffects that
      influence the period of the circadian system reconstituted by the graft. Intact
      hamsters were entrained to light:dark cycles of short (23.25-h) and long (25-h)
      period (T) for at least 3 months. Control hamsters released into constant
      darkness exhibited profound and long-lasting aftereffects of entrainment to T
      cycles. Hamsters that received SCN lesions after exposure to these T cycles and
      SCN grafts 3 weeks later exhibited marginal but statistically significant
      aftereffects that disappeared within 3 months. On subsequent transfer to constant
      light, tau lengthened by 0.25 +/- 0.6 h in hamsters with intact SCN (p < .05).
      Animals bearing SCN grafts continued to free run in constant light but differed
      from intact animals in that circadian period did not lengthen. Functional SCN
      grafts contained vasoactive intestinal polypeptide (VIP), neurophysin (NP), and
      cholecystokinin (CCK) immunoreactive (ir) cells. Inputs of neuropeptide Y-and
      serotonin-ir fibers from the host brain to grafted SCN peptide cell clusters were
      variable. Limited observations using retrograde and anterograde tracers do not
      support the existence of extensive input to the graft. Retinal input overlapped
      only rarely with clusters of VIP-ir, CCK-ir, or NP-ir cells. The authors conclude
      that the circadian system reinstated by SCN transplants is relatively impervious
      to photic influences that exert parametric and nonparametric influences in intact
      hamsters. The transient expression of aftereffects induced in the host before
      transplantation indicates that extra-SCN systems of the host can influence the
      period of the reconstituted circadian system to at least a limited degree.

PMID- 8744243
TI  - Restoration of circadian rhythmicity by transplants of SCN "micropunches".
AB  - Although it is widely accepted that the suprachiasmatic nuclei (SCN) of the
      hypothalamus serve as biological pacemakers regulating circadian rhythmicity, a
      number of studies suggest that some circadian rhythms may be controlled by extra
      SCN structures. Transplantation of fetal anterior hypothalamic tissue containing
      the SCN restores circadian locomotor rhythms in SCN-lesioned hosts. Such
      transplants, however, contain substantial extra-SCN hypothalamic tissue. In the
      present study, the authors examined the recovery of circadian locomotor rhythms
      in animals implanted with small grafts harvested by taking "micropunches" from
      vibratome-sectioned brain slices. Micropunches were taken from three areas of the
      hypothalamus known to receive retinal input: the SCN, the subparaventricular
      zone, and the supraoptic nucleus. The results indicate that transplants
      restricted to the SCN region are necessary and sufficient for restoration of
      circadian locomotor activity rhythms and that micropunches of tissues from other
      sources are ineffective.

PMID- 8744244
TI  - Glutamic acid decarboxylase message isoforms in human suprachiasmatic nucleus.
AB  - The rat suprachiasmatic nucleus (SCN) is comprised of neurons that contain gamma
      amino butyric acid (GABA) colocalized with one or more peptides. In the present
      study, the authors employed in situ hybridization histochemistry to determine
      whether the human SCN also contains GABA neurons using synthetic oligonucleotide
      probes complementary to sequences of two isoforms of the GABA-forming enzyme,
      glutamic acid decarboxylase (GAD), GAD65, and GAD67. Most, if not all, SCN
      neurons appear to express both GAD65 mRNA and GAD67 mRNA with the content of
      GAD67 greater than GAD65. Both isoforms also are expressed in some neurons of the
      anterior hypothalamic area, in small neurons of the paraventricular nucleus but
      not in the supraoptic nucleus. These data indicate that neurons in the human SCN,
      like those in rodents, use GABA as a neurotransmitter.

PMID- 8744245
TI  - Muscle compliance: implications for the control of movement.
AB  - We suggest in this review that compliant properties of the neuromuscular system
      influence and must be considered at every level of motor function. These
      properties emerge from the combined operation of many physiological mechanisms.
      At the behavioral level, no aspect of the compliant response can be attributed to
      muscles or reflexes alone. Furthermore, for all but the slowest movements, all
      three mechanical properties must be taken into account. Although we have
      considered only reactions to external forces and the implications for normal
      voluntary movements, there are many other areas of relevance that we have not
      discussed. In particular, clinically important problems such as the control of
      orthotic/prosthetic devices, functional electrical stimulation, and the effects
      on muscle tone of neuromuscular pathologies like Parkinsonism are all issues in
      which compliant behavior is either the cause of problems or must at least be well
      characterized to allow successful treatment. These are all issues worthy of
      further study.

PMID- 8744246
TI  - The slow component of oxygen uptake kinetics in humans.

PMID- 8744247
TI  - Physical activity and health-related quality of life.

PMID- 8744248
TI  - From motor unit to whole muscle properties during locomotor movements.
AB  - Over the last century, progress has been made in understanding the basic
      structure and function of muscle. The emphasis on muscle research has become
      increasingly focused at the molecular level, and startling advances have been
      made. Surprisingly, at the whole muscle level significant questions remain
      unanswered. The details of how muscles are actually used in locomotion are
      lacking. The foregoing sections have discussed some basic muscle properties and
      then reviewed instances in which they have been directly measured during
      locomotor movements. Although most of the basic functional properties of muscle
      are known, some simple questions such as what the preferred operating point is on
      the F-L and F-V curves remain unanswered. Design principles of muscle structure
      and their control by the CNS have yet to be illuminated. Most in vivo techniques
      to study muscle function are difficult to use. This precludes their use on all
      but a small number of specialized muscles. With the exception of photography and
      electromyography, at best a small number of muscles can be studied at a time. The
      technique of measuring some muscle properties in vivo and then duplicating the
      conditions in an isolated muscle for further measurements seems promising.
      Combinations of mathematical models and careful experimental verification will
      also be necessary.

PMID- 8744249
TI  - Do physical activity and physical fitness avert premature mortality?

PMID- 8744250
TI  - Force-sharing among synergistic muscles: theoretical considerations and
      experimental approaches.

PMID- 8744251
TI  - Effects of acute and chronic exercise on fat metabolism.
AB  - Fatty acids are an important source of energy for skeletal muscle contraction,
      particularly during exercise of mild-moderate intensity, prolonged duration, and
      in the fasting state. Plasma FFA transported from remote adipose tissue stores
      and triglycerides contained within skeletal muscle fibers are the major sources
      of these fatty acids. The relative contribution of each source is dependent on
      the mode, intensity, and duration of exercise and on training status. Plasma FFA
      oxidation is directly related to the rate of lipolysis in adiopose tissue. The
      most potent stimulants of the latter are the catecholamines, but a lower plasma
      insulin concentration during exercise also plays a contributory role. In
      contrast, intramuscular triglyceride hydrolysis appears to be mediated entirely
      by beta 2-adrenergic stimulation. Endurance training substantially enhances fatty
      acid oxidative capacity in skeletal muscle and increases the proportion of energy
      derived from fatty acid oxidation during exercise. In addition, the
      sympathoadrenal response to exercise is markedly blunted in the trained state.
      Studies conducted in our laboratory indicate that plasma FFA and glycerol
      concentrations and whole body FFA uptake and oxidation are all decreased during
      moderate-intensity exercise at the same absolute work rate after physical
      conditioning, probably because of the reduction of sympathoadrenal activity.
      However, the lipolytic response to catecholamines also is enhanced in trained
      subjects. Perhaps as a consequence, the magnitude of the decrease in lipolysis
      and plasma FFA oxidation is less than the decrement in sympathoadrenal activity
      in the same individuals during exercise in the trained state. Other
      investigations were conducted in our laboratory to determine the source of the
      additional fatty acids oxidized in physically conditioned subjects. These studies
      demonstrated that during moderate-intensity exercise at the same absolute work
      rate, depletion of triglycerides from within skeletal muscle fibers was twice as
      great after, as opposed to, before training. Regardless of training status,
      intramuscular triglyceride use accounted for about 90% of the oxidized fatty
      acids that were not supplied from adipose tissue via the plasma. Intramuscular
      triglycerides were the source of virtually all of the additional fatty acids
      oxidized in the trained state. Both before and after physical conditioning they
      explained the discrepancy between the rates of plasma FFA and total fat oxidation
      during moderate-intensity exercise of up to 2 hr in duration.

PMID- 8744252
TI  - Growth, physical activity, and bone mineral acquisition.

PMID- 8744253
TI  - Exercise training and the cross-stressor adaptation hypothesis.

PMID- 8744254
TI  - Contractile activity-induced mitochondrial biogenesis in skeletal muscle.

PMID- 8744255
TI  - Thyroid hormone: modulation of muscle structure, function, and adaptive responses
      to mechanical loading.

PMID- 8744256
TI  - Strength and power training: physiological mechanisms of adaptation.
AB  - Adaptations in resistance training are focused on the development and maintenance
      of the neuromuscular unit needed for force production [97, 136]. The effects of
      training, when using this system, affect many other physiological systems of the
      body (e.g., the connective tissue, cardiovascular, and endocrine systems) [16,
      18, 37, 77, 83]. Training programs are highly specific to the types of adaptation
      that occur. Activation of specific patterns of motor units in training dictate
      what tissue and how other physiological systems will be affected by the exercise
      training. The time course of the development of the neuromuscular system appears
      to be dominated in the early phase by neural factors with associated changes in
      the types of contractile proteins. In the later adaptation phase, muscle protein
      increases, and the contractile unit begins to contribute the most to the changes
      in performance capabilities. A host of other factors can affect the adaptations,
      such as functional capabilities of the individual, age, nutritional status, and
      behavioral factors (e.g., sleep and health habits). Optimal adaptation appears to
      be related to the use of specific resistance training programs to meet individual
      training objectives.

PMID- 8744257
TI  - Response of the neuromuscular unit to spaceflight: what has been learned from the
      rat model.
AB  - Despite the inherent limitations placed on spaceflight investigations, much has
      been learned about the adaptations of the neuromuscular system to weightlessness
      from studies of rats flown for relatively short periods (approximately 4-22
      days). Below is a summary of the major effects of spaceflight observed in muscles
      of rats that are not in their rapid growth stage: 1. Skeletal muscles atrophy
      rapidly during spaceflight; significant atrophy is observed as early as after 4
      days of flight. 2. The atrophic response appears to be related to the primary
      function of the muscle. In the hindlimb, the relative amount of atrophy can be
      characterized as slow extensors > fast extensors > fast flexors. This pattern of
      relative atrophy does not appear to be occurring in the forelimb; however, not
      enough data are available to draw any definitive conclusions at this time. 3.
      Both slow and fast fibers atrophy during spaceflight, with the largest fibers
      within an individual muscle generally showing the greatest atrophic response.
      Interestingly, the amount of fiber atrophy appears to reach a plateau after about
      14 days of flight. 4. Adaptations have been observed in the concentration and
      content of all muscle proteins pools, with the protein pools in slow muscles the
      most affected. 5. Some slow and fast fibers in predominantly slow and fast
      muscles show shifts in their histochemical and biochemical properties, toward
      those observed in a "faster" phenotype. 6. Some fibers, presumably expressing
      slow MHC isoforms before flight, begin to express fast MHC isoforms during
      flight. 7. The oxidative capacity of the muscles or fibers is relatively
      unaffected by spaceflight, particularly in the slow muscles. Any change in whole
      body fatigability associated with spaceflight most likely reflects the loss in
      muscle and fiber mass. 8. The glycolytic capacity of the muscles and muscle
      fibers is enhanced after spaceflight. This metabolic adaptation seems to be
      related to the shift in the contractile proteins towards "faster" isoforms. 9.
      The vascularity of muscles appears to be maintained after flight, based, at
      least, on histological observations of capillarity. 10. The force capabilities of
      the muscles and fibers appear to decrease in parallel with the decreases in size,
      i.e., the specific tension is not significantly affected after flight. 11.
      Changes in the speed-related properties of the slow muscles are consistent with
      the adaptations in the myosin molecule, i.e., the slow muscles and some fibers in
      the slow muscles become "faster." 12. Some muscle fiber and neuromuscular
      junction damage has been observed after flight, particularly in the slow muscles.
      The extent of damage may be related to the amount of time that the muscles are
      allowed to reload before removal, i.e., in general, shorter intervals result in
      less fiber damage. 13. Adaptations in the motor (ventral horn) and sensory
      (spinal ganglia) neurons have been quite variable, but this may be related to the
      amount of time that the muscles are allowed to reload before removal.
      Morphological adaptations after relatively short periods of reloading may reflect
      a decrease in the activation of the neural elements during flight.

PMID- 8744258
TI  - Muscle mechanics: adaptations with exercise-training.
AB  - Based on the MHC isoform pattern, adult mammalian limb skeletal muscles contain
      two and, in some species, three types of fast fibers (Type IIa, IIx, and IIb),
      and one slow fiber (Type I). Slow muscles, such as the soleus, contain primarily
      the slow Type I fiber, whereas fast-twitch muscles are composed primarily of a
      mixture of the fast myosin isozymes. Force generation involves cross-bridge
      interaction and transition from a weakly bound, low-force state (AM-ADP-P(i)) to
      the strongly bound, high-force state (AM-ADP). This transition is thought to be
      rate limiting in terms of dP/dt, and the high-force state is the dominant cross
      bridge form during a peak isometric contraction. Intact fast and slow skeletal
      muscles generate approximately the same amount of peak force (Po) of between 200
      and 250 kN.m-2. However, the rate of transition from the low- to high-force state
      shows Ca2+ sensitivity and is 7-fold higher in fast-twitch, as compared to slow
      twitch, skeletal muscle fibers. Fiber Vo or the maximal cross-bridge cycle rate
      is highly correlated with and thought to be dependent on the specific activity of
      the myosin or myofibrillar ATPase. The hierarchy for Vo is the Type IIb > IIx >
      IIa > I. This functional difference for the fast fiber types explains the higher
      Vo observed in the predominantly Type IIb SVL vs. the mixed fast Type IIa and IIb
      EDL muscle. A plot of Vo vs. species size demonstrates that an inverse
      relationship exists between Vo and body mass. From the standpoint of work
      capacity, the important property is power output. An analysis of individual
      muscles indicates that peak power is obtained at loads considerably below 50% of
      Po. Individuals with a high percentage of fast-twitch fibers generate a greater
      torque and higher power at a given velocity than those with predominantly slow
      twitch fibers. In humans, mean peak power occurred in a ratio of 10:5:1 for the
      Type IIb, IIa, and I fibers. The in vivo measurement of the torque-velocity
      relationship and Vmax in human muscle is difficult because of limitations
      inherent in the equipment used and the inability to study the large limb muscles
      independently. Nevertheless, the in vivo torque-velocity relationships are
      similar to those measured in vitro in animals. This observation suggests that
      little central nervous system inhibition exists and that healthy subjects are
      able to achieve maximal activation of their muscles. Although peak isometric
      tension is not dependent on fiber type distribution, a positive correlation
      exists between the percentage of fast fibers and peak torque output at moderate
      to-high angular isokinetic velocities. Consequently, peak power output is
      substantially greater in subjects possessing a predominance of fast fibers. The
      mechanical properties of slow and fast muscles do adapt to programs of regular
      exercise. Endurance exercise training has been shown to increase the Vo of the
      slow soleus by 20%. This increase could have been caused by either a small
      increase in all, or most, of the fibers, or to a conversion of a few fibers from
      slow to fast. Recently, the increase was shown to be caused by the former, as the
      individual slow Type I fibers of the soleus showed a 20% increase in Vo, but
      there was little or no change in the percentage of fast fibers. The increased Vo
      was correlated with, and likely caused by, an increased fiber ATPase. We
      hypothesize that the increased ATPase and cross-bridge cycling speed might be
      attributable to an increased expression of fast MLCs in the slow Type I fibers
      (Fig. 14.10). This hypothesis is based on the fact that light chains have been
      shown to be involved in the power stroke, and removal of light chains depresses
      force and velocity. Regular endurance exercise training had no effect on fiber
      size, but with prolonged durations of daily training it depressed Po and peak
      power. When the training is maintained over prolonged periods, it may even induce
      atrophy of the slow Type I and fast Type IIa fibers. (ABSTRACT TRUNCATED)

PMID- 8744259
TI  - Magnetic resonance imaging and spectroscopy in studying exercise in children.

PMID- 8744260
TI  - History of phosphoinositide research.

PMID- 8744261
TI  - Phosphoinositides and synaptic transmission.

PMID- 8744262
TI  - Control of the Ca2+ release induced by myo-inositol trisphosphate and the
      implication in signal transduction.

PMID- 8744263
TI  - Regulation of the actin cytoskeleton by inositol phospholipid pathways.

PMID- 8744264
TI  - Protein phosphorylation and signal transduction.

PMID- 8744265
TI  - Structural and functional roles of glycosylphosphoinositides.

PMID- 8744266
TI  - Inositol pentakis- and hexakisphosphate metabolism adds versatility to the
      actions of inositol polyphosphates. Novel effects on ion channels and protein
      traffic.

PMID- 8744267
TI  - Inositol phosphates and their metabolism in plants.

PMID- 8744268
TI  - Genetics of myo-inositol phosphate synthesis and accumulation.

PMID- 8744269
TI  - Metabolism of myo-inositol phosphates and the alternative pathway in generation
      of myo-inositol trisphosphate involved in calcium mobilization in plants.

PMID- 8744270
TI  - Phosphoinositide turnover and its role in plant signal transduction.

PMID- 8744271
TI  - Light-induced signal transduction pathway involving inositol phosphates.

PMID- 8744273
TI  - An approach to the diagnosis of soft tissue tumors.

PMID- 8744272
TI  - Synthesis, separation, and identification of different inositol phosphates.

PMID- 8744274
TI  - Cytogenetics and molecular biology of soft tissue tumors.
AB  - Characteristic genetic aberrations have been identified in many soft tissue
      tumors, and it is likely that several of these aberrations, e.g., the
      translocation of chromosomes X and 18 in synovial sarcoma, will play an
      increasing diagnostic role. It is fascinating that most of the consistent soft
      tissue tumor translocations result in fusion genes, and these fusion genes encode
      proteins, which in turn regulate the expression of other genes. Thus, many soft
      tissue tumor translocations represent the first steps in complicated cascades of
      events contributing to deregulated tumor cell growth. Although a number of
      translocations appear to be useful in diagnosis, it should be emphasized that
      cytogenetic and molecular detection of chromosome translocations and gene fusions
      is not always straightforward. Cytogenetic and molecular analyses are perhaps
      best reserved for the subgroup of undifferentiated small round cell or spindle
      cell sarcomas, which remain unclassified after histological, immunohistochemical,
      and ultrastructural studies. Tumor specimens frozen at -70 degrees C can be used
      subsequently for FISH and PCR studies, although the opportunity to karyotype such
      specimens is lost upon freezing.

PMID- 8744275
TI  - Immunohistochemistry in the differential diagnosis of soft tissue tumors.
AB  - Immunohistochemical reagents have allowed us to analyze each and every soft
      tissue lesion over the past decade. What has been learned has been
      extraordinarily valuable and the fact that these reagents exist has undoubtedly
      led to more accurate diagnoses on the whole. We have learned to speak of
      "differentiation" rather than "histogenesis." We have also learned that, as each
      marker has been held up to the test of time, there are very few perfect markers.
      Interpretation must always be made with (1) full knowledge of the phenotypic
      range of each marker, (2) knowledge of the range of marker reactivity of each
      tumor or lesion, and (3) the all-important clinico-morphologic setting, which
      must continue to weigh heavily in the diagnostic process.

PMID- 8744276
TI  - Pathology of the major peripheral nerve sheath neoplasms.

PMID- 8744277
TI  - Fibrohistiocytic tumors.

PMID- 8744278
TI  - Vascular tumors: an update with emphasis on the diagnosis of angiosarcoma and
      borderline vascular neoplasms.
AB  - It is clear from this selective review that the category of vascular tumors
      remains a great source of interest and diagnostic challenge because of its
      complex and heterogeneous constituents. Accurate diagnosis of the relatively
      infrequent angiosarcomas, with particular emphasis on avoiding overdiagnosis,
      remains crucial since the clinical outcome is generally very poor, especially
      when compared with the relatively innocent angiomatous lesions often mistaken for
      it. Equally, it is important to avoid confusing either spindle cell
      hemangioendothelioma or tufted angioma with Kaposi's sarcoma inasmuch as the
      connotations of the latter (especially in young patients) are considerable.
      Finally, the concept of borderline malignancy in vascular tumors is evolving and
      is still poorly defined. However, the number of tumors often placed in this
      category is expanding, and the indolent or unpredictable biologic behavior of
      these tumors will continue to pose problems and questions for pathologist and
      clinician alike.

PMID- 8744279
TI  - Lipomatous tumors.
AB  - Lipomatous tumors are a common group of mesenchymal lesions. Over the years the
      major changes in the classification of lipomatous tumors have included the
      addition of several new variants of lipoma, the use of the term atypical lipoma
      for well differentiated liposarcoma of the subcutaneous tissue, and recognition
      of the entity dedifferentiated liposarcoma. Lipomas, the most common lipomatous
      tumor, account for nearly one-half of all benign lesions. In their typical form
      they seldom present diagnostic problems for the pathologist. However, lipomas
      occurring in deep locations (e.g., intramuscular lipoma, perineural lipoma) or
      those having unusual features (e.g., chondroid lipoma, lipoma with hibernoma,
      cellular angiolipoma, spindle cell/pleomorphic lipoma) may be confused with
      liposarcoma. Recent cytogenetic studies have reaffirmed the separate nature of
      many of the variants of lipoma. Solitary lipomas commonly have rearrangements of
      chromosome 12, a finding not encountered in multiple lipomas or in spindle cell/
      pleomorphic lipoma. Liposarcoma is the most common adult soft tissue sarcoma. It
      seldom arises from subcutaneous tissues or from preexisting lipomas, and is
      seldom found in children. The hallmark of liposarcoma is the immature fat cell or
      lipoblast. Diagnostic lipoblasts have an eccentric, hyperchromatic nucleus, which
      is indented or scalloped by the presence of one or more fat vacuoles. It is
      important that these cells occur in the appropriate histologic background because
      similar cells can be seen in a variety of nonlipomatous lesions (e.g., silicone
      reaction). Failure to apply strict criteria in identifying such cells and in
      noting the milieu in which they occur can lead to overdiagnosis of liposarcoma.
      Liposarcomas are divided into several subtypes: well differentiated, myxoid,
      round cell, pleomorphic, and dedifferentiated. Liposarcomas can be conceptualized
      as occurring in two broad groups, myxoid/round cell liposarcoma and well
      differentiated/dedifferentiated liposarcoma. Myxoid/round cell liposarcomas occur
      in middle-aged adults primarily as an extremity lesion. Tumors range from pure
      myxoid (low grade) to pure round cell (high-grade lesions) with some cases having
      transitional features. Behavior can be related to the amount of round cell areas.
      A consistent chromosome abnormality t(12;16) characterizes this spectrum of
      lesions. Well differentiated/dedifferentiated liposarcomas, in contrast, occur in
      late adult life as extremity or retroperitoneal lesions. They consist of mature
      fat interlaced with atypical hyperchromatic cells and rare lipoblasts. These
      lesions recur commonly, but they do not metastasize. Their behavior is strongly
      influenced by location, with retroperitoneal lesions having the worse prognosis.
      As a long-term complication of the disease, these lesions may progress
      histologically (dedifferentiate), a phenomenon that confers upon them metastatic
      potential. Dedifferentiation is largely a time-dependent phenomenon that occurs
      in sites in which there is a high likelihood for clinical persistence of disease
      (e.g., the retroperitoneum). Dedifferentiated liposarcomas occur in an age group
      similar to well differentiated liposarcoma, but are found far more commonly in
      the retroperitoneum. Most occur as de novo lesions, with only a small percentage
      occurring as a late complication of well differentiated liposarcoma, as described
      above. They consist of well differentiated areas associated with nonlipogenic
      sarcoma usually resembling high-grade malignant fibrous histiocytoma or
      fibrosarcoma. However, the range of histologic features occurring in the
      dedifferentiated areas is more varied than previously appreciated. Low-grade
      areas resembling fibromatosis or low-grade fibrosarcoma may be seen as the sole
      expression of dedifferentiation or may co-exist with high-grade sarcoma.
      (ABSTRACT TRUNCATED)

PMID- 8744280
TI  - Sarcomas: the role of adjuvant chemotherapy and a proposed new staging system.

PMID- 8744281
TI  - Enzyme immunoassay for conjugated cholic and 1 beta-hydroxycholic acids in urine
      of early infancy.
AB  - A direct competitive heterologous enzyme immunoassay (EIA) for conjugated cholic
      acid (CA) was developed using horseradish peroxidase labeled antigen having a
      shorter bridge length than that of the immunogen. An appropriate dose-response
      curve for conjugated CA was obtained in the range of 0.05-50 ng/well. Specificity
      of the EIA proved satisfactory in terms of cross-reactivities to 23 kinds of
      related bile acids. The proposed method was evaluated to be useful for the
      determination of conjugated CA in urine with acceptable accuracy and inter- and
      intra-assay precision. The results of analysis showed a reverse relationship
      between age and urinary excretion ratio of conjugated 1 beta-hydroxy-CA to
      conjugated CA in the first 9 months after birth.

PMID- 8744282
TI  - An enzyme-linked immunosorbent assay (ELISA) for the measurement of activated
      factor XII (Hageman factor) in human plasma.
AB  - A direct enzyme-linked immunosorbent assay (ELISA) employing 2/215 mouse
      monoclonal hybridoma antibody is described. The assay is capable of detecting
      activated factor XII in human plasma and can be used to assess early detection of
      the intrinsic blood coagulation pathway. No cross reactivity with human factor
      XII zymogen has been found. The assay was used to assess activation of factor XII
      in patients with renal failure, pregnancy and diabetes compared to a control
      group.

PMID- 8744283
TI  - Enzyme-linked immunosorbent assay of neocarzinostatin chromophore (NCS-chr) by
      use of a monoclonal antibody against NCS-chr analog.
AB  - A monoclonal antibody against NCS-chr was prepared and characterized. Because of
      the instability of NCS-chr, chemically synthesized stable analog compound, termed
      PS, was used as a hapten of immunogen. The obtained antibody, termed APS, reacted
      with NCS-chr, but neither with NCS, NCS-polystyrene-maleic acid conjugate
      (SMANCS), nor UV-irradiated NCS-chr. Epitope analysis using the compounds that
      have a structure similar to PS showed that APS recognized the total structure,
      particularly cyclopenten moiety, of PS. These results suggest that APS recognizes
      the enediyne structure of NCS-chr. Next, the inhibition enzyme-linked
      immunosorbent assay (ELISA) for determination of NCS-chr was established. The
      standard curve showed that the microgram order of NCS-chr were accurately
      measurable by the established ELISA. Furthermore, it was revealed that the
      established ELISA was more sensitive than the antibiotic activity determination,
      termed Bio-assay. The established ELISA will be useful as a quantitative method
      of NCS-chr.

PMID- 8744284
TI  - The quantitation of coupled bead antibody by enzyme-linked immunosorbent assay.
AB  - Quantitation of antibody coupled to a derivatized polystyrene bead through a
      bifunctional cross linker can be accomplished by a competitive enzyme-linked
      immunosorbent assay (ELISA) method. This sensitive method is less subject to
      interference than other protein assay methods such as bicinchoninic acid (BCA) or
      Lowry. The competitive ELISA method consists of incubating the coupled bead with
      a (20/80) weight ratio of goat anti mouse kappa alkaline phosphatase/goat anti
      mouse kappa (GAMKAP/GAMK) for 1.5 hours at 37 degrees C, washing, adding p
      nitrophenyl phosphate (PNPP) substrate, and reading the absorbance at 405/450 nm.
      A standard curve is established with radiolabeled antibody beads for microgram
      quantitation.

PMID- 8744285
TI  - Sensitive detection of Plasmodium vivax in blood by a cell-ELISA using a
      monoclonal antibody.
AB  - An IgM monoclonal antibody (7C5B71) which reacted with the blood stages of
      Plasmodium vivax, but not with those of Plasmodium falciparum was used in a cell
      ELISA to detect parasites in samples of peripheral blood. Blood thin smears were
      probed with monoclonal antibody 7C5B71 and then reacted with a peroxidase
      conjugate of the appropriate specificity and the insoluble chromogen amino-ethyl
      carbazole. Infected cells which appeared dark red coloured were rapidly
      identified under a light microscope using a low magnification. The conventional
      microscopic examination of thin films coloured with Giemsa was used as reference
      test. Under laboratory conditions the test showed a positive result in samples
      with a level of parasitaemia of < or = 500 parasites/microliter of blood. In a
      preliminary field trial the test showed 100 % specificity for the diagnosis of P.
      vivax malaria.

PMID- 8744286
TI  - Quantitation of 3'-amino-3'-deoxythymidine (AMT), a toxic catabolite of 3'-azido
      3'-deoxythymidine (AZT), by competitive ELISA.
AB  - In the present study, a competitive ELISA technique was developed to specifically
      quantitate 3'-amino-3'-deoxythymidine (AMT), a toxic catabolite of 3'-azido-3'
      deoxythymidine (AZT) detected in serum from AZT-treated patients. In order to
      eliminate cross-reacting AZT, serum sample was extracted with ethylacetate and
      then AMT was acetylated (Ac-AMT). A 5'-hemisuccinate-AMT-horseradish peroxidase
      conjugate was used as a tracer in the presence of anti-AMT rabbit antibodies
      which were raised against a 5' hemisuccinate-AMT-bovine serum albumin immunogen.
      Bound/free separation was achieved with an anti-rabbit IgG mouse monoclonal
      antibody insolubilized onto a microtiter plate. The limit of quantification of Ac
      AMT was as low as 0.4 ng/ml in serum samples. This ELISA technique was applied
      for monitoring AMT plasma levels in patients receiving AZT therapy. The intra and
      inter-individual variations of the AZT/AMT plasma concentration ratios underlined
      the need for such a specific test in studying the formation of this toxic
      catabolite.

PMID- 8744287
TI  - Frequency tuning in the turtle's cochlea: who sets the stage?

PMID- 8744288
TI  - Calculated coupling of electron and proton transfer in the photosynthetic
      reaction center of Rhodopseudomonas viridis.
AB  - Based on new Rhodopseudomonas (Rp.) viridis reaction center (RC) coordinates with
      a reliable structure of the secondary acceptor quinone (QB) site, a continuum
      dielectric model and finite difference technique have been used to identify
      clusters of electrostatically interacting ionizable residues. Twenty-three
      residues within a distance of 25 A from QB (QB cluster) have been shown to be
      strongly electrostatically coupled to QB, either directly or indirectly. An
      analogous cluster of 24 residues is found to interact with QA (QA cluster). Both
      clusters extend to the cytoplasmic surface in at least two directions. However,
      the QB cluster differs from the QA cluster in that it has a surplus of acidic
      residues, more strong electrostatic interactions, is less solvated, and
      experiences a strong positive electrostatic field arising from the polypeptide
      backbone. Consequently, upon reduction of QA or QB, it is the QB cluster, and not
      the QA cluster, which is responsible for substoichiometric proton uptake at
      neutral pH. The bulk of the changes in the QB cluster are calculated to be due to
      the protonation of a tightly coupled cluster of the three Glu residues (L212,
      H177, and M234) within the QB cluster. If the lifetime of the doubly reduced
      state QB2- is long enough, Asp M43 and Ser L223 are predicted to also become
      protonated. The calculated complex titration behavior of the strongly interacting
      residues of the QB cluster and the resulting electrostatic response to electron
      transfer may be a common feature in proton-transferring membrane protein
      complexes.

PMID- 8744289
TI  - A mechanism for synaptic frequency detection through autophosphorylation of CaM
      kinase II.
AB  - A model for the regulation of CaM kinase II is presented based on the following
      reported properties of the molecule: 1) The holoenzyme is composed of 8-12
      subunits, each with the same set of autophosphorylation sites; 2)
      Autophosphorylation at one group of sites (A sites) requires the presence of Ca2+
      and causes a subunit to remain active following the removal of Ca2+; 3)
      Autophosphorylation at another group of sites (B sites) occurs only after the
      removal of Ca2+ but requires prior phosphorylation of a threshold number of A
      sites within the holoenzyme. Because B-site phosphorylation inhibits
      Ca2+/calmodulin binding, we propose that, for a given subunit, phosphorylation of
      a B site before an A site prevents subsequent phosphorylation at the A site and
      thereby locks that subunit in an inactive state. The model predicts that a
      threshold activation by Ca2+ will initiate an "autophosphorylation phase." Once
      started, intra-holoenzyme autophosphorylation will proceed, on A sites during
      periods of high [Ca2+] and on B sites during periods of low [Ca2+]. At
      "saturation," that is when every subunit has been phosphorylated on a B site, the
      number of phosphorylated A sites and, therefore, the kinase activity will reflect
      the relative durations of periods of high [Ca2+] to periods of low [Ca2+] that
      occurred during the autophosphorylation phase. Using a computer program designed
      to simulate the above mechanism, we show that the ultimate state of
      phosphorylation of an array of CaM kinase II molecules could be sensitive to the
      temporal pattern of Ca2+ pulses. We speculate that such a mechanism may allow
      arrays of CaM kinase II molecules in postsynaptic densities to act as synaptic
      frequency detectors involved in setting the direction and level of synaptic
      modification.

PMID- 8744291
TI  - Model of P- and T-electroreceptors of weakly electric fish.
AB  - To clarify the microscopic mechanisms by which P- and T-receptors encode
      amplitude modulation and zero crossing time of jamming signals, we present a
      model of P- and T-receptors based on their physiological and anatomical
      properties. The model consists of a receptor cell, supporting cells, and an
      afferent nerve fiber. The basal membrane of the receptor cell includes voltage
      sensitive Ca2+ channels, Ca(2+)-activated K+ channels, and leak channels of Na+,
      K+, and Cl-. The driving force of potential change under stimulation is generated
      by the voltage-sensitive Ca2+ channels, and the suppressing force of the change
      is generated by Ca(2+)-activated K+ channels. It has been shown that in T
      receptor cells the driving force is much stronger than the suppressing force,
      whereas in P-receptor cells the driving force is comparable with the suppressing
      force. The difference in various kinds of response properties between P- and T
      receptors have been consistently explained based on the difference in the
      relative strengths of the driving and suppressing forces between P- and T
      receptor cells. The response properties considered are encoding function,
      probability of firing of afferent nerve, pattern of damped oscillation, shape of
      tuning curves, values of the optimum frequency, and response latency.

PMID- 8744290
TI  - Reversible surface aggregation in pore formation by pardaxin.
AB  - The mechanism of leakage induced by surface active peptides is not yet fully
      understood. To gain insight into the molecular events underlying this process,
      the leakage induced by the peptide pardaxin from phosphatidylcholine/
      phosphatidylserine/cholesterol large unilamellar vesicles was studied by
      monitoring the rate and extent of dye release and by theoretical modeling. The
      leakage occurred by an all-or-none mechanism: vesicles either leaked or retained
      all of their contents. We further developed a mathematical model that includes
      the assumption that certain peptides become incorporated into the vesicle bilayer
      and aggregate to form a pore. The current experimental results can be explained
      by the model only if the surface aggregation of the peptide is reversible.
      Considering this reversibility, the model can explain the final extents of
      calcein leakage for lipid/peptide ratios of > 2000:1 to 25:1 by assuming that
      only a fraction of the bound peptide forms pores consisting of M = 6 +/- 3
      peptides. Interestingly, less leakage occurred at 43 degrees C, than at 30
      degrees C, although peptide partitioning into the bilayer was enhanced upon
      elevation of the temperature. We deduced that the increased leakage at 30 degrees
      C was due to an increase in the extent of reversible surface aggregation at the
      lower temperature. Experiments employing fluorescein-labeled pardaxin
      demonstrated reversible aggregation of the peptide in suspension and within the
      membrane, and exchange of the peptide between liposomes. In summary, our
      experimental and theoretical results support reversible surface aggregation as
      the mechanism of pore formation by pardaxin.

PMID- 8744292
TI  - Validity of the rapid buffering approximation near a point source of calcium
      ions.
AB  - In the presence of rapid buffers the full reaction-diffusion equations describing
      Ca2+ transport can be reduced using the rapid buffering approximation to a single
      transport equation for [Ca2+]. Here we simulate the full and reduced equations,
      exploring the conditions necessary for the validity of the rapid buffering
      approximation for an isolated Ca2+ channel or a cluster of channels. Using a
      point source and performing numerical simulations of different durations, we
      quantify the error of the rapid buffering approximation as a function of buffer
      and source parameters as well as the time and spatial scale set by the resolution
      of confocal microscopic measurements. We carry out simulations of Ca2+ "sparks"
      and "puffs," both with and without the indicator dye Ca2+ Green-1, and find that
      the rapid buffering approximation is excellent. These calculations also show that
      the traditional calculation of [Ca2+] from a fluorescence signal may grossly
      underestimate the true value of [Ca2+] near a source. Finally, we use the full
      model to simulate the transient Ca2+ domain near the pore of an open Ca2+ channel
      in a cell dialyzed with millimolar concentrations of 1,2-bis(2
      aminophenoxy)ethane-N,N,N,N-tetraacetic acid or EGTA. In this regime, where the
      rapid buffering approximation is poor. Neher's equation for the steady-state Ca2+
      profile is shown to be a reliable approximation adjacent to the pore.

PMID- 8744293
TI  - Self-organized segmentation of time series: separating growth hormone secretion
      in acromegaly from normal controls.
AB  - The pulsatile pattern of growth hormone (GH) secretion was assessed by sampling
      blood every 10 min over 24 h in healthy subjects (n = 10) under normal food
      intake and under fasting conditions (n = 6) and in patients with a GH-producing
      tumor (acromegaly, n = 6), before and after treatment with the somatostatin
      analog octreotide. Using autocorrelation, we found no consistent separation in
      the temporal dynamics of GH secretion in healthy controls and acromegalic
      patients. Time series prediction based on a single neural network has recently
      been demonstrated to separate the secretory dynamics of parathyroid hormone in
      healthy controls from osteoporotic patients. To better distinguish the
      differences in GH dynamics in healthy subjects and patients, we tested time
      series predictions based on a single neural network and a more refined system of
      multiple neural networks acting in parallel (adaptive mixtures of local experts).
      Both approaches significantly separated GH dynamics under the various conditions.
      By performing a self-organized segmentation of the alternating phases of
      secretory bursts and quiescence of GH, we significantly improved the performance
      of the multiple network system over that of the single network. It thus may
      represent a potential tool for characterizing alterations of the dynamic
      regulation associated with diseased states.

PMID- 8744294
TI  - Effect of supercoiling on the juxtaposition and relative orientation of DNA
      sites.
AB  - There are many proteins that interact simultaneously with two or more DNA sites
      that are separated along the DNA contour. These sites must be brought close
      together to form productive complexes with the proteins. We used Monte Carlo
      simulation of supercoiled DNA conformations to study the effect of supercoiling
      and DNA length on the juxtaposition of DNA sites, the angle between them, and the
      branching of the interwound superhelix. Branching decreases the probability of
      juxtaposition of two DNA sites but increases the probability of juxtaposition of
      three sites at branch points. We found that the number of superhelix branches
      increases linearly with the length of DNA from 3 to 20 kb. The simulations showed
      that for all contour distances between two sites, the juxtaposition probability
      in supercoiled DNA is two orders of magnitude higher than in relaxed DNA.
      Supercoiling also results in a strong asymmetry of the angular distribution of
      juxtaposed sites. The effect of supercoiling on site-specific recombination and
      the introduction of supercoils by DNA gyrase is discussed in the context of the
      simulation results.

PMID- 8744295
TI  - A developmental model for generating frequency maps in the reptilian and avian
      cochleas.
AB  - Hair cells in the turtle cochlea are frequency-tuned by a mechanism involving the
      combined activation of voltage-sensitive Ca2+ channels and Ca(2+)-activated K+
      (KCa) channels. The main determinants of a hair cell's characteristic frequency
      (Fo) are the KCa channels' density and kinetics, both of which change
      systematically with location in the cochlea in conjunction with the observed
      frequency map. We have developed a model based on the differential expression of
      two KCa channel subunits, which when accompanied by concurrent changes in other
      properties (e.g., density of Ca2+ channels and inwardly rectifying K+ channels),
      will generate sharp tuning at frequencies from 40 to 600 Hz. The kinetic
      properties of the two subunits were derived from previous single-channel
      analysis, and it was assumed that the subunits (A and B) combine to form five
      species of tetrameric channel (A4, A3B, A2B2, AB3, and B4) with intermediate
      kinetics and overlapping distribution. Expression of KCa and other channels was
      assumed to be regulated by diffusional gradients in either one or two chemicals.
      The results are consistent with both current- and voltage-clamp data on turtle
      hair cells, and they show that five channel species are sufficient to produce
      smooth changes in both Fo and kinetics of the macroscopic KCa current. Other
      schemes for varying KCa channel kinetics are examined, including one that allows
      extension of the model to the chick cochlea to produce hair cells with Fo's from
      130 to 4000 Hz. A necessary assumption in all models is a gradient in the values
      of the parameters identified with the cell's cytoplasmic Ca2+ buffer.

PMID- 8744296
TI  - Cytosolic and mitochondrial [Ca2+] in whole hearts using indo-1 acetoxymethyl
      ester: effects of high extracellular Ca2+.
AB  - Assessment of free cytosolic [Ca2+] ([Ca2+]c) using the acetoxymethyl ester (AM)
      form of indo-1 may be compromised by loading of indo-1 into noncytosolic
      compartments, primarily mitochondria. To determine the fraction of noncytosolic
      fluorescence in whole hearts loaded with indo-1 AM, Mn2+ was used to quench
      cytosolic fluorescence. Residual (i.e., noncytosolic) fluorescence was subtracted
      from the total fluorescence before calculating [Ca2+]c. Noncytosolic fluorescence
      was used to estimate mitochondrial [Ca2+]. In hearts paced at 5 Hz (N = 17),
      noncytosolic fluorescence was 0.61 +/- 0.06 and 0.56 +/- 0.07 of total
      fluorescence at lambda 385 and lambda 456, respectively. After taking into
      account noncytosolic fluorescence, systolic and diastolic [Ca2+]c was 673 +/- 72
      and 132 +/- 9 nM, respectively, noncytosolic [Ca2+] was 183 +/- 36 nM and
      increased to 272 +/- 12 when extracellular Ca2+ was increased from 2 to 6 mM.
      This increase in noncytosolic [Ca2+] was inhibited by ruthenium red, a blocker of
      Ca2+ uptake by mitochondria. We conclude that cytosolic and mitochondrial [Ca2+]
      can be determined in whole hearts loaded with indo-1 AM by using Mn2+ to quench
      cytosolic fluorescence.

PMID- 8744297
TI  - Modal behavior of the mu 1 Na+ channel and effects of coexpression of the beta 1
      subunit.
AB  - The adult rat skeletal muscle Na+ channel alpha-subunit (mu 1) appears to gate
      modally with two kinetic schemes when the channel is expressed in Xenopus
      oocytes. In the fast mode mu 1 single channels open only once or twice per
      depolarizing pulse, but in the slow mode the channels demonstrate bursting
      behavior. Slow-mode gating was favored by hyperpolarized holding potentials and
      slow depolarizing rates, whereas fast-mode gating was favored by depolarized
      holding potentials and rapid depolarizations. Single-channel studies showed that
      coexpression of beta 1 reduces slow-mode gating, so that channels gate almost
      exclusively in the fast mode. Analysis of open-time histograms showed that mu 1
      and mu 1 + beta 1 both have two open-time populations with the same mean open
      times (MOTs). The difference lies in the relative sizes of the long and short MOT
      components. When beta 1 was coexpressed with mu 1 in oocytes, the long MOT
      fraction was greatly reduced. It appears that although mu 1 and mu 1 + beta 1
      share the same two open states, the beta 1-subunit favors the mode with the
      shorter open state. Examination of first latencies showed that it is likely that
      the rate of activation is increased upon coexpression with beta 1. Experiments
      also showed that the rate of activation for the fast mode of mu 1 is identical to
      that for mu 1 + beta 1 and is thus more rapid than the rate of activation for the
      slow mode. It can be concluded that beta 1 restores native-like kinetics in mu 1
      by favoring the fast-gating mode.

PMID- 8744298
TI  - Ion channels from synaptic vesicle membrane fragments reconstituted into lipid
      bilayers.
AB  - Cholinergic synaptic vesicles were isolated from the electric organ of Torpedo
      californica. Vesicle membrane proteins were reconstituted into planar lipid
      bilayers by the nystatin/ergosterol fusion technique. After fusion, a variety of
      ion channels were observed. Here we identify four channels and describe two of
      them in detail. The two channels share a conductance of 13 pS. The first is anion
      selective and strongly voltage dependent, with a 50% open probability at membrane
      potentials of -15 mV. The second channel is slightly cation selective and voltage
      independent. It has a high open probability and a subconductance state. A third
      channel has a conductance of 4-7 pS, similar to the subconductance state of the
      second channel. This channel is fairly nonselective and has gating kinetics
      different from those of the cation channel. Finally, an approximately 10-pS,
      slightly cation selective channel was also observed. The data indicate that there
      are one or two copies of each of the above channels in every synaptic vesicle,
      for a total of six channels per vesicle. These observations confirm the existence
      of ion channels in synaptic vesicle membranes. It is hypothesized that these
      channels are involved in vesicle recycling and filling.

PMID- 8744299
TI  - Sarcoplasmic reticulum lumenal Ca2+ has access to cytosolic activation and
      inactivation sites of skeletal muscle Ca2+ release channel.
AB  - The effects of sarcoplasmic reticulum lumenal (trans) Ca2+ on cytosolic (cis) ATP
      activated rabbit skeletal muscle Ca2+ release channels (ryanodine receptors) were
      examined using the planar lipid bilayer method. Single channels were recorded in
      symmetric 0.25 M KCl media with K+ as the major current carrier. With nanomolar
      [Ca2+] in both bilayer chambers, the addition of 2 mM cytosolic ATP greatly
      increased the number of short channel openings. As lumenal [Ca2+] was increased
      from < 0.1 microM to approximately 250 microM, increasing channel activities and
      events with long open time constants were seen at negative holding potentials.
      Channel activity remained low at positive holding potentials. Further increase in
      lumenal [Ca2+] to 1, 5, and 10 mM resulted in a decrease in channel activities at
      negative holding potentials and increased activities at positive holding
      potentials. A voltage-dependent activation by 50 microM lumenal Ca2+ was also
      observed when the channel was minimally activated by < 1 microM cytosolic Ca2+ in
      the absence of ATP. With microM cytosolic Ca2+ in the presence or absence of 2 mM
      ATP, single-channel activities showed no or only a weak voltage dependence. Other
      divalent cations (Mg2+, Ba2+) could not replace lumenal Ca2+. On the contrary,
      cytosolic ATP-activated channel activities were decreased as lumenal Ca2+ fluxes
      were reduced by the addition of 1-5 mM BaCl2 or MgCl2 to the lumenal side, which
      contained 50 microM Ca2+. An increase in [KCl] from 0.25 M to 1 M also reduced
      single-channel activities. Addition of the "fast" Ca2+ buffer 1,2-bis(2
      aminophenoxy)ethanetetraacetic acid (BAPTA) to the cls chamber increased
      cytosolic ATP-, lumenal Ca(2+)-activated channel activities to a nearly maximum
      level. These results suggested that lumenal Ca2+ flowing through the skeletal
      muscle Ca2+ release channel may regulate channel activity by having access to
      cytosolic Ca2+ activation and Ca2+ inactivation sites that are located in "BAPTA
      inaccessible" and "BAPTA-accessible" spaces, respectively.

PMID- 8744300
TI  - Effect of changing temperature on the ionic permeation through the cyclic GMP
      gated channel from vertebrate photoreceptors.
AB  - Native cGMP-gated channels were studied in rod outer segments of the larval tiger
      salamander Ambystoma tigrinum. The alpha subunit of the cGMP-gated channel from
      bovine rods, here referred to as the wild type (w.t.), and mutant channels were
      heterologously expressed in Xenopus laevis oocytes. These channels were studied
      in excised membrane patches in the inside-out configuration and were activated by
      the addition of 100 or 500 microM cGMP. The effect of temperature on the ionic
      permeation was studied. The macroscopic current flowing through the native
      channel at +100 mV had an activation energy of 35.8, 30, 31.8, 34.5, 41.3, and
      22.4 kJ mol-1 in the presence of Li+, Na+, K+, Rb+, Cs+, and NH4+, respectively.
      The macroscopic current flowing through the w.t. channel at +100 mV had an
      activation energy of 45.2, 38.2, 37.5, 47.3, 49.4, and 38.9 kJ mol-1 in the
      presence of Li+, Na+, K+, Rb+, Cs+, and NH4+, respectively. The activation energy
      of the macroscopic current flowing through the native and w.t. channels did not
      vary significantly when the ionic concentration of the permeant ion was changed
      between 2.5 and 110 mM. The activation energy of the single-channel current of
      the w.t. channel at +100 mV was 40.4 and 33 kJ mol-1 for Na+ and NH4+,
      respectively. The reversal potential of biionic solutions changed significantly
      with temperature. These results can be used to obtain an estimate of the
      enthalpic and entropic contributions to the barrier of the Gibbs free energy
      experienced by an ion during its permeation through the open channel. These
      estimates indicate that the ionic permeation and selectivity of the cGMP-gated
      channel are controlled both by enthalpic and entropic factors and that the
      selectivity of the native channel for Li+ over Na+ is primarily caused by
      entropic effects.

PMID- 8744301
TI  - Wanderlust kinetics and variable Ca(2+)-sensitivity of Drosophila, a large
      conductance Ca(2+)-activated K+ channel, expressed in oocytes.
AB  - Cloned large conductance Ca(2+)-activated K+ channels (BK or maxi-K+ channels)
      from Drosophila (dSlo) were expressed in Xenopus oocytes and studied in excised
      membrane patches with the patch-clamp technique. Both a natural variant and a
      mutant that eliminated a putative cyclic AMP-dependent protein kinase
      phosphorylation site exhibited large, slow fluctuations in open probability with
      time. These fluctuations, termed "wanderlust kinetics," occurred with a time
      course of tens of seconds to minutes and had kinetic properties inconsistent with
      simple gating models. Wanderlust kinetics was still observed in the presence of 5
      mM caffeine or 50 nM thapsigargin, or when the Ca2+ buffering capacity of the
      solution was increased by the addition of 5 mM HEDTA, suggesting that the
      wanderlust kinetics did not arise from Ca2+ release from caffeine and
      thapsigargin sensitive internal stores in the excised patch. The slow changes in
      kinetics associated with wanderlust kinetics could be generated with a discrete
      state Markov model with transitions among three or more kinetic modes with
      different levels of open probability. To average out the wanderlust kinetics,
      large amounts of data were analyzed and demonstrated up to a threefold difference
      in the [Ca2+]i required for an open probability of 0.5 among channels expressed
      from the same injected mRNA. These findings indicate that cloned dSlo channels in
      excised patches from Xenopus oocytes can exhibit large variability in gating
      properties, both within a single channel and among channels.

PMID- 8744302
TI  - Inorganic, monovalent cations compete with agonists for the transmitter binding
      site of nicotinic acetylcholine receptors.
AB  - The properties of adult mouse recombinant nicotinic acetylcholine receptors
      activated by acetylcholine (ACh+) or tetramethylammonium (TMA+) were examined at
      the single-channel level. The midpoint of the dose-response curve depended on the
      type of monovalent cation present in the extracellular solution. The shifts in
      the midpoint were apparent with both inward and outward currents, suggesting that
      the salient interaction is with the extracellular domain of the receptor. Kinetic
      modeling was used to estimate the rate constants for agonist binding and channel
      gating in both wild-type and mutant receptors exposed to Na+, K+, or Cs+. The
      results indicate that in adult receptors, the two binding sites have the same
      equilibrium dissociation constant for agonists. The agonist association rate
      constant was influenced by the ionic composition of the extracellular solution
      whereas the rate constants for agonist dissociation, channel opening, and channel
      closing were not. In low-ionic-strength solutions the apparent association rate
      constant increased in a manner that suggests that inorganic cations are
      competitive inhibitors of ACh+ binding. There was no evidence of an electrostatic
      potential at the transmitter binding site. The equilibrium dissociation constants
      for inorganic ions (Na+, 151 mM; K+, 92 mM; Cs+, 38 mM) and agonists (TMA+, 0.5
      mM) indicate that the transmitter binding site is hydrophobic. Under
      physiological conditions, about half of the binding sites in resting receptors
      are occupied by Na+.

PMID- 8744303
TI  - Neutron scattering in the plane of membranes: structure of alamethicin pores.
AB  - A technique of neutron in-plane scattering for studying the structures of peptide
      pores in membranes is described. Alamethicin in the inserted state was prepared
      and undeuterated and deuterated dilauroyl phosphatidylcholine (DLPC) hydrated
      with D2O or H2O. Neutron in-plane scattering showed a strong dependence on
      deuteration, clearly indicating that water is a part of the high-order structure
      of inserted alamethicin. The data are consistent with the simple barrel-stave
      model originally proposed by Baumann and Mueller. The theoretical curves computed
      with this model at four different deuteration conditions agree with the data in
      all cases. Both the diameter of the water pore and the effective outside diameter
      of the channel are determined accurately. Alamethicin forms pores in a narrow
      range of size. In a given sample condition, > 70% of the peptide forms pores of n
      and n +/- 1 monomers. The pore size varies with hydration and with lipid. In
      DLPC, the pores are made of n = 8-9 monomers, with a water pore approximately 18
      A in diameter and with an effective outside diameter of approximately 40 A. In
      diphytanoyl phosphatidylcholine, the pores are made of n approximately 11
      monomers, with a water pore approximately 26 A in diameter, with an effective
      outside diameter of approximately 50 A.

PMID- 8744304
TI  - Subunit interactions in the activation of cyclic nucleotide-gated ion channels.
AB  - Cyclic nucleotide-gated (CNG) ion channels of retinal photoreceptors and
      olfactory neurons are multimeric proteins of unknown stoichiometry. To
      investigate the subunit interactions that occur during CNG channel activation, we
      have used tandem cDNA constructs of the rod CNG channel to generate
      heteromultimeric channels composed of wild-type and mutant subunits. We
      introduced point mutations that affect channel activation: 1) D604M, which alters
      the relative ability of agonists to promote the allosteric conformational
      change(s) associated with channel opening, and 2) T560A, which primarily affects
      the initial binding affinity for cGMP, and to a lesser extent, the allosteric
      transition. At saturating concentrations of agonist, heteromultimeric channels
      were intermediate between wild-type and mutant homomultimers in agonist efficacy
      and apparent affinity for cGMP, cIMP, and cAMP, consistent with a model for the
      allosteric transition involving a concerted conformational change in all of the
      channel subunits. Results were also consistent with a model involving independent
      transitions in two or three, but not one or four, of the channel subunits. The
      behavior of the heterodimers implies that the channel stoichiometry is some
      multiple of 2 and is consistent with a tetrameric quaternary structure for the
      functional channel complex. Steady-state dose-response relations for
      homomultimeric and heteromultimeric channels were well fit by a Monod, Wyman, and
      Changeux model with a concerted allosteric opening transition stabilized by
      binding of agonist.

PMID- 8744305
TI  - Inward rectification of the IRK1 K+ channel reconstituted in lipid bilayers.
AB  - Inwardly rectifying potassium (K+) channels (IRK1) were incorporated into lipid
      bilayers to test the relative contributions of various mechanisms to inward
      rectification. IRK1 channels were expressed in Xenopus laevis oocytes and oocyte
      membrane vesicles containing the channels were fused with lipid bilayers. The
      major properties of the IRK1 channel were similar whether measured in the oocyte
      membrane or lipid bilayer; the single channel conductance was 21 pS in 140 mM
      symmetrical [K+] and varied as a square root of external [K+]. Importantly, IRK1
      channels display voltage-dependent inward rectification in the absence of
      divalent ions or charged regulators such as spermine, indicating that they
      possess an intrinsic rectification mechanism. Although rectification was
      significantly increased by either Mg2+ or spermine added to the cytoplasmic face
      of the channel, their effects could not be explained by simple block of the open
      pore. The Hille and Schwartz (1978) model, originally proposed to explain inward
      rectification by singly charged blocking particles, cannot be used to explain
      rectification by multiply charged blocking particles. As an alternative, we
      propose that in addition to a slow gating mechanism producing long lasting open
      and closed states, there is a distinct, intrinsic fast gating process amplified
      by cytoplasmic Mg2+ and/or polyamine binding to the channel.

PMID- 8744306
TI  - Identification of cystic fibrosis transmembrane conductance regulator channel
      lining residues in and flanking the M6 membrane-spanning segment.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) forms a chloride
      channel that is regulated by phosphorylation and ATP binding. Work by others
      suggested that some residues in the sixth transmembrane segment (M6) might be
      exposed in the channel and play a role in ion conduction and selectivity. To
      identify the residues in M6 that are exposed in the channel and the secondary
      structure of M6, we used the substituted cysteine accessibility method. We
      mutated to cysteine, one at a time, 24 consecutive residues in and flanking the
      M6 segment and expressed these mutants in Xenopus oocytes. We determined the
      accessibility of the engineered cysteines to charged, lipophobic, sulfhydryl
      specific methanethiosulfonate (MTS) reagents applied extracellularly. The
      cysteines substituted for Ile331, Leu333, Arg334, Lys335, Phe337, Ser341, Ile344,
      Arg347, Thr351, Arg352, and Gln353 reacted with the MTS reagents, and we infer
      that they are exposed on the water-accessible surface of the protein. From the
      pattern of the exposed residues we infer that the secondary structure of the M6
      segment includes both alpha-helical and extended regions. The diameter of the
      channel from the extracellular end to the level of Gln353 must be at least 6 A to
      allow the MTS reagents to reach these residues.

PMID- 8744307
TI  - Tolbutamide causes open channel blockade of cystic fibrosis transmembrane
      conductance regulator Cl- channels.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial Cl-
      channel that is regulated by protein kinase A and cytosolic nucleotides.
      Previously, Sheppard and Welsh reported that the sulfonylureas glibenclamide and
      tolbutamide reduced CFTR whole cell currents. The aim of this study was to
      quantify the effects of tolbutamide on CFTR gating in excised membrane patches
      containing multiple channels. We chose tolbutamide because weak (i.e., fast-type)
      open channel blockers introduce brief events into multichannel recordings that
      can be readily quantified by current fluctuation analysis. Inspection of current
      records revealed that the addition of tolbutamide reduced the apparent single
      channel current amplitude and increased the open-channel noise, as expected for a
      fast-type open channel blocker. The apparent decrease in unitary current
      amplitude provides a measure of open probability within a burst (P0 Burst), and
      the resulting concentration-response relationship was described by a simple
      Michaelis-Menten inhibition function. The concentration of tolbutamide causing a
      50% reduction of Po Burst (540 +/- 20 microM) was similar to the concentration
      producing a 50% inhibition of short-circuit current across T84 colonic epithelial
      cell monolayers (400 +/- 20 microM). Changes in CFTR gating were then quantified
      by analyzing current fluctuations. Tolbutamide caused a high-frequency Lorentzian
      (corner frequency, fc > 300 Hz) to appear in the power density spectrum. The fc
      of this Lorentzian component increased as a linear function of tolbutamide
      concentration, as expected for a pseudo-first-order open-blocked mechanism and
      yielded estimates of the on rate (koff = 2.8 +/- 0.3 microM-1 s-1), the off rate
      (kon = 1210 +/- 225 s-1), and the dissociation constant (KD = 430 +/- 80 microM).
      Based on these observations, we propose that there is a bimolecular interaction
      between tolbutamide and CFTR, causing open channel blockade.

PMID- 8744309
TI  - Electrochemical modeling of electron and proton transfer to ubiquinone-10 in a
      self-assembled phospholipid monolayer.
AB  - Ubiquinone-10 (UQ) was incorporated at concentrations ranging from 0.5 to 2 mol%
      in a self-assembled monolayer of dioleoylphosphatidylcholine (DOPC) deposited on
      a mercury drop electrode, and its electroreduction to ubiquinol (UQH2) was
      investigated in phosphate and borate buffers over the pH range from 7 to 9.5 by a
      computerized chronocoulometric technique. The dependence of the applied potential
      for a constant value of the faradaic charge due to UQ reduction upon the
      electrolysis time t at constant pH and upon pH at constant t was examined on the
      basis of a general kinetion approach. This permitted us to conclude that the
      reduction of UQ to UQH2 in DOPC monolayers takes place via the reversible uptake
      of one electron with the formation of the semiubiquinone radical anion UQ.-,
      followed by the rate-determining protonation of this anion with UQH. formation;
      this neutral radical is more easily reduced than UQ, yielding the ubiquinol UQH2.
      In spite of the very low concentration of hydrogen ions as compared with that of
      the acidic component of the buffer, the only effective proton donor is the proton
      itself; this strongly suggests that the protonation step takes place inside the
      polar head region of the DOPC monolayer, which is only accessible to protons.

PMID- 8744310
TI  - Effects of hydrostatic pressure on bilayer phase behavior and dynamics of
      dilauroylphosphatidylcholine.
AB  - Deuterium nuclear magnetic resonance spectroscopy was used to study the
      thermotropic phase behavior of dilauroylphosphatidylcholine (DLPC) bilayers at
      pressures up to 221 MPa. Pressure was found to separate the liquid crystal to gel
      transition from the gel to ordered crystalline phase transition. The jump in
      chain order observed on cooling through the transition into the gel phase was
      found to be small and thus consistent with the trend in longer chain saturated
      diacyl phosphatidylcholines. On cooling, DLPC was observed to enter an unusual
      state above the transition into the gel phase. This unusual state displayed fluid
      like conformational order but short transverse relaxation times. It was found to
      be much better pronounced and to span a broader temperature range at elevated
      pressure than at lower pressures. Transverse relaxation measurements of deuterons
      on the chain alpha-carbons revealed a substantial slowing of molecular motions
      within the temperature range of the unusual fluid phase. The observation of such
      a phase at high pressure appears to be consistent with recent reports of an
      unusual fluid phase, Lx, in DLPC at ambient pressure.

PMID- 8744308
TI  - Activation and inactivation kinetics of an E-4031-sensitive current from single
      ferret atrial myocytes.
AB  - Ferret atrial myocytes can display an E-4031-sensitive current (IKr) that is
      similar to that previously described for guinea pig cardiac myocytes. We examined
      the ferret atrial IKr as the E-4031-sensitive component of current using the
      amphotericin B perforated patch-clamp technique. Steady-state IKr during
      depolarizing pulses showed characteristic inward rectification. Activation time
      constants during a single pulse were voltage dependent, consistent with previous
      studies. However, for potentials positive to +30 mV, IKr time course became
      complex and included a brief transient component. We examined the envelope of
      tails of the drug-sensitive current for activation in the range -10 to +50 mV and
      found that the tail currents for IKr do not activate with the same time course as
      the current during the depolarizing pulse. The activation time course determined
      from tail currents was relatively voltage insensitive over the range +30 to +50
      mV (n = 5), but was voltage sensitive for potentials between -10 and +30 mV and
      appeared to show some sigmoidicity in this range. These data indicate that
      activation of IKr occurs in at least two steps, one voltage sensitive and one
      voltage insensitive, the latter of which becomes rate limiting at positive
      potentials. We also examined the rapid time-dependent inactivation process that
      mediates rectification at positive potentials. The time constants for this
      process were only weakly voltage dependent over the range of potentials from -50
      to +60 mV. From these data we constructed a simple linear four-state model that
      reproduces the general features of ferret IKr, including the initial transient at
      positive potentials and the apparent discrepancy between the currents during the
      initial depolarizing pulse and the tail current.

PMID- 8744312
TI  - Correlation between lipid plane curvature and lipid chain order.
AB  - The 1-palmitoyl-2-oleoyl-phosphatidylethanolamine: 1-palmitoyl-2-oleoyl
      phosphatidylcholine (POPE:POPC) system has been investigated by measuring, in the
      inverted hexagonal (HII) phase, the intercylinder spacings (using x-ray
      diffraction) and orientational order of the acyl chains (using 2H nuclear
      magnetic resonance). The presence of 20 wt% dodecane leads to the formation of a
      HII phase for the composition range from 0 to 39 mol% of POPC in POPE, as
      ascertained by x-ray diffraction and 2H nuclear magnetic resonance. The addition
      of the alkane induces a small decrease in chain order, consistent with less
      stretched chains. An increase in temperature or in POPE proportion leads to a
      reduction in the intercylinder spacing, primarily due to a decrease in the water
      core radius. A temperature increase also leads to a reduction in the
      orientational order of the lipid acyl chains, whereas the POPE proportion has
      little effect on chain order. A correlation is proposed to relate the radius of
      curvature of the cylinders in the inverted hexagonal phase to the chain order of
      the lipids adopting the HII phase. A simple geometrical model is proposed, taking
      into account the area occupied by the polar headgroup at the interface and the
      orientational order of the acyl chains reflecting the contribution of the apolar
      core. From these parameters, intercylinder spacings are calculated that agree
      well with the values determined experimentally by x-ray diffraction, for the
      variations of both temperature and POPE:POPC proportion. This model suggests that
      temperature increases the curvature of lipid layers, mainly by increasing the
      area subtended by the hydrophobic core through chain conformation disorder,
      whereas POPC content affects primarily the headgroup interface contribution. The
      frustration of lipid layer curvature is also shown to be reflected in the acyl
      chain order measured in the L alpha phase, in the absence of dodecane; for a
      given temperature, increased order is observed when the curling tendencies of the
      lipid plane are more pronounced.

PMID- 8744311
TI  - The interfacial structure of phospholipid bilayers: differential scanning
      calorimetry and Fourier transform infrared spectroscopic studies of 1,2
      dipalmitoyl-sn-glycero-3-phosphorylcholine and its dialkyl and acyl-alkyl
      analogs.
AB  - The thermotropic phase behavior of aqueous dispersions of
      dipalmitoylphosphatidylcholine (DPPC) and its 1,2-dialkyl, 1-acyl 2-alkyl and 1
      alkyl 2-acyl analogs was examined by differential scanning calorimetry, and the
      organization of these molecules in those hydrated bilayers was studied by Fourier
      transform infrared spectroscopy. The calorimetric data indicate that substitution
      of either or both of the acyl chains of DPPC with the corresponding ether-linked
      hydrocarbon chain results in relatively small increases in the temperature (< 4
      degrees C) and enthalpy (< 1 kcal/mol) of the lipid chain-melting phase
      transition. The spectroscopic data reveal that replacement of one or both of the
      ester-linked hydrocarbon chains of DPPC with its ether-linked analog causes
      structural changes in the bilayer assembly, which result in an increase in the
      polarity of the local environments of the phosphate headgroups and of the ester
      carbonyl groups at the bilayer polar/apolar interface. The latter observation is
      unexpected, given that ester linkages are considered to be intrinsically more
      polar that ether linkages. This finding cannot be satisfactorily rationalized
      unless the conformation of the glycerol backbones of the analogs containing ether
      linked hydrocarbon chains differs significantly from that of diacyl glycerolipids
      such as DPPC. A comparison of the alpha-methylene scissoring bands and the
      methylene wagging band progressions of these lipids with the corresponding
      absorption bands of specifically chain-perdeuterated analogs of DPPC also
      supports the conclusion that replacement of the ester-linked hydrocarbon chains
      of DPPC with the corresponding ether-linked analog induces conformational changes
      in the lipid glycerol backbone. The suggestion that the conformation of glycerol
      backbones in the alkyl-acyl and dialkyl derivatives of DPPC differs from that of
      the naturally occurring 1,2-diacyl glycerolipid suggests that mono- and di-alkyl
      glycerolipids may not be good models of their diacyl analogs. These results, and
      previously published evidence that DPPC analogs with ether-linked hydrocarbon
      chains spontaneously form chain-interdigitated gel phases at low temperatures,
      clearly indicate that the properties of lipid bilayers can be substantially
      altered by small changes in the chemical structures of their polar/polar
      interfaces, and highlight the critical role of the interfacial region as a
      determinant of the structure and organization of lipid assemblies.

PMID- 8744313
TI  - Long-range tilt orientational order in phospholipid monolayers: a comparative
      study.
AB  - Monolayers of dipalmitoyl-phosphatidyl-N-monomethylethanolamine (DPP(Me)E) and
      dipalmitoyl-phosphatidyl-N,N-dimethylethanolamine (DPP(Me2)E) are studied and
      compared with dipalmitoyl-phosphatidylethanolamine (DPPE), dimyristoyl
      phosphatidylethanolamine (DMPE), and dipalmitoyl-phosphatidylcholine (DPPC) to
      characterize the influence of the headgroup size. The properties of the condensed
      phases of DPP(Me2)E and DPP(Me)E are between those of DPPC and DMPE or DPPE. DPPC
      domains are elongated and the orientation changes continuously, whereas DMPE
      domains are compact and the orientation jumps at curved lines. The domains of
      DPP(Me2)E and DPP(Me)E are compact, and not elongated. The orientation changes
      continuously by 360 degrees around a point in the centered domains, and jumps of
      the orientation occur only in the case of twinning. Furthermore, the size of the
      headgroup influences the erection of the aliphatic chains. For DPPC and
      (DPP(Me2)E), no complete erection of chains occurs, whereas for DPP(Me)E the
      surface pressure required for the complete erection of chains is much higher than
      for DPPE. The same tendency is found for the collapse. DPPC monolayers do not
      collapse. DPP(Me2)E monolayers collapse at a much higher surface pressure than
      those of DPP(Me)E and DPPE.

PMID- 8744314
TI  - Constrained diffusion or immobile fraction on cell surfaces: a new
      interpretation.
AB  - Protein lateral mobility in cell membranes is generally measured using
      fluorescence photobleaching recovery (FPR). Since the development of this
      technique, the data have been interpreted by assuming free Brownian diffusion of
      cell surface receptors in two dimensions, an interpretation that requires that a
      subset of the diffusing species remains immobile. The origin of this so-called
      immobile fraction remains a mystery. In FPR, the motions of thousands of
      particles are inherently averaged, inevitably masking the details of individual
      motions. Recently, tracking of individual cell surface receptors has identified
      several distinct types of motion (Gross and Webb, 1988; Ghosh and Webb, 1988,
      1990, 1994; Kusumi et al. 1993; Qian et al. 1991; Slattery, 1995), thereby
      calling into question the classical interpretation of FPR data as free Brownian
      motion of a limited mobile fraction. We have measured the motion of fluorescently
      labeled immunoglobulin E complexed to high affinity receptors (Fc epsilon RI) on
      rat basophilic leukemia cells using both single particle tracking and FPR. As in
      previous studies, our tracking results show that individual receptors may diffuse
      freely, or may exhibit restricted, time-dependent (anomalous) diffusion.
      Accordingly, we have analyzed FPR data by a new model to take this varied motion
      into account, and we show that the immobile fraction may be due to particles
      moving with the anomalous subdiffusion associated with restricted lateral
      mobility. Anomalous subdiffusion denotes random molecular motion in which the
      mean square displacements grow as a power law in time with a fractional positive
      exponent less than one. These findings call for a new model of cell membrane
      structure.

PMID- 8744315
TI  - Membrane binding of the colicin E1 channel: activity requires an electrostatic
      interaction of intermediate magnitude.
AB  - In vitro channel activity of the C-terminal colicin E1 channel polypeptide under
      conditions of variable electrostatic interaction with synthetic lipid membranes
      showed distinct maxima with respect to pH and membrane surface potential. The
      membrane binding energy was determined from fluorescence quenching of the
      intrinsic tryptophans of the channel polypeptide by liposomes containing N
      trinitrophenyl-phosphatidylethanolamine. Maximum in vitro colicin channel
      activity correlated with an intermediate magnitude of the electrostatic
      interaction. For conditions associated with maximum activity (40% anionic lipid,
      I = 0.12 M, pH 4.0), the free energy of binding was delta G approximately -9
      kcal/mol, with nonelectrostatic and electrostatic components, delta Gnel
      approximately -5 kcal/mol and delta Gel approximately -4 kcal/mol, and an
      effective binding charge of +7 at pH 4.0. Binding of the channel polypeptide to
      negative membranes at pH 8 is minimal, whereas initial binding at pH 4 followed
      by a shift to pH 8 causes only 3-10% reversal of binding, implying that it is
      kinetically trapped, probably by a hydrophobic interaction. It was inferred that
      membrane binding and insertion involves an initial electrostatic interaction
      responsible for concentration and binding to the membrane surface. This is
      followed by insertion into the bilayer driven by hydrophobic forces, which are
      countered in the case of excessive electrostatic binding.

PMID- 8744316
TI  - Effects of alcohols on the phase transition temperatures of mixed-chain
      phosphatidylcholines.
AB  - The biphasic effect of ethanol on the main phase transition temperature (Tm) of
      identical-chain phosphatidyl-cholines (PCs) in excess H2O is now well known. This
      biphasic effect can be attributed to the transformation of the lipid bilayer,
      induced by high concentrations of ethanol, from the partially interdigitated L
      beta, phase to the fully interdigitated L beta I phase at T < Tm. The basic
      packing unit of the L beta I phase has been identified recently as a binary
      mixture of PC/ethanol at the molar ratio of 1:2. The ethanol effect on mixed
      chain PCs, however, is not known. We have thus in this study investigated the
      alcohol effects on the Tm of mixed-chain PCs with different delta C values, where
      delta C is the effective acyl chain length difference between the sn-1 and sn-2
      acyl chains. Initially, molecular mechanics (MM) simulations are employed to
      calculate the steric energies associated with a homologous series of mixed-chain
      PCs packed in the partially and the fully interdigitated L beta I motifs. Based
      on the energetics, the preference of each mixed-chain PC for packing between
      these two different motifs can be estimated. Guided by MM results, high
      resolution differential scanning calorimetry is subsequently employed to
      determine the Tm values for aqueous lipid dispersions prepared individually from
      a series of mixed-chain PCs (delta C = 0.5-6.5 C-C bond lengths) in the presence
      of various concentrations of ethanol. Results indicate that aqueous dispersions
      prepared from mixed-chain PCs with a delta C value of less than 4 exhibit a
      biphasic profile in the plot of Tm versus ethanol concentration. In contrast,
      highly asymmetric PCs (delta C > 4) do not exhibit such biphasic behavior. In the
      presence of a longer chain n-alcohol, however, aqueous dispersions of highly
      asymmetric C(12):C(20)PC (delta C = 6.5) do show such biphasic behavior against
      ethanol. Our results suggest that the delta C region in a highly asymmetric PC
      packed in the L beta I phase is most likely the binding site for n-alcohol.

PMID- 8744317
TI  - Orientation of intermediate nucleotide states of indane dione spin-labeled myosin
      heads in muscle fibers.
AB  - We have used electron paramagnetic resonance to study the orientation of myosin
      heads in the presence of nucleotides and nucleotide analogs, to induce
      equilibrium states that mimic intermediates in the actomyosin ATPase cycle. We
      obtained electron paramagnetic resonance spectra of an indane dione spin label
      (InVSL) bound to Cys 707 (SH1) of the myosin head, in skinned rabbit psoas muscle
      fibers. This probe is rigidly immobilized on the catalytic domain of the head,
      and the principal axis of the probe is aligned nearly parallel to the fiber axis
      in rigor (no nucleotide), making it directly sensitive to axial rotation of the
      head. On ADP addition, all of the heads remained strongly bound to actin, but the
      spectral hyperfine splitting increased by 0.55 +/- 0.02 G, corresponding to a
      small but significant axial rotation of 7 degrees. Adenosine 5'-(adenylylim
      idodiphosphate) (AMPPNP) or pyrophosphate reduced the actomyosin affinity and
      introduced a highly disordered population of heads similar to that observed in
      relaxation. For the remaining oriented population, pyrophosphate induced no
      significant change relative to rigor, but AMPPNP induced a slight but probably
      significant rotation (2.2 degrees +/- 1.6 degrees), in the direction opposite
      that induced by ADP. Adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) relaxed
      the muscle fiber, completely dissociated the heads from actin, and produced
      disorder similar to that in relaxation by ATP. ATP gamma S plus Ca induced a weak
      binding state with most of the actin-bound heads disordered. Vanadate had
      negligible effect in the presence of ADP, but in isometric contraction vanadate
      substantially reduced both force and the fraction of oriented heads. These
      results are consistent with a model in which myosin heads are disordered early in
      the power stroke (weak-binding states) and rigidly oriented later in the power
      stroke (strong-binding states), whereas transitions among the strong-binding
      states induce only slight changes in the axial orientation of the catalytic
      domain.

PMID- 8744318
TI  - Stretch activation and nonlinear elasticity of muscle cross-bridges.
AB  - When active insect fibrillar flight muscle is stretched, its ATPase rate
      increases and it develops "negative viscosity," which allows it to perform
      oscillatory work. We use a six-state model for the cross-bridge cycle to show
      that such "stretch activation" may arise naturally as a nonlinear property of a
      cross-bridge interacting with a single attachment site on a thin filament.
      Attachment is treated as a thermally activated process in which elastic energy
      must be supplied to stretch or compress the cross-bridge spring. We find that
      stretch activation occurs at filament displacements where, before the power
      stroke, the spring is initially in compression rather than in tension. In that
      case, pulling the filaments relieves the initial compression and reduces the
      elastic energy required for attachment. The result is that the attachment rate is
      enhanced by stretching. The model also displays the "delayed tension" effect
      observed in length-step experiments. When the muscle is stretched suddenly, the
      power stroke responds very quickly, but there is a time lag before dissociation
      at the end of the cycle catches up with the increased attachment rate. This lag
      is responsible for the delayed tension and hence also for the negative viscosity.

PMID- 8744319
TI  - Influence of Ca2+ on force redevelopment kinetics in skinned rat myocardium.
AB  - The influence of Ca2+ on isometric force kinetics was studied in skinned rat
      ventricular trabeculae by measuring the kinetics of force redevelopment after a
      transient decrease in force. Two protocols were employed to rapidly detach
      cycling myosin cross-bridges: a large-amplitude muscle length ramp followed by a
      restretch back to the original length or a 4% segment length step. During the
      recovery of force, the length of the central region of the muscle was controlled
      by using a segment marker technique and software feedback control. Tension
      redevelopment was fit by a rising exponential governed by the rate constant ktr
      for the ramp/restretch protocol and kstep for the step protocol. ktr and kstep
      averaged 7.06 s-1 and 15.7 s-1, respectively, at 15 degrees C; neither ktr nor
      kstep increased with the level of Ca2+ activation. Similar results were found at
      submaximum Ca2+ levels when sarcomere length control by laser diffraction was
      used. The lack of activation dependence of ktr contrasts with results from fast
      skeletal fibers, in which ktr varies 10-fold from low to high activation levels,
      and suggests that Ca2+ does not modulate the kinetics of cross-bridge attachment
      or detachment in mammalian cardiac muscle.

PMID- 8744321
TI  - Electrostatic effects on the stability of condensed DNA in the presence of
      divalent cations.
AB  - Cylindrical cell model Poisson-Boltzmann (P-B) calculations are used to evaluate
      the electrostatic contributions to the relative stability of various DNA
      conformations (A, B, C, Z, and single-stranded (ss) with charge spacings of 3.38
      and 4.2 A) as a function of interhelix distance in a concentrated solution of
      divalent cations. The divalent ion concentration was set at 100 mM, to compare
      with our earlier reports of spectroscopic and calorimetric experiments, which
      demonstrate substantial disruption of B-DNA geometry. Monovalent cations
      neutralize the DNA phosphates in two ways, corresponding to different
      experimental situations: 1) There is no significant contribution to the ionic
      strength from the neutralizing cations, corresponding to DNA condensation from
      dilute solution and to osmotic stress experiments in which DNA segments are
      brought into close proximity to each other in the presence of a large excess of
      buffer. 2) The solution is uniformly concentrated in DNA, so that the
      neutralizing cations add significantly to those in the buffer at close DNA
      packing. In case 1), conformations with lower charge density (Z and ssDNA) have
      markedly lower electrostatic free energies than B-DNA as the DNA molecules
      approach closely, due largely to ionic entropy. If the divalent cations bind
      preferentially to single-stranded DNA or a distorted form of B-DNA, as is the
      case with transition metals, the base pairing and stacking free energies that
      stabilize the double helix against electrostatic denaturation may be overcome.
      Strong binding to the bases is favored by the high concentration of divalent
      cations at the DNA surface arising from the large negative surface potential; the
      surface concentration increases sharply as the interhelical distance decreases.
      In case 2), the concentration of neutralizing monovalent cations becomes very
      large and the electrostatic free energy difference between secondary structures
      becomes small as the interhelical spacing decreases. Such high ionic
      concentrations will be expected to modify the stability of DNA by changing water
      activity as well as by screening electrostatic interactions. This may be the root
      of the decreased thermal stability of DNA in the presence of high concentrations
      of magnesium ions.

PMID- 8744322
TI  - Interactions of spermidine and methylspermidine with DNA studied by nuclear
      magnetic resonance self-diffusion measurements.
AB  - The NMR pulsed field gradient self-diffusion method has been used to study the
      self-diffusion of the polyamine spermidine and the polyamine analog
      methylspermidine (completely N-methylated spermidine). The self-diffusion
      coefficient, D, was measured in solutions of calf thymus DNA prepared from
      nucleosome core particles (with an average length of 120 base pairs) as a
      function of the concentration ratio of polyamine to DNA phosphate. A study of the
      self-diffusion quotient, D/Do (where Do is the diffusion coefficient for free
      polyamine, not associated with DNA), in additions of spermidine and methyl
      spermidine to solutions of NaDNA/NaCl, gave almost identical results with
      complete association of polyamine to DNA in the initial part of the titrations,
      indicating similar affinities for DNA. A large influence on the measured self
      diffusion coefficients was detected for methylspermidine in NaDNA solutions with
      different concentrations of NaCl, which shows a considerable salt effect on the
      polyamine-DNA association. No notable differences in D/Do for methylspermidine
      were observed in competitive titrations of solutions of Li- and NaDNA, indicating
      that sodium and lithium ions behave similarly in their interactions with DNA. In
      titration experiments of methylspermidine into MgDNA solution, the results showed
      that the polyamine association is less effective than in the case of NaDNA,
      because of competition from magnesium binding to DNA. Comparisons with
      calculations based on the electrostatic Poisson-Boltzmann cell model were
      performed. It is suggested that the interaction is primarily of electrostatic
      nature, with no binding to specific sites on the DNA molecule.

PMID- 8744320
TI  - Osmotic pressure probe of actin-myosin hydration changes during ATP hydrolysis.
AB  - Osmotic stress in the 0.5-5 x 10(6) dyne/cm2 range was used to perturb the
      hydration of actin-myosin-ATP intermediates during steady-state hydrolysis.
      Polyethylene glycol (PEG) (1000 to 4000 Da), in the 1 to 10 wt% range, which does
      not cause protein precipitation, did not significantly affect the apparent KM or
      the Vmax for MgATP hydrolysis by myosin subfragment 1 (S1) alone, nor did it
      affect the value for the phosphate burst. Consistent with the kinetic data,
      osmotic stress did not affect nucleotide-induced changes in the fluorescence
      intensities of S1 tryptophans or of fluorescein attached to Cys-707. The
      accessibility of the fluorescent ATP analog, epsilon ADP, to acrylamide quenching
      was also unchanged. These data suggest that none of the steps in the ATP
      hydrolysis cycle involve substantial hydration changes, which might occur for the
      opening or closing of the ATP site or of other crevices in the S1 structure. In
      contrast, KM for the interaction of S1.MgADP.Pi with actin decreased tenfold in
      this range of osmotic pressure, suggesting that formation of actin.S1.MgADP.Pi
      involves net dehydration of the proteins. The dehydration volume increases as the
      size of the PEG is increased, as expected for a surface-excluded osmolyte. The
      measured dehydration volume for the formation of actin.S1.MgADP.Pi was used to
      estimate the surface area of the binding interface. This estimate was consistent
      with the area determined from the atomic structures of actin and myosin,
      indicating that osmotic stress is a reliable probe of actin.myosin.ATP
      interactions. The approach developed here should be useful for determining
      osmotic stress and excluded volume effects in situ, which are much larger than
      those of typical in vitro conditions.

PMID- 8744323
TI  - Crystal structure of the B-DNA hexamer d(CTCGAG): model for an A-to-B transition.
AB  - The crystal structure of the B-DNA hexamer d(CTCGAG) has been solved at 1.9 A
      resolution by iterative single isomorphous replacement, using the brominated
      derivative d(CG5BrCGAG), and refined to an R-factor of 18.6% for 120 nonhydrogen
      nucleic acid atoms and 32 water molecules. Although the central four base pairs
      form a typical B-form helix, several parameters suggest a transition to an A-like
      conformation at the termini. Based on this observation, a B-to-A transition was
      modeled, maintaining efficient base stacking across the junction. The wide minor
      groove (approximately 6.9 A) is reminiscent of that in the side-by-side double
      drug-DNA complexes and hosts a double spine of hydration. The global helix axes
      of the pseudo-continuous helices are at an acute angle of 60 degrees. The
      pseudocontinuous stacking is reinforced by the minor groove water structure
      extending between the two duplexes. The crossover point of two pairs of stacked
      duplexes is at the stacking junction, unlike that observed in the B-DNA decamers
      and dodecamers. This arrangement may have implications for the structure of a
      four-way DNA junction. The duplexes are arranged around a large (approximately 20
      A diameter) channel centered on a 6(2) screw axis.

PMID- 8744324
TI  - Measurement of intercolumnar forces between parallel guanosine four-stranded
      helices.
AB  - The deoxyguanosine-5'-monophosphate in aqueous solution self-associates into
      stable structures, which include hexagonal and cholesteric columnar phases. The
      structural unit is a four-stranded helix, composed of a stacked array of
      Hoogsteen-bonded guanosine quartets. We have measured by osmotic stress method
      the force per unit length versus interaxial distance between helices in the
      hexagonal phase under various ionic conditions. Two contributions have been
      recognized: the first one is purely electrostatic, is effective at large
      distances, and shows a strong dependence on the salt concentration of the
      solution. The second contribution is short range, dominates at interaxial
      separations smaller than about 30-32 A, and rises steeply as the columns approach
      each other, preventing the coalescence of the helices. This repulsion has an
      exponential nature and shows a magnitude and a decay length insensitive to the
      ionic strength of the medium. Because these features are distinctive of the
      hydration force detected between phospholipid bilayers or between several linear
      macromolecules (DNA, polysaccharides, collagen), we conclude that the dominant
      force experienced by deoxyguanosine helices approaching contact is hydration
      repulsion. The observed decay length of about 0.7 A has been rationalized to
      emerge from the coupling between the 3-A decay length of water solvent and the
      helically ordered structure of the hydrophilic groups on the opposing surfaces.
      The present results agree with recent measurements, also showing the dependence
      of the hydration force decay on the structure of interacting surfaces and confirm
      the correlations between force and structure.

PMID- 8744325
TI  - Replacement effects of neutral amino acid residues of different molecular volumes
      in the retinal binding cavity of bacteriorhodopsin on the dynamics of its primary
      process.
AB  - We have determined the rate and quantum yield of retinal photoisomerization, the
      spectra of the primary transients, and the energy stored in the K intermediate in
      the photocycle of some bacteriorhodopsin mutants (V49A, A53G, and W182F) in which
      residue replacements are found to change the Schiff base deprotonation kinetics
      (and thus the protein-retinal interaction). Because of their change in the local
      volume resulting from these individual replacements, these substitutions perturb
      the proton donor-acceptor relative orientation change and thus the Schiff base
      deprotonation kinetics. These replacements are thus expected to change the charge
      distribution around the retinal, which controls its photoisomerization dynamics.
      Subpicosecond transient spectroscopy as well as photoacoustic technique are used
      to determine the retinal photoisomerization rate, quantum yield, and the energy
      stored in the K-intermediate for these mutants. The results are compared with
      those obtained for wild-type bacteriorhodopsin and other mutants in which charged
      residues in the cavity are replaced by neutral ones. In some of the mutants the
      rate of photoisomerization is changed, but in none is the quantum yield or the
      energy stored in the K intermediate altered from that in the wild type. These
      results are discussed in terms of the shapes of the potential energy surfaces of
      the excited and ground states of retinal in the perpendicular configuration
      within the protein and the stabilization of the positive charge in the ground and
      the excited state of the electronic system of retinal.

PMID- 8744326
TI  - Analysis of conformational changes in bacteriorhodopsin upon retinal removal.
AB  - The conformation of bacterioopsin in the apomembrane has been studied by Fourier
      transform infrared spectroscopy. Resolution enhancement techniques and curve
      fitting procedures have been used to determine the secondary structural
      components from the amide I region. Bacterioopsin contains about 54% helicoidal
      structure (alpha I and alpha II helices + 3(10) turns), 21% sheets, 16% reverse
      turns, and 9% unordered structure. Thus, after retinal removal, all of the
      secondary structural types of bacteriorhodopsin remain present, and only slight
      quantitative differences appear. On the other hand, H/D exchange studies show
      that there is a higher degree of exchange for reverse turns and protonated
      carboxylic lateral chains in bacterioopsin as compared to bacteriorhodopsin. This
      gives further support to the idea of a more open tertiary structure of
      bacterioopsin, and to the consideration of the retinal molecule as an important
      element in complementing the interhelical interactions in bacteriorhodopsin
      folding.

PMID- 8744327
TI  - Simulations of reversible protein aggregate and crystal structure.
AB  - We simulated the structure of reversible protein aggregates as a function of
      protein surface characteristics, protein-protein interaction energies, and the
      entropic penalty accompanying the immobilization of protein in a solid phase.
      These simulations represent an extension of our previous work on kinetically
      irreversible protein aggregate structure and are based on an explicit accounting
      of the specific protein-protein interactions that occur within reversible
      aggregates and crystals. We considered protein monomers with a mixture of
      hydrophobic and hydrophilic surface regions suspended in a polar solvent; the
      energetic driving force for aggregation is provided by the burial of solvent
      exposed hydrophobic surface area. We analyzed the physical properties of the
      generated aggregates, including density, protein-protein contact distributions,
      solvent accessible surface area, porosity, and order, and compared our results
      with the protein crystallization literature as well as with the kinetically
      irreversible case. The physical properties of reversible aggregates were
      consonant with those observed for the irreversible aggregates, although in
      general, reversible aggregates were more stable energetically and were more
      crystal-like in their order content than their irreversible counterparts. The
      reversible aggregates were less dense than the irreversible aggregates,
      indicating that the increased energetic stability is derived primarily from the
      optimality rather than the density of the packing in the solid phase. The extent
      of hydrophobic protein-protein contacts and solvent-exposed surface area within
      the aggregate phase depended on the aggregation pathway: reversible aggregates
      tended to have a greater proportion of hydrophobic-hydrophobic contacts and a
      smaller fraction of hydrophobic solvent-exposed surface area. Furthermore, the
      arrangement of hydrophobic patches on the protein surface played a major role in
      the distribution of protein contacts and solvent content. This was readily
      reflected in the order of the aggregates: the greater the contiguity of the
      hydrophobic patches on the monomer surface, the less ordered the aggregates
      became, despite the opportunities for rearrangement offered by a reversible
      pathway. These simulations have enhanced our understanding of the impact of
      protein structural motifs on aggregate properties and on the demarcation between
      aggregation and crystallization.

PMID- 8744328
TI  - Probing pH and pressure effects on the apomyoglobin heme pocket with the 2'-(N,N
      dimethylamino)-6-naphthoyl-4-trans-cyclohexanoic acid fluorophore.
AB  - The environmentally sensitive fluorophore 2'-(N,N-dimethylamino)-6-naphthoyl-4
      trans-cyclohexanoic acid (DANCA) has been used to probe the apomyoglobin heme
      pocket. The unexpected polarity of this domain is generally interpreted as
      arising from dynamic dipolar relaxation of the peptide dipoles surrounding the
      heme pocket. In the present work we reexamine the photophysical properties of
      DANCA in a variety of solvents and complexed with apomyoglobin (apoMb) to further
      probe the heme pocket environment as a function of external solvent conditions.
      Absorption and excitation spectra in a number of solvents are consistent with the
      well-known pi*<--pi (LE) and pi*<--n (CT) electronic absorption transitions
      observed for naphthylamine derivatives. Dual emission is also a well-documented
      property of such derivatives. Based on the time scale of the heterogeneity in the
      decay of the DANCA fluorophore observed in a series of solvents, we propose that
      the emission properties of DANCA in apoMb are not uniquely attributable to
      dynamic relaxation events, but also reflect dual emission from both a long-lived,
      red CT state and the shorter-lived, blue LE state. The pH studies in the range of
      pH 5-9 of the emission properties of DANCA in apoMb support this hypothesis. They
      also suggest a specific interaction of DANCA with one or both of the pocket
      histidyl residues, which leads to a drastic static quenching and red shift of the
      bound DANCA fluorescence upon protonation. Similar effects are observed with
      increasing pressure, indicating that these two perturbations alter the DANCA
      apoMb complex in a similar fashion. The pressure-induced form of the protein is
      distinct both energetically and structurally from the previously characterized
      acid intermediate, in that it is populated above pH 5 and retains a significant
      degree of integrity of the heme pocket.

PMID- 8744329
TI  - The effects of weak extremely low frequency magnetic fields on calcium/calmodulin
      interactions.
AB  - Mechanisms by which weak electromagnetic fields may affect biological systems are
      of current interest because of their potential health effects. Lednev has
      proposed an ion parametric resonance hypothesis (Lednev, 1991,
      Bioelectromagnetics, 12:71-75), which predicts that when the ac, frequency of a
      combined dc-ac magnetic field equals the cyclotron frequency of calcium, the
      affinity of calcium for calcium-binding proteins such as calmodulin will be
      markedly affected. The present study evaluated Lednev's theory using two
      independent systems, each sensitive to changes in the affinity of calcium for
      calmodulin. One of the systems used was the calcium/calmodulin-dependent
      activation of myosin light chain kinase, a system similar to that previously used
      by Lednev. The other system monitored optical changes in the binding of a
      fluorescent peptide to the calcium/calmodulin complex. Each system was exposed to
      a 20.9 microT static field superimposed on a 20.9 microT sinusoidal field over a
      narrow frequency range centered at 16 Hz, the cyclotron frequency of the
      unhydrated calcium ion. In contrast to Lednev's predictions, no significant
      effect of combined dc-ac magnetic fields on calcium/calmodulin interactions was
      indicated in either experimental system.

PMID- 8744330
TI  - Near-infrared spectra of Scapharca homodimeric hemoglobin: characterization of
      the deoxy and photodissociated derivatives.
AB  - The near-infrared charge transfer band at 760 nm (band III) has been investigated
      in deoxy and photodissociated dimeric Scapharca hemoglobin. At 300 K, the 10-ns
      spectrum of the carbonmonoxy derivative photoproduct is shifted by about 6 nm
      toward longer wavelengths with respect to the deoxy spectrum, both in buffer and
      in glycerol/buffer solutions. Moreover, the band III peak occurs at about the
      same wavelength at 300 K and at 10 K for the 10-ns photodissociated derivative,
      whereas in the deoxy derivative large changes in peak position and linewidth are
      observed as a function of temperature. These findings suggest that in dimeric
      Scapharca hemoglobin the photoproduct has not relaxed after 10 ns. The complete
      time dependence of the relaxation process has been studied both in buffer and in
      glycerol/buffer solutions at room temperature. The relaxation from the
      photoproduct to the deoxy species occurs on a microsecond time scale, in line
      with recent optical absorption and resonance Raman measurements.

PMID- 8744331
TI  - Binding of bovine factor Va to phosphatidylcholine membranes.
AB  - The interaction of bovine factor Va with phosphatidylcholine membranes was
      examined using four different fluorescence techniques: 1) changes in the
      fluorescence anisotropy of the fluorescent membrane probe 1,6-diphenyl-1,3,5
      hexatriene (DPH) to monitor the interaction of factor Va with 1,2-dimyristoyl-3
      sn-phosphatidylcholine (DMPC) small unilamellar vesicles (SUVs), 2) changes in
      the fluorescence anisotropy of N-(lissamine rhodamine B sulfonyl) diacyl
      phosphati-dylethanolamine (Rh-PE) incorporated into SUVs prepared from 1
      palmitoyl-2-oleoyl-3-sn-phosphatidylcholine (POPC), 3) changes in the
      fluorescence anisotropy of fluorescein-labeled factor Va (labeled in the heavy
      chain) upon interaction with POPC SUVs, 4) fluorescence energy transfer from
      fluorescein-labeled factor Va to rhodamine-labeled POPC SUVs. In the first two
      sets of experiments, labeled lipid vesicles were titrated with unlabeled protein,
      whereas, in the latter two types of experiments, labeled factor Va was titrated
      with vesicles. For the weak binding observed here, it was impossible from any one
      binding experiment to obtain precise estimates of the three parameters involved
      in modeling the lipid-protein interaction, namely, the dissociation constant Kd,
      the stoichiometry of binding i, and the saturation value of the observable Rmax
      from any one experiment. However, a global analysis of the four data sets
      involving POPC SUVs yielded a stable estimate of the binding parameters (Kd of
      approximately 3.0 microM and a stoichiometry of approximately 200 lipids per
      bound factor Va). Binding to DMPC SUVs may be of slightly higher affinity. These
      observations support the contention that association of factor Va with a membrane
      involves a significant acidic-lipid-independent interaction along with the more
      commonly accepted acidic-lipid-dependent component of the total binding free
      energy.

PMID- 8744332
TI  - Insights into the complex association of bovine factor Va with acidic-lipid
      containing synthetic membranes.
AB  - The mechanism of binding of blood coagulation cofactor factor Va to acidic-lipid
      containing membranes has been addressed. Binding isotherms were generated at room
      temperature using the change in fluorescence anisotropy of pyrene-labeled bovine
      factor Va to detect binding to sonicated membrane vesicles containing either
      bovine brain phosphatidylserine (PS) or 1,2-dioleoyl-3-sn-phosphatidylglycerol
      (DOPG) in combination with 1-palmitoyl-2-oleoyl-3-sn-phosphatidylcholine (POPC).
      The composition of the membranes was varied from 0 to 40 mol% for PS/POPC and
      from 0 to 65 mol % for DOPG/POPC membranes. Fitting the data to a classical
      Langmuir adsorption model yielded estimates of the dissociation constant (Kd) and
      the stoichiometry of binding. The values of Kd defined in this way displayed a
      maximum at low acidic lipid content but were nearly constant at intermediate to
      high fractions of acidic lipid. Fitting the binding isotherms to a two-process
      binding model (nonspecific adsorption in addition to binding of acidic lipids to
      sites on the protein) suggested a significant acidic-lipid-independent binding
      affinity in addition to occupancy of three protein sites that bind PS in
      preference to DOPG. Both analyses indicated that interaction of factor Va with an
      acidic-lipid-containing membrane is much more complex than those of factor Xa or
      prothrombin. Furthermore, a change in the conformation of bound pyrene-labeled
      factor Va with surface concentration of acidic lipid was implied by variation of
      both the saturating fluorescence anisotropy and the binding parameters with the
      acidic lipid content of the membrane. Finally, the results cannot support the
      contention that binding occurs through nonspecific adsorption to a patch or
      domain of acidic lipids in the membrane. Factor Va is suggested to associate with
      membranes by a complex process that includes both acidic-lipid-specific and
      acidic-lipid-independent sites and a protein structure change induced by
      occupancy of acidic-lipid-specific sites on the factor Va molecule.

PMID- 8744333
TI  - Anomalous diffusion of water in biological tissues.
AB  - This article deals with the characterization of biological tissues and their
      pathological alterations. For this purpose, diffusion is measured by NMR in the
      fringe field of a large superconductor with a field gradient of 50 T/m, which is
      rather homogenous and stable. It is due to the unprecedented properties of the
      gradient that we are able not only to determine the usual diffusion coefficient,
      but also to observe the pronounced Non-Debye feature of the relaxation function
      due to cellular structure. The dynamics of the probability density follow a
      stretched exponential or Kohlrausch-Williams-Watts function. In the long time
      limit the Fourier transform of the probability density follows a long-tail Levy
      function, whose asymptotic is related to the fractal dimension of the underlying
      cellular structure. Some of the properties of Levy walk statistics are discussed
      and its potential importance in understanding certain biophysical phenomena like
      diffusion processes in biological tissues are pointed out. We present and discuss
      for the first time NMR data giving evidence for Levy processes that capture the
      essential features of the observed power law (scaling) dynamics of water
      diffusion in fresh tissue specimens: carcinomas, fibrous mastopathies, adipose
      and liver tissues.

PMID- 8744334
TI  - Influence of the triplet excited state on the photobleaching kinetics of
      fluorescein in microscopy.
AB  - The investigation in this report aimed at providing photophysical evidence that
      the long-lived triplet excited state plays an important role in the non-single
      exponential photobleaching kinetics of fluorescein in microscopy. Experiments
      demonstrated that a thiol-containing reducing agent, mercaptoethylamine (MEA or
      cysteamine), was the most effective, among other commonly known radical quenchers
      or singlet oxygen scavengers, in suppressing photobleaching of fluorescein while
      not reducing the fluorescence quantum yield. The protective effect against
      photobleaching of fluorescein in the bound state was also found in microscopy.
      The antibleaching effect of MEA let to a series of experiments using time-delayed
      fluorescence spectroscopy and nanosecond laser flash photolysis. The combined
      results showed that MEA directly quenched the triplet excited state and the
      semioxidized radical form of fluorescein without affecting the singlet excited
      state. The triplet lifetime of fluorescein was reduced upon adding MEA. It
      demonstrated that photobleaching of fluorescein in microscopy is related to the
      accumulation of the long-lived triplet excited state of fluorescein and that by
      quenching the triplet excited state and the semioxidized form of fluorescein to
      restore the dye molecules to the singlet ground state, photobleaching can be
      reduced.

PMID- 8744336
TI  - Thermodynamic response of soft biological tissues to pulsed infrared-laser
      irradiation.
AB  - The physical mechanisms that achieve tissue removal through the delivery of short
      pulses of high-intensity infrared laser radiation, in a process known as laser
      ablation, remain obscure. The thermodynamic response of biological tissue to
      pulsed infrared laser irradiation was investigated by measuring and analyzing the
      stress transients generated by Q-sw Er:YSGG (lambda = 2.79 microns) and TEA CO2
      (lambda = 10.6 microns) laser irradiation of porcine dermis using thin-film
      piezoelectric transducers. For radiant exposures that do not produce material
      removal, the stress transients are consistent with thermal expansion of the
      tissue samples. The temporal structure of the stress transients generated at the
      threshold radiant exposure for ablation indicates that the onset of material
      removal is delayed with respect to irradiation. Once material removal is
      achieved, the magnitude of the peak compressive stress and its variation with
      radiant exposure are consistent with a model that considers this process as an
      explosive event occurring after the laser pulse. This mechanism is different from
      ArF- and KrF-excimer laser ablation where absorption of ultraviolet radiation by
      the collagenous tissue matrix leads to tissue decomposition during irradiation
      and results in material removal via rapid surface vaporization. It appears that
      under the conditions examined in this study, explosive boiling of tissue water is
      the process that mediates the ablation event. This study provides evidence that
      the dynamics and mechanism of tissue ablation processes can be altered by
      targeting tissue water rather than the tissue structural matrix.

PMID- 8744335
TI  - Orientation-dependent visibility of long thin objects in polarization-based
      microscopy.
AB  - Under conditions of directional illumination, the visibility of long, thin
      objects depends very strongly on the direction and polarization of the incident
      light. Solutions to Maxwell's equations for the case of an infinite cylinder in
      an electromagnetic field are well known, and have been used by others in the past
      for theoretical analysis of light scattering by long, thin objects. The existence
      of those solutions allows us to calculate the expected angular distribution and
      polarization of the light scattered from long, thin objects illuminated by a
      plane wave at any angle. In this paper we show for the first time how one can
      incorporate these solutions of Maxwell's equations into a quantitative
      description of the expected appearance of filamentous biological structures in
      polarization-based microscopy. Our calculations for unidirectional polarized
      illumination show that thin, dielectric linear objects such as microtubules (or
      shallow interfaces) observed with finite aperture optics 1) are totally invisible
      when the angle (phi) between the object's long axis and incident illumination is
      outside the range magnitude of 90 - phi < or = sin-1 [1.33/N.A.obj]degrees; and
      2) are seen with maximum intensity when phi = 90 degrees for incident
      illumination and scattered light polarized, either both parallel or both
      perpendicular to the long axis of the object; whereas 3) two maxima appear at phi
      approximately equal to 90 +/- 25 degrees for polarization of the incident
      illumination parallel to, but the scattered light perpendicular to the long axis,
      or vice versa; and 4) in either of these latter conditions, the objects are
      invisible when the illumination is near normal incidence. These counterintuitive
      predictions were exactly borne out by our experimental measurements of light
      scattering intensity from flagellar axonemes as a function of orientation in a
      polarizing microscope. These calculations and measurements provide a foundation
      for furthering our understanding of textural or form birefringence. Calculations
      based on a solid cylinder model accurately predict the shapes of the measured
      intensity versus orientation curves. However, the relative intensities of
      axonemes viewed with different polarizer-analyzer settings differ from those
      calculated for a homogeneous solid cylinder. Thus we find that these relative
      intensities can provide a sensitive probe for the structure of biological objects
      with diameters much smaller than the wavelength of light.

PMID- 8744337
TI  - Archival journal requirements for data deposition.

PMID- 8744338
TI  - [Unflagging attention to the military component of medical service].
AB  - The article analyzes the causes of unsettled problems of troops elements of
      medical service, the directions toward optimization of there function. The most
      important factors of the effective work of troops elements of medical service are
      prophylaxis of widespread diseases, traumas and poisoning among Army and Navy
      personnel, strengthening of the sanitary epidemiologic control, early and active
      diagnosis, improvement of the prophylactic medical examination, quality increase
      of diagnosis and treatment activities. Is emphasized that up to 80% of ill
      servicemen must complete there stationary treatment in the troops medical
      institutions. From the point of health protection of servicemen the practical
      importance of medical post as a centre of diagnosis and treatment in troops is
      increasing, its readiness to provide emergency medical care in any conditions is
      growing too. Is given attention to necessity to re-equip the medical service of
      airborne troops, forming the main part of the Mobile Forces, with mobile medical
      complex, to increase quantity of providing medical care in the units, to
      reconsider the structure of troops medical staff, to expand it by surgeons and
      medical personnel.

PMID- 8744339
TI  - [The tasks in maintaining and strengthening the mental health of servicemen].
AB  - The state of medical psychiatric service and the outlook for its improvement in
      Armed Forces of Russian Federation have been analyzed. In peace time it is
      reasonable to organize medical psychological and psychiatric care to military men
      with border disorders, to psychosomatic patients and also to really healthy men,
      who are in critical situation, to elaborate a new organized structure of staff,
      providing psychoprophylactic care. During war conflicts it is important to
      foresee in forward zone the corrective activities and treatment of patients with
      psychological stress reactions and addict disorders, to provide the wounded with
      psychiatric correction and care.

PMID- 8744341
TI  - [Emergency medical care at the prehospital stage].

PMID- 8744340
TI  - [The problems of preventing tuberculosis in the Armed Forces].

PMID- 8744342
TI  - [The prevention of gynecologic diseases in servicewomen in the troop unit and at
      the prehospital stage].
AB  - The article determines the main tasks of health maintaining and strengthening of
      service-women. These tasks assume medical supervision before enrollment in the
      army, creation of the necessary living conditions, sanitary gynecologic teaching,
      early active diagnosis and treatment of gynecologic diseases, prophylactic
      dynamic medical examination of the patients.

PMID- 8744343
TI  - [Local oxygenation of the area of a gunshot fracture in treating those with
      extremity wounds].

PMID- 8744344
TI  - [The characteristics of drainage after operations on the brain].
AB  - The article discusses the actual problems of surgical wounds drainage in
      different brain diseases and traumas associated with brain illness. The processes
      occurring in surgical brain wound are analyzed: edema, swelling, hemorrhage,
      local immune reactions, difficult venous outflow, hyperproduction of liquor.
      Demands of cerebral wounds drainage are substantiated.

PMID- 8744346
TI  - [The use of protein preparations in the combined treatment of pneumonia
      patients].

PMID- 8744345
TI  - [The prospects for using knee joint arthroscopy in military hospitals].
AB  - The authors described personal experience performing 263 knee joint arthroscopies
      in military medical institutions. It allowed them to improve the diagnosis of
      joint diseases and lesions and to increase its accuracy up to 92%. Four levels of
      endoscopist's competence defining the accuracy of diagnostic and quality of
      surgical joint arthroscopy was distinguished. It was determined that knee
      arthroscopy in servicemen has a great importance in meniscus pathology to define
      the indications to arthrotomy and to choice rational surgical access. Thus,
      diagnostic accuracy is 88%. In the knee joint gunshot injuries it is reasonable
      to fulfil arthroscopy with medicative purpose to ablate intra-articular foreign
      bodies and also for sanitation and drainage of its cavity.

PMID- 8744347
TI  - [The comparative characteristics of nutrient mixtures in the artificial
      therapeutic feeding of patients].

PMID- 8744348
TI  - [Modern methods and means for the rapid determination of the sensitivity of the
      causative agents of dangerous infectious diseases to antibiotics and chemical
      preparations].

PMID- 8744349
TI  - [The organization of medical care in overcooling in seawater].

PMID- 8744351
TI  - The puzzling origin of the genetic code.
AB  - Recent results add to the mystery of the origin of the genetic code. In spite of
      early doubts, RNA can discriminate between hydrophobic amino acids under certain
      contexts. Moreover, codon reassignment, which has taken place in several
      organisms and mitochondria, is not a random process. Finally, phylogenies of some
      aminoacyl-tRNA synthetases suggest that the entire code was not completely
      assigned at the time of the divergence of bacteria from nucleated cells.

PMID- 8744350
TI  - Catastrophic revelations about Op18/stathmin.

PMID- 8744352
TI  - A new significant recurrent dyad pairing in Haemophilus influenzae.

PMID- 8744354
TI  - Does this have a familiar RING?
AB  - The RING finger is a zinc-binding domain that is found in proteins from plants to
      humans, but whose function remains largely enigmatic. The domain itself is
      distinct from other zinc-finger motifs in terms of sequence homology, zinc
      ligation scheme and three-dimensional structure. It appears that the RING is
      involved in mediating protein-protein interactions and in some cases multi
      protein complexes, which might depend on the presence of other proteins and/or
      domains.

PMID- 8744353
TI  - Knowing when not to stop: selenocysteine incorporation in eukaryotes.
AB  - The regulation of translation frequently involves protein-RNA interactions. An
      intriguing example of this is the alternative decoding of UGA, typically a stop
      codon, as selenocysteine. Two RNA structures, the mRNA selenocysteine insertion
      sequence (SECIS element) and a unique selenocysteyl-tRNA, are required for this
      process. In prokaryotes, a single RNA-binding protein, a selenocysteine-specific
      elongation factor, interacts with both the tRNA and mRNA to confer decoding.
      Whether eukaryotes use a similar mechanism is currently the subject of intense
      investigation.

PMID- 8744355
TI  - Quorum sensing: a population-density component in the determination of bacterial
      phenotype.
AB  - In bacteria, a network of cellular transduction mechanisms integrate signals from
      the bacterial environment to control gene expression, and thereby the bacterial
      phenotype. 'Quorum sensing' describes one such signalling mechanism in response
      to population density. It relies on the accumulation of small extracellular
      signalling molecules to modulate the transcription of target operons.

PMID- 8744356
TI  - Ribozymes: structure and mechanism in RNA catalysis.
AB  - The hammerhead RNA is a small catalytic RNA found in a number of RNA virus
      genomes and virus-like RNAs. The recently determined crystal structures of
      hammerhead ribozymes reveal how a small RNA motif can fold up into a conformation
      suitable for mediating RNA cleavage.

PMID- 8744359
TI  - The maddening business of King George III and porphyria.

PMID- 8744358
TI  - A dynamic look at structures: WWW-Entrez and the Molecular Modeling Database.

PMID- 8744357
TI  - Carriers for precipitating nucleic acids.
AB  - Methods and reagents is a unique monthly column that highlights current
      discussions in the newsgroup bionet.molbio.methds-reagnts, available on the
      Internet. This month's column provides some tips for the precipitation of DNA and
      RNA samples. For details on how to partake in the newsgroup, see the accompanying
      box.

PMID- 8744360
TI  - [Dynamics of population waves in a heterogeneous predator-prey system using the
      example of interaction of waves formed by Dictyostelium discoideum amoeba and a
      spatially distributed population of immobilized Escherichia coli cells].

PMID- 8744361
TI  - [Inhibition of human immunodeficiency virus replication by anionic dyes].

PMID- 8744362
TI  - [Sharp increase in proliferating activity in generations of tumor cells surviving
      after high doses of radiation].

PMID- 8744363
TI  - [Alpha-2-adrenergic receptors of the chick embryo amnion].

PMID- 8744365
TI  - [Kaposi's sarcoma: an infectious disease?].

PMID- 8744364
TI  - [Effect of dilantin on retardation of cortex neuronal activity during interaction
      of extraneous stimuli and the dominant status of the defense reflex].

PMID- 8744366
TI  - [Pleural tuberculosis: analysis of 105 cases].
AB  - BACKGROUND: We present the results of a retrospective study with patients
      diagnosed of tuberculous pleuritis (TP) to offer a view and a perspective of this
      entity in our area. METHODS: We reviewed 105 cases of TP according to age,
      tuberculous risk factors, clinical onset, tuberculin test, chest roentgenogram,
      pleural fluid analysis (ADA, LDH, glucose and proteins) and pleural biopsy, and
      the evolution or sequels of the pleural effusion after a specific treatment.
      RESULTS: TP was a disease of younger patients (62% less than 30 years old) with
      tuberculous risk factors (34.3%), positive tuberculin test (81%) and an acute or
      subacute onset (88.5%). The pleural effusion was unilateral (98.1%), small-sized
      (61%), with pulmonary infiltrates in the 22.4%. All of the effusions were
      exudates with the exception of a transudative case. The levels of LDH, glucose
      and ADA were increased and the white cell counts below 6000/mm2, predominantly
      mononuclear. ADA was below 40 U/L in the 17% of cases. Pleural biopsy established
      the diagnosis in the 92.2% and the diagnosis was obtained in the 98.6% when we
      associated the analysis of ADA, pleural fluid and pleural biopsy. Specific
      treatment was accompanied with a good response. CONCLUSIONS: Our findings
      supported that TP maintained the predilection for younger patients with
      tuberculous risk factors. The clinical onset, radiographies, pleural fluid
      analysis and the utility of all diagnostic examinations were similar to other
      previous studies with the exception of few atypical cases. We confirmed a good
      prognosis with a correct treatment.

PMID- 8744368
TI  - [Pneumocystis carinii pneumonia in the transplant recipient].
AB  - BACKGROUND: The aim of the present was to study the clinical characteristics and
      prognostic factors of 20 cases of pneumonia by Pneumocystis carinii (NPC)
      diagnosed over the last 10 years in renal, renopancreatic, liver and bone marrow
      transplant recipients. METHODS: The clinical histories of all the patients
      transplanted in the authors' hospital from 1985 to 1994 who developed NPC were
      analyzed. Diagnosis was established by visualization of cysts in methenamine
      silver staining of bronchialveolar lavage (BAL) samples. RESULTS: The global
      incidence of NPC in our transplant population was 1%. However, the incidence was
      3% in the recipients who did not receive prophylaxis. No patient in this series
      received prophylaxis at the time of diagnosis. Ninety percent of the patients had
      history or rejection. Pneumonia was observed in 15 (75%) in the first 6 months
      post transplantation. The mean length of the symptoms prior to diagnosis was 10
      days. Ninety-five percent of the patients presented cough, dysnea and fever.
      Radiology demonstrated diffuse alveolointerstitial infiltrates in 18 patients
      (90%). Basal arterial PO2 was lower than 60 mmHg in 14 (70%) patients and the
      alveoloarterial gradient of oxygen was greater than 60 mmHg in 9 (45%).
      Mechanical ventilation was required in 50% of the patients. BAL demonstrated
      cytologic alterations compatible with CMV infection in 50% of the cases and in
      two Aspergillus fumigatus was associated. Mortality was 35%. The only variable
      significantly associated with bad prognosis was the need for mechanical
      ventilation (p = 0.003). CONCLUSIONS: The incidence of pneumonia by P. carinii in
      a population of transplant recipients was 1%. No patient received primary
      prophylaxis at the time of diagnosis. Most of the episodes were observed during
      the first 6 months post transplant. Mortality was 35% with the only variable with
      prognostic significance being the need for mechanical ventilation.

PMID- 8744367
TI  - [Analysis of 1,187 consecutive cases of AIDS: variations and trends in time].
AB  - BACKGROUND: The characteristics of AIDS patients in Spain have already been
      described, as have the factors which may or may not be present at the time of
      AIDS diagnosis influence in the prognosis. The introduction of zidovudine and
      later other antiretroviral drugs have improved the prognosis versus historical
      controls. Nonetheless, advances in prevention, control and the treatment of
      opportunistic infections have provided the greatest influence in the development
      of clinical manifestations of AIDS: The aim of the present was to study the
      evolution of AIDS patients seen at the Hospital Clinic in Barcelona, Spain, from
      1985 to 1992 and analyze the variations in the time of clinical manifestations
      and survival. METHODS: The clinical records of 1187 patients in the Hospital
      Clinic in Barcelona with HIV infection who developed AIDS (1985-1992) according
      to the CDC criteria of August 1987 were retrospectively reviewed. RESULTS: Out of
      the 1187 AIDS cases, the percentage of women rose from 8% to 25%. The route of
      HIV infection which has most varied over time has been that of heterosexual
      relations (68%). Despite being the most frequent form of AIDS presentation,
      opportunistic infection has decreased from 79% to 51%. Tuberculosis, pneumonia by
      Pneumocystis carinii and cerebral toxoplasmosis as forms of presentation have
      also decreased on performing routine primary prophylaxis for these opportunistic
      infections. A significant trend towards improvement in survival over time was
      observed, mainly due to better prognosis of patients in whom AIDS diagnosis was
      obtained due to pneumonia by P. carinii or Kaposi's sarcoma. CONCLUSIONS: There
      has been an increase in the percentage of women and heterosexual transmission in
      AIDS, as well as an important change in the form of AIDS presentation probably
      due to the systematic administration of primary prophylaxis for several
      opportunistic infections. There has also been a global improvement in survival.

PMID- 8744370
TI  - [Detection of anti-Treponema pallidum antibodies with colloidal gold
      immunoprobes].
AB  - BACKGROUND: The aim of this study was to evaluate the usefulness of colloidal
      gold probes widely used in histochemistry and electronic microscopy for the
      serologic diagnosis of syphilis. METHODS: One hundred eighty-nine sera which had
      been submitted to the traditional fluorescent trigenemic absorption (FTA-ABS)
      test and had later been tested with the new colloidal gold probe method (IAT
      ABS). RESULTS: Out of a total of 103 positive samples by FTA-ABS all were
      positive when tested by gold immunoprobes (sensitivity 100%). Eighty-six samples
      which were negative by immunofluorescence were all negative by IAT-ABS
      (specificity 100%). CONCLUSIONS: The new method of colloidal gold probes with the
      current microscopy is useful for confirming serologic diagnosis of syphilis.

PMID- 8744369
TI  - [Invasive Streptococcus agalactiae infections at a general university hospital
      over a 10-year period].
AB  - BACKGROUND: Streptococcus agalactiae is a known causal agent of neonatal
      meningitis, sepsis and puerperal infections. The incidence of invasive infections
      caused by Streptococcus agalactiae has increased in recent years in non gestating
      adults: in the elderly, patients receiving prolonged steroid treatment or those
      with chronic immunosuppressive diseases. The clinical and epidemiological
      characteristics and risk factors associated to invasive infections caused by S.
      agalactiae were analyzed. METHOD: A retrospective study was undertaken in
      patients with invasive disease by S. agalactiae attended in the Hospital
      Universitari Germans Trias i Pujol in Badalona (Barcelona), Spain, from 1983 to
      1993. RESULTS: S. agalactiae was isolated in 51 patients including 13 (25%)
      neonates. Three patients presented invasive puerperal infection. Thirty-five
      adult patients with a mean age of 62 years presented invasive disease. Infection
      involved bacteremia in 26 (74.2%) patients. S. agalactiae was isolated in the
      ascitic fluid of 4 patients with liver cirrhosis with spontaneous bacterial
      peritonitis (one with bacteriemia) and in the peritoneal exudate of two patients
      with peritonitis secondary to intestinal perforation. Of 5 patients with septic
      arthritis, 3 involved bacteremia. Two patients presented empyema by S.
      agalactiae. Mortality was 28%, being directly related with infection in 4 cases
      (7.8%). CONCLUSIONS: Without taking pregnant women into account, 68% of the cases
      of invasive infections by S. agalactiae were observed in adults with associated
      base disease, with liver cirrhosis, neoplasms and diabetes mellitus being the
      most frequent. Advanced age was also found to be an important predisposing
      factor.

PMID- 8744373
TI  - [Pneumonia diagnosed with bronchoscopy in HIV-positive patients].
AB  - BACKGROUND: The object of our research is to analyse the microbiological results
      of the samples which have been obtained by means of fibronchoscopy (FB) from HIV
      positive patients from 1991 until 1993. METHODS: Sixty fibrobronchoscopies were
      carried out on fifty-seven HIV positive patients. In every case, samples of
      bronchoaspirate (BAS), bronchoalveolar lavage (BAL) and telescoping plugged
      catheter (TPC) were cultured; the last two in a quantitative way. Pneumocystis
      carinii was investigated in BAL by means of immunofluorescence with monoclonal
      antibodies. RESULTS: Some microorganisms were isolated in forty-seven
      bronchoscopies. Thirteen episodes resulted negative. The most frequent etiologic
      agent was Pneumocystis carinii (seventeen cases). The etiology of fifteen
      episodes was polymicrobial. The intersticial radiological pattern was the
      predominant one. It was observed in twenty-seven cases. With regard to immunity,
      91% of the patients showed CD4 < 200. CONCLUSIONS: In our research work, the
      samples that have been obtained by means of FB showed a high percentage of
      diagnoses; that is the reason why we regard this technique as very useful for the
      diagnosis of pneumonia in patients with AIDS. Due to the large number of
      bacterian pneumonia, we consider necessary not only the use of BAL, but also that
      of TPC in these processes.

PMID- 8744371
TI  - [Errors of the agar diffusion method to predict Escherichia coli's susceptibility
      to ampicillin-sulbactam and amoxicillin-clavulanic acid].
AB  - BACKGROUND: To evaluate the in vitro activity of the ampicillin-sulbactam and
      amoxicillin-clavulanic acid against Escherichia coli isolations resistant to
      ampicillin and amoxicillin and the efficacy of the disks of ampicillin sulbactam
      10/10 microgram and amoxicillin-clavulanic acid 20/10 micrograms to differentiate
      the susceptible (S) and resistant (R) isolates. METHODS: We evaluated the in
      vitro susceptibility of 100 consecutive clinical isolates of ampicillin and
      amoxicillin resistant E. coli by the broth macrodilution method and disk
      diffusion test against ampicillin-sulbactam and amoxicillin-clavulanic acid.
      RESULTS: For amoxicillin-clavulanic acid the 64% of the isolates were
      susceptible, 34% were moderately susceptible and 2% were resistant. In contrast,
      the in vitro activity of ampicillin-sulbactam was inferior since 13% of the
      isolates were susceptible, 24% moderately susceptible and 63% were resistant. By
      using the disk of ampicillin-sulbactam 10/10 microgram we found a 13% of very
      major errors and a 44% of minor errors when we consider the actual rules of NCCLS
      (R < or = 11 mm and S > or = 15 mm). The best results were achieved when we took
      into account zone size < or = 15 mm as R and > or = 20 mm as S; however, the
      level of errors was high too (25% minor errors). For the disk of amoxicillin
      clavulanic acid 20/10 micrograms we found a 31% of minor errors when using the
      advised break points (R < or = 13 mm and S > or = 18 mm). CONCLUSIONS: We
      consider that the disk diffusion tests are not applicable to these combinations
      when E. coli isolates resistant to aminopenicillin are evaluated. We advise not
      to extrapolate the results of sensibility or resistance from one combination to
      the other because it presents a different in vitro activity.

PMID- 8744372
TI  - [Microbiological study of vulvovaginitis in premenarcheal girls].
AB  - BACKGROUND: A prospective microbiological study of the vaginal swab specimens
      from premenarcheal girls with clinical diagnosis of vulvovaginitis was done from
      the 1st of September 1991 to the 31st of August 1994. PATIENTS AND METHODS:
      Vaginal secretions from premenarcheal girls with clinical findings were examined.
      Most important pathogenic agents were investigated and if there was an
      inflammatory reaction in the Gram stain and a heavy growth on culture, other
      potentially pathogenic agents were considered also. RESULTS: In 70 (28.7%) of the
      262 patients a potentially pathogenic microorganism was found: eight cases (3.0%)
      due to Streptococcus pyogenes, four cases (1.5%) due to Candida albicans. Only in
      one case Neisseria gonorrhoeae was isolated. Among the uncertain etiologic
      agents, Haemophilus influenzae was the most frequently isolated (7.6%). In 25
      (12.6%) of the 198 patients Enterobius vermicularis ova were visualized.
      CONCLUSIONS: Streptococcus pyogenes was the most frequently related organism with
      the vulvovaginitis syndrome among the traditionally established pathogens. The
      role of Haemophilus influenzae should be considered due to the high prevalence of
      isolation in this group of patients. We consider that differential diagnosis with
      Enterobius vermicularis infestation should be done in all cases.

PMID- 8744374
TI  - [Mechanisms of resistance to glycopeptides].

PMID- 8744375
TI  - [Disseminated cervicofacial lesions in a patient with atopic dermatitis].

PMID- 8744376
TI  - [Diarrhea and eosinophilia in a patient with bronchial asthma].

PMID- 8744377
TI  - [Rifabutin].

PMID- 8744378
TI  - [Bacteremia associated with implantable device for central venous access caused
      by Bacillus cereus].

PMID- 8744379
TI  - [Infection caused by pig bite].

PMID- 8744380
TI  - [Subtyping of influenza A virus strains with the fast technic shell-vial (MDCK)].

PMID- 8744381
TI  - [Bacteremia caused by Neisseria subflava and neutrocytic ascites in a female
      patient with hepatic cirrhosis].

PMID- 8744382
TI  - [Leptospirosis in Gran Canaria: report of 2 cases].

PMID- 8744383
TI  - [Respiratory cryptosporidiosis as first manifestation of AIDS].

PMID- 8744384
TI  - [Varicella pneumonia in immunocompetent patient].

PMID- 8744385
TI  - [Neurohormonal factors in heart failure. II].
AB  - Heart failure is a physiopathological condition, with an increasing incidence and
      prevalence, involving the action of a series of mechanisms known as
      "compensators", which are phylogenetically ready to normalize minute volume and
      blood pressure. These mechanisms include the activation of a series of
      neurohormonal systems: the sympathetic nervous system, the aldosterone renin
      angiotensin system, vasopressin arginine, endothelin, which are basically
      vasoconstrictors, with the counterpoint of other vasodilator systems, such as the
      endothelial relaxation factor, certain prostaglandins and the bradykinin
      kallikrein system, which modulate global response. The authors review the
      physiopathology of each of these systems, as well as their significance in the
      diagnosis and prognostic evaluation of heart failure. We analyze the possible
      deleterious effects of neurohormonal activation, anatomically and at the
      cardiovascular function level, and try to determine if they are capable of
      explaining the evolution and progression of heart failure, in a truly vicious
      circle, up until the irreversible heart failure phase. We review the current
      importance of the inhibition of the aldosterone renin-angiotensin system in the
      prophylaxis and treatment of heart failure. Furthermore, we describe the present
      day value of the inhibition of the sympathetic nervous system in some forms of
      heart failure. We also analyze the different pharmacological treatments for heart
      failure: diuretics, inotropic agents, vasodilators (in their different
      pharmacological types), paying particular attention to their action on
      neurohormonal systems and their implications in the prognosis and evolution of
      heart failure.

PMID- 8744386
TI  - [Which variables predict the appearance of right bundle-branch block and its
      course after heart transplantation?].
AB  - AIM: The purpose of this study was to analyze a series of variables in donors as
      well as of the preoperative and early and late postoperative of patients
      developing a right branch block of the bundle of His (RBBBH) in the first week
      after heart transplantation (HT), and to evaluate factors predicting the
      disappearance or progression of this conduction disorder. MATERIAL AND METHODS:
      58 consecutive patients having undergone an orthotopic HT were studied. 15 of
      them showed a RBBBH after the HT (age: 43 +/- 13, 12 male, 3 female) and 43 did
      not (age: 54 +/- 17, 40 male and 3 female). ECGs and echocardiographic studies
      were performed after 1 week, 1, 3 and 6 months and 1 year. The following factors
      were analyzed: age and sex of the donor baseline cardiopathy, donor's weight
      related to recipient's weight, time of ischaemia and cardiopulmonary by-pass,
      number of rejections per patient/year, previous pulmonary vascular resistance.
      These parameters were compared among the patients who showed RBBBH and those who
      did not, and between those whose blocks disappeared in the follow-up and those
      whose blocks persisted. RESULTS: We found differences is the sex of donors, age
      of recipients, baseline etiology and time of cardiopulmonary by-pass (with block:
      43 +/- 13 years old, dilated cardiomyopathy 73%, 106 +/- 25 minutes, whereas
      without block: 54 +/- 17 years old, dilated cardiomyopathy 42%, 92 +/- 18). The
      different parameters between the patients whose block underwent a regression or a
      progression were sex, lung resistances and right ventricle diameter (progression
      of the block: men 100%, 3.43% +/- 1.05 UW, progressively growing ventricular
      diameters. No progression or regression of the block: men 67%, 1.63 +/- 0.74 UW,
      ventricular diameters with progressive decrease). CONCLUSION: Younger recipients,
      with a diagnosis of dilated cardiomyopathy, to whom a woman's heart is implanted
      and who show a longer extracorporal circulation time are those who show a higher
      incidence of RBBBH: Male patients with high pulmonary resistances undergo a
      progressive increase in the diameter of the right ventricle and a progressive
      increase in the RBBBH degree.

PMID- 8744387
TI  - [Tutorial training in cardiology and cardiothoracic surgery. Preliminary report].
AB  - INTRODUCTION AND OBJECTIVES: Personal contact has been lost in medical training
      due to the increase in numbers of medical students but not of teachers. This fact
      has impaired training in medical specialties. This is the reason that the
      Hospital for Cardiology has developed a program of tutelary training. In this
      paper we present our initial evaluation of this program. METHODS: The inclusive
      criteria for tutors and students have been defined as have the procedures to
      develop the program. After three months, 20 residents involved in the tutelary
      training program were randomly analyzed. Academic activities, clinical practice,
      research activities and extra-academic activities were evaluated. RESULTS:
      Currently there are 14 tutors. 50% of residents have developed research projects,
      60% has increased academic activities, 50% has improved clinical practice and 65%
      has defined their postgraduate research projects. CONCLUSIONS: It was concluded
      that tutelary training in Cardiology and Cardiothoracic Surgery is a useful
      alternative to improve quality of graduates in these specialties.

PMID- 8744388
TI  - [Detection of residual ischemia after acute anterior myocardial infarction using
      Thallium-201 SPECT].
AB  - OBJECTIVES: To assess the utility of single photon emission computed tomography
      (SPECT) with Thallium-201 after anterior myocardial infarction at predischarge
      time in the detection of; a) the prevalence of isotopic redistribution in the
      infarct area or at a distance; b) the correlation between peri-infarction
      ischemia and the angiographic state of the infarct-related artery, and c) the
      correlation between ischemia at a distance and the presence of multivessel
      disease. MATERIAL AND METHOD: Seventy-three survivors of an uncomplicated
      anterior myocardial infarction, 67 men and 7 women, with a mean age of 56 +/- 9
      years (34-70 range), underwent T1-SPECT after stress test (62 exercise test and
      11 pharmacological Dipyridamole test) as well as coronarographic studies before
      discharge. Peri-infarction ischemia was defined as redistribution presence in the
      distribution territory of the left anterior descending artery (LAD) and was
      assessed in a semi-quantitative way scoring both stress and rest images that
      allowed the calculation of a redistribution index R (Stress Score-Rest
      Score/Stress Score). Ischemia at a distance was defined as redistribution
      presence in the territories of circumflex and right coronary arteries as assessed
      both by visual analysis (VA) and bull's eye polar maps (BE) or by washout imaging
      (WO). RESULTS: Peri-infarction ischemia (R > 0) was found in 48 (65.7%) patients;
      43 with and 5 without significant residual lesions in the LAD and the absence of
      peri-infarction ischemia (R = 0) was found in 25 (34.3%) patients, 19 with and 6
      without significant residual lesions in the LAD. Sensitivity and specificity for
      multivessel disease detection by ischemia at a distance was 64% and 85%
      respectively, for VA; 60% and 77% for BE; and 95% and 65% for WO. Combinations of
      different analytical methods (multiparametric approach) showed a decrease in
      sensitivity but improved specificity and positive predictive value: 60%, 90% and
      75%, respectively, for BE & WO; 44%, 90% and 69% for VA & BE and 60%, 92% and 79%
      for VA & WO. CONCLUSIONS: TI-SPECT imaging is a useful diagnostic method to
      detect both peri-infarction ischemia and ischemia at a distance at predischarge
      time following anterior myocardial infarction. Redistribution presence in the non
      infarct-area shows a fair sensitivity and a high positive predictive value to
      detect residual multivessel disease.

PMID- 8744389
TI  - [Evaluation of pulmonary arteries using nuclear magnetic resonance in patients
      with pulmonary atresia].
AB  - OBJECTIVES: Patients with pulmonary atresia and a ventricular septal defect have
      one outlet vessel; the aorta. The pulmonary arteries may be present or absent,
      and there is a collateral shunt. Magnetic resonance imaging is used to study
      this. MATERIAL AND METHODS: We evaluated 10 patients with pulmonary atresia with
      ventricular septal defect. Five were males and the others were females, ages
      ranged between 1 day and 25 years, three patients were newborns. We used common
      planes, but mainly: axial-transverse and coronal, normal and right or left
      oblique projections. RESULTS: The size of the ventricular septal defect was 1.75
      +/- 0.67 cm (0.5-3.2). The pulmonary trunk was absent in 7 patients, it was
      atretic in 2 and it was present in one. Confluent pulmonary branches were seen in
      6 patients (right 0.58 +/- 0.12, left 0.53 +/- 0.19), not confluent in 2 (with
      only one branch in each case) and absent in the other two. There was collateral
      shunt flowing from the descending aorta in 7 patients, from the ascending aorta
      in two and from the aortic in the final case. The ascending aorta was dilated in
      all cases (diameter 3.04 +/- 1.39), afterwards the relation between the ascending
      aorta and the descending aorta was 1.87 +/- 0.25. The aortic arch was right sided
      in 5 patients. CONCLUSIONS: Magnetic resonance imaging is an alternative
      diagnostic method to angiocardiography. It gives complete information about the
      size, the position and the connection of the pulmonary arteries. It is also
      useful to evaluate the aortopulmonary to bronchial shunt.

PMID- 8744390
TI  - [Cardiomyoplasty as treatment of chronic severe cardiac failure].
AB  - INTRODUCTION AND OBJECTIVES: Cardiac assistance from skeletal muscle is now
      emerging as an alternative to transplant surgery. The principle of
      cardiomyoplasty is chronic electrostimulation of the latissimus muscle flap
      wrapped around the heart to obtain a phasic activity which can be integrated to
      ventricular kinetics. Cardiomyoplasty is appropriate for patients with cardiac
      insufficiency refractory to optimal medical treatment. This includes cardiac
      failure of ischemic and non-obstructive cardiomyopathies. Worldwide clinical
      experience with this technique involves more than 500 cases. MATERIAL AND
      METHODS: The Broussais Hospital clinical experience involves 80 patients,
      operated between 1985 and 1995. All of them were closely followed in the
      postoperative period. RESULTS: Recent basic and clinical data have shown that
      cardiomyoplasty effects on ventricular performance are due to: 1) augmentation of
      pump function: 2) limitation of cardiac dilatation; 3) reduction of ventricular
      wall stress, and 4) reverse remodeling of the left ventricular geometry.
      Remarkably, continuous fatigue free contraction of the latissimus dorsi muscle at
      the frequency of the heart has been obtained for periods exceeding 10 years in
      humans. Five patients underwent cardiac transplantation due to refractory heart
      failure. CONCLUSIONS: Clinical experience has demonstrated that cardiomyoplasty
      is an efficient technique to assist patients with severe refractory cardiac
      failure. In the great majority of cases it reverses the heart failure and
      increases life expectancy. Moreover, the functional class and the quality-of-life
      are significantly improved. Cardiomyoplasty does not preclude the use of future
      orthotopic heart transplantation.

PMID- 8744391
TI  - [Effects of nitroglycerin and nifedipine on stunned myocardium due to brief
      repeated ischemias].
AB  - OBJECTIVE: To analyze whether nitroglycerin and nifedipine can reduce myocardial
      stunning due to very brief, repeated coronary ischemias. MATERIAL AND METHODS: In
      33 anaesthetized and open chest dogs, the lengthening and shortening fractions
      were analyzed with ultrasonic crystals in the ischemic and control myocardial
      areas. Twenty repeated coronary occlusions of 2 minutes each, with a recovery
      time of 3 minutes between each occlusion, were induced. At the beginning of the
      experiment, nitroglycerin (0.3 mg i.v. and 80 micrograms/kg/min perfusion) was
      administered in series A (n = 8), nifedipine (5 mu/kg i.v. and 1 microgram/kg/min
      perfusion) in series B (n = 9). The results were compared with control results (n
      = 16) without drugs. RESULTS: Changes in the shortening fraction of the ischemic
      area during coronary occlusions were similar in all three series; after the last
      occlusion the shortening fraction in the control series was -14.9% with respect
      to basal values, -14.6% in series A and -16.6% in series B. Sixty minutes after
      the last ischemia, the shortening fraction impairment in respect to the basal
      values was larger in the control series (-18.9%) and in series A (-16.9%). In
      series B there was recovery (-13.5%) (p < 0.05 vs control series). CONCLUSIONS:
      Our study indicates that nitroglycerin does not seem to have cardioprotective
      effects against brief, repeated ischemia. However, nifedipine decreases
      postischemic dysfunction due to this model of ischemia, probably by avoiding the
      intracellular Ca overload produced during cardiac ischemia.

PMID- 8744392
TI  - [Myocardiopathies. IX. Surgical treatment of hypertrophic obstructive
      myocardiopathy: is it an underestimated alternative?].
AB  - The aim of surgery in hypertrophic cardiomyopathy is to reduce the
      intraventricular obstacle, increase left ventricular compliance, correct mitral
      regurgitation and other associated lesions, such as coronary atherosclerosis
      disease or endocarditis. Several surgical techniques have been proposed; myotomy,
      myomectomy, mitral valve replacement and mitral valve plication. The last
      mentioned technique combined with myomectomy can be performed safely and may
      represent an alternative to mitral valve replacement in cases with enlarged and
      elongated mitral leaflets. We review the natural evolution of the disease and its
      treatment, emphasizing on the possible mechanism by which surgical treatment may
      ameliorate the disease.

PMID- 8744393
TI  - [Aneurysm of the left main coronary artery caused by thoracic trauma].
AB  - A 30 years-old female patient, presented with a clinical picture of acute
      pulmonary edema associated with anterior myocardial necrosis following a car
      accident with mild blunt chest injury. The coronary angiogram showed the
      existence of an aneurysm in the left main coronary artery (LMCA) causing
      extrinsic compression of the artery. Subsequent angiograms showed a complete
      disappearance of the aneurysm. The patient remains symptom-free three years after
      the accident. Blunt chest injury is a potential cause of heart damage. Although
      the coronary arteries may be damaged, the development of an aneurysm has been
      reported on very few occasions and always in connection with the anterior
      descending coronary artery. Our case is the first case described with the
      location of the aneurysm in the left main artery.

PMID- 8744394
TI  - [Acute hepatitis caused by intravenous amiodarone].
AB  - Amiodarone is an antiarrhythmic agent very often used in clinical practice in
      spite of its large array of adverse effects. We report one patient case with
      acute hepatitis following intravenous amiodarone treatment and its possible
      etiology. Our conclusion is the importance of a strict control of parameters in
      the hepatic functions in patients who require amiodarone therapy.

PMID- 8744396
TI  - [Effect of pharmacological interventions on progression of coronary
      atherosclerosis].

PMID- 8744395
TI  - [Infectious endocarditis caused by Q fever].
AB  - A case of aortic valve endocarditis caused by Coxiella burnetii and operated on
      with success is reported. The patient is doing well at 18 months follow up.
      Diagnosis of Q-fever endocarditis was made by high antibodies against phase I
      Coxiella burnetii antigens titration and by demonstration of aortic valvular
      vegetations by bidimensional echocardiography. Our patient suffered emergency
      aortic valve substitution due to acute hemodynamic failure and started a long
      term treatment with doxycycline and rifampicin. Some interesting aspects about
      the diagnosis and treatment of this patient are reviewed because long-term follow
      up and serological controls are still rare in the literature.

PMID- 8744397
TI  - APP transgenesis: approaches toward the development of animal models for
      Alzheimer disease neuropathology.

PMID- 8744398
TI  - Rational design of an animal model for Alzheimer's disease: introduction of
      multiple human genomic transgenes to reproduce AD pathology in a rodent.
AB  - A major obstacle to understanding the pathogenesis of Alzheimer's disease is the
      lack of easily studied animal models. Our approach is to apply transgenic methods
      to humanize mice and rats, employing methods that introduce large genomic
      transgenes, because this improves the level of transgene protein expression and
      the tissue specificity of expression. Our plan is to reproduce AD pathology in
      rodents by making them transgenic for several human proteins involved in AD. This
      report describes transgenic animal lines that we have produced, and summarizes
      our current approach and future plans. Two human genes known to be involved in AD
      pathology are the amyloid precursor protein (APP) and the E4 isoform of
      apolipoprotein E (apoE4). So far, we have produced and analyzed a transgenic line
      carrying the entire human APP gene cloned in a yeast artificial chromosome. We
      have also produced but not yet analyzed a mouse carrying the human apoE4 gene.
      Work is in progress to produce a transgenic line carrying a disease-causing
      mutation in the human APP gene. As we produce these animals, we are breeding them
      together, and also breeding them with a mouse line that lacks endogenous apoE, to
      produce an animal model carrying several human proteins whose interaction is
      believed to be instrumental in development of AD pathology. These transgenic
      animals will be useful for dissecting the biochemical and physiological steps
      leading to AD, and for development of therapies for disease intervention.

PMID- 8744399
TI  - Expression of APP in transgenic mice: a comparison of neuron-specific promoters.
AB  - The beta-amyloid precursor protein (APP) carries mutations in codons 717 or
      670/671, which cosegregate with familial forms of Alzheimer's disease (AD). As an
      initial step to study the related pathogenetic mechanisms in vivo we have
      generated transgenic mice expressing APP with these mutations. Several neuron
      specific promoters were used to drive expression of human APP cDNAs. Only the Thy
      1 promoter yielded transgene expression levels comparable to or above the
      endogenous mouse levels. Deletion of a 121 bp sequence from the 3' untranslated
      region of APP appeared to increase mRNA levels. Transgene mRNA was found
      throughout the brain with highest levels in hippocampus and cerebral cortex.
      Accordingly, human APP was detected in these regions by Western blotting. Protein
      levels paralleled mRNA levels reaching or exceeding the amount of endogenous APP.
      Variable reactivity of human APP in cell bodies was shown by immunocytochemistry.
      Although our initial histological examinations did not reveal any alterations
      characteristic of AD, further studied will be required.

PMID- 8744400
TI  - Transgenic mice expressing APP-C100 in the brain.
AB  - The classic hallmarks of Alzheimer's disease are the deposition of amyloid in
      plaques and in the cerebrovasculature, and the emergence of neurofibrillary
      tangles in neurons. The interplay between these two pathologic processes, on the
      one hand, and the degeneration of neurons and loss of cognitive functions on the
      other, remains incompletely understood. We have proposed that one crucial
      component of this interplay is a fragment of the Alzheimer amyloid protein
      precursor (APP) comprising the carboxyterminal 100 amino acids of this molecule,
      which we term APP-C100 (or, more simply, C100). This fragment, which comprises
      the 42-amino acid amyloid protein (A beta) and an additional 58 amino acids
      carboxyterminal to it, was found to be toxic specifically to nerve cells in
      vitro. We developed transgenic mouse models to test the hypothesis that APP-C100
      causes Alzheimer's disease neuropathology. APP-C100 was delivered to the mouse
      brain via a transgene expressing C100 under the control of the dystrophin brain
      promoter. These transgenic animal models for the action of APP-C100 in the brain
      exhibited some of the neuropathological features characteristic of Alzheimer
      disease brain. The animal models that we have created can be used to test
      hypotheses concerning the mechanism by which C100 interacts with a neuronal
      receptor to kill neurons.

PMID- 8744401
TI  - Lack of beta-amyloidosis in transgenic mice expressing low levels of familial
      Alzheimer's disease missense mutations.
AB  - Point mutations within the beta-amyloid precusor protein (beta-APP) gene known to
      segregate with Alzheimer's disease in certain families were introduced into human
      beta-APP cDNAs and expressed under the control of a neuron-specific enolase (NSE)
      promoter in mice. The transgenic animals exhibited transgene expression
      predominantly in neocortex and hippocampus where the levels were maximally 1.3
      fold of those of wild-type mouse beta-APP. Quantitative immunoblot analysis in
      homozygous mice carrying different missense mutations showed slightly increased
      alpha-secretory processing. In V7171 mice compared to nontransgenic mice there
      was more alpha-secretory beta-APP (beta-APPsec) in cortex/hippocampus, less in
      cerebellum, and no difference in midbrain/brain stem. In none of the transgenic
      animals tested was a 4 kDa amyloid fragment detected by Western blotting of brain
      extracts, immunohistochemistry, or by 125I-A beta-binding onto brain sections. No
      glial reaction was observed. Behavioral analysis of mice carrying the V7171
      mutation showed no appreciable deficit in comparison to wild-type mice. Together,
      these data suggest that low levels of expression of mutated beta-APP in 10-12
      month-old transgenic mouse brains result in slightly more beta-APPsec, and are
      insufficient to induce amyloidogenic processing and AD-like pathology.

PMID- 8744402
TI  - Accumulation of beta-amyloid fibrils in pancreas of transgenic mice.
AB  - Some forms of familial Alzheimer's disease are caused by mutations in the amyloid
      beta protein precursor (beta APP), and there is excellent evidence that these
      mutations foster amyloid deposition by increasing secretion of total amyloid beta
      protein (A beta) or the highly amyloidogenic A beta 1-42 form. These observations
      provide a powerful rationale for developing an animal model of AD by generating
      transgenic mice in which cerebral amyloid deposition is induced by A beta
      overproduction. To produce substantial A beta in vivo, we generated mice
      expressing the transgene of signal peptide and 99 residues of carboxyl-terminal
      fragment (CTF) of beta APP under control of the cytomegalovirus enhancer/chicken
      beta-actin promoter. The transgenic mRNA was detected in many tissues of these
      mice, but the levels of transgenic mRNA, CTF, and A beta did not correlate well
      indicating that tissue-specific posttranslational processing may play an
      important role in determining the amount of A beta that accumulates in various
      tissues. A beta was detected biochemically in brain, kidney, and pancreas with
      the largest amount present in pancreas. In transgenic plasma, there was a marked
      accumulation of human A beta 1-40 and A beta 1-42(43) to levels over 30-times
      those observed in normal human plasma. Thus, the transgenic mice produce and
      secrete considerable A beta. Despite this increase in A beta secretion and the
      elevated A beta in brain, immunohistochemistry revealed no consistent cerebral A
      beta deposition. In pancreas, however, intracellular A beta deposits were
      detected immunohistochemically in acinar cells and interstitial macrophages, some
      of which showed severe degeneration. In addition, examination of these cells by
      immunoelectron microscopy revealed many putative amyloid fibrils (7-12 nm) that
      were stained by anti-A beta antibodies. Overall, our findings indicate that
      tissue-specific posttranslational processing may play a pivotal role in A beta
      production and amyloid fibril formation in vivo. By carefully analyzing the
      changes that occur in the transgenic mice described here as compared to the
      transgenic line that has recently been shown to form extracellular amyloid
      plaques in brain, it may be possible to gain considerable insight into the
      factors that determine the location and amount of A beta that accumulates as
      amyloid.

PMID- 8744403
TI  - Artifactual strain-specific signs of incipient brain amyloidosis in APP
      transgenic mice.
AB  - In an attempt to generate transgenic mice modeling Alzheimer-type
      amyloidogenesis, the COOH-terminal 103 residue human APP segment was expressed in
      brain regions known to be vulnerable in AD. Transfected cells overexpressing this
      transgene were previously shown to develop intracytoplasmic inclusions that were
      immunoreactive with antibodies to the APP COOH-terminus. Transgenic C57B6/SJL
      mice produced transgene-coded mRNA in their brains at levels up to sixfold above
      endogenous APP, most abundantly within cortical and hippocampal pyramidal
      neurons. Immunocytochemistry with anti-A beta antibodies revealed occasional
      structures that resembled diffuse amyloid, but which could not be detected on
      serial sections. Immunolabeling with antibodies to APP regions NH2-terminal to
      the transgene-coded domain revealed elevated immunoreactivity within perikarya
      and neurites in regions expressing the highest transgene and endogenous APP mRNA
      levels, similar to observations previously reported within vulnerable neurons in
      AD brain. However, subsequent breeding revealed that this phenotype segregated
      with the B6/SJL background rather than the transgene, thus emphasizing the
      importance of genetic background to observations of putative AD-type pathology in
      transgenic animals.

PMID- 8744405
TI  - A beta-associated cerebral angiopathy and senile plaques with neurofibrillary
      tangles and cerebral hemorrhage in an aged wolverine (Gulo gulo).
AB  - In this study of an aged wolverine (Gulo gulo), we document neuropathologic
      lesions (cerebral amyloid angiopathy (CAA), neuritic plaques (NPs),
      neurofibrillary tangles (NFTs), and granulovacuolar degeneration strikingly
      similar to those present in aging and Alzheimer's disease (AD), with the
      additional finding of concurrent cerebral hemorrhage. A beta immunoreactive
      cerebral amyloid angiopathy and senile plaques (neuritic and diffuse) were
      present throughout the cerebral cortex and hippocampus. Ubiquitin
      immunoreactivity was noted in peripheral portions of some of the plaques.
      Argyrophilic intracellular neurofibrillary tangles containing abnormally
      phosphorylated (Ser 202) tau protein were present within cortical and hippocampal
      neurons. The wolverine should be added to the list of nonhuman species (dogs,
      nonhuman primates, polar bears) with amyloid deposits similar to those in aged
      humans and in humans with AD. The aged wolverine appears to be distinct from
      other nonhuman species in possessing plaques and NFTs, as well as other
      histologic cerebral lesions frequently associated with AD.

PMID- 8744404
TI  - Neurodegenerative changes including altered tau phosphorylation and neurofilament
      immunoreactivity in mice transgenic for the serine/threonine kinase Mos.
AB  - Transgenic mice expressing the oncogenic protein-serine/threonine kinase Mos at
      high levels in the brain display progressive neuronal degeneration and gliosis.
      Gliosis developed in parallel with the onset of postnatal transgene expression
      and led to a dramatic increase in the number of astrocytes positive for GFAP,
      vimentin, and possibly tau. Interestingly, vimentin is normally expressed only in
      immature or neoplastic astrocytes, but appears to be induced to high levels in
      Mos-transgenic, mature astrocytes. Mos can activate mitogen activated protein
      kinase (MAPK) and MAPK has been implicated in Alzheimer-type tau phosphorylation.
      In the Mos-transgenic brain we found increased levels of phosphorylation at one
      epitope on tau containing serines 199 and 202 (numbering according to human tau),
      a pattern similar but not identical to that found in Alzheimer's disease. In
      addition, Mos-transgenic mice express a novel neurofilament-related protein that
      might be a proteolytic neurofilament heavy chain degradation product. These
      results suggest that activation of protein phosphorylation in neurons can result
      in changes in cytoskeletal proteins that might contribute to neuronal
      degeneration.

PMID- 8744406
TI  - Carboxy terminal of beta-amyloid deposits in aged human, canine, and polar bear
      brains.
AB  - Immunocytochemistry, using antibodies specific for different carboxy termini of
      beta-amyloid. A beta 40 and A beta 42(43), was used to compare beta-amyloid
      deposits in aged animal models to nondemented and demented Alzheimer's disease
      human cases. Aged beagle dogs exhibit diffuse plaques in the absence of
      neurofibrillary pathology and the aged polar bear brains contain diffuse plaques
      and PHF-1-positive neurofibrillary tangles. The brains of nondemented human
      subjects displayed abundant diffuse plaques, whereas the AD cases had both
      diffuse and mature (cored) neuritic plaques. Diffuse plaques were positively
      immunostained with an antibody against A beta 42(43) in all examined species,
      whereas A beta 40 immunopositive mature plaques were observed only in the human
      brain. Anti-A beta 40 strongly immunolabeled cerebrovascular beta-amyloid
      deposits in each of the species examined, although some deposits in the polar
      bear brain were preferentially labeled with anti-A beta 42(43). beta-amyloid
      deposition was evident in the outer molecular layer of the dentate gyrus in the
      aged dog, polar bear, and human. Within this layer, A beta 42 was present as
      diffuse deposits, although these deposits were morphologically distinct in each
      of the examined animal models. In dogs, A beta 42 was cloud-like in nature; the
      polar bear demonstrated a more aggregated type of deposition, and the nondemented
      human displayed well-defined deposits. Alzheimer's disease cases were most
      frequently marked by neuritic plaques in this region. Taken together, the data
      indicate that beta-amyloid deposition in aged mammals is similar to the earliest
      stages observed in human brain. In each species, A beta 42(43) is the initially
      deposited isoform in diffuse plaques.

PMID- 8744407
TI  - The canine as an animal model of human aging and dementia.
AB  - The aged canine displays many features that make it an excellent model for
      studying the progression of pathology in brain aging and linking these findings
      to learning, memory and other cognitive functions. Canines develop extensive beta
      amyloid deposition within neurons and their synaptic fields, which appears to
      give rise to senile plaques. These plaques are primarily of the early diffuse
      subtype. Aged canines also exhibit accumulations of lipofuscin, cerebral vascular
      changes, dilation of the ventricles, and cytoskeletal changes. Neurofibrillary
      tangles (NFTs) are not present in the aged canine. Thus, the aged canine brain
      provides a suitable model for studying early degeneration normally considered to
      be pre-Alzheimer's. This supposition is also supported by behavioral data. We
      have found that the extent of beta-amyloid deposition correlates with a decline
      in select measures of cognitive function. These data provide the first evidence
      of a correlation between beta-amyloid accumulation and cognitive decline in the
      absence of NFTs. We summarize four lines of evidence that support using the aged
      canine as a model of human aging: (a) Aged canines develop aspects of
      neuropathology similar to that observed in aged humans; (b) Veterinarians have
      observed that many canines exhibit a clinical syndrome of age-related cognitive
      dysfunction; (c) Aged canines are deficient on a variety of neuropsychological
      tests of cognitive function; (d) The level of beta-amyloid accumulation
      correlates with cognitive dysfunction in the canine. These data indicate that the
      aged canine is a particularly useful model for studying age-related cognitive
      dysfunction (ARCD), early neuronal changes associated with aging, and the initial
      stages of senile plaque formation.

PMID- 8744408
TI  - Age-specific onset of beta-amyloid in beagle brains.
AB  - As part of an effort to characterize Alzheimer's disease-like neuropathy in the
      canine brain we have determined the age of onset of spontaneous beta-amyloid
      deposition in 103 laboratory-raised beagles. Tissue samples for each subject were
      obtained from hippocampal and cortical regions and examined for the incidence and
      density of beta-amyloid deposition after staining with modified Bielschowsky
      silver stain and immunohistochemistry. Amyloid deposition was characterized as
      diffuse plaque or cloud-like formation. The diffuse type of beta-amyloid plaque
      formation predominated in all brain regions examined. A threshold effect of
      plaque development was observed; no plaques were apparent in dogs before the age
      of 10 years, while 36% of dogs aged 11.1-12.9, 60% of dogs aged 13.0-15.0, and
      73% of dogs aged 15.1-17.8 developed beta-amyloid deposits. Additionally, a
      significant increase in plaque density was observed with increasing age.

PMID- 8744409
TI  - Cerebral amyloid angiopathy and plaques, and visceral amyloidosis in aged
      macaques.
AB  - In the present study, we report our extended data on the incidence of two types
      of cerebral amyloidosis (plaques and plaques associated with angiopathy) and
      visceral amyloidosis in late adult and aged captive rhesus monkeys (Macaca
      mulatta). In a total of 81 brains from animals ranging from 16 to 39 years old,
      beta-amyloid plaques were found in 38, 10 of which were associated with amyloid
      angiopathy. Brains from eight adults, 16 to 19 years, had no lesions. In aged
      groups, the rates were 20.8% in the 20- to 25-year group (24), 60.9% in the 26-
      to 31-year group (41), and 100% in the 33- to 39-year group (8). Twelve monkeys
      in these aged groups had an involvement of amyloidosis in either the liver, the
      adrenal, or the pancreatic islets, and 7 of 12 had amyloid plaques (5) and
      plaques associated with cerebral angiopathy (2). No neurofibrillary tangles were
      detected in these brain lesions. Amyloid in both plaques and cerebral angiopathy
      showed immunocytochemical crossreactivity with human amyloid beta (beta/A4) and
      precursor proteins (APP-A4), but visceral amyloid was negative.
      Ultrastructurally, amyloid initially appears as loose filaments in the
      perivascular or Disse space, and they further aggregate to produce dense
      interlacing bundles. Cerebral amyloid angiopathy associated with plaque appears
      to be a subclass of senile plaque lesions in aged monkeys as well as in aged
      humans, and it appears to have no pathogenetic correlation with visceral
      amyloidosis.

PMID- 8744410
TI  - The older rabbit as an animal model: implications for Alzheimer's disease.
AB  - Eyeblink classical conditioning (EBCC) is impared in rabbits and humans during
      normal aging and severely disrupted in Alzheimer's disease (AD) and older Down's
      Syndrome patients (called DS/AD). To determine if older rabbit brains developed
      neuropathological evidence of Alzheimer-like pathology to account for impaired
      EBCC, the cerebellum and hippocampus of behaviorally tested rabbits aged 3 months
      to 7 years were probed using immunohistochemical techniques. Significant cell
      loss and gliosis were observed in some brain regions, but there was little or no
      deposition of beta-amyloid (A beta) or abnormal tau accumulations in
      telencephalic neurons, even in rabbits over 7 years of age. Our aims here are to:
      1) report the results of our search for Alzheimer-like neuropathology in aged
      rabbit brains; and 2) highlight similarities in the brain mechanisms for EBCC
      between rabbits and humans and, hence, the utility of studies of EBCC in rabbits
      as a model system for testing cognition-enhancing drugs.

PMID- 8744411
TI  - Intraneuronal beta-amyloid immunoreactivity in the CNS.
AB  - The high degree of overlap in the neuropathologic outcome of Alzheimer's disease
      (AD), Down's Syndrome (DS), and coronary heart disease suggest a possible
      interrelationship. The pattern of hippocampal and cortical intraneuronal beta A4
      immunoreactivity is strikingly similar in AD, DS, coronary heart disease, and two
      separate animal models of coronary heart disease. Cells in fascia dentata and
      large cortical neurons were beta A4 immunodecorated in half the AD and DS
      subjects studied. Similar neuronal staining occurred in half the age-matched
      coronary heart disease subjects, but was absent in each nonheart disease control
      investigated. Analogous accumulations of neuronal beta A4 immunoreactivity were
      induced in rabbit brain by dietary administration of high cholesterol, and this
      effect could be reversed by regression of the experimental diet. Decreased
      density (p < 0.05) and cellular staining intensity occurred after 2 weeks of
      control diet following 8 weeks of high cholesterol. Microgliosis accompanied the
      accumulation of beta A4 immunoreactivity in the cholesterol-fed rabbits and
      persisted after regression of the diet and decreases in neuronal beta A4
      immunoreactivity. An identical pattern of neuronal beta A4 immunoreactivity was
      induced in the brains of adolescent pigs after acute ligation of the left
      anterior descending coronary artery (LAD) compared to surgical and anesthetic
      controls. The mean number of beta A4 immunoreactive neurons was significantly
      increased (p < 0.05) in the cortex and hippocampus of pigs with a ligated LAD
      compared to both control groups. Increased density and intensity of neuronal beta
      A4 immunoreactivity induced by ligation of the LAD was commensurate with the
      severity of the decreased cardiac output in the LAD group, but not in the
      anesthetic control groups with decreased cardiac output. The incidence of ALZ-50
      (A68) immunoreactive neurons also increased in the ligated pigs compared to both
      control groups. The data suggest a neuronal origin of beta A4 immunoreactive
      peptide(s), which can be cleared from the brain by microglia after severe
      accumulation is induced. This could indicate that reduced clearance of beta-APP
      metabolic by-products could contribute to a metabolic backlog and redirection of
      peptide processing by microglia to extracellular deposition. Neuronal
      accumulation of beta A4 immunoreactivity could be due to the effect of
      circulating factors on brain function in both animals models. It is likely that
      animal models of coronary heart disease may be useful in disclosing the mechanism
      of SP formation and induction of ALZ-50 immunoreactivity irrespective of their
      pathoclinical significance.

PMID- 8744412
TI  - Effects of chronic beta-amyloid treatment on fatty acid incorporation into rat
      brain.
AB  - The present study evaluated the effects of chronic A beta administration on radio
      labeled plasma fatty acid incorporation in rat brain. A beta was chronically
      infused intraventricularly via an osmotic minipump, for 1 week, at a
      concentration of 460 microM. After the infusion, fatty acid incorporation was
      quantified using an in vivo method developed in this laboratory. Three
      radiolabeled fatty acids were separately infused IV in awake animals. Biochemical
      analyses of fatty acid incorporation and histology for A beta showed no
      differences between control (vehicle infusion only) and experimental groups.
      However, in vitro tests on the cytotoxicity of A beta showed that it caused
      significant cell death relative to controls (PC-12 cells). The lack of effect of
      infused A beta on radiolabeled fatty acid incorporation is discussed.

PMID- 8744413
TI  - Rodent models of Alzheimer's disease: rat A beta infusion approaches to amyloid
      deposits.
AB  - The development of rodent models for Alzheimer's disease is a critical step for
      both understanding the disease and developing therapeutic drugs. Transgenic and
      knockout mouse models will elucidate some important aspects of the etiology of
      the disease and the development of pharmaceutical treatments. Here, we will focus
      on the advantages of nontransgenic models. In nontransgenic rat models,
      intraventricular infusion of A beta 1-40 (alone) generally results in diffuse
      deposition of A beta with very few focal plaque-like amyloid deposits after a 30
      day intraventricular infusion. However, we have recently found that large numbers
      of scattered A beta immunoreactive plaque-like deposits can be produced in
      retired female Sprague-Dawley rat breeders using intraventricular infusion of A
      beta combined with neuropil injection of transforming growth factor beta 1(TGF
      beta). A beta that was not associated with the large deposits was often
      immunolocalized with neurons and cell processes. Immunogold electron microscopy
      demonstrated the presence of A beta in endosome/lysosomes of neuronal processes
      and glia and basal lamina. In some cases this labeling was clearly in lysosomes
      of degenerating neurites. This model allows one to introduce A beta and other
      plaque-associated factors without overexpression of potentially confounding APP
      domains. We conclude that A beta infusion models will be a useful complement to
      transgenic approaches to Alzheimer's pathology.

PMID- 8744414
TI  - The expert witness: the whole truth and nothing but...

PMID- 8744415
TI  - Neoadjuvant chemotherapy for locally advanced cervical cancer--where does it
      stand?: a review.
AB  - Platinum-based combination chemotherapy has been utilized in the neoadjuvant
      setting in locally advanced inoperable cervical cancer with the aim of improving
      response and survival. Neoadjuvant chemotherapy can be followed by either
      radiation therapy (RT) or by surgery in cases in which it seems to be
      appropriate. Available data indicate that preradiation chemotherapy yields no
      survival advantage over RT alone. However, presurgery chemotherapy may increase
      resectability in women with locally advanced cervical cancer to around 70
      percent. Nonrandomized trials of neoadjuvant chemotherapy followed by surgery
      have shown some improvement in the outcome. Prospective randomized trials are
      needed to evaluate this approach as compared with RT alone and to define its
      precise role in locally advanced cervical cancer.

PMID- 8744416
TI  - Apoptosis in the human female reproductive tract.
AB  - Throughout fetal and adult life, the balance of cell proliferation and cell death
      determines the size of cell populations in tissues throughout the body.
      Apoptosis, or programmed cell death, is the physiologic process of cell deletion.
      Cell death is critical in morphogenesis in the embryo and fetus as well as in
      maintaining tissue homeostasis in the adult. Throughout the menstrual cycle, cell
      death and renewal occur in the female reproductive tract in a highly regulated
      sequence. The process of follicular atresia and the cyclic shedding of the
      endometrium involve the process of apoptosis. In pathologic states, resistance to
      cell death by apoptosis may play a fundamental role in tumorigenesis. Because
      apoptosis is such a fundamental biologic process in a variety of physiologic and
      pathologic states, many unique to the female reproductive tract, it is imperative
      that clinicians be conversant with the rapidly expanding information in this
      area. Although apoptotic cell death has been recognized histologically for over
      20 years (1), the molecular mechanisms that regulate apoptosis have only recently
      begun to be elucidated. The identification of some of these regulators, such as
      the p53 gene, has improved our understanding of the mechanisms of tumor response
      to chemotherapy. This review will summarize our current knowledge of the
      mechanisms of apoptosis in the ovary and endometrium, and in the normal
      development and malignant transformation of the breast.

PMID- 8744417
TI  - Utility of antibiotic therapy in preterm premature rupture of membranes: a meta
      analysis.
AB  - The optimal management of preterm premature rupture of membranes (PROM) is
      controversial. Maternal risks must be weighed against fetal benefit when
      expectant management is considered. Despite concerns about maternal harm,
      protocols of expectant management seem to afford the best perinatal outcomes.
      Given that infection often is the common pathway for delivery in preterm PROM,
      recent reports have explored the utility of maternal administration of
      antibiotics. In this paper we will summarize these results using meta-analytic
      techniques and assess the impact of antibiotic therapy on maternal and perinatal
      outcomes.

PMID- 8744418
TI  - Phosphatidylinositol phosphate 5-kinase: purification and inhibition studies.
AB  - A membrane-associated phosphatidylinositol phosphate 5-kinase has been purified
      approximately 110,000-fold from sheep brains. The purification procedure
      involves: sodium chloride (1M) extraction of the membrane, 20-40% ammonium
      sulfate fractionation, phosphocellulose (P-11) chromatography, a second
      phosphocellulose chromatography, hydroxyapatite chromatography, heparin Sepharose
      chromatography, HPLC SP(SO3- polymer)-cation exchange chromatography, and HPLC
      gel filtration. The purified enzyme exhibited a final specific activity of 1750
      nmole/min/mg of protein. The molecular mass of the enzyme was estimated to be
      approximately 60 kDa by SDS-PAGE and 130 kDa by HPLC gel filtration. Kinetic
      measurements showed that the apparent Km value of phosphatidylinositol phosphate
      5-kinase for the utilization of ATP is 43 microM. The 2'(3')-0-(2,4,6
      trinitrophenyl) derivative of ATP was found to be an inhibitor of the enzyme. The
      mode of inhibition is competitive, with a Ki value of 55 microM.

PMID- 8744419
TI  - Biochemical characteristics of a human myeloid leukemia cell differentiation
      factor.
AB  - A human lymphocyte-derived maturation-inducing activity, which mediates the
      differentiation of human myeloid leukemia cells HL-60 to monocytic cells, was
      purified and characterized. The maturation inducer is a single polypeptide with a
      molecular mass of 54,300 Daltons. A Pl range of 8.0-8.5 was determined along with
      the amino acid composition of the inducer. In cell cultures, the purified inducer
      mediated a growth reduction and a differentiation of leukemia cells to mature
      monocytes-macrophages, possessing complement receptors and phagocytic capacity.

PMID- 8744420
TI  - Purification and partial characterization of a new anti-A1 lectin of Phaseolus
      coccineus collected in Oaxaca, Mexico.
AB  - It is well known that Phaseolus species contains lectins of various specificities
      1-4. Runner bean5 and different varieties of Ph.coccineus described by Ochoa et
      al6, are not specific to human blood groups. They react indistinctly with
      erythrocytes of the ABO system. However the lectin of Ph. lunatus (lima bean)7 is
      specific to the blood group type A, a classic example of that specificity.
      Sometime ago, we discovered a new lectin in a variety of edible bean of Ph.
      coccineus in the flora of the state of Oaxaca in Mexico, cultivated exclusively
      in the small community of Jamiltepec, near the Pacific coast, which presented
      strong hemagglutinating anti-A1 activity. In this report we describe a
      chromatographic technique for the isolation and purification of this lectin. The
      molecule is a tetramer with a molecular weight of 120 kDa. It requires Ca++ or
      Mg++ for activity, and it is inhibited by N-Acetylgalactosamine (GalNac) at
      concentration of 2.8 mM., NN' N' Triacetylchitotriose, 4-O(4-O-D
      Galactopyranosyl) -D-Galatopyranosyl-D-Glucopyranose, and N' Diacetylchitobiose
      inhibited at moderate concentration (20mM). Conalbumin and ovoalbumin, also
      inhibited hemagglutination.

PMID- 8744421
TI  - Purification of rat liver mevalonate pyrophosphate decarboxylase.
AB  - Mevalonate pyrophosphate decarboxylase was isolated from rat liver to 90% purity
      as judged by SDS-PAGE using Phenyl Sepharose, p-coumaric acid-Sepharose, Mono P,
      and Mono Q chromatography. Gel filtration chromatography of the crude extract
      determined the native enzyme to be near 100 kDa while SDS-PAGE of the purified
      enzyme showed a protein band at 45 kDa. This implies that the native rat liver
      enzyme is a homodimer which differs from the published report that the enzyme is
      a tetramer of 35 kDa subunits. We measured a specific activity of 4.6 units/mg
      and a KM for mevalonate pyrophosphate of 20 microM. These values are similar to
      those reported for the chicken liver and the pig liver enzymes, but differ from
      the published report of the rat liver enzyme.

PMID- 8744422
TI  - Quantification of benzoquinones in the flour beetles. Tribolium castaneum and
      Tribolium confusum.
AB  - Benzoquinones were extracted from flour beetles by rinsing them for 8 min in
      methanol followed by homogenization in fresh methanol. This procedure recovered >
      96% of the total benzoquinones from both species, with the methanolic rinse and
      supernatant representing the "surface" and "total" benzoquinones. As determined
      by UV/VIS spectrometry and reversed-phase HPLC, the methanolic rinse contained
      methyl- and ethyl-1,4-benzoquinone (MBQ and EBQ), but no substituted
      hydroquinones, The methanolic supernatant contained MBQ and EBQ, and methyl- and
      ethyl-hydroquinone. When stored at -20 degrees C for 72 hr, the chemical
      composition of the methanolic rinse did not change, but the composition of the
      methanolic homogenate did change. Notably, the amounts of benzoquinones in the
      methanolic supernatant decreased during storage. The method described represents
      an improvement over those described previously in that it uses less hazardous
      solvents for extraction (methanol vs more non-polar solvents such as hexane) and
      allows for the differentiation and quantification of the surface and total
      benzoquinones of these beetles.

PMID- 8744423
TI  - Small scale biosynthesis and purification of gram quantities of chorismic acid.
AB  - This paper details improvements in the biosynthetic method of purification of
      chorismic acid using Klebsiella pneumoniae 62-1. New growth and accumulation
      conditions yielded 4 L of accumulation medium containing approximately 0.5 g/L of
      chorismate from 2 L of bacterial growth. Improvements in the handling and
      extraction procedures produced yields of approximately 2 g of 75 to 90% chorismic
      acid. A new recrystallization procedure yielded chorismic acid 97% pure by weight
      (using epsilon 275 = 2630 M-1 cm-1), and 99.8% pure by enzymatic conversion.
      These results represent a three- to five-fold increase in yield over average
      published values.

PMID- 8744424
TI  - New rationale in management of tibial agenesis type II: a maturity review of its
      functional, psychological, and economic value.
AB  - It is now 3 years since we published a new surgical approach to type II tibial
      agenesis. All three patients have reached the end of growth, and we have been
      able to conduct a maturity review of the functional, psychological, and economic
      value of this method of treatment. All three patients were very satisfied with
      the treatment they had received, although it was long and often arduous. We have
      attempted to compare the costs of primary amputation without complication in the
      first year of life, followed by supply of at least 10 prostheses, until age 18
      years, with that of the reconstructive technique, which is liable to require five
      operations and considerable periods of inpatients and outpatient care until age
      of 18 years.

PMID- 8744425
TI  - Treatment of congenital pseudarthrosis of tibia with the circular frame
      technique.
AB  - We treated nine patients with congenital pseudarthrosis of the tibia
      consecutively by a modification of the Ilizarov (circular frame) technique. Seven
      patients had had several previous operations, and two patients had had none.
      After resecting of the pseudarthrosis and the surrounding pathologic periosteum,
      we performed acute shortening and compression at the level of resection, together
      with simultaneous lengthening of the proximal tibia. Union was achieved in all
      cases. With this technique, not only the mechanical but also the biologic
      problems are addressed. As compared with other methods, the circular frame
      technique also offers the possibility of correcting angulation and limb length
      discrepancy.

PMID- 8744426
TI  - Management of forme fruste fibular hemimelia.
AB  - Children with fibular hypoplasia and three-or four-ray feet have a forme fruste
      of congenital short tibia with absent or dysplastic fibula. We outline the
      criteria for management of this condition. Although fibular deficiency can be
      considered benign, two thirds of our patients underwent operation. Leg length
      inequality may require epiphysiodesis, leg lengthening, or simply a shoe raise.
      Only very occasionally, when the foot is nonfunctional, is amputation through the
      ankle undertaken.

PMID- 8744427
TI  - Fibular hemimelia: a preliminary report on management of the severe abnormality.
AB  - The introduction of Ilizarov leg lengthening techniques has allowed a change in
      philosophy in treatment of fibular hemimelia. Between January 1990 and October
      1993, eight patients with 10 involved extremities underwent correction of severe
      grades of fibular hemimelia by the Ilizarov technique. Mean follow-up from
      operation was 26.7 months. Because the lengthening desired was achieved in all
      cases, this form of treatment is an attractive alternative to the more
      traditional Syme's amputation. However, complications are common. Frequency and
      severity of complications apparently is less in younger patients who require less
      extensive, staged lengthening.

PMID- 8744428
TI  - Finger fractures in children treated with absorbable pins.
AB  - Biodegradable PDS-rods have been used for the treatment of phalangeal neck
      fractures to oppose the disadvantages and complications of K-wire fixation.
      Reduction can be maintained during fracture healing, and the surrounding joints
      can be mobilized early. Because of the recessed position of the rods, there is no
      interference with motion.

PMID- 8744429
TI  - Four radiological measures to estimate shoulder balance in scoliosis.
AB  - We studied four indirect radiological measures of shoulder balance, their
      correlation with true shoulder balance, and measurement error of each method.
      Thirty-three consecutive patients with idiopathic scoliosis requiring surgical
      treatment were selected. Actual shoulder level was determined from a line in the
      top margin of the acromion clearly visualized in the wide chart. Indirect
      references used to assess shoulder balance were tilting of cephalic end-plate of
      T1, inclination of a line through superior border of both first ribs, the level
      of top margin of coracoid processes, and the level of two specific points where
      the clavicle intersects the rib cage. All radiographs were assessed by three
      independent observers. Correlation coefficients between each measurement and true
      shoulder level were 0.54 for T1 tilting (p = 0.001), 0.63 for first rib
      inclination (p < 0.001), 0.96 for coracoid process (p = 0.0001), and 0.93 for
      clavicle-rib cage intersection (p = 0.0001).

PMID- 8744430
TI  - Congenital hypoplasia of the fibula: clinical manifestations.
AB  - We describe five cases of congenital hypoplasia of the fibula and the clinical
      appearance of the patients. The more relevant clinical manifestation is leg
      length discrepancy, which is usually < 6 cm. The management of this problem has
      been approached with predictive tables and timing of the epiphyseodesis. Some
      cases have been treated with tibial lengthening to correct the associated valgus
      deformity simultaneously. The valgus deformity is secondary to the hypoplasia of
      the lateral femoral condyle, which can be treated with medial hemiepiphysiodesis
      of the distal femur. Anterior instability of the knee usually exists due to
      congenital absence of the anterior cruciate ligament and can complicate
      lengthening procedures. The hip joint is not involved, but mild shortening of the
      femur was observed in four cases. Ball and socket joint at the ankle and tarsal
      coalitions with absent lateral rays of the foot can occur. Management of the leg
      length discrepancy must be considered in light of all these possible associated
      defects.

PMID- 8744431
TI  - Endoscopic discectomy in pediatric and juvenile lumbar disc herniations.
AB  - Most herniated lumbar discs in children and adolescents respond to conservative
      treatment, but some young patients with persistent low back and neurological
      symptoms do not respond to noninvasive treatment and require operative treatment.
      Because the long-term results of disc surgery depend not only on the disc disease
      itself but also on the degree of surgical trauma, disc herniations in children
      and adolescents should be treated with minimally invasive procedures. We report
      our experience with four young patients aged 8-17 years with contained or small
      noncontained lumbar disc herniations who were treated by percutaneous endoscopic
      discectomy (PED). The clinical results were good to excellent in all four cases,
      with follow-up of 1 to 5 years. There were no complications, and the operation
      was tolerated well by the young patients. We recommend percutaneous endoscopic
      lumbar discectomy in patients with contained or small uncontained disc
      herniations who do not respond to conservative treatment.

PMID- 8744432
TI  - Revised arthrographic index of deformity for Perthes' disease.
AB  - We report a new arthrographic index to quantitate the loss of sphericity of the
      femoral head during early Perthes' disease. The technique has been applied to 272
      arthrograms of 131 normal and 141 affected hips. It measures marginal or
      segmental collapse as well as central collapse of the epiphysis, thus providing a
      more accurate assessment of deformity in 57.4% of anteroposterior and 46.8% of
      lateral radiographs as compared with the previous standard measurement (caput
      index). The measurement principle applies equally to other recent radiological
      developments such as magnetic resonance imaging.

PMID- 8744433
TI  - Quantitative correlation between the initial and final femoral head deformity in
      Perthes' disease.
AB  - A review at maturity of 42 patients with Perthes' disease has allowed a
      correlation to be made between femoral head deformity during the initial phases
      of fragmentation and reparation, as quantified arthrographically, with the final
      shape and size of the femoral head measured on plain radiographs. Cases with loss
      of sphericity or coxa magna at maturity had significantly lower arthrographic
      indexes of deformity (p = 0.001 and p = 0.005 respectively), regardless of the
      age at presentation. All were treated uniformly by containment in recumbency and
      a daily exercise program.

PMID- 8744434
TI  - Critical aspects of neonatal surgery in clubfoot.
AB  - Good results after early operative treatment of clubfoot has been reported by
      some investigators. Most have recommended early conservative treatment and later
      surgical procedures in resistant cases. Operation immediately after birth is
      demanding, and the operative team must master all problems of neonatal surgery,
      anesthesiology, and postoperative care. Conservative treatment in experienced
      hands may lead to a satisfactory result in one third of cases. We recommend
      primarily conservative treatment, but patients with resistant cases must undergo
      operation at age 2-5 months. We need more prospective studies and generally
      accepted grading systems of results.

PMID- 8744435
TI  - Early posttraumatic physeal arrest in distal radius after a compression injury.
AB  - Early posttraumatic arrest of the distal radial physis is an uncommon
      complication and usually appears after type II physeal injury. We report a 13
      year-old boy who sustained an injury to his right wrist, incurring an avulsion
      fracture of ulnar styloid process. Twenty-one months later, a uniform closure of
      the distal radial physis was observed. An ulnar shortening osteotomy and distal
      ulnar epiphysiodesis were performed. We discuss different factors of this
      complication, but crush injury of germinal cells of the growthplate is considered
      the main etiology.

PMID- 8744436
TI  - Fracture of the occipital condyle.
AB  - We report the case of a patient with occipital condyle fracture who was
      neurologically intact. The patient was treated conservatively with a neck collar,
      and the symptoms resolved in 3 months. This diagnosis can be suspected in high
      velocity road traffic accidents, in a patient with neck pain, disproportionate
      torticollis, or lower cranial nerve symptoms. Skull radiography and cervical
      spine films can be normal. The diagnosis is best made by high-resolution computed
      tomographic (CT) scanning with sagittal and coronal reconstruction.

PMID- 8744437
TI  - Intrinsic Connections in the macaque inferior temporal cortex.
AB  - Intrinsic connections in the inferior temporal cortex were analyzed by making
      extracellular injections of biocytin in Japanese macaques. Analysis was focused
      mainly on the dorsal part of area TE, in which a functional columnar organization
      has been shown. Interlaminar connections were analyzed in coronal section after
      laminar-specific microinjections, and intralaminar connections were examined from
      tangential sections. After injections at various depths in the dorsal TE, both
      axons and cell bodies were strongly labeled above or below the injection site in
      a columnar appearance. Axons from layer 3 ran in bundles towards the white matter
      and gave off prominent collaterals in layer 5. Ascending axons from lower to
      upper layers were also present (e.g., layers 4, 5, and 6 to layer 3). In
      tangential sections, there were abundant axons running parallel to the pia mater.
      These horizontal axons, particularly those in layers 2 and 3, produced patches of
      terminals 0.5 +/- 0.1 mm (mean +/- s.d.) in size and cylindrical in shape,
      spanning layers 1-3 or even to layers 4 and 5. In the tangential plane, they were
      distributed in an anisotropic manner around the injection. The farthest patch
      appeared at 4 mm from the injection site. The center-to-center distance between
      nearest-neighbor patches was 0.7 +/- 0.3 mm. These patches were found only within
      the dorsal TE and did not extend into the lower bank of the superior temporal
      sulcus or into the ventral part of area TE. Area TEO, which is a major afferent
      source to area TE, had axonal patches with spacing similar to those in area TE
      but with smaller sizes (0.4 +/- 0.1 mm). The results show that intrinsic
      horizontal axons both in area TE and in area TEO arborize in a patchy manner, as
      has been reported for several other cortical areas. In are TE, the size and
      spacing of the terminal patches match those of columns with similar stimulus
      selectivity. Thus, these patches may be related to the functional modularity in
      area TE. Vertical connections across layers and cylindrical patches of horizontal
      axons most likely contribute to the shared stimulus selectivity among cells
      within a column.

PMID- 8744438
TI  - Organisation of the cerebellar nucleus of the dogfish, Scyliorhinus canicula L.:
      a light microscopic, immunocytochemical, and ultrastructural study.
AB  - Elasmobranchs possess a well-developed cerebellum with an associated cerebellar
      nucleus. To determine whether the organization of this nucleus is comparable with
      that of the deep cerebellar nuclei of mammals, we studied the dogfish cerebellar
      nucleus with light microscopic methods (Nissl stain, Golgi method, reduced silver
      stain, NADPH-diaphorase histochemistry and immunocytochemistry) and with electron
      microscopy. We found the dogfish cerebellar nucleus to consist of about 1,050
      large neurons, the ratio of Purkinje cells to cerebellar nucleus neurons being
      about 17:1. Immunocytochemistry showed large glutamatergic neurons in the main
      portions of the nucleus and small glutamate- and/or alpha-aminobutyric acid
      (GABA)-immunoreactive cells in the subventricular region of the nucleus. Large
      glutamatergic neurons corresponded to bipolar or triangular cells revealed by
      Golgi methods. Application of horseradish peroxidase to the cerebellar cortex
      produced the labelling of beaded fibres of Purkinje cells in the cerebellar
      nucleus. Unlike in mammals, GABAergic innervation of the cerebellar nucleus was
      scare: Purkinje cell axon terminals in the cerebellar nucleus did not appear to
      be GABA-immunoreactive, most GABAergic fibres being found in the subventricular
      neuropile. Some fibres immunoreactive to serotonin and somatostatin were also
      observed in the subventricular neuropile of the cerebellar nucleus. Three neuron
      types were distinguished with electron microscopy (types A to C). Type A cells
      were abundant and smooth-surfaced, and appeared to correspond to Golgi
      impregnated neurons and large glutamate-immunoreactive cells. Type B neurons were
      scarce and possessed dendrites covered by sessile or stalked spines. Type C
      neurons were small cells located mainly in the medialmost region of the nucleus
      and corresponded to subventricular glutamate- and GABA-immunoreactive cells. Six
      types of synaptic bouton were observed (types I to VI). The most abundant (type I
      boutons) made symmetrical contacts and appeared to correspond to Purkinje cell
      axons. Type I boutons were the only type observed on perikarya and initial axon
      segments of type A cells. Type IV and type V boutons made complex glomerular-like
      asymmetrical contacts with spines of type B cells. Type VI boutons appeared to
      correspond to peptidergic and/or monoaminergic axons. The functional significance
      of these results is discussed.

PMID- 8744439
TI  - Changes in glutamate immunoreactivity in the somatic sensory cortex of adult
      monkeys induced by nerve cuts.
AB  - Antibodies to glutamate (Glu) were used to study the effects of reduced afferent
      input on excitatory neurons in the somatic sensory cortex of adult monkeys. In
      each monkey, immunocytochemical staining was compared to thionin and cytochrome
      oxidase (CO) staining in adjacent sections. In the cervical spinal cord, dorsal
      column nuclei, ventroposterior thalamus, and primary somatic sensory cortex (SI),
      Glu immunoreactivity (Glu-ir) was analogous to that described in normal animals;
      regions with reduced or absent Glu-ir were never observed and no appreciable
      differences were noted between the experimental and normal side. There were also
      no differences in CO or thionin-stained sections from the affected hemisphere. In
      the insuloparietal operculum, sections in the hemisphere contralateral to the
      nerve cut showed that most cortical fields had a normal pattern of Glu-ir
      (pattern a), some exhibited a reduction of Glu-ir (pattern b), and that in the
      central portion of the upper bank of the central sulcus, which corresponds to the
      general location of the hand representation of the second somatic sensory cortex
      (SII), Glu-ir had virtually disappeared (pattern c). Adjacent sections processed
      for CO or stained with thionin showed that in the regions corresponding to those
      characterized by pattern c, CO was slightly decreased and that glial cells had
      increased in number. In the regions of SII characterized by pattern c, small
      intensely stained glial cells displayed Glu-ir. These findings indicate that Glu
      ir is regulated by afferent activity and suggest that changes in Glu levels in
      neurons as well as in glial cells may trigger the biochemical processes
      underlying the functional and structural changes occurring during a slow phase of
      reorganizational plasticity in the cerebral cortex of adult monkeys.

PMID- 8744440
TI  - Patterns of neuronal differentiation in neural tube mutant mice: curly tail and
      Pax3 splotch-delayed.
AB  - A battery of antibodies was used to assess development of the spinal cord and its
      neurons in mouse embryos with neural tube defects (NTDs). The two mutant strains
      examined, curly tail (ct) and splotch-delayed (Pax3Sp-d), develop an open neural
      tube for unrelated reasons, and thus provided for a complementary analysis. Five
      percent of embryos homozygous for the ct gene and 89% of embryos homozygous for
      the Pax3Sp-d gene develop spina bifida in the lumbosacral region of the neuraxis.
      Expression of several neuronal antigens, including Islet-1/2, polysialylated
      neural cell adhesion molecule (NCAM), neurofilaments, and a neuronal-specific
      nuclear protein (Neu-N) recognized by monoclonal antibody A60, were used as
      indicators of the level of differentiation of neuronal tissue.
      Immunohistochemical labeling suggests that early (embryonic days 12-15) neuronal
      differentiation in the dorsal and ventral region of the dysraphic neural tube
      occurs remarkably normally in both of the mutants. Similarly, labeling with
      antibodies to NCAM and neuroafilaments indicate that axonal development during
      early neurogenesis is unperturbed. Later stages of neuronal maturation, however,
      do not occur in the usual manner. Instead, the neuronal tissue begins a
      prodigious degeneration at embryonic day 17 (E17), so that by E18 only a
      rudimentary tissue remains. These results suggest that the aberrant morphology of
      the neural tube does not affect neuronal differentiation. However, the anomalous
      morphological and chemical environment may contribute to the neuronal
      degeneration observed at later stages.

PMID- 8744441
TI  - Annexin IV is a marker of roof and floor plate development in the murine CNS.
AB  - Midline structures, such as the notochord and floor plate, are crucial to the
      developing central nervous system (CNS). Previously, we demonstrated that annexin
      IV is an excellent marker of midline structures. In the present study, we explore
      the possible role of annexin IV in development of the CNS midline. Using
      immunocytochemistry with an antibody to annexin IV, we have elucidated the
      temporal and spatial expression of this molecule. Annexin IV is present in the
      notochord at embryonic day (E) 8.5, prior to its expression in any structures
      within the neural tube. Subsequently, annexin IV is expressed by floor plate
      cells at E9.5. Annexin IV is also expressed in the roof plate, but not until
      E10.5. To determine if normal morphogenesis of these midline structures is
      essential for annexin IV expression, we analyzed two strains of mutant mice that
      have defective formation of either the floor or the roof plate. In Danforth's
      short-tail mice, the floor plate is absent from the caudal spinal cord, and
      annexin IV immunopositivity disappears at the level where the floor plate is
      missing. In curly tail mutant mice, there can be a failure of the neural tube to
      close, and in these regions there is no annexin IV expression in presumptive roof
      plate cells. Finally, annexin IV immunolabeling is present from the caudal spinal
      cord, through the brainstem up to the diencephalon and lamina terminalis. Thus,
      annexin IV is an excellent marker for differentiated midline cells, is temporally
      and spatially correlated with development of the floor and roof plates, and is
      expressed in a rostral-caudal manner that supports the hypothesis that the floor
      plate extends the full length of the original neural tube.

PMID- 8744442
TI  - Distribution of M retinal ganglion cells in diurnal and nocturnal New World
      monkeys.
AB  - The topography of M ganglion cell distribution was studied in the retinae of two
      New World monkey species, the diurnal capuchin monkey Cebus apella and the
      nocturnal owl monkey Aotus azarae. Retinal whole mounts were stained by the
      neurofibrillar method of Gros-Schultze. As occurs with other diurnal primates,
      the Cebus M-ganglion cell density peaks in the foveal slope and declines towards
      the periphery. In the Aotus retina, the M ganglion cell density peaks in the area
      centralis and declines toward the periphery. In both species the cell density in
      the temporal, dorsal, and ventral meridians are similar for equivalent
      eccentricities. The cell density in the nasal meridian is higher than in the
      other meridians. The naso-temporal density ratio ranges between 1.2 and 4.3 in
      the Cebus and 1.6 and 2.2 in the Aotus. The total number of M-ganglion cells was
      140,300 and 74,000 in the Cebus and Aotus retinae, respectively, corresponding to
      about 10% and 15.4% of the total retinal ganglion cell population in these
      species. The results indicate that M ganglion cells are similarly organized in
      both diurnal and nocturnal simians, but may be proportionally more important for
      the nocturnal species.

PMID- 8744443
TI  - Expression of glutamate receptors in the human and rat basal ganglia: effect of
      the dopaminergic denervation on AMPA receptor gene expression in the
      striatopallidal complex in Parkinson's disease and rat with 6-OHDA lesion.
AB  - The overactivity of subthalamopallidal and corticostriatal glutamatergic neurons
      observed in Parkinson's disease (PD) suggests that antagonists of glutamate
      receptor could be used to alleviate the motor symptoms of the disease. In this
      study, we analysed two features of the striatopallidal complex: (1) the
      distribution of alpha-amino-3 hydroxy-5-methyl-4-isoxasol-propionate (AMPA) and
      kainate receptors and their corresponding mRNA by immunohistochemistry and in
      situ hybridisation and (2) the effect of dopaminergic denervation on AMPA
      receptor gene expression in PD patients and rats with 6-hydroxydopamine (6-OHDA)
      induced degeneration of the nigrostriatal dopaminergic system. All AMPA receptor
      mRNAs and proteins (GluR1-4) were detected in the internal segment of the globus
      pallidus (GPi). Among kainate receptors, only KA1 and KA2 were detectable and
      only at a low level. Only GluR4 protein was detected in the neuropil of the GPi.
      In the striatum, GluR1, GluR2, and GluR3 were detected in about 70% of medium
      sized and large neurons. By contrast, GluR4 mRNA was detected in only a small
      number of large and medium-sized neurons. Among kainate receptors, GluR6, GluR7,
      and KA2 were detected in about 50-60% of medium-sized neurons, whereas GluR5 and
      KA1 were restricted to 1-2% and 20-30% of these neurons, respectively. These
      results suggest that antagonists of AMPA and kainate receptors could be effective
      in alleviating motor symptoms in Parkinson's disease by blocking the
      overstimulation of pallidal and striatal neurons by glutamate. A significant
      decrease in GluR1 gene expression (-33%) was observed in the neurons of the GPi
      in PD patients and in rat entopeduncular nucleus ipsilateral to the 6-OHDA lesion
      (-20%). GluR2, GluR3, and GluR4 mRNA levels in the GPi and GluR1-4 levels in the
      striatum were unchanged in PD patients and 6-OHDA-lesioned rats compared with
      their respective controls. These data suggest that dopamine positively regulates
      only GluR1 gene expression in the GPi.

PMID- 8744444
TI  - Neurofilament spacing, phosphorylation, and axon diameter in regenerating and
      uninjured lamprey axons.
AB  - It has been postulated that phosphorylation of the carboxy terminus sidearms of
      neurofilaments (NFs) increases axon diameter through repulsive electrostatic
      forces that increase sidearm extension and interfilament spacing. To evaluate
      this hypothesis, the relationships among NF phosphorylation, NF spacing, and axon
      diameter were examined in uninjured and spinal cord-transected larval sea
      lampreys (Petromyzon marinus). In untransected animals, axon diameters in the
      spinal cord varied from 0.5 to 50 microns. Antibodies specific for highly
      phosphorylated NFs labeled only large axons (> 10 microns), whereas antibodies
      for lightly phosphorylated NFs labeled medium-sized and small axons more darkly
      than large axons. For most axons in untransected animals, diameter was inversely
      related to NF packing density, but the interfilament distances of the largest
      axons were only 1.5 times those of the smallest axons. In addition, the lightly
      phosphorylated NFs of the small axons in the dorsal columns were widely spaced,
      suggesting that phosphorylation of NFs does not rigidly determine their spacing
      and that NF spacing does not rigidly determine axon diameter. Regenerating
      neurites of giant reticulospinal axons (GRAs) have diameters only 5-10% of those
      of their parent axons. If axon caliber is controlled by NF phosphorylation via
      mutual electrostatic repulsion, then NFs in the slender regenerating neurites
      should be lightly phosphorylated and densely packed (similar to NFs in uninjured
      small caliber axons), whereas NFs in the parent GRAs should be highly
      phosphorylated and loosely packed. However, although linear density of NFs (the
      number of NFs per micrometer) in these slender regenerating neurites was twice
      that in their parent axons, they were highly phosphorylated. Following sectioning
      of these same axons close to the cell body, axon-like neurites regenerated
      ectopically from dendritic tips. These ectopically regenerating neurites had NF
      linear densities 2.5 times those of uncut GRAs but were also highly
      phosphorylated. Thus, in the lamprey, NF phosphorylation may not control axon
      diameter directly through electrorepulsive charges that increase NF sidearm
      extension and NF spacing. It is possible that phosphorylation of NFs normally
      influences axon diameter through indirect mechanisms, such as the slowing of NF
      transport and the formation of a stationary cytoskeletal lattice, as has been
      proposed by others. Such a mechanism could be overridden during regeneration,
      when a more compact, phosphorylated NF backbone might add mechanical stiffness
      that promotes the advance of the neurite tip within a restricted central nervous
      system environment.

PMID- 8744445
TI  - Transient retinal ganglion cells in the developing rat are characterized by
      specific morphological properties.
AB  - To determine whether dendritic development of mammalian retinal ganglion cells
      (RGCs) is affected by axonal target specificity, the morphology of three
      populations of maturing RGCs was examined. These included RGCs that exhibited
      either a transient, topographically incorrect, projection to the caudal superior
      colliculus (SC), or a transient projection to the caudal inferior colliculus
      (IC), in addition to a control group that exhibited a topographically correct
      projection to the caudal SC. Projection populations were identified by retrograde
      transport of rhodamine labeled latex microspheres injected into target nuclei.
      Labeled RGCs were then injected in vitro with Lucifer yellow to reveal the
      details of their dendritic morphology. Retinal ganglion cells making target
      errors, most of which ultimately die, were found to undergo a remarkable degree
      of morphological differentiation and could be categorized according to the adult
      type I, II, or III criteria. However, the relative proportions of these cell
      types were different among RGCs making transient connections versus those whose
      projections were preserved. Approximately half of the RGCs making topographically
      incorrect projections to the SC belonged to type III, in contrast to 6% that made
      a topographically correct projection. In addition, the population of cells
      sending axons to caudal IC did not include type III RGCs, but consisted of small
      type II neurons. The development of the basic dendritic form of each RGC type was
      only modestly influenced by its projection pattern; dendritic trees of cells
      making transient projections were essentially normal with only a slight, but
      statistically significant, reduction in dimensions. Moreover, dendritic
      remodeling was evident during maturation of neurons making either transient or
      normal projections. Together, these findings indicate that target specificity
      plays a relatively minor role on dendritic development of retinal ganglion cells.

PMID- 8744446
TI  - Cellular localization of Pan-trk immunoreactivity and trkC mRNA in the enteric
      nervous system.
AB  - The members of the trk family of tyrosine receptor kinases, trkA, trkB, and trkC,
      are the functional receptors for neurotrophins, a family of related neurotrophic
      factors. In this study, we investigated 1) the distribution of neurotrophin
      receptors in the developing and adult rat digestive tract with a pan-trk antibody
      that recognizes all known trks and 2) the cellular localization of trk-encoding
      mRNAs in the adult gut with single-stranded RNA probes specific for trkA, trkB,
      and trkC. In the developing myenteric plexus, trk immunoreactivity was present at
      embryonic day (ED) 14. Cells and fibers immunoreactive for trk could be
      visualized in the myenteric plexus at ED 16. At this age, dense staining was
      found in thick bundles of fibers in proximity to the myenteric plexus in the
      longitudinal muscle and in association with blood vessels in the mesentery. At ED
      18, trk immunoreactivity was also seen in thin processes running from the
      myenteric plexus into the circular muscle, and in fibers and cells in
      intrapancreatic ganglia. By ED 20, immunoreactive staining was quite dense in
      both the myenteric and submucosal plexuses. At birth, virtually all enteric
      ganglia displayed strong trk immunoreactivity; the intensity of the staining at
      this age made it difficult to discern individual cells. During postnatal
      development, there was a decrease in cell body staining and an increase in the
      density of trk-containing fibers that became widely distributed to the gut wall
      and pancreas. The adult pattern of trk immunoreactivity was established between
      postnatal days 5 and 10. In adults, trk immunoreactivity was found in numerous
      enteric and intrapancreatic ganglion cells and in dense networks of fibers
      innervating all the layers of the gut, the pancreas, and vasculature. The trkC
      mRNA was expressed in adult enteric ganglion cells of both the myenteric and
      submucous plexus. By contrast, the trkA and trkB mRNAs could not be detected in
      enteric ganglia. All three trk mRNAs were expressed in dorsal root ganglia, which
      were used as positive controls. The density and wide distribution of trk
      immunoreactivity together with its persistence in adulthood support the concept
      that neurotrophins play a broad role in the digestive system from development
      through adult life, perhaps being involved in differentiation, phenotypic
      expression, and tissue maintenance. The presence of trkC mRNA in enteric neurons
      along with recent evidence that neurotrophin-3 plays a role in the development of
      the enteric nervous system suggest that trkC and neurotrophin-3 are a major
      neurotrophin system in the gastrointestinal tract.

PMID- 8744447
TI  - Projections from the cerebellar interposed and dorsal column nuclei to the
      thalamus in the rat: a double anterograde labelling study.
AB  - It is generally agreed that cerebellar and lemniscal pathways project to largely
      separate areas of the thalamus and influence different functional areas of the
      cerebral cortex. Cerebellar afferents arise from neurones in the deep cerebellar
      nuclei and terminate in the ventral lateral group of thalamic nuclei or the
      "motor thalamus," whereas lemniscal afferents arise from the dorsal column nuclei
      and terminate in the adjacent ventral posterior group of thalamic nuclei or
      "sensory thalamus." However, it remains unclear whether or not these pathways
      converge onto thalamic neurones in the border zone between motor and sensory
      thalamus. The aim of this study was to compare directly the locations of
      cerebellar interposed and dorsal column nuclei terminals in the rat thalamus by
      using a double anterograde labelling technique. Microinjections of dextran
      tetramethylrhodamine and dextran-fluorescein were made into the interposed and
      dorsal column nuclei, and labelled terminals in the thalamus were examined in the
      same sections. The labelled cerebellar and lemniscal terminals were located in
      separate areas throughout most of the ventral lateral and ventral posterior
      lateral nuclei, and there was only a limited region around the rostral border
      between these nuclei where the two groups of terminals came in close proximity to
      each other. In this common projection zone, however, cerebellar and lemniscal
      terminals seldom intermingled, and they mostly occupied separate, discreet areas.
      The results show that cerebellar and lemniscal fibres do indeed project to the
      border zone between the sensory and cerebellar thalamic nuclei, but they show
      practically no overlap in this region and are likely to influence separate
      thalamic neurones.

PMID- 8744449
TI  - Formularies and generics drive up health resource use, study suggests.

PMID- 8744448
TI  - Standard atlas of the gross anatomy of the developing inner ear of the chicken.
AB  - During development, the chicken inner ear undergoes a series of morphological
      changes which give rise to the various structures found in the adult, including
      the mature semicircular canals, utricle, saccule, cochlear duct, endolymphatic
      duct and sac, and neurons of the eighth cranial nerve ganglion. Beginning as a
      hollow epithelial sphere, the inner ear is sculpted into this complex labyrinth
      of fluid-filled ducts punctuated by their associated sensory end organs. In this
      report, the three-dimensional complexity of the developing inner ear of the
      chicken embryo is documented in the form of a standard atlas. The protocol
      involved fixation, dehydration, and clearing of embryonic heads harvested at
      daily intervals, followed by injection of an opaque dye (enamel paint suspension)
      into the fluid ducts of the inner ear. The position of the ear is shown relative
      to surface landmarks at seven different stages of development, ranging from
      embryonic day 5 (E5) to E18. Also shown are higher-power photomicrographs of the
      inner ear in isolation taken at daily intervals at E3-E17 and viewed from two
      orthogonal positions. Three orthogonal views are shown at 6-hour intervals during
      the critical stages of semicircular canal formation (E6-E7). Quantitative
      measurements of the linear dimensions of the inner ear (dorsoventral,
      anteroposterior, and mediolateral axes) as a function of time indicate a linear
      increase in the growth of the ear from E3 through E18. This atlas should prove
      valuable for evaluating mutant phenotypes in inner ear morphogenesis following
      gene perturbation experiments in the chicken.

PMID- 8744450
TI  - Studies raise possibility of home therapy for acute deep-vein thrombosis.

PMID- 8744451
TI  - Home care company is single source for purchase of epoprostenol.

PMID- 8744452
TI  - Indinavir marketed under accelerated-approval program.

PMID- 8744453
TI  - Nicotine nasal spray is newest smoking cessation aid.

PMID- 8744454
TI  - Postmarketing surveillance indicates need for better education of patients taking
      alendronate.

PMID- 8744455
TI  - APhA adopts policies on vaccines, quality improvement, technician registration.

PMID- 8744456
TI  - New recommendations address acute diarrhea in children.

PMID- 8744457
TI  - New content-specific continuing-education requirements.

PMID- 8744458
TI  - Establishing a new pharmacy network or using a PBM for HMO prescriptions.

PMID- 8744459
TI  - Implications of multitier pricing.

PMID- 8744460
TI  - Bolstering requests for more personnel.

PMID- 8744461
TI  - Pharmacists and stroke prevention.

PMID- 8744462
TI  - Pharmacists' provision of continuity of care to patients with human
      immunodeficiency virus infection.
AB  - A pharmacy program for providing continuity of care to patients infected with
      human immunodeficiency virus (HIV) is described. The program was implemented at
      three practice sites in Toronto: a tertiary care teaching hospital; an outpatient
      community pharmacy that is part of the hospital; and an ambulatory care clinic
      affiliated with the hospital. An HIV pharmacy practice was established at the
      hospital in 1993. The community pharmacy serves at least 30% of the HIV-infected
      patients in Ontario who are receiving antiretrovirals; patient counseling is
      emphasized. The ambulatory care clinic's HIV program was established in 1994; the
      pharmacist sees patients at the clinic or in their homes. To address the need for
      greater continuity of care, the following issues were addressed: workload
      involved in providing pharmaceutical care to HIV-infected patients, establishing
      patient pharmacy profiles common to the three sites, streamlining communication
      among the sites, creating a process for identifying patient problems in the
      community setting, collaborating on research and projects, and forging links with
      other pharmacists caring for HIV-infected patients. The program has enhanced the
      ability of pharmacists to make informed recommendations and care plans, increased
      patient follow-up, improved cross-coverage of patients in the absence of an HIV
      pharmacist, increased sharing of drug information, and led to joint collaboration
      on projects. A pharmacy program to serve HIV-infected patients was implemented at
      three sites and successfully integrated under a continuity-of-care model.

PMID- 8744463
TI  - Ambulatory care certificate program for pharmacists.
AB  - An ambulatory care certificate program tailored to meet the educational needs of
      Department of Veterans Affairs (VA) and Navy pharmacists is described. In 1992,
      the College of pharmacy, University of Illinois at Chicago, worked with the VA
      and the Navy to design an ambulatory care certificate program for pharmacists in
      VA and Navy hospitals. The pilot course consisted of 103 hours of didactic and
      experiential education. The 10 didactic modules covered both disease management
      and clinical skills. The experiential component incorporated pharmaceutical care
      steps as applied to therapeutic areas taught in the course. Although the pilot
      course met most of the original objectives, several unanticipated problems
      emerged, including distance learning issues, the number of hours for completing
      the course requirements, learner variance, the impact of institutional support on
      participants' academic success, participants' difficulty in assimilating
      education into practice, and difficulty with the clinical evaluation tool
      developed for the course. The course was modified over the next year to address
      these problems. Now in its fourth year, the course is offered nationally to the
      VA and the Department of Defense. In the first three years, 72 of 99 enrolled
      pharmacists completed the course. An ambulatory care certificate program helps
      Navy and VA pharmacists develop patient care skills.

PMID- 8744464
TI  - Serum bactericidal activity of ceftizoxime and ceftriaxone against pathogens
      associated with community-acquired and nosocomial pneumonias.
AB  - The serum bactericidal activities of ceftizoxime and ceftriaxone against
      organisms commonly implicated in community-acquired and nosocomial pneumonias
      were studied. Ceftizoxime 1 g (as the sodium salt) every 12 hours for two doses
      and ceftriaxone 1 g (as the sodium salt) every 24 hours for two doses were
      administered to 20 healthy volunteers in a crossover fashion. Blood samples were
      drawn immediately before and 2,4,6,8,10, and 12 hours after the second
      ceftizoxime dose and immediately before and 8,12,16,18,20, and 24 hours after the
      second ceftriaxone dose. Serum drug concentrations were determined by validated
      high-performance liquid chromatography. Serum bactericidal titers were determined
      in duplicate for each serum sample against four clinical isolates of each of the
      following organisms: Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus
      influenzae, Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, and
      Serratia marcescens. The median duration of serum bactericidal activity during
      the dosage interval was significantly different between antimicrobial regimens
      only for S. pneumoniae (92% of the dosage interval for ceftizoxime, versus 100%
      for ceftriaxone). This difference does not appear to be clinically important
      since ceftizoxime provides adequate serum bactericidal activity for more than 50%
      of the dosage interval and its effectiveness against pneumococcal pneumonia has
      been supported in clinical trials. The ceftriaxone and ceftizoxime regimens did
      not differ significantly in their duration of serum bactericidal activity against
      six of the seven organisms tested.

PMID- 8744465
TI  - Comparison of creatinine clearance estimation methods in patients with trauma.
AB  - The abilities of a modified Cockcroft-Gault equation and the standard equation to
      estimate creatinine clearance (CLcr) in trauma patients were compared. The
      medical records of patients with stable renal function who had been treated for
      trauma and had had a 24-hour urine collection for creatinine measurement were
      reviewed. Creatinine concentrations in urine and serum were used to calculate the
      actual CLcr, which was normalized to 1.73 sq m. CLcr was estimated by the
      modified equation (which normalized body weight to 72 kg) and by the standard
      equation using ABW, IBW, and dosing body weight (DBW). Values derived with the
      standard equation were normalized to 1.73 sq m. The predictive performances of
      the modified and standard equations in estimating the actual CLcr were then
      compared. Fifty patients were enrolled. The standard equation using IBW or DBW
      produced estimates that differed significantly from the actual CLcr. The modified
      equation and the standard equation using ABW did not differ significantly in bias
      or precision, but both were significantly less biased than the standard equation
      using IBW or DBW. The only significant difference among equations in precision
      was between the modified equation (the more precise) and the standard equation
      using IBW. There were no clinically significant differences among methods in
      gentamicin dosing simulations. The modified Cockcroft-Gault equation can be used
      to estimate CLcr in trauma patients with stable renal function.

PMID- 8744466
TI  - Comparison of Department of Veterans Affairs pharmacy services in 1992 and 1994
      with strategic-planning goals.
AB  - Data were collected from Department of Veterans Affairs (VA) medical center
      pharmacies in 1992 and 1994 to measure progress toward implementation of the VA
      1990 strategic plan. A questionnaire was pretested and mailed to pharmacy chiefs
      at all 173 VA medical centers (VAMCs) with pharmacies in 1992. The same
      questionnaire, with slight modifications consistent with revision of the
      strategic plan, was mailed in 1994. Usable responses were received from more than
      80% of VAMCs in both years. The number and types of activities, services, and
      staffing at VAMC pharmacies varied with respect to automation, procurement, drug
      accountability, image, participation in professional organizations, professional
      role, pharmaceutical care activities, technicians, and research and education.
      Compared with the 1992 results, the 1994 results indicated greater pharmacist
      involvement in patient-education activities, expanded roles for pharmacists in
      monitoring anticoagulation therapy and in pharmacokinetic services, and less use
      of pharmacists for distributive functions. In 1994, more facilities reported
      having an open pharmacy concept in place to encourage direct patient care
      initiatives. VAMCs reported greater involvement in pharmacy education in 1994
      than in 1992, with more VAMCs having affiliations with pharmacy schools and
      clerkship and residency training programs. Responses indicated considerable
      variation among VAMC pharmacies in the number and types of services provided.

PMID- 8744467
TI  - Compatibility of thiotepa (lyophilized) with selected drugs during simulated Y
      site administration.
AB  - The compatibility of lyophilized thiotepa injection with selected other drugs
      during simulated Y-site injection was evaluated. Five-milliliter samples of
      thiotepa (lyophilized) 1 mg/mL in 5% dextrose injection were combined with 5 mL
      each of 100 other drugs, including antineoplastics, anti-infectives, and
      supportive care drugs, in 5% dextrose injection or 0.9% sodium chloride
      injection. The combinations were stored at room temperature (approximately 23
      degrees C) under constant fluorescent light. Visual examinations were performed
      immediately and at one and four hours with the unaided eye and, if there was no
      obvious incompatibility, with a high-intensity mono-directional light beam to
      enhance visualization of small particles and low-level turbidity. The turbidity
      of each combination was measured as well. Particle sizing and counting were
      performed on selected solutions. Most of the test drugs were compatible with
      thiotepa 1 mg/mL during the observation period. Two drugs exhibited
      incompatibilities with thiotepa. The thiotepa-cisplatin combination developed
      turbidity in four hours, and the thiotepa-minocycline hydrochloride combination
      developed a bright yellow-green discoloration in one hour. All the test drugs
      except cisplatin and minocycline hydrochloride were compatible with thiotepa 1
      mg/mL (prepared from the lyophilized formulation) for at least four hours at room
      temperature.

PMID- 8744468
TI  - Stability of metronidazole and ceftizoxime sodium in ready-to-use metronidazole
      bags stored at 4 and 25 degrees C.

PMID- 8744469
TI  - Compatibility of selected critical care drugs during simulated Y-site
      administration.

PMID- 8744470
TI  - Needlestick injuries and hazardous drugs.

PMID- 8744471
TI  - Milrinone in patients awaiting heart transplantation.

PMID- 8744472
TI  - Medication errors--beyond frequency.

PMID- 8744473
TI  - Unsubstantiated maligning of pharmacists who compound.

PMID- 8744474
TI  - The State of the Science in Autism. Conference proceedings. Bethesda, Maryland,
      April 1995.

PMID- 8744475
TI  - State of the science in autism: report to the National Institutes Health.

PMID- 8744476
TI  - Brief report: diagnostic issues in autism: results of the DSM-IV field trial.

PMID- 8744477
TI  - Brief report: comorbid psychiatric disorders of autistic disorder.

PMID- 8744478
TI  - Brief report: epidemiology of autism.

PMID- 8744479
TI  - Brief report: current theory and research on language and communication in
      autism.

PMID- 8744480
TI  - Brief report: communication, language, social, and emotional development.

PMID- 8744481
TI  - Brief report: neuropsychology of autism: a report on the state of the science.

PMID- 8744482
TI  - Brief report: response to National Institutes of Health report.

PMID- 8744483
TI  - Brief report: developmental neurobiological aspects of autism.

PMID- 8744484
TI  - Brief report: genetic, prenatal, and immunologic factors.

PMID- 8744485
TI  - Brief report: neuroanatomic observations of the brain in pervasive developmental
      disorders.

PMID- 8744486
TI  - Brief report: brain mechanisms in autism: functional and structural
      abnormalities.

PMID- 8744487
TI  - Brief report: neuroimaging in autism: the state of the science 1995.

PMID- 8744488
TI  - Brief report: medial temporal lobe and autism: a putative animal model in
      primates.

PMID- 8744489
TI  - Brief report: pathophysiology of autism: neurochemistry.

PMID- 8744490
TI  - Brief report: the role of National Brain and Tissue Banks in research on autism
      and developmental disorders.

PMID- 8744491
TI  - Brief report: psychopharmacology of autism spectrum disorders.

PMID- 8744492
TI  - Brief report: alternative approaches to the development of effective treatments
      for autism.

PMID- 8744493
TI  - Brief report: early intervention in autism.

PMID- 8744494
TI  - Brief report: the case for social and behavioral intervention research.

PMID- 8744495
TI  - Brief report: a life-span perspective on the development of individuals with
      autism.

PMID- 8744497
TI  - Collaboration between research professional and consumer.

PMID- 8744496
TI  - Autism research: prospects and priorities.
AB  - Research prospects and priorities in the field of autism are discussed with
      respect to (a) diagnosis, classification, and epidemiology; (b) clinical
      research; (c) neuropsychological research; (d) genetics; (e) structural and
      functional brain imaging; (f) postmortem studies; (g) other biological research;
      and (h) treatment research. Also, it is argued that research into autism has a
      priority in the broader field of developmental psychopathology because it carries
      the promise of throwing light on casual mechanisms that apply beyond the syndrome
      of autism.

PMID- 8744498
TI  - Sonographic evaluation of benign and malignant breast lesions.
AB  - Sonography can be used for the accurate differentiation of many benign and
      malignant solid breast lesions. However, considerable experience, and close
      correlation with the physical examination and the mammogram, are required to do
      so. Sixteen sonographic signs useful in this differentiation are reviewed. The
      specific sonographic appearances of the most common being entities are described.
      Primary breast malignancies are divided into five categories according to their
      sonographic presentations: (1) classic neoplasms with irregular borders, echoic
      rims, and usually posterior shadowing, (2) small, round neoplasms with no echoic
      rim or posterior shadowing, (3) neoplasms with mixed or increased echogenicity,
      (4) cystic or intracystic carcinomas, and (5) colloid carcinomas. Methods for
      identification of these different types of invasive malignancy, and of in situ
      carcinomas, are presented. The usefulness of sonomammography is considered in
      specific circumstances, including evaluation of mammographic or physical
      findings, dense breasts, post-radiation breasts, and women under 35 years of age.

PMID- 8744499
TI  - Three-dimensional fluorescence in situ hybridization. Chromosomal studies on
      nuclei from cytogenetic preparations by confocal microscopy.
AB  - OBJECTIVE: To determine the three-dimensional (3D) position of target sequences
      and chromosomal volumes in interphase human nuclei by confocal laser scanning
      microscopy (CLSM) by using the heterochromatin part of the long arm of human
      chromosome Y (HPLAHC) as a target for specific DYZ1 probes, then by D10Z1 probes
      specific to the centromere of chromosome 10. STUDY DESIGN: Fluorescence in situ
      hybridization information inside chromosomal preparations was obtained with FITC
      labelled probes and propidium iodide (PI) as a DNA-specific stain. To have a
      control in the experiment, HPLAHC Y was taken as a model of a domain and the
      centromere of chromosome 10 as a model of a single centromere spot. To have
      access to their 3D visualization, we selected FITC and PI patterns of
      fluorescence when optical slices were obtained and used a 3D reconstruction
      software. RESULTS: Labelling of the target by the probes was characteristic of Y
      heterochromatin and chromosome 10 centromere localizations and allowed
      observation of their domain in the x, y and z directions. CONCLUSION: This work
      was performed on two sets of 30 stained interphase nuclei. Deformations were
      confirmed by fluorescent spherical beads mounted in the same medium and scanned
      in the same conditions.

PMID- 8744500
TI  - Cytometry with DAPI-stained tumor imprints. A reliable tool for improved
      intraoperative analysis of lung neoplasms.
AB  - OBJECTIVE: To determine the feasibility and potential use of application of 4'-6
      diamidino-2-phenylindole dihydrochloride-stained imprints taken from primary lung
      carcinomas for intraoperative frozen section service. STUDY DESIGN: Tumor
      imprints taken from intraoperative sections were stained with the fluorochrome
      DAPI, and the integrated nuclear fluorescence (INF) was measured using an
      automated image analyzing system. The 40 cases studied comprised all major lung
      carcinoma types as well as intrapulmonary metastases. The measured features
      included percentage of tumor cells > 3C and > 5C, S-phase-related tumor cell
      fraction, 2 CV standard deviation and INF entropy. RESULTS: Test series with
      imprints of tumor-free lymph nodes revealed a minimum staining time of five
      minutes at 40 degrees C that led to reproducible staining intensities and size of
      the nuclear area. No significant differences were apparent in comparison to
      concomitantly performed measurements of the integrated optical density of
      "classical" Feulgen-stained specimens for each case. The fluorometric results
      could be submitted to the surgeon with 15-18 minutes (20 maximum). CONCLUSION:
      The data indicate that cytometric DNA measurements can be performed
      intraoperatively with reliable quality within time schedules acceptable for
      intraoperative surgical strategies.

PMID- 8744501
TI  - Differentiation of low grade non-Hodgkin's lymphoma by digital image processing.
AB  - OBJECTIVE: To identify different types of low grade B-cell non-Hodgkin's lymphoma
      (NHL) classified according to the Revised European American Lymphoma and Kiel
      classification systems by means of digital image processing. STUDY DESIGN:
      Seventy-four touch imprints were scanned and analyzed. To compare common but
      intricate DNA stain with a routinely used panoptical dye, all lymphoma specimens
      had been stained by the Romanowsky-Giemsa method and 48 touch imprints redyed
      with Feulgen-Azure A. In both cases 30 features derived from size, and chromatin
      texture of each nucleus were evaluated. RESULTS: Feulgen-stained touch imprints
      showed a 59% average probability of correct identification. The division of
      mantle cell lymphoma and chronic lymphocytic leukemia was difficult. In contrast,
      it was possible to distinguish all different types of lymphomas investigated if
      Romanowsky-Giemsa stain was used. Correct diagnoses were achieved for mantle cell
      lymphoma in 87.5%, follicle center cell lymphoma in 78%, chromic lymphocytic
      leukemia in 78%, immunocytoma in 75% and marginal zone B-cell lymphoma in 80%.
      CONCLUSION: The application of texture analysis is feasible in the classification
      of NHL.

PMID- 8744502
TI  - Computer-assisted morphometric analysis of the heart.
AB  - OBJECTIVE: To assess the applicability of the image analyzer for morphometric
      study of cardiomyopathies. STUDY DESIGN: A computer-assisted methodology for the
      morphometric study of ischemic cardiomyopathy, dilated cardiomyopathy and right
      ventricular dysplasia. RESULTS: In each heart, 200 nuclear lengths and myocyte
      diameters, 160 fields for nuclear density, 420 fields for interstitial fibrosis
      and 350 fields for replacement fibrosis were evaluated. In ischemic
      cardiomyopathy, the multiple foci of replacement fibrosis of the myocardium, in
      addition to interstitial fibrosis, appear to be the major cause of ventricular
      remodelling. In dilated cardiomyopathy the major pathologic processes are myocyte
      cell death and segmental, replacement and interstitial fibrosis. In right
      ventricular dysplasia the heart develops congestive failure due to a conspicuous
      increase in the volume of the right ventricle without an appreciable loss of the
      number of myocytes. CONCLUSION: The traditional morphometric methods based on
      test grids for the study of pathologic hearts can be enhanced using an image
      analyzer. In this way one can study a large area of the myocardium and collect a
      very large number of data. This may be the method of choice for analyses of
      pathologic human hearts.

PMID- 8744503
TI  - Relationship between adipose stromal-vascular cells and adipocytes in human
      adipose tissue.
AB  - OBJECTIVE: To determine the relative amounts of RNA and DNA from adipocytes and
      adipose stromal-vascular cells to better assess differential gene expression for
      estrogen receptor and cytochrome P450 aromatase in the two cell fractions of
      adipose tissue. STUDY DESIGN: Colorimetric and fluorometric assays were used to
      measure total RNA and DNA, and the relative cell numbers as well as the relative
      contribution of RNA from adipocytes and stromal-vascular cells were assessed.
      RESULTS: Adipocytes and stromal-vascular cells exist in a ratio of 2/1. RNA/DNA
      ratios are the same in the two cell fractions. CONCLUSION: In human subcutaneous
      adipose tissue, adipocytes are twice as numerous as stromal-vascular cells. The
      overall transcriptional activity of the cell types appears similar.

PMID- 8744504
TI  - DNA measurement in pituitary adenomas assessed on imprints by image analysis.
AB  - OBJECTIVE: To determine the DNA content and S-phase fraction (SPF) of pituitary
      adenomas by image analysis and to correlate them with clinical and morphologic
      parameters. STUDY DESIGN: The study group consisted of 26 prospectively collected
      cases of operated pituitary adenomas (3 microadenomas and 23 macroadenomas). The
      tumors were classified by histology, immunocytochemistry and electron microscopy.
      DNA measurement was performed on imprints from fresh pituitary tissue. Samples of
      nontumorous adenohypophysial parenchyma served as normal controls. RESULTS:
      Overall, 31% of adenomas, all but one functioning one, were aneuploid. The
      remaining nonfunctioning aneuploid tumor was a null cell adenoma with
      glycoprotein differentiation. All aneuploid tumors were macroadenomas, mostly at
      advanced stages, III and IV. Dural invasion, although frequent in macroadenomas
      (78%), was not correlated with DNA ploidy and SPF. An increased number of
      hyperpentaploid aneuploid cells was noted primarily in aneuploid tumors. The mean
      SPF was < 2.50%, with a statistically significant difference between aneuploid
      and diploid adenomas (3.60% vs. 1.70%). CONCLUSION: The results suggest that
      quantitative assessment of DNA content may provide important information,
      particularly in functioning adenomas. In addition, fresh tissue imprints
      represent excellent material for optimum cytometric measurements by image
      analysis systems, even for microadenomas.

PMID- 8744505
TI  - Stereologic estimation of breast tumor size.
AB  - OBJECTIVE: The largest tumor diameter, D(T), is a variable of great clinical
      value in breast cancer but a biased and imprecise estimator of real tumor size.
      Three-dimensional, shape-independent estimates would more realistically reflect
      the tumor bulk and provide more accurate clinical staging. For experimental
      oncology, the measurements may be useful for precise assessment of tumor burden.
      STUDY DESIGN: In 64 prospectively collected breast cancers, unbiased stereology
      was used for estimating the gross tumor volume, V(T), cutting specimens into
      parallel, equally thick sections with subsequent determination of total tumor
      sectional area. For comparison, the volume of invasive tumor epithelium,
      "V"(epi), was obtained by microscopic examination of systematically sampled
      tissue fractions of the same tumors, embedded in both methacrylate and paraffin.
      RESULTS: The median D(T) was 2.2 cm, and the median V(T) was 6.72 cm3. The
      correlation between these variables was not very close (r = .77), and the slope
      of the regression line was steeper than expected, presumably reflecting a change
      in tumor shape with growing size. The sampling scheme used for estimation of V(T)
      proved highly efficient, yielding a mean error coefficient of 9%. The median
      "V"(epi) in methacrylate was 1.19 cm3, 21% larger than in paraffin. Estimates of
      "V" (epi) were highly reproducible (r = .97) and correlated highly with point
      counting-based estimates of the feature (r = .96). "V"(epi) correlated with V(T)
      (r > or = .75), but the slopes of the regression lines were steeper than
      expected, corresponding with the correlation found between epithelial volume
      fraction and tumor size (r = .26). On average, about 25% of the gross tumor was
      composed of invasive epithelium, but with a wide range. CONCLUSION: In breast
      cancer, realistic estimates of tumor volume, volume of invasive epithelium and
      epithelial volume fraction can be obtained by efficient stereologic techniques,
      which seem useful for clinical and experimental oncology. In the present
      methodologic study, baseline data were generated. Further studies are needed to
      assess the clinical value of stereologic tumor size estimates as compared with
      traditional staging parameters.

PMID- 8744506
TI  - Grading and prognosis of infiltrating ductal breast carcinoma by mean nuclear
      volume estimates.
AB  - OBJECTIVE: Quantitative evaluation of nuclear size in breast cancer is performed
      with the aim of investigating whether the data obtained are related to subjective
      grading and prognosis. STUDY DESIGN: Unbiased stereologic estimates of the volume
      weighted mean nuclear volume (nuclear vv) in paraffin-embedded tissue from 44
      specimens of infiltrating ductal breast carcinoma were obtained by the point
      sampled intercepts method. RESULTS: Histologically graded cases showed an overlap
      in nuclear vv estimates, but significant differences were demonstrated in which
      averaged values increased from grade 1 to 3 breast carcinomas. Nuclear vv
      estimates in grade 3 breast carcinoma (mean, 495.4 microns 3; SD, 101.7 microns
      3) were significantly larger than those in grades 1 (mean, 327.8 microns 3; SD,
      90.9 microns 3) and 2 (mean, 409.9 microns 3; SD, 72.6 microns 3) (P < .01).
      Minor statistically significant differences (P < .05) were found between grades 1
      and 2. Estimates of nuclear vv based on systematic sampling within the specimen
      showed high efficiency, with > 80% of the total observed variance contributing to
      biologic differences between individual specimens. Univariate prognostic study
      showed that clinical stage, and not histologic grade, was of prognostic value in
      the cases studied. Similarly, nuclear vv estimates were associated with disease
      recurrence and survival, with a cutoff point of 425 microns 3. CONCLUSION: Based
      on the cases investigated, shape-independent nuclear vv estimates may be an
      adjuvant tool in the grading and prognostic evaluation of infiltrating ductal
      breast carcinoma.

PMID- 8744507
TI  - Quantification of nuclear pleomorphism using an asymptotic fractal model.
AB  - OBJECTIVE: Nuclear pleomorphism (nuclear membrane irregularity) was investigated
      using transmission electron microscope (TEM) micrographs of 1,419 nuclei (32 oral
      carcinomas and normal cells from surgical margins). STUDY DESIGN: Nuclear
      profiles (1,400 x) were digitized (1 pixel = 35 nm) and fractal dimension
      estimated using the "yardstick" method. RESULTS: Log-log plots of yardstick
      length vs. perimeter showed a significant effect on length measurement typical of
      fractals at low resolutions (large yardsticks), but this effect disappeared at
      higher resolution (small yardsticks); that is compatible with Rigaut's asymptotic
      fractal model. Analysis of the asymptotic fractal parameters c, L and Bm showed
      that c was higher in normal nuclei, but log(L) and Bm were higher in malignant
      nuclei. A linear discriminant analysis using c, log(L) and Bm reclassified
      correctly 78.8% of the nuclei (normal 88.0%, tumor 70.2%). CONCLUSION: Asymptotic
      fractal analysis of nuclear profiles appears to show great potential for
      quantitative discrimination of oral cancer cell features.

PMID- 8744508
TI  - Knowledge-guided histometry of the basal cell layer in prostatic intraepithelial
      neoplasia.
AB  - OBJECTIVE: To define a procedure for the fully automated evaluation of
      histopathologic sections of prostatic intraepithelial neoplasia. STUDY DESIGN:
      The design is based on expert system-guided scene segmentation, the construction
      of a knowledge file and the defining of histometric measures for assessment of
      the basal cell layer. RESULTS: A knowledge file specifying a total of 263
      entities was constructed. Of 73 multimegapixel-sized images of cribriform glands,
      71 were correctly and completely processed. A histometric measure allowing
      precise indexing of the degree of lesion progression, based on the deterioration
      of the basal cell layer, was derived. CONCLUSION: The combination of image
      analytic and immunohistochemical procedures and fully automated processing
      provides a quantitative measure for evaluating prostatic intraepithelial
      neoplasia lesion progression and the effects of intervention.

PMID- 8744509
TI  - The environmental risk factors associated with medical and dental equipment in
      the transmission of Burkholderia (Pseudomonas) cepacia in cystic fibrosis
      patients.
AB  - Transmission of Burkholderia (Pseudomonas) cepacia by close contact with
      colonized patients is well documented, and minimizing social contact between
      cystic fibrosis (CF) patients by segregation and cohorting of B. cepacia
      colonized patients has achieved some success in controlling the nosocomial and
      community spread of this organism. However, direct and indirect environmental
      transmission still occurs. There is evidence for transmission of B. cepacia to CF
      patients via pulmonary test equipment, nebulizers and other respiratory equipment
      used both in CF centres and for homecare, but little or no evidence of spread
      through aerosols, dental equipment, hands, contaminated disinfectants and water
      supplies. Infection control procedures for reducing the transmission of B.
      cepacia are discussed.

PMID- 8744511
TI  - Survival of Burkholderia cepacia on environmental surfaces.
AB  - Burkholderia (Pseudomonas) cepacia is an important pathogen amongst persons with
      cystic fibrosis (CF), and evidence suggests that transmission of strains within
      CF clinics contributes to pulmonary colonization of some patients. In order to
      optimize preventive strategies, the survival of B. cepacia on various
      environmental surfaces, including cotton cloth, stainless steel, latex and
      polyvinylchloride (PVC) tubing, was investigated. For surface inoculation,
      bacteria were suspended in phosphate buffered saline, sputum from CF patients, or
      sputum from persons without CF. The results demonstrate that amongst the strains
      examined, organisms survived significantly (P < 0.001) longer when suspended in
      sputum from CF patients than in either non-CF sputum or buffered saline.
      Significant (P < 0.001) differences in survival on the various surfaces were
      found; survival was greatest on PVC. Significant (P < 0.001) strain-to-strain
      differences in survival were also demonstrated; patient isolates representing
      predominant CF centre ribotypes survived longest. These data demonstrate that (1)
      B. cepacia can survive for long periods in respiratory droplets on environmental
      surfaces typically found in CF clinics, (2) undefined factors in sputum from
      patients with CF may contribute to survival of B. cepacia, and (3) strain-to
      strain variation in survival time may affect strain transmissibility.

PMID- 8744510
TI  - Blanket use of intranasal mupirocin for outbreak control and long-term
      prophylaxis of endemic methicillin-resistant Staphylococcus aureus in an open
      ward.
AB  - In December 1992, a thoracic ward in a Melbourne teaching hospital experienced an
      increase in patients infected with methicillin-resistant Staphylococcus aureus
      (MRSA). It was decided to attempt to control the outbreak by cohorting positive
      patients (infected and colonized), as well as nurse cohorting, emphasis on
      handwashing, and use of intranasal mupirocin initially three times a day for
      three days, then thrice weekly, for all patients in the ward (with or without
      MRSA). The campaign comprised for phases of 53, 45, 92 and 365 days,
      respectively. Patient and nurse cohorting stopped at the end of phase I. In
      phases I and II, surveillance nose swabs were taken on admission, then twice
      weekly; in phase III, on admission and weekly and in phase IV, on admission until
      the end of 1993. In phases I and II (98 days), only one patient acquired MRSA.
      When the frequency of mupirocin prophylaxis was decreased to once weekly (phase
      III), two patients acquired MRSA in 92 days (no significant difference): thrice
      weekly administration resumed (phase IV), during which there were three
      acquisitions in 365 days. The rates of nose colonization of admissions were 6.4%,
      6.3%, 9.7% and 3.1% in phase I-IV, respectively. Only three patients were treated
      with vancomycin between July 1993 and June 1994 (significantly lower than
      historical rates, P = 0.0086). No mupirocin resistance was seen in MRSA isolates
      from this ward during phases I, II and III. In areas of low-level endemic MRSA,
      the blanket use of thrice-weekly intranasal mupirocin may be effective in
      decreasing serious infections with MRSA, and does not necessarily elicit
      mupirocin resistance.

PMID- 8744512
TI  - Nosocomial acquisition of Escherichia coli by infants delivered in hospitals.
AB  - The delivery of infants in hospitals is desirable for obstetric reasons, but
      exposes the neonates to the microbiological hazards of a maternity unit. When
      neonates are born and cared for in hospital, the Escherichia coli strains that
      colonize the intestine tend to be acquired from the environment or from other
      babies, and are potentially pathogenic. The colonization of the infant with
      maternal flora should be promoted by strict rooming-in of mother and baby, or by
      delivery at home.

PMID- 8744513
TI  - Sporicidal activity of sodium dichloroisocyanurate, peroxygen and glutaraldehyde
      disinfectants against Bacillus subtilis.
AB  - The activity of sodium dichloroisocyanurate (NaDCC), peroxygen and glutaraldehyde
      disinfectants against spores of Bacillus subtilis NCTC 10073 was evaluated using
      suspension tests. The activity of aqueous solutions of NaDCC disinfectants
      increased with the level of available chlorine (av.Cl) but was considerably
      reduced by low levels of blood. Five percent Titan Sanitizer (1200 ppm av.Cl)
      achieved a > 10(5)-fold reduction in spore count (kill) in 3 h in the absence of
      blood but no kill in 3 h with 2% blood present. One percent Presept (3180 ppm
      av.Cl) achieved a > 10(5)-fold kill in 1 h in the absence of blood and in 2 h
      with 2% blood present. One percent Haz-Tab (5750 ppm av.Cl) achieved > 10(5)-fold
      kill in 5 min in the absence of blood and in 30 min with 2% blood present. One
      percent Virkon (peroxygen) achieved a 10(5)-fold kill in 2-3 h in the absence of
      blood but little kill in 3 h with 2% blood present. Nu-Cidex (peracetic acid) was
      rapid in action and tolerant of organic matter. A 24 h old solution achieved a >
      10(5)-fold kill in 5 min with 10% serum present. Cidex Long-Life (glutaraldehyde)
      worked much slower; a 28-day-old solution achieved a > 10(5)-fold kill in 2 h
      with 4% blood present. Neat sporicidin (glutaraldehyde-phenate) was slightly
      superior to Cidex Long-Life but in a 1 in 8 dilution exhibited markedly reduced
      activity; 30-day-old solution achieved a 10(4)-fold kill in 10 h in the absence
      of blood but only a 10(2)-fold kill in 10 h with 2% blood present.

PMID- 8744514
TI  - Dental instrument and device sterilization and disinfection practices.
AB  - Dental instruments and devices require sterilization or high-level disinfection.
      An evaluation of the implementation of such processes was undertaken. Eleven
      thousand questionnaires on methods used to sterilize and disinfect dental
      instruments were sent to dental practices and 1391 (13%) were returned for
      evaluation. Sixty-eight percent of respondents believed they were sterilizing
      their instruments, however, some of the liquid chemical products used were not
      suitable for sterilizing instruments, and 12% of respondents used incorrect
      contact times. Forty-nine percent of respondents did not challenge autoclaves
      with biological spores to check their function at an acceptable frequency. There
      were similar product and timing problems when a high-level liquid chemical
      disinfection was attempted. Although the return sample was small, problems were
      identified that can and should be corrected. This study demonstrates that the
      potential for person-to-person transmission of infectious agents such as the
      human immunodeficiency virus (HIV) and hepatitis B and C viruses via inadequately
      sterilized dental instrument exists depending on the prevalence of HIV in the
      dental practice area.

PMID- 8744515
TI  - Comparison of DNA fingerprinting by PFGE and PCR-RFLP of the coagulase gene to
      distinguish MRSA isolates.
AB  - Staphylococcus aureus isolates were collected from epidemiologically unrelated
      clinical sources in Japan between 1991 and 1993. A total of 40 isolates, five
      each of eight coagulase types, were analysed by polymerase chain reaction (PCR)
      of the coagulase gene, PCR-restriction fragment length polymorphism (RFLP) after
      AluI digestion, and pulsed-field gel electrophoresis (PFGE) of chromosomal DNA
      after SmaI digestion. The efficiency of discrimination among the isolates
      increased in the order of PCR < PCR-RFLP < PFGE, yielding five, 13 and 31
      different types, respectively. To assess the clinical use of these methods, 42
      additional methicillin-resistant S. aureus (MRSA) isolates collected from 27
      inpatients in a hospital were analysed. PFGE and PCR-RFLP were able to
      discriminate 11 and four types, respectively. PFGE analysis detected cross
      infection between four postoperative patients in an intensive-care unit, and in
      six neonates in intensive care. We conclude that of the three methods tested,
      PFGE analysis currently allows the most effective discrimination of MRSA strains.

PMID- 8744516
TI  - Theatre air sampling--once a year is not enough.

PMID- 8744517
TI  - Carriage of Staphylococcus haemolyticus among healthcare workers.

PMID- 8744518
TI  - Clostridium difficile in a healthcare worker.

PMID- 8744519
TI  - Current techniques in mycobacterial detection and speciation.
AB  - Tuberculosis, a health concern so well controlled in recent decades that
      eradication seemed imminent, is once again reaching epidemic proportions
      following the increasing prevalence of AIDS. One important means of curbing this
      resurgence is a robust method that has the capability of identifying and
      speciating mycobacterial infections in a matter of days. Classic biochemical
      techniques, which require 4 to 8 weeks to identify and speciate tuberculosis
      infections, are in the process of being replaced by newer methods, including
      BACTEC, gene probes, nucleic acid amplification, amplification of ribosomal RNA,
      high-performance liquid chromatography, and gas chromatography-mass spectrometry.
      This review is intended to give the reader a synopsis of the current literature
      and research on these methods, including reliability, approximate time required
      for detection and speciation, and clinical utility.

PMID- 8744520
TI  - Fluoride and the skeleton.
AB  - Fluoride has the potential to increase skeletal mass to a greater extent than any
      other pharmacologic agent, yet it has proven difficult to translate this into
      therapeutic benefit for patients with low bone mass in diseases such as
      osteoporosis. This apparent paradox can be explained in part by toxic actions of
      the ion on skeletal mineralization, impairment of the normal processes of bone
      resorption, and fluoride-induced decreases in strength per unit of bone (mass or
      volume). In part, the paradox can be explained by the late stage of osteoporosis
      in most patients enrolled in controlled clinical trials of fluoride, with
      alterations in skeletal microarchitecture beyond which restoration of mechanical
      integrity is not likely. Exposure of calcified tissues to environmental fluoride
      (water supply, dentifrices) also offers paradoxes. The anticaries effects are
      well documented as are the deleterious skeletal effects of endemic fluorosis when
      environmental exposure is too high. More controversial is the effect of seemingly
      nontoxic levels of exposure on the prevalence of osteoporotic fractures of the
      hip. This review attempts to provide a balanced overview of the conflicting
      literature concerning therapeutic and environmental effects of fluoride on the
      skeleton.

PMID- 8744521
TI  - CT manifestations of pulmonary aspergillosis.
AB  - The clinical and radiologic manifestations of pulmonary aspergillosis depend on
      the underlying status of the patients' lung parenchyma and the patients'
      immunologic response to the infecting agent, most commonly Aspergillus fumigatus.
      Thus, many different manifestations of pulmonary aspergillosis have been
      described, with distinct clinical, pathological, and radiological
      characteristics. Aspergillomas (mycetomas) result from Aspergillus colonization
      of preexisting lung cavities. Allergic bronchopulmonary aspergillosis results
      from a hypersensitivity reaction to the fungus in asthmatic patients. Invasive
      aspergillosis occurs in immunocompromised patients and can take one of many
      forms, depending on the degree and etiology of the patients' immunosuppression.
      CT is currently the best imaging modality for the assessment of pulmonary
      parenchymal disease. In the correct clinical setting, the CT findings frequently
      suggest a specific diagnosis. The aim of this review is to discuss and illustrate
      the various CT manifestations of pulmonary aspergillus infection.

PMID- 8744522
TI  - CT of the pulmonary hilum: evaluation with thin-section ultrafast CT.
AB  - The recent progress of CT technology, such as spiral and ultrafast CT, has made
      it possible to obtain contiguous thin-section CT images of the pulmonary hilum
      during rapid injection of contrast material. These CT images consistently provide
      clear images of the pulmonary hilum, including normal peribronchovascular
      interstitium, bronchi, and pulmonary vessels, enabling a more precise and
      detailed evaluation of various pathological conditions than CT previously
      allowed. This article illustrates high-quality CT images in normal and abnormal
      conditions occurring in the pulmonary hilum and discusses the present CT
      diagnosis of various pulmonary hilar diseases.

PMID- 8744523
TI  - Behavior of cells without eye movement sensitivity in the vestibular nuclei
      during combined rotational and translational stimuli.
AB  - A total of 74 neurons that lacked eye movement sensitivity were recorded within
      the confines of the rostral medial and medial lateral vestibular nuclei. Of
      these, 36 had response characteristics that were consistent with combined canal
      and otolith inputs (CAOT neurons), 18 received canal inputs only (CA neurons),
      and 20 had otolith inputs only (OT neurons). Responses were measured during both
      rotational and combined rotational and translational stimuli at 0.5 and 3.0 Hz.
      The otolith signal was found to lag acceleration markedly at both frequencies.
      Indeed, one subset of CAOT neurons had otolith responses that led translational
      velocity by only 12 degrees at 0.5 Hz. All translation-responsive neurons
      decreased their phase lag with respect to acceleration when the stimulus
      frequency was increased and exhibited a large increase in sensitivity. As these
      cells have response dynamics that lie between those seen in otolith afferents and
      those required to drive the motoneurons during the translational VOR, they may
      represent an intermediate stage in the signal processing.

PMID- 8744524
TI  - A model that relates canal-ocular to otolith-ocular responses.
AB  - Rotation about the vertical stimulates primarily the horizontal semicircular
      canals and produces compensatory horizontal nystagmus whose slow component
      velocity response during constant velocity can be approximated as having a simple
      exponential decay time constant, Tvor. Constant velocity yaw rotation about a
      horizontal axis stimulates both the horizontal canals and the otolith organs,
      producing two additional nystagmus components thought to be of otolithic origin:
      a steady component called bias and a periodic component known as modulation. We
      tested a group of 7 human subjects using rotation about each of these axes. We
      found a strong, negative correlation (r = 0.956) between these individuals'
      dominant time constants, Tvor, and the magnitude of their modulation components.
      Canal and otolith signals originate from different parts of the same endorgan and
      travel separately to the vestibular nucleus. The reflexive eye movements in
      response to these inputs are thought to be the result of additional processing by
      the central vestibular and ocular motor systems. Thus, the source of these
      strongly correlated otolith-ocular and canal-ocular reflex components could
      logically be due to common factors affecting peripheral transduction or to a
      subsequent common central processing step. Using anatomical measurements of human
      vestibular end organs, biophysical endorgan models, and models of central
      vestibular processes, we examined the alternatives to determine which was the
      most likely. Correlations were not found between Tvor and the anatomical data or
      between the Tvor and the biophysical model elements. However, modifications of
      the velocity storage integrator of Raphan to incorporate either a highpass filter
      (HPF) or a lowpass filter input for otolith modulation signals allowed for the
      desired strong negative correlation between Tvor and modulation. We argue in
      favor of the HPF configuration because it better explains the tendency for the
      modulation component to increase in amplitude as the modulation frequency is
      increased. In the above mentioned representation of the central processing of
      vestibular afferent inputs, we conclude that the modulation component input to
      the vestibuloocular reflex is within the indirect pathway, but it is "down
      stream" from the velocity storage integrator.

PMID- 8744525
TI  - Benign paroxysmal positional vertigo of the horizontal canal: a form of
      canalolithiasis with variable clinical features.
AB  - Benign paroxysmal positional vertigo of the horizontal semicircular canal (HC
      BPPV) is a well-defined syndrome characterized by direction-changing horizontal
      positional nystagmus. We report the clinical features of 5 patients who
      illustrate the possible variables of the syndrome. In most cases, nystagmus is
      geotropic and more intense when the pathological ear is lowermost; less often the
      syndrome presents with apogeotropic nystagmus that is more intense when the
      affected ear is uppermost. The nystagmus pattern may vary in time in the same
      patient, changing from apogeotropic to geotropic even in observations at short
      intervals. In some patients, the features indicate involvement of more than one
      canal, either simultaneously or in succession. It is sustained that the clinical
      findings can be explained by movement of endolymph caused by displacement of
      otoconia in the semicircular canals and that variants are due to different
      positions of the otoconia within the canals.

PMID- 8744526
TI  - The recovery of static vestibular function following peripheral vestibular
      lesions in mammals: the intrinsic mechanism hypothesis.
AB  - This theoretical paper describes the "intrinsic mechanism hypothesis," a new
      hypothesis of vestibular compensation, the behavioral recovery that follows
      unilateral deafferentation of the vestibular labyrinth (UVD). The most salient
      characteristic of vestibular compensation is the decrease in the severity of the
      static ocular motor and postural symptoms that follow UVD, associated with a
      recovery of resting activity in the ipsilateral vestibular nucleus complex (VNC).
      The speed of static compensation in some mammalian species (for example, cat) has
      suggested that reactive synaptogenesis is an unlikely explanation because it is
      too slow. Other, more rapid mechanisms, such as denervation supersensitivity,
      receptor-up-regulation, or increased neurotransmitter release, were reasonable
      possibilities. However, to date, each study that has addressed these
      possibilities has failed to find any change that could account for the recovery
      of VNC resting activity. The search for such "substitutive" mechanisms was based
      on the hypothesis that something other than the VNC neurons themselves would have
      to "replace" the missing resting activity that the ipsilateral vestibular nerve
      normally provides. However, brainstem slice studies demonstrate that, at least in
      vitro, VNC neurons do not need the vestibular nerve in order to generate resting
      activity. On the basis of these and other considerations, we suggest that
      following a brief calcium-induced diaschisis, VNC neurons ipsilateral to the UVD
      reactivate the intrinsic membrane properties that normally contribute to their
      resting activity in vivo, and that this recovery of resting activity accounts for
      static vestibular compensation.

PMID- 8744527
TI  - Distribution of choline acetyltransferase mRNA in the efferent vestibular neurons
      of the chinchilla.
AB  - The distribution of choline acetyltransferase messenger RNA (mRNA) among efferent
      vestibular neurons in the chinchilla was investigated. mRNA coding for choline
      acetyltransferase, the enzyme that synthesizes acetylcholine, was used as a
      marker for the cholinergic system. In order to retrogradely label the efferent
      vestibular neurons, Fluoro-gold was injected through the oval window into the
      inner ear of anesthetized young male chinchillas (6 to 12 months old). The
      animals were anesthetized and perfused through the heart 2 days post injection
      with 4% paraformaldehyde in phosphate buffer. Retrogradely labeled efferent
      vestibular neurons were mapped in brainstem sections prior to processing for in
      situ hybridization histochemistry using radiolabeled ribonucleic acid probes
      complementary to the 3' end of the choline acetyltransferase mRNA. At the levels
      of the ascending facial nerve and the genu of the facial nerve, we found that
      approximately 90% of the Fluoro-gold labeled cells in group E1 contained choline
      acetyltransferase mRNA. All of the group E2 cells that were labeled with Fluoro
      gold were found to be cholinergic (contain choline acetyltransferase mRNA).
      Finally, 60% of the Fluoro-gold-labeled cells in the caudal pontine reticular
      nucleus contained choline acetyltransferase mRNA.

PMID- 8744528
TI  - Vertical and horizontal eye displacement during static pitch and roll postures.
AB  - The positions of both eyes were measured objectively in the dark following "look
      straight ahead" instructions for 16 subjects at 27 combinations of static pitch
      and roll postures over 360 degrees of space, using an infrared video technique.
      Shifts in vertical version, or the doll reflex, varied sinusoidally with pitch
      and roll angle. At 0 degree roll, the average response has a peak-to-trough
      amplitude of 9.28 degrees and is symmetric about a downward eye position of 4.63
      degrees. The proposed Dual Otolith Model (DOM), based on a combination of
      utricular and saccular inputs, provided excellent fits to the present data (R2 =
      0.876) and to the data of previous studies (R2 = 0.916 to 0.994). Deviations in
      horizontal version varied sinusoidally with roll angle, with no significant
      effect of pitch angle. In general, clockwise (right-ear-down) rolls produced
      rightward eye movements, and counterclockwise (left-ear-down) rolls produced
      leftward eye movements. The average versions were symmetric about a leftward eye
      position of 1.14 degrees, with a peak-to-trough amplitude of 3.76 degrees. The
      data were well represented by the proposed Horizontal Version Model (HVM; R2 =
      0.796), which depended only on utricular input.

PMID- 8744529
TI  - Vestibular bibliography.

PMID- 8744531
TI  - Occupational renal diseases.
AB  - There is no doubt that particular occupational exposures may induce acute renal
      effects. The role of occupational exposure in the development or progression of
      chronic renal failure, however, is still not clear. Recent epidemiological
      studies point towards a contributive role of particular occupational exposures in
      the progression of renal disease. Furthermore, some observations in the 1994-1995
      literature suggest a primary or secondary role, or both, of new substances such
      as silicon-containing compounds in the development of anti-neutrophil cytoplasmic
      antibody-positive rapidly progressive glomerulonephritis and Wegener's
      granulomatosis. Finally, studies suggesting a particular sensitivity of the
      diabetic kidney towards the damaging effects of certain occupational exposures
      deserve confirmation.

PMID- 8744530
TI  - Ischemia, injury, and renal allograft rejection.

PMID- 8744532
TI  - Drugs of abuse and renal disease.
AB  - The complications of drug abuse encompass a spectrum of glomerular, interstitial,
      and vascular diseases. They comprise the heroin-associated nephropathy seen in
      African-American intravenous drug addicts, which, however, has given way in the
      1990s to HIV-associated nephropathy. Infections with methicillin-resistant
      Staphylococcus aureus may cause acute glomerulonephritis by releasing bacterial
      superantigens. Hepatitis C has supplanted hepatitis B and may give rise to
      membranoproliferative glomerulonephritis and cryoglobulinemia. Addicts who inject
      drugs subcutaneously ('skin popping') may develop amyloidosis. Cocaine causes
      rhabdomyolysis, severe hypertension, occasionally renal failure in the absence of
      rhabdomyolysis, and may hasten progression to uremia in patients with underlying
      renal insufficiency. 'Ecstasy', an amphetamine-like recreational drug, has caused
      acute renal failure, electrolyte disturbances, and malignant hypertension. In
      Belgium and some other European countries, women taking Chinese herbs in a
      slimming regimen have developed a severe and irreversible interstitial fibrosis
      that is assuming epidemic proportions.

PMID- 8744533
TI  - Contrast media-associated nephrotoxicity.
AB  - Contrast media-associated nephrotoxicity continues to be a common cause of acute
      renal failure. We review recent developments in our understanding of the
      pathogenesis of this complication, focusing on the role of vasoactive substances
      which include adenosine, endothelium-derived relaxing factor, and endothelin. An
      overview of clinical features is presented with an emphasis on the value of low
      osmolar contrast media in azotemic patients. Prophylactic strategies are reviewed
      focusing on saline hydration alone, vasoactive pharmacological agents,
      theophylline, 'prophylactic hemodialysis', and possible differences in how these
      maneuvers affect diabetic and non-diabetic azotemic patients are discussed.

PMID- 8744534
TI  - IgA-associated renal diseases.
AB  - IgA nephropathy and Schonlein-Henoch purpura nephritis are common renal diseases.
      Recent studies have provided new insights into the factors that contribute to the
      initiation and progression of renal injury. Approaches to therapy, although still
      limited and largely empirical, show some encouraging results.

PMID- 8744535
TI  - Hyperlipidemia and its management in renal disease.
AB  - Dyslipidemia is common in patients with renal disease, may contribute to the high
      incidence of cardiovascular disease, and may play a role in progressive renal
      injury. Recent studies have shown that newer antilipemic agents appear to be safe
      and effective in patients with renal disease. This should make it possible to
      conduct large, controlled clinical trials examining the effect of lipid-lowering
      strategies on cardiovascular disease, and on renal disease progression.

PMID- 8744536
TI  - Renal disease in pregnancy.
AB  - The incidence of acute renal failure in South Africa has been reduced and is a
      reflection of improved obstetric care. A report of eclampsia in the UK suggests
      that eclampsia with its attendant risk of acute renal failure may never be
      eliminated completely. There has been progress in understanding the changes in
      endothelial cell metabolism and pre-eclampsia but there has been limited success
      in improving treatment. The development of hypertension or pre-eclampsia during
      pregnancy may predict the development of hypertension, but it rarely indicates
      underlying renal disease. It appears that pregnancy does not adversely affect the
      course of renal disease if renal function is normal at conception, but it may
      hasten the decline in renal function in women who have impaired renal function at
      conception. The frequency of complication both for mother and for child remain
      high in such pregnancies.

PMID- 8744537
TI  - Diagnosis and management of renal infections.
AB  - The interest of nephrologists in renal infections has waxed and waned over past
      decades, despite the fact that acute pyelonephritis is the most common of all
      renal diseases. A host of new antibiotics highly effective against urinary
      pathogens probably contributed to the notion that renal infection had disappeared
      from te field of renal medicine. In fact, a flurry of recent publications sheds
      new light on the pathophysiology and the immunology of this inflammation of renal
      tissue, its diagnosis by means of ingenious imaging techniques and the risk it
      carries of renal scarring.

PMID- 8744538
TI  - Antihypertensive therapy in the era of evidence based medical practice: what to
      do until the facts are in.

PMID- 8744539
TI  - Recent advances in the molecular genetics of hypertension.
AB  - The application of genetic strategies to studies of the pathogenesis of
      hypertension has proceeded on multiple fronts in the past year and has provided
      new insight into disease pathogenesis. Studies of monogenic forms of hypertension
      have led to the identification of genes causing Liddle's syndrome and the
      syndrome of apparent mineralocorticoid excess, while studies of essential
      hypertension have examined the potential roles of a number of candidate genes.
      Animal models have been exploited, both by mapping of naturally occurring
      mutations that alter blood pressure and by physiologic analysis of animals
      harboring specific engineered mutations.

PMID- 8744540
TI  - Dietary salt and hypertension.
AB  - Sodium restriction is the most commonly used lifestyle modification for control
      of hypertension. Nevertheless, there is no consensus on the relative importance
      of salt in the development of hypertension, nor is the physiological mechanism(s)
      responsible for salt-induced elevations of blood pressure clearly understood.
      This review focuses on new research developments in this area.

PMID- 8744541
TI  - Natriuretic peptides and hypertension.
AB  - Natriuretic peptides are produced in the brain, heart and vasculature, and cause
      vasodilation, sodium excretion, and diuresis. Recent advances indicate that they
      play important roles in blood-pressure homeostasis, both in normal and in
      pathophysiological conditions. Although therapeutic interventions which elevate
      plasma natriuretic peptide levels do not have great antihypertensive efficacy,
      animal studies suggest that they may be useful in combination treatment
      strategies.

PMID- 8744542
TI  - Nitric oxide and hypertension in 1995.
AB  - Insight is rapidly developing into the physiological production and function of
      nitric oxide. This small molecule has several physiological actions that oppose
      the pathogenesis of hypertension. Originating in the endothelium, it causes
      vascular smooth muscle relaxation, lowering blood pressure. In the central
      nervous system nitric oxide tonically depresses activity of the sympathetic
      nervous system, and in the kidney it regulates renin release and causes
      natriuresis. Nitric oxide may also contribute to the protective action of
      oestrogen.

PMID- 8744543
TI  - Sexual dimorphism of hypertension.
AB  - A sexually dimorphic pattern of blood pressure, in which the male develops higher
      blood pressure than the age-matched female, has been observed both in human
      subjects and in laboratory animals. The mechanism(s) of this sexual dimorphism of
      blood pressure are not completely understood. This review summarizes sex
      differences in the epidemiology of hypertension in humans, the role of gonadal
      steroid hormones in the regulation of blood pressure of normotensive and
      hypertensive laboratory animals, and new insights into the molecular basis of the
      sexual dimorphism of hypertension and hypertensive vascular disease.

PMID- 8744544
TI  - Cardiac hypertrophy and failure in hypertension.
AB  - Left ventricular hypertrophy is both a major adaptive response to chronic
      pressure overload and an important risk factor in patients with hypertension. It
      is now well appreciated that structural changes in the myocardium are mediated
      not only by the mechanical stress of pressure overload but also by various
      neurohormonal substances that exert trophic effects on myocytes and non-myocytes
      in the heart. Both earlier recognition and improved understanding of cardiac
      hypertrophy may lead to more effective therapeutic strategies for hypertension.
      This review focuses on the underlying mechanisms in hypertensive heart disease
      that lead to heart failure.

PMID- 8744545
TI  - White coat hypertension.
AB  - Several recent studies of white coat hypertension have confirmed that it occurs
      in 20% or more of the hypertensive population. White coat hypertension appears to
      be a low-risk condition because it is associated with little or no organ damage,
      and is not usually associated with the metabolic abnormalities characteristic of
      sustained hypertension, such as high plasma lipid levels. Thus the cutoff point
      used to define white coat hypertension is increasingly being used as a treatment
      threshold. An alternative approach for defining treatment thresholds has been the
      study of ambulatory blood pressure in normotensive populations, taking the 95th
      percentile as the upper limit of normal. This approach yields unacceptably high
      cutoff points. Studies of the white coat effect, defined as the difference
      between clinic and ambulatory pressure, have shown that it is more pronounced in
      patients with more severe hypertension, and that it does not correlate with
      target organ damage. Drug treatment of white coat hypertension often results in a
      reduction of clinic pressure more than of ambulatory pressure, but the white coat
      effect is still seen in treated patients. One recently published study indicates
      that the prognosis of white coat hypertensive patients in benign.

PMID- 8744547
TI  - Pathophysiology of hypertension.

PMID- 8744546
TI  - Clinical nephrology.

PMID- 8744548
TI  - Protection against oral challenge three months after i.v. immunization of BALB/c
      mice with live Aro Salmonella typhimurium and Salmonella enteritidis vaccines is
      serotype (species)-dependent and only partially determined by the main LPS O
      antigen.
AB  - The role of the main LPS O antigen in the specificity of protection as mediated
      by systemic mechanisms following immunization with live attenuated Aro Salmonella
      vaccines was studied in mice. Innately Salmonella-susceptible (Itys) BALB/c mice
      were immunized intravenously with a single dose of either Salmonella typhimurium
      SL3261 aroA (LPS O4,5,12) or Salmonella enteritidis Se795aroA (LPS O1,9,12), and
      challenged orally 2-3 months later with either S. typhimurium C5 or S.
      enteritidis Thirsk. Nearly isogenic transductants of the two challenge strains
      expressing either their own LPS or that of the other serotype (S. typhimurium C5
      O4 or O9, and S. enteritidis Thirsk O9 or O4) were also used. Both vaccines
      conferred similar high protection against the virulent strain of the homologous
      serotype expressing its own LPS. There was no protection against the heterologous
      serotype expressing its own LPS. However, when vaccinated mice were challenged
      with either the same serotype as the vaccine but expressing the heterologous LPS,
      or with the heterologous serotype expressing the LPS of the vaccine, protection
      was always lower than protection against the fully homologous serotype. Anti
      smooth LPS antibodies showed higher titres against the homologous LPS, but with
      significant crossreactivity with the heterologous LPS. Antibodies to O-rough S.
      typhimurium and S. enteritidis LPS were present following immunization with
      either of the two vaccine strains. The LPS alone cannot fully account for the
      specificity of protection in this model; other (protein) antigens may be
      responsible. It remains to be seen whether there is a T-cell mediated component
      to the specificity of protection conferred by live Salmonella vaccines.

PMID- 8744549
TI  - Mucosal immunogenicity of the Escherichia coli heat-labile enterotoxin: role of
      the A subunit.
AB  - The Escherichia coli heat-labile enterotoxin (LT) is a potent mucosal immunogen,
      inducing high secretory as well as systemic antibody responses upon oral or
      intranasal (i.n.) administration. In addition, LT has the capacity to act as an
      adjuvant in antibody responses against coadministered other antigens. To
      investigate the role of the individual subunits of LT in the mucosal
      immunogenicity and adjuvanticity of LT, the LT holotoxin and the non-toxic B
      subunit (LTB) were cloned separately and purified from overproducing E. coli
      cultures. Mice were immunized i.n. with the recombinant LT, LTB and combinations
      of the two and the induction of LTB-specific serum IgG and IgA as well as mucosal
      S-IgA was monitored. Intranasal administration of 2 micrograms LTB by itself
      induced a moderate systemic and a low mucosal antibody response, the latter being
      restricted to the site of immunization. However, addition of a trace amount (50
      ng) of LT holotoxin to LTB strongly stimulated both serum antibody and mucosal S
      IgA responses to LTB: the antibody levels induced by 2 micrograms LTB
      supplemented with 50 ng LT were similar to those seen after immunization with 2.9
      micrograms of the LT holotoxin alone (representing an amount of 2 micrograms
      LTB). Furthermore, immunization with LT-supplemented LTB or with LT holotoxin
      alone, but not immunization with LTB alone, induced an S-IgA response in distant
      mucosal tissues including the lung, intestine and the urogenital system. Nicking
      of the LTA chain with trypsin did not enhance the immunogenicity of LT. These
      results indicate that, although the LTA chain plays an important role in the
      mucosal immunogenicity of LT including priming of the common mucosal immune
      system, extremely low amounts of the LT holotoxin suffice for the induction of
      high antibody responses to LTB, the trace LT and LTB acting in a synergistic
      fashion.

PMID- 8744550
TI  - Immune response to a booster dose of enhanced potency inactivated polio vaccine
      administered in association with HBV vaccine in adolescents.
AB  - The immunogenicity and reactogenicity of a booster dose of enhanced potency
      inactivated polio vaccine (EIPV) were evaluated in 492 healthy 12 year old
      adolescents. The booster was administered at the same time as the HBV vaccine
      compulsory in Italy at this age. Blood samples and questionnaires on
      reactogenicity were collected over 9 months. Analysis of pre-vaccination immunity
      showed that 97.4% of the subjects were protected against all polio types, 1.9%
      were negative for two polio types and 0.6% for one. After vaccination 98.4% of
      the vaccinees showed a significant increase ( > or = 4 times) of antibody titre;
      the geometric mean titres (GMT) were markedly higher than before vaccination,
      particularly for poliovirus type 3. The polio booster dose did not affect HBV
      vaccination. An anti-HBs response > 10 mIU ml-1. (GMT = 2951 mIU ml-1) was
      observed in 781 (98.6%) of 792 vaccinees (492 given EIPV+HBV and 300 given only
      HBV) 9 months later. Only mild local and rare general reactions were noted for
      both the vaccines studied. These data confirm the suitability and efficacy of an
      EIPV booster dose and HBV vaccination in adolescents.

PMID- 8744551
TI  - Evaluation of the safety of two attenuated oral rabies vaccines, SAG1 and SAG2,
      in six Arctic mammals.
AB  - The safety of two attenuated oral rabies vaccines was evaluated in mink and in
      five species of rodents which occur in the Arctic. A 0.03 ml sample of liquid
      vaccine was installed directly into the mouth of voles and lemmings and 0.1 ml
      into the mouth of Arctic ground squirrels and mink. Animals were euthanized at 36
      and 46 days postexposure; brain tissue was analyzed by FAT and serum by RFFIT. No
      rabies deaths occurred in 47 animals tested. Four animals representing three
      rodent species seroconverted, the highest titer being 0.5 IU ml-1. The absence of
      rabies virus in brain tissue indicates the safety of these vaccines in these
      species. The replacement of arginine with glutamic acid at position 333 reduces
      the pathogenicity of these vaccines, thereby presumably preventing the
      deleterious effect of viral entry into CNS neurons.

PMID- 8744552
TI  - Improvement of the Brucella abortus B19 vaccine by its preparation in a glycerol
      based medium.
AB  - The Brucella abortus B19 vaccine strain differs from other Brucella strains in
      its sensitivity to erythritol. However, erythritol tolerant (Eri(t)) mutants
      arise from sensitive cultures of B19 at high rate, and may cause persistence
      and/or abortion when the vaccine is inoculated on adult cattle. Twelve different
      batches of B19 have been examined for the presence of Eri(t) mutants. All
      contained Eri(t) variants at a proportion ranging from 10(-4) to 10(-6). In order
      to eliminate these mutants from the vaccine cultures, we have developed a minimal
      medium with glycerol as the sole carbon source, named MMG30. Growth of the
      parental strain B19 (erythritol sensitive) in this medium was fairly good
      compared with the growth of its Eri(t) derivatives. Culture of the 12 different
      batches of B19 in liquid MMG30 produced up to a thousandfold decrease in the
      proportion of Eri(t) mutants present in the vaccine cultures. Use of this medium
      to grow B19 could represent an easy and considerable improvement of the vaccine,
      by the reduction of the presence of potentially dangerous Eri(t) mutants.

PMID- 8744553
TI  - Asymmetric deletion of the junction between the short unique region and the
      inverted repeat does not affect viral growth in culture and vaccine-induced
      immunity against Marek's disease.
AB  - To construct an effective recombinant Marek's disease virus type 1 (MDV1), we
      localized a stable insertion site for expression of the Escherichia coli lacZ
      gene near or within the short inverted repeats of MDV1 strain K554 DNA. A stable
      recombinant MDV1 was obtained by deleting the junction region between the short
      unique sequence (Us) and the internal short inverted repeat (IRs). The
      recombinant MDV1 replicated in cultured cells as well as the parental viral DNA.
      Antibodies against both MDV1 antigen and beta-galactosidase encoded by the lacZ
      gene were detected in the sera of chickens immunized with the virus, and
      persisted for at least 16 weeks. Moreover, the recombinant virus conferred
      protection upon chickens against a challenge with virulent MDV1. These results
      demonstrated that the Us-IRs junction region is an effective site for the
      insertion of foreign genes from which to construct a polyvalent live vaccine for
      poultry. Analysis of the Us-IRs junction region which was deleted from the
      parental MDV1 indicated that there is a tandem direct repeat of a 220-bp exists
      within the short internal and terminal inverted repeats of avirulent MDV1 K554
      strain DNA. The 220-bp sequence was well conserved among DNAs from various
      strains. The number of the repeat units may differ between the IRs and TRs or
      among various MDV1 strain DNAs.

PMID- 8744554
TI  - Evaluation of subunit vaccines against feline immunodeficiency virus infection.
AB  - Subunit vaccines prepared against feline immunodeficiency virus (FIV) infection
      were evaluated in two trials. First, cats were immunized with bacterial
      expression products of an envelope fragment that contained the V3 neutralization
      domain of the FIV surface protein fused to either galactokinase (K-SU3) or
      glutathione-S-transferase (G-SU3). Quantitative and qualitative differences in
      the humoral immune response were observed with three adjuvants of which Quil A
      was the best in terms of total and virus neutralizing antibody. Notwithstanding
      the responses induced, 19 of 20 immunized cats did not resist challenge and
      became infected. To determine whether priming with a live viral vector would
      confer protection, cats were inoculated oronasally and subcutaneously with a
      feline herpesvirus (FHV) mutant expressing the FIV env gene; two booster
      immunizations followed using the K-SU3 product in either Quil A or a mineral oill
      Al(OH)3 adjuvant. FIV-specific antibody responses were only weak, and the
      vaccinates did not withstand challenge with a low dose of homologous virus.

PMID- 8744555
TI  - Pertussis toxin enhanced IgG1 and IgE responses to primary tetanus immunization
      are mediated by interleukin-4 and persist during secondary responses to tetanus
      alone.
AB  - Pertussis toxin (Ptx), the major toxin product of Bordetella pertussis, has
      potent immunologic effect including adjuvant effects on antibody responses and
      sensitization for anaphylaxis. In order to further define the effect of Ptx on
      the class and subclass of murine antibody response, we measured total and antigen
      specific IgG subclasses and IgE in Balb/c mice after primary and secondary
      immunization with tetanus toxoid (TT). Low doses of Ptx (100 ng) given
      intravenously at the time of primary immunization increased primary IgG1 and IgE
      anti-TT antibodies as well as total IgG1 and IgE concentrations compared to
      controls. The increase in IgG1 subclass and IgE response when Ptx was present
      during primary immunization was even more pronounced after secondary immunization
      with TT alone 3 weeks or 3 months later. Similar effects were noted after
      diphtheria toxoid immunization in the presence of Ptx. Administration of the anti
      IL-4 monoclonal antibody (11B11) suppressed the enhanced total and TT-specific
      IgE responses but not the enhanced IgG1 responses. The presence of low
      concentrations of Ptx during primary immunization primes for induction of IL-4
      producing T-cell help which enhances IgGI and IgE responses to the primary
      exposure as well as to subsequent exposures of the antigen in the absence of Ptx.
      This phenomenon may have significance for the adjuvant activity of vaccines
      containing Ptx as well as for the immune response to natural pertussis.

PMID- 8744556
TI  - Treatment of aluminium hydroxide adjuvant to optimize the adsorption of basic
      proteins.
AB  - Aluminium hydroxide adjuvant has an isoelectric point (i.e.p.) of ca 11 and is a
      good adsorbent for acidic proteins due to the contribution of electrostatic
      attractive forces. However, electrostatic repulsive forces reduce its ability to
      adsorb basic proteins. Pretreatment of aluminium hydroxide adjuvant with
      carefully selected concentrations of phosphate anion reduces the positive surface
      charge which exists at pH 7.4. Treatment with higher concentrations of phosphate
      anion produces a negative surface charge. The adsorption of lysozyme (i.e.p =
      11.1) was found to be directly related to the concentration of phosphate anion
      used to pretreat the aluminium hydroxide adjuvant.

PMID- 8744557
TI  - The influence of a recombinant-HBsAg vaccine on the repertoire of transcribed T
      cell receptor beta chain variable region genes in peripheral blood in humans.
AB  - The purpose of this study was to determine whether in vivo changes in the
      repertoire of Tcr beta chain variable region (V beta) genes could be detected in
      peripheral blood mononuclear cells after immunization of humans with recombinant
      hepatitis B virus envelope protein (rHBsAg). We measured the percentage of Tcr
      RNA transcripts carrying each of 20 V beta genes in human PBMC before and after
      immunization with rHBsAg in Polynesians (8 non-immunized controls, 26 immunized
      subjects) and Europeans (9 non-immunized controls, 11 immunized subjects). The
      per cent of RNA transcripts containing V beta 7.4 family genes was increased in
      immunized vs control Polynesian (+ 1.6 +/- 0.5%) vs -1.1 +/- 0.3%, P = 0.0002)
      and European (+1.6 +/- 0.6% vs -0.1 +/- 0.5%, P = 0.05) subjects at 48 h and 28 h
      post-immunization, respectively. No changes in V beta repertoire were found after
      48 h in either race. Thus, there is a transient increase in frequency of T cells
      with Tcr containing V beta 7.4 family genes within 48 h of an immunization
      containing rHBsAg in humans. There are a number of explanations for this finding,
      including the possibility that V beta 7.4 gene family products may be
      preferentially involved in the primary immune response to HBsAg.

PMID- 8744558
TI  - Antigenic determinants at the carboxy terminus of chicken egg white riboflavin
      carrier protein (RCP): epitope mapping and antibody-mediated pregnancy
      curtailment in rodents.
AB  - The epitopic core sequences recognized by three monoclonal antibodies raised to
      chicken riboflavin carrier protein (RCP) were mapped to the C-terminal tail-end
      of the protein using the pepscan method. A 21-residue synthetic peptide
      corresponding to residues 200-219 of the protein and comprising the regions
      corresponding to the antibodies was synthesized. Administration of polyclonal
      antibodies specific to this peptide led to termination of early pregnancy in
      mice. Also, active immunization of rats with the peptide-purified protein
      derivative conjugate inhibited establishment of pregnancy. These results
      demonstrate the functional importance of the C-terminal 200-219 region of chicken
      RCP.

PMID- 8744559
TI  - Global DTP manufacturing capacity and capability. Status report: January 1995.
AB  - A recently completed survey of 63 manufacturers of diphtheria-tetanus-pertussis
      (DTP) vaccine and its components in 42 countries shows that there is potentially
      a large excess installed capacity for DTP production. However, many manufacturers
      are not producing to capacity, and demand and supply for this vaccine are not
      matched in individual countries. About half of all countries producing DTP
      vaccine and its components do not have fully functional national control systems,
      and some countries are performing none of the critical functions for an effective
      control of quality. Thus, potential for export of excess capacity is limited. The
      data collected indicate much homogeneity in the preparation of diphtheria and
      tetanus toxoids. Nearly all manufacturers use the same seeds and similar
      purification methods, but there is variability in whether purification is done
      before or after conversion of toxin to toxoid. About 10% of all manufacturers do
      not meet WHO-defined standards of purity for these toxoids. There is much more
      heterogeneity in the pertussis seed strains and the methods of purification used.
      The formulation of DTP vaccine differs considerably among producers. Potency
      testing is not being done by the WHO-recommended method by about 50% of
      manufacturers on lots of diphtheria and tetanus toxoids for release. Testing of
      irreversibility of conversion of toxin to toxoid, a WHO-specified safety test, is
      also not being done on each lot of diphtheria toxoid by 15% of manufacturers
      surveyed nor on each lot of tetanus toxoid vaccine by 30% of manufacturers
      surveyed. Access to technology to develop new DTP-based combination vaccines will
      be delayed if these manufacturers cannot ensure consistent high quality vaccine
      for their target populations. The results and conclusions suggest areas for
      future activities to strengthen the supply and quality of DTP and DTP-based
      combination vaccines.

PMID- 8744560
TI  - Enhancement of antigen presentation of influenza virus hemagglutinin by the
      natural human anti-Gal antibody.
AB  - Immunogenicity of inactivated virus or subviral vaccines may be enhanced by
      complexing with an IgG antibody. Such antibody would increase the uptake,
      processing and presentation of the vaccine's antigens by antigen presenting cells
      (APC), via the adhesion of the antibody-vaccine complex to Fc-receptors on
      macrophages and other APC. A natural antibody in humans, which may be generally
      exploited for this purpose, is the natural anti-Gal antibody. This antibody is
      ubiquitously produced as 1% of circulating IgG in humans and Old World primates,
      and it interacts specifically with the carbohydrate epitope Gal alpha 1-3 Gal
      beta 1-4 GlcNAc-R (termed the alpha-galactosyl epitope). This epitope is
      synthesized in large amounts in cells of nonprimate mammals and New World monkeys
      by the glycosylation enzyme alpha 1,3 galactosyltransferase. Here we describe in
      vitro studies on the ability of anti-Gal to bind to alpha-galactosyl epitopes on
      influenza virus propagated in mammalian cells, and to enhance presentation by APC
      of viral hemagglutinin antigenic determinants to specific helper T cell clones.
      The various approaches for achieving alpha-galactosyl epitope expression on
      virion and subviral vaccines are discussed.

PMID- 8744561
TI  - Testing of a dengue 2 live-attenuated vaccine (strain 16681 PDK 53) in ten
      American volunteers.
AB  - A live-attenuated dengue 2 vaccine (strain 16681 PDK 53) developed at Mahidol
      University, Thailand was evaluated for safety and immunogenicity by administering
      10(4) p.f.u. subcutaneously to ten flavivirus non-immune American volunteers. The
      vaccine was safe; there were no serious adverse reactions. Eight recipients
      experienced no or mild side effects. One recipient reported headaches on 7
      separate days. One volunteer, who had a fracture of the humerus 1 day after
      vaccination requiring surgical repair, experienced generalized malaise with fever
      (maximum temperature = 38.9 degrees C), headache, eye pain and myalgia lasting
      less than 24 h. The vaccine was highly immunogenic; all recipients developed
      neutralizing antibody that persisted for two years.

PMID- 8744562
TI  - Long-term duration of detectable neutralizing antibodies after administration of
      live-attenuated VEE vaccine and following booster vaccination with inactivated
      VEE vaccine.
AB  - The US Army successfully developed a live-attenuated Venezuelan Equine
      Encephalitis (VEE) vaccine, TC-83, in 1961, and subsequently developed a formalin
      inactivated vaccine, C-84, in 1974. Initial evaluation of both vaccines was
      promising, but no long-term safety and immunogenicity data have been reported.
      This study is the first analysis of the long-term safety and immunogenicity of TC
      83 and C-84. From January 1976 to December 1990, 821 laboratory workers at the
      USAMRIID were vaccinated with a single 0.5 ml subcutaneous (s.c.) dose of TC-83;
      128 were boosted with a single 0.5 ml s.c. dose of C-84. Eighty-two per cent of
      vaccinees responded to TC-83 with an 80% plaque reduction neutralization titer
      (PRNT80) of > or = 1:20. Minor side-effects were noted in 23% of vaccinees. No
      long-term sequelae were recorded. Kaplan-Meier analysis showed a 60% probability
      of vaccinees maintaining a PRNT80 of > or = 1:20 for 5.5-8 years. C-84 was given
      to two groups: 76 initial nonresponders to TC-83, Group A, and 52 initial
      responders to TC-83 whose PRNT80 became < 1:20 over time, Group B. C-84
      successfully boosted 76% of Group A and 100% of Group B to a PRNT80 > or = 1:20
      Kaplan-Meier analysis showed 100% probability of Group B members maintaining a
      titer of > or = 1:20 for the duration of follow-up, which, in some cases,
      exceeded 10 years; while Group A had only a 60% probability of maintaining a
      titer for 1-2 years. Only minor local reactions to C-84 were noted in 6.3% of
      vaccinees. We conclude that, although TC-83 is reactogenic, when administered as
      the primary vaccine and C-84 is administered as a boost, these vaccines provide
      good long-term immunity and are safe in humans. However, a single dose vaccine
      that is more immunogenic and less reactogenic is needed.

PMID- 8744563
TI  - Induction of homologous virus neutralizing antibodies in guinea-pigs immunized
      with two human immunodeficiency virus type 1 glycoprotein gp120-iscom
      preparations. A comparison with other adjuvant systems.
AB  - The immunogenicity in guinea-pigs of the human immunodeficiency virus type 1
      envelope glycoprotein gp120 in immune stimulating complex (iscom) was compared to
      that of gp120 adjuvanted with QuilA-matrix (iscom without attached antigen),
      aluminium hydroxide (alum) and the Ribi adjuvant system. Gp120 was either
      incorporated into iscoms by covalent conjugation (iscom(c)) or by acid treatment
      of gp120 (iscom(a) and both these preparations induced high ELISA antibody titres
      to gp120. Virus neutralizing (VN) antibodies were most frequently induced by
      gp120 in iscom(c), iscom(a) or in alum and correlated to high titres to the V3
      region of gp120. Further, antibodies induced by gp120-iscom(c) most efficiently
      inhibited binding of a VN monoclonal antibody GP13 to the CD4 binding region of
      gp120 whereas gp120-iscom(a) induced the highest mean titre of antibodies
      blocking the binding of [125I]gp120 to CD4. These results suggest that the gp120
      iscom preparations efficiently induced high levels of gp120 specific antibodies
      and that the adjuvant formulation of gp120 affect the specificity and functional
      properties of elicited antibodies.

PMID- 8744564
TI  - HIV-1 candidate vaccines can induce antibodies which share specificity with human
      monoclonal antibodies capable of neutralizing primary isolates.

PMID- 8744565
TI  - Quantitative determination of immune response against hepatitis A virus capsids
      after natural infection.

PMID- 8744566
TI  - BOOMSLANG: a program for combinatorial structure generation.
AB  - An approach to exploiting pharmacophore models is described. Structures are
      assembled combinatorially from user-defined fragments and flexibly overlaid into
      the reference frame of the pharmacophore using distance geometry and molecular
      mechanics. The match with the pharmacophore is quantified by conformational
      energy and volume of overlap.

PMID- 8744567
TI  - Finding and visualizing nucleic acid base stacking.
AB  - Base stacking is one of the primary factors stabilizing nucleic acid structure.
      Yet, methods for locating stacking interactions in DNA and RNA are rare and
      methods for displaying stacking are rarer still. We present here simple,
      automated procedures to search nucleic acid molecules for base-base and base
      oxygen stacking and to display these interactions graphically in a manner that
      readily conveys both the location and the quality of the interaction. The method
      makes no a priori assumptions about relative base positions when searching for
      stacking, nor does it rely on empirical energy functions. This is a distinct
      advantage for two reasons. First, the relative contributions of the forces
      stabilizing stacked bases are unknown. Second, the electrostatic and hydrophobic
      components of base stacking are both poorly defined by existing potential energy
      functions.

PMID- 8744568
TI  - Neural networks as a tool for compact representation of ab initio molecular
      potential energy surfaces.
AB  - Ab initio quantum chemical calculations of molecular properties such as, e.g.,
      torsional potential energies, require massive computational effort even for
      moderately sized molecules, if basis sets with a reasonable quality are employed.
      Using ab initio data on conformational properties of the cofactor (6R,1'R,2'S)
      5,6,7,8-tetrahydrobiopterin, we demonstrate that error backpropagation networks
      can be established that efficiently approximate complicated functional
      relationships such as torsional potential energy surfaces of a flexible molecule.
      Our pilot simulations suggest that properly trained neural networks might provide
      an extremely compact storage medium for quantum chemically obtained information.
      Moreover, they are outstandingly comfortable tools when it comes to making use of
      the stored information. One possible application is demonstrated, namely,
      computation of relaxed torsional energy surfaces.

PMID- 8744569
TI  - Personal computer-based visualization of three-dimensional scalar and vector
      fields: an application to molecular graphics.
AB  - A desktop PC-based graphics package, UNIVIS, for visualization of three
      dimensional numerical data is described. Apart from routine molecular model
      visualization, the package provides for a host of other features such as
      extraction of various surfaces, planar cross-sections of the three-dimensional
      data, and property texturing. Fast rendering and transparency are the strengths
      of the present package. These features are comprehensively discussed. The salient
      features of UNIVIS are presented in the form of visualization of a variety of
      molecular properties, which are of immense importance in understanding molecular
      structure and reactivity patterns.

PMID- 8744570
TI  - VMD: visual molecular dynamics.
AB  - VMD is a molecular graphics program designed for the display and analysis of
      molecular assemblies, in particular biopolymers such as proteins and nucleic
      acids. VMD can simultaneously display any number of structures using a wide
      variety of rendering styles and coloring methods. Molecules are displayed as one
      or more "representations," in which each representation embodies a particular
      rendering method and coloring scheme for a selected subset of atoms. The atoms
      displayed in each representation are chosen using an extensive atom selection
      syntax, which includes Boolean operators and regular expressions. VMD provides a
      complete graphical user interface for program control, as well as a text
      interface using the Tcl embeddable parser to allow for complex scripts with
      variable substitution, control loops, and function calls. Full session logging is
      supported, which produces a VMD command script for later playback. High
      resolution raster images of displayed molecules may be produced by generating
      input scripts for use by a number of photorealistic image-rendering applications.
      VMD has also been expressly designed with the ability to animate molecular
      dynamics (MD) simulation trajectories, imported either from files or from a
      direct connection to a running MD simulation. VMD is the visualization component
      of MDScope, a set of tools for interactive problem solving in structural biology,
      which also includes the parallel MD program NAMD, and the MDCOMM software used to
      connect the visualization and simulation programs. VMD is written in C++, using
      an object-oriented design; the program, including source code and extensive
      documentation, is freely available via anonymous ftp and through the World Wide
      Web.

PMID- 8744571
TI  - MD Display: an interactive graphics program for visualization of molecular
      dynamics trajectories.
AB  - MD Display was developed as a means of visualizing molecular dynamic trajectories
      generated by Amber. The program runs on Silicon Graphics workstations, and
      features a simple user interface, and convenient display and analysis options.
      The program has now been extended to accept input from several other molecular
      dynamics programs.

PMID- 8744572
TI  - Structural basis of p21H-ras molecular switch inhibition by a neutralizing
      antibody.
AB  - The ras oncogene product p21 functions as a molecular switch in the early section
      of the signal transduction pathway that is involved in cell growth and
      differentiation. When the protein is in its GTP-complexed form it is active in
      signal transduction, whereas it is inactive in its GDP-complexed form. The
      transforming activity of p21ras is neutralized by the mouse monoclonal antibody
      Y13-259, possibly by preventing GDP-GTP exchange. A molecular model of the
      variable fragment of Y13-259 has been derived using a knowledge-based prediction
      approach and computer-assisted modeling techniques. An analysis of this model
      while complexed with p21ras/(GDP) indicated that the two molecular switch regions
      are constrained by complex formation. Antibody binding inhibits GDP-GTP exchange
      through a mechanism of steric hindrance. Having identified necessary bound sites
      for inhibition, and explored their electrostatic properties, it should be
      possible to proceed with the design of antibody mimics as therapeutic agents in
      cancer control.

PMID- 8744573
TI  - MOLMOL: a program for display and analysis of macromolecular structures.
AB  - MOLMOL is a molecular graphics program for display, analysis, and manipulation of
      three-dimensional structures of biological macromolecules, with special emphasis
      on nuclear magnetic resonance (NMR) solution structures of proteins and nucleic
      acids. MOLMOL has a graphical user interface with menus, dialog boxes, and on
      line help. The display possibilities include conventional presentation, as well
      as novel schematic drawings, with the option of combining different presentations
      in one view of a molecule. Covalent molecular structures can be modified by
      addition or removal of individual atoms and bonds, and three-dimensional
      structures can be manipulated by interactive rotation about individual bonds.
      Special efforts were made to allow for appropriate display and analysis of the
      sets of typically 20-40 conformers that are conventionally used to represent the
      result of an NMR structure determination, using functions for superimposing sets
      of conformers, calculation of root mean square distance (RMSD) values,
      identification of hydrogen bonds, checking and displaying violations of NMR
      constraints, and identification and listing of short distances between pairs of
      hydrogen atoms.

PMID- 8744574
TI  - Peripheral blood T cell subsets as prognostic indicators of chemotherapy outcome
      in AIDS patients with large cell lymphoma.

PMID- 8744575
TI  - Restricted tissue distribution of extralesional Kaposi's sarcoma-associated
      herpesvirus-like DNA sequences in AIDS patients with Kaposi's sarcoma.
AB  - Specific herpesvirus-like DNA sequences have been found in Kaposi's sarcoma (KS)
      lesions of AIDS patients, suggesting that a novel gamma herpesvirus, homologous
      to Epstein-Barr virus and herpesvirus saimiri, could be implicated in the
      pathogenesis of KS. To better understand the role of this putative etiological
      agent, named Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus
      8 (HHV-8), we investigated by the polymerase chain reaction (PCR) the presence of
      viral DNA sequences in various organs obtained at autopsy from seven AIDS
      patients with KS and six without KS. For each sample, to exclude positive results
      due to visceral KS dissemination, the presence of microscopic foci of KS cells
      was rules out by histology and CD34 immunohistochemistry on serial frozen
      sections immediately adjacent to those employed for DNA extraction. PCR and
      nested PCR were performed with primers specific for the HIV-8 330 Bam fragment
      originally described by Chang et al. (Science 1994;266:1865-1869). As quality
      control, the extracted DNA was amplified with primers for human beta-globin. All
      KS legions were HHV-8 positive. In addition, extralesional KSHV DNA sequences
      were detected in seven of seven lymphoid organs and in five of five prostate
      glands of KS patients. Normal skin was positive in three of five cases and bone
      marrow in two of three tested cases, all other tissues being negative by PCR and
      nested PCR. By contrast, no virus was detected in tissue samples of AIDS cases
      without KS. The restricted organ distribution here documented argues for a
      selective tissue tropism of HHV-8 in vivo in AIDS patients and suggests that in
      the infected host lymphoid organs and the prostate gland may represent privileged
      sites of viral latency and persistence.

PMID- 8744576
TI  - Effect of interleukin 12 on in vitro HIV type 1 replication depends on clinical
      stage.
AB  - CD8-depleted PBMCs from 20 HIV-1-seropositive donors were incubated in the
      presence of no cytokines, rIL-2, rIL-12, or both. HIV-1 replication, measured by
      culture supernatant p24 Ag, was increased to a comparable extent by either rIL-2
      or rIL-12 in five of seven asymptomatic subjects and was not induced by either
      cytokine in the remaining two asymptomatic subjects. Recombinant IL-2 induced
      increased p24 in cultures from 8 of 13 symptomatic subjects, but rIL-12 did only
      in cell lines from 5 symptomatic subjects and then only marginally. In IL-2
      containing cultures from subjects with minor symptoms of HIV infection, the mean
      p24 Ag was 320 +/- 217 pg/ml versus 27 +/- 6 in IL-12-containing cultures (p =
      0.03). When rIL-12 was added with rIL-2, p24 Ag levels were reduced fourfold
      compared to cultures from this group incubated with only rIL-2 (p = 0.03).
      Neither cytokine had much effect on viral replication in CD8-depleted PBMCs from
      subjects who had had a major AIDS infection, although the number of CD4 cells in
      four of six of those cultures was markedly reduced. IL-4, IFN-gamma, and IL-10
      production induced by exposure to IL-2 and/or IL-12 were also measured. In CD8
      depleted cultures from all infected asymptomatic donors and from some symptomatic
      donors, addition of rIL-12 to rIL-2 decreased IL-4 and increased both IFN-gamma
      and IL-10 production. Cytokine-induced production of IL-4, IFN-gamma, and IL-10
      was greater in cultures from asymptomatic donors than in cultures from
      symptomatic subjects. Our results suggest that IL-12 immunotherapy may be
      complicated by enhancement of viral expression in asymptomatic individuals.

PMID- 8744577
TI  - Virus load as a marker of disease progression in HIV-infected children.
AB  - The relationship of virus load to clinical disease progression in HIV-infected
      children remains to be elucidated. In this study, HIV-1 proviral DNA load was
      determined in peripheral blood mononuclear cells (PBMCs) by the quantitative
      competitive DNA polymerase chain reaction assay (QC-PCR) in 47 HIV-infected
      children subdivided by age (group I, < or = 2 years; group II, > or = 5 years),
      who were further categorized to include 12 rapid progressors (RP, age < or = 2
      years, Centers for Disease Control [CDC] defined clinical category C and/or
      immune category 3, or death before age 2 years) and slow progressors (SP, age >
      or = 5 years, excluding CDC categories C and/or immune category 3). Significantly
      higher mean proviral copies/10(3) PBMCs were detected in group I versus group II
      (75.4 +/- 104.3 and 13.0 +/- 17.8 respectively, p < 0.0001) and in RP (158.0 +/-
      118.2) as compared to either SP (11.8 +/- 18.8, p < 0.0001) or other age-matched
      infected children (20.3 +/- 38.8, p < 0.0001). Thus HIV-infected children appear
      to have a higher cell-associated virus load early in life, especially in
      association with rapid disease progression.

PMID- 8744578
TI  - Synergistic antiviral action of ribonucleotide reductase inhibitors and 3'-azido
      3'-deoxythymidine on HIV type 1 infection in vitro.
AB  - Ribonucleotide reductase inhibitors reduce the cellular supply of DNA
      precursors(dNTP) by interfering with their de novo synthesis. A secondary effect
      is the stimulation of the uptake and phosphorylation of extracellular
      deoxynucleosides, including their analogs, e.g., 3'-azidothymidine (AZT). Both
      effects are relevant to HIV replication, which requires dNTP and is impaired by
      the triphosphate of AZT. Earlier we demonstrated that ribonucleotide reductase
      inhibitors--hydroxyurea, and two deoxycytidine analogs specifically active in
      lymphoid cells--increased the phosphorylation of AZT in CEM cells by prolonging
      the S phase of the cell cycle. Here we tested the effects of long-term treatments
      on HIV proliferation in CEM cells and stimulated human lymphocytes infected with
      HIV-1IIIB. Treatment with low doses of AZT (0.05-0.1 microM) and either
      hydroxyurea (25-100 microM) or 2'-azido-2'-deoxycytidine (0.25-4 microM) lasted 2
      weeks, during which p24 in the culture medium was monitored. Noninfected CEM
      cells were treated in parallel to measure the inhibition of cell growth,
      distribution along the cell cycle, dNTP pool size, and level of tritiated AZT
      phosphorylation. A clear synergism between AZT and ribonucleotide reductase
      inhibitors was observed at nontoxic doses that induced only minor changes in the
      cellular parameters measured. The reductase inhibitors by themselves interfered
      with replication only at doses that inhibited cell proliferation.

PMID- 8744580
TI  - Membrane glycolipids and human immunodeficiency virus infection of primary
      macrophages.
AB  - The membrane glycolipids galactosylceramide (GalCer) and sulfatide (SGalCer) have
      been reported to act as receptors of human immunodeficiency virus (HIV) on CD4-
      cell lines. We show here that these glycolipids are present on CD4+ cells
      purified from human blood and on in vitro-differentiated monocyte-derived
      macrophages (MDMs). We investigated the role they could play in HIV infection.
      Glycolipids of MDMs were characterized at the molecular level by immunolabeling
      and thin-layer chromatography immune overlay, using a panel of human-, rabbit-,
      or murine-specific antibodies. GalCer and SGalCer were expressed at the surface
      of MDMs as assessed by indirect immunofluorescence and flow cytometry analysis,
      and they could be characterized with specific antibodies in the cellular
      glycolipid extracts in addition to GM1, GM3, and GD1b gangliosides. Recombinant
      125-I-labeled gp160 specifically bound to GalCer, SGalCer, GM1, and GM3 as well
      as to phospholipids (phosphatidylethanolamine and phosphatidylserine) from MDM
      extracts. Anti-SGalCer monoclonal antibodies (MAbs), but not anti-GalCer
      antibodies, entailed limited (30-40%) but significant inhibition of gp160 binding
      to MDMs. However, the four human anti-SGalCer MAbs and the three murine or rabbit
      ant-GalCer antibodies tested did not inhibit HIV infection of MDMs, in contrast
      to CD4 antibody anti-Leu3a tested in parallel. These findings suggests that
      although HIV envelope glycoprotein can bind to SGalCer and GalCer from CD4+ MDM
      extracts, these glycolipids do not apparently act as HIV coreceptors nor are they
      involved in HIV infection of these cells.

PMID- 8744581
TI  - Immunodominant glycoprotein 41 epitope identified by seroreactivity in HIV type 1
      infected individuals.
AB  - A highly conserved gp41 epitope (amino acid sequence ELDKWA) has been described
      to elicit antibodies neutralizing a broad variety of HIV-1 strains. We analyzed
      the antibody reactivity of HIV-1-infected individuals from Argentina and Sweden
      to overlapping synthetic peptides covering aa647-684 of HIV-1 MN gp41. An
      immunodominant antigenic determinant was discovered in the C-terminal region
      adjacent to the ELDKWA sequence. Most of the sera from both Argentina and Sweden
      reacted only with peptides representing this region. Two other patterns of
      reactivity were also observed: some sera reacted only with peptides spanning the
      central region of gp41, including the ELDKWA sequence; other sera reacted with
      both the central and C-terminal regions. Differences in reactivity were noted
      between Argentinian and Swedish sera in terms of peptides covering the central
      region. In addition, to determine the amino acids essential for antibody binding,
      seroreactivity against a set of substitution peptides covering the immunodominant
      epitope was studied. Results obtained indicated that carboxyl amino acids WNWFDI
      close to the ELDKWA sequence were the most important for antibody binding.
      Ability of sera, tested for peptide reactivity, to neutralize HIV-1 was also
      analyzed. High antibody reactivity to the central region was frequently found in
      sera with high neutralizing titers. This observation was not seen when
      seroreactivity to peptides spanning the C-terminal region was analyzed. These
      results suggest that the immunodominant epitope C terminal to the ELDKWA sequence
      is not involved in inducing neutralizing antibodies.

PMID- 8744579
TI  - Safety and immunogenicity of Env 2-3, a human immunodeficiency virus type 1
      candidate vaccine, in combination with a novel adjuvant, MTP-PE/MF59. NIAID AIDS
      Vaccine Evaluation Group.
AB  - We investigated the safety and immunogenicity of a candidate HIV-1 vaccine, Env 2
      3 (Chiron Biocine Co.), in combination with an adjuvant emulsion, MF59, with or
      without an additional immune modulator, MTP-PE 78 healthy HIV-1-seronegative
      adults. Sixteen subjects participated in a dose escalation study of MTP-PE in
      MF59 without Env 2-3, given at 0 and 1 months; 48 subjects participated in a
      study of a fixed dose of 30 micrograms of Env 2-3 in MF59 with increasing doses
      of MTP-PE (0, 5, 10, 25, 50, and 100 micrograms), and 14 subjects participated in
      a study of 100 micrograms of Env 2-3 in MF59 without MTP-PE. Subjects were
      assigned to study groups under a randomized, double-blind allocation. Subjects
      received immunization at 0, 1, and 6 months, and had the option of receiving a
      fourth dose at 12-18 months. Env 2-3 in MTP-PE/MF59 was associated with
      significant reactogenicity, in that severe, although self-limited systemic and/or
      local reactions occurred in 15 of 30 vaccinees. In contrast, Env 2-3 in MF59
      without MTP-PE was relatively well tolerated, and severe local and/or systemic
      reactions occurred in only 2 of 18 subjects. Env 2-3 stimulated serum antibodies
      to HIV-1 envelope protein (gp120) as detected by Western blot in 39 of 43
      subjects and to HIV-1 virus lysate by EIA in 28 of 43 subjects after three
      injections. The majority of subjects also developed EIA antibodies to recombinant
      gp120 (SF-2), gp120 (LAI), and V3 peptide (SF-2). Neutralizing antibodies to the
      homologous SF-2 strain developed in 30 of 43 and 27 of 34 subjects, and fusion
      inhibition antibodies in 25 of 43 and 15 of 36 subjects after three and four
      injections, respectively. Lymphoproliferative responses to the immunogen, Env 2-3
      were observed in over 80% of the vaccinees examined, and CD4+ cytotoxic T cell
      activity directed against HIV-1 was noted transiently in 2 of 20 vaccinees.
      Addition of MTP-PE to Env 2-3 or increasing the dose of Env 2-3 from 30 to 100
      micrograms did not augment immunogenicity. Env 2-3 in MF59 was well tolerated and
      immunogenic in HIV-1-seronegative individuals. The addition of MTP-PE
      significantly increased reactogenicity, but had little, if any, effect on
      immunogenicity.

PMID- 8744582
TI  - Modulation of CD3-gamma gene expression after HIV type 1 infection of the WE17/10
      T cell line is progressive and occurs in concert with decreased production of
      viral p24 antigen.
AB  - HIV-1 infection of WE17/10, an IL-2-dependent CD4+ human T cell line, abrogates T
      cell receptor (TCR)/CD3 expression due to a transcription level defect in the CD3
      gamma chain gene. Kinetic examination of surface receptor density reveals that
      these complexes are progressively reduced early after HIV-1 infection as the
      cells transition from TCR/CD3hi-->TCR/CD3lo-->TCR/CD3-. The passage from
      TCR/CD3hi reversible TCR/CD3lo is characterized by a steady decrease in receptor
      density from 100 to 50% of control values with similar kinetic for all of the
      viral variants tested. This first phase in TCR/CD3 downmodulation was found to
      occur in concert with a decrease in viral p24 antigen production. The switch from
      TCR/CD3- is distinguished by the conversion of individual cells to the receptor
      negative phenotype. Although broad kinetic differences in this second phase were
      observed between viral variants, its onset was consistently accompanied by a
      further reduction in virus production. In some of the HIV-1-infected WE17/10 cell
      lines, surface receptor expression was spontaneously upregulated during the
      second phase of infection, reversing the progression from TCR/CD3(-)-->TCR/CD3lo-
      >TCR/CD3hi. Thus, in HIV-1-infected WE17/10 cells, changes in CD3-gamma gene
      transcription are accompanied by altered viral p24 antigen production and the
      resulting modulation of surface receptor expression can be summarized by the
      formula: TCR/CD3hi reversible TCR/CD3lo reversible TCR/CD3-.

PMID- 8744583
TI  - Deletion of the nef gene abrogates the ability of SIV smmPBj to induce acutely
      lethal disease in pigtail macaques.
AB  - Simian immunodeficiency virus (SIV) infection in macaque species is typically
      associated with the development of a progressive immunodeficiency disease,
      similar to human AIDS, resulting in death of animals in months to years after
      infection. In contrast, a variant virus, termed SIVsmmPBj, induces an acute
      disease in macaques, resulting in death in 5 to 14 days after infection.
      Previously, we have shown that several viral determinants contribute to the
      pathogenesis of this disease. The present study was undertaken to evaluate the
      role of Nef in the pathogenesis of SIVsmmPBj-induced acute disease. A molecular
      clone of SIVsmmPBj was generated that contains a deletion in the nef coding
      region (PBj6.6 delta nef). Virus derived from this molecular clone was tested
      with the parental virus, PBj6.6, in replication studies in pigtail macaque and
      rhesus macaque peripheral blood mononuclear cells (PBMCs). In general, PBj6.6
      delta nef displayed markedly reduced replication abilities when compared with
      PBj6.6; the only exception being in stimulated pigtail macaque PBMCs, where
      replication kinetics were nearly identical. In addition, PBj6.6 delta nef was
      unable to induce the proliferation of peripheral blood mononuclear cells (PBMCs)
      in vitro, a unique characteristic of acutely pathogenic SIVsmmPBj. Inoculation of
      this virus into pigtail macaques resulted in infection, but did not result in any
      detectable acute disease. These studies suggest that Nef is an important viral
      determinant in the pathogenesis of SIVsmmPBj-induced disease, and further suggest
      that Nef plays a significant role in viral replication in vivo.

PMID- 8744584
TI  - HTLV infection in ELISA-negative blood donors.
AB  - Human T lymphotropic viruses (HTLVs) have a limited spread in the general
      populations of Western countries. Consequently, the transfusional risk for HTLV
      is consider to be low in Italy and the screening for anti-HTLV-I/II antibodies
      has not yet been introduced. In 1992, 1087 blood donors attending a transfusional
      center in northern Italy underwent anti-HTLV-I/II screening carried out by means
      of two different ELISA tests. Eleven individuals who were negative at the first
      test were borderline at the second, eight of them showing reactivity to Western
      blot (WB). Polymerase chain reaction (PCR) for the detection of HTLV DNA,
      subsequently performed on the peripheral blood mononuclear cells of these 11
      subjects, was positive in the same 8 WB-reactive donors. Five of them were
      infected by HTLV-II, and three by HTLV-1. Our results confirm that the
      sensitivity of the ELISA tests actually used for the detection of HTLV-I/II
      antibodies is low, and that HTLV-infected blood donors may be frequently
      undetected. Moreover, in our study population, the prevalence of HTLV infection
      (0.73%) was greater than that which might be expected from the existing
      seroepidemiological data in Italy.

PMID- 8744585
TI  - env gene sequences of primary HIV type 1 isolates of subtypes B, C, D, E, and F
      obtained from the World Health Organization Network for HIV Isolation and
      Characterization.

PMID- 8744586
TI  - Improving the science and art of risk assessment.

PMID- 8744587
TI  - Risk estimation--an overview: disease risk estimation based upon animal
      bioassays.
AB  - Much more could be written about the issues addressed here, as well as about
      issues that are not even mentioned. The goal was to present a brief overview of
      some of the techniques and issues in quantitative health risk assessment based
      upon animal data. Hopefully, this overview will provoke some attention to
      specific in risk assessment that require more research. Perhaps the bibliographic
      references given will lead to other papers.

PMID- 8744588
TI  - A toxicologist's view of cancer risk assessment.

PMID- 8744589
TI  - Empirical and biologically based models for cancer risk assessment.

PMID- 8744590
TI  - Noncancer risk assessment: reproductive toxicology.
AB  - In summary, the concerns that environmental and other agents are causing adverse
      effects on reproductive function in humans are real, although the risk is not
      necessarily well characterized. The range of concerns for the types of effect
      that agents might have on reproduction span the full range of reproductive
      events. There is a fairly high background of reproductive disease in humans which
      decreases the sensitivity for identifying agents that have a subtle, but adverse,
      effect on reproductive performance of humans. Because our animal studies identify
      a large number of agents that cause some adverse reproductive effect at the dose
      levels tested, the concern is raised about the oversensitivity of animal models
      for predicting adverse effects in humans. Until we better understand the biology
      underlying the reproductive process of humans and animals, it will be difficult
      to make animal studies more specific in their predictiveness. Continued research
      to better understand the biology of reproduction in humans and animals should
      help to identify the types of data generated in animals that are most predictive
      of an adverse effect in humans.

PMID- 8744591
TI  - Developmental toxicity risk assessment: consensus building, hypothesis
      formulation, and focused research.
AB  - Risk assessment for developmental toxicity has become more defined over the last
      decade and the most recent EPA guidelines for developmental toxicity risk
      assessment were published in 1991. Development of approaches for risk assessment
      in this area have relied on building of consensus opinion among experts about the
      interpretation of developmental toxicity data. These discussions have aided in
      strengthening the scientific basis for risk assessment for developmental
      toxicity, including the default assumptions that must be used when more complete
      information on mechanisms of action and pharmacokinetics are unavailable. Such
      discussions continue on both a national and international basis. The EPA risk
      assessment guidelines outlined several major areas of research needed to
      strengthen risk assessment for developmental toxicity and led to the formulation
      of hypotheses to be tested in focused research projects. Several major research
      efforts have focused on dose-related mechanisms and biologically based modeling
      of specific agents, physiologically based pharmacokinetic models of pregnancy
      that can be scaled across species, and the influence of dose and duration of
      exposure on developmental outcomes, as well as the delineation of specific
      biomarkers of adverse developmental effects. Although such research initiatives
      will require a long-term effort, it is important that attention be focused now on
      those approaches that can improve the risk assessment process to avoid continued
      reliance on default approaches that have been used for the past 30 years or more.
      The impact of the EPA Guidelines for Developmental Toxicity Risk Assessment has
      been widespread. One of the main purposes for developing risk assessment
      guidelines by EPA was to communicate procedures to risk assessors inside the
      agency in an effort to promote consistency. In addition, the guidelines were to
      communicate to those outside the agency in private industry and other regulatory
      agencies how EPA would evaluate and interpret data. The developmental toxicity
      guidelines have standardized terminology used in developmental toxicity risk
      assessments. They also have influenced the revision of testing guidelines and the
      writing of new guidelines, such as the developmental neurotoxicity testing
      guidelines. More extensive use of developmental toxicity data within the RfD/RfC
      process was influenced by the guidelines, as well. More recently, the risk
      assessment guidelines have had a major impact on the harmonization of
      international testing and risk assessment guidelines through cooperative efforts
      with the World Health Organization under the auspices of the International
      Program on Chemical Safety (IPCS) and the Organization for Economic Cooperation
      and Development (OECD). We foresee these types of interagency and international
      cooperative efforts continuing as we attempt to make more efficient use of the
      limited resources available for testing, risk assessment, and research to better
      understand and prevent developmental toxicity.

PMID- 8744592
TI  - Receptor-selective retinoid agonists and teratogenic activity.
AB  - Retinoid mechanism of action is dependent upon interaction with the retinoid
      nuclear RAR and RXR subfamilies of receptors. Study of ligands selective for the
      different receptors or which modify that interaction may provide insight into
      which receptors play roles in or contribute to retinoid teratogenesis. The
      retinoids considered here include in the RAR alpha-selective
      arylcarboxamidobenzoic acid CD 336 (Am580), the RAR beta/gamma-selective
      naphthalenecarboxylic acid CD 135 and the adamantyl-phenylcarboxamidobenzoic acid
      CD 394, the RAR-selective tetrahydrotetra-methylanthracenylbenzoic acid (TTAB)
      SRI 3961, the carboxyphenylretinamide SRI 7167-67, and the RXR-selective
      diarylisopropylidene SR 11217. CD 135 has a 3-fold higher affinity for RAR beta
      when compared with RAR gamma, whereas CD 394 has a 3-fold higher affinity for RAR
      gamma when compared with RAR beta. A separate investigation into potential
      amelioration of retinoid teratogenesis by concomitant administration of the
      cyclohexanetrione (Ro 31-0521) was also conducted. When pregnant hamsters were
      given an oral bolus of CD 336 or CD 135 during the early primitive streak stage
      of gestation, these retinoids proved 60-100 times more potent teratogens than all
      trans-retinoic acid. Intubation of CD 394 resulted in production of terata
      similar to that seen after an equivalent dose of all-trans-retinoic acid.
      Administration of SRI 3961 found this compound 8000 times more potent than all
      trans-retinoic acid, while SRI 7167-67 failed to show any evidence for
      developmental toxicity even after exposure to 105 mg/kg. Studies with the RXR
      selective SR 11217 found it to be far less potent than all-trans-retinoic acid.
      These data point to the conclusion that those retinoids which have no affinity
      for retinoid nuclear receptors also have little potential for induction of
      developmental toxicity at doses which do not also provoke maternal intoxication.
      Comparing in vitro transcriptional activation of wild-type human RAR for the
      supertoxic TTNBP (Ro 13-7410) and TTAB (SRI 3961) with their relative teratogenic
      potency in hamster found that the more toxic congener also had the lower in vitro
      EC50 transactivation value (at ratios approximating their differential toxicities
      measured as administered dose). The RAR beta/gamma-selective CD 135 (TTNN) was
      not as efficient as TTNBP (Ro 13-7410) or TTAB (SRI 3961) in hRAR transactivation
      and CD 135 was less toxic than either Ro 13-7410 or SRI 3961. Although the RXR
      selective SR 11217 failed to elicit terata after moderate doses, malformations
      consistent with those induced by high doses of retinoic acid could be produced
      following a single large bolus of SR 11217. Under the conditions here,
      simultaneous administration of Ro 31-0521 with all-trans-retinoic acid appeared
      to reduce the total percentage of abnormal fetuses seen after exposure to
      retinoic acid alone, but fetal body weights remained depressed and the numbers of
      dead embryos remained elevated, suggesting only limited influence of the
      cyclohexanetrione on retinoid developmental toxicity.

PMID- 8744593
TI  - Evolution and current status of neurotoxicity risk assessment.
AB  - The U.S. EPA neurotoxicity risk assessment guidelines define neurotoxicity as the
      capacity of chemical, biological, or physical agents to cause an adverse
      functional or structural change in the peripheral or central nervous system.
      Chemical-induced changes in the structure or persistent changes in behavior,
      neurochemistry, or neurophysiology of the nervous system are regarded as
      neurotoxic effects. Reversible effects occurring at doses that could endanger
      performance in the workplace, are associated with a known neurotoxicological
      mechanism of action, covary with a known neurotoxicological effect, or are latent
      effects uncovered by pharmacological or environmental challenge, could be
      considered to be neurotoxic effects. It should also be noted that even if a
      chemical-induced change in neurobiological function or structure does not meet
      the criteria established for a neurotoxic effect, the alteration could still be
      considered as adverse and used in a regulatory decision. Adverse effects detected
      by neurobiological procedures should not, however, necessarily lead to the
      conclusion that the chemical is a neurotoxicant. At the present time,the default
      RfD uncertainty factor approach is used for neurotoxicological data. A number of
      other safety factor approaches and quantitation dose-response models have been
      proposed for evaluating neurotoxicological data. However, a very limited number
      of comparisons have been made between the RfD approach and alternatives. In
      summary, neurotoxicity is one of several noncancer and points currently being
      used by regulatory agencies. The effective utilization of neurobiological
      measures to assess chemical-induced changes in the structure and function of the
      nervous system depends on properly designed studies and elimination of potential
      confounding variables that obscure interpretation of data from toxicological
      studies.

PMID- 8744594
TI  - Reducing uncertainty in risk assessment by using specific knowledge to replace
      default options.
AB  - This paper has advocated the development of specific scientific information,
      especially information on the mechanisms of action of chemicals, to use in place
      of default options in assessing human cancer risks. Four examples have been
      discussed that build largely on information from the CIIT research program. These
      four examples are worthy of consideration as a group, with a view to developing
      insights for increasing the effectiveness and efficiency of obtaining such data
      in the future and, most of all, to increase their acceptance for use instead of
      default options. In my view, key features of all four examples are that the data
      are framed within an exposure-dose-response paradigm and that there is a clear
      linkage to the end point of concern-cancer. As the number of techniques available
      for making observations at the cellular and molecular levels continues to
      increase at a rapid pace, linking these observations to the health end points of
      concern such as cancer is going to be increasingly important, especially in
      enhancing the value of the observations for risk assessment purposes. Equally as
      important, the mechanistic observations must be linked to realistic exposures and
      associated tissue dose that can be related to realistic human exposure scenarios.
      In my opinion, the likelihood of obtaining information of value for risk
      assessment purposes using the most sophisticated of molecular and cellular
      techniques will be of limited value if the exposures or doses are not
      realistically linked to those likely to be encountered by humans. The mechanism
      of alpha 2u-globulin nephropathy and its association with kidney tumors in male
      rats and the conclusion that the male rat kidney tumor findings are not
      applicable to assessing human cancer risk is an example of a qualitative
      decision. I suspect this may be a somewhat unusual case. As one looks across the
      various mammalian species used for experimentation and makes comparisons with
      humans, a unifying theme is the relative abundance of similarities. Indeed, this
      is a major argument for the use of laboratory animals to obtain information
      relevant to humans. Nonetheless, vigilance to differences among species is
      important. When differences are observed, we must capitalize on them to better
      understand the underlying biological mechanisms that mediate the differences. If,
      as I have suggested, laboratory animal species are more like than different from
      humans in their basic biological characteristics, there is a rationale for
      continuing to use laboratory animals as sources of data to help assess human
      risks of exposure to chemicals. It follows from this that quantitative
      differences among species such as observed with both formaldehyde and 1,3
      butadiene assume major importance for assessing human risks. In my opinion,
      quantitation of the likely human carcinogenic potency of chemicals is of major
      importance. It is not sufficient to simply classify chemicals with regard to the
      likelihood of their being human carcinogens, as done by IARC (1994) and U.S. EPA
      (1986). IARC has placed more than 60 chemicals or processes (such as coke
      production) in group 1, carcinogenic to humans; more than 50 in group 2a,
      probably carcinogenic to humans; and 250 in group 2b, possibly carcinogenic to
      humans. This rank order implies differing levels of concern for three categories.
      However, even this rough three-bin system does not convey a very clear picture as
      to the degree of concern that should be accorded a given chemical for producing
      cancer. For example, the chemicals categorized as group 1, human carcinogens,
      using potency estimates developed by the U.S. EPA differ in potency by roughly 4
      orders of magnitude. For example, a lifetime cancer risk is 6.2 x 10(-2) per
      micrograms/m3 for bischloromethyl ether and 8.3 x 10(-6) for benzene (NRC, 1994).
      Differences such as this offer strong arguments for complementing simplistic
      hazard identification schemes such as the IARC and EPA carcinogen classification
      systems w

PMID- 8744595
TI  - Reality versus extrapolation: an academic perspective of cancer risk regulation.

PMID- 8744596
TI  - Making regulatory decisions across the food ingredient spectrum.
AB  - Today, safety evaluation of food ingredients must be performed for a wide
      spectrum of substances and over a wide range of potential human exposures. Some
      of the traditional approaches to toxicological safety evaluation are not
      appropriate for certain of the more extreme examples across this spectrum. Yet
      the public and the regulated industry continue, rightfully, to expect that the
      system will function efficiently and effectively in their behalf. FDA must expand
      the range of its available tools to address the unique questions presented by
      nontraditional food chemicals, while maintaining the scientific credibility and
      integrity of the regulatory decision process that has protected public health for
      many decades. The safety standard that these materials must meet has not changed.
      Yet the types of questions pertinent to safety decisions may indeed be different
      than those traditionally used.

PMID- 8744597
TI  - Thresholds of toxicological concern based on structure-activity relationships.

PMID- 8744598
TI  - Bioassay designs for validating biologically based mathematical models of
      carcinogenesis for risk assessment.
AB  - Bioassays that include various types of discontinuous exposure to carcinogens are
      somewhat rare and are far from routine. However, discontinuous-dosing groups
      represent a valuable enhancement of the ordinary bioassay design. My hope is that
      efforts to include discontinuous-exposure groups in cancer-bioassays will become
      widespread, and that discontinuous-dosing designs will eventually be a matter of
      routine. To me, such designs represent an easy (although perhaps costly) way to
      increase the sophistication of the tumor incidence data for model fitting, and to
      provide valuable data for validating (or perhaps invalidating) postulated
      mathematical models of the cancer process. Certainly discontinuous-dosing data at
      least provide a valuable ancillary resource to be utilized along with data on
      postulated mechanisms in the effort to implement biologically based models of the
      cancer process for quantitative risk assessment. Such data might even be
      indispensible.

PMID- 8744599
TI  - Biological markers and risk assessment.
AB  - Biological markers provide the opportunity to rapidly advance the field of risk
      assessment for both workers and the general population. Markers of exposure allow
      much more accurate assessment of exposure than currently possible using
      mathematical models of dispersion and uptake. Markers of effect can lead to the
      prediction of disease sufficiently early to avoid adverse outcomes in workers or
      the general population. Linkage of predictors of effect with markers of exposure
      can provide dose-response information of unique relevance to the problems of
      extrapolating from high to low dose and from animals to humans. Biological
      markers of susceptibility allow definition of the populations for whom risk
      characterization is particularly of importance. Development of biological markers
      suitable for risk assessment requires careful validation and faces impediments
      due to the overreliance of regulators on mathematical models, which inhibits the
      development of new bioscience, and due to misplaced concerns about ethical
      experimental exposures of humans to environmental levels of pollutants. The path
      to developing biological markers of exposure, effect, or susceptibility of value
      in risk assessment is primarily through improving basic biomedical understanding.

PMID- 8744600
TI  - Some thoughts about the use and communication of toxicology information.

PMID- 8744601
TI  - Risk proposals of the 103rd Congress.

PMID- 8744602
TI  - International harmonization of approaches to risk assessment: will resolution of
      scientific issues alone lead to success?

PMID- 8744603
TI  - Hazard evaluation in risk assessment: whatever happened to sound scientific
      judgment and weight of evidence?

PMID- 8744604
TI  - Lipid oxidation on foods.
AB  - This review discusses the basic chemical reactions that affect food flavor
      quality. Although there are many reactions that can lead to the deterioration of
      quality in foods, this review focuses on lipid oxidation and how it adversely
      affects flavor principals. It also presents technological advances for studying
      the basic mechanism of lipid oxidation, for measuring its intensity, and for
      retaining food quality. The food commodities that provide the subject matter for
      this review include vegetable oils, legumes, cereal grains, eggs, beef, lamb,
      poultry, seafoods, and catfish. The methodologies for assessing food quality form
      a multidisciplinary approach that includes primarily instrumental analysis by
      direct gas chromatography, chemical analysis by the TBA test, and sensory
      analysis by quantitative descriptive determinations. The author hopes that the
      information presented in this review is applicable to food commodities not
      discussed.

PMID- 8744605
TI  - Nonenzymatic deamidation of food proteins.
AB  - Many cereal proteins, such as wheat, corn, and oat proteins, have high levels of
      the amide-containing amino acids, glutamine and asparagine. These side chains are
      susceptible to hydrolysis of the amide bond, which leads to release of ammonia
      and transformation to acidic groups. The released ammonia has been implicated in
      the formation of aroma compounds and pigments because of its participation in the
      Maillard browning reaction. The conversion of the amide groups to acid groups may
      partially unfold the protein, resulting in an amphiphilic molecule that can be
      used as a surface active agent or emulsifier by food processors. This review
      provides general information on the factors that affect deamidation of proteins
      as well as the implications of deamidation for food processing.

PMID- 8744606
TI  - Fish flavor.
AB  - This article reviews features of flavor in three groups of fishes and summarizes
      them as follows: (1) fresh saltwater fish are nearly odorless because they
      contain a small quantity of volatiles; (2 freshwater fish give off pyrrolidine
      and earthy-odor compounds, which are responsible for their maturity and
      surrounding water pollution, and (3) euryhaline fish exhibit a variety of
      unsaturated carbonyls and alcohols derived from enzymatic and nonenzymatic
      oxidation of polyunsaturated fatty acids (PAs). These features are discussed, as
      are the effects of different enzymatic activities on PA oxidation and the effects
      of pH on mechanisms of formation of the volatiles. The monotonous volatile
      constitution of saltwater fish is likely caused by an unknown antioxidation
      system restraining the fish from oxidizing. The variety of constitution of
      euryhaline fish, especially that of anadromous fish under spawning conditions,
      could result from the loss of that system. The thermal environments of heated
      foods are also reviewed. The basic environment of fish, which allows the
      formation of flavor compounds, is discussed to confirm the volatiles found in
      unheated fish.

PMID- 8744607
TI  - Pass the parcel--the public hospital sector in action.

PMID- 8744608
TI  - Anti-lamin autoantibodies and the clinical utility of autoimmune serology.

PMID- 8744609
TI  - Proarrhythmic complications of sotalol.

PMID- 8744610
TI  - Pulmonary vascular aspects of systemic sclerosis.

PMID- 8744611
TI  - The first gene for an idiopathic epilepsy: a fruitful collaboration of Australian
      clinical research and molecular genetics.

PMID- 8744612
TI  - Recent advances in the understanding, diagnosis and management of multiple
      sclerosis.

PMID- 8744613
TI  - Clinical associations of anti-lamin autoantibodies.
AB  - BACKGROUND: The clinical associations of anti-lamin autoantibodies were first
      described in 1973. Since then a number of individual case reports and two small
      series have been published. These have suggested an association with connective
      tissue disorders and autoimmune liver disease. AIMS: To identify the clinical and
      laboratory associations of anti-lamin autoantibodies in an Australian population.
      METHODS: Retrospective review of routine antinuclear antibody testing between
      1990-1994 for characteristics linear staining of nuclear envelope on indirect
      immunofluorescence on HEp-2 cells with clinical status defined by retrospective
      review of case records. RESULTS: Twenty-eight patients were identified and the
      clinical status of 27 patients defined. Eleven patients had associated IgG anti
      cardiolipin antibodies; anti-phospholipid syndrome was present in nine. Seven
      further patients had liver disease; five had autoimmune liver disease, with
      associated autoantibodies. The remaining nine patients had a diverse group of
      diseases. There was no correlation between the titre of the autoantibody and
      clinical status. An association with anti-cardiolipin antibodies was found
      although the cause remains obscure. CONCLUSION: Anti-lamin autoantibodies, as
      identified by indirect immunofluorescence, are associated with a diverse group of
      diseases but particularly with anti-phospholipid syndrome and liver disease.
      Testing for anti-phospholipid antibodies and more specific markers of systemic
      lupus erythematosus and autoimmune disease, for example anti-dsDNA antibodies,
      anti-smooth muscle antibodies and anti-mitochondrial antibodies should be pursued
      when anti-lamin autoantibodies are detected.

PMID- 8744614
TI  - Sotalol proarrhythmia: a report of five cases and an audit of the use of a
      sotalol in a teaching hospital.
AB  - BACKGROUND: Polymorphic ventricular tachycardia is an uncommon complication of
      sotalol use. AIMS: The aims of this study were: (1) to report five cases of
      sotalol proarrhythmia and (2) to audit the use of sotalol in a teaching hospital
      population. METHODS: Five patients with sotalol proarrhythmia (defined as new
      ventricular arrhythmias associated with sotalol administration) were identified
      over an 18 month period. Sotalol use for patients admitted to the John Hunter
      Hospital was audited over a six month period with 85 patients (55 males)
      identified from the pharmacy database. Medical records were reviewed and the
      details of treatment including sotalol dose and indication determined. Creatinine
      clearance was estimated by the Cockcroft and Gault regression equation. RESULTS:
      The audit indicated that sotalol was prescribed predominantly for management of
      atrial arrhythmias (80%). Paroxysmal atrial fibrillation was the most common
      indication (71%). Although female patients were older (72 +/- 13 vs 62 +/- 15
      years, p < 0.001) and had a lower creatinine clearance (55 +/- = 24 vs 82 +/- =
      32 mg/minute, p < 0.001) than male patients, they were prescribed similar doses
      of sotalol (206 +/- 112 vs 193 +/- 93 mg/day). The ratio of sotalol dose to
      creatinine clearance was higher in female patients (4.0 +/- 2.6 vs 2.16 +/- 1.5,
      p < 0.01). The five patients with proarrhythmia (torsades de pointes in four
      patients and polymorphic ventricular tachycardia in one patient) were all female.
      Daily sotalol dose (odds ratio for each 160 mg tablet 4.9 [95% confidence
      interval 1.5-16] and female gender (p < 0.01) were significant risk factors for
      proarrhythmia. CONCLUSION: Sotalol dose was not appropriately adjusted for
      creatinine clearance which is age and gender dependent. Female patients have an
      increased risk of proarrhythmia and should receive lower doses of sotalol.

PMID- 8744615
TI  - Risk factors for ill-health in a remote desert-dwelling aboriginal community in
      Western Australia.
AB  - BACKGROUND: Living in small, isolated groups may promote health for Aborigines if
      traditional lifestyles are followed, but overall health risks in such communities
      are inadequately documented. AIM: To document health status of a remote
      Aboriginal community with reference to nutrition, cardiovascular risks, renal
      disease and infections and to identify areas where health might be improved.
      METHODS: All residents of a small community in the Great Sandy Desert underwent
      medical examinations, anthropometry and measurement of blood pressure.
      Investigations included cholesterol, triglycerides, glucose, insulin, creatinine,
      lipoprotein (a), apolipoprotein E phenotype, angiotensin-converting enzyme
      genotype, urinalysis, stool microscopy (children), liver function tests and full
      blood examination. RESULTS: Children (n = 26) were undernourished while 14% of
      adults (n = 51) were underweight, 22% overweight and 40% of women and 13% of men
      were obese with central obesity in 90% of women and 48% of men. Fifteen per cent
      of the group were hypertensive. Insulin levels were increased in 55% of subjects,
      total cholesterol in 21% and triglycerides in 56%, while HDL was decreased in
      78%. Angiotensin-converting enzyme and apolipoprotein E typing and lipoprotein
      (a) did not suggest increased cardiovascular risk. Proteinuria was present in 39%
      of subjects, haematuria in 49% and definite or possible urinary tract infections
      in 30%. Faecal parasites were prevalent and a history of infections, including
      sexually transmitted diseases, was common. CONCLUSIONS: Increased cardiovascular
      risk, nutritional disorders, renal disease and infections are major problems in
      this community which had relocated several years previously from a mission
      environment closer to western influences, including alcohol.

PMID- 8744616
TI  - Variable hyperhomocysteinaemia phenotype in heterozygotes for the Gly307Ser
      mutation in cystathionine beta-synthase.
AB  - BACKGROUND: A deficiency of cystathionine beta-synthase (CBS) activity is the
      most frequent cause of homocystinuria, an autosomal recessive disease with
      multiple clinical manifestations. Mutations in the CBS gene have been reported in
      several patients with homocystinuria. AIMS: To establish the molecular basis of
      CBS deficiency in a female patient with pyridoxine non-responsive homocystinuria,
      and to apply the findings to genetic screening of her family members. METHODS:
      The entire coding region of the CBS cDNA was amplified by PCR and used for direct
      sequence analysis. Mutant alleles were confirmed by direct sequence analysis of
      PCR-amplified genomic DNA, and by a combination of single strand conformation
      polymorphism and temperature gradient gel electrophoresis analysis. RESULTS: The
      proband was homozygous for a G919A base transition which predicts the
      substitution of serine for glycine at codon 307 in the CBS protein (G307S). The
      parents (both of Irish background) were heterozygotes for the G307S allele, while
      an asymptomatic sibling had normal CBS sequence, Plasma homocysteine, assessed
      after an oral methionine load, indicated the mother clearly had moderate
      hyperhomocysteinaemia, whereas the father had normal concentrations of
      homocysteine. This is the first report of a normal methionine load test in a
      proven heterozygote for a CBS mutation which causes severe homocystinuria in the
      homozygote. Other factor(s) may have contributed to hyperhomocysteinaemia in the
      mother. The G307S allele has been reported in other patients and appears to be a
      common allele among families of Celtic origin.

PMID- 8744617
TI  - Radiofrequency ablation of idiopathic ventricular tachycardia.
AB  - BACKGROUND: Radiofrequency ablation (RFA) has been shown to be very effective in
      the treatment of supraventricular tachycardias and has replaced surgical
      ablation. Only a few reports of RFA for idiopathic ventricular tachycardia (VT)
      have appeared in the literature during the last two years. AIM: This paper
      presents our experience with RFA for idiopathic VT in 19 patients. MATERIAL: The
      age range of patients was 22-60, with a mean of 37.9 years. Twelve out of 19 were
      females, two patients had cardiac failure due to almost incessant VT while the
      rest had normal left ventricular function. Twelve patients had VT arising from
      the right ventricle (RV); of these, nine were from the outflow tract, two from
      the RV apex, and one from the mid-anterior RV. Seven patients had VT arising from
      the left ventricle (LV); of these, five were from the inferobasal portion of the
      septum and two were from the anterolateral area. METHODS: In all patients the
      diagnostic study and therapeutic RFA were combined in a single procedure.
      Pacemapping was used to guide the site of RFA in patients with VT arising from
      the RV. Local activation time (LAT), Purkinje potentials (PP) and pacemapping
      were used to guide RFA in those patients with LV septal tachycardias. RESULTS: A
      total of 21 RF procedures were performed in 19 patients and 15 out of 19 patients
      had successful VT ablation. Ten of the 12 patients with RV tachycardias and all
      five patients with LV septal (left axis, right bundle branch block) tachycardias
      were successfully ablated. One patient with mid anterior RV VT required two
      attempts for successful ablation. One patient with RV outflow tract (RVOT) VT
      could not be ablated despite two attempts. Two patients with LV tachycardias
      arising from the antero-lateral LV could also not be ablated. During a follow up
      period of two to 16 months none of the successful patients had recurrence of VT.
      The number of RF applications was one to 27, mean 10; fluoroscopy times were four
      to 75, mean 26.9 minutes. CONCLUSION: Idiopathic VT frequently arises from the
      RVOT and inferobasal portion of the LV septum. These tachycardias can be
      diagnosed on clinical and ECG grounds. RFA for idiopathic VT arising from these
      areas has a high success rate and this mode of treatment should be considered as
      a nonpharmacological curative treatment for symptomatic patients.

PMID- 8744618
TI  - Detection of carriers of haemophilia A: use of bioassays and restriction fragment
      length polymorphisms (RFLP).
AB  - BACKGROUND: Haemophilia A is a sex-linked bleeding disorder carried by unaffected
      females. Currently, the two main methods used for the determination of carrier
      status in women from families with haemophilia A are bioassays and DNA-based
      assays using restriction fragment length polymorphisms (RFLP). AIM: The aim of
      this paper was to assess the current usefulness of these two methods. METHODS:
      Bioassays measured factor VIII coagulation activity by a two-stage coagulation
      assay and von Willebrand antigen by immunoelectrophoresis. RFLP were determined
      with two intragenic probes (p114 and p486) and two linked probes (St14 and DX13).
      Data were analysed using a Bayesian analysis to allow for all possible
      recombination events. We also incorporated an estimate for the risk of mosaicism
      into calculations in isolated haemophilia families. Both bioassays and RFLP were
      used to determine carrier status in 63 women, 31 from known haemophilia families
      and 32 from families of isolated cases. The techniques were assessed for their
      ability to classify the patients as normal (p < 0.2) or carrier (p > 0.7). Where
      applicable, intron 22 inversion was also tested. RESULTS: In the known families,
      six women could not be classified after bioassay, but all could be classified by
      RFLP. Of the 32 women from families of isolated cases, eight were unclassified by
      bioassay and 12 were not definitely classified using RFLP. However, RFLP was
      useful in determining that a recent mutation had occurred in six of the eight
      families in which DNA from the grandparents was available. CONCLUSION: For
      diagnosis of carriers of haemophilia, RFLP is the preferred method in familial
      haemophilia, but is less useful in isolated haemophilia.

PMID- 8744619
TI  - Cost effectiveness of day stay versus inpatient radiofrequency (RF) ablation for
      the treatment of supraventricular tachyarrhythmias.
AB  - BACKGROUND: It is well established that radiofrequency (RF) ablation is the most
      cost effective treatment strategy for patients with supraventricular tachycardia.
      Previous cost estimates assumed at least an overnight stay following RF ablation.
      Day stay RF ablation however appears to be a safe alternative. AIMS: The aim of
      this study was to compare day stay and inpatient catheter ablation in terms of
      cost, efficacy and safety. METHODS: This was a retrospective cost effectiveness
      analysis. The study population consisted of 25 consecutive patients who underwent
      day stay RF ablation and 25 consecutive patients who underwent inpatient RF
      ablation (historical controls). Economic analysis was based upon a detailed
      clinical costing. RESULTS: The mean overall cost per patient of inpatient RF
      ablation in 1994 Australian dollar values is $2354 (SD, $642) compared with $1876
      (SD, $595) for day stay RF ablation (p < 0.01). Day stay RF ablation is a cost
      effective alternative to inpatient RF ablation.

PMID- 8744620
TI  - Antiplatelet therapy and the prevention of thrombosis.

PMID- 8744621
TI  - The mast cell and inflammation.

PMID- 8744622
TI  - Schistosomiasis at Christchurch Hospital, 1989-94.

PMID- 8744623
TI  - Development of multidrug resistant tuberculosis following supervised care: a case
      for directly observed therapy.

PMID- 8744624
TI  - Adjuvant chemotherapy for non-metastatic osteosarcoma of the extremities in two
      New Zealand cancer centres.

PMID- 8744625
TI  - Hereditary fructose intolerance in an adult.

PMID- 8744626
TI  - Clozapine-induced neuroleptic malignant syndrome: another inconclusive case
      report.

PMID- 8744627
TI  - Use of nebulised prostacyclin to ascertain reversibility of secondary pulmonary
      hypertension.

PMID- 8744628
TI  - Legionella longbeachae pneumonia and Henoch-Schonlein purpura.

PMID- 8744629
TI  - Resolution of pyoderma gangrenosum using tacolimus (FK-506)

PMID- 8744630
TI  - Sulphasalazine-induced agranulocytosis successfully treated with filgrastim.

PMID- 8744631
TI  - A subtle presentation of acute rheumatic fever in remote northern Australia.

PMID- 8744632
TI  - Does activated protein C resistance increase the risk of systematic embolism in
      non rheumatic atrial fibrillation?

PMID- 8744633
TI  - The Illawarra study to evaluate the Chemcard Cholesterol Test.

PMID- 8744634
TI  - Personality process and therapeutic action: advances in psychodynamic concepts
      and measurement of the interface.

PMID- 8744635
TI  - Reliability and convergence of three concepts of narcissistic personality.
AB  - UNTIL recent years, the personality disorders have been relatively unexplored
      compared to other psychiatric diagnoses. Over 15 years ago, there was little
      agreement on the diagnosis of borderline personality disorder (Perry and Klerman
      1978), but efforts to specify the constructs and respective criteria for the
      borderline diagnosis spurred a plethora of systematic research. The result is
      that, next to antisocial personality disorder, borderline has become one of the
      best-documented and validated personality disorders (Perry and Vaillant 1989).
      One important shift has been that good descriptive studies have gradually led to
      studies of etiological factors, such as childhood physical and sexual abuse, and
      severe neglect (Herman et al. 1989; Perry and Herman 1992), which in turn have
      led to empirically based treatment approaches (Herman 1992; Perry et al. 1990).
      Despite inclusion in The Diagnostic and Statistical Manual of Mental Disorders
      (DSM-III and DSM-III-R), narcissistic personality is still at the beginning of
      this process of description, empirical testing, and validation (Gunderson et al.
      1991). This study empirically examines three descriptions of narcissistic
      personality in order to look for common underlying dimensions that may have
      etiological and treatment significance.

PMID- 8744636
TI  - Primary attachment in female adolescents: association with depression, self
      esteem, and maternal identification.
AB  - DURING the past two decades, infant and child research has accumulated
      considerable support for John Bowlby's views on the importance of early
      attachment experience (1958, 1969, 1973, 1980, 1988). Briefly stated, Bowlby's
      theory conceptualized infant-mother attachment as a primary instinct, separate
      from other physiological needs (such as hunger or sex), and serving the purpose
      of continuing proximity to a caregiver. Children generate "internal working
      models of attachment" that influence the organization of their attachment-seeking
      behaviors (Bowlby 1980). During childhood these models are being actively and
      continuously constructed by the child. Toward the end of adolescence, however,
      they tend to become stable and serve as a template for later attachments
      throughout the life cycle. Narrative reconstruction of these attachment models by
      young adults recalling their childhood can be considered as a dynamic "summary
      statement" regarding the child's attempts and caregiver's responses in the
      maintenance of attachment bonds, rather than as verifiable facts (Main and Kaplan
      1985).

PMID- 8744637
TI  - Self as subject: a formulation and an assessment strategy.
AB  - IN James' view the self has two components, the self as subject, the I-self, or
      the self as knower; and the self as object, the me-self, or the self as known
      (James 1968). They are the dynamic and imagistic aspects of the self,
      respectively. Until recently, as Harter emphasizes in her comprehensive review
      (Harter 1983), quantitative studies of the self have focused almost exclusively
      on the self as object. They have explored such aspects of self-concepts as the
      self as independent, likable, or competent; contrasts between real and ideal
      images of the self; and developmental changes in self-concepts.

PMID- 8744638
TI  - Psychological mindedness.
AB  - THERE is a consensus in the psychotherapy literature that the patient dimension
      of psychological mindedness is important to working within all forms of
      psychoanalytically oriented therapy. Silver (1983) offered a comprehensive
      definition of psychological mindedness stating that the capacity includes: The
      patient's desire to learn the possible meanings and causes of his internal and
      external experiences as well as the patient's ability to look inwards to
      psychical factors rather than only outwards to environmental factors....[and] to
      potentially conceptualize the relationship between thoughts, feelings, and
      actions. (p. 516).

PMID- 8744639
TI  - Dimensions and predictors of patient response to interpretation.
AB  - THE technique of interpretation is central to psychodynamic psychotherapy.
      Empirical information about effective interpretive technique would be of
      practical value to clinicians. The objectives of this exploratory study were to
      describe the immediate response to interpretation and identify the features of
      interpretation that are predictive of the response.

PMID- 8744640
TI  - Change in object and self-representations in long-term, intensive, inpatient
      treatment of seriously disturbed adolescents and young adults.

PMID- 8744641
TI  - Countertransference in the treatment of patients with eating disorders.
AB  - THE term countertransference has undergone considerable change in meaning in
      recent decades. Freud (1910/1957) defined countertransference as the emotional
      reaction of the analyst to a patient's transference. It was seen as the
      unresolved needs and conflicts of the therapist, often unconscious, which
      interfered with his/her understanding of the patient. Recently, Abend (1989)
      chronicled the shift in the definition of the term and noted Kernberg's (1965)
      more totalistic" description of countertransference. In Kernberg's view, the
      therapist's reactions have more to do with the patient's often intense
      transference and with the therapist's capacity to withstand the subsequent stress
      and anxiety, than with any particular problem from the patient's past. Abend
      (1989) concluded that most clinicians refer to countertransference in this
      revised way and used the term quite broadly to denote "all those reactions of the
      analyst to the patient that may help or hinder treatment" (Slakter 1987, p. 3).

PMID- 8744642
TI  - Participation of IL-2 and direct cell cytotoxicity in the modulation of GvH
      reaction in mice infected with Listeria innocua.
AB  - Listeria innocua can intensify the development of local GvH reaction in a
      semiallogeneic system in mice. This phenomenon is observed in (BALB/c x AKR)F1
      mice intraperitoneally injected with the live bacteria on the 7th day before the
      transfer of BALB/c spleen cells. The local GvH reaction develops as strongly as
      in normal hybrid recipients given the parental cell graft in the presence of
      exogenous interleukin 2 (IL-2). The development of the reaction is associated
      with an intensive increase of the direct cytotoxicity of lymph node cells which
      is also markedly enhanced after the bacteria injection itself. IL-2 seems to play
      a relevant role in the development of local GvH reaction in L. innocua-injected
      mice.

PMID- 8744643
TI  - Characterization of cellular components in the peritoneal fluid and in the
      endometrial tissue of women with endometriosis.
AB  - The presence of leukocyte subpopulations was demonstrated in peritoneal fluid and
      in endometrial tissue of women with (n = 16) and without (n = 20) endometriosis.
      Peritoneal fluid samples were also assayed for effects on lymphocyte
      proliferation in vitro. Peritoneal fluid leukocyte profiles were observed to be
      different between these groups. The most significant elevations in total number
      of leukocytes, macrophages and lymphocytes and natural killer (NK) cells were
      observed in women with endometriosis. In normal eutopic endometrium T lymphocytes
      (CD3+), macrophages (Ki-M1+) and NK cells (CD16- CD5+) were present. In contrast
      aggregates of NK cells (CD16+ CD56-) were only identified in ectopic endometrial
      tissue. Mitogen-induced lymphocyte proliferation was significantly higher in the
      presence of peritoneal fluid from patients with severe stage of endometriosis as
      compared with other samples. Our data indicate that disturbances of the cellular
      immune system may lead to progression of endometriosis in female peritoneal
      cavity.

PMID- 8744644
TI  - Presentation of antigen by B cell subsets. V. Effect of interleukin 7 (IL-7) and
      interleukin 10 (IL-10) on phenotype and antigen presenting function of immature B
      cells.
AB  - In this communication we demonstrate that B cells from CBA/N mice with x
      chromosome-linked immunodeficiency and B cells from newborn mice, that have very
      limited ability to present antigen to antigen-specific T cells lines, acquire
      this function following preincubation with IL-7 or IL-10. These interleukins do
      not affect the antigen presenting function of B cells from normal, adult CBA
      mice. Incubation of B cells from xid and newborn mice with IL-7 or IL-10 but not
      with IL-2 induces expression of Lyb-5 marker on these cells. The study shows that
      the property of IL-7 and IL-10 to induce antigen presenting cell (APC) activity
      in immature B cells is associated with appearance of Lyb-5 antigen on these
      cells.

PMID- 8744645
TI  - CD4+ T cells from mice primed for humoral immunity to sheep erythrocytes (SRBC)
      specifically inhibit cell-mediated immunity and vice versa.
AB  - The aim of this study was to demonstrate whether development of the humoral or
      cellular immunity to sheep erythrocytes (SRBC) can be inhibited by a transfer of
      antigen-specific CD4+ T cells isolated from mice exhibiting cellular or humoral
      response. For generation of the humoral immune response and suppressor T cells
      for the cellular immunity, mice were immunized with a high dose of SRBC
      intraperitoneally (i.p.). On the other hand, for development of the cellular
      response and generation of T cells with inhibitory activity in relation to the
      humoral response, mice were immunized subcutaneously (s.c.) with SRBC emulsified
      with complete Freund's adjuvant or intravenously (i.v.) with low dose of SRBC
      (10(5)). We showed that depletion of CD4+ but not CD8+ T cells in the populations
      of transferred T cells abolished their inhibitory activity. The phenomenon of
      this suppression was dependent on a dose of T cells transferred and was antigen
      specific, since T cells specific for chicken erythrocytes did not inhibit anti
      SRBC-response. The data indicate the importance of antigen specific CD4+ T cells
      in the mutual regulation of the two major type of the immune response.

PMID- 8744646
TI  - Antitumor activity of bestatin and thiorphan in mice.
AB  - We have investigated the effect of bestatin and thiorphan on growth of murine
      transplantable tumors, survival time, activity of natural killer (NK) cells and
      macrophages in mice. The injections of thiorphan at the does of 0.5 or 5
      micrograms per mouse retarded tumor growth and prolonged survival period in B16
      melanoma bearing animals. Pretreatment with naloxone (an unspecific antagonist of
      opioid receptors) blocked the tumor growth inhibition induced by the treatment
      with bestatin and thiorphan what could suggest a contribution of endogenous
      enkephalin in this antitumor effect. The percentage of mice bearing B16 melanoma
      tumor in the group treated with thiorphan at doses of 0.5, 5 or 50 micrograms per
      mouse was lower in comparison with control animals in a dose-dependent manner.
      The treatment with thiorphan at concentrations of 0.4-1.6 mg/ml inhibited growth
      of cultured in vitro B16 melanoma cell in comparison with control culture.
      Thiorphan added to the medium at concentration of 0.5 microgram/ml or
      administered 4 times at the dose of 0.5 microgram/mouse augmented NK lymphocyte
      activity.

PMID- 8744647
TI  - Peanut agglutinin (PNA) binding glycoproteins on human urothelial cell lines of
      different grades of transformation.
AB  - PNA-reactive sites, representing mainly unmasked Thomsen-Friedenreich (TF)
      antigen, are predictors of invasive transitional cell carcinoma. The present
      studies were undertaken in order: 1) to quantify the expression of PNA-reactive
      sites on well-characterized human urinary bladder cell lines belonging to two
      different transformation grades (TGr II and TGr III); 2) to identify PNA-binding
      glycoproteins that are restricted in their expression to tumorigenic and invasive
      urothelial cell lines. Flow cytometry studies revealed significant differences
      between TGr II and TGr III cell lines. The mean fluorescence intensities of TGr
      III, tumorigenic and invasive cells, were in the range of 28.4 to 57.3 arbitrary
      units. The TGr II cells exhibited several fold lower fluorescence intensity: 9.8
      arbitrary units for HCV 29 cell line and 13.1 arbitrary units for Hu 609 cells.
      Neuraminidase treatment, increasing PNA-binding to TGr II as well as in TGr III
      cell lines, revealed the presence of cryptic PNA-binding sites. The number of
      cryptic PNA-binding sites seemed to be similar in TGr II and in TGr III cells
      and, therefore, only add to the total number of PNA-binding sites on native,
      untreated cells. Binding of 125I-PNA to all cellular proteins resolved by SDS
      PAGE and transferred to nitrocellulose showed multiple bands. The TGr III cells
      lines, after desialylation, were characterized by the presence of two major PNA
      binding components represented by diffuse bands with apparent molecular mass
      about 68-79 kDa and 116-156 kDa, respectively, and two weakly stained bands with
      apparent molecular mass of 51 kDa and 60 kDa. Both cell lines representing TGr II
      expressed high molecular mass PNA-binding component of 207 kDa. They were further
      characterized by the weaker staining intensity of 116-156 kDa glycoproteins as
      compared to TGr III cell lines.

PMID- 8744648
TI  - Growth inhibition of transplantable tumors in mice by mIL-2-secreting murine
      plasmocytoma cells used alone or in combination with a cytostatic agent.
AB  - The non-tumorigenic cells of X63-Ag8.653 mouse plasmocytoma line transfected with
      murine interleukin 2 cDNA (X63-mIL-2) served us as the source of the cytokine to
      induce or to augment antitumor response in syngeneic BALB/c or semisyngeneic
      (CD2F1) mice challenged subcutaneously with either "wild" line tumor cells
      (X63/0) or with non-related methylcholantrene induced BFS1 fibrosarcoma of BALB/c
      mice. When applied peritumorally in several injections (2 to 6) to mice with non
      advanced stages of the tumors, IL-2-secreting cells were able to cause tumor
      growth retardation in most of the treated mice and to induce tumor rejection in
      some of them. The combination chemoimmunotherapy was attempted in mice with
      advanced BFS1 fibrosarcoma using compound CBM-4A (the bromoanalog of ifosfamide)
      administered at various time (4 h or 3, 5 or 7 days) before the first of two
      local injections of transfected cells. The strategy proved to be more efficient
      in the tumor growth inhibition as compared with the cytostatic alone.

PMID- 8744649
TI  - Influence of a rat kidney perfusion using the anti-MHC class II monoclonal
      antibody and reduced dose of 15-deoxyspergualine on the allogeneic graft
      survival.
AB  - One of the main factors inducing rejection of the allogenic graft are the donor
      MHC-class II antigens. In this study, the allogenic rat renal graft survival
      after the blockage of MHC-class II positive cells was analyzed and compared with
      the effectiveness of the recipient treatment with 15-deoxyspergualine (15-DOS).
      It was found that the DA (RT1 a) rat kidney perfusion with the anti-MHC class II
      monoclonal antibody (MoAb 29A1--Kiel) allowed to prolong survival of the graft in
      the LEW (RT1 1) recipient (9.6 +/- 0.8 vs. 7.7 +/- 0.5 days). Our another study
      demonstrated that the 14 day treatment of the LEW recipient with 15-DOS at the
      dose of 0.5 mg/kg body weight can induce tolerance to the grafted kidney from the
      DA strain. The dose of 0.2 mg/kg body weight of 15-DOS prolonged the graft
      survival only to a small extend (16.5 +/- 0.5 days). In contrast, the combination
      of the graft pretreatment with MoAb 29A1 with the application of the reduced dose
      of 15-DOS to the LEW recipient allowed to further prolong the graft survival
      (97.4 +/- 59.0 days, n = 5). In 3 cases, the long-time (close to 150 days) graft
      survival was obtained. The above presented results suggest that the blockade of
      the MHC-class II antigens can reduce the immunogenicity of the graft. Although
      this procedure was not sufficient to induce tolerance, it allowed to minimize the
      immunosuppressive treatment.

PMID- 8744650
TI  - Effect of benzisoselenazolones and organic diselenides on graft versus host
      reaction and immunoglobulins levels in chickens.
AB  - Two week old chickens were treated once daily for 5 days with AE8--1-pyridyl-1,2
      benzisoselenazol-3(2H)-one, AE22--bis-2-(N-phenyle-carboxamido) 1 pyridyl
      diselenide and AE31--bis(phenylo-diselenide with R3 = CONHC18H37). Their whole
      blood alone or blood mixed with thymus cells were used to generate graft versus
      host (GvH) reaction in 15 day old chicken embryos. The treatment of the chickens
      with the compounds stimulated the GvH reaction modifying activity of the donor
      cells as measured by increase of the spleen weight of the recipient chicken
      embryos. On the other hand, treatment with these compounds inhibited the IgG or
      IgM production in chickens immunized with human albumin.

PMID- 8744651
TI  - Immunotropic activities of benzisoselenazolones and organic diselenides in mice.
AB  - We have investigated the immunotropic effects of 23 seleno-organic compounds (8
      benzisoselenazolones, 3 benzisoselenazolone oxides and 12 organic diselenides).
      All of the compounds increased the rosette formation of sheep red blood cells
      (SRBC) with spleen cells obtained from thymectomized C53BL/6 mice and incubated
      in vitro in the presence of imuran. Furthermore, 16 of the compounds were also
      assayed in vitro in the hydrocortisone test performed with C57BL/6 mouse
      thymocytes. It was found that all of them significantly protected the cells
      against hydrocortisone induced cytotoxicity. Also in the Jerne's assay, performed
      in 129Ao/Boy mice pretreated in vivo with 3 selected compounds 5 days before
      immunization with SRBC, the stimulation of plaque forming cells (PFC) was
      observed. Only one compound (AE22, an analog of piroxicam) was found to be
      inhibitory in this assay. In contrast, in the graft versus host (GvH) assay
      performed in hybrid mice the donor lymphoid cells obtained from C57BL/6 mice
      pretreated with 9 selected seleno-organic compounds, suppressed the GvH reaction
      in the recipient hybrid mice. Thus, in all of the immunotropic assays except the
      GvH reaction in adult mice, the seleno-organic compounds were found to have
      immunostimulating activities.

PMID- 8744652
TI  - Oral heparin in the treatment of rheumatoid arthritis.
AB  - Heparin was administered orally in 10 patients with rheumatoid arthritis. The
      treatment resulted in clinical improvement in all cases (significant reduction in
      the number of tender and swollen joints and morning stiffness). This was
      associated with a decrease in erythrocyte sedimentation rate (8/10 patients) and
      cholesterol in all patients, although the differences were not significant.
      Recent data indicate that heparin can bind cytokines with potent immune
      modulatory action (e.g. TNF-alpha, interferon gamma etc.). Thus, neutralization
      of their action on target cells could be partially responsible for the beneficial
      effects reported. Moreover, heparin inhibits T cell traffic to a site of antigen
      by blocking enzymes digesting the extracellular matrix and interfering with
      selection activity. The results of our preliminary study suggest that heparin,
      given per os, may have immunomodulatory properties with potential application in
      human disease.

PMID- 8744653
TI  - 2-Chlorodeoxyadenosine (2-CdA) in the treatment of patients with relapsed chronic
      lymphocytic leukemia.
AB  - This study attempts to characterize the response of patients with chronic
      lymphocytic leukemia (CLL) to the purine analog 2-chlorodeoxyadenosine (2-CdA).
      We have treated 10 patients with 2-CdA, at a dose 0.05-0.1 mg/kg/daily, for 7
      days as a 2-hour infusion. Mean age was 54.6 years (range, 34-68 years). Mean
      time from diagnosis to treatment with 2-CdA was 37.0 months (range, 8-84 months).
      All the studied patients had received preliminary therapy consisting of other
      than 2-CdA chemotherapeutic regimens. Eight out of 10 patients had Rai stage III
      IV disease. Four patients had Coombs positive hemolytic anemia before 2-CdA
      treatment. Seven patients responded to 2-CdA. Two complete remission (CR) and 5
      partial remission (PR) were achieved. All patients but one with Coombs positive
      autoimmune positive hemolytic anemia achieve complete resolution of hemolysis.
      Severe neutropenia was frequent, and serious infections were noted in 20%, 43%
      and 50% of cases during the first, second and third course of 2-CdA,
      respectively. We conclude that 2-CdA is an effective agent in relapsed CLL
      patients, particularly in cases complicated by autoimmune hemolytic anemia.

PMID- 8744654
TI  - Effect of repeated treatments with cladribine (2-chlorodeoxyadenosine) on blood
      counts in multiple sclerosis patients.
AB  - We report the results of blood morphology monitoring of 11 remitting-relapsing
      multiple sclerosis patients who received repeated treatments with cladribine (2
      chlorodeoxyadenosine). The drug was given once, daily, subcutaneously (5 mg) or
      orally (10 mg) for 5 consecutive days, as 6 monthly courses followed by one or
      two additional courses at 3 or 6 month intervals. The treatments were well
      tolerated, although many patients suffered from incidental upper respiratory
      tract infections, most of which occurred during the last 6 months of the
      observation period. One patient had recurrent infections, including an episode of
      urosepsis. All infections responded to standard therapy with antibiotics.
      Progressive lymphocyte reduction to 1000/microliters on average, and clear, but
      clinically insignificant drop in thrombocytes, was observed. Granulocyte counts
      were sometimes markedly elevated. A few patients developed macrocytosis, but none
      required transfusion. With our dosing and schedule, cladribine seems relatively
      safe in multiple sclerosis patients.

PMID- 8744655
TI  - 2-Chlorodeoxyadenosine: lack of synergism with cyclosporine A and tacrolimus (FK
      506).
AB  - New clinically useful drug, 2-chlorodeoxyadenosine (2-CdA), was found to be a
      potent immunosuppressant both in vitro and in vivo. The present study examines
      the in vitro interactions of classical immunosuppressive agents--FK 506 and
      Cyclosporine A (CsA) with 2-CdA at the level of T and B cells proliferation,
      expression receptor for interleukin 2 (R-IL-2) and Ig synthesis. No synergism
      between 2-CdA and either FK 506 or CsA was demonstrable.

PMID- 8744656
TI  - Continuous versus split-course irradiation for lung cancer. Immunological
      implications.
AB  - The therapeutical irradiation for lung cancer causes profound disturbances of
      host's general immunocompetence, the cellular immunodepression being the dominant
      finding. It is thought that split-course technique holds certain advantage over
      the continuous irradiation, since the former includes an interruption of 4 week
      duration, thus allowing the lymphopoietic system to recover to a certain degree.
      In this report, we compared the radiotherapy-due alterations of several
      parameters of cellular immunity (the number and function of total T cells, active
      T cells and the cells of monocyte/macrophage lineage), immediately after the
      completion of therapy in either continuously (n = 13) or split-course-irradiated
      (n = 12) lung cancer patients. All patients had received the total dose of 60 Gy.
      Both therapeutical techniques caused alterations of the parameters tested: the
      significant decrease of the total and active T cells and their proliferative
      responses, while the phagocytic activity and the number of mononuclear phagocytes
      were increased, the latter being affected to a lesser extent in split-course
      treated patients. Our results suggest that both techniques have similar
      immunodepressant effect on the cellular immunity of lung cancer patients.

PMID- 8744657
TI  - Comparison of morphine with and without fentanyl for epidural analgesia after
      major abdominal surgery.
AB  - BACKGROUND AND OBJECTIVES: The study compared bolus injection of fentanyl versus
      morphine to supplement epidural infusion of morphine for pain relief after major
      abdominal surgery. METHODS: Postoperative epidural analgesia was activated by
      patient request for pain relief. Thirty patients were given a loading dose
      (random assignment, double-blind administration) of 2 mg of morphine (group M, n
      = 15) or 60 micrograms of fentanyl (group F/M, n = 15), along with an epidural
      infusion of 0.2 mg/h of morphine. Additional boluses of 0.5 mg of morphine (group
      M) or 25 micrograms of fentanyl (group F/M) were given according to individual
      need. If patients were painfree for 3 hours, the infusion rate for morphine was
      reduced by 50%. RESULTS: Both treatments provided similar degrees of analgesia,
      although onset time was shorter for the F/M group (P < .05). To obtain 24 hours
      of analgesia, group M needed 18.0 mg of morphine, while group F/M needed 4.7 mg
      of morphine and 1.48 mg of fentanyl. For group M, mean serum concentrations of
      morphine decreased from 18 ng/mL at 1 hour from the start of treatment to 5 ng/mL
      at 24 hours. For group F/M, serum morphine stayed at approximately 4 ng/mL, but
      serum fentanyl increased from 0.28 ng/mL at 5 minutes to about 0.8 ng/mL at 16
      hours. CONCLUSIONS: When fentanyl is added continuously to epidural morphine, the
      resulting higher total serum levels of opioids during prolonged treatment may
      increase the risk of respiratory depression. Combining the two opioids for the
      loading dose, however, may be valuable to shorten the onset time of analgesia.

PMID- 8744658
TI  - The regional anesthesia "learning curve". What is the minimum number of epidural
      and spinal blocks to reach consistency?
AB  - BACKGROUND AND OBJECTIVES: Wide variability exists in the amount of regional
      anesthesia practice to which residents are exposed during training. The number of
      attempts at various blocks before a trainee becomes proficient at performing
      these regional anesthetic techniques is not known. This study addresses the
      question: What is the minimum number of blocks a resident must perform to reach
      consistency during training in these techniques? METHODS: Every regional
      anesthetic technique attempted by all beginning CA-1 anesthesiology residents (n
      = 7) during their first 6 months of training (July 1993 to December 1993) were
      recorded on a daily basis. Nonregional anesthetic techniques attempted were
      recorded for comparison. The objective measures used to define the degree of
      success were obtaining cerebrospinal fluid during attempted spinal anesthesia,
      subsequent anesthetic block during epidural placement, and detection of end-tidal
      carbon dioxide for endotracheal intubation. RESULTS: An average of 77 +/- 9
      epidural anesthetics, 44 +/- 6 spinal anesthetics, and 86 +/- 13 endotracheal
      intubations were attempted during the 6 months of training. The learning curves
      for each technique are of similar shape. Residents show significant (P < .05)
      improvement over baseline after 20 spinal and 25 epidural anesthetics, but a 90%
      success rate is not reached and maintained until 45 spinal and 60 epidural
      anesthetics are performed. CONCLUSIONS: Approximately 20-25 procedures each are
      necessary before improvement in the techniques of spinal and epidural anesthesia
      is demonstrated by residents in training. If a 90% success rate is desired, 45
      and 60 attempts at spinal and epidural anesthesia, respectively, may be
      necessary.

PMID- 8744659
TI  - Spinal analgesia during labor with low-dose bupivacaine, sufentanil, and
      epinephrine. A comparison with epidural analgesia.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this investigation was to evaluate the
      effectiveness and side effects of combined spinal-epidural (CSE) injection of a
      bupiv-acaine-sufentanil-epinephrine mixture during labor as compared with
      epidural analgesia alone. METHODS: In a randomized trial, 63 parturients
      presenting for vaginal delivery received either epidural analgesia (10 mL) with
      12.5 mg bupivacaine plus 10 micrograms sufentanil and 12.5 micrograms epinephrine
      or CSE analgesia with a single subarachnoid injection of 1 mg bupivacaine plus 5
      micrograms sufentanil and 25 micrograms epinephrine (total volume, 2.5 mL). For
      this purpose a 29-gauge BD-Quincke spinal needle was used. All subsequent top-ups
      consisted of 10 mL of the mixture, as used for the patients who received epidural
      analgesia only. RESULTS: Thirteen patients delivered without requesting a second
      injection. The time required to obtain satisfactory analgesia (visual analog
      score < or = 2.5 and/or > 50% improvement) was significantly shorter for those
      who received the subarachnoid mixture than for the epidural analgesia group (4.0
      +/- 0.4 vs 10.4 +/- 0.5 minutes, respectively, P < .001). The duration of
      analgesia was longer for the CSE group (137.4 +/- 11.5 vs 106.4 +/- 11.8 minutes,
      P < .05), with more patients being pain-free for longer than 150 minutes (40 vs
      8%, P < .05). Less bupivacaine was consumed in the group receiving the
      subarachnoid mixture (21.6 +/- 2.0 vs 30.7 +/- 2.1 mg, P < .01). Pruritus was
      more common following subarachnoid than following epidural injection of
      sufentanil (53.1 vs 25.8%, P < .05). Other side effects related to the injected
      drugs, such as motor impairment, hypotension, or nausea or vomiting, were not
      observed. Although all blocks were uneventful, moderate headache compatible with
      postdural puncture headache occurred in two patients of the CSE group, which
      necessitated a blood patch after 5 days. CONCLUSIONS: The CSE mixture induced
      long-lasting analgesia, with fast onset and without motor block or hypotension.
      Pruritus and headache were the major drawbacks of this technique.

PMID- 8744660
TI  - Auditory, ocular, and facial complications of central neural block. A review of
      possible mechanisms.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this review is to draw together a
      collection of uncommon complications of central neural block that affect the
      cranial nerves. There have been a small number of case reports, some of which
      have included a possible mechanism of the nerve dysfunction, but there is no
      prior review that collected them together and discussed the possible mechanisms.
      METHODS: Published case reports were identified by searching Medline of the
      British Medical Association and the Silver Platter CD-ROM library. In addition,
      the Medical Defence Union and Medical Protection Society were contacted to find
      cases that were unpublished but the subject of medical negligence lawsuits.
      RESULTS: The authors collected these cases together to increase awareness of
      alarming complications. If such cases are recognized for what they are, then the
      prognosis is good; however, delayed diagnosis can make them a cause of great
      anxiety and possible litigation. CONCLUSIONS: Increased awareness of these
      complications can decrease the likelihood of litigation by early diagnosis and
      explanation. Their mechanisms are not fully understood but the likely
      possibilities have been discussed. Further work is needed to establish the
      incidence of these problems, as it is likely that many cases are not diagnosed
      and not reported.

PMID- 8744661
TI  - Psychological characteristics of reflex sympathetic dystrophy versus myofascial
      pain syndromes.
AB  - BACKGROUND AND OBJECTIVES: Reflex sympathetic dystrophy (RSD) has sometimes been
      hypothesized to derive from a unique psychological predisposition because of its
      enigmatic features, as well as the profound behavioral and emotional
      characteristics manifested by some patients. This study compares the
      psychological characteristics of RSD and myofascial pain syndrome (MPS) patients
      to discern the extent of any aspects unique to RSD. METHODS: The patients
      included 58 with RSD and 214 with MPS, all of whom completed the Minnesota
      Multiphasic Personality Inventory (MMPI) as well as a pain questionnaire.
      Additional pertinent demographic and clinical characteristics were ascertained.
      RESULTS: The only significant demographic group differences revealed a higher
      proportion of RSD patients not working (P < .05) and a higher proportion of RSD
      patients receiving Workers' Compensation payments (P < .001). The RSD patients
      had shorter duration of pain (P < .01) and were taking fewer pain medications (P
      < .01) than the MPS group, but the two groups had comparable numbers of pain
      related surgeries, pain intensity ratings, perceived ability to cope, and ongoing
      extent of involvement in social or recreational activities. A wide range of
      functioning was in evidence for both groups on the MMPI clinical scales, but with
      duration as a covariate, the RSD group had significantly (P < .05) lower scores
      on the hypochondriasis, depression, hysteria, and psychasthenia scales and higher
      scores on the hypomania scale. The duration covariate was significant (P < .05)
      only for the infrequency (rare responses) and depression scales. Duration and
      certain scale scores were inversely correlated. CONCLUSIONS: With only a few
      exceptions, RSD and MPS patients appear comparable with respect to a wide range
      of demographic, clinical, and psychological functioning indices. A specific
      psychological profile, uniquely neurotic or otherwise, has yet to be demonstrated
      in terms of any etiologic or maintenance factors in RSD.

PMID- 8744662
TI  - Effect of epidural bupivacaine block on midazolam hypnotic requirements.
AB  - BACKGROUND AND OBJECTIVES: The aim of the study was to determine the effect of
      epidural bupivacaine block on midazolam hypnotic requirements. METHODS: Sixty
      unpremedicated, ASA physical status I or II male patients, aged 45-65 years and
      scheduled for elective lower abdominal, pelvic, or lower limb surgery
      participated in this randomized, double-blind, placebo-controlled study. The
      study population was composed of three groups: Before administration of
      midazolam, patients in the first group received an intramuscular injection of 15
      mL saline (M), those in the second group an intramuscular injection of 15 mL 0.5%
      bupivacaine (MIB), and those in the third group an epidural injection of 15 mL
      0.5% bupivacaine at the L3-L4 level (MEB). Loss of the ability to respond to
      verbal command was used as an endpoint for the effect of midazolam injected
      intravenously in predetermined doses (five patients per dose) 30 minutes after a
      bupivacaine (or saline) injection. Midazolam dose-response curves were obtained
      by probit analysis. RESULTS: The midazolam median effective dose values for the
      hypnotic effect were 0.20 mg/kg (95% confidence limit, 0.10-0.27 mg/kg) in the M
      group; 0.10 mg/kg (0.06-0.22 mg/kg) in the MIB group; and 0.04 mg/kg (0.03-0.07
      mg/kg) in the MEB group. The differences between the midazolam median effective
      dose values had high levels of significance: P < .00001 for MEB versus M, P <
      .002 for MEB versus MIB, and P < .01 for MIB versus M. CONCLUSIONS: Epidural
      bupivacaine block profoundly decreases midazolam hypnotic requirements. The most
      likely explanation for this effect is the reduction in afferent input induced by
      the block.

PMID- 8744663
TI  - Comparison of intravenous nalbuphine infusion versus saline as an adjuvant for
      epidural morphine.
AB  - BACKGROUND AND OBJECTIVES: Radical (three-quadrant) hemorrhoidectomy is a major
      anorectal surgery that may necessitate aggressive pain management. This study was
      undertaken to determine whether intravenous nalbuphine infusion as an adjuvant to
      epidural morphine could offer not only a good quality of pain relief but also a
      lower incidence of side effects. METHODS: Sixty patients requiring epidural
      anesthesia for radical hemorrhoidectomy were enrolled in a randomized, double
      blind study. At the end of the surgery, all patients received epidural morphine 4
      mg for relief of postoperative pain. Thereafter, 2 mg and 3 mg of morphine were
      administered via the epidural route at 8 p.m. and 8 a.m., respectively, for a 48
      hour observation period. Patients in group 1 received an adjuvant intravenous
      infusion of nalbuphine 15 micrograms/kg/h, whereas patients in group 2 received
      intravenous saline only. A rescue analgesic of intramuscular meperidine 40 mg
      (every 4 hours) was available for each patient. RESULTS: All patients had
      adequate postoperative pain relief. Cumulative (48-hour) analgesic requirements
      were similar. During the 48-hour observation period, one patient in group 1 and
      six in group 2 demonstrated a PaCO2 above 45 mm Hg. No patient had an SaO2 below
      90%. The incidence of nausea and/or vomiting was 13% in group 1 and 62% in group
      2. The incidence of pruritus was 7% in group 1 and 62% in group 2. CONCLUSIONS:
      The results suggest that intravenous nalbuphine infusion as an adjuvant for
      epidural morphine reduces the incidence of side effects without decreasing the
      quality of pain relief.

PMID- 8744664
TI  - Dual effect of the serotonin agonist, sumatriptan, on peripheral neurogenic
      inflammation.
AB  - BACKGROUND AND OBJECTIVES: Sumatriptan is a novel drug for migraine headache
      pain, which, on the basis of its mechanism of action, may have therapeutic
      potential in other pain states. Sumatriptan inhibits neurogenic inflammation in
      dural vessels by activating the 5-HTIB and 5-HTID inhibitory serotonin (5
      hydroxytryptamine [5-HT]) receptor subtypes on terminals of trigeminal neurons.
      This study was designed to determine the role of sumatriptan in peripheral pain
      mechanisms by detecting whether 5-HTIB and 5-HTID receptors and the recently
      cloned excitatory 5-HT7 receptor, for which sumatriptan displays moderate binding
      affinity, are present in peripheral sensory neurons, and by determining the
      effect of sumatriptan on peripheral neurogenic inflammation. METHODS: A
      polymerase chain reaction (PCR) technique was used to detect mRNA for 5-HT
      receptors in rat lumbar dorsal root ganglia. Rat knee joint plasma extravasation
      was used to determine the effect of sumatriptan on peripheral neurogenic
      inflammation. RESULTS: The mRNA for the sumatriptan-activated receptors 5-HTIB, 5
      HTID, and 5-HT7, was detected in lumbar dorsal root ganglia. In rat knee joint,
      capsaicin-activated C-fibers stimulated plasma extravasation to 273 +/- 62% of
      baseline. Low-concentration sumatriptan (50 nM) significantly inhibited capsaicin
      induced plasma extravasation to 106 +/- 6% of baseline. High-concentration
      sumatriptan (1 microM) significantly enhanced capsaicin-induced plasma
      extravasation to 572 +/- 55% of baseline. CONCLUSIONS: Sumatriptan inhibits
      peripheral neurogenic inflammation, probably via 5-HT1B/1D receptors, and may be
      a novel therapy for inflammatory pain states. However, high concentrations (> 200
      nM) may enhance neurogenic inflammation, possibly by activation of 5-HT7
      receptors, which may explain lack of migraine relief and excessive injection site
      pain in 20-30% of patients treated with sumatriptan.

PMID- 8744665
TI  - Peroneal afferent nerve discharges underlying the behavioral response to the
      formalin test.
AB  - BACKGROUND AND OBJECTIVES: Subcutaneous injection of formalin into the hindpaw of
      the rat results in a biphasic behavioral response consisting of flinching of the
      injected paw. It is postulated that the second-phase response is related to
      sensitization of spinal cord neurons rather than to resumption of peripheral
      nociceptor activity. METHODS: On removal from anesthesia with 3% halothane, 10
      rats were given a subcutaneous injection of formalin (5%, 50 microL) into the
      dorsum of the hindpaw. Behavioral response to the formalin test were observed for
      the subsequent hour. In five sodium pentobarbital-anesthetized rats, peroneal
      afferent nerve activity was recorded for 1 hour following similar subcutaneous
      injection of formalin. RESULTS: During standard formalin testing in
      unanesthetized rats, flinching peaked between 1 and 2 minutes following injection
      (phase 1 response), ceased between 5 and 10 minutes, and recommenced after 15
      minutes with a second peak at 45 minutes (phase 2). In sodium pentobarbital
      anesthetized rats, peroneal afferent nerve activity increased transiently during
      the time course of the phase 1 behavioral response but showed no subsequent
      increase in activity during the ensuing 55 minutes. CONCLUSIONS: The results are
      consistent with the hypothesis that the initial behavioral response to formalin
      injection is mediated by high peripheral nerve activity, while the second phase
      is mediated by sensitization of dorsal horn neurons in conjunction with low
      persistent levels of afferent activity.

PMID- 8744666
TI  - Neurotoxicity of subarachnoid hyperbaric bupivacaine in dogs.
AB  - BACKGROUND AND OBJECTIVES: The study investigated possible neurotoxic effects of
      increasing concentrations and doses of bupivacaine administered into the
      subarachnoid space in dogs. METHODS: Fifty animals were allocated to five
      experimental groups: G1, control; G2, 5 mg 0.5 bupivacaine in 10% glucose
      solution; G3, 10 mg of 1% bupivacaine in 10% glucose solution; G4, 20 mg 2%
      bupivacaine in 10% glucose solution, and G5, 20 mg 2% bupivacaine in water. After
      72 hours of observation, the animals were killed and the spinal cords removed for
      histologic examination by light microscopy. RESULTS: None of the animals showed
      any neurologic clinical disturbance following recovery from spinal anesthesia.
      One case of necrosis of nerve tissue was observed in G3 and four in G4.
      CONCLUSIONS: Increasing concentrations and doses of hyperbaric bupivacaine
      solutions increased the incidence of nerve tissue damage, which did not occur
      with hypobaric solutions. These results should contribute to the further
      understanding of neurologic complications following spinal anesthesia when large
      doses of local anesthetics in hyperbaric solutions are used.

PMID- 8744667
TI  - Bactericidal activity of clinically used local anesthetics on Staphylococcus
      aureus.
AB  - BACKGROUND AND OBJECTIVES: The rate of onset of antimicrobial activity of local
      anesthetics is unknown. Similarly, whether the activity is bactericidal or
      bacteriostatic is also unknown. The antimicrobial activity of local anesthetics
      with preservatives has not been studied. This study investigated the rate and
      potency of the antimicrobial activity of 0.125%, 0.25%, and 0.5% bupivacaine,
      2.0% mepivacaine and 2.0% lidocaine with preservatives, and 2.0% lidocaine
      without preservatives on two strains of methicillin-resistant Staphylococcus
      aureus. METHODS: The pathogen was exposed to each local anesthetic for 1, 3, 6,
      12, and 24 hours at room temperature. The inocula from these suspensions were
      diluted to 1:1,000 with physiological saline to inactivate the antimicrobial
      activity of the local anesthetics and then were cultured for 24 hours at 37
      degrees C on agar plates. RESULTS: Lower colony counts were observed with a 3
      hour or longer exposure to 0.5% bupivacaine in both strains of S. aureus (P <
      .05). The 3-hour exposure reduced the count by approximately 60%, the 6-hour
      exposure by 70%, and the 24-hour exposure by more than 99%. The bactericidal
      activity was lowest with 0.125% bupivacaine and 2.0% mepivacaine. CONCLUSIONS:
      Antimicrobial activity was observed shortly after exposure of S. aureus to local
      anesthetics and appeared to be bactericidal rather than bacteriostatic. However,
      the observed bactericidal activity, although it developed rapidly, may be
      insufficient to account for the low incidence of epidural infection related to
      epidural cannulation.

PMID- 8744668
TI  - Nitric oxide synthesis inhibition enhances bupivacaine cardiotoxicity.
AB  - BACKGROUND AND OBJECTIVES: There is evidence that local anesthetic-induced
      seizures may be mediated by receptors for N-methyl-D-aspartate (NMDA) which
      activate production of nitric oxide (NO). The objective of this study was to
      determine the effects, if any, of inhibition of NO synthesis on the responses of
      the central nervous and cardiovascular systems to bupivacaine. METHODS: Sprague
      Dawley rats were assigned to two groups. The lightly anesthetized (0.5%
      halothane, 70% nitrous oxide) and paralyzed (doxacurium) animals were given N
      omega-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, 2
      mg/kg/min (n = 6) or saline (n = 5) intravenously for 30 minutes. Then
      bupivacaine was administered intravenously (2 mg/kg/min) to both groups of
      animals until asystole. Arterial blood samples for bupivacaine concentration
      analysis (by high-pressure liquid chromatography) were taken during the
      stabilization period and during local anesthetic infusion. Student's t-test was
      used to determine significant differences (P < .05) between groups. RESULTS:
      Average doses of bupivacaine that produced arrhythmias and asystole were
      remarkably lower in L-NAME-treated than in saline-treated rats (arrhythmia, 5.1
      +/- 2.0 vs 15.8 +/- 3.8 mg/kg; asystole, 15.9 +/- 3.2 vs 27.8 +/- 6.1 mg/kg; both
      P < .05). The doses producing seizures and isoelectric electroencephalograms and
      the duration of seizures did not differ significantly between the two treatment
      groups. However, electroencephalographic epileptiform activity was less intense
      (lower amplitude, shorter duration of ictal activity) in the L-NAME-treated
      animals. Arterial plasma concentrations of bupivacaine 5 minutes after the start
      of bupivacaine infusion were significantly higher in the L-NAME than in the
      saline group (22.3 +/- 2.9 vs 12.8 +/- 1.5 micrograms/mL, P < .05). CONCLUSIONS:
      These results suggest that NO synthase inhibition by L-NAME enhances the cardiac
      toxicity of bupivacaine, probably by a pharmacokinetic action, and reduces its
      central nervous system toxicity, probably by a pharmacodynamic action.

PMID- 8744669
TI  - Long-term use of subarachnoid clonidine for analgesia in refractory reflex
      sympathetic dystrophy. Case report.
AB  - BACKGROUND AND OBJECTIVES: A case is presented of intractable reflex sympathetic
      dystrophy resistant to all other types of treatment. METHODS: Twice daily
      subarachnoid clonidine was used to manage the symptoms via an implanted drug
      delivery system. RESULTS: The patient has successfully administered his own
      subarachnoid clonidine for over 18 months with no signs of tolerance or toxicity.
      CONCLUSIONS: Continuous subarachnoid clonidine may offer a solution to the
      management of some cases of intractable reflex sympathetic dystrophy.

PMID- 8744670
TI  - Cardiac arrest caused by coronary spasm in two patients during recovery from
      epidural anesthesia.
AB  - BACKGROUND AND OBJECTIVES: In order to reduce the surgical stress on the heart,
      anesthesiologists frequently use regional anesthesia in patients with coronary
      artery disease. METHODS: Two patients underwent reconstructive peripheral
      vascular surgery under continuous epidural anesthesia with bupivacaine. During
      the surgery and later in the recovery room, they received continuous
      electrocardiographic (ECG), invasive arterial blood pressure, and oxyhemoglobin
      saturation monitoring. RESULTS: In both patients, the anesthetic course during
      surgery was uneventful, but while recovering from the anesthesia, they developed
      ECG changes consistent with myocardial ischemia, followed by malignant
      dysrhythmias and cardiac arrest. The clinical pictures, ECGs, coronary angiogram,
      and (in one patient) autopsy findings suggested coronary artery spasm as the
      cause of the malignant dysrhythmias and cardiac arrests. CONCLUSIONS: It is
      possible that the coronary spasms were caused by an altered balance between
      sympathetic and parasympathetic nervous activity during recovery from epidural
      anesthesia. Therefore, patients with coronary artery disease must be closely
      monitored for signs and symptoms of myocardial ischemia during the entire
      recovery period from epidural anesthesia.

PMID- 8744671
TI  - Compartment block.

PMID- 8744672
TI  - Combined end-multiple lateral holes epidural catheter.

PMID- 8744673
TI  - Epidural hematoma after epidural pain control and concomitant postoperative
      anticoagulation.

PMID- 8744674
TI  - A simplified maneuver for transarterial approach to axillary block for use by a
      single anesthesiologist.

PMID- 8744675
TI  - The effect of preemptive fentanyl and halothane on formalin pain in mice.

PMID- 8744676
TI  - Comments on combined spinal-epidural anesthesia.

PMID- 8744677
TI  - HIV-1 prevention: interdisciplinary studies on the efficacy of bleach and
      development of prevention protocols.
AB  - In the United States, a major federally-funded approach to HIV-1 prevention for
      injecting drug users (IDUs) includes teaching them to always rinse their
      needles/syringes with household bleach and water before use. This report
      describes interdisciplinary studies of the extent to which HIV-1 can be found in
      injection equipment and the efficacy of bleach as a disinfectant, under simulated
      field conditions. Bloody needle/syringe units collected from Miami, Florida,
      shooting galleries or from community outreach prevention participants were
      selected for these studies. Groups of needle/syringe units were cleansed with
      bleach using a standard technique taught to IDUs in community outreach programs.
      Cleansed and uncleansed groups of needles/syringe units were then tested for the
      presence of HIV-1. The data demonstrate the efficacy of bleach rinses in reducing
      the risks of HIV-1 infection from needle/syringe units and indicate that the
      teaching of a bleach cleansing method to IDUs should be part of a total AIDS
      prevention protocol.

PMID- 8744678
TI  - Interleukin 10 inhibits interleukin 6 production and acute phase response in
      rheumatoid arthritis.
AB  - To evaluate the effect of interleukin 10 (IL-10) on acute phase response, we
      determined serum levels of IL-10, interleukin 6 (IL-6), C-reactive protein (CRP),
      alpha-1-acid glycoprotein (AGP), alpha-1-anti-chymotrypsin (ACT) in 34 rheumatoid
      arthritis (RA) patients. IL-10 and IL-6 levels were evaluated using an enzyme
      linked immunoassay (ELISA). CRP, AGP and ACT levels were measured using rocket
      immunoelectrophoresis. The results showed that IL-10 serum level was increased in
      RA patients as compared to controls (60.0 +/- 17.5 pg/ml vs. 7.2 +/- 1.9 pg/ml).
      IL-6 level was significantly elevated (87.3 +/- 32.7 pg/ml vs. 45 +/- 19 pg/ml, p
      < 0.05). CRP was significantly increased as compared to healthy controls (34 +/-
      19 mg/1 vs. 3 +/- 2 mg/1, p < 0.05). AGP and ACT serum levels were increased in
      RA patients, but we did not find these changes to be statistically significant. A
      good negative correlation between IL-10 and IL-6 serum level was found (r = 
      0.73, p < 0.05). A positive significant correlation between IL-6 serum level and
      CRP (r = 0.62, p < 0.05), AGP (r = 0.74, p < 0.05) and ACT (r = 0.45, p < 0.05)
      was established. Moreover, a negative correlation between IL-10 and serum level
      of CRP (r = -0.76, p < 0.05), AGP (r = -0.60, p < 0.05) and ACT (r = -0.37, p <
      0.05) was also shown. According to the data thus far obtained it seems that IL-10
      decreases IL-6 production, and by that indirectly affects acute phase response,
      decreasing CRP, AGP and ACT synthesis.

PMID- 8744679
TI  - Immunohistochemical comparative investigations of lymphatic tissue in reactive
      processes, myasthenic thymuses and Hodgkin's disease.
AB  - In this study coexpression of cytokeratin and desmin, and occasionally also Ki-1
      antigen, was displayed in extrafollicular reticulum cells of reactive lymph
      nodes. The absence or expression of trace amounts of these proteins in normal
      lymphoid tissue suggests that activation of T cell regions is correlated with the
      increased frequency of cytokeratin, desmin and Ki-1 expressing cells, and
      therefore may be a transient phenomenon. S-100-positive interdigitating reticular
      cells were found occasionally in extrafollicular T cell region of normal lymph
      nodes. They were, however, more numerous in reactive lymphatic tissue. In the
      myasthenic thymuses cells forming Hassall's corpuscles displayed coexpression of
      cytokeratin, desmin and Ki-1 antigen. Medullary epithelial cells were also
      cytokeratin-positive and, additionally, Ki-1 antigen was expressed on some cells
      dispersed in whole thymic tissue. S-100-positive interdigitating reticular cells
      were especially numerous in the thymic medulla and some of them found inside the
      Hassall's corpuscles. In Hodgkin's disease deficiency of cytokeratin and desmin
      in extrafollicular reticulum cells is a constant phenomenon in spite of a classic
      inflammatory background. However, Ki-1 antigen displayed Reed-Sternberg cells
      which, similar as some thymic cell elements, appear to originate from stromal
      perivascular mesenchyme. This fact suggests that Reed-Sternberg cells in
      Hodgkin's disease are pathologic counterparts of extrafollicular reticulum cells
      which represent a cellular differentiation defect to produce desmin and
      cytokeratin but with a possibility of Ki-1 antigen expression. The consequence of
      this may be the disregulation of immune system and the observed immunologic
      abnormalities. Further studies are needed to elucidate the role of Epstein-Barr
      viruses in this process. S-100-positive interdigitating reticular cells were in
      close contact with Reed-Sternberg cells and they were especially large and with
      numerous cells processes in the mixed cellularity (MC) subtype. The occurrence of
      interdigitating reticulum cells with S-100 protein expression, especially
      numerous in the T cell region activated of peripheral lymphatic tissue, as well
      as their close contact with Reed-Sternberg cells and with cells forming Hassall's
      corpuscles suggest their eventual possible role in the function of the immune
      system.

PMID- 8744680
TI  - Reactivity of monoclonal antibodies OK-CLL (anti-CD5) with peripheral blood cells
      of patients with B cell lymphoproliferative disorders.
AB  - Reactivity of OK-CLL monoclonal antibodies that can identify CD5 antigen on
      peripheral blood mononuclear cells, was investigated in 172 patients with B cell
      chronic lymphocytic leukemia (B-CLL) in clinical stages RAI O-I and RAI II-IV and
      in patients with non-Hodgkin's lymphomas, classified according to the Working
      formulation into high and low grade histologic type. The OK-CLL reactivity with B
      CLLs in the initial (RAI O-I), as well as in advanced stages of disease (RAI II
      IV) was significantly higher than in controls. Peripheral blood cells of lymphoma
      patients, regardless of histological type, showed a much lower values of the CD5
      positive population than chronic lymphocytic leukemia (CLL) patients, and a non
      significant discrepancy between the number of cells stained with anti-CD5 and
      those stained with other T cell markers. In spite of the showed considerable
      decrease of CD5 positive cells in CLL patients during therapy, elevated number of
      this population compared to normal individuals, after chemotherapy, was found.
      However, in lymphoma patients of both types of malignancies, CD5 positive
      population increased concomitantly with therapy. These results may suggest that
      analysis of CD5 antigen expression on peripheral blood cells of patients with B
      cell lymphoproliferative malignancies may have diagnostic, or, in correlation
      with some relevant clinical parameters, a potential predictive value in the
      treatment of those patients.

PMID- 8744681
TI  - Preactivation and phenotype of monocytes have no influence on their elimination
      from culture by activated T lymphocytes.
AB  - T lymphocytes can kill antigen-presenting cells (APC) in the presence of antigen
      or lectin. The subject of this study was to investigate whether the state of
      activation or phenotype of monocytes, influence their susceptibility to killing
      by T cells activated with pokeweed mitogen (PWM) or anti-CD3 monoclonal antibody.
      The data are presented which show that monocytes activation with cytokines (IFN
      gamma, IL-4, or IL-2), PPD, phorbol ester or phagocytic stimulus, have no
      influence on monocyte susceptibility to killing by T lymphocytes. Furthermore,
      flow cytometry data suggest that monocytes eliminated from culture have no
      characteristic phenotype. In conclusion, our data indicate that elimination of
      monocytes by activated T lymphocytes does not depend on the state of activation
      of monocytes.

PMID- 8744683
TI  - Influence of theophylline on interferon production and cAMP level Lpa cells.
AB  - In the presence and absence of methionine initiator tRNA (tRNA(iMet))
      theophylline applied for 1 h starting 6 h after induction increased significantly
      (2-fold) interferon (IFN) yield. Theophylline did not change the kinetics of IFN
      production in the presence of tRNA(iMet). The shut-off stage was present and the
      production was prolonged to 24 h after IFN induction. In comparison with the
      values obtained in untreated cells, poly I:C plus DEAE dextran (inducing complex)
      caused an about 2-2.5 fold increase of cyclic adenosine 3'5'-monophosphate (cAMP)
      level. The similar results were observed in the cells treated with inducing
      complex plus tRNA(iMet). About 2-fold higher cAMP level occurred in the cells
      under the influence of the inducing complex plus theophylline in comparison to
      the level obtained without theophylline. The addition of tRNA(iMet) did not
      influence the above presented data.

PMID- 8744682
TI  - Effect of peritoneal cells on tumors cells growth in vitro.
AB  - The cytotoxic and cytostatic activity of PMA-treated macrophages, obtained from
      pristane-primed BALB/c mice, was analyzed in vitro. The activated macrophages
      were cytotoxic and cytostatic for YAC-1 lymphoma, P-388 leukemia and P-815
      mastocytoma target cells. However, the RPC-5 plasmacytoma target cells appeared
      to be resistant to their cytotoxicity. The observed cytotoxic or cytostatic
      effects of macrophages in vitro were not correlated with their ability to produce
      the superoxide ion. Cytotoxic activity of NK cells, obtained from pristane-primed
      mice, was also studied. No differences in cytotoxicity of NK cells obtained from
      pristane-treated and untreated donors, were found. However, only the effector
      cells from untreated mice were able to respond to stimulatory effect of
      polyinosinic acid-polycytidylic acid-poly-L-lysine (poly ICLC).

PMID- 8744684
TI  - Effect of captopril and thiorphan on the proliferation of human neoplastic cell
      lines and their influence on cytostatic activity of interferon alpha or cytotoxic
      activity of doxorubicin.
AB  - We have assessed the effect of thiorphan or captopril on proliferation of two
      human tumor cell lines, A549 and HL60 including their influence on the cytostatic
      activity of interferon alpha or doxorubicin. The results showed that captopril
      inhibits the proliferation of both A549 and HL60 cells lines but thiorphan has
      antiproliferative effect only on A549 cells in a dose-dependent manner. However,
      neither captopril nor thiorphan administered in combination with interferon alpha
      or doxorubicin enhanced cytotoxic potential of doxorubicin and cytostatic
      activity of interferon alpha.

PMID- 8744685
TI  - Accumulation of inositol 1,4,5-triphosphate after cholinergic stimulation of
      human lymphocytes.
AB  - The interrelationships between the immune and neurohormonal system are the
      subject of this work. The formation of inositol 1,4,5-triphosphate (IP3) in
      response to cholinergic stimulation was studied in the human peripheral blood
      mononuclear cells (PBMC) and lymphocytes from the lymphoblastoid cell lines
      Jurkat and Raji. The cells were stimulated with mitogen and then treated with
      cholinergic agonist-carbachol or nicotine. The radioreceptor assay was used to
      determine the amount of IP3 in all studied lymphocytes. The results, combined
      with the presence of muscarinic and nicotinic receptors on the surface of these
      lymphocytes, suggest that the parasympathetic nervous system is involved in the
      immune-neurohormonal crosstalk.

PMID- 8744686
TI  - Influence of cyclosporine A on thyroid function in the experimental autoimmune
      thyroiditis (EAT) in mice.
AB  - We have examined the influence of cyclosporine A (CsA) on thyroid gland function
      during development of experimental autoimmune thyroiditis (EAT) in CBA (H-2k)
      mice, delivering the agent in different regimens and doses, either as commercial
      intravenous preparation or encapsulated into liposomes. The evaluation of
      autoimmunity was done by the assessment of serum concentration of thyroxine (T4).
      We showed that a high dose CsA (360 mg/kg) prevented the development of thyroid
      deficiency whereas a small dose (25-60 mg/kg) potentiated the decrease of T4
      serum level. Moreover, we found that the same dose of CsA enclosed in liposomes
      and of its commercial preparation can have different effect on T4 level in mice
      with EAT.

PMID- 8744687
TI  - Depression of interferon production in leukocytes of cows with fat mobilization
      syndrome.
AB  - White and Black dairy cows were classified on the basis of clinical symptoms,
      hematological data, biochemical tests of blood and histological examination into
      two groups: I--with fat mobilization syndrome (n = 11), II--healthy cows
      (control) (n = 6). Interferon (IFN) induction in leukocytes of cows with fatty
      liver, elevated ketone bodies, free fatty acids, bilirubin concentration and high
      aspartate aminotransferase (AST) activity, revealed impaired IFN production which
      was not improved by using known immunomodulators such as isoprinosine,
      levamisole, TFX and lactoferrin. The deficiency of IFN production observed in
      cows with fat mobilization syndrome may result in increased susceptibility of
      cows to different infections.

PMID- 8744688
TI  - Mechanism of antigenic variation in Shigella flexneri bacilli. III. Complement
      sensitivity of S. flexneri 1b strains and their 3b variants selected either as
      Lac+ recombinants or phage F2 resistant mutants.
AB  - Several S. flexneri 1b serotype strains of clinical isolation were compared with
      their 3b serotype variants isolated either as Lac+ recombinants from crosses of
      S. flexneri x E. coli Hfr C, or F2-resistant mutants. The studied variants 3b
      were deprived of type I antigen but acquired type III antigen. They appeared to
      be less sensitive to killing action of complement present in normal bovine serum
      although kinetics of killing and its effectiveness differed between the strains.

PMID- 8744689
TI  - Alterations in glycoconjugates related to the transformation grade of human
      uroepithelial cell lines.
AB  - To study the changes in carbohydrate expression associated with the progression
      of malignant phenotype, we have used the series of human urinary bladder
      epithelial cell lines. Non-tumorigenic and non-invasive cell lines, with infinite
      life span, were defined as transformation grade II (TGr II). Cell lines producing
      tumors in nude mice and invading fragments of embryonic chick hearts in vitro
      were defined as TGr III. In the present review the results obtained from our
      immunochemical, biochemical and structural studies on glycosphingolipids and
      glycoproteins of 10 human urothelial cell lines representing both grades of
      transformation are summarized and discussed in relation to the literature data.
      TGr III cell lines are characterized by decreased level of the GM2 ganglioside,
      presence of sialyl-Le(a) ganglioside, increased amount of more highly branched,
      tri- and tetraantennary N-acetyllactosamine-type glycans and higher number of
      binding sites for peanut lectin and wheat germ agglutinin lectin, as compared to
      non-tumorigenic and non-invasive TGr II cell lines.

PMID- 8744690
TI  - Mouse monoclonal IgA antibodies lack interchain disulfide bonds.
AB  - A mouse monoclonal IgA antibody (A008), anti-blood group A antigen, was shown to
      dissociate into heavy (H) and light (L) polypeptide chains under non-reducing
      conditions. The dissociation occurred in the presence of 0.2% sodium dodecyl
      sulphate (2 h at room temperature) or at elevated temperature (1 h at 70 degrees
      C). The free H and L polypeptide chains could be separated in SDS-polyacrylamide
      gel electrophoresis or by gel filtration in the presence of SDS. The dissociation
      of IgA (A008) antibody into heavy and light polypeptide chains was reversible,
      since the fractions containing gel filtration-isolated chains, after removing the
      detergent, pooling together and incubation at 4 degrees C created again the
      immunoglobulin molecules with activity close to the native value. Similarly, the
      same IgA antibody heated at 70 degrees C for 1 h recovered its antibody activity
      after keeping at 4 degrees C. Three other mouse monoclonal IgA antibodies showed
      the same ability to dissociate into heavy and light polypeptide chains after
      exposure to SDS or elevated temperature, which suggests that this outstanding
      property is a characteristic feature of the mouse monoclonal IgA antibodies and
      it comes out from the lack of H-H, L-L and H-L interchain disulfide bonds in
      these molecules.

PMID- 8744691
TI  - Human serum immunoglobulins binding to synthetic fragments of human chorionic
      gonadotropin.
AB  - Human sera obtained from healthy individuals, patients with cancer diseases,
      infertile and pregnant women were investigated for the presence of
      immunoglobulins (Ig) binding to synthetic fragments corresponding to sequence of
      human chorionic gonadotropin (hCG). Four synthetic peptides corresponding to some
      regions of alpha hCG and beta hCG subunits, coupled to polystyrene beads and 16
      peptides overlapping sequences of alpha- and beta hCG subunits, synthesized on
      polyethylene pins, were used. IgG and IgM bound to hCG-synthetic peptides were
      assayed using goat or mouse monoclonal antibodies anti-human IgG labeled with
      horseradish peroxidase. Most of the investigated sera contained IgG which bound
      to examined synthetic peptides, but obtained results were dependent on serum
      donors. Some relationships between results obtained with peptides synthesized on
      modified pins according to Geysen et al. method and corresponding peptides
      synthesized by Merrifield method and coupled to beads were noted.

PMID- 8744692
TI  - Stability of human lutropin studied with immunoenzymatic technique.
AB  - Characteristics of two monoclonal antibodies against human lutropin and their use
      in enzyme immunoassays of the hormone are presented. Diluted solution of
      pituitary lutropin was unstable in buffered saline and could be stabilized with
      some proteins. Concentration of the lutropin in woman urine, collected during
      "lutropin-peak", was markedly increased during long time storage at 5 degrees C
      or at room temperature. Using HPLC it was demonstrated that pituitary lutropin,
      normal urine lutropin and "increased" urinary lutropin were eluted from ion
      exchange column almost with the same retention time.

PMID- 8744693
TI  - Comparison of the influence of stress exercise test and transesophageal cardiac
      pacing on polymorphonuclear neutrophils functions.
AB  - Peripheral polymorphonuclear neutrophils (PMN) number, percent of PMN bearing IgG
      Fc receptors as well as PMN adherence were evaluated in 29 patients submitted to
      an exercise test. The peripheral PMN count significantly increased at the maximal
      work load. The increase in number of neutrophils bearing IgG Fc receptors was
      also noticed at that point, while PMN adherence to nylon wool columns did not
      change significantly. Nine subjects were additionally submitted to diagnostic
      transesophageal atrial pacing with a rate similar to maximal heart rate observed
      during the exercise test. It was revealed that atrial pacing in these patients
      had no influence on the peripheral PMN count, PMN adherence as well as number of
      neutrophils bearing IgG Fc receptors. We conclude, that granulocytosis observed
      during exercise can not be solely attributed to the increased heart rate and
      increased cardiac output but other mechanisms like muscle work play a significant
      role in this process.

PMID- 8744694
TI  - Autologous peripheral blood stem and progenitor cells transplantation as a valid
      treatment approach in recurrent, refractory lymphoma.
AB  - Autologous peripheral blood stem cell transplantation (APBSCT) is used similarly
      to autologous bone marrow transplantation (ABMT) to reconstitute bone marrow
      following myeloablative therapy in patients with proliferative diseases of the
      blood. Eight patients with recurrent and refractory lymphoma (3 HD, 4 NHL) and
      multiple myeloma aged 17-55 were included into the study. Peripheral blood stem
      cells following their prior mobilisation with cyclophosphamide 4-7 g/m2 and/or G
      CFS or Dexa-BEAM + G-CSF were collected by subsequent leukaphereses on Fenwal
      CS3000. Nucleated cells were separated by sedimentation, cryopreserved in a
      programmed freezer and then stored at-196 degrees C. Bone marrow has been
      additionally collected in one patient. Conditioning treatment prior to
      transplantation consisted of BCNU, etoposide and cyclophosphamide (CBV) in
      lymphomas and melphalan in multiple myeloma. Collected material with mean
      cellularity 5.52 x 10(8)/kg and mean CD34+ contents 6.27 x 10(6)/kg was reinfused
      by central line. G-CSF was given in 5 patients to hasten the bone marrow
      recovery. All patients fully recovered and left hospital on average 35.5 days
      following transplantation. No signs of relapse were seen throughout the
      observation period (mean 349.5 days). Neutrophils > 0.5 G/1 were obtained on day
      + 20, > 1.0 G/1 on day 30, platelets > 50 G/1 on day 29, > 100 G/1 on day 53,
      reticulocytes > 0.015 on day 30, erythrocytes transfusions were needed up to day
      39. Presented outcomes together with other reports indicate, that APBSCT is a
      highly efficient way to rescue repeatedly relapsing patients with proliferative
      diseases of the lymphatic systems, even those presenting with changes in the bone
      marrow (neoplasmatic infiltrate, hypoplasia or fibrosis).

PMID- 8744695
TI  - Influence of gold salts treatment on the serum concentration of IL-1 and IL-2 in
      patients with rheumatoid arthritis.
AB  - Eighteen subjects (2 males, 16 females) with rheumatoid arthritis were treated
      with gold salts for 6 months. The statistically significant decrease of IL-1 and
      IL-2 levels during the treatment was observed. The mean serum concentrations of
      IL-1 and IL-2 decreased from 41.0 +/- 11.5 to 28.6 +/- 7.3 (p < 0.001) and 98.3
      +/- 57.6 to 29.3 +/- 20.5 fmol/ml (p < 0.001), respectively. This decrease was
      accompanied by a decline of serum concentration of acute phase proteins and
      immunoglobulins. These results can explain a strong anti-inflammatory action of
      gold salts in patients with rheumatoid arthritis.

PMID- 8744696
TI  - Synthesis and immunological activity of mono- and disubstituted derivatives of
      2,5-dimercapto-1,3,4-thiodiazoles.
AB  - It is presented that the newly synthesized mono- and disubstituted 2,5-dimercapto
      1,3,4-thiodiazole derivatives exert immunotropic activity. This effect was
      evaluated by measuring plaque forming cell number, circulating immunoglobulins
      level, autologous rosette number, mitogenic activity and by performing popliteal
      lymph node assay. It is shown that intensity of immunotropic activity depends on
      chemical structure: mono-substituted derivatives had a strong suppressive effect,
      disubstituted compounds showed the variable activity. One compound of this group
      exerted a stimulatory effect. The tested compounds were active in popliteal lymph
      node assay and had no mitogenic activity.

PMID- 8744697
TI  - Lactoferrin lowers the incidence of positive Coombs' test in New Zealand black
      mice.
AB  - The results presented in this communication show that New Zealand Black (NZB)
      mice treated for a prolonged period with bovine lactoferrin (BLF) exhibit a
      decreased frequency of positive Coombs' reaction. This effect was dose dependent
      and best pronounced at a dose of 50 micrograms/dose. We found, in addition, that
      incubation of peritoneal cells with BLF resulted in a decreased number of cells
      recognizing Hb antigen on autologous erythrocytes. The data indicated that
      lactoferrin may be of therapeutical value in treatment of autoimmune disorders.

PMID- 8744698
TI  - Influence of Lys-residue deletion on the immunomodulatory activity of peptides
      related to immunosuppressive region of lactoferrin.
AB  - The effects of Lys residue deletion from peptides, related to immunosuppressive
      regions of lactoferrin (LF), were studied in the humoral and cellular immune
      responses to sheep erythrocytes (SRBC) in mice. We found that the deletion of Lys
      residue, vicinal to Pro, influences mostly the immunomodulatory activity of short
      fragments (tetra-, and pentapeptides) of immunosuppressive 231-245 mini-domain of
      LF. The activity of longer peptides, related to this mini-domain, is influenced
      to much lower extent by Lys removal. In particular, the tetrapeptide derived from
      Arg-Lys-Pro-Val-Asp sequence by deletion of Lys, exhibits strongly reduced
      immunosuppressive activity. On the contrary, the similar change within Arg-Lys
      Pro-Val-Thr sequence, derived of 575-589 loop of LF, produces a tetrapeptide Arg
      Pro-Val-Thr, that is active as immunosuppressor both in humoral and cellular
      immune response. A quite strong immunosuppressive activity of tripeptide Lys-Arg
      Pro is also worth consideration, especially when compared with the loss of
      activity observed for Thr-Arg-Pro tripeptide. The data presented herein indicate
      that exclusion of Lys residue from the LF-derived immunomodulatory peptides
      differentially alters their effects on the immune response to SRBC in mice.

PMID- 8744699
TI  - Lymphocyte mitogen-induced proliferation in patients with allergic rhinitis.
AB  - Lymphocytes play a central regulatory role in mechanisms contributing to impaired
      function of immune system in atopy. The aim of our study was evaluate the mitogen
      induced proliferation of lymphocytes in a group of asymptomatic, seasonal
      allergic rhinitis patients. A highly significant lower mitogen-induced
      proliferation and, in contrast to other studies, significantly lower background
      proliferative activity of lymphocytes were found in the atopic persons, comparing
      to the controls. We concluded that the decreased mitogen-induced proliferation of
      lymphocytes observed in allergic patients reflects abnormal T cell function,
      which is due to the atopic status, and not only as it was believed to the antigen
      induced lymphocyte activation.

PMID- 8744700
TI  - Effect of domperidone-induced hyperprolactinemia on selected immune parameters in
      healthy women.
AB  - Domperidone, anti-emetic drug, given to healthy female volunteers, induced an
      elevation of plasma prolactin (PRL) concentration with the peak in 1-4 h. The
      release of prolactin had a transient stimulating effect on theophylline sensitive
      T lymphocytes and on concanavalin A induced mitogenic activity, suggesting an
      enhanced activity of T suppressor lymphocytes. The relative number of CD4+
      lymphocytes decreased markedly one hour after domperidone administration and
      returned to normal values within 2 h (that means 3 h after taking the drug). The
      number of lymphocytes positive for dipeptidyl peptidase IV exhibited similar
      transient increase and normalization of activity. No change was observed in the
      number of CD8+ lymphocytes. The production of interferon by leukocytes treated
      with Newcastle disease virus was found to be significantly increased 2 h after
      domperidone administration. The results suggest that prolactin can selectively
      stimulate some functions of cellular immunity as well as the release of cytokines
      (IFN). The present study may contribute to the understanding of the role of the
      immune system in endogenous hyperprolactinemia.

PMID- 8744701
TI  - Cell migration between graft and host--an analysis with monoclonal antibodies
      after allogeneic rat kidney transplantation.
AB  - In order to analyse migration patterns of donor MHC class II cells out of
      transplanted kidney and accumulation of host cells within the graft,
      immunomorphological studies were performed using monoclonal antibodies in rat
      allogeneic kidney transplantation model. To answer the question of how many donor
      cells migrate out of the renal cortex MRC 0 x 3 monoclonal antibody (MoAb)
      against LEW MHC class II antigens was used. In the grafts explanted after 4,24 48
      and 73 h, a slow reduction of donor class II cells was observed and some areas in
      cortex showed only very few, if any, donor cells. At the same time, starting from
      day 2 after transplantation accumulation of donor cells was found in perivascular
      spaces. Spleen sections stained at 24, 48, 72 and 96 h after transplantation
      revealed donor cells present in recipient's spleen. They were detected up to day
      3 after surgery. Their numbers, however, decreased after day 2. After 2 and 3
      days, accumulations of recipient's cells between tubules were detected. It was
      found that many cells in infiltrations were stained with anti-T lymphocyte MoAb.
      Expression of class II antigen on rat kidney cells increases significantly from
      the day 4 after transplantation.

PMID- 8744702
TI  - Four new cytotypes of the onchocerciasis vector blackfly Simulium guianense in
      Brazil.
AB  - Simulium (Trichodagmia) guianense is an important Amazonian vector of
      onchocerciasis. Examination of the polytene chromosome banding patterns of larvae
      from five sites in Brazil revealed the occurrence of four cytotypes, designated
      A, B, C and D. The chromosomal standard, Simulium guianense A, occurred at two
      localities in Goias State (on the Rio Tocantins and Rio Mucambao) where it was
      the only cytotype. The other three sites examined yielded one different cytotype
      from each: B from Rio Oyapoque in Amapa State, C from Rio Tocantins in Maranhao
      State, and D from Rio Xingu in Para State. All cytotypes differed by at least two
      fixed inversions, but a sex determining system was not evident in any cytotype.
      As the cytotypes have been found allopatrically it is not certain that they
      represent sibling species; sampling of sympatric populations would resolve this.
      During certain times of the year, voracious anthropophagy by S.guianense sensu
      lato occurs at the localities sampled for cytotypes A, C and D (biting data are
      not available for the cytotype B locality). In some other areas, however,
      S.guianense s.l. is entirely zoophilic. Further studies are needed, therefore, to
      elucidate the biting habits, vectorial capacity, geographic distribution and
      taxonomic status of these four, and perhaps additional, cytotypes comprising the
      S.guianense complex.

PMID- 8744703
TI  - The effect of host nutrition on itch mite, Psorergates ovis, populations and
      fleece derangement in sheep.
AB  - A group of thirty-two Merino sheep infested with itch mites (Psorergates ovis)
      and fed a maintenance diet which imposed moderate nutritional stress had a
      significantly higher mite population, significantly more skin scurf, and
      significantly more fleece damage or derangement (P < 0.05) than a second group of
      thirty-two infested sheep fed a diet designed for unrestricted body weight gain
      and wool growth. Histologically there were no significant differences between the
      groups in the numbers of mast cells, neutrophils or eosinophils observed in skin
      sections, but sheep that had high mite counts ( > 10 per 200 cm2 of skin area) in
      both groups, had more dermal mast cells than sheep with fewer mites irrespective
      of the plane of nutrition. Skin thickness and greasy fleece weight in the group
      maintained on the low plane of nutrition were significantly less (P < 0.05) than
      in the well-nourished group, reflecting the difference in protein and energy
      content of the two diets. Within the nutritionally stressed group, the sheep with
      low mite counts had a significantly lower (P < 0.05) greasy fleece weight and a
      shorter mean staple length than the sheep with high mite counts. There was no
      significant difference in greasy fleece weight between sheep with low or high
      mite counts in the group fed on the high plane of nutrition.

PMID- 8744704
TI  - The effects of selection for size in cattle on horn fly population density.
AB  - Statistically significant differences were observed in the population density of
      the horn fly, Haematobia irritans irritans L., on Angus cows having significantly
      different frame sizes. Angus cows, averaging < 112.5 cm in height at the hip, had
      significantly lower numbers of horn flies than Angus cows that measured 112.5
      117.5 cm, 117.5-120 cm, 120-126 cm and > 126 cm in height at the hip. The Angus I
      cows ( < 112.5 cm in height at the hip) were significantly shorter in length
      (mean distance from the withers to the hip bone) and were smaller in girth than
      the Angus II (112.5-126 cm) and Booneville Angus cows ( > 126 cm). The estimated
      heritability (h2) of horn fly resistance was 0.43 +/- 0.07 and 0.95 +/- 0.31 for
      1989 and 1990, respectively. Horn fly counts on the Angus I herd ( < 112.5 cm in
      height) was 118.1 (probable breeding value, PBV = -20.69) to 165 horn flies per
      cow (PBV = 26.9 flies per cow in 1989) and from 75.9 (PBV = -29.1) to 134.5 (PBV
      = 29.5) flies per cow in 1990. Angus I bulls had PBV = -23.7 to 13.4 and from 
      26.5 to 14.75 in 1989 and 1990, respectively. The Angus II cows had horn fly
      counts that ranged from 159.6 (PBV of -23.5) to 208.1 (PBV of 25) per cow in 1989
      and from 232.3 (PBV of -56.2) to 378.7 (PBV of 90) per cow in 1990. Angus II
      bulls had PBVs that ranged from -17.1 to 18.9 in 1989 and from -28.1 to 48.8 in
      1990. The Angus I cows had significantly (P < 0.0001) lower numbers of horn flies
      (mean of 63.8 horn flies per m2) than the small, medium or large Angus II cows
      (mean of 129.4, 149.6 and 145.5 horn flies per m2, respectively). The data
      indicated that some specific factor(s) associated with cow size contribute(s) to
      innate resistance of cattle to the horn fly.

PMID- 8744705
TI  - Effect of weather conditions on the flight activity of Nigerian blackflies
      (Diptera:Simuliidae).
AB  - A vehicle-mounted net was used to make hourly catches of blackflies at 700-1000 m
      altitude in the River Assob valley, central Nigeria, on 20 days during the dry
      season. Pearson Correlation Matrix analysis of the collection data and
      meteorology showed that the main factors affecting flight activity of each of the
      four most abundant blackfly species were primarily light intensity and secondly
      wind velocity, whereas relative humidity was the least important factor. Flight
      activity showed a negative linear regression against wind, with some activity
      occurring in wind speeds up to 15 km/h. Distance-weighted least-squares (DWLS)
      regressions showed little correlation of temperature with activity for Simulium
      hargreavesi and S.adersi, but S.squamosum and S.vorax had small peaks at 28
      degrees C and 31 degrees C, respectively. DWLS regression against light intensity
      showed an activity peak at 6000 lux, except in Simulium adersi.

PMID- 8744706
TI  - Permethrin-impregnated bednets are more effective than DDT house-spraying to
      control malaria in Solomon Islands.
AB  - A field trial compared DDT house-spraying with permethrin-impregnated bednets for
      malaria control in Solomon Islands from 1987 to 1991. Mortality-rates of malaria
      vector Anopheles farauti in exit window traps were 11.6% from an untreated hut,
      10.1% from a hut sprayed with DDT 2 g/m2, and 98% of those from a hut in which
      the occupants used bednets treated with permethrin 0.5 g/m2. Since bioassays of
      the DDT-sprayed walls (15 min exposure in W.H.O. standard test cones) gave 77%
      mortality of An.farauti, it was concluded that the insignificant impact of DDT
      could be explained by the exophilic behaviour of endophagic vectors, whereas the
      greater impact of permethrin was attributed to the more effective exposure of
      An.farauti females to the impregnated bednets-attracted by the occupants. The
      parous rate was higher indoors, except in the area with permethrin-impregnated
      bednets. It was therefore concluded that permethrin-impregnated bednets reduced
      the mean longevity of An.farauti and hence its vectorial capacity. The
      circumsporozoite (CS) antigen positivity rate of An.farauti in the DDT area was
      0.18% outdoors, significantly less than 1.42% indoors. In the comparison area CS
      rates were 0.65% outdoors and 0.75% indoors. CS antigen was not detected in
      An.farauti from the bednet area, indicating the apparent prevention of malaria
      transmission. As DDT spraying was so much less effective, it was discontinued in
      1993 and permethrin-impregnated bednets are now the principal malaria control
      method in Solomon Islands.

PMID- 8744707
TI  - A self-medicating applicator for control of ticks on deer.
AB  - A self-medicating applicator for killing ticks on deer and domestic ungulates by
      passive transfer of acaricides during feeding is described. The applicator
      consists of a barrel divided into a food bin (above) and a sealed self-contained
      acaricide reservoir (below) with a vertical, centrally-located ceramic column
      that extends from the reservoir into the food bin. Acaricide is drawn up the
      column from the sealed reservoir by absorption. Animals attracted to the food in
      the device acquire the acaricide during feeding when they contact the uppermost
      portion of the column. White-tailed deer (Odocoileus virginianus) readily utilize
      the applicator in penned and natural conditions. In a field study, examination of
      hunter-killed deer demonstrated that animals from a treated site were infested
      with many fewer Ixodes scapularis (3.4 +/- 1.1) than those from a control site
      (10.8 +/- 3.0). Chromatographic analysis of hair samples revealed traces of
      permethrin on three of the four animals examined, suggesting use of applicators
      by these deer. In a study using penned goats (Capra hircus) infested with
      Amblyomma americanum ticks, treatment efficacy reached 86.4% within 4 days of
      exposure to the applicators. Visual observations confirmed that all animals used
      the applicators. Gas chromatographic analysis of goat hair samples indicated that
      permethrin was detectable on all of the treated animals exposed to the device.

PMID- 8744708
TI  - Surveillance of the mosquito Aedes aegypti and its biocontrol with the copepod
      Mesocyclops aspericornis in Australian wells and gold mines.
AB  - A survey of the dengue vector mosquito Aedes aegypti was undertaken using funnel
      traps to detect immature stages (larvae and pupae) in flooded disused mine shafts
      and wells in Charters Towers, Queensland, Northern Australia. The town has a
      history of dengue fever since 1885 when goldminers were the first recorded
      victims. During the latest dengue epidemic in 1993, 2% of the population had
      laboratory-confirmed dengue virus Type 2, despite source reduction of Ae.aegypti
      breeding-sites at ground level or above. This led to suspicions that dengue
      vector Ae.aegypti breeding-sites might be below ground level. When surveyed in
      March 1994, Ae.aegypti immatures were found in 9/10 wells and 1/6 mine shafts.
      The water in wells and mines had similar characteristics-except that turbidity
      was higher in the mines, which more often contained predators of mosquito
      immatures. The copepod Mesocyclops aspericornis was collected from water in 1/10
      wells and 2/6 mine shafts. Laboratory predation trials resulted in 95.5-100%
      predation by 25 copepods/l on Ae.aegypti first-instar larvae up to 200 larvae/l.
      Five wells containing Ae.aegypti in the survey were inoculated with fifty
      indigenous M.aspericornis, and five wells (one positive and four negative in the
      survey) were left untreated as controls. Nine months later, in December 1994,
      Ae.aegypti had been eliminated from all five treated wells but all untreated
      control wells contained Ae.aegypti, except for one well that contained a natural
      population of M.aspericornis. The role of wells and mines as winter/ dry season
      refuges of Ae.aegypti in northern Australia is reviewed, and we recommend the use
      of M.aspericornis as a cost-effective, environmentally acceptable and persistent
      agent for the sustainable control of Ae.aegypti, especially in inaccessible
      breeding sites.

PMID- 8744709
TI  - Mitochondrial DNA variation in screwworm.
AB  - Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      analysis was used to characterize mitochondrial DNA (mtDNA) variation in
      screwworms, Cochliomyia hominivorax, and secondary screwworm, C.macellaria, from
      the Caribbean, North America and South America. Four amplicons, totaling 7.1 kb,
      were analysed with sixteen restriction enzymes. A total of 133 restriction sites
      was observed in the two species, 104 in C.hominivorax, of which nineteen were
      variable, and ninety-five in C.macellaria, none of which was variable. Fourteen
      mtDNA haplotypes were observed among eighteen C.hominivorax examined. Mean
      divergence between C.hominivorax haplotypes (d) was 0.0064 substitutions per base
      pair and genotypic diversity (G) was 0.97. Mean divergence between C.hominivorax
      and C.macellaria was 0.0824. Cochliomyia hominivorax haplotypes could be divided
      into three assemblages representing North America, South America and Jamaica,
      based on UPGMA clustering with d values. The assemblages did not exhibit complete
      geographic fidelity. These data were discordant with previously published
      allozyme data indicating little differentiation between screwworm populations. A
      scenario invoking historically isolated populations coming into contact with the
      introduction and movement of European livestock is proposed to explain the
      observed population structure of screwworm.

PMID- 8744710
TI  - The relationship between female body size and survival rate of the malaria vector
      Anopheles arabiensis in Ethiopia.
AB  - The relationship between female mosquito body size and survival rate was studied
      in field populations of Anopheles arabiensis in the Awash valley, central
      Ethiopia. Body size was quantified by measuring the wing-length. Highly
      significant correlations were found between size, parousness and insemination. It
      was concluded that larger An.arabiensis females have a higher probability of
      survival, being inseminated and producing more egg batches than smaller adults.
      Implications for vectorial capacity and vector competence of mosquitoes are
      discussed.

PMID- 8744711
TI  - Genetic variation in populations of Culicoides variipennis complex in the six New
      England states, U.S.A.
AB  - We investigated the identity and distribution of members of the Culicoides
      variipennis complex in the six New England states of the U.S.A., a region where
      bluetongue transmission has not been detected. Analyses of seven polymorphic
      isozyme-encoding loci showed that only C.v.variipennis, not considered to be a
      vector of the bluetongue viruses, was present. The populations of C.v.variipennis
      were significantly more hetero-zygous than C.v.sonorensis and C.v.occidentalis
      populations from similar studies in the state of California. Estimates of genetic
      diversity among populations of C.v.variipennis in New England were similar to
      C.v.sonorensis in the state of Colorado, but were significantly more genetically
      divergent than California populations of C.v.occidentalis. The impact of these
      findings on the status of New England as a possible bluetongue-free region for
      the purpose of international trade in ruminant livestock and their germplasm is
      discussed.

PMID- 8744712
TI  - Seasonal variation of Leishmania major infection rates in sandflies from rodent
      burrows in Isfahan province, Iran.
AB  - In preparation for field trials of killed Leishmania major vaccine, natural
      infections with Leishmania promastigotes were monitored in Phlebotomine sandfly
      vectors from villages of Borkhar rural district, northeast of Isfahan in central
      Iran, where L.major zymodeme MON-26 ( = LON-1) has been identified as causing
      zoonotic cutaneous leishmaniasis (ZCL). Sandflies were collected and dissected
      weekly, from burrows of rodent colonies, during the "sandfly season', June
      October 1991. Leptomonad infection rates were 12% of 26 Phlebotomus ansarii, 8%
      of 280 P.caucasicus, 11% of 1042 P.papatasi and none of 126 Sergentomyia sintoni,
      being greatest during late August through September, coinciding with peak
      activity of the sandflies, 2-3 months before the highest incidence of ZCL human
      cases in November-December.

PMID- 8744713
TI  - Atmospheric transport of mosquitoes in northeast India.

PMID- 8744714
TI  - Transmission of Heterotylenchus autumnalis nematodes into field populations of
      Musca autumnalis by release of laboratory-reared specimens.

PMID- 8744715
TI  - Morphological differentiation of adult females of the Simulium damnosum complex
      from Nigeria.

PMID- 8744716
TI  - Mites infesting phlebotomine sandflies in southern Sinai, Egypt.

PMID- 8744717
TI  - Perennial transmission of malaria by the Anopheles gambiae complex in a north
      Sudan Savanna area of Mali.

PMID- 8744718
TI  - Vector competence of the Simulium damnosum complex in Cameroon for Onchocerca
      spp. from cattle.

PMID- 8744719
TI  - Incidence of bone marrow transplantation in Europe. Report from the European
      Group for Blood and Marrow Transplantation.
AB  - The European Group of Blood and Marrow Transplantation (EBMT) is collecting
      information on incidence of bone marrow transplantation in Europe. 203 teams in
      26 European countries performed in 1992 a total of 6065 bone marrow transplants
      (BMT). There were 2666 (44%) allogeneic transplants from 2171 HLA identical
      sibling donors, 170 non-identical family donors, 29 twin donors and 296 unrelated
      volunteer donors. There were 3399 autologous transplants (56%): 2494 autologous
      BMT, 644 autologous peripheral blood stem cell transplants and 261 combined
      autologous bone marrow peripheral blood stem cell transplants. Transplant
      indications were leukemias in 2963 patients (49%) (1987 allogeneic, 976
      autologous), lymphoproliferative disorders in 1890 patients (31%) (201
      allogeneic, 1689 autologous), solid tumors in 739 patients (12%) (10 allogeneic,
      739 autologous), aplastic anemia in 194 patients (3%) (193 allogeneic, 1
      autologous), thalassemia in 128 patients (2%) (all allogeneic), inborn errors in
      115 patients (2%) (all allogeneic) and miscellaneous disorders in 36 patients (32
      allogeneic, 4 autologous). Main differences were observed in the number of
      transplanting teams, and in the number of allogeneic and autologous transplants
      performed in the different European countries compared to the number of
      inhabitants.

PMID- 8744720
TI  - HLA and bone marrow transplantation.
AB  - Bone marrow transplantation between HLA-identical siblings is an established
      therapeutic strategy in leukemia and a variety of lympho-hematopoietic disorders.
      In recent years unrelated donors were increasingly used for patients lacking a
      family donor. Here we report on current progress in HLA class II typing by
      molecular methods which have influenced donor search and improved matching.

PMID- 8744721
TI  - DRB polymerase chain reaction fingerprinting, DQA oligotyping and mixed
      lymphocyte culture results in related bone marrow donors and recipients.
AB  - Donor and recipient are usually regarded as well matched for bone marrow
      transplantation when they are compatible in HLA class I and II antigens and in
      mixed lymphocyte culture (MLC). However, results of serological typing of class
      II antigens may be unreliable. Hence, polymerase chain reaction fingerprinting of
      HLA DRB (PCR FP) was introduced for the screening of related donors for 29
      patients awaiting bone marrow transplantation. In addition, the sequence-specific
      oligonucleotide (SSO) typing of DQA alleles was performed. In 18 pairs the
      results of DNA analysis methods were compared with the results of MLC. 72% of
      pairs were HLA DQA compatible and 59% showed compatibility in PCR FP. MLC
      compatibility was found in 61%. A higher correlation of PCR FP and MLC results
      was observed.

PMID- 8744722
TI  - Analysis of reconstituting T cell receptor repertoires in bone marrow transplant
      recipients.
AB  - Allogeneic bone marrow transplantation (BMT) has become the treatment of choice
      for a variety of hematopoietic disorders. An important factor limiting the use of
      allogeneic BMT is delayed restoration of immune function. A quantitative
      understanding of immune reconstitution of the T cell compartment based on an
      efficient method of analysis would be of benefit. Distinct lineages of T cells
      which have resulted from previous and ongoing clonal expansion can be identified
      by their unique T cell receptors (TCR). Thus, TCR complexity can be used as a
      measure of repertoire complexity. Here we use a polymerase chain reaction-based
      approach which visualizes the size heterogeneity of the third complementarity
      determining region (CDR3) to study T cell reconstitution in adult bone marrow
      transplant recipients. We find that repertoire complexity, as determined by the
      number of bands of different length for each V family, reflects the general
      immune status of individuals tested. Contractions and gaps in repertoires are
      revealed in individuals suffering from recurrent infections associated with T
      cell impairment. This approach provides a new tool in the analysis of
      reconstitution of alpha/beta T cell repertoires and it can be also be applied to
      B cells and gamma/delta T cells.

PMID- 8744723
TI  - Cytokines, adhesion molecules (E-selectin and VCAM-1) and graft-versus-host
      disease.
AB  - Analysis of skin biopsy specimens for the presence of adhesion molecules,
      composition of cellular infiltrates, Ki-67 antigen expression, and examination of
      serum for interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha)
      levels, wes performed in patients after allogeneic bone marrow transplantation
      (alloBMT), to study the pathomechanism of acute graft-versus-host disease
      (aGvHD). It was found that: 1) early hematological recovery constitutes a risk
      factor for grade IV GvHD, 2) vascular cell adhesion molecule-1 (VCAM-1) is
      present in the matrix organizing the cells in the bone marrow and in aGvHD
      infiltrates, 3) HLA DR antigens aberrant expression in epithelial cells, as well
      as 4) strong expression of Ki-67 is seen in early stages of aGvHD. These
      immunopathomorfological lesions are cytokine-dependent. High levels of IL-6 and
      TNF-alpha were found in sera of patients affected with the aGvHD process and
      infectious complications. An increase of IL-6 in the course of aGvHD is a sign of
      poor prognosis. These data support the notion that cytokines facilitate the cell
      accumulation at the site of aGvHD at the beginning of this process and again, at
      the final stage of the disease, cytokines high levels are associated with the
      organ damage.

PMID- 8744724
TI  - Statistical evaluation of bone marrow transplantation data.
AB  - The analysis of data generated from a transplant programme is fundamental to
      assessing both the effectiveness of different treatments, and the prognostic role
      of disease and patient variables. Therefore, the use of life-table analyses,
      methods of comparing survival curves, and a brief discussion of multivariate
      methods, will be presented.

PMID- 8744725
TI  - Use of spontaneously mutated human DNA as competitive internal standard for
      nucleic acid quantification by reverse transcription-polymerase chain reaction
      (RT-PCR).
AB  - Quantification of gene expression is of increasing interest in many medical
      sciences. Methods based on reverse transcription-polymerase chain reactions (RT
      PCRs) are timesaving and require only very small amounts of RNA. A limiting
      factor, however, is the significant fluctuation in the efficacy of reverse
      transcription as well as in the polymerase chain reactions. Various external and
      internal standards have been suggested for correcting these fluctuations. We
      describe a novel way of creating an internal standard for assessing the
      expression of type VII collagen in human cells. The total RNA of a patient with
      hereditary epidermolysis bullosa dystrophica associated with a homozygous T to A
      point mutation in type VII collagen gene was reverse transcribed and a 382bp
      fragment of type VII collagen cDNA containing the mutation was amplified. The
      mutated cDNA, unlike normal type VII collagen cDNA could be cleaved by EarI
      endonuclease into 244bp and 138bp fragments. Semiquantitative PCR was performed
      with the mutated cDNA as internal standard and the studied cDNA sample in the
      same tube in the presence of alpha 32P-labeled dCTP. The reaction was followed by
      EarI digestion, electrophoresis on a polyacrylamide gel and exposure to a X-ray
      film. In conclusion, we describe a timesaving method for creating internal
      standards for semiquantitative RT-PCR.

PMID- 8744726
TI  - Cell proliferation-associated nuclear antigen defined by antibody Ki-67: a new
      kind of cell cycle-maintaining proteins.
AB  - A decade of studies on the human nuclear antigen defined by monoclonal antibody
      Ki-67 (the "Ki-67 protein") has made it abundantly clear that this structure is
      strictly associated with human cell proliferation and that the expression of this
      protein can be used to assess the growth fraction of a given cell population.
      Until recently the Ki-67 protein was described as a nonhistone protein that is
      highly susceptible to protease treatment. We have isolated and sequenced cDNAs
      encoding for this antigen and found two isoforms of the full length cDNA of 11.5
      and 12.5 kb, respectively, sequence and structure of which are thus far unique.
      The gene encoding the Ki-67 protein is organized in 15 exons and is localized on
      chromosome 10. The center of this gene is formed by an extraordinary 6845 bp exon
      containing 16 successively repeated homologous segments of 366 bp ("Ki-67
      repeats"), each containing a highly conserved new motif of 66 bp ("Ki-67 motif").
      The deduced peptide sequence of this central exon possess 10 ProGluSerThr (PEST)
      motifs which are associated with high turnover proteins such as other cell cycle
      related proteins, oncogenes and transcription factors, etc. Like the latter
      proteins the Ki-67 antigen plays a pivotal role in maintaining cell proliferation
      because Ki-67 protein antisense oligonucleotides significantly inhibit 3H
      thymidine incorporation in permanent human tumor cell lines in a dose-dependent
      manner.

PMID- 8744727
TI  - Analysis of T cell receptor alpha beta variability in tumor-infiltrating
      lymphocytes in primary and metastatic melanoma.
AB  - The T cell receptor (TCR) alpha beta variable (V) gene family usage of tumor
      infiltrating lymphocytes (TIL) in different primary human malignant melanomas and
      corresponding metastatic lesions were characterized using a recently developed
      method using the reverse transcription coupled polymerase chain reaction (RT
      PCR). This semiquantitative RT-PCR method could be adapted to analysis of
      formalin-fixed, paraffin-embedded histopathological samples of primary tumor
      material and demonstrated to be reproducible and to be useful for the assessment
      of V alpha- and V beta-gene family usage in tumor samples. The TIL in primary
      tumors were observed to preferentially express certain TCR V alpha- and V beta
      gene families: V alpha 4, and V beta 8 were highly expressed in several of the
      primary tumors analyzed using this method. With respect to V alpha 22 and V beta
      8, the preferential expression of these V-gene families was demonstrated to be
      due in situ clonal expansion of T cells by means of cloning and sequencing of the
      CDR3 regions (V-J or V-D-J, respectively) corresponding to the RT-PCR products
      from one of the primary tumors. The observed preferential usage of certain TCR V
      alpha and V beta-genes strongly suggest the in situ clonal expansion of specific
      populations of T cells in accordance with recent results from others. These
      clonal T cell populations probably react with certain melanoma-associated
      peptides presented by specific HLA molecules. The preferential usage of certain V
      alpha- and V beta-gene families observed in several tumors further supports the
      involvement of a limited number of shared melanocyte or melanoma-associated
      peptides. Since the HLA status of the patients is obviously important to
      interpret these results, some of the patients were typed for HLA-A1 and -A2, the
      two most well-characterized restriction elements for melanoma-associated
      antigens, either serologically or by a newly developed RT-PCR method which
      similarly could by applied directly to the tumor material. In TIL in primary
      melanomas, a possible correlation was suggested between HLA-A2 and the
      preferential usage of the TCR V-gene families V alpha 4, V alpha 5, V alpha 22
      and V beta 8, whereas the V beta 3-gene family appeared to be expressed together
      with HLA-A1. The V-gene families which were highly expressed in the primary
      tumors were generally not, or only very weakly, expressed in the corresponding
      metastases and vice versa, possibly reflecting a substantial change in the
      phenotype of the metastatic melanoma target cells. Continued studies of larger
      patient materials will be necessary to extend and validate these conclusions and
      of obvious interest for the further analysis of the T cell response in melanoma.

PMID- 8744728
TI  - HLA-B27 subtypes among the Chukotka Native groups.
AB  - The purpose of this study was to assess the relative frequency of the known HLA
      B27 subtypes in HLA-B27 positive Chukotka natives, which have higher frequencies
      of HLA-B27 (to 40%) and spondyloarthropathies (to 2%) than the Russian Caucasian
      population. Using oligotyping of the polymerase-chain reaction amplified second
      and third exons of the HLA-B27 gene in 86 DNA samples from HLA-B27 positive
      individuals were successfully typed. All had HLA-B*2705, including 4 patients
      with Reiter's syndrome and 5 with ankylosing spondyloarthritis, except one Eskimo
      who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. With
      respect to HLA-B27 subtypes the indigenous populations from the eastern part of
      the Chukotka Peninsula are genetically more closely related to Caucasians than to
      Orientalis.

PMID- 8744729
TI  - Role of hydrophobic amino acids at position 74 of DRB1 chain in rheumatoid
      arthritis.
AB  - We have analyzed HLA class II alleles in a group of 153 Czech children with
      rheumatoid arthritis by PCR and hybridization with oligonucleotide probes. When
      we try to find a common sequence for all DRB1 alleles involved in juvenile and
      adult arthritis, we can notice hydrophobic amino acid at position 74, which is
      present in all these alleles, but not in nonsusceptible alleles, where is the
      hydrophilic amino acid at position 74. In our model, we speculate that the
      hydrophilic amino acid at position 74 creates a such kind of epitope which is not
      suitable for rheumatoid-associated peptides or T cells, and only hydrophobic
      amino acid can permit binding of these peptides or recognition by certain T
      cells. Analyses of the DPB1 sequences have shown that alleles which have a
      negatively charged amino acid at position 69, are more frequent in pauciarticular
      patients while those with a positively charged amino acid are more frequent in
      polyarticular patients. A positively charged amino acid at position 69 might
      present the same rheumatoid associated peptide as susceptible DRB1 alleles. The
      presence of more rheumatoid-associated peptide on the cell surface may cause
      conversion to more severe polyarticular forms. A negatively charged amino acid at
      position 69 could not present this peptide and a low concentration of the peptide
      on the cell surface presented just by DRB1 molecules keeps disease in a
      relatively benign condition of pauciarticular forms.

PMID- 8744730
TI  - Use of specific anti-HLA antibodies in clinical nephrology.
AB  - In order to optimize the regimen of pathogenetic therapy of glomerulonephritis
      with nephrotic syndrome we used transfusions of plasma containing specific anti
      HLA antibodies against the patient's phenotype as a part of the treatment in the
      acute stages of disease. The method was theoretically based on the conception of
      autoimmune genesis of glomerular lesion as well as on the assumption that the
      highest expression of HLA-antigens are on the surface of activated
      immunocompetent cells. In previous experiments in vitro we demonstrated
      immunosuppressive activity of cytotoxic serum on lymphocytes in the absence of
      complement. Stable remission that was associated with the recovery of serum
      IgG/IgM balance and normalization of cellular immunity indices was achieved in
      72% of 50 treated patients after 2-4 transfusions. Immunotherapeutic properties
      of anti-HLA antibodies were also confirmed with preliminary results of plasma
      transfusions in 5 kidney graft recipients. Posttransfusion reactions of a non
      haemolytic type were slight and transient. The data presented allow us to
      conclude that our method may be useful in clinical cases associated with
      undesirable immune activation induced by both auto- and alloantigens.

PMID- 8744731
TI  - Cytokine regulation of monocyte recruitment.
AB  - Phagocytes infiltrating neoplastic tissues have peculiar membrane phenotype and
      functional properties. Tumor-associated macrophages (TAM) play a complex,
      ambiguous role in the regulation of primary tumor growth and metastasis (a
      "macrophage balance"). Yet these cells are strategically located at the very
      interface between tumor and host and represent a potential target for
      immunomodulation. A better understanding of the regulation and function of TAM
      may provide a less empirical basis of or rational design of therapeutic
      approaches, as vividly illustrated by the antitumor activity of i.p. in IFN
      ovarian cancer patients with minimal residual disease resistant to chemotherapy.

PMID- 8744732
TI  - Cytokines in mycobacterial infections: in vitro and ex vivo studies.
AB  - Different species of mycobacteria differ in their capacity to induce the
      production of tumor necrosis factor-alpha (TNF-alpha) by human monocytes in
      vitro. Whereas M. tuberculosis is a potent inducer of TNF-alpha, M. leprae is
      much less potent. TNF-alpha production is found to be associated with the
      availability of H2O2 generated by activated monocytes, as superoxide enhancing
      H2O2 concentration increases and catalase degrading H2O2 decreases TNF-alpha
      production. Furthermore, M. kansasii with high intrinsic catalase induce less TNF
      alpha than mycobacteria with low intrinsic catalase. In vitro infection of
      monocytes with M. tuberculosis leads to an impairment of the antigen-presenting
      capacity, as determined by a reduction of antigen-induced T cell proliferation
      and interferon gamma (IFN-gamma) production. Of crucial importance is this
      impairment is the M. tuberculosis-induced down-modulation of MHC class II
      antigens. The role of TNF-alpha in vivo is reflected in patients with various
      forms of leprosy. In skin lesions of lepromatous leprosy patients TNF-alpha,
      interleukin 1 beta (IL-1 beta), and INF-gamma production are found to be rare,
      whereas these cytokines are well expressed in skin lesions of patients with
      tuberculoid leprosy. After multidrug chemotherapy an increase of local cytokine
      production is found. Taken together, these findings suggest that components of
      mycobacteria may interfere with local cell-mediated immune reactions in vivo. The
      molecular mechanisms involved in these local responses need to be defined.

PMID- 8744733
TI  - Detection of antibodies against foot-and-mouth disease virus using a liquid-phase
      blocking sandwich ELISA (LPBE) with a bioengineered 3D protein.
AB  - A liquid-phase blocking sandwich enzyme-linked immunosorbent assay (ELISA-3D) was
      developed to detect specific antibodies to the 3D protein in sera from foot-and
      mouth disease (FMD) virus (FMDV)-infected animals. The assay uses a nonstructural
      3D recombinant protein and two polyclonal antisera, one for capture (bovine) and
      the other for detector (guinea pig). The specificity of the assay was
      demonstrated by negative results with 101 sera of cattle from the FMD-free zone
      in Argentina and with bovine and porcine sera raised against various RNA and DNA
      viruses. The ELISA-3D was able to detect antibodies in cattle after natural or
      experimental infection with FMDV of A, O, or C types as early as 5 days
      postinfection and at later stages in persistently infected animals. Comparison of
      the results with those obtained with the routinely used agar gel immunodiffusion
      test and a previously described ELISA, both employing a partially purified virus
      infection-associated antigen, shows that the ELISA-3D is highly sensitive and
      specific and gives reproducible results. Its use as a tool for monitoring viral
      activity and for certification of FMDV-free animals is recommended.

PMID- 8744734
TI  - Detection of eastern equine encephalomyelitis virus RNA in formalin-fixed,
      paraffin-embedded tissues using DNA in situ hybridization.
AB  - Eastern equine encephalomyelitis (F.EE) virus was detected in infected formalin
      fixed horse and emu tissues and in infected chicken embryo fibroblasts. Results
      of in situ hybridization using a digoxigenin-labeled 40-base DNA probe
      complementary to a conserved region of the EEE virus RNA compared favorably with
      results of both virus isolation and serum neutralization tests. This technique
      may be useful for diagnosis of EEE virus infection in various animal species,
      especially when fresh tissues are not available for analysis, and also will
      provide a means for studying the involvement of alphaviruses in pathogenesis
      studies.

PMID- 8744735
TI  - Immunohistochemical diagnosis of eastern equine encephalomyelitis.
AB  - An immunohistochemical (IHC) assay was developed for the detection of eastern
      equine encephalomyelitis (EEE) virus antigen in formalin-fixed, paraffin-embedded
      tissues. All cases of EEE diagnosed at the Michigan State University Animal
      Health Diagnostic Laboratory from 1991 through 1994 were evaluated. The diagnosis
      was based on histopathologic examination of the brain and confirmatory virus,
      isolation. Sections of cerebrum from 26 equids and 5 birds were assessed by IHC.
      Histologically normal brain tissues from 2 horses and 1 pheasant and brain
      tissues from 2 cases of equine neurologic disease with diagnoses other than EEE
      served as negative controls. The IHC assay was based on standard streptavidin
      biotin technology, using a commercially available kit and a monospecific
      polyclonal primary antibody preparation derived from murine ascitic fluid.
      Nineteen of 20 equids and all 5 birds positive by histopathology and virus
      isolation were positive for EEE virus antigen by IHC. Three equids with
      histologic lesions compatible with a diagnosis of EEE but negative by virus
      isolation also were negative for virus antigen by IHC. In 3 other equids,
      histopathology and IHC were positive for EEE, but virus isolation was not
      attempted because of contamination of the brain specimen. The IHC assay of
      formalin-fixed, paraffin-embedded brain tissues for EEE virus antigen is a rapid,
      effective test for confirming a histopathologic diagnosis of EEE, and assay
      results correlate well with virus isolation results.

PMID- 8744736
TI  - Immunohistochemistry of transmissible gastroenteritis virus antigens in fixed
      paraffin-embedded tissues.
AB  - An immunohistochemistry technique was developed using fixed tissues to study the
      presence and location of transmissible gastroenteritis virus (TGEV) antigens in
      situ. Experimentally infected gnotobiotic and conventional pigs as well as pigs
      with natural TGEV infection were examined. The staining technique was based on
      detection of the major structural protein of TGEV, the nucleocapsid, by using a
      pool of 3 monoclonal antibodies. Formalin and periodate-lysine-paraformaldehyde
      (PLP)-fixed intestinal tissues from a gnotobiotic pig inoculated with virulent
      TGEV were used to determine optimal antibody concentrations and incubation times.
      The intestinal tissues remained in their respective fixatives for 6 months, and
      serial sections were removed at sequential times and embedded in paraffin blocks.
      PLP and 10% neutral buffered formalin were acceptable fixatives and preserved
      TGEV nucleocapsid antigenicity for up to 6 months. Formalin, in comparison with
      PLP as a fixative, was better for preserving original tissue morphology and
      provided better antigen detection. Conventional crossbred pigs were inoculated
      with virulent TGEV, and animals were euthanized on various postexposure days.
      Intestinal tissues were positive for TGEV nucleocapsid antigens on postexposure
      days 2, 4, and 8. The immunohistochemistry technique detected TGEV antigen in
      stored paraffin-embedded tissues from 14 naturally infected pigs previously
      confirmed as positive for TGEV using a direct immunofluorescence assay on
      intestinal mucosal smears, whereas 9 naturally infected pigs confirmed negative
      for TGEV antigen by the same immunofluorescence assay showed no staining
      consistent with the presence of TGEV antigen. Immunohistochemistry provides a
      method to detect TGEV and possibly other closely related coronaviruses such as
      porcine respiratory coronavirus in situ. A diagnostic test using the same fixed
      tissues processed for histopathology provides veterinary practitioners an
      alternative to delivering live pigs or refrigerated fresh intestinal samples
      containing infectious virus to a diagnostic laboratory. Investigators can utilize
      this technique to retrospectively screen fixed tissues for TGEV antigen.

PMID- 8744737
TI  - Evaluation of a semiautomated latex agglutination test for the detection of
      pseudorabies antibody in swine sera.
AB  - Rapid screening of large numbers of swine sera for antibody is an essential
      element in the current eradication program for pseudorabies in the United States.
      We evaluated a recently introduced commercial semiautomated latex agglutination
      test (LAT) kit for pseudorabies antibody. A total of 1,191 swine sera were tested
      using the new procedure and 3 established tests: the manual LAT, the serum
      neutralization test (SNT), and an enzyme-linked immunosorbent assay (ELISA).
      There was close agreement among results of semiautomated LAT, the manual LAT, and
      ELISA but less agreement between semiautomated LAT and SNT. Overall, the
      sensitivities of the 4 tests were as follows: semiautomated LAT = manual LAT >
      ELISA > SNT. For 74 samples of known pseudorabies antibody status, the overall
      specificities were as follows: semi-automated LAT = manual LAT = SNT > ELISA.
      Because of its relative insensitivity, the SNT should no longer be considered the
      official "gold" standard for pseudorabies testing in the on-going eradication
      program. However, because no single test was perfect for all samples, a scheme
      including 3 tests in the following sequence is recommended: 1) screening using
      semiautomated LAT or ELISA and 2) confirmation testing of positives by manual LAT
      and SNT, with any sample that tests positive by any 2 tests being regarded as
      true positive.

PMID- 8744738
TI  - Epitheliocystis infection in cultured white sturgeon (Acipenser transmontanus):
      antigenic and ultrastructural similarities of the causative agent to the
      chlamydiae.
AB  - A mild to moderate branchial epitheliocystis infection was diagnosed in
      subyearling (11 months old, 250-300 g) white sturgeon (Acipenser transmontanus)
      from a private culture facility with a 4-8% mortality in the population. Infected
      branchial epithelial cells contained the coccoid to coccobacillary
      epitheliocystis organisms, which appeared as cytoplasmic inclusions composed of a
      fine, homogeneous, dense, basophilic, granular material. The infected cells were
      variably enlarged with spherical to oval profiles and were randomly distributed
      throughout the branchial epithelium. The cytoplasmic inclusions stained positive
      with Macchiavello stain but negative with Brown and Brenn, periodic acid-Schiff,
      and Gimenez stains. Expression of chlamydial antigen was demonstrated within the
      cytoplasmic inclusions using a standard peroxidase-antiperoxidase
      immunohistochemical technique. Three stages of coordinated intracellular
      development were recognized by electron microscopy. The reticulate bodies were
      oval to spherical and 0.4-0.8 x 0.5-1.4 microns but often exhibited a pleomorphic
      and convoluted appearance because of variable membrane invaginations and
      evaginations suggestive of uneven fission and budding. Separate host cells
      contained intermediate bodies that were spherical to oval and 0.2-0.4 x 0.3-0.6
      microns although often observed in the process of apparent uneven division. The
      presence of a cap or plaque composed of hexagonally arrayed fibrillar surface
      projections was initially recognized in this stage. A homogeneous population of
      0.3-0.4 microns oval elementary bodies were observed separately in individual
      host cells. This developmental stage had a single, dense, compact, eccentrically
      located cytoplasmic condensation that occurred opposite to the location of the
      cap of hexagonally arrayed fibrillar surface projections. Morphologic
      characteristics of the epitheliocystis organism in these white sturgeon were
      similar to those previously described in other teleosts and expands the species
      catalogue of epitheliocystis infection. Furthermore, the ultrastructural
      similarities to the chalmydiae and the immunohistochemical detection of
      chlamydial antigen provides further evidence that the epitheliocystis agent is
      related to members of the Chlamydiales. Although the infection was considered
      mild to moderate and could not be definitively attributed to the mortality in
      this population, the potential adverse impact of epitheliocystis infection on
      sturgeon culture should be considered especially in intensive fish culture
      operations.

PMID- 8744739
TI  - Application of a polymerase chain reaction assay for detection of proliferative
      enteritis-affected swine herds.
AB  - A polymerase chain reaction (PCR) assay was used to confirm the presence of ileal
      symbiont (IS) intracellularis in 3 swine herds with a history of proliferative
      enteritis (PE). Two pooled fecal specimens, each comprising 5 individual stool
      samples, were collected from pen floors to screen for the presence of IS
      intracellularis and determine the age range of pigs shedding the organism. IS
      intracellularis was detected in the feces of clinically normal 10-25-week-old
      grower/finisher pigs, indicating that this age range of pigs was the main source
      of infection for younger nursery pigs. Shedding continued without clinical
      disease when 10-100 g/ton of tylosin or 10 g/ton of chlortetracycline was added
      to the feed. PCR testing of pooled fecal samples can be used to identify groups
      of pigs affected with PE. The results of this study indicate that this PCR assay
      has the potential to accurately assess the IS intracellularis infection status of
      swine herds and the association of IS intracellularis with PE and growth
      performance.

PMID- 8744740
TI  - Phenotypic and ribosomal RNA characterization of Arcobacter species isolated from
      porcine aborted fetuses.
AB  - Aerotolerant organisms resembling Campylobacter, now designated as Arcobacter,
      have been described from aborted farm animals and from cases of human enteritis
      worldwide. The goals of this study were 1) to attempt to recover Arcobacter spp.
      from cases of porcine abortion, 2) to characterize these isolates by phenotype
      and ribotype, and 3) to compare the usefulness of ribotype and phenotype patterns
      for identifying Arcobacter butzleri and the DNA hybridization groups 1A and 1B of
      A. cryaerophilus. Isolates of Arcobacter spp. from North Carolina and Iowa were
      recovered from porcine tissues. In Iowa, Arcobacter spp. were recovered from 43%
      (13/30) of porcine abortion cases evaluated. Isolations were made from placenta
      (44%), kidney (44%), and stomach contents (12%), which were the only tissues
      examined. The most reliable biochemical tests for A. butzleri included growth in
      1% glycine and in 1.5% NaCl, weak catalase activity, and resistance to cadmium
      chloride. Arcobacter cryaerophilus strains were characterized by strong catalase
      activity and sensitivity to cadmium chloride. The DNA hybridization groups 1A and
      1B of A. cryaerophilus could not be distinguished by biochemical tests. This
      represents the first description of A. cryaerophilus DNA group 1A in animals
      within the United States.

PMID- 8744741
TI  - Novel indirect fluorescent antibody test for Lyme disease.
AB  - An indirect fluorescent antibody (IFA) test was developed using a novel format of
      Borrelia burgdorferi organisms adhered to a monolayer of cultured endothelial
      cells derived from an equine tumor. Sensitivity and specificity of the new IFA
      test for detecting anti-B, burgdorferi antibodies were evaluated using sera from
      dogs inoculated with live B. burgdorferi or vaccinated with B. burgdorferi
      bacterin or leptobacterins and from unvaccinated specific-pathogen-free (SPF)
      dogs. To compare the new IFA test with existing tests, serum samples were
      submitted to independent laboratories to be tested by enzyme-linked immunosorbent
      assay (ELISA) and a traditional IFA test. Samples were also tested with 2
      commercially available membrane-bound ELISA kits. Both Borrelia-inoculated dogs
      and dogs vaccinated with B. burgdorferi bacterin developed levels of antibody
      detectable by the new IFA test. Dogs vaccinated with a combination canine vaccine
      or leptobacterin for food animal use developed detectable levels of antibody
      against Leptospira but remained seronegative for Borrelia by the new IFA test, as
      did the unvaccinated SPF dogs. The new IFA test was sensitive, detecting
      antibodies against B. burgdorferi as early as 7 days postinoculation. It was also
      specific, showing no cross-reactivity with anti-Leptospira antibodies induced by
      vaccination with leptobacterins. The new IFA test compared favorably with both
      the standardized traditional IFA test and ELISA. Results from both membrane-bound
      ELISA kits were not consistent when compared with each other or with the new IFA
      test. The new IFA test had low nonspecific fluorescence, which made it easier to
      evaluate and reduced the human error and variability of test results.

PMID- 8744742
TI  - Streptobacillus moniliformis infection in Swiss white mice.
AB  - An epizootic of disease attributed to infection with Streptobacillus moniliformis
      occurred in a colony of Swiss white mice. The mortality rate among the 180
      breeding females in the 6 affected pens was 100%, and most of the sucking young
      died from starvation. Acute septicemia, subacute septicemia, and polyarthritis
      were the 3 forms of disease observed. Clinically, septicemic mice either were
      found dead or were depressed and hunched for 1-2 days prior to death. About a
      half of these mice had brown skin crusts overlying the mammae. Pathologic
      findings in cases of acute septicemia were few; in mice with subacute septicemia,
      there was acute, multifocal, suppurative, embolic interstitial nephritis, and the
      arthritic form was characterized by many subcutaneous and periarticular
      abscesses. Severe, acute, diffuse neutrophilic dermatitis was responsible for the
      brown skin crusts. The S. moniliformis isolate conformed morphologically and
      physiologically to classical descriptions of the organism. The infection may have
      gained entry to the colony via wild rats.

PMID- 8744743
TI  - Dairy cattle abortion in California: evaluation of diagnostic laboratory data.
AB  - A descriptive study was undertaken on 595 dairy cattle abortion submissions to
      the California Veterinary Diagnostic Laboratory System from July 1, 1987, to
      December 31, 1989, to determine the etiologic nature and distribution (seasonal
      and geographical) of dairy cattle abortion in California as reflected by
      laboratory submissions. Univariate analysis was performed to characterize
      abortion-related submissions by farm and laboratory variables, and logistic
      regression analysis was performed to determine factors that may influence success
      of abortion diagnosis in the laboratory. The proportions of dairies that
      submitted abortion-related specimens from northern, central, and southern
      milksheds during the 2.5-year period were 20.3%, 15.7%, and 13.1%, respectively,
      and 60% of submissions were from medium-sized (200-999 cows) dairies. Submissions
      consisted of fetus (58%), placenta (2%), fetus and placenta (12%), and fetus,
      placenta, and maternal blood (0.84%); fetal tissues and uterine fluid constituted
      the rest. An apparent pattern in abortion submissions was indicated by a peak in
      submissions during the winter and summer of 1988 and 1989. Infectious agents were
      associated with 37.1% of submissions; noninfectious causes, 5.5%, and
      undetermined etiology, 57.3%. Bacterial abortion accounted for 18% of etiologic
      diagnoses; protozoal, 14.6%; viral, 3.2%; and fungal, 1.3%. Submissions
      comprising fetus, placenta, maternal blood, or their combinations were associated
      with a higher likelihood of definitive diagnosis for abortion than tissues, as
      were fresher specimens and submissions associated with the second trimester of
      fetal gestation.

PMID- 8744744
TI  - Bovine hereditary zinc deficiency: lethal trait A 46.
AB  - Bovine hereditary zinc deficiency, also referred to as Adema disease, is an
      autosomal recessive disorder which results in inadequate amounts of zinc being
      absorbed from the gastrointestinal tract and leads to a number of clinical
      abnormalities. Using semen from a homozygous affected bull and obligate
      heterozygote cows in embryo transfer studies, 7 offspring were obtained. These
      included 5 affected calves and 1 heterozygous carrier; the seventh calf died
      within 48 hours of birth undiagnosed. One unaffected, unrelated bull calf was
      raised as a control. All the calves were raised and maintained under similar
      management conditions designed to minimize secondary complications that would
      obscure the clinical and biochemical observations of a zinc deficient state. The
      first clinical manifestation of zinc deficiency was diarrhea, followed by skin
      lesions, poliosis, and a decreased ability to sustain a suckle reflex. Trace
      mineral analysis of plasma blood samples revealed that plasma zinc concentrations
      of all the calves were normal at birth; however, they gradually declined in
      affected calves over the course of 3-8 weeks postpartum to below 0.5 ppm.
      Biochemical analysis of serum samples showed alkaline phosphatase activity
      consistently paralleled changes in the plasma zinc concentrations. The oral
      administration of zinc acetate caused a reversal of all clinical, biochemical,
      and histologic abnormalities in affected calves. The study of these affected
      calves allows further insight into the biological role of zinc as well as
      provides an animal model for the continued investigation of the human homologue
      acrodermatitis enteropathica.

PMID- 8744745
TI  - Blood-lipid and lactation-stage factors affecting serum vitamin E concentrations
      and vitamin E cholesterol ratios in dairy cattle.
AB  - The distribution of cholesterol and vitamin E among the various lipoprotein
      density fractions in bovine blood was measured. The percentage of total plasma
      vitamin E and cholesterol in the various lipoprotein fractions was very-low
      density lipoprotein, 2% and 2%, respectively; low-density lipoprotein, 17% and
      22%, respectively, and high-density lipoprotein. 77% and 72%, respectively. Only
      3% of plasma vitamin E was not associated with the lipoproteins. Vitamin E
      cholesterol ratios were not significantly different among lipoprotein fractions
      (P = 0.3). These results indicate that vitamin E and cholesterol are distributed
      in equal proportions among lipoprotein fractions. Moreover, the results suggest
      that variation in the proportions of lipoproteins in the different density
      fractions would not affect the overall vitamin E cholesterol ratio of plasma. The
      results further imply that the total plasma vitamin E cholesterol ratio is a
      valid relative estimator of the vitamin E concentration per lipoprotein particle,
      regardless of the density distribution of particles. Total serum vitamin E and
      cholesterol concentrations and their ratio were then determined in commercial
      diary cattle in various phases of the lactation cycle. There was a significant
      lactation-stage effect on the serum concentration of each analyte, as well as on
      their ratio. However, the magnitude of the effect was much less for the ratio
      than for either vitamin E or cholesterol alone. These results imply that
      lactation stage affects serum vitamin E concentrations by influencing both the
      concentration of lipoprotein particles and the concentration of vitamin E within
      individual particles.

PMID- 8744746
TI  - Effects of environmental heat and intake of tall fescue seed infested with
      Acremonium coenophialum on the acid-base status of young bulls.
AB  - Effects of high environmental temperature and dietary intake of tall fescue
      (Festuca arundinacea) seed containing the endophyte Acremonium coenophialum on
      bovine acid-base status were studied using 3 groups of bull calves (2 Simmental,
      1 Angus). Experimental animals were housed in controlled-climate chambers and
      subjected to gradual increases in environmental temperature, first while being
      fed an endophyte-free diet and then while being fed a diet containing 17%
      endophyte-infested fescue seed. Marked acid-base disturbances were not observed
      in any animals. In general, Pco2, HCO3-, base excess, and arterial blood pH
      values were reduced in response to heat stress, both with endophyte-free and
      endophyte-containing diets. In most individuals anion gap increased. These
      results reflected metabolic compensation for mild chronic alveolar
      hyperventilation and retention of organic acids. These findings suggest that,
      under conditions similar to those found during the summer in central Missouri,
      normal cattle should not be at great risk of developing respiratory alkalosis or
      other severe acid-base disturbances as a result of heat stress and/or intake of
      tall fescue endophyte.

PMID- 8744747
TI  - Alveolar macrophages as a diagnostic sample for detecting natural infection of
      pigs with porcine reproductive and respiratory syndrome virus.

PMID- 8744748
TI  - Use of nonradioactive cDNA probes to differentiate porcine respiratory
      coronavirus and transmissible gastroenteritis virus isolates.

PMID- 8744749
TI  - Rotaviruses associated with neonatal lamb diarrhea in two Wyoming shed-lambing
      operations.

PMID- 8744750
TI  - Actinobacillus suis-like organisms associated with septicemia in neonatal calves.

PMID- 8744751
TI  - Proliferative enteritis associated with Lawsonia intracellularis (ileal symbiont
      intracellularis) in white-tailed deer.

PMID- 8744752
TI  - Proliferative enteropathy in a foal caused by Lawsonia intracellularis-like
      bacterium.

PMID- 8744753
TI  - Mycobacterium avium complex abortion in a mare.

PMID- 8744754
TI  - Periodic recurrence of gangrenous dermatitis associated with Clostridium septicum
      in a broiler chicken operation.

PMID- 8744755
TI  - Metastatic renal carcinoma in an African grey parrot (Psittacus erithacus
      erithacus).

PMID- 8744756
TI  - Malignant ovarian tumors in two heifers.

PMID- 8744757
TI  - Endogenous lipid pneumonia (multifocal alveolar histiocytosis) in raccoons
      (Procyon lotor).

PMID- 8744758
TI  - Incidental subcutaneous gordiid parasitism in a cat.

PMID- 8744759
TI  - Phylogenetic relationships among the major lineages of the birds-of-paradise
      (Paradisaeidae) using mitochondrial DNA gene sequences.
AB  - Complete mitochondrial cytochrome b gene sequences were determined from 12
      species of the Australo-Papuan birds-of-paradise (Paradisaeidae) representing 9
      genera. Phylogenetic analysis of these and 5 previously published sequences
      reveals a radiation of the main paradisaeinine lineages that took place over a
      relatively short evolutionary time scale. The core paradisaeinines are resolved
      as the monophyletic sister-group to the crow-like manucodines. The genus Parotia
      is basal to other paradisaeinines and is not closely related to the
      morphologically similar genera Ptiloris and Lophorina. Three major clades within
      the paradisaeinine ingroup include: (1) Cicinnurus and Diphyllodes, (2) Ptiloris
      and Lophorina, and (3) the genus Paradisaea. The monotypic genus Seleucidis is
      apparently closely related to clades (1) and (2). Cytochrome b sequences did not
      provide evidence for the monophyly of the sicklebill genera Epimachus and
      Drepanornis. The paradisaeid tree is characterized by short internodal distances.
      Thus, some clades cannot be strongly resolved by cytochrome b sequences alone.

PMID- 8744760
TI  - Phylogenetic use of noncoding regions in the genus Gentiana L.: chloroplast trnL
      (UAA) intron versus nuclear ribosomal internal transcribed spacer sequences.
AB  - Sequence divergence was estimated within noncoding sequences of both chloroplast
      DNA (cpDNA) trnL (UAA) intron and nuclear ribosomal DNA (nrDNA) internal
      transcribed spacer sequences (ITS1 and ITS2) for 10 species of the genus Gentiana
      L. (Gentianaceae). Comparisons of evolutionary rates among these sequences (cpDNA
      versus nrDNA, ITS1 versus ITS2) were performed. It appears that sequence
      divergence is on average two to three times higher in ITSs than in the trnL
      intron sequences and higher in ITS1 than in ITS2. Both the cpDNA intron and ITSs
      of nrDNA give concordant phylogenetic trees. However, the ITS-based phylogeny
      displays higher bootstrap values. At the intrageneric level, at least in
      Gentiana, ITSs (especially ITS2) sequences seem to be more appropriate in the
      assessment of plant phylogenies. Nevertheless, the cpDNA trnL intron seems to be
      preferable at the intergeneric level.

PMID- 8744761
TI  - Phylogenetics of the Caprinae based on cytochrome b sequence.
AB  - Relationships within the subfamily Caprinae have never been fully resolved.
      Phylogenies have been proposed based on morphological, behavioral, ecological,
      and some molecular comparisons. Because of the relatively poor fossil record of
      the Caprinae, paleontological evidence has not been extensively used in
      phylogenetic reconstruction for this group. Traditionally, four tribes: Saigini,
      Ovibovini, Rupicaprini, and Caprini, have been recognized. We investigated
      relationships within the Caprinae by comparing sequences of the cytochrome b gene
      of mitochondrial DNA from 11 species of Caprinae and 1 Bovinae species. Our
      analyses suggest that revisions to previous phylogenies, including the
      dissolution of the Ovibovini, are warranted.

PMID- 8744762
TI  - Phylogeography of brown bears (Ursus arctos) of Alaska and paraphyly within the
      Ursidae.
AB  - Complete nucleotide sequences of the mitochondrial cytochrome b, tRNA(prolime),
      and tRNA(threonine) genes were described for 166 brown bears (Ursus arctos) from
      10 geographic regions of Alaska to describe natural genetic variation, construct
      a molecular phylogeny, and evaluate classical taxonomies. DNA sequences of brown
      bears were compared to homologous sequences of the polar bear (maritimus) and of
      the sun bear (Helarctos malayanus), which was used as an outgroup. Parsimony and
      neighbor-joining methods each produced essentially identical phylogenetic trees
      that suggest two distinct clades of mtDNA for brown bears in Alaska: one composed
      only of bears that now reside on some of the islands of southeastern Alaska and
      the other which includes bears from all other regions of Alaska. The very close
      relationship of the polar bear to brown bears of the islands of southeastern
      Alaska as previously reported by us and the paraphyletic association of polar
      bears to brown bears reported by others have been reaffirmed with this much
      larger data set. A weak correlation is suggested between types of mtDNA and
      habitat preference by brown bears in Alaska. Our mtDNA data support some, but not
      all, of the currently designated subspecies of brown bears whose descriptions
      have been based essentially on morphology.

PMID- 8744763
TI  - Phylogenetics and evolution of the Daphnia longispina group (Crustacea) based on
      12S rDNA sequence and allozyme variation.
AB  - Although members of the crustacean genus Daphnia have been the target of much
      research, there is little understanding of the group's evolutionary history. We
      addressed this gap by inferring a phylogeny for one of the major species groups
      (longispina) using nucleotide sequence variation of a 525-bp segment of the
      mitochondrial 12S rDNA and allozyme variation at 21 loci. We identified the major
      lineages and their relationships, assessed the phylogenetic utility of the few
      morphological characters in the group, and examined Daphnia phylogeography.
      Nuclear and mtDNA phylogenies were generally concordant in recognizing the same
      four species complexes. An exception was the position of Daphnia galeata
      mendotae. The allozyme tree paired this species with the Daphnia rosea lineage,
      whereas the mtDNA trees grouped D. g. mendotae with Daphnia galeata galeata. This
      discordance was consistent with the reticulate evolution of nuclear genes
      supporting the hypothesis that D. g. mendotae represents a case of homoploid
      hybrid speciation. Striking morphological stasis in the longispina group was
      evidenced by its very limited morphological divergence over an estimated 100 MY,
      and by the unusual transitional saturation of the conservative 12S rRNA gene
      within a species group. Phylogenetic inference also provided evidence that
      similarities in cephalic crest shape likely resulted from convergent or parallel
      evolution among species. Endemism at the continental level was indicated for
      previously cosmopolitan species, but the estimated times of these divisions were
      inconsistent with vicariance events suggesting recent dispersal among continents.
      A significant role for divergent selection in new habitats during speciation was
      suggested by the neighboringly sympatric distributions of four sister species
      pairs over broad geographic areas.

PMID- 8744764
TI  - Molecular phylogeny for marine turtles based on sequences of the ND4-leucine tRNA
      and control regions of mitochondrial DNA.
AB  - Marine turtles are divided into two families, the Dermochelyidae and the
      Cheloniidae. The majority of species are currently placed within the two tribes
      of the Cheloniidae, the Chelonini and the Carettini, but debate continues over
      generic and tribal affinities as well as species boundaries. We used nucleotide
      sequences (907 bp) from the ND4-LEU tRNA region and the control region (526 bp)
      of mitochondrial DNA to resolve areas of uncertainty in marine turtle
      (Chelonioidae) systematics. The ND4-LEU tRNA fragment was more conserved than the
      fragment from the control region, with sequence divergences ranging from 0.026 to
      0.148 and 0.067 to 0.267, respectively. Parsimony analysis based only on the ND4
      LEU tRNA data suggests that the hawksbill, Eretmochelys imbricata, lies within
      the tribe Carettni and is closely related to the genus Caretta, but could not
      resolve the position of the flatback, Natator depressus. A similar analysis based
      only on the control region sequence data suggested that N. depressus is
      affiliated with the Chelonini, but failed to resolve the position of E. imbricata
      and the loggerhead, Caretta caretta. In contrast to these results, the
      combination of both data sets with published cytochrome b data produced a
      phylogeny based on 1924 bp of sequence data which resolves the position of E.
      imbricata relative to Caretta and Lepidochelys and joins N. depressus as sister
      to the Carettini. Based on the molecular data, the Chelonini contains the
      Chelonia species, while the Carettini contains the remaining species of
      Cheloniidae. The control region sequence divergence between Pacific and Atlantic
      populations of the leatherback, Dermochelys coriacea, was relatively low (0.0081)
      when compared with the green turtle, Chelonia mydas (0.071-0.074). Atlantic and
      Pacific populations of Ch. mydas were found to be paraphyletic with respect to
      the black turtle, Ch. agassizi, suggesting that the current taxonomic
      designations within the Pacific Chelonia are questionable. This analysis shows
      the utility of combining sequence data for different regions of mtDNA that by
      themselves are insufficient to obtain robust phylogenies.

PMID- 8744765
TI  - A phylogeny for the African treefrog family Hyperoliidae based on mitochondrial
      rDNA.
AB  - Mitochondrial 12S rRNA sequences were used to construct a phylogeny for the
      African treefrog family, Hyperoliidae. The sequences were aligned using the well
      established mt 12S rRNA secondary structure as a map to designate stem and loop
      positions. Conservation of secondary structure permits a more accurate basis for
      assessing homologies than does primary sequence alone. The molecular trees showed
      many similarities to the morphological trees constructed previously. Species
      within a genus always grouped together. The genera Hyperolius, Heterixalus,
      Afrixalus, and Kassina were resolved, but not with statistical significance.
      Leptopelis was the basal group. The analysis shows clearly that Phylyctimantis
      groups with Kassina as it did in Drewes' morphological tree and that Tachycnemis
      groups closely with Heterisxalus, a relationship not suggested by the
      morphological data. Character weighting (including compensatory base changes),
      mitochondrial trees vs gene trees, and the biogeography of the group are
      discussed.

PMID- 8744766
TI  - Phylogenetic relationships among bufonoid frogs (Anura:Neobatrachia) inferred
      from mitochondrial DNA sequences.
AB  - Nucleotide sequences of portions of the mitochondrial 12S and 16S ribosomal RNA
      genes were used to extend a recent study of anuran phylogeny (Hay et al., Mol.
      Biol. Evol. 12: 928-937, 1995) and to further evaluate phylogenetic relationships
      within the Neobatrachia. An analysis of almost 900 nucleotides from each of 8 new
      representatives of the Dendrobatidae, Hylidae, Leptodactyolidae, and
      Myobatrachidae, plus 14 available members of the Neobatrachia provides support
      for 2 major lineages (Bufonoidea and Ranoidea) within this anuran suborder. The
      neotropical Bufonoidea and their derivatives are monophyletic. There is an
      interesting association of the 2 Australian myobatrachids with the South African
      Heleophrynidae, and the Sooglossidae is one of the basal bufonoid lineages.
      Within the New World bufonoid frogs, a monophyletic Dendrobatidae is strongly
      supported. An Australian hylid (Pelodryadinae) shows close affinity with the
      South American hylid Phyllomedusinae. A group composed of Hylinae (Hyla and
      Smilisca), Centrolenidae, Bufonidae, and the hylid Hemiphractinae, with the
      latter two clustered, was supported significantly. The addition of new taxa has
      more clearly defined some relationships within the suborder Neobatrachia and has
      indicated that the families Hylidae, Leptodactylidae, and Myobatrachidae may not
      be monophyletic.

PMID- 8744767
TI  - The presence/absence polymorphism and evolution of the p53 pseudogene in the
      genus Mus.
AB  - Distribution of the p53 pseudogene within the house mouse species (genus Mus) was
      studied with polymerase chain reaction for 37 individuals that were caught at
      different localities. Pseudogene-specific fragments were detected in some, but
      not all, individuals of Mus musculus subspecies regardless of locality and type
      of subspecies. In addition, 3 of 7 individuals belonging to different Mus species
      carried the pseudogene in their genomes. These results show the existence of an
      interspecific presence/absence polymorphism of the p53 pseudogene in mice.
      Sequence analysis of 11 amplified 0.3-kb fragments suggested that the pseudogene
      originated in an ancestral mouse about 7 million years ago. Thus alleles with and
      without the p53 pseudogene have persisted through the mice speciation. The
      evolutionary rate for the p53 functional gene was also estimated to be about 3.3
      x 10(-9) per nucleotide site per year.

PMID- 8744768
TI  - Molecular phylogenetics of honey bee subspecies (Apis mellifera L.) inferred from
      mitochondrial DNA sequence.
AB  - A mitochondrial DNA region encompassing part of the NADH dehydrogenase subunit 2
      and isoleucine transfer RNA genes was PCR amplified, cloned, and sequenced for 14
      morphometrically identified Apis mellifera subspecies and the New World
      "Africanized" honeybee. Twenty different haplotypes were detected and
      phylogenetic analyses supported the existence of 3 or 4 major subspecies groups
      similar to those based on morphometric measurements. However, some discrepancies
      are reported concerning the subspecies composition of each group. Based on the
      sequence divergence of Drosophila (2% per Myr) we found that the four lineages
      may have diverged around 0.67 Myr. The variability found in this region enables
      us to infer phylogenetic relationships and test hypotheses concerning subspecies
      origin, dispersion, and biogeography.

PMID- 8744769
TI  - A phylogeny of the bears (Ursidae) inferred from complete sequences of three
      mitochondrial genes.
AB  - Complete sequences of DNA are described for the cytochrome b tRNA(Thr) and
      tRNA(Pro) genes of mitochondria of four extant species of ursids and compared to
      sequences of four other species of ursids previously studied by us. Phylogenetic
      analyses indicate that the giant panda and the spectacled bear are the basal taxa
      of the ursid radiation. The ursines, a group which includes the sun bear, sloth
      bear, American black bear, Asiatic black bear, brown bear, and polar bear,
      experienced a rapid radiation during the mid Pliocene to early Pleistocene. The
      Asiatic black bear and American black bear are sister taxa. The brown bear and
      polar bear are the most recently derived of the ursines, with the polar bear
      originating from within a clade of brown bears during the Pleistocene. This
      paraphyletic association suggests that the rate of morphological evolution may be
      accelerated relative to that of molecular evolution when a new ecological niche
      is occupied. Calibration of the corrected average number of nucleotide
      differences per site with the fossil record indicates that transitions at third
      positions of codons in the ursid cytochrome b gene occur at a rate of
      approximately 6% per million years, which is considerably slower than comparable
      values reported for other species of mammal.

PMID- 8744770
TI  - An algorithm to analyse the hydrolysis pathway of peptides and proteins by
      sequence analyses of unfractionated digestion mixtures.
AB  - We have designed and implemented on a personal computer a program for identifying
      and quantifying the fragments present in a peptide mixture obtained by
      hydrolysing a polypeptide of known sequence using digesting agents. The
      qualitative data utilized by the main algorithm consist of the target sequence of
      the intact molecule and the amino acid residues identified at each step of the
      automatic sequence analysis of the unfractionated digestion mixture. In this way,
      the sequence of each fragment present in the mixture is quickly reconstructed.
      Furthermore, if the quantitative data of the amino acid residues identified at
      each step of the sequence analysis are utilized, the program will correlate the
      sequence of each fragment to its amount. We furnish an example of the application
      intended for the rapid identification and characterization of the extracellular
      proteinases produced by a basidiomycete fungus, utilizing the bovine insulin beta
      chain as target substrate. A variety of uses for the method are discussed.

PMID- 8744771
TI  - XFINGER: a tool for searching and visualising protein fingerprints and patterns.
AB  - A tool for searching pattern and fingerprint databases is described. Fingerprints
      are groups of motifs excised from conserved regions of sequence alignments and
      used for iterative database scanning. The constituent motifs are thus encoded as
      small alignments in which sequence information is maximised with each database
      pass; they therefore differ from regular-expression patterns, in which alignments
      are reduced to single consensus sequences. Different database formats have
      evolved to store these disparate types of information, namely the PROSITE
      dictionary of patterns and the PRINTS fingerprint database, but programs have not
      been available with the flexibility to search them both. We have developed a
      facility to do this: the system allows query sequences to be scanned against
      either PROSITE, the full PRINTS database, or against individual fingerprints. The
      results of fingerprint searches are displayed simultaneously in both text and
      graphical windows to render them more tangible to the user. Where structural
      coordinates are available, identified motifs may be visualised in a 3D context.
      The program runs on Silicon Graphics machines using GL graphics libraries and on
      machines with X servers supporting the PEX extension: its use is illustrated here
      by depicting the location of low-density lipoprotein-binding (LDL) motifs and
      leucine-rich repeats in a mosaic G-protein-coupled receptor (GPCR).

PMID- 8744772
TI  - Hidden Markov models for sequence analysis: extension and analysis of the basic
      method.
AB  - Hidden Markov models (HMMs) are a highly effective means of modeling a family of
      unaligned sequences or a common motif within a set of unaligned sequences. The
      trained HMM can then be used for discrimination or multiple alignment. The basic
      mathematical description of an HMM and its expectation-maximization training
      procedure is relatively straightforward. In this paper, we review the
      mathematical extensions and heuristics that move the method from the theoretical
      to the practical. We then experimentally analyze the effectiveness of model
      regularization, dynamic model modification and optimization strategies. Finally
      it is demonstrated on the SH2 domain how a domain can be found from unaligned
      sequences using a special model type. The experimental work was completed with
      the aid of the Sequence Alignment and Modeling software suite.

PMID- 8744773
TI  - Motif identification neural design for rapid and sensitive protein family search.
AB  - A new method, the motif identification neural design (MOTIFIND), has been
      developed for rapid and sensitive protein family identification. The method is an
      extension of our previous gene classification artificial neural system and
      employs new designs to enhance the detection of distant relationships. The new
      designs include an n-gram term weighting algorithm for extracting local motif
      patterns, an enhanced n-gram method for extracting residues of long-range
      correlation, and integrated neural networks for combining global and motif
      sequence information. The system has been tested and compared with several
      existing methods using three protein families, the cytochrome c, cytochrome b and
      flavodoxin. Overall it achieves 100% sensitivity and > 99.6% specificity, an
      accuracy comparable to BLAST, but at a speed of approximately 20 times faster.
      The system is much more robust than the PROSITE search which is based on simple
      signature patterns. MOTIFIND also compares favorably with BLIMPS, the Hidden
      Markov Model and PROFILESEARCH in detecting fragmentary sequences lacking
      complete motif regions and in detecting distant relationships, especially for
      members of under-represented subgroups within a family. MOTIFIND may be generally
      applicable to other proteins and has the potential to become a full-scale
      database search and sequence analysis tool.

PMID- 8744774
TI  - Object-oriented sequence analysis: SCL--a C++ class library.
AB  - SCL (Sequence Class Library) is a class library written in the C++ programming
      language. Designed using object-oriented programming principles, SCL consists of
      classes of objects performing tasks typically needed for analyzing DNA or protein
      sequences. Among them are very flexible sequence classes, classes accessing
      databases in various formats, classes managing collections of sequences, as well
      as classes performing higher-level tasks like calculating a pairwise sequence
      alignment. SCL also includes classes that provide general programming support,
      like a dynamically growing array, sets, matrices, strings, classes performing
      file input/output, and utilities for error handling. By providing these
      components, SCL fosters an explorative programming style: experimenting with
      algorithms and alternative implementations is encouraged rather than punished. A
      description of SCL's overall structure as well as an overview of its classes is
      given. Important aspects of the work with SCL are discussed in the context of a
      sample program.

PMID- 8744775
TI  - FastAlert--an automatic search system to alert about new entries in biological
      sequence databanks.
AB  - This paper describes a new tool enabling awareness of new sequence databank
      entries of interest. The FastAlert system relieves the researcher from the burden
      of repeating FASTA searches in order to keep up with the rapidly growing amount
      of information found in biological sequence databanks. The query sequence can be
      submitted from any computer connected to the Internet. Upon registration, the
      databank, including the updates, is scanned at periodic intervals with the
      sequence provided. The results, so-called FastAlert reports, are delivered via
      electronic mail. The reports contain the FASTA best-scores list and the
      similarity statistics for each entry listed.

PMID- 8744776
TI  - Using substitution probabilities to improve position-specific scoring matrices.
AB  - Each column of amino acids in a multiple alignment of protein sequences can be
      represented as a vector of 20 amino acid counts. For alignment and searching
      applications, the count vector is an imperfect representation of a position,
      because the observed sequences are an incomplete sample of the full set of
      related sequences. One general solution to this problem is to model unobserved
      sequences by adding artificial 'pseudo-counts' to the observed counts. We
      introduce a simple method for computing pseudo-counts that combines the diversity
      observed in each alignment position with amino acid substitution probabilities.
      In extensive empirical tests, this position-based method out-performed other
      pseudo-count methods and was a substantial improvement over the traditional
      average score method used for constructing profiles.

PMID- 8744777
TI  - An extensible network query unification system for biological databases.
AB  - Database federation enables biological researchers to utilize resources more
      effectively, creating an environment in which the researcher can query multiple
      data sources without spending time learning new query mechanisms or issuing
      redundant queries which need to be integrated. Several mechanisms exist to
      federate databases. The ENQUire system is a network database federation system
      which uses a World-Wide-Web (WWW) interface to connect the users to various
      databases. Generic queries entered via a query generator form are sent in
      parallel to multiple databases, and the results are presented to the user in a
      unified format. All forms building, query generation, and results translation is
      done on the fly, and individual database translation modules can be added
      dynamically. ENQUire is a flexible answer to the problems of database federation
      on the WWW.

PMID- 8744778
TI  - A Tcl-based SRS v. 4 interface.
AB  - A new SRS (Sequence Retrieval System) user interface has been developed for SRS
      v.4. Key features are the support of simple character-oriented (ASCII, VT100)
      terminals by coding in Tcl augmented by some dedicated Curses calls, support of
      graphics terminals in an X-Windows version by using the Tk extension to Tcl, and
      support of a client/server environment by using the TDP extension to Tcl. The
      Sequence Retrieval System (SRS) is a powerful tool for the fast extraction of
      information from flat file libraries (Etzold and Argos, 1993) and has rapidly
      established itself as a major research instrument for the bio-informatics
      community. Internally the system employs a query language, which is user
      accessible through either a command-line user interface, 'getz', or a more user
      friendly, character-oriented window interface. For SRS versions up to release v.
      3, this window interface supported VT100-compatible terminals. Because of major
      changes in the underlying SRS libraries, the v. 3 interface became fully
      incompatible with the most recent version of SRS (v. 4.x). Thus the many users
      with only a simple terminal/terminal emulator connection were either deprived of
      access to SRS, or were forced to use the ASCII WWW client LYNX. This prompted us
      to develop a character-oriented SRS v. 4 window interface with the look and feel
      of its SRS v. 3.1 predecessor and coded to be as library independent as possible
      to maintain compatibility with future SRS releases. In addition, some
      'extensions' were coded to widen the applicability to graphics terminals and to a
      client/server environment. At the time of preparation of this paper, the SRS
      interface described had been implemented in one form or another on most EM Bnet
      nodes and on all the platforms given in Table II. The code has been stored at the
      EMBL in Heidelberg, where it will be available, with installation instructions
      and scripts, as part of the SRS distribution.

PMID- 8744779
TI  - SIGNAL SCAN 4.0: additional databases and sequence formats.
AB  - SIGNAL SCAN is a program that utilizes transcription factor databases to find
      potential transcription factor binding sites in DNA sequences. The program is now
      in its fourth version. SIGNAL SCAN 4 now includes, in addition to the
      Transcription Factor Database, the TRANSFAC and IMD (Information Matrix Database)
      databases. In addition, it now accepts GCG and FASTA formatted DNA sequences in
      addition to Staden formatted sequences. SIGNAL SCAN is available for both IBM
      compatible PC and Unix workstation platforms.

PMID- 8744780
TI  - International Sport Nutrition Conference. Bloomington, Minnesota, September 1995.
      Proceedings.

PMID- 8744781
TI  - Physical activity, fat balance, and energy balance.
AB  - In this paper, we review the impact of physical activity on energy and
      macronutrient balances. Stability of body weight and body composition depends on
      reaching a steady-state where the amount and composition of energy ingested are
      equal to the amount and composition of energy expended. We describe how a
      person's level of physical activity can have a significant impact on determining
      the level of body weight and body fatness at which that steady-state is reached.
      First, physical activity can directly affect both total energy intake and total
      energy expenditure. Physical activity can also affect fat balance, and it is
      becoming clear that imbalances in total energy are largely imbalances in fat.
      High levels of physical activity should help individuals reach fat and energy
      balances at lower levels of body fatness than would have been achieved at lower
      levels of physical activity.

PMID- 8744782
TI  - Water and electrolyte replenishment in the exercising child.
AB  - This article reviews studies, mostly from the authors' laboratory, on children's
      sweating rates and composition, voluntary drinking patterns during prolonged
      exercise in the heat, taste perception of beverages, and the importance of fluid
      flavor and composition in preventing voluntary dehydration. Subjects were
      children, exposed for 90 to 180 min to intermittent bouts of cycling (45-50%
      maximal O2 uptake) in a climatic chamber (mostly at 35 degrees C, 40-50% relative
      humidity). There were five main findings: When given unflavored water ad libitum,
      children dehydrated progressively and their core temperature increased faster
      than in adults. When offered drinks with various flavors, children preferred
      grape to other flavors. When given grape-flavored water during intermittent
      exercise in the heat, children voluntarily drank 44.5% more than with unflavored
      water. When given grape-flavored carbohydrate-electrolyte solution, they
      voluntarily drank 91% more than with unflavored water. Finally, such consumption
      of carbohydrate-electrolyte solution was sufficient to prevent voluntary
      dehydration during 180-min intermittent exercise in the heat.

PMID- 8744783
TI  - Eating disorders, energy intake, training volume, and menstrual function in high
      level modern rhythmic gymnasts.
AB  - This study examined clinical and subclinical eating disorders (EDs) in young
      Norwegian modern rhythmic gymnasts. Subjects were 12 members of the national
      team, age 13-20 years, and individually matched nonathletic controls. All
      subjects participated in a structured clinical interview for EDs, medical
      examination, and dietary analysis. Two of the gymnasts met the DSM-III-R criteria
      for anorexia nervosa, and 2 met the criteria for anorexia athletica (a
      subclinical ED). All the gymnasts were dieting in spite of the fact that they
      were all extremely lean. The avoidance of maturity, menstrual irregularities,
      energy deficit, high training volume, and high frequency of injuries were common
      features among the gymnasts. Ther is a need to learn more about risk factors and
      the etiology of EDs in different sports. Coaches, parents, and athletes need more
      information about principles of proper nutrition and methods to achieve ideal
      body composition for optional health and athletic performance.

PMID- 8744784
TI  - Working with young athletes: views of a nutritionist on the sports medicine team.
AB  - Athletes are influenced by coaches, other athletes, media, parents, the national
      sport governing body, members of the sports medicine team, and the athlete's own
      desire for success. It is impossible, therefore, for one member of the sports
      medicine team to unilaterally determine workable solutions that enhance
      performance and diminish health problems in an athlete. A focus on ensuring that
      the athlete can perform to the best of her ability is a key to encouraging
      discussion between the nutritionist, athlete, and coach. Using the assumption
      that health and top athletic performance are compatible, this focus on
      performance provides a discussion point that all parties can agree to and, if
      approached properly, also fulfills the nutritionist's goal of achieving optimal
      nutritional status. Membership on the sports medicine team mandates that the
      nutritionist know the paradigms and health risks associated with the sport and
      develop assessment and feedback procedures specific to the athlete's needs.

PMID- 8744785
TI  - The role of medium-chain triglycerides in exercise.
AB  - Studies investigating fat as a fuel for exercise have found that increasing free
      fatty acids during exercise tends to spare muscle glycogen due to increased
      utilization of free fatty acids for energy, which in turn can enhance the
      capacity for endurance exercise. Medium-chain triglycerides do not delay gastric
      emptying or absorption. They are broken down by lipase in the stomach and
      duodenum to glycerol and medium-chain fatty acids (MCFA). Since MCFAs are
      metabolized as quickly as glucose, it has been speculated that they might provide
      an alternative carbon source for the muscle during prolonged exercise. While the
      majority of studies investigating the role of medium-chain triglycerides and
      exercise have found no sparing effect of muscle glycogen after consumption of
      medium-chain triglycerides, two recent studies have presented conflicting
      results. This review will investigate the speculated role of medium-chain
      triglycerides as an alternative fuel source for exercising muscles and will
      discuss the possibility that medium-chain triglycerides preserve muscle glycogen
      during exercise.

PMID- 8744786
TI  - Nutritional aspects of amenorrhea in the female athlete triad.
AB  - Female athletes experience a high incidence of menstrual abnormalities. This has
      critical health consequences because amenorrheic athletes are at greater risk of
      developing osteopenia and bone injury compared to normally menstruating athletes
      or nonathletic normally cycling females. Female performers and athletes are also
      at risk for developing disordered eating behaviors. There appears to be a
      connection between menstrual dysfunction, athletic training, and disordered
      eating, but how they relate is not fully understood. In this paper we explore how
      low calorie intakes, nutritional inadequacies, vegetarianism, low body fat
      stores, and specific training behaviors may contribute to the abnormal menstrual
      patterns seen in this population. Recommendations for the detection and
      prevention of eating and training problems and consequent menstrual abnormalities
      are included.

PMID- 8744787
TI  - Assessment of body composition in youths and relationship to sport.
AB  - Body composition assessment techniques provide estimates of percent body fat
      (%BF), fat mass (FM), and fat-free mass (FFM) based on indirect assessment models
      and methods. Prediction equations for %BF developed using a two-component model
      based on adult body composition constants with overestimate %BF in youths,
      especially prepubescent youths. Body composition prediction equations that have
      been validated and cross-validated using multiple-component criterion models
      which include measurements of body density and the water and mineral components
      of FFM provide the most accurate means for assessment of body composition in
      youths. Use of appropriate prediction equations and proper measurement
      techniques, for either bioelectrical impedance or skinfolds, results in body
      composition estimates with standard errors of estimate (prediction errors) of 3
      to 4% BF and 2.0 to 2.5 kg of FFM. Poor measurement technique and inappropriate
      prediction equations will result in much larger prediction errors.

PMID- 8744788
TI  - Role of energy balance in athletic menstrual dysfunction.
AB  - The cessation of menstrual function in the female athlete may reflect her
      inability to adapt to the environmental and lifestyle stressors associated with
      training and competition. As society's emphasis on thinness, dieting, and
      exercise continues to increase, so will the incidence of menstrual dysfunction in
      active females. Unfortunately, some individuals view athletic menstrual
      dysfunction as a benign consequence of strenuous exercise. Conversely, it is most
      likely a strong indicator of overtraining and a marker for future decrements in
      performance, and it can have long-term health consequences. Thus, it is
      imperative that the active female be appropriately educated regarding the adverse
      consequences of menstrual dysfunction and the interventions available. This paper
      focuses on the most current information regarding athletic menstrual dysfunction
      and its multifactorial etiology, especially the role of energy drain. In
      addition, common misconceptions, adverse health and performance effects, and
      available treatment options are discussed.

PMID- 8744789
TI  - Ergogenic aids: evaluating sport nutrition products.
AB  - The desire to win leads physically active individuals to look for anything to
      improve performance. Many ergogenic aids are available; however, claims made
      about many of these products are not appropriate. To evaluate such products, one
      must consider the physiological sense of the claims, the supportive evidence
      provided, the research articles quoted, and the legal and health implications of
      use.

PMID- 8744790
TI  - Introduction: human pathology within the broad scope of comparative pathology.
AB  - Pathologic integration is the basic phenomenon of comparative pathology. Since
      man evolved as earth's most influential species, he was unequally influenced the
      progression and prevention of diseases in himself and other species. This has
      both positive and negative ramifications. Positive influences have been life
      style, the prolongation of life under healthy conditions and medical progress as
      seen in the treatment of diabetes mellitus, dental hygiene and other factors,
      such as the decrease of infectious and parasitic diseases, which are still
      dominating factors in developing nations. Negative influences are side effects of
      medical treatments, the appearance of occupational, and certain recreational
      diseases. These are the pathologic effects of man's life-style to which car
      accidents, smoking and other factors can be added. Different species are affected
      by environmental changes such as pollution, ozone, acidic rain, polluted food,
      and transmission of different diseases from one species to another. Interspecies
      specifically the direct influence of man in the extermination of other species,
      or the indirect influence such as through pollutants in the environment producing
      chain reactions in different species, can be distinguished. The physical
      environment has been changed as can be seen in air pollution in large cities, the
      damage to the ozone layer and the increase of malignant melanoma in certain
      regions of western Australia. The industrialized nations are dominated by non
      infectious diseases such as atherosclerosis and neoplasms, whereas in the
      developing nations parasitic and infectious diseases stand in the fore-front.
      Particular diseases like acquired immunodeficiency syndrome increase in both
      types of nations. These diseases may have developed from other species, e.g. the
      plague which was originally a disease of rodents, especially rats where it was
      transmitted by the flea, Xenopsylla cheopis, Rothschild. The principle of
      foremost importance is the disruption of biologic integration of normal processes
      leading to different types of pathologic progression. A typical problem affecting
      man and many other fellow species is crowding. Man's pathology and the pathology
      of other species exhibit continued integration which is the central problem for
      understanding diseases where similar functions are performed by various
      structures, such as is the case in gaseous exchange, or differences in size and
      life span. The broad spectrum of comparative pathology which centers around human
      pathology provides a source of increased knowledge for a better understanding of
      diseases. The present issue is based on the two symposia organized by the
      International Society for the Study of Comparative Ongology during the Fifth
      International Conference of Anticancer Research, 17-22 October 1995, Corfu,
      Greece.

PMID- 8744791
TI  - Catabolic factors in cancer cachexia.
AB  - A lipid mobilizing factor has been purified from a cachexia-inducing mouse colon
      adenocarcinoma (MAC16) using a combination of ion exchange (Mono Q), exclusion
      (Superose) and reverse phase hydrophobic chromatography. The purification process
      led to a 3,500-fold increase in the specific activity. Serum from mice bearing
      the MAC16 tumour contained antibodies reactive with fractions containing lipid
      mobilizing activity and detectable as a 24 kDa immunoreactive band on Western
      blotting. Serum from mice transplanted with a related tumour, MAC13, not
      producing cachexia, did not contain antibodies. A similar immunoreactive band was
      detectable in the urine of patients with cancer cachexia, but was absent from the
      urine of normal subjects. A monoclonal antibody produced by fusion of splenocytes
      from mice bearing the MAC16 tumour with mouse Balb/c myeloma cells attenuated the
      development of cachexia in mice transplanted with the MAC16 tumour and inhibited
      tumour growth. These results suggest that the M(r) 24 kDa antigen may be
      important in tumour growth and cachexia.

PMID- 8744792
TI  - Breast cancer; tumor neovasculature and the effect of tissue inhibitor of
      metalloproteinases-1 (TIMP-1) on angiogenesis.
AB  - Microvessel density has been proposed as a prognostic factor in breast carcinoma.
      In paired samples of human breast carcinoma and the adjacent non-neoplastic
      tissue, proliferating microvessels were associated with in situ ductal and
      lobular carcinomas. In invasive carcinomas, the microvessels were located within
      the tumor stroma. Recombinant tissue inhibitor of metalloproteinases-1 (rTIMP-1)
      was produced in a baculovirus system to examine its effect on angiogenesis. When
      present as a molecule of 29 kDa, rTIMP-1 inhibited matrix metalloproteinase (MMP)
      activity. However, a 66 kDa aggregate of TIMP-1 did not block MMP activity,
      although it inhibited in vitro angiogenesis as the 29 kDa form did. Studies have
      been initiated to characterize the effects of overexpression of TIMP-1 on breast
      carcinoma cells. Preliminary findings show TIMP-1 mediated changes in morphology
      and downregulation of MMP activity. These findings suggest that the angiogenesis
      inhibitory activity of TIMP-1 is unrelated to its antimetalloproteinase activity
      and that TIMP-1 may affect cellular function in different ways.

PMID- 8744793
TI  - Dietary heterocyclic amines as potential human carcinogens: experimental data
      from nonhuman primates.
AB  - During the cooking of meats, several highly potent mutagenic heterocyclic amines
      (HCAs) are produced. To date, 10 HCAs have been shown to be carcinogenic in
      rodents, and one HCA, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), has been
      shown to be a potent hepatocarcinogen in nonhuman primates. In this report, we
      discuss the role of metabolic activation and DNA adduct formation in the
      carcinogenicity of HCAs, especially in nonhuman primates. The potent
      hepatocarcinogenicity of IQ in cynomolgus monkeys appears to be associated with
      the in vivo metabolic activation of IQ and the formation of hepatic DNA adducts.
      Notably, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx), is poorly
      metabolically activated in monkeys and lacks the potency of IQ to induce
      hepatocellular carcinoma. Ongoing studies with 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP), indicate that PhlP is metabolically
      activated in monkeys and is a likely carcinogen in this species. We further
      compared human, rat, and cynomolgus monkey hepatic microsomes for their abilities
      to metabolically activate various HCAs to mutagens. Our in vitro results show
      that humans, relative to rats or cynomolgus monkeys, have a good capacity to
      metabolically activate the HCAs. These findings support the concept that humans
      are likely to be susceptible to the carcinogenic effects of HCAs.

PMID- 8744794
TI  - The role of calcium in the regulation of invasion and angiogenesis.
AB  - The complex process of invasion and metastasis is now being dissected at the
      level of cell-cell and cell-substratum signaling. New tools are being developed
      to facilitate these studies. These tools include mechanisms for the investigation
      of cellular actions, such as the identification of agents that can be used to
      examine the signaling pathways involved in adhesion, proteolysis, motility, and
      angiogenesis. We have demonstrated that CAI, carboxyamido-triazole, selectively
      inhibits calcium uptake, stimulated or basal, and thereby modulates the elements
      involved in invasion and angiogenesis. Through modulation of cellular calcium
      balance, CAI secondarily inhibits calcium-dependent signaling pathways, such as
      release of second messengers, protein phosphorylation and gene transcription. We
      have demonstrated that CAI treatment resulted in inhibition of endothelial cell
      adhesion, migration, expression of proteolytic enzymes, and vessel formation in
      vitro and in vivo. The process of endothelial cell adhesion and spreading on
      extracellular matrix substrata results in an increase in intracellular calcium
      that can be inhibited by CAI exposure. Furthermore, endothelial cell adhesion and
      spreading on type IV collagen stimulates the secondary signaling events of
      tyrosine phosphorylation of focal adhesion kinase (pp125FAK) and
      autophosphorylation of pp125FAK. CAI treatment of the endothelial cells inhibited
      cell spreading, and both the induction of pp125FAK phosphorylation and the
      phosphorylation of exogenous substrates by pp125FAK kinase. These data indicate
      that regulation of cellular events key in the process of angiogenesis may be
      modulated by intracellular calcium balance thereby creating a new therapeutic
      target for anticancer research. CAI is in phase I clinical trial for patients
      with advanced cancers, yielding plasma concentrations in the in vitro anti
      angiogenic range.

PMID- 8744795
TI  - Microbial induced hemocytic immune reactions in chilopods.
AB  - Hemocytic immune reactions were investigated in the chilopod myriapods
      Scolopendra cingulata and Lithobius forficatus. Hemocytes were taken into cell
      culture medium and challenged with latex beads, pre-fixed rat erythrocytes, or
      bacteria. After 1 to 4 hours in vitro hemocyte preparations were processed for
      electron microscopy. All tested particles were phagocytosed by the hemocytes and
      where possible degrated. In both animals the phagocytic cells inside the nodules
      were found to be tightly encircled by neighboring hemocytes. Aggregation of
      hemocytes and nodule formation significantly varied with the nature of the
      particles added. Bacteria stimulated nodules were larger, more compact and more
      regular in shape than aggregations formed in the presence of latex beads or fixed
      erythrocytes. The results are discussed with respect to investigations on
      cytokines, attraction factors and gap junctions in other invertebrates.

PMID- 8744796
TI  - Racial comparison of p53 alterations in breast cancer: difference in prognostic
      value.
AB  - A significant difference in breast cancer survival between blacks and whites has
      been observed in the United States. Biological variation between races has been
      suggested to explain the difference. We investigated the difference by comparing
      the prognostic value of p53 alterations (mutations and protein accumulation)
      between black and white breast cancer patients. Black, but not white, patients
      with p53 mutations had a significantly poorer survival than those without p53
      mutations (p < 0.05). In contrast, white, but not black, patients having tumors
      with p53 protein accumulation tended to have a poorer survival than those without
      accumulation of p53 protein (p = 0.058). Among patients who died of breast
      cancer, blacks were often to have p53 mutations without protein accumulation, and
      whites frequently had p53 protein accumulation without mutations. The racial
      disparities in the associations of p53 alterations with breast cancer survival
      could have clinical implications in terms of treatment management.

PMID- 8744797
TI  - PCNA--a cell proliferation marker in vocal cord cancer. Part II: Recurrence in
      malignant laryngeal lesions.
AB  - Laryngeal squamous cell carcinoma constitutes the most frequent carcinoma found
      in the head and neck region. A precise prediction for recurrence potential cannot
      be done on site, treatment and histologic grading. Since Proliferating Cell
      Nuclear Antigen (PCNA) and DNA-cytometry have shown a good correlation between
      premalignant lesions and their progressive potential towards full-fledged
      carcinoma in the larynx as described in part I of this work, we have analyzed the
      PCNA index and DNA cytometry in specimen taken from vocal chord carcinomas with a
      5-year follow-up, in order to assess its relationship with the presence or
      absence of tumour progression. 42 cases with (21) and without (2) recurrence have
      been examined. The DNA-index ranged from 1.01 to 1.43 (mean 1.10) in the group
      without and from 1.02 to 1.59 (mean 1.38) in the group with recurrent carcinoma
      (p = 0.002). The PCNA-index ranged from 0.00% to 18.90% (mean 6.97%) in the
      nonrecurrent group and from 0.00 to 3g.50% (mean 16.35%) in the patients with
      recurrence (p = 0.001). Both indices also correlated in a highly significant way.
      From these data emerges a highly significant correlation between the cytometric
      indices of cell proliferation and PCNA immunostaining. Furthermore the high
      correction between PCNA and DNA-index is of special interest for single case
      assessment. High DNA aberration and PCNA-index in vocal chord carcinoma may
      indicate a higher cellular aggressiveness of the tumour, resulting in a greater
      overall risk of metastases and local recurrences. Our results support the thesis
      that the indices of cellular proliferation within some cancers can define subsets
      of patients of high risk and help in isolating a population in which a more
      aggressive clinical protocol may be proposed.

PMID- 8744798
TI  - Tumor induction and tumor regression in Xiphophorus.
AB  - Spontaneous melanoma in hybrids of Xiphophorus is caused by overexpression of the
      receptor tyrosine kinase gene Xmrk. In rare cases melanoma also occurs in non
      hybrid fish from natural habitats where the trigger is unknown. In these tumors
      Xmrk is overexpressed too, pointing to a similar molecular mechanism underlying
      neoplastic transformation. After carcinogen treatment a variety of tumor of other
      histiotypes are induced. Tumor genes other than Xmrk seem to cause these
      neoplasias. Genetic alterations have been detected in a recently isolated mutant,
      and immunomodulators, and androgens can cause regression of hybrid melanoma. The
      variety of etiologies and the multiplicity of exogenous factors and agents that
      induce cancer or modify the neoplastic phenotype allow the study in Xiphophorus
      of many of the problems of tumorigenesis found in vivo.

PMID- 8744799
TI  - Oncogene signal transduction inhibitors from medicinal plants.
AB  - Signal transduction is believed to be altered by cellular oncogenes or tumor
      suppressor genes during the transformation of normal cells into malignant cells.
      This proposition offers an attractive target for oncogene-based anticancer drug
      discovery from natural sources. Protein kinases encoded or modulated by oncogenes
      were used to prescreen the potential antitumor activity of medicinal plants.
      Protein-tyrosine kinase-directed fractionation and separation of the crude
      extracts of Polygonum cuspidatum and Koelreuteria henryi have led to the
      isolation of three different classes of protein-tyrosine kinase inhibitors,
      anthraquinone, stilbene and flavonoid. The anthraquinone inhibitor, emodin,
      displayed highly selective activities against src-Her-2/neu and ras-oncogenes.

PMID- 8744800
TI  - Curative effect of split low dosage total-body irradiation on murine AIDS induced
      by Friend virus: the results and the possible mechanism.
AB  - Mice infected with Friend Leukemia Virus (FLV) rapidly develop erythroleukemia
      and severe immune deficiency which resembles human AIDS. We have reported that
      mice infected with a lethal dose of FLV can be 100% cured by 150 cGy total body
      irradiation (TBI). This curative effect was associated with restoration of
      cellular immunity which was compromised by the virus. This restoration may result
      from activation of the IFN-gamma system and IL-2 production. Our research work
      further demonstrated that no spleen focus-forming virus (SFFV) specific mRNAs, no
      6.0kb SFFV fragments and SFFV envelope glycoproteins were detectable in FLV
      infected mice treated with low dose TBI. Predicated on our report, del Regato has
      initiated clinical trials to treat AIDS patients with low dose TBI. The
      preliminary results are encouraging and the study is continuing. We have also
      studied the effects of low dose TBI on the expression of the P53 gene. The
      results show loss or inactivation of P53 tumor suppressor genes in FLV-infected
      mice, but P53 expression was restored in FLV-infected mice treated by low dose
      TBI. It is intriguing to speculate that in the curative effect of low dose TBI on
      mice infected with retrovirus, the P53 tumor suppressor gene may play an
      important role. It would be of interest to see if this type of treatment, which
      was well tolerated by mice, would be beneficial in other types of virally induced
      disease, including AIDS.

PMID- 8744801
TI  - Naturin: a potent bio-immunomodifier in experimental studies and clinical trials.
AB  - A number of traditional Chinese medicinal herbs have become extremely interesting
      in the search for potential BRMs in the international medical community,
      especially in the United States and Japan. Naturin, a new Chinese medical herb
      produced by XingYa Pharmaceutical Co., Ltd., has enhanced immune response,
      inhibited tumor metastases and retroviral infection in animal models as well as
      in clinical studies. The results demonstrated that the inhibition of Natural
      Killer (NK) and Lymphokine-activated Killer (LAK) cell activity and lymphocyte
      proliferation was compromised by tumor metastases and retrovirus infection
      (Murine AIDS), even immunosuppression induced by surgical amputation can be
      restored by Naturin. It is also shown that Naturin can protect the mice from
      lethal total body irradiation. These studies indicated that Naturin possesses
      immunomodulatory effects in vivo for a broad range of stresses. The results of
      the clinical studies on Naturin have demonstrated: (a) significantly improved
      symptoms of patients, including MDS, acute and chronic leukemia, aplastic anemia,
      lung cancer, and association with the increased number and percentage of CD4
      (Helper T-cell) which have been reduced in some patients, (b) Lymphocyte
      proliferation and NK cell activity which were suppressed in cancer patients can
      be significantly restored by Naturin treatment, (c) the addition of Naturin
      treatment to patients receiving radiotherapy and chemotherapy augments immune
      response and reduces radiation and chemotherapy injury, and (d) no cytotoxic side
      effects were found in patients given Naturin treatment for up to eight months.

PMID- 8744802
TI  - Functional analysis of Drosophila developmental genes instrumental in tumor
      suppression.
AB  - Of the 28 presently known Drosophila tumor suppressor genes we present the status
      of the functional analysis of the following three genes: (a) lethal (3) malignant
      brain tumor [1(3)mbt], which by homology belongs to the Pc-G gene family and may
      be involved in the stable silencing of specific developmental genes by changing
      the chromatin structure, and thus establishing and maintaining the differentiated
      state; (b) lethal (3) malignant blood neoplasm-1 [1(3)mbn-1], for whose function
      only vague predictions can be made; 4) benign (2) gonial cell neoplasm [b(2)gcn],
      which may function as a splice factor. Each Drosophila tumor suppressor gene
      transforms in the homozygously mutated state either one or two specific cell
      types in a single step, and is thus the primary cause for tumorigenesis. For one
      of the genes a putative human homologue has been found.

PMID- 8744803
TI  - Relationship between c-erbB-2 oncoprotein, epidermal growth factor receptor, and
      estrogen receptor expression in patients with ductal breast carcinoma.
      Association with tumor phenotypes.
AB  - The expression of c-erbB-2 oncoprotein, epidermal growth factor receptor (EGFR)
      and estrogen receptor (ER) was evaluated by the immunoperoxidase technique (PAP)
      in ductal breast carcinomas. The relationship between these cell growth
      regulatory factors was considered and compared with tumor grading, tumor size,
      lymph node involvement and age of patients. Stratifying of patients on the basis
      of c-erbB-2, EGFR and ER status indicated that the combination of c-erbB-2
      overexpression accompanied by high EGFR value and undetectable ER, identified
      poorly differentiated tumors and patients with high incidence of axillary lymph
      node metastases, while high EGFR expression and negative c-erbB-2 staining was
      connected only with poor tumor grade. The undetectability of molecular markers
      was associated with higher histological grade and lack of lymph node involvement.
      Our results indicate that the comparison of c-erbB-2, EGFR and ER status seems to
      be a powerful tool in discriminating breast carcinomas with different biological
      phenotypes.

PMID- 8744804
TI  - The retinoblastoma gene: its role in cell cycle and cancer.
AB  - The retinoblastoma gene is the prototype of the tumor suppressor genes, which
      play critical roles in the genesis of cancer in humans. Although the precise
      function of the retinoblastoma gene product remains unknown, recent data suggests
      that it plays dual roles in gating cell cycle progression and promoting cellular
      differentiation. The molecular mechanisms involved in these roles are becoming
      clear in some biological systems: pRb binds and sequester several transcription
      factors to regulate entry of cell cycle and to initiate terminal cellular
      differentiation. However, it is difficult to rationalize the expression of pRb in
      a wide range of tissues with the fact that only limited cell types are
      susceptible to tumor formation when Rb expression is lost. Recent
      characterizations of Rb-associated proteins may provide some clues as to how Rb
      function may be differentially modulated in a cell type-specific manner.

PMID- 8744805
TI  - Recovery and characterization of CD34+ cord blood cells after cryopreservation.
AB  - Hematopoietic stem and progenitor cell transplantation is an important therapy
      for certain hematological and malignant disorders, and these cells are being used
      as vehicles for potential gene therapy approaches to treatment. Umbilical cord
      blood is a rich source of stem and progenitor cells, which can be efficiently
      transduced by viral vectors with new genetic material, and these cells have been
      used in both allogeneic and autologous transplant settings, the latter setting
      used by others for gene transfer as a possible means of gene therapy. Since cord
      blood banking is increasingly being considered as an adjunct for allogeneic and
      autologous transplantation, the present studies were done in order to evaluate
      the consequences of cryopreserving highly purified CD34+ cells from cord blood.
      The results demonstrate that CD34+ cord blood cells can be frozen in
      cryopreserved form and recovered efficiently with cell cycle, proliferative and
      cell expansion characteristics equivalent to the pre-freeze samples of cells.
      This information complements previous studies from our group demonstrating the
      efficient freezing of relatively unseparated populations of cord blood cells, and
      should be of practical use for future studies involving banking and use of cord
      blood stem and progenitor cells.

PMID- 8744806
TI  - Gastric carcinoma in African Americans: a 10 year single center analysis.
AB  - The occurrence of gastric cancer (GCa) has been declining in the U.S. over the
      past years. The reasons for this decline, though unclear, may not hold true for
      minorities. In fact, data on the occurrence, presentation and determinants of
      survival in African Americans still remains sketchy. In an attempt to rectify
      this problem, we retrospectively analyzed accumulated data at the Howard
      University Cancer Center between 1985 and 1994. There were 115 patients with GCa,
      53 females and 62 males. The age range was 26-88 years, with most patients being
      over 50 years of age (84%). Eighty seven out of the 115 patients were completely
      staged and thus formed the population base for the analysis. There was a
      progressive decline in the frequency of diagnosis of GCa between the 1985-1989:
      63% cases (55/87) and 1990-1994: 37% cases (32/87). In analyzing this group, we
      found no gender difference on presentation. Seventy percent of the patients
      (61/87) presented with the advanced disease (stages III & IV). Eighty eight
      percent (77/87) underwent surgery: 50/77 surgery alone; 9/77 surgery and chemo;
      18/77 surgery and other forms of therapy (radiotherapy and chemotherapy). Seventy
      one percent of the patients who presented with late stage disease, died within 12
      months. The predominant histologic type was adenocarcinoma (85%), while lymphoma
      and leiomyosarcoma accounted for five and three percent respectively. In
      conclusion, our data suggest that most patients in our minority population
      presented at a late stage of GCa, and stage was an important determinant of
      survival. Also, our findings are in agreement with the declining trend of GCa in
      the U.S.

PMID- 8744807
TI  - Post-transplant malignancies in minority populations.
AB  - Post-transplant malignancy (PTM), is emerging as an important cause of early
      morbidity and mortality following transplantation (TX). Unfortunately its
      prevalence in minorities (African-Americans, AA; Native Americans, NA; Asian
      Pacific Islanders, AP; American Indians, AI; Latino-Hispanics, LH) in the United
      States, though important, remains unknown. Published reports of prevalence rates
      by different centers, including the Cincinnati Transplant Tumor Registry (CITTR)
      of about 4%-18% though informative, remain of little help. These reports
      erroneously assume a homogeneity in population, uniformity in the impact and
      spread of the determinants of this disease, and equal access to health for all
      patients. Data from AA, the only minority group studied by the Howard University
      Hospital Transplant Center (HUHTC) group, in Washington, D.C.; revealed a cancer
      occurrence of 3% in 339 TX patients. It is important to note that unlike the
      CITTR data base, the HUHTC cancer database is smaller. Nevertheless, a
      comparative analysis was revealing. Skin/lymphoid cancers had a lower occurrence
      (20% versus 54%), while head and neck tumors had a higher occurrence (30% versus
      3%) as were genitourinary cancers (30% versus 8%) in AA as compared to the
      general population. Since minorities as a group are prone to higher cancer
      prevalence and mortality rates, and because patterns of PTM may differ among
      groups, studies to analyze PTM and other factors that may further escalate cancer
      rates in minorities deserve greater impetus.

PMID- 8744808
TI  - Splenectomy in cancer surgery: diminishing indications?
AB  - The diminishing enthusiasm towards performing splenectomy (SPL) either as an
      integral part of surgical cancer management (SCM), or for staging/management (ST)
      of lymphoma, warranted our assessment of the extent of this trend in a minority
      population. We retrospectively analysed all SPL submitted to Surgical Pathology
      for histological processing over a 24-year period (1/1/70-12/31/93) at the Howard
      University Hospital, a predominantly African-American institution. Of the 446 SPL
      performed during the period, sixty-nine (15.5%) were performed as part of SCM/ST.
      Seventy-five per cent (52/69) were for solid intra-abdominal cancers (SIC) and
      25% (17/69) for lymphoma. As a group, the patients were older, 71% over 40 years
      old) and showed a male predominance (61% males). Sixty-two per cent (43/69) of
      the SPL were performed in the decade 1970-1979. In the following decade 1980
      1989, the frequency with which SPL was performed, had dropped to 33% (23/69).
      Four years into the current decade, 1990-1993, only 5% (3/69) of the SPL were
      performed for SCM/ST. These findings suggest that in African-Americans, the
      performance of SPL in ST/SCM has been declining over the years, which is in
      agreement with the current growing trends in cancer treatment i.e. to avoid
      unnecessary operations, limit morbidity, preserve important organs, maintain
      immunocompetence of the patient and to utilize advanced imaging techniques in
      ST/SCM.

PMID- 8744809
TI  - The thyroid gland as an intrinsic biologic response-modifier in advanced
      neoplasia--a novel paradigm.
AB  - The thyroid gland is the major endocrine modulator of physiological processes
      crucial to growth, maturation and metabolism. There is, however, a coherent body
      of evidence suggesting that the thyroid hormones modulate multiple neoplasia
      dependent mechanisms. Recently spontaneous remission of metastatic non-small cell
      carcinoma of lung was reported in a man following recovery from myxedema coma.
      This rare biological event following a life-threatening clinical syndrome
      suggests that thyroid hormone deficiency directly or indirectly may significantly
      alter the balance between malignant tumor viability and growth on the one hand
      vs. cell death on the other. Evidence, therefore, is presented from clinical and
      experimental studies suggesting that decreased thyroid function (hypothyroidism)
      is associated with both enhanced response rates and unusual longevity. Possible
      mechanisms of action that may promote or retard neoplasia and are dependent on
      the functional state of the thyroid will be discussed. A novel paradigm is
      proposed; the thyroid gland aside from its known physiological activity is also
      the central modulator of solid neoplasia and therefore functions as an intrinsic
      biologic response-modifier of neoplasia. Induction of a clinically tolerable
      hypothyroid state in patients could become an integral part of the medical care
      of advanced cancer in conjunction with standard conventional modalities.

PMID- 8744810
TI  - Crowding.
AB  - Crowding is the situation in which case a large number of animals, including man,
      are restricted in environmental space. Such an occurrence may start with just a
      few animals. In plants, including bacteria in culture, agriculture may be
      considered as an artificial example of this process. We see the ontogenic forms
      of crowding developing from stress into superorganisms (such as certain social
      insects) and from stress into pathological crowding in animals, plants and man.
      Crowding is shown by environmental changes such as in the introduction of new
      species of certain rodents and lagomorphs into the Australian environment.
      Aspects of crowding play a role during the housing of zoos, domestic or
      laboratory animals. Space limitations and overpopulation initiates stress and
      infections such as tuberculosis and tumours. This is found in man himself in the
      development of slums through to urbanisation as seen in Asia particularly, in
      prisons, in the workplace, in the school or home.

PMID- 8744811
TI  - Economic costs of neoplasms, arteriosclerosis, and diabetes in the United States.
AB  - Substantial economic resources are used for treatment of neoplasms,
      arteriosclerotic diseases, and diabetes (direct costs), and substantial
      productivity is lost due to morbidity and mortality (indirect costs). Costs of
      these disease groups in the U.S. in 1993 are estimated from national health
      expenditures from the Health Care Financing Administration and survey data from
      the National Center for Health Statistics. Based on primary diagnosis, direct
      costs are $37 billion for neoplasms, $126 billion for arteriosclerosis, and $15
      billion for diabetes, and indirect costs are $70, $83, and $5 billion
      respectively. Costs would be higher, particularly for diabetes ($92-138 billion),
      if based on primary and secondary diagnosis.

PMID- 8744812
TI  - Marketing and commercial challenges for anticancer products.
AB  - Traditional marketing techniques that are employed by pharmaceutical
      manufacturers are not adequate in the oncology setting. Many unique
      characteristics of this therapeutic area create challenges to the marketing and
      sales teams responsible for selling anticancer and cancer-therapy support
      products. There is a high burden on those marketing oncology products to provide
      vast amounts of information about their products, in a timely manner, to various
      groups of health care providers, while functioning within established legal
      boundaries. Pharmaceutical companies, through their sales and marketing efforts,
      are working to provide the information health care providers need to make patient
      management decisions and prevent the health care environment from restricting
      physician and patient choices.

PMID- 8744814
TI  - Imaging of atypical choroid plexus papillomas.
AB  - The authors report a rare case of benign choroid plexus papilloma arising in the
      cerebellopontine angle (CPA) in a 34-year-old man. Atypical features are
      described. This is the fourth case of MR evaluation of such tumor in available
      literature and the second case in the United States. Differential diagnosis is
      discussed. Choroid plexus papilloma should be considered among calcified,
      vascular, enhancing masses of CPA even in adulthood. The authors also report an
      unusual case of choroid plexus carcinoma.

PMID- 8744813
TI  - Diagnosis of spinal arteriovenous malformations by MRI at 1.0 T.
AB  - Eight patients were examined by magnetic resonance imaging (MRI) at 1.0 T; seven
      had an angiographically proved spinal intradural arteriovenous malformation and
      one had a hemangioblastoma of the spinal cord. Myelography was also performed in
      five and computed tomography (CT) in four patients. The clinical and radiological
      findings are presented. MRI revealed the location and extent of the lesion.
      Myelomalacia, edema, and hematomyelia were demonstrated in three patients. In our
      opinion MRI is the method of choice for the diagnosis of spinal arteriovenous
      malformation and facilitates spinal angiography, whereas myelography and CT do
      not provide any further information.

PMID- 8744815
TI  - Imaging of pineal apoplexy.
AB  - The authors present 2 unusual cases of hemorrhagic pineal cysts. CT/MR imaging
      characteristics are shown.

PMID- 8744816
TI  - Spontaneous pulsatile tinnitus secondary to a dural malformation not visualized
      by magnetic resonance angiography.
AB  - The author describes a case of tinnitus secondary to a right dural malformation
      not visualized by magnetic resonance angiography. The prime role of computed
      tomography/angiography is emphasized.

PMID- 8744817
TI  - Multifocal angiomyolipoma in a patient with tuberous sclerosis.
AB  - Angiomyolipomas are rare lesions that occur most commonly in the kidney, but also
      can occur in the liver and rarely, in the lymph nodes. Its rare association with
      tuberous sclerosis has been suggested, but never proved. We report a patient with
      multiple visceral angiomyolipomas as well as visceral vessel aneurysms and
      tuberous sclerosis. The association of the three lesions suggests a possible
      common connective-tissue defect.

PMID- 8744818
TI  - Systemic venous enhancement patterns during dynamic abdominal CT.
AB  - In 25 patients we assessed the enhancement of abdominal venous structures during
      dynamic computed tomography (CT). The degree of venous enhancement demonstrated
      great variation. In six instances (out of 250 observations) a vessel was visually
      perceived as not enhancing and potentially thrombosed, including three gonadal
      veins. CT measurements were helpful in identifying enhancement, but were
      occasionally low enough that thrombosis remained a radiological consideration.
      The great variation in venous enhancement makes the diagnosis of thrombosis
      suspect, based on CT alone. Corroboration of this finding is suggested, when
      clinically relevant.

PMID- 8744819
TI  - An unusual presentation of Zenker's diverticulum.
AB  - Zenker's diverticula are esophageal outpouchings in the region of the
      cricopharyngeus which typically grow in a posterolateral and inferior direction
      and can cause esophageal compression if the diverticulum is large enough. We
      describe a patient in whom a Zenker's diverticulum expanded posteriorly and
      superiorly so that it was positioned in the posterior pharyngeal space, causing
      both esophageal and tracheal narrowing.

PMID- 8744820
TI  - Septic thrombophlebitis of the inferior mesenteric vein associated with
      diverticulitis CT diagnosis.
AB  - Septic thrombophlebitis of a mesenteric vein can occur as a rare complication of
      diverticulitis. We report a case of septic thrombophlebitis of the inferior
      mesenteric vein diagnosed with computed tomography, in a patient with sigmoid
      diverticulitis.

PMID- 8744821
TI  - Dynamic gadolinium-DOTA-enhanced MR imaging at 1.0 T. Value in the
      differentiation of hepatic tumors.
AB  - A prospective study was performed to determine the value of dynamic gadolinium
      tetraazacyclododecane-tetraacetic acid (Gd-DOTA)-enhanced magnetic resonance (MR)
      imaging at 1.0 T, using a gradient-echo (GRE) technique, in the differentiation
      of hepatic tumors. Fifty patients with hemangiomas (n = 14), focal nodular
      hyperplasia (n = 4), and malignant tumors of the liver (n = 32) underwent GRE MR
      imaging at 1.0 T before and repeatedly for 4 minutes after intravenous bolus
      administration of Gd-DOTA. The diagnoses were proved by histology or follow-up
      examination. On unenhanced GRE images, hemangiomas had a significantly lower
      tumor-to-liver contrast-to-noise (C/N) ratio (-14.74 +/- 4.49) than did the other
      tumors (-6.96 +/- 5.49) (p < 0.02), and benign tumors had a significantly lower
      C/N ratio (-12.43 +/- 5.99) than did malignant tumors (-7.29 +/- 5.71) (p <
      0.05). On contrast-enhanced images, hemangiomas had a significantly lower C/N
      ratio (-17.60 +/- 6.90) than did the other tumors (-5.07 +/- 12.12) (p < 0.05) in
      the early phase. During the delayed phase, hemangiomas had a significantly higher
      C/N ratio (3.90 +/- 3.81) than did the other tumors (-4.85 +/- 6.51) (p < 0.01),
      and benign tumors had a significantly higher C/N ratio (3.21 +/- 3.65) than did
      malignant tumors (-5.56 +/- 6.56) (p < 0.001). Our data suggest that dynamic Gd
      DOTA-enhanced MR imaging at 1.0 T provides useful information to differentiate
      between benign and malignant hepatic tumors, and to distinguish hemangiomas from
      the other tumors.

PMID- 8744822
TI  - MR imaging of primary adrenal lymphoma.
AB  - We describe a patient with non-Hodgkin's B-cell lymphoma of diffuse large cell
      type, which involved both adrenal glands without adrenocortical insufficiency.
      Magnetic resonance showed bilateral adrenal tumors with some enhancing septa.

PMID- 8744823
TI  - Primitive mucinous cystadenocarcinoma of the retroperitoneum. Case report and
      diagnostic considerations.
AB  - The combination of ultrasonography (US) and computed tomography (CT) proved
      useful in recognizing and defining the characteristics of a primitive mucinous
      cystadenocarcinoma of the retroperitoneum, a rare anatomopathological finding
      which consistently presents certain macroscopic features that help in the
      formulation of a diagnosis with imaging techniques.

PMID- 8744824
TI  - Retroperitoneal actinomycosis with intraperitoneal spread. Stellate pattern on
      CT.
AB  - We report a case of pathologically proved actinomycosis that presented unusual
      computed tomographic (CT) features: a soft-tissue retroperitoneal mass encasing
      the adjacent ureter resulting in hydronephrosis and spreading into the
      intraperitoneal space with a stellate pattern. The role of CT in monitoring the
      response to antibiotic treatment is also discussed.

PMID- 8744825
TI  - Malignant vaginal melanoma. Usefulness of fat-saturation MRI.
AB  - We present a case of malignant vaginal melanoma studied by magnetic resonance
      imaging (MRI). A dark irregular mass was noted in the anterior wall of the
      vaginal cavity on physical examination. On fat-saturated T1-weighted MRI, the
      vaginal lesion was demonstrated more clearly than by conventional T1- and T2
      weighted images. Furthermore, the fat-saturated image detected the bladder
      metastasis from the vaginal lesion.

PMID- 8744826
TI  - Cerebrospinal fluid flow artifact. A possible pitfall on fast-spin-echo MR
      imaging of the spine simulating intradural pathology.
AB  - We have noted that fast-spin-echo T2-weighted images of the cervical and thoracic
      regions of the spine can produce low-signal artifacts in the spinal subarachnoid
      space which might be misinterpreted as tumor or abnormal vascular flow voids.
      These are possibly related to complex cerebrospinal fluid pulsatile flow and
      should be recognized as artifactual by the radiologist.

PMID- 8744827
TI  - A 40-year-old woman with back pain.

PMID- 8744829
TI  - Transmembrane domains participate in functions of integral membrane proteins.
AB  - Integral membrane proteins have one or more transmembrane alpha-helical domains
      and carry out a variety of functions such as enzyme catalysis, transport across
      membranes, transducing signals as receptors of hormones and growth factors, and
      energy transfer in ATP synthesis. These transmembrane domains are not mere
      structural units anchoring the protein to the lipid bilayer but seem to
      contribute in the overall activity. Recent findings in support of this are
      described using some typical examples-LDL receptor, growth factor receptor
      tyrosine kinase, HMG-CoA reductase, F0-ATPase and adrenergic receptors. The
      trends in research indicate that these transmembrane domains participate in a
      variety of ways such as a linker, a transducer or an exchanger in the overall
      functions of these proteins in transfer of materials, energy and signals.

PMID- 8744828
TI  - Light signal transduction mediated by phytochromes: preliminary studies and
      possible approaches.
AB  - Phytochromes mediate a variety of developmental and growth processes involved in
      the photomorphogenesis of plants. In this article, we review the current
      understanding of the structure and function of the photoreceptor, discuss some
      very preliminary results, and offer speculations and even conjectures that may
      elicit future studies into the molecular mechanisms of the phytochrome-mediated
      light signal transduction in plants.

PMID- 8744830
TI  - Glutamate transfer RNA: a cofactor for heme and chlorophyll biosynthesis.

PMID- 8744831
TI  - Estimation of single-strand breaks induced in the dried film of DNA by high
      energy alpha particle from a cyclotron.
AB  - DNA extracted and purified from Vibrio cholerae OGAWA 154 cells and prepared in
      the form of a dry thin film was exposed in air to a beam of alpha particles
      obtained from a Variable Energy Cyclotron. The number of single-strand breaks per
      DNA unit exhibited a linear dose-effect relationship indicating the occurrence of
      single-hit kinetics. The efficiency and yield of alpha-induced single-strand
      breaks were approximately 72 eV/break and 1.39 respectively.

PMID- 8744832
TI  - Kinetics of adsorption of denatured protein at alumina-water interface.
AB  - The kinetics of adsorption of soluble denatured protein, gelatin has been studied
      at the alumina-water interface as a function of protein concentration, pH,
      temperature and ionic strength. The rate of adsorption of gelatin has been
      compared with rate of adsorption of BSA denatured by 8 M urea or 0.05 M SDS. The
      initial stage for the adsorption process is diffusion-controlled and the surface
      diffusion coefficients evaluated from equations of Ward and Tordai and by Bull
      for globular and denatured proteins are found to be widely different from each
      other. The kinetic data for gelatin fit into a first order rate equation with two
      rate constants, k1a and k2a. Using Arrhenius equation, the activation energies
      delta E1* and delta E2* have been evaluated from the values of k1a and k2a
      respectively. The corresponding changes in values of enthalpy of activation
      (delta H*), entropy of activation (delta S*) and free energy of activation (delta
      G*) have been evaluated using Eyring's equation for absolute reaction rate. It
      has been found that for both gelatin and denatured BSA, in the first kinetic step
      delta H1* > T delta S1* and for the second step T delta S2* > delta H2.

PMID- 8744833
TI  - Isolation and characterization of monkey liver ferritin.
AB  - Monkey liver ferritin was isolated and purified along with human liver ferritin
      and their physicochemical and immunological characteristics were compared. The
      apparent molecular weight of monkey liver ferritin was estimated to be 430 kDa as
      against 450 kDa of human liver ferritin. Both ferritins appeared to be made up of
      a 22.5 kDa polypeptide under denaturing conditions and the proteins contained
      neutral sugar (wt/wt) of 2.0% (monkey) and 2.4% (human). By immunoblots both
      human and monkey liver ferritins showed appreciable cross-reactivity with the
      polyclonal antibodies raised against either proteins. Monkey liver ferritin,
      however, was not recognised by the human monoclonal antibody. The amino acid
      composition of both ferritins was more or less similar. Isoelectric focusing
      indicated that monkey liver ferritin showed microheterogeneity with three bands
      at pI 5.4, 5.5 and 5.6, whereas human liver ferritin showed a single band at pI
      5.6 confirming the relative acidic nature of monkey liver ferritin.

PMID- 8744834
TI  - Effect of ischemia/reperfusion on intestinal brush border membrane lipid
      composition, fluidity and enzyme activities.
AB  - Oxygen-derived free radicals are known to be generated during
      ischemia/reperfusion injury and biomembranes are the prime target of these active
      species. In order to study the effect of in vivo generated free radicals on
      intestinal mucosal membrane, brush border membranes (BBM) were isolated from rat
      small intestine after subjecting to ischemia (I) and ischemia/reperfusion (I/R)
      injury and their lipid composition and marker enzyme activity were compared with
      BBM prepared from control animals. No significant alteration in the lipid
      composition of BBM was observed after I or I/R as compared to control. Membrane
      fluidity measurements showed that I/R increased the fluidity of BBM. Activity of
      alkaline phosphatase, one of the marker enzymes for BBM was reduced by I or I/R
      whereas activity of another BBM enzyme, sucrase was not altered. The decrease in
      alkaline phosphatase activity was more after reperfusion. In vitro fluidization
      of BBM using benzyl alcohol indicated that the inactivation of alkaline
      phosphatase was not due to change in fluidity. These results suggest that free
      radicals generated during I/R inactivate BBM alkaline phosphatase partially
      without altering the membrane lipid composition.

PMID- 8744835
TI  - Protective role of anion channel blocker in lipid peroxidation caused by H2O2 in
      microsomes of bovine pulmonary arterial smooth muscle tissue.
AB  - The role of hydroxyl radical (OH.) in H2O2-mediated stimulation of lipid
      peroxidation in microsomes of bovine pulmonary arterial smooth muscle tissue and
      the protective effects of DIDS, the anion channel blocker have been studied.
      Treatment of microsomes with H2O2 (1 mM) stimulate iron release, OH. production
      and lipid peroxidation. Pretreatment with DFO (an iron chelator) or DMTU (a
      hydroxyl radical scavenger) prevents OH. production and thereby reduces lipid
      peroxidation without any appreciable reduction of iron release. Simultaneous
      treatment of either DFO or DMTU with H2O2 significantly reduces lipid
      peroxidation and prevents OH. production without any significant reduction of
      iron release. However, addition of DFO or DMTU 2 min after treatment of the
      microsome with H2O2 does not produce any significant reduction of lipid
      peroxidation, OH production and iron release. Pretreatment of microsomes with
      DIDS markedly reduces the stimulation of lipid peroxidation without appreciably
      altering the increase in OH. production and iron release caused by H2O2.

PMID- 8744836
TI  - Oxalate binding to rat kidney mitochondria: induction by oxidized glutathione.
AB  - Increased oxalate binding with negative correlation with reduced glutathione
      content was observed during lipid peroxidation in rat kidney mitochondria. In
      presence of oxidized glutathione (GSSG), peroxidized mitochondria lost 48% of
      protein-SH with concomitant 3-fold increase in oxalate binding activity while
      control mitochondria lost only 20% protein-SH with only 0.8 fold increase in
      oxalate binding activity. The GSSG-induced oxalate binding was apparently due to
      two-fold increased affinity of oxalate to the protein. Reduced glutathione (GSH)
      inhibited oxalate binding competitively with Ki, 1.4 x 10(-3) M. Urolithic rat
      kidney mitochondria showed 30-50% increase in oxalate binding activity along with
      depletion of GSH and protein-SH. These studies suggest that oxalate binding is
      regulated by thiol status of mitochondria.

PMID- 8744837
TI  - Fractionation, analysis and diagnostic utility of Mycobacterium tuberculosis
      H37Ra excretory-secretory antigen in pulmonary tuberculosis.
AB  - Excretory-secretory antigen of Mycobacterium tuberculosis H37Ra (Mtb ES antigen)
      isolated from culture filtrate was partially purified by 6% trichloroacetic acid
      precipitation. The TCA supernatant fraction (Mtb EST antigen) was examined for
      its diagnostic use in the detection of tuberculous IgG antibody in human sera by
      stick Indirect ELISA. Using Mtb EST antigen, tuberculous IgG antibody was
      detected in 90% of smear positive and 71% of smear negative pulmonary
      tuberculosis cases and 10% of healthy and disease controls. Further fractionation
      of Mtb EST antigen by SDS-PAGE yielded four active antigenic fractions viz., Mtb
      EST-3,4,6 and 10. Diagnostic evaluation of these fractions showed Mtb EST-6
      antigen fraction to be useful in detection of both smear positive and smear
      negative pulmonary tuberculosis cases with sensitivities of 94% and 78%
      respectively and specificity of 88%.

PMID- 8744838
TI  - A theoretical study of hydrophobic fragment and factor constants of Hansch and
      Leo: estimation of a few non-available fragments and factors.
AB  - Hydrophobic fragment constants (f) of benzotriazol-2-yl and Ar-N[CO-]2 systems,
      and aliphatic H/S polar interaction factors F(H/S) in Cl2CHCONH-Ar and Cl3CCONH
      Ar, of Hansch and Leo's constructionist approach, were estimated as 0.69
      (standard deviation = 0.17), -1.98, 0.95 and 0.98 respectively. The validity of
      the first constant has been tested by calculating the log P of compounds not
      included in the regression.

PMID- 8744839
TI  - Effect of two cardiac glycosides, digitoxin and digoxin on blood lipids.
AB  - Two cardiac glycosides, namely digitoxin and digoxin when treated with goat
      blood, were found to alter the lipid constitution as measured by their phosphorus
      content, fatty acid composition and malonaldehyde content. There was significant
      increase in the poly-unsaturated fatty acids (PUFA) and malonaldehyde contents in
      blood treated with these drugs. Possible correlation between the lipophilicity of
      the drugs and their biological activity is discussed.

PMID- 8744840
TI  - Cloning and characterization of mycobacteriophage I3 promoters.

PMID- 8744841
TI  - Patterns of corneal topography after penetrating keratoplasty.
AB  - BACKGROUND: The topography of corneas after penetrating keratoplasty is highly
      variable. We classify the topography into five groups. METHODS: We performed
      videokeratography on 45 clear compact penetrating keratoplasties, with all
      sutures removed. Three ophthalmologists classified the keratographs independently
      into five previously defined topographic groups, based on the pattern of the
      normalized color-coded videokeratograph. RESULTS: The five topographic patterns
      included: prolate bow tie, 14 (30%); oblate bow tie, 14 (30%); mixed prolate and
      oblate bow tie, 8 (17%); asymmetric, 3 (9%); and steep/flat, 6 (14%). The three
      ophthalmologists agreed in their initial classification in 87% of the cases and
      after discussion, in 96%. CONCLUSION: The topography of the cornea after
      penetrating keratoplasty can be classified into five qualitative groups by
      trained observers, with good clinical reliability.

PMID- 8744842
TI  - Syphilitic interstitial keratitis with bilateral funnel-shaped iridocorneal
      adhesions. A case report.
AB  - We present the clinical and light microscopic ophthalmological findings in a 60
      year-old woman with bilateral, symmetrical, paracentral anterior synechia
      formation and healed, old, inactive interstitial keratitis, probably secondary to
      congenital syphilis. The patient underwent ECCE and IOL implantation in the left
      eye and a triple procedure (corneal transplantation, ECCE and IOL) in the right
      eye. Gonioscopy, fluorescein angiography and light microscopy of a specimen from
      the triple procedure revealed a fibrovascular connection between the iris and
      cornea. The etiology of the funnel-shaped bilateral iridocorneal synechiae is
      discussed.

PMID- 8744843
TI  - Treatment of inferior oblique muscle overaction with myectomy or with anterior
      transposition.
AB  - This paper presents a comparative study of the effectiveness of myectomy and
      anterior transposition in the treatment of inferior oblique muscle overaction. We
      operated 160 patients with overaction of the inferior oblique muscle. Eighty
      patients (148 eyes) were operated by myectomy at the insertion and 80 patients
      (151 eyes) by anterior transposition of the insertion of the inferior oblique
      near the temporal side of the insertion of the inferior rectus muscle. Comparison
      of the two methods, using the chi-squared test, showed that: 1) both surgical
      procedures were equally effective (chi 2 = 0.26) for correcting overaction of the
      inferior oblique muscle and V-phenomenon; 2) weakening of the inferior oblique
      muscle of both eyes was almost always required (in 115 out of 116 cases) in cases
      with V-phenomenon and often (24 out of 44 cases) in cases of congenital paresis
      of the superior oblique muscle. We conclude that both procedures are equally
      effective and equally easy to perform.

PMID- 8744844
TI  - Erythropoietin-induced iritis-like reaction.
AB  - The present report describes an iritis-like reaction found in 13 patients treated
      with recombinant human erythropoietin (Eprex), a drug given to hemodialysis
      patients for their chronic anemia. Among 120 patients being treated by
      hemodialysis in two centers affiliated with our medical center, ten out of 30
      Eprex-treated patients but none of 90 not being treated with Eprex developed this
      reaction. The observations described support a causal relation between Eprex
      treatment and the iritis-like reaction. Further investigative effort is needed to
      establish the mechanism.

PMID- 8744845
TI  - Fixed combination of carteolol and pilocarpine eye-drops: a double-blind
      randomized cross-over trial versus carteolol alone on intra-ocular pressure. The
      Study Group.
AB  - The effects of carteolol 2% and a fixed combination of carteolol 2% and
      pilocarpine 2% (CBS 341 A) eye-drops on intraocular pressure (I.O.P.) were
      compared in a multicenter double-blind, cross-over prospective trial. Twenty
      eight patients were initially selected after at least three weeks of carteolol
      2%, with a morning I.O.P. greater than 21-mmHg. They received 2 drops a day
      (b.i.d.), in a random order, alternating two weeks of carteolol 2% alone or two
      weeks of CBS 341 A. After each two-week period a 12-h I.O.P. curve was plotted.
      Compared to carteolol the combination reduced I.O.P. on average by around 20% (4
      mmHg), with maximum effect 4h after instillation. The effectiveness was confirmed
      after twelve hours. Some side effects were reported with CBS 341 A, due to the
      well known pharmacological effects of pilocarpine. The new combination could be
      useful for second-line therapy in glaucoma.

PMID- 8744846
TI  - Preclinical safety profile of brimonidine.
AB  - Brimonidine is a selective alpha 2-adrenergic agonist developed for lowering
      intraocular pressure in glaucoma patients. Since brimonidine will be used in long
      term theraphy, the safety of this drug is an important feature for its clinical
      success. Brimonidine has been evaluated in a number of safety studies using doses
      much greater than those in humans. In this paper chronic and carcinogenicity
      studies are presented. The results of the 6-month ocular/systemic study in
      rabbits and the 1-year ocular/systemic study in monkeys with 0.2, 0.5, and 0.8%
      brimonidine ophthalmic formulations showed no ocular or organ toxicity. The
      highest concentration of 0.8% used in rabbits and monkeys resulted in plasma drug
      concentrations of 95 (Cmax) and 10 (C2hr) times, respectively, higher than those
      seen in humans following topical dosing. Dose-related transient exaggerated
      pharmacologic effects of sedation were observed in the 1-year oral study in
      monkeys without any organ toxicity. The dose that elicited an apparent
      pharmacologic effect produced a plasma drug concentration that was approximately
      115 times higher than that in humans. In 2-year carcinogenicity studies in mice
      and rats using doses that produced plasma concentrations 77 and 118 times,
      respectively, higher than those seen in humans, no oncogenic effect was observed.
      Based on the extensive safety research on brimonidine, it was concluded that this
      drug has an excellent safety profile.

PMID- 8744847
TI  - Epidemiology of glaucoma in northern Europe.
AB  - PURPOSE: To survey glaucoma epidemiology in Northern Europe. RESULTS OF
      LITERATURE REVIEW: Open-angle glaucoma is defined here as the simple and capsular
      types taken together. On this basis open-angle glaucoma makes up by far the
      largest group of glaucoma in Northern Europe. These are the target groups of this
      study, and pigmentary glaucoma is excluded because of the small numbers.
      CONCLUSION: Open-angle glaucoma is less frequent in Southern Sweden and Denmark
      than in Finland, Middle Sweden, Norway, and iceland. This may to some extent be
      explained by the suggested low prevalence of pseudoexfoliation in the southern
      areas, but other factors are presumed to be of importance as well.

PMID- 8744848
TI  - Computer assisted image analysis using the subtraction method in indocyanine
      green angiography.
AB  - The choroidal vessels are three dimensionally distributed and very complex in
      their patterns. They often appear to be overlaid in indocyanine green (ICG)
      angiograms so it is harder to analyze ICG angiography than fluorescein
      angiography. When an earlier frame is subtracted from a later frame in a sequence
      of angiograms, the fluorescence which has increased during the time between the
      two frames can theoretically be demonstrated. We applied computer-assisted image
      subtraction methods in selected clinical cases of directly acquired digital ICG
      angiography to demonstrate how this method works. We used software already
      installed in an IMAGEnet computer system (Topcon) for image subtraction. We
      applied the subtraction technique in 18 cases with various diseases. When two
      images with a time difference of several seconds were subtracted, filling of the
      choriocapillaris, the neovascularization or the pathological vessels could be
      observed. When the images had a time difference of several minutes,
      intrachoroidal dye leakage could be seen more clearly. This method is very
      helpful for analyzing pathological changes in ICG angiography in clinical cases,
      when two images are selected appropriately.

PMID- 8744849
TI  - Indocyanine green angiography (ICGA) in pathological myopia.
AB  - One hundred and fifty patients (300 eyes), mean age 49 +/- 15 years, with
      degenerative myopia underwent fluorescein and indocyanine green angiography
      (ICGA). Fluorescence of choroidal neovascularization (CNV) on ICGA was less
      evident than with fluorescein angiography (FA). FA revealed CNV in 98 eyes; ICGA
      showed CNV with different angiographic patterns in 82 eyes. ICGA permitted CNV
      diagnosis when retinal hemorrhages were present. ICGA allowed a more precise
      evaluation of lacquer cracks which appeared more numerous than the ones
      identified by FA. ICGA visualized the retrobulbar vasculature. This study shows
      that ICGA has a useful role for diagnosing and managing pathological myopia.

PMID- 8744850
TI  - Peripheral choroidal neovascularization.
AB  - Peripheral choroidal neovascularization can result in an elevated subretinal
      lesion which can simulate a choroidal tumor. We reviewed 8 eyes with 11
      peripheral areas of subretinal fluid and exudate which were subsequently
      determined to be secondary to peripheral choroidal neovascularization. Previous
      reports of peripheral choroidal neovascularization have emphasized the
      hemorrhagic nature of these lesions which can simulate a choroidal melanoma. In
      contrast, turbid subretinal fluid and exudate characterized the majority of
      peripheral lesions in this series and the majority of these patients were
      referred with a diagnosis of choroidal metastasis. Clinical examination with
      fluorescein angiography and echography can effectively distinguish these areas of
      peripheral choroidal neovascularization from choroidal metastasis.

PMID- 8744851
TI  - Vitreous changes and retinal detachment in highly myopic eyes.
AB  - This report on 496 highly myopic eyes that underwent transcleral or vitreoretinal
      surgery for retinal detachment (RD) focuses particularly on how changes in the
      vitreous gel and the resulting modifications of the vitreoretinal interface
      produce typical characteristics and complications. According to the pattern of
      vitreous modifications the 496 eyes were divided into five groups: 1) eyes with
      uniform PVD (108 eyes) 2) eyes with PVD spreading towards the upper quadrants
      (231 eyes) 3) eyes with extensive vitreous liquefaction (EVL) and condensations
      of the vitreous base (51 eyes) 4) eyes with posterior vitreous lacuna (PVL, 87
      eyes) 5) eyes with very limited PVD (19 eyes). Age, degree of myopia, surgical
      procedures and final results are reported for each group. A strong correlation
      was observed between vitreous changes and clinical picture of RD especially in
      the group of PVL and EVL. In the PVL group a higher degree of myopia was found
      and more pronounced posterior staphyloma. Frequently the posterior hyaloid, in
      the form of a thin, extremely smooth membrane, was hard to separate from the
      inner posterior retina during surgery. Posterior retinal breaks, including
      macular holes, were found in 56% of eyes. The presence of EVL with condensation
      of the vitreous base was correlated with giant retinal tear (GRT) in 70% of cases
      (36 of 51 eyes). Sixteen GRT were also found in the group of uniform PVD, but
      these were less extensive and located more posteriorly than in the EVL group. In
      the former group there were better surgical results because of a lower incidence
      of PVR. In 46% of the eyes of our series (group 2), PVD extended mostly in the
      upper quadrants with no vitreous detachment inferiorly. In these cases there was
      a clinical appearance of inferior vitreous collapse. These eyes had 92% of
      peripheral superior retinal breaks. Relapses of RD in this group almost
      invariably occurred in the inferior quadrants.

PMID- 8744852
TI  - Alteration of visual function in impaired glucose tolerance.
AB  - People with impaired glucose tolerance are considered to be prone to diabetes. To
      evaluate their visual function we investigated colour vision with the Farnsworth
      Munsell 100 Hue test and contrast sensitivity with Arden's grating cards in
      people with imparied glucose tolerance (IGT), people with normal glucose
      tolerance (NGT) and others with type II diabetes (NIDDM). Eyes with low vision or
      any anterior or posterior segment abnormalities were excluded. Contrast
      sensitivity and color vision differed significantly between the groups (p <
      0.01). It thus appears that patients with IGT but without clinical diabetes could
      be followed up to see whether these alterations have any predictive value for the
      development of diabetes and diabetic retinopathy.

PMID- 8744853
TI  - Homonymous bilateral hemianopsia: electrophysiological study of a case.
AB  - Described is a case of bilateral homonymous hemianopsia with macular sparing,
      resulting from head trauma. The case presented lesions of the occipital visual
      areas which involved entirely the left hemisphere and only partially the right
      hemisphere. VEP were obtainable only from electrodes placed on the right
      hemisphere with both right eye and left eye stimulation. VEP mapping showed that
      each eye projects macular fibres towards functional areas of the right occipital
      hemisphere. Electrophysiological examination confirmed objectively and for the
      first time in man the theory of "double cortical macular representation".
      Clinical implications of this finding are discussed.

PMID- 8744854
TI  - Ophthalmologic aspects of pituitary apoplexy.
AB  - Pituitary apoplexy is an acute hemorragic or ischemic infarction in pituitary
      adenomas. The incidence in our series was 6.5%. Clinical diagnosis can often be
      difficult as the patient is frequently unaware of an existing adenoma (seven out
      of 11 patients). Therefore, the classic features of the syndrome must be known.
      They include sudden headaches, impairment of consciousness, endocrinological
      disturbances and sudden visual deterioration or oculomotor palsies. In this
      retrospective study from 1987 to 1994 of 14 patients presenting pituitary
      apoplexy there were 11 cases with visual abnormalities. Oculomotor palsies were
      more common (82%) than chiasmatic impairment (54.5%) and often revealed pituitary
      adenoma. CT-Scan and MRI examinations led to diagnosis, and emergency treatment
      (surgical removal by rhinoseptal approach or less often medical treatment)
      generally led to a regression of visual disturbances.

PMID- 8744855
TI  - Temporary silicone oil tamponade and intraocular pressure: an 11-year
      retrospective study.
AB  - BACKGROUND: A retrospective study was conducted to evaluate the risk of increased
      intraocular pressure (IOP) following a temporary silicone oil (SO) tamponade and
      to study some parameters possibly involved in this hypertension. METHODS: Forty
      four patients with retinal detachment complicated by proliferative
      vitreoretinopathy (PVR) were treated by vitreoretinal surgery and SO tamponade.
      One to 11 years after SO removal, they underwent full ophthalmic examination. All
      these patients had a healthy, non-operated, normotensive fellow eye. RESULTS: Six
      (14%) of 44 eyes had IOP higher than 20 mmHg. Five other eyes (11%) had their IOP
      controlled by beta blockers. Phakic and pseudophakic eyes had a very limited
      tendency to develop ocular hypertension and anyway responded well to beta
      blockers. Residual SO droplets in the eye after removal of the big bubble of SO
      disappeared exponentially with a mean disappearance time of three years. Eyes
      with residual SO were no more prone to ocular hypertension than those without (p
      > 0.50). No association was found between IOP and duration of SO tamponade (r =
      0.13) or between IOP and flare (r = 0.14). CONCLUSION: This study suggests that
      the risk of developing ocular hypertension after a temporary SO tamponade is
      moderate. No satisfactory explanation could be found for this increase of IOP.

PMID- 8744856
TI  - Visual function during acute hypoglycaemia.
AB  - Hypoglycaemia symptoms are of particular interest in view of the importance of
      hypoglycaemia unawareness. Visual symptoms arising during acute hypoglycaemia may
      be the result of metabolic disturbances in the visual pathways within the central
      nervous system or impairment of the refractive apparatus of the eye and binocular
      function. This study investigated the effect of hypoglycaemia upon visual acuity,
      binocular interaction and contrast sensitivity. Various aspects of visual
      function were examined in ten normal subjects before, during and after acute
      insulin-induced hypoglycaemia. A simultaneous study of hypoglycaemic symptoms
      enabled us to relate the objective findings to the symptoms as reported by the
      subjects. Snellen visual acuity, fusion and stereopsis were not affected by
      hypoglycaemia. Five subjects noted visual disturbance. Eight developed
      significant impairment of contrast sensitivity, which closely matched the lowered
      blood glucose concentration. These observations suggest that hypoglycaemic visual
      symptoms are due to neuroglycopenia of central visual pathways rather than
      changes within the refractive apparatus or abnormality of binocular function.
      Although these symptoms are not a constant feature of the hypoglycaemic state,
      subtle impairment of visual function occurs in most cases. Contrast sensitivity
      testing can be useful for assessment of fine changes in visual function.

PMID- 8744857
TI  - Simultaneous bilateral primary choroidal melanoma.
AB  - A case of bilateral primary choroidal melanoma is described. To our knowledge,
      this is the first reported case in Spain. On admission of a 70-year-old man for a
      choroidal melanoma in the right eye, an asymptomatic tumor was detected in the
      periphery of his left eye. A-scan ultrasonography, fluorescein angiography and
      diascleral transillumination supported the diagnosis of choroidal melanoma in
      both eyes. The right eye was enucleated. Histology confirmed a choroidal melanoma
      of the mixed type. The left eye was treated with laser photo-coagulation and an
      episcleral plaque of ruthenium-106. Careful systemic evaluation produced no
      evidence of a primary tumor or metastatic disease elsewhere in the body. Because
      of the impossibility, in most cases, of obtaining histological confirmation in
      both eyes, and the tendency of choroidal melanomas to metastatize late, we
      suggest that the criteria of independent origin (two separate cell types and
      tumors separated in time) are not necessary in cases of presumed bilateral
      choroidal melanoma.

PMID- 8744858
TI  - Transvaginal sonographic diagnosis of cataract in a fetus.
AB  - Transvaginal ultrasonography is a relatively new technique for visualizing the
      orbits in a fetus of 4 to 5 cm. At fifteen weeks of gestation it is possible to
      recognize the lenses and the hyaloid arteries in the eyes, to diagnose structural
      malformations such as anophthalmos, microphthalmos, buphthalmos and moderate to
      severe cataract. In most cases cataracts were associated with intracranial
      defects. We describe a case where the sonographic diagnosis of fetal cataract was
      confirmed by histopathological examination. A 27-year-old woman had a routine
      transvaginal sonography at 15 weeks' normal gestation. Microphthalmos without a
      hyaloid artery and disorganization of the anterior chamber and lens consistent
      with cataract were demonstrated in the fetal left eye. In accordance with the
      parents' decision, the pregnancy was terminated a week later. Autopsy of the
      fetus was done and serial sections of the left eye were studied by light
      microscopy. Histopathological examination verified the sonographic diagnosis of
      fetal cataract in a microphthalmic eye. Associated findings included malformation
      of the anterior segment and retinal dysplasia.

PMID- 8744859
TI  - Serum uric acid levels in diabetic patients with and without retinopathy.

PMID- 8744860
TI  - Vision for the world.

PMID- 8744861
TI  - The lumbar and femoral bone mineral densities in a normal female Puerto Rican
      population.
AB  - The aim of this study was to establish the reference values of the bone mineral
      density (BMD) of the lumbar spine and the proximal femur in a normal adult female
      Puerto Rican population. In the selection of the population, exclusion criteria
      included diseases, use of drugs and toxic habits (smoking and alcoholism) known
      to affect bone and mineral metabolism. The study population comprised 131 healthy
      females, ages 20 to 69 years. Spinal radiographs were taken of women age 60 or
      more to exclude spinal defects or artifacts. The bone mineral densities were
      measured using the dual energy X Ray absorptiometer (DEXA, Hologic model 1000).
      The peak BMD was found in the lumbar spine at the age 30 to 39 years and at the
      age 20 to 29 years in the femoral neck, trochanter and Ward's triangle. The
      decrease in BMD from peak values to those at age 60 to 69 years were 18% for the
      lumbar spine, 16.3% for the femoral neck, 30.1% for the Ward's triangle and 12.4%
      for the trochanter. The major fall in the BMD was related to the menopause and
      compares with that of other series. There was no statistical difference from
      Hologic reference values in a mixed population of the USA.

PMID- 8744862
TI  - Slow cluster formation of purified human or rhesus T cells requires protein
      kinase C and LFA-1.
AB  - Homotropic T cell adhesion, as generally studied, consists of a rapid, transient
      binding process that is measured over a 15-120 min. period. Here we report a slow
      type of adhesion process occurring with human or rhesus T cells, purified from
      peripheral blood, that manifests itself by the formation of rounded, multi-layer
      clusters which may contain hundreds of cells. The maximal number and size of the
      clusters peak 1-2 days after the addition of phorbol ester, an absolute
      requirement. The number of clusters formed is proportional to phorbol ester
      concentration up to 1.25 ng/mL. Phorbol esters such as phorbol myristate acetate
      (PMA), phorbol dibutyrate (PDB), and 7-octylindolactam (OIL) induced optimal
      cluster formation at 1-13 ng/mL, levels slightly higher than that required to
      induce mitogenesis of purified T cells. Phorbol itself and the alpha-form of the
      ester were inactive. Both cluster formation and mitogenesis (stimulated by Con A
      or anti-CD3) are completely inhibited by staurosporin at 12.5 ng/mL. Even at 2.5
      ng/mL, 74% of cluster formation was inhibited, which strongly implies a crucial
      role for protein kinase C. In the presence of accessory cells, T cell clusters
      were suppressed. Monoclonal Ab such as anti-CD3, mouse anti-CD3 followed by anti
      mouse IgG, anti-CD4, anti-CD4A, anti-CD2, anti-CD8, and anti-CD45 did not induce
      cluster formation. None were inhibitory or stimulatory in the presence of PMA,
      except for anti-CD3 which enhanced cluster formation by 26%. However, anti-LFA-1
      beta-chain (mouse monoclonal) completely blocked cluster formation over the range
      studied (63-1000 ng/mL) for both human and rhesus cells; rat anti-LFA-1 only
      blocked human cell adhesion. Anti LFA-1 only partially inhibited T cell
      mitogenesis. These results show that slow cluster formation shares the LFA-1 and
      phorbol ester requirements of the rapid adhesion of T cells requiring LFA-1 and
      ICAM-1. However, cluster occurs at a very low phorbol ester concentration,
      appears more sensitive to staurosporin inhibition, and is not stimulated via the
      TCR receptor like the rapid adhesion process. We hypothesize that certain
      neuronal processes, induced by phorbol ester, and which also show a similar
      protein kinase C activation time course, may share mechanisms in common with
      cluster formation.

PMID- 8744863
TI  - Sustained levels of ascorbic acid are toxic and immunosuppressive for human T
      cells.
AB  - Ascorbate (vitamin C) can protect from oxidative damage to DNA and lipids that
      may lead to aging, cancer, and other dysfunctions. However, we find that purified
      human T cells deteriorate if maintained in ascorbate in culture for 18 hrs. or
      more; viability and Il-2 synthesis are over 90% curtailed by ascorbate at 50
      micrograms/ml. T cell proliferation and adhesion are severely suppressed at 10-25
      micrograms/ml. Dihydro-ascorbate was much less toxic or suppressive. The
      suppressive effect of ascorbate appears irreversible, since removal of ascorbate
      after 18 hrs. did not restore the mitogenic response. Although moderate dietary
      levels of ascorbate often reach 250-1000 mg or more daily and appear beneficial,
      our data caution against sustained megadoses of ascorbate for treatment of
      patients with AIDS and cancer.

PMID- 8744864
TI  - Prevalence of tuberculin reactivity and prevalence of risk factors for the
      development of active tuberculosis in a nursing home in Puerto Rico.
AB  - A total of 91 nursing home patients were evaluated to determine the prevalence of
      tuberculous infection and the prevalence of risk factors for active TB in those
      with positive tuberculin reactions. Overall prevalence rate for positive PPD was
      42.9%. No association was found between prevalence of positive PPD and time since
      admission to the nursing home. The most prevalent risk factors for active TB
      among PPD positive patients were diabetes mellitus (38.5%), being 10% below ideal
      body weight (25.6%), chest X ray with fibrotic changes (13.2%), and carcinoma of
      oropharynx (5.1%). Twenty-one patients (53.8% of patients with positive test) met
      criteria for prophylactic treatment with isoniazid. This study detected a high
      prevalence of positive PPD reactions in this nursing home population and a high
      prevalence of risk factors for the development of active TB in the group with
      positive reaction to PPD. Due to the high risk for the development of active
      tuberculosis in this population, aggressive screening and preventive therapy are
      mandatory.

PMID- 8744865
TI  - Hay Bilharzia!, by Klock, Ildefonso, and Mateo-Serrano: medical images of poverty
      and development in Puerto Rico in the 1950s.
AB  - From 1940 to 1970 Puerto Rico underwent a dramatic change in its economic,
      social, political, and medical characteristics. Schistosomiasis (known locally as
      bilharzia) persisted throughout this period as a nearly intractable problem. In
      1954, staff from the Puerto Rico Department of Health, and the Puerto Rico Field
      Station of the U.S. Communicable Disease Center (now San Juan Laboratories,
      Centers for Disease Control and Prevention) created a set of black and white 35
      mm slides as a tool for community education. The presentation, titled "Hay
      Bilharzia!" ("There is schistosomiasis here!") is organized in four major
      sections (Introduction, Disease Cycle, Disease Prevention, Treatment). Each
      section consists of two to four sub-themes, with three to eight slides each. The
      slides were used extensively in public schools and community lectures. This set
      of slides is worthy of preservation as evidence of the bilharzia control efforts
      and the dismal living conditions widely prevalent in Puerto Rico in the 1950s. It
      is also an example of the educational programs that were produced at the time to
      stimulate community development and health.

PMID- 8744866
TI  - 1995 Bailey K. Ashford lecture. Public health lessons from two catastrophic
      epidemics: the toxic oil syndrome and the eosinophilia-myalgia syndrome.

PMID- 8744867
TI  - Syncope produced by metastatic carcinoma of the tongue to the carotid body.

PMID- 8744868
TI  - Worksite health programs: working together to advance employee health.

PMID- 8744869
TI  - The ecology of work and health: research and policy directions for the promotion
      of employee health.
AB  - This article identifies new research and policy directions for the field of
      worksite health in the context of the changing American workplace. These
      directions are viewed from an ecological perspective on worksite health and are
      organized around three major themes: (1) the joint influence of physical and
      social environmental factors on occupational health, (2) the effects of
      nonoccupational settings (e.g., households, the health care system) on employee
      well-being and the implications of recent changes in these settings for worksite
      health programs, and (3) methodological issues in the design and evaluation of
      worksite health programs. Developments in these areas suggest that the field of
      worksite health may be undergoing a fundamental paradigm shift away from
      individually oriented wellness programs (provided at the worksite and aimed
      primarily at changing employees' health behavior) and toward broader formulations
      emphasizing the joint impact of the physical and social environment at work, job
      person fit, and work policies on employee well-being.

PMID- 8744870
TI  - A work-systems analysis of compliance with universal precautions among health
      care workers.
AB  - Universal precautions are work practices designed to protect health care workers
      from occupational exposure to HIV and other bloodborne pathogens. However,
      despite aggressive dissemination efforts by CDC and regulatory action by OSHA,
      compliance remains less than satisfactory. This article argues that the
      minimization of risk from bloodborne pathogens requires a multilevel or work
      systems perspective that considers individual, job/task, and
      environmental/organizational factors. The available literature on universal
      precautions suggests the potential of such an approach and provides insight into
      the limited success of current worker-focused mitigation efforts. In particular,
      specific opportunities exist to develop and apply engineering controls, to
      improve the design and organization of jobs and tasks, and to create
      organizations that facilitate and reinforce safe behavior.

PMID- 8744871
TI  - The integrated model: implications for worksite health promotion and occupational
      health and safety practice.
AB  - Within a single firm it is common to find both occupational safety and health and
      worksite health promotion interventions operating in isolation from one another,
      with different intervention targets, methods, and personnel. Overcoming the
      segmentation of the two fields will require, among other things, the promulgation
      of an overarching model of work and health. The purpose of this article is to
      describe an integrated model and to show how it can be applied to improve
      worksite health interventions for both occupational safety and health and
      worksite health promotion. Practice examples from both fields are used to
      illustrate interventions that focus on different areas of the model (individual
      behavior, psychosocial, organization, and contextual factors). It is argued that
      occupational safety and health and worksite health promotion practitioners need
      to develop more comprehensive interventions and rigorously evaluate these
      programs to determine if they are more effective than programs with a more narrow
      focus.

PMID- 8744872
TI  - Worker participation in an integrated health promotion/health protection program:
      results from the WellWorks project.
AB  - According to prior reports, blue-collar workers are less likely to participate in
      worksite health promotion programs than are white-collar workers. This study
      examined worker participation in the WellWorks worksite cancer prevention
      intervention, which integrated health promotion and health protection. Analyses
      were conducted to assess relationships among participation in health promotion
      and health protection programs, and workers' perceptions of management changes to
      reduce potential occupational exposures. Results indicate that blue-collar
      workers were less likely to report participating in health promotion activities
      than white-collar workers. A significant association was observed between
      participation in nutrition- and exposure-related activities, suggesting that
      participation in programs to reduce exposures to occupational hazards might
      contribute to blue-collar workers' participation in health promotion activities.
      Furthermore, when workers were aware of changes their employer had made to reduce
      exposures to occupational hazards, they were more likely to participate in both
      smoking control and nutrition activities, even when controlling for job category.
      These findings have clear implications for future worksite cancer prevention
      efforts.

PMID- 8744873
TI  - Effect of organization-level variables on differential employee participation in
      10 federal worksite health promotion programs.
AB  - Guided by a conceptual model, the authors used both qualitative data (e.g.,
      individual interviews, focus groups) and quantitative data from an employee
      survey (N = 3,388) in 10 federal agencies to investigate whether organization
      context and implementation process affected participation in worksite health
      promotion and disease prevention (HPDP) activities among demographic subgroups.
      Overall, employees on average participated in fewer than two agency-supported
      health-related activities per year (17% in fitness, 40% in health risk assessment
      activities). Employees participated more where coworkers endorsed such programs.
      Minority employees and employees in lower level positions were more likely to
      participate in fitness activities when organizations had a more comprehensive
      program structure, engaged in more marketing strategies, gave time off to
      employees to participate, or had on-site facilities. Management support for the
      program was related to participation by employees who were male, white, and had
      upper level positions. The data supported the proposed model; also confirmed was
      two predicted relationships between model constructs, which provided a better
      understanding of differential participation by employee groups.

PMID- 8744874
TI  - Linking stress and injury in the farming environment: a secondary analysis of
      qualitative data.
AB  - The first step in injury prevention is to understand the injury problem. This
      includes examining the nature of the problem from the perspective of the target
      community. This article uses qualitative methods to explain the nature of the
      injury problem and identifies prevention strategies through a three-step process:
      identify a causal model, validate the model, and identify strategies using the
      causal model. A causal model linking safety performance and safety demand, health
      decision making, and occupational stress was derived by secondary analysis of
      farm family focus group data (step 1) and validated by other farm family focus
      groups (step 2). Prevention strategies identified from the causal model (step 3)
      include decreasing the number of roles performed exclusively by one individual,
      developing an easy-to-use planning tool that assists farmers in anticipating and
      reducing future work demands, and developing an education module that
      incorporates injury costs into safety decision making.

PMID- 8744875
TI  - Operationalizing theoretical constructs in bloodborne pathogens training
      curriculum.
AB  - This article describes how the protection motivation theory (PMT) was used to
      inform the production of video curriculum for a bloodborne pathogens training
      program for hospital nurses. Although hospital nurses are well acquainted with
      the work practices designed to prevent bloodborne pathogen exposures (universal
      precautions), there is evidence that they do not always follow them. First, the
      original PMT is adapted to reflect what is currently known about the role of
      affect in health behavior prediction. Second, the authors show how the four PMT
      message constructs-probability of occurrence, magnitude of noxiousness, response
      efficacy, and self-efficacy-guided the planning, shooting, and editing of the
      videotapes. Incidental to this process was the operationalization of these
      message constructs in such a way that affective reactions would result. The
      results show that this video curriculum successfully aroused negative affect in
      the target audience. Only by carefully planning and documenting how message
      constructs are operationalized in health education materials can one be sure of
      achieving theory-based (and thus the most replicable) message design.

PMID- 8744877
TI  - Evaluation of internists' spirometric interpretations.
AB  - BACKGROUND: Correct interpretation of screening spirometry results is essential
      in making accurate clinical diagnoses and directing subsequent pulmonary
      evaluation. The general internist is largely responsible for interpreting
      screening spirometric tests at community hospitals. However, reports of new
      guidelines for screening spirometry are infrequently published in the general
      internal medicine literature. This can lead to incorrect interpretations. We
      sought to evaluate whether spirometric interpretations by a group of practicing
      general internists differed from those of two board-certified pulmonologists
      using guidelines published by the American Thoracic Society (ATS). METHODS: As
      part of a Continuous Quality Improvement project, all available screening
      spirometric tests over a 3-month period at two area community hospitals were
      reviewed. Only those performed on individuals age 18 or older were included in
      the analysis. Comparison was made between the interpretations of staff internists
      and those of two pulmonologists, who were blinded to the results of all other
      interpretations. We analyzed 110 screening spirometric tests from 84 males and 26
      females. The patients ranged in age from 18 to 77 (mean 41 +/- 13 years of age).
      RESULTS: There was 97% concordance between the two pulmonologists'
      interpretations. In three cases, interpretations of only one pulmonologist agreed
      with those of the internists. The internists and both pulmonologists agreed in 73
      cases. The majority of spirometric results in this subgroup were normal (n = 54).
      Both pulmonologists disagreed with internists' nomenclature in five cases. There
      was complete disagreement between the pulmonologists and the internists in the
      other 29 cases. Using the pulmonologists' interpretations as the "gold standard,"
      the sensitivity (the internists' ability to correctly identify abnormal
      spirometric results) was 58.8% (95% confidence interval [CI] 42.2%, 73.3%), the
      specificity was 81.8% (95% CI 70.0%, 89.8%), the positive predictive value was
      66.7% (95% CI 49.0%, 80.9%), and the negative predictive value was 76.1% (95% CI
      64.3%, 85.0%). The most common inaccurate interpretations made by internists were
      "small airways disease" when spirometric results were normal (n = 8); "normal"
      when a restrictive pattern was present (n = 6), and "normal" when an abnormal
      flow-volume loop suggesting possible upper airway obstruction was present (n =
      5). CONCLUSIONS: The spirometric interpretations of a group of general internists
      differed significantly from those of two board-certified pulmonologists using
      published guidelines in approximately one third of cases. This may be because
      subspecialty guidelines are infrequently published in the general internal
      medicine literature. We believe that wider dissemination of these interpretative
      guidelines and ongoing physician education would improve general internists'
      ability to identify patients who require further pulmonary evaluation.

PMID- 8744876
TI  - Effect of physician gender on the prescription of estrogen replacement therapy.
AB  - OBJECTIVE: To determine if women cared for by female physicians are more likely
      to receive postmenopausal estrogen replacement therapy than women cared for by
      male physicians. DESIGN: Case-control study with follow-up telephone survey.
      SETTING: An outpatient practice at an urban teaching hospital in Boston,
      Massachusetts. PARTICIPANTS: Subjects were women begun on estrogen replacement
      therapy during an 18-month period; controls were matched on age and month of
      visit. Seventy-one cases (mean age 60 years, 41% nonwhite) and 142 controls (mean
      age 60 years, 48% nonwhite) were identified. Fifty-two (82%) of 64 eligible case
      patients and 89 (80%) of 111 eligible control patients completed a follow-up
      telephone interview assessing their preferences for female physicians and
      interest in estrogen replacement therapy. MAIN RESULTS: After adjusting for
      potential confounders using conditional logistic regression, patients with female
      physicians were more likely to begin estrogen replacement therapy than those seen
      by male physicians (odds ratio [OR] 5.4; 95% confidence interval [CI] 1.8, 15.3).
      Case patients selected their primary care physician more often than control
      patients and were more interested in estrogen replacement therapy. After
      adjusting for potential confounders including patients' preferences to select
      their physician and their interest in estrogen replacement therapy, patients with
      female physicians were still more likely to begin estrogen replacement therapy
      than those seen by male physicians (OR 11.4, 95% CI 1.1, 113.6). CONCLUSIONS: We
      conclude that female patients are more likely to be prescribed estrogen
      replacement therapy if they are cared for by female physicians rather than male
      physicians even after accounting for patient preferences. Further research is
      required to determine whether these differences reflect differences in
      physicians' knowledge or attitudes regarding estrogen replacement therapy or
      reflect gender differences in how physicians discuss estrogen replacement therapy
      with their patients.

PMID- 8744878
TI  - Gender differences in the management of acute chest pain. Support for the "Yentl
      syndrome".
AB  - OBJECTIVE: To determine whether evaluation and management of males and females
      differ after presentation to the emergency department with acute chest pain.
      DESIGN: Prospective cohort study with follow-up at 1 month. SETTING: Urban
      teaching hospital. PATIENTS: The study population included 1,411 patients who
      were 30 years of age or older who visited the emergency department with acute
      chest pain from October 1990 through May 1992. These 1,411 patients represent 69%
      of the 2,056 patients approached for consent. The utilization of exercise stress
      testing as outpatients was measured for a subset of 954 patients who were
      interviewed at 1 month after their presentation. MEASUREMENTS/MAIN RESULTS: After
      controlling for clinical and nonclinical predictors, women were less likely to be
      admitted to the hospital (adjusted odds ratio [OR] 0.68; 95% confidence interval
      [CI] 0.47, 0.99). Among the 954 patients with 1-month follow-up, women were less
      likely than men to undergo an exercise stress test during the first month after
      presentation, with borderline statistical significance after adjusting for the
      interaction between gender and admission to the hospital (adjusted OR 0.30; 95%
      CI 0.09, 1.0). Among the patients who were admitted to the hospital, women were
      as likely as men to undergo exercise stress testing (adjusted OR 0.81; 95% CI
      0.57, 1.2) but were less likely to undergo cardiac catheterization (adjusted OR
      0.44; 95% CI 0.25, 0.80). CONCLUSIONS: Gender-based differences in management may
      occur at several stages in the evaluation of patients with acute chest pain.
      Observed differences in use of invasive procedures between men and women may be
      due in part to lower rates of exercise test use and admission to the hospital for
      evaluation of acute chest pain.

PMID- 8744879
TI  - Primary care physicians' medical decision making for late-life depression.
AB  - OBJECTIVE: To describe primary care physicians' clinical decision making
      regarding late-life depression. DESIGN: Longitudinal collection of data regarding
      physicians' clinical assessments and the volume and content of patients'
      ambulatory visits as part of a randomized clinical trial of a physician-targeted
      intervention to improve the treatment of late-life depression. SETTING: Academic
      primary care group practice. PATIENTS/PARTICIPANTS: One-hundred and eleven
      primary care physicians who completed a structured questionnaire to describe
      their clinical assessments immediately following their evaluations of 222 elderly
      patients who had reported symptoms of depression on screening questionnaires.
      INTERVENTIONS: Intervention physicians were provided with their patient's score
      on the Hamilton Depression rating scale (HAM-D) and patient-specific treatment
      recommendations prior to completing the questionnaire regarding their clinical
      assessment. MAIN RESULTS: Those physicians not provided HAM-D scores were just as
      likely to rate their patients as depressed, as determined by specific query of
      these physicians regarding their clinical assessments. A physician's clinical
      rating of likely depression did not consistently result in the formulation of
      treatment intentions or actions. Treatment intentions and actions were
      facilitated by provision of treatment algorithms, but treatment was received by
      fewer than half of the patients whom physicians intended to treat. Barriers to
      treatment appear to include both physician and patient doubts about treatment
      benefits. CONCLUSIONS: Lack of recognition of depressive symptoms did not appear
      to be the primary barrier to treatment. Recognition of symptoms and access to
      treatment algorithms did not consistently result in progression to subsequent
      stages in treatment decision making. More research is needed to determine how
      patients and physicians weigh the potential risks and benefits of treatment and
      how accurately they make these judgments.

PMID- 8744880
TI  - A case of hypertension.

PMID- 8744882
TI  - Predicting daily visits to a walk-in clinic and emergency department using
      calendar and weather data.
AB  - We studied the association between calendar and weather variables and daily
      unscheduled patient volume in a walk-in clinic and emergency department. Calendar
      variables (season, week of month, day of week, holidays, and federal check
      delivery days) and weather variables (high temperature and snowfall) forecasted
      clinic volume, explaining 84% of daily variance and 44% of weekday variance.
      Staffing according to predicted volume could have decreased overstaffing from 59%
      to 15% of days, but would have increased understaffing from 2% to 18% of days.
      Models using calendar and weather data that forecast local utilization may help
      to schedule staffing for walk-in clinics and emergency departments more
      efficiently.

PMID- 8744881
TI  - The common cold.

PMID- 8744883
TI  - Antihistamines and the common cold. A review and critique of the literature.
AB  - OBJECTIVE: To determine if antihistamines provided clinically significant relief
      from the symptoms of the common cold. METHODS: Structured literature review
      following standardized guidelines of primary studies published after 1975.
      MEASUREMENTS: Improvements in symptom scores for total symptoms and nasal
      symptoms over the first three days of a common cold. RESULTS: Three of five
      studies reporting on sneezing found a statistically significant improvement in
      the antihistamine group; similarly, three of seven studies reporting on nasal
      discharge found a statistically significant improvement with therapy. No study
      reported improvement in total symptom score at the level of p < .05. The validity
      of these findings was weakened by several flaws in the literature such as
      inattention to clinical significance and functional impact, inappropriate use of
      statistical tests, and poorly described methodology. The clinical significance of
      these improvements was not demonstrated. CONCLUSIONS: The primary literature
      offers little support for the use of antihistamines in the common cold.

PMID- 8744884
TI  - Dividing up the turf. Generalists versus specialists.

PMID- 8744885
TI  - When does a generalist need a specialist?

PMID- 8744886
TI  - Using the biopsychosocial model in practice. Improving the care of patients with
      late-life depression.

PMID- 8744887
TI  - Announcing "from research to practice".

PMID- 8744888
TI  - Physician malpractice: does the past predict the future?

PMID- 8744889
TI  - Cost of hypertension treatment.

PMID- 8744890
TI  - Hysterectomy charges: geographic variations United States, 1994.
AB  - During 1994 Metropolitan Life Insurance Company claims by group health insureds
      and their dependents for a vaginal hysterectomy averaged $10,500, for an
      abdominal hysterectomy (laparotomy), $12,440, and for a laparoscopically assisted
      vaginal hysterectomy (LAVH), $13,840. The distributions of the three surgeries
      varied by geographic area and state. The East South Central states had the lowest
      average total charge for each procedure whereas the highest charge for a
      laparotomy was reported in the Middle Atlantic states; the highest vaginal
      hysterectomy charge was in the Pacific area, and LAVH average total charge was
      the highest in New England. Of the three surgeries, the vaginal hysterectomy
      charges varied the most by state-the average charge in Florida was almost twice
      that in Oklahoma. Laparotomy charges differed by 59 percent between California
      and Tennessee, where they were 30 percent above and 19 percent below the U.S.
      norm, respectively. The total charge for the LAVHs varied by 42 percent and was
      the highest in California and lowest in North Carolina. Three study states,
      California, Florida and Illinois, were among the four states with the highest
      average total charges for each form of hysterectomy. Physicians' fees accounted
      for 41 percent of vaginal hysterectomy charges, 37 percent of the laparotomy
      total charges, and 34 percent of the LAVH charges. Of the laparotomies, the
      physicians' fees differed by 132 percent between the highest in New York and the
      lowest in Tennessee. For the country as a whole, the average length of stay was
      2.17 days for the LAVHs, 2.54 days for a vaginal hysterectomy and 3.43 days for
      an abdominal hysterectomy.

PMID- 8744891
TI  - Choosing a standard for adjusted mortality rates.
AB  - For over half a century, the standard for age-adjustment in mortality studies has
      been based on the total population according to the 1940 census. The question
      periodically arises, however, whether a more recent census population might now
      be more appropriate. Thus, a study using the six censuses from 1940 to 1990 was
      conducted to see the effect each of these populations would have on the age
      adjusted (standardized) death rates. While the size of the age-adjusted rates was
      affected by the censal standard populations from 1940 to 1990, these populations
      hardly changed the proportional mortality by age, sex, cause-of-death and
      geographic area. It appears that a shift from the 1940 standard will not be
      necessary, although if more detailed comparisons are needed, age-specific death
      rates can always be used. The 1940 standard also has the advantage of being
      consistent with many earlier studies.

PMID- 8744892
TI  - Household savings in the United States: trends and outlook.
AB  - During the post-World War II period, the United States has had a low rate of
      household saving compared with other developed countries. The latest saving rate
      remains close to an historically low level, slightly over 4 percent of personal
      disposable income. This rate is about half that recorded between 1980 and 1985.
      Various possible reasons for the decline of the U.S. saving rate are discussed
      and include lack of growth in real income; the life-cycle movement of the baby
      boomers; and the "wealth effect" from rising asset values. As the baby boom
      generation matures, the household saving rate should increase. By the year 2000
      households headed by persons aged 45-54 will rise to 20 percent and then to 22
      percent by 2010. An increase in the number of such households should boost both
      aggregate and rate of U.S. saving. Independent saving is encouraged to help
      lessen the impact that changes in Social Security and continued corporate
      restructuring might have in the future.

PMID- 8744893
TI  - State variation in rates of cesarean and VBAC delivery: 1989 and 1993.
AB  - There is wide variation among states in rates of cesarean and vaginal births
      after cesarean (VBAC) deliveries. In general, states in the South have the
      highest cesarean rates, states in the West have the lowest, and states in the
      Northeast and Midwest are intermediate. Louisiana had the highest overall rate in
      1993 (27.7 per 100 births) while Alaska had the lowest rate (15.2). The majority
      of states had declines in their cesarean rate between 1989 and 1993. Patterns in
      primary cesarean rates are similar to those of the overall rate-states in the
      South generally have the highest rates while states in the West have the lowest
      rates. Primary cesarean rates ranged between a high of 19.6 in Louisiana to a low
      of 10.6 in Wisconsin. In general, states with low cesarean rates have among the
      highest rates of VBAC delivery. Alaska had the highest VBAC rate (40.0), which
      was almost quadruple the rate of Louisiana (11.2), the state with the lowest
      rate. Most states had substantial increases in VBAC rates between 1989 and 1993.
      When examining cesarean rates by maternal age and birth order, states with the
      highest overall rates also have among the highest age/birth order-specific rates.
      Cesarean rates were lowest for mothers under 25 years of age having a second or
      higher order birth in Alaska, 10.4, and highest for mothers 35 years of age or
      over having a first birth in Mississippi, 51.3. Standardized cesarean rates which
      were adjusted for differences between states in maternal age and birth order
      distributions did not diminish the variation among areas.

PMID- 8744894
TI  - The interaction of Fe(III), adriamycin and daunomycin with nucleotides and DNA
      and their effects on cell growth of fibroblasts (NIH-3T3).
AB  - The interactions of the iron complexes of the anthracycline antitumour drugs
      daunomycin (DN) and adriamycin (ADM) with the mononucleotide AMP, herring sperm
      DNA, plasmic pBR322 and immortalized 3T3 fibroblasts were studied. By means of
      Mossbauer spectroscopy it was demonstrated that DNA is a powerful ferric iron
      chelator as compared with AMP, which is not able to compete with DN or
      acetohydroxamic acid for ferric iron. The difference between AMP and DNA is
      postulated to be based on the chelate effect. The Mossbauer spectra of the
      ternary Fe-anthracycline-DNA systems differ from Fe-anthracycline binary
      complexes, indicating rearrangement reactions. Dialysis experiments clearly
      disclose the formation of a ternary Fe-ADM-pBR322 complex, the topology of which
      differs substantially from intercalating ADM. The effect of Fe-ADM complexes
      (3:1) on the growth of immortalized mouse embryonal fibroblasts (NIH-3T3) was
      studied in comparison with ADM alone. No significant difference on the inhibition
      of cell growth was noticed, suggesting comparable cytotoxicity for the compounds.
      In contrast to literature data, no evidence was found for DNA cleavage by ferric
      ADM at molar ratios as high as 1/100 (ADM/base pair), even if the ternary systems
      were prepared in the light and in the presence of reducing or oxidizing agents.
      Based on our observations it seems that the cytotoxicity of both ADM and Fe-ADM
      oligomer is not based primarily on intercalation or direct interaction with DNA.

PMID- 8744895
TI  - Production of superoxide dismutases from Proteus mirabilis and Proteus vulgaris.
AB  - Proteus mirabilis and Proteus vulgaris expressed a combination of superoxide
      dismutase (Sod) activities, which was assigned to FeSod1, FeSod2 and MnSod for P.
      mirabilis, and FeSod, MnSod and CuZnSod for P. vulgaris. Production of the Sod
      proteins was dependent on the availability of iron, whether cells were grown
      under anaerobiosis or aerobiosis and growth phase. Nalidixic acid and
      chloramphenicol inhibited cell growth and the iron- and dioxygen-dependent
      production of Sod. These results support the involvement of metal ions and redox
      status in the production of Proteus Sods.

PMID- 8744896
TI  - Evidence for the involvement of nitric oxide in cisplatin-induced toxicity in
      rats.
AB  - Cisplatin treatment of rats results into a significant increase in the activity
      of Ca(2+)-independent nitric oxide synthase (NOS) in kidneys and liver.
      Significant enhancement of lipid peroxidation in gastric mucosa, kidneys and
      liver was also observed. The administration of NG-nitro-L-arginine methyl ester,
      an inhibitor of NOS, markedly reduced renal and gastrointestinal toxicity, and
      also decreased the content of blood urea nitrogen, serum creatinine, and
      incidence of diarrhoea along with a significant inhibition in lipid peroxidation
      in the target organs. The present report, while demonstrating the beneficial
      effect of the blockade of NO pathways during cisplatin chemotherapy, may be
      helpful in developing strategies for combating some of the toxic side-effects of
      the drug.

PMID- 8744897
TI  - Desferrioxamine-dependent iron transport in Erwinia amylovora CFBP1430: cloning
      of the gene encoding the ferrioxamine receptor FoxR.
AB  - Iron deprivation of Erwinia amylovora CFBP1430, a species causing fire blight on
      Pomoideae, was shown to induce the production of siderophores of the
      desferrioxamine (dfo) family and two outer membrane polypeptides with apparent
      molecular weight of about 70 and 80 kDa, respectively. Cyclic dfo E was
      characterized as the major metabolite. Phage MudIIpR13 insertional mutagenesis
      and screening on CAS-agar medium yielded three dfo non-producing and one
      overproducing clones. These clones failed to grow in the presence of the Fe(III)
      chelator EDDHA and were determined further as dfo and ferrioxamine transport
      negative mutants, respectively. The transport mutant which appeared to lack the
      70 kDa polypeptide in the outer membrane allowed the purification of dfo E.
      Growth under iron limitation of dfo negative mutants was stimulated with
      ferrioxamine E and B but not with other ferrisiderophores tested. The host DNA
      sequence flanking the left terminal part of the MudIIpR13 prophage responsible
      for the transport mutation was cloned and used to probe a parental gene library
      by DNA-DNA hybridization. Two recombinant cosmids restoring the transport
      mutation to normal were identified. Both cosmids also conferred the ability to
      utilize ferrioxamine B and E as iron sources on a FhuE- mutant of Escherichia
      coli. This correlated with the production of an additional polypeptide of 70 kDa
      in the outer membrane of E. coli transconjugants, thus confirming that this
      protein serves the ferrioxamine receptor function (FoxR) in E. amylovora.

PMID- 8744898
TI  - Peroxidase deficiency of nickel-transformed hamster cells correlates with their
      increased resistance to cytotoxicity of peroxides.
AB  - Using a procedure aimed at isolation of genes that are inactivated during nickel
      induced carcinogenesis in Chinese hamster cells, a homolog of genes encoding
      human and mouse heme containing peroxidases has been cloned. Northern blot
      analysis of normal cultured fibroblasts and two nickel-transformed cell lines
      confirmed that this gene was expressed in normal but not in transformed cells.
      Nickel-transformed cells also tested negative for peroxidase activity using a
      sensitive fluorescence assay. Cultured embryo cells or fibroblasts that express
      peroxidase activity and their nickel-transformed peroxidase-deficient
      counterparts were employed to investigate the role of peroxidase-catalyzed
      processes in cytotoxicity induced by tert-butyl hydroperoxide or cumene
      hydroperoxide. It has been found that peroxidase-deficient cells were
      significantly more resistant to cytotoxic effect of these compounds suggesting
      that cytotoxic effect of hydroperoxides may be mediated in part by free radicals
      generated in the course of peroxidase-catalyzed reactions.

PMID- 8744899
TI  - Physical and structural characterization of yersiniophore, a siderophore produced
      by clinical isolates of Yersinia enterocolitica.
AB  - Clinical isolates of Yersinia enterocolitca, which belong to mouse-lethal
      serotypes, produce the siderophore yersiniophore. Siderophore production was
      shown to be iron regulated and to reach maximum production in late log phase.
      Yersiniophore is a fluorescent siderophore with maximum excitation at 270 nm and
      a major emission peak at 428 nm. Absorption maxima were seen at 210 and 250 nm
      with a low broad peak from 280 to 320 nm. Purification of unchelated
      yersiniophore for structural analysis was made difficult by low yields (1-2 mg mg
      1), and susceptibility to acid hydrolysis, oxidation and possibly polymerization.
      Yersinophore was therefore purified as an Al3+ chelate, which was found to be
      stable in solution for several weeks. To purify Al(3+)-yersinophore, unchelated
      yersiniophore was first extracted from culture supernatants with dichloromethane,
      concentrated by rotary evaporation and adsorbed to a DEAE-sephacel column. Al(3+)
      yersiniophore was eluted with 0.01 M AlCl3 and further purified by HPLC. The
      structure was established by a combination of elemental analysis, high resolution
      mass spectrometry and two-dimensional NMR experiments. Yersiniophore is a
      phenolate-thiazole siderophore with the formula C21H24N3O4S3Al and a molecular
      weight of 505.07404 when chelated to Al3+. The structure of yersiniophore was
      determined to be closely related to the structures of pyochelin, produced by
      Pseudomonas aeruginosa, and anguibactin, produced by Vibrio anguillarum.

PMID- 8744900
TI  - Liver injury due to iron overload in thalassemia: histopathologic and
      ultrastructural studies.
AB  - The livers of 30 cases of thalassemia (19/beta-thal/HbE, seven thal/HbH and four
      beta-thal major) were studied histopathologically and electron microscopically,
      in an effort to define the morphologic alterations due to iron overload. The
      results of light and electron microscopy were similar in most cases. Iron
      accumulation and fibrosis were the common features found in these patients,
      except that thal/HbH exhibited lesser hepatic damage. The degrees of iron
      deposition and fibrosis were found to be higher in splenectomized and cirrhotic
      than non-splenectomized and non-cirrhotic patients. The subcellular changes were
      swollen mitochondria, with the presence of an electron dense matrix and ruptured
      mitochondrial membrane. Proliferation of smooth endoplasmic reticulum (ER) and
      dilated rough ER was observed. Increases in lysosomal hemosiderin in hepatocytes
      and in Kupffer cells were demonstrated. The possible ways by which the iron
      compounds or free radicals mediated membrane damage are mentioned. The pattern of
      liver cell damage is similar to that of viral hepatitis.

PMID- 8744901
TI  - Purification, spectroscopic analysis and biological activity of the macrocyclic
      dihydroxamate siderophore alcaligin produced by Bordetella pertussis and
      Bordetella bronchiseptica.
AB  - Hydroxamate siderophores of virulent Bordetella pertussis and Bordetella
      bronchiseptica strains were purified using a simple large-scale isolation
      procedure, and identified by various spectroscopic techniques as the macrocyclic
      dihydroxamate siderophore trivially known as alcaligin, 1,8(S),11,18(S)-
      tetrahydroxy-1,6,11,16-tetraazacycloeicosane-2,5,12,15-tetrone+ ++, which was
      previously isolated from the taxonomically-related bacterial species Alcaligenes
      denitrificans subsp. xylosoxydans. Alcaligin purified from iron-depleted cultures
      of B. pertussis and B. bronchiseptica exhibited specific growth-promoting
      activity under iron-restricted conditions for Bordetella indicator strains, and
      ere active in [55Fe]ferric alcaligin transport assays. Evidence suggests that
      several C2-symmetric conformations of alcaligin exist simultaneously in both
      methanolic and aqueous solution.

PMID- 8744902
TI  - Hepatic iron deposition in human disease and animal models.
AB  - Iron deposition occurs in parenchymal cells of the liver in two major defects in
      human subjects (i) in primary iron overload (genetic haemochromatosis) and (ii)
      secondary to anaemias in which erythropolesis is increased (thalassaemia).
      Transfusional iron overload results in excessive storage primarily in cells of
      the reticule endothelial system. The storage patterns in these situations are
      quite characteristic. Excessive iron storage, particularly in parenchymal cells
      eventually results in fibrosis and cirrhosis. There is no animal model or iron
      overload which completely mimics genetics haemochromatosis but dietary iron
      loading with carbonyl iron or ferrocene does produce excessive parenchymal iron
      stores in the rat. Such models have been used to study iron toxicity and the
      action of iron chelators in the effective removal of excessive iron stores.

PMID- 8744903
TI  - Psychological factors in disabling low back pain: causes or consequences?
AB  - Low back pain (LBP) is a common problem that is costly in both financial and
      human terms. The impact of LBP on an individual varies greatly. For some, LBP is
      a minor inconvenience; but for others LBP is associated with significant
      disability and with psychosocial dysfunction for the individual and for the
      family. Whether psychosocial factors are causes or consequences has been the
      subject of debate. This paper is a review of psychosocial factors associated with
      disabling LBP. It addresses the question of whether these factors are causes or
      consequences of the disability due to LBP. Based on this review it was concluded
      that there is little evidence in support of the concept of a pain-prone
      personality. Once LBP has occurred, the impact of the LBP on the individual and
      the family is influenced by the health-beliefs and coping strategies of the
      individual and the family. Distress appears to be secondary to physical
      restriction rather than pain, but the distress may aggravate the pain and thus
      the disability. The paper concludes with a discussion of the impact of health
      practitioners on pain-related disability.

PMID- 8744904
TI  - The Oxfordshire Head Injury Register.
AB  - This paper looks at the process of setting up a Head Injury Register whose aims
      are: (1) to identify reliably and rapidly patients who have sustained a head
      injury so that service can be offered to them; and (2) to obtain epidemiological
      data to identify needs and inform future service planning and development. The
      register records all cases of head injury in patients aged 16-65, regardless of
      severity, which present to hospital services in Oxfordshire whether or not
      admitted as inpatients. It was set up as part of a research project into the
      value of providing an early follow-up service for head injury patients. The paper
      highlights the difficulty of identifying these patients reliably. It details the
      administrative and technological problems encountered, together with some of
      their solutions.

PMID- 8744905
TI  - Reflex sympathetic dystrophy syndrome: diagnosis and treatment.
AB  - The reflex sympathetic dystrophy syndrome is a very common, poorly recognized
      syndrome which is associated with marked disability in some cases. The historical
      aspects, current ideas about the pathogenesis and pathophysiology, clinical
      features and staging are discussed. Early recognition and appropriate
      intervention are the cornerstone of successful treatment and are also discussed.

PMID- 8744906
TI  - Towards a disability-oriented epidemiology of traumatic brain injury.
AB  - The aim of this study was to investigate the value of using a disability-oriented
      approach to the epidemiology of traumatic brain injury (TBI) in order to improve
      health administration by preventing long-term sequelae. The epidemiology of
      disease was established by registration system of inpatients which covers more
      than 99% of all hospital admissions in The Netherlands. Some international
      differences and national trends are discussed. The disability-related
      epidemiology was investigated by means of structured interviews, 3-7 years after
      the injury, in a clustered sample of 51 patients with major TBI according to the
      ICD-9-CM. The survey included evaluation scales such as the Sickness Impact
      Profile, the Barthel Index, and a Disability Rating Questionnaire. Concerning the
      disease-related epidemiological data, the overwhelming majority of all TBI
      patients went home, which suggests good recovery. Nevertheless, the disability
      oriented research revealed long-term situational, cognitive and behavioral
      disabilities in at least 67% of the major-TBI population, whereas only 10%
      received any rehabilitation services at all after the acute-care period. It is
      concluded that preventive measures and a comprehensive service for brain injury
      survivors should be based both on disease and disability-oriented data.

PMID- 8744907
TI  - Vocational achievements following spinal cord injury in Australia.
AB  - This study describes the vocational achievements in a sample (n = 139) of
      Australian persons with spinal cord injuries. The post-accident and employment
      achievements (February-March 1993) were represented by significant diversity in
      outcomes. Around one-third of subjects went on to obtain further qualifications
      since their injury, and around 31% were employed full-time or part-time. The
      majority of subjects utilized informal means of returning to work. Around two
      thirds of those employed indicated that they were in a preferred occupation and
      their median length of employment was 108 months. The hours of work varied
      greatly but were centred around a median of 38 hours (i.e. a full-time job). A
      model of diverse employment outcomes and achievement following spinal cord injury
      is proposed.

PMID- 8744908
TI  - Process over person?: occupational therapy students' fieldwork experiences of
      people in psychiatric settings.
AB  - This paper explores influences of psychiatric service system processes on
      occupational therapy students' understanding of people with psychiatric
      disorders. The fieldwork experiences of 16 occupational therapy undergraduates in
      clinical settings were studied via in-depth interviews and participant
      observation. An important part of the students' understanding of people with
      psychiatric disorders arose from the manner in which the psychiatric service
      system and occupational therapists have structured their dealings with people as
      patients or clients. Students were influenced by system practices such as the
      classification of people as acute/chronic, and a heavy emphasis on quantitative
      performance indicators of services rendered; along with an occupational therapy
      process that may be excessively problem-oriented, at the expense of attending to
      other significant personal and environmental factors within patients'/clients'
      lives. Such circumstances are likely to undermine students' appreciation of the
      humanity and individuality of people using the psychiatric service system.

PMID- 8744909
TI  - The assessment of acute stroke in general medical wards.
AB  - In order to assess the completeness of clinical clerking, a retrospective study
      was made of the medical notes of 194 patients admitted with acute stroke over a 1
      year period. The noting of clinical features associated with disease severity and
      prognosis, such as level of consciousness, proprioception, neglect, mental test
      score and continence was assessed. These features were rarely noted. Factors
      likely to influence placement following recovery were also poorly reported. In
      order to allow an accurate guide to stroke severity and prognosis these factors
      must be noted. An alternative form of clinical clerking is suggested in order to
      improve patient management.

PMID- 8744910
TI  - Introducing alexithymia: a concept within the psychosomatic process.
AB  - Alexithymia (Greek, a = lack, lexis = word, thymos = emotion) is a new concept
      which, whilst being based upon longstanding clinical observation, remains
      unproven clinically. The lack of definite criteria for inclusion, and the absence
      of reliable and valid assessment tools, ensures that past data collection has
      been flawed and that no real inter-study comparisons can be made. However, the
      theoretical concept employed at clinical level provides a personality trait that
      is of great interest to the therapist. Alexithymic individuals lack the ability
      to transfer the emotional (biological) arousal of experience into feelings and
      fantasy that symbolize and express the emotion. Literally, they have no words for
      feeling, and express their arousal in physical (somatic) ways. This paper reviews
      the clinical components of this trait and the somatic symptomatology associated
      with it. It also reviews the present 'tools' for 'measuring' alexithymia, and
      relates these to suggested aetiology. It recommends that all rehabilitation
      personnel should be aware of this phenomenon, as the somatized symptom may be the
      presenting complaint of a client. It also encourages therapists to begin
      screening for alexithymia so that more comprehensive epidemiology information can
      be gathered, particularly relating to the influences on treatment and physical
      manifestation.

PMID- 8744911
TI  - Criteria of good dental practice generated by general dental practitioners and
      patients.
AB  - A survey was carried out asking patients to evaluate the criteria of good dental
      practice proposed by patients and dentists. A total of 344 patients from 4
      different general dental practices in South East England evaluated 16 criteria of
      good dental practice. Eight criteria were generated by 30 general dental
      practitioners and the other eight by 30 patients. Questionnaires containing the 8
      pairs of criteria randomly assigned by a computer were drawn up, with each pair
      containing one patient and one general dental practitioner criterion. Patients
      were asked to indicate their preference. The number of times each criterion was
      preferred was scored and ranked. The three highest ranked criteria were
      explanation of procedures, sterilisation/hygiene and dentist's skills (all
      criteria proposed from patients), whilst the three lowest ranked criteria were up
      to-date equipment, pleasant decor and surroundings and good practice image (all
      criteria proposed from dentists). Overall the criteria proposed by patients as a
      group scored significantly more highly than those proposed by dentists as a
      group. There was variation in rankings relating to the sex, age, pattern of
      attendance and social class of the respondents.

PMID- 8744912
TI  - Clinical evaluation of five adhesive systems: three-year results.
AB  - Five dentine adhesive systems (four resin-based dentine bonding agents and one
      polyacid-modified composite resin) were evaluated clinically in non-undercut
      Class V 'abrasion' lesions. The loss rate of restorations varied from 26 per cent
      to 95 per cent at three years among the five systems. Products which bonded to
      dentine via the hybrid layer were markedly more retentive than those which were
      designed to bond chemically. The two products which attempted to achieve bonding
      between their carboxyl groups and dentinal calcium were hydrophilic, which
      probably contributed to their lack of success.

PMID- 8744913
TI  - An in vitro comparison of micro leakage in three glass ionomer cements used as
      retrograde filling materials.
AB  - The aim of this study was to evaluate the sealing ability of conventional self
      cured glass ionomer cement, silver glass ionomer cement and light-cured glass
      ionomer cement as retrofilling materials. Micro-leakage was assessed by
      introducing the samples into a 1 per cent solution of methylene blue for eight
      days at a constant temperature of 37 degrees C. Dye penetration was greater when
      silver glass ionomer cement was used in comparison to the other two materials
      tested; the difference was statistically significant. Conversely, the sealing
      ability of light-cured glass ionomer cement was significantly higher than that of
      conventional glass ionomer cement. The condition of the dentine-filling material
      interface and the marginal adaptation of the glass ionomer cements under study
      were assessed using scanning electron microscopy.

PMID- 8744915
TI  - A comparison between DAI and SCAN in estimating orthodontic treatment need.
AB  - This study was undertaken to assess the reliability and the correlation between
      two aesthetic indices, the Dental Aesthetic Index (DAI) and the Standardised
      Continuum of Aesthetic Need (SCAN Index) in estimating orthodontic treatment
      priority. The indices were applied to 53 randomly selected study models and
      records of orthodontic patients treated at Mount Vernon Hospital, Middlesex, UK.
      The patients ages at initial presentation ranged from 10.7 to 16.4 years (Mean
      12.8 years, SD 1.0). The DAI and the SCAN Index were moderately correlated (r =
      0.67) and the association was highly statistically significant (p < 0.001). The
      findings indicated that the two indices could be used consistently. The
      limitations of both indices are also discussed.

PMID- 8744914
TI  - Conclusion and review of the Michigan Xylitol Programme (1986-1995) for the
      prevention of dental caries.
AB  - The major results of the Michigan Xylitol Programme (1986-1995) are summarised.
      The Programme consisted of several clinical trials and laboratory investigations
      designed to study the usage of xylitol-containing saliva stimulants in the
      prevention of dental caries. The trials patients included young (initially 6 year
      olds) and adult or geriatric subjects who were given saliva stimulants (mostly
      chewing gum) for periods of two weeks to 56 months. A special rationale behind
      these studies was the need to further test the validity of the 'pentitol-hexitol
      theory' in the prevention of caries. This theory has maintained that pentitols
      (sugar alcohols with five hydroxyl groups, such as xylitol) may be cariologically
      more effective than hexitols (sugar alcohols with six hydroxyl groups, such as
      sorbitol). The accumulated clinical, sialochemical and microbiologic evidence
      suggests that xylitol, a natural carbohydrate sweetener of the pentitol type, is
      more effective in preventing dental caries than sorbitol, and cariologically
      safer than sorbitol, a natural carbohydrate of the hexitol type. Sorbitol was
      found to be significantly less cariogenic than sucrose. The Programme's results
      shed additional light on the cariologic and oral biologic effects of natural,
      dietary polyols, and suggest that the usage of xylitol chewing gum (and in some
      cases xylitol dragees) can be considered a valuable additional tool in caries
      prevention and in stabilisation of caries in all age groups.

PMID- 8744916
TI  - Oral health status of children and adults in Madagascar.
AB  - The present national study was undertaken in order to describe the oral health
      situation of the population in Madagascar. The WHO pathfinder sampling procedures
      were applied to obtain representative samples of the following age groups: 6
      years (n = 1866); 9 years (n = 1905); 12 years (n = 1992); 15 years (n = 1130);
      18 years (n = 792), and 35-44 years (n = 1809). Data were collected in 1993
      according to the methods recommended by WHO, including dental caries, dental
      treatment need, and CPITN. In 6-year-olds, 85 per cent had caries in primary
      teeth and a mean of 3.1 DMFT was observed among the 12 year-olds; the 35-44-year
      olds had an average of 13.1 DMFT. Differences in dental caries prevalence were
      found according to sex, urbanisation, region, and ethnic group. Ninety-one
      percent of individuals at age 18 and 72 per cent at age 35-44 had maximum CPITN
      score 2 (gingival bleeding and calculus). In an African perspective, the oral
      health status of the Malagasy population is extraordinary poor, and the
      implementation of community-based oral health promotion and prevention is
      urgently needed.

PMID- 8744917
TI  - Prevalence of oral lesions in a selected Vietnamese population.
AB  - Clinical examination of the oral and peri-oral regions of a cohort of 550
      Vietnamese living in a refugee camp in Hong Kong was conducted. They comprised
      216 (39 per cent) males and 334 (61 per cent) females and their age ranged from 2
      to 60 years. A positive clinical finding was observed in 14 per cent, 35 males
      and 43 females. The most common condition observed was periapical infection (36
      per cent), either with an abscess or a sinus. Other lesions noted include
      mucocele (10 per cent), traumatic ulcers (9 per cent), tori, either palatal (6
      per cent) or mandibular (3 per cent), lymph node enlargement (7 per cent), pulp
      polyp (6 per cent), angular cheilitis (4 per cent), papillomas (3 per cent),
      cellulitis (3 per cent) and herpes lesions (2 per cent), 7 out of 9 (78 per cent)
      mucoceles were found in females. No malignant lesions were noted.

PMID- 8744918
TI  - The effect of weight loss of liquid on the diametral tensile strengths of various
      kinds of luting cements.
AB  - The role of water evaporation from the liquids of the cements were tested, and
      the effect of this loss on their strength was evaluated for 0, 10, 20 and 30
      minute, intervals. After 30 minutes the evaporation of liquid from the cements
      was so high that they lost their luting consistency. The data suggests that the
      highest weight loss was with polycarboxylate cement liquids, with glass-ionomer
      and zinc phosphate cement liquids following respectively. However, when diametral
      tensile strength test values were evaluated it was determined that glass-ionomer
      exhibited the highest resistance to fracturing and zinc phosphate the lowest.
      Upon examination of samples which were fractured, while polycarboxylate and glass
      ionomer cracked and split into large fragments, zinc phosphate cements fractured
      into a multitude of small pieces. On the basis of this study, it appears that the
      manufacturers' recommendations about the powder-to-liquid ratio and the mixing
      procedures is confirmed particularly and should be adhered to for optimal
      results.

PMID- 8744919
TI  - The effects of near ultraviolet radiation on the toxic effects of polycyclic
      aromatic hydrocarbons in animals and plants: a review.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are common contaminants of terrestrial
      and aquatic ecosystems. Traditional, toxicological studies for defining the
      potential hazard of PAHs in wildlife have been conducted in the absence of UV
      radiation. However, recent toxicology studies particularly in the discipline of
      aquatic toxicology have presented evidence that PAHs may become toxic or
      substantially more toxic upon coexposure to UV light (300-400 nm). In this paper,
      a comprehensive review of the literature pertaining to the toxicological
      interaction of PAHs and UV light in aquatic and terrestrial organisms is
      presented. It is concluded that the acute phototoxic effects of PAHs should be
      considered when conducting environmental risk assessments; however, more research
      needs to be conducted to address the lack of data on the enhancement of UV
      induced carcinogenesis by PAH compounds.

PMID- 8744920
TI  - Effects of the phenoxy herbicide MCPA on SCE frequency and cell kinetics in
      developing chick embryos.

PMID- 8744921
TI  - Design and construction of model stream ecosystems.
AB  - A series of 12 outdoor model stream mesocosms was designed to evaluate the
      effects of chemicals and mixtures on the biota in stream ecosystems. An
      integrated design plan incorporated physical, chemical, and biological factors as
      well as the specific experimental objectives and effects parameters to be
      evaluated. Analysis of biological assemblages such as macroinvertebrates and
      periphyton in the model stream mesocosms demonstrated the presence of diverse and
      sensitive taxa. These model stream mesocosms also included the ability to
      evaluate responses of sentinel fish species such as Pimephales promelas and
      Lepomis macrochirus as well as macrophytes. The design and construction of the
      stream are discussed in detail and a brief description of a typical experimental
      protocol is provided. Experiments, to date, have spanned 14-30 days pretreatment
      "colonization" with 30 days of treatment and 15 days of posttreatment
      observation. Precision and accuracy of test chemical delivery to the stream have
      been excellent and the overall experimental design has been useful for delivering
      threshold toxicity concentrations and evaluating ecosystem potency for the
      chemicals tested.

PMID- 8744922
TI  - Accumulation and physiological and biochemical effects of cadmium in a simple
      aquatic food chain.
AB  - The toxicity of cadmium with regard to the vegetative reproduction of duckweed,
      Lemna gibba, grown in sterile culture, was determined. The EC50 was found to be
      800 ppb. Duckweed grown in 2.24 ppm cadmium (supplied as cadmium nitrate) for 7
      days accumulated 98.5% of the available cadmium from the growth medium. Plants
      that had been grown for 7 days in 2.24 ppm cadmium and control plants were fed to
      red swamp crayfish, Procambarus clarkii, for 14 days. The concentrations of
      cadmium were measured in hepatopancreata and muscles of crayfish on Day 0 and in
      crayfish fed duckweed grown in cadmium for 14 days. Accumulation of this metal in
      hepatopancreata increased 26-fold, i.e., 176.80 ppb on Day 0 to 4657.56 ppb on
      Day 14, and in muscles almost 7-fold, i.e., 6.75 ppb on Day 0 to 46.28 ppb on Day
      14. Crayfish fed cadmium-containing duckweed demonstrated inhibition (55% after
      14 days of feeding) of acetylcholinesterase activity in their central nervous
      tissue compared to crayfish fed cadmium-free duckweed. The ovarian index and
      total lipids content in the ovaries of crayfish fed cadmium-containing duckweed
      demonstrated significant increases on Day 14.

PMID- 8744923
TI  - Distribution of contaminants in aquatic organisms from East Fork Popular Creek.
AB  - The ecological risk assessment of East Fork Poplar Creek (EFPC) in Oak Ridge,
      Tennessee, investigated the nature and magnitude of the observed or expected
      adverse effects of the site's organic and inorganic contaminants on the ecosystem
      structure and function. Aquatic biota such as benthic macroinvertebrates,
      crayfish (Astacidae), redbreast sunfish (Lepomis auritus), and stonerollers
      (Campostoma anomalum), representative of various habitats, were sampled for whole
      body contaminant analysis. The whole-body residue analysis of the representative
      aquatic organisms revealed the presence of over 50 contaminants in varying
      proportions. The relative whole-body distribution of organic contaminants such as
      mixtures of polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and
      pesticides was comparable among the indicator organisms. The relative whole-body
      distribution of inorganic contaminants was, however, less consistent.
      Physicochemical variables characteristic of organic contaminants--such as long
      octanol/water partition coefficient (log KOW), log aqueous solubility, and log
      bioconcentration factors (log BCF), and chemical uptake efficiency (E) unique for
      the organisms sampled for chemical analysis--were used to explain the observed
      whole-body distribution of contaminants in the aquatic organisms from EFPC.

PMID- 8744924
TI  - Safety testing of tebufenozide, a new molt-inducing insecticide, for effects on
      nontarget forest soil invertebrates.
AB  - Tebufenozide, a new molt-inducing insecticide that mimics the action of ecdysone,
      is being considered for use to control defoliating lepidoptera in forests in
      Canada. Soil microcosms, employing substrates and species from the ecosystems in
      which spraying is likely to occur, were used to evaluate the effects of this
      compound on soil invertebrates. The forest earthworm (Dendrobaena octaedra
      Savigny) and four species of Collembola (Folsomia candida Willem, F. nivalis
      (Packard), Onychiurus parvicornis Mills, and Hypogastrura pannosa Macnamara) were
      tested. Survival, growth, and reproduction (cocoon production and viability) in
      the forest earthworm D. octaedra were not affected by exposure to tebufenozide at
      concentrations up to and including 100x expected environmental concentration
      (EEC; equivalent to the operational spray rate; 70 g/ha) in leaf litter over a 10
      week period. Similarly, population growth over 8-10 weeks in the four species of
      soil Collembola in LFH material contaminated with tebufenozide at 100x EEC was
      not affected. Based on the results of these (limited) tests, it therefore appears
      that, under normal operational conditions, tebufenozide should not pose a hazard
      to soil invertebrates. The selection of appropriate test species and systems for
      forestry applications is discussed.

PMID- 8744925
TI  - Acute toxicity of fire control chemicals to Daphnia magna (Straus) and
      Selenastrum capricornutum (Printz).
AB  - Acute toxicity tests were conducted exposing Daphnia magna Straus (daphnid) in
      soft and hard reconstituted waters (hardness 42 and 162 mg/liter as CaCO3,
      respectively), and Selenastrum capricornutum Printz (algae) in ASTM algal assay
      medium (hardness 15 mg/liter as CaCO3) to fire retardants Fire-Trol GTS-R, Fire
      Trol LCG-R, and Phos-Chek D75-F, and foam suppressants Phos-Check WD-881 and Silv
      Ex. The chemicals were slightly toxic to practically harmless to daphnids and
      moderately toxic to algae. Water quality did not consistently alter the toxicity
      of the test chemicals to daphnids. The most toxic chemical to daphnids was Silv
      Ex (48-hr EC50 7 mg/liter in soft and hard waters), whereas the least toxic
      chemical to daphnids was Fire-Trol LCG-R (48-hr EC50 848 mg/liter in soft water,
      813 mg/liter in hard water). The most toxic chemical to algae was Fire-Trol LCG-R
      (96-hr IC50 10 mg/liter), and the least toxic chemical was Phos-Chek D75-F (96-hr
      IC50 79 mg/liter). Un-ionized ammonia concentrations near the EC50 or IC50 value
      in tests with the Fire-Trol compounds were frequently equal to or above reported
      LC50 un-ionized ammonia concentrations. Un-ionized ammonia concentrations in
      tests with Phos-Chek D75-F were low, thus other toxic components present in the
      compounds probably contributed to the toxicity. When compared to the daphnids
      tested in ASTM soft water, the Fire-Trol compounds were most toxic to algae,
      whereas Phos-Chek D75-F and the foam suppressants were most toxic to daphnids.
      The results of these tests are comparable to those obtained from research
      conducted in other laboratories with the same species and similar chemicals.
      Accidental entry of fire-fighting chemicals into aquatic environments could
      adversely affect algae and aquatic invertebrates, thus disrupting ecosystem
      function.

PMID- 8744926
TI  - Photoinduced effects of polycyclic aromatic hydrocarbons on Brassica napus
      (Canola) during germination and early seedling development.
AB  - It has recently been demonstrated that light dramatically enhances the toxicity
      of polycyclic aromatic hydrocarbons (PAHs) to the duckweed Lemna gibba L. G-3 (L.
      Ren, X.-D. Huang, B.J. McConkey, D.G. Dixon, and B.M. Greenberg, 1994,
      Ecotoxicol. Environ. Saf. 28, 160-171). To extend this research to terrestrial
      plants, Brassica napus L. (oil seed rape) seeds were germinated in the presence
      of three PAHs; anthracene (ANT), benzo[a]pyrene (BAP), and fluoranthene. The
      chemicals were applied both in intact form and following photomodification in UV
      B radiation; toxicity was assessed in simulated solar radiation (SSR), a light
      source with a visible light:UV-A:UV-B ratio similar to that of sunlight.
      Germination efficiency, root and shoot growth, and chlorophyll content, measured
      after 6 days of exposure, were used as toxicity endpoints. Intact and
      photomodified PAHs had little impact on shoot fresh weight or chlorophyll
      content, but markedly inhibited root fresh weight, with the photomodified PAHs
      having greater impacts than the intact PAHs. The decline in root fresh weight was
      not attributable to a decline in germination frequency or delayed germination.
      However, the seedlings produced shorter roots in the presence of either intact or
      photomodified PAHs. To explore the role of actinic radiation on PAH toxicity,
      seedlings were incubated in SSR, visible light and darkness with either intact or
      photomodified PAHs. Inhibition of root growth was only achieved by the intact
      chemicals if actinic radiation was present. However, with photomodified ANT or
      photomodified BAP, root fresh weight accumulation was inhibited in SSR, visible
      light and darkness. Thus, intact PAHs are hazardous to terrestrial plants in the
      presence of light, but once the compounds are photomodified, actinic radiation is
      no longer an absolute requirement for phytotoxic activity.

PMID- 8744928
TI  - Evaluation of respirometric data: identification of features that preclude data
      fitting with existing kinetic expressions.
AB  - The use of respirometric for from the evaluation of intrinsic biodegradation
      kinetic parameters for single organic compounds is discussed. Emphasis is placed
      on the preliminary assessment of the data set to determine whether it is suitable
      for kinetic parameter estimation. Careful preliminary examination of the data
      avoids attempting parameter estimation with unacceptable data. Furthermore, the
      use of unbiased respirometric data helps ensure that the estimated parameters
      truly reflect the intrinsic kinetics for biodegradation of a single substrate by
      the culture tested. Both experimental and theoretical oxygen uptake curves are
      used to illustrate how various conditions can limit the utility of a given data
      set. The effect of substrate inhibition, dual or multiple substrate limited
      growth, inaccuracies in the initial conditions assumed for curve fitting, and the
      use of poorly acclimated cultures are discussed. Techniques are presented which
      allow identification of whether a data set is unsuitable and should not be used
      for parameter estimation. In addition, experimental procedures which can help
      avoid the collection of aberrant data are discussed.

PMID- 8744927
TI  - Biomarker assessment of the effects of petroleum refinery contamination on
      channel catfish.
AB  - A suite of biomarkers was used to evaluate acute (1- and 7-day) heavy metal
      induced toxicity in channel catfish, Ictalurus punctatus, caged at an abandoned
      petroleum refinery and a non-contaminated reference site. Assays performed
      include indicators of metabolic, hematological, osmoregulatory, and genotoxic
      stress. Two cage designs were utilized to evaluate the importance of exposure
      routes: one allowing exclusive contact with the water column and the other
      allowing contact with water and sediments. Data collected at 1 and 7 days
      postexposure indicated that the experimental fish were stressed, having
      significant increases in blood glucose. After 7 days of exposure, two hemodynamic
      parameters, hemoglobin and delta-aminolevulinic acid dehydratase, were
      significantly increased. There were no significant differences observed in other
      parameters measured.

PMID- 8744929
TI  - Safety assessment based on irrelevant toxicologic data: an extraordinary case of
      bromomethane used as a fumigant.
AB  - Bromomethane (BM) is a fumigant used in agriculture; it readily breaks down to
      bromide ion. WHO assessed the ADI of BM, at 1 mg/kg, using data on the toxicity
      of bromide. On the other hand, U.S. EPA used the observation of hyperplasia in
      the forestomach of rats given BM by gavage and arrived at a value of 0.0014
      mg/kg. The validity of EPA's assessment is thus subject to question because of
      the data involved by (1) direct introduction of this volatile and reactive
      chemical to the GI by gavage and (2) using lesions in the rat forestomach which
      is absent in humans.

PMID- 8744930
TI  - Spheroid cultures of human hepatoblastoma cells (HuH-6 line) and their
      application for cytotoxicity assay of alcohols.
AB  - Spheroid cultures of human hepatoblastoma cells (HuH-6 line) were established by
      rotating 3 x 10(6) cells/3 ml culture medium in 25-ml Erlenmeyer flasks on a
      gyratory shaker. The size of the spheroids rapidly increased until 4 days of
      culture, and thereafter their size gradually increased until 8 days of culture. A
      considerable amount of lactate dehydrogenase (LDH) was detected in the culture
      medium at 24h after seeding because of cell damage by subculturing, but
      thereafter the amount released was small, indicating that the spheroids were in
      healthy condition. Albumin production, one of the differentiated functions of
      hepatocytes, was higher in spheroid cultures than in monolayer cultures. Using
      this spheroid culture model, the cytotoxic effects of alcohols on HuH-6 cells
      were studied by measuring the activity of LDH released in the medium from damaged
      cells. The results indicate that the increasing order of toxicity of the alcohols
      was as follows: methanol < ethanol < propanol.

PMID- 8744931
TI  - Availability of liposomes as drug carriers to the brain.
AB  - Phospholipid vesicles, also known as liposomes, were examined for their ability
      to act as a drug carrier to the brain. 9-Amino-1,2,3,4-tetrahydroacridine (THA),
      a centrally acting acetylcholinesterase inhibitor, was used as a model drug. THA
      was encapsulated in dehydration-rehydration vesicles (DRV) composed of egg yolk
      phosphatidylcholine, cholesterol and dipalmitoyl-phosphatidic acid (molar ratio,
      10/10/1) and injected into the heart of mice. The toxicity and side effects of
      THA were reduced by encapsulation in liposomes. The THA concentration in the
      mouse brain after injection of THA-encapsulated DRV at a dose of 2 mg/kg remained
      higher than that of free THA at the same dose. Effective concentration of THA in
      the brain was also prolonged by the use of liposomes, although accumulation of
      THA in the spleen and kidney was observed. We, therefore, concluded that
      liposomes are useful as carriers of drugs to the brain.

PMID- 8744933
TI  - Pancreaticogastrostomy: effect of partial gastrectomy on the pancreatic stump in
      rabbits.
AB  - To assess the influence of digestive juice on the pancreatic stump when
      pancreaticogastrostomy was performed after pancreatoduodenectomy, the pancreatic
      stump was anastomosed to the intact stomach (group I), the stomach after partial
      gastrectomy (group II), or the jejunum (group III) in rabbits, and the nature of
      the digestive juice at the anastomotic site as well as the histologic changes of
      the pancreatic tissue were investigated. The digestive juice was highly acidic in
      group I, slightly acidic in group II, and almost neutral in group III.
      Histological examination of the pancreatic stump revealed extensive coagulative
      necrosis and delayed replacement with granulation tissue in group I, while there
      was less prominent liquefactive necrosis and early replacement with granulation
      tissue in groups II and III. Intraperitoneal abscess formation around the
      anastomotic site and atrophic fibrosis of the pancreas (similar to the changes
      after pancreatic duct ligation) occurred in 27.8% and 46.2% of group I rabbits,
      respectively, but no such changes were detected in groups II and III (both P <
      0.05). These results indicate that the highly acidic gastric juice had a
      widespread corrosive effect on the anastomosed pancreatic tissue, and that
      partial gastrectomy may be necessary to prevent anastomotic leakage and
      pancreatic duct obstruction after pancreaticogastrostomy.

PMID- 8744932
TI  - Cloning of cDNA with possible transcription factor activity at the G1-S phase
      transition in human fibroblast cell lines.
AB  - Normal human fibroblasts have a finite proliferative capacity in vitro. Thus,
      immortalization of human cells is associated with cellular aging. We have
      established an immortalization-sensitive cell line from fibroblasts of Wilms'
      tumor patients which have a partial deletion of chromosome 1 1p. This cell line
      was easily immortalized by introducing SV4OT. By differential hybridization using
      both SV4OT-introduced crisis cells and young cells, we cloned a gene that was
      highly expressed in 1 1p-cells at the time of the crisis and named this gene C-1.
      Nucleotide sequence analysis of C-1 revealed that it contains a helix-loop-helix
      domain, indicating that it may be a transcription factor. Expression of the C-1
      gene was transiently induced early in the G0-to-S phase transition in two normal
      human (OUMS-24 and HSF-412) and a non-tumorigenic immortal human (OUMS-24F)
      fibroblast cell lines, while the other immortal SUSM-1 cells highly expressed the
      C-1 gene in the middle G1 phase. These results suggest that the C-1 gene product
      may function as a transcription factor related to the cell cycle.

PMID- 8744934
TI  - Detection of Epstein-Barr virus RNA and related antigens in non-neoplastic
      lymphoid lesions.
AB  - To elucidate the latent state and reactivation of Epstein-Barr virus (EBV) in non
      neoplastic lymphoid lesions, we investigated 144 non-neoplastic lymphoid lesions
      by in situ hybridization (ISH) to detect the expression of EBV-encoded small RNAs
      (EBER)-1 and BCRF-1 and by immunostaining for latent membrane protein (LMP)-1 and
      ZEBRA. ISH for EBER-1 detected EBER-1-positive cells (EPC) in 31 of the 144
      examined lesions (22%). EPC were detected in 4 of 49 cases of nonspecific
      lymphoid hyperplasia, in 16 of 20 abscess-forming granulomatous lymphadenitis
      (AFGL), 5 of 25 Kikuchi's disease, and in 3 of 3 infectious mononucleosis. LMP-1
      was expressed in 6 of 124 non-neoplastic lymphoid lesions (4.8%). LMP-1-positive
      cells were observed in 6 of the 31 EBER-1-positive cases (19%). EPC were detected
      significantly more frequently in LMP-1- and ZEBRA-positive specimens than in the
      LMP-1- and ZEBRA-negative specimens. BCRF-1 was expressed in 4 of 11 cases
      examined: 2 of 3 AFGL, 1 of 2 Kikuchi's disease, and in the 1 case of atypical
      lymphoid hyperplasia. This study suggests that Epstein-Barr virus is prevalent
      and can be reactivated in the lymph nodes effaced by destructive inflammation,
      such as AFGL. Such inflammation may provide a local milieu that is conducive for
      EBV to enter the lytic cycle.

PMID- 8744935
TI  - Postoperative gastric motility, secretory function, and pre- and postoperative
      carbohydrate metabolic states in esophageal cancer patients.
AB  - This study was undertaken to assess postoperative gastric motility and gastric
      acid secretion, and pre- and postoperative carbohydrate metabolism in patients
      with esophageal cancer. The gastric motility was compared among 3 different
      reconstruction routes in 26 patients who were divided into 2 groups according to
      the duration of postoperative follow-up; group A, 3 months or less; and group B,
      18 months or more. The routes used for subtotal resection of the stomach were the
      posterior mediastinal, retrosternal, and subcutaneous routes. All patients showed
      positive resting pressure in the esophagus, but peristaltic waves did not reach
      the gastric tube at dry swallowing in any patients and peristaltic waves appeared
      after eating pudding only in 1 patient in group B. The resting pressure and
      gastric emptying time were similar among reconstruction routes, but the incidence
      and amplitude of metoclopramide (MCP)-induced peristaltic waves were
      significantly higher in group B than in group A. Furthermore, 24-h intragastric
      pH monitoring of gastric secretion in a group of 9 patients revealed individual
      variation in gastric secretion. Some patients showed high acidity soon after
      operation, suggesting the need for prophylactic treatment for preventing gastric
      ulcer. Postoperatively, postprandial serum gastrin levels were significantly
      higher than preoperative levels. In the other group of 11 patients tested,
      preoperative and postoperative carbohydrate metabolism were not significantly
      different. Postoperatively, carbohydrate metabolism recovered to preoperative
      levels after a transient decrease. These results demonstrated that postoperative
      motility improved over time although no difference was found among the 3
      reconstruction routes used.

PMID- 8744936
TI  - Blood glucose levels in hypertensive patients during treatment with different
      antihypertensive agents.
AB  - Fasting blood glucose was determined in 27 adults with essential hypertension at
      four different periods during a 12-month treatment with doxazosin, an alpha
      adrenoceptor antagonist, and in another set of 20 adult hypertensive patients,
      after 3 months treatment with amlodipine, a calcium antagonist. The mean fasting
      blood glucose levels at various determinations during doxazosin therapy did not
      show any significant variation from the pre-treatment value. Similarly, mean
      fasting blood glucose level remained the same after 3 months of amlodipine
      therapy. The findings, therefore, highlights the safety of doxazosin and
      amlodipine antihypertensive pharmacotherapies.

PMID- 8744937
TI  - Femoral neck fracture following avascular necrosis of the femoral head.
AB  - Four cases of femoral neck fracture following avascular necrosis of the femoral
      head were studied histologically. All four patients were women who had received
      steroid therapy, three of them for systemic lupus erythematosus and the other for
      idiopathic thrombocytopenic purpura. Two types of fracture were found according
      to the site and the mechanism of fracture. One was at the junction between the
      necrotic bone and the repairing bone, and it can thus be regarded as a stress
      fracture. The other type of fracture commenced at the superior portion of the
      junction between the femoral head and neck, which was weak due to the repair
      reaction. The fracture line extended to the inferior cortex of the femoral neck,
      as often occurs in the elderly. In one patient, the femoral neck fracture was the
      first sign of avascular necrosis of the femoral head.

PMID- 8744938
TI  - Application of computers in diabetes care--a review. I. Computers for data
      collection and interpretation.
AB  - The paper reviews the contribution of information technology (IT) to diabetes
      care. An appraisal of this topic with respect to insulin-dependent (type 1)
      diabetic patients is carried out in view of the landmark findings of the Diabetes
      Control and Complications Trial (DCCT) which has demonstrated that maintaining
      tight blood glucose control can delay the onset and slow the progression of the
      later life complications of diabetes. The review starts with the clinical
      background and the main features of the control schema in which diabetic patients
      receive insulin therapy. An overview is then provided of recent IT initiatives in
      diabetes care, and the application of IT techniques to assist in the diagnosis
      and characterization of patients with diabetes mellitus is considered. The role
      of IT approaches for short-term glycaemic control is discussed and the
      utilization of computers for collecting, viewing and interpreting home monitoring
      blood glucose data is reviewed; both quantitative and qualitative techniques
      being considered. In the second paper the role of decision support tools for
      planning insulin therapy using clinical algorithms, hand-held devices, knowledge
      based approaches, telemedicine techniques and interactive simulations is
      reviewed, and the validation and clinical evaluation of these tools is discussed.
      The likely impact of the routine clinical application of implantable/non-invasive
      blood glucose monitoring devices is also considered. Finally, the application of
      computers as teaching tools is reviewed and the ways in which such educational
      approaches might be applied for disseminating the benefits of the DCCT trial more
      widely are discussed.

PMID- 8744939
TI  - Application of computers in diabetes care--a review. II. Computers for decision
      support and education.
AB  - This paper concludes a review of the contribution of information technology to
      diabetes care. The role of decision support tools for planning insulin therapy
      using various clinical algorithms, knowledge-based approaches and interactive
      simulations is discussed, and certain telemedicine approaches to therapy are
      considered. The validation and clinical evaluation of these tools is reviewed, as
      is the likely impact of the routine clinical application of implantable/non
      invasive blood glucose monitoring devices. Finally, the application of computers
      as teaching tools is considered, and ways in which such educational approaches
      might be applied for disseminating the benefits of the Diabetes Control and
      Complications Trial more widely are discussed.

PMID- 8744940
TI  - Essential data set for computer management of distributed primary care services.
AB  - Reported here is a personal computer-based registration program of medical
      consultations in general practice that has been implemented in six communities
      ('primary health care districts'; total population 112623) in the county of
      Jonkoping, southern Sweden. The program enabled decentralized monitoring and
      management of the primary health care organization in the communities. The
      objective of the present paper is to give, from one year's experience of about
      137000 recorded visits, a broad overview of the program structure, briefly
      considering the questions associated with routine registration of medical
      consultations, to discuss how the system is used for decision and steering
      support as well as to summarize its overall performance, results and costs in
      relation to the general utility of accurate information on health service
      delivery and consumption in the population.

PMID- 8744941
TI  - Multimedia search system for a textbook of urology in Japanese.
AB  - A search system for the textbook of urology has been developed and evaluated. The
      textbook is written in Japanese with 1.4 megabytes of text and has about 1000
      pictures. The contents of the textbook can be seen with English or Japanese
      medical terms. The system contains a dictionary of Japanese medical terms. The
      dictionary has a network structure based on Japanese ideographic characters. Such
      a search system is useful for physicians because of its speed and the widely
      spread medical knowledge of many authors of the textbook.

PMID- 8744942
TI  - Use of neural networks in medical expert systems.
AB  - A prototype Expert System, able to assist gynaecologists in diagnosing and
      classifying cancer of the neck of the womb is designed and implemented. The
      system is implemented using NeuroShell, an Expert System Building Tool, based on
      Neural Networks. A neural model, which predicts the possible outcomes of
      colposcopy and biopsy, based on Pap test results, as well as on information from
      the patient record, is developed. Such a system is a very useful tool for
      physicians both as a training tool as well as a forecasting system, while it also
      has the capability of incorporating new knowledge, provided by each new case it
      is presented with. Furthermore, a number of different implementations are
      provided in order to evaluate a comparative study of their performance.

PMID- 8744943
TI  - Identification of the cysteine residues involved in the class I disulfide bonds
      of the human insulin receptor: properties of insulin receptor monomers.
AB  - The cysteine residues involved in the class I disulfide bonds between the alpha
      subunits in the (alpha beta)2 dimer of the human insulin receptor have been
      identified by labeling with N-ethylmaleimide and by site-directed mutagenesis.
      Both cysteine 524 and cysteine 682 form interchain disulfide bonds; their
      conversion to serine residues results in the absence of receptor dimers and the
      presence of alpha beta monomers. The receptor monomers have a slightly lower
      affinity for insulin than the native receptor dimers. Insulin binding to the
      receptor monomers promotes their dimerization in the plasma membrane; at
      nanomolar concentrations of receptor, both unliganded and liganded receptors are
      monomers. Receptor monomers are stimulated by insulin to autophosphorylate and to
      phosphorylate exogenous subtrates with the same efficiency as the receptor
      dimers. The conclusion is that receptor dimerization is not required to activate
      the tyrosine kinase activity of the insulin receptor.

PMID- 8744944
TI  - Domains of alpha-SNAP required for the stimulation of exocytosis and for N
      ethylmalemide-sensitive fusion protein (NSF) binding and activation.
AB  - The binding of alpha-SNAP to the membrane proteins syntaxin, SNAP-25, and
      synaptobrevin leads to the recruitment of the N-ethylmaleimide-sensitive fusion
      protein (NSF). ATP hydrolysis by NSF has been suggested to drive conformational
      changes in one or more of these membrane proteins that are essential for
      regulated exocytosis. Functional evidence for a role of alpha-SNAP in exocytosis
      in adrenal chromaffin cells comes from the ability of this protein to stimulate
      Ca(2+)-dependent exocytosis in digitonin-permeabilized cells. Here we examine the
      effect of a series of deletion mutants of alpha-SNAP on exocytosis, and on the
      ability of alpha-SNAP to interact with NSF, to define essential domains involved
      in protein-protein interactions in exocytosis. Deletion of extreme N- or C
      terminal regions of alpha-SNAP produced proteins unable to bind to syntaxin or to
      stimulate exocytosis, suggesting that these domains participate in essential
      interactions. Deletion of C-terminal residues abolished the ability of alpha-SNAP
      to bind NSF. In contrast, deletion of up to 120 N-terminal residues did not
      prevent the binding of NSF to immobilized alpha-SNAP and such mutants were also
      able to stimulate the ATPase activity of NSF. These results suggest that the C
      terminus, but not the N-terminus, of alpha-SNAP is crucial for interactions with
      NSF. The involvement of the C-terminus of alpha-SNAP, which contains a predicted
      coiled-coil domain, in the binding of both syntaxin and NSF would place the
      latter two proteins in proximity in a ternary complex whereupon the energy
      derived from ATP hydrolysis by NSF could induce a conformational change in
      syntaxin required for exocytosis to proceed.

PMID- 8744945
TI  - Distinct roles of yeast MEC and RAD checkpoint genes in transcriptional induction
      after DNA damage and implications for function.
AB  - In eukaryotic cells, checkpoint genes cause arrest of cell division when DNA is
      damaged or when DNA replication is blocked. In this study of budding yeast
      checkpoint genes, we identify and characterize another role for these checkpoint
      genes after DNA damage-transcriptional induction of genes. We found that three
      checkpoint genes (of six genes tested) have strong and distinct roles in
      transcriptional induction in four distinct pathways of regulation (each defined
      by induction of specific genes). MEC1 mediates the response in three
      transcriptional pathways, RAD53 mediates two of these pathways, and RAD17
      mediates but a single pathway. The three other checkpoint genes (including RAD9)
      have small (twofold) but significant roles in transcriptional induction in all
      pathways. One of the pathways that we identify here leads to induction of MEC1
      and RAD53 checkpoint genes themselves. This suggests a positive feedback circuit
      that may increase the cell's ability to respond to DNA damage. We make two
      primary conclusions from these studies. First, MEC1 appears to be the key
      regulator because it is required for all responses (both transcriptional and cell
      cycle arrest), while other genes serve only a subset of these responses. Second,
      the two types of responses, transcriptional induction and cell cycle arrest,
      appear distinct because both require MEC1 yet only cell cycle arrest requires
      RAD9. These and other results were used to formulate a working model of
      checkpoint gene function that accounts for roles of different checkpoint genes in
      different responses and after different types of damage. The conclusion that the
      yeast MEC1 gene is a key regulator also has implications for the role of a
      putative human homologue, the ATM gene.

PMID- 8744946
TI  - Expression and activity of serum response factor is required for expression of
      the muscle-determining factor MyoD in both dividing and differentiating mouse
      C2C12 myoblasts.
AB  - To understand the mechanism by which the serum response factor (SRF) is involved
      in the process of skeletal muscle differentiation, we have assessed the effect of
      inhibiting SRF activity or synthesis on the expression of the muscle-determining
      factor MyoD. Inhibition of SRF activity in mouse myogenic C2C12 cells through
      microinjection of either the SRE oligonucleotide (which acts by displacing SRF
      proteins from the endogenous SRE sequences), purified SRF-DB (a 30-kDa portion of
      SRF containing the DNA-binding domain of SRF, which acts as a dominant negative
      mutant in vivo), or purified anti-SRF antibodies rapidly prevents the expression
      of MyoD. Moreover, the rapid shutdown of MyoD expression after in vivo inhibition
      of SRF activity is observed not only in proliferating myoblasts but also in
      myoblasts cultured under differentiating conditions. Additionally, by using a
      cellular system expressing a glucocorticoid-inducible antisense-SRF (from aa 74
      to 244) we have shown that blocking SRF expression by dexamethasone induction of
      antisense SRF results in the lack of MyoD expression as probed by both
      immunofluorescence and Northern blot analysis. Taken together these data
      demonstrate that SRF expression and activity are required for the expression of
      the muscle-determining factor MyoD.

PMID- 8744947
TI  - p150Glued, the largest subunit of the dynactin complex, is nonessential in
      Neurospora but required for nuclear distribution.
AB  - Dynactin is a multisubunit complex that is required for cytoplasmic dynein, a
      minus-end-directed, microtubule-associated motor, to efficiently transport
      vesicles along microtubules in vitro. p150Glued, the largest subunit of dynactin,
      has been identified in vertebrates and Drosophila and recently has been shown to
      interact with cytoplasmic dynein intermediate chains in vitro. The mechanism by
      which dynactin facilitates cytoplasmic dynein-dependent vesicle transport is
      unknown. We have devised a genetic screen for cytoplasmic dynein/dynactin mutants
      in the filamentous fungus Neurospora crassa. In this paper, we report that one of
      these mutants, ro-3, defines a gene encoding an apparent homologue of p150Glued,
      and we provide genetic evidence that cytoplasmic dynein and dynactin interact in
      vivo. The major structural features of vertebrate and Drosophila p150Glued, a
      microtubule-binding site at the N-terminus and two large alpha-helical coiled
      coil regions contained within the distal two-thirds of the polypeptide, are
      conserved in Ro3. Drosophila p150Glued is essential for viability; however, ro-3
      null mutants are viable, indicating that dynactin is not an essential complex in
      N. crassa. We show that N. crassa cytoplasmic dynein and dynactin mutants have
      abnormal nuclear distribution but retain the ability to organize cytoplasmic
      microtubules and actin in anucleate hyphae.

PMID- 8744948
TI  - Osteopontin stimulates gelsolin-associated phosphoinositide levels and
      phosphatidylinositol triphosphate-hydroxyl kinase.
AB  - Based on previous studies demonstrating activation of phosphatidylinositol 3
      hydroxyl kinase (PI3-kinase) and stimulation of a change in cell shape, we
      examined the effect of osteopontin on the association of phospholipids with
      gelsolin, an actin-capping/severing protein. Osteopontin stimulated a rapid
      increase in phosphatidylinositol bisphosphate and phosphatidylinositol
      triphosphate levels associated with gelsolin in Triton-soluble fractions of cell
      lysates. The increased levels of phosphatidylinositol triphosphate associated
      with gelsolin were due to stimulation of PI3-kinase activity associated with
      gelsolin in the Triton-soluble fractions, and they were blocked by the PI3-kinase
      inhibitor wortmannin. Osteopontin stimulated translocation of PI3-kinase from the
      Triton-insoluble to Triton-soluble gelsolin. Osteopontin also decreased Triton
      soluble gelsolin/actin complexes consistent with actin uncapping, and increased F
      actin levels, which were also blocked by wortmannin. The osteopontin effects were
      mediated through binding to the alpha(v)beta 3 integrin. Taken together, our
      studies indicate that osteopontin/alpha(v)beta 3-mediated changes in gelsolin
      associated phosphoinositide levels and PI3-kinase activity are related to
      stimulation of F-actin formation in osteoclasts.

PMID- 8744949
TI  - Differential replication and DNA elimination in the polytene chromosomes of
      Euplotes crassus.
AB  - The transposon-like Tec elements of Euplotes crassus are precisely excised during
      formation of polytene chromosomes in the developing macronucleus. To determine
      whether all Tec elements exhibit identical developmental timing of excision, we
      used polymerase chain reaction to visualize amplification and diminution at
      numerous randomly selected Tec insertion sites. Two classes of sites are evident.
      Early replicating sites show one or more rounds of amplification and diminution
      (corresponding to excision) and frequently occur within macronuclear-destined
      sequences. Late replicating sites do not undergo diminution until chromosome
      fragmentation and are predominantly associated with eliminated sequences. We
      conclude that the previously described clustering of macro-nuclear-destined
      sequences in the micronuclear genome allows for their differential replication at
      the polytene stage and results in targeting of these sequences for
      transcriptional activation and highly specific deletion and chromosome
      fragmentation processes.

PMID- 8744950
TI  - Different subcellular localization of Saccharomyces cerevisiae HMG-CoA reductase
      isozymes at elevated levels corresponds to distinct endoplasmic reticulum
      membrane proliferations.
AB  - In all eucaryotic cell types analyzed, proliferations of the endoplasmic
      reticulum (ER) can be induced by increasing the levels of certain integral ER
      proteins. One of the best characterized of these proteins is HMG-CoA reductase,
      which catalyzes the rate-limiting step in sterol biosynthesis. We have
      investigated the subcellular distributions of the two HMG-CoA reductase isozymes
      in Saccharomyces cerevisiae and the types of ER proliferations that arise in
      response to elevated levels of each isozyme. At endogenous expression levels,
      Hmg1p and Hmg2p were both primarily localized in the nuclear envelope. However,
      at increased levels, the isozymes displayed distinct subcellular localization
      patterns in which each isozyme was predominantly localized in a different region
      of the ER. Specifically, increased levels of Hmg1p were concentrated in the
      nuclear envelope, whereas increased levels of Hmg2p were concentrated in the
      peripheral ER. In addition, an Hmg2p chimeric protein containing a 77-amino acid
      lumenal segment from Hmg1p was localized in a pattern that resembled that of
      Hmg1p when expressed at increased levels. Reflecting their different subcellular
      distributions, elevated levels of Hmg1p and Hmg2p induced sets of ER membrane
      proliferations with distinct morphologies. The ER membrane protein, Sec61p, was
      localized in the membranes induced by both Hmg1p and Hmg2p green fluorescent
      protein (GFP) fusions. In contrast, the lumenal ER protein, Kar2p, was present in
      Hmg1p:GFP membranes, but only rarely in Hmg2p:GFP membranes. These results
      indicated that the membranes synthesized in response to Hmg1p and Hmg2p were
      derived from the ER, but that the membranes were not identical in protein
      composition. We determined that the different types of ER proliferations were not
      simply due to quantitative differences in protein amounts or to the different
      half-lives of the two isozymes. It is possible that the specific distributions of
      the two yeast HMG-CoA reductase isozymes and their corresponding membrane
      proliferations may reveal regions of the ER that are specialized for certain
      branches of the sterol biosynthetic pathway.

PMID- 8744951
TI  - TPR proteins required for anaphase progression mediate ubiquitination of mitotic
      B-type cyclins in yeast.
AB  - The abundance of B-type cyclin-CDK complexes is determined by regulated synthesis
      and degradation of cyclin subunits. Cyclin proteolysis is required for the final
      exit from mitosis and for the initiation of a new cell cycle. In extracts from
      frog or clam eggs, degradation is accompanied by ubiquitination of cyclin. Three
      genes, CDC16, CDC23, and CSE1 have recently been shown to be required
      specifically for cyclin B proteolysis in yeast. To test whether these genes are
      required for cyclin ubiquitination, we prepared extracts from G1-arrested yeast
      cells capable of conjugating ubiquitin to the B-type cyclin Clb2. The
      ubiquitination activity was cell cycle regulated, required Clb2's destruction
      box, and was low if not absent in cdc16, cdc23, cdc27, and cse1 mutants.
      Furthermore all these mutants were also defective in ubiquitination of another
      mitotic B-type cyclin, Clb3. The Cdc16, Cdc23, and Cdc27 proteins all contain
      several copies of the tetratricopeptide repeat and are subunits of a complex that
      is required for the onset of anaphase. The finding that gene products that are
      required for ubiquitination of Clb2 and Clb3 are also required for cyclin
      proteolysis in vivo provides the best evidence so far that cyclin B is degraded
      via the ubiquitin pathway in living cells. Xenopus homologues of Cdc16 and Cdc27
      have meanwhile been shown to be associated with a 20S particle that appears to
      function as a cell cycle-regulated ubiquitin-protein ligase.

PMID- 8744952
TI  - Re-expression of ABP-120 rescues cytoskeletal, motility, and phagocytosis defects
      of ABP-120- Dictyostelium mutants.
AB  - The actin binding protein ABP-120 has been proposed to cross-link actin filaments
      in nascent pseudopods, in a step required for normal pseudopod extension in
      motile Dictyostelium amoebae. To test this hypothesis, cell lines that lack ABP
      120 were created independently either by chemical mutagenesis or homologous
      recombination. Different phenotypes were reported in these two studies. The
      chemical mutant shows only a subtle defect in actin cross-linking, while the
      homologous recombinant mutants show profound defects in actin cross-linking,
      cytoskeletal structure, pseudopod number and size, cell motility and chemotaxis
      and, as shown here, phagocytosis. To resolve the controversy as to what the ABP
      120- phenotype is, ABP-120 was re-expressed in an ABP-120- cell line created by
      homologous recombination. Two independently "rescued" cell lines that express
      wild-type levels of ABP-120 were analyzed. In both rescued cell lines, actin
      incorporation into the cytoskeleton, pseudopod formation, cell morphology,
      instantaneous velocity, phagocytosis, and chemotaxis were restored to wild-type
      levels. There is no alteration in the expression levels of several related actin
      binding proteins in either the original ABP-120- cell line or in the rescued cell
      lines, leading to the conclusion that neither the aberrant phenotype observed in
      ABP-120- cells nor the normal phenotype reasserted in rescued cells can be
      attributed to alterations in the levels of other abundant and related actin
      binding proteins. Re-expression of ABP-120 in ABP-120- cells reestablishes normal
      structural and behavioral parameters, demonstrating that the severity and
      properties of the structural and behavioral defects of ABP-120- cell lines
      produced by homologous recombination are the direct result of the absence of ABP
      120.

PMID- 8744954
TI  - Biochemical toxicology of chemical teratogenesis.
AB  - Although exposure during pregnancy to many drugs and environmental chemicals is
      known to cause in utero death of the embryo of fetus, or initiate birth defects
      (teratogenesis) in the surviving offspring, surprisingly, little is known about
      the underlying biochemical and molecular mechanisms, or the determinants of
      teratological susceptibility, particularly in humans. In vitro and in vivo
      studies based primarily on rodent models suggest that many potential embryotoxic
      xenobiotics are actually proteratogens that must be bioactivated by enzymes such
      as the cytochromes P450 and peroxidases such as prostaglandin H synthase to
      teratogenic reactive intermediary metabolites. These reactive intermediates
      generally are electrophiles or free radicals that bind covalently (irreversibly)
      to, or directly of indirectly oxidize, embryonic cellular macromolecules such as
      DNA, protein, and lipid, irreversibly altering cellular function. Target
      oxidation, known as oxidase stress, often appears to be mediated by reactive
      oxygen species (ROS) such as hydroxyl radicals. The precise nature of the
      teratologically relevant molecular targets remains to be established, as do the
      relative conditions of the various types of macromolecular lesions. Teratological
      suseptibility appears to be determined in part by a balance among pathways of
      maternal xenobiotic elimination, embryonic xenobiotic bioactivation and
      detoxification of the xenobiotic reactive intermediate, direct and indirect
      pathways for the detoxification of ROS (cytoprotection), and repair of
      macromolecular lesions. Due largely to immature or otherwise compromised
      embryonic pathways for detoxification, Cytoprotection, and repair, the embryo is
      relatively susceptible to reactive intermediates, and teratogenesis via this
      mechanism can occur from exposure to therapeutic concentrations of drugs, or
      supposedly safe concentrations of environmental chemicals. Greater insight into
      the mechanisms involved in human reactive intermediate-mediated teratogenicity,
      and the determinants of individual teratological susceptibility, will be
      necessary to reduce the unwarranted embryonic attrition from xenobiotic exposure.

PMID- 8744953
TI  - Specific interactions of chromatin with the nuclear envelope: positional
      determination within the nucleus in Drosophila melanogaster.
AB  - Specific interactions of chromatin with the nuclear envelope (NE) in early
      embryos of Drosophila melanogaster have been mapped and analyzed. Using
      fluorescence in situ hybridization, the three-dimensional positions of 42 DNA
      probes, primarily to chromosome 2L, have been mapped in nuclei of intact
      Drosophila embryos, revealing five euchromatic and two heterochromatic regions
      associated with the NE. These results predict that there are approximately 15 NE
      contacts per chromosome arm, which delimit large chromatin loops of approximately
      1-2 Mb. These NE association sites do not strictly correlate with scaffold
      attachment regions, heterochromatin, or binding sites of known chromatin
      proteins. Pairs of neighboring probes surrounding one NE association site were
      used to delimit the NE association site more precisely, suggesting that
      peripheral localization of a large stretch of chromatin is likely to result from
      NE association at a single discrete site. These NE interactions are not
      established until after telophase, by which time the nuclear envelope has
      reassembled around the chromosomes, and they are thus unlikely to be involved in
      binding of NE vesicles to chromosomes following mitosis. Analysis of positions of
      these probes also reveals that the interphase nucleus is strongly polarized in a
      Rabl configuration which, together with specific targeting to the NE or to the
      nuclear interior, results in each locus occupying a highly determined position
      within the nucleus.

PMID- 8744955
TI  - Homeostatic control of plasma calcium concentration.
AB  - Due to the importance of Ca2+ in the regulation of vital cellular and tissue
      functions, the concentration of Ca2+ in body fluids is closely guarded by an
      efficient feedback control system. This system includes Ca(2+)-transporting
      subsystems (bone, and kidney), Ca2+ sensing, possibly by a calcium-sensing
      receptor, and calcium-regulating hormones (parathyroid hormone [PTH], calcitonin
      [CT], and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]). In humans and birds, acute
      Ca2+ perturbations are handled mainly by modulation of kidney Ca2+ reabsorption
      and by bone Ca2+ flow under PTH and possibly CT regulation, respectively. Chronic
      perturbations are also handled by the more sluggish but economic regulatory
      action of 1,25(OH2)D3 on intestinal calcium absorption. Peptide hormone secretion
      is modulated by Ca2+ and several secretagogues. The hormones' signal is produced
      by interaction with their respective receptors, which evokes the cAMP and
      phospholipase C-IP3-Ca2+ signal transduction pathways. 1,25 (OH)2D3 operates
      through a cytoplasmic receptor in controlling transcription and through a
      membrane receptor that activates the Ca2+ and phospholipase C messenger system.
      The calciotropic hormones also influence processes not directly associated with
      Ca2+ regulation, such as cell differentiation, and may thus affect the calcium
      regulating subsystems also indirectly.

PMID- 8744956
TI  - Interactions of stimulus attributes, base rates, and feedback in recognition.
AB  - Continuous old-new recognition was studied in relation to 3 factors that have
      been relatively neglected in previous research-stimulus attributes, old-new base
      rates, and informative feedback following responses. Under all conditions, both
      hits and false alarms increased over trials and all measures of recognition
      depended strongly on stimulus properties, notably interitem similarity. In
      contrast to expectations based on earlier results, both hit and false-alarm
      levels proved independent of old-new base rate when tests were given without
      feedback; with feedback added, false-alarm rates tended to approach true old
      stimulus base rates with some types of stimuli, though not with words. The
      findings are compatible, in general, with current composite-memory models and
      were predicted in detail by an array-similarity model deriving from
      categorization theory.

PMID- 8744957
TI  - Intralist interference in recognition memory.
AB  - Three experiments on recognition memory were carried out to define the nature of
      intralist interference effects. Experiment 1 replicated the findings of an
      earlier study (A. I. Schulman, 1971) on what appeared to be combined study
      (input) and test (output) order effects and added information on the presence of
      speed-accuracy trade-off effects. Experiment 2 demonstrated that only test order
      was effective and that study order effects did not occur. Experiment 3
      demonstrated again that only test order was effective and also showed that the
      effect remained when response times were controlled. Attention/likelihood theory
      was fitted to the data of the final, clarified interference effect.

PMID- 8744958
TI  - Retrieval from semantic memory and its implications for Alzheimer's disease.
AB  - In 3 experiments, participants generated category exemplars (e.g., kinds of
      fruits) while a voice key and computer recorded each response latency relative to
      the onset of responding. In Experiment 1, mean response latency was faster when
      participants generated exemplars from smaller categories, suggesting that smaller
      mental search sets result in faster mean latencies. In Experiment 2, a concurrent
      secondary task increased mean response latency, suggesting that slowed mental
      processing results in slower mean latencies. In Experiment 3, the mean response
      latency of Alzheimer's participants was faster than that of elderly controls,
      which is consistent with the idea that the semantic memory impairments of
      Alzheimer's disease patients stem primarily from a reduction in available items
      (as in Experiment 1) rather than retrieval slowing (as in Experiment 2).

PMID- 8744959
TI  - Semantic effects in single-word naming.
AB  - Three experiments demonstrated that, for lower frequency words, reading aloud is
      affected not only by spelling-sound typicality but also by a semantic variable,
      imageability. Participants were slower and more error prone when naming exception
      words with abstract meanings (e.g., scarce) than when naming either abstract
      regular words (e.g., scribe) or imageable exception words (e.g., soot). It is
      proposed that semantic representations of words have the largest impact on
      translating orthography to phonology when this translation process is slow or
      noisy (i.e., for low-frequency exceptions) and that words with rich semantic
      representations (i.e., high-imageability words) are most likely to benefit from
      this interaction.

PMID- 8744960
TI  - Eye movements and lexical ambiguity resolution: effects of prior encounter and
      discourse topic.
AB  - Eye movements were monitored as participants read passages that contained 2
      occurrences of a balanced ambiguous word. In Experiment 1, local context was
      manipulated so that the meaning of the ambiguous word either remained the same or
      changed from the 1st to 2nd encounter. In Experiments 2 and 3. global context was
      manipulated by shifting the discourse topic between the 2 instances of the
      ambiguous word. Gaze durations on the 2nd instance of the ambiguous word were
      shorter when the meaning remained consistent than when the meaning changed, and
      this facilitation was impervious to changes in the discourse structure. In
      contrast, processing time in the region immediately following the target was
      longer when the word meaning changed, but only when the topic of the discourse
      remained the same throughout the passage. When the topic was shifted, this effect
      disappeared.

PMID- 8744961
TI  - Errors in short-term memory for speech: a developmental study.
AB  - In a previous study (R. Treiman & C. Danis, 1988), adults who were presented with
      lists of spoken consonant-vowel-consonant (CVC) nonsense syllables for immediate
      recall produced many errors that combined the initial consonant onset of one to
      be-remembered syllable with the vowel-consonant rime of another to-be-remembered
      syllable. These onset-rime recombination errors were more common than other types
      of recombination errors and also more common than serial position errors. These
      findings suggest that nonwords are remembered in terms of smaller phonological
      units. To replicate the previous results and to determine whether they generalize
      to children, the author tested kindergarteners, 3rd graders, 6th graders, and
      adults on lists of nonsense CVCs. Onset-rime conjunction errors were the most
      frequent type of recombination error, even among kindergarteners, suggesting that
      children code spoken syllables in terms of onset and rime units from a young age.

PMID- 8744962
TI  - Competition and segmentation in spoken-word recognition.
AB  - Spoken utterances contain few reliable cues to word boundaries, but listeners
      nonetheless experience little difficulty identifying words in continuous speech.
      The authors present data and simulations that suggest that this ability is best
      accounted for by a model of spoken-word recognition combining competition between
      alternative lexical candidates, and sensitivity to prosodic structure. In a word
      spotting experiment, stress pattern effects emerged most clearly when there were
      many competing lexical candidates for part of the input. Thus, competition
      between simultaneously active word candidates can modulate the size of prosodic
      effects, which suggests that spoken-word recognition must be sensitive both to
      prosodic structure and to the effects of competition. A version of the Shortlist
      model (D. G. Norris, 1994b) incorporating the Metrical Segmentation Strategy (A.
      Cutler & D. Norris, 1988) accurately simulates the results using a lexicon of
      more than 25,000 words.

PMID- 8744963
TI  - Repetition priming for newly formed and preexisting associations: perceptual and
      conceptual influences.
AB  - Three experiments demonstrate that association-specific repetition effects can be
      obtained for both newly formed and preexisting associations and that these
      effects are sensitive to modality of presentation. After studying a list of word
      pairs, participants were shown the original intact pairs and pairs formed by
      recombining the original pairs. In a lexical-decision task in which participants
      were asked to indicate whether both items were words, responses were faster to
      newly formed associations in the intact than in the recombined condition. This
      association-specific repetition priming effect was also observed for preexisting
      associations when a speeded relatedness judgment task was used. Both effects were
      found to be attenuated under cross-modal presentation. Finally, an explicit
      speeded recognition task revealed an associative effect that was not attenuated
      when modality was crossed for newly formed associations and was actually
      exaggerated for preexisting associations, suggesting that the repetition priming
      effects were not produced by conscious recollection. Results are discussed in
      terms of frameworks that are based either on perceptual representation systems or
      on a transfer-appropriate processing model.

PMID- 8744964
TI  - Repetition priming effects for newly formed associations are perceptually based:
      evidence from shallow encoding and format specificity.
AB  - This article is concerned with memory for newly formed associations as displayed
      on implicit and explicit tests of memory. After studying a list of word pairs,
      participants were shown the original intact pairs and pairs formed by recombining
      the original pairs. Pairs were simultaneously presented both at study and at
      test. In a lexical-decision task in which participants were asked to indicate
      whether both items were words, responses to intact pairs were faster than to
      recombined pairs. The size of this association-specific repetition effect was
      relatively unaffected by a levels-of-processing manipulation, indicating that
      conceptual processes did not likely contribute to the production of the effect.
      Furthermore, the effect was not produced when pairs were presented simultaneously
      at study but sequentially at test, thus highlighting the importance of format of
      presentation. Finally, in an explicit speeded-recognition task the size of the
      association-specific effect was largely affected by levels-of-processing
      manipulation and was revealed even under sequential test presentation suggesting
      that the associative repetition effects were not contaminated by conscious
      recollection. Together, the results show that perceptual factors are involved in
      both storage and retrieval of associative information in data-driven implicit
      tests of memory.

PMID- 8744965
TI  - Judgments of learning are affected by the kind of encoding in ways that cannot be
      attributed to the level of recall.
AB  - The authors investigated the theoretical question of whether different kinds of
      encoding can affect judgments of learning (JOLs) beyond any indirect effects
      arising from the differences those kinds of encoding produce on the likelihood of
      recall. They found that JOLs were more accurate after encoding by means of
      intentional learning than after encoding by means of incidental learning, even
      when the likelihood of recall did not differ for those kinds of encoding
      (Experiment 1), and were more accurate when intentional encoding occurred by
      generating the responses than by reading the responses (Experiment 2). An
      aggregation effect for JOLs was also discovered: Making JOLs about the likelihood
      of recall for an aggregate of items yielded less overconfidence (and even
      underconfidence) in contrast to the typical overconfidence of item-by-item JOLs.
      The overall pattern of findings suggests that JOLs are theoretically rich and are
      based on more than whatever underlies the likelihood of recall.

PMID- 8744966
TI  - Mental chronometry: beyond onset latencies in the lexical decision task.
AB  - Four experiments addressed the influence of variables on lexical decision
      performance after response initiation has occurred. In Experiment 1, participants
      made an arm movement in one direction for word trials and pressed a button with
      the other hand for nonword trials. The results indicated that word frequency not
      only modulated the speed to initiate the arm movement, but also modulated the
      acceleration and force of the movement after initiation. The results of
      Experiment 2 indicated that word frequency and stimulus degradation produced
      large and additive effects on response latency, accuracy, and the force of the
      response after initiation. In Experiments 3 and 4, participants made the same
      arbitrary speech response in a modified lexical decision task for both high- and
      low-frequency words. The results indicated that both the onset and duration of
      the speech response were modulated by word frequency. The results are viewed as
      most consistent with an enabled response model, wherein early operations can
      enable appropriate action systems before central decisions are made.

PMID- 8744967
TI  - Attentional limits in memory retrieval.
AB  - The hypothesis that episodic memory retrieval can occur in parallel with other
      cognitive processes was tested in 2 experiments. Participants memorized words and
      then performed speeded cued recall (Experiment 1) or speeded yes-no recognition
      (Experiment 2) in a dual-task situation. The psychological refractory period
      design was used: The participant was presented with a single test item at various
      stimulus onset asynchronies (SOAs; 50-1,200 ms) after a tone was presented in an
      auditory-manual 2-alternative choice reaction task. Reducing the SOA increased
      the memory task reaction times. This slowing was additive with the effect of
      variables slowing retrieval in the memory task. The results indicate that memory
      retrieval is delayed by central processes in the choice task, arguing that the
      central bottleneck responsible for dual-task interference encompasses memory
      retrieval as well as response selection.

PMID- 8744968
TI  - Belief revision in children: serial judgment in social cognition and decision
      making domains.
AB  - Belief revision in 5- to 9-year-olds was studied with an information integration
      approach. In the social task, children judged niceness of story children, having
      heard about their good and bad deeds. In the decision task, of parallel
      structure, they judged what proportion of a group of turtles' catch of starfish
      was red or gold. In both tasks, 4-5 samples were presented successively, with
      children adjusting their judgment after each. All ages took sample composition
      into account, and judgments could be described by a serial integration model
      previously supported for adults. Recency effects were found as well and were
      stronger for younger children and in the social task. Further model analysis
      showed, however, that much of this recency was short-lived and that a stable
      opinion, to which early and later informers contributed more evenly, developed
      underneath. Overall, similar processes may underlie serial belief formation
      across the age range and across domains.

PMID- 8744969
TI  - An eye movement analysis of topic-shift effect during repeated reading.
AB  - This study replicated previous reading time studies that have observed increased
      reading times for sentences introducing a new subtopic in a text, compared with
      sentences that are continuations of a subtopic. This topic-shift effect was
      obtained for the initial reading but not when the same text was reread. The
      absence of topic-shift effect was taken to suggest that readers construct a
      mental representation of the text's topic structure during the initial reading.
      The topic-shift effect was primarily due to regressive fixations, which tended to
      land in the first half of sentences. Regressions were typically launched at the
      end of sentences, with topic-shift sentences also well before the sentence end
      was reached. These findings are interpreted as evidence for the integrative
      nature of regressive fixations.

PMID- 8744970
TI  - Sequential effects in lexical decision: tests of compound-cue retrieval theory.
AB  - According to compound-cue retrieval theories, responses in lexical decision are
      determined by a passive process that matches a compound of the items in short
      term memory against all of the information in long-term memory. Because responses
      depend on other items in short-term memory in addition to the target item about
      which a lexical decision is required, compound-cue theories must predict
      sequential effects and priming effects. For example, a nonword preceding a target
      should slow responses to the target, and a prime word related to a target word
      can affect responses to the target even when another item intervenes between
      them. In this article, the results of 4 experiments are presented and sequential
      effects are shown to be in accord with compound-cue theory.

PMID- 8744971
TI  - The fate of [3H]-(-)-noradrenaline in the perfused rat liver.
AB  - 1. Hepatic removal and metabolism as well as biliary excretion of noradrenaline
      were studied. Rat livers were perfused in situ for 60 min with Krebs-Henseleit
      buffer at 37 degrees C containing 2 nM [3H]-(-)-noradrenaline. [3H]-noradrenaline
      and its [3H]-metabolites were determined in liver, venous effluent and bile. 2.
      Removal of [3H]-noradrenaline by the liver, calculated as the sum of total
      radioactivity in the liver at the end of perfusion plus total radioactivity in
      the bile formed during perfusion plus [3H]-metabolites in the venous effluent
      formed during perfusion, was 40.2 +/- 6.9 pmol g-1 h-1. This removal corresponded
      to about 25% of the amount of [3H]-noradrenaline offered to the liver. 3. A
      proportion of the [3H]-noradrenaline (86.8%) taken up by the liver was
      metabolized, 13.2% remained unmetabolized in the liver and 0.019% was excreted
      unmetabolized into the bile. The most abundant metabolites were those present in
      the [3H]-OMDA fraction (72.5%), followed by [3H]-NMN (15.8%), [3H]-DOPEG (6.1%)
      and [3H]-DOMA (5.6%). Some of these metabolites (66.6%) were recovered from the
      venous effluent, 32.7% from the liver and only 1.3% from the bile. The amount of
      [3H]-noradrenaline present in the liver at the end of the perfusion produced a
      tissue:perfusion medium ratio of 2.6. 4. Simultaneous inhibition of monoamine
      oxidase and catechol-O-methyl transferase with pargyline (75 mg kg-1, i.p., 3 h
      before) and tolcapone (1 microM), respectively, markedly reduced the formation of
      [3H]-NMN, [3H]-DOPEG and [3H]-DOMA, but did not affect the hepatic removal of
      [3H]-noradrenaline, the content of [3H]-noradrenaline in the liver, the formation
      of [3H]-OMDA or the excretion of [3H]-noradrenaline and its [3H]-metabolites into
      the bile. 5. Treatment with an uptake2 blocker, corticosterone (40 microM), did
      not change the hepatic removal and metabolism of [3H]-noradrenaline or the
      biliary excretion of [3H]-noradrenaline and its [3H]-metabolites. 6. These
      findings indicate that the perfused rat liver efficiently removed and metabolized
      [3H]-noradrenaline, both monoamine oxidase and catechol-O-methyl transferase
      being involved in the metabolism of this amine. The apparent lack of effect of
      monoamine oxidase and catechol-O-methyl transferase inhibition on the formation
      of [3H]-OMDA may be due to the presence, especially in the liver, of conjugated
      metabolites of [3H]-noradrenaline in the [3H]-OMDA fraction. These results also
      show that uptake2 does not seem to be involved in the hepatic uptake of [3H]
      noradrenaline, confirming previous findings. Finally, the results indicate that
      the rat liver perfused with Krebs-Henseleit buffer is not a suitable experimental
      model for studies on the biliary excretion of catecholamines.

PMID- 8744972
TI  - Age-related changes in contractile responses to noradrenaline in isolated blood
      vessels from rat and rabbit.
AB  - 1. Age-related changes in vascular function have been studied using rat (1, 6 and
      10 months) and rabbit (1 and 6 months) isolated aorta and rat (1, 6 and 10
      months) mesenteric perfused artery. 2. The EC50 values of noradrenaline in rat
      aorta increased with age. Similarly, contractile response to noradrenaline (10(
      6) M) and potassium (80 mM) increased with age. In rabbit aorta, contractile
      responses, both for noradrenaline and potassium, decreased with age. No changes
      were observed with age in sensitivity to noradrenaline in rat mesenteric perfused
      artery. 3. The results of the present study suggest that age-related changes may
      be different for different blood vessels. The sensitivity decrease to
      noradrenaline in rat aorta involved postreceptor mechanisms.

PMID- 8744973
TI  - Effect of age on noradrenaline responses in rat tail artery and aorta: role of
      endothelium.
AB  - 1. We have analysed the impact of ageing on the contractile responses induced by
      noradrenaline on endothelium intact and denuded aorta and tail artery rings from
      Sprague-Dawley rats. In addition, the influence of age on noradrenaline
      stimulation of phosphoinositide hydrolysis was investigated. 2. The sensitivity
      and the phosphatidylinositol hydrolysis to noradrenaline in aorta and tail artery
      were not modified by age. Intact tail artery rings showed a greater maximal
      contraction (Emax) to noradrenaline in old as compared to young animals. However,
      no Emax modification by age was observed in aorta (intact or denuded) and in
      denuded tail artery rings. 3. Removal of endothelial cells resulted in an
      increase of noradrenaline sensitivity but not the Emax in aorta from each age
      group. 4. In contrast, the absence of endothelium did not modify (young rats) or
      diminish (aged rats) the alpha 1-adrenoceptor-mediated responses in tail artery.
      5. These results seem to indicate that: (1) there is no influence of age on
      noradrenaline responses in presence of endothelium; and (2) responses in denuded
      preparations seem to indicate a differential role of endothelium on noradrenaline
      responses obtained in different vascular beds.

PMID- 8744974
TI  - Role of tachykinins as excitatory mediators of NANC contraction in the circular
      muscle of rat small intestine.
AB  - 1. The aim of this study was to assess the role of tachykinins, acting via NK1
      and NK2 receptors, in mediating nonadrenergic noncholinergic (NANC) contractions
      produced by electrical field stimulation (EFS) in the circular muscle of the rat
      small intestine. 2. In the presence of atropine (1 microM), guanethidine (3
      microM), indomethacin (10 microM), apamin (0.3 microM) and L-nitroarginine (L
      NOARG, 100 microM) and after in vitro capsaicin (10 microM for 15 min)
      pretreatment, EFS (0.25 ms pulse width, 100 V, 1-30 Hz for 5 s) produced a
      frequency-dependent NANC contraction of mucosa-free circular muscle strips from
      the rat proximal duodenum and terminal ileum. In the duodenum, the NANC
      contraction was preceded by a transient NANC relaxation. All responses to EFS
      were abolished by 1 microM tetrodotoxin. 3. The NK1 receptor selective
      antagonist, SR 140,333 (0.1 microM for 60 min) and the NK2 receptor selective
      antagonist, MEN 10,627 (0.1 microM for 60 min), both produced a partial
      inhibition of the contractile response to EFS. The co-administration of SR
      140,333 and MEN 10,627 produced a profound inhibition of the response to EFS in
      the duodenum, larger than that produced by each antagonist alone; a fraction
      (about 25% of the response at 30 Hz) of the NANC contraction of the duodenum
      persisted in the presence of the two antagonists. This residual response was
      however abolished after co-administration of the NK1 and NK2 receptor
      antagonists, GR 94,800 (1 microM) and GR 82,334 (10 microM). The co
      administration of SR 140,333 and MEN 10,627 nearly abolished the NANC contraction
      to EFS in the ileum. 4. Nifedipine (1 microM) induced a profound depression of
      the NANC contraction to EFS in both duodenal and ileal strips. A fraction of the
      response to EFS (about 25 and 5-10% of the response at 30 Hz in the duodenum and
      ileum, respectively) was nifedipine-resistant. SR 140,333 (0.1 microM) had little
      effect on the nifedipine-resistant response to EFS in the duodenum although it
      reduced by about 50% the response in the ileum. MEN 10,627 (0.1 microM) produced
      a partial inhibitory effect of the nifedipine-resistant response in both regions.
      The co-administration of SR 140,333 and MEN 10,627 nearly abolished the
      nifedipine-resistant response in the ileum while a small fraction (about 20% of
      control) of the response persisted in the duodenum.

PMID- 8744975
TI  - Muscarinic binding sites of the pig intravesical ureter.
AB  - 1. Muscarinic receptors in the pig intravesical ureter were characterized by
      binding assays in which the muscarinic receptor antagonist, (-)-[3H]
      quinuclidinyl benzylate ([3H]QNB) was used as radioligand. 2. The specific
      binding of [3H]-QNB (about 90% of the total binding, as defined with 10(-5) M
      unlabelled atropine) was dependent on protein concentration, saturable, and of
      high affinity (KD = 0.13 +/- 0.02 nM). 3. Displacement of [3H]-QNB specific
      binding by the M1-selective antagonist, pirenzepine, described a two-component
      curve, with a minor (17%) high affinity component (pKiH = 8.75), and a major
      (83%) low affinity one (pKiL = 6.34). The M3-preferential antagonists, hexa-hydro
      sila-difenidol (HHSid) and p-fluoro-HHSiD (p-F-HHSiD) delineated also two sites,
      with pKiH of 8.91 and 8.57 and pKiL of 6.94 and 7.05, respectively. However, the
      M2-selective antagonists, 11-(2-(diethyl-amino)methyl-1-piperidinylacetyl)-5,11
      dihydro-6H-p yrido-(2,3-b)- (1,4)-benzodiazepin-6-one (AF-DX 116, pKi = 6.72) and
      methoctramine (pKi = 8.34), as well as the M4-selective antagonists, tropicamide
      (pKi = 7.15) and himbacine (pKi = 8.65) fitted best to a single population of
      sites. Moreover, 4-diphenyl-acetoxy-N-methyl-piperidine methiodide (4-DAMP), a
      muscarinic antagonist that discriminates the M1 and M3 versus the M2 subtypes,
      also delineated one site (pKi = 8.36). 4. The antagonist profile clearly
      indicates the existence of an M2 population in the porcine intravesical ureter.
      In addition, the presence of a minor non-M2 population, which may be formed by a
      mixture of several muscarinic subtypes (i.e. M1, M3 and/or M4) can not be
      discounted. 5. The present work confirms the results obtained in previous
      functional studies where the stimulation of muscarinic receptors by carbachol
      evoked the contraction of the pig isolated intravesical ureter.

PMID- 8744976
TI  - Induction of insulin resistance by cholinergic blockade with atropine in the cat.
AB  - 1. Insulin sensitivity was quantified using a modified euglycaemic technique
      after hepatic cholinergic blockade with atropine and compared with that after
      surgical denervation. 2. Intraportal administration of atropine produced dose
      dependent inhibition of insulin sensitivity in glucose metabolism. ED50 of
      atropine was 0.99 mg kg-1 (1 mg = 1.5 microM) with maximum inhibition of 40.3 +/-
      11.6%. 3. Atropine (3 mg kg-1) reduced insulin sensitivity by a similar amount
      (33.6 +/- 3.4%) to that produced by hepatic surgical denervation (37.8 +/- 9.8%).
      Doses greater than 3 mg kg-1 failed to further alter the insulin resistance
      produced by surgical denervation or atropine (3 mg kg-1) administration,
      suggesting that activation of hepatic parasympathetic nerves is necessary to
      fully express the insulin effect. 4. Atropine reduced insulin sensitivity without
      changes in plasma concentrations of glucagon or insulin. The temporal response to
      insulin in this euglycaemic study was not changed after atropine administration
      or after surgical hepatic denervation. 5. It is suggested that hepatic
      parasympathetic nerves show a synergistic effect with insulin. Disease states
      that result in hepatic parasympathetic neuropathy would be expected to produce an
      insulin resistant liver. 6. The modified euglycaemic clamp method for assessing
      insulin responses was shown to be reproducible up to four times in the same
      animal and was sufficiently sensitive and quantitative to be able to generate a
      dose-response curve in each animal for atropine-induced insulin resistance.

PMID- 8744977
TI  - Increase in affinity and loss of 5-hydroxytryptamine2A-receptor reserve for 5
      hydroxytryptamine on the aorta of spontaneously hypertensive rats.
AB  - 1. The aim of this study was to determine whether the KA value and fractional
      occupancy-response relationship for 5-hydroxytryptamine (5-HT) at 5-HT2A
      receptors were altered in a rat model of genetic hypertension. Thus, the effects
      of phenoxybenzamine, an irreversible blocker at 5-HT2A-receptors, on the
      responses of the aorta from spontaneously hypertensive rats (SHRs) and
      normotensive rats to 5-HT have been examined. The two strains of normotensive
      rats used were Wistar Kyoto (WKY) rats and Wistar rats bred in Auckland (WA
      rats). 2. The sensitivity to 5-HT was increased in aortae from hypertensive rats.
      The pD2 values for 5-HT during the first challenge were 5.54 +/- 0.08 (14), 5.43
      +/- 0.05 (12) and 6.08 +/- 0.04 (12) on the aorta of WKY rats, WA rats, and SHRs,
      respectively. 3. The affinity for 5-HT was increased in hypertension.
      Phenoxybenzamine at 2 x 10(-8)M for 30 min caused nonparallel rightward shifts of
      5-HT response curves and the KA values were 16.8 x 10(-6)M, 45.6 x 10(-6)M and
      4.4 x 10(-6)M on the WKY rat, WA rat, and SHR aorta, respectively. 4. There was a
      loss of receptor reserve for 5-HT in aortae from hypertensive rats. On the WKY
      and WA rat aortae, 5-HT caused 50 and 95% maximal responses by occupying 10-20
      and 45-60%, whereas on the SHR aorta 5-HT produced 50 and 95% maximal responses
      by occupying 20-30 and 75-85% of the available 5-HT2A receptors, respectively. 5.
      The sensitivity to phenylephrine was not altered in hypertension. The mean pD2
      values for phenylephrine were 7.14 +/- 0.05 (22) and 7.11 +/- 0.06 (22) on the
      WKY rat and SHR aorta, respectively. 6. These results show that there is a
      selective increase in sensitivity to 5-HT on the aorta in a rat model of genetic
      hypertension. There is also an increase in affinity for 5-HT at the 5-HT2A
      receptors and a loss of 5-HT2A-receptor reserve for 5-HT responses on the aorta
      of SHRs.

PMID- 8744978
TI  - Influence of age on the relaxation induced by nifedipine in aorta from
      spontaneously hypertensive and Wistar Kyoto rats.
AB  - 1. Nifedipine induces relaxation in aortic segments from Wistar-Kyoto (WKY) and
      spontaneously hypertensive rats (SHR) of 5-week-, 3-month-, 6-month- and 1.5-year
      old precontracted with 50 mM K+ or 0.1 microM noradrenaline (NA). 2. In WKY rat
      segments precontracted with K+, nifedipine relaxation was reduced at 1.5 years.
      However, in SHR segments, the greatest relaxation was observed at 1.5 years. The
      relaxation elicited by nifedipine in segments from WKY of 6-month and 1.5-year
      old precontracted with NA was higher than that reached at 5-week- and 3-month
      old. However, the relaxation induced in SHR of 6-month and 1.5-year-old was only
      higher than that obtained at 5-week-old. 3. Relaxations elicited by nifedipine in
      segments from WKY precontracted with K+ were smaller than those observed in age
      matched SHR segments. 4. The endothelium positively and negatively modulates the
      relaxation to nifedipine in segments from SHR and WKY rats of different ages
      precontracted with K+, respectively. However, in segments of both strain
      precontracted with NA, endothelium removal did not alter the relaxations obtained
      at different ages. 5. These results suggest that the relaxation elicited by
      nifedipine: (1) depends on the strain, with a tendency to be greater in the
      hypertensive strain; (2) is negatively and positively modulated by endothelium in
      WKY and SHR, respectively, and (3) is influenced by age, and this influence
      depends on both the contractile agent and the strain.

PMID- 8744979
TI  - Chronic administration of oxprenolol and metoprolol attenuate sympathetic
      cardiovascular responses only in non-adrenalectomized pithed rats.
AB  - 1. Oxprenolol and metoprolol (30 mg kg-1) were injected intraperitoneally (i.p.)
      for 1 day (acute treatment) and 6 weeks (chronic treatment) to Sprague-Dawley
      rats. 2. Increases of mean blood pressure and heart rate to noradrenaline (0.1-10
      micrograms kg-1) and to electrical stimulation (0.5 msec, supramax V, 0.25-5 Hz)
      of the entire sympathetic outflow were measured in non-adrenalectomized (acute
      and chronic) and adrenalectomized (chronic) pithed rats. 3. Acute beta
      adrenoceptor antagonist administration was without effect on mean blood pressure
      and heart rate increases to noradrenaline and electrical stimulation. 4. Chronic
      administration with oxprenolol significantly diminished the stimulation-induced
      increases of mean blood pressure and heart rate in non-adrenalectomized pithed
      rats. 5. Increases in heart rate, elicited by stimulation of the entire
      sympathetic outflow in non-adrenalectomized but not in adrenalectomized pithed
      rats, were decreased by metoprolol treatment. Both treatments were without effect
      on noradrenaline responses. 6. These results indicate that chronic beta
      adrenoceptor antagonist treatment is associated with a reduction in the
      cardiovascular responses to sympathetic nerve-stimulation. However, this
      mechanism only operates when adrenomedullary adrenaline is present to facilitate
      the noradrenaline release through activation of presynaptic beta 2-adrenoceptors.

PMID- 8744980
TI  - Role of cyclic AMP and protein kinase A in K+ channel activation by calcitonin
      gene-related peptide (CGRP) in the guinea-pig ureter.
AB  - 1. The aim of this study was to assess whether agents that interfere with the
      intracellular actions of cAMP and activation of protein kinase A (PKA) prevent
      the inhibitory action of human alpha-calcitonin gene-related peptide (CGRP) in
      the guinea-pig ureter smooth muscle. The action of CGRP was compared to that of
      the K+ channel opener, cromakalim, and the adenylyl cyclase activator, forskolin,
      toward electrical field stimulation- (EFS) induced myogenic twitch contractions
      of the ureter. To further verify the role of cAMP in the action of CGRP, we also
      studied the effect of stable cAMP analogues and of the phosphodiesterase
      inhibitor, 3-isobutyl-1-methylxanthine (IBMX). 2. Maximally effective
      concentrations of CGRP (0.1 microM) or forskolin (10 microM) produced a transient
      suppression of twitches. Cromakalim (3 microM) likewise produced a prompt
      suppression of twitches that in most cases exceeded 15 min. The early suppressant
      effect of CGRP or forskolin was inhibited by 1 or 10 microM glibenclamide; about
      30% of the effect of CGRP was glibenclamide-resistant. The effect of cromakalim
      was totally suppressed by glibenclamide. 3. The inhibitory effect of CGRP was
      concentration-dependently reduced by low concentrations of barium chloride (IC50
      63 microM), which blocked with similar potency the inhibitory action of
      cromakalim (IC50 60 microM). Glibenclamide (10 nM-10 microM) concentration
      dependently inhibited the effect of CGRP and cromakalim with IC50S of 0.13 and
      0.72 microM, respectively. 4. The cAMP analogues dibutyrye-cAMP (1-3 mM), 8-(4
      chlorophenylthio)cAMP (0.3-1 mM) and Sp-cAMP monophosphothioate (0.1-0.3 mM) were
      either ineffective or poorly effective in inhibiting twitches. The cGMP analog,
      8Br-cGMP (100-300 microM) produced a slowly developing, glibenclamide (1 microM)
      resistant partial inhibition (25-30%) of twitches. 5. IBMX (1-300 microM)
      produced a concentration-dependent inhibition of twitches (EC50 16 microM). IBMX
      (100 microM) produced a large (peak 91%) and transient inhibition: glibenclamide
      (1 microM) blocked the early peak of the inhibitory action of IBMX, similar to
      the effect observed toward CGRP and forskolin.

PMID- 8744981
TI  - Phospholipase A2 myotoxins from Bothrops snake venoms.
AB  - Several myotoxins have been isolated from Bothrops snake venoms during the last
      10 years. All of them are group II basic phospholipases A2, although some lack
      enzymatic activity (i.e. Lys-49 variants). These myotoxins appear as an
      antigenically related family of proteins occurring in many, but not all, Bothrops
      venoms, bearing a close structural and antigenic relationship to toxins found in
      other crotalid venoms of the genera Agkistrodon and Trimeresurus. Myotoxins are
      quantitatively important venom components in some Bothrops species. Intramuscular
      injection of Bothrops myotoxins leads to a rapid series of drastic degenerative
      events, probably initiated at the plasma membrane level, which culminate in a
      selective skeletal muscle necrosis. This in vivo specificity contrasts with the
      ability of myotoxins to lyse many types of cells in culture. Muscle damage, as
      well as cytolysis and liposome disruption, occur in conditions where
      phospholipase A2 activity is inhibited, although enzymatic activity might enhance
      myotoxin actions. A membrane receptor for Bothrops myotoxins has not been
      identified yet. A working hypothesis on the mechanism of action is proposed.
      Current evidence suggests that these toxins interact with biological membranes
      via a molecular region distinct from their known catalytic site. The active
      region is likely to be formed by a combination of basic and hydrophobic amino
      acid residues near the C-terminus of the protein, which allow electrostatic
      interaction and bilayer penetration. These events may lead to membrane
      destabilization and loss of selective permeability to ions such as calcium, both
      of which appear to be important mediators in the process of muscle necrosis.

PMID- 8744982
TI  - A novel analgesic toxin (hannalgesin) from the venom of king cobra (Ophiophagus
      hannah).
AB  - The pharmacological effects of a purified neurotoxin from king cobra (Ophiophagus
      hannah) venom were studied. Using the hot-plate test, it is shown that this
      neurotoxin increased latency time dose-dependently when administered i.p. Similar
      analgesic action was observed when it was administered p.o. or i.c.v. The rota
      rod performance, which is a good index for neurological deficits including
      sedation, muscle relaxant and impairment of motor activity and coordination, was
      not significantly affected in the dose range of 16-32 ng/g that caused analgesia.
      The toxin did not increase the convulsion threshold in the dose range of 8-64
      ng/g in the maximal electroshock seizure tests. These results demonstrated that
      this neurotoxin produced analgesia in the dose range of 16-32 ng/g (i.p.) without
      causing any neurological or muscular deficits. It is further shown that such
      analgesic action was blocked by naloxone and L-NG-nitro-arginine methyl ester,
      suggesting the possible involvement of the opioid and nitric oxide systems,
      respectively. In view of the source of this neurotoxin (O. hannah) and its potent
      analgesic action, it is proposed that this toxin be named hannalgesin.

PMID- 8744983
TI  - Detection of cyanobacterial toxins (microcystins) in waters of northeastern
      Wisconsin by a new immunoassay technique.
AB  - The development of reliable, sensitive immunoassay techniques for detection of
      microcystins in water is becoming increasingly important. We have developed an
      enzyme-linked immunosorbent assay (ELISA) potentially able to detect microcystins
      at concentrations as low as 95 pg microcystin/ml water. The procedure uses
      antibodies extracted from the eggs of immunized chickens, eliminating the need to
      collect blood from laboratory rabbits. The antibody is able to recognize
      microcystin-LR, and -RR, and may recognize other forms of microcystin. The newly
      developed ELISA technique was utilized to measure the amount of microcystin in
      waters of northeastern Wisconsin. Of the water samples analyzed, 87% contained
      measurable amounts of microcystin (0.2-200 ng/ml). Organisms of the genus
      Microcystis were identified most frequently from microcystin-containing waters.
      The distribution of microcystin-producing cyanobacterial strains was apparently
      random throughout the sampling area.

PMID- 8744984
TI  - Immunogenicity of mastoparan B, a cationic tetradecapeptide isolated from the
      hornet (Vespa basalis) venom, and its structural requirements.
AB  - Mastoparan B (MP-B) is a cationic tetradecapeptide (LKLKSIVSWAKKVL-CONH2, mol. wt
      1611) isolated from the black-bellied hornet (Vespa basalis) venom. The small
      peptide itself was capable of inducing antibodies without prior conjugation to a
      protein carrier in rabbits and mice. The mouse antibody was found to be of IgG1
      isotype with kappa-type light chain. The peptide antigen was able to form
      insoluble complexes with the specific antibody, suggesting that MP-B possessed
      more than one epitope in its molecule. The finding that MP-B was able to bind
      with both mouse and rabbit antibodies in sandwich ELISA supports this contention.
      Synthetic MP-B analogues in which lysine at position 2, 4, 11 or 12 was replaced
      by neutral amino acids such as asparagine or leucine showed a significant
      decrease in their antibody-binding activities. Substitution of lysine at position
      4 (Lys4) caused the most marked inhibition in its binding activity. However,
      replacing tryptophan at position 9 by tyrosine caused a relatively small
      reduction in its binding activity. Replacing both Lys2,4 by asparagine or
      removing Lys-containing segments at amino or carboxyl terminus in MP-B sequence
      caused a remarkable decrease in the antibody-binding and immunogenic activities
      of the peptide. The Lys residues located at amino and carboxyl terminal segments
      of MP-B, especially Lys4, appear to play a critical role in the binding
      interaction and the immunogenicity of the peptide.

PMID- 8744985
TI  - Morphological changes induced by a generalized myotoxin (myoglobinuria-inducing
      toxin) from the venom of Pseudechis australis (king brown snake) in skeletal
      muscle and kidney of mice.
AB  - A myotoxin causing myoglobinuria was isolated from the venom of Pseudechis
      australis (PA myotoxin). Myoglobinuria was observed in mice 60 min post-injection
      (4.5 mg/kg i.m.) into calf muscles. Light microscopic observation revealed
      hypercontraction of muscle fibres with delta lesions and vacuolation. Severe
      necrosis was observed as early as 30 min. Infiltration of the muscle fibres with
      macrophages was seen by 3 hr with peak infiltration by 12-48 hr. Electron
      microscopic study showed pathological changes in skeletal muscle as early as 5
      min. Electron microscopic study showed disruption of the sarcolemma with
      dissolution and degeneration of the Z-band. Degeneration of the I-band was
      followed by degenerative changes in the A-band. Regeneration of muscle was
      evident by 3-5 days by the presence of many myotubes containing central nuclei.
      Regeneration was almost complete by 3 weeks. Contralateral soleus muscle which
      was not injected with toxin also showed degeneration followed by regeneration
      with central nuclei. Light microscopic studies of kidney showed myoglobin casts
      in both proximal and distal tubules, collecting ducts and loops of Henle. We
      conclude that this myotoxin probably acts on the Z-disc structures and also
      causes renal damage due to 'myoglobin cast nephropathy'.

PMID- 8744986
TI  - Purification and primary structure of a myotoxic lysine-49 phospholipase A2 with
      low lipolytic activity from Trimeresurus gramineus venom.
AB  - Four acidic phospholipase A2 (PLA2) isozymes named PLA2-I, II, III and IV have
      previously been isolated from Trimeresurus gramineus (green habu snake) venom and
      sequenced [Oda et al. (1991) Toxicon 29, 157; Fukagawa et al. (1992) Toxicon 30,
      1131; Fukagawa et al. (1993) Toxicon 31, 957]. They contain aspartate-49 which is
      known to bind Ca2+, essential for catalysis. In the present study, a basic PLA2
      named PLA2-V containing lysine-49 was newly isolated from the same snake venom.
      Its isoelectric point was 9.4 and considerably higher than those (c. 4.5) of PLA2
      I-IV. PLA2-V was 1.1% as active as PLA2-I toward egg-yolk emulsion but exhibited
      strong myotoxicity. The amino acid sequence of PLA2-V was determined by
      sequencing the S-carboxamidomethylated derivative and its peptide fragments
      produced by enzymatic (clostripain, chymotrypsin, Achromobacter protease I and
      Staphylococcus aureus V8 protease) cleavages. PLA2-V consists of 122 amino acid
      residues and is highly homologous (72-78%) to Lys-49 PLA2s so far isolated from
      Viperidae snake venoms but less homologous (52%) to PLA2-I. The presence of Asn
      28, which is characteristic of Lys-49 PLA2s, was confirmed.

PMID- 8744987
TI  - No role for enzymatic activity or dantrolene-sensitive Ca2+ stores in the
      muscular effects of bothropstoxin, a Lys49 phospholipase A2 myotoxin.
AB  - The role of low levels of phospholipase A2 (PLA2) activity and intracellular Ca2+
      stores in the pharmacological action of bothropstoxin (BthTX), a myotoxic Lys49
      PLA2 homologue isolated from the venom of Bothrops jararacussu, was investigated.
      We examined the muscular effects of BthTX in the mouse diaphragm and its PLA2
      activity in radiolabeled human and rat primary cultures of skeletal muscle.
      Although it is a Lys49 PLA2 homologue, BthTX had a low, but easily detectable,
      level of enzymatic activity relative to two Asp49 PLA2 enzymes from Naja naja
      kaouthia and Naja naja atra venoms, and this activity was reduced by about 85% in
      the presence of Sr2+ (4.0 mM). However, the replacement of 1.8 mM Ca2+ by 4 mM
      Sr2+ did not alter the BthTX-induced contracture and blockade of the muscle
      twitch tension. In addition, Sr2+ decreased by 50% the time required to cause 50%
      paralysis, and evoked approximately a four-fold increase in the number of
      spontaneous spikes. In isolated sarcoplasmic reticulum preparations, BthTX opened
      the intracellular Ca2+ release channel (ryanodine receptor) and lowered the
      threshold of Ca(2+)-induced Ca2+ release by a second, as yet unidentified,
      mechanism. However, in intact muscle, dantrolene, an antagonist of some forms of
      intracellular Ca2+ release, had no effect on the actions of BthTX. These findings
      do not support any role for the low levels of PLA2 activity, or dantrolene
      sensitive intracellular Ca2+ stores, in the action of BthTX. The mechanism
      whereby Sr2+ stimulates the pharmacological activity of BthTX remains to be
      clarified.

PMID- 8744988
TI  - Anxiogenic activity of centrally administered scorpion (Mesobuthus tamulus) venom
      in rats.
AB  - The anxiogenic action of intracerebroventricularly (i.c.v.) administered
      Mesobuthus tamulus venom (MTV) was investigated in rats. MTV (1, 3 and 5 g/rat,
      i.c.v.) induced a dose-related anxiogenic response which was qualitatively
      comparable to that produced by yohimbine (2 mg/kp, i.p.), an established
      anxiogenic agent. Both MTV and yohimbine reduced exploratory activity and rears,
      while increasing immobility and defaecation, in the open-field test. Likewise,
      both the drugs decreased the number of entries and time spent on the open arms of
      the elevated plus-maze, reduced social interaction and increased feed-latency in
      a novel environment. Rat brain levels of tribulin, a postulated endocoid
      indicator of anxiety, assessed in terms of endogenous monoamine oxidase (MAO) A
      and B inhibitor activity, were increased by both MTV and yohimbine. The results
      indicate that the venom has significant anxiogenic activity, which is consonant
      with some of the clinical symptoms seen after scorpion sting.

PMID- 8744989
TI  - Urinary elimination of saxitoxin after intravenous injection.
AB  - Paralytic shellfish poisoning is a serious public health concern throughout the
      world. An analytical method with diagnostic potential was used to isolate and
      measure saxitoxin, the most potent and studied paralytic shellfish poisoning
      toxin, in the urine of rats injected i.v. with sublethal doses (2 micrograms/kg)
      of saxitoxin. Urine was collected at intervals between 4 and 144 hr after
      injection. Saxitoxin was isolated from urine with an ion-exchange procedure,
      identified, and measured with a precolumn-oxidation-HPLC procedure coupled with
      fluorescence detection. The identity of oxidized saxitoxin was confirmed with
      electrospray ionization mass spectrometry. Four hours after injection,
      approximately 19% of the injected saxitoxin dose was excreted. By 24 hr,
      approximately 58% of the administered dose was excreted. Average total urinary
      excretion of administered saxitoxin was approximately 68% for the full study
      period. These results demonstrate that small quantities of unmetabolized
      saxitoxin can be detected in rat urine up to 144 hr after i.v. administration,
      and that the analytical method may have diagnostic potential for saxitoxin
      intoxication and paralytic shellfish poisoning.

PMID- 8744990
TI  - Influence of the extraction procedure on recovery of okadaic acid from
      experimentally contaminated mussels.
AB  - Hepatopancreas samples from mussels (Mytilus galloprovincialis) experimentally
      contaminated with okadaic acid were analysed with Yasumoto's mouse bioassay and
      HPLC. A likely effect of some components of the hepatopancreas on the results
      (matrix effect) was evaluated, and a possible loss of toxin during the extraction
      phase was quantified. Experiments were conducted by comparing two different
      extraction procedures. Under our experimental conditions, the results obtained
      from mouse bioassay showed no matrix effect with either procedure. A certain
      quantity of the actual amount of okadaic acid contained in the sample was found
      to be lost after the extraction, i.e. 10.2-17.0% in samples extracted with
      acetone alone and 9.8-18.5% in samples extracted with acetone and ether.

PMID- 8744991
TI  - Inhibition by clostridial neurotoxins of calcium-independent [3H]noradrenaline
      outflow from freeze-thawed synaptosomes: comparison with synaptobrevin
      hydrolysis.
AB  - Clostridial neurotoxins are known to inhibit regulated, i.e. calcium-dependent
      exocytosis. In the present study we have investigated their potential role in
      also inhibiting calcium-independent exocytosis. Synaptosomes from rat forebrain
      were preloaded with [3H]noradrenaline and permeabilized reversibly by freezing in
      Ca(2+)-free potassium glutamate containing dimethyl sulfoxide and the toxins to
      be assayed. Subsequently, outflow of radioactivity was measured in isotonic
      calcium-free potassium glutamate. The synaptic vesicle protein synaptobrevin
      2/VAMP-2 and its toxin-dependent degradation were analysed by Western blotting.
      The light chain of tetanus toxin reduced the synaptosomal outflow of
      radioactivity, whereas the activity of the heavy chain was at the detection
      limit. The respective activities of the dichain toxins from Clostridium tetani
      and C. botulinum A, B and E were enhanced by pretreatment with dithiothreitol.
      Reduced single-chain tetanus toxin was less potent than reduced dichain tetanus
      toxin. Pretreatment with ethylene diamine tetraacetic acid as an inhibitor of
      Zn(2+)-proteases abolished the actions of the tetanus toxin light chain and of
      the reduced dichain toxins. Hydrolysis of synaptobrevin-2/VAMP-2 was obtained
      with tetanus toxin light chain, reduced dichain tetanus toxin and C. botulinum B
      toxin. Its hydrolysis by single-chain tetanus toxin was less pronounced, and it
      was absent with botulinum toxins A and E. It is concluded that clostridial
      neurotoxins can not only inhibit calcium-dependent release but also affect
      calcium-independent outflow from synaptosomes. Since this is accompanied by
      selective intrasynaptosomal proteolysis of synaptobrevin, calcium-independent
      outflow may at least in part involve the vesicular release apparatus.

PMID- 8744992
TI  - Studies on the origin and distribution of palytoxin in a Caribbean coral reef.
AB  - In coral reefs of the Caribbean Sea (Colombia) palytoxin (PTX) has been detected
      in zoanthid species of the genera Palythoa and Zoanthus by assaying the delayed
      haemolysis in human erythrocytes produced by aqueous extracts, which is inhibited
      by ouabain pretreatment, and by HPLC. The toxin content of the polyps and
      colonies is highly variable and is not correlated with their reproductive cycle
      or with the amount of symbiotic algae. Sequestration of PTX has been observed in
      crustaceans (Platypodiella sp.) living in close association with Palythoa
      colonies and in polychaete worms (Hermodice carunculata) feeding on the
      zoanthids. Resistance of marine animals to the toxin may enable it to enter food
      chains.

PMID- 8744993
TI  - Bibliography of toxinology.

PMID- 8744994
TI  - Growth and development of male gymnasts, swimmers, soccer and tennis players: a
      longitudinal study.
AB  - Elite adult athletes are known to have physical and physiological characteristics
      specifically suited to their sport. However, it is not clear whether the observed
      adult differences arise because of training or whether the sport selects the
      individual with the appropriate characteristics. The purpose of this prospective
      study was to compare and contrast the physical development of young athletes (8
      19 years), and in so doing provide a possible response to this question.
      Development of anthropometric characteristics and sexual maturation were assessed
      in a group of 232 male athletes for three consecutive years. Parental heights
      were used to predict target heights. The subjects were a randomly selected group
      of young British athletes, from four sports: soccer, gymnastics, swimming and
      tennis. Using a linked longitudinal cohort study design (age cohorts 8, 10, 12,
      14 and 16 years) it was possible to estimate a consecutive 11-year development
      pattern, over the 3-year testing period. The adjusted mean (ANCOVA) height,
      accounting for age and pubertal status, of male swimmers (161.6 +/- 0.6 cm) was
      found to be significantly greater (p < 0.01) than gymnasts (150.7 +/- 0.8 cm) and
      soccer players (158.7 +/- 0.6 cm), and their adjusted mean body mass (51.3 +/-
      0.6 kg) significantly greater (p < 0.01) than the other groups. When testicular
      volumes were compared, it was found that swimmers had significantly larger
      volumes than gymnasts and tennis players from 14 to 16 years of age (p < 0.05).
      Gymnasts' growth curve of testis size was characteristic of late maturers, the
      swimmers' curve was characteristic of early maturers. As all the young athletes
      started training prior to puberty the observed late sexual maturation of gymnasts
      and early maturation of swimmers suggests some form of sports-specific selection.
      Training did not appear to have affected these young athletes' growth and
      development; rather their continued success in sport appeared to be related to
      inherited traits.

PMID- 8744995
TI  - Determinants of variability among nations in child growth.
AB  - This cross-national study aimed at understanding variability in growth among
      nations and its determinants. It examined the variability of growth among
      nations, the factors most important for explaining this variability, how these
      factors jointly determine growth, and the consistency of the patterns and
      relationships. A conceptual model was adapted from U. Jonsson. National data on
      height and weight of children, sex, ethnicity, and 15 social, economic, health,
      education, and political factors were combined from three secondary sources. A
      sequence of multiple linear regression models was used with three age groups: 1
      2, 3-5, and 6-10 years. Substantial variability in growth among nations was seen
      in comparison to that within nations. Regression models with sex, ethnicity, food
      security, maternal and child care, and health services and environment explained
      a large percentage of this variability. Institutions, politics/ideology, economic
      structure, and potential resources contributed little additionally to the models.
      Ethnic differences among nations were observed and persisted even when models
      controlled for other factors, but should not necessarily be interpreted as
      genetic differences. Determinants for height, weight, and weight adjusted for
      height were somewhat different. Adjustment for only previous growth and sex
      explained about 90% of variability in growth, supporting the assumption that
      growth patterns are generally established early in life. As policy decisions and
      programmes addressing mild-to-moderate malnutrition are increasingly considered,
      the implications of cross-national variability in growth may assume greater
      importance. Future work should examine simultaneously the effects of national,
      community, family, and individual characteristics on growth using data from
      individuals in a number of nations.

PMID- 8744996
TI  - Comparison of height acceleration curves in the Fels, Zurich, and Berkeley growth
      data.
AB  - A new type of smoothing spline designed for nonparametric estimation of growth
      acceleration curves was applied to longitudinal measures of height from the Fels,
      Zurich, and Berkeley growth studies. Landmark features of the individual
      acceleration curves were located and examined for site effects and site by sex
      interaction. The curves in each group were structurally averaged by transforming
      the age scale of each child to align the landmarks with overall means. The modal
      shapes of the structural average curves were found to be highly similar in the
      three studies, although the relative number of children who conformed to the
      modal pattern differed among the studies. Significant site by sex interactions
      were found in the timing of the landmarks associated with the pubertal growth
      spurt and with the prepubertal 'midspurt'.

PMID- 8744997
TI  - Aerobic fitness of prepubescent children.
AB  - This study was designed to enhance understanding of the assessment and
      interpretation of the aerobic fitness of prepubertal children. Written informed
      consent to participate was obtained from 70% of the children in year six of the
      15 state schools in the city of Exeter. Twenty-five per cent of the eligible
      children in each school were randomly selected from those who volunteered. The
      data reported here are those obtained from the 111 boys (11.1 SD 0.4 years) and
      53 girls (10.9 SD 0.3 years) classified as Tanner stage 1 in both pubic hair
      rating and either genitalia rating (boys) or breast rating (girls). Peak oxygen
      uptake (peak VO2) was determined using a discontinuous, incremental protocol on a
      treadmill. Only a minority of children demonstrated a levelling-off or plateau in
      VO2 despite an increase in exercise intensity. There was no evidence to suggest
      that the children who demonstrated a VO2 plateau had significantly (p < 0.05)
      higher peak VO2, peak heart rate, peak respiratory exchange ratio or peak blood
      lactate than those children who did not demonstrate a plateau in VO2. These
      findings indicate that a VO2 plateau should not be used as a requirement for
      defining a maximal exercise test with prepubertal children. Boys had a
      significantly (p < 0.01) higher peak VO2 than girls, whether expressed in 1.min-1
      (1.78 vs 1.46) or in relation to body mass (51 vs 45 ml.kg-1.min-1). The results
      compare favourably with those of similarly aged children from other countries,
      but why prepubescent boys have significantly higher (13.3%) mass-related peak VO2
      than prepubescent girls is not readily apparent. Although conventional, the
      expression of peak VO2 as per body mass ratio may not adequately partition out
      body-size differences. The influence of body mass was therefore removed using a
      linear adjustment scaling model and a log-linear model, but the boys' peak VO2
      remained significantly (p < 0.01) higher than the girls' peak VO2 with the
      difference now being 16.0% and 16.2%, respectively.

PMID- 8744999
TI  - Anthropometric comparison between high- and low-altitude Saudi Arabians.
AB  - Measurements of weight, height, mid-upper arm circumference, mid-upper arm muscle
      circumference and skinfold thickness over the triceps region were made in 437
      high-altitude residents (3150m above sea level) aged 16-60 years and 468 low
      altitude residents (500 m above sea level) aged 16-60 years in southern Saudi
      Arabia. Compared with low-altitude residents, high-altitude residents were found
      to be significantly heavier and taller, but to have nearly similar mid-upper arm
      circumference, mid-upper arm muscle circumference and triceps skinfold thickness.
      Estimates of body fat have been made from the triceps skinfold measurements. No
      significant difference in the percentage of fat was detected between high- and
      low-altitude residents. When fat mass (kg) and fat mass index (fat mass
      (kg)/height in m2) were considered, similar trends were found between highland
      and lowland men only. Highland women showed significantly higher fat mass and fat
      mass index when compared with lowland women. These differences in physique
      between highland and lowland residents of southern Saudi Arabia may be attributed
      to the effect of environmental factors, possibly the hot climate and parasitic
      infections prevalent in lowland areas, in addition to the higher physical
      activity observed in lowland women.

PMID- 8744998
TI  - Correlations among height, leg length and arm span in growing Korean children.
AB  - A cross-sectional study was performed to find out if any specific correlations
      exist among height, leg length and arm span in growing Korean children. Height,
      leg length and arm span were measured in 10,322 healthy children (4740 males and
      5582 females). Computed ratios of leg length to height, leg length to arm span
      and arm span to height for the 3rd, 25th, 50th, 75th and 97th percentiles were
      made. It was found that the ratios of leg length to height, leg length to arm
      span, and arm span to height were bigger in taller children in the same age group
      than the shorter ones in both sexes. All the ratios were bigger in older children
      in the same percentile than the younger ones in both sexes, showing that the
      growth rates of leg length and arm span were bigger than that of height in
      general. However, growth of leg length is faster in shorter children than in
      taller children until the onset of puberty, after which growth of leg length in
      taller children is faster than in shorter children. The first and most rapid
      growth of leg length is seen from birth to 2 years, the second growth spurt is
      seen during the pubertal period. An exceptional increment in leg length between
      ages from 10 to 15 is also noted in taller children. After puberty, arm span
      grows faster than height until 17 years of age in the tallest male child, and
      taller children have longer arm span than height, while arm span in the shortest
      children never exceeds height.

PMID- 8745000
TI  - Effects of thalidomide on the local Shwartzman reaction in mice and rabbits.
AB  - The Shwartzman reaction is an animal model displaying histopathological
      vasculitis phenomena. Extravasation and swelling due to increased vascular
      permeability and cellular infiltration, which are hallmarks of the Shwartzman
      reaction, were evaluated as leakage of i.v.-injected Evans Blue dye and by
      histological and immunohistological characteristics in rabbits and mice. (+/-)
      Thalidomide, (-)-thalidomide, (+)-thalidomide and dexamethasone inhibited the
      increase of vascular permeability in the local Shwartzman reaction.
      Histologically, the intensity of the Shwartzman reaction was reduced. In mice
      thrombus formation and leukocytoclastic vasculitis was inhibited by (+/-)
      thalidomide and (+)-thalidomide. ICAM-1 expression was markedly reduced after (+)
      thalidomide injection. Thalidomide and dexamethasone pretreatment reduced Mac-1
      expression on perivascular infiltrated granulocytes. The inhibitory effect of
      thalidomide on vasculitis of the Shwartzman reaction may thus be related to
      reduction of adhesion molecule expression.

PMID- 8745002
TI  - Modulation of Pseudomonas aeruginosa adherence to collagen type I and type II by
      carbohydrates.
AB  - This study was undertaken to examine if receptor recognizing saccharides may be
      involved in the adherence of Pseudomonas aeruginosa to collagen type I and type
      II. We performed an adherence inhibition assay: cells of individual P. aeruginosa
      isolates attached to immobilized collagen type I or type II in the presence of
      monosaccharides, which could serve as blockers of bacterial receptors. Bacterial
      binding to collagen type I molecules was inhibited to the highest degree by sugar
      composition D-galactose/D-mannose/N-acetylneuraminic acid (5:5:1), whereas
      attachment of P. aeruginosa to collagen type II was inhibited by composition d
      glucose/D-galactose (1:1). The same strains which were sensitive to inhibition of
      binding to collagen type II by both collagen types, were also sensitive to
      blocking by composition D-glucose/D-galactose. It suggests that saccharides play
      a role in adherence of P. aeruginosa to collagen type I and type II, and a common
      receptor for both types of collagen may be available on the surface of P.
      aeruginosa cells.

PMID- 8745001
TI  - Surface display compared to periplasmic expression of a malarial antigen in
      Salmonella typhimurium and its implications for immunogenicity.
AB  - Two different expression systems were investigated for the production of an 80
      amino acid polypeptide, M3, from the C-terminus of the Plasmodium falciparum
      blood stage antigen Pf155/RESA in an attenuated Salmonella typhimurium vaccine
      strain. Upon expression, the malarial polypeptide was targeted either to the
      periplasm as a soluble fusion protein containing two IgG-binding domains (ZZ)
      from the staphylococcal protein A or, to the bacterial surface as an insert
      within a chimeric outer membrane protein A (OmpA) derived from Escherichia coli
      and Shigella dysenteriae. Both the ZZM3 and the OmpAM3 proteins were stably
      expressed in the periplasm or on the surface of Salmonella, respectively. The ZZ
      expression system yielded 10-100 times more malarial immunogen than did the OmpA
      system. Live recombinant Salmonella expressing ZZM3 or OmpAM3 were used to
      immunize mice intraperitoneally. Both the ZZM3 and OmpAM3 genes persisted for up
      to three weeks in bacteria isolated from different lymphoid organs. Bacteria
      expressing ZZM3 induced antibodies to M3, ZZ and to the Pf155/RESA antigen
      whereas, bacteria producing OmpAM3 induced similar levels of antibodies reactive
      with M3 but not with Pf155/RESA. Both recombinants induced a memory response of
      antibodies reactive with both M3 and Pf155/RESA. The high levels of M3 produced
      by the ZZ expression system make it suitable for the expression of heterologous
      antigens in Salmonella. Nevertheless, in spite of the quantitative difference in
      M3 expression, the ZZ and OmpA constructs elicited comparable immune responses to
      M3.

PMID- 8745003
TI  - Role of tumor necrosis factor-alpha and glucocorticoid on lipopolysaccharide
      (LPS)-induced apoptosis of thymocytes.
AB  - Administration of bacterial lipopolysaccharide (LPS) into mice markedly induced
      the apoptosis of CD4+8+ thymocytes. The injection of anti-tumor necrosis factor
      (TNF)-alpha antibody or RU38486, a glucocorticoid receptor antagonist, into mice
      definitely inhibited LPS-induced apoptosis of thymocytes. Addition of the sera 1
      h after injection of LPS into in vitro cultures of thymocytes caused thymocyte
      apoptosis. It was also prevented by either anti-TNF-alpha antibody or RU38486.
      Further, recombinant TNF-alpha and hydrocortisone collaborated in induction of
      the thymocyte apoptosis in vitro. The in vivo phenomenon of LPS-induced apoptosis
      of thymocytes was reproducible by the in vitro experimental system. It was
      therefore suggested that both TNF-alpha and glucocorticoid participate and
      collaborate as effector molecules in LPS-induced apoptosis of thymocytes.

PMID- 8745004
TI  - Partial characterization of the cohemolytic factor produced by Streptococcus
      uberis and comparison with the CAMP-factor.
AB  - Exosubstances (cohemolysins) produced by Streptococcus agalactiae (CAMP-factor)
      and Streptococcus uberis (Uberis-factor) showing hemolytic synergism with beta
      lysin produced by Staphylococcus aureus were compared. Cohemolytic activity was
      evaluated in the supernatants of bacterial cultures, before and after ammonium
      sulfate precipitation. Sheep erythrocytes sensitized with beta-lysin were used as
      substrate. The assays were performed in microtiter plates and results were
      expressed as cohemolytic units/ml. Maximum cohemolytic activity was detected,
      respectively, after 8 h and 14 h of growth in Columbia broth in S. uberis and S.
      agalactiae cultures. Cohemolytic activities of both microorganisms showed
      similarities when submitted to various physical and chemical treatments. They
      were significantly decreased by heating at 60 degrees C and 100 degrees C, or in
      presence of trypsin, and were abolished in the presence of Tween 20. Activities
      were found to be stable in crude supernatants and concentrated preparations
      maintained at -20 degrees C for 3 months. Differences were related to levels of
      activity and kinetics of detection during the growth cycle. The results indicate
      the proteic nature, at least in part, of the Uberis factor. Analysis by PAGE in
      the presence or absence of SDS allowed us to correlate Uberis activity with a
      protein band with apparent molecular mass of 42 kDa, while CAMP activity was
      associated with a protein band of 27 kDa.

PMID- 8745005
TI  - The production of neuraminidase and fucosidase by Helicobacter pylori: their
      possible relationship to pathogenicity.
AB  - The pathogenicity of enterobacteria often correlates with their production of
      neuraminidase (sialidase). Forty-nine Helicobacter pylori isolates have therefore
      been examined for their production of neuraminidase and other glycosidases. All
      49 isolates produced considerable neuraminidase (median 228 IU/microg protein,
      interquartile range 121-370), pH optimum 7.5. Nine of the 49 also produced
      fucosidase (median 23 IU/microg protein, interquartile range 12-39), pH optimum
      7.0. Production of these enzymes did not correlate with bacterial Cag A
      expression or duodenal ulceration. Neutrophils exposed to neuraminidase show
      increased adherence to endothelium so the neuraminidase production by H. pylori
      could partly explain the predominant neutrophil inflammatory infiltrate seen in
      H. pylori-associated gastritis. Inhibition of this enzyme by use of neuraminidase
      inhibitors could be a useful therapeutic approach.

PMID- 8745006
TI  - Prevalence of IgG reactivity in Lyme borreliosis patients versus Borrelia garinii
      and Borrelia afzelii in a restricted area of Northern Italy.
AB  - This survey evaluates the antibody band patterns of sera taken from clinically
      defined cases of Lyme borreliosis, towards three locally isolated strains of
      Borrelia burgdorferi, belonging to the three species: Borrelia sensu stricto,
      Borrelia garinii and Borrelia afzelii, by means of Western blot. The sera were
      taken from patients resident in a limited area of Friuli Venezia Giulia (FVG)
      region. The data indicated that, besides a different feature of the band
      reactivity which correlated to the different stages of Lyme borreliosis, there
      was a preferential reactivity to the species Borrelia afzelii and Borrelia
      garinii. An immunodominant band at 51 kDa, corresponding to a protein visible in
      the electrophoretic profile of strain BL3 (B. afzelii), behaved like a marker of
      an early infection, because it was present exclusively in the sera of patient
      with ECM. The overall findings would indicate that B. afzelii and B. garinii are
      the prevalent genospecies in the FVG area, even if strains belonging to B. sensu
      stricto have been also isolated in this area. Consequently strains representative
      of these two species must be used as antigens in Western blot.

PMID- 8745007
TI  - A new improved sub-unit vaccine for plague: the basis of protection.
AB  - In this study, we have determined the limit of protection achievable by
      immunisation with sub-units of Yersinia pestis against the development of plague
      in an experimental animal model. Co-immunisation with the purified culture
      derived F1 and the recombinant V sub-units afforded a greater level of protection
      than with either sub-unit alone. The protection given by the combined sub-units
      was several orders of magnitude greater than that afforded by the whole cell
      killed (Cutter USP) vaccine and was equivalent to that achieved by vaccination
      with EV76, the live attenuated Y. pestis vaccine strain. However, the combined
      sub-unit vaccine has clear advantages over the live vaccine in terms of safety of
      use and absence of side-effects.

PMID- 8745009
TI  - Flow cytometric assay for cytotoxic activity of crude Clostridium perfringens
      enterotoxin using non-adherent cell FM3A.
AB  - The flow cytometric assay method was tested for the cytotoxic activity of
      Clostridium perfringens enterotoxin (CPE) in culture using mouse mammary
      carcinoma cell line FM3A stained with propidium iodide (PI). From the results
      obtained, FM3A cells proved to be susceptible to CPE. A reproducible dose
      response curve with FM3A was obtained between crude CPE at 13.9-109 ng/ml and
      between purified CPE at 40-400 ng/ml, respectively. These findings indicate that
      non-adherent FM3A is preferable to determine the cytotoxic activity of CPE
      because it can be used without detachment procedures with trypsinin compared with
      adherent African monkey kidney cell line (Vero cells). Furthermore, the flow
      cytometry with non-adherent cell FM3A stained with PI only proved to be a useful
      method to determine the biological activity of CPE in culture isolates.

PMID- 8745008
TI  - Prevalence of anti-R-13 antibodies in human Trypanosoma cruzi infection.
AB  - Infection with Trypanosoma cruzi develops in three phases: acute, indeterminate
      or asymptomatic, and chronic phase (with cardiac or digestive manifestations).
      Moreover, transmission may occur from infected mothers to newborn, the so-called
      congenital form. In the present study, humoral responses against T. cruzi total
      extract and against the 13 amino acid peptide named R-13 derived from the
      parasite ribosomal P protein, previously described as a possible marker of
      chronic Chagas heart disease, were determined in chagasic patients and in blood
      bank donors from endemic areas. While in sera from acute phase, only IgM anti
      T.cruzi response was observed, both IgM and IgG anti-T. cruzi antibodies were
      detected in sera from congenitally infected newborns. The percentage of positive
      response in sera from blood bank donors was relatively high in endemic regions.
      Antibodies against the R-13 peptide were present in a large proportion of cardiac
      chagasic patients but were totally lacking in patients with digestive form of
      Chagas' disease. Furthermore, anti-R-13 positive responses were detected in
      congenitally infected newborns.

PMID- 8745010
TI  - Diarrhoeal enterotoxin production by strains of Bacillus thuringiensis isolated
      from commercial Bacillus thuringiensis-based insecticides.
AB  - Strains of Bacillus cereus and B. thuringiensis were tested by the Tecra VIA kit
      for the ability to produce a diarrhoeal enterotoxin. The strains of B.
      thuringiensis were isolated from commercial B. thuringiensis-based insecticides
      (Bactimos, DiPel, Florbac, FC, Foray 48B, Novodor FC, Turex, VecTobac, XenTari).
      The production of diarrhoeal enterotoxin varied by a factor of more than 100
      among the different strains tested. B. cereus (F4433/73) produced the highest
      amount of enterotoxin and the B. thuringiensis strain isolated from DiPel the
      lowest. The products were tested for their content of diarrhoeal enterotoxin and
      all products, except MVP which does not contain viable B. thuringiensis spores,
      contained diarrhoeal enterotoxins. The results indicates an potential risk for
      gastroenteritis outbreak caused by B. thuringiensis.

PMID- 8745011
TI  - Salmonella typhimurium and Salmonella enteritidis induce gut growth and increase
      the polyamine content of the rat small intestine in vivo.
AB  - The effects of infection by Salmonella enteritidis and S. typhimurium on the
      small and large intestines, liver, spleen and mesenteric nodules of rats were
      studied in vivo. Both Salmonella serotypes persisted and proliferated in the
      gastrointestinal tract and invaded sub-epithelial tissues, mainly the ileum,
      leading to the systemic distribution of these pathogens. Coincidental with
      infection, the rate of crypt cell proliferation increased resulting in
      substantial growth of the small intestine. The extent of this and the
      accompanying accumulation of polyamines was particularly dramatic in the ileum
      where there was also some disruption of the villus epithelium. It is possible
      that these effects of the infection on the metabolism and morphology of the small
      bowel, which strongly resembled the changes induced by some plant lectins, may
      facilitate the colonisation and invasion of the gut by Salmonellae.

PMID- 8745012
TI  - Enzyme-linked immunosorbent assay (ELISA) using a glycolipid antigen for the
      serodiagnosis of melioidosis.
AB  - The serodiagnosis of melioidosis is commonly performed with tests using protein
      or polysaccharide as antigen. However, due to the low sensitivity, specificity
      and difficulty in the preparation of the antigens, more simple, precise and
      reproducible diagnostic tests were required. A purified glycolipid antigen (GL)
      which is a specific lipid component of Burkholderia pseudomallei has been used in
      an ELISA. With this antigen, specific immunoglobulin G (IgG) was detected in 49
      out of 50 melioidosis sera. IgG was also detected in 2 out of 185 (Japanese) and
      16 out of 181 (Vietnamese) control sera. Thus, the sensitivity was 98.0%, and
      specificity was 98.9% and 91.1% in the Japanese and Vietnamese sera,
      respectively. When the ELISA and indirect haemagglutination (IHA) tests were
      combined, a sensitivity of 100% and specificity of 97.8% were achieved. The
      advantages of the glycolipid antigen are ease of preparation, stability, high
      sensitivity and specificity.

PMID- 8745013
TI  - Helicobacter pylori interacts with heparin and heparin-dependent growth factors.
AB  - The pathogenic bacterium Helicobacter pylori, which causes active, chronic type B
      gastritis and peptic ulcer disease, and increases the risk for development of
      gastric cancer, could tentatively interfere with growth factors and growth factor
      receptors of importance for the gastroduodenal mucosa, e.g. heparin-binding FGFs
      (fibroblast growth factors). H. pylori binds FGF with an extremely strong
      affinity (3.8 x 10(-12)M), and also heparan sulfate and heparin with higher
      affinity (Kd 9 x 10(-9)M) than FGFs bind to heparin (10(-8) - 10(-9)M). FGF
      receptors are also dependent on heparin for their activation. Heparan sulfate
      binding proteins (HSBP) are exposed on and shed from the surface of H. pylori,
      which often are localised close to the epithelial stem cells in the
      gastroduodenal glands. H. pylori could thus efficiently interfere with growth
      factors and growth factor receptors, tentatively resulting in disturbance of the
      delicate balance that control the renewal, maintenance and repair of the
      gastroduodenal mucosa. This mode of action has previously not been considered,
      but may constitute part of its pathogenic mechanisms. Such a dynamic mode of
      action of H. pylori may explain the reason for that infected victims may either
      suffer from gastrointestinal symptoms or lack clinical evidence of disease or
      discomfort.

PMID- 8745014
TI  - Consensus: management of infections in children caused by Streptococcus
      pneumoniae with decreased susceptibility to penicillin.

PMID- 8745015
TI  - Asymptomatic carriage of intestinal Cryptosporidium in immunocompetent and
      immunodeficient children: a prospective study.
AB  - Little information is available on asymptomatic carriage of Cryptosporidium in
      immunocompetent and immunodeficient children. We prospectively studied a group of
      asymptomatic children, 78 immunocompetent and 50 immunodeficient, to document the
      incidence of asymptomatic carriage of cryptosporidiosis in such a population. We
      also investigated whether the treatment of children who carried asymptomatic
      cryptosporidiosis could help in reducing their risk of gastrointestinal symptoms
      as well as the shedding of infectious oocysts. The occurrence of multiple
      infections with common intestinal pathogens including Giardia lamblia was also
      investigated. Asymptomatic cryptosporidiosis was documented in 6.4% of
      immunocompetent and 22% of immunodeficient children. In a control symptomatic
      population Cryptosporidium was found in 4.4% of immunocompetent and 4.8% of
      immunodeficient children. Asymptomatic carriage of Cryptosporidium was documented
      in 2 human immunodeficiency virus-infected children, one of whom also carried
      Giardia asymptomatically. Treatment with spiramycin (100 mg/kg daily for 14 days)
      reduced significantly the duration of the shedding of potentially infectious
      oocysts. Finally no gastrointestinal symptoms developed in children treated for
      asymptomatic infection with Cryptosporidium, whereas children who were not
      treated developed gastrointestinal symptoms.

PMID- 8745016
TI  - Clinical and diagnostic features of osteomyelitis occurring in the first three
      months of life.
AB  - We report a retrospective study of 94 infants, ages < 4 months, who underwent
      investigation for possible osteomyelitis during a 9-year period. Of the 30 babies
      with proven osteomyelitis (radiographic changes or positive bone cultures or
      positive blood cultures plus a compatible clinical picture), 17 were preterm
      artificially ventilated babies and 4 were full term infants receiving intensive
      care. An etiologic organism was isolated from 28: methicillin-susceptible
      Staphylococcus aureus, 16; methicillin-resistant S. aureus (MRSA), 7; Escherichia
      coli, 3; and group B Streptococcus, 2. MRSA occurred exclusively in the preterm
      group. Osteomyelitis was multifocal in 40% and associated with septic arthritis
      in 47%. The long bones were frequently affected (80%) whereas the flat bones were
      often sites of clinically silent disease. Twenty-five (83.3%) of the 30 babies
      with proven osteomyelitis had focal clinical signs or evidence of disseminated
      staphylococcal disease. Only 10 were febrile. Four of 27 babies investigated
      because of positive blood cultures for S. aureus but no focal signs had
      osteomyelitis, as did only 1 of 27 babies with suspected sepsis but no focal
      signs. The sensitivity of 99mTc bone scanning was 84%, specificity 89%, positive
      predictive value 79% and negative predictive value 92%. The addition of gallium
      scanning (in 39 of the 94 infants) improved the respective figures to 90, 97, 93
      and 95% and was useful in interpreting equivocal bone scans.

PMID- 8745017
TI  - Viral etiology and epidemiology of acute lower respiratory tract infections in
      Korean children.
AB  - Viral etiologic agents of acute lower respiratory tract infections were studied
      from November, 1990, through April, 1994, in Korean children. From 712 children
      who visited or were admitted to Seoul National University Children's Hospital
      because of acute lower respiratory tract infections, 804 nasal aspirates were
      collected; viral agents were detected by virus isolation and virus antigen was
      detected by indirect immunofluorescent staining. One or more viral agents were
      identified in 369 (45.9%) cases; of which 3.3% were mixed infections. The
      pathogens identified were respiratory syncytial virus (27.2%), parainfluenza
      virus type 3 (7.8%), influenza A virus (3.9%), adenovirus (3.9%), parainfluenza
      virus type 1 (1.7%), influenza B virus (1.4%), parainfluenza virus type 2 (0.5%),
      measles virus (0.1%) and others (0.9%). The clinical patterns of viral lower
      respiratory tract included pneumonia (56.6%), bronchiolitis (35.2%), croup (6.5%)
      and tracheo-bronchitis (1.6%). Infections with respiratory syncytial virus,
      parainfluenza virus types 1 and 3 and influenza A and B virus occurred in
      epidemics, whereas adenovirus was isolated sporadically throughout the study
      period. The data expand our understanding of the epidemiology of acute viral
      lower respiratory tract infections in Korean children and may be helpful to the
      clinicians and researchers interested in the control of viral respiratory tract
      infections.

PMID- 8745018
TI  - Correlation of tuberculin induration with the number of Bacillus Calmette-Guerin
      vaccines.
AB  - In developing countries with a higher prevalence of tuberculous infection,
      usually more than one Bacillus Calmette-Guerin (BCG) vaccine is recommended.
      Revaccination can considerably alter the tuberculin skin test response and the
      diagnosis of tuberculous infection. In this study to assess the relationship
      between the number of BCG vaccinations and tuberculin skin reactions, 3548
      children (ages 6 to 12 years) from 7 elementary schools were given 5 tuberculin
      units of purified protein derivative, and results were compared taking
      vaccination status into account. Forty-seven children were excluded from the
      study. Mean purified protein derivative induration size at 72 hours was 3.2 +/-
      3.9 mm with no BCG scar (n = 1518), 6.3 +/- 7.8 mm with 1 scar (n = 1513), 10.7
      +/- 6.2 mm with 2 scars (n = 433) and 14.8 +/- 4.3 mm with 3 scars (n = 37). In
      children with no scar the 90th percentile values of the size of the purified
      protein derivative induration were 10 mm. The 90th percentile values of children
      with one, two and three scars were 15, 17.5 and 20 mm, respectively. We suggest
      that tuberculin skin test responses be evaluated with regard to the number of
      previous BCG vaccinations.

PMID- 8745019
TI  - Genotypic analysis of a cluster of systemic Candida albicans infections in a
      neonatal intensive care unit.
AB  - Five very low birth weight infants developed systemic Candida albicans infection
      during a 6-week period in an urban neonatal intensive care unit. In an effort to
      assess whether a common source outbreak was present, the genomic DNA of the
      clinical isolates was compared by EcoRI and XbaI restriction fragment analysis
      and Southern blot hybridization with 27A, a species-specific, transposon-like
      probe. Although the restriction fragment analysis suggested strong similarities
      among the isolates, the hybridization patterns demonstrated that all strains were
      genotypically distinct. The parallel use of at least two restriction enzymes was
      important for differentiating the isolates. Rapid genotypic analysis of clinical
      isolates from a cluster of C. albicans infections permits determination of
      whether a common source is probable, facilitates epidemiologic decisions and may
      reduce infection control measures and attendant costs.

PMID- 8745020
TI  - Randomized trial of the efficacy of trimethoprim-sulfamethoxazole and prednisone
      in preventing post-tympanostomy tube morbidity.
AB  - This study was designed to determine whether treatment with prednisone and
      trimethoprim-sulfamethoxazole would reduce first year post-operative morbidity in
      children with chronic otitis media with effusion undergoing tympanostomy tube
      insertion (intubation). Eighty children ages 6 months to 8 years were enrolled at
      intubation and randomized from age strata to receive active drugs or placebos for
      14 days after surgery. They were examined with pneumatic otoscopy and
      tympanometry preoperatively and at 3 weeks and 3, 6, 9 and 12 months after
      surgery. Active drug treatment significantly reduced tube obstruction or
      extrusion in the first 3 postoperative months compared with placebos (4% vs. 17%,
      P = .01). However, rates of repeat intubation, otorrhea and recurrence of otitis
      media did not differ significantly in the two groups. Children with chronic
      otitis media with effusion treated with intubation may benefit from a 2-week
      course of prednisone and trimethoprim-sulfamethoxazole at the time of surgery.
      However, there is no apparent long term benefit of this treatment.

PMID- 8745021
TI  - Increasing incidence of penicillin- and ampicillin-resistant middle ear
      pathogens.
AB  - During a 13-month period ending in January, 1995, we obtained 159 samples of
      middle ear exudate through tympanocentesis (n = 155) or acute spontaneous
      otorrhea (n = 4) from 151 children enrolled in therapeutic trials of acute otitis
      media in a pediatric practice in Northern Virginia. Their ages ranged from < 1 to
      > 6 years of age (mean, 35 months; median, 22 months). Precise diagnostic
      criteria for acute otitis media always included bulging outward of all or part of
      the eardrum, opacification of the eardrum regardless of color and impaired
      mobility to positive and negative pressure via the pneumatic otoscope. Bacterial
      pathogens were isolated from middle ear fluid in 95% of these children:
      Streptococcus pneumoniae was recovered from 61 (37%); Haemophilus influenzae from
      45 (27%); Moraxella catarrhalis from 41 (25%); Group A streptococcus from 6 (4%);
      Staphylococcus aureus from 4 (2%); and no growth or microbes of uncertain
      significance from 8 (5%). Six of the patients had mixed bacterial cultures; 2 of
      the 6 had at least one ampicillin-resistant bacteria, and a third had 2
      ampicillin-resistant bacteria. Eight patients who failed to improve with
      antimicrobial treatment had a second tympanocentesis performed or developed
      spontaneous drainage; on that follow-up culture 3 of 8 cultures had different
      microorganisms; and 5 of the 8 bacterial specimens were resistant to ampicillin
      or penicillin. Twenty-one percent of the S. pneumoniae strains recovered from the
      middle ear were resistant to penicillin. Sixty-two percent of the H. influenzae
      and 98% of the M. catarrhalis isolates were resistant to ampicillin. Overall
      bacteria resistant to penicillin or ampicillin were recovered in 54% of middle
      ear fluid from 46 patients who had received a beta-lactam antibiotic in the
      preceding month as well as in 57% of middle ear fluids from 105 patients who had
      not. The empiric use of amoxicillin for treatment of acute otitis media should be
      reexamined in our community particularly in those who appear ill, have a high
      fever or have severe unremitting otalgia.

PMID- 8745022
TI  - Infective endocarditis in children: clinical analyses and evaluation of two
      diagnostic criteria.
AB  - A new diagnostic schema for infective endocarditis (IE), the Duke criteria, has
      been compared with the previously published criteria of von Reyn in adult
      patients. This study was designed to analyze the clinical characteristics of a
      group of pediatric patients with IE and to compare the diagnostic efficiency of
      both sets of criteria. We reviewed retrospectively the clinical records of 38
      patients, 22 with predisposing heart disease (Subgroup A) and 16 with no known
      cardiologic abnormality (Subgroup B). Ventricular septal defect was the most
      frequent preexisting heart disease (31.8%) and central venous catheters were the
      most frequent predisposing factor (68.7%). Comparison of the clinical features
      between subgroups (A vs. B) showed differences only for the presence of a new
      regurgitant murmur (9% vs. 44%, P < 0.05) and a hemoglobin value < or = 10 g/dl
      (50% vs. 94%, P < 0.05). The most frequent microorganisms isolated were viridans
      streptococci (36%) in Subgroup A and Staphylococcus aureus (50%) in Subgroup B.
      Of the 6 pathologically confirmed cases all would have been classified as
      clinically definite by the Duke criteria, as compared with 2 of 6 being defined
      as probable and one being rejected by von Reyn criteria. Of the 32 cases
      clinically defined 19 (59%) were classified as definite by the Duke criteria, and
      11 (34%) were probable by the von Reyn criteria (difference 25%, P < 0.01).
      Although no case of IE was rejected by Duke criteria, 8 (25%) were rejected by
      von Reyn criteria (difference 25%, P < 0.01), with all 8 classified as possible
      by Duke criteria. We conclude that the Duke criteria were superior to the von
      Reyn criteria for the diagnosis of pediatric IE, including more cases as definite
      and significantly fewer cases as rejected.

PMID- 8745023
TI  - Plasma bactericidal/permeability-increasing protein concentrations in critically
      ill children with the sepsis syndrome.
AB  - Bactericidal/permeability-increasing protein (BPI) is a neutrophil azurophilic
      granule component that is bactericidal towards Gram-negative bacteria and
      inhibits lipopolysaccharide-mediated inflammatory responses. We conducted a
      prospective study to measure plasma BPI concentrations in 36 critically ill
      children with and without the sepsis syndrome. Plasma BPI concentrations ranged
      from 0.5 to 452 ng/ml. Patients with the sepsis syndrome had higher median plasma
      BPI concentrations than critically ill controls (5.1 vs. 1.8 ng/ml, P = 0.006).
      Patients with organ system failure had higher median plasma BPI concentrations
      than those with no organ system failure (4.5 vs. 1.3 ng/ml, P = 0.001). Plasma
      BPI concentrations were positively associated with pediatric risk of mortality
      score (P = 0.03, rs = 0.4). These data provide the first clinical insights
      regarding the role of endogenous BPI production in critically ill children and
      suggest that BPI may play an important role in host defenses.

PMID- 8745024
TI  - Use of eyepatches in phototherapy: effects on conjunctival bacterial pathogens
      and conjunctivitis.
AB  - We conducted a randomized controlled trial to determine the effects of eye
      occlusion on the risk of eye infection in full term newborn infants receiving
      phototherapy. Among 102 infants whose eyes were occluded with eyepatches,
      pathogens were isolated from 50 eyes of 33 infants. The positive isolation rate
      was significantly higher than that of a group of control infants (n = 101) whose
      eyes were protected by a headbox made of light-proof plastics. Among the latter
      group pathogens were detected in 22 eyes of 14 infants. In addition significantly
      more infants in the eyepatches group had purulent eye discharge (23 of 102 vs. 9
      of 101, P = 0.013) and clinical conjunctivitis (13 of 102 vs. 2 of 101, P =
      0.004) than the controls. Proper eye care is imperative when eyepatches are used
      on infants receiving phototherapy, and alternative methods of eye protection
      should be considered.

PMID- 8745025
TI  - Fatal enterovirus type 71 infection: rapid detection and diagnostic pitfalls.

PMID- 8745026
TI  - Lack of bacteremia in children undergoing myringotomy and tympanostomy tube
      placement.

PMID- 8745027
TI  - Hypereosinophilia in disseminated cryptococcal disease.

PMID- 8745028
TI  - Successful outpatient treatment of Trichosporon beigelii peritonitis with oral
      fluconazole.

PMID- 8745029
TI  - Pneumococcal parotitis in a human immunodeficiency virus-infected child.

PMID- 8745030
TI  - Brain edema: an underdiagnosed complication of Shigella infection.

PMID- 8745031
TI  - Fatal ceftriaxone-induced hemolysis in a child with acquired immunodeficiency
      syndrome.

PMID- 8745032
TI  - Life-threatening gastrointestinal bleeding caused by aphthous ulcers in a patient
      with perinatal acquired immunodeficiency syndrome.

PMID- 8745033
TI  - Posterior neck mass in a four-year-old boy.

PMID- 8745034
TI  - Accuracy of leukocyte indices and C-reactive protein for diagnosis of neonatal
      infection.

PMID- 8745035
TI  - Repeated lumbar punctures.

PMID- 8745036
TI  - Safety and efficacy of diphtheria-tetanus toxoids-pertussis-Haemophilus
      influenzae type b combination vaccine.

PMID- 8745037
TI  - Screening visitors for tuberculosis.

PMID- 8745038
TI  - Hepatitis B immunization of adolescents.

PMID- 8745039
TI  - Failure of posttrial administration of vasopressin analogue (DDAVP) to influence
      memory in healthy, young, male volunteers.
AB  - The effects of intranasal treatment with DDAVP on healthy, male volunteers was
      assessed. Subjects were asked to learn prose passages and then were given either
      60 micrograms of DDAVP or saline in a double-blind procedure. Subjects were then
      asked to recall the passages after a 24-h delay. Treatment had no effect on
      recall of passages. This suggests that treatment with vasopressin affects
      acquisition rather than consolidation of newly learned information.

PMID- 8745040
TI  - Altered alertness of vasopressin-secreting transgenic mice.
AB  - We evaluated behavior and cognitive performance in a line of transgenic mice that
      overexpress the rat gene for vasopressin. Open field testing revealed greatest
      habituation in homozygous mice. Passive avoidance performance indicated equal
      learning and memory ability of transgenic compared to normal mice. Drinking
      behavior following exposure to 10% sucrose solution suggested diminished
      neophobia in homozygous mice. These observations are consistent with enhanced
      attention and alertness in the transgenic animals and support prior observations
      on the effects of vasopressin on behavior and cognitive function.

PMID- 8745041
TI  - Hydrolysis of cyclosporin A: identification of 1,11 seco-cyclosporin A and 4,5
      seco-isocyclosporin A by FAB-MS/MS.
AB  - We have previously reported that treatment of CsA with aqueous HCI gives rise to
      the formation of a number of water-soluble compounds. Two of these were
      identified from their FAB-MS/MS spectra as open-chain nona- and decapeptides. We
      describe here the identification of two other main compounds deriving from the
      same treatment. Identification was rendered possible from the comparison of their
      FAB-MS/MS spectra with those of methyl and acetyl derivatives. The two compounds
      are water-soluble, open-chain undecapeptides corresponding to 1.11 seco-CsA and
      of 4.5 seco-isoCsA, respectively.

PMID- 8745042
TI  - Pharmacokinetic, metabolic, and antidiarrheal properties of (D and L)
      heptapeptides of sorbin in rodent.
AB  - The C-terminal heptapeptide-amide (C7-sorbin) is the minimal biologically active
      fragment of sorbin inducing an increase in intestinal hydroelectrolytic
      absorption. An analogue (D7-sorbin), characterized by the replacement of the
      ultimate C-terminal amino acid L-alanine-amide by D-alanine-amide, was
      synthetized. For pharmacokinetic studies, D7-sorbin and C7-sorbin were tritium
      labeled. After IV injection, clearances were 10.6 and 30.2 ml-1 for D7-sorbin and
      C7-sorbin, respectively, and MRT were 34 and 18 min. After SC administration,
      Cmax attained 0.41% and 0.12% of the dose/ml, respectively. The IP route showed a
      45-min delay before Cmax and a 100% bioavailability for both peptides. D7-sorbin
      was principally excreted in urine, as shown by balance study, and in part in
      intact form, as controlled by mass spectrometry. D7-sorbin induced a significant
      decrease of the VIP-induced ileal secretion, previously observed with C7-sorbin.
      The change of L-Ala to D-Ala increased the stability of the synthetic C-terminal
      peptide of sorbin whereas its biological activity, bioavailability, and route of
      elimination were unchanged.

PMID- 8745043
TI  - Isolation of a renin-like enzyme from the leech Theromyzon tessulatum.
AB  - This article reports the purification of a renin-like enzyme (an aspartyl
      protease) from head parts of the leech Theromyzon tessulatum. After four steps of
      purification including gel permeation and anion exchange chromatographies
      followed by reversed-phase HPLC, this enzyme was purified to homogeneity. The
      renin-like enzyme (of 32 kDa) hydrolyses at neutral pH and at 37 degrees C, the
      Leu10-Leu11 bond of synthetic porcine angiotensinogen tetradecapeptide yielding
      the angiotensin I and the Leu11-Val12-Tyr13-Ser14 peptide as products, with a
      specific activity of 1.35 pmol AI/min/mg (Km 22 microM; Kcat 2.7). The hydrolysis
      of angiotensinogen is inhibitable at 90% by pepstatin A (IC50 = 4.6 microM),
      consistent with a renin activity. This is the first biochemical evidence of renin
      like enzyme in invertebrates.

PMID- 8745044
TI  - A bradykinin-potentiating peptide (peptide K12) isolated from the venom of
      Egyptian scorpion Buthus occitanus.
AB  - A nontoxic peptide with bradykinin-potentiating activity was isolated from the
      dialyzed venom of the scorpion Buthus occitanus by reverse-phase high performance
      liquid chromatography (RP-HPLC). The pharmacological activity of the peptide was
      bioassayed by its ability to potentiate added bradykinin (BK) on the isolated
      guinea pig ileum as well as the isolated rat uterus for contraction. Moreover,
      the peptide potentiates in vivo the depressor effect of BK on arterial blood
      pressure in the normotensive anesthetized rat. Chemical characterization of the
      peptide was also performed. The amino acid composition of the peptide showed 21
      amino acid residues per molecule including three proline residues. The amino acid
      sequence of the purified peptide was confirmed by mass spectrometry. Either N- or
      C-terminal ends were free. The sequence does not show a homology with bradykinin
      potentiating peptides isolated from either scorpion or snake venoms. Furthermore,
      we did not find a significant sequence homology between the sequence of the
      isolated peptide and any of proteins or peptides in GenPro or NBRF data banks.
      The peptide also inhibited angiotensin-converting enzyme (ACE), and could not
      serve as substrate for the enzyme. It could be concluded that the mechanism of
      bradykinin-potentiating peptide (BPP) activity may be due to ACE inhibition.

PMID- 8745045
TI  - Angiotensin and bradykinin metabolism by peptidases identified in cultured human
      skeletal muscle myocytes and fibroblasts.
AB  - Angiotensin (ANG) and kinin metabolizing enzymes, angiotensin-converting enzyme
      (ACE; EC 3.4.15.1), neutral endopeptidase-24.11 (NEP-24.11; EC 3.4.24.11), and
      aminopeptidase M (AmM; EC 3.4.11.2), have recently been identified in a purified
      skeletal muscle glycoprotein fraction. We have analyzed the cellular localization
      of these enzymes. In cultured human skeletal muscle adult myoblasts, myotubes,
      and fibroblasts, kinins and angiotensins were metabolized by NEP-24.11 and AmM
      but not by ACE. NEP-24.11 degraded ANG II, ANG III. and bradykinin (BK) and
      converted ANG I to the active metabolite ANG(1-7). ANG III was converted to the
      novel ANG IV metabolite [des-Arg1]ANG III by AmM. These data suggest that, due to
      their abundance in the body, skeletal muscle myocytes and fibroblasts may play a
      major role in modulation of the systemic and local effects of angiotensins and
      kinins. This role could be particularly important in individuals receiving
      treatment with ACE inhibitors.

PMID- 8745046
TI  - Amino acid sequence of the minor isomorph of the crustacean hyperglycemic hormone
      (CHH-II) of the Mexican crayfish Procambarus bouvieri (Ortmann): presence of a D
      amino acid.
AB  - The primary structure of the neurohormone crustacean hyperglycemic hormone (CHH
      II) was determined by means of enzymatic digestions, manual Edman degradation,
      and mass spectrometry. CHH-II is a 72 residue peptide (molecular mass 8388 Da),
      with six cysteines forming three disulfide bridges that connect residues 7-43, 23
      39, and 26-52. The peptide has blocked N- and C-termini, and lacks tryptophan,
      histidine, and methionine. The CHH-I and CHH-II of Procambarus bouvieri have
      identical sequences and elicit levels of hyperglycemia that are not
      distinguishable. The difference between the two isomorphs consists in a
      posttranslational modification of a L-Phe in CHH-I to a D-Phe in CHH-II at the
      third position from the N-terminus.

PMID- 8745047
TI  - Purification and structural characterization of insulin from a caecilian,
      Typhlonectes natans (Amphibia: Gymnophiona).
AB  - Despite the important position of amphibia in phylogeny, efforts at the
      structural characterization of amphibian neurohormonal peptides have largely been
      confined to the Anurans (frogs and toads). Insulin was purified from an extract
      of the pancreas of the caecilian, Typhlonectes natans. The primary structure of
      the peptide was established as: [formula: see text] This amino acid sequence
      contains several unusual substitutions (Gln-->Lys at A5, His-->Leu at A8, Gln-
      >Glu at A15, and Gly -->Ala at B20) that are not present in other amphibian
      insulins. The structure of insulin appears to be less well conserved among the
      different orders of amphibia, compared with reptiles and birds.

PMID- 8745049
TI  - Distribution of enteric neural peptide YY in the dog gastrointestinal tract.
AB  - Various regions of the dog gastrointestinal tract were investigated for the
      distribution of peptide YY (PYY) neurons using immunocytochemistry and
      radioimmunoassay. PYY neurons that encircled non-PYY-immunoreactive neurons were
      mainly observed in the myenteric plexus from the stomach to the colon. There was
      more PYY-like immunoreactivity in the muscle layer of the stomach and ileum than
      in the other intestines. The results of high performance liquid chromatography
      revealed that neural PYY-immunoreactive substance is identical to authentic PYY.
      PYY was not localized in the cholinergic neurons. These results indicate that
      PYY, as a neuropeptide, is involved in the regulation of gastrointestinal
      function.

PMID- 8745048
TI  - Receptor binding profiles of NPY analogues and fragments in different tissues and
      cell lines.
AB  - To investigate receptor selectivity and possible species selectivity of a number
      of NPY analogues and fragments, receptor binding studies were performed using
      cell lines and membranes of several species. NPY displays 4-25-fold higher
      affinity for the Y2 receptor than for the Y1 receptor. The affinity of
      [Leu31,Pro34]NPY is 7-60-fold higher for the Y1 receptor when compared with the
      Y2 subtype. Species selectivity within the Y2 receptors is demonstrated by PYY(3
      36), NPY(2-36), NPY(22-36), and NPY(26-36). It is shown that NPY(22-36) is
      species selective for the human Y2 subtype (K1 of 0.3 nM) compared with the
      rabbit and rat Y2 receptor (K1 of 2 and 10 nM, respectively). PYY(3-36) displays
      highest affinity for the human and rabbit Y2 subtype (K1 of 0.03 and 0.17 nM).
      The screening of NPY analogues and fragments revealed that highest affinity for
      the human Y2 receptor is shown by NPY(2-36) and PYY(3-36). In addition, PYY(3-36)
      and NPY(2-36) are not only subtype selective, but also species selective.

PMID- 8745050
TI  - Effects of peptide YY and its analogues on chloride ion secretion in fed and
      fasted rat jejunum.
AB  - The aim of our study was to determine whether a meal modifies the antisecretory
      response induced by PYY and the structural requirements to elicit antisecretory
      effects of analogue PYY(22-36) for potential antidiarrhea therapy. The variations
      in short-circuit current (Isc) due to the modification of ionic transport across
      the rat intestine were assessed in vitro, using Ussing chambers. In fasted rats,
      PYY induced a dose- and time-dependent reduction in Isc, with a sensitivity
      threshold at 5 x 10(-11) M (delta Isc -2 +/- 0.5 microA/cm2). The reduction was
      maximal at 10(-7) M (Isc -23 +/- 2 microA/cm2), and the concentration producing
      half-maximal inhibition was 10(-9) M. At 10(-7) M, reduction of 1sc by PYY
      reached 90% of response to 5 x 10(-5) M bumetanide. The PYY effect was partly
      reversed by 10(-5) M forskolin (Isc + 13.43 +/- 2.91 microA/h.cm2, p < 0.05) or
      10(-5) M dibutyryl adenosine 3',5' cyclic monophosphate (Isc + 12 +/- 1.69
      microA/cm2, p < 0.05). Naloxone and tetrodotoxin did not alter the effect of PYY.
      In addition, PYY and its analogue P915 reduced net chloride ion secretion to 2.85
      and 2.29 microEq/cm2 (p < 0.05), respectively. The antisecretory effect of PYY
      was accompanied by dose- and time-dependent desensitization when jejunum was
      prestimulated by a lower dose of peptide. The antisecretory potencies exhibited
      by PYY analogues required both a C-terminal fragment (22-36) and an aromatic
      amino acid residue (Trp or Phe) at position 27. At 10(-7) M the biological
      activity of PYY was lower in fed than fasted rats (p < 0.001). Our results
      confirm the antisecretory effect of PYY, but show that the fed period is
      accompanied by desensitization, similar to the transient desensitization observed
      in the fasted period with cumulative doses. This suggests that PYY may act as a
      physiological mediator that reduces intestinal secretion.

PMID- 8745051
TI  - Hypotensive effects of [D-Tyr27,36, D-Thr32]Neuropeptide Y (27-36).
AB  - An analogue of the 10 C-terminal amino acids of neuropeptide Y (NPY) containing
      three D-isomeric substitutions (27-36-D) has been synthesized and its
      cardiovascular activity studied in Sprague-Dawley (SD) and spontaneously
      hypertensive (SHR) rats. Intravenous administration of 1000 nmol/kg 27-36-D
      decreases MAP in SHR (-59.9 +/- 5.0 mmHg) and SD rats (-44.4 +/- 4.7 mmHg). The
      hypotension produced by 1000 nmol/kg 27-36-D diminished by 71.2% following
      pretreatment with the histamine receptor antagonist diphenhydramine, although
      histamine depletion with compound 48/80 does not significantly alter this
      hypotension. These data suggest that NPY (27-36)-D produces a profound and
      sustained hypotension in two strains of rat which is partially attributable to
      activity at histamine receptors.

PMID- 8745052
TI  - Psychostimulant-like effect of central microinjection of neurotensin on brain
      stimulation reward.
AB  - The curve shift method and the brain stimulation reward paradigm were used to
      dissociate reward and performance changes and determine whether unilateral ICV
      microinjection of neurotensin (3, 10, and 30 micrograms/10 microliters) produces
      neuroleptic- or psychostimulant-like effect on a dopamine-dependent behavior. At
      the highest dose tested, neurotensin potentiated brain stimulation reward,
      producing a significant time-dependent decrease in frequency threshold.
      Neurotensin also suppressed maximal rate of responding at every dose tested,
      suggesting that it was more effective at attenuating performance capability.
      These results suggest that a centrally acting neurotensin receptor agonist may
      specifically stimulate dopamine-dependent behaviors, producing psychostimulant
      like effect that can be attenuated or masked by a suppression of performance
      capability.

PMID- 8745053
TI  - Synaptic relations of neurotensinergic neurons in the dorsal raphe nucleus.
AB  - The ultrastructure and synaptic relations of neurotensinergic neurons in the rat
      dorsal raphe nucleus (DRN) were examined. The neurotensin-like immunoreactive (NT
      L1) neurons in the DRN were fusiform or spherical. The NT-LI perikarya could only
      be detected in colchicine-treated animals whereas the immunoreactive axon
      terminals could only be found in the animals not treated with colchicine.
      Although many NT-LI dendrites received synapses from nonimmunoreactive axon
      terminals, the NT-LI perikarya received few synapses. NT-LI axon terminals also
      made synapses on nonimmunoreactive dendrites. Occasionally, synapses were found
      between the NT-LI axon terminals and NT-LI dendrites in the cases in which the
      animals were not treated with colchicine.

PMID- 8745054
TI  - Effect of CCK-8 on myoelectrical activity of the gastrointestinal tract in the
      conscious miniature pig.
AB  - In conscious miniature pigs, with implanted electrodes in the wall of the antrum
      pylori, duodenum, jejunum, and ileum, the influence of IV infusions of CCK-8
      (17.5 and 175 pM/kg/min) on gastrointestinal myoelectrical activity was measured.
      Although both doses under study induced a decrease in antral spike activity. only
      the higher dose resulted in an overall decrease in integrated myoelectrical
      activity. In the ileum both doses augmented spiking activity during the infusion,
      but inhibited electrical activity after the end of the infusion. No response was
      observed in the duodenum and jejunum. The experiments demonstrate the overall
      inhibitory effect of CCK-8 on antral electrical activity and its stimulatory
      influence on ileal smooth muscle.

PMID- 8745055
TI  - Cytokines suppress the shear stress-stimulated release of vasoactive peptides
      from human endothelial cells.
AB  - Endothelial cells from human umbilical vein perfused at 0.5 ml/min released
      vasopressin, endothelin, and substance P. Upon perfusion of the cells at 3.0
      ml/min, the release of endothelin and vasopressin was significantly increased
      whereas the release of substance P was significantly decreased. Endothelial cells
      precultured for 24 h with interleukin-1 (IL-1) and interferon-gamma (IFN-gamma)
      released more endothelin and less substance P at low flow and there was no
      further increase in release at high flow rate. These results suggest that
      cytokines suppress the normal responses of endothelial cells to increased fluid
      shear stress.

PMID- 8745056
TI  - Pressor and tachycardic responses to intravenous substance P in anesthetized
      rats.
AB  - Intravenous injection of 3-33 nmol/kg of substance P (SP) caused pressor and
      tachycardic responses in anesthetized rats. The responses were not blocked by a
      ganglion nicotinic receptor antagonist or by pithing. Pretreatment with reserpine
      blocked both responses. beta-Adrenoceptor blockade attenuated only the
      tachycardic response, and alpha-adrenoceptor blockade attenuated only the pressor
      response. These findings indicated that the effects of SP to increase blood
      pressure and heart rate are due to sympathetic ganglion stimulation. Studies with
      adrenalectomized rats showed that stimulation of the adrenals by SP contributes
      to both responses but makes a greater contribution to the tachycardic response.
      These observations raise the possibility that the tachykinin innervation of
      sympathetic ganglia and the adrenal medulla may be involved in the local
      regulation of blood pressure and heart rate.

PMID- 8745057
TI  - Substance P induces degranulation of mast cells and leukocyte adhesion to venular
      endothelium.
AB  - Substance P (SP), one of the established neurotransmitters, evokes an
      immunoinflammatory response involving leukocyte adhesion to venular endothelium
      and the degranulation of mast cells. The pathogenetic relationship between these
      responses, however, remains unresolved. In this study, we propose to examine the
      changes associated with the activation of mast cells, as well as leukocyte
      adhesion to venular endothelium by in vivo observation of the rat mesentery. The
      use of an in vitro assay for intracellular Ca2+ mobilization and the
      degranulation of mast cells demonstrated the significant upper shift of
      concentration response to SP (10(-4)-10(-5) M). In vivo experiments on the
      mesenteric microcirculation also showed that SP induced a significant increase in
      the number of degranulated mast cells as well as in the number of leukocytes
      adherent to the venular wall. Tranilast, a mast cell stabilizer, as well as SP
      antagonist (CP-96,345) significantly attenuated the extent of mast cell
      degranulation and leukocyte adhesion elicited by SP. Although an
      immunoneutralization against CD18 by WT-3 significantly attenuated the leukocyte
      adhesion, it had no influence on the mast cell degranulation after SP
      superfusion. These separate in vivo observations show that SP induces leukocyte
      adhesion to the venular endothelium, possibly through the degranulation of mast
      cells.

PMID- 8745058
TI  - Effect of phenylephrine and prazosin on the somatostatinergic system in the rat
      frontoparietal cortex.
AB  - Somatostatin (SS) and noradrenaline (NA) are distributed in the rat cerebral
      cortex, and seizure activity is one of the aspects of behavior affected by both
      neurotransmitters. Due to the possible interaction between both neurotransmitter
      systems, we studied whether phenylphrine, an alpha 1-adrenoceptor agonist, and
      prazosin, an alpha 1-adrenoceptor antagonist, can modulate SS-like
      immunoreactivity (SS-LI) levels, binding of [125I][Tyr11]SS to its specific
      receptors, the ability of SS to inhibit adenylate cyclase (AC) activity, and the
      guanine nucleotide binding regulatory protein G, and G., in the Sprague-Dawley
      rat frontoparietal cortex. An IP dose of 2 or 4 mg/kg of phenylephrine injected 7
      h before decapitation decreased the number of SS receptors and increased the
      apparent affinity in frontoparietal cortex membranes. An IP dose of 20 or 25
      mg/kg of prazosin administered 8 h before decapitation increased the number of SS
      receptors and decreased their apparent affinity. The administration of prazosin
      before the phenylephrine injection prevented the phenylephrine-induced changes in
      SS binding. The addition of phenylephrine and/or prazosin 10(-5) M to the
      incubation medium changed neither the number nor the affinity of the SS receptors
      in the frontoparietal cortex membranes. Phenylephrine or prazosin affected
      neither SS-LI content nor the basal or forskolin (FK)-stimulated AC activities in
      the frontoparietal cortex. In addition, SS caused an equal inhibition of AC
      activity in frontoparietal cortex membranes of phenylephrine-and prazosintreated
      rats compared with the respective control group. Finally, phenylephrine and
      prazosin did not vary the pertussis toxin (PTX)-catalyzed ADP ribosylation of Gi-
      and/or Go-proteins. These results suggest that the above-mentioned changes are
      related to the phenylephrine activation of alpha 1-adrenoceptors or to the
      blocking of these receptors by prazosin. In addition, these data provide further
      support for a functional interrelationship between the alpha 1-adrenergic and
      somatostatinergic systems in the rat frontoparietal cortex.

PMID- 8745059
TI  - Somatostatin binding capacity, guanylate cyclase and tyrosine phosphatase
      activities during pancreatic proliferation in the rat induced by gastrectomy.
AB  - Gastrectomy increased pancreatic growth and this effect was associated with an
      increase in the number of somatostatin-14 (SS) receptors (146% of control)
      without altering their affinity. SS increased guanylate cyclase activity twofold
      in pancreatic acinar membranes from gastrectomized rats. The gastrectomy
      decreased pancreatic SS-like immunoreactivity (SS-LI) content (55% of control
      levels) and tyrosine phosphatase activity (74% of control levels). Administration
      of proglumide (20 mg/kg, IP), a gastrin/cholecystokinin (CCK) receptor
      antagonist, suppressed the inhibitory effect of gastrectomy on basal tyrosine
      phosphatase activity and SS-LI content, which returned to control levels.
      Furthermore, proglumide suppressed the increase of the number of SS receptors and
      of SS-stimulated guanylate cyclase activity induced by gastrectomy. All this
      suggests that pancreatic acinar cell growth is associated with upregulation of SS
      receptors, which could represent a mechanism promoted by the cell to negatively
      regulate the mitogenic activity of pancreatic growth factors such as CCK. In
      addition, the results also suggest that the negative regulation of tyrosine
      phosphatase activity may be important in the events involved in the pancreatic
      hyperplasia observed after gastrectomy.

PMID- 8745060
TI  - Characterization of growth hormone-releasing hormone (GHRH) binding to cloned
      porcine GHRH receptor.
AB  - To study structure-activity relationships of growth hormone-releasing hormone
      (GHRH), a competitive binding assay was developed using cloned porcine
      adenopituitary GHRH receptors expressed in human kidney 293 cells. Specific
      binding of [His1, 125I-Tyr10,Nle27]hGHRH(1-32)-NH2 increased linearly with
      protein concentration (10-45 micrograms protein/ tube). Binding reached
      equilibrium after 90 min at 30 degrees C and remained constant for at least 240
      min. Binding was reversible to one class of high-affinity sites (Kd = 1.04 +/-
      0.19 nM, Bmax = 3.9 +/- 0.53 pmol/mg protein). Binding was selective with a rank
      order of affinity (IC50) for porcine GHRH (2.8 +/- 0.51 nM), rat GHRH (3.1 +/-
      0.69 nM), [N-Ac-Tyr1, D-Arg2]hGHRH(3-29)-NH2 (3.9 +/- 0.58 nM), and [D
      Thr7]GHRH(1-29)-NH2 (189.7 +/- 14.3 nM), consistent with their binding to a GHRH
      receptor. Nonhydrolyzable guanine nucleotides inhibited binding. These data
      describe a selective and reliable method for a competitive GHRH binding assay
      that for the first time utilizes rapid filtration to terminate the binding assay.

PMID- 8745061
TI  - Human plasma DSIP decreases at the initiation of sleep at different circadian
      times.
AB  - Nocturnal plasma delta sleep-inducing peptide-like immunoreactivity (DSIP-LI) was
      determined serially in seven healthy male subjects. Time courses during nocturnal
      sleep (2300-0800 h), nocturnal sleep deprivation (2300-0500 h), and morning
      recovery sleep (0500-0800 h) after sleep deprivation were compared. A significant
      decrease in plasma DSIP-LI was found at the transition from wakefulness to sleep
      in both evening sleep (2300 h) and morning recovery sleep (0500 h). Time courses
      were accompanied by physiological changes in sleep electroencephalographic slow
      wave activity, and in plasma concentrations of cortisol and human growth hormone.
      No sleep stage specificity was found. It is concluded that DSIP is influenced by
      the initiation of sleep.

PMID- 8745062
TI  - Differential effects of transforming growth factor-beta on osteoclast-like cell
      formation in mouse marrow culture: relation to the effect of zinc-chelating
      dipeptides.
AB  - The effect of transforming growth factor-beta (TGF-beta) on osteoclast-like cell
      formation in mouse marrow culture in vitro was investigated. The bone marrow
      cells were cultured for 7 days in alpha-minimal essential medium containing a
      well-known bone resorbing agent. Osteoclast-like cell formation was estimated
      with staining for tartrate-resistant acid phosphatase (TRACP), a marker enzyme of
      osteoclasts. The presence of TGF-beta (10(-13)-10(-11) M) caused a significant
      increase in the number of osteoclast-like multinucleated cells (MNCs); the
      maximum effect was seen with 10(-12) MTGF-beta. With a higher concentration (10(
      10) M) of TGF-beta, the growth factor dramatically inhibited the 1,25
      dihydroxyvitamin D5 [1,25(OH)2D3; 10(-8) M]-induced formation of osteoclast-like
      MNCs. This inhibitory effect was also seen in the formation of osteoclast-like
      MNCs stimulated by parathyroid hormone (10(-8) M), prostaglandine E2 (10(-6) M),
      and interleukin-1 alpha (50 U/ml). The stimulatory effect of TGF-beta (10(-12) M)
      on osteoclast-like MNCs formation was inhibited by zinc sulfate (10(-6) M) or
      zinc-chelating dipeptide [beta-alanyl-L-histidinato zinc (AHZ), 10(-6) M]. The
      stimulating effect of TGF-beta was markedly weakened by the presence of EGTA (0.5
      mM), a chelator of Ca2+. The inhibitory effect of zinc compounds was not seen in
      the presence of EGTA. Moreover, the inhibitory effect of TGF-beta (10(-10) M),
      zinc sulfate (10(-6) M), or AHZ (10(-6) M) on osteoclast-like MNCs formation was
      not demonstrated in mature osteoclastic cells, although calcitonin (3 x 10(-8) M)
      significantly inhibited the osteoclastic formation. The present study
      demonstrates that TGF-beta has a stimulating and an inhibiting effect on
      osteoclast-like cell formation in mouse marrow culture, and that zinc can inhibit
      the stimulatory effect of TGF-beta.

PMID- 8745063
TI  - Molecular characterization of calcitonin gene-related peptide (CGRP) in a rat
      medullary thyroid carcinoma cell line.
AB  - The rat medullary thyroid carcinoma cell line, CA-77, is known to express the
      calcitonin gene and the cell line has been used for characterization of
      procalcitonin. The present investigations concentrate on a molecular
      characterization of the calcitonin gene-related peptide (CGRP) expressed by a
      subclone of this cell line. The investigations demonstrate that this subclone
      produces significantly more CGRP compared to calcitonin. Gel chromatography of
      cell extracts demonstrates heterogeneity for both CGRP and calcitonin, but a
      significant amount of immunoreactivity elutes corresponding to the elution
      position for synthetic CGRP and calcitonin, respectively. The gel chromatogram
      for CGRP demonstrates four immunoreactive peaks with Kd of 0.42, 0.53, 0.68, and
      0.85. The immunoreactive peak with Kd 0.42 elutes corresponding to synthetic rat
      CGRP. The four immunoreactive peaks were characterized by high pressure liquid
      chromatography followed by sequence analysis and mass spectrometry. The
      immunoreactive peak with Kd 0.42 was identified as rat alpha-CGRP as was the peak
      with Kd 0.53. The peak with Kd 0.68 was identified as 19-37 rat alpha-CGRP and
      the peak with Kd 0.85 as 28-37 rat alpha-CGRP. In summary, we find that the CA-77
      cell line expresses large quantities of normally processed amidated alpha-CGRP
      and specific fragments thereof. However, the cell line does not express
      detectable levels of rat beta-CGRP. The findings indicate that the CA-77 cell
      line can be useful for studies of calcitonin/CGRP gene expression.

PMID- 8745064
TI  - Calcitonin gene-related peptide and its receptor in the thymus.
AB  - Calcitonin gene-related peptide (CGRP), a 37-amino acid residue neuropeptide, was
      immunostained in rat thymus at two sites: a subpopulation of thymic epithelial
      cells, namely subcapsular/perivascular cells, were heavily stained besides some
      nerve fibers surrounding arteries and arterioles. The administration of nanomolar
      concentrations of rat alpha-CGRP dose-dependently raised intracellular cyclic
      adenosine monophosphate (cAMP) levels in isolated rat thymocytes (half-maximum
      stimulation 1 nM) but not in cultured rat thymic epithelial cells. Peptides
      structurally related to CGRP (i.e., rat calcitonin or amylin) had no effect.
      CGRP(8-37), an N-terminally truncated form, acted as an antagonist. Peripheral
      blood lymphocytes did not respond to CGRP, suggesting that receptors are present
      only on a subpopulation of thymocytes but not on mature T cells. This was
      substantiated by visualization of CGRP receptors on single cells by use of CGRP
      gold and -biotin conjugates of established biological activity: only a small
      proportion of isolated thymocytes was surface labeled. In situ, the CGRP
      conjugates labeled receptors on large thymocytes residing in the outer cortical
      region of rat thymus pseudolobules. Thus, immunoreactive CGRP is found in
      subcapsular/perivascular thymic epithelial cells and acts via specific CGRP
      receptors on thymocytes by raising their intracellular cAMP level. It is
      suggested that CGRP is a paracrine thymic mediator that might influence the
      differentiation, maturation, and proliferation of thymocytes.

PMID- 8745065
TI  - Effect of motilin on the L-leucine transport in rabbit jejunum.
AB  - Motilin is a gastrointestinal peptide that stimulates the gastrointestinal
      motility in several species. The aim of the present work has been to determine
      the effect of motilin on the L-leucine absorption in rabbit jejunum. The results
      show that motilin inhibits the L-leucine Na(+)-dependent system of transport
      located in the mucosal border mainly by diminishing the apparent Vmax. Motilin
      did not directly affect the Na(+)-dependent system of transport, but it seems to
      act across the protein kinase C (PKC). These results suggest that motilin may act
      as a regulatory hormone of the intestinal absorption of nutrients.

PMID- 8745066
TI  - Anorectic and neurochemical effects of pituitary adenylate cyclase activating
      polypeptide in rats.
AB  - Pretreatment of rats with intrahypothalamic injections of pituitary adenylate
      cyclase activating peptide (PACAP) 10 min prior to the injection of neuropeptide
      Y (NPY) significantly reduced food and water intake during the 4-h measurement
      period. Intrahypothalamic injection of PACAP in schedule-fed rats also reduced
      food and water intake for 2 h. A smaller 1-h reduction of water intake was
      observed in water-deprived rats, suggesting that the anticonsummatory effects of
      PACAP were primarily against food intake. PACAP treatment did not alter
      hypothalamic concentration of NPY, nor were neurotransmitters, precursors, or
      metabolites altered substantially in corpus striatum or nucleus accumbens
      regions. These results demonstrate primary anorectic effects of intrahypothalamic
      injection of PACAP. The demonstration of these anorectic effects may suggest a
      role of cyclic AMP activation and inhibition in the control of satiety and
      hunger.

PMID- 8745067
TI  - Endogenous opiates: 1994.
AB  - This article is the 17th installment of our annual review of research concerning
      the opiate system. It includes papers published during 1994 involving the
      behavioral, nonanalgesic, effects of the endogenous opiate peptides. The specific
      topics covered this year include stress; tolerance and dependence; eating;
      drinking; gastrointestinal, renal, and hepatic function; mental illness and mood;
      learning, memory, and reward; cardiovascular responses; respiration and
      thermoregulation; seizures and other neurological disorders; electrical-related
      activity; general activity and locomotion; sex, pregnancy, and development;
      immunological responses; and other behaviors.

PMID- 8745068
TI  - Comparative maps: the mammalian jigsaw puzzle.
AB  - Chromosomal rearrangements such as inversions and translocations have played an
      important role in defining genome organization in existing mammals. The number of
      rearrangements that have occurred since divergence from the 'primordial' mammal
      has been modest and the distribution of these rearrangements among chromosomes
      seems to be random. As a result, each mammalian species has a unique arrangement
      of conserved and disrupted chromosomal segments as compared to other mammalian
      species. Genes are excellent markers for these chromosomal segments because
      homologies can be detected in highly divergent species. By comparing the
      chromosomal location of homologous genes in different species, maps of conserved
      chromosomal segments can be obtained. These comparative maps can be used to
      predict gene locations in other species, identify candidate disease genes,
      characterize the genetic basis for complex traits, and find modulators of disease
      susceptibility. Equally important is the use of comparative maps for addressing
      questions about genome organization and evolution.

PMID- 8745069
TI  - Cereal genome evolution: pastoral pursuits with 'Lego' genomes.
AB  - The rapid progress in comparative analysis of cereal genomes reveals that they
      are composed of similar genomic building blocks. It seems that by simply
      rearranging these blocks and amplifying some of the repetitive sequences
      contained within them, it is possible to reconstitute the 56 different
      chromosomes found in wheat, rice, maize, sorghum, millet and sugarcane.
      Comparison of the orders of blocks in these reconstituted chromosomes reveals
      that the cleavage of a single chromosome formed from the blocks could give rise
      to all the combinations found in the chromosomes of the above species. A
      framework is now in place for collating all the information which has been
      generated from studying the individual cereals.

PMID- 8745070
TI  - Bovine genome mapping: evolutionary inference and the power of comparative
      genomics.
AB  - All bovine chromosomes are now represented by a syntenic group, a linkage map and
      at least one in situ hybridization. Almost 1,000 loci are mapped, about 300 of
      which are coding sequences useful for comparative mapping and evolutionary
      inference. Economically important loci are beginning to appear on bovine linkage
      maps and enhanced comparative maps are likely to be necessary to identify many of
      these genes by a comparative positional candidate gene approach.

PMID- 8745071
TI  - Genome evolution in enteric bacteria.
AB  - For more than a decade, the study of bacterial evolution has been dominated by
      the comparative analysis of nucleotide sequences within and among species. This
      approach, combined with the characterization of extensive regions of the
      chromosome by pulsed-field gel electrophoresis, has led to new insights into the
      dynamics of bacterial genomes.

PMID- 8745072
TI  - Coadaptation and immunodeficiency virus: lessons from the Felidae.
AB  - The emergence of pathogenic viruses in new species offers an unusual opportunity
      to monitor the coadaptation of viruses and their hosts in a dynamic ongoing
      process of intense biological selection. Tracking lentivirus epidemics in man,
      monkeys and cats reveals genomic struggles at three levels: quasispecies
      divergence within an individual; coadaptation of virus and host genomes
      subsequent to disease outbreaks; and transmission, spread and pathogenesis in
      related host species. Aspects of each level are revealed by examining the genetic
      diversity of feline immunodeficiency virus in domestic and wild cat species. This
      approach has been facilitated by the recent genetic characterization of a novel
      lentivirus in lions.

PMID- 8745073
TI  - Return of the H-word (heterochromatin).
AB  - Recent advances in studies of yeast, Drosophila and humans have renewed interest
      in heterochromatin. These recent studies have demonstrated the interspersion and
      rapid spread of transposable elements into Drosophila heterochromatin; documented
      the requirement of heterochromatic genes for heterochromatin; identified
      heterochromatin-like regions in yeast chromosomes; confirmed an important role
      for satellite DNA in human centromere function; and suggested potential functions
      for heterochromatin-associated proteins.

PMID- 8745074
TI  - The elusive centromere: sequence divergence and functional conservation.
AB  - The centromere is an essential cis-acting structure present in the chromosomes of
      all eukaryotes, central to the mechanism that ensures proper segregation during
      meiosis and mitosis. Molecular characterization of centromeres in the budding and
      fission yeasts has advanced significantly over the last few years due to their
      relatively small size and the availability of functional assays. However,
      identification and characterization of centromeric sequences from multicellular
      organisms has proven to be slow and difficult in the absence of direct functional
      tests. Molecular data have recently become available on the centromere of
      Drosophila, making it possible to bridge a long-standing gap in our knowledge on
      the general structure of centromeres. An evaluation of the available data from
      yeast to man suggests that centromere sequence and centromere sequence
      organization have diverged significantly, even amongst different chromosomes of a
      single organism; however, overall centromere organization and kinetochore
      components might be significantly more conserved than thought previously.

PMID- 8745075
TI  - Genomic regulation of transposable elements in Drosophila.
AB  - Transposable elements are a major source of genetic change, including the
      creation of novel genes, the alteration of gene expression in development, and
      the genesis of major genomic rearrangements. They are ubiquitous among
      contemporary organisms and probably as old as life itself. The long coexistence
      of transposable elements in the genome would be expected to be accompanied by
      host-element coevolution. Indeed, the important role of host factors in the
      regulation of transposable elements has been illuminated by recent studies of
      several systems in Drosophila. These include host factors that regulate the P
      element, a host mutation that renders the genome permissive for gypsy
      mobilization and infection, and newly induced mutations that affect the
      expression of transposon insertion mutations. The finding of a type of hybrid
      dysgenesis in D. virilis, in which multiple unrelated transposable elements are
      mobilized simultaneously, may also be relevant to host-factor regulation of
      transposition.

PMID- 8745076
TI  - Evolution of the intron-exon structure of eukaryotic genes.
AB  - The origin and evolution of intron-exon structures continue to be controversial
      topics. Two alternative theories, the 'exon theory of genes' and the 'insertional
      theory of introns', debate the presence or absence of introns in primordial
      genes. Both sides of the argument have focused on the positions of introns with
      respect to protein and gene structures. A new approach has emerged in the study
      of the evolution of intron-exon structures: a population analysis of genes. One
      example is the statistical analysis of intron phases--the position of introns
      within or between codons. This analysis detected a significant signal of exon
      shuffling in the DNA sequence database containing both ancient and modern exon
      sequences: intron phase correlations, that is, the association together within
      genes of introns of the same phase. The results of this analysis suggest that
      exon shuffling played an important role in the origin of both ancient and modern
      genes.

PMID- 8745077
TI  - Evolution of ATP-binding cassette transporter genes.
AB  - The transport of molecules across lipid membranes is an essential function of all
      living organisms. One of the families of genes that have evolved to carry out
      this function is that which encodes the ATP-binding cassette proteins. These
      molecules use active transport to pump specific molecules across membranes, and
      the genes that encode them are found in abundance in the genomes of both
      prokaryotes and eukaryotes. By using gene disruption techniques and by studying
      homologous genes in model organisms, significant progress has been made during
      the last few years in evaluating the physiological functions of ABC proteins in
      higher eukaryotes.

PMID- 8745078
TI  - DNA excision repair and transcription: implications for genome evolution.
AB  - The past two years have seen a substantial increase in knowledge regarding the
      enzymology of DNA excision repair. These data support a growing body of
      information which suggests that transcribed nucleotide sequences are
      preferentially subject to excision repair. It is possible that these mechanisms,
      or related ones, are relevant to the molecular evolution of sequences that appear
      not to evolve according to models which do not take into account regional
      sequence differences in the extent of DNA repair.

PMID- 8745079
TI  - Chromosome painting in mammals as an approach to comparative genomics.
AB  - Chromosome painting has become a routine tool in comparative cytogenetics. The
      utility of interspecies chromosome painting has been demonstrated in taxa
      characterized by highly rearranged karyotypes such as in rodents and lesser apes.
      Chromosome painting also provides a new level of precision in comparative genome
      analysis for eliminating errors of confounding convergence with homology. Recent
      results hold promise that molecular cytogenetics will make a significant
      contribution to the understanding of the major features of genome evolution.

PMID- 8745080
TI  - Phylogeny and natural history of the primate lentiviruses, SIV and HIV.
AB  - Studies of primate lentivirus phylogeny over the past decade have established a
      minimum of five related, but genetically distinct, groups of simian
      immunodeficiency virus (SIV), each originating from a different African primate
      species. The hypothesis that HIV-2 (and SIVmac) arose by cross-species
      transmission from sooty mangabeys (Cercocebus atys has been strengthened by a
      more detailed characterization of the SIVsm/SIVmac/HIV-2 group of viruses. SIV
      from all four subspecies of African green monkeys (SIVagm) have been
      characterized with an apparent chimeric genome structure of SIVagm from West
      African green monkeys. Although these naturally infected primates remain healthy,
      cross-species transmission to other primate species may result in
      immunodeficiency, as caused by SIVsm infection of macaque monkeys (Macaca sp.)
      and recently, SIVagm infection of pig-tailed macaques (M. nemestrina). Studies of
      variation within infected individuals have been facilitated by adaptation of the
      techniques of heteroduplex analysis and single-stranded conformational
      polymorphism of PCR generated fragments.

PMID- 8745081
TI  - The natural history and evolution of human and simian T cell
      leukemia/lymphotropic viruses.
AB  - The past five years have seen significant advances in understanding the origin
      and evolution of human T-cell leukemia/lymphotropic virus types I and II. The
      highlights include the identification of human T-cell leukemia/lymphotropic virus
      types I and II genotypic variants in remote human populations and the discovery
      of widely divergent simian T-cell leukemia virus in African and Asian non-human
      primates.

PMID- 8745082
TI  - LTR-retrotransposons and MITEs: important players in the evolution of plant
      genomes.
AB  - Retrotransposons are an abundant and ancient component of plant genomes, yet
      recent evidence indicates that element activity in many modern plants is
      restricted to times of stress. Stress activation of plant retrotransposons may be
      a significant factor in somaclonal variation, in addition to providing an
      important means to isolate new active elements. Long terminal repeat
      retrotransposons and a second class of elements we have called miniature inverted
      repeat transposable elements (MITEs) have recently been found to be associated
      with the genes of diverse plants where some contribute regulatory sequences.
      Because of their sequence diversity and small size, MITEs may be a valuable
      evolutionary tool for altering patterns of gene expression.

PMID- 8745083
TI  - Genomes and evolution.

PMID- 8745084
TI  - Major ethical problems confronting perinatal care around the world.
AB  - Some 7 million perinatal deaths occur throughout the world each year, 98% in
      developing countries. Most of these are preventible. The underlying socio
      economic, ethical and medical problems are reviewed in terms of their prevention
      and the optimal use of scarce resources. In particular, there is an urgent need
      to control population growth by raising the status of women and providing better
      and more accessible family planning services. Greater emphasis needs to be given
      to the development of primary health care in developing countries. In the
      foreseeable future, community maternal and newborn care is likely to rely on
      trained traditional birth attendants, with referral medical facilities when
      required. Breast feeding remains the most important priority in newborn care.
      Education of parents and young children holds the key to progress.

PMID- 8745085
TI  - Intrauterine death and infections during pregnancy.
AB  - OBJECTIVE: To elucidate whether microbial infections are involved in the etiology
      of intrauterine death. METHODS: One hundred four cases of stillbirth of unknown
      etiology and 96 age- and parity-matched referents with live births were analyzed
      with respect to microbial infection by cultures from the placenta, endocervix and
      internal organs of the fetuses, external sites of the babies and fetuses, and by
      serology for bacteria, viruses and Toxoplasma gondii. RESULTS: In 17 cases in
      whom no other infectious agent was diagnosed, Escherichia coli was isolated from
      the placenta and one or more internal fetal organs. Tests for Treponema pallidum
      and Toxoplasma gondii were more frequently positive in cases than in referents
      (O.R. 8.3 and 3.9, respectively). There was no increased risk for intrauterine
      death in women with human immunodeficiency virus, cytomegalovirus, herpes simplex
      virus or rubella virus. CONCLUSIONS: Our findings indicate that infections remain
      an important cause of intrauterine death in Zimbabwe.

PMID- 8745086
TI  - Decrease in severity of intrauterine growth retardation in subsequent
      pregnancies.
AB  - OBJECTIVE: Intrauterine growth retardation (IUGR) is likely to recur in a
      subsequent pregnancy. We investigated the obstetric features of recurrent cases
      and the severity of IUGR by comparing initial and subsequent deliveries. METHODS:
      From a total of 12,567 deliveries, 95 women who were delivered of small-for
      gestational-age (SGA) infants and who became pregnant again within 5 years, were
      enrolled. A retrospective, comparative study of recurrent and non-recurrent
      groups was performed. RESULTS: Twenty-two of ninety-five women gave birth to SGA
      infants again, and a relatively high risk of recurrence was confirmed, but no
      single recurrence-associated features were revealed. Within the recurrent group,
      the degree of IUGR was more severe in only five cases in the subsequent
      pregnancy. CONCLUSIONS: IUGR tends to recur, but does not increase in severity in
      most cases. We conclude that there is no need for excessive concern about the
      recurrence of IUGR.

PMID- 8745087
TI  - Sample adequacy in detecting Chlamydia trachomatis.
AB  - OBJECTIVE: Chlamydia trachomatis is an important etiological agent in female
      genital infection and may result in infertility. In recent years rapid diagnostic
      methods have become widely used as alternatives to cell culture. Our objective
      was to evaluate the technique of direct fluorescence assay (DFA) in estimating
      the presence of C. trachomatis. METHODS: Specimens taken from 40 infertile and 20
      fertile women were examined by DFA for the presence of C. trachomatis. RESULTS:
      Six of forty (15%) infertile women were found to be positive whereas no positive
      specimens were detected in the control group. When the specimens were grouped
      into those which were adequate or inadequate, 19 and five specimens,
      respectively, were adequate in the infertile and healthy groups. If only adequate
      specimens are included in estimating the presence of Chlamydia, the percentage is
      31.6%. CONCLUSIONS: In order to use DFA as a more reliable and rapid diagnostic
      test of C. trachomatis in female genital infection, false-negativity must be
      eliminated. Specimens must be collected adequately and concentrated in order to
      achieve optimal diagnostic success.

PMID- 8745088
TI  - Serum neopterin levels in ovarian tumors.
AB  - OBJECTIVES: The aims of this study were to evaluate the difference between benign
      and malignant ovarian tumors through measurement of preoperative serum neopterin
      and CA 125 levels and to evaluate the correlation between serum neopterin levels
      and prognosis. METHODS: Preoperative serum neopterin levels were measured in 55
      ovarian tumors. Of these, 29 malignant tumors were studied over a 3-year follow
      up period. RESULTS: Statistical analysis demonstrated significant differences in
      neopterin levels between those with benign or malignant ovarian tumors, and
      different survival rates between the 11 patients whose preoperative neopterin
      levels were > or = 7.9 nM/l and the 18 patients whose preoperative neopterin
      levels were < 7.9 nM/l (P < 0.01). The sensitivity of preoperative serum
      neopterin levels (> or = 7.9 nM/l) in detecting malignant ovarian tumors was
      37.9%, the specificity was 96.1%, the positive predictive value 72.0%, the
      negative predictive value 63.3% and the diagnostic efficiency 65.4%, and those of
      preoperative serum CA 125 levels (> or = 35 U/ml) in detecting malignant ovarian
      tumors were 62.1%, 73.1%, 91.7%, 58.1% and 85.5%, respectively. CONCLUSIONS:
      Measurement of preoperative serum neopterin levels helped to discriminate between
      benign and malignant ovarian tumors and was related to ovarian cancer survival.
      In particular the combination of CA 125 and neopterin measurements showed a
      better sensitivity for the diagnosis of ovarian cancer than neopterin alone.

PMID- 8745089
TI  - Medical treatment of squamous hyperplasia and lichen sclerosus of the vulva.
AB  - OBJECTIVE: To evaluate the efficacy of medical treatment in patients with lichen
      sclerosus (LS), squamous hyperplasia (SH) and lichen sclerosus with associated
      squamous hyperplasia. METHODS: Forty-eight patients with non-neoplastic
      epithelial disorders of the vulva, SH in 23 (47.9%), LS in 20 (41.6%) and LS with
      associated SH in five (10.5%) were diagnosed and treated in our clinic. Patients
      with LS were treated with 2% testosterone ointment. Topical fluorinated
      corticosteroids was the treatment of choice in patients with SH. Patients with LS
      with associated SH were treated with topical fluorinated corticosteroid
      application followed by testosterone propionate ointment. RESULTS: The clinical
      response rate of SH to first-line therapy was 95.6% with a correlation of 90.5%
      with histological reversal; this rate was 80% with a histological correlation of
      81.3% in LS. The remission rates of SH and LS patients following a full course of
      therapy were 100% and 90%, respectively. In LS with associated SH patients, 90%
      responded to standard therapy with a remission rate of 100% after completion of a
      full course of therapy. CONCLUSION: Medical therapy of lichen sclerosus and
      squamous hyperplasia was very effective with a good clinical and histologic
      correlation.

PMID- 8745090
TI  - Lymphadenectomy in stage-III serous cystadenocarcinoma of the ovary.
AB  - OBJECTIVE: To elucidate the effects of lymphadenectomy on the prognosis for
      ovarian cancer. METHOD: A retrospective study of 69 patients with stage-III
      serous cystadenocarcinoma was performed. RESULTS: Among the 69 patients, 36 were
      not treated by lymphadenectomy. Both pelvic and para-aortic lymphadenectomies
      were performed on 13 patients at the initial operation and on 11 at the second
      operation. The group (n = 13) treated by both pelvic and para-aortic
      lymphadenectomies at the initial operation had a disease-free survival rate that
      was significantly higher than the non-lymphadenectomy group (n = 36) or the group
      (n = 5) treated by pelvic or para-aortic lymphadenectomy alone (P < 0.04). These
      54 patients were subjected to multivariate analysis for lymphadenectomy at the
      initial operation, and a significant correlation was found between disease-free
      survival rate and both pelvic and para-aortic lymphadenectomies (P < 0.05).
      CONCLUSION: These results suggest that systematic lymphadenectomy can reduce the
      rate of recurrence.

PMID- 8745091
TI  - Chronic ectopic pregnancy after clinically successful methotrexate treatment of
      ectopic pregnancy.
AB  - Persistent ectopic pregnancy, often a sequelae of conservative surgical
      procedures, is characterized by a residual trophoblastic activity site with
      rising or plateauing beta-human chorionic gonadotropin (hCG) titers after the
      initial treatment. Chronic ectopic pregnancy is a different entity which may be
      seen after expectant management of ectopic pregnancy and contains no active
      trophoblast with low or absent beta-hCG titers. A rare case with features of a
      chronic ectopic pregnancy, which followed successful methotrexate medical
      treatment of a persistent ectopic pregnancy, is presented.

PMID- 8745092
TI  - Zonary placenta.
AB  - A primipara with an uncomplicated pregnancy was induced for labor. As uterine
      contractions commenced, an antepartum bleeding occurred, followed by fetal
      distress. An anemic fetus was delivered by cesarean section. The placenta was
      annular in shape with velamentous blood vessels, one of which was ruptured and
      sealed off by a fresh thrombus. A zonary or ring-shaped placenta is extremely
      rare: to our knowledge, this is the first case to be published.

PMID- 8745093
TI  - Asymptomatic endometrial carcinoma after endometrial ablation.
AB  - Endometrial ablation has been recently introduced as a surgical alternative to
      hysterectomy for the treatment of dysfunctional uterine bleeding. The procedure
      itself is reasonably safe. However, if occult endometrial cancer is present
      before the procedure and is not detected, it may be more difficult to diagnose
      later. Endometrial cancer may also arise de novo from missed endometrial tissue.
      Two cases of endometrial cancer following endometrial ablation have been
      reported, but its overall incidence is unknown. A 58-year-old woman was treated
      with endometrial ablation for dysfunctional uterine bleeding. Three years later
      she underwent hysterectomy and Marshall-Marchetti-Krantz procedure for urinary
      incontinence; incidental, asymptomatic endometrial adenocarcinoma was discovered.
      The final pathology was grade 1 adenocarcinoma, invading more than 50% of the
      myometrium (FIGO stage Ic). Endometrial cancer may occur following endometrial
      ablation and it may be asymptomatic. Careful patient selection and close follow
      up are essential.

PMID- 8745094
TI  - Bilateral tubal pregnancy treated with laparoscopy.

PMID- 8745095
TI  - Tampon-induced vaginal bleeding presenting as intermenstrual bleeding.

PMID- 8745096
TI  - Successful treatment of catamenial pneumothorax with danazol.

PMID- 8745097
TI  - Sexual dysfunction.
AB  - Sexual dysfunction may adversely affect a woman's self-esteem and her overall
      sense of well-being. The obstetrician-gynecologist can play an important role by
      asking the patient about any problems with sexual function. Physiologic changes,
      disease, surgery, or medical therapy may result in sexual dysfunction. The
      physician should recognize the potential effects of these conditions on a
      patient's sexuality and provide the patient with appropriate education and
      counseling. Patients should also be advised about alternatives for sexual
      expression, particularly after pelvic surgery. Specific support groups of others
      facing similar conditions may also be helpful. If, after taking a history of the
      patient's psychologic status, relationship, and a sexual history, the physician
      does not see an obvious cause and course of treatment, the best choice may be
      referral to a marriage or relationship counselor or a sexual therapist,
      particularly if the problem is of a psychologic nature or of long duration.
      Counseling or referral can be helpful and rewarding for the patient, her partner,
      and the physician.

PMID- 8745098
TI  - Early pregnancy loss.

PMID- 8745099
TI  - Vitamin A supplementation during pregnancy.

PMID- 8745100
TI  - Guidelines for diagnostic imaging during pregnancy. The American College of
      Obstetricians and Gynecologists.

PMID- 8745101
TI  - Population review: (2) are we healthier?
AB  - This article describes how OPCS statistics can be used to monitor health, to try
      and answer the question 'are we healthier?' Three aspects of health are covered:
      mortality, morbidity, and behaviour known to have an impact on health. The
      discussion covers only those statistics which measure health directly, rather
      than those deriving from the use of health services. The article does not put
      forward any particular definition of health nor does it attempt to draw together
      a single measure of health. It concentrates on the last 10-20 years and aims to
      cover the whole spectrum of age and sex groups. The model can be applied to any
      subgroup of the population.

PMID- 8745102
TI  - Mortality in regions and local authority districts in the 1990s: exploring the
      relationship with deprivation.
AB  - Regional and local authority patterns of mortality in England and Wales for both
      males and females are presented for the latest available years (1989-93). The
      familiar geographic pattern of higher mortality in the north and west and lower
      mortality to the south and east of the country has continued into the 1990s and
      there has been no significant widening or narrowing in the mortality gap between
      the worst and the best regions during the 1980s. The local authorities with
      higher mortality are still predominantly in urban areas. Using a modified form of
      the Department of Environment's 1991 deprivation index, mortality in more than
      350 English local authorities in 1989-93 was analysed to study the interaction
      between socio-economic and geographic variables. There is a very strong
      relationship between mortality and deprivation at the local authority level
      measured by this new index, with a tendency for higher mortality to be associated
      with greater deprivation. This relationship is most marked for males, but is
      still strong for females.

PMID- 8745103
TI  - A review of The health of our children, Decennial Supplement.
AB  - The health of our children, the second in OPCS's latest series of decennial
      supplements, brings together data from a wide variety of sources to paint a
      picture of the lifestyle and health of British children in the 1970s and 1980s.
      This review presents the main findings from the volume.

PMID- 8745104
TI  - Leprosy among the Limba: illness and healing in the context of world view.
AB  - The study analyzes the traditional beliefs and practices concerning leprosy of
      the Limba people of Sierra Leone. It shows that this dialectally diverse ethnic
      group has two views of leprosy and its cause, and two varieties of stigma
      associated with the disease. The Limba have abandoned their traditional
      treatments for leprosy in response to an effective leprosy control programme, but
      retained their traditional world view, including its definition of illness, which
      holds a person seriously ill only when he has severe pain or disability. Thus,
      they seek treatment from the programme, but often at a relatively advanced stage
      of the disease. The study shows that the Limba have reinterpreted the notion of
      'germs' as introduced by medical workers, and that leprosy control workers have
      their own misunderstandings of Limba beliefs and practices. The study points the
      way to improved communication between leprosy workers and Limba patients by
      focusing on the points at which their views differ, and by identifying concepts
      within Limba world view that can be adapted by leprosy workers to help convey
      their message. The study emphasizes the importance of world view as a key to
      understanding patient attitudes and behaviour in developing countries, and to
      making valid cross-cultural comparisons, but notes that it can take years for an
      investigator to understand the world view of a particular culture. It argues that
      in short-term research projects there is an advantage to working with an
      anthropologist who has in-depth knowledge of the culture, but who may not be a
      specialist in medical anthropology.

PMID- 8745105
TI  - Reconsidering the status of anorexia nervosa as a western culture-bound syndrome.
AB  - Based on Ritenbaugh's 1982 definition, this essay reconsiders the status of
      anorexia nervosa as a Western culture-bound syndrome (CBS). It argues that
      anorexia nervosa, in its culturally reconstructed fat phobic form, is no longer
      bound to specific Western localities. Instead, it may be conceived as being
      grounded in the transnational culture of 'modernity', characterized by an
      internationalised socio-economic stratum now found in many rapidly urbanising
      parts of the world, and composed of increased affluence, as well as the
      globalization of fat phobia and diffusion of biomedical technology. Although the
      treatment implication of Ritenbaugh's CBS concept may appear to be misplaced from
      the clinician's pragmatic perspective, its salience for clarifying the
      interaction of individual and cultural concerns in self-starvation, as well as
      for fostering a needed self-scrutiny in psychiatry, is affirmed. A critique of
      the dialectical relationship between culture and psychopathology is then put
      forward. This addresses the apparently conflicting role of anorexia nervosa in
      enacting as well as combating the cultural pursuit of thinness, and ends by
      highlighting the inadvertent influence of the biomedical establishment in
      propagating the condition with measures intended, ironically, for preventing it.

PMID- 8745106
TI  - Is general practitioner decision making associated with patient socio-economic
      status?
AB  - This paper presents a preliminary exploration into the relationship between
      decisions made by general practitioners (GPs) and the socio-economic status (SES)
      of patients. There is a large literature on the association between SES, health
      state and the use of health services, but relatively little has been published on
      the association between SES and decisions by clinicians once a patient is in the
      health system. The associations between GP decision making and the patient's SES,
      health status, gender and insurance status are examined using logit analysis.
      Three sets of binary choices are analysed: the decision to follow up; to
      prescribe; and to perform or to order a diagnostic test. Secondary data on
      consultations for a check up/examination were used to explore these
      relationships. The results suggest that SES is associated independently with the
      decision to test and the decision to prescribe but not with the decision to
      follow up. Patients of high SES are, ceteris paribus, more likely to be tested
      and less likely to receive a prescription compared with patients of low SES.
      Women are more likely to be tested and to receive a prescription than men. These
      findings have implications for the pursuit of equity as a goal of health services
      policy.

PMID- 8745108
TI  - Women and AIDS: an analysis of media misrepresentations.
AB  - A close reading of popular discourses on women and the AIDS epidemic reveals the
      ways in which such depictions produce and reiterate power-laden notions of
      normative sexuality. Prostitutes, one frequently depicted 'kind' of woman, are
      presented as indiscriminate, polluting to men and categorically different from
      'normal' women. Other women depicted in AIDS discourses are almost always HIV
      positive mothers or pregnant women; these women are usually only of concern
      insofar as they may infect their babies. The themes of self-control, self
      discipline and personal responsibility may also stigmatize women. Such discourses
      suggest that those who have AIDS are responsible for their own illness. They also
      deflect attention away from the socioeconomic contexts that may make it more
      difficult for some to avoid infection, away from the connections between poverty,
      illness and disempowerment, and away from systematic inequalities that
      characterize U.S. society.

PMID- 8745107
TI  - Educational differentials in mortality: United States, 1979-85.
AB  - The paper examines educational differentials in adult mortality in the United
      States within a multivariate framework using data from the National Longitudinal
      Mortality Survey (NLMS). As a preliminary step we compare the magnitude of
      educational mortality differentials in the United States to those documented in
      Europe. At ages 35-54, the proportionate reductions in mortality for each one
      year increase in schooling are similar in the United States to those documented
      in Europe. The analyses further reveal significant educational differentials in
      U.S. mortality among both men and women in the early 1980s. Differentials are
      larger for men and for working ages than for women and persons age 65 and above.
      These differentials persist but are reduced in magnitude when controls for
      income, marital status and current place of residence are introduced.

PMID- 8745109
TI  - Inequalities in health related to women's marital, parental, and employment
      status--a comparison between the early 70s and the late 80s, Norway.
AB  - Studies indicate that inequalities in women's health are associated with women's
      marital, parental and employment status. The causal mechanisms which generate
      these inequalities are linked to social change at the macro level. The present
      study asks whether patterns of ill-health according to women's statuses have
      changed during recent decades in Norway. Five national surveys 1968-91 are
      analyzed, using number of long-standing diseases as an indicator of health. The
      results indicate that health differences between full-time employed women and
      other employment statuses have increased during the 70s and 80s. As regards
      marital and parental status, the observed changes are not significant. The
      findings suggest that important causal mechanisms generating health differences
      related to marital status are located in the private sphere. The interpretation
      of the widening health gap between employed and non-employed women focuses both
      on developments which have made it easier to combine employment and family
      duties, on new norms which favour the self-esteem of employed women, and on
      health selection processes connected to welfare state developments.

PMID- 8745110
TI  - Dry sex in Zimbabwe and implications for condom use.
AB  - 'Dry sex' refers to the preference for a dry, tight vagina during sexual
      intercourse. Women in Zimbabwe and elsewhere have been found to use a variety of
      drying agents to achieve these effects. Previous studies of 'dry sex' have
      concentrated on documentation of the practice and investigation of any associated
      increased risk of HIV. In contrast, this study examines the impact of 'dry sex'
      on condom use and effectiveness. Focus group interviews were held with female
      HIV/AIDS peer educators in Zimbabwe who had a history of commercial sex work.
      Participants reported that drying agents had physical and psychological
      consequences. That is, agents were said to dry and tighten a woman's vagina, and
      also to serve as 'love potions' to attract sexual partners and ensure their
      faithfulness. Although vaginal dryness was not found to deter the use of condoms,
      some women were reluctant to use condoms for fear of blocking the 'magic' of
      drying agents. There was agreement among participants that condoms frequently
      broke when used in conjunction with drying agents. Participants primarily
      attributed condom breakage to excessive vaginal tightness. Lubricants were not
      routinely used during sex or with condoms. However, participants preferred the
      use of lubricated condoms when they used condoms. Implications of the 'dry sex'
      practice for AIDS prevention programs and development of new HIV prevention
      technologies are discussed.

PMID- 8745111
TI  - Gender response to neurofibromatosis 1.
AB  - This paper explores differing patterns of gender response to neurofibromatosis 1
      (NF1), a neurological genetic disorder. Perceptions of gender response expressed
      by persons with the condition and research findings about lifestyle and
      attitudinal differences related to the lived experience of coping with the
      condition and its consequences are discussed. Possible explanations for the
      causes of major social lifestyle differences between the genders are suggested.
      The data presented here have resulted from interviews with 30 affected
      individuals and parents of affected children recruited through NF support groups
      and from the caseloads of the Genetics Departments of two metropolitan hospitals.

PMID- 8745112
TI  - The role of clinical vignettes in rapid ethnographic research: a folk taxonomy of
      diarrhoea in Thailand.
AB  - This paper presents the findings of a rapid ethnographic research methodology
      used to investigate the beliefs and practices of rural mothers and grandmothers
      concerning diarrhoeal diseases in children under five years of age in Khon Kaen
      Province, Northeast Thailand. The multi-phase study used a combination of focus
      groups and clinical vignettes, semi-formal questionnaires and open-ended
      interviews. The efficiency of the combination of focus groups and clinical
      vignettes in obtaining an understanding of the important areas of belief in a
      short period of time is discussed, as well as the importance of quantifying and
      validating this information using other methodologies. A folk taxonomy of
      diarrhoea and its management is presented, and the implications of this for
      health planners is discussed. Most diarrhoea in children under one year is
      perceived to be su, a normal developmental stage which requires no treatment. As
      su is not considered to be diarrhoea, health messages concerning diarrhoea are
      not considered by care-givers. The labelling of a child with diarrhoea as having
      su results in a delay in help-seeking, a risk factor for dehydration. Thus su
      needs to be taken into consideration in health education campaigns. The
      informants demonstrated little understanding of the role of infection in
      diarrhoea, nor of the role of personal and domestic hygiene for its prevention,
      nor of the place and function of ORS, highlighting important areas where
      education is still necessary.

PMID- 8745113
TI  - Medical futility decisions and physicians' legal defensiveness: the impact of
      anticipated conflict on thresholds for end-of-life treatment.
AB  - Does legal defensiveness significantly influence physicians' assessments of
      medical futility, in ways that may adversely affect the rights of patients and
      their family members to make their own health care decisions at the end of life?
      This exploratory study addresses that question with attitudinal data from a
      survey of 301 physicians practicing in academic medical centers in Texas. The
      majority of respondents indicated that the probability of success defining futile
      treatment should hypothetically be lower for patients with potential to benefit
      more from life-sustaining medical intervention (e.g. typically patients who are
      sentient), and higher for patients with less potential to benefit (e.g. patients
      in a persistent vegetative state). That is to say, physicians normally perceive
      longer odds to be worth pursuing for greater potential gain - a position that
      seems logically consonant with patients' rational self-interest. However,
      physicians with an attitude of extreme legal defensiveness did not fit this
      pattern. Rather, they tended to define futility in a manner that would maximize
      the physician's latitude to justifiably oppose patient preferences for end-of
      life treatment abatement. These findings suggest that some physicians assume an
      adversarial position in their consideration of medical futility issues - an
      attitude that anticipates conflict with terminally-ill patients or their
      surrogates. The analysis presented here is not definitive, but at least raises
      the question of whether some physicians may inappropriately use their prerogative
      over medical futility as a means to guard their professional autonomy against
      perceived threats.

PMID- 8745114
TI  - Ethnography of fertility and menstruation in rural Mexico.
AB  - In rural populations in Mexico, the system of ideas in relation to the
      reproductive cycle is built on a mestizo base, with pre-Colombian and Western
      elements. The objective of the study was the analysis of concepts and resources
      related to human reproduction in Morelos, in order to design a primary
      reproductive health care program. The use of ethnographic methods helped identify
      bio-cultural constructs on which the communities base their reproductive
      patterns. Our main research results reveal that these populations attribute great
      value to the extension of the family through descendants. Women's sexuality is
      directly linked to reproduction and blood is the supremely feminine substance.
      Great importance is consistently attributed to menstruation about which well
      defined concepts exist in the community, where as pre-menarche changes are
      perceived as a state of bio-psychosocial maturity. Menarche beyond 14 years of
      age is considered abnormal and is attributed to an 'excess of cold' in the body,
      therapy is usually administered by traditional birth attendants. In the mythical
      explanations given for bleeding, the moon plays a fundamental role, as the first
      rupture of the hymen is attributed to it. A general lack of knowledge about
      ovulation and its relation to reproduction was observed, resulting in incorrect
      contraceptive practices.

PMID- 8745115
TI  - Prostitutes, prostitution and STD/HIV transmission in mainland China.
AB  - China's opening to the world has enabled massive social and economic
      transformations and the liberalization of many policies, but also the rise of
      coincident social problems and diseases. A revival of wide-scale female
      prostitution since the 1980s has now accelerated to a nationwide dilemma.
      Prostitutes have long been considered to be reservoirs, if not 'vectors' for the
      transmission of sexual diseases. A well established STD epidemic in the last
      decade, plus the presence of growing HIV infections in China now, underscore the
      need to evaluate the prostitute's role in STD and HIV propagation. This report
      examines unobtrusive data on female prostitutes in the People's Republic of China
      through an analysis of prison records from eight sexually segregated prisons (six
      in Sichuan Province and two in Guizhou Province), two female re-education
      institutions, and arrest records for convicted prostitutes from four counties in
      Sichuan Province and Chengdu City (also in Sichuan). Collectively, these data
      represent 2057 female prostitution cases, and span the years 1988-1990.
      Demographics are examined to enable a profile of the prostitute as based on data
      reviewed, and this is contrasted to the stereotype of the prostitute as described
      in government propaganda against prostitution. STD prevalence rates in the
      samples are examined and contrasted to two other studies on STDs in
      nonprostitution populations made available to the authors. Prostitute arrest
      records reveal a majority had active STD infection[s] at the time of their
      apprehension, with gonorrhea being the most common bacterium; in many instances,
      prostitutes also had a history of other sexually transmitted diseases. Thus, data
      examined support the notion of prostitution as an agent in STD transmission.
      Presence of HIV infection in prostitutes could not be corroborated through
      sampled records, nor could prostitution itself be confirmed as an agent in HIV
      transmission at present. However, given the type of clients serviced by
      prostitutes in China, a prostitute's own risk of HIV infection is discussed.
      Control measures by the Chinese government to curb prostitution are examined at
      both national and provincial levels. Questions are raised as to the effectiveness
      of present tactics as adjunctive strategies in reducing STD infection and HIV
      risk in the prostitution population.

PMID- 8745116
TI  - The performance of amnesic subjects on tests of delayed matching-to-sample and
      delayed matching-to-position.
AB  - Forced-choice tests of recognition have become the favoured behavioural method
      for the assessment of models of amnesia in nonhuman primates, yet the profile of
      deficits shown by human amnesic subjects remains uncertain. The present study
      explored the performance of 12 amnesic subjects on two delayed matching-to-sample
      tasks. Experiment 1, which used retention delays of between 2 and 60 sec,
      confirmed that amnesia impairs such tasks, even when there is only one item to be
      remembered. The results also highlighted the need to match levels of performance
      before the effects of delay can be interpreted. In Experiment 2 care was taken to
      eliminate ceiling effects and to match the subjects at the shortest delay (3
      sec). This was achieved by giving the control subjects harder versions of the
      same task. The amnesic subjects still showed a faster rate of forgetting for
      abstract patterns, indicating that this is a genuine feature of amnesia. In
      contrast, the amnesic subjects' performance on a spatial matching-to-sample task
      was not differentially affected by delays of up to 40 sec. There was no evidence
      that the amnesic subjects were disproportionately impaired on this spatial task,
      nor could the different aetiological groups be distinguished by their patterns of
      DMS performance.

PMID- 8745117
TI  - A case of 'sign blindness' following left occipital damage in a deaf signer.
AB  - We report on a right-handed, deaf, life long signer who suffered a left posterior
      cerebral artery (PCA) stroke. The patient presented with right homonymous
      hemianopia, alexia and a severe sign comprehension deficit. Her production of
      sign language was, however, virtually normal. We suggest that her syndrome can be
      characterized as a case of 'sign blindness', a disconnection of the intact right
      hemisphere visual areas from intact left hemisphere language areas. This case
      provides strong evidence that the neural systems supporting sign language
      processing are predominantly in the left hemisphere, but also suggests that there
      are some differences in the neural organization of signed vs spoken language
      within the left hemisphere.

PMID- 8745118
TI  - MEG based brain laterality: sex differences in normal adults.
AB  - Magnetoencephalographic (MEG) auditory evoked fields produced by short tone pips
      were recorded from 34 normal adults (17 males, 17 females) and the 100 msec
      latency component (M100) localized in left and right hemispheres. Absolute M100
      location in the antero-posterior dimension was calculated for each subject. M100
      sources were significantly further anterior in the right hemisphere of males.
      Magnetic resonance (MR) based anatomy of the superior temporal gyri (STG) in a
      subset of 17 subjects showed that in the left STG of both males and females M100
      sources were located approximately midway on the STG. In the right hemisphere of
      males, however, M100 sources were significantly further anterior on the STG than
      was the case for females. The findings are compatible with a sex based difference
      in right STG functional anatomy, with evidence of greater hemispheric
      lateralization in males compared to females based upon a predominantly right
      hemisphere contribution.

PMID- 8745119
TI  - Visual attention in Huntington's disease: the effect of cueing on saccade
      latencies and manual reaction times.
AB  - Studies of eye movements in patients with Huntington's disease (HD) have
      suggested that frontal lobe-basal ganglia structures are more involved in HD than
      the parietal lobes. To test this hypothesis further we compared the ability of HD
      patients and normal subjects to direct "covert" visual attention, using saccade
      latency and thumb press reaction time tasks that have been shown to be sensitive
      to parietal lobe dysfunction. Subjects were instructed to move their eyes or to
      press a button when a peripheral target was illuminated. The peripheral stimulus
      appeared at various intervals after the appearance of a central arrow(s) that
      pointed in the direction of the target (valid cue), in the opposite direction
      (invalid cue), or pointed simultaneously in both directions (neutral cue). For
      both saccade and thumb press paradigms, the difference in the latencies for
      trials with invalid and valid cues was the same in HD patients and normals. These
      findings suggest that the ability to direct visual attention is normal in HD and
      are compatible with the hypothesis that in HD, frontal-basal-ganglia circuits are
      more affected than parietal lobe pathways.

PMID- 8745120
TI  - On language laterality in normal dextrals and sinistrals: results from the
      bilateral object naming latency task.
AB  - Rasmussen and Milner [N.Y.Acad. Sci. Vol. 299, pp. 355-379, 1977] published data
      on late-lesioned (after age 6) epileptic patients who had suffered left
      hemisphere lesions. They estimated that left hemisphere dominance occurred in 96%
      of dextrals and 70% of sinistrals. These figures have been regarded as valid
      estimates for normal dextrals and sinistrals. We administered the Bilateral
      Object Naming Latency Task, a verbal tachistoscopic task with very good
      psychometric properties, to 188 dextral and 72 sinistral normals. Results showed
      that 93.6% of the dextrals and 80.3% of the sinistrals were left hemisphere
      dominant. A consideration of results from a number of carefully conducted
      dichotic listening studies suggests, as do present results, that the 70% left
      dominance estimate of Rasmussen and Milner for normal sinistrals may be too low
      by about 10%. It is suggested that 'bilateral dominance', present in 15% of the
      epileptic sinistrals of Rasmussen and Milner, may be much less common in normal
      sinistrals.

PMID- 8745121
TI  - Lateralization of predator-evasion response in a teleost fish (Girardinus
      falcatus).
AB  - Evidence of lateral asymmetries in the direction of turning during escape
      behaviour in a species of poeciliid fish, Girardinus falcatus, is reported. When
      repeatedly faced with a simulated predator (in five successive sessions, spaced 7
      days apart), immature Girardinus falcatus exhibited a significant population bias
      to turn right on the first session and a progressive bias to turn left in
      subsequent sessions. Mature Girardinus were then tested to check whether the
      shift in the direction of turn with repeated sessions depended on maturation or
      habituation. It was found that adult Girardinus showed a slight population bias
      to turn right in the first session and a strong subsequent bias to turn left
      after repeated sessions. The implications of these findings to our current
      understanding of the evolution of brain lateralization are discussed.

PMID- 8745122
TI  - Autobiographical memory and executive function in early dementia of Alzheimer
      type.
AB  - We studied executive function and autobiographical memory in a cohort of 33 DAT
      patients [divided into minimal (MMSE 24-30) and mild (MMSE 17-23) groups] and in
      30 normal controls. Autobiographical memory, as assessed by autobiographical
      fluency and the Autobiographical Memory Interview (AMI), was impaired in DAT
      patients, even those with minimal disease. There was evidence of a gentle
      temporal gradient on the incident but not the personal semantic component of the
      AMI, suggesting that the two components are dissociable. Executive function was
      assessed by two separate dual performance tasks and letter fluency. Although
      there was a trend for minimal DAT patients to be impaired on executive tasks,
      this only reached significance for the mild group. Regression analysis suggested
      that the divided attention component of working memory was involved in the
      retrieval of personal semantic autobiographical memory, but verbal fluency was
      more important in the retrieval of autobiographical incidents. There was thus a
      dissociation in the type of executive function implicated in different
      subcomponents of autobiographical memory, arguing for subcomponents within
      executive function and autobiographical memory. The autobiographical memory
      deficit in DAT reflects, we argue, both impairment in retrieval processes, linked
      to executive function, and a loss of memory stores.

PMID- 8745123
TI  - Mental representation of knowledge following frontal-lobe or postrolandic
      lesions.
AB  - The aims of this study were to examine the role of the prefrontal cortex in the
      representation of familiar activities using scripts, and to compare both
      Shallice's [Phil. Trans. Roy. Soc. Lond. B. Vol. 298, pp. 199-209, 1982] and
      Grafman's [Integrating Theory and Practice in Clinical Neuropsychology, pp. 93
      138, Lawrence Erlbaum, Hillsdale, New Jersey, 1989] models of schematic
      representation of knowledge. Twelve patients with frontal-lobe damage, nine with
      postrolandic lesions, and 13 normal control subjects were asked to generate
      actions belonging to six different scripts in a forward condition, and to two
      others in a backward condition. The latter condition was included to test
      Shallice's hypothesis that damage to the frontal lobes would only affect the
      execution of non-routine tasks. The results showed that patients with frontal
      lobe lesions produced scripts that were deprived of contextual elements and made
      more sequencing errors in the forward condition than matched normal control
      subjects, hence suggesting that the frontal cortex contributes to the production
      of an adequate mental representation of routine events. By contrast, the
      performance of the two clinical groups did not differ from the control subjects
      in their ability to generate scripts in the backward condition, although these
      three groups of subjects generated fewer actions in the latter condition. Further
      qualitative analyses demonstrated that patients with parietal-, but not with
      temporal-lobe lesions, produced sequencing errors in both forward and backward
      conditions. The latter findings suggest that the frontal lobes, together with the
      parietal cortex, may play a special role in establishing the spatio-temporal
      position of events within a script. The results of this study are discussed in
      terms of the recent models developed by Shallice and Grafman concerning the
      contribution of the frontal lobes in the mental representation of knowledge.

PMID- 8745124
TI  - Lateral and radial neglect as a function of spatial position: a case study.
AB  - We report a case of severe visuo-spatial neglect after multiple right-hemisphere
      infarcts. Experiment 1 demonstrated that the magnitude of transection
      displacement for the bisection of horizontal lines could be modulated by the
      lateral position of those lines within peripersonal space. As found in previous
      studies, neglect was attenuated when the true centre of the lines was to the
      right of the patient's midsagittal plane. In Experiment 2, radial lines were
      presented in left, middle, and right space. All bisections were placed too far
      from the body, but the magnitude of this effect increased significantly from
      right to left space. In Experiment 3, horizontal lines were presented at three
      distances within peripersonal space; there was a small but reliable reduction of
      bisection error for the most distally-placed stimuli. These results suggest that
      unilateral right hemisphere damage can distort the representation of space (and
      action therein) more extensively than is implied by the term left neglect.

PMID- 8745125
TI  - Transient left-sided alien hand with callosal and unilateral fronto-mesial
      damage: a case study.
AB  - A patient who showed a transient left alien hand after a subarachnoid
      haemorrhage, due to a ruptured aneurysm of the anterior communicating artery, is
      described. No left agraphia and left apraxia could be found. A CT-scan including
      coronal sections showed a right medial frontal hypodensity and different
      ischaemic lesions in the anterior part of the corpus callosum. The possible
      anatomic site of the lesion responsible for the permanent form of alien hand is
      discussed.

PMID- 8745126
TI  - Epidemiologists seek to discover and understand the determinants of disease that
      afflict people.

PMID- 8745127
TI  - Design issues in cohort studies.
AB  - Some basic features of cohort studies are reviewed along with a brief discussion
      of relative risk estimation procedures. This background, and a discussion of
      factors influencing cohort study power, provides a context to examine various
      cohort study design choices, including the choice of study population, the
      selection of cohort size and follow-up duration, cohort ascertainment and
      subsampling choices, and decisions concerning validation and reliability
      substudies. It is noted that confounding issues, and especially issues related to
      measurement error in the assessment of primary exposure and confounding
      variables, may have a major influence on the precision and reliability of cohort
      study analyses. A brief discussion is provided of the role of cohort studies in
      relation to other observational and experimental research strategies.

PMID- 8745128
TI  - Design issues in case-control studies.
AB  - The most difficult and most important considerations in planning the protocol of
      a case-control study are ascertainment of cases, selection of controls and the
      quality of the exposure measurement. Plans to ensure careful field work are
      equally important; without attention to data collection, the protocol will be
      meaningless. In most case-control studies, the measurement problem is magnified
      because one cannot implement the collection of exposure information at the
      beginning of follow-up, and instead must rely on interviews, existing records or
      extrapolation into the past. Consideration of a case-control study as an
      efficient way to study a cohort helps to resolve some design issues.

PMID- 8745129
TI  - Sample size determination in epidemiologic studies.
AB  - Sample size determination is an important issue in epidemiologic studies.
      Standard methods for determining sample size in cohort and case-control studies
      have generally been restricted to dichotomous disease and exposure variables and
      discrete confounding variables, and are based on simplifying assumptions that
      could often be unrealistic. Methods for sample size determination that make less
      restrictive and more realistic assumptions regarding the distribution of disease,
      exposure and confounding variables and which more closely parallel the analyses
      that are performed on the data, after the study has been conducted, have been
      developed in recent years. In this article some recent developments in the
      methodology for sample size determination in epidemiologic studies are reviewed.

PMID- 8745130
TI  - Study design for epidemiologic studies with measurement error.
AB  - Exposure measurement error in epidemiological studies is recognized as a feature
      that must be considered because of the potential bias that can result in
      estimates of the exposure-disease association. Most of the work to date has
      focused on methods of analysis that adjust for the resultant bias, but the
      implications of this work to the design of epidemiologic studies is not as well
      understood. An overview of the issues involved in the use of methods for dealing
      with errors in exposure information is discussed along with some design options
      that have been proposed for providing information necessary for their use.
      Validation studies compare somewhat crude and inexpensive measures of exposure to
      a gold standard, and study designs that incorporate these into the overall plan
      can realize some advantages in terms of cost. In addition, repeated assessments
      of exposure can realize efficiency for measures of exposure that are unbiased.
      However, much work remains to be done in the development of efficient designs for
      studying disease aetiology and prevention.

PMID- 8745131
TI  - Self-report stability for substance use over 10 years: data from the St. Louis
      Epidemiologic Catchment Study.
AB  - In substance abuse research many study protocols require the recall and report of
      behavior from the distant past that may affect reliability. This study addresses
      the stability of substance use reports over a 10-year follow-up period. We
      reinterviewed 223 ECA subjects who reported baseline drug use. Reports from
      baseline to follow-up were categorized as either incident cases, agreements, or
      discrepancies. Different patterns were found for each substance group. The
      authors found that cannabis, cocaine, sedatives, and opiates had high agreement
      rates ranging from 82-86% and amphetamines had the lowest (73%). Implications for
      future drug research are discussed.

PMID- 8745132
TI  - Effects of remoxipride, an atypical antipsychotic, on cocaine self-administration
      in the rat using fixed- and progressive-ratio schedules of reinforcement.
AB  - Remoxipride, a selective D2-dopamine receptor antagonist with preferential
      activity for mesolimbic-mediated behaviors, was assessed for its potential to
      block cocaine self-administration. The effects of remoxipride (RMX) were
      evaluated using fixed-ratio-1 (FR-1) and progressive-ratio (PR) schedules of
      reinforcement. On FR-1, RMX pretreatment increased the rate of cocaine
      injections, while on a PR, breaking points were reduced. Daily RMX treatment also
      resulted in breaking point reductions, but the decreases in cocaine's reinforcing
      potency did not result in extinction of cocaine intake and were not sustained
      upon cessation of RMX. Thus, RMX can reduce the rewarding effects of cocaine, and
      if safely tolerated over sustained periods of treatment it, or drugs with a
      similar pharmacological profile, could provide a therapeutic adjunct in the
      treatment of cocaine addiction.

PMID- 8745133
TI  - Incongruity between occupational interests and academic skills in drug abusing
      women.
AB  - This study assessed the occupational interests and academic skills of 50 patients
      of a center for addiction and pregnancy. Patient ratings of 31 occupations showed
      that a subset of ten occupations (telephone operator, cosmetologist, mail clerk,
      data entry operator, child care worker, receptionist, office clerk, word
      processor, billing clerk, secretary) were of interest to significantly more
      subjects than other occupations (P < or = 0.05). Most of the desired occupations
      were office jobs requiring basic skills not possessed by most study participants.
      Although participants had completed a mean (range) of 11 (8-15) years of
      education, their mean (range) grade levels of reading, spelling and arithmetic
      were estimated at 6.9 (0.8-12), 6.8 (1-12), and 5.7 (2-11.8) years, respectively.
      These data suggest that the study participants will need basic skills training to
      achieve their occupational goals. Importantly, patient ratings also indicated
      that most participants were interested in receiving the needed training. Overall,
      the study suggests that provision of basic academic skills training may improve
      the long-term employment outcomes of these drug abusing women.

PMID- 8745135
TI  - Screening for alcohol problems in the emergency room: a rapid alcohol problems
      screen.
AB  - This paper compares the sensitivity and specificity of a five-item Rapid Alcohol
      Problems Screen (RAPS) optimized in this sample with the CAGE, brief MAST, AUDIT,
      TWEAK, History of Trauma Scale and breathalyzer reading against ICD-10 criteria
      for alcohol dependence or harmful drinking, by gender, ethnicity and injury
      status in a probability sample of emergency room patients (n = 1330) from the
      University of Mississippi Medical Center. The RAPS performed better than all
      other screening instruments for the total sample of current drinkers who reported
      ever having had three or more drinks at one time (sensitivity of 90%, specificity
      of 78%), and performed consistently better across all subgroups than any other
      single instrument, even at alternate cut points. The Rapid Alcohol Problems
      Screen may hold promise for use in clinical settings in identifying those who
      could benefit from a brief intervention or referral for problem drinking,
      particularly since the instrument is short and patients need not be asked
      additional questions after screening positive on one of the five items. Further
      research is necessary to analyze and compare the performance of the RAPS with
      other screening instruments across demographic subgroups in other emergency room
      and primary care settings.

PMID- 8745134
TI  - A multicenter trial of bupropion for cocaine dependence in methadone-maintained
      patients.
AB  - We conducted a multi-site, placebo-controlled, randomized double-blind clinical
      trial comparing bupropion HCL (300 mg/day) to placebo for the treatment of
      cocaine dependence in methadone-maintained subjects. A total of 149 subjects at
      three sites participated in a 12-week study. Outcome measures included cocaine
      use, level of depression, and psychosocial functioning. Results showed no
      significant differences between placebo and bupropion. Exploratory analyses
      suggested a medication effect for the subset of subjects depressed at study
      entry. The need to target subgroups of cocaine abusers in future pharmacotherapy
      trials and the possible role of treatment readiness are discussed.

PMID- 8745136
TI  - Heroin addicts and methadone treatment in Albuquerque: a 22-year follow-up.
AB  - All heroin addicts who registered for methadone treatment in Albuquerque in 1969
      1971, 1019 in all, were the subjects of this follow-up study, conducted in 1991
      1993. The cohort was almost entirely of Hispanic (Chicano) ethnicity, 86% male,
      with median age 27 at entry. We located 776, dead or alive, and we were able to
      interview 243 concerning many aspects of their lives. At least one-third of the
      original group had died during the 22-year period, representing standard
      mortality ratios 4.0 for males and 6.8 for females. Drug overdose, violence,
      alcohol, or suicide accounted for nearly all deaths of which the causes were
      known. Despite the availability of treatment, including methadone maintenance,
      both heroin use and criminality continued at a high rate. Of the 428 known
      survivors, 48% were currently enrolled in a methadone program after 22 years.
      They were using significantly less heroin, alcohol, and other drugs (except
      nicotine) than those not on methadone. Similar beneficial effects of methadone
      maintenance were reported retrospectively at interview. Our findings offer an
      insight into heroin addiction as a chronic lifelong relapsing disease with a high
      fatality rate.

PMID- 8745137
TI  - Diagnostic tests for alcoholism in primary health care: compared efficacy of
      different instruments.
AB  - BACKGROUND: Alcoholism is an uncommon diagnosis in normal medical activity
      despite being a prevalent health problem in Spain. One of the main obstacles that
      make diagnosis difficult is the lack of valid, reliable instruments of detection.
      The aim of the present study is to validate different tests for diagnosing
      alcoholism (CAGE, Alcohol Clinical Index, MCV, GGT, GOT/GPT and GGT/AP) in
      primary care and compare their diagnostic efficacy. METHODS: The diagnostic
      efficacy and discriminating power of each of the tests were calculated from the
      results obtained from 219 patients (out of 698 aged over 15 years) who answered
      the CAGE questionnaire. Patients were selected from doctors surgeries in an urban
      health centre. The diagnosis of alcoholism was based on the presence of DSM-III
      criteria and/or a daily alcohol consumption of 60 grams or more in men and 30 or
      more in women. RESULTS: The CAGE questionnaire showed a sensitivity of 69.86% and
      specificity of 80.46%, with the cut-off point at 1. The remaining tests showed a
      poorer diagnostic efficacy. The CAGE questionnaire scoring was the parameter that
      best distinguished alcoholic patients from non-alcoholic patients. CONCLUSIONS:
      The CAGE questionnaire demonstrates the greatest efficacy and discriminating
      power for diagnosing patients with alcoholism in primary care.

PMID- 8745138
TI  - Inhalants to heroin: a prospective analysis from adolescence to adulthood.
AB  - Recent cross-sectional studies have indicated that inhalant use might be a
      vulnerability marker for the development of heroin use. This study is the first
      prospective investigation of the hypothesized association between early inhalant
      use and later heroin use. Analyses were conducted using longitudinal data from a
      community sample of Woodlawn (an all African American community on the South side
      of Chicago). Six-hundred subjects participated in both the adolescent and the
      adult assessments (approximately ages 16 and 32, respectively). Youths with a
      history of inhalant use by age 16 were over nine times more likely to begin
      heroin use by age 32, even when other plausible risk factors for the development
      of heroin use were held constant (RR = 9.3; 95% C.I. = 1.3 - 51.3). These
      findings add to and are consistent with prior cross-sectional evidence from data
      based on treatment samples and national survey data. The results from this
      longitudinal assessment support the idea that youthful inhalant use should be
      regarded as a vulnerability marker for the development of more serious drug use
      involvement in the form of heroin use.

PMID- 8745139
TI  - German mental health legislation and alcoholism treatment: results of a
      retrospective long-term study in a Berlin state mental health hospital.
AB  - In 1985 German mental health legislation underwent a transformation. In
      accordance with an international trend, the State of Berlin, a pacesetter in this
      field, introduced a Law for Mentally Diseased Patients (Gesetz fur psychisch
      Kranke). In contrast to the former Law for the Committal of the Mentally Ill and
      Substance Abusers (Gesetz uber die Unterbringung von Geisteskranken und
      Suchtigen) healing and recovery are the main aims which the legislation focuses
      on with the intention of avoiding committal by excluding patients with mild
      disorders from involuntary admission. The Karl-Bonhoeffer-Mental-Health
      Hospital's Department for Dependency Disorders conducted a study on 3014 alcohol
      dependent patients who were discharged between 1984-1990. The focus of the study
      was to determine predictors for involuntarily committal; patients were explored
      in respect to age, sex, length of stay, psychiatric disorders, their living
      situation and how they had been admitted. Moreover, attempts were made to
      discover whether the 1985 law had changed the patient profile or the frequency or
      length of treatment in comparison to the previously valid law.

PMID- 8745140
TI  - Predicting premorbid functioning in crack-cocaine abusers.
AB  - The Wide Range Achievement Test (Revised) (WRAT-R) reading test, demographic
      variables and drug use severity were used to develop prediction equations to
      estimate premorbid ability in 92 cocaine abusers. WRAT-R reading was correlated
      significantly with full scale, verbal and performance IQ. Stepwise regression
      indicated that only WRAT-R reading score and age accounted for 23% of the
      variance in Full Scale IQ (FSIQ) and 28% in Verbal IQ (VIQ). Abstinence and
      severity of use variables did not correlate with nor predict IQ. Actual and
      predicted IQ scores were correlated significantly and did not differ based on
      within group t-tests. Thus, these formulas accurately estimate premorbid
      functioning in cocaine-dependent research patients with FSIQs in the average to
      low average range, replicating the results in normal adults with average IQs.

PMID- 8745141
TI  - Non-competitive time-resolved immunofluorometric assays for determination of
      human insulin-like growth factor I and II.
AB  - We present sensitive non-competitive time-resolved immunofluorometric assays (TR
      IFMAs) for IGF-I and IGF-II based on monoclonal antibodies. Assays were performed
      in microtest-plate wells: the first antibodies were immobilized on the solid
      matrix, the second labelled with the chelate derivative of Europium (Eu3+). The
      obtained specificities and sensitivities were high: IGF-I and IGF-II cross
      reactivity in heterologous assay was below 0.0002%. The detection limits were
      0.0025 micrograms/l and 0.010 micrograms/l for the IGF-I and IGF-II assay,
      respectively. The operating range included upwards: 2.5 micrograms/l (IGF-I) and
      10.0 micrograms/l (IGF-II). This implies that all clinically relevant serum
      concentrations could be measured in one final dilution (1:1066 for IGF-I and
      1:2132 for IGF-II) after acid ethanol extraction. The high sample dilution with
      buffer made further neutralization or evaporation of serum acid ethanol extracts
      unnecessary. Interassay variation of the assays was below 10%.

PMID- 8745142
TI  - Skeletal growth of transgenic mice with elevated levels of circulating insulin
      like growth factor-II.
AB  - Insulin-like growth factor-II (IGF-II) is a major factor produced by skeletal
      tissues. To evaluate endocrine effects of IGF-II on bone growth, we measured
      skeletal dimensions of 12-week-old transgenic mice harbouring fusion genes where
      a human IGF-II cDNA is transcriptionally controlled by rat phospheonolpyruvate
      carboxykinase (PEPCK) promoter sequences. Transgene expression in liver, kidney
      and intestine resulted in circulating IGF-II levels in transgenic mice which were
      2-3-fold higher than in controls. Serum IGF-I concentrations of transgenic mice
      were lower than in controls. Body weight was not influenced by the expression of
      the IGF-II transgene. Only 1 out of 5 measurements taken from the radius was
      significantly affected by the presence of the transgene, while in 60 measurements
      taken from eight other bones there was no difference between transgenic mice and
      controls. Furthermore, serum levels of calcium and phosphate as well as alkaline
      phosphatase activity were not significantly altered in PEPCK-IGF-II transgenic
      mice. Our findings demonstrate that moderately increased levels of circulating
      IGF-II do not cause major changes in skeletal growth and turnover in mice. This
      may be due to a lack of activity of circulating IGF-II on bone growth or to
      physiological consequences of elevated IGF-II, like a reduction of circulating
      IGF-I or an increase in IGF binding proteins.

PMID- 8745143
TI  - Immunohistochemical localization of insulin-like growth factor-II in the
      perinatal rat gonad.
AB  - To clarify the participation of insulin-like growth factor type-II (IGF-II) in
      rat gonadal differentiation, immunohistochemical localization of IGF-II was
      chronologically studied in Sprague-Dawley rat gonads from gestational day (GD) 13
      to postnatal day (PD) 21 by using avidin-biotin complex technique. In male
      gonads, most cells were negative to IGF-II immunostaining during the perinatal
      period. Only Leydig/interstitial cells expressed positive reactivity from GD 21
      to PD 11: the intensity of staining and the number of positive cells were
      gradually increased until PD 11. In female gonads, almost all cells showed
      negative immunoreactivity. Mesonephric tubules in both sexes exhibited slight or
      moderate reactivity on GD 13. These results indicate that IGF-II is likely to
      participate in the regression of fetal-type Leydig cells and/or the proliferation
      of adult-type Leydig cells around birth, and in the development of mesonephric
      tubules in the initial stage of gonadal differentiation.

PMID- 8745144
TI  - Characterization of the insulin-like growth factor (IGF) axis in the serum of
      maternal and fetal macaques (Macaca mulatta and Macaca fascicularis).
AB  - The insulin-like growth factors (IGFs) are key effectors of fetal growth and
      development which are modulated by serum carrier proteins (IGF binding proteins
      [IGFBPs]). Studies were performed to evaluate the developmental profile of IGFs
      and IGFBPs in the macaque, an important nonhuman primate model for human
      development and disease. IGF-I, IGF-II, and IGFBP-3 were studied in the rhesus
      (Macaca mulatta) and long-tailed (Macaca fascicularis) monkey fetus and dam
      during the second and third trimesters of pregnancy. Serial fetal blood samples
      were collected by cardiocentesis every 10 days from gestational day (GD) 90-160,
      and at 1 month postnatal age; maternal blood samples were collected at similar
      timepoints. Results indicated that maternal sera IGF-I and IGF-II did not change
      significantly whereas fetal concentrations of serum IGF-I and IGF-II increased
      approximately two-fold during the second to the third trimesters. No significant
      differences were detected between the two species. Western-ligand blot analysis
      revealed predominant IGFBPs of 45-40 (IGFBP-3) and 28 kDa (IGFBP-1) in both the
      maternal and fetal compartments, and Western-immunoblot analysis using a specific
      antisera against IGFBP-3 indicated 45-40 and 28 kDa immunoreactive forms. Thus,
      although IGF-I, IGF-II, and IGFBP-3 remained relatively unaffected in maternal
      sera during this period of gestation, fetal concentrations of IGF-I, IGF-II, and
      IGFBP-3 increased in a developmental profile similar to the human fetus.

PMID- 8745145
TI  - Regulation of hepatic mRNA levels for the growth hormone receptor in rats with
      altered thyroid status.
AB  - Changes in thyroid status have a major effect on the GH/IGF-I axis. In the rat,
      there is a single gene for the growth hormone receptor (GHR), that is transcribed
      into two different sized mRNA transcripts following alternative splicing, one
      transcript codes for the GHR (4.0-4.5 kb) and the other growth hormone binding
      protein (GHBP) (1.2-1.3 kb). We have studied the regulation of hepatic GHR gene
      expression by thyroid hormones in male Wistar rats rendered hypothyroid (n = 6)
      and hyperthyroid (n = 6) compared to controls (n = 6). By northern blot analysis,
      two transcripts with an estimated size of 4.2 and 1.2 kb, respectively, were
      detected in all groups. Hyperthyroidism was associated with a significant
      increase in the 4.2 kb transcript compared to hypothyroidism (P < 0.05), but no
      changes were observed in the 1.2 kb transcript. Thus, our results suggest that in
      the rat hyperthyroidism is associated with either increased hepatic gene
      transcription or decreased clearance of the 4.2 kb transcript for the GHR
      compared with hypothyroidism.

PMID- 8745146
TI  - Iodide-dependent regulation of thyroid follicular cell proliferation: a mediating
      role of autocrine insulin-like growth factor-I.
AB  - An inhibitory action of intracellular iodide on the autocrine production of
      insulin-like growth factor-I (IGF-I) by thyroid follicular cells (TFCs) in vitro
      has been investigated as a possible mechanism underlying the iodide-dependent
      control of TFC proliferation. IGF-I release from primary monolayer cultures of
      porcine TFCs increased 5-fold between 24 and 168 h of incubation. Confirmation of
      a mediating role of IGF-I in TFC proliferation was obtained by exposing TFCs to
      an immunoadsorbing IGF-I antiserum, which led to a significant (P < 0.05) decline
      in [methyl-3H]thymidine incorporation, relative to TFCs exposed to preimmune
      serum. Exposure of TFCs to sodium iodide (NaI; 0.1-100 mumol/l) led to an
      attenuation of the IGF-I content of the cell-conditioned medium. This was
      accompanied by a reduction in [methyl-3H]thymidine incorporation that was
      affected by IGF-I immunoneutralization. The inhibitory effect of NaI on IGF-I
      production and [methyl-3H]thymidine incorporation were reversed by the thionamide
      compound methimazole (MMI; 1 mmol/l), exposure to which also led to significant
      (P < 0.001) increases above control values. However, a residual suppressive
      effect of NaI on [methyl-3H]thymidine incorporation suggested that certain of the
      TFC growth-attenuating effects of iodide may not be dependent upon
      organification. While providing evidence, therefore, for a direct relationship
      between iodide exposure, suppression of autocrine IGF-I production and a
      regulation of TFC proliferation, the present studies also suggest that
      suppression of TFC proliferation by iodide may be partially mediated by MMI
      insensitive events.

PMID- 8745147
TI  - Effects of IGF-I, alone and in combination with 17 beta-oestradiol, on bone
      remodelling parameters in ovariectomised rats.
AB  - We studied the effects of recombinant human IGF-I (250 micrograms/day) and/or 17
      beta-oestradiol (E2; 5 or 50 micrograms/kg/day), s.c., for 28 days, on plasma IGF
      I and 1,25-(OH)2 vitamin D3 concentrations and on biochemical indices of bone
      remodelling (plasma osteocalcin, urinary pyridinolines) in 3 month-old rats that
      had been ovariectomised (OVX) 6 weeks before. Ten weeks after ovariectomy, plasma
      1,25-(OH)2D3 was increased, but IGF-I and bone remodelling indices were within
      the normal range. RhIGF-I administration to OVX rats increased both IGF-I and
      1,25-(OH)2D3 concentrations, as well as plasma osteocalcin and urinary
      pyridinoline excretion. By contrast, E2 decreased plasma IGF-I and 1,25-(OH)2D3
      and the markers of bone remodelling. The combination of rhIGF-I and E2 resulted
      in intermediate effects. Multiple regression analysis showed that IGF-I
      correlated with plasma osteocalcin, and also with the urinary excretion of
      pyridinolines. The data shows that rhIGF-I stimulates bone remodelling in growing
      OVX rats, and that circulating IGF-I is a determinant of bone remodelling in
      vivo.

PMID- 8745148
TI  - Expression of aberrantly spliced growth hormone receptor mRNA in the sex-linked
      dwarf chicken, Gifu 20.
AB  - The structure and expression of the growth hormone receptor (GHR) gene have been
      studied in a sex-linked dwarf (SLD) chicken strain, Gifu 20. No gross structural
      change in the receptor gene was observed by Southern blot analysis, however, a
      transcript of 5.5 killobases (kb), which was approximately 1 kb larger than the
      usual chicken full length-GHR mRNA was detected in the dwarf chicken by Northern
      blot analysis. GHR cDNA was obtained from dwarf chicken liver RNA by reverse
      transcription-polymerase chain reaction, and nucleotide sequence analysis
      revealed that it contained an intron sequence of the GHR gene. The unspliced
      intron showed a single point mutation at the donor site from GT to GC, and an
      aberrant stop codon was generated in the extracellular domain-coding region.
      Thus, the mutation resulting in an inappropriate splicing of the GHR gene
      transcript is considered to be the cause of this dwarf chicken.

PMID- 8745149
TI  - Mechanisms of hyperkalemia caused by nafamostat mesilate.
AB  - 1. Nafamostat mesilate (NM) is a novel serine-protease inhibitor used for the
      treatment of acute pancreatitis and disseminated intravascular coagulation.
      Recently, NM has been reported to cause hyperkalemia due to reduced urinary
      excretion of potassium (K). 2. This review briefly summarizes the roles of the
      cortical collecting duct (CCD) in the renal K excretion. 3. In vitro
      microperfusion technique was applied to examine whether NM, and its two
      metabolites, p-guanidinobenzoic acid (PGBA) and 6-amidino-2-naphthol, directly
      act on the CCD. 4. It was demonstrated that these compounds act mainly on the
      apical membrane of the collecting duct cell in the CCD and inhibit the amiloride
      sensitive sodium (Na) conductance, resulting in an inhibition of K secretion.
      PGBA had the most potent action. 5. This direct action of these two metabolites,
      rather than NM, could contribute to the NM-induced hyperkalemia.

PMID- 8745150
TI  - Serotonin binding proteins "SBP": target proteins and tool for in vitro
      neurotoxicity studies.
AB  - 1. Serotonin binding proteins (SBP, 45 and 56 kDa) were initially believed to
      store, transport and/or protect serotonin in serotonergic neurons and, later, to
      play a catecholamine "housekeeping" function as well. 2. Monoamines do not form
      coordination bonds with a preformed iron-SBP complex, as initially believed.
      Instead, metals oxidise the monoamines either directly (manganese, copper) or via
      oxygen free radical formation (iron) and the oxidation products bind covalently
      to SBP. 3. SBP are not involved in the housekeeping of monoamines and actin is
      likely to represent the 45 kDa form. 4. SBP are targets of catecholamine and
      serotonin-related neurotoxins and monoamine-SBP binding could represent an in
      vitro model for neurotoxicity.

PMID- 8745151
TI  - Mitogenic signal transduction in human breast cancer cells.
AB  - 1. Signal transduction pathways activated during growth of human breast cancer
      cells in tissue culture are reviewed. 2. Steroid hormones and growth factors
      stimulate similar mitogenic pathways and frequently modulate each other's
      activity. 3. A response common to estrogen, progestins and most polypeptide
      mitogens is induction of the nuclear transcription factors myc, fos and jun in
      early G1 phase of the cell cycle. 4. Some growth factors also stimulate cyclin
      D1, a regulatory protein responsible for the activation of cell cycle-dependent
      kinases in G1. 5. In addition, insulin, IGF-I and EGF activate tyrosine kinase
      receptors. 6. Several tyrosine phosphorylated proteins occur in human breast
      cancer cells, and include the EGF and estrogen receptors. 7. Cyclic AMP plays a
      critical role in breast cancer cell proliferation through the activation of
      protein kinase A, and it also modulates the activity of estrogen and progesterone
      receptors. 8. EGF is the only breast cell mitogen known to raise intracellular
      free calcium levels. 9. Calcium may play a dual role in breast cancer cell
      proliferation, activating both calmodulin-dependent processes and regulating cell
      membrane potential through the activation of potassium channels. 10. Potassium
      channel activity and cell proliferation are linked in breast cancer cells, the
      cell membrane potential shifting between a depolarized state in G1/G0 cells and a
      hyperpolarized state during S phase. 11. Activation of an ATP-sensitive potassium
      channel is required for breast cancer cells to undergo the G1/G0-S transition.

PMID- 8745152
TI  - Role of calcium in brain aging.
AB  - 1. Calcium is a universal messenger of extracellular signals in a great variety
      of cells; it regulates several neuronal functions, such as neurotransmitter
      synthesis and release, neuronal excitability, phosphorylation and so on. Calcium
      is also involved in long-term processes, like memory. 2. Recent studies
      demonstrated that brain aging is characterized by alterations in neuronal
      function due to the changes in calcium homeostasis. This occurs for various
      reasons, such as changes in calcium channels, decrease of ion binding to specific
      proteins and changes in the mechanisms involved in its sequestration and
      extrusion from neuronal cell. 3. Moreover, it has been shown that high levels of
      glucocorticoids are neurotoxic, because they alter calcium homeostasis on
      hypothalamic neurons by increasing calcium voltage-dependent flow, especially in
      aged neurons. 4. New information about the role of calcium in brain aging could
      derive from the expansion of new imaging techniques, such as positron emission
      tomography, single photon emission tomography and nuclear magnetic resonance,
      which allow in vivo quantitative measurements of functional parameters and their
      comparison with behavioural data.

PMID- 8745153
TI  - Conditions that lithium inhibits or potentiates vasopressin V1-receptor-mediated
      platelet aggregation and [Ca++]i mobilization.
AB  - 1. Besides clinical use, there are many explanations for the mechanism of action
      of lithium. Although it is shown that lithium may reduce the supply of inositol
      that is required to sustain phosphoinositide synthesis, evidence exists
      concerning the potentiating effect of lithium on this pathway. We therefore
      decided to evaluate conditions in which lithium inhibits or potentiates platelet
      aggregation and calcium response induced by vasopressin. 2. Platelet aggregation
      was measured by the photometric method, and changes in intracellular free calcium
      were measured using fura-2/AM. 3. We show an inhibitory action of neomycin on
      vasopressin-induced platelet aggregation. Lithium, according to the preincubation
      time, could both potentiate or inhibit platelet aggregation and calcium responses
      induced by vasopressin. The inhibitory effect of lithium on platelet aggregation
      is dependent on concentrations of both lithium and vasopressin and also the
      presence of indomethacin, for example, in the absence of indomethacin there was
      no clear inhibitory action of lithium on vasopressin-induced platelet
      aggregation. 4. These results show the importance of arachidonate metabolites
      concerning lithium effects on platelet V1-receptor signaling. In conclusion,
      because the arachidonate metabolites are responsible for the release of other
      active substances from platelets' granules, the aggregatory responses in the
      absence of indomethacin may be amplified, and this subsequently may change the
      net inhibitory action of lithium.

PMID- 8745154
TI  - Effect of selenium on ischemic and reperfusion injury in isolated guinea pig
      lungs.
AB  - 1. An experimental comparative study on isolated guinea pig lungs was carried out
      to determine the effect of selenium added to pulmoplegic solution on ischemic
      lung preservation. 2. Two different types of solutions (Eurocollins in control
      group and Eurocollins + selenium 10(-3) M in experimental group) were infused
      before 3 hr of normothermic ischemia. 3. Tissue malone dialdehyde (MDA) and
      tissue glutathione (GSH) levels were assessed before the ischemic period, after
      the ischemia and at the end of reperfusion. Electron microscopic changes were
      also studied at the end of reperfusion to compare the cellular injury between the
      groups. 4. Addition of selenium before the ischemic period relatively decreased
      tissue MDA levels after reperfusion but did not alter tissue GSH levels.

PMID- 8745155
TI  - Protein kinase C isozymes in prostatic epithelial cells from normal, diabetic and
      insulin-treated diabetic rats.
AB  - 1. Immunoblot experiments in rat prostatic epithelium using a non-selective
      antibody against protein kinase C (PKC) allowed to detect three PKC subspecies of
      87.5, 55.5 and 34.6 kDa that showed higher, similar and lower immunoreactivity in
      the membrane than in the cytosolic compartment, respectively. 2. Specific
      monoclonal antisera revealed that the PKC-gamma isozyme is not expressed in the
      rat prostatic epithelium, whereas the PKC-beta isozyme was noted only in the
      cytosolic fraction showing an apparent molecular weight of 75.5 kDa. 3. Induction
      of diabetes by streptozotocin led to modifications in the expression of PKC
      isozymes so that the immunoreactivities of the 87.5- and 55.5-kDa PKC forms
      decreased in both cytosolic and membrane subcellular fractions to different
      extents. 4. The most important decrease was that of the 55.5-kDa PKC form in
      cytosol that returned to control values by insulin therapy, whereas PKC-beta
      suffered also some decrease in diabetes and increased again with insulin
      treatment.

PMID- 8745156
TI  - Long-term nifedipine treatment reduces calcium overload in isolated reperfused
      hearts of diabetic rats.
AB  - 1. Streptozotocin-induced diabetic rats showed poor post-ischemic recovery in
      isolated working rat hearts. 2. Diabetic rats showed myocardial Na+ accumulation
      after ischemia, and Ca2+ level and water content elevation after reperfusion. 3.
      A 6-wk nifedipine treatment improved post-ischemic recovery of cardiac parameters
      and prevented myocardial Na+ accumulation after ischemia and myocardial Ca2+
      level and water content elevation after reperfusion of diabetic rats. 4. Results
      suggest that nifedipine treatment improves cardiac dysfunction in the reperfused
      ischemic hearts of diabetic rats through normalization of the Na+-Ca2+ imbalance
      and water content.

PMID- 8745157
TI  - No evidence for dopamine-induced relaxation in isolated human mesenteric arterial
      strips from elderly patients.
AB  - 1. We investigate the effects of dopamine in isolated mesenteric artery from
      elderly patients. 2. Noradrenaline (10(-11) to 10(-4) M) and dopamine (2.7 x 10(
      6) to 1.4 x 10(-3) M) induced a concentration-dependent contraction that was
      antagonized by prazosin. Fenoldopam (10(-8) to 10(-4) M) and clonidine (10(-9) to
      10(-4) M) did not produce any contractile effects. 3. Potassium chloride (80 mM)
      produced a well-maintained plateau contraction and dopamine-induced contraction
      in these conditions, which was decreased by prazosin (10(-8) M). Neither
      fenoldopam nor isoprenaline (10(-10) to 10(-5) M) modified the well-maintained
      plateau. 4. Our results suggest that post-synaptic dopamine receptors are not
      present in this preparation but alpha1-adrenoceptors are present.

PMID- 8745158
TI  - Effect of the intraperitoneal administration of salmon-calcitonin on the "in
      vitro" actions of opioid agonists.
AB  - 1. The interaction of intraperitoneal administration of salmon-calcitonin with
      opioids was studied. The study was carried out using guinea pig ileum (mu and
      kappa-opioid receptors), rabbit vas deferens (kappa-opioid receptors) and mouse
      vas deferens (delta-opioid receptors), and selective mu, delta and kappa agonists
      were used in the pertinent tissues. 2. The treatment with salmon-calcitonin
      increased, in a dose-dependent manner, the effect of U-50,488H in guinea pig
      ileum and rabbit vas deferens and the effects of [D-Pen2, D-Pen5] enkephalin in
      mouse vas deferens. 3. The treatment with analgesic doses of salmon-calcitonin
      enhances the in vitro effects of kappa- and delta-opioid agonists. The increase
      of the effectiveness of the opioid agonists may be one of the mechanisms involved
      on the analgesia induced by salmon-calcitonin.

PMID- 8745159
TI  - Further mapping of the Achatina giant neurone types sensitive to the neuroactive
      peptides isolated from invertebrates.
AB  - 1. The effects of the 10 synthetic neuroactive peptides originally isolated from
      invertebrates, applied locally to the neurone tested by the brief pneumatic
      pressure ejection on the identifiable neurone types of Achatina fulica Ferussac
      were examined. 2. Achatin-1 (Gly-D-Phe-Ala-Asp), an Achatina endogenous
      tetrapeptide having a D-phenylalanine residue, ejected locally, showed the
      depolarizing effects on nearly half of the number of neurone types tested. 3.
      ACEP-1 (Ser-Gly-Gln-Ser-Trp-Arg-Pro-Gln-Gly-Arg-Phe-NH2), isolated originally
      from Achatina atria, and pedal peptide (Pro-Leu-Asp-Ser-Val-Tyr-Gly-Thr-His-Gly
      Met-Ser-Gly-Phe-Ala) and buccalin (Gly-Met-Asp-Ser-Leu-Ala-Phe-Ser-Gly-Gly-Leu
      NH2), found in Aplysia neurones, showed excitatory effects on some Achatina
      neurone types. 4. Myomodulin (Pro-Met-Ser-Met-Leu-Arg-Leu-NH2), found in Aplysia
      neurones, produced a hyperpolarization on nearly half of the number of Achatina
      neurone types tested. The two FMRFamide-like peptides, <EDPFLRFamide (<Glu-Asp
      Pro-Phe-Leu-Arg-Phe-NH2), isolated from Helix heart, and AF1 (Lys-Asn-Glu-Phe-Ile
      Arg-Phe-NH2), from Ascaris head, also showed hyperpolarizing effects on more than
      half of the number of Achatina neurone types. 5. SALMFamide 1 (Gly-Phe-Asn-Ser
      Ala-Leu-Met-Phe-NH2), isolated from Asterias nervous system, CCAP (Pro-Phe-Cys
      Asn-Ala-Phe-Thr-Gly-Cys-NH2), from Carcinus pericardial organ, and corazonin
      (<Glu-Thr-Phe-Gln-Tyr-Ser-Arg-Gly-Trp-Thr-Asn-NH2), from Periplaneta cardiac
      corpus, had no effect on Achatina neurones.

PMID- 8745160
TI  - Central and peripheral 5-HT receptors in the leech (Hirudo medicinalis)
      redefined.
AB  - 1. 5-Hydroxytryptamine (5-HT) receptors in the Retzius neurones (R cells) and
      longitudinal body wall muscle strips of the leech H. medicinalis were studied
      using a range of selective agonists developed for mammalian receptors. 2. All
      agonists induced hyperpolarisation of R cells: the order of their potency was 5
      HT > 5-CT > 2-Me 5HT > alpha-Me-5-HT > > CGS-12066B = 5MeOT > PAPP > Buspirone.
      This receptor is most like a mammalian 5-HT1C/2 receptor. 3. 5-HT induces
      relaxation of body wall strips, preceded at higher doses by contraction or an
      increase in spontaneous contractions. The relaxing effect was best mimicked by 5
      CT and alpha-Me-5-HT, suggesting a 5-HT1C/2 receptor. The contractile effect was
      best mimicked by 5-MeOT suggesting a 5-HT4-like receptor. The overall potency of
      agonists on the body wall muscle was 5-MeOT > 5-CT > 5-HT > alpha-Me-5-HT > 2-Me
      5-HT > PAPP > Buspirone > > CGS-12066B. 4. Results suggest that either the sites
      of 5-HT action possess several different receptors or the receptors themselves
      are more complex with multiple properties.

PMID- 8745161
TI  - Properties of slow early potassium current in neurons of snail Helix pomatia.
AB  - 1. In isolated neurons of visceral ganglia of snail Helix pomatia a slow early
      outward current (IA) was studied using a two-microelectrode voltage clamp
      technique. 2. The time of activation and inactivation of IAS at -40 mV were 90
      120 msec and 3-5 sec respectively. The removal of inactivation at -120 mV took 2
      5 min. 3. The reversal potential of the IAS was about -80 mV in normal saline and
      was sensitive to the external potassium concentration, changing about 35 mV per
      fivefold change in potassium over the range from 4 to 20 mM. The results suggest
      that IA were due to K+. 4. The IA persisted in Ca2+ -free medium and in the
      presence of Ca2+ -channels blockers, e.g., Cd2+. 5. The IA were blocked by 1-10
      microM extracellular 4-aminopyridine, 1 mM of tetraethylammonium ions, 1 mM of
      Ba2+, but one was resistant to 1 mM Cs+. 6. 4-aminopyridine had a dual effect on
      the IA. It blocked the normal current, and then appeared to increase the
      inactivated currents.

PMID- 8745162
TI  - The actions of nickel on membrane currents activated by hyperpolarisation in
      single cells from the rabbit atrioventricular node.
AB  - 1. The atrioventricular node (AVN) is vital for cardiac function as it normally
      provides the only conduction route for the cardiac impulse from atria to
      ventricles and can act as a pacemaker for the ventricles if the sinoatrial node
      (SAN) fails. We have shown previously that whilst 80-90% of AVN myocytes do not
      possess If (we have termed these type 1 cells), a small proportion (10-20%) of
      AVN cells (type 2) do exhibit If. 2. The present study describes the effects of
      the divalent cation nickel (Ni) on membrane currents activated by hyperpolarising
      voltage clamps from -40/mV in type 1 and type 2 cells at 35 degrees C, using the
      whole cell patch clamp technique. In type 2 cells 5 mM Ni enhanced the amplitude
      of If. At -120 mV the mean Ni-activated If was -1.85 +/- 0.28 pA/pF (mean +/-
      SEM; n = 5). Ni significantly enhanced If at -70 mV and at all potentials
      negative to this (p < 0.05 at -70, -80, -90 and -110 mV; 0.05 < p < 0.1 at -100
      mV; p < 0.005 at -120 mV). 3. In type 1 cells, which exhibit a small time
      independent inward current on hyperpolarisation there was no activation of If by
      Ni (p > 0.1 at all potentials between -40 mV and -120 mV). 4. In type 1 cells 5
      mM Ni significantly reduced the time-independent inward current activated by a
      hyperpolarising pulse to -120 mV (p < 0.02) and had a smaller effect at -110 and 
      100 mV (0.05 < p < 0.1 at these potentials). With pulses to less negative
      potentials there was no significant alteration of the time-independent current.
      5. An additional observation was that the fast sodium current activated on
      repolarisation of the membrane potential to -40 mV after a hyperpolarising
      voltage clamp appeared to be blocked by Ni. However, this apparent blockade
      reflected a positive shift in the activation threshold for INa, since a
      repolarising step to -30 mV could still elicit INa. 6. Ni is known to block
      sarcolemmal Na/Ca exchange in cardiac cells, and one possible mechanism for the
      enhancement of If by Ni in type 2 cells is increased intracellular Ca via Na/Ca
      exchange blockade increasing If. The reduction in end pulse current in type 1
      cells is also consistent with Na/Ca exchange current blockade. A second
      possibility of the enhanced If in type 2 cells with Ni is a positive shift of the
      activation curve for If in the presence of an increased concentration of external
      divalent cations.

PMID- 8745163
TI  - Effects of lithium and myoinositol on the rat bisected vas deferens.
AB  - 1. The effects of lithium (Li+) on the concentration-response curves (CRC) to
      norepinephrine (NE) and acetylcholine (Ach) on the bisected rat vas deferens
      (RVD) were investigated, as well as its action on the neuronal uptake of [3H] NE.
      2. Li+ did not affect the 50% effective concentration (EC50) of NE and Ach in the
      epididymal (EP) portion of the RVD. 3. Li+ caused a significant increase of the
      EC50 to NE and Ach in the prostatic (PP) portion of the RVD. This shift to the
      right of the CRC to NE was prevented by the presence of myoinositol. 4.
      Incubation of the PP of the RVD with Li+, increased the neuronal uptake of NE.
      The simultaneous incubation with myoinositol prevented this increase. 5. After
      the pre-treatment of the rats with 6-hydroxydopamine (6-OHDA), or in the presence
      of cocaine, Li+ failed to desensitize the PP of the RVD to NE. 6. These results
      suggest that the effect of Li+ on the PP of the RVD occurs mainly at the pre
      synaptic level and may be related to the increase of neuronal uptake and to the
      interference of Li+ on phosphatidylinositol hydrolysis.

PMID- 8745164
TI  - Actions of perezone on rat smooth muscle.
AB  - 1. Perezone (PZN) on the in vitro intestinal smooth muscle of the rat relaxes the
      basal tonus of the smooth muscle, interrupts spontaneous activity and also blocks
      the contractile response induced by ACh, K+, and Ba2+; these actions are dose
      dependent. 2. Although in presence of small doses of PZN, the isometric
      contractile response to ACh was increased. 3. In calcium free intestinal smooth
      muscle preparation, the addition of PZN in low dose before Ca2+ increased the
      contractile effect of added calcium to the bath, but in presence of high doses of
      PZN the response to calcium was depressed. 4. PZN in calcium free preparations
      antagonized the contraction caused by adding barium. 5. These findings suggested
      that with small doses of PZN more availability of intracellular calcium free
      exist and/or an increase in excitability and/or an inhibition of AChase could
      coexist. 6. The responses of the intestine to high doses of PZN were possibly in
      part by blocking calcium entry. 7. The smooth muscle responses to PZN suggest
      that it has a membranal effect and/or an action on the internal calcium stores
      possibly increasing the intracellular calcium concentration. It is likely to be
      the expression of an increase in the intracellular calcium concentration above
      the levels normally reached that would be responsible for uncoupling of the
      smooth muscle, which would occur if the [Ca2+]i rises excessively.

PMID- 8745165
TI  - H-7, a protein kinase C inhibitor, inhibits spontaneous tone and spasmogenic
      responses in normal and sensitized guinea pig trachea.
AB  - 1. H-7, a protein kinase C inhibitor, fully inhibited the spontaneous and
      stimulated (KCl 20 mM or histamine 0.5 mM) tone of trachea from normal and
      sensitized guinea pig. 2. H-7 depressed the concentration-contraction curves to
      KCl, histamine or 5-hydroxytryptamine in epithelium-denuded, indomethacin
      treated, trachea from normal and sensitized guinea pigs while responses to CaCl2
      (in Ca2+ -free, K+ -depolarized tissues) and acetylcholine were not affected. 3.
      H-7 (100 microM did not depress Ca2+ (20 microM-induced contraction of Triton X
      100 skinned trachea. 4. These results suggest the involvement of PKC in the
      maintenance of spontaneous tone and spasmogenic responses of guinea pig trachea.

PMID- 8745166
TI  - Metabolism of simple quinones in guinea pig and rat cardiac tissue.
AB  - 1. The metabolism of the benzoquinone 2,5-dimethylbenzoquinone and of the
      naphthoquinone 2,3-dimethoxy-1,4-naphthoquinone was studied in subcellular
      fractions isolated from cardiac tissue of guinea pig and rat. 2. In both species
      the benzoquinone was mainly metabolized through the mitochondrial NADH-ubiquinone
      oxidoreductase, whereas the naphthoquinone was metabolized to approximately equal
      extents by mitochondrial reductase and by soluble DT-diaphorase. 3. Guinea pig
      heart metabolized 3 times more naphthoquinone than rat heart. 4. As a consequence
      of quinone metabolism, marked amounts of O2- center dot - were generated;
      naphthoquinone-induced O2- center dot - generation was about 4-fold higher in
      guinea pig than in rat heart.

PMID- 8745167
TI  - Effects of tandospirone on second messenger systems and neurotransmitter release
      in the rat brain.
AB  - 1. We studied the effects of tandospirone, a novel serotonin (5-HT)1A receptor
      related anxiolytic, on the intracellular second messenger systems and
      neurotransmitter release. 2. Tandospirone inhibited forskolin-stimulated
      adenylate cyclase activity in rat hippocampal membranes by activation of 5-HT1A
      receptors and had high efficacy comparable to 5-HT1A receptor agonists such as 5
      HT and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 3. Tandospirone
      suppressed carbachol-stimulated phosphatidyl-inositol metabolism (PI response),
      which was shown to be a 5-HT1A receptor-mediated event. 4. Tandospirone did not
      affect the release of 5-HT, norepinephrine (NE), dopamine (DA) and acetylcholine
      (ACh) from rat brain slice preparations. 5. These findings suggested that
      tandospirone shows high agonistic efficacy on the postsynaptic 5-HT1A receptors
      but does not affect the presynaptic autoreceptors located on nerve endings. The
      modulation of the second messenger system via postsynaptic 5-HT1A receptors might
      be involved in the anxiolytic efficacy of tandospirone.

PMID- 8745168
TI  - Mechanisms of resistance to topoisomerases poisons.
AB  - 1. Drug resistance remains a major obstacle to cancer treatment. Resistance to
      chemotherapy can be intrinsic, characterised by the nonresponsiveness of the
      tumour to the initial treatment. Alternatively, cancers that initially respond to
      chemotherapy can relapse after various times because of acquired resistance. 2.
      Resistance to drugs used as single agents is generally accompanied by the
      development of resistance to other drugs that can be structurally and
      functionally different. 3. Among the drugs commonly used in cancer treatment
      there are compounds that have been shown to inhibit DNA topoisomerases (Topos).
      These critical enzymes regulate the topological conformation of the DNA and
      participate in essential cellular processes. 4. This paper reviews the Topos'
      cellular functions, their catalytic activities and the mechanisms of resistance
      to inhibitors of Topos, with particular attention to the atypical multidrug
      resistance phenotype.

PMID- 8745169
TI  - Effects of adenosine analogues on apomorphine-induced penile erection in rats.
AB  - 1. In the present work, the effect of adenosine agonists and antagonists on
      apomorphine-induced penile erection (PE) has been studied. 2. Subcutaneous (s.c.)
      injection of the nonselective D1/D2 dopamine receptor agonist apomorphine (0.05
      0.5 mg/kg) induced PE in a biphasic manner. The maximum effect was obtained with
      0.1 mg/kg of the drug. The response decreased with increasing doses of
      apomorphine, from 0.1 to 0.5 mg/kg. 3. Intraperitoneal (i.p.) injections of
      adenosine agonists 5'-N-ethylcarboxamidoadenosine (NECA) and N6
      cyclohexyladenosine (CHA) decreased the response of apomorphine. Apomorphine
      induced PE was increased by low doses (25, 50 mg/kg, i.p.) and decreased by high
      doses (75, 100 mg/kg, i.p.) of the adenosine antagonist theophylline,
      respectively. Inhibition of PE induced by NECA and CHA was antagonized by 8-PT
      pretreatment. 4. Intracerebroventricular (i.c.v.) administration of CHA, NECA,
      and theophylline produced the same effects as i.p. injections of these agents on
      PE responses. It is concluded that A-1 and A-2 adenosine receptor activation may
      inhibit PE induced by dopaminergic mechanism(s), which can be prevented by 8-PT
      pretreatment.

PMID- 8745170
TI  - Effect of bupranolol on CGP 12177-induced relaxation and cAMP accumulation in the
      guinea pig taenia caecum.
AB  - 1. The effect of bupranolol on CGP 12177-induced relaxation and cAMP accumulation
      in the guinea pig taenia caecum was examined. 2. The relaxant response to CGP
      12177 was unaffected by propranolol (approximately 10(-6) M), whereas that to CGP
      12177 was antagonized in a concentration-dependent manner by bupranolol; Schild
      plot of the data revealed the pA2 value of 5.61. 3. CGP 12177 significantly
      increased cyclic AMP level in this preparation. Bupranolol (10(-4) M)
      significantly decreased the cyclic AMP level that was elicited by CGP 12177,
      whereas propranolol (10(-5) M) produced no effect. 4. These results suggest that
      bupranolol appears to be an efficient beta3-antagonist in the guinea pig taenia
      caecum and confirm that the response to CGP 12177 is mediated by beta3
      adrenoceptors.

PMID- 8745171
TI  - European survey on cardiac interventions: open-heart surgery, percutaneous
      transluminal coronary angioplasty and cardiac catheterization in 1993. A
      preliminary report by the Institute for Cardiac Survey of the European Academy of
      Sciences and Arts.

PMID- 8745172
TI  - Surgical repair of coarctation of the aorta in neonates: factors affecting early
      mortality and re-coarctation.
AB  - Between October 1979 and January 1993, 85 Chinese neonates in Hong Kong underwent
      surgical repair for coarctation of the aorta. Their mean (s.e.) age and body
      weight at operation was 15.6(8.5) days and 3.06(0.56) kg, respectively. Simple
      coarctation was present in 17 babies, while 36 had additional ventricular septal
      defect and 31 had associated major complex intracardiac lesions. Subclavian flap
      aortoplasty was performed in 56 babies, resection with end-to-end anastomosis in
      18 and aortoplasty with the use of a GORETEX patch in 11. The overall early
      mortality rate was 16.5%. To identify risk factors for early operative mortality,
      various clinical variables, surgical options, associated heart lesions and
      dimensions of the aortic arch at different sites for each patient were reviewed.
      Univariate analysis identified statistically significant differences between the
      survivors and non-survivors for the following factors: preoperative body-weight,
      arterial pH and base excess, serum urea and creatinine levels. Stepwise logistic
      regression further distinguished serum creatinine levels and the period of
      operation as two significant risk factors. Contrary to previous reports, the
      dimensions of the aortic arch and type of surgery did not affect early operative
      mortality. Among the 71 hospital survivors followed for 38.2(38) months, residual
      or recurrent coarctation of the aorta was detected in 12(17%). The different
      surgical operations were not related to the incidence of late complication. The
      size of the distal transverse arch, however, was different (P=0.05) in those who
      did and did not develop aortic sequela. Successful balloon angioplasty was
      subsequently performed in 11 patients. In an era of echocardiography with
      prenatal diagnosis and therapeutic catheterization, early recognition of the
      disease with prompt prostaglandin infusion should prevent collapse of the baby,
      thus avoiding renal impairment and sever metabolic acidosis. Balloon angioplasty
      would offer a simple effective treatment of patients who developed aortic re
      coarctation.

PMID- 8745173
TI  - Surgical treatment for acute native aortic valvular infective endocarditis: long
      term follow-up.
AB  - During the period 1970-1993, 116 patients (63 men, 53 women) with native aortic
      valvular infective endocarditis were treated surgically. The mean age was 37
      years. The main causative organisms were streptococci and staphylococci.
      Indication for surgery was cardiac failure (70 cases), uncontrolled sepsis (30),
      peripheral emboli (11) and overwhelming destruction of the aortic valve (five).
      Hospital and late mortality rates were 8% and 11% respectively. Patients who died
      in hospital and those who presented a paravalvular leakage had a ring abscess
      associated with aortic wall destruction. Among 34 patients screened for cerebral
      septic emboli the condition was confirmed in 15, of whom six were symptom-free.
      Thus, it is believed that in the presence of root abscess, surgery should be
      undertaken promptly, regardless of the cardiac status. It is confirmed that
      cerebral septic emboli should be systematically screened for in the presence of
      any infective endocarditis.

PMID- 8745174
TI  - Left ventricular function on exercise after surgical treatment of small aortic
      annuli.
AB  - To evaluate left ventricular function during exercise after aortic annular
      enlargement 15 patients with either aortic (group I, n = 8) or aortomitral (group
      II, n = 7) annuloplasty for small aortic annuli and eight patients (group III)
      with standard valve replacement for aortic stenosis without small aortic annuli
      received gated cardiac pool imagining by technetium-99m-labelled red blood cells
      at rest and during exercise at a mean of 23 months after operation. Left
      ventricular ejection fraction, preload requitable stroke work and stroke power
      index (preload requitable stroke work/systolic ejection period) were measured.
      Compared with resting values, left ventricular performance and stroke work rate
      on exercise after aortic annular enlargements increased significantly, as did
      those after standard aortic valve replacement. These results suggest that aortic
      annular enlargement can be indicated for surgical treatment of valvular heart
      diseases associated with small aortic annuli.

PMID- 8745175
TI  - Does interruption of normothermic cardioplegia have adverse effects on
      myocardium? A retrospective and prospective clinical evaluation.
AB  - A total of 154 patients who underwent isolated coronary revascularization
      (coronary artery bypass grafting) using retrograde, near-continuous, warm
      cardioplegia for myocardial protection, were arbitrarily divided into three
      groups according to the cumulative cardioplegic interruption (i.e. the sum total
      of all the short cardioplegic interruption periods, expressed as a percentage of
      the cardiac arrest period). Group 1 (39 patients) had < 20% interruption
      (mean(s.e.m.) 12.5(0.01)%), group 2 (82 patients) had 20-39% interruption
      (mean(s.e.m.) 30.1(0.01)%) and group 3 (33 patients) had > 40% interruption
      (mean(s.e.m.) 45.4(0.01%). The three groups were comparable except for longer
      clamp time in group 3 and a lower cardiac index in group 1. The mean number and
      duration of cardioplegic interruptions and reperfusions and multiple clinical
      outcomes were recorded. Clinical outcomes (Q) wave perioperative infraction, use
      of an intra-aortic balloon pump, mortality, and length of stay in the intensive
      care unit and hospital) were the same in all groups despite significant
      differences in percent, number and duration of interruption and reperfusion as
      well as cardiac arrest. The only significant differences found were in the level
      of creatine kinase-MB (CK-MB) and use of inotropes after surgery, both being
      higher in group 1 than in groups 2 and 3 (which is the opposite of what would be
      expected). Intraoperative hemodynamic (cardiac index and left ventricular
      ejection fraction) and metabolic evaluations (CK-MB, lactate production and
      oxygen extraction) in 22 additional patients who underwent coronary artery bypass
      grafting showed no significant differences between two groups having < 30% versus
      > 30% cumulative cardioplegic interruption. It is concluded that warm
      cardioplegic interruption as used clinically has no adverse effects on the
      myocardium in patients undergoing coronary revascularization. Warm retrograde
      near-continuous blood cardioplegia is an effective method of myocardial
      protection.

PMID- 8745176
TI  - Cardiac myxomas: surgical treatment and long-term results.
AB  - Twenty-six patients have undergone a resection of a cardiac myxoma since 1977.
      There were five males and 21 females, of age range 14-81 years (mean 50 years).
      Symptoms included congestive heart failure, emboli, palpitations and syncope. The
      tumours were located in the left atrium (21 patients), right atrium (four) and
      right ventricle (one). The hospital mortality rate was 3.8%. Late outcome was
      known for 24 of 25 (96%) patients. The total follow-up is now 2116 months (mean
      88 (range 2-204) months per patient). One patient (4%) died of colonic malignancy
      4 years after surgery. Long-term results were satisfactory. Echocardiographic
      information supporting the absence of recurrence was known for all 23 patients,
      evaluated at an average of 80 (range 2-196) months postoperatively. Surgical
      resection is the correct treatment for cardiac myxoma and is imperative following
      the diagnosis.

PMID- 8745177
TI  - Intraoperative detection of unsuspected distal coronary obstruction by thermal
      coronary angiography.
AB  - Intraoperative assessment of graft patency and completeness of revascularization
      can increase the success of coronary artery bypass grafting. A 56-year-old man
      underwent a quadruple bypass operation. Flow in the graft to the anterior
      descending artery was verified after completion of the distal anastomosis using a
      Doppler flow detector. Visualization of the native artery by thermal coronary
      angiography demonstrated that the flow passed into the second diagonal branch and
      not into the distal anterior descending artery, which had an unsuspected
      obstruction just distal to the anastomosis. The obstruction was dilated. Patency
      was verified with cold solution, and flow of warm blood to the entire artery was
      accomplished. This case demonstrates how the early (intraoperative) recognition
      of an unsuspected coronary obstruction using an infrared imaging system can
      improve the results of myocardial revascularization and avoid potential
      postoperative complications.

PMID- 8745178
TI  - Myocardial revascularization in a sickle-cell trait patient.
AB  - A 56-year-old man with confirmed sickle-cell trait AS underwent successful triple
      vessel myocardial revascularization with internal mammary artery and vein
      conduits. Variations in routine technique included limitation in hypothermia (32
      degrees C), avoidance of intraoperative autologous salvage, hypoxia, severe
      anemia (< 25% hematocrit), acidosis and postoperative reinfusion of mediastinal
      drainage.

PMID- 8745179
TI  - Acute infectious mitroaortic endocarditis in association with acute aortic
      dissection. Surgical management of an unusual combination of diseases.
AB  - A 58-year-old man with acute mitral and aortic endocarditis suffered an acute
      ascending aortic dissection. The patient had a double valve replacement, combined
      with replacement of the ascending aorta with a Dacron graft and sealing and
      closure of the proximal and distal aortic segments with surgical glue. Six months
      after the operation the patient is doing well with normal function of both valve
      prostheses and aortic vascular graft.

PMID- 8745180
TI  - Splenic infarction from cholesterol embolization following cardiopulmonary
      bypass.
AB  - The authors report a case of symptomatic splenic infarction secondary to
      cholesterol embolization after coronary artery bypass grafting in a 59-year-old
      woman. The patient was treated with urgent splenectomy, which was curative. The
      diagnosis, investigations and management of the condition are discussed.

PMID- 8745181
TI  - Normal and pathological aspects of mass transport across the vascular wall.
AB  - The rapid progress in cardiovascular surgery during the past 10 years has been
      matched by a complementary increase in the understanding of underlying cellular
      and molecular aspects of normal and pathological physiology of blood vessels.
      This review focuses on one aspect of vascular biology, namely the transport of
      macromolecules and water across the vascular wall, with particular attention to
      the role of endothelial permeability, and offers a bridge between the basic
      biological sciences and clinical care.

PMID- 8745182
TI  - Neurogenic thoracic outlet decompression: rationale for sparing the first rib.
AB  - A total of 168 primary supraclavicular decompressions were performed on 146
      patients with neurogenic thoracic outlet syndrome. This report compares the
      results of rib resection (supraclavicular anterior and middle scalenectomy and
      first rib resection) with rib-sparing (supraclavicular anterior and middle
      scalenectomy alone) operations. All patients with cervical ribs were excluded. In
      total, 125 rib resections and 43 rib-sparing procedures were performed between
      1983 and 1992 by a single surgeon. The patients were otherwise comparable in
      symptoms and physical signs. During surgery there was a significantly higher
      proportion of pleural injury associated with rib resection (59%) than with rib
      sparing (40%) procedures. The mean hospital stay was also prolonged by 1 day in
      patients undergoing rib resection (p = 0.005). There was no significant
      difference in early success between the two groups (83% for rib resection, 91%
      for rib sparing) and no difference in those resuming employment (52% and 63%
      respectively). Life-table analysis showed that the two groups have similar long
      term results (69% and 76% at 2 years). The only important factor determining
      clinical outcome in primary supraclavicular thoracic outlet syndrome
      decompression was the duration of symptoms before operation. Some 83% of patients
      with symptoms less that 2 years had a successful result compared with only 68% in
      those with symptoms longer than 2 years (p < 0.05). Spontaneous or post-traumatic
      neurogenic symptoms responded to operation identically. The theoretical benefit
      of first rib resection to relieve mechanical compression of the brachial plexus
      is not evident from this review. Thorough removal of the scalene musculature and
      other myofascial anomalies, preferably through the supraclavicular approach,
      leads to less patient morbidity, shortens hospitalization, and is recommended for
      patients with neurogenic thoracic outlet syndrome requiring operative
      intervention.

PMID- 8745184
TI  - External carotid endarterectomy with internal carotid artery transposition flap
      angioplasty for symptomatic internal carotid artery occlusion.
AB  - The external carotid artery is an important collateral pathway for cerebral
      perfusion when the internal carotid artery is occluded. After internal carotid
      artery occlusion, there is a definite risk of ipsilateral neurological events.
      The authors retrospectively examined their experience with endarterectomy of the
      external carotid artery for symptomatic internal carotid artery occlusion.
      Results based on the authors' experience and on historical data show external
      carotid endarterectomy to be a safe procedure. Obliteration of the cul-de-sac
      appears to be a very important factor in the prevention of reocclusion or
      recurrence of symptoms after external carotid endarterectomy. Use of the internal
      carotid artery stump for patching of the endarterectomized external carotid
      artery is both safe and effective in treating symptomatic internal carotid artery
      occlusion.

PMID- 8745185
TI  - Carotid Dacron patch angioplasty: immediate and long-term results of a
      prospective series.
AB  - The purpose of the present study was to determine the acute clinical results
      associated with the performance of Dacron patch angioplasty during carotid
      endarterectomy, and to define the incidence of residual and recurrent carotid
      stenoses in patched arteries. Some 115 consecutive patients (mean age 68.0 years)
      underwent 119 primary carotid endarterectomy procedures in which the arteriotomy
      was repaired with a Dacron patch. The patients underwent
      duplex/occulopneumoplethysmography evaluation at 6 months after surgery, and
      annually thereafter. There was one (0.8%) operative death and two (1.7%)
      perioperative strokes. There were no immediate postoperative carotid thromboses.
      There were no wound or patch infections acutely, or in long-term follow-up.
      Thirteen patients (11%) were lost to follow-up; hence 106 arteries in 102
      patients were followed for 1-65 (mean 17.8) months, including 66 arteries (62%)
      that have undergone serial OPG/duplex evaluation. The incidence of residual
      stenoses (within 3 months) was 4.5%, and that of recurrent stenoses 4.8%. The
      results of the study show Dacron carotid patch angioplasty to be associated with
      excellent clinical results, with a relatively low incidence of residual/recurrent
      carotid stenoses.

PMID- 8745186
TI  - Carotid-subclavian bypass and the carotid steal phenomenon.
AB  - Twelve patients with patent carotid-subclavian bypass grafts were investigated by
      colour flow duplex imaging to look for a carotid steal. Centre-stream peak
      systolic flow velocities in the common carotid arteries distal to the take-off of
      the bypass graft were equivalent to those in the contralateral common carotid
      artery. On the side of the bypass, common carotid flow proximal to the graft was
      almost double that on the distal side. Steal phenomena were not identified in the
      carotid artery either with the arm at rest or during hyperaemia. However, in two
      instances arm hyperaemia caused reversal of flow in the ipsilateral vertebral
      artery, suggesting the induction of a subclavian steal. The method of centre
      stream peak systolic velocity as an index of flow confirmed that carotid
      subclavian bypass can be safely carried out without depriving the cerebral
      circulation of the normal carotid inflow.

PMID- 8745187
TI  - Carotid endarterectomy: are we under-performing?
AB  - An audit of the number of carotid endarterectomies performed over the last 4
      years was performed in the south western region. For the years 1990, 1991, 1992
      and 1993 the number of cases were 126, 165, 165 and 164 respectively. It is
      estimated for this region that about 600 operations should be carried out per
      annum. This under-performance may reflect a lack of knowledge about the potential
      benefits of surgery.

PMID- 8745188
TI  - Thrombus formation on polytetrafluoroethylene surfaces: the importance of von
      Willebrand factor.
AB  - The importance of von Willebrand factor (vWf) in the formation of platelet-fibrin
      thrombi on expanded polytetrafluoroethylene (ePTFE) surfaces was studied in an in
      vitro system, perfusing non-anticoagulated human blood over ePTFE grafts for 3
      min at varying shear rates (100, 500 and 1500/s shear). Platelet (111In) and
      fibrin (125I) deposition was assessed on ePTFE surfaces in the presence and
      relative absence of vWf, achieved by use of polyclonal anti-vWf antibody (anti
      vWf Ab). A total of 29 perfusions were performed. Increasing shear rate was
      associated with greater platelet deposition in the presence of vWf (p < 0.001).
      This shear-dependent rise in platelet deposition was not observed when vWf was
      blocked by anti-vWf Ab (P < 0.1), confirming the role of vWf in platelet
      deposition at high shear rates. Fibrin deposition increased with increasing shear
      rate in the presence of vWf (P < 0.01). Inhibiting vWf abolished the shear
      dependent increase in fibrin deposition. These data suggest that vWf plays a
      critical role in platelet and fibrin thrombus formation on ePTFE surfaces. These
      effects are particularly important under conditions of high shear rate. These
      mechanisms may lead to the observed pathologic thrombus formation and platelet
      dependent neointimal processes occurring at areas of high shear rate within the
      anastomotic regions of ePTFE grafts.

PMID- 8745189
TI  - Vascular trauma to the lower extremity: the Lebanese war experience.
AB  - The authors' experience with 386 patients who were operated on for vascular
      injuries to the lower extremities is reviewed. Of these, 118 had popliteal
      injuries, 252 had femoral injuries and 16 had tibial injuries. The overall
      mortality rate was 2.33% with no mortality in the popliteal and tibial injuries
      group whereas there were nine deaths in the femoral injuries group. The overall
      amputation rate was 5.95%, with 3.17% amputation rate for the femoral injuries
      group versus 11.86% for the popliteal injuries group and 6.25% for the tibial
      injuries group. Delay in repair (more than 6 h from injury), associated femoral
      fractures and shocked condition on admission led to increased amputation rate.
      Prompt surgical repair, arterial as well as venous repair for popliteal and
      femoral injuries especially if femoral fracture is present, external skeletal
      fixation and/or traction, and fasciotomy when necessary led to improved limb
      salvage.

PMID- 8745190
TI  - Non-invasive impedance analysis: a new non-invasive test for graft surveillance.
AB  - Detection of failing grafts with early reoperation is clearly associated with
      better long-term patency than intervention after graft failure. Duplex
      ultrasonography is more accurate than ankle:brachial index for graft
      surveillance, but is expensive, time consuming and technically demanding. Non
      invasive estimation of graft impedance is now possible. The present study was
      undertaken to evaluate the utility of non-invasive impedance in detecting the
      failing vein graft. Sixty-nine grafts in 51 patients were followed over a period
      of 12 months (April 1992-March 1993). High risk infrainguinal arterial vein
      bypass patients were entered into a graft surveillance program. Ankle:brachial
      index, non-invasive impedance and duplex ultrasonography were performed upon
      discharge, 1 month after surgery and then at 3-monthly intervals. Non-invasive
      impedance was measured using a mean Doppler flow signal obtained from both upper
      and lower ends of the graft paired with the mean pulse volume recording obtained
      from the distal arterial bed. The mean pulse volume recording and flow signals
      were digitized by discrete Fourier transform and an impedance index generated. An
      impedance index > or = 0.5 was considered abnormal. Impedance results were
      compared with ankle:brachial index, duplex ultrasonography and angiography when
      appropriate, and detected 28 failing and five failed grafts. Non-invasive
      impedance achieved a sensitivity of 91% and a specificity of 94%. Similarly,
      duplex ultrasonography was 91% sensitive and 97% specific, while ankle:brachial
      index was 58% sensitive and 94% specific. Non-invasive impedance is a simple,
      inexpensive and effective test which detects the failing graft and is an
      appropriate first-line alternative to duplex ultrasonography for postoperative
      graft surveillance.

PMID- 8745191
TI  - Significance of radiological diagnosis for detection and staging of inflammatory
      abdominal aortic aneurysm.
AB  - Operative morbidity and mortality are elevated in patients with inflammatory
      abdominal aortic aneurysm. Preoperative identification of inflammatory abdominal
      aortic aneurysm. the detection of the proximal level and of adhesions to adjacent
      structures are important for surgical management. The sensitivity and specificity
      of ultrasonography and computed tomography (CT) for identification and staging in
      13 patients with inflammatory abdominal aortic aneurysm were studied.
      Preoperative radiological diagnoses were validated by intraoperative findings.
      Correct identification of inflammatory abdominal aortic aneurysm could be
      achieved in 85% by the use of CT and in 62% by ultrasonography. The proximal
      level of inflammatory abdominal aortic aneurysm was correctly determined by CT in
      all patients and by ultrasonography in 62%. Using a transperitoneal approach, the
      condition was considered inoperable in two patients as a result of the suprarenal
      extent of the aneurysm and because of unremovable adhesions in two other cases.
      In the latter pair, it was impossible to predict inoperability by radiological
      findings. Sensitivity (85%) and specificity (100%) of standard radiological
      techniques to identify inflammatory changes are high. Inoperability caused by
      suprarenal extent could be detected correctly by routine radiological procedures.
      However, identification of dense adhesions appears uncertain.

PMID- 8745192
TI  - Sequential aortofemoropopliteal/distal bypass for treatment of critical lower
      limb ischaemia.
AB  - Multilevel arterial occlusive disease is often the main cause of critical
      ischaemia of the lower limb. The aim of this study was to determine the
      diagnostic criteria that could help select patients for sequential
      aortofemoropopliteal/distal reconstruction and to compare the results after
      simultaneous and two-stage surgery. Some 1953 aortofemoral reconstructions were
      performed during a 6-year period (1987-1992). In 245 cases (12.5%) sequential
      aortofemorodistal (popliteal or tibia) procedures were performed for critical
      limb ischaemia Fontaine classification grade III and IV. Two-segment
      reconstructions were performed in one stage in 161 cases (group A), and two
      separate operations were performed, the outflow procedure usually following
      within 12 months after inflow surgery, in 84 cases (group B). The preoperative
      mortality rates were 3.2% in group A (five deaths) and 5.9% in group B (five
      deaths). Limb salvage rates were 95.6% at 1 year and 90.4% at 5 years for group A
      and 88.8% at 1 year and 80.0% at 5 years for group B. Primary inflow bypass
      patency rates were 97.7% at 1 year and 91.3% at 5 years for group A and 93.4% at
      1 year and 76.3% at 5 years for group B, while secondary inflow bypass patency
      rates were 98.8% at 1 and 5 years for group A, and 95.3% and 88.3% at 1 and five
      years respectively for group B. Primary outflow bypass patency rates were 91.4%
      at 1 year and 65.5% at 5 years for group A, and 84.9% at 1 year and 59.4% at 5
      years for group B. Secondary outflow bypass patency rates were 92.2% at 1 year
      and 81.8% at 5 years for group A, and 86.1% at 1 year and 65.9% at 5 years for
      group B. The data demonstrate that single-stage multisegment reconstruction for
      multilevel arterial occlusive disease is a safe and effective method of treating
      critical limb ischaemia.

PMID- 8745193
TI  - Hemodynamic improvement in hemorrhagic shock by aortic balloon occlusion and
      hypertonic saline solutions.
AB  - The initial treatment of uncontrolled hemorrhage shock from an abdominal source
      is controversial. The hemodynamic effects of transfemoral diaphragmatic aortic
      occlusion with a balloon followed by a single bolus of hypertonic saline
      solutions have been evaluated in 28 dogs. The animals were submitted to pressure
      driven hemorrhage for 90 min, according to mean arterial pressure in the
      abdominal aorta and randomized into four groups, according to the treatment
      employed at 34 min after hemorrhage. Group 1 dogs (controls) received isotonic
      NaCl (0.9%, 208 mOsm/l, 4 ml/kg) without aortic occlusion; group 2 underwent
      aortic occlusion and received isotonic NaCl (0.9%, 308 mOsm/l, 4 ml/kg): group 3
      were occluded and received hypertonic NaCl (7.5%, 2400 mOsm/l, 4 ml/kg); group 4
      were occluded and received hypertonic sodium acetate (10.5%, 2400 mOsm/l, 4
      ml/kg). There were no significant differences between groups at basal measures
      and also after 30 min of continuous bleeding, when animals presented with severe
      shock, and significant decreases in mean arterial pressure, cardiac index,
      systolic index and cardiac filling pressures; the systemic vascular resistance
      index was increased. Control animals remained in severe shock throughout the
      experiment and three died. The recovery of mean arterial pressure in aortic
      occluded dogs given isotonic NaCl was associated with a marked increase in
      systemic vascular resistance index, without improvements in cardiac index,
      systolic index and cardiac filling pressures. In occluded dogs given hypertonic
      NaCl and NaAc the mean arterial pressure recovery lasted longer, with lower
      increases in systemic vascular resistance index, while the cardiac index,
      systolic index and cardiac filling pressures showed a marked albeit transient
      increase. Injection of hypertonic saline following aortic occlusion produced
      significantly better hemodynamic profiles and should be seriously considered for
      the first treatment in severe uncontrolled hemorrhagic shock from an abdominal
      vascular source.

PMID- 8745194
TI  - Double clostridial mycotic aneurysms of the aorta.
AB  - Mycotic aortic aneurysm continues to present challenging and difficult management
      issues with a significant morbidity and mortality. The offending organism in the
      etiology of this aneurysm can be variable and unusual. The first report of two
      mycotic aortic aneurysms caused by Clostridium septicum in the same patient is
      described here. Presentation and management as well as conditions commonly
      associated with Clostridium septicum infection and a review of all clostridial
      mycotic aortic aneurysms in the English literature are discussed.

PMID- 8745195
TI  - Intravenous leiomyomatosis with intracardiac extension.
AB  - Intravenous leiomyomatosis is a benign smooth muscle tumor of uterine origin
      characterized by grossly visible masses of smooth muscle cells growing within
      venous channels. A case of leiomyomatosis arising in the uterine veins with
      extension into the right iliac veins, vena cava, right atrium, right ventricle
      and into the pulmonary outflow tract is described. The tumor was completely and
      successfully removed by a staged approach with median sternotomy followed by
      laparotomy several days later. A brief review of the literature and a discussion
      of the operative approach are presented.

PMID- 8745196
TI  - Rupture of a dissecting thoracic aortic aneurysm into the pulmonary artery:
      successful surgical repair.
AB  - A rare complication of dissecting thoracic aortic aneurysms is rupture into a
      cardiac chamber or great vessel with fistula formation. A case of congestive
      heart failure caused by a chronic DeBakey type I dissecting aortic aneurysm that
      ruptured into the pulmonary artery is reported. Surgical repair involved closure
      of the fistula followed by graft replacement of the ascending aorta and
      transverse aortic arch. A review of the literature revealed no previous reports
      describing successful repair of this lesion. A clinical picture consistent with
      concomitant aortic dissection and biventricular heart failure, especially when a
      continuous cardiac murmur is present, suggests the diagnosis of an aortopulmonary
      arterial fistula caused by a ruptured dissecting thoracic aortic aneurysm.
      Various imaging studies confirm the diagnosis.

PMID- 8745197
TI  - Prosthetic graft infection in the descending thoracic aorta treated by extra
      anatomic rerouting.
AB  - Prosthetic aortic graft infection is a dreaded complication associated with high
      mortality. Some of the best results have been achieved with removal of the
      infected prosthesis, although this is not always possible in the case of the
      thoracic aorta. A patient with an infected coarctation graft managed by aortic
      rerouting is described here.

PMID- 8745198
TI  - Surgical treatment of an aortopulmonary artery fistula complicating a syphilitic
      aortic aneurysm.
AB  - Spontaneous rupture of an aortic aneurysm into the pulmonary artery is unusual
      and is rarely reported in the literature. The case of a patient with a syphilitic
      aneurysm of the ascending aorta perforated into the pulmonary artery is
      presented. In an attempt to define the best surgical treatment for this
      complication the literature has been comprehensively reviewed.

PMID- 8745199
TI  - Contained rupture of infected abdominal aortic aneurysm due to systemic
      candidiasis.
AB  - A case is reported of contained rupture of an infected abdominal aortic aneurysm
      as a result of vascular catheter-associated candidiasis. Candida was identified
      in the mural thrombus taken from the aneurysm during surgery. Since Candida has
      played an important role in nosocomial infection and catheter-associated sepsis
      during the past decade, it is becoming an increasingly significant pathogen in
      microbial arteritis. Successful treatment included axillobifemoral bypass
      grafting followed by a complete excision of the infected aneurysm,
      retroperitoneal drainage and long-term antifungal therapy. Although infected
      abdominal aortic aneurysm is not common, without surgical intervention it may
      lead to serious consequences, such as rupture or uncontrollable sepsis. As the
      clinical symptoms of this disease are minimal and non-specific during the early
      stages, a high index of suspicion for this condition is essential for precise
      diagnosis and successful treatment. Moreover, initial treatment of candidiasis is
      especially important to prevent this rare but fatal late complication, infected
      abdominal aortic aneurysm.

PMID- 8745200
TI  - Changes in carnitine metabolism with ketone body production in obese glucose
      intolerant patients.
AB  - To elucidate the relationship between carnitine metabolism and plasma ketone body
      concentrations in moderately obese patients with mild glucose intolerance, the
      ketone body and carnitine levels in the basal state were determined in 72 obese
      patients: 20 with normal glucose tolerance (NGT), 29 with impaired glucose
      tolerance (IGT), and 23 with non-insulin-dependent diabetes mellitus (NIDDM)
      having a fasting plasma glucose (FPG) level of less than 200 mg/dl. Total ketone
      body (TKB) levels significantly (P < 0.05) increased in the order of NGT, IGT,
      NIDDM, while the FPG and free fatty acid (FFA) concentrations were significantly
      (P < 0.05) higher in the NIDDM group than in the other two groups. In contrast,
      the insulin, glucagon and glycerol levels were comparable in the three groups.
      The plasma short-chain acylcarnitine (SCAC) concentration and the
      acylcarnitine/free carnitine (AC/FC) ratio were similar in the IGT and NIDDM
      groups, and significantly (P < 0.05) greater than those in the NGT group. The
      AC/FC ratio correlated significantly with the FPG and FFA, but not with the TKB.
      These results suggest that the combination of IGT with simple obesity may trigger
      the acceleration of hepatic ketogenesis in conjunction with an elevated SCAC and
      an increased AC/FC ratio. In addition, the data also imply that, in patients with
      mild NIDDM, factors other than the carnitines may play a greater role in
      enhancing ketonemia.

PMID- 8745201
TI  - Altered [Ca2+]i mobilization in diabetic cardiomyocytes: responses to caffeine,
      KCl, ouabain, and ATP.
AB  - To study the mechanisms mediating intracellular calcium transients involved in
      diabetic cardiac dysfunction, changes in intracellular calcium concentration
      ([Ca2+]i) in response to stimulation by caffeine, ouabain, KCl and ATP were
      studied in single cardiomyocytes (quiescent or electrically-stimulated) isolated
      from streptozotocin (STZ) diabetic rats. [Ca2+]i was measured by fluorescence
      microscopy using fura-2. Peak [Ca2+]i response to caffeine (20 mM) and decline of
      [Ca2+]i (-peak d[Ca2+]i/dt) were decreased in diabetic myocytes. Insulin
      treatment corrected these depressed [Ca2+]i responses. The data suggest a reduced
      sarcoplasmic reticulum (SR) calcium content and a depressed Na-Ca exchange
      activity in diabetic myocytes. Insulin deficiency may play a causal role in these
      changes. The maximum [Ca2+]i increase in response to ouabain was reduced in
      diabetic cells while the sensitivity of diabetic myocytes to ouabain was
      increased. This may be a result of depressed Na-K ATPase and elevated [Na+]i as
      previously reported. The KCl (12.5-50 mM)-induced [Ca2+]i increase was enhanced
      in diabetic cells. Caffeine (20 mM) and dichlorobenzamil (DCB, 10 microM) blocked
      this [Ca2+]i transient to a smaller degree in diabetic cells, but nitrendipine
      effects were similar in diabetic and control cells. These effects may be due to
      the increased L-channel activity and altered features, such as different
      responses to Ca-channel blockers, in diabetes which has previously been reported.
      The maximum response of [Ca2+]i to exogenous ATP was increased in diabetic cells
      while the sensitivity remained unchanged. The mechanisms underlying this enhanced
      response may be similar to the KCl-induced [Ca2+]i changes in diabetes.

PMID- 8745202
TI  - CA-repeated microsatellite polymorphism of the glucokinase gene and its
      association with non-insulin-dependent diabetes mellitus in Taiwanese.
AB  - Mutation of the glucokinase gene has recently been identified as a cause of
      maturity-onset diabetes of the young (MODY), a subset of non-insulin-dependent
      diabetes mellitus (NIDDM). However, its role in the wide variety of NIDDM remains
      controversial due to conflicting reports of association studies, negative results
      of linkage studies and low prevalence of glucokinase mutations in the common
      variety of NIDDM. In this study, two (CA)n-microsatellite polymorphisms flanking
      both ends of the glucokinase gene, termed GCK1 and GCK2, were used to evaluate
      the role of glucokinase on NIDDM susceptibility of Taiwanese. For GCK1, three
      alleles (Z,Z+2 and Z+4 with a polymorphic information content index (PIC) of
      0.53) and six genotypes were evident in 119 Taiwanese. When compared with control
      subjects, the NIDDM group had a much less frequency of the Z+2 allele (14.0% vs.
      23.9%). In addition, the Z+2 allele was noted to have a marginal protective
      effect for NIDDM in Taiwanese with the odds ratio of 0.52 (95% confidence
      interval (C.I.) 0.26-1.03, P = 0.058). For GCK2, four alleles (0, 2, 4 and 6 with
      a PIC of 0.48) and seven genotypes were identified. There was no significant
      difference in allele frequency between NIDDM and control groups in the locus of
      GCK2. Our data were in agreement with reports from American Blacks, Mauritian
      Creoles, Asian Indians, Japanese and Finnish--that there is a positive
      association of GCK1 and a negative association of GCK2 with NIDDM. Furthermore,
      the Z+2 allele was a protective factor for NIDDM in Taiwanese.

PMID- 8745203
TI  - Insulin versus a combination of insulin and sulfonylurea in the treatment of
      NIDDM patients with secondary oral failure.
AB  - AIM: Comparison of the effectiveness of combined therapy vs. an insulin regimen
      in NIDDM patients with secondary failure of oral hypoglycemic agents. RESEARCH
      DESIGN, PATIENTS AND METHODS: 27 NIDDM patients were randomly allocated to Group
      A (n = 14, insulin) and Group B (n = 13, insulin and sulfonylurea) with crossover
      after 3 months. After the next 3 months a decision was made about the further
      treatment according to the metabolic control. The patients were then treated for
      another year with the more successful regimen. Metabolic control, residual beta
      cell secretory capacity, degree of peripheral insulin resistance (clamp) and
      insulin dose were followed during the whole study. RESULTS: (median,
      interquartile range, in brackets; *, statistically significant difference at P <
      0.05): the combined therapy was better than insulin alone in 2/3 of patients.
      Glycemic control was better (HbA1c at 3 months: Group A = 7.9(1.1)% vs. Group B =
      7.0(0.5)%*; HbA1c at 6 months: Group A = 7.4(1.5)% vs. Group B = 8.1(1.5)%.
      Insulin dose was lower during the combined therapy in the first 3 months: Group A
      = 0.62(0.18) U/kg body weight vs. Group B = 0.39(0.16) U/kg body weight*.
      Combined treatment was associated with increased C-peptide excretion both fasting
      and postprandially. No significant differences in peripheral insulin resistance
      were noted between the two groups. The combined treatment remained successful
      even after one year. The two groups of patients with different effective
      treatment did not differ significantly in any of the observed parameters.
      CONCLUSIONS: the combined therapy was more effective than insulin alone. Its
      favourable effect persisted after treatment for a year. It seems better to start
      the treatment of the oral failure with combined therapy compared with insulin
      first and later followed by combined therapy. On the basis of the observed
      parameters it is impossible to determine in advance which kind of treatment is
      more suitable for the individual patient.

PMID- 8745204
TI  - Effect of eicosapentaenoic acid and docosahexaenoic acid on diabetic osteopenia.
AB  - To evaluate the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA), which are polyunsaturated fatty acids, on diabetic osteopenia, we measured
      the bone fragility in streptozotocin-induced diabetic rats. The fragility of
      femur was increased in diabetic rats, which was prevented in part by EPA or DHA.
      Moreover, EPA prevented osteopenia even in diabetic rats fed a low zinc feed,
      which was a potent accelerator of diabetic osteopenia. Plasma alkaline
      phosphatase activity and parathyroid hormone level showed no difference between
      the two groups of diabetic rats with or without EPA. Urinary excretion of calcium
      and phosphate was increased and plasma inorganic phosphate level was high in
      diabetic rats, suggesting severe mineral loss. In diabetic rats fed EPA, although
      urinary and plasma calcium levels did not change significantly, urinary phosphate
      excretion and plasma inorganic phosphate concentration were slightly lowered,
      which suggested that EPA may have an effect in suppressing phosphate release from
      bones in diabetic rats. These data suggest that EPA and DHA could be effective on
      diabetic osteopenia, but to elucidate the precise mechanisms, further
      examinations will be needed.

PMID- 8745205
TI  - Glycaemic control of insulin-dependent diabetes mellitus in Sudan: influence of
      insulin shortage.
AB  - Insulin availability and routine diabetes care were cross-sectionally
      investigated in 122 (M/F; 59/63) insulin-dependent diabetic patients aged 6-60
      years with > or = 1 year duration using a structured questionnaire interview
      followed by a free conversation. Haemoglobin A1c, blood glucose, and serum lipids
      were measured in the fasting state to assess the metabolic control. Only 12% of
      the patients had acceptable glycaemic control (HbA1c < 7.5%). Increased age,
      shorter diabetes duration, and higher body mass index were associated with better
      metabolic control. Omission or reduction of the insulin dose was experienced by
      51% of the patients due to insulin shortage. The interview data consistently
      indicated that insulin non-availability had induced poor compliance to therapy
      regimens and lack of motivation for optimum glycaemic control. Due to limited
      resources, most of the patients received insufficient diabetes care and
      education, leading to lower rates of clinic attendance (55%), and dietary non
      compliance (78.5%). Elevated haemoglobin A1c was associated with higher fasting
      blood glucose levels (P < 0.001), serum triglycerides (P < 0.05), and urinary
      glucose (P < 0.001). Measurable fasting C-peptide was observed in 52.5% of the
      patients and was related to the age at diagnosis, and body mass index (P < 0.001
      for both). There is a considerable potential to improve diabetes care and
      education practice, and if accessibility to insulin is simultaneously
      facilitated, the glycaemic control in Sudanese diabetic patients will improve.

PMID- 8745206
TI  - The relationship between insulin resistance and insulin secretion in Japanese
      subjects with borderline glucose intolerance.
AB  - Insulin resistance and impaired insulin secretion can be involved in the
      development of non-insulin-dependent diabetes mellitus (NIDDM), but their
      relative importance or temporal relationship are poorly understood. To elucidate
      this issue, we studied 51 subjects with borderline glucose intolerance (BGI) and
      18 normal glucose tolerant subjects (NGT) according to the Japan Diabetes Society
      criteria. The glucose infusion rate (GIR, mg/kg/min), an index of whole body
      insulin resistance (IR), was measured by the euglycemic (80 mg/dl)
      hyperinsulinemic clamp technique (insulin infusion rate 1.12 mU/kg/min).
      Insulinogenic index (delta IRI/delta BS at 30 min) and the insulin area under the
      curve during a 75-g oral glucose tolerance test (OGTT) were estimated. In the BGI
      subjects, the GIR values showed marked variation ranging from 2.24 to 10.44
      mg/kg/min (5.54 +/- 0.31, mean +/- S.E.M.). The GIR values were lower in obese
      BGI subjects compared with non-obese BGI and NGT subjects, and the insulin area
      was markedly higher in BGI subjects with increased insulin resistance. There was
      a significant negative correlation between the GIR values and the insulin area or
      delta IRI/delta BS (30') ratio in the subjects with BGI either in the whole group
      or solely in the non-obese group. We conclude that the increased insulin
      secretion compensates for the peripheral insulin resistance of subjects with
      slightly deteriorated glucose tolerance, implying that insulin resistance plays
      an important role in the pathogenesis of NIDDM in some fraction of Japanese
      population.

PMID- 8745207
TI  - Pattern of long-term complications in Sudanese insulin-treated diabetic patients.
AB  - The prevalence of long-term micro- and macrovascular complications was studied in
      128 (M/F; 62:66) Sudanese insulin-treated diabetic patients aged 15-75 years and
      with > or = 1 year duration. Patients were recruited from the out-patient clinics
      of the general hospitals in three States in Sudan. Haemoglobin A1c (HbA1c) was
      measured to assess the degree of metabolic control. The prevalence of
      microvascular complications was, retinopathy 43%, nephropathy 22% and neuropathy
      37%. For macrovascular complications the prevalence was, cardiovascular disease
      28%, peripheral vascular disease 10% and cerebrovascular accidents 5.5%. The
      overall prevalence of long-term complications was 67%. Patients with these
      complications were significantly older (P < 0.005), had longer disease duration
      (P < 0.001), and had higher serum cholesterol and triglyceride concentration (P <
      0.001 and P < 0.05, respectively). The glycaemic control was adequate in only
      12.5% of the patients, and was not related to the prevalence of complications.
      Sudanese diabetic patients are more prone to both microvascular and macrovascular
      complications than previously reported. More attention from the patients and
      clinicians is required and all efforts should be made to reduce the incidence of
      these complications.

PMID- 8745208
TI  - A case of primary and generalized allergy to human insulin with no history of any
      prior insulin exposure.
AB  - A generalized hypersensitivity reaction against human insulin was demonstrated in
      a non-insulin dependent diabetic man treated with only human insulin. The patient
      had no history of previous insulin exposure or atopy. Because of negative
      reactions to intracutaneous tests of constituents of the formulation and the
      presence of insulin-specific IgE antibody, this generalized allergic reaction
      seems to have been caused by the human insulin itself. Although desensitization
      was not effective, this allergic reaction was improved both by the treatment with
      oral antihistamines and desensitization. Cases of generalized and primary allergy
      against human insulin have been rarely reported making this a very rare case.

PMID- 8745209
TI  - Differential regulation of mRNA specific for beta 1- and beta 2-adrenergic
      receptors in human failing hearts. Evaluation of the absolute cardiac mRNA levels
      by two independent methods.
AB  - In human heart failure beta-adrenergic receptors are downregulated which
      contributes to the reduced responsiveness to positive inotropic beta-agonists in
      the diseased heart. The present study addressed the question whether the number
      of beta-adrenergic receptors in the failing human heart is regulated at the level
      of the mRNA and whether the absolute steady-state levels of subtype-specific
      mRNAs mirror the expression of receptor-subtype proteins in human heart. In a
      collaborative effort, two different and independent methods, performed in two
      independent laboratories, reverse transcription followed by polymerase chain
      reaction (RT-PCR) and RNase protection assays, were used to determine the
      absolute steady-state levels of beta 1- and beta 2-adrenergic receptor mRNAs in
      control (NF) and in failing human hearts. As determined by quantitative RT-PCR
      the beta 1-mRNA was significantly reduced from 0.98 +/- 0.12 (n = 10) to 0.49 +/-
      0.11 pg/microgram total RNA in dilated cardiomyopathy (dCMP, n = 7) and to 0.40
      +/- 0.11 pg/microgram total RNA in ischemic cardiomyopathy (iCMP, n = 8). The
      steady-state levels of mRNA specific for beta 2-adrenergic receptors also tended
      to be decreased but without reaching significance (NF: 0.16 +/- 0.05, dCMP: 0.11
      +/- 0.03, iCMP: 0.13 +/- 0.04 pg/microgram total RNA). RNase protection assays
      revealed similar values. beta 1-mRNA was found to be significantly reduced from
      1.22 +/- 0.22 in NF (n = 10) to 0.63 +/- 0.14 pg/microgram total RNA in dCMP (n =
      5) and to 0.52 +/- 0.1 pg/microgram total RNA in iCMP (n = 8). The beta 2-mRNA
      also tended to be lower in dCMP and in iCMP as compared to NF but again without
      reaching significance (NF: 0.14 +/- 0.02, dCMP: 0.099 +/- 0.02, iCMP 0.107 +/-
      0.02 pg/microgram total RNA). This is the first study to demonstrate in parallel
      by two different methods performed independently in two laboratories that the
      ratio of beta 1- and beta 2-adrenergic receptor densities in the left ventricle
      of the normal human heart of about 80/20 is closely related to the absolute
      steady state concentrations of their specific mRNA. In addition, the magnitude of
      the decrease in mRNA-levels of beta 1- and beta 2-adrenergic receptors in the
      failing human heart closely correlates with the decrease of the respective
      receptor proteins. These data suggest that the predominant regulation of beta
      adrenergic receptors occurs at the mRNA level.

PMID- 8745210
TI  - Stimulation of the Na+/Ca2+ exchanger by phenylephrine, angiotensin II and
      endothelin 1.
AB  - The Na+/Ca2+ exchanger plays an important role in the maintenance of calcium
      homeostasis in the heart. Therefore, factors which regulate the exchanger have a
      significant impact on cardiac function. Previously, we showed that the non
      hydrolysable GTP analog, 5'guanylyl imidodiphosphate [Gpp(NH)p], stimulates
      Na+/Ca2+ exchange activity, implying the involvement of a G protein in exchanger
      regulation. In this study, we examined the effect of G protein agonists on
      Na+/Ca2+ exchanger activity. Isoproterenol, a Gs agonist, had no effect on
      exchanger activity. Likewise, the Gi agonist, carbachol, did not influence
      Na+/Ca2+ exchanger activity. Since these G proteins couple to the adenylate
      cyclase system, it would appear that cAMP-linked events do not regulate the
      Na+/Ca2+ exchanger. We next examined the influence of Gq-linked agonists on
      exchanger activity. Phenylephrine, an alpha 1-adrenergic agonist, increased
      Na+/Ca2+ exchanger activity up to 111% with an EC50 of 21 microM. Moreover, the
      Na+/Ca2+ exchanger activity was enhanced by angiotensin II and endothelin 1,
      which caused maximal stimulation of exchanger activity up to 125% and 211%,
      respectively. The selective protein kinase C inhibitor chelerythrine
      significantly attenuated the ability of phenylephrine and angiotensin II to
      stimulate the Na+/Ca2+ exchanger. In addition, the protein kinase C activator,
      phorbol 12-myristate 13-acetate, stimulated exchanger activity by 32%, raising
      the possibility that all three Gq agonists mediate their actions in part through
      the promotion of phospholipase C activity and the subsequent activation of
      protein kinase C. The contribution of Na+/Ca2+ exchange to the actions of
      phenylephrine, angiotensin II, and endothelin 1 is discussed.

PMID- 8745211
TI  - Influence of fibroblast growth factor (bFGF) and insulin-like growth factor (IGF
      I) on cytoskeletal and contractile structures and on atrial natriuretic factor
      (ANF) expression in adult rat ventricular cardiomyocytes in culture.
AB  - The effects of basic fibroblast growth factor (bFGF) and of insulin-like growth
      factor-I (IGF-I) on structural (actin cytoskeleton and myofibrillar apparatus)
      remodeling and on the expression of atrial natriuretic factor (ANF) in adult rat
      ventricular cardiomyocytes have been followed during the hypertrophy reaction up
      to 3 weeks in culture. Cells attach to the substratum spread into polygonal
      shapes with pseudopodia and resume contractile function after 1 week. A well
      structured actin cytoskeleton with stress fiber-like structures fills the cell
      bodies and the extensions. In controls and with IGF-I cells grow to the double
      volume while bFGF induces a four-fold increase. The myofibrillar apparatus
      follows the actin stress fiber-like structures in growing out into the cell
      periphery. Immunoreactive ANF granules develop and are concentrated around the
      nuclear region. The fetally occurring alpha-smooth muscle actin (alpha-sm-actin)
      is re-expressed in stress fiber-like structures. IGF-I down-regulates alpha-sm
      actin and ANF and promotes myofibrillar growth whereas bFGF has the opposite
      effect by up-regulating alpha-sm-actin (on average five to six times more than in
      controls as analysed by immunoblotting) and ANF. In addition, bFGF restricts
      myofibrillar growth with a sharp boundary in the perinuclear region. The most
      dense packing of alpha-sm-actin in the cytoskeleton is found just outside the
      area containing the myofibrils; so alpha-sm-actin seems to restrict myofibrillar
      assembly and growth. These cells are nevertheless beating like the controls. The
      relative increase of cytoskeletal structures with the concomitant lack of growth
      of myofibrils, is mostly due to an increase in alpha-sarcomeric actin (alpha
      cardiac and alpha-skeletal muscle actin) and in alpha-sm-actin.

PMID- 8745212
TI  - Upregulation of collagen type I gene expression in the ventricular myocardium of
      thyroidectomized male and female rats.
AB  - It is established that thyroxine-induced ventricular hypertrophy is associated
      with downregulation of collagen type I gene expression and increased collagen
      turnover in the ventricular tissue. The present study was undertaken to test the
      hypothesis that circulating thyroid hormones may have a regulatory impact on the
      biosynthesis of the collagen matrix in the heart. To this end, we determined
      collagen gene expression and deposition in the hearts of male and female Sprague
      Dawley rats after surgical thyroidectomy. The serum levels of 3,3'5
      triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4) in thyroidectomized
      and age/sex-matched sham-operated rats were determined by radioimmunoassay and
      fluorescence analysis of the serum, respectively. On day 14 post-surgery, the
      plasma levels of both T3 and T4 in thyroidectomized rats were decreased by
      greater than 85% compared with those in matching sham-operated control rats. At
      this time, Northern analysis of ventricular RNA from thyroidectomized rats showed
      a 160% (P = 0.0079) increase for pro alpha 1 (I) and a 43% increase (P = 0.0484)
      for pro alpha 2 (I) collagen mRNAs in the ventricular tissue of male rats
      compared with that in the heart of age-matched, sham-operated control rats. In
      the female rats, thyroidectomy led to 63% (P = 0.0469) increase in the abundance
      of pro alpha 1 (I) collagen and 50% (P = 0.034) increase for pro alpha 2 (I)
      collagen in ventricular tissue. At the protein level, the amount of collagen type
      I as determined by immuno-slot blotting of ventricular homogenates, was increased
      in the ventricular tissue of both male (131%, P = 0.0371) and female (108%, P =
      0.0464) rats. Comparison of the changes in males v females showed relatively
      greater increases in the level of collagen type I mRNA and protein in ventricular
      tissue of thyroidectomized males. Of particular note, were the increases in the
      immunoreactive TGF-beta in ventricular tissue of thyroidectomized male and female
      rats which showed a pattern similar to that of changes in collagen type I.
      Immunofluorescent light microscopy of frozen heart sections, showed significant
      remodeling of the type I collagen fibers in the ventricular myocardium of
      thyroidectomized rats compared with age/sex-matched sham-operated rat heart.
      Together, these findings suggest that circulating thyroid hormones play a role in
      physiological regulation of collagen type I biosynthesis in the heart and this
      role may vary in males and females. They further suggest that normal production
      of collagen matrix in the heart may be dependent on the functional status of
      thyroid hormones.

PMID- 8745213
TI  - Modulation of ryanodine binding to the cardiac Ca2+ release channel by
      arachidonic acid.
AB  - Effects of arachidonic acid (AA) on the Ca2+ release channels in cardiac
      sarcoplasmic reticulum were examined by the 3H-ryanodine binding method. The
      samples used were membrane vesicles of junction sarcoplasmic reticulum (JSR) and
      solubilized ryanodine receptor proteins. AA inhibited the amount of hot ryanodine
      bound to its receptor in both types of samples and this inhibitory effect was
      dose-dependent. The Khalf values of the dose-response curve were 12 and 97 microM
      in the JSR membrane vesicles and the solubilized proteins, respectively.
      Moreover, Michaelis, Scatchard and Lineweaver-Burk analyses were performed to
      evaluate Kd, Bmax and Kd/Bmax values. During exposure to AA, the Kd value
      increased while the Bmax value decreased. These results suggest that AA directly
      modifies the structure of the ryanodine binding site.

PMID- 8745214
TI  - Changes in beta-actin mRNA expression in remodeling canine myocardium.
AB  - Beta-actin, a cytoskeletal protein important in the maintenance of
      cytoarchitecture, has long been thought to be expressed constitutively in
      myocardial tissue. As such, beta-actin mRNA has been used as a control gene in a
      wide range of experiments. However, we have uncovered consistent changes in beta
      actin mRNA expression in canine myocardium remodeling as a result of insult to
      the left ventricle. The experimental canine models used were either DC shock
      damage to the left ventricle or volume overload resulting from severe mitral
      regurgitation. The remodeling process in both canine models is characterized by
      an increase in left ventricular mass. PCR amplification using primers designed to
      selectively amplify the 3' end and a portion of the 3' untranslated region of
      beta-actin mRNA resulted in the generation of a 297 base pair product predominant
      only in normal canine myocardium and a 472 base pair product that became
      increasingly prominent from 1 to 30 days after DC shock damage to the left
      ventricle and from 10 to 90 days after creation of mitral regurgitation. Northern
      analysis showed a three-fold increase in beta-actin mRNA after either DC shock or
      creation of mitral regurgitation. Western analysis revealed an early increase in
      beta-actin protein followed by an apparent decrease to below baseline levels.
      These observations suggest that changes in beta-actin mRNA expression accompany
      the structural alterations that occur in response to myocardial damage. Whether
      or not the changes in beta-actin mRNA expression play a role in mediating these
      structural alterations remains to be determined.

PMID- 8745215
TI  - Intracellular [Ca2+] staircase in the isovolumic pressure--frequency relationship
      of Langendorff-perfused rat heart.
AB  - Fluorescence and 31P magnetic resonance spectroscopy have been used to monitor
      simultaneously, the [Ca2+]i staircase and high energy phosphate metabolism in
      isolated Langendorff-perfused rat heart paced at 2, 4 and 6 Hz. In order to
      investigate further the relationship between high energy phosphate metabolism and
      the calcium staircase we perturbed the intracellular phosphocreatine
      (PCr)/creatine concentration with dietary beta-guanidinopropionic acid (beta
      GPA). We have observed that: (a) At 2 Hz stimulation, the ventricular -Ca2+-i
      dependent fluorescence decay is biexponential and continues to decay throughout
      the interstimulus interval; (b) at 4 Hz and 6 Hz, the [Ca2+]i decay is
      monoexponential; (c) end-diastolic [Ca2+]i is elevated at higher stimulation
      frequencies; (d) net [Ca2+]i flux per cycle is reduced at higher stimulation
      frequencies and is therefore correlated inversely with stimulation frequency and
      end-diastolic [Ca2+]i; (e) "heart rate * [Ca2+]i flux product" which is a measure
      of the work done in cycling calcium, is directly proportional to stimulation
      frequency; (f) the hysteresis between peak ventricular isovolumic pressure and
      peak fluorescence is decreased at higher stimulation frequencies; (g) no
      correlation was detected between the PCr/ATP ratio and stimulation frequency; (h)
      despite a 60% decrease in the myocardial PCr/ATP ratio after beta-GPA feeding,
      rat heart is able to maintain the end-diastolic [Ca2+]i-dependent fluorescence,
      and therefore the [Ca2+]i staircase relationship, similar to that of normal rat
      heart. In conclusion, using a physiological stimulation range and substrate
      supply we have observed a negative staircase of both [Ca2+]i and isovolumic
      pressure in whole heart which is not hypoxic. We propose that the inability of
      the sarcoplasmic reticulum to sequester sufficient cytosolic calcium at high
      stimulation frequencies leads to an elevation in end-diastolic [Ca2+]i, decreased
      net calcium flux per cycle resulting in a negative [Ca2+]i staircase and thus a
      negative isovolumic pressure-frequency relationship. We did not detect any
      correlation between steady-state high energy phosphate metabolism and stimulation
      frequency.

PMID- 8745216
TI  - Possible functional linkage between the cardiac dihydropyridine and ryanodine
      receptor: acceleration of rest decay by Bay K 8644.
AB  - The effect of the dihydropyridine L-Type Ca chanel agonist Bay K 8644 on post
      rest contractions in ferret ventricular muscle and isolated myocytes was
      investigated. Bay K 8644 was shown to abolish rest potentiation and greatly
      accelerate rest decay. The post-rest contraction suppressed by Bay K 8644 was
      accompanied by action potentials of large amplitude and longer duration, but
      voltage-clamp measurements showed that this suppression was not due to a supra
      optimal ICa trigger. Caffeine-induced contractures and rapid cooling contractures
      demonstrated an accelerated rest-dependent decline in sarcoplasmic reticulum (SR)
      Ca content in the presence of Bay K 8644, which was present even with Ca-free
      superfusion during rest. Thus, the Bay K 8644-induced decline of SR Ca during
      rest was independent of extracellular Ca or ICa. To explore whether the binding
      of Bay K 8644 to the dihydropyridine receptor could alter the SR Ca release
      channel/ryanodine receptor in a more direct way, ryanodine binding was measured
      in the absence and presence of Bay K 8644. Ryanodine binding to isolated ferret
      ventricular myocytes was increased by Bay K 8644 under conditions where
      sarcolemmal-SR junctions might be expected to be intact, but not after physical
      disruption. These results are consistent with a working hypothesis where Bay K
      8644 may bind to the dihydropyridine receptor and this may lead to physical
      changes in the linkage between the dihydropridine receptor and a subset of
      ryanodine receptors, thereby increasing the opening of the SR Ca release channel
      during rest (and accelerating resting Ca loss).

PMID- 8745217
TI  - Elevated DNase I levels in human idiopathic dilated cardiomyopathy: an indicator
      of apoptosis?
AB  - This is the first report to determine deoxyribonuclease I (DNase I) levels in the
      human myocardium and the first to demonstrate an increased DNase I level
      associated with end-stage heart failure due to idiopathic dilated cardiomyopathy
      (IDCM) compared to non-diseased heart samples. Left ventricular samples were
      obtained following transplantation from failing hearts of 13 patients diagnosed
      with IDCM and from four unused donor hearts. Using a zymogram technique, we show
      that the DNase I levels of the IDCM heart samples were significantly elevated
      (range 0.65-2.75 pg DNase I/microgram protein, mean +/- S.E. of 1.69 +/- 0.22
      pg/micrograms) compared to four non-diseased, donor heart samples (range 0.12
      0.35 pg/microgram protein, mean +/- S.E. of 0.22 +/- 0.05 pg/microgram). The
      DNase I extracted from heart tissue was characterized by: (1) a co-migration with
      bovine pancreatic DNase I; (2) a pH dependence consistent with DNase I; (3) a
      dependence of its activity on both Ca2+ and Mg2+ and an inhibition by Zn2+; and
      (4) an inhibition of its activity in the presence of monomeric rabbit skeletal
      muscle actin. The elevated DNase I levels associated with heart failure due to
      IDCM suggests that apoptosis may be implicated in pathophysiology of this
      disorder.

PMID- 8745218
TI  - Effect of reversible ischemia on the activity of the mitochondrial ATPase:
      relationship to ischemic preconditioning.
AB  - The mitochondrial ATPase enzyme accounts for roughly 35-50% of the overall energy
      demand that leads to ATP depletion under conditions of severe myocardial
      ischemia. In larger mammalian hearts, this energy squandering action of the
      ATPase is modulated by an endogenous inhibitor protein. The present studies were
      undertaken to characterize the time course of inhibition of the mitochondrial
      ATPase in canine myocardium under conditions of severe regional ischemia in vivo.
      In addition, we determined if the energy sparing effects of ischemic
      preconditioning (PC) can be explained by persistent inhibition of the
      mitochondrial ATPase enzyme. The circumflex coronary artery was ligated for 1.5
      min (n = 4), 5 min (n = 6), or 15 min (n = 5). In a separate group (n = 7),
      hearts were preconditioned by four 5-min periods of ischemia each followed by 5
      min of reperfusion. Sub-mitochondrial particles were prepared from the sub
      endocardial zone of the ischemic and non-ischemic regions and were assayed for
      oligomycin-sensitive ATPase activity. ATPase activity was reduced to about 79% at
      1.5 min and to approximately 55% at 5 and 15 min of ischemia, relative to non
      ischemic tissue from the same heart. The rate of HEP utilization slowed
      concurrently with the development of ATPase inhibition. In preconditioned
      myocardium, ATPase activity was not significantly different from control
      myocardium from the same heart. We conclude that the early inhibition of the
      mitochondrial ATPase activity slows the utilization of high energy phosphate and
      thereby serves as an important endogenous cardioprotective mechanism.
      Nevertheless, altered activity of the ATPase is not the explanation of the energy
      sparing effect of ischemic preconditioning.

PMID- 8745219
TI  - Characterization of cardiac gene cis-regulatory elements in the early stages of
      chicken heart morphogenesis.
AB  - To study transcriptional regulation during early stages of cardiogenesis, stage
      10-17 chicken embryo hearts were transfected efficiently within the intact embryo
      by application of plasmid DNA complexed to liposomes. Viral regulatory sequences
      and the skeletal alpha-actin, SERCA2 and ANF promoters activated expression of
      reporter genes in the primitive heart tube. Deletion and mutation analysis of the
      skeletal alpha-actin promoter revealed the importance of CArG cis-regulatory
      elements in enhancing transcription of the gene during early heart development.
      These results demonstrate the utility of this method for the identification of
      gene regulatory elements that specify the cardiac phenotype during early stages
      of heart morphogenesis.

PMID- 8745220
TI  - Electrophysiologic and extracellular ionic changes during acute ischemia in
      failing and normal rabbit myocardium.
AB  - The incidence of ventricular arrhythmias is higher in failing hearts than in
      control hearts, especially during acute ischemia. Electrophysiological and
      extracellular ionic changes during acute ischemia in normal and failing rabbit
      myocardium were assessed. Heart failure was induced in rabbits by combined volume
      and pressure overload. In perfused papillary muscles, the onset of electrical
      uncoupling and changes in action potential duration and conduction velocity
      during acute ischemia were determined. In Langendorff-perfused rabbit hearts the
      changes in extracellular potassium concentration ([K+]o) and pH during acute
      global ischemia were studied. In perfused papillary muscles, during the first 10
      min of ischemia, action potential duration at 80% of repolarization decreased
      more in preparations from failing than from control hearts (from 174 to 104 ms
      and from 156 to 119 ms respectively (P < 0.001)). Conduction velocity was
      significantly lower in failing hearts during ischemia (P < 0.005). The onset of
      electrical uncoupling was similar in failing and control hearts (mean +/- S.E.M.,
      17 +/- 1 and 15 +/- 1 min respectively, n.s.). Langendorff-perfused hearts [K+]o,
      after 10 min of ischemia, was 11.0 +/- 0.4 mM in failing and 9.5 +/- 0.3 mM in
      control hearts (P < 0.01), while the change in pH was the same. After
      pretreatment with glibenclamide, an ATP sensitive K+ channel blocker, [K+]o
      reached lower values after 10 min of ischemia in both failing (8.8 +/- 0.5 mM)
      and control hearts (7.2 +/- 0.4 mM). During ischemia, action potential duration
      shortening is more pronounced and conduction velocity is lower in failing
      myocardium than in control myocardium. [K+]o reaches higher values during acute
      ischemia in failing compared with normal myocardium. These changes are not caused
      by an earlier activation of IK.ATP. Increased spatial dispersion in
      electrophysiological parameters and [K+]o over the ischemic border in failing
      hearts may explain the higher propensity for reentrant arrhythmias during acute
      regional ischemia in failing hearts.

PMID- 8745221
TI  - Ischemic/reperfused myocardium can express recombinant protein following direct
      DNA or retroviral injection.
AB  - A non-contracting scar following myocardial infarction can adversely affect
      ventricular topography and hemodynamic function. Gene transfer has the potential
      to prevent or alter such pathophysiological processes. Normal myocardium is a
      proven target for delivery of DNA or viral vectors but the potential for gene
      therapy in ischemic myocardium has not been evaluated. In an initial series of
      experiments, we determined whether the direct injection of reporter genes into
      hearts subjected to coronary artery occlusion followed by reperfusion could
      result in gene expression comparable to the levels observed in non-occluded
      normal hearts. Anesthetized rats were subjected to 15 min or 60 min of proximal
      coronary occlusion or sham operation. Luciferase gene under the control of the
      Rous sarcoma virus promoter was injected directly into the anterior left wall. At
      1 week, high expression of luciferase was observed in both the
      ischemic/reperfused and non-ischemic tissue. Thus DNA transfer by direct
      injection is possible after ischemic injury and uptake and expression are not
      impaired. In a second series of experiments, myocardial infarcts in dogs were
      injected with a beta-galactosidase expressing retroviral vector. LNPOZ. Six to 11
      days later frozen sections revealed macroscopically visible expression of beta
      galactosidase activity. Not only can foreign genes be taken up by direct
      injection of DNA or retroviruses into ischemic/reperfused myocardium but they can
      be transcribed and the protein synthetic machinery of the injured cells can
      produce recombinant polypeptides that retain enzymatic activity. These results
      open the way for the investigation of gene therapy in models of ischemia.

PMID- 8745222
TI  - Coronary vascular morphology in pressure-overload left ventricular hypertrophy.
AB  - To attempt to explain the loss of subendocardial coronary reserve in chronic
      pressure-overload cardiac hypertrophy on a morphologic basis, we measured
      capillary capacity and coronary artery and arteriole medial wall area in dogs
      with moderately severe chronic (1 year) left ventricular hypertrophy (LVH).
      Aortic bands were placed on the ascending aorta of 8-10-week-old puppies of
      either sex, and hearts were perfusion fixed with 2% glutaraldehyde 8-16 months
      later after hemodynamic study while fully conscious. Left ventricular (LV)
      mass/body weight ratio in 11 banded dogs with LV end-diastolic pressure < 12 mmHg
      was 72% greater than in 15 controls (C). There was a decrease in subendocardial
      coronary reserve during adenosine-induced vasodilation with a shift away from the
      subendocardium (endo/epi flow ratio: C = 0.68 +/- 0.05; LVH = 0.34 +/- 0.06; P <
      0.05). In spite of the extensive hypertrophy, image analysis revealed capillary
      density to be equally reduced by only 10-15% in endo, mid and epicardial LV
      regions compared to control dogs, while increased capillary cross-sectional area
      resulted in no change in capillary surface area/myocyte volume or volume
      percentage capillary space. In addition to these data suggesting capillary
      angiogenesis, there was no reduction in arteriolar density, indicating transmural
      increase in arteriolar number, and, as a consequence, increased total length of
      the resistance vessels. Medial area of arterioles and arteries showed a graduated
      increase according to size. We concluded that due to the lack of transmural
      difference in vascular morphology in chronic (1 year) moderately severe LVH,
      these anatomic bases do not play a major role as a cause for the loss of coronary
      reserve. Regional functional differences as a consequence of the morphologic
      alterations, however, cannot be excluded.

PMID- 8745223
TI  - Prevalence and turnover of peptidylglycine alpha-amidating monooxygenase mRNA in
      atrial cardiomyocytes.
AB  - Peptidylglycine alpha-amidating monooxygenase (PAM), the enzyme responsible for
      the alpha-amidation of neuroendocrine peptides, is more prevalent in the atrium
      of the heart than in pituitary or brain. RNase protection assays indicate that
      PAM transcripts account for approximately 0.5% of the mRNA in the neonatal atrium
      and 0.06% of the mRNA in the neonatal ventricle. In primary atrial cardiomyocyte
      cultures PAM mRNA turns over slowly, with a half-life of approximately 20 h.
      Levels of PAM mRNA in primary atrial cardiomyocytes are increased to 16.5% of
      control upon treatment with dexamethasone and decreased to 63% of control upon
      treatment with thyroid hormone.

PMID- 8745224
TI  - Expression of inducible nitric oxide synthase in failing and non-failing human
      heart.
AB  - Recently, a significant activity of inducible nitric oxide synthase (iNOS) has
      been reported in biopsies from failing hearts due to idiopathic dilated
      cardiomyopathy (IDC). Thus, a potential pathophysiological role of iNOS in IDC
      has been stated. In order to investigate, whether iNOS expression is of
      pathophysiological relevance in human heart failure, we measured iNOS protein
      expression and cGMP content in left ventricular myocardium from non-failing and
      failing human hearts. Immunoblot analysis revealed iNOS protein expression in
      four out of six failing hearts from septic patients, whereas no iNOS-protein
      expression was detected in either non-failing human hearts (n = 6) or failing
      hearts due to IDC (n = 9), ischemic heart disease (IHD, n = 7), Becker muscular
      dystrophy (BMD, n = 2) and mitoxantrone-induced toxic cardiomyopathy TCM, n = 1).
      cGMP content was increased by 130% in septic hearts, whereas there was no cGMP
      increase in hearts with IDC. IHD and BMD compared to non-failing hearts. We
      conclude, that the induction of iNOS may play a role in contractile dysfunction
      observed in septic shock, but is unlikely to be of major pathophysiological
      importance in end-stage heart failure due to IDC, IHD, BMD and TCM.

PMID- 8745225
TI  - On the roles of long-chain acyl carnitine accumulation and impaired glucose
      utilization in ischaemic contracture development and tissue damage in the guinea
      pig heart.
AB  - It has been proposed that the presence of increasing concentrations of fatty
      acids may accelerate the development of ischaemic contracture and cardiac damage,
      and that this may be due to long-chain acyl carnitine accumulation and/or
      impairment of glucose utilization. In isolated guinea-pig papillary muscles,
      palmitoyl (DL) carnitine was found to have a positive inotropic effect, with a
      slow onset of action suggestive of an intracellular site of action, and with a
      maximal effect of about two-fold at a concentration of 5-10 microM; higher
      concentrations led to decreased contraction, probably due to increasing detergent
      like effects. In isolated fura-2-loaded chick cardiomyocytes, palmitoyl carnitine
      increased intracellular [Ca2+]; it is proposed that this is the means by which it
      increases contraction. The main hypothesis above was studied using isolated
      guinea-pig hearts perfused with either 11.7 mM or 5 mM glucose, and either
      albumin alone (3%) or albumin bound palmitate (1.5 mM) during low-flow ischaemia
      (92% reduction in flow) for up to 60 min. With 11.7 mM glucose, the presence of
      palmitate caused contracture development and increased enzyme release during
      ischaemia. Contracture also developed when the glucose concentration was reduced
      to 5 mM in the absence of fatty acid, however, in its presence contracture
      developed to a greater extent and with increased enzyme release. Long-chain acyl
      carnitine accumulation was similar in both groups. These studies show that long
      chain acyl carnitine accumulation has the potential to induce contracture during
      ischaemia, although a reduction in glucose availability may also contribute.

PMID- 8745226
TI  - Impaired skeletal muscle fatigue resistance in rats with pressure overload
      induced left ventricular hypertrophy.
AB  - In rats with left ventricular (LV) hypertrophy, we investigated whether
      abnormalities of skeletal muscle could result in reduced exercise tolerance in
      the absence of reduced cardiac function. LV pressure overload was induced by
      partial constriction of the abdominal aorta (AC) with controls subjected to sham
      operation. Cardiac and skeletal muscle function and blood flow were assessed in
      vivo 3 and 6 weeks later. AC induced LV hypertrophy of 41% and 37% at 3 and 6
      weeks post-operation. In AC rats, cardiac index was 31 +/- 8 and 35 +/- 4
      ml/min/100 g at 3 and 6 weeks compared to 38 +/- 4 and 34 +/- 2 ml/min/100 g in
      controls (N.S.). Fatigue index of the soleus (type-I rich) muscle in AC rats was
      reduced by 14% (P < 0.05) at both time points, while that of the tibialis
      anterior (mixed fiber) muscle was unchanged at 3 weeks but reduced by 18% (P <
      0.05) at 6 weeks. Function of the extensor digitorum longus (type-IIB rich)
      muscle was unaltered at both time points. Blood flow at rest was paradoxically
      increased in muscles which exhibited increased fatigue susceptibility. At 3
      weeks, blood flow during fatigue stimulation was reduced by 33% in the soleus
      muscle; the only muscle to exhibit impaired fatigue resistance at this time
      point. Blood flow during stimulation remained unaltered in the EDL and TA
      muscles. Thus, impaired fatigue resistance was observed in skeletal muscle with
      high oxidative and oxidative glycolytic fiber content during the compensatory
      phase of LV hypertrophy, prior to overt cardiac dysfunction. A selective
      impairment of blood flow to these muscles during exercise may play a causal role
      in exercise intolerance.

PMID- 8745227
TI  - Preservation of global cardiac function in the rabbit following protracted
      ischemia/reperfusion using monophosphoryl lipid A (MLA).
AB  - Monophosphoryl lipid A (MLA), a derivative of the minimal substructure of
      lipopolysaccharide (lipid A) possesses immunomodulatory activity of the parent
      lipid A yet enjoys reduced toxicity. It has previously been reported that
      pretreatment with MLA reduces myocardial infarct size and stunning in dogs
      following ischemia and reperfusion. The aim of this study was to evaluate the
      ability of monophosphoryl lipid A (MLA) to preserve global cardiac function and
      peripheral hemodynamics in a rabbit model of prolonged regional ischemia (90
      min), and reperfusion (6 h). An evaluation of potential mechanisms by which MLA
      may preserve cardiac function was also undertaken. Single dose pretreatment with
      MLA (35 micrograms/kg i.v.) 24 h prior to ischemia resulted in significant
      improvement in left ventricular developed pressure, dP/dt, rate-pressure product
      and mean arterial pressure during reperfusion (P < 0.05 v control). Although in
      this model of prolonged ischemia MLA pretreatment did not reduce infarct size
      (54.5 +/- 11.4% in control v 63.3 +/- 8.3% in MLA, P = N.S.), evaluation of
      myocardial adenylate and adenosine catabolite pools at the end of ischemia
      indicated a preservation of ATP and ADP and a decreased production of downstream
      adenosine catabolites including inosine, xanthine and uric acid. Adenosine
      kinase, but not 5'-nucleotidase (5'-NTase) or adenosine deaminase activity
      determined following reperfusion was 76% and 60% higher (P < 0.05) in non-risk
      and post-ischemic myocardium of MLA pretreated rabbits compared with controls.
      Although there was a trend toward lower tissue myeloperoxidase activity in post
      ischemic myocardium from treated rabbits, the results were not significantly
      different from control animals. These results suggest that a 24-h pretreatment
      with MLA, without further treatment during ischemia or reperfusion was associated
      with: (1) preservation of global myocardial function during reperfusion; (2)
      preservation of myocardial high energy adenylates and reduced formation of
      adenosine catabolites during ischemia; (3) elevated myocardial adenosine kinase
      activity. Increased recycling of adenosine to phosphorylated nucleotides may
      result from MLA's affect on adenosine kinase, which could explain the drugs
      effect on adenylate and adenosine metabolite pools.

PMID- 8745228
TI  - Apoptosis and DNA fragmentation in the bulbus cordis of the developing rat heart.
AB  - Histologic, ultrastructural and nick end labeling studies were made of the
      process of apoptosis in the bulbus cordis of rat embryos. Apoptosis was observed
      between the 14th and 16th days of gestational age, at which time the bulbus
      cordis undergoes extensive remodeling. Three types of mesenchymal cells were
      identified in this region: cells undergoing apoptosis, cells engaging in the
      phagocytic removal of apoptotic cells, and cells not involved in either of these
      two processes. Fragmentation of DNA, demonstrated by nick end labeling, was found
      only in the apoptotic cells. The combined use of morphologic and labeling
      techniques is extremely useful in the evaluation of the contribution of apoptosis
      to cardiac morphogenesis.

PMID- 8745229
TI  - The Alfred Meyer Memorial Award.

PMID- 8745230
TI  - Symposium: cell stress genes and the nervous system.

PMID- 8745231
TI  - The stress response.

PMID- 8745232
TI  - Cell stress genes and neuronal protection.

PMID- 8745233
TI  - Cell stress genes and acute CNS injury.

PMID- 8745234
TI  - Regulatory mechanism of stress response in mammalian nervous system during
      cerebral ischaemia or after heat shock.

PMID- 8745235
TI  - Heat shock proteins and the immunopathogenesis of multiple sclerosis.

PMID- 8745236
TI  - Cell stress genes and chronic neurodegenerative disorders.

PMID- 8745237
TI  - Expression of stress genes during development.

PMID- 8745238
TI  - Frontal lobe degeneration: novel ubiquitin-immunoreactive neurites within
      frontotemporal cortex.
AB  - Ubiquitin-protein conjugates have been identified in filamentous inclusions in
      various neurodegenerative disorders. In frontal lobe degeneration (FLD) no
      distinctive histological features have been reported with the exception of some
      ubiquitin-positive intraneuronal inclusions in cases associated with motor neuron
      disease. In the present study, we investigated five FLD cases without motor
      neuron disease using immunohistochemistry. A constant feature in all cases
      consisted of ubiquitin-positive neurites in layers I-III of the frontotemporal
      neocortex. These neurites were not argyrophilic, and could not be labelled with
      various antibodies against tau and neurofilament proteins. Ubiquitin-protein
      conjugates were found in distended dendritic branches, in dendritic spines and in
      smooth slender neurites, probably axons. No ubiquitinated neurites were seen in
      corresponding areas of the brain in aged controls. The nature of ubiquitinated
      proteins in FLD and the reason why they are confined to nerve cell processes is
      unknown but may be understood as part of an ongoing process leading to cell death
      observed in FLD.

PMID- 8745239
TI  - Apoptosis in amyotrophic lateral sclerosis is not restricted to motor neurons.
      Bcl-2 expression is increased in unaffected post-central gyrus.
AB  - We searched for the presence of apoptotic cell death and studied the distribution
      of bcl-2, an oncoprotein that counteracts apoptosis, in amyotrophic lateral
      sclerosis (ALS). Brain and spinal cord specimens from 12 ALS patients were
      compared with those from six non-neurological controls. ALS brain tissue was pre
      selected by the presence of reactive cortical damage. Apoptosis was demonstrated
      by in situ end-labelling of fragmented DNA, a method that is suitable for
      formalin-fixed, paraffin-embedded tissue. All ALS patients exhibited some
      apoptosis, eight of them did so in each of the three central nervous system (CNS)
      levels studied. Apoptosis was not restricted to the motor system, but also
      affected other neuronal and non-neuronal CNS elements. Apoptosis corresponded
      with cell shrinkage, and neuronophagia in Nissl stains and with small Nissl
      positive bodies. None of the non-neurological controls showed as much apoptosis
      as any of the ALS cases. Immunocytochemically, the overall distribution of Bcl-2
      did not differ between ALS and non-neurological controls. In ALS, however, we
      found variable degrees of increased Bcl-2 expressed in the nuclei and in the
      cytoplasm. We found no inverse relationship between apoptosis and bcl-2
      expression.

PMID- 8745240
TI  - Reactive microglia in Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob disease (CJD) is characterized by a loss of neurons accompanied
      by astrogliosis and spongiform changes in the neuropil. It has been recognized
      that reactive microglia occur in CJD but little is known about the regional
      distribution and extent of the microglial activation. We have, therefore,
      examined six brains from cases of sporadic CJD by immunohistochemical labelling
      of grey and white matter microglia from frontal, parietal, temporal, and
      occipital lobes, striatum, thalamus, cerebellum and brain stem with RCA-1, LCA,
      CD68, HLA-DR, and HAM56. Microglial activation occurred in the grey matter where
      astrogliosis and prion protein (PrP) deposits were prominent. Processes of
      activated microglia surrounded the outer rim of spongy vacuoles. A diffuse
      microglial response was seen in the white matter that was immunophenotypically
      different from grey matter. Double-labelling with microglial markers and anti-PrP
      showed that activated microglia did not contain PrP-immunoreactivity. Therefore a
      primary role of microglia in PrP processing seems unlikely. Activated microglia
      may contribute to neuronal damage in CJD due to their cytotoxic potential.

PMID- 8745242
TI  - Hippocampal neuronal atrophy occurs in rhesus macaques following infection with
      simian immunodeficiency virus.
AB  - There is strong evidence that patients with AIDS have loss of cortical neurons.
      In this study we have examined the hippocampus of rhesus monkeys infected with
      simian immunodeficiency virus (SIV) to determine whether neuronal damage occurs
      in this model of human AIDS and to investigate its time course. Twenty-eight
      infected monkeys (23 young [< 9 years] and five elderly [> 16 years]) were
      compared with 11 controls (six young and five elderly). Numbers of nucleolated
      neurons per unit area of section and mean pyramidal cell diameters were measured
      in each CA sub-field of each animal. There was neuronal atrophy in all regions
      examined, as early as 3 months following inoculation. An initial apparent
      increase in neuronal density at 3 months did not reach statistical significance.
      In younger animals, however, there was a later, significant association between
      the reduction in neuronal density and duration of infection. Elderly animals were
      only examined at a single, early time point. These results show that there is
      neuronal pathology following infection with SIV and that there is probably
      subsequent neuronal death.

PMID- 8745241
TI  - Activation of nuclear factor kappa B in brains from children with HIV-1
      encephalitis.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous
      system is associated with decreased neuronal density in discrete areas of the
      brain. Neuronal loss may occur via apoptosis, initiated by soluble neurotoxic
      factors secreted from HIV-1 infected macrophages and microglia. To examine
      further the molecular events involved in HIV-1 neuropathogenesis, we assessed the
      activity of NF kappa B, an inducible transcription factor involved in the
      activation of multiple proinflammatory, and potentially neurotoxic, genes. NF
      kappa B was analysed by immunocytochemistry using specific antisera to the NF
      kappa B p. 50 and p. 65 subunits. Brains from children with HIV-1 encephalitis
      and progressive encephalopathy were found to contain increased numbers of NF
      kappa B immunoreactive cells, relative to control brains (HIV-1 negative, or HIV
      1 positive without encephalitis). Double-labelling studies using antibodies to
      CD68, or RCA-1 lectin, markers for cells of monocyte/macrophage lineage, revealed
      an increase in the number of microglia and macrophages with nuclear
      immunoreactivity for NF kappa B in association with HIV-1 encephalitis. NF kappa
      B positive multinucleated giant cells were also detected, as were cells which
      contained both NF kappa B and HIV-1 antigen. In contrast, the number of neurons
      and GFAP-positive astrocytes that were immunoreactive for NF kappa B was
      approximately the same in all groups of subjects. These data are consistent with
      the hypothesis that persistent, high-level activation of NF kappa B may promote
      the sustained production of neurotoxins by microglia and macrophages during HIV-1
      encephalitis.

PMID- 8745243
TI  - Low susceptibility of resident microglia to simian immunodeficiency virus
      replication during the early stages of infection.
AB  - To assess the susceptibility of resident microglia to simian immunodeficiency
      virus (SIV) infection, we analysed the brains of rhesus macaques after
      intracerebral (i.c.) inoculation of the virus into the central region at 7 days,
      1, 2 and 3 months post-inoculation (p.i.). The brains of animals showed the same
      moderate neuropathological changes in central, frontal and parietal regions of
      the brain, characterized by gliosis, microglial nodules, perivascular infiltrates
      and occasional white matter pallor and similar low numbers of infected cells
      detected by in situ hybridization. These results, showing that i.c. inoculation
      did not lead to preferential infection of brain tissue, even near the inoculation
      point at 7 days p.i., provide evidence for the low susceptibility of resident
      microglia to SIV replication during the early stages of infection.

PMID- 8745244
TI  - Cytochrome c oxidase deficiency in zidovudine myopathy affects perifascicular
      muscle fibres and arterial smooth muscle cells.
AB  - In order to assess the pathogenesis of myopathological alterations induced by
      zidovudine, we studied muscle samples from 21 patients infected by human
      immunodeficiency virus with zidovudine myopathy. Cytochrome c oxidase
      histoenzymatic reaction was evaluated in skeletal muscle fibres and arterial
      smooth muscle cells. Other investigations included immunocytochemistry for
      membrane attack complex and endomysial capillary counts. All patients had partial
      cytochrome c oxidase deficiency. A perifascicular distribution of cytochrome c
      oxidase-deficient fibres was found in 14 of 21 patients. Cytochrome c oxidase
      deficient fibres were significantly more frequent in perifascicular areas than in
      the complete muscle sections (28% vs 12%, P < 0.001). Cytochrome c oxidase
      deficient arteries were found in 11 patients, of whom 10 also had a
      perifascicular deficiency. Mononuclear microvascular inflammation was observed in
      four patients and membrane attack complex deposition in capillary walls in two
      patients. The capillary counts were not significantly different in the patients
      and in the controls. These results suggest that, in addition to a direct action
      of zidovudine on mitochondrial DNA, chronic muscle ischaemia related to
      zidovudine-induced vascular dysfunction might be implicated at the inception of
      muscle damage in zidovudine myopathy.

PMID- 8745245
TI  - Rapid progress in the field of infectious and autoimmune disorders of the nervous
      system.

PMID- 8745246
TI  - Immunisation of sheep with an integral membrane glycoprotein complex of
      Haemonchus contortus and with its major polypeptide components.
AB  - Sheep were immunised against Haemonchus contortus with an integral membrane
      glycoprotein complex isolated from the intestines of the parasite as antigen.
      This antigen has been termed Haemonchus galactose-containing glycoprotein
      complex. Sodium dodecyl sulphate (SDS) polyacrylamide gel analysis has shown that
      it is composed of several polypeptides but so far these have proved refractory to
      separation when in the native state. However when dissociated by SDS, it was
      found to be as efficacious as in its native state, although it was less
      consistently protective when tested after being dissociated and reduced. An
      attempt was therefore made to identify the protective ingredient(s) of the
      dissociated complex by testing its major polypeptides individually after they had
      been separated on SDS polyacrylamide gels under non-reducing conditions. Partial
      protection was induced by protein bands with molecular weights of about 200 kD
      and less than 50 kD, but none of the individual fractions tested was as
      efficacious as the unseparated complex, suggesting that either more than one
      component was essential for a consistent effect or that the separation technique
      had damaged crucial protective epitopes.

PMID- 8745247
TI  - Detection of gastrointestinal nematodes by a coproantigen capture ELISA.
AB  - An assay is described for the quantitative detection of excretory/secretory
      antigens liberated by the intestinal nematode Heligmosomoides polygyrus and
      voided in the host's faeces. A rabbit polyclonal antiserum to the antigens
      detected them in a dose-dependent manner and was sufficiently sensitive to
      recognise infection in mice carrying a mean worm burden of nine worms. The assay
      was specific, giving higher optical density readings with the faeces of mice
      infected with H polygyrus than with faeces from mice carrying patent infections
      with Trichuris muris, Hymenolepsis microstoma or the intestinal phase of
      Trichinella spiralis, or with faeces from rats carrying Hymenolepis diminuta or
      hamsters carrying Necator americanus or Ancylostoma ceylanicum. It detected the
      parasite antigens in faeces stored for eight weeks at -20, 4 or 20 degrees C and
      could detect prepatent infections. The assay has potential for the development of
      infection intensity-sensitive assays for gastrointestinal nematodes and for the
      detection of animals harbouring the arrested larvae of parasites.

PMID- 8745248
TI  - Effect of subclinical lead toxicity on the immune response of chickens to
      Newcastle disease virus vaccine.
AB  - The effect of lead acetate (20 and 40 mg kg-1 bodyweight daily) administered via
      the crop from day old to 56 days of age on the immune response to Newcastle
      disease virus vaccine (NDVV, La Sota strain) was studied in 354 Lohman chickens.
      Lead decreased the mitogenic response of peripheral blood lymphocytes (PBL) to
      phytohaemagglutinin-P (PHA-P) in birds vaccinated with NDVV. It also decreased
      the weights of the bursa of Fabricius, the thymus glands and the spleen relative
      to bodyweight. Lead administration decreased the antibody titre to NDVV in the
      vaccinated groups. The percentage mortality due to a challenge with a virulent
      velogenic Newcastle disease virus was higher in the lead intoxicated birds.

PMID- 8745249
TI  - Retinal pigment epithelial dystrophy in Briard dogs.
AB  - The eyes of normal Briard dogs, Briards affected with inherited retinal pigment
      epithelial dystrophy (RPED) and a range of normal crossbred and beagle dogs were
      examined and the histopathology of RPED in the Briard was compared with the
      histopathological features of ageing in the normal canine retina. RPED was
      characterised by the accumulation of auto-fluorescent lipofuscin-like inclusions
      in the retinal pigment epithelium (RPE), which initially involved only non
      pigmented RPE cells overlying the tapetum but subsequently spread to all
      pigmented RPE cells. Secondary neuro-retinal degeneration was characterised by a
      gradual loss of the outer nuclear layer and the subsequent atrophy and
      degeneration of the inner retina. The loss of primary photoreceptors in the
      peripheral retina was accompanied by the migration of photoreceptor nuclei and
      appeared to resemble severe changes due to ageing. Intra-vitreal radiolabelled
      leucine was used to examine the rate of turnover of the outer segments of the
      rods in some Briards, but no significant variations were found. The activity of
      acid phosphatase in RPE was assayed in vitro and showed comparable regional
      variations in Briard and crossbred dogs. The results suggest that RPED in the
      Briard is unlikely to be due either to an increased rate of turnover of rod outer
      segments (and thus an increased phagocytic load) or to a primary insufficiency of
      lysosomal enzyme.

PMID- 8745250
TI  - Transfer of T-cell-mediated, antigen-specific delayed type hypersensitivity
      reactions to naive recipient inbred pigs.
AB  - Using inbred major histocompatibility complex-homozygous SLAb/b pigs, delayed
      type hypersensitivity (DTH) reactions against either intradermal tuberculin (PPD)
      or topical 2,4-dinitro-1-fluorobenzene (DNFB) were transferred specifically by
      the intravenous injection of approximately 6 x 10(8) blood lymphocytes kg-1
      bodyweight from donors sensitised, respectively, either with BCG or with DNFB
      into three-week-old piglets from an inbred litter. This antigen-specific,
      passively acquired sensitivity was revealed by three measures of DTH reactivity:
      first, macroscopic inflammation, which developed at the rate and intensity
      expected for actively acquired sensitivity to DNFB or PPD in older pigs;
      secondly, similarly enhanced local specific uptake of intravenously injected 51Cr
      labelled normal lymphocytes (more than 35-fold for each); and, thirdly,
      histological evidence of markedly increased local infiltration of CD45+
      lymphocytes and polymorphs, endothelial activation and the expression of adhesion
      molecules.

PMID- 8745251
TI  - Effect of nutritional level on bodyweight, degree of anaemia and carcase
      composition of sheep infected with Trypanosoma congolense.
AB  - The influence of nutritional level on the bodyweight, degree of anaemia and
      carcase composition of 24 sheep infected experimentally with Trypanosoma
      congolense was investigated. The infection caused a marked retardation of growth
      in the animals fed a low protein ration whereas the infected and control animals
      fed a high protein ration grew at similar rates. Both groups of infected animals
      developed similar degrees of anaemia but the infected group fed the high protein
      diet tended to sustain a higher intensity of parasitaemia than the group fed the
      low protein diet. The infection was also associated with low killing out
      percentages and a general reduction of total carcase protein, energy and fat. The
      decline in these carcase components was greater in the animals fed the low
      protein diet than in those receiving the high protein diet.

PMID- 8745252
TI  - Changes in the activities of hepatic xenobiotic metabolising enzymes after the
      administration of clenbuterol to female broilers.
AB  - Clenbuterol is a beta 2-agonist drug which in some countries is used illegally to
      enhance the productivity of various food-producing species, including poultry.
      This work investigated whether the prolonged exposure of female broilers to
      clenbuterol modified the activity of hepatic microsomal or cytosolic enzyme
      systems concerned with the metabolism of drugs, pesticides, carcinogens and
      endogenous substrates such as sexual steroids. Clenbuterol was added to the
      birds' diet at concentrations of 1 or 25 ppm for 21 days. There was a dose
      related decrease in the concentration of cytochrome P-450 and in the activities
      of the polycyclic aromatic hydrocarbon-inducible monooxygenases ethoxyresorufin O
      de-ethylase and aryl hydrocarbon hydroxylase. The activities of glutathione S
      transferase, N-acetyltransferase and uridinediphosphoglucuronyltransferase were
      not affected by the treatment.

PMID- 8745253
TI  - Comparative development of the antitrochanter in three strains of domestic fowl.
AB  - Lameness and musculoskeletal disease were more frequent in two strains of
      broilers (selected [S] and relaxed [R]) than in an unselected layer (J).
      Defective fibrocartilage accounted for 0.15 of the total area of antitrochanteric
      cartilage at 29 weeks of age in the S-strain birds. There was more retained
      hyaline cartilage in the R- and S-strain birds at 15 weeks, and at 22 and 29
      weeks there was delayed ossification. Occluded blood vessels, death of
      chondrocytes and degenerate areas of fibrocartilage occurred only in the broiler
      strains; they were worse in the S-strain and degenerate fibrocartilage occurred
      more frequently and in larger amounts. The area, length and depth of cartilage
      were larger in the heavier strains but the differences were considerably smaller
      than the difference in their relative bodyweights. The degeneration of the
      antitrochanter appeared to be associated with a reduction in the blood supply to
      the underlying hyaline cartilage and with the death of chondrocytes and the
      degeneration of matrix within the fibrocartilage of the antirochanter.

PMID- 8745254
TI  - Effect of cholagogues on the volume of the gallbladder of dogs.
AB  - The effect of cholagogues on the volume of the gallbladder was studied by two
      dimensional ultrasonography in six healthy dogs fasted for 24 hours. The volume
      was measured immediately before the administration of each test substance and at
      10-minute intervals for 120 minutes thereafter. Tap water administered orally as
      a control did not elicit significant contractions; only the normal cyclic
      contractions of the gallbladder, occurring at intervals of 60 to 90 minutes, were
      recorded. Magnesium sulphate (500 mg as a 20 per cent aqueous solution given
      orally) and clanobutin (15 mg kg bodyweight-1 given intravenously) reduced the
      volume of the gallbladder by 24 per cent, and the volume then gradually increased
      at a rate which was almost identical for the two drugs. The cholagogic hormone
      cholecystokinin (administered intravenously at a dose rate of 0.04 microgram kg
      bodyweight-1) reduced the volume of the gallbladder by 40 per cent 10 minutes
      after its administration, and the volume was still markedly decreased 30 to 50
      minutes after dosing. The results indicate that magnesium sulphate and clanobutin
      exert a direct effect on the motor activity of the gallbladder.

PMID- 8745255
TI  - Behaviour of a high-temperature-requirement A (HtrA) deletion mutant of Brucella
      abortus in goats.
AB  - Previous studies have shown that high-temperature-requirement A (HtrA) mutants of
      Brucella abortus are more sensitive to oxidative killing in vitro, are less able
      to survive in cultured murine macrophages and are attenuated in BALB/c mice. To
      measure the effect of an HtrA mutation on the virulence of B abortus in
      ruminants, pregnant goats in late gestation were exposed to infection by the
      conjunctival route with B abortus 2308 or an isogenic htrA mutant, PHE1.
      Infection with either 2308 or PHE1 resulted in abortion, but the serological
      responses to infection were consistent with 2308 but variable with PHE1. Strain
      2308 was recovered post mortem both from aborted fetuses and infected dams,
      whereas PHE1 was recovered from neither. Nevertheless, short term studies
      revealed that PHE1 could be recovered from infected goats for up to two weeks
      after infection, suggesting that although the HtrA mutation may change the
      colonising ability of B abortus, the virulence of the mutant in pregnant goats is
      not reduced.

PMID- 8745256
TI  - Evidence of asynchrony in the onset of signs of oestrus in zebu cattle treated
      with a progestogen ear implant.
AB  - Thirty-two zebu cows aged three to nine years were given a progestogen implant to
      determine their oestrous response. The experiment was carried out in two parts:
      in the first, 15 cows were induced to display oestrus, one animal per day during
      the dry season; in the second, 17 cows were selected for daily induction during
      the wet season. The animals were observed continuously from 24 hours after the
      removal of the first implant until 48 hours after the withdrawal of the last.
      There were no significant differences between the durations of the pre-receptive
      phase (pro-oestrus), receptive phase (oestrus) and post-receptive phase
      (metoestrus) in the two trials. The average expression of oestrus after the
      withdrawal of the implant was 60 per cent in the dry season and 35.2 per cent in
      the wet season (P < 0.05). Furthermore, only 60 per cent of the animals responded
      by displaying sexual activity within the expected range of 31 to 57 hours after
      withdrawal of the implant. The distributions of the animals displaying sexual
      behaviour in the wet and the dry seasons were similar. It is suggested that zebu
      cows under field conditions tend to manifest synergistic sexual behaviour.

PMID- 8745257
TI  - Myoelectrical activity of the gastrointestinal tract of sheep analysed by
      computer.
AB  - The myoelectrical activity of several sections of the digestive tract of sheep
      has been studied as an estimation of the gastrointestinal motility.
      Nickel/chromium electrodes were implanted chronically in the reticulum, rumen,
      omasum, antrum and duodenum. The myoelectrical signals were then recorded
      simultaneously and stored in a computer which calculated the integrated activity,
      duration and period (interval) of each separate reticuloruminal spike burst and
      the integrated activity (over one minute intervals) in the omasum, abomasum and
      duodenum. The different electromyographic parameters were standardised in sheep
      during a period of non-ingestion (resting period), and the physiological changes
      in these parameters associated with rumination and feeding were measured. The
      main effect induced by rumination was an increase in the myoelectrical parameters
      in the reticulum. Feeding enhanced the total activity in all regions studied. In
      the reticulorumen this increase was due to a rise in the frequency of the spike
      bursts, although there was a decrease in the integrated activity and duration of
      each individual spike burst.

PMID- 8745258
TI  - Infectivity of a Cryptosporidium species isolated from a domestic cat (Felis
      domestica) in lambs and mice.
AB  - Two neonatal lambs were inoculated orally with purified Cryptosporidium species
      oocysts isolated from a farm cat. Oocysts first appeared in the faeces of the two
      lambs three and 10 days after infection. Two distinct sizes of oocysts were
      observed in the faeces of both the cat and the lambs, the smaller measuring
      approximately 5.0 x 4.5 microns and the larger measuring approximately 6.0 x 5.0
      microns in diameter. The smaller type predominated. Histological examination of
      the alimentary tract of the lambs revealed endogenous stages of Cryptosporidium
      in the epithelial borders of the ileum. In addition, Cryptosporidium oocysts were
      detected in impression smears from the jejunum, ileum, caecum and colon.
      Suspensions of 10(3) oocysts from the faeces of the farm cat were inoculated into
      each of 10 newborn mice and 10(4) oocysts from the two experimentally infected
      lambs were inoculated into each of 20 newborn mice. Cryptosporidium oocysts were
      detected in gut homogenates from 19 of the 20 mice inoculated with oocysts from
      the lambs but in none of the mice inoculated with oocysts from the cat.

PMID- 8745259
TI  - Experimental single and trickle infections of cattle with Taenia saginata:
      studies of immunodiagnosis.
AB  - Two groups of 12 calves were given either a single infection dose of 30,000
      Taenia saginata eggs (group A) or trickle infected with 12 x 2500 T saginata eggs
      (group B). The calves were killed 16, 22 or 54 weeks after infection and the
      numbers of viable and dead parasites were counted by slicing selected organs and
      muscles of half of the carcases. The total numbers of cysts and the numbers of
      viable cysts were higher in group A than in group B. Within the two groups there
      were no significant differences between the numbers of cysts at the three dates
      of slaughter. Comparable results were obtained by using an ELISA and a dot blot
      procedure for the detection of antibody in the serum of the infected calves; an
      initial increase in response during the first 10 weeks after infection was
      generally followed by a gradual decline. When using a monoclonal antibody-based
      ELISA for the detection of circulating antigens, the sera from all the 14 animals
      which had no viable cysts or only dead cysts at slaughter did not react with the
      monoclonal antibodies. Calves 122 and 123, which harboured two and 122 viable
      cysts, respectively, reacted positively during the late phase of the infection to
      the antigen-detecting ELISA. However, several other animals which harboured
      between two and 41 viable cysts at slaughter did not react.

PMID- 8745260
TI  - Distribution of calcitonin gene-related peptide, vasoactive intestinal
      polypeptide, neuropeptide Y, substance P and dopamine beta-hydroxylase
      immunoreactive nerve fibres in the trachea of sheep.
AB  - The distribution of nerve fibres containing calcitonin gene-related peptide
      (CGRP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), substance
      P (SP) and the catecholamine enzyme marker dopamine beta-hydroxylase (DBH) in the
      trachea of sheep was investigated by immunohistochemical methods. A semi
      quantitative assessment of the extent of the nerve fibres immunoreactive for the
      various antigens was also made. Moderate to large numbers of CGRP-like
      immunoreactive (CGRP-Li) nerve fibres were present in all parts of the trachea
      including the epithelial layer, lamina propria, smooth muscle, closer to the
      mucous glands and blood vessels, and in the elastic fibre connective tissue
      layer. Although SP-Li nerve fibres had a similar distribution to CGRP, they were
      absent from the epithelial layer and only small numbers of fibres were present in
      other areas. Moderate numbers of VIP-Li fibres were present in the smooth muscle
      and close to mucous glands and blood vessels. Moderate numbers of NPY-Li fibres
      were present in the smooth muscle with smaller numbers close to mucous glands and
      blood vessels. Large numbers of DBH-Li nerve fibres were present in the smooth
      muscle and they had a similar distribution to NPY. The presence of both NPY and
      DBH in most DBH-Li nerve fibres was established by a double-straining technique,
      but not all the DBH-Li fibres contained NPY. The DBH/NPY-Li nerve fibres in the
      smooth muscle formed an extensive and dense interconnecting network and were the
      most common types of nerve fibres observed.

PMID- 8745261
TI  - Characterisation of murine monoclonal antibodies recognising opsonic, mouse
      protective, chaining and mucosally relevant epitopes on the M protein of
      Streptococcus equi subspecies equi.
AB  - Six hybridomas secreting murine monoclonal antibodies (mAbs) specific for the M
      protein of Streptococcus equi subspecies equi were characterised. The mAbs
      recognised the major 41 and 46 kDa fragments of M protein in an acid extract of S
      equi and the 56 and 58 kDa dimer of the native molecule in a mutanolysin extract,
      but did not react with recombinant M-like protein of S equi subspecies
      zooepidemicus. One mAb (2A10) showed strong opsonic activity for S equi and
      protected mice against an experimental challenge with virulent S equi. Two other
      mAbs were mouse-protective but not opsonic. All the mAbs elicited a strong
      chaining response from S equi, but had only a weak chaining effect on a strain of
      S equi (19) that expressed only 4 per cent of the normal amount of M protein.
      Antibodies in nasopharyngeal mucus of horses recently recovered from strangles
      were inhibited to different extents by each mAb. These different functional
      behaviours and the result of inhibition ELISAs suggest that the M protein of S
      equi carries multiple epitopes.

PMID- 8745262
TI  - Immunocytochemical detection of growth factors (PDGF and TGF beta) in equine
      chronic pneumonia.
AB  - The roles played by platelet-derived growth factor (PDGF) and transforming growth
      factor beta (TGF beta) in the development of pulmonary fibrosis in equine chronic
      pneumonia varied greatly. Macrophages, epithelial cells and fibroblasts were
      identified as a source of PDGF, the principal role of which was related to its
      mitotic effect on epithelial cells, and particularly on fibroblasts in the final
      phase of the disease. TGF beta was detected in epithelial cells in all three
      phases of the disease and in fibroblasts in the last phase. However, the role of
      TGF beta in this pulmonary disease is not clear because its expression in the
      cytoplasm of fibroblasts in areas of strong collagenation during the last phase
      was weak. Nonetheless, it was responsible for the production and release of
      collagen during the stage of total fibrosis.

PMID- 8745263
TI  - Quantitative determination of bovine serum haptoglobin in experimentally induced
      Escherichia coli mastitis.
AB  - A high performance liquid chromatography (HPLC) method was developed, validated
      and used to analyse haptoglobin concentrations in serum samples taken from eight
      cows which had been challenged twice intramammarily with Escherichia coli. The
      results of the HPLC were compared with those from a photometric assay. The
      kinetics of the haptoglobin response were analysed with pharmacokinetic computer
      software. In contrast with the photometric assay, the HPLC was sufficiently
      sensitive to detect normal background levels of bovine serum haptoglobin. The
      serum haptoglobin concentrations of healthy cows ranged from 22 to 47 mg litre-1.
      As the concentration of haptoglobin increased, the results of the two methods
      correlated well (r = 0.96). A 52-fold increase in serum haptoglobin was detected
      after the first challenge with E coli. The mean pharmacokinetic parameters of the
      response after the first challenge were: lag phase 12 hours, t2/1increase 20
      hours, tmax 72 hours, t1/2decrease 46 hours, and mean residence time 112 hours.
      The second challenge three weeks later resulted in a significantly lower
      haptoglobin response, the area under curve being 35 per cent of that after the
      first challenge. The clinical signs and inflammatory changes in the milk did not
      differ significantly between the challenges.

PMID- 8745264
TI  - Use of sheep maintained by intragastric infusion as a model for studying the
      endogenous loss of phosphorus in ruminants.
AB  - Mature sheep fitted with a rumen cannula and an abomasal catheter were used to
      evaluate whether sheep maintained by intragastric infusion could be used as a
      model for studying minimum endogenous phosporus loss in ruminants. In control
      periods the sheep received 1.29 g phosphorus day-1 by infusion and maintained
      phosphorus balance. The withdrawal of phosphorus from the infusate led to a
      reduction in the excretion of phosphorus to 6.4 mg kg liveweight-1 day-1, a level
      lower than that currently used to estimate maintenance phosphorus requirements.
      However, salivary phosphorus secretion, based on rumen phosphorus outflow,
      averaged only about 1.2 g day-1, a level which would be considered insufficient
      to meet rumen microbial requirements in a normally fed animal. Allowing the sheep
      access to a small amount of roughage, although contributing little additional
      phosphorus, greatly increased salivary phosphorus flow and increased their
      endogenous excretion of phosphorus to levels close to those used to estimate
      maintenance requirements. These results suggest that this technique may offer an
      alternative way of measuring minimum endogenous mineral loss to those currently
      in use.

PMID- 8745265
TI  - Demonstration by reverse transcription-polymerase chain reaction of multiple
      cytokine mRNA expression in bovine alveolar macrophages and peripheral blood
      mononuclear cells.
AB  - The expression of the mRNAs of the cytokines interleukin (IL)-1 alpha, IL-1 beta,
      IL-2, IL-4, IL-6, interferon (IFN) gamma, tumour necrosis factor (TNF) alpha, and
      granulocyte-macrophage colony-stimulating factor (GM-CSF) was demonstrated by the
      reverse transcription-polymerase chain reaction (RT-PCR) in bovine alveolar
      macrophages (AMs) and peripheral blood mononuclear cells (PBMCs). By the use of
      the RT-PCR, a specific and highly sensitive technique has been developed to
      analyse simultaneously the array of cytokine messenger RNAs in bovine AMs and
      PBMCs. AMs stimulated with lipopolysaccaride (LPS) for four hours in vitro
      expressed IL-1 alpha, IL-1 beta, IL-6, TNF alpha and GM-CSF; PBMCs stimulated
      with LPS for four hours expressed IL-1 alpha, IL-1 beta, IL-6, TNF alpha and GM
      CSF and when stimulated with concanavalin A (ConA) expressed IL-2, IL-4, IFN
      gamma and GM-CSF efficiently.

PMID- 8745266
TI  - Gonadotropin-releasing hormone (GnRH) neurons of the developing tectum of the
      mouse.
AB  - Using a modified immunocytochemistry protocol with enhanced sensitivity, we were
      able to visualize a population of neurons in the tectum of the developing mouse
      that contained GnRH-like immunoreactivity. In microscopic studies conducted using
      100 microns sections cut in sagittal or horizontal planes, 10-20 lightly-stained
      neurons were first detected in the tectum at E13.75 (morning of plug = E0.5). The
      number of immunostained cells increased exponentially reaching a peak at E15.75
      before decreasing in number. No positive neurons were seen in the tectum at PN20
      or later. The GnRH cells were located medially along the dorso-ventral axis of
      the tectum in a region of the brain distinct from that containing GnRH neurons
      that migrate into the CNS from the olfactory placode. To determine the nature of
      the immunoreactivity, two approaches were used. Analysis of tissue from an hpg
      mutant strongly supports the hypothesis that these cells make mammalian GnRH.
      Immunocytochemical data suggest that although the precursor protein is
      synthesized, the cleaved and amidated decapeptide may be absent or be present at
      an undetectable level. Our results demonstrate that in addition to the GnRH
      neurons from the placade, a population of GnRH neurons exists in the mouse
      tectum. This population is developmentally regulated, appearing only during
      embryonic and early postnatal ages but not in the adult.

PMID- 8745267
TI  - Regulation of pituitary vasopressin V1b receptor mRNA during stress in the rat.
AB  - Previous studies have shown a parallel relationship between pituitary vasopressin
      (VP) receptor content and responsiveness of the corticotroph during chronic
      stress. The regulation of pituitary VP receptors was further studied by analysis
      of V1b VP receptor mRNA levels in pituitaries of rats subjected to chronic
      immobilization, i.p. hypertonic saline injection (physical stress paradigms
      associated with increased pituitary responsiveness), and water deprivation, or to
      2% saline in the drinking water (osmotic stress paradigms associated with
      decreased pituitary responsiveness). Northern blot hybridization with a 363 bp
      32P-labelled fragment of the rV1b receptor cDNA coding sequence revealed two
      bands of about 3.7 and 3.2 Kb, whereas a probe directed to the 5' untranslated
      region recognized only the 3.7 Kb band. Repeated i.p. hypertonic saline
      injection, 3 times in 24 h at 8 h intervals, or daily for 8 days, increased the
      intensity of the 3.7 Kb band by 155 +/- 17.5% (P < 0.01) and 118 +/- 14.6% (P <
      0.01), respectively, while the 3.2 Kb band increased by 122 +/- 39.3% (P < 0.01)
      only after 3 times injection. Smaller increases of 39 +/- 11 and 33 +/- 9% (P <
      0.05) in the 3.7 Kb band were found after repeated immobilization 3 times in 24 h
      and 2 h for 8 days respectively. In situ hybridization studies confirmed
      significant increases (P < 0.05) in V1b receptor mRNA levels after 8 and 14 days
      repeated immobilization (63 +/- 19% and 83 +/- 10%) or i.p. hypertonic saline
      injection (110 +/- 13% and 73 +/- 20%). In response to acute stress, V1b receptor
      mRNA increased by 77 +/- 5% (3.7 Kb band) after 4 h immobilization for 1 h,
      whereas both bands were reduced by 49 +/- 5% and 45 +/- 5%, 4 h after a single
      i.p. hypertonic saline injection. The decrease in V1b receptor mRNA following a
      single i.p. hypertonic saline injection was prevented by pretreatment with a V1
      receptor antagonist, suggesting that increased VP secretion may account for this
      effect. In spite of the decrease in V1b receptor mRNA following i.p. hypertonic
      saline injection, VP binding in pituitary membrane rich fractions, and VP
      stimulated inositol phosphate formation in quartered hemipituitaries were
      increased by 24 and 39%, respectively. V1b receptor mRNA levels were unchanged or
      decreased following prolonged osmotic stimulation. These studies suggest that
      increased V1b receptor mRNA levels contribute to the VP receptor upregulation
      observed during repeated immobilization and i.p. hypertonic saline injection,
      whereas the lack of parallelism between V1b receptor mRNA and VP binding
      indicates that regulation of steady-state levels of V1b receptor mRNA is not a
      primary determinant in the control of pituitary VP receptor concentration during
      stress.

PMID- 8745268
TI  - The effect of pentobarbital on the electrical activity of LHRH pulse generator in
      the ovariectomized rat with or without estrogen priming.
AB  - Effects of pentobarbital sodium (PB) on the electrical activity of LHRH pulse
      generator were investigated in the ovariectomized (OVX) rat fitted with
      chronically implanted electrode arrays in the arcuate-median eminence region of
      the hypothalamus. PB was injected intraperitoneally (i.p.) at a dose of 32 mg/kg
      bw, which has blocked the surge of LH secretion when injected at 13.45 on the day
      of proestrus, presumably by blocking the activity of the LHRH surge generator.
      After i.p. injection of PB, the first characteristic increase (volley) in the
      hypothalamic multiunit activity (MUA), each of which was associated with the
      initiation of an LH pulse, appeared at the mean interval of 42 min, which was
      significantly greater than the value, 30 min, in the rat given i.p. injection of
      saline. The second and third MUA volleys appeared, however, at similar intervals
      to those in rats given saline. There were no significant changes in the amplitude
      of LH pulses which followed. In the OVX rat implanted with a silastic tube packed
      with estradiol-benzoate (E2) for 1 day, MUA volleys were unclear, mingled with
      high background activities, but clear volleys appeared after PB injection. The
      mean interval of LH pulses in the rat given i.p. injection of saline was 51 min,
      by 24 min longer than the value in the E2-unimplanted OVX rat. But, after PB
      injection, the 1st LH pulse appeared at the interval of 37 min, which was by 25
      min smaller than that after saline and the overall mean of 3 intervals was 34
      min, showing a significant shortage. No PB effect was seen in the LH pulse
      amplitude in the E2-implanted OVX rat. The presults show that the LHRH pulse
      generator is much more resistant to PB than the surge generator in the OVX rat
      either with or without estrogen priming, and in the rat with estrogen priming,
      the pulse generator is rather activated by PB.

PMID- 8745269
TI  - LHRH pulse generator is stimulated by naloxone in the pentobarbital-blocked
      proestrous rat.
AB  - Previous studies by us and others led us to hypothesize that there are separate
      LHRH pulse and surge generators in the rat brain. The present study was designed
      to detect the activity of LHRH pulse generator by checking changes in LH
      secretion and the multiunit activity (MUA) of the arcuate-median eminence region
      of the hypothalamus during infusions of naloxone (NAL, 2 mg/h) in the proestrous
      rat in which the LHRH surge generator activity was blocked by pentobarbital
      sodium (PB, 32 mg/kg bw, ip). The animals were subjected to blood sampling in the
      morning (1000-1300 h) or afternoon (1400-1700), and injected with PB at 09.45 or
      13.45, respectively. During saline infusions in the rat given PB injection at
      either 09.45 or 13.45, serum LH levels were low but fluctuated significantly,
      suggesting a pulsatile secretion in either the morning or the afternoon period.
      The pulse intervals were an average 28.2 min in the morning and 42.2 min in the
      afternoon. NAL infusions decreased the pulse interval significantly, to 22.0 min
      in the morning and to 27.0 min in the afternoon. In the electrophysiological
      experiment, characteristic increases in the MUA (volleys), which occur in
      association with the initiation of an LH pulse and therefore are considered to
      represent an increased activity of the LHRH pulse generator, appeared during NAL
      (5 mg/h) infusions in either the morning or the afternoon. These results strongly
      suggest that separate LHRH pulse and surge generators exist in the brain, and
      that, even during the critical period of proestrus, the activity of LHRH pulse
      generator is disclosed by PB, which, on the other hand, arrests the surge
      generator.

PMID- 8745270
TI  - ACTH-suppressive and vasodilator actions of adrenomedullin in conscious sheep.
AB  - Adrenomedullin (ADM) is a 52 amino-acid peptide which is a potent vasodilator in
      rats, and suppresses basal and CRF-induced ACTH release from cultured pituitary
      cells. The present study examines the hemodynamic and hormonal actions of human
      ADM (1-52) infusion in conscious, chronically instrumented sheep. Five sheep were
      infused intravenously (IV) or intracerebroventricularly (ICV) with ADM at 100
      micrograms/h for 60 min, and mean arterial pressure (MAP), heart rate (HR),
      cardiac output (CO), stroke volume (SV), total peripheral conductance (TPC),
      coronary blood flow (CF), coronary conductance (CC), peak aortic flow (Fmax), and
      left ventricular dF/dt were monitored by a computer-based data collection system
      every 2 min. Plasma concentrations of adrenocorticotropin (ACTH), arginine
      vasopressin (AVP) and renin were measured after 60 min of infusion. IV ADM
      produced a small fall in MAP of 3 +/- 1 mmHg, associated with a reflex increase
      in HR of 14 +/- 3 b/min. CO increased by 1.3 +/- 0.3 l/min, whereas SV remained
      unchanged. TPC was markedly increased by 20 +/- 3 ml/min/mmHg. Changes in CF were
      also seen with an increase of 10 +/- 2 ml/min, and CC increased in parallel by
      0.15 +/- 0.02 ml/min/mmHg. Fmax and dF/dt showed small increases of 2.1 +/- 0.5
      l/min and 85 +/- 20 l/min/sec respectively. Plasma concentrations of ACTH and
      cortisol were reduced by 58% and 55% respectively, whereas plasma renin
      concentration increased by 106%. There was no change in plasma levels of AVP. ICV
      infusion of ADM had no effect on any parameter measured. These data suggest that
      systemic ADM produces a sustained vasodilator action to lower blood pressure in
      sheep, and this is the first study to report the ACTH-suppressor action of ADM in
      conscious animals. ADM may therefore be an important hormone involved in the
      regulation of pituitary/adrenal function, in addition to its cardiovascular and
      fluid regulatory actions in mammals.

PMID- 8745271
TI  - Localization of [125I]IGF-I binding on the ovine pars tuberalis.
AB  - In the sheep, it has been shown that the pars tuberalis of the pituitary may
      mediate the photoperiodic control of seasonal changes in prolactin secretion.
      High concentrations of melatonin receptors are present on the ovine pars
      tuberalis and melatonin is known to inhibit forskolin-stimulated cyclic AMP
      production in this tissue. Other hormonal inputs to the ovine pars tuberalis have
      not yet been identified. In the rat mRNA for the IGF-I receptor has been
      identified in the pars tuberalis using in situ hybridization. In order to define
      whether IGF-I may influence the function of the ovine pars tuberalis the presence
      of receptors for IGF-I has been investigated. Using in vitro autoradiography
      specific [125I]IGF-I binding was found in high concentrations over the ovine pars
      tuberalis particularly associated with certain of the capillaries. Homogenate
      receptor assays showed saturable specific binding of [125I]IGF-I with a mean
      dissociation constant (Kd) of 0.5 +/- 0.1 nM (n = 4). Competition studies
      revealed a rank order of potency of IGF-I > IGF-II > > > insulin, in displacing
      [125I]IGF-I binding, indicative of a mixed population of IGF-I and IGF-II/mannose
      6-phosphate receptors and insulin-like growth factor binding proteins (IGFBPs).
      Cross-linking of [125I]IGF-I to pars tuberalis membrane homogenates and analysis
      by SDS-PAGE under reducing conditions confirmed the presence of both IGF-I
      receptors and binding proteins. Autophosphorylation of a 97 kDa substrate,
      compatible with the beta-sub-unit of the IGF-I receptor, was increased in the
      presence of IGF-I, indicating the existence of functional IGF-I receptors on the
      ovine pars tuberalis. In contrast in the rat [125I]IGF-I binding was restricted
      to the median eminence region of the brain and was not detectable over the pars
      tuberalis.

PMID- 8745272
TI  - Localization of mRNA coding for the three subtypes of atrial natriuretic factor
      (ANF) receptors in rat anterior pituitary gland cells.
AB  - Atrial Natriuretic Factor (ANF) action is mediated by highly selective and
      specific receptors. Three subtypes have been characterized and cloned: ANF
      receptor-A, -B and -C. These subtypes are all expressed in the anterior pituitary
      of the rat. In the present study, the mRNA for each subtype was detected by in
      situ hybridization. The amounts of ANFR-A and -B mRNA were found to be similar,
      and to be twice that of ANFR-C mRNA. At the ultrastructural level, the three
      types of ANFR mRNA were expressed in three anterior pituitary cell types, namely
      lactotrophs, corticotrophs, and gonadotrophs, identified by their hormonal
      content. No signal was revealed in somatotrophs or thyrotrophs. The different
      forms of mRNA were similar in terms of subcellular localization: in the
      cytoplasmic matrix and the nuclear euchromatin. These data indicate that the
      anterior pituitary is an important target tissue for ANF action.

PMID- 8745273
TI  - Evidence for a regulatory role of melatonin on serotonin release and uptake in
      the pineal gland.
AB  - Melatonin has been proposed to exert some regulatory actions within the pineal
      gland itself. The present study examined the effect of melatonin on the release
      of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) from rat pineal
      glands by using an in vitro perifusion system. Melatonin induced a concentration
      dependent stimulatory effect on 5-HT secretion from 10(-6) M to 10(-3) M. Maximal
      effects were obtained with melatonin 10(-3) M and concentrations lower than 10(
      6) M were without effect. The secretion of 5-HIAA was inhibited by melatonin 10(
      3) and 10(-4) M, but it was increased when pineals were incubated with 10(-5) and
      10(-6) M of melatonin. The indoleamine secretion was also studied on peripherally
      denervated rat pineal glands. Basal output of 5-HT from these glands was
      increased when compared with those from control rats. In contrast, the secretion
      of 5-HIAA was strongly reduced after removal of the sympathetic input to the
      pineal gland. Melatonin 10(-3) M failed to stimulate 5-HT release from denervated
      pineal glands, although it inhibited 5-HIAA secretion. In contrast, melatonin 10(
      5) M enhanced 5-HT release without altering 5-HIAA output. Fluoxetine, a 5-HT
      uptake inhibitor, produced similar effects than mM concentrations of melatonin on
      the indoleamine secretion from control pineal glands, but it had no effect on
      glands taken from peripherally denervated rats. These data suggest that mM
      concentrations of the pineal hormone are able to stimulate 5-HT release from the
      pinealocyte, while mM concentrations of melatonin increase extracellular 5-HT by
      inhibiting its reuptake in the adrenergic nerve endings. These findings are
      discussed in relation to the possible role of melatonin regulating the intra- and
      extracellular availability of 5-HT in the pineal gland and its significance as an
      autocrine factor.

PMID- 8745274
TI  - Dexamethasone regulates the expression of neuronal properties of a rat insulinoma
      cell line.
AB  - Insulin producing cells of the pancreas (beta cells) and neuronal cells share a
      large number of similarities. For example, different molecules, thought to be
      specific of neuronal cells, are expressed by beta cells. The factors regulating
      the expression of these molecules in beta cells are poorly understood. In the
      present work, we have studied the effect of dexamethasone, a synthetic
      glucocorticoid, on the expression of three different neuronal traits expressed by
      INS-1 cells, a highly differentiated beta cell line. We demonstrate that
      dexamethasone treatment decreases the steady state levels of mRNAs coding for
      both the low- and the high-affinity NGF receptors and of mRNA coding for NF-H, an
      intermediate neurofilament specific of neurons. This effect was time-dependent,
      the decrease being detectable after 4-8 h treatment. The decrease in NGF
      receptors mRNAs steady state levels was paralleled by a decrease in the number of
      NGF binding sites as demonstrated after Scatchard analysis. We further focused on
      the mechanisms by which dexamethasone affects the expression of the low affinity
      NGF receptor. The effect is countered by the glucocorticoid antagonist RU486,
      indicating that it is mediated by the glucocorticoid receptor. Finally, the
      decrease in the low-affinity nerve growth factor receptor mRNA steady state level
      after dexamethasone treatment is not due to mRNA destabilization but can be
      rather explained through a change in gene transcription.

PMID- 8745275
TI  - Static and dynamic actions of cytoplasmic Ca2+ in the adaptation of responses to
      saturating flashes in salamander rods.
AB  - 1. In order to study the relative contribution to light adaptation of the various
      actions of Ca2+ in rod photoreceptors, changes in cytoplasmic calcium
      concentration ([Ca2+]i) were opposed by manipulating the calcium fluxes across
      the outer segment membrane at different times during the response to a bright
      flash. 2. When the outer segment was superfused with 0 Ca2+, 0 Mg2+,0 Na+
      solution just before a bright flash, the period of response saturation was
      greatly prolonged. But if instead the solution change was made at progressively
      increasing times after the flash, the delay before the response recovered from
      saturation declined exponentially towards its value in Ringer solution with a
      time constant of around 1 s. In contrast, recovery time was little affected by
      stepping to 0 Ca+,0 Mg2+,0 Na+ solution before the flash and returning to Ringer
      solution shortly before the normal time of recovery from saturation. 3. When a
      bright flash was delivered just before the extinction of steady light, the
      response recovered from saturation progressively earlier as this steady intensity
      was increased. If, instead, the outer segment was transferred to 0 Ca2+,0 Mg2+,0
      Na+ solution just before the bright flash then the time spent in saturation by
      the response was prolonged in darkness, but this additional delay progressively
      decreased as the steady intensity increased. 4. These results are consistent with
      the notion that the light-induced reduction of the time spent in saturation by
      the bright flash response in Ringer solution resulted from the static decrease in
      [Ca2+]i induced by the background, while the additional delay in the recovery
      from saturation when further changes in [Ca2+]i were prevented stemmed from the
      abolition of the dynamic fall in [Ca2+]i during the flash response. 5. Analysis
      of the effects of steady light on the time spent in saturation by the bright
      flash response under these conditions suggests that actions of [Ca2+]i at, or
      soon after, the time of the flash are largely responsible for the graded changes
      which take place in the bright flash response during light adaptation, while
      rapid actions of [Ca2+]i at the time of response recovery also play a role in the
      adaptation of the steady response to background light itself. 6. These data have
      been interpreted in terms of differential actions of [Ca2+]i on 'early' stages
      (e.g. events leading to phosphodiesterase activation) and 'late' stages (e.g.
      guanylyl cyclase) in the transduction mechanism. A quantitative model is
      presented which suggests that actions of [Ca2+]i on 'late' stages play a
      proportinately larger role in background adaptation than actions on 'early'
      stages.

PMID- 8745276
TI  - A novel tetrodotoxin-resistant sodium current from an immortalized
      neuroepithelial cell line.
AB  - 1. Voltage-gated ionic currents were recorded from cells of an immortalized
      neuroepithelial cell line named V1. The cell line was produced by insertion of
      the temperature-sensitive tsA58 allele of the SV40 large T-antigen into embryonic
      day 14 mouse hypothalamic cells. V1 cells display a mixed immature neural-glial
      phenotype and have two phenotypes, round and flat. 2. Recordings from round V1
      cells demonstrate voltage-gated Na+ and K+ currents (n = 297), while no voltage
      gated currents were observed in flat V1 cells (n = 45). Voltage-gated currents
      were recorded from cells cultured at both permissive and restrictive
      temperatures. 3. Internal Cs+ and external tetraethylammonium (TEA) were used to
      suppress outward currents. The remaining inward current has rapid activation and
      inactivation time constants which decreased as the test potential increased. In
      different cells, the amplitude of the peak inward current varied from about 50 pA
      to as large as 4500 pA (in 120 mM external Na+). The reversal potential for the
      inward current was close to the predicted Nernst equilibrium potential for Na+.
      Both the magnitude and reversal potential of the inward current were dependent on
      the external Na+ concentration. It is therefore considered to be a Na+ current,
      INa. 4. INa was found to be TTX resistant. About 5% of the INa was blocked by 200
      nM TTX and 20 microM TTX fully suppressed the Na+ current. The apparent Kd for
      TTX blockade was estimated to be 1.49 microM. 5. The activation kinetics of INa
      could be described by a Hodgkin-Huxley model with an m3 variable. The time
      constants of activation and inactivation of INa are fast, similar to those of the
      TTX-resistant and TTX-sensitive Na+ currents in central nervous system neurons
      and glial cells. 6. The divalent and trivalent cations Cd2+, Co2+, Ni2+, Zn2+ and
      La3+ shifted the activation of INa to more positive potentials and decreased the
      maximal conductance in a dose-dependent manner. The apparent Kd values for
      blockade of the INa by Cd2+, Co2+, Ni2+, Zn2+ and La3+ were 430, 3500, 1900, 83
      and 202 microM, respectively. 7. The addition of phorbol myristate acetate, an
      activator of protein kinase C, consistently produced a reduction in the
      amplitudeof INa without affecting the time course of activation or inactivation.
      8. INa in V1 cells expresses a unique combination of voltage and time kinetics
      and sensitivity to blockade by TTX and cations. We hypothesize that this Na+
      current may be expressed transiently during development of the central nervous
      system at the stage of development represented by the V1 cell line.

PMID- 8745278
TI  - Sodium--potassium pump current in rabbit sino-atrial node cells.
AB  - 1. The Na(+)-K+ pump current (Ip) was studied in sino-atrial (SA) node cells of
      rabbits using the whole-cell patch-clamp technique. 2. With 50 mM Na+ in the
      pipette solution ([Na+]pip), changing the external K+ concentration (-K+-o) from
      0 to 5.4 mM caused the holding current to shift in an outward direction and reach
      a new steady state. The current-voltage relationships obtained by subtraction of
      current traces recorded at 0 mM Ko+ from those recorded at 5.4 mM Ko+ revealed
      time-independent and voltage-dependent characteristics. The external K(+)-induced
      current was completely blocked by external application of 10 microM ouabain,
      indicating the existence of Ip in SA node cells of rabbit heart. 3. Ip increased
      as [K+]o increased. With 30 mM Na+pip, Ip at 0 mV was activated by [K+]o with non
      linear least-squares fit parameters for the Hill equation of K0.5 of 1.4 mM and a
      Hill coefficient (nH) of 1.2 (n = 7). 4. The cation dependence of the K+ site of
      the Na(+)-K+ pump was examined using various monovalent cations. The sequence was
      K+ > or = Rb+ > Cs+ > > > Li+. 5. Ip at 0 mV also increased as [Na+]pip was
      increased from 10 to 150 mM at 5.4 mM Ko+, with a K0.5 value of 14 mM and a nH of
      1.3 (n = 54). 6. Ip at 0 mV was reduced by lowering the temperature from 37 to 25
      degrees C with 30 mM Na+pip and 5.4 mM Ko+. The temperature coefficient (Q10) for
      Ip was 2.1 (n = 27). 7. With 10 mM Na+pip and 5.4 mM Ko+, the half-activation
      voltage of Ip was -52 +/- 16 mV and the current at this voltage was 22.5 +/- 3.5
      pA (n = 10), indicating that Ip contributes significantly to the background
      outward current during the normal pacemaker potential of SA node cells.

PMID- 8745277
TI  - Intracellular acidification reduced gap junction coupling between immature rat
      neocortical pyramidal neurones.
AB  - 1. Developmental changes in electrophysiological properties of pyramidal neurones
      correlated with the developmental decline in gap junction-dependent dye coupling
      were investigated in coronal slices of rat prefrontal and sensorimotor cortex.
      Effects of intracellular acidification induced by application of weak organic
      acids on neuronal dye coupling, electrotonic parameters as well as synaptic
      potentials were examined using the patch clamp technique. Optical monitoring of
      intracellular pH revealed an acidic shift of 0.4-0.5 pH units following sodium
      propionate application. 2. Dye coupling between layer II-III neurones was
      prominent during the first two postnatal weeks. During this period, pre
      incubation of slices with 30 mM of the sodium salts of weak organic acids reduced
      the number of cells coupled to the injected neurones by 64%. 3. Between postnatal
      days 1 and 18, the mean neuronal input resistance decreased significantly (by
      81.0%). Both the membrane time constant (tau 0) and the first equalizing time
      constant (tau 1) also showed a significant developmental decline of 25.8 and
      65.8%, respectively. Electrotonic length decreased by 34.9%. The
      electrophysiological properties of neurones displayed a pronounced intercellular
      variability which decreased with on-going development. 4. During the first two
      postnatal weeks, intracellular acidification led to a mean increase in neuronal
      input resistance of 55.9% and a mean decreae in electrotonic length of 22.2%. The
      membrane time constant was reduced by approximately 25% in the majority of
      neurones tested. Significant electrophysiological effects induced by
      intracellular acidification were not detected in uncoupled neurones from 18-day
      old rats. 5. EPSP width at half-maximal amplitude showed a substantial reduction
      of approximately 50%, while rise times of the non-NMDA receptor-mediated EPSP
      components displayed no significant change during development. Both weak organic
      acids, as well as the gap junction blocker 1-octanol, reduced excitatory synaptic
      transmission independent of developmental age. 6. We conclude that gap junction
      permeability is regulated by intracellular pH in developing layer II-III
      pyramidal cells in the rat neocortex. The prominent correlation between pH
      induced reduction in dye coupling and changes in electrophysiological cell
      properties suggests a significant influence of gap junctions on synaptic
      integration and information transfer in the immature neocortex.

PMID- 8745279
TI  - Whole-cell K+ currents in identified olfactory bulb output neurones of rats.
AB  - 1. Voltage-gated whole-cell K+ currents have been investigated in olfactory bulb
      (OB) output (mitral/tufted) neurones from neonatal rats, which were retrogradely
      labelled by rhodamine or Fast Blue and identified after enzymatic dissociation.
      Forty-five per cent of labelled neurones exhibited either phasic or non-phasic
      spontaneous firing in cell-attached configuration. 2. Four outward K+ currents
      have been identified in all such identified OB output neurones. They are the
      transient (IA), the delayed rectifier (IDK), and two Ca(2+)-dependent (IK(Ca))
      currents. No inward rectifier was detected. 3. The IA was activated at around -45
      mV and reached its peak within 3-10 ms. The decay phase could be described by
      single exponential distribution with the time constant of 45.2 +/- 3.8 ms at
      depolarizations 10-60 mV from a holding potential of -70 mV. Its activation and
      steady-state inactivation processes could be fitted with Boltzmann equations
      yielding half-maximal activation potentials of 7.6 +/- 0.4 and -47.4 +/- 0.2 mV,
      respectively. It was sensitive to block by 4-AP (1 mM) and by Zn2+ (1 mM). 4. The
      IDK was activated at potentials more positive than -30 mV, with half-maximal
      activation at 21 mV. It was sustained during 1 s test pulses without apparent
      decay. It was blocked by TEA at a concentration of 20 mM. About 8% of the
      sustained current, in 11/24 cells tested, was found to resist block by a
      combination of all pharmacological agents tested. 5. Apamin at 100 nM blocked a
      TEA-insensitive component which accounted for about 23% of the maximal sustained
      currents. Iberiotoxin (IbTX), which has been found to block maxi K+ currents more
      selectively than does charybdotoxin, reversibly blocked Ca(2+)-activated K+
      current, with a half-maximal dose of about 100 nM in 8/13 OB output neurones
      tested. This accounted for 20% of the maximal sustained K+ current. The effect of
      IbTX was not observed in the presence of 20 mM external TEA. 6. Direct evidence
      is provided in this study regarding kinetic and pharmacological properties of
      four types of outward K+ channels in OB output neurones.

PMID- 8745280
TI  - Characteristics of type I and type II K+ channels in rabbit cultured Schwann
      cells.
AB  - 1. Voltage-dependent K+ currents were studied in rabbit Schwann cells cultured
      from neonatal sciatic nerve and from the lumbar or sacral spinal roots of 10-day
      old animals. 2. Whole-cell K+ currents, evoked in response to depolarizing
      voltage-clamp steps, were categorized as type I or type II on the basis of their
      apparent threshold and activation kinetics. In the presence of a quasi
      physiological [K+] gradient, the magnitude of the fully activated type I current
      varied linearly with membrane potential, whereas type II current always gave rise
      to a curved and outwardly rectifying current-membrane potential (I-E) relation.
      3. Type II whole-cell currents, obtained with long duration voltage-clamp steps
      (> or = 1 s), have an apparent threshold for activation close to -40 mV. Type II
      current inactivated slowly, and apparently to completion. The current is more
      than 90% inactivated over 5 s at 0 mV (time consant of inactivation, tau h,
      approximately 2 s, 20-22 degrees C). Type I current, which activates at close to 
      60 mV, inactivated at about half this rate at the same potential, assuming that
      inactivation also proceeds to completion. 4. Type I whole-cell currents were
      reversibly blocked by superfused beta-bungarotoxin (beta-BuTX; apparent KD = 46
      nM). beta-BuTX did not appear to reduce type II whole-cell currents at
      concentrations up to 500 nM. 5. In outside-out patches, the type I channel had an
      almost linear I-E relation over the potential range -60 to +60 mV with a quasi
      physiological [K+] gradient. A best linear fit gave a single-channel conductance
      of 12 pS under these conditions. In symmetrical 170 mM K+, type I channels had a
      single-channel conductance of 30 pS over the same potential range. 6. More slowly
      activating type II single-channel currents were also recorded in inside-out
      patches. With symmetrical 170 mM K+, the major conductance level was close to 9.0
      pS. With a quasi-physiological [K+] gradient, type II single channels exhibit
      outward rectification that is reasonably well described by the Goldman-Hodgkin
      Katz current equation. 7. In the presence of 2 nM externally superfused alpha
      dendrotoxin (alpha-DTX), or 50 nM superfused beta-BuTX, unitary currents were
      recorded (outside-out patches, -60 or -50 mV) that were smaller than control type
      I currents. Virtually all transitions in the presence of 50 nM beta-BuTX were at
      one-third of the control current level. The currents did not conform to the
      characteristics of type II. 8. The electrophysiological and pharmacological
      characteristics of the type I channel strongly suggest that it is a member of the
      mammalian K+ channel subfamily of Shaker homologues, most similar to the
      homomultimeric Kv1.1 translation product. The type II channel may be a member of
      the mammalian Shab subfamily. 9. Possible roles for Na+ channels and type I K+
      channels in the Schwann cell are discussed.

PMID- 8745281
TI  - Activation by intracellular ATP of a potassium channel in neurones from rat
      basomedial hypothalamus.
AB  - 1. Cell-attached recordings from isolated glucose-sensitive hypothalamic neurones
      show that on removal of extracellular glucose there is an increased action
      current frequency concomitant with decreased single-channel activity. Conversely
      activation of single K+ channels was observed when extracellular glucose was
      increased. Isolation of membrane patches into the inside-out configuration
      following cell-attached recording demonstrated the presence of an ATP-activated
      K+ channel. 2. The ATP-activated K+ channel was characterized by a mean single
      channel conductance of 132 pS in symmetrical 140 mM KCl solutions. Single-channel
      open-state probability (Po) was not calcium dependent, and the presence of
      calcium did not prevent activation of the channel by ATP. 3. Activation of the
      channel by ATP was concentration dependent and the Po of the ATP-activated
      channel was unaffected by membrane voltage, regardless of the degree of
      activation elicited by ATP. 4. Open and closed time histograms were constructed
      from inside-out and cell-attached recordings and were consistent with a single
      open and two closed states. Channel openings were grouped in bursts. Application
      of ATP, in isolated patches, and glucose, in cell-attached patches, increased the
      burst duration and number of bursts per second and decreased the slow closed
      state time constant. In neither case was there a significant change in the fast
      closed-state time constant nor the open-state time constant. 5. The non
      hydrolysable ATP analogue adenylylimidodiphosphate (AMP(PNP)) and 'Mg2(+)-free'
      ATP produced little change in the Po of the ATP-activated K+ channel when applied
      to the intracellular surface of excised patches. These results suggest that
      activation of this channel is via an enzymic mechanism. 6. ADP, GTP and GDP also
      activated the channel in a Mg(2+)-dependent manner. ADP and ATP activated the
      channel in an additive manner and neither GTP nor GDP inhibited channel activity
      induced by ATP. 7. It is concluded that the ATP-activated K+ channel observed in
      isolated inside-out patches from hypothalamic neurones is the same as the channel
      activated by an increase in the concentration of extracellular glucose in cell
      attached recordings from glucose-sensitive neurones.

PMID- 8745282
TI  - Modulation of the hyperpolarization-activated Cl- current in human intestinal T84
      epithelial cells by phosphorylation.
AB  - 1. Hyperpolarization-activated Cl- currents (ICl,hyp) were investigated in the
      T84 human adenocarcinoma cell line, using the patch-clamp whole-cell
      configuration. 2. During whole-cell recording with high-chloride and ATP
      containing internal solutions, hyperpolarizing jumps from a holding potential of
      0 mV elicited slow inward current relaxations, carried by Cl- and detected at
      membrane potentials more negative than -40 mV. Analysis of the relative
      permeabilities to monovalent anions gave the following sequence: Cl- > Br- > I- >
      glutamate. 3. ICl,hyp was partially inhibited by 1 mM diphenylamine-2-carboxylic
      acid or 0.1 mM 5-nitro-2-(3-phenylpropylamino)-benzoate, and was completely
      blocked by Cd2+ (> 300 microM). It was insensitive to 1 mM external 4,4'
      diisothiocyanatostilbene-2,2'-disulphonic acid or 1 mM Ba2+. 4. ICl,hyp was
      inhibited by external application of 500 microM cptcAMP (8-(4-chlorophenylthio)
      adenosine 3':5'-cyclic monophosphate) or 500 nM of the protein kinase C
      activator, phorbol 12-myristate, 13-acetate. 5. (i) Omission of ATP from the
      pipette solution, (ii) ATP replacement by the non-hydrolysable ATP analogue 5'
      adenylylimidodiphosphate, and (iii) inhibition of protein kinase C by
      staurosporine or calphostin C accelerated the activation kinetics of the current
      and increased its amplitude, but did not alter its pharmacological properties. 6.
      We conclude that hyperpolarization-activated Cl- channels similar to those of ClC
      2 channels (mammalian homologue of Torpedo chloride channel ClC-0) are present in
      T84 cells, and that their gating properties are modulated by phosphorylation.

PMID- 8745283
TI  - Electrophysiological and morphological properties of interneurones in the rat
      dorsal lateral geniculate nucleus in vitro.
AB  - 1. Intracellular recordings were made from putative interneurones (n = 24) and
      thalamocortical (TC) projection neurones (n = 45) in slice preparations of the
      rat dorsal lateral geniculate nucleus (dLGN) in order to compare the
      electrophysiological properties of these neuronal types. 2. Intracellular
      injection of biocytin to electrophysiologically identified neurones (n = 34)
      revealed the morphology of putative interneurones (n = 4) to be similar to class
      B and that of TC neurones (n = 30) to be similar to class A Golgi-impregnated
      neurones. 3. Interneurones had resting membrane potentials (-52 mV) relatively
      positive to those of TC neurones (-63 mV), shorter time constants (36.8 and 58.2
      ms, respectively), but similar steady-state input resistances (164 and 180 M
      omega, respectively). Steady-state voltage-current relationships were nearly
      linear in interneurones, but highly non-linear in TC neurones. 4. The structure
      of action potential firing evoked at the break of hyperpolarizing voltage
      transients was dependent upon neuronal type. Interneurones fired a single action
      potential or a burst of action potentials with a maximum frequency of < 130 Hz,
      whilst TC neurones fired a high frequency burst with a minimum frequency of > 250
      Hz. In addition, well-defined burst firing of action potentials in response to
      depolarizing voltage excursions, from membrane potentials negative to -65 mV,
      could be evoked in TC neurones, but not in interneurones. 5. The directly evoked
      action potentials of interneurones were characterized by an initial slow pre
      potential preceding the fast upstroke of the action potential. The amplitude and
      width of interneurones' action potentials were smaller than those of TC neurones
      and the amplitude and duration of the single action potential after
      hyperpolarization were greater in interneurones. Both interneurones and TC
      neurones fired action potentials repetitively in response to suprathreshold
      voltage excursions, with interneurones demonstrating a greater degree of spike
      frequency adaptation. Following a train of action potentials, interneurones and
      TC neurones generated a slow after-hyperpolarizing potential: in interneurones
      but not TC neurones this potential was followed by a slow depolarizing potential.
      6. An intrinsic, subthreshold membrane potential oscillatory activity with a mean
      frequency of approximately 8 Hz was observed in interneurones. 7. Electrical
      stimulation of the optic tract evoked in interneurones apparently pure EPSPs,
      pure IPSPs or a mixture of EPSPs and IPSPs. EPSPs were found to be biphasic and
      mediated by the activation of non-N-methyl-D-aspartate (NMDA) and NMDA excitatory
      amino acid receptors. IPSPs and the response to the iontophoretic application of
      GABA were found to reverse between -65 and -70 mV. The application of GABAB
      receptor agonists failed to affect the membrane properties of six of seven
      interneurones tested. In addition spontaneous EPSPs and IPSPs were recorded in
      interneurones. 8. These results demonstrate that the electrophysiological
      properties of putative interneurones are distinct from those of TC neurones of
      the rat dLGN. The implications of these findings for the control of visual
      responsiveness of TC neurones are discussed.

PMID- 8745284
TI  - Amplitude and time course of evoked and spontaneous synaptic currents in rat
      submandibular ganglion cells.
AB  - 1. Excitatory postsynaptic currents (EPSCs) were recorded in rat submandibular
      ganglion cells in vitro using the two-electrode voltage clamp technique. 2. The
      peak amplitude of EPSCs evoked by nerve impulses in single presynaptic fibres
      varied between 1.2 and 9.8 nA in different cells (mean = 4.6 +/- 2.6 nA; n = 23; 
      80 mV membrane potential; 22-25 degrees C). 3. Experiments were performed to re
      investigate a previous hypothesis that different mechanisms underlie the
      generation of evoked versus spontaneous quantal EPSCs in submandibular cells.
      This hypothesis was based on the observation of different time courses of evoked
      and spontaneous EPSCs. 4. In agreement with previous studies, the time course of
      the decay phase of evoked EPSCs was described by the sum of two exponentials,
      with time constants tau 1 and tau 2 of 6.9 +/- 0.7 and 34.4 +/- 7.7 ms,
      respectively (n = 23; -80 mV membrane potential). 5. The double-exponential decay
      of evoked EPSCs persisted when transmitter release was reduced by bath addition
      of 100 microM cadmium chloride to the level of failures, one or several quanta.
      6. Spontaneous EPSCs exhibited mean amplitudes of 81 +/- 24 pA (n = 5 cells; -80
      mV membrane potential), and displayed an extremely wide range of peak amplitudes
      in the same cell (mean coefficient of variation (c.v.) = 0.37 +/- 0.09; n = 5
      cells). In contrast to a previous report (see below), the decay phase of
      spontaneous EPSCs was found to exhibit a double-exponential time course with time
      constants similar to those of the evoked EPSC recorded in the same cell. 7. These
      results indicate that evoked and spontaneously released quanta of transmitter
      most probably act on the same population of postsynaptic receptors in
      submandibular ganglion cells. There is a large variability in the peak amplitudes
      of quantal EPSCs recorded in the same cell. This large variability is not due to
      electrotonic effects, since these cells lack dendrites.

PMID- 8745285
TI  - Spindle oscillation in cats: the role of corticothalamic feedback in a
      thalamically generated rhythm.
AB  - 1. Spindles represent an oscillatory activity (7-14 Hz) of the
      electroencephalogram (EEG) originating in the thalamus and appearing during early
      stages of sleep. We investigated: (i) the phase relations between thalamic and
      cortical neurons during this rhythm; (ii) the patterns of spindles under
      different anaesthetics and their modifications at various levels of the membrane
      potential (Vm); and (iii) the potentiating role of the corticothalamic feedback
      in the genesis of spindles. Intra- and extracellular recordings were performed in
      cats from reticular and dorsal thalamic nuclei, as well as from various cortical
      areas. 2. In thalamic reticular neurons, spindles were sequences of waves at 7-14
      Hz, riding on a prolonged depolarizing plateau and occurring in phase with depth
      negative cortical EEG waves. In thalamocortical cells, spindles consisted of
      inhibitory postsynaptic potentials (IPSPs) in phase with depth-positive cortical
      EEG waves and occasionally leading to rebound spike bursts. In cortical cells,
      spindle waves were rhythmic (7-14 Hz) excitatory postsynaptic potentials (EPSPs)
      that sometimes gave rise to action potentials. Spindles occurred in phase among
      thalamic reticular, thalamocortical and neocortical neurons. 3. In thalamic
      reticular neurons, spindle waves and their depolarizing plateaux increased in
      amplitude with slight cellular hyperpolarization, but at a Vm more negative than 
      80 or -85 mV they decreased in amplitude. No frequency alterations were observed
      with these Vm changes. 4. The waxing-and-waning pattern of spontaneous spindles
      under barbiturate anaesthesia was distinct from the waning pattern under ketamine
      xylazine anaesthesia. Under all anaesthetics, spindles had a waning pattern when
      elicited by cortical stimuli. The amplitude of cortical-evoked spindle waves
      diminished with the decrease in stimulation intensity. 5. Under urethane or
      ketamine-xylazine anaesthesia, spindle sequences were grouped by a cortically
      generated slow oscillation (< 1 Hz) and were preceded by a depth-positive EEG
      wave that corresponded to a prolonged hyperpolarization in all three investigated
      (cortical, thalamic reticular, and thalamocortical) cellular types. 6. We propose
      that the waxing pattern of spindle oscillation is due to a progressive
      entrainment of units into the oscillation until a maximum number is reached,
      depending on the background activity in the network. The phase relations between
      cortical, thalamic reticular and thalamocortical neurons are ascribed to
      distributed excitatory signals from thalamocortical neurons to both cortical and
      reticular neurons at each cycle of the oscillation. In turn, cortical neurons
      provide a powerful drive to potentiate the genesis of thalamic spindles.

PMID- 8745286
TI  - Effect of chronic vitamin E deficiency on sympathetic and sensorimotor function
      in rat mesenteric arteries.
AB  - 1. Mesenteric arterial beds from male rats deprived of vitamin E for 12 months
      postweaning were isolated and perfused at 5 ml min-1. 2. The basal perfusion
      pressure of vitamin E-deficient preparations was significantly higher (34.0 +/-
      1.9 mmHg, n = 15) than in age-matched controls (26.1 +/- 2 mmHg, n = 14; P <
      0.01). 3. At basal tone, vasoconstrictor responses to electrical field
      stimulation (EFS) were not attenuated by vitamin E deficiency; at high
      stimulation frequencies, responses were enhanced. According to dose-response
      curves, exogenous noradrenaline was significantly more efficacious in
      preparations from vitamin E-deficient rats (P < 0.05). 4. In preparations with
      tone raised by methoxamine (6-20 microM) and in the presence of guanethidine (5
      microM), EFS of perivascular sensorimotor nerves elicited frequency-dependent
      vasodilatation which was significantly attenuated by vitamin E deficiency. There
      was no difference in relaxation to calcitonin gene-related peptide (CGRP; 1.5 x
      10(-11) mol), or to the sensory neurotoxin capsaicin (5 x 10(-11) mol). 5.
      Immunohistochemical analysis of CGRP-containing nerves in the superior mesenteric
      artery showed no differences in density of innervation. 6. In conclusion, chronic
      vitamin E deficiency impairs sensorimotor vasodilatation in rat mesenteric
      arteries; this does not appear to be due to changes in postjunctional receptors,
      or to a depletion of transmitter (CGRP) content of the superior mesenteric
      artery. Sensorimotor nerves appear to be more vulnerable than sympathetic nerves
      to chronic vitamin E deficiency.

PMID- 8745287
TI  - Strain of passive elements during force enhancement by stretch in frog muscle
      fibres.
AB  - 1. The force enhancement during and after stretch (0.15 micron per sarcomere) was
      studied during fused tetani of single fibres isolated from the anterior tibialis
      muscle of Rana temporaria (0.5-3.6 degrees C; sarcomere length, 2.05-2.65
      microns). Changes in length were recorded simultaneously from the fibre as a
      whole (puller movement) and from marked segments (approximately 0.5 mm in length)
      of the same fibre. 2. The residual force enhancement after stretch (recorded at
      the end of a long tetanus) was found to be linearly related to the slow component
      of tension rise during the stretch ramp. 3. The fibres were released to shorten
      against a very small load at different times after stretch (load clamp). The
      shortening records derived after a preceding stretch exhibited a larger and
      steeper initial transient than that recorded in an isometric tetanus without
      stretch. The excess length change (LS; nanometres per half-sarcomere) recorded
      during the initial transient increased with the amplitude of stretch and was
      linearly related to the force enhancement produced by the stretch (FE; % of
      maximum tetanic tension) according to the following regression: LS = 0.200 FE +
      8.65 (P < 0.001). The length changes recorded from the whole fibre agreed well
      with measurements from individual segments. 4. Slack-test measurements confirmed
      the existence of a large initial transient phase when the fibre was released to
      shorten after a preceding stretch. The excess length change determined from the
      slack tests agreed closely with the values derived from load-clamp recordings. 5.
      The results support the view that stretching a muscle fibre during tetanus leads
      to strain of elastic elements and, presumably, to variation of filament overlap
      due to non-uniform distribution of the length change within the fibre volume.
      Regions with greater filament overlap are likely to generate the long-lasting
      extra force referred to as 'residual force enhancement after stretch'. The
      elastic elements recruited during stretch can be presumed to play an essential
      part in this process by supporting regions in which the filament overlap has been
      reduced during the stretch ramp. Recoil of these elastic elements is responsible
      for the excess length change that is recorded during the initial transient after
      release as described under point 3.

PMID- 8745288
TI  - Effects of diaphragm shortening on the mean action potential conduction velocity
      in canines.
AB  - 1. The present study was designed to test if the mean muscle fibre action
      potential conduction velocity (VAPC) in the costal diaphragm changes with muscle
      length, in spontaneously breathing mongrel dogs. 2. VAPC was determined by the
      electromyogram (EMG) power spectrum 'dip' method, which is based on the bipolar
      electrode transfer function. A bipolar EMG electrode with a 20 mm fixed
      interelectrode distance was sutured to the costal diaphragm in the fibre
      direction, and in a region with a low density of motor endplates. Diaphragm
      length was measured with piezoelectric crystals positioned next to the EMG
      electrode. Seven dogs were vagotomized and spinally anaesthetized in order to
      increase diaphragmatic shortening, reduce velocity of shortening and abolish
      possible cross-talk signals from adjacent muscles. 3. Our results showed that
      VAPC in the canine costal diaphragm was 3.4 m s-1 and was not significantly
      related to diaphragmatic shortening.

PMID- 8745289
TI  - Contribution of shrinkage of extracellular space to extracellular K+ accumulation
      in myocardial ischaemia of the rabbit.
AB  - 1. The contribution of the concentrating effect due to shrinkage of the
      extracellular space (ECS) to cellular K+ efflux on extracellular potassium
      ([K+]o) accumulation in response to ischaemia was investigated in an isolated,
      blood-perfused rabbit papillary muscle preparation with a confined extracellular
      space. 2. The ECS was quantified using either of two extracellular markers,
      choline or tetramethyl ammonium (TMA), each with specific ion-selective
      electrodes, as well as by measurement of extracellular resistance (ro). [K+]o and
      [Na+]o were also measured simultaneously using K(+)- and Na(+)-selective
      electrodes. 3. During ischaemia, [K+]o increased 3-fold from 4.2 +/- 0.1 to 12.6
      +/- 1.0 mM at 10 min (n = 10) analogous to changes in the ischaemic heart in
      vivo. The ECS decreased to 83.9 +/- 3.2% of control measured using 1 mM choline
      extracellularly (n = 9, P < 0.01) or to 85.7 +/- 0.7% of control using 1 mM TMA
      (n = 6, P < 0.01). Nearly identical decreases in ro (84.1 +/- 2.4%, n = 15, P <
      0.01) occurred simultaneously. 4. The small decrease in the ECS contributed only
      0.8-0.9 mM to the total increase in [K+]o of 8.4 mM and had a minor effect on
      transmembrane K+ flux. No significant differences between the relative changes in
      [choline] and [Na+]o were observed. This excluded a major transmembrane Na+
      movement during early ischaemia. 5. Bumetanide (10 mM), an inhibitor of K(+)-Cl-
      cotransport, a process which is involved in cell volume regulation consequent to
      osmotic cell swelling, significantly attenuated the increase in [K+]o after 6 min
      of ischaemia (8.3 +/- 0.6 mM, n = 5 vs. 10.3 +/- 0.4 mM in the control group, n =
      6, P < 0.05), whereas N-ethylmaleimide (1 mM), a stimulator of this
      cotransporter, augmented [K+]o accumulation (12.0 +/- 0.6 mM at 6 min, P < 0.05).
      6. We conclude that during early myocardial ischaemia, a major component of [K+]o
      accumulation is not caused by diminution of ECS per se, but rather by increased
      net K+ efflux due in part to K(+)-Cl cotransport secondary to myocyte volume
      regulation.

PMID- 8745290
TI  - Regulation of L-arginine transport and nitric oxide release in superfused porcine
      aortic endothelial cells.
AB  - 1. We have investigated whether changes in extracellular ion composition and
      substrate deprivation modulate basal and/or bradykinin-stimulated L-arginine
      transport and release of nitric oxide (NO) and prostacyclin (PGI2) in porcine
      aortic endothelial cells cultured and superfused on microcarriers. 2. Saturable L
      arginine transport (Km = 0.14 +/- 0.03 mM; Vmax = 2.08 +/- 0.54 nmol min-1 (5 x
      10(6) cells)-1) was pH insensitive and unaffected following removal of
      extracellular Na+ or Ca2+. 3. Cationic arginine analogues, including L-lysine and
      L-ornithine, inhibited L-arginine transport, whilst 2-methylaminoisobutyric acid,
      beta-2-amino-bicyclo[2,2.1]-heptane-2-carboxylic acid, L-phenylalanine, 6-diazo-5
      oxo-norleucine, L-glutamine, L-cysteine and L-glutamate were poor inhibitors. 4.
      Deprivation of L-arginine (30 min to 24 h) reduced intracellular free L-arginine
      levels from 0.87 +/- 0.07 to 0.40 +/- 0.05 mM (P < 0.05) and resulted in a 40%
      stimulation of L-arginine, L-lysine and L-ornithine transport. 5. L-arginine and
      NG-monomethyl-L-arginine (L-NMMA), but not N omega-nitro-L-arginine methyl ester
      (L-NAME), trans-stimulated efflux of L-[3H]arginine. 6. Depolarization of
      endothelial cells with 70 mM K+ reduced L-arginine influx and prevented the
      stimulation of transport by 100 nM bradykinin, but agonist-induced release of NO
      and PGI2 was still detectable. 7. Basal rates of L-arginine transport and NO
      release were unaffected during superfusion of cells with a nominally Ca(2+)-free
      solution. Bradykinin-stimulated L-arginine transport was insensitive to removal
      of Ca2+, whereas agonist-induced NO release was abolished. 8. Although bradykinin
      stimulated NO release does not appear to be coupled directly to the transient
      increase in L-arginine transport, elevated rates of L-arginine influx via system
      y+ in response to agonist-induced membrane hyperpolarization or substrate
      deprivation provide a mechanism for enhanced L-arginine supply to sustain NO
      generation.

PMID- 8745291
TI  - The role of nitric oxide in the regulation of macromolecular transport in rat
      jejunum.
AB  - 1. Nitric oxide is known to affect epithelial and microvascular permeability and
      is a major non-adrenergic non-cholinergic neurotransmitter in the intestine. We
      have previously demonstrated neuronal regulation of macromolecular transport in
      the intestine. To define this regulation further the role of nitric oxide was
      investigated. 2. Stripped rat jejunum was mounted in Ussing chambers exposing the
      mucosal surface to bovine serum albumin (BSA; 2 mg ml-1), or BSA (2 mg ml-1) plus
      [125I]BSA (10 microCi). Following a 50 min equilibration, serosal fluids were
      sampled for four 10 min periods, and fluxes determined for intact BSA by enzyme
      linked immunosorbent assay (ELISA) and total BSA by [125I]BSA under basal
      conditions, and after treatment with NG-nitro-L-arginine-methyl ester (L-NAME)
      alone or in conjunction with L-arginine or decarboxylated molsidomine (SIN 1). 3.
      L-NAME significantly increased intact BSA uptake. Total (intact + degraded) BSA
      flux was not altered. The L-NAME effect was reversed by L-arginine and SIN 1.
      Additional experiments were performed by adding the nitric oxide donors sodium
      nitroprusside and SIN 1 directly to control tissue. Nitric oxide donors did not
      further decrease intact BSA flux below levels obtained from control tissue. The L
      NAME enantiomer D-NAME had no effect. Sodium-free bathing solutions also had no
      effect on intact BSA uptake. Non-specific permeability, as assessed by the
      serosal to mucosal movement of [51Cr]ethylene-diamine-tetraacetate ([51Cr]EDTA),
      was decreased with L-NAME. 4. The findings indicate that nitric oxide
      downregulates intact macromolecular flux in the small intestine.

PMID- 8745292
TI  - Expression and regulation of a vesicular monoamine transporter in rat stomach: a
      putative histamine transporter.
AB  - 1. Vesicular monoamine transporters (VMATs) translocate monoamines from the
      cytoplasm into secretory vesicles of endocrine cells and neurones, but they have
      limited affinity for histamine, and the identity of the vesicular transporter for
      this monoamine is uncertain. The aims of the present study were to characterize
      VMAT representatives in rat gastric corpus, and to determine if their expression
      was regulated by factors that modulate histamine biosynthesis. 2. Polymerase
      chain reaction (PCR) cloning using oligonucleotide primers to DNA sequences
      conserved within the VMAT family provided evidence for VMAT2, but not VMAT1 in
      rat gastric corpus. Northern analysis using a VMAT2 complementary RNA probe
      revealed a single 4 kb mRNA species in corpus endocrine cells. 3. In rats treated
      for up to 5 days with the H(+)-K(+)-ATPase inhibitor omeprazole, VMAT2, histidine
      decarboxylase and chromogranin A mRNA abundance in gastric corpus, and plasma
      gastrin concentrations increased progressively. Omeprazole also elevated VMAT2
      expression in rats fasted for 48 h, but fasting alone, or refeeding fasted
      animals had no effect. 4. The results are consistent with a role for VMAT2 in the
      transport of histamine into enterochromaffin-like cell secretory vesicles, and
      with upregulation of the transporter to accommodate the increased histamine
      biosynthesis and secretion that accompanies achlorhydria.

PMID- 8745293
TI  - Transferable circulating factors and epithelial sodium transport after unilateral
      nephrectomy in the rat.
AB  - 1. In order to investigate the role of circulating serum factors in the altered
      renal haemodynamics and enhanced renal tubular transport observed in renal
      growth, micropuncture experiments were performed on normal animals infused with
      20% plasma derived from animals in whom unilateral nephrectomy had been performed
      3 days previously. 2. When animals infused with plasma from uninephrectomized
      animals (NxP) were compared with those infused with control plasma, the former
      had a higher tubular fluid flow rate measured at both the late proximal (LP; 26.7
      +/- 1.6 vs. 18.4 +/- 1.4 nl min-1; P < 0.001) and early distal (ED; 14.9 +/- 1.0
      vs. 7.8 +/- 1.0 nl min-1; P < 0.0001) sites, which was reflected in the final
      urine flow rate (16.1 +/- 3.4 vs. 5.1 +/- 0.8 microliter min-1; P < 0.005). 3.
      The single nephron glomerular filtration rate (SNGFR) was higher in animals
      infused with NxP as determined from samples taken at the LP (45.8 +/- 2.8 vs.
      35.7 +/- 2.3 nl min-1; P < 0.01) and at the ED (34.5 +/- 2.5 vs. 28.1 +/- 1.8 nl
      min-1; P = 0.05) sites. However, this increase was not reflected in the whole
      kidney GFR (1.04 +/- 0.06 vs. 0.89 +/- 0.06; P = 0.07), suggestive of a
      preferential increase in filtration in the outer cortical nephrons. 4. Tubular
      Na+ transport was higher in the animals infused with NxP as evidenced by a
      decrease in the fractional delivery of Na+ at the ED site (4.5 +/- 0.4 vs. 6.5 +/
      0.6% of the filtered load; P < 0.05). However, in the final urine there was a
      significant increase in the urinary sodium excretion in animals infused with NxP
      (0.67 +/- 0.14 vs. 0.29 +/- 0.09%; P < 0.05) indicating that natriuresis and
      probably diuresis was a result of inhibition of Na+ and water transport in the
      late distal tubule and collecting duct. 5. In conclusion, these experiments
      demonstrate that circulating factors induced by a reduction in renal mass
      significantly alter glomerular filtration and tubular Na+ transport.

PMID- 8745294
TI  - Mechanism of action of ATP on canine pulmonary vagal C fibre nerve terminals.
AB  - 1. The effects of extracellular adenosine 5'-triphosphate (ATP) on pulmonary
      vagal afferent fibres (n = 46) was studied in a canine model in vivo (n = 38). 2.
      ATP (3-6 mumol kg-1), administered as a rapid bolus into the right atrium,
      elicited a transient burst of action potentials in cervical vagal fibres, which
      was not affected by either blockade of ganglionic transmission (hexamethonium) or
      a drop in arterial blood pressure (nitroglycerine). 3. The fibres with ATP
      sensitive terminals were otherwise quiescent with no activity related to either
      cardiac or respiratory cycles and their conduction velocity was 0.85 +/- 0.13 m s
      1 (n = 7). 4. Inflation of the lungs to 2-3 times the tidal volume triggered
      brief bursts of action potentials in these fibres. 5. Capsaicin (10 micrograms kg
      1), given as a rapid bolus into the right atrium, elicited a burst of action
      potentials in these ATP-sensitive fibres. 6. Smaller amounts of ATP and capsaicin
      (0.5-3 mumol kg-1 and 1-5 micrograms kg-1, respectively) had similar effects when
      the two compounds were given into the right pulmonary artery. 7. Adenosine,
      adenosine 5'-monophosphate, or adenosine 5'-diphosphate did not excite these
      fibres (n = 30). 8. The non-degradable analogue of ATP alpha,beta-methylene ATP
      (alpha,beta-mATP) was tenfold more potent than ATP while beta,gamma-methylene ATP
      (beta,gamma-mATP) was in active. 9. The selective P2x-purinoceptor antagonist
      pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid markedly attenuated the
      effect of ATP but not of capsaicin. The P2Y-purinoceptor antagonist Reactive Blue
      2 was without effect. 10. Pretreatment with pertussis toxin (PTX) did not affect
      this action of ATP. 11. In the canine lungs ATP activates vagal C fibre nerve
      terminals. This action is mediated by P2X-purinoceptors and is independent of a
      PTX-sensitive guanine nucleotide binding protein (G protein).

PMID- 8745295
TI  - Characterizations and comparisons of eupnoea and gasping in neonatal rats.
AB  - 1. Our purpose was to characterize the ventilatory patterns of eupnoea and
      gasping in the neonatal rat. This study was precipitated by reports, using in
      vitro brainstem spinal cord preparations, that only a single pattern is present
      in neonatal rats. 2. In anaesthetized or decerebrate rat pups aged less than 13
      days, eupnoea was characterized by a sudden onset of inspiratory activity and
      then a more gradual rise to peak levels. Following vagotomy, frequency fell and
      peak phrenic activity and tidal volume increased. The rate of rise of inspiratory
      activity also rose, but peak levels were still achieved during the latter half of
      inspiration. Vagal efferent activity exhibited bursts during both inspiration and
      the early expiration. This basic eupnoeic rhythm was not altered after sectioning
      of the carotid sinus nerves. 3. Upon exposure to hypoxia or anoxia, phrenic
      activity, tidal volume and frequency initially increased and then declined. In
      many animals, ventilatory activity then ceased, but later returned with a gasping
      pattern. 4. Gasping was characterized by a sudden onset of phrenic activity,
      which reached a peak intensity during the early portion of inspiration. The
      expiratory burst of vagal activity was eliminated. 5. Reductions of body
      temperature from 37 to 27 degrees C resulted in prolongations of inspiration and
      expiration and decreases of phrenic amplitude; phasic phrenic activity completely
      disappeared in some animals. Upon exposure to anoxia, gasping was observed, even
      in animals in which phrenic activity had disappeared in hyperoxia. 6. We conclude
      that, from the day of birth, rats can exhibit eupnoea and gasping patterns which
      are very similar to those of adult animals. 7. The rhythmic neural activities of
      the in vitro brainstem-spinal cord preparation, reported by others, differ
      markedly from eupnoea but are identical with gasping. We therefore conclude that
      this preparation is not suitable for investigation of the mechanisms that
      generate eupnoeic breathing.

PMID- 8745296
TI  - Physiological and molecular aspects of human implantation.
AB  - A greatly increased amount of knowledge on the preimplantation embryo and the
      molecular biology of the uterus have led to the development of new concepts on
      the adhesion of the embryo to the uterus and on the implantation process. This
      brief review covers cleavage and blastocyst formation, and the preparations of
      the embryo for implantation. The molecular factors involved in human implantation
      are then described, including the role of the steroid hormones, cytokines,
      adhesion molecules and substrates. The changes occurring in the embryo and uterus
      during implantation are described. Brief descriptions of extravillous trophoblast
      and the role of immune-type responses in the uterus are given. Finally, the
      molecular aspects of human implantation are considered.

PMID- 8745297
TI  - Decidua in human implantation.

PMID- 8745298
TI  - Role of embryonic factors in human implantation.
AB  - Implantation biology is now at a stage where experimental science will be very
      productive in answering basic questions about the ability of an embryo to
      implant. The advancement of our knowledge of cytokines and growth factors has
      been critically important in fuelling the recent new understanding of embryo
      implantation. Specifically, our increased knowledge of the interleukin (IL)-1
      system, as well as leukaemia-inhibiting factor (LIF), epidermal growth factor and
      colony-stimulating factor-1, and the availability of recombinant protein,
      specific antibodies and knockout mice, have led to a more detailed outline of
      implantation events. LIF and IL-1 are the two systems where recent advances have
      suggested their importance in implantation events. Recently, LIF has been shown
      in mice to be an endometrial requirement for implantation and embryo development.
      Although LIF is a pleiotropic molecule, with many interactions in multiple body
      tissues, in the uterus, concentrations are elevated on day 4 of pregnancy.
      Experiments with knockout mice have shown the requirement for endometrial LIF for
      successful implantation. The IL-1 system, consisting of two agonists (IL-1 alpha
      and IL-1 beta), two receptors (IL-1R types I and II) and the homologous IL-1
      receptor antagonist (ra), has also been studied. Knowledge that the embryo
      secretes IL-1 suggested the interaction between embryonic IL-1 and endometrial
      receptor, which has been shown to occur. IL-1R type I is plentiful on endometrial
      epithelial cells and appears to interact with embryonically secreted IL-1 beta to
      favour implantation. Such implantation events in vivo in mice are blocked by the
      introduction of large quantities of IL-1ra, consistent with the hypothesis that
      appropriate interactions between agonist and receptor at the level of the
      endometrial surface are a requisite for successful implantation. As more specific
      information on each cytokine or growth factor system comes to light, more
      complete information on the multiple molecular steps of implantation will become
      apparent. However, it is clear that no single cytokine or growth factor will be
      able to explain the complicated events of embryo implantation. Such an important
      necessary phenomenon has multiple redundancies. The interactions between
      cytokines and growth factors are becoming increasingly apparent and will need
      more experimental evidence before a full understanding of implantation is
      available.

PMID- 8745299
TI  - The role of prostaglandins in blastocyst implantation.
AB  - This review summarizes the information available on the involvement of
      prostaglandins in blastocyst implantation, and examines their interactions with
      three other inflammatory mediators, platelet-activating factor (PAF), interleukin
      (IL-1) and corticotrophin-releasing factor (CRF). Essential elements of this
      information, consistent with the assumption that prostaglandins play an important
      role in implantation, appear to be: (i) the burst of endometrial prostaglandin
      production, following the blastocyst signal(s) or an artificial stimulus; (ii)
      the main localization of this production at the luminal epithelium and release
      towards the stroma; and (iii) the presence at the stromal level of specific
      progesterone-dependent binding sites for prostaglandin E2. In addition,
      accumulated data indicate a paracrine interaction at the endometrial level
      between PAF and prostaglandin E2, which could serve, among others, to amplify the
      embryonic signal(s). Pro-inflammatory cytokines IL-1 alpha and IL-1 beta may also
      play a significant role in endometrial response via the modulation of
      prostaglandin E2 production. Prostaglandins and IL-1 induce the expression of
      CRF, which acts as an autocrine/paracrine inflammatory regulator. CRF exhibits a
      strong vasoactivity in skin tests, inducing a local increase of capillary
      permeability at a concentrations of 10(-10) M. Levels of CRF and its mRNA were
      found to be higher in rat implantation sites compared with those in the
      interimplantation regions. Stromal cells were found to be positive for
      immunoreactive CRF at the implantation sites only. It is suggested that CRF may
      be involved in the local increase of capillary permeability seen in implantation
      sites, and that its production by stromal cells may be the consequence of a
      paracrine action of epithelial prostaglandin, released under the effect of PAF
      and IL-1, derived from or produced by blastocysts in endometrial cells.

PMID- 8745300
TI  - Interleukin-1 system crosstalk between embryo and endometrium in implantation.
AB  - Nowadays, cytokines and growth factors have become increasingly implicated in
      embryo implantation. Endometrial function, embryo secretions and embryo
      endometrial interactions require a continuous dialogue and synchronism between
      both partners (endometrium and embryo), not only at the endocrine level but also
      at the local (paracrine/autocrine) level. This review focuses on the interleukin
      1 system as an example of a local regulator in embryo implantation. Evidence
      demonstrating its presence and relevance to human endometrial physiology and
      human embryo development is presented. Finally, we show data which suggest the
      possible role of this cytokine in implantation.

PMID- 8745301
TI  - Immuno-endocrine interactions in early pregnancy.
AB  - First we recall briefly the status of inflammatory cytokines in the early
      implantation period. We then describe the status of leukaemia inhibiting factor
      (LIF) production in an in-vitro, relatively short-term, human decidual explant
      culture system. We show that in most infertile women with recurrent implantation
      failure following successful in-vitro fertilization, LIF production is
      statistically much lower than normal. Other parameters of LIF production in vitro
      are summarized briefly, and the effects of RU486 are shown. The TH2 status of
      normal pregnancy is described, together with the production of TH2 cytokines by
      decidua and placenta. These cytokines are deficient in the CBAXDBA/2 model of
      murine spontaneous early pregnancy loss. The defect can be corrected by
      alloimmunization, and more importantly by the injection of tau interferon. The
      significance of these data for early pregnancy signalling is discussed.

PMID- 8745302
TI  - Clinical approaches to increasing uterine receptivity during human implantation.
AB  - An improvement in clinical pregnancy rate follows a natural or induced period of
      amenorrhoea. The cause is unknown, but it could be related to the period of
      uterine 'rest' which may restore full function to the steroid-sensitive systems,
      such as the pinopodes, after a prolonged period of constant menstrual cycling.
      This may result in the restoration of uterine capacity for embryo implantation to
      levels typical of younger women. Some other avenues of research on the unusual
      aspects of human implantation are worth further study. An impaired uterine blood
      flow could lower the chances of implantation. Immunological factors may emerge as
      major elements in the human implantation process, because the neutralization of
      antiphospholipid antibodies may enhance the activity of early trophoblast.

PMID- 8745303
TI  - Endometrial responses to corpus luteum products in cycles with induced ovulation:
      theoretical and practical considerations.
AB  - Products of the corpus luteum have targeted actions on the endometrium. Besides
      steroid hormones, the corpus luteum produces biologically active substances which
      may be either unique or shared by the endometrium and other tissues. Here we
      review selected markers of the corpus luteum and the endometrium as candidates
      for functional markers of the interplay between the two sites and relative to
      various treatment modalities. In clinical routine, the assessment of luteal phase
      is performed by morphological criteria. The timing of endometrial biopsy is
      important because specimens taken at different stages of the luteal phase give
      different results. After human menopausal gonadotrophin (HMG) superovulation,
      there is dyssynchrony in the morphological maturation of endometrial glands and
      stroma, and a marked difference has been found in endometrial development between
      progesterone-supplemented and non-supplemented cycles. The expression of steroid
      hormone receptors in endometrium is affected by ovarian stimulation regimens.
      After gonadotrophin-releasing hormone analogue/HMG superovulation, the
      progesterone receptor (PR) has been found less frequently in progesterone
      supplemented cycles than in non-supplemented cycles. The relative distributions
      of oestrogen receptor and PR between epithelium and stroma have been reported to
      vary according to the number of days of progesterone exposure. Thus, the
      detection of PR in endometrial glands in the late luteal phase indicates that
      exposure of the endometrium to the action of progesterone is short. Certain
      biochemical changes in the uterus are not reflected in endometrial morphology.
      Under the influence of progesterone, secretory glandular epithelium synthesizes
      placental protein 14, more recently named glycodelin. Glycodelin inhibits the
      innate immune system and also has contraceptive actions. Endometrial glands
      secrete glycodelin into glandular lumen, uterine fluid and blood, where the
      concentrations rise during the last week of the secretory phase. The effects of
      various ovarian stimulation protocols on serum glycodelin concentrations are
      reviewed, along with recent studies on relaxin, prolactin and insulin-like growth
      factor binding protein 1, all products of the secretory endometrium.

PMID- 8745304
TI  - Effects of aging on the female reproductive system.
AB  - There is an evident decline in human fertility with age. The fundamental
      physiological question is whether the ovary, the uterus, or both are affected by
      the changes induced within the body by senescence. Based on clinical studies
      performed in in-vitro fertilization (IVF) laboratories, there is no doubt that
      age affects the oocyte. However, the effect of age on the remaining cellular
      components of the preovulatory follicle have yet not been fully elucidated. In
      addition, whether the ability of the uterus to have normal implantation of human
      embryos is age-related is also a matter of controversy. In this review, we
      analyse the results of our studies that were conducted in order to answer these
      relevant questions. In the first series of experiments we tested the hypothesis
      that the function of granulosa cells is affected in older patients (> or = 40
      years). In these experiments, we cultured in vitro granulosa-luteal cells from 15
      women aged < 40 years and 18 patients aged > or = 40 years undergoing IVF.
      Immunoreactive alpha-inhibin and progesterone were measured after 48 and 96 h in
      culture. The measurements showed a significantly higher secretion of inhibin (P <
      0.01) after 48 h, and progesterone (P < 0.05) after 48 and 96 h, in the younger
      as compared to the older group. In addition, we tested the ability of the uterus
      to sustain normal implantation by an analysis of our oocyte donation programme.
      In the first approach, we divided all the transfer cycles according to the age of
      the recipient. We found no differences among groups with regard to pregnancy,
      implantation or abortion rates. We explored this fundamental question further by
      performing oocyte donation cycles in which oocytes from the same donor were
      distributed into a recipient aged < 40 years and another recipient of > or = 40
      years. An analysis of 45 cycles in each group of recipients showed a significant
      (P < 0.05) increase in abortion rates in older as compared to younger patients.
      When the serum oestradiol concentrations were followed in those women who carried
      normal single ongoing pregnancies, we found that a significant increase in blood
      oestradiol concentrations (which probably represents the luteo-placental shift)
      was detected 2 weeks earlier in younger than in older patients, suggesting a
      defective vasculature of the uterus that could ultimately be the cause of an
      increased abortion rate in patients aged > or = 40 years. In conclusion, we
      firmly believe that senescence affects both the ovary (oocyte and granulosa
      cells) and the uterus, and these observations should be taken into account in
      order to advise our patients.

PMID- 8745305
TI  - Donor-recipient synchronization and the use of gonadotrophin-releasing hormone
      agonists to avoid the premature luteinizing hormone surge in oocyte donation.
AB  - Since the introduction of the oocyte donation technique in humans, a number of
      reports have been published reflecting the success and improvement of this
      technique. Initially, the most important problems were donor-recipient
      synchronization at the moment of donation and the premature secretory changes in
      the endometrium consequent to the spontaneous luteinizing hormone (LH) rise in
      patients that still showed ovarian function. Today, with the new substitutive
      hormonal protocols, these two major problems have been solved. The endogenous LH
      rise can be avoided by administering gonadotrophin-releasing hormone agonists,
      without any deleterious effects on implantation when they are used in patients
      with ovarian function. Donor-recipient synchronization is possible because the
      recipients can remain indefinitely with substitutive therapy until the donation
      becomes feasible. Here, our experiences with both new strategies are presented.

PMID- 8745306
TI  - Exploring the mechanism(s) of endometriosis-related infertility: an analysis of
      embryo development and implantation in assisted reproduction.
AB  - Several retrospective analyses of our in-vitro fertilization (IVF) and oocyte
      donation programmes have been carried out in an attempt to gain clinical
      knowledge of the factors implied in the aetiology of endometriosis-associated
      infertility. In a first approach, a comparison was made of the IVF outcome
      between 96 cycles in 78 patients with tubal infertility and 96 more cycles in 59
      women with endometriosis. The results indicate that endometriosis patients had a
      poor IVF outcome in terms of a reduced pregnancy rate per cycle (P < 0.0004), a
      reduced pregnancy rate per transfer (P < 0.002) and a reduced implantation rate
      per embryo replaced (P < 0.003). In a second study, we addressed the analysis of
      patients undergoing oocyte donation. The results showed that patients with this
      disease have the same chances of implantation and embryo development in vivo as
      other recipients when the oocytes come from donors without known endometriosis.
      However, when the results of oocyte donation were classified according to the
      nature of the oocytes donated, patients who received embryos derived from
      endometriotic ovaries showed a significantly (P < 0.05) reduced ability to
      implant compared with the remaining groups. In a third approach, we evaluated
      embryo development in vitro when women with and without endometriosis underwent
      IVF and embryo replacement 72 h after oocyte retrieval. We observed a
      significantly (P < 0.04) reduced number of blastomeres in embryos from
      endometriosis patients compared with controls, as well as an increased (P < 0.05)
      incidence of arrested embryos in vitro. Taken together, these observations
      suggest that infertility in endometriosis patients may be related to alterations
      within the oocyte which, in turn, result in embryos of lower quality, as
      demonstrated in our IVF programme, and a lower ability to implant, as shown in
      the oocyte donation model.

PMID- 8745307
TI  - Optimization of implantation in the in-vitro fertilization laboratory.
AB  - Implantation failure rates after in-vitro fertilization (IVF) can be reduced in
      the IVF laboratory using two different techniques: assisted hatching and embryo
      co-culture on monolayer feeder cells. A review of the different methodologies and
      the results gained using these techniques is reported. Preliminary results
      obtained in the Reproductive Medicine Service of the Institut Universitari
      Dexeus, Barcelona, Spain using these techniques are also presented.

PMID- 8745308
TI  - Materno-fetal immunobiology in normal pregnancy and its possible failure in
      recurrent spontaneous abortion?
AB  - Many features contributing to the success of pregnancy in humans have been
      identified over the last 20 years. Trophoblast cells (which form the interface of
      fetal tissue with the mother) have specialized immunological features which may
      confer unique transplantation protection for the fetus throughout pregnancy. Both
      syncytiotrophoblast and cytotrophoblast cells do not express classical class I
      [human leucocyte antigen (HLA)-A or -B] or II (HLA-DP, -DQ or -DR) major
      histocompatibility complex (MHC) alloantigens, and the regulation of these cell
      surface glycoproteins appears to be at the transcriptional level. In contrast,
      extravillous cytotrophoblast cells express the non-classical class I MHC molecule
      HLA-G. One form of HLA-G (HLA-G1) is potentially capable of presenting a variety
      of peptide antigens to T cells. Alternatively, HLA-G may act as a cell surface
      class I MHC molecule, protecting cytotrophoblast from maternal MHC non-restricted
      natural killer (NK) cell attack; the expression of HLA-G by otherwise HLA-null
      cell transfectants has been shown to decrease their sensitivity to NK cell
      mediated cytolysis. All fetal trophoblast populations throughout gestation
      express high levels of cell surface complement regulatory proteins, providing
      protection from complement-mediated damage at the materno-fetal interface.
      Analyses of trials with allogeneic leucocytes for the treatment of recurrent
      spontaneous abortion show little evidence of an improved success rate in
      immunized patients.

PMID- 8745309
TI  - T-helper 1-type immunity to trophoblast: evidence for a new immunological
      mechanism for recurrent abortion in women.

PMID- 8745310
TI  - Fibrinolytic system and reproductive process with special reference to
      fibrinolytic failure in pre-eclampsia.
AB  - Here we summarize the recent progress in research on the role of the fibrinolytic
      system in reproduction, with a special emphasis on the role of the plasminogen
      activator inhibitors in fetal development. Trophoblasts produce fibrinolytic
      proteins that can promote normal implantation and regulate blood flow to the
      fetus and placenta throughout pregnancy. Normal pregnancy is associated with a
      hypofibrinolytic state that is fundamentally caused by an increase in plasminogen
      activator inhibitors types 1 and 2. In pre-eclampsia, a fibrinolytic failure,
      resulting from an increase in plasma and placental concentrations of plasminogen
      activator inhibitor-1, was observed. The localized elevated concentrations of
      placenta plasminogen activator inhibitor-1 protein and mRNA observed in pre
      eclamptic patients would be expected to foster the deposition of fibrin and thus
      play a role in the complications associated with this disease. The decreased
      plasminogen activator inhibitor-2 concentrations in placenta and plasma from
      intrauterine fetal growth retardation pregnancies and the positive correlation
      between plasma/placenta plasminogen activator inhibitor-2 concentration and
      birthweight suggest that this inhibitor could be considered an adequate marker of
      placental function.

PMID- 8745311
TI  - Targeting the zona pellucida for immunocontraception: a minireview.
AB  - This minireview summarizes the main data relevant to the development of
      contraceptive vaccines based on zona pellucida (ZP) antigens, as well as the pros
      and the cons of this immunocontraceptive strategy. Even though the antifertility
      efficacy of anti-ZP antibodies in humans is not corroborated by a clear
      relationship between spontaneous autoimmunization against the ZP and infertility,
      passive and active immunization studies in laboratory animals have provided
      convincing results. The contraceptive action of anti-ZP antibodies, targeting
      events situated upstream of gamete fusion, is devoid of potential ethical
      concerns related to the destruction of early embryos. The high protein content of
      the mammalian ZP, knowledge of the complete amino acid sequence of the major ZP
      proteins, and the high degree of sequence homology between individual species all
      favour the rapid advancement of anti-ZP vaccine projects. However, certain
      sequences of ZP proteins, when incorporated into the vaccine construct, activate
      CD4+ T cells of the recipient organism to direct a cellular immune attack
      (autoimmune oophoritis) to other functionally relevant ovarian components
      (primordial follicles, steroidogenic cells). The search for the optimal
      combination of B cell and T cell epitopes in the vaccine construct will hopefully
      overcome this problem.

PMID- 8745312
TI  - Hormonal anti-implantation agents: antiprogestins.
AB  - Oestrogens and progestogens separately or in combination are able to prevent
      implantation with high efficiency, thus acting as interceptive agents. Current
      interceptive medical regimens include high-dose oestrogens, the association of
      oestrogens with progestogens or progestogens alone. Compounds with
      antiprogesterone properties, such as RU 486 (mifepristone) or ZK 98734
      (lilopristone), also exhibit a strong interceptive action which, as shown in
      animal models, is proportional to the dose and the day(s) of administration.
      Recent clinical studies show that RU 486 can be used successfully for postcoital
      interception. The regimen applied for this purpose consists of the intake of a
      single dose of 600 mg RU 486 within 72 h of a single act of unprotected
      intercourse. This treatment was found to be highly effective and to have a more
      favourably side-effect profile in comparison with the oestrogen-progestogen
      interceptive regimen. However, because of the induced irregularities of the
      cycle, the mifepristone regimen, as with the other hormonal methods, should not
      be used on a regular basis. Currently, all interceptive hormonal regimens are
      emergency methods. Their occasional use to prevent unwanted pregnancies may
      reduce the number of therapeutic abortions. However, the frequency and extent of
      their side-effects do not allow for a repeated postcoital use after every act of
      unprotected intercourse. Obviously, the development of an effective and safe
      'morning after pill' requires further basic and clinical investigations.

PMID- 8745313
TI  - The GB hepatitis viruses.
AB  - The genomes of three new flavi-like viruses, GBV-A, GBV-B and GBV-C have been
      identified. Nucleic acid molecules corresponding to the genomes of GBV-A and GBV
      B were isolated from tamarins with hepatitis which had been infected with the GB
      agent. RNA sequences corresponding to GBV-C have been shown to be present in sera
      from humans with non-A-E hepatitis. Sequence comparisons show that these three
      viruses are more closely related to each other and to hepatitis C virus (HCV)
      than to any other known viruses. Together with HCV they appear to form a discrete
      cluster of related viruses within the larger genus of flaviviridae. The
      pathological significance of these viruses and their association with hepatitis
      is currently emerging.

PMID- 8745314
TI  - Identification of hepatitis C virus by immunoelectron microscopy.
AB  - Sequencing of the hepatitis C virus (HCV) has provided a better understanding of
      the natural history, immunology, and epidemiology of this virus. However, the
      morphology of HCV has not been definitively characterized. In this study, through
      a sequence of concentration processes, virus-like particles were isolated from
      human serum and liver tissue, visualized by transmission electron microscopy and
      identified as hepatitis C virion by immunoelectron microscopy. Spherical flavi
      like virus particles, approximately 70 nm in diameter, were observed in the
      fraction with 1.04-1.12 g ml-1 sucrose density and bound to immunogold particles
      with monoclonal antibodies (mAb) against hepatitis C. The nucleocapsid of the
      particles, which were 50 nm in diameter, appeared to be icosahedral in structure
      and surrounded by an envelope covered with surface projections. A 'tadpole' form
      of particles was also observed. The findings indicate that the low buoyant
      density in sucrose and the morphological features of the hepatitis C virion are
      consistent with the characteristics of flaviviruses and pestiviruses.

PMID- 8745315
TI  - Sequence analysis of the hepatitis C virus (HCV) core gene suggests the core
      protein as an appropriate target for HCV vaccine strategies.
AB  - Hepatitis C virus (HCV) is a major healthproblem with a prevalence of 1% in the
      United States population, and a significant percentage of infected patients
      progress to chronic liver disease and cirrhosis. Interferon therapy has
      demonstrated that the immune system can be modulated to alter the acute course of
      the disease, but long-term treatments remain elusive. Prevention of hepatitis C
      infection is therefore an important strategy to mitigate the impact of this
      disease. Initial attempts at vaccination have focused on recombinant envelope
      vaccines, which have shown an ability to protect against very low titre
      challenges of HCV in chimps. The need for vaccines capable of protecting against
      higher titre challenges has led to the search for alternative vaccine strategies.
      The most highly conserved structural protein in the HCV genome is the core
      protein, and vaccine strategies targeting the core protein have been proposed to
      increase vaccine efficacy. The variability of HCV core sequences and genotypes in
      the Ann Arbor patient population are not known, and the present study was
      undertaken to assess the theoretical feasibility of developing a HCV core vaccine
      by excluding promiscuous core (C) gene variability as a mechanism of vaccine
      failure. Results of nucleotide and deduced amino acid sequence analysis from 13
      of 14 patients studied reveal a 93% nucleotide and 96.4% amino acid core sequence
      homology in the C gene regions studied. Genotype analysis revealed four of 14 to
      be type 1a and nine of 14 to be type 1b with one infection not being sufficiently
      characterized to determine genotype. These results demonstrate a sufficiently
      high degree of conservation of HCV core sequences in our patient population to
      permit design of a vaccine directed against core protein.

PMID- 8745316
TI  - Interferon-alpha 2a for chronic hepatitis B with e antigen or antibody:comparable
      antiviral effects on wild-type virus and precore mutant.
AB  - Recombinant interferon-alpha 2a (IFN-alpha 2a) in a total dose of 702 MU was
      given to 31 patients: nine with wild-type hepatitis B virus (HBV) and hepatitis B
      e antigen (HBeAg) (A); four with HBeAg and a mixed infection with wild-type HB
      and precore mutants (B); 11 with antibody to HBeAg (HBeAb) and a mixed infection
      (C); and seven with HBeAb and precore mutants alone (D). HBV DNA was not cleared
      in any patient in groups A and B. By contrast, in patients with HBeAb, HBV DNA
      was ultimately lost in four patients in group C, as well as in 10 patients in
      group D. Thus, patients with HBeAb and infected with precore mutants alone (D)
      lost serum HBV DNA more often than those with HBeAg and wild-type HBV (A).
      Patients with low pretreatment levels of HBV DNA cleared virus more frequently,
      and the response of precore mutant to IFN was comparable with that of wild-type
      HBV in patients who had a mixed infection. Based on these results, precore
      mutants do respond to IFN, and therefore, IFN is indicated in patients with
      HBeAb, especially those with low serum HBV DNA levels.

PMID- 8745317
TI  - Hepatitis B virus precore mutants in HBeAg carriers with chronic hepatitis
      treated with interferon.
AB  - Precore mutants of hepatitis B virus (HBV) were looked for in 18 hepatitis B e
      antigen (HBeAg) carriers who were treated with recombinant interferon-alpha
      (rIFN) and the results were compared with those obtained in 12 untreated carriers
      who underwent spontaneous HBeAb seroconversion. Molecular analysis of the HBV
      precore region was carried out by polymerase chain reaction (PCR) amplification
      and direct sequencing. Precore mutants with a stop codon at codon 28 were
      detectable at baseline in 19/30 carriers. However, wild-type strains predominated
      in the baseline sera of both treated (n = 16) and untreated (n = 10) patients.
      Sera from the remaining four patients contained predominantly or exclusively
      mutant virions. Following IFN treatment, there was a shift from the wild-type
      pattern to the mutant pattern in all patients, with the precore pattern
      prevailing in long-term responders (six out of nine) compared with the non
      responders (none of nine). The wild-type pattern predominated among the non
      responders (eight vs three), suggesting that the long-term response to IFN was
      associated with take-over of precore mutants. There were no relationships between
      any pretreatment precore molecular pattern and disease severity or outcome of
      treatment. Precore mutants also took over in 10 of the 12 untreated patients
      (83%), who underwent spontaneous HBeAb seroconversion. Thus, a shift from wild
      type to precore mutant pattern occurs in most Italian patients undergoing IFN
      induced or spontaneous HBeAb seroconversion.

PMID- 8745318
TI  - A high prevalence of antibodies to hepatitis C virus among commercial plasma
      donors from Western India.
AB  - A very high prevalence of anti-hepatic C virus (anti-HCV) antibodies (63/73,
      86.3%) was noted among commercial plasma donors of an organization manufacturing
      blood products, studied in 1989. Retrospective serological analysis of these
      donors revealed continued high prevalence of anti-HCV, i.e. 35/40 (87.5%) in
      1988, 28/31 (90.3%) in 1987 and 86/94 (91.4%) in 1986. HCV RNA detection by
      polymerase chain reaction (PCR) demonstrated 15/33 (45.45%) plasma donors to be
      positive in 1989. Interestingly, 3/24 (12.5%) serum samples collected from
      employees of the organization were also anti-HCV positive. All three anti-HCV
      positive employees were directly associated with plasmapheresis. Of the three
      anti-HCV positive employees one had been anti-HCV positive since 1985, but the
      other two employees were negative during 1985-1987 and then became positive in
      1987 and remained positive in 1989. One of these two employees was also a plasma
      donor. Commercial blood donors from a local blood bank had anti-HCV prevalence of
      13% which was significantly lower (P < 0.001) when compared with plasma donors of
      the organization and significantly higher than volunteer blood donors (< 0.25%, P
      < 0.01).

PMID- 8745319
TI  - Genotypic variation, clinical and histological characteristics of chronic
      hepatitis C detected at blood donor screening.
AB  - Since blood donor screening for the hepatitis C virus (HCV) began in 1991 a large
      number of seropositive subjects have been detected and several reports have
      suggested a high prevelance of liver disease. The aim of this study was to
      evaluate the severity of liver disease in HCV-positive blood donors in terms of
      the clinical, biochemical and histological abnormalities and to investigate the
      relationships between these features and the mode of transmission, duration of
      infection and viral genotype. We evaluated 54 consecutive blood donors who were
      positive for HCV both on serological testing and polymerase chain reaction.
      Twenty-three (43%) had a history of intravenous drug abuse and 17 (31%) had
      received blood transfusions. In only two (4%) was no risk factor identified. The
      mean duration of infection in those with a clear history of HCV exposure was 12
      years. Eighty-three percent were HCV genotypes 1 or 3. All had abnormal liver
      biopsies with chronic hepatitis and several patients had periportal or portal
      portal fibrous septa, but there was none with architectural distortion or
      cirrhosis. There was no correlation between severity of liver disease and
      duration of HCV infection, mode of transmission or viral genotype. In the
      majority of HCV carriers detected at donor screening there is a chronic hepatitis
      with bridging necrosis in one third, but the degree of fibrosis is minimal and
      cirrhosis was not present in our patients. The long period of infection of many
      patients suggests that irreversible liver injury does not necessarily develop at
      an early stage despite persistent infection.

PMID- 8745320
TI  - Tissue engineering and autologous transplant formation: practical approaches with
      resorbable biomaterials and new cell culture techniques.
AB  - The engineering of living tissues in vivo requires new concepts in cell culture
      technology. In contrast to conventional cell cultures, the development of tissues
      depends on a three-dimensional arrangement of cells and the formation or
      synthesis of an appropriate extracellular matrix. Special emphasis is given to
      the major role of the extracellular matrix and cell differentiation in an
      artificial tissue. New technical approaches of in vitro tissue engineering are
      compared to the natural development of tissues in vivo. Current methods using
      resorbable biomaterials, tissue encapsulation and perfusion culture are
      discussed. Major consideration is given to scaffold structures of biomaterials
      that define a three-dimensional shape of a tissue or guide matrix formation. The
      different goals of tissue engineering such as in vitro models and transplant
      production are taken into account in the described techniques. Practical concepts
      comprising cell multiplication and differentiation in subsequent steps for future
      clinical applications are outlined.

PMID- 8745321
TI  - Long-term storage of tissues by cryopreservation: critical issues.
AB  - The technique of cryopreservation (maintenance of biological samples in a state
      of 'suspended animation' at cryogenic temperatures), its potential use in tissue
      engineering applications and current obstacles to the development of effective
      cryopreservation methods for tissues are reviewed. A didactic overview of the
      principles of cryobiology and the methodology of cryopreservation is given, with
      emphasis on the processes of injury to cells during freezing and thawing, and how
      these are related to the physicochemical and biophysical changes occurring during
      cryopreservation. Critical issues relevant to the application of cryopreservation
      methods to tissues are then addressed, including heat and mass transfer
      limitations in these bulk systems, intrinsic differences between isolated and
      cultured cells, and mechanisms of freezing injury unique to tissue systems.

PMID- 8745322
TI  - Transport characterization of membranes for immunoisolation.
AB  - This study relates to the diffusive transport characterization of hollow fibre
      membranes used in implantable bio-hybrid organs and other immunoisolatory
      devices. Techniques were developed to accurately determine the mass transfer
      coefficients for diffusing species in the 10(2)-10(5) MW range, validated and
      then used to study one membrane type known to effectively immunoisolate both
      allografts and xenografts in vivo. Low-molecular-weight diffusing markers
      included glucose, vitamin B12 and cytochrome C; higher-molecular-weight molecules
      were bovine serum albumin, immunoglobulin G, apoferritin and a range of
      fluorescein-tagged dextrans. Overall and fractional mass transfer coefficients
      through the hollow fibres were determined using a resistance-in-series model for
      transport. A flowing dialysis-type apparatus was used for the small-molecular
      weight diffusants, whereas a static diffusion chamber was used for large
      molecular-weight markers. For diffusion measurements of small-molecular-weight
      solutes, convective artefacts were minimized and the effect of boundary layers on
      both sides of the membrane were accounted for in the model. In measuring
      diffusion coefficients of large-molecular-weight species, boundary layer effects
      were shown to be negligible. Results showed that for small-molecular-weight
      species (< 13,000 MW) the diffusion coefficient in the membrane was reduced
      relative to diffusion in water by two to four times. The diffusion rate of large
      molecular-weight species was hindered by several thousand-fold over their rate of
      diffusion in water.

PMID- 8745323
TI  - Dopamine secretion by PC12 cells microencapsulated in a hydroxyethyl methacrylate
      -methyl methacrylate copolymer.
AB  - A rat pheochromocytoma cell line (PC12) was encapsulated in a water-insoluble
      hydroxyethyl methacrylate-methyl methacrylate copolymer by interfacial
      precipitation from a polyethylene glycol 200 solution into phosphate-buffered
      saline. The resulting capsules (660 +/- 44 microns in diameter; 84 +/- 27 microns
      wall thickness) contained viable PC12 cells in a spheroidal arrangement, much
      like tumour spheroids, the latter grown on surfaces unsuitable for cell
      attachment. In these spheroids, the viable cells formed a band approximately 100
      microns thick, surrounding an inner core of necrotic cells. A similar arrangement
      was seen 14, 28 and 42 days after encapsulation, with capsules maintained in an
      in vitro tissue culture environment; the annular ring was roughly constant in
      size, although the packing density appeared to increase over the 6 week
      observation period. During the first 4 weeks, when measurements were made the
      encapsulated cells converted a tetrazolium dye (MTT) into an insoluble formazan
      product, in a time-after-encapsulation-dependent manner. This indicated that PC12
      cells retained viability despite encapsulation and an ability to increase (at
      least in part) their metabolic capacity, presumably by a combination of
      proliferation and altered cellular activity. The encapsulated PC12 cells also
      secreted dopamine when incubated in a high potassium release medium but not in a
      low potassium, conventional tissue culture medium (RPMI 1640). Consistent with
      the MTT results, the amount of dopamine released was also dependent on the time
      after encapsulation, as well as the cell density at the time of encapsulation.

PMID- 8745324
TI  - Time course of membrane microarchitecture-driven neovascularization.
AB  - The host response to a microporous material that induces neovascularization at
      the material-tissue interface was studied in terms of the number and types of
      cells invading the membrane, the degree of vascularization at the material-tissue
      interface, and the characteristics of the surrounding connective tissue as a
      function of time following implantation. Millipore-MF mixed esters of cellulose
      membranes with a nominal pore diameter of 8.0 microns were implanted
      subcutaneously into male Sprague-Dawley rats and explanted at 3, 5, 7, 10, 21 and
      329 days post-implantation. Two samples from each of two devices at each
      implantation time were embedded in paraffin, sectioned to a thickness of 5
      microns, and stained with haematoxylin and eosin for light microscopic
      observation. The density of cells in the membrane increased up to 7 days
      following implantation, then remained roughly constant through 21 days and
      decreased at the 329 day time point. The vascularity of the material-tissue
      interface increased up to 10 days and remained at this level even at 329 days
      post-implantation. The connective tissue was disorganized, loose and avascular at
      3 days, resembled granulation tissue at 5 days, and underwent fibrous capsule
      formation and maturation starting at 7 days following implantation.

PMID- 8745325
TI  - In vivo biostability of a polymeric hollow fibre membrane for cell encapsulation.
AB  - The biostability of poly(acrylonitrile-co-vinyl chloride) (P(AN/VC)) hollow fibre
      membranes was assessed in the rat peritoneal cavity over a 12 month period. The
      mechanical and chemical stabilities of the hollow fibre membrane (HFM) were
      characterized by measuring its tensile strength and molecular weight (by gel
      permeation chromatography) pre-implantation and post-explantation. The stability
      of the HFM transport properties was determined by molecular weight cut-off (MWCO)
      and hydraulic permeability (HP). Explanted HFMs were treated with 4 M NaOH to
      remove adsorbed protein before measuring mechanical, chemical and transport
      properties. The HFM was stable in vivo for at least 12 months: (i) weight average
      molecular weight (Mw) at t = 0 was 143,000 g mol-1 (with a polydispersity index
      (PDI) of 2.3) and at t = 12 months it was 128,000 g mol-1 (with a PDI of 2.8);
      and (ii) tensile strength at t = 0, 52 +/- 2 mdyne, did not change significantly
      over time and was 46 +/- 7 mdyne at t = 15 months (P > 0.05 by a two-tailed
      Student's t-test); and (iii) no significant differences, with respect to standard
      deviation, were observed in the transport properties: HP was 7.4 +/- 1.5 ml min-1
      m-2 mmHg-1 at t = 0 and 7.5 +/- 1.5 ml min-1 m-2 mmHg-1 at t = 12 months, while
      MWCO (at 90% rejection) was initially 40,000 +/- 8000 g mol-1 and then 54,000 +/-
      10,000 g mol-1 at t = 12 months.

PMID- 8745326
TI  - Recent advances in tissue synthesis in vivo by use of collagen-glycosaminoglycan
      copolymers.
AB  - Biologically active analogues of the extracellular matrix (ECM) are synthesized
      by grafting glycosaminoglycan (GAG) chains onto type I collagen, and by
      controlling the physicochemical properties of the resulting graft copolymer.
      Collagen-GAG ECM analogues have previously been shown to induce regeneration of
      the dermis in humans and the guinea pig, and of the rat sciatic nerve. Current
      studies have emphasized elucidation of the molecular mechanism through which
      tissue-specific ECM analogues induce regeneration. The contribution of the GAGs
      to the biological activity of the skin regeneration template was confirmed by
      studying the contribution of several GAGs to the inhibition of wound contraction
      in guinea pigs. The interaction between cells and the porous structure of an ECM
      analogue was studied with emphasis on the deformation of pores which occurs
      during wound contraction. The synthesis of scar, as well as of partly regenerated
      tissue which has a morphology between that appropriate for scar and for normal
      dermis, was quantitatively assayed for the first time using a laser light
      scattering technique. An ECM analogue which has been shown to be capable of
      inducing regeneration of functional sciatic nerve in the rat over a gap larger
      than 10 mm was incorporated in the design of a biodegradable implant for
      peripheral nerve regeneration.

PMID- 8745327
TI  - Neural tissue engineering: from polymer to biohybrid organs.
AB  - This investigation reports on the immobilization of neuronal and glial cells
      (Schwann cells and astrocytes) within N-(2-hydroxypropyl) methacrylamide (HPMA)
      polymer hydrogels for the production of cell-based polymer hybrid devices. Cells
      were included within HPMA polymer networks by gel-entrapment, and these biogels
      were maintained in vitro for up to 6 days. Cell viability and differentiation
      were studied using immunocytochemical methods and image analysis techniques. The
      polymer structure and its relationships with cells were examined by scanning
      electron microscopy. A proportion of the cell population was viable, expressing
      its own antigenic profile throughout the period of gel incubation, as cells do in
      conventional culture conditions, and some cells exhibited behaviour such as
      spreading or process outgrowth and secretion of laminin. The result of the
      present study allows us to envisage tissue replacement in the central nervous
      system by means of such cell-based polymer constructs.

PMID- 8745328
TI  - Cultured skin as a 'smart material' for healing wounds: experience in venous
      ulcers.
AB  - The healing of chronic wounds is a difficult and varied problem. The engineering
      of a cultured skin tissue offers an adaptive therapy for chronic wounds. Our
      hypothesis has been that living tissue can act as a 'smart material' to heal
      wounds. We have examined the healing characteristics of a bilayered cultured skin
      equivalent (Graftskin) in a controlled study and present clinical data from
      interim analyses for 233 patients over 6 months of treatment. All venous ulcer
      patients will be followed for up to 1 year. We report on three basic scenarios of
      healing: (i) promotion of healing by secondary intention, (ii) persistent
      biological wound closure with stimulation of underlying healing, and (iii)
      healing by frank graft take of the cultured material with remodelling of the
      tissue over time. Our results indicate that the cultured skin equivalent is
      responsive to individual wound conditions and thus acts as a 'smart material' in
      the chronic wound.

PMID- 8745329
TI  - Manufacture and characterization of poly(alpha-hydroxy ester) thin films as
      temporary substrates for retinal pigment epithelium cells.
AB  - For many disorders of the retinal pigment epithelium (RPE) for which there are no
      effective treatments, transplantation of RPE cells may provide a viable means of
      restoring function. Using a solvent casting technique, we have manufactured thin
      films of poly(L-lactic acid) and poly(DL-lactic-co-glycolic acid) 75:25 and
      50:50. Non-porous, flexible films with controlled thickness as thin as 12 +/- 3
      microns and reproducible surface morphologies and flexural properties were
      produced. Fetal human RPE cells were found to attach to these substrates when
      cultured in vitro. The films made using this technique may provide a means of
      transplanting allogeneic RPE cells as a therapy for a number of ocular diseases
      related to RPE dysfunction.

PMID- 8745330
TI  - Biointeractive polymers and tissue engineered blood vessels.
AB  - The regulation of endothelial cell (EC) and smooth muscle cell (SMC)
      proliferation following vascular interventions is critical to clinical efficacy.
      Our laboratory has developed a method of impregnating biomaterials with
      suspensions containing bioactive proteins resulting in the capability of
      differentially modulating EC and SMC growth in vitro and in vivo following
      implantation. We have previously reported that 60 mu internodal distance ePTFE
      grafts impregnated with fibrin glue (FG) containing FGF-1 and heparin develop
      confluent endothelialization with transiently increased EC and SMC proliferation
      after 4 weeks in dogs. Thoraco-abdominal implants after 20 weeks were developed
      significantly thicker (139 mu) inner capsules in response to the FGF. To minimize
      SMC proliferation we studied the effects of FGF-1, heparin, and thrombin
      concentrations on SMC growth in vitro. FG caused a 182% increase (P < 0.001) in
      DNA synthesis. Heparin within FG diminished this effect in a dose-dependant
      manner, with complete inhibition of FG-induced growth at 500 U ml-1 (versus FG
      alone, P < 0.001). FGF-1 within FG without heparin had no effect, but together,
      FGF-1 caused a dose-dependant growth increase while increasing heparin
      concentrations initially increased and then decreased proliferation. FGF-1 and
      heparin in the medium of quiescent SMCs had similar effects. Only thrombin
      concentrations > 3.2 U ml-1 stimulated SMC growth and this stimulation was
      blocked by heparin. A synergism between FGF and heparin on EC proliferation was
      also found but without EC growth inhibition in response to higher concentrations
      of heparin. It is thus possible to modulate the relative proliferative activity
      of ECs versus SMCs by altering the FGF:heparin ratio. This same system may be
      useful with other proteins to induce other local affects by the applied protein
      or systemic affects following release of that protein.

PMID- 8745331
TI  - Leucocyte adhesion under flow conditions: principles important in tissue
      engineering.
AB  - An understanding of inflammatory responses is important in a wide variety of
      tissue engineering applications. This review describes the current understanding
      of a central aspect of inflammatory responses, the adhesion of leucocytes to
      blood vessel walls prior to their emigration into tissues. These highly specific
      adhesive interactions are mediated by three main families of receptors: the
      selectins, integrins, and members of the immunoglobulin superfamily. Under flow
      conditions, the various receptors make distinct contributions to a multistep
      process of adhesion in which leucocytes roll, adhere firmly, and eventually
      transmigrate. Two examples in which these principles are important in tissue
      engineering research, lymphocyte adherence in transplant rejection and monocyte
      adherence in atherosclerosis, are discussed in the last part of the paper.

PMID- 8745332
TI  - Magnetically orientated tissue-equivalent tubes: application to a
      circumferentially orientated media-equivalent.
AB  - Circumferential orientation of collagen fibrils in a media-equivalent (ME) is
      achieved in a simple and effective way using the orientating effects of a strong
      magnetic field during collagen fibrillogenesis when the ME is first created.
      Circumferential orientation of the entrapped smooth muscle cells (SMC) is
      achieved subsequently via cell contact guidance, the induced SMC orientation
      along orientated fibrils. After describing the methods used, several lines of
      evidence are provided showing that the magnetically orientated ME is
      circumferentially orientated, including collagen birefringence, circumferential
      SMC orientation, accelerated ME compaction and increased ME stiffness with
      reduced creep in the circumferential direction as compared to control MEs not
      exposed to a magnetic field during fibrillogenesis. The optimization of these
      methods is discussed in order to better mimic the circumferential orientation and
      mechanical properties of a natural medium. Other applications of magnetically
      orientated tissue-equivalents are indicated.

PMID- 8745333
TI  - Characterization of the formation of interfacially photopolymerized thin
      hydrogels in contact with arterial tissue.
AB  - The aim of this study was to examine the conditions under which an interfacial
      photopolymerization process results in hydrogel barriers. Visible light initiated
      interfacial photopolymerization of a polyoxyethylene glycol (PEG)-co-poly(alpha
      hydroxy acid) copolymer based on PEG 8000 macromonomer was performed on porcine
      aortic tissue, resulting in conformal hydrogel barriers. The process conditions
      were optimized in vitro for the formation of a 5-100 microns thick barrier.

PMID- 8745334
TI  - Toward development of an implantable tissue engineered liver.
AB  - Hepatocyte transplantation on implantable devices is a tissue engineering
      approach to improve the treatment of liver disease and the efficacy of ex vivo
      gene therapy. Diverse physiological functions and high metabolic activity of the
      liver represent significant challenges to engineering implantable devices that
      provide long-term hepatic support. Liver tissue engineering research has explored
      alternatives to direct hepatocyte injection that include hepatocyte attachment to
      microcarriers, encapsulation and transplantation on biodegradable polymer
      scaffolds. Successful function of hepatocytes transplanted on implantable devices
      in animal models has been documented by production of albumin and other liver
      specific markers, and clearance of bilirubin and urea metabolites. Strategies
      used to achieve these successes are reviewed, with particular emphasis on
      biodegradable polymer scaffolds, and two areas of investigation that may improve
      the function of implantable tissue engineered liver devices are highlighted.

PMID- 8745335
TI  - Culture matrix configuration and composition in the maintenance of hepatocyte
      polarity and function.
AB  - Several extracellular matrix (ECM) configurations involving type I collagen and
      Matrigel were examined for their ability to support differentiated function and
      polarity of cultured adult rat hepatocytes. Collagen sandwich- and Matrigel-based
      cultures yielded superior and comparable albumin secretion for at least 2 weeks.
      In collagen sandwich, hepatocytes were polygonal, and formed multicellular
      arrays. Collagen sandwich was also found to promote in vivo-like polarization of
      F-actin, cell adhesion molecules (E-cadherin), and lateral (Na+, K(+)-ATPase,
      glucose transporter) and apical (dipeptidyl peptidase, aminopeptidase) membrane
      polarity markers, but not the expression of the gap junction protein connexin 32
      and the epidermal growth factor (EGF) receptor. In contrast, hepatocytes cultured
      in or on Matrigel were more rounded and formed aggregates. Matrigel-based
      cultures also elicited detectable levels of connexin and EGF receptor and an
      altered distribution of F-actin, E-cadherin, and apical and lateral membrane
      proteins. Composite sandwich configurations containing collagen I and Matrigel
      restored markers lacking in the collagen sandwich, and showed a variable
      morphology and membrane polarity. Hepatocyte polarity could thus be manipulated
      by the overall ECM composition. Furthermore, in composite sandwich cultures,
      these manipulations can be effected largely independent of changes in hepatocyte
      morphology and albumin secretion.

PMID- 8745337
TI  - British Paediatric Association Surveillance Unit: ninth annual report.

PMID- 8745336
TI  - Engineering of a sugar-derivatized porous network for hepatocyte culture.
AB  - Many tissue engineering applications require a scaffold or template conducive to
      cell attachment and maintenance of functions. It may also be advantageous in some
      cases for these scaffolds to have a controlled porous architecture to facilitate
      cellular or tissue ingrowth. In this study, we have engineered a porous
      carbohydrate-derivatized substrate for hepatocyte culture. Polystyrene foams,
      with pore sizes up to 100 microns, fabricated by phase separation from a
      homogeneous naphthalene solution, were derivatized with lactose and heparin, both
      of which are known to promote rat hepatocyte attachment and maintenance of its
      differentiated functions. Rat hepatocytes cultured on these derivatized foams
      exhibited a rounded cellular morphology with many microvilli evident on the
      surface of the cells. The hepatocytes showed an increase in albumin secretion for
      the first 3 days of culture in a defined, serum-free medium, and dropped back to
      initial levels by the end of 7 days. The production of cytochrome P450-dependent
      hydroxytestosterone metabolites were also measured. Two testosterone metabolites
      were maintained and five others were present but decreased over a culture period
      of 1 week. These carbohydrate-derivatized porous substrates may be useful for
      large-scale culture of hepatocytes, toxicology screening and for use in a liver
      assist device.

PMID- 8745338
TI  - Effects of a new cholinolytic drug of tropanes and its optical isomers on central
      muscarinic and nicotinic receptors.
AB  - 2 alpha-(2',2'-disubstituted-2'-hydroxy-ethoxy)tropane (2 alpha-DHET
      cholinolytic, is a racemic tertiary amine with two chiral carbonic atoms. It has
      four optical isomers whose absolute configurations are 1R-2 alpha-2'S, 1R-2 alpha
      2'R 1S-2 alpha'R and 1S-2 alpha-2'S. These compounds showed both antimuscarinic
      and antinicotinic activity, blocking both muscarinic and nicotinic receptors.
      Central muscarinic receptors, rather than nicotinic receptors, have a
      stereoselective specificity to these compounds. The 2'R configurations are more
      suitable to the stereostructure of the binding site of muscarinic receptors than
      the 2'S configuration.

PMID- 8745339
TI  - Insulinotropic action of meglitinide analogues: modulation by an activator of ATP
      sensitive K+ channels and high extracellular K+ concentrations.
AB  - At normal extracellular K+ concentration (5 mM), the meglitinide analogues A
      4166, KAD-1229, repaglinide and S3075, all tested at a 10 mu M concentration,
      markedly enhanced insulin release evoked by 6 mM D-glucose in isolated rat
      pancreatic islets. They failed, however, to augment the much higher rate of
      insulin release evoked by D-glucose in islets exposed to a high K+ concentration
      (30 mM). Under the latter conditions, the potent diazoxide analogue BPDZ-44 (50
      mu M) did not exert any sizeable effect upon insulin release. Even at normal K+
      concentration, BPDZ-44 (50 mu M), which suppressed glucose-stimulated insulin
      release, only caused a partial inhibition of the insulinotropic action of A-4166
      and failed to affect significantly insulin secretion in the presence of KAD-1229,
      repaglinide or S3075. These findings argue against the view that meglitinide
      analogues could affect cytosolic Ca2+ activity independently of the closing of
      ATP-sensitive K+ channels. The present results also indicate that, with the
      possible exception of A-4166 which in the least potent secretagogue in this
      series, meglitinide analogues are able, like hypoglycemic sulphonylureas, to
      fully protect ATP-sensitive K+ channels against their activation by BPDZ-44.

PMID- 8745340
TI  - Nootropic drugs have different effects on kindling-induced learning deficits in
      rats.
AB  - Kindling represents an accepted model of human epileptogenesis. Furthermore, it
      has been demonstrated that kindled rats show a diminished learning performance in
      an active avoidance task. In our study we administered different nootropic drugs
      to kindled rats to test their effects on learning a two-way active avoidance task
      in the shuttle-box. Kindling was induced by repeated intraperitoneal injections
      of 45 mg kg-1 pentylenetetrazol (PTZ) once every 48 h. The substances vinpocetine
      (0.1 and 1.0 mg kg-1), methylglucamin orotate (225 and 450 mg kg-1), piracetam
      (100 mg kg-1), and meclofenoxate (100 mg kg-1) were administered during kindling
      development and after kindling completion prior to each session in the learning
      experiment. The nootropic drugs had little if any effect on severity of seizures.
      Concerning their effect on learning the substances each acted in a specific
      manner. Methylglucamin orotate enhanced the learning deficit induced by kindling.
      Meclofenoxate injected prior to the kindling stimulation was ineffective, whereas
      administration prior to the learning test improved the learning performance
      effectively. A complementary action was shown in experiments with vinpocetine.
      Only piracetam prevented the occurrence of kindling-induced learning deficits
      regardless the administration schedule.

PMID- 8745341
TI  - Catecholaminergic responses in vas deferens isolated from rats submitted to acute
      swimming stress.
AB  - The study was performed to examine the responses to catecholamines in vas
      deferens isolated from rats submitted to acute swimming-induced stress. It was
      demonstrated that acute stress induces a significant subsensitivity of rat vas
      deferens to norepinephrine. This subsensitivity was inhibited when the experiment
      was carried out in the presence of either cocaine (10-5 M) or timolol (10-5 M).
      On the other hand, the rat vas deferens sensitivity to methoxamine was
      significantly increased by acute swimming-induced stress. Thus, despite acute
      swimming stress inducing a reduction in response to norepinephrine, the alpha1
      adrenoceptor-mediated contractile response was increased. Additionally there were
      increases in neuronal uptake and beta2-adrenoceptor activity that opposes the
      alpha1-adrenoceptor activity. Integrated, these phenomena are responsible for the
      rat vas deferens subsensitivity to norepinephrine which may be involved in body
      homeostasis in stressogenic situations.

PMID- 8745342
TI  - Metabolic and hormone-related responses to caffeine in rats.
AB  - The time course of effects of caffeine on plasma glucose and non-esterified fatty
      acids (NEFA) were measured and related to various hormonal responses associated
      with substrate mobilization and utilization. Participation of the sympatho
      adrenal system (SAS) in the metabolic and hormonal actions of caffeine was also
      investigated by the use of ganglionic blockade. Following 50 mg kg-1 i.p.
      injections of caffeine in rats, plasma glucose increased 25% and NEFA 40%, and
      these actions were parallelled by an elevation of plasma insulin, ACTH and
      corticosterone, without changes in glucagon. It is suggested that the insulin
      response is related to the plasma glucose increase and possibly also to an action
      of cAMP. When caffeine was injected in rats previously treated with the
      ganglionic blocker, hexamethonium, none of the responses mentioned above were
      modified. These results show that the glucose and NEFA responses are independent
      of glucagon secretion and are due not only to SAS activation but also to other
      mechanisms such as the increased ACTH and corticosterone secretion. It is also
      suggested that the mobilization of substrates by caffeine is mediated, through
      these various mechanisms, by the activation of cAMP and by phosphodiesterase
      inhibition.

PMID- 8745343
TI  - Inhibitory effect of the somatostatin analogue SMS 201-995 and cytokines on the
      proliferation of human colon adenocarcinoma cell lines.
AB  - The activity of the synthetic somatostatin analogue SMS 201-995 was investigated
      in vitro on the growth of SW480 and SW620 human colon adenocarcinoma cell lines.
      The inhibition of cell proliferation was significant in SW480 cells (-19.6 +/-
      1.4% at SMS 201-995 10-9 M, P < 0.05), but not in SW620 cells (-5.5 +/- 0.8% at
      SMS 201-995 10-8 M) as compared to untreated cultures. Moreover, SMS 201-995 10-8
      M decreased the mitogenic effect of epidermal growth factor (EGF) on the SW480
      cell line (-26.6 +/- 3.4% vs. cells exposed to EGF 10 ng ml-1 alone, P < 0.05).
      The effect of combining SMS 201-995 plus the cytokines interleukin-2 (IL-2) or
      gamma-interferon (gamma-IFN) on SW480 and SW620 cancer cell growth was also
      evaluated. The treatment produced a synergistic antiproliferative effect against
      SW620 cells as compared to untreated cultures, with growth inhibition being -20.2
      +/- 1.2 and -19.3 +/- 1.3%, at SMS 201-995 10-8 M plus IL-2 or gamma-IFN 100 IU
      ml-1, respectively, but did not increase the activity of SMS 201-995 against the
      SW480 cells. In conclusion, the effect of SMS 201-995 on colon cancer cell growth
      can be enhanced by its combination with cytokines in SW620 but not in SW480 colon
      adenocarcinoma cells.

PMID- 8745344
TI  - A rifampicin-induced hepatic microsomal enzyme system for the generation of
      cyclosporine metabolites.
AB  - A drug-induced rabbit hepatic microsomal enzyme system has been developed to
      produce milligram quantities of cyclosporine metabolites (CMs). Using a
      rifampicin-induced microsomal preparation in the presence of a NADPH regenerating
      system, 60% of the cyclosporine (CsA) was converted to CMs in 2 h. The CMs were
      recovered by solid phase extraction, and separated by gradient high performance
      liquid chromatography with two Ultrasphere Ocyl (C8) columns connected in tandem.
      More than 20 CMs were resolved. The quantities of major CMs produced by 45 mg of
      microsomal proteins were established by comparing peak areas with known
      concentrations of authentic CM standards. These major CMs included AM1, AM9,
      AM19, AM4N, AM1c and the aldehydic isomers (AM1cAL plus AM1AL). Other CMs that
      were not quantified included AM14N, AM4N9, AM1A, AM1c9, and AM1D1. Several CMs
      remained to be identified. All CMs were detected by radioimmunoassay using a non
      specific CsA antiserum. The purity of the CMs were confirmed by fast atomic
      bombardment mass spectrometry. Similar findings were observed when erythromycin
      or trolandomycin was used to induce the hepatic microsomal enzymes. The procedure
      used to generate CMs was simple. With the enzyme fraction derived from one rabbit
      liver, 90 to 100 mg of CMs can be obtained. In this study, the metabolite
      patterns of CsA produced by rabbit liver microsomes were shown to resemble those
      observed for humans. These results indicate the possibility of using rabbit
      models to predict CsA biotransformation in man. The CMs generated by this enzyme
      system can be used to acquire information relevant to the situation in man.

PMID- 8745345
TI  - Regulation of glibenclamide receptors in cultured chick cardiomyocytes.
AB  - We found that the expression of sulphonylurea receptors which control ATP
      dependent potassium channels was up-regulated both by a receptor agonist and by
      potassium channel activators. Sulphonylurea receptors detected on cell membranes
      of cultured chick cardiomyocytes by [3H]glibenclamide were increased 2.8-fold
      following growth of the cells for 1-2 days in the presence of 30 nM
      glibenclamide. [3H]glibenclamide binding was also increased approximately 2-fold
      following growth of the cells in the presence of the ATP-dependent potassium
      channel activators, pinacidil, minoxidil and diazoxide, but was diminished to 75%
      of control following treatment with depolarizing concentrations of KCl.

PMID- 8745346
TI  - Effects of cromakalim, pinacidil and glibenclamide on cholinergic transmission in
      rat isolated atria.
AB  - The effect of the potassium channel openers cromakalim and pinacidil, and the
      potassium channel blocking drug glibenclamide, were investigated on cholinergic
      transmission in rat isolated atrial preparations which had been incubated with
      [3H]-choline to incorporate [3H]-acetylcholine into the cholinergic transmitter
      stores. The efflux of radioactivity evoked by electrical field stimulation of
      intrinsic parasympathetic nerves (pulses at 5 Hz frequency in trains of 60 s
      duration) was taken as an index of transmitter acetylcholine release. Stimulation
      induced (S-I) efflux of radioactivity was virtually abolished by tetrodotoxin (1
      mu M) and by the removal of Ca2+ from the atrial superfusion fluid. The
      muscarinic cholinoceptor antagonist atropine (0.3 mu M) and the alpha2
      adrenoceptor antagonist idazoxan (0.3 mu M) each enhanced the S-I efflux.
      Cromakalim (1 and 10 mu M) produced concentration-dependent reductions in S-I
      efflux. Pinacidil (10 mu M) also reduced S-I efflux. The inhibition of S-I efflux
      produced by cromakalim (10 mu M) and pinacidil (10 mu M) was prevented by the ATP
      sensitive potassium channel blocking drug glibenclamide (1 mu M). Moreover,
      glibenclamide (1 mu M) alone enhanced S-I efflux. The findings suggest that
      cromakalim and pinacidil may inhibit transmitter acetylcholine release from
      atrial parasympathetic nerves by activation of ATP-sensitive potassium channels.
      In addition, the finding that glibenclamide alone enhanced S-I efflux in
      radiolabelled atrial preparations suggests that ATP-sensitive potassium channels
      are activated under the experimental conditions employed. Taken together, the
      findings indicate that, in rat atria, ATP-sensitive potassium channels may play a
      functional role in the regulation of transmitter acetylcholine release from
      parasympathetic cholinergic nerve terminals.

PMID- 8745347
TI  - Effect of L-cysteine on lipid peroxidation in experimental urolithiatic rats.
AB  - Oxalate, the major stone-forming constituent induces lipid peroxidation during
      lithogenesis. In experimental condition oxalate formation was induced by the
      administration of its precursor glycollate. Glycollate-fed rats showed increased
      susceptibility to lipid peroxidation in the presence of promoters. In addition,
      antioxidant enzymes-catalase, superoxide dismutase and glutathione peroxidase
      also showed decreased activity. Reduced glutathione, total thiols and ascorbic
      acid were also significantly decreased. On the other hand, an increased xanthine
      oxidase and decreased glucose-6-phosphate dehydrogenase activity was also
      observed upon glycollate administration. Cysteine, a sulphydryl compound, is
      known to inhibit free radical toxicity in various pathologies. Cysteine
      administration to glycollate-fed rats brought about a significant decrease in the
      peroxidative level, with an increase in the antioxidant status.

PMID- 8745348
TI  - Docetaxel: a new defence in the management of breast cancer.
AB  - The results of nine phase II trials of docetaxel in the first- and second-line
      treatment of patients with advanced breast cancer are summarized. All 316
      patients included in this report received docetaxel at a dose of 100 mg/m2
      administered over 1 h every 3 weeks on an outpatient basis. One hundred and fifty
      four patients received docetaxel as first-line therapy for advanced disease, half
      of whom had received prior adjuvant chemotherapy (finished at least 1 year
      previously). An overall response rate of 59% (95% CI: 51-67) was achieved in
      these patients, with a median duration of response of 8.3 months and a median
      time to progression of 4.9 months. Similar results were seen in a subgroup of 68
      patients with liver metastases. Among the 162 patients given docetaxel as second
      line therapy, 134 had strictly defined anthracycline-resistant disease; 73 had
      liver metastases. The combined overall response rate for anthracycline-resistant
      patients in two US studies was 48% (95% CI: 37-59) while that in a multicenter
      French study was 29% (95% CI: 18-44). The median duration of response in each
      case was 6.3 and 5.5 months, respectively, with an overall median survival
      duration of 11 and 10 months, respectively. Among patients with liver metastases,
      second-line treatment with docetaxel achieved an overall response rate of 32%, a
      median duration of response of 7.8 months and a median survival duration of 9
      months. These results for docetaxel as both first- and second-line therapy are
      comparable with those achieved with doxorubicin and are particularly promising in
      patients with liver metastases and anthracycline-resistant disease.

PMID- 8745349
TI  - Docetaxel: meeting the challenge of non-small cell lung cancer management.
AB  - The combined results of four phase II studies of docetaxel in non-small-cell lung
      cancer (NSCLC) are presented. All patients had either locally advanced (stage
      IIIb) or metastatic (stage IV) disease. Results are given for the 248 patients
      included in the trials who received docetaxel at a dose of 100 mg/m2 given by
      intravenous infusion every 21 days on an outpatient basis. Among 200 patients
      evaluable for response, the overall response rate was 31.3% in 128 previously
      untreated patients and 19.4% in 72 previously treated patients. A subgroup of 30
      previously treated patients who were platinum-refractory achieved a response rate
      of 13.5%. In previously untreated and previously treated patients, median
      duration of response was 24.6 weeks and 28.7 weeks, respectively, with median
      times to progression of 14.4 weeks and 13.6 weeks and median survival durations
      of 9.0 months and 8.1 months. Similar response rates were achieved in patients
      with stage IIIb and stage IV disease (32% and 25%, respectively) and in patients
      with visceral metastases (28%) although patients with single-organ involvement
      did better than those with two or more organs involved. Response rates were
      comparable to or better than those seen with previous single-agent
      chemotherapeutic regimens for advanced NSCLC and even with some combination
      treatments, with a tolerable adverse event profile.

PMID- 8745350
TI  - Docetaxel: an interesting new drug for the treatment of head and neck cancers and
      soft tissue sarcomas.
AB  - Results are summarized for two phase II studies of docetaxel as first-line
      therapy for advanced squamous cell carcinoma of the head and neck (SCCHN) and one
      study of docetaxel as second-line therapy for advanced soft tissue sarcomas. In
      all three studies, docetaxel was administered at a dose of 100 mg/m2 by
      intravenous infusion over 1 h every 3 weeks. A total of 62 patients were enrolled
      in the SCCHN trials, of whom 57 were evaluable for response. The combined overall
      response rate in the SCCHN patients was 35%. Median duration of overall response
      was 6.5 months in the EORTC-ECTG study. In the DFCI study, median durations of
      complete and partial remission were 6.75 months and 4.45 months, respectively.
      These results are at least comparable to those achieved with other single-agent
      therapies in this setting. In the soft tissue sarcoma study, 29 of the 31
      patients enrolled were evaluable for response. Five patients (17%) achieved a
      partial response to docetaxel as second-line therapy and a further nine (31%) had
      stable disease. Median duration of response in these patients with soft tissue
      sarcomas was 5 months. Again, these results are similar to those seen with the
      three most active single agents in soft tissue sarcomas when used as second-line
      therapy. Docetaxel may therefore represent a useful drug in both advanced SCCHN
      and soft tissue sarcomas.

PMID- 8745352
TI  - Chaos in the case notes.

PMID- 8745351
TI  - Docetaxel delivers new management opportunities for gastrointestinal carcinomas.
AB  - The results of four phase II studies of docetaxel in cancers of the
      gastrointestinal tract are summarized. No prior chemotherapy was permitted except
      for adjuvant chemotherapy completed at least 1 year before entering the present
      study. In all studies, docetaxel was administered at a dose of 100 mg/m2 given by
      intravenous infusion over 1 h once every 3 weeks, adjusted according to toxicity.
      Routine premedication for hypersensitivity reactions was given to most patients
      in the US study in colorectal cancer but not to patients in the three European
      studies in gastric, pancreatic and colorectal cancers. In a European Organization
      for Research on Treatment of Cancer--Early Clinical Trials Group (EORTC-ECTG)
      study in gastric cancer, 8 (24%) of 33 evaluable patients achieved partial
      remissions lasting for a median of 7.5 months. Responses occurred in a variety of
      metastatic sites. Forty-two patients were evaluable in a French study of
      docetaxel in pancreatic cancer. Partial responses were achieved in 6 (20%) of 30
      patients with metastatic disease and 3 of 12 patients with loco-regional disease
      showed some improvement. Two studies in colorectal cancer--one European and one
      US--found that docetaxel had little or no activity in these patients. Three (9%)
      of 33 evaluable patients in the European study achieved responses (one complete
      and two partial) and none of 19 patients in the US study. Hematological toxicity
      was the dose-limiting adverse effect. Acute hypersensitivity reactions and fluid
      retention also occurred in some patients. In conclusion, docetaxel appears to be
      as effective as standard single-agent therapies for gastric and pancreatic
      cancers but to have minimal effect in colorectal carcinoma. Toxicities were
      generally manageable; premedication with corticosteroids may reduce the incidence
      and severity of acute hypersensitivity reactions and delay the onset of fluid
      retention.

PMID- 8745354
TI  - Inequitable variation.

PMID- 8745353
TI  - Human tissues: legal and ethical issues.

PMID- 8745355
TI  - Senescence, cancer and 'endogenous parasites': a salutogenic hypothesis.
AB  - The integrity and health of an organism can be considered as a state actively
      imposed by specialised 'salutogenic' mechanisms (immune, endocrine, paracrine
      etc) on an innate tendency towards internal conflict. One major source of
      internal conflict arises from the operation of natural selection upon replicating
      sub-organismal components such as cells, organelles and gene sequences. From this
      perspective cancer is seen not as a pathological process arising in a healthy
      organism but as caused by the capacity of replicating cells to evolve 'selfish'
      adaptations and elude the finite repertoire of integrative mechanisms. Cancer can
      therefore be regarded as one instance of a more general tendency towards
      senescence due to the failure of salutogenesis and accumulation of endogenous
      parasites. This may provide a new and potentially fruitful approach to framing,
      analysing and understanding the aetiology of the degenerative diseases of
      senescence.

PMID- 8745356
TI  - The King's College Hospital Acute Stroke Unit.
AB  - The King's College Hospital (KCH) Acute Stroke Unit (ASU) was set up in January
      1994 in order to provide acute management for patients admitted with stroke and
      to undertake biomedical research. Of 206 patients admitted to KCH with a stroke
      or suffering an in-hospital stroke, 141 (68%) patients were admitted to the ASU
      over its first 6 months of operation: 120 (85%) were from the Accident and
      Emergency Department and 21 (15%) from other wards. Management included
      resuscitation and medical stabilisation, investigation, prevention of stroke
      complications (including aspiration, venous thrombosis, and pressure sores),
      rehabilitation (physiotherapy, occupational therapy, speech and language
      therapy), nutrition (dietetics) and initiation of secondary prevention measures
      (aspirin or anticoagulation, blood pressure and lipid lowering, and carotid
      endarterectomy). All aspects of management are driven by agreed guidelines.
      Patients remain under the care of the admitting physician but specific stroke
      management and guidance is provided by two research doctors and the unit's
      nurses, therapists and dietician. The unit also facilitates research into stroke
      pathophysiology and acute therapeutic interventions. Our experience suggests that
      an ASU is relatively easy to set up and may contribute to improved care. Whether
      ASUs improve patient survival and functional outcome, and are cost-effective,
      requires further study.

PMID- 8745357
TI  - Anxiety, depression and management of medically unexplained symptoms in medical
      clinics.
AB  - This study assessed the prevalence of medically unexplained symptoms in
      cardiology, gastroenterology and neurology outpatient clinics at a large teaching
      hospital and investigated the current clinical management of these patients. Data
      were collected retrospectively from the casenotes of all new referrals to these
      clinics over a two month period. The total number of new patients seen was 343,
      of whom 120 (35%) had a final diagnosis of 'functional' disorder, 204 (59.5%) a
      final diagnosis of organic disorder and 19 (5.5%) remained undiagnosed. The
      number of investigations was similar in patients whether the eventual diagnosis
      was 'functional' or organic (median 2, range 0-9 in each case). However, the cost
      of investigation was significantly higher for the organic group (median 89 pounds
      compared with 41 pounds, p > or = 0.01). Anxiety and depression were documented
      in 33% of patients with unexplained symptoms. In 73 (61%) of patients with an
      eventual 'functional' diagnosis, the information that organic disease had been
      excluded was communicated to the GP, but there was no advice about further
      management. Four percent were referred to psychiatrists and 2% started on
      antidepressants. The paucity of recommended management strategies for patients
      with a 'functional' diagnosis suggests that physicians see their role with this
      group of patients as primarily one of exclusion of organic disease. It is
      suggested that more positive management strategies, including treatment of
      anxiety and depression, might lead to greater patient satisfaction and play a
      role in reducing the development of chronic somatisation.

PMID- 8745358
TI  - A neurological rehabilitation unit: audit of activity and outcome.
AB  - A clinical audit was carried out to determine the impact of multidisciplinary
      rehabilitation in a specialist neurorehabilitation unit, and to demonstrate how
      outcome measurement can be incorporated into routine clinical audit. The study
      describes and interprets the results of one year's activity and outcome in a
      neurorehabilitation unit. A total of 138 patients were admitted to the 18 bedded
      unit between April 1994 and March 1995. The main outcome measures were: length of
      inpatient stay, admission and discharge destination, disability as measured by
      the Barthel Index and Functional Independence Measure, handicap as measured by
      the Environmental Status Scale and the Handicap Assessment Scale, and the time
      spent undertaking the audit. Improvement in disability was demonstrated in 112
      (83%) patients and in handicap in 89 (66%) patients. The time taken to analyse
      the data on a quarterly basis was reduced from 20 hours for the first quarter to
      4.5 hours for the last quarter. The results show that multidisciplinary inpatient
      neurorehabilitation leads to functional improvement in the majority of
      neurologically impaired patients. Outcome measurement and data collection can be
      incorporated into routine clinical practice once a sound methodology has been
      established.

PMID- 8745359
TI  - Management of artificial nutrition in East Anglia: a community study.
AB  - In the Cambridge health district the growth of artificial nutritional support was
      prospectively assessed over a five-year period (1988-93). The aim of this study
      was to investigate the variation in the prevalence of enteral tube feeding (ETF)
      and parenteral nutrition (PN) in hospital and at home and to assess the
      organisation. There was a fourfold variability in the prevalence of artificial
      nutritional support in the eight districts. The prevalence of home artificial
      nutrition doubled between 1988 and 1993, whilst that in hospital increased to a
      smaller extent (31%). Overall standards of care are not keeping pace with the
      demand for artificial nutritional support. Only half the districts had nutrition
      teams, and only one had a specialist nutrition sister. Policies about ETF and PN
      in hospital and at home were judged to be variable in quality. About one in five
      patients (or carers) at home experienced problems related to organisation of
      nutrition support services. General practitioners were also frequently uncertain
      about their role in managing patients on artificial nutrition at home. Home ETF
      is a rapidly growing form of home care therapy in East Anglia; in 1992-93 it was
      quantitatively as important as ETF in hospital. Improvements in organisation are
      recommended.

PMID- 8745360
TI  - Audit of the investigation and outcome of iron-deficiency anaemia in one health
      district.
AB  - The investigation of iron-deficiency anaemia (IDA) is a clinical problem which
      arises in virtually all branches of medicine. To audit the investigation of IDA,
      a computer-based laboratory record system was used to identify all women over 50
      years of age and all men (n = 200) presenting to a single district laboratory
      with probable IDA in a six-month period. In 21 of 130 incident cases anaemia was
      clearly attributable to non-gastrointestinal disease. Of the remaining 109, 19%
      had investigation of both upper and lower gastrointestinal tract, 21% the upper
      gastrointestinal tract only, and 7% the lower gastrointestinal tract only. In 55
      cases either no investigation was performed or only faecal occult blood tests.
      Eighteen months after presentation nine colorectal cancers, five gastric cancers
      and 11 peptic ulcers had been diagnosed; 21 patients had died, including two from
      colorectal cancers not detected when the IDA presented. This audit has revealed
      substantial underinvestigation of probable IDA, with serious but treatable
      conditions remaining undetected. Our findings, which we have no reason to believe
      are unrepresentative, indicate that policies are needed to ensure adequate
      investigation of IDA.

PMID- 8745361
TI  - National audit of the quality of the clinical blood transfusion process. New
      audit measures for good practice in blood transfusion medicine.

PMID- 8745362
TI  - The role of preventive medicine in sickle cell disease. The Watson Smith lecture.
AB  - Homozygous sickle cell disease is one of the most common genetic abnormalities in
      the world; it affects approximately 100,000 births annually in Nigeria alone.
      With this scale of public health problem, the newer high technology approaches to
      prevention, such as antenatal diagnosis, or to treatment, such as bone marrow
      transplantation, are unlikely to be affordable or to have a discernible
      population impact. Experience in Jamaica suggests that many low technology
      affordable procedures can markedly reduce the morbidity and mortality of the
      disease. Furthermore, certain aspects of current management in the United
      Kingdom, such as frequent hospital admission and transfusion, not only consume
      scarce resources but may increase morbidity. Prophylactic penicillin to prevent
      pneumoccocal complications, education of parents so as to reduce the mortality
      from acute splenic sequestration, awareness of the features and epidemic pattern
      of aplastic crises, and exchange transfusion for the acute chest syndrome
      represent cost-effective measures which may markedly influence outcome. Reducing
      dependency on inpatient facilities might actually reduce morbidity and save
      resources that could be used to improve day care and outpatient management.

PMID- 8745364
TI  - After prison. The Samuel Gee lecture.

PMID- 8745363
TI  - Endothelium, for example.
AB  - Endothelial nitric oxide production contributes at many levels to cardiovascular
      efficiency (considered as tissue perfusion relative to cardiac work). Endothelial
      dysfunction is found in many conditions, including all known risk factors for
      atheroma, and is usually generalised, when present, involving microvessels as
      well as large arteries, impairing cardiovascular efficiency and potentially
      initiating atheroma. Loss of flow-related dilation is a manifestation of
      endothelial dysfunction and can be measured non-invasively, thereby providing a
      potential marker of reversible atherogenic susceptibility.

PMID- 8745365
TI  - Skillsharing. Joint statement from the Royal College of Physicians of London and
      the Royal College of Nursing.
AB  - For a number of years there has been a trend towards the sharing of skills, with
      their transfer from one group with which they have been traditionally associated
      to another within the health care professions. Examples in medicine include
      nurses delivering care to patients with diabetes mellitus, carrying out
      gastrointestinal endoscopy, administering intravenous chemotherapy to patients
      with cancer, and contributing to the management of patients with myocardial
      infarction and with asthma; opticians are employed in the screening of patients
      for glaucoma and diabetic retinopathy; and physiotherapy and radiography grew out
      of nursing. This movement is seen to be advantageous for patient care in that it
      extends the range and numbers of personnel. If this development is to be fostered
      and to continue to represent an advance in the delivery of health care, it is
      necessary to lay down guidelines to ensure that standards are maintained with
      safety and efficacy safeguarded. It was for this reason that representatives of
      the Royal Colleges of Nursing and of Physicians of London met to agree a set of
      principles that, while constructed for medicine and nursing, should be of general
      application to all the professions involved in providing health care.

PMID- 8745366
TI  - Audit of medical students' experiences of paediatric teaching: a tool to monitor
      and improve clinical teaching.
AB  - We provide clear aims and objectives for our students during their attachment in
      child health. To assess how well these are being met we reviewed their experience
      over the 3-year period 1991-1994. The audit was based on a questionnaire and was
      anonymous and voluntary; 45.4% of the students completed the questionnaire. These
      students' experiences were generally satisfactory and covered a wide variety of
      common childhood disorders. Of concern was that 32% of them received less than 1
      hour per week of teaching in protected time and that they seemed reluctant to
      avail themselves of the opportunity of attending casualty; 54% did not visit the
      casualty department at all during their attachment. We have identified several
      areas where improvements in our teaching can be made and we are confident that
      our system of regular audit constitutes a valuable tool to monitor and improve
      clinical teaching.

PMID- 8745367
TI  - Mediators of inflammation in response to air pollution: a focus on ozone and
      nitrogen dioxide.

PMID- 8745368
TI  - EUROSCREEN: ethical and philosophical issues of genetic screening in Europe.

PMID- 8745369
TI  - Meeting the challenge of change.

PMID- 8745370
TI  - Autologous blood transfusion.

PMID- 8745371
TI  - Infectious diseases: who cares and how much?

PMID- 8745372
TI  - The case for widening the referral system.
AB  - General practitioners (GPs) in the United Kingdom are vigorous in their defence
      of their sole right to refer a patient to a specialist. However, a strong case
      can be put for allowing access to specialist services through other channels of
      referral such as open access clinics, direct referral by district nurses,
      residential and nursing home managers or social workers. GPs and hospital
      consultants have long-established work patterns and are likely to be reluctant to
      change. But if all patients are to receive the level of expertise to which they
      are entitled, the barriers at the hospital/community frontier will have to come
      down.

PMID- 8745373
TI  - A hundred years of the Babinski reflex.

PMID- 8745374
TI  - The toxic effect of language on medicine.

PMID- 8745375
TI  - Brain stem death.

PMID- 8745377
TI  - Guillain-Barre syndrome: a pediatric challenge.

PMID- 8745378
TI  - Childhood Guillain-Barre syndrome: clinical presentation, diagnosis, and therapy.
AB  - A rapidly progressive, generally symmetric, ascending flaccid paraparesis or
      quadriparesis that develops in an infant or child constitutes an uncommon but
      important pediatric neurologic emergency that requires immediate evaluation and
      treatment. The differential diagnosis primarily includes acute neuropathies, most
      commonly the childhood Guillain-Barre syndrome and, rarely, acute transverse
      myelitis or infantile poliomyelitis. A clinical distinction may be difficult in
      the younger child in whom detailed sensory examination is not possible. Although
      most children with Guillain-Barre syndrome usually have a benign and relatively
      limited clinical illness, some become severely ill, requiring intubation and
      careful intensive monitoring. To date, no well-controlled multi-institutional
      studies of treatment with either plasmapheresis or intravenously administered
      immunoglobulin have been developed in children despite the success of these
      modalities in adults. A review of the data available using these therapies is
      included in this study.

PMID- 8745379
TI  - Dystrophinopathies: clarification and complication.
AB  - The purpose of this review is to analyze the clinical applications of a
      remarkable series of advances made in molecular genetics, primarily with regard
      to Becker muscular dystrophy. A new classification is required to clarify such
      syndromes as Duchenne and Becker muscular dystrophy. Dystrophinopathies can be
      seen in patients with early onset and a severe course (Duchenne muscular
      dystrophy), patients with later onset and milder weakness (Becker muscular
      dystrophy), patients with myalgia and cramp syndrome, and patients with dilated
      cardiomyopathies. Dystrophin testing in muscle is the most sensitive test for
      identification of dystrophinopathy patients, although gene deletion studies can
      make the diagnosis in most cases.

PMID- 8745380
TI  - Myalgia and cramps: dystrophinopathy with wide-ranging laboratory findings.
AB  - We present 12 cases of males with myalgia and cramps and a normal muscle strength
      examination. All the patients had muscle dystrophin values consistent with Becker
      muscular dystrophy. Five of the patients had a normal electromyogram, and five
      had normal light microscopic muscle biopsy results. Of particular note, four of
      the 12 patients had normal serum creatine kinase levels, and four others had only
      mild elevations (less than twice the upper limit of normal). These patients
      establish an identifiable dystrophinopathy of adolescent boys and young men that
      can present with muscle pain and, in some cases, normal routine laboratory
      evaluations.

PMID- 8745381
TI  - Neurologic and ophthalmologic findings in children exposed to cocaine in utero.
AB  - We studied a cohort of 73 children exposed to cocaine in utero to characterize
      the spectrum of neurologic and ophthalmologic abnormalities; 36 children with no
      documented in utero drug exposure were selected as a control group. Most
      referrals of cocaine-exposed children to the child neurologist were made in the
      1st year of life (81%). Reasons for referral were hypertonia (29%), seizures
      (22%), developmental delay (11%), tremulousness (11%), and hypotonia (4%). The
      most common abnormal finding in the cocaine-exposed children was
      hypertonia/hyperreflexia (63%), which was rarely seen in the control group. In
      addition, hypertonia/hyperreflexia was underdiagnosed by referring physicians.
      Similarly, hypotonia was seen on neurologic examination of cocaine-exposed
      children more frequently than documented by referral (16% versus 4%). Hypotonia
      was rarely seen in the control group. Twelve (43%) of 28 cocaine-exposed children
      seen by a pediatric ophthalmologist had structural ophthalmologic abnormalities.
      Neurologic and ophthalmologic findings suggesting structural lesions of the
      nervous system must be considered in cocaine-exposed children.

PMID- 8745382
TI  - Nitrazepam for refractory infantile spasms and the Lennox-Gastaut syndrome.
AB  - Infantile spasms and the Lennox-Gastaut syndrome are considered to be age
      specific pediatric epileptic syndromes and together constitute a significant
      percentage of medically resistant seizures in childhood. Twenty children, ages 4
      to 28 months (median, 12 months), with medically refractory infantile spasms or
      the Lennox-Gastaut syndrome, were treated with the investigational benzodiazepine
      nitrazepam in an open-label study. Daily dosage of nitrazepam ranged from 0.5 to
      3.5 mg/kg, with a median dosage of 1.5 mg/kg, divided into two doses per day.
      Side effects included pooling of oral secretions (12 children) and sedation (six
      children); however, no serious side effects were seen. Responses to nitrazepam
      were as follows: five complete responses (cessation of all seizures), seven
      partial responses (greater than 50% reduction of seizures), and eight with no
      response. Median duration of response was 9 months (range, 4 to 16 months) in
      children with infantile spasms and 14 months (range, 8 to 26 months) in children
      with the Lennox-Gastaut syndrome. Nitrazepam is an effective anticonvulsant in
      this small cohort of children with medically refractory infantile spasms and the
      Lennox-Gastaut syndrome, resulting in a 25% response rate and only modest side
      effects.

PMID- 8745383
TI  - Combination therapy of infantile spasms with high-dose pyridoxal phosphate and
      low-dose corticotropin.
AB  - A new combination therapy, high-dose pyridoxal phosphate (40 to 50 mg/kg daily)
      and low-dose corticotropin (0.01 mg [0.4 IU]/kg daily), was tried in 28 children
      with infantile spasms. Monotherapy with pyridoxal phosphate provided excellent
      seizure control in three (11%) of the 28 subjects. Corticotropin was subsequently
      added to the regimen of the remaining 25 patients. At 1 month after discontinuing
      corticotropin, 21 (84%) of the 25 patients experienced no seizures, and 22 (88%)
      of the 25 showed improvement in their electroencephalographic findings. The mean
      interval until achievement of seizure control was 4.1 days after the initiation
      of corticotropin. The outcome in the 21 patients has been followed for a mean
      period of 34.9 months (range, 2 to 81 months). Of these 21 patients, six (29%)
      have had relapses of infantile spasms, and 10 (48%) have experienced normal
      development. Transient increases in liver enzymes occurred in 14 (50%) of the 28
      patients, but none of the patients developed more serious side effects. The
      investigators conclude that combination therapy with high-dose pyridoxal
      phosphate and low-dose corticotropin is a promising new therapy.

PMID- 8745385
TI  - Etiologic classification of infantile spasms in 140 cases: role of positron
      emission tomography.
AB  - The classification of infantile spasms into symptomatic, cryptogenic, and
      idiopathic subgroups depends on clinical examination and available diagnostic
      technology. Positron emission tomography (PET) of glucose utilization is a
      powerful tool in detecting brain malformations (particularly cortical dysplasia)
      in infants with spasms. We analyzed etiologic data from 140 such infants, 78
      girls and 62 boys, ages 2 months to 4 years 10 months (mean, 17 months). All had
      been evaluated extensively in one of two major medical centers. It should be
      emphasized that our referral population is biased toward infants with intractable
      spasms who fail to show a structural lesion. Seven patients had neurocutaneous
      syndromes, two had chromosomal abnormalities, two had inborn errors of
      metabolism, and one each had craniosynostosis or Menkes syndrome. Computed
      tomography and/or magnetic resonance imaging detected lesions in another 29
      infants (20.7%) who did not have a specific disease or syndrome. Without the
      benefit of PET, the total number of symptomatic cases was 42 (30.0%). One infant,
      classified as idiopathic, had normal development and PET. In 97 cryptogenic
      cases, PET uncovered unifocal abnormalities in 30 and multifocal abnormalities in
      62. Diffuse PET abnormalities, which did not provide specific etiologic
      information, were seen in three infants. Another two infants had normal PET
      scans. Thus, with the benefit of PET, the number of symptomatic cases rose
      dramatically from 42 (30.0%) to 134 (95.7%). The majority of unifocal and
      multifocal abnormalities on PET are believed to represent dysplastic lesions.

PMID- 8745384
TI  - Valproic acid treatment of learning disorder and severely epileptiform EEG
      without clinical seizures.
AB  - Using a single-patient (n = 1) clinical trial, we studied a 7-year-old boy who
      presented with unsatisfactory progress in school and whose electroencephalogram
      had very active independent frontal spike discharges. He had not had clinical
      seizures. The patient was randomized to receive valproic acid, 125 mg twice
      daily, (four periods) or matching placebo (four periods) over 8 weeks. Primary
      endpoints were the Wechsler Intelligence Scale for Children-Revised Coding sub
      test and a handwriting sample. Behavior was monitored using teacher's and
      parent's Conners questionnaires. His score on the Wechsler Intelligence Scale for
      Children-Revised Coding subtest was significantly improved while he was taking
      valproic acid (P = .03). His electroencephalogram improved from a pretreatment
      recording of 28 spike discharges per minute to a normal recording while on
      valproic acid. We conclude that in this patient, valproic acid had a cognitive
      enhancing effect, probably by reducing epileptiform discharges.

PMID- 8745386
TI  - Outcome after open-heart surgery in infants and children.
AB  - We have studied the neurodevelopmental outcome of 104 consecutive unselected
      children who underwent open-heart surgery from 1987 through 1989. Survivors had
      formal neurologic and psychometric examinations after 2 years of age. Mean IQ was
      90, and 78% had scores above 70. Cerebral palsy occurred in 22%. Deep hypothermia
      for longer than 45 minutes was associated with IQ less than 85 (P < .001) and
      later cerebral palsy (P = .02). Those less than 1 month old at operation had a
      median IQ of 96, and 25% had cerebral palsy. Median IQ for survivors of
      hypoplastic left heart syndrome was 66, only one had an IQ above 70, and 57% had
      cerebral palsy. Median IQ for transposition of great arteries was 109, only one
      was less than 85, and all had normal neurologic examinations. Those between 1 and
      6 months of age at operation had a median IQ of 93, with 64% above 85, and 5% had
      cerebral palsy. Those older than 6 months had a median IQ of 99, with 70% above
      85, and 13% had cerebral palsy. For infants less than 1 month old at operation, a
      strong association existed between outcome, type of lesion, and duration of deep
      hypothermia (P < .01), although not in all cases. In those older than 1 month at
      operation, no association existed between outcome and any study variable.
      Although the majority of children have an uneventful outcome after open-heart
      surgery, a significant morbidity exists. This is related to several factors,
      including type of lesion and duration of hypothermia, particularly in neonates;
      preoperative congenital and acquired lesions; and possible perioperative
      cerebrovascular events.

PMID- 8745387
TI  - Medulloblastoma in a 7-year-old girl.

PMID- 8745388
TI  - Infantile onset of hereditary ascending spastic paralysis with bulbar
      involvement.
AB  - Primary lateral sclerosis and hereditary spastic paraparesis are both rare
      neurodegenerative disorders characterized by progressive weakness and spasticity
      of the lower limbs, with involvement of the corticospinal tracts and sparing of
      anterior horn cells. We describe a consanguineous family in which three sons
      developed progressive paralysis of the lower extremities in infancy with
      subsequent involvement of the upper extremities and bulbar muscles but cognitive
      sparing. This family presents the nosologic difficulty of distinguishing between
      hereditary spastic paraparesis and primary lateral sclerosis. We suggest that the
      diagnosis in this family is hereditary primary lateral sclerosis. This is the
      first instance of familial occurrence of primary lateral sclerosis.

PMID- 8745390
TI  - Amylaceous (polyglucosan) bodies in familial cerebral atrophy of early onset.
AB  - An 8-year-old girl and her 4-year-old sister presented with psychomotor
      retardation during the 1st year of life. This was followed by spasticity,
      seizures, and in the older patient, progressive loss of faculties and death.
      Computed tomographic and magnetic resonance imaging scans demonstrated
      progressive cerebral atrophy in both patients. Postmortem examination in the
      older sibling showed diffuse atrophy of the supragranular layers of the cerebral
      cortex, atrophy and gliosis of the white matter, and accumulation of numerous
      amylaceous (polyglucosan) bodies within the cytoplasm of cell processes. The
      inclusions were closely associated with atrophy of the parenchyma. The findings
      suggest that this disorder is different from other childhood diseases in which
      amylaceous bodies accumulate within the brain.

PMID- 8745391
TI  - Neurologic findings in children and adults with Williams syndrome.
AB  - Twenty-four children with Williams syndrome underwent systematic neurologic
      evaluations. Abnormalities of mental status, motor coordination, tone, and gait
      were most prevalent. Tone abnormalities varied as a function of age, with younger
      children frequently exhibiting decreased tone and older subjects almost
      exclusively having increased tone. The gait and coordination abnormalities
      persisted among older subjects, indicating that they were not simply maturational
      problems. Physicians caring for such youngsters need to be aware that a variety
      of neurologic abnormalities are common in Williams syndrome and may change or
      progress over time. Neurologic examinations that reveal findings beyond the
      typical pattern that we report may raise suspicion for added neurologic insult
      and warrant further investigation.

PMID- 8745392
TI  - Physicians' attitudes regarding Down syndrome.
AB  - We conducted a representative survey to obtain current information about
      attitudes of pediatricians, child neurologists, and pediatric surgeons in Hungary
      regarding Down syndrome. The findings are compared to those of a similar study
      from Canada. In the treatment of mentally handicapped newborns, none of the
      Hungarian doctors would choose active euthanasia; only a few percent would
      perform passive euthanasia. Hungarian doctors give priority to the hospital-based
      ethical committee in the decision-making process regarding the treatment versus
      nontreatment of a newborn with major congenital anomalies. In contrast to the
      Canadians, only a few doctors would discuss this question with parents and
      nurses. Most Hungarian physicians are not aware of legal regulations in this
      field. These attitudes can be explained by religious and cultural traditions
      different from the Canadian and Western European standards. The Hungarian medical
      community, like other Eastern European countries, is much more authoritative than
      the Canadian system. Furthermore, the appropriate legal regulations are not yet
      properly codified.

PMID- 8745393
TI  - Homocystinuria presenting with sagittal sinus thrombosis in infancy.

PMID- 8745394
TI  - Severe central nervous system involvement in a patient with congenital fiber-type
      disproportion myopathy.

PMID- 8745395
TI  - The protein machinery of vesicle budding and fusion.
AB  - A general protein machinery that buds and fuses transport vesicles is harnessed
      to generate the complex web of intracellular transport pathways critical for such
      diverse processes as cell growth, endocytosis, hormone release, and
      neurotransmission. With this appreciation, the challenge of understanding the
      precise molecular mechanisms of these many facets of cell biology has been
      reduced to a series of problems in protein structure and chemistry.

PMID- 8745396
TI  - Structural resiliency of an EGF-like subdomain bound to its target protein,
      thrombin.
AB  - The thrombin-bound structures of native peptide fragments from the fifth EGF-like
      domain of thrombomodulin were determined by use of NMR and transferred NOE
      spectroscopy. The bound peptides assume an EGF-like structure of an antiparallel
      beta-sheet, a novel structural motif observed for a bound peptide in protein
      peptide complexes. There is a remarkable structural resiliency of this structure
      motif manifested in its ability to accommodate a different number of residues
      within the disulfide loop. Docking experiments revealed that the key contacts
      with thrombin are hydrophobic interactions between the side chains of residues
      Ile 414 and Ile 424 of thrombomodulin and a hydrophobic pocket on the thrombin
      surface. Residues Leu 415, Phe 419, and Ile 420, which would have been buried in
      intact EGF-like domains, are unfavorably exposed in the complex of thrombin with
      the EGF-like thrombomodulin fragment, thus providing a rationale for the
      enhancement of binding affinity upon the deletion of Ile 420. The unique beta
      sheet structures of the bound peptides are specified by the presence of disulfide
      bridges in the peptides because a corresponding linear thrombomodulin fragment
      folds into a sheet structure with a different backbone topology. The different
      bound conformations for the linear and the cyclized peptides indicate that side
      chain interactions within a specific environment may dictate the folding of bound
      peptides in protein-peptide complexes.

PMID- 8745397
TI  - Are turns required for the folding of ribonuclease T1?
AB  - Ribonuclease T1 (RNase T1) is a small, globular protein of 104 amino acids for
      which extensive thermodynamic and structural information is known. To assess the
      specific influence of variations in amino acid sequence on the mechanism for
      protein folding, circularly permuted variants of RNase T1 were constructed and
      characterized in terms of catalytic activity and thermodynamic stability. The
      disulfide bond connecting Cys-2 and Cys-10 was removed by mutation of these
      residues to alanine (C2, 10A) to avoid potential steric problems imposed by the
      circular permutations. The original amino-terminus and carboxyl-terminus of the
      mutant (C2, 10A) were subsequently joined with a tripeptide linker to accommodate
      a reverse turn and new termini were introduced throughout the primary sequence in
      regions of solvent-exposed loops at Ser-35 (cp35S1), Asp-49 (cp49D1), Gly-70
      (cp70G1), and Ser-96 (cp96S1). These circularly permuted RNase T1 mutants
      retained 35-100% of the original catalytic activity for the hydrolysis of
      guanylyl(3'-->5')cytidine, suggesting that the overall tertiary fold of these
      mutants is very similar to that of wild-type protein. Chemical denaturation
      curves indicated thermodynamic stabilities at pH 5.0 of 5.7, 2.9, 2.6, and 4.6
      kcal/mol for cp35S1, cp49D1, cp70G1, and cp96S1, respectively, compared to a
      value of 10.1 kcal/mol for wild-type RNase T1 and 6.4 kcal/mol for (C2, 10A) T1.
      A fifth set of circularly permuted variants was attempted with new termini
      positioned in a tight beta-turn between Glu-82 and Gln-85. New termini were
      inserted at Asn-83 (cp83N1), Asn-84 (cp84N1), and Gln-85 (cp85Q1). No detectable
      amount of protein was ever produced for any of the mutations in this region,
      suggesting that this turn may be critical for the proper folding and/or
      thermodynamic stability of RNase T1.

PMID- 8745398
TI  - PROMOTIF--a program to identify and analyze structural motifs in proteins.
AB  - We describe a suite of programs, PROMOTIF, that analyzes a protein coordinate
      file and provides details about the structural motifs in the protein. The program
      currently analyzes the following structural features: secondary structure; beta
      and gamma-turns; helical geometry and interactions; beta-strands and beta-sheet
      topology; beta-bulges; beta-hairpins; beta-alpha-beta units and psi-loops;
      disulphide bridges; and main-chain hydrogen bonding patterns. PROMOTIF creates
      postscript files showing the examples of each type of motif in the protein, and a
      summary page. The program can also be used to compare motifs in a group of
      related structures, such as an ensemble of NMR structures.

PMID- 8745399
TI  - Crystallographic determination of the structures of human alpha-thrombin
      complexed with BMS-186282 and BMS-189090.
AB  - The crystallographic structures of the ternary complexes of human alpha-thrombin
      with hirugen (a sulfated hirudin fragment) and the small-molecule active site
      thrombin inhibitors BMS-186282 and BMS-189090 have been determined at 2.6 and 2.8
      A. In both cases, the inhibitors, which adopt very similar bound conformations,
      bind in an antiparallel beta-strand arrangement relative to the thrombin main
      chain in a manner like that reported for PPACK, D-Phe-Pro-Arg-CH2Cl. They do,
      however, exhibit differences in the binding of the alkyl guanidine moiety in the
      specificity pocket. Numerous hydrophilic and hydrophobic interactions serve to
      stabilize the inhibitors in the binding pocket. Although PPACK forms covalent
      bonds to both serine and the histidine of the catalytic triad of thrombin,
      neither BMS-186282 nor BMS-189090 bind covalently and only BMS-186282 forms a
      hydrogen bond to the serine of the catalytic triad. Both inhibitors bind with
      high affinity (Ki = 79 nM and 3.6 nM, respectively) and are highly selective for
      thrombin over trypsin and other serine proteases.

PMID- 8745400
TI  - Active site properties of monomeric triosephosphate isomerase (monoTIM) as
      deduced from mutational and structural studies.
AB  - MonoTIM is a stable monomeric variant of the dimeric trypanosomal enzyme triose
      phosphate isomerase (TIM) with less, but significant, catalytic activity. It is
      known that in TIM, three residues, Lys 13 (loop 1), His 95 (loop 4), and Glu 167
      (loop 6) are the crucial catalytic residues. In the wild-type TIM dimer, loop 1
      and loop 4 are very rigid because of tight interactions with residues of the
      other subunit. Previous structural studies indicate that Lys 13 and His 95 have
      much increased conformational flexibility in monoTIM. Using site-directed
      mutagenesis, it is shown here that Lys 13 and His 95 are nevertheless essential
      for optimal catalysis by monoTIM: monoTIM-K13A is completely inactive, although
      it can still bind substrate analogues, and monoTIM-H95A is 50 times less active.
      The best inhibitors of wild-type TIM are phosphoglycolohydroxamate (PGH) and 2
      phosphoglycolate (2PG), with KI values of 8 microM and 26 microM, respectively.
      The affinity of the monoTIM active site for PGH has been reduced approximately 60
      fold, whereas for 2PG, only a twofold weakening of affinity is observed. The mode
      of binding, as determined by protein crystallographic analysis of these substrate
      analogues, shows that, in particular, 2PG interacts with Lys 13 and His 95 in a
      way similar but not identical to that observed for the wild-type enzyme. This
      crystallographic analysis also shows that Glu 167 has the same interactions with
      the substrate analogues as in the wild type. The data presented suggest that,
      despite the absence of the second subunit, monoTIM catalyzes the interconversion
      of D-glyceraldehyde-3-phosphate and dihydroxyacetone phosphate via the same
      mechanism as in the wild type.

PMID- 8745401
TI  - Structure-based modeling of the ligand binding domain of the human cell surface
      receptor CD23 and comparison of two independently derived molecular models.
AB  - CD23, a type II membrane receptor protein, recognizes four different ligands via
      its extracellular C-type lectin domain: immunoglobulin E (IgE), CD21, and the
      beta 2-integrins CD11b and CD11c. CD23 specifically interacts in a calcium
      dependent manner, "lectin-like" with carbohydrate moieties expressed on CD21 and
      CD11b/c, but also "lectin-unlike" with protein epitopes on IgE. As a first step
      in analyzing the multiple binding specificities associated with CD23 in more
      detail, we report a detailed molecular model of the lectin-like domain of human
      CD23 (hCD23). The model was built based on information provided by X-ray
      structures of mannose binding protein (MBP) and E-selectin, both of which are
      members of the calcium-dependent (C-type) lectin superfamily. Sequence-structure
      comparisons suggest that hCD23 is structurally more similar to MBP than to E
      selectin. The hCD23 model is compared to an independently derived model. Although
      the CD23-carbohydrate and CD23-protein interactions are both calcium dependent,
      analysis of the model suggests the presence of distinct binding sites for these
      ligands.

PMID- 8745402
TI  - Identification of the residues responsible for the alkaline inhibition of Cu,Zn
      superoxide dismutase: a site-directed mutagenesis approach.
AB  - The catalytic rate of wild type, two single (Lys 120-->Leu, Lys 134-->Thr), and
      one double (Lys 120-->Leu-Lys 134-->Thr) mutants of Xenopus laevis B Cu,Zn
      superoxide dismutase has been studied by pulse radiolysis as a function of pH.
      The pH dependence curve of the wild-type enzyme can be deconvoluted by two
      deprotonation equilibria, at pH 9.3 (pK1) and at pH 11.3 (pK2). Catalytic rate
      measurements on single and double mutants indicate that pK1 is mainly due to the
      deprotonation of Lys 120 and Lys 134, with only a minor contribution from other
      surface basic residues, whereas pK2 is due to titration of the invariant Arg 141,
      likely coupled to deprotonation of the copper-bound water molecule. Accordingly,
      Brownian dynamics simulations carried out as a function of pH reproduce well the
      pH dependence of the catalytic rate, when the experimentally determined pKs are
      assigned to Lys 120, Lys 134, and Arg 141.

PMID- 8745403
TI  - Folding proteins with a simple energy function and extensive conformational
      searching.
AB  - We describe a computer algorithm for predicting the three-dimensional structures
      of proteins using only their amino acid sequences. The method differs from others
      in two ways: (1) it uses very few energy parameters, representing hydrophobic and
      polar interactions, and (2) it uses a new "constraint-based exhaustive" searching
      method, which appears to be among the fastest and most complete search methods
      yet available for realistic protein models. It finds a relatively small number of
      low-energy conformations, among which are native-like conformations, for crambin
      (1CRN), avian pancreatic polypeptide (1PPT), melittin (2MLT), and apamin. Thus,
      the lowest-energy states of very simple energy functions may predict the native
      structures of globular proteins.

PMID- 8745404
TI  - Yeast heat shock transcription factor N-terminal activation domains are
      unstructured as probed by heteronuclear NMR spectroscopy.
AB  - The structure and dynamics of the N-terminal activation domains of the yeast heat
      shock transcription factors of Kluyveromyces lactis and Saccharomyces cerevisiae
      were probed by heteronuclear 15N[1H] correlation and 15N[1H] NOE NMR studies.
      Using the DNA-binding domain as a structural reference, we show that the protein
      backbone of the N-terminal activation domain undergoes rapid, large-amplitude
      motions and is therefore unstructured. Difference CD data also show that the N
      terminal activation domain remains random-coil, even in the presence of DNA.
      Implications for a "polypeptide lasso" model of transcriptional activation are
      discussed.

PMID- 8745405
TI  - Covalent tethering of the dimer interface annuls aggregation in thymidylate
      synthase.
AB  - Thymidylate synthase (TS), a dimeric enzyme, forms large soluble aggregates at
      concentrations of urea (3.3-5M), well below that required for complete
      denaturation, as established by fluorescence and size-exclusion chromatography.
      In contrast to the wild-type enzyme, an engineered mutant of TS
      (T155C/E188C/C244T), TSMox, in which two subunits are crosslinked by disulfide
      bridges between residues 155-188' and 188-155' does not show this behavior.
      Aggregation behavior is restored upon disulfide bond reduction in the mutant
      protein, indicating the involvement of interface segments in forming soluble
      associated species. Intermolecular disulfide crosslinking has been used as a
      probe to investigate the formation of larger non-native aggregates. The studies
      argue for the formation of large multimeric species via a sticky patch of
      polypeptide from the dimer interface region that becomes exposed on partial
      unfolding. Covalent reinforcement of relatively fragile protein-protein
      interfaces may be a useful strategy in minimizing aggregation of non-native
      structures in multimeric proteins.

PMID- 8745406
TI  - Chemical crosslinking of the subunits of HIV-1 reverse transcriptase.
AB  - The reverse transcriptase (RT) of the human immunodeficiency virus type 1 (HIV-1)
      is composed of two subunits of 66 and 51 kDa in a 1 to 1 ratio. Because
      dimerization is a prerequisite for enzymatic activity, interference with the
      dimerization process could constitute an alternative antiviral strategy for RT
      inhibition. Here we describe an in vitro assay for the study of the dimerization
      state of HIV-1 reverse transcriptase based on chemical crosslinking of the
      subunits with dimethylsuberimidate. Crosslinking results in the formation of
      covalent bonds between the subunits, so that the crosslinked species can be
      resolved by denaturing gel electrophoresis. Crosslinked RT species with molecular
      weight greater than that of the dimeric form accumulate during a 1-15-min time
      course. Initial evidence suggests that those high molecular weight species
      represent trimers and tetramers and may be the result of intramolecular
      crosslinking of the subunits of a higher-order RT oligomer. A peptide that
      corresponds to part of the tryptophan repeat motif in the connection domain of
      HIV-1 RT inhibits crosslink formation as well as enzymatic activity. The
      crosslinking assay thus allows the investigation of the effect of inhibitors on
      the dimerization of HIV-1 RT.

PMID- 8745407
TI  - Second-site suppression of regulatory phosphorylation in Escherichia coli
      isocitrate dehydrogenase.
AB  - Inactivation of Escherichia coli isocitrate dehydrogenase upon phosphorylation at
      S113 depends upon the direct electrostatic repulsion of the negatively charged
      gamma-carboxylate of isocitrate by the negatively charged phosphoserine. The
      effect is mimicked by replacing S113 with aspartate or glutamate, which reduce
      performance (kcat/K(i).isocitrat/ Km.NADP) by a factor of 10(7). Here, we
      demonstrate that the inactivating effects of the electrostatic repulsion are
      completely eliminated by a second-site mutation, and provide the structural basis
      for this striking example of intragenic suppression. N115 is adjacent to S113 on
      one face of the D-helix, interacts with isocitrate and NADP+, and has been
      postulated to serve in both substrate binding and in catalysis. The single N115L
      substitution reduces affinity for isocitrate by a factor of 50 and performance by
      a factor of 500. However, the N115L substitution completely suppresses the
      inactivating electrostatic effects of S113D or S113E: the performance of the
      double mutants is 10(5) higher than the S113D and S113E single mutants. These
      mutations have little effect on the kinetics of alternative substrates, which
      lack the charged gamma-carboxylate of isocitrate. Both glutamate and aspartate at
      site 113 remain fully ionized in the presence of leucine. In the crystal
      structure of the N115L mutant, the leucine adopts a different conformer from the
      wild-type asparagine. Repacking around the leucine forces the amino-terminus of
      the D-helix away from the rest of the active site. The hydrogen bond between E113
      and N115 in the S113E single mutant is broken in the S113E/N115L mutant, allowing
      the glutamate side chain to move away from the gamma-carboxylate of isocitrate.
      These movements increase the distance between the carboxylates, diminish the
      electrostatic repulsion, and lead to the remarkably high activity of the
      S113E/N115L mutant.

PMID- 8745408
TI  - Structural coupling of the inhibitory regions flanking the ETS domain of murine
      Ets-1.
AB  - Several members of the ets gene family of transcription factors show negative
      regulation of DNA binding by intramolecular interactions. A structural mechanism
      for this auto-inhibition is investigated using a 161-residue N-terminal deletion
      mutant of murine Ets-1, Ets-1 delta N280. This protein shows a similar reduced
      affinity for DNA as native Ets-1 because it contains the ETS domain in context of
      the flanking amino- and carboxy-terminal regions that together mediate repression
      of DNA binding. The secondary structure of Ets-1 delta N280 was determined using
      NMR chemical shift, NOE, J coupling, and amide hydrogen exchange information. In
      addition to the winged helix-turn-helix ETS domain, Ets-1 delta N280 contains two
      alpha-helices in the amino-terminal inhibitory region and one alpha-helix in the
      carboxy-terminal inhibitory region. Chemical shift comparisons were made between
      this protein and an activated form of Ets-1 lacking the amino-terminal inhibitory
      region. The spectral differences demonstrate that the amino- and carboxy-terminal
      inhibitory sequences are structurally coupled to one another, thus explaining the
      observation that both regions are required for the repression of DNA binding.
      Furthermore, these data show that the inhibitory sequences also interact directly
      with the first helix of the intervening ETS domain, thereby providing a pathway
      for the repression of DNA binding. These results lead to a model of an inhibitory
      module in Ets-1 composed of both the amino- and carboxy-terminal regions
      interfaced with the ETS domain. This establishes the structural framework for
      understanding the intramolecular inhibition of Ets-1 DNA binding.

PMID- 8745409
TI  - Equilibrium dissociation and unfolding of the dimeric human papillomavirus strain
      16 E2 DNA-binding domain.
AB  - The equilibrium unfolding reaction of the C-terminal 80-amino-acid dimeric DNA
      binding domain of human papillomavirus (HPV) strain 16 E2 protein has been
      investigated using fluorescence, far-UV CD, and equilibrium sedimentation. The
      stability of the HPV-16 E2 DNA-binding domain is concentration-dependent, and the
      unfolding reaction is well described as a two-state transition from folded dimer
      to unfolded monomer. The conformational stability of the protein, delta GH2O, was
      found to be 9.8 kcal/mol at pH 5.6, with the corresponding equilibrium
      unfolding/dissociation constant, Ku, being 6.5 x 10(-8) M. Equilibrium
      sedimentation experiments give a Kd of 3.0 x 10(-8) M, showing an excellent
      agreement between the two different techniques. Denaturation by temperature
      followed by the change in ellipticity also shows a concomitant disappearance of
      secondary and tertiary structures. The Ku changes dramatically at physiologically
      relevant pH's: with a change in pH from 6.1 to 7.0, it goes from 5.5 x 10(-8) M
      to 4.4 x 10(10) M. Our results suggest that, at the very low concentration of
      protein where DNA binding is normally measured (e.g., 10(-11) M), the protein is
      predominantly monomeric and unfolded. They also stress the importance of the
      coupling between folding and DNA binding.

PMID- 8745410
TI  - Reconstitution of active octameric mitochondrial creatine kinase from two
      genetically engineered fragments.
AB  - Creatine kinase (CK) has been postulated to consist of two flexibly hinged
      domains. A previously demonstrated protease-sensitive site in M-CK (Morris &
      Jackson, 1991) has directed our attempts to dissect mitochondrial CK (Mi-CK) into
      two protein fragments encompassing amino acids [1-167] and [168-380]. When
      expressed separately in Escherichia coli, the two fragments yielded large amounts
      of insoluble inclusion bodies, from which the respective polypeptides could be
      purified by a simple two-step procedure. In contrast, co-expression of the two
      fragments yielded a soluble, active, and correctly oligomerizing enzyme. This
      discontinuous CK showed nearly full specific activity and was virtually
      indistinguishable from native Mi-CK by far- and near-UV CD. However, the positive
      cooperativity of substrate binding was abolished, suggesting a role of the
      covalent domain linkage in the crosstalk between the substrate binding sites for
      ATP and creatine. The isolated C-terminal fragment refolded into a native-like
      conformation in vitro, whereas the N-terminal fragment was largely unfolded.
      Prefolded [168-380] interacted in vitro with [1-167] to form an active enzyme.
      Kinetic analysis indicated that the fragments associate rapidly and with high
      affinity (1/K1 = 17 microM) and then isomerize slowly to an active enzyme (k2 =
      0.12 min-1; k-2 = 0.03 min-1). Our data suggest that the C-terminal fragment of
      Mi-CK represents an autonomous folding unit, and that the folding of the C
      terminal part might precede the conformational stabilization of the N-terminal
      moiety in vivo.

PMID- 8745411
TI  - Posttranslational processing of recombinant human interferon-gamma in animal
      expression systems.
AB  - We have characterized the heterogeneity of recombinant human interferon-gamma
      (IFN-gamma) produced by three expression systems: Chinese hamster ovary cells,
      the mammary gland of transgenic mice, and baculovirus-infected Spodopera
      frugiperda (Sf9) insect cells. Analyses of whole IFN-gamma proteins by
      electrospray ionization-mass spectrometry (ESI-MS) from each recombinant source
      revealed heterogeneous populations of IFN-gamma molecules resulting from
      variations in N-glycosylation and C-terminal polypeptide cleavages. A series of
      more specific analyses assisted interpretation of maximum entropy deconvoluted
      ESI-mass spectra of whole IFN-gamma proteins; MALDI-MS analyses of released,
      desialylated N-glycans and of deglycosylated IFN-gamma polypeptides were combined
      with analyses of 2-aminobenzamide labeled sialylated N-glycans by cation-exchange
      high-performance liquid chromatography. These analyses enabled identification of
      specific polypeptide cleavage sites and characterization of associated N-glycans.
      Production of recombinant IFN-gamma in the mammalian expression systems yielded
      polypeptides C-terminally truncated at dibasic amino acid sites. Mammalian cell
      derived IFN-gamma molecules displayed oligosaccharides with monosaccharide
      compositions equivalent to complex, sialylated, or high-mannose type N-glycans.
      In contrast, IFN-gamma derived from baculovirus-infected Sf9 insect cells was
      truncated further toward the C-terminus and was associated with neutral
      (nonsialylated) N-glycans. These data demonstrate the profound influence of host
      cell type on posttranslational processing of recombinant proteins produced in
      eukaryotic systems.

PMID- 8745412
TI  - Determinants of performance in the isocitrate dehydrogenase of Escherichia coli.
AB  - The substrate specificity of the NADP-dependent isocitrate dehydrogenase of
      Escherichia coli was investigated by combining site-directed mutagenesis and
      utilization of alternative substrates. A comparison of the kinetics of the wild
      type enzyme with 2R-malate reveals that the gamma-carboxylate of 2R,3S-isocitrate
      contributes a factor of 12,000,000 to enzyme performance. Analysis of kinetic
      data compiled for 10 enzymes and nine different substrates reveals that a factor
      of 1,650 can be ascribed to the hydrogen bond formed between S113 and the gamma
      carboxylate of bound isocitrate, a factor of 150 to the negative charge of the
      gamma-carboxylate, and a factor of 50 for the gamma-methyl. These results are
      entirely consistent with X-ray structures of Michaelis complexes that show a
      hydrogen bond positions the gamma-carboxylate of isocitrate so that a salt bridge
      can form to the nicotinamide ring of NADP.

PMID- 8745413
TI  - Computational method for relative binding energies of enzyme-substrate complexes.
AB  - A computational method for estimating the relative binding free energies of
      enzyme-substrate complexes is described that combines electrostatic and solvation
      models and X-ray crystallographic data. The polar contribution is evaluated by
      the Poisson-Boltzman equation. The nonpolar contribution is evaluated by solvent
      transfer data and surface area calculations. This algorithm was used to calculate
      the relative binding energies of 63 pairs of nine different mutant proteins with
      seven different substituted R-malate substrates of Escherichia coli isocitrate
      dehydrogenase. Comparison of calculated values with the experimentally observed
      values shows a high degree of correlation.

PMID- 8745414
TI  - BSTI, a trypsin inhibitor from skin secretions of Bombina bombina related to
      protease inhibitors of nematodes.
AB  - From skin secretions of the European frog Bombina bombina, a new peptide has been
      isolated that contains 60 amino acids, including 10 cysteine residues. Its
      sequence was determined by automated Edman degradation and confirmed by analysis
      of the cDNA encoding the precursor. A search in the databanks demonstrated that
      the pattern of cysteine residues in this skin peptide is similar to the ones
      found in protease inhibitors from Ascaris and in a segment of human von
      Willebrand factor. The 3D structure of the trypsin inhibitor from Ascaris suum
      could be used as a template to build a model of the amphibian peptide. In
      addition, we have demonstrated that this constituent of skin secretion is indeed
      an inhibitor of trypsin and thrombin, with K(i) values in the range of 0.1 to 1
      microM. The new peptide was thus named BSTI for Bombina skin trypsin/thrombin
      inhibitor.

PMID- 8745415
TI  - Topology prediction of membrane proteins.
AB  - A new method is described for prediction of protein membrane topology (intra- and
      extracellular sidedness) from multiply aligned amino acid sequences after
      determination of the membrane-spanning segments. The prediction technique relies
      on residue compositional differences in the protein segments exposed at each side
      of the membrane. Intra/extracellular ratios are calculated for the residue types
      Asn, Asp, Gly, Phe, Pro, Trp, Tyr, and Val, preferably found on the extracellular
      side, and for Ala, Arg, Cys, and Lys, mostly occurring on the intracellular side.
      The consensus over these 12 residue distributions is used for sidedness
      prediction. The method was developed with a test set of 42 protein families, for
      which all but one were correctly predicted with the new algorithm. This
      represents an improvement over predictions based on the widely used "positive
      inside rule" and other techniques, where at least six mispredictions were
      observed for the same data set. Further, application of this and other methods to
      12 protein families not in the test set still showed the better performance of
      the present technique, which was subsequently applied to another set of membrane
      protein families where the topology has yet to be determined.

PMID- 8745416
TI  - On the role of surface tension in the stabilization of globular proteins.
AB  - The stabilization of proteins by a variety of co-solvents can be related to their
      property of increasing the surface tension of water. It is demonstrated that,
      during the thermal unfolding of proteins, this increase of the surface tension
      can be overcome by the increase in the temperature of the solution at the
      midpoint of the transition, Tm, and the weak binding of co-solvent molecules.
      Three such co-solvents were studied: trehalose, lysine hydrochloride (LysHCl),
      and arginine hydrochloride (ArgHCl). Trehalose and LysHCl increase the midpoint
      of Tm. The increase of the surface tension by addition of trehalose is completely
      compensated by its decrease due to the increase in Tm. However, for LysHCl, the
      increase of the surface tension by the co-solvent is partly reduced by its
      binding to the protein. For trehalose, preferential interaction measurements with
      RNaseA demonstrate that it is totally excluded from the protein. In contrast,
      LysHCl gives evidence of binding to RNaseA. ArgHCl also increases the surface
      tension of water. Nevertheless, Tm of RNaseA decreases on addition of ArgHCl to
      the solution. Preferential interaction measurements showed very small values of
      preferential hydration of the native protein, indicating extensive binding of
      ArgHCl to the protein. During unfolding, the amount of additional ArgHCl binding
      is sufficiently large to counteract the surface tension effects, and the protein
      is destabilized. Therefore, although surface tension appears to be a critical
      factor in the stabilization of proteins, its increase by co-solvent does not
      ensure increased stabilization. The binding of ligands can reduce significantly,
      or even overwhelm, its effects.

PMID- 8745418
TI  - Calorimetric studies of biopolymers.

PMID- 8745417
TI  - Woodward's reagent K inactivation of Escherichia coli L-threonine dehydrogenase:
      increased absorbance at 340-350 nm is due to modification of cysteine and
      histidine residues, not aspartate or glutamate carboxyl groups.
AB  - L-Threonine dehydrogenase (TDH) from Escherichia coli is rapidly inactivated and
      develops a new absorbance peak at 347 nm when incubated with N-ethyl-5
      phenylisoxazolium-3'-sulfonate (Woodward's reagent K, WRK). The cofactors, NAD+
      or NADH (1.5 mM), provide complete protection against inactivation; L-threonine
      (60 mM) is approximately 50% as effective. Tryptic digestion of WRK-modified TDH
      followed by HPLC fractionation (pH 6.2) yields four 340-nm-absorbing peptides,
      two of which are absent from enzyme incubated with WRK and NAD+. Peptide I has
      the sequence TAICGTDVH (TDH residues 35-43), whereas peptide II is TAICGTDVHIY
      (residues 35-45). Peptides not protected are TMLDTMNHGGR (III, residues 248-258)
      and NCRGGRTHLCR (IV, residues 98-108). Absorbance spectra of these WRK-peptides
      were compared with WRK adducts of imidazole, 2-hydroxyethanethiolate, and
      acetate. Peptides III and IV have pH-dependent lambda max values (340-350 nm),
      consistent with histidine modification. Peptide I has pH-independent lambda max
      (350 nm) indicating that a thiol is modified. WRK, therefore, does not react
      specifically with carboxyl groups in this enzyme, but rather modifies Cys-38 in
      the active site of TDH; modification of His-105 and His-255 does not affect
      enzyme activity. These results are the first definitive proof of WRK modifying
      cysteine and histidine residues of a protein and show that enzyme inactivation by
      WRK associated with the appearance of new absorptivity at 340-350 nm does not
      establish modification of aspartate or glutamate residues, as has been assumed in
      numerous earlier reports.

PMID- 8745419
TI  - Crystallization of a soluble form of the Kex1p serine carboxypeptidase from
      Saccharomyces cerevisiae.
AB  - A soluble form of the killer factor and prohormone-processing carboxypeptidase,
      "Kex1 delta p," from Saccharomyces cerevisiae, has been crystallized in 17-22%
      poly(enthylene glycol) methyl ether (average M(r) = 5,000), 100 mM ammonium
      acetate, 5% glycerol, pH 6.5, at 20 degrees C. A native data set (2.8 A
      resolution) and four derivative data sets (3.0-3.2 A resolution) were collected
      at the Photon Factory (lambda = 1.0 A). The crystals belong to space group
      P2(1)2(1)2(1) with a =56.6 A, b = 84.0 A, c = 111.8 A. Freezing a Kex1 delta p
      crystal has facilitated the collection of a 2.4-A data set using a rotating anode
      source (lambda = 1.5418 A). Molecular replacement models have been built based on
      the structures of wheat serine carboxypeptidase (CPDW-II; Liao DI et al., 1992,
      Biochemistry 31:9796-9812) and yeast carboxypeptidase Y.

PMID- 8745420
TI  - State-dependent life history evolution in Soay sheep: dynamic modelling of
      reproductive scheduling.
AB  - Adaptive decisions concerning the scheduling of reproduction in an animal's
      lifetime, including age at maturity and clutch or litter size, should depend on
      an animal's body condition or state. In this state-dependent case, we are
      concerned with the optimization of sequences of actions and so dynamic
      optimization techniques are appropriate. Here we show how stochastic dynamic
      programming can be used to study the reproductive strategies and population
      dynamics of natural populations, assuming optimal decisions. As examples we
      describe models based upon field data from an island population of Soay sheep on
      St. Kilda. This population shows persistent instability, with cycles culminating
      in high mortality every three or four years. We explore different assumptions
      about the extent to which Soay ewes use information about the population cycle in
      making adaptive decisions. We compare the observed distributions of strategies
      and population dynamics with model predictions; the results indicate that Soay
      ewes make optimal reproductive decisions given that they have no information
      about the population cycle. This study represents the first use of a dynamic
      optimization life history model of realistic complexity in the study of a field
      population. The techniques we use are potentially applicable to many other
      populations, and we discuss their extension to other species and other life
      history questions.

PMID- 8745421
TI  - To what extent does a given heart rate correlate with following heart rates in
      the developing human fetus?
AB  - To quantitatively determine the extent to which a given heart rate correlates
      with the following heart rate(s) at any gestational age, we studied 181
      uncomplicated human fetuses between 23 and 41 weeks gestation. A continuous 90
      120 min observation was made for each case using external Doppler-ultrasound
      cardiotocography. For every individual fetal heart rate dataset, 'probability
      distribution matrices' were calculated with fetal heart rates (termed FHRs) at 1
      beat/min (bpm) intervals, and the beat-to-beat(s) difference (termed DFHRn: 1 <
      or = n < or = 1000), also at 1-bpm intervals arranged in rows and columns,
      respectively, with probability in each element. Using 'piecewise linear
      regression', (1) the difference between the DFHR1 (n = 1) probability
      distribution matrix as the 'control' and a given DFHRn (n > or = 2) probability
      matrix as the 'variable', was analyzed to obtain the statistically critical
      point(s) (termed 'beat-delay' in beats) for each fetus, and (2) a scattergram of
      'beat-delay' vs. gestational age-group, made from all fetuses studied, was
      analyzed to reveal any critical age(s) in gestation. One statistically
      significant point was evident at 28-29 weeks gestation. During the period prior
      to the critical point, a linear decrement in 'beat-delay' with 21 beats (mean) at
      23-25 weeks to 11 beats at 28-29 weeks gestation was noted, suggesting that the
      conduction system-oriented heart beat gradually comes under functional control of
      the autonomic nervous system as well as under possible regulation by the
      maturating medulla oblongata. From the critical point, through to term, there was
      no significant change in 'beat-delay' ranging from 7-11 beats, thereby implying
      that the fetal heart rate becomes stabilized as a result of the control rendered
      by the more developed autonomic nervous system function. Whether or not brain
      function cephalad to the medulla oblongata actually participates in this
      phenomenon remains to be elucidated.

PMID- 8745422
TI  - Doppler assessment of umbilical flow after genetic amniocentesis.
AB  - The aim of our study was to evaluate the immediate changes on the fetal heart
      rate (FHR) and the fetal umbilical artery pulsatility index (UPI) after
      performing genetic amniocentesis. This was a prospective study including 431
      consecutive singleton pregnancies between 14 and 18 weeks undergoing genetic
      amniocentesis in our institution. Doppler measurements were obtained
      transabdominally before and immediately after the procedure. Structural
      malformations detected by ultrasound were excluded. Student's t-test was
      performed for comparisons among different groups and observed mean changes. The
      results showed a significant decrease in FHR post-amniocentesis (mean 1.5 beats,
      t = 3.47, P < 0.01) and a non-significant elevation in UPI (mean -0.01, t = 
      0.29, P = 0.77) after the procedure. Differences in FHR could be found when
      analyzed by each gestational week. These preliminary data suggest that although
      acute fetal hemodynamic changes are detected after genetic amniocentesis, such
      changes are unlikely to have clinical relevance. However, it is reasonable to
      propose the use of Doppler as a method of assessing hemodynamic effects caused by
      prenatal invasive procedures in order to provide more accurate in vivo research
      on this issue.

PMID- 8745423
TI  - Newborns' sleep-wake patterns: the role of maternal, delivery and infant factors.
AB  - OBJECTIVE: The purpose of this study was to assess the sleep-wake patterns of
      fullterm (> or = 37 weeks) newborns and to evaluate the effects of specific
      factors including maternal gestational diabetes, infant size and anthropometric
      measures, gender, gestational age and delivery variables. METHODS: Two-hundred
      twenty newborns were studied in the hospital nursery for a continuous 24-h period
      with miniature activity monitors attached to the infants' ankles. The sample
      consisted of 102 infants of gestational diabetic mothers (IGDM) and 118 controls.
      Anthropometric measurements were obtained and maternal and infant characteristics
      were recorded. RESULTS: The newborns had a discernible diurnal sleep pattern and
      slept twice as much during the nighttime as daytime hours (P < 0.001). Higher
      skinfold measurements correlated significantly with increased quiet and
      motionless sleep (P < 0.05) for the IGDM but not for controls. Sleep of infants
      born at later gestational ages was characterized by increased percent of quiet
      and motionless sleep (P < 0.0001). No direct gender effects were identified.
      CONCLUSIONS: Multiple factors were associated with the sleep-wake patterns of the
      newborns on our study cohort including maternal glucose values during pregnancy,
      increased measures of adiposity in IGDM, increased gestational age, mode of
      delivery and delivery Sequence. Investigation of the sleep-wake characteristics
      of neonates using activity monitors is a noninvasive method for gaining new
      understanding of the relationships between sleep wake activity patterns and
      infant characteristics.

PMID- 8745424
TI  - Diurnal non-stress test variations in healthy term fetuses. A call for evening
      appointments for fetal testing.
AB  - OBJECTIVE: The null hypothesis is that the time of day during which non-stress
      testing is performed does not influence the reactivity of the test. STUDY DESIGN:
      Fetal heart rate (FHR) monitoring was performed in 65 healthy term fetuses at
      09:00, 14:00 and 21:00 h, in a quiet room exposed to daylight 2 h after maternal
      meals. Each session lasted 20 min. Smoking mothers were excluded. Statistical
      analysis was performed using a double-tailed t-test. RESULTS: Diurnal non-stress
      test (NST) variations exist and are manifested by a higher incidence of a
      reactive NST at 21:00 h compared to a 09:00 h assessment, and an increased number
      and longer duration of accelerations during a 20-min observation period at 21:00
      h compared to a 09:00 h assessment. CONCLUSIONS: Evening appointments for fetal
      assessments may eliminate the need for additional tests due to the decreased
      incidence of nonreactive NSTs. These in turn will decrease both maternal anxiety
      and the expense of further testing.

PMID- 8745425
TI  - Feasibility of neonatal lung imaging using electrical impedance tomography.
AB  - The feasibility of detecting the lungs in preterm babies using electrical
      impedance tomography (EIT) was investigated. A single frequency instrument using
      16 electrodes to apply current and detect peripheral voltages was constructed.
      The instrument applied AC current of 1.5 mA peak-peak at a carrier frequency of
      20 kHz. Images were reconstructed using a sensitivity-regions backprojection
      method. A 9-day-old preterm baby was tested and data were collected at a speed of
      10 frames/s. A dynamic image showing the lungs at full inspiration referenced to
      expiration is illustrated in this paper. Impedance measurements taken across the
      chest during the first 2 s did not show a clear pattern thus demonstrating
      irregular breathing. Region of interest analysis were carried out on the
      reconstructed images and tracked with time. Fourier transforms were then
      performed on these signals and a fundamental frequency at 1 Hz, corresponding to
      normal breathing rate of 60 breaths/min, was detected. Harmonics of the signal
      caused distortion especially on the left lung where the effects of cardiac events
      were more dominant.

PMID- 8745426
TI  - Development of fetal movement--fetal heart rate coupling from 20 weeks through
      term.
AB  - This study documents the development of fetal heart rate (FHR) change in response
      to fetal movement (FM) in healthy fetuses from 20 weeks' gestational age through
      term. Thirty-one fetuses received 50 min of Doppler-based monitoring at 20, 24,
      28, 32, 36 and 38-39 weeks. FHR and FM were continuously digitized. A coupling
      index was computed as the percentage of FMs associated with increases in FHR of 5
      beats/min or more within -5 or +15 s of movement onset. The latency between FM
      onset and FHR change was also computed, as were the amplitude and duration of all
      movements. FM and FHR became more integrated with advancing gestation. Coupling
      increased and the latency between FM and FHR changes decreased. Maternal age,
      blood pressure and fetal sex did not affect FM-FHR coupling, but fetuses of women
      who reported greater stress in their daily lives and had faster heart rates
      displayed reduced coupling. These data suggest that the development of FM-FHR
      coupling reflects the development of the central nervous system during gestation,
      and that development may be affected by maternal factors.

PMID- 8745427
TI  - The sickle haplotypes in Guadeloupe and the African gene flow.

PMID- 8745428
TI  - Modulation of the phenotypic diversity of sickle cell anemia.
AB  - Sickle cell anemia is noted for being phenotypically heterogeneous. This suggests
      that there are genetic influences that moderate the effects of the sickle
      hemoglobin mutation. In this review I focus on genetically determined modulation
      of hemoglobin concentration and fetal hemoglobin levels. Each of these variables
      has important influences upon sickle hemoglobin polymerization and the resulting
      pathophysiology.

PMID- 8745429
TI  - HB Gouda [alpha 72(EF1)His-->Gln], a new silent alpha chain variant.
AB  - We describe a new alpha chain mutant accidentally found in a diabetic patient.
      The propositus is being treated for diabetes mellitus II with 4% glycated
      hemoglobin (Hb A1C). The variant, named Hb Gouda, is not detectable by starch gel
      electrophoresis but appears as a shoulder before the Hb A fraction during the
      chromatographic separation of Hb A1C. The hematological analysis revealed normal
      parameters with a normal serum iron value. No anomalies were reported in
      connection with Hb Gouda. The tryptic peptide map and sequencing of the alpha T-9
      peptide revealed the substitution of a histidine by a glutamine at position 72.
      By selective amplification and sequencing of both the alpha genes, we have
      assigned the new mutation to the alpha 2 gene. Position 72 of the alpha chain is
      a moderately conserved site located between two non-conserved amino acids. This
      site is not involved in heme, dimer or tetramer contacts, or in Bohr effect or in
      2,3-diphosphoglycerate binding.

PMID- 8745430
TI  - HB Hinwil or beta 38(C4)Thr-->Asn: a new beta chain variant detected in a Swiss
      family.
AB  - This paper reports a new hemoglobin variant which was identified while
      investigating the cause of a mild erythrocytosis. The abnormal beta-globin chain
      was detected by reversed phase chromatography. Mutation mapping of the beta
      globin gene by polymerase chain reaction and denaturing gradient gel
      electrophoresis followed by sequence analysis revealed a C-->A transversion at
      codon 38, predicting a Thr-->Asn substitution. Tryptic peptide mapping by liquid
      chromatography electrospray mass spectrometry, followed by conventional Edman
      peptide sequence analysis, confirmed the predicted amino acid substitution. In
      contrast to the only other known mutation at codon 38, Hb Hazebrouck (Thr-->Pro),
      this hemoglobin is stable and shows elevated oxygen affinity.

PMID- 8745431
TI  - The importance of the 3' untranslated region for the expression of the alpha
      globin genes.
AB  - With a reverse transcription-polymerase chain reaction procedure, we have
      determined the relative quantities of alpha 2- and alpha 1-mRNA in several
      patients with heterozygosities for alpha 2- or alpha 1-globin gene mutations, in
      subjects with two forms of alpha-thalassemia-2 (-3.7 kb; -4.2 kb), and in two
      children with an alpha-globin gene triplication. Mutations in either one of the
      two genes do not affect the mRNA production, and the alpha 2- to alpha 1-mRNA
      ratios in our heterozygotes are the same (approximately 2.7) as in normal persons
      with four alpha-globin genes, while the alpha/alpha X ratios of approximately 1.7
      for alpha 2 variants and of approximately 6.2 for alpha 1 variants agree with the
      theoretic values. The deletion of 3.7 kb (leading to the formation of the alpha 2
      alpha 1 hybrid gene) and of 4.2 kb (resulting in the presence of only the alpha 1
      gene) causes the alpha 2/alpha 1 ratio to decrease to approximately 1.7,
      indicating that both are expressed as an alpha 1 gene. Data obtained for an Hb G
      Philadelphia heterozygote (alpha alpha/-alpha G) show that the alpha 2 alpha 1
      hybrid gene produces approximately 30% less mRNA than an alpha 1-globin gene on a
      normal chromosome, which may be caused by loss of some sequences 3' to the alpha
      2 gene. The same may be the case for the alpha 1-globin gene on the chromosome
      with the 4.2 kb alpha-thal-2 deletion. These results suggest an important role
      for sequences located 3' to the terminating codon in regulating transcription.
      Support for this hypothesis was obtained from data for the two children with an
      alpha-globin gene triplication; the high alpha 2/alpha 1-mRNA ratio can be
      explained by assuming that the alpha 1 alpha 2 hybrid gene of the alpha 2(alpha 1
      alpha 2)alpha 1 triplication expresses as an alpha 2 gene.

PMID- 8745432
TI  - The role of proline beta 5(A2) in the functional properties of human adult
      hemoglobin.
AB  - The replacement of beta 5(A2)Pro by Arg in Hb Warwickshire appears to be without
      an effect on the functional properties of human Hb A, despite adding two external
      positive charges close to the central cavity of the hemoglobin tetramer, along
      the dyad axis. To clarify the role of this portion of the molecule involved in
      oxygen-linked anion binding, we have engineered the recombinant hemoglobin alpha
      2 beta (2)5(A2)Pro-->Ala[rHb beta 5(A2)Pro-->Ala]. The rHb beta 5(A2)Pro-->Ala
      exhibits an increased oxygen affinity compared to Hb A, with normal heterotropic
      effects in standard conditions. The increased oxygen affinity may be attributed
      to the absence of proline, which would render the A helix more flexible, thus
      destabilizing the T structure. The normal functional properties of Hb
      Warwickshire may be due to the regulation of oxygen affinity by electrostatic
      effects involving diffusible anions not bound to any specific site.

PMID- 8745433
TI  - beta S haplotypes, alpha-globin gene status, and hematological data of sickle
      cell disease patients in Guadeloupe (F.W.I.).
AB  - The beta gene cluster haplotypes, alpha gene status, Hb F level and hematological
      parameters have been characterized in 154 unrelated Guadeloupe patients with
      sickle cell disease: 112 with sickle cell anemia, 26 with SC disease, 15 with Hb
      S-beta-thalassemia, and one patient with Hb S in association with the hereditary
      persistence of fetal hemoglobin. Fourteen haplotypes in 16 combinations were
      found, the three major African haplotypes were present on 92% of all chromosomes:
      73% Benin, 11% Bantu, 8% Senegal. Among SS patients, 57% were Benin homozygotes,
      one patient was a Senegal homozygote, one patient was a Bantu homozygote, and all
      the others were heterozygous. The A gamma T chain was observed on seven
      chromosomes and about 5% of the analyzed beta S chromosomes exhibited atypical
      haplotypes. The common haplotype beta C was found in all patients with SC
      disease. An interesting feature was the high frequency (44%) of deletional alpha
      thalassemia among SS patients. Two patients have an alpha-gene globin
      triplication. The DNA haplotypes and alpha-gene status have been correlated with
      hematological parameters in these patients. The anthropological aspect of these
      data is interesting as the haplotypes of the beta-globin gene throw light on the
      slave trade from the various parts of Africa to the Caribbean Islands in
      particular, and North America in general.

PMID- 8745435
TI  - Hb J-Baltimore [beta 16(A13)Gly-->Asp] associated with beta(+)-thalassemia in a
      Spanish family.

PMID- 8745434
TI  - HB Swan River [alpha 6(A4)ASP-->Gly] observed in a Japanese man.

PMID- 8745436
TI  - [Smoking and the development of Warthin tumor of the parotid gland].
AB  - The smoking history was surveyed in 128 cases with Warthin tumor of parotid gland
      in order to investigate the relationship between smoking and the development of
      the tumor. Two hundred cases of middle or old age normal persons and 136 cases
      with pleomorphic adenoma in parotid gland served as the controls. The percentage
      of smoker in patients with Warthin tumor (96.9%) was much higher than that of
      middle or old age normal persons (25.5%) and patients with pleomorphic adenoma
      (24.3%). Morever, the amount of smoking was greater and the smoking history was
      longer in patients with Warthin tumor. When the male and female patients were
      analysed respectively, the same results were shown. This case--control study
      suggests that smoking may be one of the etiologic factors associated with the
      development of Warthin tumor.

PMID- 8745437
TI  - [Clinical study of the tongue reconstruction with the free gracilis myocutanious
      flap].
AB  - From May 1988 to December 1991, 9 cases of the tongue defect were reconstructed
      with the free gracilis myocutanious flaps to maintain the tongue motive force.
      The survival rate was 77.8% (7/9). The follow--up period was 18 months to 5
      years. The volume of the flaps didn't obviously atrophy. The shapes of tongue
      reconstructed were chubby. In their function, the electrokinetic appearance was
      detected after post--operation 6 months by point electrode electromyography
      (EMG), and with the time being, the action tended to increase. Compared with the
      free forearm flap, the gracilis myocutanious flap is better in shape and
      function, and with muscle and nerve. Therefore, the functional reconstruction of
      the tongue defect relates not only with neurotropism, but also with the character
      and volume of the flap. It was confirmed by many experiments and clinical studies
      that the muscle transplanted can be under control of the nerve by motor never
      reproducing.

PMID- 8745438
TI  - [Experimental research on porcelain fused to the surface of pure titanium and
      titanium alloys].
AB  - Titanium material has been widely used in prosthodontics since the end of 1980s.
      However, the research on porcelain fused to the surfaces of titanium material was
      quite few. This article introduced the technological process of low-fusing dental
      porcelain--Ceratin fused to pure titanium and titanium alloys. The values of the
      bond strength of Ceratin and titanium substrates were obtained by shearing test
      with INSTRON Model-1185. The average value of the shearing strength between TA2
      and Ceratin was 31. 01MPa. The corresponding value between TC4 and Ceratin was
      33.73MPa. The interface between Ceratin and titanium substrate was observed with
      scanning electron microscope (SEM). The results of this research proposed that it
      is hopeful that Ceratin is used as special procelain with titanium material.

PMID- 8745439
TI  - [Alkaline phosphatase levels in gingival crevicular fluid of periodontitis before
      and after periodontal treatment].
AB  - Gingival crevicular fluid (GCF) samples were collected from 204 teeth from 35
      subjects, including 8 rapidly progressive periodontitis (RPP), 14 chronic adult
      periodontitis (CAP), 7 marginal gingivitis (MG) and 6 healthy subjects (H). The
      results of alkaline phosphatase (ALP) examination indicated that the ALP levels
      from CAP and RPP patients were significantly higher than those from H subjects
      and MG patients. The ALP levels were closely related to the amount of GCF flow
      and various clinical periodontal parameters, especially to probing depth and
      attachment loss. The ALP levels and the various clinical parameters decreased
      significantly after periodontal therapy. The present study suggests that the
      measurement of GCF--ALP could be an useful adjuctive criterion for detection of
      periodontal inflammatory status and extent of tissue destruction.

PMID- 8745440
TI  - [Biomechanical base of partial odontectomy (POT) for advance periodontitis: 3
      dimension finite element stress analysis].

PMID- 8745441
TI  - [Proliferating cell nuclear antigen (PCNA) in oral leukoplakia].

PMID- 8745442
TI  - [Location of Bacteroides gingivalis in periodontal tissues].

PMID- 8745443
TI  - [An electron microscopic histochemical study on proteoglycans in salivary gland
      myoepithelioma].
AB  - Four myoepitheliomas and four parotid gland were studied histochemically be
      electron microscopy after stain with ruthenium red. It was found that the normal
      myoepithelial cells of parotid gland had no secretion function, whereas the
      myoepithelioma cells were capable of secreting proteoglycans and might form the
      myxoid region in this tumor. The authors propose that in the pathological
      diagnosis and differentiat diagnosis of salivary gland epithelial tumors, the
      appearance of the myxoid region is not only the pathological feature of
      pleomorphic adenoma, but also the pathological change of myoepithelioma.

PMID- 8745444
TI  - [Bone density of human condyle].

PMID- 8745445
TI  - [Evaluation of the long-term curative effect of pulp mummification].
AB  - Fifty--three teeth with pulpitis treated by pulp mummification and followed--up
      for fifteen years were examined. Of them, excellent result was achieved in 11
      teeth (20.75%), good in 8 teeth (15.10%) and failure in 34 teeth (64.15%).
      Radiologically, 8 good cases were characterized by badly delineated periodontal
      ligament, increased periodontal ligament space in width, indistinct lamina dura
      and/or local increase in the density of bone; 34 failure cases were characterized
      by the radiolucent area or small lesion around apex with clear radiopaque line on
      the circumference of the area or local increase in the density of bone. These
      radiographs showed that chronic inflammations existed in periapex. Although
      further investigations are needed to identify the reasons leading to chronic
      inflammations, the results should be considered seriously when pulp mummification
      is upon selection.

PMID- 8745446
TI  - [In vitro study on synthetic "CaF2-like" material: preparation and
      characterization].

PMID- 8745447
TI  - [Quantitative analysis of oncogene ras P21 expression in oral precancerous lesion
      and squamous cell carcinoma].

PMID- 8745448
TI  - [Clinical and experimental studies on the use of hard-polymerized resin veneer].

PMID- 8745449
TI  - [The effect of topically garlic solution painting on experimental oral precancer
      and oral cancer in rats].

PMID- 8745450
TI  - [Evaluation of the condylar position in the diagnosis of temporomandibular joint
      dysfunction syndrome].
AB  - 26 cases with Temporomandibular Joint Dysfunction Syndrome (TMJDS) were included
      in the present study. Fully corrected lateral tomogrames of TMJ in the
      intercuspid position were taken for all the cases; and fully corrected lateral
      arthrotomogrames were taken for 19 cases (21 joints) of them. The area and linear
      measurements of the joint space were made with the aid of computer. The results
      showed that the position of the condyle in the patients with TMJDS was located in
      the posterior position of the fossa. Statistics results showed that there was
      significant difference between the patient group and control group. Although the
      posterior displacement of the condyle was often associated with the anterior
      displacement of the disc, it was not always agreement with the anterior disc
      displacement. So, the exact diagnosis of disc displacement should be still on the
      basis of arthrography or other examinations, such as CT or MRI.

PMID- 8745451
TI  - [Macroscopic and pathologic observations of the cadaver's temporomandibular
      joints with or without internal derangement].

PMID- 8745452
TI  - [Interleukin-6 activity in synovial fluids of temporomandibular joint distrubance
      syndrome].
AB  - Using the IL-6-dependent mouse hybridoma cell line KD 83, IL-6 biological
      activity in synovial fluids of the patients with Temporomandibular Joint
      Disturbance Syndrome (TMJDS) was tested. The results show that IL-6 level is high
      in 13 cases of 18 patients with TMJ degenerative changes and 5 cases of 12
      patients with TMJ Disc Displacement. IL-6 level is less than 100 U/ml in all
      patients with Masticatory Muscle Disorder (59.4 +/- 29.4 U/ml). In addition, it
      has been found that TMJDS tends to have acute and chronic stages and IL-6 is
      probably related to acute stage of the patients.

PMID- 8745453
TI  - [Barrier membrane technique in oral medicine].

PMID- 8745454
TI  - [In vivo tissue distribution of laryngeal cancer drained lymph node lymphocytes
      in tumor-bearing mice].
AB  - The distribution of 3H-TdR labeled human laryngeal cancer drained lymph node
      lymphocytes (LNL) to human laryngeal squamous cell carcinoma were traced in PHC3
      bearing nude mice, and the radioactivity in tissues was detected. 30.7% labeled
      cells were localized in live in first day after transfer, and a few in lung,
      spleen and kidney. Labeled cells were reduced weekly and by the end of the fourth
      week there were still 4.3% in live, but very few were detected in the tumor site.
      This indicated that cancer drained LNL had no specificity to tumor, and could not
      infiltrate into tumor sites. So besides directly attacking tumor cells in vivo,
      possibly, there are some indirect mechanisms to mediate tumor regression.

PMID- 8745455
TI  - [A preliminary evaluation of the horizontal-vertical hemilaryngectomy in 41
      cases].
AB  - 41 patients (23 men and 18 women) with squamous cell carcinoma of the larynx were
      treated with horizontal-vertical hemilaryngectomy from December 1979 to June
      1989. The patient's age ranged from 35 to 64 years. There were 37 cases (90.2%)
      in the stage III and IV. All the patients had acquired the function of speech in
      different quality, and good swallowing. 80.5% (33 cases) of them were extubated.
      The 5-year survival rate was 70.7%. In this article, the main procedure of the
      operation and preventive method of the aspiration were described, and the failing
      factors of the treatment were discussed.

PMID- 8745456
TI  - [Pre-operative radiotherapy for N0 supraglottic carcinoma: a randomized study].
AB  - A randomized study on 100 patients of N0 supraglottic squamous cell carcinoma
      with at least 3 years of follow-up was performed. Surgery alone was used in 56
      patients, and combined therapy in 46 patients. The neck failure occurred in 14
      (26%) patients and 7 (15%) patients respectively, there was no statistically
      difference (P = 0.287). Neck failure was higher in T4 stage supraglottic
      carcinoma for controlling of regional recurrence.

PMID- 8745457
TI  - [Expression of proliferating cell nuclear antigen (PCNA) in premalignant lesions
      of laryngeal epithelium].
AB  - It is important to study the proliferative activity of cells in the premalignant
      lesions of laryngeal epithelium. Using PC-10, an antibody to PCNA and a standard
      immunohistochemical staining, we examined 11 cases of simple hyperplasia of
      epithelium (SHE), 32 cases of atypical hyperplasia of epithelium (AHE) and 42
      cases of laryngeal squamous cell carcinoma (LSCC) for expression of PCNA, a
      protein associated with DNA polymerase delta and DNA replication. The results
      revealed that the PCNA indices in SHE, AHE and LSCC were 9.57%, 27.33% and
      68.05%, respectively. The PCNA indices were 13.79%, 30.84% and 39.94%, in the
      mild, moderate and severe AHE, respectively. There were significant differences
      among the SHE, AHE and LSCC. A good correlation was found among different degrees
      of AHE. The pattern and location of PCNA positive cells in the intraepithelium
      had diagnostic importance. PCNA might provide a useful tool for studying cell
      proliferation in situ under normal and pathological conditions.

PMID- 8745458
TI  - [The relationship between the phenotype of tumor infiltrating cells and the
      prognosis in laryngeal cancer].
AB  - By using the method of immunohistochemical avidin-biotin-peroxidase complex
      (ABC), toluidine blue and HE staining, the infiltrated grade and dispersed
      feature about the T-lymphocytes, B-Lymphocytes, macrophages, langerhans cells,
      mast cells and eosinophils of peritumoral stroma were investigated in 82 cases
      with laryngeal carcinoma. A stepwise logistic regression analysis of eight
      clinicopathologic variables and the density of six kinds of tumor infiltrating
      cells in the study were analyzed with the clinical outcome of the patients. The
      results showed that T-lymphocytes was the major infiltrated cells. The other
      cells such as macrophages, langerhans cells, mast cells and eosinophils were also
      to be found in local infiltration, but the B-cell was scanty. All these cells
      except B-cell had significant effect on the 5-year survival rate of the patients.
      By the multivariate analysis, the peritumoral infiltrated eosinophils was the
      most influential variable affecting clinical outcome, followed by the peritumoral
      infiltrated T-lymphocytes and the tumor histologic grade. We concluded that tumor
      infiltrating cells played a critical role in local host antitumor immune
      reaction.

PMID- 8745459
TI  - [The value of polymerase chain reaction on Epstein-Barr virus subtypes in the
      differentiation of benign and malignant nasopharyngeal biopsies].
AB  - Polymerase chain reaction (PCR) of Epstein-Barr virus (EBV) EBNA-2 type A (PCR-A)
      along with dot blot hybridization using EBV DNA Bam-W and EBNA-2 type A and B
      fragment as the probes (DBH-W, -A, and -B) was performed in the nasopharyngeal
      biopsies. The positive rates of PCR-A, DBH-W, -A and -B were 83.9%, 80.6%, 74.2%
      and 0.0% in 31 cases of nasopharyngeal, respectively, and 12.0%, 40.0%, 92.0% and
      0.0% in 25 cases of chronic nasopharyngitis (NP), respectively. There were
      significant differences between NPC and NP or non-NPC (P < = 0.0001) detected by
      PCR-A. The results indicated that positive PCR-A would be valuable for early
      diagnosis of nasopharyngeal carcinoma. The reasons which might make those
      differences were discussed.

PMID- 8745461
TI  - [The morphologic changes of outer hair cells induced by hypotonic, hypertonic
      medium and electromotility].
AB  - For further understanding of biological features of cochlear outer hair cells,
      outer hair cells were isolated from guinea pig cochlea with micromechanical
      method and observed when the microosmotic concentration of their culture medium
      were changed. Outer hair cells shortened 3.14 +/- 0.76% (P < 0.01) within one
      minute after the osmotic concentration of the medium decreased to 280 mmol/L,
      accompanied with increase of cell diameter. Elongation of 3.34 +/- 1.09% (P <
      0.05) of outer hair cells were observed after osmotic concentration of the medium
      was increased to 320 Os mmol/L, accompanied with decrease of cell diameter.
      Oscillatory elongation and shortening of outer hair cells and oscillatory
      displacements of intracellular organelles could be observed when square wave
      electrical potentials were applied across isolated outer hair cells. Hypertonic
      high potassium medium (K+ 100 mmol/L, 320 Osmmol/L) decreased the oscillatory
      movement of the cells by about 43.14% (negative potential) and 46.17% (positive
      potential) (P < 0.05). The shape of outer hair cells restored when the medium was
      isotonic. The mechanism and biological bases of outer hair cell movement were
      discussed.

PMID- 8745460
TI  - [A prospective study on relationship between abnormal nasopharyngeal mucosa and
      nasopharyngeal carcinoma].
AB  - Abnormal nasopharyngeal mucosa was defined as abnormal finding under the
      examination of nasopharyngoscope. 43541 healthy persons aged 30-64 were observed
      for 6 years in the high risk area of NPC, by mean of EBV serological and
      nasopharyngeal cavity examination. The results are as follows. 1. In the high
      risk area of NPC, abnormal nasopharyngeal mucosa such as follicle hyperplasia and
      bulge are common in the younger people, especially in the post-roof of the
      nasopharyngeal cavity. 2. There was no significant difference on statistics
      between the abnormal and normal groups on the positive rate and GMT of EBV
      VCA/IgA. Abnormal nasopharyngeal mucosa did not change with the change of VCA/IgA
      titer. 3. There was significant difference on the prevalence rate of NPC between
      the abnormal nasopharyngeal mucosa and normal groups except the age, sex factors.
      There was no confirmation of the abnormal nasopharyngeal mucosa as precancerous
      lesion.

PMID- 8745462
TI  - [Ultracytochemical observation of secretory cells and surfactant-like lamellar
      bodies in mucosa of eustachian tube].
AB  - The distribution of secretory cells and surfactant-like lamellar bodies in mucosa
      of the guinea pig eustachian tube were studied ultracytochemically. Classified by
      means of their morphologic characteristics, three types of secretory cells were
      identified. The dark granulated cells were predominant in the tympanic orifice,
      the mixed cells were predominant in the isthmus portion, while the light cells
      were predominant in the pharyngeal orifice. The distribution of the secretory
      cells in different part of the eustachian tube might play a role in the
      pathogenesis of middle ear effusions. Surfactant-like lamellar bodies were found
      in ciliated cells, nonciliated cells and secretory cells of the eustachian tube
      mucosa. Surfactant-like lamellar bodies (surfactant-like substance) are important
      in maintaining the physiological function of the eustachian tube, their behavior
      in normal and pathological states should be further studied.

PMID- 8745463
TI  - [Alternation of intracellular Ca2+ caused by streptomycin in the isolated
      cochlear OHC].
AB  - Stained with fluorescence, the intracellular free calcium concentration (Ca2+) of
      the cochlear out hair cell (OHC) isolated from guinea pigs was measured using
      ACAS 570. Streptomycin caused a remarkable rise in Ca2+ and reached peak value in
      60s, decreased gradually after lasting for 60s in that value. The Ca2+ fell back
      to primary level in another 100s and followed by a slight drop. The distribution
      of free calcium in the OHC was showed. The rise of intracellular free calcium in
      the OHC was assumed to be a period in the ototoxicity caused by aminoglycoside
      antibiotics.

PMID- 8745464
TI  - [Observation of cristae of posterior ampullae with laser Doppler].
AB  - To set up the methodology of measuring vestibular blood flow was the key to the
      study of vestibular microcirculation. 10 guinea pigs' posterior ampullae cristae
      blood flow were measured with Laser Doppler Flowmetry. RESULTS: cochlear flow was
      318.39 +/- 91.66mV. Cristae of posterior ampullae was 194.00 +/- 45.26mV. The
      arterial blood pressure was stable in 9.99 approximately 10.27kPa. The present
      results showed cochlear and vestibular blood flow were 62.14% and 37.86% in total
      inner ear blood circulation. The latter appeared to be about one half of cochlear
      blood flow. These suggested that the blood flow of posterior ampullae can reflect
      the blood flow of vestibular to some degree. Laser Doppler was technically
      simple, non-invasive, highly stable, reproducible and sensitive.

PMID- 8745465
TI  - [The olfactory neurotoxicity of cisplatin and effects of two drugs].
AB  - 32 guinea pigs were used as animal models for the study of cisplatin induced
      olfactory neurotoxicity and the effects of sodium thiosulfate (STS) and cystine
      on the toxicity by light and electron microscopy. The results revealed that the
      olfactory epithelium, olfactory nerve and the olfactory bulb were all damaged by
      the application of cisplatin and manifested as the lysis of the myelinated nerve
      fibers of olfactory epithelium, edema and degeneration of the axons, atrophy of
      the olfactory epithelium and the compensatory proliferation of Bowman's glands.
      STS and cystine did not show significant effects on the neurotoxicity of
      cisplatin. The data suggested that cisplatin is an important toxic drug for
      olfactory system.

PMID- 8745466
TI  - [Western blot analysis of serum autoantibodies against inner ear antigens in
      patients with systemic lupus erythematosus].
AB  - The purpose of this study was to identify the cross-reacting autoantibodies
      against inner ear antigens in patients with systemic lupus erythematosus (SLE).
      Inner ear antigens of guinea pigs were prepared. The sera from 18 patients with
      SLE without hearing loss and 11 normal subjects were analysed by immunoblotting
      assay. The results showed that 16 patients with SLE had cross-reacting
      autoantibodies, while 11 normal objects were all negative (P < 0.01), these
      suggested that the inner ear may be one of the targets involved by SLE. To
      further investigate the correlation between hearing status of SLE and
      autoantibodies against inner ear antigens will be of great value to explore the
      pathogenesis of inner ear insults resulted from certain systemic autoimmune
      diseases.

PMID- 8745467
TI  - [Acoustic characteristics of external auditory meatus after tympanoplasty with
      open mastoid reconstruction].
AB  - This study investigated the effects of down-wall tympanoplasty (open technique
      included skeletonizing of mastoid) upon external auditory meatus resonance
      characteristics. The probe tube microphone measurement was performed twice pre
      and post operatively. The resonance frequency of external auditory meatus
      remained constant, but the peak amplitude was increased by 0.83dB SPL (P < 0.05).
      The results indicated that a tympanoplasty with standard open techniques did not
      affect the normal external auditory meatus resonance characteristics.

PMID- 8745468
TI  - [Removal of petrous bone cholesteatoma and obliteration with adipose tissue].
AB  - Three cases of petrous bone cholesteatoma removed through translabyrinthine
      cochlear approach with the surgical defect obliterated by using adipose tissue
      covered with superficial temporalis fasia flap were reported. The average follow
      up period was two years without any sign of recurrence. The etiology, diagnosis
      and methods of surgical treatment were discussed.

PMID- 8745469
TI  - [Malignant melanoma of nasal cavity: report of 24 cases].
AB  - The malignant melanoma of nasal cavity is one of the refractory diseases. The
      malignant degree and the recurrent rate of this disease are high. And it is very
      easy to make misdiagnosis. This article reviewed the clinical and pathological
      data of malignant melanoma of nasal cavity for 20 years from 1971 to 1991. All
      the patients were followed up. We found that there were altogether 24 cases of
      this disease which covered 0.02% of all the inpatients during that period of
      time. The pathological characteristics of this tumor showed that there was a
      typical fore-melanin body in different tumor cells. If we pay attention to the
      minor and grained melanin, misdiagnosis can be avoided. Surgery is the first
      choice for this disease. And the post-operative radiotherapy, laser therapy gives
      a better result.

PMID- 8745470
TI  - [Current status and prospects in pediatric pathology].

PMID- 8745471
TI  - [Analysis of 145 hepatic disorders from autopsy cases of children].
AB  - A statistical analysis was made on 145 cases of hepatic disorders from 2659
      autopsies in children. The results showed that hepatic disorders accounted for
      5.5% (ranking fourth) of the various systemic disorders. Viral hepatitis was the
      most common entity (55.2%) with cirrhosis following (20.7%). Most of the hepatic
      disorders occurred under 1 year of age, accounting for 70.34% of total. The
      annual detection rate of viral hepatitis showed an increasing trend,
      demonstrating that hepatic disorders, especially viral hepatitis, are the major
      diseases that threaten the life of children.

PMID- 8745472
TI  - [Analysis of 110 cases of sacrococcygeal lesions in children].
AB  - 110 cases of sacrococcygeal lesions seen in the Guangzhou Children's hospital
      were reviewed. 42 cases were anomalies, 66 cases were tumors and 2 were
      inflammatory granulomas. As compared to data in western literatures, the
      morbidity of anomalies in this series was lower than that of tumors, whereas in
      western reports the morbidity of anomalies was much higher than that of tumors.
      Another interesting point was that the morbidity of meningocele (MC) in this
      series was much higher than that of myelomeningocele (MMC) of spina bifida (7:1).
      According to a study in Australia, the MC:MMC was 1:5. We suggest that endodermal
      sinus tumor should be considered as an independent entity of there was no other
      tissue component (organlike component) found in tumor section. We also suggest
      that if neuroblastoma and/or other immature neuroectodermal component is observed
      in a teratoma, it should be classified as malignant rather than benign.

PMID- 8745473
TI  - [Study of DNA content, immunophenotype in childhood non-Hodgkin's lymphomas].
AB  - The DNA content, immunophenotypes and Ag-NOR of 63 cases of childhood NHL have
      been studied with flow cytometry and immunohistochemistry. The results showed
      that the incidence of aneuploidy, the numbers of Ag-NOR and PI increased
      significantly with increasing histological grade. The numbers of PI were also a
      valuable prognostic parameter. There was a positive correlation between the
      numbers of PI and AgNOR. No significant correlation was seen between the survival
      rates of diploid and aneuploid tumors. The highest to lowest survival rates being
      in the sequence of unclassified tumors, T-cell tumors and B-cell tumors.

PMID- 8745474
TI  - [A pathological comparison between Hirschsprung's enterocolitis and neonate
      necrotizing enterocolitis].
AB  - Autopsy records of 9 cases of neonate Hirschsprung's enterocolitis (HD) and 16
      cases of neonate necrotizing enterocolitis (NEC) were analysed. It was found that
      the NEC lesions were more extensive than HD lesions, the bleeding and
      inflammation in NEC were also more serious than in HD. From our 21 animal
      experiments in which we tried to clarify the pathogenesis of Hirschsprung's
      enterocolitis and NEC, our preliminary hypothesis fro the development of
      Hirschsprung's enterocolitis being: the distal segment was first obstructed,
      causing the proximal segment to expand, the increase of pressure within the bowel
      resulted in ischemia of the intestines, increased bacterial multiplication in the
      retained feces and bacterial infiltration of the intestinal mucosa. The above
      being the major cause of HD. When the neonate is in asphyxia or shock, ischemia
      of the intestines and immunoallergic reactions occur, due to the lack of IgA in
      the mucosa, the multiplication and infiltration of pathogenic enterobacteria in
      the intestinal wall results in NEC.

PMID- 8745475
TI  - [Reversal of malignant cell phenotype of human pancreatic adenocarcinoma cell
      line by recombinant retroviral vector expressing antisense Ki-ras].
AB  - A recombinant retroviral vector expressing antisense Ki-ras was constructed. The
      recombinant virus DNA was packaged with packaging cell line PA317 cells by the
      calcium phosphate coprecipitation method. The virus supernatant was used to
      infect human pancreatic carcinoma cell line PC-2. After selection with Puromycin,
      resistant colonies were obtained. Stable expressions of retrovirus in both PA317
      and PC-2 cells were exhibited by Northern blot hybridization. A down regulation
      of endogenous Ki-ras was found in PC-2 cells infected with antisense Ki-ras
      construct. It was demonstrated that the antisense Ki-ras did inhibit the cell
      growth rate and 3H-TdR incorporation rate of PC-2 cells. The ability of colony
      formation in soft agar and tumorogenicity in nude mice of PC-2 cells were
      significantly suppressed by the antisense Ki-ras. The results implicate that
      recombinant retroviral vector containing antisense Ki-ras could inhibit target
      gene expression and partly reverse malignant phenotype of pancreatic
      adenocarcinoma cells.

PMID- 8745476
TI  - [Pathologic observations of hepatitis C].
AB  - The morphological changes in liver biopsies from 70 patients with a clinical
      diagnosis of hepatitis C were studied. Sixty-two of the patients had history of
      blood transfusions. All patients were seropositive for anti-HCV by first and
      second generation test and/or were seropositive for HCV RNA by PCR method.
      Clinically, twenty cases diagnosed as acute hepatitis, fifty were chronic
      including 7 cases with both HBV and HCV infection. The main morphological changes
      in acute cases being 1. Focal degeneration of liver cells, including large and
      small droplet fatty changes. 2. Focal necrosis and acidophilic bodies usually
      being surrounded by T lymphocytes. 3. Sinusoidal inflammatory cell infiltration.
      4. Lymphoid aggregation with bile duct epithelial damage was found in 60% of
      portal tracts. The chronic cases included 17 chronic persistent hepatitis cases
      (CPH) and 33 chronic active hepatitis cases (CAH). The main histopathologic
      changes in CAH included dense clusters of lymphocytes (lymphoid aggregates)
      present in the enlarged portal tracts with bridging necrosis and fibrosis,
      lobular inflammation including acidophilic bodies, focal necrosis and fatty
      degeneration. The sinusoidal cells were often hyperplastic. These changes may
      provide useful diagnostic clues for hepatitis C.

PMID- 8745477
TI  - [A study on the appearance of hepatitis B virus markers in renal tissue of
      glomerulonephritis].
AB  - HBV antigens (HBcAg, HBsAg and HBeAg) in 246 cases of renal biopsy specimens with
      various types of glomerulonephritis were examined by immunohistochemical
      techniques. Southern blot hybridization was used to detect HBV DNA in 18 cases.
      The results showed that HBV antigens were frequently found in the tubular cells
      in addition to the appearance of HBV antigens on the glomeruli of certain
      glomerulonephritis. The positive rte of HBcAg in the tubular cells was 21.54%,
      which is higher than that of glomeruli (10.98%). Renal HBV DNA was positive in 15
      cases and among them HBcAg expression in renal tissue in 14 cases and HBV
      antigenemia in 12 cases. The results suggest that HBV may also be implicated in
      the pathogenesis of certain cases of glomerulonephritis and the appearance of HBV
      antigen antibody immunocomplex in renal tissue, aside from originating in the
      circulation, there is the possibility of it originating from renal cells in situ.

PMID- 8745478
TI  - [Primary lymphomas of bone: a clinicopathologic study of 22 cases].
AB  - 22 cases of primary lymphoma of bone (PLB) were reported. Multiple bone
      involvement in two patients, singular bone in twenty patients. One case had
      regional lymph node involvement. Radiological examination revealed 91% had
      diffuse lytic lesions. Histological typing was performed according to working
      formulation. 15 formalin fixed paraffin embedded PLB specimens were studied
      immunohistochemically by use of the avidin-biotin-peroxide complex (ABC) method
      to label monoclonal antibodies. RESULTS: Ten neoplasms were B-cell type, there
      were T-cell type, the two remaining cases did not express. The ratio of primary
      lymphomas in this study in extranodal lymphomas is three times that reported in
      Japan and also higher than that reported in north America in recent years. The
      proportion of T-cell type is also higher than that reported in Japan.
      Differential diagnosis and several factors which influence immunostaining were
      also discussed.

PMID- 8745480
TI  - [Effects of hypoxia on the phenotype of porcine pulmonary arterial smooth muscle
      cells in vitro].
AB  - The effects of hypoxia on phenotype modulation of pulmonary artery smooth muscle
      cells (PASMC) was observed using cell culture and morphometry analysis. The
      results showed that the number of diploid cells and alpha-sm-actin of the hypoxic
      endothelial cell condition medium group (HECCM) was lower and the myofibrils were
      even less than that of the normal endothelial cell condition medium group
      (NECCM). On the contrary, the volume density of rough endothelial reticulum (RER)
      and mitochondria of the HECCM group were higher than that of the NECCM group.
      However, under hypoxic condition for 24 hours, the phenotype of cultured PASMCs
      remained unchanged. It suggests that the HECCM can induce phenotype modulation of
      PASMCs, may be mediated by the pulmonary artery endothelial cells (PAECs) which
      can secrete some cytokines affecting the PASMCs.

PMID- 8745479
TI  - [Detection of CgA mRNA in neuroendocrine cells in gastric carcinoma by in situ
      hybridization].
AB  - Fresh gastric carcinoma specimens from 17 cases were collected. The
      neuroendocrine (NE) cells in gastric carcinoma (GC) and gastric mucosa adjacent
      to the carcinoma (GMAC) were observed using in situ hybridization of chromogranin
      A (CgA) oligonucleotide probe and compared with immunohistochemistry of CgA
      antibody. 5 of the 17 cases of GC showed CgA mRNA positive expression and 7 of
      the 17 cases expressed CgA protein positively. The simultaneous expression of
      mRNA and protein of CgA was present in 4 cases. The NE cells in GC not only can
      store and secrete CgA protein products but also possess the ability to synthesize
      NE products from gene expression.

PMID- 8745481
TI  - [In situ expression of c-myc, N-ras during diethylnitrosamine induced
      hepatocarcinogenesis].
AB  - In order to investigate the action of oncogenes in experimental
      hepatocarcinogenesis, the expression of c-myc, N-ras and H-ras were studied
      during early and late stages of DENA induced hepatocarcinogenesis in rats by
      using in situ hybridization. The results showed that overexpression of c-myc and
      N-ras was presented in teh proliferation hepatocytes and alternated hepatocytes
      foci during the early stage of hepatocarcinogenase, and with the formation and
      progression of hyperplastic hepatocytic nodules, the overexpresion cells of both
      were increased and often accompanied each other. Overexpression of H-ras appeared
      in the middle stage of hepatocarcinogenesis. The data obtained indicate that the
      abnormal expression of N-ras and c-myc in the hepatocarcinogenesis is not only an
      earlier molecule event which may relate to the initiation of HCC, but also the
      molecular basis for the morphogenesis of HCC, and these two functions took
      synergically. However, the abnormal expression of H-ras may have a promotive
      effect on the development of preneoplastic lesions, and also suggests that the
      malignant transformation of hepatocyte needs the cooperation of multiple
      oncogenes.

PMID- 8745482
TI  - [Detection of estrogen receptor messenger ribonucleic acid in normal and
      ovariectomized rat bone].
AB  - Using ovariectomized female SD rats (OVX) as animal osteoporosis models, RNA
      samples were extracted directly from rat bone. Reverse transcriptase-polymerase
      chain reaction (RT-PCR) was used to examine the estrogen receptor (ER) messenger
      RNA (mRNA) level of expression in normal and OVX rat bone tissue. Results
      demonstrated that the rat ER gene is expressed in normal rat bone. DNA sequencing
      showed 300 bases sequence. We found that the OVX rats showed a sharp decrease in
      ER mRNA level when estrogen was reduced after ovariectomy and the expression of
      bone ER mRNA increased during estradiol therapy, suggesting that the expression
      of bone ER mRNA relies upon the level of estrogen. In addition, ER plays a very
      important role in the pathogenesis by means of its gene regulatory functions.

PMID- 8745483
TI  - [The ultrastructure of intermediate type trophoblast cell].
AB  - Transmission electron microscopy was used to clarify the detailed morphology of
      the "intermediate type" trophoblast cell in normal and tumor issue. 67 normal
      placental villi specimen, 10 placental bed specimens and 10 malignant mole, 10
      hydatidiform mole, 5 choriocarcinoma specimen (the last three types taken before
      chemotherapy) were examined. Results showed that the transitional type
      trophoblasts of the placenta were developed from cytotrophoblasts through
      differentiation and fusion to syncytiotrophoblasts which showed features of
      maturation and aging, having features of cytotrophoblast nuclei and
      syncytiotrophoblast cytoplasm. The transitional trophoblast of placental bed
      showed similar morphology as that of transitional type cells of villi. The
      morphology of transitional type cells of villi. The morphology of transitional
      type cells of trophoblastic tumors had both normal morphology and cellular
      hyperplasia, atypia and features of tumor ultrastructure. The prominent feature
      was the high electron density of the granules and polymorphic cysts crowded in
      villi, demonstrating that the morphology of "intermediate type" trophoblasts in
      placental and tumor tissue are similar, whereas heterotype cellular morphology is
      present in varying degrees in tumor tissue.

PMID- 8745484
TI  - [Advances in the pathological study of hepatitis C].

PMID- 8745485
TI  - [Oncogenes in gynecological malignancies].

PMID- 8745486
TI  - [A study on expression of tumor suppressor gene p53 in endometrial carcinoma].
AB  - OBJECTIVE: To observe the relationship between suppressor gene p53 expression and
      endometrial carcinoma. METHODS: Expression of p53 was studied by
      immunohistochemistry in paraffin sections from 23 normal endometrium, 44
      endometrial hyperplasia and 103 endometrial carcinoma. RESULTS:
      Immunohistochemical staining of p53 protein was negative in normal and
      hyperplastic endometrium but positive in 47.6% of endometrial carcinoma. In
      endometrial carcinoma, p53 over expression was significantly associated with
      histologic type, tumor grade, presence of vascular invasion and DNA aneuploidy.
      The survival rate of patients with p53 expression is significantly lower than
      that of patients without p53 expression (P < 0.001), the 5-year survival rate is
      59.9% and 83.4% respectively. Patients with expression of mutant forms of the
      tumor suppressor gene p53 products had a 6.34-fold increased risk of death as
      compared with patients without p53 expression by Cox proportional hazards model.
      CONCLUSIONS: Aberrant expression of p53 gene is indicative of aggressive
      biological behavior and poor survival in endometrial carcinoma.

PMID- 8745487
TI  - [Expression of p53 gene protein in squamous cell carcinoma and precancerous
      lesion of vulva].
AB  - OBJECTIVES: To investigate the relationship between p53 gene protein expression
      and vulvar carcinoma. METHODS: Expression of p53 gene mutative protein was
      determined by immunohistochemical technique in 17 specimens of vulva squamous
      cell carcinoma, 11 of atypical hyperplasia, 22 of lichen sclerosus et atrophicus,
      34 of hyperplastic dystrophy, 48 of mixed dystrophy. Normal skin samples from
      abdomen and legs, and adjacent tissues of vulvar cancer were served as controls.
      RESULTS: All specimens of normal skin showed no p53 gene mutative protein
      expression. However, p53 protein positive rates were 52.9% (9/17) in carcinoma
      group, 54.5% (6/11) in atypical hyperplasia, 13.6% (3/22) in lichen sclerosus et
      atrophicus group, 20.8% (10/48) in mixed dystrophy, 14.7% (5/34) in hyperplastic
      dystrophy. CONCLUSIONS: p53 gene mutative protein had a higher expression rate in
      vulva squamous cell carcinoma and precancerous lesion than that in various types
      of vulva dystrophy (P < 0.01). These data suggested that overexpression of p53
      gene mutative protein may be related to the oncogenesis of vulva malignancy.

PMID- 8745488
TI  - [Human papillomavirus, human cytomegalovirus and p53 gene in cervical carcinoma].
AB  - OBJECTIVE: To investigate the role of human papillomavirus (HPV) human
      cytomegalovirus (HCMV) infections and p53 gene mutations in the oncogenesis of
      cervical cancer and to clarify the association between p53 inactivation and the
      presence of HPV DNA. METHODS: We examined 38 primary cervical carcinomas and 21
      normal cervical specimens for the presence of HPV and HCMV DNA sequences by
      multiple primers PCR and nest primers PCR. The structure of p53 gene (exons 6-8)
      was also analyzed by PCR-SSCP silver staining method. RESULTS: Mutations of p53
      gene (exon 7) were detected in 2 of 38 tumors. One of the cases with p53 mutation
      was positive for HPV 16 and two positive for HCMV. HPV 16 and 18 infections were
      noted in 63.2% (24/38) of the tumors, the positive rate of HCMV was 84.2%
      (32/38). However, HPV 16,18 and HCMV infection occurred in 4.8% and 38.1%
      respectively in 21 normal cervical specimens. 21 of the 24 HPV 16,18 positive
      tumors were also HCMV positive, but none of the normal cervical tissues was
      infected with both HPV and HCMV. CONCLUSION: Detection of p53 mutations in
      cervical carcinoma is infrequent and apparently independent of HPV infection.
      Cervical carcinoma is strongly associated with HPV 16 and 18 infection. A
      synergistic interaction may occur between HPV and HCMV infections in the
      oncogenesis of cervical cancer.

PMID- 8745489
TI  - [Overexpression of C-erbB3 in transitional cell carcinoma of the ovary].
AB  - OBJECTIVE: To determine the prevalence of C-erbB3 abnormal protein expression in
      transitional cell carcinoma of the ovary in our hospital and to analyse the
      correlation between the overexpression of C-erbB3 protein and prognostic
      parameters of transitional cell carcinoma of the ovary. METHODS: Thirty-two
      transitional cell carcinoma of the ovary and 20 normal ovaries were studied for
      overexpression of C-erbB3 protein by immunohistochemical staining (IHS), using
      the monoclonal antibody RJT2 on paraffin sections. RESULTS: Forty seven percent
      of 32 samples of transitional cell carcinoma of the ovary showed positive IHS
      with RJT2, and 39% of 20 normal ovaries showed positive cytoplasmic and membrane
      staining (P > 0.05). C-erbB3 overexpression did not correlate with age, CA125
      levels, histological grade and lymph node metastases, but patients with
      overexpression of C-erbB3 had a poorer prognosis. CONCLUSION: Overexpression of C
      erbB3 is a common event in transitional cell carcinoma of ovary. Further studies
      are warranted to clarify the role of C-erbB3 in transitional cell carcinoma of
      the ovary.

PMID- 8745490
TI  - [The change of filtration-index of erythrocyte malonyldialdehyde and superoxide
      dismutase in patients with pregnancy induced hypertension].
AB  - OBJECTIVE: To observe the relationship between the filtration-index of
      erythrocytes and concentration of erythrocytic superoxide dismutase (SOD), plasma
      malonyldialdehyde (MDA) in cases of pregnancy induced hypertension (PIH).
      METHODS: We have measured the level of MDA and filtration-index, SOD content of
      erythrocytes in maternal and cord blood of 31 cases with PIH (group A) and 25
      cases of normal pregnancy (group B) using TBA method, nucleopore membraned cell
      deformability meter and pyrogallol self-oxidizing method. RESULTS: The mean
      filtration-index level and erythrocytic SOD were significantly higher in group A
      than those of group B (P < 0.01 and P < 0.05). The mean content of plasmatic MDA
      in group A increased markedly (P < 0.01) compared to that of group B. There was
      no difference of these parameters in cord blood between group A and group B.
      CONCLUSION: The decrease of red cell deformability due to the increase of plasma
      MDA level may be the underlying mechanism of PIH.

PMID- 8745491
TI  - [Evaluation and its clinical significance of anti-platelet granule membrane
      protein-140 autoantibodies and anticalmodulin antibody in patients with severe
      pregnancy-induced hypertension].
AB  - OBJECTIVE: To study the effect of immune function of platelet on the pathogenesis
      of severe pregnancy-induced hypertension. METHODS: 46 plasma samples from
      patients with severe pregnancy-induced hypertension (PIH) were evaluated for
      autoantibodies directed against granule membrane protein-140 (GMP-140) and
      anticalmodulin antibody (A-CaM) using ELISA methods. RESULTS: Autoantibodies to
      GMP-140 existed in 13 patients with severe PIH (28.6%), after SDS-page of
      purified GMP-140 immunoblotting showed that 1 out of 8 sera from patients
      presented a staining band with M.W. of 140 kd. 29 plasma samples were found
      autoantibodies to GMP-140, GP IIb/IIIa and GP Ib/IX, simultaneously. It was shown
      that antiGMP-140 activities coexisted with anti-GP IIb/IIIa and/or anti-GPIb/Ix
      in 29 cases (81.8%). The elevated A-CaM was observed in the patients with severe
      PIH reaching to 20.02 +/- 3.74U/L, that was much higher than those from the
      normal (7.53 +/- 2.57U/L, P < 0.05). CONCLUSION: Our study provided the evidence
      for autoantibodies to GMP-140 and A-CaM in some of patients with severe PIH, it
      has certain importance for further study on the pathogenesis of severe PIH.

PMID- 8745492
TI  - [Predictive value of urinary calcium measurement on occurrence of pregnancy
      induced hypertension].
AB  - OBJECTIVE: To study the predictive value of urinary calcium excretion on
      occurrence of pregnancy-induced hypertension (PIH). METHODS: Twenty-four-hour
      urinary calcium excretion, urinary calcium concentration and urinary
      calcium/creatinine (Ca/Cr) ratio were determined in 184 normal pregnant women and
      30 patients with PIH. RESULTS: Twenty-four-hour urinary calcium excretion,
      urinary calcium concentration, and Ca/Cr ratio in PIH group were significantly
      lower than that in normal pregnant group (P < 0.01). 3 mmol/L of urinary calcium
      concentration and 0.04 of Ca/Cr ratio were chosen as predictive thresholds for
      development of PIH, with sensitivity of 76.2%, 81.0% and specificity of 97.5%,
      98.2% respectively. CONCLUSIONS: Low urinary calcium excretion is a valuable
      marker for prediction of PIH.

PMID- 8745493
TI  - [Risk of malignant changes in hydatidiform mole complicated with pregnancy
      induced hypertension].
AB  - OBJECTIVE: To investigate the prognosis of patients of hydatidiform mole (HM) who
      complicated with pregnancy induced hypertension (PIH) and to suggest that PIH may
      serve as a risk factor for malignant change in molar pregnancy. METHODS: From
      1962 to 1992, 161 patients of HM including 33 cases with PIH and 128 cases of
      normotension were managed and followed at the PLA General Hospital. The
      definition of malignant sequelae was that abnormal hCG level was lasting at least
      8 weeks after molar evacuation or metastatic lesions was found. RESULTS: 15 of 33
      patients with PIH developed metastatic invasive moles (45.5%) and 13 of them
      metastatic tumors were found before molar evacuation. 12 of 128 cases of
      normotension had malignant thanges including 1 choriocarcinoma and 11 invasive
      mole (9.4%) and among them only one had metastatic lesions before molar
      evacuation. CONCLUSIONS: The incidence (45.5%) of malignant changes in patients
      complicated with PIH was significantly higher than that in normotensive patients
      (9.4%) (P < 0.01). In addition, they had early metastatic lesions. This study
      suggests that PIH may serve as a risk factor for malignant change in molar
      pregnancy.

PMID- 8745494
TI  - [Morphometric studies of effects of clomiphene citrate on histological
      characteristics of proliferative endometrium].
AB  - OBJECTIVES: To analyse quantitatively the effects of clomiphene citrate (CC) on
      histological characteristics of proliferative endometrium. METHODS: Endometrium
      biopsies were performed on day 12th of both natural and CC cycles in 14 infertile
      patients. Nuclear size, shapes and DNA contents of epithelial and glandular
      epithelial cells, stromal cells were measured or calculated after HE and Feulgeu
      staining by computerized image analysis technique. Results were compared before
      and after CC treatment. RESULTS: The average area, girth and maximal diameter of
      the nucler of glandular and epithelial cells in CC cycles were significantly
      smaller than those of natural cycles (P < 0.05), while the shape factor of
      stromal nuclea in CC cycles was larger than the natural ones (P < 0.05). DNA
      contents of glandular, epithelial and stromal nuclea in CC cycles were also
      smaller than those of natural cycles (P < 0.02). The difference of nuclear DNA
      content between the 2 cycles was positively correlated with the difference of
      nuclear area of glandular and epithelial cells (P < 0.01). CONCLUSIONS: CC
      treatment inhibited the endometrial mitosis and proliferation. This effects may
      begin at the stage of DNA synthesis, therfore DNA contents of endometrial
      glandular and stromal nuclea also decreased. The action of CC may be related to
      estrogen receptor synthesis.

PMID- 8745495
TI  - [Relationship between the fetal axis and dystocia in cephalic presenting
      deliveries].
AB  - OBJECTIVE: To study the relationship between the fetal axis and dystocia in
      cephalic presenting deliveries. METHODS: The fetal axis of the observed cases in
      their late pregnancy were measured by the method which was designed by anatomical
      projection. During labor the cases with abnormal fetal axis were divided randomly
      into control group and study group. The abnormal fetal axis in the study group
      was corrected by hand. RESULTS: The abnormal fetal axis existed in 108 of 512
      (21.1%) cases in late pregnancy and were divided into different degrees. The rate
      of severe degree was 51.8%. During labor 88 of 483 (18.2%) cases were severe
      degree. They were sub-divided into control group (30 cases) and study group (58
      cases). The results showed: in the study group the descent of fetal-presentation
      was accelerated, the stage of labor became shorter, the incidence of persistent
      occipito-posterior or occipito-transverse position and operative delivery were
      decreased, and the postpartum hemorrhage out down also. CONCLUSIONS: The
      abnormality of fetal axis exists and it can affect the progress of labor. The
      abnormal fetal axis should be diagnosed and corrected in time. To some extent, it
      can reduce the mother's physical consumption in labor and decrease the incidence
      of dystocia.

PMID- 8745496
TI  - [Diagnosis of meconium aspiration syndrome by fluorometry technique].
AB  - OBJECTIVE: To establish a new diagnostic method of neonatal meconium aspiration
      syndrome (MAS). METHODS: The fluorometry technique was used for examination of
      urine samples from three groups of neonates. The neonates were divided into 3
      groups: Group I, MAS (n = 17); Group II, no MAS, but amniotic fluid with meconium
      stain (n = 24); Group III, normal control (n = 27). Urine fluorescence meconium
      index (UFMI) and urine meconium index (UMI) were calculated. RESULTS: UFMI values
      of group I were higher than that of group II and III. The sensitivity and
      specificity of UFMI were 100% and 97% respectivety. However, it were 51% and 48%
      respectivety in UMI. CONCLUSIONS: UFMI is an index for identification of Zn
      coproporphycin, and it is a more sensitive index for diagnosis of MAS.

PMID- 8745497
TI  - [Risk factors on hyperglycemia in newborn infants].
AB  - OBJECTIVE: To investigate high risk factors of neonatal hyperglycemia. METHODS:
      According to the gestational age, postnatal age, weight, hypoxia, infection, 336
      hospitalized newborns receiving continuous intravenous infusion of glucose
      controlled by pump were divided into the study and control groups respectively,
      the incidences of hyperglycemia between two groups were analysed statistically.
      RESULTS: The results showed that the high risk factors of neonatal hyperglycemia
      were gestational age ( < 37 week), postnatal age ( < 72h), weight ( < 2 500g),
      hypoxia and (or) infection. CONCLUSIONS: In neonates with one or more high risk
      factors of hyperglycemia, strict control of infusion speed; treatment of original
      diseases and frequent monitoring of blood glucose should be noted.

PMID- 8745498
TI  - [Effect of ovarian cancer produced-transforming growth factor-beta on
      phytohemagglutinin and interleukin-2-inducing proliferation of peripheral blood
      mononuclear cells].
AB  - OBJECTIVES: Our previous observation has demonstrated that human ovarian cell
      lines COC1 and COC2 are able to secrete transforming growth factor-beta (TGF
      beta) in serum-free culture. The effect of ovarian cancer produced-TGF-beta was
      observed on phytohemagglutinin and interleukin-2-inducing proliferation of
      peripheral blood mononuclear cells. METHODS: The effects of COC1 and COC2 from
      patients' ascitic fluid (AS1, AS2), the serum-free conditioned medium (SFCM1,
      SFCM2), and COC1- and COC2- bearing nude mice sera (NS1, NS2) on
      phytohemagglutinin (PHA) and interleukin-2 (IL-2)-inducing peripheral blood
      mononuclear cell (PBMC) proliferation and their correlation with TGF-beta were
      observed and compared. RESULTS: It was shown that AS, SFCM and NS possessed
      inhibitory effects on PBMC proliferation. But in very low concentrations, PHA
      induced by SFCM2 and IL-2-induced by SFCM1 as well as by NS1 and NS2 exerted
      promotive effects on PBMC proliferation. The above-mentioned SFCM effects similar
      to that of TGF-beta, might be partially blocked by anti-TGF-beta antibody.
      CONCLUSIONS: The present results suggest that ovarian cancer cells may inhibit
      the host anti-tumor immunity through secreting TGF-beta, which may be associated
      with the highly malignant biological behavior of ovarian cancer and the
      threatening progressiveness of its clinical course.

PMID- 8745500
TI  - [Summary of the National Conference on Breast Feeding].

PMID- 8745499
TI  - [The p53 tumor suppressor gene and ovarian cancer].

PMID- 8745501
TI  - [Study of neonatal immunological function in breast feeding and formula feeding].
AB  - OBJECTIVE: To determine 4 immunoglobulins and soluble interleukin-2 receptor (sIL
      2R) in maternal and neonatal serum, in order to study the immunological functions
      in the neonates. METHODS: 80 cases were divided into three groups: (1) breast
      feeding group (30 cases), (2) formula feeding group (20 cases), and (3) mixed
      feeding group (30 cases). Maternal serum was collected prior to delivery and on
      the sixth day after delivery. Neonatal serum was collected on the third and sixth
      day after delivery. Umbilical blood at birth was obtained also. Secretory
      immunoglobulin A (SIgA), IgA, IgG, IgM and sIL-2R levels in the sera were
      determined by radioimmunoassay and enzyme-linked immunosorbent assay. RESULTS:
      The SIgA, IgA, IgG, IgM and sIL-2R levels in maternal serum were not
      significantly different among 3 groups, while neonatal serum SIgA, IgA, IgG, IgM
      and sIL-2R levels on the sixth day after delivery in the breast feeding group
      were significantly higher than those in the formula breeding group (P < 0.001, P
      < 0.001, P < 0.05, P < 0.05). CONCLUSION: Breast feeding may improve neonatal
      humoral and cellular immunity.

PMID- 8745502
TI  - [Secretory immunoglobulin A in human milk and infants' feces at 1-4 months after
      delivery].
AB  - OBJECTIVE: To determine the concentration of secretory immunoglobulin A (SIgA) in
      human milk at 1, 2, 3 and 4 months after delivery and in infants' feces in the
      same period and find out the effect of milk on the content of SIgA in infants'
      intestine. METHODS: 20 women and 12 breast feeding infants and 13 formula feeding
      infants were studied, and milk and infants' feces were collected at 1, 2, 3 and 4
      months after delivery, respectively. The concentrations of SIgA in milk and feces
      were determined by radioimmunoassay. RESULTS: No apparent changes in the
      concentration of SIgA were found in human milk and feces from breast feeding and
      formula feeding infants at 1-4 months after delivery, but the concentration of
      fecal SIgA in breast feeding infants was significantly higher than that in the
      formula feeding infants, during the first 4 months after birth. CONCLUSIONS:
      Human milk can provide a large amount of SIgA for infants. We conclude from these
      data that human milk is beneficial in protecting the immunological function of
      infants digestive tract.

PMID- 8745503
TI  - [The study of growth factors in human colostrum].
AB  - OBJECTIVE: To characterize and identify the growth factors in human colostrum and
      to evaluate the importance of breast-feeding. METHODS: The activity of growth
      factors in human colostrum was determined by technique of 3H-TdR incorporation
      into cultured NIH-3T3 cells. The acid growth factor (CAGF) and basic growth
      factor (CBGF) were purified from human colostrum by a sequence of chromatography.
      The study of stability and SDS-PAGE was applied to identify the CAGF and CBGF.
      RESULTS: 0.5% (v/v) of human colostrum and 3.0% (v/v) of bovine serum had the
      same activity in stimulating DNA synthesis. The specific activity of human
      colostrum in stimulating DNA synthesis was 20 times greater than that of bovine
      serum. The activity of growth factors in human colostrum was higher than that in
      human milk or bovine colostrum, and only human colostrum contained two different
      kinds of growth factors--CAGF and CBGF. CONCLUSIONS: Human colostrum contains two
      kinds of growth factors. CAGF is epidermal growth factor like (EGF-like) growth
      factor and the CBGF is platelet differentiation growth factor like (PDGF-like)
      growth factor. The effects of human colostrum on promoting baby growth and
      development is stronger than that of human milk and bovine colostrum.

PMID- 8745504
TI  - [A study on two gut hormones in breast milk].
AB  - OBJECTIVE: To determine if motilin and gastrin are present in breast milk and to
      measure their concentrations in human milk and cow milk. METHODS: The
      concentration of motilin was measured in 17 samples of human colostrum, 18
      samples of human mature milk, 8 samples of cow colostrum and 20 samples of cow
      mature milk by radioimmunoassay. The concentration of gastrin in human milk was
      also determined by radioimmunoassay. RESULTS: Motilin concentration in human
      colostrum was the highest (416.34 +/- 183.95ng/L), being higher than that in
      human mature milk (272.91 +/- 148.73ng/L, that in cow colostrum (229.51 +/-
      63.68ng/L) and that in cow mature milk (35.46 +/- 16.94ng/L). Evidently the
      difference in motilin concentration was very significant between human milk and
      cow milk. The gastrin concentration in human colostrum was 17.20 +/- 11.98ng/L,
      being higher than that in human mature milk (5.62 +/- 2.33ng/L). CONCLUSION:
      Human milk, especially human colostrum, contains high concentrations of motilin
      and gastrin. Breast feeding, especially early breast feeding, may promote the
      maturation of the developing gut in neonates and infants.

PMID- 8745505
TI  - [Direct genotyping and antenatal diagnosis of deletional alpha-thalassemia of the
      southeast Asian type by polymerase chain reaction technique].
AB  - OBJECTIVE: To study the gene of deletional alpha-thalassemia of the Southeast
      Asian type (SEA) and to perform the antenatal diagnosis. METHODS: A new method of
      polymerase chain reaction technique using three primers bridging the breakpoints
      was carried out for carrier detection and antenatal diagnosis of deletional alpha
      thalassemia of the Southeast Asian type. A DNA fragment of about 630bp in size
      was amplified in case of--SEA alleles, while a 224 bp fragment was amplified in
      samples without the deletion. Homozygotes, heterozygotes, and normal subjects
      could be clearly distinguished with the present method. RESULTS: We used this
      method in the genotyping and antenatal diagnosis of 10 high risk pregnancies of
      alpha-thalassemia. 2 homozygotes, 4 heterozygotes, and 4 normal infants were
      found. CONCLUSION: The present method is simple and rapid in detection of
      carriers and antenatal diagnosis of the alpha-thalassemia of southeast Asian
      type.

PMID- 8745506
TI  - [The cervical ripening score by trans-perineum ultrasound].
AB  - OBJECTIVE: To evaluate cervical ripening in pregnancy at term by trans-perineum
      ultrasound. METHODS: The cervical length, cervical internal os width, cervical
      echo intensity, cervical position and distance between fetal presentation and
      vaginal external os were assessed by trans-perineum ultrasound (transducer
      3.5MHz) in 100 cases of normal pregnant women at term. RESULTS: On the basis of
      Bishop score, the results showed, cervical ripening score > or = 9, 14 cases were
      in labor, mean parturient time 3.9 +/- 3.1 hours; 5 approximately 8 scores, 54
      cases were in labor, mean parturient time 20.8 +/- 3.9 hours; < or = 4 scores, 32
      cases in which only 21 cases were in labor, mean parturient time 46.9 +/- 3.9
      hours. The results were significantly different among the three groups.
      CONCLUSION: Ultrasonographic cervical ripening score is an objective noninvasive
      method for assessment of cervical ripening at term.

PMID- 8745507
TI  - [Research on the relationship between estrogen receptor, progesterone receptor,
      cell proliferation associated antigen in uterine leiomyoma and nuclear body
      density of myoma, serum reproductive hormone concentrations].
AB  - OBJECTIVE: To study the role of sex hormones in the pathogenesis of uterine
      leiomyoma in order to provide theoretical basis for medical treatment. METHODS:
      Estrogen Receptor (ER), progesterone receptor (PR) and cell proliferation
      associated antigen (Ki-67) contents of both normal uterine myometrium and
      leiomyoma were quantitatively analysed by ABC method and image analyser system
      (IAS) in 30 and 19 specimens obtained during hysterectomy respectively. Nuclear
      body density were also measured in 8 of them under electronic microscope. Serum
      luteinizing hormone (LH), follicular stimulating hormone (FSH), estradiol (E2)
      and progesterone (P) concentrations were determined by radioimmunoassay in 22
      cases on the operation day. 21 age-matched normal cycling women served controls.
      RESULTS: Contents of ER, PR, Ki-67 and the number, volume densities of nuclear
      body were significantly higher in leiomyoma than those in normal myometrium (P <
      0.01, P < 0.05). ER,PR contents of the two tissues in proliferative phase were
      greater than those in secretory phase, (P < 0.05), while Ki-67 contents were the
      opposite (P < 0.01). ER, PR contents of leiomyoma did not correlate with serum E2
      and P concentrations, but correlate negatively with serum LH and FSH levels (P <
      0.050). Ki-67 contents correlated positively with serum P levels and also showed
      inverse correlation with serum LH. FSH concentrations (P < 0.05). ER of leiomyoma
      positively correlated with density of nuclear body (P < 0.05). CONCLUSION: High
      ER, PR and Ki-67 contents in leiomyoma, may be the result of local high E2, P
      concentrations, and cause growth and development of leiomyoma. High Ki-67 content
      in secretory phase may indicate that progesterone has a synergistic effect in the
      pathogenesis of leiomyoma.

PMID- 8745508
TI  - [A study on the relationship between human papillomavirus and the incidence of
      cervical carcinoma].
AB  - OBJECTIVE: To determine the relationship between the infection by human
      papillomavirus (HPV) and the incidence of cervical carcinoma. METHODS: Biopsy and
      paraffin wax embedded specimens (n = 99) from various cervical lesions in the
      department of gynecologic oncology were analysed by polymerase chain reaction
      (PCR) technique with multiple primers of HPV types 6b/11, 16 and 18. RESULTS: Of
      99 cervical specimens investigated, 20 were histopathologically diagnosed as
      cervical condyloma, 18 as cervical intraepithelial neoplasia (CIN) grade 1
      approximately 2 (CIN1 approximately 2), 20 as CIN grade 3 (CIN3), 23 as cervical
      cancer and 18 as normal controls. Detection for HPV revealed that the positive
      rates of the five different groups were 85.0%, 83.3%, 80.0%, 87.0% and 27.8%,
      respectively. Those of the cervical lesions were significantly higher than that
      of the normal controls (P < 0.01). The predominant HPV type in condyloma and CIN1
      approximately 2 group were HPV 6b/11 (positive rates 85.0% and 72.3%), while HPV
      16 and (or) 18 DNA were more frequently found in the the CIN3 group (50.0%) and
      in the cervical cancer group (73.9%), The difference of distribution of HPV types
      in cervical condyloma, CIN1 approximately 2 and in CIN3, and cervical carcinoma
      was statistically significant (P < 0.01). CONCLUSION: HPV infections are
      intimately linked to condyloma, CIN and carcinoma of the uterine cervix; the low
      risk types HPV 6 and 11 seem to be associated with cervical condyloma and the low
      grade CIN; the high-risk types 16 and 18 are closely related to high grade CIN
      and cervical carcinoma.

PMID- 8745509
TI  - [Pelvic recurrence of cervical cancer: the prognostic relationship to the
      retreatment modalities].
AB  - OBJECTIVE: To investigate the prognostic factors in relation to retreatment
      modalities in patients with recurrent cervical carcinoma. METHODS: According to
      initial therapy, 194 patients with recurrence were grouped as: (1) surgery, 22
      cases; (2) surgery and radiotherapy, 24 cases, and (3) radiotherapy alone, 148
      cases. Factors such as clinical stage, sites of recurrence, time of diagnosis of
      recurrence after initial therapy and modalities of retreatment were analyzed.
      RESULTS: There were 19 cases alloted to stage I, 51 cases to stage II (IIa 23 and
      IIb 28) and 124 cases to stage III (IIIa 21 and IIIb 103); histopathologically
      confirmed squamous cell carcinoma in 181 cases and adenocarcinoma 13 cases.
      Central recurrences were found in 91 cases and lateral or pelvic recurrences in
      103 cases. Time of diagnosis of recurrence within 2 years from initial treatments
      was shown in 118 patients and above 2 years in 76 patients. In 147 of the 194
      patients retreated, those of the group 1 obtained a median survival rate of 24
      months, which was significantly longer than that of group 2, and group 3. The
      sites of recurrence did not significantly affect the survival. CONCLUSION:
      Radiotherapy remains the treatment of choice for patients with pelvic recurrence
      after surgery. Previously irradiated patients retreated for recurrence by
      radiotherapy and (or) chemotherapy had lower response rates. The optimal therapy
      for these patients should be comprehensive managements including surgery,
      radiotherapy and chemotherapy.

PMID- 8745510
TI  - [Primary malignant lymphoma of the female genital tract clinical analysis of 15
      cases].
AB  - OBJECTIVE: To review fifteen cases with primary malignant lymphoma of the female
      genital tract at Cancer Hospital, Chinese Academy of Medical Sciences from 1980
      approximately 1994. METHODS: This is a clinical retrospective analysis. There
      were 7 cases of lymphoma originating in the cervix, 2 in the vagina, 3 in the
      ovary, 1 in the vulva, endometrium and pelvic cavity respectively. All of the 15
      cases were given combination therapy. 3 ovarian lymphoma were treated by surgery
      and chemotherapy, 2 cervical lymphoma and 1 endometrial lymphoma by surgery,
      chemotherapy and radiotherapy, 1 pelvic lymphoma by surgery and radiotherapy,
      others by radiotherapy and chemotherapy. RESULTS: Two patients are living more
      than 5 years, 3 patients more than 3 years. 4 patients were followed up for less
      than 2 years and 6 patients relapsed or died. CONCLUSIONS: The prognosis of
      ovarian lymphoma is worse than that of other genital sites. Combined and
      sequential chemotherapy-radiotherapy-chemotherapy is the proper treatment
      sequence for lymphoma of the cervix, vagina and vulva. Extensive chemotherapy may
      be an appropriate choice for highly malignant pathological type. Radiation should
      be given early for large cervical lymphoma.

PMID- 8745511
TI  - [Fetal admission test and fetal heart rate response to vibratory stimuli test].

PMID- 8745512
TI  - [Pelvic abscess induced by peritoneal tuberculosis].

PMID- 8745513
TI  - Fine matrix mapping of the macular region in normal subjects.
AB  - Using a Humphrey field analyzer and fine matrix mapping, we measured photopic and
      scotopic thresholds for a blue light stimulus at 100 locations on a 9 degrees by
      9 degrees matrix of 1 degree spacing centered at the fovea in 14 normal subjects.
      Additionally, trial lenses were used to investigate the effect of refractive
      error. Under photopic conditions the mean sensitivity varied by less than 1 dB
      over this region. Under scotopic conditions the central values were reduced in
      sensitivity by 15 dB compared with those at 4 degrees eccentricity. Defocus
      showed less than 1.2 dB loss with 1.00D of refractive error under photopic
      condition. The results reflect the properties of rod and cone photoreceptors and
      the effects of the rod mosaic near the fovea. This technique is a sensitive test
      of macular visual function.

PMID- 8745514
TI  - [A comparison of attachment rates between SF6 and silicone oil tamponades
      following vitrectomy for treatment of complicated retinal detachment].
AB  - In this study, 215 eyes with rhegmatogenous retinal detachment and proliferative
      vitreoretinopathy (PVR) including giant tears, macular holes, perforating injury
      and traction caused by retinal vascular diseases were treated by vitrectomy and
      SF6 or silicone oil. The anatomic attachment rates were compared between gas and
      silicone oil groups in non-vitrectomized eyes and previously vitrectomized eyes,
      respectively. Both gas and silicone oil groups showed higher attachment rates in
      stage C of PVR, giant tears with PVR less than stage C2 and macular holes. The
      gas group showed lower attachment rates in cases with stage D of PVR, giant tear
      larger than 180 degrees or with PVR C3 or greater than C3, after perforating
      injury and traction-rhegmatogenous retinal detachment, while silicone oil group
      showed better attachment rates. The choice of tamponades should be based on
      different indications.

PMID- 8745515
TI  - [Treatment of intraocular fibrin formation with tissue plasminogen activator
      after vitrectomy].
AB  - Twenty two eyes of 22 cases with severe intraocular fibrin formation after
      vitrectomy who had been all unresponsive to conventional therapy were treated
      with tissue plasminogen activator (t-PA), including complicated retinal
      detachment (14 eyes), intraocular foreign body (3 eyes), vitreous hemorrhage (2
      eyes), traumatic cataract (2 eyes) and endophthalmitis (1 eye). The fibrin
      formation appeared 1-5 days with a mean of 2 days after operation. Of these 22
      eyes, fibrin was seen in the pupillary area in 11, in the anterior chamber in 10
      eyes and in the vitreous cavity in 1 eye. The initial injection of t-PA was given
      between the 5th and 15th (mean, 8.6 days) postoperative days after vitrectomy.
      The t-PA (5-30 micrograms) was injected into the anterior chamber in 21 cases and
      into the vitreous cavity in 1 case (25 micrograms). Once injection resulted in
      complete fibrinolysis in 19 of 22 eyes and partial fibrinolysis in 3 eyes, and
      the complete dissolution with one injection was achieved within 0.5-2.5 hours
      with a mean of 1 hour. 1 eye required repeated t-PA injection for recurrent
      fibrin formation and the repeated injection resulted in complete fibrinolysis in
      this case. The follow-up periods ranged from 1 to 20 months (mean period, 10
      months). At the final follow-up examination, the retina was totally attached in
      16 of 22 eyes and partially attached and detached in 6. Visual acuity improved in
      13 eyes. Complications of t-PA injection included hyphema, elevated intraocular
      pressure (IOP) and hyphema with elevated IOP in 1 case respectively. Factors
      affecting the therapeutic effect of t-PA and methods preventing the complications
      of t-PA injection were discussed.

PMID- 8745516
TI  - [Use of perfluorodecalin in giant retinal tear retinal detachment surgery].
AB  - Perfluorodecalin is used for the treatment of 11 eyes with giant retinal tear
      retinal detachment surgery. Perfluorocarbon liquids can be used as an operative
      hydrodynamic tool during vitreous surgery. The high specific gravity of
      perfluorocarbon liquids allows an easy unfolding of the inverted flap and
      flattening of the retina, displacing the subretinal fluid and stabilizing the
      retina for membrane peeling. Endophotocoagulation may be performed under optimal
      visual condition. The success rate was 81.8% (9/11). The retina failed to
      reattach in patients with advanced proliferative vitreoretinopathy. The surgical
      techniques were discussed.

PMID- 8745517
TI  - [Vitrectomy for treatment of vitreous hemorrhage associated with age-related
      macular degeneration].
AB  - Age-related macular degeneration (AMD) is an aging disorder which has been a
      leading cause for blindness among old people. The wet type AMD is the main cause
      which deteriorates visual function rapidly because of the complications including
      detachment of retinal pigment epithelium, formation of subretinal neovascular
      membrane and scar, subretinal and vitreous hemorrhage. This assay reports the
      results of vitrectomy for treatment of 10 cases with vitreous hemorrhage
      associated with AMD. The follow-up periods ranged from 1/2 to 28 months. The
      visual acuities in 9 cases were increased and in 1 case decreased. The factors
      affecting the postoperative visual acuity, operative complications and
      therapeutic prospects of the surgery were discussed.

PMID- 8745518
TI  - [The correlation between changes of static central visual fields and posterior
      polar lesions in high myopia].
AB  - The static central visual fields tested by an Octopus Field Analyzer and
      posterior polar lesions in 53 cases with high myopia were investigated. Cases
      with low and moderate degrees of myopia were the controls. The results
      demonstrate that the visual field defects are present in the high myopic eyes and
      they are related to the degree of high myopia, the age of the patient and the
      severity of the posterior polar lesion. The visual field defects present
      multiform and multilevel in character and they do not completely correspond to
      the fundus lesions. The appearance of central relative scotomata in high myopic
      eyes detected by a quantified automated perimeter is prior to the appearance of
      macular lesions seen under an ophthalmoscope. Therefore, the quantified automated
      central visual field examination is helpful to the early diagnosis of macular
      disease in high myopia.

PMID- 8745519
TI  - [A clinical observation on intraocular lens implantation in high myopic eyes with
      cataract].
AB  - Extracapsular cataract extraction (ECCE) with intraocular lens (IOL) implantation
      was performed on 124 high myopic eyes with cataract of 101 cases whose mean
      period of follow-up was 16.4 months. Post-operatively, 95.97% of these eyes were
      relieved from blindness and 75.00%, from visual handicap. The incidence of
      posterior capsular opacity was 22.58% and only did 1.61% of the eyes occur
      retinal detachment. Intraoperatively, posterior capsular rupture occurred in
      5.65% of the eyes. The results indicate that ECCE with IOL implantation performed
      on eyes with high myopia and cataract is effective.

PMID- 8745520
TI  - [Peribulbar anesthesia and intraocular lens implantation].
AB  - We studied the effectiveness of peribulbar anesthesia in 146 patients undergoing
      cataract surgery and intraocular lens implantation. The results revealed that the
      analgesic and akinetic effects obtained from peribulbar anesthesia are the same
      as or even better than that obtained from retrobulbar anesthesia. In the mean
      time, the use of peribulbar injection can avoid or reduce the serious
      complications associated with the retrobulbar injection. In this report, the
      method of peribulbar anesthesia was introduced and its mechanisms and
      effectiveness were discussed. The pre- and post-anesthetic intraocular pressures
      were especially observed and compared. It is safe to perform the operation 10
      minutes after the administration of the peribulbar anesthesia.

PMID- 8745521
TI  - [Posterior chamber intraocular lens implantation in diabetics].
AB  - 93 eyes having undergone extracapsular cataract extraction with posterior chamber
      intraocular lens implantation were evaluated prospectively. There were two groups
      of patients, including 38 diabetics with or without nonproliferative retinopathy
      and 38 nondiabetics. The comparison between the two groups demonstrated that
      there was no significant difference in intra-operative or postoperative
      complications. The post-operative corrected visual acuities of 0.5 or better were
      achieved in 26 of 47 (55.3%) of diabetic eyes and in 30 of 46 (65.2%) of
      nondiabetic eyes (P > 0.05). Based on this study, it is considered that
      nonproliferative diabetic retinopathy is not a contraindication of intraocular
      lens implantation. However, post-operatively, diabetic patients should be
      followed more closely and if any post-operative complication does occur, it
      should be treated promptly.

PMID- 8745522
TI  - [A study on stretching capacity of continuous circular capsulorhexis and nucleus
      delivery].
AB  - The stretching capacity of continuous circular capsulorhexis (CCC) in 20 human
      cadaver eyes was determined. The increases in circumference of the tear opening
      ranged from 164. 5% to 190.9% and that in area of the opening ranged from 235.2%
      to 364.6%. If a proper technique of capsulorhexis is adopted, the nucleus of 7
      9.5 mm in diameter and 3-4.5mm in thickness can be delivered through a CCC
      opening of 4-6mm in diameter by hydrodissection and hydroexpression of nucleus
      without capsular tear.

PMID- 8745523
TI  - [An analysis of ocular manifestations in cases with tumors of accessory nasal
      sinuses].
AB  - The ocular manifestations of 60 cases with tumors of accessory nasal sinuses were
      reported. They were proptosis, impairment of ocular movement, diplopia, decrease
      or loss of visual acuity, ptosis, etc. Of them, 42 patients came to the
      ophthalmology department first. All the patients were diagnosed by computerized
      tomography (CT scan) and pathological findings. Operative treatment was applied
      in 48 cases. 32 cases had improvement in ocular symptoms. Particular attention
      was paid to the analysis of the causes of the patients, ocular symptoms and
      signs. They are due to the close anatomical relationship between accessory nasal
      sinuses and the orbit and optic nerve canal. CT scan is helpful to the early
      diagnosis of the disease.

PMID- 8745524
TI  - [The differences in corneal shape between myopic and normal eyes].
AB  - The corneal shapes of 35 eyes with moderate and mild degrees of myopia compared
      with those of 35 normal eyes were studied by a computerized video keratoscope
      (TMS-1). The results show that the surface regularity index (SRI), the refractive
      power at central optical zone, the simulated keratoscopic reading (Simk), the
      average corneal power of zones 3mm, 5mm, 7mm in diameter centered at the corneal
      center of the eyes with moderate and mild degrees of myopia are greater than
      those of the normal eyes (P < 0.05). However, the surface asymmetry index (SAI),
      the differences of corneal powers between the first and the 15th ring and between
      the first and the 25th ring in both groups are of no statistical significant
      differences (P > 0.05). It is suggested that the corneal refractive power of
      myopic eye be much higher than that of the normal eye. The authors propose the
      first time that the pathogenesis of some eyes with moderate and mild myopia may
      be the increase of corneal refractive power which results from traction of sclera
      near the limbus due to accommodation and discuss it in detail.

PMID- 8745525
TI  - [A preliminary report on changes in micro-circulation of conjunctiva in patients
      with high altitude pulmonary edema].
AB  - Micro-circulation of conjunctiva was investigated in 36 patients with high
      altitude pulmonary edema (HAPE) and 21 healthy subjects who arrived recently in
      high land and were the controls, and plasma angiotensin II (AT II) and
      aldosterone (ALD) were determined in 16 patients with HAPE and in the control
      group. The results show that the concentrations of plasma AT II, ALD in patients
      with HAPE are obviously higher than those of the healthy individuals (P < 0.001),
      the degree of changes in micro-circulation of conjunctiva in patients with HAPE
      is directly proportional to the degree of severity of HAPE, and the higher the
      concentrations of plasma AT II and ALD, the severer the degree of changes in
      micro-circulation.

PMID- 8745526
TI  - [Measurement of velocity of ophthalmic arterial blood flow in normal persons with
      color Doppler sonography].
AB  - The authors measured the velocity of the ophthalmic arterial blood flow with
      color Doppler sonography (Acuson-128, USA) in 246 eyes of 123 normal persons to
      evaluate exactly the changes of the blood supply in all ischemic fundus diseases
      and provide the reliable reference basis for the clinic. The average velocity of
      the ophthalmic arterial flow of the normal in the maximum contraction period
      (peak systolic velocity, PSV) is respectively 36.44 +/- 8.35cm/sec on the right
      and 36.94 +/- 11.30cm/sec on the left. There were no significant differences in
      PSV between the right and left eyes and between the male and female persons. We
      found that PSV of the ophthalmic artery in persons over 41 years old was
      significantly different from that in persons below that age, suggesting the age
      of 41 years old be the beginning of the senile process of systemic small blood
      vessels and providing a reference for anti-sensility. In the mean time, the
      velocity of ophthalmic arterial blood flow was also evaluated in 18 eyes with the
      acute attack of acute angle-closure glaucoma and 15 eyes at pre-clinical stage.

PMID- 8745527
TI  - [Expression of insulin-like growth factor-I gene in normal and diabetic rat eye].
AB  - The expression of insulin-like growth factor I (IGF-I) gene was studied in both
      normal and diabetic rat eyes via in situ hybridization. The results revealed the
      regional expression of IGF-I gene in the rat eyes. The expression of IGF-I mRNA
      in the internal nuclear layer and ganglion cell layer is strong, in choroid,
      retinal pigment epithelium and external nuclear layer is moderate, in sclera is
      weak in degree and no such mRNA is detected in the cornea. The abundance of IGF-I
      mRNA in diabetic eye tissues is significantly (P < 0.05 or P < or = 0.01) higher
      than that in normal eye. These findings suggest that (1) functionally, the eye
      ball be considered to be an "IGF-I paracrine-autocrine system", and (2) the high
      expression of IGF-I indicate its initiation of diabetic retinopathy and its
      promotion of the progression of the lesion.

PMID- 8745528
TI  - [The influence of macrophage on the rates of cultured rabbit lens epithelial cell
      proliferation and DNA synthesis].
AB  - Cell and H3-TDR liquid scintillation countings were adopted to investigate the
      influence of macrophage on the proliferative rate of cultured rabbit lens
      epithelial cells, in vitro. After 24 hours of the action of macrophage opsonic
      fluid on the cell culture, the rates of cell proliferation and DNA synthesis in
      the experimental group were higher than those of the control group (P < 0.05) and
      maintained so to the fifth day. It is demonstrated that the macrophage and its
      active factors can promote the proliferation of the lens epithelial cells, that
      is possibly related to the posterior capsular opacification after extracapsular
      cataract extraction.

PMID- 8745529
TI  - [Complications of radial keratotomy and their treatments].

PMID- 8745530
TI  - Cloning, expression and purification of the ligand-binding region of human IL-6R
      in E. coli and its preliminary functional identification.
AB  - The ligand-binding region of human IL-6R is taken as the target gene fragment to
      be cloned and expressed. With pET-3b as expressing vector, two recombinants pET
      6R(B) and pET-6R(B)4 have been constructed encoding the ligand-binding region (28
      kD) of hIL-6R and its dimmer (53 kD), respectively. After induction with IPTG,
      they produced two proteins rIL6R-28 of 28 kD and rIL6R-53 of 53 kD amounting to
      50% and 30% of total bacteria proteins, respectively. The expressed products were
      mainly recovered as inclusion bodies. After purification and renaturation, both
      of them were capable of augmenting the growth-stimulating effect of IL-6 on 7TD1
      cells, an IL-6 dependent cell line. The result of ELISA also revealed that both
      rIL6R-28 and rIL6R-53 had the obvious ligand-binding activity.

PMID- 8745531
TI  - Cloning and expression of Kluyveromyces fragilis LAC4 gene.
AB  - The genomic library of Kluyveromyces fragilis was constructed in E. coli TG1, and
      5 beta-galactosidase gene (LAC4) clones have been obtained from the library by
      complementation of the Kluyveromyces lactis lac4-8 mutation. The studies on the
      structure and the function of the LAC4 gene revealed that (i) the gene can also
      complement E. coli lacZ mutation; (ii) the physical map of the K. fragilis LAC4
      gene was very similar to that of K. lactis; (iii) the beta-galactosidase levels
      expressed by the clone strains were much higher than that expressed by the
      original strain; (iv) the variation of the beta-galactosidase level of different
      clone strains induced by lactose or galactose was related to the retained degree
      of the 5' flanking region of LAC4 gene, suggesting that there might be a lactose
      specific transcription activating element in the region.

PMID- 8745532
TI  - Construction, expression and characterization of tissue-type plasminogen
      activator mutants.
AB  - Three tissue-type plasminogen activator (t-PA) mutants were constructed by
      recombinant and site-directed mutagenesis techniques. They are del(296-302) with
      deletion of PAI-1 binding site, N117Q/N184Q with deglycosylation of K1 and K2
      domains, and their combination mutant designated as GGI. Then these three mutants
      were successfully transiently expressed in COS-7 cells, and GGI was further
      stably expressed in CHO cells. The biological characterization of the expression
      products indicated that del(296-302) and GGI possessed the resistance to
      inhibition by PAI-1. In addition, the specific activity of GGI was increased by
      about 46%, the plasma half-life was prolonged by about one fold, while its
      affinity for fibrin was not affected.

PMID- 8745533
TI  - Interference of electromagnetic waves in dynamic metabolism.
AB  - Life is a continuous process of the dynamic metabolism. The influence of
      electromagnetic waves on the process of metabolism cannot be neglected. Here a
      new theory of electromagnetic interference in the dynamic metabolism of life is
      proposed. The statistical dynamic equations of ion and free radical in the
      biochemical reaction radiated by electromagnetic waves are given. The intensity
      of electromagnetic interference could be described with an interference factor.
      Good agreement can be seen between the calculated and measured results for a
      famous experiment of radio-frequency radiation-induced calcium ion efflux
      enhancement.

PMID- 8745535
TI  - [Cystic fibrosis in adults].
AB  - OBJECTIVES: At least half cystic fibrosis patients now reach adulthood. METHODS:
      We report a population of 61 patients above 18 years of age with the clinical
      pictures at time of diagnosis and the present clinical status. RESULTS: Thirty
      five males and 26 females are aged from 18 to 47 years. Mean age at time of
      diagnosis was 5 years and 5 months, under 10 years in 80% of patients and above
      15 years in 9 patients. Diagnosis was suspected because of pulmonary (2/3) or
      digestive (1/3) symptoms, insufficient height and weight (1/3) or past family
      history of cystic fibrosis (1/3). 37% of patients are homozygotes for delta F508
      mutation. Adult patients had a normal height but half of them a body weight under
      90% of expected weight. Recurrent pulmonary infections were observed in 95% of
      patients and 62% have chronically infected sputum with Pseudomonas aeruginosa.
      These patients had lower weight and a poorer radiological score than patients
      without pseudomonas. 25% of all patients had chronic respiratory insufficiency.
      75% had pancreatic insufficiency and 6 patients diabetes mellitus. Thirteen
      patients had biological cholestasis and three a liver cirrhosis with portal
      hypertension. Four women underwent 6 normal pregnancies; semen analysis in five
      men revealed aspermia. Seven patients died during the last two years because of
      respiratory insufficiency (4), in the three months after pulmonary
      transplantation (2), and because of digestive haemorrhage (1). CONCLUSION:
      Treatment included daily bronchial drainage, adapted antibiotic treatment and
      pancreatic enzyme substitution.

PMID- 8745534
TI  - [Position and sudden death of the infant].
AB  - In western countries, the sudden infant death syndrome (SIDS) is the leading
      cause of mortality in infants under one year of age. In an official statement on
      prevention from the French Ministry of Health, sleeping in the supine position or
      on the side is recommended for all infants unaffected by a particular medical
      condition. This clear restrictive recommendation is based on valid
      epidemiological data but raises questions in the minds of paediatricians and
      general practitioners since the most recent recommendations for treatment of
      gastro-oesophageal reflux indicate that the prone position at a 30 degrees angle
      is the first preventive measure to be taken. We present here an objective view
      point on this complex problem which others may find helpful in developing a sound
      approach to each individual case. First it must be emphasized that multiple
      factors are involved in SIDS. While the confirmed correlation between the supine
      sleeping position and reduced incidence of SIDS is a valid rationale for
      population-based preventive measures, it does not indicate any causal
      relationship. Secondly, epidemiological data is valid for a given geographical
      area but cannot be extrapolated to other areas without taking into account
      intercurrent factors such as soft bedding, use of feather-bed quilts, excessive
      bedroom temperature and passive smoking. The public campaign for the prevention
      of SIDS should be encouraged as an effective low-cost measure, but both
      physicians and parents should be aware of its multifactorial nature in order to
      avoid psychologically catastrophic consequences of the guilt syndrome. For
      infants with uncomplicated simple gastro-oesophageal reflux, a formerly well
      known condition but currently less well tolerated by modern parents, it is
      essential to explain the physiological nature of the reflux to parents then to
      propose formula thickeners, antacids or prokinetic agents in particularly
      symtomatic cases. Sleeping in the 30 degrees prone position should not, in this
      particular case, be introduced as a preventive measure since the risk induced
      would probably be greater than the beneficial effect. For complicated reflux,
      after careful exploration and elimination of other causes of vomiting, treatment
      should be optimized first, followed by discussion on placing the infant in the 30
      degrees prone position which should be considered as a therapeutic tool with the
      same risk of secondary effects as expected with drugs.

PMID- 8745536
TI  - [Primary hyperparathyroidism. Relationships of symptoms to age, sex, calcemia,
      anatomical lesions and weight of the glands].
AB  - OBJECTIVES: Primary hyperparathyroidism is a polymorphic disease. We evaluated
      the effect of different factors on clinical expression. METHODS: Clinical
      expression in 259 patients who underwent surgery for primary hyperparathyroidism
      were analyzed as a function of patient age, sex, calcium level, anatomic lesions
      and weight of the diseased glands. RESULTS: Behaviour disorders and bone images
      were more frequent in women and urinary lithasis and gastric ulcers were more
      frequent in men. Behaviour disorders, bone images, chondrocalcinosis, renal
      failure and acute episodes were more frequent in elderly patients. Inversely,
      urinary lithiasis was more frequent in young subjects. The prevalence of
      asymptomatic forms was not related to the level of calcaemia, even for very high
      levels. Calcium levels above 3.5 mmol/l led to a significantly higher rate of
      behaviour disorders and acute episodes. Moderately elevated calcium levels were
      associated most frequently with urinary lithiasis. There was no evidence that
      anatomic lesions were related to symptomatology, particularly cancer which was
      not related with more frequent or more severe forms. Finally, nephrocalcinosis,
      renal failure and acute episodes were particularly frequent when the weight of
      the parathyroid tissue was greatest. CONCLUSION: The main therapeutic conclusion
      concerned primary hyperparathyroidism with moderately elevated calcium levels:
      since there is no difference between the clinical expression of primary
      hyperparathyroidism with moderately elevated calcaemia, the same surgical
      approach is recommended.

PMID- 8745537
TI  - [Non-specific pituitary responses in insulin-dependent diabetes mellitus in
      children and adolescents].
AB  - OBJECTIVES: Several reports indicate a number of changes in the control of the
      release of PRL, LH, FSH, GH and beta-endorphin (B-EP) as a result of insulin
      dependent diabetes mellitus (IDDM). In this study we evaluate the presence of non
      specific pituitary responses to releasing hormones in IDDM children and
      adolescents. METHODS: The non-specific effects of TRH on plasma GH, LH and B-EP
      levels and of GnRH on plasma GH, PRL, TSH and B-EP levels were measured in 16
      IDDM children and in 16 healthy children matched by age and sex. All subjects
      were tested with injection of TRH (200 micrograms i.v. bolus) and GnRH (50
      micrograms i.v. bolus). GH, TSH, PRL, LH and B-EP levels were evaluated with
      radioimmunological methods on blood samples collected before and after
      stimulation by releasing hormones. RESULTS: GH and B-EP non-specific responses to
      TRH and GnRH were significantly more pronounced in IDDM patients than in
      controls. All patients showed at least one non-specific response to one of the
      two releasing hormones. No significant correlations were found between non
      specific pituitary responses and the patient's age, the duration and onset of
      disease or the degree of metabolic control. CONCLUSIONS: These observations may
      indicate that: in IDDM hypothalamus-pituitary regulating mechanism is altered;
      the hormones whose levels are most often found to be abnormal in IDDM (other than
      insulin) are also hormones which respond non specifically to the neuropeptides
      TRH and GnRH.

PMID- 8745538
TI  - [Aneurysms of the popliteal artery. Intravascular bypass using the internal
      saphenous vein].
AB  - We used the internal saphenous vein to create an intravascular bypass for the
      treatment of aneurysms of the popliteal artery. The saphenous vein was positioned
      within the lumen of the aneurysmal popliteal artery and in the superficial
      femoral artery at its origin. Two end-to-end anastomoses were made including the
      venous wall within the suture. This new surgical technique is based on 3
      criteria. i) anatomic: the venous bypass follows the exact path as the artery
      since it is situated within the lumen; ii) haemodynamic: end-to-end anastomoses
      are used to avoid turbulence created with end-to-side sutures; iii) histologic:
      the venous endothelium protects better against thrombus formation ensuring good
      long-term permeability.

PMID- 8745539
TI  - [Type I hypersensitivity reactions and etiopathogenesis of hemorrhagic
      rectocolitis].
AB  - There is a body of clinical, epidemiological, biologic, histological and
      therapeutic data suggesting that type I hypersensitivity plays a role in the
      pathogenesis and maintenance of ulcerative colitis. Contradictory evidence from
      different studies on the pathogenic mechanisms may simply mean that there is not
      one but several types of ulcerative colitis. Chronic inflammation of the
      intestine would cover a heterogeneous group of conditions. Genetic susceptibility
      controlling one of more anomalies of the immune system would be triggered by
      external factors such as respiratory or food allergies, viral or bacterial
      infections or other factors including smoking or stress. The wide range of
      factors involved would explain the variety of findings reported by different
      groups searching for a single pathogenic mechanism. Finally, as emphasized by
      other authors, screening for subgroups of patients with allergy among the
      ulcerative colitis population would be useful in adapting treatment and
      developing a more specific therapeutic strategy not only for acute phases but
      perhaps also for preventive treatment.

PMID- 8745540
TI  - [Spontaneous displacement of the gallbladder. A rare cause of hemoperitoneum].

PMID- 8745541
TI  - [Cutaneous necrotic lesions in dermatomyositis in adults: a predictive sign of
      cancer?].

PMID- 8745542
TI  - [Polyvisceral and multirecurrent lymphoma].

PMID- 8745543
TI  - [Inflammatory pseudotumor of the small intestine: un unusual cause of intestinal
      intussusception in adults].

PMID- 8745544
TI  - [Interstitial pneumonia following treatment with alpha-interferon].

PMID- 8745545
TI  - [Isolation of meningococcal strains of decreased sensitivity to penicillin G in
      France].

PMID- 8745546
TI  - [Complete arrhythmia, caused by atrial fibrillation, causing ischemic cerebral
      vascular accident following acute alcoholic intoxication in a young subject].

PMID- 8745547
TI  - [Tuberculosis in a Parisian internal medicine hospital unit. 50 cases].

PMID- 8745548
TI  - [Evaluation of the efficacy and the tolerance of cicletanine in hypertensive
      subjects over 65 years of age. Three frequent clinical situations in urban
      practice].

PMID- 8745549
TI  - [Studies on bacterial metabolism pathway of 2-naphthoic acid].
AB  - The missing chemical Link (Phthalate) of bacterial metabolism pathway for 2
      naphthoic acid has been identified to be existing. The genetic regulation
      mechanism of 2-NAT strain for 2-naphthoic acid metabolism is also investigated
      with plasmid curing, transposon Tn10 mutagenesis and mutation reversion
      experiments. It is discovered that 2-NAT strain carries at least one plasmid. The
      plasmid and the chromosomal DNA co-encode and control the bacterial metabolism
      pathway for 2-naphthoic acid.

PMID- 8745550
TI  - [Isolation and reassociation of acetogen and methanogen in a syntrophobic
      coculture degrading butyrate anaerobically].
AB  - Anaerobic coculture BF2 which degraded butyrate into acetate and produced methane
      was isolated from granular methanogenic sludge. The coculture is associated
      syntrophically the Syntrophomonas subsp. saponavida strain CF2 with
      Methanobacterium formicicum strain MF2 and appeared to degraded C4 approximately
      C18 fatty acids including isobutyrate. The optimal temperature and pH for growth
      was 37 degrees C and 7.7 respectively. The strain CF2 was obtained in pure
      culture with crotonate as substrate and produces acetate and butyrate. The
      doubling time of strain CF2 in crotonate media was about 20 hours. Strain CF2 is
      Gram negative, slightly curved 0.2 approximately 0.3 x 2.0 approximately 3.0
      micron with round ends, motile by lateral flagellation at the concave side, non
      sporeforming. With a hydrogen scavenging organism, such as Methanospillum
      hungatei JF1, Methanobacterium formicicum 1535, Methanobrevibacterium bryantii
      1125 and Desulfovibrio sp. B11, the strain CF2 paired up and the defined
      coculture degraded butyrate to acetate. When the strain CF2 associated with the
      original accompanist, Methanobacterium formicius strain MF2, the reassociated
      couculture degraded butyrate to acetate and produced methane again.

PMID- 8745551
TI  - [Effects of SL-probiotic preparation on the body weight and phagocytosis of white
      mice].
AB  - Effects of SL-probiotic preparation on the body weight and the phagocytic
      functions in white mice were studied. Bioassay of its toxicity showed SL-P was
      non-toxic. Body weight of the treated mice increased significantly as compared
      with that of controls 10 days after treatment with SL-probiotic preparation.
      Phagocytic activity, acid phosphatase activity, lysozyme activity of the
      peritoneal macrophages of the tested mice were enhanced significantly as compared
      with those of normal controls. The same results were obtained with respect to
      serum lysozyme activity. These observations showed that SL-probiotic preparation
      could activate macrophage function in mice and hence enhancement of non-specific
      immunity.

PMID- 8745552
TI  - [Serogroups, virulence and hemolytic activity of Aeromon as hydrophila which
      caused fish bacterial septicaemia].
AB  - A new infected disease called bacterial septicaemia occurred in cyprinid fish
      throughout China during 1989-1992. A. hydrophila was known as the most important
      pathogen of this harmful disease. Thirty-three strains of A. hydrophila, most
      isolated from moribund fishes, were serogrouped by tube-agglutination with rabbit
      antisera. Most of the isolates could be grouped into two serotypes, TPS-30 and
      PBJS-76. These two groups could be found not only in Zhejiang province but in
      other province in south China. It can be concluded that the two serogroups were
      the main Aeromonas groups caused this fish disease. These isolates were virulent
      to Carassius auratus, with LD50 values of 10(4) to 10(6). The hemolytic activity
      ranged from titers of 1/8 to 1/16. No relationship were observed with the
      hemolytic activity and virulence.

PMID- 8745553
TI  - [Retrospect of a pharmacologist's life].

PMID- 8745554
TI  - [Genes and the modulation of learning and memory].
AB  - Recently, progress in the study of the relationship between gene and the
      modulation of learning and memory was noticeable. The studies showed that: (1)
      The expression of immediate early genes (IEGs), especially the c-fos, is a
      necessary prerequisite for the formation of memory; the induction of long term
      potentiation (LTP) is accompanied by an increase of IEGs expression; (2) Mice
      with deficiency of alpha-Calcium-Calmodulin Kinase II (alpha-CaMK II), or neural
      cell adhesion molecules (N-CAM) or tyrosine kinase gene (fyn) generated by gene
      targeting appear deficits in spatial learning and memory, mutation of alpha-CaMK
      II and N-CAM gene can also interfere with the induction and maintenance of LTP;
      (3) The single-gene mutants of Drosophilia (dnc, rut) showed significant decrease
      of the ability of memory. The mechanism is related to the altered synaptic
      plasticity, and the mushroom body may be the memory center of Drosophila.

PMID- 8745555
TI  - [Expression and regulation of milk protein gene in mammalia].
AB  - On the basis of introducing the structures and relations of evolution in milk
      protein genes, the factors involved in gene expression including cis-acting
      elements, trans-acting factors as well as induction of hormones were discussed.
      Finally the applicable prospect of mammary gland as a bioreactor was estimated.

PMID- 8745556
TI  - [The classes, structures, functions and signaling transduction of cytokine
      receptors].
AB  - There are many kinds of cytokine receptors that belong to different receptor
      families. Most cytokine receptors function as: (1) receptor tyrosine kinase and
      tyrosine-kinase-associated receptor; (2) receptor serine/threonine kinase; (3) G
      protein linked receptor. Following binding with cytokines and activation, the
      receptors trigger different cascade of intracellular protein phosphorylation to
      transduction signals, thereby altering the cell's pattern of gene expression and
      leading to biological effects.

PMID- 8745557
TI  - [The roles of thalamic nucleus submedius in nociception and pain modulation].
AB  - Recent studies on the roles of thalamic nucleus submedius (Sm) in nociception and
      pain modulation were reviewed in this article in combination with own our works.
      Results of these studies showed that Sm may be involved in effective-motivational
      aspects of pain, and that Sm-VLO-PAG may constitute a pathway of nociceptive
      modulation which may depress the nociceptive inputs at the spinal cord level via
      the brain-stem descending inhibitory system, thereby mediate a negative feedback
      regulation of pain.

PMID- 8745558
TI  - [Molecular and biological features of human CD34+ Hematopoietic stem/progenitor
      cells].
AB  - It is generally held that control of viability, proliferation, differentiation,
      maturation and programmed cell death events in hematopoietic stem/progenitor
      cells existing in a hierarchical fashion in vivo is a successively developmental
      process. The CD34+ antigen preferentialy expressed on hematopoietic
      stem/progenitor cells has so far been recognized as one of the earliest known
      antigens. Many advances on molecular structure of CD34 antigen would help us to
      understand deeply a lot of important questions regarding CD34+ hematopoietic
      stem/progenitor cells. These questions are, for instances, functional subclass,
      expression range and other biological properties including cell cycle state,
      fluorescent light scatter, ect. All of these studies would renew and consummate
      the modern concept of hematopoietic stem cells and the fundamental model of
      hematopoiesis and its regulation.

PMID- 8745559
TI  - [Study on a role of substance P in the spinal mechanisms of electroacupuncture
      analgesia].
AB  - It was found in the present study that low frequency (2Hz) electroacupuncture
      (EA) stimulation caused a decrease of the content of substance P immunoreactivity
      (SP-ir), whereas medium-(15Hz), high-(100Hz) and dense-disperse (D-D)- (2/15Hz)
      frequencies EA stimulation induced an increase of the content of SP-ir in the rat
      spinal fluid. EA analgesia induced by medium-, high- or D-D mode frequency was
      suppressed by nonpeptide SP (NK1) receptor antagonists CP96345 or RP67580
      administered intrathecally (i.t.). Both the attenuation of SP release by low
      frequency EA and the potentiation of SP release by medium frequency EA in the
      spinal cord were blocked by the opioid receptor antagonist naloxone (i.t.). These
      results suggest that a decrease of release of SP-ir by low frequency and an
      increase of it by medium-, high- and D-D mode frequencies in the spinal cord
      facilitate analgesia.

PMID- 8745560
TI  - [Experimental research of the effect of physical training on brain aging].
AB  - Physical training is an important means modifying brain aging. Using behavioral,
      morphological and biological methods, the present study investigated the effect
      of prolonged training (running wheel for 8 and 19 months), initiated at 5 months
      of age, on age-related changes of motor-associated centers in the mouse. The
      results suggested that a moderate amount of prolonged physical training could
      modify the age-related degenerative changes of morphology and function of neurons
      in motor-associated centers and improve the function of neurons through the
      stimulation of the compensation of neurons.

PMID- 8745561
TI  - [The neurite-outgrowth promoting effect from Clarke's nucleus of cat spinal cord
      with spared dorsal root preparation under electro-acupuncture stimulation on
      dorsal root ganglion of chicken embryo].
AB  - A modification of the double-coverslip hanging-drop culture technique originated
      from Maximow was introduced in the present report. The neurite - outgrowth
      promoting effect from Clarke's nucleus of cat spinal cord with partially
      lumbosacral dorsal rhizotomy as well as acupuncture stimulation of the points
      located within the peripheral innervating field of the spared dorsal root was
      examined with the modified culture technique. Findings demonstrated that an
      increased neurite-outgrowth promoting effect appeared in Clarke's nucleus of cat
      spinal cord with partial deafferentation, and that electro-acupuncture
      stimulation could enhance the neurite-outgrowth promoting effect further. It
      suggested that the increment of the neurite-outgrowth promoting effect might be
      related to the collateral sprouting of spared dorsal root and to the sprouting
      promotion effect of acupuncture stimulation.

PMID- 8745562
TI  - [Hypothalamic-pituitary stress hormones and serotonergic system in the brain].

PMID- 8745563
TI  - [Molecular biology of opioid receptor].

PMID- 8745564
TI  - [Biologic characteristics and physiological significances of M current].

PMID- 8745565
TI  - [Hepatocyte growth factor may accelerate the regeneration of nonhepatic tissues].

PMID- 8745566
TI  - [Regulation of liver regeneration after hepatectomy].

PMID- 8745567
TI  - [Effects of IL-2 on the central nervous system].

PMID- 8745568
TI  - [Recent advances in studies of IL-12].

PMID- 8745569
TI  - [Second messenger system and regulation of smooth muscle contractile activity in
      digestive tract].

PMID- 8745570
TI  - [Lipid mediators and liver injury].

PMID- 8745571
TI  - [Biological study of fullerene C60].

PMID- 8745572
TI  - [Beta-receptor and inflammation].

PMID- 8745573
TI  - Identification of 2-[125I] iodomelatonin binding sites in the thymus of mice and
      its significance.
AB  - The melatonin binding sites in membrane preparations of the mouse thymus were
      demonstrated using 2-[125I] iodomelatonin as a radioligand. The binding sites
      were stable, saturable, reversible and of high affinity. Studies on specificity
      of 2-[125I] iodomelatonin binding suggested that the 2-[125I] iodomelatonin
      binding sites are highly specific for melatonin. These binding sites fulfilled
      the standard criteria for receptors. Our work suggested that melatonin should
      have direct regulatory action on immune system mediated through the melatonin
      binding sites. Studies on the circadian rhythm showed that there existed the
      circadian rhythm in the binding capacity for 2-[125I] iodomelatonin in the mouse
      thymus with the peak values at 12:00-16:00 and the trough values between 00:00
      and 4:00. The subcellular distribution of 2-[125I] iodomelatonin binding sites in
      the mouse thymus was in the following descending order: nuclear > mitochondrial >
      microsomal > cytosolic fraction. There was also an age-related decrease in 2
      [125I] iodomelatonin binding in the mouse thymus. This is correlated with the
      involution of the thymus.

PMID- 8745574
TI  - 1D and 2D 1H NMR studies on bisantrene complexes with short DNA oligomers.
AB  - The binding of bisantrene to four DNA tetramers, d(CGCG)2, d(GCGC)2, d(CATG)2,
      and d(GTAC)2, was investigated by 1D and 2D NMR spectroscopy. Bisantrene is a
      well known anticancer drug and has been used clinically for years. DNA is
      believed to be one of its cellular targets. Results from both 1D and 2D 1H NMR
      are in agreement with an intercalation binding mode of bisantrene with the four
      DNA tetramers in this study. The results further indicate that a threading
      intercalation binding mode, in which one bisantrene side chain is in the minor
      groove and the other in the major groove of DNA, is preferred. The NMR results
      also suggest that bisantrene prefers binding at pyrimidine-(3',5')-purine
      intercalation sequences rather than at purine-(3',5')-pyrimidine sequences. The
      intramolecular and intermolecular NOE contacts of bisantrene-DNA tetramer
      complexes indicate that a C2'-endo uniform sugar pucker, rather than a mixed
      sugar conformation, is preferred by the intercalation site of both the 5'-(TA)-3'
      and the 5'-(CG)-3' binding steps.

PMID- 8745575
TI  - Relationship between the induction of heat shock proteins and the decrease in
      glucocorticoid receptor during heat shock response in human osteosarcoma cells.
AB  - Previously, it has been found that glucocorticoid receptor (GR) binding activity
      decreased rapidly during heat shock response in HOS-8603, a human osteosarcoma
      cell line. In this study, The relationship between the induction of heat shock
      proteins (HSPs) and the decrease in GR was further studied in the same cell line.
      It was found that even though quercetin could specifically inhibit the expression
      of hsp90 alpha and hsp70 mRNA, it could not prevent GR from the decrease in
      response to the heat shock treatment. This represents the first reported evidence
      that the induction of HSPs and the decrease in GR during heat shock response were
      2 independent biological events. The results of the present study further showed
      that although the heat shock treatment alone had no effects on alkaline
      phosphatase (AKP) activity, it could completely block the induction of AKP
      activity in HOS-8603 cells by dexamethasone (Dex), a synthetic glucocorticoid.
      These results demonstrate that the heat shock-induced alteration in GR was
      accompanied by a decrease in GR functional activity. Furthermore, when the
      induction of HSPs was inhibited by the treatment of cells with quercetin, the
      stimulatory effects of Dex on AKP activity could still be inhibited completely by
      the heat shock treatment. The results of this part, on the basis of GR functional
      activity, further demonstrate that quercetin could not inhibit the heat shock
      induced decrease in GR even though it could inhibit the induction of HSPs. To
      clarify further the effects of quercetin alone on GR binding activity in HOS-8603
      cells, the regulation of GR by quercetin was also studied. It was found for the
      first time that quercetin could down-regulate GR in a time-dependent manner
      significantly, and that the down-regulation of GR by quercetin in HOS-8603 cells
      paralelled with a decrease in glucocorticoid-mediated functional responses,
      suggesting that the down-regulation of GR by quercetin is of biological
      significance.

PMID- 8745576
TI  - Effect of phorbol ester on cAMP-dependent protein kinase activity in
      cardiomyocytes.
AB  - Cardiomyocytes isolated from neonatal rats were treated with phorbol-12-myristate
      13-acetate (PMA) ranging from 10(-11) to 10(-7) mol/L for 20 min, causing cytosol
      protein kinase A (PKA) activity to decrease while particulate PKA activity
      increase in a concentration-dependent manner. The change of PKA activity induced
      by PMA was abolished completely by pretreatment of polymyxin B or depletion of
      protein kinase C (PKC). Type II PKA activity in particulate fraction was enhanced
      remarkably, while that of type I PKA was not altered when the cells were treated
      with 100 nmol/L PMA. The results suggested that subcellular distribution and
      activity of PKA in cardiomyocytes may be regulated by PKC.

PMID- 8745577
TI  - Taxonomic status of car bacillus based on the small subunit ribosomal RNA
      sequences.
AB  - In an attempt to identify the taxonomic relationship between CAR bacillus and
      other bacteria, the SSU rRNA gene sequences of two CAR bacillus strains, CBM and
      CBR isolated from mice and rats respectively were used in the present studies.
      The SSU rRNA gene sequences, approximately 1.5 kb in size amplified from genomic
      DNAs from both strains, were determined and 96.8% homologies were found to exist
      between them. Those sequences were aligned to most eubacteria with a computer
      search showing high homology with those of Flavobacter/Flexibacter species
      especially closed to Fx. sancti and Fv. ferrugineum. Phylogenetic analysis
      indicated that CAR bacillus belongs to a species close to Fx. sancti and Fv.
      ferrugineum subdivision.

PMID- 8745578
TI  - Expression of p53 gene in oral squamous cell carcinoma and its relation with
      clinical and pathological parameters and prognosis of patients.
AB  - One hundred and eleven cases of oral squamous cell carcinoma (OSCC) were examined
      for overexpression of p53 protein by using immunohistochemical technique.
      Association between p53 protein overexpression and clinical and pathological
      parameters as well as prognosis of patients were also analyzed. p53 protein
      overexpression was commonly observed (69.4%) in OSCC and may be used as a marker
      of carcinogenesis of OSCC. The level of p53 protein overexpression is correlated
      with the lower three and five-year survival rate of OSCC. The presence or absence
      of p53 overexpression was not correlated with sex, age, site of tumor, size of
      tumor, degree of differentiation, node status, and clinical stage in OSCC. Single
      factor COX proportional hazards regression model analysis indicated that there
      was no significant association between p53 overexpression and prognosis of OSCC.
      Multivariable COX model analysis failed to establish effective life function or
      risk rate function. These showed that all the parameters analyzed in this study
      as well as p53 overexpression were not significant and effective risk factors of
      prognosis for patients with OSCC.

PMID- 8745579
TI  - A diagnostic practice study using international classification of epilepsies and
      epileptic syndromes in 302 cases.
AB  - We attempted to classify, according to the International Classification of
      Epilepsies and Epileptic Syndromes (1989), 302 patients at a tertiary epilepsy
      referral center. Proportion in categories as defined by the International League
      Against Epilepsy (ILAE) were as follows: localization-related epilepsies: 62.9%,
      generalized epilepsies: 22.2%, epilepsies undetermined whether focal or
      generalized: 14.2%, special syndromes: 0.7%. Only 26.8% cases were definitely
      classified in single diagnostic ILAE categories based on ictal CCTV/EEG
      recordings. The distribution of epileptic syndromes was different from the
      previous reports due to various methods of case ascertainment and inclusion
      criteria. Use of specific criteria for the reliability study of international
      classification has been proposed.

PMID- 8745580
TI  - The role of recombinant human fusion protein IL-6/IL-2 (CH925) in hepadna virus
      infection treatment.
AB  - The effects of CH925, a novel immune modulator, on hepadna virus infection was
      evaluated. Day-old ducklings were inoculated intravenously with LJ-76 DHBV
      containing serum. Infected ducklings were then treated with the CH925 and the
      mixture of IL-2 and IL-6 intravenously and the control ducklings received
      equivalent normal saline (NS). Blood and liver samples were taken and assayed for
      DHBV DNA and/or DHBsAg. At the completion of the experiment there was a
      inhibition of viremia with the CH925 and IL-2 + IL-6. Serum DHBV DNA was detected
      in 6 of 10 ducks in 100,000 unit/kg dosage group, 7 of 10 ducks in 50,000 unit/kg
      dosage group and 6 of 10 ducks in IL-2 + IL-6 dosage group, compared with 9 of 10
      NS control, and it showed a similar result in circulating DHBsAg. When samples of
      liver DNA were processed for hybridization, a little difference in the DHBV DNA
      replication was noted between ducks receiving CH925, IL-2 + IL-6 or NS placebo.
      It is suggested that CH925 might be a potential remedy in HBV infection
      treatment.

PMID- 8745581
TI  - Changes of plasma dynorphin levels before and after percutaneous balloon mitral
      commissurotomy in patients with mitral stenosis.
AB  - Plasma dynorphin A1-13 levels were measured in 33 patients with mitral stenosis
      before and after percutaneous balloon mitral commissurotomy (PBMC). The results
      show that the basal levels of plasma dynorphin in blood from the antecubital vein
      in the patients were significantly higher than those in 31 healthy control
      subjects. The increase in circulating dynorphin closely correlated with the
      functional cardiac status and the presence of atrial fibrillation. Ten to fifteen
      minutes after PBMC, plasma dynorphin levels in blood from the femoral vein
      increased significantly. Seventy-two hours after the procedure, the levels of
      plasma dynorphin in blood from the antecubital vein had decreased significantly,
      but they did not decrease to the normal range. Plasma dynorphin levels in blood
      from the femoral vein were positively correlated with the mean left atrial
      pressure and the mean right atrial pressure before the first balloon inflation.
      Plasma dynorphin levels in blood from the antecubital vein were positively
      correlated with the heart rate and the mean transmitral pressure gradient, and
      negatively with the mitral valve area before and 72 hours after PBMC.

PMID- 8745582
TI  - Immunoglobulin depositions in peripheral nerves in polymyositis.
AB  - An immunocytochemical study was performed in 6 peripheral nerve specimens from 6
      cases of polymyositis. The results revealed that depositions of IgG, IgM, IgA and
      C3 were found in the epineurium, perineurium and the walls of capillaries. These
      findings demonstrated that depositions of immunoglobulins and the complement
      mediated immunoreaction may play an important role in pathogenesis of
      polymyositis with peripheral nerve involvements.

PMID- 8745583
TI  - Presence of antilamin antibodies in sera of patients with systemic lupus
      erythematosus.
AB  - In this study, we characterized specifically-stained sera from patients with
      systemic lupus erythematosus (SLE) which had been shown to display the
      homogeneous or peripheral region of nuclei by indirect immunofluorescence (IIF).
      By western blotting, we demonstrated that in some cases there was a correlation
      between the peripheral or homogenous. IIF staining of nuclei by sera from
      patients with SLE and the presence of autoantibodies to lamins. Here we first
      report the presence of 2.2% anti-lamin autoantibodies in the sera among the 174
      patients with SLE in China.

PMID- 8745584
TI  - Biomechanical study on unilateral single-plane external fixer.
AB  - Six tibias removed from 30-40 years old males, who died in an accident for in
      less than 12 hours, were osteotomized at one-third supra-medium segment. They
      were fixed by an unilateral adjustable external fixer (UAEF), to be used as a
      model of external fixation of tibial fracture (MEFTF). The compression, tension,
      torsion, antero-posterior and lateral bending strength, and the strength for
      vertically extracting the pins from the tibia were determined in the MEFTF.
      Within a certain range of load, the correlation of strain to stress was basically
      a linear relationship. These data provide a theoretical basis of biomechanics for
      the improvement of UAEF and for early exercises of fracture patients, such as
      extend-bending of the joint, raising the limb and walking with a walking stick.

PMID- 8745585
TI  - Factors affecting removal and prognosis of thymic tumors.
AB  - One hundred and ten cases of thymic tumors were intervened surgically, including
      92 thymoma, 8 thymic carcinoid, and 10 thymic carcinoma. In this series, 50.9% of
      the cases were complicated with various syndromes, 44.5% with myasthenia gravis
      (MG). Resection rate was correlated with the size and invasion of the tumor.
      There was significant difference in resection rate among thymoma, thymic
      carcinoid and thymic carcinoma. The degree of invasion undoubtedly influenced on
      resection. The 3-, 5- and 10- year survival rate of the thymoma were 82.7%, 68.1%
      and 40.0%, respectively. The prognosis depended on the pathological
      classification and the severity of the neighbouring invasion, but MG had no
      significant effect on prognosis. Recurrence and metastasis of the tumor were the
      main cause of late death.

PMID- 8745586
TI  - Abnormal left ventricular systolic and diastolic functional response to isometric
      exercise in idiopathic dilated cardiomyopathy: beneficial effect of captopril.
AB  - In 19 patients with idiopathic dilated cardiomyopathy and symptoms of congestive
      heart failure, left ventricular (LV) systolic performance and diastolic velocity
      profiles were assessed by two- dimensional echocardiography and pulsed wave
      Doppler at rest and during handgrip exercise before and ninety minutes after
      administration of captopril (mean dose 25 +/- 12mg; range 12.5-50mg). Although
      heart rate and blood pressure increased similarly during handgrip exercise before
      and after captopril treatment, both were lower with handgrip exercise during
      captopril treatment. The results from this study indicated that acute
      angiotension converting enzyme inhibition with captopril reduces preload and
      afterload and ameliorates handgrip exercise-induced LV systolic and diastolic
      filling dysfunction in patients with congestive heart failure secondary to
      idiopathic dilated cardiomyopathy.

PMID- 8745587
TI  - The effect of anisodamine on cerebral resuscitation of rats in acute cerebral
      ischemia from cardiac arrest.
AB  - In order to investigate the mechanisms of acute cerebral ischemia, and to look
      for effective drugs on cerebral resuscitation, we made a model of acute complete
      global brain ischemia, reperfusion and resuscitation on rats according to
      Garavilla's method. Our results showed that the event of cerebral ischemia and
      reperfusion injury could result in the increase of total brain calcium content,
      and anisodamine has the same reducing brain calcium contents as diltiazem's,
      while improving neurological outcome and alleviating injury to neurons.

PMID- 8745588
TI  - [Natural history of hepatitis C virus infection].
AB  - Infection by hepatitis C virus (HCV) generally induces an asymptomatic acute
      hepatitis. HCV infection becomes chronic in about 80% of cases. Chronic HCV
      infection is asymptomatic with persistent viremia and normal liver tests in a
      minority of the subjects. Chronic HCV infection is associated with chronic
      hepatitis with increased serum transaminases levels in the majority of the
      subjects. Among the patients with chronic hepatitis, the majority have minimal
      lesions; about 20% have a more severe disease and will develop after 5 to 20
      years cirrhosis. In patients with cirrhosis, the incidence of hepatocellular
      carcinoma is high (around 5% per year). The factors influencing the evolution of
      HCV infection are not know. Alcohol is certainly an important factor. Virus
      related factors, such as genotype and level of replication, might also be
      important factors.

PMID- 8745589
TI  - [Hepatitis C virus infection. Epidemiology].
AB  - Hepatitis C virus (HCV) transmission is parenteral in 60 to 70% of cases, related
      either to blood transfusion or to intravenous drug use. Minor routes of infection
      have also been identified: sexual transmission, intrafamilial transmission,
      mother-to-infant transmission. In 30 to 40% of cases, no obvious risk factor for
      HCV contamination can be identified. Subjects at risk for HCV infection are
      patients who received transfusions of blood or blood products, hemophiliacs,
      patients under renal dialysis, patients who underwent organ transplantation,
      intravenous drug users and, to a lesser extent, healthcare workers. HCV is
      present everywhere in the world. The prevalence of HCV markers varies from 0.5%
      in Scandinavia or Switzerland to more than 5% in some developing countries. This
      prevalence is about 1% in France. The study of HCV genotypes shows that their
      distribution varies according to geographical localization and that some
      genotypes are associated with special routes of contamination.

PMID- 8745590
TI  - [Hepatitis C virus. Virological diagnosis].
AB  - Hepatitis C virus (HCV) has been discovered in 1989 and is probably the most
      common cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma. HCV is
      a single-stranded, positive-sense RNA virus, 9.4 kilobases in length. The genetic
      organisation and the properties of viral proteins have been characterized. At
      least 50 HCV genotypes or subtypes have been identified. Genotypes 1, 2 and 3 are
      the most commonly observed in patients from Europe and USA. Genotype 1 is more
      resistant to interferon treatment. The hypervariability of HCV is responsible,
      within a single patient, of the existence of a spectrum of very closely-related
      genomes reffered as quasispecies that may be a mechanism of escape from the
      immune response and may explain chronicity. Virological diagnosis of HCV
      infection is based on the detection of anti-HCV antibodies by ELISA. In some
      cases (acute hepatitis, problems in the interpretation of ELISA tests, or in
      immunosuppressed patients), it is necessary to search for HCV RNA using genomic
      amplification or amplification of hybridization. These technics can also be
      useful to predict the response to interferon, as it has been demonstrated that
      patients with low viremia are better responders than others. HCV RNA detection or
      quantification could also be useful to follow the efficiency of anti-viral drugs.

PMID- 8745591
TI  - Pathophysiology of hepatitis C virus infection.
AB  - Any physiopathological hypothesis of HCV infection must explain at least some of
      the most characteristic features of this infection, namely: 1) persistent
      infection in the majority of exposed individuals, associated with a wide spectrum
      of histological damages and fluctuating biochemical expression; 2) low tendency
      towards spontaneous recovery; 3) high tendency to progress to cirrhosis; 4) high
      prevalence of autoimmune phenomenons; 5) very weak or absent immunity to
      reinfection. A model is given taking into account the nature of the HCV genome,
      the immune response of the host to the infection and the potential mechanisms(s)
      involved in viral persistence.

PMID- 8745592
TI  - [Histopathology of viral hepatitis C].
AB  - In patients with C virus, liver biopsy is an essential examination for diagnosis
      of chronic hepatitis. This examination evaluates the two basic lesions of the
      disease: aggressivity and fibrosis. During antiviral treatment, only liver biopsy
      is able to give precise details about liver lesions and no reliable serum test is
      yet available for the follow-up. Molecular biology methods applied to liver
      sections for viral genome detection will be of great interest for follow up and
      pathophysiology of the chronic disease. These sensitive techniques will supply
      absence of any pathognomonic histological feature associated with C virus in
      liver tissue.

PMID- 8745593
TI  - [Extrahepatic manifestations related to hepatitis C virus].
AB  - The hepatitis C virus infects mononuclear cells and, like other viruses, can be
      responsible for immune disorders. The immune abnormalities described in the
      course of hepatitis C consist of nonspecific immunological disorders
      (cryoglobulinaemia, autoimmune disorders, generally associated with the presence
      of organ-specific or nonspecific autoantibodies). The association between mixed
      cryoglobulinaemia and hepatitis C has been clearly established, as 50% of
      patients with essential cryoglobulinaemia suffer from hepatitis C and 50% of
      patients with hepatitis C suffer from cryoglobulinaemia. The relationships
      between hepatitis C and other autoimmune disorders is less clear. The association
      between hepatitis C and anti-smooth muscle and antinuclear antibodies has been
      emphasized. However, the frequency of these autoantibodies in hepatitis C does
      not appear to be significantly different from than observed in other forms of
      viral hepatitis, especially hepatitis B. However, patients with hepatitis C have
      a higher incidence of anti-LKM1 antibodies than patients with other forms of
      viral or alcoholic liver disease. A high prevalence of hepatitis C viral
      infection has also been reported in Sjogren's syndrome, lichen planus and thyroid
      disorders. However, the relationship between viral infection and these immune
      disorders has not been demonstrated by large-scale epidemiological surveys or by
      basic virological studies. The development or exacerbation of immune disorders in
      patients treated by interferon has also been clearly demonstrated, which means
      that an autoimmune assessment, especially looking for anti-tissue and anti
      thyroid antibodies, should be performed before prescribing interferon.

PMID- 8745594
TI  - [Treatment of hepatitis C].
AB  - The treatment of hepatitis C virus (HCV) infections is essentially known for
      chronic hepatitis C and is mainly restricted to interferon alpha. Initial trials
      have indicated that around 50% of the patients with chronic hepatitis C respond
      to alpha interferon (administered at 3 MU, thrice weekly, during 6 months) by
      normalizing alanine aminotransferase at the end of therapy, although 25% were
      found to relapse after therapy. Normalization of biochemical tests is associated
      with an improvement in liver histological features and with decrease or loss of
      HCV from serum and liver. Response to therapy is influenced by both duration and
      dose levels of the treatment. Following studies which showed that higher doses
      and longer duration were more effective than the current recommendations of 3MU
      thrice weekly for 6 months have recently conducted to the recent recommendation
      of a 12 month course of therapy using 3 MU. The outcome of therapy was also shown
      to be negatively influenced by longer duration of disease and presence of
      cirrhosis. More recently, the critical role of virological markers has been
      emphasized with a lower rate of response in patients infected with the genotype 1
      b and a high viral load. However, these factors do not certainly predict for an
      individual patient the quality of the response. Therapeutical goals are: to
      precisely define pre-treatment scores of response able to give each individual
      patient the optimal treatment regimen, non responders to interferon alpha and
      patients with a transient benefit of therapy. Thus, development of new treatments
      appears critical among which those with other interferons and above all the
      bitherapy using ribavirin and interferon alpha which may have a marked increase
      in efficacy in comparison with interferon alpha used as monotherapy.

PMID- 8745595
TI  - [Transfusion and hepatitis C].
AB  - Hepatitis C has been a major transfusionnal risk until the beginning of the 90's,
      since it accounted for more than 90% of non-A, non-B hepatitis, 5% to 10% of
      infected surgical recipients and up to 50% of multitransfused patients,
      alltogether 100,000 to 400,000 blood components recipients in France. The decline
      in incidence was based principally on sequential introduction of donor testing,
      starting with surrogate markers in 1988 (transaminase ALT and antibody anti-core
      HBc), followed since 1990 by specific assays (anti-hepatitis C virus antibodies)
      and on blood donor selection. Two risk factors have been identified in donors,
      intravenous drug use and previous transfusion. The risk of transmission was
      estimated, after screening by first generation tests at 1 per 1670 units
      transfused. After second generation testing, the risk ranged from 1 in 2000 to 1
      in 6000 units transfused, corresponding to a reduction of more than 90%. The
      estimation of the residual risk (mean: 1/100,000 donations in USA), principally
      due to incidence in regular donor required mathematical calculation. The new
      "hemovigilance" system in France with mandatory notification of all
      posttransfusionnal incidents and infections will contribute to evaluate and to
      prevent residual cases. However, further studies are necessary to precise other
      risk factors in donors, as well as the role of nosocomial infections in recent
      cases, and possibly the role of additional agents such as GB viruses in post
      transfusionnal hepatitis.

PMID- 8745596
TI  - [Hepatitis C virus infection in hemodialysis].
AB  - The surveillance of HCV infections is now a must in the clinical management of
      hemodialysis patients. The natural history of HCV has shown acute hepatitis to be
      a constant feature although rarely symptomatic. Progression to chronicity occurs
      in 90% of the cases with detectable viremia in 80% of the cases. The long-term
      impact of the liver disease in chronic hemodialyzed patients remains to be
      defined. HCV is responsible for more than 90% of the non-A, non-B hepatitis case
      diagnosed among hemodialyzed patients. The transmission is either transfusional
      or nosocomial. Following recent transfusion safety regulations, the nosocomial
      risk became the predominant residual risk. Thus, all efforts should target HCV
      eradication. In the absence of specific prophylaxis, this can only be achieved by
      enforcement of very stringent precautions.

PMID- 8745597
TI  - [Imaging of the lumbar spine after diskectomy].
AB  - The radiological investigation of persistent or recurrent sciatica after lumbar
      diskectomy essentially consists of demonstrating recurrent disk herniation.
      Comparison between plain and contrast enhanced CT or MR examinations at the level
      of the diskectomy is the main step of the radiological survey. The meanings of
      the various radiological findings are discussed. Other lesions that may induce
      persistent sciatica after lumbar diskectomy include degenerative narrowing of the
      lateral recess, spinal instability, stress fracture of the remaining neural arch,
      pseudo-meningomyelocele after laminectomy.

PMID- 8745598
TI  - [Vertebral localizations of Paget disease].
AB  - Paget's disease, often an incidental finding, sometimes presents in the form of
      pain or signs of complications, such as spinal cord compression, malignant
      transformation or fissures. The diagnosis is established by laboratory tests, but
      essentially by radiological findings, based on three basic criteria: cortical
      thickening, loss of cortico-cancellous differentiation and enlargement of the
      bone, which deformity is a later sign. The diagnosis can usually be made on plain
      x-rays, but CT is useful in the case of early, difficult or unusual lesions and
      complications. CT can reveal mouth-eaten, vacuolar, network, clumped or mixed,
      fibrillary or ivory images. MRI is a last resort examination. Angioma, metastases
      and ivory vertebrae are the main differential diagnoses.

PMID- 8745599
TI  - [Computed tomography of the sacroiliac joints].

PMID- 8745600
TI  - [Vertebral vacuum phenomena].
AB  - The spinal vacuum phenomenon is a collection of gas within the disk space, the
      vertebral body, the apophyseal joint or the spinal canal. The intradiscal vacuum
      phenomenon is frequently observed in degenerative disk disease and crystal
      induced diskopathy. This has obvious significance to the radiologist, who, on
      observing a narrowed disk space or collapsed vertebral body, might otherwise
      consider infectious or neoplastic spondylitis, a likely possibility. The presence
      of vacuum phenomenon militates against the diagnosis of infection or tumor.

PMID- 8745601
TI  - [Cortisone injection into the sacroiliac joint].
AB  - Corticosteroid injection of the sacroiliac joint can be proposed in inflammatory,
      or less frequently, in degenerative sacroiliac arthropathies. Significant pain
      relief is not only rapid and lasting, but also frequent (about 80% in
      seronegative spondylarthropathy).

PMID- 8745602
TI  - [Current imaging of spondylolisthesis by isthmic lysis].
AB  - Unilateral spondylolytic spondylolisthesis may cause lateral tilt of the
      overlying spinous processes towards the normal isthmus on PA views. Bilateral
      spondylolytic spondylolisthesis is generally located at the L5-S1 level. The
      vertebral shift is usually moderate. Instability at the level of
      spondylolisthesis may be demonstrated by stress lateral views but is uneasy to
      quantify. In case of sciatica associated to spondylolisthesis, foraminal stenosis
      is probably the most frequent cause but foraminal compression of the spinal
      ganglion is difficult to assess on imaging.

PMID- 8745603
TI  - [Lumbar puncture with a fine needle].
AB  - 26-Gauge fine needle for lumbar puncture allows lower rate and intensity of post
      lumbar puncture syndrome. This technique drammatically decreases discomfort in
      patients who undergo myelography and helps in keeping this imaging modality
      indicated when necessary.

PMID- 8745604
TI  - [Extraligamentous lumbar intervertebral disk displacement].
AB  - The preoperative assessment of sciatica secondary to a herniated intervertebral
      disk has been radically changed over recent years due to the development of
      percutaneous treatment techniques which now offer an alternative to surgery.
      After recalling the terminology used for the position of a herniated lumbar disk
      in relation to the posterior common vertebral ligament (subligamentous or
      transligamentous hernia) and to describe whether or not the hernia is detached
      from the original disk (excluded or non-excluded hernia), the authors review the
      current state of the art of imaging for each type of herniated lumbar
      intervertebral disk.

PMID- 8745605
TI  - [Radioguided injection of the lumbar and the first sacral intervertebral
      foramina].
AB  - Lumbar foraminal injection under fluoroscopic guidance is indicated either for a
      diagnostic purpose to determine which nerve root is painful or for a selective
      steroid injection. Lumbar foraminal approach is based on that of the
      posterolateral extradural diskography. Selective puncture of the first sacral
      foramen under fluoroscopic guidance may be indicated for the treatment of sacral
      symptomatic meningeal cysts, a very unfrequent lesion.

PMID- 8745606
TI  - [Degenerative vertebral dislocation].
AB  - Degenerative vertebral dislocations (laterolisthesis) are responsible for
      progressive transverse intervertebral shift. These changes appear like a
      translation of the lateral edge of a vertebra compared to that of the underlying
      vertebra and are easily diagnosed. Vertebral dislocations can be secondary to
      active lumbar scoliosis or unilateral or asymmetrical degenerative
      spondylolisthesis. In every case, the appearance of laterolisthesis is reflected
      by the onset or aggravation of scoliosis which may become self-perpetuating. This
      lesion is secondary to osteoarthritic disruption of the integrity of the
      intervertebral disk and ligaments. Open and closed patterns have been described
      depending on the side of the associated disk opening. The onset of a rotatory
      dislocation reflects the progressive evolution of the deformity, which may
      require medical treatment, or surgical reduction and fixation by vertebral
      arthrodesis.

PMID- 8745607
TI  - [For a better management of prevention in cardiology consultation].

PMID- 8745608
TI  - [Coronary angioplasty in cardiac transplantation].
AB  - Coronary artery disease is a common complication of cardiac transplantation
      threatening long-term survival and its management is not well defined.
      Percutaneous transluminal coronary angioplasty has been proposed as a palliative
      and exceptional technique in some patients with limited lesions. Of 145 patients
      undergoing cardiac transplantation between April 1983 and January 1994, 7
      underwent 10 coronary angioplasty procedures. The majority was performed in
      asymptomatic patients, 4 for angigraphic abnormalities alone and 3 for documented
      painless ischaemia. Primary angiographic success was obtained in 90% (9 out of
      10) of lesions. Complication included one acute occlusion and one arteriovenous
      fistula. Three patients died, 1, 8 and 10 months after angioplasty. After an
      average of 24 months' follow-up, 3 (out of 7) patients had no cardiac events
      (myocardial infarction, second angioplasty, second transplantation or death). A
      multicentre prospective controlled trial is necessary to assess the impact of
      this procedure on graft and patient survival.

PMID- 8745609
TI  - [Is percutaneous transluminal coronary angioplasty in chronic total coronary
      occlusion justified? Long term results in a series of 201 patients].
AB  - Percutaneous transluminal coronary angioplasty of chronic total coronary
      occlusions has a low primary success rate and is associated with a high
      percentage of restenosis. The aim of this retrospective study was to assess the
      long-term benefits of these procedures. In a series of 201 patients with 203
      chronic total occlusions, the technical success rate was 51%, the clinical
      success rate was 46% with 3% of major complications. The only factor associated
      with a favourable outcome was the presumed duration of the occlusion. The
      clinical follow-up period was established at 6 years. The result of the initial
      procedure was used to establish two groups of patients: group I, clinical
      success, and group II, clinical failure. Patients in group I had a probability of
      survival greater than that of those in group II (97 vs 92%; p < 0.05); survival
      without coronary bypass surgery was also significantly better (89 vs 74%; p <
      0.003). On the other hand, the probability without angioplasty was less in group
      I (70 vs 77%; p < 0.01), the result of a high restenosis rate (48%). A Cox
      analysis identified clinical success of angioplasty as a good prognostic factor
      for survival. Moreover, the clinical status at long-term was significantly better
      in patients in group I. These results indicate that in patients with chronic
      total coronary occlusions, the success of angioplasty has a favourable effect on
      long-term outcome both in terms of survival and in quality of life. They must be
      interpreted in the light of the limitations inherent in a retrospective study and
      should be confirmed by prospective trials.

PMID- 8745610
TI  - [Coronary artery disease in octogenarians: contribution of coronary angiography
      and evaluation of therapeutic possibilities].
AB  - An increasing number of octogenarians is being referred for coronary angiography
      with a view to myocardial revascularisation. Based on a retrospective study of
      168 octogenarians undergoing coronary angiography between January 1987 and
      December 1992, the authors reviewed the indications, the risks and therapeutic
      decisions taken in those patients with significant coronary artery disease. The
      population studied had acute myocardial ischaemia in 88.7% of cases, a low
      incidence of previous myocardial infarction and severe extracardiac pathology.
      Significant coronary lesions were observed in 90% of patients (151) with multiple
      vessel diseases in 57.8% of cases. The mortality attributed to coronary
      angioplasty was 0.59% (1 case) and the morbidity was 4.7%. The number of disease
      vessels did not influence the decision as 75.5% of single vessel, 75% of double
      vessel and 77.3% of triple vessel disease patients were referred for coronary
      surgery or angioplasty. Of the patients undergoing a revascularisation procedure
      (n = 108), those referred for surgery (n = 22) had more severe coronary disease
      than those referred for angioplasty (p < 0.05). The hospital mortality was high
      about 8%, irrespective of the therapeutic decision. The 3 year actuarial survival
      was 70% in the group undergoing myocardial revascularisation (whether by
      angioplasty or coronary surgery) and 53.6% in subjects treated medically. These
      results show that coronary angiography in a selected elderly population is
      possible although the mortality and morbidity should not be underestimated. A
      high proportion of these patients (72%) is referred for myocardial
      revascularisation.

PMID- 8745612
TI  - [On the use of the gastroepiploic artery in myocardial revascularization].
AB  - Between 1985 and 1992, the gastroepiploic artery was used for coronary bypass
      surgery in 80 consecutive patients. Revascularisation was totally arterial in
      62.5% of cases, the gastroepiploic being associated with single or double
      internal mammary artery grafts. The gastroepiploic graft was used to
      revascularise the inferior myocardial regions. The postoperative morbidity was
      essentially due to respiratory complications: 6 patients had objective pulmonary
      complications and 11 patients had relative transient postoperative hypoxia. The
      early gastrointestinal complications were related to ulceration (5 patients)
      complicated by haemorrhage in 2 patients. This morbidity was responsible for a
      significant increase in the period of intensive care. The hospital mortality was
      6.2%, observed mainly in the first third of the author's experience and in
      patients with preoperative poor prognostic factors. These relatively high
      morbidity and mortality rates have led to a cautious use of the right
      gastroepiploic artery for coronary bypass surgery in patients over 70 years of
      age, in those with unstable angina operated as an emergency and in those with
      associated pathology, especially respiratory problems. The choice of a complex
      surgical option should not be synonimous with an increased postoperative
      mortality.

PMID- 8745611
TI  - [Atrial insertion of accessory pathways in permanent reciprocating junctional
      tachycardia].
AB  - Permanent reciprocating junctional tachycardia (PRJT) is an uncommon type of
      Tachycardia, usually associated with a retrogradely conducting accessory pathway
      situated near to the ostium of the coronary sinus. This study reports the
      localisation of the site of atrial insertion of the accessory pathway, confirmed
      by the efficacy of intracardiac catheter ablation. Five patients (4 men), aged 14
      to 45, experienced PRTJT at rates of 120 to 150/mn over a period of 2 to 15
      years. 4 patients were normal, expected in 2 patients in whom they were 16 and
      20%. One of these suffered a thromboembolic complication after pharmacological
      interruption of the tachycardia. The presence of an accessory pathway with
      decremential retrograde conduction was confirmed in all cases. Catheter ablation
      was successful in the medio-septal (2 cases), posteroseptal (1 case), lateral (1
      case) and anteroseptal (1 case) regions. Six to 30 applications of 20 to 30 watts
      of radiofrequency energy were used in the 5 cases. In one case (right lateral
      accessory pathway), a fulguration procedure was necessary with a cathodic shock
      of 160 Joules. The AV conduction was preserved and retrograde conduction was
      normalised in all cases. All patients remained asymptomatic for a period of 10 to
      43 months without antiarrhythmic therapy. The ejection fractions of the two
      patients with left ventricular dysfunction returned to normal. The authors
      conclude that the accessory pathways of PRJT may be situated in different regions
      of the right atrium. The efficacy of catheter ablation was 100 % in this form of
      tachycardia.

PMID- 8745613
TI  - [Does temperature in extracorporeal circulation affect neutrophil-endothelium
      interactions?].
AB  - The increasing interest in "warm" aerobic cardioplegia requires a critical
      reevaluation of the systemic effects of the associated normothermic
      cardiopulmonary bypass (CPB). As activated neutrophils seem to be essential
      mediators of the inflammatory response to CPB via the cytotoxicity of the
      products that are released during their adhesion to endothelial cells, the
      authors undertook a study of the influence of temperature on the interaction
      between the neutrophils and the endothelium in 95 patients undergoing warm (31
      33.5 degrees C, n = 49) and cold (26-27 degrees C, n = 46) CPB surgery. Blood
      sampling was performed before, during and after CPB. The following markers of
      neutrophil-endocardium interaction were analysed: complement activation (C3a),
      cytokine production (tumor necrosis factor alpha, interleukines 1, 6 and 8, and
      interleukin-1 receptor antagonist); endothelial expression of cytokine-dependent
      [intercellular adhesion molecule (ICAM)] and cytokine-independent (P-selectin)
      adhesion molecules (P-selectin); expression of cytokine molecules on the surface
      of polynuclear neutrophils (CD11a, CD11b, CD11c); and finally, endothelial
      adhesion and transendothelial migration of neutrophils (interleukin 8 and
      elastase). The results showed that, irrespective of temperature, CPB was
      associated with changes strongly suggestive of phenomena of transendothelial
      adhesion and migration. Moreover, normothermia increased the intensity of the
      inflammatory response as shown by increased cytokine production, earlier
      expression of neutrophil adhesion molecules and increased elastase production.

PMID- 8745614
TI  - [Relation between plasma renin level and antihypertensive response to
      nicardipine].
AB  - The antihypertensive efficacy of calcium antagonists could depend on the
      concentration of circulating renin. To investigate this hypothesis, 102
      hypertensive men or women were included in this study. After an initial 2 week
      placebo period, the patients were administered slow-release nicardipine, 50 mg
      twice a day for twelve weeks. The blood pressures were measured with a mercury
      sphygmomanometer at inclusion (S2) and after 12 weeks of treatment (S14), in
      addition to home automeasure during the week before inclusion and the two weeks
      preceding the final visit. The plasma renin activity (RA) was measured at S2 and
      S14. Its value at inclusion was used to differentiate patients with low renin (<
      or = 11 ng/l) from those with normal (> 11 < or = 17 ng/l) or high renin activity
      (> 17 ng/l). The blood pressure measured by sphygmomanometer or automeasure was
      significantly lower at the end of the active treatment period (SBP: -8 mmHg; DBP:
      -9.5 mmHg; and SBP: -5.8 mmHg; DBP: -5.7 mmHg respectively); the reduction in
      blood pressure was significantly higher in the group with low RA than in the
      group with high RA. The reductions in SBP measured in the morning and evening and
      in DBP measured in the morning were significantly greater in the group with low
      RA than in the group with high RA. The reduction of SBP measured in the morning
      at midday, and in the evening was correlated to the basal value of RA. Mild side
      effects were observed in 20 patients leading to the interruption of treatment in
      11 cases because of headache. The best antihypertensive response is observed in
      patients with low plasma RA. This could explain the good response to calcium
      antagonists usually observed in elderly hypertensives.

PMID- 8745615
TI  - [Percutaneous closure of patent ductus arteriosus: results and costs compared to
      surgical closure].
AB  - The comparison of the clinical results and costs of the two methods of closure of
      patient ductus arteriosus was undertaken in two comparable groups of 40 patients
      treated in the same period in the same hospital. After transcatheter closure
      there was a 9% residual shunt rate at 3 years, the 2 patients with a residual
      continuous murmur being operated secondarily. The only complication was severe
      haemolysis which regressed after transcatheter ablation of the prosthesis. After
      surgical closure, there were no residual shunt. Some postoperative complications
      were observed in 20% of cases, usually benign (ventilatory problems, dysphonia or
      urinary infection), but occasionally more serious (peroperative lesion of the
      pulmonary artery). Morbidity, inherent to the technique of closure, was very
      different and much less in catheter closure. The average cost (daily cost x
      average length of hospital stay) was much less with transcatheter closure 38,558
      francs versus 11,240 francs. On the other hand, the direct cost of transcatheter
      closure was greater than that of surgery: 32,798 francs versus 20,903 francs, the
      difference being related to the actual price of the prosthesis. The authors
      conclude that the 3 year results of transcatheter closure of patent ductus
      arterious make this technique a reasonable therapeutic alternative to surgery.
      From the safety point of view, the two techniques are comparable bu patient
      confort is greater with transcatheter closure for an increase in cost of the
      initial procedure which should decrease in relation to the types and prices of
      the prosthesis used.

PMID- 8745616
TI  - [A clinical study of cardiac manifestations related to acquired immunodeficiency
      syndrome (AIDS) in Kinsaha].
AB  - A prospective study was performed from march 31 st 1991 to september 30th 1992 on
      cardiac involvement in course of AIDS. Clinical, electric, sonographic and
      radiologic aspects were analysed within 83 patients of the study. In this cohort,
      45.8% of patients had shown a cardiac involvement through all strates and
      respectively: a pericarditis with effusion in 24 patients (27.7%), a dilated
      cardiomyopathy in 14 patients (16.9%) and infective endocarditis in 1 patient
      (1.2%). Dispncea between classes II and IV of NYHA was the main complaint.
      Tachycardia, silent cardiac sounds and congestive heart failure were the
      prominent features of the clinical examination of the cohort. Because of the
      likely high prevalence of cardiac manifestations in course of AIDS, clinicians
      and researchers have to pay attention to this situation.

PMID- 8745617
TI  - [Multi-instrumental revascularization adjusted to coronary lesions (MIRACLE).
      Current role of new technologies].
AB  - Several new techniques have been developed to get round the limitations of
      conventional coronary angioplasty. Most entail ablation of the atheromatous
      plaques by mechanical (atherectomy) or photochemical (laser excimer) means,
      whilst others (stents) shore up the vascular walls. Their use with conventional
      coronary balloon angioplasty optimises the results of treatment of complex
      lesions. This report describes the authors' experience in 1,266 patients (1,668
      lesions) treated between January 1992 to December 1993. The new techniques were
      used in 33% of patients and 30% of lesions (rotational) atherectomy: 20%; stents:
      5%; directional atherectomy: 3%; laser excimer: 2%) because of the defavourable
      angiographic characteristics of the lesions (eccentricity, calcification,
      bifurcation, length, chronic total occlusion, thrombosis, ostial stenosis,
      ulceration, saphenous vein graft). The primary success rate was 91% in the whole
      group (94 to 97% for the patients treated by the new techniques). The global
      major complication rate was 1.7%. The multi-instrumental revascularization
      adjusted to the coronary lesions (MIRACLE) gives a high primary success rate in
      patients with coronary lesions difficult to treat by conventional angioplasty.
      Randomised trials will be necessary to determine the precise indications of each
      technique with respect to the morphological characteristics of each lesion.

PMID- 8745619
TI  - [Biophysical basis and cardiac lesions caused by different techniques of cardiac
      arrhythmia ablation].
AB  - Although pharmacological treatment of cardiac arrhythmias remains by far the most
      widely used, non-pharmacological methods are acquiring an increasing role in
      their management. This update concerns ablation techniques of the normal and
      accessory pathways and arrhythmogenic foci and the biophysical basis and the
      mechanisms of the lesions. A number of energy sources and ablation catheters were
      used to treat the arrhythmias. Continuous electrical current of fulguration was
      the first energy source to be used. This required a classical external
      defibrillator connected to an "active" electrode at the tip of a catheter and to
      a larger skin electrode ("passive"). The mechanism of ablation in fulguration
      uses the thermal energy produced at the tip of the electrode. Other mechanisms
      such as the creation of an electrical field and a sudden increase in pressure
      ("barotrauma") also play a role. The lesions produced are deep and proportional
      to the energy, size and form of the electrodes and the form of the electrical
      current. The radiofrequency current has replaced fulguration in most indications.
      It uses alternate current with frequencies usually ranging between 350 and 700
      kHz delivered between a wide distal electrode (7 F, 4 mm) tip and a skin
      electrode. They are on small and characterised by the destruction of the cellular
      architecture by coagulation or dessication related to the hyperthermia. The size
      of the lesions depends on the amount of energy delivered, the size of electrode
      and the quality of contact with the cardiac tissues. Other types of ablation are
      under study but have not yet been shown to be superior to radiofrequency energy.

PMID- 8745618
TI  - [Continuous ambulatory measurement of left ventricular function by an isotopic
      method].
AB  - Ambulatory cardiac radionuclide monitoring is a relatively new technique of non
      invasive assessment of left ventricular function. This technique, which uses a
      portable gamma-ray detector, enables continuous recording over a number of hours
      of global left ventricular ejection fraction after red cell labelling with
      technetium. The detector is placed in contact with the skin over the apical
      region in a 45 degrees left anterior oblique view. Adequate collimation enables
      the variations in left ventricular volume during the cardiac cycle to be
      quantified and the ejection fraction to be deduced without having to generate an
      image. The authors review this method and describe the different available
      systems. They may be classified in two groups as to whether the technique is
      limited to continuous bed-side monitoring or if used for ambulatory monitoring
      (the only commercially available model being the Vest). Validation studies and
      trials in normal subjects are envisaged. The information acquired by this new
      method is analysed in the different clinical fields: post-infarction, stable
      angina, asymptomatic coronary artery disease, hypertension. The role of this new
      technique in the investigation of coronary artery disease is discussed with
      respect to other non-invasive techniques. The limitations of the technique and
      the material are reviewed and possible future developments are described.

PMID- 8745620
TI  - [Apropos of a government memorandum of 29 December 1994 and a 16 March 1995
      ordinance relative to the use of disposable sterile medical equipment].

PMID- 8745621
TI  - [Giant negative T waves in idiopathic apical diverticulum of the left ventricle
      in adults].
AB  - Left ventricular diverticula, congenital or acquired, with normal coronary
      arteries are rare. Apical diverticula are exceptionally rare in the adult. The
      authors present the clinical, paraclinical, anatomopathological pre- and
      postoperative data in a case of apical diverticulum of the left ventricle
      presenting with giant negative T waves. The differential diagnosis of these
      electrocardiographic changes is discussed, in particular apical cardiomyopathy,
      especially as the two conditions may be associated.

PMID- 8745622
TI  - [Pulmonary thrombectomy in a patient with antiphospholipid syndrome].
AB  - Chronic pulmonary embolism may occur in the antiphospholipid syndrome.
      Antiphospholipid antibodies including the lupus anticoagulant and anticardiolipin
      should therefore be searched for systematically in these patients. Blood clotting
      (lupus anticoagulant) and immunological (anticardiolipin) investigations are
      complementary; their positivity may be dissociated. If the thrombus is located in
      the proximal pulmonary artery, surgical thrombectomy is possible. Operative
      mortality ranges from 12.6% to 20%. The association of oral anticoagulants with
      low dose aspirin is indicated for the long term treatment of these patients. The
      role of steroid therapy is discussed. The authors report the case of a patient
      with antiphospholipid antibodies who successfully underwent surgical removal of a
      chronic pulmonary embolism.

PMID- 8745623
TI  - [Muscular involvement in HIV infection].
AB  - Skeletal muscle involvement may occur at all stages of HIV-infection and
      represents the first manifestation of the disease in some patients. We usually
      classify muscle involvement in HIV-infected patients in one of the following
      categories: (1) HIV-associated myopathy, a myopathy that meets the criteria for
      polymyositis in a majority of patients, and those for acquired nemaline myopathy
      in some; (2) zidovudine myopathy, a reversible mitochondrial myopathy; (3) the
      HIV-wasting syndrome and other AIDS-associated cachexias; (4) opportunistic
      infections and tumoral infiltrations of the skeletal muscle; (5) vasculitic
      processes and iron pigment deposits; (6) HIV-associated myasthenia gravis and (7)
      rhabdomyolysis. Immunohistology for major histocompatibility complex class I
      antigen and histochemical reaction for cytochrome c oxidase are helpful in
      correct classification of a myopathy as HIV polymyositis or zidovudine myopathy.

PMID- 8745624
TI  - [Molecular biology in cerebral gliomas: recent advances].
AB  - Meanwhile first gene therapy assays in cerebral gliomas are in progress, we
      present in this article a review of the major genetic aberrations reported to
      date in these tumors. The analysis of these alterations enabled, these last few
      years, significative advances in the understanding of the mechanisms involved in
      glioma tumorigenesis. It is now well recognized that tumors result from a
      multistep process requiring in particular proto-oncogenes activation and tumor
      suppressor genes inactivation. The different genes implicated in the development
      of gliomas, their place in the tumoral progression and their potential
      therapeutic relevance are detailed in this review. The continuation of the
      identification of glioma altered genes is essential to provide new diagnostic and
      pronostic markers, and specific targets for more efficient therapy.

PMID- 8745625
TI  - [Neurological applications of single photon emission tomoscintigraphy].
AB  - Brain single photon emission tomography is a functional imaging modality in
      constant evolution. Tracers belong to 4 categories; blood pool tracers, perfusion
      tracers, ligands of receptors, "metabolic" tracers. Examination conditions must
      be accurately described since they may cause specific cerebral activation. The
      interpretation must be done in comparison with a morphological examination (CT or
      NMR). Cerebrovascular diseases, temporal lobe epilepsy and dementia were the
      first domains of application. Now many studies concentrate on cerebral cognitive
      or pharmacological activation procedure before the tracer injection to capture an
      aspect of the brain functioning. It is mandatory to clearly state what is
      expected from the examination: an answer for a given patient and a specific
      question or a study of an homogeneous group of patients. In order to yield
      relevant results, such studies must rely on a rigorous methodology.

PMID- 8745626
TI  - [Cadasil--a new model for subcortical dementia].
AB  - We report 3 cases of Cadasil with dementia. In the 3 cases, the dementia had a
      subcortical and frontal presentation. It associated behavioural symptoms,
      amnesia, executive functions disturbances, bradyphrenia, slowing of information
      processing and frontal symptoms, without aphasia, apraxia or agnosia. One patient
      showed overt dementia before any focal neurological sign. Imaging of the brain
      was consistent with subcortical infarcts and leukoencephalopathy, without
      involvement of the cerebral cortex. We suggest that dementia and psychoaffective
      disturbances are major diagnostic criteria for Cadasil. This pathology is
      probably a good model for the neuropsychological study and the physiopathological
      analysis of the concept of subcortical dementia.

PMID- 8745627
TI  - [Frontal type dementia and amyotrophic lateral sclerosis. 3 cases with (HmPAO
      Tc99m) single-photon emission tomography study].
AB  - Three cases of rapid onset neuropsychological frontal dementia preceded the
      development of sporadic amyotrophic lateral sclerosis by 12 to 24 months. HmPAO
      Tc99m scintigraphy demonstrated hypoactivity in the cortex, predominantly in the
      frontal region. Three hypotheses are discussed: 1) coincidence between two
      degenerative diseases, Alzheimer's disease or Pick's disease and ALS; 2) an
      amyotrophic form of Creutzfeld Jakob disease; 3) pre-senile dementia associated
      with a motoneuron disease, a clinical pathology entity recently described by
      Mitzuyama.

PMID- 8745628
TI  - [Bilateral occlusion of the internal carotid arteries. Analysis of a series of 19
      patients].
AB  - The natural history of patients suffering from bilateral internal carotid
      occlusion is poorly known. We report a study of 19 patients presenting such a
      vascular condition as demonstrated by angiography. In all our cases, cardio
      vascular risk factors were frequently found. Smoking was particularly frequent
      and present in 18 patients (95%). Presenting neurological episodes included
      either transient ischemic attack (8/19) or stroke (9/19). Associated arterial
      lesions were diffusely distributed on the other cerebral vessels, frequently
      involving the extra-cranial part of the vertebral arteries. Collateral
      circulation feeding the intracranial carotid system mainly, or exclusively,
      originated from the vertebro-basilar system. Ischemic strokes were frequently
      detected by cerebral CT scan. They were located in the middle cerebral territory
      or at the junctions between 2 major cerebral arteries. A radiological aspect of
      cortical atrophy was noted in 9 patients among 19. Regional cerebral blood flow
      assessed by Xe133 inhalation was usually normal at rest (16/19), but
      hyporeactivity to acetazolamide was found in 10 patients among 19. The latter was
      more frequent in patients suffering from arterial hypertension or diabetes
      mellitus. Our results confirm that the patients suffering atheromatous bilateral
      occlusion of the internal carotid arteries may survive with minimal neurological
      deficits. Collateral circulation is mainly provided by the vertebro-basilar
      system allowing to frequently maintain normal cerebral blood flow at rest.

PMID- 8745629
TI  - [Does the ataxo-choreic form of DRPLA exist in Europe? Search of mutation in 120
      families].
AB  - Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant
      neurodegenerative disorder characterized by a degeneration of cerebellar and
      pallidal efferents, more frequent in Japan. Isolated cases are also encountered.
      Patients present with variable combination of signs including myoclonus, ataxia,
      epilepsy, choreoathetosis and dementia, with onset from childhood to the seventh
      decade. Clinically, DRPLA may be undistinguishable from other genetic disorders,
      in particular Huntington's disease or the spinocerebellar ataxias. The genetic
      basis of the inherited form of DRPLA is an expansion to more than 49 repeats of
      an unstable trinucleotide (CAG) in the DRPLA gene on the short arm of chromosome
      12. We determined the frequency of this mutation in patients with the DRPLA
      phenotype. One hundred and seventeen patients with cerebellar ataxia, from 94
      families and 23 isolated cases, as well as 3 patients from families with
      undiagnosed autosomal dominant neurodegenerative disorders were investigated for
      the presence of the expanded sequence. None of the patients carried this
      mutation. This finding suggests that DRPLA is rare in the French population. The
      search for the DRPLA mutation is justified in patients with the DRPLA phenotype,
      however, since genetic counselling is often requested and neither clinical, nor
      neuropathological examinations permit a definite diagnosis of the underlying
      disease.

PMID- 8745630
TI  - [Potential value of hyperbaric oxygenation in the treatment of post-radiation
      myelopathies].
AB  - We describe 9 patients with radiation myelopathy treated by hyperbaric
      oxygenation (HBO). In this retrospective study, six out of nine (66%) could have
      been stabilized or improved by HBO. Physiopathological mechanisms of radiation
      myelopathy remain controversial and incompletely known. We discuss the putative
      mechanisms of the beneficial action of HBO on radiation myelopathy. Controlled
      studies are required to clarify the interest of HBO in this disease.

PMID- 8745631
TI  - [Acute and reversible myoclonic encephalopathy, extrapyramidal syndrome,
      polyneuropathy caused by chronic disulfiram poisoning].
AB  - This 44-year woman was admitted for weight loss and global intellectual slowing.
      She had mild chronic alcoholic neuropathy. She was discontinued alcoholic
      consumption for 6 months and was given disulfiram (1.5 g/day) since then. She
      developed over a 5-day period acute neuropathy, confusion and extrapyramidal
      symptoms with oculo-cephalogyric and dystonic movements and myoclonus.
      Electromyography revealed a severe polyneuropathy. After disulfiram withdrawal,
      confusion and extrapyramidal symptoms disappeared within a few days, but
      sensitivo-motor deficit improved more slowly. Nerve biopsy was suggestive of a
      pure axonal neuropathy.

PMID- 8745632
TI  - [Electrocardiographic anomalies in relation with infarction in the territory of
      the anterior choroid artery].
AB  - Electrocardiographic changes are seen in 5-17% of acute ischemic stroke, but
      there is scarpe clinical evidence to correlate stroke location with cardiac
      abnormalities. A 17-year old man had infarct in the territory of the anterior
      choroidal artery with major but reversible electrocardiographic changes.
      Infarction involved the substantia innominata containing the ventral
      amygdalofugal pathway. Electrocardiographic changes could result from a small
      hemispheric lesion of structures involved in autonomic control. Correlation
      studies of stroke location with electrophysiologic changes should help to
      determine patients at risk for cardiac arrhythmia and prevent sudden death.

PMID- 8745633
TI  - Use of thermal fluctuations to study the length and flexibility of ligand
      receptor bonds.
AB  - We describe an experimental approach yielding new information on the behavior of
      ligand-receptor bonds. Spherical particles of 1.4 microns radius were coated with
      anti-rabbit immunoglobulin monoclonal antibodies and deposited on surfaces
      derivatized with rabbit immunoglobulins. Brownian motion was studied. When
      particles where bound through multiple bonds, the mean square displacement during
      a 1 s interval was 0.0038 micron2 as compared to 0.245 micron2 for unbound
      particles. Under the same conditions, the mean square displacement of particules
      coated with limiting dilutions of binding sites and bound by single molecular
      bonds was 0.0774 micron2. Results are compatible with the concept that the latter
      particles behaved as spheres transiently bound to the substratum by links of 2.7
      nm length, allowing brownian oscillations with an angular amplitude of 0.062
      radian.

PMID- 8745634
TI  - Secondary structure conservation of the U3 small nucleolar RNA introns in
      Saccharomyces.
AB  - Using a strategy based on PCR amplification of DNA and sequence analysis, we
      showed that the presence of introns with the characteristic features of introns
      spliced in a spliceosome, in the U3A and U3B snoRNA genes that code for the U3
      small nucleolar RNA, is not a property restricted to Saccharomyces cerevisiae. It
      is probably an ancient property of yeasts from the genus Saccharomyces. We
      detected the U3A and U3B snoRNA genes in Saccharomyces bayanus and in a lager
      brewing yeast strain. The U3A and U3B intronic sequences are highly conserved.
      Two additional "U3B-like" snoRNA genes were detected in the lager brewing yeast.
      Their intronic sequences show several differences, when compared to the U3B
      intronic sequence. However, despite the numerous mutations, the intron secondary
      structure is conserved, especially, the central structure. This strongly suggests
      an important role of this central stem/loop structure for spliceosome assembly
      and efficient splicing.

PMID- 8745635
TI  - Gene transfer from bacteria to mammalian cells.
AB  - Transfer of genetic information between phylogenetically remote bacterial genera
      [1], from bacteria to yeast [2] and from bacteria to plants [3] by plasmid
      conjugation has been described. However, direct DNA transfer from prokaryotes to
      mammalian cells has not yet been demonstrated. Certain bacterial species have
      evolved the ability to enter mammalian cells by inducing their own
      internalization [4]. We show that invasive strains of Shigella flexneri and
      Escherichia coli, that undergo lysis upon entry into mammalian cells because of
      impaired cell wall synthesis, can act as stable DNA delivery systems to their
      host. This direct gene transfer is efficient, of broad host cell range and the
      replicative or integrative vectors so delivered are stably inherited and
      expressed by the cell progeny. DNA delivery by abortive invasion of eukaryotic
      cells by bacteria is of potential interest for stimulation of mucosal immunity
      and for in vivo or ex vivo gene therapy of human diseases.

PMID- 8745636
TI  - How do sporozoites of rabbit Eimeria species reach their target cells?
AB  - In all the studies performed on the invasion of the rabbit by sporozoites of 4
      Eimeria species it was shown that the sporozoites first penetrate the duodenal
      epithelium; and then very quickly appear within the IELs of the duodenal
      epithelium. A few hours later they are found in IELs of their specific site of
      multiplication. The relationship between an "extraintestinal" route for
      sporozoites and the IELs homing phenomenon is therefore an exciting hypothesis.

PMID- 8745637
TI  - HIV genome transcription induced by polyoma virus middle T antigen through both
      enhancer- and promoter-dependent LTR activation.
AB  - In order to understand the regulation of HIV genome transcription induced by cell
      stimulation through transmembrane receptors, we have transfected cells with
      polyoma middle T antigen (PyMT) expression vectors, thus mimicking activated
      receptor-dependent cell stimulation. PyMT-expressing Cos7 cells provided an
      environment where transcription of an HIV provirus was activated. PyMT expression
      induced the activity of both enhancer- and promoter-dependent HIV-LTR luciferase
      vectors. Induction of the HIV promoter domain depended on Sp1-binding sites and
      could be blocked by Wortmannin, an inhibitor of phosphatidylinositol 3-kinase
      (PI3K). This indicates that PyMT-induced HIV transcription and replication are
      controlled by both the enhancer and promoter domains of the HIV-LTR. The latter,
      but not the former, was induced in a PI3K-dependent way. Thus at least 2
      different transduction pathways appear to collaborate for induction of full HIV
      genome transcription in activated cells.

PMID- 8745638
TI  - Surface expression of GD3 disialogangliosides in human melanoma cells is
      correlated to both metastatic potential in vivo and radiosensitivity in vitro.
AB  - With an experimental model of spontaneous lung metastases of melanoma developed
      in this laboratory, 7 sublines (variants and clones) with different metastatic
      potential and ganglioside expression were established from a single human
      melanoma cell line M4Be. Clones and variants derived from M4Be have been
      characterized at their surface by their gangliosides expression that were
      determined by flow cytometry with monoclonal antibodies. Gangliosides are
      membrane glycolipids containing sialic acid. Using an in vitro clonogenic assay
      and provided that cells were cultured for no more than 5 passages, variations in
      the cellular radiosensitivity of M4Be and of the 7 sublines were detected. This
      study shows that the lower the expression of GD3 disialoganglioside at the cell
      surface, both the higher their radiosensitivity in vitro and their metastatic
      potential in vivo. These results suggest that highly metastatic human melanoma
      cells are radiosensitive and deficient in surface gangliosides. Strengthening of
      this hypothesis arise from experiments showing that the incubation of
      radiosensitive cells with exogenous ganglioside significantly increases their
      radioresistance in vitro and reduces their metastatic potential in vivo.

PMID- 8745639
TI  - Drug-resistant epimastigotes of Trypanosoma cruzi and persistence of this
      phenotype after differentiation into amastigotes.
AB  - In vitro benznidazole resistance was induced in cloned T. cruzi epimastigotes
      using a continuous drug pressure protocol. Stocks were selected according to
      their previous genetic characterization by multilocus enzyme electrophoresis. All
      the resistant clones were able to grow in long term cultivation in the presence
      of at least 50 microM benznidazole, which is the drug plasma level during
      chemotherapy in man. The highest level of resistance achieved was 220 microM.
      After differentiation of the epimastigote into the amastigote forms, the drug
      resistance level was not affected. In both, the resistant epimastigotes and the
      resistant amastigotes, growth curves exhibited a lower growth rate than the
      sensitive counterparts without affecting the viability of the parasites. These
      data could be significant in basic research, to study the drug-resistance
      phenotype on relevant chemoresistant clones of T. cruzi, and to follow this
      phenotype after in vivo cycles.

PMID- 8745640
TI  - Readjusting the localization of merosin (laminin alpha 2-chain) deficient
      congenital muscular dystrophy locus on chromosome 6q2.
AB  - The laminin alpha 2-chain gene mutations (LAMA2) are responsible for about 50% of
      the cases of classical congenital muscular dystrophy. These patients form a
      clinically homogenous group presenting merosin (laminin alpha 2-chain) deficiency
      in muscle biopsies. The LAMA2 gene has been previously localized on 6q22-23 and
      the disease locus mapped in a 16 cM interval in 6q2 by homozygosity mapping. In
      the present report we establish, by haplotyping additional microsatellites
      markers in 18 consanguineous families, that LAMA2 gene is more centromeric than
      previously thought: between the flanking markers, D6S407 and D6S1705, distant of
      3 cM. In this interval the microsatellite D6S1620 is homozygous for all the
      patients. The localization of LAMA2 gene was confirmed by radiation hybrid
      mapping. The 3 new highly informative markers can be very useful for prenatal
      diagnosis.

PMID- 8745641
TI  - [What are the complications likely to lead to medicolegal problems? How to manage
      them?].

PMID- 8745642
TI  - [Conduction anesthesia and acquired disorders of hemostasis: under what
      conditions is the association possible?].

PMID- 8745643
TI  - [Arguments for conduction anesthesia in children].
AB  - Regional anaesthesia is more and more popular in pediatrics. Many arguments plead
      for its use. The efficient diffusion of local anaesthetics through the nerve
      roots sheet and the epidural space improves success in children. The lack of
      deleterious haemodynamic effect of sympathetic block following spinal and
      epidural blocks is a factor for their use. So is the quality of intra- and
      postoperative analgesia. In addition, the few number of complications is also an
      advantage of regional blocks in children.

PMID- 8745644
TI  - [Arguments against conduction anesthesia in children].
AB  - Regional anaesthesia has been increasingly popular in paediatric patients of all
      ages, especially because some techniques afford excellent per and post-operative
      pain relief. However, side effects may occur. Particularly, systemic toxicity
      from bupivacaine administration is associated with intravascular injection or
      overdosage. Then, we focused anaesthesiologist's attention on some inconvenients
      related with these practices. Regional blockade is most of the time performed in
      conjunction with general anaesthesia. Consequently, these procedures need
      additional time, material and nurses. There are relatively few absolute
      indications for regional anaesthesia in children. The decision for using these
      techniques is influenced by several factors as incidence of complications, local
      technical expertise. Alternative methods to provide per and post-operative
      analgesia being available, advantages and side effects of loco-regional
      anaesthesia have to be opposited. Management of the best method of block, doses
      and local anaesthetics or adjuvants according age, requires likely specific
      teaching in training team. An effort to provide appropriate guidelines and
      training to ward nurses is necessary to improve security when regional blockade
      is used for postoperative analgesia. In every cases, physician's experience is
      the best argument of choice.

PMID- 8745645
TI  - [Conduction anesthesia in patients with heart diseases].
AB  - The effect of epidural/spinal anaesthesia on cardiovascular function results from
      blockade of the sympathetic nervous system and secondly from plasma absorption of
      local anaesthetic agents. Patients suffering from preexisting heart diseases may
      have different responses to epidural or spinal anaesthesia. In patients with
      myocardial ischemia, the decrease in myocardial work and the reduction in heart
      rate induced by cervical or thoracic epidural anaesthesia improve the myocardial
      oxygen balance. Changes in the inotropic state induced by thoracic epidural
      anaesthesia may worsen the haemodynamic condition of patients with heart failure.
      When the spread of the epidural blockade is limited to the lower segments (<
      T12), changes are limited. In high risk patients, the haemodynamic advantages of
      a combined technique (general plus epidural anaesthesia) and the protective
      effect on the occurrence of myocardial ischemia and related complications are a
      matter of interest. Part of the beneficial effect of epidural anaesthesia could
      be related to postoperative analgesia and its effects on stress response and
      haemostasis.

PMID- 8745646
TI  - [Conduction anesthesia and the newborn infant].
AB  - The placental transfer of local anaesthetics (LA) depends on maternal, placental
      and fetal factors. The assessment of effects of LA and epidural anaesthesia (EA)
      on the fetus is based on the monitoring of fetal heart rate (FHR) and the
      measurement of the fetal pH. Apgar score and neurobehavioral tests allow an
      evaluation of the neonatal effects of the drugs used. Direct effects of LA: a
      diminution of variability of FHR was observed shortly after the beginning of an
      EA using lidocaine but there was no modification of FHR after EA using
      bupivacaine or lidocaine with epinephrine. Fetal neurological toxicity is rare
      and there are very few alterations of neurobehavioral scores after EA. Indirect
      effects on uteroplacental blood flow (UBF): in high concentration, LA can induce
      vasoconstriction of uterine arteries but maternal arterial hypotension that
      impedes directly uteroplacental blood flow is the main effect. Prevention of
      aortocaval compression is essential because it allows better Apgar scores and
      arterial pH at birth. Use of colloids has not a better preventive efficacy than
      an equal volume of cristalloids while dextrans are formally contra-indicated
      because of serious fetal accidents. Large iv infusion of dextrose solutions are
      responsible for maternal and fetal hyperglycemia and hyperinsulinemia leading to
      neonatal hypoglycemia. The utilization of IM prophylactic ephedrine is not useful
      while the therapeutic administration of ephedrine to treat maternal arterial
      hypotension is efficient. Phenylephrine used in case of maternal arterial
      hypotension seems as efficient as is ephedrine. Epidural narcotics: the use of
      morphine by epidural route can induce neonatal respiratory depression and low
      neurobehavioral scores. The epidural administration of fentanyl does not alter
      the variability of the FHR and does not modify neither Apgar or neurobehavioral
      scores, nor respiratory adaptation of the newborn. Use of epidural alfentanil or
      sufentanil does not lead to low neurobehavioral scores unless very high doses are
      used. For elective caesarean section, newborns present a lower Apgar score at 1
      min and necessitate respiratory assistance more frequently after general
      anaesthesia (GA) than after EA. Neurobehavioral scores are better after EA than
      after GA. For emergency caesarean section, the percentage of newborns with an
      Apgar score < 4 or necessitating a respiratory assistance is more important after
      GA than after EA. However, the perinatal mortality is not more important after GA
      than after EA.

PMID- 8745647
TI  - [Epidural anesthesia--at any time].

PMID- 8745648
TI  - [Analgesia after surgery of the spine in adults and adolescents].
AB  - Postoperative pain after spinal surgeries is highly dependent on the number of
      vertebrae included in the operation and on its invasiveness, opposing two
      extremes, discectomies and cyphoscoliosis corrections. Opiates by intravenous
      route remain the reference, either continuously given in predetermined doses, or
      better using a patient-controlled device. Nonsteroidal and steroidal anti
      inflammatory drugs are widely popular for medical approach of sciatalgia and it
      is quite logical to use them for reducing, even to suppress, opiates after spinal
      surgeries. Supported by many studies, spinal administration of analgesics
      (opiates, alpha 2-agonists, corticosteroids) may be of interest in pain treatment
      of spinal surgeries. In order to prolong locoregional analgesia, a catheter may
      be inserted into epidural space by caudal route or surgically, before skin
      closure. Morphine is the most popular agent in this indication. Also, epidural
      clonidine results in excellent pain relief, but is associated with hypotension
      and marked sedation. In discectomy, injection of dexamethasone into the operative
      field has been proposed. Whatever the technique used, early diagnosis of
      neurological complications of spinal surgery should be not ruled out by
      postoperative analgesia.

PMID- 8745649
TI  - [Reflex sympathetic algodystrophies. Preventive and therapeutic aspects].
AB  - Deafferentation syndromes have in common the existence of a physical injury
      and/or of a functional impairment of a nerve, either somatosensory afferent
      (Phantom Limb Pain) and/or sympathetic efferent (Reflex Sympathetic Dystrophy).
      These progressively debilitating syndromes are the witness of the absence of self
      limitation of neuronal sensitization, which is normally the evolution of any
      painful stimulation of spinal cord neurons. To some extent deafferentation
      syndromes could be defined as a maladaptive neuronal plasticity. The lack of
      complete understanding of underlying pathophysiological mechanisms gives account
      of the wide variety of proposed treatments and of their unpredictable and
      variable efficacy. This fact is also due in part to the lack of controlled
      studies of most of the therapeutic propositions, whose purported efficacy is
      usually based on anecdotal reports. Finally, the role of prevention must be
      strongly emphasized, focusing, if those syndromes are likely to occur following
      surgery, on the importance of pre- and postoperative efficient analgesia, and
      also, possibly, on the preemptive role of regional anaesthetic techniques.

PMID- 8745650
TI  - [Pain and tourniquet in orthopedic surgery].
AB  - The use of a pneumatic tourniquet to provide a bloodless field in orthopedic
      surgery is often complicated by tourniquet pain. The mechanism of this pain
      remains incompletely understood, but it is probably multifactorial. Nerve
      compression is a common etiologic feature. The use of local anaesthetics may be
      considered the best choice for avoiding tourniquet pain. Superficial (skin)
      compression and deep components compression like blood vessels and muscles can
      both induce tourniquet pain. Central nervous system can also interfere. Release
      of tourniquet can increase the pain by post-ischaemic oedema due to ischaemia and
      reperfusion injury.

PMID- 8745651
TI  - [Analgesia after surgery of the shoulder].
AB  - Postoperative pain after shoulder surgery is known to be intense and requires
      usually opioid administration. The recent use of regional anaesthesia for this
      type of surgery has contributed to the relief of acute postoperative pain
      occurring in the recovery room since the analgesic effects of block persist for
      several hours after surgery depending upon the selected drug. Moreover, the
      development of less invasive surgery (arthroscopy) and experience with regional
      blocks have permitted to perform minor shoulder surgery on an outpatient basis.
      For minor surgery, regional anaesthesia associated to a light sedation is
      sufficient. However, for more invasive surgery, regional anaesthesia should be
      associated to a light general anaesthesia as well as the insertion of a
      supraclavicular catheter for postoperative analgesia. A diaphragmatic paresis
      secondary to a blockade of the phrenic nerve is constant radiologically after
      interscalenic block but remains symptomless. However, in case of severe
      preoperative chronic respiratory insufficiency, decompensation may occur rapidly
      after performance of the interscalenic block.

PMID- 8745652
TI  - [Patient-controlled analgesia in cancer pain: practical aspects].
AB  - Allowing a suffering patient with cancer to control his pain is a challenge that
      numerous medical teams intend to take up. Although the best treatment is the
      etiologic one, in many situations the symptomatic and adjuvant therapies are both
      indispensable. Among them, the patient controlled analgesia (PCA) is a concept
      referring to the management of the pain, but also to the administration of some
      analgesic drugs. Even with genuine advantages the limits of the PCA do exist and
      need to be well known. PCA is not limited to palliative treatment; it can be used
      in many circonstances during each evolutionary step of the cancer, temporarily or
      for longer periods, at the hospital and at home as well. All patients disposing
      of such an equiment could determine their own best level of analgesia, at the
      good time, depending upon the temporal variability of the pain and its
      previsibility or not. The availability and the pedagogic concern of the members
      of the team, the link between the patient and his family, the involvement of both
      the regular general practioner and the "algologic" team are essential to maintain
      the best effects of this method.

PMID- 8745653
TI  - [Blocking of the brachial plexus: which technique(s) should be chosen?].
AB  - Brachial plexus blocks for upper extremity surgery: what are the preferred
      techniques? Brachial plexus anaesthesia for all types of upper extremity surgical
      procedures cannot be adequately achieved with a single technique. At least, two
      approaches are required: above the clavicle, Winnie's interscalene brachial
      plexus block, using a neurostimulator, has become the standard technique for
      shoulder surgery. Below the clavicle, midhumerus approach is the most successful
      approach for elbow, fore arm and hand surgery, especially for outpatient surgery.
      The best approach for catheter insertion along brachial plexus nerves/trunks
      remain controversial. The supraclavicular approach using surface landmarks might
      be the best approach due to its efficacy in achieving complete anaesthesia of the
      upper extremity and the rarity of secondary displacement of the catheter.
      Whatever the selected approach(es) to brachial plexus nerves, nerve location it
      best achieved by neurostimulation and often multiple neurostimulation. Insulated
      needles are being increasingly used due to accuracy but, currently, there is no
      general agreement concerning the type of needle bevel to be preferred in regard
      to both safety and accuracy.

PMID- 8745654
TI  - [Nerve block analgesia after surgery of the knee].
AB  - Lumbar plexus block via the inguinal approach is indicated for analgesia
      following knee surgery. The technique consists in an injection of the anaesthetic
      solution through a catheter placed into the space limited by the fascia of the
      iliopsoas muscle. In this area are the different nervous roots which constitute
      the plexus. A good technique and a good knowledge of the anatomy of this region
      are necessary for a successful block and for the safety of the patient.

PMID- 8745655
TI  - [Conduction anesthesia and analgesia in emergency cases. From pain to its
      treatment].
AB  - The study of pathophysiological and symptomatological characteristics of pain in
      emergency situations, and of its harmful consequences, shows that, in spite of a
      difficult context, analgesia is an essential part of the care to patients during
      the prehospital stage. Its prescription implies a good knowledge of analgesia
      techniques, including precise rules such as titration. The choice of analgesia
      must be the outcome of a rigorous step giving priority to the vital functions and
      associating several techniques. Regional anaesthesia is not very often used in
      prehospital emergency but rather in emergency units and in the surgical ward.
      Analgesia must be adapted, mainly to specific situations in emergency: children,
      old people, burned people with pain.

PMID- 8745656
TI  - [Conduction anesthesia on an outpatient basis].
AB  - Regional anaesthesia in the setting of pre-hospital trauma care implies adverse
      conditions. Therefore some practical advices may be useful; avoid spinal or
      epidural anaesthesia, prefer safer lidocaine. Aspiration test, test dose and slow
      injection are mandatory; so is a large experience in regional anaesthesia. Main
      usable blocks are: brachial plexus block (axillary or interscalenic approach),
      radial, medial and ulnar nerve blocks, intercostal and interpleural nerve blocks,
      sciatic and femoral nerve blocks, superior laryngeal nerve block. Using a nerve
      stimulator is strongly advised in most cases.

PMID- 8745657
TI  - [Should Doppler echography in the diagnosis of the extra-cardiac sites of
      atherosclerosis be routine in patients with coronary disease? Apropos of 248
      cases].
AB  - Doppler ultrasound investigation of cervical and aorto-iliac arteries, performed
      in 248 patients investigated by coronary angiography (including 80% with coronary
      heart disease: 23% single-vessel, 23% two-vessel and 34% three-vessel disease)
      confirmed the frequency of dissemination of the atheromatous process (in the
      cervical vessels: non-stenotic atheroma: 45%, significant single- or multi-vessel
      stenoses: 16%, in the aorto-iliac vessels: non-stenotic atheroma: 32.8%,
      significant stenoses: 17.2%), which has been known for a long time. The
      unreliability of clinical examination, the reliability, safety and low cost of
      ultrasound, the discovery of a considerable number of critical, potentially
      dangerous arterial lesions, some of which may require a surgical procedure or
      angioplasty (3.4%), the value of assessing, either before coronary angiography or
      before cardiac surgery, certain specific arterial territories such as the aortic
      bifurcation and subclavian vessels, justify systematic use of this examination in
      coronary patients, particularly before coronary angiography and always before
      coronary surgery.

PMID- 8745658
TI  - [Effort-induced atrioventricular block. Apropos of 62 cases].
AB  - Based on a retrospective study, we report the clinical and electrophysiological
      characteristics of 62 cases of effort-induced atrio-ventricular block (AVB). The
      diagnosis of effort-induced AVB was established by stress test and/or Holter ECG.
      This series consisted of 18 women and 44 men with a mean age of 64 +/- 13 years.
      AVB presented in the form of poor adaptation to effort in 41 patients (66%),
      fainting and/or presyncope suggestive of Stokes-Adams attacks in 20 patients
      (32%), associated with poor adaptation to effort, except in 5 patients. 48
      patients (77%) did not have any underlying heart disease. The ECG was normal in
      25 patients (40%) or abnormal, demonstrating a 1st degree AVB and/or an
      intraventricular conduction disorder. On electrophysiological investigation, the
      AVB was type II (Mobitz II) in 48 patients (77%), generally 2/1. The block was
      infranodal, either in or below the His bundle, in 56 patients (90%). When it was
      situated above the His bundle, it was organic and degenerative, situated at the
      AV node, at the node-His junction, or even proximally in the His bundle. Effort
      induced AVB implies DDD atrioventricular stimulation. The presence of this
      anomaly should be investigated in patients with poor adaptation to effort, but
      also when the clinical picture is dominated by Stokes-Adam attacks.

PMID- 8745659
TI  - [Value of early stress test during treatment after myocardial infarction with Q
      wave in patients under 55 years of age].
AB  - We studied one hundred consecutive patients, under the age of 55 years (mean age:
      45.6 years), with myocardial infarction and a Q wave, in order to assess the
      prognostic value of an early stress test. Thirty five patients were excluded: 2
      deaths, 21 revascularizations during the acute phase, 4 tests were performed
      without treatment, 6 tests were unable to be performed and 2 patients left
      hospital against medical advice. Sixty five patients [males, n = 60 (92.2%),
      anterior infarction, n = 25 (38.5%), thrombolysed n = 35 (53.8%), intact left
      ventricular ejection fraction (mean: 54.7%)] systematically underwent a stress
      test limited by symptoms, in hospital, on the tenth day of infarction, using an
      ergometric bicycle and under medical treatment (including beta blockers n = 47
      (72.2%)] and cardiac catheterization. The test was considered positive when it
      was accompanied by angina and/or ST depression (n = 19), negative in the absence
      of these criteria for a level of 120 watts (n = 23), inadequate when the duration
      was less than 9 minutes and when the heart rate was less than or equal to 70% of
      the theoretical maximal heart rate (n = 11), doubtful when there was accentuation
      of ST elevation in the infarcted territory with mirror ST depression (n = 12).
      Only 30.7% of patients had multi-vessel coronary lesions (two- and three-vessel
      disease). The mortality was 4.6% with a mean follow-up of 27.4 months (range: 3
      38). The sensitivity of the test for detection of multi-vessel disease was 62.5%,
      the specificity was 65.3%, the positive predictive value was 52.6%, and the
      negative predictive value was 73.9%. The sensitivity of this test, with beta
      blocker treatment, to predict coronary lesions or cardiac events, fell to 33.3%
      and 37.5%, respectively. The stress test during the post-infarction period, with
      beta-blocker treatment, appears to be less sensitive for the identification of
      multivessel disease and cardiac events: this treatment should therefore be
      suspended before performing this test when allowed by the patient's clinical
      state.

PMID- 8745660
TI  - [Correlation between transthoracic and transesophageal echocardiography and
      surgery in mitral stenosis].
AB  - This prospective study was designed to analyse transthoracic and transesophageal
      echocardiographic findings in the morphological study of the mitral valve and to
      compare them with surgical findings. This study was based on a series of 60
      consecutive patients (38 men and 22 women with a mean age of 36.3 +/- 4.2 years)
      undergoing open heart surgery for pure or very predominant symptomatic mitral
      stenosis between November 1993 and December 1994. All patients were investigated
      by transthoracic and transesophageal echocardiography an average of 3 days before
      the surgical operation. Qualitative analysis of the mitral valve was rigorously
      performed according to a 4-point severity score taking into account mobility,
      thickness and degree of valve calcification as well as the condition of the
      subvalvular apparatus. The global echocardiographic score corresponded to the sum
      of the scores for these 4 elements. Transesophageal echocardiographic data and
      surgical findings were identical: global score: 9.3 vs 9.5, mobility: 2.8 vs 2.9,
      thickness: 2.6 vs 2.5, calcifications: 1.7 vs 1.8, condition of the subvalvular
      apparatus: 2.2 vs 2.3. The degree of valve damage was overestimated by
      transthoracic echocardiography compared to surgical data: global score: 10.4 vs
      9.5 (p < 0.05), mobility: 3.1 vs 2.9 (p < 0.05), thickness: 2.8 vs 2.5 (p <
      0.01), calcifications: 2.1 vs 1.8 (p < 0.01), but the difference was not
      significant for the condition of the subvalvular apparatus: 2.4 vs 2.3. In
      conclusion, surgical findings in pure or very predominant mitral stenosis are
      more closely correlated with transesophageal echocardiographic data than with
      transthoracic echocardiography, which tends to overestimate the severity of
      anatomical lesions, particularly valvular calcification.

PMID- 8745661
TI  - [Obstructive sleep apnea syndrome and cardiovascular diseases].
AB  - Obstructive sleep apnoea syndrome is due to pharyngeal obstruction of inspiratory
      airflow with preservation of thoraco-abdominal respiratory movements. This
      disease has been described for about thirty years, but is now the subject of
      growing interest. According to the increasingly abundant literature on this
      subject, OSAS is associated with essentially cardiovascular morbidity and
      mortality (systemic hypertension, pulmonary hypertension, heart failure, coronary
      heart disease, arrhythmias, cerebral vascular accidents and sudden death). The
      pathophysiology of its underlying mechanisms and its complications is complex and
      multifactorial. The diagnosis of this syndrome should be suspected on clinical
      interview (snoring, excessive daytime drowsiness, and apnoea during sleep) and is
      confirmed by polysomnography. Nasal continuous positive pressure with elimination
      of aggravating factors is the reference treatment in 1994. The diagnosis and
      management of this syndrome requires a multidisciplinary approach with
      collaboration between general practitioners, neurologists, maxillofacial/ENT
      surgeons, cardiologists and respiratory physicians.

PMID- 8745662
TI  - [Evaluation of trandolapril alone or in combination with a calcium channel
      blocker in hypertensive patients over 60 years of age].
AB  - The efficacy and safety of trandolapril alone and in combination with a calcium
      channel blocker were evaluated in 13,147 hypertensive patients over 60 years old.
      Two patient groups were constituted. After a 2-week wash-out period, the patients
      in group I received monotherapy with trandolapril 2 mg/day for 4 weeks.
      Trandolapril was continued for another 4 weeks in responding patient, otherwise
      the dosage of trandolapril was doubled or another antihypertensive was added.
      Group 2, composed of patients previously treated with a calcium channel blocker
      with insufficient efficacy, was treated according to the same treatment regimen,
      but the calcium channel blocker was maintained throughout the study. 13,147
      patients (group 1: 11,329 patients, group 2: 1,818 patients) with a mean age of
      68 +/- 7 years were followed. After 4 weeks of treatment, the blood pressure
      measured by mercury sphygmomanometer decreased from 176 + 11/99 +/- 8 mmHg to 164
      +/- 12/87 +/- 7 mmHg (p < 0.0001). This blood pressure fall was similar in group
      1 (-22 +/- 12/-12 +/- 8 mmHg) and in group 2 (-21 +/- 11/-12 +/- 8 mmHg). In the
      pure systolic HT subgroup treated by trandolapril monotherapy, the
      antihypertensive effect predominantly affected the SBP (-23 +/- 12/- 4 +/- 6
      mmHg). The antihypertensive effect was correlated with the initial blood
      pressure. In group 1, in the case of insufficient response to trandolapril
      monotherapy, the addition of a calcium channel blocker was the strategy which
      achieved the most marked antihypertensive effect (ANOVA, p < 0.0001). This
      bitherapy was more effective than the trandolapril+diuretic combination (-18 +/-
      11/- 11 +/- 8 mmHg and -15 +/- 10/- 9 +/- 7 mmHg, respectively (p < 0.001). A
      total of 1,270 adverse events were reported by 996 patients (7.6%), leading to
      discontinuation of treatment in 372 patients (2.8%). The most frequent adverse
      effects were cough (2.8%), headache (0.8%), vertigo (0.8%) and nausea (0.5%).
      Only one minor equivalent of angioneurotic oedema was reported. In conclusion,
      trandolapril is effective and well tolerated in elderly hypertensive patients. In
      the case of pure systolic HTA, its action is essentially exerted on SBP. The
      combination of trandolapril+calcium channel blocker appears to be the most
      effective strategy in the case of incomplete blood pressure control by
      trandolapril alone.

PMID- 8745663
TI  - [Comparative effects of cibenzoline and hydroquinidine in the prevention of
      auricular fibrillation. A randomized double-blind study].
AB  - The objective of this study was to compare the efficacy and safety of cibenzoline
      (130 mg twice a day) and sustained-release hydroquinidine (300 mg twice a day) in
      the prevention of recurrent atrial fibrillation (AF). This randomized double
      blind study was conducted in 87 patients, with a mean age of 62 years, presenting
      with a history of AF for 72 hours to a maximum of 3 years. After restoration of
      sinus rhythm, in order for the subjects to be included in the study,
      echocardiography had to reveal a left ventricular shortening fraction of more
      than 20%. Patients were followed for one year by clinical examination, ECG and 24
      hour Holter monitoring performed 7 days after inclusion, then after 3, 6, 9 and
      12 months. The two groups, treated with either cibenzoline (n = 40) or
      hydroquinidine (n = 44), were comparable. The AF recurrence rates with
      cibenzoline or hydroquinidine were 34.9% had 36.4% at 6 months, and 41.9% and
      43.2% at 12 months, respectively (NS). Most recurrences occurred during the first
      month. Adverse effects were reported in 10 patients (23.3%) with cibenzoline and
      12 patients (27.3%) with hydroquinidine. They led to discontinuation of treatment
      in 6 patients (14%) treated with cibenzoline and 5 patients (11.4%) treated with
      hydroquinidine. Serious adverse events included one death from hypoglycaemic coma
      and one case of persistent ventricular tachycardia with hydroquinidine. In
      conclusion, oral cibenzoline demonstrated the same antiarrhythmic activity as
      hydroquinidine in the long-term prevention of recurrent atrial fibrillation, with
      a similar degree of safety. This drug can therefore constitute an alternative to
      conventional antiarrhythmics in this context.

PMID- 8745664
TI  - Homoharringtonine: an effective new natural product in cancer chemotherapy.
AB  - Homoharringtonine (HHT) is a cytotoxic alkaloid isolated from the evergreen tree
      cephalotaxus harringtonia native to the southern provinces of China. The
      principal mechanism of action of HHT is the inhibition of protein synthesis in a
      dose- and time-dependent manner by acting on the ribosomes of cancer cells. It
      blocks the progression of cells from G1 phase into S phase and from G2 phase into
      M phase. It is synergestic or additive in vitro with AraC, amsacrine, actinomycin
      D and dexamethasone. Clinical studies have indicated that HHT is effective in
      treating acute myeloid leukemia (AML), chronic myeloid leukemia (CML) and
      myelodysplastic syndrome (MDS), but not acute lymphoblastic leukemia (ALL) and
      solid tumors. The dose limiting toxicities are hypotention and myelosuppression.
      Homoharringtonine has relatively mild extramedullary toxicities and no
      anthracycline-like cardiac toxicity, which make it a suitable candidate for the
      treatment of aged patients. Pharmacological studies indicate that HHT belongs to
      the category of multidrug resistance (MDR)-related drugs. The cells resistant to
      HHT are cross-resistant to anthracycline, vinca alkaloids, mitoxantrone, but not
      cis-platine and AraC. Multiple mechanisms, including the sequential emergence of
      overexpression of multidrug resistance-associated protein (MRP) and MDR1 genes,
      are involved in the cross-resistance of tumor cells to HHT.

PMID- 8745665
TI  - [Localized small-cell lung cancers: prospects of concomitant radiochemotherapy].
AB  - Concurrent chemoradiotherapy in the treatment of small-cell lung cancer: current
      results and future prospects. The prognosis of small cell carcinoma of the lung
      is reportedly poor, even in limited disease. However, new modalities of combined
      chemotherapy and radiotherapy may actually result in improved survival in these
      patients. First-line chemotherapy regimens with cisplatin and etoposide are
      effective and allow early and concurrent administration of thoracic radiotherapy,
      without overwhelming toxicity. Radiosensitizing properties of cisplatin and
      etoposide have been demonstrated, and concurrent delivery of radiotherapy results
      in a high complete response rate on the primary tumor, and improved long-term
      local control, which is a prerequisite for cure. In addition, a reduction of the
      irradiated volume, restricted to the macroscopic tumor, appears feasible without
      compromising local control and results in a reduced long-term complication rate
      of the combined treatment. Acute toxicities of these concurrent regimens are
      mainly hematological and esophageal, but are reversible and without late effect
      in the majority of the patients. The potential benefit of a twice-daily over
      standard once-daily irradiation has not been conclusively demonstrated in recent
      trials. However, these trials have demonstrated excellent outcome after short
      duration chemotherapy (four courses) with early concurrent radiotherapy (45 Gy),
      resulting in a 40% survival at 2 years, which appears substantially higher than
      that obtained with the sequential or alternating regimens. The benefit of
      prophylactic cranial irradiation has also been confirmed in a large trial in
      terms of reduction of brain relapses, but with only marginal benefit upon
      survival. Further improvement of the prognosis of these patients may result form
      an early intensification of chemotherapy with the support of hematopoietic growth
      factors and from a dose escalation of radiotherapy with the support of three
      dimensional computerized dosimetry.

PMID- 8745666
TI  - [Chemotherapy of metastatic endometrial carcinoma. Review of the literature].
AB  - Endometrial carcinoma is one of the most common gynaecological cancers in Western
      countries. About 75% of the patients present limited disease, confined to the
      uterus that can be cured by surgery. However, one third of the patients will need
      systemic treatment because of metastatic or relapsing disease. Hormonotherapy
      response rates are less than 20%. In monochemotherapy, the higher response rates
      are constantly observed with doxorubicin or cisplatinum (25-35%). Most commonly
      used combination are CAP (cyclophosphamide, doxorubicin, cisplatinum) or AP
      (doxorubicin, cisplatinum), giving 35 to 60% of objective responses. Recent
      results of large randomized trials have demonstrated marginal, if any, effect of
      cyclophosphamide and superiority of doxorubicin-cisplatinum combination compared
      to doxorubicin alone for response and survival. Chemotherapy as hormonotherapy
      remains palliative. Median response duration is 4 to 6 months and median overall
      survival duration is 7 to 10 months. Currently, hormonotherapy-chemotherapy
      combination have not been proved to be more effective than chemotherapy alone.

PMID- 8745667
TI  - [Prognostic value of pre-therapeutic levels of carcino-embryonic antigen in
      primary bronchial carcinoma].
AB  - To evaluate the pronostic value of an elevated seric carcinoembryonic antigen
      (CEA > 10 ng/ml) at diagnosis, in patients with lung cancer, a pair study was
      done: couples of patients with same staging and histologic type were established,
      one patient with high CEA level compared to one patient with normal CEA level (<
      5.5 ng/ml). Other markers were measured: neuron specific enolase (NSE), squamous
      cell carcinoma (SCC) or Cyfra 21-1. Survival was the end point of comparison. For
      89 couples created, patients with low CEA level had a better survival rate at one
      year ( p = 0.02), this prognosis advantage was confirmed by a comparison of
      survival curves with Mantel-Cox and Breslow test (p = 0.01), but not by the signs
      test. These differences were also observed for the 71 couples of squamous cell
      carcinomas and adenocarcinomas, and the apparied signs test was still not
      significant. The poor prognosis persisted for patients with high CEA level, when
      one another marker's level (NSE or SCC or Cyfra 21-1) was increased, in
      comparison with patients with any marker increased. On 29 couples of all
      histological subtypes or on the 25 couples of non small cell lung cancer, the
      signs test and the comparison of survival curves were significant, but not the 1
      year survival rate. This study shows that a CEA level greater than 10 ng/ml at
      diagnosis is a poor pronostic factor in patients with lung carcinoma, independent
      of the stage of disease and of the histologic type.

PMID- 8745668
TI  - [Stability of 5-fluorouracil solutions according to different parameters].
AB  - To follow therapeutic evolutions and to ensure an international homogeneity,
      "Produits Roche" Laboratories recently modified the conditioning of 5
      fluorouracil (5-FU): the Tris buffer was replaced by sodium hydroxide (pH 9.4).
      For these newly-formulated 5-FU solutions, we studied the optimal conditions of
      storage according to concentration (0.2; 1.5 and 10 mg/ml), temperature (4, 21
      and 37 degrees C), light (without, natural, artificial) and duration (7, 15 and
      30 days) for plastic bags, syringes and cassettes. 5-FU was dosaged by High
      Performance Liquid Chromatography (HPLC). No staining was observed, but for the
      samples placed at 4 degrees C, we detected macroscopically the apparition of
      crystals, more or less rapidly according to 5-FU concentration. For plastic bags
      at 0.2 mg/ml of 5-FU in NaCl (0.9%), 48 hours were sufficient for
      crystallisation. For preparations at 10 and 50 mg/ml, the formation of crystals
      occurred in less than 24 hours. However, no microscopic analysis was performed
      and therefore, in shorter delays, the formation of microcrystals can be
      envisaged. After 7 days, only the storage in darkness at 21 degrees C yields good
      results of stability for cassettes and syringes at 50 mg/ml with a degradation of
      the active component that does not exceed 2%. However, in the same optimal
      conditions, a storage superior to 14 days cannot be envisaged since we noted a
      10% diminution of the active component, then this loss intensifies and reaches
      18% after 30 days of storage. For plastic bags at 0.2 and 1.5 mg/ml of 5-FU, we
      did not measure any significant difference between the various storage
      conditions, even during 14 days. At 10 mg/ml concentration, a storage during 7
      days in darkness can be envisaged with no repercussion on the 5-FU stability.
      Independently of concentration, special attention must be paid to the risk of
      crystallisation at 4 degrees C.

PMID- 8745669
TI  - [Salvage therapy of relapsing or refractory malignant lymphoma with non
      myelotoxic combined chemotherapy. Results of combination of cisplatin, bleomycin,
      methyl-GAG and prednisolone (Cis-BMP)].
AB  - Fifty-one patients with primary refractory or relapsed malignant lymphoma (47 non
      Hodgkin's lymphoma and four Hodgkin's disease) were treated with a new
      chemotherapeutic regimen (cisplatinum, methyl GAG, bleomocyin, methyl
      prednisolon). Among these 51 patients, 41 had measurable disease. Three of these
      41 patients achieved complete remissions (7.3%) and 17 showed partial response
      (41.5%). The low hematological toxicity of this chemotherapeutic combination
      allowed us to give the full dose at the planned cycle date in 90% of the cycles.
      No major toxicity were observed (two minor neurological toxicities, one
      ototoxicity associated with oral mucositis toxicity, 6 febrile episodes) during
      164 courses. With a median follow-up of 12 months, 18% of patients were alive
      without disease. We conclude that in this particular population of malignant
      lymphomas, Cis-BMP is an effective therapy with minimal toxicity.

PMID- 8745670
TI  - Granisetron (IV) compared with ondansetron (IV plus oral) in the prevention of
      nausea and vomiting induced by moderately-emetogenic chemotherapy. A cross-over
      study.
AB  - The French Northern Oncology Group carried out a randomised, cross-over study
      comparing two anti-emetic treatment strategies in 150 chemotherapy-naive
      patients, receiving their first two courses of moderately-emetogenic drugs.
      Nausea and vomiting were assessed using a self-administered questionnaire for
      five days. Anti-emetic treatments consisted of granisetron (G) 3 mg intravenously
      (iv) before chemotherapy or ondansetron (O) 8 mg intravenously, followed by 8 mg
      orally every eight hours for the next three days (for a total of 9 tablets). No
      significant difference was detected between treatment regimens in terms of their
      ability to control either acute vomiting (no vomiting - G = 72%; O = 77%) or
      acute nausea (no nausea - G = 54%; O = 47%), nor in terms of the number of total
      responders, (no emesis and no nausea) on day 1 (G = 52%; O = 45%) or on days 1- 5
      ( mean G - 37%; O = 32%). Furthermore, there was also no significant difference
      between patient preference for the two treatments, either with regard to efficacy
      (G = 39%; O = 34%) or tolerability (G = 29%; O = 27%). In conclusion, no
      difference was observed between the two treatments.

PMID- 8745671
TI  - [Concomitant radiochemotherapy with cisplatin (CDDP), 5-fluorouracil (5-FU) and
      mitomycin C (MMC) in locally advanced carcinoma of the oropharynx. Results of a
      phase II trial].
AB  - In order to improve loco-regional control in locally advanced oropharyngeal
      carcinoma, a phase II trial was designed to establish the feasibility of
      concomitant conventional radiotherapy and three cycles of chemotherapy at day 1,
      21 and 42 with cisplatin (CDDP) 20 mg/m2 and 5-fluorouracil (5-FU) 400 mg/m2 day
      1 to day 4, and mitomycin C (MMC) 10 mg/m2 day 1. From March 1990 to September
      1993, 27 patients (mean age: 55) were included in this study. Three patients
      (11%) were T2N0, 19 (70%) T3 (T3N0: n = 9, T3N1: n = 1, T3N2: n = 5, T3N3: n =
      4), and 5 (19%) T4 (T4N0: n = 1, T4N1: n = 1, T4N2: n = 2, T4N3: n = 1). With a
      mean follow-up of 34 months (17-59), ten patients (37%) were alive, free of
      disease; among the 17 other patients, seven died with cancer. Loco-regional
      control rate was 85%. One and 2-year survival rates were respectively 48 and 31%
      for overall and disease-free survival; respective corrected overall survival
      rates were 68 and 61%. Grade 3 or 4 mucositis was 81%; enteral feeding was
      necessary for 63% of the patients; mean loss of weight was 5.7 kg. Grade > 2
      thrombopenia occurred in 11 patients (41%), grade > 2 neutropenia in eight
      patients (29%) , grade > 2 anemia in four patients (15%). Febrile neutropenia or
      aplasia occurred in five patients (19%). Two patients (7%) died during treatment
      of haematological or infectious complications related to the treatment. Another
      patient died 2 months after treatment with grade 4 thrombopenia and septicemia.
      Addition of MMC to 5-FU and CDDP might have been partly responsible of this
      increased toxicity. A high complete response rate has been achieved with this
      concomitant radio-polychemotherapy, but with a severe digestive and
      haematological toxicity, which did not allow to conclude to the feasibility of
      this therapeutic association.

PMID- 8745672
TI  - [Feasibility and tolerance evaluation of 2 routes of preoperative administration
      of interleukin 2].
AB  - Preoperative interleukin 2 (IL2) administration has been performed, in order to
      diminish the post-operative immunodepression in cancer patients. The aim of this
      study was to compare two different ways of preoperative IL2 administration, ie,
      intravenous (iv) and subcutaneous (sc), in terms of feasibility and tolerance.
      Nineteen surgical procedures were performed in 18 patients: a) 10 following the
      administration of 12 IU/m2/24 hours IL2 IV, with a continuous infusion, from day
      5 to day 3 before surgery; b) 9 following the administration of 18 IU IL2, in 2
      SC injections per day, from day 4 to day 2 before surgery. Tolerance was
      evaluated by both clinical and biological parameters, before, during, and after
      surgery. Hyperthermia and capillary leak syndrome were more important in the iv
      versus sc injection group. Insomnia and digestive troubles were more frequent in
      the iv injection group as well. However, we noticed few and equivalent cutaneous
      and respiratory complications in both groups. In conclusion, the tolerance of IL2
      was better after sc versus iv injection. However, the toxicity of iv infusion of
      IL2 was moderate and could be limited by preventive treatments; moreover there
      was no consequence on the scheduled surgical procedure.

PMID- 8745673
TI  - [Thyroid oncology in ORL practice. Apropos of 87 cases].
AB  - The authors report a high thyroid cancer incidence. The thyroidite and the
      patient age explain it. The thyroidectomy is not subordonated by an extemporane
      histologic examination.

PMID- 8745674
TI  - [Methodology of the evaluation of antiemetics].
AB  - A number of clinical trials have only recently been conducted in the evaluation
      of chemotherapy-induced emesis prophylaxis. This is related to the development of
      new antiemetic drugs, the 5-HT3 serotoninergic receptors antagonists which are
      very effective. Methodological principles of drug development have been respected
      for the commercialization of this new class of antiemetics. The essential phase I
      and II studies have allowed to establish the maximal tolerated doses and the
      efficacy-dose relation in order to conduct phase III clinical trials. At this
      time, the reference treatment for emesis was metoclopramide and thus, phase III
      trials have been initially conducted with this comparative treatment. These
      randomized studies have been carried out in parallel group and in double-blind in
      accordance with a methodology adapted to cancer. The inclusion criteria have
      allowed to define an homogeneous population of chemotherapy naive patients and
      clinical trials have been conducted with a stratification related to the emetic
      power of the chemotherapy. The number of patients to include in the studies was
      calculated related to the expected efficacy rates of the comparative drugs. The
      evaluation criteria of nausea and vomiting were standardized and the primary
      clinical end point to assess the efficacy of antiemetic agents was determined by
      a complete control (no emetic episode). Nausea, which is a more subjective
      criterion, was assessed by the patient himself and the results could be included
      in the global analysis. Furthermore, the persistence of the efficacy over
      repeated courses has been assessed by clinical trials carried out on two to six
      cycles.

PMID- 8745675
TI  - [Future trends in chemotherapy and impact on the management of emesis].
AB  - The treatment of cancer patients has improved over the few past years. The
      improvement includes new chemotherapy modalities and the new treatments for side
      effects. The introduction over the last 5 years of 5-HT3 receptor antagonists, a
      recent class of antiemetic agents, and hematopoietic growth factors, has allowed
      oncologists to improve success rates and survival of cancer patients, by
      developing new cytotoxic agents and increasing drug doses and/or modifying the
      design and administration of conventional chemotherapy treatment schedules. At
      present, dose-intensifications of several cytotoxic agents are available.
      Pharmacomodulation with 5 FU and folinic acid is more emetogenic than 5 FU alone.
      In contrast, chronomodulation seems to be less emetogenic. For new cytotoxic
      agents and oral chemotherapy, the emetogenic potential differs according to the
      drug and the antiemetic treatment must be therefore adapted to each situation.

PMID- 8745676
TI  - [Association between testicular germinal tumor and Hodgkin disease].
AB  - We report the case of a patient who presented a Hodgkin's disease of nodular
      sclerosis type twelve years after a non seminomatous germinal testicular tumor
      treated by association of chemotherapy and radiotherapy. Review of literature
      found 19 cases of this association. The etiologic hypotheses able to explain the
      occurrence of these two neoplasms in the same patient are discussed.

PMID- 8745677
TI  - ["Science", medicine and human sciences].

PMID- 8745678
TI  - [Necrotic angiodermatitis: treatment by early cutaneous grafts].
AB  - INTRODUCTION: Necrotic angiodermitis is an uncommonly hypertensive ischemic
      ulceration. It usually occurs on the legs in elderly, hypertensive and sometimes
      diabetic patients. Its extensive and highly painful nature is characteristic.
      Currently, there is no simple effective treatment which is known to stop the
      development. We report the results of a patch graft method applied early before
      the angiodermitis develops into an advanced stage. PATIENTS AND METHODS: The
      technique was used in 13 consecutive patients with 16 episodes of necrotic
      angiodermitis. The graft was made 8 days (mean) after hospitalization. RESULTS:
      The analgesic effect of the graft was apparent within the first days after the
      graft. The violet halo of extension disappeared a mean of 8 days after the graft.
      A second or even third graft was required in 8 of 16 episodes. Total
      cicatrization was obtained after a mean delay of 33 days. CONCLUSION: Patch graft
      is a simple, low-cost, non invasive treatment which can be performed at the
      bedside and even in an outpatient clinic. This stops the extension of the
      necrotic angiodermitis and controls pain. Delay to cicatrization is shorter. The
      favourable effect of the graft could possibly be mediated by vasodilator peptides
      liberated by the graft tissue which would counteract the hypothetical vasospasm.

PMID- 8745679
TI  - [Balanitis and infectious agents. A prospective study of 100 cases].
AB  - INTRODUCTION: The aim of this study was: 1) to evaluate the rate of micro
      organism isolation in 100 patients consulting for balanitis at the Centre of
      sexually transmitted diseases at the St. Louis Hospital in Paris in comparison
      with that of micro-organisms isolated in 60 men without balanitis; 2) to search
      for a possible correlation between the clinical aspect of the disease and the
      nature of the infectious agent identified. METHODS: One hundred consecutive
      patients were included in the study. All underwent a clinical examination and
      samples were taken for bacteriology, mycology and virology examinations. Sixty
      healthy volunteers served as controls. Two samples were taken from the
      balanopreputial groove in search for fungi and bacteria. RESULTS: Candida
      albicans (CA) was isolated in 33 p. 100 of the patients. A pathogenic bacteria
      (beta-haemolytic streptococci, Staphylococcus aureus, Klebsiella), or a
      potentially pathogenic germ (Haemophilus parainfluenzae, anaerobic bacteria,
      Gardnerella vaginalis, Streptococcus milleri, group HB5) was found without CA in
      28 p. 100 of the cases, a commensal flora (enterobacteria, group D streptococci)
      was found without CA in 8 p. 100 and in 31 p. 100 of the cases non causal agent
      could be identified. DISCUSSION: This series confirms the non-pathogenic nature
      of commensal bacteria: the number of isolations was similar in the subjects with
      and without balanitis (p < 0.9). The role played by the other bacteria in the
      development of balanitis is discussed: saprophytic association or direct
      pathogenesis? The significant difference in the rate of bacteria isolations in
      patients with balanitis compared with controls (p < 0.001) is in favour of a
      pathogenic role. The clinical presentation was not predictive of the presence of
      any particular micro-organism excepting the presence of pustules which were
      highly suggestive of candidiasis.

PMID- 8745680
TI  - [Prevalence of longitudinal melanonychia in the white population].
AB  - OBJECTIVES: The aim of this study was to determine the prevalence of longitudinal
      melanonychia (ML) in white subjects in order to obtain epidemiological data
      suggesting management strategies. PATIENTS AND METHODS: We included 99
      hospitalized patients in this study, all were examined by a dermatologist.
      Another 4,400 healthy subjects were examined by a general practitioner. Criteria
      retained were age, sex, the presence or not of ML, the localization, number of
      bands, intensity of the coloration and size. RESULTS: The prevalence of ML was
      12.6 +/- 3.4 p. 100 (CI 5.9-19.3) and 1.4 +/- 0.18 p. 100 (CI 1.3-1.75)
      respectively in the 99 and 4,400 subjects. The percentage of subjects increased
      progressively with age, particularly after 45 years and reached a peak between 56
      and 65 years. The age distribution was identical. The most frequent localization
      was the thumb, followed by the great toe and the index. None of the ML observed
      had a clinical presentation suggestive of melanoma and no biopsies were taken.
      CONCLUSION: The frequency of melanonychia is thus higher in this series than that
      reported by previous studies where less than 1 p. 100 of the subjects had
      melanonychia. It was highest between the ages of 45 and 65 years. These results
      should be used when counselling patients and proposing systematic exeresis of ML
      above the age of 45 years.

PMID- 8745681
TI  - [Perforating verruciform collagenoma, an exogenous inclusion skin disease?
      Apropos of a case induced by calcium chloride].
AB  - INTRODUCTION: Perforating verruciform collagenoma, first described in 1963,
      designates papular and keratotic post-trauma lesions which show an aspect of
      epidermal perforation microscopically with large fragments of collagen issuing
      through fistulous chimneys, more or less pycnotic polynuclears and squamating or
      necrotic epidermal cells. Three publications have presented this diagnosis. CASE
      REPORT: We observed a patient with multiple lesions with macroscopic and
      microscopic presentations suggestive of perforating verruciform collagenoma. The
      lesions appeared after scratches and inoculation with calcium chloride.
      DISCUSSION: This case is similar to those observed after intradermal inoculation
      of calcium salts. In the 4 previous cases, perforating verruciform collagenoma
      was associated with trauma allowing the intradermal penetration of a particular
      foreign material (glass wool, vegetable debris, drugs or intravenous injections,
      wound caused by a metallic garbage bin). The exceptional nature of perforating
      verruciform collagenoma in highly frequent skin wounds would suggest that a very
      particular post-trauma process is occurring caused by the introduction of an
      exogenous substance within the derma: calcium chloride in our case, a non
      specific material in the four previous cases.

PMID- 8745682
TI  - [Conjugal mycosis fungoides].
AB  - INTRODUCTION: The pathophysiology of mycosis fungoides remains uncertain but HTLV
      I or a similar virus could be involved. We observed a couple who developed
      mycosis fungoides suggesting the infectious hypothesis might indeed be valid.
      CASE REPORT: A 70-year-old man who had often travelled in foreign countries
      developed parapsoriasis en plaques, lymphomatoid papulosis and mycosis fungoides
      successively over a thirty year period. Several years after the first
      manifestation of mycosis fungoides, his wife also developed a single plaque of
      mycosis fungoides. The diagnosis was confirmed on pathology slides and
      immunohistochemistry tests as well as on the basis of T-receptor gene
      rearrangement in both patients. Search for HTLV I was negative using serology
      tests and PCR on circulating lymphocytes. COMMENTS: The epidemiological situation
      in our observation (several trips in foreign countries and the delayed
      development of mycosis fungoides in the wife) favours the hypothesis of an
      infectious mechanism. Search for HTLV I was unsuccessful with classical virology
      methods. Certain recent work suggests a virus similar but different from the HTLV
      I virus could be involved in the pathogenesis of mycosis fungoides.

PMID- 8745683
TI  - [Cosmetic dermopigmentation. The pigment stays ... as do regrets].
AB  - INTRODUCTION: Cosmetic dermopigmentation designates tattooing of the superficial
      derma with pigments in order to obtain an aesthetic effect. We observed two cases
      illustrating the inconveniences of this technique. CASE REPORTS: Two women
      underwent dermopigmentation on the face in a beauty institution to create pseudo
      freckles. Definite macular hyperpigmentation occurred with dyschromia in both
      subjects. COMMENTS: There is a major risk in subjects who undertake
      dermopigmentation of freckles and/or naevus, a practice which should be
      discouraged by dermatologists.

PMID- 8745684
TI  - [Exclusive nodular plexiform neurofibroma. An unusual case of neurofibromatosis
      type 1].
AB  - INTRODUCTION: Type 1 neurofibromatous tumours (NF) are benign skin tumours which
      include cutaneous, subcutaneous and plexiform neurofibromas. Plexiform
      neurofibromas are either diffuse or nodular, the latter form being much more
      frequent. CASE REPORT: We observed a particular form of neurofibroma in an 18
      year-old patient who developed large deep subcutaneous which histology
      examination revealed to be exclusively nodular plexiform neurofibromas. The
      patient also had 6 cafe au lait spots leading to the diagnosis of sporadic NF 1.
      He did not have acoustic neuronoma, schwannoma or posterior cataract, eliminating
      NF 2. COMMENTS: In NF 1, subcutaneous neurofibromas develop in 5 p. 100 of the
      patients. These lesions are termed nodular plexiform neurofibromas when they form
      long formations along nerve branches. The exclusive nature of the nodular
      plexiform neurofibromas in our case was exceptional. It could be hypothesized
      that the particular phenotype in our patient might correspond to a particular
      anomaly of the NF 1 gene.

PMID- 8745685
TI  - [Hydroxychloroquine-puvatherapy photoinduced acute generalized exanthematous
      pustulosis].
AB  - INTRODUCTION: Acute generalized exanthematous pustulosis usually occurs as a
      typical skin reaction to drugs. We observed a case with a photodistribution
      induced by hydroxychloroquine and/or PUVA. CASE REPORT: A male subject had been
      treated for actinic pseudolymphoma since 1988. General corticosteroids had been
      given initially and were followed by PUVA and azathioprine. A new episode with
      erythema involving the trunk and the proximal portion of the limbs was treated
      with corticosteroids and hydroxychloroquine. The symptomatology regressed but
      pustular erythema developed in exposed areas two days after a PUVA session on the
      upper part of the body. The eruption did not involve the zones of the phototests
      one month earlier. The lesions resolved rapidly after withdrawal of
      hydroxychloroquine and PUVA. DISCUSSION: Photo-induced acute generalized
      exanthematous pustulosis with a photodistribution has not been reported
      previously. The imputability of hydroxychloroquine and PUVA, and their
      association is suggested. The appearance of pustular lesion on exposed areas and
      the protection resulting from the phototests would lead to several hypotheses.
      General corticosteroids were ineffective in preventing and in treating acute
      generalized exanthematous pustulosis.

PMID- 8745686
TI  - [Autochthonal leprosy].
AB  - INTRODUCTION: In continental France, Hansen's disease is now a strictly imported
      disease. Native contamination is rare since the foyers described early in the
      century have totally disappeared. CASE REPORT: A case of locally acquired diffuse
      lepromatous Hansen's disease was observed in a patient who developed acrocyanosis
      with distal necrosis over a period of several years. Late cutaneomucal signs led
      to the diagnosis of Hansen's disease after eliminating sarcoidosis and
      tuberculosis. Skin biopsy with Ziehl stain confirmed the lepromatous nature of
      the disease. In addition the patient had undergone splenectomy following trauma
      and also developed babesiasis (a rare protozoan disease in Europe--15 cases
      reported--similar to Texas fever). DISCUSSION: The source of infection in this
      case of Hansen's disease was not found. As in the other cases reported in the
      literature, late diagnosis due to lack of any suggestive context allowed the
      disease to develop into an advanced stage.

PMID- 8745687
TI  - [Melkersson-Rosenthal syndrome treated by thalidomide. 2 cases].
AB  - INTRODUCTION: Treatment of Melkersson-Rosenthal syndrome (MRS) remains uncertain.
      Two cases of MRS treated with thalidomide are described. CASE REPORT: Two
      patients with cheilitis granulomatosa and recurrent facial edema have been
      treated with thalidomide (100 mg daily) for 3 and 6 months respectively. The
      efficacy of thalidomide was complete clinically and histologically in one case.
      In the second one, thalidomide suppressed attacks of facial edema and reduced lip
      swelling. COMMENTS: These cases suggest a therapeutic effect of thalidomide in
      MRS.

PMID- 8745688
TI  - [Congenital spontaneously regressive cutaneous Langerhans cell histiocytosis with
      bone involvement (eosinophilic granuloma)].
AB  - INTRODUCTION: The classification of Langerhans' cell histiocytosis into 5 forms
      does not cover all types of clinical presentations. We observed a patient with
      inborn Langerhans' cell histiocytosis involving the skin and bone tissue. The
      clinical course was benign during the first two years of the patient's life. CASE
      REPORT: Skin lesions noted at birth resolved spontaneously but recurred twice in
      a more benign form. Histology examination showed "band" infiltration of the
      papillary derma composed of Langerhans' cells in direct contact with the basal
      epidermal layer and a few eosinophils. Immunolabelling was intensely positive for
      protein S100 confirming the diagnosis of Langerhans' cell histiocytosis.
      Extension was limited to a lytic lesion in the lower part of the left tibia which
      was treated by curettage. DISCUSSION: In our opinion, Langerhans' cell
      histiocytosis covers a wide range of clinical presentations. Our case was
      remarkable because of the benign course despite its congenital nature and
      dissemination to skin and bone. Prolonged surveillance of Langerhans' cell
      histiocytosis is required for patients without any apparent prognosis factors.

PMID- 8745689
TI  - [Hepato-erythropoietic porphyria].
AB  - INTRODUCTION: Hepatoerythropoietic porphyria is a rare congenital form of
      porphyria with a biochemical pattern of porphyria cutanea tarda. The disease is
      caused by defect in uroporphyrinogen decarboxylase. CASE REPORT: A 3-year-old
      girl was born to healthy consanguineous parents. From birth she had bloody urine
      and developed photosensitivity with bullae at 1 year of age. Clinical examination
      revealed scars resulting from bullae, hypertrichosis of the face and members and
      abnormal pigmentation. Uroporphyrin and coproporphyrin levels in the urine and
      erythrocyte protoporphyrin level were elevated. Uroporphyrinogen decarboxylase
      activity was 37.5 p. 100 of the control, and was 82.5 p. 100 in the mother and
      normal in the father. DISCUSSION: This case of uroporphyrinogen decarboxylase
      deficiency in a child and her parents was not as severe as reported in other
      cases in the literature, confirming the heterogenous nature of
      hepatoerythropoietic porphyria. It is possible that in this case, the mutation
      was different than in previous cases.

PMID- 8745690
TI  - [Weary hereditary sclerosing poikiloderma].
AB  - INTRODUCTION: Hereditary sclerosing poikiloderma is a genodermatosis with
      dominant autosomal transmission and variable penetration. The first case was
      described by Weary in 1969 in 7 members of two black families. CASE REPORT: A 10
      year-old girl had localized regional poikiloderma of the fingers and club toes.
      These lesions were associated secondarily with linear symmetric bands of
      sclerotic tissue in the axiallary regions. On the X-ray examinations of the
      distal phalanges of the fingers and the toes showed a proximal growth foyer and
      absent ungueal phalanges, excepting in the fourth finger of the left hand.
      Capillaroscopy of the supra-ungueal fold of the fingers showed abnormal capillary
      circulation. Histology and ultrastructural examinations did not reveal any
      pathognomonic alterations. DISCUSSION: This case is the first reported in a white
      patient. The radiological aspect and the results of the capillaroscopy of the
      fingers and the toes have not been reported previously in this rare
      genodermatosis. Inheritance of this genodermatosis is poorly defined.

PMID- 8745691
TI  - [A case for diagnosis: tuberculous lupus of the nose].

PMID- 8745692
TI  - [A case for diagnosis: Melkersson-Rosenthal syndrome].

PMID- 8745693
TI  - [Techniques of melanocyte graft].

PMID- 8745694
TI  - [Macrophage activation syndrome. Cutaneous manifestations].

PMID- 8745695
TI  - [Is there any indication for sedatives in dermatology?].

PMID- 8745696
TI  - [Definition of normal criteria of provoked otoacoustic emission in the newborn
      infant].
AB  - Evoked otoacoustic emissions (EOE) were recorded with ILO88 in a group of 254
      neonates (n = 508 ears) in order to determine the normative data. In this study,
      it was found that: (i) the mean EOE amplitude was 20.2 dB SPL, (ii) the EOE
      amplitude of the right ear was significantly higher than those of the left ear,
      (iii) the mean time necessary to record EOE in both ears was around three
      minutes, and (iv) EOE spectrum was large (mean = 638-5,611 Hertz). These data
      permit to precise the clinical interest of EOE for screening auditory function in
      neonates.

PMID- 8745697
TI  - [Malignant tumors of the petrous bone. Apropos of 25 cases].
AB  - Twenty five cases of malignant tumors of the petrous bone are presented.
      Prognosis depends on the histology and on the local invasion which dictate the
      possibility of curative surgery. Squamous cell carcinoma of the middle ear and
      other invasive tumors have a bad prognosis, and in spite of the progress of
      modern image technology, the peripetrous extension of the tumors are often
      underestimated. Actuarial two years survival for squamous cell carcinoma was 38%.
      Total excision needs at least a subtotal petrous resection with, in some cases
      meningal and internal carotid resection. In all cases, surgery was followed by
      radiation. Low grade malignant tumors had a better prognosis and required a more
      limited resection. In these cases, when necessary, facial nerve can be repaired
      by a cable graft at the time of initial surgery.

PMID- 8745698
TI  - [Contribution and role of the scanner in the preoperative evaluation of chronic
      otitis. Radiosurgical correlation apropos of 85 cases].
AB  - High resolution computed tomography (CT) is today the best imaging to study
      chronic middle ear diseases. In a retrospective analysis of 85 chronic otitis
      media (cholesteatoma or not), the authors emphazise the diagnostic value of CT
      scan, its preoperative's role and the radiologic imaging of cholesteatoma. In our
      study, the radiosurgical correlation rate is 0.6 regarding positive diagnosis in
      chronic otitis or cholesteatoma. The malleus and incus analysis is correct, but
      stapes is not observed in 40% of cholesteatoma. The correlation of surgical and
      radiographic findings is excellent regarding the scutum, the horizontal
      semicircular canal (> 0.7), the tegmen (= 0.6), bad for the canal of facial nerve
      (< 0.5). The actual extent of chronic otitis media lesions is overestimated by CT
      scan in 70% of cases. The correlation's rate is reliable for epitympanum and
      aditus. To conclude, the preoperative CT is necessary in those cases: closed
      eardrum cholesteatoma, single functional ear, clinical complications and doubtful
      diagnosis.

PMID- 8745699
TI  - [Treatment of velopharyngeal stenosis after pharyngotomy for chronic snoring.
      Apropos of 13 cases].
AB  - Velopharyngeal stenosis is a rare complication of pharyngotomy (UPPP) for chronic
      snoring. Its treatment is hard because of its recidivant feature. The aim of this
      study was to determine a therapeutic strategy accorded to each stenosis from
      clinical and anatomical features of 13 velopharyngeal stenosis. Therapeutic
      behavior was function of patients complains, of the ground (associated chronic
      rhinosinusitis and obstructive sleep apnea) and clinical findings (partial or
      total stenosis, tonsil remainders, short or long residual soft palate). From
      these data, treatment was medical (1 case) or surgical (12 cases), searching
      lateral velopharyngeal mucosa recovery in order to avoid recidive of stenosis.
      This aim needed locoregional mucosal grafts in 4 patients with short soft palate.
      Patients complains were improved in all cases and there was no patient with
      recurrence of stenosis. The best treatment of velopharyngeal stenosis still
      remains a preventive one, by respecting a severe surgical technique during
      pharyngotomy for chronic snoring.

PMID- 8745700
TI  - [Conditions of the remaining thyroid tissue after partial thyroidectomy].
AB  - The authors have realized a retrospective study about 246 patients who underwent
      partial thyroidectomy for a benign nodule or goiter between 1982 and 1991.
      Recurrence was analized with the method of Kaplan-Meier and concerned 11% of the
      patients at 3 years and 30% at 8 years. The statistical analysis showed that only
      patients with postoperative hormonal treatment were at risk of recurrence. This
      treatment was not randomized. Other studied factors (sex, age, type of surgery,
      pathological results, TSH level) are not correlated with recurrence. Surgical
      management is discussed.

PMID- 8745701
TI  - [Malignant histiocytofibroma. Apropos of 3 cases of cervicofacial localization].
AB  - We report 3 cases of head and neck malignant fibrous histiocytoma (MFH). The
      first case is a xanthomatous subtype of the inferior lip with lymph node
      metastasis. The two others cases are storiform-pleomorphic MFM of the hypopharynx
      and Killian area. A summary of actual knowledges about this entity is reviewed.

PMID- 8745702
TI  - [Granular cell tumor localized in the glottis in children. Apropos of a case].
AB  - We report the first case of adult granular cell tumor form localized in the
      glottis in a 8 year-old girl. The first symptom was a chronic dysphonia.
      Examination with rigid optic demonstrated an irregular yellow hypertrophic lesion
      in the posterior third of the left vocal fold. The lesion was removed by CO2
      laser micro-spot under general anesthesia. There has been no recurrence after 15
      months of follow-up and the postoperative voice quality is satisfactory regarded
      both objectively as subjectively. Granular cell tumors are rare. The histogenesis
      is still badly known. Enzymological and electron microscopy studies seem to
      indicate a nervous origin (Schwann cells). Treatment is surgical. Wide local
      excision is the general rule for limited lesions with easy access. When bigger
      lesions are present in more vital structures such as trachea or oesophagus,
      surgery has to be more cautious.

PMID- 8745703
TI  - [Hemangiopericytoma with parotid localization. Apropos of a case].
AB  - The localisation of hemangiopericytoma in the parotid gland is rarely seen. The
      anatomo-clinic diagnosis is sometimes difficult, this tumor keeps a prognosis
      generally uncertain. The autors mean to study through one observation of the
      location of the hemangiopericytoma in the parotid gland, the modality of
      therapeutic, diagnosis and evolutionary of these tumors.

PMID- 8745704
TI  - [Closure of esotracheal fistula after phonation implants. Technique and results
      of tracheal ascension].
AB  - Enlarging tracheoesophageal fistula after tracheoesophageal prosthesis for voice
      rehabilitation remains a major challenge. The authors analyze the results of
      treatment of 15 severe enlarging tracheoesophageal fistulas among 28 cases (52%)
      of tracheoesophageal voice rehabilitation which occurred during a 4 years period
      of time. Among these 15 cases, a spontaneous closure occurred in 3 cases (20%), a
      two layers closure was performed in 4 cases (26%) and a closure using a tracheal
      ascension associated with the design of a new tracheostoma was performed on 8
      cases (53%). The authors describe the surgical technique and discussed the
      advantages of surch technique.

PMID- 8745705
TI  - [Retinal detachment after posterior capsulotomy with YAG laser].
AB  - BASIS: We studied retinal detachment following YAG laser capsulotomy, to
      determine risk factors, semiology, management, and prognosis. Material and
      methods During a period of six years, we observed 24 cases: group A: 19 patients
      aged between 41 and 75 years (19 eyes); group B: 3 patients aged less than 25
      years (5 eyes). RESULTS: The mean time interval between posterior capsulotomy and
      diagnosis of retinal detachment was 14 months for group A, 21 months for group B.
      The patients in group B presented a clear tendancy to bilateralization. Retinal
      detachment was total or subtotal in 25% of the cases. The macula was detached in
      58%. We could not identify any retinal lesion in 16% and found suspect zones with
      no clear evidence of dehiscence in 17%. Anatomic success was achieved in 88% of
      the cases. The proliferative vitreoretinopathy was the main cause of recurrence.
      Mean visual acuity of the patients who had a re-attached retina was 4.9/10.
      Seventy-three per cent of the patients recovered a visual acuity > or = 4/10.
      CONCLUSION: The clinical characteristics of the post-YAG retinal detachment did
      not differ from those seen in pseudophakic eyes. Some process may reduce the
      incidence and improve the prognosis of this type of retinal detachment. Retinal
      detachment. Retinal detachment in young adults. YAG laser.

PMID- 8745706
TI  - [Non-refractive complications of keratectomy with Excimer laser in 141 myopic
      eyes].
AB  - PURPOSE: The purpose of this study is to evaluate the safety of myopic
      photorefractive keratectomy and to study the frequency of complications, excepted
      refractive problems. METHODS: A consecutive series of 170 eyes has been studied
      in a prospective trial low-up of one year for 107 eyes and six months for 34
      eyes. Twenty-nine eyes have been lost. RESULTS: The main complication after six
      months is the loss of the best spectacle-corrected visual acuity. It was due to a
      haze in seven eyes (loss of one line in five eyes and four lines in one eye) and
      to an excentric ablation in three eyes (one line in two eyes and two lines in one
      eye), results found for treatments of six diopters or more. The haze is a
      constant complication. A direct relationship between the haze's intensity and the
      treatment importance was found as was an inverse relationship between the
      patient's age and the haze's intensity. The excentric ablations have no influence
      on the final visual acuity when they concern less than one millimeter. The
      epithelial problems were always of less importance. CONCLUSION: Except in
      corrections greater than seven diopters, complications are uncommon after Excimer
      for myopia. Patient's information has to be rigorous.

PMID- 8745707
TI  - [Clinical and psychological factors influencing the efficacy of botulinum toxin
      in the treatment of hemifacial spasm and blepharospasm].
AB  - We analyzed the influence of clinical and psychological factors on the long-term
      efficacy of botulinum toxin A (BTX) injections in 45 patients with blepharospasm
      and 66 patients with hemifacial spasm. Injections efficacy (respectively 94.3%
      and 95.7%) and duration of relief (respectively 14.8 and 18.7 weeks) remained
      stable over seven successive injections. Clinical improvement was not influenced
      by patients' sex, age, or disease duration but by psychological background (p <
      0.001). Patients who failed to respond after repetitive injections had lower
      inter-injections intervals (p < 0.05). This data shows: (1) the importance of
      psychological contexte in subjective evaluation of treatment efficacy with BTX,
      (2) emphasizes the necessity of avoiding close injections.

PMID- 8745708
TI  - [Retinal vein occlusion and resistance to activated protein C].
AB  - BACKGROUND: A new abnormality in the coagulation system, the resistance to
      activated protein C, has appeared among the numerous hereditary modifications
      which predispose patients to deep-vein thrombosis. The molecular abnormality
      responsible for the resistance to activated protein C is due to a mutation of an
      amino acid in the 506 position (Arg-->Gln) at the level of the factor V,
      designated under the name of factor V Leiden. METHODS: The authors wished to
      search for this alteration of the haemostasis in 106 patients with retinal venous
      occlusion hospitalized in Centre Hospitalier National d'Ophthalmologie des Quinze
      Vingts (Paris). RESULTS: In our study of 106 patients presenting a retinal venous
      occlusion, the resistance to activated protein C was the most frequent
      coagulation abnormality found (4.71%), when compared with the other deficits of
      the inhibitors of the clotting system: protein S (2.80%), antithrombin III
      (0.94%) et protein C (0%). CONCLUSION: The test of resistance to activated
      protein C should be recommanded in cases of retinal venous occlusion,
      particularly in the search for a cause of thrombosis in young patients or in
      recurrent thrombosis.

PMID- 8745709
TI  - [Dacryocystography using CT and MRI. Comparative study apropos of 13 clinical
      cases].
AB  - Magnetic Resonance Imaging of a dacryocystography and a watersoluble computed
      tomographic dacryocystography were compared in 13 prospective cases after facial
      traumas, infections or without previous history. All had either watering eyes,
      ephiphora or dacryocystitis. This study demonstrated the superiority of computed
      tomography which must be used in first intention for complexe problems of the
      lacrimal drainage system. Only tumoral pathology (very rare) requires Magnetic
      Resonance Imaging. Combined computed tomography and dacryocystography in the same
      time provide diagnostic precision and less radiation. Confortable for the patient
      by helicoidal acquisition, computed tomography is cheaper than a Magnetic
      Resonance Imaging.

PMID- 8745710
TI  - [Isolated oculomotor palsy disclosing multiple myeloma].
AB  - Two cases of oculomotor nerves involvement as uncommon initial manifestation of a
      parasellar extramedullary plasmacytoma are reported. The first patient presented
      with an isolated left VI cranial nerve palsy; the second one had an incomplete
      left III cranial nerve palsy. In both cases clinical investigation and computed
      tomography revealed an intracranial plasmacytoma associated with multiple
      myeloma. It is important to underline the difference between an intracranial
      extramedullary plasmacytoma and a plasmacytoma associated with multiple myeloma.
      In fact the absence of a general associated illness should show a most favourable
      course.

PMID- 8745711
TI  - [Acute retinal necrosis syndrome. Retrospective study apropos of 14 eyes in 11
      patients].
AB  - PURPOSE: The authors present a retrospective study of fourteen eyes of eleven
      patients suffering from acute retinal necrosis syndrome (ARN) and compare the
      results with previously published data. MATERIAL AND METHODS: All patients were
      referred to us between 1985 and 1993. The results of initial examination, the
      epidemiological and aetiologic data, as well as the clinical course and treatment
      are summarized in two tables. RESULTS: First clinical examination found a
      prominent ocular inflammatory reaction, several sites of peripheral retinal
      necrosis and one retinal vasculopathy. Bilateralisation occurred in 28% of the
      patients. An optic neuropathy developed in 57% of the cases, and a retinal
      detachment in 78%. Initial examination and data on the clinical course are
      discussed and compared with those described in the literature. CONCLUSION: The
      results of the current study are representative of the various clinical and
      biological profiles of acute retinal necrosis and are similar to those described
      in previous publications. Earlier care in specialized departments of
      ophthalmology should allow a better anatomical and functional prognosis in the
      future.

PMID- 8745712
TI  - [Periarteritis nodosa with initial ocular involvement].
AB  - Biopsy documented polyarteritis nodosa in a patient who initially presented with
      ocular involvement. Although uncomun, a wide variety of ocular manifestations can
      be seen in polyarteritis nodosa. In this case, bilateral choroidal vasculitis was
      documented, first in the left eye, and one year later, in the right eye. The
      condition appears to be an acute posterior multifocal placoid pigment
      epitheliopathy in the left eye. In the fellow eye, serpiginous choroiditis-like
      lesions were observed.

PMID- 8745713
TI  - [Bilateral choroidal metastases of pancreatic carcinoma].
AB  - Pancreatic adenocarcinoma represents 2 to 5% of all the carcinomas. It is the
      fourth largest cause of death from cancer. It gives rise to metastasis of the
      liver, kidney, brain, etc. But choroidal metastasis are infrequent. We present
      the case of a male aged 45 years, who presented bilateral choroidal metastasis of
      pancreatic carcinoma.

PMID- 8745714
TI  - [Acute retinal necrosis syndrome].

PMID- 8745715
TI  - [In vitro changes induced by phenylmercury nitrate on fungi causing keratitis.
      Scanning electron microscopy study].
AB  - Antifungal activity of phenylmercury nitrate was studied on fungi from keratitis.
      Important deterioration and bursting were observed with 2 mg/100 ml phenylmercury
      nitrate concentration on Aspergillus flavus, Scedosporium and Candida albicans
      spores.

PMID- 8745716
TI  - [Juvenile glaucoma].

PMID- 8745717
TI  - [Arteriosclerosis and osteoporosis].
AB  - A certain number of elements suggest a link between arteriosclerosis and
      osteoporosis. Generally, osteoporosis in women is considered to result from
      altered secretion of sexual hormones after menopause and in elderly subjects from
      hyperparathyroidism secondary to calcium and vitamin D deficiency. As for the
      heart, the brain, the kidney or muscle, bone tissue could also be altered by
      vascular aging and arteriosclerosis. Large epidemiological studies have
      demonstrated a relationship between bone mineral density, measured by
      monophotonic absorptiometry and mortality due to cerebral vascular events.
      Several hypotheses have been proposed to explain this relationship including
      lower endogenous estrogen levels and arteriosclerosis of the renal vessels
      favoring perturbed vitamin D metabolism. Arteriosclerosis could also have a
      direct effect on bone tissue via an ischemic mechanism. The pathophysiolojical
      mechanisms are not fully understood, but could involve hormone and cytokine
      dependent bone remodeling and the complementary actions of bone tissue and the
      hematopoietic bone marrow functioning as an unit. Further epidemiological studies
      would be useful to confirm the relationship between arteriosclerosis and
      osteoporosis. The efficacy of vasodilator drugs on osteoporosis could be tested
      and histology and immunochemical studies could help in our understanding of the
      effect of ischemia on bone metabolism.

PMID- 8745718
TI  - [Transfusion strategy in programmed hemorrhagic orthopedic surgery].
AB  - OBJECTIVES: Prospectively assess autologous blood transfusion for programmed
      orthopedic procedures. METHODS: From January 1 to December 31 1993, 307 patients
      underwent programmed orthopedic procedures: total hip replacement (n = 191),
      total knee replacement (n = 83) and osteotomy (n = 33). General (94%) or spinal
      anesthesia (6%) was used. The anesthesist explained transfusion techniques and
      patients gave informed consent for inclusion in an autologous transfusion
      protocol including differed autologous transfusion, intentional normovolemic
      hemodilution and intraoperative transfusion of shed blood. RESULTS: A total of
      269 autologous transfusion were performed among the 307 patients (87.6%). This
      was sufficient in 242 cases (78.8%) and in 65 (21.2%) homologous transfusion was
      required. Among the 269 patients given autologous transfusion, differed
      transfusion was used in 145 (53.9%), intentional normovolemic hemodilution in 124
      (46%) and intraoperative transfusion of shed blood in 222 (82.5%). Among the
      patients given a differed autologous transfusion, 9 (6.2%) required a homologous
      transfusion and among the 40 patients in which all 3 techniques were used, only 2
      (5%) received homologous blood, both due to secondary complications. CONCLUSION:
      These findings show that when differed autologous transfusion is included in the
      transfusion strategy, less than 10% of the patients require homologous blood. In
      addition, when the 3 autologous transfusion techniques are used, the rate of
      homologous blood transfusion approaches zero.

PMID- 8745719
TI  - [Procollagen III and laminin in chronic viral hepatopathies].
AB  - OBJECTIVES: We measured serum concentrations of the N-terminal peptide of type
      III procollagen (PIIIP) and laminin (Lam-P1) in patients with chronic viral liver
      disease in the various stages of the clinical course, to judge their value in
      assessing liver fibrogenesis, and also compared them with a number of liver
      function tests and histological scores of inflammation and fibrosis. METHODS:
      Twenty-nine patients with chronic persistent hepatitis, 39 with chronic active
      hepatitis and 42 with liver cirrhosis were studied. The control group was
      composed of 45 healthy blood donors. Serum PIIIP and Lamp-P1 were determined by
      radioimmunoassay; hepatic function was measured by routine assay; liver fibrosis
      and inflammation were graded on a 0-3 score scale. RESULTS: A significantly
      higher increase in serum levels of PIIIP and Lam-P1 was found in the liver
      cirrhosis group compared with the other groups (p < 0.05). Serum PIIIP correlated
      with transaminase levels in the chronic active hepatitis group and with
      gammaglobulin and total bilirubin in the liver cirrhosis group. A positive
      correlation was found only with gammaglobulin and total bilirubin in the
      cirrhosis group. A positive correlation was found between serum PIIIP levels and
      the rating scale of liver necrosis. In contrast, for Lam-P1 values, a correlation
      with the rating scale of necrosis and fibrosis was found. CONCLUSION: Our
      findings confirmed the increase of PIIIP and Lamp-P1 in chronic viral liver
      disease, but because of the frequent overlap values, they cannot be used as
      substitutes for liver biopsy for diagnosis. The correlations with the
      histological findings indicate that these two markers can be used during the
      follow-up of patients receiving anti-inflammatory or anti-fibrotic treatment.

PMID- 8745720
TI  - [Treatment of metastatic carcinoid tumors with interferon-alpha. Five cases].
AB  - OBJECTIVE: Interferon has been proposed in treatment of metastatic carcinoid
      tumours with varied results. METHOD: Five patients with metastatic carcinoid
      tumours were treated for 1 year with rIFN alpha 2b at a dose of 5 MU. three times
      a week during the first month and 10 MU. three times a week during the following
      months. Carcinoid syndrome was present in all cases. RESULTS: Clinical response
      with improvement of diarrhoea and flushs was obtained in all cases. Urinary
      excretion of 5 HIAA and blood serotonin were reduced in 2/5 and 4/5 patients
      respectively. IFN treatment led to a stabilization of the metastatic tumour in
      all cases. Recurrence of symptoms was observed within three months following the
      end of the IFN treatment. CONCLUSION: These findings confirm the contribution of
      IFN in the treatment of metastatic carcinoid tumours.

PMID- 8745721
TI  - [Mega-esophagus: treatment by celioscopic approach].
AB  - Heller's procedure is widely used as the most appropriate method for treating
      achalasia. We performed the procedure laparoscopically in three patients with
      good results. Two females and one male, age 40, 60 and 68 years, presented with
      long-term recurrent dysphagia due to achalasia which did not respond to
      endoscopic dilatation. Heller's procedure was performed laparoscopically in all
      three with no particular difficulty. In our cases we also attached the anterior
      border of the greater curvature to the left side of the myotomy and fixed it to
      the right diaphragmatic pillar to reduce reflux. The procedure would appear to
      have less risks than laparotomy since visualization of the operative fields is
      better. Laparoscopy will undoubtedly become the preferred procedure for
      achalasia.

PMID- 8745722
TI  - [Physiopathology of symptoms of malaria. Role of cytokines, cytoadherence and
      premunition].
AB  - Clinical symptoms of malaria are caused by a cascade of events triggered by the
      release of parasite "toxins" at the time of schizont rupture. The production of
      cytokines, particularly TNF alpha, plays a central role in this cascade. In
      addition to TNF, the pathogenesis of cerebral malaria (the most severe form of
      the disease) also requires the existence of cytoadherence of infected
      erythrocytes in cerebral capillaries and the intensity of this cytoadherence is
      controlled by a mixture of host and parasite features. Finally, anti-parasite and
      anti-toxic immunity (or "premunition") play a role in the reduction of pathology
      in individuals living in endemic areas.

PMID- 8745723
TI  - [Human immunodeficiency virus infection in pregnancy. General aspects].
AB  - Seroprevalence of HIV infection in pregnancy is on the increase worldwide.
      Approximately 10 million infants will have been infected by the year 2000 and the
      majority of these children will have acquired infection by vertical transmission
      of HIV from infected mothers. Recent reports suggested that pregnancy does not
      accelerate the course of HIV infection. Prospective studies from industrialized
      countries where most women have asymptomatic HIV infection, have not shown an
      association with increased risk of adverse pregnancy outcome. Estimates of the
      rate of vertical transmission range from 15% to 40%.

PMID- 8745724
TI  - [Asymptomatic pulmonary pneumocytosis accidentally discovered in a patient with
      HIV infection].

PMID- 8745725
TI  - [Vaccination against type B Haemophilus influenzae in the Bouches du Rhone
      district. Value and practice].

PMID- 8745726
TI  - [Hemlock poisoning: an occasionally benign course].

PMID- 8745727
TI  - [Benign monomelic amyotrophy and localized spinal atrophy].

PMID- 8745728
TI  - [When should genital actinomycosis be considered?].

PMID- 8745729
TI  - [Infections caused by several Shigella species after returning from Africa].

PMID- 8745731
TI  - [Infections related to central venous catheters. Value of a more anatomical
      approach to the subclavian vein].

PMID- 8745730
TI  - [Consumption coagulopathy in a periprosthetic fracture of the hip].

PMID- 8745732
TI  - [Duodenal perforation caused by a tuna fish bone: late course].

PMID- 8745733
TI  - [Reproducibility of urodynamic tests in patients with spinal cord injuries and
      indwelling catheters].

PMID- 8745734
TI  - [Apropos of laparoscopic autopsy].

PMID- 8745735
TI  - An iron-binding Trypanosoma cruzi urinary antigen.
AB  - An 80-kDa Trypanosoma cruzi urinary antigen (UAg) was affinity-purified from the
      urine of infected dogs. We demonstrated that UAg is structurally and functionally
      related to proteins belonging to the transferrin family, as shown by amino acid
      sequence and iron binding experiments. Nevertheless, monoclonal antibodies raised
      against UAg specifically and selectively recognized this parasite's circulating
      antigen. The existence of an 80-kDa T. cruzi antigen co-migrating with UAg could
      be confirmed when epimastigotes were metabolically labelled with [35S] methionine
      and then immunoprecipitated with the above mentioned antibodies. We conclude that
      UAg is an iron-binding T. cruzi component eliminated in the urine of the infected
      host.

PMID- 8745736
TI  - Effects of iron deficiency on the hepatic development of Plasmodium yoelii.
AB  - Iron deficiency through an iron-deficient diet and through an inactivation of
      hepatic xanthine dehydrogenase (XD) was shown to modulate Plasmodium yoelii
      sporozoite development in hepatocytes. When mice that are on iron-deficient diet
      were challenged with sporozoites, enhancement of hepatic stage development was
      observed, resulting in the earlier appearance of blood parasites. In contrast,
      inhibition of parasite hepatic development was noticed when iron deficiency was
      the result of hepatic XD inactivation. In vitro studies have shown that diet
      induced iron-depletion increases penetration of sporozoites into liver cells
      while inactivation of hepatic XD resulted in an inhibition of both sporozoite
      penetration and schizont maturation. Moreover, inhibition of heme synthesis
      (which requires intrahepatic iron) also led to an inhibition of parasite
      development.

PMID- 8745737
TI  - Investigation of Culicoides (Diptera: Ceratopogonidae) in relation to the
      transmission of bovine Onchocerca and other filariae in central Kyushu, Japan.
AB  - In Kyushu, Japan, where a human case of zoonotic onchocerciasis was found, a
      survey was conducted to know if the bovine Onchocerca species of this region, O.
      gutturosa, O. lienalis and O. sp., which develop in local Simulium spp., were
      also transmitted by Culicoides. A total of 17,006 out of 42,582 females of eight
      Culicoides species captured by light-traps from May to November in 1989 and 1990
      at two cattle sheds, one in Oita and one in Kumamoto, were dissected and examine
      for Onchocerca infection. Overall results showed that none of the species had
      filarial infections except 4 of 946 C. arakawae, an ornithophilic species,
      collected in Oita which harboured filarial larvae with a short tail, belonging to
      Lemdaninae. Unsheathed microfilariae indistinguishable from O. lienalis or O.
      gutturosa were found in the midgut of only one blood-fed C. matsuzawai collected
      in Oita. It is concluded that Culicoides species would not be vectors of these
      three bovine Onchocerca species. Additional collections of Culicoides in a
      residential area of Oita showed that several filarial species, Lemdaninae and
      Splendidofilarinae, probably from birds, are transmitted by C. arakawae.

PMID- 8745738
TI  - The black-backed jackal (Carnivora: Canidae) in Namibia as intermediate host of
      two Sarcocystis species (Protozoa: Sarcocystidae).
AB  - Two structurally different sarcocysts are reported from the black-backed jackal
      (Canis mesomelas) in Namibia by means of light and transmission electron
      microscopy for the first time. They cannot be attributed to any of the hitherto
      described Sarcocystis species from Carnivora, of which the ultrastructure of the
      cyst wall is known.

PMID- 8745739
TI  - [Anisakiasis in the Nantes area. From fishmongers' stalls to medical offices].
AB  - 1,103 fish-fillets belonging to 4 species were examined during one year, during a
      survey conducted among commercial marine fish-fillets in the Nantes area (west
      coast) in France. Anisakis simplex L3 were found in 3 different species and most
      of them are frequently present in coal fish (Pollachius virens) and whiting
      (Merlangius merlangus). We report 6 cases of human anisakiasis (3 certain cases
      and 3 probably cases). Diagnosis was established in 3 cases by microscopic
      analysis of intestin bowel specimens (eosinophilic granulomas and/or parasitic
      fragments) and in 3 cases gastroscopy. Serodiagnosis was positive in 1 case and
      the consumption of undercooked fishes was found in 5 cases. This work emphasizes
      the role of anisakiasis as a source of digestive symptoms and intestinal
      eosinophilic granuloma.

PMID- 8745740
TI  - Clinical and serological observations on experimental infections with Babesia
      canis and its diagnosis using the IFAT.
AB  - Naive Beagle dogs (n = 5) were experimentally inoculated with two stocks of
      Babesia canis. Dogs were examined regularly for parasitaemia and for antibodies,
      using the indirect immunofluorescent antibody test (IFAT). This test proved to be
      useful for the diagnosis of babesiosis. After primo-infection dogs seem to
      develop a certain degree of immunity, although this immunity is neither absolute
      nor of long duration. Treatment of infected dogs with imidocarb (6 mg/kg) cleared
      the infection, but did not prevent the production of IFAT-antibodies. An infected
      dog treated with long acting oxytetracycline (20 mg/kg) became a subclinical,
      chronic carrier of the disease.

PMID- 8745741
TI  - Postprandial lymphatic flux and malaria.
AB  - 24 hours after an intra-peritoneal inoculation of frozen blood infected with
      Plasmodium yoelii nigeriensis, the malarial infection is non detectable in most
      starved mice while it is patent in mice fed 2 hours before the inoculation. It is
      assumed that the post feeding lymphatic flow brings to the blood the latent
      merozoites.

PMID- 8745742
TI  - Two cases of giardiasis unsuccessfully treated by albendazole.

PMID- 8745743
TI  - Spontaneous lesions in the thyroid of sheep and goats in Iran.
AB  - A slaughterhouse survey conducted in Ahwaz (Iran) revealed higher incidence of
      pathological lesions in the thyroid glands of goats (6.54%) than in sheep (2.8%).
      Goitre was found in 4.99% and 1.96% of slaughtered goats and sheep, respectively.
      However, ultimobranchial body cysts were present three times more in sheep than
      in goats.

PMID- 8745744
TI  - Clinico-pathological observations on naturally occurring contagious ecthyma in
      lambs in Saudi Arabia.
AB  - Typical lesions of contagious ecthyma were diagnosed in lambs four months old and
      infection has been confirmed by viral isolation and identification. The lambs had
      lower total serum protein values, haemoglobin concentration, erythrocyte counts
      and packed cell volume, but higher blood leukocyte counts and increased serum
      transaminase activity when compared to apparently healthy animals. The disease is
      believed to be transmitted from newly introduced goats which showed evidence of
      infection.

PMID- 8745745
TI  - [Evaluation of vaccinal protection against rinderpest in Cameroon. II. The North
      province].
AB  - Cameroon joined the sero-survey component of the PARC (Pan African Rinderpest
      Campaign) program in 1989. During the 1992 Campaign, a detailed sampling frame,
      adapted to the breeding conditions of the North Province was drawn up according
      to PARC recommendations. The four administrative divisions of the province were
      covered by sampling cattle in 14 sites chosen by randomisation. Eight thousand
      six hundred and eighty sera samples from 217 cattle herds were tested using
      FAO/IAEA rinderpest competitive ELISA technique. The results indicated an overall
      prevalence of rinderpest virus antibodies (RPVA) of 66%. This is below the target
      objective. The differences of prevalence between age groups and breeding systems
      (sedentary of transhumant) are statistically significant. The same results have
      been reported in the Adamaoua Province (62% in 1991 campaign). These results do
      not reflect the situation in all the country. It is suggested to hold general
      meeting between different livestock managers from the provinces with high cattle
      populations to adopt commun vaccination measures with the target objective of
      increasing the level of immunity.

PMID- 8745746
TI  - A comparative study of the efficiency of a pro-biotic and the anti-K99 and anti
      A14 vaccines in the control of diarrhea in calves in Brazil.
AB  - A total of 99 pregnant cows were divided into eight groups submitted to the
      following treatments: group I (n = 29) consisted of unvaccinated cows whose
      calves did not receive a probiotic and was used as control. Group II (n = 10)
      consisted of vaccinated cows whose calves did not receive a probiotic. Groups
      III, IV and V (n = 10 neach) consisted of vaccinated cows whose calves received a
      probiotic for 5, 15 and 30 days, respectively. Groups VI, VII and VIII (n = 10
      each) consisted of unvaccinated cows whose calves received a probiotic for 5, 15
      and 30 days, respectively. Each animal in the vaccinated groups received two 5.0
      ml vaccine doses containing pili K99 and A14 of Escherichia coli by the
      subcutaneous route. The probiotic containing Lactobacillus acidophilus at the
      dose of 2.0 x 10(8) live cells in 250 ml milk, was administered orally. All
      animals were observed clinically and bacteriologically and anti-K99 and anti-A14
      antibody titers were determined in serum and colostrum. Mean calf weight was
      measured at birth and at 30 days of age. The results showed that a combination of
      the vaccine with the probiotic administered for 15 and 30 days was the most
      efficient treatment for the control of diarrhea.

PMID- 8745747
TI  - [Diagnosis of Babesia bigemina with the immunoperoxydase test].
AB  - An immunoperoxidase assay for the serological diagnosis of Babesia bigemina was
      developed. The antigen slides were prepared from B. bigemina-infected blood and
      stored at -20 degrees C. One hundred and sixty five sera were tested, comparing
      the immunoperoxidase assay to the indirect fluorescent antibody test. A
      coincidence of 95% was observed between both tests. For the immunoperoxidase
      assay, a relative sensitivity of 94.8%, a relative specificity of 95.5%, and a
      positive predictive value of 96.8% were calculated. The results demonstrated the
      efficacy of this technique for detecting antibodies to B. bigemina.

PMID- 8745748
TI  - [Comparison of the sensitivity of the Woo test and a test for detecting antigens
      to Trypanosoma vivax in 2 sheep experimentally infected with a Guyanese strain of
      the parasite].
AB  - A trapping ELISA for the detection of circulating antigens of Trypanosoma vivax
      with a specific monoclonal antibody was developed by Nantulya and Lindqvist in
      1989. With the African strains tested, its sensitivity proved very high. Using
      reagents supplied by ILRI, the sensitivity of this test was compared with that of
      the Woo test in two sheep experimentally infected with a Guyanese strain of T.
      vivax. Blind tests carried out at CIRDES and ILRI confirmed the results obtained
      in French Guiana. The animals were bled regularly during the first 130 and 285
      days of infection. Whatever the period of infection ans whether there was patent
      parasitaemia or not, the mean sensitivity of the ELISA test was very low: 2.1% of
      positive results, far below the Woo test's 54% of positive results. Associating
      the two techniques did not improve the sensitivity. The mean optical densities
      recorded during these long periods of infection (0.010 +/- 0.004 and 0.012 +/-
      0.002) are so close to the sensitivity threshold of the ELISA readers that they
      cannot be proposed as a cut-off threshold to improve the sensitivity of the test.
      A complementary study of the sensitivity of this test is in progress at ILRI. As
      already observed in Burkina Faso and The Gambia, this poor sensitivity may
      greatly affect the results of the epidemiological surveys being carried out with
      these reagents in Africa. New monoclonal antibodies must be developed to produce
      a test for T. vivax antigens with more satisfactory sensitivity.

PMID- 8745749
TI  - Leucocyte and thrombocyte responses in dogs experimentally infected with
      Trypanosoma brucei.
AB  - Three dogs were subcutaneously infected with Trypanosoma brucei strain ILRAD
      1797. Artificial haemolytic anaemia was induced in 2 other dogs by phlebotomy,
      heat treatment and re-infusion of the blood, while 2 dogs were kept as control
      animals. The infected animals developed pan-leucopenia and thrombocytopenia,
      while the dogs with artificial haemolytic anaemia developed leucocytosis and
      thrombocytosis. These findings suggest that there was a bone marrow depressing
      factor in the plasma of T. brucei-infected dogs especially as it affected
      leucocyte production.

PMID- 8745750
TI  - [Haemophilus influenzae infections after bone marrow grafting: from observation
      to prevention].

PMID- 8745751
TI  - [Contribution of bronchoalveolar lavage and transbronchial biopsy to diagnosis
      and prognosis of drug-induced pneumopathies].
AB  - This survey reports on 10 case-studies of drug-induced pneumonitis. The drugs
      under consideration are amiodarone, methotrexate, chlorambucil, sulindac,
      nilutamide-leuproreline, cyclothiazide, with the possible addition of bleomycin.
      In each case, one or more bronchoalveolar lavage were carried out and in most
      cases it was also possible to perform a transbronchoscopic lung biopsy. The
      results of these tests are analysed in order to ascertain their contribution to
      diagnosis and prognosis. Regarding diagnosis, bronchoalveolar lavage does not
      evidence a typical cellular configuration characterizing drug-induced alveolitis.
      Moreover, transbronchoscopic lung biopsy plays no part in diagnosing this
      pathology. Both these tests, however, help to eliminate other hypotheses.
      Regarding prognosis, transbronchoscopic lung biopsy provides no information,
      unlike bronchoalveolar lavage in which a high rate of neutrophils in the lavage
      fluid is sometimes associated with the development of pulmonary fibrosis.

PMID- 8745752
TI  - [Tuberculous adenopathies of the mediastinum: surgical experience in adults].
AB  - Fifty eight patients were treated for mediastinal tuberculous adenopathies in the
      thoracic surgery department from 1986 to 1992. Surgery was diagnostic in 49:
      mediastinoscopy n = 42, left anterior mediastinotomy n = 3, thoracotomy n = 3 and
      video assisted surgery n = 1. Surgery was in view of cure in 9: bronchial fistula
      despite medical treatment n = 6, recurrence under medical treatment n = 3.
      Mediastinal tuberculous adenopathies rarely complicate in adults. Surgical
      treatment is quickly effective in prolonging and complicating cases under medical
      treatment and also probably diminishes the risk of bronchial and pulmonary
      sequellaes.

PMID- 8745753
TI  - [Pulmonary plasmacytoma. Apropos of a case. Review of the literature].
AB  - A 65 old man had a solitary primary pulmonary plasmacytoma. Serum
      immunoelectrophoresis revealed an immunoglobulin G Lambda M-protein. Screening
      for multiple myeloma with bone marrow biopsy and skeletal survey were negative.
      The patient underwent left lower lobectomy associated with resection of
      mediastinal lymph nodes. Immunoperoxydase staining of the mass revealed a
      monoclonal plasma cell population producing IgG, Lambda chains. No adjuvant
      chemotherapy or radiation therapy was performed. In few weeks, the paraprotein
      durably disappeared. Four years later, the patient is well and has no evidence of
      recurrence or myelomatosis. Authors emphasize the rarity of this tumor. The best
      treatment of pulmonary plasmacytoma is discussed.

PMID- 8745754
TI  - [Pulmonary lymphangiomyomatosis: a 3-year follow-up of medroxyprogesterone
      acetate therapy. Apropos of a case].
AB  - A 41-year-old female patient presenting with chylothorax was found to have
      pulmonary lymphangiomyomatosis. Recurrence led to parietal pleurectomy. Lung
      biopsy performed at surgery confirmed the histology diagnosis. Hormone treatment
      with medroxyprogesterone acetate was initiated immediately and administered via
      intramuscular injections each month. The treatment was continued for three years
      and regular clinical, functional and radiologic follow-up provided evidence of
      response: radiologic and functional stability were achieved at the cost of major
      secondary effects of hormone therapy. This rare, apparently hormone-dependent,
      disease raises the problem of the long-term benefit of treatment.

PMID- 8745755
TI  - [Bronchiectasis in hemorrhagic rectocolitis. Apropos of a case].
AB  - Bronchectasis is a rare complication of haemorrhagic rectocolitis, 28 case have
      been reported in the literature. We report a case in a 40-year-old patient who
      presented respiratory signs 13 years after the onset of haemorrhagic
      rectocolitis. The diagnosis was confirmed on the bronchogram showing involvement
      of the lower lobes on the right and the left. Local corticosteroids given by
      inhalation decreased the volume of the expectorations and improved bronchial
      obstruction. Abundant bronchorrhoea is characteristic of bronchectasia in
      haemorrhagic rectocolitis as in primary bronchectasia. Response to inhaled or
      systemic corticosteroids is good.

PMID- 8745756
TI  - [Horton disease of pulmonary localization].
AB  - A case of Horton's disease with interstitial pulmonary involvement is reported.
      Transbronchial biopsy of the lung and biopsy of the temporal artery provided
      evidence of giant cell lesions. Outcome was favourable with general
      corticosteroid therapy with regression of the pulmonary disease.

PMID- 8745757
TI  - [2 rare tracheal cartilage anomalies difficult to be differentiated].

PMID- 8745758
TI  - [Cavitary images and dysphonia in a young woman].

PMID- 8745759
TI  - [A new case of meningococcal pleuro-pneumopathy].

PMID- 8745760
TI  - [Invasive pulmonary aspergillosis and influenza virus infection in patients with
      chronic bronchitis?].

PMID- 8745761
TI  - [Ventilatory assistance in acute decompensation of chronic respiratory
      insufficiency in adults (excluding neuromuscular diseases and weaning). 13th
      Consensus Conference on resuscitation and emergency medicine, Strasbourg, 2
      December 1994].

PMID- 8745762
TI  - [Search for bacterial contamination of the aqueous humor during cataract surgery
      with and without local antibiotic prophylaxis].
AB  - PURPOSE: Bacterial contamination of anterior chamber at the end of cataract
      surgery, was compared between two techniques: extracapsular extraction and
      phacoemulsification. The effectiveness of preoperative antibiotic eyedrops using
      Norfloxacine 0.3% (Chibroxine) was also evaluated. METHOD: The study focused on
      101 patients grouped according to surgical technique and presence of preoperative
      antibiotic eyedrops. Conjunctival sampling was made the day prior the surgery, as
      well as in the operating room, after skin and conjunctival desinfection with
      povidone iodine in all the patients included in the study. Aqueous humour was
      collected at the end of surgery. RESULTS: Eight samples out of 101 were positive
      which represents 7.9% of the cases. In 75% of the cases, the anterior chamber
      aspirate showed a different germ or non-recurrent germ in the second conjunctival
      sample. None of the included patients developed endophthalmitis. The two most
      frequent pathogens were Propionibacterium acnes in 62.5% of the cases, and
      Staphylococcus epidermidis in 50%. Another pathogen was found in a culture
      environment: Micrococcus roseus. In two samples, two different bacteria grew:
      Propionibacterium acnes and Staphylococcus epidermidis. Whatever the surgical
      technique, no statistically significant bacterial contamination was found. There
      was no significant statistical difference between patients who had local
      antibiotic eyedrops and those who did not. CONCLUSION: This study confirms the
      poor reliability of local antibiotic eyedrops to prevent surgical contamination.
      Furthermore performing an anterior chamber aspirate at the end of the surgery for
      risk patients would help the physician identify the pathogens involved in
      endophthalmitis in order to begin antibiotic treatment as soon as possible.

PMID- 8745763
TI  - [An expert system for the diagnosis of intraocular pressure disorders].
AB  - PURPOSE: This expert system (ES) is designed to avoid the four types of diagnosis
      errors: by omission or by confusion both of which may occur when collecting signs
      and symptoms and when analyzed data. This ES uses a thesaurus containing 42
      classical and objective signs and a comprehensive library. For a given case
      report, it provides the practitioner with a positive diagnosis, and if possible,
      one or several etiologies taking into account all the data known about
      intraocular disorders. METHODS: This ES is run on a PC-compatible computer with
      640 KB RAM and without hard drive. The 90 KB program is written in compiled
      Basic. After checking the case record to rule out nonsenses, the logic considers
      every sign of the case record as equivalent. Likewise, in the first stage all
      syndromes are considered of equal likelihood. The syndromic diagnosis is set by
      identification. Comparisons of prevalence interfere, when needed, in a second
      phase, within the framework of etiological diagnosis. RESULTS: When tested on a
      set of 180 cases records combined with 115 cases extracted from the literature
      corresponding to more than 1,900 diaagnoses, this ES yielded 100% correct
      positive and differential diagnoses, thus validating the logial hypotheses.
      Probability of error by omission was less than a 3% and probability of error by
      confusion was well below 0.1%. Besides, the logical analysis shelds light on the
      intellectual mechanisms of diagnosis. CONCLUSIONS: This ES is user-friendly, easy
      to update and can answer clinical problems the ophthalmologist has to cope with
      in diagnosis and therapy of intraocular pressure disorders.

PMID- 8745764
TI  - [Visual and sensory results of surgical treatment of cataract in children.
      Apropos of 135 cases].
AB  - PURPOSE: Visual outcome after cataract surgery in children. METHODS: The authors
      studied the functional results (visual acuity and binocular vision) of 135
      children operated for unilateral or bilateral cataracts during the 9-year period
      1985-1994. Aphakia was corrected by an implant within the capsular bag,
      spectacles or contact lenses. RESULTS: For bilateral cataracts, (68 patients),
      mean visual acuity > 20/40 and normal binocular vision are found together in
      cases of late appearance operated after 7 months of age. Pseudophakic eyes
      regained visual acuity greater than 20/40 more often than non-implanted eye, with
      a statistically significant difference (P < 0.001). Binocular vision was also
      obtained more often in children after implantation (P < 0.05). The functional
      results of operations on early cataracts treated before the age of 8 months were
      not as good because of abnormal development of the foveolar function. For
      unilateral cataracts (67 patients), the prognosis was poor when operated before
      the age of 8 months. Visual acuity rarely exceeded 20/200 however the aphakia was
      corrected. Prognosis was better for partial cataracts and late-appearing
      cataracts. Implantation appeared to be of more benefit, with a statistically
      significant difference (P < 0.05) for visual acuity greater than 20/40 in
      children receiving an implant. CONCLUSION: Regained binocular vision and absence
      of amblyopia depend on the quality of previous visual experience and absence of
      post-operative strabismus. Implantation appears beneficial for final visual
      results.

PMID- 8745765
TI  - [Intercapsular implantation in the management of cataract in children. Study of
      87 cases and comparison to 88 cases without implantation].
AB  - PURPOSE: We compared the surgical results and complications between two groups of
      children operated for cataract with or without lens implantation. METHOD: One
      hundred seventy-five eyes in 126 children, aged 15 days to 16 years were operated
      for cataract with a surgical procedure of limbus phacoaspiration. Eighty-seven
      received a primary intercapsular one-piece PMMA Intra Ocular Lens (IOL).
      Conditions for lens implantation were restrictive: strictly intercapsular, no
      other ocular pathology, at any age in unilateral and usually after 3 years of age
      in bilateral cataracts. Follow up ranged from 6 months to 10 years. RESULTS:
      Primary fibrinous anterior chamber reaction was seen in all patients in the IOL
      group. It always regressed under medical treatment. Glaucoma, retinal detachment
      and reoperations rates were similar in the two groups. There is a high
      correlation (p < 0.001) between initial anterior vitrectomy and keeping a clear
      visual axis, even in the eldest group, but no difference with or without IOL.
      Local tolerance of IOL was evaluated. No effect on visual results was evidenced.
      Evolution of refraction in pseudophakic eyes doesn't show evident myopic shift.
      Secondary myopias found in older groups might be associated to "genetic" myopia
      more than a consequence of implantation. CONCLUSION: Intercapsular lens
      implantation in children does not statistically increase the rate of complication
      of cataract surgery. It can be chosen if a real functional benefit is expected.
      The choice of IOL's power depends on biometric results which are a function of
      age. Under correction is usually recommended but immediate emetropia must be the
      aim in unilateral cases to ease amblyopia's treatment.

PMID- 8745766
TI  - [Characteristics of corneal topography in candidates for surgery for myopia].
AB  - INTRODUCTION: Videokeratography analyses the corneal anterior topography. It is
      necessary in refractive surgery to estimate the anatomical effect of the surgery
      and to eliminate early Keratoconus. METHODOLOGY: Corneal anterior topography was
      studied on 70 consecutive patients (140 eyes) candidates for low myopia surgery (
      1 to -6); 87 eyes were wearing regularly contact lenses. With the topographic
      analysis machine of EYESYS compagny, keratometry (Km) at 3 mm, astigmatism (delta
      K) at 3 mm, I-S value at 3 mm and 5 mm according to Rabinowitz method were
      measured in each eye. RESULTS: The average keratometry was 43.50 +/- 1.87 D. The
      average astigmatism was 0.909 +/- 0.75 D. 51 eyes presented an asymmetric corneal
      and among them 32 ware contact lenses regularly; 8 eyes out of 140 (6%) presented
      the association of an high central Keratometry value (> or = 47 D) and corneal
      asymmetry (I-S > 0.5 value). COMMENTS: The incidence of Keratoconus is higher in
      a candidate population for refractive surgery by self-selection. Its frequency is
      difficult to evaluate accurately because of the present limits for the diagnostic
      measures. In this population, it seems to represent about 6%. CONCLUSION: The
      videokeratography before refractive surgery is necessary to reveal corneal
      anterior topography abnormalities and to eliminate early Keratoconus.

PMID- 8745767
TI  - [Orbital dermoid cysts. Apropos of a case].
AB  - We report the case of a 53 year-old female patient with an orbital dermoid cyst.
      A mass effect with proptosis, hypotropia and choroidal folds was noted. Imaging
      aspects (radiography, ultrasonography and computed tomography) were highly
      suggestive of a deep orbital dermoid cyst. A fronto-temporal neuro-surgical
      approach allowed complete removal of the tumour. Histopathology confirmed the
      diagnosis of dermoid cyst. The incidence of orbital dermoid cyst falls
      significantly after the second decade of life thus making our clinical case
      original.

PMID- 8745768
TI  - [Williams-Beuren syndrome: diagnosis and ocular manifestations].
AB  - A 24-year-old woman presented with a Williams-Beuren Syndrome which included a
      characteristic facies, cardiovascular dysfunction and neurologic troubles.
      Ophthalmic examination showed a stellate pattern of the iris and tortuosities of
      the retinal vessels. Knowledge of these ocular manifestations could help early
      diagnosis.

PMID- 8745769
TI  - [Spontaneous corneal perforation and conjunctival molluscum contagiosum in a AIDS
      patient].
AB  - A case of spontaneous corneal perforation occurred in a 32 year-old patient with
      AIDS who presented eyelid and conjunctival molluscum contagiosum. The mechanism
      of this perforation was discussed in light of data found in the literature. The
      rarety, severity and difficulty in diagnosing molluscum contagiosum are
      emphasized.

PMID- 8745770
TI  - [Current medical treatment of dry eye].

PMID- 8745771
TI  - [Treatment of cystoid macular edema occurring 2 years after cataract surgery].

PMID- 8745772
TI  - A century of ENT radiology.

PMID- 8745773
TI  - Pre-operative information in mastoidectomy: what about the facial nerve and
      hearing loss?
AB  - Facial nerve palsy and hearing impairment are accepted risks of mastoid surgery.
      However, at present there are no guidelines as to whether a patient must be
      informed of the potential risk to the facial nerve and hearing during mastoid
      surgery. Currently the law states that the surgeon should do what a 'reasonable
      doctor' would do under similar circumstances but exactly what this entails is not
      clear. A recent publication established that 16 per cent of British surgeons did
      not tell their patients about the risk to the facial nerve and 13 per cent about
      the risk of hearing loss. A survey of South African surgeons showed a different
      picture with only 57 per cent of surgeons informing their patients of possible
      facial nerve injury and 71 per cent about hearing loss. One of the reasons stated
      was that this information might deter the patient from having a necessary
      operation. This raises the question of excessive information disclosure and its
      possible legal consequences if excessive information leads a patient into making
      an unbalanced judgment owing to his/her lack of medical training, prejudices or
      personality. In this survey 25 per cent of South African surgeons have had
      patients refuse surgery after being informed of the risk to facial nerve and
      hearing. The decision whether to inform the patient about these risks should be
      individualized for every patient after the surgeon has audited his/her results
      and assessed the patients prejudices, personality and level of education.

PMID- 8745774
TI  - Acute labyrinthitis associated with systemic Candida albicans infection in ageing
      mice.
AB  - The yeast Candida albicans is an important opportunistic pathogen that has been
      associated with disease of the inner ear. This study describes the histopathology
      of acute labyrinthitis caused by systemic infection with C. albicans in aging
      inbred mice. Within four days after infection, yeast and hyphal forms of
      C.albicans were found in the membranous labyrinth. The utricle and the adjacent
      parts of the ampullary regions of the semicircular canals were most severely
      affected, but damage was also seen in the scala media, the scala tympani, the
      saccule, and the scala vestibuli. In the utricle, the lining epithelium of the
      membranous labyrinth was disrupted, and the lining cells of the vestibular
      membrane showed foci in which the membrane was disrupted. The data suggest that
      age may represent a risk factor for fungal labyrinthitis.

PMID- 8745775
TI  - The paranasal sinuses before and after radiotherapy for nasopharyngeal carcinoma:
      a computed tomographic study.
AB  - A study comparing the pre- and post-radiotherapy computed tomographic scans of
      patients treated for nasopharyngeal carcinoma revealed that the incidence of
      major mucosal abnormality was significantly increased and approximately doubled
      after radiotherapy. The most significant factor predicting major mucosal
      abnormality after radiotherapy was the presence of tumour in the sinus before
      treatment. In the maxillary sinus there was significant association of major
      mucosal abnormality before and after radiotherapy although this was not so for
      the other sinuses. The mucosal changes observed were evident as early as six
      months after radiotherapy.

PMID- 8745776
TI  - Abnormalities of the paranasal sinuses in patients with nasopharyngeal carcinoma:
      a computed tomographic study.
AB  - A retrospective study of computed tomography scans of the paranasal sinuses of
      131 control subjects in Hong Kong revealed minor mucosal abnormalities in more
      than half of the ethmoid sinuses. Major abnormalities were present in seven per
      cent of maxillary, five per cent of anterior ethmoid and four per cent of
      posterior ethmoid sinus. In 85 patients with nasopharyngeal carcinoma the
      prevalence of minor mucosal abnormalities in the sinuses was similar to that of
      the control group but major mucosal abnormalities were significantly more common
      in the anterior and posterior ethmoids at 15 per cent and 21 per cent of the
      respective sinuses (p < 0.001).

PMID- 8745777
TI  - Endoscopic ligation of the sphenopalatine artery (ELSA): a preliminary
      description.
AB  - Two cases of transantral endoscopic ligation of the sphenopalatine artery are
      presented, and the surgical technique described. The main advantage of this
      minimal access operation being avoidance of the morbidity associated with the
      conventional Caldwell-Luc approach.

PMID- 8745778
TI  - Monitoring of intra-operative visual evoked potentials during functional
      endoscopic sinus surgery (FESS) under general anaesthesia.
AB  - Functional endoscopic sinus surgery (FESS) is an effective treatment for
      inflammatory sinus disease. The potential for major complications during FESS is
      high particularly under general anaesthesia. The most serious of these is injury
      to the eye leading to blindness. We looked at the feasibility of monitoring flash
      visual evoked potentials (VEP) simultaneously from both eyes during FESS. Five
      patients were included in this preliminary study. A haptic contact lens connected
      by fibreoptic cable to a photostimulator was placed on the eyes and stimulus of
      comparable intensity to a conventional strobe was delivered. We found that an
      increase in P100 latency to be an indicator of optic nerve compression. However,
      for this to be useful the diastolic blood pressure should not fall below 50 mmHg,
      the oxygen saturation should be maintained at 98 per cent and bleeding should be
      minimized during surgery. The changes in the amplitude of P100 was not found to
      be useful. While there is no substitute for learning endoscopic surgery by
      cadaveric dissection and supervised training we believe that in selected cases
      VEP monitoring can be employed with profit.

PMID- 8745779
TI  - Survival times of Provox valves.
AB  - This study was performed to assess the survival times of the Provox valve in the
      Manchester area. Thirty-nine patients from four hospitals, representing 81 valve
      failures, were studied. The effects of the timing of the tracheo-oesophageal
      puncture, previous radiotherapy, and the presence and timing of cricopharyngeal
      myotomy on valve life were analysed. Regression analysis using an extension of
      the Cox model to allow strata showed that the lifetime of the first valve only is
      adversely affected by previous radiotherapy. The other covariates do not have a
      statistically significant effect on valve survival. The median valve survival is
      4.5 months, (range one to 12 months). A small percentage of valve users with
      particularly frequent valve failures may require additional support and prolonged
      anti-fungal therapy.

PMID- 8745780
TI  - Ultrasound versus physical examination in staging carcinoma of the mobile tongue.
AB  - Surgical therapy for early lesions of the tongue should have the potential to be
      both oncologically sound and easy to rehabilitate. Obviously, the amount of
      tongue left behind after surgery is proportional to the post-operative function.
      Hence accurate mapping of the diseased tongue is of paramount importance in order
      to limit or extend the resection margins. We have evaluated the use of ultrasound
      in carcinoma of the tongue, and also compared its relative accuracy with physical
      examination for determining the extent of growth, keeping the histopathological
      size as a gold standard. We found that ultrasound is more accurate in detecting
      T2 and T3 tumours than T1 lesions. Intraoral sonographic mapping may be the
      answer for such small lesions. In addition, ultrasonography is beneficial in
      showing spread to contiguous areas of the tongue. However, post-radiation
      fibrosis and frank residual disease were not differentiated accurately by
      ultrasound. Thus ultrasonography can be an effective investigative tool and
      together with physical examination it can increase diagnostic accuracy leading to
      precise surgery for carcinoma of the tongue.

PMID- 8745781
TI  - Cervical lymphadenopathy secondary to atypical mycobacteria in children.
AB  - Non-tuberculous mycobacterial (NTM) infections usually present as an enlarged
      lymph node in the neck of a non-immunocompromised child. The differential
      diagnosis includes bacterial adenitis, malignant disease and tuberculosis. The
      definitive diagnosis relies upon isolating the organisms in culture. The
      treatment is complete surgical excision with, or without, anti-tuberculous
      chemotherapy. Ten cases of NTM infections are presented with a discussion of the
      aetiology and treatment of this condition.

PMID- 8745782
TI  - Pleomorphic adenoma of the external auditory canal: a case report and review of
      the literature.
AB  - Pleomorphic adenoma arising in the external auditory canal is rare. We report the
      case of a 38-year-old man. To better grasp the clinical features and natural
      history of this uncommon tumour, we also reviewed the worldwide literature and
      found 24 similar cases, which we analysed together with our own.

PMID- 8745783
TI  - Relief of severe hyperacusis and diplacusis in a deafened ear by cochlear
      labyrinthectomy.
AB  - A professional musician with intolerable hyperacusis and dysharmonic diplacusis
      in a severely deafened ear was successfully relieved of his symptoms by
      deliberate destruction of the cochlea.

PMID- 8745784
TI  - Sudden deafness as the sole presenting symptom of diabetes mellitus--a case
      report.
AB  - This paper reports an undiagnosed diabetic presenting to an otolaryngologist with
      sudden deafness of six days duration as the only symptom. Appropriate
      investigative and treatment measures resulted in recovery of hearing.

PMID- 8745785
TI  - Should nasopharyngeal biopsy be mandatory in adult unilateral glue ear?
AB  - Unilateral secretory otitis media is a recognized presenting feature of
      nasopharyngeal neoplasia. In the two cases presented, biopsy from the nasopharynx
      revealed an unsuspected underlying adenocarcinoma. The need to biopsy the normal
      looking post-nasal space is highlighted.

PMID- 8745786
TI  - Leiomyoma of the nasal septum: report of a case and review of the literature.
AB  - Leiomyomas of the nasal cavity are very rare. A case of leiomyoma arising in the
      nasal septum is presented. The tumour was removed by endoscopic sinus surgery.
      The literature on the topic is reviewed.

PMID- 8745787
TI  - Cavernous sinus thrombosis following manipulation of fractured nasal bones.
AB  - Septic cavernous sinus thrombosis is a serious infective condition with a high
      mortality and morbidity. We report the first case to our knowledge of septic
      cavernous sinus thrombosis following manipulation of fractured nasal bone under
      general anaesthesia. The patient later developed complications of pneumonia with
      pleural effusion, a vegetative lesion of the mitral valve, and blindness.

PMID- 8745788
TI  - Laryngotracheal separation under local anaesthesia for intractable salivary
      aspiration: cricoidectomy with fibrin glue support.
AB  - Chronic salivary aspiration can cause life-threatening pneumonia in a patient
      whose laryngeal function is completely lost. We report a patient who had
      laryngotracheal separation with cricoidectomy under local anaesthesia. The
      simplicity and reliability of the procedure were improved by using fibrin glue
      and the outcome was most satisfactory.

PMID- 8745789
TI  - Recurrent laryngeal papillomatosis developing into laryngeal carcinoma with human
      papilloma virus (HPV) type 18: a case report.
AB  - We report a case of recurrent laryngeal papillomatosis which developed into
      laryngeal squamous cell carcinoma 11 years after the first diagnosis.
      Interestingly, we could identify HPV type 18 DNA in the carcinoma tissue using
      the polymerase chain reaction (PCR). Other known risk factors of irradiation,
      smoking, exposure to chemical agents, or a hereditary tendency to malignant
      tumours were not present in this case. Our finding suggests that HPV type 18 is
      another aetiological agent for laryngeal carcinoma.

PMID- 8745790
TI  - Staphylococcus aureus peritonsillar abscess in an 11-week old infant.
AB  - A case of Staphylococcus aureus peritonsillar abscess in an 11-week-old infant is
      described. The importance of peritonsillar abscess culture and its changing
      management is discussed.

PMID- 8745791
TI  - Cervical necrotizing fasciitis: a distinct clinicopathological entity?
AB  - Necrotizing fasciitis of the head and neck has previously been classified as a
      homogeneous group. We present two cases of necrotizing fasciitis confined to the
      neck and demonstrate with a review of the literature that cervical necrotizing
      fasciitis and craniofacial necrotizing fasciitis are two distinct
      clinicopathological conditions.

PMID- 8745792
TI  - Retro- and para-pharyngeal ganglioneuroma.
AB  - A patient with slight dysphagia and dyspnoea on exertion was referred to us. We
      diagnosed a large retro- and para-pharyngeal ganglioneuroma. The mass was
      surgically removed in toto. The case is presented and the features are discussed.

PMID- 8745793
TI  - Acute suppurative parotitis and facial paralysis.
AB  - A case of facial nerve paralysis secondary to acute suppurative parotitis is
      described. This is a rare complication in the absence of malignant processes in
      the parotid.

PMID- 8745794
TI  - Lipoma of the parotid gland presenting with facial palsy.
AB  - Facial palsy in the presence of ipsilateral parotid tumour is considered to be
      pathognomonic of malignancy. However, benign neoplasms and inflammatory lesions
      of the parotid gland have been reported to present with facial palsy. A case of
      lipoma of the parotid gland associated with partial facial paralysis is reported.
      Lipomas are very rarely seen in this site. To our knowledge, a lipoma of the
      parotid producing facial paralysis has not been described previously. This report
      highlights the difficulties in pre-operative diagnosis and management of such a
      lesion.

PMID- 8745795
TI  - Tuberculous parotitis: limiting the role of surgery.
AB  - The diagnosis of parotid gland involvement with tuberculosis has traditionally
      been made after superficial parotidectomy. We present four cases that suggest
      that fine needle aspiration cytology followed by antituberculous therapy can
      avoid the need for surgery in this uncommon condition.

PMID- 8745796
TI  - Cellular benign fibrous histiocytoma of the external auditory meatus.
AB  - A rare case of cellular benign fibrous histiocytoma (BFH) of the external
      auditory canal is presented with a discussion of its pathology and management.

PMID- 8745797
TI  - Hairy polyp of the tonsil.
AB  - Hairy polyps or dermoids of the oro- and naso-pharynx are benign lesions
      containing elements of both ectodermal and mesodermal origin. We report a case of
      a hairy polyp arising from the tonsil in a three-week-old infant. This presented
      as an intermittent swelling in the mouth, which was successfully removed under
      general anaesthesia. To our knowledge this is only the third case of a hairy
      polyp arising at this site to be reported. We discuss the terminology applied to
      these lesions and review the literature.

PMID- 8745798
TI  - Raised ABR threshold after suction aspiration of glue from the middle ear: three
      case studies.

PMID- 8745799
TI  - Middle ear pressures in patients with nasopharyngeal carcinoma and their clinical
      significance.

PMID- 8745800
TI  - Outcomes measurement in orthopaedic trauma surgery.

PMID- 8745801
TI  - The application of the limited contact dynamic compression plate in the upper
      extremity: an analysis of 114 consecutive cases.
AB  - We sought to assess the clinical effectiveness of a new plate design which offers
      improved biological and biomechanical features, the limited contact dynamic
      compression (LCDC) plate. We analysed 114 LCDC plates applied consecutively for
      upper extremity fractures or reconstruction in 94 patients. Three patients were
      lost to follow-up, leaving 111 plates in 91 patients followed to definitive
      fracture/osteotomy outcome. Thirty-seven plates were applied for reconstruction
      in 35 patients, including 11 where standard implants had failed. Fifty-six
      patients had 74 plates applied for acute fractures including 12 open fractures,
      23 multiply injured patients, 26 patients with concomitant fractures and seven
      associated neurovascular injuries. All patients were followed to definitive
      outcome. Union was achieved at an average of 10.7 weeks in 105 platings, while
      three delayed unions eventually united without further intervention, an overall
      union rate of 108/111, or 97.3 per cent. There were no mechanical failures of the
      plates or screws. In this large series a union rate of 97.3 per cent with no
      implant failures confirms its clinical application for traumatic and
      reconstructive problems in this area. Improved contouring, easier screw
      placement, decreased interference with cortical bone blood flow and excellent
      union rates are definite short-term advantages. Theoretical long-term benefits of
      decreased stress-shielding and lower refracture rates will require longer follow
      up.

PMID- 8745802
TI  - The use of CT scanning by accident and emergency departments in the UK: past,
      present and future.
AB  - To determine the access to and use of computed tomography (CT) scanning by
      Accident and Emergency (A&E) departments a questionnaire was sent to all major
      A&E departments in the UK. Although CT scanners were present in over 80 per cent
      of the 225 responding hospitals, many centres (including 15.8 per cent of those
      with a CT scanner on site) did not have 24 h scanning facilities for emergency
      cases. Few departments (26 per cent) have agreed protocols with their radiology
      departments with regard to CT scanning and some departments transferred cases for
      emergency CT scans at another hospital. There are deficiencies in access to CT
      scanning in a significant number of hospitals. This results in some patients
      undergoing hazardous and in our view unnecessary transfer for scanning. Little
      use is made of agreed protocols between A&E and Radiology departments to simplify
      and speed up the process of arranging CT scans. We feel that the deficiencies
      identified need to be addressed particularly in the assessment of head injury.

PMID- 8745803
TI  - Early mobilization in the treatment of Colles' fracture: a 3 year prospective
      study.
AB  - Ninety consecutive women with unilateral Colles' fractures were randomized into
      two different treatment groups. The control group was treated for 5 weeks in
      conventional short-arm, below the elbow plaster of Paris casts. The other group
      (N = 45) was treated similarly in plaster casts for 3 weeks and then had flexible
      casting applied for the remaining 2 weeks which allowed for early joint
      mobilization. Functional recovery was assessed by measuring grip strength and
      joint mobility at intervals over the 3 years. Radiographic and overall
      assessments were also made during 3 year course of study. Virtually all patients
      reported greater comfort after switching to the flexible casting. Mean grip
      scores and joint mobilities were higher at all time points with early
      mobilization, reaching levels of statistical significance at 6 months for grip
      score and at 3 months for joint mobility. By 3 years most differences between
      treatment groups had resolved. We found no evidence that early mobilization was
      detrimental to recovery. We conclude that early mobilization is a satisfactory
      treatment option for Colles' fracture, and may, in fact, hasten functional
      recovery.

PMID- 8745804
TI  - Percutaneous transcatheter embolization in multiply injured patients with pelvic
      ring disruption associated with severe haemorrhage and coagulopathy.
AB  - Six multiply injured patients with pelvic fractures were treated by percutaneous
      transcatheter embolization during a 10 month period. Diagnosis and therapy were
      carried out early in two cases (first day of admission into the trauma unit).
      Three patients were treated on the second day after admission. The last patient
      was embolized on the third day. Two patients underwent one and two remote
      embolizations. Embolization was indicated due to uncontrolled haemorrhaging,
      requiring large volumes of packed erythrocytes (median: 11.3) and fresh frozen
      plasma units (median: 6.8). Three patients had severe coagulopathy (disseminated
      intravascular coagulation). From two to 12 arteries were embolized per patient
      (median: 5). After successful transcatheter embolization, the circulation and
      coagulation stabilized rapidly without recurrence of haemorrhage or coagulopathy.

PMID- 8745806
TI  - Pulled elbow--not the effect of hypermobility of joints.
AB  - A detailed description of pulled elbow is missing from standard orthopaedic text
      books. Recently it has been reported that the prevalence of hypermobility among
      children with pulled elbow is higher than that in the normal population and that
      pulled elbow can be considered to be a consequence of joint hypermobility. Two
      hundred children with pulled elbow comprising 106 girls and 94 boys (age range 3
      84 months, mean age 24 months) were treated and evaluated for signs of
      hypermobility in a prospective study. Hypermobility of joints was noted in 17
      (8.5 per cent) of children who had a pulled elbow while in the 71 children in
      whom there had been more than one episode, the rate of hypermobility was 8.4 per
      cent. Comparison of these results with a control group of 100 normal children, in
      whom 10 (10 per cent) exhibited hypermobility, showed no association between
      joint hypermobility and an increased incidence of pulled elbow. The anatomical
      construction of the radial head, relative plasticity of the cartilage and the
      immature annular ligament in young children possibly predisposes them to pulled
      elbow, the incidence of which is increasing in our modern physically competitive
      society where children are participating in a wide range of physically demanding
      sports activities. Pulled elbows can also occur in children with hypermobility of
      joints, but there is no evidence that the incidence has increased.

PMID- 8745805
TI  - An experimental model for non-union in rats.
AB  - Few studies of the biological changes which occur in impaired fracture repair and
      non-union have been carried out, and creating an appropriate model for advanced
      biochemical studies of non-union has proved to be a demanding task. This paper
      presents a standardized experimental model for producing non-union in rat femurs,
      for use in biochemical studies of non-union. A mid-diaphyseal fracture with a
      rotationally unstable fixation was performed in rats with a mean weight of over
      330 g and mean age of over 10 weeks. Radiologically and histologically (Alcian
      blue and Safranin O stainings) the signs of undisturbed fracture healing were
      observed until 3 weeks after the fracture. Thereafter there was evidence that
      chondrocytic activity ceased, with no signs of formation of calcifying bridging
      callus. From the seventh week onwards, all elements necessary for a calcifying
      callus were lost; and the histological picture tended to be of scar tissue bond
      between the fracture ends.

PMID- 8745807
TI  - Forearm fractures in children: avoiding redisplacement.
AB  - We reviewed eighty-six children with closed extra-articular distal forearm
      fractures to determine the factors responsible for early redisplacement. The most
      important favourable prognostic factor was a perfect anatomical reduction on the
      immediate post-reduction radiograph. This was far more likely when the
      manipulation was performed by an experienced surgeon.

PMID- 8745808
TI  - Lymphocoele of the thigh following blunt war injury.

PMID- 8745809
TI  - Traumatic separation of the upper femoral epiphysis in a 15-month-old girl: an
      unusual mechanism of injury.

PMID- 8745810
TI  - Complete avulsion of a tendon of flexor digitorum profundus from its myotendinous
      junction.

PMID- 8745811
TI  - Vascular injury following closed proximal tibial fracture: beware the extension
      injury.

PMID- 8745812
TI  - Displaced fractures of the proximal humerus: a case report which highlights the
      difference in outcome using two orthodox methods of treatment.

PMID- 8745813
TI  - Post-traumatic intrasplenic pseudoaneurysm successfully managed by embolization.

PMID- 8745814
TI  - The management of fractures from missiles.

PMID- 8745815
TI  - External fixation as a primary and definitive treatment of open limb fractures.

PMID- 8745816
TI  - Femoral neck fracture: a complication of femoral nailing.

PMID- 8745817
TI  - The pelvic fracture in childhood: a report supporting nonoperative management.

PMID- 8745818
TI  - Acute traumatic patellar dislocation: the importance of skyline views.

PMID- 8745819
TI  - [Experimentation and clinical trials in pediatric nutrition. Legal obligations
      and rules of management. French Society of Pediatrics. Committee on Nutrition].

PMID- 8745820
TI  - [Increasing frequency and diagnostic difficulties in intestinal stenosis after
      necrotizing enterocolitis].
AB  - BACKGROUND: Stenosis after necrotizing enterocolitis (NEC) has increased from 15
      to 57% over the last 10 years in our unit. The aim of this study is to point out
      the difficulty of diagnosis and treatment, and search for factors explaining this
      increase. PATIENTS AND METHODS: From 1986 to 1991, 42 newborns had NEC, followed
      by intestinal strictures in 19 of them (57% of the 33 survivors). Data from these
      19 patients were compared with those of the 14 without intestinal strictures. The
      33 survivors were also compared with those of an earlier study including 25 NEC
      seen from 1979 to 1986. RESULTS: After medical treatment (n = 12), intestinal
      stenosis led to occlusion after three weeks, was located to both small and large
      intestine and was short and tight. After surgical treatment (n = 7), stenosis was
      shown by opacification before digestive anastomosis (n = 5) or revealed by
      occlusion (n = 2); it stayed on the colon, was long or multiple, requiring
      extensive resections. No difference could be found between data from patients
      with or without stenosis. Although newborns were actually more premature, the
      risk of stenosis was more frequent when newborns of same gestational ages and/or
      weights were compared. CONCLUSIONS: Intestinal stenosis is a frequent
      complication after NEC; its diagnosis is often difficult and requires extensive
      digestive resections. No clinical or therapeutic factor could be found to explain
      the actual increase in frequency.

PMID- 8745821
TI  - [Mental prognosis in scaphocephaly].
AB  - BACKGROUND: The mental prognosis of scaphocephaly remains a controversial issue,
      and surgery is performed for functional or aesthetical reasons without clear
      evidence in the literature of which is the most important. PATIENTS AND METHODS:
      Three hundred and ninety six children with scaphocephaly were prospectively
      studied to analyse the correlation between age, intracranial pressure (ICP) and
      mental outcome. Before any treatment, the intracranial pressure was recorded
      (systematically during the first period of the study); the mental level was
      evaluated at first consultation and after a mean five-year follow-up. The mental
      evolution was compared whether the child was operated or not. RESULTS: The mental
      outcome of the patients was good in most of the cases whether or not they had
      been operated. There were significantly more normal patients in the
      scaphocephalies seen before one year of age at first consultation (P < 0.001)
      than in those seen after one year of age. There were significantly more
      abnormally high intracranial pressure cases in the group of patients who were
      seen later than one year of age (P = 0.0015). There were more retarded patients
      in the group with increased ICP, but the difference was not significant (P =
      0.17). There was no correlations between ICP and final IQ neither in operated nor
      in non-operated patients. Conversely, a correlation was found between the early
      and late psychometric assessments in all patients. CONCLUSIONS: The main
      predictive factor of mental outcome appears to be the initial developmental
      level. Since the mental level was worse in the older children, and since the
      surgery does not influence the functional outcome when the initial mental level
      is low, we can conclude that the indication to perform surgery in scaphocephaly
      is sometimes not only a cosmetic problem.

PMID- 8745822
TI  - [Pain in lumbar puncture. Results of a 2-year discussion at the French Society of
      Pediatric Oncology].
AB  - BACKGROUND: Lumbar puncture is a common procedure in pediatric onco-hematology.
      Repeated invasive painful procedures may contribute to increase distress
      displayed during medical treatment, and cause regression, depression and other
      psychological disorders. MATERIAL AND METHODS: A two-year workshop of the Societe
      francaise d'oncologie pediatrique was reviewed through a questionnaire assessing
      changes in technical management of lumbar puncture, local anesthesia, sedation
      and cognitive-behavioral interventions. RESULTS: Significant changes were found
      for pain assessment, local anesthesia procedures, and nitrous oxide
      administration. The extensive use of the Emla cream largely contributed to reduce
      pain. Anxiety however remained an unsolved problem, particularly among young
      children. CONCLUSION: Pain in pediatrics remains a major challenge. This workshop
      is a model of reflexion to achieve a better management of pain during invasive
      medical procedures.

PMID- 8745823
TI  - [Analysis of pediatric home care services of the Assistance Publique--Hopitaux de
      Paris].
AB  - BACKGROUND: The Home Health Care services for children in Paris was recently
      established and it is interesting to analyse the first results of their
      activities. POPULATION AND METHODS: A random sample (n = 157) of the 418 children
      admitted to home health care in the Assistance publique-Hopitaux de Paris (HAD-P)
      in 1991 has been studied; only one episode of care was analyzed for each child.
      The data analysed included sociodemographic characteristics of the children,
      their clinical diagnosis and the care received. RESULTS: More than half of the
      children presented chronic diseases. Follow-up of newborn children was the main
      reason for admitting children with acute conditions. Housing and socioeconomic
      conditions were poor for a significant number of children. A seasonal pattern was
      found, with higher activity in the beginning and in the end of the year.
      CONCLUSIONS: More efforts are needed to develop complementarity between hospital
      based and home health care services, beginning with improved communication of
      detailed information regarding home health care objectives and conditions.

PMID- 8745824
TI  - [Severe parvovirus B19 infection in an immunocompetent child with hemophilia A].
AB  - BACKGROUND: B19 parvovirus is a widespread virus whose typical manifestations in
      immunocompetent children are erythema infectiosum, acute erythroblastopenia and
      fetal anemia. CASE REPORT: An 11 year-old immunocompetent patient with hemophilia
      A was referred for an hemorrhagic syndrome. Forty days after a pasteurized
      coagulation factor concentrates treatment, and after 12 days of treatment with
      solvent/detergent factor VIII concentrates, he developed fever, consciousness
      disorders, pancytopenia, liver cytolysis and probably minor haemophagocytic
      syndrome, associated with human parvovirus B19 infection. His clinical state
      returned to normal within 15 days. A retrospective study revealed that the
      patient had received every day for 12 days, one parvovirus B19 polymerase chain
      reaction positive batch before the occurrence of symptoms. CONCLUSION: This case
      highlights the possibility of severe parvovirus B19 infection transmitted by
      clotting factors prepared from large pools of plasma. The use of recombinant
      factors would allow to reduce human virus contamination, even if immune risk has
      to be more accurately assessed.

PMID- 8745825
TI  - [Myelofibrosis regressing under corticotherapy and intravenous immunoglobulins in
      an infant].
AB  - BACKGROUND: Primary myelofibrosis is rare in infants and children; its
      association with auto-immune markers has only been reported in adults. CASE
      REPORT: An 8 month-old girl was admitted because of severe anemia and
      neutropenia. The marrow aspirate showed dysgranulopoiesis and partial
      interruption of maturation after the myelocyte level. The bone marrow biopsy
      revealed reticulinic myelofibrosis. The condition worsened with development of
      agranulocytosis and thrombocytopenia. Investigations ruled out malignant
      hemopathy, metastatic infiltration of the marrow and osteopathy. A
      myelodysplastic syndrome was discussed, but presence of anti-granulocyte auto
      antibodies and positive Coombs test led to consider an autoimmune etiology. A
      corticosteroid therapy was attempted, effective only on the platelet lineage.
      Addition of intravenous gammaglobulin therapy corrected the problem. After a 24
      month-course of the disease, it was necessary to prolong therapy. CONCLUSION: The
      efficacy of gammaglobulins may be an additional argument for auto-immunity,
      although no other auto-immune pattern has been observed in our patient, contrary
      to reported cases in adults.

PMID- 8745826
TI  - [Lethargic form of acute intestinal intussusception in an infant].
AB  - BACKGROUND: Intussusception encephalopathy, a misleading form in which
      neurological symptoms are obvious, is classic but rarely described. CASE REPORT:
      A 21 month-old infant was admitted because he had suffered from fluctuating
      consciousness and apathy for a few hours. Vomiting occurred soon afterwards.
      Search for dehydration, meningitis, encephalitis, poisoning... was negative; the
      abdomen was tender leading to ultrasonography that showed a sausage-shaped tumor.
      The ileocolic intussusception was successfully reduced with a gas enema.
      CONCLUSION: A striking degree of lethargy associated with vomiting may overshadow
      to a considerable extent the classical intestinal manifestations. A possible
      endogenous opioid poisoning by massive secretion of endorphins during pain's
      paroxysm is one of the hypotheses explaining this type of presentation.

PMID- 8745827
TI  - [Acute left-side appendicitis: diagnostic contribution of tomodensitometry].
AB  - BACKGROUND: Some cases of left-sided appendicitis related to malrotation or situs
      inversus have been reported. Another type of left-sided appendicitis is reported.
      CASE REPORT: A 9 year-old boy was admitted suffering from a 2-day history of
      severe left-sided abdominal pain of the lower quadrant with fever at 38 degrees
      C. He presented abdominal tenderness and guarding, maximal in the left lower
      quadrant. His leukocyte count was 22,000/mm3. Ultrasonography showed a digestive
      tubular structure with thick walls in the left lower quadrant. CT scan revealed a
      dilated right-sided appendix with localized perforation, whose extremity was
      located in the left lower quadrant along the lateral wall. The diagnosis was
      confirmed by median laparotomy. CONCLUSION: Left-sided appendicitis can also be
      related to a dilated right appendix with its extremity in the left lower-quadrant
      near the lateral wall. CT scan can then be helpful for diagnosis when
      ultrasonography remains unconclusive.

PMID- 8745828
TI  - [Eating disorders and suicide attempts in 2 dance students].
AB  - BACKGROUND: Young ballet dancers constitute a risk group for anorexia and bulimia
      but suicide attempts have not been reported in this group. CASE REPORTS: Two
      girls, aged 16 and 15 years, respectively, were admitted for suicide attempts.
      Both were students in a ballet school and have been previously treated for
      anorexia nervosa. One of them was depressed and the other had hysterical
      manifestations. CONCLUSION: Psychological monitoring should be systematic in
      young athletic subjects of high-level performances.

PMID- 8745829
TI  - [Bird headed dwarfism in Seckel syndrome. Nosologic difficulties].
AB  - Seckel syndrome is a clinical picture which associates four main features:
      intrauterine growth retardation, microcephaly often due to craniosynostosis,
      orofacial dysmorphology with bird headed appearance and variable mental
      retardation which is present after several months. Malformations of the central
      nervous system, limbs, and hair, may also be observed. On the basis of 78 cases
      reported in the literature, the authors discuss the validity of the morphological
      features of the syndrome. It is likely that the variability in the expressivity
      of each symptom explains its heterogeneity. According to the radiological
      abnormalities, three different forms of the syndrome have been described. Seckel
      syndrome is a genetic disorder with autosomal recessive inheritance. Its
      ethiopatogeny remains unclear. Hopefully linkage studies will allow to map the
      gene in order to determine the underlying abnormal protein.

PMID- 8745830
TI  - [Langerhans cell histiocytosis].
AB  - Histiocytosis X, or Langerhans cell histiocytosis (LCH), is a rare disease, with
      an estimated incidence of 1/200,000 per year in children under 15 years of age.
      It has a wide clinical spectrum, from single bone involvement (eosinophilic
      granuloma) to multisystemic disease with organ failure. The treatment of LCH is
      still controversial. While single system disease may spontaneously recover or
      requires minimal treatment, some multisystemic disease with organ dysfunction may
      resist systemic chemotherapy. The mortality rate in this latter subgroup of
      patients is relatively high and reaches 40% of the cases. A rational approach to
      the treatment of LCH is based on a better understanding of clinical and
      pathophysiological features. A prospective multicentre trial including scientific
      research should be planned, in order to determine the optimal treatment of LCH
      and to ameliorate the prognosis of the severe unresponsive form of the disease.

PMID- 8745831
TI  - [Cerebral palsy and perinatal asphyxia in full term newborn infants].
AB  - Actual data on the frequency of cerebral palsy (CP) and "infirmite motrice
      cerebrale" (IMC), and their relationship with perinatal asphyxia and perinatal
      managements, are presented. In France, the frequency of IMC at 9 years of age,
      approximates 1 per thousand, for the 1972, 1976, 1981 generations. Three surveys,
      two English and one Australian, show an association between perinatal asphyxia
      and CP. However computation of percent attributable risk indicates that asphyxia
      can explain only one case of CP out of six among term neonates. These surveys
      show also that 10% of CP only could be prevented by improving perinatal
      managements. This, in addition to other factors such as the increase in survival
      of very preterm babies, explains the absence of a significant reduction of CP
      frequency despite improvements in the perinatal care.

PMID- 8745832
TI  - [Motor deficiencies in children: for a nosologic clarification in epidemiological
      studies].
AB  - In order to clarify the epidemiological research on childhood motor deficiency in
      France there is a need to better differenciate the two terms used to define this
      pathology: the French term "infirmite motrice cerebrale" (IMC) and the English
      term "cerebral palsy" (CP). The distinction between IMC and CP is highlighted on
      the basis of clinical examples. IMC recovers motor deficiencies which are quite
      similar, however, it can be very difficult to control the variations in its use.
      CP has the advantage of a greater exhaustivity as well as a greater
      reproductibility for epidemiological records. Recently a study was conducted for
      measuring the prevalence of childhood deficiencies in France, and the results
      were expressed either as IMC or as CP. When using the CP definition the
      prevalence rate in France was found to be close to that of foreign studies (1.9
      per thousand). In studies with etiological purposes involving several countries,
      a preliminary agreement on the definition of the clinical groups is absolutely
      necessary.

PMID- 8745833
TI  - [Treatment of urinary tract infection in children].
AB  - The management of urinary tract infection in children must take into account
      several factors, namely the type of bacteria, the localization of the infection,
      the presence of an uropathy and the age of the patient. In acute pyelonephritis,
      the risk of renal scarring justifies a first line treatment with two antibiotics
      to be administrated intravenously in newborns and infants. Treatment must be
      maintained for at least 10 days: double antibiotherapy for 4-5 days, followed by
      oral monotherapy according to the antibiogram. Cystitis requires an oral
      monotherapy for 3-7 days. In any case it is important to search for a cause to
      the infection.

PMID- 8745834
TI  - [Radiological case of the month. Leukoencephalopathy caused by methotrexate in a
      child treated for acute lymphoblastic leukemia].

PMID- 8745835
TI  - [Electric fences for cattle: danger for children?].

PMID- 8745836
TI  - [Prophylaxis of late hemorrhagic disease in newborn infants with vitamin K1 at
      birth].

PMID- 8745837
TI  - [Syncope after niaprazine (Nopron)].

PMID- 8745838
TI  - [Recurrent abdominal pain revealing dermatomyositis].

PMID- 8745839
TI  - [In young children with severe asthma, suspect allergy to peanuts].

PMID- 8745840
TI  - [Left superior vena cava draining in the coronary sinus. The role of fetal
      Doppler cardiography].

PMID- 8745841
TI  - [Hypertrophic gastritis and cytomegalovirus infection].

PMID- 8745842
TI  - Structured management in primary care of patients with epilepsy.

PMID- 8745843
TI  - GP 2000: a general practitioner for the new millennium.

PMID- 8745844
TI  - Women with bleeding in the first 20 weeks of pregnancy: value of general practice
      ultrasound in detecting fetal heart movement.
AB  - BACKGROUND: Real-time ultrasound scanning has made it possible to ascertain
      whether the fetus is alive in women who have bleeding in early pregnancy.
      Portable ultrasound machines are capable of detecting fetal heart movement
      reliably after the ninth week of pregnancy, and can be used in a general practice
      setting. An ultrasound clinic was set up in a health centre and 22 general
      practitioners in the local area could refer women patients with bleeding in early
      pregnancy. AIM: A study was carried out among women with bleeding in early
      pregnancy to compare the presence of fetal heart movement detected at the initial
      ultrasound scan with subsequent fetal survival during the first 20 weeks of
      pregnancy. METHOD: Data were collected during a three-year period on women
      referred opportunistically by their general practitioners. An abdominal scan was
      performed on the same day or the day after presentation and the presence or
      absence of fetal heart movement recorded. Diagnoses and outcome at 20 weeks were
      ascertained from patients' health centre records. RESULTS: A total of 240 women
      with bleeding in early pregnancy were scanned and at the first examination fetal
      heart movement was detected in 115 of the fetuses (48%). Three fetuses were
      subsequently miscarried spontaneously while 109 of the 115 continued to the 20th
      week (95%). Three fetuses had gross abnormalities and these pregnancies were
      subsequently terminated. No heart movement was detected in 117 fetuses (49%); all
      were subsequently miscarried. For eight women scanned it was not clear whether
      fetal heart movement was present. Three of these eight pregnancies survived to
      the 20th week. Predictive values of fetal survival to the 20th week of pregnancy
      from fetal heart movement detected by general practice ultrasound scan for women
      with bleeding in early pregnancy showed a sensitivity of 97% and a specificity of
      98%. CONCLUSION: If fetal heart movement is detected at the initial scan,
      approximately 19 out of every 20 viable pregnancies (those in which the fetus
      appears normal) will not miscarry before the 20th week. Using ultrasound in
      general practice it was possible to identify promptly those women with bleeding
      whose fetus was alive. For those women found to have a non-viable pregnancy,
      appropriate arrangements could be made at an early stage in the knowledge that a
      miscarriage was inevitable, thus avoiding unnecessary bed rest for the patient.
      Where fetal heart movement was detected, there was a good prognosis and thus
      women could be given strong reassurance.

PMID- 8745845
TI  - Epilepsy monitoring and advice recorded: general practitioners' views, current
      practice and patients' preferences.
AB  - BACKGROUND: Epilepsy is a common condition that is managed at the interface
      between primary and secondary care. AIM: A study aimed to describe general
      practitioners' criteria for aspects of optimal epilepsy care and their estimates
      of current levels of care achieved; to compare these estimates with clinical data
      extracted from their patients' medical records; and to compare general
      practitioners' estimates and recorded data with information provided by the
      patients themselves. METHOD: Thirty seven general practitioners from six
      practices in the south Thames region were sent a questionnaire enquiring about
      current practice with regard to general practitioner and specialist monitoring of
      patients with epilepsy and provision of advice, and about their criteria for the
      optimum levels of aspects of epilepsy care. Of patients aged over 15 years in the
      study practices, 0.6% were found to have active epilepsy; 283 of these 326
      patients were sent a questionnaire enquiring about their epilepsy, the service
      and advice provided, and whether they required more information. Responses to the
      general practitioners' questionnaire and to the patients' questionnaire were
      compared and also compared with information extracted from the patients' medical
      records. RESULTS: Ninety five per cent of the general practitioners responded. Of
      255 patient questionnaires (90%) returned, 251 could be analysed. Of 247
      patients, 168 (68%) reported having had no seizure in the previous six months.
      Forty of 241 patients (17%) had a regular arrangement to see their general
      practitioner regarding their epilepsy. Of 191 patients who expressed a
      preference, 116 (61%) reported preferring to receive their epilepsy care mainly
      from their general practitioner. General practitioners reported that ideally
      patients should be monitored in primary care every six months (the median
      recorded frequency was 14 months) and that there should be a record of advice
      given to all patients on driving, adverse effects of antiepileptic drugs, and
      self-help groups. Advice was recorded in patients' records as having been given
      on driving (46% of records), adverse effects of antiepileptic drugs (9%), and
      self-help groups (3%); 82 of 237 patients (35%) reported not receiving enough
      advice. CONCLUSION: Patients generally preferred to receive their epilepsy care
      in general practice. Monitoring and provision of advice were less than optimal
      from both the general practitioners' and the patients' point of view. New
      resources and skills will be necessary to bridge this perceived gap. Specially
      trained nurses may have a role in this monitoring and advice provision.

PMID- 8745846
TI  - Evaluation of the suitability of weekly peak expiratory flow rate measurements in
      monitoring annual decline in lung function among patients with asthma and chronic
      bronchitis.
AB  - BACKGROUND: Early detection and treatment of patients with asthma or chronic
      bronchitis who have a rapid annual decline in lung function is essential in order
      to improve their long-term prognosis. This annual rate of decline can be assessed
      accurately by monitoring the forced expiratory volume in one second (FEV1) which
      is a routine procedure in hospital respiratory laboratories but not in general
      practice. General practitioners usually measure patients' peak expiratory flow
      rate (peak flow) to evaluate lung function. If annual decline in lung function
      can be assessed by monitoring peak flow, this method could be used in general
      practice for detecting patients at an early stage who have a rapid decline. AIM:
      A study aimed to investigate the long-term correlation between FEV1 and peak flow
      among a group of patients in Nijmegen, the Netherlands. METHOD: FEV1 and peak
      flow were monitored in 53 patients with moderate asthma and 78 patients with
      moderate chronic bronchitis over four years. FEV1 was measured in a laboratory
      once every six months and peak flow was measured by patients once a week. The
      correlation between the two sets of measurements was studied for each patient.
      RESULTS: Four-year data for 83 of the 131 patients were analysed; the other 48
      patients received inhaled steroids during the second half of the study period so
      their data were not considered for all the analyses. Of the 83 patients, 35 (42%)
      showed a decrease in both FEV1 and peak flow. Thirty six patients (43%) showed a
      decrease in FEV1 and an increase in peak flow. Four patients (5%) showed an
      increase in FEV1 and a decrease in peak flow and eight patients (10%) showed an
      increase in both rates. Approximately similar results were seen in a separate
      analysis of all 131 patients during the first two years of the study. CONCLUSION:
      No long-term correlation was found between FEV1 and peak flow. Peak flow is not
      capable of detecting annual decline in lung function. Therefore it cannot be used
      to detect patients with asthma or chronic bronchitis who have a rapid annual
      decline in lung function. Spirometers, which measure peak flow and FEV1, could be
      used in general practice. These would allow general practitioners to continue
      measuring peak flow in order to assess short-term changes in lung function while
      providing an important means for monitoring FEV1 to assess long-term changes in
      lung function.

PMID- 8745847
TI  - Setting standards of prescribing performance in primary care: use of a consensus
      group of general practitioners and application of standards to practices in the
      north of England.
AB  - BACKGROUND: There is considerable variation in prescribing, and existing
      standards against which primary care prescribing is routinely judged consist
      largely of local or national averages. There is thus a need for more
      sophisticated standards, which must be widely applicable and have credibility
      among the general practice profession. AIM: A study aimed to develop a range of
      criteria of prescribing quality, to set standards of performance for these
      criteria, and apply these standards to practices. METHOD: A consensus group
      consisting of eight general practitioners and a resource team was convened to
      develop and define criteria and set standards of prescribing performance using
      prescribing analyses and cost (PACT) data. The standards were applied to 1992-93
      prescribing data from all 518 practices in the former Northern Regional Health
      Authority. RESULTS: The group developed criteria and set numeric standards for 13
      aspects of prescribing performance in four areas: generic prescribing,
      prescribing within specific therapeutic groups, drugs of limited clinical value
      and standards based on prescribing volume. Except for generic prescribing,
      standards for individual criteria were achieved by between 9% and 34% of
      practices. For each criterion, a score was allocated based on whether the
      standard was achieved or not. Total scores showed considerable variation between
      practices. The distribution of scores was similar between fundholding and non
      fundholding practices, and also between dispensing and non-dispensing practices.
      CONCLUSION: Using a consensus group of general practitioners it is possible to
      agree criteria and standards of prescribing performance. This novel approach
      offers a professionally driven method for assessing the quality of prescribing in
      primary care.

PMID- 8745848
TI  - Use of the consultation satisfaction questionnaire to examine patients'
      satisfaction with general practitioners and community nurses: reliability,
      replicability and discriminant validity.
AB  - BACKGROUND: Primary health care services are the most frequently used in the
      health care system. Consumer feedback on these services is important. Research in
      this area relates mainly to doctor-patient relationships which fails to reflect
      the multidisciplinary nature of primary health care. AIM: A pilot study aimed to
      examine the feasibility of using a patient satisfaction questionnaire designed
      for use with general practitioner consultations as an instrument for measuring
      patient satisfaction with community nurses. METHOD: The questionnaire measuring
      patient satisfaction with general practitioner consultations was adapted for
      measuring satisfaction with contacts with a nurse practitioner, district nurses,
      practice nurses and health visitors. A total of 1575 patients in three practices
      consulting general practitioners or community nurses were invited to complete a
      questionnaire. Data were subjected to principal components analysis and the
      dimensions identified were tested for internal reliability and replicability. To
      establish discriminant validity, patients' mean satisfaction scores for
      consultations with general practitioners, the nurse practitioner, health visitors
      and nurses (district and practice nurses) were compared. RESULTS: Questionnaires
      were returned relating to 400 general practitioner, 54 nurse practitioner, 191
      district/practice nurse and 83 health visitor consultations (overall response
      rate 46%). Principal components analysis demonstrated a factor structure similar
      to that found in an earlier study of the consultation satisfaction questionnaire.
      Three dimensions of patient satisfaction were identified: professional care,
      depth of relationship and perceived time spent with the health professional. The
      dimensions were found to have acceptable levels of reliability. Factor structures
      obtained from data relating to general practitioner and community nurse
      consultations were found to correlate significantly. Comparison between health
      professionals showed that patients rated satisfaction with professional care
      significantly more highly for nurses than for general practitioners and health
      visitors. Patients' rating of satisfaction with the depth of relationships with
      health visitors was significantly lower than their ratings of this relationship
      with the other groups of health professionals. There were so significant
      differences between health professional groups regarding patients' ratings of
      satisfaction with the perceived amount of time spent with health professionals.
      CONCLUSION: The pilot study showed that it is possible to use the consultation
      satisfaction questionnaire for both general practitioners and community nurses.
      Comparison between health professional groups should be undertaken with caution
      as data were available for only a small number of consultations with some of the
      groups of health professionals studied.

PMID- 8745849
TI  - What do deans of medical schools and heads of departments of general practice
      think of preregistration rotations in general practice?
AB  - BACKGROUND: One general practice has offered preregistration rotations in general
      practice since 1981. Although popular with doctors who participate in the scheme,
      and considered a success by the associated teaching hospital, it remains the only
      established general practice rotation in the United Kingdom. AIM: A study was
      undertaken to assess the degree of interest in preregistration rotations in
      general practice expressed by medical school deans and heads of departments of
      general practice. METHOD: A questionnaire was sent to all 26 deans of medical
      schools and all 25 heads of departments of general practice of teaching hospitals
      in the UK that undertook clinical training. RESULTS: A total of 24 deans (92%)
      and 24 heads of departments of general practice (96%) replied to the
      questionnaire. The scheme was thought to be of value by 58% of deans and 79% of
      heads of departments of general practice. Half of the teaching hospitals thought
      that they might consider such a rotation in the next 3-5 years. The most
      frequently cited problem initiating such a scheme was financial. CONCLUSION:
      Given the current interest in medical teaching in the community, preregistration
      rotations in general practice deserve more attention.

PMID- 8745850
TI  - University departments of general practice: a changing scene.

PMID- 8745851
TI  - Care of patients with epilepsy in the community: will new initiatives address old
      problems?
AB  - Epilepsy is a serious neurological condition that has important medical,
      psychological and social consequences. Up to 90% of patients with epilepsy are
      not under hospital supervision at any one time; the role of the general
      practitioner is therefore of central importance. There seems little doubt that
      community care of people with epilepsy must be improved. This article reviews the
      research findings on the quality of care of people with epilepsy, examines the
      barriers to effective community care, and looks at local and national initiatives
      to improve the care of patients with epilepsy in the community. Finally, the
      review considers how care can best be provided in an efficient, effective and
      acceptable manner within the resources of present day general practice. A patient
      centred model is proposed that would tailor care to the needs of the individual
      patient.

PMID- 8745852
TI  - Improving continuing medical education and addressing the challenge of
      instituting reaccreditation.
AB  - The present postgraduate education allowance structure for general practitioners
      is unacceptable and inadequate on a number of counts. Improvements could be made
      in continuing medical education by involving learners more actively, through
      giving them greater ownership of their continuing medical education aims and by
      integrating it with the current moves towards reaccreditation. Current proposals
      for the implementation of reaccreditation are expensive, unacceptable to many in
      the general practice profession, and unconnected with present continuing medical
      education arrangements and the existing education structure. It would be more
      sensitive to current attitudes, more practical, a better use of existing
      facilities and more logical to improve continuing medical education by linking
      its improvement to the evaluation of reaccreditation in as acceptable and simple
      a way as possible. A framework is proposed, based on an annual educational
      general practitioner assessment visit in which a personal learning plan is
      developed as a focus for an individual's continuing medical education needs.

PMID- 8745853
TI  - Injury management by GPs in Australia.

PMID- 8745854
TI  - Postnatal sexual health.

PMID- 8745855
TI  - H pylori infection.

PMID- 8745856
TI  - Counselling and psychotropic drug prescribing.

PMID- 8745857
TI  - Warfarin for elderly patients.

PMID- 8745858
TI  - Management of opiate dependence.

PMID- 8745859
TI  - Balancing science and art in primary care research: past and present.

PMID- 8745860
TI  - General practitioners and public health doctors: sharing common goals?

PMID- 8745861
TI  - Clinical guidelines in primary care: a survey of general practitioners' attitudes
      and behaviour.
AB  - BACKGROUND: In the United Kingdom little is known about general practitioners'
      attitudes to and behaviour concerning clinical guidelines. AIM: A study was
      performed to investigate these two under-researched areas. METHOD: In 1994 a
      postal questionnaire on clinical guidelines was sent to all 326 general
      practitioner principals on the list of Lincolnshire Family Health Services
      Authority. The questionnaire consisted of 20 attitude statements and an open
      question on clinical guidelines, as well as surveying characteristics and
      behaviour of respondents. RESULTS: Of the 326 general practitioners sent
      questionnaires, 213 (65%) replied. Most respondents (78%) reported having been
      involved in writing inhouse guidelines. An even greater proportion (92%) reported
      having participated in clinical audit. Respondents were generally in favour of
      clinical guidelines, with mean response scores indicating a positive attitude to
      guidelines in 15 of the 20 statements, a negative attitude in four and
      equivocation in one. The majority of respondents felt that guidelines were
      effective in improving patient care (69%). Members (or fellows) of the Royal
      College of General Practitioners had a more positive attitude than non-members
      towards guidelines. They were also significantly more likely than non-members to
      have written inhouse guidelines, as were those who had participated in audit
      compared with those who had not participated in audit. A substantial minority
      (over a quarter) of general practitioners were concerned that guidelines may be
      used for setting performance-related pay, or that they may lead to 'cookbook'
      medicine, reduce clinical freedom or stifle innovation. There was also concern
      that guidelines should be scientifically valid. CONCLUSION: This study suggests
      that many general practitioners in the Lincolnshire Family Health Services
      Authority area have produced written inhouse guidelines. This is largely
      sustained by positive attitudes about the effectiveness and benefits of clinical
      guidelines. The positive attitude of RCGP members supports it in its continuing
      role in developing, implementing and evaluating guidelines in primary care. The
      question of whether incorporation of guidelines into clinical audit is an
      effective means to disseminate systematic research-based guidelines warrants
      further study.

PMID- 8745862
TI  - Investigation of benefits and costs of an ophthalmic outreach clinic in general
      practice.
AB  - BACKGROUND: With the advent of general practitioner fundholding, there has been
      growth in outreach clinics covering many specialties. The benefits and costs of
      this model of service provision are unclear. AIM: A pilot study aimed to evaluate
      an outreach model of ophthalmic care in terms of its impact on general
      practitioners, their use of secondary ophthalmology services, patients' views,
      and costs. METHOD: A prospective study, from April 1992 to March 1993, of the
      introduction of an ophthalmic outreach service in 17 general practices in London
      was undertaken. An ophthalmic outreach team, comprising an ophthalmic medical
      practitioner and an ophthalmic nurse, held clinics in the practices once a month.
      Referral rates to Edgware General Hospital ophthalmology outpatient department
      over one year from the study practices were compared with those from 17 control
      practices. General practitioners' assessments of the scheme and its impact on
      their knowledge and practice of ophthalmology were sought through a postal survey
      of all partners and interviews with one partner in each practice. Patient surveys
      were conducted using self-administered structured questionnaires. A costings
      exercise compared the outreach model with the conventional hospital ophthalmology
      outpatient clinic. RESULTS: Of 1309 patients seen by the outreach team in the
      study practices, 480 (37%) were referred to the ophthalmology outpatient
      department. The annual referral rate to this department from control practices
      was 9.5 per 10,000 registered patients compared with 3.8 per 10,000 registered
      patients from study practices. A total of 1187 patients were referred to the
      outpatient department from control practices. An increase in knowledge of
      ophthalmology was reported by 18 of 47 general practitioners (38%). Nineteen
      (40%) of 47 general practitioners took advantage of the opportunity for inservice
      training with the outreach team; they were more likely to change their routine
      practice for ophthalmic care or referral criteria for patients with cataracts or
      diabetes than those who did not attend for inservice training. The outreach
      scheme was popular with patients, for whom ease of access and familiarity of
      surroundings were major advantages. The cost per patient seen in the outreach
      clinics (48.09 pounds) was about three times the cost per patient seen in the
      outpatient department (15.71 pounds). CONCLUSION: The model of ophthalmic
      outreach care in this pilot study was popular with patients and general
      practitioners and appeared to act as an effective filter of demand for care in
      the hospital setting. However, the educational impact of the scheme was limited.
      Although the unit costs (per patient) of the outreach scheme compared
      unfavourably with those of conventional outpatient treatment, potential health
      gains from this more accessible model of care require further exploration.

PMID- 8745863
TI  - What type of general practice do patients prefer? Exploration of practice
      characteristics influencing patient satisfaction.
AB  - BACKGROUND: General practice is currently experiencing a large number of
      developments. Studies of patient satisfaction are required to guide the changes
      that many general practitioners are introducing. AIM: A study set out to examine
      the characteristics of general practices that influence patient satisfaction.
      METHOD: In 1991-92, a surgery satisfaction questionnaire of demonstrated
      reliability and validity was administered to 220 patients in each of 89 general
      practices. A further questionnaire completed by a member of practice staff
      collected information about practice characteristics including total list size,
      number, age and sex of practice partners, training status, fundholding status,
      presence of a practice manager and whether there was a personal list system.
      Stepwise multiple regression analyses were undertaken to identify those practice
      characteristics that influenced patient satisfaction. RESULTS: The mean of the
      response rates of patients completing questionnaires in each practice was 82%. An
      increasing total list size of patients registered with practices was associated
      with decreasing levels of general satisfaction and decreased satisfaction with
      accessibility, availability, continuity of care, medical care and premises. The
      presence of a personal list system was associated with increased levels of
      general satisfaction and increased satisfaction with accessibility, availability,
      continuity of care and medical care. Training practices were associated with
      decreased levels of general satisfaction and decreased satisfaction with
      availability and continuity of care. CONCLUSION: The patients of practices in
      this study preferred smaller practices, non-training practices and practices that
      had personal list systems. Practice organization should be reviewed in order to
      ensure that the trend towards larger practices that provide a wider range of
      services does not lead to a decline in patient satisfaction. General
      practitioners should have personal list systems and consider the creation of
      several personal teams within the practice consisting of small numbers of
      doctors, receptionists and practice nurses.

PMID- 8745864
TI  - COOP-WONCA charts: a suitable functional status screening instrument in acute low
      back pain?
AB  - BACKGROUND: Functional status is considered an important measure of health status
      in primary care. The COOP-WONCA charts, which comprise six single-item scales,
      have mainly been used to determine functional ability in chronically ill
      patients. AIM: A study was carried out to determine whether the charts are able
      to measure the degree of functional impairment associated with acute illness and
      the improvement in functional ability accompanying the process of recovery.
      METHOD: A total of 95 patients presenting with acute low back pain were recruited
      from 15 single-handed general practices in northern Germany. At presentation and
      at two-week follow up, these patients completed self-administered questionnaires
      which included the COOP-WONCA charts. The charts ask patients to use the
      timescale of the past two weeks when rating their condition. Baseline and follow
      up measurements of the charts were compared and correlations of chart scores with
      patients' measurements of pain intensity on a visual analogue scale, general
      practitioners' ratings of impairment and patients' measurements of recovery were
      analysed. RESULTS: Only the chart measuring change in health revealed a
      deterioration in functional ability associated with the onset of pain and an
      improvement in functional status at follow up. Two of the other charts indicated
      a deterioration at follow up. Only the chart measuring change in health was
      correlated with ratings of pain and impairment at baseline. At follow up, strong
      correlations were found between general practitioners' assessments of impairment,
      patients' ratings of pain and patients' ratings of recovery for all scales except
      for those measuring social activities and daily activities. The patients
      interpreted the instructions for using the COOP-WONCA charts differently; some
      included the period of acute back pain while others did not. CONCLUSION: Of the
      six charts only the change in health chart proved to be a suitable scale for
      measuring short-term changes in functional ability among general practice
      patients with acute low back pain. This may partly be a result of patients
      misunderstanding the instructions. If the COOP-WONCA charts are used with acutely
      ill patients, the fixed two-weeks timescale is not appropriate. It is suggested
      that patients consider their present complaints when rating their condition.

PMID- 8745865
TI  - The carrot, the stick and the general practitioner: how have changes in financial
      incentives affected health promotion activity in general practice?
AB  - BACKGROUND: Financial incentives for increasing health promotion activity in
      primary care, introduced with the 1990 contract for general practitioners, were
      amended in 1993 and are now focused on cardiovascular disease. Payments for
      health promotion clinics were abolished and target payments were introduced. AIM:
      The study aimed to evaluate the effect of the change, in June 1993, in financial
      incentives for health promotion activity in primary care on the distribution of
      health promotion payments in two family health services authorities. METHOD: A
      retrospective study was undertaken in which data from two family health services
      authorities were used to determine the annual level of health promotion payments
      per 1000 practice population before and after the contractual amendment. Health
      promotion clinic payment data were analysed for 78 practices in Bedfordshire
      Family Health Services Authority and 85 practices in Kensington, Chelsea and
      Westminster Family Health Services Authority. Changes in health promotion
      payments were calculated and related to two measures of relative need: all cause
      standardized mortality ratios, for patients aged 74 years or less, of the
      electoral ward in which the practice is located; and the Jarman underprivileged
      area score. High relative need was defined as a standardized mortality ratio of
      over 100 or more than 25% of the practice population living in electoral wards
      with a Jarman score of over 30. RESULTS: Health promotion payments were more
      evenly distributed after the change in June 1993 than before between the two
      family health services authorities and between general practices. Single-handed
      practices were carrying out more clinics in 1992 than multi-partner practices and
      consequently were one of the greatest financial losers as a result of the change.
      In addition, practices located in electoral wards with high relative needs lost
      proportionally more than those in electoral wards with lower needs. CONCLUSION:
      Changes in the general practitioner health promotion contract have created new
      financial winners and losers. It now appears that health promotion payments are
      more evenly distributed but that the distribution is unrelated to need or
      treatment given. More evidence on the effectiveness of health promotion
      interventions is required before policies aimed at promoting better health
      through primary care can be fully evaluated.

PMID- 8745867
TI  - Telephone consultations in general practice: an additional or alternative
      service?
AB  - BACKGROUND: There is conflicting evidence about whether telephone consultations
      in general practice represent additional or alternative contacts with the general
      practitioner. AIM: A study set out to assess the characteristics of patients
      using the telephone to consult the general practitioner and whether telephone
      consultations were used as an additional or an alternative service to surgery
      consultations during surgery hours. METHOD: The study took place in one practice
      that has run a 'phone-in clinic' for five years. A questionnaire on perceptions
      of and attitudes towards telephone consultations was sent to 259 patients who
      consulted the general practitioner by telephone and to an age-sex matched group
      of patients whose medical records indicated that they had never consulted the
      general practitioner by telephone. For both groups, numbers of repeat
      prescriptions and consultations in the preceding year were determined from
      medical records. RESULTS: Those who consulted the doctor by telephone were
      significantly more likely to be aware of the phone-in clinic, to have a telephone
      at home, to have children aged under five years at home and to be receiving
      repeat prescriptions and repeat prescriptions for psychotropic drugs compared
      with those who had never consulted by telephone. Eleven of 226 patients who
      consulted be telephone (5%) indicated that they would definitely not have made a
      surgery appointment or home visit request (that is, they represented additional
      general practitioner workload) while 120 (53%) used the telephone consultation as
      an alternative to making a surgery appointment and 22 (10%) used the telephone
      consultation as an alternative to requesting a home visit. CONCLUSION: It appears
      that the telephone service was being used largely as an alternative access point
      to the doctor. General practitioners should not be apprehensive about the
      possible increase in workload generated by introducing telephone consultations,
      for example in phone-in clinics.

PMID- 8745866
TI  - Who should give lifestyle advice in general practice and what factors influence
      attendance at health promotion clinics? Survey of patients' views.
AB  - BACKGROUND: Health promotion activity in general practice has increased greatly
      since 1990. A large proportion of this work is undertaken by practice nurses.
      Little is known about patients' views about the providers of health promotion or
      their views about general practice health promotion clinics. AIM: A study was
      carried out in 1992 to determine patients' views about the provision of health
      promotion advice by general practitioners and practice nurses and their views
      about attending health promotion clinics. METHOD: A postal questionnaire was sent
      to a random sample of 1750 patients aged 16 years and over from five general
      practices in south Tyneside. The questionnaire explored patients' preferences
      regarding health promotion advice from the general practitioner or practice nurse
      in relation to four areas of lifestyle advice and factors that might encourage
      patients to attend a health promotion clinic. RESULTS: A response rate of 75% was
      obtained from 1639 eligible patients. Receiving health promotion advice from
      either the general practitioner or the practice nurse was the most commonly
      preferred option expressed by patients overall. The ability of health promotion
      clinic staff to deal with patients' concerns about their illness and short
      waiting times were more likely to influence patients' attendance at health
      promotion clinics than the presence of a general practitioner or practice nurse.
      CONCLUSION: In the present study, many patients found health advice received from
      practice nurses and general practitioners equally acceptable. However, it was the
      ability of health professionals to respond to patients' health concerns in the
      health promotion clinic rather than the type of health professional running the
      clinic that was important for patients.

PMID- 8745868
TI  - General practitioner reaccreditation: use of performance indicators.
AB  - There has been increasing debate about reaccreditation of general practitioners
      over the last few years with contributions from the General Medical Services
      Committee, the Royal College of General Practitioners and the National
      Association of Health Authorities and Trusts. The implications of proposals in
      terms of cost, logistics and organization are discussed in this paper, in light
      of experience with the introduction of summative assessment for general
      practitioner registrars (trainees) and a programme of training practice visits in
      West Midlands Region. A model for reaccreditation for all general practitioners
      is proposed which is professionally led and sensitive to the needs of patients
      and health service managers. The basic proposition is that publicly owned family
      health services authority data could be used as initial performance indicators
      for professional competence. The model is dependent on the rebuttal of the null
      hypothesis: there is no link between the competence of a general practitioner and
      his or her achievements in the suggested performance indicators. If the
      performance indicators (educational commitments, prescribing data, health
      promotion activity and immunization targets, and service elements) can be shown
      to correlate with possession of the attributes for independent practice as
      defined by the General Medical Council, then a relatively inexpensive and simple
      system of reaccreditation could be envisaged. General practitioners who are
      recorded as achieving set performance indicator targets would be accorded
      automatic reaccreditation. Only substandard practitioners would be required to be
      assessed further by a visiting team of local general practitioner peers and, if
      appropriate, a remedial education strategy introduced. This method would
      complement the General Medical Council scheme for assessing an individual
      doctor's persistent poor performance, which could then be invoked as a last
      resort.

PMID- 8745870
TI  - Folic acid in pregnancy.

PMID- 8745869
TI  - Optimizing inhaled drug delivery in patients with asthma.
AB  - Successful management of asthmatic patients depends on achieving adequate
      delivery of inhaled drugs to the lung. This assumes particular importance for
      inhaled corticosteroids where the therapeutic goal should be to achieve a high
      ratio of airway anti-inflammatory efficacy to local and systemic side effects.
      The availability of user-friendly inhaler devices requires a critical appraisal
      of their effectiveness and an evaluation of whether improved lung deposition of
      anti-asthma drugs translates into improved clinical efficacy. There is evidence
      to suggest that the routine use of large-volume spacers for inhaled
      corticosteroids may not be the best first-line option, in that reduced drug
      delivery is associated with multiple actuations, inhalation delay and the
      presence of static electricity. Breath-actuated pressurized aerosol devices or
      dry powder inhaler devices may be a better option for many asthmatic patients,
      although the efficiency of drug delivery varies considerably between these
      devices. There is good evidence with a reservoir dry powder inhaler device to
      show that improved lung deposition translates into better therapeutic response,
      both in terms of beta 2-agonist and corticosteroid delivery. For inhaled
      corticosteroids, such as fluticasone propionate and budesonide, there is evidence
      to show that systemic bioactivity is mainly determined by lung bioavailability
      rather than gastrointestinal bioavailability, because of the absence of first
      pass metabolism of these drugs in the lung. There is also evidence to show that
      the greater glucocorticoid potency of fluticasone propionate translates directly
      into greater systemic bioactivity, but not into enhanced efficacy, at doses above
      1 mg daily. The use of efficient delivery systems, such as the reservoir dry
      powder inhaler device, may not only improve control of asthma and compliance with
      therapy, but may also allow dose reduction ('step-down' therapy) and hence may
      possibly reduce overall prescribing costs in the long term.

PMID- 8745871
TI  - Management of opiate dependence.

PMID- 8745872
TI  - Bereavement care.

PMID- 8745873
TI  - Counselling and psychotropic drug prescribing.

PMID- 8745874
TI  - Information leaflets on contraception.

PMID- 8745875
TI  - Diphtheria.

PMID- 8745876
TI  - Practice nurse workload.

PMID- 8745877
TI  - Re-education via Darwinian medicine.

PMID- 8745878
TI  - Lymphatic and venous function in lipoedema.
AB  - Lipoedema is a common but infrequently recognized condition causing bilateral
      enlargement of the legs in women. Although generally considered to be the result
      of an abnormal deposition of subcutaneous fat with associated oedema, the precise
      mechanisms responsible for oedema formation have yet to be fully established. In
      order to evaluate the possible role of lymphatic or venous dysfunction in the
      pathogenesis of lipoedema, 10 patients were investigated by photoplethysmography
      (venous function) and quantitative lymphoscintigraphy (lymphatic function). The
      results were compared with those from patients with primary lymphoedema and those
      from healthy volunteers. The results demonstrated minor abnormalities of venous
      function in only two patients. One patient had moderately impaired lymphatic
      function in both legs and seven patients had a marginal degree of impairment in
      one or both legs. However, in none of these cases did the impairment attain the
      low levels seen in true lymphoedema. Lipoedema appears to be a distinct clinical
      entity best classified as a lipodystrophy rather than a direct consequence of any
      primary venous or lymphatic insufficiency.

PMID- 8745879
TI  - UVB therapy decreases the adhesive interaction between peripheral blood
      mononuclear cells and dermal microvascular endothelium, and regulates the
      differential expression of CD54, VCAM-1, and E-selectin in psoriatic plaques.
AB  - A dermal lymphocytic infiltrate is a characteristic feature of psoriasis, and may
      be involved in the pathogenesis of the disease. We have previously shown that
      specialized dermal microvascular endothelial cells (DMEC) in psoriatic lesions
      promote the selective adherence of the CD4 CD45Ro helper T-cell subset. In this
      study, we examined the adhesive interaction between peripheral blood mononuclear
      cells and psoriatic DMEC in patients treated with ultraviolet B light (UVB), and
      correlated the results with the expression and function of endothelial adhesion
      molecules on DMEC. Seven psoriatic patients were exposed to one MED of UVB daily
      for 14 days, and the binding properties of their peripheral blood mononuclear
      cells (PBMC), and tissue specimens taken from their lesions on days 0, 2, 3, 6,
      8, 11 and 14 of UVB treatment, were studied. The ability of psoriatic PBMC to
      adhere to non-irradiated control or UVB-treated psoriatic plaques was reduced by
      70% after treatment with 2-3 MED, and complete inhibition was obtained after 8-11
      MED. In contrast, exposure of psoriatic plaques to 2-3 MED had no effect on the
      capacity of DMEC to support normal PBMC binding, which was only reduced after 8
      11 MED. In addition, psoriatic plaques which were shielded from direct UVB
      exposure also showed decreased PBMC binding, suggesting a systemic effect of UVB
      treatment. Immunoperoxidase staining revealed that CD54 (ICAM-1) and E-selectin
      were strongly expressed on dermal vessels in untreated psoriatic plaques.
      Treatment of patients with 6-8 MED significantly decreased CD54 and E-selectin
      expression. In contrast, VCAM-1 expression on untreated plaques was weaker than
      that of CD54 and E-selectin, but was markedly induced following UVB treatment. In
      functional blocking studies, preincubation of tissue from untreated psoriatic
      plaques with anti-E-selectin antibody, but not antibodies against CD54 and VCAM
      1, significantly inhibited the ability to bind normal PBMC. These observations
      suggest that UVB treatment interferes with the adhesive properties of both
      psoriatic PBMC and endothelial cells, and differentially regulates the expression
      of endothelial adhesion molecules. The study also provided direct evidence for
      the involvement of E-selectin in the adhesion of circulating lymphocytes to
      psoriatic endothelial cells.

PMID- 8745880
TI  - Soluble E-selectin in sera of patients with atopic dermatitis and psoriasis-
      correlation with disease activity.
AB  - E-selectin endothelial leucocyte adhesion molecule-1 is expressed on endothelial
      cells in distinct inflammatory skin diseases. E-selectin mediates the adhesion
      between activated endothelium and different inflammatory cells. To evaluate
      soluble E-selectin as a marker of disease activity in patients with atopic
      dermatitis and psoriasis, the concentration of soluble E-selectin, determined by
      ELISA, was studied in sera of patients before and after treatment and compared
      with normal non-atopic controls. The disease severity was established using
      clinical scoring systems. Levels of soluble E-selectin were significantly
      elevated in sera of patients with atopic dermatitis and psoriasis (as compared
      with controls). Clinical improvement, after treatment, in patients with atopic
      dermatitis, but not in psoriasis, was associated with a significant decrease in
      serum levels of soluble E-selectin. There was a significant correlation of
      soluble E-selectin and disease activity in patients with atopic dermatitis. These
      data indicate that soluble E-selectin is another parameter to evaluate the
      inflammatory response in atopic dermatitis and psoriasis. Determination of
      soluble E-selectin may be a useful measure of disease activity in atopic
      dermatitis.

PMID- 8745881
TI  - Human epidermal Langerhans cells express the ICAM-3 molecule. Immunohistochemical
      and immunoelectron microscopical demonstration.
AB  - Three ligands have been described for the leucocyte integrin LFA-1, namely
      intercellular adhesion molecule (ICAM)-1, ICAM-2, and ICAM-3. ICAMs show
      differences in tissue distribution and inducibility. The recently described ICAM
      3 is highly expressed on resting lymphocytes, monocytes and neutrophils. Here, we
      demonstrate that the whole human epidermal Langerhans cell (LC) population
      expresses this molecule. Immunohistochemical staining of skin sections with an
      anti-ICAM-3 monoclonal antibody displayed reactivity with dendritic epidermal
      cells regularly distributed along the epidermis. Highly-sensitive immunoelectron
      microscopy procedures, performed on freshly suspended epidermal cells both at
      transmission and scanning electron microscopic levels, enabled demonstration that
      the whole LC population expresses cell surface ICAM-3. In contrast, keratinocytes
      and melanocytes were consistently negative. The prominent expression of ICAM-3 by
      resident LC could imply a crucial part for this molecule in leucocyte
      intercellular interactions in the skin.

PMID- 8745882
TI  - Expression of E-cadherin in human epidermal non-melanoma cutaneous tumours.
AB  - E-cadherin is a calcium-sensitive, cell-to-cell, adhesion molecule that is
      expressed widely in normal human epithelial tissue. Abnormal expression has been
      described in colorectal, breast and nasopharyngeal squamous cell carcinomas,
      where loss of E-cadherin is associated with an increased metastatic potential. We
      have examined, by standard immunohistochemical techniques using the monoclonal
      antibody HECD-1 (E-cadherin monoclonal antibody), the distribution of E-cadherin
      in normal human skin and in non-melanoma neoplastic lesions. In the normal
      epidermis, E-cadherin was strongly expressed on the surface of keratinocytes and
      specialized epithelial structures. Staining was absent from the lower pole of
      basal keratinocytes in contact with the basement membrane. Weak cytoplasmic
      staining was also noted in basal keratinocytes. No reactivity was demonstrated in
      dermal structures. The assessment of cutaneous tumours demonstrated an altered
      pattern of staining in most cases. Cell surface expression was reduced in 28 of
      30 cases of basal cell carcinomas (BCC). Twenty showed an additional feature of
      positive staining on the dermal aspect of peripheral cells of tumour lobules. In
      squamous cell carcinomas (SCC) (n = 16), surface expression was attenuated in
      eight and absent in a further four. Strong surface expression, similar to normal
      skin was seen in all examples of Bowen's disease (n = 6), viral wart (n = 3),
      seborrhoeic keratosis (n = 3) and actinic keratosis (n = 4). This study
      demonstrates that, in BCC and SCC, but not in premalignant lesions, cell-surface
      expression of E-cadherin is reduced, consistent with the observation that the
      loss of E-cadherin is associated with tumour invasion.

PMID- 8745883
TI  - The expression of integrin alpha 2 beta 1 and attachment to type I collagen of
      melanoma cells are preferentially induced by tumour promoter, TPA (12-O
      tetradecanoyl phorbol-13-acetate).
AB  - The adhesion of melanoma cells to the extracellular matrix (ECM) protein is
      likely to be essential in their invasive metastatic processes. Treatment with 12
      O-tetradecanoyl phorbol-13-acetate (TPA), a potent protein kinase C (PKC)
      activator, preferentially induced the expression of alpha 2 beta 1 integrin, the
      receptor for collagen/laminin. The number of cells attached to type I collagen,
      but not laminin, was increased by treatment with TPA. Prior exposure to PKC
      inhibitors such as H-7 (20 mumol/l) and calphostin C (50 mumol/l) had no effect
      on TPA-induced alpha 2 beta 1 integrin expression and cell attachment to type I
      collagen, whereas prior exposure to the calmodulin antagonist W-7(50 mumol/l)
      inhibited these TPA-induced events. The augmented adhesion was also inhibited by
      anti-alpha 2 antibody. These data suggest that the increased attachment of
      melanoma cells to type I collagen appears to be mediated by the preferential
      augmentation of integrin alpha 2 beta 1, and the activation of calmodulin kinase,
      but not via the activation of PKC. Analysis of the expression of integrins and of
      cell attachment to ECMs is important in elucidating the mechanisms involved in
      the progression and metastasis of malignant melanoma.

PMID- 8745884
TI  - Flow cytometric DNA content analysis on squamous cell carcinomas according to the
      preceding lesions.
AB  - DNA-ploidy in primary cutaneous squamous cell carcinomas which had developed from
      different preceding clinical lesions was examined by flow cytometry using
      paraffin-embedded blocks. DNA-aneuploidy was detected in none of 15 squamous cell
      carcinomas arising from a burn scar. On the other hand, 12 of 26 squamous cell
      carcinomas arising from sun-damaged skin in the elderly, and two of four arising
      from chronic radiodermatitis, showed aneuploid patterns. A significantly higher
      incidence of DNA-aneuploidy was observed in squamous cell carcinomas arising from
      sun-damaged skin than those from a burn scar (P < 0.01); the mean diameter size
      of the former was significantly smaller than that of the latter (P < 0.0001). The
      mean age of patients with aneuploid tumours (74.2 +/- 9.2: years +/- standard
      deviation (SD)) was significantly higher than that with diploid tumours (64.1 +/-
      13.8) (P < 0.01).

PMID- 8745885
TI  - Expression of the CD34 antigen distinguishes Kaposi's sarcoma from pseudo
      Kaposi's sarcoma (acroangiodermatitis).
AB  - The differential diagnosis between Kaposi's sarcoma and the so-called 'pseudo
      Kaposi's sarcoma' or acroangiodermatitis of the feet is often fraught with
      difficulty, not only on clinical but also on histological grounds. The aim of
      this study was to assess whether immunolabelling for the CD34 antigen, a marker
      of Kaposi's sarcoma cells, could be of value in the distinction between these two
      angioproliferative disorders. We comparatively examined 16 biopsy specimens from
      cases of Kaposi's sarcoma and seven biopsies from patients with pseudo-Kaposi's
      sarcoma, by a streptavidin-biotin-peroxidase method, using a monoclonal antibody
      to the CD34 antigen. All cases of Kaposi's sarcoma showed CD34 labelling both on
      endothelial cells and on the characteristic spindle-shaped, perivascular cells.
      Biopsies of pseudo-Kaposi's sarcoma showed a strong labelling of endothelial
      cells of hyperplastic vessels. However, in sharp contrast with Kaposi's sarcoma,
      a complete absence of perivascular CD34 expression was noted. It seems therefore
      that immunolabelling for the CD34 antigen appears to be a valuable tool in the
      differential diagnosis between Kaposi's sarcoma and pseudo-Kaposi's sarcoma.

PMID- 8745886
TI  - Periodicity in the growth and shedding of hair.
AB  - Ten men, with or without alopecia, were observed for a period of between 8 and 14
      years using phototrichograms on a precisely located zone on the vertex of the
      scalp. Among the various parameters observed, we chose the percentage of hairs in
      telogen as the criterion for assessment of hair shedding. Mathematical analysis
      of the variations in this telogen percentage was carried out for each individual
      subject and for the whole group, as represented by the population mean (or the
      'average subject'). This analysis demonstrated the existence of overall annual
      periodicity, manifested by a maximal proportion of telogen hairs at the end of
      summer and the beginning of autumn. Some subjects also exhibited a periodicity
      approximately corresponding to two annual peaks. In those subjects with a very
      low proportion of hairs in telogen, no periodicity was demonstrated. In another
      group of subjects, it has been shown that the variations in telogen percentage
      reflect those observed in hair shedding, assessed in a standardized manner.
      Periodicity of the telogen percentage, and hence of hair fall, is not independent
      of climatic factors (sunshine hours), and these must be taken into account when
      assessing the treatment or prevention of hair loss.

PMID- 8745887
TI  - The DEBR rat, alopecia areata and autoantibodies to the hair follicle.
AB  - Many attempts have been made to implicate hair follicle-specific autoantibodies
      in the pathogenesis of alopecia areata (AA), a suspected autoimmune disease.
      Using the DEBR rat model for AA, we developed a refined indirect
      immunofluorescent technique to examine the sera from individual rats for the
      presence of autoantibodies to the hair follicle and to other tissues. Sera were
      tested on cryostat sections from normal PVG/Ola rats and DEBR rats. We found that
      DEBR sera contained IgG autoantibodies specific for hair follicle epidermal
      differentia. While individual sera revealed detailed differences, the target
      tissues identified were hair cortex and cuticle and the inner root sheath,
      especially the Henle's layer. Some sera also contained autoantibodies specific
      for skeletal muscle and nuclear components. Of 10 young prelesional rats with
      apparently normal coats of hair, three had hair follicle autoantibodies and seven
      had skeletal muscle autoantibodies. Nine of 10 active lesional rats with
      progressing hair loss had follicle autoantibodies and four had skeletal muscle
      autoantibodies. All 10 established lesional rats had follicle autoantibodies and
      one had muscle autoantibodies. Control sera from eight PVG/Ola rats showed no
      specific positive staining for hair follicle components or other tissues.
      Autoantibodies to intracellular hair follicle differentiation products were
      readily detected in DEBR rat sera. As these antibodies appeared to be generated
      after the appearance of the mononuclear follicular infiltrate, such
      autoantibodies may be a secondary effect. We conclude that, while the presence of
      autoantibodies in the DEBR rat model is associated with autoimmune activity,
      their role in the pathogenic progression of AA has yet to be ascertained.

PMID- 8745888
TI  - The Mexican hairless dog as a model for assessing the comedolytic and morphogenic
      activity of retinoids.
AB  - The skin of the Mexican hairless dog is covered with comedones, and this animal
      therefore provides a potentially useful model to assess the comedolytic activity
      of topical anti-acne drugs. We treated an animal with three different
      formulations of tretinoin for a 14-week period, and all produced a similar
      clinical response. There was a striking reduction in the number of comedones, and
      the skin became lighter and more uniform in colour. Histological changes were
      similar to those reported in humans treated with tretinoin, but a novel finding
      was incomplete neogenesis of hair follicles. We suggest that the Mexican hairless
      dog may be a useful model for screening novel molecules for retinoid activity.

PMID- 8745889
TI  - Prolonged treatment with oral retinoids in adults: no influence on the frequency
      and severity of spinal abnormalities.
AB  - It is generally accepted that the spine is the site of predilection for retinoid
      induced skeletal abnormalities. However, the reported prevalence of skeletal
      problems varies widely. To investigate the frequency and severity of retinoid
      induced spinal abnormalities, all records of patients who underwent spinal
      radiographs at the request of the department of dermatology between 1983 and 1993
      were reviewed. This group of 135 patients comprised the total population of
      retinoid-treated patients and those patients who were investigated for possible
      future retinoid treatment. The mean treatment period in the total group was 30
      months and the mean cumulative dose of retinoid was 31 g. In 50 patients the
      treatment period was > or = 24 months with 30 patients being treated for more
      than 48 months. Baseline radiographs were available from 26 patients and these
      were compared with the most recent X-rays during treatment. The mean treatment
      period in this 'prospective group' was 25 months and the mean cumulative dose of
      retinoid was 25 g. The prevalence of diffuse idiopathic skeletal hyperostosis
      (DISH), degenerative changes and osteoporosis in the total group was respectively
      16%, 53% and 29%. There was no statistically significant relation between the
      duration of treatment or the cumulative dose and the prevalence or severity of
      DISH, degenerative changes and osteoporosis. Only the age of the patients was
      significantly related to the frequency and severity of skeletal abnormalities. In
      the 'prospective group', again, no important changes were observed between the
      radiographs at baseline and during treatment. In this study no relation
      whatsoever between spinal abnormalities and prolonged oral retinoid treatment
      could be established. The performance of annual routine spinal radiographs during
      retinoid treatment is not necessary in our opinion. Additional controlled and
      prospective studies on spinal and extraspinal skeletal abnormalities are required
      to develop definitive screening guidelines for patients submitted to long-term
      retinoid treatment.

PMID- 8745890
TI  - UVA-induced immune suppression in human skin: protective effect of vitamin E in
      human epidermal cells in vitro.
AB  - UVA (320-400 nm) radiation damage to membranes, proteins, DNA and other cellular
      targets is predominantly related to oxidative processes. In the present study, we
      demonstrated that cutaneous UVA-induced immunosuppression can be related, at
      least in part, to the appearance of these oxidative processes. The UVA-induced
      oxidative processes in freshly isolated epidermal cells were monitored by
      measuring the thiobarbituric acid reactive substances (TBARS) as an index of
      peroxidation. The in vitro immunosuppressive effects of UVA were demonstrated by
      measuring the allogeneic lymphocyte proliferation induced by epidermal cells or
      purified Langerhans cells in the mixed epidermal cell-lymphocyte reaction
      (MECLR). In addition, the effects of a potent antioxidant (vitamin E) on these
      two UVA-induced processes were analysed. Our results showed that the antigen
      presenting function of Langerhans cells measured in the MECLR is dose-dependently
      decreased by UVA radiation (up to 20J/cm2). Overnight incubation of epidermal
      cells with vitamin E (400 mumol/l) before irradiation partially protected
      epidermal cells from the immunosuppressive effects of UVA radiation, and
      decreased TBARS release into the supernatant (a decrease of 35% compared with a
      control without vitamin E). Our results suggest that UVA radiation may alter cell
      presenting antigen function partly via the generation of reactive oxygen species
      which trigger peroxidative processes, and these data contribute to the
      understanding of the role of oxidative mechanisms in immune suppression induced
      by UVA radiation. Our in vitro model can be used to quantify UV-mediated
      epidermal cell damage and the degree of immune photoprotection provided by
      various agents.

PMID- 8745891
TI  - Immunological studies of herpes simplex virus infection in children with atopic
      eczema.
AB  - This study examines the role of immune defence mechanisms in herpes simplex virus
      (HSV) infections in atopic eczema and whether impairment of these mechanisms
      explains the susceptibility of some children with atopic eczema to cutaneous HSV
      infections. Ten children with eczema herpeticum and 13 with atopic eczema and
      recurrent HSV infection affecting multiple skin sites were studied, together with
      relevant control groups. In all children with atopic eczema, in vitro
      lymphoproliferation in response to stimulation with concanavalin A (Con A) was
      significantly decreased and natural killer (NK) cells (CD16 + 56) were reduced
      compared with non-atopic controls. IL-2 receptors, a marker for lymphocyte
      activation, were decreased during the acute phase of eczema herpeticum, and for 1
      month thereafter. A positive stimulation index (> 3) to HSV antigen, and high HSV
      IgG antibody titres measured by ELISA, Western blotting and neutralization assay,
      were seen in children with eczema herpeticum by 6 weeks, and also in children
      with atopic eczema and recurrent HSV infections. No evidence of an HSV-specific
      immune defect (either cell-mediated or humoral) was found in atopic eczema.
      Impairment of cell-mediated immunity in atopic eczema was suggested by the
      reduced response to Con A. It is likely that reduced numbers of circulating NK
      cells and a decrease in IL-2 receptors during early eczema herpeticum contribute
      to the susceptibility of children with atopic eczema to cutaneous HSV infections.

PMID- 8745892
TI  - Histamine release in skin monitored with the microdialysis technique does not
      correlate with the weal size induced by cow allergen.
AB  - The purpose of this study was to monitor histamine release in immediate-type
      hypersensitivity reactions in the skin of 10 atopic patients, sensitive to cow,
      by using the microdialysis technique. Three healthy subjects, without any atopic
      features or background, served as the control group. The probe inserted into the
      forearm dermal skin was perfused with isotonic saline solution. Samples were
      collected at 15-min intervals. After the first allergen challenge of four prick
      tests close to the probe with cow allergen extract, the skin was similarly
      repricked again in five patients and three healthy subjects, and in five other
      patients, 25 microliters of 10 mumol/l substance P (SP) was injected
      intracutaneously. The samples were analysed for histamine by radioenzyme assay.
      The patients were clinically evaluated for allergic symptoms, prick- and scratch
      patch test reactivity and for serum cow-specific, and total, IgE levels. The
      baseline histamine concentration was 7.5 +/- 4.0 nmol/l (mean +/- standard
      deviation: SD; n = 10). After the allergen challenge, the histamine concentration
      in the consecutive samples was 11.9 +/- 11.0 nmol/l, 91.1 +/- 127.3 nmol/l, 61.0
      +/- 94.2 nmol/l and 33.7 +/- 53.7 nmol/l. The peak concentration was detected in
      the 15-30 min fraction, and it varied between 0 and 406 nmol/l regardless of the
      weal size. The second allergen challenge was unable to induce marked additional
      histamine release, but SP induced extensive histamine liberation in those
      patients who did not exhibit histamine release during the preceding prick tests.
      In three healthy subjects, the baseline histamine concentration was 6.2 +/- 3.9
      nmol/l. After the allergen challenge, no additional histamine liberation could be
      measured. Surprisingly, the histamine release was not related to the size of the
      cow-induced weal nor was it related to any specific allergic symptoms or IgE
      levels. The results suggest that, in some patients, mast cell mediators other
      than histamine play a significant part in immediate-type allergic reactions of
      skin.

PMID- 8745893
TI  - Dietary factors and the risk of psoriasis. Results of an Italian case-control
      study.
AB  - We have conducted a case-control study to explore the relation between the
      consumption of selected foods and psoriasis. The out-patient services of nine
      teaching hospitals and five general hospitals in northern and southern Italy took
      part. Cases were newly diagnosed psoriatics with a history of skin problems of no
      more than 2 years. As controls, we selected subjects with newly diagnosed skin
      conditions, other than psoriasis, who were seen in the same out-patient clinics.
      Inclusion of cases and controls was limited to the age group 16-65 years. A total
      of 316 psoriatics and 366 controls were recruited. Anthropometric measures,
      including height and weight, were obtained. Diet was assessed by a
      semiquantitative food frequency questionnaire. Psoriasis appeared to be
      positively associated with body mass index (chi 2(1) trend 4.3, P < 0.05).
      Significant inverse relations with psoriasis were also observed for the intake of
      carrots (chi 2(1) trend 4.8, P < 0.05), tomatoes (chi 2(1) trend 26.3, P < 0.01),
      fresh fruit (chi 2(1) trend 11.7, P < 0.01) and index of beta-carotene intake
      (chi 2(1) trend 9.1, P < 0.01). Although largely explorative, these results
      provide some evidence for a potential role of diet in psoriasis.

PMID- 8745894
TI  - The effects of acne treatment with a combination of benzoyl peroxide and
      erythromycin on skin carriage of erythromycin-resistant propionibacteria.
AB  - Concomitant application of 5% w/w benzoyl peroxide and 3% w/w erythromycin has
      previously been shown to prevent the overgrowth, on the skin of acne patients, of
      erythromycin-resistant coagulase-negative staphylococci, which occurs when the
      antibiotic is used alone. Two in vivo studies were carried out to assess the
      ability of the same therapeutic combination to inhibit the growth of pre-existing
      erythromycin-resistant propionibacteria and to prevent the selection of resistant
      strains during treatment. A double-blind clinical trial in 37 patients with mild
      to moderate acne vulgaris showed that the combination brought about a > 3 log10
      c.f.u. reduction in total propionibacterial numbers/cm2 after 6 weeks therapy (P
      < 0.001, Wilcoxon's matched pairs) and also significantly reduced the number of
      erythromycin-resistant propionibacteria (P < 0.05). In contrast, erythromycin
      alone reduced the total propionibacterial count by < 1.5 log10 c.f.u./cm2 after 6
      weeks (P < 0.05) and did not affect the number of erythromycin-resistant strains.
      The combined formulation was significantly more effective at reducing total
      propionibacterial numbers at 6 (P < 0.01, Mann-Whitney) and 12 weeks (P < 0.05)
      than erythromycin alone, although, after 12 weeks, the anti-propionibacterial
      efficacy of both preparations was less marked. Five patients on combination
      therapy, and five treated with erythromycin alone, acquired erythromycin
      resistant strains de novo at week 6 or week 12. In an open study in 21 acne
      patients, who each carried > 10(3) c.f.u. erythromycin-resistant
      propionibacteria/cm2 skin pretreatment, the combination of erythromycin and
      benzoyl peroxide reduced the total propionibacterial count by > 2.5 log10 and the
      number of erythromycin-resistant strains by a similar amount (P < 0.001,
      Wilcoxon). This was accompanied by highly significant reductions in acne grade
      and lesion counts (P < 0.001). These data suggest that the combination of 5% w/w
      benzoyl peroxide and 3% w/w erythromycin has greater in vivo anti
      propionibacterial activity than 3% w/w erythromycin alone, and brings about
      significant clinical improvement in acne patients with high numbers of
      erythromycin-resistant propionibacterial strains pretreatment.

PMID- 8745895
TI  - Pemphigus in Mali: a study of 30 cases.
AB  - Pemphigus has been largely studied in developed countries (North America and
      Europe) and in Brazil. In these geographical settings, pemphigus presents two
      very different epidemiological and clinical patterns. Little is known about
      pemphigus in other regions of the world, particularly in Africa. We report here a
      study of 30 cases of pemphigus observed in Bamako, Mali. Our data suggest that
      pemphigus in this area presents a distinctive pattern. Our cases of pemphigus
      were diagnosed on the basis of clinical, histological and direct
      immunofluorescence studies. We estimated the annual incidence in the Bamako
      region to be 0.29 cases per 100,000 inhabitants. There was no endemic focus in
      Mali. The disease was observed mainly in women (24 of 30; 80%), especially those
      older than 40 years (mean age, 46.7 years), and in the Fulani ethnic group (10 of
      30; 33%). Our study group was composed of 25 cases of pemphigus foliaceus (PF)
      (83%), four cases of pemphigus vulgaris and one case of pemphigus vegetans.
      Pustules with hypopyon were observed in 11 patients (37%). A diffuse verrucous
      change in the skin was noted in four cases of erythrodermic PF. In 16 patients
      with PF, localized verrucous lesions mimicking seborrhoeic keratoses were
      observed when oral corticosteroid treatment was decreased. Histopathological
      examination demonstrated eosinophilic spongiosis in 50% of patients. These data
      suggest that pemphigus in Mali differs from the two main known patterns of the
      disease: the North American/European one, and the Brazilian pattern, with which
      it shares the predominance of superficial forms but otherwise differs in many
      features.

PMID- 8745896
TI  - The occurrence of bacteraemia with skin surgery.
AB  - The need for chemoprophylaxis for bacterial endocarditis is partly dependent on
      the risk of bacteraemia associated with the procedure, which has not been
      adequately defined for skin surgery. The incidence of postoperative bacteraemia
      in 149 immunocompetent out-patients with non-infected lesions was 0.7% (95% CI
      0.3-3.8%). Procedures included excisions, flaps, grafts and micrographically
      controlled surgery. Coagulase-negative staphylococcus was the most common skin
      isolate at the site of surgery, present in 68.5% of patients. The most effective
      chemoprophylaxis would be intravenous vancomycin, which is inconvenient and has
      an inherent risk of morbidity. Given the low incidence of bacteraemia and the
      disadvantages of the optimum chemoprophylaxis, surgery on non-infected lesions
      does not warrant prophylactic antibiotics to prevent the very low risk of
      bacterial endocarditis.

PMID- 8745897
TI  - Lupus erythematosus profundus: a cutaneous marker for a distinct clinical subset?
AB  - Sixteen patients with histologically confirmed lupus erythematosus profundus were
      followed for a decade (on average). At the initial examination, two of 16 (12%)
      patients fulfilled the 1982 American Rheumatism Association (ARA) criteria for
      systemic lupus erythematosus (SLE). During the period of observation, SLE
      developed in another two (12%) patients, both of whom developed a malar rash. The
      remaining 12 (75%) patients never met the criteria for SLE. Four of the 16 (25%)
      had no extracutaneous manifestation. In conclusion, most patients with lupus
      erythematosus profundus have a relatively mild disease course, although a few
      develop systemic abnormalities and have abnormal laboratory findings.

PMID- 8745898
TI  - Psoriasiform and sclerodermoid dermatitis of the fingers with apparent shortening
      of the nail plate: a distinct entity?
AB  - A Caucasian boy, born to unrelated parents, and with no family history of
      psoriasis or atopy, developed chronic psoriasiform dermatitis on the palmar
      surface of the fingers when he was a year old. At the age of 6, the dorsal
      surface acquired a sclerodermoid appearance and the nail plates appeared to be
      shortened. The disease was unsuccessfully treated topically with emollients,
      keratolytic agents and corticosteroids. At the age of 9, when he was
      hospitalized, finger motility was limited and painful, and movements of the hands
      were impaired. The feet were normal. All the investigations were within normal
      limits. Histology of a biopsy revealed parakeratosis, acanthosis with
      papillomatosis, exocytosis and spongiosis. He was treated with a new oral non
      steroidal anti-inflammatory drug, nimesulide (100 mg/day for 20 days, and then 50
      mg/day for 20 days), and emollients. Marked improvement, and restoration of
      finger motility, were achieved after the first month of treatment; the nail
      plates reappeared because of regression of the eponychium.

PMID- 8745899
TI  - A patient with plaque-stage mycosis fungoides has successfully been treated with
      long-term administration of IFN-gamma and has been in complete remission for more
      than 6 years.
AB  - We report the successful treatment of a patient with plaque-stage mycosis
      fungoides with long-term and intravenous administration of recombinant human
      interferon-gamma (IFN-gamma) and discuss the possible mechanisms of this therapy.
      A 55-year-old female patient had been resistant to existing treatments and had
      suffered repeated exacerbations over a 5-year period. Four weeks after initiation
      of 2 x 10(6) U/day of IFN-gamma, a > 10% decrease in the affected surface area
      was noted. Twenty-two weeks after the administration of 228 x 10(6) U of IFN
      gamma, complete remission (CR) was obtained. The CR continued for 13 weeks, but
      this was followed by an exacerbation. The second CR was obtained after the IFN
      gamma dosage was increased to 16 x 10(6) U/week. The dosage was then gradually
      reduced by 2-4 x 10(6) U every 2 or 3 months. She was treated with a total dose
      of 2814 x 10(6) of IFN-gamma. She has been followed up for more than 6 years, and
      there has been no recurrence of mycotic skin lesions nor any visceral
      involvement. During therapy, no serious side-effects were noted. Long-term
      administration of IFN-gamma is useful for the treatment of patients with
      intractable mycosis fungoides. A gradual decrease in the dose of IFN-gamma is
      important for maintaining remission.

PMID- 8745900
TI  - Graft-versus-host reaction affecting lesional skin but not normal skin in a
      patient with piebaldism.
AB  - A case of graft-vs.-host disease (GVHD) arising solely within an area affected by
      piebaldism is described. The patient, a 35-year-old woman with a single
      hypopigmented patch on the right leg present since birth, had received an
      allogeneic bone marrow transplant (BMT) from an HLA-identical sibling donor, for
      treatment of a myelodysplastic syndrome (MDS). Beginning on day +38 post-BMT, the
      patch developed changes which were histologically consistent with GVHD. Syngeneic
      mixed epidermal cell-lymphocyte reaction (MECLR) testing of tissue from the
      patch, and from adjacent normal skin, showed differences which suggest that
      piebaldism-affected skin is immunologically different from normal skin. These
      findings may offer new insight into the pathophysiology of this disorder.

PMID- 8745901
TI  - Keratosis follicularis spinulosa decalvans: report of a new pedigree.
AB  - Keratosis follicularis spinulosa decalvans is a rare, X-linked genodermatosis
      characterized by follicular hyperkeratosis, scarring alopecia of the scalp,
      eyebrows and eyelashes, corneal dystrophy and photophobia. We describe two cases
      from a large family, the first with keratosis follicularis spinulosa decalvans to
      be reported in the U.K.

PMID- 8745902
TI  - Milia-like idiopathic calcinosis cutis: an unusual dermatosis associated with
      Down syndrome.
AB  - We describe two boys affected by Down syndrome (DS), who showed milia-like
      idiopathic calcinosis cutis (MICC). The clinical diagnosis was confirmed by
      histological examination. All reported cases are reviewed and compared. Syringeal
      structures play a significant part in the pathogenesis of this dermatosis. MICC
      appears to be a poorly recognized condition which, rarely, is associated with DS.

PMID- 8745903
TI  - Epidermolysis bullosa acquisita: report of a case with comparison of immunogold
      electron microscopy using pre- and postembedding labelling.
AB  - A patient with epidermolysis bullosa acquisita (EBA), who has been diagnosed as
      having bullous pemphigoid for 7 years, is reported. By immunoblotting, both the
      latest serum and a 4-year-stored serum sample of the patient, were shown to react
      with the 290-kDa EBA antigen or type VII collagen, but not with bullous
      pemphigoid antigens. Pre-embedding immunogold electron microscopy demonstrated
      that the serum bound to the 'anchoring plaque' and to both ends of the anchoring
      fibrils in the fashion reported previously. In contrast, postembedding
      immunoelectron microscopy showed binding mainly to the lamina densa. These
      results indicate that EBA antigens are localized mainly at the lamina densa.
      Further studies are necessary for confirmation.

PMID- 8745905
TI  - Fixed drug eruption due to ciprofloxacin.
AB  - We describe seven patients with fixed drug eruption (FDE) due to ciprofloxacin,
      five confirmed by rechallenge. These cases make up 8.75% of all cases of FDE seen
      by us during 1992-93. Isolated, and striking involvement of the lips was seen in
      two patients. To our knowledge, only a single case of FDE to ciprofloxacin
      previously has been reported. Our experience suggests that, with widespread use,
      ciprofloxacin could become one of the common drugs causing FDE.

PMID- 8745904
TI  - A case of generalized pustular psoriasis followed by bullous disease: an atypical
      case of bullous pemphigoid or a novel bullous disease?
AB  - We describe a 31-year-old Japanese woman with generalized pustular psoriasis
      treated with PUVA who subsequently developed a bullous disease. Throughout the
      disease course, there was no phase of psoriasis vulgaris. Although several
      reports describe coexistence of psoriasis vulgaris and bullous disease such as
      bullous periphigoid, coexistence of generalized pustular psoriasis without any
      phase of psoriasis vulgaris and bullous disease is rare. As for the bullous
      disease, direct immunofluorescence study showed IgG and C3 deposition along the
      basement membrane zone. Indirect immunofluorescence disclosed IgG antibasement
      membrane zone antibodies. Indirect immunofluorescence on 1 mol/l sodium chloride
      split skin demonstrated linear IgG staining almost exclusively on the dermal side
      of the split. Western immunoblot analysis revealed that the antibody was directed
      to neither epidermolysis bullosa acquisita antigen nor bullous pemphigoid
      antigens. Considering the unusual clinical course, we suspect the possibility of
      a novel autoimmune blistering disease.

PMID- 8745906
TI  - Cutaneous Pneumocystis carinii and Cryptococcus neoformans in AIDS.
AB  - A patient with AIDS was found to have skin lesions which contained the organisms
      Pneumocystis carinii and Cryptococcus neoformans. Both organisms were identified
      using haematoxylin and eosin, Gomori methenamine silver, Giemsa and mucicarmine
      stains. Electron microscopy was performed and confirmed their presence. The
      clinical presentation, histopathology, differential diagnosis and treatment of
      cutaneous P. carinii and C. neoformans in AIDS is presented.

PMID- 8745907
TI  - Leishmania infection occurring in herpes zoster lesions in an HIV-positive
      patient.
AB  - We report the first case of co-infection with herpes zoster and leishmania in the
      same lesion, on the face of a 29-year-old female, who was an intravenous drug
      user and who was HIV positive. The infection was initially resistant to acyclovir
      and itraconazole, and the patient died due to severe internal complications, not
      attributed to visceral leishmaniasis. The prevalence of leishmania infection in
      the Mediterranean countries is increasing among the HIV-positive population
      because of the existence of human carriers. Paradoxically, most of these patients
      show mild forms of visceral leishmaniasis.

PMID- 8745908
TI  - Photolocalized eruption associated with acute hepatitis B virus infection.
AB  - We describe a 24-year-old woman with acute hepatitis B virus infection who
      developed extensive erythematous papules in a photolocalized distribution. The
      eruption occurred during the prodromal phase, and subsided with the development
      of jaundice. She had had moderate sunburn 18 days prior to the development of the
      eruption, which was accentuated on the tanned area. To our knowledge, this is the
      first case of a photolocalized eruption due to hepatitis B virus infection.

PMID- 8745909
TI  - Epstein-Barr virus-related primary cutaneous amyloidosis. Successful treatment
      with acyclovir and interferon-alpha.
AB  - Cutaneous lesions related to chronic active Epstein-Barr virus (EBV) infection
      have been rarely documented in immunocompetent patients. A 30-year-old woman,
      fulfilling the diagnostic criteria for the chronic fatigue syndrome, had a 10
      year history of pruritic brownish macules and papules on her chest and back. Her
      EBV serology was abnormal; the EBV genome was present in the epidermis of
      lesions, in oral secretions, and in peripheral mononuclear cells (PMC). Her blood
      lymphocytes spontaneously outgrew in culture. Histology revealed deposits of
      amyloid in the papillary dermis. Treatment with acyclovir and interferon-alpha
      rapidly improved her condition, stopped the lymphocyte outgrowth in culture, and
      reduced the EBV DNA content in oral secretions and in PMC. These data support an
      endogenous reactivation of EBV infection and suggest a causal relationship with
      primary amyloidosis.

PMID- 8745910
TI  - Proximal subungual onychomycosis due to Microsporum canis.
AB  - A case of proximal subungual onychomycosis due to Microsporum canis in a 36-year
      old woman is presented. The onychomycosis involved the left thumb and the little
      fingernails, with thinning of the nail plate and crumbling of the nail plate
      surface. A milky-white discoloration of the proximal portion of the left
      thumbnail was also evident. A 2-mm longitudinal nail biopsy showed a large number
      of fungal elements in the whole length of the nail plate. Fungal hyphae were more
      numerous in the ventral nail plate and produced detachment of the superficial
      nail plate. The nail bed was not invaded by fungal elements and was devoid of
      inflammatory changes. Proximal subungual onychomycosis is uncommon in
      immunocompetent individuals but has frequently been described in patients with
      AIDS. In our patient, in whom the proximal subungual onychomycosis was due to M.
      canis, there were no clinical or biochemical signs of immunodeficiency. Oral
      treatment with terbinafine, 250 mg/daily for 2 months, produced clinical and
      mycological cure.

PMID- 8745911
TI  - Staging of Sezary syndrome with somatostatin receptor scintigraphy.

PMID- 8745912
TI  - Purpura pigmentosa chronica successfully treated with oral cyclosporin A.

PMID- 8745913
TI  - Characterization of the nail matrix basement membrane zone: an
      immunohistochemical study of normal nails and of the nails in Herlitz junctional
      epidemolysis bullosa.

PMID- 8745914
TI  - True delayed pressure urticaria induced by human Monotard insulin.

PMID- 8745915
TI  - Keratin clumping in epidermolysis bullosa, Dowling-Meara type.

PMID- 8745916
TI  - A case of systemic lupus erythematosus showing acute gangrenous change of
      fingertips.

PMID- 8745917
TI  - A comparative study of human epidermal Langerhans cell densities in 10 anatomical
      sites in healthy and diseased skin.

PMID- 8745918
TI  - Toxic epidermal necrolysis induced by terbinafine in a patient on long-term anti
      epileptics.

PMID- 8745919
TI  - Angiolymphoid hyperplasia with eosinophilia: successful treatment with
      indomethacin farnesil.

PMID- 8745920
TI  - Malignant pleomorphic parotid adenoma with inflammatory cutaneous metastasis.

PMID- 8745921
TI  - The EUROLEISH network: an exercise in partnership.
AB  - The EUROLEISH network arose in 1989 as a spontaneous initiative from contract
      holders funded by the health component of the Science and Technology for
      Development programme of the European Commission (EC). Leishmaniasis projects
      from other programmes (International Scientific Co-operation and Avicenna) joined
      the network later on. The network has three central objectives: to improve
      interactions between laboratory and field scientists; to rank the queries raised
      by health services in order of importance for research; and to develop
      partnerships between European countries and between these and developing
      countries. The EUROLEISH network is run consensually by the contract-holders and
      meets yearly, the subject of each meeting alternating between biology (in Europe)
      and epidemiology (in an endemic country). Presently, the network comprises 66
      contract-holders from 18 projects in 28 countries, with a research budget of 4.6
      million ecus during the Third EC Framework Programme (1990-1994). The next main
      issue to be addressed by the network will probably be the strengthening of
      thematic research, by promoting 'bridge building' between projects at regional
      level.

PMID- 8745922
TI  - Identification of genes mediating lipophosphoglycan biosynthesis by functional
      complementation of Leishmania donovani mutants.
AB  - A powerful approach for identifying the genes involved in the infectious cycle of
      pathogens is functional genetic complementation. Here, the current status of this
      technology in Leishmania is reviewed, focusing on the genes involved in the
      biosynthesis of the unique parasite surface glycolipid, lipophosphoglycan (LPG).
      LPG plays multiple roles in the Leishmania infectious cycle, in both the sand fly
      vector and in establishing successful intracellular parasitism within the
      vertebrate macrophage. The emerging methods for generating LPG mutations and for
      recovering the affected gene(s) by complementation with an episomal genomic
      Leishmania DNA library are reviewed. The properties and probable roles of the
      first two genes identified by this methodology are discussed. These methods also
      show great promise in the search for genes affecting other virulence factors of
      Leishmania as well as in the identification of new drug-resistance loci.

PMID- 8745923
TI  - Parasite-host relationships: in-situ study of Leishmania spp. in resistant and
      susceptible mice.
AB  - The host's skin is a critical tissue in the natural life cycle of the Leishmania
      spp. known to cause an 'asymptomatic' infectious process or cutaneous or visceral
      leishmaniasis in mammals. The dermis, once disturbed by the inoculation of
      infective parasites, becomes a site of dynamic events, the progression of which
      depends upon both host and parasite characteristics. Whatever the final site of
      the morbidity caused by the parasites, whether it be cutaneous, visceral or muco
      cutanous, this site reflects the parasite and host's ability to create a pro- or
      anti-parasite micro-environment. The characteristics of this environment are now
      amenable to analysis in situ, as illustrated by the study of the cutaneous
      processes initiated by inoculation of Leishmania major in laboratory mice.

PMID- 8745924
TI  - The rational design of trypanocidal drugs: selective inhibition of the
      glyceraldehyde-3-phosphate dehydrogenase in Trypanosomatidae.
AB  - Within the framework of a project aimed at the structure-based design of drugs
      for use against sleeping sickness, selective inhibitors were designed,
      synthesised and tested. The target protein was glycosomal glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) and the adenosine part of the NAD cofactor was
      chosen as lead. After one design cycle and exploiting the selectivity cleft in
      trypanosomal GAPDH near the C2 of the adenosine ribose, a selective inhibitor, 2'
      deoxy-2'-(3-methoxybenzamido)adenosine, was obtained. This compound inhibits
      human GAPDH only marginally, whereas the enzymes from Trypanosoma brucei and
      Leishmania mexicana are inhibited by 50% at 2.2 and 0.3 mM, respectively.
      Moreover, the inhibition of the parasite enzyme is 45-fold (T. brucei) or 170
      fold (L. mexicana) greater with this substituted analogue than that produced with
      adenosine.

PMID- 8745925
TI  - Molecular techniques in the characterization of Leishmania isolates from Central
      America.
AB  - The public-health problems caused by leishmaniasis in most countries in Central
      America are becoming more severe. This is partly because of the increasing size
      of the human populations that are at risk and their migratory patterns. Annual
      incidence of the disease in Costa Rica, Honduras, Guatemala, Panama and Nicaragua
      is estimated to be as high as 20,000 cases. Regional changes in the epidemiology
      of the various Leishmania spp. present have emphasized the need for innovative,
      sensitive and accurate diagnostic tools. PCR and isoenzyme, monoclonal antibody,
      schizodeme, DNA-probe and random-amplified, polymorphic DNA analyses have been
      tested. Preliminary indications that Leishmania chagasi was present in Costa Rica
      and Honduras and that interspecific hybrids occurred in Nicaragua have been
      confirmed using these methods. The distribution of the mexicana complex was also
      found to be broader and more heterogeneous than initially expected. Overall,
      there was 87% concordance between the results produced using the different
      techniques.

PMID- 8745926
TI  - New developments in the chemotherapy of leishmaniasis.
AB  - Several significant advances in the chemotherapy of leishmaniasis have occurred
      in the last 10 years. Some of these advances have arisen due to the greater
      awareness of the pharmacokinetic properties of drugs, such as the pentavalent
      antimonials, while others have resulted from the introduction of drugs new to the
      treatment of leishmaniasis, such as aminosidine which can be used both
      systemically and topically against cutaneous leishmaniasis. The most encouraging
      advance is the use of lipid-associated amphotericin B; very short treatments with
      these preparations have been shown to be effective. Other studies have shown the
      usefulness of combination therapy and the use of immune modulators. A number of
      biochemical pathways in Leishmania, such as those associated with purine and
      sterol metabolism, are known to be distinct from those of the mammalian hosts.
      These have been exploited in the search for the rational choice of anti
      leishmanial agents.

PMID- 8745927
TI  - From population to genome: ecogenetics of Leishmania (Viannia) braziliensis and
      L. (V.) peruviana.
AB  - The size polymorphism of nine chromosomes, recognized by specific probes, was
      analysed in populations of Leishmania (Viannia) braziliensis and L. (V.)
      peruviana from various Peruvian biogeographical units. Interpretation of the
      polymorphism, by statistical and phenetic methods, led to the identification of
      five consensus (alpha- and beta-tubulin) and four variable chromosomes. The
      dynamics of the variable chromosomes were studied. The promoter role of the
      environment on their polymorphism was indicated by: (1) the discrimination of L.
      braziliensis (forest) and L. peruviana (Andes) by the size of the chromosome
      containing the gp63 genes; and (2) the fact that, within L. peruviana, the
      polymorphism of the variable chromosomes revealed a strong eco-geographical
      structuring of parasite populations, accompanied by increasing chromosomal
      dissimilarity along a cline from north to south. The adaptative significance of
      the polymorphism of the variable chromosomes was suggested by: (1) a correlation
      between chromosomal polymorphism and phenotype variability (lesion type in
      patients and virulence in vitro); and (2) the association between the decrease in
      size of the gp63-containing chromosome from L. braziliensis to L. peruviana, and
      a rearrangement of the gp63 genes, probably accompanied by a decrease in their
      copy number. As chromosomal variation was shown to be more dependant on eco
      geographical differences than isoenzymatic variation, chromosome variation and
      enzyme variation probably differ in adaptative significance.

PMID- 8745928
TI  - Experimental models for leishmaniasis and for testing anti-leishmanial vaccines.
AB  - In public health terms, leishmaniases are diseases of humans and dogs, whereas,
      in epidemiological terms, Leishmania spp. are considered to represent infections
      of a wide variety of animals, which represent the natural reservoirs of the
      various parasite species involved. Humans and dogs (which may be considered
      secondary or 'accidental' hosts in the leishmanial life-cycle) often exhibit
      severe clinical signs and symptoms when infected, whereas reservoir hosts
      generally show a few, minor or no signs. This situation makes the definition of a
      suitable laboratory model a difficult one, since the various experimental hosts
      may behave either like a reservoir or an accidental host. This review discusses
      the concept of animal models for leishmaniases and provides a critical evaluation
      of the most common experimental models and their respective advantages and
      disadvantages. In this state-of-the-art review, particular emphasis is given to
      the value of using mouse, hamster, cotton-rat, dog and primate models, especially
      in the context of testing potential anti-leishmanial vaccines.

PMID- 8745929
TI  - Strategies for immune intervention in visceral leishmaniasis.
AB  - Therapeutic intervention remains a major tool for control of visceral
      leishmaniasis (VL). Studies in murine models of VL have demonstrated the efficacy
      of various cytokines, either alone or in conjunction with antimony chemotherapy.
      Here, some basic aspects of the models used to study VL are summarized and the
      recent data in this field are reviewed. Finally, alternative strategies to
      harnessing the protective potential of the host immune response, based on
      augmenting communication between antigen-presenting cells and T cells, are
      discussed.

PMID- 8745930
TI  - Vaccines against leishmaniasis.
AB  - Unlike some other parasites, Leishmania can be grown in cell-free media with
      ease. This simple cultivation and the use of killed parasites as skin-test
      antigens (leishmanin) for diagnosis in humans during the past several decades
      have prompted scientists to try using the killed parasites, with or without
      adjuvant, as vaccines or for immunotherapy. In addition, different recombinant
      molecules, either parasite fractions or genetically engineered organisms (i.e.
      Leishmania made avirulent by removing specific genes, or bacteria carrying and
      expressing leishmanial genes), are being investigated as potential future
      vaccines against leishmaniasis. The 'first-generation' vaccines, composed of
      killed parasites with or without adjuvant, have been derived using an empirical
      approach. The 'second-generation' vaccines have been genetically constructed,
      using a more rational approach. At present, the first-generation vaccines are at
      various stages of Phase I (safety), II (reactivity) or III (efficacy) trials in
      humans. Results are expected in 1-2 years. The second-generation vaccines are,
      however, only in a preclinical state and are not expected to reach clinical
      trials for at least 3 years. The Special Programme for Research and Training in
      Tropical Diseases (TDR) is actively involved in most clinical trials of the first
      generation vaccines and supports many of the second-generation candidates. In the
      present article, the advantages and disadvantages of each approach to vaccine
      development are discussed and the progress being made is briefly reviewed.

PMID- 8745931
TI  - Epidemiology, diagnosis and control of leishmaniasis in the Mediterranean region.
AB  - The leishmaniases are a widespread and medically important group of parasitic
      diseases, some of which pose a serious health threat in communities throughout
      the Mediterranean basin. In 1993, a joint, collaborative study of the
      Mediterranean leishmaniases was initiated by scientists from Israel, Turkey,
      Portugal and the Netherlands. The aim of this project was the development of a
      multi-component approach to the successful control of all forms of leishmaniasis,
      with special emphasis on the more severe, visceral leishmaniasis (VL). The need
      for highly sensitive and accurate new tools to facilitate diagnosis and
      epidemiological surveys of endemic areas and for studies on the immunology of VL
      in laboratory models (dogs and mice) was soon recognized. It is anticipated that
      the development of these tools and the associated technology will provide a
      better understanding of the disease and improve its control.

PMID- 8745932
TI  - DNA-based methods in the detection of Leishmania parasites: field applications
      and practicalities.
AB  - As conventional methods for the detection and/or diagnosis of infections with
      Leishmania parasites have limitations, the DNA-based alternatives have received
      much attention. By targeting multi-copy sequences such as kinetoplast DNA,
      ribosomal RNA genes, mini-exon-derived RNA genes or genomic repeats, the
      sensitivity of these systems can be increased. Similarly, by targeting conserved
      or variable regions of these targets, the specificity can be tailored to the
      genus, complex, species or even the individual isolate level. There are two main
      approaches to DNA-based detection: DNA probes involving hybridization; and
      amplification approaches such as PCR. DNA probes are less sensitive than
      amplification but are useful for large-scale screening of sandfly vectors or
      reservoir hosts, for example. PCR is much more sensitive and has been used for
      patient diagnosis with a sensitivity greater than microscopy or culture. The
      application of DNA probes and PCR can be simplified using chemiluminescent or
      colorimetric end-points, respectively, but both techniques require some
      specialized equipment and a certain degree of technical expertise. For this
      reason, their use is limited to research laboratories or central diagnostic
      facilities.

PMID- 8745933
TI  - Medical information: from Surgeon General to superhighway.
AB  - Few of those engaged in teaching or research can still be unaware of the
      existence of the Internet, a global network which has been created by the
      interconnection of computers in universities, research bodies, commercial
      organizations, and government departments from all over the World. This network
      of networks has become know as the 'information superhighway'; it is growing
      exponentially, acquiring new users by the minute, and expanding, in unexpected
      and exciting ways, the speed of dissemination, and the format and presentation,
      of scientific information. This article attempts to put this burgeoning growth in
      a historical context, and seeks to identify some starting points for
      Internet/World Wide Web exploration for medical and scientific researchers who
      wish to harness this uniquely important instrument for their own purposes.

PMID- 8745934
TI  - Detection of anti-Plasmodium falciparum antibodies directed against a repetitive
      peptide of the gametocyte antigen Pfs2400 in malaria patients in Brazil.
AB  - Sera collected from 164 individuals who had clinical Plasmodium falciparum
      malaria and came from several areas of Brazil where malaria is endemic were
      tested for the presence of anti-gametocyte antibodies. Antibodies directed
      against P. falciparum gametocytes were detected, by IFAT, in the sera of 67.1% of
      these patients. The prevalence of these antibodies was significantly higher in
      patients who had undergone multiple attacks of malaria than in those who were
      experiencing their first attack at the time of serum collection. Although
      circulating gametocytes were detected in 22% of the patients at this time, there
      was no difference in the percentages of IFAT positivity between apparent
      gametocyte 'carriers' and 'non-carriers'. All sera were also tested by ELISA,
      using a dimer of the nonamer peptide [PEE(L/V)VEEV(I/V)]2, which represents a
      tandem consensus repeat of the P. falciparum gametocyte antigen, Pfs2400, a
      target of transmission-blocking antibodies. ELISA demonstrated that 32.9% of the
      patients had antibodies that reacted with this peptide. Positive ELISA reactions
      were significantly more frequent amongst the sera of patients who had had
      multiple malaria attacks than in those undergoing their first malaria episode;
      positivity was lower in the gametocyte 'carriers' than in their 'non-carriers'.
      These results demonstrate that anti-gametocyte antibodies, which have already
      been shown to have potential transmission-blocking activity, are naturally
      elicited in Brazilian patients, the highest rates of seropositivity occurring
      after multiple malaria attacks.

PMID- 8745935
TI  - Asymptomatic malaria parasitaemia and seroreactivities to Plasmodium falciparum
      antigens in blood donors from Ibadan, south-western Nigeria.
AB  - Malaria parasite rates, parasite densities and seroreactivities to two Plasmodium
      falciparum antigens (Pf155/RESA and circumsporozoite protein) were investigated
      in a random sample of 416 blood donors attending the Blood Transfusion Unit of
      the University College Hospital in Ibadan, south-western Nigeria: 224 in October
      November 1991 and 192 in March 1992. The incidence of malaria parasitaeia
      observed in 1991 was significantly higher than that seen in 1992 (41% v. 19%; P <
      0.001). In contrast, the geometric mean parasite density in 1992 was
      significantly higher than in 1991 (440 v. 191) parasites/microliters blood; P <
      0.001). Although parasite rates were highest in the group aged 25-31 years in
      both surveys, there was no apparent correlation between age of donor and parasite
      density in either survey. Parasite density was significantly higher in AA- than
      in AS-haemoglobin individuals only in the 1992 survey (P = 0.050). All the blood
      donors were seropositive for antibodies to crude parasite antigens, indicating
      heavy exposure to malaria infection. Seroreactivity to Pf155/RESA was similar in
      the two surveys but that to circumsporozoite protein (CSP) was significantly
      higher in 1991 than in 1992 (P < 0.001). The seropositivity rates were generally
      similar to malaria-positive and -negative blood donors. In 1992, however, all the
      blood donors with high reactivities to Pf155/RESA, as detected by erythrocyte
      membrane immunofluorscence, were negative for malaria parasites, indicating that
      this group was relatively protected against malaria parasitaemia. It is
      recommended that blood samples from prospective blood donors be examined for
      malaria parasites and that recipients of malaria-infected blood samples be given
      a curative regimen of antimalarials.

PMID- 8745936
TI  - Production and characterization of a monoclonal antibody specific for Trypanosoma
      simiae.
AB  - Monoclonal antibodies (MoAb) were produced against invariant antigens of vector
      forms of Trypanosoma simiae. X63/AG8.653, NSI/1AG401 and Sp20Ag14 myeloma cells
      were fused with splenic lymphocytes from BALB/c mice that had been immunized with
      various preparations of T. simiae procyclics. A T. simiae-specific MoAb
      [KNS7/14.X (IgG1)] was detected in the hybridoma culture supernatants, which were
      screened for antibody activity by micro-plate and dot ELISA. Immunofluorescence
      studies showed that KNS7/14.X stained cytoplasmic antigens in T. simiae
      procyclics. Proteinase-K digestion and periodate oxidation studies revealed that
      KNS7/14.X binds to a carbohydrate antigenic determinant in glycoprotein or
      glycolipid. Cross-reactivity studies using vector forms of T. brucei, T. vivax,
      T. congolense, T. simiae and T. grayi showed that KNS7/14.X only reacted with T.
      simiae. Attempts to generate other T. simiae-specific MoAb, using 107-, 75- or
      41.7-43.6-kDa peptides selected by western blotting analysis, did not yield
      positive results.

PMID- 8745937
TI  - Prevalence of hydatid cysts in livestock from five regions of Jordan.
AB  - When the prevalences of cystic echinococcosis in indigenous sheep, goats, cattle
      and camels from five regions of Jordan were investigated, from March to December
      1992, they were found to be 12.9%, 12.7%, 0.9% and 11%, respectively. They were
      substantially higher in sheep from Karak (27.6%) and in cattle from central
      Jordan (18.0% in Amman and 14.3% in Sahab) than in the same animals in other
      regions. Age-intensity data indicated that the parasite population is endemic in
      sheep and cattle and hyperendemic in goats. Infection rate increased steadily
      with age in sheep, but became constant in goats and cattle when they were about 2
      years of age. The most common locations of cysts were the liver in sheep and
      goats and the lungs in cattle. Co-infection of the liver and lungs was common in
      sheep and cattle. Although the majority of the sheep, cattle and goats had 1-10
      cysts, 20.4% of the sheep and 22.2% of the cattle had 11-50 and 11-30 cysts,
      respectively. Although 38.1% of the cysts in sheep were fertile, only 8.7% of the
      cattle cysts and 4.5% of the goat cysts were in this condition. The overall mean
      number of protoscolices/sheep cyst was 2.7 x 10(3); although the liver cysts had
      more protoscolices than the lung cysts (3.2 x 10(3) v. 1.9 x 10(3)/cyst), more of
      the lung cysts were viable (71.1% v. 62.3%). Some 0.2% of 13,436 sheep and 6.1%
      of 786 cattle imported live into Jordan were infected with hydatid cysts; 16.3%
      of the sheep cysts (61.4% viable) and 9.6% of the cattle cysts (76.1% viable)
      were fertile.

PMID- 8745938
TI  - Epidemiology and control of schistosomiasis mansoni in communities living on the
      Cuando River floodplain of East Caprivi, Namibia.
AB  - The Cuando River area of eastern Caprivi, Namibia, is highly endemic for
      Schistosoma mansoni whereas S. haematobium transmission, due to the scarcity of
      its intermediate host snail, Bulinus africanus, does not occur. Chemotherapy (6
      monthly blanket treatments with praziquantel) combined with focal mollusciciding
      (monthly application of niclosamide) was used in a project in the area to control
      the disease. Although as many adults and pre-school children as possible were
      tested and treated, the project concentrated largely on school-age children. It
      took 3 years for prevalence to decline from > 80% to 20% because of a lack of
      proper sanitary facilities and piped water supplies and high rates of absenteeism
      and re-infection. However, intensity of infection decreased more rapidly, from an
      arithmetic mean of > 200 to < 5 eggs/g faeces. Hepatomegaly was common among
      school children when the project started but could be seen in only a small
      percentage of them after 3 years of control. Neither the bovine schistosome, S.
      mattheei, nor the lechwe schistosomes, S. margrebowiei and S. leiperi, were
      observed in the excreta of humans living in the area.

PMID- 8745939
TI  - Biological and biochemical comparative studies on Schistosoma mansoni from two
      localities in Egypt where S. haematobium is endemic.
AB  - The changing pattern of Schistosoma mansoni and S. haematobium distribution in
      Egypt is generally attributed to ecological changes caused by the construction of
      the Aswan High Dam. Although S. mansoni was previously restricted to Lower Egypt,
      it is now found at certain foci in Upper Egypt. In areas of Lower Egypt where S.
      mansoni and S. haematobium are sympatric, S. mansoni eggs are shed almost
      exclusively in the stools of patients, whereas in Upper Egypt they are more
      frequently shed in the urine. In spite of this difference, the eggs and adult
      worms obtained from hamsters infected with S. mansoni strains from each of these
      areas proved to be morphologically identical. Protein patterns and isoenzyme
      profiles of male or female adult worms of each of the two isolates, obtained from
      infected hamsters, also proved virtually identical. In hamsters with mixed
      infections of S. mansoni and S. haematobium, some S. mansoni females cross-mated
      with S. haematobium males and they then developed ovaries and laid eggs which
      were typical of S. mansoni and which were excreted from the urinary bladder. In
      Upper Egypt, which is predominantly a S. haematobium area, patients with
      established infections may have a preponderance of S. haematobium males
      associated with S. mansoni females. These females may then migrate to the
      vesicular plexus and deposit S. mansoni eggs in the urinary bladder, to be shed
      subsequently in the urine. The observations appear to be better explained by the
      phenomenon of parthenogenesis than by the production of true genetic hybrids.

PMID- 8745940
TI  - Bancroftian filariasis: analysis of infection and disease in five endemic
      communities of north-eastern Tanzania.
AB  - Clinical and parasitological surveys for bancroftia filariasis were carried out
      in five endemic communities in north-eastern Tanzania, covering a population of
      3086 individuals. High microfilarial (mf) prevalences (17.7%-34.7%) and mf
      geometric mean intensities (251-1122 microfilariae/ml) were observed in the
      communities. The mf prevalence generally increased with age, but often levelled
      out in the older age groups. Larger variability was observed in individual mf
      intensities and no clear association between mf geometric mean intensity and age
      or sex was seen. Hydrocele was the most common clinical manifestation (with a
      prevalence of 30.2%-40.0% in male subjects aged > or = 20 years) followed by leg
      elephantiasis (with a prevalence of 2.0%-6.8% in all subjects aged > or = 20
      years). In four of the five communities, there was no significant difference in
      mf prevalence in males aged > or = 20 years between those with and without
      hydrocele. In all the communities, the mf geomtric mean intensities in
      microfilaraemic males with and without hydrocele were not significantly
      different. The present study therefore did not indicate any association between
      hydrocele in males (the most common type of chronic clinical manifestation seen)
      and presence or absence of microfilaraemia. In contrast, only two (4.4%) of the
      45 subjects with leg elephantiasis were microfilaraemic. In children aged 1-15
      years, mf prevalence was significantly higher among those with microfilaraemic
      mothers (18.0%) than among those with amicrofilaraemic mothers (7.9%). The
      children of microfilaraemic mothers were therefore at 2.3-fold higher risk of
      becoming microfilaraemic than the children of amicrofilaraemic mothers. No
      relationship between the mf prevalence of the children and the mf status of their
      fathers was observed.

PMID- 8745941
TI  - A 16-year follow-up study on bancroftian filariasis in three communities of north
      eastern Tanzania.
AB  - The results of a 16-year, parasitological and clinical, follow-up study on
      bancroftian filariasis in three villages in north-eastern Tanzania are reported
      and analysed with respect to the long-term development of microfilaraemia and
      disease. The study revealed an extraordinary static situation, both at the
      community level and at the individual level. No significant differences were
      observed in any of the three villages, with respect to total or age-specific
      prevalences of microfilaraemia, hydrocele in males aged > or = 20 years or leg
      elephantiasis in all subjects aged > or = 20 years, when the results from 1975
      were compared with those from 1991. Overall, 542 of the subjects (37.2% of the
      total) examined in 1975 were re-identified and re-examined in 1991. Of those
      microfilaraeic in 1975, 81.9% were also microfilaraemic in 1991. Similarly, 81.3%
      of those amicrofilaraemic in 1975 were also amicrofilaraemic in 1991. Thus, most
      subjects had the same microfilarial (mf) status at both surveys. The low mf loss
      rate indicates that re-infection of microfilaraemic individuals commonly takes
      place, and results in repeated sequences of microfilaraemia in the same
      individuals. The rate of gain of microfilaraemia was independent of age, thus
      indicating no age-related change in the examined population's susceptibility to
      develop or sustain microfilaraemia. Individual differences in susceptibility to
      develop mirofilaraemia therefore appear to be innately determined, or to be
      acquired in pre-natal or early post-natal life. Neither the presence of hydrocele
      in 1991, nor the development of new cases of hydrocele over the 16-year period
      were related to the mf status in 1975 or 1991, and no association between
      microfilaraemia and this chronic clinical manifestation was observed. The
      association between leg elephantiasis and mf status could not be analysed because
      of the small sample size.

PMID- 8745942
TI  - Tests for possible effects of selection by domestic pyrethroids for resistance in
      culicine and anopheline mosquitoes in Sichuan and Hubei, China.
AB  - Resistance tests, by conventional methods and by observing the time for
      knockdown, showed no evidence for any build up of resistance to deltamethrin in
      malaria vectors from areas where millions of bednets have been treated with this
      compound annually for up to 7 years. However, a strain of Culex quinquefasciatus
      which had been bred in a factory in which volatile pyrethroids are handled had
      developed unequivocal resistance to deltamethrin. Observation of the time for
      knockdown gave clearer discrimination between resistant and susceptible strains
      than did observation of percentage mortality after a standard exposure time.

PMID- 8745943
TI  - Malaria cytoadherence: binding sites for an anti-adhesive antibody on Plasmodium
      falciparum-infected erythrocytes.

PMID- 8745944
TI  - A recent case of visceral leishmaniasis in Somalia.

PMID- 8745945
TI  - Human cysticercosis: risk factors associated with circulating serum antigens in
      an open community of San Luis Potosi, Mexico.

PMID- 8745946
TI  - Resumption of menstruation in three women with secondary amenorrhoea after
      treatment with ivermectin.

PMID- 8745947
TI  - Haemorrhagic colitis induced by Citrullus colocynthis.

PMID- 8745948
TI  - [New perspectives in the serotoninergic treatment for depression].
AB  - A great deal of data support the view that depression is frequently associated
      with a decrease in central serotonergic neurotransmission. Furthermore, this
      neurobiological alteration very probably contributes to depression because
      treatments known to increase the 'serotonergic tone', such as the chronic
      administration of selective serotonin reuptake inhibitors (SSRIs), have
      antidepressant properties. Extensive studies of the mechanisms of action of SSRIs
      led to the discovery of the key role of somato-dendritic 5-HT1A autoreceptors in
      a negative control of serotonergic neurotransmission. From this finding, a new
      treatment of depression has been attempted which consists of the association of
      an SSRI with an antagonist (non-selective) of these autoreceptors. The potent
      antidepressant action of this association (with a shorter delay of action, even
      in depressed patients previously resistant to 'classical' therapies) should
      promote novel therapeutic strategies consisting of raising the 'serotonergic
      tone' by acting on different (but convergent) molecular targets.

PMID- 8745949
TI  - [Follow-up of antidepressive therapy in psychiatric clinical practice].
AB  - The therapeutic drug monitoring of antidepressant drugs is of interest to adapt
      dosage regimens to reduce the number of non-responder patients, to reduce drug
      side effects and to detect non-compliant patients. A therapeutic range is defined
      for many of these drugs and their linear or non-linear kinetics are important
      parameters in clinical practice to define the posology. Some patients, because of
      when there is drug biotransformation polymorphism, are exposed to drug
      accumulation a deficit in isoenzymes of cytochrome P450. The existence of these
      isoenzymes explains the possibility of non-linear kinetics and drug interactions.

PMID- 8745950
TI  - [Evolution of benefit-risk ratio of antidepressants].
AB  - In recent years there has been a change in the risk-benefit ratio of
      antidepressants characterized by improvement in terms of side effects with second
      generation drugs and efficacy in new indications (anxiety disorders for example).
      However, no significant gain in terms of efficacy in major depressive disorders
      has been obtained. Some aspects of the risk-benefit ratio of antidepressants
      should be better assessed before being optimized: for example, onset of action,
      efficacy and safety of long term treatment, in particular dose and duration of
      treatment, suicidal thoughts and suicide in treated patients, effects of
      antidepressants in bipolar disorders, compliance and economic evaluation. In
      conclusion, the evaluation of risk-benefit ratio associated with antidepressants,
      drugs of proven efficacy in many indications, should take into account the risks
      of not treated depressive disorders (chronicity, social functioning and
      mortality).

PMID- 8745951
TI  - [Criteria for choosing antidepressants].
AB  - Since clinical and biological 'markers' in depressive disorders are missing, the
      antidepressive drug choice today is based on several classifications. The
      chemical classification separates antidepressive drugs according to their
      structure. Their activity mechanism and/or specificity on brain neurotransmittors
      constitute the biochemical classification. Their sedative, median or stimulating
      activity provide the therapeutic classification. Which criteria should be used in
      choosing? The choice depends on clinical and biological data obtained from the
      patient. Chemical classification may be useful at a new molecule synthesis level.
      In the biochemical classification, anticholinergic and antihistaminic activities
      inducing side effects and sedation are taken in account. The therapeutic
      classification is usually used first, especially in case of first cure. An
      antidepressive drug will be prescribed according its initial effects on anxiety
      or holding up, facilitating the wait for its antidepressive action. A better
      definition of samples studied and of study aims, and improvement in knowledge
      about activity mechanisms of antidepressive drugs might provide answers regarding
      treatment choice in depressive disorders.

PMID- 8745952
TI  - [Addictive potential in man: methodological aspects].
AB  - Different methods have been developed in clinical abuse liability testing in man.
      Tolerance, psychic and/or physical dependence must be investigated through
      clinical studies during drug development of a new substance. Adequate methodology
      is needed using double-blind, time-blind evaluations, comparisons of different
      dose levels and duration of treatment for a given drug, abrupt and gradual
      interruption of treatment, appropriate period of observation after treatment
      cessation ... The optimal scale to evaluate properly the symptoms occurring after
      drug discontinuation is still under investigation. These studies will or should
      permit the differentiation of rebound, withdrawal and recurrence. Methods
      developed to study reinforcing effects in post-addicts and healthy subjects are
      self-administration and choice procedures. In addition, the more traditional
      approach has been through assessing self-reported effects in which standardized
      questionnaires are used (Addiction Research Center Inventory or A.R.C.I.; Single
      Dose Questionnaire or S.D.Q.). A third focus of measurement has been
      discrimination studies performed in individuals with histories of drug abuse as
      well as healthy subjects. Abuse-liability testing of a new compound needs a
      multidimensional assessment to optimize the predictivity in defining the relative
      risk.

PMID- 8745953
TI  - [Clinical aspects and evaluation of methadone substitution therapy].
AB  - For a long time, regrettable prejudices have slowed down the expansion of
      methadone treatment. The arrival of AIDS and the need to find new therapies for
      addicts have facilitated a reduction in the misunderstanding concerning
      methadone. Methadone does not induce a narcotic, analgesic, or tranquilizing
      state for dependant addicts, is medically very safe and is not necessarily a life
      long cure. Methadone treatments have become the most efficient means of treating
      addicts who are not able or willing to start short term abstinence programmes or
      go to specialized institutions. An evaluation of methadone treatments at the
      Phoenix Foundation in Geneva has confirmed that these programmes were able to
      reduce heroin use, delinquency, prostitution, risk of AIDS, overdoses or suicides
      and to maintain a good medical and psychosocial stability for the majority of the
      patients.

PMID- 8745954
TI  - [Recommendation of 12 September 1994 regarding the report on serious consequences
      related to biomedical research on drugs and related products. Agence de
      Medicaments, Direction de l'Evaluation, Saint Denis, France].

PMID- 8745955
TI  - [Good practices in pharmacovigilance. Drugs for human use].

PMID- 8745956
TI  - [French pharmacovigilance database system: examples of utilisation].
AB  - The French drug surveillance (pharmacovigilance) system is based on a network of
      31 regional centres which receive adverse drug reaction (ADR) reports from health
      professionals and are drug information centers. Cases are entered into a common
      database, with causality scores. This database contains large amounts of data,
      which may be used for pharmaco-epidemiological studies. As an example, all cases
      in which an antihypertensive drug, suspect or not, was cited were identified. ACE
      inhibitor cough was also explored. RESULTS: Since 1985, > 70,000 case reports
      have been entered into the database. 63 per cent were reported by specialists, 20
      per cent by GPs. 54 per cent came from University Hospitals, 21 per cent from
      private practice. The most numerous age group was 60 to 69. The overall sex ratio
      (F/M) was 1.28, the female preponderance being most marked at < 39 and > 70 years
      of age. 43 per cent took only one drug, 20 per cent two drugs, 13.4 per cent
      three, and 24 per cent > three drugs. The most frequently reported effects
      concerned the skin and appendages (15 per cent), general status and central
      nervous system (9.5 per cent each), platelets, liver, and GI systems (6 per cent
      each). Outcome was favourable in 74 per cent. Dechallenge was positive in 71 per
      cent, rechallence in 6 per cent. 3.4 per cent of the patients died; in 2.2 per
      cent death was related to a reaction. Causality assessment indicated close
      temporal relationship (C2 or C3) in 69 per cent of cases; in 51 per cent of
      cases, no other obvious cause was found. 66 per cent of the reactions were
      labelled when reported. The database could also be used to explore drug
      utilisation: as an example, we studied the age and sex distribution of reports
      containing antihypertensive drugs, irrespective of their possible causal role in
      the reaction. Antihypertensives were mentioned in 14 per cent of the reports. The
      age distribution was skewed towards greater age, with a maximum of 70 years. F/M
      was 1.57, with more M use < 20 and 30-59, whereas F were more common between 20
      29 and 60 years. beta-blockers were more often associated with patients under 70,
      whereas above 70 diuretics and centrally acting antihypertensive drugs were more
      often reported. This could be related to greater use or worse tolerance of these
      drugs. As an example of the exploration of a specific drug-reaction relationship,
      we explored the relationship between the use of ACE inhibitors (ACEI) and cough.
      ACE inhibitors were present in 6 per cent of cases, but in 75 per cent of reports
      of cough. F/M was 1.29 (NS) for all reports concerning ACEI, 1.28 for cough
      unrelated to ACEI, 2.1 for cough with ACEI (P < 0.05). Cough was present in 12
      per cent of all reports concerning ACEI. There was no clear difference between
      ACEI for cough or sex ratio; women cough more with ACEI. This does not seem
      related to greater ACEI use by women or to greater sensitivity of women to cough.
      The reason for this sex difference remains to be explained. There are large
      amounts of essentially underutilized data in drug surveillance databases. How
      they can or should be used remains to be validated.

PMID- 8745957
TI  - [Official systems of pharmacovigilance in France and in Spain. Comparison of
      spontaneous reporting in two regional centers: Pays Basque and Bordeaux].
AB  - This report compares the drug surveillance systems in France and Spain. The
      Spanish causality assessment method is explained. The Spanish and French drug
      surveillance systems are rather similar, but with some variations in the data
      analysis and differences between causality algorithms used. Spontaneous reporting
      in two drug surveillance centres, Aquitaine (Bordeaux, France) and in the Spanish
      Basque Country (SBC) (type of reports, reporting form) is compared. Reports
      received by the two centres during the year 1992 are presented. The SBC Centre
      has received more reports and differences in the source and type of effects were
      observed.

PMID- 8745958
TI  - [Anaphylactoid reactions to an injectable solution of a cremophor-containing
      solution of multivitamins].
AB  - We report four anaphylactoid reactions after intravenous administration of a
      cremophor-containing multivitamin hydrosol (Hydrosol Polyvitamine Roche),
      observed over an 8-month period in a small region of France. The reactions
      occurred immediately following intravenous infusion of either ionic solutions or
      parenteral nutrition mixture containing the multivitamin solution. In three
      cases, erythema and dyspnoea appeared within minutes. The infusion was rapidly
      stopped and corticosteroids were given to two patients. The fourth patient had
      erythema and swelling of the face within 30 min of infusion, and severe
      bronchoconstriction and hypotension within 60 min, before infusion was stopped.
      In-vivo histamine release from mast cell was proved. These reactions are highly
      suggestive of an anaphylactoid mechanism, due to the multivitamin solution, as
      all the other drugs were continued without subsequent reactions. The responsible
      agent is thought to be polyethoxylated castor oil (Cremophor EL), as it is known
      to produce such effects. Medical practitioners should evaluate the risk/benefit
      ratio each time they give this drug.

PMID- 8745959
TI  - [Pharmacokinetics of antibiotics in burn patients].
AB  - The pathophysiology associated with major burns is complex and subject to a state
      of flux (coexistence of pain, infectious diseases, multiple trauma, disturbances
      of metabolism and acid-base status, etc) which could affect the disposition and
      the pharmacokinetic behaviour of drugs. In current clinical practice,
      practitioners often use powerful antimicrobial agents; however, few
      pharmacokinetic studies are available in burns patients (of the order of 30
      studies). Furthermore, the methods used are sometimes questionable. After dealing
      with the ethical and physiological context in which such research is undertaken,
      the authors report a review of the pharmacokinetic studies done during the last
      15 years. Concerning both aminoglycosides and glycopeptides, no therapeutic
      recommendations are available (therapeutic schedules). However, in this case,
      therapeutic monitoring is available and represents a suitable tool to better
      master their use. In the case of beta-lactam antibiotics and quinolones, more
      data are available. Some investigations have shown the possibility of
      translesional diffusion of certain agents in burns (such as gentamicin,
      piperacillin/tazobactam combination, or fosfomycin). This phenomenon could be a
      co-factor of success in treatment. Considering the relatively meager
      pharmacokinetic and pharmacodynamic data available in burns, it is important in
      the future to refine our knowledge of the distribution and metabolism of drugs in
      burns patients in order to better master their use. Finally, ethical and
      methodological considerations need to be taken in account.

PMID- 8745960
TI  - [Acute respiratory distress syndrome after injection of leuprorelin].

PMID- 8745961
TI  - [First case of urticaria due to dacarbazine].

PMID- 8745962
TI  - [Alopecia caused by nimodipine].

PMID- 8745963
TI  - [Acute voluntary poisoning with acebutolol].

PMID- 8745964
TI  - Cholestatic hepatitis: ticlopidine suspected.

PMID- 8745965
TI  - [Severe erythema multiforme during terbinafine therapy].

PMID- 8745966
TI  - [Jean Bimar (1921-1995)].

PMID- 8745967
TI  - [Mivacurium and prolonged curarization].

PMID- 8745968
TI  - [Prolonged curarization with mivacurium and suxamethonium: will molecular biology
      allow a diagnostic and therapeutic approach?].

PMID- 8745969
TI  - [Continuous administration of mivacurium for short procedures. Delayed onset and
      recovery from neuromuscular blockade].
AB  - OBJECTIVE: To assess the delays of onset and spontaneous recovery from
      neuromuscular block produced by mivacurium administered by continuous infusion
      for short procedure requiring a deep relaxation. STUDY DESIGN: Prospective open
      non comparative study. PATIENTS: Twenty-nine class ASA I and II adults undergoing
      a stomatological procedure of short duration were included in the study. METHOD:
      General anaesthesia was obtained with a continuous infusion of propofol,
      supplemented with alfentanil and N2O-O2 mixture. Neuromuscular blockade, assessed
      with electromyography of the adductor pollicis muscle, was obtained with
      mivacurium (150 micrograms.kg-1). After restoration of 5% of neuromuscular
      transmission, mivacurium was administered by continuous infusion in order to
      maintain a blockade between 91 and 99%. RESULTS: The delay for decreasing twitch
      height by 95% was 2.9 +/- 1.0 min. The mean dose for maintenance of blockade was
      10.9 +/- 1.5 micrograms.kg-1.min-1. The delay of spontaneous recovery from
      blockade was 10.2 min, 16.6 min and 21.3 min for obtaining 25, 75 and 95% twitchs
      respectively. The delay for the twitch increase from 25 to 75% was 6.6 min.
      DISCUSSION: Mivacurium in continuous infusion provides rapidly a deep and stable
      neuromuscular blockade followed by a rapid spontaneous restoration of
      neuromuscular transmission in patients with normal pseudocholinesterases.

PMID- 8745970
TI  - [Cocaine contact anesthesia for endonasal surgery. Kinetics and clinical
      tolerance of a concentrated solution].
AB  - OBJECTIVE: To assess the pharmacokinetics and clinical tolerance of a 33% cocaine
      solution administered topically for intranasal surgery. STUDY DESIGN: Clinical
      prospective open trial. PATIENTS AND METHODS: Twelve ASA I patients scheduled for
      intranasal surgery were sedated with midazolam 2 mg and fentanyl 50 micrograms.
      Topical anaesthesia was obtained with aqueous 33% cocaine HCl 360 mg, lidocaine
      HCl 140 mg, adrenaline 0.04 mg and naphazoline 0.4 mg. Venous blood samples were
      taken before cocaine application and 15, 30, 45, 60, 90, 120, 150, 180, 240 min
      later. The plasma was immediately separated and the samples were frozen. The
      concentration of cocaine was measured by HPLC. Potential cardiotoxic and
      neurotoxic effects were clinically monitored. RESULTS: The mean dose of cocaine
      applied was 5.85 +/- 1.3 mg.kg-1 and the dose actually delivered was 4 +/- 1.5
      mg.kg-1. The Cmax was 859 +/- 503 ng.mL-1 after a Tmax to 47 +/- 17 min. The mean
      elimination half-life was 87 +/- 19 min (mean +/- SD). The total clearance and
      the volume of distribution were respectively 4,521 +/- 1,858 mL.min-1 and 568 +/-
      273 L. No clinical evidence of toxicity was found. CONCLUSIONS: This study shows
      that it is possible to perform major intranasal surgery under topical anaesthesia
      with a concentrated solution (33%) of cocaine at a high dose (6 mg.kg-1). These
      results differ completely with data obtained in addicts.

PMID- 8745971
TI  - [Severity scores underestimate the seriousness of acute renal failure after
      emergency surgery].
AB  - OBJECTIVES: The predictive value of APACHE II and SAPS severity scores were
      evaluated in a group of patients with acute renal failure admitted in ICU after
      emergency surgery. The criteria of poor prognosis identified in the 24 hours
      following admission were also evaluated. STUDY DESIGN: Open prospective study.
      PATIENTS AND METHODS: During 22 months, we included every patient admitted in ICU
      after emergency surgery with a serum creatinine concentration > or = 130 mumol.L
      1. Clinical and biological parameters were collected in the first 24 hours
      following admission and the severity scores were calculated. Prediction of
      hospital outcome, based on APACHE II score, was calculated. The standard
      mortality ratio (observed mortality/predicted mortality) was calculated. Accuracy
      of SAPS and APACHE II score was compared using ROC curves and comparison of the
      areas under the curves. RESULTS: Death in ICU occurred in 44% of the patients
      while hospital mortality was 51%. The standard mortality ratio for APACHE II
      score was 1.35. The areas under the curves for SAPS and APACHE II scores were not
      statistically different. The criteria of poor prognosis, identified in the first
      24 hours following admission, were cardiovascular failure, oliguria and sepsis.
      CONCLUSION: Conventional severity scores are inaccurate for prediction of
      mortality in patients with acute renal failure following emergency surgery.

PMID- 8745972
TI  - [Chronic cervico-brachial neuralgia treated by cervical epidural injection of
      corticosteroids. Long-term results].
AB  - OBJECTIVE: To assess long-term results of a single cervical epidural
      corticosteroid injection (CECI) in patients suffering from chronic
      cervicobrachial neuralgia (CCBN). STUDY DESIGN: Open prospective study. PATIENTS:
      A CECI was performed in 29 patients suffering for more than 12 months from a non
      compressive and non-surgical CCBN with permanent pain for at least three months
      non relieved by an adequately conducted medical treatment. METHODS: The cervical
      epidural space was injected (C7-T1, 18 G needle) with an increasing volume
      (maximum 10 mL) of isotonic saline solution to exacerbate patient's
      cervicobrachial pain. The patients then received an equivalent volume of 0.5%
      lidocaine plus triamcinolone acetonide (10 mg.mL-1). The pain decrease was
      estimated on a visual analogic scale (VAS), in comparison to intensity of pain
      rated at 100 mm before CECI. RESULTS: The mean volume injected into the epidural
      space was 6 +/- 2 mL. It increased pain in 26 out of 29 patients. After 3 months,
      a success rate of 83% was obtained, with a pain rate of 12 mm on VAS. Concerning
      mid- and long-term results, pain relief remained stable for at least 24 months
      (mean follow-up: 48 +/- 18 months). Simultaneously, the need for analgesics
      decreased significantly. CONCLUSION: A single CECI in patients suffering from non
      compressive and non-surgical CCBN results in long-lasting pain relief.

PMID- 8745973
TI  - [Sevoflurane].
AB  - Sevoflurane, a methylethylether halogenated solely with fluorine, is
      characterized by a low blood/gas solubility (blood/gas partition coefficient =
      0.65). This feature allows in a more rapid uptake and elimination than with more
      soluble agents. MAC is about 2 vol% in young adults and 2.5 vol% in children of
      more than 6 months of age. It undergoes degradation by soda lime in various
      components. Among them, compound A (an olefin) produces renal toxicity in rats.
      Total sevoflurane metabolism represents about 5% of inhaled dose and produces
      inorganic fluorides. However no renal toxic effects has been reported up to now
      in animals and in patients. The effects on central nervous and cardiovascular
      systems are close to those of isoflurane. It decreases cerebral vascular
      resistances and cerebral oxygen consumption, but does not cause convulsive
      activity. It decreases myocardial contractility, systolic arterial pressure and
      systemic vascular resistances, but heart rate remains basically unchanged up to 1
      MAC. It does not sensitize the myocardium to catecholamines. It depresses
      ventilation in a dose-dependent fashion, this effect being more pronounced than
      that of halothane but less than that of both isoflurane and enflurane. It is not
      irritant for the airways and has some bronchodilatory effect. In adults, recovery
      is more rapid than with isoflurane. In children, sevoflurane seems a promising
      agent owing to its good acceptance for mask induction, as well as its favourable
      haemodynamic profile. However due to its rapid elimination, analgesic drugs
      should be administered early enough to decrease the incidence of postoperative
      pain.

PMID- 8745974
TI  - [Prolonged neuromuscular block after mivacurium injection].
AB  - Mivacurium, a new short acting non depolarizing neuromuscular blocker, is
      metabolized, as suxamethonium, by plasma cholinesterase. Therefore its duration
      of action is increased in patients with reduced plasma cholinesterase activity.
      We report a case of prolonged neuromuscular block after an i.v. bolus of
      mivacurium (0.20 mg.kg-1) in a 69 year-old ASA II woman with an unrecognized
      cholinesterase deficiency undergoing a lumbar sympathectomy for arteriopathy of
      the lower limbs. The duration of the block was 6 h and plasma cholinesterase
      concentrations were very low (540 and 610 UI.L-1), as well as the dibucaine
      number (16%), which suggests an homozygous enzymatic deficiency. Mechanical
      ventilation and sedation were continued until spontaneous return of full
      neuromuscular function.

PMID- 8745975
TI  - [Prolonged neuromuscular block after administration of mivacurium caused by
      plasma psueudocholinesterase deficiency].
AB  - Mivacurium is a new neuromuscular blocking agent with a short acting time of
      about 30 min, due to a fast hydrolysis by pseudocholinesterases. This metabolism
      carries a risk for prolonged neuromuscular block in case of an acquired or
      congenital pseudocholinesterase deficiency. We report the case of a 75-year-old
      woman who experienced a neuromuscular block prolonged for 10 h after a single
      dose of 0.35 mg.kg-1 of mivacurium, because of a major pseudocholinesterase (1800
      UI.L-1, normal value: 5400-13200 UI.L-1). The likely cause was a congenital
      deficiency by a homozygote genetic mutation, as usual causes of an acquired
      deficiency had been eliminated.

PMID- 8745976
TI  - [Prolonged neuromuscular block induced by mivacurium in a patient treated with
      cyclophosphamide].
AB  - A case is reported of prolonged neuromuscular block after mivacurium chloride for
      laparoscopic cholecystectomy, in a 45 years old patient, treated with
      cyclophosphamide for a Wegener's granulomatosis. The neuromuscular function
      monitoring by train-of-four showed a duration of action of 75 min after an
      intubation dose of 0.20 mg.kg-1. Additional bolus of 1 mg, corresponding to 25%
      of usual doses, every 10 or 15 min, were sufficient for maintaining muscle
      relaxation. Spontaneous recovery, without any antagonization, lasted 40 min for a
      TOF ratio (T4/T1) > or = 70%. Recovery index from 25 to 75% were 13 min. Plasma
      butyrilcholinesterases activity were reduced to a level of 50%. With reference to
      literature about succinylcholine, the responsibility of cyclophosphamide is
      likely, and discussed. This observation shows the value of monitoring the
      neuromuscular transmission.

PMID- 8745978
TI  - [Reactive hemophagocytic syndrome: a probably underestimated cause of
      thrombocytopenia in intensive acre patients].
AB  - Thrombocytopenia is a common feature in ICU patients which occurs usually in case
      of infection or septic shock. Its mechanisms, which are often unclear, include
      the haemophagocytic syndrome initially linked with histiocytic proliferation but
      probably also associated with infectious diseases. This syndrome is characterized
      by a phagocytosis of medullar blood cells. Reactive haemophagocytic syndrome can
      probably lead to thrombocytopenia in ICU patients as in this case report of a E.
      Coli infection.

PMID- 8745977
TI  - [Value of the monitoring of curarisation during prolonged mivacurium induced
      neuromuscular block].
AB  - A case of neuromuscular blockade of about 200 min of duration, in a 9-year-old
      boy from mivacurium 0.15 mg.kg-1 is reported. The diagnosis was delayed, after
      onset of the first signs of recovery, due to the lack of monitoring of
      neuromuscular transmission. The neuromuscular blockade was reversed with
      neostigmine 0.04 mg.kg-1. Complete reversal required fifty minutes. The presence
      of an abnormal genetic variant of pseudocholinesterases was demonstrated by the
      measurements of pseudocholinesterase activity and dibucaine number. The
      importance of monitoring of neuromuscular transmission for diagnosis and
      treatment of mivacurium-induced neuromuscular blockade is underlined.

PMID- 8745979
TI  - [Outcome of the use of albumin and colloid plasma substitutes from 1989 to 1993
      in a French University Hospital Center].
AB  - OBJECTIVES: To evaluate the use of plasma substitutes (albumin, gelatins,
      dextrans, starches) from 1989 to 1993 in a 3000-bed University hospital and to
      assess the impact of the 1989 consensus conference of the French speaking Society
      of Intensive Care Medicine on the choice of plasma substitutes for treatment of
      hypovolaemia. STUDY DESIGN: Retrospective study of a case series. METHODS: Data
      on the use of albumin and artificial plasma substitutes were obtained from Blood
      Bank and Pharmacy. RESULTS: Between 1989 and 1993, the total amount of
      administered plasma substitutes decreased by 20%, allowing a saving of 1.7
      million FF. There was a 60% decrease in the use of gelatins and dextrans. The
      starches, introduced in 1991, became in 1993 the most used plasma substitute,
      with 37% of the total. The use of albumin showed only a 32% decrease and was
      still in 1993 the main source of expenditure for plasma substitutes, with 3.8
      million FF and 80% of the total cost. The number of plasmapheresis increased by
      15%, whereas the use of albumin for plasmapheresis, almost constant in absolute
      value, increased from 31% in 1989 to 45% in 1993 of the total expenses. There
      were large differences between the services regarding the use of albumin.
      Intensive care and surgical units represented 70% of the total (plasmapheresis
      excluded). In this group, the overall fall of use was 22%, some units obtaining a
      93% decrease whereas other did not change in spite of constant admission numbers.
      Medical units decreased their albumin use by 53%. CONCLUSION: The decrease in the
      albumin use between 1989 and 1993 was not significant. The impact of the
      consensus conference, if any, was weak. A careful evaluation of the prescriptions
      would be necessary to improve the compliance of clinical practice with
      recommendations by the consensus conference.

PMID- 8745980
TI  - [Diabetes and anesthesia: perioperative management of the diabetic patient].

PMID- 8745981
TI  - [Prolonged mivacurium induced neuromuscular block in 5 patients homozygotic for
      atypical butyrylcholinesterase phenotype].

PMID- 8745982
TI  - [Prolonged curarization with suxamethonium caused by pseudocholinesterase plasma
      deficiency during the immediate postpartum period].

PMID- 8745983
TI  - [Cerebrovascular reactivity to CO2 during general anesthesia measured by
      transcranial Doppler ultrasonography].

PMID- 8745984
TI  - [Outcome of usage protocols on implantable devices].

PMID- 8745985
TI  - [Treacher-Collins syndrome: intubation difficulties].

PMID- 8745986
TI  - [Platelet-rich plasma].

PMID- 8745987
TI  - [Hood: a bubble's story?].

PMID- 8745988
TI  - [Risk factors and primary prevention].

PMID- 8745989
TI  - [Changes in the cardiovascular risk indicators in adolescents between 1980 and
      1991].
AB  - The aim of this study was to evaluate the trends of indicators of cardiovascular
      risk (smoking, physical activity, cholesterol, triglycerides...) in adolescents
      between 14 and 18 years of age. The data was recensed at the Centre of Preventive
      Medicine of Vandoeuvre-les-Nancy which was responsible for periodic Social
      Security health check-ups in 6,974 adolescents in 1980, 1984, 1988 and 1991. The
      analysis of the trends of the indicators of cardiovascular risk took into
      consideration the socio-economic changes of the population recruited during this
      period and the long-term analytical variations of biochemical parameters.
      Globally, between 1980 and 1991, there was a decrease in the percentage of
      smokers (21.8% to 13.5%) which was more marked in boys than in girls, an increase
      in physical activities (46.9% to 57.5%), a linear reduction in serum cholesterol
      (4.65 mmol/l to 4.33 mmol/l in boys, and 4.94 mmol/l to 4.72 mmol/l in girls),
      and no significant changes in serum triglycerides. These results confirm those
      reported by others and are encouraging for cardiovascular disease prevention and
      should be confirmed in adults groups.

PMID- 8745990
TI  - [Identification of subjects at high risk of coronary disease in a working
      population using a prediction model].
AB  - Identification of subjects at high risk of coronary morbidity is of major
      interest in the prevention of cardiovascular disease. This report describes the
      use of a multifactorial prediction model for the identification of high risk
      subjects in a French male population. The PCV-METRA study (Prevention
      Cardiovasculaire en Medecine du Travail) monitors risk factors of cardiovascular
      morbidity in a population of men and women employed in big companies in the Paris
      region. A model adapted from a prediction model conceived by K.M. Anderson et al.
      in the Framingham study was used. The modified model enables an estimation of
      individual coronary risk based on 7 factors: age, total cholesterol, HDL
      cholesterol, systolic blood pressure, smoking, diabetes and presence of left
      ventricular hypertrophy, taking into account the relatively low prevalence of
      coronary heart disease in France. The population comprised 4,131 active men aged
      30 to 65 years. The average risk at 5 years was estimated to be 1.6%. Subjects at
      high risk (over the 80th percentile of the risk distribution curve) usually had
      high blood pressures and cholesterol levels. However, nearly 30% of these
      subjects were neither hypertensive nor hypercholesteraemic. It is important to
      note that 3/4 of these smoked. Moreover, they also had low HDL-cholesterol
      levels. A risk table, derived from the Framingham model, is presented. This table
      allows estimation of individual risk at 5 years in men aged 30 to 65 years. In
      each age group, the comparison of individual risk with the percentiles of risk
      distribution in the PCV-METRA population allows identification of high-risk
      subjects. This study proposes a tool for identifying subjects at high risk of
      coronary morbidity in a French male population. This multifactorial model is
      particularly useful for detecting subjects with several borderline factors none
      of which overstep the usually accepted limits.

PMID- 8745991
TI  - [Evaluation of coronary risk: a new technique of measuring lipoprotein (a)].
AB  - The aim of this study was to assess the reliability of immuno-nephelemetric assay
      (INA) of lipoprotein (Lp(a)) compared with immuno-radiometric (IRMA) and immuno
      enzymologic (ELISA) assays in a coronary (P1) and a non-coronary (P2)
      populations. The serums of 66 coronary subjects (P1) with an average age of 61.5
      +/- 10 years and 137 non-coronary subjects (P2) with an average age of 54 +/- 12
      years were analysed by the 3 techniques. The technical characteristics of the INA
      were: negligeable interference with plasminogen (PLG) (< 1/100) for PLG < 375
      mg/l; excellent repeatability and reproducibility at low, medium and high
      concentrations, respectively 12.3 and 7.5%. 1.2 and 1.2%, 1.3 and 1.1%, low
      dependance on sample conservation (stable 5 days at +4 degrees C), excellent
      practicability (simple and quick automised analysis: 10 min). The linear
      correlations with the concentrations of Lp(a) were: excellent with INA/IRMA P1
      and P2: 0.99; very good with INA/ELISA P1: 0.88 and P2: 0.85; very good between
      IRMA/ELISA P1: 0.91 and P2: 0.87. The average values of Lp(a) were 386 mg/l
      (INA), 339 mg/l (IRMA), 316 mg/l (ELISA) for P1, and 231 mg/l (INA), 212 mg/l
      (IRMA) and 153 mg/l (ELISA) for P2, with a significant difference between P1 and
      P2 with all three techniques: 0.0138 (INA), 0.0207 (IRMA) and 0.0001 (ELISA). The
      authors concluded that measuring Lp(a) by INA is reliable with respect to IRMA
      and ELISA techniques, as accurate, quicker, automatised and cheaper, compensating
      for a lower sensitivity, a calculated risk of a non-specific reaction and the
      necessity of a shorter delay of analysis. The comparative results in two
      populations demonstrate it to be an excellent marker of coronary risk for
      epidemiological studies, independant of other risk factors.

PMID- 8745992
TI  - [Has life expectancy of patients after surgery for aortic valve endocarditis
      improved over the last twelve years?].
AB  - Between 1983 and 1991, 104 patients (average age: 52 +/- 13 years) with aortic
      endocarditis (94 on native and 10 on prosthetic valves), were operated, 81 before
      the end of antibiotic therapy. Blood cultures were negative in 17 patients,
      identified a streptococcus in 49 patients, a staphylococcus in 16 patients, and a
      Gram negative or other organism in 22 patients. The following complications were
      observed before surgery: severe cardiac failure in 67 patients, renal failure in
      24 patients, conduction defects in 13 patients, neurological complications in 13
      patients, systemic or coronary embolism in 12 patients. Aortic valve replacement
      was performed in all patients, associated with mitral valve replacement in 25
      patients and tricuspid valve replacement in 1 patient. Twelve patients died after
      surgery (11/81 of early operations, 1/23 operated later; NS). During a follow up
      of 3.5 +/- 2.8 years, there were 24 late deaths, 12 of non cardiovascular causes.
      Of the 20 variables tested, 3 were related to perioperative and late mortality
      (age, cardiac and renal failure). The 5 year survival (58.1 +/- 5.7%) is
      identical to that of the period 1970-1982 despite a very significant drop in
      perioperative mortality. Some of the causes of late mortality (older age of
      patients, changes in the infecting organisms) provide little hope of improving
      the prognosis in the near future. Others suggest that earlier surgery could
      improve the long term prognosis.

PMID- 8745993
TI  - [Survival after His bundle ablation for supraventricular arrhythmia. A 10-years
      experience in 317 consecutive patients].
AB  - Survival after His bundle ablation for supraventricular arrhythmias was analysed
      over 10 years (May 1982 to December 1992) in 312 consecutive patients (5 were
      lost to follow-up): 54 died (17.3%), 13 of sudden death (24%). The survival rates
      were 94.5% at 1 year (n = 256), 80.1% at 5 years (n = 88), 72.8% at 8 years (n =
      20) and 51% at 10 years (n = 4); patients without apparent heart disease had a
      better prognosis. This series serves as a reference for other techniques of His
      bundle ablation.

PMID- 8745994
TI  - [Cerebral protection by selective cerebral perfusion during surgery on the aortic
      arch].
AB  - The aim of this study was to evaluate the technique of cerebral protection by
      selective cerebral perfusion with moderate hypothermia during surgery of the
      transverse aortic arch. Twenty-three patients were operated for partial or total
      replacement of the transverse aortic arch between January 1987 and December 1993
      by the technique of selective cerebral perfusion by bilateral carotid
      cannulation. There were 12 cases of aneurysm of the ascending aorta and/or
      transverse aortic arch, one aneurysm of the innominate artery and 10 Stanford
      type A aortic dissections. The selective cerebral flow rate was 1-1.5 l/min; the
      perfusion pressure 60-80 mmHg and the temperature of cerebral perfusion 25-28
      degrees C. The perioperative mortality was 13%; the causes of death were not
      neurological (3 haemorrhages). The neurological morbidity was 10% (one brachial
      monoparesis and one bulbar tetraparesis). This is therefore a useful technique of
      cerebral protection which avoids the complications of deep hypothermia with
      circulatory arrest and does not limit the time of aortic repair.

PMID- 8745995
TI  - [Changes in the high-amplification electrocardiogram after myocardial
      revascularization. Comparison between coronary artery bypass and angioplasty].
AB  - The signal-averaged electrocardiogram (SA-ECG) was studied in 148 patients
      undergoing myocardial revascularisation either by coronary bypass surgery (CBS)
      (64 cases) or transluminal angioplasty (PTCA) (84 cases). The investigation was
      performed before the procedure, at day 7 (D7) and after 3 months (D120). No
      difference was observed in the SA-ECG between the two groups before
      revascularisation. The CBS population was older, more symptomatic and had more
      severe lesions than the PTCA population. One hundred and thirty-nine patients
      were followed up until the end of the study protocol (CBS = 63; PTCA = 76). Two
      criteria of the SA-ECG were significantly modified after CBS: QRS duration (p <
      0.05) and Under 40 (p < 0.01). No significant changes were observed after PTCA.
      In the patients with late potentials (LP) before revascularisation, the mean
      value of these criteria (Under 40 and Last 40) were significantly modified after
      CBS (U40 = 54.3 +/- 16 to 35.4 +/- 15; p < 0.01) (L40 = 11.9 +/- 4.7 to 26.1 +/-
      24.3; p < 0.01). No changes in these criteria were observed after PTCA. The value
      of negativation of the criteria of LP for patients with two criteria of
      positivity was 71.1% after CBS compared with 25% after PTCA (not significant).
      These observations support the hypothesis of a favourable modification of the
      arrhythmogenic substrate after myocardial revascularisation, especially by CBS.

PMID- 8745996
TI  - [Influence of the duration of myocardial infarction on QRS duration measured by
      signal averaged electrocardiography].
AB  - The aim of this study was to determine the influence of the chronicity of
      myocardial infarction on QRS duration. The signal-averaged electrocardiogram (SA
      ECG) was recorded with a 40 Hz filter in 239 patients with a history of
      myocardial infarction. The infarction was recent (up to 6 weeks) in 105 patients
      (group A) and chronic (> 1 year) in the other 134 cases (group B). In group A, 35
      patients had inductible sustained ventricular tachycardia (VT) at less than
      270/mn; 40 had negative electrophysiological investigations and 30 had inducible
      ventricular flutter or fibrillation (VF). In group B, 58 had inducible VT, 54 had
      negative investigations and 22 had inducible VF. The three SA ECG parameters (QRS
      duration, amplitude of RMS 40 and duration of LAS) differed significantly in
      subjects with VT with respect to those with negative investigations and inducible
      VF, irrespective of the chronicity of infarction. On the other hand, only QRS
      duration differentiated patients with recent infarction from those with chronic
      infarction, irrespective of the results of programmed pacing, QRS duration being
      longer in group B. The best diagnostic value of QRS duration for identifying
      subjects with VT < 270/mn and negative investigations was 110 ms in group A and
      120 ms in group B (sensitivity 46% and 77.5% respectively). In chronic
      infarction, the increase in QRS duration was significantly correlated to the
      decrease in left ventricular ejection fraction. The authors conclude that the
      criteria of abnormality of QRS duration are dependent on the chronicity of
      myocardial infarction. Although a duration of 110 ms is abnormal in the early
      post-infarction period, after a period of one year, a value of 120 ms should be
      considered to be pathological, especially when the sequellae of infarction are
      important.

PMID- 8745997
TI  - [Changes in heart rate variability after myocardial infarction. Value of
      Poincaree's diagram].
AB  - The variability of the heart rate is reduced after myocardial infarction. It then
      progressively increases, to return to near normal values after several months.
      However, these changes in heart rate variability occur at the same time as
      slowing of the heart rate which makes interpretation difficult. Poincare's
      diagram is constructed from a Holter recording plotting each RR interval against
      the preceding RR interval. The authors have developed a geometric approach to
      this diagram to evaluate parasympathetic tone for a given heart rate. By
      measuring the dispersion in height of the Poincare's diagram, the authors
      evaluate the shor-term variability for a given RR interval. Two 24 hr Holter
      recordings were performed in 52 patients at one and two weeks after a myocardial
      infarction. The dispersion in the height of the Poincare's diagrams was measured
      at the 10th, 25th, 50th, 75th and 90th percentiles of the total dispersion. The
      authors have shown an increase in the short-term variability of the shortest RR
      intervals (1th, 25th and 50th percentiles) which is not observed in the longer RR
      intervals (75th and 90th percentiles). In conclusion, theres is an increase in
      the heart rate variability at the shortest RR intervals. This suggests that the
      recovery of parasympathic tone after myocardial infarction occurs mainly at the
      fastest heart rates.

PMID- 8745998
TI  - [Automatic implantable defibrillator and antiarrhythmic surgery in ischemic
      cardiopathies. Apropos of 53 cases].
AB  - The automatic implantable defibrillator (AID) and antiarrhythmic surgery are the
      two therapeutic options after failure of catheter ablation and/or antiarrhythmic
      therapy for sustained ventricular tachycardia (VT) or ventricular fibrillation
      (VF) in patients with coronary artery disease. The authors undertook
      retrospective study of the characteristics of two groups of patients treated
      between November 31st 1987 et December 31st 1993 either by AID (28 men and 4
      women with an average age of: 56.1 +/- 11.2 years) or by surgery (19 men and 2
      women with an average age of: 60.6 +/- 6.8 years). The "surgical" patients
      differed from "defibrillator" patients in the fewer number of cardiac arrests, a
      higher proportion of sustained monomorphic VT, better tolerated sustained
      monomorphic VT (rarely syncopal), fewer early post-infarction arrythmias (< or =
      8 weeks), more anterior wall infarction and a higher proportion of aneuvrysms.
      The perioperative mortality was 6.2% in the "defibrillator" group and nil in the
      "surgical" group (p = NS). At 2 years, the sudden death rate in the
      "defibrillator" and "surgical" groups was 7.5% and 0% respectively and total
      cardiac mortality was 17% and 20% respectively (p = NS). The authors conclude
      that perioperative mortality and the sudden death rate at 2 years are relatively
      low in the two groups. However, the total cardiac mortality remains high, largely
      related to perioperative death and secondary cardiac failure. Nevertheless,
      compared with defibrillator patients and with identical average ejection
      fractions, there was no extra mortality due to cardiac failure after
      antiarrhythmic surgery.

PMID- 8745999
TI  - [Post-partum cardiomyopathy: medical aspects, role of heart transplantation].
AB  - The incidence of post-partum cardiomyopathies (PPCM) represents 5% of all
      cardiomyopathies and 10-13% of cardiomyopathies in women. The outcome of PPCM may
      be: a) death in the acute phase, b) evolution to chronic myocardial disease or c)
      complete recovery, in which PPCM differs from dilated cardiomyopathy. Another
      difference is that PPCM may not recur in subsequent pregnancies. The aetiology
      and pathogenesis of PPCM are still unknown. Infectious diseases, nutritional
      disorders have been reported but they do not account for the majority of cases.
      Immune responses to the foreign tissue of the placenta and foetus may explain
      alteration of immune function associated with myocardial lesion. In the author's
      experience, the most common pathogenic mechanism is latent myocardial
      insufficiency observed in each woman in the normal post-partum period. The
      different noted "causes" could be factors which reveal this latent common
      condition. Recently, cardiac transplants for PPCM have been reported. As patients
      with PPCM may recover completely, we believe that PPCM is not a special priority
      for transplantation. Two recent studies have compared the outcome of women
      undergoing transplantation for PPCM and those for dilated cardiomyopathy. The
      risk of rejection and infection was greater in PPCM (but the difference was
      significant in only one report). The long-term survival was favourable in both
      groups.

PMID- 8746000
TI  - [Dyslipidemia, lipid lowering drugs and thrombosis].
AB  - Many abnormalities of haemostasis have been described in hyperlipidaemias. They
      are especially marked in hypertriglyceridaemia with raised factor VII, PAI-1 and,
      sometimes, fibrinogen levels. The hypercholesterolaemias are associated with a
      raised haematocrit and blood viscosity. Changes in platelet aggregation are
      inconstant and consist of platelet activation in vivo and increased reactivity ex
      vivo. The origin of these disturbances has not been clearly established. Some,
      like the hyperfibrinogenaemia or platelet activation, are perhaps only secondary
      to the vascular disease caused by the dyslipidaemia. The effect of lipid-lowering
      therapy on these abnormalities varies according to the class of drug. Several
      fibrate-derivatives decrease fibrinogen, factor VII, PAI-1 levels and platelet
      activation. The resins have little effect on the parameters of haemostasis. The
      statins reduce platelet activation in and ex vivo, and, inconsistently, correct
      blood hyperviscosity. It is to early to attribute clinical importance to the
      effects on haemostasis of lipid-lowering drugs. Although it has been demonstrated
      that some statins have a rapid preventive action after only several months'
      treatment, on myocardial infarction and coronary deaths, it is also true that
      resins, which do not affect haemostatic parameters, are also effective in
      preventing coronary events. The most widely accepted mode of action of lipid
      lowering drugs is the stabilisation of atheromatous plaques.

PMID- 8746001
TI  - [Pulmonary hypertension associated with portal hypertension. Apropos of 2 cases].
AB  - The authors report the cases of two patients with pulmonary hypertension
      associated with portal hypertension. This is a rare association with a reported
      prevalence ranging from 0.25 to 0.73%. The diagnosis of portal hypertension
      preceded that of pulmonary hypertension by several years. The physiopathological
      mechanism of the latter is not well known although several hypotheses have been
      proposed. Treatment is only symptomatic. The prognosis is usually poor, the
      causes of death being related to complications of liver failure and/or portal
      hypertension or to those of pulmonary hypertension.

PMID- 8746002
TI  - [Supraventricular tachycardia due to simultaneous conduction in the rapid and
      slow nodal pathways. Treatment by ablation of the slow pathway].
AB  - The authors report the case of a 70 year old woman with frequent attacks of
      supraventricular tachycardia resistant to antiarrhythmic therapy. The tachycardia
      was irregular with predominantly normal QRS complexes. Electrophysiological
      investigation showed dual conduction in the atrioventricular node and tachycardia
      was induced by atrial extrastimulus. However, reentrant tachycardia could not be
      induced, the refractory period of the slow pathway being much longer than that of
      the rapid pathway. The mechanism of the tachycardia was simultaneous conduction
      of the sinus rhythm through the two nodal conduction pathways. This was
      successfully treated by radiofrequency ablation of the slow pathway.

PMID- 8746003
TI  - [Acute pericarditis in Coxiella burnetti infection. Apropos of a case].
AB  - The authors report a case of pleuro-pericarditis during an acute Coxiella
      burnetii infection. They point out the rarity of this mode of presentation of
      acute Q fever and the diagnostic difficulties in the absence of focal pulmonary
      or hepatic signs. The diagnosis was confirmed by serological changes, essentially
      indirect immunofluorescence. They underline the importance of early diagnosis
      before the disease become chronic, exposing the patient to more serious cardiac
      disease which may be difficult to treat.

PMID- 8746004
TI  - [Echo-guided percutaneous cholecystostomy in the treatment of acute
      cholecystitis. Apropos of 41 cases].
AB  - Differents studies note many complications of the traditional cholecystectomy for
      acute cholecystitis in critically ill and very old patients. We report a
      retrospective study of ultrasound-guided cholecystostomy as an alternative
      treatment avoiding surgery in 41 patients between April 1988 and January 1994.
      Mean-age was 77.8 years (42-95). Hospital mortality concerned five (12.2%)
      patients. Four (9.8%) required surgical procedure, all of them with simple post
      operative course. Six (14.6%) had a recurrence between 1 and 67 months after the
      end of the drainage. Twenty-six patients are considered as healed, without
      recurrence, after a mean-follow-up of 33 months. The percutaneous echoguided
      cholecystostomy seems to be a treatment of choice for patients with a
      contraindication for a surgical procedure. This technic allows an efficient
      treatment in patients with post-operative cholecystitis.

PMID- 8746005
TI  - [Lymphadenectomies in the surgery of stomach cancer].
AB  - This paper describes the author's personal experience (363 cases: 1950-1982) in
      gastric cancer surgery, with a lymphadenectomy closely resembling the one
      currently in use. The first results were published in 1970. The final results
      confirm that enlarged lymphadenectomy is beneficial not only in total but also in
      subtotal gastrectomies performed to remove tumours in the lower half of the
      stomach. Lymphonodal invasion influences final outcome.

PMID- 8746006
TI  - [Liver tumors around the vena cava. Strategy for surgical approach of segments I
      and IX].
AB  - The technical problems raised by the delicate surgery of tumours of the liver
      developing around the vena cava, with and without invasion of segments I and IX
      was studied on the basis of 7 cases reports. The intra- or extra-hepatic pedicule
      route, the denudation of the entire retrohepatic vena cava, and the clamping
      needed for exsanguinous surgery are presented together with future perspectives
      including 3-D liver imaging, stimulation of liver regeneration potential and ex
      vivo techniques are discussed with the aim of more and more carcinological liver
      surgery.

PMID- 8746007
TI  - [Multiple free transplants in microsurgery for cervicofacial reconstruction].
AB  - Microsurgical techniques open the way for much creativity and originality for
      cervicofacial reconstruction and tumoral repair. Between 1976 and 1994, we
      performed 481 free transplants for cervico-facial reconstruction. A recently
      developed strategy has been the use of multiple free transplants, either
      simultaneously or successively. Between 1990 and 1994, we operated and
      reconstructed 9 patients using multiple free cervico-cephalic transplants after
      multitissular and agressive exeresis for tumoral or traumatic lesions. In 3
      cases, the transplants were made simultaneously and in the 6 others successively.
      Three patients received 3 free transplants and 6 patients had 2. In 8 cases, each
      of the transplants was micro-anastomosed on different vessels. In one case, the
      two transplants were anastomosed in series, the most distal portion being
      connected to the most proximal portion (in comparison with the cervical vessels).
      One death occurred at 6 weeks due to infectious complications. The final result
      for the 8 other patients was good both morphologically and functionally.
      Indications for multiple free transplants include: complex tissue loss, multiple
      and massive tissue loss of the cervicocephalic region. This situation occurs
      particularly in case of voluminous tumours invading several structures, in
      multiple tumours and in firearm wounds. These series of patients allowed a
      definition of recommended techniques in case of difficulties in these very
      elaborate surgical procedures and confirmed that if the strategy is correctly
      planned, it is possible to greatly improve the quality of survival in these
      patients in terms of aesthetics, morphology and function.

PMID- 8746008
TI  - [Influence of the Strasbourg School of Health (1794) on the creation of the
      Imperial School of the Military Health Service].
AB  - The two-hundredth anniversary of the creation of the School of Health in
      Strasbourg was celebrated on December 3rd, 1994. Early in its history, the School
      also trained officers in the military health service. The close relationship
      between civilians and the military at the School led to the creation of the
      Imperial School of the Military Health Service which opened its doors in
      Strasbourg in 1856. Teaching was unfortunately halted by the war in 1870 and the
      school did not reopen until it was transfered to Lyon in 1888 where the former
      organization of the Imperial School of Strasbourg was maintained. "Si la faculte
      de Strasbourg a emprunte plus d'un de ses professeurs a la medecine militaire,
      combien celle-ci, en meme temps, ne lui a-t-elle pas fourni de disciples?"

PMID- 8746009
TI  - [Evaluation of coronary risk in patients with subrenal abdominal aortic
      aneurysm].
AB  - Atheroma lesions are often found in multiple localizations. In addition,
      operative mortality for aneurysms of the non-ruptured sub-renal aorta is mainly
      related to coronary risk. In an attempt to reduce coronary risk, coronarography
      was performed in all patients (n = 297) from January 1989. Operation for the
      aneurysm was performed in 192 patients (reasons for not operating were small size
      of the aneurysm, other contraindication). There were 5 deaths, all related to
      coronary artery disease. Coronary bypass was performed in 42 patients either
      before (n = 38) or at the same time (n = 4) as the operation for the aneurysm of
      the aorta. There were no operative deaths. These results clearly demonstrate the
      importance of search and treatment of associated coronary lesions in all patients
      with an aneurysm of the subrenal abdominal aorta. Coronary lesions should be
      treated whenever morphology allows.

PMID- 8746010
TI  - [Endoscopic opening of the carpal canal].
AB  - A prospective study of 280 endoscopic operations of the carpal canal using the
      AGEE technique were reported. The first 80 cases were studied separately from the
      200 subsequent cases. In the first series, the only complication was the need for
      an incision in 6 cases because of technical problems or anatomic variants (13%).
      An increase in the degree of paraesthesia was observed in 8% of the cases. In the
      200 subsequent cases, one only required a classical incision and the lubrication
      of the blade was sufficient to reduce the frequency of post-operative aggravation
      of the paraesthesia to 1%. Five percent of the patients complained spontaneously
      of pain in the palm of the hand but a rate of 49% was found after questioning.
      Grip force fell less than after classical opening and recovery was more rapid and
      more complete.

PMID- 8746011
TI  - [Echography of the foot in newborn infants. Preliminary study].
AB  - Xrays are of a poor help in the diagnosis of the deformities of the foot in the
      neonate. As a modern imagying, ultrasounds allow to show the cartilaginous frames
      and also the soft-tissues. Some special views are used which can give interesting
      informations about the abnormal connexions of the hindfoot and also the midtarsal
      joint. This procedure is also used for the follow up during the treatment in
      order to appreciate its efficiency.

PMID- 8746012
TI  - [Solid and papillary tumor of the pancreas].
AB  - A patient who was treated in 1978 by duodenopancreatectomy for a tumour of the
      second duodenum survived for 15 years before death caused by trauma. The
      pathology slides were therefore reassessed and led, a posteriori, to the
      diagnosis of solid papillary tumour of the pancreas according to the new criteria
      described by Kloppel. The 86 references found in the literature reported 139
      cases although many were too vague to be retained. Precise diagnosis can only be
      obtained on the basis of immunohistochemistry and ultra-structure criteria as
      described here.

PMID- 8746013
TI  - [Vascular microanastomosis with diode laser. Control study and morphological
      results].
AB  - Direct diode laser carotid (0.7-1.2 mm) end-to-end microanastomosis versus contro
      lateral manual suture microanastomosis (CMA) were performed in 70 Wistar rats.
      The laser beam-wavelength 830 nm- was transmitted through a micromanipulator and
      provided a focused spot of 300 microns in diameter. After placement of three 10.0
      Ethilon stitches for edge coaptation, the laser anastomosis was performed using
      laser shots (average 3) of 500 mW power, 4.5 s duration and 700 W/cm2 irradiance
      each. CMA was performed by six 10.0 stitches. Good vascular flow was confirmed by
      macroscopic controls, Doppler spectral analysis (n = 548) and digitalized
      angiography (n = 18) performed from day 0 to day 210. The patency rate (93%) as
      well as the complication rate (5/66) were similar in both series. Nevertheless
      light and scanning electron microscopy (n = 82) showed the morphological
      superiority of laser anastomosis: reendothelialization by day 3 and medial
      collagen restructuration by day 10 whilst after CMA, the arterial wall repair was
      delayed and the medial scar occupied by fibrotic tissue. The other advantages of
      the laser anastomosis were, shorter operating time minimizing organ ischemia (13
      min versus 22 min), and slight endothelial trauma reducing thrombogenic risk. The
      technical advantages of diode laser were pointed out: miniaturization, no special
      maintenance and decreasing price of diodes.

PMID- 8746014
TI  - [Lymph node involvement and prognosis in medullary cancers of the thyroid gland].
AB  - Involvement of regional lymph nodes is extremely common in medullary carcinoma of
      the thyroid gland (MTC). The aim of the present study was to determinate the
      prognostic of MTC correlated with the regional lymph node involvement. From 1975
      to 1994, 23 MTC patients were treated. The surgical protocol included a total
      thyroidectomy with bilateral dissection of the jugulocarotid chain and of the
      paratracheal groove. We have distinguished two groups: group N+ (histological
      lymph nodes involvement) and group N- (absence of histological lymph nodes
      involvement). In each group we have evaluated the prognostic significance of age,
      sex, palpable lymph nodes, histological capsular effraction and presence of
      distant metastasis. The data were analyzed with the exact Fisher test and
      comparisons by Student t test. Significance was defined as p > 0.05. Survical
      curves were based on the method of Kaplan Meier. In Group N+ (n = 15), 9/15
      patients died: they had palpable lymph nodes, histological capsular effraction
      and distant synchronous or metachronous metastasis. The median survival was 8
      months, when patients have distant metastasis. Six patients are alive, 2 with an
      elevated thyrocalcitonin level without metastasis, and 3 with resection of
      metastatic MCT to regional lymph nodes. In groupe N- (n = 8), all patients are
      alive: 2/8 patients had palpable lymph nodes, 1/8 had histological capsular
      effraction, but none had distant metastasis. 2 patients underwent resection of
      regional lymph metastasis and one of pulmonary metachronous metastasis. Gender
      did not appear to affect the lymph involvement. Factors significantly associated
      in the group N+ included the following: age (p = 0.003), palpable lymph nodes (p
      = 0.015), capsular effraction (p > 0.00025), distant synchronous metastasis (p <
      0.013). The regional lymph node metastasis had significant influence on the 5
      year survival, 48% vs 100% (p = 0.006), and on disease free survival, 16.6% vs
      62.5% (p = 0.018). The median time from resection of the primary tumor to the
      development of metastasis disease was 37 months for patients N+ vs 169 months for
      patients N-. Involvement lymph node did not affect the metastasis disease,
      regional involvement or distant metastasis (p > 0.05).

PMID- 8746015
TI  - [Is there a reasonable role for prosthetic materials in the emergency treatment
      of hernias?].
AB  - On the basis of 54 reparations par prosthesis among our personal series of 264
      strangled hernias, we tried to define the situations where prosthetic material
      should be used in emergency procedures. Use of a plug for the cure of crural
      hernias was found to be effective and usually a reasonable option. Inversely,
      large prostheses cannot be proposed except in a limited number of cases using an
      indirect approach in order to assure correct separation between the septic
      procedure for intestinal resection and abdominal wall repair.

PMID- 8746016
TI  - [Therapeutic strategy in 46 cases of radiation injury of the intestine].
AB  - Our experience in the treatment of 46 cases with radiation enteritis (RE)
      permitted to summarize 5 key points in the Surgical Strategy: laparotomy
      incision, enterolysis technique, small bowel and colon preservation, anastomosis
      technic and parenteral nutritional support. Surgery is imposed most of the time
      in digestive and nutritional Insufficiencies due to radiation enteritis. 46
      patients aged to 33-81 years (mean age = 59) were included for possible surgery.
      The first clinical digestive symptoms were occlusion (n = 39) and/or digestive
      fistula (n = 7) and/or perforation (n = 3). These abnormalities were often
      associated with severe malnutrition (weight loss > or = 20% of usual weight)
      inducing surgery preparation with pre-operative parenteral nutrition (8 to 350
      days). 3 patients were not operated because of general problems and lived 1 to 7
      months after the beginning of parenteral nutrition. For operated patients (n =
      43), 12 underwent 2 operations (resection and/or enteral liberation) and one
      patient underwent 4 surgical interventions because of digestive fistula. In 35
      cases, small bowel resection was performed leaving 135.4 +/- 62.6 cm of intestine
      (0 to 225 cm of jejunum and/or ileum) and in 13 cases, complete enterolysis was
      achieved. All the patients received a post-operative parenteral nutrition during
      1 to 23 months (median = 6.2 +/- 5.3 months). 31 patients received home
      parenteral nutrition during the pre and/or post-operative phase for a median
      duration of 6.3 +/- 3.2 months (range: 1-23 months). 4 patients died during the
      immediate post-operative phase and among them, 3 died after the second surgery.
      12 deaths were observed due to the primary cancer and 6 due to the evolution of
      radiation lesions. Median survival of patients without cancer evolution reach 180
      months with a 5-year survival rate of 94% (Kaplan-Meier method). In patients with
      radiation enteritis, the pre and post-operative nutritional support associated
      with radical surgery allows to obtain prolonged survival in non cancer patients.

PMID- 8746017
TI  - [Echo-guided percutaneous cholecystostomy in the treatment of acute lithiasic
      cholecystitis. Apropos of the communication of J. Visset and al. Meeting of 1
      February 1995].

PMID- 8746018
TI  - [Cytomegalovirus pneumopathies. What role should be given to cytomegaloviruses
      isolated from blood and bronchoalveolar lavage fluid in AIDS and from organ and
      bone marrow grafts?].
AB  - Cytomegalovirus (CMV) is often suspected as the causal agent in lung disease
      occurring in various immunodepressive states: AIDS, organ transplantation, bone
      marrow graft. The mechanisms involved in these three situations is however quite
      different. The role played by the cytopathogenic effect of the virus and the
      immune reaction of the host vary considerably depending on the underlying
      immunodepression. Thus, the criteria allowing to distinguish between CMV
      infection (presence of the virus or anti-CMV antibodies, no clinical signs) and
      CMV disease (generalized or organ specific disease resulting from the pathogenic
      effect of CMV replication) lack precision. The aim of this review of the
      literature is to assess the implicated immunovirology mechanism and thus the
      diagnostic (and thus therapeutic) criteria of CMV lung diseases. There is a
      graduation scale from AIDS, to organ transplantation and bone marrow allograft in
      the degree of immune reaction implicated in the lung disease and thus the need
      and timing of antiviral treatment. In AIDS, an interstitial pneumonia, associated
      with an isolation of CMV (whatever the sample origin, blood, bronchoalveolar
      lavage or the isolation technique) does not usually implicate treatment.
      Treatment may be indicated in rare cases (advanced stage immunodepression, high
      virus titre, endothelial involvement) or in cases in which the infection is also
      located in other organs. For organ transplantation, observation of CMV in blood
      or lavage samples in a patient with clinical or radiological signs would justify
      treatment. For lung transplantation, more so than for any other organ, treatment
      should be started early whenever respiratory signs are associated with evidence
      of CMV infection. Finally, in bone marrow allografts, the high rate of failure
      when pneumonitis has become patent implicates starting treatment immediately upon
      diagnosis of CMV infection. The strategy proposed here is based on a certain
      rationale but can be open to discussion. Controlled clinical trials are required
      to determine the most rigorous and coherent attitude. Finally, within the
      framework of the diseases examined here, search for lung disease caused by
      cytomegalovirus should not mask other organ localizations in, for example, the
      retina, the digestive tract.

PMID- 8746019
TI  - [Standard radiological characteristics of thoracic sites of tuberculosis in
      patients with AIDS in a Tunisian population].
AB  - Aspects of tuberculosis on the standard chest X-ray in a population of 18 AIDS
      patients in Tunisia were examined. The diagnosis of pulmonary tuberculosis was
      confirmed in all cases with bacteriology tests. Diffuse lesions of the parenchyma
      predominated contrasting with the exceptional nature of cavernous formations.
      Localized infiltrations were infrequent and intrathoracic node enlagement was
      rare. Cases with no abnormal radiological signs were also seen in advanced HIV
      infection. Such atypical cases, in agreement with data in the literature, would
      be explained by immunoradiologic correlation. Thus it is necessary to search for
      the tuberculosis bacilli in all patients with HIV infection whatever the aspect
      on the standard chest X-ray.

PMID- 8746020
TI  - [Ossified bronchial neuroendocrine tumors: 3 cases].
AB  - Large calcium deposits can occur in neuroendocrine tumours of the bronchi and
      have been observed more frequently with the development of tomodensitometry which
      is now used for the diagnosis of calcified lung tumours including neuroendocrine
      tumours. The knowledge of such calcified images should not however mask the
      possibility of a malignant tumour.

PMID- 8746021
TI  - [Normal values of respiratory function tests. Safety of normalized regression
      equations].
AB  - A frequent question in lung function testing is the extent of the margin of error
      in the measurements. Is the confidence interval (CI) of the usual summary
      equations for reference values larger than the sum of every possible error
      including interindividual variations and measurement errors which come from the
      apparatus, the technician and the patient? The analysis of the data of several
      authors including our data (lung function laboratory of Brest University
      hospital) leads to the conclusion that the summary equations of Quanjer et al.
      (1993) may be used safety as the CI is larger than the sum of all errors.
      However, this is only true if lung function testing is performed in optimal
      conditions, i.e. with frequently checked and carefully calibrated apparatus used
      by professional technicians in cooperating patients.

PMID- 8746022
TI  - [Posterior mediastinal mass].
AB  - Bronchogenic cyst of esophagus wall with intracystic haemorrhage in a patient
      with C hepatitis and portal hypertension. CT and MRI study.

PMID- 8746023
TI  - [Malignant triton tumor of the posterior mediastinum treated by thoracoscopic
      approach. Apropos of a case].
AB  - A tumour of the posterior mediastinum was removed via thoracoscopy. The histology
      report was a triton tumour. This is a rare (less than 80 cases reported in the
      literature) malignant tumour of the nervous system: malignant schwannoma with
      rhabdomyoblastic differentiation. The characteristics of this rare tumour and the
      consequences of videoassisted surgery in this specific case are discussed: a
      second access is required to widen the thoracotomy and complementary radiotherapy
      is needed.

PMID- 8746024
TI  - [Chronic obstructive bronchopneumopathy after acute inhalation of sulfur
      anhydride. Apropos of a case].
AB  - We report on an acute accidental inhalation of sulfurous anhydride, by a man aged
      thirty in the course of his work. This intoxication, followed by acute
      respiratory distress, first showed an improvement, then re-aggravation 26 days
      after the accident. This episode has not been explained. The patient then
      developed a chronic obstructive bronchopathy. Ten years of regular observation
      allows us to maintain that the severe obstructive syndrome which the patient
      presents has never regressed (FEV1/FVC = 32%), and must be associated with a
      chronic toxic obstructive bronchopneumopathy.

PMID- 8746025
TI  - [Can outcome of varicella pneumonia be predicted in a non-immunosuppressed
      patient?].
AB  - Varicella rarely occurs in the adult but can cause multi-organ complications. The
      most frequent (15 to 30% involve varicella pneumonia of unpredictable outcome. In
      the healthy adult, outcome can be favourable in 5 days or inversely lead to
      respiratory distress and death in 10 to 20% of the cases. An analysis of the
      published cases does not reveal any factor predicting unfavourable outcome. A
      register of varicella pneumonia would help identify potential predictive factors.

PMID- 8746026
TI  - [Uncommon complication of the use of implantable chambers in oncology].
AB  - The catheter of an implantable chamber migrated into the pulmonary infundibulum
      in a patient given chemotherapy for bronchogenic cancer. Current management of
      such cases is to remove the catheter under pulmonary angiography control using a
      basket system.

PMID- 8746027
TI  - [Hypoxemic nosocomial pneumonia developing in excavation in a patient with
      Cushing disease].
AB  - Multifocal alveolar hypoxaemic pneumonia caused by sporadic nosocomial infection
      led to acute respiratory failure and development of cavitations. Legionella
      pneumophilia type I was isolated. The patient was not in a state of
      immunosuppression other than that due to Cushing's disease recently treated
      surgically followed by corticosteroids. Specific clinical and radiological signs
      of Legionellosis (particularly the development of cavitation) and their mode of
      infection (community acquired or noscomial, sporadic or epidemic,
      immunocompetence or immunodepression) are discussed.

PMID- 8746028
TI  - [Food poisoning-infections in metropolitan France].
AB  - Food-borne diseases result from ingestion of contaminated foods, especially with
      pathogenic bacteria. It is considered as an outbreak as soon as 2 cases are
      diagnosed following a common food exposure; in France, declaration to health
      authorities is mandatory. Salmonella is the most frequently identified aetiologic
      agent. The incidence of Campylobacter induced food-borne infection is
      understated. Infections due to Staphylococcus or Clostridium perfringens
      represent almost 30% of all outbreaks. Listeriosis has to be included in food
      borne disease because of its severity, and since it determines outbreaks for
      which mandatory epidemiological survey is especially important.

PMID- 8746029
TI  - [Typhoid fever].
AB  - Endemic in regions with poor hygienic conditions, Enteric fevers are imported in
      France by returning travellers. They are caused by Salmonella strains, mainly S.
      Typhi, transmitted via fecal-oral route. Salmonella reach the blood stream after
      proliferating in mesenteric lymph nodes. At an initial stage blood and bone
      marrow cultures, later on Widal-Felix serology permit diagnosis. Antibiotics have
      rendered death exceptional. Quinolones and ceftriaxone allow treatments shorter
      than 10 days. Immunization (Typhim Vi) and improvement of hygienic standards are
      the cornerstone of prevention.

PMID- 8746030
TI  - [Diarrhea caused by antibiotic therapy].
AB  - Diarrhoea, or any change in bowel habits, occurs in up to 30% of the individuals
      treated by antimicrobial agents. Most cases of such diarrhoea are benign and
      secondary to a transient dysfunction of normal colonic flora induced by the
      antibiotic treatment. In some cases, the antibiotic-induced alteration of the
      normal gut flora leads to the establishment of pathogens, of which Clostridium
      difficile is the most important. C. difficile intestinal infection results in a
      wide spectrum of diseases, ranging from benign diarrhoea without colitis to life
      threatening cases of relapsing pseudomembranous colitis.

PMID- 8746031
TI  - [Infectious diarrhea in young children and infants].
AB  - Acute diarrhoea is one of the major causes of outpatient paediatric consultation,
      especially during infancy. An infectious cause should be suspected on the acute
      onset of diarrhoea associated with fever. The specific pathogen is seldom
      investigated and individualized. Rotavirus has been recognized as the most
      important enteric pathogen, particularly in infants during winter months. It may
      be responsible for nosocomial infections in hospital and outbreaks in day-care
      centers. Bacteria may cause a diarrhoea by elaboration of enterotoxins, by
      invasiveness, or both. Use of antibiotic is usually not necessary even in
      bacterial infections because they are self-limited. Choice of the antibiotic is
      complicated by the rapid emergence of resistant pathogenic strains. The first
      step is rapid assessment of the hydratation status of the patient. Fluid and
      electrolytes replacement is the mainstay in the treatment of infectious diarrhoea
      of any cause.

PMID- 8746032
TI  - [Infectious diarrhea in the aged].
AB  - Infectious diarrhoea in the elderly is associated with high morbidity and
      mortality and need early diagnosis and treatment. Polypathology, malnutrition,
      polytherapy, length of stay in the hospital and residence in nursing-home
      contribute to the increasing incidence and gravity of these diseases with aging.
      Viral gastroenteritis is responsible for epidemic in nursing-home residents.
      Bacterial gastrointestinal infections are primarily caused by enterotoxigenic
      agents inducing sporadic or epidemic infections food poisoning. Older adults are
      more particularly exposed to antibiotic-associated diarrhoea. Clostridium
      difficle has been increasingly recognized as a cause of pseudomembranous colitis
      in elderly and is associated with increased mortality. The approach to an old
      patient with suspected infectious diarrhoea should be to eliminate the likely
      noninfectious causes, to detect immediate complications due to hydroelectrolytic
      loss, to initiate early appropriated oral rehydration therapy so as to prevent
      dehydratation, to avoid the use of antimotility drugs, and to evaluate and to
      take over nutritional consequences of diarrhoea.

PMID- 8746033
TI  - [Travelers' diarrhea].
AB  - Up to fifty per cent of travellers going from temperate countries to tropical or
      subtropical countries present a diarrhoea. Enterotoxigenic Escherichia coli
      remain the most frequent bacterial cause, being identified in 40 to 70% of cases.
      Laboratory investigations are reserved to grave or protracted cases or those
      which resist to empirical therapy. Careful selection of food and beverage can
      limit its incidence. In adults at high risk of complications (sick or aged
      people) or who cannot suffer an interruption of their activity, one can prefer to
      a chemoprophylaxis with possible occurrence of adverse effects the early
      administration of a fluoroquinolone, which besides is a first-choice treatment of
      serious cases.

PMID- 8746034
TI  - [Cholera].
AB  - Cholera remains a great epidemic disease. The spread of the current pandemic due
      to Vibrio cholerae O1, the discovery of a permanent aquatic reservoir due to
      dormant state of vibrio, the occurrence in 1992 of the new pathogenic serotype
      O139 in India, and increasing antibiotic resistance are clear demonstration that
      this old disease is far from conquered. Clinical manifestations are due to the
      stimulation of enterocytic cAMP by vibrio's enterotoxin. Treatment by appropriate
      early rehydration is highly effective. During major outbreaks it requires
      "military logistics". Hygiene and chlorine remain the best prophylaxis; WHO's
      recommendations on the use of the new oral vaccines, effective against O1
      strains, will probably evolve as the results of ongoing trials will become
      available.

PMID- 8746035
TI  - [Diarrhea in immune deficiency status].
AB  - With a prevalence of approximatively 50%, diarrhoea is a frequent event in immune
      deficiency of any cause. Because this condition is permanent in AIDS, the main
      characteristic of diarrhoea is chronicity. Non infectious causes are more common
      in conditions other than AIDS with, for exemple, intestinal injuries related to
      graft versus host disease or to chemotherapy toxicity. Among infectious causes,
      enteric parasitic diseases such as cryptosporidiosis or microsporidiosis are more
      commonly observed in the immunodeficiency related to HIV while viral infections
      due to cytomegalovirus or adenovirus seem possible in any case of severe troubles
      of the immunity. Gram-negative infections and Clostridium difficile colitis have
      to be diagnosed because efficient treatment is available. In these patients
      usually in bad general condition, because diarrhoea is often of unknown aetiology
      or non curable, the diagnostic and therapeutic strategy has to be pragmatic in
      order to control the symptoms without an excess of invasive procedures.

PMID- 8746036
TI  - [Iatrogenic agranulocytosis. Etiology, diagnosis, treatment].

PMID- 8746037
TI  - [Autoimmune hemolytic anemia. Etiology, diagnosis, treatment].

PMID- 8746038
TI  - [Fractures of the distal end of the radius in adults. Mechanisms, diagnosis,
      treatment].

PMID- 8746039
TI  - [Fracture of the leg. Mechanism, diagnosis, treatment].

PMID- 8746040
TI  - [Dehydration. Etiology, physiopathology, diagnosis, treatment].

PMID- 8746041
TI  - [Cutaneous bacterial infections: impetigo. Etiology, diagnosis, development,
      treatment].

PMID- 8746042
TI  - [Crohn disease, hemorrhagic rectocolitis: antibodies and humans].

PMID- 8746043
TI  - Anti-endothelial cell antibodies in sera from patients with inflammatory bowel
      disease.
AB  - IgG anti-endothelial cell antibodies (AECA) have been described in sera from
      patients with vasculitis and other immune disorders such as systemic lupus
      erythematosus. Presence of AECA may be relevant to the hypothesis that Crohn's
      disease (CD) is a form of intestinal vasculitis. The aim of this study was to
      search for IgG AECA among 141 patients with CD, 94 patients with ulcerative
      colitis (UC) and 71 healthy blood donors and to assess the relationship between
      AECA and demographic or disease data. The cut-off point was defined from the mean
      OD values + 2 SD obtained from healthy blood donors. Seventeen percent of sera
      from patients with CD were positive for IgG AECA, whereas 24.5% of sera from
      patients with UC were positive. Among disease data, only a significant
      relationship between presence of IgG AECA and CD activity was noticed. These
      results might reinforce the hypothesis that intestinal vascular injury may be an
      important event in CD. However, detection of AECA in an almost similar percentage
      of patients with UC is more suggestive of an immune response to hidden
      endothelial self-antigen exposed after endothelial cell damage or a further
      marker of disturbed immunoregulation in inflammatory bowel disease.

PMID- 8746044
TI  - [Treatment of diversion colitis with short-chain fatty acids. Bacteriological
      study].
AB  - OBJECTIVES: Bacterial imbalance may be involved in the pathogenesis of diversion
      colitis, via diminished production of short chain fatty acids. The aim of the
      study was to evaluate the effectiveness of short chain fatty acids on microbial
      flora of patients with diversion colitis and to compare this flora to the
      microbial flora of controls. METHODS: We prospectively evaluated the
      effectiveness of short chain fatty acids irrigation on bacterial flora of the
      excluded colon in 13 patients (8 males, 5 females; mean age: 43.7 years). The
      causes of diversion were inflammatory bowel disease (n = 4) colonic cancer (n =
      2) sigmoid diverticulitis with perforation (n = 3) ischio-rectal abscess (n = 2)
      and miscellaneous (n = 2). Patients were given, twice a day for 14 days in a
      double blind manner, a 60 mL enema containing either short chain fatty acids
      (acetate: 60 mmol/L; propionate: 30 mmol/L; and n-butyrate: 40 mmol/L) (group 1;
      n = 7) or isotonic NaCl (group 2; n = 6). Bacteriological studies were carried on
      before starting the trial (D1) and 14 days later (D14). RESULTS: Before and after
      treatment, there was no difference between group 1 and group 2 concerning
      bacterial counts and species. Bacterial flora of patients with diversion colitis
      was characterized by: a) an increase of the count of aerobic bacteria; b) an
      increase of aerobic and aeroanaerobic species; c) the presence of black pigmented
      Gram negative anaerobic rods such as Prevotella intermedia and Porphyromonas
      asaccharolytica which were not found in rectal flora of the control group (16
      volunteers, mean age: 27 years). CONCLUSIONS: These data suggest that: a) enema
      with short chain fatty acids does not induce significant changes in the
      composition of the microbial flora in patients with diversion colitis; b)
      bacterial dysbiosis may be involved in pathogenesis of diversion colitis without
      involving the action of short chain fatty acids.

PMID- 8746045
TI  - [Sclerosing peritonitis. A series of 10 cases and review of the literature].
AB  - OBJECTIVE AND METHODS: The aim of this study was to describe the main features of
      sclerosing peritonitis, using a retrospective study in 10 patients. RESULTS: The
      main causes of sclerosing peritonitis were continual ambulatory peritoneal
      dialysis (n = 3), peritoneal chemotherapy (n = 2) and liver cirrhosis (n = 2).
      Sclerosing peritonitis was revealed by acute or chronic bowel obstruction (n =
      8). Small bowel X-rays and abdominal tomodensitometry showed a small bowel
      dilatation with a normal mucosa (n = 7), ascites (n = 5) as well as agglutination
      and fixation of small bowel loops within a cocoon (n = 3). Surgical viscerolysis
      was performed in 9 patients and allowed prolonged clinical remission in 4; 3
      patients died postoperatively (1 had a cirrhosis and 2 were treated with
      continuous ambulatory peritoneal dialysis), 1 patient had a complicated
      postoperative course with recurrent enterocutaneous fistulae. CONCLUSION:
      Sclerosing peritonitis may be suspected in a patient who presents a combination
      of bowel obstruction, small bowel dilatation without mucosal disease and ascites.
      Surgical viscerolysis is a dangerous operation associated with high mortality in
      patients with renal failure or cirrhosis.

PMID- 8746046
TI  - [Effect of pentagastrin on the survival of allogenic grafts from fetal rat
      intestine].
AB  - OBJECTIVES: Pentagastrin is not known as an immunomodulatoring drug. The aims of
      the present study were to create an optimal schedule for pentagastrin
      administration and to evaluate its influence on the allogenic foetal intestinal
      graft survival and the recipient condition in rats. METHODS: An allogenic foetal
      intestinal graft was performed in rats treated by pentagastrin 1 mg/kg/day and in
      controls. Biomorphometry and histology of the graft was regularly studied and
      biochemical, hematological, immunological and morphological parameters were
      determined in a maximal observation time of 19.5 months. RESULTS: Pentagastrin
      treatment, 1 mg/kg/day, significantly increased the graft survival in rats and.
      In 50% of the cases, tolerance was reached without any damage for the recipients.
      This may be due to additional effects of mild immunodepressive and trophic
      influences of pentagastrin, which have to be confirmed and which could be useful
      in adult intestine transplantation.

PMID- 8746047
TI  - [Genetics of inflammatory bowel diseases].

PMID- 8746048
TI  - [Hemorrhage caused by rupture of gastroesophageal varices: should we dilate the
      liver or strangulate the varices?].

PMID- 8746049
TI  - [Portasystemic anastomosis by transjugular approach: treatment of active and
      refractory hemorrhage caused by rupture of esophageal varices. Results in 11
      patients].
AB  - OBJECTIVE: The aim of this study was to assess the feasibility and efficacy of
      transjugular intrahepatic portosystemic shunts for refractory variceal bleeding,
      uncontrolled by sclerotherapy or endoscopic ligation. METHODS: 11 patients (mean
      age: 52 years) with cirrhosis admitted for refractory haemorrhage from ruptured
      oesophageal varices were included in this study. Eight patients were Child-Pugh
      class C. All patients were actively bleeding. RESULTS: All the procedures were
      successful. Variceal haemorrhage stopped within 24 h. There was no mortality
      during the procedure. Early complications such as rebleeding (18%) and thrombosis
      (18%) occurred. Thirty days mortality was 27%. Follow-up in the 8 surviving
      patients was 19.5 +/- 8 months. Three patients developed recurrent bleeding, from
      non-variceal sources in 2. In 4 surviving patients, occlusion of the shunt was
      treated with dilatation or insertion of a second stent. The incidence of hepatic
      encephalopathy was 25%. Five patients subsequently underwent liver
      transplantation. Among the 3 patients ineligible for transplantation, one died of
      hepatocellular carcinoma after 10 months. The 2 others were alive after 19 and 25
      months, respectively. CONCLUSIONS: These results suggest that transjugular
      intrahepatic portosystemic shunt is a safe and effective procedure of portal
      decompression in patients with refractory variceal bleeding. Prospective trials
      comparing this percutaneous procedure and surgical treatment are required.

PMID- 8746050
TI  - [Endoscopic ligation of esophageal varices: prevention of hemorrhagic recurrences
      caused by rupture of esophageal varices. Results in 45 patients].
AB  - OBJECTIVES: The aim of this study was to assess the morbidity and efficacy of
      endoscopic variceal ligation for the prophylaxis of rebleeding from oesophageal
      varices. METHODS: Forty-five patients with cirrhosis (Child's class: A: 18, B:
      16, C: 11) and recent (< 48 h) variceal bleeding were included. Eleven of the
      patients were included after failure of sclerotherapy. All patients were treated
      by endoscopic ligation until the complete eradication of oesophageal varices. The
      mean follow-up was 8.7 +/- 6.8 months. RESULTS: Oesophageal varices were
      eradicated in 40 patients (89%) after an average of 2 sessions (range: 1-5). In a
      subset of 11 patients treated after failure of sclerotherapy, 8 (73%) had
      complete eradication of oesophageal varices. Six of the 45 patients (13%) had
      recurrence of haemorrhage, due to post-ligation ulcerations in 5 cases and to
      rupture of oesophageal varices in one case. The rate of complications was 7%. Of
      the 40 patients whose oesophageal varices were eradicated, 7 (17%) were lost for
      follow up, and another treatment was performed in 4 (10%): liver transplantation
      in 2, and transjugular intrahepatic portosystemic shunt in 2. Recurrence of
      oesophageal varices after eradication was observed in 3 (10%) of the remaining 29
      patients after a follow-up of 8.9 +/- 12.9 months. Of these 3 patients, only one
      (3%) presented with recurrence of haemorrhage due to ruptured oesophageal
      varices. Three patients (7%) died before eradication of oesophageal varices from
      causes unrelated to the technique. CONCLUSION: This study confirms that
      endoscopic ligation is effective for eradication of oesophageal varices, with a
      low morbidity. This technique appears to be a method of choice in the prophylaxis
      of rebleeding from oesophageal varices, especially when sclerotherapy is
      ineffective.

PMID- 8746051
TI  - [Sclerotherapy versus ligation in hemorrhage caused by rupture of esophageal
      varices. Direct meta-analysis of randomized trials].
AB  - OBJECTIVES: To compare the advantages of endoscopic ligation and endoscopic
      sclerotherapy for bleeding esophageal varices, published randomized clinical
      trials were critically reviewed by meta-analysis. Only ten clinical trials
      concerning a history of recent or active bleeding esophageal varices were
      included. METHODS: The methodology, population, treatment and outcomes of each
      relevant trial were evaluated by duplicate independent review. RESULTS:
      Endoscopic sclerotherapy compared to banding ligation significantly increased the
      rate of rebleeding (OR: 1.6; 95% IC: 1.1-2.3) without increasing early mortality
      compared to endoscopic banding ligation (OR: 1.3; 95% IC: 0.8-1.9). The rate of
      varice eradication associated with these two types of treatment was not different
      (OR: 0.9; 95% IC: 0.6-1.3) but was obtained more quickly with endoscopic banding
      ligation (3.8 +/- 1.6 versus 5.8 +/- 2.2; P < 0.05). The rate of complications
      was higher after sclerotherapy (OR: 2.5; 95% IC: 1.7-3.7), in those cases with a
      positive heterogeneity test. CONCLUSIONS: This meta-analysis shows a lower
      morbidity with endoscopic banding ligation in patients with variceal hemorrhage.
      The most important advantage of endoscopic banding ligation was the reduction of
      the rate of rebleeding.

PMID- 8746052
TI  - [Techniques and indications of endoscopic treatment of esophago-gastric varices
      in 1995].

PMID- 8746053
TI  - [Lymphomas of the colon complicating hemorrhagic rectocolitis].
AB  - Colonic lymphoma is a rare complication of ulcerative colitis. We report two
      cases of B cell colonic lymphoma occurring in two patients who had a left-sided
      ulcerative colitis for 7 and 24 years respectively. The diagnosis was made during
      surgery in one case and at colonoscopy in the other. Complete remission was
      achieved after surgery and chemotherapy with a 8-year and 15-month follow-up
      respectively.

PMID- 8746054
TI  - [Inflammatory pseudotumor of the intestine caused by necrotizing vasculitis in
      the course of Horton disease].
AB  - The authors report a case of giant-cell arteritis involving the digestive tract,
      revealed by a subocclusive syndrome. It appeared to be an unusual pattern
      according to the location, the tumour aspect and the histologic appearance of a
      periarteritis nodosa type. The digestive involvement and the histologic
      appearance are discussed in a review of the literature, as well as the link with
      the periarteritis nodosa.

PMID- 8746055
TI  - [Liver cirrhosis and granulomatous hepatitis after prolonged ingestion of lysine
      acetylsalicylate].
AB  - We report the case of a 75-year-old woman who was hospitalized for serum
      aminotransferase elevation. She had taken 1 g/d of salicylate therapy (Aspegic
      1000) for 5 years, clorazepate for 10 years, naftidrofuryl for 8 months and
      quinapril for 3 months. Liver histology showed cirrhosis and granulomatous
      hepatitis. Discontinuation of salicylate therapy resulted in normalization of
      liver tests, although other drug administration was pursued. This observation
      suggests that salicylate therapy can induce cirrhosis.

PMID- 8746056
TI  - [Lymphocytic ascites revealing systemic mastocytosis].
AB  - Systemic mastocytosis is a chronic disease with proliferation of mastocytes in
      organs separate from skin. We report the case of a systemic mastocytosis revealed
      by a lymphocytic ascites in the absence of cutaneous involvement. The diagnosis
      was established by the ultrastructural examination of the bone marrow.
      Identification of few mastocytes in ascites suggested a mast cell infiltration of
      the peritoneum. A treatment by alpha-2b interferon was unsuccessful, and death
      rapidly occurred.

PMID- 8746057
TI  - [Acute pancreatitis and propylthiouracil].

PMID- 8746058
TI  - Association of coeliac disease and portal venous thrombosis.

PMID- 8746059
TI  - [Periostosis and Crohn disease: value of methotrexate].

PMID- 8746060
TI  - [Parietal impaction of an endoscopic percutaneous gastrostomy tube].

PMID- 8746061
TI  - [Excessive traction of an endoscopic gastrostomy tube causing migration into the
      abdominal wall].

PMID- 8746062
TI  - [Acute cholangitis caused by an amoxicillin-clavulanic acid combination].

PMID- 8746063
TI  - [Association of extrahepatic aneurysm of the hepatic artery and aneurysm of the
      portal trunk in a patient with liver cirrhosis].

PMID- 8746064
TI  - [A rare tumor of the liver: solitary plasmacytoma].

PMID- 8746065
TI  - [Treatment with recombinant interferon alfa-2a and pregnancy in a patient with
      chronic viral hepatitis C].

PMID- 8746066
TI  - [Acute hepatitis caused by exposure to lead].

PMID- 8746067
TI  - [Mutants of the pre-c region of the hepatitis B virus associated with severe
      recurrence after liver transplantation].

PMID- 8746068
TI  - With platelets, as with T lymphocytes, the blood cell system behaves as a neuron.

PMID- 8746069
TI  - Anatomy and physiology of headache.
AB  - Headache is a vast field with many different varieties of headaches and
      classifications. However, all headaches have a common anatomy and physiology. All
      headaches are mediated by the trigeminocervical nucleus, and are initiated by
      noxious stimulation of the endings of the nerves that synapse on this nucleus, by
      irritation of the nerves themselves, or by disinhibition of the nucleus. A
      mastery of the relevant anatomy and physiology of the trigeminocervical
      nociceptive system serves to predict and summarise the many varieties of headache
      systematically and with reference to their mechanisms.

PMID- 8746070
TI  - Classification of primary headaches.
AB  - In 1988, the International Headache Society (IHS) classification committee
      published operational diagnostic criteria for the primary headaches and a broad
      range of other headache disorders. These criteria have been translated into more
      than ten languages, providing uniform terminology for clinical practice,
      multinational clinical trials, and biologic and epidemiologic research. The
      criteria have also been evaluated in a number of field studies intended to
      address their generalizability, exhaustiveness, reliability, and validity. In the
      present publication the IHS criteria for migraine and tension-type headache are
      presented.

PMID- 8746071
TI  - Epidemiology of migraine.
AB  - The introduction of operational diagnostic criteria for the primary headaches in
      1988 has provided new opportunities for comprehensive epidemiologic headache
      research. In recent years, several studies on the epidemiology of migraine have
      emerged. This review deals with methodologic considerations and provides a
      snapshot of the main findings in these studies. The importance of epidemiologic
      studies in clarifying the natural history of migraine is elucidated.

PMID- 8746072
TI  - Discriminative stimulus properties of dextromethorphan in rats.
AB  - Male Sprague-Dawley rats were trained to discriminate dextromethorphan (DM, 30
      mg/kg, ip) from saline using a standard two-lever, fixed ratio 10, food
      reinforcement procedure. The DM-saline discrimination was acquired, and a range
      of doses of DM produced a dose-related generalization to the DM-lever choice.
      Stimulus generalization tests were conducted with dextrorphan, an active
      metabolite of DM, and with drugs selected from different pharmacological
      families. Dextrorphan induced a full generalization to DM, but only at a dose
      higher than the DM training dose. Morphine, a mu opiate receptors agonist, and U
      50488, a kappa opiate receptors agonist, failed to substitute for DM.
      Cyclazocine, a benzomorphan derivative, with high affinity for sigma receptors,
      was able to produce a complete generalization to DM, without a change in the
      number of rats responding. Dizocilpine (MK 801), a phencyclidine-like drug,
      produced a complete generalization, but only at a dose that markedly reduced the
      number of rats responding. Carbetapentane and caramiphen, antitussive drugs with
      high affinity for the 'specific DM receptors', failed to substitute for DM. These
      results show that the discriminative stimulus of DM, did not result primarily
      from its metabolism to dextrorphan; and the discriminative stimulus properties of
      DM appear to more closely resemble those of cyclazocine than those of the other
      drugs tested. This suggests a role of sigma receptors in the mediation of the DM
      stimulus. These experimental data are discussed with reference to the cyclazocine
      like subjective effects produced in man by large doses of DM.

PMID- 8746073
TI  - Metabolic and bone effects after administration of ipriflavone and salmon
      calcitonin in postmenopausal osteoporosis.
AB  - Forty postmenopausal women with bone mineral density (BMD) > 2 standard
      deviations below the mean value for healthy age matched controls were enrolled
      into an open controlled study to evaluate the metabolic and bone effects of
      ipriflavone (IP) versus salmon calcitonin (sCT) over a 12 month period. Both
      treatments significantly increased BMD after 6 and 12 months. A 4.3% increase of
      BMD was obtained in the IP treated group and a 1.9% in the sCT treated group
      after 12 months (p < 0.001 between treatments). Bone metabolism markers (serum
      osteocalcin, alkaline phosphatase, urinary calcium and hydroxyproline/creatinine
      ratio) were significantly reduced in both groups (p < 0.001). The reduction of
      urinary hydroxyproline/creatinine ratio was significantly greater (p < 0.05) in
      the IP group after 12 months. Both treatments were well tolerated. Four patients
      in the IP group reported gastralgia while two patients in the sCT group reported
      pruritus and one patient epistaxis.

PMID- 8746074
TI  - Can systematic research of hormone and growth factor receptors contribute to the
      recognition of acute and chronic types of breast cancer, of their specific
      mammary dysplasias, and of specific treatments?

PMID- 8746075
TI  - Growth factors and their receptors in neoplastic mammary glands.
AB  - Control of the growth of mammary glands is largely exerted in vivo by systemic
      hormones and locally-produced growth factors, whereas malignant tumours gradually
      lose the ability to respond to both types of control in vivo. However, the
      systemic hormones have little direct effect on stimulating the growth of rat or
      human mammary cell lines in vitro. Estrogens are thought to work by stimulating
      locally-produced growth factors and/or their receptors, eg transferrin, TGF alpha
      and IGF-1, and prolactin by a contaminating pituitary mammary growth factor
      (PMGF). Mammary stem cells intermediate between epithelial and myoepithelial
      cells are thought to be retained in malignant carcinomas, whereas the TGF alpha
      and bFGF-producing myoepithelial cells are lost. Hormonal autonomy of carcinomas
      may develop by overproduction of the locally-produced growth factors, their
      receptors (including related receptors, eg c-erbB-2) and/or by stem cells
      differentiating sufficiently to utilise normal control mechanisms, eg
      refractivity to PMGF and autocrine/paracrine response to bFGF. The failure of the
      stem cells to differentiate completely to myoepithelial cells in carcinomas
      greatly reduces the heparan sulphate proteoglycan sink used to sequester to bFGF
      in normal glands and also removes the possibility of eliminating cells by
      terminal differentiation, both processes possibly contributing to the
      uncontrolled growth of the malignant breast cell.

PMID- 8746076
TI  - Estrogen regulated messenger RNAs in human breast cancer cells.
AB  - A large number of estrogen-regulated mRNAs have been identified in human breast
      cancer cells. Some of these encode proteins whose regulation by estrogen had been
      established previously. Others have been identified by differential screening of
      cDNA libraries established from estrogen-stimulated breast cancer cells. The
      regulation of these RNAs by estrogens in different cell lines is reviewed. The
      possible role of their gene products where known is discussed as is the
      possibility that the proteins mediate the proliferative effects of estrogens on
      breast cancer cells. The possibility that measurement of one or more of these
      estrogen-regulated gene products in breast tumours might allow prediction of the
      likely benefit of patients from endocrine therapies is evaluated. Finally the
      impact that they have had on current understanding of how estrogens and
      antiestrogens regulate transcription of endogenous genes in human breast cancer
      cells is considered.

PMID- 8746077
TI  - Insulin-like growth factors and breast cancer.
AB  - Several years of research have indicated that the insulin-like growth factor
      (IGF) family of ligands, receptors and binding proteins are expressed in human
      breast cancer. The ligands are potent mitogens for breast cancer cell lines, and
      blockade of IGF signaling inhibits tumor growth. The IGFs can be regulated in
      normal and neoplastic tissue, indicating their important role in proliferation.
      For example, estrogen, a hormone important in the growth and progression of
      breast cancer is able to alter expression of IGF ligands, receptors and binding
      proteins. In addition, recent data now indicate that IGF ligands can also
      activate estrogen receptor (ER) in a ligand-independent manner. The apparent
      cross-talk between IGF and ER signaling is especially important to consider since
      anti-estrogens, such as tamoxifen, are a major modality for the treatment of
      breast cancer. Recent data suggest that IGFs may also be involved in tamoxifen
      resistance, through upregulation of the IGF-I receptor. Thus blockade of IGF
      signaling in combination with tamoxifen may prove to be a beneficial treatment
      for breast cancer patients.

PMID- 8746079
TI  - Lysosomal exocytosis induced by hyperthermia: a new model of cancer cell death.
      II. Effect on peritoneal macrophages.
AB  - Recently we described the "macrophagic lysosomal exocytosis" (MLE) as a possible
      new mode of cancer cell death induced by hyperthermia (HT) [1]. In order to
      confirm this first report, HT was applied at the peritoneum level with
      perfusional procedure, after catheter insertion under local anesthesia. We
      evaluated the subcellular changes of peritoneal macrophages in human gastric
      tumor, before and after hyperthermic treatment at 42 degrees C for 90 minutes.
      Transmission electron microscopy showed that treatment produced the disappearance
      of the cytoplasmic granules, with a consequent extracellular scavenger action of
      the phagocytic cells, the proliferation of some organelles such as mitochondria,
      endoplasmic reticulum and Golgi complex that may be addressed to a subsequent
      restoration of the granular pool in the degranulated macrophages. This phenomenon
      can enhance the already documented effect of hyperthermic perfusional
      chemotherapy in peritoneal tumors.

PMID- 8746078
TI  - Biological effect of active anti-IFN alpha immunization in HIV-infected patients.
AB  - Circulating interferon (IFN) was investigated in HIV-1 seropositive patients by
      measuring the IFN alpha antiviral effect in the serum. While serum of healthy
      seronegative individuals exhibits an antiviral effect, not due to IFNs,
      considered as background, serum of seropositive patients showed an additional
      antiviral effect due to the abnormal presence of IFN alpha. Increased titers of
      IFN alpha were found in the course of the HIV infection and seemed to correlate
      with the evolution of AIDS disease. Furthermore, patients immunized against IFN
      alpha had both stabilized CD4 cell count and decreased IFN alpha in their serum.
      HIV-1-infected patients also exhibited higher titers of natural anti-IFN
      antibodies than seronegative controls and the level of specific antibodies (Abs)
      markedly increased in immunized patients. Finally, serum from immunized patients,
      when compared to seronegative controls, exhibits an interferon neutralizing
      capacity.

PMID- 8746080
TI  - [Increase of sialic acid concentration in the plasma of patients with coronary
      disease].
AB  - OBJECTIVES: Plasma levels of sialic acid are elevated in patients with coronary
      heart disease. We evaluated the specificity of this increase and attempted to
      correlate it with the severity of coronary lesions. METHODS: Total plasma sialic
      acid levels measured in 60 control subjects were compared with that in 135
      patients with heart disease requiring coronarography. RESULTS: Plasma levels of
      sialic acid were significantly higher in patients (664 +/- 146 mg/l) than in
      controls (584 +/- 100 mg/l). In the group of patients, sialic acid level was only
      increased in those with coronary lesions - infarcts (738 +/- 166 mg/l) and angina
      (664 +/- 121 mg/l) - but was not raised above normal levels in those with other
      heart diseases (cardiomyopathy, valve failure, etc.). There was a positive
      correlation (p < 0.001) between raised sialic acid level and the severity of the
      coronary lesions as measured on coronarography. CONCLUSIONS: The elevated level
      of sialic acid in patients with coronary heart disease could be related to
      disorders in cell adhesion.

PMID- 8746081
TI  - [Anesthesia for cataract surgery. Result of a national survey].
AB  - OBJECTIVES: In order to evaluate the impact of recent progress in anesthesia and
      cataract surgery, we conducted a national survey in France to determine which
      techniques are used. METHODS: A questionnaire was sent to the most representative
      French ophthalmology teams: 66 teams participated in the survey. RESULTS: Seventy
      one percent of the surgeons routinely used phacoemulsification: 91% of the
      anesthesists prefer locoregional anesthesia: contraindications most often
      involved general health status (89%). Ambulatory anesthesia was preferred by
      16.7% of the teams. CONCLUSION: Phacoemulsification under peribulbal anesthesia
      is currently the technique most frequently used in cataract surgery in France.
      Ambulatory anesthesia is not yet widely used for this type of surgery.

PMID- 8746082
TI  - [Hepatic cytolysis caused by tocolytic treatment using micronized natural
      progesterone].
AB  - Micronized natural progesterone is often prescribed alone or in association with
      beta-agonists in the treatment of preterm labor in France. We observed drug
      induced hepatitis in 4 such patients. The main manifestation of liver disease was
      pruritus. After drug withdrawal, elevated transaminase levels continued to rise
      for one week then normalized within 10 to 30 days. The imputability of this
      undesirable effect was assessed and considered to be likely. The effectiveness of
      micronized natural progesterone in the prevention of premature delivery and in
      decreasing perinatal mortality and morbidity has not yet been proven. This drug
      should therefore be used with care, keeping in mind the risk of hepatitis,
      particularly in patients presenting with pruritus.

PMID- 8746083
TI  - [Left vocal cord paralysis in cytomegalovirus multifocal neuropathy in a patient
      with HIV infection].
AB  - Cytomegalovirus multifocal neuropathies (CMV-MN) in patients with AIDS are much
      less frequent than meningoradiculitis. We report here the case of a patient with
      AIDS hospitalized because of severe motor weakness and paralyzed left true vocal
      cord (PVC), related to a multifocal neuropathy. CSF analysis was normal with a
      negative PCR for CMV, but neuromuscular biopsy showed typical CMV inclusions. The
      patient's condition improved with high dose foscarnet therapy, followed by a
      combination of ganciclovir plus foscarnet, during a five-month follow-up period.
      Twenty three case reports of CMV-MN have been published in the literature, only 2
      of them presenting with a PVC. Extraneurological CMV involvement was usually
      documented. PCR for CMV in CSF was most often positive. However CMV inclusions
      were not frequently observed. The patients were usually improved under therapy
      with usually ganciclovir but relapse was observed in fifty percent within 3 to 6
      months despite secondary prophylaxis.

PMID- 8746084
TI  - [Gaucher disease].
AB  - Gaucher disease, a condition transmitted by autosomal recessive inheritance,
      results from a genetic defect in beta-glucosidase, an enzyme which degrades
      sphingolipids. Deficiency in beta-glucosidase leads to accumulation of its
      substrate, glycosylceramide, in macrophages and, in the more severe cases, in
      neurons. Clinically, splenomegaly, hepatomegaly, bone destruction, cytopenia, and
      in some cases, central neurological lesions develop. Three phenotypes have been
      described according to the absence (type 1) or presence of neurological
      involvement (type 2: severe, type 3: intermediate severity). The disease occurs
      in patients of all ethnic origins but type 1 is particularly well known in
      Ashkenese Jews and type 3 is found in the Swedish province of Norrbottnie. About
      forty mutations of the beta-glucosidase gene have been identified. Four account
      for 80% of the known mutations (1226G, 1448C, 84GG, IVS2+1). Residual enzyme
      activity of mutant beta-glucosidase explains some of the phenotypic variations.
      The phenotype resulting from the 1226G mutation has sufficient enzyme activity
      for degradation of gangliosides in the brain, explaining the absence of
      neurological involvement in patients with this allele. Treatment is based on
      enzyme supplemention: blood parameters return to normal and the volume of the
      spleen and liver are greatly reduced after 6 months. In infants with very severe
      disease, bone marrow graft may be used.

PMID- 8746085
TI  - [Viral origin of Paget's disease of bone?].
AB  - The viral aetiology of Paget's bone disease was suspected by the finding, in
      1974, of microcylindric paramyxovirus nucleocapsid-like inclusions in nuclei and
      cytoplasm of pagetic osteoclast. Paramyxovirus antigens were detected, using
      monoclonal antibodies, in the osteoclasts of pagetic lesions. Paramyxovirus RNA
      sequences were identified in Paget's bone tissue, predominantly in osteoclasts,
      using specific hybridization. However, these last results are conflicting because
      some reports failed to reproduce hybridization with Paramyxovirus. Nevertheless,
      Paramyxovirus could be responsible for the cytopathologic aspect of
      multinucleated osteoclasts for the stimulation of hyperexpression, in Paget's
      disease, of interleukin 6 and of c-fos oncogene known to enhance osteoclastic
      resorption activity.

PMID- 8746087
TI  - [Bone remodeling in fasting].

PMID- 8746086
TI  - [Transmission of human immunodeficiency virus to the fetus during pregnancy].
AB  - Estimates of the rate of human immunodeficiency virus vertical transmission range
      from 15% to 40%, and the rate is lower in European and American studies than in
      African studies. There appears to be a relationship between maternal factors,
      mode of delivery and mother-to-child transmission. The risk factors or markers
      associated with increased vertical transmission are analyzed in this review. The
      use of zidovudine, administered to HIV-infected women during pregnancy and
      labour, and to the offspring for 6 weeks reduce the mother-to-infant transmission
      rate from 25% to 8%. Other strategies to alter transmission of HIV, including the
      use of combinaison of anti-retroviral drugs, immunoprophylaxis against HIV or
      obstetric interventions needs to be evaluated.

PMID- 8746088
TI  - [Neurinoma with sudden-onset deafness].

PMID- 8746089
TI  - [Respiratory distress syndrome in an adult secondary to Mycoplasma pneumoniae
      infection].

PMID- 8746090
TI  - [Fever caused by medifoxamine].

PMID- 8746091
TI  - [Pregnancy during substitutive treatment for premature menopause].

PMID- 8746092
TI  - [Reactivation of hepatitis B in AIDS].

PMID- 8746093
TI  - [Mechanisms of rupture of indwelling central venous catheters. 2 cases].

PMID- 8746094
TI  - [Genetic susceptibility to malaria in man: contribution of genetic epidemiology].

PMID- 8746095
TI  - [Value of media containing chromogenic substrates for the identification and the
      listing of urinary bacteria].
AB  - Performance in terms of enumeration, growth and identification with a new culture
      medium (CPS ID2, bioMerieux) was evaluated using 405 urine samples and 244
      collection strains. The CPS ID2 medium contains chromogenic substrates enabling
      the detection of 4 bacterial enzymes which leads to the identification of
      colonies: Escherichia coli, Proteus mirabilis, Proteus-Morganella-Providencia and
      enterococci. No discrepancies in the enumeration were observed with the collected
      strains and urine samples. Sensibility and specificity of the identification of
      Proteae taxa (TDA +) and enterococcal taxa (Gram positive cocci and beta
      glucosidase +) was 100% using urine samples and 95.1% of E. coli strains (beta
      glucuronidase +, indole +) are detected. Routine use of this new medium for the
      bacterial examination of urine is satisfactory and an ultra-violet lamp is no
      longer required for reading as was the case previously with media containing
      fluorogenic substrates.

PMID- 8746096
TI  - [Informative capacity of 8 serological tests in the diagnosis of human
      brucellosis].
AB  - Assessment of the informative value of 8 immunological tests: sero-agglutination
      (Wright and Rose Bengale), indirect immunosorbent assay, counter immuno
      electrophoresis, ELISA IgG, IgM and IgA, and particle counting immunoassay
      (PACIA) has been performed among the results of serum of 209 patients. The
      patients were divided in four groups: 71 who already had brucellosis, 18 Yersinia
      infections, 12 Tularemia and 108 free of desease. The informative capacities of a
      positive result of counter immuno electrophoresis (Protein antigen Brucellin-INRA
      Tours-Nouzilly) is higher than others reactions and can be proposed as a
      confirmatory test of brucellosis. Among others techniques, 4 were found to be
      more sensitive: Elisa IgA (se = 97.6) and IgG (se = 90.1), IFI (se = 91.5) and
      Rose Bengale (se = 85.9) and can be proposed as screening test for medical
      diagnosis or epidemiological survey. Many cross-reactions were observed specially
      with Yersinia enterocolitica even with new serological methods.

PMID- 8746097
TI  - [Resistance to amoxicillin and amoxicillin-clavulanic acid combination of 231
      clinical strains of Escherichia coli, isolated in 1992 at the Cochin Hospital].
AB  - Among 231 clinical strains of Escherichia coli tested during may 1992, 89
      isolates (38.5%) were resistant to beta-lactams. The resistant strains were
      principally recovered from urinary and genital specimen from medicine and
      surgical departments. MICs of beta-lactams were determined alone or combined with
      clavulanic acid, and beta-lactamases were identified by isoelectric point
      characterization and by enzymatic inhibition tests. Among the resistant strains,
      92.1% were secreting a penicillinase and 6.7% a cephalosporinase. No extended
      spectrum beta-lactamase was observed. 85.5% of penicillinases were TEM-1 enzymes,
      4.9% SHV-1 beta-lactamase, 1.1% OXA-1 beta-lactamase and 8.5%, 7 strains, were
      IRT beta-lactamases (formerly called TRI). For 24 clinical E. coli strains, the
      MICs values were > or = 32 mg/l for amoxicillin plus clavulanic acid. The 7 IRT
      beta-lactamases showed the highest MICs, 256 to 4096 mg/l. Four of them exhibited
      a beta-lactamase of pI 5.4 and 3 a beta-lactamase of pI 5.2. The IRT beta
      lactamases represent 3% of all the Escherichia coli strains. This frequency is
      comparable or lower than the values reported by other studies conducted between
      1992 and 1994.

PMID- 8746098
TI  - Diurnal urinary excretion of cortisol and aldosterone in kidney graft recipients.
AB  - In 13 supine kidney graft recipients in the late post-transplant period the
      circadian rhythms of urinary cortisol and aldosterone excretion were studied. An
      inversion of the circadian rhythm of urinary cortisol excretion was found, with
      acrophase occuring in the night time. Plasma cortisol level, measured in 6 h
      intervals, attained the maximal mean value at 24 h. Urinary aldosterone excretion
      in most of the patients demonstrated also an inversed circadian rhythm with
      acrophase occuring from 21 to 03 h. In 6 patients the 24 h urinary aldosterone
      excretion was above the upper limit for healthy persons. The peak plasma
      aldosterone level was found at 24 h; it greatly exceeded the upper limit of
      aldosterone level in healthy supine persons. In 5 out of 13 patients the plasma
      renin activity (PRA) was above the upper limit of normal for supine subjects. The
      maximal mean PRA level was found at 24 h. The study in kidney graft recipients
      has established an inversed circadian rhythm of urinary cortisol and aldosterone
      excretion, probably related to the immunosuppressive treatment and reduced kidney
      function.

PMID- 8746099
TI  - [Ocular toxoplasmosis: value of immunoblotting for the determination of an intra
      ocular synthesis of antibodies].
AB  - The aim of this study was to demonstrate the intraocular synthesis of specific
      antibodies in case of Toxoplasma retinochoroiditis on the basis of immunoblot
      analysis. Vitreous or aqueous and serum were analyzed by immunoblot in four cases
      of toxoplasmic chorioretinitis. The same assays were performed on samples from 16
      control subjects. Immunoblot analysis of serum and ocular fluid from patients
      with toxoplasmic chorioretinitis showed IgG and IgA specific antibodies.
      Recognition patterns were different and demonstrated neo-antibodies in ocular
      fluid. In control samples only IgG were found and the same patterns were observed
      in the two compartments. Immunoblot is a useful technique to demonstrate the
      local synthesis of antibodies in ocular toxoplasmosis by comparison of
      recognition patterns between serum and ocular fluids. Integration of immunoblot
      patterns allows quantification of antibodies specific for each Toxoplasma antigen
      in the two compartments.

PMID- 8746100
TI  - [Is it still possible to reduce the incidence of nephrotoxicity of
      aminoglycosides?].
AB  - Aminoglycosides are still widely used alone or in combination with a beta-lactam
      antibiotic for the treatment of severe Gram negative infection. Oto- and
      nephrotoxicity are the major side effects associated with the use of these drugs.
      Although several risk factors associated with aminoglycoside nephrotoxicity have
      been identified, only few therapeutic approaches were suggested to reduce the
      incidence of their toxicity in patients. The single daily injection is the only
      approach actually used to reduce the renal toxicity of aminoglycosides in
      patients. However, the relationship between the nephrotoxicity of aminoglycosides
      and the time of the day these drugs should be given has never been explored in
      patients. Data obtained in laboratory animals indicated that temporal variations
      can be detected in the renal toxicity of aminoglycosides: the nephrotoxicity was
      observed during the rest period of the animals while no toxicity was found at
      other times of the day. Other studies suggested also that food intake can
      modulate the temporal variations in the nephrotoxicity of aminoglycosides. A
      better knowledge of the risk factors associated with the renal toxicity of
      aminoglycosides, a reduction in the number of daily injections of
      aminoglycosides, administration of aminoglycosides at the time of the lowest
      toxicity of the drug in patients submitted to an appropriate diet are the most
      interesting approaches to reduce the incidence of the renal toxicity of these
      agents.

PMID- 8746101
TI  - [Granulated CD56 lymphocytes of decidual tissue].
AB  - The reproduction is a complex mechanism wich is subtly immunoregulated since the
      semiallogenic fetus is not rejected by the mother. At the feto-maternal tissue
      interface, where fundamental mechanisms of tolerance occur, a large and unusual
      lymphocytes population takes place. These cells recruited during the earlier
      stages of pregnancy are very granulated and express brightly the N-CAM molecule
      (or CD56) with numerous adhesion and activation molecules. Nevertheless, they
      seem fonctionnally inactivated. They phenotypically belong to the peripheral
      blood minor fraction of NK cells which are CD56++CD16-CD3-. Although their
      function in the establishment of the gestation is not clearly known, because of
      their phenotypical heterogeneity, they may have two distinct functions:
      cytotoxicity and suppression. Their cytokine pattern, preferentially of the Th1
      type, inform us about their potential functions and their interactions with other
      cells populations in this tissue, allowing us to understand the main mechanism in
      the establishment of the pregnancy.

PMID- 8746102
TI  - [Performances of two kits for parathyroid hormone-related peptide (PTHrP) assay
      in the additional study of malignant hypercalcemias].
AB  - Measurement of parathyroid hormone-related peptide (PTHrP) associated with that
      of parathyroid hormone, allows to establish, in most cases, diagnosis of
      hypercalcemia of malignancy and more exactly of patients with Malignancy Humoral
      Hypercalcemia (MHH). Because of the variety of molecular forms of PTHrP, linked
      to its catabolism, its immunoassay remains difficult. After a study evaluating
      the methodological reliability, we measured the contribution of PTHrP to the
      hypercalcemia by 2 assays: a N-terminal RIA and a 1-72 IRMA in samples from 47
      control subjects, 10 patients with chronic renal failure (IRC), 13 patients with
      primary hyperparathyroidism (HPT), and 48 patients with solid tumors classified
      by their level of calcemia: 48 normocalcemia and 23 hypercalcemia. We noted a
      strong correlation (r = 0.92) between the two assays. They do not show increases
      in renal insufficiency; they have a good diagnostic discrimination between HPT,
      normal subjects and patients with MHH. Elevated levels of PTHrP are similar in
      both assays. However, IRMA appears to be more sensitive and more practical than
      RIA. Moreover, it shows the best correlation between serum calcium and phosphorus
      in patients with MHH.

PMID- 8746103
TI  - [Calcium carbasalate-metoclopramide combination versus dihydroergotamine in the
      treatment of migraine attacks].
AB  - In this randomised, double-blind, cross-over study the association of calcium
      carbasalate+metoclopramide was compared with oral dihydroergotamine mesilate in
      the treatment of migraine attacks. 155 patients suffering from migraine, with or
      without aura were analysed; the main efficacy criteria being the evolution of the
      headache intensity: disappearance of headache 2 hours after administration or
      incomplete improvement (severe to moderate headache reduced to slight headache).
      There was a significantly greater reduction in headache intensity following
      administration of CSC-METO (p < 0.001), the percentage of patients showing
      recovery or improvement two hours after administration being 64.5% with CSC-METO
      compared to 43.5% with DHE. A significantly more marked improvement following
      administration of CSC-METO was also observed for nausea, photophobia,
      phonophobia, use of analgesic treatment, impact on normal activities and overall
      assessment by the patient and physician. The frequency of undesirable events was
      weak and identical for both treatments.

PMID- 8746104
TI  - [Comparative trial of the clinical efficacy and tolerance of cefatrizine
      (Cefaperos) and cefpodoxime proxetil (Orelox) in superinfections of chronic
      obstructive bronchopneumopathies in adults in urban practice].
AB  - In order to compare the clinical efficacy and safety of cefatrizine (Cefaperos)
      and cefpodoxime proxetil (Orelox) in the treatment of secondarily infected
      chronic obstructive pulmonary disease (COPD) in adults, a multicentre,
      randomized, open study was conducted by 60 general practitioners in two parallel
      groups of patient suffering from COPD complicated by an acute episode of
      superinfection (Anthoniesen stages 2 and 3). After verification of the
      eligibility criteria, written consent and randomization, the patients received,
      for 10 days, either cefatrizine at the dose of 1 g/day or cefpodoxime proxetil at
      the dose of 400 mg/day. A self-assessment form was given to the patient. A
      telephone visit was planned for D3. The final visit on D11 +/- 1 evaluated
      clinical efficacy (success or failure) and safety. The study population was
      composed of 250 patients with a mean age of 59.9 +/- 15.9 years (sex ratio M/F =
      1.5). The principal etiology of COPD was chronic bronchitis in 67.5% of patients,
      longstanding asthma in 24.5% and emphysema in 6.8%. The mean history of the
      disease was 13.0 +/- 10.8 years. The Anthoniesen score was equal to 2 in 73.6% of
      patients, 3 in 8.8% of patients and 1 in 17.6% of patients. No significant
      difference concerning these criteria was observed between the two study groups.
      The clinical success rate was equivalent in the two groups. The time to
      regression of clinical signs tended to be shorter, up until the sixth day (mainly
      between D4 and D6) for patients treated with cefatrizine (p = 0.09; NS). The
      clinical safety was considered to be good and was comparable in the two study
      groups. This study concluded on the equivalent clinical efficacy of cefatrizine
      and cefpodoxime proxetil in the treatment of superinfections of COPD in general
      practice (97.5% and 99%, respectively), with a satisfactory and comparable
      safety, but with a much lower cost of treatment for cefatrizine. This conclusion
      is particularly important in the context of opposable medical references, as,
      although the treatment of superinfections of COPD by second and third generation
      cephalosporins is frequently proposed, the prescription of a less expensive
      cephalosporin appears to be more relevant.

PMID- 8746105
TI  - From targets to genes: a brief history of radiosensitivity.
AB  - The biological work of Douglas Lea spanned the period from 1934 to his early
      death in 1947, and during this short period he made important contributions to
      the theory of radiation action. He interpreted experimental data relating to the
      effects of radiation on viruses, bacteria, bean roots, etc in terms of the
      inactivation of discrete targets, which he identified with cellular genes. He
      thus laid the foundation of much subsequent research. It is now well recognized
      that mammalian cells differ substantially in radiosensitivity, especially in the
      low-dose region of the survival curve. The dependence of radiosensitivity on dose
      rate has been widely studied; this has practical significance for clinical
      radiotherapy as well as mechanistic implications. Since Lea's time there have
      been a number of efforts to describe models that can relate cell killing to
      radiation dose, dose rate, and track structure. So far these have not led to a
      comprehensive and widely accepted picture. Microdosimetric considerations lead to
      the concept of differing severity of lesions induced in DNA. Much is known about
      the sequence of processes that subsequently lead to cell inactivation: this can
      be divided into phases of induction, processing, and manifestation. Chromosomal
      events are currently attracting much attention, as they did in Lea's time.
      Considerable progress has also been made in identifying genes that control the
      repair of radiation damage. It has been found that mutation is frequently
      associated with the loss of a large segment of the genome around the damage site
      and this will have important implications for interactive processes between
      particle tracks.

PMID- 8746106
TI  - A mathematical model for light dosimetry in photodynamic destruction of human
      endometrium.
AB  - We are involved in the development of photodynamic therapy (PDT) as a minimally
      invasive method for treating dysfunctional uterine bleeding, one of the primary
      clinical indications for hysterectomy. In this paper, we analyse light
      propagation through the uterus in order to specify the requirements for a light
      delivery system capable of effectively performing endometrial PDT. Our approach
      involves developing an analytical model based on diffusion theory to predict
      optical fluence rate distributions when cylindrical and spherical optical
      applicators are placed in the uterine cavity. We apply the results of our model
      calculations to estimate the thermal effects of optical irradiation and the
      effective photodynamic optical dose. Theoretical fluence rate calculations are
      compared to fluence rate measurements made in fresh, surgically removed human
      uteri. Our results show that a trifurcated cylindrical optical applicator
      inserted into the human uterus can provide a light dose that is sufficient to
      cause photodynamic destruction of the entire endometrium. When the optical power
      per unit length of each cylindrical applicator is 100 mW cm-1 (at 630 nm), a
      fluence rate of 40 mW cm-2 is delivered to the boundary layer between the
      endometrium and the myometrium (a depth of about 4-6 mm). The optical fluence
      delivered to the boundary layer after 20 min of exposure is 50 J cm-2, a level
      that is generally accepted to cause tissue damage throughout the endometrium in
      most patients.

PMID- 8746107
TI  - Limiting values of backscatter factors for low-energy x-ray beams.
AB  - Models for the calculation of upper and lower limiting values to the backscatter
      factor (BSF) are presented. The upper limit is obtained from Monte Carlo
      simulations of infinite parallel beams incident on semi-infinite phantoms with
      the dose contributions from all orders of photon scatter considered. The lower
      limits are calculated using an analytical photon transport model which considers
      only the primary dose and the scatter dose from photons that have undergone
      single scattering interactions in the phantom. The limiting values can be used to
      evaluate measured and modelled BSF values for x-ray beams with photons of < or =
      150 keV. A parametrization of the limiting values in terms of photon energy and
      irradiation field size is presented so that results determined for monoenergetic
      beams can be extended to polyenergetic spectra. The utility of the limits is
      illustrated by comparisons made with BSFs from the literature.

PMID- 8746108
TI  - Triexponential decomposition of 1H spin-lattice relaxation decay curves of
      paramagnetically doped red cell suspensions at 7 T.
AB  - The spin-lattice relaxation behaviour of protons in paramagnetically doped red
      cell suspensions at two haematocrit levels has been studied using high-field (7
      T) inversion recovery data. The resulting relaxation decay curves were found to
      be best characterized by triexponential functions. The two-site exchange model,
      generally applied to biexponential relaxation data in calculating red cell water
      exchange parameters, was applied to the two fastest-relaxing fractions of the
      triexponential fits. The intracellular to extracellular water exchange rates so
      obtained were in good agreement with literature values. Additional exchange
      parameters including intracellular and extracellular water volume fractions and
      extracellular relaxation rates were also calculated directly from the relaxation
      data and found to be consistent with sample haematocrits and with independent
      relaxation rate measurements of the resuspension medium. The small-amplitude,
      slowly relaxing third component recovered from the triexponential fits of the
      relaxation data is attributed to intracellular haemoglobin protons.

PMID- 8746109
TI  - Measurement of dynamic wedge angles and beam profiles by means of MRI ferrous
      sulphate gel dosimetry.
AB  - The purpose of this study is to examine the possible value of measuring the dose
      distribution in dynamic wedge photon beams using ferrous sulphate gel phantoms
      analysed by MRI. The wedge angles and dose profiles were measured for a field
      size of 70 x 70 mm2 and for dynamic wedge angles of 15 degrees, 30 degrees, 45
      degrees and 60 degrees using a 15 MV photon beam generated from a Clinac 2100 CD
      (Varian). The dose profiles obtained from MRI ferrous sulphate gel were in good
      agreement with the dose measurements performed with a diode detector array. Also,
      the wedge angles determined from the MRI ferrous sulphate gel agreed well with
      the values obtained by using film dosimetry and with calculations by use of TMS
      (treatment planning system) (Helax, Uppsala, Sweden). The study demonstrated that
      MRI ferrous sulphate gel dosimetry is an adequate tool for measurements of some
      beam characteristics of dynamic radiation fields.

PMID- 8746110
TI  - The investigation of different cameras for in-beam PET imaging.
AB  - In situ and in vivo treatment plan verification and beam monitoring as well as
      dose control during heavy-ion tumour therapy can be performed in principle by
      measurements of range distributions of beta(+)-emitting nuclei by means of PET
      techniques. For this purpose the performance of different types of positron
      camera as well as the results of in-beam PET experiments using beams of beta(+)
      active heavy ions (15O, 17F and 19Ne with energies of 300-500 A MeV) are
      presented. Following the deduced performance requirements a PET scanner that is
      designed for clinical use in experimental heavy-ion therapy at GSI Darmstadt has
      been built. This limited angle tomograph consists of two large-area detector
      heads based on position sensitive BGO detectors and is predicted to perform the
      measurement of the end point of a beta(+)-emitting ion beam for the verification
      of a treatment plan with a precision better than 1 mm. The maximum dose applied
      in the patient thereby is of the magnitude of 10 mGy.

PMID- 8746111
TI  - X-ray induced luminescence and spatial resolution of La2O2S:Tb phosphor screens.
AB  - Absolute efficiency and modulation transfer function of laboratory prepared
      La2O2S:Tb phosphor screens of various coating thickness were studied. Detailed
      experimental data on the variation of absolute efficiency with x-ray tube voltage
      up to 200 kVp and screen coating thickness in transmission and reflection
      observation mode are given. Data were compared with similar results from other
      rare earth phosphor materials. Theoretical calculations were in good agreement
      with experimental data to permit estimation of intrinsic efficiency and
      coefficients related to light scattering and absorption within the phosphor
      material. The MTF of La2O2S:Tb screens was also experimentally and theoretically
      evaluated.

PMID- 8746112
TI  - A comparison of speeds of personal computers using an x-ray scattering Monte
      Carlo benchmark.
AB  - In recent years personal computers, PCs, have become more popular and competitive
      with other computers, in terms of price and memory, to run Monte Carlo (MC)
      programmes. A few years ago some work was performed to test computer speed,
      mainly other than PCs, using the MC code EGS4. In the present work a Monte Carlo
      neutron and photon code, MCNP version 4.2 and 4A, was used to test the speed of
      various PCs. A benchmark was written, with previously checked results, to test
      the PCs' speed. PCs used in the test were based on the Intel 486 (33, 66 and 100
      MHz) and pentium 90. The benchmark was also used on an upgraded SunSparcstation
      4/360. The pentium speed was found ot be about 3.5, 2 and 1.5 times faster than
      that of the 33, 66 and 100 MHz, respectively. The 33 MHz speed was comparable to
      that of the SunSparcstation. It is concluded that the application of MC code, the
      cost of the PC and the required speed of results may influence the choice of the
      PC.

PMID- 8746113
TI  - Fat media-hype greets obesity genes: is industry among the potential losers?

PMID- 8746114
TI  - Using bioinformatics in drug discovery.

PMID- 8746115
TI  - Structural limitations to antigenic mimicry achievable with retroinverso (all-D
      retro) peptides.

PMID- 8746116
TI  - Chemokines: progress toward identifying molecular targets for therapeutic agents.
AB  - Leukocyte migration towards injury sites is directed by the interaction of
      chemokines with their receptors. The stages of migration are closely regulated
      events that involve chemokine-induced leukocyte adhesion, diapedesis and homing.
      Current research suggests a pathophysiological role for chemokines in diverse
      inflammatory states arising from viral, bacterial and parasitic infection,
      allergic and asthmatic reactions, atherosclerosis and arthritis. A role for
      chemokines in tumor immunity and angiogenesis has recently been demonstrated. A
      basis for the rational design of chemokine antagonists is emerging from a
      knowledge of tertiary structures and mutational analysis of chemokine ligands and
      receptors. Here, we discuss advances in knowledge about chemokine structure and
      function, with emphasis on potential therapeutic agents.

PMID- 8746117
TI  - Immunoadhesins: principles and applications.
AB  - The prototypic immunoadhesin is an antibody-like molecule that fuses the Fc
      region of an immunoglobulin and the ligand-binding region of a receptor or
      adhesion molecule. In this article, we review some important structural and
      functional principles of immunoadhesins. In addition, we highlight some unique
      advantages of immunoadhesins as experimental tools in biology, as well as some of
      their exciting potential applications in medicine.

PMID- 8746118
TI  - Novel antimicrobial compounds identified using synthetic combinatorial library
      technology.
AB  - The recent emergence of combinatorial chemistry has greatly advanced the
      development of biologically active lead compounds. It is anticipated that
      combinatorial library technology will add great value to the fight against drug
      resistant bacterial strains, which pose increasingly serious health hazards.
      Owing to the need to use complex cell-based assays and, in turn, to screen free
      compounds in solution, the potential use of combinatorial libraries in the field
      of infectious diseases has not yet been fully explored. Despite these
      limitations, a number of new antimicrobial and/or antifungal compounds have been
      successfully identified from pools of millions of other compounds.

PMID- 8746119
TI  - Carbon monoxide--does fetal exposure cause sudden infant death syndrome?
AB  - The epidemiological features of sudden infant death syndrome (cot death) include
      a peak incidence between 8 and 13 weeks of age, a time of death or conception
      occurring during the winter months and an excess of deaths in infants born to
      young multiparous women of low socioeconomic status who smoke. We suggest that,
      through hypoxia, carbon monoxide in tobacco smoke and in the home exerts a
      noxious effect on the developing central respiratory control mechanism of the
      fetal brain which then remains particularly susceptible to further insults in the
      early postnatal period from infection and hyperthermia, resulting in death from
      central respiratory dysfunction.

PMID- 8746120
TI  - Destruction of human immunodeficiency-infected cells by ferrofluid particles
      manipulated by an external magnetic field: mechanical disruption and selective
      introduction of cytotoxic or antiretroviral substances into target cells.
AB  - Submagnetic domain magnetic fluid particles of approximately 10 nm average
      diameter complexed with CD4 or monoclonal antibody and then injected into the
      patient, will localize to the cell membrane of the target cell. These ferrofluid
      particles will interact with an externally applied rotating magnetic field of
      rapidly changing polarity. Under these conditions, the ferrofluid particles will
      be drawn into a circular path and an axial spin will be induced as each particle
      aligns itself with the magnetic force lines. A portion of these magnetic fluid
      particles will be drawn into the target cell membrane and into the cytoplasm
      causing brief perforations of the cell membrane of the target cells. If enough
      mechanical damage is done to the plasma membrane or to the intracellular
      structures, cell lysis may result, but in any case the brief disruptions of the
      target cell membrane can be used to selectively introduce membrane impermeant
      cytotoxic or antiretroviral substances into the target cell while relatively
      sparing normal cells.

PMID- 8746121
TI  - Genetic abnormalities and oncogenesis.
AB  - Since the development of carcinoma probably depends on the paralyzed mitotic
      maturation promoting system present only within the cancer cell's cytoplasm, it
      must be established within the cytoplasm, not within the nucleus. Hence, genetic
      abnormalities in the nucleus should not be regarded as responsible for
      oncogenesis, even though they may always be identified specifically in a certain
      carcinoma alone and generally be regarded as responsible for the oncogenesis.

PMID- 8746122
TI  - Effects of the weather conditions on mood and behaviour: the role of acupuncture
      points.
AB  - The proposed hypothesis is that the effects of changing weather patterns on mood
      and behaviour are mediated by electrical processes in acupuncture points.
      Atmospheric electricity affects the state of acupuncture points. This change
      causes alterations in the functioning of neurotransmitters in the central nervous
      system, which leads to a shift in the psychological condition. Electroacupuncture
      can be a means to treat, or to prevent the negative influences of unsettling
      weather conditions.

PMID- 8746123
TI  - Nitric oxide and cancer.
AB  - The possibility that the overall process of carcinogenesis may be linked to the
      deficiency of nitric oxide in a biological cell is examined. A hypothetical model
      of how this might operate to produce subtle changes in a cell resulting in and/or
      facilitating carcinogenesis is suggested.

PMID- 8746124
TI  - Successful cancer therapy with promethazine: the rationale.
AB  - Evidence supporting the claim that specific phenothiazines, notably
      chlorpromazine and promethazine, may be used as sole agents for the treatment of
      cancer in man, has been reviewed. Selective destruction of cancerous tissue can
      be achieved by modulating energy metabolism in malignant cells. In the light of
      available information, the drug of choice is promethazine, the effects of which
      on the central nervous system are relatively weak. The maintenance of continuous
      pharmacological pressure against malignant growths forms an essential feature of
      the therapy. Protection against blood dyscrasias may be secured through the
      provision of adequate amounts of trace elements necessary for the function of
      enzyme systems which detoxicate active oxygen species. Tumour-cell death may be
      facilitated by nutritional supplements of specific polyunsaturated fatty acids.
      Interference from adventitious medications and drug resistance are discussed;
      appropriate therapy is outlined.

PMID- 8746125
TI  - Two types of cancer cells and cytotoxic therapies.
AB  - As previously described in a series of hypotheses (1-5), cancer tissue consists
      of two types of cancer cells: maturable and non-maturable. Almost all of the
      cancer tissue is composed of the maturable type. However, the rest, even if very
      few in number, consists of the non-maturable type. These non-maturable cells
      contribute to establishment of cancer organoid continuity and are responsible for
      oncogenesis, whereas the maturable cells, while organizing almost all of the
      tissue, gradually mature into end cells and eventually complete their limited
      life-spans without contributing to continuity. During the maturation process to
      the end-cell phase, most cancer cell characteristics can be expressed only by
      maturable cells, not non-maturable cells. Since most cytotoxic cancer therapies
      appear to be designed simply to exploit the cell characteristics expressed only
      in maturable cells, they may only be effective in destroying maturable cells
      which complete their life-span, not the non-maturable cells responsible for
      oncogenesis. Such therapy cannot be regarded as genuine cancer eradication, even
      if it destroys numerous cancer cells, and decreases cancer volume. Therefore,
      instead of the cytotoxic therapy employed up until now, a different concept of
      cancer therapy must be devised in an attempt to achieve genuine cancer
      eradication.

PMID- 8746126
TI  - A mechanism for masking receptors with particular application to asthma.
AB  - This study ensconces the concept currently popular in neurophysiology that nerve
      terminals can be sensitized by 'unmasking' more receptors, but goes on to propose
      that the unknown substance masking the remainder is surface-active phospholipid.
      These molecules are considered to bind reversibly by adsorption to receptor
      surfaces just as they are known to do at a variety of tissue surfaces at which
      they impart 'barrier' properties very similar to those much exploited in the
      physical sciences. This model of nonspecific adsorption is further extended to a
      wide variety of receptors in lung airways including those on smooth muscle, to
      explain the normal control of sensitivity of reflex bronchoconstriction indicated
      by many physiological features. In the corollary hypothesis, asthma is attributed
      to a basic deficiency in surfactant causing undue unmasking of receptors exposed
      to the next noxious stimulus to enter the lungs. This model is shown to be
      compatible with the actions of a very wide variety of sensitizing agents which
      are physical, chemical and biological in nature; while the inflammation arising
      from the more biological routes can be correlated according to whether they
      release surfactant or disrupt it. Special attention is focused upon the diverse
      actions of nonsteroidal anti-inflammatory drugs versus steroids widely prescribed
      for asthma which promote the secretion of surfactant, as do the popular beta
      agonists.

PMID- 8746127
TI  - Deleterious effects of prostaglandin E2 in reflux oesophagitis.
AB  - There is good evidence in the medical literature that nonsteroidal anti
      inflammatory drugs exert salutory effects in animal models of reflux
      oesophagitis. This hypothesis accounts for these observations by describing the
      biochemical mechanism of nonsteroidal anti-inflammatory drugs. Since nonsteroidal
      anti-inflammatory drugs inhibit the synthesis of prostaglandins, it is proposed
      that prostaglandins exert deleterious effects during oesophagitis. This
      hypothesis is supported by clinical observations and can explain several features
      of oesophagitis, especially the relationship between inflammation and
      dysmotility. The controversial implication of this hypothesis is that
      nonsteroidal anti-inflammatory drugs may be useful in the therapy of severe
      oesophagitis.

PMID- 8746128
TI  - The potentiality and practicality of a 'salt-free' diet for the prevention and
      amelioration of human disorders.
AB  - The potential of a salt-free diet, which restricts sodium intake to 10 mmol/day,
      for the prevention and amelioration of human diseases and conditions, may be
      considerable. Several human disorders may be the result of dietary-salt-generated
      high-bodily-sodium motility and fluid retention, this being incompatible with the
      maintenance of bodily homeostasis whenever the body is subjected to stress.
      Equally importantly, the present-day impracticalities of adopting a 'salt-free'
      diet appear man-made, and therefore soluble once a sufficiency of purpose exists.

PMID- 8746129
TI  - Deficient heat shock protein expression: a potential mechanism for the sudden
      infant death syndrome.
AB  - Induction of heat shock proteins follows a metabolic stress and protects from
      subsequent stresses. Stressors proposed for the sudden infant death syndrome
      include infection, environmentally-induced hyperthermia and hypoxia. Failure to
      express heat shock proteins to such stressful conditions may lead to reduced
      tolerance, and enhance inappropriate physiologic responses and vulnerability
      which ultimately may lead to infant death.

PMID- 8746130
TI  - Left-right symmetry and asymmetry.

PMID- 8746131
TI  - Identification of four genomic groups of Borrelia burgdorferi sensu lato in
      Ixodes ricinus ticks collected in a Lyme borreliosis endemic region of northern
      Croatia.
AB  - We investigated the presence of Borrelia burgdorferi sensu lato in Ixodes ricinus
      ticks collected in a Lyme borreliosis (LB) endemic region of northern Croatia.
      Ticks (n = 124) were collected at five locations and analysed by the polymerase
      chain reaction (PCR). A DNA fragment from the internal transcribed spacer (ITS2)
      of I. ricinus was detected in all tick lysates, indicating that PCR inhibitors
      were not present. Borrelia burgdorferi sensu lato DNA was detected in 56 out of
      124 ticks (45%). Four genomic groups were identified: Borrelia afzelii (n = 26),
      Borrelia garinii (n = 5), group VS116 (n = 5) and B. burgdorferi sensu stricto (n
      = 1). Mixed infections of B. afzelii with group VS116 (n = 10) and B. afzelii
      with B. burgdorferi sensu stricto (n = 1) were also detected. Eight ticks
      contained B. burgdorferi sensu lato, which could not be typed. The detection of
      B. afzelii and B. garinii in ticks was in agreement with manifestations of LB
      found locally. The occurrence of group VS116 in northern Croatia and in an
      earlier study in The Netherlands, infers that this genomic group may be well
      established in European I. ricinus.

PMID- 8746132
TI  - Efficacy of pheromone-acaricide-impregnated tail-tag decoys for controlling the
      bont tick, Amblyomma hebraeum (Acari: Ixodidae), on cattle in Zimbabwe.
AB  - A large-scale field test using pheromone-acaricide-impregnated plastic tail-tag
      decoys demonstrated excellent efficacy of these devices for control of the bont
      tick, Amblyomma hebraeum, on cattle in Zimbabwe. The tail tags were impregnated
      with a mixture containing o-nitrophenol, methyl salicylate, 2,6-dichlorophenol
      and phenylacetaldehyde and one of three different acaricides (cyfluthrin,
      flumethrin or alphacypermethrin). o-Nitrophenol and methyl salicylate are
      components of the A. hebraeum attraction-aggregation-attachment pheromone, while
      2,6-dichlorophenol and phenylacetaldehyde are proven attractants for this tick.
      Both o-nitrophenol and methyl salicylate were lost gradually from the tags over
      12 and 14 week periods, respectively. In field trials, tick counts were compared
      between cattle that received tail tags either impregnated with pheromone mixture
      alone, cyfluthrin and pheromone mixture, flumethrin and pheromone mixture,
      alphacypermethrin and pheromone mixture or were left untreated. During the first
      3 month trial period, control of adult bont ticks was 94.9% with cyfluthrin tail
      tags and 87.5% with flumethrin tail tags. In general, there was no significant
      difference in bont tick numbers on cattle without tags and those with tail tags
      containing pheromone only. When the trial was repeated for another 3 month
      period, control of bont ticks with tail tags containing cyfluthrin and flumethrin
      was 99.3 and 95.1%, respectively. However, control of bont ticks using
      alphacypermethrin was only 79.2%. Overall, retention of tail tags was excellent
      although some loss was encountered during the rainy season. In addition to
      controlling bont ticks, the tail tags provided moderate control of other tick
      species (Rhipicephalus evertsi evertsi, Rhipicephalus zambeziensis and Hyalomma
      spp.) simultaneously infesting cattle in the trials.

PMID- 8746134
TI  - Clinical dental auxiliary training.

PMID- 8746133
TI  - The seasonal occurrence of ticks (Acari: Ixodidae) on sheep and in the field in
      the Judean area of Israel.
AB  - A 2 year survey of ixodid ticks in the Judean area of Israel between 1983 and
      1985 showed that sheep were parasitized by the following species: Rhipicephalus
      sanguineus group (30.6%), Rhipicephalus bursa (25.3%), Haemaphysalis cretica
      (20.5%), Haemaphysalis otophila (20.1%) and Hyalomma anatolicum excavatum (3.1%).
      Three other species, Hyalomma marginatum rufipes, Boophilus annulatus and
      Amblyomma lepidum were also present but in very low numbers. A total of 50,816
      specimens (78.1% adult ticks) were collected from the sheep. In the field, a
      total of 4780 ticks (8.7% adults) were collected and 64.3% consisted of R. bursa.
      Other species found were H. cretica (14.5%), H. a. excavatum (13.7%), H. otophila
      (3.4%), R. sanguineus group (1.9%) and 1.7% was Ixodes eldaricus. The number of
      ticks collected varied from year to year and seasonal activity was observed in
      all species except for H. a. excavatum. In all species, males outnumbered
      females, with the exception of H. cretica. The seasonal occurrence, tick ecology
      and disease relationship is discussed for each species.

PMID- 8746135
TI  - Private practice: salvation or nemesis for the dental profession?

PMID- 8746136
TI  - MRI update: the effect of dentist attire on patient perceptions of skill, caring
      and professionalism.
AB  - We are trained from our earliest years to draw significance from colour and
      dress. Thus, whilst Cinderella shyly appears in a sparkling white gown, the
      wicked stepmother flaunts in purple and black; in the same way we come to expect
      doctors to wear a white coat. But does what doctors and dentists wear really
      affect patient perceptions of the professionalism of the service and quality of
      care received? The results of a recent study by Martin Fallowfield, a GDP in
      Peterborough, will soon uncover the facts. Dentists can then know whether what
      they wear affects their patients' perceptions of the service they provide.

PMID- 8746137
TI  - Sedation in general practice.

PMID- 8746138
TI  - Whitening toothpastes.

PMID- 8746139
TI  - School screening.

PMID- 8746140
TI  - Oral disease.

PMID- 8746141
TI  - An investigation into the standard of orthodontic treatment carried out by GDPs
      after completion of a clinical assistant training.
AB  - A sample of 172 orthodontic patients treated by 10 general dental practitioners
      in their practices was assessed in terms of treatment need and standard of
      treatment provided. The practitioners had been clinical assistants, for a minimum
      of 2 years, at a District General Hospital before starting any of the cases.
      Prior to treatment 70% of the cases had a 'clear need' for treatment on dental
      health grounds and 73% of the cases had a 'moderate' or 'great need' for
      treatment on aesthetic grounds. Using the Peer Assessment Rating nomogram to
      assess the treatment standard, 83% of patients could be classed as 'improved' or
      'greatly improved' with treatment but 17% were 'worse or no different'. The
      standard of treatment produced by fixed appliances was found to be superior to
      that produced by removable appliances alone. When removable appliances were used
      the best results were obtained when consultant advice was given. The results for
      the clinical assistant sample are compared with the results for the GDS sample
      published in 1993. Ways of further improving the treatment standards produced by
      the general dental practitioners are considered.

PMID- 8746142
TI  - The acidogenic potential of herbal baby drinks.
AB  - The acidogenic potential of a range of commonly available herbal baby drinks was
      assessed on the basis of their ability to depress plaque pH in vivo in 10 adult
      volunteers using the plaque harvesting technique. In addition the pH and inherent
      acidity of each drink was also analysed in vitro. Solutions of 10% sucrose was
      used as a positive control and full fat milk served as a negative control as it
      has traditionally been recommended as a safe drink. Three of the six test drinks
      had a low pH though most had a low titratable acidity. All drinks, except herbal
      tea, on rising led to a significant drop in the plaque pH to near critical pH
      value of 5.5. Most drinks were also more acidogenic than milk and some behaved
      essentially similar to a 10% sucrose solution. The area under the curve below the
      resting pH was highest for apple and raspberry herbal drink (20.51 +/- 3.66) and
      was the least for herbal tea (0.00) compared with the 10% sucrose control (22.01
      +/- 2.87) and milk (0.07 +/- 0.14). It was concluded that most herbal drinks
      tested, especially those with added fruit, can lead to a significant acid
      production in the plaque and therefore have a potential to cause demineralisation
      of the enamel.

PMID- 8746143
TI  - Fissure sealants: a 4-year clinical trial comparing an experimental glass
      polyalkenoate cement with a bis glycidyl methacrylate resin used as fissure
      sealants.
AB  - The 4-year results of a fissure sealant trial are reported. Glass polyalkenoate
      and bis GMA sealant were applied to 590 first permanent molar teeth using a half
      mouth study design in a group of 228 6-8-year-old children. Similar cariostasis
      was observed for the two materials at the end of 4 years despite marked
      differences in retention. Polyalkenoate cements probably should be regarded as
      'fluoride depot' materials rather than fissure sealants when used in this
      context.

PMID- 8746144
TI  - Centenary year of scientific papers in the British Dental Journal.

PMID- 8746145
TI  - Dental prescribing: minimising the cost to the patient and the NHS.
AB  - The high cost of prescription charges, changes in drug availability and the
      increase in private and independent dental practice means that NHS prescriptions
      may not be the cheapest or most appropriate way of providing drugs to patients.
      This article examines this complex area and provides some practical advice.

PMID- 8746146
TI  - Dental health services research: what is it and does it matter?
AB  - Dentists working in the National Health Service offer an efficient service.
      However, changes in medical and dental technologies require all of us to monitor
      the effectiveness of both established and new treatments. Our clinical practices
      should become 'research laboratories' and we must grasp this opportunity to keep
      dentistry at the forefront of investigations into clinical care.

PMID- 8746147
TI  - Cultural-societal roots of violence. The examples of genocidal violence and of
      contemporary youth violence in the United States.
AB  - Widespread violence in a society must have its origins in cultural
      characteristics, current societal conditions, or both. In this article, the
      cultural, societal, and psychological origins of two very different forms of
      violence are examined. A conception of the origins of genocide and mass killing
      is briefly presented, with the Holocaust and the violence in the former
      Yugoslavia as supporting evidence. Difficult life conditions give rise to
      scapegoating, destructive ideologies, and the evolution of increasing violence
      against a designated enemy. Cultural characteristics that make this process more
      or less probable are described. This is followed by a presentation of the
      socialization experiences of children that generate youth violence. To explain
      the increase in youth violence, the presence of difficult life conditions in the
      United States is noted (due primarily to substantial social change). The effects
      of difficult life conditions, cultural characteristics, and social conditions
      such as poverty and discrimination against minority groups on family life and
      parenting are described. Similarities and differences in the origins of the two
      forms of violence are examined. The role of unfulfilled or frustrated basic human
      needs in generating violence is stressed, and conditions and actions required to
      reduce violence are proposed.

PMID- 8746148
TI  - Basic behavioral science research for mental health. Perception, attention,
      learning, and memory. Basic Behavioral Science Task Force of the National
      Advisory Mental Health Council.

PMID- 8746149
TI  - Human response to environmental noise. Psychological research and public policy.
AB  - A research-based, policy-directed argument is made for increasing psychologists'
      involvement in environmental noise research. Federal policy problems are related
      to the government's reliance on limited data from a dose-response model and the
      neglect of key psychological issues such as individual differences in reactions
      to environmental noise, the psychological factors that mediate annoyance and that
      identify subgroups that may need protection from stress-related health effects,
      and the relationship of perceived control to public response. Problems that have
      limited the usefulness of the empirical base for understanding the psychological
      mediation of noise effects are reviewed. Research applications of psychological
      stress theory and noise appraisal models are discussed as essential both to fill
      in gaps in the literature and to move empirical inquiry in a direction that can
      inform public policy.

PMID- 8746159
TI  - Elephantiasis nostras verrucosa.

PMID- 8746160
TI  - ECG of the month: nomen dubium.

PMID- 8746161
TI  - Zenker's diverticula.
AB  - Zenker's diverticula, or hypopharyngeal diverticula, have a multifactorial
      etiology including both mechanical and structural factors. The diagnosis of the
      diverticula is based on an accurate history and physical examination and is
      confirmed with contrast radiography. Historically, the management of Zenker's
      diverticula has been controversial. Nonetheless, if the patient is symptomatic,
      surgical management is indicated. Surgical procedures include cricopharyngeal
      myotomy, diverticulopexy, diverticulum resection, and endoscopic diathermy (the
      Dohlman procedure). Each has its proponents and each has its disadvantages and
      complication rates. The decision as to which procedure to use hinges on clinical
      factors such as the patient's age, general state of health, and whether or not
      the lesion is recurrent. The pathophysiology of Zenker's diverticula is discussed
      with special reference to the anatomy of the hypopharynx. The evaluation of these
      patients is reviewed, as are some of the current surgical approaches employed
      when treating Zenker's diverticula.

PMID- 8746162
TI  - Lupus aortitis: a case report and review of the literature.
AB  - Systemic lupus erythematosus is a complex immunological and rheumatological
      disease that has numerous complications. Central to the pathogenesis of systemic
      lupus erythematosus is immune complex formation and deposition in blood vessels
      and end organs. This is a case report of an autopsy of a patient with systemic
      lupus erythematosus, end stage renal disease, peripheral vascular occlusive
      disease, pancreatitis, and aortitis. The aortitis was found to be immune complex
      mediated with deposition of IgG, C3, as well as fibrinogen in the wall of the
      aorta as shown by immunofluorescence. The hypercoagulable state of the patient is
      discussed with particular emphasis on the role of anticardiolipin antibodies,
      antiphospholipid antibodies, and anti-beta-2-glycoprotein I in the pathogenesis.
      This case is unique in that the immune complex mediated aortitis has not been
      described in the literature over the past 25 years. We recommend that the
      diagnosis of immune complex mediated aortitis be considered in the differential
      diagnosis of aortitis, particularly in the background of a patient with systemic
      lupus erythematosus.

PMID- 8746163
TI  - February 1846 and 1896.

PMID- 8746164
TI  - Just spending in the face of concentrated need.
AB  - Recent medical innovations have successfully treated many acute ailments, but one
      side effect has been the resulting concentration of chronic illness, and thus
      health care expenditures, among patients who are now living longer. Health care
      analysts, searching for savings, often propose rationing for such expensive
      patients, whose needs threaten to overwhelm the system. Yet, targeting the
      elderly is simply not just. This paper offers both a moral approach to allocating
      scarce health care resources, which respects the rights of the weakest members of
      society without bankrupting society, as well as a critical examination of the
      data regarding concentration of expenses. Spending based on efficacy, in contrast
      with age- or expenditure-based proposals, is both just and consistent with
      financial and medical realities.

PMID- 8746165
TI  - Spinal cord injuries in Louisiana due to falls from deer stands, 1985-1994.
AB  - Serious injuries resulting in paralysis and death have occurred to hunters who
      have fallen from deer stands that were not equipped with safety restraints. Among
      the most serious of these are spinal cord injuries. We examined all deer stand
      related spinal cord injuries reported to Louisiana's Spinal Cord Injuries
      Registry from 1985 through 1994. During the 1985 through 1991 hunting seasons, we
      received reports of 28 deer stand falls resulting in permanent paralysis (an
      average of four each year) and 13 reports of temporary neurologic deficit. These
      injuries led to first-year medical care charges estimated at more than $4.2
      million. None of the patients in the reported cases were using a safety restraint
      at the time of injury. After a public information campaign to make hunters aware
      of the risk of using deer stands without safety belts was conducted in 1992,
      there were no reported spinal cord injuries associated with deer stand falls for
      the following three years.

PMID- 8746166
TI  - Granulocyte labelling kit BW 250/183--results of the European multicenter trial.
AB  - In 6 European countries a multicenter trial with the technetium-99m labelled
      monoclonal anti-granulocyte antibody BW 250/183 was conducted in 775 patients.
      The antibody is used for the immunoscintigraphic visualisation of accumulations
      of granulocytes. The present study was restricted on the investigation of
      patients having inflammations, essentially of the peripheral skeleton (mostly of
      the lower extremities), spinal column, the bowel, or had fever of unknown
      etiology. The overall sensitivity of the method was 83%, and specificity was of
      the same order of magnitude (82%). The procedure yielded additional information
      in 67% of the cases and the treatment strategy was influenced in 35% of the cases
      to positive effect, even though all conventional methods had previously been
      exhausted. Human anti mouse-IgG antibodies (HAMA) were detectable only in about
      4% of patients investigated for the first time.

PMID- 8746167
TI  - Separation of autonomous function from cell density in non-immunogenic
      hyperthyroidism--II. quantified comparison before and after radioiodine therapy.
AB  - Regional autonomous cell mass (Q: cell density ratio) and function (T: toxicity
      index) were compared by double isotope parametric thyroid scintigraphy (Als et
      al., Nucl. Med. 1995; 34) in 53 patients with non-immunogenic hyperthyroidism
      before and after radioiodine therapy (aRIT) and showed a break-down (medians) of
      Q: 4.3-->1.0 (toxic adenomas: TA), 2-->1.1 (multifocal functional autonomies:
      MFA)(p < 0.0001) as of T: 96-->1.7 (TA), 15-->1.1 (MFA) (p < 0.001). Five
      functional aRIT patterns resulted: euthyroidism (n = 37, 70%), at half with
      scarred/non-scarred autonomous areas (low/higher T, respectively), primary
      hypothyroidism (n = 4), residual hyperthyroidism (n = 7), secondary
      hyperthyroidism (n = 5). The last two groups with persistent subnormal TSH values
      were clearly separated by divergent T, thyroxine and triiodothyronine levels. A
      resulting T > 1 may represent a clinically sub-critical mass of residual
      autonomous tissue. This new technique facilitates individual pretherapeutic
      evaluations and aRIT quality control.

PMID- 8746168
TI  - Quantitative whole body scintigraphy--a simplified approach.
AB  - In this paper we present investigations on a simplified method of quantitative
      whole body scintigraphy by using a dual head LFOV-gamma camera and a calibration
      algorithm without the need of additional attenuation or scatter correction.
      Validation of this approach to the anthropomorphic phantom as well as in patient
      studies showed a high accuracy concerning quantification of whole body activity
      (102.8% and 97.72%, resp.), by contrast organ activities were recovered with an
      error range up to 12%. The described method can be easily performed using
      commercially available software packages and is recommendable especially for
      quantitative whole body scintigraphy in a clinical setting.

PMID- 8746169
TI  - [67Ga scintigraphy in retroperitoneal fibrosis (RPF): indications, application
      and clinical relevance--report of five patients].
AB  - AIM: The aim of the study was to evaluate the indication for 67Ga-citrate imaging
      and its clinical impact on patients with retroperitoneal fibrosis (RPF). METHOD:
      The scanning with ventral and dorsal projections was done 48 an 72 h after i.v.
      injection of 370 Mbq 67Ga-citrate. RESULTS: In the 5 patients with idiopathic RPF
      included in the study, there was a remarkably high correlation between the
      clinical symptoms, the surgical and histologic findings, the activity of the
      disease and the results of 67Ga-scintigraphy. CONCLUSION: While CT and--maybe
      even better--MRI might perfectly show the extension, shape and contour of the
      fibrotic tissue, Gallium-67 scan appears to be superior in assessing the
      intensity and activity of the disease process.

PMID- 8746170
TI  - [Conventional nuclear medical diagnosis in the after care of heart
      transplantation].
AB  - Actually more than 80% of heart recipients survive the first postoperative year.
      Early death is mainly caused by rejection and acute infection. After the first
      year progressive graft atherosclerosis has the greatest impact on prognosis. The
      review presents scintigraphic methods that have reached clinical impact in the
      diagnosis of rejection and vascular complications. Immunoscintigraphy with 111In
      labelled monoclonal antibodies against myosin proved to be of importance in the
      diagnosis of rejection especially in long-term follow-up. Perfusion scintigraphy
      reveals vital and ischemic myocardium. In heart transplant recipients
      radionuclide ventriculography has been widely replaced by echocardiography. Up to
      now, the evaluation of increasing nerval integration with 123I-MIBG has not
      reached clinical impact.

PMID- 8746171
TI  - [Diagnosis of recurrence of a glomus carotid artery tumor by somatostatin
      receptor scintigraphy].
AB  - Glomus caroticum tumours belong to the non chromaffine paragangliomas. As the
      incidence is very poor with 1% in the collective of a vascular-surgery
      department, the correct diagnosis is preoperatively only found in 10-20% of the
      cases. The early detection of primary- or recurrence-tumour is important for the
      surgical proceedings. With advanced tumour-stage, i.e. with involvement of the
      carotid artery in the tumour-process, the perioperative mortality increases.
      Furthermore nerve lesions following surgical tumour-resection as a complication
      are more frequent. This case-report point out the importance of the somatostatin
      receptor-scintigraphy in the differentiation of glomus caroticum tumour
      recurrence and postoperative scar. In our patient the suspicion of tumour
      recurrence came up already 2 years ago, but could not be verified by MRT and
      angiography.

PMID- 8746172
TI  - Growth and type-II collagen expression in the glenoid fossa of the
      temporomandibular joint during altered loading: a study in the rat.
AB  - The aim of this study was to measure changes in growth of the glenoid fossa and
      its articular eminence after decreased loading. A further aim was to evaluate the
      role of mechanical forces in relation to the existence of a cartilage layer, by
      determining type-II collagen secretion. A total of 99 Wistar rats were used: 48
      animals were fed whole pellets and 51 were fed ground pellets. At age 21 days,
      after weaning, the upper and lower incisors of the soft-diet group were shortened
      by cutting them, twice a week. Ten animals fed whole pellets and 10 fed ground
      pellets were injected i. p. with Alizarin red (200 mg/kg) at ages 22, 30 and 40
      days, and killed at ages 30, 40 and 50 days respectively. The heads were freed
      from the soft tissue and the zygomatic process cut sagittally at the deepest
      point of the greatest transversal concavity of the eminence. Bone apposition was
      measured. The other animals were used for studies involving collagen II
      immunostaining. Bone growth decreased in the group fed ground pellets except in
      the anterior-most part of the glenoid fossa at 50 days. Immunohistochemical
      analysis revealed larger areas of anti-collagen II staining in the group fed
      whole pellets, most markedly in the posterior part of the glenoid fossa. Growth
      of the articulationg surface of the temporal component of the temporomandibular
      joint appears to depend on mechanical factors, such as the condyle. The
      underlying mechanics seem likely to be different. The presence of type-II
      collagen is obviously not regulated only by compressive forces but probably also
      by tension loading.

PMID- 8746173
TI  - The hyaline zone and associated root surface changes in experimental orthodontics
      in rats: a light and scanning electron microscope study.
AB  - Light and scanning electron microscopic (SEM) examinations were used to study the
      hyaline zone and associated root resorption after orthodontic treatment of the
      upper first molars of rats. The orthodontic treatment consisted of a fixed buccal
      expansion appliance with an initial force of 250 mN. The animals were divided
      into nine experimental groups with orthodontic treatment and one control group
      without orthodontic treatment. Three groups were sacrificed immediately after 1,
      3, and 7 days of treatment, and six groups after 7 days of treatment followed by
      1, 2, 3, 4, 5, and 6 weeks without treatment. A hyaline zone on the pressure side
      of the mesial root was identified at the light microscopic level of examination
      as well as the SEM examination as early as 1 day after the initiation of
      treatment. In the SEM it was found that on the roots of teeth studied in the
      first few days after initiation of treatment the hyaline tissue was so firmly
      attached to the root that it remained in place during the extraction and
      preparation procedures. After longer treatment periods these hyaline zones were
      lost at extraction or during the preparation for the SEM examination. The
      cementum surface under the hyaline zone had a smooth appearance suggesting that
      the surface had been modified by substances released from the hyaline zone. After
      1 week of treatment, resorption in the cementum could be noticed. The resorption
      extended to the dentine as uncovered dentinal tubuli were found. Formation of
      reparative cementum started two weeks after treatment. Changes in the cementum
      surface as well as root resorption cavities could be seen for as long as 6 weeks
      after the cessation of orthodontic treatment.

PMID- 8746174
TI  - Effects of continuous and intermittent forces on human fibroblasts in vitro.
AB  - Orthodontics is based upon the cellular response to biomechanical forces.
      However, little is known about the way cells respond to such forces. An
      experimental model has been designed to study the morphological and metabolic
      behaviour of human cells, subjected to cyclical or static mechanical loads. The
      model involves attaching human fibroblasts to silicone collagen-coated membranes,
      which are subjected to either continuous of cyclical stretching by a motor
      coupled with a movable supporting frame. The effect of continuous or cyclical
      stretching on the secretion of collagenase, an enzyme thought to play an
      important role in the process of tooth movement, was measured. Cyclical
      stretching of fibroblasts over a 4-day period, approximately doubled collagenase
      production as compared with the control. Continuous stretching, on the other
      hand, was only 50 per cent as effective in enhancing enzyme release. In contrast,
      the secretion of the collagenase inhibitor was unaffected by either form of
      mechanical deformation. To understand the effect of cyclical forces further, a
      morphological study using humane fibroblasts was performed. It was found that
      stretching or compression delivered an immediate and proportional deformation of
      the cells. After 10-15 minutes the morphology of cells readapted to the new
      mechanical environment, causing a loss of the biological activation. This suggest
      that a new mechanical stimulus is necessary to induce a new biological reaction.

PMID- 8746175
TI  - Significance of the cant of the posterior occlusal plane in class II division 1
      malocclusions.
AB  - In studying a group of fifty adult females with Class II division 1 malocclusion,
      it was evident that the skeletal problems of this malocclusion involved small,
      retruded mandibles accompanied by backward rotation. This skeletal pattern was
      considered to be influenced by the vertical dimension of the upper dentition in
      the buccal segment for mandibular function. The anterior and the posterior
      occlusal planes were examined to gain a detailed assessment of the relationship
      between the dental and the skeletal patterns. The findings indicated that the
      steep cant of the posterior occlusal plane was strongly correlated with the
      following: 1. Small, retruded mandible with backward rotation as the skeletal
      pattern. 2. Short vertical height of the upper second molars and distal
      inclination of the upper molars as the dental pattern. The increased vertical
      height of the lower second premolars was found to be related to backward rotation
      of mandible. In treating skeletal Class II malocclusions, this study indicated
      that control of the vertical dimension of the posterior teeth is extremely
      important.

PMID- 8746176
TI  - The use of tensor analysis to investigate facial changes in treated class II
      division 1 malocclusions.
AB  - This retrospective cephalometric study examined the facial changes brought about
      by treatment in 62 Class II division 1 children, using tensor analysis. Thirty
      two children were treated with Frankel appliances, whilst the remaining thirty
      received premolar extractions, headgear, and conventional Edgewise mechanics.
      Each child was matched for age and sex with an untreated individual in whom the
      occlusion was deemed satisfactory and the treatment changes were compared with
      those expected during normal development. Results indicated that vertical facial
      development predominated in both treated groups: this exceeded the increase
      expected in an untreated population . The Frankel group exhibited the greater
      gain in lower face height, with changes confined almost entirely to the mandible.
      Effective mandibular position improved but there was no increase in body length.
      The incisors were more favourably positioned within the face with similar
      improvements in the soft tissues. Thus, although facial balance was better
      following a non-extraction Frankel approach, control of the vertical dimension
      was inadequate. The fixed appliance group exhibited a smaller increase in lower
      facial height and no favourable mandibular development: maxillary retraction was
      the most striking skeletal alteration. By removing the traditional, fixed,
      superimpositional framework of the cranial base, tensor analysis highlights
      vertical and mandibular changes not easily detected by conventional cephalometry.

PMID- 8746177
TI  - Orthodontics for the handicapped child.
AB  - The broad spectrum of difficulties that exist in providing orthodontic treatment
      for handicapped children is well known and few practitioners offer such a
      service. The present article offers an analysis of the problems involved and
      provides some practical answers designed to overcome them. It describes some of
      the newer modalities that have become available to the dental profession over the
      last few years and shows how advantage may be gained by their exploitation, in
      orthodontic treatment. Additionally, some of the older and largely-forgotten
      methods, appropriately modified and updated, are represented in this context,
      where they find particular relevance. Guidelines are given to enable the
      orthodontic profession to gain therapeutic access to a section of the population
      that urgently requires treatment.

PMID- 8746178
TI  - Force magnitude applied by orthodontists. An inter- and intra-individual study.
AB  - The aim of this investigation was to study the magnitude and variation of forces
      routinely applied by different orthodontists for buccal tipping of premolars and
      canines in the maxilla, and also to compare these forces with the individually
      considered ideal force. Nineteen clinically experienced orthodontists were asked
      to bend and activate sectional arch wires on a plastic model with bands on the
      first molars. Round 0.016 Australian wires were used on one side and square 0.016
      x 0.016 Blue Elgiloy wires on the other. The tests were repeated a second time 3
      4 weeks later. The applied mean force magnitude was 48.4 cN (g) for premolars and
      40.0 cN for canines, with a considerable intra-individual variation (range 25-75
      cN, and 21-62 cN) using the round Australian wire. In general, the activation of
      the square wire resulted in a higher force, mean difference 29 per cent (11.4 cN)
      for canines and 23 per cent (11.1 cN) for premolars when compared with the round
      wire. On each side, the shorter wire for premolars was activated with a higher
      force when compared with the longer canine wire, mean 16 per cent (8.0 cN) for
      the square wire and 21 per cent (8. cN) for the round wire. Sex, age and clinical
      experience had no major influence on the applied force magnitude. On average, the
      orthodontists considered an ideal force for tipping of canines and premolars to
      be mean 62.5 cN (range 30-100 cN) and mean 56.1 cN (range 30-100 cN)
      respectively. They also reported that a strain gauge was not often used in
      everyday clinical practice. This study showed substantial differences between
      applied forces and considered ideal forces. It is suggested that regular checks
      of the force magnitude should be performed in situations where a certain force is
      considered important.

PMID- 8746179
TI  - Consistency of orthodontic extraction decisions.
AB  - Ten orthodontists having completed specialist training, examined on two occasions
      1 month apart, the complete pre-treatment records of 60 Class II division 1
      patients representing the full range of dental malocclusion severity. At each
      session the orthodontist recorded whether their proposed treatment involved
      extractions. The level of agreement both between and within the orthodontists was
      evaluated with the Kappa statistic. Data analysis revealed that the level of
      agreement within the examiners was good, however the between examiner agreement
      was poor. It appeared that the orthodontists were applying different criteria in
      terms of the extraction decision and this has implications for orthodontic
      patients.

PMID- 8746180
TI  - Enamel fluoride levels after orthodontic band cementation with glass ionomer
      cement.
AB  - The aim of this investigation was to examine the fluoride uptake by enamel after
      application of glass ionomer cement for orthodontic band cementation compared
      with zinc phosphate cement. The study was conducted on 21 children whose mean age
      was 14 years. All the children were reared in the Middle Anatolian cities where
      the water fluoride concentration was below the level of 0.50 ppm. The subjects
      were randomly divided into three groups. The first experimental group, had seven
      subjects whose teeth were topically fluoridated with 2 per cent NaF solution,
      before orthodontic band cementation with zinc phosphate cement. The second
      experimental group also had seven subjects whose orthodontic bands were cemented
      with glass ionomer cement. The third group, consisted of seven control subjects
      and no dental procedures were performed in this group. All the participants were
      followed for 3 months and at the end of this period maxillary first premolars,
      which were in the ninth developmental stage according to Nolla (1960), were
      extracted for orthodontic purposes. The enamel fluoride concentrations were
      determined on the left maxillary first premolars at three successive etch depths
      by means of a fluor ion electrode, whereas the calcium concentrations were
      determined with an atomic absorption spectrophotometer. The results of this
      investigation showed that in both cementation groups enamel fluoride
      concentrations at three successive etch depths were highly increased compared
      with the control group. However, the difference between the cementation groups
      was not statistically significant.

PMID- 8746181
TI  - Comparative shear bond strength of some orthodontic bonding resins to enamel.
AB  - The aim of this study was to compare the in vitro bond strength, to bovine enamel
      measured in shear, of the orthodontic adhesives Lee Insta-bond (LiB), Rely-a-Bond
      (RaB), Right-on (Ro), Concise precoating method (Cc), Concise mixed method (CaB),
      Super-C (Sc), and Orthon (Or), and of the glass ionomer cement Ketac-Cem (KC).
      The fracture surfaces after debonding were also examined in order to determine
      the sites of failure. The results indicate that there is a significant difference
      between the shear bond strength obtained with the different adhesives so that the
      mean shear bond strength decreases in the order [Ro approximately Cab
      approximately Sc] > [LiB approximately RaB approximately Cc] > Or > KC. Moreover,
      for Cab and Sc it was found that the shear bond strength varies depending on the
      location on the bovine tooth. The failure site was essentially at the resin
      bracket interface, except for Concise, where only 50 per cent of the cases failed
      at the resin-bracket interface.

PMID- 8746182
TI  - Study of an enzyme coupled system for the development of fibre optical bilirubin
      sensors.
AB  - We have established an analytical procedure for bilirubin (BR) determination by
      following the variation of its yellow absorption band in the presence of the
      biocatalytic system haemoglobin/glucose oxidase/glucose. The influence of the pH
      of the medium, the haemoglobin/hydrogen peroxide ratio, and the concentration of
      the various components in the mixture on the system activity was evaluated. The
      solubility of the unconjugated BR was analysed. An anionic detergent in Tris
      buffer, in which it presents a high critical micellar concentration, was selected
      for the BR/bovine serum albumin cleavage. The Michaelis-Menten constant of the
      system (after the optimisation of the various parameters) was determined and
      compared with Km values reported in the literature for similar catalytic systems.
      Preliminary results obtained with the haemoglobin and glucose oxidase immobilised
      either in poly(vinyl alcohol) or by crosslinking with glutaraldehyde, show that
      this system is promising as a future biosensor.

PMID- 8746183
TI  - Enzymatic membranes for determination of some disaccharides by means of an oxygen
      electrode.
AB  - Membranes for determination of maltose, lactose and sucrose with the use of an
      oxygen electrode are described. They were obtained by immobilization of glucose
      oxidase with suitable disaccharide hydrolase in gelatin or albumin. For the
      sucrose determination mutarotase was also used. The membranes contained one, two
      or three enzymes working in sequence. The enzyme composition of the membranes
      influenced the linear range slightly and the value of electrode response
      considerably. The electrode response of the maltose membranes was also affected
      by the immobilization material. The measurements with the use of enzymatic
      membranes were very sensitive to temperature and, to some degree, the pH of the
      sample. Stability of the membranes was differentiated. The albumin membranes for
      sucrose determination generated almost the same signal after 1 month of frequent
      use, whereas the gelatin membranes for lactose determination lost about 85% of
      the initial activity after 1 week of operation. The electrode response of both
      the gelatin and albumin maltose membranes decreased in the same time by about
      50%.

PMID- 8746184
TI  - Covalently immobilized enzymes on biocompatible polymers for amperometric sensor
      applications.
AB  - Glucose oxidase or choline oxidase were covalently immobilized on the surface of
      2-hydroxyethyl and glycidyl methacrylate copolymer membranes. The polymerization
      was induced by gamma irradiation at low temperature. The enzyme modified polymers
      were applied on Clark-type or platinum electrodes to form amperometric sensors
      based on the electrochemical measurements of oxygen or hydrogen peroxide. Glucose
      and choline content in standard solutions were measured and linear calibration
      curves were determined. The sensors studied showed a response time of less than 2
      min and the observed linear ranges were increased with respect to usual
      biosensors owing to the diffusion-limiting effects of the membranes used. The
      influence of the copolymer composition on the electrochemical response and on the
      retained enzyme activity were explored for verifying the optimum analytical
      performance. The immobilized enzyme membranes stored in suitable buffers were
      very stable and showed a decrease up to 20% in the electrode response after 3
      months of constant use.

PMID- 8746185
TI  - Surface plasmon resonance studies of immunoreactions utilizing disposable
      diffraction gratings.
AB  - The specificity of protein binding between immuno-gamma globulin (IgG) and anti
      IgG has been investigated by means of surface plasmon resonance measurements,
      with a view to determining whether a perspex replica of a holographic diffraction
      grating can be used efficiently as the momentum-coupling device. The replicas are
      easy to fabricate, of low cost, and may be useful as disposable sensing heads in
      a biosensor. The majority of all published work concerning surface-plasmon-based
      biosensors has detailed the use of prisms as the momentum-coupling devices.
      Therefore, the relative advantages and disadvantages of both systems are
      discussed in this paper, including a sensitive optical technique which is beyond
      the scope of prism geometries.

PMID- 8746186
TI  - FET-microbial sensor for xylose detection based on Gluconobacter oxydans cells.
AB  - A potentiometric biosensor for xylose was devised utilizing Gluconobacter oxydans
      whole cells. Immobilization methods based on physical adsorption were used for G.
      oxydans cells and extracellular pH changes resulting from xylose dehydrogenation
      were monitored by a field effect transistor (FET). The G. oxydans, FET-based
      sensor detected xylose at a lower limit of 0.5 mM. From 5.0 to 30 mM xylose, the
      response of the sensor was linear. Expectedly, output signals were significantly
      suppressed by buffer (Tris-HCl). Responses were essentially stable for at least
      four weeks of storage and showed only a slight loss of initial xylose
      sensitivity. Xylitol exerted an insignificant influence on the sensor's response
      to xylose. However, the response to glucose was 5 times higher in relation to
      that of xylose at the same concentration (1 mM). For xylose determinations in the
      presence of glucose, a two-step assay is discussed.

PMID- 8746187
TI  - A one-step, separation-free amperometric enzyme immunosensor.
AB  - A new one-step, separation-free, amperometric enzyme immunosensor is described.
      The sensor consists of an antibody electrode that is low cost, disposable, and
      operates without washing or separation steps. The immunosensor combines the
      following signal-amplification systems: enzyme-channeling immunoassay;
      accumulation of the redox mediators (I2/I-); cyclic regeneration of an enzyme
      (peroxidase) substrate at the (polyethylenimine) polymer/electrode interface; and
      control of the hydrodynamic conditions at the interface of the antibody
      electrode. The immunological reactions were monitored electrochemically in situ,
      and the binding curves were directly visualized on a computer screen. The
      complete immunoassay can be performed in 5-20 min depending on the complexity of
      the immunological reactions. Model systems using rabbit IgG and human luteinizing
      hormone (hLH) in a 'sandwich' immunoassay revealed that the immunosensor can
      detect concentrations of hLH in human serum as low as 1 ng ml-1.

PMID- 8746188
TI  - A microdialysis fibre based sampler for flow injection analysis: determination of
      L-lactate in biofluids by an electrochemically synthesised bilayer membrane based
      biosensor.
AB  - A microdialysis fibre based, low volume sampler is described which can be used in
      flow injection analysis (FIA) when an on-line dilution of the sample and/or
      removal of high molecular weight interferents is required. This device used in
      combination with a lactate amperometric biosensor based on lactate oxidase
      electrochemically immobilised in a bilayer membrane of poly(o-phenylendiamine)
      and overoxidized poly(pyrrole) permits the extension of the linear range of
      response up to 10 mM lactate. Combining microdialysis sampling with FIA and
      amperometric detection at an interference-free and fast-response biosensor,
      lactate determination in complex media such as serum, milk and yoghurt can be
      easily achieved with a high sample throughput and no sample pre-treatment.

PMID- 8746189
TI  - A new urea sensor based on combining the surface acoustic wave device with urease
      extracted from green soya bean and its application--determination of urea in
      human urine.
AB  - The urea sensor was prepared by combining a surface acoustic wave (SAW) device,
      in which a SAW resonator operating at 61 MHz and a pair of parallel electrodes
      were used in series, with urease extracted from green soya bean. The Michaelis
      constant and maximum reaction rate of the urease were estimated as 2.14 mM and
      27.18 kHz min-1, respectively, at pH 7.0 and 25.0 degrees C. Influences of pH,
      temperature and effectors on the response properties of the SAW urea sensor were
      investigated. Recovery of the sensor ranged from 95 to 105% and the detection
      limit of urea was 1.0 micrograms ml-1 (1.7 x 10(-5) M). The proposed sensor has
      been successfully applied to the rapid determination of urea in human urine
      samples. The results are consistent with the reported values and also support the
      clinical diagnosis.

PMID- 8746190
TI  - Covalent enzyme immobilization on paramagnetic polyacrolein beads.
AB  - An optimized procedure of covalent glucose oxidase, urease, Bacillus subtilis
      alpha-amylase and Bacillus licheniformis alpha-amylase immobilization on
      paramagnetic, non-porous, polyacrolein beads is presented. The resulting
      insolubilized enzymes can be employed for extended periods of time without loss
      of activity. The conditions were optimized for maximizing the activity of the
      linked enzyme. Coated beads bearing up to 15 micrograms active enzyme/mg(beads)
      were obtained on reproducible basis. The paramagnetic feature of the particles
      facilitates the enzyme handling. In the magnetic field, the enzyme separation is
      fast and complete. Thus, the paramagnetic beads represent an excellent carrier
      for immobilized enzymes.

PMID- 8746191
TI  - The medical management of gastro-oesophageal reflux.

PMID- 8746192
TI  - Management of scalp ringworm.

PMID- 8746193
TI  - Quinine for nocturnal leg cramps?

PMID- 8746194
TI  - Insulin-like growth factor I and its binding proteins in the cardiovascular
      system.
AB  - A large body of evidence has conclusively shown that IGF I is an essential
      regulator of developmental growth. Thus mice bearing a null mutation for the IGF
      IR gene invariably die shortly after birth, and mice bearing a null mutation for
      the IGF I gene have a high neonatal mortality rate and marked growth retardation
      [158,159]. The ubiquitous effects of IGF I make it likely that this
      autocrine/endocrine system plays an important role in cardiovascular development.
      Its potential role in cardiovascular pathophysiology has raised considerable
      interest over the last several years. There is strong evidence that IGF I is a
      critical determinant of vascular growth responses in vitro and in vivo.
      Regulation of VSMC IGF IR availability appears to be crucial for the control of
      VSMC growth, and as such is at a convergence point for the effects of multiple
      growth factors. Clinical studies relating to IGF I in hypertension are extremely
      limited but significant data from animal studies now suggest a role for IGF I as
      a mediator of hypertrophic/hyperplastic responses in hypertension. Furthermore,
      significant animal data now exist implicating IGF I as an important mediator of
      cardiac hypertrophic responses. The development of a specific pharmacologic
      inhibitor of the IGF IR should allow rational clinical trials to address the
      function of IGF I as a mediator of cardiovascular growth responses. Specifically,
      areas of great interest will include the potential prevention of post-angioplasty
      restenosis, of atherosclerotic lesion development and progression, and of the
      complications of hypertensive vascular disease. The use of IGF I to ameliorate
      myocardial growth and function post infarction, to promote angiogenesis and
      collateral artery formation in the setting of peripheral vascular disease, are
      other important directions for future research. The use of IGF I to improve wound
      healing, improve recovery from acute renal failure and improve glucose control is
      currently under investigation. Clearly ongoing studies addressing the mechanisms
      whereby IGF I interacts with its receptor and binding proteins to produce its
      effects in cardiovascular tissues, will provide a rationale for novel and
      pertinent clinical research.

PMID- 8746195
TI  - The lonely failing heart: a case for ECM genes.

PMID- 8746196
TI  - The lonely failing heart: a case for ECM genes.

PMID- 8746197
TI  - Hypoxia activates nitric oxide synthase and stimulates nitric oxide production in
      porcine coronary resistance arteriolar endothelial cells.
AB  - OBJECTIVE: Hypoxia significantly alters vascular tone in coronary resistance
      arterioles during prolonged ischemia, potentially through the modulation of
      endothelial cell metabolism as well as endothelial function. The objective of
      this study was to test the hypothesis that constitutive nitric oxide synthase
      (cNOS) is sensitive to oxygen tension and that hypoxia increases the activity of
      cNOS and nitric oxide production in the porcine coronary microcirculation.
      METHODS: Monocultures of porcine coronary resistance arteriolar endothelial cells
      (RAEC) were isolated and proven to be endothelium based upon morphology, binding
      of acetylated LDL, and factor VIII antigen positivity. Cells were exposed to
      either hypoxia (pO2 = 10 mmHg) or normoxia (pO2 = 160 mmHg) for varying periods
      of time. Nitric oxide production was directly measured using a chemiluminescence
      method, while cNOS enzyme activity was assayed using a fibroblast-report cell
      method. cNOS protein was quantitated by Western blot analysis using the H32
      monoclonal antibody to the endothelial cell constitutive isoform of NOS. RESULTS:
      Hypoxia significantly augmented A23187-stimulated nitric oxide production [23.77
      (1.73) vs 14.94 (0.66) nmol . micrograms-1 protein, hypoxia vs. normoxia
      respectively, n = 8, P < 0.01]. Using the fibroblast reporter cell assay, cNOS
      activity was increased in RAEC after exposure to hypoxia for 30, 120 and 240 min
      [normoxia control: 0.16 (0.04) fmol . microgram-1 protein; hypoxia: 30 min = 1.00
      (0.19), 120 min = 1.08 (0.04), 240 min = 1.26 (0.07) fmol . micrograms-1 protein
      (n = 6, p < 0.01)]. Western blots showed a single band at 135 kDa that was
      increased in homogenates of cells previously exposed to hypoxia. CONCLUSIONS:
      These experiments demonstrated that the regulation of cNOS is sensitive to oxygen
      tension. Hypoxia significantly activated constitutive nitric oxide synthase in
      coronary resistance arteriolar endothelial cells, and this was translated to an
      increased production of nitric oxide.

PMID- 8746198
TI  - Regional alterations of left ventricular contraction and inotropic reserve in
      conscious dogs with heart failure.
AB  - OBJECTIVE: The goal was to examine left ventricular (LV) regional contraction
      alterations and especially, regional inotropic reserve changes in tachycardia
      induced heart failure (HF). METHODS: Eleven dogs were chronically instrumented to
      measure LV pressure and its first time derivative (LV dP/dt), left atrial and
      aortic pressures and to measure antero-apical (AS), -basal (BS) and postero
      apical (PS) subendocardial segmental contractions by ultrasonic crystals.
      Dobutamine (5-15 micrograms/kg per min) and left atrial pacing (150-240
      beats/min) were performed in the control state (C) and in HF induced by chronic
      right ventricular pacing (240 beats/min, 3 weeks). RESULTS: In HF, as compared
      with in C, LV dP/dt max decreased and LV end-diastolic pressure and end-diastolic
      segmental lengths increased (Ps < 0.005). The percentage of systolic shortening
      was more depressed in PS (from 21 +/- 1% to 7 +/- 1%, P < 0.001) than in AS and
      BS (from 24 +/- 1% to 17 +/- 1% and from 20 +/- 2% to 13 +/- 1% respectively, Ps
      < 0.05). During dobutamine infusion, in HF as compared with C, the increases in
      LV dP/dt max were smaller (dobutamine 15 micrograms/kg per min: HF: + 36 +/- 6%
      vs C: + 68 +/- 11%, P < 0.01) and the increases in the systolic shortening of the
      three segments were also smaller. However, the responses of the three segments
      were similar in HF and in C. During left atrial pacing, LV dP/dt max increased
      less in HF than in C and the poststimulation potentiation of LV dP/dt max was
      impaired in HF. However, the responses of the systolic shortening during regular
      left atrial pacing and the increase in the percentage of systolic shortening of
      the first poststimulation beat were similar in all regions. CONCLUSION: In
      tachycardia-induced HF, although LV regional contraction is heterogeneously
      altered, the inotropic reserve appears to be similarly modified in all regions.

PMID- 8746199
TI  - Low concentrations of angiotensin II unmask vasoconstrictory alpha 2
      adrenoceptors in isolated perfused kidneys of spontaneously hypertensive rats.
AB  - OBJECTIVES: The aim of the present study was to evaluate the role of vascular
      alpha 1- and alpha 2-adrenoceptors in kidneys of spontaneously hypertensive rats
      (SHR) and normotensive Wistar Kyoto rats (WKY). METHODS: SHR and WKY kidneys (12
      14 weeks) were isolated and perfused with Krebs-Henseleit solution. Concentration
      response curves for the alpha 1-adrenoceptor agonist methoxamine and the alpha 2
      adrenoceptor agonist UK 14304 were constructed alone and in the presence of the
      alpha 1-adrenoceptor antagonist prazosin, the alpha 2-adrenoceptor antagonist
      idazoxan and exogenous angiotensin II. RESULTS: Methoxamine induced a maximal
      pressor response of 247 +/- 9 mmHg with an EC50 of 1.3 +/- 0.1 microM in SHR and
      of 193 +/- 4 mmHg with an EC50 of 1.1 +/- 0.1 microM in WKY. The concentration
      response curve for methoxamine was shifted to the right by prazosin with a pA2
      value of 9.29 (SHR) and 9.26 (WKY) and by idazoxan with a pA2 value of 6.45 (SHR)
      and 6.33 (WKY). UK 14304 induced a maximal pressor response of 41 +/- 12 mmHg in
      SHR and of 37 +/- 8 mmHg in WKY. Angiotensin II (0.1 nM) did not significantly
      alter pressor responses to methoxamine but caused a marked shift to the left of
      the concentration-response curve for UK 14304. UK 14304 then induced a maximal
      pressor response of 92 +/- 13 mmHg with an EC50 of 0.07 +/- 0.01 microM in SHR
      and of 78 +/- 14 mmHg with an EC50 of 0.14 +/- 0.01 microM in WKY. In the
      presence of angiotensin II (0.1 nM) the concentration-response curve for UK 14304
      was shifted to the right by prazosin with a pKB of 6.36 (SHR) and 6.33 (WKY) and
      by idazoxan with a pKB of 7.68 (SHR) and 7.65 (WKY). CONCLUSIONS: The results
      demonstrate a predominant role of vasoconstrictory alpha 1-adrenoceptors over
      alpha 2-adrenoceptors in SHR and WKY isolated kidneys. Low physiological
      concentrations of angiotensin II unmask functional vascular alpha 2-adrenoceptors
      which are slightly more sensitive in SHR than in WKY kidneys.

PMID- 8746200
TI  - Aspirin does not potentiate effect of suboptimal dose of the thrombin inhibitor
      inogatran during coronary thrombolysis.
AB  - OBJECTIVES: Coronary artery often reoccludes after thrombolytic therapy with
      recombinant tissue-plasminogen activator (rt-PA). This reocclusion is thought to
      be due to in situ platelet activation mediated by thromboxane (Tx) A2 and
      thrombin; hence, aspirin and thrombin inhibitors are often used in patients with
      acute myocardial infarction. This study was designed to examine the modulation of
      coronary artery reocclusion by a novel low molecular weight direct thrombin
      inhibitor inogatran with or without aspirin. METHODS: 22 dogs with electrically
      induced occlusive intracoronary thrombus were treated with saline (n = 7, group
      A), or high dose inogatran (0.25 mg/kg bolus followed by 0.6 mg/kg per h for 2 h,
      n = 5, group B), or low dose inogatran (0.125 mg/kg bolus followed by 0.3 mg/kg
      per h for 2 h, n = 5, group C), or aspirin+low dose inogatran (n = 5, Group D).
      Recombinant tissue-plasminogen activator (rt-PA) was infused for 20 min starting
      2 min after the bolus in all dogs. Coronary artery blood flow was monitored for
      120 min after rt-PA administration. RESULTS: Reperfusion rates were similar in
      all groups, but the time to reperfusion was shortest in group B dogs (18 +/- 2
      min vs. 32 +/- 7 min in group A dogs, P < 0.05). Reocclusion rates were 80%, 0%,
      50%, and 60% in groups A, B, C, and D dogs, respectively. The restored blood flow
      persisted for 19 +/- 10, > 120 min, 71 +/- 30 and 54 +/- 26 min in groups A, B,
      C, and D dogs, respectively. At the end of rt-PA infusion, prothrombin time (PT)
      and activated partial thromboplastin time (APTT) were increased 1.3-2 times the
      control value, and the changes in PT and APTT were similar in all groups.
      Thrombin generation and activity, assessed by rise in thrombin-antithrombin
      complex and fibrinopeptide A levels, and decrease in fibrinogen levels were most
      marked in group A dogs, and less so in group B, C and D dogs. CONCLUSIONS: These
      data show that high dose of direct thrombin inhibitor inogatran shortens time to
      reflow and abolishes coronary artery reocclusion. However, aspirin does not
      potentiate the effect of suboptimal doses of inogatran.

PMID- 8746201
TI  - Acute hypoxic pulmonary vasoconstriction in man is attenuated by type I
      angiotensin II receptor blockade.
AB  - OBJECTIVES: We examined the hypothesis that angiotensin II (ANG II) is a
      modulator of acute hypoxic pulmonary vasoconstriction (HPV) by looking at the
      effect of losartan, a selective type 1 ANG II receptor antagonist, on acute HPV
      in man. METHODS: Ten normal volunteers were studied on two separate days. They
      either received pre-treatment with losartan 25, 50, 100, 100 mg respectively on
      four consecutive days or matched placebo. They were then rendered hypoxaemic, by
      breathing an N2/O2 mixture for 20 min to achieve an SaO2 of 85-90% adjusted for a
      further 20 min to achieve an SaO2 of 75-80%. Pulsed wave Doppler echocardiography
      was used to measure mean pulmonary artery pressure (MPAP), cardiac output and
      hence pulmonary vascular resistance (PVR). RESULTS: Baseline MPAP and PVR (during
      normoxaemia) were unaffected by losartan pre-treatment compared with placebo.
      However, losartan significantly reduced MPAP at both levels of hypoxaemia
      compared with placebo: 14.7 +/- 0.7 vs 19.0 +/- 0.7 mmHg at an SaO2 85-90% (P <
      0.01) and 20.0 +/- 0.7 vs 25.7 +/- 0.8 mmHg at an SaO2 75-80% (P < 0.05)
      respectively. Similarly losartan significantly reduced PVR compared to placebo:
      191 +/- 9 vs 246 +/- 10 dyne.s.cm-5 at an SaO2 85-90% (P < 0.005) and 233 +/- 12
      vs 293 +/- 18 dyne.s.cm-5 at an SaO2 75-80% (P < 0.05), respectively. Pre
      treatment with losartan, however, had no significant effect on systemic vascular
      resistance although losartan compared to placebo resulted in a significant (P <
      0.05) reduction in mean arterial pressure at an SaO2 75-80%: 78 +/- 2 vs 87 +/- 2
      mmHg. CONCLUSIONS: Losartan had no effect on baseline pulmonary haemodynamics but
      significantly attenuated acute hypoxic pulmonary vasoconstriction, suggesting
      that angiotensin II plays a role in modulating this response in man via its
      effects on the type 1 angiotensin II receptor.

PMID- 8746202
TI  - The contribution of neutrophils to reperfusion arrhythmias and a possible role
      for antiadhesive pharmacological substances.
AB  - OBJECTIVES: It is known that neutrophilic leukocytes contribute to cellular
      damage in the course of cardiac ischemia/reperfusion. A role in arrhythmogenesis,
      although controversial, has been ascribed in some studies to the leukocytes, but
      investigations evaluating possible beneficial effects of inhibitors of neutrophil
      adhesion or transmigration are still missing. METHODS: Isolated spontaneously
      beating rabbit hearts, perfused with saline solution at constant pressure
      according to the Langendorff technique, were treated with 15 min infusion of
      autologous neutrophils. 10 min after the start of this infusion the hearts were
      submitted to coronary occlusion (LAD) for 30 min followed by 30 min reperfusion.
      Four experimental groups were investigated: (1) saline-perfused control hearts,
      (2) leukocyte-perfused hearts, (3) leukocyte-perfused hearts treated with RGDS
      peptide, (4) leukocyte-perfused hearts treated with chondroitin sulfate C. In all
      experiments epicardial potential mapping was carried out (256 unipolar leads). At
      the end of each experiment the hearts were prepared for histology and after
      staining leukocyte accumulation in the ischemic zone, in the border zone and in
      the non-ischemic area was evaluated. RESULTS: In leukocyte-perfused hearts
      submitted to ischemia/reperfusion we found a somewhat enhanced arrhythmogenesis,
      enhanced ST-segment deviation, and a 2-3-fold increase in leukocyte accumulation
      in the ischemic and border zone as compared to the non-ischemic tissue as well as
      increased dispersion of epicardial potential duration especially during
      reperfusion. These changes and the leukocyte accumulation could be suppressed by
      treatment with RGDS and to a somewhat lesser extent with chondroitin sulfate C.
      In addition, arrhythmogenesis could be reduced but not completely suppressed by
      that treatment. CONCLUSIONS: From these results we conclude that: (a) leukocytes
      exert an aggravating effect in arrhythmogenesis during ischemia/reperfusion, (b)
      the arrhythmogenic substrate for this effect may consist of an enhanced
      dispersion of potential duration and (c) that inhibition of leukocyte
      accumulation can at least partially reduce arrhythmogenesis and may be of
      therapeutic interest as an additional treatment.

PMID- 8746203
TI  - Arachidonic acid disrupts calcium dynamics in neonatal rat cardiac myocytes.
AB  - OBJECTIVES: The purpose of this study was to investigate the effects of prolonged
      arachidonic acid (AA) exposure on electrically induced fluctuations of cytosolic
      free Ca2+ concentration ([Ca2+]i) in cardiac myocytes and to identify
      intracellular biochemical events that may play a role in the actions of AA on
      [Ca2+]i dynamics. METHODS: Electrically induced [Ca2+]i transients were
      investigated in cultured single neonatal rat ventricular myocytes using
      spectrofluorometric analysis of fura-2-[Ca2+]i binding. KCl-induced
      depolarization, caffeine and ryanodine were used to assess the effects of AA on
      Ca2+ handling by the sarcolemma and the sarcoplasmic reticulum. Prostanoid
      formation was measured with an ELISA technique. alpha-Tocopherol was used to
      determine if free radical formation was a factor in the AA effects on [Ca2+]i.
      RESULTS: Exposure to 10-30 microM AA produced a concentration-dependent and
      reversible configuration change and eventually a cessation of [Ca2+]i transients.
      Continued exposure resulted in a Ca2+ overload (tonic [Ca2+]i greater than peak
      systolic [Ca2+]i). AA did not influence KCl-induced [Ca2+]i increase but did
      eliminate caffeine-induced [Ca2+]i transients. AA exposure stimulated the
      formation of 6-oxo-prostaglandin F1 alpha in a concentration-dependent manner,
      but thromboxane B2 formation was not influenced. alpha-Tocopherol pretreatment
      significantly delayed times till cessation of [Ca2+]i transients and Ca2+
      overload, whereas ryanodine and cyclo-oxygenase inhibitors were without effect.
      CONCLUSIONS: The present data provide evidence that the initial action of AA on
      [Ca2+]i transients during excitation-contraction coupling involves an effect of
      AA on sarcolemmal Ca2+ influx and sarcoplasmic reticulum Ca2+ handling. AA
      induced cessation of electrically induced [Ca2+]i transients and Ca2+ overload
      may involve the formation of free radicals.

PMID- 8746204
TI  - Disruption of cell-cell adhesion in an inbred strain of hereditary
      cardiomyopathic hamster (Bio 14.6).
AB  - OBJECTIVE: Disarrangement of cardiomyocytes is a pathological characteristic of
      dilated cardiomyopathy. Hereditary cardiomyopathic hamster Bio 14.6, a model of
      dilated cardiomyopathy, displays disorder of cardiomyocyte arrangement. The aim
      of this study was to analyse the disturbance of cell alignment from the point of
      view of the cell-cell adhesion system in Bio 14.6. METHOD: Cardiomyopathic
      hamster Bio 14.6 was used as a model of dilated cardiomyopathy. Histological
      study was performed by light and electron microscopy. Disorder of the adherens
      junction-specific cell-adhesion molecule (A-CAM) was analysed by
      immunofluorescent microscopy and immunoblotting with anti-A-CAM antibody.
      RESULTS: Hematoxylin-eosin staining revealed that intercalated disks were
      identifiable less clearly in cardiomyopathy than in a normal cardiac muscle. It
      was disclosed by electron microscopy that cardiomyocytes adhered to each other
      with reduction in subsarcolemmal electron density at intercalated disks in Bio
      14.6 compared with normal hamsters. We examined the localization of the A-CAM
      molecule in heart by immunofluorescent microscopy. In contrast to normal cardiac
      samples, fluorescence was weak in intensity and unclearly demarcated in the Bio
      14.6 hamsters. We measured the content of A-CAM in the heart. In Bio 14.6
      hamsters, the content of A-CAM was 60 +/- 11% of that measured in normal adult
      hamsters. A-CAM was reduced to a lesser extent (81 +/- 12%) in the newborn
      hamsters. CONCLUSIONS: In Bio 14.6 hamster, structural disturbance of the
      intercalated disks was found on histological examination of the heart.
      Biochemically, A-CAM, which plays a role in intercellular adhesion in
      intercalated disk areas, decreased significantly. These results suggest that
      cardiomyopathy may be accompanied by structural disruption of cell-cell adhesion
      in intercalated disk regions, which may lead to the pathological feature of
      disarranged cardiomyocytes.

PMID- 8746205
TI  - Regulation of InsP3-induced contractions by myoplasmic calcium in permeabilized
      atrial muscle.
AB  - OBJECTIVE: We studied the effect of calcium on inositol 1,4,5-trisphosphate
      (InsP3)-induced contractions in saponin-permeabilized chick atrial muscle (80-100
      microns in diameter). Calcium has been proposed to modulate InsP3-induced
      response and InsP3 binding in other tissue. METHODS: A transient increase in
      tension was used to detect the release of calcium in this multicellular
      preparation. Pulsed (2-3 s) superfusion of either calcium or InsP3 produced a
      transient contraction. RESULTS: Pulsed coapplication of both InsP3 and calcium
      resulted in a contraction greater than that predicted by an additive effect of
      both intracellular messengers. The release of calcium by InsP3 is positively and
      negatively modulated by myoplasmic calcium (EC50 congruent to 0.17 microM and
      IC50 of approximately 1.5 microM). The peak potentiation occurred at
      approximately pCa = 6.3 (0.51 microM free calcium). CONCLUSIONS: These
      observations indicate that an increase of InsP3 in the heart, as produced by
      cardiac neurotransmitters and hormones, may regulate the force of contraction by
      virtue of its synergistic action with calcium. While calcium remains the primary
      trigger for calcium release during excitation-contraction (E-C) coupling, we
      propose that changes in cytoplasmic calcium can modulate InsP3-induced calcium
      release on a beat-to-beat basis. Thus, InsP3 may regulate force generation during
      E-C coupling by activating calcium release during a heart beat.

PMID- 8746206
TI  - Lusitropic effects of a Ca2+ sensitization with a new cardiotonic agent, MCI-154,
      on diseased human hearts.
AB  - OBJECTIVES: Recognition of the problems of conventional cardiotonic agents has
      led to an interest in drugs that produce a positive inotropic action by altering
      the responsiveness of myofilament to Ca2+ (i.e., Ca2+ sensitizing agents). The
      importance of the effects of these compounds on left ventricular (LV) systolic
      function has been emphasized, whereas the effect of them on LV diastolic function
      is still problematic. To investigate the lusitropic action of a novel Ca2+
      sensitizing agent, MCI-154, we compared the effects of MCI-154 on LV relaxation
      and filling dynamics with those of dobutamine in diseased human hearts. METHODS:
      We assessed the slope of the end-systolic pressure-volume relation (Emax), the
      time constant of LV pressure decay (Tw) and the maximum rate of LV early filling
      (dV/dtmax) before and after the infusion of dobutamine (n = 10) or MCI-154 (n =
      9). LV volume and pressure were measured by a conductance catheter and a micro
      tip catheter pressure transducer. RESULTS: When both agents increased Emax
      comparably, dobutamine decreased Tw from 51 to 37 ms and MCI-154 decreased Tw
      from 54 to 44 ms. The decrease of Tw with MCI-154 was less than that with
      dobutamine (17 vs. 29%, P < 0.05). At the same time, dobutamine increased
      dV/dtmax per end-diastolic volume (dV/dtmax/V) from 2.84 to 3.88 s-1, whereas MCI
      154 did not. CONCLUSIONS: Diastolic properties were not compromised by MCI-154,
      though the alteration in them with MCI-154 was less than that with dobutamine
      when MCI-154 increased LV contractile state to the same extent as dobutamine. The
      present results suggest that MCI-154 would be an ideal Ca2+ sensitizing agent
      that enhances force during systole without impairing diastolic function.

PMID- 8746207
TI  - Dietary magnesium deficiency increases Gi alpha levels in the rat heart after
      myocardial infarction.
AB  - OBJECTIVE: Magnesium (Mg) is crucial for the function of G proteins which play
      important roles in mediating the inotropic effects of beta adrenergic agonists in
      the heart and are altered in heart failure. This study was performed to determine
      whether or not dietary Mg deficiency alters functional activity and levels of the
      two major ventricular G proteins, Gi alpha and Gs alpha in the heart after
      myocardial infarction (MI). METHODS: Six week old rats were fed an Mg adequate or
      deficient diet for 6 weeks. At the end of week 3, MI was induced by coronary
      artery ligation. A sham operation was performed as control. After surgery,
      surviving animals were maintained on their assigned diets for another 3 weeks.
      Then, cardiac function was measured, plasma and tissue were collected. RESULTS:
      Severe hypomagnesemia and increased plasma catecholamine level were observed in
      all animals fed the Mg deficient diet. A significant reduction of myocardial Mg
      concentration accompanied by elevated plasma and myocardial calcium
      concentrations was observed in MI animals with existing Mg deficiency vs. animals
      fed the Mg adequate diet. Cardiac function was impaired in MI rats and further
      reduced in MI rats with existing Mg deficiency. Gi alpha level was not altered by
      either Mg deficiency or MI alone, but was dramatically elevated in animals with
      combined Mg deficiency and MI (9.9 +/- 0.7 arbitrary unit.mg-1 protein) as
      compared to MI alone (5.8 +/- 0.6, P < 0.05) and Mg deficiency alone (6.1 +/-
      0.8, P < 0.05). Gs alpha level did not differ between groups. GppNHp-, but not
      fluoride-stimulated adenylyl cyclase activity was slightly reduced in MI animals
      with existing Mg deficiency. CONCLUSION: The findings suggest that dietary Mg
      deficiency increases the expression of Gi alpha in the heart after MI, while
      levels and function of Gs alpha are not compromised during dietary Mg deficiency
      either with or without MI.

PMID- 8746208
TI  - A new method of analysing indicator dilution curves.
AB  - OBJECTIVE: We are currently developing a new indicator dilution method of
      measuring cardiac output using lithium chloride as the indicator. The aim of the
      present study was to develop a simple and accurate method of deriving the area
      under the primary indicator dilution curve: that is, the area which would have
      been inscribed had there been no recirculation of the indicator. METHOD: A model
      based upon the representation of the mixing in the circulation as similar to that
      of the passage of an impulse through a series of filter elements was studied.
      This was represented physically by a model which consisted of a series of mixing
      chambers. The model was analysed theoretically using Laplace transforms and was
      used to test the new method of deriving the area of primary indicator dilution
      curves. RESULTS: Theoretical analysis showed that such a filter model produces
      curves which closely approximate the shape of a lognormal distribution over a
      range of skewness greater than that of human indicator dilution curves. The
      single pass curves from the physical model were shown to be similar in shape to
      lognormal distributions, as were the curves obtained from patients to the point
      when recirculation occurred. A method of estimating the area under the primary
      curve based upon the lognormal distribution was developed and equations derived.
      The use of these equations to calculate flows from lithium dilution curves in the
      mixing chamber model was validated by comparing the results with simultaneous
      timed collection. CONCLUSIONS: Theoretical justification for treating primary
      indicator dilution curves as lognormal is presented. A simple method of deriving
      the integral of the primary indicator dilution curve is described. It uses the
      whole of the curve up to a point short of recirculation, avoiding the problem
      which can occur with the classical Hamilton extrapolation method when the cardiac
      output is low and recirculation distorts the primary curve in the early part of
      the washout.

PMID- 8746209
TI  - Disturbance of peripheral microvascular function in congestive heart failure
      secondary to idiopathic dilated cardiomyopathy.
AB  - OBJECTIVES: Previous studies of peripheral microvascular function in human heart
      failure have concentrated on changes in flow, and there is little information
      concerning the impact of heart failure on the principal determinants of
      transcapillary fluid exchange. This study investigated whether alterations in
      capillary pressure and microvascular fluid permeability can be detected in
      subjects with idiopathic dilated cardiomyopathy. METHODS: Finger nailfold
      capillary pressure and calf capillary filtration coefficient (CFC) were measured
      in parallel studies of two overlapping groups of 12 non-oedematous subjects with
      idiopathic dilated cardiomyopathy and mild to moderate heart failure and in age-
      and sex-matched healthy controls. Capillary pressure was measured by direct
      cannulation using an electronic resistance feedback servonulling technique, and
      CFC by mercury-in-silastic strain gauge plethysmography using a modification of
      the technique which avoids assumptions concerning isovolumetric venous pressure.
      RESULTS: Following correction for differences in skin temperature, capillary
      pressure was lower in the subjects with heart failure (P = 0.02). Both CFC and
      isovolumetric venous pressure were greater in the subjects with heart failure
      than in controls (3.4 +/- 0.9 vs. 2.6 +/- 0.7 ml.min-1.mmHg-1.100 ml-1, P = 0.03;
      27.1 +/- 8.4 vs. 17.2 +/- 7.2 mmHg, P = 0.01). CONCLUSIONS: These data suggest
      that factors other than changes in arterial inflow and venous outflow pressures
      are likely to play an important role in the disruption of microvascular
      homeostasis which occurs in heart failure. Changes in capillary hydraulic
      conductance may contribute to the pathogenesis of oedema.

PMID- 8746210
TI  - Preischaemic as well as postischaemic application of a Na+/H+ exchange inhibitor
      reduces infarct size in pigs.
AB  - BACKGROUND: During reperfusion of ischaemic myocardium, Na+/H+ exchange promotes
      recovery from acidosis resulting in an accumulation of intracellular Na+. This
      leads to calcium overload via Na+/Ca2+ exchange and might result in cell necrosis
      contributing to reperfusion injury. METHODS AND RESULTS: We assessed whether HOE
      694, a specific inhibitor of Na+/H+ exchange, is able to reduce infarct size in
      swine myocardium. Experiments were performed in pentobarbitone-anaesthetized,
      open-chest pigs which were subjected to a 60 min occlusion of the left anterior
      descending coronary artery (LADCA) followed by 2 h of reperfusion. Three groups
      of animals were studied. In the pre-reperfusion group (pre-REP, n = 7) HOE 694
      infusion (7 mg/kg/15 min) was started at 45 min of occlusion of the LADCA and
      continued until the end of occlusion, while in pre-occlusion group (pre-TCO, n =
      7) HOE 694 infusion was started 15 min before occlusion and stopped at the onset
      of ischaemia. In the control group (n = 7) animals received vehicle alone. At the
      end of the protocol, infarct size (as d% of the left ventricular risk region) was
      determined by the p-nitroblue tetrazolium method. Treatment with HOE 694 prior to
      the ischaemic insult or upon reperfusion significantly reduced infarct size
      [4.1%(1.4%), P < 0.01 and 38.2%(5.8%), P < 0.05, respectively], compared with
      77.7%(4.0%) in the control group. However, infarct size was significantly more
      reduced in the pre-TCO group than in the pre-REP group (P < 0.05). CONCLUSION:
      Treatment with HOE 694 leads to a significant reduction in infarct size, even
      when administered after the onset of ischaemia. Thus, inhibition of Na+/H+
      exchange was able to limit cell necrosis. This implicates an important role for
      Na+/H+ exchange in the pathogenesis of infarct expansion and provides evidence
      that reperfusion injury exists. However, HOE 694 was even more effective when
      given before ischaemia, indicating an additional protective effect during
      ischaemia which might be due to slowing down of a vicious cycle that consumes ATP
      and generates H+.

PMID- 8746211
TI  - Temporal relationships between levels of circulating NO derivatives, vascular NO
      production and hyporeactivity to noradrenaline induced by endotoxin in rats.
AB  - OBJECTIVE: Lipopolysaccharide (LPS) induces early (within 1 h) and delayed (after
      several hours) impairment of vascular reactivity to catecholamines whose
      mechanisms are different, although they probably both involve nitric oxide (NO).
      Temporal and quantitative relationships between hyporeactivity to noradrenaline
      and NO production were investigated in a rat model of endotoxaemia allowing to
      clearly distinguish the two phases of hyporeactivity. METHODS: Anaesthetised rats
      were infused with LPS (14 mg kg-1 h-1) for 1 h. Pressure responses to
      noradrenaline (NA) and circulating NO derivatives (nitrosyl haemoglobin, NO2-,
      NO3-) were monitored for 5 h after the onset of infusion. Reactivity to NA and
      tissue cyclic GMP level were also assessed ex vivo, in aortic rings taken at
      different experimental times. RESULTS: LPS-induced early hyporeactivity to NA was
      associated with a moderate but significant increase in plasma NO3- level, without
      any significant change in concentration of the other circulating NO derivatives.
      Neither reactivity ex vivo nor cyclic GMP content were modified in aortae taken
      after 1 h of LPS infusion. By contrast, delayed hyporeactivity (5 h after the
      onset of LPS infusion) was associated with a large increase in all circulating NO
      derivatives (up to 2.5 fold), enhanced aortic cyclic GMP level and aortic
      hyporeactivity ex vivo. Pre-treatment of rats with NG-nitro-L-arginine methyl
      ester (1 mg kg-1 i.v.) entirely prevented early hyporeactivity and rise in NO3-
      concentration. In addition it attenuated in comparable proportion both delayed
      hyporeactivity to NA in vivo and circulating levels of NO derivatives.
      CONCLUSION: The results confirm the involvement of NO in the two phases of
      hyporeactivity to NA induced by LPS. They strongly support the view that a
      circulating factor is involved in triggering endothelial NO release during the
      early phase, whereas the delayed phase is associated with a high production of NO
      in vascular smooth muscle resulting from the induction of NO synthase.

PMID- 8746212
TI  - Indirect evidence for stimulation of nitric oxide release by tumour necrosis
      factor-alpha in human veins in vivo.
AB  - OBJECTIVES: The detrimental haemodynamic changes observed in septicaemia are
      generalised vasodilation, arterial hypotension, and hyporesponsiveness to
      vasopressor compound, all of which could be explained by the release of an
      endogenous vasodilator. Experimental and clinical evidence suggests that tumour
      necrosis factor-alpha (TNF) induces the expression of vascular nitric oxide (NO)
      synthase within hours and that NO released from smooth muscle cells could be
      involved in the pathogenesis of septic shock. The aim of this study was to
      investigate the role of NO in the vascular effects of TNF. METHODS: Using the
      dorsal hand vein compliance technique, the effect of the NO synthase inhibitor L
      NG-monomethyl-arginine (L-NMMA) on alpha 1-adrenergic responsiveness
      (phenylephrine 1.25-8000 ng/min) was studied after prolonged local venous
      infusion of TNF (8.7 micrograms in 5 h) in 9 volunteers and in 6 volunteers
      without previous cytokine exposure. RESULTS: Mean (+/- s.e.) maximum
      phenylephrine constriction (Emax) was 73 +/- 6% and log dose-rates exerting 50%
      of Emax (log ED50) were 3.2 +/- 0.09 (geometric mean: 1535 ng/min). Local co
      administration of L-NMMA at a dose sufficiently high to block NO formation (3.4
      mumol/min) increased venous sensitivity to phenylephrine threefold (log ED50 2.8
      +/- 0.1, P < 0.015; geometric mean: 574 ng/min) whereas Emax was similar (73 +/-
      5%). In the controls the phenylephrine dose-response relationship remained
      unaffected by simultaneous administration of L-NMMA. CONCLUSIONS: As no basal
      release of NO occurs in hand veins without previous exposure to TNF these results
      provide direct evidence for induction of NO formation in the human vasculature
      and consecutive resistance to alpha-adrenergic venoconstriction. NO might,
      therefore, be a key mediator of haemodynamic impairment in humans under
      conditions with known elevations of circulating TNF, such as a septic shock.

PMID- 8746213
TI  - Cardioprotection by liposome-conjugated sialyl Lewisx-oligosaccharide in
      myocardial ischaemia and reperfusion injury.
AB  - OBJECTIVES: Selectins are important adhesion molecules which utilize a
      carbohydrate ligand such as sialyl Lewisx (SLex). Our objective was to study the
      effects of a liposome-conjugated SLex (Lipo-SLex) in myocardial ischaemia (MI)
      and reperfusion (R) injury in order to further clarify the actions of this
      carbohydrate. METHODS: We studied the efficacy of Lipo-SLex in a feline model of
      MI (90 min) and R (270 min) injury in vivo. Lipo-SLex (400 micrograms SLex/kg,
      iv) was administered intravenously 10 min prior to R. We also utilized an in
      vitro system of neutrophil adherence to thrombin-stimulated coronary endothelium
      to validate the efficacy of Lipo-SLex. RESULTS: Lipo-SLex significantly
      attenuated myocardial necrosis (8.6 +/- 1.2 vs. 29.5 +/- 3.1% of area-at-risk, P
      < 0.01) and plasma creatine kinase activities (P < 0.01) compared to vehicle
      (liposome alone). Moreover, endothelium-dependent relaxation to acetylcholine and
      A23187 in ischaemic-reperfused coronary rings obtained from cats treated with
      Lipo-SLex was significantly preserved compared to cats given liposomes without
      SLex (P < 0.01). After reperfusion, ex vivo PMN adherence to ischaemic-reperfused
      coronary endothelium was significantly increased in vehicle-treated cats,
      however, this was significantly attenuated in Lipo-SLex-treated cats (82 +/- 7
      vs. 28 +/- 3 PMNs/mm2, P < 0.01). Myeloperoxidase activity in the ischaemic
      myocardium, a marker of PMN accumulation, was also significantly attenuated in
      Lipo-SLex-treated cats compared to liposomes without SLex (P < 0.01).
      CONCLUSIONS: Liposome-conjugated SLex-oligosaccharide attenuates myocardial
      necrosis and preserves coronary endothelial function following MI/R in vivo. The
      mechanism appears to be mediated by inhibition of the initial PMN-endothelial
      interaction and eventual accumulation into the ischaemic cardiac tissue. The
      liposome-SLex complex may be an efficient drug formulation for acute inflammatory
      diseases.

PMID- 8746214
TI  - Cell-specificity and signaling pathway of endothelin-1 gene regulation by
      hypoxia.
AB  - OBJECTIVES: Endothelin-1 (ET-1) is a potent vasoconstrictor that is expressed in
      endothelial cells and in many other cells and tissues. Increased plasma levels of
      the peptide have been associated with ischemic heart disease, atherosclerosis,
      and myocardial infarction. The objectives of the current study were (1) to
      determine the tissue specificity for induction of the ET-1 gene by hypoxia, (2)
      to determine whether the hypoxia regulatory pathway is the same as that in other
      hypoxia regulated genes and (3) to analyze the contributions of protein kinases
      for basal and induced expression of ET-1. METHODS: ET-1 transcript levels were
      measured by Northern blot and quantitative polymerase chain reaction in
      endothelial and non-endothelial cells following exposure to hypoxia. Regulatory
      steps within the pathway were identified by treating aerobic or hypoxic cultures
      with cycloheximide, PMA, a series of selective protein kinase inhibitors, and
      transition metals. The effects on ET-1 transcripts were compared with the
      ubiquitous hypoxia inducible pyruvate kinase gene. RESULTS: The induction of ET-1
      by hypoxia in vitro occurred exclusively in early passage endothelial cells. This
      induction was prevented by treatment with the protein synthesis inhibitor
      cycloheximide and was at least partially mimicked by treatment with transition
      metals. Induction by hypoxia was not effected by inhibitors of protein kinase C,
      protein kinase A, calcium-calmodulin dependent protein kinase, or cyclic GMP
      dependent protein kinase. The basal expression was decreased and hypoxic
      induction was eliminated by treating cells with tyrosine kinase-selective
      inhibitors. CONCLUSIONS: Et-1 induction by hypoxia requires endothelial cell
      specific factor(s) or steps, new protein synthesis, and may involve a haeme
      protein-containing pathway in oxygen sensing. A protein tyrosine kinase step is
      implicated for both basal and induced expression of the ET-1 gene.

PMID- 8746215
TI  - Stress triggers different pathophysiological mechanisms in younger and older
      cardiomyopathic hamsters.
AB  - OBJECTIVES: Because cardiomyopathic hamsters (CMHs) in the lesion-forming period
      of their disease are more susceptible to the lethal effects of stress than older
      CMHs, we tested the hypothesis that different pathophysiological effects of
      stress may occur: coronary vasospasm in younger CMHs and congestive heart failure
      in older ones. METHODS: CMHs aged 2.5 and 6.5 months were stressed with 2 h
      supine cold immobilization for 5 consecutive days. Three, 5 and 7 days after
      stress, the hearts were excised and perfused using a modified Langendorff system.
      Maximum +/- dP/dt, developed pressure, ventricular relaxation time (Tau) and
      coronary vascular resistance (CVR) were recorded and CVR was also measured
      following coronary infusion of arginine vasopressin (AVP). RESULTS: Stress
      produced ventricular dysfunction (decreased maximum +/- dP/dt, developed
      pressure, and increased Tau) in older CMHs (P < 0.05) but not in younger CMHs.
      Baseline CVR in younger CMHs was significantly higher than in older CMHs (P <
      0.01) and AVP infusion produced a bigger increase in CVR in younger stressed CMHs
      than in either younger nonstressed or older stressed CMHs (P < 0.05). CONCLUSION:
      The younger CMH heart exhibits greater resting vascular tone and stress produces
      coronary vasoconstriction that is consistent with coronary spasm. In contrast,
      the older CMH experiences a decrease in cardiac function which remains 7 days
      after stress and indicates an exacerbation of CHF from the mild form existing
      prior to stress. The lethal effects of stress may occur because of the activation
      of different pathological processes in younger and older CMHs.

PMID- 8746216
TI  - Common arterial trunk and pulmonary atresia: close developmental cousins? results
      from a teratogen induced animal model.
AB  - OBJECTIVES: To examine morphological similarities between "classically different"
      congenital heart lesion types induced in fetal rats by the cardiac teratogen N,N'
      bis(dichloroacetyl)-1,8-octamethylenediamine (bis-diamine). METHODS: A single 200
      mg oral dose of bis-diamine was given to 50 pregnant rats on the 9th gestational
      day. Eleven controls were fed an inert vehicle. Experimental and control rats
      were sacrificed from 15.4 days to term and embryos delivered by caesarean
      section. Age-matched embryos were processed for histology and sectioned at 7
      microns. Cardiac morphology was compared between normal and bis-diamine exposed
      groups. RESULTS: Hearts from control embryos were morphologically normal. Those
      from bis-diamine treated embryos exhibited common arterial trunk (32%),
      overriding aortic valve with valvar pulmonary stenosis (40%) or infundibular
      atresia (4%), or ventricular septal defect (24%). Development of the outlet
      septum was affected in all hearts and the arterial duct was absent in 72% of
      cases. Whilst most hearts demonstrated the anatomy expected for their lesion,
      some with a common arterial valve demonstrated a pulmonary blood supply similar
      to that in human cases of pulmonary atresia, where, in the absence of an arterial
      duct, an essential systemic to pulmonary conduit was provided by a "persistent
      fifth aortic arch artery". In one such case the proximal part of the
      aortopulmonary septum was identified above a common valve. The septum was
      deviated to the left and was not continuous throughout the length of the arterial
      trunk, causing atresia of the pulmonary component. Others had muscular
      infundibular atresia but with a pulmonary blood supply arising directly from the
      solitary trunk as seen in common arterial trunk "type III". CONCLUSIONS: Bis
      diamine consistently affects development of those structures which partition the
      arterial segment of the developing heart at one or more levels, often coexistent
      with agenesis of the sixth aortic arch arteries. Whilst the aortopulmonary and
      outlet septums were absent in most cases of common arterial trunk, some
      morphological duality was shared by classically different lesion types in these
      rat hearts, which may suggest a common aetiology for common arterial trunk "type
      III" and aortic overriding with absence of the outlet septum and pulmonary
      atresia.

PMID- 8746217
TI  - A protective role of nitric oxide in isolated ischaemic/reperfused rat heart.
AB  - OBJECTIVES: The importance of NO-induced vasodilator tone in maintaining adequate
      coronary flow to sustain hemodynamic function in aerobically perfused heart and
      the role of NO in the injury development in ischaemic/reperfused heart was
      studied. METHODS: Effect of NO synthesis inhibitor (N omega-nitro-L-arginine, L
      NOARG) on isolated working rat hearts subjected to either 90 min of aerobic
      perfusion or to a global ischaemia (27.5 to 42.5 min) followed by 40 min
      reperfusion was studied. To overcome coronary flow reducing effect of L-NOARG
      either perfusion pressure was raised from 75 to 120 cm H2O or adenosine (400 nM)
      was administered. RESULTS: In the hearts perfused at coronary pressure of 75 and
      120 cm H2O, L-NOARG (10 microM) reduced coronary flow by 30% and 17%,
      respectively, while cardiac output was not affected. Only a transient increase in
      adenosine and lactate outflow occurred in L-NOARG-treated hearts. The post
      ischaemic recovery of functions was impaired in L-NOARG-treated hearts, an effect
      not correlating with L-NOARG-induced reduction in coronary flow. Although the pre
      ischaemic coronary flow was similar in the untreated hearts perfused at 75 cm H2O
      and in L-NOARG-treated hearts perfused at 120 cm H2O, the post-ischaemic recovery
      in the latter group was still impaired as compared to that in the untreated
      hearts. Likewise, coronary flow was similar in the untreated hearts and in those
      treated with L-NOARG plus adenosine, nevertheless, the post-ischaemic recovery in
      the latter group was impaired as compared to that in the untreated hearts.
      CONCLUSIONS: While the inhibition of NO synthesis resulted in coronary flow
      reduction it did not induce a state of permanent ischaemia in isolated rat heart.
      L-NOARG-induced augmentation of the ischaemia/reperfusion injury was related to
      the deficit of NO, itself, rather than to the reduction in myocardial perfusion.

PMID- 8746218
TI  - Hypoxia induces PMN adherence to umbilical vein endothelium.
AB  - OBJECTIVE: In vitro incubation of cultured endothelial cells under hypoxia leads
      to the activation of these cells and results in an increase of their adhesiveness
      for neutrophils (PMN). Because of the possible relevance of these observations
      for pathological situations, we investigated whether adherence of PMN also occurs
      in an entire vein after its incubation in hypoxic conditions. METHODS: Human
      umbilical veins in complete cords were incubated for 2 h in normoxic or hypoxic
      conditions and the adherence of unstimulated human 51Cr-labelled-PMN was measured
      under flow conditions. Experiments with human umbilical vein endothelial cells
      (HUVEC) were performed in parallel for comparison. Morphological studies in
      scanning electron microscopy were carried out in both in vitro and ex vivo
      situations. RESULTS: Hypoxia induced an increase in the adherence of PMN either
      to HUVEC or to the umbilical vein endothelium up to 5- to 6-fold when compared to
      normoxic conditions (P < 0.001). In both cases, this hypoxia-induced adherence
      was inhibited by anti-ICAM-1 antibodies or when the PAF (platelet-activating
      factor) synthesis was blocked during hypoxia by oleic acid. Furthermore, the
      adherence of PMN was inhibited when PMN were pre-incubated with WEB 2086 (a
      selective PAF receptor antagonist). These results indicate a crucial role of PAF
      in this process. Morphological studies confirmed that the number of PMN adherent
      to hypoxic HUVEC or to the hypoxic umbilical vein endothelium was much greater
      than the number of PMN on normoxic endothelial cells. Both in vitro and ex vivo,
      PMN adherent to the hypoxic endothelial cells to the contrary of the ones
      adherent to normoxic endothelial cells demonstrated membrane foldings typical of
      an activated state. CONCLUSION: These results show that in a complete vein,
      hypoxia induced an increased adhesiveness of endothelial cells for PMN by a
      similar mechanism to the one observed for cultured endothelial cells. They
      suggest an active role of endothelial cells in the initiation of the inflammatory
      response often described in ischemic-reperfused organs.

PMID- 8746219
TI  - Endocardial and epicardial infarct size after preconditioning by a partial
      coronary artery occlusion without intervening reperfusion. Importance of the
      degree and duration of flow reduction.
AB  - OBJECTIVE: Recently, we reported that a partial coronary artery occlusion
      immediately preceding a sustained coronary artery occlusion limited infarct size.
      We now investigated whether the protection by partial coronary artery occlusions
      (i) depends on the severity and(or) duration of the flow reduction and (ii)
      varies in the different myocardial layers. METHODS: In 71 open-chest pigs (eight
      groups) left ventricular area at risk (AR) and infarct area (IA) were determined
      for the endocardial (IAendo and ARendo) and epicardial halves (IAepi and ARepi).
      RESULTS: In control animals (60 min total coronary artery occlusion (TCO)
      followed by 120 min reperfusion (Rep)) there were highly linear relations between
      IA and AR in the endocardium (r = 0.98, P < 0.01) and epicardium (r = 0.97, P <
      0.01), which could be described by IAendo = 1.01 ARendo - 4.5 and by IAepi =
      0.88ARepi - 3.6, respectively. In animals that underwent a 10 min TCO + 15 min
      Rep prior to the 60 min TCO + 120 min Rep, IA in both myocardial layers were
      again highly linearly related with AR, with less steep slopes for both the
      endocardium (0.63) and epicardium (0.57) (both P < 0.01). Two groups of pigs were
      subjected to either a 30 or 90 min 70% reduction in coronary blood flow (FR)
      immediately preceding the 60 min TCO + 120 min Rep, without intervening
      reperfusion. A 30 min 70% FR decreased IA to the same degree in the endo- and
      epicardial half. A 90 min 70% FR resulted in protection in the epicardium (P <
      0.01) but not in the endocardium, most likely because 90 min 70% FR without 60
      min TCO already caused infarction which was more severe in the endo- than in the
      epicardium (P < 0.01). Endocardial and epicardial IA after either a 30 or 90 min
      30% FR prior to the 60 min TCO was not different from that in the control group,
      indicating that this mild flow reduction failed to limit irreversible damage.
      CONCLUSIONS: Thirty or ninety min of severe (70%) but not mild (30%) coronary
      flow reductions protected against myocardial infarction. The protection by a 70%
      FR was influenced by the duration of FR as a 30 min 70% FR similarly decreased IA
      in the endocardial and epicardial halves, while 90 min 70% FR preferentially
      limited IA in the epicardial half. These findings suggest that perfusion
      abnormalities immediately preceding an infarction could be an important source of
      infarct size variability in patients.

PMID- 8746220
TI  - Platelet-activating factor (PAF) does not affect diastolic function in isolated
      rat hearts.
AB  - Platelet-activating factor might be responsible for the alterations of diastolic
      function observed in different disease states and these potential effects have
      not been studied. The effect of incremental concentrations of platelet-activating
      factor (to a maximum of 200 nM) was therefore examined in isolated perfused rat
      heart. Platelet-activating factor decreased coronary flow rate and contractility
      in a dose-dependent manner. Although high-dose platelet-activating factor
      decreased peak -dP/dt compared to baseline, this was not significant when
      compared to vehicle-administered control. There were no changes in the time
      constant of left ventricular relaxation and the chamber stiffness constant. These
      results do not support a major direct role of platelet-activating factor in
      diastolic dysfunction.

PMID- 8746221
TI  - Hydrogen peroxide as a protective agent during reperfusion. A study in the
      isolated perfused rabbit heart subjected to regional ischemia.
AB  - In spite of extensive research during the last decade it has not been possible to
      prove that endogenously generated hydrogen peroxide or any reduced oxygen species
      reaches sufficient concentration during reperfusion after myocardial ischemia to
      contribute significantly to irreversible cell injury. In an attempt to further
      test this hypothesis we subjected isolated perfused rabbit hearts to 30 min
      regional ischemia followed by reperfusion and supplied hydrogen peroxide in low
      levels with or without catalase during the first 30 min of reperfusion and
      thereafter continued the reperfusion for a total of 120 min. Five different
      groups were studied: controls, and hearts supplied with 2 microM H2O2, 1 microM
      H2O2, 1 microM H2O2 + catalase (IU/l) or catalase alone in the initial part of
      the reperfusion. At the end of 120 min reperfusion, area at risk was measured
      with fluorescent particles and infarct zone size with tetrazolium staining. The
      results were: in the control group 32 +/- 5.0% of the risk zone infarcted, in the
      2 microM H2O2 group 16.3 +/- 5.6% and in the 1 microM H2O2 group 6.9 +/- 0.8% (P
      < 0.05 compared to control). The reduction in infarct size was not present when
      catalase was added to the hydrogen peroxide-containing solution (26.4 +/- 4.5) or
      if catalase was present alone (22.9 +/- 1.8% infarction). In conclusion, hydrogen
      peroxide, 1 microM, protected the heart during reperfusion and reduced the amount
      of cell death after 120 min of reperfusion. The study demonstrated reduction or
      delay in infarction based only on treatment in the reperfusion period. The
      mechanism behind this protection remains to be determined.

PMID- 8746222
TI  - Vascular calcium overload produced by vitamin D3, in rats. Effect of treatment
      with SR 33805, a novel calcium entry blocker.
AB  - The effect of SR 33805, a novel calcium entry blocker, on calcium overload was
      studied in six vascular beds in rat. Fantofarone, a parent compound, and
      verapamil were used as reference calcium entry blockers. Calcium overload induced
      with a single dose (300,000 IU, i.m. of vitamin D3) was measured by means of
      atomic absorption and histological techniques. From the time-course of calcium
      overload, a treatment period of 3 days was selected to determine the effects of
      drug treatment. The compounds were given orally twice a day in the following dose
      ranges: SR 33805 2-100 mg/kg, fantofarone 10-300 mg/kg, verapamil 100 mg/kg. SR
      33805 significantly decreased the calcium content beginning at the dose of 2
      mg/kg in the thoracic aorta, 5 mg/kg in the mesenteric artery and 30 mg/kg in the
      heart. Fantofarone and verapamil had the same effect at the dose of 100 mg/kg.
      Histological assessment of the heart revealed that lesions appearing in the
      tissue adjacent to the arteries were significantly diminished by treatment with
      SR 33805 at a dose which produced a significant decrease in the arterial calcium
      content. Thus, SR 33805 can inhibit both calcium overload and its deleterious
      consequences and its actions are evident at doses as low as 2 mg/kg.

PMID- 8746223
TI  - The effect of in vivo retinal cooling on the electroretinogram of the rabbit.
AB  - PURPOSE: Studies reporting the effect of retinal cooling on the electroretinogram
      of mammals have, in most cases, made use of an in vitro approach where the
      temperature of the retina was lowered by reducing the temperature of the bathing
      media. The purpose of our study was to investigate, in rabbits, the effect of in
      vivo retinal cooling using an experimental approach never before reported in
      order to determine if some of the temperature-related ERG effects previously
      shown could have been, in part, amplified by alterations in the physiological
      status of the retina due to preparation for in vitro study. METHODS: In order to
      reduce the temperature of the retina, a 20 gauge plastic tubing was coiled around
      the eye from the limbus to the optic nerve head and glued to the sclera. Cold (15
      degrees C) tap water entered the tubing at the limbal extremity and exited (18
      degrees C) at the optic nerve extremity. Intraretinal temperature was measured to
      be within 1 degrees C of that of the circulating water. RESULTS: Our results
      indicate that with progressive retinal cooling the a- and b-waves are gradually
      reduced to 66.9 +/- 17.3 and 90.9 +/- 10.4% of control respectively. The most
      dramatic temperature induced ERG modifications were observed in the oscillatory
      potential recordings where the mean summed OP amplitude (OP2 + OP3 + OP4) was
      reduced to less than 23.9 +/- 13.5% of control with OP2 being the least affected.
      The peak times of all the ERG components were significantly delayed with cooling.
      CONCLUSIONS: Of all the ERG components examined, the OPs were those most severely
      affected by our manipulation. We believe that our results constitute further
      evidence in support of the concept that the OPs are more sensitive to retinal
      disturbance than the b-wave.

PMID- 8746224
TI  - Monocular dot-density cues in random-dot stereograms.
AB  - In the original random-dot stereograms (RDSs) invented by Julesz, binocular
      disparity could only take on values that were integral multiples of dot width.
      The other common method for constructing RDSs (the projection method) relaxes
      this restriction. However, the projection method can introduce dot-density cues
      into the monocular images. When polar projection is employed, density variation
      is introduced as an expression of perspective cues; when parallel projection is
      employed, there are no perspective cues, but density variation is nonetheless
      introduced whenever disparity varies as a function of horizontal position. de
      Vries, Kappers, and Koenderink [(1994) Vision Research, 34, 2409-2423] proposed
      to minimize the density cues by selecting half of the random dots from a uniform
      random distribution in the right-eye image, projecting them onto the cyclopean
      surface, and then projecting them back to the left eye image and vice versa. In
      this paper the precise nature of the density cues introduced by the projection
      method, and by de Vries et al.'s modification of that method, are derived. It is
      also shown that the projection method and its modification have very similar
      density cues near the medial sagittal plane when polar projection is employed,
      and that they have identical density cues over the entire random-dot field when
      parallel projection is employed.

PMID- 8746225
TI  - Brightness of uniform stabilized fields.
AB  - Brightness of uniform fields during normal and stabilized viewing was determined
      as a function of adapting luminance, field size, and luminance gradient of the
      edges of the adapting field. In one set of experiments, it was found that, over a
      range of adapting luminances from 6 to 9600 td, a uniformly-illuminated 7.5 deg
      hemifield appeared about 1 log unit brighter in normal viewing than when it was
      retinally-stabilized. In the second set of experiments, it was found that the
      loss of brightness due to stabilized viewing was significantly greater for large
      fields with raised cosine edges than for small fields with step edges. Both sets
      of results can be accounted for by a two-stage model of light adaptation
      previously proposed to account for the fading time of stabilized images.

PMID- 8746226
TI  - Linking object boundaries at scale: a common mechanism for size and shape
      judgments.
AB  - The area over which boundary information contributes to the determination of the
      center of an extended object was inferred from results of a bisection task. The
      object to be bisected was a rectangle with two long sinusoidally modulated sides,
      i.e. a wiggly rectangle. The spatial frequency and amplitude of the edge
      modulation were varied. Two object widths were tested. The modulation of the
      perceived center approximately equaled that of the edges at very low edge
      modulation frequencies and decreased in amplitude with increasing edge modulation
      frequency. The edge modulation had a greater modulating effect on the perceived
      center for the narrower object than for the wider object. This scaling with
      object width didn't follow perfect zoom invariance but was precisely matched by
      the scaling of the bisection threshold with width, strongly supporting the idea
      that the same mechanism determines both the location of the perceived center for
      these stimuli and its variance. We propose that this mechanism is the linking of
      object boundaries at a scale determined by the object width.

PMID- 8746227
TI  - Mechanisms underlying the detection of increments in parafoveal retina.
AB  - It is well established that the spectral sensitivity under photopic conditions
      varies across the human retina. We investigate the mechanisms underlying these
      spectral changes. Through the use of color appearance, flicker sensitivity,
      additivity, discrimination at threshold and modeling, we show that the changes in
      spectral sensitivity on a photopic white background across parafoveal retina are
      consistent with shifts in cone weightings to (L-M) and (M-L) chromatic channels.
      This two channel model, developed to account for foveal spectral sensitivity
      curves (Sperling & Harwerth, 1971 Science, 172, 180-184), provides a better
      description of parafoveal data than both a single color channel upper envelope
      model (comprised of a single red-green opponent channel and an achromatic
      mechanism) and a vector model (combining a red-green opponent channel with an
      achromatic component). Thus while the two channel model ([L-M] and [M-L]) of
      foveal color vision is generalizable to the parafovea, simple models with a
      unitary red/green process are not. Although the two channel model can accurately
      fit parafoveal spectral sensitivity curves without it, a small contribution from
      a luminance mechanism might improve the ability of the two channel model to
      account for threshold discrimination and additivity data.

PMID- 8746228
TI  - Is the site of non-linear filtering in stereopsis before or after binocular
      combination?
AB  - There is recent evidence that both linear and non-linear filtering operations
      subserve stereoscopic localization. For example, for spatially band-pass stimuli,
      the overall Gaussian envelope, which is not explicitly represented by the output
      of linear filters, can provide coarse disparity information. Here we ask three
      questions about the nature of this non-linear processing in stereopsis. First, is
      the site of the non-linearity before or after binocular combination? Second, is
      the stimulus envelope extracted by orientation or non-orientation selective
      spatial filters? Finally, we ask whether the envelope-based 3-D localization
      performance is similar to that for monocular 2-D localization as would be the
      case if the localization of the monocular contrast envelope was common to both
      operations. Our results suggest that envelope extraction occurs before binocular
      combination and that the filters involved are orientation selective. Finally, we
      provide preliminary evidence that is compatible with the proposal that 3-D and 2
      D localization use the same envelope extraction operations.

PMID- 8746229
TI  - The efficiency of different cue types for reducing spatial-frequency uncertainty.
AB  - Detection experiments reveal that performance is decreased when the signal's
      spatial frequency varies unpredictably across trials compared with conditions
      where it is held constant. However, this effect can more or less be compensated
      by presenting cues shortly before each trial. To investigate the efficiency of
      different sensory and symbolic cue types a signal-detection experiment with
      spatial-frequency uncertainty was carried out. The inter-stimulus interval
      between cue and signal as well as for the sensory cue types, the spatial overlap
      between cue and signal, was varied. The results reveal appreciable efficiency
      differences. While some cues were only of little help, others reduced uncertainty
      almost entirely. However, the efficiency of cues which were identical to the
      signals was severely restricted by forward-masking effects when they were
      presented at the same position as the signal.

PMID- 8746230
TI  - A linear systems approach to the detection of both abrupt and smooth spatial
      variations in orientation-defined textures.
AB  - Two distinct paradigms have characterized most previous studies of texture
      perception: one has dealt with texture segregation, the other with the processing
      of texture gradients. Typically, studies of texture segregation have used stimuli
      with abrupt textural variations, whereas studies of texture gradient processing
      have used stimuli with smooth textural variations. In this study we have asked
      whether the mechanisms which process abrupt and smooth textural variations are
      the same, by considering whether a simple linear model can account for the
      detection of orientation modulation in micropattern-based textures with three
      types of modulation: sine-wave (SN), square-wave (SQ) and missing fundamental
      (MF). The MF waveform was constructed by removing the fundamental harmonic from a
      square-wave. We found a clear overall ordering of sensitivity: SQ > SN > MF. We
      found that sensitivity to the SQ and MF stimuli could be predicted very well from
      the SN data if one assumed that the r.m.s. output of a single linear channel
      underlay the detection of the orientation modulation. This suggests that the
      detection of both abrupt and smooth changes in orientation-defined textures is
      subserved by a common mechanism which mimics the operation of a single linear
      channel.

PMID- 8746231
TI  - Recovery from adaptation for dynamic and static motion aftereffects: evidence for
      two mechanisms.
AB  - The motion aftereffect (MAE) is an illusory drift of a physically stationary
      pattern induced by prolonged viewing of a moving pattern. Depending on the nature
      of the test pattern the MAE can be phenomenally different. This difference in
      appearance has led to the suggestion that different underlying mechanisms may be
      responsible and several reports show that this might be the case. Here, we tested
      whether differences in MAE duration obtained with stationary test patterns and
      dynamic test patterns can be explained by a single underlying mechanism. We find
      the results support the existence of (at least) two mechanisms. The two
      mechanisms show different characteristics: the static MAE (i.e. the MAE tested
      with a static test pattern) is almost completely stored when the static test is
      preceded by a dynamic test; in contradistinction, the dynamic MAE is not stored
      when dynamic testing is preceded by a static test pattern.

PMID- 8746232
TI  - A second-order pattern reveals separate strategies for encoding orientation in
      two-dimensional space and space-time.
AB  - We measured the perceived spatial orientation of the low contrast regions of
      contrast modulated sine gratings. Subjects make systematic errors which depend
      upon the carrier spatial frequency and the angle between the carrier grating and
      the modulation. The results for the spatial orientation task are compared with a
      motion domain analogue. The difference in the pattern of results for these two
      tasks suggests there exist separate strategies for encoding orientation in two
      dimensional space and space-time.

PMID- 8746233
TI  - Estimating heading during real and simulated eye movements.
AB  - The ability to judge heading during tracking eye movements has recently been
      examined by several investigators. To assess the use of retinal-image and extra
      retinal information in this task, the previous work has compared heading
      judgments with executed as opposed to simulated eye movements. For eye movement
      velocities greater than 1 deg/sec, observers seem to require the eye-velocity
      information provided by extra-retinal signals that accompany tracking eye
      movements. When those signals are not provided, such as with simulated eye
      movements, observers perceive their self-motion as curvilinear translation rather
      than the linear translation plus eye rotation being presented. The interpretation
      of the previous results is complicated, however, by the fact that the simulated
      eye movement condition may have created a conflict between two possible estimates
      of the heading: one based on extra-retinal solutions and the other based on
      retina-image solutions. In four experiments, we minimized this potential conflict
      by having observers judge heading in the presence of rotations consisting of
      mixtures of executed and simulated eye movements. The results showed that the
      heading is estimated more accurately when rotational flow is created by executed
      eye movements alone. In addition, the magnitude of errors in heading estimates is
      essentially proportional to the amount of rotational flow created by a simulated
      eye rotation (independent of the total magnitude of the rotational flow). The
      fact that error magnitude is proportional to the amount of simulated rotation
      suggests that the visual system attributes rotational flow unaccompanied by an
      eye movement to a displacement of the direction of translation in the direction
      of the simulated eye rotation.

PMID- 8746234
TI  - A geometric basis for measurement of three-dimensional eye position using image
      processing.
AB  - Polar cross correlation is commonly used for determination of ocular torsion from
      video images, but breaks down at eccentric positions if the spherical geometry of
      the eye is not considered. We have extended this method to allow three
      dimensional eye position measurement over a range of +/- 20 deg by determining
      the correct projection of the eye onto the image plane of the camera. We also
      determine the orientation of the camera with respect to the eye, allowing eye
      position to be represented in appropriate head-fixed coordinates. These
      algorithms have been validated using both in vitro and in vivo measures of eye
      position.

PMID- 8746235
TI  - Reading unspaced text is not easy: comments on the implications of Epelboim et
      al.'s (1994) study for models of eye movement control in reading.
AB  - Epelboim, Booth, and Steinman [1994 Vision Research, 34, 1735-1766] recently
      published an article in this journal in which they argued that "unspaced text is
      relatively easy to read" (p. 1760). From this they concluded that the spaces
      between words "are relatively unimportant for guiding reading eye movements" (p.
      1760). We have serious reservations concerning these conclusions. In this letter
      we argue that (1) reading unspaced text is not easy for most readers and (2)
      there are more diagnostic ways to examine the role of spacing. We also comment on
      the implications for models of eye movements in reading.

PMID- 8746236
TI  - Ideal observer for heading judgments.
AB  - Several aspects of the viewing situation affect the ability to determine heading
      from optical flow. These include the amount of depth variation and number of
      texture elements in the scene, the location and amount of the visual field
      stimulated, and the position of the focus of expansion within the stimulus.
      Without a quantification of the discrimination information provided by the
      stimuli presented to the observer, it is impossible to determine how much of an
      observed change in performance reflects the properties of neural mechanisms and
      strategies employed by the observer. To enable a better quantification, we
      developed an ideal observer for the discrimination of heading from random-dot
      flow fields. Internal noises of the ideal observer were set by the results of
      single-dot velocity discrimination experiments. We compared human and ideal
      observer performance in discriminating headings with different patterns of flow
      (e.g. radial vs laminar) presented on different parts of the retina. Efficiency-
      the ratio of ideal and human thresholds--was fairly constant for the various flow
      patterns and retinal eccentricities. This outcome indicates that most of the
      variation in human observers' ability to estimate heading from the flow patterns
      and retinal loci considered here is due to changes in the discrimination
      information provided by the stimulus after measurement by the visual system. In
      the discussion, we show how the ideal observer can be used to quantify the
      spatial distribution of heading discrimination information for any observer
      translation through any scene represented by dots.

PMID- 8746237
TI  - Relative dispersion analysis enhances perimetric sensitivity.
AB  - Objective identification of minor visual field defects is problematic. A possible
      solution is to examine spatial correlations by means of relative dispersion
      analysis, a tool of fractal analysis. We studied patients with glaucoma, previous
      optic neuritis, chiasmal compression and lesions of the brain hemispheres, using
      high-pass resolution perimetry. One-hundred visual field records were drawn
      consecutively for each category and ranked according to severity of defects.
      Records with scores ranking below the 35th percentile, i.e. those with the
      smallest field defects, were analysed. Relative dispersion analysis recognized
      1.3-2.4 times more abnormal subjects than did pattern standard deviation. A
      previously described form index was intermediate in sensitivity. Specificity was
      96%. Relative dispersion analysis appears to capture a novel aspect of visual
      field abnormality, with good sensitivity and specificity. The analysis is easily
      performed.

PMID- 8746238
TI  - Magnetic and electrical brain responses to chromatic contrast in human.
AB  - Differences between magnetic responses to red-green chromatic gratings and yellow
      black luminance gratings were: (1) response waveforms differed considerably; (2)
      at some recording sites the chromatic grating response was considerably greater
      than the sum of responses to the red and green components of the chromatic
      grating; (3) the latencies of the successive peaks in the response to the onset
      of chromatic contrast were greater than the latencies of the corresponding peaks
      in the response to luminance contrast onset; (4) chromatic grating responses were
      lowpass with respect to spatial frequency while luminance grating responses were
      bandpass; (5) chromatic grating responses attenuated more steeply with increasing
      frequency above 2 c/deg than did luminance grating responses. Items (3)-(5) above
      are consistent with well-known psychophysical findings that contrast sensitivity
      is lowpass for chromatic gratings and chromatic responses are more sluggish than
      luminance responses. In subsidiary experiments we found that magnetic responses
      to red-green and blue-yellow equiluminant gratings had similar waveforms in all
      six subjects tested, but the topographical distributions were different in three
      subjects. The results of comparing magnetic and electrical responses to the onset
      and offset of contrast can be understood in terms of the considerable
      intersubject variability in the relation between neuroanatomy and cortical
      function that has been demonstrated by other techniques.

PMID- 8746239
TI  - Disproportionate distribution of field potentials across the toad's tectal visual
      map in response to diffuse light ON and OFF stimulations.
AB  - In toads Bufo marinus and Bufo bufo spinosus, field potentials (FPs) were
      recorded from the surface of the optic tectum at different sites of the visual
      map in response to a sudden diffuse darkening (OFF) and lightening (ON) of the
      visual field of the contralateral eye. The OFF and ON responses were differently
      pronounced or even failed to occur. The latency of the former was significantly
      less than the one of the latter. FP amplitudes of the OFF and ON responses were
      strongest in the representation of a horizonto-superior anterio-lateral portion
      of the visual field and weakest toward the posterior field of vision. This
      phenomenon suggests various interpretations for subsequent experiments.

PMID- 8746240
TI  - The binocular computation of visual direction.
AB  - How is a single visual direction assigned to a binocular feature for which the
      left and right eyes are signaling different directions? According to geometrical
      principles, binocular visual direction is the average of the visual directions
      measured from the left and right eyes. Contrary to this prediction, we have found
      that the relative visual direction between two Gabor targets presented at
      different stereoscopic depths could be manipulated by varying the contrast ratio
      between the left and right images. This finding is consistent with a new model in
      which the relative alignment of depth features is determined from a maximum
      likelihood combination of the direction signals from the left and right eyes. In
      a second experiment we provide support for this model, showing that the magnitude
      of the contrast-dependent bias in visual direction is predicted by the
      uncertainty for spatial localization in the left and right images. Lastly we show
      that visual direction and stereopsis have different dependencies on interocular
      contrast differences, suggesting that the computation of stereo depth and visual
      direction are mediated via different mechanisms.

PMID- 8746241
TI  - Temporal aspects of binocular slant perception.
AB  - We investigate temporal aspects of binocular slant perception in the presence and
      absence of a visual reference. Subjects judge slant induced by large-field
      stereograms of which one half-image is either horizontally scaled or sheared
      relative to the other half-image. Each stimulus is presented for different
      observation periods ranging from 0.1 to 19.2 sec. We quantitatively corroborate
      earlier findings that perceived slant develops significantly faster and to higher
      levels with visual reference than without it. In daily life, when we are active,
      there will not be much time for slant to develop. We find that if observation
      periods are brief (a few seconds or less) slant is poorly perceived if there is
      no visual reference. We conclude that the visual system is relatively insensitive
      to large-field horizontal scale and shear.

PMID- 8746242
TI  - Localizing contours defined by more than one attribute.
AB  - Two experiments were run in order to test how information from different
      attributes is combined to localize contours. In Expt 1 the apparent position of a
      contour defined by one attribute was measured while a contour defined by another
      attribute was presented beside it. Interactions were found between all pairings
      of luminance, color, motion and texture. These results suggested that the
      information associated with each contour is integrated at a common site. In Expt
      2 the precision of localization was measured for contours defined by one, two or
      three attributes (combinations of luminance, color and texture). The improvement
      in precision with additional attributes again supported an integration of contour
      information at a common site prior to a decision of localization.

PMID- 8746243
TI  - Retinal illuminance and contrast sensitivity in human infants.
AB  - Several investigators have related infants' low contrast sensitivity to
      immaturities in the optics and receptor lattice of the immature eye. A critical
      element in the modeling is how much the lower photon catch of the immature retina
      reduces sensitivity; the assumptions vary from square-root to Weber's law and
      lead to very different modeling outcomes. We measured the relationship between
      retinal illuminance and contrast sensitivity at different spatial frequencies.
      The sweep visual-evoked potential was used to measure thresholds in 2- and 3
      month olds and adults over a 2.5-log-unit range of illuminances. The contrast
      threshold vs illuminance functions were fit by power functions. The best-fitting
      exponents for adults were about -0.5 at higher spatial frequencies (consistent
      with square-root law) and lower at lower frequencies. The best-fitting exponents
      for 2- and 3-month olds were -0.2 to -0.35 which indicates that threshold is less
      affected by changes in illuminance than is the case in adults. These results
      suggest that none of the models relating optical and receptoral immaturities to
      infants' spatial vision has assumed an appropriate relationship between lower
      photon catch and contrast sensitivity. Once the models are modified to
      incorporate the relationship obtained in the present experiment, the predictions
      fall well short of explaining 2-month olds' low contrast sensitivity.

PMID- 8746244
TI  - Motion capture and visual attention: comments on Culham and Cavanagh (1994)

PMID- 8746245
TI  - The development of gaze control and predictive tracking in young infants.
AB  - Eye and head tracking of an oscillating visual flow was studied in 1-, 2-, and 3
      month-old infants using EOG and an opto-electronic system. A pronounced decrease
      in phaselag of gaze velocity was observed over this age period, from 170 to 70
      msec, but gain changed only marginally. Latency of the onset of tracking
      decreased with age from 860 to 560 msec. During tracking, the velocity of the
      head showed high frequency components in the 1-6 Hz range, to which the eye
      movements were reciprocal and without systematic phase lag. This coordination
      improved with age.

PMID- 8746246
TI  - Accommodative vergence is driven by the phasic component of the accommodative
      controller.
AB  - Conflicting opinions exist as to whether the phasic (reflex) component alone or
      both the phasic and tonic (adaptive) components of the accommodation and vergence
      systems drive accommodative vergence and vergence accommodation crosslinks. In
      this study the dissociated phoria to a 2 D target was measured before and after
      accommodative adaptation to discriminate the two possibilities. Results showed a
      significant difference in the dark-focus of accommodation pre- and post-near
      vision task, indicating that accommodative adaptation had occurred. No
      significant change occurred in dark-vergence or in the accommodative response to
      the 2 D target. However, a significant decrease was found in the dissociated
      phoria presumably because of decreased phasic accommodation and its stimulation
      of accommodative vergence after the adaptation. This result is consistent with a
      model in which the accommodative vergence crosslink is driven by phasic
      accommodation only.

PMID- 8746247
TI  - Fast disconjugate adaptations of saccades in microstrabismic subjects.
AB  - In normal subjects, saccade amplitude inequality can be induced almost
      immediately when the image is made larger for one eye. This disconjugacy allows
      binocular fusion at the point of regard despite the image size inequality. It
      persists under subsequent monocular viewing which suggests a fast adaptive
      mechanism. This study tests whether such disconjugacy can be induced in subjects
      with microstrabismus who do not have foveal fusion. Three microstrabismic
      subjects viewed a random dot pattern the size of which was 10% larger in one eye.
      Within 40 sec horizontal saccades became larger in the eye viewing the larger
      image by 4-10%; the induced disconjugacy persisted under subsequent monocular
      viewing. Thus, fast disconjugate adaptation is possible in microstrabismus
      demonstrating that foveal fusion is not necessary to achieve it.

PMID- 8746248
TI  - The abutting grating illusion.
AB  - Two line gratings abutting each other with a phase shift of half a cycle elicit
      the perception of an illusory line running orthogonally between the two sets of
      grating lines. We found that rating strength increases with increasing number of
      lines, line length, and phase angle. In contrast, rating strength decreases with
      increasing spacing of lines, lateral misalignment, rotation of one grating
      relative to the other, and line width. There is a pronounced oblique effect at 45
      deg when the orientation of the abutting gratings is changed from horizontal
      through diagonal to vertical. Findings are interpreted in terms of a
      neurophysiological model. We conclude that the end-stopped receptive fields
      activated by the grating lines are about 6 deg long and 2 deg wide. On the other
      hand, the "response fields" of the cells, integrating orthogonally across line
      ends, are assumed to be 5 deg long and less than 1 deg wide. The psychophysical
      data compare favorably with available neurophysiological data in Area V2 of the
      macaque suggesting that the perception of illusory contours in human observers
      may be based on cortical cell properties similar to those found in the monkey.

PMID- 8746249
TI  - A cell model for the detection of local image motion on the magnocellular pathway
      of the visual cortex.
AB  - We propose that five types of cell on the magnocellular pathway of the visual
      cortex constitute a function hierarchy for detecting local image motion. Lateral
      geniculate nucleus cells and two simple cell types analyse one-dimensional
      velocities perpendicular to oriented components within a moving stimulus.
      Combining these velocities, a group of complex cells along a sine wave fire over
      the cell array. The amplitude and phase of the wave correspond to the local
      motion's speed and direction. A motion-detection cell in the middle temporal area
      then extracts the wave of activated complex cells to detect the motion. Applying
      Hough and inverse Hough transforms and Reichardt's spatio-temporal correlation to
      the hierarchy, we modeled these cell types as a series of formulas that represent
      the synaptic functions of neurons. The modeled cells reflect the response to
      various stimuli in actual cells, and explain Adelson and Movshon's two-stage
      hypothesis neurophysiologically. The intersection-of-constraint-lines solution of
      the hypothesis is equivalent to the inverse Hough transform processed in motion
      detection cells. We propose tests for validating this cell model using
      microelectrodes and optical imaging.

PMID- 8746250
TI  - Cortical dynamics of form and motion integration: persistence, apparent motion,
      and illusory contours.
AB  - How does the visual system generate percepts of moving forms? How does this
      happen when the forms are emergent percepts, such as illusory contours or
      segregated textures, and the motion percept is apparent motion between the
      emergent forms? We develop a neural model of form-motion interactions to explain
      and simulate parametric properties of psychophysical motion data and to make
      predictions about how the parallel cortical processing streams V1-->MT and V1-
      >V2-->MT control form-motion interactions. The model explains how an illusory
      contour can move in apparent motion to another illusory contour or to a luminance
      derived contour; how illusory contour persistence relates to the upper
      interstimulus interval (ISI) threshold for apparent motion; and how upper and
      lower ISI thresholds for seeing apparent motion between two flashes decrease with
      stimulus duration and narrow with spatial separation (Korte's laws). The model
      accounts for these data by suggesting how the persistence of a boundary
      segmentation in the V1-->V2 processing stream influences the quality of apparent
      motion in the V1-->MT stream through V2-->MT interactions. These data may all be
      explained by an analysis of how orientationally tuned form perception mechanisms
      and directionally tuned motion perception mechanisms interact.

PMID- 8746251
TI  - Contrast sensitivity in one-eyed subjects.
AB  - The effects of early monocular form deprivation on the developing mammalian
      visual system, and the anatomical and physiological consequences of early
      monocular enucleation, suggest that the remaining eye of human subjects who had
      the other eye removed early during development might be capable of supernormal
      performance. To test this inference, the achromatic contrast sensitivity of the
      remaining eye of subjects who had the other eye removed at different ages after
      birth was compared with that of normal subjects tested under monocular and
      binocular conditions. The results show that all subjects who had an eye removed
      during early development had a higher contrast sensitivity than the better eye of
      control subjects. Furthermore, the earlier in development that the eye was
      removed, the lower the spatial frequency at which contrast sensitivity is
      enhanced compared with measurements made in the better eye of control subjects,
      and the larger the range of spatial frequencies over which contrast sensitivity
      is supernormal.

PMID- 8746252
TI  - Is the motion system relatively spared in amblyopia? Evidence from cortical
      evoked responses.
AB  - Visual evoked potentials (VEPs) produced by pattern reversal were compared with
      those elicited by onset of motion in 37 amblyopic children (20 with anisometropic
      amblyopia, seven with strabismic amblyopia and 10 with both anisometropia and
      strabismus). The amplitudes and peak latencies of the main P1 peak in the pattern
      reversal VEP and of the motion-specific N2 peak in the motion-onset VEP through
      the amblyopic eye were compared with those through the normal fellow eye.
      Regardless of the type of amblyopia, the amplitude of the pattern-reversal VEP
      for full-field stimulation was significantly smaller and its latency
      significantly longer through the amblyopic eye (P < 0.001). In contrast, neither
      the amplitudes nor the latencies of the N2 motion-onset VEPs differed
      significantly between amblyopic and non-amblyopic eyes. For pattern-reversal VEPs
      through the amblyopic eyes, the extent to which amplitude was reduced and latency
      prolonged correlated well with the reduction of visual acuity, whereas the
      amplitudes and latencies of motion-onset VEPs did not vary with visual acuity.
      Even for stimuli restricted to the central visual field (5 or 2 deg diameter) or
      to the peripheral field (excluding the central 5 deg), motion-onset responses
      were indistinguishable through the two eyes, while pattern-reversal responses
      always differed significantly in amplitude. These results suggest that the source
      of motion-onset VEPs (probably an extrastriate motion-sensitive area) is less
      affected in amblyopia than that of pattern-reversal VEPs (probably the striate
      cortex). The motion pathway, presumably deriving mainly from the magnocellular
      layers of the lateral geniculate nucleus, may be relatively spared in amblyopia.

PMID- 8746253
TI  - Infrared imaging of sub-retinal structures in the human ocular fundus.
AB  - The interaction of infrared light with the human ocular fundus, particularly sub
      retinal structures, was studied in vivo. Visible and infra-red wavelengths and a
      scanning laser ophthalmoscope were used to acquire digital images of the human
      fundus. The contrast and reflectance of selected retinal and sub-retinal features
      were computed for a series of wavelengths or modes of imaging. Near infrared
      light provides better visibility than visible light for sub-retinal features. Sub
      retinal deposits appear light and thickened; the optic nerve head, retinal
      vessels, and choroidal vessels appear dark. Contrast and visibility of features
      increases with increasing wavelength from 795 to 895 nm. Optimizing the mode of
      imaging improves the visibility of some structures. This new quantitative basis
      for near infrared imaging techniques can be applied to a wide range of imaging
      modalities for the study of pathophysiology and treatment in diseases affecting
      the retinal pigment epithelium and Bruch's membrane, such as age-related macular
      degeneration.

PMID- 8746254
TI  - A surgeon with HIV.

PMID- 8746255
TI  - Managing contact dermatitis.

PMID- 8746256
TI  - Who needs carotid endarterectomy?

PMID- 8746257
TI  - Using your experience in the MEQ exam.

PMID- 8746258
TI  - Cochlear implants: a modern miracle.

PMID- 8746259
TI  - Options for treating otitis media.

PMID- 8746260
TI  - Rhinitis: common, debilitating and treatable.

PMID- 8746261
TI  - A realistic view of sinusitis.

PMID- 8746262
TI  - Preparing for the mouth cancer epidemic.

PMID- 8746263
TI  - The role of glutathione S-transferases in head and neck squamous cell
      carcinogenesis.

PMID- 8746264
TI  - Metastatic tumours to the oral region. An overview.
AB  - Metastatic tumours to the oral region are uncommon. There are more published
      cases of jawbone metastases than in oral soft tissues. The most common primary
      sources of metastatic tumours to the oral region are the breast, lung, kidney,
      bone and colon. The breast is the most common primary site for tumours
      metastasising to the jawbones, whereas the lung is the most common source for
      metastases to the oral soft tissues. In the jawbones, the common location of the
      metastatic lesions is the mandible, with the molar area being the most frequent
      involved site. In the oral soft tissues, the attached gingiva is the most common
      affected site followed by the tongue. In nearly 30% of cases, the metastatic
      lesion in the oral region is the first indication of an undiscovered malignancy
      at a distant site. The biological basis of the metastatic process is discussed.

PMID- 8746265
TI  - The Thomsen-Friedenreich (T) simple mucin-type carbohydrate antigen in salivary
      gland carcinomas.
AB  - The simple mucin-type T (Thomsen-Friedenreich) antigen is a marker of carcinomas,
      and has been related to aggressiveness of malignant tumours. We studied the
      expression of T, sialosyl-T, A and H blood group antigens in salivary gland
      carcinomas. The aim was to study whether the tumours, based on the expression of
      these structures, could be divided into new diagnostic groups that may later show
      prognostic significance. Formalin fixed paraffin-embedded tissue sections from 77
      salivary gland carcinomas of different histological types were studied using
      immunohistology and monoclonal antibodies (MAbs). Fresh frozen tissue was
      examined in 30 of the cases. Frozen sections were superior to paraffin sections
      in demonstrating T and H antigens. Aberrant glycosylation with accumulation of T
      (in cytoplasm) and sialosyl-T antigens (in cytoplasm, membrane and mucin) was
      found in all tumour types except acinic cell carcinomas. In carcinomas in
      pleomorphic adenomas (CinPA) the effect of fixation was minimal and T antigen
      location was different. In carcinomas with myoepithelial cell (MEC)
      participation, the MECs had retained a normal glycosylation pattern. H antigen
      was expressed in all tumour types, except acinic cell carcinomas and CinPA. A
      antigen was expressed in all tumour types from blood group A patients, except in
      CinPA. The expression of T, sialosyl-T, H and A antigens in relation to
      differentiation grade varied with tumour type in poorly differentiated areas.
      High and moderate differentiated areas were always stained, whereas poorly
      differentiated areas in some tumour types expressed T and sialosyl-T antigens and
      others did not. The accumulation versus lack of expression of the investigated
      structures in poorly differentiated areas of the tumours may be of prognostic
      significance.

PMID- 8746266
TI  - Continuous hyperfractionated accelerated radiotherapy in the treatment of
      carcinoma of the columella and vestibule of the nose.
AB  - Twenty-one patients with squamous cell carcinoma of the nasal columella and
      vestibule were treated at the Mount Vernon Centre for Cancer Treatment between
      March 1986 and January 1994. Tumours ranged from 15 to 55 mm in maximum dimension
      (median 25 mm). All patients were treated with radical intent with continuous
      hyperfractionated accelerated radiotherapy (CHART). This group was analysed with
      respect to tumour control, tumour cell kinetics and radiation-induced morbidity
      at a median time to last follow-up of 40 months. Particular attention was paid to
      the detailed evaluation of late radiation changes. Patients who were still alive
      were assessed as to the satisfaction with the cosmesis of their treated nose.
      Four patients had relapse of disease either at the primary site alone (2), in
      neck nodes (1) or in both regions (1). One patient was successfully salvaged with
      surgery. Cell kinetic studies showed that cancers at this site may have potential
      for rapid cellular repopulation similar to cancers developing at other head and
      neck sites. CHART was well tolerated by patients. Late skin changes were
      remarkedly slight (despite full skin dose) and overall cosmesis excellent with
      this radiotherapy schedule.

PMID- 8746267
TI  - A retrospective study of the use of cisplatinum-5-fluorouracil neoadjuvant
      chemotherapy in cervical-node-positive nasopharyngeal carcinoma (NPC).
AB  - A retrospective study on 422 nasopharyngeal carcinoma (NPC) patients with
      cervical nodal metastases treated between 1984 and 1987 was performed. 169
      received neoadjuvant chemotherapy (CHEMO) with cisplatinum and 5-fluorouracil for
      two or three courses prior to definitive radiotherapy and 253 were treated by
      radical radiotherapy alone (NCHEMO). While the primary tumour (T-stage)
      prognosticators had been comparable between the two groups, CHEMO had
      significantly more advanced cervical nodal metastases with bulkier nodes and more
      low-cervical and supraclavicular nodes (P < 0.05) which could account for its
      overall worse survival, poorer regional tumour control and a trend towards worse
      systemic tumour control. The worse regional control in CHEMO for Ho's N1 could be
      the result of more bulky nodes and more tumours infiltrating the skull base
      and/or causing cranial nerve(s) palsy. There was no statistical or apparent
      difference between CHEMO and NCHEMO for the same Ho's overall stages of NPC with
      comparable nodal and primary tumour characteristics for the clinical endpoints of
      actuarial survival rate (ASR), disease-free survival rate (DFS), free of local
      failure survival rate (FLF), and free from distant metastases survival rate
      (FDM), despite the presence of significantly more fixed nodes and bulky nodes.
      This suggests a possible beneficial effect of the neoadjuvant chemotherapy.
      However, multivariate analysis has not shown the administration of the
      neoadjuvant chemotherapy to be of prognostic significance. Even though the
      chemotherapy was well tolerated with little toxicity, we recommend against the
      routine use of neoadjuvant chemotherapy in cervical-node-positive NPC outside the
      context of a prospective randomised clinical trial.

PMID- 8746268
TI  - Apoptosis in normal epithelium, premalignant and malignant lesions of the
      oropharynx and oral cavity: a preliminary study.
AB  - To explore the involvement of apoptosis in the development of oral and
      oropharyngeal squamous cell carcinoma (SCC) in vivo, biopsies were taken from
      patients with macroscopically normal (n = 6), leukoplakic (n = 12) or malignant
      (n = 8) mucosa. Leukoplakic lesions were divided histologically into dysplasia (n
      = 5) or carcinoma in situ (CIS: n = 7). Material was prepared for light and
      electron microscopy. The apoptotic index (AI), vertical cell position of
      apoptoses (cp), mitotic index (MI) and AI:MI ratio were calculated for each
      patient. AI increased from 0.12% +/- 0.07 S.E.M. (normal) to 0.58 +/- 0.13 (CIS)
      but fell to 0.14 +/- 0.14 in SCC. Apoptoses were suprabasal in normals, but
      generalised in CIS. MI increased from normal (0.20 +/- 0.06) to SCC (0.32 +/-
      0.09), and AI:MI was at its maximum in CIS (1.57; SCC: 0.44). The results suggest
      that a change in apoptosis accompanies the onset of invasion in a premalignant
      lesion of the human oral cavity and oropharynx.

PMID- 8746269
TI  - Differential c-myc, c-jun, c-raf and p53 expression in squamous cell carcinoma of
      the head and neck: implication in drug and radioresistance.
AB  - The expression of oncogenes c-myc, c-jun and c-raf and tumour suppressor gene p53
      was assessed by northern blot analysis of 42 tumours and p53 protein expression
      by immunohistochemistry on paraffin-embedded sections from 36 specimens of
      squamous cell carcinoma of the head and neck (SCCHN) obtained before therapy. Of
      the 42 tumours, 89, 100 and 100% expressed c-myc, c-jun and c-raf oncogenes,
      respectively. These oncogene expressions did not correlate with sex, age or
      clinical stage of the disease. However, an association was found between low c
      myc expression (P = 0.0001) and high c-jun expression (P = 0.0001) and absence of
      tumoral response to neoadjuvant chemotherapy. On the other hand, c-raf
      overexpression was observed in patients resistant to radiation therapy (P =
      0.0494). Forty-two per cent of the tumours showed p53 protein overexpression,
      which did not correlate with any clinical parameter. This p53 protein
      overexpression was associated with high p53 mRNA levels (REL) (P = 0.0223). A
      correlation was found between increased c-myc RNA expression and lack of p53
      protein expression (P = 0.0407). In addition, a lack of p53 protein expression
      was indicative of tumour relapse (P = 0.05). None of these biological parameters
      were associated with disease-free survival (Cox-Mantel test). In conclusion, the
      overexpression of c-myc, c-jun and c-raf may be independently associated to
      tumoral response to chemotherapy or radiotherapy, or to tumour relapse, but fail
      to predict long-term survival.

PMID- 8746270
TI  - Value of p53 expression in oral cancer and adjacent normal mucosa in relation to
      the occurrence of multiple primary carcinomas.
AB  - Paraffin embedded, formalin fixed tissue sections from patients suffering from a
      primary oral squamous cell carcinoma were immunohistochemically investigated for
      the presence of p53 expression using the Bp53-11 antibody. The aim of this study
      was to determine the predictive value of p53 expression as a biomarker for the
      development of a second primary tumour (SPT) in the respiratory and upper
      digestive tract. In a nested case control study, neoplastic and normal tissue
      sections of 44 patients who had a previous history of cancer were used. 15 of the
      44 had developed a SPT, while the other 29 were minimally 7 years free of
      disease. Additionally, nine SPTs were included in this study to establish whether
      concordance exists in tumours that develop in the same field. 10 of the 29
      patients (34%) free of tumour during follow-up had p53 positive tumours. 8 of 15
      patients (53%) who developed a SPT had a p53 positive primary tumour. This
      difference is not statistically different (chi 2-test). Forty percent of the
      total group of primary oral cavity tumours showed p53 positivity. When comparing
      the first and the second tumours, discordance in p53 expression between the first
      and second tumours was seen in 4 out of 9 cases. None of the cases showed p53
      positivity in adjacent normal mucosa. In conclusion, p53 immunoreactivity in
      neoplasia, dysplasia and normal tissue does not predict the development of a SPT.
      In addition, multiple primary tumours do not have identical p53 expression.

PMID- 8746272
TI  - ras mutations are uncommon in nasopharyngeal carcinoma.

PMID- 8746271
TI  - A proposal for a classification and staging system for oral leukoplakia: a
      preliminary study.
AB  - A classification and staging system for oral leukoplakia is proposed based on the
      recently revised definition of this premalignant lesion. The initial experiences
      of this system are described on the basis of 100 patients with oral leukoplakia.
      The new classification and staging system seems very suitable for characterizing
      groups of patients with oral leukoplakia. Whether this system is also valuable
      with regard to guidelines for management of these patients has still to be
      proven.

PMID- 8746273
TI  - A phase I/II study on hyperfractionated chemoradiation using chemotherapy as part
      of each fraction of treatment in locally far advanced head and neck cancer.

PMID- 8746274
TI  - PCNA and p53.

PMID- 8746275
TI  - A reader's guide to the medical literature--an introduction.

PMID- 8746277
TI  - A reader's guide to the evaluation of prognostic studies.
AB  - In this article, we review guidelines which may be used to evaluate studies
      documenting prognosis. We describe a clinical problem involving the prognosis of
      a patient in an intensive care unit. An approach to the literature search is then
      outlined. The results of the literature search are described and criteria for the
      appraisal of articles describing prognosis and prognostic factors are discussed
      using one article as an example.

PMID- 8746276
TI  - A role for the Fas antigen in lupus?

PMID- 8746278
TI  - Asthma.
AB  - Bronchial asthma is now recognised to be a major cause of morbidity and even
      mortality in people of all ages. Two important ideas have changed our approach to
      asthma management. The first is understanding that asthma is a chronic
      inflammatory disorder which needs regular treatment with anti-inflammatory drugs
      such as inhaled corticosteroids to prevent further attacks. The second
      development is the availability of prescribable peak flow meters, which allows
      both confident diagnosis and early prediction of relapse. Asthma management
      guidelines provide a logical treatment framework for most patients, but a few
      difficult cases still consume large amounts of medical time. The commonest
      problem is one of compliance with treatment which may respond to patient
      education, although this is not universally so. Other problems include
      misdiagnosis, acid reflux and, rarely, true corticosteroid-resistant asthma.
      Several potentially important new treatments have been developed. These include
      longer acting anticholinergic drugs, drugs with bronchodilator and some anti
      inflammatory properties which antagonise or inhibit the production of
      leukotrienes, sub-types of phosphodiesterase inhibitor with anti-inflammatory
      properties and immunosuppressive drugs such as cyclosporin. Ultimately these new
      treatments must be rigorously tested and integrated into a care plan that remains
      centred on patient education.

PMID- 8746279
TI  - Clinical guidelines and their implementation.
AB  - Within the UK there has been increasing interest in the development and
      implementation of guidelines, as the emphasis on clinical effectiveness is
      gathering momentum. This paper outlines some of the practical issues encountered
      in developing and implementing guidelines, based on experiences within Liverpool.
      Developing local guidelines can be a lengthy process, but that process is not a
      waste of time if it means there is more likely to be compliance in the end.
      Dissemination of guidelines alone is not enough; it needs to be combined with an
      appropriate implementation strategy. There is a danger of primary care being
      overloaded with new guidelines; there needs to be a timed strategy for their
      introduction. More imaginative thought needs to be put into the marketing of new
      ideas in order to change practice. We need to encourage the ethos amongst
      healthcare professionals of expecting to have to constantly update knowledge and
      practice.

PMID- 8746280
TI  - Venepuncture: the medicolegal hazards.
AB  - Venepuncture is commonly regarded as a trivial procedure allocated to the most
      junior medical staff. The result of this policy is that junior doctors are
      required to perform a minimally invasive procedure on consenting patients without
      any structured venepuncture training or assessment. Consequently, inexperienced
      doctors may perform multiple and sometimes unnecessary, venepunctures, which
      could damage essential venous access, eg, in the diabetic or renal patient. We
      review the medicolegal position and suggest that structured venepuncture training
      is essential and argue that unskilled treatment may be regarded by the Courts as
      demonstrating the mens rea of assault in the form of recklessness.

PMID- 8746281
TI  - Discussing the diagnosis and prognosis with cancer patients.
AB  - Effective doctor-patient communication is an integral part of good clinical care.
      Telling a patient that he/she has cancer can be a daunting task. If done with
      empathy and sensitivity it can create an important bond between the doctor and
      patient. If done brusquely and without tact it can create barriers and lasting
      hostility. Several key steps help make the breaking of bad news easier for
      doctors and patients. There is not one 'right formula' but appreciation of and
      responsiveness to the patient's verbal and non-verbal signals are core skills
      which can be developed.

PMID- 8746282
TI  - HIV medicine: drug side effects and interactions.
AB  - The drugs used in HIV medicine often have toxic side effects; additionally, the
      risk of drug interactions is high because of the frequent necessity to prescribe
      multiple drugs. This article covers common or important drug side effects and
      interactions.

PMID- 8746283
TI  - Routine nasal surgery: an audit of outpatient follow-up.
AB  - The study objective was to assess the value of outpatient follow-up of patients
      who undergo routine uncomplicated nasal surgery. A total of 177 postoperative
      patients (117 males, 60 females) undergoing routine nasal surgery at the Raigmore
      Hospital, Inverness, was selected over a six-month period, 92 of whom (60 males,
      32 females) were requested to return to the clinic for a follow-up session. A
      total of 72 (78.3%) patients attended for post-operative review. Of these, 55
      patients (76.4%) had achieved a satisfactory result from surgery and 17 (23.6%)
      required additional treatment for persistent problems. The former group were
      pleased with the outcome of their operation and required no further treatment. Of
      the 25 patients who were prescribed medication at the time of discharge from
      hospital, 19 (76.0%) were still complying with the medication and required no
      further specialist assistance. The results suggest that routine follow-up of
      uncomplicated cases of nasal surgery is unnecessary. The good therapeutic results
      in the majority of cases indicate a need to decrease the number of routine
      reviews to reduce the high non-attendance rate and increase the proportion of new
      patients seen at outpatient clinics. The role played by general practitioners is
      vital to this cause. This would include minor postoperative care, monitoring of
      prescribed medication and review of patients with occasional postoperative
      problems.

PMID- 8746284
TI  - Vasculitis and rapidly progressive glomerulonephritis in the elderly.
AB  - The proportion of patients with vasculitis and rapidly progressive nephritis aged
      70 years or over has risen from about 10% in the 1980s to over 30% in series
      reported in the 1990s. This study was undertaken to examine the presentation and
      outcome of such older patients. Seventeen of 56 patients (30%) who presented at
      two renal units were aged 70 years or over. Mean creatinine level at presentation
      was 530 mumol/l, and five patients received dialysis at presentation. Outcome was
      dependent on three factors, namely comorbid pathology, response to
      immunosuppressive therapy, and the occurrence in three cases of temporary
      spontaneous partial remission. Overall patient survival at one and two years was
      62.5% and 50%, respectively, and 90% and 100% of surviving patients were
      independent of dialysis at one and two years, respectively. Response to
      chemotherapy was excellent, with full rehabilitation in many cases and no deaths
      directly attributable to adverse effects of immunosuppressive therapy. We
      conclude that diagnosis of vasculitis and rapidly progressive glomerulonephritis
      by renal biopsy and the subsequent administration of chemotherapy (including
      cyclophosphamide in many cases) resulted in a worthwhile benefit in these elderly
      patients.

PMID- 8746285
TI  - A randomised, double-blind, placebo-controlled trial of L-carnitine in suspected
      acute myocardial infarction.
AB  - In a randomised, double-blind placebo-controlled trial, the effects of the
      administration of oral L-carnitine (2 g/day) for 28 days were compared in the
      management of 51 (carnitine group) and 50 (placebo group) patients with suspected
      acute myocardial infarction. At study entry, the extent of cardiac disease,
      cardiac enzymes and lipid peroxides were comparable between the groups, although
      both groups showed an increase in cardiac enzymes and lipid peroxides. At the end
      of the 28-day treatment period, the mean infarct size assessed by cardiac enzymes
      showed a significant reduction in the carnitine group compared to placebo.
      Electrocardiographic assessment of infarct size revealed that the QRS-score was
      significantly less in the carnitine group compared to placebo (7.4 +/- 1.2 vs
      10.7 +/- 2.0), while serum aspartate transaminase and lipid peroxides showed
      significant reduction in the carnitine group. Lactate dehydrogenase measured on
      the sixth or seventh day following infarction showed a smaller rise in the
      carnitine group compared to placebo. Angina pectoris (17.6 vs 36.0%), New York
      Heart Association class III and IV heart failure plus left ventricular
      enlargement (23.4 vs 36.0%) and total arrhythmias (13.7 vs 28.0%) were
      significantly less in the carnitine group compared to placebo. Total cardiac
      events including cardiac deaths and nonfatal infarction were 15.6% in the
      carnitine group vs 26.0% in the placebo group. It is possible that L-carnitine
      supplementation in patients with suspected acute myocardial infarction may be
      protective against cardiac necrosis and complications during the first 28 days.

PMID- 8746286
TI  - Enterococcal endocarditis after extracorporeal shock wave lithotripsy for
      nephrolithiasis.
AB  - We report a case of enterococcal endocarditis following extracorporeal shock wave
      lithotripsy (ESWL) for ureteral stone. Although endocarditis following ESWL is
      very rare, transient bacteraemia occurs during ESWL. This case is a reminder that
      enterococcal endocarditis may follow innovative genitourinary procedures without
      appropriate prophylaxis.

PMID- 8746287
TI  - The effects of octreotide in a patient with Nelson's syndrome.
AB  - We have administered octreotide, 100 micrograms tid, to a 27-year-old man with
      Nelson's syndrome. After seven days of therapy, adrenocorticotropin levels fell
      to 54% of initial values, and some shrinkage of the tumour was observed. This
      study indicates that octreotide therapy may have a role in the treatment of
      Nelson's syndrome.

PMID- 8746288
TI  - Incidental mucinous cystadenocarcinoma of the appendix.
AB  - The incidental finding of a rare appendiceal tumour in a previously healthy male
      patient is described. He presented as an emergency with a self-inflicted
      abdominal stab injury. At laparotomy, there was no visceral damage but the
      appendix was hugely distended and appendectomy was performed. Subsequent
      histological examination of the appendix revealed a low-grade mucinous
      cystadenocarcinoma. A right hemicolectomy was performed two months later which
      demonstrated no residual tumour.

PMID- 8746289
TI  - Massive haemorrhage due to colitis secondary to nonsteroidal anti-inflammatory
      drugs.
AB  - A case of massive haemorrhage due to colitis induced by nonsteroidal anti
      inflammatory drugs in a 74-year-old man is reported.

PMID- 8746290
TI  - Abdominal tumours and neurofibromatosis.

PMID- 8746291
TI  - Headache and visual disturbance.

PMID- 8746292
TI  - Cigarette smoking: an epidemiological overview.
AB  - The detailed mortality and morbidity statistics on smoking tend to conceal the
      overall impact of the habit on health. About 3 million people die each year from
      smoking in economically developed countries, half of them before the age of 70.
      Cancers of eight sites are recognized as being caused by smoking--lung cancer
      almost entirely and the others (upper respiratory, bladder, pancreas, oesophagus,
      stomach, kidney, leukaemia) to a substantial extent. Six other potentially fatal
      diseases are also judged to be caused by smoking: respiratory heart disease,
      chronic obstructive lung disease, stroke, pneumonia, aortic aneurysm and
      ischaemic heart disease, the most common cause of death in economically developed
      countries. Non-fatal diseases, such as peripheral vascular disease, cataracts,
      hip fracture, and periodontal disease, which cause appreciable disability, cost
      and inconvenience are also caused by smoking. In pregnancy, smoking increases the
      risk of limb reduction defects, spontaneous abortion, ectopic pregnancy, and low
      birth weight. While there are some diseases for which smoking shows a protective
      effect, the 'benefits' of these are negligible in relation to the illness and
      premature mortality caused by smoking. About 20% of all deaths in developed
      countries are caused by smoking; an enormous human cost which can be completely
      avoided.

PMID- 8746293
TI  - Mortality from smoking worldwide.
AB  - Estimates are made of the numbers and proportions of deaths attributable to
      smoking in 44 developed countries in 1990. In developed countries as a whole,
      tobacco was responsible for 24% of all male deaths and 7% of all female deaths,
      rising to over 40% in men in some former socialist economies and 17% in women in
      the USA. The average loss of life for all cigarette smokers was about 8 years and
      for those whose deaths were attributable to tobacco about 16 years. Trends in
      mortality attributable to tobacco differed between countries. In some the
      mortality in middle age (35-69 years) had decreased by half in men since 1965; in
      others it was continuing to increase. In women, the proportion was mostly
      increasing, almost universally in old age. Mortality not attributable to smoking
      decreased since 1955 in all OECD (Organization for European Collaboration and
      Development) countries, by up to 60% in men and more in women. No precise
      estimate can be made of the number of deaths attributable to smoking in
      undeveloped countries, but the prevalence of smoking suggests that it will be
      large. In the world as a whole, some 3 million deaths a year are estimated to be
      attributable to smoking, rising to 10 million a year in 30-40 years' time.

PMID- 8746294
TI  - Environmental tobacco smoke.
AB  - Environmental tobacco smoke is an important contaminant of indoor air. For a non
      smoker living with a smoker the exposure is equivalent to about 1% of that from
      actively smoking 20 cigarettes a day (based on plasma cotinine). There is strong
      and consistent evidence that passive smoking increases the risk of lung cancer.
      It is estimated that there is an increase in risk of 24% (95% confidence interval
      11-38%) compared to unexposed non-smokers, and several hundred lung cancer deaths
      per year in Britain are attributable to environmental tobacco smoke exposure.
      Passive smoking is associated with an increase in risk of chronic respiratory
      disease in adults of 25% (10-43%), and increases the risk of acute respiratory
      illness in children, by 50-100%. It is likely that passive smoking increases the
      risk of ischaemic heart disease, and that exposure in pregnancy lowers
      birthweight, but there is inconsistency between different estimates of the
      magnitude of risk. The overall hazard is sufficient to justify measures to
      restrict smoking in public places and workplaces, and to discourage people from
      smoking in their homes.

PMID- 8746295
TI  - Cancers weakly related to smoking.
AB  - In 1985, review of the carcinogenic effects of tobacco led the International
      Agency for Research on Cancer to conclude that the smoking of cigarettes was an
      important cause of cancers of the lung, larynx, oro- and hypo-pharynx,
      oesophagus, bladder, renal pelvis, and pancreas and that the smoking of tobacco
      in other form was also an important cause of some of them. More evidence about
      common cancers has now been obtained in cohort studies and about less common
      cancers in case-control studies. Many are weakly related to smoking. Review now
      justifies the conclusion that cigarette smoking is also a cause of cancers of the
      stomach, renal body, liver, and nose and of myeloid leukaemia and may be a cause
      of cancers of the nasopharynx and lip, and that pipe smoking is a cause of cancer
      of the lip. Associations between cigarette smoking and cancers of the large bowel
      and cervix uteri may be largely, and perhaps wholly, explained by confounding.

PMID- 8746296
TI  - Smokeless tobacco.
AB  - Smokeless tobacco practices are common in some parts of the world and the use
      seems to be increasing. Nicotine exposure is similar in smokeless tobacco users
      and smokers, often leading to strong physical dependence. As a rule, smokeless
      tobacco products contain high levels of nitrosamines with carcinogenic potency in
      experimental animals. Habitual use of oral tobacco can increase the risk of oral
      cancer, but the data are insufficient to assess in detail the risks associated
      with many types of smokeless tobacco. A recent study suggests that smokeless
      tobacco use is related to cardiovascular disease, which could be of great public
      health importance. The known and suspected health risks associated with the use
      of smokeless tobacco provide a basis for preventive action. In particular,
      efforts are needed to limit the introduction of such practices among young
      people, which may serve as a gateway to smoking.

PMID- 8746297
TI  - Beneficial effects of nicotine and cigarette smoking: the real, the possible and
      the spurious.
AB  - Cigarette smoking is an established risk factor for cancer and cardiovascular
      disease, and is the leading cause of avoidable disease in most industrialized
      countries. Less well-known are possible beneficial effects, which are briefly
      considered in this survey. Preliminary data suggest that there may be inverse
      associations of smoking with uterine fibroids and endometriosis, and protective
      effects on hypertensive disorders and vomiting of pregnancy are likely. Smoking
      has consistently been found to be inversely related to the risk of endometrial
      cancer, but cancers of the breast and colon seem unrelated to smoking. Inverse
      associations with venous thrombosis and fatality after myocardial infarction are
      probably not causal, but indications of benefits with regard to recurrent
      aphthous ulcers, ulcerative colitis, and control of body weight may well reflect
      a genuine benefit. Evidence is growing that cigarette smoking and nicotine may
      prevent or ameliorate Parkinson's disease, and could do so in Alzheimer's
      dementia. A variety of mechanisms for potentially beneficial effects of smoking
      have been proposed, but three predominate: the 'anti-estrogenic effect' of
      smoking; alterations in prostaglandin production; and stimulation of nicotinic
      cholinergic receptors in the central nervous system. Even established inverse
      associations cannot be used as a rationale for cigarette smoking. These data can
      be used, however, to clarify mechanisms of disease, and point to productive
      treatment or preventive options with more narrowly-acting interventions.

PMID- 8746298
TI  - Women and smoking.
AB  - Smoking kills over half a million women each year and is the most important
      preventable cause of female premature death in several developed countries.
      However, in many countries, cigarette smoking still tends to be regarded as a
      mainly male problem. This paper explores the reasons why more attention needs to
      be paid to issues around smoking and women, even in countries which currently
      have low levels of female cigarette smoking. The article includes an overview of
      current patterns and trends of smoking among women, and the factors which
      influence smoking uptake and cessation in women compared to men. The experience
      of countries with the longest history of widespread female smoking is used to
      identify some of the key challenges facing developed and developing countries.
      Tobacco companies have identified women as a key target group, therefore
      particular attention is given to the ways in which they have attempted to reach
      women through advertising and other marketing strategies. It is concluded that in
      order to halt and ultimately reverse the tobacco epidemic among women, tobacco
      control policies need to encompass both gender-specific and gender-sensitive
      approaches. Examples are given of the types of action that are needed in relation
      to research, public policy and legislation, and education.

PMID- 8746299
TI  - Children and smoking: the family circle.
AB  - Children's and adults' smoking can form a 'family circle'. Young women and their
      male partners who are less well-educated and less affluent are most likely to
      smoke during the woman's pregnancy. The harmful effects on the fetus, including
      low birth weight and increased risk of respiratory diseases, are carried forward
      into childhood. The frequent minor ailments can cause absence from school,
      falling behind with school work and perhaps under-achievement. Children of
      mothers who smoked during pregnancy are likely to have smaller stature which can
      also affect self-esteem. Passive smoking in the home exacerbates these effects
      and adds others. The child, therefore, can become disenchanted with school and
      reject its norms and is then at increased risk of becoming a smoker. These young
      smokers are most likely to leave school early, to start families early and to
      smoke during pregnancy, thus continuing the 'family circle' or 'cycle of
      deprivation'. Practical action is needed.

PMID- 8746300
TI  - Tobacco control: overview.
AB  - This chapter assesses the principal components of an effective tobacco control
      programme in relation to efficacy, reach (i.e. numbers of smokers influenced) and
      cost-effectiveness. National targets for the reduction of prevalence are most
      likely to be achieved through the use of high reach interventions such as fiscal
      policy and mass communications. Restrictions on smoking at work may contribute to
      declines in consumption, but advice from health professionals, though effective,
      has limited impact owing to low reach. Measures aimed primarily at youth can
      delay, but not prevent, recruitment to smoking. Media publicity not only reduces
      smoking, but also creates a climate of opinion in favour of effective measures
      such as fiscal policy. In the long run, health professionals can achieve more for
      their patients through the media than through personal advice.

PMID- 8746301
TI  - The ethics of tobacco advertising and advertising bans.
AB  - In this chapter, I will examine the main ethical parameters of the arguments
      pertaining to the alleged 'right' to advertise tobacco products and those
      maintaining that it should be banned. In particular, I will explore the ethics of
      the adoption of 'partial' bans on tobacco advertising, since there are now few
      countries which do not restrict tobacco advertising in some way.

PMID- 8746302
TI  - Price and consumption of tobacco.
AB  - Progressive increases in cigarette tax rates provide a powerful contribution to
      policy for reducing cigarette consumption and generate extra government revenue.
      The policy has been most effective in groups for whom health publicity effects
      have been least so, but special provision may be necessary to avoid hardship to
      poor families.

PMID- 8746303
TI  - Tobacco and the law: the state of the art.
AB  - Litigation has become a major weapon in the conflict between those who seek to
      control tobacco and the tobacco industry. Apart from the cases arising from the
      high proportion of fires caused by cigarettes (including, in the UK, the
      disastrous fire at the Bradford football stadium and the fire at Kings Cross
      railway station, both of which were caused by discarded cigarette butts), in the
      last few years there have been and are continuing major lawsuits against the
      tobacco manufacturers both in the USA and in the UK. In Australia, a Court has
      ruled that the tobacco industry's claims that passive smoke had not been proven
      to cause a variety of diseases were false and misleading. A Quebec judge ruled as
      unconstitutional a Canadian law which had banned tobacco advertising. A product
      liability suit was filed against cigarette manufacturers by airline flight
      attendants whose health, they alleged, was impaired by exposure to passive smoke.
      To date, attempts to win damages from the manufacturers for injuries caused by
      smoking have failed, but several group actions are pending in the courts in
      England and the USA. The cases to date demonstrate the range and importance of
      tobacco control issues now being considered by the Courts.

PMID- 8746304
TI  - Strategies for smoking cessation.
AB  - Smoking cessation strategies should be geared to the target group's level of
      motivation to quit, and degree of tobacco addiction. Motivational interventions
      (e.g. media campaigns) aim to encourage more people to try to stop smoking.
      Treatment interventions (e.g. nicotine replacement) aim to increase the chances
      of a quit attempt being successful. In populations which have already been
      saturated by motivational interventions, the overall effect of adding further
      motivational interventions may be rather small, and possibly non-existent in
      heavy smokers. As a population's smoking prevalence declines, so the balance of
      interventions should shift from motivational to treatment approaches. Nicotine
      replacement is an effective smoking cessation aid and should form the basis for
      treating moderate to heavy smokers. There may be a case for the development of
      more specialist clinics to treat motivated but addicted smokers and train health
      professionals how to apply effective smoking cessation methods as part of their
      routine work.

PMID- 8746305
TI  - Forty years on: a war to recognise and win. How the tobacco industry has survived
      the revelations on smoking and health.
AB  - Nothing has significantly checked the growth of the tobacco industry since the
      introduction of smoking to Europe, and the industry has easily survived the 40
      years since the first authoritative revelations about the health effects of
      smoking. Some explanations are offered and the tactics of the industry and the
      response of the UK Government are reviewed. The policies of British-American
      Tobacco and its subsidiaries, especially Brown and Williamson in the USA, are
      considered in detail, including the rejection of an early proposal for a
      pragmatic but honest deal. In particular, an internal document from 1970 is
      examined in which BAT purports to set policy for the whole industry. The document
      is revealed as showing far-sighted but cynical calculation, for instance, in
      limiting concessions to those countries where public and government awareness
      requires them. Examples of BAT activities are quoted to illustrate key points.

PMID- 8746306
TI  - Tobacco industry tactics.
AB  - The tobacco industry's strong-arm tactics have been used consistently over many
      years. These tactics include: using the industry's size, wealth, and legal
      resources to intimidate individuals and local governmental bodies; setting up
      'front groups' to make it appear that it has more allies than it really does;
      spending large sums of money to frame the public debate about smoking regulations
      around 'rights and liberty' rather than health and portraying its tobacco company
      adversaries as extremists; 'investing' thousands of dollars in campaign
      contributions to politicians; and using financial resources to influence science.
      These tactics are designed to produce delay, giving the nicotine cartel more time
      to collect even more profits at the direct expense of millions of lives around
      the world.

PMID- 8746307
TI  - Product modification.
AB  - For more than 20 years there has been a coherent programme of product
      modification in the UK, involving the introduction of low tar brands of
      cigarettes and the gradual reduction in average tar yields over the whole range
      of manufactured cigarettes. The sales-weighted average tar yield has declined
      from 20.8 mg/cigarette in 1972 to 11.0 mg/cigarette in 1993. To some extent
      potential benefits to established smokers have been offset by their tendency to
      'compensate' for reduced nicotine yields. Investigating such aspects has formed
      one part of a wide-ranging research programme to monitor effects of modified
      products on health. Collectively the studies show benefits in terms of smoke
      intake and health outcome related to reduced tar cigarettes, but the success
      achieved in reducing average tar yields and narrowing the range has limited
      opportunities to detect differential effects.

PMID- 8746308
TI  - Tobacco and the developing world.
AB  - Tobacco consumption is increasing in developing countries, which will bear the
      brunt of the tobacco epidemic in the 21st century. If current smoking patterns
      continue, 7 of the world's 10 million annual deaths from tobacco in 2025 will
      occur in developing countries. Compared with developed countries, more men and
      fewer women currently smoke in developing countries, but smoking among girls and
      women is increasing. While indigenous tobacco production and consumption remain a
      major problem, of particular concern is the penetration by the transnational
      tobacco companies, bringing with them denial of the health evidence,
      sophisticated advertising and promotion, threats of trade sanctions based on
      tobacco trade, and opposition to tobacco control measures, in particular
      promotional bans and tobacco tax policy. Developing countries must urgently
      devise and implement national tobacco control policies, but many governments have
      little experience in the new noncommunicable disease epidemic or in countering
      the transnational tobacco companies.

PMID- 8746309
TI  - External fixation of the wrist.
AB  - External fixation for fractures of the distal radius has been used for almost 80
      years. The main objective is to gain reduction and maintain the reduction
      throughout the treatment period. Several fixator concepts are available and
      selection is based on the complexity of the case to be treated as well as the
      surgeon's experience. Periarticular application of the fixator with immediate use
      of the wrist joint is recommended whenever possible. In intra-articular fractures
      transarticular application is advisable. External fixation in complex fractures
      has to be supplemented by bone grafting, fixation wires and stabilization of the
      radioulnar joint. Associated injuries in distal radius fractures need to be
      identified and treated. The possible complications of external fixation are
      discussed and means to prevent them are referred to. External fixation of the
      distal radius has found its place as an established method in treating certain
      types of this common fracture.

PMID- 8746310
TI  - Functional outcome after incomplete spinal cord injuries due to blunt injury.
AB  - During a 3-year period, 19 patients with incomplete spinal cord injuries caused
      by blunt trauma were admitted to a single rural referral centre. The mean age was
      50 years. Injury mechanisms included falls in eight, road traffic accidents in
      five, diving mishaps in two, and miscellaneous in four. The level of spinal cord
      injury was cervical in 11, thoracic in five, and thoracolumbar in three. Initial
      management included a standard high-dose methylprednisolone protocol for 24 h
      after injury in eight patients treated since May, 1990. Neurosurgical procedures
      were performed in 11 patients. There were three deaths, all in patients over 75
      years of age with pulmonary complications. Of 16 survivors, 10 demonstrated
      significant functional neurological improvement by the time of hospital
      discharge, and 11 by late follow up. Complete recovery occurred in five of the
      survivors. Complications occurred in 11 patients, including pulmonary (nine),
      infectious (six), and gastrointestinal (three), but could not be associated
      specifically with the high-dose steroid protocol. In conclusion, incomplete
      spinal cord injuries after blunt injury were relatively uncommon in this setting.
      No significant increase in complications was observed after institution of the
      high-dose methylprednisolone protocol in May, 1990. However, pulmonary,
      gastrointestinal, and infectious complications were common. Of the 16 survivors,
      11 demonstrated significant functional improvement. Mortality appeared to be
      related to advanced age and to pulmonary complications.

PMID- 8746311
TI  - Vehicle entrapment rescue and pre-hospital trauma care.
AB  - From 1 April 1991 to 31 March 1993 the Royal London Hospital Helicopter Emergency
      Medical Service (HEMS) attended 737 road traffic accidents, 90 (12 per cent) of
      which involved entrapments. Nine casualties (10 per cent) died, of which five
      died at the scene. Thirty-two patients with a median ISS 17 (range 1-59) were
      transported by helicopter to the Royal London Hospital. Of these, four
      subsequently died in hospital. The median ISS of the non-survivors was 44 (range
      24-59). The remaining 53 patients were transported to the nearest hospital. In 45
      cases (50 per cent) patient extrication took longer than 30 min. The methods and
      standards for the release of trapped road traffic accident victims were reviewed
      to allow physicians a working understanding of Fire Service techniques.
      Entrapment rescue should create rapid access to the accident victim, allowing
      stabilization and release with minimum delay. Immediate and uncontrolled release
      of trapped victims is only indicated if there is immediate danger to life from
      the surroundings. We recommend a rigorous target of less than 30 min for the
      release of the casualty. To achieve this will require systematic extrication
      training for Fire Service crews and medical teams who are involved in immediate
      care.

PMID- 8746312
TI  - The Mennen plate in periprosthetic hip fractures.
AB  - We would like to report five patients with periprosthetic hip fractures, treated
      with a Mennen plate, as we felt there were contraindications to revision surgery
      in these patients. Their average age was 79.1 years. All patients were
      uncomfortable in Thomas splint traction and more comfortable after surgery; they
      required an average of 2 units of blood to be transfused; they were partially
      weight-bearing with a caliper in an average of 9 weeks, home in an average of 10
      weeks, and the average time to clinical or radiological union was 4.8 months. We
      considered a reasonable level of mobility was regained after surgery and would
      recommend Mennen plate fixation for periprosthetic fractures in those patients
      perhaps too frail for revision.

PMID- 8746313
TI  - Circular frames in the management of infected tibial non-union: a modification of
      the Papineau technique.
AB  - We have treated five patients with an infected non-union of the tibia by a
      modification of the Papineau technique, consisting of a wound microenvironment
      chamber and bone stabilization with a circular frame. In all cases bone union and
      elimination of infection was achieved.

PMID- 8746314
TI  - Assessing outcome following calcaneal fracture: a rational scoring system.
AB  - Six existing clinical scoring systems for assessing outcome after calcaneal
      fracture are reviewed. All were applied to a diverse group of 75 patients who had
      sustained this injury. Stepwise multiple regression analysis was used to identify
      the most relevant variables within these systems. Based on this, a simplified and
      rational outcome scoring system was devised. This system was then tested on a
      further group of 41 patients and shown to comply well with the characteristics
      required of an objective outcome score.

PMID- 8746315
TI  - Early experiences with the AO calcaneal fracture plate.
AB  - We describe our early experiences using the new AO plate for open reduction and
      internal fixation of displaced intra-articular fractures of the calcaneum. An
      overview of our operative technique based on 22 cases is given. The relative
      merits of the new plate are discussed and we conclude that the plate is a useful
      device for dealing with this complex injury.

PMID- 8746316
TI  - Knee arthroscopy under local anaesthesia: results and evaluation of patients'
      satisfaction.
AB  - A study of 55 consecutive knee arthroscopies under local anaesthesia was
      undertaken, in order to evaluate the effectiveness, patient satisfaction and
      acceptability of the procedure. Knee arthroscopy was performed without a thigh
      tourniquet under low volume (20 ml) local anaesthesia using half the recommended
      safe dose of anaesthetic agents, as a single intra-articular injection together
      with skin infiltration of the arthroscopic portals. The diagnostic accuracy and
      effectiveness of the procedure was similar to that of surgery under general
      anaesthesia. Sixty-two lesions were diagnosed and 48 surgical procedures were
      successfully carried out in 53 patients. All but one of the questioned patients
      (97 per cent) were satisfied with the procedure which caused little or no
      discomfort in 94 per cent of cases. It is concluded that knee arthroscopy under
      local anaesthesia may be considered as a reliable, well tolerated and safe
      alternative to conventional procedures.

PMID- 8746317
TI  - Sexual dysfunction in women following pelvic fractures with sacro-iliac
      disruption.
AB  - We report the results of a postal questionnaire sent to a group of women who had
      sustained major pelvic fractures and sacroiliac disruption. The findings suggest
      that a large proportion of women suffer sexual dysfunction after such injuries.
      This is an important and previously neglected sequel of pelvic injuries.

PMID- 8746318
TI  - Treatment of unstable distal clavicular fractures with and without lesions of the
      acromioclavicular joint.
AB  - A series of 39 unstable fractures of the distal one-third of the clavicle is
      presented. As results after non-operative treatment of these fractures are poor,
      surgical therapy is indicated. In fractures with a small peripheral fragment or
      with an associated separation of the acromioclavicular joint, PDS-banding is a
      valuable technique for stabilization. According to the classification of Neer and
      Jager/Breitner, a clear therapeutic strategy for lateral clavicular fractures can
      be defined. Unstable clavicular fractures with associated acromioclavicular
      ligament disruption should however be considered as a separate subtype in the
      existing classifications.

PMID- 8746319
TI  - Percutaneous pinning in undisplaced subcapital femoral neck fractures.
AB  - Three hundred and five undisplaced subcapital femoral neck fractures managed by
      pinning in situ with Knowles' pins were evaluated to elucidate the role and
      effect of such treatment. The protocol of management and follow up, and
      evaluation, both radiographically and functionally, were set up prospectively.
      The duration from injury to management was 3.5 (1-14) days, the operation time
      was 22 (9-48) min and most of the patients were discharged without
      hospitalization. The follow-up period was 75 (28-136) months. The final results
      showed 282 (92.5 per cent) fractures united without complications (mean union
      time: 20 weeks), 14 (4.6 per cent) limbs with non-union, and 9 (2.9 per cent) had
      implant problems. Twenty-two (7.2 per cent) developed avascular necrosis after
      union. Percutaneous pinning of undisplaced subcapital femoral neck fractures as
      day cases is a simple, safe, effective and economic method.

PMID- 8746320
TI  - Dynamic external fixation versus non-operative treatment of severe distal radial
      fractures.
AB  - Severe distal radius fractures often lead to impairment of wrist function,
      particularly in younger patients. This paper reports 55 consecutive patients
      younger than 65 years with displaced intra-articular fractures of the distal
      radius. Twenty-nine were treated with dynamic external fixation, and 26 with
      closed reduction and plaster cast immobilization. At least 1 year after the
      injury the anatomical and functional results were assessed using the scoring
      system of Lidstrom. In a retrospective analysis, both the anatomical and
      functional end score were significantly better in the dynamic external fixation
      group than in the group treated non-operatively (0.02 P < 0.05 using chi 2
      analysis with Yates' correction). We conclude that dynamic external fixation is a
      good alternative for non-operative treatment in younger patients with severe
      distal radial fractures. Prospective evaluation of this subject is necessary.

PMID- 8746321
TI  - Accidental shotgun injuries sustained in game-shooting.

PMID- 8746322
TI  - Combination subcapital and intertrochanteric fractures of the femoral neck.

PMID- 8746323
TI  - Penetrating head injuries: a trap for the unwary.

PMID- 8746324
TI  - Trash foot following injury: an unusual presentation of abdominal aortic
      aneurysm.

PMID- 8746325
TI  - Natural tolerance in a simple immune network.
AB  - The following basic question is studied here: In the relatively stable molecular
      environment of a vertebrate body, can a dynamic idiotypic immune network develop
      a natural tolerance to endogenous components? The approach is based on stability
      analyses and computer simulation using a model that takes into account the
      dynamics of two agents of the immune system, namely B-lymphocytes and antibodies.
      The study investigates the behavior of simple immune networks in interaction with
      an antigen whose concentration is held constant as a function of the symmetry
      properties of the connectivity matrix of the network. Current idiotypic network
      models typically become unstable in the presence of this type of antigen. It is
      shown that idiotypic networks of a particular connectivity show tolerance towards
      auto-antigen without the need for ad hoc mechanisms that prevent an immune
      response. These tolerant network structures are characterized by aperiodic
      behavior in the absence of auto-antigen. When coupled to an auto-antigen, the
      chaotic attractor degenerates into one of several periodic ones, and at least one
      of them is stable. The connectivity structure needed for this behavior allows the
      system to adopt particular dynamic concentration patterns which do not lead to an
      unbounded immune response. Possible implications for the understanding of
      autoimmune disease and its treatment are discussed.

PMID- 8746326
TI  - Wavelet analysis of olfactory nerve response to stimulus.
AB  - Multiunit electrophysiological activity recorded by gross electrodes from the
      olfactory nerve was analyzed by wavelet decomposition, a relatively new method of
      signal processing. The analysis was run on data from the unstimulated olfactory
      system as well as on data evoked in response to six different odorant stimuli.
      Like Fourier analysis, wavelet analysis provides a spectral decomposition of the
      signal. Unlike Fourier, wavelet analysis also locates the dominant spectral
      features in time. The output of a wavelet analysis can be further processed to
      enhance selected features. The increased amplitude of the nerve response evoked
      by stimulation was the most obvious feature, but efforts to learn from it were
      unproductive. The temporal pattern of receptor cell activity was much more
      yielding. The analysis resolved the nerve activity into three classes of events
      based on duration. On wavelet maps these classes of events separate out into
      three shifting and overlapping but distinct bands, one of which was interpreted
      as being associated with individual receptor cell firings and the other two as
      short and somewhat longer duration bursts of activity that was attributed to the
      synchronized firing of a group of receptor cells. This interpretation is
      supported by experiments in which waveforms simulating action potentials and
      bursts of action potentials are added to recorded data. Stimulation of the
      olfactory system with odorant molecules evokes a significant increase in the
      number of short duration bursts, and an amplitude increase that can be related to
      the number of receptor cells responding. Changes in the patterns of wavelet
      events can be associated with synchrony of cell firing, reset times for bursts of
      firing, and possibly other physiological dynamics. A number of differences in
      activity patterns with different odorants were observed, but without sufficient
      repeatability to allow reliable discrimination among them. While this study is
      clearly preliminary in that regard, it shows the potential of the wavelet method
      for contributing to the understanding of olfaction.

PMID- 8746327
TI  - A genetical theory of species selection.
AB  - Species selection, differential rates of speciation or extinction resulting from
      species level characters, is often invoked as the main mechanism of
      macroevolution that is not simply an extension of microevolutionary processes. So
      long as we are careful in defining "species", the logic of species selection is
      sound. This does not mean, however, that this process can influence evolutionary
      dynamics under realistic conditions. The principal challenge to the efficacy of
      species selection as an evolutionary mechanism is the idea that selection between
      individuals within species will be so much more efficient as to swamp out any
      effects of selection between species. To assess this, a genetic model is
      constructed that includes simultaneous selection within and between species, and
      this is used to ask: under what conditions could species selection influence
      evolutionary dynamics, even in the face of opposing selection between
      individuals? The model shows that the efficacy of species selection is strongly
      determined by the time between speciation events (measured in individual
      generations), the mutation rate of the character under consideration, and the
      initial size of a newly formed reproductively isolated population. Data indicate
      that a few studied lineages have shown sufficiently high speciation rates to make
      species selection an important mechanism in the evolution of characters with
      mutation rates on the order of 10(-6) per generation. Quantitative characters,
      such as body size, generally change too readily for species selection to be
      relevant to their evolution. Complex characters, however, may be good candidates
      to be influenced by species selection. The interaction of selection within and
      between species can be subtle, with individual selection looking, from the
      standpoint of a species, very much like development of an individual.
      Furthermore, selection between individuals may be the main process assembling
      complex adaptations, while species selection allows them to persist over long
      periods of time.

PMID- 8746328
TI  - Modelling the optimal simulation path in the peptide chain folding--studies based
      on geometry of alanine heptapeptide.
AB  - The theoretical background of a simple model of polypeptide chain structure using
      two parameters: R (A)--the radius of curvature for each pentapeptide chain
      fragment in the protein, and V (deg)--the dihedral angle between two consecutive
      peptide bond planes, is presented. The mathematical relationship between these
      two geometrical parameters leads to the optimal searching path for low-energy
      peptide conformations. This R versus V relation, corresponding to low-energy
      structures in Ramachandran plot, appeared to fit the square function well. Here,
      the minimum of this function is taken as the optimal starting point for the
      minimization of all second-order conformations in the peptide chain. The
      extension, including all structures that satisfy the square function between V
      and R, showed the Phi, Psi angles that are optimal in searching for the path to
      low-energy structures. The path is an ellipse connecting the alpha R-, beta- and
      alpha L-structures, indicating the possible transitions from one to the next.

PMID- 8746329
TI  - Nickel-containing alloys and platings and their ability to cause dermatitis.
AB  - A broad range of nickel-containing alloys and coatings used in jewellery, watches
      and clothes, were patch tested in 100 nickel-sensitive subjects and in 20 nickel
      negative controls. Three non-plated stainless-steel alloys tested caused no patch
      test reaction. Nickel interliners under gold, silver or chromium plating, as well
      as nickel-silver and some white-gold alloys, caused positive patch-test
      reactions. Ear ornaments, wristwatches and buttons were the objects most
      frequently causing dermatitis. Half the nickel-sensitive participants suspected
      that they had been sensitized before the age of 20. The results of the study have
      been used as the basis for developing clinically relevant analytical methods for
      nickel release. The methods are proposed as European Standards and will be used
      in the Nickel Directive, an EC regulation aiming at the prevention of nickel
      allergy.

PMID- 8746330
TI  - Chromium- and nickel-induced cytotoxicity in normal and transformed human
      keratinocytes: an investigation of pharmacological approaches to the prevention
      of Cr(VI)-induced cytotoxicity.
AB  - Chromium and nickel compounds cause irritancy but can also induce allergic
      contact dermatitis. The aims of this study were to characterize the direct
      cytotoxic effects of Cr(VI), Cr(III) and Ni(II) salts on keratinocytes, and to
      investigate pharmacological strategies to protect cells against Cr(VI)-induced
      cytotoxicity. Normal human keratinocytes and the HaCaT keratinocyte cell line
      were used. Cell viability was assessed by neutral red dye uptake, the 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) eluted stain assay
      and measurement of lactate dehydrogenase (LDH) activity in the medium. The assays
      varied slightly in their sensitivities (neutral red > MTT > LDH) although all
      three gave similar results. In both cell types, the relative order of
      cytotoxicity of the salts was Cr(VI) >> Ni(II) > Cr(III). There were no major
      differences between chromium salts of a common valency. Normal human
      keratinocytes showed a much greater variability in their response to Cr(VI) and
      Ni(II) salts than HaCaT cells and were generally more resistant to Cr(VI)- and
      Ni(II)-induced cytotoxicity. Several drugs were screened for their potential to
      protect both cell types against the cytotoxic effects of Cr(VI), specifically the
      reducing agents ascorbic acid, cysteine and glutathione, and the Cr(VI) cellular
      uptake inhibitors 4,4'-diisothiocyanato-2,2'-stilbenedisulphonic acid (DIDS) and
      4-acetamido-4'-isothiocyanato-2,2'-stilbenedisulphonic acid (SITS). All five
      drugs provided concentration-dependent protection against Cr(VI)-induced
      cytotoxicity but only ascorbic acid offered complete protection. Several of these
      pharmacological approaches to the prevention of Cr(VI) cytotoxicity confirm
      previous clinical studies on the inactivation of Cr(VI), while the clinical
      potential of others has yet to be investigated.

PMID- 8746331
TI  - Studies on the reproducibility of allergic contact dermatitis.
AB  - Diagnosis of allergic contact dermatitis depends upon the use of epicutaneous
      patch tests with suspected antigens. It has been claimed that the method is
      unreliable because of variability. Therefore, we have tested this by comparing
      responses to various forms of replicate, standardized challenge in nickel
      sensitive subjects. Nickel-containing coins applied at 2-4 different sites on the
      back elicited similar responses in up to 95% of tests. Serial dilutions of nickel
      sulphate (NiSO4) applied, in duplicate, gave highly reproducible responses on the
      back. However, the forearm skin was clearly less responsive. Examination of the
      effect of the quantity of nickel-containing vehicle showed that, above a certain
      minimal level, this had no effect on the reproducibility of the responses. In
      conclusion, the immune system can give highly reproducible responses when
      presented with standard eliciting stimuli.

PMID- 8746332
TI  - Effect of topically applied lipids on surfactant-irritated skin.
AB  - Moisturizers are used daily by many people to alleviate symptoms of dry skin. All
      of them contain lipids. It has been suggested that topically applied lipids may
      interfere with the structure and function of the permeability barrier. The
      influence of a single application of nine different lipids on normal skin and
      skin irritated by sodium lauryl sulphate (SLS) was studied in 21 healthy
      subjects. Parameters assessed were visible signs of irritation, and objectively
      measured cutaneous blood flow and transepidermal water loss (TEWL). The
      substances tested were hydrocortisone, petrolatum, fish oil, borage oil,
      sunflower seed oil, canola oil, shea butter, and fractions of unsaponifiable
      lipids from canola oil and shea butter. Water was included as a control. On
      normal skin, no significant differences in the effects of the test substances
      were found, whereas significant differences were observed when they were applied
      to SLS-irritated skin. The visible signs of SLS-induced irritation were
      significantly less pronounced after treatment with the sterol-enriched fraction
      from canola oil than after treatment with water. This fraction, and
      hydrocortisone, reduced cutaneous blood flow. Furthermore, application of
      hydrocortisone, canola oil, and its sterol-enriched fraction, resulted in
      significantly lower TEWL than with water. The other lipids had no effect on the
      degree of irritation. In conclusion, lipids commonly used in moisturizers may
      reduce skin reactions to irritants. Previous studies have shown that, in barrier
      perturbed skin, the synthesis of sterols is increased. The observed effects of
      canola oil and its fraction of unsaponifiable lipids on SLS-induced irritation
      suggest the possibility that they assisted the skin in supplying the damaged
      barrier with adequate lipids.

PMID- 8746334
TI  - Percutaneous absorption of hydrocortisone and testosterone on the vulva and
      forearm: effect of the menopause and site.
AB  - The percutaneous absorption of hydrocortisone and testosterone was studied
      following their application to the vulvar and ventral forearm regions of pre- and
      post-menopausal women. Percutaneous absorption of hydrocortisone was
      significantly greater in vulvar skin than forearm skin in both pre- and post
      menopausal women (P < 0.05, respectively), whereas the percutaneous absorption of
      testosterone was significantly increased (P < 0.01) on the vulva compared with
      the arm only in post-menopausal women. The effect of age on the percutaneous
      absorption of hydrocortisone and testosterone was evaluated by using the
      menopause as a biological chronometric end point. It is a common misconception
      that older skin has a diminished barrier capacity, and that percutaneous
      absorption is therefore greater. Our studies showed that absorption of
      hydrocortisone vulval skin of pre-menopausal women was significantly greater (P <
      0.01) than in post-menopausal women. The ventral forearm skin of pre-menopausal
      women tended to show increased absorption compared with post-menopausal women,
      but statistical significance was not reached. No significant differences (P >
      0.05) in the percutaneous absorption of testosterone in vulval or forearm skin
      were observed between the two age groups.

PMID- 8746333
TI  - Correlation of impedance response patterns to histological findings in irritant
      skin reactions induced by various surfactants.
AB  - We have explored the use of measurements of electrical impedance to discriminate
      between the effects of different irritant substances upon the skin, and have
      studied the relationships between impedance and histopathological change. Three
      compounds with different chemical profiles were tested on volunteers: sodium
      lauryl sulphate, benzalkonium chloride and nonanoic acid. The concentrations
      selected were such that each irritant produced responses of a similar order, as
      judged by visual scores. The magnitude and phase of electrical impedance were
      measured and, for comparison, also the transepidermal water loss. Four physically
      distinct aspects (indices) were devised from the impedance data, and the values
      obtained were statistically analysed. The three irritants produced different
      effects, giving distinctive impedance patterns. These were also found to be
      reflected by three different types of histopathological skin response. Our
      results suggest that the indices can be used to classify irritant contact
      reactions, which it is difficult or impossible to achieve by other non-invasive
      techniques.

PMID- 8746335
TI  - Effects of dithranol on neutrophil superoxide generation in patients with
      psoriasis.
AB  - The effect of dithranol on superoxide generation in vivo has not been studied
      previously. Neutrophils produce large amounts of superoxide following stimulation
      by phorbol 12-myristate-13-acetate (PMA). We studied the effect of dithranol on
      PMA-activated superoxide generation by isolated neutrophils from normal subjects,
      and measured whole blood luminescence in response to PMA, using samples from 13
      psoriatic patients before and during dithranol treatment. Oxidized dithranol had
      no effect on the PMA-stimulated superoxide generation in neutrophils, but there
      was a modest dose-related increase in superoxide generation by neutrophils
      exposed to dithranol before activation. Similar results were found with
      neutrophils obtained from the 13 psoriasis patients. Three of these patients
      suffered a dithranol burn and developed a neutrophilia, with a marked increase in
      stimulated superoxide generating ability. Our findings suggest that dithranol
      treatment of a psoriasis plaque is associated with a decrease in oxygen radical
      generating capacity in vivo. However, where inflammation of perilesional and
      uninvolved skin occurs, neutrophils appear to become semi-activated or primed.

PMID- 8746336
TI  - Efficacy and safety of topical calcitriol (1,25-dihydroxyvitamin d3) for the
      treatment of psoriasis.
AB  - Plaque-type psoriasis has been successfully treated with topical calcitriol, but
      there has been no long-term follow-up study of the safety and efficacy of this
      calciotropic hormone. In a single-centre study, patients with plaque or
      erythrodermic psoriasis were enrolled in a double-blind, right/left comparison,
      placebo-controlled study, and received 1.5 micrograms of calcitriol (15
      micrograms/g of Vaseline) per day, or a placebo consisting of Vaseline alone. A
      subset of these patients (n = 22), with at least 25% involvement, applied 0.1 g
      of calcitriol ointment/50 cm2 on an area of from 2,500 to 5,000 cm2. Of the 84
      patients enrolled in the double-blind control study, 96.5% responded to topical
      calcitriol therapy, compared with 15.5% whose lesions improved with Vaseline
      alone, after 2.4 months. After completion of the double-blind study, 22 patients
      applied calcitriol ointment (15 micrograms/g Vaseline) to all of their lesions
      (up to 10 g of calcitriol ointment; 150 micrograms calcitriol lesions showed
      either excellent or moderate clearing in 90.9% of all cases. The remaining 9.1%
      of cases showed slight improvement of their lesions. No abnormalities in calcium
      metabolism were noted in any of the patients using topical calcitriol. None of
      the patients experienced any local cutaneous side-effects, including six patients
      who applied calcitriol ointment to the face. Topical calcitriol is safe and
      effective for the treatment of psoriasis.

PMID- 8746337
TI  - Keratin expression in pilosebaceous epithelia in truncal skin of acne patients.
AB  - This study compared the pattern of keratin expression in pilosebaceous follicles
      in uninvolved trunk skin of acne patients, comedones, and normal control skin by
      immunohistochemistry, using both immunofluorescent (IF) and immunoperoxidase (IP)
      techniques. The shape, size and gross morphology of truncal follicles varied
      greatly. There was no difference in keratin expression between normal skin and
      uninvolved skin of patients with acne. The upper part of the pilosebaceous duct
      expressed keratins K1, K5, K10 and K14, whereas the lower duct expressed keratins
      K5, K6, K14, K16, K17 and K19. The sebaceous gland showed considerable
      heterogeneity in keratin expression, with some lobules expressing keratins K1,
      K5, K7, K10, K14 and K17. The comedone wall showed a pattern of keratin
      expression similar to that of the upper follicle, except that there was, in
      addition, expression of keratins K6 and K16 suprabasally, and panepithelial
      expression of K17 in the comedone wall. IF techniques were found to be less
      sensitive than the IP method in the detection of individual keratins, but the use
      of multiple antibodies and many different transverse and longitudinal sections of
      follicles permitted full conclusions to be made. The increased expression of
      keratins K6, K16 and K17 in the comedone wall is likely to represent a secondary
      effect of increased cell turnover due to the primary underlying mechanism of
      comedogenesis, which is as yet unknown.

PMID- 8746338
TI  - Mucocutaneous manifestations in 22 consecutive cases of primary HIV-1 infection.
AB  - Twenty-two consecutive patients presenting with symptomatic human
      immunodeficiency virus 1 (HIV-1) seroconversion were studied. Most of the
      patients had a glandular fever-like illness. All patients had fever and
      pharyngitis, and eight of them also suffered from ulcers of the oral, genital or
      anal mucosa. Uniform skin eruptions were observed in 17 of the 22 patients. The
      exanthem consisted of varying numbers of macular or maculopapular lesions that
      were oval or rounded in shape, ranging from a few millimetres to 1 cm in
      diameter. The lesions were distributed on the upper thorax in all cases, and were
      particularly profuse in the collar region. The face, forehead and scalp were
      involved in most cases, but the eruption was sparse or absent at the periphery of
      the extremities. In the majority of patients, the exanthem appeared after 2 or 3
      days of fever. The exanthem developed during the first day, persisted for 5-8
      days, and then cleared concurrently with the general recovery of the patients.
      Histopathological studies of skin punch biopsy specimens from four patients
      showed a sparse lymphocytic cell infiltrate distributed around vessels of the
      dermal superficial plexus. The infiltrates predominantly consisted of equally
      represented T-helper/inducer and T-suppressor/cytotoxic cells. A vacuolar
      aberration of basal layer cells was found in two of the four cases studied
      histologically. The microscopic findings correspond to the histopathological
      patterns seen in toxicodermia and in the interface dermatitis of morbilliform
      viral exanthems. The exanthem is a frequent and characteristic sign of primary
      HIV infection, which is further indicated if mucosal ulcers are present.

PMID- 8746339
TI  - A study of the kinetics and pattern of E-selectin, VCAM-1 and ICAM-1 expression
      in chronic actinic dermatitis.
AB  - It has been postulated that chronic actinic dermatitis (CAD), an eczematous
      photodermatosis, is a type IV hypersensitivity reaction. Expression of adhesion
      molecules on dermal blood vessels is critical to the recruitment of inflammatory
      cells into the skin; the pattern and kinetics of upregulation of these molecules
      in the skin differ following ultraviolet irradiation and delayed hypersensitivity
      reactions. We therefore investigated the kinetics of expression of endothelial
      leucocyte adhesion molecules (E-selectin) vascular-cell adhesion molecules 1
      (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) in CAD lesions induced by
      suberythemal solar-stimulated radiation, by immunohistochemical staining of
      biopsies taken at 1-168 h after irradiation. In control, unirradiated skin from
      CAD patients, baseline vessel-associated and interstitial ICAM-1, and vessel
      associated VCAM-1 were noted; focal keratinocyte ICAM-1 expression was observed
      in two of the five patients. Endothelial E-selectin, and vessel-associated and
      interstitial VCAM-1 expression, were upregulated in induced lesions by 1-5 h in
      all patients, and remained elevated at 120-168 h. Vessel associated, dermal
      interstitial, and keratinocyte ICAM-1 expression was upregulated in all patients
      at 24 h, and remained increased at 120-168 h. These findings differ from those
      observed following ultraviolet irradiation of normal skin, and resemble those
      seen in normal skin during a delayed-type hypersensitivity reaction, supporting
      the hypothesis that CAD involves a type IV response to an as yet unidentified
      photo-induced antigen.

PMID- 8746340
TI  - Immunohistochemical detection of CDK4 and p16INK4 proteins in cutaneous malignant
      melanoma.
AB  - p16INK4 gene, which encodes a specific inhibitor of cyclin-dependent kinase 4
      (CDK4), has been recently reported as an important tumour suppressor gene. It is
      mapped to chromosome 9p21, which is frequently deleted or mutated in many tumour
      cell lines including malignant melanoma. Since the CDK4/cyclin D complex propels
      a cell to go through the G1 check point of the cell cycle, a critical phase of
      cell division, alteration of the p16INK4 gene could lead a cell to uncontrolled
      proliferation and malignant transformation. To clarify any role for p16INK4 and
      CDK4 proteins in the development of human malignant melanoma, we have examined,
      immunohistochemically, the expression of these two proteins in melanocytic
      neoplasms including 19 primary lesions of non-familial melanoma. Intense nuclear
      and/or cytoplasmic expression of the CDK4 protein was observed in 11 of 19 cases
      (58%) of melanoma. In contrast, virtually no nuclear or cytoplasmic staining for
      CDK4 protein was detected in 28 benign melanocytic naevi, including six Spitz
      naevi. Expression of p16INK4 protein was observed in three of 19 melanomas (16%)
      and in 17 of 28 benign naevi (61%). Inverse expression of CDK4 and p16INK4, at
      individual cell level, was detected in one case of melanoma. The present study
      suggests that CDK4 overexpression is characteristic for malignant melanoma, and
      probably reflects its autonomous accelerated cell proliferation. The expression
      rate of p16INK4 protein in malignant melanoma was lower than that in benign
      naevi, although the significance of p16INK4 deletion in melanoma development has
      not been definitely confirmed.

PMID- 8746341
TI  - Low incidence of Epstein-Barr virus presence in primary cutaneous T-cell
      lymphoproliferations.
AB  - Multiple biopsies taken from 76 European human immunodeficiency virus (HIV)
      negative patients with primary cutaneous T-cell lymphoproliferations, including
      mycosis fungoides (MF), pleomorphic T-cell lymphoma (PMTCL), anaplastic large
      cell lymphoma (ALCL) and lymphomatoid papulosis (LyP) were investigated for the
      presence of Epstein-Barr virus (EBV) through a combined approach. Polymerase
      chain reaction (PCR) was employed for EBV-DNA detection, in situ hybridization
      (ISH) for cellular localization of EBV-encoded nuclear RNAs (EBER1 and EBER2) and
      immediate early Bam H-fragment; lower frame (BHLF) RNA, and immunohistology (IH)
      for the identification of EBV-encoded latent membrane protein 1 (LMP1) and of
      nuclear antigen (EBNA) 2 expression. EBV-DNA was detectable by PCR in 15 of 76
      cases (19.7%). EBER-ISH combined with IH identified a variable, usually very low,
      number of infected neoplastic cells in only seven of the 15 EBV-DNA-harbouring
      cases. This discrepancy between the results obtained with PCR and ISH is
      apparently caused by the low number of the infected cells per tissue section. The
      PMTCL entity produced the greatest number of positive cases, whilst ALCL and LyP
      cases were almost constantly devoid of the virus. BHLF transcripts were not
      detectable in any case, nor did any of the EBER-positive cells show an LMP1 or
      EBNA2 expression. These data show that primary cutaneous T-cell
      lymphoproliferations display an infrequent association with a latent EBV
      infection and that the pathogenic role of the virus in the positive cases remains
      obscure as the virus frequently infects only a minority of the atypical cells.

PMID- 8746342
TI  - No detection of HTLV-I proviral DNA in lesional skin biopsies from Swiss and
      German patients with cutaneous T-cell lymphoma.
AB  - The search for an infective agent linked to cutaneous T-cell lymphoma (CTCL) has
      also included the human T-cell lymphotropic virus type I (HTLV-I). Using
      sensitive techniques such as Southern blotting under low stringency conditions of
      hybridization and polymerase chain reaction (PCR) with primer sets designed to
      match pol, env and pX sequences of HTLV-I, we have screened lesional skin
      biopsies of 50 Swiss and German patients suffering from CTCL. No evidence of
      proviral integration of HTLV-I could be demonstrated in any of our patients. Our
      results, as well as a review of the literature, indicate that at least for
      European patients, HTLV-I does not seem to play a role in the aetiology of CTCL.

PMID- 8746343
TI  - Lymphoproliferative responses to Borrelia burgdorferi in circumscribed
      scleroderma.
AB  - Humoral immune responses to Borrelia burgdorferi (Bb) have been reported to occur
      in certain patients with circumscribed scleroderma (CS) (morphoea). Together with
      the isolation of spirochaetes from CS skin biopsies, this finding was taken to
      suggest Bb as the aetiological agent of CS. Since there is cellular
      immunoreactivity to Bb in patients with chronic Lyme borreliosis (LB), Bb
      specific lymphocytic responses were tested in patients with CS. For this purpose,
      peripheral blood mononuclear cells from CS patients and, as controls, from
      patients with various manifestations of LB, and from healthy volunteers without
      any evidence of Bb infection, were exposed to Bb organisms for 5 days and then
      assayed for DNA synthesis. Stimulation indices (SI) > 10 were scored positive. By
      performing lymphocyte proliferation tests we found: (i) that not only patients
      with various manifestations of LB but also a considerable percentage of
      seropositive (five of 13 = 38%) and seronegative (six of 26 = 23%) CS patients
      exhibit an elevated Bb-induced lymphocyte proliferation; (ii) that the magnitude
      of the cellular response seen in CS patients is comparable to that encountered in
      patients with established Bb manifestations; and (iii) that, within a given
      patient, antibiotic therapy can result in a significant reduction of this
      response. These results support a causative role of Bb in at least some CS
      patients. Bb-induced lymphocyte responses were also seen in both seropositive and
      seronegative erythema chronicum migrans patients. These findings show that the
      pattern of Bb-specific immune responses is more complex than previously thought,
      and underscore the importance of lymphocyte function assays in evaluating the
      diagnosis of potential Bb infection in seronegative patients.

PMID- 8746344
TI  - The clinical spectrum of naevus anaemicus and its association with port wine
      stains: report of 15 cases and a review of the literature.
AB  - Fifteen patients with naevus anaemicus (NA) are reported. Twelve (8%) of 146
      patients with a port wine stain (PWS) attending a laser clinic were noted to have
      this abnormality. In a control population of 298 new dermatology out-patient
      attenders, specifically examined for the presence of NA, three (1%) further cases
      were found. The clinical features of patients with NA are described and the
      literature reviewed. This is the largest group of patients with this disorder
      described in the English literature. The association of NA and PWS is confirmed.
      This study suggests that NA is more common than previously considered.

PMID- 8746345
TI  - Resistance to activated protein C: a common anticoagulant deficiency in patients
      with venous leg ulceration.
AB  - Patients with leg ulcers caused by venous insufficiency often show evidence of
      previous deep venous thrombosis. Resistance to activated protein C (APC
      resistance) is a newly identified, autosomal dominant inherited defect in the
      anticoagulant system which significantly predisposes affected individuals to
      develop venous thrombosis. To elucidate the significance of APC resistance in
      venous leg ulcer patients, APC resistance was determined in plasma samples
      obtained from 46 unselected, consecutive patients with venous leg ulcers,
      admitted to hospital during a 6-month period. Twelve of the 46 patients (26%: 95%
      confidence limits, 14-41%) had APC resistance. APC resistance is thus a common
      anticoagulant deficiency among patients with venous leg ulceration and should be
      considered a risk factor for the development of venous leg ulcer disease.

PMID- 8746346
TI  - The expression of the c-kit receptor by epidermal melanocytes may be reduced in
      vitiligo.
AB  - The proto-oncogene c-kit encodes the transmembrane tyrosine kinase receptor that
      has a role in the growth regulation of various cell types including melanocytes.
      In the present study we have examined the expression of the c-kit protein in the
      skin of seven patients with vitiligo. Melanocytes positive for c-kit protein were
      observed in the basal layer in non-lesional skin and the mean number of 25.8 +/-
      5.2 (per 200 basal cells) compared with that of 21.8 +/- 3.5 from six control
      subjects. In perilesional skin there was a reduction in the numbers of c-kit
      positive melanocytes (6.7 +/- 2.6) and this was especially noticeable in six of
      the seven patients. Such a reduction was less obvious following staining with MEL
      5 and in only two subjects were the numbers of melanocytes below the normal
      range. This suggests that the reduction in c-kit staining was the result of
      decreased expression of the protein rather than a loss of melanocytes. No
      melanocytes, positive for c-kit protein, or after staining with MEL-5, were
      identified in lesional skin although isolated tyrosinase-positive melanocytes
      were seen in one subject. There was no apparent change in the numbers of mast
      cells expressing c-kit protein and the intensity of staining in the dermis even
      in lesional skin was similar to that in the controls. These results demonstrate
      that c-kit protein is present on melanocytes in adult human skin and that in
      perilesional skin of some vitiligo patients there is a reduction in the numbers
      of melanocytes expressing this receptor. Whether this may contribute to the
      defective melanocyte growth and/or survival that occurs in vitiligo or whether it
      is a consequence of melanocyte damage remains to be seen.

PMID- 8746347
TI  - Lymphatic function in the yellow nail syndrome.
AB  - Peripheral oedema is commonly seen in the yellow nail syndrome (YNS). Contrast
      lymphangiography has shown abnormal collecting lymphatics in some patients with
      YNS. In this study, lymphatic function in the upper and lower limbs of 17
      patients with YNS, in normal controls, and in patients with established classical
      lymphoedema, has been assessed using quantitative lymphoscintigraphy. Nine
      subjects with YNS had swelling of the legs and two had features typical of
      lymphoedema. The lymphatic drainage was significantly reduced in the legs of
      patients with YNS but not to the level seen in lymphoedema. Lymphatic function
      was also reduced in the arms in patients with YNS. Venous insufficiency did not
      contribute to the leg oedema. These results suggest that the underlying cause of
      YNS is not primarily a lymphatic abnormality. The lymphatic impairment associated
      with YNS appears to be secondary, and predominantly functional in nature, rather
      than due to structural changes.

PMID- 8746348
TI  - What do general practitioners want from a dermatology department?
AB  - Four hundred and fifty-six practitioners (GPs) in Avon were asked what they
      required from their department of dermatology, and what improvements to the
      present service they could suggest. Most GPs preferred to manage the majority of
      dermatological problems themselves, with support from the department where
      necessary. They referred to a hospital department because they lacked the
      necessary expertise, but would prefer to receive training, advice and support in
      managing their patients rather than surrender long-term care to a specialist
      department. Despite this expressed willingness to shoulder more of the
      dermatological burden, only 31% of the GPs had received any postgraduate training
      in dermatology. In fact 57% said they had little interest in the subject and had
      not attended any form of dermatology teaching since qualifying. GPs would also
      like more guidance in the form of regularly updated guidelines and protocols, and
      easy access to dermatologists for telephone advice at regular fixed times. Some
      also felt that consultants should aim to provide diagnosis, investigation, and
      management guidelines for referred patients after a single visit. These findings
      should prompt a re-appraisal of the relative roles of GP and dermatologist, and
      emphasize the need for vocational training and continuing medical education in
      dermatology for all GPs.

PMID- 8746350
TI  - Histochemical and ultrastructural study of diffuse melanoderma after bone marrow
      transplantation.
AB  - Hyperpigmentation is a well-recognized feature of cutaneous graft-versus-host
      disease (GVHD), and is usually restricted to sites where lichenoid or
      sclerodermiform lesions have occurred. Since 1975, two of 745 patients treated by
      allogeneic bone marrow transplantation in our institution have developed diffuse
      melanoderma which differed considerably from the classic presentations. They both
      developed acute GVHD, then lichen planus-like chronic lesions and diffuse
      melanoderma. Histology of biopsies of the pigmented skin showed intense pigment
      deposition in the basal and suprabasal layers, and in dermal macrophages. On
      split-dopa, melanocyte counts were 98 and 93 per field, respectively. Electron
      microscopy showed melanocytes protruding into the dermis, and dark melanosomes in
      all epidermal layers and in macrophages. These findings were suggestive of post
      inflammatory hyperpigmentation. In bone marrow recipients, de novo melanoderma is
      a rare event which could represent a feature of cutaneous GVHD in pigmented
      subjects.

PMID- 8746349
TI  - Hypotrichosis, hair structure defects, hypercysteine hair and glucosuria: a new
      genetic syndrome?
AB  - Structural hair changes may be the expression of a genetic disorder affecting
      hair growth, part of a congenital syndrome with accompanying hair malformations,
      or a marker for an underlying metabolic disorder. We report a 22-month-old
      Turkish girl and her 10-month-old brother, whose scalp hair became fragile and
      sparse at about 6-7 months of age. Glucosuria, without diabetes or kidney
      disease, was detected 3-4 months later. Clinical examination revealed normal
      physical and mental development, and an analysis of plucked hairs showed
      dysplastic and broken hair shafts. Polarizing microscopy and scanning electron
      microscopic studies revealed torsion, and irregularities and impressions of the
      hair shaft, as seen in pili torti, trichorrhexis nodosa and pseudomonilethrix.
      Analysis of the amino-acid composition of the hair demonstrated a significant
      reduction of sulphonic cysteic acid and an elevated cysteine and lanthionine
      content in the girl, and elevated lanthionine levels in her brother.
      Electrophoretic analysis of the girl's hair proteins revealed a normal
      composition but a high extractability of hair proteins. The triad of
      hypotrichosis, structural hair-shaft defects and abnormal amino-acid composition,
      accompanied by glucosuria without diabetes, may represent a new genetic syndrome.

PMID- 8746351
TI  - Extracorporeal photochemotherapy in a patient with Ki-1-positive anaplastic large
      cell lymphoma.
AB  - A 57-year-old man with Ki-1 anaplastic large-cell lymphoma treated with
      extracorporeal photochemotherapy is described.

PMID- 8746352
TI  - A case of linear IgA bullous dermatosis with IgA anti-type VII collagen
      autoantibodies.
AB  - In this study we present a patient with the sublamina densa type of linear IgA
      bullous dermatosis (LABD), with IgA autoantibodies reactive with the 290-kDa type
      VII collagen (the epidermolysis bullosa acquisita (EBA) antigen) and with
      immunoblotting of normal human dermal extracts. The clinical and histological
      features of the present case were compatible with those of LABD but quite
      different from those of EBA. Although EBA sera reacted with the bacterial fusion
      protein of the N-terminal globular (NC1) domain of type VII collagen, this
      patient's serum did not show reactivity. Furthermore, ultrastructural
      localization of target epitopes on the anchoring fibrils in this patient was
      considerably different from EBA. These results indicate that, whereas EBA
      antibodies react with the NC1 domain of type VII collagen, the epitope in this
      case is different from that of EBA (and is most likely on the central triple
      helical domain). This difference may be responsible for the clinical presentation
      in this patient being distinct from that of EBA.

PMID- 8746353
TI  - Coexistence of psoriasis and an unusual IgG-mediated subepidermal bullous
      dermatosis: identification of a novel 200-kDa lower lamina lucida target antigen.
AB  - Bullous pemphigoid (BP) is characterized by autoantibodies against 230- and 180
      kDa hemidesmosomal antigens located in the most superficial layers of the
      basement membrane zone (BMZ). Histologically, there is a predominance of
      eosinophils in the infiltrate. In a psoriatic patient, we identified an unusual
      autoimmune subepidermal bullous eruption which clinically resembled BP, but which
      was characterized by IgG autoantibodies against a novel 200-kDa lower lamina
      lucida component. Histologically there was a predominance of neutrophils in the
      infiltrate. Direct immunofluorescence showed linear immunoglobulin (Ig)G and C3
      deposition at the BMZ. The patient's IgG autoantibodies bound exclusively to the
      dermal side of salt-split normal human skin. Indirect immunogold electron
      microscopy showed a marked deposition of IgG at the lower lamina lucida and
      minimal deposition at the hemidesmosomes. Immunoblot analysis identified a unique
      200-kDa autoantigen in dermal extracts and a faint band of the 230-kDa BP antigen
      in epidermal extracts. The patient responded dramatically well to cyclosporin A.
      Although the patient's serum also reacted slightly with the 230-kDa BP antigen,
      there were significant findings different from the usual immunopathological
      changes of BP. These included finding a novel 200-kDa lower lamina lucida target
      antigen, the binding of IgG autoantibodies exclusively to the dermal side of the
      split skin and a predominance of neutrophils in blister infiltrate. The IgG
      autoantibodies against the 200-kDa lamina lucida target antigen seemed to play a
      major role in the pathogenesis of this unique autoimmune subepidermal dermatosis.

PMID- 8746354
TI  - Oral psoriasis.
AB  - We present a patient with oral lesions consistent with a diagnosis of oral
      psoriasis and discuss the relationship of oral and skin lesions in psoriasis.

PMID- 8746355
TI  - Scrofuloderma (tuberculosis colliquativa cutis).
AB  - A 16-year-old girl presented with long-standing purulent sinuses to the skin
      overlying the lacrimal ducts, which had evolved into ulcers and resulted in
      hypertrophic scarring. The ulcers were serpiginous, with an uneven soft floor,
      and undermined edges. Histological examination revealed non-caseating tuberculoid
      granulomas in the dermis. Cultures for Mycobacterium tuberculosis were positive.
      Chest X-ray did not show pulmonary involvement. Antituberculous therapy with
      isoniazid 300 mg/day and rifampicin 600 mg/day achieved a great improvement
      within 5 weeks of being started. A further improvement was seen at 4 months and
      complete resolution had occurred by 9 months. To the best of our knowledge, there
      are no other documented cases of scrofuloderma over the lacrimal system. The
      delay in the diagnosis emphasizes the importance of maintaining a high level of
      awareness.

PMID- 8746356
TI  - Persistent erythema and pruritus, with a confluent histiocytic skin infiltrate,
      following the use of a hydroxyethylstarch plasma expander.
AB  - A 40-year-old woman developed a persistent pruritus with erythema of the head and
      upper trunk, which started within 2 weeks of a hydroxyethylstarch (HES) infusion
      and was still present 2 years later. Histological examination demonstrated a
      striking dermal infiltrate of KP1-positive foamy macrophages which had electron
      lucent vacuoles. The timing of the onset, the body site distribution, the
      exclusion of other possibilities and an appropriate history of high dosage HES
      infusion, suggested that this was the cause of the eruption. Staining with
      periodic acid-Schiff (PAS) surprisingly was negative but we could not stain HES
      in vitro with this histochemical stain, and we postulate that the unique extent
      of the infiltrate and the negative PAS stain in our patient may indicate an
      impaired ability to degrade this chemical. This may be an important factor in the
      poorly understood pathogenesis of persistent pruritus induced by HES.

PMID- 8746357
TI  - Lichen planus-like contact dermatitis due to methacrylic acid esters.
AB  - We report a patient who had lichen planus-like lesions on sites repeatedly
      exposed to methacrylic acid esters used in the car industry. Histologically, the
      lesions showed all the features of classical lichen planus. Patch testing
      revealed positive reactions to methacrylic acid esters in concentrations as low
      as 5 x 10(-3)%. As dental devices contain methacrylic acid esters, it is possible
      to speculate that methacrylic acid esters may be one of the causative agents for
      oral lichen planus.

PMID- 8746358
TI  - Vasculitis attributed to the nicotine patch (Nicotinell).
AB  - Nicotine-containing patches are used to facilitate tobacco withdrawal by
      mitigating abstinence symptoms and diminishing craving. We describe two patients
      who developed vasculitis in association with the use of a nicotine patch. The
      first concerns a patient who developed fever, arthritis, a generalized erythema
      and purpuric lesions, after 3 days use of nicotine patches. Laboratory results
      and a skin biopsy confirmed the diagnosis of a leucocytoclastic vasculitis. After
      stopping use of the patch, the patient recovered. On challenge, the symptoms
      reappeared. The second patient developed purpuric lesions during the use of
      nicotine patches, and recovered fully after these were stopped. In these
      patients, nicotine patches seem to be causally related to the development of
      vasculitis.

PMID- 8746359
TI  - Eruptive vellus hair cysts and steatocystoma multiplex. variants of one entity?
AB  - Eruptive vellus hair cysts and steatocystoma multiplex are two clinically similar
      conditions which show multiple papules and nodules, mainly located over the
      anterior chest wall. Most cases can be differentiated on histological
      examination, but in some patients overlapping histological features have been
      described. We present a patient who showed features of both entities and
      interpret this as suggesting that eruptive vellus hair cysts and steatocystoma
      multiplex are variants of one disorder which originates in the pilosebaceous
      duct.

PMID- 8746360
TI  - Pilomatrix carcinoma and multiple pilomatrixomas.
AB  - Pilomatrixoma is the only skin appendage tumour showing predominantly hair matrix
      differentiation. Rarely, aggressive or malignant variants are reported in the
      literature. We report a case of a 44-year-old male with multiple pilomatrixomas,
      one of which grew rapidly, recurring several times. Histological examination of
      this tumour showed predominantly hair matrix differentiation but also abortive
      hair follicle formation with pilar keratinization reminiscent of a
      trichoepithelioma. Numerous mitoses and moderate cellular pleomorphism were
      present, associated with infiltration of subcutaneous skeletal muscle and
      vascular invasion.

PMID- 8746361
TI  - Melanoma awareness and sun exposure in Leicester.

PMID- 8746362
TI  - Hydroxychloroquine and chronic erythema nodosum.

PMID- 8746363
TI  - Vitiligo.

PMID- 8746364
TI  - P53 expression and human papillomavirus infection in transplant recipients and in
      patients with epidermodysplasia verruciformis.

PMID- 8746365
TI  - Renal impairment associated with oral terbinafine.

PMID- 8746366
TI  - Melanonychia due to Candida humicola.

PMID- 8746367
TI  - Spontaneous regression of congenital multiple median raphe cysts of the raphe
      scroti.

PMID- 8746368
TI  - Loss of taste associated with isotretinoin.

PMID- 8746369
TI  - Fingertip necrosis during chemotherapy with bleomycin, vincristine and
      methotrexate for HIV-related Kaposi's sarcoma.

PMID- 8746370
TI  - Prurigo pigmentosa associated with ketosis.

PMID- 8746371
TI  - Confluent and reticulated papillomatosis associated with atopy. Successful
      treatment with topical urea and tretinoin.

PMID- 8746372
TI  - Multivariate determination of glucose concentrations from optimally filtered
      frequency-warped NIR spectra of human blood serum.
AB  - Glucose concentrations over the 39-160 mg dl-1 range have been determined from
      357 NIR (near-infrared) spectra of human blood serum in the spectral region from
      6766 cm-1 to 4003 cm-1. A frequency-warping procedure was applied to the NIR data
      to compress 511 spectral components into 102 in the 6766-4003 cm-1 spectral
      region. Before the data compression process was carried out, the NIR spectrum of
      deionized water was subtracted from each of the blood serum spectra to remove the
      intrinsic high background absorption due to the water. PLS (partial least
      squares) regression was coupled with time-domain digital Butterworth bandpass
      filtering in an optimization procedure. The optimization procedure was carried
      out over a range of centre frequencies and bandwidths for first- (two-pole),
      second- (four-pole) and third- (six-pole) order bandpass filters, and over a
      range of PLS factors. The optimal PLS model and filter parameters were determined
      from a sequence of three-dimensional performance response maps for different
      numbers of PLS factors and filter orders. As a basis for comparison, the same
      optimization process was carried out for a Gaussian filter design approach (i.e.,
      Fourier filtering). Using the optimally filtered frequency-warped NIR spectral
      data, an SEP (standard error of prediction) of 13.2 mg dl-1 was achieved fro the
      test (monitoring) data using 14 PLS factors and a simple first-order (two-pole)
      digital Butterworth bandpass filter.

PMID- 8746373
TI  - Determination of the relationship between the pH and conductivity of gastric
      juice.
AB  - Studies of gastric secretion were carried out on 14 subjects, some of whom had
      taken acid secretion inhibitors. In vitro studies were performed in an attempt to
      ascertain the effect of H+ and Na+ ions on conductivity. There is a strong
      correlation between intragastric pH and conductivity for pH < 2, but none of the
      gastric samples were isotonic. The measured conductivity of the samples was
      therefore considerably lower than predicted for isotonic gastric juice.

PMID- 8746374
TI  - The lowering of stroke volume measured by means of impedance cardiography during
      endexpiratory breath holding.
AB  - Impedance cardiography is a reliable method for estimating stroke volume (SV).
      Breathing, however, causes artefacts, which can be avoided by measuring during
      breath holding. This study investigated whether SV determination is accurate
      during breath holding. Twelve healthy subjects were tested in the supine position
      at rest and during two levels of exercise: 100 and 200 W. Averaged SV values were
      monitored by means of impedance cardiography before and after endexpiratory
      breath holding. During breath holding, SV measurement was on a beat-to-beat
      basis. An obvious decrease in SV during breath holding was noticed, being
      significant only during exercise (mean decrease of 38% at 100 W and 58% at 200
      W). The rest measurements were repeated with open and closed glottis, which
      yielded the same results. This indicates that the SV decrease was not caused by a
      Valsalva-like manoeuvre. The mean SV value calculated by means of impedance
      cardiography for the total breath hold period was significantly lower than the SV
      during breathing, both at rest (91.7 +/- 2.4%) and at 100 W (90.5 +/- 7.0%). From
      this study it can be concluded that averaging of the impedance signal, measured
      while the subject is breathing, is preferential to measuring during breath
      holding, because the latter condition systematically underestimates SV.

PMID- 8746375
TI  - Early measurement of lung volume--a useful discriminator of neonatal respiratory
      failure severity.
AB  - Respiratory distress syndrome (RDS) is characterized by lungs having collapsed
      alveoli (atelectasis) which reduces the volume of the gas-containing spaces of
      the lung. It seems likely, therefore, that measurement of lung volume might
      discriminate between infants with severe respiratory failure due to RDS and those
      with minimal respiratory distress. To test this hypothesis, lung volume was
      measured at end expiration, that is functional residual capacity (FRC), in 40
      infants (median gestational age 29 weeks, range 24-35) all mechanically
      ventilated from birth. FRC was measured using a helium gas dilution technique at
      a median of 3 h of age. The infants were divided into two groups according to
      their FRC results: group A (n = 29) low FRC (FRC < 24 ml kg-1) and group B (n =
      11) normal FRC (FRC > or = 24 ml kg-1). The clinicians were unaware of the FRC
      results. There was no significant difference in the gestational age or
      birthweight of the two groups, but group A were characterized by a significantly
      greater proportion requiring surfactant replacement therapy (p < 0.01), a higher
      maximum peak inspiratory pressure (p < 0.01) and inspired oxygen requirement (p <
      0.01). A low FRC had 79% sensitivity and 91% specificity in predicting a
      requirement for surfactant replacement therapy. We conclude that measurement of
      FRC in the first hours of life does allow discrimination of disease severity.

PMID- 8746376
TI  - The performance of a variable-flow indirect calorimeter.
AB  - Indirect calorimetry estimates energy expenditure from measurement of respiratory
      gas exchange volumes. This paper considers the design and evaluation of an
      indirect calorimeter, the Europa GEM, suitable for use in nutritional research.
      The calorimeter is of the ventilated hood, flow-through type and is intended for
      use with spontaneously breathing patients. Our aim was to develop an accurate,
      flexible instrument with a high level of automation. Performance was assessed in
      a laboratory simulation using reference gas injections (n = 24) producing a mean
      error of 0.3 +/- 2% in oxygen consumption (VO2), 1.8 +/- 1% in carbon dioxide
      production (VCO2) and 1.4 +/- 1.5% in respiratory quotient (RQ). In order to
      investigate the effect of FeCO2 on error multiplication a further subdivision (n
      = 8) of tests at FeCO2 = 0.5%, 0.75% and 1% was made by modulating the air flow
      through the hood. However, the predicted increase in system accuracy with
      increasing FeCO2 was not apparent in practice.

PMID- 8746377
TI  - Foot surgery in the patient with diabetes.
AB  - Foot surgery for the patient with diabetes does not need to have negative
      implications. Limb salvage is always a worthwhile goal. The surgeon needs to
      consider prophylactic surgery in the patient with diabetes to prevent subsequent
      infections from developing in pressure areas. The assessment of hypoxia, with the
      help of a vascular surgeon when necessary, is of obvious importance. The large
      number of misconceptions regarding foot surgery for patients with diabetes leads
      to considerable confusion regarding surgical care. Many patients with diabetes
      recover from infections, as well as elective and ablative surgery. This may
      enable years of foot function to be preserved and is a worthwhile goal in all
      foot surgery involving patients with diabetes.

PMID- 8746378
TI  - The shod foot and its implications for American women.
AB  - Throughout history, members of human societies have gone barefoot, and those
      societies seemingly had a low incidence of foot deformities and pain. Only one
      study has addressed the problem of infection through injury to the bare foot;
      otherwise, the unshod foot seems to have had minimal problems. Initially shoes
      were made in the shape of the foot and were sandals. Over time, shoes became
      decorative items and symbols of status and vanity. As the shape of shoes changed,
      they became deforming forces on the foot and the source of pain. Recent studies
      by the Council on Women's Footwear of the American Orthopaedic Foot and Ankle
      Society have tried to document the problems caused by shoes on the feet of
      American women. Attempts should continue to educate women on appropriate shoes
      and proper fit.

PMID- 8746379
TI  - Hallux valgus due to cuneiform-metatarsal instability.
AB  - We present a biomechanical rationale for the treatment of severe hallux valgus
      deformity by realignment and arthrodesis of the first cuneiform metatarsal (CM)
      joint. We think that this severe hallux valgus deformity represents instability
      at the CM-1 articulation, since normal motion at that joint is very small. A
      forefoot compression test was used to assess the foot preoperatively. This was
      found not only to realign the first metatarsal, but also to align the
      metatarsophalangeal joint. A surgical procedure has evolved to include a
      transverse screw between the first and second metatarsal bases, as well as a
      second screw from first cuneiform to first metatarsal base, along with a small
      volume bone graft of the CM-1 articulation. This is a modern variant of the
      Lapidus procedure.

PMID- 8746380
TI  - Percutaneous diskectomy for disk space infections.
AB  - To diagnose and treat intervertebral disk space infection, we used percutaneous
      diskectomy in four patients to harvest a large amount of disk material and to
      decompress and lavage the infected disk space with a broad spectrum antibiotic
      solution. This treatment regimen rapidly diminished pain and shortened the acute
      clinical course of the process. The long-term course in this small number of
      patients, however, appears not to have been altered.

PMID- 8746381
TI  - Flexion and extension gap measurements in total knee arthroplasty after sacrifice
      of posterior cruciate ligament.
AB  - Twenty-three patients had 25 total knee arthroplasties. The flexion and extension
      gaps were measured before and after resection of the posterior cruciate ligament.
      The extension gap increased 2.0 +/- 0.2 mm in the medial compartment and 1.9 +/-
      0.3 mm in the lateral compartment. The flexion gap increased 1.4 +/- 0.2 mm in
      the medial compartment and 2.3 +/- 0.3 mm in the lateral compartment. All
      increases were statistically significant.

PMID- 8746382
TI  - Total joint replacement in active golfers.
AB  - Total joint replacement is commonly done in an older population, for whom golf is
      often the only form of exercise. We studied active golfers after they had had a
      total joint replacement. Most golfers with a successful primary total joint
      replacement will not have pain while playing golf, but will likely have a mild
      ache in the hip or knee region after playing. Patients with total knee
      replacement appear to have slightly more postgolf pain than patients with total
      hip replacement. In addition, golfers with left total knee replacements have more
      difficulty with pain during and after play than do golfers with right total knee
      replacements.

PMID- 8746383
TI  - Orthofix external fixation of distal radius fractures: complications associated
      with screw size.
AB  - We did a retrospective analysis of 28 patients who were treated with the Orthofix
      external fixation system for complex fractures of the distal radius to study
      complications associated with screw size. The 14 patients in group 1 had a
      4.5/3.5-mm tapered screw placed in the metacarpal bone; the 14 patients in group
      2 had a 3.5/3.3-mm tapered screw placed in the metacarpal bone. Both groups had
      4.5/3.5-mm tapered screws placed in the radius. Two patients in group 1 had
      metacarpal pin tract infections; no patients in group 2 had a distal pin tract
      infection. Two patients in group 1 had a fracture of the metacarpal; only one
      patient in group 2 had a fracture of the metacarpal. In both groups two patients
      had proximal pin tract infections at the radius screw fixation site. There was no
      screw breakage in either group. The unique design of the tapered Orthofix screw
      allows it to be removed almost painlessly in the clinic. At installation in the
      operating room, however, the surgeon must remember not to back the threaded pin
      out for fine adjustment of bony penetration. Any reverse excursion of the
      threaded shaft will loosen the tapered screw and cause early failure of the
      fixation. We no longer use the 4.5/3.5-mm screw when managing wrist fractures
      with the Orthofix external fixation system. It is now our policy to use the
      3.5/3.3-mm screw for fixation of the Orthofix external frame to both the
      metacarpal bone and the radius.

PMID- 8746384
TI  - Injury to a soccer player.

PMID- 8746385
TI  - Reflections on a career in foot and ankle care: Basil M. Boyd, Jr., MD Miller
      Orthopaedic Clinic 1958-1992.

PMID- 8746386
TI  - Fractures of the distal radius in adults.

PMID- 8746387
TI  - Comparative effects of modafinil and amphetamine on daytime sleepiness and
      cataplexy of narcoleptic dogs.
AB  - The effects of modafinil and amphetamine on daytime sleep (polysomnographic
      recordings) and cataplexy (the food-elicited cataplexy test) were compared using
      the narcoleptic canine model. Results indicate that both modafinil (5 and 10
      mg/kg body weight i.v.) and amphetamine (100 and 200 micrograms/kg i.v.) increase
      wakefulness and reduce slow-wave sleep in control and narcoleptic dogs. In
      contrast, the results of cataplexy testing demonstrate that amphetamine (2.5-160
      micrograms/kg i.v.), but not modafinil (0.125-8.0 mg/kg i.v.) significantly
      suppresses canine cataplexy. These results suggest that the pharmacological
      property of modafinil is distinct from amphetamine. Results of polysomnographic
      recordings also demonstrate that narcoleptic dogs slept significantly more during
      the daytime than control dogs and required very high doses (10 mg/kg i.v.
      modafinil; 200 micrograms/kg i.v. amphetamine) of stimulants to reduce their
      level of sleepiness to that of control dogs. This finding is consistent with the
      data collected in human narcolepsy and validates the use of this canine model for
      the screening of stimulant compounds.

PMID- 8746388
TI  - What does the multiple sleep latency test measure in a community sample?
AB  - Multiple sleep latency test (MSLT)-defined daytime sleepiness and its
      relationships with nocturnal and daytime psychophysiological activation were
      investigated in a random community sample of 77 subjects aged 35-55 years. The
      correlation structure between all study variables was explained by a simple model
      of daytime sleepiness. The model suggested that indicators of psychophysiological
      arousal (psychological distress, nocturnal motor activity and serum thyrotropin
      level) and daytime reported tiredness, body mass index (BMI) and age were related
      significantly and independently to MSLT-defined daytime sleepiness. The arousal
      theory of insomnia and poor sleep in relation to MSLT behavior is discussed and
      the need of a multivariate approach is emphasized in MSLT studies.

PMID- 8746389
TI  - Comparison of a frequency-based analysis of electroencephalograms (Z-ratio) and
      visual scoring on the multiple sleep latency test.
AB  - In a sample of multiple sleep latency test naps following nocturnal
      polysomnograms from a group of 13 patients of varying ages and diagnoses, we
      compared a computer-derived electroencephalographic (EEG) measure (z-ratio) with
      standard visual sleep stage scoring. In this clinical population, z-ratio scoring
      agreed with human scorers approximately 80% of the time when determining sleep
      versus wake in 30-second epochs. These results show that a single, objectively
      quantifiable value derived from a single channel of EEG can distinguish between
      sleep and wakefulness (as defined by Rechtschaffen and Kales) with at least a
      moderate degree of precision. When refined, the z-ratio method might be of use as
      the basis for a new sleep scoring system, particularly where an accurate
      determination of sleep onset is required.

PMID- 8746390
TI  - Sleep disturbances in the demented elderly: treatment in ambulatory care.
AB  - We report the results of a representative survey in Lower Saxony, Germany, that
      focused on the treatment of sleep disturbances in the moderately demented
      elderly. Two written sample case histories (vignettes) described either a
      vascular demented patient suffering from nocturnal wandering or an Alzheimer's
      type demented patient without apparent psychotic or behavioral (sleep) disorder.
      These were randomly assigned and presented to 145 family physicians and 14
      neuropsychiatrists working in private practice by a trained investigator, who
      then conducted a standardized interview with the physicians. The study was
      representative of physicians (response rate: 83.2%). In response to the question
      concerning how they would treat the patient's sleep disturbances, about 20% of
      the physicians (with respect to both versions) answered that they would not
      choose drugs. More than 40% considered neuroleptics to be the drugs of choice.
      Benzodiazepines, antidepressants and other substances were seldom considered. No
      significant difference was noted in the response to the two different case
      histories. The results allow for the conclusion that non-drug treatments, which
      (at least initially) should be the treatment of choice, are mainly disregarded by
      the majority of the ambulatory care physicians. The reason for this seems to be a
      lack of education in sleep medicine and also in geriatric medicine.

PMID- 8746391
TI  - Precocious loss of physiological sleep in a case of Creutzfeldt Jakob disease: a
      serial polygraphic study.
AB  - Creutzfeldt-Jakob disease (CJD) is a prion-related subacute encephalopathy
      producing widespread neuronal degeneration and spongiform pathological changes,
      especially in the neocortex. Progressive dementia, motor signs and
      electroencephalographic (EEG) alterations characterize the full stage of the
      disease. A series of eight 24-hour polygraphic recordings were carried out in the
      last 3 months of life of a 68-year-old female patient affected by CJD that was
      confirmed neuropathologically. Genetic classification demonstrated this patient
      to have a sporadic form of the disease. The polygraphic recordings demonstrated
      three types of EEG findings, as follows: 1) sustained pseudoperiodic discharges
      (SPD), characterized by long-lasting diffuse sequences of slow sharp waves or di-
      or triphasic slow waves recurring at 0.5- to 1.5-second intervals; 2)
      discontinuous pseudoperiodic discharges (DPD), consisting of runs of
      pseudoperiodic discharges (PD)(phase A) cyclically replaced at about 1-minute
      intervals with semi-rhythmic theta-delta activities (phase B); 3) non-rapid eye
      movement (NREM) sleep-like pattern, with dominant 0.5- to 4-Hz activities, less
      rhythmic than the EEG of phase B. Only these three EEG patterns occurred
      spontaneously during the repeated polygraphic sessions. The NREM sleep-like
      pattern was found only in the first recording, whereas the following polygraphic
      sessions were occupied exclusively by SPD or by a DPD pattern. SPD was associated
      with either a relatively high level of vigilance (along the first three
      recordings) or a state of alert-appearing silent immobility (following the fourth
      recording). During DPD, the patient was unable to accomplish any voluntary
      movement and fluctuated between levels of greater arousal (phase A) and lesser
      arousal (phase B). Just as in stage 2 coma, the fluctuations between phases A and
      B of DPD were synchronous with phasic modifications of muscle activity and
      neurovegetative functions. In particular, reinforcement of muscle tone and
      myoclonic spasms coincided with phase A, whereas heart rate deceleration and
      respiratory pauses or decrease in flow were synchronous with phase B. As EEG
      evolved toward the disappearance of DPD and finally to flatness, the phase-locked
      coordination among arousal, somatic and vegetative activities was progressively
      impaired and was replaced with an uncontrolled exaggeration of cardiorespiratory
      activity. The genetic, neuropathological and polysomnographic differences between
      CJD and another prion disease, fatal familial insomnia, are discussed.

PMID- 8746392
TI  - The effect of hypoxia on baroreflexes and pressor sensitivity in sleep apnea and
      hypertension.
AB  - Many persons with sleep apnea are hypertensive. Forty-two subjects of similar age
      and weight were divided into four groups of hypertensives and normotensives with
      and without sleep apnea. All subjects had heart rate, blood pressure (BP),
      baroreflex sensitivity and pressor sensitivity to phenylephrine measured while
      breathing room air or 15% oxygen. Hypoxia raised heart rate and lowered BP in all
      groups (p < 0.001), with the greatest hypotensive effect among hypertensives.
      Hypertensives had blunted baroreflex sensitivity, and breathing a hypoxic mixture
      lowered baroreflex sensitivity of all four groups (p = 0.008). The apneic
      subjects tended to lower their baroreflex sensitivity more in response to hypoxia
      and also had an enhanced pressor response to phenylephrine, whether breathing
      room air or 15% oxygen. Episodes of sleep apnea lead to hypoxia, an initial
      period of hypotension and a subsequent increase in sympathetic nervous activity.
      Our studies suggest that apneics could have an exaggerated pressor sensitivity to
      norepinephrine. They might also have difficulty returning BP to normal levels,
      because hypoxia impaired baroreflexes.

PMID- 8746393
TI  - Snoring and arousals: a retrospective analysis.
AB  - The purpose of this retrospective analysis was to search for possible
      associations between snoring and arousals. We searched our data base containing
      more than 2,000 records and selected only patients who 1) had objective
      measurements of snoring, 2) were not taking sedating medication, 3) did not have
      sleep apnea (apnea/ hypopnea index < 10) and 4) did not have periodic leg
      movements (myoclonus index < 5). This procedure left 367 patients available for
      analysis. We hypothesized that arousals observed in these patients were
      associated with snoring, and we performed univariate and multivariate regression
      analysis with arousals as the dependent variable, and age, body mass index,
      snoring, maximum nocturnal sound intensity and nocturnal oxygen saturation as the
      independent variables. The results showed that only snoring and mean nocturnal
      oxygen saturation were significant (p < 0.05) but weak determinants of arousals,
      accounting for only 7% of their variance. To examine whether snorers have more
      arousals than non-snorers, we compared a control group of non-snorers (< 50
      snores/hour of sleep), with a group of heavy snorers (> 400 snores/hour of
      sleep). We found that the arousal index was significantly but weakly higher in
      snorers than non-snorers [mean +/- standard deviation (SD) = 14 +/- 8 vs. 10 +/-
      6, p < 0.002]. Conversely, patients within the highest arousal quartile snored
      significantly more than those within the lowest quartile (snoring index 293 +/-
      292 vs. 179 +/- 282, p < 0.008, respectively). We conclude that despite the
      limitations of this retrospective analysis, there appears to be an association
      between snoring and arousals, warranting further, properly designed prospective
      studies.

PMID- 8746394
TI  - Comparison of cephalometric analysis with ethnicity in obstructive sleep apnea
      syndrome.
AB  - Many studies have documented significant craniomandibular abnormalities in
      obstructive sleep apnea syndrome (OSAS) patients. Recent literature clearly
      describes the cephalometric abnormalities commonly associated with OSAS. Studies
      have not evaluated specific cephalometric abnormalities that may contribute to
      OSAS by various ethnic groups. Data were collected on 48 patients (20 Caucasian,
      15 Black and 13 Hispanic) with completed cephalometric analysis and
      polysomnography. Cephalometric landmarks, angles and measurements [angle measured
      from sella to nasion to subspinale point (SNA), angle measured from sella to
      nasion to supramentale point (SNB), difference between SNA and SNB (ANB),
      perpendicular distance from gonion to gnathion to hyoid (MP-H), distance from
      posterior nasal spine to tip of soft palate (PNS-P) and posterior airway space
      (PAS)] commonly used in the evaluation of OSAS patients were recorded.
      Measurements were normalized by dividing the observed value by the mean value for
      the ethnic group. Statistically significant differences in normalized SNA and SNB
      appeared in the Black and Hispanic groups when compared to the Caucasian group.
      For both SNA and SNB, Blacks averaged approximately 3.5% above their ethnic mean,
      whereas Hispanics averaged 1.8-2.8% below their ethnic mean. There was a
      statistically significant correlation between respiratory distress index (RDI)
      and MP-H. These baseline cephalometric differences in the ethnic groups studied
      suggest that surgical intervention might be approached differently in various
      ethnic groups. Further studies that evaluate the surgical success achieved by
      various procedures among different ethnic groups may help define surgical
      protocol in various ethnic groups for OSAS.

PMID- 8746395
TI  - Measurement of general health status in obstructive sleep apnea hypopnea
      patients.
AB  - Sleep apnea hypopnea syndrome (SAHS) is an entity that occurs frequently in the
      population and produces an elevated morbidity and mortality, especially at an
      apnea index greater than 20 events per hour. To our knowledge there are only a
      few studies available addressing the general health status of sleep apnea
      hypopnea patients. Such information may be useful for both clinical management
      and better understanding of the physiopathological mechanisms of the disease,
      particularly with the consideration that not infrequently the physiological
      disturbances found in such patients do not always agree with their own health
      perception. Therefore, the aim of the present study was to assess the general
      health status and the degree of daytime somnolence, as a major symptom in SAHS
      patients, and relate them to the number of respiratory events per hour.
      Measurements of general health status and the degree of daytime somnolence were
      assessed in 103 consecutive patients 50.4 +/- 12 years old [mean +/- standard
      deviation (SD)] with an apnea/hypopnea index (AHI) of 38 +/- 27 events per hour.
      Forty nonsnoring healthy subjects were used as the control group. During the
      afternoon preceding the full polysomnography, a medical history was taken; basic
      anthropometric data and the presence of other diseases were recorded. The
      Nottingham Health Profile (NHP) questionnaire and a questionnaire assessing the
      degree of daytime somnolence were administered to the patients. No significant
      differences were found in the general health status and the degree of daytime
      hypersomnolence when patients were divided into three groups according to the
      severity of the respiratory events during the night, but there were significant
      differences between SAHS patients and control subjects. It was concluded that in
      spite of the fact that SAHS patients showed a deterioration of general health
      status parameters in comparison with healthy subjects, these parameters do not
      correlate with the physiological disturbances of SAHS, expressed as the number of
      respiratory events per hour.

PMID- 8746396
TI  - Topographical and temporal patterns of brain activity during the transition from
      wakefulness to sleep.
AB  - Changes in electroencephalographic (EEG) spectral power, coherence and frequency
      were examined for the last minute of wakefulness and the first minute of sleep
      via topographical mapping. Data were also analyzed across sequential 1-minute
      samples of wake, stage 1 and stage 2 sleep. Not all brain regions exhibited the
      same EEG changes during the transition and not all brain regions were found to
      change at the same time. Brain sites closest to the midline (e.g. F4, C4, P4, O2)
      showed significant changes in EEG power (increases in theta and decreases in
      alpha power) during the transition to sleep, whereas brain sites most lateral to
      the midline (e.g. Fp2, F8, T4) showed little change. Decreases in alpha coherence
      were observed from wakefulness to sleep for brain site comparisons furthest away
      from each other (e.g. T3 vs. T4, T5 vs. T6, F7 vs. F8, F3 vs. O1, F4 vs. O2).
      Spectral analysis of EEG activity revealed that the time of significant change in
      EEG power varies among brain regions. Decreases in alpha power continued to occur
      later into the transition period for the posterior regions of the brain (O2, P4).

PMID- 8746397
TI  - Power density in theta/alpha frequencies of the waking EEG progressively
      increases during sustained wakefulness.
AB  - Electroencephalogram (EEG) power density and self-rated fatigue were assessed in
      nine healthy women during a 40-hour period of sustained wakefulness under
      constant behavioral and environmental conditions (constant routine protocol).
      Waking EEG recordings were performed for 4 minutes after 3, 10, 27 and 34 hours
      of prior wakefulness. EEG power density in the 6.25- to 9.0-Hz frequency range
      progressively increased across the four recordings, suggesting an endogenous
      homeostatic component in the regulation of the theta/alpha frequencies under
      constant conditions. Subjective fatigue also exhibited an increasing component in
      the course of the constant routine protocol, with a clear circadian modulation.
      Fatigue ratings and the theta/ alpha power density of the waking EEG recorded at
      the same four time points during the constant routine protocol correlated
      significantly. Our data demonstrate the presence of a homeostatic component in
      the control of EEG power density in the 6.25- to 9.0-Hz range.

PMID- 8746398
TI  - Does a subtropical climate imply a seasonal rhythm in REM sleep?
AB  - The present study was performed on 615 male subjects referred to the Sleep
      Medicine Center at Tel Hashomer, Israel, and polysomnographically recorded for a
      single night between January 1, 1990 and December 31, 1993. The study suggests
      the existence of a circannual rhythm of rapid eye movement (REM) sleep time with
      an acrophase during December-January and a nadir during July-September (single
      cosinor analysis: mesor = 49.7 +/- 0.9, amplitude = 5.9 +/- 1.2, p < 0.001). Both
      REM sleep time and REM sleep percentage were higher and REM sleep latency shorter
      during winter and spring than during summer and fall. No dependence of the
      seasonal REM sleep time rhythm upon age, apnea-hypopnea index or diagnosis type
      was detected. These data support, for a subtropical climate, results previously
      obtained in a temperate climate. It is possible that external temperature may be
      the principal factor influencing the phenomenon.

PMID- 8746399
TI  - Should we be taking more sleep?
AB  - Reports of reduced daytime sleepiness following extended nighttime sleep in
      normal, regular sleepers suggest that they (and perhaps much of the general
      population) are chronically sleep deprived. However, 1) the social and
      environmental contexts of sleep allow for much intraindividual variation in sleep
      duration and structure; 2) animal studies show that when there is opportunity for
      sleep and few incentives to remain awake, sleep occurs for reasons other than in
      response to a physiological requirement, i.e. sleep satiation may precede actual
      awakening, 3) accounts of increased sleep duration earlier this century are
      flawed and 4) because increased sleep onset latency and wake after sleep onset
      are features of extended sleep, it would be difficult to persuade people to sleep
      longer for the small benefits to daytime alertness. Laboratory studies show that
      1) following extended sleep the improvements in daytime alertness are minor, even
      by the Multiple Sleep Latency Test (MSLT), and could be achieved equally
      successfully and with less disruption to habitual daily patterns by taking a
      short nap; 2) normal subjects extend sleep at night not necessarily because they
      are chronically sleepy, because there may be no prior MSLT signs of daytime
      sleepiness; 3) mood effects of extended sleep are confounded by earlier bedtimes;
      and 4) extended sleep does not necessarily make subjects feel well rested
      immediately on waking. In sum, most people are not chronically sleep deprived but
      have the capacity to take more sleep, in the same way that we eat and drink in
      excess of physiological needs.

PMID- 8746400
TI  - We are chronically sleep deprived.
AB  - Data from recent laboratory studies indicate that nocturnal sleep periods reduced
      by as little as 1.3 to 1.5 hours for 1 night result in reduction of daytime
      alertness by as much as 32% as measured by the Multiple Sleep Latency Test
      (MSLT). Other data document that 1) 17%-57% of normal young adults have MSLT
      latencies of < or = 5.5 minutes, whereas < or = 50% have MSLT values of > or = 10
      minutes and 2) 28%-29% of young adults reported normally sleeping < or = 6.5
      hours on each weeknight. More extensive reduction of daily sleep amount is seen
      in nightshift workers. A minimum of 2%-4% of middle-aged adults have
      hypersomnolence associated with sleep apnea. Together, these data show that
      significant sleep loss exists in one-third or more of normal adults, that the
      effects are large and replicable and that similar effects can be produced in just
      1 night in the laboratory. In light of the magnitude of this sleep debt, it is
      not surprising that fatigue is a factor in 57% of accidents leading to the death
      of a truck driver and in 10% of fatal car accidents and results in costs of up to
      56 billion dollars per year. A recent sleep extension study suggests that the
      average underlying sleep tendency in young adults is about 8.5 hours per night.
      By comparison, the average reported sleep length of 7.2-7.4 hours is deficient,
      and common sleep lengths of < or = 6.5 hours can be disastrous. We must recognize
      the alertness function of sleep and the increasing consequences of sleepiness
      with the same vigor that we have come to recognize the societal impact of
      alcohol.

PMID- 8746401
TI  - Sleep quality in Lyme disease.
AB  - Complaints of chronic fatigue as well as sleep disturbances are prevalent in Lyme
      disease. We compared polysomnographic measures of sleep in patients with
      documented Lyme disease with those of a group of age-matched normal control
      subjects. Eleven patients meeting Centers for Disease Control criteria for late
      Lyme disease with serologic confirmation by enzyme-linked immunosorbent assay and
      Western blot without a history of other medical or psychiatric illness and 10 age
      matched control subjects were studied. Lyme disease patients and controls
      underwent 2 nights of polysomnography. Multiple sleep latency testing (MSLT) was
      performed in the patients. Sleep was staged by standard criteria, and continuity
      of sleep was assessed for each stage of frequency analysis of consecutive epochs.
      All patients studied reported sleep-related complaints, including difficulty
      initiating sleep (27%), frequent nocturnal awakenings (27%), excessive daytime
      somnolence (73%) and restless legs/nocturnal leg jerking (9%). Greater sleep
      latency, decreased sleep efficiency and a greater arousal index were noted in
      Lyme patients. The median length of uninterrupted occurrences of stage 2 and
      stage 4 non-rapid eye movement (NREM) sleep was less in Lyme patients (6.3 +/-
      3.0 epochs in patients vs. 11.4 +/- 4.4 epochs in controls for stage 2, p < 0.01,
      and 4.3 +/- 4.4 epochs in patients vs. 11.2 +/- 6.3 epochs in controls for stage
      4, p < 0.01), indicating greater sleep fragmentation. Mean sleep onset latency
      during the MSLT was normal (12.7 +/- 5.6 minutes). Three patients demonstrated
      alpha-wave intrusion into NREM sleep. These sleep abnormalities may contribute to
      the fatigue and sleep complaints common in this disease.

PMID- 8746402
TI  - Model of synchronized population bursts in electrically coupled interneurons
      containing active dendritic conductances.
AB  - We constructed a computer model of 128 interneurons, each with multiple dendritic
      branches and an axonal segment. The model neurons were interconnected by gap
      junctions between dendritic compartments, as are known to occur in rat and guinea
      pig hilar interneurons. The model contained no excitatory synapses. In the
      presence of low-frequency spontaneous action potentials, the model generated
      synchronized population bursts, when gap junction resistance was 50 M omega and
      there were at least two gap junctions per neuron on average. Population bursts
      occurred only when the dendrites of model neurons were electrically excitable.
      Consistent with experiment, somatic hyperpolarization during the population burst
      uncovered partial spikes. In the model, partial spikes originated in electrically
      active dendrites driven by coupled dendrites. This model may account for
      population bursts in hilar interneurons that occur in 4-aminopyridine (4AP)
      together with blockers of GABAA and excitatory amino acid (EAA) receptors.

PMID- 8746403
TI  - Pyramidal cell-to-inhibitory cell spike transduction explicable by active
      dendritic conductances in inhibitory cell.
AB  - In the guinea-pig hippocampal CA3 region, the synaptic connection from pyramidal
      neurons to stratum pyramidale inhibitory neurons is remarkable. Anatomically, the
      connection usually consists of a single release site on an interneuronal
      dendrite, sometimes 200 microns or more from the soma. Nevertheless, the
      connection is physiologically powerful, in that a single presynaptic action
      potential can evoke, with probability 0.1 to 0.6, a postsynaptic action potential
      with latency 2 to 6 ms. We construct a model interneuron and show that the
      anatomical and physiological observations can be reconciled if the interneuron
      dendrites are electrically excitable. Excitable dendrites could also account for
      depolarization-induced amplification of the pyramidal cell-interneuron EPSP in
      the voltage range subthreshold for spike generation.

PMID- 8746404
TI  - A minimal, compartmental model for a dendritic origin of bistability of
      motoneuron firing patterns.
AB  - Various nonlinear regenerative responses, including plateau potentials and
      bistable repetitive firing modes, have been observed in motoneurons under certain
      conditions. Our simulation results support the hypothesis that these responses
      are due to plateau-generating currents in the dendrites, consistent with a major
      role for a noninactivating calcium L-type current as suggested by experiments.
      Bistability as observed in the soma of low- and higher-frequency spiking or,
      under TTX, of near resting and depolarized plateau potentials, occurs because the
      dendrites can be in a near resting or depolarized stable steady state. We
      formulate and study a two-compartment minimal model of a motoneuron that
      segregates currents for fast spiking into a soma-like compartment and currents
      responsible for plateau potentials into a dendrite-like compartment. Current
      flows between compartments through a coupling conductance, mimicking electrotonic
      spread. We use bifurcation techniques to illuminate how the coupling strength
      affects somatic behavior. We look closely at the case of weak coupling strength
      to gain insight into the development of bistable patterns. Robust somatic
      bistability depends on the electrical separation since it occurs only for weak to
      moderate coupling conductance. We also illustrate that hysteresis of the two
      spiking states is a natural consequence of the plateau behavior in the dendrite
      compartment.

PMID- 8746406
TI  - A model for long-term potentiation and depression.
AB  - A computational model of long-term potentiation (LTP) and long-term depression
      (LTD) in the hippocampus is presented. The model assumes the existence of
      retrograde signals, is in good agreement with several experimental data on LTP,
      LTD, and their pharmacological manipulations, and shows how a simple kinetic
      scheme can capture the essential characteristics of the processes involved in LTP
      and LTD. We propose that LTP and LTD could be two different but conceptually
      similar processes, induced by the same class of retrograde signals, and
      maintained by two distinct mechanisms. An interpretation of a number of
      experiments in terms of the molecular processes involved in LTP and LTD induction
      and maintenance, and the roles of a retrograde signal are presented and
      discussed.

PMID- 8746405
TI  - Rhythmically firing (20-50 Hz) neurons in monkey primary somatosensory cortex:
      activity patterns during initiation of vibratory-cued hand movements.
AB  - The activity patterns of rhythmically firing neurons in monkey primary
      somatosensory cortex (SI) were studied during trained wrist movements that were
      performed in response to palmar vibration. Of 1,222 neurons extracellularly
      recorded in SI, 129 cells (approximately 11%) discharged rhythmically (at
      approximately 30 Hz) during maintained wrist position. During the initiation of
      vibratory-cued movements, neuronal activity usually decreased at approximately 25
      ms after vibration onset followed by an additional decrease in activity at
      approximately 60 ms prior to movement onset. Rhythmically firing neurons are not
      likely to be integrate-and-fire neurons because, during activity changes, their
      rhythmic firing pattern was disrupted rather than modulated. The activity pattern
      of rhythmically firing neurons was complimentary to that of quickly adapting SI
      neurons recorded during the performance of this task (Nelson et al., 1991).
      Moreover, disruptions of rhythmic activity of individual SI neurons were similar
      to those reported previously for local field potential (LFP) oscillations in
      sensorimotor cortex during trained movements (Sanes and Donoghue, 1993). However,
      rhythmic activity of SI neurons did not wax and wane like LFP oscillations
      (Murthy and Fetz, 1992; Sanes and Donoghue, 1993). It has been suggested that
      fast (20-50 Hz) cortical oscillations may be initiated by inhibitory interneurons
      (Cowan and Wilson, 1994; Llinas et al., 1991; Stern and Wilson, 1994). We suggest
      that rhythmically firing neurons may tonically inhibit quickly adapting neurons
      and release them from the inhibition at go-cue onsets and prior to voluntary
      movements. It is possible that rhythmically active neurons may evoke intermittent
      oscillations in other cortical neurons and thus regulate cortical population
      oscillations.

PMID- 8746408
TI  - A search for genes predisposing to manic depressive illness on chromosome 20.
AB  - Very few studies have investigated linkage between manic depressive illness and
      markers from chromosome 20. Apparently no cytogenetic abnormalities involving
      chromosome 20 have been described in patients with affective disorders. Several
      interesting candidate genes of possible psychiatric relevance have been mapped to
      chromosome 20, including genes encoding a G-protein subunit and two enzymes
      involved in the phosphatidylinositol cycle, which have been implicated in the
      pathophysiology of affective disorder as well as the action of lithium, and two
      alpha-adrenergic receptors. The present study investigated linkage between manic
      depressive illness and 11 markers from chromosome 20 in two manic depressive
      families, and did not find evidence for a major disease allele. A single
      microsatellite marker, D20S39, yielded positive lod scores or all models in each
      family in the two-point affecteds-only analyses. However, this was not supported
      by two-point analyses with flanking markers or multi-point affecteds-only
      analyses. No evidence of linkage between manic depressive illness and markers
      covering chromosome 20 was found assuming dominant or recessive mode of
      inheritance.

PMID- 8746407
TI  - Identification of two novel polymorphisms and a rare deletion variant in the
      human dopamine D4 receptor gene.
AB  - We report two novel polymorphisms and a rare deletion variant in the human
      dopaine D4 receptor gene. The two polymorphisms are characterized by single base
      pair substitutions, namely a G-->C transversion changing codon 11 from GGG
      (encoding Gly) to CGG (encoding Arg) and a C-->T transition in position -11
      upstream from the start codon. The Arg11 variant occurs at a frequency of about
      1% and the C-->T transition at a frequency of about 7% in German control subjects
      (n = 148). Allele frequencies observed in patients suffering from schizophrenia
      (n = 256) and bipolar affective disorder (n = 99) were similar. The deletion
      variant is characterized by a 21 bp deletion affecting codons 36 to 42 coding for
      amino acids Ala-Ala-Leu-Val-Gly-Gly-Val located in the first transmembrane domain
      of the dopamine D4 receptor. The mutation was identified in a single individual
      suffering from obsessive-compulsive disorder and panic disorder. We were unable
      to detect the deletion in patients with schizophrenia and bipolar affective
      disorder, nor in healthy controls.

PMID- 8746409
TI  - Dopamine D3 receptor gene polymorphism and the psychiatric symptoms seen in first
      break schizophrenic patients.
AB  - To investigate the possible effect of polymorphism at the BalI site of the
      dopamine D3 receptor gene (DRD3) on the phenotype in human subjects, allele and
      genotype frequencies for this polymorphic site were examined in 113 schizophrenic
      patients, including six subgroups, and 48 normal controls. The schizophrenic
      subgroups included patients with early onset, those with a family history, and
      those who suffered from one of the following psychiatric symptoms at their first
      episode: (1) delusion and hallucination; (2) disorganization; (3) bizarre
      behavior; and (4) negative symptoms. No significant differences were observed in
      genotype, allele and homozygosity frequencies between the whole group or any
      subgroup of schizophrenic patients and the controls. The present results indicate
      that polymorphism at the BalI site of the DRD3 is unlikely to be a major
      contributor to any of the psychiatric parameters examined in the present
      population of schizophrenic subjects.

PMID- 8746410
TI  - Suggestive evidence for linkage of schizophrenia to markers on chromosome 13q14.1
      q32.
AB  - Family, twin and adoption studies highlight the influence of genes in the
      aetiology of schizophrenia, though the mode of inheritance is unclear. We have
      been conducting a systematic search for major genes in schizophrenia using a
      series of multiply affected families and report preliminary results of linkage
      under heterogeneity with markers on chromosome 13. A lod2 score of 1.61 for
      marker D13S144 was obtained at theta = 0 and alpha of 0.5 and nearby markers also
      produced positive values.

PMID- 8746411
TI  - Chromosome 22 markers demonstrate transmission disequilibrium with schizophrenia.
AB  - Previously we reported evidence for genetic linkage between markers on chromosome
      22q12 and schizophrenia in 23 multiply affected pedigrees. As part of further
      investigation of this region, we have applied the transmission disequilibrium
      test (TDT) to the genotype data. The TDT is a test for both linkage and linkage
      disequilibrium, and is based on the unequal probability of transmission of two
      different marker alleles from parents to affected offspring. We obtained
      significant results for the marker D22S283 (chi 2 = 35.9, 14 df, p = 0.001),
      D22S278 (chi 2 = 16.5, 6 df, p = 0.01) and F8VWFP (chi 2 = 13.1, 4 df, p = 0.01).
      Application of the Bonferonni correction for testing multiple markers renders the
      results for marker D22S278 and F8VWFP non-significant (from p = 0.01 to p =
      0.14), while the result for D22S283 remains modestly significant at p < 0.02.
      Overall, our findings strengthen the suggestion that the region around D22S283
      contains a susceptibility gene for schizophrenia.

PMID- 8746412
TI  - Prescription of medications that are neither therapeutic nor prophylactic to
      increase productivity.

PMID- 8746413
TI  - An ethicist's commentary on the case of the veterinarian who suspects a local
      cattery of being a source of feline infectious peritonitis.

PMID- 8746414
TI  - Quality assurance and food safety.

PMID- 8746415
TI  - Investigating the relationship between abomasal hairballs and perforating
      abomasal ulcers in unweaned beef calves.
AB  - This study investigated the relationship between abomasal hairballs
      (trichobezoars) and perforating abomasal ulcers in unweaned beef calves <4 mo of
      age. The calves enrolled in the study represented routine necropsy submissions to
      veterinary practitioners in western Canada and to the Western College of
      Veterinary Medicine. Regardless of the cause of death, each calf was examined for
      evidence of abomasal ulcers and hairballs. Thirty-two practitioners and the
      Western College of Veterinary Medicine provided 166 cases for the study; 56 died
      of perforating ulcers (ulcer calves), and 110 died of causes unrelated to
      abomasum (non-ulcer calves). The calves ranged in age from 1-90 d; 154 (92.8%)
      were <61 d of age. Overall, ulcer calves were 2.74 (P = 0.003) times more likely
      to die with an abomasal hairball than were the nonulcer calves. However,
      stratifying the calves into 2 age groups, young (<31 d) and old (>30 d), yielded
      conflicting results. While the young ulcer calves were 3.81 (P = 0.003) times
      more likely to have a hairball than were the young nonulcer calves, there was no
      statistically significant relationship (OR = 0.76, P = 0.65) between ulcer and
      hairballs in the older calves. The authors concluded that the relationship
      between hairballs and ulcers in the young calves was probably spurious, created
      by a Berkson's bias. It is unlikely that abomasal hairballs have a significant
      role in the development of fatal perforating ulcers in beef calves.

PMID- 8746416
TI  - Plasma amylin and insulin concentrations in normoglycemic and hyperglycemic cats.
AB  - The recently discovered pancreatic peptide amylin is postulated to be involved in
      the pathogenesis of feline diabetes mellitus. However, plasma amylin
      concentrations in normal and diabetic cats have not yet been published. The aim
      of the present study was to validate a commercial amylin radioimmunoassay kit for
      the measurement of feline amylin in unextracted plasma, and to measure plasma
      amylin concentrations in normal and diabetic cats. The kit had satisfactory
      specificity, sensitivity, accuracy, and precision, and can be recommended for
      measurement of feline amylin in unextracted EDTA plasma, when nonspecific binding
      of plasma samples is used in the calculation of measured amylin concentration.
      Fasting amylin concentration in cats with normal glucose tolerance was 97 +/- 4
      pmol/L. Plasma amylin increased in parallel with insulin after glucose
      administration in cats with normal and impaired glucose tolerance. In contrast to
      cats with normal glucose tolerance, cats with impaired glucose tolerance had
      markedly delayed amylin and insulin secretion. Diabetic cats had basal
      hypoinsulinemia combined with hyperamylinemia. Hyperamylinemia may lead to
      reduced insulin secretion and insulin resistance, and contribute to the
      development of feline diabetes. In conclusion, feline amylin can be measured in
      unextracted EDTA plasma. Fasting amylin concentrations are approximately 100
      pmol/L, and amylin and insulin are cosecreted in cats with normal and impaired
      glucose tolerance. Increased amylin concentrations may contribute to the
      development of feline diabetes mellitus.

PMID- 8746417
TI  - Spirochete-associated bovine digital dermatitis.

PMID- 8746418
TI  - Bovine spongiform encephalopathy identified in a cow imported to Canada from the
      United Kingdom--a case report.

PMID- 8746419
TI  - Ectopic perianal gland tumor in a timber wolf.

PMID- 8746420
TI  - Neuroaxonal dystrophy in a two-year-old quarter horse filly.

PMID- 8746421
TI  - Hepatic necrosis with toxic copper levels in a two-year-old Dalmation.

PMID- 8746423
TI  - Critical thinking: the case of the skeptical clinician.

PMID- 8746422
TI  - Small animal dentistry in Canada: 1994 survey.
AB  - Small animal dentistry is a rapidly growing area of interest and specialization
      internationally, offering tremendous benefits to patients, clients, and
      practitioners. To date, no studies have been done to determine the standard of
      small animal dental care in Canada. A national mail survey was designed to
      document the prevalence of dental disease in small animal patients, the types of
      veterinary dental procedures being provided by practitioners, as well as home
      care recommendations and compliance for 1994.

PMID- 8746424
TI  - Central nervous system rendez-vous--canine progressive posterior paresis.

PMID- 8746425
TI  - Diagnostic ophthalmology.

PMID- 8746426
TI  - McKeown, Record, and the epidemiology of malformations.
AB  - Thomas McKeown and RG Record were colleagues in Birmingham, England, from 1947 to
      1977. During their first decade together, they laid the foundations of
      epidemiological research on malformations with a series of case-control studies
      of the commoner major defects. They found evidence of numerous trends of birth
      prevalence with variables such as season and year of birth, maternal age, birth
      rank, and socioeconomic status, suggesting that environmental factors played an
      important part in causation. The work that has led recently to the use of folate
      to reduce the risk of neural tube defects is among the lines of research that can
      be traced back to these case-control studies. McKeown and Record also initiated,
      in Birmingham, the first population-based register of malformations to be set up
      as an on-going activity. As well as paving the way for the international networks
      of registers that now exist, the Birmingham register has been used in a variety
      of cohort studies. This work has confirmed many of the case-control study
      findings and continues to yield new observations, including evidence that
      enteroviruses are involved in aetiology.

PMID- 8746427
TI  - Fumes from the spleen.

PMID- 8746428
TI  - Congenital malformations in the vicinity of a smelter in Northern Sweden, 1973
      1990.
AB  - The objective was to evaluate the rates of congenital malformation in children
      born in a population living around a smelter and to employees at the smelter, in
      a community in northern Sweden. By means of record linkage of the birth register
      and various registers of congenital malformations, a retrospective study of a
      birth cohort according to place of parental residence and employment was carried
      out to assess rates of congenital malformation occurring between 1973-1990.
      Neither a general, nor specific, significantly increased risk of congenital
      malformation was seen in the 2724 children born to women living close to the
      smelter or to employees of the smelter compared with the 15191 children in the
      reference population. No increased risk could be ascertained although there are
      reservations concerning the small sample size of the study group.

PMID- 8746429
TI  - Case-control study on maternal residential proximity to high voltage power lines
      and congenital anomalies in France.
AB  - The literature indicates that exposure to electro-magnetic fields (EMF) may
      result in an increased incidence of cancer and spontaneous abortion. The aim of
      the present study was to determine whether living closer to high voltage power
      lines (HVPL) increased the risk of congenital anomalies. We studied residential
      exposure in any municipality in the Central-East Region of France where there was
      at least one residence within 500 metres of a HVPL. This was a matched case
      control design. The cases consisted of all children with congenital anomalies,
      identified to the population-based registry in Central-East France between 1988
      91. We chose two random controls, matched for birth year and municipality, for
      each case. For every case and control, we measured the distance from the HVPL to
      the maternal residence at the time of birth of the child as a surrogate for EMF
      exposure. Using 100 metres from an HVPL as the cut-point between exposure and non
      exposure to electro-magnetic fields produced by HVPL, yielded an odds ratio of
      0.95 (95% (confidence interval) CI: 0.45-2.03). Using 50 metres as the cut-point,
      yielded an OR of 1.25 (95% CI: 0.49-3.22). Among the 11 cases within 100 metres,
      there were 2 children with chromosomal anomalies, but otherwise there was no
      pattern in the occurrence of specific anomalies. These data indicate a lack of
      association between distance to HVPL and the total number of congenital
      anomalies. This study does not have enough statistical power to determine whether
      the prevalence of a specific congenital anomaly is significantly increased as a
      result of living near a HVPL.

PMID- 8746430
TI  - Risk factors for cryptorchidism: a nested case-control study.
AB  - A nested case-control study of cryptorchidism (i.e. undescended testicles) was
      undertaken as part of a hospital-based cohort study of 6699 singleton male
      neonates in New York City. Since some of the cryptorchid infants experienced
      spontaneous descent of their testes, separate analysis was performed for this
      third group of 'late descenders' (n=140). Cases (n=63) represented infants whose
      testes remained undescended at the one year assessment. Controls (n=219)
      represented the next male infant who was delivered immediately after an infant
      who was cryptorchid at birth. The only independent risk factors for
      cryptorchidism were Asian ethnic group (adjusted odds ratio (OR) = 3.90, 95%
      confidence interval (CI) = 1.22-12.41), swollen legs or feet during pregnancy
      (adjusted OR = 2.16, 95% CI = 1.15-4.04), a family history of cryptorchidism
      (adjusted OR = 4.32, 95% CI = 1.91-9.80), low birthweight (adjusted OR = 4.10,
      95% CI = 1.39-12.08), and use of analgesics during pregnancy (adjusted OR = 1.93,
      95% CI = 1.03-3.62). Multiple logistic regression analysis was also performed to
      identify those factors that were associated with late testicular descent. In this
      analysis the independent risk factors were black or Hispanic ethnicity (adjusted
      OR = 2.05, 95% CI = 1.09-3.83), a family history of cryptorchidism (adjusted OR =
      4.25, 95% CI = 1.84-9.78), consumption of cola-containing drinks during the
      pregnancy (adjusted OR = 2.09, 95% CI = 1.10-3.99), a low birthweight delivery
      (adjusted OR = 9.78, 95% CI = 3.39-28.20), and preterm birth (adjusted OR = 4.01,
      95% CI = 1.66-9.70).

PMID- 8746431
TI  - Congenital malformations in newborns of women with established and gestational
      diabetes in Washington State, 1984-91.
AB  - We examined the relationship between diabetes in pregnancy and the development of
      congenital malformations, in a population-based retrospective study using birth
      certificate data for all liveborn children delivered from 1984 until 1991 in
      Washington State. Births to mothers with established and gestational diabetes
      numbered 1511 and 8869 respectively. For comparison we selected 8934 births to
      mothers without diabetes. The prevalence of congenital malformations in neonates
      was 7.2%, 2.8% and 2.1% among mothers with established diabetes, gestational
      diabetes, and without diabetes, respectively. Newborns of mothers with
      established diabetes were more likely to have a congenital malformation than
      newborns of non-diabetic mothers (prevalence odds ratio = 4.0; 95% confidence
      interval 3.1-5.1). In contrast, there was only a slightly higher prevalence of
      congenital malformations among newborns of mothers with gestational diabetes
      (prevalence odds ratio = 1.3; 95% CI 1.0-1.6). The association with maternal
      established diabetes was greater for neonates with multiple malformations (7.8;
      95% CI 3.3-18.1) than for single malformations (2.9-95% CI 2.1-3.9). Four to
      seven fold associations were observed with skeletal, cleft lip/palate, neural
      tube and heart abnormalities. The association of established diabetes with
      congenital malformations was nearly twice as strong among female neonates
      (prevalence odds ratio = 5.4; 95% CI 3.7-8.0) than among male neonates
      (prevalence odds ratio = 3.1; 95% CI 2.2-4.5). No such variation was observed for
      associations with gestational diabetes. This study enlarges on previous work
      relating congenital anomalies to established diabetes and supports the
      possibility of a weak association with gestational diabetes.

PMID- 8746432
TI  - The risk of diabetes in a subsequent pregnancy associated with prior history of
      gestational diabetes or macrosomic infant.
AB  - Prior studies suggest that diagnosis of gestational diabetes is associated with
      increased risk for development of gestational diabetes in future pregnancies, and
      with subsequent onset of established diabetes. The magnitudes of these risks have
      not been measured. Using linked birth certificate data from Washington State it
      is possible to identify all women with two or more births occurring during 1984
      91. All women with gestational diabetes (n=1375) or with established diabetes
      (n=220), during their pregnancy for the second or greater birth were identified,
      and a control group consisting of women whose second or greater birth was not
      complicated by either condition was randomly selected (n=6380). Data from the
      birth certificate, for the previous birth, were compared in order to estimate the
      risks of developing gestational or established diabetes in a subsequent pregnancy
      among women with prior gestational diabetes relative to women without gestational
      diabetes. The age-adjusted risk of developing gestational diabetes in the
      pregnancy for the subsequent birth associated with prior gestational diabetes was
      23.2 (95% (confidence interval) CI = 17.2-31.2); the risk of having developed
      established diabetes by the time of the subsequent birth was 55.5 (95% CI = 34.4
      89.4). Women who had a macrosomic infant (>4000 gm) in the prior birth were also
      at increased risk for developing gestational diabetes (odds ratio OR = 3.3, 95%
      CI = 2.9-3.8) or established diabetes (OR = 5.8, 95% CI = 4.0-8.5). When data
      were restricted to patients with only one prior birth, to patients with early
      prenatal care, to delivery at facilities with long-established protocols for
      diagnosing gestational diabetes, or to more recent years, the risk estimates
      remained similarly elevated. The 23-fold increased risk of gestational diabetes
      associated with having gestational diabetes indicated on the birth certificate of
      a woman's previous baby, although not unexpected, is still remarkable and
      reinforces the importance of careful monitoring of women with this history.
      Although changes in how screening is conducted may account for some of the
      elevation in risk, our results stayed consistently elevated even when
      restrictions were made within the data to control for this. The fact that there
      was a 56-fold increased risk of having developed established diabetes by the time
      of the subsequent birth on record, associated with prior gestational diabetes,
      and a 6-fold increased risk associated with a macrosomic infant, supports the
      idea that these may be early steps in the development of established diabetes,
      and identifies a group that may benefit from close monitoring and possible
      intervention.

PMID- 8746433
TI  - Incidence of childhood cancer in Thailand 1988-1991.
AB  - Incidence rates of cancers of childhood in Thailand are presented for the first
      time, and compared with results from cancer registries in Asia, Europe and the
      USA. As elsewhere in the world, leukaemia (principally acute lymphocytic), brain
      tumours and lymphomas comprise two-thirds of all childhood neoplasms. Carcinomas
      are rare, but the principal sites (liver, nasopharynx, thyroid and salivary
      gland) are extremely unusual elsewhere. Several features of the cancer pattern
      correspond to that in other Asian populations (China, Japan, Philippines), in
      particular the low incidence of Hodgkin's disease, Wilms' tumour and Ewing's
      sarcoma. Conversely, Burkitt's lymphoma is more common than elsewhere, although
      this may represent increasing awareness of this diagnosis amongst clinicians in
      recent years.

PMID- 8746434
TI  - Demographic survey of the level and determinants of perinatal mortality in
      Karachi, Pakistan.
AB  - A demographic survey was used to estimate the level and determinants of perinatal
      mortality in eight lower socio-economic squatter settlements of Karachi,
      Pakistan. The perinatal mortality rate was 54.1 per 1000 births, with a
      stillbirth to early neonatal mortality ratio of 1:1. About 65% of neonatal deaths
      occurred in the early neonatal period, and early neonatal mortality contributed
      32% of all infant deaths. Risk factor assessment was conducted on 375 perinatal
      deaths and 6070 current survivors. Poorer socio-economic status variables such as
      maternal and paternal illiteracy, maternal work outside the home and fewer
      household assets were significantly associated with perinatal mortality as were
      biological factors of higher parental age, short birth intervals and poor
      obstetric history. Multivariable logistic analysis indicated that some socio
      economic factors retained their significance after adjusting for the more
      proximate biological factors. Population attributable risk estimates suggest that
      public health measures for screening of high-risk women and use of family
      planning to space births will not improve perinatal mortality substantially
      without improvement of socio-economic conditions, particularly maternal
      education. The results of this study indicate that an evaluation of perinatal
      mortality can be conducted using pregnancy histories derived from demographic
      surveys.

PMID- 8746435
TI  - A review of perinatal autopsy rates worldwide, 1960s to 1990s.
AB  - Epidemiological data derived from death certification in the absence of a
      necropsy can be erroneous. Despite concern over adult hospital necropsy rates,
      which have fallen dramatically in the last 40 years, relatively less has been
      published regarding perinatal necropsy rates. A literature review of necropsy
      rates for neonatal deaths, stillbirths and perinatal losses was undertaken. There
      is a wide variation in the perinatal necropsy rates worldwide but the numbers
      appear to be higher than adult hospital rates. The necropsy rate for neonatal
      deaths appears to be lower than that for stillbirths. It is hoped that the review
      will serve to alert readers to remain vigilant against any fall in the perinatal
      necropsy rates.

PMID- 8746436
TI  - Parental choice and neonatal resuscitation.

PMID- 8746437
TI  - Multiple antioxidants protect against heme protein and lipid oxidation in kidney
      tissue.
AB  - The effect of antioxidant nutrients in rat kidney homogenates was studied by
      measuring the formation of oxidized heme proteins (OHP) and thiobarbituric acid
      reactive substances (TBARS) during spontaneous oxidation at 37 degrees. OHP were
      analyzed using a modified spreadsheet protocol; the Heme Protein Spectra Analysis
      Program (HPSAP). Male Sprague-Dawley (SD) rats were fed a basal diet fortified
      with vitamin E, selenium, or beta-carotene, or a combination of all three
      antioxidants. A second group of male SD rats received a basal diet fortified with
      Trolox, ascorbic acid palmitate, acetylcysteine, beta-carotene, coenzyme Q10,
      coenzyme Q0, and (+)-catechin. A control group of rats was given a vitamin E- and
      selenium-deficient basal diet. The amount of TBARS production during a 1 h
      reaction decreased as the relative antioxidant effectiveness of the dietary
      treatments increased. Dietary treatments providing nine antioxidants
      significantly reduced the formation of OHP and methemoglobin during the 1 h
      reaction compared to the dietary treatment providing only two antioxidant
      nutrients. These data suggest that increasing the diversity and quantity of
      antioxidants in the diet provides significantly more protection for heme proteins
      and lipids in kidney tissue than individual antioxidants or a combination of
      vitamin E and selenium.

PMID- 8746438
TI  - Oxidative stress in acidic conditions increases the production of inositol
      phosphates in chick retinal cells in culture.
AB  - The effect of oxidative stress on the production of [3H]inositol phosphates
      (InsP) by retinal cells in culture was analyzed. The process of oxidation was
      induced by incubating the cells with ascorbic acid and ferrous sulphate, and
      increased extent of oxidation was obtained by varying the pH from neutral to
      moderate acidosis (pH 6.5). The oxidative process significantly reduced cell
      viability (about 15%) by decreasing the capacity of mitochondria dehydrogenases
      to reduce tetrazolium salts, but had no effect on the leakage of lactate
      dehydrogenase. The production of [3H]InsP, in the absence of receptor activation,
      was increased dose dependently by oxidative stress. Maximal increases to 189 +/-
      7%, 197 +/- 13%, and 329 +/- 22% were observed, respectively, for inositol
      monophosphates (InsP1), inositol bisphosphates (InsP2), and inositol
      trisphosphates (InsP3), at 2.5 nmol thiobarbituric acid reactive substances
      (TBARS)/mg protein. The response to cholinergic receptor activation was slightly
      decreased in cells oxidized in acidic conditions. Antagonists of glutamate
      receptors failed to inhibit the enhancement in InsP that occurred upon cellular
      oxidation, suggesting that the effect was not mediated by activation of glutamate
      receptors. Cellular oxidation increased by about two fold the uptake of 45Ca2+ in
      the absence of agonist stimulation. However, stimulation of phospholipase C by
      Ca2+ did not mediate the increase in [3H]InsP upon cell oxidation in acidic
      conditions, because the addition of 1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien
      17-yl]amino] hexyl]-1-H-pyrrole-2,5-dione (U-73122), an inhibitor of
      phospholipase C-dependent processes, did not affect the production of [3H]InsP in
      oxidized cells. Nevertheless, U-73122 significantly inhibited carbachol- and K(+)
      stimulated accumulation of [3H]InsP. Furthermore, the enhancement of [3H]InsP
      induced by ascorbate/Fe2+ was still observed in the absence of external Ca2+.
      This increase in the production of InsP did not substantially induce the release
      of Ca2+ from internal stores. The results suggest that both Ca(2+)-dependent and
      Ca(2+)-independent pathways are involved in oxidative stress-mediated InsP
      increment, and that the enzymes of the InsP metabolism may be affected by
      oxidation.

PMID- 8746439
TI  - Neutrophil-induced lung damage after hepatic ischemia and endotoxemia.
AB  - Administration of Salmonella enteritidis endotoxin (0.5 mg ET/kg) during
      reperfusion (RP) after short-term hepatic ischemia (20 min) caused severe liver
      injury induced by Kupffer cells and neutrophils and a high mortality rate. To
      investigate potential lung damage in this model, lung wet-to-dry weight ratios
      (W/D) and broncho-alveolar lavage (BAL) protein content were determined after 4 h
      of reperfusion. Both parameters increased significantly during RP/ET (W/D: 4.4 +/
      0.1; BAL: 639 +/- 30 micrograms/ml) compared to controls (W/D: 3.5 +/- 0.1; BAL:
      332 +/- 17). The antioxidants Trolox or tirilazad mesylate (U-74006F) effectively
      reduced the BAL protein increase. Alveolar macrophages were not activated;
      however, neutrophils isolated from the lung microvasculature of RP/ET animals
      showed a 300% increase of spontaneous and PMA-induced superoxide formation
      compared to controls (spontaneous: 1.4 +/- 0.5 nmol O2-/h/10(6) cells; PMA: 2.2
      +/- 0.4). Complement factors and TNF-alpha injection induced a similar priming of
      vascular neutrophils for superoxide generation. Vascular neutrophil activation
      highly correlated with the severity of lung injury. It is concluded that
      neutrophils accumulated in the lung microvasculature were the major source of the
      oxidant stress and mainly responsible for lung injury under these conditions.
      Antioxidants such as tirilazad mesylate (U-74006F) may have therapeutic potential
      for attenuating lung injury induced by remote organ trauma and a systemic
      inflammatory response.

PMID- 8746440
TI  - ESR spin trapping investigation of radical formation from the reaction between
      hematin and tert-Butyl hydroperoxide.
AB  - Various mechanisms have been proposed for the reaction between heme proteins and
      organic hydroperoxides, including a peroxidase-type mechanism and homolytic
      cleavage. We used electron spin resonance (ESR) spectroscopy to investigate the
      formation of radicals in a hematin/tert-butyl hydroperoxide system. Spin trapping
      studies, using 5,5-dimethyl-1-pyrroline N-oxide (DMPO), showed the formation of
      peroxyl and alkoxyl radicals in this system. At higher hematin concentrations an
      alkyl radical adduct could also be detected, which was identified as the methyl
      radical by using the spin trap 2-methyl-2-nitrosopropane. Furthermore, the
      relative contribution of the peroxyl and alkoxyl radical adducts was determined
      at various DMPO concentrations using computer simulation. It was found that at
      low DMPO concentrations both the alkoxyl and the peroxyl radical adducts could be
      detected. At higher DMPO concentrations, on the other hand, the alkoxyl radical
      dominated, whereas the peroxyl radical adduct decreased to a small portion of the
      total radical adduct population. Thus, the alkoxyl radical was the initial
      radical, produced by homolytic scission of the O-O bond of the hydroperoxide by
      ferric hematin. Although some tert-butyl peroxyl radicals could be detected by
      direct ESR, the majority of the peroxyl radicals detected by spin trapping were
      methyl peroxyl radicals, formed in the reaction between methyl radicals (formed
      by beta-scission of the alkoxyl radicals) and oxygen.

PMID- 8746441
TI  - Conditions allowing redox-cycling ubisemiquinone in mitochondria to establish a
      direct redox couple with molecular oxygen.
AB  - The present investigation seeks to elucidate the molecular mechanism responsible
      of the transformation of redox-cycling ubiquinone (UQ) from a save electron
      carrier to an O2.- generator as observed in toluene-treated mitochondria as well
      as in mitochondria exposed to conditions of organ ischemia/reperfusion. Starting
      from the earlier finding that for thermodynamic grounds autoxidation of
      ubisemiquinone (SQ.-) requires the accessibility of protons, two possibilities
      were considered: a) protons from the aqueous phase may penetrate into the
      phospholipid bilayer and react with SQ.- due to a decreased hydrophobicity of the
      membrane, b) the physical state of the membrane remains unchanged while the
      binding of redox-cycling UQ is changed such that SQ.- will come into contact with
      the aqueous phase in the polar head group section. Spin probes were used to
      follow changes of the physical order of phospholipids of the inner mitochondrial
      membrane. Binding changes of mitochondrial SQ.- were assessed from power
      saturation experiments and spin-spin interactions with a Cr3+ salt of the aqueous
      phase were studied to recognize orientation changes via the polar head group
      section of the membrane. Our results show that autoxidation of SQ.- occurs in two
      different ways. In the case of membrane insertion of toluene, the physical
      property of the membrane was affected such that protons could penetrate and allow
      SQ.- to undergo autoxidation. In contrast, mitochondrial respiration of cytosolic
      NADH accumulating during ischemia involves a low saturating SQ.- species that
      readily autoxidizes due to its spatial orientation close to the aqueous face of
      the membrane. We conclude from these observations that in line with
      thermodynamics autoxidation of SQ.- in mitochondria requires protons that
      normally have no access.

PMID- 8746442
TI  - 4-hydroxynonenal inhibits Na(+)-K(+)-ATPase.
AB  - 4-Hydroxynonenal binds rapidly to Na(+)-K(+)-ATPase, and this was accompanied by
      a decrease in measurable sulfhydryl groups and a loss of enzyme activity. The I50
      value for Na(+)-K(+)-ATPase inhibition by 4-hydroxynonenal was found to be 120
      microM. Although the sulfhydryl groups could be completely restored with beta
      mercaptoethanol during the reaction of the Na(+)-K(+)-ATPase-HNE-adduct, the
      Na(+)-K(+)-ATPase activity was only partially restored by this reducing agent. A
      combination of hydroxylamine and beta-mercaptoethanol yielded the greatest
      recovery of enzyme activity, 85% of original. Thus, 4-hydroxynonenal binding to
      Na(+)-K(+)-ATPase led to an irreversible decrease of enzyme activity under the
      conditions employed. It is hypothesized that 4-hydroxynonenal reacts with
      sulfhydryls at sites on the enzyme that are inaccessible by beta-mercaptoethanol.
      Furthermore, evidence was obtained that 4-hydroxynonenal reacts with other amino
      acids such as lysine to form adducts that also interfere with protein function.

PMID- 8746443
TI  - Factors affecting DNA damage caused by lipid hydroperoxides and aldehydes.
AB  - Single (SSB) and double strand breaks (DSB) in supercoiled plasmid DNA pBR322
      reacted with linoleic acid hydroperoxides (LOOH) were followed by agarose gel
      electrophoresis to obtain definitive information about factors affecting LOOH
      interaction with DNA. In water, LOOH induced extensive DSB, which were metal
      mediated and increased with incubation time. Adventitious metal bound to DNA was
      sufficient to decompose LOOH to reactive radicals, activity that was not readily
      inhibited by chelators DTPA and desferrioxamine. Added Fe2+ and Fe3+ increased
      SSB and DSB, although the effects of Fe2+ were more extensive. Above 100 microM
      both valences inhibited DNA damage. Strand breakage by LOOH proceeded via lipid
      alkoxyl and peroxyl radicals. Aldehydic lipid peroxidation products induced
      strand breaks via oxidation of double bonds, not by reactions of the carbonyl
      groups. Lipophilic antioxidants BHA, BHT, and alpha-tocopherol were about 20
      times more effective than hydrophilic free radical scavengers sodium benzoate,
      inositol, DMSO, and mannitol in preventing LOOH-induced strand breaks, supporting
      lipid phase localization of the damage.

PMID- 8746444
TI  - Marchantins and related polyphenols from liverwort: physico-chemical studies of
      their radical-scavenging properties.
AB  - Structurally unique macrocyclic phenols from liverwort, i.e., marchantins and
      related substances, were studied for their antioxidative potential using pulse
      radiolytic and EPR-spectroscopic techniques. The generally diffusion-controlled
      rate constants for scavenging of azide radicals as a model electrophilic species
      and the sufficiently slow bimolecular decay confirm their antioxidative
      potential. Transient spectra after pulse radiolysis and the EPR spectra both
      demonstrate the internal strain of the macrocyclic ring. One compound,
      Perrottetin D, furthermore gave proof to the hitherto only kinetically verifyable
      superior radical-scavenging capability of the aroxyl radical derived from a
      phenolic antioxidant.

PMID- 8746445
TI  - In vivo evidence of hydroxyl radical formation induced by elevation of
      extracellular glutamate after cerebral ischemia in the cortex of anesthetized
      rats.
AB  - The in vivo interrelation between excitotoxicity and oxidative stress following
      cerebral ischemia in the cortex of anesthetized rats was investigated. Cerebral
      ischemia was induced by ligation of the bilateral common carotid arteries and the
      unilateral middle cerebral artery. Microdialysis perfusion with on-line high
      performance liquid chromatography was used to monitor the hydroxyl radical
      levels. Extracellular hydroxyl radical levels were quantitated as the increased
      formation of 2.3 and 2.5 dihydroxybenzoic acid (DHBA), the hydroxylative products
      of salicylic acid contained in the microdialysis perfusion solutions. Elevated
      cortex extracellular glutamate content, resulting from the cerebral ischemia,
      caused an increase in the formation of hydroxyl radicals. Exogenous perfusion of
      authentic glutamate solutions through implanted microdialysis probes also
      resulted in increased hydroxyl radical formation in the cortex. The 2.3 and 2.5
      DHBA levels remained elevated for an entire 80-min ischemic period. These results
      suggest that, after cerebral ischemia, increased oxidative stress did occur in
      anesthetized rats, and the oxidative stress may result from increased
      excitotoxicity.

PMID- 8746446
TI  - Improved analysis of malondialdehyde in human body fluids.
AB  - The widely used TBA assay for lipid peroxidation was modified to minimize
      artefactual oxidative degradation of lipids during the assay. Formation of the
      TBA-MDA condensation product was studied with and without exclusion of oxygen,
      and the concentration effect of BHT addition was examined. Oxygen was depleted
      from the reaction mixture by extensive argon gassing. Exclusion of oxygen
      resulted in decreased TBARS production in plasma but not in standard solutions.
      High BHT concentrations resulted in a similar effect. At concentrations higher
      than 3 mmol/l BHT exclusion of oxygen had no additional effect. By measuring n
      butanol extracts in a multititer plate reader this modified method was made
      suitable as a preliminary screening assay of human body fluids for lipid
      peroxidation.

PMID- 8746447
TI  - Onset of expression of the alpha subunit of Ca2+/calmodulin-dependent protein
      kinase II and a novel related protein in the developing retina.
AB  - Calcium-calmodulin-dependent protein kinase II is an abundant protein in the
      nervous system and has been associated with many aspects of neuronal function,
      including events related to synaptic transmission. The purpose of this study is
      to correlate the onset of expression of this kinase with a specific developmental
      event in retinal morphogenesis using a monoclonal antibody to the 50-kDa alpha
      subunit. Microscopy showed the antigen to be associated with the plexiform layers
      of the retina. Western blots demonstrated that the onset of expression of the
      alpha-subunit coincided in time with the initial formation of the plexiform
      layers. However, the onset of expression of the 50-kDa alpha-subunit was preceded
      by the earlier embryonic appearance of a related 82.5-kDa antigen that was
      recognized by the antibody. The amount of this latter protein declined as the
      amount of the alpha-subunit increased in retinal homogenates. Although this
      related 82.5 kDa protein disappeared from blots of retinal homogenates after
      embryonic d 14, it could be detected in concentrated supernatant fractions
      isolated from the retinae of hatched chicks. Microscopy showed that a subset of
      retinal cells and their processes contained this antigen in early embryonic
      chicks. Finally, the 50 kDa alpha-subunit of kinase II and the 82.5 kDa novel
      antigen were shown to be separable by differential centrifugation.

PMID- 8746448
TI  - Insulin-induced differentiation and modulation of neuronal thread protein
      expression in primitive neuroectodermal tumor cells is linked to phosphorylation
      of insulin receptor substrate-1.
AB  - Neuronal thread proteins (NTPs) are a family of developmentally regulated
      molecules expressed in central nervous system (CNS) neurons and primitive
      neuroectodermal tumor (PNET) cell lines. NTP gene expression is modulated with
      DNA synthesis, neuritic sprouting, and neuronal differentiation. The present
      study explores the mechanism of insulin modulation of NTP gene expression during
      neuronal differentiation using PNET cell lines of CNS origin. PNET2 cells
      underwent neuronal differentiation with neurite outgrowth coupled with transient
      up-regulation of several species of NTP. In contrast, PNET1 cells failed to
      differentiate in response to insulin stimulation, although insulin receptors were
      more abundant than in PNET2 cells. Analysis of the insulin-mediated signal
      transduction pathway demonstrated that the lack of insulin responsiveness in
      PNET1 cells was primarily caused by impaired insulin-mediated tyrosyl
      phosphorylation of the insulin receptor substrate-1 (IRS-1). Correspondingly, the
      association between phosphatidyl-inositol 3 (PI3) kinase and phosphorylated IRS-1
      was reduced in PNET1 compared with PNET2 cells. In contrast, the levels of IRS-1
      protein were similar in PNET1 and PNET2 cells, and expression of the insulin
      receptor beta subunit (Ir beta) and insulin-mediated tyrosyl phosphorylation of
      the Ir beta were greater in PNET1 than PNET2 cells. The findings suggest that
      insulin effected neuronal differentiation and modulation of NTP gene expression
      in PNET cells utilizes a signal transduction cascade that requires tyrosyl
      phosphorylation of IRS-1.

PMID- 8746449
TI  - Cloning and promoter analysis of the human B-50/GAP-43 gene.
AB  - We here report isolation of exon 1 and analysis of the human B-50 promoter. A
      human genomic lambda EMBL3 library was screened with a homologous PCR probe. Two
      independent clones were analyzed and partially sequenced: They contained up to 5
      kb sequence upstream of the translation start site and approx 13 kb of intron 1
      sequence. There was a high degree of homology between the rat and the human gene
      with 100% homology from -504 to -427, with respect to the translation start
      codon. However, relatively long GT and GA repeats as seen in the rat gene were
      absent. Various promoter-reporter constructs, containing 5.0 to 0.12 kb of the
      upstream region, were transfected into undifferentiated and neuroectodermally
      differentiated P19-EC. Two promoter activities were found. The minimal fragment
      with promoter activity still responsive to differentiation was the 0.22 kb
      construct, similar to rat promoter P2. We conclude that the human B-50 gene is
      expressed in a similar way to the rat B-50 gene, based on the presence of two
      transcripts, the high degree of homology between the rat and the human sequence,
      and the two promoter activities found in P19-EC cells.

PMID- 8746450
TI  - Decreased incorporation of D-glucosamine into glycosphingolipids of intact
      Familial Dysautonomia lymphoblasts.
AB  - Familial Dysautonomia (FD) is an autosomal recessive Ashkenazi Jewish genetic
      disease, of unknown etiology, involving deficits in both autonomic and sensory
      functions. Previously, we found statistically significant increases in
      globotriaosylceramide (Gb3) in FD fibroblasts and lymphoblasts, and a decrease in
      ganglioside levels. FD fibroblasts exhibited pleiomorphic changes at the light
      microscopy level, suggestive of changes in the plasma membrane. We described an
      increase in Gb3 on the surface of synchronized cells at the G1/S boundary of the
      cell cycle, based on Gb3-verotoxin (derived from E. coli) interactions. Using D
      glucosamine-1-14C as an in vitro precursor, we herein report a marked decrease in
      the rate of incorporation of D-glucosamine into the sialic acid and the N
      acetylgalacto/glucosamine moieties of gangliosides and neutral glycosphingolipids
      in intact FD compared to control lymphoblasts. The total ganglioside content of
      FD cells (primarily GM3, measured as incorporation of 3H from NaB3H4) was also
      decreased. These data indicate differences in the turnover of sialic acid and N
      acetylated sugar constituents in FD vs normal cells.

PMID- 8746451
TI  - Activation of a reporter gene responsive to NGFI-B in cultured neurons and
      astrocytes.
AB  - NGFI-B is an immediate early gene and orphan member of the nuclear receptor
      superfamily. It is induced in several tissues, including brain, and in cultured
      cerebellar granule cells in response to different stimuli. Since both the
      induction of its mRNA as well as the level and function of its gene product are
      under the control of the inducing stimulus, we wanted to study the final outcome
      of the stimulus, i.e., transcriptional activity, by means of a specific,
      artificial reporter gene in cultured CNS cells. Cultured cerebellar granule cells
      and astrocytes were transfected with an NGFI-B responsive reporter gene to study
      the role of NGFI-B as a transcriptional activator after stimulation of the
      protein kinase A and C pathways. In both cell types, stimulation of either
      protein kinase A or C with forskolin (10 microM) or phorbol 12-myristate 13
      acetate (0.1 microM), respectively, gave up to fivefold induction of the reporter
      gene. In the granule cells a combined treatment gave a strong synergistic
      induction of the reporter gene. The astrocytes showed only weak synergy,
      indicating cell-specific regulation of the target gene by the two kinases.

PMID- 8746452
TI  - Hypomethylation of the amyloid precursor protein gene in the brain of an
      Alzheimer's disease patient.
AB  - Aberrant expression of the amyloid precursor protein (APP) gene may contribute to
      the beta-amyloid deposition seen in Alzheimer's disease and Down syndrome
      patients. Genomic DNA was isolated from human brain tissue and digested with
      HpaII, an enzyme sensitive to CpG methylation. Southern-blot analysis revealed
      the absence of methylation at a site in the APP gene of an Alzheimer's disease
      subject. This site was methylated in a nondemented subject and a subject with a
      non-Alzheimer's type of dementia (Pick's disease). This is the first report of an
      epigenetic defect in an Alzheimer's disease patient and the observation suggests
      that hypomethylation of the APP gene may be one of several factors contributing
      to aberrant gene expression in Alzheimer's disease.

PMID- 8746454
TI  - Compendium of food additive specifications. Addendum 3. Joint FAO/WHO Expert
      Committee on Food Additives 44th session.

PMID- 8746453
TI  - Residues of some veterinary drugs in animals and foods. Monographs prepared by
      the forty-third meeting of the Joint FAO/WHO Expert Committee on Food Additives.

PMID- 8746455
TI  - Sequence and gene content in 52 kb including and centromeric to the G6PD gene in
      Xq28.
AB  - A cosmid containing 36.4 kb of high GC human DNA centromeric to the G6PD gene has
      been analyzed. The sequence was 99.9% precise, based on the comparison of 4.3 kb
      that overlaps an earlier analysis of 20.1 kb containing G6PD. Properties of the
      entire 52 kb region that may be characteristic of high GC portions of the genome
      include a very high density of sixty-two half or full Alu sequences, or 1.2/kb,
      and an absence of L1 sequences. Other highly repetitive sequences include 11 MER
      sequences, one of them interrupted at two positions by groups of 3 Alu elements.
      In segments of unique sequence, computer-aided analysis predicted three possible
      genes, one of which has thus far been confirmed by the recovery of a
      corresponding cDNA, both by a direct hybridization method and by a PCR-based
      method based on a primer pair inferred from the genomic sequence. The cDNA has
      been sequenced, and is completely concordant with counterpart genomic sequence;
      it has no resemblance to any previously described gene.

PMID- 8746456
TI  - Mapping of transcribed sequences on human chromosome 19.
AB  - 30 EST/STS have been mapped on human chromosome 19 using a highly specific hncDNA
      library as a source of transcribed sequences. In addition more than 50 sites
      constituting 19 families of closely related sequences containing at least one
      transcribed member each were mapped across the chromosome. Chromosome-19 specific
      hncDNA clones were hybridized to chromosome 19 cosmids that were previously
      assembled into contigs covering about 80% of Chr19. The hybridization results
      were verified by PCR. Such an approach to EST mapping provides information on
      possible locations of genes as transcribed units of genome and on location of
      repeated elements used for the priming the hncDNA synthesis. Mapped hncDNA
      sequences may serve as good starting points for the systematic sequencing of
      transcribed genomic regions.

PMID- 8746457
TI  - DNA polymorphism detection in Tribolium castaneum (HERBST) (Coleoptera:
      Tenebrionidae): potential use in stored product pest management.
AB  - Different pairs of oligonucleotide primers have used for the detection of DNA
      polymorphism between Tribolium castaneum strains. Amplification of a major DNA
      fragment and two minor was observed in all strains tested excepted for one strain
      from France which present only two major bands (respectively at 800 bp and 880
      bp). Arbitrarily, the major band amplified from a DNA sample of the strain
      originating from the Philippines was choosen as a probe (sequence of 487 bp in
      length). The combination of this probe and restriction enzymes permitted the
      discrimination between strains. Our results show that RAP marker of Tribolium
      castaneum could be used to study its population genetics.

PMID- 8746458
TI  - Cloning and sequencing of the streptokinase gene from streptococcus pyogenes (CIP
      56.57).
AB  - The streptokinase gene of the Streptococcus pyogenes strain CIP 56.57 was cloned
      and sequenced. This sequence coding for a 441 amino acid protein is well
      conserved among streptococcus species: there are two very conserved domains
      separated by a more variable region.

PMID- 8746459
TI  - Rab2 nucleotide coding sequence in gallus gallus and it phylogenetic position.
AB  - The nucleic acid sequence of the chicken rab2 mRNA was determined by sequencing a
      full length cDNA. The phylogeny of rab2 sequences was established.

PMID- 8746460
TI  - Structure of histone H2B and H4 genes of the sea cucumber Holothuria tubulosa.
AB  - A genomic library of the sea cucumber Holothuria tubulosa was screened with human
      and murine histone gene hybridization probes. A recombinant phage carrying an H4
      gene was isolated and sequenced. Hybridization analysis of the entire 20 kb phage
      insert with probes for H1, H2A, H2B and H3 histones was negative except for H2B.
      This solitary arrangement of the two neighbouring histone H4 and H2B genes is in
      contrast to the organization of 'cleavage stage' histone genes, which are
      arranged in tandem quintets of genes encoding the 5 histone classes. Gene
      organization and sequence features indicate that the two Holothuria genes are the
      equivalents of a known pair of late H2B and H4 genes which have been described in
      the genome of sea urchins. This result shows that the simultaneous occurrence of
      tandem repeats of histone gene quintets and smaller groups of structurally
      distinct histone gene subtypes is not unique for sea urchins, but also applies to
      other echinodermata, such as the sea cucumber Holothuria tubulosa.

PMID- 8746461
TI  - Nucleotide sequence of the haemagglutinin-neuraminidase (HN) gene of a Malaysian
      heat resistant viscerotropic-velogenic Newcastle disease virus (NDV) strain
      AF2240.
AB  - The nucleotide sequence of the haemagglutinin-neuraminidase (HN) gene of
      Newcastle disease virus (NDV) viscerotropic-velogenic strain AF2240 was
      determined by direct RNA sequencing and by sequencing RT-PCR products. It encodes
      a single open reading frame of 581 amino acids with a calculated Mr of 63.8 kDa.
      The predicted sequence contains five asparagine glycosylation sites. Comparison
      of the AF2240 HN protein sequence with 13 other previously published sequences
      showed 88% homology. This HN protein is unique because it lacked the Arg 403
      residue which is present in all of the other strains and cannot be grouped under
      the proposed three size classes of HN proteins in NDV.

PMID- 8746462
TI  - Nucleotide sequence of the variable region of the heavy and light chains of a
      monoclonal IgG antibody reactive to herbicides, terbutryn and prometryn.
AB  - Members of the triazine family of herbicides are reliable indicators of
      contamination of the ground water or soil with pesticide residues. To facilitate
      better detection of the chemical residues using improved immunoassay procedures,
      several monoclonal antibodies against triazine herbicides have been developed.
      K1F4 is a hybridoma secreting monoclonal (IgG) antibody reactive to terbutryn and
      prometryn, two members of the triazine family. We have cloned the genes encoding
      the variable regions of the heavy and light chains of this monoclonal antibody
      and report the nucleotide sequence here.

PMID- 8746463
TI  - Identification of a glutathione peroxidase homolog in Neisseria meningitidis.
AB  - Glutathione peroxidase is an antioxidant enzyme found in a diverse array of
      eukaryotic species. We have determined the DNA sequence of a glutathione
      peroxidase homolog in the pathogenic bacterium Neisseria meningitidis. The
      sequence displays features of a functional gene, but lacks a selenocysteine
      encoding in-frame TGA codon characteristic of most mammalian glutathione
      peroxidase genes. The derived amino acid sequence encoded by the N. meningitidis
      homolog predicts a 19.9 kDa protein that displays a high level of amino acid
      identity with other gluathione peroxidase sequences, particularly within four
      conserved regions of the enzyme.

PMID- 8746464
TI  - Nucleotide sequence of exons 5 to 9 of the p53 tumour-suppressor gene of the
      donkey (Equus asinus).
AB  - The evolutionary conserved region of the equine homologue of the p53 gene from
      the donkey genome was PCR amplified and cloned. The 1380 bp fragment consisted of
      exons 5 to 9 and the intervening introns. The exonic and intronic DNA sequences
      showed a variable but high level of homology with previously published human
      sequences. The aminoacid sequences corresponding to the evolutionary conserved
      domains II, III, and V were identical to the human regions, whilst domain IV was
      96% homologous.

PMID- 8746465
TI  - Surgical advances. A comprehensive approach to surgical rejuvenation of the eyes.
AB  - Methods to rejuvenate the eye region include shortening of the forehead, raising
      the brow, improving the upper eyelids by excision of blepharochalasis tissue, and
      reducing lower eyelid fat pads by a transconjunctival approach and at the same
      time elevating the stretched lateral canthus by an effective canthopexy. The
      risks and complications of these procedures are minimal, circumscribing the
      shortcomings of conventional blepharoplasty.

PMID- 8746466
TI  - Less is more: a conservative approach to male rhinoplasty.
AB  - Rhinoplasty in men has caused more traumatic problems of dissatisfaction, as
      compared to women, ranging from higher rates of complaints to murder of the
      surgeon. After an evaluation of the special problems related to change, I chose
      to reduce the amount of hump resected and to restrict the elevation of the nasal
      tip-nasolabial angle to a minimum compatible with normal appearance. The purpose
      is to avoid the tag of "operated nose." Some illustrative cases are shown. The
      goal is presented as precision, discretion, and satisfaction. Sometimes, doing
      less is more.

PMID- 8746467
TI  - Mucous cyst: postrhinoplasty complication.
AB  - Inclusion cysts are one of the few complications found after a rhinoplasty. We
      report on a patient that developed a postrhinoplasty mucous cyst.

PMID- 8746468
TI  - Subperiosteal facelifting: complications and the dissatisfied patient.
AB  - As endoscopic subperiosteal lifting of the upper face is explored, it may
      significantly limit the indications for the open approach. However, this report
      is based on our combined large experience and long follow-up in open bicoronal
      subperiosteal lifting. The combined experience of four surgeons in four countries
      with an open subperiosteal approach to lifting of the upper face in 545 patients
      is described. The complications of the procedure, both common and rare, and
      techniques to avoid untoward effects are discussed. Reasons for patient
      dissatisfaction are addressed. Based on their evaluation of results and
      complications of the surgery over a 6-year period (1986-1992), we conclude that
      subperiosteal lifting is an effective, reliable, reproducible, and safe
      operation.

PMID- 8746469
TI  - Complex SMAS-platysma and senility.
AB  - Following an anatomic study of 18 hemifaces, the authors show the modifications
      to and the behavior of the complex SMAS-platysma in the process of senility.
      Through this investigation, they succeeded in better understanding the anatomic
      modifications to the face's deep structures caused by the loss of tonicity and
      consequent flaccidity of the integument upon them. The investigation also showed
      the ligamentary fixations existing among the SMAS, the parotid-masseteric fascia,
      the major and minor zygomatic muscles, and the adherences of the platysma to the
      mandible periosteum.

PMID- 8746470
TI  - The tumescent technique facilitates hair micrografting.
AB  - Micrografting for hair restoration has become increasingly popular because of the
      natural results it can achieve. The procedure is often performed under local
      anesthesia or local anesthesia with sedation. To achieve adequate anesthesia,
      supraorbital and supratrochlear nerve blocks are often performed as well as
      infiltration of the donor and recipient areas via multiple needle injections.
      These nerve blocks and multiple injections are associated with significant
      discomfort and may need to be repeated if anesthesia is inadequate. In addition,
      because of the rich vascularity of the scalp, donor site and recipient bed
      bleeding are often encountered, making the procedure more difficult and
      increasing postoperative bruising and morbidity. In an attempt to alleviate these
      difficulties and increase patient comfort, the tumescent technique was employed
      in 50 consecutive micrografting procedures. The ability to achieve anesthesia in
      the donor and recipient beds without the need for additional nerve blocks was
      evaluated. The ability of the tumescent technique to minimize bleeding and
      subsequent postoperative ecchymosis and morbidity was analyzed. The findings of
      this study suggest the tumescent technique is useful in facilitating hair
      micrografting. It consistently achieves excellent anesthesia in both donor and
      recipient sites without the need for multiple needle injections or nerve blocks.
      The duration of anesthesia is significant, allowing completion of the procedure
      and offering prolonged postoperative anesthesia as well. Bleeding can be
      minimized using the tumescent technique for both donor site harvesting and the
      micrografting procedure itself.

PMID- 8746471
TI  - Comprehensive liposuction of lower limbs: basic concepts.
AB  - The basic concepts of the aesthetics of proportioning the lower limb region by
      liposuction are discussed. The operative technique and some clinical cases are
      also discussed.

PMID- 8746473
TI  - Full facelift through an endoscopic approach.
AB  - Full facelift through an endoscopic approach has been indicated for young
      individuals without significant skin excess but with mild laxity of the midface.
      It also has been indicated in secondary rhytidoplasty. Wide undermining of the
      face and neck is performed. Liposuction at submental and submandibular areas
      provides noticeable improvement for the neck and mandibular contour. Plication of
      the SMAS and platysma muscle is used to replace tissues and to regain a youthful
      appearance. Improved results become evident when plication is performed over the
      deformity. The unlikely course for the SMAS and platysma plication is to provide
      an aesthetic balance for the face and neck. Extracorporeal knotting is used to
      hold the folded muscle in position. In addition, scars are minimal and occur in
      areas where they cannot be seen. However, selection criteria must be followed to
      achieve excellent results with this procedure.

PMID- 8746472
TI  - Evaluation of the KTP 532 laser in aesthetic facial surgery.
AB  - This study investigated the ability of the KTP 532 laser to reduce postoperative
      swelling and bruising in aesthetic facial surgery. Thirty consecutive patients
      receiving a laser-assist procedure (following skin incision with a scalpel,
      dissection and hemostasis were accomplished primarily with the laser) were
      compared to 16 patients who had similar technical operations but relied on
      scissor/scalpel dissection and electrocautery for hemostasis. Evaluations were
      performed by comparison of serial photographs after surgery and by patient self
      assessment. The clinical observations demonstrated a noticeable reduction in
      postoperative swelling, bruising, and discomfort in the patients whose procedure
      was performed with the aid of the laser.

PMID- 8746474
TI  - The 16th Annual Maliniac Lecture. Plastic surgery in Taiwan: building a
      cathedral.

PMID- 8746475
TI  - Reduction mammaplasty by central pedicle flap with short submammary scar.
AB  - Reduction mammaplasty was performed in 30 patients by combining the central
      pedicle flap method with the short submammary scar (3-S) technique to avoid the
      common drawbacks of currently popular dermoglandular procedures. Reduction was
      accomplished by using perforating vascular branches from the pectoralis major
      muscle and its fascia supplying the nipple and breast parenchyme instead of the
      subdermal plexus. The central vascular pedicle supplying the nipple-areola
      complex was preserved. Only the periphery of the breast parenchyme was resected
      circumferentially, with the exception of the inferolateral portion, so as not to
      injure the sensory nerve. The remaining breast parenchyme was preserved in an
      inverted cone shape. The nipple-areola complex was safely transposed with great
      freedom, and the amount of resection was accurately adjusted for symmetry. No
      cases of nipple-areola complex sensory change occurred postoperatively, and
      lactation is possible because of preservation of the lactiferous ducts. The
      length of postoperative scars was reduced by using the short submammary scar
      technique. We believe this combined method is ideal in patients requiring
      resections ranging from 200 to 600 g per breast with good skin elasticity and
      moderate degree of ptosis.

PMID- 8746476
TI  - Reduction mammaplasty: a comparison of outpatient and inpatient procedures.
AB  - A review of the procedure, postoperative outcome, and expense of outpatient
      inferior pedicle reduction mammaplasty was compared with inpatient hospital
      treatment. Twenty outpatient procedures were compared with an equal number of
      inpatient procedures. Medical and social backgrounds of the two patient
      populations were similar. The findings indicate that bilateral breast reduction
      can be performed safely and cost-effectively as an outpatient procedure.

PMID- 8746477
TI  - Phenol peeling: new standards of excellence.
AB  - Phenol peeling remains the gold standard of chemical peeling because no other
      agent can compare in the treatment of patients with moderate and deep rhytids.
      However, phenol peeling can be very painful and is associated with many
      tradeoffs. Plastic surgeons have boldly modified their approach to TCA peeling to
      improve their results and we would like to see the same applied to phenol
      peeling. The purpose of this article is to initiate new thinking about phenol
      peeling and to correct misconceptions that commonly appear in the literature. By
      modifying our technique we have been able to perform virtually painless phenol
      peels and to reduce the tradeoffs commonly seen. Our modifications are discussed
      in detail along with a discussion of the new concepts we feel are supported by
      our experience.

PMID- 8746478
TI  - Aesthetic considerations in facial reconstructive surgery: the V-Y flap
      revisited.
AB  - The subcutaneous pedicled V-Y advancement flap (also known as the "kite flap" of
      Dufourmentel) has been described by many authors. Its versatility in
      reconstructive surgery is well known, both in facial reconstructive surgery as
      well as surgery of the trunk and extremities. Its advantages in achieving
      aesthetic reconstruction in specific facial regions have been less well
      emphasized in the literature. The flap can be designed within natural facial
      creases and heals inconspicuously because of its widely based subcutaneous or
      muscle pedicle which incorporates venous and lymphatic drainage over most of its
      length. The undesirable "biscuiting" or flap edema frequently observed with other
      conventional transposition flaps is avoided. We have found the V-Y flap
      particularly useful in reconstructing the lower eyelid/medial canthus, supra
      alar, and nasolabial regions. Our experience with over 40 such flaps is
      described, and technical considerations in designing and elevating the flap are
      discussed.

PMID- 8746479
TI  - Inhibition of alpha1-adrenoceptor-mediated contractions in isolated tail arteries
      and aorta of the rat by alpha2-adrenoceptor agonists.
AB  - The effects of alpha2-adrenoceptor agonists, clonidine, tizanidine and UK-14304
      on alpha1-adrenoceptor-mediated contractile responses were studied in isolated
      tail arteries and thoracic aorta of the rat. When applied during sustained
      contractile responses to almost maximum concentration (10 microM) of
      phenylephrine, clonidine (0.3 microM to 100 microM) produced concentration
      dependent relaxations in both tissues. The maximum relaxation was smaller in tail
      arteries than in thoracic aorta. Clonidine up to 100 microM failed to relax both
      tissues precontracted with KCl (60 microM) or U-46619 (1 microM), a thromboxane
      mimetic. The clonidine-induced relaxation in tail arteries, was reversed by
      alpha2-adrenoceptor antagonists, yohimbine and idazoxane. Effects of the alpha2
      adrenoceptor antagonists were concentration-dependent (0.1 microM to 1 microM),
      but not in a competitive manner. On the other hand, the relaxation in thoracic
      aorta was not significantly antagonized by these alpha2-adrenoceptor antagonists.
      Tizanidine and UK-14304 also relaxed both tail arteries and thoracic aorta
      precontracted with phenylephrine. The characteristics of the relaxation and their
      antagonism by yohimbine in both arteries were similar to those induce by
      clonidine. In tail arteries, NG-nitro-L-arginine, a nitric oxide synthase
      inhibitor, at a concentration that completely inhibited acetylcholine-induced
      relaxations did not significantly affect the relaxation induced by clonidine. In
      contrast, the relaxation of thoracic aorta in response to clonidine was partly
      reduced in the presence of NG-nitro-L-arginine. These results indicate that the
      alpha2-adrenoceptor agonists selectively inhibit the contractions induced by
      phenylephrine in both tissues. Regional differences in the modes of the
      inhibition by the alpha2-adrenoceptor agonists exist.

PMID- 8746480
TI  - Effects of RO 5-4864 and PK 11195 on guinea pig trachea.
AB  - Previous reports have suggested a role played by peripheral benzodiazepine
      receptors (PBZ) in the regulation of calcium. The aid of this investigation was
      to evaluate the effects of Ro 5-4864 (PBZ agonist) and PK11195 (PBZ antagonist)
      in guinea pig trachea and their possible role in the regulation of calcium. Ro 5
      4864 and PK 11195 showed spasmolytic effects on the contraction curve induced by
      acetylcholine. Moreover, Ro 5-4864, PK 11195 and diltiazem (a Ca2+ -antagonistic
      drug) shifted to the right the contraction curves induced by acetylcholine,
      potassium chloride (KCl), calcium chloride (CaCl2), or by Bay K 8644. These
      results demonstrate that the benzodiazepines and their antagonists may exhibit
      Ca2+ -antagonistic activity. Ro 5-4864 and PK 11195 may exert this effect at a
      site that is a component of, or is associated with, voltage operated calcium
      channels (VOC).

PMID- 8746481
TI  - Relaxant effects of berberine on the rat fundus.
AB  - The present study examines the relaxant effect of berberine on the longitudinal
      muscle of the isolated rat gastric fundus. Our experiments show that berberine
      reduces the tonic contraction more than the phasic contraction induced by
      carbachol. In addition, the carbachol induced phasic contraction in Ca+2 -free
      solution was only inhibited at the highest concentration of berberine. Berberine
      inhibited the slow phase more than the fast phase in KCl-induced contractions.
      These results suggest that the major mechanism of berberine consists of an
      inhibition of calcium entry from extracellular in the second phase induced by
      both carbachol and KCl. Conversely, prevention of the mobilization of store Ca+2
      in the phasic contraction phase induced by carbachol and prevention of the
      calcium entry from extracellular in first phase elicited by high levels of
      potassium play only a minor role in the dilatory effect of berberine.

PMID- 8746482
TI  - Stability, tissue metabolism, tissue distribution, and blood partition of DA
      1131, a new carbapenem.
AB  - The stability of DA-1131 after incubation in various pH solutions, human plasma,
      human urine, human gastric juice, rat liver homogenates and rat whole blood, the
      disappearance of DA-1131 after incubation in the 9000g supernatant fraction of
      various rat tissue homogenates in the presence of NADPH, the tissue distribution
      of DA-1131 after intravenous (i.v.) administration of DA-1131, 50 mg/kg, to rats,
      and the blood partition of DA-1131 between plasma and blood cells from rabbit
      blood were studied. DA-1131 was unstable when incubated in various pH solutions,
      especially at low and high pHs at the DA-1131 concentration of 10 micro g/ml; the
      degradation half-lives of DA-1131 were 0.260, 1.23, 2.20, 7.16, 14.2, 10.5, 31.3,
      21.3, 0.262, 0.241, and 1.45 hr for pH solutions of 1-11, respectively. DA-1131
      was also unstable after incubation in human plasma, rat liver homogenates, and
      human gastric juice. However, DA-1131 seemed to be sable in human plasma for up
      to 12 hr storage at -20 degrees C. The spleen, kidney, liver, lung, mesentery,
      and stomach homogenates from rats showed metabolic activity to DA-1131. The
      tissue-to-plasma ratios of DA-1131 were lower than unity in all tissues studied
      except kidney when each tissue was collected at 30 min after i.v. administration
      of DA-1131 to rats. The tissue-to-plasma ratios of DA-1131 were lower than unity
      in all tissues studied except kidney when each tissue was collected at 30 min
      after i.v. administration of DA-1131 to rats. The plasma-to-blood cell
      concentration ratios of DA-1131 were independent of DA-1131 blood concentrations
      when the whole blood was incubated up to 120 min; the mean values were 5.56 +/-
      1.47, 5.80 +/- 2.19, and 4.61 +/- 1.82 at DA-1131 blood concentrations of 2, 10,
      and 20 microgram/ml, respectively, rabbits A-C. There was also considerable in
      vivo and in vitro blood storage effect in the plasma concentration of DA-1131 in
      rabbits.

PMID- 8746483
TI  - Relative zinc-binding capacity of metallothionein: studies in renal cytosols from
      zinc-injected rats.
AB  - Each rat was injected intraperitoneally once with 0.9% NaCl or zinc (10, 20, 40,
      or 60 mg zinc/kg b.w.). The zinc content in kidney reached a maximum level of
      approx. 50 microgram/g kidney, corresponding to a dose (40 mg zinc/kg b.w.). The
      distribution profiles of the renal cytosols of zinc-injected rats on a Sephadex G
      75 column showed that most of the increased zinc was attributable to
      metallothionein. There was a linear relationship between the zinc contents in
      cytosol and metallothionein. Our results demonstrated that there was a limit of
      zinc accumulation in kidneys of zinc-injected rats and that 57% of the increased
      zinc in renal cytosols was bound to metallothionein. Our results suggest that the
      role of metallothionein in zinc accumulation in the kidney is similar to that of
      zinc accumulation in liver.

PMID- 8746484
TI  - Rapid formation of multicellular spheroids composed of Propionibacterium acnes
      pretreated adult rat liver cells by rotary culture and their immunological
      properties.
AB  - An experimental acute liver injury model can be produced by the injection of
      bacterial lipopolysaccharide (LPS) into Propionibacterium acnes (P. acnes)
      pretreated rats. The massive liver cell necrosis is estimated by elevation of
      serum transaminase activities. In this study, we produced this necrosis in an in
      vitro model by using primary co-cultured rat liver cells. A novel method for the
      preparation of spheroids consisting of P. acnes pretreated parenchymal and
      nonparenchymal liver cells has been successfully developed quickly by the rotary
      culture system within 24 hr although it takes 7 days to form the spheroid using a
      collagen-conjugated thermo-responsive polymer such as a cell substratum. Clear
      elevations of transaminase activities, TNF-alpha and CINC-1/gro/KC leaked from
      these spheroids into the medium caused by the exposure of 10 microgram/ml LPS for
      48 hr were observed. These results suggest that this rotary co-culture system of
      rat liver cells is a useful model as an alternative to animal tests for fulminant
      hepatitis.

PMID- 8746485
TI  - Reduction of dietary phosphorus absorption by oral phoshorus binders.
AB  - The aim of this study was to study a possible new non-aluminum phosphate-binder
      to limit hyperphosphatemia in patients with renal failure. Zirconyl chloride
      octahydrate was evaluated as a dietary phosphate binder in rats. Aluminum
      chloride hexahydrate was used as a reference. Animals were divided into six
      groups (6 animals per group): One - control group (C), two - aluminum groups (Al1
      and Al2) and three - zirconium groups (Zr1, Zr2 and Zr3) receiving different
      doses of zirconyl chloride octahydrate. Urines were collected during the
      experimental period. At the end of the treatment, the animals were sacrified and
      plasma and different organs were collected (liver, spleen, kidneys, brain and
      femur). Determination of phosphorus and calcium levels in plasma indicated that
      zirconyl chloride octahydrate yielded as good results as aluminum chloride
      hexahydrate did. Zirconyl chloride octahydrate significantly (p<0.01) reduced
      bone phosphorus burden. Urinary excretion of phosphorus indicated a severe
      phosphorus depletion in all treatments. Not even traces of zirconium could be
      determined in the different tissues, in urines or in plasma. Consequently, it is
      important to carry out experiments with zirconium compounds in order to develop
      non-aluminum-containing phosphate binders.

PMID- 8746486
TI  - AZT modulation of trimetrexate myelotoxicity: evidence from an HL60 model.
AB  - AZT is widely used in combination with other potentially myelotoxic drugs. Bone
      marrow suppression may limit the vigor of therapy directed at HIV itself,
      opportunistic infections, and/or AIDS-associated malignancies. Evidence from an
      HL60 model suggests that toxicity is of most concern with simultaneous use of
      multiple agents, and that staggered use of different agents may in some cases be
      a more effective strategy.

PMID- 8746487
TI  - Plasma levels of type II phospholipase A2 and cytokines in patients with sepsis.
AB  - Plasma levels of type II phospholipase A2 (type II PLA2), cytokines and endotoxin
      were determined in patients with sepsis to investigate their interrelations and
      their role in the patient's prognosis. Type II PLA2 was measured by
      radioimmunoassay, tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6),
      and IL-8 were each measured by enzyme-linked immunosorbent assay (ELISA).
      Endotoxin was determined by a method based on an endotoxin-specific synthetic
      substrate. Plasma levels of type II PLA2 were significantly higher in the
      patients who died of sepsis than in those who survived the illness. There was a
      significant correlation between type II PLA2 and TNF-alpha and IL-6. Type II
      PLA2, TNF-alpha, IL-6, and IL-8 may be useful as indices of disease severity. The
      results suggest that TNF-alpha and IL-6 stimulate the production of type II PLA2
      in the plasma of patients with sepsis.

PMID- 8746488
TI  - Relationship between contractile responses and cytosolic free calcium levels in
      response to phorbol ester (PMA) in isolated rat aorta.
AB  - We examined the relationship between phorbol ester (PMA)-induced contractile
      response and cytosolic free calcium level in the rat aorta. PMA (10(-6)M)
      produced biphasic contraction, i.e., sustained contraction followed by a phasic
      response superimposed on the sustained contraction. Increase in [Ca2+]i was
      accompanied by a phasic but not sustained contraction. These results suggest that
      PMA-induced phasic contraction is dependent on Ca2+ influx but sustained
      contraction may be due to an increase in Ca2+ sensitivity of contractile protein.

PMID- 8746489
TI  - Stress and depressive symptoms prospectively predict immune change among HIV
      seropositive men. HIV Neurobehavioral Research Center Group.
AB  - LIFE stress, mood, and other psychosocial factors may help to explain variability
      in HIV (human immunodeficiency virus) disease progression. Attempts to support
      this notion empirically have produced mixed findings; several studies report a
      positive relationship between psychosocial factors and various indicators of
      disease progression or immune function (e.g., Evans et al. 1992; Goodkin et. al.
      1992), whereas others have failed to detect any association (e.g., Perry et. al.
      1992).

PMID- 8746490
TI  - Psychoeducation in first-episode psychosis: a therapeutic process.
AB  - THE importance of psychoeducational work with the relatives of patients with
      psychotic illness has been increasingly emphasized in recent years (Anderson et
      al. 1986). This has resulted partly from research showing that providing support
      and information for families is of value in reducing relapse rates as well as
      assisting relatives directly, and partly from the emergence of highly effective
      organizations of relatives advocating on behalf of the families of the severely
      mentally ill (Sokas 1986). A puzzling aspect of this development is the relative
      lack of interest in the psychoeducational needs of the patients themselves. As
      Smith et al. (1992) point out, few researches or clinicians have focused on this
      issue and only one controlled study has been carried out (Goldman and Quinn
      1988). Eckman et al. (1992) reported the results of a controlled trial of
      modularized illness self-management skills training versus supportive group
      psychotherapy and found some advantage for the former intervention, which
      involved some elements of psychoeducation. However, the patients were suffering
      from well-established schizophrenia and had been ill for many years, so the
      timing of the interventions was less than optimal.

PMID- 8746491
TI  - Narrative and psychological understanding.
AB  - NARRATIVE understanding is based in philosophical hermeneutics, a tradition
      regnant in Europe but only recently penetrating the American intellectual
      consciousness. Within this epistemology, there is only the text (communicated in
      language), which is itself about a text, and dialogue within and among these
      texts. There is no priori place to stand to make truth claims: there are only
      interpretations made from a particular historical and value-implicated stance.
      The "hermeneutic circle" describes a process in which understanding requires
      reference to a priori understandings such that knowledge accrues in a circular,
      dialectic fashion. No knowledge can be independent of context or interpreter. The
      enterprise of science then becomes conversation from which emerge consensual
      ideas that constitute ways of perceiving and interpreting future texts.

PMID- 8746492
TI  - Boundaries in psychotherapy: model guidelines.
AB  - THE maintenance of boundaries in psychotherapy is now one of the most critical
      areas of ethical inquiry for psychiatrists and other mental health professionals.
      Sexual contact between therapists and patients-the most egregious example of
      boundary violation-has received a good deal of attention (Gabbard 1994), and a
      firm consensus regarding its inappropriateness has developed (American
      Psychiatric Association 1992b; American Psychological Association 1992). But
      public concern over nonsexual boundary violations is growing, as witnessed by
      highly publicized cases in the media (Kagan 1988; Karel 1993), rulings by
      licensure bodies (In the Matter of Aronoff 1992), and lawsuits (Jorgenson and
      Sutherland 1993). Evidence from all of these sources suggests that the task of
      defining appropriate boundaries in psychotherapy is complex and confusing for
      therapists, regulators, and the public alike.

PMID- 8746493
TI  - The case for not interpreting unconscious mental life in consulting to
      organizations.
AB  - DESPITE differing theoretical orientations in psychoanalysis, there is general
      agreement that its distinctive feature among all therapies is its attempt to
      bring to consciousness mental conflict that is unconscious. Does this distinctive
      feature of psychoanalysis apply in organizational consultation? I argue that
      unlike clinical psychoanalysis, more harm than good occurs when consultants
      attempt to interpret unconscious material to clients in organizations. The main
      use of psychoanalytic psychology in consulting work is for observation and
      understanding on the part of the consultant, who as an advisor presents
      recommendations aimed at enhancing rationality.

PMID- 8746494
TI  - Nonlinear dynamical patterns as personality theory for neurobiology and
      psychiatry.
AB  - ADVANCES in the theory of nonlinear differential equations and their statistical
      representations have yielded a powerful, qualitatively descriptive yet
      quantitative language that captures characteristic patterns of behavior (what the
      psychoanalyst Roy Schafer calls "continuity, coherence, and consistency of
      action") that has begun to influence studies of complex systems in motion as
      diverse in specifics as signatory patterns of discharge of neurochemically
      defined single neurons and the dynamical structures characteristic of a
      particular composer's music. What might be called personality theories of
      neurobiological dynamics have arisen to replace neurobiological theories of
      personality. It is in this way that rigorously proven and powerful general
      mathematical insights have changed the face of determinism in research in brain
      and behavior. Two examples: (1) Very complicated looking behavior of
      neurobiological forced-dissipative (expanding and contracting) systems over time
      take place on low dimensional abstract surfaces on which only a few underlying
      abstract parameters control the action. (2) Independent of specific details
      (chemical, electrical, and/or behavioral), there exist a relatively few
      fundamental categories of behavior in time and transitions, among them a property
      called universality. Results from this new theoretical, in contrast with
      experimental, reductionism yield analogies with and new approaches to
      historically important dynamic ideas about personality and character patterns
      that are equally relevant to micro and macrocomplex systems such as neural
      membrane receptor proteins and individual personality styles. Research findings
      achieved over the past decade and a half in our laboratory and others in
      neurochemistry, neurophysiology, and animal and human behavior, as well as the
      results of a new demonstration experiment involving the prediction of dynamical
      category membership from abstract expressive motion in humans, are used to
      exemplify this use of a quantitative dynamic category theory across disciplinary
      levels in brain and behavior. Multiple measures of complexity adapted from
      current research in the statistical properties of chaos on unobtrusively observed
      and reconstructed orbits on the computer screen made by non-premorbid subjects
      executing content-free, computer-game-like tasks with a mouse, were used to
      reliably differentiate the "signatures" of two Axis II diagnoses as established
      using SCID-II criteria. Whereas the techniques of nonlinear systems have achieved
      some success in quantifying and stimulating the dynamical styles of relatively
      local phenomena such as the spontaneous behavior of neuronal membrane
      conductances, single neurons, neural networks, and field electrical events, we
      think that the real power of these techniques lies in their quantitative
      description and statistical prediction of global patterns of behavior of entire
      systems. For example, since the late 1970s our work has shown that these measures
      could be used to discriminate categories of drug action and dose when applied to
      patterns of rat exploratory behavior in space and time. The combination of
      abstract generality and quantitative precision of these methods suggests their
      usefulness as a cross-disciplinary language for fields like psychiatry that deal
      with complicated behavior of both neurobiological elements and "the whole
      person."

PMID- 8746495
TI  - Work and meaning: disturbance of volition and vocational dysfunction in
      schizophrenia.
AB  - R. is a 40-year-old, divorced, White male with a diagnosis of schizophrenia,
      paranoid type, chronic. Shortly after his entrance into our work rehabilitation
      program, R. engaged one of the authors (P.L.) in a conversation about the nature
      of his illness. He reported that his most disabling and pervasive symptom was a
      persistent inability to pursue any goal in his life. R. recognized that he had
      other symptoms of psychiatric illness but stated that these did not account for
      his disability. He explained that the voice of God that counseled him when he
      felt overwhelmed and his fear that God was about to kill him as punishment for
      his sins put life in perspective and, consequently, were sometimes as comforting
      as they were distressing. R. explained that what had altered his life was a
      process, invisible to others, that left him unable to plan out and pursue a life
      course. He did not know whether it was a lack of knowledge or lack of motivation
      and energy that left him without the inner direction he needed. All he knew was
      that it was "schizophrenia," and it left him unable to work or to function like
      other people. What R. was describing as the foundation of his illness and his
      disability appears to be a disturbance of volition. Interestingly, self
      understanding is more consistent with several of the early formulations of
      schizophrenia than it is with current formulations. To explore the merits of R.'s
      belief about his illness we offer a review of the role that disturbance of
      volition has played in historical conceptualizations of schizophrenia, the
      current nosology, and in theories of the negative or deficit syndrome. The
      history of R.'s illness is then presented. Lastly, we discuss what we learned
      from R.'s participation in a paid work program.

PMID- 8746496
TI  - Personal myths about work and mental illness: response to Lysaker and Bell.

PMID- 8746497
TI  - A commentary on Donald B. Lindsley's "Life and reflections of a psychologist
      psychophysiologist from a personal and historical perspective".

PMID- 8746498
TI  - Life and reflections of a psychologist-psychophysiologist from a personal and
      historical perspective.

PMID- 8746499
TI  - Tracing the planned probe trajectory on axial computed tomography slices: a
      computation-based support for stereotactic procedures. A computational tool for
      tracing of probe trajectories on CT slices.
AB  - Stereotactic frames are designed to hit point-like intracranial targets. Their
      routine performance does not include a display of the intended transcerebral
      probe path. Since the latter can render stereotactic procedures safer, more
      accurate and versatile, it has increasingly been implemented by potent computer
      systems. A low-cost alternative is presented in the form of a small extension of
      the computation program which is usually employed for the conversion of imaging
      coordinates to frame adjustments. It allows any desired point on the planned
      probe trajectory, in terms of its distance to the target, to be defined in
      Cartesian coordinates and thus to be traced on computed tomography. Thus, in
      biopsy procedures, for instance, instead of sampling tissue at the target only or
      in a 'blind' serial way, samples can be collected in a previewed and therefore
      safer and more purposeful way, thereby improving the yield of pathological
      tissue. The method seems particularly interesting for institutions that have a
      low to moderate number of stereotactic procedures and for which the investment of
      sophisticated computer systems for this purpose alone would not be economically
      feasible.

PMID- 8746500
TI  - CT analysis of postoperative changes after thalamotomy for Parkinson's disease.
AB  - Stereotactic operations have long been used to relieve agitation and muscle
      rigidity in Parkinson disease. Because of its high-density resolution, CT is
      quite effective to portray the location, size, shape and density of the
      thermocoagulative focus. The foci were classified into different types according
      to their changes in different time periods. Correlation with pathological changes
      was discussed.

PMID- 8746501
TI  - Stereotactic volumetric radiofrequency lesioning of intracranial structures for
      control of intractable seizures.
AB  - Computed tomography (CT) scans provide three-dimensional information about
      intracranial structures, which can be used to place stereotactically guided
      radiofrequency (RF) lesions and destroy a targeted volume of tissue. This
      technique was used for lesioning of the corpus callosum (CC) or the amygdala
      hippocampus complex (AHC) in 9 patients with intractable seizures. The procedures
      were monitored by intraoperative CT scans. Lesions were made in the AHC in 7
      patients and the CC in 2 patients. In addition, multiple subpial transection
      (MST) was performed in 6 patients. The longest follow-up is 29 months with a
      median of 19 months. Five patients (56%) are free of seizures, 3 patients (33%)
      have greater than 90% reduction in seizure activity and 1 patient (11%) has
      greater than 50% but at most 90% reduction in seizure activity. There were no
      complications except for temporary hemiparesis following MST in 1 patient. The
      results suggest that stereotactic volumetric RF lesioning of the AHC and the CC
      may be safe and effective in controlling intractable seizures.

PMID- 8746502
TI  - Symptomatic cyst of the septum pellucidum treated by stereotactic
      intraventricular drainage.
AB  - Symptomatic cavum septi pellucidi is a rare occurrence. Clinically, it can
      manifest with persistent or intermittent symptoms of internal hydrocephalus and
      consciousness disorders, simulating a colloid cyst of the third ventricle,
      possibly with mental symptoms, focal deficits, epilepsy, ataxia and pyramidal
      signs. This is a case of a 24-year-old woman with persistent symptoms of
      hydrocephalus due to obstruction of the foramina of Monro produced by a cyst of
      the septum pellucidum. The condition was successfully treated by stereotactic
      ventriculocystotomy.

PMID- 8746503
TI  - Response of extra-axial tumors to stereotactically implanted high-activity 125I
      seeds.
AB  - 125I seeds can deliver a very high dose of radiation (100-500 Gy) to a well
      circumscribed area over their average life of 87 days, which enable them to
      destroy slow-growing extra-axial tumors after permanent implantation.
      Stereotactic implantation of 125I seeds was performed in 26 patients with extra
      axial tumors, with a median follow-up of 32 months. No acute morbidity or
      mortality resulted from the procedure. Cranial nerve involvement in 5 patients
      was the only delayed complication. One patient developed radionecrosis outside
      the range of 125I dose distribution, which was felt to be due to the
      hyperfractionated external radiation the patient had received prior to 125I seed
      placement. All 26 patients showed tumor regression. The results indicate that
      this form of treatment is relatively safe and effective in the management of
      extra-axial tumors.

PMID- 8746504
TI  - Epidural spinal cord stimulation in the management of spasms in spinal cord
      injury: a prospective study.
AB  - Forty-eight spinal cord injury victims were implanted with an epidural spinal
      cord stimulation system to treat spasms that had not satisfactorily responded to
      medical therapy. All the patients were at least 6 months after the injury. The
      protocol included assessment by independent examiners preoperatively and at 3, 6,
      12 and 24 months after the implant. Pre- and postoperative data collection
      included the frequency and severity of the spasms. Combining the frequency and
      intensity scores into a 'severity' score provided a more accurate clinical
      picture. No patient observed neurological deterioration following the surgical
      procedure or the neurostimulation treatment. A statistically significant
      reduction in the severity of the spasms was observed in the follow-up
      evaluations, with results that progressively increased in time. It is appears
      that spinal cord stimulation is an effective and safe alternative in the
      management of spasms in spinal cord injury victims. Its exact role in relation to
      intrathecal baclofen infusion and ablative procedures remains to be defined.

PMID- 8746505
TI  - Effect of middle ear on otoacoustic emissions.
AB  - Otoacoustic emissions (OAEs) are believed to originate from outer hair cell
      movement and are considered to be transmitted to the external auditory meatus
      through the middle ear in a retrograde fashion. Therefore, the effect of the
      middle-ear on OAEs seems to be large. However, few investigations of middle-ear
      effects on OAEs have been published because no apparatus that can measure the
      middle-ear dynamic characteristics is easily available except a conventional
      impedance meter. We developed a sweep frequency impedance meter (SFI) which gives
      us much more information on middle-ear dynamic characteristics than a
      conventional impedance meter. In this paper, applying SFI and 3 OAE measuring
      apparatuses, middle-ear dynamic characteristics and different sorts of OAEs of
      human subjects and guinea pigs were measured, and an attempt was made to examine
      the relationship between OAEs and middle-ear dynamic characteristics from various
      aspects. It is concluded that frequency characteristics of OAEs correlate well
      with middle-ear frequency characteristics; and middle-ear effect on OAEs must be
      taken into account when OAE data are analyzed.

PMID- 8746506
TI  - Reliability of auditory brainstem responses from sequenced high-frequency (> or =
      8 kHz) tonebursts.
AB  - An auditory brainstem response method is described for evoking responses to 4
      high-frequency (8, 10, 12 and 14 kHz) tonebursts in the same amount of time
      normally required to obtain responses to single tonebursts. Reliability of
      responses to high-frequency toneburst stimuli presented in the conventional
      manner (one at a time) has been previously documented. In the present study, high
      frequency tonebursts were presented to 20 normal-hearing subjects singly and in a
      4-stimulus sequence. The reliability of resulting responses did not differ
      significantly between single- and multiple-stimulus test conditions. It is
      concluded that this sequenced-stimulus concept could be developed for use in
      serial monitoring of individuals receiving ototoxic agents as well as being
      broadly applicable to clinical situations in which patients cannot or will not
      respond voluntarily.

PMID- 8746507
TI  - Auditory-evoked response morphology in profoundly-involved multi-handicapped
      children: comparisons with normal infants and children.
AB  - The developmental and difference/defect theories have been used to explain
      auditory development in some multi-handicapped children. If developmental factors
      influence auditory response behaviors, it might be predicted that evoked
      potentials measured from the central auditory nervous system would reflect
      similar developmental influences in multi-handicapped children. The purpose of
      this study was to compare auditory-evoked-potential waveform morphology between
      profoundly-involved multi-handicapped children and normal infants and children.
      Auditory brainstem response (ABR) and middle-latency response (MLR) morphology
      were examined from waveform descriptions, wave detection, latency, amplitude, and
      spectral energy measures. The majority of handicapped subjects exhibited response
      morphology unlike that of normal children or infants. ABR/MLR morphology for
      handicapped children was characterized by depressed responses and substantial
      waveform variability. The results of this study tended to support the
      difference/defect theory.

PMID- 8746508
TI  - Rehabilitation of hearing-impaired children: intervention and outcome.
AB  - A cohort of 72 hearing-impaired children of a median age of 9.7 years, range 4.3
      13.9, born during 1980-1990 and living in the health district of Copenhagen City
      was examined cross-sectionally in order to evaluate the interval from
      identification to the initial fitting of hearing aids (HAs) and children's use of
      HAs. As measures of outcome, the use of HAs at 1, 6, 12 months after fitting, and
      at the time of data collection was assessed along with the primary language of
      each child. One month after the fitting, 53% of the total sample used the HAs > 8
      h/day, and no significant longitudinal changes in the proportion of time-related
      use were found. 56% of the children stayed in the same user category during the
      years, while the rest either increased (25%) or decreased (19%) the use of
      amplification from 1 month after fitting to the time of data collection. Children
      with better ear hearing level (BEHL) 0.5-4 kHz between 60 and 89 dB used the HAs
      significantly more than those with mild or profound hearing impairments, whereas
      age at onset (congenital, acquired, age at onset unknown) and age at intervention
      were unrelated to use of amplification. 72% of the children were oral, while 25%
      were manual (unknown 3%), and no differences in the use of HAs were found between
      these two groups. A subdivision of congenitally hearing-impaired children
      according to BEHL 0.5-4 kHz below/above 75 dB demonstrated a significantly larger
      proportion of manual children in the poorer hearing group despite a significantly
      younger amplification age. It is concluded that age at intervention is unrelated
      to primary language, although the number of children precludes dependable
      conclusions.

PMID- 8746509
TI  - Endoplasmic reticulum Ca(2+)-ATPase in microsomal vesicles isolated from bovine
      retinae.
AB  - Active Ca2+ transport was measured in microsomal vesicles prepared from bovine
      retinae and was compared with that in disk membranes of the photoreceptor cells
      of the same retina. The 45Ca uptake was dependent on the presence of Mg(2+)-ATP
      and was inhibited by vanadate or when GTP substituted for ATP. The dependence of
      calcium uptake on the external free Ca2+ concentration gave a KM = 13 microM or a
      KM = 0.1 microM for disks and microsomal vesicles, respectively. A phosphorylated
      intermediate (E-P) of Ca(2+)-ATPase of about 100 kDa was isolated in microsomal
      vesicles. The E-P formation was strongly inhibited by thapsigargin and partially
      by 2,5-di-(-butyl)benzohydroquinone. Digestion of disks or microsomes with
      calpain had no effect on the phosphorylated intermediate, while digestion with
      trypsin produced two fragments of approximately 55 kDa and 35 kDa. These results
      suggest that bovine retinal microsomes contain a calcium pump belonging to the
      SERCA family.

PMID- 8746510
TI  - HPLC analysis of cyclic adenosine diphosphate ribose and adenosine diphosphate
      ribose: determination of NAD+ metabolites in hippocampal membranes.
AB  - Cyclic adenosine diphosphate-ribose (cADPR) and ADPR were separated by high
      performance liquid chromatography (HPLC) on a CarboPac PA-1 column at strong
      basic pH and quantitated by a pulsed amperometric detector. Although this HPLC
      method was quite sensitive and highly reproducible, it did not allow the
      separation of cADPR from guanosine monophosphate (GMP) which, when present, could
      be removed by ion-affinity chromatography, using gel-immobilized Fe3+ columns.
      Crude synaptic membranes from rat hippocampi were incubated with nicotinamide
      adenine dinucleotide (NAD) and acidic extracts were subject to HPLC analysis
      after neutralization. Incubation led to a time-dependent formation of ADPR, which
      was amplified when membranes were incubated in the presence of guanosine
      trisphosphate (GTP), guanosine-5'-0-(3-thiotrisphosphate) (GTP-gamma-S) or AlF3.
      cADPR did not accumulate in detectable amounts and only a minimal proportion (<
      5%) of radioactivity originating from [3H]NAD co-eluted with authentic cADPR in
      extracts from hippocampal membranes. The simultaneous detection of cADPR and ADPR
      we have described may help the search for inhibitors of cADPR metabolism, which
      will allow to measure the cADPR that accumulates under basal conditions or in
      response to extracellular signals.

PMID- 8746511
TI  - Neuroprotective and deleterious effects of nitric oxide on focal cerebral
      ischemia-induced neurone death.

PMID- 8746512
TI  - Nitric oxide in the liver: physiopathological roles.
AB  - Many of the known roles of arginine (e.g. in immune function, wound healing, and
      protection against ammonia intoxication) are mediated by a metabolic pathway
      synthesising nitric oxide (NO) in the liver. Contrary to some of the current
      views, liver-produced NO may be basically beneficial, as it exerts both
      protective actions against tissue injury and cytotoxic effects on invading
      microorganisms, parasites, or tumor cells. An ongoing equilibrium between NO and
      other NO-reactive compounds (e.g. O2 and non-heme iron-sulphur-containing
      moieties) appears to be important in this respect, even under critical
      conditions. Thus, NO may prevent liver tissue harm from oxidant stress. Only when
      this putative counterbalance is upset by an uncontrolled, prolonged and/or
      massive production of NO, liver tissue damage may occur leading to hepatic
      inflammation or even tumor development. Moreover, the currently available data
      support the working hypothesis that hepatocytes partake not only to
      immunoregulatory processes, but even to immune defence mechanisms. Thus, the
      liver constitutes an excellent model for investigations into the crosstalks
      regulating the production of NO which take place among not only the various
      networks operating inside a single hepatic cell, but even the individual types of
      liver cells.

PMID- 8746513
TI  - Mechanisms for nitric oxide-induced cell death: involvement of apoptosis.
AB  - Recent observations suggest that apoptosis, the natural, active cell death
      process is also triggered in several pathological conditions including ischemic
      brain insult, and neuro-degenerative and autoimmune diseases. We have
      investigated the mechanisms involved in the development of apoptosis in neuronal
      and pancreatic cells and in macrophages, which were exposed to either chemical
      donors of nitric oxide or to inducers of the nitric oxide synthase. In this
      overview, we summarize current evidence for the involvement of apoptosis in the
      cytotoxicity of nitric oxide and discuss possible mechanisms that may lead to
      cell death.

PMID- 8746514
TI  - Release of nitric oxide from astroglial cells: a key mechanism in neuroimmune
      disorders.
AB  - Astrocytes are glial cells able to release nitric oxide (NO) under basal
      conditions as well as following different neurochemical stimuli including
      cytokines, endotoxins and soluble antigens, thereby participating in neuroimmune
      responses. In particular, the inducible isoform of NO synthase seems to be
      activated during co-incubation of this cell type with cytokines as well as in the
      presence of the HIV coating gp120 glycoprotein, an effect which is associated
      with an enhancement of prostanoid release. This seems also to occur via
      activation of cyclooxygenase by NO. Thus, the L-arginine-NO pathway found in
      astrocytes may represent a novel approach in the treatment of neuroimmune
      disorders such as multiple sclerosis, Alzheimer's disease and AIDS.

PMID- 8746515
TI  - NO-synthase: what can research on invertebrates add to what is already known?
AB  - The present study attempts to review presently known data regarding the
      distribution of nitric oxide (NO) synthase and the function of NO in invertebrate
      species. NO is synthesized from L-arginine by the enzyme NO-synthase, and
      activates guanylate cyclase which in turn leads to an increase in levels of cGMP
      in target cells. Major contributions to the knowledge of NO as a messenger
      molecule in invertebrates have been made by NADPH-diaphorase histochemistry and
      biochemical assays. These techniques suggest the presence of a L-arginine/NO
      pathway in a variety of tissues, thus implicating multiple roles for NO in
      invertebrates.

PMID- 8746516
TI  - Role of nitric oxide in cell-mediated tumor cytotoxicity.
AB  - Strong and increasing evidence shows that nitric oxide (NO) contributes to immune
      function, and in particular to 'non-specific host defense'. The aim of the
      present review was to focus the current understanding of the role of NO as a
      biochemical effector of L-arginine-dependent cell-mediated immune responses to
      neoplastic cells in vitro and in vivo. The cytokine-inducible nitric oxide
      synthase (NOS) seems to mainly be implicated in the cytotoxic activity of almost
      all the effector cells involved in tumor cell killing. The cytotoxic actions of
      NO against tumor cells appear to be related mainly to inhibition of several heme
      containing enzymes of the mitochondrial electron transport complex and the citric
      acid cycle.

PMID- 8746517
TI  - Nitric oxide: an ancestral immunocyte effector molecule.
AB  - The presence and the role of nitric oxide synthase (NOS) were investigated in the
      molluscan hemocytes by immunocytochemical, biochemical and functional approaches.
      Using an anti-NOS polyclonal antibody, immunoreactivity was observed in the
      hemocytes, and this reactivity increased after stimulation of the animals with
      Escherichia coli, indicating that this enzyme is inducible. The NOS inducibility
      was also histochemically demonstrated by detection of NADPH-diaphorase activity.
      Biochemical studies show that the enzyme is 70% cytoplasmatic and 30% membrane
      bound and that the inducible form is mainly cytoplasmatic. The nitrite + nitrate
      and citrulline formation, the inhibition by N omega-nitro-L-arginine, the Km
      value for arginine, the calcium and co-enzyme dependence show that the molluscan
      NOS shares the same properties as the NOS isoenzymes so far studied. However, it
      cannot be identified with any of these enzymes. It appears to be in some way
      similar to an inducible form of human hepatocyte NOS. Also cytokines are able to
      induce NOS. In vitro studies have shown that hemocytes produce nitric oxide (NO),
      a bactericide substance, and that there is a relationship between the NO system
      and phagocytosis. The presence of NO in the invertebrate hemocyte demonstrates
      that critical molecules have been conserved over the course of evolution.

PMID- 8746518
TI  - Detection of endothelial cell-derived nitric oxide: current trends and future
      directions.
AB  - The vascular endothelium is a significant site of NO release that inhibits
      cellular adhesion and maintains a non-thrombogenic surface. Use of newly
      described technology suggests for the first time that the maximal release of NO
      induced by cNOS and iNOS activation may be quite similar, implying that it is the
      duration of NO release and not the concentration of NO produced from stimulated
      endothelial cells that accounts for the different biological activities of the
      enzymes. The respective roles of cNOS and iNOS must be carefully evaluated since
      both enzymes may have potent biological effects at local sites of production.

PMID- 8746519
TI  - Induction of nitric oxide in cultured microglia: evidence for a cytoprotective
      role.

PMID- 8746520
TI  - Surgical correction of severe vaginal introital stenosis in female baboons (Papio
      sp.) infected with simian agent 8.
AB  - Simian agent 8 (SA8) is a neurotropic, endemic alphaherpesvirus in Papio sp.
      Lesions associated with simian agent 8 infections usually involve the genitalia
      of sexually mature baboons. In females, secondary bacterial infections may lead
      to scarring of the vulva and perineum, with resulting vaginal obstruction.
      Affected baboons are poor breeders and often develop urinary tract infections due
      to retention of urine in the vagina. Reconstructive vaginal surgery was performed
      on seven baboons with vaginal obstruction. Four weeks before surgery, 50 mg of
      Depo-Provera was administered intramuscularly to each animal to arrest the
      estrous cycle, reduce swelling, and allow adequate surgical exposure of the
      vagina. Ventral and circular incisions were made around the constricted vagina.
      The peripheral skin was excised to break down the underlying connective tissue,
      allowing access to the vaginal mucosa. Healthy vaginal tissue was then opposed to
      the incised skin edges with 3-0 Vicryl in an interrupted pattern. Once healed,
      the vaginas remained patent, allowing normal mating and urination. Nine months
      after surgery, five baboons had healthy infants, and pregnancy was confirmed in
      the other two animals. The described procedure may allow female baboons
      previously infertile and at risk of urinary tract infections to be returned to a
      healthy reproductive state.

PMID- 8746521
TI  - Isolation of mycoplasmas from prairie voles (Microtus ochrogaster).
AB  - A new species of mycoplasmas was isolated from the lungs and nasopharyngeal
      washings of prairie voles (Microtus ochrogaster). Clinical signs of disease and
      microscopic lesions were not observed at the time of this isolation. The organism
      was cultured in SP4 medium; it grew aerobically, anaerobically, and in 5% CO2 in
      5 to 7 days, and fermented glucose. Transmission electron microscopy revealed the
      organism to lack a cell wall and to have typical mycoplasmal ultrastructural
      morphology. The complete nucleotide sequence of the 16S rRNA gene from an isolate
      was determined by amplification with polymerase chain reaction and by sequencing
      with the dideoxynucleotide chain termination method. The sequence did not match
      any known sequences in the GenBank of the National Institutes of Health. The 16S
      rRNA sequence of the organism, Mycoplasma volis (proposed species novum), is
      unique and most closely resembles that of M. muris and M. iowae. Because this
      vole colony will be housed in rooms with other rodents, pathogenicity studies of
      this new species of mycoplasmas in mice and rats are underway.

PMID- 8746522
TI  - Proliferative lesions of the testis in ad libitum-fed and food-restricted Fischer
      344 and FBNF1 rats.
AB  - The effect of 40% food restriction on spontaneous proliferative lesions of the
      testis was evaluated in lifetime and cross-sectional (serial sacrifice) studies
      of 419 Fischer (F-344) and 304 Fischer x Brown Norway (FBNF1) male rats.
      Interstitial cell hyperplasia and interstitial cell adenoma (ICA) were the most
      common proliferative lesions in each genotype; incidence of each was less in the
      FBNF1. In each genotype, food restriction delayed the onset of both lesions and
      reduced the incidence of ICA. At 12 months interstitial cell hyperplasia was
      present in 11 of 12 ad libitum (AL)-fed and 0 of 12 food-restricted (FR) F-344
      rats. In FBNF1 rats interstitial cell hyperplasia was observed first at 18 months
      in AL-fed and at 36 months in FR groups. Interstitial cell adenoma developed in 5
      of 12 AL-fed F-344 rats by 18 months and in 2 of 12 FR rats by 24 months; 2 of 12
      AL-fed FBNF1 rats had ICA at 30 months, and 1 of 12 FR rats had ICA at 42 months.
      In these cross-sectional studies approximately half the ICA cases in F-344 rats
      were bilateral; no FBNF1 rats had bilateral ICA. In lifetime studies the
      incidence of ICA was reduced from 49% in AL-fed rats to 19% in FR F-344 rats and
      from 9% in AL to 4% in FR FBNF1 rats. The incidence of mesothelioma was low in
      both genotypes and was not obviously altered by food restriction. A malignant
      embryonal neoplasm, an unclassified benign neoplasm, and three seminomas were
      present in the testes of FBNF1 rats.

PMID- 8746523
TI  - Production of recombinant hantavirus nucleocapsid protein expressed in silkworm
      larvae and its use as a diagnostic antigen in detecting antibodies in serum from
      infected rats.
AB  - The recombinant nucleocapsid protein (rNP) of Hantaan virus was expressed by a
      baculovirus vector in silkworm hemolymph and was used as an antigen in western
      blotting (WB). The rNP is expressed in insoluble form in hemolymph; therefore
      simple washing of the insoluble fraction with phosphate-buffered saline by low
      speed centrifugation allowed preparation of purified antigen for WB. The rNP had
      strain-specific and hantavirus-common epitopes similar to the authentic NP
      antigen of hantavirus and was stable after transfer to membrane. For detection of
      antibody in serially obtained sera from experimentally infected rats, WB enabled
      detection of IgM antibodies 3 days after infection, which was at least 2 days
      earlier than detection by the indirect immunofluorescent antibody test (IFA).
      Thus WB had a higher sensitivity than the IFA for detection of hantavirus
      antibody in the serum of experimentally infected rats. The WB-determined IgG
      antibody titer was about 10 times higher than that determined by the IFA. No
      background staining was observed by WB even at a 1:10 dilution of serum. The
      selected rat sera with strong background staining or confusing staining patterns
      by IFA, but not focus reduction neutralization test titers, could be interpreted
      as test-negative because they did not have a specific reaction to virus antigen
      by WB. Thus the specificity of WB was higher than that of the IFA. Moreover, WB
      can distinguish specific from nonspecific reactions by the detection of the
      specific antigen on the WB membrane. Therefore the IFA or enzyme-linked
      immunosorbent assay followed by WB is recommended for serologic confirmation of
      hantavirus infection.

PMID- 8746524
TI  - A canine model for determination of the therapeutic index of cytokine inhibitors.
AB  - Using tumor necrosis factor (TNF) inhibition in dog blood as a measure of
      efficacy, and canine emesis as a measure of toxicity, we were able to assign a
      therapeutic index to rolipram, a prototypic anti-inflammatory compound. Because
      both assays were performed in the same species, the ambiguities associated with
      comparing the physiologic effects of drugs on various species was avoided.
      Rolipram, a standard phosphodiesterase type IV inhibitor, was a prototypic test
      compound characterized by a number of cardiovascular and central nervous system
      side effects, as well as its in vitro and in vivo inhibition of TNF. Initial
      experiments with canine whole blood incubated with lipopolysaccharide resulted in
      nanogram-per-milliliter concentrations of TNF that could be significantly reduced
      by in vitro addition of a 0.03 microM concentration of rolipram. Because rolipram
      inhibited canine TNF production in vitro, a protocol was devised in which TNF
      inhibitory activity was measured in a series of blood samples from dogs infused
      with increasingly high doses of rolipram. This yielded the efficacy half of the
      therapeutic index, whereas the emetogenic dose represented the side effect
      portion of the index. Rolipram was infused stepwise into conscious dogs at
      gradually increasing doses. The infusion was stopped when vomiting occurred, and
      the cumulative dose was reported as the emetic dose. Rolipram caused emesis in
      dogs at a cumulative dose of 0.1 mg/kg. At each dose of rolipram, blood was
      collected. The whole blood was incubated in vitro with lipopolysaccharide to
      induce TNF production, which in turn was quantified by the L929 bio-assay.
      Theoretically, if the rolipram infusion raised blood values high enough, the
      rolipram in whole blood would inhibit TNF production and be reflected by a lack
      of TNF activity in the L929 assay. In this assay system, rolipram's 50% effective
      dose in the TNF assay was always at least 33-fold lower than its emetic dose of
      0.1 mg/kg. This gave rolipram a therapeutic index of at least 33:1 (0.003 versus
      0.1 mg/kg) on the basis of its activity in a canine efficacy model (TNF
      inhibition) and a toxicity model (emesis induction). Experimental compounds were
      tested for their emetic dose as well as TNF 50% effective dose, with the goal of
      obtaining a therapeutic index better than that of rolipram. Thus the coupling of
      cytokine activity with overt toxicity was used to arrive at the therapeutic index
      of a compound. The therapeutic index was used to rank compounds as to their
      efficacy/toxicity profile. This ranking was used to eliminate several anti
      inflammatory compounds that had a therapeutic index less than that of rolipram.

PMID- 8746525
TI  - Protective effects of macrophage-derived interferon against encephalomyocarditis
      virus-induced diabetes mellitus in mice.
AB  - The involvement of macrophages in protection against diabetes mellitus in mice of
      BALB/c (susceptible) and C57BL (resistant) strains infected with the B (non
      diabetogenic) or D (highly diabetogenic) variant of encephalomyocarditis (EMC)
      virus was examined. Pretreatment with the B variant of EMC virus (EMC-B),
      avirulent interferon (IFN) inducer, or Corynebacterium parvum inhibited diabetes
      in BALB/c mice infected with the D variant of EMC virus (EMC-D). Treatment of
      C57BL mice with carrageenan to compromise macrophage function rendered C57BL mice
      susceptible to EMC-D-induced diabetes. In macrophage culture for BALB/c mice, EMC
      B induced IFN at an earlier stage than did EMC-D. The C57BL mouse-derived
      macrophages produced more IFN than did BALB/c mouse-derived macrophages after
      stimulation with EMC-D. Moreover, C. parvum increased IFN production in
      macrophage cultures from BALB/c mice, whereas carrageenan inhibited that in
      macrophage cultures from C57BL mice. These results suggest that IFN derived from
      macrophages may have an important role in protecting mice against EMC virus
      infection.

PMID- 8746526
TI  - Dietary induction of cholesterol gallstones in the owl monkey: preliminary
      findings in a new animal model.
AB  - The owl monkey (Aotus nancymae) is a primate with a bile acid and biliary lipid
      profile resembling that of humans. Aotus spp. are among the rare species,
      including humans, that spontaneously develop cholesterol gallstones. With dietary
      induction the owl monkey proved a rapid, reliable model of cholesterol
      cholelithiasis. Six owl monkeys, three of each sex, were fed a diet supplemented
      with 1.5% cholesterol for 5 weeks. Each week blood samples were drawn for
      cholesterol determination, and bile samples were obtained by ultrasound-guided
      percutaneous aspiration of the gallbladder. Weekly ultrasound imaging documented
      development of gallbladder sludge in all animals, with eventual stone formation
      in five of six. At necropsy after 5 weeks consuming the diet, all animals had
      distinct sludging and/or small stones in the gallbladder, correlating with the
      ultrasound findings. Plasma cholesterol values remained lower in females but
      increased markedly in some males to > 1,400 mg/dl. Histologic examination
      revealed mild, diffuse hepatocellular lipidosis and degeneration in four of six
      animals. Detailed examination of the gallbladder indicated that transhepatic
      needle punctures induced minimal focal abnormalities, judged inconsequential. In
      contrast to rodent models commonly in use, owl monkeys have liver and digestive
      tract anatomy and bile physiology that is similar to that in humans. These
      similarities give this model the potential to substantively improve understanding
      of the pathogenesis, treatment, and prevention of human cholesterol gallstones.
      This model can provide sequential, simultaneous correlation of plasma and biliary
      lipids, imaging of gallbladder contents, and physiologic processes.

PMID- 8746527
TI  - Hepatic and adrenal changes in rabbits associated with hyperlipidemia caused by a
      semi-synthetic diet.
AB  - Several investigators have reported that feeding a semi-synthetic diet of casein
      and dextrose to New Zealand White (NZW) rabbits will increase total serum
      cholesterol concentration, principally through an increase in the beta
      lipoprotein fractions, thereby creating a useful model for atherosclerosis
      research. Although there is evidence to suggest that the dextrose/casein diet
      alters low-density lipoprotein receptor and bile acid clearance of cholesterol,
      the underlying mechanism is not completely understood. The effects of the diet on
      the overall physiology of the rabbit have received little attention. In this
      study feeding a diet of casein and dextrose of male NZW rabbits for 4 weeks
      resulted in changes in the serum lipid concentrations. During that time the
      rabbits fed the dextrose/casein diet gained less weight than did control rabbits.
      In the test diet rabbits, liver aspartate and alanine transaminase activities
      were increased from baseline values of 27 +/- 2 U/L and 89 +/- 9 U/L respectively
      to 112 +/- 21 U/L and 281 +/- 34 U/L respectively, then returned to the high end
      of the reference range. Necropsy findings included hepatomegaly caused by
      vacuolar hepatopathy in 19 or 20 experimental rabbits; rabbits fed the control
      diet had no hepatic lesions. Ultrastructural analysis revealed that enlargement
      of the liver cells was due to glycogen deposition. Adrenal glands from animals
      fed the experimental diet had a minimal change in the size of the adrenocortical
      cells consisting of slight ballooning and rarefaction of the cytoplasm. In a
      second study the level of dietary fiber was doubled. This resulted in a three
      fold increase in lipid concentrations, compared with the fivefold increase in the
      first study. The liver enzyme activities were increased to the same extent as in
      the first study. Histologic changes were comparable to those in the first study.
      The activity of hepatic cholesterol 7alpha-hydroxylase was 3.7 +/- 0.4
      pmol/min/mg of protein, compared with the control value of 7.7 +/- 1.1
      pmol/min/mg of protein (P < 0.05) in the second study. The improved rate of
      weight gain and the lesser increase in total serum cholesterol concentration in
      the second study with increased dietary fiber suggest that two separate
      activities may be involved. Although the level of dietary fiber may be related to
      weight gain and total serum cholesterol values, the relation to the decrease in
      liver transaminase activities in study 1 was probably coincidental. It appears
      that the dextrose/casein diet causes decreased activity of hepatic cholesterol
      7alpha-hydroxylase, which could cause a decrease in the biliary excretion of
      cholesterol.

PMID- 8746528
TI  - Establishment of the hereditary cataract rat strain (SCR) and genetic analysis.
AB  - The Shumiya cataract rat (SCR) and normal control rat strains of NC1 and NC2 were
      established. Mean cataract appearance in adult SCR rats was 66.7%, and embryo
      death rate was 25%. Genetic analysis of cataract formation in the SCR was studied
      by breeding experiments with strains such as NC1, BUF, ACI, AD3, and normal SCR
      rats. No sex-based differences in cataract appearance were observed in any of the
      progeny. These results confirmed our hypotheses that two autosomal genes, a
      recessive cataract gene (ctr1), and a normal allele of a dominant cataract gene
      with a recessive lethal trait (Ctr2(1)) for provisional designations participated
      in cataract genesis in SCR (ctr1/ctr1, Ctr2(1)/Ctr2) rats. One recessive cataract
      gene was maintained in normal SCR, NC1 and NC2 (ctr1/ctr1, Ctr2/Ctr2) rats. The
      same recessive cataract gene was retained in the albumin-deficient brown hooded
      rat strain AD3 (ctr1/ctr1, Ctr2/Ctr2).

PMID- 8746529
TI  - Magnetic resonance imaging of the normal mouse brain: comparison with histologic
      sections.
AB  - Details in the living animal can be compared with respective histologic section
      taken after death. In less than 35 min, 12 to 16 coronal and transverse images
      through the brain can be obtained, each with an in-plane resolution of 100 x 200
      microns and a slice thickness of 900 microns. The experimental parameters can be
      manipulated not only to achieve different tissue contrast but also to access any
      desired plane.

PMID- 8746530
TI  - Diagnostic exercise: hepatomegaly in an aged cynomolgus (Macaca fascicularis)
      monkey.

PMID- 8746531
TI  - Chronic catheterization of the intestines and portal vein for absorption
      experimentation in beagle dogs.

PMID- 8746532
TI  - Left ventricular function in a dog with left anterior fascicular block.

PMID- 8746533
TI  - Transvenous phrenic nerve stimulation during prolonged mechanical ventilation in
      awake, nonparalyzed ewes.

PMID- 8746534
TI  - Transplantation of the diaphragm in rats.

PMID- 8746535
TI  - Use of butorphanol as an anesthetic adjunct in turkeys.

PMID- 8746536
TI  - Effects of neuropeptides on growth of cultivated rat molar pulp fibroblasts.
AB  - The effect of the neuropeptides substance P (SP), neurokinin A (NKA), calcitonin
      gene-related peptide (CGRP), neuropeptide Y (NPY) and vasoactive intestinal
      polypeptide (VIP) on DNA synthesis of dental pulp cells was investigated in cells
      grown from molar tooth bud explants from 4-6 days old rat pups. A concentration
      response-assay of the proliferative response of pulpal cells was performed with
      SP, NPY, NKA, CGRP and VIP (0.01 to 1 nM) in the presence of EGF (10 ng/ml),
      hydrocortisone (0.4 microgram/ml) and 3% FCS, using [3H]thymidine incorporation.
      The results showed that SP, NKA and CGRP, but not NPY and VIP, increased the cell
      number in a concentration-dependent manner, with maxima at 10(-10)-10(-9) M (SP,
      NKA) and 10(-7) M (CGRP). No potentiating effect was noted when cells were
      simultaneously stimulated with SP and CGRP. The finding that SP, NKA and CGRP
      have growth regulatory properties on pulpal cells in vitro suggests that sensory
      neuropeptides may be involved during pulpal development or in wound healing after
      pulpal injury.

PMID- 8746537
TI  - Structural modifications of non-mammalian gonadotropin-releasing hormone (GnRH)
      isoforms: design of novel GnRH analogues.
AB  - Three natural forms of vertebrate gonadotropin-releasing hormone (GnRH) provided
      the structural basis upon which to design new GnRH agonists: [His5,Trp7,Leu8]
      GnRH, dogfish (df) GnRH; [His5,Asn8]-GnRH, catfish (cf) GnRH; and
      [His5,Trp7,Tyr8]-GnRH, chicken (c) GnRH-II. The synthetic peptides incorporated
      the position 6 dextro (D)-isomers D-arginine (D-Arg) or D-naphthylalanine (D-Nal)
      in combination with an ethylamide substitution of position 10. The in vitro
      potencies for LH and FSH release of these analogues were assessed using static
      cultures of rat anterior pituitary cells. Efficacious peptides were examined for
      their gonadotropin-II and growth hormone releasing abilities from perifused
      goldfish pituitary fragments. Rat LH and FSH release was measured using
      homologous radioimmunoassays, whereas goldfish growth hormone and gonadotropin-II
      release were determined using heterologous carp hormone radioimmunoassays. The
      receptor binding of the most potent analogues was determined in bovine pituitary
      membrane preparations. Substitution of D-Nal6 into [His5,Asn8]-GnRH increased the
      potency over 2200-fold compared with the native ligand (cfGnRH) in cultured rat
      pituitary cells. This was equivalent to a 55-fold greater potency than that of
      the native mammal (m) GnRH peptide. Substitution of D-Nal6 or D-Arg6 into dfGnRH
      or cGnRH-II resulted in potencies that were related to the overall hydrophobicity
      of the analogues. The [D-Nal6,Pro9NEt]-cfGnRH bound to the bovine membrane
      preparation with an affinity statistically similar to that of [D-Nal6,Pro9NEt]
      mGnRH (kd = 0.40 +/- 0.04 and 0.55 +/- 0.10 nM, respectively) in cultured rat
      pituitary cells. All analogues tested released the same ratio of FSH to LH. In
      goldfish, the analogues did not possess superagonistic activity but instead
      desensitized the pituitary fragments at lower analogue doses than that of the
      sGnRH standard suggesting differences in receptor affinity or signal
      transduction.

PMID- 8746538
TI  - Chronic systemic treatment with epidermal growth factor in the rat increases the
      mucosal surface of the small intestine.
AB  - We examined the effects of treatment with human recombinant epidermal growth
      factor (EGF) on the functioning small intestine in the rat. Male Wistar rats, 7-8
      weeks old, were treated with EGF administered subcutaneously in doses of 0 (n =
      7) or 150 micrograms/kg/day (n = 8) for 4 weeks. The histological composition and
      mucosal surface area of the perfusion-fixed small intestine was quantified with
      stereological principles. The length of the gut remained unchanged. The amount of
      tissue and surface area per length of gut (median (ranges)) were increased from
      117 (101-131) mg/cm and 2.6 (2.1-3.5) cm2/cm in the controls to 146 (138-152)
      mg/cm and 3.5 (2.5-3.8) cm2/cm for the complete small intestine (both comparisons
      P < 0.02). The weight increase was due to mucosal growth in all parts of the
      intestine, whereas the surface area was only increased in proximal and middle
      parts. It is concluded that EGF treatment in rats increases the mucosal weight
      and surface area of the functioning small intestine.

PMID- 8746539
TI  - Activity of amylin at CGRP1-preferring receptors coupled to positive contractile
      response in rat ventricular cardiomyocytes.
AB  - Calcitonin gene-related peptide (CGRP) exerts a positive contractile response
      directly in rat ventricular cardiomyocytes. This response is mediated by
      receptors of the CGRP1-subtype. Amylin is 46% homologous with CGRP and binds to
      receptors selective for CGRP in a range of tissues. The ability of amylin to
      influence ventricular contractility has been assessed using cardiomyocytes
      isolated from the ventricles of adult rats. Cardiomyocytes were subjected to
      biphasic electrical stimulation at 0.5 Hz. CGRP produced a concentration
      dependent positive contractile response which became maximal 4 min after initial
      stimulation. CGRP increased the contractile amplitude maximally at 1 nM and to a
      value which was 23.3% greater than in the absence of peptide (EC50 value = 21
      pM). Amylin increased the contractile amplitude maximally at 20 nM and to a value
      which was 17.3% greater than in the absence of peptide (EC50 value = 216 pM). In
      the presence of amylin (20 nM), the concentration-dependence of the contractile
      response to CGRP was shifted to the left, so that the response became maximal
      when CGRP was present at 50 pM. In the presence of CGRP8-37 (100 nM), a selective
      antagonist at CGRP1-preferring receptors, the concentration-dependence of the
      contractile response to CGRP was shifted to the right (dose ratio = 54).
      Similarly, in the presence of CGRP8-37 (100 nM), the contractile response to
      amylin was inhibited significantly (P < or = 0.01). Amylin8-37 (100 nM) did not
      inhibit the concentration-dependence of the contractile responses to CGRP and
      amylin significantly (dose ratios = 4.2 and 2.4, respectively). In conclusion,
      these data indicate that amylin exerts a contractile response directly in rat
      ventricular cardiomyocytes via CGRP1-preferring receptors. This effect could
      assume greater significance in non-insulin-dependent diabetes mellitus and in
      hypertensive states, in which the concentration of amylin is elevated in plasma.

PMID- 8746541
TI  - High levels of vasoactive intestinal peptide/pituitary adenylate cyclase
      activating peptide receptor mRNA expression in primary and tumor lymphoid cells.
AB  - Neuropeptides exert a variety of putative immunomodulatory actions. Despite the
      molecular cloning of multiple forms of receptors for several neuropeptides with
      putative immunomodulatory effects, including vasoactive intestinal peptide (VIP),
      the related peptide pituitary adenylate cyclase-activating peptide (PACAP), the
      opiate peptides, tachykinins, somatostatin and corticotropin-releasing factor, it
      has not been reported that any of the receptor genes are expressed at significant
      levels in cells of the immune system. The low level of expression of these
      receptors and lack of knowledge concerning receptor subtype has impeded progress
      in understanding how neuropeptides regulate immune function. For example, it is
      not understood why VIP produces immunomodulatory effects at concentrations far
      below its receptor-binding affinity. Receptors for VIP and PACAP have recently
      been cloned. We show here by Northern blot analysis that the VIP/PACAP1 receptor
      mRNA is present in total RNA prepared from mouse spleen B- and T-lymphocytes. The
      VIP/PACAP1 receptor mRNA was also present in human peripheral blood lymphocytes,
      and in a B-lymphocyte and a myelocytic cell line. The mRNA for a second form of
      the receptor, the VIP/PACAP2 receptor, was not expressed at detectable levels in
      normal cells, but was detected in several human T-cell lines and a murine mast
      cell line. The results indicate that VIP/PACAP1 and perhaps VIP/PACAP2 receptors
      mediate the diverse effects of VIP and PACAP on immune cells.

PMID- 8746540
TI  - A functional comparison of the rat type-1 angiotensin II receptors (AT1AR and
      AT1BR).
AB  - To evaluate and functionally compare the rat AT1A and AT1B receptor subtypes,
      stable Chinese hamster ovary (CHO) cell lines expressing either recombinant
      receptor in approximately equal numbers were generated. Radioligand binding data
      suggests that the recombinant AT1A receptor is pharmacologically similar to the
      recombinant AT1B receptor. Functional studies indicate that both receptor
      subtypes can independently activate the phospholipase C/IP3 and the
      dihydropyridine-sensitive voltage-dependent Ca2+ channel signal transduction
      pathways with equal efficiency, but are unable to modulate cAMP accumulation
      under our experimental conditions. Furthermore, both receptors can be directly
      involved in the cellular growth properties of AII. Slot-blot experiments clearly
      demonstrate that these receptors are expressed in a tissue-specific manner. A
      sequence comparison of the 5' flanking regions of these two genes shows that they
      have very little sequence homology (approximately 36%), suggesting that although
      the AT1A and AT1B receptors appear to be pharmacologically and functionally
      similar, the control of their expression seems to be governed by distinct
      transcription factors.

PMID- 8746542
TI  - Stimulation of natural killer (NK) and antibody-dependent cellular cytotoxicity
      (ADCC) activities in murine leukocytes by bombesin-related peptides requires the
      presence of adherent cells.
AB  - Bombesin and the two mammalian bombesin-related peptides, gastrin-releasing
      peptide (GRP) and neuromedin C, at physiological concentrations have been
      previously shown to stimulate significantly in vitro the antibody-dependent
      cellular cytotoxicity (ADCC) and natural killer (NK) activities in BALB/c mouse
      leukocytes from axillary nodes, spleen and thymus. In the present work we have
      shown that adherent cells are required in leukocyte samples for stimulation of
      cytotoxicity by the neuropeptides, which suggests that this effect may be
      mediated by those cells. Here we demonstrate the specificity of the effects by
      reversing them in the presence of the bombesin-antagonist (Leu13-psi CH2NH-Leu14)
      BN, and by detecting specific receptors for GRP on macrophages of high and low
      affinity. Using the same binding technics, no receptors for this neuropeptide
      were found in non-adherent leukocytes.

PMID- 8746543
TI  - Characterization and distribution of bombesin binding sites in the goldfish
      hypothalamic feeding center and pituitary.
AB  - Bombesin (BBS)/gastrin-releasing peptide (GRP) binding sites were characterized
      and their distribution examined in the goldfish brain and pituitary by
      radioligand binding and autoradiography. Binding of 125I-[Tyr4]-BBS-14 to tissue
      sections was found to be saturable, reversible, time-dependent and displaceable
      by BBS/GRP-like peptides. Analysis of saturable equilibrium binding revealed a
      one-site model fit with a Kd of 0.665 +/- 0.267 nM. This binding site displayed
      high affinity for members of the BBS subfamily of peptides, including GRP10 (Ki;
      0.292 +/- 0.038 nM) and GRP27 (Ki; 2.034 +/- 1.597 nM), but showed no affinity
      for the BBS8-14 fragment. While an approximate 100-fold lower binding affinity
      was displayed by the binding site for neuromedin B (Ki; 6.15 +/- 28.2 nM),
      litorin was highly effective in displacing radiolabeled BBS binding (Ki; 1.469 +/
      0.427 nM). The localization of saturable and high affinity BBS/GRP binding sites
      in specific areas of the goldfish brain and pituitary generally revealed a
      similar anatomical distribution to BBS/GRP-like immunoreactive material reported
      previously by our laboratory. Quantitative densitometric analysis of radiolabeled
      BBS binding to brain nuclei and the pituitary revealed a moderate concentration
      of BBS/GRP binding sites in the hypothalamic feeding area, including the nucleus
      diffusus libi inferioris, nucleus recessus lateralis, nucleus lateral tuberis,
      and nucleus anterior tuberis. Other brain nuclei known to influence the brain
      feeding center which contained a high density of BBS/GRP binding sites included
      nuclei of the dorsal and ventro-medial telencephalon, the preoptic hypothalamus,
      and the optic tectum. High densities of BBS/GRP binding sites were also localized
      in the dorsal cerebellum, and nucleus habenularis. In the pituitary, BBS/GRP
      binding sites were present in high concentration in the neurointermediate lobe,
      with a relatively lower density localized in the pars distalis. The present study
      further supports a role for BBS/GRP-like peptides in the regulation of feeding
      behavior and anterior pituitary hormone secretion in teleosts.

PMID- 8746544
TI  - Synthetic peptides corresponding to residues 551 to 555 and 650 to 653 of the rat
      testicular follicle-stimulating hormone (FSH) receptor are sufficient for post
      receptor modulation of Sertoli cell responsiveness to FSH stimulation.
AB  - We have recently demonstrated that synthetic peptides corresponding to the third
      cytoplasmic (3i) loop (residues 533 to 555) and a region in the carboxy-terminal
      cytoplasmic tail (residues 645 to 653) of the rat testicular follicle-stimulating
      hormone receptor (FSHR) affected signal transduction in rat testis membranes and
      cultured rat Sertoli cells. In order to define more precisely the peptide domains
      involved, we synthesized truncated peptide amides corresponding to FSHR residues
      551-555 (KIAKR) and 650-653 (RKSH), respectively. These two regions were chosen
      since they contained a minimal structural motif present in G protein activator
      regions of several other G protein-coupled receptors (i.e., B-X-X-B-B or B-B-X-B,
      B representing a basic amino acid). Neither peptide inhibited binding of FSH to
      testis membrane receptors. Each peptide significantly reduced FSH-stimulated
      estradiol biosynthesis by intact cultured rat Sertoli cells. The same results
      were obtained with streptolysin O-permeabilized Sertoli cells. No effect was
      noted on forskolin-induced steroidogenesis, indicating that the peptide effects
      were not due to interaction with adenylyl cyclase. Each peptide amide, however,
      induced concentration-dependent increases in guanine nucleotide exchange in rat
      testis membranes. Our results indicate that interaction of FSH receptor with its
      associated G protein may involve relatively restricted peptide sequences, and
      include residues 551-555 (KIAKR) in the third cytoplasmic loop, and residues 650
      653 (RKSH) in the carboxy-terminal cytoplasmic tail of the FSH receptor.

PMID- 8746545
TI  - Pancreatic polypeptide, microinjected into the dorsal vagal complex, potentiates
      glucose-stimulated insulin secretion in the rat.
AB  - Specific binding sites for circulating pancreatic polypeptide (PP) have been
      found within the dorsal vagal complex (DVC) in the caudal medulla oblongata.
      Therefore, the effects of rat PP on pancreatic hormone secretion upon its
      microinjection into the DVC in halothane-anesthetized rats at doses of 0.4-40
      pmol were investigated. At this range of doses, the changes in plasma
      concentrations of insulin, glucagon and glucose over basal levels did not differ
      from those after vehicle microinjection. In a separate series of experiments,
      vehicle and PP at doses of 0.4 and 4 pmol were microinjected into the right DVC
      40 min after the continuous infusion of D-glucose had been started. In animals
      receiving continuous infusion of D-glucose, PP microinjected into the DVC (4
      pmol), resulted in markedly higher insulin levels at corresponding time points
      compared to those with vehicle microinjected into the DVC. These data indicate,
      for the first time, that microinjection of PP into the DVC may potentiate glucose
      stimulated insulin secretion in halothane-anesthetized rats.

PMID- 8746546
TI  - Effects of pituitary adenylate cyclase-activating polypeptide on cardiovascular
      and respiratory responses in anaesthetised dogs.
AB  - This study examines some of the cardiovascular and respiratory effects of
      pituitary adenylate cyclase-activating polypeptide (PACAP) in anaesthetised dogs.
      Intravenous injection of PACAP 27 caused an increase in arterial blood pressure
      and an increase in heart rate. The blood pressure response was significantly
      reduced by adrenoceptor blockade suggesting a mechanism of action mediated in
      part via catecholamines. The heart rate increase was unaltered by adrenoceptor
      blockade suggesting a direct effect of PACAP 27. PACAP 27 also caused
      potentiation of cardiac slowing caused by stimulation of the vagus nerve. In
      addition, PACAP 27 powerfully stimulated breathing. This was probably evoked by
      stimulation of arterial chemoreceptors, because bilateral section of the carotid
      sinus nerves abolished this effect. PACAP 27 had no effect on the ability of the
      cardiac sympathetic nerve to increase heart rate, nor on the interaction between
      the sympathetic and parasympathetic systems in the heart.

PMID- 8746547
TI  - Maternal anxiety during pregnancy: effect on fetal behavior at 38 to 40 weeks of
      gestation.
AB  - The purpose of this study was to determine if there is a relationship between
      fetal behavior and maternal anxiety during pregnancy. The study population
      consisted of 18 uncomplicated human pregnancies at 38 to 40 weeks gestation.
      Maternal anxiety was assessed one time using Spielberger's State-Trait Anxiety
      Inventory. After an overnight fast, each mother was given a standard meal on
      arrival to the fetal testing unit. Each fetus was examined for 4 hours using
      heart rate monitoring and real-time sonography. Fetal behavioral states were
      assigned based on heart rate pattern and the presence or absence of eye and gross
      body movements. We found that, compared with fetuses of mothers with low trait
      anxiety scores, fetuses of mothers with relatively high trait anxiety scores
      spent significantly more time in quiet sleep and exhibited less gross body
      movement when in active sleep. The results of this pilot study raise the
      possibility that maternal anxiety during pregnancy may have a significant effect
      on fetal behavior.

PMID- 8746548
TI  - Admission to a neonatal intensive care unit as a predictor of long-term health: a
      12-year follow-up.
AB  - Long-term physical, emotional, and social health of neonatal intensive care unit
      (NICU) graduates was assessed. Twelve-year follow-up interviews were conducted
      with 253 (86.3%) mothers from a cohort interviewed after their child's birth. One
      hundred and sixteen children had been admitted to the NICU and 137 to the normal
      neonatal nursery (NNN) at a tertiary care hospital (1978 to 1980). NICU boys have
      more chronic physical health problems and have been hospitalized more often than
      NNN boys. A larger proportion of NICU boys have a physical impairment. NICU girls
      have lower social competence, social support, and self-esteem than NNN girls, and
      the impact of NICU admission on these outcomes was significantly greater for
      girls than boys. Long-term follow-ups should not be limited to very low birth
      weight infants. NICU admission could be a simple flag for primary care providers
      to identify children at risk for problems in adolescence, especially psychosocial
      problems among girls. Physical and emotional health should continue to be
      monitored into adolescence for all NICU graduates.

PMID- 8746549
TI  - Neurocognitive characteristics of individuals with resistance to thyroid hormone:
      comparisons with individuals with attention-deficit hyperactivity disorder.
AB  - Previous studies have demonstrated an association between resistance to thyroid
      hormone (RTH) and attention-deficit hyperactivity disorder (ADHD). To determine
      if the neurocognitive characteristics in individuals with RTH are similar to
      those observed in ADHD, 12 children with RTH from 7 families were matched to 12
      children with ADHD without RTH. Subjects were administered standardized
      intellectual, developmental, and school achievement tests. Parent and teacher
      ratings of children's hyperactivity and attention were similar for both groups,
      as were measures of attention, impulsivity, and verbal IQ. Children with RTH
      displayed lower nonverbal intelligence (performance IQ = 85) and academic
      achievement (> 1-2 SD below the mean) when compared with those with ADHD only
      (performance IQ = 99; achievement within 2 SD). Although children with RTH have
      behavioral characteristics similar to those with ADHD, their significantly weaker
      abilities of perceptual-organization and lower school achievement suggest a more
      severe neurobehavioral impairment than ADHD.

PMID- 8746550
TI  - Psychological distress in mothers of preterm infants.
AB  - The purpose of this study was to identify infant and maternal characteristics
      that predict psychological distress among mothers of preterm infants admitted to
      the neonatal intensive care unit (NICU). Infant characteristics included birth
      weight, gestational age, and ventilatory support, and maternal characteristics
      included age, parity, and socioeconomic status. Mothers (n = 142) completed
      questionnaires including a demographic form, the Parental Stressor Scale, and the
      Symptom Checklist 90-R. In hierarchical regression analyses, maternal NICU
      specific distress was more strongly predicted by infant characteristics [F(3,135)
      = 6.80, p < .05] with maternal variables covaried. Maternal general psychological
      distress was more strongly predicted by maternal characteristics [F(3,135) =
      6.05, p < .05]) with infant variables covaried. Twenty-eight percent of mothers
      reported clinically significant psychological distress compared with 10% in a
      normative population. Psychological distress among mothers of preterm infants
      appears to be common and deserves clinical consideration. The use of standardized
      questionnaires as part of the assessment process may improve case identification
      and psychosocial service delivery in the NICU.

PMID- 8746551
TI  - The developmental implications of prenatal and/or postnatal crack cocaine
      exposure in preschool children: a preliminary report.
AB  - Previous studies examining the development of prenatally cocaine-exposed children
      through 3 years of age have found no significant differences between exposed and
      control groups. This study explored the developmental correlates of prenatal
      and/or postnatal crack cocaine exposure in children between 4 and 6 years of age.
      Three groups were studied: Group 1, 18 prenatally-exposed children whose mothers
      continue to use crack; Group II, 28 children without prenatal exposure whose
      mothers presently use crack; and Group III, 28 children whose mothers never used
      crack. Mothers were street-recruited and were comparable in race and
      socioeconomic status. The three groups of children did not differ on neurological
      gross motor and expressive language measures. However, prenatally exposed
      children performed significantly worse than others on receptive language and
      visual motor drawing tests. Prenatal crack exposure predicted poor visual motor
      performance even after control for intrauterine alcohol and marijuana exposure,
      age, birth weight, and duration of maternal crack use.

PMID- 8746554
TI  - The American war zone: what children can tell us about living with violence.

PMID- 8746555
TI  - Pathogenesis, prevention, and treatment of neuroleptic-induced movement
      disorders.

PMID- 8746556
TI  - Drug discrimination: no evidence for tolerance to opiates.

PMID- 8746557
TI  - Gastrointestinal prokinetic benzamides: the pharmacology underlying stimulation
      of motility.

PMID- 8746558
TI  - Pancreatic expression of B7 co-stimulatory molecules in the non-obese diabetic
      mouse.
AB  - Expression of the co-stimulatory molecule B7-1 (CD80) on pancreatic beta cells
      can overcome peripheral T cell tolerance in transgenic models of autoimmune
      disease. This study aimed to determine if aberrant B7-1 or B7-2 (CD86) expression
      on pancreatic beta cells is involved in the pathogenesis of autoimmune diabetes
      in non-obese diabetic (NOD) mice. Immunohistochemical analysis of NOD pancreas
      sections revealed no evidence of B7-1 or B7-2 expression on pancreatic beta cells
      at any stage prior to the onset of either spontaneously arising or
      cyclophosphamide-accelerated diabetes. Likewise, the NOD-derived NIT-1 beta cell
      line did not express surface B7 or B7-1 mRNA either constitutively or following
      exposure to IFN-gamma and TNF-alpha, two cytokines known to be present in the
      insulitis lesion of NOD mice, or cAMP which can induce B7-1 expression on B
      cells. Both B7-1 and B7-2 were, however, highly expressed on the majority of
      islet-infiltrating inflammatory cells in NOD mice between days 7 and 12 after the
      administration of cyclophosphamide which results in accelerated beta cell
      destruction. Likewise B7-1 and B7-2 were extensively expressed on islet
      infiltrating cells present at the time of diabetes onset in NOD SCID mice with
      adoptively transferred diabetes. By immunohistochemistry and flow cytometry, it
      was determined that the phenotype of B7+ cells in the pancreas of NOD mice 9 days
      after cyclophosphamide included a mixture of macrophages and both CD4+ and CD8+ T
      cells. B7-2 was also expressed on islet-infiltrating cells in the spontaneously
      occurring diabetes of female NOD mice, but the levels of B7-1 expression were low
      in comparison with the accelerated models of diabetes. RIP-IL-2 transgenic mice,
      which have extensive islet infiltration but no autoimmune beta cell destruction,
      also had virtually no B7-1 expression and a minority of B7-2-expressing
      inflammatory cells. Thus, the activation of beta cell-specific T cells in NOD
      mice does not appear to be a result of aberrant expression of B7 on the beta
      cells. Expression of B7-1 and B7-2 on islet-infiltrating cells is, however,
      associated with autoimmune beta cell destruction, suggesting a role for the B7
      CD28 interaction in this process.

PMID- 8746559
TI  - Neonatal impaired response to viral superantigen encoded by MMTV(SW) and Mtv-7.
AB  - MMTV(SW) is an exogenous mouse mammary tumor virus that codes for a superantigen
      sharing the same V beta specificity as Mtv-7 (Mis-1a). Neonatal mice infected by
      suckling-infected milk show a deletion of the CD4+ V beta 6+ T cell subset within
      8 weeks. In contrast, adult mice infected by injection of the virus in the
      footpad have a much faster deletion, which occurs within 2 weeks. In the present
      work, we investigated possible mechanisms for the different kinetics of deletion
      in the adult and newborn mice. To find out if the route of infection could be
      responsible for this discrepancy, we infected 5-day-old and adult mice by
      injection in the footpad. Our results demonstrate that the route of infection is
      not responsible for the delayed kinetics of reactive T cell deletion since
      newborn mice injected with the virus show similar kinetics to neonates infected
      by maternal milk. To exclude differences in viral spreading between the two
      models, we used a PCR assay to detect proviral DNA. Spreading of the virus was
      shown to occur at a similar rate or even more rapidly in neonates than in adults.
      We also compared the activation induced by MMTV(SW) or Mis-1a spleen cells in the
      draining lymph node in neonatal and adult mice and showed that a poor local
      activation is induced in neonates compared with adults. In vitro, neonatal T cell
      reactivity to anti-V beta 6 antibody was also impaired. Thus, the delay in clonal
      deletion could be linked to impaired expression, presentation and/or response to
      the viral superantigen. Our results suggest that the initial response to MMTV(SW)
      could be of importance for the kinetics of reactive T cell deletion.

PMID- 8746560
TI  - Homing of lymphocytes into islets of Langerhans in prediabetic non-obese diabetic
      mice is not restricted to autoreactive T cells.
AB  - Non-obese diabetic mice spontaneously develop a type 1 diabetes. The entry of
      leukocytes in the islets of Langerhans was studied in untreated and in irradiated
      mice. FITC-labeled cells from spleen, lymph nodes or bone marrow of healthy or
      diabetic donors did home to the inflamed islets of unmanipulated recipients. B
      and T cells migrated equally well, whereas rare neutrophils entered the islets.
      Lymphocyte homing was blocked by anti-L-selectin and anti-alpha 4 integrin
      antibodies. Insulitis transfer experiments using mice congenic at the Thy-1 locus
      showed that anti-alpha 4 integrin treatment totally inhibited the migration of
      donor type T cells in the islets, whereas anti-L-selectin only had an early and
      transient effect. The expression of vascular addressins in the islets was linked
      to the presence of mononuclear cells. Thus, in the developing islet infiltrate,
      the entry of cells appears continuous and restricted to lymphocytes, whether
      autoreactive or not, and involves the L-selectin. This mechanism rather promotes
      the migration of naive-type cells. Conversely, during the adoptive transfer of
      insulitis the entry of L-selectin- diabetogenic T cells is highly favored, to the
      detriment of L-selectin+ naive type cells.

PMID- 8746561
TI  - Induction of sterile transcription from the kappa L chain gene locus in V(D)J
      recombinase-deficient progenitor B cells.
AB  - B cell development in RAG-2-deficient (RAG-2T) mice is impeded at an early stage,
      due to the inability of these animals to rearrange their endogenous ig gene loci.
      Expression of an E mu-bcl-2 transgene in these mice did not change this
      phenotype. However, stromal cell/IL-7-reactive B cell progenitors (pro-B cells)
      were found in fetal live and bone marrow of RAG-2T and RAG-2T/E mu-bcl-2
      transgenic mice in numbers comparable to normal mice. Like cells from normal mice
      they are c-kit+, surrogate L chain+ and CD25-, and can proliferate in vitro for
      long periods of time. Upon IL-7 deprivation, they can be induced to differentiate
      into c-kit-, surrogate L chain- and CD25+ cells that are no longer clonable on
      stromal cells and IL-7. Furthermore, sterile transcription from the kappa L chain
      gene loci is induced. The latter was also observed with pro-B cells directly
      isolated ex vivo from the bone marrow of RAG-2-deficient animals. The results
      suggest that progenitor B cell differentiation can occur in cells from V(D)J
      recombinase-deficient mice to the stage where kL chain gene rearrangements would
      normally be initiated. It further indicates that some molecular programs of early
      B cell differentiation can take place in the absence of Ig gene rearrangements.

PMID- 8746562
TI  - DR alpha: E beta heterodimers in DRA transgenic mice hinder expression of E
      alpha: E beta molecules and are more efficient in antigen presentation.
AB  - HLA-DRA transgenic (tg) mice on H-2d background were constructed to study
      assembly, expression and function of DR alpha: E beta class II heterodimers when
      an alternate E alpha chain is available. Cytofluorimetric analysis and
      immunoprecipitation studies demonstrate that the majority (90%) of E beta d
      molecules on class II-positive splenocytes from DRA-tg mice are associated with
      DR alpha rather than E alpha chains. To characterize the functional role of the
      interspecies as compared with the wild-type I-E molecules, MHC restriction and T
      cell epitope immunodominance of synthetic peptides spanning the entire sequence
      of 65 kDa heat shock protein (hsp) from Mycobacterium tuberculosis were
      determined in hsp-primed DRA-tg and DBA/2 mice. A similar pattern of
      responsiveness was observed in both strains, but hsp epitopes recalled a higher
      response in DRA-tg as compared with DBA/2 mice. A panel of T cell hybridomas
      specific for two hsp peptides or a hen egg white lysozyme peptide presented by
      both DR alpha: E beta d and E alpha d: E beta d was studied in detail.
      Surprisingly, DR alpha: E beta d dimers present these peptides more efficiently
      than E alpha d: E beta d, even when the TCR was selected in mice expressing only
      E alpha d: E beta d molecules. The higher efficiency of antigen presentation by
      DR alpha: E beta d dimers does not appear to depend on increased binding affinity
      for peptides, as demonstrated by competition for antigen presentation, nor on
      increased efficiency in the interaction with CD4 molecules. Rather, the higher
      efficiency of antigen presentation could be explained by a more effective ligand
      TCR interaction. This is consistent with molecular modeling based on the class II
      structure, indicating that 16 out of 17 substitutions between the first domain of
      E alpha d and DR alpha chains ile outside the peptide binding groove and are
      potentially available for interaction with the TCR.

PMID- 8746563
TI  - Thy-1 induced on rat endothelium regulates vascular permeability at sites of
      inflammation.
AB  - We investigated the role of surface adhesion molecules on endothelial cells in
      regulating vascular permeability, in vitro and in vivo. Cultured rat endothelial
      cells (REC) express Thy-1, intercellular adhesion molecule-1 (ICAM-1), CD44 and
      RT1A. Permeability of albumin across the REC monolayer increased through the
      interaction of Thy-1 and anti-Thy-1 mAb, but not through ICAM-1 and anti-ICAM-1,
      CD44 and anti-CD44, and RT1A and anti-RT1A mAb. This anti-Thy-1-effect was
      completely inhibited when the calmodulin antagonist W-7 and the protein kinase
      inhibitor H-7 was combined, while the IL-6-mediated increase in REC permeability
      was blocked by either W-7 or H-7, independently. The anti-Thy-1-mediated
      permeability increase was additively augmented when IL-6 was admixed. These data
      suggest that intracellular signaling pathways of anti-Thy-1- and IL-6-mediated
      permeability regulation may be overlapping to some extent but are largely
      independent. As anti-Thy-1-treatment generated rearrangement of vimentin
      filaments within REC, alteration of the cytoskeleton distribution may possibly
      correlate with the regulation of permeability. Although Thy-1-expression on rat
      vascular endothelium in vivo was not evident, it was induced at sites of Freund's
      complete adjuvant-induced dermatitis. The administered anti-Thy-1 mAb exclusively
      located on vascular endothelial surface at the sites of inflammation. Vascular
      permeability in inflamed skin tissues was significantly augmented when anti-Thy-1
      but not anti-ICAM-1, anti-CD44 or anti-RT1A mAb was administered i.v., without
      affecting populations of inflammatory cells. The collective evidence suggests
      that Thy-1 induced on rat endothelium is one important regulatory event in
      vascular permeability at sites of inflammation.

PMID- 8746564
TI  - Expression of Fas in B cells of the mouse germinal center and Fas-dependent
      killing of activated B cells.
AB  - Fas is a cell-surface protein of 45 kDa. Binding of the Fas ligand (FasL) to Fas
      induces apoptosis in Fas-bearing cells. Analysis of mouse mutants in either Fas
      or FasL have indicated that the Fas system is involved in apoptosis of
      lymphocytes. To identify the cells expressing Fas, mouse spleen sections were
      analyzed by in situ hybridization and immunohistochemistry. Fas mRNA was detected
      in the T cells of the inner region of the periarterial lymphatic sheath and the
      inner lumen of the marginal zone. The cells in the outer region of the
      periarterial lymphatic sheath weakly expressed Fas mRNA, whereas it was abundant
      in the B cells of germinal centers. Immunizing mice with keyhole limpet
      hemocyanin induced formation of many germinal centers in the spleen. The B cells
      in the activated germinal center expressed abundant Fas and underwent apoptosis.
      The in vitro activation of splenocytes with lipopolysaccharide induced Fas
      expression in B cells and the B cells became sensitive to the Fas-mediated
      apoptosis. These results suggest that Fas is involved in the activation-induced
      death of B cells.

PMID- 8746565
TI  - Natural ligand motifs of H-2E molecules are allele specific and illustrate
      homology to HLA-DR molecules.
AB  - Motifs of peptides naturally associated with H-2Ek and Ed molecules were
      determined by (I) pool sequencing of natural ligand mixtures and (II) sequencing
      of individual natural ligands followed by their alignment to the basic motif
      suggested by pool sequencing. The data reveal nine amino acid motifs with
      interaction sites at relative positions P1, P4, P6 and P9, with specificities
      that are identical at some but different at other anchor positions between Ed and
      Ek motifs, illustrating the different requirements for peptides to be presented
      by these two MHC molecules. The anchors with the most restricted specificity are
      P1 and P9. P1 is aliphatic for Ek and predominantly aromatic for Ed. P9 is
      positively charged for both molecules. P4 and P6 show a totally different amino
      acid preference between Ek and Ed ligand motifs. An alignment of Ed and Ek
      protein sequences to the recently reported HLA-DR1 pocket residues is in
      agreement with observed anchor residues in Ek and Ed motifs, thus confirming the
      predicted similarity of mouse class II E molecules with human DR molecules.
      Furthermore, this alignment was extended to the putative pockets of class II Eb
      and Ek molecules, and allowed, together with sequence information of previously
      identified natural ligands of Eb and Ec molecules, a prediction of their
      respective motifs. The information obtained by this study should be useful to
      identify putative class II E epitopes in proteins and to design peptides for
      blocking class II E molecules.

PMID- 8746566
TI  - Mapping of the linear site on the Fas/APO-1 molecule targeted by the prototypic
      anti-Fas mAb.
AB  - Fas/APO-1 is a member of the nerve growth factor/tumor necrosis factor (TNF)
      family of receptors and has been shown to mediate apoptotic cell death upon
      binding of specific mAb. We report here that the prototypic anti-human Fas mAb
      (clone CH-11) induces apoptosis by binding to a linear epitope present on the
      extracellular domain of the Fas/APO-1 protein. Synthetic peptides corresponding
      to this epitope blocked the apoptotic effect of the antibody in a susceptible
      Jurkat T cell line. Based upon the similarity between the Fas/APO-1 protein and
      the recently crystallized soluble TNF receptor type I, we generated a molecular
      model of Fas/APO-1, Our computer modeling indicates that the antibody binding
      region forms a hairpin loop on the surface of the Fas/ APO-1 protein. These
      findings further our understanding of the Fas/APO-1-mediated apoptotic signal and
      may provide a useful tool in future investigations of programmed cell death.

PMID- 8746567
TI  - Disrupted development of thymocytes expressing a transgenic TCR upon CD4
      overexpression.
AB  - CD4 assists in T cell recognition of peptides bound to MHC class II molecules by
      binding to a non-polymorphic region on class II and stabilizing TCR recognition
      of the peptide-class II complex. Overexpression of CD4 in transgenic mice
      expressing a class II-restricted TCR resulted in a dramatic loss of thymocytes
      that became evident soon after the TCR and CD4 were co-expressed. Both the thymus
      and lymph nodes of the double-transgenic mice had reduced numbers of CD4 lineage
      T cells. A large proportion of the remaining CD4 lineage T cells lost either the
      transgenic TCR alpha or beta chains. The double-transgenic mice continued to
      generate thymocytes and T cells that expressed the transgenic TCR, but these
      cells did not express endogenous CD4. Overexpression of CD4 thus severely
      disrupts the normal developmental pathway of these thymocytes, supporting a model
      in which avidity of the TCR complex for self class II molecules determines the
      outcome of thymocyte development.

PMID- 8746568
TI  - Maturation of neonatal human CD4 T cells: III. Role of B7 co-stimulation at
      priming.
AB  - We previously reported that human naive CD4 T cells differentiate into effector
      cells producing type 1 (IL-2, IFN-gamma) and type 2 (IL-4, IL-5, IL-10) cytokines
      after priming with anti-CD3 mAb presented on irradiated CD32-transfected mouse L
      fibroblasts, in the absence of exogenous cytokine. Here we first show that the
      CD32 L fibroblasts act not only by cross-linking anti-CD3 mAb but also by
      providing a B7-mediated co-stimulation signal which is required for the
      activation of naive T cells. Using a selected anti-CD3 mAb (64.1) we next
      demonstrate that colligation of CD3 and CD28 with soluble mAb is sufficient to
      activate highly purified naive CD4 T cells for proliferation, IL-4 mRNA
      expression, IL-4 secretion, and maturation into IL-4- and IL-5-producing cells.
      Finally, we show that the intensity of B7 co-stimulation at priming markedly
      affects the lymphokine-producing phenotype of primed cells. Indeed, cells primed
      on CD32-B7 double L transfectants produce much more IL-4 and IL-5 and slightly
      less IFN-gamma than those primed on CD32 L cells. The enhanced IL-4/IL-5
      producing capacity of cells primed on CD32-B7 L fibroblasts may be related to
      increased IL-4 production during priming. It is suggested that the maturation of
      naive T cells along the Th2 or Th1 pathway may be regulated by the level of B7
      expressed on APC.

PMID- 8746569
TI  - Promotion of V(D)J recombinational accessibility by the intronic E kappa element:
      role of the kappa B motif.
AB  - The accessibility of a chromosomally integrated TCR beta minilocus recombination
      substrate in a V(D)J recombinase-inducible cell line (HDR37) depends on
      incorporation of transcriptional enhancer elements such as the Ig kappa light
      chain intronic enhancer (E kappa). The E kappa element contains several
      functional motifs including the kappa B motif, which binds the NF-kappa B
      transcription factor. To assess molecular mechanisms by which E kappa promotes
      V(D)J recombinational accessibility, we compared the abilities of the wild-type E
      kappa, a corresponding E kappa sequence with a mutant kappa B motif (E kappa
      kappa B-) and a kappa B motif dimer (kappa B2) to function in the context of the
      TCR beta minilocus/HDR37 system. The E kappa-containing minilocus underwent
      demethylation, transcription and V(D)J recombination, independently of copy
      number of integration site. Transfectants containing low copy numbers (one or
      two) of the E kappa-kappa B(-)-containing minilocus, like enhancerless or kappa
      B2-containing miniloci at any copy number, were inactive with respect to all
      three processes. In contrast, high-copy-number integrants of the E kappa-kappa B-
      substrates showed an integration-site dependent activation of all three
      processes. Together these data show that the kappa B motif plays a critical role
      in the ability of E kappa to confer V(D)J recombinational accessibility, but that
      it is not sufficient to mediate this process by itself.

PMID- 8746570
TI  - If you want mediocre care, fail to reward people for giving excellent care.

PMID- 8746571
TI  - Indocyanine green angiography for recurrent choroidal neovascularization in age
      related macular degeneration.
AB  - BACKGROUND AND OBJECTIVE: Recurrence of choroidal neovascular membranes (CNV)
      occurs frequently following laser photocoagulation. Recurrent CNV can be
      difficult to treat because they may not be well defined by fluorescein
      angiography. PATIENTS AND METHODS: The fluorescein and indocyanine green (ICG)
      angiograms of 58 eyes of 57 patients who presented with clinically suspected
      recurrence were evaluated retrospectively. RESULTS: In 14 eyes (24%), a well
      defined recurrent CNV could be identified by evaluating the fluorescein
      angiogram. In 6 (14%) of the remaining 44 eyes, a well-defined recurrent CNV was
      identifiable by ICG angiography. CONCLUSION: A role for ICG angiography in the
      care of patients with suspected recurrent CNV is discussed.

PMID- 8746572
TI  - Ultrasound biomicroscopy and corneal endothelium in Nd:YAG-laser iridotomy.
AB  - BACKGROUND AND OBJECTIVE: Thirty eyes affected by angle-closure glaucoma that had
      undergone YAG-laser iridotomy were studied to evaluate variations of central
      anterior chamber depth, width of the angle, and loss of endothelial cells after
      laser treatment. PATIENTS AND METHODS: These parameters were determined before
      and after iridotomy: endothelial cell count using a "non-contact" specular
      biomicroscope, and anterior chamber depth and angle width using ultrasound
      biomicroscopy (UBM). The width of the iridotomy and the distance of the iridotomy
      from the scleral spur and from the corneal endothelium were also measured by UBM,
      after laser treatment. RESULTS: Results confirmed that, after iridotomy, there is
      not a significant variation in the central depth of the anterior chamber: it goes
      from 2.02 mm pre-laser to 2.07 +/- 0.38 mm post-laser. There is, however, a
      statistically significant increase in the angle (P < .001), which goes from 10.69
      +/- 8.88 degrees (0.109 +/- 0.07 mm) to 21.03 +/- 11.28 degrees (0.183 +/- 0.09
      mm). The mean dimension of the iridotomies was 0.46 +/- 0.13 mm. The mean
      endothelial cell count was 55.8 +/- 4.08 cells per linear millimeter before laser
      treatment and 47.01 +/- 5.39 cells per linear millimeter afterward (P <.001).
      CONCLUSION: This study confirms that YAG-laser iridotomy leads to a reduction in
      the average endothelial cell density. The loss of these cells is inversely
      proportional to the distance of the iridotomy from the endothelium and the
      scleral spur.

PMID- 8746573
TI  - Effects of wound architecture and suture technique on postoperative astigmatism.
AB  - BACKGROUND AND OBJECTIVE: A prospective randomized investigation was performed to
      evaluate the effects of wound architecture and suture techniques on postoperative
      astigmatism after phacoemulsification and intraocular lens implantation. PATIENTS
      AND METHODS: Two hundred eyes with preexisting with-the-rule astigmatism were
      randomized into four groups: (1) sutureless scleral tunnel frown incision, (2)
      scleral tunnel frown incision with a horizontal suture, (3) scleral tunnel frown
      incision with both a horizontal and a running suture, and (4) posterior limbal
      acute beveled cataract incision with a running suture. All the incisions were
      placed in the vertical steep meridian. RESULTS: Data were analyzed from 128 cases
      with 1-year follow-up. The results revealed that at the 2-month postoperative
      visit, preexisting astigmatism was significantly reduced in group 1 (P = .029)
      and significantly increased in groups 3 (P = .020) and 4 (P = .005). There was no
      significant change in group 2 (P = .06). By the 1-year postoperative visit, there
      was no significant difference in astigmatism from preoperative levels for all
      four groups. Vector analysis revealed no significant difference in the mean
      surgically induced cylinder at 1 year in all four groups. The number of eyes with
      induced against-the-rule astigmatism, however, was significantly higher than the
      number of eyes with induced with-the-rule astigmatism in all four groups (P
      <.01). CONCLUSION: The authors found that sutured wounds placed in the vertical
      steep meridian may initially increase with-the-rule astigmatism, whereas
      nonsutured wounds placed in the vertical steep meridian may initially reduce with
      the-rule astigmatism. By 1 year, however, a mean flattening of the vertical steep
      meridian was observed in the three groups with sutures as well as in the group
      without sutures.

PMID- 8746574
TI  - Clinical management of posterior chamber intraocular lens implants dislocated in
      the vitreous cavity.
AB  - BACKGROUND AND OBJECTIVE: To discuss the options for management and review the
      authors' experience with dislocated posterior chamber intraocular lens implants.
      PATIENTS AND METHODS: A retrospective review was performed over a 3-year period
      of 12 consecutive patients with posterior chamber intraocular lens (PC IOL)
      implants dislocated into the vitreous cavity. The patients were managed with pars
      plana vitrectomy, repositioning or exchange, and transscleral suture fixation of
      the PC IOL. RESULTS: The visual acuity was 20/50 or better in 9 patients and the
      transscleral suture fixated PC IOL was in good position in 12 patients at the
      most recent follow-up. Perioperative complications included corneal edema,
      cystoid macular edema, retinal breaks and detachments, and suture erosion.
      CONCLUSION: Visual and anatomic outcomes were favorable.

PMID- 8746575
TI  - Mortality and morbidity associated with ophthalmic surgery.
AB  - BACKGROUND AND OBJECTIVES: To study the mortality and morbidity among the
      patients undergoing ophthalmic surgery under local or general anesthesia.
      MATERIALS AND METHODS: A retrospective analysis of all patients who underwent
      ophthalmic surgery at Sankara Nethralaya, Madras, India, between 1979 and 1988,
      was performed. Relevant details included the preoperative medical status of the
      patients (ASA status), type of surgical procedure, type of anesthesia, and
      intraoperative and postoperative complications. RESULTS: The overall mortality
      rate was 1.15 per 1000. There was a decrease in the mortality rate from 2.09 per
      1000 in the first 5-year period to 0.37 per 1000 in the second 5-year period. The
      factors significantly associated with mortality were hypertension, presence of
      cardiac pacemaker, renal disease, duration of surgery, type of surgery, and
      physical status (American Society of Anaesthesiologists classification).
      CONCLUSION: Identifying the risk factors can help reduce the mortality in
      ophthalmic surgery.

PMID- 8746576
TI  - Ocular injuries related to air bag inflation.
AB  - BACKGROUND AND OBJECTIVES: The effectiveness of air bags as a safety device in
      decreasing fatalities and reducing morbidity in frontal impact motor vehicle
      accidents has been well established. However, case reports have surfaced
      documenting ocular injuries related to air bag inflation. The purpose of this
      study was to identify and analyze ocular injuries sustained during air bag
      inflation. PATIENTS AND METHODS: Hospital emergency room records were reviewed
      retrospectively for a period of 4 years for patients who had sustained ocular
      injuries in motor vehicle accidents. Those injuries associated with air bag
      inflation were analyzed as to the nature of the injury, type of vehicle, speed,
      and visual morbidity. RESULTS: Fourteen cases of ocular injury related to air bag
      inflation were identified. Hyphema (nine cases) and cornea abrasion (eight cases)
      were the most common. Three cases, all patients who had been wearing glasses,
      sustained serious and permanent ocular damage. CONCLUSION: While air bags are an
      unequivocal safety feature, ocular injuries do occur that are related to air bag
      inflation. Eyeglass wear may present an additional risk factor.

PMID- 8746578
TI  - The effect of trephination on corneal topography.
AB  - BACKGROUND AND OBJECTIVE: A prospective study was performed to assess the effect
      of trephination on corneal curvature. MATERIALS AND METHODS: Thirty-seven fresh
      porcine globes with intact corneal epithelium were used. Radius of curvature,
      central dioptric power, and powers and axes of the steepest and flattest
      meridians were obtained using a vertically mounted computerized videokeratography
      unit. Following 8-mm vacuum trephination of the central donor corneas, the said
      parameters were reassessed on the resultant buttons. No globes with epithelial
      defects were included in the study. RESULTS: The mean corneal radius of curvature
      (mm) increased from 8.68 +/- 0.79 to 10.46 +/- 3.24 (P = .005), the central
      dioptric power (D) decreased from 39.36 +/- 3.84 to 36.31 +/- 10.15 (P = .08),
      and the total corneal asphericity (D) increased from 5.03 +/- 2.99 to 7.47 +/-
      3.42 (P = .0001). No significant changes in the axes of the steepest and the
      flattest meridians were noted following trephination. CONCLUSION: Trephination
      leads to significant corneal flattening and increased asphericity. Corneal
      topography can be used successfully as a research tool for whole globes and
      trephined buttons.

PMID- 8746577
TI  - Laser photocoagulation using binocular indirect ophthalmoscope laser delivery
      systems.

PMID- 8746579
TI  - Complement-derived anaphylatoxins in human donor corneas treated with excimer
      laser.
AB  - BACKGROUND AND OBJECTIVE: An inflammatory response produced by excimer laser
      photorefractive keratectomy (PRK) may be associated with the subsequent corneal
      haze and regressions in refractive error observed after treatment. Complement
      derived anaphylatoxins, potent mediators of inflammation, may have a role in
      postoperative healing. MATERIALS AND METHODS: Twenty right human donor corneas
      underwent a 6-D excimer laser PRK treatment. The corresponding left donor corneas
      served as the controls. After incubation in tissue culture media for 6 hours and
      elution in phosphate-buffered saline with EDTA for 24 hours, complement-derived
      anaphylatoxins C3a, C4a, and C5a were measured in corneal eluates by
      radioimmunoassay. RESULTS: Compared with control corneas, the excimer PRK corneas
      failed to demonstrate a significant increase in C3a, C4a, or C5a levels (P >
      .05). CONCLUSIONS: These results suggest that the excimer laser at this dose does
      not activate significant complement in the cornea.

PMID- 8746580
TI  - Cracking of acrylic intraocular lenses during capsular bag insertion.

PMID- 8746581
TI  - Rupture of radial keratotomy sites after presumed blunt trauma.

PMID- 8746582
TI  - A technique to evaluate fluid flow in glaucoma shunts.

PMID- 8746583
TI  - A new method of holding the suture needle.

PMID- 8746584
TI  - Use of a personal computer to produce composite orbital images.

PMID- 8746585
TI  - Use of indocyanine green with diode laser transscleral cyclophotocoagulation in a
      cadaver eye model.

PMID- 8746586
TI  - Concurrent 5-fluorouracil, mitomycin C and irradiation in locally advanced cervix
      cancer.
AB  - We reviewed 177 patients treated with radical radiotherapy for locally advanced
      (FIGO stages IIB, IIIA, IIIB) cervix cancer between January 1979 and December
      1989. The radiotherapy was given by external beam treatment to the pelvis and by
      an intracavitary caesium insertion. Ninety-three patients also received
      chemotherapy which consisted of infusional 5-fluorouracil during the first and
      last weeks of the external beam component of the radiotherapy, combined with
      bolus mitomycin C (group A, 64 patients) or without mitomycin C (group B, 29
      patients). These groups were compared with patients treated by radiotherapy alone
      (group C, 84 patients). The median follow-up was 7.2 years. The median survival
      time for all patients was 47 months, but was significantly higher (87 months, p =
      0.004) for group A. Rates of relapse-free survival and local control were also
      higher in group A. Toxicity was assessed in detail using the Franco-Italian
      glossary. There was a relatively high rate of complications, particularly in
      group A, with 36% of patients having grade 3 or 4 complications. This increase in
      toxicity persisted through all follow-up time intervals. Patients in group B also
      demonstrated a higher rate of toxicity than group C, but this increase was
      limited to the first 6 months of follow-up. The use of mitomycin C in addition to
      radiotherapy and 5-fluorouracil should be regarded with caution, as other studies
      have also shown that toxicity is increased, but without improvements in survival.

PMID- 8746587
TI  - Radiotherapy with carbogen breathing and nicotinamide in head and neck cancer:
      feasibility and toxicity.
AB  - The feasibility and early toxicity of radiotherapy with carbogen breathing and
      nicotinamide was tested in 74 head and neck cancer patients. Forty patients with
      laryngeal and hypopharyngeal tumors were treated with an accelerated schedule
      combined with carbogen alone (16) or with carbogen and nicotinamide (24). Thirty
      four patients with far advanced unresectable tumors of the oral cavity and
      oropharynx received conventional radiotherapy with carbogen [16] or with carbogen
      and nicotinamide (18). Some enhancement of skin reaction was observed with
      nicotinamide but this remained well within limits of tolerance. With the
      accelerated regimen there was increased severity of mucosal damage expressed as
      confluent mucositis in 95% of patients which required healing times of 3-4 months
      in four patients. Eventually restoration of the mucosal lining was complete in
      all cases. Nausea and vomiting are the most frequent side effects of nicotinamide
      and were reported by 60% and 36% of the subjects, respectively. In 26% this was
      reason to discontinue drug intake. Severe renal dysfunction was associated with
      nicotinamide intake in two patients of this study and in one other patient who
      presented later. It is our conclusion that radiotherapy combined with carbogen
      and nicotinamide is a safe treatment with manageable side effects. We recommend
      not to give nicotinamide concomitantly with nephrotoxic medication or to patients
      who have impaired renal function. Preliminary tumor control rates are encouraging
      and clinical testing will be continued.

PMID- 8746588
TI  - The accuracy of CT-based inhomogeneity corrections and in vivo dosimetry for the
      treatment of lung cancer.
AB  - PURPOSE: To determine the accuracy of dose calculations based on CT-densities for
      lung cancer patients irradiated with an anterio posterior parallel-opposed
      treatment technique and to evaluate, for this technique, the use of diodes and an
      Electronic Portal Imaging Device (EPID) for absolute exit dose and relative
      transmission dose verification, respectively. MATERIALS AND METHODS: Dose
      calculations were performed using a 3-dimensional treatment planning system,
      using CT-densities or assuming the patient to be water-equivalent. A simple
      inhomogeneity correction model was used to take CT-densities into account. For 22
      patients, entrance and exit dose calculations at the central beam axis and at
      several off-axis positions were compared with diode measurements. For 12
      patients, diode exit dose measurements and exit dose calculations were compared
      with EPID transmission dose values. RESULTS: Using water-equivalent calculations,
      the actual exit dose value under lung was, on average, underestimated by 30%,
      with an overall spread of 10% (1 SD) in the ratio of measurement and calculation.
      Using inhomogeneity corrections, the exit dose was, on average, overestimated by
      4%, with an overall spread of 6% (1 SD). Only 2% of the average deviation was due
      to the inhomogeneity correction model. The other 2% resulted from a small
      inaccuracy in beam fit parameters and the fact that lack of backscatter is not
      taken into account by the calculation model. Organ motion, resulting from the
      ventilatory or cardiac cycle, caused an estimated uncertainty in calculated exit
      dose of 2.5% (1 SD). The most important reason for the large overall spread was,
      however, the inaccuracy involved in point measurements, of about 4% (1 SD), which
      resulted from the systematic and random deviation in patient set-up and therefore
      in the diode position with respect to patient anatomy. Transmission and exit dose
      values agreed with an average difference of 1.1%. Transmission dose profiles also
      showed good agreement with calculated exit dose profiles. CONCLUSIONS: The study
      shows that, for this treatment technique, the dose in the thorax region is quite
      accurately predicted using CT-based dose calculations and a simple heterogeneity
      correction model. Point detectors such as diodes are not suitable for exit dose
      verification in regions with inhomogeneities. The EPID has the advantage that the
      dose can be measured in the entire irradiation field, thus allowing an accurate
      verification of the dose delivered to regions with large dose gradients.

PMID- 8746589
TI  - The optimisation of wedge filters in radiotherapy of the prostate.
AB  - A treatment plan optimisation algorithm has been applied to 12 patients with
      early prostate cancer in order to determine the optimum beam-weights and wedge
      angles for a standard conformal three-field treatment technique. The optimisation
      algorithm was based on fast-stimulated-annealing using a cost function designed
      to achieve a uniform dose in the planning-target-volume (PTV) and to minimise the
      integral doses to the organs-at-risk. The algorithm has been applied to standard
      conformal three-field plans created by an experienced human planner, and run in
      three PLAN MODES: (1) where the wedge angles were fixed by the human planner and
      only the beam-weights were optimised; (2) where both the wedge angles and beam
      weights were optimised; and (3) where both the wedge angles and beam-weights were
      optimised and a non-uniform dose was prescribed to the PTV. In the latter PLAN
      MODE, a uniform 100% dose was prescribed to all of the PTV except for that region
      that overlaps with the rectum where a lower (e.g., 90%) dose was prescribed. The
      resulting optimised plans have been compared with those of the human planner who
      found beam-weights by conventional forward planning techniques. Plans were
      compared on the basis of dose statistics, normal-tissue-complication-probability
      (NTCP) and tumour-control-probability (TCP). The results of the comparison showed
      that all three PLAN MODES produced plans with slightly higher TCP for the same
      rectal NTCP, than the human planner. The best results were observed for PLAN MODE
      3, where an average increase in TCP of 0.73% (+/- 0.20, 95% confidence interval)
      was predicted by the biological models. This increase arises from a beneficial
      dose gradient which is produced across the tumour. Although the TCP gain is small
      it comes with no increase in treatment complexity, and could translate into
      increased cures given the large numbers of patients being referred. A study of
      the beam-weights and wedge angles chosen by the optimisation algorithm revealed
      significant inter-patient variability the implications of which are examined.
      Probably the most significant benefit of the algorithm is the time saved (about a
      factor of 10) in computing optimised beam-weights and wedge angles for this
      simple plan.

PMID- 8746590
TI  - Comparison of imaging accuracy at different MRI units based on phantom
      measurements.
AB  - In this investigation standardized on-site phantom measurements at 27 MRI units
      were carried out. A scoring system was developed for rating both symmetry and
      distortion of the image. This study shows, with regard to the clinical use of MRI
      assisted treatment planning in radiotherapy, that in more than 85% of all planes
      (transversal, sagittal, coronal) the MRI units were equivalent to the standard
      known from literature.

PMID- 8746591
TI  - Changes to dose in the build-up region when using multi-leaf collimators in place
      of lead blocks supported on an accessory tray.
AB  - Doses in the build-up region have been compared for regular fields with and
      without a perspex accessory tray and for two irregular fields defined by either a
      Philips multi-leaf collimator (MLC) or lead blocks. The results show an increase
      in doses within the build-up region, by up to a factor of two, primarily due to
      the presence of the accessory tray. Fields shaped with the MLC exhibited build-up
      characteristics similar to those in unblocked fields and hence there will be
      systematic changes to the build-up dose when treatments are transferred from lead
      blocking techniques to those using an MLC mounted within the treatment head.

PMID- 8746592
TI  - Repopulation response of mouse oral mucosa during unconventional radiotherapy
      protocols.
AB  - Repopulation in mouse tongue epithelium was determined during unconventional
      fractionation schedules, i.e., hyperfractionation (2 x 1.5 and 2 x 1.75 Gy/day)
      and accelerated treatment (2 x 3 Gy/day). The residual tolerance of the
      epithelium at defined days of the fractionated treatment was tested by graded
      single test doses (top-up design). The dose required to induce complete
      epithelial denudation in 50% of the animals (ED50) was used to calculate the
      number of fractions repopulated during the preceding treatment. After the first
      week of hyperfractionation, tolerance was reduced compared to untreated
      epithelium. However, subsequently no further change was observed, indicating
      complete compensation of the weekly dose with all doses per fraction used.
      Epithelial cell density, defined by histological examination in additional
      experiments, in all fractionation arms decreased similarly by approximately 40%
      during the first week and remained constant at 60-80% in the subsequent 2 weeks.
      During accelerated fractionation, the residual mucosal tolerance decreased
      continuously with treatment time and resulted in epithelial denudation after 12
      fractions. However, a substantial repopulation effect was observed, compensating
      1.5 fractions by day 2, and 5 fractions by day 5, respectively. After cessation
      of the therapy the repopulation rate clearly decelerated to compensate a dose
      equivalent to about 0.5 fractions per day. Cell density decreased linearly during
      the treatment with 5, 10 or 12 fractions at a rate close to normal cell loss.
      Marked cell production, dependent on the total fractionated dose, was seen from
      one day after the last fraction in each experimental arm. These results indicate
      that maximum stem cell repopulation occurs predominantly during treatment, while
      major production of differentiating cells take place in treatment splits.

PMID- 8746593
TI  - A single session of intraluminal brachytherapy in palliation of oesophageal
      cancer.
AB  - Between September 1987 and September 1993, 88 patients with oesophageal cancer
      were treated by a single session of intraluminal brachytherapy of 15 Gy
      prescribed at 1 cm distance from the central axis, using MDR137Cs (n = 51) during
      the first part of the study and HDR192Ir (n = 37) during the second part of the
      study. All patients were regarded as inoperable. Improvement of dysphagia,
      assessed 4-6 weeks after treatment, was noted in 50 of 75 (67%) evaluable
      patients, whereas swallowing ability was completely restored in 47% of them.
      Relapse of dysphagia occurred in 28 (37%) patients during follow-up. Additional
      palliative treatment consisted of endoprosthesis in 14 (19%), a second course of
      brachytherapy in 13 (17%), one or more dilatations only in 11 (15%) and laser
      treatment in four (5%) patients. One non-fatal haemorrhage and five fistulae
      occurred, all in the presence of tumour. Two severe ulcerations without evidence
      of tumour were noted, both managed by combined curative treatment. The median
      survival of the group investigated was 5.5 months. An exophytic, non-circular
      growth pattern was associated with a better response. In a multivariate analysis
      the presence of distant metastases (p = 0.0028), weight loss (p = 0.0051) and an
      exophytic growth pattern (p = 0.0199) were associated with a worse survival. The
      present data indicate that a single session of ILB is appropriate in the
      palliation of dysphagia in patients with inoperable oesophagal cancer showing bad
      prognostic signs. Up to now there has been no clear evidence for benefit of
      addition of ERT.

PMID- 8746594
TI  - The role of electronic portal imaging in tangential breast irradiation: a
      prospective study.
AB  - Side effects due to irradiation of normal tissues and local failure can be
      associated with deviations in the patient positioning in radiation therapy. In
      particular, tangential breast irradiation may include normal lung tissue or even
      a small portion of the heart in the field. A prospective study was performed to
      assess the precision and the reproducibility of the tangential breast irradiation
      technique with the help of on-line electronic portal imaging devices (EPID). The
      influence of respiration on the treatment set-up was evaluated. Also, a
      comparison was made with simulation films to study the degree of concordance with
      the intended treatment. Twenty patients with early breast cancer receiving post
      operative radiotherapy were entered in the study. Geometrical parameters were
      measured from daily on-line portal images taken for approximately 17 fractions of
      each tangential fields. Multiple images were also acquired (six per field) for
      six fractions for all patients, yielding a total of 2120 images including the
      simulator films. Random and systematic errors were obtained. Variations of the
      parameters between various fractions and within the same fraction were about 3 mm
      (1 SD) or less. Variation between simulation and treatment set-up was 4.3 mm or
      less. Large maximum deviations, reaching 22.9 mm, were observed in rare cases.
      This confirms the need to implement daily verification procedures and to correct
      deviations in the treatment set-up. The study has shown that EPID can help
      reaching a high accuracy in patient treatment.

PMID- 8746595
TI  - A proven and highly cost-effective method of early detection of breast cancer for
      developing countries.
AB  - Carcinoma of the breast is the third most common cancer in Indian women. With
      rapid industrialization and effective control of communicable diseases, better
      diagnostic and treatment facilities, cancer is emerging as a major health
      problem. Since early detection is the only way to reduce morbidity and mortality
      from breast cancer, we undertook a pilot project to evaluate efficacy of using
      existing manpower and resources for screening women in the high risk group.
      Methodology pros and cons, results, and recommendations are presented. Our method
      can be adopted by any developing country interested in a screening programme for
      malignant disease.

PMID- 8746596
TI  - A new patient positioning system using magnetic implants and magnetic field
      sensors.

PMID- 8746597
TI  - Three cases of breast angiosarcomas after breast-conserving treatment for
      carcinoma.

PMID- 8746598
TI  - Management of coexisting risk factors in hypertension--safe and sound?

PMID- 8746599
TI  - Diabetes and hypertension: prognostic and therapeutic considerations.
AB  - Hypertension and diabetes are common disorders which frequently co-exist. Both
      are risk factors for atherosclerotic vascular disease and their combination is
      associated with an increased incidence of nephropathy, ischaemic heart disease,
      peripheral vascular disease, and stroke. Several trials such as the HDFP and SHEP
      studies that included diabetic patients have demonstrated the beneficial effects
      of antihypertensive therapy in reducing mortality. In diabetes, studies have
      focussed predominantly on the efficacy of antihypertensive therapy in reducing
      the progression of diabetic kidney disease. Such therapy has been shown to
      decrease albuminuria in the setting of "normal" and elevated blood pressure in
      both type I and type II diabetic patients. This reduction in albuminuria has been
      observed in microalbuminuric diabetic patients and also in those with overt renal
      disease. Recent studies in type I diabetic patients with overt nephropathy
      indicate that these effects on urinary albumin excretion are associated with
      reduction in the rate of decline in renal function and development of end-stage
      renal failure. Indeed, several groups have shown that the initiation of
      antihypertensive therapy improves the prognosis of type I diabetic patients with
      nephropathy. While certain classes of drugs may reduce the rate of progression of
      complications such as nephropathy, others have side effect profiles that are
      disadvantageous in patients with diabetes.

PMID- 8746600
TI  - Severe hypertension with lone bilateral papilloedema: a variant of malignant
      hypertension.
AB  - Patients with severe hypertension with retinoscopic bilateral papilloedema only
      are not classically regarded as having malignant hypertension (MHT). We have
      encountered 23 such patients between 1965-1993, whilst over a similar period we
      have seen 315 patients who fulfilled the conventional criteria for MHT with
      bilateral retinal haemorrhages, exudates with or without papilloedema. We
      hypothesised that patients with "lone" papilloedema and severe hypertension were
      suffering from a disease which was identical in aetiology and outcome to
      conventional MHT. There were no significant differences in age, mean blood
      pressure, proteinuria or renal function at presentation, ethnic composition,
      smoking status and followup blood pressure control between the papilloedema group
      and those presenting with conventional MHT. Clinical features at presentation in
      the papilloedema only group included strokes in 4, visual disturbance in 2,
      headaches in 3 and heart failure in 1 patient. Many patients however had no
      complications at presentation. After a mean followup of 59.8 months, of the
      "lone" papilloedema group, 7 patients (30.4%) were still alive, 1 patient was on
      renal dialysis therapy, 13 were dead (56.5%) and 2 (8.7%) were lost to followup.
      The commonest causes of death were stroke in 4 patients, renal failure in 4 and
      heart disease in 2. This was a similar pattern of mortality to those patients
      with "conventional" MHT. Lifetable analyses showed a median survival of 35.9
      months for the papilloedema group which was significantly worse than the 108.7
      months for the conventional MHT group (Lee-Desu statistic 4.04, p = 0.045). We
      suggest that patients with high blood pressure and lone bilateral papilloedema
      may comprise a hitherto unrecognised subgroup of patients with MHT. Once
      intracerebral pathology has been excluded, these patients need to be treated as
      aggressively as those with MHT.

PMID- 8746601
TI  - Diet and exercise intervention have favourable effects on blood pressure in mild
      hypertensives: the Oslo Diet and Exercise Study (ODES).
AB  - The purpose of this study was to investigate the effect of 1-year diet
      intervention, exercise intervention and both combined on blood pressure (BP) in
      normotensives and mild hypertensives. Two hundred and nineteen sedentary middle
      aged men and women with slightly deranged coronary heart disease (CHD) risk
      factors were randomised to a control, a diet, an exercise and a diet + exercise
      group. Based on baseline diastolic BP, participants were divided into tertiles,
      giving baseline average BP of 141.4/96.7 in tertile 1, 130.7/87.6 in tertile 2
      and 121.9/79.0 in tertile 3. The 1-year net-difference in BP between the
      intervention groups and the control group decreased across the tertiles; in
      tertile 1 being -11.2/-6.7 (p < 0.05), -11.3/-6.7 (p < 0.05 for systolic BP only)
      and -7.0/-5.1 (NS) in the combined, diet and exercise group respectively.
      Triglycerides, HDL cholesterol, and insulin variables were significantly and
      favourably changed, the changes being most marked in the combined group. The
      results show that diet and diet + exercise are about equally effective in
      reducing BP, and the effects may be dependent on the baseline level. Within the
      upper tertile of baseline BP, the decline in BP in the combined intervention and
      the diet group are almost comparable to those obtained with drug treatment. In
      addition, other important CHD risk factors were all changed in a beneficial
      direction.

PMID- 8746602
TI  - Trough-to-peak versus surface ratio in the assessment of antihypertensive agents.
      APTH Investigators. Ambulatory Blood Pressure and Treatment of Hypertension.
AB  - This study investigated whether the 'surface ratio', a novel index to
      characterize long-acting antihypertensive agents, would provide a more
      reproducible estimate of the duration of the antihypertensive effect than the
      more commonly used trough-to-peak ratio. In 66 hypertensive patients (diastolic
      pressure on conventional measurement > 95 mmHg), the ambulatory blood pressure
      was measured on a placebo at baseline and 2 months later, while the patients took
      10 mg lisinopril once a day between 7 p.m. and 11 p.m. Diurnal treatment effect
      curves were obtained by subtracting the blood pressure at baseline from the
      corresponding value at 2 months for all time intervals considered in the
      analysis. In order to calculate the surface ratio, the area under the treatment
      effect curve was divided by the product of the maximal blood pressure lowering
      effect and the dosing interval (24 h). Reproducibility of the trough-to-peak and
      surface ratios was investigated by the Bland and Altman techniques. At 2 months,
      lisinopril reduced (+/- standard deviation) the 24 h pressure by 13 +/- 16 mmHg
      systolic and by 8 +/- 8 mmHg diastolic (p < 0.001). According to the usual
      approach, disregarding inter-individual variability, the trough-to-peak ratio was
      0.7 for systolic and diastolic pressure. When in individual patients diurnal
      treatment effects curves with a 1 h resolution were investigated, the median
      trough-to-peak ratio was 0.30 for systolic pressure (5th-95th percentile interval
      [PI]: -0.51, 0.82) and 0.28 for diastolic pressure (PI: -0.37, 0.78); the
      corresponding values for the surface ratio were 0.33 (PI: 0.03, 0.58) and 0.30
      (PI: -0.01, 0.55). In the same manner, the trough-to-peak ratios and surface
      ratios became larger when the individual blood pressure profiles were
      progressively smoothed by substituting 1 h averages by 2 h moving averages, 2 h
      averages, 3 h moving averages or by 3 h averages. The distributions of the trough
      to-peak ratios and surface ratios were non-normal in 37 of 40 instances (p <
      0.001, Shapiro-Wilk's test). Consistency was higher (p < 0.001) for the surface
      than for the trough-to-peak ratios. The within-subject reproducibility of the
      surface ratios tended to be superior to that of the corresponding trough-to-peak
      ratios. In conclusion, the surface ratio provides an index of the duration of
      action of antihypertensive agents. Moreover, in the present patients, the surface
      ratio tended to be characterized by a higher within-subject reproducibility than
      the trough-to-peak ratio.

PMID- 8746603
TI  - Combined treatment with captopril, hydrochlorothiazide and pravastatin in
      dyslipidemic hypertensive patients.
AB  - OBJECTIVES: Hypertension and hypercholesterolemia frequently coexist,
      necessitating concurrent treatments for both disorders. The present study aimed
      at evaluating the efficacy, the safety, and the toleration of captopril, an ACE
      inhibitor, hydrochlorothiazide, a diuretic, and pravastatin, a HMG-CoA reductase
      inhibitor co-administered in hypertensive patients in general practice. DESIGN:
      The patients were followed for 16 weeks and asked to comply with a lipid lowering
      diet for the whole period. Captopril, 50 mg/once daily, was administered alone
      for the first 4 weeks. Hydrochlorothiazide, 25 mg/day, was added after 4 weeks if
      required. Pravastatin treatment (20 mg/day) was started at the 8th week of the
      study and its dose was doubled 4 weeks later if needed. PATIENTS: A total of 603
      patients with hypertension (diastolic blood pressure > or = 95 mmHg) and
      dyslipidemia (total cholesterol > 6.5 mmol/l) were included. SETTING: The study
      was performed in general practice by 230 physicians. MAIN OUTCOME MEASURE:
      Determination of blood pressure, circulating levels of total cholesterol, HDL
      cholesterol and triglycerides, and blood chemistry for safety monitoring.
      RESULTS: At the end of the trial 75.1% of patients had their diastolic blood
      pressure < or = 90 mmHg and 43.5% a total cholesterol level < 6.5 mmol/l. The
      overall incidence of adverse events was 21.7%, leading to withdrawal in 10.9% of
      the total number of patients. The combined treatments had no deleterious effect
      on safety variables. CONCLUSIONS: Captopril, hydrochlorothiazide and pravastatin
      are effective and well tolerated medications to treat dyslipidemic hypertensive
      patients.

PMID- 8746604
TI  - Effects of cilazapril on renal haemodynamics and function in hypertensive
      patients: a randomised controlled study versus hydrochlorothiazide.
AB  - In this study the efficacy and safety of short-term cilazapril administration on
      renal haemodynamics were evaluated in mild to moderate hypertensive subjects. Our
      final goal was to evaluate whether the reduction in blood pressure achieved by
      treatment was associated with maintained renal function. After a run-in period
      with placebo, 40 hypertensive subjects without renal or cardiac diseases were
      randomly allocated to a double-blind 4 week controlled trial with cilazapril 5 mg
      once a day (20 patients) or hydrochlorothiazide 25 mg once a day (20 patients).
      Renal haemodynamics measurements included effective renal plasma flow (ERPF) and
      glomerular filtration rate (GFR) by radionuclide study using 131I-hippuran and
      99mTc, according to the methods described by Schlegel and Gates, respectively.
      Effective renal blood flow [ERBF = ERPF/(1-Ht)], filtration fraction (FF =
      GFR/ERPF) and renal vascular resistance (RVR = MBP x 80/ERBF) were calculated. At
      the end of cilazapril and hydrochlorothiazide administration significant
      decreases (p < 0.001) in SBP, DBP and MBP vs baseline values were observed. In
      the cilazapril group a significant decrease (p < 0.001) in RVR and FF and a
      significant increase (p < 0.001) in ERPF and ERBF were also found. In the
      hydrochlorothiazide group a significant decrease (p < 0.001) in RVR was found. No
      important side effects were observed with either treatment. In conclusion our
      data indicate that both cilazapril and hydrochlorothiazide reduced blood pressure
      equally well but only cilazapril improved renal blood flow and reduced filtration
      fraction.

PMID- 8746605
TI  - Angiotensin converting enzyme inhibitor therapy and acute pancreatitis.
AB  - Angiotensin converting enzyme (ACE) inhibitors are generally well tolerated.
      Worldwide, only few reports have been published associating pancreatitis with ACE
      inhibitor therapy. We report a case in whom there was no other likely explanation
      for the acute pancreatitis than enalapril therapy, which was temporally
      associated with the symptoms. Possible mechanisms underlying the induction of
      pancreatitis by ACE inhibitors are discussed. With the increasing use of ACE
      inhibitors, the incidence of rare adverse effects such as potentially lethal
      pancreatitis is likely to increase. Clinicians need to be aware of this
      association.

PMID- 8746606
TI  - Contractile responses to various inotropic agents in isolated hearts obtained
      from hypertensive diabetic rats.
AB  - The profile of the contractile effects of calcium ions, the Ca(2+)-entry promoter
      Bay K 8644 and two alpha 1-adrenoceptor agonists (cirazoline and ST587) was
      studied in isolated perfused Langendorff hearts taken from spontaneously
      hypertensive rats (SHR) and Wistar Kyoto rats (WKY) with simultaneous diabetes.
      In both the hypertensive and the diabetic state the isolated hearts showed a
      tendency to an impaired inotropic response (increase in left ventricular pressure
      (LVP)) towards an increase of extracellular calcium ions. The impaired inotropic
      response was most pronounced in hearts of rats with simultaneous diabetes and
      hypertension. The Ca(2+)-influx promoter Bay K 8644 did not influence the
      maximally developed LVP in (diabetic) SHR and WKY preparations. The inotropic
      responses to both cirazoline and ST587 were increased in hearts from diabetic WKY
      and diabetic SHR, when compared with those from control WKY and SHR.
      Hypertension, however, blunted the inotropic response to ST587 but not that to
      cirazoline when compared to hearts from control WKY or diabetic WKY. The present
      study indicates that the combination of hypertension and diabetes leads to
      progressive cardiac deterioration, likely to be the result of important changes
      in calcium homeostasis.

PMID- 8746607
TI  - Antidepressant pharmacotherapy: economic evaluation of fluoxetine, paroxetine and
      sertraline in a health maintenance organization.
AB  - The present study was designed to compare direct health service expenditures, for
      the treatment of depression, among patients enrolled in a health maintenance
      organization, and prescribed one of three selective serotonin reuptake
      inhibitors, fluoxetine, paroxetine or sertraline. Information regarding
      depression-related health service use was derived from the computer archive of a
      network-model health maintenance organization system serving 700,000
      beneficiaries. A total of 744 health maintenance organization beneficiaries were
      found to satisfy the study selection criteria. Multivariate regression analysis
      was used to determine the incremental influence of selected demographic,
      clinical, financial and provider characteristics on health service expenditures
      related to the treatment of depression (ICD-9-CM, or DSM-IV code 296.2) 1 year
      after the start of antidepressant pharmacotherapy. Multivariate findings indicate
      that treatment with paroxetine increases average expenditures for physician
      visits ($31.93; P < or = 0.05), psychiatric visits ($19.33; NS), laboratory tests
      ($2.35; P < or = 0.05), hospitalizations ($85.33; P < or = 0.05), psychiatric
      hospitalizations ($82.01; P < or = 0.05), and antidepressant pharmacotherapy
      ($63.72; P < or = 0.05), for a total per capita increase in health service use of
      $284.68 (P < or = 0.05), compared with treatment with fluoxetine. Sertraline
      treatment increases average expenditures for physician visits ($21.74; P < or =
      0.05), psychiatric visits ($56.79; P < or = 0.05), laboratory tests ($1.21; P <
      or = 0.05), hospitalizations ($70.59; P < or = 0.05), psychiatric
      hospitalizations ($95.75; P < or = 0.05), and antidepressant pharmacotherapy
      ($69.85; P < or = 0.05), for a total per capita increase in health service use of
      $315.96 (P < or = 0.05), compared with treatment with fluoxetine. Economic
      comparisons between paroxetine and sertraline did not demonstrate any significant
      differences in expenditures for the health services examined.

PMID- 8746608
TI  - Azithromycin compared with clarithromycin in the treatment of adult patients with
      acute purulent tracheobronchitis: a cost of illness study.
AB  - Adult, professionally active patients with acute purulent tracheobronchitis were
      treated with azithromycin (3 or 5 days; n = 62) or clarithromycin (7 to 10 days;
      n = 69) in an open, randomized study. Bronchitis-related costs and treatment
      efficacy were assessed at day 5-6 and day 14-21. Both antibiotics were of equal
      clinical efficacy, although the median time to improvement of symptoms was
      significantly shorter for azithromycin patients than for clarithromycin patients.
      Some 77% of azithromycin patients and 78% of clarithromycin patients were unable
      to work for at least 1 day. The total time when patients were unable to work was
      shorter for azithromycin patients than for clarithromycin patients, but this
      difference did not remain significant when weekends and holidays were taken into
      account. Further studies are needed to assess the impact of azithromycin on time
      to clinical improvement, on lost working days, and on the associated costs.

PMID- 8746609
TI  - Factors related to aortic pulse-wave velocity in patients with non-insulin
      dependent diabetes mellitus.
AB  - The factors that influence the severity of large vessel pathology in patients
      with non-insulin-dependent diabetes mellitus (NIDDM) were investigated in 154
      randomly selected patients. Measurements of aortic pulse-wave velocity were used
      to quantify the severity of large vessel pathology. The results showed that of
      the 20 variables considered, age, systolic blood pressure, duration of disease
      and serum creatinine were all significantly correlated with pulse-wave velocity.
      Multiple regression analysis with pulse-wave velocity as the criterion variable
      showed that age, systolic and diastolic blood pressures were all significant
      explanatory variables, with age carrying the greatest weight. The findings
      suggest that controlling blood pressure is most important as a means of
      containing large vessel pathology in patients with NIDDM.

PMID- 8746610
TI  - Effects of the neuropeptide, substance P, on lymphocyte proliferation in
      rheumatoid arthritis.
AB  - There is evidence supporting the involvement of the neuropeptide, substance P, in
      the pathogenesis of rheumatoid arthritis. In view of the suggested role of T
      cells in this disease, we have investigated the effects of substance P on mitogen
      induced lymphocyte proliferation in rheumatoid arthritis patients. The peripheral
      blood mononuclear cells from 20 patients with rheumatoid arthritis and 25
      controls were cultured in the presence or absence of substance P (10(-10) M to
      10(-6) M) and stimulated with phytohaemagglutinin or concanavalin A. After 3 days
      of culture the proliferative responses were determined by measuring [3H]thymidine
      incorporation into the cells. Substance P enhanced, in a dose-dependent manner,
      the lymphocyte proliferative responses both in rheumatoid arthritis patients and
      in controls. Although there was a trend towards a greater enhancing effect in the
      rheumatoid arthritis patients, this was not statistically significant. Some
      individual patients with rheumatoid arthritis showed enhancements of lymphocyte
      proliferation with substance P that were clearly outside the range seen in
      healthy controls. The possibility that substance P has a role in the pathogenesis
      of rheumatoid arthritis through the up-regulation of lymphocyte activation should
      be considered in further studies of the immunomodulatory properties of substance
      P in arthritis.

PMID- 8746611
TI  - Prescribing rationale and budgetary outcomes associated with the introduction of
      a combined formulation of diclofenac sodium and misoprostol in Canada.
AB  - The budgetary impact of prescribing a combined formulation of diclofenac sodium
      and misoprostol to patients previously using nonsteroidal anti-inflammatory
      agents (NSAIDs), cytoprotective agents, or a combination of agents from both
      therapeutic categories is assessed, as is the clinical rationale for prescribing
      the combined formulation. Analysis of data for Canada on claims paid by third
      parties showed that the use of the combined formulation in Canada had resulted in
      significant initial overall savings and that the greatest cost savings were made
      for those who had previously used both an NSAID and a cytoprotective
      concomitantly. The inclusion of shadow costs (secondary costs) indicates that the
      use of the combined formulation over a 6-month period involves very low shadow
      costs (medical expenses related to ulcer treatment) compared with other NSAIDs:
      the shadow cost multiplication factor was 1.03 for the combined formulation
      compared with 1.22 to 3.47 for other NSAIDs. Pharmaceutical costs alone are
      insufficient for evaluating total budgetary impacts.

PMID- 8746612
TI  - Factors related to stress in patients with non-insulin-dependent diabetes
      mellitus.
AB  - Stress was assessed using State-Trait Anxiety Inventory scores in 40 non-insulin
      dependent diabetes mellitus (NIDDM) patients, and the results were compared with
      those for 40 sex- and age-matched healthy controls. Fludiazepam was administered
      to the patients for 12 weeks and stress was reassessed. The Manifest Anxiety
      Scale score correlated with Trait (r = 0.548, P < 0.0001) and State (r = 0.474, P
      = 0.0001) scores, validating the latter as measurements of stress. Both Trait
      (43.4 vs 35.8, P < 0.001) and State (41.6 vs 33.8, P < 0.001) scores were
      significantly higher in NIDDM patients than in healthy controls. Administration
      of an anxiolytic, fludiazepam (0.25 mg, three times daily, orally) for 12 weeks
      lowered Trait score (43.5 to 36.9, P < 0.0001), State score (41.6 to 35.8, P <
      0.0002), glycosylated haemoglobin (8.4 to 7.3%, P < 0.0001), systolic blood
      pressure (151.2 to 143.4 mmHg, P < 0.0017) and diastolic blood pressure (84.2 to
      77.7 mmHg, P < 0.0018). Multiple regression analysis revealed that the
      significant explanatory variables for the change in State score during anxiolytic
      administration were the changes in total cholesterol, high-density lipoprotein
      cholesterol, triglycerides, apolipoprotein B:A1 and glycosylated haemoglobin (R2
      = 0.3224, P < 0.0022). The results indicate that stress is detected at a higher
      frequency in patients with NIDDM than in healthy controls, and that blood glucose
      and lipid metabolic factors are significant explanatory variables for this
      stress. This stress is correlated with glucose metabolism and blood pressure and,
      moreover, these factors could all be proved concomitantly by the administration
      of an anxiolytic.

PMID- 8746613
TI  - Suppression of mesangial-cell proliferation by trapidil in glomerulonephritis
      induced by anti-thymocyte serum in rats.
AB  - Trapadil (Mochida Pharmaceuticals, Japan), an antiplatelet drug, suppresses the
      growth of several cell types and is thought to antagonize platelet-derived growth
      factor. The effects of trapidil on mesangial-cell proliferation in
      glomerulonephritis induced by anti-thymocyte serum in Wistar rats were
      investigated. Control rats were treated with phosphate-buffered saline (group I);
      group II rats were injected with a single dose of anti-thymocyte serum (8 ml/kg
      body weight), and group III rats were treated with both a single dose of anti
      thymocyte serum (8 ml/kg body weight) and with trapidil (5 mg/kg body
      weight/day). Three rats in each group were killed on day 3, and the other three
      on day 10. Control rats showed no significant histological changes on day 3 or
      day 10. In group II, on day 3, there was a marked decrease in glomerular cell
      numbers, with mesangiolysis. Histologically severe mesangial-cell proliferation
      with expansion of mesangial areas was noted on day 10. None of the rats in group
      III showed mesangial alterations, histologically, indicating that mesangial-cell
      proliferation was suppressed by trapidil. This suppression may result from
      antagonism of the binding of platelet-derived growth factor to the specific
      surface receptors in the mesangial cells. Trapidil may have clinical value in the
      treatment of mesangial-cell proliferative glomerular diseases.

PMID- 8746614
TI  - Is there a correlation between cardiac sympathetic neuropathy or diabetic somatic
      neuropathy and glycosylated haemoglobin or blood pressure in patients with non
      insulin-dependent diabetes mellitus?
AB  - The possibility that glycosylated haemoglobin levels and/or blood pressure might
      correlate with cardiac sympathetic neuropathy and/or diabetic somatic neuropathy
      was investigated in patients with non-insulin-dependent diabetes mellitus.
      Sympathetic nerve function was quantified by analysis of
      [123I]metaiodobenzylguanidine accumulation in the cardiac muscle. Somatic nerve
      function was assessed by measuring the motor nerve conduction velocities of the
      peroneal and tibial nerves, and the sensory nerve conduction velocity of the
      sural nerve. None of the parameters of cardiac sympathetic neuropathy or diabetic
      somatic neuropathy showed any correlation with blood pressure, nor was there any
      evidence of a correlation between cardiac sympathetic neuropathy and glycosylated
      haemoglobin levels; there was, however, a significant correlation between
      diabetic somatic neuropathy (as indicated by tibial nerve conduction velocity)
      and glycosylated haemoglobin levels. The results are consistent with the view
      that different mechanisms are involved in the two types of neuropathies.

PMID- 8746615
TI  - Helicobacter felis as a cofactor alone or together with stress in cryptosporidial
      activation in mice.
AB  - Cryptosporidiosis is caused by a protozoan parasite, mainly found in animals,
      which usually results in transient, mild gastroenteritis in humans but can cause
      severe and prolonged disease in immunocompromised individuals. Immunocompetent
      mice, naturally infected with Cryptosporidium muris, were used to investigate the
      effects of inoculation with Helicobacter felis and of stress on the activity of
      the C. muris infection, as indicated by histopathological examination of their
      stomachs. The results indicate that both H. felis inoculation and/or stress
      activate C. muris and cause gastric inflammation. The extent of the activation of
      C. muris depends on the duration of the stress.

PMID- 8746616
TI  - Immunohistochemical analysis of type III and IV collagens in tubulointerstitial
      damage in human benign nephrosclerosis.
AB  - Prolonged hypertension causes structural changes including glomerulosclerosis and
      tubulointerstitial damage of the kidney, termed benign nephrosclerosis. It is
      generally accepted that, in benign nephrosclerosis, increased accumulation of
      extracellular matrix in the glomeruli results in glomerulosclerosis. Little is
      known, however, about the possible role of the extracellular matrix in the
      tubulointerstitial damage in benign nephrosclerosis. In this study, the possible
      roles of type IV basement-membrane collagen and type III interstitial collagen in
      tubulointerstitial damage caused by hypertension were explored.
      Immunohistochemical techniques were used to investigate the distribution of type
      III and type IV collagens in the kidney sections of 15 patients with benign
      nephrosclerosis with tubulointerstitial damage and in 10 controls. In the control
      renal sections strong immunostaining for type III collagen was found in the
      interstitium and immunostaining for type IV collagen was present in the tubular
      basement membrane and weakly in the interstitium. In the patients with
      tubulointerstitial damage there was increased immunostaining for both type III
      and type IV collagens in the expanded interstitium and damaged tubules than was
      found in the control kidney sections. These findings indicate that increased
      accumulation of both type III and type IV collagens might play a significant role
      in the tubulointerstitial damage in benign nephrosclerosis.

PMID- 8746617
TI  - Can alpha-glucosidase inhibitors reduce the insulin dosage administered to
      patients with non-insulin-dependent diabetes mellitus?
AB  - For 10 patients (three women and seven men) with noninsulin-dependent diabetes
      mellitus, who had been given insulin (22.6 +/- 19.6 U/day) and had frequently
      shown hypoglycaemia, the insulin dose was slightly reduced and the administration
      of an alpha-glucosidase inhibitor was simultaneously started. Hypoglycaemic
      symptoms disappeared immediately and completely, and sugar metabolism immediately
      before the withdrawal of treatment was not aggravated: the glycosylated
      haemoglobin level was unchanged and the post-prandial blood glucose level was
      increased though not significantly. The results of the present study indicate
      that the combined used of an alpha-glucosidase inhibitor with a reduced insulin
      dose improves the quality of life of patients and may improve hyperinsulinaemia.

PMID- 8746618
TI  - Effect of alpha-glucosidase inhibitor in combination with sulphonylurea compounds
      on lipid profile in patients with non-insulin-dependent diabetes mellitus.
AB  - The effects of administration of an alpha-glucosidase inhibitor and a
      sulphonylurea compound on lipid profile were investigated in patients with non
      insulin-dependent diabetes mellitus, (NIDDM) previously treated with
      sulphonylurea compounds alone, but in whom metabolic control was inadequate. A
      group of patients (n = 10) were treated with the alpha-glucosidase inhibitor at a
      dose of 0.2 mg, three times daily, for 4 weeks. Treatment significantly reduced
      the post-prandial glucose level and the serum total cholesterol level. In
      addition, there were non-significant reductions in the triglyceride and very low
      density lipoprotein levels. These preliminary results suggest that administration
      of alpha-glucosidase inhibitors might improve the lipid profile of patients with
      NIDDM.

PMID- 8746619
TI  - Insulin secretion levels necessary for efficacy of an alpha-glucosidase inhibitor
      on glucose metabolism in patients with non-insulin-dependent diabetes mellitus.
AB  - Twenty patients with non-insulin-dependent diabetes mellitus whose glucose
      metabolism was unsatisfactory, even though they were receiving appropriate
      dietary therapy, were treated with an alpha-glucosidase inhibitor (0.6 mg/day)
      for 12 weeks. The connecting peptide immunoreactivity value (selected as the
      evaluation criterion of post-prandial endogenous insulin secretion) was compared
      in patients with and without improved glycosylated haemoglobin levels. A
      significant difference was found between the connecting peptide immunoreactivity
      value of the group with improved glycosylated haemoglobin levels (5.0 +/- 1.0
      ng/ml) and that in the group without the improvement (2.7 +/- 0.9 ng/ml).

PMID- 8746620
TI  - Can alpha-glucosidase inhibitors reduce the dosage of sulphonylurea compounds
      needed by patients with non-insulin-dependent diabetes mellitus?
AB  - The effects of treatment with an alpha-glucosidase inhibitor and a reduced dose
      of sulphonylurea were investigated in patients with non-insulin-dependent
      diabetes mellitus who had previously been treated with sulphonylurea compounds
      but who were hypoglycaemic at times. Treatment with a daily dose of 0.6 mg alpha
      glucosidase inhibitor and a reduced dose of the previously used sulphonylurea
      compound for 4 weeks did not significantly affect the glycosylated haemoglobin
      level. The post-prandial blood-glucose concentration of the patients was
      unchanged after treatment compared with its value immediately before treatment
      but differed significantly compared with the value 4 weeks before treatment (P <
      0.03); it was considered likely that this change was due to a seasonal increase
      in calorie intake at the end of the treatment period. Symptoms related to
      hypoglycaemia disappeared in all of the treated patients.

PMID- 8746621
TI  - An open study of mupirocin in Libyan patients with skin infections.
AB  - In an open study in Libya 48 patients suffering from skin infections, usually
      caused by staphylococci and streptococci, were treated with a new topical
      antibiotic, mupirocin, applied three times daily for 7 days. By day 7 of
      treatment 93.5% of patients were asymptomatic and were considered cured, and 100%
      were considered cured 1 week later. In total, 50 bacterial strains were isolated,
      of which, 86% were staphylococci and 14% were streptococci. Neither adverse
      events nor cutaneous reactions were reported. Mupirocin 2% ointment proved to be
      effective and safe in the treatment of primary and secondary skin infections.

PMID- 8746622
TI  - Immunoaffinity purification of epitope-tagged human beta 2-adrenergic receptor to
      homogeneity.
AB  - To obtain large quantities of pure human beta 2-adrenergic receptor (beta 2-AR)
      needed for structural studies, an efficient method for beta 2-AR purification was
      developed using a recombinant receptor with an eight amino acid epitope at its C
      terminus. This epitope is recognized by KT3-monoclonal antibody. The epitope
      tagged beta 2-AR was expressed in Sf9 cells with a specific activity of 5-20
      pmol/mg of membrane protein. The epitope-tagged and wild-type receptors had
      identical ligand binding properties. The tagged receptor was solubilized using
      dodecyl-beta-maltoside with a quantitative yield. Solubilized epitope-tagged
      receptors were partially purified by KT3-mAb immunoaffinity in 60-70% yield.
      Further purification of the receptors on an alprenolol-affinity column resulted
      in a homogenous preparation with an overall yield of > 30%. The purified receptor
      was concentrated to > 1 mg/ml without loss of ligand binding activity.

PMID- 8746623
TI  - Expression and purification of a synthetic human obese gene product.
AB  - Human obese (hOB) protein was recently identified as a secreted hormone-like
      factor that is exclusively produced by adipose tissue and appears to regulate the
      size of the body's fat stores. We describe a rapid and efficient repetitive
      extension PCR method for the construction of a 453-bp synthetic hOB gene with
      high-frequency codons to optimize expression in Escherichia coli. The use of a
      bacterial signal sequence fused to hOB together with expression of bacteriocin
      release protein resulted in efficient release of hOB into the culture medium. The
      protein was readily purified to homogeneity from the culture medium using a two
      step procedure.

PMID- 8746624
TI  - Overexpression in Escherichia coli, folding, purification, and characterization
      of the first three short consensus repeat modules of human complement receptor
      type 1.
AB  - We have developed a simple expression, isolation, and folding protocol for an SCR
      oligomer comprising the first three SCRs of complement receptor Type 1 (C3b/C4b
      receptor, CD35). A T7 RNA polymerase expression system in Escherichia coli was
      used to express the oligomer as inclusion bodies. The oligomer was recovered from
      solubilized inclusion bodies using batch adsorption on SP-Sepharose. The oligomer
      was folded by one-step dilution in 20 mM ethanolamine/1 mM EDTA supplemented with
      1 mM GSH/0.5 mM GSSG. The folded material was processed to a concentrated (> 20
      mg/ml), usable product of greater than 98% purity using a combination of
      ultrafiltration, ammonium sulfate treatment, hydrophobic interaction, and size
      exclusion chromatography. The yield of folded material varied between 6 and 15
      mg/liter culture. The oxidation states of the 12 cysteine residues in SCR(1-3)
      were identified by HPLC of peptide fragments from a tryptic digest using dual
      UV/fluorescence detection, collection of selected peaks, and N-terminal
      sequencing. This methodology confirmed the expected location of disulfide
      bridges. Equilibrium and velocity sedimentation studies are interpreted in terms
      of a single sedimenting species with molecular weights of 21,629 and 21,063 by
      these respective techniques. These values compare to the predicted molecular
      weight, from amino acid composition, of 21,817. The hydrodynamic properties of
      the molecule indicate that it is asymmetric with an axial ratio of 1:5.2 or
      equivalent dimensions of 21 x 110 A. SCR(1-3) has an unusual CD spectrum
      exhibiting a broad maximum at 220-230 nm and a minimum at 190 nm. There was
      little evidence of classical secondary structure. The product exhibited
      concentration-dependent inhibition of complement-mediated lysis of sensitized
      sheep red blood cells.

PMID- 8746625
TI  - Expression of soluble human interleukin-2 receptor alpha-chain in Escherichia
      coli.
AB  - A soluble, biologically active form of IL-2R alpha known as delta MST and
      consisting of the 178 N-terminal amino acid residues of the mature protein was
      directly expressed in the cytoplasm and the periplasm of Escherichia coli.
      Because it was not glycosylated, the E. coli protein was substantially less
      heterogeneous than delta MST expressed in insect cells. Nevertheless, it
      manifested equivalent biological activity in an IL-2 binding assay. The level of
      active delta MST production was higher when the protein was expressed in
      secretable form with a bacterial signal peptide than when it was produced in the
      cytoplasm, probably because the oxidizing environment and the presence of
      disulfide isomerases in the periplasm facilitated the correct folding of delta
      MST.

PMID- 8746626
TI  - Identification of an inhibitory element within the human 68-kDa (U1)
      ribonucleoprotein antigen.
AB  - Various nuclear proteins are the major targets of autoimmune responses in various
      rheumatic disorders. In particular, autoantibodies directed against a 68-kDa
      protein associated with the (U1) RNA-containing small nuclear ribonucleoprotein
      complexes typically occur in sera of patients with mixed connective tissue
      disease and related rheumatic disorders, such as systemic lupus erythematosus,
      and therefore are very useful as a serological marker. For establishing powerful
      immunoassays, it was necessary to generate recombinant human P68 antigen as the
      antigenic target. In this study we demonstrated that the cDNA coding for the full
      length human P68 antigen could not be expressed by a traditional bacterial vector
      system due to a putative inhibitory sequence designated as inhibitory sequence X
      which is located between the autoreactive domains C' and D' of the human P68
      antigen. The construction of corresponding hybrid plasmids carrying two
      functional and independent gene blocks indicated the trans-active function of the
      inhibitory sequence X, which could be localized by expression studies of various
      deletion constructs. Comparable Northern blot analysis clearly demonstrated that
      the inhibitory sequence X could act on the translation of the P68 mRNA. After
      excision of the inhibitory sequence X a dramatic increase in the production of
      recombinant human P68 antigen was observed.

PMID- 8746627
TI  - Overproduction and one-step purification of Escherichia coli UDP-N
      acetylglucosamine enolpyruvyl reductase.
AB  - The Escherichia coli gene murB, encoding the enzyme uridine-5'-diphospho-N-acetyl
      2-amino-2-deoxy-3-O-lactylglucosenicoti namide adenine dinucleotide phosphate
      oxidoreductase (EC 1.1.1.158) (EP-reductase), the second enzyme in the
      peptidoglycan biosynthetic pathway, has been amplified using PCR technology with
      the Kohara recombinant lambda phage E11C11 (534) as template. The synthetic gene
      was subcloned into the NdeI and BamHI restriction sites of the expression vector
      pT7-7, designed to utilize T7 RNA polymerase to direct transcription of the
      target gene, in a two-step procedure. The first step involved the directional
      insertion of the 590-bp NdeI to BamHI restriction fragment of murB into the pT7-7
      vector to give the plasmid pT7-7-murB-590. The construction of the desired
      overproducing plasmid was completed by the bidirectional insertion of the 442-bp
      BamHI to BamHI restriction fragment of murB into a similarly restricted pT7-7
      murB-590 plasmid followed by restriction digestion to select the properly
      oriented insert, pT7-7-murB. Overexpression of EP-reductase from the E. coli
      strain BL 21 (DE 3) containing the pT7-7-murB gene, after induction, allowed the
      production of 36 mg of target protein per 3 wet grams of E. coli cells. The EP
      reductase was purified in a single step utilizing dye-ligand chromatography to
      yield 30 mg of pure protein. The availability of these levels of reductase will
      allow the mechanism of this pivotal enzyme to be thoroughly studied as a
      potential target for the design of a new generation of antibiotics. In addition,
      the EP-reductase generated in this study has been utilized as a coupling enzyme
      to assay the first enzyme in the peptidoglycan biosynthetic pathway, UDP-N
      acetylglucosamine enolpyruvyl transferase, and these results are also presented.

PMID- 8746628
TI  - Overexpression and rapid purification of biologically active yeast proliferating
      cell nuclear antigen.
AB  - Yeast proliferating cell nuclear antigen (yPCNA) is a cell-cycle-regulated
      protein that has been shown to be required for the efficient elongation of primed
      DNA templates by DNA polymerase delta in vitro. We have expressed yPCNA to a high
      level (> or = 30% of the total cellular protein) with and without a six-residue
      histidine tag at its amino-terminus. Both forms of the recombinant protein were
      found to be biologically active and no significant differences were observed
      between the two forms. In this report we describe an efficient method of
      extraction of DNA binding proteins, such as yPCNA, overexpressed in Escherichia
      coli. The presence of a (His) delta tag on the polypeptide permitted rapid and
      high-yield single-step purification of the protein (approximately 60 mg of
      purified yPCNA per liter of induced cell culture) by immobilized metal affinity
      chromatography using an imidazole gradient elution procedure. The purified yPCNA
      was used to characterize the biological activity and tertiary structure of the
      protein. Chemical crosslinking and size-exclusion FPLC studies indicated that
      both forms of the protein have a trimeric-oligomeric structure in solution. Taken
      together these results indicate that both forms of the recombinant yPCNA were
      similar to the endogenous protein in their biochemical properties. The strategies
      presented here are designed to maximize the yield of recombinant protein and
      should prove useful to the purification of other recombinant DNA binding
      proteins.

PMID- 8746629
TI  - Purification of recombinant shiga-like toxin type I B subunit.
AB  - Shiga-like toxin type I (SLT-I) is a cytotoxin produced by certain strains of
      Escherichia coli. SLT-I is a bipartite molecule comprised of A (SLT-IA) and B
      (SLT-IB) subunits. In holotoxin, five B subunits are arranged in a pentameric
      ring and bind to globotriaosylceramide receptors on the surface of susceptible
      eukaryotic cells. The SLT-IB pentamer is noncovalently associated with one A
      subunit that has N-glycosidase activity and ultimately causes the death of
      targeted cells. Using a previously described overexpression vector, plasmid
      SBC32, we developed a two-step procedure for the purification of biologically
      active recombinant SLT-IB. Periplasmic proteins were extracted from E. coli
      JM105(pSBC32), fractionated by ammonium sulfate precipitation, and separated by
      isoelectric focusing in a pH 3-10 gradient. SLT-IB was present in fractions with
      pH values between 5.0 and 6.0, consistent with its reported pI of 5.8. SLT-IB was
      purified to homogeneity in a second step by native polyacrylamide gel
      electrophoresis. Purified SLT-IB was characterized for biological and biochemical
      activity. When analyzed by native polyacrylamide gel electrophoresis, the
      majority of SLT-IB had an apparent molecular weight of 38,900, consistent with a
      pentameric subunit association. Chemical cross-linking of SLT-IB with
      disuccinimidyl suberate resulted in species with molecular weights corresponding
      to dimeric, trimeric, tetrameric, and pentameric forms of B subunit. SLT-IB was
      not cytotoxic to Vero cells at concentrations as high as 10 micrograms/ml and
      protected Vero cells from native SLT-I. Purified SLT-IB maintained its ability to
      associate with SLT-IA to form holotoxin that exhibited toxicity similar to native
      toxin.

PMID- 8746630
TI  - Rapid high-yield purification and liposome reconstitution of polyhistidine-tagged
      sensory rhodopsin I.
AB  - We have used Ni(2+)-affinity chromatography as a rapid and efficient method to
      purify a sensory rhodopsin I (SR-I) derivative containing six consecutive
      histidine residues at its C-terminus (His-tagged SR-I). The protein was expressed
      in Halobacterium salinarium by integrating the corresponding gene at the
      chromosomal bacterioopsin locus under the control of the bacterioopsin promoter.
      His-tagged SR-I retains native SR-I photochemical reactions in purified membranes
      and phototaxis signaling function in vivo. Immobilized Ni(2+)-affinity
      chromatography of membranes solubilized in 1% layryl maltoside provides a single
      step purification of the protein to electrophoretic homogeneity (> or = 90%
      pure). The procedure yields 1.7 mg pure photoactive protein/liter of culture (60%
      efficiency). This yield combined with engineered overproduction of the protein
      provides at least 120-fold greater amounts than that of a previously reported
      multistep purification procedure, permitting structural and biochemical analysis
      previously not feasible. The purified protein in lauryl maltoside at pH 5.3
      exhibits a visible absorption maximum at 587 nm characteristic of SR-I.
      Spectrometric titration reveals an alkaline-induced species at 550 nm previously
      observed with transducer-free SR-I in native membranes. A previously unreported
      structured absorption band at 400 nm, consistent with a deprotonated Schiff base,
      forms with the same pKa as the 550-nm species. His-tagged SR-I reconstituted into
      phosphatidylglycerol proteoliposomes retains properties of transducer-free SR-I
      in native membranes: its flash-induced absorption difference spectrum is
      identical, its photochemical reaction cycle kinetics show a similar pH
      dependence, and it forms a photoactive 550-nm species under alkaline conditions.
      These results indicate His-tagged SR-I reconstituted in proteoliposomes is
      suitable for analyzing SR-I interaction with its transducer protein in vitro.

PMID- 8746631
TI  - Purification and properties of insulin receptor ectodomain from large-scale
      mammalian cell culture.
AB  - Ectodomain of the exon 11+ form of the human insulin receptor (hIR) was expressed
      in the mammalian cell secretion vector pEE6.HCMV-GS, containing the glutamine
      synthetase gene. Following transfection of the hIR ectodomain gene into Chinese
      hamster ovary (CHO-K1) cells, clones were isolated by selecting for glutamine
      synthetase expression with methionine sulphoximine. The expression levels of
      ectodomain were subsequently increased by gene amplification. Production was
      scaled up using a 40-liter airlift fermenter in which the transfected CHO-K1
      cells were cultured on microcarrier beads, initially in medium containing 10%
      fetal calf serum (FCS). By continuous perfusion of serum-free medium into the
      bioreactor, cell viability was maintained during reduction of FCS, which enabled
      soluble hIR ectodomain to be harvested for at least 22 days. Harvests were
      concentrated 20-fold by anion-exchange chromatography. Optimal recovery of
      ectodomain from early harvests containing large quantities of serum proteins was
      achieved by insulin-affinity chromatography, whereas in later harvests
      purification was achieved by multistep chromatography. Analysis of the purified
      hIR ectodomain showed that it had a molecular weight by sedimentation equilibrium
      analysis of 269,500. Amino-terminal amino acid sequence analysis showed that the
      ectodomain was correctly processed to alpha and beta chains and that
      glycosylation characteristics were similar to those of native hIR. The integrity
      of the ectodomain was demonstrated by the recognition of conformation-dependent
      anti-hIR antibodies and by its binding of insulin (Kd approximately 2 x 10(-9)
      M). These results demonstrate the successful production and purification of hIR
      ectodomain by processes amenable to scale-up and in a form appropriate for
      structure/function studies of the ligand-binding domain of the receptor.

PMID- 8746632
TI  - Expression, purification, and characterization of acylphosphatase muscular
      isoenzyme as fusion protein with glutathione S-transferase.
AB  - A genetic construct consisting of the synthetic gene coding for human muscle
      acylphosphatase linked to the gene for glutathione S-transferase has been
      prepared. This gene was transformed into and expressed by the Escherichia coli
      strains DB1035 and TB1, respectively. The fusion protein was purified by affinity
      chromatography and subsequently cleaved to the fully active acylphosphatase,
      which was further purified by gel filtration chromatography. Such a purification
      procedure is very rapid and suitable for obtaining considerable amounts of enzyme
      at a very high yield. The purified human muscle acylphosphatase was fully active
      and showed structural features, as well as kinetic and stability parameters,
      identical to those of the native enzyme.

PMID- 8746633
TI  - Characterization of recombinant heparin cofactor II expressed in insect cells.
AB  - Recombinant human heparin cofactor II (rHCII) was expressed as a fully active
      protein in the High-Five insect cell line. A maximal protein concentration of 6
      micrograms/10(6) cells was achieved 2 days postinfection. Approximately 40
      micrograms of partially purified rHCII was routinely recovered from 50 ml of
      media after sequential heparin and Q-Sepharose affinity adsorption. rHCII had a
      slightly lower apparent molecular weight than blood plasma HCII (pHCII) due to
      differences in N-glycosylation. Like pHCII, rHCII formed a stable bimolecular
      complex with thrombin when assessed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The thrombin and chymotrypsin inhibitory properties of rHCII and
      pHCII were quite similar. In the absence of glycosaminoglycan, the thrombin
      inhibition rate (k2 x 10(-4) M-1 min-1) was 2.29 +/- 0.36 for rHCII and 3.38 +/-
      0.34 for pHCII. Chymotrypsin inhibition rates (k2 x 10(-5) M-1 min-1) were 6.2 +/
      2.0 for rHCII and 8.0 +/- 2.6 for pHCII. In the presence of glycosaminoglycans,
      the maximal thrombin inhibition rate (k2 x 10(-3) M-1 min-1) for rHCII was 10.4
      +/- 2.5 at 100 micrograms/ml heparin and 16.0 +/- 4.3 at 1000 micrograms/ml
      dermatan sulfate compared to 9.0 +/- 0.7 at 200 micrograms/ml heparin and 18.5 +/
      5.3 at 1000 micrograms/ml dermatan sulfate for pHCII. HCII inhibition of
      thrombin was blocked by a synthetic sulfated hirudin peptide in both the presence
      and the absence of glycosaminoglycan. The present report describes for the first
      time the expression and characterization of HCII in a baculovirus system and
      demonstrates the feasibility of using this system to obtain adequate amounts of
      biologically active rHCII for future structure-function studies.

PMID- 8746634
TI  - Expression of a synthetic gene encoding the anticoagulant-antimetastatic protein
      ghilanten by the methylotropic yeast Pichia pastoris.
AB  - Ghilantens are a family of cysteine-rich inhibitors of the clotting enzyme,
      factor Xa, that are produced in the salivary glands of the South American leech
      Haementeria ghilianii. In this study, a gene, designed from the amino acid
      sequence of a specific ghilanten isoform, was assembled from eight double
      stranded oligonucleotide fragments. A yeast expression plasmid, pPIC9HG-2, was
      constructed by making an inframe fusion of the ghilanten-coding sequences with
      the region encoding the pre-pro alpha-mating factor signal sequence for
      secretion. The expression of ghilanten in pPIC9HG-2 was under the control of the
      methanol-inducible, alcohol oxidase (AOX1) promoter. Pichia pastoris yeast
      strains KM 71 and SMD 1168 were transformed with linearized pPIC9HG-2 to target
      integration of the plasmid to the chromosomal 5'-AOX1 locus via homologous
      recombination. Both strains yielded His+ transformants that secreted a potent
      anticoagulant activity into the medium. Product yield was improved by using
      buffered media (pH 6.0) supplemented with either casamino acids or a mixture of
      yeast extract and peptone. The protease-deficient strain, SMD 1168, secreted
      about a twofold higher level of r-ghilanten than KM 71. Significant clonal
      variation in the expression of r-ghilanten was found among the His+
      transformants. A high producing clone was selected for production at the 2-liter
      shake flask and 10-liter bioreactor scales. r-Ghilanten was recovered from the
      fermentation broths in a single step by heparin Sepharose affinity
      chromatography. Protein sequence analysis of the amino terminus showed that the
      correct processing to yield mature ghilanten varied with the fermentation
      conditions.

PMID- 8746635
TI  - Expression of a highly unstable and insoluble transcription factor in Escherichia
      coli: purification and characterization of the fork head homolog HNF3 alpha.
AB  - The HNF3 alpha transcription factor is highly enriched in adult hepatocytes and
      activates many liver-specific genes; its expression in hepatic primordia and
      neurogenic tissue implies a developmental role. HNF3 alpha is a member of a
      family of proteins, including fork head in Drosophila, which bind DNA at specific
      sites using a newly defined "winged helix" structural motif. We describe here the
      expression and purification of full-length HNF3 alpha containing an amino
      terminal histidine tag and show that the protein binds DNA with dissociation
      constant in the sub-nanomolar range. The techniques used to isolate HNF3 alpha
      should be applicable to other members of the HNF3/fork head family which appear
      to be generally unstable and insoluble in Escherichia coli.

PMID- 8746636
TI  - Will mercury manometers soon be obsolete?
AB  - After a century of clinical use, the mercury sphygmomanometric technique of blood
      pressure (BP) measurement is under threat. There are three reasons for this:
      mercury is likely to be banned from hospital use because of the danger of
      toxicity, accurate automated devices are now available to replace the mercury
      sphygmomanometer and with the advent of 24 h ambulatory BP measurement into
      clinical practice, more reliance is being placed on BP behaviour rather than on
      casual measurements. The passing of the mercury sphygmomanometer from clinical
      practice raises two issues that merit deliberation. Without the mercury standard
      with which to compare measurements generated by algorithmic interpretation of BP,
      the clinician is dependent on the consistency and accuracy of such algorithms. If
      the millimetre of mercury is no longer the unit of measurement for BP, it will
      soon be replaced by the kilopascal thereby introducing, at least temporarily, the
      potential for uncertainty in clinical judgment.

PMID- 8746637
TI  - Assessment of blood pressure measurement quality in the baseline surveys of the
      WHO MONICA project.
AB  - Because of the general inavailability of reference standards, there exist no
      common procedures to assess the quality of blood pressure measurements in
      epidemiological population surveys. To approach this problem within the
      collaborative international WHO MONICA Project, a standardized assessment of BP
      measurement quality was developed and applied to the forty-seven baseline surveys
      of that project. The entire assessments were carried out in retrospect, that is,
      only after each population survey had been completed. The assessment was focused
      on the procedures of quality assurance and control as reportedly applied in each
      survey, and on quality indicators which were derived from the recorded blood
      pressure values of each survey. The definitions of specific quality assessment
      items were based on the MONICA project protocol and on sources in the pertinent
      literature. The available information on quality assurance and control procedures
      depended solely on self-reports by local survey organizers and on site visits,
      and was occasionally found to be at variance with the actual blood pressure
      recordings. Therefore, quality indicators derived from actual blood pressure
      recordings were far more informative and comparable between surveys. Each survey
      was rated as optimal, satisfactory, or unsatisfactory with regard to single
      quality items and these single scores were used jointly to compute a summary
      score of blood pressure measurement quality for each survey. This summary score
      indicated that 39 out of 47 MONICA baseline surveys showed optimal or
      satisfactory BP measurement quality. Limitations and potentials for improvement
      of quality assessments became apparent. We conclude that a standardized
      assessment of BP measurement quality in epidemiological population surveys seems
      feasible and propose that quality assessment methods similar to the ones
      suggested here become a routine part of future epidemiological analyses of blood
      pressure values and hypertension in populations. This should facilitate valid
      study comparisons.

PMID- 8746638
TI  - Cortisol excretion in essential hypertension.
AB  - A number of factors suggest that abnormalities of the adrenal cortex are present
      in essential hypertension. To determine whether altered cortisol excretion exists
      in essential hypertension, we have measured urinary free cortisol and cortisol to
      creatinine ratios in early morning urine specimens for 14 consecutive days. We
      have established a reference range for these parameters in 26 normotensive
      subjects. We have also compared these values in nine normotensive subjects and
      nine patients with essential hypertension closely matched for age, sex and body
      mass index. In the 26 normotensive subjects, urinary free cortisol was 240 +/- 13
      nmol/l (mean +/- s.e.m) and cortisol to creatinine ratio was 22 +/- l. In the
      nine hypertensive subjects, urinary free cortisol was 238 +/- 48 nmol/l and
      cortisol to creatinine ratio was 20 +/- 3. We have not demonstrated an
      abnormality of cortisol excretion in essential hypertension.

PMID- 8746639
TI  - Blood pressure response to exercise of obese and lean hypertensive and
      normotensive male adolescents.
AB  - Blood pressure response to exercise was studied in 100 male adolescents with
      essential hypertension, aged 13-18 years, during progressive maximal exercise
      test (Bruce Protocol). None received medication. Thirty of the subjects were
      obese hypertensive (OH), 30 were lean hypertensive (LH), 10 were obese
      normotensive (ON) and 30 were lean normotensive (LN). Quatelet index was used to
      measure obesity. Blood pressure was measured at rest and during treadmill test.
      Systolic blood pressure (SBP) values at rest showed a statistically significant
      difference between the hypertension and control groups (P < 0.0001), but not
      between the OH and the LH. During moderate exercise (stage II Bruce), however,
      this difference was significant (P < 0.0001). SBP > or = 160 mm Hg separated the
      hypertensives from the normotensives, with a sensitivity of 86.7%, specificity of
      85.0% and positive predictive value of 89.7%. During maximal exercise, the
      difference between values of OH and LH was also significant (P < 0.001).
      Approximately one third of the obese adolescents had SBP > 220 mm Hg, in maximal
      exercise. Heart rate response to exercise was greater in the ON group than in the
      LN. The findings suggest that: (1) obese hypertensive adolescents have higher
      blood pressures than lean hypertensives during exercise, indicating a more
      pathophysiological derangement in them; (2) the treadmill test discloses
      mechanisms, different than those at rest, which induce blood pressure elevation
      with exercise; and (3) moderate exercise identifies the hypertensive subjects.

PMID- 8746640
TI  - Changes in sodium intake and blood pressure in a community-based intervention
      project in China.
AB  - A sodium intervention project was carried out in Tianjin, China, as part of the
      Tianjin Project, which is a national pilot, community-based intervention
      programme to reduce non-communicable diseases. The aim of this 3 year sodium
      project was to evaluate the feasibility and effects of sodium reduction in the
      population. The evaluation of the programme was based on examinations of
      independent cross-sectional population samples in 1989 (1719 persons) and in 1992
      (2304 persons) in the intervention and matched reference areas. Food weighing and
      consecutive 3 day food records were used to measure dietary intake. The mean
      sodium intake fell 22 mmol/day in men and 11 mmol/day in women in the
      intervention area from 1989 to 1992. The reduction was significant in men (P =
      0.001) and near significance in women (P = 0.05). The sodium intake increased
      significantly in men in the reference area. There was a significant net reduction
      in sodium intake in men in the intervention area. This reduction was similar in
      different educational and occupational groups suggesting that the intervention
      had reached the whole community. The mean systolic blood pressure (SBP) decreased
      3 mm Hg for the total population and 2 mm Hg for normotensives in the
      intervention area. There was a significant net reduction in SBP both in all or in
      normotensive subjects. These results support the conclusion that community-based
      sodium intervention is feasible for hypertension prevention. However, the sodium
      intake is still very high in this population, which warrants further effective
      intervention.

PMID- 8746641
TI  - Blood pressure and myocardial perfusion in hypertensive patients with and without
      left ventricular hypertrophy.
AB  - To evaluate the effect of acute blood pressure (BP) changes on the myocardial
      perfusion in hypertensives, 10 patients with and 10 patients without left
      ventricular hypertrophy (LVH) were examined with 99TCm-Sestamibi scintigraphy at
      rest and after acute pharmacological BP reduction using nifedipine and captopril.
      Signs of LV ischaemia was quantified as the size of the hypoperfused area defined
      as isotope uptake below 70% of maximum LV uptake, and LVH was defined as
      ventricular mass (LVM) > 125 g/m2 BSA by use of echocardiography. Not significant
      relations between BP and size of the hypoperfused area was found at rest. During
      BP reduction patients with LVH had negative correlations (r = -0.58) between the
      size of the hypoperfused area and the systolic blood pressure (SBP) and the
      diastolic blood pressure (DBP) (r = -0.49) while patients without LVH showed
      positive correlations (SBP r = 0.60, DBP r = 0.48). The differences in
      correlation coefficients were significant (P < 0.01) for both. Thus, in
      hypertensives with LVH, ischaemia may develop at low BP providing a possible
      mechanism for the observed increased risk of cardiovascular events in some
      hypertensive patients with low achieved BP during follow-up. Until treatment
      goals are defined on scientific grounds, BP should not be decreased below 90 mm
      Hg in subjects with LVH.

PMID- 8746642
TI  - Long-term moderate sodium restriction does not adversely affect the serum
      HDL/total cholesterol ratio.
AB  - We examined the effect of long-term moderate sodium restriction on the HDL/total
      cholesterol ratio within a randomised trial of the effect of mineral salt on
      blood pressure (BP). Eighty nine untreated hypertensive men and women aged 55-75
      years were included in the analysis. During 24 weeks, 46 subjects used a low
      sodium, high potassium, high magnesium salt and 43 controls used common salt.
      Serum cholesterol levels were measured at baseline and at the end of the trial.
      After 24 weeks, 24 h urinary sodium was decreased by 41 mmol (95% Cl 23-60 mmol,
      P < 0.0001) in the mineral salt group compared with the controls. Serum total
      cholesterol was decreased in both groups, but 0.45 mmol/l (95% Cl 0.12-0.78, P =
      0.01) more in the controls than in the mineral salt group after adjustment for
      age, sex and changes in body weight, serum total protein and potassium excretion.
      Serum HDL-cholesterol was decreased by 0.07 mmol/l in the controls and increased
      by 0.06 mmol/l in the mineral salt group, yielding a difference of 0.14 mmol/l
      (95% Cl 0.05-0.22 mmol/l, P = 0.003). The change in HDL/total cholesterol ratio
      was more favourable in the mineral salt group than in the controls (0.014 and
      0.004 units, respectively, P = 0.014). We conclude that long-term moderate sodium
      restriction does not adversely affect the serum HDL/total cholesterol ratio and
      is a safe dietary measure for lowering BP.

PMID- 8746643
TI  - Quality of life in treated hypertension: a case-control community based study.
AB  - The aim of this case-control community study was to determine whether there was a
      difference in quality of life between hypertensive subjects and matched
      normotensive controls. Cases aged 40-79 years were randomly selected from a
      hypertensive register and matched with controls for age, sex, ethnicity and
      health centre. Cases had phase V diastolic blood pressure (DBP) > or = 100 mm Hg
      or systolic blood pressure (SBP) > or = 180 mm Hg, or were on anti-hypertensive
      medication. Controls had DBP < or = 90 mm Hg and no record of raised BP or anti
      hypertensive treatment within the past year. Quality of life was measured by self
      administered questionnaire. Data from 90 matched pairs, average age 62 years,
      with 47% men, were analysed; 80 hypertensive subjects were on anti-hypertensive
      medication. Hypertensive subjects showed an impairment in well-being compared
      with controls. They had a lower Health Status Index, had more sickness absence
      from work, greater symptomatic complaint and impaired psychological well-being.
      Relatives also reported a poorer quality of life in the hypertensive subjects.
      This impairment could be a result of the disease, adverse effects of drug
      treatment or to the effects of labelling.

PMID- 8746644
TI  - Results of long-term medical treatment of patients with arterial hypertension
      complicated by aortic dissection.
AB  - The purpose of the study was to analyse results of ambulatory treatment of
      patients with arterial hypertension complicated by aortic dissection. Twenty
      patients (19 men, one woman), aged between 39 and 72 years, underwent full
      physical examination. In all cases the diagnosis of aortic dissection was
      confirmed by at least two different imaging methods (ultrasonography, digital
      subtractional angiography, computer tomography or nuclear magnetic resonance).
      During follow-up (3-75 months, mean 34.3 months), physical examination was
      performed every 6-8 weeks, chest radiograph was taken once a year. All patients
      controlled their blood pressure (BP) at home. According to the mean number of in
      home BP measurements per month all patients were divided into two groups: group I
      good (n = 10) and group II bad compliers (n = 10) (28 +/- 30 vs 3 +/- 2 in-home
      BP measurements a month). Ten patients (6 in group I, 4 in group II) underwent 24
      h automatic BP measurement examination. Blood samples were collected for serum
      cholesterol and uric acid measurements. All patients suffered from arterial
      hypertension and in five cases at least one parent suffered from this disease.
      Only three of 20 have never smoked cigarettes. Elevated serum cholesterol was
      observed in 10 (50%) cases and elevated uric acid in six (30%). Proximal (type A)
      aortic dissection (DeBakey classification type I and II) was found in 13
      patients, distal aortic dissection (type B) in seven patients. All patients were
      treated with beta-blockers. In 75% of 20 cases three or more hypotensive drugs
      were used simultaneously to control BP. In the group I lower values of mean of
      maximal SBP (160 +/- 10 vs 177 +/- 7 mm Hg, P < 0.05) and lower mean circadian
      heart rate (58.6 +/- 7.5 vs 80.9 +/- 7.9 beats/min, P < 0.005) were observed. The
      most frequent complaints were intermittent claudication, 9 (45%); angina pectoris
      8 (40%), other chest pain, 4 (20%). During follow-up period (3-75 months, mean
      34.3 months) five of 20 patients (25%) died (all had proximal, type A dissection)
      and 15 of 20 patients (75%) are still alive. All deaths in group II were sudden,
      whereas the only one in group I was because of chronic renal insufficiency.
      Mortality rate in the two groups were 10% (one of 10) vs 40% (four of 10),
      respectively, in groups I and II. IN CONCLUSION: patients who control their BP
      more often have the lower values as well as lower heart rate and therefore a
      better prognosis.

PMID- 8746645
TI  - What method should be used to define 'night' when assessing diurnal systolic
      blood pressure variation in the elderly?
AB  - Diurnal blood pressure (BP) variation can be assessed by cusums-derived measures
      and by the day-night BP difference from time-, activity- and diary-defined
      'night' periods. Reproducibility of diurnal systolic BP (SBP) variation by these
      different methods was studied in 19 active elderly normotensives, mean age 68.5
      years. Subjects underwent simultaneous 24 h BP (Spacelabs 90207) and activity
      (Gaehwiler wrist actigraph) monitoring on two occasions (median interval 70
      days). On the first occasion, mean diurnal SBP variation was 15.1 +/- 8.1 mm Hg
      by fixed-time definition of 'night' (22.07). When compared with 22-07 defined
      'night' period, actigraph- and diary-defined 'night-time' was significantly
      reduced (-60 +/- 49, and -48 +/- 51 min, respectively) and consequently diurnal
      SBP variation was significantly greater at 18.2 +/- 8.1 mm Hg and 17.6 +/- 8.4 mm
      Hg, respectively. Actigraph recordings were also used to exclude 'night' BP
      readings associated with activity, but this did not significantly alter the
      diurnal SBP variation. Cusums-derived circadian alteration magnitude resulted in
      the greatest value for SBP variation (23.4 +/- 6.7 mm Hg). However,
      reproducibility of diurnal SBP variation was poor by fixed-time method with a
      coefficient of variation (CV) of > 50%, and only improved to 40% with diary use.
      Actigraph measurements, even if used to exclude BP values associated with
      disturbed sleep, did not improve this further. Cusums-derived measures of diurnal
      variation slightly improved reproducibility with a CV of 34.6% and may be a
      better method in the assessment of diurnal BP variation in the elderly.

PMID- 8746647
TI  - Factors predisposing cancer patients to infection.

PMID- 8746648
TI  - Signs and symptoms of infections and differential diagnosis from noninfectious
      conditions.

PMID- 8746649
TI  - Chemoprophylaxis for the prevention of bacterial and fungal infections.

PMID- 8746650
TI  - Infection control for oncology.

PMID- 8746651
TI  - Empiric therapy for bacterial infections in neutropenic patients.

PMID- 8746652
TI  - New antifungal compounds and strategies for treatment of invasive fungal
      infections in patients with neoplastic diseases.

PMID- 8746653
TI  - Herpesvirus infections in immunocompromised patients.

PMID- 8746654
TI  - New and unusual infections in neutropenic patients.
AB  - Infections in immunocompromised patients with cancer are common and the primary
      risk factor is neutropenia, usually induced by chemotherapeutic agents. The
      spectrum of bacterial infection is shifting from gram-negative to gram-positive.
      The array of fungal infections in cancer patients is expanding to include
      organisms previously unknown as invasive human pathogens. New species are being
      defined to explain extant pathologies, and free living algae are now emerging as
      pathogens in immunocompromised patients. Physicians must remain alert to these
      emerging pathogens and to the need to evaluate optimal treatments for the usual
      and unusual infections in neutropenic and other compromised patients with cancer
      and allied diseases.

PMID- 8746655
TI  - Pneumonia in cancer patients.

PMID- 8746656
TI  - Intravascular device-related infections in cancer patients.

PMID- 8746657
TI  - Indications for intensive care in the management of infections in cancer
      patients.

PMID- 8746658
TI  - Colony-stimulating factors: current applications and perspectives.

PMID- 8746659
TI  - Drug interaction and pharmacological considerations during anti-infective therapy
      in cancer patients.

PMID- 8746660
TI  - Cytoskeleton, cellular signals, and cytoplasmic localization in Chaetopterus
      embryos.

PMID- 8746661
TI  - Cytoskeleton and ctenophore development.

PMID- 8746662
TI  - Sea urchin microtubules.

PMID- 8746663
TI  - Actin-membrane cytoskeletal dynamics in early sea urchin development.

PMID- 8746664
TI  - RNA localization and the cytoskeleton in Drosophila oocytes.

PMID- 8746665
TI  - Role of the actin cytoskeleton in early Drosophila development.

PMID- 8746666
TI  - Role of the cytoskeleton in the generation of spatial patterns in Tubifex eggs.

PMID- 8746667
TI  - Development and evolution of an egg cytoskeletal domain in ascidians.

PMID- 8746668
TI  - Remodeling of the specialized intermediate filament network in mammalian eggs and
      embryos during development: regulation by protein kinase C and protein kinase M.
AB  - The sheets serve as an maternal supply of assembled, cytokeratin, intermediate
      filaments. They are remodeled at each major developmental transition in mammalian
      early development, that is fertilization, embryonic compaction, blastocyst
      formation, and formation of the primitive ectoderm and primitive endoderm during
      implantation into the uterine wall. Our results indicate that the sheets exist as
      specialization for placental development as they have a major role in the
      maintenance of epithelial integrity at the time the embryo is implanting into the
      uterine wall. They also contribute intermediate filaments to the junctional
      complexes required for embryonic compaction. Our analyses demonstrate the they
      are regulated at the time of fertilization by the action of PKC/PKM, a kinase
      that acts as a cellular chronometer with both temporal and spatial precision that
      remodels the egg into the zygote.

PMID- 8746669
TI  - Mammalian model systems for exploring cytoskeletal dynamics during fertilization.

PMID- 8746670
TI  - Cytoskeleton in teleost eggs and early embryos: contributions to cytoarchitecture
      and motile events.

PMID- 8746671
TI  - Confocal immunofluorescence microscopy of microtubules, microtubule-associated
      proteins, and microtubule-organizing centers during amphibian oogenesis and early
      development.

PMID- 8746672
TI  - Cortical cytoskeleton of the Xenopus oocyte, egg, and early embryo.

PMID- 8746674
TI  - Fundamentals of capillary electrophoresis theory.

PMID- 8746673
TI  - Intermediate filament organization, reorganization, and function in the clawed
      frog Xenopus.

PMID- 8746675
TI  - Standard commercial instrument description.

PMID- 8746676
TI  - Typical operating procedures.

PMID- 8746677
TI  - Method development/optimization.

PMID- 8746678
TI  - Quantitation procedures.

PMID- 8746679
TI  - Optimization of precision in quantitative analysis.

PMID- 8746680
TI  - Optimization of sensitivity.

PMID- 8746681
TI  - Method validation.

PMID- 8746682
TI  - Fraction collection.

PMID- 8746683
TI  - Troubleshooting.

PMID- 8746684
TI  - Quick guide to running a successful separation.

PMID- 8746685
TI  - Micellar electrokinetic chromatography.

PMID- 8746686
TI  - Capillary gel electrophoresis.

PMID- 8746687
TI  - Chiral separations by capillary electrophoresis.

PMID- 8746688
TI  - Capillary electrochromatography.

PMID- 8746689
TI  - Application and limits of sample stacking in capillary electrophoresis.

PMID- 8746690
TI  - Analysis of bases, nucleosides, and (oligo)nucleotides by capillary
      electrophoresis.

PMID- 8746691
TI  - Application of capillary electrophoresis to pharmaceutical analysis.

PMID- 8746692
TI  - Separation of peptides and protein digests by capillary electrophoresis.

PMID- 8746693
TI  - Additional application areas of capillary electrophoresis.

PMID- 8746694
TI  - Lymphocyte subset abnormalities in German shepherd dog pyoderma (GSP).
AB  - Peripheral blood lymphocyte subpopulations were studied in 12 German shepherd
      dogs suffering from deep pyoderma (GSP). Twelve other healthy but matched dogs
      were used as controls. GSP was found to be associated with an imbalance in the
      CD4 and CD8 subsets (respectively 37.3 +/- 8.7% and 28.6 +/- 6.6%, as compared to
      47.5 +/- 8.8% and 19.3 +/- 4.0% in the controls). The activation markers were not
      affected by GSP. Moreover, analysis of the B-cell populations showed a striking
      decrease in the level of CD21 cells (5.5 +/- 3.3% of CD21+ lymphocytes, compared
      to 12.2 +/- 6.0 in the controls). This study suggests that the immunological
      imbalance observed in GSP may be associated with defective helper cells, and
      provides further evidence that dogs suffering from GSP are not immunologically
      normal reactors.

PMID- 8746695
TI  - Cellular immunity in dogs with keratoconjunctivitis sicca before and after
      treatment with topical 2% cyclosporine.
AB  - Peripheral cellular immunity of ten dogs with keratoconjunctivitis sicca (KCS)
      that had not been treated with topical corticosteroids or cyclosporine was
      evaluated (by use of in vitro lymphocyte proliferation assays and CD4+/CD8+
      lymphocyte subset analysis) before and after 1 and 3 months of treatment with
      topical ocular 2% cyclosporine (CsA). In vitro lymphocyte proliferation and
      CD4+/CD8+ lymphocyte subset analysis was done in eight normal dogs at the 0, 1
      and 3 month time periods to use for comparison. There was no significant
      difference in lymphocyte proliferation or numbers of CD4+ or CD8+ lymphocytes in
      dogs with KCS and normal dogs prior to CsA treatment. However, by 1 month's time,
      lymphocyte proliferation had decreased in the CsA-treated Dogs with KCS, and by 3
      months there was a significant difference (P < 0.0001) from the normal dogs.
      These results suggest that dogs with KCS may not have altered peripheral cellular
      immunity and that use of topical 2% cyclosporine for treatment of KCS causes a
      suppression of lymphocyte proliferation after 1 to 3 months of use.

PMID- 8746696
TI  - Prospective characterization of the clinicopathologic and immunologic features of
      an immunodeficiency syndrome affecting juvenile llamas.
AB  - The clinicopathologic and immunologic features of 15 llamas affected with
      juvenile llama immunodeficiency syndrome (JLIDS) are described. Healthy adult (n
      = 10) and juvenile (n = 10) llamas served as controls. JLIDS llamas were
      characterized by wasting, and clinically apparent, repeated infections were
      frequently observed. The median age at which a health problem was first perceived
      was 11.6 months. All 15 affected llamas died or were killed, and JLIDS was
      confirmed at necropsy. The median duration of illness was 3.5 months. Lymphocyte
      blastogenesis assays showed suppressed responses (particularly to Staphylococcus
      sp. Protein A) in JLIDS llamas. No evidence of retroviral infection was detected.
      Mild, normocytic, normochromic, non-regenerative anemia, low serum albumin
      concentration and low to low-normal globulin concentrations were typically found
      on initial clinical evaluation. Lymph node biopsies showed areas of paracortical
      depletion. All llamas affected with JLIDS had low serum IgG concentrations, pre
      vaccination titers against Clostridium perfringens C and D toxoids of < or =
      1:100, and no titer increase following vaccination.

PMID- 8746697
TI  - Effect of passively administered immunoglobulin G on the colonization and
      clearance of Bordetella avium in turkeys.
AB  - This study was conducted to detect the effect of parenterally administered
      immunoglobulin isotype G (IgG) on the colonization and clearance of Bordetella
      avium at the tracheal surface in young turkeys. In two separate experiments, 3
      week-old turkeys were infected with B. avium either after or before IgG
      administration. Comparisons were made between a control group which received an
      irrelevant IgG (specific for keyhole limpet hemocyanin [KLH]) and the
      experimental group which received a B. avium-specific IgG. When given before the
      bacteria, IgG reduced the numbers of colony-forming units (CFUs) in the trachea.
      As a supplement to non-specific respiratory defense mechanisms, B. avium-specific
      IgG also appears to inhibit colonization of the tracheal mucosa. In a second
      experiment designed to study the role of IgG in bacterial clearance,
      administration of B. avium-specific IgG after bacterial inoculation significantly
      reduced the number of CFUs on the tracheal surface. These studies support the
      role of B. avium-specific IgG in resistance to and recovery from B. avium
      infection.

PMID- 8746698
TI  - Effect of stress on interleukin-2 receptor expression by bovine mononuclear
      leukocytes.
AB  - Holstein calves given three consecutive i.m. injections of dexamethasone (DEX)
      (0.04 mg kg-1) showed lymphopenia and neutrophilia with increased numbers of
      mature neutrophils on post-injection Days 1 and 2, but these values returned to
      normal levels by post-injection Day 3. Interleukin-2 receptor (IL-2R) expression
      by peripheral blood mononuclear cells (PBMC) was evaluated by flow cytometry
      using a monoclonal antibody specific for bovine IL-2R alpha. Treatment with DEX
      significantly decreased expression of IL-2R alpha in Concanavalin A (Con A)
      activated PBMC on Day 1 (P < 0.02) and on Day 2 (P < 0.1). On Day 3, expression
      of IL-2R alpha by PBMC was similar in control and DEX-treated calves. This
      decrease in IL-2R alpha expression correlated with decreased proliferative
      responses of PBMC to the T-cell mitogens, phytohemagglutinin (PHA) and Con A.
      Following in vitro treatment with recombinant human (rhu) interleukin-12 (IL-12)
      Con A-induced proliferative responses of PBMC tended to be higher in both groups.
      However, the rhu IL-12 induced increase of Con A activated proliferative
      responses were significantly greater in DEX-treated calves than in control
      calves. IL-2R alpha expression by PBMC was found to be less in calves transported
      800 km in a truck as compared to that in PBMC from controls. These data suggest
      that stress-induced immunosuppression in calves may involve decreased IL-2R alpha
      expression and decreased IL-12 production. Serum chemistry results indicated a
      trend toward higher creatine kinase (CK) levels in DEX-treated calves. This may
      be due to the lysis of corticosteroid sensitive lymphocytes.

PMID- 8746699
TI  - Alveolar mastocytosis and eosinophilia in lambs with naturally acquired nematode
      infections of Protostrongylus rufescens and Haemonchus contortus.
AB  - Specific-pathogen-free Dorset and St. Croix lambs were placed on pasture
      contaminated with Haemonchus contortus third stage larvae and slugs carrying
      third stage larvae of Protostrongylus rufescens for an entire grazing season to
      evaluate breed differences in acquired resistance to these nematodes. Lambs were
      evaluated for clinical signs, clinical pathology and histopathologic lesions
      associated with these infections. Both breeds acquired natural infections with H.
      contortus and lungworm when allowed to graze contaminated pastures for 5 months
      during the summer and fall in central Maryland. Dorset sheep maintained heavy
      abomasal worm burdens of H. contortus throughout the grazing period when compared
      to St. Croix breed sheep. Seven of 12 Dorset sheep and three of 12 St. Croix
      sheep on pasture acquired heavy lungworm infections after at least 15 weeks of
      exposure, as evidenced by shedding of first stage larvae in feces and numerous
      subpleural lung lesions containing adult P. rufescens found at necropsy. All
      lungworm infected animals had mild respiratory and gastrointestinal signs, and
      two of five Dorset sheep with both infections had chronic anemia. All lungworm
      and H. contortus infected Dorset sheep had decreased numbers of circulating white
      blood cells. There was mastocytosis in the lungs of lungworm infected Dorset and
      St. Croix sheep when compared to age- and breed-matched control sheep prevented
      from acquiring both lungworm and trichostrongyle infections. No difference was
      noted in the number of mast cells in the abomasum, duodenum and skin of infected
      and non-infected Dorset sheep. A morphologic range of mast cell forms was
      observed in the lungs of infected sheep including transitional cells and globular
      leukocytes. The number of eosinophils was significantly greater in the lungs but
      not in the abomasum of infected sheep. Despite the pronounced cellular
      infiltrates surrounding the adult lungworms, they were viable on recovery and
      appeared undamaged when examined histologically.

PMID- 8746700
TI  - Enhanced production of bovine tumor necrosis factor-alpha during the
      periparturient period.
AB  - This study examined the production of tumor necrosis factor (TNF-alpha) by
      mononuclear cells isolated from peripheral blood and supramammary lymph nodes of
      periparturient and mid to late lactating dairy cows. Monocyte-enriched cell
      populations were stimulated with lipopolysaccharide (LPS) and analyzed for TNF
      alpha concentrations. Flow cytometric analysis was performed to determine the
      frequencies of relevant cell populations. Isolated mononuclear cells from
      periparturient dairy cows produced significantly higher levels of TNF-alpha than
      mid to late lactating dairy cows regardless of tissue location. A corresponding
      increase in the frequency of monocytes also was observed in tissue samples
      obtained from periparturient animals. The higher proportion of monocytes capable
      of producing TNF-alpha in the periparturient dairy cow may account for the
      increased levels of this potent mediator. Within the periparturient period,
      peripheral blood mononuclear cells were found to produce significantly less TNF
      alpha than cells isolated from mammary lymph nodes. However, flow cytometric
      analysis revealed similar monocyte concentrations in both the peripheral blood
      and mammary lymph node. This indicates that the differences in cytokine
      production may be due to variations in monocyte activation state with respect to
      tissue location. It is possible that greater potential to produce TNF-alpha
      during the periparturient period may contribute to the severe acute phase
      response of the mammary gland to coliform infections during this time. Limiting
      TNF-alpha production by monocytes, particularly within the mammary gland, may
      reduce the severity of clinical coliform mastitis in periparturient dairy cattle.

PMID- 8746701
TI  - Morphometric analysis of CD4+, CD8+, and gamma/delta+ T-lymphocytes in lymph
      nodes of cattle vaccinated with Brucella abortus strains RB51 and 19.
AB  - T-lymphocyte subpopulations were examined in vivo by computer-assisted
      morphometry of superficial cervical lymph nodes of cattle vaccinated with
      Brucella abortus. Twenty-four 8-month-old Hereford heifers were injected
      subcutaneously in the axillary area with 1 x 10(10) live B. abortus strain RB51
      (SRB51, n = 12) or strain 19 (S19, n = 6) suspended in 2 ml of saline. Six
      control heifers were injected with sterile saline. Lymph nodes were collected at
      1, 2, 4, 6, 10 and 12 weeks postvaccination. Both SRB51 and S19 were cultured
      from lymph nodes, but SRB51 persisted for a longer period after vaccination (10
      weeks) than S19 (6 weeks). Cryostat sections were incubated with monoclonal
      antibody to CD4 (IL-A11), CD8 (IL-A51), or gamma/delta (IL-A29) bovine T-cell
      surface antigen and processed for immunoperoxidase staining. Numbers of stained
      lymphocytes in randomly selected fields were calculated using image-analysis
      software. There were no significant differences in the number (P = 0.07) or
      relative proportions (P = 0.22) of CD4+, CD8+, and gamma/delta+ lymphocytes in
      SRB51, S19, and control lymph nodes. There was a statistically significant
      difference in the distribution of the three T-cell subsets (P = 0.001). The CD4+
      cells were most closely grouped and the gamma/delta+ cells had the most widely
      scattered distribution, regardless of vaccination status. The results support
      other studies indicating lymphocyte depletion is not a sequela of infection with
      B. abortus vaccine strains given to conventionally reared cattle.

PMID- 8746702
TI  - A comparison of beam-hardening artifacts in x-ray computerized tomography with
      gadolinium and iodine contrast agents.
AB  - Lanthanide-based compounds such as Gd-DTPA are currently used as contrast agents
      in MRI. Recent experiments using CT and transmission radiography show that Gd
      agents can increase image contrast by up to a factor of 2 relative to more
      commonly used iodinated agents on an equi-molar basis. It has also been suggested
      that beam hardening artifacts may be reduced with Gd. This hypothesis was
      experimentally tested on three different CT scanners using a circular water
      equivalent phantom with contrast filled tube inserts. It was found that the
      artifacts were a factor of 1.3-1.8 more pronounced with the iodinated contrast
      compared with Gd-DTPA. A theoretical model which uses an experimentally derived
      photon energy spectrum is proposed which relates the strength of beam hardening
      artifacts to the variance (over the energy spectrum) of the attenuation
      coefficient of the contrast agent. This allows easy assessment of the relative
      magnitudes of the artifact for different contrast agents.

PMID- 8746703
TI  - X-ray imaging using amorphous selenium: photoinduced discharge (PID) readout for
      digital general radiography.
AB  - Digital radiographic systems based on photoconductive layers with the latent
      charge image readout by photoinduced discharge (PID) are investigated
      theoretically. Previously, a number of different systems have been proposed using
      sandwiched photoconductor and insulator layers and readout using a scanning laser
      beam. These systems are shown to have the general property of being very closely
      coupled (i.e., optimization of one imaging characteristic usually impacts
      negatively on others). The presence of a condensed state insulator between the
      photoconductor surface and the readout electrode does, however, confer a great
      advantage over systems using air gaps with their relatively low breakdown field.
      The greater breakdown field of condensed state dielectrics permits the
      modification of the electric field during the period between image formation and
      image readout. The trade-off between readout speed and noise makes this system
      suitable for instant general radiography and even rapid sequence radiography,
      however, the system is unsuitable for the low exposure rates used in fluoroscopy.

PMID- 8746704
TI  - Spatial and temporal analysis of human motor activity using noninvasive NIR
      topography.
AB  - The effect of motor activity on the left fronto-central region of the human brain
      was analyzed spatially and temporally by using noninvasive near-infrared light
      (NIR) topography. The changes in oxygenation states caused by motor activity were
      measured using intensity-modulated NIR spectroscopy at ten measurement positions
      on the head surface. The subject randomly performed unilateral finger opposition
      for 30 s as motor stimulation. When the subject performed contralateral (right)
      finger movement, significant increases in both oxygenated hemoglobin (oxy-Hb) and
      total hemoglobin (total-Hb) and decreases in deoxygenated hemoglobin (deoxy-Hb)
      were observed in a particular area. By mapping the static topograms of the
      changes of each Hb and comparing them with an anatomical image of MRI, it was
      found that the particular area was located on the motor cortex along the central
      sulcus. By mapping the dynamic topograms of the changes of total-Hb, which
      reflect the cerebral blood volume, and analyzing the spatiotemporal hemodynamic
      changes associated with the brain activity, it was found that the regional change
      in cerebral blood volume in the primary motor area overlaps the global change
      around the motor cortex. These results demonstrate that NIR topography can be
      used to effectively observe the human brain activity.

PMID- 8746705
TI  - A K edge filter technique for optimization of the coherent-to-Compton scatter
      ratio method.
AB  - The ratio method involves forming the ratio of the elastic to inelastic x-ray
      scatter signals from a localized region of a scattering medium to determine its
      mean atomic number. An analysis is presented of two major error sources
      influencing the ratio method: firstly statistical (photon) noise and secondly
      multiple scattering and self-attenuation of the primary and scatter radiations in
      the medium. It is shown that a forward scattering geometry minimizes errors of
      both types for substances composed of elements with low and medium atomic number.
      However, owing to the small energy separation (approximately 100 eV) of coherent
      and Compton scatter for this geometry, they cannot be distinguished directly with
      semiconductor (e.g., Ge) detectors. A novel K edge filter technique is described
      which permits separation of the elastic and Compton signals in the forward
      scatter geometry. The feasibility of this method is demonstrated by experimental
      results obtained with Ta fluorescence radiation provided by a fluorescent x-ray
      source filtered with an Er foil. The extension of this technique to the "in vivo"
      measurement of low momentum transfer inelastic scattering from biological
      tissues, possibly providing useful diagnostic information, is briefly discussed.

PMID- 8746706
TI  - Multiwindow scatter correction techniques in single-photon imaging.
AB  - We studied the performance of linear scatter correction methods for single-photon
      imaging with Tc-99m and Tl-201, using a numerical model of the Rollo phantom and
      measurements with a gamma camera modified to record position and energy
      information in list mode form. We compared the performance of these methods to
      per-image optimized linear methods and to locally adaptive linear methods, and
      developed estimates of the limits on accuracy of scatter correction imposed by
      the presence of Poisson noise. For both Tc-99m and Tl-201 imaging at a fixed
      depth, particularly at low count rates, the performance of dual-window methods,
      or of adaptive methods, is near the best possible for linear methods. Smoothing
      of the scatter estimate results in minor improvement for Tl-201. Substantial gaps
      between the performance of any of these linear methods and the limits imposed by
      Poisson noise remain and are due primarily to bias, with the gap for Tl-201 being
      larger than that for Tc-99m.

PMID- 8746707
TI  - Figures of merit (FOMs) for imaging and therapy using monoclonal antibodies.

PMID- 8746708
TI  - Evaluation of electronic portal imaging device for missing tissue compensator
      design and verification.
AB  - The purpose of this investigation is to determine if electronic portal imaging
      devices (EPIDs) can be used for the design and verification of compensating
      filters. In order to do this, we investigated the operating characteristics of a
      commercially available EPID and the variation in transmitted dose for various
      measurement situations. We performed four initial tests to determine the EPID
      response specific to compensator situations. The tests determined EPID response
      to variable patient SSDs, different gantry angles, positions of an inhomogeneity
      within a phantom, and the sensitivity variation of different parts of the imager.
      After these tests, we determined the attenuation functions relating EPID response
      to phantom thickness for various phantom materials. With these functions, we
      tested simple compensation situations to demonstrate that missing tissue
      compensators can both be designed and verified using EPIDs.

PMID- 8746709
TI  - Accounting for the variation in collision kerma-to-terma ratio in polyenergetic
      photon beam convolution.
AB  - In photon beam convolution, the distribution of energy deposition about a primary
      photon interaction site due to charged particles set in motion at that site is
      represented by the primary kernel. Energy deposited due to scattered photons,
      bremsstrahlung, and annihilation photons is represented by the scatter kernel. As
      the energy deposited in each kernel voxel is normalized to the energy imparted at
      the interaction site, it is known as a fractional energy distribution. In terma
      based convolution, where kernels are normalized to total energy imparted at the
      interaction site and are convolved with the terma in the dose calculation
      process, the sum of fractional energies contained in the primary kernel is equal
      to the ratio of collision kerma (Kc) to terma (T) corresponding to the energy
      spectrum used to generate the kernel. Since the ratio of collision kerma to terma
      increases with depth as the beam hardens, the integral fractional energy in a
      primary kernel formed for the spectrum at the surface is less than the ratio Kc/T
      at depth. This causes primary dose to be increasingly underestimated with depth
      and scatter dose to be increasingly overestimated. Single polyenergetic
      convolution (using polyenergetic primary and scatter kernels formed using a
      polyenergetic primary photon spectrum) is thus not as rigorous as if a separate
      convolution is performed for each energy component. The ratio of true primary
      dose to single polyenergetic primary dose increases almost linearly with depth
      and is almost equal to the Kc/T ratio. Primary and scatter dose are calculated
      correctly if a single polyenergetic convolution is performed in terms of Kc (for
      primary) and T-Kc (for scatter), where the kernels are weighted sums of
      monoenergetic kernels normalized to Kc and T-Kc. With this method, it is ensured
      that total primary energy deposited due to primary photon interactions in a unit
      mass at a point is equal to Kc at that point.

PMID- 8746710
TI  - Analytical representation of head scatter factors for shaped photon beams using a
      two-component x-ray source model.
AB  - An analytic representation proposed for the relative intensity distribution of
      the extra-focal source in a two-component x-ray source model serves as the basis
      for calculation. From this representation, a closed-form expression for head
      scatter factors defined on the central beam axis is derived by integrating over
      the area of the extra-focal source plane visible from the measurement point. The
      resulting expression is applicable to photon beams from different Varian
      accelerators and different photon energies, and includes effects arising from
      beam shaping with cerrobend blocks or multileaf collimators (MLCs). For 6- and 15
      MV photon beams from Varian 600 C and 2300 CD accelerators (Varian Oncology
      Systems, Palo Alto, CA), 361 measured head scatter factors for square,
      rectangular, asymmetric, and arbitrarily shaped fields, formed by either the X
      and Y jaws, the MLC and Y jaws, or by the MLC alone, were compared with model
      calculations. Results show that 93.4% of calculated values match corresponding
      experimental points to within 0.5%, the average deviation being 0.23% and the
      maximum deviation 0.9%. Thus, as a consequence of this work, the different
      influence of the X jaws, the Y jaws, and the MLC on head scatter factors is
      quantitatively described. In particular, it is demonstrated that in the case of
      radially symmetric scattering, the collimator exchange effect arises as a result
      of the different distances of the X and Y jaws from the focal spot.

PMID- 8746711
TI  - Comparative Ngas measurements for a parallel plate chamber in proton, electron,
      and 60Co beams.
AB  - The TG21 protocol introduced the Ngas calibration method for parallel plate
      chambers in high-energy electron beams. This calibration method was performed for
      a Markus parallel plate chamber in proton and electron beams of various energies
      as well as a 60Co beam. For an individual chamber, the Ngas value in proton beams
      differs from the Ngas value in cobalt and electron beams by the ratio of (W/e)
      for proton beams to that of a 60Co beam. While the replacement correction factor
      is essential for Markus chambers in low-energy electron beams, the results of our
      Nppgas measurements in proton beams showed that the Markus chamber does not need
      a replacement correction factor for therapeutic proton beams of energy 20-170
      MeV. These results indicate that the 0.7-mm guard ring of the Markus chamber is
      adequate to prevent the in-scattering of secondary electrons produced by proton
      irradiation of the chamber wall or medium.

PMID- 8746712
TI  - Extrafocal radiation: a unified approach to the prediction of beam penumbra and
      output factors for megavoltage x-ray beams.
AB  - An extrafocal source model has been developed to explain the dependence of head
      scatter and beam penumbra on field size. In this model, the x-ray source of a
      medical linear accelerator is described by two components: a small but intense
      focal component; and a broadly distributed extrafocal component of low intensity.
      The extrafocal component is so large that it can be "eclipsed" by the field
      defining collimators. Extrafocal radiation was found to account for 12% of the
      energy fluence on the central axis of the 6 MV x-ray beam from a Varian Clinac
      2100 c accelerator. Head scatter factors were calculated "in-air" for symmetric,
      asymmetric, and half-blocked fields. Calculations agreed with measured values to
      better than 0.5%, on average. However, head scatter factors for asymmetric fields
      were underestimated by 1.2% when one of the field dimensions was reduced to 4 cm
      (the minimum jaw setting that was tested). The extrafocal source model was
      combined with a convolution/superposition dose calculation algorithm to calculate
      dose-per-monitor-unit calibration (output) factors and beam dose profiles in
      water. These dose calculations predict the degradation of the field edge as a
      function of field size, and calculate output factors to within 0.5%, on average.
      In the most extreme case of a 4 cm field width, output factors were
      underestimated by 2%. Dose profiles are predicted without the aid of an empirical
      fit to measured beam penumbra data. The extrafocal source model will be
      particularly useful for fields defined by independent jaw and multileaf
      collimation systems.

PMID- 8746713
TI  - Effects of scatter generated by beam-modifying absorbers in megavoltage photon
      beams.
AB  - Transmission through a beam-modifying absorber consists of attenuated primary
      beam and scattered radiation generated by the absorber. The primary component of
      the transmitted beam is characterized by the narrow beam attenuation coefficient
      which depends upon the energy of the beam and type of the absorber. In addition
      to beam energy and absorber material, the scatter component also depends on field
      size, thickness and shape of the absorber, location of the absorber with respect
      to the source, and the point of calculation. Based upon Compton first-scatter, a
      method has been developed to calculate effective broad beam transmission through
      any arbitrarily shaped absorber with variable thickness for any points on and off
      the central axis. The method requires predetermined narrow beam attenuation
      coefficients as a function of thickness. Transmission calculations for various
      absorbers such as wedges and attenuators were performed for cobalt-60 and 6-MV
      beams and were compared with measured data. For a cobalt-60 beam, the measured
      transmission fraction through a 1.33-cm-thick absorber (alloy, consisting of 55%
      bismuth and 45% lead) for a field size of 24 x 24 cm2 is 17% higher than the
      calculated value using a narrow beam attenuation coefficient. Also, for the same
      absorber, measured central axis transmission is as much as 3.6% higher compared
      to off-axis locations. The measured transmission fraction through a 1.33-cm
      absorber was found to differ by as much as 13% and 14% for Cobalt-60 and 6 MV,
      respectively, as the chamber-to-source distance was varied from 70 to 110 cm. The
      agreement between calculated and measured values is within 0.5% for both energies
      whereas conventional narrow beam calculations would have yielded errors of 18%
      and 19%, respectively. Similar agreement was obtained when comparing calculated
      and measured wedge factors as a function of field size, with the maximum
      deviation being 0.7%. Measured scattered doses, due to an attenuator covering
      part of a beam, show a maximum for a thickness of approximately one mean-free
      path. This is also predicted by calculations with an agreement of 0.3%.

PMID- 8746714
TI  - A direct approach for the determination of absorbed dose from electron beams
      using non-water phantoms.
AB  - Non-water solid phantoms are often used in the determination of absorbed dose to
      water for electron beams. Protocols have been established and widely accepted. In
      these procedures, several assumptions in addition to the Spencer-Attix conditions
      are required, and several correction factors are needed. A direct approach, in
      which the conversion is carried out in a single step using a modified Spencer
      Attix formula, is studied in this paper. The approach is consistent with the
      protocols for water phantom, and the conversion factors can be calculated using
      Monte Carlo simulation. The behavior of the conversion factors is described by
      comparing the results from the AAPM protocol and experiment data for three
      electron energies (6, 12, and 16 MeV). This study demonstrates that for beam
      calibration at dmax, the results from the new approach agree with those from the
      protocol with a maximum discrepancy of 1% for PMMA and 1.3% for polystyrene. For
      the depth dose measurement from near the surface to R80, the agreement is within
      1.5% for PMMA, 2.5% for polystyrene, and 2.8% for electron solid water. It also
      demonstrates that for electron solid water, the new approach provides better
      agreement with experiment data for the beam calibration at d(max).

PMID- 8746715
TI  - Effective SSD for electron beams as a function of energy and beam collimation.

PMID- 8746716
TI  - White polystyrene as a substitute for water in high energy photon dosimetry.
AB  - White polystyrene (C8H8 with 2 wt. % to TiO2) has been compared to water using
      photon beams with nominal accelerating potential of 4 MV, 6 MV, 15 MV and 25 MV.
      The absolute reading and hence the measured absorbed dose is found to be up to 3%
      lower in white polystyrene which can be taken into account by using a correction
      factor. From these data differences in relative measurements (TMR or percentage
      depth dose) can be calculated showing differences of less than 0.7% normalized to
      maximum dose. Since the correction factor shows a dependence on photon energy and
      field size the use of a common scaling factor is not possible. The effect on
      photon dosimetry is discussed.

PMID- 8746717
TI  - A scintillating fiber beam-energy monitor for electron beam therapy.
AB  - A new type of beam-energy monitor is described, which has been developed to check
      the energies of electron beams from radiotherapy accelerators. The monitor
      consists of a pair of scintillating fibers and photodiode read-out circuits that
      measure the energy dependence of electron transmission through a wedge-shaped
      absorber. A linear energy response and 1% accuracy for energy constancy
      measurements are attained with the monitor. The monitor having advantages of
      simple mechanical and electronic constructions, small size, and low cost is
      suitable for practical use as a portable device.

PMID- 8746718
TI  - An international neutron dosimetry intercomparison.

PMID- 8746719
TI  - Double-film technique for the determination of the homogeneity of line sources.
AB  - A new technique is presented for determining the homogeneity of the linear
      activity. The method uses two x-ray films that are firmly pressed against
      opposing sides of a needle containing a radioactive line source. The homogeneity
      of the linear activity of 68 iridium-192 wires has been measured. About 80% of
      the measured linear activities showed deviations of no more than 5% from the
      mean; about 20% of the measured linear activities showed deviations of 5%-10%
      from the mean. Individual wires may contain deviations of 5% or more extended
      over several centimeters, which causes the dose in the prescription point to
      deviate 5% from the desired value. Four wires (8%) were rejected for this reason.

PMID- 8746720
TI  - Comparison of proton and x-ray conformal dose distributions for radiosurgery
      applications.
AB  - Highly focused dose distributions for radiosurgery applications are successfully
      achieved using either multiple static high-energy particle beams or multiple-arc
      circular x-ray beams from a linac. It has been suggested that conformal x-ray
      techniques using dynamically shaped beams with a moving radiation source would
      offer advantages compared to the use of only circular beams. It is also thought
      that, generally, charged particle beams such as protons offer dose deposition
      advantages compared to x-ray beams. A comparison of dose distributions was made
      between a small number of discrete proton beams, multiple-arc circular x-ray
      beams, and conformal x-ray techniques. Treatment planning of a selection of
      radiosurgery cases was done for these three techniques. Target volumes ranged
      from 1.0-25.0 cm3. Dose distributions and dose volume histograms of the target
      and surrounding normal brain were calculated. The advantages and limitations of
      each technique were primarily dependent upon the shape and size of the target
      volume. In general, proton dose distributions were superior to x-ray
      distributions; both shaped proton and shaped x-ray beams delivered dose
      distributions which were more conformal than x-ray techniques using circular
      beams; and the differences between all proton and x-ray distributions were
      negligible for the smallest target volumes, and greatest for the larger target
      volumes.

PMID- 8746721
TI  - Dosimetric characterization of radiosurgical beams with a diamond detector.
AB  - Dosimetric characteristics of small diameter 6 MV photon beams for a commercial
      radiosurgery system have been measured in a solid water phantom with a new
      diamond detector and compared with measurements using a p-type Si photon diode,
      small volume cylindrical and parallel plate ionization chambers, and radiographic
      films. Tissue maximum ratios (TMR) and total scatter factors (S c.p) were
      measured with the three ionometric (diamond, diode, ion chamber) detectors for 12
      circular beams ranging in diameter from 12.5 to 40 mm. The TMR values obtained
      with the three ionometric detectors agreed well (+/- 1%) for all cone sizes and
      depths investigated when the displacement of the sensitive volume of the detector
      from its front surface is taken into account. The S c.p factors obtained with the
      ionometric detectors also agreed well (+/- 1.2%) for field sizes greater than 20
      mm in diameter. For smaller field sizes, the cylindrical and parallel plate
      chambers measure a smaller S c.p factor, as a result of the steep dose gradients
      across their sensitive volumes. Cross-beam profiles acquired with the diamond
      detector agree well with the measurements with the diode detector and
      radiographic film. A distortion in the measured profiles in terms of broadened
      penumbra is observed with a small volume cylindrical ionization chamber.

PMID- 8746722
TI  - Are database-derived potentials valid for scoring both forward and inverted
      protein folding?
AB  - Database-derived potentials, compiled from frequencies of sequence and structure
      features, are often used for scoring the compatibility of protein sequences and
      conformations. It is often believed that these scores correspond to differences
      in free energy with, in addition, a term containing the partition function of the
      system. Since this function does not depend on the conformation, the potentials
      are considered to be valid for scoring the compatibility of different
      conformations with a given sequence ('forward folding'), but not of sequences
      with a given structure ('inverted folding'). This interpretation is questioned
      here. It is argued that when many body-effects, which dominate frequencies
      compiled from the protein database, are corrected for, the potentials approximate
      a physically meaningful free energy difference from which the partition function
      term cancels out. It is the difference between the free energy of a given
      sequence in a specific conformation and that of the same sequence in a denatured
      like state. Two examples of denatured-like states are discussed. Depending on the
      considered state, the free energy difference reduces to the commonly used scoring
      scheme, or contains additional terms that depend on the sequence. In both cases,
      all the terms can be derived from sequence-structure frequencies in the database.
      Such free energy difference, commonly defined as the folding free energy, is a
      measure of protein stability and can be used for scoring both forward and
      inverted protein folding. The implications for the use of knowledge-based
      potentials in protein structure prediction are described. Finally, the difficulty
      of designing tests that could validate the proposed approach, and the inherent
      limitations of such tests, are discussed.

PMID- 8746723
TI  - Bacterial secretion of the Fab fragment of a mouse monoclonal IgM that reacts
      with IgG variable regions.
AB  - In this report, we describe the expression system that enabled us to produce in
      Escherichia coli the Fab fragment of a mouse IgM that has previously been shown
      to inhibit the binding of IgG to autoantigens by interacting with their variable
      regions. In our system, both light chain and heavy chain fragments were put under
      the control of the malE promoter. The light chain was fused to the MalE signal
      sequence, while the heavy chain variable and first constant region were fused to
      the alkaline phosphatase signal sequence. In this system, after induction of the
      promoter with maltose, the Fab fragment could be detected in a periplasmic
      extract of the bacteria by Western blotting and also by ELISA. This Fab fragment
      was purified on a goat anti-mouse immunoglobulin immunoadsorbent and
      biotinylated. The Fab fragment produced by E.coli reacted with the trinitrophenyl
      (TNP) hapten and F(ab')2 fragments of mouse IgG and these reactivities could be
      specifically inhibited by the corresponding soluble antigens. The dissociation
      constants of this Fab were 1.65 x 10(-6) M for TNP and 5 x 10(-6) M for IgG
      F(ab')2 fragments, indicating that the affinity of the Fab fragment compared with
      that of the whole IgM molecule was similar for TNP but was lower for IgG F(ab')2
      fragments.

PMID- 8746724
TI  - 3-D structure of the D153G mutant of Escherichia coli alkaline phosphatase: an
      enzyme with weaker magnesium binding and increased catalytic activity.
AB  - The substitution of aspartate at position 153 in Escherichia coli alkaline
      phosphatase by glycine results in a mutant enzyme with 5-fold higher catalytic
      activity (kcat) but no change in Km at pH 8.0 in 50 mM Tris-HCl. The increased
      kcat is achieved by a faster release of the phosphate product as a result of the
      lower phosphate affinity. The mutation also affects Mg2+ binding, resulting in an
      enzyme with lower metal affinity. The 3-D X-ray structure of the D153G mutant has
      been refined at 2.5 A to a crystallographic R-factor of 16.2%. An analysis of
      this structure has revealed that the decreased phosphate affinity is caused by an
      apparent increase in flexibility of the guanidinium side chain of Arg166 involved
      in phosphate binding. The mutation of Asp153 to Gly also affects the position of
      the water ligands of Mg2+, and the loop Gln152-Thr155 is shifted by 0.3 A away
      from the active site. The weaker Mg2+ binding of the mutant compared with the
      wild type is caused by an altered coordination sphere in the proximity of the
      Mg2+ ion, and also by the loss of an electrostatic interaction (Mg2+.COO-Asp153)
      in the mutant. Its ligands W454 and W455 and hydroxyl of Thr155, involved in the
      octahedral coordination of the Mg2+ ion, are further apart in the mutant compared
      with the wild type.

PMID- 8746725
TI  - Improved genetic algorithm-based protein structure comparisons: pairwise and
      multiple superpositions.
AB  - Three major improvements to a previously described method for automatic protein
      structure comparison are described. First, a limit to translations for the rigid
      body superposition is now assigned according to the dimensions of the structures
      being compared. Second, examination of the effect of the gap penalty on the
      derivation of a sequence alignment corresponding to a given structure
      superposition has led to a method to evaluate alternative structure-based
      sequence alignments. Third, the pairwise procedure has been generalized to
      multiple structure alignment. This implementation of rigid-body superposition can
      recognize well documented distant relationships which hitherto have required
      consideration of additional features and properties as well as those
      relationships between proteins of different sizes. A much larger common scaffold
      or framework between six globins can be extracted than that obtained using a
      standard algorithm for multiple structure superposition.

PMID- 8746726
TI  - Folding of chains with random and edited sequences: similarities and differences.
AB  - We have investigated the process of protein folding by Monte-Carlo simulation of
      folding occurring in a simple 3D lattice model of a protein globule. We have
      found the range of 'optimal' temperatures where the native fold is achieved by
      the Monte-Carlo process much faster than that by exhaustive sorting of all the
      chain folds. The 'optimal' temperatures are essentially the same for different
      random and 'edited' sequences (for the latter, the native fold energy is
      separated by a considerable gap from the energies of other low-energy folds; for
      random sequences, this gap is negligible). At the 'optimal' temperatures, the
      'edited' chains attain their native fold faster than the random ones. However,
      the essence is that the native folds of 'edited' chains are thermodynamically
      stable at temperatures optimal for fast folding, while the native folds of random
      chains are unstable at the temperatures optimal for fast folding; also, at low
      temperatures where the native folds of random chains are stable, folding kinetics
      is very slow. Consequently, stable native folds are formed slowly by random
      sequences and rapidly by the 'edited' ones.

PMID- 8746727
TI  - Finding the global minimum: a fuzzy end elimination implementation.
AB  - The 'fuzzy end elimination theorem' (FEE) is a mathematically proven theorem that
      identifies rotameric states in proteins which are incompatible with the global
      minimum energy conformation. While implementing the FEE we noticed two different
      aspects that directly affected the final results at convergence. First, the
      identification of a single dead-ending rotameric state can trigger a 'domino
      effect' that initiates the identification of additional rotameric states which
      become dead-ending. A recursive check for dead-ending rotameric states is
      therefore necessary every time a dead-ending rotameric state is identified. It is
      shown that, if the recursive check is omitted, it is possible to miss the
      identification of some dead-ending rotameric states causing a premature
      termination of the elimination process. Second, we examined the effects of
      removing dead-ending rotameric states from further considerations at different
      moments of time. Two different methods of rotameric state removal were examined
      for an order dependence. In one case, each rotamer found to be incompatible with
      the global minimum energy conformation was removed immediately following its
      identification. In the other, dead-ending rotamers were marked for deletion but
      retained during the search, so that they influenced the evaluation of other
      rotameric states. When the search was completed, all marked rotamers were removed
      simultaneously. In addition, to expand further the usefulness of the FEE, a novel
      method is presented that allows for further reduction in the remaining set of
      conformations at the FEE convergence. In this method, called a tree-based search,
      each dead-ending pair of rotamers which does not lead to the direct removal of
      either rotameric state is used to reduce significantly the number of remaining
      conformations. In the future this method can also be expanded to triplet and
      quadruplet sets of rotameric states. We tested our implementation of the FEE by
      exhaustively searching ten protein segments and found that the FEE identified the
      global minimum every time. For each segment, the global minimum was exhaustively
      searched in two different environments: (i) the segments were extracted from the
      protein and exhaustively searched in the absence of the surrounding residues;
      (ii) the segments were exhaustively searched in the presence of the remaining
      residues fixed at crystal structure conformations. We also evaluated the
      performance of the method for accurately predicting side chain conformations. We
      examined the influence of factors such as type and accuracy of backbone template
      used, and the restrictions imposed by the choice of potential function,
      parameterization and rotamer database. Conclusions are drawn on these results and
      future prospects are given.

PMID- 8746728
TI  - Composition analysis of alpha-helices in thermophilic organisms.
AB  - We present a statistical comparison of the amino acid composition in a secondary
      structure element, the alpha-helix, of proteins stable at high temperatures with
      those which are less so. This study has shown that the temperature-dependent Zimm
      Bragg helix propagation value s is not a good predictor for the helix-forming
      tendency of an amino acid in thermostable proteins. However, we have shown that
      delta s, the change in s from 20 to 60 degrees C, accurately predicts the
      direction of the probability shift for 15 amino acids in thermostable protein
      alpha-helices, although it does not predict the magnitude of that change. The
      residues tyrosine, glycine and glutamine show a significant increase in residency
      in alpha-helices for thermostable proteins over their non-thermostable
      counterparts. Significant decreases in alpha-helix residency occur for the
      residues valine, glutamic acid, histidine, cysteine and aspartic acid in proteins
      from thermophilic organisms. Aromatic interactions, hydrogen bonding and a
      reduction of charge may explain the increase observed for tyrosine and glutamine
      and the decrease in glutamic acid and aspartic acid, although packing
      considerations cannot be ruled out. The only physical explanation for the
      increase in glycine would seem to be its positive delta s value.

PMID- 8746729
TI  - Determination of the pKa values of titratable groups of an antigen-antibody
      complex, HyHEL-5-hen egg lysozyme.
AB  - The titration behavior of the ionizable residues of the HyHEL-5-hen egg lysozyme
      complex and its individual components has been studied using continuum
      electrostatic calculations. Several residues of HyHEL-5 had pKa values shifted
      away from model values for isolated residues by more than three pH units. Shifts
      away from the model values were smaller for the residues of hen egg lysozyme. A
      moderate variation in the pKa values of the titratable groups was observed upon
      increase of the ionic strength from 0 to 100 mM, amounting to 1-2 pH units in
      most cases. Under physiological conditions, the net charge of HyHEL-5 was
      opposite that for hen egg lysozyme. Several residues, including those involved in
      the Arg-Glu salt bridges that have been proposed to be important in antibody
      antigen binding, had pKa values that were changed significantly upon binding. The
      main titration event upon antibody-antigen binding appears to be loss of a proton
      from residue GluH50 of the Fv molecule. The limitations of our calculation
      methods and the role they might play in the design of antibodies for use in
      assays, sensors and separations are discussed.

PMID- 8746730
TI  - Molecular modelling of xylose isomerase catalysis: the role of electrostatics and
      charge transfer to metals.
AB  - The two main steps of the mechanism of xylose-xylulose conversion catalysed by D
      xylose isomerase, the ring opening of xylose and the isomerization of the opened
      product by hydride transfer, were investigated by molecular mechanical and
      molecular orbital techniques. The activation energies calculated for these
      reactions clearly showed that hydrogen transfer is the rate-determining step of
      the enzymatic isomerization and that Mg2+ ions activate whereas Zn2+ ions inhibit
      the reaction, in agreement with the experiments. The remarkable differences
      between the net charges of these ions found by molecular orbital calculations and
      the inspection of the protein electrostatic potential around the reaction
      intermediates indicate that the main role of bivalent metal ions should be the
      electrostatic stabilization of the substrate transition states. In order to
      propose a more detailed mechanism, an attempt was made to clarify the effects of
      nearby residues (e.g. His54, Asp57, Lys183, Asp257) in the reaction. Different
      isomerization mechanisms, such as through an enediol intermediate, were examined
      and could be excluded, in addition to the charge-relay mechanism during the ring
      opening.

PMID- 8746731
TI  - Threonine 81 of the trp repressor of Escherichia coli plays an auxiliary role in
      the formation of the corepressor binding pocket.
AB  - A mutational study was performed on the corepressor (L-tryptophan) binding site
      of the trp repressor of Escherichia coli. Threonine 81, one of the residues
      forming the hydrophobic pocket of the binding site, was replaced with Ser, Cys
      and Met by cassette mutagenesis. Biochemical characterization showed that all
      these mutations caused a moderate decrease in tryptophan binding activity (free
      energy change approximately 1 kcal/mol). The results suggested that the binding
      pocket is rather flexible in the vicinity of Thr81. On the other hand, the
      mutations produced a discernible decrease in the repressor activity in vivo,
      apparently by weakening or eliminating the hydrogen bond between Thr81 and the
      operator DNA, as well as by introducing possible side-chain rearrangement.

PMID- 8746732
TI  - Contribution of a disulfide bridge to the stability of 1,3-1,4-beta-D-glucan 4
      glucanohydrolase from Bacillus licheniformis.
AB  - Bacillus 1,3-1,4-beta-glucanases possess a highly conserved disulfide bridge
      connecting a beta-strand with a solvent-exposed loop lying on top of the extended
      binding site cleft. The contribution of the disulfide bond and of both individual
      cysteines (Cys61 and Cys90) in the Bacillus licheniformis enzyme to stability and
      activity has been evaluated by protein engineering methods. Reduction of the
      disulfide bond has no effect on kinetic parameters, has only a minor effect on
      the activity-temperature profile at high temperatures, and destabilizes the
      protein by less than 0.7 kcal/mol as measured by equilibrium urea denaturation at
      37 degrees C. Replacing either of the Cys residues with Ala destabilizes the
      protein and lowers the specific activity. C90A retains 70% of wild-type (wt)
      activity (in terms of Vmax), whereas C61A and the double mutant C61A-C90A have
      10% of wt Vmax. A larger change in free energy of unfolding is seen by
      equilibrium urea denaturation for the C61A mutation (loop residue, 3.2 kcal/mol
      relative to reduced wt) as compared with the C90A mutation (beta-strand residue,
      1.8 kcal/mol relative to reduced wt), while the double mutant C61A-C90A is
      approximately 0.8 kcal/mol less stable than the single C61A mutant. The effects
      on stability are interpreted as a result of the change in hydrophobic packing
      that occurs upon removal of the sulfur atoms in the Cys to Ala mutations.

PMID- 8746733
TI  - Follow-up studies of a representative sample of children with severe mental
      handicap in Poland.
AB  - A representative sample of 260 Polish children, aged 5-14 years, identified
      between 1964 and 1965 in an epidemiological study as severely mentally
      handicapped (IQs ranging from 0 to 51) were followed up twice: (I) after 10 years
      (in 1975-1976); and (II) after 23 years (in 1987-1988). At both follow-ups, all
      surviving subjects were contacted, and psychological and sociological data were
      gathered; the findings presented here pertain mostly to follow-up II. The great
      majority of subjects (85%) lived with their families, and the remainder resided
      in an institution. Only 10% of subjects (living with one exception in families)
      currently had a higher level of intellectual functioning than that of severe
      mental handicap. Among this group were individuals of relatively better health,
      without speech disorders, who had attended schools, had some vocational training,
      had been or were employed, and had families of their own, i.e. were self
      dependent with a life-style similar to that of other people of their age and
      social background. Of the remainder, about 40% retained the same relative level
      of intellectual and social functioning, and about 50% deteriorated, particularly
      those in institutions. This latter group has remained in the role of permanent
      children, depending on others for care and maintenance.

PMID- 8746734
TI  - Experienced and inexperienced health care workers' beliefs about challenging
      behaviours.
AB  - Within a behavioural framework, staff responses to challenging behaviours have
      been identified as likely to ensure the long-term maintenance of such behaviour.
      However, little has been done to understand why staff behave as they do. The
      present paper hypothesized that staff's beliefs about the causes of challenging
      behaviours may be an important factor in determining staff responses to it.
      Beliefs about causes of three topographies of challenging behaviour (self-injury,
      stereotypy and aggression) were elicited from 148 experienced and 98
      inexperienced institutional staff and nursing students using a questionnaire
      measure. Results showed that experienced participants held beliefs that were more
      consistent with contemporary theories of challenging behaviours than
      inexperienced participants. Experienced participants also distinguished between
      the behaviours in terms of their causes. These data were interpreted as
      reflecting a 'needs-based' rather than a 'functional' approach to intervention
      for challenging behaviours. Implications for staff training, community living and
      future research on staff behaviour were briefly considered.

PMID- 8746735
TI  - The effects of deinstitutionalization on adults with learning disabilities.
AB  - We compared a group of people with learning disabilities who have been
      deinstitutionalized with a control group remaining in an institution on measures
      of adaptive and maladaptive behaviour, community living skills, social skills,
      and quality of life. In general, there was no change over 30 months for the
      control group. Changes for the experimental group were either not seen or were
      generally modest in scale, and tended to occur within 6 months of moving, the
      measures staying relatively stable thereafter. Implications for detailed
      examination of the effects of deinstitutionalization were discussed.

PMID- 8746736
TI  - The prescribing of neuroleptic drugs for people with learning disabilities living
      in Leicestershire.
AB  - Neuroleptics are prescribed for 23% of individuals with learning disabilities
      resident in Leicestershire, England. The rate of neuroleptic prescription is
      significantly higher in individuals resident in N.H.S. facilities (44%) than in
      non-N.H.S. managed community facilities (13%). Significantly higher doses of
      neuroleptics are prescribed to individuals resident in N.H.S. facilities.
      However, ratings for the level of behavioural disturbance were significantly
      higher in N.H.S. facilities. The decision to prescribe neuroleptics was
      associated with disturbed behaviour, and higher doses of neuroleptic medication
      prescribed were associated with more disturbed behaviour.

PMID- 8746737
TI  - Offending by adults with learning disabilities and the attitudes of staff to
      offending behaviour: implications for service development.
AB  - The aims of this study were: (I) to identify all adults with learning
      disabilities living in residential homes or attending day services in the
      Cambridge Health District in contact with the criminal justice system during
      1992; (2) to evaluate the responses of services involved; and (3) to investigate
      the attitudes of staff and the policies of the services to 'offending behaviour'.
      Details of offences committed and the response of the police, health and social
      services, and other agencies were obtained by direct interview with the senior
      staff and through examination of case records. The attitudes of staff to
      offending behaviour was investigated by the use of a semi-structured
      questionnaire. Seven (2%) out of 358 adults with learning disabilities were
      reported to have had contact with the police during 1992. The eight offences
      allegedly committed by the seven people were two acquisitive offences, two sexual
      offences, one assault, one wasting of police time, one offence against the Public
      Order Act and one traffic offence. One offender was cautioned after the Crown
      Prosecution Service discontinued the case because of lack of evidence, while the
      other alleged offenders received informal warnings. None of the seven alleged
      offenders were prosecuted. Three alleged offenders lived in hostel accommodation,
      yet hostel accommodation only accounts for 7.8% of adults with learning
      disabilities living in the Cambridge Health District. Because of a lack of
      operational policies on offending behaviour, there were no existing referral
      structures for people who might need specialist health service support. Referrals
      tended to be inconsistent, with a considerable time-lag between offence and
      referral. Tolerance levels towards offending behaviour were extremely high in the
      two hostels, 20 group homes and day centres which were included in this study.
      Theft and criminal damage was hardly ever reported. Thirty establishments were
      visited during the course of this study. Of these establishments, staff in 12
      said they would always report a major assault. In only three would a sexual
      assault or indecent exposure always be reported if it was to occur. Staff at one
      residential establishment said they would hesitate to report rape and the staff
      in another two would consider the circumstances before reporting it to the
      police.

PMID- 8746738
TI  - Rapid cycling bipolar affective disorder and familial learning disability
      associated with temporal lobe (occipitotemporal gyrus) cortical dysplasia.
AB  - This case report describes a hitherto unreported association between temporal
      cortical dysplasia and rapid cycling bipolar affective disorder in a learning
      disabled young man with a family history of rapid cycling bipolar affective
      disorder in two dysmorphic and learning disabled maternal uncles, and probably
      learning disability in the mother and grandmother. An identical family with
      similar findings could not be located in the English literature.

PMID- 8746739
TI  - The use of a low phenylalanine diet in response to the challenging behaviour of a
      man with untreated phenylketonuria and profound learning disabilities.
AB  - If phenylketonuria (PKU) is not treated from an early age with a reduced
      phenylalanine diet, irreversible brain damage may occur. Although dietary
      intervention can do nothing to alter this impairment once it occurs, there is
      some evidence to suggest that a low phenylalanine diet may help to reduce the
      level of behavioural disturbances frequently experienced by people with untreated
      PKU. Using this evidence, dietary intervention was used in response to the
      challenging behaviour of a 30-year-old man with profound learning disabilities.
      Initial improvements were observed, but overall the results were inconclusive.
      Possible confounding factors are discussed. An unusual reaction to neuroleptic
      medication whilst on the diet is also documented.

PMID- 8746740
TI  - Age-specific standardized mortality rates in people with learning disability.
AB  - The aim of the present study was to calculate the age-and sex-specific
      standardized mortality ratios (SMRs) in two populations of people with learning
      disability (LD). These populations included people living in institutions and
      community settings. It was found that SMRs tended to be raised for both males and
      females in each population, but SMRs do not always significantly differ from
      unity. For the combined Register populations, SMRs are generally significantly
      greater than unity. We conclude that these data provide evidence that death rates
      for people with LD are often higher than in the general population.

PMID- 8746741
TI  - Short-term memory in persons with intellectual disabilities and Down's syndrome.
AB  - The present study was designed to investigate verbal and spatial short-term
      memory abilities in persons with Down's syndrome (DS) and intellectual disability
      (ID) of different aetiology. For this purpose, we compared performances of DS (n
      = 15; mean mental age = 5.2 years; SD = 1.2 years; mean chronological age = 16.6
      years; SD = 2.9 years) and ID subjects (n = 14; mean mental age = 5.8 years; SD =
      2.1 years; mean chronological age = 16.4 years; SD = 2.5 years) with those of
      normally developed subjects matched for mental age (n = 24) on tasks of forward
      and backward immediate recall of verbal and spatial sequences. Our results are
      discussed in the light of the Working Memory model developed by Baddeley (1986,
      1990). Altogether, our data documents a deficit of verbal and spatial backward
      spans in persons with DS. The deficit seems to be specific for this particular
      aetiology group, confirming the hypothesis that ID is not a uniform condition,
      characterized by an undifferentiated delay of the cognitive development, but
      rather that it is characterized by a deficit in a complex cognitive system in
      which some cognitive abilities can be disrupted more than others (Detterman 1987;
      Vicari et al. 1992).

PMID- 8746742
TI  - Obstetric factors in Asperger syndrome: comparison with high-functioning autism.
AB  - Asperger syndrome (AS) is a pervasive developmental disorder widely regarded as a
      mild variant of autism. To investigate if AS is associated with a history of
      fewer obstetric insults compared to autism, we examined the developmental history
      and obstetric records of 10 males with AS (mean full scale IQ 95.3), and compared
      them with 10 autistic males with a full scale IQ of 70 or above (so-called high
      functioning autism; mean full scale IQ 82.6). Males with AS showed a trend toward
      lower Apgar scores at one minute (chi-square = 4; df = 1; P = 0.04) and were more
      likely to have been born to mothers outside the optimal age group of 20-30 years
      (chi-square = 5; df = 1; P = 0.02). They were also less likely to have been
      irritable and floppy as infants (chi-square = 3.8; df = 1; P = 0.05). However,
      the total optimality scores did not differ significantly between the two groups.

PMID- 8746743
TI  - Molecular genetic analysis of mentally retarded males with features of the
      fragile-X syndrome.
AB  - The fragile-X[fra(X)] or Martin-Bell syndrome is the most common familial cause
      of mental retardation and is characterized by the presence of an Xq27.3
      chromosome fragile site. Unstable DNA sequences representing large increases in
      the number of CGG trinucleotide DNA base repeats of the FMR-1 gene are located at
      the fragile site and responsible for the fra(X) syndrome. In order to identify
      whether cytogenetically normal yet mentally retarded males without a known cause
      of their retardation had expansion of the CGG repeat segment of the FMR-I gene,
      molecular genetic studies using Southern hybridization were performed with two
      DNA probes (fxa241 and Ox1.9) following digestion of genomic DNA from each
      patient with restriction enzymes Pstl and EcoRl/Eagl, respectively. DNA studies
      were performed on 20 (12.3%) out of 162 (122 white and 40 black people)
      cytogenetically normal mentally retarded males without a known cause of their
      retardation, but with high anthropometric discriminant values and/or clinical
      checklist scores identified previously and consistent with the fra(X) syndrome.
      None of the 20 males showed expansion of the CGG repeat of the FMR-1 gene
      detectable with the two probes used in this study. While heterogeneous single
      base pair substitutions, or small deletions or insertions in the FMR-I gene could
      exist in our patients, aberrations in other X-linked mental retardation genes,
      not identified to date but whose gene product can produce a phenotype similar to
      fra(X), either independently or in conjunction with the recently identified FMR-I
      protein, should be considered and are under investigation. Our study supports the
      idea that major FMR-I gene expansion detectable with Southern hybridization is
      rare in cytogenetically normal mentally retarded males, including those with
      physical and behavioural features seen in the fra(X) syndrome.

PMID- 8746744
TI  - Diurnal variations in vision and relations to circadian melatonin secretion in
      multiple sclerosis.
AB  - It has long been recognized that symptoms of multiple sclerosis (MS) wax and wane
      with fluctuations occurring on an hour to-hour basis throughout a 24 hour period.
      It has been proposed that changes in circadian core body temperature, which alter
      axonal conductivity, may account for the fluctuations of symptoms in MS. A 51
      year-old man with MS is reported in whom visual acuity deteriorated throughout
      the course of the day only to improve again at night between 10:00 p.m. and 2:00
      a.m. These changes in vision were unrelated to rest or physical activity, but
      appeared to coincide with the circadian secretion of melatonin which is coupled
      to the circadian temperature rhythms. Since melatonin lowers body temperature, it
      is hypothesized that the nocturnal rise in melatonin secretion was related to
      improvement in vision in this patient. This hypothesis is supported by the
      observation that administration of melatonin (3 mg, orally) at 2:00 p.m., when
      the patient experienced severe blurring of vision, resulted within 15 minutes in
      a dramatic improvement in visual acuity and in normalization of the visual evoked
      potential latency after stimulation of the left eye. Moreover, since the pineal
      gland is a thermoregulatory organ which functions to prevent excessive rise of
      body temperature, it is possible that since MS is associated with dysfunction of
      the pineal gland, these patients may experience diminished capacity to eliminate
      heat at rest or during physical activity with resultant elevation of body
      temperatures which may further compromise neurologic functions by causing failure
      of axonal conduction.

PMID- 8746745
TI  - Study of behavior of rats with gluten-induced enteropathy.
AB  - Association of different psychological and neurological disturbances with gluten
      intake in coeliac patients was repeatedly described. In the present study gluten
      induced enteropathy was elicited in rats by prolonged intragastric administration
      of gliadin from birth to 10 weeks. Various neurological (contact and visual
      placing reactions, equilibrium on horizontal bar) and behavioral tests (open
      field and Morris water maze task) were used to assess the possible deficits. No
      substantial differences were found in the behavior of rats fed with gliadin
      compared with those fed with bovine serum albumin (control group). The only
      difference found between control and experimental rats was that gliadin-fed rats
      showed slightly higher emotionality in the open field test. It is concluded that
      prolonged application of gliadin to young rats at enteropathy-inducing dosages
      does not modify their behavior.

PMID- 8746746
TI  - The effects of generalized seizure activity on the cerebellar auditory potential.
AB  - The effects of generalized seizure activity (GSA) on the primary cortical
      component of the cerebellar auditory evoked potential [CERAEP] were studied in
      the awake rat. GSA was induced by electroconvulsive shock (ECS) [80 mA for 600
      ms]. CERAEPs proved largely resistant to GSA, even during the ictal period. Any
      minor alterations to the waveform were very transient and normal morphology was
      restored within 1-2 min after ECS. Overall, there was a mean decrease in
      amplitude of 2.6 microV associated with an increase in latency of 0.2 ms. These
      findings are consistent with those of GSA on the fast and slow components of the
      brainstem auditory evoked potential and imply that activity generated in the more
      caudal parts of the central auditory system is largely invulnerable to GSA. In
      contrast, a later component of the CERAEP waveform of uncertain origin was
      totally abolished by the action of ECS.

PMID- 8746747
TI  - FO-dependence, number alteration, and non-systematic behaviour of the formants in
      German vowels.
AB  - In acoustic theory, formant pattern differences within one vowel identify are
      related to differences in the speaker groups or in the types of vocalization.
      Yet, studies of vowel synthesis indicate that formant patterns can also vary
      strongly in relation either to pitch or to formant number alterations. Within
      this study, natural vocalizations of nine German vowels were investigated with
      regard to different formant patterns representing the same vowel identity, apart
      from differences in speaker groups and vocalization types. The results show i) FO
      dependence of the lower formants < 1.5-2 kHz; ii) occurrence of natural one
      formant back and two-formant front vowels; iii) a non-systematic relationship
      between FO and the formants, and a non-systematic relationship between formant
      patterns of different formant numbers. The implications for psychophysics,
      physiology and perception of speech are discussed.

PMID- 8746748
TI  - Long term beneficial effects of weak electromagnetic fields in multiple
      sclerosis.
AB  - A 39 year-old severely disabled woman with a 19 year history of chronic relapsing
      remitting multiple sclerosis (MS) began to experience improvement in symptoms
      within 24 hours after she received experimental treatment with picotesla
      electromagnetic fields (EMFs). Pattern reversal visual evoked potential (VEP)
      study obtained three weeks after the initiation of the first magnetic treatment
      showed a return to normal of the P100 latencies in each eye. The patient
      continued to receive 1-2 EMFs treatments per week and during the following 32
      months she made a dramatic recovery with resolution of diplopia, blurring of
      vision, dysarthria, ataxia of gait, and bladder dysfunction as well as
      improvement in fatigue, heat tolerance, mood, sleep, libido, and cognitive
      functions. VEP studies, which were repeated in April of 1995 more than 2 1/2
      years after the initiation of magnetic treatment, showed that P100 latencies
      remained normal in each eye providing objective documentation that continued
      application of these EMFs may sustain normal conduction in the damaged optic
      pathways over a long period of time. This is the first case report documenting
      the dramatic long term beneficial effects of treatment with picotesla range EMFs
      in a patient with MS.

PMID- 8746749
TI  - Regional cerebral blood flow and neuropsychological performance in a Danish
      family with X-linked bulbo-spinal neuronopathy.
AB  - Regional Cerebral Blood Flow (rCBF) measurements and neuropsychological
      evaluation were performed in 6 patients from a Danish family affected with X
      linked Bulbo-Spinal Neuronopathy (XBSN). This inherited form of motor neuron
      disease (MND) has been shown to affect various functions within the nervous and
      the endocrine systems. We investigated the possibility that focal or diffuse
      cortical deficits, already demonstrated in MND, were present in XBSN. The global
      CBF values of the patients, when compared to age- and sex-matched healthy
      controls, were found reduced, but no focal rCBF alterations, nor increased
      regional side-to-side asymmetry were observed. The neuropsychological evaluation
      showed no cognitive impairments. We conclude that cortical perfusion and
      cognitive functions are not significantly altered in XBSN.

PMID- 8746750
TI  - Reversal of alexia in multiple sclerosis by weak electromagnetic fields.
AB  - The occurrence of cognitive deficits in patients with multiple sclerosis (MS) has
      been recognized since 1877 when Charcot first observed "enfeeblement of memory"
      in his patients. Cognitive deficits have been reported in almost 50% of patients
      with a relapsing-remitting course and in a significantly higher percentage of
      patients with a chronic progressive course leading to intellectual disability
      which is often severe enough to preclude employment. MS is considered a form of
      subcortical dementia and the occurrence of classical cortical disorders such as
      aphasia, agnosia and apraxia is reported to be rare in the disease. However, in
      my experience alexia, a reading impairment unrelated to visual acuity or visual
      field defects, is common in patients with MS. Recently, I reported that treatment
      with picotesla range electromagnetic fields (EMFs) is an efficacious modality in
      the management of both the motor and cognitive symptoms of MS. Three patients
      with MS who developed alexia as a manifestation of the disease are presented. In
      all patients the alexia was reversed several months after they began treatment
      with EMFs. Since alexia usually reflects a disconnection syndrome whereby lesions
      involving the left visual cortex and the splenium of the corpus callosum
      disconnect language association areas from visual association areas, it is
      suggested that reversal of the alexia in these patients by EMFs was related to
      improved interhemispheric transcallosal transmission of visual information. In
      addition, it is conceivable that changes in the metabolism of monoamines, which
      are involved in visual information processing and reading comprehension, may have
      been important in causing reversal of the alexia. This report further supports
      the unique efficacy of this treatment modality in reversing specific cognitive
      deficits in MS.

PMID- 8746751
TI  - Resolution of dysarthria in multiple sclerosis by treatment with weak
      electromagnetic fields.
AB  - It has been reported that 50% or more of patients diagnosed with multiple
      sclerosis (MS) exhibit speech impairment (dysarthria) which in some cases can be
      exceedingly disabling. Currently there is no effective medical treatment for the
      dysarthria of MS which occurs as a result of lesions to the cerebellum and its
      outflow tracts. It was reported recently that extracranial application of brief
      AC pulsed electromagnetic fields (EMFs) in the picotesla (pT) range intensity
      produced in patients with MS sustained improvement in motor functions including
      cerebellar symptomatology. This communication concerns two MS patients with a
      chronic progressive course who exhibited severe dysarthria which improved already
      during the initial treatment with pulsed EMFs and which resolved completely 3-4
      weeks later. Since application of EMFs has been shown to alter: (a) the resting
      membrane potential and synaptic neurotransmitter release through an effect
      involving changes in transmembrane calcium flux; and (b) the secretion of pineal
      melatonin which in turn influences the synthesis and release of serotonin (5-HT)
      and gamma-amino butyric acid (GABA) in the cerebellum, it is suggested that the
      immediate improvement of the dysarthria occurred as a result of changes in
      cerebellar neurotransmitter functions particularly 5-HT and GABA rather than from
      remyelination.

PMID- 8746752
TI  - ERP spectral analysis of cholesterol rich patients.
AB  - Visual event-related potentials (ERPs) were studied in twenty
      hypercholesterolemic (HC) patients and twenty age-matched healthy controls. ERPs
      were recorded in two different experimental conditions that the target stimulus
      (red light) was counted (Test 1) or uncounted (Test 2). Amplitude spectra of ERPs
      were computed by transient response-frequency characteristics (TRFC) method.
      Their maxima were found to occupy the frequency bands of 1-2, 3-4, 5-7, 8-12, 13
      20, 20.5-32 Hz. The amplitude mean (decibel) of 1-2 and 3-4 frequency bands were
      decreased in Test 2 compared to Test 1 in the control group, but no significant
      amplitude differences were found between Test 1 and Test 2 in the HC group.

PMID- 8746753
TI  - Event-related potentials in hypertriglyceridemia.
AB  - Event-related potentials (ERPs) of twenty-three hypertriglyceridemic (HTG)
      patients and twenty-three age-matched healthy controls were recorded in two
      different experimental conditions that the target stimulus was counted (Test 1)
      or uncounted (Test 2). Latencies of each wave were inside normal limits in all
      patients. No differences were found in the P3b amplitudes of Test 1 case among
      HTG and control subjects. Amplitude spectra of ERPs were computed by transient
      response-frequency characteristics (TRFC) method. Their maxima were found to
      occupy the frequency bands of 1-2, 3-4, 5-7, 8-12, 13-20, 20.5-32 Hz. When
      comparing Test 1 with Test 2, significant amplitude differences were found in 1-2
      and 3-4 frequency bands of controls and 1-2 and 13-20 frequency bands of patient
      group.

PMID- 8746754
TI  - A testable model of global cortical organization.
AB  - This report advances a testable model of cortical organization which is tied to
      gamma band (20-150 Hz) neuroelectric oscillations. The elements of the model
      function as pattern recognizers and are assumed to be composed of a few cm2 of
      cortical tissue. Presumed modes of instability in the activity of this network of
      large units are proposed as the underlying neurophysiological basis of a variety
      of psychopathologies. The model is used to predict macroscopic neuroelectric
      measureables which will be present in patients who display these
      psychopathologies. Two techniques are described for identifying gamma band
      oscillations in neurophysiological recordings.

PMID- 8746755
TI  - Neuropsychological characteristics of learning disabled/gifted children.
AB  - The neuropsychological characteristics of 68 learning-disabled/gifted children
      (LD/Gifted) were studied using the Halstead-Reitan Neuropsychological Test
      Battery for Children (HRNB-C). The proportion of LD/Gifted children identified as
      impaired was low compared to previous research that has examined the proportion
      of school-identified learning-disabled students who scored within the impaired
      range on the HRNB-C. Consistent with previous research, the results of this study
      indicated that LD/Gifted children were also more likely to demonstrate impairment
      on the Tactual Performance Test-Memory, Tactual Performance Test-Localization,
      and Trails B-Errors components of the HRNB-C.

PMID- 8746756
TI  - Factor analysis of the Halstead-Reitan Neuropsychological Test Battery for Older
      Children.
AB  - Studies of the factor structure of the Halstead-Reitan Neuropsychological Test
      Battery for Older Children (HRNB-C) have reported solutions ranging from 5 to 7
      constructs. The current study examined the underlying factor structure of the
      HRNB-C using only tests from the Battery itself with 800 learning disabled
      children. The results showed a four factor solution to be the most heuristic.
      These dimensions were identified as Speed of Operation, Tactile-Motor
      Integration, Attention, and Visuo-Spatial Memory. When ancillary tests are
      excluded it is argued that four factors provide the best description of the
      underlying structure of the HRNB-C.

PMID- 8746757
TI  - The effect of aging on spectral parameters of event-related potentials.
AB  - Forty-two healthy subjects ranging in age from 20 to 73 were divided into three
      groups according to age; a young group (20-33 years), a middle-aged group (34-49
      years) and older group (50-73 years). Event-related potentials (ERPs) of three
      groups were recorded in two different experimental conditions that the infrequent
      stimulus was counted (Test 1) or uncounted (Test 2). ERPs were elicited using
      infrequent and frequent stimuli as red and green lights respectively. Spectral
      analysis of ERPs showed that decibel (dB) values of 1-2 and 3-4 Hz in young and
      middle-aged groups while dB value of 1-2 Hz in older group were significantly
      decreased in Test 2 compared with Test 1. When the number of subjects displaying
      amplitude maximum in each frequency band was considered, significant differences
      were found in 1-2 and 5-7 Hz frequency bands of young and middle-aged groups, but
      no significant differences were found for older group.

PMID- 8746759
TI  - The problems with exocytosis.

PMID- 8746758
TI  - A unifying hypothesis for acetylcholine release.
AB  - Mediatophore is the only nerve terminal membrane protein known to translocate
      acetylcholine upon calcium action. It is localized at the active zone. In this
      review we attempted to describe its role in relation to the vesicular and
      membrane protein complexes that are formed at the active zone. The model pictures
      a possible set of sequential steps that lead to exocytosis. The smallest quantal
      events are attributed to mediatophore opening momentarily, while synaptic
      vesicles synchronize release by controlling the calcium microdomain. A clear
      distinction is made between sub-quantal ACh release preserved after Botulinum
      toxin action, and exocytosis of vesicular contents. A cybernetic model for
      release and exocytosis related to protein interactions is presented for future
      works.

PMID- 8746760
TI  - The membrane fusion machine and neurotransmitter release.

PMID- 8746761
TI  - The chemical neuroanatomy of the mammalian pineal gland: neuropeptides.
AB  - The mammalian pineal gland contains multiple afferent peptidergic nerve fibres.
      Sympathetic nerve fibres, with their origin in the superior cervical ganglia,
      contain neuropeptide Y colocalized with norepinephrine. Other pinealopetal nerve
      fibres, probably originating in the pterygopalatine ganglion, contain vasoactive
      intestinal peptide and peptide histidine isoleucine. Fibres containing substance
      P and calcitonin gene-related peptide have also been demonstrated in pinealopetal
      nerve fibres. These fibres might originate in the trigeminal ganglion. The
      neurotransmitter content of the fibres of the central innervation, innervating
      the gland from the brain via the pineal stalk, has not been elucidated. However,
      strong indications for the presence of neuropeptide Y, substance P, somatostatin,
      and vasopressin in these fibres have been presented. Recent immunohistochemical
      studies have further shown the presence of subtypes of pinealocytes containing
      neuropeptides. Thus, pinealocytes containing beta-endorphin, leu-enkephalin, and
      somatostatin have been demonstrated in the gland. Immunohistochemistry at the
      electron microscopical level has shown, that in some species, leu-enkephalin
      containing pinealocytes make synaptic contacts with other pinealocytes indicating
      of paracrine regulation of the pineal gland. It must however be emphasized that
      large interspecies variations exist with regard to the peptidergic pineal
      innervation and its content of peptidergic cells.

PMID- 8746762
TI  - Preferential stimulation of glutamate release by 4-aminopyridine in rat striatum
      in vivo.
AB  - The potassium channel blocker 4-aminopyridine (4-AP) is a potent convulsant drug
      which, in vitro, stimulates the release of neurotransmitter amino acids. We have
      studied the effect of 4-AP in vivo on the extracellular concentration of amino
      acids in rat striatum, by means of microdialysis and HPLC. Perfusion with 4-AP in
      the awake animal produced intense motor alterations, including barrel turning and
      running fits. Therefore, most microdialysis experiments were carried out in
      anesthetized rats. Perfusion with 20-75 mM 4-AP for 12.5 min resulted in a
      massive increase in extracellular glutamate (up to 20-fold), smaller increases in
      aspartate and taurine (up to 10-fold) and slight increments in glutamine,
      alanine, glycine and GABA. In contrast, perfusion with 100 mM K+ produced,
      mainly, an increment in taurine (7-fold) and modest increases in glutamate and
      aspartate (100-300%), as well as a notable decrease in glutamine.
      Tetraethylammonium (TEA, 120 mM) perfusion induced taurine and glutamate
      elevations similar to those after high K+, but glutamine was not affected. In
      unanesthetized rats, perfusion with 40 mM 4-AP induced changes in extracellular
      amino acids similar to those observed under anesthesia. In these animals neither
      high K+ nor TEA affected significantly the motor behavior. The results suggest
      that an enhancement of glutamatergic synaptic transmission, rather than a general
      depolarizing action, is an important factor in the neuronal hyperexcitability
      induced by 4-AP, which is consistent with the previously demonstrated inhibition
      of its convulsant effect by glutamate receptor antagonists.

PMID- 8746763
TI  - Acute MPTP treatment produces no changes in mitochondrial complex activities and
      indices of oxidative damage in the common marmoset ex vivo one week after
      exposure to the toxin.
AB  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to cause a
      Parkinsonian syndrome in man and non-human primates. Hypotheses concerning the
      pathogenetic mechanisms of MPTP toxicity on nigro-striatal dopaminergic neurons
      relate to impairment of mitochondrial function and oxidative stress. However,
      surprisingly few primate studies addressed these issues ex vivo. Thus, the
      present study assessed the enzyme activities of the respiratory chain, GSH/GSSG
      and ubiquinol/ubiquinone content in the MPTP primate model (common marmoset,
      Callithrix jacchus; 2 mg MPTP-hydrochloride/kg body wt were injected
      subcutaneously (s.c.) on four consecutive days; animals were sacrificed 7 days
      after last MPTP exposure). Activities of respiratory chain enzymes were measured
      in crude homogenates of the caudate nucleus, because the probable toxic
      metabolite of MPTP, MPP+, is transported into dopaminergic neurons via the
      dopamine uptake system in striatal synapses and mitochondria are concentrated in
      axonal terminals. Since MPP+ can damage membranes of axonal terminals of nigro
      striatal neurons we measured GSH/GSSG contents in the putamen and
      ubiquinol/ubiquinone concentrations in the substantia nigra and putamen as
      indices of oxidative damage. At the time of sacrifice MPTP-induced deficits
      comprised severe behavioural Parkinsonian symptoms, profound depletion of
      striatal dopamine and its major metabolites as well as pronounced loss of nigro
      striatal neurons. Despite these severe lesions, acute MPTP treatment had no
      effect on any of the enzymes of the respiratory chain in the caudate nucleus and
      indices of oxidative damage in both the substantia nigra and putamen. These
      results suggest that factors other than mitochondrial impairment and/or oxidative
      stress may be involved in MPTP neurotoxicity in primates. Alternatively, early
      compensatory mechanisms and/or transient effects could account for the reported
      results and will be discussed.

PMID- 8746764
TI  - Lack of long-term changes in cocaine and monoamine concentrations in rat CNS
      following chronic administration of cocaine.
AB  - In previous studies, we reported time-dependent and dose-dependent changes in the
      rat dopaminergic receptor system following chronic administration of cocaine. The
      aim of the present investigation was to monitor the concentration of monoamines
      (using HPLC-ECD) and cocaine (using GC-PCI/MS) in rat CNS following a dose
      schedule of 5, 10, 15, 20 and 25 mg/kg, i.p., b.i.d. for 21 days. 12 h after the
      last cocaine injection, cortical and striatal concentrations of monoamines and
      their metabolites were not significantly different in saline vs cocaine treated
      animals. In addition, the cocaine concentration in the brain regions examined did
      not change with the different doses used. Accumulation of a metabolite of cocaine
      (ecgonine methyl ester) was the only alteration found. These results indicate
      that alterations in the dopaminergic receptor system following chronic cocaine
      administration are not due to changes in neurotransmitter concentration or
      accumulation of cocaine in the brain.

PMID- 8746765
TI  - Protein phosphorylation in the blood-brain barrier. Possible presence of MARCKS
      in brain microvessels.
AB  - The protein phosphorylation in rat brain microvessels has been examined; the
      major phosphorylated proteins correspond to a doublet of molecular weight 134-141
      kDa, and four proteins of approx. 25, 55, 80 and 200 kDa. TPA (12-O
      tetradecanoylphorbol-13-acetate) enhanced, in a few minutes, the phosphorylation
      of three major protein substrates with apparent molecular weights of 17.5, 44.5
      and 80 kDa. These effects are inhibited by staurosporine. The 80 kDa protein
      resulted to be myristoylated alanine-rich C kinase substrate (MARCKS). This work
      demonstrates that protein kinase C plays an important role in protein
      phosphorylation in blood-brain barrier (BBB).

PMID- 8746766
TI  - Voltage-sensitive Ca2+ channels in rat striatal synaptosomes: role on the [Ca2+]i
      responses to membrane depolarization.
AB  - The fluorescent Ca2+ indicator Indo-1 was used to study the effect of
      depolarization evoked by KCl or 4-aminopyridine (4-AP) on the intracellular free
      calcium concentration responses (delta[Ca2+]i) in rat striatal synaptosomes.
      Depolarization of the synaptosomes with [KCl] > 7.5 mM induced a rapid increase
      of the [Ca2+]i followed by a decay towards a plateau. The size of the [Ca2+]i
      response varied sigmoidally with the synaptosomal membrane potential, with a
      transition potential of -27.3 mV. Depolarization with 4-AP evoked a dose
      dependent sustained increase of the [Ca2+]i. Nitrendipine, omega-Conotoxin GVIA
      (omega-CgTx) and omega-Agatoxin IVA (omega-Aga IVA) were used to evaluate the
      relative role of L-, N-, P- and possibly Q-type voltage-sensitive Ca2+ channels
      (VSCCs) on the [Ca2+]i changes evoked by each of the two depolarizing agents.
      Nitrendipine caused only about 10% inhibition of the effect of either agent on
      the [Ca2+]i, suggesting that the L-type VSCCs have a modest contribution. The
      omega-CgTx decreased the response to KCl and 4-AP by 15 and 30%, respectively,
      but the latter effect may be partially due to a non-specific effect on Na+
      channels. The omega-Aga IVA reduced the response to 4-AP by 26.5%, and this
      effect was additive to that of omega-CgTx, further suggesting that the striatal
      nerve terminals possess P- and/or Q-type, in addition to N-type Ca2+ channels.
      Neomycin (0.35 mM), tentatively used as an antagonist of the P-type channels, had
      a potent effect, decreasing the response to K(+)-depolarization and to 4-AP by,
      respectively, 32.5 and 48.5%. It is suggested that at the concentration used the
      antibiotic also partially blocks VSCCs which do not belong to the L-, N-, P- or Q
      type VSCCs. We conclude that striatal nerve endings are equipped with at least
      four to five pharmacologically distinct classes of VSCCs, which are sensitive to
      well known antagonists of the L-, N-, P-, and Q-type VSCCs.

PMID- 8746767
TI  - Key histidine residues in the nicotinic acetylcholine receptor.
AB  - Reactivity of histidine residues of the Discopyge tschudii nicotinic
      acetylcholine receptor was studied by reaction with DEP and the influence of
      their modification on functional properties of the receptor was evaluated.
      Determination of two kinetically distinguishable classes was achieved. The fast
      reacting class is composed of 7 histidine residues with an apparent velocity
      constant k1 = 0.0248 +/- 0.0031 min-1. The second includes--at least--21
      histidine residues with a velocity constant k2 = 0.0016 +/- 0.0009 min-1. The
      circular dichroism spectra of the native receptor and the most DEP-derivative
      indicate no significant modifications in the alpha-helix content, and fourth
      derivative spectroscopy analyses show that the environment around the aromatic
      amino acids remains unchanged. DEP treatment of the receptor results in a time-
      and reagent concentration-dependent loss of its alpha-bungarotoxin binding
      ability; these results agree with those obtained with the membrane-bound
      receptor. The decrease in the neurotoxin binding capacity was correlated with the
      DEP-reaction extent of the slow groups. Incorporation of 1.93 +/- 0.23 mol of DEP
      accounted for the maximal binding capacity drop, thus indicating the involvement
      of two histidine residues per alpha-bungarotoxin binding site. Neither amino
      groups nor tyrosine residues were modified during the reaction with DEP,
      indicating that the derivatization of histidine residues is responsible for the
      observed effect. Faster-reacting residues appear to be involved in agonist
      induced ion flux through the nAChR channel. These results strongly support the
      connection between histidine residues and the receptor functional activity and
      lead us to infer that the changes observed in alpha-bungarotoxin binding and
      ionic channel capacity are the consequence of independent events induced by
      reaction with DEP.

PMID- 8746768
TI  - Synaptosomal and brain slice cerebrocortical [3H]L-glutamate uptake in a rat
      model of chronic hepatic encephalopathy.
AB  - Cerebrocortical [3H]L-glutamate uptake was examined using brain slices and
      synaptosomes obtained from rats with portal vein and bile duct ligation. In
      addition, the effect of in vitro addition of 5 mM ammonia on glutamate uptake
      parameters was determined. There was no significant difference in brain slice or
      synaptosomal glutamate uptake in rats with portal vein and bile duct ligation
      compared to control rats. In vitro addition of ammonia had no effect on uptake
      kinetics in either brain slices or synaptosomes. These results suggest that
      glutamate uptake kinetics are not perturbed in this animal model of chronic
      hepatic encephalopathy.

PMID- 8746769
TI  - Melatonin and deprivation myopia in chickens.
AB  - Chicken eyes elongate and become myopic if they are covered with translucent
      diffusors which degrade the retinal image ('deprivation myopia'). Since it has
      been shown that dopamine D2/D4 receptors (which mediate inhibition of melatonin
      synthesis) are also implicated in deprivation myopia, we have studied the role of
      melatonin in the visual control of eye growth. We have found that (1) diurnal
      melatonin rhythms and melatonin content in the retina are unchanged during
      deprivation myopia development despite the breakdown of both diurnal growth
      rhythms of the eye and diurnal rhythms in retinal dopamine metabolism, (2)
      diurnal melatonin rhythms and melatonin content in the retina remain unchanged
      after application of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) and
      presumably also after 6-hydroxydopamine (6-OHDA) application which both have a
      suppressive effect on deprivation myopia and (3) deprivation myopia was slightly
      reduced in both eyes after unilateral intravitreal injection of melatonin,
      despite that deprivation myopia is based on a mechanism intrinsic to the eye. We
      conclude that melatonin is not involved in the retinal signaling pathway
      translating visual experience to deprivation myopia.

PMID- 8746770
TI  - The effect of N-methyl-norsalsolinol on monoamine oxidase of the rat caudate
      nucleus in vitro.
AB  - The effects of N-methyl-norsalsolinol on basal and inhibited activity of
      monoamine oxidase (MAO) in membrane preparations from the caudate nucleus of the
      rat have been studied. For the first time, the physiological step of dopamine
      oxidation to 3, 4 dihydroxyphenylacetic aldehyde (DPAA) was examined. N-methyl
      norsalsolinol (2-MDTIQ) dose-dependently inhibited MAO activity with a IC50 of 33
      microM. The MAO inhibitors clorgyline and deprenyl were also found to inhibit
      formation of DPAA. In this case, the inhibition of these antagonists, clorgyline
      and deprenyl, was additive. N-methyl-norsalsolinol modified neither the enzyme
      inhibition induced by clorgyline nor by deprenyl. These results suggest that 2
      MDTIQ, the naturally occurring compound found in parkinsonian brain and
      cerebrospinal fluid, perturbs dopamine metabolism in basal ganglia.

PMID- 8746771
TI  - The source of brain adenosine outflow during ischemia and electrical stimulation.
AB  - Adenosine outflow and adenosine and adenine nucleotide content of hippocampal
      slices were evaluated under two different experimental conditions: ischemia-like
      conditions and electrical stimulation (10 Hz). Five minutes of ischemia-like
      conditions brought about an 8-fold increase in adenosine outflow in the following
      5 min during reperfusion, and a 2-fold increase in adenosine content, a 43%
      decrease in ATP, a 72% increase in AMP and a 30% decrease in energy charge (E.C.)
      at the end of the ischemic period. After 10 min of reperfusion ATP, AMP and E.C.
      returned to control values, while the adenosine content was further increased.
      Five minutes of electrical stimulation brought about an 8-fold increase in
      adenosine outflow that peaked 5 min after the end of stimulation, a 4-fold
      increase in adenosine content and an 18% decrease in tissue E.C. at the end of
      stimulation. After 10 min of rest conditions the adenosine content and E.C.
      returned to basal values. The origin of extracellular adenosine from S
      adenosylhomocysteine (SAH) was examined under the two different experimental
      conditions. The SAH hydrolase inhibitor, adenosine-2,3-dialdehyde (10 microM),
      does not significantly modify the adenosine outflow evoked by electrical
      stimulation or ischemia-like conditions. This finding excludes a significant
      contribution by the transmethylation pathway to adenosine extracellular
      accumulation evoked by an electrical or ischemic stimulus, and confirms that the
      most likely source of adenosine is from AMP dephosphorylation.

PMID- 8746772
TI  - Phosphorothioate oligodeoxynucleotides: antisense or anti-protein?

PMID- 8746773
TI  - Antiviral activity of an oligo(nucleoside methylphosphonate) that targets HSV-1
      immediate-early pre-mRNA 4,5 is augmented by cotreatment with replication
      defective adenovirus.
AB  - Replication-defective adenovirus p259A caused a 400-fold increase in the sequence
      specific antiherpetic activity of oligo(nucleoside methylphosphonate) (ONMP)
      IE4,5SA. Herpes simplex virus type 1 (HSV-1) growth was not inhibited in cells
      exposed to p259A in the absence of IE4,5SA or in cells cotreated with IE4,5SA and
      heated (10 minutes, 90 degrees C) p259A virus. Fluorescent microscopy of Vero
      cells treated with BODIPY-conjugated IE4,5SA revealed intracellular localization
      within endocytic-like vesicles with minimal cytoplasmic and intranuclear
      distribution. Diffuse staining over the entire cell was observed in cell
      cotreated with the BODIPY-conjugated IE4,5SA and p259A virus. This effect was not
      observed in cells cotreated with the BODIPY-conjugated ONMP and heated p259A
      virus. We interpret these findings to indicate that p259A augments IE4,5SA
      antiherpetic activity presumably via its ability to increase ONMP uptake and
      release from endocytic-like vesicles.

PMID- 8746774
TI  - Cellular uptake of oligodeoxyribonucleoside methylphosphonates.
AB  - The cellular uptake of oligodeoxyribonucleoside methylphosphonates has been
      evaluated using three radiolabeled oligomers. Oligomers I and II ([3H]-T8 and
      [3H]-T16, respectively) are nonionic methylphosphonate oligomers labeled with
      tritium on the phosphonate internucleotide linkage. EDA-III contains a single
      phosphodiester linkage, a [32P]-label and an ethylenediamine conjugate at the
      [32P]-5'-end. All three oligomers are stable in cells. At a 1 microM
      concentration, oligomer I is not taken up by human erythrocytes. The octanol/DPBS
      partition coefficients for oligomers I and II (1.5 x 10(-4) and 4.2 x 10(-4),
      respectively) further indicate that these molecules should not diffuse across
      cell membranes at appreciable rates. Oligomer I is taken up by HL-60 cells,
      although at a slower rate than the uptake of the fluid-phase marker sucrose. The
      cell-associated levels of oligomer II in K-562 cells following incubation of
      cells with the oligomer for 2 days is independent of concentration and
      nonsaturable, suggesting a mechanism of uptake independent of receptor. Finally,
      the initial uptake rate of EDA-III in mouse L cells is greater than the uptake of
      two oligodeoxyribonucleotides (T8, T16), reaching a plateau after 3 hours
      incubation with cells. These observations should aid in the elucidation of the
      mechanism by which this class of antisense agents enters the intracellular
      environment.

PMID- 8746775
TI  - Nonsequence-specific inhibition of bacterial luminescence by phosphorothioate
      oligodeoxyribonucleotides.
AB  - To evaluate the effect of synthetic DNA oligomers on regulation of bacterial
      genes in vivo, we tested 63 oligomers of variable length and chemistry for their
      ability to selectively suppress light production in the bioluminescent marine
      organism, Vibrio fischeri. Phosphodiester, phosphorothioate, and mixed backbone
      oligomers were designed to be lux gene targeted or nontargeted (negative)
      controls. Although significant suppression of luminescence was observed, most
      notably with the phosphorothioate oligomers, there was no correlation between
      inhibitory activity and oligomer sequence. The phosphorothioate oligomer that was
      most potent for inhibition of luminescence in bacterial culture had no effect on
      the activity of purified luciferase. Mechanisms other than sequence-specific
      inhibition of gene expression or direct interaction with luciferase are
      discussed.

PMID- 8746776
TI  - Phosphorothioate oligonucleotides reduce melanoma growth in a SCID-hu mouse model
      by a nonantisense mechanism.
AB  - In our efforts to investigate the biologic role of Ha-ras oncogenes in human
      melanoma by Ha-ras phosphorothioate antisense oligonucleotides, we observed that
      antisense, sense, and scrambled control oligonucleotides at a concentration of 10
      microM all similarly and strongly inhibited growth of our human melanoma target
      cell line SK-2 in vitro but without specific decrease of the target protein. Cell
      numbers with respect to the untreated control were reduced by 84% +/- 4.2% (ISD),
      82.9% +/- 3.6%, and 84% +/- 3%, respectively. In vivo studies in a SCID-hu mouse
      model confirmed these findings. Both antisense and sense control oligonucleotides
      administered through osmotic pumps significantly (p < 0.006) reduced the mean
      tumor weight (1.5 g +/- 0.4 g and 1.8 g +/- 0.8 g, respectively) in comparison
      with saline-treated (5.7 g +/- 0.7 g) or untreated control animals (5.8 g +/- 1.0
      g). The vascularity of oligonucleotide-treated tumors was greatly reduced.
      Clinical signs of oligonucleotide-related toxicity were not observed, and there
      was no evidence of histopathologic alterations in a variety of mouse tissues. We
      could demonstrate that the antimelanoma effects can be abrogated in vitro by
      adding basic fibroblast growth factor (bFGF). In the context of the importance of
      bFGF in melanocyte biology and angiogenesis, we argue in favor of an interaction
      between polyanionic phosphorothioate oligonucleotides and bFGF in our melanoma
      system. These findings stress the notion that phosphorothioate oligonucleotides
      may be promising antineoplastic lead compounds capable of employing antitumor
      effects by mechanisms other than specific inhibition of gene expression.

PMID- 8746777
TI  - Renal disposition characteristics of oligonucleotides modified at terminal
      linkages in the perfused rat kidney.
AB  - To clarify the renal disposition characteristics of oligonucleotides at the organ
      level, the renal handling of model end-capped oligonucleotides, 3'
      methoxyethylamine 5'-biotin-decathymidylic acid containing phosphoramidate
      modifications at 3'- and 5'-terminal internucleoside linkages (T10) and its
      phosphorothioate (Ts10), were studied in the perfused rat kidney. In a single
      pass indicator dilution experiment, venous outflow and urinary excretion patterns
      and tissue accumulation of radiolabeled oligonucleotides were evaluated under
      filtering or nonfiltering conditions. No significant binding to bovine serum
      albumin (BSA) in the perfusate was observed for T10, whereas more than 90% of
      Ts10 bound to BSA. The steady-state distribution volume of T10 calculated from
      the venous outflow pattern was larger than that of inulin, which corresponds to
      the extracellular volume of the kidney, whereas the distribution volume of Ts10
      was larger than that of BSA (the intravascular volume). These results suggested
      their interaction with the vascular wall. Rapid urinary excretion was observed
      for T10, similar to inulin used as a marker of golmerular filtration rate. On the
      other hand, urinary excretion of Ts10 was greatly restricted due to its high
      binding ability (> 90%) to BSA in the perfusate. A significant amount of T10 and
      Ts10 was accumulated in the kidney (T10, 1.8% of injected dose; Ts10, 1.3%)
      compared with inulin (0.2%) and BSA (< 0.1%). The accumulation of these
      oligonucleotides was ascribed to both tubular reabsorption and uptake from the
      capillary side. In addition, the uptake of T10 from the capillary side was
      significantly inhibited by simultaneous injection of dextran sulfate, suggesting
      that the oligonucleotide was taken up as an anionic molecule. These findings will
      be useful information for the development of delivery systems for antisense
      oligonucleotides.

PMID- 8746778
TI  - Antisense RNA-mediated inhibition of mouse hepatitis virus replication in L2
      cells.
AB  - We have successfully used antisense RNA to inhibit replication of the mouse
      hepatitis virus (MHV) in a cell culture system. MHV is a single-stranded RNA
      virus of positive polarity. Mouse L2 cells were stably transfected with an
      antisense construct that targets regions of genes 5 and 6 of the virus. High
      levels of expression from this construct, which is under control of the human
      elongation factor 1 alpha promoter, were found. After infection of the antisense
      cell lines with MHV, replication of the virus was significantly reduced compared
      with control cells. In a viral plaque assay, smaller plaques were found in the
      antisense cell lines. In addition, up to a 92% inhibition in the number of viral
      particles produced in one antisense cell line could be seen. This inhibitory
      effect decreased at longer (> 16 hour) infection times. It was possible to both
      increase the amount of inhibition and prolong the inhibitory effect by reducing
      the multiplicity of infection. Our results suggest that antisense RNA may be an
      effective tool to slow down progression of MHV infection in mice.

PMID- 8746779
TI  - The ade6 gene of the fission yeast as a target for antisense and ribozyme RNA
      mediated suppression.
AB  - A genetic system for the analysis of antisense and ribozyme mechanisms is a much
      needed experimental tool, and yeast represent a favorable organism on which to
      base such a system. We have shown previously that the fission yeast
      Schizosaccharomyces pombe has potential to satisfy the requirements of such a
      system. This report describes experiments designed to determine if antisense and
      ribozyme RNA-mediated gene suppression will be generally applicable to other
      genes in S. pombe. Antisense and ribozyme RNAs designed to suppress the ade6 gene
      were expressed at high levels from episomal expression vectors. The ade6 gene was
      chosen as a target as mutations within the gene confer adenine auxotrophy and a
      red colony phenotype, and it was expected that antisense or ribozyme RNA-mediated
      mutant phenocopies would exhibit the same readily detectable phenotype. No
      phenotypic indication of ade6 suppression was detected in transformed yeast, and
      ade6 target mRNA was analyzed by primer extension and Northern analysis.
      Initially, conflicting results were obtained from these techniques, which were
      determined to be due to duplex formation between antisense and target RNA in
      vitro. No detectable reduction in the ade6 mRNA levels was found, and it was
      concluded that the gene was not suppressed by the antisense or ribozyme RNAs
      tested. These results confirm that in S. pombe as with other organisms, the
      susceptibility of genes to RNA-mediated suppression may be gene specific and that
      design of antisense and ribozyme genes will be an empirical process.

PMID- 8746780
TI  - Regulation of mesothelial cell mitogenesis by antisense oligonucleotides for the
      urokinase receptor.
AB  - The association of urokinase-type plasminogen activator (uPA) with its receptor
      (uPAR) influences various biologic functions, including cell migration,
      angiogenesis, differentiation, and wound healing. Expression of uPAR at the
      mesothelial surface could, therefore, influence cellular responses in the pleural
      space. We found that a line of cultured human mesothelial cells (MeT5A) expressed
      specific and saturable binding sites for uPA that increased on stimulation with
      PMA. Ligand blotting studies showed that the mesothelial receptor is a 50 kD
      protein similar to that in other cell lines. Binding of active and intact, but
      not amino terminal or low molecular weight fragment, uPA to mesothelial cells
      enhanced DNA synthesis and cell proliferation, and antibodies against either the
      active site of uPA or uPAR abrogated this effect. We reasoned that regulation of
      uPAR expression could control uPA-induced mitogenesis and tested this hypothesis
      with antisense oligonucleotides complementary to uPAR mRNA. Phosphorothioate
      modified antisense oligonucleotides inhibited uPA-mediated mesothelial cell
      proliferation in a concentration-dependent manner. These effects were associated
      with decreased binding of 125I-uPA and reduced expression of the uPAR gene
      product. The results indicate that uPAR is involved in signal transduction
      pathways that control uPA-mediated mesothelial cell proliferation, a process
      implicated in the pathogenesis of mesothelial inflammation and pleural neoplasia.
      Antisense oligonucleotides to uPAR suppress mesothelial cell mitogenesis in vitro
      and offer a potential means of regulating the process in vivo.

PMID- 8746781
TI  - Lack of efficacy of interferon-alpha therapy in recurrent, advanced cervical
      cancer.
AB  - Human papillomavirus (HPV) is associated with 65-95% of in situ or early invasive
      squamous cell carcinomas of the cervix. A multiinstitutional, prospective phase
      II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG)
      to study the activity of IFN-alpha 2b in women with metastatic or locally
      recurrent cervix cancer. The activity of IFN-alpha 2b was correlated with the
      presence of HPV as measured by Southern blot hybridization or polymerase chain
      reaction techniques in 17 patients. All patients had failed prior definitive
      therapy with surgery, radiation, and chemotherapy. IFN-alpha 2b was administered
      at 10 MU/m2 subcutaneously three times per week. Among 31 patients enrolled, 3
      achieved a clinical response to treatment. Tumor was accessible for biopsy in 17
      patients. The presence of HPV was assayed by Southern blot hybridization (2 of
      17) and/or polymerase chain reaction (PCR) technology (15 of 17). Of the 17
      assays, 16 were informative. HPV was detected in 5 of 16 patients. Of 5 HPV
      positive women, 2 responded to treatment, versus 1 of 11 HPV-negative women, thus
      not permitting reliable statistical analysis. It is concluded that IFN-alpha 2b
      has only minimal activity against advanced, recurrent cervical cancer.

PMID- 8746782
TI  - Immunotherapy with low-dose interleukin-2 and interferon-gamma in a murine tumor
      model.
AB  - The aim of this study was to evaluate the therapeutic efficacy of locally
      administered low-dose interleukin-2 (IL-2) alone or together with interferon
      gamma (IFN-gamma) in a herpes simplex virus type 2-transformed murine (H238)
      fibrosarcoma model. In vitro incubation showed that IL-2, but not IFN-gamma, had
      a significant inhibitory effect on DNA synthesis in H238 cells. In vivo
      experiments were performed with BALB/c mice to determine the optimal time of
      treatment with each cytokine after subcutaneous (sc) tumor implantation. The
      greatest antitumor effect with IL-2 (1 x 10(5) total international units, sc) was
      noted when treatment was administered during the first week after tumor
      injection, whereas with IFN-gamma (500 total units, intraperitoneally) treatment
      during the second week proved best. Combination of the two agents produced
      complete tumor regression in 44.4% of mice; regression with single-modality
      treatment was 0-11%. The presence of H238 tumor induced splenomegaly and enhanced
      the oxidative burst capacity of phagocytes. Peripheral blood leukocyte counts
      were low in tumor-bearing groups, regardless of treatment. IL-2 and IFN-gamma
      were nondetectable in the plasma of tumor-bearing or control mice; however, total
      TGF-beta 1 was 248% higher with IL-2 treatment compared with tumor-bearing
      nontreated controls. These results show that IL-2 and IFN-gamma can significantly
      inhibit the growth of highly aggressive H238 tumors and support further
      investigations with these agents.

PMID- 8746783
TI  - Induction of apoptotic nuclei by interferon-gamma and by predesquamin in cultured
      keratinocytes.
AB  - Predesquamin is a glycoprotein found in the transition layer and the lower
      stratum corneum of human epidermis. Interferon-gamma (IFN-gamma) induces the
      synthesis of predesquamin by keratinocytes in culture. We now show
      ultrastructurally that exogenous addition of either predesquamin or IFN-gamma to
      cultured keratinocytes induces apoptotic nuclei with condensed chromatin.
      Degradation of cellular DNA is also evident as a ladder pattern in an agarose
      gel. After incubation with both predesquamin and IFN-gamma (but not either
      alone), the mobility of plasmid DNA in a gel shows retardation specific for
      guanine residues. This binding to the DNA may impart to it a conformational
      change that facilitates access by endogenous cellular nucleases. In epidermal
      cells cultured with IFN-gamma supplementation, we also show by RT-PCR that there
      is an upregulation of the genes c-myc, p53, gadd45, dsRNA-activated protein
      kinase, and 2'-5'-oligo(A)-dependent RNase, which have all been implicated in
      apoptosis in other cell types. These results are pertinent to the mechanism of
      occurrence of apoptosis in the epidermis in vivo, where predesquamin and IFN
      gamma are endogenous. Programmed cell death is an inherent step in the terminal
      differentiation and desquamation of the epidermis.

PMID- 8746784
TI  - NF kappa B and interferon regulatory factor 1 physically interact and
      synergistically induce major histocompatibility class I gene expression.
AB  - Major histocompatibility (MHC) class I gene expression is synergistically induced
      by the cytokines TNF-alpha and IFN-gamma. However, the mechanism that results in
      synergistic activation of these genes has remained unclear. We demonstrated here
      that TNF-alpha induced binding of NF kappa B p50 and p65 to the NF kappa B-like
      element of the MHC class I promoter termed region I and IFN-gamma induced binding
      of IRF-1 to the adjacent interferon consensus sequence (ICS). We further
      demonstrated that NF kappa B and IRF-1 physically interacted with each other and
      cooperatively induced MHC class I gene expression when cotransfected into CHP-126
      neuroblastomas. These results provide a molecular mechanism by which TNF-alpha
      and IFN-gamma synergistically induce the expression of a variety of genes
      involved in immune responses, including MHC class I.

PMID- 8746785
TI  - Potential application of human interferon-alpha in microbial infections of the
      oral cavity.
AB  - We have been evaluating the potential use of interferon-alpha (IFN-alpha) against
      fungal infections of the oral cavity. IFN-alpha has been reported to enhance the
      antifungal activity of neutrophils. This cytokine is also known to synergize with
      interleukin-1 in enhancing a number of immunomodulatory responses. To study
      cytokine involvement in oral defense mechanisms against microbial infection, we
      first demonstrated the presence of antimicrobial interleukins (IL)-1 alpha, IL-1
      beta, and IL-8 in the saliva, which can all augment the microbicidal activity of
      neutrophils, and the presence of epithelial cells and neutrophils in oral lavage
      fluid from healthy volunteers. Immunostaining for cytokines produced by these
      cells showed that the candidate producers of both IL-1 alpha and IL-8 are
      epithelial cells, but those of IL-1 beta remained inconclusive. We next found
      that IFN-alpha enhanced IL-1 alpha-augmented neutrophil-mediated anticandidal
      action while marginally enhancing IL-8- and IL-1 beta-mediated reactions. These
      results suggest that IFN-alpha is a potential agent for treating oral mycosis by
      cooperating with endogenous cytokine(s) in the saliva, in addition to its
      intrinsic antiviral action.

PMID- 8746786
TI  - A three-dimensional model of interferon-tau.
AB  - The interferon-tau (IFN-tau) are type I IFN whose expression is restricted to the
      embryonic trophectoderm of the developing placenta of ruminant ungulate species,
      where they act as hormones of pregnancy. Here computer modeling has been used to
      generate homology models of bovine and ovine IFN-tau based on the refined crystal
      structure of murine IFN-beta. The IFN-tau structure, like that of MuIFN-beta, is
      based on five long alpha helices (A-E), one short helix in the middle of the loop
      connecting helices C and D and a long loop between helices A and B. BoIFN-tau
      differs from MuIFN-beta in three important respects. First, as in all IFN-tau,
      there is a carboxyl tail of nine amino acids that cannot be accurately modeled
      but that would have a length of approximately 30 A when fully extended. Second,
      like the IFN-alpha subtype, all IFN-tau have a three-amino acid insertion in loop
      AB and a likely disulfide bridge between Cys29 and Cys139 that lead to marked
      conformational differences between them and MuIFN-beta in a region (Leu22 to
      Arg33 in IFN-tau) believed to interact with the receptor. Third, all IFN-tau, as
      well as the related IFN-omega, possess a Gly at position 126 (rather than the
      equivalent Arg on MuIFN-beta and IFN-alpha) that will impair an extensive
      hydrogen bonding interaction between helix D and loop AB. As a result, the
      polypeptide segment around this region (Phe36 to Gln40) of loop AB is likely to
      be considerably more flexible than in other type I IFN.

PMID- 8746787
TI  - Serum interleukin-6 levels in the steady state of sickle cell disease.
AB  - In patients with childhood sickle cell disease (SCD) serum interleukin-6 (IL-6)
      levels were measured during the steady (healthy) state of disease. The
      corresponding measurements were made in comparable healthy normal controls. Serum
      IL-6 levels were assessed via ELISA in 27 SCD patients and 19 controls. Results
      revealed significantly higher circulating levels of IL-6 in the SCD patients (60
      +/- 7 pg/ml) compared with the healthy controls (12 +/- 5 pg/ml). IL-6 is a
      multifunctional cytokine that plays a central role in host defense mechanisms.
      The impact of high circulating levels of IL-6 may be deleterious to humoral and
      cell-mediated immune functions in SCD, with resultant heightened risk for
      morbidity.

PMID- 8746788
TI  - Type I and type II interferons upregulate functional type I interleukin-1
      receptor in a human fibroblast cell line TIG-1.
AB  - The regulation of type I interleukin-1 receptor (IL-1R) expression by type I,
      interferon (IFN)-alpha A/D, and type II IFN, IFN-gamma, in a human fibroblast
      cell line TIG-1 was investigated. After 2 h stimulation with human IFN-alpha A/D
      or IFN-gamma, the levels of type I IL-1R mRNA increased. We previously reported
      that IL-1 upregulates transcription and cell surface molecules of type I IL-1R in
      TIG-1 cells through induction of prostaglandin (PG) E2 and cAMP accumulation.
      However, indomethacin was unable to inhibit the effect of IFNs, indicating that
      IFNs augment IL-1R expression through a pathway distinct from that of IL-1. The
      augmentation was also observed in other fibroblast cell lines. Nuclear run-on
      assays and studies of the stability of mRNA suggested that the increase in IL-1R
      mRNA was a result of the enhanced transcription of IL-1R gene. Binding studies
      using 125I-IL-1 alpha revealed that the number of cell surface IL-1R increased
      with no change in binding affinity by treatment with these IFNs. Pretreatment of
      the cells with IFNs enhanced IL-1-induced IL-6 production, indicating that IFNs
      upregulate functional IL-1R. IL-1 and IFNs are produced by the same cell types,
      as well as by the adjacent different cell types, and are concomitantly present in
      lesions of immune and inflammatory reactions. These results therefore suggest
      that IFNs exhibit synergistic effects with IL-1 through upregulation of IL-1R.
      Augmented production of IL-6 may also contribute to the reactions.

PMID- 8746789
TI  - Recombinant human transforming growth factor beta does not inhibit the effects of
      interleukin-1 beta on pancreatic islet cells.
AB  - The macrophage-derived cytokine, interleukin-1 beta (IL-1 beta), has been
      implicated to play an important role in the autoimmune beta cell lesion of
      insulin-dependent diabetes mellitus (IDDM) because of its inhibition of insulin
      secretion, direct cytotoxicity, and alteration of islet cell antigen expression.
      Because transforming growth factor beta (TGF-beta) has been reported to inhibit
      IL-1 receptor expression in several lymphoid and progenitor cell lines, to induce
      IL-1 receptor antagonist protein (IRAP) production in human peripheral blood
      monocytes, and to antagonize several effects of inflammatory cytokines and
      because oral tolerance may be mediated in part by TGF-beta released by regulatory
      T lymphocytes, we investigated whether TGF-beta counteracted the effects of IL-1
      beta on islet cells. Islets isolated from Sprague-Dawley rats were cultured with
      or without recombinant human IL-1 beta and TGF-beta. Accumulated insulin
      secretion, cytokine-induced cytotoxicity, and islet cell expression of glutamic
      acid decarboxylase 65 (GAD-65) and heat-shock protein 70 (HSP-70) were measured
      in this study. We found that (1) IL-1 beta at 50 and 100 pg/ml inhibited insulin
      secretion by 41.9 +/- 14.8 and 52.6 +/- 3.5% and induced cytotoxicity by 46.5 +/-
      17.3 and 54.1 +/- 6.1%, respectively. IL-1 beta at 1000 pg/ml significantly
      increased HSP-70 expression and decreased GAD-65 expression. (2) TGF-beta at 0.1,
      1, 10, and 40 ng/ml had no significant effect on insulin secretion and did not
      induce cytotoxicity, TGF-beta at 40 ng/ml had no effect on the expression of
      either HSP-70 or GAD-65. (3) In combination, TGF-beta at 1, 10, and 40 ng/ml did
      not antagonize the IL-1 beta (50 and 100 pg/ml)-induced inhibition of insulin
      secretion or cytotoxicity; TGF-beta (40 ng/ml) did not block the effects of IL-1
      beta (1000 pg/ml) on HSP-70 or GAD-65 expression. In conclusion, recombinant
      human TGF-beta does not counteract these effects of recombinant human IL-1 beta
      on rat pancreatic islet cells.

PMID- 8746790
TI  - An interleukin-1 binding region oligopeptide from the human type I IL-1 receptor
      reduces acute inflammation, delayed hypersensitivity reaction, and lethal
      endotoxemia in animals.
AB  - The effect of an interleukin-1 binding region oligopeptide from the interleukin-1
      receptor on various inflammatory responses was investigated in animal models. A
      synthetic peptide (KICIRIQIS) corresponding to 86-93 of the extracellular domain
      of the human type I interleukin-1 receptor was used. Carrageenan-induced rat paw
      edema, a model of acute inflammation, was dose dependently suppressed by
      intraperitoneal administration of the peptide. The delayed hypersensitivity
      reaction to sheep red cells was diminished by pretreatment of mice with the
      peptide at a relatively high dose. In a murine lethal endotoxemia model, animals
      treated with the interleukin-1 receptor peptide (10 mg/kg x 4) showed
      significantly better survival than vehicle-treated animals when the peptide was
      administered from 20 minutes after lipopolysaccharide injection. Improved
      survival was accompanied by suppression of lipopolysaccharide-induced production
      of colony-stimulating factor, although the peptide did not improve hypoglycemia.
      These findings suggest that the interleukin-1 receptor peptide may be a potential
      treatment for various inflammatory processes.

PMID- 8746791
TI  - Dual modulation by l-leucovorin and recombinant human interferon alpha 2a of 5
      fluorouracil antitumor activity against the human colon carcinoma xenograft Co-4.
AB  - We investigated the dual modulation by l-leucovorin (LV) and recombinant human
      interferon-alpha 2a (IFN-alpha 2a) of 5-fluorouracil (5-FU) antitumor activity
      against human colon carcinoma cells (Co-4) using a nude mouse system. 5-FU was
      administered intraperitoneally (IP) at 10 or 90 mg/kg. 5-FU (10 mg/kg) was
      administered daily for 10 days, and 90 mg/kg was administered once. LV was
      administered IP 1 and 0 h before 5-FU treatment at 200 mg/kg. IFN-alpha 2a was
      administered subcutaneously (SC) daily for 14 days at 60,000 IU/mouse. When 5-FU
      was administered at 10 or 90 mg/kg with these two modulators, the antitumor
      effect was increased significantly, with T/C ratios of 18.1 and 6.1,
      respectively. These modulatory effects were assessed as synergistic, without
      associated severe side effects or death during the experimental period. LV
      augmented the antitumor activity of 5-FU through increment of thymidylate
      synthetase (TS) inhibition, and IFN-alpha 2a showed a modulatory effect in
      elevating the intratumoral concentration of fluorouridine without change in TS
      inhibition. These results suggest that 5-FU antitumor activity against human
      colon carcinoma could be significantly potentiated without severe side effects by
      these two modulators, which possess different modes of action.

PMID- 8746792
TI  - Polymerase chain reaction cloning and expression of the rat granulocyte
      macrophage colony-stimulating factor.
AB  - We used reverse transcription-polymerase chain reaction (RT-PCR) to clone a rat
      complementary DNA that encoded the PVG rat granulocyte-macrophage colony
      stimulating factor (GM-CSF). PCR products were cloned into a eukaryotic
      expression vector and transfected into the mouse myeloma cell line Sp2/0-Ag14.
      Cell culture supernatants of two of these transfectants supported proliferation
      of the growth factor-dependent cell line, DA-3, and promoted myeloid colony
      formation in rat and mouse bone marrow cell (BMC) cultures. The GM-CSF activity
      in these supernatants was neutralized by a polyclonal antibody to mouse GM-CSF.
      The cloning and expression of rat GM-CSF provides a valuable reagent for the
      study of the biology and clinical applications of the GM-CSFs.

PMID- 8746793
TI  - Cloning and expression of canine interleukin-10.
AB  - We describe here the cloning of canine IL-10 cDNA (GenBank accession No. U33843)
      and the expression of recombinant IL-10 in a dog kidney cell line (DK6247) and
      Chinese hamster ovary cells (CHO). Canine IL-10 exhibits strong sequence homology
      to the known sequences of human, mouse, rat, and bovine genes at nucleotide and
      amino acid levels. The IL-10 gene, when introduced into DK and CHO cell lines,
      produces recombinant IL-10 that causes an inhibitory effect on allogeneic MHC
      driven lymphoproliferative responses.

PMID- 8746794
TI  - A bivalent immunoadhesin of the human interferon-gamma receptor is an effective
      inhibitor of IFN-gamma activity.
AB  - We describe here the bioengineering of a bivalent IFN-gamma-RFc immunoadhesin
      consisting of the extracellular domain of the human IFN-gamma receptor alpha
      chain (IFN-gamma-R) fused to a human IgG1 Fc region (encoding hinge, CH2 and CH3
      domain) that was efficiently expressed as a covalently linked homodimer in insect
      cells and purified in a one-step purification procedure. The IFN-gamma-RFc fusion
      protein exerted a 3-fold higher ligand binding affinity in binding competition
      studies in vitro compared with the monovalent extracellular IFN-gamma-R domain.
      In addition, the in vitro antagonistic activity of IFN-gamma-RFc, as determined
      by inhibition of IFN-gamma-induced virus protection and HLA-DR expression, was
      more than 30-fold higher in comparison with the monovalent soluble receptor. The
      described IFN-gamma-R immunoadhesin is a potential therapeutic reagent to
      interfere with the disease-promoting activities of IFN-gamma in several
      autoimmune diseases.

PMID- 8746795
TI  - Age does not alter Protein kinase C isozymes mRNA expression in rat brain.
AB  - Calcium and phospholipid dependent Protein kinase C (PKC) may play a role in
      memory function and pathogenesis of many neurodegenerative disorders such as
      Alzheimer's disease (AD). Abnormal phosphorylation by PKC as well as reduced
      levels of PKC has been implicated in the neurodegeneration associated with AD and
      aging. Recently, many subtypes of PKC isozymes have been identified by molecular
      biology techniques which are expressed differentially in various regions of the
      brain. The reduction and alterations in the activities and distribution of these
      subtypes of PKC isozymes may be accountable for the decline of selective neurons
      during aging. In order to investigate the role of PKC isozymes during aging, we
      examined the distribution of PKC-alpha, beta, and gamma mRNA expressions between
      young (4 months) and old (25 months) rat brains using in situ hybridization
      histochemistry. Our studies showed that signals of three isoforms of PKC mRNA
      vary in cortical and hippocampal regions. However, no change was detected in any
      of the PKC isoforms mRNA expression in aged animals.

PMID- 8746796
TI  - Effects of pinealectomy and melatonin treatments on serotonin uptake and release
      from synaptosomes of rat hypothalamic regions.
AB  - This study examined the effects induced by long-term pinealectomy, daily
      melatonin treatment to pinealectomized and intact rats, and a single melatonin
      injection on [14C]-serotonin (5-HT) uptake and release from synaptosomes obtained
      of hypothalamic regions. Pinealectomy inhibited the accumulation of labeled 5-HT
      by synaptosomes of the preoptic area-anterior hypothalamus (POA-AH), but it
      failed to alter the [K+]-evoked 5-HT release. Melatonin treatment for 10
      consecutive days to pinealectomized rats restored 5-HT uptake in POA-AH, and also
      increased 5-HT release in medial and posterior hypothalamus. These results
      suggest that pineal melatonin plays a stimulatory role on the serotoninergic
      terminals of the hypothalamus. Moreover, when daily melatonin treatment was
      administered to intact rats a significant increase in 5-HT uptake activity by
      synaptosomes of all the hypothalamic regions was observed, but 5-HT release was
      unaffected. In contrast, a single melatonin injection induced a significant
      decrease in 5-HT release from synaptosomes of the POA-AH was observed. The
      results suggest the existence of a differential sensitivity in the mechanisms
      mediating melatonin actions on 5-HT uptake/release, which depends on the presence
      of the pineal gland in the animals and on the frequency of the treatments with
      the pineal hormone.

PMID- 8746797
TI  - Glutamine synthetase gene expression in a glioblastoma cell-line of clonal
      origin: regulation by dexamethasone and dibutyryl cyclic AMP.
AB  - We investigated the expression of glutamine synthetase (GS), an enzyme involved
      in astroglial metabolism and marker of astroglial functional maturity, in a
      glioblastoma cell-line (GL-15) of clonal origin. In spite of their phenotypic
      immaturity, evidenced in a mosaic fashion by a poor glial fibrillary acidic
      protein (GFAP) expression, the level of GS-mRNA is high in GL15 cells and the
      considerable amount of GS biological activity can be further induced and
      stabilized by glucocorticoids. A correlation between the induction by
      dexamethasone of the GS-mRNA level and the GS biological activity suggests a
      transcriptional regulation of GS expression by the aforesaid hormone. Under this
      hormonal action, changes in cell morphology occur and they are correlated with an
      overexpression of the GFAP, a marker of astroglial differentiation. On the
      contrary, dibutyryl cyclic AMP (dbc AMP) down-regulates the GS-mRNA expression
      and decreases GS activity. These results suggest that GL-15 cells have a common
      glucocorticoid dependent mechanism able to induce GS and GFAP as well as
      morphological changes. However in these cells AMPc responsive elements are
      involved in the negative modulation of the GS expression, contrary to what occurs
      in normal astroglial cells.

PMID- 8746798
TI  - Uptake of 75-Selenium into the central nervous system of the rat.
AB  - These experiments have investigated selenium movement between blood and the CNS
      in anaesthetized rats. Each animal was anaesthetized and the left femoral blood
      vessels cannulated for blood withdrawal and solute infusion. Each rat received 75
      Se as sodium selenite infused in normal saline and experiments lasted between 5
      minutes and 5 hours during which blood samples were periodically taken. At
      termination, the CNS was removed, dissected and analysed with the plasma samples
      for 75-Se radioactivity by gamma-counting. Data were analyzed by multiple-time
      uptake analysis. Results showed unidirectional uptake of 75-Se into the CNS and
      some regional differences were found. On average the CNS influx rate constant
      (Kin) was about 7 +/- 1 x 10(-5) ml/min/g. This indicates that the 75-Se most
      likely entered the CNS in a protein-bound form.

PMID- 8746799
TI  - Further studies on the mechanism of action of substance P in rat brain, involving
      selective phosphatidylinositol hydrolysis.
AB  - We have suggested that substance P, in cerebral cortex, causes a
      phosphatidylinositol (PI) breakdown by a dual mechanism suggesting the
      involvement of either phospholipase A2 or phospholipase C. We have presently
      characterized further these effects. Substance P (65 pM) provoked an increase in
      lysoPI concomitant with a decrease in PI level. This finding confirms the
      involvement of phospholipase A2 activation. To study the involvement of
      phospholipase C in the action of higher doses (0.65 microM) of the peptide, we
      used pulse-chase experiments (where phospholipid depletion was monitored) and
      short-term 32P-labeled slices (where phospholipid synthesis was studied).
      Substance P evoked an acceleration of both hydrolysis and resynthesis of PI as
      early as 15 s. A prolonged exposure (30 min) resulted in stimulation of PI
      hydrolysis without subsequent resynthesis. The peptide did not cause any effect
      on inositol 1,4-bisphosphate and inositol 1,4,5-trisphosphate. These alterations
      in PI metabolism take place simultaneously with a generation of diacylglycerol
      which showed two maxima at both indicated times.

PMID- 8746800
TI  - Loss of [3H]kainate and of NMDA-displaceable [3H]glutamate binding sites in brain
      in thiamine deficiency: results of a quantitative autoradiographic study.
AB  - Previous studies suggest that alterations of brain glutamate synthesis and
      release occur in experimental thiamine deficiency. In order to assess the
      integrity of post-synaptic glutamatergic receptors in thiamine deficiency,
      binding sites for [3H]glutamate (displaced by NMDA), [3H]-kainate, and
      [3H]quisqualate (AMPA sites) were evaluated using Quantitative Receptor
      Autoradiography in rat brain following 14 days of treatment with the central
      thiamine antagonist pyrithiamine. Compared to pair-fed controls, brains of
      symptomatic thiamine-deficient animals contained significantly fewer NMDA
      displaceable binding sites in cerebral cortex, medial septum and hippocampus. It
      has been suggested that NMDA-receptor mediated glutamate excitotoxicity plays a
      role in the pathogenesis of neuronal loss in thiamine deficiency. If such is the
      case, the selective loss of NMDA binding sites in cerebral cortex and hippocampus
      offers a possible explanation for the relative nonvulnerability of these brain
      regions to pyrithiamine-induced thiamine deficiency. [3H]quisqualate (AMPA)
      binding sites were unchanged in all brain regions of pyrithiamine-treated rats
      whereas [3H]kainate sites were significantly reduced in density in medial and
      lateral thalamus. The decline in these binding sites may be due to neuronal loss
      in pyrithiamine-induced thiamine deficiency. Alterations of glutamatergic
      synaptic function involving both NMDA and kainate receptor subclasses could
      contribute to the pathogenesis of neurological dysfunction in Wernicke's
      Encephalopathy in humans.

PMID- 8746801
TI  - Structural alterations in synaptosomal membrane-associated proteins and lipids by
      transient middle cerebral artery occlusion in the cat.
AB  - We have previously reported that ischemia reperfusion injury results from free
      radical generation following transient global ischemia, and that this radical
      induced damage is evident in the synaptosomal membrane of the gerbil. [Hall et
      al, (1995) Neuroscience 64: 81-89]. In the present study we have extended these
      observations to transient focal ischemia in the cat. We prepared synaptosomal
      membranes from frontal, parietal-temporal, and occipital regions of the cat
      cerebral cortex with reperfusion times of 1 and 3 hours following 1 hour right
      middle cerebral artery occlusion. The membranes were selectively labeled with
      protein and lipid specific paramagnetic spin labels and analyzed using electron
      paramagnetic resonance spectrometry. There were significant motional changes of
      both the protein and lipid specific spin labels in the parietal-temporal and
      occipital regions with 1 hour reperfusion; but, both parameters returned to
      control values by 3 hours reperfusion. No significant changes were observed in
      the normally perfused frontal pole at either reperfusion time. These results
      support the argument that free radicals play a critical role in cell damage at
      early reperfusion times following ischemia.

PMID- 8746802
TI  - Kainate receptor modification in the fetal guinea pig brain during hypoxia.
AB  - The present study tests the hypothesis that hypoxia alters the high-affinity
      kainate receptors in fetal guinea pig brain. Experiments were conducted in
      normoxic and hypoxic guinea pig fetus at preterm (45 days of gestation) and term
      (60 days of gestation). Hypoxia in the guinea pig fetus was induced by exposure
      to maternal hypoxia (FiO2 = 7%) for 60 min. Brain tissue hypoxia in the fetus was
      documented biochemically by decreased levels of ATP and phosphocreatine. [3H]
      Kainate binding characteristics (Bmax = number of receptors, Kd = dissociation
      constant) were used as indices of kainate receptor modification. P2 membrane
      fractions were prepared from the cortex of normoxic and hypoxic fetuses and were
      washed six times prior to performing the binding assays. [3H]kainate binding was
      performed at 0 degrees C for 30 min in a 500 microliters medium containing 50 mM
      Tris-HCl buffer, 0.1 mM EDTA (pH 7.4), 300 micrograms protein and varying
      concentrations of radiolabelled kainate ranging from 1 to 200 nM. Non-specific
      binding was determined in the presence of 1.0 mM glutamate. During brain
      development from 45 to 60 days gestation, Bmax value increased from 330 +/- 16 to
      417 +/- 10 fmoles/mg protein; however, the Kd was unchanged (8.2 +/- 0.4 vs 8.8
      +/- 0.5 nM, respectively). During hypoxia at 60 days, the Kd value significantly
      increased as compared to normoxic control (15.5 +/- 0.7 vs 8.8 +/- 0.5 nM,
      respectively), whereas the Bmax was not affected (435 +/- 12 vs 417 +/- 10
      fmol/mg protein, respectively). At 45 days, hypoxia also increased the Kd (11.9
      +/- 0.6 vs 8.2 +/- 0.4 nM) without affecting the Bmax (290 +/- 15 vs 330 +/- 16
      fmol/mg protein, respectively). The results show that the number of kainate
      receptors increase during gestation without change in affinity and demonstrate
      that hypoxia modifies the high-affinity kainate receptor sites at both ages;
      however the effect is much stronger at 60 days (term). The decreased affinity of
      the site could decrease the kainate receptor-mediated fast kinetics of
      desensitization and provide a longer period for increased Na(+)-influx, leading
      to increased accumulation of intracellular Ca2+ by reversal of the Na(+)-Ca2+
      exchange mechanism. In addition, Kd values for kainate-type glutamate receptor
      sites are 30-40 fold lower (i.e. higher affinity) than those for NMDA
      displaceable glutamate sites. The higher affinity suggests that the activation of
      the kainate-type glutamate receptor during hypoxia could precede initiation of
      NMDA receptor-mediated excitotoxic mechanisms. We propose that hypoxia-induced
      modification of the high affinity kainate receptor in the fetus is a potential
      mechanism of neuroexcitotoxicity.

PMID- 8746803
TI  - Simultaneous measurement of biogenic amines and their metabolites in rat brain
      regions after acute administration of and abrupt withdrawal from butorphanol or
      morphine.
AB  - Changes in levels of biogenic amines and metabolites were measured using high
      performance liquid chromatography fitted with an electrochemical detection in
      various rat brain regions after acute administration of and abrupt withdrawal
      from continuous intracerebroventricular infusion of butorphanol (a mu/delta/kappa
      mixed opioid receptor agonist) or morphine (a mu-opioid receptor agonist). A
      single dose of butorphanol (26 nmol/5 microliters) or morphine (26 nmol/5
      microliters) increased levels of 3,4-dihydroxyphenylacetic acid in the striatum
      and limbic region and of homovanilic acid in the cortex, striatum, and limbic
      region. In animals which had been infused with butorphanol (26
      nmol/microliters/hr) or morphine (26 nmol/microliters/hr) for 3 days, an increase
      in dopamine turnover was observed. The levels of 3,4-dihydroxyphenylacetic acid
      was decreased and that of homovanilic acid was increased in the striatum, limbic
      region, and midbrain immediately after termination of opioid infusion. Both
      dopamine metabolites (in these areas) were decreased at 2 and 6 hr after
      butorphanol or morphine withdrawal. Changes in norepinephrine, serotonin, and 5
      hydroxyindoleacetic acid levels in some brain regions were observed in the
      morphine-, but not in butorphanol-dependent rats. These data suggest that the
      increase and the decrease in dopaminergic activity, but not noradrenergic and
      serotonergic neurons, in the some brain regions are closely associated with the
      production of antinociception of and the expression of withdrawal syndrome from
      butorphanol and morphine, respectively.

PMID- 8746804
TI  - Release of ciliary neurotrophic factor from cultured astrocytes and its
      modulation by cytokines.
AB  - CNTF rescues various types of lesioned neurons in vivo, and it needs to be
      released from astrocytes into the extracellular space to have the effect.
      However, direct evidence for CNTF release has not been unequivocally
      demonstrated. We hypothesized that the rapid sequestration by CNTF receptor
      present on cultured astrocytes might be the cause of the inability to detect CNTF
      released into astrocyte-conditioned medium (ACM). Therefore, we measured CNTF
      immunoreactivity in medium conditioned by astrocytes treated with
      phosphatidylinositol-specific phospholipase C (PI-PLC) which was used to prevent
      released CNTF from binding to the CNTF receptor, since PI-PLC cleaves glycosyl
      phosphatidylinositol anchor of CNTFR alpha, the unique component involved in CNTF
      binding. CNTF was not detectable in untreated ACM, but was detectable in PI-PLC
      treated ACM. These results together with the evidence that PI-PLC treatment did
      not have a toxic effect on astrocytes prove the fact that CNTF can be released
      from astrocytes without cell lysis. Subsequently, the effect of cytokines such as
      IL-1 beta, TNF-alpha, and EGF on CNTF release was examined. These cytokines
      increased CNTF protein levels in ACMs without increasing CNTF protein levels in
      astrocyte-extracts, indicating that they enhanced CNTF release from astrocytes.

PMID- 8746805
TI  - Alteration of transglutaminase activity in rat and human spinal cord after
      neuronal degeneration.
AB  - We measured the activity of transglutaminase (TG), a Ca(2+)-dependent enzyme and
      a biochemical marker of cell degeneration, in the adult rat spinal cord after
      unilateral occlusion of a branch of the dorsal spinal artery, and compared it to
      the enzyme activity in the tissue on the contralateral side without ischemic
      damage. The affected half of the spinal cord showed a significant rise in
      intrinsic (endogenous) TG activity one day after ischemic insult while no
      apparent morphological changes were observed in the tissue. However, the enzymic
      activity on the affected side gradually decreased to reach the level in the non
      affected tissue, accompanying severe degeneration of neuronal cells at 7 days
      after the surgery, then it declined to nearly half the level in the intact tissue
      30 days after the operation. We also determined the TG activity in transverse
      sections of the human spinal cord obtained at autopsy from 5 amyotrophic lateral
      sclerosis (ALS) and 9 non-ALS patients. TG activity in thoracic and lumbar cords
      was markedly low in ALS patients not only in ventral and lateral regions but also
      in the dorsal portion. These findings imply that the reduced TG activity in the
      ALS spinal cord is one of the characteristic features of the disease reflecting
      exhaustion of the enzyme in the tissue resulting from degeneration of the spinal
      neurons through cross-linkage of soluble intraneuronal cytoplasmic proteins.

PMID- 8746806
TI  - The influence of glycine and related compounds on spinal cord injury-induced
      spasticity.
AB  - Spasticity is a frequent and complex sequel to spinal cord injury. The
      neurochemical basis for the origin of spasticity is largely unknown. Glycine is
      among the most abundant neurotransmitters in the spinal cord. However, the role
      of glycine and related compounds in spasticity have received little attention. An
      ischemic spinal cord injury was created in rabbits, by an intraaortic balloon
      occlusion technique, which produced lower limb spasticity. A catheter was
      inserted into the cisterna magna and the spinal cord was bathed with 100 microM
      solutions of glycine, strychnine, D-serine, beta-alanine, MK-801, or artificial
      CSF for 4 hours at a rate of 10 microliters/min. H-reflexes were monitored before
      and during infusion by stimulating the posterior tibial nerve and recording from
      the plantar surface of the foot. Glycine, D-serine, and MK-801 depressed the H
      wave, strychnine produced a heightened H wave, and beta-alanine caused no
      significant changes. These results indicate that glycine and related compounds
      may influence spasticity.

PMID- 8746807
TI  - Effect of prenatal treatment with methylazoxymethanol on carbachol-,
      norepinephrine- and glutamate-stimulated phosphoinositide metabolism in the
      neonatal, young, and adult offspring.
AB  - Carbachol-, norepinephrine- and glutamate-stimulated phosphoinositide metabolism
      was investigated in the neonatal, young and adult cerebral cortex slices of rats
      prenatally treated with methylazoxymethanol (MAM) on gestational day 15 (GD15) or
      GD19. In rat offspring treated on GD15 there was a significant reduction in the
      accumulation of [3H]inositol phosphates induced by carbachol and a significant
      increase in the accumulation of [3H]inositol phosphates induced by norepinephrine
      on day 7, whereas no changes were observed at the other ages. No significant
      changes, on the other hand, were observed for glutamate-stimulated
      phosphoinositide metabolism in GD15 treated rats and for carbachol-,
      norepinephrine- and glutamate-stimulated phosphoinositide metabolism in animals
      treated on GD19 at any of the different ages evaluated. These results indicate
      that treatment with MAM on GD15, which results in a marked microencephaly, causes
      a marked alteration of muscarinic and alpha 1-adrenergic receptor-stimulated
      phosphoinositide metabolism during brain development and that these alterations
      undergo adaptive changes in the adult brain.

PMID- 8746808
TI  - Short-term manganese pretreatment partially protects against 1-Methyl-4-phenyl
      1,2,3,6-tetrahydropyridine neurotoxicity.
AB  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that induces
      parkinsonism in human and non-human primates. Its mechanism of action is not
      fully elucidated. Recently, the participation of trace metals, such as manganese,
      on its neurotoxic action has been postulated. In this work, we studied the effect
      of manganese administration on the neurochemical consequences of MPTP neurotoxic
      action. Male Swiss albino mice were treated with manganese chloride (MnCl2.4H2O;
      0.5 mg/ml or 1.0 mg/ml of drinking water) for 7 days, followed by three MPTP
      administrations (30 mg/kg, intraperitoneally). Seven days after the last MPTP
      administration, mice were sacrificed and dopamine and homovanillic acid contents
      in corpus striatum were analyzed. Striatal concentration of dopamine was found
      increased by 60% in mice pretreated with 0.5 mg/ml and 52% in the group treated
      of 1.0 mg/ml as compared versus animals treated with MPTP only. Homovanillic acid
      content in both groups treated with manganese was the same as those in control
      animals. The results indicate that manganese may interact with MPTP, producing an
      enhancement of striatal dopamine turnover, as the protective effect of manganese
      was more pronounced in the metabolite than in the neurotransmitter.

PMID- 8746810
TI  - Partial purification of a phosphoethanolamine methyltransferase from rat brain
      cytosol.
AB  - The conversion of phosphoethanolamine to phosphocholine requires 3 separate N
      methyltransferases. We had previously purified the enzyme catalyzing the last
      methylation, phosphodimethylethanolamine N-methyltransferase. We have
      successfully purified the enzyme catalyzing the initial methylation of
      phosphoethanolamine. A 434 fold purified enzyme from rat brain was obtained by
      the sequential use of ammonium sulfate fractionation, Q-Sepharose fast flow
      column chromatography and a omega-aminoethyl agarose column chromatography. The
      pH optimum was 11 or greater, the Km value for phosphoethanolamine was 167.8 +/-
      41.7 microM and the Vmax was 487.3 +/- 85 mmoles/mg/hr. The kinetics for S
      adenosyl-methionine, the methyldonor, has characteristics of cooperative binding
      with a Km of 1.805 +/- 0.59 mM and a Vmax of 16.9 +/- 3.6 mumoles/mg/hr. The
      activity was stimulated 6 fold by 2.5 mM MnCl2 and inhibited by DZA and S
      adenosylhomocysteine. These results reinforce the early in vivo observations
      which had provided suggestive evidence for the existence of a pathway for the
      methylation of phosphoethanolamine to phosphocholine in rat brain.

PMID- 8746809
TI  - Down-regulation of brain muscarinic cholinergic receptor promoted by
      diacylglycerols and phorbol ester.
AB  - Sustained agonist stimulation induces an asymmetric down-regulation of brain
      muscarinic acetylcholine receptor (mAChR): 43 +/- 2% in the right and 26 +/- 2%
      in the left cerebral hemisphere, respectively (Ref. 1). In order to determine the
      possible involvement of endogenous diacylglycerols produced under muscarinic
      stimulation in the down-regulation phenomenon, here we have studied the effects
      of synthetic diacylglycerols and a phorbol ester on cells dissociated from rat
      cerebral cortex. Oleylacetylglycerol decreased the amount of cell-surface mAChR
      by 37 +/- 2% and 25 +/- 2% in right and left cerebral cortex, respectively. Long
      term treatment with phorbol dibutyrate also produced internalization of the mAChR
      (25 +/- 1.5% and 33 +/- 2% in right and left cortical cells, respectively). These
      changes occurred without modification of the Kdapp for the selective antagonist
      pirenzepine. The action of calcium ions was also studied using incubation of
      cells with the ionophore A23187. No changes were observed in the amount of mAChR
      detected at the plasma membrane with the ionophore alone, but when used in
      combination with phorbol dibutyrate and the agonist carbamylcholine a sinergistic
      decrease in mAChR was apparent. It is concluded that long-term exposure to
      exogenously added diacyglycerols and phorbol ester significantly reduces the
      amount of mAChR detected at the plasma membrane and abolishes the asymmetry of
      the down-regulation phenomenon observed under specific muscarinic stimulation,
      suggesting that diacylglycerols may be one of the factors responsible for such
      asymmetry.

PMID- 8746811
TI  - Biosynthesis and compartmentalization of Po, apolipoprotein A-I, and lipids in
      the myelinating chick sciatic nerve.
AB  - Myelin deposition in developing chick sciatic nerve is associated with rapid
      synthesis of lipids, the major myelin protein Po and apo A-I, a major constituent
      of plasma lipoproteins. In order to understand possible roles of apo A-I in
      myelin assembly the synthesis and appearance of Po, apo A-I and lipids was
      studied in an intracellular fraction, an intralamellar fraction thought to be
      related to, or derived from, myelin and compact myelin from rapidly myelinating
      sciatic nerve of 1 day chicks. Incorporation with methionine or pulse-chase
      experiments indicated that initial synthesis of Po occurs in the intracellular
      fraction followed by movement to the intralamellar fraction and myelin.
      Incorporation of labelled oleate into phospholipids suggested that initial
      synthesis occurs in the intracellular and intralamellar fractions with slow
      movement to myelin. Incorporation of labelled galactose into cerebrosides
      suggested that initial synthesis occurs partially in myelin with slow loss from
      this fraction to the intralamellar fraction. However, incorporation of methionine
      into apo A-I indicated that initial synthesis occurred in the intracellular
      fraction with some transfer to the intralamellar fraction and secretion of a
      major portion into the incubation medium. It is concluded that the subcellular
      distribution of nascent apo A-I is not well coordinated with the distribution of
      other nascent constituents of the myelin membrane. The accumulation of nascent
      Po, phospholipids and cerebrosides in the intralamellar fraction compared to
      compact myelin suggests that this fraction may play a role as a precursor
      membrane or as a storage site for assembly of myelin constituents into compact
      myelin.

PMID- 8746812
TI  - Effect of thyroid deficiency on Go alpha-subunit isoforms in developing rat
      cerebral cortex.
AB  - Postnatal development of G alpha o isoforms in rat cerebral cortex was studied by
      SDS-PAGE and immunoblotting. When rat cerebral cortical membranes were resolved
      on separating gels containing 9% acrylamide and 8 M urea, three
      electrophoretically distinct G alpha o-immunoreactive proteins were evident.
      Comparison of their electrophoretic mobilities and partial tryptic digest pattern
      with recombinant G alpha o1 or G alpha o1-specific antibody revealed that the
      slowest and intermediate-migrating bands represent unmodified and fatty acylated
      forms of G alpha o1 protein, respectively. The fastest-migrating band corresponds
      to G alpha o2. While the fatty acylated form of G alpha o1 is the predominant
      species, its appearance paralleled that observed for G alpha o2 in developing rat
      cortex. Perinatal hypothyroidism induced by methimazole treatment did not
      significantly alter the appearance of cerebral cortical G alpha o1 and G alpha o2
      between days 1 and 22 postpartum. Our findings support the earlier idea that
      heterogeneity of G alpha o proteins in mammalian brain is likely the result of
      different co- or post-translational processings of each splice variant of G alpha
      o. While the appearance of G alpha o isoforms is developmentally regulated, they
      likely do not play an obligatory role in neonatal brain development.
      Alternatively, the expression of G alpha o isoforms in developing rat cortex may
      be controlled by an intrinsic signal(s) that is independent of the thyroid
      status.

PMID- 8746813
TI  - Evolution of classification systems for Graves' ophthalmopathy.
AB  - Numerous classification schemes for Graves' ophthalmopathy have been proposed in
      the past 50 years. The evolution of these systems, culminating in the consensus
      document created by the major international thyroid societies, is reviewed.

PMID- 8746814
TI  - Carotid-cavernous fistula mimicking Graves' eye disease.
AB  - We encountered two patients referred for treatment of Graves' eye disease who had
      atypical features and were found to have carotid-cavernous fistulae. The relevant
      clinical findings and investigations used to make this important distinction are
      described, and the factors involved in the initial diagnostic confusion are
      analyzed. A correct diagnosis leading to proper treatment was made once atypical
      features were taken note of and alternative diagnoses considered, despite the
      context of presumed Graves' eye disease. We conclude that these two entities are
      quite different but have enough similarities to overlap in certain clinical
      contexts.

PMID- 8746815
TI  - Orbital decompression for non-Graves' orbitopathy: a consideration of extended
      indications for decompression.
AB  - Orbital decompression is typically indicated for Graves' orbitopathy. Other
      causes of proptosis can also be safely and effectively addressed surgically with
      orbital decompression. Patients with prominent globes can have significant
      discomfort related to exposure keratopathy, lagophthalmos, and inefficient
      function of the globe-eyelid interface. We present six cases of non-Graves'
      proptosis that were addressed with orbital decompression. Indications for surgery
      included hypoplastic malar eminence with scleral show, enlarged globes, and
      congenital shallow orbits. Successful reduction of proptosis was achieved by
      orbital decompression with subsequent relief of presenting symptoms. Graded
      balanced orbital decompression was used to minimize shifts of the muscle cone. In
      some cases osteotomies and advancement of the lateral wall and malar region were
      also employed. Complications included transient esotropia, esotropia requiring
      surgery, and microplate granuloma. Orbital decompression should be considered for
      patients with relative proptosis and related eyelid malpositions regardless of
      the underlying etiology.

PMID- 8746816
TI  - Globe ptosis secondary to maxillary sinus mucocele.
AB  - Six patients were treated for gradual onset of enophthalmos, a deep superior
      sulcus and globe ptosis. There was no history of orbital trauma or sinusitis. CT
      scan showed an opacified shrunken maxillary sinus with dehiscence and depression
      of the orbital floor and downward displacement of the orbital contents.
      Pathological review of the surgical specimens showed a respiratory mucosal lining
      with thick mucoid secretions, new bone formation, but no purulence. The etiology
      is thought to be maxillary sinus mucocele. Surgical treatment with an
      otolaryngologist consisted of a Caldwell-Luc procedure to evacuate the maxillary
      sinus with nasal antrostomy and an orbital floor exploration with insertion of a
      methylmethacrylate implant molded at the time of surgery to reform the orbital
      floor and reposition the globe. Follow-up of 2 1/2-4 years shows excellent
      functional and cosmetic results.

PMID- 8746817
TI  - Surgical repair of the silent sinus syndrome.
AB  - Spontaneous enophthalamos and hypoglobus associated with the silent sinus
      syndrome are disfiguring for the patient and create functional problems, such as
      lagophthalmos and audible clicking while blinking. We describe a surgical
      technique that was used to successfully treat two patients with this disorder of
      maxillary sinus hypoplasia and orbital floor resorption. Two patients underwent
      transconjunctival exploration of the involved orbital floor with simultaneous
      Caldwell-Luc procedure. The floor was elevated by packing the maxillary sinus,
      and the remainder of the orbital soft-tissue volume disparity was filled with
      either autogenous nasal septal cartilage or banked irradiated costochondral
      cartilage. Both patients had uncomplicated, complete resolution of their
      functional problems and cosmetic disfigurement. These patients remained
      clinically stable for a 1-year follow-up period. This technique appears to be a
      safe and effective means to correct the functional and cosmetic abnormalities
      associated with the silent sinus syndrome.

PMID- 8746818
TI  - Endoscopy and biopsy of the orbit.
AB  - Flexible endoscopes produce high-quality images, are small in size, and can
      deliver microsurgical instruments or laser probes. Early attempts at orbital
      endoscopy were limited by the relatively large size and poor visualization of
      rigid endoscopes. We performed endoscopic orbital exploration using the Olympus
      HYF flexible endoscope in four live dog orbits. We achieved excellent
      visualization of orbital structures including the globe, blood vessels,
      extraocular muscles, intermuscular septa, optic nerve, and fat. Visualization,
      hemostasis, and dissection were aided by the use of hyaluronic acid infused
      through the endoscope. We biopsied fat and extraocular muscle without
      complication using Olympus endoscopic cup biopsy forceps (confirmed by
      histopathologic examination). Our experience indicates that orbital endoscopy
      aided by viscoelastic hydrodissection may permit a less invasive approach to
      optic nerve sheath fenestration, tumor biopsy and treatment, and the removal of
      foreign bodies.

PMID- 8746819
TI  - Histological and radiological analyses of hydroxyapatite orbital implants in
      rabbits.
AB  - To date, only anectodal clinical data exist pertaining to the histological
      changes of hydroxyapatite within an enucleated socket. This study was conducted
      to determine the histological and radiological changes in a coralline
      hydroxyapatite sphere placed into the central socket, in a controlled fashion.
      Rabbits underwent simple enucleation with implantation of an autologous sclera
      wrapped hydroxyapatite spheres with extraocular muscle reattachment.
      Preoperatively, the mineral density of each sphere was determined using
      quantitative computed tomography (CT) that was repeated 2- and 6 weeks
      postoperatively. The implants were harvested at 2- and 6 weeks and submitted for
      light and electron microscopic analysis. The results demonstrated a uniform
      influx of fibrovascular tissue that did not reach the center of the implant, even
      at 6 weeks. A marked mixed-cell inflammatory response was noted at the interface
      between the fibrovascular tissue and the hydroxyapatite. Giant cells were noted
      only at the scleral windows. This study demonstrated that the early response to
      hydroxyapatite implants was fibrovascular ingrowth with mixed-cell inflammation.
      These histological observations correlated with findings observed with
      quantitative CT. Quantitative CT appears to be an ideal modality for observing
      the early temporal tissue density changes in hydroxyapatite implants.

PMID- 8746821
TI  - Tarsal transposition flap to repair inner lamella defects.
AB  - We report the results of using a tarsal plate flap from the upper lid hinged at
      the lateral canthus to repair a lower lid inner lamella defect in 54 patients.
      Good functional and cosmetic results were achieved.

PMID- 8746820
TI  - Hemifacial atrophy: an unusual cause of upper eyelid retraction.
AB  - Progressive hemifacial atrophy or Parry Romberg syndrome may present with
      variable ocular features, the commonest being enophthalmos. We report a mild case
      in a 62-year-old man who presented with upper eyelid retraction, nocturnal
      lagophthalmos, and symptoms of corneal exposure. Recession of the levator muscle
      corrected the lid retraction and abolished the symptoms of corneal exposure.

PMID- 8746822
TI  - Congenital shortening of the anterior lamella of all eyelids: the so-called
      ablepharon macrostomia syndrome.
AB  - The so-called ablepharon macrostomia syndrome is an extremely rate congenital
      condition that includes abnormal ears, an enlarged, fishlike mouth, absence of
      lanugo, redundant skin, and vertical shortening of all eyelids. Only four cases
      have been described so far. In these cases the nature of the eyelid anomalies has
      not been clearly defined. We report one more case showing that the condition is
      better described as a severe microblepharon because only the anterior lamella of
      the eyelids is shortened. The literature about this condition is reviewed, and
      oculoplastic treatment is discussed.

PMID- 8746823
TI  - Colobomatous ocular cyst excision with globe preservation.
AB  - Colobomatous ocular cyst is a rare malformation consisting of a cavity lined by
      neuroectodermic tissue and communicating with the vitreous cavity, generally
      associated with microphthalmos. The usual treatment for unsightly cases is
      enucleation and cyst excision, followed by prosthesis fitting. The authors
      treated a case of colobomatous ocular cyst associated with a mild microphthalmos
      by cyst excision and pedicle ligature, via a transconjunctival orbitotomy. The
      postoperative appearance was satisfactory. Pathology confirmed a thick fibrous
      wall with calcifications, lymphocytic infiltrates, and neurofilaments and
      internally lined by dysplastic retinal elements. A conservative approach is
      advised for colobomatous cysts associated with a globe almost normally in size,
      in order to avoid cosmetic complications associated with enucleation in
      childhood.

PMID- 8746824
TI  - Congenital eversion of the upper eyelid: a case report.
AB  - Congenital ectropion of the upper lid is a rare condition that, if treated early,
      can be managed without recourse to surgery. We report a case in which an initial
      attempt at treatment with a pressure bandage failed, leading to a rapid worsening
      of the condition. A subsequent attempt at repositioning led to a respiratory
      arrest. Successful resolution occurred after taping of the lid. The case
      illustrates the need for early successful repositioning to break a cycle leading
      to increasing lid oedema; it also illustrates the importance of vigilance to the
      autonomic effects of lid manipulations in neonates.

PMID- 8746825
TI  - Oculoplastic surgery pearl. A procedure to decrease discomfort in blepharoptosis
      surgery.

PMID- 8746826
TI  - Discussion of "dermoid cysts: 16-year survey" by Bonavolanta et al.

PMID- 8746827
TI  - Management of loop retraction after silicone intubation.

PMID- 8746828
TI  - Direct transposition of the distal cervical vertebral artery into the internal
      carotid artery.
AB  - From January 1979 to December 1991, 92 revascularizations of the V3 segment of
      the vertebral artery were performed in 91 patients through a direct transposition
      of this artery into the internal carotid artery (ICA). These cases represented
      15.1% of 610 vertebral revascularizations and 38.8% of 280 distal vertebral
      revascularizations performed during this period at our institution. The sex ratio
      of this population was 0.59, and the mean age was 59.4 +/- 13.2 years (range 14
      to 82 years). Preoperative ischemic symptoms were vertebrobasilar in 87 (94.6%)
      cases, exclusively hemispheric in one (1.1%), and absent in the remaining four
      (4.3%). One of these four patients had asymptomatic severe multivessel occlusive
      disease and three others underwent resection of a spinal tumor involving the
      vertebral foraminal canal. In 31 (33.7%) cases significant carotid occlusive
      disease was also present. The distal V3 segment of the artery was directly
      transposed into the ICA in all cases in this series. In 24 (26.1%) cases the ICA
      was endarterectomized during the same operation. There were no deaths or strokes
      in this series but there were two (2.2%) transient ischemic attacks-one
      vertebrobasilar and the other hemispheric. However, eight (8.7%) transposed
      vertebral arteries were totally occluded at early follow-up. At 1 month, among
      the 87 patients with vertebrobasilar insufficiency, 44 (50.6%) were cured, 31
      (35.6%) were improved, and 12 (13.8%) remained unchanged. Among the 12 who were
      unchanged, eight (66.7%) had occlusion or stenosis of the distal transposition at
      the time of discharge. At 5 years, the primary patency rate in the series was
      89.1% +/- 7.2%. At the time of the last follow-up, among the 87 patients with
      vertebrobasilar insufficiency, 50 (57.5%) were cured, 25 (28.7%) were improved,
      two (2.3%) had remained unchanged since the operation, two (2.3%) suffered a
      relapse, and eight (9.2%) exhibited vertebrobasilar symptoms of varying severity
      and therefore could not be considered improved. Direct transposition of the V3
      segment of the vertebral artery into the ICA is a simple, safe, and reliable
      technique for revascularization of the distal cervical vertebral artery.

PMID- 8746829
TI  - Retroperitoneal approach for repair of inflammatory aortic aneurysms.
AB  - Inflammatory aortic aneurysms (IAAs) are characterized by a markedly thickened
      aortic wall and dense perianeurysmal fibrosis. The presence of such inflammation
      and subsequent organ adherence makes surgical repair of IAAs more challenging
      than repair of simple atherosclerotic aneurysms. From March 1987 to June 1994,
      twelve patients underwent surgical repair of an IAA by a single surgeon. Ten
      patients were men (83%) and the mean age was 68.3 years (range 58 to 93 years).
      All patients except one were symptomatic with back or abdominal pain, yet none
      had evidence of aneurysm rupture at operation. Preoperatively 90% (9/10) of the
      patients had an elevated erythrocyte sedimentation rate (ESR), 100% (12/12) had a
      predictive CT scan, and all patients with aortic wall pathology specimens had
      their diagnosis confirmed. Six patients had a left flank retroperitoneal surgical
      approach, five had a transabdominal approach, and one had ligation and extra
      anatomic reconstruction. The choice of repair technique was based on the degree
      and anatomic distribution of perianeurysmal fibrosis. The 30-day operative
      mortality rate was 0%. Mean follow-up was 56.3 months. Aortoduodenal fistula
      occurred in one patient 5 months after transperitoneal repair. Technical
      difficulties encountered during subsequent transperitoneal repairs led to the
      evolution of a policy in which the retroperitoneal approach was preferred in all
      patients with CT evidence of IAA. It is concluded that IAA represents a spectrum
      of retroperitoneal fibrosis and inflammation that is best treated surgically via
      a retroperitoneal approach.

PMID- 8746830
TI  - Ruptured abdominal aortic aneurysm: impact of comorbidity and postoperative
      complications on outcome.
AB  - Ruptured abdominal aortic aneurysm (AAA) remains a common and highly lethal
      problem. This study evaluates the morbidity and mortality rates and aims to
      identify which clinical variables could predict the outcome. We reviewed the
      records of 112 patients (97 men and 15 women) operated on for ruptured infrarenal
      AAA within the past 12 years (April 1, 1980, to March 31, 1992). Forty-seven
      clinical variables were collected and correlated with outcome by univariate and
      multivariate analysis. Mean age was 72.4 years (range 51 to 89 years). Only 12.5%
      were known to have an AAA before rupture. Preoperative systolic pressure < 90 mm
      Hg was present in 84 patients (75%) and 11 patients (9.8%) experienced cardiac
      arrest before surgery. The in-hospital mortality rate was 49.1% (55/112). Two
      preoperative variables were associated with increased mortality: systolic
      pressure < 90 mm Hg and cardiac arrest (p = 0.04 and p = 0.009, respectively).
      Preoperative comorbidity had no impact on outcome. Massive blood loss (> or =
      5000 ml) was an intraoperative factor predictive of increased mortality (p =
      0.0007). After multivariate analysis, only the following five postoperative
      variables were associated with increased mortality: cardiac event, renal failure
      requiring dialysis, coagulopathy, bleeding, and multisystem organ failure (all p
      < 0.05). We did not identify a preoperative factor that predicts certain death
      and allows us to deny a patient a chance at survival. The occurrence of
      multisystem organ failure is associated with no survivors and raises the ethical
      issue of withholding treatment for these patients in the postoperative course. We
      favor selective screening and aggressive elective repair to improve survival by
      operating before rupture occurs.

PMID- 8746831
TI  - Fibrinolysis profiles and platelet activation after endothelial cell seeding of
      prosthetic vascular grafts.
AB  - There is no convincing evidence that endothelial cell seeding of prosthetic
      grafts in humans confers any of the advantages seen in animals. However, partial
      endothelial coverage might exert a subtle effect not detectable with indirect end
      points such as patency or scintigraphy. This study examined seeded cell function
      by measuring fibrinolytic and platelet activation markers in patients receiving
      seeded and control prosthetic grafts. Thirty-two patients were randomly assigned
      to seeded (n = 15) and control (n = 17) groups. Preoperatively and 3, 6, and 12
      months postoperatively, plasma levels of fibrinopeptide A (FPA), B beta 1-42
      fragment, cross-linked fibrin degradation products (XL-FDP), thromboxane A2
      (TXA2), platelet factor 4 (PF4), and beta-thromboglobulin (beta TG) were
      measured. Patients with seeded grafts had significantly lower levels of FPA at 6
      and 12 months (p < 0.05) and a significant overall group effect (p < 0.05). These
      patients also tended to have higher levels of XL-FDP (p < 0.1). No other
      significant differences were seen. The lower rate of conversion of fibrinogen to
      fibrin and the trend toward increased fibrinolysis seen in seeded grafts may be
      due to the metabolic effects of viable retained seeded cells. Although comparable
      platelet activation indicates that endothelial coverage remains limited, seeding
      may exert an antithrombotic influence at the graft surface.

PMID- 8746832
TI  - Long-term surveillance by duplex scanning of nonrevised infragenicular graft
      stenosis.
AB  - To define the prognosis of nonrevised graft stenosis, we studied 68
      infragenicular bypass grafts in patients entered into our duplex surveillance
      program between 1986 and 1987. Patients were grouped according to the grade of
      stenosis as follows: grade I = < 50% stenosis, grade II = 50% to 75% stenosis,
      and grade III = 75% to 99% stenosis. Time until maximum stenosis was stratified
      into three intervals (< 3 months, between 3 and 12 months, and > 12 months).
      Cumulative patency rates from the time of maximum stenosis to failure were
      calculated using Kaplan-Meier analysis. Fifty-three grafts (78%) developed
      stenoses: 10 with grade I, 25 with grade II, and 18 with grade III stenosis.
      Eighty-nine percent of the 18 graft occlusions occurred within 2 years. Two
      grafts occluded after 2 years without any severe stenosis or preceding clinical
      signs. During follow-up 15 nonrevised stenosed grafts (four with grade I, five
      with grade II, and six with grade III stenosis) remained patent longer than 2
      years with a mean follow-up of 72 months. Statistical analysis for graft failure
      determined that grade II to III stenoses led to graft occlusion significantly
      earlier than grade 0 to I stenoses (p = 0.017). If graft failures resulting from
      revision were separated from the analysis, the time interval from operation to
      maximum stenosis (within 1 year) remained marginally significant for predicting
      occlusion, whereas no correlation was found between the grade of maximum stenosis
      and occlusion. Thus the prognosis for graft stenosis depends on the grade of
      stenosis and on the time interval from operation to stenosis. Therefore duplex
      surveillance seems to be most important within the first 24 months only, but is
      of little use in predicting impending graft failure beyond 2 years in
      asymptomatic patients.

PMID- 8746833
TI  - The relationship between arm-ankle pressure difference and peak systolic velocity
      in patients with stenotic lower extremity vein grafts.
AB  - The relationship between the measured arm-ankle pressure difference (AAPD), or
      the ankle/arm index (AAI), and the focal peak systolic velocity (PSV) at stenotic
      sites of infrainguinal vein grafts has not been determined. We attempted to
      relate these two parameters. We used Doppler systolic pressures and duplex
      ultrasonography to study 35 infrainguinal vein bypass grafts followed in a
      surveillance protocol. The following graft groups were identified: grafts in
      nondiabetic patients (n = 26), grafts in diabetic patients (n = 9), nonrevised
      stenotic grafts (n = 14), revised stenotic grafts (n = 14), and normal grafts (n
      = 7). AAPD and AAI were measured in both lower extremities. Pressure gradients
      across graft stenoses were indirectly estimated using the modified Bernoulli
      equation (delta P =4V2). Measured AAPDs and estimated pressure gradients showed
      moderate correlation in nondiabetic (r = 0.58) and diabetic (r = 0.63) patients.
      Correlation was fair (r = 0.3) prior to graft revision. There was no correlation
      (r = 0.1) in the nonrevised stenotic grafts. For individual patients with
      stenotic grafts who were followed in consecutive visits, the correlation varied
      from none to good (r range 0.01 to 0.71). We conclude that there is a lack of
      consistent correlation between the measured AAPD, or AAI, and the estimated
      stenotic graft pressure gradient. This finding illustrates the limitation of the
      AAI as a monitoring test to predict failure of stenotic infrainguinal vein
      grafts.

PMID- 8746834
TI  - Blue toe syndrome from a "coral reef" aorta.
AB  - An endoaortic calcified mass, sometimes referred to as a "coral reef" aorta, is
      an unusual cause of distal leg microembolization. When discovered it is usually
      in the suprarenal aorta. We present an unusual case of infrarenal coral reef
      aorta with symptoms of distal atheroembolism. A review of the literature is also
      presented.

PMID- 8746835
TI  - Budd-Chiari syndrome secondary to carcinoma: report of two cases.
AB  - In two patients who had Budd-Chiari syndrome secondary to carcinoma, the
      diagnosis was made intraoperatively at the time of emergency right atrial
      clearance required for severe cardiovascular distress. Curative resection was not
      possible and both patients died. As previously noted in the literature, it is
      extremely difficult to relate carcinoma to the origin of Budd-Chiari syndrome.
      Retro- and suprahepatic involvement of the vena cava is associated with a very
      poor prognosis. Complete resection of these tumors is the only potentially
      curative treatment. We suggest ways to obtain a simple and early histologic
      diagnosis before initiating appropriate and radical surgical treatment.

PMID- 8746836
TI  - Proximal migration of vena caval filters: report of two cases with operative
      retrieval.
AB  - Operative retrieval of two proximally migrated vena caval filters was performed
      in two patients, ages 42 and 45 years, respectively. In the first patient the
      filter was encrusted in the right ventricle, and in the second one the filter was
      found in the pulmonary artery. Both filters were retrieved under cardiopulmonary
      bypass via an incision in the right atrium and the pulmonary artery,
      respectively. These two observations underscore the risk of increased unwarranted
      indications and consequent higher complication rates of vena caval filters.

PMID- 8746837
TI  - Vascular holism: the epidemiology of vascular disease.
AB  - This article reviews the distinguishing features of epidemiology and clinical
      medicine and their interdependence in clinical epidemiology as applied to
      vascular disease. Selected literature is reviewed to emphasize the principles of
      clinical epidemiology for five vascular disorders: abdominal aortic aneurysms,
      lower extremity peripheral arterial occlusive disease, cerebrovascular disease,
      deep vein thrombosis and pulmonary embolism, and varicose veins. These vascular
      disorders are prevalent and pose significant risks for death and disability. Many
      have risk factors that can be controlled. All can be treated by vascular surgery,
      but outcomes including functional health and well-being may fall short of that
      which is implied in our traditional surgical literature. Appropriate allocation
      of resources to detect and treat vascular disease demands that clinicians not
      only assume responsibility for the care of individual patients but also develop a
      working knowledge of the clinical epidemiology of vascular health and disease and
      its management within populations.

PMID- 8746838
TI  - Sequential distal anastomosis in aortofemoral bypass.

PMID- 8746839
TI  - Technique of thoracoabdominal aneurysm repair.

PMID- 8746840
TI  - Dissecting descending thoracic and thoracoabdominal aortic aneurysms: Part II.

PMID- 8746841
TI  - Transperitoneal medial visceral rotation.

PMID- 8746842
TI  - Experimental determination of control by the H(+)-ATPase in Escherichia coli.
AB  - Strains carrying deletions in the atp genes, encoding the H(+)-ATPase, were
      unable to grow on nonfermentable substrates such as succinate, whereas with
      glucose as the substrate the growth rate of an atp deletion mutant was
      surprisingly high (some 75-80% of wild-type growth rate). The rate of glucose and
      oxygen consumption of these mutants was increased compared to the wild-type
      rates. In order to analyze the importance of the H(+)-ATPase at its physiological
      level, the cellular concentration of H(+)-ATPase was modulated around the wild
      type level, using genetically manipulated strains. The control coefficient by the
      H(+)-ATPase with respect to growth rate and catabolic fluxes was measured.
      Control on growth rate was absent at the wild-type concentration of H(+)-ATPase,
      independent of whether the substrate for growth was glucose or succinate. Control
      by the H(+)-ATPase on the catabolic fluxes, including respiration, was negative
      at the wild-type H(+)-ATPase level. Moreover, the turnover number of the
      individual H(+)-ATPase enzymes increased as the H(+)-ATPase concentration was
      lowered. The negative control by the H(+)-ATPase on catabolism may thus be
      involved in a homeostatic control of ATP synthesis and, to some extent, explain
      the zero control by the H(+)-ATPase on E. coli growth rate.

PMID- 8746843
TI  - Skeletal muscle: a paradigm for testing principles of bioenergetics.
AB  - Muscular activity converts chemical energy into useful work and metabolism
      restores muscle to its original state. This essay explores the organization and
      interactions of the regulatory system(s) which allow this energy balance to
      occur. The term "energy balance" is used in a biochemical rather than a
      thermodynamic sense--concerned not with deductions from the physical principles
      of thermodynamics, but rather with those enzymatic processes which nature evolved
      and which operate at remarkably fixed stoichiometry. Energy balance is a
      statement of conservation of energy put into biochemical observables. 31P NMR
      spectroscopy is one of the most useful techniques for investigating these
      questions quantitatively under physiological conditions in vivo. The author (1)
      describes the rules or principles of biochemical energy balance; (2) discusses
      sample results from human muscle to demonstrate its use in studying this class of
      questions; (3) presents a simple model of integrated cellular respiration to
      demonstrate its sufficiency to account for the main observations.

PMID- 8746844
TI  - Regulation of energy metabolism in liver.
AB  - Energy metabolism in liver has to cope with the special tasks of this organ in
      intermediary metabolism. Main ATP-generating processes in the liver cell are the
      respiratory chain and glycolysis, whereas main ATP-consuming processes are
      gluconeogenesis, urea synthesis, protein synthesis, ATPases and mitochondrial
      proton leak. Mitochondrial respiratory chain in the intact liver cell is subject
      to control mainly by substrate (hydrogen donors, ADP, oxygen) transport and
      supply and proton leak/slip. Whereas hormonal control is mainly on substrate
      supply to mitochondria, proton leak/slip is supposed to play an important role in
      the modulation of the efficiency of oxidative phosphorylation.

PMID- 8746846
TI  - Extracellular ascorbate stabilization as a result of transplasma electron
      transfer in Saccharomyces cerevisiae.
AB  - The presence of yeast cells in the incubation medium prevents the oxidation of
      ascrobate catalyzed by copper ions. Ethanol increases ascorbate retention.
      Pyrazole, an alcohol dehydrogenase inhibitor, prevents ascorbate stabilization by
      cells. Chelation of copper ions does not account for stabilization, since
      oxidation rates with broken or boiled cells or conditioned media are similar to
      control rates in the absence of cells. Protoplast integrity is needed to reach
      optimal values of stabilization. Chloroquine, a known inhibitor of plasma
      membrane redox systems, inhibits the ascorbate stabilization, the inhibition
      being partially reversed by coenzyme Q6. Chloroquine does not inhibit
      ferricyanide reduction. Growth of yeast in iron-deficient media to increase
      ferric ion reductase activity also increases the stabilization. In conclusion,
      extracellular ascorbate stabilization by yeast cells can reflect a coenzyme Q
      dependent transplasmalemma electron transfer which uses NADH as electron donor.
      Iron deficiency increases the ascorbate stabilization but the transmembrane
      ferricyanide reduction system can act independently of ascorbate stabilization.

PMID- 8746845
TI  - Control of mitochondrial and cellular respiration by oxygen.
AB  - Control and regulation of mitochondrial and cellular respiration by oxygen is
      discussed with three aims: (1) A review of intracellular oxygen levels and
      gradients, particularly in heart, emphasizes the dominance of extracellular
      oxygen gradients. Intracellular oxygen pressure, pO2, is low, typically one to
      two orders of magnitude below incubation conditions used routinely for the study
      of respiratory control in isolated mitochondria. The pO2 range of respiratory
      control by oxygen overlaps with cellular oxygen profiles, indicating the
      significance of pO2 in actual metabolic regulation. (2) A methodologically
      detailed discussion of high-resolution respirometry is necessary for the
      controversial topic of respiratory control by oxygen, since the risk of
      methodological artefact is closely connected with far-reaching theoretical
      implications. Instrumental and analytical errors may mask effects of energetic
      state and partially explain the divergent views on the regulatory role of
      intracellular pO2. Oxygen pressure for half-maximum respiration, p50, in isolated
      mitochondria at state 4 was 0.025 kPa (0.2 Torr; 0.3 microM O2), whereas p50 in
      endothelial cells was 0.06-0.08 kPa (0.5 Torr). (3) A model derived from the
      thermodynamics of irreversible processes was developed which quantitatively
      accounts for near-hyperbolic flux/pO2 relations in isolated mitochondria. The
      apparent p50 is a function of redox potential and protonmotive force. The
      protonmotive force collapses after uncoupling and consequently causes a decrease
      in p50. Whereas it is becoming accepted that flux control is shared by several
      enzymes, insufficient attention is paid to the notion of complementary kinetic
      and thermodynamic flux control mechanisms.

PMID- 8746848
TI  - International disease surveillance: July to September 1995.

PMID- 8746847
TI  - Ehrlich cell plasma membrane redox system is modulated through signal
      transduction pathways involving cGMP and Ca2+ as second messengers.
AB  - Ehrlich cell plasma membrane ferricyanide reductase activity increased in the
      presence of mastoparan, a generic activator of G proteins, using either whole
      cells or isolated plasma membrane-fractions. Agents that increase intracellular
      cAMP also increased the rate of ferricyanide reduction by Ehrlich cells. For the
      first time, evidence is shown on a modulation of plasma membrane redox system by
      cGMP. In fact, permeant analogs of cGMP, dibutyryl cGMP, and 8-bromo-cGMP
      increased the rate of ferricyanide reduction by the Ehrlich cell plasma membrane
      redox system. Furthermore, specific inhibition of cGMP-phosphodiesterases by
      dipyridamole was also accompanied by an enhancement in the rate of ferricyanide
      reduction. On the other hand, treatments expected to increase cytoplasmic Ca2+
      concentrations were accompanied by a remarkable stimulation of the reductase
      activity. Taking all these data together, it seems that the Ehrlich cell plasma
      membrane redox system is under a multiple and complex regulation by different
      signal transduction pathways involving G proteins, cyclic nucleotides, and Ca2+
      ions.

PMID- 8746849
TI  - Inactivation of the bovine spongiform encephalopathy agent by rendering
      procedures.
AB  - Bovine brain infected with the bovine spongiform encephalopathy (BSE) agent was
      used to spike material processed in pilot scale facsimiles of 12 rendering
      processes which are used within the European Union, and three which are not. The
      raw materials for experimental rendering represented those used in practice, and
      consisted of appropriate proportions of BSE-infected brain tissue, bovine or
      porcine intestine, and bovine bone. Meat and bone meal, and tallow were produced
      from the rendered tissues. Suspensions of all the meat and bone meal samples were
      assayed in inbred mice for BSE infectivity, and two of the tallow fractions were
      tested similarly. Four of the 15 processes produced meat and bone meal with
      detectable BSE infectivity. Neither of the tallow samples had detectable
      infectivity.

PMID- 8746850
TI  - Diagnosis of bovine fetal Neospora infection with an indirect fluorescent
      antibody test.
AB  - Fetal fluids from 138 spontaneously aborted bovine fetuses were examined for the
      presence of antibodies against Neospora antigens by means of an indirect
      fluorescent antibody test (IFAT). The fetuses were divided into group 1,
      consisting of 74 fetuses with confirmed or presumptive fetal neosporosis, and
      group 2, consisting of 64 fetuses with either no aetiological diagnosis,
      presumptive diagnoses of non-Neospora infections or non-infectious diseases, or
      fetuses with confirmed diagnoses of other fetal diseases. Thirty-seven of the 74
      fetuses in group 1 had detectable titres of antibody to Neospora; approximately
      21 per cent of the fetuses between three and five months gestation, 56 per cent
      of these between six and seven months gestation, and 93 per cent of these between
      eight and nine months gestation, had detectable titres of antibody. Only one of
      the 64 fetuses in group 2 had a detectable titre of antibody to Neospora.

PMID- 8746851
TI  - An unusual case of distal phalanx fracture in a horse.
AB  - A mature thoroughbred cross gelding with an acute onset forelimb lameness was
      found to have sustained a fracture to the distal phalanx. The fracture traversed
      the distal phalanx In a lateromedial direction dividing the phalanx into two
      halves, dorsally and palmarly and was classed a frontal fracture. The horse was
      treated conservatively and after 14 months rest it returned to work. Three years
      later the horse has remained sound.

PMID- 8746852
TI  - Nervous mortality syndrome in farmed Atlantic salmon.

PMID- 8746853
TI  - Effect of doramectin on the performance of cattle exposed to gastrointestinal
      worms and lungworms in Ireland.

PMID- 8746854
TI  - Desflurane in equine anaesthesia: a preliminary trial.

PMID- 8746855
TI  - Availability of medicines for poultry produced for meat.

PMID- 8746856
TI  - Rabies control in the developing world.

PMID- 8746857
TI  - Circovirus in pigeons.

PMID- 8746858
TI  - F17 positive Escherichia coli.

PMID- 8746859
TI  - Potential risk of effects of antimicrobial residues on human gastrointestinal
      microflora.

PMID- 8746860
TI  - Social differentials in chronic disease: what can sociological knowledge offer to
      explain and possibly reduce them?

PMID- 8746861
TI  - Medical humanitarianism and human rights: reflections on doctors without borders
      and doctors of the world.

PMID- 8746862
TI  - The implementation of health promotion: a new structural perspective.
AB  - Although health promotion has become a critical concept in public health, both
      research and practical projects in this area are almost devoid of theory. The
      present article uses a theory of complexity and structure to organize the
      different elements of health promotion in a new perspective. This perspective
      involves (1) new ways for looking at patterns of behavioral risk factors and
      health-related lifestyles. It (2) relates health promotion to policy making. In
      particular, it (3) focuses on a comprehensive model of the implementation
      process, revealing the true interrelationship of relevant elements to the concept
      of health promotion. In this context, it (4) becomes obvious that the reflexivity
      and recursiveness of scientific analyses are an integral part of the structure of
      health promotion. Thus, the professional role of the social scientist with
      regards to the implementation and utilization of scientific knowledge in the
      field of public health policy will be discussed. Finally, the role of appropriate
      theory is emphasized as a strategy for improving the practice of health promotion
      and to further the development of a new public health.

PMID- 8746864
TI  - Parental perceptions and attitudes about informed consent in clinical research
      involving children.
AB  - We interviewed 64 parents by questionnaire after completion of a clinical trial
      involving their children for their perceptions and attitudes about informed
      consent. The results show that only a small minority realized that drug trials
      are designed to assess not only efficacy but safety as well. More worrisome was
      the majority of parents who felt that drug trials conducted by hospitals are of
      no or low risks. Moreover, a significant minority offered the view that the
      strict informed consent procedures we followed were unnecessary because they
      would do what the doctor advised. Even more worrisome was the small percentage of
      parents who realized that a signed consent form was primarily meant to protect
      their rights, and only one-third of the parents knew of their right to withdraw
      their child unconditionally from the trial at any time. These findings suggest
      that there may be significant attitudinal barriers to parental understanding of
      the informed consent process.

PMID- 8746863
TI  - Correlates of health care satisfaction in inner-city patients with hypertension
      and chronic renal insufficiency.
AB  - Barriers to effective health care are potential contributors to the increased
      prevalence of hypertension and hypertension-related renal disease observed in
      black patients. We have enrolled 333 primarily elderly (mean age 69 years) black
      (87%) patients with hypertension and chronic renal insufficiency into a
      prospective randomized trial testing the effect of intense multidisciplinary
      management on progression of chronic renal insufficiency. These patients have an
      average 6 years of education and $400-$800 monthly household income: 57% have
      diabetes. Our baseline data include the Patient Satisfaction Questionnaire
      administered by home interviewers who also recorded sociodemographic data,
      medications and questionnaires regarding medication compliance and symptoms
      related to anti-hypertensive drugs. Inpatient and outpatient vital signs, test
      results and diagnoses came from patients' computerized medical records. We used
      multiple linear regression to identify correlates of overall satisfaction. We
      also analyzed three subscales: access to care, financial aspects and
      interpersonal manner of physicians. We included only variables with univariate
      correlations (P < 0.05) in the models. Decreased overall satisfaction correlated
      with more symptoms related to anti-hypertensive drugs (P < 0.001), lower
      medication compliance (P = 0.01), and higher diastolic blood pressure (P = 0.08).
      Decreased satisfaction with access to care correlated with more symptoms related
      to anti-hypertensive drugs (P < 0.001) and decreased medication compliance (P =
      0.08). Decreased satisfaction with financial aspects of care correlated with more
      symptoms related to anti-hypertensive drugs (P < 0.001), lower medication
      compliance (P = 0.01) and more proteinuria (P = 0.02). Finally, decreased
      satisfaction with interpersonal manner of physicians correlated with lower
      medication compliance (P < 0.001), lower albumin (P = 0.01) and sodium (P =
      0.04), and higher diastolic blood pressure (P = 0.04). These cross-sectional
      baseline data describe a group of mostly black inner-city patients with
      hypertension and chronic renal insufficiency in whom decreased satisfaction with
      care correlates with decreased medication compliance, increased symptoms related
      to anti-hypertensive drug therapy, higher diastolic blood pressure and more
      proteinuria. Our prospective study may help determine whether improving
      satisfaction improves compliance and blood pressure control, and forestalls
      complications in this high-risk population.

PMID- 8746865
TI  - Research and the health services manager in the developing world.
AB  - Recent work such as that of the Joint Health Systems Research Project has done a
      great deal to support and encourage health systems research. Despite that, health
      service managers in developing countries only rarely regard research as integral
      to the process of priority setting, planning and management. To some extent, this
      is because the organisational environment is not supportive of managerial
      initiatives for research-based change. Furthermore, health-related research tends
      to support a relatively narrow range of managerial activity. The research process
      itself militates against those qualitative research methods which would
      frequently provide the appropriate tools for the study of management problems.
      Six possible reasons for this are proposed. The first is the expectation of those
      controlling funding and research, that it should produce generalisations. Second,
      there is a gap between the biomedical research which tends to get funded, and the
      problems managers really need to solve. Third, disproportionate attention is
      given to the evaluation of health status over and above organisational states.
      Fourth, much health systems research tends to embody a simplistic assumption that
      the only social function of health services is to improve health. Fifth, much of
      the research which is done is evaluative, and evaluations are frequently required
      to tell us whether formal goals have been achieved; this both rules out a
      learning process approach, and militates against finding out what is actually
      happening. Sixth, the question is raised that funding agencies may play a major
      role in limiting the use of qualitative research methods. It is suggested that
      any such effect may be peculiar to the health sector. As a way ahead, conscious
      efforts to increase the extent to which the research environment helps managers
      to develop a problem-solving approach, are needed.

PMID- 8746866
TI  - What is participatory research?
AB  - Research strategies which emphasize participation are increasingly used in health
      research. Breaking the linear mould of conventional research, participatory
      research focuses on a process of sequential reflection and action, carried out
      with and by local people rather than on them. Local knowledge and perspectives
      are not only acknowledged but form the basis for research and planning. Many of
      the methods used in participatory research are drawn from mainstream disciplines
      and conventional research itself involves varying degrees of participation. The
      key difference between participatory and conventional methodologies lies in the
      location of power in the research process. We review some of the participatory
      methodologies which are currently being popularized in health research, focusing
      on the issue of control over the research process. Participatory research raises
      personal, professional and political challenges which go beyond the bounds of the
      production of information. Problematizing "participation', we explore the
      challenges and dilemmas of participatory practice.

PMID- 8746867
TI  - Ethnographic studies of ARI in Bolivia and their use by the national ARI
      programme.
AB  - Acute respiratory infections (ARI) are responsible for one quarter to one third
      of all deaths in infants and young children, with most deaths being attributed to
      pneumonia. At present, few measures exist to prevent pneumonia. However, most
      pneumonia deaths can be averted by treatment with an appropriate antibiotic. The
      effectiveness of this strategy depends on families' ability to recognize the
      signs of pneumonia, and to promptly seek care from a trained health practitioner.
      In order for health workers to communicate effectively with families about how to
      care for children with ARI, what signs to watch for, and when to come back for
      care, they need to know how families perceive and respond to respiratory
      infections. The WHO ARI Programme has recently developed a research protocol for
      conducting ethnographic studies of community perceptions and practices related to
      ARI. The purpose of this protocol is describe communities' explanatory models for
      ARI, identify cultural and other factors that facilitate or constrain appropriate
      home care and careseeking for children with ARI, and make recommendations to
      national ARI programmes about how to develop effective communication activities.
      This paper reports on two studies conducted in Bolivia using the WHO/ARI Focused
      Ethnographic Study (FES) protocol, and describes the way in which the data were
      utilized by the national ARI programme.

PMID- 8746868
TI  - Perception and social consequences of tuberculosis: a focus group study of
      tuberculosis patients in Sialkot, Pakistan.
AB  - Treatment defaulting is one of the major causes of the failure of TB control
      programs. In Bethania Hospital, Sialkot, defaulting rates are high: 72% for the
      standard 12 months course and 56% for the 8 months course. Attrition is
      especially important in the first weeks of treatment: < 70% of the patients start
      the 10th week of treatment. A focus group discussion study has been carried out
      to gain a better understanding of the impact of social stigmatization, treatment
      cost and pregnancy on defaulting. The study population consisted of 3 male and 3
      female groups each with 8 hospitalized TB patients. The study shows that TB is
      perceived as a very dangerous, infectious and incurable disease. This perception
      has many social consequences: stigmatization and social isolation of TB patients
      and their families: diminished marriage prospects for young TB patients, and even
      for their family members: TB in one of the partners may lead to divorce. Due to
      fear patients often deny the diagnosis and reject the treatment. While both male
      and female TB patients face many social and economical problems, female patients
      are more affected. Divorce and broken engagements seem to occur more often in
      female patients. Females are usually economically dependent on their husbands and
      family in law, and need their cooperation to avail of treatment. The belief that
      pregnancy enhances the risk for relapse decreases their marriage prospects.
      Pregnancy is also a reason for stopping TB treatment as both are considered as
      incompatible. The findings of this study reveal the urgent need for a health
      education campaign to convince the general population that tuberculosis is
      curable. All health care providers should act as destigmatizers.

PMID- 8746869
TI  - Child sexual abuse in Matabeleland, Zimbabwe.
AB  - The extent, nature, causes and consequences of child sexual abuse in
      Matabeleland. Zimbabwe, are explored by an intersectoral working group consisting
      of health, legal and AIDS prevention workers who were struck in the course of
      their work by the regularity with which they saw sexually abused children
      infected with HIV and STDs. Methods used in this study are record review, focus
      group discussions, structured and in-depth interviews. Child sexual abuse cases
      form between 40-60% of the rape cases brought to the attention of hospitals,
      police and court and many more are believed to remain unreported. Half of the
      sexual abuse in children is detected through STDs and some have HIV. The majority
      of offenders are mature men known to the child. Factors influencing child sexual
      abuse are male dominance in society, men's professed inability to control sexual
      desire, and magic beliefs. Victims are traumatized by the abuse itself as well as
      by subsequent problems in family, health and in court. Since child sexual abuse
      may endanger the life and well-being of the child, it is a serious problem that
      requires urgent action.

PMID- 8746870
TI  - Socio-cultural and behavioural aspects of mosquito-borne lymphatic filariasis in
      Thailand: a qualitative analysis.
AB  - This study examines the contribution of socio-cultural and behavioural factors in
      mosquito-borne lymphatic filariasis transmission in Southern Thailand. Research
      was conducted in Nakorn-srithamarat province, which is noted for having the
      nation's highest Brugia malayi filariasis morbidity rate. Factors examined
      include traditional knowledge and cultural beliefs concerning etiology,
      transmission and symptomatology; perceived susceptibility and severity: social
      stigma: social support in disease prevention and control; and behavioural risk
      factors and illness behaviours. Data were collected through a multi-method,
      predominantly qualitative-based approach, including rapid survey and mapping,
      group interviews, focus group discussions, indepth interviews, and participant
      observation. Results indicate that poor knowledge and lay, indigenous,
      traditional belief systems contribute to high risk behaviours, and inappropriate
      preventive, illness and treatment choice behaviours. Behavioural models for
      explaining filariasis risk, preventive, illness and treatment choice behaviours
      are presented. Finally, recommendations for more effective health education
      programmes are offered.

PMID- 8746871
TI  - Learning to listen: formative research in the development of AIDS education for
      secondary school students.
AB  - AIDS, as a social phenomenon, is highly politicized and is an emotive issue. In
      South Africa there is considerable disagreement between different sectors and
      stakeholders involved in school education about what constitutes an appropriate
      approach to AIDS education. For AIDS education programmes in schools to make
      cultural sense and to be effective, adequate formative research of the social
      context and cultural meaning of the salient behaviours needs to be done, and this
      understanding needs to inform programme development. The school community needs
      to be involved in the programme design and evaluation. This paper describes some
      of the formative research undertaken during the development of an AIDS education
      programme for secondary school students in South Africa. The study was undertaken
      during 1991 and 1992 in a Cape Town secondary school. A description of three
      components of the formative research is given. For each, the qualitative research
      methods used, the difficulties encountered, some of the results, and their value
      are discussed. Qualitative research methods were able to provide a more holistic
      understanding of student sexuality and its cultural context. These methods also
      provided the means with which to develop a partnership with the teachers in the
      process of developing the AIDS education programme. Furthermore, when this
      partnership broke down, they provided the means to explore the crisis that
      emerged around conflicting assumptions and cultural values the researchers and
      the "researched' held with respect to AIDS education. The generalizability of the
      study's results and the transferability of the AIDS education programme that was
      developed are discussed with respect to the exigencies of epidemiology to impact
      on the public health of large populations, and those of qualitative research
      methods to generate in-depth understanding in limited contexts.

PMID- 8746872
TI  - How do health service managers respond to qualitative research?
AB  - During 1992 a qualitative evaluation of a government health service-run community
      health worker (CHW) project in South Africa found that project workers were doing
      good work despite serious structural shortcomings related to lack of community
      participation and inadequate integration of the project in the health district
      system. Recommendations were made to develop the project in order to enhance
      community involvement, to build closer integration between the project and the
      services offered at the health centre, and to collaborate with non-government CHW
      projects in neighbouring areas. The evaluation study was followed up one year
      later by interviews with health managers to determine their response to the
      evaluation. The managers reported that they had found the qualitative data
      valuable for understanding how clients perceived the health service, and for
      planning a more community-responsive service. Despite this, the recommendations
      from the evaluation were not implemented and political developments in the
      district resulted in the CHW project being closed down. It is concluded that
      qualitative evaluators need to carefully explore the political context of primary
      health care interventions in order that their research provides useful data for
      decision-making.

PMID- 8746873
TI  - Phytoestrogens--a short review.
AB  - The wide distribution of plant estrogens or 'phytoestrogens' in cereals,
      vegetables and medicinal plants raises questions concerning the possible health
      risks and benefits associated with their consumption. In this article, we provide
      a synopsis of the literature relating principally to the clinical effects of
      phytoestrogens on the diseases associated with ageing. The sources, metabolism
      and properties of the different phytoestrogens are also discussed. The studies
      included were primarily restricted to those with data pertinent to clinical
      practice. Our contention is that phytoestrogens are at least part of the reason
      why vegetarians and Asian populations have a low rate of cancer and heart
      disease.

PMID- 8746874
TI  - Women's anticipations of hormonal replacement therapy.
AB  - Middle class Caucasian women's anticipations about hormonal replacement therapy
      (HRT) for perimenopausal symptoms were investigated to expand an understanding of
      elective use of HRT. This focused ethnography used both interviews and
      participation in discussion groups established for perimenopausal women as
      sources of data. Two investigators augmented validity. Inductive and deductive
      analysis yielded six typologies of anticipations: trusting in nature, fixing,
      skeptical experimenting, restabilizing, life enhancing, and trusting in science.
      These findings have clinical and theoretical implications related to issues of
      non-compliance, health seeking behaviour, provider-recipient interaction, and the
      focus of scientific investigation.

PMID- 8746875
TI  - The chronological change of vertebral bone loss following oophorectomy using dual
      energy X-ray absorptiometry: the correlation with specific markers of bone
      metabolism.
AB  - The changes of vertebral bone mineral density (BMD; g/cm2) following oophorectomy
      were studied, using dual energy X-ray absorptiometry (DEXA) in 38 premenopausal
      and 244 oophorectomized women. Two biochemical indices of bone remodeling,
      urinary deoxypyridinoline (DPyr) for bone resorption and serum intact human
      osteocalcin (hOC) for bone formation, were also measured at the same time. The
      rate of bone loss in the first year after oophorectomy was 10.7%, while that in
      the second year was 5.7% (rapid phase), followed by a slow phase at the rate of
      1.1%. The bone mass finally reached an osteoporotic level (BMD < 0.767 g/cm2) at
      12 years after oophorectomy. The DPyr increased to reach a peak level in the
      first year, whereas the hOC increased and reached its peak level in the second
      year after surgery. The maximal bone loss in the first year is considered to be
      caused by the remarkable increase of bone resorption and the biological delay of
      the maximal increase in bone formation.

PMID- 8746876
TI  - Perimenopausal changes in serum lipids and lipoproteins: a 7-year longitudinal
      study.
AB  - Although cross-sectional studies suggest considerable influence of menopause on
      serum lipids and lipoproteins in women, it is not exactly clear. During our 7
      year longitudinal study, serum concentrations of total cholesterol, high-density
      lipoprotein (HDL) cholesterol, triglycerides and low-density lipoprotein (LDL)
      cholesterol were measured in 16 healthy perimenopausal women (aged 47-56 years at
      menopause) who had undergone annual examinations 4 years before and 3 years after
      menopause under a health examinations system in Osaka. Longitudinal design
      enabled us to study the natural course of serum lipids and lipoproteins. The
      results show that from 4 years before to 1 year after menopause, the serum
      concentration of total cholesterol and LDL cholesterol increased on average by 25
      mg/dl (14%) and 20 mg/dl (19%), respectively. Serum concentrations of
      triglycerides and of HDL cholesterol remained virtually unchanged during the
      perimenopausal and postmenopausal periods. It was concluded that serum lipids and
      lipoproteins are thus significantly altered as a consequence of menopause,
      resulting in a more atherogenic profile in the postmenopausal period.

PMID- 8746877
TI  - Intrauterine administration of levonorgestrel in two low doses in HRT. A
      randomized clinical trial during one year: effects on lipid and lipoprotein
      metabolism.
AB  - OBJECTIVE: To investigate the effects on lipid and lipoprotein metabolism of two
      doses (5- or 10 micrograms/24 h) of levonorgestrel released from an intrauterine
      device (IUD) in combination with orally administered estradiol (2 mg estradiol
      valerate) in perimenopausal women. DESIGN: A 1-year prospective randomized single
      blind clinical trial. SETTING: Department of Obstetrics and Gynaecology, Ostra
      Hospital, Goteborg, Sweden. SUBJECTS: Fifty-one perimenopausal women with
      climacteric symptoms. OUTCOME MEASURES: Cholesterol in serum and in lipoprotein
      fractions; high-density lipoprotein (HDL), low-density lipoprotein (LDL).
      Triglycerides in serum and in very low-density lipoprotein. RESULTS: In both
      treatment groups significant elevations in HDL-cholesterol of similar magnitude
      were observed after 1 month and these changes were maintained during the 12 month
      observation period. In both treatment groups an initial significant decrease of
      LDL-cholesterol was observed and the decrement was maintained after 12 months.
      Serum levels of cholesterol decreased significantly in both groups after 1 month
      and were maintained after 12 months in the levonorgestrel-IUD (LNG-IUD) 5
      micrograms group. However, the initial reduction of serum cholesterol in the LNG
      IUD 10 micrograms group did not differ from baseline after 12 months. Serum
      triglyceride levels fluctuated during the observation period. No significant
      changes occurred. CONCLUSION: Continuous combined HRT with intrauterine
      administration of levonorgestrel, 5- or 10 micrograms/24 h, in perimenopausal
      women was observed to increase HDL-cholesterol and to decrease LDL-cholesterol
      compared with pretreatment values. The low doses of levonorgestrel did not
      reverse the beneficial effects on lipid metabolism usually seen after estradiol
      administration.

PMID- 8746878
TI  - Efficacy and tolerability of Menorest 50 compared with Estraderm TTS 50 in the
      treatment of postmenopausal symptoms. A randomized, multicenter, parallel group
      study.
AB  - Two-hundred and five (205) menopausal women with moderate to severe vasomotor
      symptoms, aged 39-64 years, were randomized from 20 clinical centers. After a 4
      week treatment-free period, each woman received a cyclical regimen (25 days of a
      4-week cycle) of Menorest 50, a new matrix-type transdermal estradiol system or
      Estraderm TTS 50, a marketed reservoir-type transdermal estradiol system twice
      weekly for 12 weeks. An oral progestin was also given for 10 days each cycle. The
      objectives were to compare local and systemic tolerability and efficacy in the
      treatment of menopausal symptoms. One-hundred and ninety-four [194] patients (96
      and 98 patients in the Menorest 50 and the reservoir transdermal patch groups,
      respectively) were considered in the intent-to-treat population and 204 (102 in
      each group) in the safety population. The two treatment groups were comparable
      with regard to the demographic data and menopausal status. The primary efficacy
      criteria were the comparison between Menorest 50 and the reservoir transdermal
      patch in erythema and pruritus at application sites and the difference between
      the treatment groups in the mean number of hot flushes per day at week 12,
      adjusted for baseline. A statistically significant reduction in the mean number
      of hot flushes was observed in each group compared with baseline, with a decrease
      from 6.5 at baseline to 0.3 at 12 weeks and 6.4 to 0.4 in the Menorest 50 and
      reservoir transdermal patch groups respectively; there was no statistically
      significant difference between the two groups during the 12-week treatment. The
      severity score of menopausal symptoms was also dramatically improved in each of
      the two treatment groups. There were no statistically significant differences in
      the mean plasma estradiol concentrations and mean estradiol to estrone ratio (>
      1.0) in both groups after 10 weeks of therapy. A similar number of adverse events
      was observed in both groups. Menorest 50 showed better local tolerability than
      the reservoir transdermal patch with a lower incidence of topical adverse events,
      erythema and pruritus. In summary, Menorest 50 was as effective as the reservoir
      transdermal patch in reducing the mean number of hot flushes, and improving the
      severity of other menopausal symptoms, including vasomotor, psychiatric and
      urogenital symptoms.

PMID- 8746879
TI  - The effect of percutaneous oestrogen replacement therapy on Lp(a) and other
      lipoproteins.
AB  - OBJECTIVES: To determine the effect of percutaneous oestrogen replacement therapy
      on lipoprotein (a) and other plasma lipoproteins. METHODS: Open longitudinal
      prospective study conducted at the hormone replacement clinic of the Prince of
      Wales Hospital, New Territories, Hong Kong. Thirty women who had undergone a
      total abdominal hysterectomy and bilateral salpingo-oophorectomy for benign
      gynaecological conditions were treated with 1.5 mg of percutaneous 17 beta
      oestradiol gel applied daily for a period of 12 consecutive months. Measurements
      of plasma lipoproteins were made before the commencement of treatment and
      repeated at 6- and 12-month intervals. RESULTS: There was a significant reduction
      in the concentrations of Lp(a) during the first 6 months of treatment, with
      median values falling from 7.87 mg dL-1 to 6.16 mg dL-1 (P = 0.004, 0-6 months).
      During the second 6 months, the median concentration increased to 9.38 mg dL-1,
      (P = 0.072, 6-12 months), which did not significantly differ from the baseline
      level (P = 0.545, 0-12 months). Significant reductions in the concentrations of
      apoprotein A-I (apo A-I), apoprotein B (apo B), high density lipoprotein
      cholesterol (HDL-C), and HDL3-C were also present after 6 months (P = 0.043,
      0.049, 0.028, 0.013, respectively), but there were no differences between the
      baseline values of these lipoproteins and those at the completion of the study (P
      = 0.948, 0.244, 0.839, 0.117 respectively). Drug compliance was maintained
      throughout the study, with similar mean oestradiol concentrations at 6 and 12
      months. CONCLUSIONS: The percutaneous administration of 17 beta-oestradiol has
      variable short term effects on plasma lipoproteins which are not maintained over
      a longer duration of treatment. By avoiding the 'first pass' effect on the liver,
      this method of delivery does not appear to produce the sustained changes in
      lipoproteins seen with oral treatment.

PMID- 8746880
TI  - Transvaginal estriol administration in postmenopausal women: a double blind
      comparative study of two different doses.
AB  - A group of 72 postmenopausal women were treated for 4 weeks with vaginal
      suppositories containing 0.5 or 1.0 mg of estriol. The two different doses
      achieved an identical significant improvement of urogenital symptoms, while a
      dose-related effect seen to be on climacteric complaints, according to a good
      absorption of estriol by the vaginal epithelium. Minimal side effects were
      observed and the safety of vaginal estriol treatment could advise further study
      about the effect of this kind of treatment on the climacteric syndrome.

PMID- 8746881
TI  - Transdermal estrogen for female stress urinary incontinence in postmenopause.
AB  - OBJECTIVE: To evaluate the effect of transdermal estrogen for stress urinary
      incontinence in postmenopause. STUDY DESIGN: An open within patient, dose-finding
      study with transdermal 17-beta-estradiol combined with cyclic medroxyprogesterone
      acetate was conducted over 9 months in 21 patients (mean age 57.3 years)
      suffering from urodynamically verified mild to moderate stress incontinence
      without detrusor instability. RESULTS: Subjective improvement was noted in 16 out
      of 21 patients (76%). The dose level of 50 micrograms was better tolerated than
      100 micrograms and sufficient enough to achieve continence. CONCLUSION:
      Transdermal estrogen therapy plays an adjuvant role in conservative therapy for
      mild to moderate stress urinary incontinence in postmenopausal women.

PMID- 8746882
TI  - Effects of hormone replacement therapy on growth hormone secretion patterns in
      correlation to somatometric parameters in healthy postmenopausal women.
AB  - OBJECTIVES: The aim of the present study was to investigate the influence of a
      continuous estrogen, cyclic progesterone replacement therapy on the secretion of
      growth hormone (GH) and IGF I as well as of somatometric-GH correlation patterns.
      METHODS: The study included 23 healthy postmenopausal women. Of the proband group
      13 randomly selected women were treated with orally applicated 2 mg estradiol
      valerat (E2V) and 10 mg dydrogesterone for 10 months. Ten women did not receive
      any hormonal treatment during this time. After 10 months all probands were
      reexamined and their GH and IGF I secretion, as well as their somatometric
      hormonal correlation patterns, compared with those of a fertile control group.
      RESULTS: It could be shown, that in postmenopausal women a 10-month oral hormone
      replacement therapy led to a significant increase of GH- and IGF I levels,
      however, the treated postmenopausal women did not reach the levels of the fertile
      controls. Those women who did not receive any hormonal treatment and the
      postmenopausal women before HRT showed nearly identical GH- and IGF I levels as
      well as somatometric-GH correlation patterns. CONCLUSIONS: The results of the
      present paper indicate a marked influence of estrogens on GH and IGF I secretion.
      Furthermore, hormonal replacement therapy (HRT) may influence somatometric GH
      correlation patterns too.

PMID- 8746883
TI  - Prevention of post-oophorectomy bone loss with Tibolone.
AB  - The results of a 1-year placebo-controlled study in 25 women who had hysterectomy
      and bilateral oophorectomy receiving a daily oral dose of 2.5 mg of Tibolone (Org
      OD 14) are presented. Tibolone is a steroid compound with mild oestrogenic in
      additional to progestagenic effects. Post-oophorectomy bone loss has been
      reported to accelerate, at least during the first year after surgery. The
      efficacy of Tibolone to prevent this accelerated bone loss is questionable. All
      patients were scheduled to participate in the study before oophorectomy. Patients
      had a detailed pre-operative examination, including measurement of forearm bone
      density with an SP2 Lunar single photon absorptiometer and haematological and
      biochemical investigation. After surgery, patients were randomly allocated in two
      groups; 15 women received an oral dose of 2.5 mg of Tibolone and 1000 mg of
      Calcium, while 10 women had only 1000 mg of calcium daily. Patients were examined
      at the end of 6 and 12 months of observation. Bone density of the radial shaft
      was found to decrease significantly in the calcium group up to 6.12% (P < 0.01)
      at the end of 6 months and 12.4% (P < 0.001) at the end of 12 months. On the
      other hand, bone density of the radial shaft remained unchanged in the Tibolone
      treated group during the 12 months of treatment. Bone density of the distal
      radius was found to decrease in the calcium-treated group up to 10.2% (P < 0.014)
      at the end of 6 months and up to 15.8% (P < 0.002) at the end of 12 months. Bone
      density of the distal radius remained almost unchanged in the Tibolone-treated
      group during the whole period of treatment. Urine hydroxyproline/creatinine ratio
      was found to increase in the calcium group at the end of 6 and 12 months (P <
      0.009) and to decrease significantly (P < 0.05) in the Tibolone-treated group. It
      is concluded that Tibolone is effective in the prevention of the post-ovariectomy
      accelerated bone loss and in retaining the initial premenopausal bone mass, at
      least during the first post-oophorectomy year. As this period is the most crucial
      in developing osteoporosis, it seems that Tibolone is effective in preventing the
      post-oophorectomy bone loss. HRT is not obligatory in these patients, as Tibolone
      seems to cover the whole spectrum of post-oophorectomy consequences.

PMID- 8746884
TI  - Insulin-like growth factor-binding protein-1: a biochemical marker of endometrial
      response to progestin during hormone replacement therapy.
AB  - OBJECTIVES: To compare immunohistochemical localization of insulin-like growth
      factor binding protein-1 (IGFBP-1) in endometrial stromal cells with endometrial
      morphology during three regimens of continuous combined hormone replacement
      therapy. METHODS: Endometrial samples for morphological examination and
      immunohistochemical staining with monoclonal antibody against IGFBP-1 were
      obtained from 30 menopausal women before treatment and after 12 and 24 months of
      continuous combined hormone replacement therapy. All women received percutaneous
      estradiolgel releasing 1.5 mg estradiol daily. Regarding progestins, patients
      were divided into three groups: one group (n = 15) had a 20 micrograms/24 h
      levonorgestrel-releasing intrauterine device (LNG-IUD); the women in the other
      two groups received micronised natural progesterone either 100 mg orally (n = 7)
      or 100-200 mg vaginally (n = 8) daily, 25 days per calendar month. RESULTS:
      Before treatment the endometrium of all women was atrophic or subatrophic and no
      IGFBP-1 could be detected in any of the samples which contained enough stromal
      cells for evaluation. After 12 and 24 months of treatment, epithelial atrophy
      with decidual transformation in stroma was detected in all specimens in the LNG
      IUD group, and IGFBP-1 was localized in decidualized stromal cells in all
      samples. In the other two groups, no signs of progestin effect were detected by
      microscopic examination in any of the endometrial samples and IGFBP-1 staining
      was completely negative in all of them. CONCLUSION: A striking difference
      occurred in both morphological and biochemical response in the endometrium of
      women treated with LNG-IUD compared with those receiving oral or vaginal
      micronised progesterone during continuous combined HRT. Micronised progesterone
      at doses used in this study turned out to be ineffective to prevent the
      proliferative effect of estrogen. Immunohistochemical localization of IGFBP-1 in
      endometrial stromal cells strongly correlated with decidual reaction in all
      endometrial specimens exposed to LNG-IUD, suggesting that the immunostaining of
      IGFBP-1 can be used as a means of assessing the strength of progestin effect in
      the endometrium during HRT.

PMID- 8746885
TI  - Multiple comparisons procedures for comparing several treatments with a control
      based on binary data.
AB  - In this paper, we examine three approaches for comparing several treatments with
      a control with use of binary response data. The first approach relies on
      asymptotic theory applied to the Freeman-Tukey transformation of the observed
      proportions. The second finds an acceptance region based on the binomial
      distributions estimated under the joint null hypotheses. The third approach
      applies Dunnett's procedure to the binary data. We evaluated the actual overall
      type I error rates of the Freeman-Tukey test and Dunnett's procedure using both
      simulation and binomial calculations while we assessed those of the binomial
      approach using simulation. Based upon their capability to preserve the desirable
      overall type I error rate, we provide recommendations regarding the choices among
      the three approaches for various occasions. In addition, we provide comments on
      the power of these three approaches.

PMID- 8746886
TI  - A Bayesian analysis of bivariate survival data from a multicentre cancer clinical
      trial.
AB  - I present an analysis of data from a clinical trial of new chemotherapies for
      colorectal cancer. I model participating clinical sites via random effects, to
      allow for heterogeneous patient responses across centres. Patient response is
      measured by both progression and survival times. The data suggest that patient
      responses are homogeneous before, but heterogeneous after, disease progression.
      For one new therapy, an increase in efficacy relative to standard therapy is
      detected before, but not after, progression.

PMID- 8746887
TI  - Comparison of median survival times with adjustment for covariates.
AB  - Brookmeyer and Crowley derived a non-parametric confidence interval for the
      median survival time of a homogeneous population by inverting a generalization of
      the sign test for censored data. The 1 - alpha confidence interval for the median
      is essentially the set of all values t such that the Kaplan-Meier estimate of the
      survival curve at time t does not differ significantly from one-half at the two
      sided alpha level. Su and Wei extended this approach to the two-sample problem
      and derived a confidence interval for the difference in median survival times
      based on the Kaplan-Meier estimates of the individual survival curves and a
      'minimum dispersion' test statistic. Here, I incorporate covariates into the
      analysis by assuming a proportional hazards model for the covariate effects,
      while leaving the two underlying survival curves virtually unconstrained. I
      generate a simultaneous confidence region for the two median survival times,
      adjusted to any selected value, z, of the covariate vector using a test-based
      approach analogous to Brookmeyer and Crowley's for the one-sample case. This
      region is, in turn, used to derive a confidence interval for the difference in
      median survival times between the two treatment groups at the selected value of
      z. Employment of a procedure suggested by Aitchison sets the level of the
      simultaneous region to a value that should yield, at least approximately, the
      desired confidence coefficient for the difference in medians. Simulation studies
      indicate that the method provides reasonably accurate coverage probabilities.

PMID- 8746888
TI  - Linear rank tests for doubly censored data.
AB  - This paper establishes the asymptotic properties of the non-parametric maximum
      likelihood estimator of the survival function based on data censored both from
      the left and the right. We show that the sample mean based on the survival
      estimator converges to a normal distribution, and we derive non-parametric tests
      for the differences in survival functions. The methods are applied to a study of
      dementia associated with Parkinson's disease.

PMID- 8746889
TI  - A new approach to selection and weighting of items in evaluative composite
      measurement scales.
AB  - Evaluative composite measurement scales (CMS) are increasingly used in medicine
      to measure complex constructs in the absence of a reference criterion or 'gold
      standard'. However, the level of measurement provided by these instruments has
      usually been given little attention. This paper explores the influence of the
      characteristics of the item set and weighting on the level of measurement of an
      evaluative CMS. The approach is illustrated with an application to the scoring
      system of the Nottingham Health Profile. Simulations are provided to indicate
      when the composite score of item responses, on an ordinal or pass-fail scale,
      could be considered to achieve the properties of an interval scale.

PMID- 8746890
TI  - Determining the value of additional surrogate exposure data for improving the
      estimate of an odds ratio.
AB  - We consider the design of both cohort and case-control studies in which an
      initial ('stage 1') sample of complete data on an error-free disease indicator
      (D), a correct ('gold standard') dichotomous exposure measurement (X) and an
      error-prone exposure measurement (Z) are available. We calculate the amount of
      additional information on the odds ratio relating D to X that one can obtain from
      a second ('stage 2') sample of measurements only on D and Z. If one allows for
      differential measurement error in Z, there is often little advantage in having
      more than four times as much data in stage 2 data as in stage 1. With the
      assumption that a non-differential measurement error model is reasonable, larger
      amounts of stage 2 data can be useful. Simulations indicate that stage 1 samples
      of modest size (50 cases in case-control studies and 50 failures in cohort
      studies) yield sufficiently reliable estimates of needed parameters to assist in
      determining an appropriate size for the stage 2 sample. These ideas apply in
      settings either where the amount of stage 1 data is limited and fixed by external
      constraints or where one has gathered stage 1 data in advance to avoid collecting
      superfluous stage 2 data.

PMID- 8746891
TI  - Using a mixture model to predict the occurrence of diabetic retinopathy.
AB  - Diabetes mellitus is a common condition which has several serious complications
      associated with it. In this paper a mixture model, based on one previously used
      to predict the onset of AIDS, is used to predict the onset of one of these
      complications, diabetic retinopathy, the major cause of adult blindness in the
      U.K. This model differs from the previous AIDS model by introducing covariates
      into the model and using a wider choice of mixture distributions. The fit and
      distributional assumptions of the model are then discussed for this example. The
      model is fitted to the data by maximum likelihood. It is important that the
      training set contains balanced numbers of individuals with and without
      retinopathy.

PMID- 8746892
TI  - Optimal and practicable designs for measuring plaque pH-profiles.
AB  - The shape of the plaque pH-profile after consumption of a food item determines
      the food's potential caries risk. This and related facts have caused an increased
      interest in measurements of plaque pH-profiles during the last decade. A standard
      design for these measurements is to take equally spaced observations over a
      certain period of time. The theory of optimal experimental design gives methods
      for positioning the measurements of a pH-profile in an optimized way. The
      objective is to minimize the effort given a desired precision of the estimated
      profile characteristic or to maximize the precision given the number of
      measurements. We show that a reduction in the number of measurements up to 50 per
      cent or a respective improvement in precision of the estimates as compared to
      standardly applied designs is possible. This implies less inconvenience for the
      subjects and better compliance with the needs of investigation. Our study is
      intended to demonstrate the applicability of the theory of optimal experimental
      design which has the potential to improve the efficiency of medical research.

PMID- 8746893
TI  - Restenosis after coronary interventions and device specificity.

PMID- 8746894
TI  - Exercise training and the autonomic nervous system in chronic heart failure.

PMID- 8746895
TI  - Resurrecting coronary angioplasty in acute myocardial infarction.

PMID- 8746896
TI  - Dynamic factors in the genesis of myocardial ischaemia.

PMID- 8746897
TI  - Subclassification of patients with angina and normal coronary angiograms.

PMID- 8746898
TI  - Imaging of aortic coarctation--difficult choices.

PMID- 8746899
TI  - Anticoagulation and pregnancy.

PMID- 8746900
TI  - Guidelines for prevention of thromboembolic events in valvular heart disease.
      Study Group of the Working Group on Valvular Heart Disease of the European
      Society of Cardiology.

PMID- 8746901
TI  - Differences in restenosis propensity of devices for transluminal coronary
      intervention. A quantitative angiographic comparison of balloon angioplasty,
      directional atherectomy, stent implantation and excimer laser angioplasty.
      CARPORT, MERCATOR, MARCATOR, PARK, and BENESTENT Trial Groups.
AB  - With the increasing clinical application of new devices for percutaneous coronary
      revascularization, maximization of the acute angiographic result has become
      widely recognized as a key factor in maintained clinical and angiographic
      success. What is unclear, however, is whether the specific mode of action of
      different devices might exert an additional independent effect on late luminal
      renarrowing. The purpose of this study was to investigate such a difference in
      the degree of provocation of luminal renarrowing (or 'restenosis propensity') by
      different devices, among 3660 patients, who had 4342 lesions successfully treated
      by balloon angioplasty (n = 3797), directional coronary atherectomy (n = 200),
      Palmaz-Schatz stent implantation (n = 229) or excimer laser coronary angioplasty
      (n = 116) and who also underwent quantitative angiographic analysis pre- and post
      intervention and at 6-month follow-up. To allow valid comparisons between the
      groups, because of significant differences in coronary vessel size (balloon
      angioplasty = 2.62 +/- 0.55 mm, directional coronary atherectomy = 3.28 +/- 0.62
      mm, excimer laser coronary angioplasty = 2.51 +/- 0.47 mm, Palmaz-Schatz = 3.01
      +/- 0.44 mm; P < 0.0001), the comparative measurements of interest selected were
      the 'relative loss' in luminal diameter (RLoss = loss/vessel size) to denote the
      restenosis process, and the 'relative lumen at follow-up' (RLfup = minimal
      luminal diameter at follow up/vessel size) to represent the angiographic outcome.
      For consistency, lesion severity pre-intervention was represented by the
      'relative lumen pre' (RLpre = minimal luminal diameter pre/vessel size) and the
      luminal increase at intervention was measured as 'relative gain' (relative gain =
      gain/ vessel size). Differences in restenosis propensity between devices was
      evaluated by univariate and multivariate analysis. Multivariate models were
      constructed to determine relative loss and relative lumen at follow-up, taking
      account of relative lumen pre-intervention, lesion location, relative gain,
      vessel size and the device used. In addition, model-estimated relative loss and
      relative lumen at follow-up at given relative lumen pre-intervention relative
      gain and vessel size, were compared among the four groups. Significant
      differences were detected among the groups both with respect to these estimates,
      as well as in the degree of influence of progressively increasing relative gain,
      on the extent of renarrowing (relative loss) and angiographic outcome (relative
      lumen at follow-up), particularly at higher levels of luminal increase (relative
      gain). Specifically, lesions treated by balloon angioplasty or Palmaz-Schatz
      stent implantation (the predominantly 'dilating' interventions) were associated
      with more favourable angiographic profiles than directional atherectomy or
      excimer laser (the mainly 'debulking' interventions). Significant effects of
      lesion severity and location, as well as the well known influence of luminal
      increase on both luminal renarrowing and late angiographic outcome were also
      noted. These findings indicate that propensity to restenosis after apparently
      successful intervention is influenced not only by the degree of luminal
      enlargement achieved at intervention, but by the device used to achieve it. In
      view of the clinical implications of such findings, further evaluation in larger
      randomized patient populations is warranted.

PMID- 8746902
TI  - Angiographic findings and catheterization laboratory events in patients with
      primary coronary angioplasty or streptokinase therapy for acute myocardial
      infarction.
AB  - BACKGROUND: The purpose of this study was to evaluate catheterization laboratory
      events and angiographic findings in patients randomly assigned to undergo primary
      coronary angioplasty or to receive intravenous streptokinase for acute myocardial
      infarction. METHODS: We analysed angiographic data in 301 patients with acute
      myocardial infarction, randomly assigned to undergo primary coronary angioplasty
      without antecedent thrombolytic therapy or to receive intravenous streptokinase
      therapy. Follow-up coronary angiography was preferably performed after 3 months.
      All angiograms were analysed with a quantitative coronary analysis system.
      RESULTS: Of the 152 patients assigned to angioplasty treatment, 140 underwent
      this procedure with a success rate of 97%. The residual diameter stenosis of the
      infarct-related vessel immediately after angioplasty was 27 +/- 15% and there
      were major events in 14% of the patients in the catheterization laboratory. At
      follow-up angiography after a mean interval of 92 days in the angioplasty
      assigned patients, a diameter stenosis of 35 +/- 22% was observed in this group.
      The restenosis rate was 28% and the reocclusion rate 5%. A Thrombolysis in
      Myocardial Infarction (TIMI) grade 2 flow immediately after angioplasty was
      predictive for reocclusion at follow-up (P = 0.001). In the streptokinase
      assigned patients (149) the infarct-related vessel was patent at follow-up
      angiography after a mean of 22 days in 66% of the patients with a mean residual
      diameter stenosis of 77 +/- 20%. CONCLUSION: Primary coronary angioplasty is a
      highly effective and safe reperfusion modality for patients with acute myocardial
      infarction. However, TIMI grade 2 flow through the infarct-related vessel
      immediately after angioplasty is a predictor of reocclusion.

PMID- 8746903
TI  - Autonomic balance in patients with angina and a normal coronary angiogram.
AB  - The pathophysiology of angina pectoris in patients with a normal coronary
      angiogram is not clear. Furthermore, the pathophysiological impact of ST changes
      in syndrome X is controversial. The purpose of this study was to investigate
      cardiac autonomic function, by measuring 24 h heart rate variability, in patients
      with and without electrocardiographic evidence of ischaemia during exercise.
      Thirty-two patients with angina pectoris, a normal coronary angiogram,
      echocardiogram, hyperventilation test and gastro-oesophageal investigation were
      studied. Fourteen healthy subjects served as controls. Fifteen patients had
      significant ST segment depression during stress testing, whereas 17 had no
      electrocardiographic signs of ischaemia. Heart rate variability was calculated as
      (1) mean RR = mean of all normal RR intervals, (2) the difference in mean RR
      level between when awake and when asleep (mean RR wake-sleep)-a tentative index
      of sympathetic activation, (3) the standard deviation (SD)-a broad band measure
      of autonomic balance, and (4) a percentage of successive RR interval differences
      > or = 6% (pNN6%)-an index of vagal modulation. The coronary vascular resistance
      was measured at rest and during pacing. Mean RR and autonomic indexes did not
      differ between patients with a positive exercise test and controls (831/884 ms;
      24 h SD 125/134 ms; pNN6% 6.715.4%, respectively). Patients with a normal
      exercise test had shorter mean RR (758 ms vs 844 ms; P < 0.05) and significantly
      reduced 24-h SD (103 ms vs 134 ms; P < 0.05) than controls, whereas values for
      vagal index (6.5% vs 5.4%) did not differ from healthy controls. Mean RR wake
      sleep also tended to be lower in patients with a normal exercise test (-125 ms vs
      -173 ms) compared to controls (P < 0.1). Patients with a positive exercise test
      had a significantly attenuated reduction in coronary vascular resistance during
      pacing in comparison to patients with a normal exercise test (-0.131 -0.26 mmHg x
      min. ml-1; P < 0.05). The findings suggest the occurrence of general elevated
      sympathetic activation in angina patients with a normal exercise test. Patients
      with a positive exercise test exhibited no signs of autonomic dysfunction
      although these patients had altered coronary vascular resistance indicating
      microvascular angina. This supports the suggestion that patients with a normal
      exercise test constitute an independent pathophysiological entity.

PMID- 8746904
TI  - Ergonovine-echo test to assess the significance of chest pain at rest without ECG
      changes.
AB  - The aim of this study was to assess the feasibility and diagnostic role of
      ergonovine maleate infusion under continuous two-dimensional echocardiographic
      monitoring for the identification of vasospastic myocardial ischaemia in patients
      with chest pain at rest not associated with diagnostic ECG changes. One hundred
      and twenty-eight consecutive patients, selected on the basis of absence of
      ischaemic ECG changes during angina at rest before or during hospitalization,
      were enrolled in the study. Ergonovine maleate was i.v. administered in scaled
      doses (from 0.025 to 0.2 mg at 10 min intervals) under echocardiographic,
      electrocardiographic and systemic blood pressure monitoring. Wall motion
      asynergies were observed in 33 patients, accompanied by typical chest pain in 24
      patients and by ECG changes in 25 (ST elevation in 13 patients, ST depression in
      seven, T wave changes in five). All patients were able to complete the test. Non
      life-threatening ventricular arrhythmias were observed in four patients
      exclusively in association with ischaemia. In seven patients with a positive
      test, coronary artery spasm was documented at angiography. In 16 patients with a
      positive test, the vasospastic event was reproduced by a hyperventilation-echo
      test or a second ergonovine maleate-echo test performed within 3 days of the
      first examination. In none of the patients with a negative test was documentation
      of myocardial ischaemia due to a primary reduction in coronary blood flow. Thus,
      in patients who do not show ECG changes during chest pain at rest, the ergonovine
      maleate-echo test is feasible and safe; it permits the recognition of ischaemic
      episodes on the basis of wall motion abnormalities when conventional 12-lead ECG
      recorded chest pain is non-diagnostic.

PMID- 8746905
TI  - Assessment of coronary artery stenosis during PTCA by measurement of the trans
      stenotic pressure gradient. Comparison with quantitative coronary angiography.
AB  - A fibreoptic pressure sensor mounted on an 0.018 inch guidewire (Pressure Guide,
      RadiMedical Systems, Uppsala, Sweden) was used to measure the trans-stenotic
      pressure gradient in 20 patients admitted for percutaneous transluminal coronary
      angioplasty (PTCA) of a single, discrete stenosis. Pressure measurements were
      made both at rest and during maximal vasodilatation induced by intracoronary
      injection of papaverine. From the ratio of distal coronary pressure divided by
      the proximal pressure, the relative coronary flow reserve was calculated. The aim
      of the study was to compare the different pressure-derived parameters by
      correlating them to stenosis geometry estimated by quantitative coronary
      angiography. There was a moderate correlation between baseline pressure gradient
      and percent area stenosis; r = 0.64, P < 0.001 and minimal cross-sectional area;
      r = 0.45, P < 0.005. A higher correlation was found between hyperaemic pressure
      gradient and area stenosis (r = 0.80, P < 0.001) and minimal cross-sectional
      areas, respectively (r = 0.55, P < 0.005). The best correlation was found between
      relative coronary flow reserve and area stenosis (r = 0.86, P < 0.001) and
      minimal cross-sectional area (r = 0.70, P < 0.001). In conclusion, pressure
      measurement using a pressure guidewire is useful as a complement to angiography
      in evaluation of coronary stenoses during PTCA. Pressures should be measured
      during maximal vasodilatation. Relative coronary flow reserve calculated from the
      pressure measurements provides additional information about the fraction of
      normal maximal flow possible in the presence of a stenosis.

PMID- 8746906
TI  - Lack of correlation between haemodynamic and cardiopulmonary exercise capacity
      improvement after catheter-balloon mitral valvuloplasty.
AB  - The long-term effects of percutaneous transvenous mitral commissurotomy on
      exercise capacity and ventilation were investigated to determine whether a
      dissociation between haemodynamic improvement and exercise capacity increase
      occurs in patients with mitral stenosis. Eighteen patients aged 45 +/- 12.3 years
      (mean +/- SD) with symptomatic mitral stenosis performed a symptom-limited
      bicycle exercise test while respiratory gases were measured before and 6 months
      after percutaneous transvenous mitral commissurotomy. The mitral valve area
      increased from 1.07 +/- 0.22 to 1.98 +/- 0.67 cm2. P < 0.0001 and the mean mitral
      gradient decreased from 12.9 +/- 4.5 to 5.3 +/- 4.8 mmHg, P < 0.001, without a
      significant increase in cardiac output index (from 2.64 +/- 0.55 to 2.77 +/-
      0.561, min-1, m-2, P = ns). This haemodynamic improvement was still present at
      the 6-month follow-up catheterization. Mean exercise workload and peak oxygen
      uptake increased 6 months after percutaneous transvenous mitral commissurotomy
      from 88.3 +/- 28.1 to 97.8 +/- 25.1 watts, P = 0.01, and from 18.1 +/- 5.3 to
      19.9 +/- 4.8 ml. kg-1. min-1, P < 0.05. Total ventilation, ventilatory
      equivalents and oxygen pulse at the end of the exercise test remained unchanged.
      Correlations between peak oxygen or exercise capacity improvement and mitral
      valve area increase were poor (r = 0.27, P = ns, r = 0.24, P = ns). This clear
      dissociation between haemodynamic improvement and improvements in minor exercise
      capacity after percutaneous transvenous mitral commissurotomy suggests that
      peripheral alterations persist. Future studies in which patients are trained
      after valvuloplasty may be helpful.

PMID- 8746907
TI  - Circadian pattern of heart rate variability in chronic heart failure patients.
      Effects of physical training.
AB  - The effect of physical training on the circadian pattern of heart rate
      variability (recorded over 24 h in relation to both time and frequency) was
      assessed in 12 chronic heart failure patients randomized, in a cross-over design,
      to 8 weeks training or detraining, and compared with 12 age-matched normals.
      Training improved heart rate variability indices: all R-R interval 5 min standard
      deviations increased by 17.6%, the root mean square of the differences of
      successive R-R intervals by 34.9%, the percentage difference between adjacent
      normal R-R intervals > 50 ms by 112.5%, total power by 58.3%, high frequency by
      128.5% and low frequency by 65.0%. Compared with controls, circadian variations
      in autonomic parameters were maintained in chronic heart failure. Training
      induced changes were observed at different time intervals throughout the day: the
      highest values were at 0100 h-0700 h (detraining: low frequency 361 +/- 83 ms2,
      high frequency 126 +/- 47 ms2; training: low frequency 535 +/- 202 ms2, high
      frequency 227 +/- 115 ms2, P < 0.01) and the lowest at 1300 h-1900 h (detraining:
      low frequency 91 +/- 23 ms2, high frequency 39 +/- 14 ms2; training: low
      frequency 154 +/- 42 ms2, high frequency 133 +/- 67 ms2, P < 0.05). In chronic
      heart failure, training maintains and improves circadian variations in heart rate
      variability measures.

PMID- 8746908
TI  - Prognostic factors of chronic heart failure in NYHA class II or III: value of
      invasive exercise haemodynamic data.
AB  - Various parameters have been found useful for establishing the prognosis of
      patients with chronic heart failure, in particular haemodynamic parameters
      measured at rest. However, few studies deal with the prognostic value of invasive
      exercise haemodynamic parameters in such patients. Our aim was to test the value
      of such parameters to assess the prognosis of patients with chronic heart failure
      in functional class II or III of the New York Heart Association. METHODS: Between
      December 1990 and June 1993, 50 patients fulfilled the criteria for inclusion in
      the study. The average age and ejection fraction of the population were 54 +/- 2
      years and 20 +/- 0.5% respectively. All patients were examined clinically; their
      invasive haemodynamic parameters were measured at rest and during exercise, and
      their exercise peak VO2, validated by reaching the anaerobic threshold, was
      determined. They were followed up for 21.2 +/- 1.17 months (ranges 3-26 months).
      The assessment criteria employed were mortality and the occurrence of major
      events (heart failure, pulmonary oedema or severe ventricular arrhythmia).
      RESULTS: The population consisted of 32 men and 18 women. No gender-related
      differences were found. Two groups could be distinguished in terms of prognosis:
      G1: n = 31 living patients with no events, and G2: n = 19 deceased or with major
      events. G1 and G2 were comparable with regard to age, sex ratio and ejection
      fraction. Several of the 52 parameters tested were different in the two groups,
      in particular peak VO2, exercise duration, the workload developed during the
      cardiopulmonary test and all the invasive exercise haemodynamic parameters except
      heart rate (P < 0.0001). Haemodynamic parameters at rest had no prognostic value
      in this series. The ROC curves, the survival curves and the Cox analysis showed
      that exercise cardiac power output, exercise left ventricular work indices and
      exercise peak VO2 were the most useful factors for assessing the prognosis of
      patients with NYHA II or III chronic heart failure. An exercise cardiac power
      output < 2 watts accurately identified those patients with a short-term poor
      prognosis, and exercise peak VO2 was almost as accurate. To a lesser extent, the
      NYHA functional class was also an independent prognostic parameter during
      multivariate analysis. In conclusion, it appears that invasive haemodynamic
      parameters are best for determining the prognosis of patients with chronic heart
      failure. Peak VO2 can, however, be as useful. Moreover this is an easily
      obtainable non-invasive parameter, which makes it more useful in the evaluation
      and the follow up of such patients.

PMID- 8746909
TI  - Biplane transoesophageal echocardiography, transthoracic Doppler, and magnetic
      resonance imaging in the assessment of coarctation of the aorta.
AB  - This study compared flow-sensitive magnetic resonance imaging with biplane
      transoesophageal echocardiography in combination with continuous wave Doppler
      from the suprasternal notch in patients with native coarctation or after surgical
      repair. Twenty patients (mean age 33 years, range 17-60) were investigated, of
      whom 15 had undergone surgery at mean age 13 years, range 5-43. Peak and mean
      flow in the ascending and descending aorta as well as coarctation peak velocity
      were determined with the magnetic resonance imaging phase contrast technique.
      Coarctation peak velocity was also measured by Doppler from the jugulum. Magnetic
      resonance imaging axial sections as well as biplane transoesophageal
      echocardiography were used to measure the smallest diameter of the constricted
      segment. Sixteen healthy volunteers, mean age 36 years, range 22-63, provided
      reference values for magnetic resonance imaging determined volume of flow in the
      aorta. Peak flow in the descending aorta was 9.2 +/- 3.7 l. min-1 (reference 13.0
      +/- 2.5, P < 0.01) and mean flow 3.1 +/- 0.9 l. min-1 (reference 3.4 +/- 0.8, P >
      0.05). The ratio of descending-to-ascending peak flow was 0.54 +/- 0.17
      (reference 0.69 +/- 0.10, P < 0.01) and mean flow 0.68 +/- 0.15 (reference 0.69
      +/- 0.08, P > 0.05). The coarctation velocity was slightly higher with Doppler
      than with magnetic resonance imaging (+0.24 +/- 0.44 m. s-1, 95% confidence
      interval +0.45 to +0.02 m. s-1, P = 0.05). The coarctation diameter was slightly
      larger with magnetic resonance imaging than with transoesophageal
      echocardiography (1.4 +/- 3.5 mm, 95% confidence interval +3.1 to -0.3 mm, P =
      0.11). Both methods are suitable for the assessment and follow-up of coarctation
      of the aorta. Flow assessment with magnetic resonance imaging provides a hitherto
      unavailable measure with which to assess the severity of obstruction.

PMID- 8746910
TI  - Sex-dependent differences in left ventricular function and structure in chronic
      pressure overload.
AB  - To evaluate gender-related differences in left ventricular (LV) structure and
      function in aortic stenosis, LV biplane cineangiography, micromanometry and
      endomyocardial biopsies were carried out in 56 patients with aortic stenosis and
      normal coronary arteries. Patients were divided into males (M: n = 35), and
      females (F: n = 21). Sixteen normal subjects 8 M, 8 F) served as haemodynamic
      controls. Control biopsy data were obtained from six pre-transplantation donor
      hearts (3 M and 3 F). LV systolic function was evaluated by ejection fraction and
      its relationship to mean systolic circumferential wall stress, diastolic function
      by the time constant of LV pressure decay, peak filling rates and passive
      myocardial stiffness constant. Biopsy samples were evaluated for interstitial
      fibrosis, muscle fibre diameter and volume fraction of myofibrils. In a subset of
      27 consecutive patients, biopsy samples were evaluated with a morphometric
      morphological method, for total collagen volume fraction, endocardial fibrosis
      and the extension and thickness of orthogonal collagen fibres (cross-hatching).
      In patients with aortic stenosis, aortic valve area, aortic valve resistance and
      mean aortic pressure gradient were comparable in males and females, whereas end
      systolic and end-diastolic volumes were larger in males than females. Ejection
      fraction was lower (56%) in males than females (64%) (P < 0.05); 20 of 35 males
      and four of 21 females had depressed systolic contractility when assessed with
      regard to the relationship ejection fraction-mean systolic stress (P < 0.01).
      Myocardial stiffness constant was higher in males than in females (P < 0.01).
      Nine of 14 males and two of 13 females had endocardial fibrosis (P < 0.009),
      whereas increased cross-hatching (> 1.5 grade) was present in 11 males and four
      females with aortic stenosis (P < 0.01). An abnormal collagen architecture was
      present in 13/14 males and 5/13 females (P < 0.002). In aortic stenosis, males
      have a depressed systolic function and abnormal passive elastic properties when
      compared to females with valve lesions of similar severity. Changes in collagen
      architecture may account, at least in part, for these differences.

PMID- 8746911
TI  - Dobutamine echocardiography: usefulness of digital image processing.
AB  - The present study was undertaken in order specifically to evaluate the usefulness
      of digital image processing so as to enhance the diagnostic power of dobutamine
      stress echocardiography. For this purpose 44 dobutamine echocardiographic tests,
      routinely performed in our echo laboratory, were analysed blindly by two
      observers using traditional videotape recording and digitized image acquisition.
      The results obtained from both observers show a trend which suggests that the
      traditional videotape approach provides more true-positive tests than the
      digitized approach (27/38 vs 23/38 and 24/38 vs 22/38 for the first and second
      observer, respectively). True-negative test detection was 6/6 with the videotape
      and 5/6 with the digitized method for both observers. As a consequence of the
      discrepancies observed between the two modalities, the videotape indicates that
      it can provide higher diagnostic accuracy than the digitized approach (72 +/- 9%
      vs 63 +/- 10%). The tests results concordance (positive or negative) between the
      two modalities of analysis was 66% for both the observers. The inter-observer
      agreement on the test results was 84% and 80% for the videotape analysis and the
      digitized analysis, respectively. On the basis of the results, we consider that
      digitized analysis applied to dobutamine stress echocardiography does not afford
      significant diagnostic advantages and should not be considered as an alternative
      option to traditional videotape analysis. However, it may be considered an
      extremely useful integrative tool since it produces the on-line image evaluation
      more easily and faster and allows a more practical form of stress test storage.

PMID- 8746912
TI  - The determination of volume of right ventricular casts using a conductance
      catheter.
AB  - Conductance catheters were used to assess the volume of right ventricular models
      made from post-mortem casts. Models were made from silastic rubber and filled
      with saline. The correlation between volume assessed by conductance catheter and
      real volume was investigated as saline was withdrawn from, and injected into,
      five models. The mean regression between real and conductance-derived volume was
      1.05 (SE 0.04 mean R2 0.94 SE 0.02) with Y-intercept -0.25 ml SE 1.72. Parallel
      wall conductance was assessed through the tricuspid orifice sealed with human
      tricuspid tissue, or left open, and found to be negligible. There was no
      difference between volumes measured by a catheter through either the pulmonary or
      tricuspid orifice. We conclude that conductance catheters are suitable for the
      assessment of right ventricular volume, despite the complex geometry.

PMID- 8746913
TI  - Rapid diminution of calcium in the myocardium by transfer to pericardial
      solutions. Myocardial dialysis.
AB  - A new method is described for the controlled and specific depletion of calcium
      from the vascularly perfused heart of experimental animals by means of dialysis,
      using a pericardial solution. A 30-40 ml isotonic phosphate buffer pH 7.3 with a
      low Ca2+ and high Mg2+ concentration (0.2 and 2.7 mM respectively) was inserted
      into the pericardial cavity of anaesthetized dogs and kept there for 10 or 60
      min. The calcium content of the subendocardial and subepicardial halves of the
      left ventricular wall was similarly decreased to about 70% (P < 0.01) within 10
      min and to 62% (P < 0.001) at 60 min, compared to that of hearts dialysed for 60
      min in a standard solution of Ca2+ 1.2 mM and Mg2+ 1 mM. Calcium content of the
      myocardium dialysed with low Ca2+ and a standard Mg2+ solution decreased to only
      75% (P < 0.01) at 60 min. Similar changes of calcium were measured in other parts
      of the heart. An increase in Ca2+ concentration in the pericardial solution was
      observed at the same time as a decrease in calcium in the myocardium. The
      increase in Ca2+ reached about 0.7 mM at 60 min, but decreased slightly, and
      finally, fell to 85% of pre-dialysis values at 60 min. It is concluded that this
      method of myocardial dialysis is effective in reducing myocardial calcium and is
      influenced by the duration of dialysis and the Mg2+ content of dialysate.

PMID- 8746914
TI  - Myxoma of the mitral valve detected by echocardiography and magnetic resonance
      imaging.
AB  - Myxomas of the mitral valve diagnosed during life are exceedingly rare. We
      employed transthoracic and transoesophageal echocardiography and magnetic
      resonance imaging enhanced by gadolinium-diethylene-triamine-pentaacetic acid in
      a patient with palpitations. After these examinations clearly demonstrated a
      myxoma on the atrial side of the posterior mitral valve leaflet, urgent surgery
      was performed. When a small tumour of the mitral valve exists, these examinations
      are useful not only for detecting and characterizing the tumour, but also for
      deciding the optimal surgical management.

PMID- 8746915
TI  - Dynamic left ventricular outflow tract obstruction after anterior myocardial
      infarction. A potential mechanism of myocardial rupture.
AB  - This study describes a dynamic left ventricular outflow tract gradient
      complicating an acute anterior myocardial infarction in two patients. In both
      cases, hyperdynamic contraction of the non-infarcted segments were noted in
      addition to large antero-apical a- or dyskinesia. Both patients had evidence of
      mitral annular calcifications, and the occurrence of dynamic outflow tract
      obstruction preceded sudden death. Early recognition of the underlying
      pathophysiological mechanism might have major therapeutic implications and could
      decrease the risk of myocardial rupture.

PMID- 8746916
TI  - The descending septal branch (Bonapace's branch). A case report and literature
      review of this often forgotten branch. First description in vivo.
AB  - We present a 51-year-old female with exertional angina pectoris and a normal
      coronary angiogram who had a prominent descending septal branch originating from
      the proximal right coronary artery. This branch was perfused in the antegrade
      direction and did not show the tortuosity typical of coronary collaterals. The
      branch was almost 1 mm in diameter and supplied the middle third and basal two
      thirds of the interventricular septum. The right coronary artery and this branch
      were free of coronary obstructions. The descending septal branch, described in
      1921 by Crainicianu in a postmortem study, occurs in 12 to 85% of human hearts,
      but is still widely unknown. A review of the literature is also provided with
      special consideration of the functional importance of the condition and its
      prevalence in human and animal hearts. As far as we are aware, such a well
      developed descending septal branch in human hearts has not been described before.
      This is also the first description of a descending septal branch in vivo.

PMID- 8746917
TI  - Atypical presentation of adult Still's disease mimicking acute bacterial
      endocarditis.
AB  - Adult Still's disease is a chronic, systemic disease of unknown origin. We
      describe the case of an otherwise healthy man with an uncommon presentation of
      Still's disease. A 38-year-old man presented with sore throat, fever, rash and
      arthritis. Laboratory findings showed that both erythrocyte sedimentation rate
      and ferritin had increased. Transoesophageal echocardiography revealed a
      vegetation involving the aortic leaflet. The diagnosis of Still's disease was
      made after the exclusion of infectious endocarditis, based upon the clinical
      picture, the high level of ferritin and the follow-up. The patient markedly
      improved after treatment with prednisone 1 mg. kg-1. This controlled and then
      progressively reduced the disease; the drug was then withdrawn. This case
      illustrates that Still's disease can present with endocardial involvement
      mimicking acute bacterial endocarditis as a first clinical manifestation. The
      observation suggests that the presence of high ferritinaemia in a patient with
      some clinical criteria of Still's disease could lead to an early diagnosis.

PMID- 8746918
TI  - Effects of access to a running wheel on food, water and ethanol intake in rats
      bred to accept ethanol.
AB  - Rats from the University of Indiana lines bred to accept ethanol (P rats) and not
      to accept ethanol (NP rats) were divided into two groups of 3 rats per group. The
      first group of P and NP rats was given free access to food, water and 5% (w/v)
      ethanol 24 h a day. After food, water and ethanol intake stabilized, a running
      wheel was introduced into the cage. Access to the running wheel decreased ethanol
      intake and increased water intake in P rats. When the running wheel was locked in
      place, ethanol intake by P rats increased, but when the wheel was unlocked again,
      no decrease in ethanol intake occurred. Access to the running wheel did not
      affect food, water or ethanol intake in NP rats. The decrease in ethanol intake
      when the running wheel was introduced was replicated in the second group of P
      rats exposed to 5% ethanol and later to 10% ethanol. The decreases in ethanol
      consumption produced by the introduction of a running wheel for this genetic
      model of alcohol consumption are similar to those previously reported using
      schedule-induced polydipsia to induce ethanol intake.

PMID- 8746919
TI  - Early-onset drug use and risk of later drug problems.
AB  - Prior research has suggested that among illicit drug users there is an increased
      risk of drug abuse or dependence problems associated with earlier onset of
      illicit drug taking. This study examined whether the observed association might
      be understood best as the result of a process by which earlier onset users
      accumulate more time during which they can develop a drug problem (that is, more
      time since first illicit drug taking). Survival data analysis was employed to
      investigate this issue, with self-report data from 1525 illicit drug using
      individuals, all of whom were 18-24-year-old participants in the multi-site
      collaborative Epidemiologic Catchment Area Program. In the first year after
      initial illicit drug use, there was no appreciable variation in the estimated
      risk of developing a drug problem. However, with passage of some 5-7 years after
      initial use, the estimated risk of developing drug problems became clearly
      greater for youths whose drug taking had started during the pre-adolescent and
      very early adolescent years. The previously reported relationship between early
      onset drug use and subsequent drug problems was not, therefore, an artifact of
      time. It is possible that duration of drug use should be considered as one
      'mechanism' by which early-onset drug users experience greater risk of drug
      problems, but there also are other interpretations to be investigated in future
      research.

PMID- 8746920
TI  - A placebo controlled clinical trial of buprenorphine as a treatment for opioid
      dependence.
AB  - Large-scale placebo controlled clinical trials assessing the efficacy of
      medications for the treatment of drug dependence have generally been limited to
      alcohol, cocaine and nicotine dependent populations. The purpose of the present
      study was to assess the early (1-2 week) clinical effectiveness of buprenorphine
      versus placebo in an opioid dependent population. The study used a parallel-group
      design with a behavioral choice component to compare buprenorphine (a mu-opioid
      partial agonist) to placebo for the treatment of opioid dependence. Opioid
      dependent volunteer patients participated in a 14-day study to assess the
      effectiveness and patient acceptance of this new pharmacotherapy for the
      treatment of opioid dependence. Patients were randomly assigned to placebo (n =
      60) or 2 mg (n = 60) or 8 mg (n = 30) daily sublingual buprenorphine. All doses
      were administered double-blind. On days 6-13 all patients could request a dose
      change, knowing that their new dose would be randomly chosen from the remaining 2
      alternatives. Compared to placebo, patients given buprenorphine (independent of
      dose) showed greater time on initial dose, requested fewer dose changes, used
      less illicit opioids (assessed by urinalysis), and rated dose adequacy higher.
      These results demonstrate that a placebo controlled study with a behavioral
      choice component is an effective means of assessing the potential efficacy and
      acceptability of new pharmacotherapies for opioid dependence.

PMID- 8746921
TI  - Buprenorphine treatment of opioid dependence: clinical trial of daily versus
      alternate-day dosing.
AB  - Buprenorphine, a mu-opioid partial agonist, has demonstrated efficacy for the
      treatment of opioid dependence comparable to that of methadone. The clinical
      utility of buprenorphine would be enhanced if it could be dosed on a less than
      daily basis. The current study is a parallel-group outpatient clinical trial of
      daily versus alternate-day dosing with 8 mg sublingual (s.l.) buprenorphine.
      Participants were randomly assigned to daily (n = 51) or alternate-day (n = 48)
      schedules of active medication administration for an 11-week double-blind trial.
      Patients assigned to alternate-day buprenorphine received placebo every other
      day. Primary outcome measures were retention in treatment and urine specimens
      positive for opiates. Clinic attendance, dose adequacy ratings, withdrawal
      symptomatology, and urine specimens positive for cocaine were secondary outcome
      measures. Neither endpoint analysis with the intent-to-treat sample nor time
      course analysis with treatment completers revealed any statistically significant
      differences between the dosing schedules on any outcome measure. Examination of
      95% confidence intervals suggested a non-significant trend for the daily dosing
      schedule to have superior clinical efficacy at the dose tested. Nevertheless,
      these results are generally consistent with previous studies of less than daily
      dosing with buprenorphine and support the conclusion that an alternate-day dosing
      schedule can be effective in and acceptable to a substantial portion of patients.

PMID- 8746922
TI  - Subcutaneous injection of an analog of neuropeptide FF prevents naloxone
      precipitated morphine abstinence syndrome.
AB  - There is evidence that neuropeptide FF (NPFF) has antiopiate activity and may
      play a role in opiate dependence and subsequent abstinence syndrome. A fragment
      of NPFF was modified at the C-terminal in an effort to convert it to an NPFF
      antagonist. It was also dansylated at the N-terminal in an effort to render it
      more lipophilic and increase its penetration of the blood-brain barrier. Third
      ventricle administration of the resulting compound, dansyl-PQRamide (0.75
      microgram and 1 microgram), dose-dependently antagonized the quasi-morphine
      abstinence activity of NPFF (10 micrograms) in opiate-naive rats. Subcutaneous
      injection of dansyl-PQRamide (13 mg/kg) in chronically morphine-infused rats
      attenuated opiate dependence as indicated by prevention of naloxone-precipitated
      abstinence syndrome. Dansyl-PQRamide displaced radiolabelled ligand from NPFF
      receptors in a concentration-dependent manner with a Ki of 13 microM, and had a
      half-life over 300 times longer than NPFF under aminopeptidase digestion.

PMID- 8746923
TI  - Alpha 1-adrenergic receptor antagonist blocks acute cocaine action on the
      compound action potential of the auditory nerve in the chinchilla.
AB  - Acute systemic cocaine injection is known to significantly decrease the compound
      action potential (CAP) amplitude of the auditory nerve. In an attempt to
      elucidate the mechanism underlying this phenomenon, the present study
      investigated the influence of prazosin, an adrenergic alpha 1-receptor
      antagonist, on the effect of cocaine on the CAP. Amplitude-intensity functions at
      1 and 8 kHz were obtained before and after treatment with cocaine (experimental
      group) or saline (control group) in prazosin pretreated subjects. The
      characteristic reduction in CAP amplitude after an acute cocaine injection was
      blocked by 0.05 mg/kg prazosin. When subjects were re-injected with cocaine or
      saline one h after prazosin, the reduction in CAP amplitude following cocaine
      injection had recovered.

PMID- 8746924
TI  - Alcohol dependence, family history, and D2 dopamine receptor function as
      neuroendocrinologically assessed with apomorphine.
AB  - Fifteen alcohol dependent men with an alcohol dependent first degree relative
      (i.e. family history positive or FHP), 15 well matched alcohol dependent men
      without a family history for alcohol dependence (i.e. family history negative or
      FHN), and 15 healthy controls (CONTR) participated in this study. The three
      groups were compared according to their postsynaptic D2 dopamine receptor
      function as assessed by growth hormone release after stimulation with the
      dopamine receptor agonist apomorphine. Statistical evaluation was done by planned
      comparisons within a one-way ANOVA. Alcohol dependent subjects significantly
      differed from CONTRs as long as family history was not taken into account (t(42)
      = 2.38; P = 0.022*). When differentiating according to family history, both FHPs
      and FHNs maintained a blunted growth hormone response. However, the difference
      between FHNs and CONTRs, though present, dropped out of statistical significance
      (t(42) = 1.65; P = 0.105); at the same time, the difference between FHPs and
      CONTRs became slightly stronger (t(42) = 2.47; p = 0.017*). In conclusion, our
      data give neuroendocrinological support to the assumption that a reduced D2
      dopamine receptor function in alcohol dependent men is not only a state marker of
      residual heavy drinking but also a genetically determined trait marker.

PMID- 8746925
TI  - Evaluation of a point-of-care testing product for drugs of abuse; testing site is
      a key variable.
AB  - We evaluated the EZ-SCREEN Test Kit (Editek, Inc., Burlington, NC), a point-of
      care screening test for the presence of cocaine metabolite (benzoylecgonine; BE),
      cannabinoids (tetrahydrocannabinol; THC) and opiates in urine. Patient specimens
      (n = 34) were tested in the laboratory using both Abbott Laboratories ADx (ADx)
      and EZ-SCREEN (EZS-LAB), and by the nursing staff of an inpatient substance abuse
      treatment program using the EZ-SCREEN (EZS-RN). We found comparable analytical
      efficiency between methods used in the laboratory (> 95% for all three analytes
      with EZS-LAB and ADx) but lower efficiency for THC and BE with point-of-care
      testing (approximately 82% for EZS-RN). Efficiency for EZS-RN opiates was 100%.
      We conclude that the EZ-SCREEN Test Kit may not be suitable for use in a busy
      clinical setting, unless specific measures are taken to insure the accuracy of
      point-of-care testing (e.g., minimal interruption or distraction, careful
      training). We recommend that prior to routine use of point-of-care testing
      products they be evaluated under normal working conditions with personnel who
      will eventually be required to perform routine testing.

PMID- 8746926
TI  - Prospective evaluation of a model of risk for HIV infection among injecting drug
      users.
AB  - Data on 3016 out-of-treatment injecting drug users (IDUs) were analyzed in order
      to replicate findings from an earlier study on risk factors for HIV infection
      (Iguchi et al., 1992) and evaluate a model for estimating probability of
      infection. Logistic regression analyses yielded a set of risk factors highly
      consistent with previous findings. A logistic function was used to estimate
      subjects' probabilities of infection, and these estimates were strongly
      correlated with actual HIV prevalence in both the original and current samples.
      The current study represents a successful replication of earlier findings and
      supports the validity of the risk model.

PMID- 8746927
TI  - Increased aggressive responding in male volunteers following the administration
      of gradually increasing doses of testosterone cypionate.
AB  - The present study assessed the effects of supraphysiologic doses of testosterone
      on aggressive responding in a controlled laboratory setting. Eight male subjects
      received gradually increasing doses of testosterone cypionate (150 mg/week for
      two weeks, 300 mg/week for two weeks, and 600 mg/week for two weeks) or placebo
      using a double-blind, randomized, cross-over design. Subjects were tested both
      before and after the series of injections. During the experimental session
      subjects could press a button to accumulate points exchangeable for money (non
      aggressive response) or press another button to subtract points from a fictitious
      opponent (aggressive response). Aggressive responding was instigated by
      subtracting points from the subject which was attributable to the fictitious
      opponent. Testosterone administration resulted in a significantly higher number
      of aggressive responding compared to placebo.

PMID- 8746929
TI  - Buprenorphine-induced alterations of cocaine's reinforcing effects in rhesus
      monkey: a dose-response analysis.
AB  - Buprenorphine reduces cocaine self-administration by rhesus monkeys, opiate- and
      cocaine-dependent men and polydrug abusers, but the mechanisms underlying these
      cocaine-opiate interactions are not well understood. In the present study, the
      effects of daily placebo or buprenorphine (0.1, 0.3 and 1.0 mg/kg) treatment on
      cocaine self-administration (0.001-0.3 mg/kg/inject) were examined in five
      cocaine-experienced rhesus monkeys. Saline and each of six cocaine doses were
      available in an irregular order. Responding for cocaine (or saline) and food was
      maintained on a second order FR4 (VR 16:5) schedule of reinforcement. During
      placebo treatment, the daily number of cocaine injections increased as the unit
      dose was increased and then decreased at higher doses. Cocaine doses that
      maintained the highest rates of responding during placebo treatment were more
      resistant to buprenorphine's effects. The typical increase in response rate
      during the first five cocaine injections of a session also was attenuated by
      buprenorphine. The ascending limb of the cocaine dose-response curve was shifted
      downward and approximately one log unit to the right during low-dose
      buprenorphine treatment (0.1 mg/kg/day). In contrast, individual response rates
      for food pellets were unaffected. We conclude that buprenorphine selectively
      decreases self-administration of some unit doses of cocaine at doses that have
      minimal effects on food-maintained responding.

PMID- 8746928
TI  - Pharmacological specificity of the discriminative stimulus effects of delta 9
      tetrahydrocannabinol in rhesus monkeys.
AB  - delta 9-Tetrahydrocannabinol (delta 9-THC) discrimination has been used as an
      animal model of cannabis intoxication in humans. While numerous studies have
      examined the discriminative stimulus effects of cannabinoids in rats and pigeons,
      studies with monkeys have been rare. In the present study, rhesus monkeys,
      trained to discriminate delta 9-THC from vehicle in a two-lever drug
      discrimination procedure, were tested with a variety of psychoactive drugs,
      including cannabinoids as well as drugs from other classes. Results showed that
      delta 9-THC discrimination showed pharmacological specificity, in that none of
      the non-cannabinoid drugs fully substituted for delta 9-THC. In contrast, the
      classical cannabinoids, delta 9-THC and delta 8-THC, and the novel cannabinoids,
      WIN 55212-2 and 1-butyl-2-methyl-3-(1-naphthoyl)indole, produced full dose
      dependent substitution for delta 9-THC in all monkeys. A heptyl indole derivative
      failed to substitute for delta 9-THC, but it also did not displace [3H] CP 55940
      from its binding site. These findings are consistent with those of previous
      cannabinoid discrimination studies with rats and suggest that results of delta 9
      THC discrimination studies in rhesus monkeys may be predictive of the subjective
      effects of cannabinoid drugs in humans.

PMID- 8746930
TI  - The multicentre trial philosophy in stress echocardiography: lessons learned from
      the EPIC study. EPIC-EDIC Study Project. Echo Persantine International
      Cooperative Study. Echo-Dobutamine International Cooperative Study.
AB  - The scientific assessment of diagnostic tests should not be based upon a small
      series of results published by the best academic institutions, but ought to
      require large scale, multicentre validation founded on grass roots institutions
      with real doctors, real patients and real problems. To this purpose, an
      international network of stress echo laboratories has been organized, and within
      a few years has collected data from thousands of studies using pharmacological
      stress echocardiography, performed with either dipyridamole (EPIC: Echo
      Persantine International Cooperative Study) or dobutamine (EDIC: Echo Dobutamine
      International Cooperative Study) stresses. In a widely deregulated field, all
      network laboratories have agreed: to pass a quality control examination on stress
      echo reading before entering the study; to adopt an identical drug infusion
      protocol; to code similarly the LV segments; and to adopt a common scoring system
      for wall motion analysis. A minimum amount of historical, clinical, and-when
      available-stress electrocardiographic, angiographic and follow-up data have been
      collected on each patient, and disseminated in the various centres, facilitating
      the creation of an international stress echo language that will help, not only
      the production of high quality scientific data, but also the build up of a common
      stress echo lab, with a standardized way of making the studies, unifying the
      methods and terminology, and archiving data. To date, we have 50 echo
      laboratories from 15 nations across four continents (Europe, America, Asia and
      Africa) actively involved in this project. These data will ultimately fill the
      gap between the academic theory of journals and the pragmatic experience of daily
      life in a busy echocardiographic laboratory.

PMID- 8746931
TI  - Emerging technology in stress echocardiography.
AB  - Stress echocardiography has seen substantial expansion as a clinically useful
      tool for evaluation of patients with chest pain syndromes, determining the
      physiological significance of coronary artery lesions and assessing prognosis in
      patients known to have coronary disease. Several newly developing technologies
      show promise for enhancing the accuracy and clinical applicability of the
      examination. These include automatic edge detection systems, intravenous contrast
      for enhanced endocardial definition, tissue Doppler imaging, and tissue
      characterization techniques. Finally, new methods of cardiovascular stress,
      including combinations of exercise and pharmacological agents as well as newly
      developed pharmacological agents, also show promise for enhancing the clinical
      utility of stress echocardiography.

PMID- 8746932
TI  - Diagnosis of coronary artery disease and viable myocardium by stress
      echocardiography. Diagnostic accuracy of different stress modalities.
AB  - Stress echocardiography is being used more commonly for routine clinical
      diagnosis of coronary artery disease. In addition to physical treadmill or
      bicycle exercise echocardiography, pharmacological stress echocardiography with
      dobutamine and dipyridamole has also gained increasing significance over the past
      few years. Numerous studies have proven that these methods diagnose coronary
      artery disease accurately (exercise echocardiography: sensitivity 71 to 98%,
      specificity 64 to 100%, dobutamine echocardiography; sensitivity 54 to 96%,
      specificity 66 to 95%; dipyridamole echocardiography: sensitivity 57 to 74%,
      specificity 80 to 100%), but no direct comparison has hitherto been able to prove
      the superiority of any one of these protocols. However it is recognized that the
      skill and experience of the echocardiographer performing this study has an
      influence on the accuracy of the technique.

PMID- 8746933
TI  - Characterization of hibernating and stunned myocardium.
AB  - Both the hibernating and the stunned myocardium are characterized by reversible
      contractile dysfunction. In hibernating myocardium, perfusion is still reduced,
      whereas in stunned myocardium blood flow is fully or almost fully restored. Both
      the hibernating and the stunned myocardium retain an inotropic reserve. In
      hibernating myocardium the increase in contractile function is at the expense of
      metabolic recovery, whereas in the stunned myocardium no metabolic deterioration
      occurs during inotropic stimulation. Therefore, inotropic stimulation in
      combination with metabolic imaging may help not only to identify viable,
      dysfunctional myocardium but also to distinguish hibernating and stunned
      myocardium. The therapy of hibernating myocardium is to restore blood flow to the
      hypoperfused tissue. Myocardial stunning per se requires no therapy at all,
      since, by definition, blood flow is normal and contractile function will recover
      spontaneously. If, however, myocardial stunning is severe, and it involves large
      parts of the LV and thus impairs global LV function, it can be reversed with
      inotropic agents and procedures. In the experimental setting, anti-oxidant
      agents, calcium antagonists and ACE inhibitors attenuate stunning, but most
      effectively when administered before ischaemia.

PMID- 8746934
TI  - Dipyridamole and dobutamine: competitors or allies in pharmacological stress
      echocardiography?
AB  - Stress echocardiography has become an accepted and cost-effective method for
      diagnosing coronary artery disease. However, as exercise stress echocardiography
      is a demanding technique, difficult to reproduce, pharmacological stress
      echocardiography has become very popular in recent years. The two most popular
      tests from the pharmacological stress echocardiography arena are dipyridamole and
      dobutamine. They have enabled the technical limitations inherent in exercise
      echocardiography to be overcome, and have provided the opportunity to obtain,
      during stress, images of unchanged quality in comparison to baseline. However,
      the sensitivity of both pharmacological stresses applied separately is less than
      ideal in patients with milder forms of coronary artery disease and in patients
      under therapy. To overcome this, a new generation of pharmacological stress
      tests, the combined dipyridamole-dobutamine tests were introduced. A combined
      dipyridamole-dobutamine echocardiography stress test should suggest that the
      agents are natural allies rather than competitors but in some instances they are
      applicable only in selected patients, and each pharmacological agent may be
      clinically contraindicated for administration. This is the message from a large
      scale study of recent years.

PMID- 8746935
TI  - Functional assessment of PTCA results by stress echocardiography: when and how to
      test.
AB  - Angiographic follow-up has shown that restenosis after PTCA is a continuous and
      ubiquitous process rather than a dichotomous event. Since the functional
      significance of restenosis involves more factors than minimal lumen diameter,
      functional tests after PTCA cannot be expected to match exactly the degree of
      angiographic restenosis. In the past, nuclear perfusion imaging has been the most
      accurate non-invasive method to predict restenosis, but now there is a new
      technique: stress echo. This uses physical (treadmill, exercise), pharmacological
      (dipyridamole, dobutamine), or pacing stress (together with transoesophageal
      imaging) for the detection of stress-inducible wall motion abnormalities;
      resolution of resting abnormalities may also be observed. These stress modalities
      have been employed to detect restenosis in limited numbers of patients, with
      diagnostic accuracies (so far, except for dobutamine) comparable to nuclear
      imaging. Therefore, it seems that the decision to use echo stress testing depends
      on patient characteristics, availability of methods, and, importantly, experience
      of the echo laboratory. Timing of the test after PTCA must take into account
      delayed functional recovery after PTCA; this has been well described by nuclear
      perfusion imaging. Thus, very early (< 1 month) tests lack specificity. On the
      other hand, development of restenosis after 6 months is rare. Stress tests
      therefore should be performed within the time window of 1 to 6 months after PTCA.

PMID- 8746936
TI  - Automated contour detection and acoustic quantification.
AB  - Echocardiographic left and right ventricular sequences are usually interpreted
      visually, but current quantitation techniques have been found to be tedious, time
      consuming and associated with significant inter- and intra-observer
      variabilities. In an attempt to eliminate these problems, we have developed the
      Echocardiographic Analysis System (EAS) which uses robust automated border
      detection techniques both for single frames as well as for sequences. Comparison
      of LV cross-sectional area with the semi-automated border detection (AUTO) and
      those assessed from manual tracings (MAN) yielded a systematic difference (MAN
      AUTO) of -6.6% (p < 0.001), and a random difference (standard deviation of paired
      signed differences) of 11.8%. Current developments are directed towards real-time
      automated border detection with an Accelerator board, integration of Acoustic
      Quantification (AQ) data as edge information into EAS, and intravascular
      echocardiographic applications.

PMID- 8746937
TI  - Quantitative aspects in myocardial contrast echocardiography.
AB  - Myocardial tissue perfusion is not currently quantified in the clinical setting.
      Thus the aim of this paper is to review the quantitative information on
      myocardial perfusion provided by contrast echocardiography. In a circulatory
      model-without the capillary network interposed between injection and sampling
      point of contrast-the transit time of microbubbles (source of the echo contrast
      effect) is inversely related to absolute flow, thus providing accurate
      quantitation. A similar situation is represented by blood flow inside a vessel or
      a cardiac cavity, where, if the prerequisites for quantitation are respected, it
      is possible to measure blood flow by contrast echocardiography. In the coronary
      circulation, the transit time of contrast microbubbles varies according to their
      interaction with coronary microcirculation, and to the characteristics of
      contrast agents as flow tracers. Echo contrast agents with small microbubbles
      have been injected into the coronary branches of experimental animals, under both
      coronary autoregulation and maximal coronary dilation, providing good estimates
      of coronary blood flow. The accuracy of these measurements might improve when new
      contrast agents, with characteristics closer to those of a flow tracer, are
      available. If a tracer is injected before a bifurcation, and provided it mixes
      adequately, the amount of tracer distributed to each branch is proportional to
      the corresponding blood flow. A similar situation is encountered when an echo
      contrast agent is injected into the aortic root or into the left main coronary
      artery. Here, the ratio between myocardial signal intensity in the different
      perfusion territories reflects the corresponding ratio of blood flows. The
      validity of this approach has been previously demonstrated in experimental
      animals and validated in patients with coronary stenoses. The injection of
      contrast agents into the coronary circulation at baseline and under coronary
      hyperaemia has the potential for measuring coronary blood flow reserve. However,
      what is still unclear is whether contrast echo changes reflect changes in
      coronary blood flow (i.e. flow reserve), coronary blood volume (i.e. coronary
      recruitment) or both, and also whether they influence the different types of
      contrast agent. Finally, myocardial contrast echocardiography can provide
      information on the spatial distribution of myocardial perfusion, i.e. the
      presence, site and extent of perfused myocardium. Thus, in models where
      myocardial perfusion may be either present or absent, contrast echo can provide
      an accurate estimate of perfusion abnormalities.

PMID- 8746938
TI  - Intravascular ultrasound imaging in patients with acute myocardial infarction.
AB  - Myocardial infarction is the result of acute thrombotic occlusion of a coronary
      artery secondary to rupture of an atherosclerotic plaque. Intracoronary
      ultrasonic examinations (ICUS) were performed in patients with acute myocardial
      infarction in order to describe intraluminal ultrasonic findings at the site of
      an acute coronary occlusion. Coronary angiography and ICUS studies were performed
      consecutively within 6 h after the onset of chest pain in 50 patients with acute
      myocardial infarction (AMI) prior to percutaneous coronary angioplasty (PTCA).
      Following angiographic documentation of a proximal occlusion, a 3.5 mechanical
      ultrasound catheter (30 MHz) was advanced successfully through the lesion in 42
      of 50 patients (84%). In 37 of the 42 patients (88.1%), ICUS differentiated
      between pulsatile, low echogenic, intraluminal material suggesting thrombus, and
      mural more highly echogenic atherosclerotic plaque. A negative imprint of the
      ICUS catheter was documented within the low echogenic material in 25 of 42 (60%)
      patients with AMI. Low echogenic intraluminal material was found in 31 of 42
      (73.4%) segments proximal to the highly echogenic plaque and in 28 of 42 (66.7%)
      segments distal to it, indicating pre- and post-stenotic thrombus in AMI. The
      plaque appeared eccentric in 32 of 42 patients (76.2%) with AMI. Cross-sectional
      area stenosis due to highly echogenic plaque averaged 48 +/- 14%. Calcification
      of plaque was evident in 35 of 42 patients (83.3%) and the surface of the plaque
      was rough in 30 of 42 (42.4%). Fissures were found in 10 (23.8%) and a dissection
      was detected in four (9.5%) cases.

PMID- 8746939
TI  - Principles of interpretation of coronary velocity and pressure tracings.
AB  - The development of quantitative angiography and the introduction of new
      techniques of intracoronary imaging cannot replace the functional methods for the
      assessment of stenosis severity. The measurement of the trans-stenotic pressure
      gradient and of the post-stenotic flow velocity using miniaturized sensors with
      guidewire technology offers an alternative to the conventional non-invasive
      methods which is applicable in the catheterization laboratory at the time of the
      interventional procedure. The complexity of the coronary circulation, however,
      limits the possibility of establishing simple cut-off criteria to identify the
      presence of a flow-limiting stenosis. For intermediate lesions, or in the
      presence of variable haemodynamic conditions, the accuracy of the assessment can
      be improved by the application of more complex indices, proposed and validated in
      the animal laboratory and based on the instantaneous relationship between
      pressure or pressure gradient and flow velocity.

PMID- 8746940
TI  - Changes of fluid-dynamic parameters in peripheral stenoses with transcutaneous
      interventions.
AB  - Peripheral vessels provide a useful in vivo haemodynamic model allowing
      evaluation of local intravascular fluid dynamics. Velocity measurements using a
      0.018 inch Doppler-tipped angioplasty guidewire, quantitative angiography and
      laboratory data were gathered from 45 patients with a total of 48 percutaneous
      transluminal laser assisted angioplasties (PTLA) in the superficial femoral, in
      the iliac, in the popliteal artery and in the peroneal artery. From these data,
      blood flow, whole blood viscosity, Reynold's numbers, Womersley numbers and shear
      stress were calculated, evaluated as to their changes post PTLA and correlated
      with clinical improvement at early follow-up. The clinical result was quantified
      as categorial improvement according to the American Heart Association guidelines.
      The primary angiographic results of angioplasty were satisfactory in all
      patients. Clinically 17/45 patients showed a marked, 6/45 a moderate, 18/45 a
      minimal, and 4/45 no improvement. The mean values of maximal peak velocity at
      stenosis decreased from 235 +/- 28 cms-1 to 84 +/- 8 cms-1 after PTLA (P < 0.01).
      The minimal intrastenotic cross section increased from 7.7 +/- 0.9 to 21.9 +/-
      1.6 mm2 (P < 0.01). Mean trans-stenotic flow increased after intervention by
      about 50% (P < 0.01) and improved further by 135% after administration of
      adenosine triphosphosphate i.a. (P < 0.01). Reynold's numbers were elevated
      intrastenotically (1285 +/- 198) pre-intervention as compared to values proximal
      (564 +/- 81) and distal (449 +/- 66) to the stenosis and were reduced
      significantly (P < 0.05) at stenosis by PTLA, whereas values proximally and
      distally increased significantly (P < 0.01) post PTLA (proximal 829 +/- 84, intra
      773 +/- 107, distal 676 +/- 98). Shear stress, reflecting mechanical interaction
      between flow and vessel wall, was elevated at stenosis pre-intervention to 44 +/-
      8.9 Pa and reduced at post-stenoric vessel sites to 2.4 +/- 0.5 Pa. PTLA caused a
      decrease in stenosis to 6.3 +/- 1 Pa (P < 0.01) and an increase distally to 4.6
      +/- 1 Pa (P < 0.01). Whereas in single stenoses removal of the obstruction was
      associated with a significant (P < 0.05) increase in trans-stenotic flow and
      shear stress distally, there was only auenuated increase in trans-stenotic flow
      in multiple lesions despite an angiographically good PTLA result. Shear stress
      distally remained low in those patients. Velocities and Reynold's numbers were
      lower in these vessels even pre PTLA. Residual flow, Reynold's number and minimal
      cross-section pre-intervention correlated significantly with clinical outcome.
      Pooling cases with no or minimal, as opposed to those with marked or moderate
      improvement, 81% of patients were correctly classified using the Reynold's
      numbers pre- and post-PTLA. CONCLUSION: Peak velocity monitoring is feasible and
      safe during angioplasty. Velocity provides clinically relevant physiological
      information in addition to angiography. Combining quantitative angiography,
      velocity measurements and laboratory data allow the calculation of blood flow,
      Reynold's numbers and shear stress, thereby providing complex fluid dynamic
      information. Thus the evaluation of haemo-dynamics in single and multiple
      obstructions before and after intervention is improved. Fluid dynamic parameters
      pre-and post-PTLA are significantly correlated with clinical short-term result.

PMID- 8746941
TI  - Coronary artery flow monitoring following coronary interventions.
AB  - Coronary guidewires with ultrasound transducer tips are commercially available
      and are appropriately sized for use in coronary interventions. These guidewires
      permit monitoring of coronary flow before, during and after the interventions.
      The measured flow signal contains valuable information regarding the quality and
      the stability of the final result. After completion of the procedure, monitoring
      the trend in average velocity over several minutes can reveal subtle alterations
      in flow that may presage abrupt closure. Abnormal or unstable flow patterns also
      may help predict lesions that might develop recurrences in the weeks and months
      after successful procedures.

PMID- 8746942
TI  - Quantification of collateral blood flow during PTCA by intravascular Doppler.
AB  - The assessment of flow velocity using the Doppler guidewire provides a means of
      investigating both antegrade and retrograde blood flow in the coronary artery
      distal to obstructive lesions and occluding PTCA balloons. This has yielded
      unique qualitative and quantitative information regarding coronary collateral
      blood flow, and the responses of collaterals to pharmacological and haemodynamic
      perturbations. The current study analysed collateral flow velocity recordings
      obtained during coronary interventions in 46 patients in our laboratory. The mean
      collateral peak velocity integral distal to the occluding PTCA balloon was 9 +/-
      7 units, while antegrade distal coronary peak velocity integral following
      stenosis relief by PTCA was 27 +/- 12 units. Thus, during PTCA balloon occlusion
      collaterals were able to supply a mean of 30 +/- 18% of the flow provided
      antegrade by successful PTCA. Variability in collateral flow velocity was not
      accounted for by differences in the PTCA artery assessed, the supply artery, the
      direction of collateral filling, the severity of coronary stenosis, or the
      angiographic grade of collaterals, and the magnitude of collateral flow velocity
      did not correlate with preserved left ventricular regional wall motion. The
      measurement of collateral flow velocity by intravascular Doppler provides unique
      and quantitative information regarding the coronary collateral circulation.

PMID- 8746943
TI  - Endothelial dysfunction in heart transplanted patients with graft vasculopathy.
AB  - The pathological mechanism of cardiac transplant vasculopathy (TVP) is uncertain.
      We tested the hypothesis that the endothelial function, in terms of the release
      of endothelium-derived relaxing factor, is impaired in patients with angiographic
      evidence of transplant vasculopathy. In a pilot study, the effects of the
      substances used (substance P, acetylcholine, nitroglycerin) were assessed as
      regards tone of pre-contracted human coronary arteries in vitro, obtained from
      recipient hearts during cardiac transplantation. The study shows that substance P
      is a "pure' endothelium-dependent dilator of epicardial human coronary arteries,
      whereas acetylcholine has a more complex effect on vascular tone involving both a
      direct effect on the endothelium and the smooth muscle cells. In a second pilot
      study, the effects of intracoronary infusions of substance P (5-100 pmol.min-1)
      and acetylcholine (2-50 nmol.min-1) on flow velocity were compared in 10 patients
      undergoing cardiac catherization after heart transplantation. Flow velocity was
      determined by a 3F Doppler catheter placed into the proximal segment of the left
      anterior descending artery (LAD). Both drugs increased concentration-dependent
      flow velocity; substance P and acetylcholine maximally increased flow velocity by
      about 85 +/- 24% and 143 +/- 15%, respectively (P < 0.05). In a third study, 23
      patients undergoing diagnostic cardiac catheterization were included
      approximately 40 months after heart transplantation. Patients were classified
      into those with (n = 8) and those without (n = 15) angiographic evidence of TVP.
      Coronary flow velocity (by Doppler) and epicardial coronary diameter (by
      quantitative angiography) were determined after intracoronary injections of
      substance P (20 pmol), nitroglycerin (0.1 mg), and papaverine (8 mg). Substances
      were injected through the central lumen which was placed into the LAD. Increases
      in flow velocity in response to substance P were significantly less in patients
      with TVP than in patients without evidence of TVP. Moreover, flow-mediated
      vasodilation in response to papaverine was almost abolished in patients with TVP.
      Vasodilation in response to nitroglycerin and maximal increase in flow velocity
      in response to papaverine was similar in both groups. These results suggest that
      TVP is associated with endothelial dysfunction, which may contribute to the
      pathogenesis of TVP and its vascular complications.

PMID- 8746944
TI  - Quantification of regional myocardial perfusion by PET: rationale and first
      clinical results.
AB  - With the recent advances in interventional cardiology there is increasing need
      for characterization of the functional effects of coronary artery stenosis.
      Stress echocardiography and SPECT perfusion imaging are standard techniques for
      the qualitative assessment of regional function and perfusion in patients with
      proven or suspected coronary artery disease. However, Positron emission
      tomography (PET) provides quantitative measurements of regional myocardial
      perfusion. In combination with pharmacological stress testing, relative and
      absolute coronary reserve measurements can be used to define functional
      significance of regional coronary artery disease. First clinical results indicate
      that there is an overall agreement between angiographic and functional disease
      severity. However, there is a relatively large scatter of coronary reserve flow
      in patients with 50-90% coronary artery stenosis, which emphasizes the
      complimentary role of perfusion imaging in the prediction of functional severity.
      In addition, first studies in asymptomatic patients with a high risk for coronary
      artery disease suggest that PET coronary reserve flow measurement may be more
      sensitive than angiographic criteria for detection of early alterations in
      coronary vascular reactivity. Absolute quantification of blood flow may be useful
      in disease processes which affect the entire left ventricle such as vasculopathy
      in cardiac transplants, as well as endothelial dysfunction in patients with
      hypertension and cardiomyopathy. Future studies have to demonstrate the
      prognostic value of the quantitative estimate of coronary reserve as regards
      clinical outcome in patients with various coronary abnormalities. Quantitative
      flow measurements will be useful for monitoring progression and regression of
      coronary artery disease as well as assessment of acute and chronic therapy.

PMID- 8746945
TI  - The plasma membrane calcium pump--a physiological perspective on its regulation.
AB  - This review focuses on the physiological role of the plasma membrane Ca(2+)+
      Mg(2+)-dependent adenosine triphosphatase (PM Ca(2+)-ATPase) in cellular
      signalling. Particular attention has been paid to the regulation of the PM Ca(2+)
      ATPase (PM Ca2+ pump) by calmodulin, proteases, protein kinases, acidic
      phospholipids and oligomerization in intact cells. We also review recent work
      investigating the possible regulation of the PM Ca2+ pump by G proteins and
      agonists. The source of adenosine triphosphate (ATP) and Ca2+ in fueling and
      activating the Ca2+ pump is discussed, as well as the possible role of the PM
      Ca(2+)-ATPase in subplasma membrane Ca2+ regulation. The physiological
      implication of the localisation of the PM Ca2+ pump in caveolae is also
      considered.

PMID- 8746946
TI  - Protein kinase C activation inhibits receptor-evoked inositol trisphosphate
      formation and induction of cytosolic calcium oscillations by decreasing the
      affinity-state of the cholecystokinin receptor in pancreatic acinar cells.
AB  - Digital-imaging microscopy of Fura-2-loaded pancreatic acinar cells revealed that
      the C-terminal octapeptide of cholecystokinin (CCK8) dose-dependently recruited
      94% of freshly isolated acinar cells in terms of receptor-evoked Ca2+
      mobilization. Maximal and half-maximal cell-recruitment were reached with 0.1 nM
      and 16.8 pM CCK8, respectively. The upstroke of the dose-recruitment curve
      consisted of cells displaying oscillatory changes in free cytosolic Ca2+
      concentration ([Ca2+]i). After having reached its maximum, the percentage
      oscillating cells dose-dependently decreased upon further increasing of the CCK8
      concentration. Pretreatment of the acinar cells with 0.1 microM TPA caused a
      rightward shift of the dose-recruitment curve but did not change the maximal
      effect of CCK8 on the recruitment of oscillating cells. Half-maximal recruitment
      was obtained with 287 pM CCK8. This observation demonstrates that high levels of
      protein kinase C activation do not inhibit Ca2+ oscillations at a level
      downstream to receptor activation. Moreover, this observation demonstrates that
      protein kinase C-mediated inhibition of Ca2+ oscillations evoked by submaximal
      CCK8 concentrations occurs at the receptor level, converting it from a high
      affinity state into a low-affinity state. This conclusion is supported by the
      observation that TPA completely inhibited the recruitment of acinar cells in
      response to the high-affinity receptor agonist JMV-180. The inhibitory action of
      TPA on CCK8-evoked cell-recruitment was paralleled by an inhibitory effect of the
      phorbol ester on the CCK8-evoked peak increase in average inositol trisphosphate
      concentration in a population of acinar cells. This observation indicates that
      low concentrations of CCK8 interact with the high-affinity CCK receptor to
      increase [Ca2+]i through the intermediation of inositol trisphosphate.

PMID- 8746947
TI  - Fluorometric measurement of the intracellular free Ca(2+)-concentration in the
      ciliate Didinium nasutum using Fura-2.
AB  - We developed an experimental approach to measure somatic and ciliary Ca(2+)
      signals in the ciliate Didinium under voltage clamp conditions using the dye Fura
      2. Intracellular pressure injection of Fura-2 molecules did not alter
      electrophysiological membrane properties besides an expected buffering effect.
      The intracellular free Ca(2+)-concentration was determined at 2 x 10(-7) M.
      During membrane excitation, this resting value increased in the cilia; a
      quantification was not feasible. Within the cell soma, however, the Ca(2+)-level
      was unchanged within the physiological range of the membrane potential (-70 mV to
      0 mV). Increasing the driving force for Ca(2+)-ions via strong hyperpolarization
      (potentials negative to -200 mV) a centripetal increase in the somatic Ca2+
      concentration was found. Our results support the hypothesis that Ca2+ is the
      intracellular messenger in rapid electromotor coupling in ciliates.

PMID- 8746948
TI  - Hepatocyte growth factor-induced calcium waves in hepatocytes as revealed with
      rapid scanning confocal microscopy.
AB  - Cytosolic Ca2+ transients induced by hepatocyte growth factor (HGF) were imaged
      in primary cultured rat hepatocytes using newly developed rapid scanning confocal
      microscopes and indo-1. HGF (40 ng/ml) increased cytosolic free Ca2+
      concentration ([Ca2+]i) in about 60% of hepatocytes, in 45% of which the
      increases were oscillatory. In each of the oscillatory hepatocytes, the
      repetitive increases in [Ca2+]i originated from a specific same region adjacent
      to the cell membrane and propagated across the cell like waves. Phenylephrine (10
      microM) also induced Ca2+ waves. The locus where HGF-induced Ca2+ waves and
      phenylephrine-induced Ca2+ waves were originated was the same, and there was a
      correlation in the peak height between HGF-induced Ca2+ waves and phenylephrine
      induced Ca2+ waves in each cell, although the mechanisms of inositol 1,4,5
      trisphosphate (ins(1,4,5)P3) formation induced by HGF should be different from
      those by phenylephrine. On the other hand, there was no correlation between
      sensitivity of each cell to HGF and that to phenylephrine which were measured as
      latent periods prior to Ca2+ rises after an addition of the agonists. These
      results suggested the following: the spatial patterns of Ca2+ waves were decided
      by a common mechanism, probably not the propagation of ins(1,4,5)P3 but the
      distribution of ins(1,4,5)P3-sensitive Ca2+ pools; sensitivities of each cell to
      the agonists did not mainly depend on the common mechanism.

PMID- 8746949
TI  - Activation of voltage-independent Ca2+ entry by noradrenaline involves cGMP in
      vascular myocytes.
AB  - Stimulation of portal vein myocytes with noradrenaline (NA) in the presence of a
      voltage-dependent Ca2+ channel blocker, evoked a transient increase in the
      concentration of free cytosolic Ca2+, due to inositol 1,4,5-trisphosphate
      mediated Ca2+ release, followed by activation of a Ca2+ entry pathway. Combining
      patch-clamp and indo-1 measurements we have tested the effects of various
      pharmacological agents on this Ca2+ entry following NA-induced Ca2+ release in
      order to determine the mechanism involved. Only the guanylate cyclase inhibitor
      LY-83583 specifically inhibited the maintained Ca2+ entry during NA stimulation.
      This inhibition was reversed by dibutyryl cGMP (DB-cGMP) or 8-bromo cGMP. Under
      control conditions, addition of DB-cGMP to the external solution was without
      effect. Thapsigargin and caffeine each depleted the intracellular Ca2+ store but
      did not evoke Ca2+ entry in venous myocytes under control conditions. However,
      application of DB-cGMP or NA after Ca2+ store depletion induced by caffeine or
      thapsigargin caused a rise in [Ca2+]i by activation of a Ca2+ entry pathway. The
      effect of cGMP seems to involve phosphorylation since cGMP-activated protein
      kinase inhibitors KT-5823 and H-8 blocked the NA-induced Ca2+ entry. Our results
      thus suggest that the activation of the voltage-independent Ca2+ entry by NA
      involves an increase in cellular cGMP.

PMID- 8746950
TI  - Alpha-adrenergic agonist and endothelin-1 induced intracellular Ca2+ response in
      the presence of a Ca2+ entry blocker in cultured rat ventricular myocytes.
AB  - Previously we demonstrated that stimulation of cultured neonatal rat ventricular
      myocytes by either alpha 1-adrenergic agonist or endothelin-1 resulted in a rapid
      formation of total inositolphosphates, although the levels of inositol 1,4,5
      trisphosphate and inositol 1,3,4,5-tetrakisphosphate did not rise significantly.
      The aim of this study was to examine whether stimulation by alpha 1-adrenergic
      agonist and endothelin-1 could still elicit phosphatidylinositol cycle mediated
      intracellular Ca2+ mobilization in these cells. The intracellular free Ca2+
      concentration ([Ca2+]i) was measured by single cell imaging dual wavelength
      fluorescence microscopy in Fura-2-loaded cardiomyocytes. The interference of
      agonist induced [Ca2+]i responses by the beat to beat variation of [Ca2+]i was
      prevented by arresting the cells with the Ca2+ entry blocker diltiazem (10
      microM). The [Ca2+]i response (expressed as % of baseline ratio of fluorescence
      intensities of Fura-2 at 340 nm and 380 nm excitation wavelength), induced by
      phenylephrine (10(-4) M) and endothelin-1 (10(-8) M) was small, up to 20% of
      baseline after 9-20 min. In contrast, Ca(2+)-influx induced by incubation in
      Na(+)-free buffer caused a steep increase of [Ca2+]i up to 150% of baseline after
      30 s. Analysis of single cells following stimulation with phenylephrine or
      endothelin-1 showed heterogeneity with respect to a rise in [Ca2+]i. However, if
      rapid Ca(2+)-influx was induced by incubation in Na(+)-free buffer, [Ca2+]i
      responses in individual myocytes occurred homogeneously. It is concluded that the
      alpha 1-adrenergic agonist and endothelin-1 induced [Ca2+]i responses are delayed
      in time, small and quite heterogeneous among cells. The findings are in agreement
      with earlier observations which revealed no detectable overall increase of the
      Ca2+ releasing inositolphosphates under these conditions and suggest that other
      second messengers, such as 1,2-diacylglycerol, are involved in the agonist
      mediated Ca2+ signals.

PMID- 8746951
TI  - Protein kinase C modulates cytosolic free calcium by stimulating calcium pump
      activity in Jurkat T cells.
AB  - Although protein kinase C (PKC) activation has been shown to inhibit Ca2+ influx
      in T lymphocytes, the role of PKC on Ca2+ sequestration or extrusion processes
      has not been fully explored. We examined the effect of CD3 stimulation and PKC
      activators on cytosolic Ca2+ (Ca2+i) extrusion and 45Ca2+ efflux in human
      leukemic Jurkat T cells. Treatment of Fura-2 loaded cells with phorbol 12
      myristate 13-acetate (PMA) or thymeleatoxin (THYM) resulted in a decrease in
      Ca2+i both in the presence and absence of extracellular Ca2+, whereas inactive
      phorbol esters had no effect. PKC activators added at the peak of a Ca2+i
      transient induced by anti-CD3 mAb, ionomycin or thapsigargin (TG) stimulated the
      rate and extent of return of Ca2+i to basal levels by 17-53%. PKC stimulation of
      the Ca2+i decline was not enhanced by the presence of Na+, indicating that PKC
      activators increase Ca2+ pump activity rather than a Na+/Ca2+ exchange mechanism.
      As CD3 receptor activation enhanced the Ca2+i decline in TG-treated cells,
      antigen-mediated activation of phospholipase C (PLC) signaling includes enhanced
      Ca2+ extrusion at the plasma membrane. The effect of PKC activators on parameters
      of Ca2+i extrusion were further explored. PMA significantly increased the rate of
      Ca2+ extrusion in TG-treated cells from 0.28 +/- 0.02 to 0.35 +/- 0.03 s-1 (mean
      +/- SEM) and stimulated the initial rate of 45Ca2+ efflux by 69% compared to
      inactive phorbol ester treated cells. The effects of PKC activation on the Ca2+i
      decline were eliminated by PKC inhibitors, PKC down regulation (24 h PMA
      pretreatment), ATP-depletion and conditions that inhibited the Ca2+ pump. In
      contrast, pretreatment of cells with okadaic acid enhanced the PMA-stimulated
      response. We suggest that Jurkat T cells contain a PKC-sensitive Ca2+ extrusion
      mechanism likely to be the Ca2+ pump. In lymphocytes, receptor/PLC-linked PKC
      activation modulates Ca2+i not only by inhibiting Ca2+ influx but also by
      stimulating plasma membrane Ca2+i extrusion.

PMID- 8746952
TI  - Role of mitogen-induced calcium influx in the control of the cell cycle in Balb-c
      3T3 fibroblasts.
AB  - The role of mitogen-activated calcium influx from the extracellular medium in the
      control of cell proliferation was studied in Balb-c 3T3 fibroblasts. Stimulation
      of serum-deprived, quiescent cells with 10% foetal calf serum (FCS) induced a
      long-lasting (up to 70 min) elevation of intracellular free calcium concentration
      ([Ca2+]i). Both the sustained [Ca2+]i increase and the related inward current,
      described in a previous paper [Lovisolo D. Munaron L. Baccino FM. Bonelli G.
      (1992) Potassium and calcium currents activated by foetal calf serum in Balb-c
      3T3 fibroblasts. Biochim. Biophys. Acta, 1104, 73-82], could be abolished either
      by chelation of extracellular calcium with EGTA or by SK&F 96365, an imidazole
      derivative that can block receptor-activated calcium channels. The effect of the
      abolition of these ionic signals on FCS-induced proliferation was investigated by
      adding either EGTA or SK&F 96365 to the culture medium during the first hours of
      stimulation of quiescent cells with 10% FCS. As measured after 24 h, a 22%
      inhibition of growth was observed when SK&F 96365 was added for the first hour,
      and stronger inhibitions, up to 56%, were obtained by adding the blocker for the
      first 2 or 4 h. Similar effects were observed with addition of 3 mM EGTA, though
      the inhibition was less marked for the 4 h treatment. By contrast, incubation
      with either substance in the next 4 h of serum stimulation did not influence cell
      growth, except for a slight inhibition observed when SK&F 96365 was applied from
      the 4th to the 8th hour. The reduction in growth resulting from the abolition of
      the early calcium influx was paralleled by an accumulation of cells in the G2/M
      phase. Both growth inhibition and G2/M accumulation were reversible, since after
      further 24 h in 10% FCS cells had fully recovered the exponential growth. These
      data indicate that the early calcium influx seen in response to mitogen
      stimulation develops on a timescale long enough to play a significant role in
      cell cycle progression, and that its block in the early G1 phase can lead to a
      reduction of proliferation by arresting cells in later stages of the cycle.

PMID- 8746954
TI  - Detection of proliferating cell nuclear antigen (PCNA) in canine and feline
      mammary tumours.
AB  - Quantitation of immunohistochemical staining of the proliferating cell nuclear
      antigen (PCNA, clone PC10) by image analysis was performed on benign and
      malignant mammary tumours of dogs and cats. Scoring of the slides was carried out
      by image analysis to assess the percentage of labelled nuclei (expressed as a
      ratio of areas). Either the strongly labelled nuclei (SP-PCNA index), or all of
      the stained nuclei (TP-PCNA index) were counted as positive to determine the
      growth fraction and its correlation with the histopathological classification and
      nuclear grade (degree of nuclear differentiation, considered a morphological
      correlate of tumour aggressiveness). A significant difference in the values of
      PCNA indices was seen between benign and malignant growths (P < 0.0001, dog; P <
      0.05, cat). Neither of the PCNA indices showed correlation with nuclear grade in
      dogs (P = 0.14 for SP-PCNA index and P = 0.31 for TP-PCNA index) or cats (P =
      0.09 for SP-PCNA index and P = 0.07 for TP-PCNA index). A significant difference
      in the number of mitoses, expressed as mitotic index, was seen between benign and
      malignant growths in the dog (P < 0.01) but not in the cat (P = 0.078). Good
      correlation of mitotic index with nuclear grade was revealed in canine malignant
      growths (P < 0.05), but in feline malignant tumours such correlation (P < 0.05)
      was shown only when the values of intermediate plus typical forms were compared
      with the data for atypical forms. It is concluded that quantitation of PCNA
      positive nuclear area by image analysis provides an objective method for
      assessing proliferative activity in benign and malignant mammary tumours of dogs
      and cats.

PMID- 8746953
TI  - Binding of ADP to sarcoplasmic reticulum Ca(2+)-ATPase in the absence of Mg2+ is
      specifically inhibited by thapsigargin: observations on the ligand stoichiometry.
AB  - The conditions of nucleotide binding to native, though partly purified, Ca(2+)
      ATPase from SR as well as the stoichiometry of nucleotide and strontium binding
      and the phosphorylation capacity was reevaluated. Binding of MgADP appeared to be
      aberrant whereas even high-affinity binding of [14C]-ADP took place in the
      absence of Mg2+. Also low-affinity ATP binding was possible in the absence of
      divalent cations. A heterogeneity in ADP binding compatible with a two-component
      model in the absence of thapsigargin was changed to an apparent homogeneity of
      low-affinity receptors following a mole:mole interaction of enzyme and
      thapsigargin. Since the affinity of both components was reduced by thapsigargin,
      high- as well as low-affinity ADP binding seem to be specific and probably to the
      substrate receptor proper. Analysis of ADP binding isotherms in the absence of
      Mg2+ according to a model of two independent populations of sites was compatible
      with a binding capacity of 8.49 +/- 0.43 nmoles/mg protein corresponding to a
      molecular mass of 118 +/- 6 kD per ADP site. The same total binding capacity was
      found for ATP. The phosphorylation capacity corresponded to more than one and
      less than two approximately P per two 110-kD peptides (formally one approximately
      P per 154 kD protein). Specific binding of Ca2+ and the congener Sr2+ to SR
      Ca(2+)-ATPase was compatible with their interaction with a single population of
      sites. The binding capacity was equal to one divalent cation per nucleotide
      binding peptide. The binding of one nucleotide and one divalent cation per
      approximately 110 kD peptide and the absence of cooperativity in divalent cation
      binding might imply that Ca(2+)-ATPase works as a monomer.

PMID- 8746955
TI  - A murine model for the study of mycotic mastitis.
AB  - This study established a murine model for the study of mycotic mastitis. The
      mammary glands of BALB/c mice were inoculated on the fifth day of lactation with
      graded doses (10(4), 10(5) and 10(6) cells) of a pathogenic strain of Candida
      krusei isolated from bovine mastitis. The animals were killed 1, 2, 3, 4 or 5
      days after inoculation. In the infected mammary glands, the pathological reaction
      consisted of primary infiltration with heterophils and mononuclear cells, focal
      necrosis, formation of microabscesses, epithelial hyperplasia and some fibrosis.
      The severity of the changes was dose-dependent and increased with time after
      infection. An increase in the plasma concentrations of complement factors C1,
      C3c, C4 and C5, factor B and alpha-2-macroglobulin suggested that an acute phase
      response and activation of the complement system had occurred as a result of the
      infection.

PMID- 8746956
TI  - Progression of canine mammary tumours as reflected by DNA ploidy in primary
      tumours and their metastases.
AB  - Thirty dogs with metastasizing mammary tumours (carcinomas, n = 22; sarcomas, n =
      8) were necropsied. Flow cytometric DNA analysis was carried out on frozen
      primary tumours and on selected metastases from the dogs. Ductular carcinomas (n
      = 13) had a varying growth pattern, in terms of histology, in both the primary
      tumours and metastases and between different metastases. The different types of
      DNA ploidy, including hypodiploidy, in the primary ductular carcinomas were also
      seen in the tumour metastases. Dogs with primary anaplastic carcinomas (n = 7)
      had multiple metastases, which were in most cases near-diploid or hyperdiploid.
      Two dogs had spindle-cell carcinomas, which were hypodiploid in both the primary
      tumour and the metastases. The DNA ploidy in the metastases was retained in 16 of
      the 22 dogs with primary carcinomas. Fibrosarcomas (n = 5) showed different types
      of DNA ploidy. In two of the three dogs with diploid or near-diploid
      osteosarcomas, the DNA ploidy was retained in the metastases. There was a
      statistically significant association between mammary tumours and metastases (P =
      0.0001) in terms of both histological diagnosis and DNA ploidy. The association
      was retained when the carcinomas were tested separately (P = 0.0001); in the
      sarcomas it was retained weakly in terms of histology (P = 0.0183) but not DNA
      ploidy (P = 0.6659). The retention of the DNA ploidy in most carcinoma metastases
      indicated that selection of DNA ploidy had taken place prior to metastasis. The
      differences in patterns of DNA ploidy between ductular and anaplastic carcinomas
      may reflect different pathogenesis in these types of canine mammary tumour.

PMID- 8746957
TI  - Rise in erythropoietin concentrations in experimental Trypanosoma congolense
      infection of calves.
AB  - A bioassay was used to measure erythropoietin (EPO) concentrations in calves with
      haemorrhagic anaemia due to blood loss and in calves with anaemia due to
      Trypanosoma congolense infection. The bioactivity of EPO was measured in the
      assay by its stimulatory effect on 125I-deoxyuridine incorporation in spleen
      cells from phenylhydrazine-treated mice. Erythropoietin concentrations in blood
      volume-depleted calves were elevated 6 h after blood loss, maximal (1225 mU/ml)
      at 33 h and below detection limits at 72 h. Reticulocytes (0.05 +/- 0.1%)
      appeared in blood by 72 h, peaked at 120 h and disappeared from the circulation
      by 7 days after bleeding. The packed cell volume (PCV) started increasing at 120
      h and reached near pre-bleeding values by 14 days. In T. congolense-infected
      calves, parasites were first detected in the peripheral blood 12 days post
      infection (dpi). Parasitaemia peaked (5 x 10(5) trypanosomes/ml of blood) at 15
      18 dpi and, thereafter, several waves of parasitaemia were observed, but the
      peaks gradually diminished. Undiluted plasma from T. congolense-infected calves
      suppressed 125I-deoxyuridine incorporation into spleen cells from 13 dpi onwards.
      The suppressive effect of plasma was partly negated by five-fold dilution, which
      made possible the detection of increased EPO concentrations during the acute and
      chronic stages of the anaemia. The highest EPO peaks, reaching 2300 mU/ml in one
      calf, were detected during the chronic stage of the infection. At 15-39 dpi,
      there was a transient bone-marrow erythropoietic response characterized by an
      increase in mean corpuscular volume and a decrease in mean corpuscular
      haemoglobin concentration but with few reticulocytes (0.4%). However, from 76 dpi
      onwards, this response waned despite low PCV and elevated EPO concentrations.
      These results suggest that there is an ineffective erythroid response in the face
      of elevated EPO concentrations during bovine trypanosomiasis. The negative effect
      of plasma and serum from trypanosome-infected calves on the in-vitro bioactivity
      of EPO suggests the presence of inhibitory factors.

PMID- 8746958
TI  - Spongiform central nervous system myelinopathy in African dwarf goats.
AB  - A novel spongiform myelinopathy of the central nervous system (CNS) of eleven
      African dwarf goats was examined by light and electron microscopy. Histological
      lesions consisted of extensive vacuolation predominantly of the white matter of
      the diencephalon, midbrain and cerebellar peduncles, as well as of spinal white
      matter. Ultrastructurally, vacuoles were shown to be intramyelinic, resulting
      from the splitting of the outer myelin lamellae at the intraperiod line. A few
      oligodendrocytes showed vacuolar degeneration of cell bodies and processes.
      Inflammatory reactions were absent. The observed lesions point to an unknown
      primary damage of oligodendroglia and central myelin. A hereditary background of
      the disorder is suspected as all investigated dwarf goats were half-brothers or 
      sisters and partly descended from the mating of adult females with their own
      sire.

PMID- 8746959
TI  - Peripartum heart disease in cows.
AB  - Thirteen Holstein dairy cows aged 5.1-10.6 years died or were killed as a result
      of severe illness during the peripartum period, associated with lateral
      recumbency, moaning, tachycardia and dyspnoea. They were all high milk producers
      (> 9000 kg/year) and had experienced at least three pregnancies. The average
      duration of the clinical course was 2.5 +/- 1.7 days. Electro-cardiography
      revealed marked tachycardia associated with atrial fibrillation or
      atrioventricular dissociation. Serum clinical chemistry showed severe
      hypocalcaemia (3.6 +/- 1.3 mg/dl) and at necropsy multifocal myocardial necrosis
      was invariably found. Myocardial necrosis was accompanied by neutrophilic and
      mononuclear cellular infiltrates with interstitial fibrosis. The cause of this
      lesion was not established.

PMID- 8746960
TI  - Transplantation of a cell line derived from a canine benign mixed mammary tumour
      into nude mice.
AB  - The MCM-B2 canine mammary cell line was serially transplanted into nude mice. The
      tumour masses consisted of elongated pleomorphic cells of varying size in the
      first to third passages; oval cells, becoming rounder, in the sixth to eighth
      passages; and cord-like, glandular and duct-like structures with compact
      radiating projections in the ninth and tenth passages. Ultrastructural and
      immunohistochemical examination of round cells confirmed their epithelial cell
      nature, but the morphology of the elongated and oval cells was identical with
      that of the original cell line. The findings suggest that the MCM-B2 cell line is
      a multipotential stem cell or is derived from glandular differentiation of
      mammary gland.

PMID- 8746961
TI  - Family resemblance in beliefs, attitudes and intentions towards consumption of 20
      foods; a study among three generations of women.
AB  - Family resemblance in beliefs, attitudes and intentions towards the consumption
      of 20 foods that contribute to the fat intake was investigated in 97 adult women,
      their mothers and their grandmothers. Mean correlation for elements from the
      Fishbein and Ajzen theory of reasoned action between younger and middle
      generations ranged from 0.09 to 0.17 and between middle and older generations
      from 0.12 to 0.17. All significant correlations were positive. More statistically
      significant correlations were found for liking attitudes between the younger and
      middle generations (p < 0.05 for ten out of 20 correlations) than for other
      pairs. Between the older and younger generation the number of significant
      correlations could be due to chance alone. From the relative importance of liking
      and good/bad attitude on intention it appeared that liking contributed the most
      to the variance in intention scores. Health related beliefs and attitudes became
      of increasing importance in the older generations. From this study it can be
      concluded that mothers and their adult daughters resemble each other in beliefs,
      food preferences, attitudes and intentions, although resemblance is poor.

PMID- 8746962
TI  - Use of reduced-calorie/reduced-fat foods by young adults: influence of gender and
      restraint.
AB  - Reduced-calorie/reduced-fat (RC/RF) foods are widespread in the food supply, but
      there are few published data on who is using them and why. A total of 226 college
      men (n = 76) and women (n = 150) participated in a survey investigating the
      influence of gender and dietary restraint on eating habits, dieting and the use
      of 11 categories of RC/RF foods. Men did not differ from women in their overall
      use of RC/RF foods, although specific foods were consumed by a greater percentage
      of women. Restrained eating was strongly related to use of all the foods (p < or
      = 0.001). Women and those higher in restraint used the foods primarily for weight
      control purposes, whereas men and those lower in restraint tended to use the
      foods for both weight control and other reasons. Women and those high in
      restraint were also more likely to have changed their eating habits to achieve
      weight loss and maintenance goals and to achieve a healthier lifestyle. In
      contrast, a greater percentage of men and those low in restraint wanted to
      achieve weight gain. These data suggest that RC/RF foods were popular among
      respondents in the study, but that the reasons for their use by restrained and
      unrestrained eaters might reflect gender differences in body weight and health
      concerns.

PMID- 8746963
TI  - Morning sickness: impact on offspring salt preference.
AB  - These studies examined the relationship between salt preference of adult
      offspring and their mothers' symptoms of morning sickness during pregnancy.
      College students who could provide information about their mothers' symptoms of
      morning sickness completed a survey about their dietary salt intake (study 1; n =
      169) or rated and consumed ten snack foods (study 2; n = 66). In study 1 a salt
      use score was calculated based on responses to the Salt Intake Questionnaire;
      offspring of women with moderate or severe vomiting reported a significantly
      higher level of salt use (p < 0.01) than those whose mothers report little or no
      symptoms. In study 2 saltiness and pleasantness ratings of high-salt foods,
      intake of those foods and total sodium intake were the focus of analysis.
      Offspring of women reporting moderate or severe vomiting showed a significantly
      greater preference for the snack food subjects rated as saltiest than those whose
      mothers reported no or mild vomiting. They also ate more of that food and
      consumed more total sodium during the test session. Effects were stronger in
      Caucasian than Asian subjects. These studies suggest that moderate to severe
      vomiting during pregnancy can be associated with significantly higher salt intake
      in offspring. Thus, a gestational event may be an important determinant of salt
      intake and preference in adulthood.

PMID- 8746964
TI  - Nutritional implications of reduced-fat food use by free-living consumers.
AB  - The nutritional implications of the purchase and consumption of reduced-fat foods
      at home were assessed in normal-weight, free-living consumers in a 6-week
      intervention study. Control (n = 14) and experimental (n = 15) subjects kept 4
      day weighed food diaries to establish energy and macronutrient intake at baseline
      and experimental weeks 2, 4 and 6. The control group continued their habitual
      diet throughout the study whereas the experimental group used reduced-fat foods
      ad libitum in place of the traditionally high-fat counterparts that they usually
      consumed. All subjects purchased the majority of their groceries from the same
      food store and were reimbursed for a proportion of their grocery bill. Repeated
      measures analysis of variance indicated that the experimental group, compared to
      the control group, significantly reduced their percentage of energy from fat
      (from 38.3 +/- 1.8 to 30.4 +/- 1.7), but increased the percentage of energy from
      protein (p = 0.06) and carbohydrate (p = 0.019) such that changes in total energy
      intake were not statistically significantly different between conditions.
      Nevertheless, the experimental group lost 1.1 kg (while the control group gained
      0.4 kg) in the first 4 weeks of the study, consistent with the observed reduction
      in energy intake, though no further body weight changes were seen in week 6. This
      study suggests that although use of reduced-fat foods may have short-term effects
      on energy balance, long-term sustained reduction in energy intake may be limited
      if this dietary strategy is used in isolation.

PMID- 8746965
TI  - Shift related dietary intake in day and shift workers.
AB  - To study the impact of work hours on eating habits the dietary intake of 96 male
      industrial workers on day work and two- and three-shift work was investigated
      using repeated 24 h recall. The intake of energy, 14 nutrients, and coffee and
      tea was computed, using a nutrient data base, for 8 h work and shifts (day,
      morning, afternoon, night) and for the 24-h periods including these work shifts.
      No changes in intake of energy, nutrients and coffee/tea were observed between 8
      h morning and afternoon shifts, but there was a reduction in intake during 8 h
      night shifts. Night shift work caused a redistribution of food and coffee intake,
      but not an overall 24 h reduction. On the whole, the energy-intake and the
      quality of food intake (percentages of energy from macronutrients and density of
      micronutrients) were not affected by shift work, although the intake of
      carbohydrates was lower in day- and three-shift workers during days off. The
      intake of alcohol was higher during days off in all groups. In summary, two- and
      three-shift work in this study affected the circadian distribution of food
      intakes and coffee consumption, but not the overall 24-h consumption.

PMID- 8746966
TI  - Development of a measure of the motives underlying the selection of food: the
      food choice questionnaire.
AB  - A number of factors are thought to influence people's dietary choices, including
      health, cost, convenience and taste, but there are no measures that address
      health-related and non-health-related factors in a systematic fashion. This paper
      describes the development of a multidimensional measure of motives related to
      food choice. The Food Choice Questionnaire (FCQ) was developed through factor
      analysis of responses from a sample of 358 adults ranging in age from 18 to 87
      years. Nine factors emerged, and were labelled health, mood, convenience, sensory
      appeal, natural content, price, weight control, familiarity and ethical concern.
      The questionnaire structure was verified using confirmatory factor analysis in a
      second sample (n = 358), and test-retest reliability over a 2- to 3-week period
      was satisfactory. Convergent validity was investigated by testing associations
      between FCQ scales and measures of dietary restraint, eating style, the value of
      health, health locus of control and personality factors. Differences in motives
      for food choice associated with sex, age and income were found. The potential
      uses of this measure in health psychology and other areas are discussed.

PMID- 8746967
TI  - Psychosocial determinants of fruit and vegetable consumption.
AB  - Psychosocial correlates of fruit and vegetable consumption were studied in an
      adult Dutch population (n = 367) based on the ASE model of attitudes, social
      influence and self-efficacy. Attitudes were a summation of beliefs about taste,
      different health consequences, and costs in time and money. Social influences
      were measured through the social stimulation respondents expected to get from
      important others to consume adequate amounts of fruit and vegetables and by
      asking the subjects about the behaviour of important others. Self-efficacy
      reflected the respondents' ability to consume adequate amounts of fruit and
      vegetables in various situations. Self-efficacy and attitudes were consistently
      and significantly associated with consumption of boiled or otherwise heated
      vegetables, of salads, and of fruit. Furthermore, respondents reporting low
      consumption of these food groups had lower self-efficacy expectations and less
      positive attitudes than subjects with relatively high consumption of fruit and
      vegetables. It is concluded that nutrition education aimed at stimulating fruit
      and vegetable consumption should focus especially on changing attitudes and self
      efficacy expectations.

PMID- 8746968
TI  - Lunchtime food consumption of preschool children over a 2-year period.

PMID- 8746969
TI  - Intestinal factors in fat-induced satiety in animals and humans.

PMID- 8746970
TI  - Inhibition of eating in humans: assessment, mechanisms, and disturbances.

PMID- 8746971
TI  - Examination of egg number and egg weight variables and their effects on daily
      management in aviary systems for laying hens.
AB  - 1. Characteristics of egg numbers and mean egg weight were examined for their
      usefulness in the daily management of aviary systems for laying hens. 2. A number
      of 3238 brown Isabrown/Warren hens were housed in 1 compartment, a separated part
      of the house where the hens could move around freely, of a tiered-wired-floor
      aviary system (TWF-system). An automatic egg weighing and counting system (EWACS)
      was used to count and weigh eggs daily from 2 tiers of laying nests on 1 side of
      the compartment and the number of eggs for the whole compartment were counted
      daily by the farmer. Each tier was divided into 16 blocks of 5 individual laying
      nests. Two adjoining blocks were called a group. To prevent hens from walking
      along all the laying nests in a tier, partitions were placed on the perches in
      front of the laying nests, between nest groups 2-3, 4-5, and 6-7. 3. After the
      first 3 weeks of the laying period, the distribution of egg numbers over the nest
      groups within a tier became stable. If egg numbers were counted daily from only 1
      nest group the coefficient of variation was 23.1%. If the eggs from the whole
      compartment were counted daily, the coefficient of variation for the number of
      eggs was 2.8%. The nest group, presence of a partition and tier level influenced
      the daily number of eggs. 4. The distribution of the mean egg weight over the
      different nest groups within a tier was stable for the whole laying period. The
      coefficient of variation of the daily mean egg weight for a nest group was 3.1%.
      The difference in mean egg weight between nest groups was small, between 0.1 and
      0.6 g, and the level of tiers and the presence of partitions between nest groups
      had no effect on the mean egg weight. 5. It could be concluded that egg numbers
      could not be estimated reliably by taking samples from a group of laying nests or
      a tier, but that it was necessary to count all the eggs from a compartment. The
      daily mean egg weight, however, could be estimated reliably on the basis of a
      sample of eggs from a nest group or a tier. By using EWACS frequent samples could
      be taken, which diminished the coefficient of variation so that the reliability
      of the data increased.

PMID- 8746972
TI  - The Edinburgh modified cage for laying hens.
AB  - 1. Behaviour, production and welfare of ISA Brown medium hybrids were assessed in
      2 trials (each from 20 to 44 weeks of age) of a novel design of cage for laying
      hens: the Edinburgh Modified Cage (EMC). 2. The EMC was 600 mm wide, 450 mm deep
      and 450 mm high at the rear; it had a softwood perch and at one side a 250 mm
      wide nest box (containing litter or artificial turf) with a dust bath directly
      above. It housed 4 birds and provided 675 cm2/bird in the main cage with an
      additional 281 cm2/bird in the nest box. The nest box and dust bath had
      automatically controlled doors which were closed at night. There were 18 EMC; in
      the first trial these were compared with 6 control cages with perch but without
      next box or dust bath. 3. Hens spent 32 to 37% of day time on the perch, 5 to 7%
      in the dust bath and 5 to 6% in the nest. At night 92 to 98% roosted on the
      perch. 4. Initially only 55 to 70% of eggs were laid in the nest box partly
      because some eggs were laid before dawn. Once the door was retimed to open 3h
      before lights-on the proportion rose to 91 to 96%. Very few eggs were laid in the
      dust bath. Pre-laying behaviour lasted longer in treatments with nest boxes (55
      to 76min) than in control cages (48min); disturbance was slight in all
      treatments, but lowest in control cages. 5. Dust baths were well used, with on
      average 61% of hens dust bathing during a 3-h afternoon observation period
      compared with only 17% in control cages. Two birds could use the dust bath
      simultaneously. 6. It was concluded that although a number of minor design
      features still required attention the EMC has potential to reduce the
      disadvantages of conventional cages for welfare while retaining their advantages
      and has possible commercial application.

PMID- 8746973
TI  - Divergent selection for residual food intake in Rhode Island red egg-laying
      lines: gross carcase composition, carcase adiposity and lipid contents of
      tissues.
AB  - 1. A sample of 48 hens and cockerels from generation 17 of a divergent selection
      experiment on residual food intake was examined to determine whether the large
      food intake differences between those lines were associated with differences of
      body composition. 2. Adiposity and lipid contents of various parts of the carcase
      were higher in the low residual food intake line than in the high residual food
      intake line, both in males and females, with the cockerels of the high residual
      food intake line markedly lean. 3. On an equal weight basis obtained by linear
      correction for body weight differences, males had heavier thigh, drumstick and
      bones, but less adipose tissue and smaller amounts of lipids in the liver, meat,
      skin and abdominal adipose tissue than females.

PMID- 8746974
TI  - Individual and combined effects of aflatoxin and gizzerosine in broiler chickens.
AB  - 1. The individual and combined effects of aflatoxin B1 (AFB1) and DL-gizzerosine
      (GIZZ) in growing broiler chickens were investigated in a 7-d fully randomised
      trial consisting of 7 dietary treatments (1 and 4 mg GIZZ/kg, 0.66 and 3 mg
      AFB1/kg, the combinations 1 mg GIZZ/kg/0.66 mg AFB1/kg and 4 mg GIZZ/3 mg
      AFB1/kg, and a control basal diet without GIZZ or AFB1). 2. Dietary GIZZ at 1
      mg/kg caused moderate gizzard erosions without affecting performance, whereas 4
      mg/kg GIZZ induced severe erosion, ulceration and perforation of the gizzard; and
      significantly affected performance. 3. Dietary AFB1 at 0.66 or 3 mg/kg did not
      induce lesions in the gizzard or cause any adverse effects on chick performance.
      4. No apparent toxicologic interaction was observed between AFB1 and GIZZ when
      they were given simultaneously at relatively low dietary concentrations (0.66
      mg/kg AFB1 + 1 mg/kg GIZZ). However, at higher dietary concentrations (3 mg/kg
      AFB1 + 4 mg/kg GIZZ), AFB1 potentiated the lethality of GIZZ. 5. The combination
      3 mg/kg AFB1/4 mg/kg GIZZ was more toxic than the same concentrations of single
      toxins and may pose a greater economic threat to the poultry producer than either
      toxin individually.

PMID- 8746975
TI  - Effect of restricted feeding during the rearing period and a "forced moult" at 40
      weeks of production on the productivity of Pekin breeder ducks.
AB  - 1. Six males and 24 female Cherry Valley Pekin ducklings were randomly allocated
      to each of 12 pens to test the effects of quantitative food restriction during
      the rearing period on the subsequent reproductive performance. At the end of the
      laying period (60 weeks) a "forced moult" was introduced and its effect on a
      further 40 weeks production investigated. 2. The 3 rearing treatments were 50% of
      ad libitum intake from 3 to 20 weeks; 75% of ad libitum intake from 3 to 20 weeks
      and ad libitum intake throughout. During the laying period (20-60 weeks) and post
      forced-moult period (60-100 weeks) duck breeder pellets were fed ad libitum to
      all groups. 3. Highly significant (P < or = 0.01) differences in favour of the
      restricted groups over the ad libitum-fed groups were observed in most of the
      responses studied. The following were the main advantages of food restriction:
      lower lifetime food intake, lower carcase fat content at 20 weeks, delay in
      sexual maturity, higher egg production, higher peak and terminal production,
      higher fertility, higher hatchability of eggs set and lower mortality. Egg mass
      and hatchability of fertile eggs was not influenced by food restriction in this
      experiment. The use of a "forced moult" showed that it could be of economical
      importance. 4. Difference between treatments in respect of absolute and relative
      visceral masses were also investigated. The absolute masses of the intestine,
      heart, gizzard and liver all decreased as the degree of food restriction
      increased. The relative visceral masses showed the opposite trend with the
      exception of the heart which showed no significant differences between
      treatments.

PMID- 8746976
TI  - Effects of dietary sulphur-containing amino acids on performance and breast meat
      deposition of broiler chicks during the growing and finishing phases.
AB  - 1. Two growth trials were performed to measure the effects of dietary methionine
      and cystine (SAA) on growth rate, food conversion efficiency and breast meat
      deposition in male broilers. 2. In experiment 1, broilers were grown on 6
      experimental diets covering a range from 6.9 to 9.6 g SAA/kg. The diets were fed
      from 15 to 33 d of age. Similarly, in experiment 2, 6 diets containing 6.0 to 8.5
      g SAA/kg were fed to finishing broilers 33 to 43 d of age. In each experiment 60
      birds per treatment were processed, and carcase yield and breast meat percentage
      were determined. 3. Significant responses in weight gain, efficiency of food
      conversion and breast meat percentage were detected, which could be described
      well by exponential regression curves. Dietary SAA requirements to obtain maximum
      efficiency of food utilisation and maximum breast meat deposition were estimated
      to be about 9.0 g/kg from 15 to 33 d of age, and about 8.0 g/kg from 33 to 43 d
      of age. 4. Economic aspects were considered to calculate optimum SAA
      specifications from the results. In both trials, the dietary optimum of SAA was
      found to be higher for birds to be further processed than for birds to be
      marketed as whole carcases.

PMID- 8746977
TI  - A test for photorefractoriness in high-producing stocks of laying pullets.
AB  - 1. Pullets of 2 high-producing commercial stocks (both brown-egg layers) were
      exposed to 5 different lighting patterns between 18 and 72 weeks to test the
      hypothesis that photoperiods used in commercial lighting programmes early in the
      laying year may be unnecessarily long and, by accelerating the development of
      photorefractoriness, may contribute to the decline in egg production observed
      after the initial peak. Two rooms of 288 pullets were allocated to each
      treatment. 2. The rate of lay observed with a Step-Up treatment which gave
      increases in photoperiod from 8L:16D at 18 weeks to 15L:9D at 27 weeks of age was
      not significantly different from that of treatments which held the birds on
      11L:13D during peak egg production but gave increments up to 15L:9D later in the
      laying year. 3. A control group maintained on 11L:13D from 20 to 72 weeks laid
      295 eggs per bird housed and a further group held on 8L:16D from 0 to 72 weeks
      laid 284 eggs per bird. These yields were lower than the Step-Up treatment (299
      eggs) but show the potential of modern hybrid stocks to lay prolifically even
      without light stimulation. 4. It is concluded that the stocks tested in this
      experiment showed no advantage when given lighting programmes in the first laying
      year which were designed to minimise the adverse effects of photorefractoriness.

PMID- 8746978
TI  - Effect of age and carcase composition on the onset of sexual maturity in quail
      under normal feeding regimens.
AB  - 1. The effect of age and carcase composition on the onset of sexual maturity was
      investigated in Japanese quail (Coturnix coturnix japonica) reared under a normal
      feeding regimen. 2. At 42 d of age, when the quail had started to lay and hen day
      production was about 60%, layers were heavier and contained more carcase fat than
      those that were not laying. 3. The liver and the ovary weight were greater
      following the onset of sexual maturity than 1 or 2 weeks before (35 and 28 d
      respectively). 4. Carcase fat as well as age are critical requirements for the
      onset of sexual maturity in quail.

PMID- 8746979
TI  - Developmental changes in immunoreactive inhibin and FSH in plasma of chickens
      from hatch to sexual maturity.
AB  - 1. The relationship between immunoreactive inhibin and follicle-stimulating
      hormone (FSH) was studied in male and female chickens from hatch to sexual
      maturity. Plasma inhibin was estimated by a heterologous radioimmunoassay
      validated for use in the chicken. FSH was measured by a recently developed
      homologous radioimmunoassay. 2. In a cross-sectional study, blood samples and
      gonads were collected from chickens of both sexes at 1, 3, 5, 7, 14, 21 and 28 d
      after hatching and subsequently at 14-day intervals until 182 d of age. 3. In the
      female, plasma progesterone concentration (P4) progressively increased during
      sexual development. The plasma luteinising hormone (LH) concentration rose during
      the first week after hatching, and fluctuated thereafter, with troughs at 6 and
      14 weeks and peaks at weeks 10 and 18. The plasma inhibin and FSH concentrations
      remained low until the start of puberty and increased simultaneously thereafter.
      However, from week 18 on, plasma inhibin continued to rise while plasma FSH fell.
      Hence, FSH and inhibin were positively correlated before puberty, but developed a
      negative correlation during sexual maturation. 4. In the male, plasma
      testosterone and LH concentrations increased 38- and 3.7-fold respectively over
      the period studied. Inhibin and FSH followed similar time courses and were
      consequently positively correlated. 5. These results suggest sex differences in
      the role of inhibin in regulating FSH secretion during development. The FSH
      inhibin feedback loop may become operational at the onset of sexual maturity in
      the hens. In male chickens, the similar pattern of inhibin and FSH secretion
      suggests that inhibin secretion is driven by FSH.

PMID- 8746980
TI  - Identification of tissue hypoxia in the livers of ascitic and hypoxia-induced
      broilers using trypan blue.
AB  - 1. The perfusion of livers with the vital dye trypan blue was performed to test
      for evidence of tissue hypoxia in 3 groups of young broiler chickens, namely,
      ascitic, hypoxia-induced and controls. 2. Hepatocytes that stained with trypan
      blue were considered to be dead or dying before fixation and represented damaged
      cells. 3. The proportion of trypan blue-stained hepatocytes in the livers of
      ascitic birds was slightly less than half that observed in the hypoxia-induced
      birds but significantly more than the proportion of stained cells observed in
      control birds. 4. Liver damage in the ascitic birds was also assessed
      biochemically by an altered enzyme profile. 5. The study demonstrated that
      increased trypan blue uptake in the livers of ascitic birds reared at sea-level
      may be the consequence of hypoxia stress caused by reduced oxygen utilisation.

PMID- 8746981
TI  - Effect of probiotic supplementation on serum/yolk cholesterol and on egg shell
      thickness in layers.
AB  - 1. The effect of probiotic supplementation on egg production, on serum and yolk
      cholesterol and on egg shell thickness in 24 White Leghorn layers was studied
      from 28-38 weeks of age. 2. In 3 treatments the diet was supplemented with 0, 100
      and 150 mg probiotic/kg food. 3. In the 100 mg probiotic group, egg production
      improved by 5%, and shell thickness improved slightly, with fewer thin-shelled
      eggs than in the control (8.6% compared to 18.6%). 4. The initial serum
      cholesterol concentration of 170.2 mg/dl in control birds remained similar
      throughout the 10-week experimental period, whereas in the 150 mg group the
      initial value of 176.5 mg/dl decreased to 114.3 mg by week 10. 5. Yolk
      cholesterol concentration was 14.69 mg in the control group and 11.28 and 11.37
      mg/g in the 100 and 150 mg probiotic groups respectively. Overall mean total egg
      cholesterol was thus reduced by probiotic supplementation.

PMID- 8746982
TI  - Cryopreservation of poultry semen.
AB  - 1. The effect on fertility of storing the semen of fowl, turkey, gander or drake
      at -196 degrees C in a diluent with dimethylacetamide was investigated. 2. After
      artificially inseminating ducks, geese, turkeys and hens with freeze-thawed
      semen, the percentage of fertility was 69-90%, 81-90%, 80-90% and 75-85%,
      respectively.

PMID- 8746983
TI  - Effects of in vitro corticosterone on chicken T- and B-lymphocyte proliferation.
AB  - 1. The effects of corticosterone and the time of its addition to cultures, on
      concanavalin A (Con-A) and pokeweed mitogen (PWM)-induced lymphocyte
      proliferation were studied. 2. Peripheral blood lymphocytes (PBL) were isolated
      from Cornell K-strain Single Comb White Leghorn immature male chickens and
      cultured with various concentrations of Con-A or PWM. Corticosterone, in
      different concentrations, was added to the cultures either 2 h before or 2 h
      after the addition of the respective mitogen. 3. Addition of corticosterone 2 h
      before the mitogens caused a significant suppression of lymphocyte proliferation
      in response to both Con-A and PWM stimulation. Also addition of corticosterone 2
      h after the mitogens caused significant suppression of proliferation in response
      to both mitogens; however, the degree of suppression was not as great. 4. The
      results indicate that after early activation events are initiated by the
      mitogens, lymphocytes are less sensitive to the effects of corticosterone.
      Because less suppression was seen in the cultures preincubated with PWM than
      those with Con-A, it is likely that there are different sensitivities to
      corticosterone in the cell populations that respond to these mitogens.

PMID- 8746984
TI  - Role of dietary gamma-linolenic acid in liver lipid metabolism in Japanese quail.
AB  - 1. The importance of linoleic acid (18:2n-6) itself and of dietary gamma
      linolenic acid (18:3n-6) as essential fatty acids (EFA) in Japanese quail were
      investigated with regard to liver lipid metabolism. Experimental diets were made
      by adding of 0, 2 or 4 g gamma-linolenic acid/kg, or 20 g linoleic acid/kg to an
      n-6 EFA-free diet. From 3 to 6 weeks of age, birds were fed equal amounts of
      experimental diets. 2. Liver weight and lipid content in birds fed the 2 and 4 g
      gamma-linolenic acid/kg diet were significantly lower than those in birds fed the
      gamma-linolenic acid-free diet. However, no significant difference was observed
      between the gamma-linolenic acid- and linoleic acid-supplemented diets. 3. In
      birds fed the 4 g gamma-linolenic acid/kg diet, the proportion of arachidonic
      acid in the liver lipid was similar to that in quail fed the 20 g linoleic
      acid/kg diet, implying a conversion rate from linoleic acid to gamma-linolenic
      acid of approximately 20% of whole body content. 4. It is concluded that linoleic
      acid itself is not essential for Japanese quail and that at least 2 g/kg of gamma
      linolenic acid in the diet completely prevents liver enlargement accompanied by
      lipid accumulation.

PMID- 8746985
TI  - A comparative study of laparoscopic extraperitoneal and transabdominal
      preperitoneal herniorrhaphy.
AB  - Laparoscopic minimally invasive surgical procedures are gaining popularity.
      Laparoscopic hernia repair is now less controversial and more readily acceptable,
      with at present numerous technical modifications described in an attempt to
      define the best procedure. Between November 1992 and February 1995, a
      nonrandomized trial of laparoscopic inguinal herniorrhaphy was performed on 115
      patients with a total of 120 hernias. Of these 58 patients with 60 hernias
      underwent the transabdominal preperitoneal patch repair (TAPP) without plug and
      57 patients with a total of 60 hernias were offered the extraperitoneal (EXTRA)
      approach using a distension balloon. The average operative time was 55 min for
      the TAPP and 50 min for the EXTRA procedure. The overall recurrence rate was 1.7%
      with a follow up of 1-27 months. The recurrence rate was 3.4% for the TAPP and
      none for the EXTRA approach. All patients returned to their normal activity
      within 1 week of discharge. Patients undergoing the EXTRA repair consumed less
      amount of narcotic analgesic than did the group undergoing the TAPP repair. Of
      the EXTRA group 58% did not require any analgesic, compared to 22% of the TAPP
      group (p < 05). There were no intraoperative complications. A total of 8 (6.9%)
      postoperative complications occurred in 115 patients. Four complications (6.9%)
      occurred in the TAPP procedure: 2 transient urinary retentions, 1 pulmonary
      edema, and 1 Richter's type hernia. Four (6.9%) complications occurred in the
      EXTRA procedure: 1 urinary retention, 2 abdominal wall ecchymoses, and 1 thoracic
      pain. Hospital stay was shorter for the EXTRA group: 57% were discharged the same
      day and 98% were discharged within 24 h of their operations for the EXTRA group
      compared to 10 and 84%, respectively, for the TAPP (p < 0.05). Laparoscopic
      extraperitoneal hernia repair can be accomplished with shorter hospitalization
      and less analgesic requirement than the TAPP repair. The overall incidence of
      complications, the recurrence rate, and the return to normal activity were not
      different between the two types of repair.

PMID- 8746986
TI  - Importance of accurate preoperative diagnosis and role of advanced laparoscopic
      cholecystectomy in relieving chronic acalculous cholecystitis.
AB  - Between April 1, 1989, and January 1, 1994, 38 patients with chronic acalculous
      cholecystitis underwent an advanced (3-puncture) laparoscopic cholecystectomy at
      our institution. The 30 women and 8 men had a mean age of 39 years (range, 23 to
      65 years) and represented 4.5% of our overall gallbladder patient population. In
      each case, the disease produced typical biliary colic, but no gallstones were
      visualized on ultrasound examination; cholecystokinin-stimulated
      cholescintigraphy revealed a dysfunctional gallbladder, as evidenced by an
      ejection fraction of < or = 35% or nonvisualization or nonemptying of the organ.
      In all 38 cases, cholecystectomy resulted in the complete relief of symptoms.
      Although an increasing number of physicians are recommending this operation for
      acalculous gallbladder disease, it should not be performed on the basis of
      clinical history alone. Rather, objective criteria confirming the need for
      surgical intervention should be obtained by means of appropriate preoperative
      testing, including cholecystokinin-stimulated cholescintigraphy.

PMID- 8746987
TI  - Venous hemodynamic changes during laparoscopic cholecystectomy.
AB  - Virchow's triad of venous stasis, vessel wall damage, and hypercoagulability
      cites three factors that predispose to the formation of venous thrombosis. The
      pneumoperitoneum created during laparoscopic surgery results in an intraabdominal
      pressure that exceeds the pressure of venous blood return from the legs. This may
      alter venous hemodynamics enough to result in venous stasis in the legs, thus
      increasing the risk of thrombus formation. Duplex ultrasound was used to measure
      the diameter and venous flow volume of the common femoral vein during
      laparoscopic cholecystectomy. Measurements were obtained at three different
      times: after induction of anesthesia but prior to creation of pneumoperitoneum,
      during pneumoperitoneum, and after abdominal deflation but prior to reversal of
      anesthesia. After insufflation of the abdomen, the mean cross-sectional area of
      the common femoral vein increased (0.83 to 1.15 cm2; p = 0.0024) and the venous
      flow decreased (11.00 to 6.06 cm3/sec; p = 0.0008). After deflation of the
      abdomen, there was no significant change in cross-sectional area of the common
      femoral vein, but there was an increase in venous flow (6.06 to 9.94 cm3/sec; p =
      0.0005). Abdominal insufflation during laparoscopic cholecystectomy results in
      dilation of and decreased flow in the common femoral vein. After deflation of the
      abdomen, flow in the vein returns to baseline levels.

PMID- 8746988
TI  - Laparoscopically assisted vaginal hysterectomy: a review of 106 cases.
AB  - Laparoscopically assisted vaginal hysterectomy (LAVH) was compared to total
      abdominal hysterectomy (TAH). One hundred and six cases of LAVH were compared to
      106 cases of TAH performed during the same time period. The cases were matched
      for weight and uterine weight. LAVH procedures were associated with increased
      operating room (OR) time (146.0 +/- 3.4 vs 61.9 +/- 2.3 min), decreased length of
      postoperative stay (3.5 +/- 0.14 vs 6.4 +/- 0.18 days) and decreased total
      narcotic use (527 +/- 40 vs 983 +/- 74 mg meperidine) compared to the TAH group.
      There was no difference in the complication rate between the two groups.
      Procedure costs were $4073.78 for the LAVH group and $4699.61 for the TAH group.
      LAVH is an alternative to TAH and has an acceptable complication rate.

PMID- 8746989
TI  - Intraoperative trans-gallbladder cholangiography intended to delineate bile duct
      anatomy.
AB  - Intraoperative cholangiography has been recommended to lower the incidence and
      severity of biliary tract injury during laparoscopic cholecystectomy. However a
      literature review of common bile duct (CBD) injuries does not appear to support
      this concept. Most cystic duct cholangiographies disclose the injury after the
      fact. This study was designed to compare the technical difficulties and
      complications of laparoscopic cholecystectomy in three groups of patients: Group
      1 underwent intraoperative cholangiography through the gallbladder (n = 288),
      group 2 underwent intraoperative cholangiography through the cystic duct (n =
      162), and group 3 did not undergo cholangiography (n = 227). Cholecystectomies
      were defined as "difficult" if there was a need to convert to open procedure in
      the absence of an accidental complication, or if estimated blood loss was over
      100 ml, and/or if operating time was over 2 h. Difficult cholecystectomies were
      encountered in 34% of patients in group 2 and 28.2% of patients in group 3, but
      in only 7.6% of patients in group 1. Technical complications (bleeding, bile
      leak, common bile duct injury, retained common bile duct stones, false positive
      choledocholithiasis, pancreatitis, and trocar injuries) occurred in 11.7% of
      cases in group 2, 4.4% in group 3, and in only 1.4% of group 1. Intraoperative
      cholangiography performed through the gallbladder before any dissection was
      initiated significantly facilitated the operation and helped decrease the
      incidence of technical complications.

PMID- 8746990
TI  - Direct retroperitoneoscopic adrenalectomy in the porcine model.
AB  - An experimental protocol was developed to determine the safety and feasibility of
      retroperitoneoscopic adrenalectomy in the porcine model. We describe the
      technique and our experience with this exciting new endoscopic surgical modality.

PMID- 8746991
TI  - Laparoscopic upper abdominal operations and mesenteric infarction.
AB  - Mesenteric visceral infarction occurring after laparoscopic procedures in the
      upper abdomen may be a direct result of physiologic changes induced by carbon
      dioxide pneumoperitoneum and other technical elements with these procedures. The
      reported case is characteristic of a seemingly successful operative result
      interrupted by this devastating complication.

PMID- 8746993
TI  - Management of choledocholithiasis during pregnancy: a new protocol in the
      laparoscopic era.
AB  - The management of symptomatic cholelithiasis during pregnancy remains a serious
      and difficult problem. This condition may be further complicated by the presence
      of common bile duct stones (CBDS). Two cases of CBDS in pregnancy are presented.
      During the period from August 1990 to June 1994, 1127 consecutive patients
      underwent LC by a single surgical team. Two (0.2%) of these patients were
      pregnant and both were found to have choledocholithiasis. One patient's stones
      were lavaged into the duodenum via the cystic duct and the other patient had
      transcystic choledochoscopy and transcystic duct tube drainage. The patients were
      discharged from the hospital on postoperative days 4 and 6, respectively. There
      were no complications and both successfully carried their pregnancies to term.
      Laparoscopic cholecystectomy (LC) with transcystic common bile duct exploration
      (TCDE) was advantageous in both patients. Neither patient required an abdominal
      incision or choledochotomy. Laparoscopic TCDE with or without cystic tube
      drainage is a viable option in the management of CBDS in the pregnant patient.

PMID- 8746992
TI  - Laparoscopically assisted transperineal interstitial brachytherapy with omental
      flap for locally recurrent endometrial cancer.
AB  - In most cases, Syed-Neblett template placement is blind with respect to
      intraperitoneal structures. We evaluated the feasibility of laparoscopic
      assistance to add a potentially useful dimension to this technique. Two patients
      successfully underwent laparoscopic lysis of pelvic adhesions, assisted needle
      placement and creation of an omental pelvic carpet to protect the small
      intestine. The procedure resulted in avoidance of direct vascular and bowel
      injury and more appropriate depth of needle placement at 24 and 26 month follow
      up, there is no evidence of radiation induced complications. The technique of
      laparoscopically assisted Syed-Neblett placement as described is feasible and may
      decrease operative and radiation associated morbidity.

PMID- 8746994
TI  - Laparoscopic repair of a traumatic diaphragmatic hernia.
AB  - The laparoscopic diagnosis and repair of an unusual diaphragmatic hernia are
      described. Extensive radiological assessment failed to demonstrate the injury,
      which was diagnosed by laparoscopy 5 weeks after the initial presentation. The
      diaphragmatic tear was adjacent to the costal margin and was repaired using a
      novel percutaneous technique. The place of laparoscopy in blunt abdominal trauma
      is discussed.

PMID- 8746995
TI  - Lost gallstones found in a hernial sac.
AB  - Spillage of bile and gallstones is not a rare event during laparoscopic
      cholecystectomy. The natural history of spilled and retained stones is not well
      defined. We report of such lost stones that were found several months later in a
      hernia sac.

PMID- 8746996
TI  - Laparoscopic approach to cholecystocolic fistula: report of a case.
AB  - The development of a fistulous tract from the gallbladder is associated with
      gallstones in 90% of cases. Cholecystocolic fistula (CCF) accounts for 10 to 20%
      of all enteric biliary fistulas. The conventional treatment advocated is
      cholecystectomy and closure of the fistulous communication. In this report a case
      of a patient whose only complaint was severe diarrhea is described. CCF was
      demonstrated by barium enema. The patient was treated by laparoscopic surgery.
      The case history and laparoscopic approach to enteric biliary fistula are
      described.

PMID- 8746997
TI  - Laparoscopic appendectomy.

PMID- 8746998
TI  - Pharmacological basis for duration of effect: formoterol and salmeterol versus
      short-acting beta 2-adrenoceptor agonists.
AB  - The mechanisms behind the long duration of bronchodilating action of the beta 2
      adrenoceptor agonists formoterol and salmeterol are only partially understood.
      This review compares pharmacological characteristics of long-acting versus short
      acting beta 2-adrenoceptor agonists in human and animal airways. Based upon the
      reviewed evidence, it is concluded that for beta 2-adrenoceptor agonists, long
      duration of action may depend upon several factors. Both formoterol and
      salmeterol display a higher lipophilicity and have a higher affinity,
      selectivity, and potency than most short-acting agonists at the beta 2
      adrenoceptor. Of these factors, lipophilicity may prove to be one of the most
      important ones by determining the amount of drug entering into the cell membrane
      in the vicinity of the beta 2-adrenoceptor. However, the receptor affinity,
      maximal relaxant effect (efficacy or intrinsic activity), potency, and receptor
      selectivity may also be of importance in determining how much beta 2-adrenoceptor
      agonist must remain at the receptor for sustained action.

PMID- 8746999
TI  - Occupational asthma due to isocyanates.

PMID- 8747000
TI  - Susceptibility to amiodarone-induced pulmonary toxicity: relationship to the
      uptake of amiodarone by isolated lung cells.
AB  - In previous studies, we showed that Fischer rats fed 175 mg/kg of amiodarone
      accumulated large amounts of drug and metabolite in the lung and developed
      pulmonary toxicity, whereas Wistar rats fed the same drug dose had significantly
      less amiodarone in the lung and did not develop pulmonary inflammation. The
      present study was designed to determine whether this difference in susceptibility
      between the strains was related to differences in uptake of amiodarone by lung
      cells. We found that isolated mixed lung cells of Fischer rats sequester
      significantly more drug than cells from Wistar rats. This difference in uptake
      cannot be due to drug metabolism because the lung is not capable of metabolizing
      amiodarone. We also found that the alveolar macrophage is one of the cell types
      in the mixed cell population that is partially responsible for the difference in
      drug uptake and that fibroblasts and type II pneumocytes are not involved. In
      addition, despite the fact that there was no difference in drug uptake, we found
      that fibroblasts isolated from Fischer rats were more susceptible to amiodarone
      induced cytotoxicity than were Wistar fibroblasts. We conclude that genetic
      differences in lung drug sequestration and possibly the sensitivity to
      cytotoxicity may explain differences in susceptibility to amiodarone-induced
      pulmonary toxicity.

PMID- 8747001
TI  - Computerized single-breath nitrogen washout: predicted values in a rural French
      community.
AB  - Comparative manual and computer measurements of the alveolar N2 slope and closing
      volumes have indicated systematic differences. When a computerized system is used
      in field surveys, predicted values are to be obtained under the same conditions.
      Therefore, we measured the alveolar nitrogen slope (phase III, PIII), closing
      volume (CV), and closing capacity (CC) from single-breath N2 washout maneuvers in
      158 healthy subjects (68 females), ages 21 to 64 years, from a rural community
      living in a nonpolluted area of northeast France. PIII, the CV to vital capacity
      ratio (CV:VC, %), and the CC to the total lung capacity ratio (CC:TLC, %) were
      regressed against age, height, weight, and the body mass index (BMI, kg/m2) and
      prediction equations with 95% confidence intervals were computed. PIII increased
      with age in both sexes and tended to decrease with height in males (r = -0.19, p
      = .08). The CV:VC and CC:TLC ratios depended on age and, in males, increased with
      the BMI. Despite accepting a 15% difference between the test VC and the
      spirometric VC, only 46.3% of asymptomatic nonsmokers produced a valid single
      breath nitrogen washout (SBN2) test. This high failure rate limits the usefulness
      of the test for epidemiologic purposes when older populations "naive" to
      pulmonary function testing are studied under field-survey conditions.

PMID- 8747002
TI  - Modulation of IL-1 beta, IL-6, IL-8, TNF-alpha, and TGF-beta secretions by
      alveolar macrophages under NO2 exposure.
AB  - Activated alveolar macrophages (AMs) secrete interleukine (IL)-1 beta, IL-6, IL
      8, tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta
      (TGF-beta), whose inflammatory and fibroblast-activating characteristics may play
      a role in the maintenance of pulmonary inflammatory processes and subsequent
      fibrosis. Human AMs were transferred to a gas cylinder and exposed to NO2 in
      concentrations ranging from 0.1 to 0.5 ppm in synthetic air for 30 min at 37
      degree C. AMs were fixed on a polycarbonate membrane and placed on culture
      medium. A culture was established, with the exposed AM (nonstimulated or
      stimulated with 1 microgram/ml lipopolysaccharide [LPS]), and the remaining cells
      were used to determine the cytokines. IL-1 beta, IL-6, and IL-8 were quantified
      by commercial enzyme-linked immunosorbent assay kits (ELISA kits). TNF-alpha was
      determined with a "sandwich" ELISA, using the biotin-streptavidin system. NO2
      exposure of nonstimulated AM did not result in changes in IL-1 beta, IL-6, TNF
      alpha, and TGF-beta release, compared to the situation with control experiments.
      Exposure for 30 min to NO2 induced a significant decrease of LPS-stimulated IL-1
      Beta, IL-6, IL-8, and TNF-alpha (p < .05). The release of TGF-beta was not
      significantly affected by NO2 exposure. Cytotoxicity of AM was checked by trypan
      blue exclusion, with values ranging from 1.3 to 3.0%. NO2 exposure of LPS
      stimulated AM resulted in a functional impairment of AM after NO2 exposure
      regarding IL-1 beta, IL-6, IL-8, and TNF-alpha. Neither the spontaneous nor the
      stimulated release of TGF-beta were influenced by NO2.

PMID- 8747004
TI  - Nobody said it would be easy.

PMID- 8747003
TI  - Education: a first step in solving the planet's pollution problems.

PMID- 8747005
TI  - What's in a name?

PMID- 8747006
TI  - Intriguing innovation.

PMID- 8747007
TI  - Malaria carriers.

PMID- 8747008
TI  - Pesticides in baby food.

PMID- 8747009
TI  - Milk may do a body good.

PMID- 8747011
TI  - Consequences of climate change.

PMID- 8747010
TI  - New clues to cell death.

PMID- 8747012
TI  - What more of us means.

PMID- 8747013
TI  - Livestock legacy.

PMID- 8747014
TI  - Contraband in the stratosphere.

PMID- 8747015
TI  - Absorbing possibilities: phytoremediation.

PMID- 8747016
TI  - Use of outpatient clinics as a health indicator for communities around a coal
      fired power plant.
AB  - The permit to operate the first coal fired power plant in Israel was issued with
      the condition that a comprehensive network to monitor its effects on the
      environment, health, and agriculture must be installed and operated around the
      plant. The health monitoring system consists of four studies, which started 1
      year prior to the operation of the plant and were carried out for 10 years. In
      the framework of the health monitoring system, a study of requests for health
      services was carried out. In this survey, 8 clinics of the Sick Fund, served by
      16 physicians, were followed up. The clinics were located as near as possible to
      air pollution monitoring stations and represent expected different levels of
      pollution. A health recorder summarized each day's visits to each physician and
      tabulated the total visits for each day and the visits due to respiratory tract
      complaints. Multivariate stepwise regressions on total as well as on respiratory
      complaints were carried out. The independent variables in the regressions were
      sulfur dioxide, meteorological parameters (such as temperature and humidity), and
      flu epidemics. Temperature was almost always significantly correlated with
      respiratory complaints, but less correlated with total visits among, adults and
      children. Sulfur dioxide, most meterological parameters and flu epidemics were
      not meaningful explanatory factor in the regressions. Ambient air pollution
      levels did not exceed the Israeli air quality or the more stringent local air
      quality standards, the monthly and annual average sulfur dioxide and nitrogen
      oxides values were very low.

PMID- 8747017
TI  - Genetic control of cadmium tolerance in Drosophila melanogaster.
AB  - Files from a transgenic line of Drosophila melanogaster with two copies of the
      metallothionein allele Mtn3 were more tolerant to cadmium than strains with only
      one copy of the gene. However, flies with the Mtn3 allele were as tolerant as
      flies with the Mtn3 allele, despite the level of expression of Mtn3 being three
      times higher than of Mtn3. We propose that the substitution of Lys-40 (in Mtn3)
      for Glu-40 (in Mtn1) accounts for a reduction in binding affinity of Mtn1, which
      offsets the increased expression levels.

PMID- 8747018
TI  - Reduced birthweight and length in the offspring of females exposed to PCDFs, PCP,
      and lindane.
AB  - The objective of this study was to investigate a broad range of adverse health
      outcomes and their potential association to wood preservative used in daycare
      centers. This article focuses on reproductive effects. A sample of 221 exposed
      teachers was provided by the employer's liability insurers. A comparison group (n
      = 189) insured by the same two organizations was recruited from nonexposed
      daycare centers. In a face-to-face interview, job history and reproductive
      history of 398 female teachers were ascertained. Data on exposure were provided,
      including measurements on concentration of pentachlorophenol (PCP) and lindane in
      wood panels, and of PCP, lindane, polychlorinated dibenzo-p-dioxins and
      dibenzofurans in indoor air. An exposure matrix based on individual job history,
      independent exposure information from each center, and reproductive history was
      set up with regard to the vulnerable time windows for each pregnancy. Using this
      approach, 49 exposed and 507 nonexposed pregnancies were identified, including 32
      exposed and 386 nonexposed live births. For subgroup analyses the observations
      were restricted to independent pregnancies, excluding multiple and consecutive
      births. The data were analyzed with linear regression techniques, taking
      confounders into account. The crude median difference between exposed and
      nonexposed was 175 g in birthweight and 2 cm in length. Controlling for
      confounders, the results show a significantly reduced but weight (p = 0.04) and
      length (p = 0.02) in exposed pregnancies, even after restricting the data to
      independent pregnancies and pregnancies for which data could be validated from
      the mother's health cards. These differences were not explained by differences in
      gestational age indicating that a toxic effect, which could cause small-for date
      newborns, might have affected the fetus.

PMID- 8747019
TI  - Pesticides in household dust and soil: exposure pathways for children of
      agricultural families.
AB  - Child of agriculture families are likely to be exposed to agricultural chemicals,
      even if they are not involved in farm activities. This study was designed to
      determine whether such children are exposed to higher levels of pesticides than
      children whose parents are not involved in agriculture and whose homes are not
      close to farms. Household dust and soil samples were collected in children's play
      areas from 59 residences in eastern Washington State (26 farming, 22 farmworker,
      and 11 nonfarming families). The majority of the farm families lived within 200
      feet of an operating apple or pear orchard, whereas all reference homes were
      located at least a quarter of a mile from an orchard. Four organophosphorous (OP)
      insecticides commonly used on tree fruit were targeted for analysis:
      azinphosmethyl, chlorpyrifos, parathion, and phosmet. Samples were extracted and
      analyzed by gas chromatography/mass selective detection. Pesticide concentrations
      in household dust were significantly higher than in soil for all groups. OP
      levels for farmer/farm-worker families ranged from nondetectable to 930 ng/g in
      soil (0.93 ppm) and from nondetectable to 17,000 ng/g in dust (17 ppm); all four
      OP compounds were found in 62% of household dust samples, and two-thirds of the
      farm homes contained at least one OP above 1000 ng/g. Residues were found less
      frequently in reference homes and all levels were below 1000 ng/g. Household dust
      concentrations for all four target compounds were significantly lower in
      reference homes when compared to farmer/farmworker homes (Mann Whitney, U test; p
      < 0.05). These results demonstrate that children of agricultural families have a
      higher potential for exposure to OP pesticides than children of nonfarm families
      in this region. Measurable residues of a toxicity, I compound registered
      exclusively for agricultural use, azcnphosmettyl were found in household dust
      samples from all study homes, suggesting that low level exposure to such
      chemicals occurs throughout the region. Children's total and cumulative exposure
      to this pesticide class from household dust, soil, and other sources warrants
      further investigation.

PMID- 8747020
TI  - Gestational and lactational exposure of rats to xenoestrogens results in reduced
      testicular size and sperm production.
AB  - This study assessed whether exposure of male rats to two estrogenic,
      environmental chemicals, 4-octylphenol (OP) and butyl benzyl phthalate (BBP)
      during gestation or during the first 21 days of postnatal life, affected
      testicular size or spermatogenesis in adulthood (90-95 days of age). Chemicals
      were administered via the drinking water or concentrations of 10-1000
      micrograms/l (OP) or 1000 micrograms/l (BBP), diethylstilbestrol (DES; 100
      micrograms/l) and an octylphenol polyethoxylate (OPP; 1000 micrograms/l), which
      is a weak estrogen or nonestrogenic in vitro, were administered as presumptive
      positive and negative controls, respectively. Controls received the vehicle
      (ethanol) in tap water. In study 1, rats were treated from days 1-22 after births
      in studies 2 and 3, the mothers were treated for approximately 8-9 weeks,
      spanning a 2-week period before mating throughout gestation and 22 days after
      giving birth. With the exception of DES, treatment generally had no major adverse
      effect or body weight: in most instances, treated animals were heavier than
      controls at day 22 and at days 90-95. Exposure to OP, OPP, or BBP at a
      concentration of 1000 micrograms/1 resulted in a small (5-13%) but significant (p
      < 0.01 or p < 0.0001) reduction in mean testicular size in studies 2 and 3, an
      effect that was still evident when testicular weight was expressed relative to
      body, weight or kidney weight. The effect of OPP is attributed to its metabolism
      in vivo to OP. DES exposure caused similar reductions in testicular size but also
      caused reductions in body weight, kidney weight, and litter size. Ventral
      prostate weight was reduced significantly in DES-treated rats and to minor extent
      in OP-treated rats. Comparable but more minor effects of treatment with DES or OP
      on testicular size were observed in study 1. None of the treatments had any
      adverse effect on testicular morphology or on the cross-sectional area of the
      lumen or seminiferous epithelium at stages VII-VIII of the spermatogenic cycle,
      but DES, OP, and BBP caused reductions of 10-21% (p < 0.05 to p < 0.001) in daily
      sperm production. Humans are exposed to phthalates, such as BBP, and to
      alkylphenol polyethoxylates, such as OP, but to what extent is unknown. More
      detailed studies are warranted to assess the possible risk to the development of
      the human testis from exposure to these and other environmental estrogens.

PMID- 8747021
TI  - Effects of residential mobility on individual versus population risk of radon
      related lung cancer.
AB  - The U.S. Environment Protection Agency (EPA) does not consider the effects of
      normal patterns of residential mobility in estimating individual radon-related
      lung cancer risks. As a consequence, the EPA's population risk estimates may have
      little bearing on individual risks, and remediation of high-radon homes may have
      only small health benefits for the individual who remediate their homes. Through
      a stimulation analysis, we examine the effects of residential mobility on random
      exposure and lung cancer risk. Given normal mobility, only 7% of eventual radon
      related mortality among current 30 year old will occur in the 5% currently living
      in homes above pCi/l (the EPA's action level for remediation) in contrast with
      you estimate of 31% of deaths when mobility's ignored. About 10 pCi/l the no
      mobility assumption implies 10.3% of deaths, compared to only 0.4% when mobility
      taken into account. We conclude that knowledge of one's current random exposure
      not necessarily a useful guide to one's risk, especially for residents of the
      high-radon homes targeted for remediation by the EPA. The risk of such
      individuals is like to be substantially lower than that implied in the EPA's risk
      charts. If people currently living in high radon homes remediate their houses,
      the majority of the resulting health benefits will accrue to future occupants of
      their homes.

PMID- 8747022
TI  - Hormone replacement therapy may reduce the return of endogenous lead from bone to
      the circulation.
AB  - Hormone replacement therapy (HRT) in postmenopausal women suppresses the increase
      in bone resorption expected as circulating levels of endogenous estrogen decline.
      We tested the hypothesis that bone lead content might remain elevated in women on
      HRT. Fifty six women who at recruitment were on average 35 years postmenopausal
      were placed on calcium supplementation. Six months later 33 of these women were
      prescribed either low dose or moderate dose hormone replacement in addition to
      the calcium supplementation. After approximately 4 years of hormone replacement,
      lead content was measured at the tibia and calcaneus by in vivo fluorescence
      excitation, and lead concentrations were measured in serum, whole blood, and
      urine. Women not taking hormones had significantly lower lead concentrations in
      cortical bone compared to all women on HRT (p = 0.007). Tibia lead content (mean
      +/- SD) for women on calcium only was 11.13 +/- 6.22 microgram/g bone mineral.
      For women on HRT, tibia bone lead was 19.37 +/- 8.62 micrograms/g bone mineral on
      low-dose HRT and 16.87 +/- 11.68 micrograms/g bone mineral on moderate-dose HRT.
      There were no differences between groups for lead concentrations measured in
      trabecular bone, whole blood, serum or urine. Hormone replacement maintains
      cortical bone lead content. In women not on HRT, there will be a perimenopausal
      release of lead from bone.

PMID- 8747023
TI  - Importance of breaking a spermatozoon's tail before intracytoplasmic injection: a
      prospective randomized trial.

PMID- 8747024
TI  - Experience with oocyte donation and intracytoplasmic sperm injection.

PMID- 8747025
TI  - Treatment of severe male immunological infertility by intracytoplasmic sperm
      injection.
AB  - A total of 29 infertile couples (group A) with male antisperm antibodies detected
      by the mixed antiglobulin reaction (MAR) and partly by flow cytometry (n = 21)
      were treated using an intracytoplasmic sperm injection (ICSI) technique to assist
      fertilization. In all, 22 of them had shown a poor fertilization rate (6%) in
      previous in-vitro fertilization (IVF) treatments. The fertilization and cleavage
      rates in ICSI, 79 and 89% respectively, were similar to those in a MAR-negative
      group (group B; n = 20) injected because of male infertility (68 and 93%
      respectively). A third group (group C; n = 37) with male immune infertility was
      treated by conventional IVF. All these couples had at least one oocyte
      fertilized, but the overall fertilization rate (44%) in group C was significantly
      poorer (P < 0.001) than that in the two ICSI groups. However, the embryo quality
      was lower in group A compared with that in the other groups. A total of 13
      pregnancies resulted in group A (46%), of which five ended in miscarriage. None
      of the six pregnancies (30%) in group B aborted during the first trimester. These
      results reveal, for the first time, that ICSI offers a good chance of
      fertilization for couples with male immunological infertility. However, post
      fertilization events may compromise these results because of factors not yet
      clearly understood.

PMID- 8747026
TI  - The role of intracytoplasmic sperm injection (ICSI) in the treatment of patients
      with borderline semen.

PMID- 8747027
TI  - Intracytoplasmic sperm injection in the mouse.
AB  - Intracytoplasmic sperm injection (ICSI) into mouse oocytes involves a very low
      survival rate. This study was designed to determine why ICSI frequently fails in
      mice. Metaphase II oocytes were obtained from superovulated 4-6 week old F1
      hybrid mice. Spermatozoa were retrieved from the epididymis of 12-14 week old F1
      hybrid mice. The spiked microinjection pipette used to inject a spermatozoon into
      the ooplasm had outer and inner diameters of 10 and 8 microns respectively. The
      oocytes used in the first part of the study were not activated (group 1). Some
      oocytes were incubated with calcium ionophore for 5 min (group 2). The injected
      oocytes were evaluated 6, 20, 48 and 72 h after injection. A total of 143 eggs in
      each group underwent ICSI. In group 1, sperm heads escaped into the perivitelline
      space. In all, 63 (47%) of the remaining oocytes were damaged during the
      injection or had degenerated by the first evaluation. The survival rate was 53%,
      but fertilization did not occur. In group 2, 31 oocytes (22%) were damaged during
      microinjection or soon degenerated. Two oocytes underwent accidental subzonal
      insemination. Six oocytes were fertilized (4.2%) among the 78% of survivors.
      After injection, the sperm tail was found in the cytoplasm (27 and 31% in groups
      1 and 2 respectively), the perivitelline space (45% in both groups) or protruding
      through the zona pellucida (28 and 23% respectively). More oocytes degenerated
      when the tail remained in the cytoplasm, i.e. 78% in group 1 and 36% in group 2.

PMID- 8747028
TI  - Intracytoplasmic sperm injection versus conventional in-vitro fertilization:
      first results.

PMID- 8747029
TI  - Human chorionic gonadotrophin and steroid concentrations in follicular fluid: the
      relationship to oocyte maturity and fertilization rates in stimulated and natural
      in-vitro fertilization cycles.
AB  - The study investigates the relationship of follicular fluid steroids and human
      chorionic gonadotrophin to oocyte maturity and fertilization rates in stimulated
      and natural cycles. Oestradiol, progesterone, testosterone and human chorionic
      gonadotrophin were quantified in 129 samples of follicular fluid and the
      progesterone:oestradiol ratio calculated. Both stimulated cycles (short and long
      luteinizing hormone-releasing hormone/human menopausal gonadotrophin regimens)
      and natural cycles were compared. A total of 60 women were studied, 20 in each
      group. In the natural cycles, testosterone was significantly lower in follicles
      with intermediate oocytes (P = 0.015). Both oestradiol and testosterone were
      significantly lower in stimulated cycles compared to natural cycles (P = 0.032
      and P = 0.034 respectively). In the ovarian stimulation cycles, the
      progesterone:oestradiol ratio was significantly higher when oocytes fertilized (P
      = 0.052). Moreover, in the stimulated cycles, oestradiol and human chorionic
      gonadotrophin were singnificantly lower in the short protocol compared to the
      long protocol. The data demonstrate that the hormonal milieu of the follicle is
      altered in down-regulated stimulated cycles to varying degrees, depending
      partially on the type of protocol used. Furthermore, the progesterone:oestradiol
      ratio, rather than individual hormone concentrations, may be a useful predictor
      of the fertilizing capacity of the oocytes.

PMID- 8747030
TI  - Augmentation by thyroxine of human granulosa cell gonadotrophin-induced
      steroidogenesis.
AB  - The objective of this study was to investigate the influence of thyroid hormone
      on gonadotrophin-induced oestradiol and progesterone secretion by human granulosa
      cells maintained in vitro. Granulosa cells were obtained by aspiration of pre
      ovulatory follicles from women undergoing assisted reproductive technology.
      Ovulation induction was performed with gonadotrophin-releasing hormone agonist,
      human menopausal gonadotrophin and human chorionic gonadotrophin. Granulosa cells
      were maintained in vitro in a defined medium with added insulin. Between 48 and
      72 h after the initiation of cell culture, oestradiol and progesterone secretion
      into the medium was determined for granulosa cells growing in serum-free medium
      with follicle-stimulating hormone (FSH)/luteinizing hormone (LH) and in serum
      free medium with FSH/LH and thyroxine added in a concentration range of 10(-10)
      10(-7) M. All concentrations of thyroxine used produced a statistically
      significant increase in oestradiol (range 1.18-1.37 times the amount with FSH/LH
      alone) and progesterone (range 1.29-1.51 times the amount with FSH/LH alone)
      secretion.

PMID- 8747031
TI  - Diminished luteinizing hormone biopotency in breastfeeding women.
AB  - The effect of nursing on plasma luteinizing hormone bioactivity (B-LH) and
      immunoactivity (I-LH) was assessed at 4 and 6 months post partum in fully nursing
      women who experienced their first bleeding between months 5 and 6 post partum (n
      = 6, short amenorrhoea) or after the month 6 (n = 10, long amenorrhoea). Controls
      were 10 non-nursing fertile women. Blood samples were drawn twice weekly at month
      4 post partum and at month 6 post partum. In the nursing women who were cycling
      at month 6 and in non-nursing women samples were drawn during the follicular
      phase. I-LH was measured by a time resolved immunofluorometric assay (DELFIA) and
      B-LH by the mouse Leydig cell assay. Nursing decreased B-LH more than I-LH
      resulting in a relationship between B-LH and I-LH different to that of non
      nursing women (B-LH = 2.84 x I-LH-0.16 and B-LH = 4.27 x I-LH + 3.11
      respectively, P < 0.05, by likelihood test). Plasma B-LH or I-LH were similar in
      nursing women with short or long amenorrhoea. In conclusion, nursing alters the
      quality of circulating LH, however, the decreased LH steroidogenic potency does
      not play a role in determining the duration of lactational amenorrhoea.

PMID- 8747032
TI  - Gonadotrophin surge-inhibiting/attenuating factor governs luteinizing hormone
      secretion during the ovarian cycle: physiology and pathology.
AB  - The stabilization of low luteinizing hormone (LH) concentrations during the
      period of the ovarian cycle preceding the mid-cycle LH surge seems to be of
      importance for embryo viability and survival. Several studies have stressed the
      importance of the timely excess of threshold levels of LH for optimal oocyte
      quality: LH already initiates the resumption of meiosis when a relatively low
      threshold level is reached, whereas a further outburst of LH release is necessary
      to reach the threshold level to induce ovulation. Hence, the mechanism of LH
      release should have the ability, on the one hand, to limit the LH secretion rate,
      and on the other, to allow an increased secretion rate, as during the LH surge.
      The functional antagonistic coupling of gonadotrophin-releasing hormone (GnRH)
      and the ovarian protein gonadotrophin surge-inhibiting factor or -attenuating
      factor (GnSIF/AF) provides such a mode of action for the control of LH
      concentration during the ovarian cycle. One of the important regulatory steps in
      this process is the de-novo synthesis of the so far unidentified pituitary
      proteins induced by GnRH. The induction of these proteins is a prerequisite for
      the increase in the rate of LH release. Because their synthesis is a time
      consuming process, the effect becomes visible in the typical biphasic pituitary
      LH responses to the pulsatile or continuous administration of GnRH: initially
      low, with an increase after some time. This phenomenon is also known as the GnRH
      self-priming action. It is assumed that the synthesis of these self-priming
      associated proteins is necessary to eliminate the inhibitory effect of GnSIF/AF.
      GnSIF/AF eliminates the effect of self-priming by neutralizing the biological
      activity of the pituitary proteins, which are responsible for the increased rate
      of LH release. Thus, the pituitary gland is kept in a GnRH-hyporesponsive state.
      The major advantage of such a slow protein synthesis-dependent regulatory
      mechanism is that it prevents sudden increases in the LH secretion rate in
      response to GnRH. Thus it stabilizes low LH concentrations to prevent the
      premature reinitiation of meiosis. However, the enhanced secretion of GnRH and/or
      the suppressed release or action of GnSIF/AF may finally lead to the restoration
      of the intrinsic LH responsiveness of the gonadotrophs at the start of the mid
      cycle LH surge. The antagonistic interaction between GnRH and GnSIF/AF, and its
      implication in the control of LH release under physiological and pathological
      conditions, are discussed.

PMID- 8747033
TI  - Serum progesterone at the time of human chorionic gonadotrophin does not predict
      pregnancy in in-vitro fertilization and embryo transfer.
AB  - Controversy exists as to whether the serum concentration of progesterone on the
      day of human chorionic gonadotrophin (HCG) administration following ovarian
      stimulation for in-vitro fertilization (IVF) and embryo transfer can be used to
      predict the likelihood of success. This retrospective study was undertaken to
      answer this question by analysing a large population of IVF and embryo transfer
      cycles (n = 756). In addition to the concentration of progesterone on the day of
      HCG administration, all variables known to impact on IVF and embryo transfer
      success (such as patient age), indication for IVF and embryo transfer, number of
      oocytes retrieved and the number of embryos generated and transferred were
      examined. There was a significant increase in the number of oocytes retrieved
      with increasing progesterone concentration at the time of HCG administration.
      However, there was no correlation of progesterone concentration at HCG
      administration with pregnancy and implantation rates. It is concluded that
      previous reports associating a slight elevation of progesterone in gonadotrophin
      releasing hormone agonist ovarian stimulation cycles for IVF and embryo transfer
      may be misleading because of a small sample size or the presence of confounding
      variables that affect IVF and embryo transfer success.

PMID- 8747034
TI  - Naltrexone administration modulates the neuroendocrine control of luteinizing
      hormone secretion in hypothalamic amenorrhoea.
AB  - Because endogenous opioids have been considered to be deeply involved as a causal
      factor of hypothalamic amenorrhoea, this study was designed to evaluate the
      efficacy of the administration of naltrexone, an antagonist of opioid receptors,
      on luteinizing hormone (LH) secretion in patients with hypothalamic amenorrhoea.
      A total of 30 patients with hypothalamic amenorrhoea were studied. Patients were
      divided into two groups: group A, hypogonadotrophic (n = 15), and group B,
      normogonadotrophic (n = 15). All patients were administered naltrexone at a dose
      of 50 mg/ day per os for 6 months. A third group of 10 amenorrhoeic patients was
      treated with placebo per os with the same schedule. All patients were evaluated
      for LH spontaneous pulsatile release in baseline conditions and after 3 and 6
      months of treatment. Plasma gonadal steroid concentrations increased
      significantly in all patients after 3 months of naltrexone therapy, but only
      hypogonadotrophic patients showed a sharp increase in both LH plasma
      concentrations and LH pulse amplitude within the first 3 months of treatment
      which remained unchanged until the sixth month of treatment. Plasma follicle
      stimulating hormone concentrations did not change significantly in any patient.
      Menstrual bleeding occurred within 90 days of the beginning of treatment in 24
      out of the 30 patients. Patients treated with placebo did not show a significant
      change in gonadotrophin and gonadal steroid plasma concentrations. The results of
      our study support the efficacy of naltrexone administration on neuroendocrine
      pathways controlling LH secretion in patients with hypothalamic amenorrhoea.

PMID- 8747035
TI  - Atrial natriuretic peptide, oestradiol and progesterone in women undergoing
      spontaneous and gonadotrophin-stimulated ovulatory cycles.
AB  - The objective of this study was to examine the relationship between the
      concentrations of oestradiol and progesterone on the one hand and atrial
      natriuretic peptide (ANP) concentrations on the other, during the follicular and
      luteal phases of spontaneous and gonadotrophin-stimulated ovulatory menstrual
      cycles. A total of 27 ovulatory women undergoing either a spontaneous (n = 9) or
      a gonadotrophin-stimulated (n = 18) cycle were selected for inclusion in this
      study. In comparison with spontaneous cycles, gonadotrophin-stimulated cycles had
      increased peak follicular oestradiol (mean +/- SE; 937 +/- 150 versus 195 +/- 18
      pg/ml; P < 0.05) and midluteal progesterone (mean +/- SE; 44.0 +/- 7.4 versus
      14.1 +/- 2.4 ng/ml; P < 0.05) concentrations. There were no differences in the
      circulating ANP concentrations between the follicular and luteal phases of the
      menstrual cycle. Despite the increased oestradiol and progesterone concentrations
      following gonadotrophin stimulation, no difference in ANP concentrations was seen
      between stimulated and spontaneous cycles. There was no correlation between
      circulating concentrations of oestradiol, progesterone (at physiological and
      supraphysiological concentrations) and ANP throughout the menstrual cycle.

PMID- 8747036
TI  - Effect of ovulation induction on uterine blood flow and oestradiol and
      progesterone concentrations in early pregnancy.
AB  - To determine if oestradiol and progesterone concentrations are related to uterine
      blood flow in early pregnancy, we measured these hormones at the time of vaginal
      Doppler ultrasound before and after the beginning of intervillous circulation in
      spontaneous pregnancy (group I), after clomiphene citrate administration (group
      II), and after clomiphene citrate plus human menopausal gonadotrophin (HMG)
      administration (group III). Despite large increases of oestradiol concentration
      in group II (60%) and III (300%) and of progesterone in groups II (100%) and III
      (300%), compared with group I, increases in blood flow were modest during the
      first 9 weeks of gestation. Uterine artery flow volume increased by 20% in group
      II and 33% in group III (P < or = 0.02); average velocity increased by 37% in
      group III (P < or = 0.003) compared with groups I and II; vessel diameter
      increased by 15% in groups II (P < 0.025) and III (P < 0.001) compared with group
      I; and the uterine artery resistance index decreased by 3 to 5% in group III (P =
      0.004) compared with groups I and II. Serum oestradiol and progesterone
      concentrations were unrelated to the uterine artery resistance index or volume by
      an analysis of covariance. We conclude that uterine artery blood flow is
      significantly increased during early pregnancy following HMG administration, and
      that the increase is unrelated to increases in oestradiol and progesterone
      concentrations.

PMID- 8747037
TI  - Genetic risk in micromanipulative assisted reproduction.
AB  - The empirical data on pregnancy outcome after intracytoplasmic sperm injection
      (ICSI) are encouraging, but still insufficient to rule out definitely adverse
      genetic or teratological effects. We analyse potential adverse effects of ICSI by
      applying general principles of genetic and teratological risk assessment. The
      role of gamete micromanipulation as a possible teratogen is discussed. We
      consider whether ICSI patients are at increased risk for carrying and propagating
      genetic lesions of different kinds. The possible interference of ICSI with
      genomic imprinting and pre-zygotic sperm selection is reviewed and we discuss the
      potentially protective role of DNA repair in oocytes. Considering the available
      empirical data and the conclusions from our theoretical analysis it appears that
      neither lassitude nor over-concern about adverse effects of ICSI are justified.

PMID- 8747038
TI  - An analysis of the outcome of microsurgical and laparoscopic adhesiolysis for
      infertility.
AB  - We evaluated 81 women with adnexal adhesions and no male factor who underwent
      microsurgical (n = 59) and laparoscopic (n = 22) adhesiolysis for infertility.
      The cumulative conception rates for all 81 patients at 12 and 24 months were 41
      and 44% respectively. The impact of the following variables on cumulative
      conception rates for all patients was examined: age, duration of infertility,
      type of infertility, ovulatory status, presence and stage of endometriosis,
      adhesion grade, adnexal status (bilateral or unilateral disease, unilateral tubal
      absence), history of previous surgery, history of pelvic inflammatory disease and
      treatment modality (microsurgical versus laparoscopic). The results of
      independent comparisons of subgroups within each of these variables may be biased
      because of the interrelationships between the variables. To overcome this
      problem, a stepwise Cox's proportional hazards regression analysis was employed.
      Our analysis showed that the single most significant variable influencing the
      cumulative conception rates was the duration of infertility (P < 0.005). For
      every additional year of infertility, the probability of pregnancy after
      adhesiolysis (microsurgical or laparoscopic) was reduced by approximately 20%.
      Cumulative conception rates at 12 and 24 months after microsurgical adhesiolysis
      were 36 and 40% respectively, while after laparoscopic adhesiolysis they were 57%
      at 12 and 24 months. When imbalances were adjusted between the two treatment
      groups, there was no statistically significant difference between the cumulative
      conception rates for microsurgical and laparoscopic adhesiolysis.

PMID- 8747039
TI  - An analysis of the outcome of microsurgical and laparoscopic adhesiolysis for
      chronic pelvic pain.
AB  - We evaluated the outcome of microsurgical (n = 72) and laparoscopic (n = 51)
      adhesiolysis in women who complained of chronic pelvic pain. Adhesion severity
      was not significantly different between the two treatment groups. The influences
      of the following variables on the outcome of all 123 cases of adhesiolysis were
      examined: (i) surgical modality (microsurgical or laparoscopic), (ii) history of
      infertility, (iii) associated dyspareunia and (iv) aetiological factors of
      adhesive disease (endometriosis, pelvic inflammatory disease and previous
      laparotomy). To adjust for differences in follow-up intervals, overall and
      subgroup cumulative rates of pain persistence/recurrence were calculated and
      compared. To adjust for interrelationships between variables and to correct fo
      differences between the treatment groups, a proportional hazards regression
      analysis was employed. This analysis showed that the cumulative rate of pain
      persistance/recurrence at 24 months was not significantly different after
      microsurgical (44%) and laparoscopic (53%) adhesiolysis. From all the variables
      which were examined, the only one which appeared to influence the impact of
      surgical adhesiolysis for chronic pelvic pain was a history of previous
      laparotomy. A history of previous laparotomy was associated with approximately
      three times higher rates of pain persistence or recurrence. This effect did not
      depend on whether previous laparotomy was carried out for pain or for other
      indications. The most likely explanation for the failure of these patients who
      had a previous laparotomy to respond to surgery is that they intrinsically have a
      higher rate of adhesion formation and reformation. This can only be confirmed
      with a prospective study where all patients will undergo a second-look
      laparoscopy.

PMID- 8747040
TI  - Laparoscopic findings after transvaginal ultrasound-guided aspiration of ovarian
      endometriomas.
AB  - From 1 July 1990 to 31 January 1994, 55 patients underwent operative laparoscopy
      for the excision of monolateral endometriomas. None of the patients had
      previously undergone surgery by laparotomy or laparoscopy. At the time of
      laparoscopy, the surgeon staged the disease according to the American Fertility
      Society classification of endometriosis. A second surgeon, blinded to the
      preoperative management of the patients, re-staged the disease based on a
      videotape review. Interobserver disagreement was between 0 and 12%. Total,
      endometriosis (deep and superficial) and adhesion scores were evaluated
      separately. These scores in patients who had previously undergone transvaginal
      ultrasound-guided aspiration of the cyst content (n = 13) were compared with
      those from patients who had not undergone this procedure (n = 42). The total and
      endometriosis scores were not significantly different between the two groups,
      whereas the adhesion score in patients who had undergone a transvaginal
      aspiration procedure was significantly higher than in patients who had not (mean
      +/- SD, 12.0 +/- 13.7 versus 5.9 +/- 4.6; P = 0.02). Therefore it is possible
      that transvaginal ultrasound-guided endometrioma aspiration may determine tissue
      trauma that enhances adhesion formation.

PMID- 8747041
TI  - Progestogen pretreatment in the short-term protocol does not affect the
      prognostic value of the oestradiol flare-up in response to a GnRH agonist.
AB  - The prognostic value of the oestradiol flare-up in response to gonadotrophin
      releasing hormone (GnRH) agonist was evaluated in 140 in-vitro fertilization
      (IVF) cycles programmed by progestogen pretreatment. Three days after the end of
      administration of norethisterone, a routinely used short-term DTRP6 GnRH agonist
      protocol was started (designated day 1), gonadotrophins being introduced from day
      4. Serum oestradiol flare-up values were evaluated on days 1, 2 and 3 to study
      their relationship with the subsequent IVF outcome. On day 2, 87.9% of the cycles
      exhibited a significant rise in serum oestradiol concentration from baseline
      (delta E2 > or = 5 pg/ml). Compared to cycles without any significant oestradiol
      increase, they had a higher pregnancy rate per transfer (33.3 versus 9.1%, P =
      0.02), although the number of transferred embryos did not differ significantly.
      Taking into account the previously described cut-off value (doubling from
      baseline), we found that less than half of the cycles (45.7%) involved a doubling
      of oestradiol values during flare-up, and we did not observe any significant
      difference in IVF outcome in these cycles compared to those without doubling. In
      conclusion, progestogen pretreatment, by inducing ovarian quiescence, may lower
      the oestradiol cut-off value that is predictive of the subsequent pregnancy rate.
      Nevertheless, determination of the absolute oestradiol response (delta E2) to
      GnRH agonist after progestogen pretreatment could allow a further adaptation of
      the protocol to achieve an optimum response in each cycle. Another alternative
      for patients with a lower delta E2 could be the suppression of progestogen
      pretreatment.

PMID- 8747042
TI  - Subcutaneous low dose leuprolide acetate depot versus leuprolide acetate for
      women undergoing ovarian stimulation for in-vitro fertilization.
AB  - A total of 100 women undergoing ovarian stimulation with gonadotrophin-releasing
      hormone agonist (GnRHa) and a human menopausal gonadotrophin (HMG) for in-vitro
      fertilization (IVF) participated in this randomized comparative study. Leuprolide
      acetate at a dose of 0.5 mg/day s.c. (n = 52, group I), or low-dose leuprolide
      acetate depot at a dose of 1.88 mg s.c. (n = 48, group II), was started on days
      21-23 of the cycle. Stimulation with 225 IU/day HMG was started after pituitary
      desensitization had been achieved. The luteal phase was supported by human
      chorionic gonadotrophin (HCG) i.m. injection. There were no statistical
      differences in baseline oestradiol (24.5 +/- 4.8 versus 21.9 +/- 4.5 pg/ml) and
      follicle stimulating hormone (FSH) concentrations (3.9 +/- 1.9 versus 3.2 +/- 1.8
      mIU/ml), and concentrations on the day of HCG administration of oestradiol (1657
      +/- 245 versus 1512 +/- 165 pg/ml), luteinizing hormone (LH; 6.2 +/- 4.8 versus
      5.6 +/- 4.3 mIU/ml) and FSH (10.6 +/- 2.8 versus 10.8 +/- 3.6 mIU/ml). There were
      also no statistical differences in the HMG dosage (26.8 +/- 1.8 versus 28.5 +/-
      1.5), the number of oocytes retrieved (7.6 +/- 3.0 versus 8.1 +/- 4.3), the
      number of oocytes fertilized (5.3 +/- 2.1 versus 5.6 +/- 3.0) and the number of
      embryos transferred (3.5 +/- 1.3 versus 3.4 +/- 1.6). There was no evidence of a
      premature LH surge in either group, but two patients appeared to have a poor
      response in the leuprolide acetate group (group I). There were 11 pregnancies
      (21.2%) after the use of leuprolide acetate and 12 pregnancies (25.0%) in those
      given leuprolide acetate depot; no statistical difference existed between these
      two groups. Thus, a s.c. low-dose leuprolide acetate depot injection may offer a
      useful alternative for pituitary suppression in ovarian stimulation for IVF.

PMID- 8747043
TI  - Clinical value and cumulative pregnancy rates following rigid salpingoscopy
      during laparoscopy for infertility.
AB  - This study was designed to evaluate the routine use of rigid salpingoscopy during
      diagnostic laparoscopy for infertility, and to relate the morphologic image of
      the endosalpinx with pregnancy outcome. A total of 158 consecutive patients (232
      Fallopian tubes) undergoing a diagnostic laparoscopy for infertility were
      studied. Salpingoscopy was performed at the time of diagnostic laparoscopy for
      infertility. The intraluminal image was classified using a simplified
      classification (class I-V). The relationship between this classification and the
      cumulative pregnancy rates was calculated using life table analysis. Patients
      with a normal salpingoscopy (class I and II) had a 71% cumulative pregnancy rate.
      In the intermediate group (class III) the cumulative pregnancy rate was 34%. No
      intrauterine pregnancies were observed in the group with severe intratubal
      pathology (class IV and V). Of the 107 slapingoscopies of patients with
      endometriosis 105 (98%) were class I or II. However, among patients with pelvic
      adhesions, only 42% were normal. Nine out of 50 abnormal salpingoscopies were
      found when no tubal factor was suspected during laparoscopy, without any pelvic
      adhesions. These results suggest that salpingoscopy is an important tool for
      detecting mucosal abnormalities, and for eventually referring patients for
      assisted reproductive technology. Salpingoscopy is usually normal in patients
      with endometriosis, but in patients with non-endometriotic pelvic adhesions it is
      not.

PMID- 8747044
TI  - Performance of copper intrauterine devices when inserted after an expulsion.
AB  - A total of 124 women who re-inserted a TCu-200B intrauterine device (IUD)
      following an expulsion were followed up for 1 year after the IUD re-insertion.
      The cumulative expulsion rate at 6 months was 21.7 and 31.4 per 100 women at the
      end of the first year. Women who expelled the first IUD within the first 3 months
      of use had a significantly higher expulsion rate with the second IUD. Our
      conclusion is that women who expelled a copper IUD are at a significantly higher
      risk of expelling the re-inserted IUD than the first IUD. Health workers must
      also be informed about the high probability of another expulsion when re
      inserting an IUD after an expulsion.

PMID- 8747045
TI  - Prospective randomized comparison of intrauterine and intracervical insemination
      with donor spermatozoa.
AB  - From March 1990 to September 1993, 20 women underwent a total of 89 cycles of
      intracervical inseminations with donor semen (ICI) and 23 women underwent 67
      cycles of intrauterine inseminations with donor semen (IUI). The women were
      assigned to the two groups randomly, but ensuring that the ages of the women and
      pathologies of the male partner (azoospermia or severe oligozoospermia) were
      similar in the two groups. There was no significant difference between the
      characteristics of the two groups and the method used to induce ovulation
      (HMG/HCG) was identical. Two semen straws were used for each insemination cycle.
      Semen was prepared for IUI on a Percoll gradient. Thirteen clinical pregnancies
      were obtained in the IUI group (19.4% of the attempts) and six in the ICI group
      (6.75%). After six cycles of insemination, 75.4% of the women of the IUI group
      obtained a pregnancy, as compared to 35% in the ICI group. These good results may
      be due to the method of induction of ovulation, but also to the technique itself,
      increasing the number of motile spermatozoa at the site of fertilization. The
      time taken to obtain a pregnancy is thus shorter with IUI than with ICI, and the
      number of semen straws required is smaller. In-vitro fertilization (IVF) should
      be proposed after six failures by IUI.

PMID- 8747046
TI  - CD4+ cells in human ejaculates.
AB  - Using flow cytometry, we studied the expression of the CD4 antigen within the
      different cells present in human ejaculate, both in spermatozoa and round cells.
      In all, 20 samples of semen were obtained from fertile males; in 11 of these, we
      detected the presence of leukocytes, using the peroxidase test. Swim-up was
      performed for the analysis of the spermatozoa. From our results it may be
      concluded that there is no expression of the CD4 antigen on the surface of human
      spermatozoa or on CD45- ejaculate cells (epithelial and germinal cells). However,
      we did detect the presence of the CD4 antigen on the surface of the leukocyte
      cells (CD45+). A better characterization of these CD45+ cells made it apparent
      that the CD4+ cells of ejaculate are composed of T lymphocytes (helper/inducer T
      lymphocytes) and monocytes. Thus we may conclude that human spermatozoa do not
      express the CD4 antigen, the cell surface receptor for human immunodeficiency
      virus. However, we did detect CD4+ T lymphocytes and CD4+ monocytes in semen.

PMID- 8747047
TI  - Definition of the optimal criteria for identifying hyperactivated human
      spermatozoa at 25 Hz using in-vitro fertilization as a functional end-point.
AB  - Spermatozoa from fertile donors were used to select and validate criteria for the
      automated classification of hyperactivated (HA) motility using a computer-aided
      sperm analysis (CASA) system operating at 25 Hz. In the first phase of this
      analysis, 710 sperm trajectories were analysed and classified as forward
      progressive (FP), transition phase (TP) or HA. These tracks were then subjected
      to a CASA analysis and the various attributes of sperm movement defined for each
      category of motion. From this analysis, criteria were identified and subsequently
      validated that permitted the automated selection of FP, TP+HA and HA cells, with
      > 90% accuracy. To determine which attributes of movement best predicted the
      fertilizing potential of human spermatozoa, a detailed analysis of sperm motion
      was undertaken in patients undergoing in-vitro fertilization therapy. This
      analysis indicated that the single most important aspect of sperm movement was
      the incidence of HA motility (defined as curvilinear velocity > 90 microns/s,
      linearity < 20%, dancemean [amplitude of lateral head displacement/linearity x
      100] > 45.8 microns) after 3 h of incubation. Using the latter criterion as the
      first incorporated variable, multiple regression equations were created that
      explained up to 50% of the variance in fertilization rates. None of the other
      patterns of motion (FP, TP, TP+HA) was correlated with fertilization rates, and
      none of the other published algorithms for identifying HA cells were as efficient
      as those described here.

PMID- 8747048
TI  - Thyroid autoantibodies in euthyroid non-pregnant women with recurrent spontaneous
      abortions.
AB  - This study was undertaken to evaluate the incidence of thyroid autoantibodies in
      women with a history of recurrent (three or more consecutive) spontaneous
      abortions. A total of 22 euthyroid non-pregnant habitual aborters were analysed
      for thyreoglobulin and thyroid peroxidase antibodies; 22 nulligravidae and 22
      multigravidae without endocrine dysfunction served as controls. Both thyroid
      antibodies were assayed using highly sensitive, commercially available enzyme
      linked immunosorbent assay kits. Eight of the 22 women with recurrent spontaneous
      abortions (36%) but only two of the 22 nulligravidae controls (9%; chi 2 test, P
      = 0.03) and one of 22 multigravidae subjects (5%; chi 2 test, P < 0.01)
      demonstrated positive titres (> 100 IU/ml, as recommended by the manufacturer) of
      thyreoglobulin, thyroid peroxidase or both antibodies. The mean +/- SD antibody
      concentrations were 102.5 +/- 226.5 in the study versus 20.9 +/- 68.8 in the
      nulligravidae (U-test, P = 0.057) and 26.4 +/- 60.2 IU/ml (P = 0.097) in the
      multigravidae population for thyroid peroxidase, and 47.7 +/- 57.9 versus 24.1 +/
      31.9 (U-test, P = 0.051) and 28.1 +/- 27.9 IU/ml (P = 0.059) for thyreoglobulin.
      In conclusion, the incidence of thyroid antibodies in euthyroid women with
      habitual abortions appears to be significantly increased compared with the
      controls of reproductive age without previous abortions. Although the important
      issue of cause and effect has not been fully clarified, this finding suggests
      that thyroid antibodies may be a marker for autoimmune-mediated recurrent
      spontaneous abortions, not dissimilar to, for example, anticardiolipin.

PMID- 8747049
TI  - Comparison of SUZI and ICSI for severe male factor.
AB  - We compare the results of subzonal insemination (SUZI) and intracytoplasmic sperm
      injection (ICSI) carried out between February 1993 and end of August 1994. A
      total of 232 couples underwent 302 cycles of micro-assisted fertilization (79
      patients had SUZI for a total of 93 cycles, 153 patients ICSI for a total of 209
      cycles). The indications for treatment were obstructive azoospermia in 35 cycles,
      ejaculatory failure with severely low sperm count in 7 cycles, and failure of
      fertilization in a previous IVF cycle or less than 10% of oocytes fertilized in
      87 cycles. In 173 cycles the indication for treatment was a poor semen parameter.
      Patients undergoing ICSI had significantly higher fertilization rates [43
      (728/1692) versus 22.3% (151/ 676), chi 2 = 86.308, P < 0.0001], better chances
      of embryo transfer [95 (199/209) versus 73% (68/93), chi 2 = 30.671, P < 0.001],
      and greater numbers of embryos transferred (2.4 +/- 0.9 versus 1.6 +/- 1.2 F =
      42, P < 0.0001) than patients who had SUZI. Eighteen patients became pregnant
      following the SUZI procedure, a pregnancy rate of 19% per egg collection,
      compared with 28% for those who underwent the ICSI procedure, where 58 out of 209
      became pregnant. The pregnancy rate was similar in those who underwent embryo
      transfer, whether they had ICSI or SUZI (29.2 and 28.6% respectively). Overall,
      the pregnancy rate doubled with each number of embryos transferred, so it was
      8.9% when one embryo was transferred, which increased to 18.3% when two embryos
      were transferred, and this rose to 37.7% when three embryos were transferred.
      There was no significant difference in the pregnancy wastage rate between SUZI
      and ICSI. None of the offspring from either SUZI or ICSI showed any evidence of
      fetal abnormalities. Pregnancy rate was negatively correlated, with sperm
      progression being 36% (36/100) if progression was < 2 and 19.8% (40/202) if it
      was > or = 2 (chi 2 = 8.99, P < .002). ICSI therefore provides a higher number of
      embryos available for transfer and should be the primary treatment for severe
      male factor infertility.

PMID- 8747050
TI  - Comparison of two methods to obtain hemizonae pellucidae for sperm function
      tests.
AB  - The development of a new generation of diagnostic techniques has provided
      objective data on the physiological function of the spermatozoon. The hemizona
      assay has been considered the best predictor for in-vitro fertilization results.
      Its clinical application has been limited to the availability of human oocytes
      and the use of a special micromanipulator. Here, the sperm binding capacity of
      hand-sectioned hemizonae was compared with that of oocytes bisected by a
      micromanipulator. The results obtained in parallel assays showed no statistical
      differences between the two methods. Therefore, the bisection of oocytes by hand
      is useful for hemizona assays even in normal clinical laboratories.

PMID- 8747051
TI  - Selection and characterization of human acrosome reacted spermatozoa.
AB  - In order to study the characteristics of human acrosome reacted spermatozoa, we
      developed a method to select them. Spermatozoa, obtained from 20 fertile
      volunteers, were selected by using GB24 antibody fixed on magnetic immunobeads,
      after acrosome reaction induced by 50% follicular fluid. Bead-bound spermatozoa
      were then detached using sheep anti-mouse IGG F(ab')2 antibody. This method
      allowed recovery of 170 +/- 48 x 10(3) spermatozoa (n = 20), free of GB24
      antibody, as assessed by incubation with FITC-rabbit anti-mouse antibody. The
      percentage of acrosome reacted spermatozoa in the selected population was 88 +/-
      3% versus 32 +/- 6% in the whole sperm population. Concerning sperm morphology,
      the percentage of head abnormalities was lowered (15 +/- 3% versus 20 +/- 3%).
      The motility of selected spermatozoa was dramatically reduced (7 +/- 3% versus 53
      +/- 7% in the whole population) despite no difference in viability (84 +/- 3%
      versus 80 +/- 4%). However, the viability after an 18 h incubation was very low
      (1 +/- 0.5% versus 46 +/- 5%). These results show that acrosome reaction occurs
      in the most morphologically normal spermatozoa and is followed by a loss in
      motility and a decrease in longevity.

PMID- 8747052
TI  - Relationship between an asymptomatic male genital tract exposure to Chlamydia
      trachomatis and an autoimmune response to spermatozoa.
AB  - The relationship between a localized genital tract humoral immune response to
      Chlamydia trachomatis and the presence of antisperm antibodies on the surface of
      motile spermatozoa in the ejaculate was examined in 227 asymptomatic male
      partners of infertile couples with no history of exposure to C.trachomatis. Semen
      and serum samples were assayed for immunoglobulin (Ig) A and IgG antibodies to
      C.trachomatis by enzyme-linked immunosorbent assay employing a recombinant
      Chlamydia-specific lipopolysaccharide fragment (Medac, Hamburg, Germany), while
      motile spermatozoa were tested for bound autoantibodies by immunobead binding.
      Semen samples from 24.7 and 10.9% of the men were positive for IgA and IgG
      antibodies to C.trachomatis respectively. In comparison, antichlamydial IgA was
      less prevalent in sera (14.5%) than in semen (P = 0.01), while antichlamydial IgG
      was most prevalent (21.5%) in sera (P = 0.003). In 75.0% of the men with
      antichlamydial IgA in their semen, this antibody was undetectable in sera
      obtained at the time of semen collection. Conversely, 84.0% of the men with
      seminal antichlamydial IgG were also IgG seropositive. Antisperm IgG and/or IgA
      were detected on motile spermatozoa from 16.3% of the men; their occurrence was
      strongly correlated with the presence of antichlamydial IgA in semen (P <
      0.0001). Weaker associations between antisperm antibodies and either seminal IgG
      antibodies to C.trachomatis (P = 0.01) or circulating IgA and IgG antichlamydial
      antibodies (P = 0.03) were also observed. Men with antichlamydial IgA in their
      semen had a lower median sperm count (82 versus 144 x 10(6)/ml) than those men
      without (P = 0.003); sperm morphology and motility were comparable in both
      groups. These data suggest that asymptomatic male genital tract exposure to
      C.trachomatis is a frequent event among this population and that the presence of
      a humoral immune response to this organism is correlated with the development of
      an autoimmune response to spermatozoa.

PMID- 8747053
TI  - Comparison of four mechanical methods to retrieve spermatozoa from testicular
      tissue.
AB  - To maximize the total number of spermatozoa which can be retrieved from a
      testicular biopsy, four mechanical methods for preparation were compared. In all,
      17 biopsies were divided into four equal fractions, which were weighed
      individually and prepared by rough shredding (control), fine mincing, vortexing
      and crushing (electrical Potter). After resuspension in an erythrocyte-lysing
      buffer, removal of the remaining tissue pieces, washing and centrifugation, the
      following parameters were evaluated: number of spermatozoa per 100 mg tissue,
      percentage motility, percentage vitality and percentage normal morphology (strict
      Kruger criteria). After further purification by discontinuous Percoll
      centrifugation, the same parameters were assessed again. This procedure was
      efficient in obtaining only spermatozoa in the final fraction. Before Percoll
      centrifugation, only minor differences between methods were observed. Percoll
      centrifugation generally resulted in a pronounced loss of sperm cells, partly
      because of the abnormal dimensions of the eliminated cells. After Percoll
      centrifugation, treatment of the testicular tissue by fine mincing was the most
      effective method in terms of the total number of motile spermatozoa and
      percentage normal morphology.

PMID- 8747054
TI  - Sperm plasma membrane damage prior to intracytoplasmic sperm injection: a
      necessary condition for sperm nucleus decondensation.
AB  - In the present study we investigated the relevance of sperm immobilization prior
      to intracytoplasmic sperm injection (ICSI) in the fertilization process. Using
      supravital staining of the spermatozoa with eosin and studying sperm
      decondensation with 2 mM dithiothreitol (DTT) in conditions imitating sperm
      handling during ICSI, we demonstrated that immobilization of the spermatozoon by
      squeezing its tail between the glass pipette and the bottom of the dish damages
      the sperm plasma membrane. Polyvinylpyrrolidone (PVP), which is usually present
      in the drop with the spermatozoon to facilitate its handling, was found to impede
      the access of both eosin and DTT to the sperm nucleus. We conclude that (i) sperm
      immobilization prior to ICSI damages the sperm plasma membrane, that (ii) this
      damage is sufficient for thiol-reducing agents to gain access to the sperm
      nucleus, and finally that (iii) PVP possibly interferes with sperm nucleus
      decondensation.

PMID- 8747055
TI  - Recovery of ovarian function after laparoscopic detorsion.
AB  - In an attempt to preserve ovarian function, we managed 58 women with adnexal
      torsion by laparoscopic detorsion. Follow-up ultrasound examinations were
      performed on 54 of the women. Follicular development was evident in 49 of 52
      (94.2%) women with normal-sized ovaries. We conclude that ovarian function
      returns in the majority of women with adnexal torsion managed conservatively.

PMID- 8747056
TI  - A paradoxical inhibition of androgenic hyperproduction by a Sertoli-Leydig cell
      tumour ovary.
AB  - A 17 year old woman was evaluated for amenorrhoea and severe hirsutism (Ferriman
      Gallway index = 31). Pelvic ultrasound demonstrated a right unilateral ovarian
      mass (6 x 5 cm), whereas the computed tomography for the adrenal gland was
      normal. Endocrinological findings revealed normal concentrations of oestradiol,
      progesterone, dihydroepiandrosterone sulphate, cortisol, prolactin, follicle
      stimulating hormone, luteinizing hormone and adrenocorticotrophic hormone (ACTH).
      Total testosterone, free testosterone, androstenedione and 17-hydroxy
      progesterone concentrations, already elevated at basal conditions, did not
      increase after an ACTH test, whereas they decreased significantly after
      dexamethasone administration and increased after a human chorionic gonadotrophin
      test. Of all the tumour markers investigated, tissue polypeptide antigen and
      alpha 1-fetoprotein showed an increase in concentration. Selective venous ovarian
      catheterization indicated the presence of an androgen-producing tumour in the
      right ovary. The histopathological diagnosis was consistent with a Sertoli-Leydig
      cell tumour ranking between an intermediate and a poor grade of differentiation,
      with heterologous elements characterized by mucinous epithelium of the gastro
      intestinal type. An endocrine evaluation performed postoperatively showed a
      normalization of all serum pathological hormones and tumour markers studied. Some
      particular aspects were focused on and discussed.

PMID- 8747057
TI  - A comparative analysis of embryos derived from routine in-vitro fertilization and
      subzonal microinsemination.
AB  - Embryos obtained from patients undergoing routine in-vitro fertilization (IVF)
      and embryo transfer were compared with those undergoing subzonal
      microinsemination (SUZI) for male factor infertility. Overall, the proportion of
      cleaved embryos was significantly higher in the IVF group in comparison with the
      SUZI group at 48 h post-insemination [1533 out of 1609 (95.3%) versus 776 out of
      952 (81.5%)]. The mean +/- SD grading score of the IVF-derived embryos of 3.61 +/
      0.50 was significantly better than that for SUZI of 2.97 +/- 0.86 (P < 0.0005)
      at the same time. The implantation rates following the replacement of IVF or SUZI
      embryos at 48 h were comparable: 14.3 and 10.0% respectively. However, the IVF
      embryo implantation rate of 15.1% at 72 h was significantly better than that
      following the replacement of SUZI embryos at either 48 (10.0%) or 72 h (8.0%).
      The replacement of SUZI-derived embryos at 48 h resulted in significantly higher
      pregnancy (25.0%) and implantation rates (10.0%) than at 72 h, with rates of 10.8
      and 8.0% respectively. Similarly, the overall embryo quality deteriorated
      following in-vitro culture for up to 72 h. The clinical pregnancy loss rate
      (33.0%) was highest following the replacement of SUZI embryos at 72 h, although
      the data were limited. It is suggested that these data indicate that a
      combination of in-vitro manipulation, the injection of multiple spermatozoa into
      the subzonal space and probably the genomic capacity of spermatozoa derived from
      poor-quality semen may contribute to the poorer outcome of embryo development
      following SUZI. Prolonged in-vitro culture beyond 48 h appears to be deleterious
      to the development of SUZI cleaved embryos and the subsequent outcome of
      treatment, and hence should be avoided.

PMID- 8747058
TI  - A retrospective analysis of the in-vitro development of 'spare' human in-vitro
      fertilization preimplantation embryos using 'in-house' prepared medium and 'Medi
      Cult' commercial medium.
AB  - In-house prepared medium was used routinely in our in-vitro fertilization (IVF)
      facility prior to the introduction of the commercial 'Medi-Cult' products. A
      comparative study of the in-vitro development of embryos cultured in two [T6 and
      Earle's balanced salt solution (EBSS)] human-inactivated serum (HIS)-supplemented
      media from days 0 to 5 showed that 44.7% (46/103) of the embryos developed to the
      blastocyst stage in the T6 medium compared with 22.3% (23/103) in EBSS. Following
      the introduction of the commercial Medi-Cult IVF M2 medium, which is used
      routinely to culture fertilized eggs from days 0 to 2, new baseline data were
      required for the in-vitro development of 'spare' embryos from days 2 to 5. When
      Medi-Cult M3 medium was used, 35.6% (37/104) of the 'spare' day 2 embryos
      achieved the blastocyst stage. However, if morphologically similar (four normal
      nucleated blastomeres with no fragmentation) day 2 embryos were selected, an
      increase in the blastocyst rate to 50.0% (33/66) was achieved. This compared
      favourably with the 45.0% blastocyst rate (published in the Medi-Cult literature)
      for M2/M3 medium cultured human embryos. A small series of experiments with T6 +
      HIS medium and human serum albumin (HSA)-supplemented Ham's F-10, MCDB 302 and M3
      media was undertaken to identify a suitable medium which could be used for the
      culture of M2 medium day 2 embryos. Results show that M2 medium cultured embryos
      placed in Ham's F-10 medium supplemented with 10 mg/ml HSA gave an acceptable
      37.8% (14/45) blastocyst rate. Therefore, this medium could be substituted for M3
      medium in an emergency. A total of 483 IVF embryos donated by patients, which
      were surplus to the therapeutic IVF programme, were used for these studies over a
      period of 30 months. Late day 2 IVF spare embryos were assigned an embryo score
      based on a high-power phase-contrast microscopic examination prior to being
      placed in culture. The embryo score provides an effective in-vitro parameter with
      which embryos from different patients can be compared. The cleavage and
      development of individual embryos were monitored on days 2 to 5. In some cases,
      the continuing normal development and viability of the day 5 cultured embryo were
      assessed by monitoring the hatching, attachment and outgrowth of the cavitated
      blastocyst.

PMID- 8747059
TI  - Effects of amino acids on the development of in-vitro matured/in-vitro
      fertilization bovine embryos in a simple protein-free medium.
AB  - The effects of commercially available amino acids, referred to as Eagle's non
      essential amino acids (NEAA) and essential amino acids (EAA), on the development
      of bovine embryos produced by in-vitro maturation and in-vitro fertilization
      (IVF) in a simple modified protein-free KSOM medium containing polyvinyl alcohol
      (PVA) were studied. Embryos produced by IVF were cultured in an atmosphere of 5%
      O2, 5% CO2 and 90% N2 at 39 degrees C for the first 40-44 h in modified KSOM.
      Then embryos with four or more cells were cultured in modified KSOM-PVA with
      different amino acids for another 6 days in experiments 1 and 2. In experiment 3,
      to study embryo hatching and degeneration further as criteria of medium
      suitability, the culture time was 8 days. In experiment 1, more blastocysts were
      produced (P < 0.05) in the medium with 0.5 x NEAA (37%) than with 0.25 or 0.5 x
      EAA (both 15%). In experiment 2, when 0.0, 0.5 and 1.0 x concentrations of NEAA
      were combined with 0.0 and 0.5 x concentrations of EAA, the combination 1.0 x
      NEAA with 0.5 x EAA resulted in the most blastocysts (39%), with 11% hatching (P
      < 0.05). Without NEAA, 1.0 x EAA resulted in 6% blastocysts (P < 0.05). In
      experiment 3, KSOM-PVA with 1.0 x NEAA plus 0.5 x EAA resulted in 41%
      blastocysts, similar to the 40% blastocysts in KSOM-bovine serum albumin (BSA)
      with the same amino acids added. When culture was continued for 2 more days, more
      embryos hatched in these two treatments. These results indicate that the
      combination of 1.0 x NEAA with 0.5 x EAA promoted blastocyst formation and
      hatching, but EAA alone was detrimental. With PVA successfully replacing BSA, a
      completely defined medium resulted, which was equal or superior to complex
      medium, and is potentially useful for the culture of embryos from other species,
      such as humans.

PMID- 8747060
TI  - Sex selection may be inadvertently performed in in-vitro fertilization-embryo
      transfer programmes.
AB  - The present study aims to ascertain whether sex selection may be inadvertently
      performed in human in-vitro fertilization (IVF) and embryo transfer (IVF-embryo
      transfer) programmes when selecting for high quality embryos (those with the
      fastest cleaving rates and/or the best morphology) at the fresh transfer cycle.
      All patients entering into the study were treated with gonadotrophins after
      pituitary suppression with gonadotrophin-releasing hormone agonists (GnRHa) and
      had intrauterine embryo transfer on day 2 post-insemination. These patients were
      retrospectively divided into three groups according to whether the difference in
      mean number of cells between embryos transferred and all embryos available for
      transfer in a given cycle was less than (negative selection), equal to (no
      selection) or greater (positive selection) than zero. In cycles resulting in
      singleton births, the sex ratio of the resulting babies was significantly (P < or
      = 0.005) shifted toward the female (88.8%) and to the male (90.0%) in the
      negative and positive selection groups respectively. No shift in sex ratio was
      observed in cycles resulting in multiple births. Maternal age was another
      independent factor affecting sex ratio at birth. Sex ratio was significantly (P <
      or = 0.05) skewed in favour of males (62.7%) and females (71.4%) in women < 35
      and > or = 35 years of age respectively. Maternal age, number of embryos
      transferred and the event of selecting or not selecting the slowest cleaving
      embryos for transfer were entered automatically in a three-group discriminant
      model for distinguishing cycles resulting in only boys, both boys and girls, and
      only girls. These data suggest that (i) sex selection may be inadvertently
      performed in IVF-embryo transfer programmes when selecting for high quality
      embryos at the fresh transfer cycles; (ii) human endometria may be favourable,
      indifferent or hostile to either fast cleaving or slow cleaving embryos depending
      on maternal age; and (iii) "natural' sex selection may be performed for social,
      psychological or medical reasons.

PMID- 8747061
TI  - Prospective evaluation of simple morphological criteria for embryo selection in
      double embryo transfer cycles.
AB  - Preventing the occurrence of high-rank multiple pregnancies without reducing the
      pregnancy rate remains a high priority of in-vitro fertilization and embryo
      transfer programmes. Our previous study demonstrated that, if there is at least
      one embryo with a good morphological grade, then the transfer of two (a double
      embryo transfer) instead of three embryos does not result in a lower pregnancy
      rate, and that the influence of the number of embryos transferred becomes
      significant only when poor-quality embryos are transferred. This result allowed
      us to employ the simple policy of systematically selecting double embryo transfer
      cycles without affecting the pregnancy rate. Since January 1994, when patients <
      37 years of age had more than two embryos available for transfer, only two
      instead of three embryos were transferred if at least one of the embryos
      demonstrated a good morphological grade. After a 1 year application of this
      policy, of the 147 cycles (group A) that fulfilled the above criteria, two
      embryos were transferred in 92 cycles, while three embryos were transferred in
      the other 55 cycles. The results of these cycles were compared to those of the
      control 144 cycles (group B) in which three embryos were transferred, prior to
      the application of this policy. The on-going pregnancy rates and the incidence of
      multiple and triplet pregnancies were 24% and 28%, 22% and 23%, and 2% and 9% in
      groups A and B respectively. The rates were not significantly different. In
      conclusion, although our prospective trial demonstrated a tendency of decreasing
      pregnancy rate and an invariable incidence of multiple pregnancies, the very low
      occurrence of triplets during this period indicated that this policy provided a
      practical compromise between achieving a high pregnancy rate and an acceptable
      incidence of triplet pregnancies.

PMID- 8747062
TI  - Morphology and biochemistry of in-vitro produced bovine embryos: implications for
      their cryopreservation.
AB  - Examination of some ultrastructural and physiological characteristics of in-vitro
      produced bovine embryos may help to explain why such embryos are more sensitive
      to freezing than their in-vivo derived counterparts. Improvement of embryo
      survival after freezing can be achieved by changing the conditions of their
      culture, selection of embryos based on the kinetics of their development, and
      changing "standard' freezing procedures. Cryopreservation of embryos by
      vitrification, in particular, seems to yield higher survival than conventional
      slow freezing. Further development of protocols requires additional embryo
      transfer studies to ensure that the ability of thawed embryos to develop normally
      in vivo correlates strongly with in-vitro survival assays.

PMID- 8747063
TI  - Timing of sperm and oocyte nuclear progression after intracytoplasmic sperm
      injection.
AB  - We investigated the time course of human oocyte activation after intracytoplasmic
      sperm injection (ICSI) by observing the oocyte chromosome configuration at
      different times after injection. One day old human oocytes were injected with
      spermatozoa and subjected to cytogenetic analysis at 2, 3, 4 and 5 h after
      injection. We found that anaphase is initiated in the vast majority of the
      oocytes between 2 and 3 h after injection, and that by 4-5 h after injection most
      of the oocytes have reached the chromatin mass stage. Two distinguishable stages
      of sperm nucleus transformation were observed. The first phase-swelling-was
      reached within 2 h after the injection and was independent of oocyte activation.
      The second phase-the "brush'-like stage or decondensed chromatin stage-was found
      only in activated oocytes. Moreover, this stage was not reached before the
      chromatin mass stage (late telophase) of the oocyte. The same proportion of
      metaphase II oocyte chromosome configurations and unchanged sperm nuclei was
      found at any given time after injection. We conclude that: (i) ICSI allows users
      to obtain an almost synchronized population of activated oocytes; (ii) anaphase
      II is initiated in the majority of oocytes not later than 2-3 h after injection
      and telophase II is reached approximately 5 h after injection; and (iii) there
      are two distinguishable phases of sperm nucleus transformation after ICSI: oocyte
      activation-independent swelling of the sperm head and oocyte activation-dependent
      chromatin decondensation which is coupled to the beginning of oocyte chromosome
      decondensation.

PMID- 8747064
TI  - Improvement of pregnancy and implantation rates in cyclic women undergoing oocyte
      donation after long-term down-regulation.
AB  - An oocyte donation programme was carried out in 122 patients aged between 40 and
      49 years for a total of 225 replacement cycles. Eggs were donated by 103 women
      undergoing assisted reproduction technologies in our infertility centre.
      Recipients were divided into different groups according to whether they were
      menopausal (group A) or cyclic and treated with short- (group B) or long-term
      (group C) gonadotrophin-releasing hormone analogues. In group C, the ovarian
      suppression of the patients was prolonged with the aim of producing a type of
      artificial menopause. Oocyte donors were aged between 21 and 35 years, and were
      equally distributed between the different groups. There were significant
      differences in pregnancy and implantation rates according to ovarian status: 30.8
      and 16.1% respectively in group A, 30.6 and 17.7% respectively in group C versus
      10.4 and 5.6% respectively in group B. Apart from improved pregnancy and
      implantation rates in cyclic women aged > 40 years after long-term down
      regulation, these data seem to demonstrate an important role for the endometrium
      in the implantation process.

PMID- 8747065
TI  - Evaluation of the mechanism for higher pregnancy rates in donor oocyte recipients
      by comparison of fresh with frozen embryo transfer pregnancy rates in a shared
      oocyte programme.
AB  - The objective of this study was to determine the mechanism for higher pregnancy
      rates in oocyte recipients by comparing the pregnancy rates following fresh and
      frozen embryo transfers in a shared oocyte programme. A prospective study was
      carried out of 135 matched pairs of donors and recipients who equally share the
      donors' pool of oocytes. Recipients were subclassified by ovarian function: 69
      were in ovarian failure and 66 retained ovarian function. A total of 474 standard
      in-vitro fertilization cycles using the same ovarian stimulation protocol as the
      donors were also evaluated. The main outcome measures were the clinical pregnancy
      and implantation rates for donors and recipients following fresh and frozen
      embryo transfers. The clinical pregnancy rates per transfer for fresh embryo
      transfers were 17.5% for donors, 20.4% for recipients with ovarian function and
      46.3% for recipients in ovarian failure (P < 0.05). The pregnancy rates for
      frozen embryo transfers were 15.3% for donors, 17.2% for recipients with ovarian
      function and 23.8% for recipients in ovarian failure (not significantly
      different). The implantation rates for fresh transfers were 7.5% for donors, 8.6%
      for recipients with ovarian function and 15.6% for recipients in ovarian failure
      (P < 0.05); for frozen cycles, the implantation rates were 5.1, 5.2 and 7.1%
      respectively (not significantly different). When classified by age and ovarian
      function, the clinical pregnancy rates per transfer for recipients with ovarian
      function were 14.0% for those aged > or = 40 and 22.2% for those aged < 40 years.
      For recipients in ovarian failure, the pregnancy rates were 33.3% for the older
      group of women and 39.4% for the younger group. A logistic regression analysis
      found that ovarian function was the only factor to have an independent effect on
      outcome. The demonstration of higher pregnancy and implantation rates in
      recipients versus donors following fresh embryo transfer, despite the use of a
      common pool of oocytes, strongly suggests that the well-known higher fecundity
      found in recipients is not predominantly related to the use of better quality
      oocytes. The demonstration of an implantation rate twice as high following fresh
      versus frozen embryo transfer in recipients with ovarian failure suggests that
      the frozen embryo is not as hardy as the fresh embryo. Thus, the fact that both
      the pregnancy and implantation rates in donors were the same with fresh versus
      frozen embryo transfer suggests that the ovarian stimulation regimen has a
      negative effect on outcome. However, the clear demonstration of higher pregnancy
      rates in recipients with ovarian failure compared with those with ovarian
      function suggests that, in addition, these higher rates may be linked to a
      superior uterine environment in patients with ovarian failure. Alternatively, the
      use of gonadotrophin-releasing hormone agonists may have a negative effect on
      implantation in patients with ovarian function.

PMID- 8747066
TI  - Endometrial stromal cell decidualization inhibits human chorionic gonadotrophin
      and human placental lactogen secretion by co-cultured trophoblasts.
AB  - We have developed an in-vitro co-culture system to examine the interaction
      between purified first trimester cytotrophoblasts and purified non-pregnant human
      endometrial stromal cells (ESC). ESC decidualization is an important step in
      endometrial maturation and may modulate embryo implantation. In order to
      investigate the effects of ESC decidualization on trophoblast function, we
      examined human chorionic gonadotrophin (HCG), human placental lactogen (HPL),
      progesterone and estrogen secretion by trophoblasts co-cultured in contact with
      ESC, either with or without decidualization induced by progesterone. Decidualized
      ESC inhibited basal HCG and HPL secretion for 3 days during the culture for HCG,
      and for 5 days during the culture for HPL (P < 0.01 and P < 0.03 respectively).
      After 5 days of co-culture, decidual transformation of ESC as indicated by
      prolactin production occurred in the control cultures due to progesterone and
      oestradiol secretion by the co-cultured trophoblasts, but no significant
      differences in HCG or HPL secretion were observed between the two groups.
      Although the type of trophoblast used in the present study is far from
      implantation, our results clearly demonstrated that HCG and HPL secretion by
      trophoblasts was inhibited by the presence of co-cultured decidualized ESC, and
      suggested that ESC decidualization may regulate trophoblast function at the human
      fetal-maternal interface.

PMID- 8747067
TI  - The probability of pregnancy after embryo transfer is affected by the age of the
      patient, cause of infertility, number of embryos transferred and the average
      morphology score, as revealed by multiple logistic regression analysis.
AB  - Because the process of conception is affected by many variables, a multiple
      logistic regression analysis was performed to assess (i) the impact and relative
      weight of both patient and embryo variables and (ii) their possible effects on
      the probability of a vital pregnancy after embryo transfer. A statistical model
      was constructed predicting the probability of pregnancy after embryo transfer.
      The variables that contributed significantly to the predictive value of the model
      were the age of the patient, the cause of infertility, the number of embryos
      transferred and the average morphology score of the transferred embryos. Embryo
      variables appeared to have a significant but modest value in predicting the
      probability of pregnancy after embryo transfer. Other variables, such as the
      thickness of the endometrium, were found to have no prognostic value. Moreover,
      we found that their effect could be explained by the variables already included
      in the model.

PMID- 8747068
TI  - Are 'natural' twinning rates continuing to decline?
AB  - During the 1960s and 1970s, the maternal age-specific twinning rates were
      declining in England and Wales and many other countries. However, around 1980
      this change reversed and since then twinning rates have been increasing. The
      question arises whether this increase is simply a consequence of hormonal
      induction of ovulation and various other techniques of assisted reproduction. The
      question assumes some importance because the level of "natural' twinning may be
      an index of reproductive (and other) health. Nationwide data on the prevalence of
      medically assisted conceptions are not available, so indirect methods have to be
      used to answer the question. It is tentatively concluded here that the "natural'
      twinning rate has recently been increasing in England and Wales and Belgium.
      These conclusions are based on two assumptions: (i) that in England and Wales,
      conceptions by young women are infrequently preceded by medical assistance; and
      (ii) in Belgium, the rate of medically assisted conceptions is not lower in East
      Flanders than in the rest of Belgium. Direct data on these points would test
      these conclusions.

PMID- 8747069
TI  - Morphometric analysis of the great vessels in early fetal life.
AB  - Pathological examination of the heart and great vessels was performed in 61
      specimens obtained after surgical termination of pregnancy for psychosocial
      indications at 9-18 weeks of gestation. The aorta and pulmonary trunk were
      identified and external diameters were measured at the level of, and distal to
      the aortic valve and pulmonary valve, the level of the aortic isthmus and
      thoracic aorta, and the proximal and distal ductus arteriosus. All eight vessel
      diameters increased linearly with gestational age and the ratio of the diameter
      of the aortic isthmus to that of the aortic valve or the distal ductus arteriosus
      also increased with gestation. Early pregnancy is characterized by rapid growth
      of the fetal head and this may well be the consequence of a preferential
      distribution of left ventricular output in favour of the head due to relative
      narrowing of the aortic isthmus at this gestation.

PMID- 8747070
TI  - Increased nuchal translucency in trisomy 21 fetuses: relationship to narrowing of
      the aortic isthmus.
AB  - Pathological examination of the great vessels was performed in 34 trisomy 21
      fetuses after surgical termination of pregnancy at 11-16 weeks of gestation. In
      each case, the external diameters of eight segments of the great vessels were
      measured. The aortic valve and the ascending aorta were wider than in normal
      fetuses, whilst the aortic isthmus was narrower. The degree of narrowing of the
      isthmus was significantly greater in fetuses with high nuchal translucency
      thickness and it is possible that there is a causal association between the two.

PMID- 8747071
TI  - The effect of an in-vitro fertilization pregnancy on a woman with genital
      tuberculosis.
AB  - The coexistence of an in-vitro fertilization (IVF) pregnancy and genital
      tuberculosis may pose life-threatening consequences. This case report describes
      catastrophic dissemination of latent genital tuberculosis, followed by IVF and
      pregnancy. The role of both IVF manipulation and the pregnancy itself in the
      exacerbation of latent tuberculosis is discussed. In addition, some measures for
      the detection, follow-up and treatment of latent genital tuberculosis in patients
      who undergo IVF are proposed.

PMID- 8747072
TI  - Fetal congenital abnormality (thanatophoric dwarfism) in one of two simultaneous
      recipients from a single altruistic ovum donor.

PMID- 8747073
TI  - Recurrent maternal virilization during pregnancy associated with polycystic
      ovarian syndrome: a case report and review of the literature.
AB  - Maternal virilization in pregnancy is associated, in most benign cases, with
      luteoma of pregnancy and hyperreactio luteinalis. Only a few reports relate this
      phenomenon to hyperthecosis or polycystic ovarian syndrome (PCOS). A case of
      recurrent maternal virilization during two consecutive pregnancies in a patient
      with PCOS is presented. In both pregnancies, the deepening of her voice, facial
      hirsutism and scalp hair loss began at the end of the first trimester and
      regressed 3-4 months post-partum. The patient underwent ovarian venous
      catheterization, and androgen secretion from both ovaries was found to be
      markedly high but similar, therefore ruling out an ovarian androgen-secreting
      tumour. Reviewing the English literature of similar cases, we found reports of
      only seven cases of maternal virilization during pregnancy associated with PCOS.
      Here, we present a case of recurrent maternal virilization in pregnancy
      associated with PCOS.

PMID- 8747074
TI  - Continuation of a donor oocyte pregnancy in a functionally agonadal patient
      without early oestrogen support.
AB  - A 40 year old functionally agonadal patient was the recipient of fertilized
      donated oocytes. She accidentally discontinued all oestrogen support on the day
      preceding embryo transfer until it was reinstated 12 days later. However, a
      pregnancy was established and resulted in the birth of healthy normal twin
      infants. This case report suggests that minimal amounts, if any, of oestradiol
      are sufficient to maintain an early pregnancy, provided adequate amounts of
      progesterone are given. This is consistent with a recent study conducted in
      subhuman primates.

PMID- 8747075
TI  - Monozygotic triplet pregnancy following transfer of frozen-thawed embryos.
AB  - We report a case of monozygotic triplet pregnancy after the transfer of three
      frozen-thawed embryos. The outcome of the pregnancy was the birth of three
      healthy normal boys. The pregnancy was a monochorionic triamniotic triplet
      pregnancy. This is the first such case of triplets, although it seems that zygote
      splitting is significantly more common than normal in patients undergoing in
      vitro fertilization.

PMID- 8747076
TI  - Intrauterine light delivery for photodynamic therapy of the human endometrium.
AB  - Photodynamic therapy is currently being evaluated as a minimally invasive
      procedure for endometrial ablation not requiring anaesthesia. Light penetration
      depths at 630, 660 and 690 nm and the optimal configuration of intrauterine light
      diffusing fibres were determined in 14 human uteri to assist in the design of a
      light intrauterine device. Post-menopausal ex-vivo uteri showed a significantly
      lower light penetration depth than pre-menopausal uteri. With a single central
      diffusing fibre inserted, the fluence rate measured in the uterine wall at the
      most remote point of the cavity decreased to 1.1 +/- 0.4% of that measured at
      closest proximity, whereas it decreased to only 40.0 +/- 9.0% with three fibres.
      Distension of the uterine cavity with 2 ml of an optically clear fluid increased
      the fluence rate at the fundus between the fibres at a depth of 2 mm by a factor
      of 4. We conclude that in normal-sized pre-menopausal uterine cavities, three
      diffusing fibres will deliver an optical dose above the photodynamic threshold
      level at a depth of 4 mm, even in the most remote areas, in < 30 min without
      causing thermal damage. For distorted and elongated cavities, either slight
      distension of the cavity or the insertion of a fourth diffusing fibre is
      required.

PMID- 8747077
TI  - Follow-up study of Finnish volunteer oocyte donors concerning their attitudes to
      oocyte donation.
AB  - A questionnaire was sent to the first 30 Finnish volunteer oocyte donors at 12-18
      months after donation to determine their experiences concerning treatment and
      attitudes to donation. All donations were carried out anonymously and without
      payment. The donors were recruited by advertising in newspapers. Most donors were
      very satisfied with the experience. The side-effects of the treatment had been
      slight and tolerable. In all, 85% of the respondents reported no gynaecological
      problems afterwards. The problems reported by the other 15% were minor and
      unrelated to the donation. A total of 67% of the respondents would have liked to
      have known if pregnancy had been achieved in the recipient, and 89% reported that
      they had thought about the possibility of a child from their donation. Some 42%
      of the respondents preferred to receive no information concerning either the
      child or the recipient couple. Of the respondents, 59% thought the offspring
      should be told about its origin and 33% thought the child should be given
      identifying information about the donor. About half of the others would agree to
      the release of non-identifying information. In all, 96% of the respondents
      reported that their own feelings were sufficiently taken into consideration
      during the treatment and 78% would donate again. No-one regretted their donation.

PMID- 8747078
TI  - Low-dose aspirin and recurrent miscarriage.

PMID- 8747079
TI  - Cyst formation.

PMID- 8747080
TI  - Biological markers in inflammatory rheumatic diseases.
AB  - Biological markers of inflammation are useful for the diagnosis and the
      monitoring of inflammatory rheumatisms and connective tissue diseases. These
      markers are not specific, and often poorly correlate with the long term evolution
      of the disease. C-reactive protein (CRP) is a sensitive marker, and is used to
      monitor inflammatory and infectious diseases. In rheumatoid arthritis (RA), CRP
      correlates with disease activity and response to therapy, and CRP levels are
      influenced by disease-modifying drugs and corticosteroids. Serum amyloid A (SAA)
      is another acute phase protein (APP) which appears in RA as a more sensitive
      marker than CRP. Several antinuclear antibodies serve as markers of systemic
      disorders; they are not implicated in the disease by themselves, but their
      production could be related to the genetic background underlying the pathogenesis
      of the disease. In systemic lupus erythematosus (SLE), the titer of anti-ds DNA
      antibodies often correlates with disease activity. DNA is poorly immunogenic and
      the production of anti-ds DNA antibodies could be linked to the association of
      DNA with more immunogenic protein antigens. Cellular DNA is associated with
      proteins in nucleosomes and it now appears more appropriate to consider the anti
      DNA antibody production as a response to a DNA-protein complex. Antibodies can be
      directed to histones and DNA-protein complexes such as transcription or
      replication complexes. Antibodies to ribonuclear proteins are associated with
      different disease subsets and help to define the prognosis in SLE and connective
      tissue diseases. The identification of antibodies directed against proteins and
      RNA components is still a field of research.

PMID- 8747081
TI  - 5 alpha-reductase activity in cultured epithelial and stromal cells from normal
      and hyperplastic human prostates--effect of finasteride (Proscar), a 5 alpha
      reductase inhibitor.
AB  - Benign prostatic hyperplasia (BPH) is the most common benign proliferative
      disorder of unknown etiology found in men. Dysregulation of testosterone
      conversion to dihydrotestosterone (DHT) by 5 alpha-reductase has been described
      as a key step in the development of BPH. We investigated the 5 alpha-reductase
      activity in primary cultures of epithelial and stromal cells from the four
      different regions (periurethral, transition, central and peripheral zones) of
      normal and hyperplastic human prostates. No significant difference in DHT
      production was observed among the four epithelial zones and the hyperplastic
      epithelial cells, or among the four normal zones and the hyperplastic stromal
      cells. To investigate whether the two known 5 alpha-reductase isoenzymes were
      expressed in prostate, we performed specific enzymatic amplification after
      reverse transcription which showed the presence of 274 and 383 base-pair
      fragments, respectively, specific for 5 alpha-reductase type 1 and 5 alpha
      reductase type 2, demonstrating the expression of mRNA for both isoenzymes in BPH
      tissue. To pharmacologically characterize the isoenzyme present in the two cell
      components of hyperplastic prostate, we used finasteride, a well known inhibitor
      specific to 5 alpha-reductase type 2, which only slightly inhibits 5 alpha
      reductase type 1. In BPH, IC50 was estimated at 62 nM and 45 nM, for stromal and
      epithelial cells respectively, suggesting predominately 5 alpha-reductase type 2
      activity. Our results provide further evidence that 5 alpha-reductase type 2
      activity is mainly responsible for DHT production by human prostatic cells.

PMID- 8747082
TI  - Presence of human papilloma virus in transitional cell carcinoma in Jewish
      population in Israel.
AB  - The possible causal association of human papilloma virus (HPV) with transitional
      cell carcinoma (TCC) of the urinary bladder in Israeli Jewish patients was
      assessed. One hundred and ten histopathological TCC sections were examined by
      peroxidase anti-peroxidase (PAP) method. HPV capsid antigen was demonstrated in
      19 out of 110 cases (17.3%). HPV-DNA sequences, determined by in situ DNA-DNA
      hybridization at high stringency wash were present in 24 cases (21.8%): 16(14.5%)
      cases proved to be HPV6/11 and 8 (7.3%) were HPV 16/18 positive. Four (3.6%) of
      the HPV 6/11 positive specimens cross hybridized with HPV 31/33/35 at low
      stringency conditions. Sixteen samples known to be positive by in situ
      hybridization were reconfirmed by polymerase chain reaction (PCR). When the PCR
      was performed on the 43 negative cases, an additional 4(9.3%) HPV positive cases
      were revealed: two proved to be HPV 6/11 and two HPV 16/18. Comparison of the
      different methods for HPV detection in 59 TCC histopathological samples, showed
      good correlation; an overall positivity of 33.9% by PCR, 27.1% by in situ
      hybridization and 25.4% by PAP was observed. Forty one samples from nontumoral
      material of the bladder or post mortem specimens served as controls and 4.8% HPV
      DNA was present in only two cases: one HPV 6/11 and one 16/18. Hence, HPV in TCC
      of the bladder is detected at a relatively high frequency and might be involved
      in the pathogenesis of this tumor among Jewish population in Israel.

PMID- 8747083
TI  - Transcription specific differences visualized by fluorescence in situ
      hybridization pattern on interphase nuclei of different cell types.
AB  - Application of a "formamide free" and thus "material preserving" in situ
      hybridization technique using the cDNA of the myf3 gene revealed the following
      results: Human rhabdomyosarcoma cells, characterized by a high expression of myf3
      show intensive hybridization signals in their interphase. RNase treatment prior
      to hybridization considerably reduces the size of this signals. In comparison,
      isolated nuclei of human lymphocytes in which no need for the expression of this
      gene exists, show barely hybridization signals. Correspondingly, RNase treatment
      had no effect on hybridization pattern at all. In conclusion an increased
      transcription efficiency of a cell type specific gene is accompanied by a higher
      hybridization accessibility in the corresponding cell nuclei.

PMID- 8747084
TI  - Autoantibodies to Auerbach's plexus in achalasia.
AB  - Achalasia is a motor disorder of the oesopagus characterized by decrease in
      ganglion cell density in Auerbach's plexus. The cause of the lesion is unknown.
      This is to repeat on the occurrence of autoimmune phenomena in patients with
      achalasia, in particular circulating antibodies against Auerbach's plexus and its
      possible meaning. IgG-antibodies against Auerbach's plexus were determined by
      standard indirect immunofluorescence. Antibodies to the cytoplasm of Auerbach's
      plexus were found in 37 of 58 patients with achalasia at variable stages of the
      disease (I-IV) with a disease duration ranging from 1 to 20 years but only in 4
      out of 54 healthy controls (specificity 93%, sensitivity 64%, p < 0.0001), and in
      none of 12 patients with Hirschsprung's disease as well as 12 patients with
      cancer of oesophagus and only in one of 11 patients with peptic oesophagitis as
      well as in one of 13 patients with myasthenia gravis. The present observations
      suggest that autoimmunity to Auerbach's plexus plays a role in the pathogenesis
      of achalasia, the mechanism of action is unknown.

PMID- 8747085
TI  - Phenotype of in vitro human otosclerotic cells and its modulation by TGF beta.
AB  - A study was carried out to obtain a more detailed picture of the phenotypes of
      human otosclerotic and normal bone cells and to analyse the response of both
      populations to treatment with TGF beta 1. Total collagen synthesis was found to
      be decreased, but fibronectin secretion increased in otosclerotic with respect to
      normal cells. Although overall glycosaminoglycan (GAG) synthesis was lower in
      otosclerotic cells, the sulphated GAG to hyaluronic acid (HA) ratio was higher,
      in particular there was greater expression of chondroitin (CS) and dermatan
      sulphates (DS). TGF beta 1 induced a more marked increase in collagen and
      fibronectin release and greater production of sulphated GAGs as DS and heparan
      sulphate (HS) in the otosclerotic cells. The fact that the phenotype of the
      otosclerotic cells differed from that of the normal cells and could be modified
      by TGF beta 1 treatment, suggests that TGF beta 1 is implicated in the
      pathogenesis of otosclerosis.

PMID- 8747086
TI  - Immunocytochemical study of binding and internalization of carrier-free Cu, Zn
      Superoxide dismutase by cultured rat hepatocytes.
AB  - Internalization of superoxide dismutase-gold complex by isolated liver cells has
      been shown to occur via receptor-mediated endocytosis. As colloidal gold may act
      as a carrier in this process, carrier-free human Cu, Zn superoxide dismutase was
      incubated with cultured rat hepatocytes. Light and electron microscopy
      immunocytochemistry revealed the binding and internalization of free native human
      Cu, Zn superoxide dismutase (hSOD) by cultured rat hepatocytes.
      Immunocytochemical demonstration of binding to the cell surface (hepatocytes were
      incubated with hSOD for 15 min. at 4 degrees C) and internalization (hepatocytes
      were incubated with hSOD for 15, 30 and 60 min. at 37 degrees C) of the carrier
      free superoxide dismutase was achieved by using a monoclonal antibody selectively
      reacting with the human protein. The results obtained indicate that carrier-free
      superoxide dismutase is bound and internalized by rat hepatocytes in primary
      cultures and that the enzyme can enter the cells via a receptor-mediated
      endocytosis pathway. We followed the binding and the internalization process of
      hSOD thus validating the use of the native enzyme in the therapy of free radical
      related diseases.

PMID- 8747087
TI  - Age-related changes of RNA synthesis in the lungs of aging mice by light and
      electron microscopic radioautography.
AB  - The changes of RNA synthesis and morphology in the lungs of aging mice from fetal
      day 16 to 22 months after birth were investigated by means of light and electron
      microscopic radioautography after 3H-uridine incorporation. Eleven groups of
      mice, each consisting of 3 animals from embryo day 16 to newborn, weanling, adult
      and senescent were used. Lung tissues were labelled in vitro with 3H-uridine and
      fixed, embedded, sectioned and radioautographed. The localization and number of
      silver grains were analyzed. The radioautograms revealed that all types of
      pulmonary tissue cells were labelled. The number of silver grains in respective
      cell types indicating the RNA synthesis changed with aging. The activity of RNA
      synthesis of type 1 epithelial cells increased gradually from the first day after
      birth, reached a peak at 1 week after birth, then decreased with aging. The RNA
      synthesis of type 2 epithelial, interstitial and endothelial cells increased
      gradually from fetal day 16, reached the peaks at 1 week after birth, then
      diminished with the developing of the lung due to aging.

PMID- 8747088
TI  - Changes in the neuronal plasma membrane during synaptogenesis.
AB  - During synaptogenesis the plasma membrane of neurons undergoes considerable
      changes and large portions of it develop to synaptic membranes. This
      transformation is brought about by biochemical and morphological changes. The aim
      of the present investigation was to study by morphological methods the in vivo
      changes of some basic components of the neuronal membranes during the early
      postnatal period, when active synaptogenesis occurs. The cerebral cortex of
      Wistar rats was used for preparation of either growth cones (up to postnatal day
      10) or synaptosomes (postnatal days 14-30). Our studies were focused on the
      changes occurring in integral membrane proteins and cholesterol domains, and in
      certain carbohydrate residues and anionic sites. In the first days after birth
      relatively few intramembranous particles are found in the plasma membranes of
      growth cones, few and small cholesterol domains, scarce lectin-binding and
      anionic sites. During the following days there is a clear tendency for increase
      of the number of all of the studied structures until the appearance of typical
      synaptic membranes. Throughout the studied developmental period the protein and
      the cholesterol molecules were found to occupy distinct membrane domains. The
      structure of the developing neuronal membrane, poor on proteins and cholesterol,
      and its maturation to the fully functional synaptic membrane is discussed.

PMID- 8747089
TI  - Effects of the tripeptide glycyl-L-histidyl-L-lysine copper complex on
      osteoblastic cell spreading, attachment and phenotype.
AB  - We have studied the effects of the complex Glycyl-L-Histidyl-L-Lysine:Cu
      (GHK:Cu), the GHK sequence present in the alpha 2 (I) chain of human collagen
      (Coll I), and bone matrix glycoproteins containing either RGD (fibronectin, FN),
      or RGD and GHK (Coll I), on the spreading, attachment and markers of the
      osteoblast phenotype in rat calvaria cells (RC), human trabecular osteoblastic
      cells (HT) and human marrow stromal cells (HM). Coll I (20 micrograms/ml) and FN
      (20 micrograms/ml) coating enhanced osteoblastic cell spreading, whereas free
      GHK:Cu and GHK coating (10(-10)-10(-8) M) had no effect. FN and Coll I, as well
      as GHK:Cu and GHK, increased the attachment of RC and HT cells. The attachment of
      both total number of cells and alkaline phosphatase (ALP)-positive osteoblastic
      cells was increased, showing no preferential effect on cells expressing this
      early marker of the osteoblast phenotype. In addition, immunocytochemical
      analysis showed that FN, Coll I and GHK:Cu coating increased both the total
      number of HM cells and the number of HM cells expressing Coll I or osteocalcin,
      indicating that GHK:Cu and RGD-containing proteins acted similarly on cells
      expressing different maturational stages. In contrast to its effect on cell
      attachment, GHK:Cu coating slightly inhibited the basal and 1,25(OH)2D-induced
      stimulation of ALP activity or osteocalcin production in rat and human
      osteoblastic cells. The finding that GHK promotes cell attachment and decreases
      the phenotype of normal rat and human osteoblastic cells suggests that
      osteoblasts may interact with free GHK or GHK-containing proteins in the bone
      matrix.

PMID- 8747090
TI  - Detection of human papillomavirus DNA in primary lung carcinoma by nested
      polymerase chain reaction.
AB  - Human papillomaviruses (HPV) have been implicated in the pathogenesis of human
      squamous cell carcinoma, especially of cervical carcinomas. In two previous
      studies concerning squamous cell carcinomas of the lung, DNA of HPV subtypes
      6/11/16/18 (and 31/33/35 for one study) was detected by in situ hybridization in
      7% to 30% of the cases. A series of 31 frozen biopsies of lung carcinomas were
      examined for the presence of HPVDNA by nested polymerase chain reaction (PCR).
      Type-specific primers (6/11, 16 and 18; Amplicis HPV(R)) located in the E6 or E7
      transforming region of HPV were used. HPV DNA was found in 2 of 18 cases (11%) of
      squamous cell carcinoma, in 1 of 4 cases of adenocarcinoma and in 2 of 7 cases of
      neuro-endocrine cancers. The two large cell undifferentiated carcinomas were HPV
      negative. There were three cases of HPV 6/11, one case of HPV 16, and one sample
      positive for HPV 6/11 and HPV 18. No any consistent morphologic change with HPV
      lesions could be observed whereas squamous metaplasia could be seen only in
      squamous cell carcinomas. The frequency of 11% among the squamous cell carcinomas
      is comparable to those previously reported in studies utilizing in situ
      hybridization. To our knowledge HPV DNA had never been detected previously in
      adenocarcinomas or neuro-endocrine tumors. This finding should be confirmed by
      the investigation of larger series, but suggests that HPV could play a role in
      carcinogenesis of different types of lung carcinoma, although at low frequency.

PMID- 8747091
TI  - Thymic nurse cell rescue of early CD4+CD8+ thymocytes from apoptosis.
AB  - We have now developed temperature sensitive lines of thymic nurse cells (TNCs),
      using the SV40 viral mutant tsA58, that maintain the ability to selectively
      internalize a subpopulation of alpha beta TCR+CD4+CD8+ thymocytes in vitro. One
      line, tsTNC-1, was shown to be able to rescue a subset of CD4+CD8+ thymocytes
      from programmed cell death at 32 degrees C, the temperature at which binding and
      internalization were detected. Rescue was significantly diminished at 38 degrees
      C, the temperature at which thymocyte binding was not observed. The rescued
      population of thymocytes showed a reduced level of apoptosis as measured by the
      DNA fragmentation assay. TNC rescue resulted in a shift of CD4+CD8+ thymocytes
      from immature TCRlow PNArhigh cells to the more mature TCRint PNArlow phenotype
      but no changes in cell surface levels of HSA nor CD69 were detected. The rescue
      activity of tsTNC-1 cells at 32 degrees C was significantly reduced with the
      addition of antibodies to either class I or class II MHC antigens. These results
      suggest that we have established TNC lines, using the SV40 viral mutant tsA58,
      that have the ability to rescue a subset of the TNC interactive thymocyte
      population from programmed cell death. The thymocyte population rescued by TNCs
      matures to a phenotype within the double positive stage of development that is
      indicative of positive selection.

PMID- 8747092
TI  - Characterization of human proteins that bind the repeated sequences in the
      squirrel monkey retrovirus enhancer.
AB  - We have recently identified two different human DNA-binding proteins, SMBP1 (35
      kDa) and SMBP2 (17 kDa), that specifically interact with the direct repeats of
      the enhancer sequence in the squirrel monkey retrovirus long terminal repeat.
      Herein, we report several biochemical properties of the human DNA-binding
      proteins. SMBP1 and 2 recognized an overlapped sequence of the 5' region of the
      repeat which contains a palindrome of CCAATGG. Both proteins required divalent
      cations such as Mg2+ and Ca2+ for their specific DNA binding at the optimum
      concentration of 1 mM. SMBP2 is a thermostable protein that binds tightly to the
      DNA sequence even by treatment at 80 degrees C for 15 min. The SMBP2-DNA complex
      was also stable in the presence of 300 mM NaCl. The resistance of SMBP2 to heat
      and salt treatment is a prominent character distinguishable from SMBP1 and other
      known transcriptional factors. SMBP1 and 2 can be easily separated by heparin
      agarose chromatography. These DNA-binding proteins were found to be present in
      nuclear extracts from several human cell lines including T cell, B cell, and
      epithelial cell.

PMID- 8747093
TI  - Internalization and biological effects of serum albumin in the breast cancer MCF
      7 and MDA-MB 231 cells.
AB  - We show that albumin is internalized by human breast cancer cells (MDA-MB 231 and
      MCF-7) in culture by using confocal laser scanning microscopy. Moreover, albumin
      has an effect on the level of radioactivity incorporated when the cells are
      incubated with radioactive estradiol, and it is necessary to observe the
      mitogenic effect of estradiol towards the MCF-7 cells. This finding opens some
      possibilities regarding the internalization mechanisms and fate (degradation,
      recycling) of albumin as well as the role played by this protein in the
      intracellular metabolism of estradiol and in the intra-extracellular traffic of
      estradiol and its metabolites.

PMID- 8747094
TI  - Effects of sera, basic fibroblast growth factor, heparin and cyclic AMP
      stimulation on proliferation of human vascular endothelial cells.
AB  - The aim of this study was to find culture conditions that optimize the
      proliferation of human endothelial cells (ECs). The effects of different sera,
      growth factors and other additives on ECs derived from the adult human great
      saphenous or the umbilical vein were studied. Human serum (HS) at 10 and 40% was
      significantly more effective than fetal calf serum at 10 and 30%, respectively.
      The addition of basic fibroblast growth factor (bFGF) increased proliferation
      alone and in combination with heparin. Heparin alone increased EC growth only in
      medium containing 40% HS. The addition of cholera toxin (CT) and a
      phosphodiesterase inhibitor (IBMX) to raise cAMP-levels, stimulated proliferation
      of both cell types but was more pronounced on the ECs from the saphenous vein.
      The cAMP-levels were elevated equally in both cell types. However, db-cAMP
      stimulated proliferation only of the ECs from the saphenous vein. An additive
      stimulatory effect was observed when bFGF and CT/IBMX were combined. For
      saphenous vein ECs, a medium containing HS (40%), bFGF, heparin, CT and IBMX was
      found optimal for proliferation. We conclude that these compounds may be used to
      increase EC growth and that, even a limited number of donor ECs may be sufficient
      starting material for in vitro studies on the human endothelium.

PMID- 8747095
TI  - Light microscopic radioautographic study on DNA synthesis of nerve cells in the
      cerebella of aging mice.
AB  - The morphological change and DNA synthesis of nerve cells in the cerebella of the
      aging mice were investigated by light microscopic radioautography using tritiated
      thymidine injection in vivo. During a period ranging from late fetal life to
      certain postnatal stages, 9 groups of mice were used. The labelled nuclei, which
      involved both the precursors of neurons and the glioblasts, were observed in the
      external granular layer of the cerebellum from embryonic day 19 to postnatal day
      14. It disappeared completely at 1 month. A peak of labeling index was observed
      at postnatal day 3. The glioblasts of the external granular layer migrated
      inward, some of them forming the Bergmann glia cells located between Purkinje
      cells, this at postnatal day 8, some penetrating in the internal granular layer.
      Labelled nuclei in the internal granular layer were also observed and a maximum
      of the labeling was seen at postnatal day 3, similarly to the external granular
      layer. With the development and the expansion of the cerebellum, the endothelial
      cells of the cerebellar vessels were progressively labelled, reaching a maximum
      during the first postnatal week. The obtained results provided consequently some
      data on the age-related changes of DNA synthesis of mouse cerebellum from later
      embryonic stages to postnatal stages. Different investigations will be necessary
      to explain these irregular sequences of labeling.

PMID- 8747096
TI  - Demonstrations of de-and remineralization mechanism as revealed in synthetic
      auditory ossicle (Apaceram) of rats by laser-Raman spectrometry.
AB  - In investigations of the process of bone destruction caused by chronic otitis
      media complicated with cholesteatoma, we proposed previously a hypothesis to
      explain its mechanism. In the present study, we substitute a synthetic auditory
      ossicle (Apaceram) for the bone to simplify the model system of experiments for
      our hypothesis. Its process was studied on a model simulation in vitro, in vivo
      and clinically at molecular level, using laser-Raman spectrometry. An increase of
      conductivity in both the saline solution and double-distilled water immersed
      Apaceram indicated demineralization depending on time lapse. The process of
      demineralization was revealed by the Raman spectral profiles as shown by
      narrowing a half-peak breadth (p < 0.01) of v1 signal (PO4(3-), 960 cm-1) and the
      disappearance of the shoulder at circa 950 cm-1 on the Apaceram surface implanted
      for 6 months. On the other hand, the process of remineralization was revealed in
      vivo by the spectral profiles: 1) a broader half-peak breadth (p < 0.01) of v1
      signal on the Apaceram surface implanted for 10 months than that implanted for 6
      months; 2) a weak reappearance of the shoulder at ca. 950 cm-1 on the Apaceram
      surface after 10 months; 3) four signals (v1 through v4) of PO4(3-) on the HOAP
      observed for inside the Apaceram shaft and 4) a weak v1 signal on both the
      granular fluorescent substance in the clinical case and the high density area of
      subcutaneous tissue after contact with the Apaceram in rats for 3 months. Judging
      from these investigations, it is proposed that the mechanism of bone destruction
      associated with cholesteatoma is a form of de- and remineralization.

PMID- 8747097
TI  - Mechanisms for controlling enzymatic reactions in foods.
AB  - Enzymes, as biocatalysts, are capable of specific manipulation of all the major
      biomolecules found in foods, and a wide variety of enzymes are therefore used as
      supplements for various food processing operations. There are, however, certain
      enzymes whose activities result in a rapid deterioration of food quality to be
      controlled in order to maintain quality and to extend product shelf-life. Various
      mechanisms and techniques for controlling the undesirable activities of such
      enzymes in foods have been developed ingeniously over the years by food
      scientists. These include traditional methods like low- and high-temperature
      treatment, chemical treatments, and control of water activity involving
      dehydration and salting. These techniques, however, have certain limitations,
      such as (1) changing the prime quality of certain foods, (2) health risks
      associated with certain chemical treatments, and (3) consumer preference for
      certain foods to be raw and "natural". Novel and potentially viable techniques
      such as pressurization, use of enzymes ("killer enzymes"), ionizing radiation,
      chemical modification of enzymes, and other naturally occurring protein
      inhibitors have therefore been developed to help alleviate some of these
      problems.

PMID- 8747098
TI  - Hyperactivity: is candy causal?
AB  - Adverse behavioral responses to ingestion of any kind of candy have been reported
      repeatedly in the lay press. Parents and teachers alike attribute excessive motor
      activity and other disruptive behaviors to candy consumption. However, anecdotal
      observations of this kind need to be tested scientifically before conclusions can
      be drawn, and criteria for interpreting diet behavior studies must be rigorous.
      Ingredients in nonchocolate candy (sugar, artificial food colors), components in
      chocolate candy (sugar, artificial food colors in coatings, caffeine), and
      chocolate itself have been investigated for any adverse effects on behavior.
      Feingold theorized that food additives (artificial colors and flavors) and
      natural salicylates caused hyperactivity in children and elimination of these
      components would result in dramatic improvement in behavior. Numerous double
      blind studies of the Feingold hypothesis have led to the rejection of the idea
      that this elimination diet has any benefit beyond the normal placebo effect.
      Although sugar is widely believed by the public to cause hyperactive behavior,
      this has not been scientifically substantiated. Twelve double-blind, placebo
      controlled studies of sugar challenges failed to provide any evidence that sugar
      ingestion leads to untoward behavior in children with Attention-Deficit
      Hyperactivity Disorder or in normal children. Likewise, none of the studies
      testing candy or chocolate found any negative effect of these foods on behavior.
      For children with behavioral problems, diet-oriented treatment does not appear to
      be appropriate. Rather, clinicians treating these children recommend a
      multidisciplinary approach. The goal of diet treatment is to ensure a balanced
      diet with adequate energy and nutrients for optimal growth.

PMID- 8747099
TI  - On modeling changes in food and biosolids at and around their glass transition
      temperature range.
AB  - Temperature-induced mechanical and other changes in biosolids are regulated by
      three types of kinetics, depending on whether the material is in the glassy
      state, undergoing a transition, or fully plasticized. The transition itself can
      take place over a considerable temperature range, which in many food and
      biological systems happens to be the most pertinent to their functionality and
      stability. At the transition onset, the plot of stiffness vs. temperature has a
      downward concavity. It is reversed only at an advanced stage of plasticization
      after much of the stiffness has already been lost. Consequently, the WLF,
      Arrhenius, or any other model that implies a continuous upward concavity cannot
      account for changes in the transition region, and it is unsafe to use them to
      predict properties through extrapolation. The mechanical changes in the
      transition region can be described by a model with the mathematical structure of
      Fermi's function. Its applicability has been demonstrated with published data on
      a variety of foods and biosolids. Because the plot of stiffness vs. moisture, or
      water activity, has the same general shape as that of the stiffness vs.
      temperature plot, it too can be described by a model with the same mathematical
      format. Because moisture lowers the transition center temperature in a manner
      that can be described by a simple algebraic expression, the combined effects of
      temperature and moisture can be incorporated into a single general model. The
      latter can be used to create three-dimensional displays of the stiffness
      temperature-moisture characteristic relationships of biosolids at and around
      their transition. At temperatures well above that of the transition, though,
      where a plot of log stiffness vs. temperature has a clear upper concavity, this
      model is no longer applicable, and the changes are better described by the WLF or
      an alternative model.

PMID- 8747100
TI  - Carrageenans and their use in meat products.
AB  - Carrageenans are sulfated linear polysaccharides of D-galactose and 3,6-anhydro-D
      galactose extracted from red seaweeds. They have been used by the food industry
      for their gelling, thickening, and stabilizing properties, and more recently by
      the meat industry for reduced fat products. Meat is a complex system of muscle
      tissue, connective tissue, fat, and water; during processing, numerous
      interactions occur among all these components. These interactions are responsible
      for the functional properties of the meat system. In meat products, carrageenans
      contribute to gel formation and water retention. Their addition is of special
      interest in low-fat meat products because fat reduction often leads to
      unacceptable, tough textures. When carrageenans are incorporated in these
      formulations, they improve the textural characteristics of the product by
      decreasing toughness and increasing juiciness. Although carrageenan interactions
      with milk proteins have been studied extensively, the mechanism by which
      carrageenans interact with meat proteins and the other meat components is not
      fully understood.

PMID- 8747101
TI  - Spoilage and shelf-life extension of fresh fish and shellfish.
AB  - Fresh fish and shellfish are highly perishable products due to their biological
      composition. Under normal refrigerated storage conditions, the shelf life of
      these products is limited by enzymatic and microbiological spoilage. However,
      with increasing consumer demands for fresh products with extended shelf life and
      increasing energy costs associated with freezing and frozen storage, the fish
      processing industry is actively seeking alternative methods of shelf life
      preservation and marketability of fresh, refrigerated fish and at the same time
      economizing on energy costs. Additional methods that could fulfill these
      objectives include chemical decontamination, low-dose irradiation, ultra-high
      pressure, and modified atmosphere packaging (MAP). This review focuses on the
      biochemical and microbiological composition of fresh fish/shellfish, the spoilage
      patterns in these products, factors influencing spoilage, and the combination
      treatments that can be used in conjunction with refrigeration to extend the shelf
      life and keeping quality of fresh fish/shellfish. The safety concerns of
      minimally processed/MAP fish, specifically with respect to the growth of
      Clostridium botulinum type E, is also addressed.

PMID- 8747102
TI  - The polymerase chain reaction: applications for the detection of foodborne
      pathogens.
AB  - Faster methods for the detection of foodborne microbial pathogens are needed. The
      polymerase chain reaction (PCR) can amplify specific segments of DNA and is used
      to detect and identify bacterial genes responsible for causing diseases in
      humans. The major features and requirements for the PCR are described along with
      a number of important variations. A considerable number of PCR-based assays have
      been developed, but they have been applied most often to clinical and
      environmental samples and more rarely for the detection of foodborne
      microorganisms. Much of the difficulty in implementing PCR for the analysis of
      food samples lies in the problems encountered during the preparation of template
      DNAs from food matrices; a variety of approaches and considerations are examined.
      PCR methods developed for the detection and identification of particular
      bacteria, viruses, and parasites found in foods are described and discussed, and
      the major features of these reactions are summarized.

PMID- 8747104
TI  - Ask the expert: what is the appropriate work-up for a child with hypercalciuria?

PMID- 8747103
TI  - Renal allograft survival according to primary diagnosis: a report of the North
      American Pediatric Renal Transplant Cooperative Study.
AB  - The data base of the North American Pediatric Renal Transplant Cooperative Study
      (NAPRTCS) was used to examine the effect of primary diagnosis on the outcome of
      renal transplantation in children. The relative risk of graft failure for eight
      diagnostic groups was determined, with patients with congenital and structural
      anomalies of the urinary tract serving as the reference group. Covariate analysis
      was used to control for the effects of age, race and transfusion history in
      recipients of living-related donor kidneys, and for age, donor age,
      antilymphocyte prophylaxis, prior transplantation, prior dialysis and cold
      ischemia time in recipients of cadaver kidneys. In recipients of living-related
      donor kidneys, the lowest graft failure rates were associated with the diagnoses
      of cystinosis, familial nephritis and hemolytic uremic syndrome (HUS), while the
      highest failure rates were observed in patients with a primary diagnosis of
      congenital nephrotic syndrome (CNS) or focal segmental glomerulosclerosis (FSGS).
      In cadaver allograft recipients, the lowest graft failure rates were associated
      with primary diagnoses of glomerulonephritis, congenital/structural disease and
      cystinosis, while patients with FSGS, HUS and CNS had the highest graft failure
      rates. This study suggests that patients with a primary diagnosis of cystinosis
      have superior outcomes, while the diagnoses of FSGS and CNS carry with them the
      highest risks of graft failure.

PMID- 8747105
TI  - The treatment of cystinosis with cysteamine and phosphocysteamine in the United
      Kingdom and Eire.
AB  - Fifty-nine patients with cystinosis were treated with cysteamine or
      phosphocysteamine in the United Kingdom up to May 1990. Treatment was started at
      a median age of 3.2 years (range 0.6-24.8 years) and continued for a median
      duration of 3.0 years (range 0.01-1.2 years). At the end of the study, 46 (78%)
      patients remained on treatment. One patient developed end-stage renal failure and
      6 died. Efficacy was assessed in the 44 pre-transplant patients. The United
      Kingdom pre-transplant patients had significantly lower plasma creatinine
      concentrations at 6 and 8 years than a historical group of patients who did not
      receive cysteamine (P < 0.0001 and P < 0.0003, respectively). There was no
      significant difference between pretreatment and final post-treatment height
      standard deviation scores, suggesting maintenance of growth rate. The leucocyte
      cystine concentration was less than the accepted upper limit of the treatment
      range (1 nmol 1/2 cystine/mg protein) in only 21% of determinations. There was no
      significant difference between the mean pre-treatment and final values of
      leucocyte cystine concentration. The mean final doses of cysteamine (33 mg/kg per
      day) and phosphocysteamine (37 mg/kg per day base equivalent) were less than the
      mean dose (51 mg/kg per day) used in a United States multicentre trial. We
      conclude that cysteamine treatment was beneficial, but further improvements might
      be achieved by an improvement in monitoring of therapy.

PMID- 8747106
TI  - Hepatocellular injury in Streptococcus pneumoniae-associated hemolytic uremic
      syndrome in children.
AB  - Streptococcus pneumoniae is an uncommon etiological organism in hemolytic uremic
      syndrome (HUS). Production of neuraminidase by S. pneumoniae results in exposure
      of red blood cell T-antigen, resulting in hemolysis, thrombocytopenia, and acute
      renal failure. Hepatic involvement in this form of HUS has not been described in
      the literature. We report in three children with S. pneumoniae-associated HUS the
      presence of severely elevated transaminases and conjugated hyperbilirubinemia.
      Increases in asparagine transaminase ranged from 11 to 46 times normal values and
      an increase in alanine transaminase ranged from 1.6 to 8 times normal. In all
      patients the rise in total bilirubin was 7-15 times normal. Biliary tree
      obstruction and viral causes for liver dysfunction were absent. Hepatocellular
      injury in S. pneumoniae-associated HUS likely results from mechanisms involved in
      sepsis and pneumonia-induced jaundice, combined with severely increased bilirubin
      production following massive hemolysis. The hepatic injury in all three patients
      resolved within 9, 5, and 10 days. Our experience suggests that an extensive
      evaluation including liver biopsy is not indicated.

PMID- 8747107
TI  - Cytokines in childhood hemolytic uremic syndrome and thrombotic thrombocytopenic
      purpura.
AB  - Serum and urine cytokines were analyzed in children with hemolytic uremic
      syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Interleukin-6 (IL
      6) was elevated in the serum of 33 of 35 children with HUS (94%) and in 2 of 2
      children with recurrent TTP. Serum IL-6 was higher in children with HUS who
      developed anuria, extrarenal manifestations during the acute phase of illness
      and/or chronic renal sequelae. Tumor necrosis factor-alpha (TNF-alpha) was
      detected in the serum of 7 patients with HUS (20%) and 1 patient with TTP. IL-6
      and TNF-alpha were elevated in the urine of 4 of 4 children with HUS and 2 of 2
      children with TTP. Urinary levels were higher than serum levels, suggesting local
      production of cytokines in the urinary tract. Sequential serum and urine samples
      showed that IL-6 levels varied with disease activity. IL-6 and TNF-alpha were not
      detected in the serum (n = 25) and urine (n = 15) of healthy children. We
      conclude that IL-6 in urine may be used to monitor disease activity in HUS and
      TTP.

PMID- 8747108
TI  - Escherichia coli verotoxin binding to human paediatric glomerular mesangial
      cells.
AB  - Haemolytic uraemic syndrome (HUS) remains the leading cause of acute renal
      failure in children. Although an Escherichia coli-produced verotoxin (VT) has
      been implicated in the pathogenesis of HUS, the precise mechanisms of disease are
      not well defined. We hypothesise that the pathogenesis of renal failure in HUS
      includes the binding of E. coli VT to the glomerular mesangial cell, with
      consequent effects on renal function. Using human paediatric mesangial cells, we
      studied the binding and biological effects of the purified verotoxin VT-1. We
      isolated, purified and characterised paediatric glomerular mesangial cells. The
      mesangial cells were characterised by their immunoreactivity with both smooth
      muscle actin and vimentin antibodies, and lack of immunoreactivity with
      cytokeratin or factor VIII antibodies. Using an fluorescein isothiocyanate
      conjugated VT (10(-7)-10(-8) M), we demonstrated specific binding to the
      mesangial cell membrane by immunofluorescence microscopy. We also demonstrated a
      dose-dependent inhibition of mesangial cell mitogenesis at concentrations from
      10(-9) to 10(-17) M. Our data demonstrate that VT-1 binds to paediatric human
      glomerular mesangial cells and this binding results in specific biological
      actions, including an inhibition of cell mitogenesis.

PMID- 8747109
TI  - Glomerular and tubular function in glycogen storage disease.
AB  - Urinary protein and calcium excretion were assessed in 77 patients with the
      hepatic glycogen storage diseases (GSD): 30 with GSD-I (median age 12.4 years,
      range 3.2-32.9 years), 25 with GSD-III (median age 10.5 years, range 4.2-31.3
      years) and 22 with GSD-IX (median age 11.8 years, range 1.2-35.4 years). Inulin
      (Cinulin) and para-aminohippuric acid (CPAH) clearances were also measured in 33
      of these patients. Those with GSD-I had significantly greater albumin (F = 15.07,
      P < 0.001), retinol-binding protein (RBP) (F = 14.66, P < 0.001), N-acetyl-beta-D
      glucosaminidase (NAG) (F = 9.41, P < 0.001) and calcium (F = 7.41, P = 0.001)
      excretion than those with GSD-III and GSD-IX. GSD-I patients (n = 18) also had
      significantly higher Cinulin (F = 5.57, P = 0.009), but CPAH did not differ (F =
      0.77, NS). Renal function was normal in GSD-III and GSD-IX patients. In GSD-I,
      Cinulin (r = -0.51, P = 0.03) and NAG excretion (r = -0.40, P = 0.03) were
      inversely correlated with age, whereas albumin excretion was positively
      correlated with age (r = +0.41, P = 0.03). RBP and calcium excretion were
      generally high throughout all age groups. Hyperfiltration in GSD-I is associated
      with renal tubular proteinuria that occurs before the onset of significant
      albuminuria. Deficiency of glucose-6-phosphatase within the proximal renal tubule
      may primarily cause tubular dysfunction, glomerular hyperfiltration being a
      secondary phenomenon.

PMID- 8747110
TI  - Microcephaly and early-onset nephrotic syndrome--confusion in Galloway-Mowat
      syndrome.
AB  - We report a 2-year-old girl with nephrotic syndrome, microcephaly, seizures and
      psychomotor retardation. Histological studies of a renal biopsy revealed focal
      glomerular sclerosis with mesangiolysis and capillary microaneurysms. Dysmorphic
      features were remarkable: abnormal-shaped skull, coarse hair, narrow forehead,
      large low-set ears, almond-shaped eyes, low nasal bridge, pinched nose, thin lips
      and micrognathia. Cases with this rare combination of microcephaly and early
      onset of nephrotic syndrome with various neurological abnormalities have been
      reported. However, clinical manifestations and histological findings showed a
      wide variation, and there is a lot of confusion in this syndrome. We therefore
      reviewed the previous reports and propose a new classification of this syndrome.

PMID- 8747111
TI  - Resolution of vesicoureteral reflux during medical management in children.
AB  - A retrospective study was performed to evaluate the results of medical management
      of primary vesicoureteral reflux (VUR) in infants and children. The charts of 105
      patients (74 boys, 31 girls) with 167 refluxing ureters were reviewed. The age at
      diagnosis ranged from 3 days to 9.2 years (mean 1.3 +/- 1.9 years). The mean
      duration of follow-up was 2.4 +/- 1.5 years. We found that the patient's sex did
      not influence the fate of VUR and its complications. Patients whose reflux
      improved while being managed medically were younger than those who did not
      improve, and the younger the patient the sooner the reflux resolved. Improvement
      and resolution of reflux were also related to grade, and the lower the initial
      grading the sooner the reflux resolved. Spontaneous resolution rates of reflux
      were 92.3%, 76.2%, 61.7%, and 32.0% for grades I, II, III, and IV, respectively.
      No ureters with grade V reflux resolved without complications. The most common
      complications in our series were renal scarring and secondary obstructive
      uropathy.

PMID- 8747112
TI  - Nonoliguric and oliguric acute renal failure in asphyxiated term neonates.
AB  - The purpose of this study was to determine the prevalence and types of acute
      renal failure in asphyxiated full-term neonates and to evaluate the accuracy of
      an asphyxia morbidity score in predicting acute renal failure. Neonates admitted
      to one institution from 1990 through 1993 with a gestational age > or = 36 weeks
      and 5-min Apgar score < or = 6, without congenital malformations or sepsis, were
      studied retrospectively for acute renal failure in the 1st week of life. Acute
      renal failure was defined as serum creatinine > 1.5 mg/dl (133 mumol/l) with
      normal maternal renal function. Nonoliguric renal failure was defined as renal
      failure with urine output > 1 ml/kg per hour after the 1st day. An asphyxia
      morbidity scoring system was used to distinguish severe from moderate asphyxia.
      The score ranged from 0 to 9 and was based upon fetal heart rate, Apgar score at
      5 min, and base deficit in the 1st h of life. The score for severe asphyxia was
      defined as 6-9 and for moderate asphyxia as 1-5. Sixty-six neonates fulfilled
      study criteria. Acute renal failure was present in 20 of 33 (61%) infants with
      severe asphyxia scores and 0 of 33 with moderate asphyxia scores (P < 0.0001).
      Acute renal failure was nonoliguric in 12 of 20 (60%), oliguric in 5 of 20 (25%)
      and anuric in 3 of 20 (15%). In conclusion 1) acute renal failure occurred in 61%
      of infants with severe asphyxia, 2) acute renal failure associated with severe
      asphyxia was predominantly nonoliguric and 3) an asphyxia morbidity score, which
      can be determined at 1 h of age, predicted acute renal failure in full-term
      infants with 100% sensitivity and 72% specificity.

PMID- 8747113
TI  - Pre-pubertal growth in the hyperprostaglandin E syndrome.
AB  - Pre-pubertal body growth was followed in eight children with the
      hyperprostaglandin E syndrome (neonatal Bartter syndrome) treated with
      indomethacin over a period of 5-12 years. When corrected for prematurity, the
      general growth pattern was normal, with the exception of a child with delayed
      therapy. From the first observation (usually at birth) to the start of
      indomethacin, the mean height standard deviation score (SDS) corrected for
      prematurity changed from -0.2 to -2.8. During the first 2 years of therapy rapid
      catch-up growth occurred, followed by a slow adaptation of the growth pattern to
      that of healthy children born at term. At last observation the mean corrected
      height SDS was -0.5 (range -1.9 to +0.9) and the mean target height -0.9 SDS
      (range -1.8 to +0.1). Weight, body mass index and bone maturation also reached
      the normal range. No correlation was found between height SDS per year and serum
      potassium levels or calcium excretion. We conclude that under indomethacin
      treatment long-term skeletal growth of children with the hyperprostaglandin E
      syndrome is similar to that of other preterm children.

PMID- 8747115
TI  - Pubertal growth in children with chronic renal failure on conservative treatment.
AB  - The pubertal growth spurt was followed for at least 3 years in 5 boys and 6 girls
      with chronic renal failure on conservative treatment. The peak height velocity
      averaged 8.6 cm/year (range 5.8-10.1 cm/year) in males and 8.2 cm/year (range 6.4
      11.5 cm/year) in females. In none was the pubertal growth spurt below the 3rd
      percentile for chronological age. At the end of the follow-up period, all
      patients but 2 had stature within the normal limits of parental target. The
      relative variation of height averaged - 0.013 standard deviation scores per year.
      On the whole, the pubertal growth spurt was normal in subjects with chronic renal
      failure on conservative treatment.

PMID- 8747114
TI  - Causes of increased renal medullary echogenicity in Turkish children.
AB  - The primary disorders of 50 children with increased renal medullary echogenicity
      on renal ultrasound were studied; 28 girls and 22 boys aged from 1 month to 16
      years were classified into four groups based on underlying disease and ultrasound
      findings. Group 1 was composed of 17 patients with distal renal tubular acidosis
      (34%); intense echoes throughout the pyramid were predominant. Group 2 consisted
      of 14 patients with vitamin D toxicity (28%) and an intense echogenic rim around
      the pyramids. Group 3 included 10 patients with different types of tubulopathies.
      A slight hyperechogenic rim around the sides and tip of the medullary pyramids
      was detected. Group 4 was made up of 9 patients with rare underlying conditions.
      Abdominal X-rays detected medullary calcinosis in only 12 (24%) of the total 50
      patients. Ultrasonography appears to be an important tool in the early diagnosis
      of increased renal medullary echogenicity and medullary nephrocalcinosis.

PMID- 8747116
TI  - Alphacalcidol oral pulses normalize uremic hyperparathyroidism prior to dialysis.
AB  - Alphacalcidol oral pulse therapy was given for secondary hyperparathyroidism to
      22 children (mean age of 5.6 years) with renal insufficiency. At the beginning of
      the study, the glomerular filtration rate was < 50% of normal, serum intact
      parathyroid hormone (PTH) was > 100 ng/l and the serum phosphate and calcium
      concentrations were within the normal range. Alphacalcidol (0.5-3.0 micrograms)
      was given orally thrice weekly in the evening and adjusted according to PTH,
      ionized calcium and phosphate concentrations. Serum PTH (mean +/- SEM) decreased
      significantly from a pre-treatment level of 393 +/- 81 ng/l to 122 +/- 34 ng/l
      after 12 months, and stabilized at this level. Mean vitamin D metabolite
      concentrations were within the normal range. 1,25-Dihydroxyvitamin D did not
      increase during therapy, while PTH decreased. The estimated creatinine clearance
      remained almost unchanged (20 +/- 3 and 21 +/- 6 ml/min per 1.73 m2). Growth
      remained low normal (height standard deviation score -1.8 +/- 0.3 initially and 
      1.7 +/- 0.4 12 months later) and bone mineral density did not decrease. We
      concluded that feedback regulation of PTH with oral alphacalcidol pulse therapy
      is effective in the treatment of hyperparathyroidism in children with renal
      failure prior to dialysis.

PMID- 8747117
TI  - Acute glaucoma and intracranial hypertension in a child on long-term peritoneal
      dialysis treated with growth hormone.
AB  - A 7-year-old boy with end-stage renal disease on long-term peritoneal dialysis is
      described. The child developed intracranial hypertension and acute glaucoma
      during therapy with recombinant human growth hormone (rhGH), 18 months after the
      onset of treatment. Symptoms developed within 1.5 days and required neurosurgical
      treatment to reduce the intracranial hypertension because of imminent impaction
      of the cerebellum and brain stem. After ventricular cerebrospinal fluid drainage
      and cessation of growth hormone, all symptoms of intracranial hypertension and
      increased intraocular pressure disappeared. To our knowledge this is the first
      report of intracranial hypertension or hydrocephalus and acute glaucoma during
      rhGH therapy. Continuous and long-term control of the ophthalmological and
      neurological status of patients treated with rhGh is indicated.

PMID- 8747119
TI  - Concealed administration of frusemide simulating Bartter syndrome in a 4.5-year
      old boy.
AB  - A 4.5-year-old boy was admitted to three different hospitals because of a
      tendency towards dehydration and polyuria, along with normal blood pressure,
      hypochloraemia, hypokalaemia, metabolic alkalosis and an impaired urinary
      concentrating ability. A renal biopsy failed to reveal juxtaglomerular
      hyperplasia. The clinical and laboratory findings failed to improve despite
      supplementation with potassium chloride and treatment with indomethacin. The
      urine was found to contain frusemide. The parents denied any drug administration
      to the boy. The child is now doing well more than 1 year after separation from
      his mother. Since ingestion of diuretic cannot be differentiated from true
      Bartter syndrome by blood and urinary electrolyte measurements alone, a diuretic
      screen is warranted in children with findings consistent with Bartter syndrome.

PMID- 8747118
TI  - C9 deficiency in a patient with poststreptococcal glomerulonephritis.
AB  - The case of a 10-year-old girl with congenital C9 deficiency and
      poststreptococcal glomerulonephritis (PSGN) is presented. Although her clinical
      symptoms mimicked those of Henoch-Schonlein purpura, histological examination of
      a renal biopsy specimen revealed the features commonly described in PSGN.

PMID- 8747120
TI  - Stimulation of growth hormone secretion in children with X-linked
      hypophosphatemia.
AB  - X-linked hypophosphatemia is characterized by low serum phosphorus, relative
      vitamin D deficiency and rickets. Despite adequate metabolic control with oral
      phosphate and vitamin D therapy, patients with X-linked hypophosphatemia have
      short stature. Whether growth hormone (GH) deficiency plays a role in short
      stature in patients with X-linked hypophosphatemia is not known. The purpose of
      this report was to investigate the response of GH to sequential paired
      pharmacological stimulation in patients with X-linked hypophosphatemia. Basal GH
      was 3.8 +/- 0.7 ng/ml, insulin-like growth factor-I (IGF-I) was 225 +/- 38 ng/ml
      and IGF binding protein-3 was 3.0 +/- 0.2 mg/l in 16 children studied with X
      linked hypophosphatemia. In response to L-dopa and arginine hydrochloride
      stimulation, serum GH rose to above 7 mg/ml in all patients. Thus, the short
      stature in patients with X-linked hypophosphatemia is not due to a GH/IGF-I
      secretory defect.

PMID- 8747121
TI  - Chylous ascites complicating neonatal peritoneal dialysis.
AB  - We report the development of chylous ascites in a neonate as an uncommon
      complication during continuous peritoneal dialysis. Cloudy dialysis fluid
      containing many white blood cells might confuse the diagnosis of chylous ascites
      with infective peritonitis and result in inappropriate use of antibiotics.
      Resolution may be critical, since chyle removal during dialysis may result in
      profound immunosuppression and malnutrition due to lymphocyte and fat losses.
      After 4 weeks on a modified diet, the chyle leak resolved. The patient returned
      to breast milk and continues nighttime continuous-cycle peritoneal dialysis
      without further chyle leak.

PMID- 8747122
TI  - Gastrointestinal function in chronic renal failure.
AB  - Feeding problems, anorexia and vomiting are common in infants and children with
      chronic renal failure (CRF), and play a major role in the growth failure often
      found in this condition. However, the gastroenterological and nutritional aspects
      of CRF in children have received little attention, hence therapeutic
      interventions are usually empirical and often ineffective. Gastritis, duodenitis
      and peptic ulcer are often found in adults with CRF on regular haemodialysis and
      following renal transplantation. Despite persistent hypergastrinaemia, gastric
      acid secretion is decreased rather than increased in most of these patients, and
      active peptic disease appears to be promoted by the removal of the acid output
      inhibition (neutralisation of gastric acid by ammonia) that follows active
      treatment. Helicobacter pylori, on the other hand, does not seem to play a
      significant role in the pathogenesis of peptic disease in CRF. Gastro-oesophageal
      reflux has been found in about 70% of infants and children with CRF suffering
      from vomiting and feeding problems, and thus appears to be a major problem in
      these patients. In a number of symptomatic patients with CRF, gastric
      dysrhythmias and delayed gastric emptying have also been found; hence there
      appears to be a complex disorder of gastrointestinal motility in CRF. Serum
      levels of several polypeptide hormones involved in the modulation of
      gastrointestinal motility [e.g. gastrin, cholecystokinin (CCK), neurotensin] and
      the regulation of hunger and satiety (e.g. glucagon, CCK) are significantly
      raised as a consequence of renal insufficiency, and can be reverted to normal by
      renal transplantation. Furthermore, several other humoral abnormalities (e.g.
      hypercalcaemia, hypokalaemia, acidosis, etc.) are not uncommon in CRF. By
      directly affecting the smooth muscle of the gut or stimulating particular areas
      within the central nervous system, all these humoral alterations may well play a
      major role in the gastrointestinal dysmotility, anorexia, nausea and vomiting in
      patients with CRF. Specific pharmacological and nutritional interventions should
      thus be considered for the treatment of vomiting and feeding problems in CRF.

PMID- 8747123
TI  - High-resolution light microscopy for interpretation of renal biopsies.
AB  - Routine transmission electron microscopy is recommended for all renal biopsies.
      However, most of the diagnostic lesions in renal pathology are 0.2 micron or
      larger, and are therefore visible by light microscopy. These lesions are
      difficult to evaluate in paraffin sections due to problems inherent in the method
      itself. Full utilization of the resolving power of the light microscope or high
      resolution light microscopy is possible with resin (plastic) histotechnology. The
      replacement of conventional histotechnology by epoxy histotechnology allows the
      visualization of most subcellular structures needed for accurate diagnosis in
      renal pathology. Electron microscopy remains a very helpful tool for selected
      morphological problems.

PMID- 8747125
TI  - The dark side of nitric oxide: mediator of cell injury.

PMID- 8747124
TI  - The prune-belly syndrome: current insights.
AB  - The prune-belly syndrome comprises a constellation of well-established physical
      findings, yet the cause and management remain controversial. This review focuses
      on the current understanding of its pathogenesis and characterizes the fetal and
      neonatal diagnosis and management. Other associated anomalies are discussed to
      understand better the factors affecting treatment and prognosis as these patients
      grow into childhood and beyond.

PMID- 8747126
TI  - Clinical quiz. Differential diagnosis of a patient with hypertension.

PMID- 8747127
TI  - Clinical quiz. Differential diagnosis of a patient with Wegener's granulomatosis.

PMID- 8747128
TI  - Megacystis-microcolon-intestinal-hypoperistalsis syndrome.

PMID- 8747129
TI  - Microangiopathic hemolytic anemia, thrombocytopenia, and renal injury during
      continuous venovenous hemodialysis in a neonate.

PMID- 8747130
TI  - Interrupted response to indomethacin treatment.

PMID- 8747131
TI  - Vitamin D metabolites in childhood nephrotic syndrome.

PMID- 8747132
TI  - Amyloidosis secondary to inflammatory pseudotumor: a rare association.

PMID- 8747133
TI  - Inefficacy of pefloxacin in steroid-responsive nephrotic syndrome.

PMID- 8747134
TI  - Acetylcholine as a regulator of neurite outgrowth and motility in cultured
      embryonic mouse spinal cord.
AB  - Time-lapse photography was used to examine the effects of acetylcholine on the
      outgrowth and motility of neurites in cultures of mouse spinal cord. Addition of
      acetylcholine to the culture medium at concentrations of 100, 10 and 1 microM,
      caused inhibition of neurite outgrowth. Outgrowth rates were significantly
      different from those of controls at all concentrations tested. The motility of
      the growth cones was significantly reduced by treatment with 100 and 10 microM
      acetylcholine. Blockade of the muscarinic receptor by atropine did not
      significantly alter the effects of acetylcholine on outgrowth or motility.
      However when the nicotinic antagonist mecamylamine was added at the same time as
      acetylcholine the inhibitory effects of the acetylcholine were blocked and no
      changes in the rate of neurite outgrowth or in growth cone motility were
      detected. These results suggest that acetylcholine may have a role in the
      regulation of process outgrowth within the spinal cord with these effects
      mediated through the nicotinic receptor.

PMID- 8747135
TI  - Cobalt-permeable non-NMDA receptors in developing chick brainstem auditory
      nuclei.
AB  - Kainate, an agonist at non-NMDA glutamate receptors, evoked strong concentration
      dependent cobalt accumulation in the chick brain stem auditory nuclei angularis,
      laminaris (NL) and magnocellularis (NM). This effect could be blocked completely
      by the AMPA/kainate receptor antagonist CNQX and the AMPA antagonist GYKI 53655
      but not by antagonists of NMDA receptors or voltage-sensitive calcium channels.
      Kainate (30 microM) evoked cobalt uptake from embryonic day (E)9 through E21,
      with a peak intensity at E15. Before E13, uptake occurred mainly in NL but
      declined markedly in NM after E15 and ceased in NL by E21. We conclude that
      calcium-permeable non-NMDA receptors are transiently expressed at the time when
      mature neuronal number, form and synaptic connectivity are established.

PMID- 8747136
TI  - Neurotrophin receptor expression during development of the chick spinal sensory
      ganglion.
AB  - The expression of mRNA for the trk neurotrophin receptors was studied in
      developing chicken dorsal root ganglion neurones using in situ hybridization
      histochemistry. trkC mRNA is expressed first, followed by trkB mRNA and finally
      trkA mRNA. The expression of each receptor begins very early during neurogenesis,
      and although initially quite widespread throughout the ganglion, the proportion
      of neurones expressing each receptor reduces as development proceeds. Expression
      patterns for each receptor become specifically restricted within the ganglion
      during this time, but during subsequent development the neurones migrate to their
      final site within the ganglion. From an assessment of the ganglion's ability to
      respond to neurotrophins in vitro, and from the results of earlier studies, both
      on the expression of receptors and gene targeting experiments, it is apparent
      that DRG neurones are dependent on these factors at very early stages of
      development and not, as previously thought, only after target innervation.

PMID- 8747137
TI  - IL-1 beta and TNF alpha, but not IL-6, induce alpha 1-antichymotrypsin expression
      in the human astrocytoma cell line U373 MG.
AB  - Cytokines such as interleukin-1 (IL-1) and interleukin-6 (IL-6) have previously
      been shown to participate in neurodegenerative processes including Alzheimer's
      disease. However, the molecular consequences of increased cytokine expression in
      the brain remain largely unknown. We have studied the effects of IL-1, IL-6 and
      TNF alpha on the expression of the acute-phase protein alpha 1-antichymotrypsin
      (ACT) in human astrocytoma cell lines. Both IL-1 and TNF alpha, but not IL-6,
      were able to induce ACT gene transcription and protein synthesis. The synthetic
      glucocorticoid dexamethasone enhanced cytokine-induced ACT mRNA expression and
      protein synthesis. We conclude that IL-1-induced expression of ACT may be part of
      the inflammatory response in the brain and may be involved in the pathology of
      Alzheimer's disease.

PMID- 8747138
TI  - Network analysis of PET-mapped visual pathways in Alzheimer type dementia.
AB  - Using path analysis to determine the systems-level neural networks mediating
      specific tasks from regional cerebral blood flow (rCBF) data obtained by positron
      emission tomography (PET), we recently found in young subjects strong functional
      linkages during a face matching task along a right hemisphere ventral network
      including occipital, temporal, and frontal regions. In this study, PET data
      obtained during a face matching task from mildly affected patients with dementia
      of the Alzheimer type (DAT) and healthy matched controls showed that (1) the
      neural model obtained in young subjects provides a good fit to data from old
      subjects; (2) although the DAT patients could perform this task with the same
      accuracy as controls, they did not use the same functional network.

PMID- 8747139
TI  - Cerebellar afferences from the mesencephalic trigeminal nucleus in the rat.
AB  - The aim of the present study was to test for and characterize the organization of
      a direct projection from neurones of the trigeminal mesencephalic nucleus (Vme)
      to the cerebellum. WGA-HRP was used as a retrograde tracer following injections
      in the cerebellar cortex. The extent of each injection site within the sagittal
      zones was determined according to corticonuclear and olivocortical connections.
      Retrogradely labelled neurons were observed in the caudal part of the ipsilateral
      Vme only following vermal injection. The Vme projections reached exclusively the
      ipsilateral sagittal zone X in the anterior lobe, lobule VI and lobule IX. This
      identification was confirmed by anterograde labelling of mossy fibre terminals
      following a biocytin injection restricted to the Vme.

PMID- 8747140
TI  - LTP in the barrel cortex of adult rats.
AB  - Intrinsic circuitry in the barrel cortex has been shown to be readily modifiable
      in response to changes in the patterns of sensory input, even in adult animals.
      It is believed that sensory experience modifies synaptic circuits by imposing
      specific patterns of repetitive presynaptic and postsynaptic coactivity, i.e. by
      LTP-like processes. However, the ability of intrinsic cynapses in the adult
      barrel cortex to express LTP has not been demonstrated. In slices from barrel
      cortex of adult rats, we show that input-specific LTP can be induced in the
      supragranular layers by tetanic stimulation of intracortical vertical and
      horizontal inputs.

PMID- 8747141
TI  - Effects of local anaesthesia on formalin-induced Fos expression in the rat dorsal
      horn.
AB  - A subcutaneous injection of formalin into foot pad of the rat produces a bimodal
      nociceptive response including an early intense response in the first 5 min and a
      later moderate response that is exhibited from 20 to 60 min after injection. In
      this study, we investigated the effects of blocking the early phase and late
      phase input, respectively, on Fos-like immunoreactivity (Fos-LI) expression in
      dorsal horn neurones. Rats of the early phase block (EB) group were injected with
      5% formalin (0.05 ml) into the footpad 5 min after a s.c. injection of 4%
      lidocaine (0.15 ml) into the angle. The rats of the late phase block (LB) group
      were injected with 5% formalin into the footpad 10 min before the s.c. injection
      of 3% prilocaine (0.20 ml) containing felypressin into the ankle. The rats of the
      control group were given the formalin injection alone. Fos-LI was detected in the
      dorsal horn 2 h after the formalin injection. The numbers of Fos-LI neurones in
      the dorsal horn of both EB and LB group were markedly decreased compared with the
      control group, being 31.3% (laminae I-III of EB), 37.1% (laminae I-III of LB),
      13.9% (laminae IV-VI of EB) and 16.2% (laminae IV-VI of LB) of the control
      values. No significant difference was observed between EB and LB group. These
      findings suggested that the early and late phase contribute in concert to the
      induction of genetic changes in dorsal horn neurones after formalin injection.

PMID- 8747142
TI  - Spinal expansion of saphenous afferents after sciatic nerve constriction in rats.
AB  - In rats with chronic constriction of one sciatic nerve, neurone pair responses to
      saphenous electrical stimulation were simultaneously recorded in sciatic (L5-6)
      and in saphenous (L2) spinal areas. In 16 rats with thermal hyperalgesia, 43
      pairs of neurons were recorded, 4 and 14 days after constriction, on both sides
      of the spinal cord. On the side ipsilateral to nerve constriction, stimulation of
      the saphenous evoked excitatory responses in 90% of neurones recorded in the L5
      L6 sciatic area, regardless of the post-constriction time. No responses were
      evoked by saphenous stimulation of the L5-L6 contralateral spinal cord neurones.
      The possibility that pre-existing connections are unmasked after nerve injury and
      impinge on sensitized neurones, contributing to abnormal pain sensations such as,
      for instance, extraterritorial pain, is discussed.

PMID- 8747143
TI  - Where the brain appreciates the moral of a story.
AB  - To identify the distributed brain regions used for appreciating the grammatical,
      semantic and thematic aspects of a story, regional cerebral blood flow was
      measured with positron emission tomography in nine normal volunteers during the
      reading of Aesop's fables. In four conditions, subjects had to monitor the fables
      for font changes, grammatical errors, a semantic feature associated with a fable
      character, and the moral of the fable. Both right and left prefrontal cortices
      were consistently, but selectively, activated across the grammatical, semantic,
      and moral conditions. In particular, appreciating the moral of a story required
      activating a distributed set of brain regions in the right hemisphere which
      included the temporal and prefrontal cortices. These findings emphasize that
      story processing engages a widely distributed network of brain regions, a subset
      of which become preferentially active during the processing of a specific aspect
      of the text.

PMID- 8747144
TI  - Retained cocaine conditioned place preference in D1 receptor deficient mice.
AB  - The role of the D1 dopamine receptor subtype in mediating cocaine effects was
      examined in mice in which the D1 receptor gene had been ablated by homologous
      recombination. Cocaine reward was assessed by conditioned place preference
      experiments using mice which had either one allele (+/-) or both alleles (-/-) of
      the D1 dopamine receptor gene disrupted and in their wild type (+/+) littermates.
      Cocaine conditioning resulted in similar increases in preference for drug-paired
      environments in mice of each of the three genotypes. Cocaine did not alter
      locomotor activity levels in homozygous, D1 knockout mice -/-, whereas increased
      activity was noted in both +/+ and +/- animals. These results are consistent with
      the idea that the D1 receptor is involved in the locomotor stimulant effects of
      cocaine, but has little role in a major test of the rewarding and reinforcing
      effects of the drug.

PMID- 8747145
TI  - From objective to subjective: pitch representation in the human auditory cortex.
AB  - Magnetic brain responses to infrequent changes in the pitch of complex sounds
      were recorded. The composition of the test sounds required that pitch-deviant
      stimuli elicited the mismatch response only if perceived pitch was represented in
      auditory sensory memory. Results revealed that subjective features, such as
      pitch, are formed from objective stimulus parameters (i.e. the spectral contents
      of a sound) before storing acoustic information in memory. The origin of the
      magnetic response to pitch change showed that pitch deviation was detected in the
      auditory cortex. Pitch memory might also be located in the auditory cortex, as
      previous evidence suggests that storage for an auditory feature lies in the
      vicinity of the neuronal elements activated by deviations in that feature.

PMID- 8747146
TI  - Continuous infusion of neuropeptide Y in the SCN decreases food intake in rats.
AB  - We investigated the effect of chronic infusion of neuropeptide Y (NPY) aimed at
      the hypothalamic suprachiasmatic nucleus (SCN) or the lateral cerebral ventricle
      (LCV) on food intake. The experiments were performed in adult male Wistar rats
      infused for 7 days with saline or NPY (10 and 100 pmol microliters-1 h-1) into
      the SCN (n = 18) or LCV (n = 17). Infusion of the lower dose of NPY in the SCN
      significantly decreased food intake, whereas infusion of the higher dose did not.
      There was no change in food intake specific to saline or either dose of NPY with
      infusion in the LCV. It is concluded that chronic infusion of NPY into the SCN at
      a dose of 10 pmol h-1 inhibits food intake in rats.

PMID- 8747147
TI  - Changing of an isolated neurone ultrastructure during a prolonged impact of
      mediator.
AB  - We investigated the influence of prolonged excitation or combined
      excitation/inhibition on the ultrastructural changes in an isolated stretch
      receptor neurone from crayfish abdomen. Excitatory impulse activity was achieved
      by mechanical stimulation of a neurone for 10 or 120 min and inhibition of the
      activity was obtained by perfusion with gamma-aminobutyric acid (GABA, 2.5 x 10(
      5) M) for the same periods. Changes in the ultrastructural components were
      observed following both excitatory and inhibitory stimulation for 120 min.
      Neuronal adaptation to excitatory or inhibitory stimuli after 120 min resulted in
      the appearance of an increased number of the giant mitochondria. Thus, the number
      of giant mitochondria may serve as an ultrastructural index of the degree of
      neuronal adaptation to external stimulation.

PMID- 8747148
TI  - Regulation of intracellular free calcium levels by the cellular prion protein.
AB  - A rat brain synaptosomal model was used to investigate the possible role of the
      cellular prion protein (PrP) in the regulation of intracellular free calcium
      levels ([Ca2+i). Treatment of synaptosomes with bacterially derived recombinant
      human PrP in the range 20-100 micrograms ml-1 resulted in dose-dependent
      elevations of [Ca2+]i. These increases were dependent on extracellular calcium
      and were inhibited by gadolinium chloride, a potent blocker of voltage-sensitive
      calcium channels. Conversely, when calcium channels were activated by
      synaptosomal depolarization, treatment with monoclonal antibody to PrP in the
      range 200-320 ng IgG ml-1 resulted in a dose-dependent reduction of [Ca2+i, which
      was blocked by competition with PrP preparations. These results indicate that PrP
      is associated with regulation of intracellular free calcium levels through an
      interaction with voltage-sensitive calcium channels.

PMID- 8747149
TI  - Capsaicin blocks Ca2+ channels in isolated rat trigeminal and hippocampal
      neurones.
AB  - Effects of capsaicin, an essential ingredient of hot peppers, on high voltage
      activated (HVA) calcium channels were investigated in voltage-clamped and
      internally perfused acutely dissociated rat trigeminal and hippocampal neurones.
      In micromolar concentrations capsaicin inhibited the whole HVA Ca2+ current
      without affecting resting membrane conductance in both types of neurones. IC50
      values of 14.5 microM and 21.2 microM (n = 5) were obtained in sensory and
      hippocampal neurones, respectively. Capsaicin-induced inhibition became
      irreversible after prolonged incubation (30 s) with the drug. It is concluded
      that capsaicin is a nonspecific blocker of HVA Ca2+ channels in different types
      of nerve cells.

PMID- 8747150
TI  - Visually-triggered oscillations in the cat lateral posterior-pulvinar complex.
AB  - The so-called 40 Hz oscillations are found at almost all stages of visual
      processing are thought to play a critical role in perception. The goal of this
      investigation was to look at the presence of stimulus-specific oscillations in
      the lateral posterior-pulvinar complex of the thalampus (LP-P) for which the
      oscillations were still not described. Rhythmic patterns in multiunit LP-P
      activity of anaesthetized cats were revealed in 14% of recording sites. With the
      exception of one pool of LP-P cells that exhibited stimulus-dependent rhythmic
      activity approximately 130 Hz, 90% of autocorrelograms were modulated between 18
      and 74 Hz with dominant frequencies of 20-33 Hz. Since the LP-P sends efferents
      to the visual cortex it seems possible that oscillations from the LP-P can
      propagate to cortical neurones, especially to complex cells, for which similar
      dominant frequencies were noted by previous investigators.

PMID- 8747151
TI  - Stimulus dependent intercolumnar synchronization of single unit responses in cat
      area 17.
AB  - Recent concepts of cortical information processing suggest that visual stimuli
      are represented by ensembles of synchronously firing neurones. This hypothesis
      predicts that individual cells in separate columns of the visual cortex should
      synchronize their discharges in response to a single coherent stimulus and fire
      asynchronously when each neurone responds to a different stimulus. To test this
      prediction, we recorded simultaneously with two stereotrodes from single units
      with non-overlapping, colinearly arranged receptive fields in area 17 of the
      anaesthetized cat. In support of the hypothesis, cell pairs activated by the same
      long bar stimulus discharged in synchrony, and fired with no or diminished
      temporal correlation when each neurone was activated by an independent light bar.

PMID- 8747152
TI  - Immunodetection of serotonin transporter from mouse brain.
AB  - A DNA fragment encoding amino acid sequences from the amino terminal region of
      the mouse serotonin transporter was isolated and sequenced. This transporter is
      widely distributed throughout the mouse brain, as deduced by heminested reverse
      transcription-polymerase chain reaction (RT-PCR) assays. To identify the
      serotonin transporter protein, we have developed specific antibodies against a
      fusion protein containing its amino terminal region, a domain which shows a low
      degree of homology between the different neurotransmitter transporters. Western
      blot analysis of mouse brain membranes detected the serotonin transporter as a 71
      kDa polypeptide.

PMID- 8747153
TI  - Neuronal high-affinity glutamate transport in the rat central nervous system.
AB  - EAAC1 is a neuronal and epithelial high affinity glutamate transporter previously
      cloned from rabbit intestine. Here we report the isolation of EAAC 1 from rat
      brain* and its expression in the central nervous system based on in situ
      hybridization. Strong signals were detected in brain, spinal cord and retina.
      Expression of EAAC1 was particularly strong in pyramidal cells of the cerebral
      cortex, pyramidal cells of the hippocampus, mitral cells of the olfactory bulb,
      various thalamic nuclei and cells of certain retinal layers. EAAC1 was also
      expressed in non-glutamatergic neurons such as GABAergic cerebellar Purkinje
      cells and alpha-motor neurons of the spinal cord. We propose that EAAC1 is not
      only involved in the sequestration of glutamate at glutamatergic synapses and in
      protecting neurons from glutamate excitotoxicity, but also in the cellular
      metabolism involving glutamate.

PMID- 8747154
TI  - Intelligible speech encoded in the human brain stem frequency-following response.
AB  - The human brain stem frequency-following response (FFR) registers phase-locked
      neural activity to cyclical auditory stimuli. We show that the FFR can be
      elicited by word stimuli, and when speech-evoked FFTs are reproduced as auditory
      stimuli they are heard as intelligible speech. Stimuli were 10 high- and 10 low
      probability words drawn from normative verbal responses of university students.
      Horizontal and vertical dipole FFRs based on 1000 repetitions of each word were
      recorded from two different participants. Speech-evoked FFRs were evaluated by 80
      listeners. The results showed significant effects of FFR participant, word
      probability, and whether or not words were presented with category cues.
      Depending on such subject and experimental variables, FFRs were correctly
      perceived from 5% to 92% of the time.

PMID- 8747155
TI  - Complementary distribution of the phosphoproteins DARPP-32 and I-1 in the
      cerebellar system.
AB  - DARPP-32 (a dopamine and adenosine 3':5'-monophosphate (cAMP) regulated
      phosphoprotein of M(r) 32 kDa) and I-1 (phosphatase inhibitor-1) are related
      phosphoproteins that have distinct regional distributions in some specific
      neuronal structures. To determine whether they are also expressed in different
      types of neurons we investigated their distribution in the cerebellum, whose
      cellular structure is well characterized. In the cerebellar cortex, antibodies to
      DARPP-32 labeled Purkinje cells and antibodies to I-1 labeled granule cells. The
      two phosphoproteins were also in synaptic apposition in the deep cerebellar
      nuclei as well as in nuclei that project to the cerebellum via the climbing fiber
      and mossy fiber systems. This pattern was consistent in different mammalian
      species, including the mouse, marmoset, rhesus monkey and the mutant mouse
      reeler. We suggest that DARPP-32 and I-1 have distinct roles in regulating
      neuronal excitability in the cerebellum and may play different parts in the
      phenomenon of long-term depression (LTD).

PMID- 8747156
TI  - Attenuation of gastrin-induced gastric acid secretion by antisense
      oligonucleotide to the CCKB/gastrin receptor.
AB  - The effects of treatment with CCK receptor antagonists or administration of an
      antisense oligonucleotide to the gastrin receptor, on gastrin-I and
      cholecystokinin-8-induced acid secretion in mouse stomach were evaluated.
      Administration of gastrin-I (1 microM) or cholecystokinin-8 (30 nM) stimulated
      acid output at the rates of 2.6 +/- 0.27 and 1.0 +/- 0.21 microEq h-1,
      respectively. Gastrin-I-induced acid output was significantly blocked by
      pretreatment of stomachs with 3R[+]-N-[2,3-dihydro-1-methyl-2-oxo-5- phenyl-1H
      1,4-benzodiazepin-3-yl]-N[3-methylphenyl[urea (L-365,260; 1 microM), but not by
      devazepide (L-364,718; 1 microM). Cholecystokinin-8-induced acid output, on the
      other hand, was sensitive to both L-365,260 (100 nM) and L-364,718 (100 nM).
      Administration of antisense, but not mismatch, oligonucleotide significantly
      reduced gastrin-induced acid output, while antisense oligonucleotide treatment
      had no effect on cholecystokinin-8-induced acid output. These results of
      antagonist and antisense oligonucleotide studies suggest that gastrin-I and
      cholecystokinin-8 may involve different receptor subtypes in stimulating gastric
      acid secretion in mice, and that antisense oligonucleotide administration may
      serve an useful tool in characterizing CCK/gastrin receptor subtypes.

PMID- 8747157
TI  - Bufotenine reconsidered as a diagnostic indicator of psychiatric disorders.
AB  - We have analyzed products of the serotonin-degradative pathway, in which both N
      methylserotonin and bufotenine are formed in urine specimens of products with
      psychiatric disorders by three-dimensional HPLC with electrochemical detection.
      Bufotenine was detected in urine from all autistic patients with mental
      retardation and epilepsy (n = 18) and many autistic patients (32/47) with mental
      retardation. Bufotenine was detected in the urine of 15 of 18 patients with
      depression. Thirteen of 15 schizophrenic patients were also positive for
      bufotenine. N-methylserotonin was also detected in some cases of each disorder.
      Only two of 200 urine specimens from healthy controls were positive for
      bufotenine. Thus, the presence and levels of bufotenine might be useful and
      important markers of some psychiatric disorders.

PMID- 8747158
TI  - Phosphorylation of tau protein is not affected in mice lacking apolipoprotein E.
AB  - An interaction between the apolipoprotein E (apoE) type 3 and the microtubule
      associated protein tau has been demonstrated in vitro and suggested to modulate
      tau phosphorylation and/or formation of paired helical filaments. To evaluate in
      vivo the potential interaction between tau and apoE, we have investigated the
      expression and phosphorylation status of tau in the brain of apoE-deficient mice,
      using a panel of antibodies reacting with tau in a phosphorylation-dependent
      manner. The pattern and intensity of immunohistochemical labelling and the
      pattern of tau immunoreactivity on Western blots were similar in control and apoE
      deficient mice. These results suggest that a lack of expression of apoE does not
      interfere with the expression, distribution and phosphorylation status of tau
      proteins.

PMID- 8747159
TI  - Nuclear [3H]naloxone binding in rat hypothalamus.
AB  - High affinity (Kd approximately 1 nM) and low capacity [3H]naloxone binding sites
      were detected in the nuclear fraction of rat hypothalamus. The profile of this
      binding changed with age. In immature rats from 11 days of age until vaginal
      opening (approximately 33 day) the Scatchard plots of saturation data were linear
      and the Hill coefficient was 1, while just after vaginal opening (< 6 h)
      Scatchard analysis of [3H]naloxone binding gave a curvilinear component, with the
      Hill coefficient approximately 2, followed by an increase in binding sites and a
      decrease in Kd. In adults, after ovariectomy, the pattern of [3H]naloxone binding
      was similar to that observed in immature rats before vaginal opening. Following
      oestradiol treatment, binding sites with linear Scatchard plots disappeared and
      returned at least 24 h after hormone administration.

PMID- 8747160
TI  - Open field behaviour in rats: role of metabotropic glutamate receptors.
AB  - Previous studies have shown that spatial memory retention is affected by the
      metabotropic glutamate receptor (mGluR) influencing agents (R,S)-alpha-methyl-4
      carboxyphenylglycine (MCPG) and trans-azetidine-2,4-dicarboxylic acid (tADA). In
      the present investigation we examined whether the mGluR antagonist MCPG (20 mM
      and 200 mM/5 microliters, respectively) and the agonist tADA (20 mM/5
      microliters) have other behavioural effects using the open field test on two
      successive days. Only minor effects of MCPG (decrease of crossings during the 1st
      min on day 1) and tADA (increase of rearings on both days) were found. These
      results suggest that memory influencing doses of MCPG and tADA have no or only
      little behavioural effects in the open field situation.

PMID- 8747161
TI  - Random catecholaminergic differentiation of mesencephalic neural precursors.
AB  - We investigated how several factors influence the catecholaminergic phenotype
      establishment from embryonic mesencephalic neural precursors in culture. Using a
      semiquantitative RT-PCR procedure we found no significant effect of several
      growth factors or conditioned media on tyrosine hydroxylase (TH) mRNA levels.
      Nevertheless, neural precursor cells expanded by epidermal growth factor (EGF)
      and basic fibroblast growth factor (bFGF) showed the ability to express TH mRNA.
      Subcultures of EGF expanded neural precursor cells expressed TH mRNA, but not all
      individual secondary colonies obtained had this characteristic. Preferential
      dopaminergic differentiation was observed in our culture conditions. Our results
      suggest that EGF stimulates the proliferation of neural precursor cells that have
      the potential but differentiate randomly to catecholaminergic cells.

PMID- 8747162
TI  - The modulatory effect of melatonin on the dopamine-glutamate interaction in the
      anterior hypothalamus during ageing.
AB  - We investigated the effects of melatonin on the dopamine-glutamate interaction in
      the anterior hypothalamus of young, middle-aged and aged rats. In young rats,
      under the effects of amphetamine, melatonin produced an inhibition of dopamine
      release and a significant increase in glutamate and aspartate release. In middle
      aged and aged rats, the inhibitory effects of melatonin on amphetamine-evoked
      dopamine release were maintained, but no effects on glutamate or aspartate
      release were found. These results suggest that, during ageing, the modulatory
      effect of melatonin on dopamine release in rat anterior hypothalamus is preserved
      whereas the dopamine-glutamate interaction is disrupted with age.

PMID- 8747163
TI  - Potentiation by K+ of anoxic release of newly synthesized neuronal glutamate.
AB  - Glutamate synthesis from [14C]glutamine, release of newly synthesized, labelled
      glutamate and cell death in primary cultures of the glutamatergic cerebellar
      granule cell neurones under anoxic conditions were increased by an elevation of
      the extracellular potassium concentration. Phenylsuccinate, an inhibitor of
      transmitochondrial transport and hence of glutamate synthesis from glutamine,
      decreased the potassium-enhanced glutamate synthesis and the release of newly
      synthesized glutamate and reduced cell death. Since the extracellular
      concentration of potassium is elevated during brain anoxia and glutamate
      neurotoxicity is thought to contribute to neuronal cell death under this
      condition, these observations may be of functional and potentially therapeutic
      relevance.

PMID- 8747164
TI  - beta-Amyloid selectively augments NMDA receptor-mediated synaptic transmission in
      rat hippocampus.
AB  - The effect of beta-amyloid on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic
      excitatory postsynaptic currents measured with whole-cell voltage-clamp
      techniques, was investigated in the rat dentate gyrus in vitro. Application of
      beta-amyloid (1-40) by extracellular perfusion (200 nM) or intracellularly via
      the recording pipette (100 nM) resulted in a gradual enhancement of the NMDA
      receptor-mediated synaptic currents which did not reverse on washout. Basal AMPA
      receptor-mediated transmission, resting membrane potential or input resistance of
      the granule cells did not change. These results provide direct evidence that beta
      amyloid selectively interacts with the potentially neurotoxic NMDA receptor via a
      postsynaptic site. It is proposed that this action may help explain the synaptic
      changes seen in Alzheimer's disease.

PMID- 8747165
TI  - MRI of amygdala fails to diagnose early Alzheimer's disease.
AB  - We evaluated the ability of MRI of the amygdala to diagnose early Alzheimer's
      disease (AD). The volume of the amygdala was measured in 54 patients with
      probable AD, 38 subjects with age-associated memory impairment (AAMI), 34
      cognitively normal elderly controls (OC) and 20 young controls (YC). The amygdala
      was atrophied in all the elderly study groups with atrophy being strongest in the
      AD group (p < 0.0001). The OC and AAMI groups differed from the YC group (p <
      0.05) but not from each other. There was a major overlap between the study
      groups. The volumes also correlated with age (p < 0.0001) and gender (p < 0.001).
      A correct classification was achieved in 74% of AD patients and the non-demented
      elderly subjects. Thus, MRI of amygdala fails to diagnose AD accurately.

PMID- 8747166
TI  - Epibatidine and ABT 418 reveal selective losses of alpha 4 beta 2 nicotinic
      receptors in Alzheimer brains.
AB  - Subtypes of nicotinic acetylcholine receptors (nAChRs) were characterized in
      human temporal cortex and in a alpha 4 beta 2 nAChR-transfected M10 cell line
      using the nicotinic agonists epibatidine, ABT 418 and (-)nicotine in competition
      studies with [3H]nicotine and [3H]cytisine. The three agonists best fitted to an
      one-site model in M10 cells with the rank of potencies: epibatidine > > (-)
      nicotine > ABT 418. Heterogeneous nAChRs were revealed for epibatidine and ABT
      418 in the human temporal cortex. Both compounds labelled a major binding site
      (Ki 0.35 nM and 68.6 nM respectively) and an additional minor binding site with
      higher affinity (Ki 0.002 nM and 0.86 nM respectively). Corresponding data for (
      )nicotine were a major site (Ki 2.80 nM) and an additional minor site with lower
      affinity (Ki 2150 nM). Selective losses in the major population of nAChR were
      observed in the temporal cortex of brains from individuals with Alzheimer's
      disease with all three agonists. This suggested that the alpha 4 beta 2 nAChR
      subunit might be the most vulnerable in Alzheimer's disease (AD) and a possible
      target for therapeutic strategies.

PMID- 8747167
TI  - Single unit responses of the amygdala after conditioned taste aversion in
      conscious rats.
AB  - Amygdalar neuronal responses to sodium saccharin used as the conditioned stimulus
      (CS) and to other taste stimuli including sucrose, NaCl, HCl and quinine
      hydrochloride were recorded before and after the acquisition of conditioned taste
      aversion (CTA) in freely behaving rats. Of 73 units recorded from the basolateral
      nucleus of the amygdala (BLA), 17 (23%) and 1 (1%) exhibited facilitatory and
      inhibitory responses, respectively, to both the CS and sucrose after aversive
      conditioning to the CS. On the other hand, 3 (5%) and 11 (17%) of 64 units
      recorded from the central nucleus of the amygdala (Ce) exhibited facilitatory and
      inhibitory responses, respectively. The responsiveness of these BLA and Ce units
      to other taste stimuli did not change significantly. These findings that the
      facilitatory effect was dominant in the BLA, while the inhibitory effect was more
      frequent in the Ce suggest that the BLA and Ce are differentially involved in
      CTA.

PMID- 8747169
TI  - Evidence for inert gas narcosis mechanisms in the occurrence of psychotic-like
      episodes at pressure environment.
AB  - Psychotic-like episodes in divers exposed to high pressure have been attributed
      to either the high-pressure neurological syndrome, confinement in pressure
      chamber, the subject's personality, or the addition of nitrogen or hydrogen to
      the basic helium-oxygen breathing mixture used for deep diving. Alternatively, it
      is suggested that these disorders are in fact paroxysmal narcotic symptoms that
      result from the sum of the individual narcotic potencies of each inert gas in the
      breathing mixture. This hypothesis is tested against a variety of lipid
      solubility theories of narcosis. The results clearly support the hypothesis and
      provide new information about the cellular interactions between inert gases at
      raised pressure and pressure itself.

PMID- 8747168
TI  - Effects of aging on the expression of neurotrophins and their receptors in the
      rat pituitary gland.
AB  - We studied the effect of aging on the mRNA levels of neurotrophins and their
      receptors in the rat pituitary gland using in situ hybridization. In 2-month-old
      rats, mRNA for brain derived neurotrophic factor (BDNF) was observed in the
      anterior and intermediate lobes of the pituitary. TrkB and trkC, the putative
      receptors for BDNF and neurotrophin-3, were also expressed in the pituitary. In
      contrast, trk mRNA could not be detected in any of the pituitaries studied. Aging
      did not affect BDNF mRNA levels. In 2-year-old rats, trkB and trkC mRNA levels
      were decreased in the anterior lobe. TrkB mRNA levels decreased also in the
      neural lobe. These results show that although the expression of BDNF does not
      change during aging in the pituitary, expression of trkB and trkC mRNAs are
      altered in senescence. These changes may reflect overall impairments in pituitary
      endocrine functions in old age or they may be associated with morphological
      alterations in pituitary innervation.

PMID- 8747170
TI  - What does the hippocampus really do?
AB  - Much of the evidence used to implicate the hippocampus in learning and memory has
      been obtained from clinical cases and/or experimental studies with animals where
      the damage is extensive and includes more than just the hippocampus. When the
      damage is limited to the cells that comprise the hippocampus (CA1-CA3 pyramidal
      cells, hilar and granule cells in the dentate gyrus) the effect on behavior in
      the rat is more limited than what is usually reported. Selective, axon-sparing
      ibotenic acid lesions of the hippocampus were used in the experiments that are
      reviewed to study the effects of removing the hippocampus on: (1) the acquisition
      of spatial and non-spatial information; (2) complex, non-spatial representational
      learning; and (3) acquisition and utilization of contextual information. The
      results indicated that rats with the hippocampus removed were impaired on those
      tasks that require the utilization of spatial and contextual information but
      performed like controls in learning about and handling (even complex) non-spatial
      information. Future research utilizing selective lesions of the hippocampus and
      sensitive behavioral testing techniques should help clarify the extent to which
      the impairments in the acquisition of spatial information and the ability to
      utilize contextual, background cues can be reduced to a single, underlying
      learning process.

PMID- 8747171
TI  - Learning-related changes in hippocampal field potentials.
AB  - It is commonly believed that learning is based on modifications of synaptic
      strength. Much of the evidence for this comes from the observation that blockade
      of processes necessary for induction of long-term potentiation in the hippocampus
      also blocks certain forms of learning. As such correlations may have many causes,
      an understanding of the mechanisms for memory formation might also profit from
      direct recording of cellular activity in learning tasks. Field potential
      recording represents one such approach. Although changes in field potentials are
      unlikely to uncover modifications in synaptic strength related to the storage of
      memory, any general facilitation (or reduction) of synaptic transmission taking
      place in populations of neurons during the acquisition stage might be picked up
      by a field measure. One problem related to the approach is that field potentials
      are heavily affected by non-learning factors. It is shown that field potentials
      in the hippocampus are highly sensitive to changes in brain temperature and that
      a significant part of the increase in field excitatory postsynaptic potentials (f
      EPSPs) during learning reflects warming of the brain. Temperature-related changes
      in synaptic transmission do not affect the efficiency of spatial learning, as the
      acquisition of a water-maze task is equally efficient at low (30-32 degrees C)
      and high (37-39 degrees C) brain temperatures. Subtraction of the temperature
      component of the field potential alterations during learning in an exploration
      task shows that exploration is accompanied by a temperature-independent synaptic
      potentiation as well. Both the f-EPSP and the population spike are increased, and
      both decay gradually within 15-20 min. It is important to find out whether this
      potentiation reflects learning-related processes and whether such a potentiation
      is useful to the brain given the apparent 'noise' caused by temperature-related
      physiological changes.

PMID- 8747172
TI  - The role of mesolimbic dopaminergic and retrohippocampal afferents to the nucleus
      accumbens in latent inhibition: implications for schizophrenia.
AB  - Latent inhibition (LI) consists in a retardation of conditioning seen when the to
      be-conditioned stimulus is first presented a number of times without other
      consequence. Disruption of LI has been proposed as a possible model of the
      cognitive abnormality that underlies the positive psychotic symptoms of acute
      schizophrenia. We review here evidence in support of the model, including
      experiments tending to show that: (1) disruption of LI is characteristic of
      acute, positively-symptomatic schizophrenia; (2) LI depends upon dopaminergic
      activity; (3) LI depends specifically upon dopamine release in n. accumbens; (4)
      LI depends upon the integrity of the hippocampal formation and the
      retrohippocampal region reciprocally connected to the hippocampal formation; (5)
      the roles of n. accumbens and the hippocampal system in LI are interconnected.

PMID- 8747173
TI  - On the significance of brain extracellular uric acid detected with in-vivo
      monitoring techniques: a review.
AB  - The concentration of uric acid [UA] in the extracellular fluid (ECF) estimated
      with in-vivo voltammetry and microdialysis data is compared for probes of
      different diameters from the day of implantation (acute) to several days
      (chronic) or even months after surgery. For small probes (diameter < 160 microns)
      the acute [UA] of ca. 5 microM decreased significantly to ca. 1 microM under
      chronic conditions. For larger probes (e.g., 320-microns diameter) the acute [UA]
      was also ca. 5 microM, but this value significantly increased to ca. 50 microM
      under chronic conditions. Associated with this difference in [UA], there were
      parallel differences in the extent of gliosis around the probes. These findings
      are discussed in terms of possible sources of extracellular UA and their
      implications for in-vivo monitoring techniques in behaving animals.

PMID- 8747174
TI  - Physiological release of excitatory amino acids.
AB  - The contribution of in vivo monitoring to the study of glutamate release is
      reviewed. Physiological stimulation increases both glutamate and aspartate in the
      extracellular compartment of the brain and both amino acids show Ca(2+)-dependent
      K(+)-evoked release. However, the finding that only glutamate is stored in
      synaptic vesicles implies that glutamate is the excitatory transmitter. Released
      glutamate is taken up into both neurones and glia by glutamate transporters.
      Uptake of glutamate, in addition to clearing the synapse, has a number of
      additional functions. Uptake into glia leads to the release of glutamine, which
      is involved in the recycling of transmitter glutamate; uptake into both neurones
      and glia leads to the release of ascorbate; uptake into glia leads to an increase
      glycolysis and export of lactate, an energy substrate for neuronal metabolism.
      Reversal of the glutamate transporter accounts for the parallel release of
      glutamate and aspartate from the cytoplasmic compartment. The basal concentration
      of extracellular glutamate is in the micromolar range. Such levels could lead to
      desensitisation of both NMDA and non-NMDA receptors. The functional implications
      of the level of basal glutamate are difficult to assess at present in view of the
      existence of multiple glutamate receptor subunits with different functional
      properties and distributions.

PMID- 8747175
TI  - Voltammetric and microdialysis monitoring of brain monoamine neurotransmitter
      release during sociosexual interactions.
AB  - The monoamine neurotransmitters have long been ascribed important modulatory
      actions on male sexual behavior by a wealth of pharmacological studies.
      Methodological developments have now made possible the assessment of the
      extracellular levels of amine transmitters and their metabolites in discrete
      brain areas of sexually behaving animals using in vivo voltammetry and
      microdialysis. Studies in our and other laboratories consistently show increased
      dopamine release in forebrain structures known to be involved in mating activity,
      including the nucleus accumbens and the medial preoptic area, during both the
      appetitive (i.e., non-contact exposure to sexual stimuli) and consummatory phases
      of this behavior. Serotonin utilization seems to be mainly related to
      consummatory events. These findings are consistent with the pharmacological
      evidence as well as previous ex vivo work. The state of sexual inactivity that
      follows unrestricted mating associates with increased dopamine turnover in the
      preoptic area. According to the available information, it could reflect some
      blockade of dopaminergic receptors, possibly involving prolactin. No disturbance
      of ongoing sexual behavior was observed during the neurochemical monitoring
      sessions with either methodology. These studies show voltammetry and
      microdialysis as powerful complementary tools for the assessment of sociosexual
      interactions.

PMID- 8747176
TI  - Oculomotor activity and visual spatial attention.
AB  - Subjects made a horizontal or vertical saccade in response to a non-lateralized
      auditory stimulus. Simple manual reaction time (RT) for the detection of light
      targets at extrafoveal locations was modulated by the intention to make the
      saccade insofar as RT to targets presented at the saccadic goal location or in
      the hemifield containing that location was faster than RT to targets presented at
      the opposite, mirror-symmetric location. This RT difference was maximal prior to
      the beginning of the saccade and vanished after saccade termination, indicating
      that the effect was caused by the neural activity leading to the saccade rather
      than to the eye movement or the eye position per se. The results have
      implications for the understanding of the relations between visual spatial
      attention and oculomotor control, especially with regard to inhibitory phenomena
      arising from the non-correspondence between the line of sight and the focus of
      attention.

PMID- 8747177
TI  - There's more to colour than meets the eye.
AB  - Patients with cerebral achromatopsia, a perceptual disorder caused by
      ventromedial occipital brain damage, can be completely unable to arrange colours
      in chromatic sequence and fail most conventional tests of colour blindness. A
      possible explanation for cerebral achromatopsia is that the colour-opponent
      parvocellular (P) channel has been selectively and totally destroyed at the level
      of visual cortex, leaving vision to be mediated by the broad-band magnocellular
      (M) channel. The persistence of normal occipital visually evoked potentials, and
      preserved sensitivity to isoluminant chromatic gratings indicates that if this
      hypothesis is correct the destruction must occur beyond the striate cortex. We
      have shown that an achromatopsic subject can detect chromatic borders and
      construct shape from colour, and that he can even perceive the apparent direction
      of motion of a phase shifted isoluminant chromatic grating where perceived
      direction depends on knowing the sign of the colour diffence, i.e., which colour
      is which in the stripes. This and other evidence suggests that perhaps only one
      part of the cortical P channel has been destroyed. Does the critical area
      involved in achromatopsia correspond to cortical area V4 of monkeys, often
      implicated in processing wavelength? When Visual Area 4 is totally ablated in
      monkeys they have only a mild colour discrimination impairment and easily solve
      the colour ordering and colour selection tasks that an achromatopsic patient
      finds impossible. However, monkeys with ventromedial damage rostral to Area V4 do
      perform like achromatopsic patients, suggesting that the role of V4 in the
      perception of colour is still unclear and that the colour area of the human brain
      does not correspond to area V4.

PMID- 8747178
TI  - Covert orienting to non-informative cues: reaction time studies.
AB  - Lateralized, non-informative visual cues lengthen reaction time (RT) to
      successive targets flashed in the same hemified. Early ipsilateral RT
      facilitation is limited to the co-occurrence of cues and targets. Inhibition from
      visual cues has sensory components which do not depend on orienting, as well as
      attentional components which are limited to one side of the vertical meridian. An
      inhibition of RT to targets ipsilateral to the cues has been found with somatic
      or auditory cues and targets, and also when somatic targets follow visual cues or
      visual targets follow somatic cues. The results reviewed in this paper (1) are
      best accounted for by directional constraints in motor readiness which are
      induced by the voluntary suppression of an overt orienting toward the location of
      the cue; (2) indicate that similar mechanisms of covert orienting operate in the
      whole peripersonal and near extrapersonal space; and (3) point to a common neural
      substrate mediating both intramodal and cross-modal effects.

PMID- 8747179
TI  - Multiple mechanisms of visual-spatial attention: recent evidence from human
      electrophysiology.
AB  - Natural visual scenes contain vast quantities of information--far more than the
      visual system can process in a short period of time-and spatial attention is
      therefore used to focus the visual system's processing resources onto a subset of
      the incoming visual information. Most psychological theories of attention posit a
      single mechanism for this focusing of attention, but recent electrophysiological
      studies have provided evidence that the visual system employs several separable
      neural mechanisms of spatial attention. This paper describes the evidence for
      multiple attentional mechanisms and suggests links between these
      neurophysiologically defined mechanisms and specific functional processes that
      have been proposed in psychological theories of attention.

PMID- 8747180
TI  - Neural mechanisms for stimulus selection in cortical areas of the macaque
      subserving object vision.
AB  - The present article reviews some recent work on the neuronal mechanisms
      underlying space-based and feature-based stimulus selection in the primate
      occipito-temporal pathway of cortical visual processing. Clear evidence
      demonstrates that activity in areas V4 and IT is high for a stimulus which is
      selected either for its position in space or for its features, while it is
      considerably suppressed for other, irrelevant stimuli. Data are discussed within
      a conceptual framework whereby objects in the visual field always compete for
      focal resources. According to task demands, any kind of input (objects of a
      certain category, objects with a certain form, color or motion, objects at a
      certain location) can be behaviorally relevant. A short-term description (working
      memory) of the currently relevant object properties controls competitive bias in
      the visual system, such that inputs matching that description are favored to the
      disadvantage of task-irrelevant inputs. This framework emphasizes a tight, causal
      link between memory signals and mechanisms for stimulus selection in visual
      cortex. In all cases gating of neural activity was constrained by spatial
      factors. In area V4, responses to an ignored stimulus in the receptive field of
      the recorded neuron were maximally suppressed when the monkey attended to a
      second stimulus located within the boundary of the same receptive field, while
      suppression was virtually absent when attention was directed to a second stimulus
      well outside the receptive field border. In IT cortex, suppressed responses
      depended on both the selected and ignored stimuli being within the hemifield
      contralateral to the recorded hemisphere, while suppression was much reduced when
      the stimuli were presented across the vertical midline. These spatial constraints
      on the occurrence of modulation of visual responses may reflect limitations
      imposed by the local pattern of reciprocal inhibitory connections, which are
      supposed to underlie competitive interactions among objects in the field, that is
      among object representations in cortex.

PMID- 8747181
TI  - Object segmentation and visual neglect.
AB  - A major development in recent research on human visual attention has been the
      increasing interplay between research on normal attentional mechanisms, and
      accounts of unilateral neglect and extinction after brain-damage in terms of
      damage to these mechanisms. Although there are potential pitfalls in this
      approach, it has already proved useful. This is illustrated for the debate over
      whether segmentation processes precede spatial attention in vision. This debate
      began in the normal literature, but has since motivated several studies of visual
      neglect and extinction. These reveal that various segmentation processes can
      influence which region of a scene will be neglected or extinguished, implying
      that grouping may precede the abnormal bias in spatial attention, and showing
      that considerable residual processing can take place in the neglected or
      extinguished visual field. The extent of this residual processing is tentatively
      related to emerging anatomical data.

PMID- 8747182
TI  - Visual perception and phenomenal consciousness.
AB  - In the (re-)animated debate on consciousness we focus on three questions: Who has
      consciousness? What is its neuronal basis? What is its function? Regarding the
      first, we suggest that consciousness is exclusive to living organisms able to
      distinguish self from non-self. It may be restricted further to organisms who
      possess a repertoire of overt and covert behaviour which can be voluntarily
      modified and suppressed. This requires an intermediary neuronal net mediating
      between sensory input and behavioural output. What are the properties of this net
      which distinguish unalloyed information processing per se from conscious
      representation? To tackle this second question, we use the visual system and the
      functional losses that result from lesions at its different levels, and
      differentiate a reflexive, a phenomenal, and a consciously accessible stage of
      visual processing. We suggest that the latter two represent two distinct aspects
      of consciousness. Blindsight, a neurological example of visual processing in the
      absence of phenomenal vision, could help to elucidate the neuronal basis of
      phenomenality, and the special role of striate cortex. Like the patients, our
      monkeys with unilateral striate cortical removal show evidence not just of
      residual visual processing, but of the same absence of phenomenal vision, opening
      routes to further exploring the details of its neuronal implementation. The
      second aspect, conscious access to presently or previously processed information,
      is likely to require higher cortical structures, and may depend on the stage of
      phenomenal representations. In patients with blindsight, both aspects are lost,
      and it is conceivable that a loss of phenomenality generally causes a loss of
      conscious accessibility. One important function of phenomenal representations,
      our third question, would then be to allow conscious retrieval and manipulation
      of currently processed or formerly stored information, enabling organisms to
      consciously think and plan.

PMID- 8747183
TI  - Sensations and brain processes.
AB  - A hypothesis on the physiological conditions of consciousness is presented. It is
      assumed that the occurrence of states of consciousness causally depends on the
      formation of complex representational structures. Cortical neural networks that
      exhibit a high representational activity develop higher-order, self-referential
      representations as a result of self-organizing processes. The occurrence of such
      states is identical with the appearance of states of consciousness. The
      underlying physiological processes can be identified. It is assumed that neural
      assemblies instantiate mental representations; hence consciousness depends on the
      rate at which large active assemblies are generated. The formation of assemblies
      involves the activation of the N-methyl-D-aspartate receptor channel complex
      which controls different forms of synaptic plasticity including rapid changes of
      the connection strengths. The various causes of unconsciousness (e.g.,
      anaesthetics or brain stem lesions) have a common denominator: they directly or
      indirectly inhibit the formation of assemblies.

PMID- 8747184
TI  - Layer I of primary sensory neocortex: where top-down converges upon bottom-up.
AB  - A fundamental paradigm shift is underway in the behavioural neurosciences which
      promotes renewed discussion of neural correlates of conscious sensation. A
      growing body of evidence that the primary sensory areas are central to conscious
      processing is inconsistent with conventional bottom-up models of passive sensory
      transformation. The new paradigm emphasizes the interaction of top-down
      corticocortical influences with bottom-up sensory feedback. This review develops
      the new interactive paradigm with respect to the behaviourally relevant N1
      component of the somatosensory evoked response in primary somatosensory neocortex
      which is only observed during conscious states and predicts touch discrimination
      behaviour. N1 is generated by layer I excitation apparently in response to
      backward projections from higher order cortical areas. The backward
      corticocortical projections mediating top-down influences are anatomically
      concentrated in layer I where they strongly excite the subpopulation of pyramidal
      neurons with extensive distal apical dendrites. This subpopulation includes the
      forward-projecting pyramids subserving corticocortical reentrance as well as the
      corticobulbar projections mediating cortical control over fine sensory-oriented
      movements. This interactive paradigm views conscious sensation as an active
      behaviour with the optimal spatial resolution of primary areas serving as the
      sensory-motor interface at the major convergence point between reentrant bottom
      up and top-down pathways. A device is proposed for the reconstruction of cortical
      sensory processing based upon the central importance of the primary area as the
      focus of convergent top-down cortical projections.

PMID- 8747185
TI  - The problem of animal consciousness in relation to neuropsychology.
AB  - It is argued that experimental analyses of changes in sensory awareness require
      not only a measure of discrimination, but a separate commentary or classificatory
      judgment by subject. In human blindsight there is a dissociation between
      successful discrimination, on the one hand, and a commentary which acknowledges
      no awareness of the discriminanda, on the other. Comparable judgments should be
      possible, in principle, in animal studies of blindsight and other neurological
      dissociations in which there is retention of function in the absence of
      awareness. Important animal studies are beginning to appear along these lines.
      Such a procedure also always entails an assumption of normal "awareness". A
      complementary approach for some situations is the study of intentionality in the
      context of altered goals.

PMID- 8747186
TI  - Potentiation of a slow Ca(2+)-dependent K+ current by intracellular Ca2+
      chelators in hippocampal CA1 neurons of rat brain slices.
AB  - 1. In hippocampal CA1 neurons of rat brain slices, a Ca(2+)-dependent slow
      afterhyperpolarization (sAHP) and underlying K+ current (IsAHP) are activated by
      Ca2+ influx and presumably reflect the time course of the intracellular Ca2+
      signal produced by neuronal stimulation. We tested the hypothesis that when
      exogenous Ca2+ chelators become the predominant mobile Ca2+ buffer in the neuron,
      they alter the shape of intracellular Ca2+ signals responsible for IsAHP. The
      nature of this alteration provides insight into the mechanism of IsAHP
      generation. 2. Derivatives of 1,2-bis-[2-amino phenoxy] ethane N,N,N',N'
      tetraacetic acid (BAPTA) with different dissociation constants (KDS) for Ca2+
      ranging from 0.15 to 7,000 microM were used to test this hypothesis. We also
      examined the effects of ethylene glycolbis (beta-aminoethyl either)-N,N,N',N'
      tetraacetic acid (EGTA), which has a KD similar to that of BAPTA for Ca2+, but
      which binds and releases Ca2+ 100 times more slowly. When delivered to the
      cytoplasm by dialysis from a patch pipette, these chelators potentiated,
      inhibited, or had no effect on IsAHP depending on their concentration, affinity,
      and binding kinetics. 3. IsAHP decayed exponentially over much of its time
      course, with a half-decay time of 0.9 +/- 0.1 s (mean +/- SE, n = 22).
      Immediately after breakthrough into the whole cell configuration, there was an
      initial period of approximately 5 min during which IsAHP magnitude increased
      approximately 3.5-fold with no change in time course. Thereafter, the time course
      and amplitude of IsAHP were stable for > 45 min. 4. Addition of 1 mM of the high
      affinity chelators 5,5'-dimethyl BAPTA or BAPTA to the pipette solution first
      increased the decay time of IsAHP 1.5-fold. However, within 10-15 min after break
      through, the current was abolished. Addition of Ca2+ (0.1-1.0 mM) to the patch
      pipette containing the BAPTA derivatives reduced the ability of a given
      concentration of high-affinity chelator to inhibit IsAHP and also prolonged the
      period of IsAHP enhancement. A similar prolongation of the period of enhancement
      with even less attenuation of IsAHP was apparent with 0.1 mM 5,5'-dimethyl BAPTA
      and 0.1 mM Ca2+. 5. The intermediate-affinity chelator 4.4'-difluoro BAPTA (1 mM)
      prolonged the decay phase of the sAHP/IsAHP without attenuating the current. A
      twofold prolongation of IsAHP also was observed in neurons dialyzed with internal
      solution containing 3 mM EGTA and 0.3 mM Ca2+. Dialysis with 1 mM of the low
      affinity chelators 2-amino-5-fluorophenol-N,N,O-triacetic acid (5-fluoro APTRA)
      or 5,5'-dinitro BAPTA had no apparent effect on IsAHP. All of the chelators that
      prolonged the decay phase of IsAHP also induced a rising phase such that a well
      defined peak of IsAHP could be discerned at approximately 0.6 s after the end of
      the stimulus used to evoke the current. 6. Weak stimulation of muscarinic
      receptors selectively inhibits IsAHP. Thus the uncontaminated time course of
      IsAHP can be deduced by subtracting currents recorded before and after such
      muscarinic stimulation. With minimal exogenous buffer in the pipette (0.1 mM
      EGTA), the muscarinic-receptor-sensitive current exhibited a rising phase lasting
      approximately 300 ms and then decayed with a half-time of approximately 1 s. Both
      the rising and decay phases of the muscarinic-receptor-sensitive current were
      prolonged at least twofold by dialysis with BAPTA or 4,4'-difluoro BAPTA. Thus
      the effect of the chelators on the time course of IsAHP is not simply and
      artifact of inhibition of early components of the outward current. 7. The effects
      of BAPTA analogues on the time course of IsAHP are not due to changes in
      mobilization of intracellular Ca2+. External application of caffeine (10 mM),
      ryanodine (20 microM), dantrolene (20 microM), or thapsigargin (100 microM) had
      no effect on IsAHP recorded with the standard pipette solution or

PMID- 8747187
TI  - Regional characteristics of the membrane response of an identified crayfish
      nonspiking interneuron to intracellularly injected current.
AB  - 1. We investigated the membrane response of the local directionally selective
      (LDS) interneuron, a nonspiking cell identified in the terminal abdominal
      ganglion of crayfish, to intracellularly injected current in different regions
      within the cell by single-electrode, discrete current-clamp experiments. The site
      of electrode impalement into the cell was visualized in situ together with the
      cell structure under a dissecting microscope. 2. The LDS interneuron has
      dendritic branches on both hemiganglia connected by a thick segment crossing the
      midline. Irrespective of the site of electrode impalement, the interneuron showed
      outward rectification upon depolarization from the resting potential level. When
      hyperpolarizing current was injected, a linear relationship was observed between
      the voltage response of the interneuron and the amount of injected current. Upon
      large hyperpolarization, however, the interneuron showed inward rectification. 3.
      The input resistance of the interneuron measured within the linear range of the
      membrane response was significantly lower in the transverse segment than in
      lateral dendrites (0.001 < P < 0.01). The time constant of the transient voltage
      response to step current injection was also significantly shorter in the
      transverse segment than in the lateral dendrites (0.001 < P < 0.01). 4. Although
      the regional difference in the input resistance could be accounted for, at least
      partly, by different geometric conditions of each dendritic branch into which
      current was injected, the regional difference in the time constant of the
      membrane response cannot be accounted for by structural differences because the
      time constant is independent of the membrane area. It is thus suggested that the
      passive properties of the interneuron membrane that are related to its response
      time constant show regional variability within the cell.

PMID- 8747188
TI  - Neurotransmitters acting via different G proteins inhibit N-type calcium current
      by an identical mechanism in rat sympathetic neurons.
AB  - 1. We studied the mechanism of voltage-dependent inhibition of N-type calcium
      current by norepinephrine (NE) and vasoactive intestinal peptide (VIP) in adult
      rat superior cervical ganglion (SCG) neurons using the whole cell patch-clamp
      technique. 2. The voltage dependence of inhibition is manifest in the reversal of
      inhibition by strong depolarization. We tested the hypothesis that this voltage
      dependence results from disruption of G proteins binding to calcium channels.
      According to this hypothesis, the kinetics of calcium current reinhibition
      following a strong depolarization should become faster for higher concentrations
      of active G proteins. 3. Assuming that larger inhibitions result from higher
      concentrations of active G proteins, we used different concentrations of NE to
      alter the amplitude of inhibition and, thus, the active G protein concentration.
      We found that the kinetics of reinhibition at -80 mV following a depolarizing
      pulse to +80 mV were faster for larger inhibitions. 4. VIP induces voltage
      dependent inhibition of N-current via a different G protein (Gs) than that of NE
      (Go). We found that the effect of VIP on reinhibition kinetics was identical to
      that produced by NE. 5. Combined application of NE and VIP did not greatly
      increase the amplitude of the inhibition but significantly increased the rate of
      reinhibition. Thus NE plus VIP appear to greatly increase the concentration of
      the molecule binding to the channel (G protein according to the hypothesis). 6.
      The kinetics of calcium current disinhibition during strong depolarization (step
      to +80 mV) did not change with the size of the inhibition induced by NE, VIP or
      application of NE and VIP together. 7. Both the concentration-dependent
      reinhibition kinetics and concentration-independent disinhibition kinetics are
      consistent with the hypothesis that active G proteins bind directly to N-type
      calcium channels to modulate their activity in rat sympathetic neurons.

PMID- 8747189
TI  - Inwardly rectifying potassium conductance can accelerate the hyperpolarizing
      response in retinal horizontal cells.
AB  - 1. We studied the activation properties and assessed the functional role of the
      inwardly rectifying potassium conductance (GK.IR) in acutely isolated retinal
      horizontal cells (HCs) with the use of the whole cell patch-clamp technique. 2.
      The potassium current mediated by GK.IR was isolated by the use of Cs+ or Ba2+
      ions. This current was outward, although relatively small in amplitude, in the
      voltage range between the potassium equilibrium potential (EK) and 50-60 mV more
      positive. The current reversed its polarity at EK and became inward at potentials
      more negative than EK. When HCs were bathed in normal Ringer (EK = -90 mV), GK.IR
      began to active at about -30 mV, was 30-40% activated at the resting potential (
      70 to -80 mV) and about fully activated at -130 mV. Thus a significant portion of
      the activation range of GK.IR overlaps the HC physiological response range (-20
      to -80 mV). 3. GK.IR has a dramatic effect on the kinetics of membrane
      polarization. Blocking GK.IR with Cs+ or Ba2+ significantly slowed the rate of
      membrane hyperpolarization in response to a hyperpolarizing current ramp over the
      HC physiological response range. Blocking GK.IR also dramatically slowed the
      onset rate of a simulated light response generated by a brief break in a
      sustained glutamate puff. 4. These results suggest that GK.IR can enhance the
      temporal resolution of the HC by accelerating the onset rate of the
      hyperpolarizing light response.

PMID- 8747190
TI  - Kinematic analysis of cat hindlimb stepping.
AB  - 1. The purpose of this study is to analyze the kinematics of stepping from the
      point of view of limb control by attempting to dissociate the various neuronal
      and mechanical factors that shape actual movements observed experimentally. The
      cat hindlimb, like the primate arm, is a multijointed mechanical system with
      redundant degrees of freedom. We contend that a number of issues studied in the
      context of arm movement control, such as end point control and trajectory
      planning, may also be applicable to limb movement in locomotion. 2. We recorded
      and analyzed the kinematics of cat hindlimb movement in unrestrained over-ground
      locomotion at various speeds and with a variety of surface conditions. We found
      we could represent limb movement in the step cycle simply and concisely by the
      trajectories of the limb segment orientation angles. Each trajectory conformed to
      a monophasic sawtoothlike waveform, and the relative timing between segments was
      largely invariant in the range of movements studied. This contrasts with the
      representation using relative joint angles, as in Philippson's scheme, which
      exhibits a monophasic waveform at the hip but biphasic waveforms at the knee and
      ankle. 3. To investigate how whole limb kinematics, i.e., changes in the length
      and orientation of the whole limb, relates to that of the limb segments, we
      reconstructed limb movement from segment trajectories, assuming as a first
      approximation that they were indeed sawtooth wave forms. The result strongly
      suggested that the relative timing of segment movements played an important role
      in regulating limb length during the swing phase of the step cycle. A strong
      correlation between segment relative timing and changes in limb length was also
      observed experimentally. 4. A comparison between reconstructed and actual limb
      movement revealed two major differences. In contrast with the actual movement,
      which exhibited at least two extension phases and limb shortening during the
      stance phase, the reconstructed movement had only a single extension phase and no
      limb shortening. The discrepancies were fully accountable, however, by the limb
      ground interaction in stance, indicating that the features present in the actual
      movement resulted from the limb-ground interaction rather than from any
      elaborated control by the nervous system. 5. A second difference between
      reconstructed and actual movements was evident in an apparent jerkiness of the
      former and a difference in the hindpaw paths during the swing phase. These
      differences could be accounted for by including the consequences of limb inertia
      and finite muscle power, namely a gradual rather than instant change in velocity.
      Using a bell-shaped velocity profile for the segment movements, we were able to
      accurately reconstruct limb kinematics during the swing phase. 6. We conclude
      from this analysis that the overall features of limb kinematics in stepping may
      be controlled by regulating a small set of parameters related to the orientation
      angles of the limb segments. Specifically, the position of the endpoint, the
      hindpaw in this case, may be determined by the relative timing and amplitudes of
      segment trajectories. The point-by-point details of the observed limb kinematics
      may be largely attributed to limb mechanics and the interaction of the limb with
      its environment. Thus the neural control may be simpler than the kinematics
      suggests.

PMID- 8747191
TI  - Intrinsic neuromodulation in the Tritonia swim CPG: serotonin mediates both
      neuromodulation and neurotransmission by the dorsal swim interneurons.
AB  - 1. Neuromodulation has previously been shown to be intrinsic to the central
      pattern generator (CPG) circuit that generates the escape swim of the nudibranch
      mollusk Tritonia diomedea; the dorsal swim interneurons (DSIs) make conventional
      monosynaptic connections and evoke neuromodulatory effects within the swim motor
      circuit. The conventional synaptic potentials evoked by a DSI onto cerebral
      neuron 2 (C2) and onto the dorsal flexion neurons (DFNs) consist of a fast
      excitatory postsynaptic potential (EPSP) followed by a prolonged slow EPSP. In
      their neuromodulatory role, the DSIs produce an enhancement of the monosynaptic
      connections made by C2 onto other CPG circuit interneurons and onto efferent
      flexion neurons. Previous work showed that the DSIs are immunoreactive for
      serotonin. Here we provide evidence that both the neurotransmission and the
      neuromodulation evoked by the DSIs are produced by serotonin, and that these
      effects may be pharmacologically separable. 2. Previously it was shown that bath
      applied serotonin both mimics and occludes the modulation of the C2 synapses by
      the DSIs. Here we find that pressure-applied puffs of serotonin mimic both the
      fast and slow EPSPs evoked by a DSI onto a DFN, whereas high concentrations of
      bath-applied serotonin occlude both of these synaptic components. 3. Consistent
      with the hypothesis that serotonin mediates the actions of the DSIs, the
      serotonin reuptake inhibitor imipramine prolongs the duration of the fast DSI-DFN
      EPSP, increases the amplitude of the slow DSI-DFN EPSP, and increases both the
      amplitude and duration of the modulation of the C2-DFN synapse by the DSIs. 4.
      Two serotonergic antagonists were found that block the actions of the DSIs.
      Gramine blocks the fast DSI-DFN EPSP, and has far less of an effect on the slow
      EPSP and the modulation. Gramine also diminishes the depolarization evoked by
      pressure-applied serotonin, showing that it is a serotonin antagonist in this
      system. In contrast, methysergide greatly reduces both the slow EPSP and the
      modulation evoked by the DSIs, but has mixed effects on the fast EPSP.
      Methysergide also blocks the ability of exogenous serotonin to enhance the C2-DFN
      EPSP, demonstrating that it antagonizes the serotonin receptors responsible for
      this modulation. 5. Taken together with previous work, these results indicate
      that serotonin is likely to be responsible for all three actions of the DSIs that
      were examined: the fast and slow DSI-DFN EPSPs and the neuromodulation of the C2
      DFN synapse. These results also indicate that the conventional and
      neuromodulatory effects of the DSIs may be pharmacologically separable. In future
      work it may be possible to determine the functional role of each in the swim
      circuit.

PMID- 8747192
TI  - Axonal projections of caudal ventrolateral medullary and medullary raphe neurons
      with activity correlated to the 10-Hz rhythm in sympathetic nerve discharge.
AB  - 1. This is the first study to map the axonal projections of medullary neurons
      that are elements of the network responsible for the 10-Hz rhythm in sympathetic
      nerve discharge (SND) of urethan-anesthetized cats. Spike-triggered averaging and
      coherence analysis were used to identify caudal ventrolateral medullary (CVLM)
      and medullary raphe neurons with activity correlated to this component of SND.
      Spike-triggered averaging showed that CVLM neurons fired significantly earlier
      (17 ms on the average) than raphe neurons during the 10-Hz slow wave in inferior
      cardiac postganglionic SND. This observation raised the possibility that CVLM
      neurons are a source of the discharges of raphe neurons that are correlated to
      SND. 2. Nineteen of 47 CVLM neurons with activity correlated to the 10-Hz rhythm
      in SND were antidromically activated by micro-stimulation of the raphe. The
      longest onset latency of antidromic activation was 19.9 +/- 2.8 (SE) ms, a value
      comparable with the difference in firing times of CVLM and raphe neurons during
      the naturally occurring 10-Hz slow wave in inferior cardiac SND. In most cases
      the response likely reflected activation of an axonal branch of the CVLM neuron,
      because the onset latency of antidromic activation could be changed dramatically
      by moving the stimulating microelectrode as little as 0.2 mm within the raphe.
      Also, the onset latency of antidromic activation of nine CVLM neurons was
      significantly shortened (25.0 +/- 2.5 vs. 16.7 +/- 2.7 ms) when the stimulus
      intensity was raised above threshold. 3. The hypothesis that the axons of CVLM
      neurons with activity correlated to the 10-Hz rhythm in SND terminated on and
      excited raphe neurons was supported by the following observations. First, CVLM
      neurons could not be antidromically activated by stimuli applied to sites in
      tracks located 1.5-2 mm lateral to the midline, contralateral to the neuronal
      recording site; thus their axons did not cross the midline. Second, some CVLM
      neurons could be antidromically activated by stimuli applied to sites in only one
      of the tracks through the midline; thus it is unlikely that their axons were
      destined for more rostral or caudal portions of the brain stem. Third, 37% of the
      raphe neurons with activity correlated to the 10-Hz rhythm were synaptically
      activated by microstimulation of the CVLM, with a minimum onset latency of 18.1
      +/- 2.6 ms. This value was not significantly different than the longest onset
      latency of antidromic activation of CVLM neurons by raphe stimulation. 4. CVLM
      neurons with activity correlated to the 10-Hz rhythm in SND could not be
      antidromically activated by microstimulation of the rostral ventrolateral medulla
      (RVLM) or thoracic spinal cord. Thus CVLM neurons are not a direct source of the
      10-Hz discharges of RVLM or preganglionic sympathetic neurons. 5. Eight of 41
      raphe neurons with activity correlated to the 10-Hz rhythm in SND were
      antidromically activated by microstimulation of the CVLM. The latency of the
      antidromic response of six raphe neurons was shortened from 15.2 +/- 3.1 to 11.9
      +/- 3.1 ms by raising stimulus current above threshold, implying the existence of
      local axonal branching. The onset latency of antidromic activation of five raphe
      neurons was changed by moving the stimulating microelectrode within the CVLM. 6.
      The axons of at least some of these raphe neurons likely terminated in the CVLM,
      because higher current was required to antidromically activate these neurons from
      sites in a track located 0.5 mm further laterally, and they were not
      antidromically activated by microstimulation of the RVLM. Also 32% of the CVLM
      neurons were either excited or inhibited by microstimulation of the raphe. The
      minimum onset latency of synaptic activation (18.3 +/- 4.2 ms) or inhibition (10
      20 ms) of CVLM neurons by raphe stimulation was similar to the longest onset
      latency of antidromic activation of raphe neurons by CVLM microstimulation. 7.
      These data are consistent with the view

PMID- 8747193
TI  - Properties of motor units after self-reinnervation of the cat superior oblique
      muscle.
AB  - 1. The mechanical properties of motor units of the cat superior oblique muscle
      and axonal conduction velocities of trochlear motoneurons have been studied at
      several postoperative times after intracranial axotomy of the trochlear nerve. 2.
      Whole muscle twitch forces were generally within the normal range by
      approximately 4 mo postoperative, indicating that reinnervation is complete at
      this time. 3. Among animals studied 3.5-4.5 months after trochlear axotomy,
      average motor-unit tetanic forces were increased by a factor of approximately 2.5
      compared with units studied in normal superior oblique muscle. Average motor-unit
      tetanic forces in animals studied 14.5-23 mo after axotomy were also increased
      relative to normal, but the difference was not significant. Among all
      reinnervated motor units, there was a tendency for increased twitch time-to-peak
      relative to control. Reinnervated motor-unit fatigue properties were similar to
      normal. 4. Average trochlear motoneuron conduction velocities for animals at all
      postoperative intervals remained significantly lower than the average conduction
      velocities from three of four normal animals. 5. Counts of Nissl-stained cell
      bodies in axotomized and control, contralateral trochlear nuclei showed that some
      cell loss had occurred, averaging approximately 17% 3.5-4.5 mo postoperative and
      24% 14.5-23 mo postoperative. Associated with this loss was an increase (10%) of
      axotomized motoneuron soma cross-sectional area. 6. Muscle fiber cross-sectional
      areas (CSA) were measured in reinnervated superior oblique muscles and compared
      with CSAs from contralateral, control muscles. Average CSA was significantly
      decreased in all reinnervated muscles, with the relative decreases ranging from
      approximately 10 to 28%. 7. The results are discussed in terms of factors that
      determine motor-unit force; muscle fiber CSA, specific force, and innervation
      ratio. We conclude that the increases of average motor-unit force in short-term
      reinnervated superior oblique muscles are most likely related to polyneuronal
      innervation of muscle fibers and that the return of these forces to normal levels
      in long-term muscles is related to synapse elimination. Our results are compared
      with those of other self-reinnervation studies, and the potential role played by
      the time muscle remains denervated in determining the persistence of polyneuronal
      innervation after reinnervation is considered.

PMID- 8747194
TI  - Passive compliance and active force generation in the guinea pig outer hair cell.
AB  - 1. Cochlear outer hair cells 20-80 microns in length were compressed axially in
      vitro using calibrated glass fibers mounted on a piezoelectric actuator. 2. When
      driven by rectangular pulses in the compression direction, the motion of the
      fiber tip consisted of a rapid initial compression that was complete in 10-20 ms
      followed by a smaller compression of slower time course. 3. The initial fiber
      deflections were found to be linear in amplitude for compressions up to 400 nm.
      The axial compliances of outer hair cells were calculated from the difference
      between the fiber tip motions when unattached and when in contact with a cell.
      Axial compliances were found to be in the range of 0.04-1.2 km/N for 149 cells.
      The axial compliance was an increasing function of cell length. 4. The peak
      forces generated by electrically stimulated outer hair cells were measured from
      the deflection of a glass fiber when the cells were stimulated by sinusoidal
      voltage commands. The slope gains of force generation (force generated per mV of
      command at the cell membrane) were estimated to range from 0.01 to 100 pN/mV.
      Most of the results fell in the range of 0.1-20 pN/mV. 5. When the apparent
      stiffness of the fiber was increased by moving the cell closer to the fiber base,
      the peak amplitude of the fiber deflection generated by the cell decreased and
      the peak force increased, for the same sinusoidal voltage command. 6. The results
      of the previous experiment were interpreted in the light of a model of outer hair
      cell motility in which an ideal extension generating element is in series with an
      internal stiffness element. This internal stiffness was then calculated for 13
      cells. 7. The internal stiffnesses of cells calculated by the above procedure
      were found to be positively correlated with the axial stiffness measurements
      obtained for the same cells. 8. The implications of the above results for the
      effectiveness of outer hair cell motility in vivo are discussed.

PMID- 8747195
TI  - Recruitment of GABAA inhibition in rat neocortex is limited and not NMDA
      dependent.
AB  - 1. The recruitment of evoked fast inhibitory postsynaptic currents (IPSCs) and
      excitatory postsynaptic currents (EPSCs) was examined using whole cell voltage
      clamp recordings from layer V pyramidal neurons in slices of rat somatosensory
      cortex. Synaptic currents were evoked with graded electrical stimulation to
      assess the relative activation of IPSCs and EPSCs. Fast GABAA ergic IPSCs were
      selectively recorded by holding cells at potentials equal to EPSC reversal
      (approximately 0 mV). EPSCs were likewise isolated by holding cells at IPSC
      reversal potential (about -75 mV). 2. As stimulus intensities were increased, the
      magnitude of the postsynaptic currents also increased. Over the range of stimuli
      applied (2-10 V), EPSCs did not exhibit an upper limit. However, fast gamma
      aminobutyric acid-A (GABAA-mediated IPSCs reached a maximum at intensities
      approximately 2 times threshold. 3. The limit on fast inhibition was unresponsive
      to alterations in N-methyl-D-aspartate (NMDA)-mediated excitation. Exposure to
      nominally magnesium-free solutions or to the NMDA antagonist 3-[(RS)-2
      carboxypiperazin-4-yl]-propyl-1-phosphonic acid did not affect the fast IPSC
      maximum. Shifts in the input-output curves for submaximal activation of IPSCs
      were seen, which were attributed to polysynaptic excitation. 4. Blockade of alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (non-NMDA) receptors
      with 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) completely abolished
      synaptically driven, fast GABAA-mediated inhibition. These findings suggested
      that neocortical inhibitory cells could be driven exclusively through non-NMDA
      transmission. 5. By comparison, in hippocampal CA1 pyramidal neurons maximal fast
      inhibition was sensitive to both NMDA and non-NMDA receptor blockade. 6. The
      results in neocortex were corroborated by direct intracellular recordings from
      layer V-VI interneurons. Non-NMDA receptor blockade with CNQX prevented synaptic
      activation of action potentials in these cells, even during cotreatment with
      magnesium-free solution. 7. Together, these results suggest that recruitment of
      GABA(A) ergic IPSCs in neocortex is ultimately driven via glutamatergic afferents
      arriving at non-NMDA receptors on interneurons. Properties limiting fast
      inhibition would favor the propagation of enhanced excitatory activity through
      the neuronal network.

PMID- 8747196
TI  - Morphology of functional long-ranging primary afferent projections in the cat
      spinal cord.
AB  - 1. A beta-cutaneous primary afferent fibers were impaled in the dorsal columns of
      alpha-chloralose-anesthetized cats. Penetrations were made with the use of
      electrodes filled with 2 or 5% N-(2-aminoethyl) biotinamide hydrochloride
      (Neurobiotin, NB) in 0.1 or 1 M KCl. After determining its adequate stimulus,
      each fiber was activated by current pulses (18 Hz) injected via the
      microelectrode. The resulting cord dorsum potential (CDP) was recorded at four
      locations. NB was then injected into the fiber with the use of positive current
      pulses (11-22 nA) and a 75% duty cycle. 2. After allowing 2-8 h for diffusion,
      animals were perfused with saline (37 degrees C) followed by 4% paraformaldehyde
      (4 degrees C). Frozen 50-microns sections were cut in either the transverse or
      sagittal plane, processed on slides with the use of standard avidin-biotin
      protocols, and visualized by the nickel-enhanced diaminobenzidine (DAB) reaction.
      3. A total of 15 A beta-cutaneous afferents innervating both rapidly (RA) and
      slowly adapting (SA) receptors were adequately stained and their central
      projections recovered. For selected fibers the rostrocaudal and laminar bouton
      distributions were determined and compared with the distribution of monosynaptic
      CDP amplitudes recorded at the four surface locations. 4. The rostrocaudal extent
      of a single A beta-afferent fiber bouton distribution visualized with NB ranged
      from 8 to 17.5 mm (14.4 +/- 2.4 mm, mean +/- SD), or two to three times greater
      than that previously shown with the use of horseradish peroxidase (HRP). 5. The
      strong correlation between the rostrocaudal distribution of boutons and
      monosynaptic CDP amplitudes, and the improved agreement between modeled and
      observed CDP amplitudes over that seen previously with the use of HRP (mean
      percent error, HRP = 23 +/- 2.9%; NB = 9 +/- 2.3%), suggest that boutons along
      the entire length of the visualized distribution contribute to the recorded
      potentials. 6. Taken together, these findings suggest that inputs from a given
      point on the skin can directly influence sensory information processing over a
      much greater rostrocaudal extent than predicted by dorsal horn somatotopic maps.
      These findings are discussed in terms of their implications for spinal cord
      plasticity.

PMID- 8747197
TI  - Expression of LTP by AMPA and/or NMDA receptors is determined by the extent of
      NMDA receptors activation during the tetanus.
AB  - 1. We have tested, in CA1 hippocampal slices, the hypothesis that the expression
      of long-term potentiation (LTP) by alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) and/or N-methyl-D-aspartate (NMDA) receptors
      depends on the degree of NMDA receptors activation during the tetanus. 2. Slices
      were perfused in an artificial cerebrospinal fluid (ACSF) containing glycine (1
      microM), bicuculline (5 microM) and a low Mg2+ concentration (0.3 mM). To measure
      the AMPA and NMDA receptor-mediated field excitatory postsynaptic potential
      (fEPSPA and fEPSPN, respectively), we have used the following procedure: control
      fEPSPA was first measured, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM)
      was then added, and fEPSPN was evoked. CNQX was washed, and once control fEPSPA
      was recorded, the Schaffer collaterals were tetanized at a weak or a strong
      intensity. The slope of fEPSPA was measured for 30-45 min followed by that of
      fEPSPN after the application of CNQX. 3. At a weak intensity (TW, which
      corresponds to a fEPSPA of approximately 0.3 mV of amplitude and no fEPSPN), the
      tetanic stimulation generated LTP of fEPSPA (58.7 +/- 8.1% mean +/- SE, n = 9)
      but no significant potentiation of the fEPSPN (11.2 +/- 2.2%, n = 9). These
      values were significantly different (P < 0.05, analysis of variance, Fisher
      test). 4. In 9 of 13 slices, tetanic stimulation of strong intensity (Ts,
      intensity corresponding to a fEPSPN of approximately 0.3 mV of amplitude)
      generated LTP of fEPSPN (89.1 +/- 17.2%) but not of fEPSPA (9.44 +/- 2.8%). In
      the four remaining slices the tetani induce LTP of both fEPSPA and fEPSPN (81.7
      +/- 14.7% and 101 +/- 35.6%, respectively, both values were not significantly
      different). 5. We then examined the effects of decreasing fEPSPN by 50% in LTP
      generated by Ts and Tw. In the presence of 7-Chlorokynurenate (7Cl(-)-Kyn; 6
      microM; n = 6), an antagonist of the allosteric glycine site of the NMDA
      receptors, Ts generated LTP of fEPSPA (63.2 +/- 8.2%) but not of fEPSPN (12.6 +/-
      4.0%). Both values were significantly different. Tw still evoked LTP of fEPSPA
      but of smaller magnitude (29.8 +/- 6.3%, n = 8) than the one obtained in the
      absence of the antagonist (58.7 +/- 8.1%). Both values were significantly
      different. 6. The present observation suggests that l) LTP of fEPSPA has a lower
      threshold than that of fEPSPN, i.e., stronger activation of NMDA receptors during
      the tetani is required to induce LTP of fEPSPN than the one required for inducing
      LTP of fEPSPA; and 2) there is a bell-shaped relationship between the degree of
      activation of NMDA receptors during the tetani and the magnitude of LTP of the
      fEPSPA: tetani that generate LTP of fEPSPN have a low probability to induce LTP
      of fEPSPA. We suggest that AMPA and NMDA components are potentiated through two
      different presumably postsynaptic processes.

PMID- 8747198
TI  - Intracellular recordings from intramural neurons in the guinea pig urinary
      bladder.
AB  - 1. Intracellular recordings were made from intramural neurons in the urinary
      bladder of guinea pigs. 2. The neurons were located in two types of ganglia:
      those where the cells were densely packed and those where the neurons were
      loosely packed. Staining of the cells by intracellular injections of markers
      showed that the cells had between one to three long processes and several short
      dendrites. 3. The resting potential measured in 230 neurons was -55.20 +/- 0.67
      (SE) mV, and the input resistance was 58.37 +/- 1.78 M omega. 4. Injection of
      depolarizing currents from the recording electrode evoked two types of firing
      patterns. In 86.2% of the neurons, depolarizing currents evoked a prolonged
      firing of action potentials (tonic cells). In the rest of the neurons, a
      depolarization elicited one to three action potentials only (phasic cells). In
      all the cells tested, the action potentials were reversibly blocked by
      tetrodotoxin (TTX; 1 microM). In the presence of TTX. Ca2+ spikes were observed
      in 50% of the cases. 5. Single action potentials were followed by fast
      hyperpolarizations having mean duration of 92.7 +/- 6.0 ms and amplitude of 13.3
      +/- 1.0 mV. In 62.5% of the cells repetitive firing of action potentials was
      followed by delayed, slow hyperpolarizations (duration 3.8 +/- 0.5 s), which were
      diminished by the K+ channel blocker 4-aminopyridine and in Ca+2-free high-Mg2+
      medium. These results indicate that the prolonged after-spike hyperpolarizations
      were due to opening of Ca(2+)-induced K+ channels. 6. Electrical stimulation of
      nerve fiber tracts evoked fast excitatory synaptic potentials that were blocked
      by the nicotinic receptor antagonist hexamethonium (0.2 mM). Exogenous
      acetylcholine elicited depolarizations that were also blocked by hexamethonium.
      Nerve stimulation at frequencies of 0.1 Hz or higher caused strong facilitation
      of the synaptic potentials. Stimulation at 10-20 Hz did not evoke slow synaptic
      potentials.

PMID- 8747199
TI  - Mechanism of block by ZD 7288 of the hyperpolarization-activated inward
      rectifying current in guinea pig substantia nigra neurons in vitro.
AB  - 1. The effects of the novel bradycardic agent 4-(N-ethyl-N-phenylamino)-1,2
      dimethyl-6-(methylamino) pyrimidinium chloride (ZD 7288) (Zeneca) were
      investigated on the hyperpolarization-activated cationic current (Ih) in guinea
      pig substantia nigra pars compacta neurons in vitro, using a single
      microelectrode current-clamp/voltage-clamp technique. 2. Under current-clamp
      conditions, injection of large negative current pulses (0.1-0.5 nA, 400 ms)
      evoked a slow depolarizing "sag" in the electrotonic potential due to activation
      of the slow inward (anomalous) rectifier. In voltage-clamp recordings,
      hyperpolarizing voltage steps from a holding potential of -60 mV (close to
      resting potential) elicited slow inward current relaxations with kinetic
      properties similar to those seen for other neuronal Ihs. 3. ZD 7288 (10-100
      microM) produced a consistent abolition of the electrotonic potential sag with no
      effect on membrane potential or spike properties. Under voltage clamp, Ih
      amplitude was clearly reduced in a time- and concentration-dependent manner
      (apparent half-maximum blocking concentration = 2 microM); full block of Ih was
      typically achieved after 10-15 min of exposure to 50 microM ZD 7288, with no
      significant recovery observed after 1 h of washing. 4. A similar (although more
      rapid) block of Ih was seen after application of 3-5 mM Cs+ (partially reversible
      after 30 min of washing). 5. Partial block of Ih by 10 microM ZD 7288 was
      accompanied by a reduction in the maximum amplitude of the Ih activation curve, a
      small negative shift in its position on the voltage axis, and a linearization of
      the steady-state current-voltage relationship. The estimated Ih reversal
      potential, however, remained unaffected. 6. In 10 microM ZD 7288, the time course
      of Ih activation and deactivation was significantly slowed (within the range of 
      70 to -120 mV for the activation time constant and -70 to -90 mV for the
      inactivation time constant). 7. Blockade of Ih by ZD 7288 or Cs+ was independent
      of prior Ih activation (i.e., non-use dependent). 8. Intracellular loading with
      ZD 7288 also abolished the sag in the electrotonic voltage response and Ih
      relaxations, suggesting an intracellular site of action. By contrast,
      intracellular Cs+ had no effect on Ih properties. 9. Block of Ih by ZD 7288 (but
      not Cs+) was relieved by prolonged cell hyperpolarization, manifested as a slowly
      developing (half-time approximately 20 s) inward current at a holding potential
      of -100 mV. 10. We propose that ZD 7288, when applied externally, may behave as a
      "lipophilic" quaternary cation, capable of passing into the cell interior to
      block Ih channels in their closed state; this compound may thus prove a useful
      research tool, in place of Cs+, for studying the properties and significance of
      Ih currents in controlling neuronal function.

PMID- 8747200
TI  - Structural basis of cortical synchronization. I. Three types of interhemispheric
      coupling.
AB  - 1. Single-unit and multiunit activities were recorded at the area 17-18 border of
      each cortical hemisphere in paralyzed cats anesthetized with nitrous oxide
      supplemented with halothane. Cross-correlation histograms (CCHs) were computed
      between 86 pairs of single units and 99 pairs of multiunit activities. Visually
      evoked peaks in the CCHs were removed by subtracting the shift predictor. 2.
      Three types of CCH peaks were observed: T peaks with narrow widths (4-28 ms), C
      peaks with intermediate widths (30-100 ms), and H peaks with large widths (100
      1,000 ms). Oscillatory coupling was observed rarely. This tripartite distribution
      of CCH peaks is similar to that reported in an earlier study on the temporal
      coupling between areas 17 and 18. Different types of peaks occurred in isolation
      or in combination. Combination of different peak types was more often observed in
      multiunit recordings. 3. CCH peaks of all types were usually centered, meaning
      that units in opposite hemispheres tend to synchronize their discharges. 4. T
      peaks were observed almost exclusively for units with overlapping receptive
      fields and preferentially for units with similar optimal orientations. No
      dependence on receptive field position or optimal orientation was observed for
      the encounter rate of C and H peaks. 5. A new method, called the peristimulus
      CCH, was developed to study the time course of the temporal coupling. This showed
      that H peaks can occur during visual stimulation and that their time course
      follows that of the visual responses of the coupled neurons. 6. Using one single
      bar or two simultaneously presented light bars as stimuli, we studied the effect
      of visual stimulation on the strength of H coupling. This showed that H coupling
      observed under stimulation with a single moving light bar can be completely
      abolished, with little change in visual responses, when the stimulus is changed
      to two noncoherently moving bars. This was related to a strong decrease of the H
      peaks in the autocorrelograms. 7. These results demonstrate that T, C, and H
      peaks constitute, together with high-frequency oscillations, universal forms of
      temporal coupling between neurons located in different cortical areas. The
      following paper reports on the effects of cortical lesions on the encounter rate
      and strength of these different types of coupling.

PMID- 8747202
TI  - Computation of long-distance propagation of impulses elicited by Poisson-process
      stimulation.
AB  - 1. The purpose of this work was to determine whether computed temporally coded
      axonal information generated by Poisson process stimulation were modified during
      long-distance propagation, as originally suggested by S. A. George. Propagated
      impulses were computed with the use of the Hodgkin-Huxley equations and cable
      theory to simulate excitation and current spread in 100-microns-diam unmyelinated
      axons, whose total length was 8.1 cm (25 lambda) or 101.4 cm (312.5 lambda).
      Differential equations were solved numerically, with the use of trapezoidal
      integration over small, constant electrotonic and temporal steps (0.125 lambda
      and 1.0 microsecond, respectively). 2. Using dual-pulse stimulation, we confirmed
      that for interstimulus intervals between 5 and 11 ms, the conduction velocity of
      the second of a short-interval pair of impulses was slower than that of the first
      impulse. Further, with sufficiently long propagation distance, the second
      impulse's conduction velocity increased steadily and eventually approached that
      of the first impulse. This effect caused a spatially varying interspike interval:
      as propagation proceeded, the interspike interval increased and eventually
      approached stabilization. 3. With Poisson stimulation, the peak amplitude of
      propagating action potentials varied with interspike interval durations between 5
      and 11 ms. Such amplitude attenuation was caused by the incomplete relaxation of
      parameters n (macroscopic K-conductance activation) and h (macroscopic Na
      conductance inactivation) during the interspike period. 4. The stochastic
      properties of the impulse train became less Poisson-like with propagation
      distance. In cases of propagation over 99.4 cm, the impulse trains developed
      marked periodicities in Interevent Interval Distribution and Expectation Density
      function because of the axially modulated transformation of interspike intervals.
      5. Despite these changes in impulse train parameters, the arithmetic value of the
      mean interspike interval did not change as a function of propagation distance.
      This work showed that in theory, whereas the pattern of Poisson-like impulse
      codes was modified during long-distance propagation, their mean rate was
      conserved.

PMID- 8747201
TI  - Structural basis of cortical synchronization. II. Effects of cortical lesions.
AB  - 1. To understand the structural basis of the different types of interhemispheric
      synchronizations described in the preceding paper, we made sections of the corpus
      callosum and lesions of extrastriate cortex. We measured the effects of such
      operations on the frequency of encounter, width and strength of T, C, and H peaks
      in cross-correlation histograms computed from single-unit and multiunit
      recordings from areas 17-18 of opposite cortical hemispheres in the cat. 2.
      Sectioning of the corpus callosum led to a complete abolition of T and C
      couplings and a strong reduction of encounter rate and strength of H coupling. A
      section limited to the posterior half of the corpus callosum abolished T and C
      couplings completely. This suggests that T and C couplings are mediated by the
      direct reciprocal connections between visual cortical areas circulating through
      the posterior part of the corpus callosum. 3. The encounter rate of H peaks
      depended on the extent of the callosal cut. Larger lesions gave a more pronounced
      reduction of the number of H peaks. From this observation we conclude that H
      peaks are at least partially mediated by polysynaptic pathways involving widely
      distributed cortical regions. 4. Extensive lesions of extrastriate cortex were
      made by aspiration of the gray matter or injections of ibotenic acid. These
      lesions removed the direct inputs from cortical areas sending ipsilateral as well
      as contralateral inputs to the area 17-18 border region. Encounter rate and
      coupling strength of C and H peaks were decreased, whereas little effect was
      observed on T peaks. 5. These results demonstrate that all types of
      interhemispheric synchronization are mediated by corticocortical connections and
      that T and C peaks are generated by reciprocal connections between areas 17 and
      18 of each hemisphere. Feedback connections play a role in mediating or
      facilitating the C and H types of interhemispheric synchronization.

PMID- 8747203
TI  - Extranuclear dendrites of locus coeruleus neurons: activation by glutamate and
      modulation of activity by alpha adrenoceptors.
AB  - 1. Locus coeruleus (LC) neurons were recorded extracellularly and intracellularly
      in rat brain slices. Effects of glutamate applied to the area of distal
      extranuclear LC dendrites, and of alpha-2 adrenoceptors applied in the bath, were
      determined on activity of these cells. 2. Glutamate applied to the area of distal
      dendrites potently activated LC neurons. These responses were not blocked by
      either 1 microM tetrodotoxin or 2 mM Co(2+)-10 mM Mg2+. This indicates that
      glutamate acting directly on distal dendrites can potently activate LC neurons.
      3. Bath application of the alpha-2 adrenoceptor antagonists yohimbine (1 microM)
      or idazoxan (1 microM) significantly increased responses of LC neurons evoked by
      dendritic glutamate application. These antagonist treatments also transiently
      decreased, and then increased, spontaneous discharge activity in LC neurons. 4.
      Alterations in spontaneous and glutamate-evoked activities after blockade of
      alpha-2 adrenoreceptors were not observed in LC neurons of reserpinized rats.
      This indicates that the altered LC activity and responsiveness to glutamate
      following alpha-2 antagonist treatment in nonreserpinized slices are mediated via
      blockade of effects of endogenously released noradrenaline. 5. The alpha-1
      antagonist prazosin (1 microM) caused a small but reliable decrease in the
      spontaneous firing rate of LC neurons. After prazosin pretreatment, alpha-2
      antagonists did not evoke the expected delayed increase in LC spontaneous firing
      and response to glutamate application. These results indicate that activation of
      alpha-1 adrenoceptors may contribute to the delayed increase in excitability of
      LC neurons after alpha-2 antagonist administration. The possible roles of alpha-1
      and alpha-2 adrenoreceptors in regulation of spontaneous discharge rate and
      glutamate-evoked responses in LC neurons are discussed.

PMID- 8747204
TI  - Hebbian induction of LTP in visual cortex: perforated patch-clamp study in
      cultured neurons.
AB  - 1. To see whether presynaptic activation paired with postsynaptic depolarization
      is necessary for the induction of long-term potentiation (LTP) in visual cortex
      or whether an activation of postsynaptic receptors in conjunction with
      depolarization is sufficient, we carried out perforated patch-clamp recordings
      with nystatin from cultured cortical neurons of rats. 2. Recorded neurons were
      monosynaptically activated either by electrical stimulation of an adjacent neuron
      or by direct activation of glutamate on "hot spots" of dendrites through
      iontophoresis or pressure ejection. In experiments in which cultured neurons were
      stained immunocytochemically with antibody against synaptophysin after
      electrophysiological recordings, hot spots were found to correspond to probable
      synaptic sites. 3. Excitatory postsynaptic currents (EPSCs) evoked by test
      stimulation applied to the adjacent neuron at 0.1 Hz were recorded at a holding
      potential of -60 or -70 mV for 5-10 min after an establishment of the whole cell
      recording configuration. Then, stimulation was paired with postsynaptic
      depolarization (0 mV for 200 ms) at 1 Hz for 30 or 60 s. LTP of EPSCs was induced
      in 7 of the 15 cells from which stable recordings were obtained for 18-30 min
      after pairing. 4. When postsynaptic depolarization was paired with direct
      glutamate application in the absence of presynaptic stimulation in 12 cells, only
      1 showed LTP. Postsynaptic depolarization alone did not induce LTP in any of the
      six cells tested. Also, presynaptic stimulation alone did not induce LTP in any
      of the five cells tested. 5. These results suggest that the concurrent activation
      of presynaptic elements with postsynaptic depolarization is necessary for the
      induction of LTP in visual cortex.

PMID- 8747205
TI  - Inputs from the ipsilateral and contralateral vestibular apparatus to
      behaviorally characterized abducens neurons in rhesus monkeys.
AB  - 1. We made extracellular recordings from neurons in the abducens nuclei of alert
      rhesus monkeys during electrical stimulation of the vestibular labyrinths with
      brief current pulses and during smooth pursuit, steady fixation, and the
      vestibuloocular reflex (VOR) evoked by passive head turns. The responses to
      electrical stimuli were compared with quantitative measures of the sensitivity of
      each neuron to eye position and eye velocity. We also compared the strengths of
      the vestibular inputs from the labyrinths ipsilateral and contralateral to the
      side of recording. 2. Abducens neurons showed transient excitation after a
      current pulse was applied to the contralateral labyrinth and transient inhibition
      after stimulation of the ipsilateral labyrinth. The latency of excitation had a
      mean value of 1.7 ms and a median value of 1.5 ms. Latency was unimodally
      distributed with little variation among neurons. Neurons with large responses
      showed a second phase of excitation that started 2.5 ms after the stimulus. 3. In
      two of three monkeys, the excitatory responses of abducens neurons to electrical
      stimulation of the contralateral labyrinth were approximately 3 times as large as
      their inhibitory responses to stimulation of the ipsilateral labyrinth. The
      difference in response size was not observed in the third monkey. The asymmetry
      in the size of the electrically evoked inputs from the two labyrinths was
      associated with a smaller asymmetry in responses of abducens neurons during the
      VOR evoked by passive head turns. The increase in firing rate during head
      rotation away from the side of the recording was almost always larger than the
      decrease in firing rate during head rotation toward the side of the recording. 4.
      The size of the neuronal response to electrical stimulation was correlated with
      the magnitude of the change in discharge rate during eye movements. Single or
      multiple regression of measures of response amplitude against eye position
      threshold, sensitivity to eye position, sensitivity to eye velocity, and baseline
      discharge rate yielded correlation coefficients that ranged from 0.26 to 0.92 in
      different monkeys. The existence of positive correlations is consistent with a
      role of the intrinsic properties of abducens neurons in determining recruitment
      order. However, the existence of large amounts of variability within most of the
      samples suggests that the recruitment order of abducens neurons also depends on
      the discharge properties of the afferents to each abducens neuron.

PMID- 8747206
TI  - Light responses from one type of ON-OFF amacrine cells in the rabbit retina.
AB  - 1. The light responses from one type of ON-OFF amacrine cell were recorded
      intracellularly in the superfused rabbit retina under various conditions of light
      adaptation. These recordings were obtained from cells located in a central area.
      5-7 mm inferior and directly below the optic nerve head. 2. ON-OFF amacrine cells
      responded to the initiation and termination of light stimuli with transient
      depolarizations. Their receptive fields were approximately 0.8-1 mm diam and did
      not exhibit antagonistic center-and-surround organization. 3. The cells received
      rod input because they responded to very dim scotopic stimuli. With prolonged
      dark adaptation, the cells became more sensitive to the initiation than
      termination of the stimulus, because the ON component of the light response had a
      lower threshold than the OFF component. 4. The cells continued to respond to test
      flashes when the retina was adapted to a background illumination of rod
      saturating intensity. Thus ON-OFF amacrine cells also receive cone input. Under
      these photopic conditions, a secondary afterpotential was observed following the
      OFF component. Its characteristics were different from those of the rod
      aftereffect reported in other retinal cells of the rabbit because its latency and
      amplitude changed with increasing stimulus intensity. 5. Intracellular injections
      of horseradish peroxidase showed that the recordings were obtained from a class
      of ON-OFF amacrine cells whose wide-field, unistratified dendrites were
      rigorously confined to the middle of the inner plexiform layer or stratum 3. 6.
      The conspicuous rod and cone inputs into a class of amacrine cells that are
      connected neither to rod bipolars nor to All amacrine cells strongly support the
      idea that in the rabbit the rod pathway uses cone bipolars as interneurons to
      distribute scotopic signals to ganglion and cone-driven amacrine cells.

PMID- 8747207
TI  - Neural responses to simple simulated echoes in the auditory brain stem of the
      unanesthetized rabbit.
AB  - 1. In most natural environments, sound waves from a single source will reach a
      listener through both direct and reflected paths. Sound traveling the direct path
      arrives first, and determines the perceived location of the source despite the
      presence of reflections from many different locations. This phenomenon is called
      the "law of the first wavefront" or "precedence effect." The time at which the
      reflection is first perceived as a separately localizable sound defines the end
      of the precedence window and is called "echo threshold." The precedence effect
      represents an important property of the auditory system, the neural basis for
      which has only recently begun to be examined. Here we report the responses of
      single neurons in the inferior colliculus (IC) and superior olivary complex (SOC)
      of the unanesthetized rabbit to a sound and its simulated reflection. 2. Stimuli
      were pairs of monaural or binaural clicks delivered through earphones. The
      leading click, or conditioner, simulated a direct sound, and the lagging click,
      or probe, simulated a reflection. Interaural time differences (ITDs) were
      introduced in the binaural conditioners and probes to adjust their simulated
      locations. The probe was always set at the neuron's best ITD, whereas the
      conditioner was set at the neuron's best ITD or its worst ITD. To measure the
      time course of the effects of the conditioner on the probe, we examined the
      response to the probe as a function of the conditioner-probe interval (CPI). 3.
      When IC neurons were tested with conditioners and probes set at the neuron's best
      ITD, the response to the probe as a function of CPI had one of two forms: early
      low or early-high. In early-low neurons the response to the probe was initially
      suppressed but recovered monotonically at longer CPIs. Early-high neurons showed
      a nonmonotonic recovery pattern. In these neurons the maximal suppression did not
      occur at the shortest CPIs, but rather after a period of less suppression. Beyond
      this point, recovery was similar to that of early-low neurons. The presence of
      early-high neurons meant that the overall population was never entirely
      suppressed, even at short CPIs. Taken as a whole. CPIs for 50% recovery of the
      response to the probe among neurons ranged from 1 to 64 ms with a median of
      approximately 6 ms. 4. The above results are consistent with the time course of
      the precedence effect for the following reasons. 1) The lack of complete
      suppression at any CPI is compatible with behavioral results that show the
      presence of a probe can be detected even at short CPIs when it is not separately
      localizable. 2) At a CPI corresponding to echo threshold for human listeners
      (approximately 4 ms CPI) there was a considerable response to the probe,
      consistent with it being heard as a separately localizable sound at this CPI. 3)
      Full recovery for all neurons required a period much longer than that associated
      with the precedence effect. This is consistent with the relatively long time
      required for conditioners and probes to be heard with equal loudness. 5.
      Conditioners with either the best ITD or worst ITD were used to determine the
      effect of ITD on the response to the probe. The relative amounts of suppression
      caused by the two ITDs varied among neurons. Some neurons were suppressed about
      equally by both types of conditioners, others were suppressed more by a
      conditioner with the best ITD, and still others by a conditioner with the worst
      ITD. Because the best ITD and worst ITD presumably activate different pathways,
      these results suggest that different neurons receive a different balance of
      inhibition from different sources. 6. The recovery functions of neurons not
      sensitive to ITDs were similar to those of ITD-sensitive, neurons. This suggests
      that the time course of suppression may be common among different IC populations.
      7. We also studied neurons in the SOC. Although many showed binaural
      interactions, none were sensitive to ITDs. Thus the response of this population
      may not be

PMID- 8747208
TI  - Effect of cycloheximide and mRNA synthesis inhibition on death of trophically
      deprived ciliary ganglion neurons in culture.
AB  - 1. The relationship between cycloheximide (CHX) and RNA synthesis inhibitors on
      trophic-deprived neuronal survival was studied with the use of primary cultures
      of stage (St) 34 chick ciliary ganglion (CG) neurons, to analyze the biological
      process of neuronal death caused by trophic factor withdrawal. Tissue culture
      conditions were refined by characterizing the additional medium components
      required to obtain 100% survival, for at least 1 wk, in the presence of an eye
      extract [choroid, ciliary body, iris, and pigment epithelium (CIPE)] as a trophic
      support for the neurons. Highly enriched neuronal cultures almost devoid of
      nonneuronal cells were used. 2. The time at which trophically deprived neurons
      cannot be rescued by the addition of trophic support, "commitment point," was
      established to be between 11 and 17 h after trophic deprivation. 3. CHX, an
      inhibitor of protein translation, reduced 3H-leucine incorporation by 90-95%, at
      a concentration of 10-100 micrograms/ml. The effect of the RNA transcription
      blockers actinomycin D (Act-D), alpha-amanitin, and 5.6 dichlorobenzimidazole
      riboside (DRB) on 3H-uridine incorporation into macromolecules was evaluated.
      Total RNA synthesis was inhibited by 10-25% by alpha-amanitin, whereas Act-D and
      DRB inhibited 80-97.5% of the 3H-uridine incorporation. 4. The effect of short-
      and long-term incubation with CHX on neuronal survival was analyzed. Continuous
      application of CHX promoted survival for 2-3 days, but thereafter neurons died
      regardless of whether CIPE was present or absent. Application of CHX for 6 h from
      the onset of the culture was enough to delay the commitment point up to 24 h
      after plating, and the addition of CIPE at this time maintained survival and
      promoted differentiation of CHX treated neurons. 5. The RNA transcription
      blockers Act-D, alpha-amanitin, and DRB were applied to both trophically deprived
      and trophically supported neurons, and the survival of each was evaluated.
      Neither drug was effective in supporting the survival of trophically deprived
      neurons in culture, and in most cases neurons even when cultured with CIPE died
      within 1-2 days in the presence of either drug. 6. Experiments using both CHX and
      mRNA synthesis blockers were performed to determine the effect of blocking mRNA
      transcription in trophically deprived neurons rescued by CHX. The addition of
      mRNA synthesis inhibitors precluded the effect of CHX on neuronal survival. 7.
      The effect of CHX (20 micrograms/ml) on RNA and protein synthesis was studied by
      measuring the incorporation of radiolabeled metabolic precursors (3H-leucine or
      3H-uridine) into macromolecules. A 95% reduction in the protein synthesis was
      observed after 1 h of application of the drug, and by 24 h, 3H-leucine
      incorporation was reduced to 15-20% of the control values. Wash out of CHX after
      6 h of incubation produced a recovery of protein synthesis up to 50% of control
      values 18 h later. CHX did not affect the synthesis of RNA for up to 12 h;
      however, it impaired the ability of the cell to take up metabolic precursors. 8.
      In conclusion, the present results support the hypothesis that the CHX effect on
      neuronal survival is due to its ability to induce the expression of survival or
      protective genes rather than to block the expression of killer proteins. This
      view is supported by 1) the 24-h delay of the commitment point following the
      short-term application of CHX, 2) the impaired ability of CHX to rescue trophic
      deprived neurons by the addition of mRNA synthesis blockers, and 3) the fact that
      neuronal survival caused by trophic factors like CIPE, is blocked by blocking RNA
      transcription.

PMID- 8747209
TI  - Brain stem integration of vocalization: role of the nucleus retroambigualis.
AB  - 1. The descending pathways that mediate the periaqueductal gray (PAG)-evoked
      coordination of respiratory, laryngeal, and orofacial activity for vocalization
      have yet to be delineated. Two hypotheses have been offered. One theory is that
      this activity is mediated by a diffuse descending projection to parvocellular
      reticular interneurons, adjacent to the relevant laryngeal and orofacial
      motoneuronal pools. The second hypothesis is that the motor activity for
      vocalization is integrated via a projection from the PAG to a caudal medullary
      column of neurons, the nucleus retroambigualis (NRA). These hypotheses were
      tested with the use of a series of medullary transections combined with PAG
      stimulation. Transections that eliminated, in a series of caudal-to-rostral
      steps, the NRA, also eliminated the PAG-evoked cricothyroid and most of the
      thyroarytenoid laryngeal motor activity. These results indicate that the final
      common pathway for much of the laryngeal activity in PAG-evoked vocalization
      includes un initial synapse in the caudal medulla, presumably in the NRA. 2. The
      electromyographic changes evoked by microinjection of D,L-homocysteic acid (DLH)
      in the NRA of the unanesthetized, precollicular decerebrate cat were analyzed in
      order to delineate the NRA contribution to the coordinated respiratory,
      laryngeal, and oral muscle changes in vocalization. A total of 415 DLH injection
      sites were located at or caudal to the level of the obex. Vocalization was evoked
      at 46 of these sites, which were all confined to a restricted region of the
      ventrolateral medulla 1-3 mm caudal to the obex. This region corresponded to the
      rostral half of the NRA and the immediately adjacent medullary tegmentum. 3. In
      all experiments evidence was obtained that variable muscle activation, rather
      than functional and integrated muscle patterns, was represented within the NRA.
      Vocalization evoked by DLH microinjection in the NRA was usually associated with
      excitation of the cricothyroid, thyroarytenoid, external oblique, internal
      oblique, internal intercostal, and diaphragm muscles that occurred in a different
      manner from site to site. That is, injection at sites separated by 0.3-0.5 mm
      evoked quite different responses. 4. NRA-evoked vocalization was compared with
      PAG-evoked vocalization using small injections (1.5-4.5 nl) into each region. As
      well, larger microinjections (15-120 nl) into NRA were made for comparison with
      previous results from the PAG using similar doses. Within the PAG, stereotyped
      and relatively "fixed" patterns of muscle activity are represented, whereas
      within the NRA there was no representation of specific muscle patterns, but
      rather a partial topographic separation of "premotor neurons" regulating
      different muscles. Correspondingly, stereotyped vocalizations were never evoked
      from the NRA. Further, most NRA-evoked vocalizations were unusual in quality and
      would not be identified generally as feline. 5. Evidence was obtained for a
      separation of pathways from the PAG regulating sound production and orofacial
      modulation of that sound. In contrast to the results from the PAG, excitation of
      NRA neurons rarely evoked activity in the oral muscles (genioglossus or anterior
      belly of digastric) or orofacial modulation of sound production. 6. Our finding
      suggests that the NRA serves as an important substrate for the generation of
      respiratory pressure and larynges adduction, which are two essential aspects of
      not only vocalization but also several behaviors involving Valsava maneuvers such
      as coughing, vomiting, and defecation.

PMID- 8747210
TI  - Transduction and adaptation in spider slit sense organ mechanoreceptors.
AB  - 1. Mechanoreceptor neurons in spider (Cupiennlus salei) slit sense organ were
      examined by intracellular current- and voltageclarry recordings. Steps and
      pseudorandomly modulated displacement stimuli were delivered to the
      mechanosensitive cuticular slits. The resulting responses were used to determine
      the response dynamics and signal-to-noise ratio (SNR) of mechanoelectrical
      transduction. 2. Neurons were separated into two groups that, in terms of their
      afferent discharges, displayed different adaptations to displacement stimuli.
      Both responded at the onset of the step but then adapted fully, either
      immediately or within 10-200 ms. Voltage-clamp recordings showed only small
      differences in the receptor currents of the two groups. 3. Displacement of the
      slit caused a large inward current that decayed in seconds to a steady level of
      approximately 10-25% of the initial transient. When adapted to a steady
      displacement, the neurons responded to superimposed displacements in the same
      direction with additional transient currents, whose decay could be fitted by two
      exponentials with time constants of approximately 10 and 100 ms. In contrast,
      displacement in the opposite direction caused small "outward" currents without
      obvious adaptation. This behavior persisted with increasing background
      displacements, suggesting a shift in the displacement-response curve along the
      displacement axis. 4. White noise stimulation supported the step data and
      confirmed that the receptor's sensitivity was independent of mean slit membrane
      displacement. When the relative displacement of the stimulus (i.e., strain) was
      held constant at different maintained backgrounds, the SNR of the neurons
      remained fairly constant at approximately 2-10 over the frequency range from 4 to
      450 Hz. The receptor current frequency responses showed high-pass
      characteristics, with a two- to sevenfold enhancement of the response amplitude
      and a phase lag relative to the stimulus of 90 degrees at 300 Hz. Low coherence
      values in the frequency range of 0.5-125 Hz were explained by nonlinear
      adaptation. 5. We conclude that, by rapidly adapting to the mean displacement of
      the slit membrane, slit organ mechanoreceptor neurons maintain a high sensitivity
      and SNR that allow the detection of small and rapid changes in cuticular strain.

PMID- 8747211
TI  - Outward currents in heart motor neurons of the medicinal leech.
AB  - 1. Outward currents were studied in isolation in heart motor neurons in the
      medicinal leech, using the single-electrode voltage-clamp technique. The currents
      were divided into four distinct types on the basis of their time and voltage
      characteristics and sensitivity to external Ca2+ concentration. 2. The four types
      were a fast transient current, IKA; a slow transient current. IK1; a
      noninactivating current, IK2, all measured in a bathing solution in which Co2+
      was substituted for Ca2+; and a calcium-sensitive current. IK1Cal which was
      revealed in a bathing solution containing normal levels of Ca2+. 3. The outward
      currents in heart motor neurons studied in different ganglia possessed
      differences of quality. For example, heart motor neurons from ganglia 3 or 4 had
      significantly less IK2 and IK1 than neurons recorded from more posterior ganglia.
      Heart motor neurons from ganglion 3 often had little or no IK1. Soma input
      resistance, electrotonic length, and soma capacitance measured in heart motor
      neurons from both anterior and posterior ganglia exhibited no significant
      differences. 4. IKA started to activate near -45 mV with half-maximal activation
      at about -20 mV and was fully inactivated by 0 mV: IK1 started to activate near 
      45 mV with half-maximal activation at about -10 mV and was not fully inactivated
      by 0 mV; IK2 started to activate near -50 mV; IK1Cal started to activate near -35
      mV. The time constant of removal of inactivation for IKA was 25 ms, measured at 
      80 mV, and that for IK1 was 380 ms, measured at -40 mV. 5. Tetraethylammonium
      acetate (TEA) allowed to diffuse from the inside of the recording microelectrode
      effectively blocked IKA, IK1, and IK2. Bath-applied TEA (25 mM) acted similarly
      but was less effective, particularly at blocking Ik2. Bath-applied 4
      aminopyridine effectively blocked the transient currents IKA and IK1. A reversal
      potential of -65 mV was found for the outward currents, corresponding to a mix of
      IK1 and IK2.

PMID- 8747212
TI  - Nonlinear models of the first synapse in the light-adapted fly retina.
AB  - 1. Randomly modulated light stimuli were used to characterize the nonlinear
      dynamic properties of the synapse between photoreceptors and large monopolar
      neurons (LMC) in the fly retina. Membrane potential fluctuations produced by
      constant variance contrast stimuli were recorded at eight different levels of
      background light intensity. 2. Representation of the photoreceptor-LMC input
      output data in the form of traditional characteristic curves indicated that
      synaptic gain was reduced by light adaptation. However, this representation did
      not include the time-dependent properties of the synaptic function, which are
      known to be nonlinear. Therefore nonlinear systems analysis was used to
      characterize the synapse. 3. The responses of photoreceptors and LMCs to random
      light fluctuations were characterized by second-order Volterra series, with
      kernel estimation by the parallel cascade method. Photoreceptor responses were
      approximately linear, but LMC responses were clearly nonlinear. 4. Synaptic input
      output relationships were measured by passing the light stimuli to LMCs through
      the measured photoreceptor characteristics to obtain an estimate of the synaptic
      input. The resulting nonlinear synaptic functions were well characterized by
      second-order Volterra series. They could not be modeled by a linear-nonlinear
      linear cascade but were better approximated by a nonlinear-linear-nonlinear
      cascade. 5. These results support two possible structural models of the synapse,
      the first having two parallel paths for signal flow between the photoreceptor and
      LMC, and the second having two distinct nonlinear operations, occurring before
      and after chemical transmission. 6. The two models were cach used to calculate
      the synaptic gain to a brief change in photoreceptor membrane potential. Both
      models predicted that synaptic gain is reduced by light adaptation.

PMID- 8747213
TI  - Transfer characteristics of lateral geniculate nucleus X neurons in the cat:
      effects of spatial frequency and contrast.
AB  - 1. The dependence of signal transfer in the lateral geniculate nucleus (LGN) on
      stimulus spatial frequency and contrast was investigated by comparing responses
      of individual X cells with their direct retinal inputs. 2. We used extracellular
      single-cell recording methods to isolate action potentials (LGN) and S potentials
      (SPs) from individual neurons in layers A and A1 of anesthetized and paralyzed
      cats. The stimuli were drifting sinusoidal gratings that were presented at each
      neuron's preferred orientation. The effects of stimulus spatial frequency and
      contrast on retinogeniculate signal transfer were determined by comparing the
      amplitude of the fundamental Fourier responses measured for a cell's action
      potentials (LGN) and its retinal input (SP) and calculating the transfer ratio
      (LGN amplitude/SP amplitude) for each stimulus condition. 3. In all units, the
      LGN response amplitude was lower than that of its retinal input regardless of
      stimulus spatial frequency. The mean transfer ratio measured at the peak spatial
      frequency for individual units was 0.56 +/- 0.03 (SE). For the majority of X LGN
      neurons, however, the efficiency of signal transfer varied considerably with
      stimulus spatial frequency. The average transfer ratio increased monotonically
      from 0.08 cycle/deg to near the high cutoff spatial frequency. 4. The effects of
      stimulus contrast on geniculate signal transfer were far more complex than
      previously reported and varied substantially between individual neurons. At low
      stimulus contrasts (< 10%), where all units exhibited linear response
      characteristics, only one third of our sample showed a monotonic decrease in
      transfer ratio with increasing stimulus contrast. The remaining two thirds either
      exhibited proportionately greater signal transfer for higher stimulus contrasts,
      or signal transfer remained relatively unchanged with increasing stimulus
      contrasts. When stimulus contrasts exceeded 10%, where response amplitude began
      to saturate, the transfer ratio was relatively constant in all units and
      independent of stimulus contrast. 5. Our results demonstrate that signal transfer
      from retina to visual cortex is regulated by LGN neurons in a stimulus-dependent
      manner, which appears to reflect the complex interactions between local membrane
      mechanisms and extraretinal inputs.

PMID- 8747214
TI  - Transfer characteristics of X LGN neurons in cats reared with early discordant
      binocular vision.
AB  - 1. The effects of early discordant binocular vision on the functional development
      of the cat lateral geniculate nucleus (LGN) were investigated by quantitatively
      comparing responses of individual LGN neurons with their direct retinal inputs.
      2. Unilateral convergent strabismus (esotropia) was surgically induced in 11
      kittens at the age of 3 wk. After the animals had reached 9 mo of age,
      extracellular microelectrode recordings were made from individual X LGN units in
      lamina A and A1 of anesthetized and paralyzed cats. Responses were measured for
      drifting sinusoidal gratings. Within-unit comparisons of LGN action potentials
      (LGN output) and S potentials (retinal input) were performed to determine the
      nature of signal transfer in the units driven by the deviating (N = 42) or
      nondeviating eyes (N = 29) of strabismic cats. The results were compared with
      similar data (N = 29) obtained from nine normal control cats. 3. The spatial
      resolution of many individual LGN units in strabismic cats was abnormally reduced
      relative to their retinal inputs. These differences were more pronounced in units
      that received inputs from the nasal retina of the contralateral eye. The
      resolution loss was closely associated with a dramatic decrease in the strength
      of the receptive field center mechanism of LGN units relative to their retinal
      inputs. Moreover, the efficiency of signal transfer for high-spatial-frequency
      stimuli, determined by the transfer ratio (response amplitude of LGN action
      potentials/amplitude of S potentials), was significantly lower in strabismic cats
      compared with normal controls. 4. In strabismic cats, contrast thresholds for the
      action potentials of individual LGN units were significantly higher than those
      determined for the S potentials. In normal cats, the input-output differences in
      contrast threshold were negligible. The observed contrast sensitivity loss was
      more pronounced for high-spatial-frequency stimuli. 5. The speed of signal
      transfer was significantly decreased in the LGNs of strabismic animals. The
      visual response latencies of many, but not all, X LGN cells in the strabismic
      cats were abnormally long when compared with those in normal control units,
      whereas SP latencies were virtually the same for strabismic and normal cats.
      Abnormal latencies were prevalent in units that exhibited contrast threshold
      deficits, and were more severe among the units receiving input from the
      contralateral nasal retina. 6. The deficits in strabismic cats were found in the
      LGN units innervated by the deviating and nondeviating eyes. However, for the
      majority of response measures, the units innervated by the deviating eyes showed
      notably larger deficits. 7. We conclude that the fidelity of signal transfer from
      the retina to the LGN is significantly reduced in cats reared with discordant
      binocular visual experience. Thus the adverse effects of early strabismus are not
      confined, at least in cats, to the visual cortex.

PMID- 8747215
TI  - Vestibular and visual climbing fiber signals evoked in the uvula-nodulus of the
      rabbit cerebellum by natural stimulation.
AB  - 1. The cerebellar uvula-nodulus receives vestibular projections from primary and
      secondary vestibular afferents as well as vestibularly related climbing fibers.
      It also receives visually related information from climbing fiber pathways. In
      this experiment we investigated how this information is mapped onto the uvula
      nodulus. We studied the specificity, dynamics, and topographic distribution of
      climbing fiber responses (CFRs), simple spike responses, and mossy fiber terminal
      responses evoked by vestibular and optokinetic stimulation in rabbits
      anesthetized with alpha-chloralose. 2. Vestibularly evoked CFRs were found in the
      ventral uvula and nodulus. These responses were evoked during static roll tilt of
      the rabbit about a longitudinal axis and by sinusoidal oscillation about the
      longitudinal axis. Purely static responses were attributed to stimulation of the
      utricular otolith by the linear acceleration of gravity. CFRs that lacked a
      static component were attributed to activation of the semicircular canals. 3.
      Using a "null technique" we showed that the canal-sensitive CFRs were caused by
      stimulation of the anterior or posterior semicircular canals. Of the CFRs
      classified as canal related, 96% could be attributed to stimulation of the
      vertical semicircular canals. 4. Increases in CFRs were correlated with decreases
      in simple spike responses in half the Purkinje cells from which we recorded.
      These climbing-fiber-induced pauses in simple spikes occurred during spontaneous
      climbing fiber discharge as well as during climbing fiber discharge evoked by
      vestibular stimulation. The duration of this pause was inversely proportional to
      the spontaneous level of simple spikes before the occurrence of a CFR. In the
      other half of the recorded population of Purkinje cells, vestibularly driven CFRs
      did not alter the simple spike responses. 5. Vestibularly and visually mediated
      CFRs were topographically represented on the surface of the uvula-nodulus. CFRs
      driven by ipsilateral otolithic inputs were distributed over the entire
      mediolateral surface of the uvula-nodulus. CFRs driven by the ipsilateral
      posterior semicircular canal were distributed in a sagittal strip approximately
      1.5 mm wide, extending laterally from the midline of the nodulus. CFRs driven
      exclusively by horizontal, posterior-->anterior optokinetic stimulation of the
      ipsilateral eye were distributed in a sagittal strip approximately 0.5 mm wide
      located 0.5-1.0 mm from the midline and restricted to the ventral nodulus. CFRs
      driven by the ipsilateral anterior semicircular canal were found in a sagittal
      strip approximately 1.0 mm wide extending 1.0-2.0 mm from the midline. 6. The
      sagittal, topographically arrayed climbing fiber strips effectively map a
      mediolateral gradient of possible postural responses based on vestibular and
      optokinetic information.

PMID- 8747216
TI  - Magnesium-dependent block of the light-activated and trp-dependent conductance in
      Drosophila photoreceptors.
AB  - 1. The effect of Mg2+ on the light-sensitive conductance in Drosophila
      photoreceptors was examined with the use of whole cell voltage-clamp recordings
      from dissociated ommatidia. In wild type (WT) photoreceptors, at resting
      potential (-70 mV). Mgo2+ reduces response amplitude by up to approximately 4
      fold in the presence of normal (1.5 mM) Cao2+ and by up to 20-fold in the absence
      of Cao2+. The Mg2+ concentration required for 50% maximum block (K1/2) was
      approximately 1 mM with 1.5 mM Cao2+ and approximately 280 microM in Ca(2+)-free
      Ringer. 2. The Mg2+ block was largely relieved in photoreceptors of the transient
      receptor potential mutant (trp): the maximum block being only approximately
      twofold with a K1/2 of approximately 4 mM in both Ca(2+)-free and 1.5 mM Cao2+.
      3. The Mg2+ block in WT, but not in trp, was strongly voltage dependent, being
      relieved by both hyperpolarization and depolarization. The Mg2+ block in WT also
      resulted in slower response kinetics because of the associated decrease in Ca2+
      influx. 4. Noise analysis indicates that, with normal Ca(zero)2+, the Mg2+ block
      in WT is associated with a approximately 10-fold reduction in effective single
      channel conductance al resting potential. 5. The results support the hypothesis
      that the trp gene encodes a subunit of a light-sensitive channel, which is
      required for sensitivity to block by Mg2+. The concentration and voltage
      dependence of the Mg2+ block suggest it plays an important physiological role in
      determining the gain, kinetics, and signal-to-noise of transduction.

PMID- 8747217
TI  - Calcium-activated release of nitric oxide potentiates excitatory synaptic
      potentials in immature rat sympathetic preganglionic neurons.
AB  - 1. Whole cell patch recordings were made from sympathetic preganglionic neurons
      (SPNs), the majority of which contain brain nitric oxide synthase (bNOS), in
      transverse spinal cord slices of 12- to 16-day-old rats. 2. Repetitive discharge
      of SPNs induced by a train of depolarizing current pulses (40 Hz. 10 s) was
      followed by a long-lasting increase (140 +/- 22%, mean +/- SD) of the amplitude
      of excitatory postsynaptic potentials (EPSPs) evoked by stimulation of lateral
      funiculus in 50 of 75 SPNs. 3. In slices pretreated with the nitric oxide
      synthase inhibitors, NG-monomethyl-L-arginine (L-NMA: 100 microM) or Nw-nitro-L
      arginine (L-NARG; 30 microM) or with bovine hemoglobin (100 microM), repetitive
      discharge of SPNs was not followed by a significant increase of EPSPs. 4.
      Superfusing the slices with L-arginine (L-Arg, 300 microM) but not D-Arg
      reversibly increased the EPSPs by an average of 140 +/- 19%. 5. Inclusion of the
      Ca2+ chelator 1.2-bis(2-aminophenoxy)- ethane-N,N,N',N'-tetraacetic acid (BAPTA,
      1 mM) in the patch electrodes resulted in no significant increase of EPSPs after
      repetitive discharge in all cells studied. 6. It is concluded that during
      repetitive discharge of SPNs, Ca2+ influx via voltage-gated channels activates
      bNOS, resulting in a release of nitric oxide and potentiation of EPSPs.

PMID- 8747218
TI  - Halothane-induced synaptic depression at both in vivo and in vitro reconstructed
      synapses between identified Lymnaea neurons.
AB  - 1. In the present study we tested the ability of the general anesthetic,
      halothane, to affect synaptic transmission at in vivo and in vitro reconstructed
      peptidergic synapses between identified neurons of Lymnaea stagnalis. 2. An
      identified respiratory interneuron, visceral dorsal 4 (VD4), innervates a number
      of postsynaptic cells in the central ring ganglia of Lymnaea. Because VD4 has
      previously been shown to exhibit immunoreactivity for FMRFamide-related peptides,
      it was hypothesized that these peptides may be utilized by VD4 during synaptic
      transmission. In the intact, isolated CNS of Lymnaea, we have identified novel
      connections between VD4 and the pedal A (PeA) cells. We demonstrate that VD4
      makes inhibitory connections with the PeA neurons, in particular PeA4, and that
      these synaptic responses are mimicked by exogenous application of FMRFamide. 3.
      The synaptic transmission between VD4 and the PeA cells in an intact, isolated
      CNS preparation was completely blocked in 2%, but not 1% halothanc.
      Interestingly, the postsynaptic responses (PeA) to exogenous FMRFamide were
      maintained in the presence of both 1 and 2% halothane. 4. To determine the
      specificity of the observed responses and to determine the precise synaptic site
      of anesthetic action, we reconstructed the VD4/PeA synapses in vitro. After
      isolation from their respective ganglia, both cell types extended processes and
      established neuritic contact. We demonstrated that not only did the presynaptic
      neuron reestablish the appropriate inhibitory synapses with the PeA neurons, but
      that the PeA cells also maintained their responsiveness to exogenous FMRFamide.
      5. Superfusion of the in vitro synaptically connected VD4 and PeA cells with 2%
      halothane completely abolished the synaptic transmission between these cells.
      However, even higher concentrations of 4% halothane failed to block the
      responsiveness of the PeA neurons to exogenous FMRFamide. Moreover, both 1 and 2%
      halothane enhanced the duration of the postsynaptic response to exogenously
      applied FMRFamide. These data suggest that the halothane-induced depression of
      synaptic transmission most likely occurred at the presynaptic level. 6. This
      study provides the first direct evidence that peptidergic transmission in the
      nervous system may also be susceptible to the actions of general anesthetics. In
      addition, we utilized a novel approach of in vitro reconstructed synapses for
      studying the effects of general anesthetics on monosynaptic transmission in the
      absence of other synaptic influences.

PMID- 8747219
TI  - Widespread mechanosensory activation of the serotonergic system of the medicinal
      leech.
AB  - The serotonergic system of the medicinal leech comprises a small number of
      iterated, identified neurons, of which the Retzius (Rz) neurons are major
      components. Activity in pressure mechanosensory (P) cells sufficient to elicit
      locomotory and defensive behaviors also excites Rz neurons. We characterized the
      interactions between P and Rz neurons within the ganglion and at different
      distances along the nerve cord. 2. Within a ganglion 1) P cells excited both Rz
      neurons, electrically close to the site of electrical coupling between the Rz
      neurons; 2) each of the four P cells had similar effects on the Rz neurons; and
      3) homologous contralateral P cells shared interneuronal pathways. These data
      show that P cells provide nearly identical bilateral information onto Rz neurons.
      3. Along the nerve cord 1) every P cell excited Rz neurons in ganglia anterior
      and posterior to the site of stimulation; 2) the signal was carried the entire
      length of the nerve cord along interneuronal pathways with similar overall (but
      regionally different) conduction velocities in the two directions; 3) the
      amplitude of the Rz responses was smaller as the distance to the activated P cell
      increased; 4) the rate of change of the amplitude along the cord was larger when
      the signal traveled from front-to-back than in the opposite direction. 4. These
      data shows that mechanosensory input from any segment could excite Rz neurons
      along the cord, in proportion to the intensity of the stimulus.

PMID- 8747220
TI  - Axotomy induces a transient and localized elevation of the free intracellular
      calcium concentration to the millimolar range.
AB  - 1. Axonal transection triggers a cascade of pathological processes that
      frequently lead to the degeneration of the injured neuron. It is generally
      believed that the degenerative process is triggered by an overwhelming influx of
      calcium through the cut end of the axon. 2. Theoretical considerations and
      indirect observations suggest that axotomy is followed by an increase in the free
      intracellular calcium concentration ([Ca2+]i) to the millimolar level. In
      contrast, only relatively modest and transient elevation in [Ca2+]i to the
      micromolar level was revealed by recent fura-2 studies. 3. In the current study
      we used the low-affinity Ca2+ indicator mag-fura-2 to reexamine the
      spatiotemporal distribution pattern of Ca2+ after axotomy and to map the free
      intracellular Mg2+ concentration gradients. 4. We report that axotomy elevates
      [Ca2+]i well beyond the "physiological" range of calcium concentrations, to
      levels > 1 mM near the tip of the cut axon and to hundreds of micromolars along
      the axon further away from the cut end. Nevertheless, [Ca2+]i recovers to the
      control levels within 2-3 min after the resealing of the cut end. 5. A comparison
      of the behavior of fura-2 and mag-fura-2 in the cytosol of the axotomized neurons
      reveals that the determination of [Ca2+]i by fura-2 largely underestimates the
      actual intracellular Ca2+ concentrations. 6. Experiments in which one branch of a
      bifurcated axon was transected revealed that the elevation in [Ca2+]i is confined
      to the transected axonal branch and does not spread beyond the bifurcation point.
      7. After axotomy, the intracellular Mg2+ concentration equilibrates rapidly with
      the external concentration and then recovers at a rate somewhat slower than that
      of [Ca2+]i. 8. To the best of our knowledge, this study is the first direct
      demonstration that axotomy elevates [Ca2+]i to the millimolar range and that
      neurons are able to recover from these extreme calcium concentrations.

PMID- 8747221
TI  - Motor and somatosensory corticostriatal projection magnifications in the squirrel
      monkey.
AB  - 1. Motor and somatosensory cortex project massively to the primate striatal
      matrix, terminating in distributed sets of overlapping projection zones
      (matrisomes) within the putamen. To study this system quantitatively, we have
      developed a computer-assisted estimation of the changes in magnification that
      occur as motor and somatosensory cortical body representations are projected onto
      the putamen. 2. Cortical and striatal body maps were assessed in squirrel monkeys
      by injecting anterograde tract tracers into electrophysiologically identified
      body-part representations in cortical areas 4, 3a, 3b, and 1. Relative projection
      magnification was defined as the ratio of the cortical injection site volume to
      the striatal projection site volume. 3. Magnification comparisons indicate that
      the tracers wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) and
      35S-methionine have similar sensitivities. 4. The relative proportions of body
      part representations in the striatal maps were not significantly different from
      those in cortical maps. Both had large representations of hand, foot, and mouth,
      and smaller representations of trunk. 5. The relative magnification of the motor
      cortex projection to the striatum was roughly twice as large as those of
      projections from individual somatosensory areas. 6. These findings suggest that,
      in the sensorimotor striatum, motor and somatosensory inputs may undergo
      different proportions of local processing at the borders of their distribution
      zones (striosomes and matrisomes).

PMID- 8747222
TI  - Patterns of synaptic activity in forward and feedback pathways within rat visual
      cortex.
AB  - 1. The laminar and temporal distribution of synaptic activity supplied by forward
      and feedback connections between different areas of rat visual cortex was
      determined with the use of current source density (CSD) analysis in in vitro
      slices. In forward connections, synaptic potentials were evoked by electrically
      stimulating area 17 and recording in the extrastriate area LM (lateromedial),
      that ranks at the second hierarchical level, one step above primary visual
      cortex. For activating feedback connections, the location of stimulating and
      recording electrodes was reversed. 2. The synaptic interactions in reciprocal
      intracortical circuits are excitatory, and they are mediated through glutamate
      receptors that are blocked by kynurenic acid. 3. Forward connections from area 17
      to area LM provide input to all layers including a strong input to layer 4. In
      contrast, feedback input to layer 4 is weak and is mainly directed to superficial
      and deep layers. This laminar distribution closely resembles that seen
      anatomically. 4. Both forward and feedback connections evoke distinct temporal
      patterns of synaptic activation in different layers. Although onset and peak
      latencies are slightly shorter in the forward than in the feedback pathway, the
      difference is not statistically significant. 5. The spatiotemporal distribution
      of synaptic activation by forward connections resembles the pattern evoked by
      geniculocortical inputs. Feedback connections show greater similarities to long
      range connections within area 17, although they are not identical. Our results
      support the notion derived from anatomic and in vivo physiological studies that
      forward and feedback pathways belong to functionally distinct cortical circuits.

PMID- 8747223
TI  - Neural computation of motion in the fly visual system: quadratic nonlinearity of
      responses induced by picrotoxin in the HS and CH cells.
AB  - 1. A computational model accounting for motion detection in the fly was examined
      by comparing responses in motion-sensitive horizontal system (HS) and centrifugal
      horizontal (CH) cells in the fly's lobula plate with a computer simulation
      implemented on a motion detector of the correlation type, the Reichardt detector.
      First-order (linear) and second-order (quadratic nonlinear) Wiener kernels from
      intracellularly recorded responses to moving patterns were computed by cross
      correlating with the time-dependent position of the stimulus, and were used to
      characterize response to motion in those cells. 2. When the fly was stimulated
      with moving vertical stripes with a spatial wavelength of 5-40 degrees, the HS
      and CH cells showed basically a biphasic first-order kernel, having an initial
      depolarization that was followed by hyperpolarization. The linear model matched
      well with the actual response, with a mean square error of 27% at best,
      indicating that the linear component comprises a major part of responses in these
      cells. The second-order nonlinearity was insignificant. When stimulated at a
      spatial wavelength of 2.5 degrees, the first-order kernel showed a significant
      decrease in amplitude, and was initially hyperpolarized; the second-order kernel
      was, on the other hand, well defined, having two hyperpolarizing valleys on the
      diagonal with two off-diagonal peaks. 3. The blockage of inhibitory interactions
      in the visual system by application of 10-4 M picrotoxin, however, evoked a
      nonlinear response that could be decomposed into the sum of the first-order
      (linear) and second-order (quadratic nonlinear) terms with a mean square error of
      30-50%. The first-order term, comprising 10-20% of the picrotoxin-evoked
      response, is characterized by a differentiating first-order kernel. It thus codes
      the velocity of motion. The second-order term, comprising 30-40% of the response,
      is defined by a second-order kernel with two depolarizing peaks on the diagonal
      and two off-diagonal hyperpolarizing valleys, suggesting that the nonlinear
      component represents the power of motion. 4. Responses in the Reichardt detector,
      consisting of two mirror-image subunits with spatiotemporal low-pass filters
      followed by a multiplication stage, were computer simulated and then analyzed by
      the Wiener kernel method. The simulated responses were linearly related to the
      pattern velocity (with a mean square error of 13% for the linear model) and
      matched well with the observed responses in the HS and CH cells. After the
      multiplication stage, the linear component comprised 15-25% and the quadratic
      nonlinear component comprised 60-70% of the simulated response, which was similar
      to the picrotoxin-induced response in the HS cells. The quadratic nonlinear
      components were balanced between the right and left sides, and could be
      eliminated completely by their contralateral counterpart via a subtraction
      process. On the other hand, the linear component on one side was the mirror image
      of that on the other side, as expected from the kernel configurations. 5. These
      results suggest that responses to motion in the HS and CH cells depend on the
      multiplication process in which both the velocity and power components of motion
      are computed, and that a putative subtraction process selectively eliminates the
      nonlinear components but amplifies the linear component. The nonlinear component
      is directionally insensitive because of its quadratic non-linearity. Therefore
      the subtraction process allows the subsequent cells integrating motion (such as
      the HS cells) to tune the direction of motion more sharply.

PMID- 8747224
TI  - Representation of a species-specific vocalization in the primary auditory cortex
      of the common marmoset: temporal and spectral characteristics.
AB  - 1. The temporal and spectral characteristics of neural representations of a
      behaviorally important species-specific vocalization were studied in neuronal
      populations of the primary auditory cortex (A1) of barbiturate-anesthetized adult
      common marmosets (Callithrix jacchus), using both natural and synthetic
      vocalizations. The natural vocalizations used in electrophysiological experiments
      were recorded from the animals under study or from their conspecifics. These
      calls were frequently produced in vocal exchanges between members of our marmoset
      colony and are part of the well-defined and highly stereotyped vocal repertoire
      of this species. 2. The spectrotemporal discharge pattern of spatially
      distributed neuron populations in cortical field A1 was found to be correlated
      with the spectrotemporal acoustic pattern of a complex natural vocalization.
      However, the A1 discharge pattern was not a faithful replication of the acoustic
      parameters of a vocalization stimulus, but had been transformed into a more
      abstract representation than that in the auditory periphery. 3. Subpopulations of
      A1 neurons were found to respond selectively to natural vocalizations as compared
      with synthetic variations that had the same spectral but different temporal
      characteristics. A subpopulation responding selectively to a given monkey's call
      shared some but not all of its neuronal memberships with other individual-call
      specific neuronal subpopulations. 4. In the time domain, responses of individual
      A1 units were phase-locked to the envelope of a portion of a complex
      vocalization, which was centered around a unit's characteristic frequency (CF).
      As a whole, discharges of A1 neuronal populations were phase-locked to discrete
      stimulus events but not to their rapidly changing spectral contents. The
      consequence was a reduction in temporal complexity and an increase in cross
      population response synchronization. 5. In the frequency domain, major features
      of the stimulus spectrum were reflected in rate-CF profiles. The spectral
      features of a natural call were equally or more strongly represented by a
      subpopulation of A1 neurons that responded selectively to that call as compared
      with the entire responding A1 population. 6. Neuronal responses to a complex call
      were distributed very widely across cortical field A1. At the same time, the
      responses evoked by a vocalization scattered in discrete cortical patches were
      strongly synchronized to stimulus events and to each other. As a result, at any
      given time during the course of a vocalization, a coherent representation of the
      integrated spectrotemporal characteristics of a particular vocalization was
      present in a specific neuronal population. 7. These results suggest that the
      representation of behaviorally important and spectrotemporally complex species
      specific vocalizations in A1 is 1) temporally integrated and 2) spectrally
      distributed in nature, and that the representation is carried by spatially
      dispersed and synchronized cortical cell assemblies that correspond to each
      individual's vocalizations in a specific and abstracted way.

PMID- 8747225
TI  - Adaptation of carotid chemoreceptors to step increases in PaCO2 in anesthetized
      cats.
AB  - 1. The rate of change sensitivity of some carotid chemoreceptors to within-breath
      changes in PaCO2 would suggest that the half-life of adaptation of these
      receptors to a step increase is shorter than the 5-10 s previously reported. 2.
      In six anesthetized cats, step increases in PaCO2 (10 in each cat) were produced
      by injection of CO2 into the inspired gas during high-frequency jet ventilation.
      Chemoreceptor discharge was recorded from single-fiber preparations of the
      divided carotid sinus nerve, and the changes in PaCO2 were followed with the use
      of an in vivo pH electrode. 3. The adaptation half-lives were 0.3, 0.8, 1.2, 1.3,
      1.6, and 8.6 s. The physiological significance of these findings in terms of
      respiratory control and the mechanism of chemotransduction are discussed. The
      receptors with the shortest and longest half-lives showed corresponding
      differences in response to sine-wave oscillations in PaCO2. 4. In a further group
      of five cats, chemoreceptor responses to step increases in PaCO2 were tested
      before and during infusion of KCl to produce a mean arterial [K-] of 6.8 +/- 0.2
      (SE) mM. Under these conditions the hyperkalemia caused no further increase in
      discharge. 5. We conclude that adaptation of the chemoreceptor response to
      increases in PaCO2 is much faster than previously reported and that this finding
      is consistent with observations of chemoreceptor responses to respiratory PaCO2
      oscillations.

PMID- 8747226
TI  - Simultaneous measurement of pH and membrane potential in rat dorsal vagal
      motoneurons during normoxia and hypoxia: a comparison in bicarbonate and HEPES
      buffers.
AB  - 1. The effects of oxygenated and hypoxic bicarbonate/CO2, 10 and 25 mM N-2
      hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered artificial
      cerebrospinal fluid (ACSF) have been studied in a rat brain slice preparation.
      Double-barreled pH-selective microelectrodes were used to measure intracellular
      pH (pHi) and membrane potential in dorsal vagal motoneurons (DVMs) and to measure
      extracellular pH (pHe) in the dorsal vagal motonucleus. 2. In bicarbonate ACSF,
      pHi averaged 7.24 +/- 0.05 (mean +/- SE, n = 21) and ranged from 6.86 to 7.79 pH
      units. pHe averaged 7.13 +/- 0.08 (n = 10). 3. On changing from oxygenated
      bicarbonate ACSF to either 10 or 25 mM HEPES ACSF, pHi decreased by 0.13-0.15
      units, and the membrane depolarized by 10-11 mV. pHe also decreased in 10 mM
      HEPES ACSF (pHe 6.89 +/- 0.02, n = 8) but not in 25 mM HEPES ACSF (pHe 7.15 +/-
      0.06, n = 3). In most neurons changes in pHi preceded changes in membrane
      potential. 4. In bicarbonate ACSF and in 25 mM HEPES ACSF, there was a
      significant linear relationship between prehypoxic pHi and the direction and
      amplitude of the hypoxia-induced membrane potential change (either an
      hyperpolarization or a depolarization). 5. In 10 mM HEPES ACSF, hypoxia always
      induced a depolarization; there was no correlation between prehypoxic pHi and the
      membrane potential response. 6. In bicarbonate ACSF and in 10 and 25 mM HEPES
      ACSF, hypoxia resulted in intracellular and extracellular acidification. However,
      the extracellular acidification in hypoxic 10 mM HEPES buffer was most pronounced
      (pH 6.40 +/- 0.11, n = 8), reflecting a preexisting extracellular acidification
      in oxygenated 10 mM HEPES buffer. 7. Various hypotheses that could give rise to a
      relationship between changes in membrane potential and pH are discussed;
      arguments are presented in favor of the concept that modulation of ion channels
      by either pHi or pHe, or both, is responsible for the observed correlations.

PMID- 8747227
TI  - Semicircular canal contributions to the three-dimensional vestibuloocular reflex:
      a model-based approach.
AB  - 1. We studied the contribution of the individual semicircular canals to the
      generation of horizontal and torsional eye movements in cynomolgus monkeys. Eye
      movements were elicited by sinusoidal rotation about a vertical (gravitational)
      axis at 0.2 Hz with the animals tilted in various attitudes of static forward or
      backward pitch. The gains of the horizontal and torsional components of the
      vestibuloocular reflex (VOR) were measured for each tilt position. The gains as a
      function of tilt position were fit with sinusoidal functions, and spatial gains
      and phases were determined. After control responses were recorded, the
      semicircular canals were plugged, animals were allowed to adapt, and the test
      procedure was repeated. Animals were prepared with only the anterior and
      posterior canals intact [vertical canal (VC) animals], with only the lateral
      canals intact [lateral canal (LC) animal], and with only one anterior and the
      contralateral posterior canals intact [right anterior and left posterior canal
      (RALP) animals; left anterior and right posterior canal (LARP) animals]. 2. In
      normal animals, the gain of the horizontal (yaw axis) velocity of the
      compensatory eye movements decreased as they were pitched forward or backward,
      and a torsional velocity appeared, reversing phase at the peak of the horizontal
      gain. After the anterior and posterior canals were plugged (LC animal), the
      horizontal component was reduced when the animal was tilted backward; the gain
      was zero with about -60 degrees of backward tilt. The spatial phase of the
      torsional component had the same characteristics. This is consistent with the
      fact that both responses were produced by the lateral canals, which from our
      results are tilted between 28 and 39 degrees above the horizontal stereotaxic
      plane. 3. After both lateral canals were plugged (VC animals), horizontal
      velocity was reduced in the upright position but increased as the animals were
      pitched backward relative to the axis of rotation. Torsional velocities, which
      were zero in the upright position in the normal animal, were now 180 degrees out
      of phase with the horizontal velocity. The peak values of the horizontal and
      torsional components were significantly shifted from the normal data and were
      closely aligned with each other, reaching peak values at approximately -56
      degrees pitched back (-53 degrees horizontal, -58 degrees torsional). The same
      was true for the LARP and RALP animals; the peak values were at -59 degrees
      pitched back (-55 degrees horizontal, -62 degrees torsional). Likewise, in the LC
      animal the peak yaw and roll gains occurred at about the same angle of forward
      tilt, 35 degrees (30 degrees horizontal, 39 degrees torsional). Thus, in each
      case, the canal plugging had transformed the VOR from a compensatory to a
      direction-fixed response with regard to the head. Therefore there was no
      adaptation of the response planes of the individual canals after plugging. 4. The
      data were compared with eye velocity predictions of a model based on the
      geometric organization of the canals and their relation to a head coordinate
      frame. The model used the normal to the canal planes to form a nonorthogonal
      coordinate basis for representing eye velocity. An analysis of variance was used
      to define the goodness of fit of model predictions to the data. Model predictions
      and experimental data agreed closely for both normal animals and for the animals
      with canal lesions. Moreover, if horizontal and roll components from the LC and
      VC animals were combined, the summation overlay the response of the normal
      monkeys and the predictions of the model. In addition, a combination of the RALP
      and LARP animals predicted the response of the lateral-canal-plugged (VC)
      animals. 5. When operated animals were tested in light, the gains, peak values,
      and spatial phases of horizontal and roll eye velocity returned to the
      preoperative values, regardless of the type of surgery performed. This indicates
      that vision compensated for the lack o

PMID- 8747228
TI  - Identified octopaminergic neurons provide an arousal mechanism in the locust
      brain.
AB  - 1. Habituation is the declining responsiveness of a neural circuit (or behavior)
      to repetitive stimulation. Dishabituation (or arousal) can be brought about by
      the sudden presentation of an additional, novel stimulus. A clear example of
      arousal in the locust is provided by the visual system: the habituated response
      of the descending contralateral movement detector (DCMD) interneuron to
      repetitive visual stimuli can be dishabituated by a variety of other visual and
      tactile stimuli. 2. Application of octopamine to the locust brain and optic lobes
      dishabituates the DCMD in a manner similar to the effect of visual and tactile
      stimulation. 3. The locust CNS contains two pairs of octopamine-immunoreactive
      cells, the protocerebral medulla 4 (PM4) neurons, that could potentially mediate
      this dishabituation effect; PM4 neurons arborize in the optic lobe, they contain
      octopamine, and they respond to the same visual and tactile stimuli that
      dishabituate the DCMD. 4. To investigate whether PM4 activity dishabituates the
      DCMD, we recorded intracellularly from one of the PM4 neurons while recording
      extracellularly from the DCMD. When the PM4 neuron is injected with
      hyperpolarizing current to render it completely inactive, the DCMD exhibits its
      characteristic habituation to a moving visual stimulus. However, depolarizing the
      PM4 neuron, to produce action potentials at approximately 20 Hz, significantly
      increases the number of DCMD action potentials per stimulus. 5. The PM4 neurons
      may therefore play an important role in dishabituating the DCMD to novel stimuli.
      This effect is presumably mediated by PM4 neurons releasing endogenous octopamine
      within the optic lobe.

PMID- 8747229
TI  - Acute activation and inactivation of macaque frontal eye field with GABA-related
      drugs.
AB  - 1. This project tests the behavioral effects of reversible activation and
      inactivation of sites within the frontal eye field of rhesus monkeys with
      microinjections of the gamma-aminobutyric acid (GABA)-related drugs bicuculline
      and muscimol. 2. Muscimol injections impaired the monkeys' ability to make both
      visually and memory-guided saccades to targets at the center of the area
      represented by the injection site. The latencies of saccades to targets in
      regions flanking the injection were increased. For memory-guided saccades,
      saccades in the direction opposite to that represented by the injection site,
      were made with shorter latency than controls and often occurred before the
      movement cue. 3. Bicuculline injections produced irrepressible saccades
      equivalent to the saccade vector represented by the injection site, often in a
      staircase of several closely spaced movements. 4. Both substances decreased the
      accuracy of fixation of a central light. The distribution of points of fixation
      on different trials was diffuse, and the angle of gaze tended to deviate towards
      the side of the injection. 5. The results of these acute injections are similiar
      to those observed in the superior colliculus and are much more substantial than
      the effects observed in the long term after surgical removal of the frontal eye
      field. The results of this study promote a central role for the frontal eye field
      in the generation of all voluntary saccades and in the control of fixation.

PMID- 8747231
TI  - Pallidal neuron activity during sequential arm movements.
AB  - 1. We examined the activity of neurons in the globus pallidus (GP) while monkeys
      (n = 2) performed sequential pointing movements under two task conditions:
      visually guided (TRACK task) and remembered (REM task). 2. Almost two-thirds of
      the task-related neurons in GP (155/236) were considered task dependent because
      they displayed exclusive or enhanced (greater than +/- 50%) changes in activity
      for one of the two task conditions. 3. More than 65% of the task-dependent
      neurons were termed REM neurons because they either displayed changes in activity
      that occurred only during the REM task or displayed changes that were more
      pronounced (greater than +/- 50%) during the REM task than during the TRACK task.
      4. Nearly half of the REM neurons in GP displayed changes in activity that were
      limited to a single phase of the REM task (i.e., phase specific). Phase-specific
      neurons varied in the extent to which their activity depended on the particular
      sequence of movements performed. Some displayed a change in activity for all of
      the eight different movement sequences. Others displayed a change in activity
      during only one of the eight different sequences (i.e., phase and sequence
      specific). 5. We speculate that an ensemble of GP neurons with phase-specific
      responses could be used to encode the detailed spatio-temporal characteristics of
      a sequential movement. In this way, GP neurons would provide part of the neural
      substrate that solves the "serial order of motor behavior problem".

PMID- 8747230
TI  - Dopamine modulates the slow Ca(2+)-activated K+ current IAHP via cyclic AMP
      dependent protein kinase in hippocampal neurons.
AB  - 1. The effects of dopamine on the slow Ca(2+)-dependent K+ current (IAHP; AHP,
      afterhyperpolarization) and spike frequency adaptation were studied by whole cell
      voltage-clamp and sharp microelectrode current-clamp recordings in rat CA1
      pyramidal neurons in rat hippocampal slices. 2. Dopamine suppressed IAHP in a
      dose-dependent manner, under whole cell voltage-clamp conditions. Similarly,
      under current-clamp conditions, dopamine inhibited spike frequency adaptation and
      suppressed the slow afterhyperpolarization. 3. The effect of dopamine on IAHP was
      mimicked by a D1 receptor agonist and blocked by dopamine receptor antagonists
      only in a minority of the cells. 4. Dopamine suppressed IAHP after blocking or
      desensitizing the beta-adrenergic receptors and, hence, did not act by cross
      reacting with this receptor type. 5. The effects of dopamine on IAHP and spike
      frequency adaptation were suppressed by blocking the adenosine 3',5'-cyclic
      monophosphate (cAMP)-dependent kinase (PKA) with Rp-cAMPS and, hence, are
      probably mediated by the activation of this kinase. 6. We conclude that dopamine
      increases hippocampal neuron excitability, like other monoamine
      neurotransmitters, by suppressing IAHP and spike frequency adaptation, via cAMP
      and protein kinase A. The receptor type mediating this effect of dopamine remains
      to be defined.

PMID- 8747232
TI  - Block of cyclic nucleotide-gated channels in salamander olfactory receptor
      neurons by the guanylyl cyclase inhibitor LY83583.
AB  - 1. Using whole cell voltage-clamp recordings, the guanylyl cyclase inhibitor
      LY83583 [6-(phenylamino)-5,8-quinolinedione] is shown to act as a potent blocker
      of cyclic nucleotide-gated (CNG) channels in isolated olfactory receptor neurons
      (ORNs) of the tiger salamander. 2. Under our experimental conditions, onset of
      the blockade by LY83583 occurs on the time scale of seconds and is completely
      reversed upon wash-out of the drug. Dose-response curves reveal a Kd of 1.4
      microM (at -60 mV). Other data suggest that LY83583 acts within the CNG channel
      pore and that the channels must be in an activated state before the drug can
      exert its effect. 3. It appears that LY83583 can act on both CNG channels and
      soluble guanylyl cyclase (sGC) and that these two effects can be distinguished by
      their different recovery behaviors. The LY83583-induced blockade of CNG channels
      activated directly by guanosine 3',5' cyclic monophosphate (cGMP) is rapidly
      reversible (with a recovery time constant of approximately 3 s), whereas previous
      results have shown that no recovery is obtained during minute-long washing
      periods when the channels are activated indirectly through exogenous carbon
      monoxide application, which acts as a stimulator of sGC in ORNs. 4. LY83583
      appears to be a novel and useful agent in examining neural functions due to CNG
      channel responses.

PMID- 8747233
TI  - Long-term potentiation in hippocampal slices induced by temporary suppression of
      glycolysis.
AB  - 1. Temporary suppression of glycolysis by 2-deoxy-D-glucose (2-DG)-long enough to
      abolish CA1 population spikes (PSs) and reduce field excitatory postsynaptic
      potentials (EPSPs) by two-thirds-is followed by a sustained rebound of EPSPs and
      PSs (both up by 70-150%). 2. Post 2-DG long-term potentiation (2-DG-LTP) is
      prevented by block of N-methyl-D-aspartate (NMDA) receptors (NMDARs). Though 2-DG
      LTP is normally expressed by other receptors, in presence of picrotoxin 2-DG
      causes similar LTP of NMDAR-mediated EPSPs. 3. Stimulation at 1 s-1 fully
      depotentiates 2-DG-LTP. 4. Unlike tetanic LTP, 2-DG-LTP is not pathway-specific,
      is not occluded by a preceding tetanic LTP (or vice versa) and is insensitive to
      block of NO synthesis. 5. Hypoglycemic states may have long-lasting after-effects
      on cerebral synaptic function.

PMID- 8747234
TI  - Mechanical perturbation of cultured cortical neurons reveals a stretch-induced
      delayed depolarization.
AB  - 1. An in vitro cellular model of injury was used to elucidate mechanisms
      contributing to traumatic brain injury (TBI). Neonatal rat cortical neurons
      cultured on a flexible silastic membrane were stretched rapidly and reversibly by
      a 50-ms pulse of pressurized air. 2. Sublethal cell stretch depolarized neuronal
      resting membrane potential by approximately 10 mV but only if cells were
      incubated for 1 h after injury. Stretch-induced delayed depolarization (or SIDD)
      returned to baseline values within 24 h. 3. SIDD was dependent on the degree of
      cell stretch and required neuronal firing, calcium entry, and N-methyl-D
      aspartate receptor activation for its induction but not its maintainance. 4.
      Similarities between SIDD and TBI suggest that SIDD may play a role in brain
      injury.

PMID- 8747235
TI  - Benzolamide inhibits low-threshold calcium currents in hippocampal pyramidal
      neurons.
AB  - 1. Benzolamide is a poorly permeant sulfonamide inhibitor of the enzyme carbonic
      anhydrase. We studied the effect of benzolamide on low-threshold (LT) Ca currents
      in neonatal hippocampal CAl neurons. 2. In hippocampal slices, benzolamide (2-10
      microM) inhibited the LT current 30-75% in voltage-clamped CAl pyramidal cells (n
      = 6). In slices bathed in N-2-hydroxypiperazine-N'-2-ethane-sulfonic acid (HEPES)
      buffered Ringer, benzolamide also reduced the LT current, indicating that the
      action of the drug was not bicarbonate dependent. 3. Benzolamide inhibited LT Ca
      currents 20-75% in acutely dissociated CAl neurons in HEPES (n = 18): inhibition
      was 36 +/- 8% (mean +/- SE; n = 7) and 50 +/- 8% (n = 7) at 10 and 50 microM
      benzolamide, respectively. By contrast, high-threshold calcium currents recorded
      in CAl pyramidal cells (n = 18) and dorsal root ganglion neurons (n = 4) were
      virtually unaffected by benzolamide. 4. These results indicate that benzolamide
      inhibits LT Ca channels in central neurons and suggest caution in the use of this
      agent to inhibit extracellular carbonic anhydrase in excitable tissues.

PMID- 8747236
TI  - Nerve growth factor (NGF) acutely enhances high-voltage-activated calcium
      currents in molluscan neurons.
AB  - 1. Nerve growth factor (NGF) is a member of a family of molecules (the
      neurotrophins) that can regulate the survival and/or outgrowth of many vertebrate
      cells. NGF also induces outgrowth from Lymnaea neurons under experimental
      conditions. Recent studies have shown that the neurotrophins can also acutely
      modulate some physiological properties of adult neurons. Here we examined the
      actions of NGF on high-voltage-activated (HVA) Ca2+ currents in Lymnaea
      motoneurons. 2. NGF induced a dose-dependent and reversible increase in HVA Ca2+
      currents within 2 min. 3. The threshold dose of the NGF-induced enhancement of
      HVA Ca2+ currents ranged between 1 and 1,000 pg/ml. In the most sensitive cells,
      the response saturated at doses higher than 1 ng/ml. 4. The results indicate that
      neurotrophins acutely modulate voltage-gated Ca2+ currents in molluscan neurons
      through a high affinity signal transduction pathway. The data support the
      existence of neurotrophins in invertebrates. Moreover, this property of NGF may
      explain the neuromodulatory actions of neurotrophins observed in various
      preparations.

PMID- 8747237
TI  - Plasticity of the extensor group I pathway controlling the stance to swing
      transition in the cat.
AB  - 1. This study examines whether the efficacy of polysynaptic group I excitatory
      pathways to extensor motoneurons are modified after axotomy of a synergistic
      nerve. Previously, it has been shown that stimulation of extensor nerves at group
      I strength can extend the stance phase and delay swing. Stimulation of the
      lateral gastrocnemius and soleus (LG/S) nerve prolongs stance for the duration of
      the stimulus train, whereas stimulation of the medial gastrocnemius (MG) nerve
      moderately increases stance. Our hypothesis was that after axotomy of the LG/S
      nerve the efficacy of the MG group I input would increase. 2. This idea was
      tested in 10 adult cats that had their left LG/S nerves axotomized for 3-28 days.
      On the experimental day the cats were decerebrated and the left (experimental)
      and right (control) LG/S and MG nerves were stimulated during late stance as the
      animals were walking on a motorized treadmill. A significant increase in the
      efficacy of the left MG nerve occurred 5 days after axotomy of the LG/S nerve
      when compared with the control response. By contrast, the previously cut LG/S
      nerve showed a reduction in efficacy after 3 days compared with the control limb.
      3. Functionally, this plasticity may be an important mechanism by which the
      strength of the group I pathway is calibrated to different loads on the extensor
      muscles.

PMID- 8747238
TI  - 1995 Volvo Award in clinical sciences. Determinants of lumbar disc degeneration.
      A study relating lifetime exposures and magnetic resonance imaging findings in
      identical twins.
AB  - STUDY DESIGN: Retrospective cohort. OBJECTIVES: To investigate the effects of
      lifetime exposure to commonly suspected risk factors on disc degeneration using
      magnetic resonance imaging, and to estimate the effects of these suspected risk
      factors relative to age and familial aggregation, reflecting genetic and shared
      environmental influences. SUMMARY OF BACKGROUND DATA: Structural and biochemical
      changes associated with disc degeneration are suspected as the underlying
      conditions of many back-related symptoms. Little is known about the determinants
      of disc degeneration. METHODS: Based on lifetime discordance in suspected
      environmental risk factors for disc degeneration, 115 male identical twin pairs
      were selected. An in-depth interview was conducted of occupational and leisure
      time physical loading, driving, and smoking. Disc degeneration was evaluated
      using observational and digital magnetic resonance imaging assessment methods.
      RESULTS: Heavier lifetime occupational and leisure physical loading was
      associated with greater disc degeneration in the upper lumbar levels (P = 0.055 -
      0.001), whereas sedentary work was associated with lesser degeneration (P =
      0.006). These univariate associations did not reach statistical significance in
      the lower lumbar region. In multivariate analyses of the upper lumbar levels, the
      mean job code explained 7% of the variability in observational disc degeneration
      scores; the addition of age explained 16%, and familial aggregation improved the
      model such that 77% of the variability was explained. In the lower lumbar levels,
      leisure time physical loading entered the multivariate model, explaining 2% of
      the variability. Adding age explained 9%, and familial aggregation raised the
      variability in disc degeneration scores explained to 43%. CONCLUSIONS: The
      present study findings suggest that disc degeneration may be explained primarily
      by genetic influences and by unidentified factors, which may include complex,
      unpredictable interactions. The particular environmental factors studied, which
      have been among those most widely suspected of accelerating disc degeneration,
      had very modest effects.

PMID- 8747239
TI  - 1995 Volvo Award in clinical sciences. The diagnostic accuracy of magnetic
      resonance imaging, work perception, and psychosocial factors in identifying
      symptomatic disc herniations.
AB  - STUDY DESIGN: This was a prospective study of patients (study group) with
      symptomatic disc herniations and asymptomatic volunteers (control group) matched
      for age, sex, and work-related risk factors. OBJECTIVE: To determine the
      prevalence of disc herniation in a matched group of asymptomatic volunteers and
      to access the diagnostic accuracy of magnetic resonance imaging, work perception,
      and psychosocial factors in identifying symptomatic disc herniations. SUMMARY OF
      BACKGROUND DATA: Disc herniations have been reported to occur in 20-36% of
      asymptomatic volunteers. A valid comparison of asymptomatic individuals and
      patients with disc herniations has not been performed. METHODS: Forty-six
      patients with low back pain and sciatica severe enough to require a discectomy
      were compared with 46 age-, sex-, and risk factor-matched (heavy lifting,
      twisting and bending, vibration, and sedentary activity) asymptomatic volunteers.
      Both groups had a complete clinical and magnetic resonance imaging examination
      and completed a questionnaire to assess differences in the psychosocial and work
      perception profiles. The prevalence and the severity of morphologic alterations
      (disc herniation, disc degeneration, and neural compromise) was analyzed by tow
      independent radiologists in a blinded fashion. Differences between both groups
      regarding MRI findings, work perception (occupational mental stress, intensity of
      concentration, job satisfaction, and job-related resignation) and psychosocial
      factors (anxiety, depression, self-control, social support, and marital status)
      were compared using multivariate techniques. Stepwise discriminating analysis was
      used to identify the best discriminating variables within the magnetic resonance
      image, work perception, and psychosocial categories in terms of the diagnostic
      accuracy to predict group membership (study [pain] or control [no pain] group).
      RESULTS: Matched controls had significantly more risk factors than a group of
      normal individuals. The present study has presented evidence that an age-, gender
      , and occupational risk factors-matched group of asymptomatic patients shows a
      high incidence rate of disc herniations (76%). Although significantly less than
      the symptomatic group incidence of 96%, this represents a much higher prevalence
      rate than generally expected and reported in other studies of unmatched
      asymptomatic volunteers. Patients had more severe disc herniations (disc
      extrusions) than asymptomatic volunteers (35% vs. 13%). There was no significant
      differences regarding disc degeneration between both groups (96% vs. 85%). The
      only substantial morphologic difference between both groups was the presence of a
      neural compromise (83% vs. 22%), which was highly significant (P < 0.0001). There
      were significant differences between both groups regarding work perception
      (occupational mental stress, intensity of concentration, job satisfaction, and
      resignation; P < 0.027) and psychosocial factors (anxiety, depression, self
      control, marital status; P < 0.0001). The best single predictor of a group
      membership was the extent of neural compromise. A combination of this factor with
      occupational mental stress, depression, and marital status was the best
      predictive model. With this model, the false-negative rate (potential
      overtreatment of disc morphology) was reduced by more than half compared with
      morphologic factors (nerve root compression) alone (22% vs. 11%). CONCLUSIONS: In
      an age-, sex-, and risk factor-matched group of asymptomatic individuals, disc
      herniation had a substantially higher prevalence (76%) than previously reported
      in an unmatched group. Individuals with minor disc herniations (i.e., protrusion,
      contained discs) are at a very high risk that their magnetic resonance images are
      not a causal explanation of pain because a high rate of asymptomatic subjects
      (63%) had comparable morphologic findings. The only highly significant difference
      between the study group and control group regarding morphologic fi

PMID- 8747240
TI  - 1995 Volvo Award in basic sciences. The use of an osteoinductive growth factor
      for lumbar spinal fusion. Part I: Biology of spinal fusion.
AB  - STUDY DESIGN: The histology of lumbar intertransverse process spinal fusion was
      studied in an experimental model in rabbits. OBJECTIVES: To qualitatively and
      quantitatively analyze the sequential histology of spinal fusion using a
      previously validated animal model. SUMMARY OF BACKGROUND DATA: Few previous
      studies have described the sequential histology during the posterolateral spinal
      fusion healing process using autogenous bone, and a basic understanding of the
      biology of this repair process is lacking. METHODS: Fourteen adult New Zealand
      white rabbits underwent single-level posterolateral lumbar intertransverse
      process arthrodesis with autogenous iliac bone graft. Animals were killed 1-10
      weeks after surgery, and the fusion masses were analyzed histologically and
      quantitated using a semiautomated image analysis system. RESULTS: Three distinct
      phases of healing were identified (inflammatory, reparative, and remodeling) and
      occurred in sequence but in a delayed fashion in the central zone of the fusion
      mass compared with the outer transverse process zones. Membraneous bone
      formation, evident first at the ends of the fusion eminating from the
      decorticated transverse processes, was the predominant mechanism of healing. The
      central zone was somewhat different in that there was a period of endochondral
      bone formation during weeks 3 and 4 in this zone where cartilage formed and was
      converted to bone. Remodeling in the central zone had equilibrated with the
      transverse process zones by 10 weeks. CONCLUSIONS: Lumbar intertransverse process
      spinal fusion is a complex process from a spatial and temporal standpoint. When
      autogenous bone is used as the graft material, this process critically depends on
      a variety of factors from the decorticated host bone and exposed marrow. The
      persistence of a central cartilage zone may be related to some types of nonunions
      and deserves future investigation. This enhanced understanding of the biology of
      spinal fusion with autogenous bone graft will provide a foundation for optimizing
      the use of osteoinductive bone growth factors in this healing process.

PMID- 8747241
TI  - 1995 Volvo Award in basic sciences. The use of an osteoinductive growth factor
      for lumbar spinal fusion. Part II: Study of dose, carrier, and species.
AB  - STUDY DESIGN: Efficacy of a bovine-derived osteoinductive growth factor was
      studied in a rabbit model and in a nonhuman primate model of posterolateral
      lumbar spinal fusion. OBJECTIVES: To determine the minimum effective dose of
      growth factor and the influence of different carrier material on the outcome of
      intertransverse process lumbar fusion. SUMMARY OF BACKGROUND DATA: Bone
      morphogenetic proteins and related growth factors are becoming increasingly
      available in purified extract or genetically engineered forms and are capable of
      inducing new bone formation in vivo. Osteoinductive growth factors to enhance
      lumbar spinal infusion have not been well studied in models of posterolateral
      intertransverse process fusion. Because of the diminished potential of bone
      regeneration in primates (including humans) compared with phylogenetically lower
      animals, extrapolations regarding dose and efficacy cannot be made directly from
      results obtained in experiments performed on phylogenetically lower animals.
      Experiments on non-human primates are a critical step before attempting to use
      these growth factors on humans. METHODS. One hundred fifteen adult New Zealand
      white rabbits and 10 adult rhesus macaques underwent single level posterolateral
      intertransverse process lumbar spinal arthrodesis to evaluate different doses and
      carrier materials for a bovine-derived osteoinductive bone protein extract.
      Rabbit fusion masses were evaluated 5 weeks after arthrodesis by manual
      palpation, radiography, biomechanical testing, and light microscopy. Monkey
      fusion masses were evaluated 12 weeks after arthrodesis by radiography and light
      microscopy. RESULTS: Successful posterolateral intertransverse process spinal
      fusions were achieved in the rabbit models using an osteoinductive growth factor
      with three different carriers (autogenous iliac bone, demineralized allogeneic
      bone matrix, and natural coral). There was a dose-dependent response to the
      osteoinductive growth factor in the rabbit model, indicating that a threshold
      must be overcome before bone formation is induced. The methodology for biologic
      enhancement of spinal fusion developed in the rabbit model transferred
      successfully to the rhesus monkey, where the use of the osteoinductive growth
      factor with a demineralized bone matrix carrier resulted in spinal fusion in 12
      weeks. CONCLUSION: These experiments provide an essential building block in the
      understanding of the biology of spinal fusion and the use of osteoinductive
      growth factors to enhance a posterolateral intertransverse process spinal fusion.
      The achievement of posterolateral spinal fusion in the rhesus monkey using an
      osteoinductive growth factor is a significant step toward the biologic
      enhancement of spinal fusion in humans.

PMID- 8747242
TI  - Mechanoreceptors in intervertebral discs. Morphology, distribution, and
      neuropeptides.
AB  - STUDY DESIGN: The present study investigated the occurrence and morphology of
      mechanoreceptors in human and bovine intervertebral discs and longitudinal
      ligaments. OBJECTIVE: To determine the type and frequency of mechanoreceptors
      present in intervertebral discs and anterior longitudinal ligaments in two
      patient groups, those with low back pain and those with scoliosis. Bovine
      coccygeal discs were examined. SUMMARY OF BACKGROUND DATA: Nerves have been
      described in intervertebral tissues, but there is little information on the
      endings of these nerves and their receptors, stimulation of which can cause a
      nerve impulse. METHODS: The presence of mechanoreceptors were investigated by
      immunolocalization of nerves and neuropeptides. By examining sequential sections,
      the frequency of receptors was assessed. RESULTS: Immunoreactivity to neural
      antigens showed mechanoreceptors in the anulus fibrosus and longitudinal
      ligaments of bovine and human specimens. Their morphology resembled Pacinian
      corpuscles, Ruffini endings, and, most frequently, Golgi tendon organs. They were
      found in 50% of discs investigated from patients with low back pain and in 15% of
      those with scoliosis. CONCLUSIONS: Mechanoreceptors were found in the outer 2-3
      lamellae of the human intervertebral disc and anterior longitudinal ligament.
      Physiologic studies in other tissues indicate that these provide the individual
      with sensation of posture and movement, and in the case of Golgi tendon organs,
      of nociception. In addition to providing proprioception, mechanoreceptors are
      thought to have roles in maintaining muscle tone and reflexes. Their presence in
      the intervertebral disc and longitudinal ligament can have physiologic and
      clinical implications.

PMID- 8747243
TI  - Electromyographic response of the porcine multifidus musculature after nerve
      stimulation.
AB  - STUDY DESIGN: In this study, a porcine model was used to study whether a nerve
      reaction in the anulus fibrosus of a lumbar disc or in a facet joint capsule
      could cause a muscular response in the multifidus musculature. OBJECTIVES: To
      determine if there is an interrelationship between the intervertebral disc and
      facet joint innervation and the multifidus musculature as a possible pain
      mechanism. SUMMARY OF BACKGROUND DATA: The innervation of the anulus fibrosus of
      the intervertebral disc and the capsule of the facet joint is well described in
      the literature, although the functions of these nerves are poorly understood. An
      interrelationship between this innervation and the paraspinal musculature has not
      been previously described. METHODS: Fifteen adult pigs were used to measure the
      electromyographic response in the multifidus musculature to electrical
      stimulation of the lateral region of the disc anulus and the facet joint capsule
      in the L1-L2 motion segment. Motor unit action potentials were recorded using
      three sets of bipolar needle electrodes placed into the deepest fascicles of the
      multifidus, bilateral to the L2, L3, and L4 spinous processes. The effect of
      lidocaine injection into the facet joint and subperiosteal muscle detachment on
      the electromyographic response were studied. RESULTS: Stimulation of the disc
      anulus fibrosus induced reactions in the multifidus on multiple levels and on the
      contralateral side, whereas stimulation of the facet joint capsule induced
      reactions predominantly on the same side and segmental level as the stimulation.
      Introduction of lidocaine into the facet joint resulted in a significantly
      reduced electromyographic response to either stimulation, with the most drastic
      reduction seen when stimulating the facet joint capsule. Subperiosteal detachment
      of the paraspinal muscles prevented any muscular response. CONCLUSIONS:
      Stimulation of the disc and the facet joint capsule produced contractions in
      multifidus fascicles. The clinical implications are that there may be interactive
      responses between injured or diseased structures, i.e., disc or facet joints, and
      the paraspinal musculature. Activation of the multifidus muscles may have a
      stabilizing effect, constraining the motion of the lumbar spine. Longstanding
      muscular contraction may produce ischemic conditions and may be a potential
      source of pain.

PMID- 8747244
TI  - Phospholipase A2-induced electrophysiologic and histologic changes in rabbit
      dorsal lumbar spine tissues.
AB  - STUDY DESIGN: The present study was designed to characterize the effect of
      phospholipase A2 on the discharge of perispinal sensory nerves in the
      anesthetized New Zealand white rabbit. OBJECTIVES: To examine the effects of
      phospholipase A2 on the neural response of somatosensory neurons innervating the
      lumbar facet joint and surrounding tissues. SUMMARY OF BACKGROUND DATA: An
      irritating component of disc tissue may be phospholipase A2, which has been found
      at extraordinary high levels in herniated and painful discs. Phospholipase A2 has
      been shown to be inflammatory, but its effect on nerve response has never been
      shown. METHODS: Surgically isolated facet joint capsules from rabbits were
      investigated by means of electrophysiologic and histologic techniques.
      Phospholipase A2 was injected into the characterized nerve receptive field, and
      responses were evaluated over time with varying doses. RESULTS: The injection of
      phospholipase A2 into the nerve receptive fields produced neurotoxicity with a
      1500-U dose, sensitization of the nerves and recruitment of "silent units" with a
      750-U dose, and no electrophysiologic effect with a 400-U dose. The tissues
      injected with phospholipase A2 and control solutions were examined histologically
      using a hematoxylin and eosin staining technique. In all three doses, the
      inflammatory changes were observed as soon as 2 hours after the injections. In
      control subjects, no changes were observed. CONCLUSIONS: After phospholipase A2
      injection, the discharge rate of the units showed dose and time dependent
      patterns. Regardless of the different doses, histologic changes were observed as
      soon as 2 hours after the phospholipase A2 injections.

PMID- 8747245
TI  - Evaluation of rhBMP-2 with an OPLA carrier in a canine posterolateral (transverse
      process) spinal fusion model.
AB  - STUDY DESIGN: Posterolateral L4-L5 transverse process fusions were done on 14
      adult beagles. Six were implanted with recombinant human bone morphogenetic
      protein-2 carried by open-cell polylactic acid polymer delivery vehicle. Six
      received autogenous iliac bone graft. Two received carrier alone. Eleven were
      killed 3 months after implantation. One in each group was maintained for 8
      months. OBJECTIVES: To compare recombinant human bone morphogenetic protein-2 and
      open-cell polylactic acid polymer with autogenous iliac bone for inducing
      transverse process fusion in the canine by 3 months and to determine whether
      transverse process decortication and implantation of carrier alone causes
      spontaneous transverse process fusion in the canine. SUMMARY OF BACKGROUND DATA:
      Recombinant human bone morphogenetic proteins have healed segmental long bone
      defects in several models. They have induced interlaminar and facet fusions in
      canines. Interlaminar and facet fusions have occurred after sham decortications
      in canines. Recombinant human bone morphogenetic protein-2 has not been evaluated
      for transverse process fusion in canines. Transverse process fusion is a
      preferred clinical method for achieving posterior lumbar fusion. METHODS: Fusion
      sites were evaluated by serial computed tomography scans. After the dogs were
      killed, explanted spines were subjected to manual testing, mechanical testing,
      high resolution radiography, and histologic analysis. RESULTS: One hundred
      percent of recombinant human bone morphogenetic protein-2-implanted sites had
      solid transverse process fusion by 3 months according to all measures. No
      autografted sites were fused at this interval. Osseous bridging of posterolateral
      gutters occurred in the recombinant human bone morphogenetic protein-2-implanted
      sites after 2 months, the earliest radiographic measure. None of the carrier-only
      sites showed bone formation. CONCLUSIONS: Recombinant bone morphogenetic protein
      2 carried by open-cell polyactic acid polymer is superior to autogenous iliac
      bone for producing radiographically and mechanically solid transverse process
      fusions in canines by 3 months. Spontaneous transverse process fusion does not
      occur in canines after decortication and open-cell polylactic acid polymer
      implantation.

PMID- 8747246
TI  - Telemeterized load measurement using instrumented spinal internal fixators in a
      patient with degenerative instability.
AB  - STUDY DESIGN: In the present study, the loads in an internal spinal fixation
      device were measured in vivo. OBJECTIVES: To determine the implant loads for
      different activities before and after additional anterior stabilization of the
      spine. SUMMARY OF BACKGROUND DATA: Mathematical models exist for predicting
      spinal loads. The intradiscal pressure has been measured for many body positions
      and activities. The loads on internal spinal fixation devices have not been
      measured before in vivo. METHODS: Telemeterized AO spinal internal fixators were
      implanted in a patient with degenerative instability. The implants allow the in
      vivo measurement of three force components and three moments acting in the
      implant. RESULTS: When the patient was lying in relaxed positions, the implant
      loads were small. Before additional anterior stabilization, the loads were also
      small for sitting, standing, and walking. The bending moment in the sagittal
      plane was less than 3 Nm for these activities. The highest loads within the first
      4 weeks after implantation were measured while the patient turned from a supine
      to a lateral position against the advice of the physiotherapist. After anterior
      stabilization, the maximum loads for the relaxed lying positions were altered
      only slightly. Much higher axial forces and bending moments were measured for
      sitting, standing, and walking. The maximum bending moment increased to 5-8 Nm
      for these activities. The implant loads for sitting were not higher than for
      standing. CONCLUSION: Flexion and lateral bending of the upper body and weight
      carrying during sitting, standing, or walking should be avoided in the first few
      months after anterior stabilization.

PMID- 8747247
TI  - Degeneration and aging affect the tensile behavior of human lumbar anulus
      fibrosus.
AB  - STUDY DESIGN: Samples of human lumbar (L3-L4) anulus fibrosus from four different
      anatomic sites (anterior outer, posterolateral inner), ranging from normal to
      severely degenerate, were studied in uniaxial tension and measured for water
      content. OBJECTIVES: To evaluate the effects of aging and degeneration on the
      tensile properties and hydration of the anulus fibrosus in a site-specific
      manner. The relationship between hydration and parameters of the tensile behavior
      were investigated. SUMMARY OF BACKGROUND DATA: Degeneration and aging have been
      shown to be related to dramatic changes in the composition and structure of the
      anulus fibrosus. The associated changes in the tensile, compressive, and shear
      properties of the anulus fibrosus have not been documented. Numerical studies
      using finite element models have attempted to simulate the degenerative process
      by incorporating estimated mechanical properties meant to represent the
      degenerate anulus fibrosus. Their results present findings that suggest that
      altered material properties of the anulus fibrosus affect the mechanics of the
      entire intervertebral disc. METHODS: Samples of human lumbar anulus fibrosus were
      classified by grade of degeneration based on a morphologic grading scheme.
      Multiple layer anulus specimens from four sites in the disc were tested in
      uniaxial tension under quasistatic conditions in a physiologic saline bath. The
      tensile modules, Poisson's ratio, failure stress and strain, the strain energy
      density to failure, and the corresponding hydration were determined for each
      sample. RESULTS: The Poisson's ratio, failure stress, and strain energy density
      of the anulus fibrosus were found to be affected significantly by degeneration,
      with some evidence of a sensitivity of the tensile modulus to grade of
      degeneration. All material properties were found to exhibit a significant and
      greater dependence on site within the disc than on degenerative grade. Weak
      correlations between aging and the Poisson's ratio and strain energy density were
      observed. Water content of anulus fibrosus tissue was not affected by
      degeneration or aging, although correlations with tensile properties were
      observed. CONCLUSIONS: The dramatic changes in morphology, composition, and
      structure that occur in anulus fibrosus with aging and degeneration are
      accompanied by specific variations in the tensile properties, which were
      generally small in magnitude. Position of the anulus fibrosus within the
      intervertebral disc, particularly in the radial direction, appeared to be the
      most important variable affecting anulus fibrosus tensile properties. This
      dependence on position did not change with either aging or degeneration. Results
      from the present study may be useful in future finite element models to assess
      how altered material properties of the anulus fibrosus during degeneration and
      aging may affect the mechanics of the entire intervertebral disc.

PMID- 8747248
TI  - The dominant role of psychosocial risk factors in the development of chronic low
      back pain disability.
AB  - STUDY DESIGN: An inception cohort design was used in which 421 patients were
      evaluated systematically with a standard battery of psychosocial assessment tests
      (Structured Interview for DSM-III-R Diagnosis, Minnesota Multiphasic Personality
      Inventory, and Million Visual Pain Analog Scale) within 6 weeks of acute back
      pain onset. OBJECTIVES: The present study evaluated the predictive power of a
      comprehensive assessment of psychosocial and personality factors in identifying
      acute low back pain patients who subsequently develop chronic pain disability
      problems (as measured by job-work status at 1-year follow-up evaluation). SUMMARY
      OF BACKGROUND DATA: There has been a relative paucity of prospective research in
      the United States comprehensively evaluating potential psychosocial risk factors
      that are associated with those injured workers who subsequently fail to return to
      work and productivity after 1 year because of low back pain disability. Such
      research has been quite limited because of the time and cost involved in
      conducting prospective studies. METHODS: All study patients were symptomatic with
      lumbar pain syndrome for no more than 6 weeks. These acute patients were tracked
      every 3 months, culminating in a structured telephone interview being conducted 1
      year after the initial evaluation to document return-to-work status. RESULTS:
      Logistic regression analyses, conducted to differentiate between patients who
      were back at work after 1 year versus patients who were not because of the
      original back injury, revealed the importance of three psychosocial measures:
      self-reported pain and disability, scores on Scale 3 of the Minnesota Multiphasic
      Personality Inventory, and workers' compensation and personal injury insurance
      status. The model generated correctly classified 90.7% of the cases. Results
      revealed that major psychopathology, such as depression and substance abuse, did
      not precede or cause the development chronic pain disability. CONCLUSIONS: These
      results show the presence of a robust "psychosocial disability factor" that is
      associated with those injured workers who are likely to develop chronic low back
      pain disability problems. Based on these data, a statistical algorithm has been
      generated that can identify those acute patients who will require early
      intervention to prevent the development of chronic disability. The second major
      result is that preinjury or concomitant psychopathology does not appear to
      predispose patients to chronic pain disability, although high rates of
      psychopathology have been shown in chronic low back pain. Future research should
      be directed at emotional vulnerability and psychosocial events in the period
      after the injury that may lead to chronicity.

PMID- 8747249
TI  - The influence of indemnification by workers' compensation insurance on recovery
      from acute backache. North Carolina Back Pain Project.
AB  - STUDY DESIGN: A prospective observational cohort was recruited from 208 randomly
      selected North Carolina practices. OBJECTIVE: To compare the course of
      compensation claimants with gainfully employed patients not so insured from the
      time when they first sought care for acute back pain. SUMMARY OF BACKGROUND DATA:
      The human and financial cost attributable to disabling chronic low back pain
      identified by worker's compensation programs continues to escalate. We explored
      the antecedents to this phenomenon. METHOD: Consecutive patients with acute low
      back pain were interviewed by telephone within 1 week of first seeking care and
      in follow-up calls after 2, 4, 8, 12, and 24 weeks to monitor functional and work
      status. RESULTS: Of the 1633 patients enrolled, 505 were insured by workers'
      compensation. These were compared with 861 who had been employed on any job for
      pay within 3 months of the onset of their backache but whose care was not so
      underwritten. Those with compensable back pain were more likely to categorize
      their tasks as physically demanding and had taken more time off work in the month
      before the baseline interview (P = 0.02). Recovery of the sense of wellness they
      enjoyed before this episode of back pain was delayed (Cox Model: Hazard Ratio =
      0.822; P < 0.001; confidence interval: 0.733, 0.923), but recovery of function or
      return to work was not. This delay was independent of type of health care and
      perception of task demand and beyond that which could be ascribed to the quality
      of back pain. CONCLUSION: Each of these associations is a reproach to the fashion
      in which workers' compensation insurance for regional back pain serves the ethic
      that is its raison d'etre.

PMID- 8747250
TI  - Minnesota Multiphasic Personality Inventory profiles in persons with or without
      low back pain. A 20-year follow-up study.
AB  - STUDY DESIGN: A general health survey including a cross-sectional study of 404
      men and women aged 50 years who underwent follow-up evaluation at ages 60 and 70
      years. OBJECTIVES: The participants completed the Minnesota Multiphasic
      Personality Inventory at age 50 and 60 years and were interviewed at age 60 and
      70 years regarding low back pain experienced in the preceding 10 years. SUMMARY
      OF BACKGROUND DATA: Minnesota Multiphasic Personality Inventory data in low back
      pain patients are derived mainly from selected materials. This study presents
      data from a general population and sheds light on the controversy: "What comes
      first--Minnesota Multiphasic Personality Inventory changes or low back pain?".
      METHODS. Within the frame of a general health survey where the primary aim was to
      study cardiovascular risk factors, the participants completed a shortened Danish
      version of the Minnesota Multiphasic Personality Inventory at age 50 and 60
      years; low back pain data were collected at interviews at age 60 and 70 years,
      and this study focused on the Hypochondriasis-Depression-Hysteria scales of the
      Minnesota Multiphasic Personality Inventory. RESULTS: Presence of low back pain
      from ages 50 to 60 and from ages 60 to 70 years was associated with elevated
      Hypochondriasis-Depression-Hysteria scales at age 50 and 60 years. Profiles
      showing the "conversion-V" configuration were present with a history of low back
      pain, at the 50-year and 60-year Minnesota Multiphasic Personality Inventory
      test. Minnesota Multiphasic Personality Inventory scores collected at age 50
      years were not different between those who did report and those who did not
      report low back pain during the decade from 60 to 70 years, provided that they
      had not experienced low back pain during the period from age 50 to 60 years.
      CONCLUSIONS: Elevations of Minnesota Multiphasic Personality Inventory
      Hypochondriasis-Depression-Hysteria scales were shown in persons with a history
      of low pack pain. The results indicated that low back pain is preceded by
      elevated Minnesota Multiphasic Personality Inventory scales was not supported.

PMID- 8747251
TI  - Formal education and back-related disability. In search of an explanation.
AB  - STUDY DESIGN: The present study is a 2-year prospective study with repeated
      measurements. OBJECTIVES: To examine the association of education with back
      related disability along with four sets of variables that might explain this
      relationship: clinical, behavioral, and environmental factors; occupational
      variables; health care use; and interactions between stressful events and coping
      strategies. SUMMARY OF BACKGROUND DATA: Although education has been found to be
      associated with back-related disability in previous reports, this relationship
      remains to be explained. Examination of this association may yield a better
      understanding of the causes and natural history of disability resulting from back
      pain. METHODS: Subjects were 1213 enrollees of a Health Maintenance Organization
      (HMO) who consulted a primary care physician for back pain in 1989-1990,
      completed a baseline telephone interview, and had a follow-up evaluation after 1
      and 2 years, using a modified version of the Roland-Morris Scale to measure
      disability. RESULTS: Subjects who completed 13 years or more of schooling had
      less disability and a greater decline in their disability over time than those
      who completed less schooling. Occupational characteristics and somatization were
      among the strongest explanatory factors. Cigarette smoking contributed to the
      explanation of the cross-sectional association. CONCLUSIONS: Education is
      associated cross-sectionally and longitudinally with disability resulting from
      back pain. A wide range of variables may mediate the education-back-related
      disability association, including a propensity to report diffuse physical
      symptoms (somatization), lifestyle (e.g., cigarette smoking), and occupational
      factors.

PMID- 8747252
TI  - Psychologic distress and low back pain. Evidence from a prospective study in the
      general population.
AB  - STUDY DESIGN: The present is a prospective population-based cohort study.
      OBJECTIVES: To determine whether psychologic distress in patients free of low
      back pain predicts future new episodes of such pain. SUMMARY OF BACKGROUND DATA:
      An associating between symptoms of depression and anxiety and low back pain has
      been described in cross-sectional studies. It is unclear whether this represents
      cause or effect or whether it is found only in chronic pain sufferers attending
      specialist clinics. There is a need to investigate this prospectively in the
      general population. METHODS: The study population was 4501 adults aged 18-75
      years who responded to a questionnaire survey mailed to all those registered with
      two family practices in the United Kingdom. The survey inquired about low back
      pain during the previous month and included the 12-item General Health
      Questionnaire, a validated schedule for measuring psychologic distress in the
      general population. New episodes of low back pain during the 12 months after the
      survey were identified by two methods--continuous monitoring of all primary care
      consulters and a second postal survey at the end of the 12-month period to
      determine occurrences for which consultation had not been sought. RESULTS: Among
      1638 subjects free of current low back pain in the baseline survey, the
      likelihood of developing a new episode of nonconsulting low back pain was higher
      among those with General Health Questionnaire scores in the upper third of the
      range compared with the lower third (adjusted odds ratio, 1.8 [1.4, 2.4]). This
      could not be explained either by age and gender differences or by general
      physical health. The increased risk persisted when analysis was restricted to
      those who at baseline could not recall ever having had low back pain in the past
      and to those with full-time employment. CONCLUSION: Symptoms of psychologic
      distress in individuals without back pain predict the subsequent onset of new
      episodes of low back pain. We calculate from these data that the proportion of
      new episodes of low back pain that might be attributable to such psychologic
      factors in the general population is 16%.

PMID- 8747253
TI  - Absence resulting from low back trouble can be reduced by psychosocial
      intervention at the work place.
AB  - STUDY DESIGN: A 1-year prospective study in industry, assessing effects of an
      educational pamphlet on various psychosocial parameters and absenteeism resulting
      from low back trouble. OBJECTIVES: To determine the value of distributing an
      educational psychosocial pamphlet to reduce absenteeism resulting from back
      trouble. The pamphlet was designed to alter avoidance behaviors by encouraging a
      positive, active approach. SUMMARY OF BACKGROUND DATA: Attempts to control back
      pain disability have failed. Fear of pain and activity seemingly leads to
      avoidance behaviors than contribute to chronicity and work loss. Avoidance
      behaviors are mediated by attitudes and beliefs; such attitudes and beliefs are a
      reasonable target for educational interventions designed to change
      "inappropriate" behaviors (e.g., extended absenteeism). Health education
      pamphlets are advocated widely but tested rarely. METHODS: Three factories
      participated in the study. Psychosocial data were collected by questionnaires;
      absence data were extracted from company records. A psychosocial pamphlet was
      distributed in one factory; the control subjects received either a nonspecific
      pamphlet or no intervention. The pamphlet emphasized a positive approach to low
      back trouble (reduction of negative beliefs and attitudes). RESULTS: In the
      company whose employees received pamphlets, a significant reduction occurred for
      the number of spells with extended absence and the number of days of absence (70%
      and 60%, respectively) compared with extrapolated values. A concomitant positive
      shift in beliefs concerning the locus of pain control and the inevitable
      consequences of low back trouble was found. CONCLUSION: A simple industrial
      intervention using a psychosocial pamphlet, which was designed to reduce
      avoidance behaviors by fostering positive beliefs and attitudes, successfully
      reduced extended absence resulting from low back trouble.

PMID- 8747254
TI  - Changes in epidural pressure during walking in patients with lumbar spinal
      stenosis.
AB  - STUDY DESIGN: This study was done to assess the pathophysiology of neurogenic
      intermittent claudication by measuring the epidural pressure at walking.
      OBJECTIVES: Changes in epidural pressure during walking in patients with
      neurogenic intermittent claudication and in normal individuals were analyzed.
      SUMMARY OF BACKGROUND DATA: Neurogenic intermittent claudication may be caused by
      compression of the nerve roots or may be a result of nerve root ischemia. The
      exact pathogenesis of neurogenic intermittent claudication is uncertain. METHODS:
      Local epidural pressure changes at the stenotic level during walking were
      analyzed in 12 patients with lumber spinal stenosis and seven normal individuals.
      a flexible pressure transducer was inserted into the epidural space and placed at
      the L4-L5 level. The epidural pressure was monitored continuously during walking.
      The pattern of the pressure change was assessed by gait analysis using a foot
      switch. RESULTS: The pressure was changed during walking. The pressure had a wave
      pattern of increase and decrease, and this pattern was repeated during walking.
      Intermittent pressure increase was seen about 90 times per minute while walking
      at a velocity of 2 km/h. An increase in epidural pressure occurred at the double
      supporting phase in each gait cycle. CONCLUSIONS: The pressure was high in spinal
      stenosis and low in normal individuals. The increase of epidural pressure at
      simple walking was higher than walking with lumbar flexion. Intermittent
      compression to the nerve roots during walking may be a cause of neurogenic
      intermittent claudication.

PMID- 8747255
TI  - Production of chronic compression of the cauda equina in rats for use in studies
      of lumbar spinal canal stenosis.
AB  - STUDY DESIGN: The pathophysiology of lumbar spinal canal stenosis was analyzed
      with a new model in rats. OBJECTIVES: To produce chronic compression of the cauda
      equina in rats for analysis of the pathophysiology of lumbar spinal canal
      stenosis. SUMMARY OF BACKGROUND DATA: Models of compression to date have involved
      acute or subacute compression. A model of chronic compression has not been
      available. METHODS: A stainless steel wire fastened around the spine at L5 in 3
      week-old rats, with a plate inserted against the ventral aspect of the vertebra
      to protect it from the wire. as the rats grew, the wire cut into the spinal
      canal. One year after the operation, canal stenosis was present without paralysis
      of the back limbs. RESULTS: Stenosis seen in sagittal sections, as a percentage
      of the original width, was 51.6 +/- 6.2% (mean +/- standard deviation). In
      histologic analysis of the region near the wire, findings included axonal
      degeneration, demyelination, vacuolar degeneration of the nerve fibers, and
      narrowing the intradural blood vessels with a decrease in their number. Cephalad
      and caudad to the wire, congested intradural blood vessels, degenerative foci
      near these congested vessels, fibrosis around these foci, congested epidural
      vessels, and fibrosis around these vessels were observed. During
      electrophysiologic analysis (six rats with stenosis), the conduction velocity of
      the cauda equina was found to be delayed. CONCLUSIONS: The histologic and
      electrophysiologic findings in this animal model were similar to findings in
      human subjects, so rats prepared in this way should be useful for study of
      chronic compression of the cauda equina.

PMID- 8747256
TI  - A model for acute, chronic, and delayed graded compression of the dog cauda
      equina. Presentation of the gross, microscopic, and vascular anatomy of the dog
      cauda equina and accuracy in pressure transmission of the compression model.
AB  - STUDY DESIGN: A new model for controlled, graded compression of the dog cauda
      equina was developed using the dog lumbar spine. The model was defined regarding
      macroscopic, microscopic, and vascular anatomy and regarding accuracy in pressure
      transmission. OBJECTIVES: The study was performed to develop a model for
      controlled, graded compression that would allow for acute, chronic, and delayed
      compression. SUMMARY OF BACKGROUND DATA: There has been an increasing interest
      for the reactions of the spinal nerve roots to mechanical deformation. The
      previously used models have had limitations regarding the duration and the onset
      of the compression and possibilities for a controlled variation of the
      compression pressure on chronically compressed nerve roots. METHODS: Macroscopic
      examination, light microscopy, and ink injection of the vasculature was used to
      assess the anatomic characteristics of the nerve tissue and the vasculature of
      the cauda equina in the dog lower lumbar spine. The relation between known
      pressures in the compression balloon used to compress the cauda equina and the
      pressure in the central thecal sac was assessed by measuring the pressure in an
      artificial thecal sac with a pressure transducer. RESULTS. The neural and
      vascular anatomy was found to have a close resemblance to the human cauda equina.
      The pressure in the thecal sac was within 5% of the pressure in the compression
      balloon at various pressures between 0-200 mm Hg. CONCLUSION: The presented model
      provides a good pressure transmission to the dog cauda equina, which has an
      anatomy that closely resembles the human cauda equina. The model may be well
      suited for physiologic studies of cauda equina compression. A double-balloon
      system may provide unique opportunities to induce chronic compression and delayed
      compression, i.e., additional compression after a certain time of chronic
      compression to resemble the changes in pressure that are characteristic for
      neurogenic claudication.

PMID- 8747257
TI  - Two-level spinal stenosis in minipigs. Hemodynamic effects of exercise.
AB  - STUDY DESIGN: Twenty-two Gottingen minipigs were trained to run on a treadmill.
      Two-level lumbar spinal stenosis was created in 12 pigs, 10 were unoperated
      control subjects. Blood flow of the spinal cord and nerve roots was determined
      with microspheres at rest, during exercise, and after exercise. OBJECTIVES: To
      study the effect of lumbar spinal stenosis and exercise on blood flow of spinal
      neural tissue. SUMMARY OF BACKGROUND DATA: Neurogenic claudication, the key
      symptom of lumbar spinal stenosis, may be caused by vascular impairment or
      mechanical distress of neural tissue during exercise. Experimental compression of
      the cauda equina causes reversible nerve root edema, stasis, blood flow decrease,
      and compromised neural function. The vascular pathophysiology of spinal stenosis
      during exercise has not been studied previously. METHODS: Pigs were trained daily
      for 3 months. Two-level 25% lumbar spinal stenosis was introduced by placement of
      stenosing bands around the dural sac. Neurologic function was monitored before
      surgery by evoked potentials and after surgery by the Tarlov score. Regional
      blood flow in lumbosacral neural tissue was measured 3 days after chronic
      catheterization using microspheres at rest, during exercise at 3 km/h for 15
      minutes, and at rest 30 minutes after exercise. RESULTS: Blood flow of grey and
      white matter increased during exercise in both groups, with no differences
      between groups. slight hyperemia prevailed after exercise in white matter of the
      stenotic area but not in grey matter. Nerve root blood flow was largely unchanged
      in control subjects during exercise but was reduced in spinal stenosis at rest,
      further depressed during exercise, and normalized after exercise. Dural blood
      flow was elevated throughout. CONCLUSION: The study suggests that exercise
      induced impairment of spinal nerve root blood flow plays a role in the
      pathophysiology of neurogenic claudication.

PMID- 8747259
TI  - Epidemiology introduction. 1995 Focus Issue Meeting on Fusion.

PMID- 8747258
TI  - Risk of myocardial infarction among subjects visiting a doctor because of back
      disorder. A case--control study in Finnish farmers.
AB  - STUDY DESIGN: A nested case-control study was made to analyze the correlation
      between back trouble and myocardial infarction. OBJECTIVES: The purpose of the
      present study was to determine whether individuals visiting a doctor because of
      back trouble have an increased risk for myocardial infarction. SUMMARY OF
      BACKGROUND DATA: According to previous results, back pain precedes myocardial
      infarction in young and middle-aged male farmers. There are no previous results
      concerning the risk of myocardial infarction among patients visiting a doctor
      because of back pain. METHODS: The basic cohort includes 3172 Finnish farmers.
      Those having myocardial infarction from February 1, 1980 through December 31,
      1992 were considered case studies. Three matched control subjects were selected
      for every case subject. The final group had 83 case subjects and 249 matched
      control subjects. Case subjects and control subjects were compared according to
      doctor visits because of back complaint during the follow-up period, which began
      February 1, 1980 and ended on the date of myocardial infarction of each case
      subject. RESULTS: Fewer case subjects than control subjects visited a doctor
      because of back disorders during the follow-up period. This was especially true
      for nonspecific back pain (odds ratio = 0.51; confidence interval = 0.25-1.05).
      CONCLUSION: Atherosclerosis is not a probable cause of any kind of back pain
      among individuals visiting a general practitioner because of back complaint.

PMID- 8747260
TI  - Lumbar spinal fusion. Surgical rates, costs, and complications.
AB  - STUDY DESIGN: Literature review. OBJECTIVES: To assess the frequency of lumbar
      fusion procedures in the United States; changes in the incidence of fusion in the
      past 12 years; variations in fusion procedure rates among geographic regions of
      the nation and between the United States and other countries; costs of lumbar
      fusion; and rates of infrequent outcomes, which are best estimated from
      administrative data, including complications and deaths. SUMMARY OF BACKGROUND
      DATA: Several recent analyses have shown that lumbar spine fusion procedures are
      done more frequently and are associated with increased costs and rates of
      complications. METHODS: Qualitative review of the literature on frequency, costs,
      and complications of lumbar fusion. RESULTS AND CONCLUSIONS: The rates of lumbar
      fusion procedures are increasing rapidly, particularly for lumbar spinal stenosis
      in older patients. Fusion rates appear to vary markedly among individual
      surgeons, among small and large geographic regions in the nation, and between the
      United States and England. These variations are considerably more dramatic than
      variations in rates of lumbar discectomy. Fusion for spinal stenosis with
      spondylolisthesis is, as expected, associated with higher costs and complication
      rates than is decompressive surgery for this indication without fusion. Fusion
      rates are increasing rapidly and show dramatic geographic variations, suggesting
      differences in opinion within the surgical community regarding the appropriate
      indications for lumbar fusion. Studies are needed to determine whether the
      frequency, costs, and complications of lumbar fusion are justified by clinical
      benefits.

PMID- 8747261
TI  - Biomechanics introduction. 1995 Focus Issue Meeting on Fusion.

PMID- 8747262
TI  - Biomechanics of fusion and stabilization.
AB  - STUDY DESIGN: Literature review. OBJECTIVES: To assess the state of the art in
      the biomechanics of fusions, fusion materials, and the use of instrumentation by
      critically reviewing the literature as modified by group discussion. SUMMARY OF
      BACKGROUND DATA: A considerable body of knowledge addresses these issues based on
      in vitro biomechanical testing and mathematical models. Much biomechanical
      information is available regarding the biomechanical behavior of the graft
      material, the fusion, and the instrumentation. Biomechanical testing and finite
      element analyses remain to be done on semirigid devices, interbody spacers, and
      artificial discs. METHODS: The literature was reviewed to analyze papers written
      on the following topics: graft material, in vitro tests of instrumentation,
      device evaluation using artificial spine models, in vivo human studies, animal
      models, finite element studies, effects of rigidity, and bone adaptive
      remodeling. RESULTS: One hundred forty-one modern articles were reviewed and
      their data analyzed. Much important insight has come from biomechanical studies.
      CONCLUSIONS: Fusions are largely successful. Biomechanical data is complete
      except for some of the latest devices.

PMID- 8747263
TI  - Biologic issues in lumbar spinal fusion. Introduction. 1995 Focus Issue Meeting
      on Fusion.

PMID- 8747264
TI  - Biologic factors affecting spinal fusion and bone regeneration.
AB  - STUDY DESIGN: Literature review. OBJECTIVES: This article reviews the existing
      data on the multiplicity of local and systemic factors affecting lumbar spinal
      fusion and the general biology of bone regeneration. SUMMARY OF BACKGROUND DATA:
      Arthrodesis is one of the most commonly performed, yet incompletely understood,
      procedures in spinal surgery. There exists a paucity of knowledge about the basic
      biology involved in achieving a successful fusion. METHODS: Medline and manual
      search of all relevant articles were performed and summarized. RESULTS: The
      success or failure of spinal fusion may be influenced by a host of local and
      systemic factors. CONCLUSIONS: Future research should focus on expanding our
      existing knowledge pertaining to the basic biology of bone regeneration specific
      to spinal fusion.

PMID- 8747265
TI  - Biologic enhancement of spinal fusion.
AB  - STUDY DESIGN: Literature review. OBJECTIVES: To review the available animal and
      clinical data on biologic enhancements of spinal fusion. SUMMARY OF BACKGROUND
      DATA: Lumbar spinal arthrodesis may result in pseudarthrosis in 5% to 35% of
      patients. Although much research has focused on the mechanical factors affecting
      spinal fusion, the use of internal fixation has not eliminated the problem of
      spinal nonunions. Accordingly, biologic enhancement of spinal fusion has become
      an important focus of spinal research. METHODS: Medline and hand searches.
      RESULTS: Electric stimulation, bone graft substitutes, and bone growth factors
      have been researched most extensively. Electric stimulation and early attempts at
      bone graft substitutes (allograft, xenograft) have yielded variable results. The
      feasibility of biologic enhancement of spinal fusion with osteoinductive growth
      factors has been shown in animals. CONCLUSION: The efficacy of bone growth
      factors for lumbar fusion remains to be definitively established in humans.

PMID- 8747266
TI  - Indications for lumbar spinal fusion. Introduction. 1995 Focus Issue Meeting on
      Fusion.

PMID- 8747267
TI  - The treatment of degenerative lumbar disorders. A critical review of the
      literature.
AB  - STUDY DESIGN: A literature review. OBJECTIVES: To clarify the surgical
      indications for spinal fusion in the various lumbar conditions. SUMMARY OF
      BACKGROUND DATA: This article summarizes the published literature regarding the
      treatment of lumbar degenerative conditions. Retrospective and prospective
      studies regarding the treatment of nonspecific low back pain, disc herniation,
      spinal stenosis, isthmic spondylolisthesis, facet syndrome, discogenic pain, and
      lumbar spondylosis are reviewed. METHODS: A review of the English Medical
      Literature regarding the treatment of low back pain, disc herniation, spinal
      stenosis, spondylolisthesis, discogenic pain, and lumbar spondylosis was
      performed. RESULTS AND CONCLUSIONS: Past research does not support the use of
      spinal fusion for nonspecific low back pain. Fusion is rarely indicated for
      primary disc herniation but may have a role in recurrent herniations. Specific
      guidelines regarding fusion in spinal stenosis and spondylolisthesis are
      described based on the literature. Less rigorous data are presented for
      indications for fusion in facet joint syndrome, discogenic pain, and lumbar
      spondylosis. Spinal fusion plays an important role in the treatment of
      degenerative disorders of the lumbar spine, and the indications for this
      procedure can be refined by reviewing the existing literature.

PMID- 8747268
TI  - Is fusion indicated for lumbar spinal disorders?
AB  - STUDY DESIGN: A review of relevant literature and clinical experience with lumbar
      spinal disorder. OBJECTIVES: To discuss the indications for fusions and lumbar
      spinal disorders. SUMMARY OF BACKGROUND DATA: Fusion of the lumbar spine is
      performed frequently, but indications have not been defined clearly. The
      literature and the authors' experience with these indications are reviewed.
      METHODS: A comprehensive review of the literature and the authors' clinical
      experience with lumbar spinal instability was critically examined. Specifically,
      the role of fusion, with or without instrumentation, versus decompression alone
      was assessed. From this, a set of definitive and relative indications for spinal
      arthrodesis in a variety of disorders of the lumbar spine could be established.
      RESULTS: Once the diagnosis of lumbar spinal instability is established, fusion
      is indicated. However, fusion without spinal instrumentation has a high
      pseudarthrosis rate and poorer patient outcome. This spinal instrumentation
      should be used as an adjunct when considering spinal arthrodesis. CONCLUSIONS:
      Definitive indications for spinal fusions are trauma, tumor and infection,
      iatrogenic instability, or ischemic spondylolisthesis. Relative indications for
      fusions are degenerative spondylolisthesis, abnormal movement visualized on
      dynamic films with appropriate pain or neurologic deficit, and mechanical pain.
      Lumbar fusion is rarely indicated for routine discectomy, abnormal results of
      radiography without appropriate clinical findings, or stable spinal stenosis.

PMID- 8747269
TI  - The indications for lumbar spinal fusion with and without instrumentation.
AB  - STUDY DESIGN: Literature review. OBJECTIVES: A review, analysis, and discussion
      of the extensive literature on lumbar spinal fusion were done to attempt to place
      in perspective the indications and success rate for lumbar spinal fusion with and
      without instrumentation. SUMMARY OF BACKGROUND DATA: A wide variety of lumbar
      spinal conditions have been managed by spinal fusion. Results appear better when
      the diagnosis is very specific and related to definable instability or deformity
      in patients with a stable psychologic state. METHODS: Search of literature.
      RESULTS: Success rates are higher in isthmic spondylolisthesis, unstable spinal
      stenosis syndromes (degenerative spondylolisthesis, degenerative scoliosis), and
      in patients with objective segmental instability. Variable success rates are
      reported for disc-related low back pain conditions and in patients with failed
      previous surgery. Instrumentation appears to be beneficial in situations where
      complex deformities or obvious instability is present. When applied for other
      diagnoses (e.g., internal disc disruption), results appear no better than with
      traditional surgical techniques. CONCLUSIONS: The outcome of lumbar spinal fusion
      depends on careful assessment of the anatomic cause of pain and of the patient's
      functional state and expectations.

PMID- 8747270
TI  - Use of internal fixation instrumentation. Introduction. 1995 Focus Issue Meeting
      on Fusion.

PMID- 8747271
TI  - Internal fixation (pedicle screw fixation) for fusions of the lumbar spine.
AB  - STUDY DESIGN: Literature review. OBJECTIVES: To illustrate the indications and
      potential complications of pedicle screw application in the lumbar spine. SUMMARY
      OF BACKGROUND DATA: Except for the treatment of severe spondylolisthesis (grades
      3 and 4) at L5-S1, using autogenous bone graft and with device removal often
      fusion is obtained. Pedicle screw devices labeled for stabilizing the lumbar
      spine or correcting deformities in fusion procedures are currently considered
      Class III medical devices by the Food and Drug Administration, that is,
      investigational or experimental forms of spinal fixation. Recent clinical studies
      have attested to their usefulness and safety by qualified surgeons for selected
      surgical indications. METHODS: Literature synthesis. RESULTS: Segmental fixation
      increases the fusion rate and clinical success of indicated patients undergoing
      the procedure in lumbar spine operations, as it does in the treatment of fusion
      of long bone injuries, scoliosis, and other comparable surgeries. CONCLUSION:
      With this technology, surgeons can effectively reduce the pseudarthrosis rate,
      improve patient satisfaction and results of functional studies, and ultimately
      reduce the long-term cost to society as a result of effective initial posterior
      lumbar spine surgery.

PMID- 8747272
TI  - Selection of the optimal procedure to achieve lumbar spinal fusion. Introduction.
      1995 Focus Issue Meeting on Fusion.

PMID- 8747273
TI  - Interbody, posterior, and combined lumbar fusions.
AB  - STUDY DESIGN: This is a review article on the different approaches used to obtain
      fusion of the lumbar spine. OBJECTIVE: To describe certain conceptual and
      technical aspects related to the various fusion techniques that are used commonly
      for lumbar spine disorders and to discuss the expected clinical results. SUMMARY
      OF BACKGROUND DATA: There are differences of opinion among surgeons concerning
      the preferred method for lumbar spine fusion, whether done for deformity,
      disease, trauma, or degeneration. METHODS: A review of the literature combined
      with personal experience formed the basis of this article. RESULTS: At the
      present time, analysis of the literature does not indicate that one form of
      fusion is significantly better than another for degenerative conditions of the
      lumbar spine. There is recent evidence suggesting better outcomes (as distinct
      from subjective opinion alone) are obtained after anterior interbody fusion than
      after posterolateral fusion with internal fixation, despite a higher fusion rate
      in the latter group. There is evidence that suggests late spinal stenosis
      adjacent to a fusion is more likely to occur with posterior fusion procedures
      than with anterior fusion alone. CONCLUSIONS: Significant potential complications
      are associated with all techniques, particularly neurologic damage with posterior
      interbody fusion, and vascular injury with anterior interbody fusion. Spinal
      fusion procedures should only be done by surgeons with the necessary training and
      expertise.

PMID- 8747274
TI  - Protein transport via amino-terminal targeting sequences: common themes in
      diverse systems.
AB  - Many proteins that are synthesized in the cytoplasm of cells are ultimately found
      in non-cytoplasmic locations. The correct targeting and transport of proteins
      must occur across bacterial cell membranes, the endoplasmic reticulum membrane,
      and those of mitochondria and chloroplasts. One unifying feature among
      transported proteins in these systems is the requirement for an amino-terminal
      targeting signal. Although the primary sequence of targeting signals varies
      substantially, many patterns involving overall properties are shared. A recent
      surge in the identification of components of the transport apparatus from many
      different systems has revealed that these are also closely related. In this
      review we describe some of the key components of different transport systems and
      highlight these common features.

PMID- 8747275
TI  - The interaction between human Fc gamma RI and the gamma-chain is mediated solely
      via the 21 amino acid transmembrane domain of Fc gamma RI.
AB  - We have established a biological assay to investigate the nature of the non
      covalent interaction between two integral type I membrane proteins, Fc gamma RI
      and gamma-chain. Fc gamma RI, the human high affinity receptor for immunoglobulin
      G (IgG), is expressed on the surface of macrophages and monocytes and mediates a
      broad range of important immunological functions. Fc gamma RI relies on a
      functional interaction with a second integral type I membrane protein, gamma
      chain, to mediate many of these functions. For example, Fc gamma RI can only
      mediate phagocytosis of IgG-coated particles in COS cells when co-expressed with
      gamma-chain. We have previously shown that the cytoplasmic domain of Fc gamma RI
      is not necessary for this functional interaction. In this study we have used the
      phagocytosis assay to investigate the role of the transmembrane region of Fc
      gamma RI in mediating this functional interaction with gamma-chain by using
      mutant and chimeric forms of the receptor. Three mutants, which introduce or
      remove charged residues from a conserved 10 amino acid stretch of amino acids in
      the proximal transmembrane region of Fc gamma RI, were able to mediate
      phagocytosis of IgG-coated particles. In contrast, two chimeric receptors, In
      which 21 of the amino acids in the distal transmembrane region of Fc gamma RI
      were replaced with the transmembrane region of the related receptors CD2 or LFA3,
      were expressed but failed to interact functionally with gamma-chain to mediate
      phagocytosis. Thus, these mutants demonstrate that the interaction between human
      Fc gamma RI and gamma-chain is mediated solely via these 21 amino acids in the
      transmembrane domain of Fc gamma RI.

PMID- 8747276
TI  - Mutational analysis and molecular modelling of an amino acid sequence motif
      conserved in antiporters but not symporters in a transporter superfamily.
AB  - Elements of a 'G X8 G X3 G P X2 G G' amino acid sequence motif were conserved in
      the fifth predicted membrane-spanning domains of 31 antiporters, but none of 27
      symporters or uniporters that together comprise a 'superfamily' of structurally,
      related transport proteins. Molecular modelling and mechanics predicted that the
      GP dipeptide of this motif bends the antiporters' fifth transmembrane helices,
      and that the repeating pattern of glycine residues forms a pocket, devoid of side
      chains, on the surface of these helices. The glycine residue in the motif's GP
      dipeptide was conserved in 90% of these antiporters with alanine being the only
      observed substitution. Replacement of the glycine residue of the GP dipeptide
      with alanine and serine reduced the level of tetracycline resistance conferred by
      TetA(C), a tetracycline/H+ antiporter, by 74 and 81%, respectively. All other
      substitutions totally abolished resistance to tetracycline. In contrast,
      replacement of the glycine residue of the GP dipeptide did not abolish increased
      susceptibility to cadmium, another phenotype conferred by TetA(C) independent of
      resistance to tetracycline. These results suggest that the glycine of the GP
      dipeptide is necessary for the tetracycline/H+ antiport activity of TetA(C),
      rather than its expression, stability, or general three-dimensional structure.

PMID- 8747277
TI  - Calcium-induced relocation of annexins IV and V in the human osteosarcoma cell
      line MG-63.
AB  - In cell culture, human osteoblasts and the osteosarcoma cell line MG-63 express
      annexins I, II, IV, V and VI. Small proportions of annexins IV and V are lost
      from MG-63 cells into the culture medium in a sedimentable form. however, the
      bulk of these annexins is intracellular. In non-confluent cells 3 days after
      passaging, annexin IV and annexin V are strongly present throughout the nucleus
      and are also present in the cytoplasm. On elevation of the intracellular calcium
      concentration with the lonophore ionomycin, the intranuclear pools of annexin IV
      in 38 +/- 4% of cells and annexin V in 70 +/- 5% of cells show relocation to the
      nuclear membrane within 40 s. Extracellular ATP, which causes a transient
      increase in the cytosolic free calcium concentration by acting at P2
      purinoceptors, also causes relocation of the intranuclear pool of annexin IV in
      22 +/- 4% of cells and of annexin V in 38 +/- 8% of cells. After stimulation no
      significant reversal of the relocation is observed. Elevation of intracellular
      calcium with ionophore and ATP also causes relocation of the cytoplasmic pools of
      annexins IV and V. The results support a role for annexins at cellular membranes
      in response to elevation of cytosolic calcium levels.

PMID- 8747278
TI  - An investigation into the role of N-glycosylation in the functional expression of
      a recombinant heteromeric NMDA receptor.
AB  - The effect of N-glycosylation on the assembly of N-methyl-D-aspartate (NMDA)
      heteromeric cloned receptors was studied. Thus human embryonic kidney (HEK) 293
      cells were cotransfected with N-methyl-D-aspartate R1 (NR1) and N-methyl-D
      aspartate R2A (NR2A) clones and the cells grown post-transfection in the presence
      of tunicamycin (TM). TM treatment resulted in a decrease of the NR1 subunit with
      M(r) 117 000 with a concomitant increase in a M(r) 97 000 immunoreactive species
      previously identified as the non-N-glycosylated NR1 subunit. In parallel, TM
      caused a dose-dependent inhibition of [3H]MK801 binding to the expressed receptor
      which was a result of an approximate four-fold reduction in the Dissociation
      Constant (KD) but with no change in the number of binding sites (Bmax). NMDA
      receptor cell surface expression was unchanged following TM treatment but it did
      result in a decrease in the percentage cell death post-transfection compared to
      control samples. The removal of TM from the cell culture media resulted in a
      return to the control KD value for [3H]MK801 binding and partial reglycosylation
      of newly synthesized NR1 subunit. These results demonstrate that N-glycosylation
      is requisite for the efficient expression of functional NR1/NR2A receptors.
      Furthermore, they suggest that N-glycosylation may be important for the correct
      formation of the channel domain of the NR1/NR2A receptor.

PMID- 8747280
TI  - A quantitative assay to determine the amount of signal peptidase I in E. coli and
      the orientation of membrane vesicles.
AB  - The number of Signal Peptidase I (SPasel) molecules per E. coli cell was
      determined using western blot techniques. Different strains were found to contain
      approximately 1000 SPasel molecules per cell during exponential growth. Based on
      the activity of SPasel in vitro it could be estimated that this amount is
      sufficient to process all translocated precursors. SPasel did not appear to be
      under growth phase dependent control, but was constitutively expressed. The
      quantitative western blot technique was also used to establish the orientation
      and intactness of isolated inner membrane vesicles.

PMID- 8747279
TI  - Agonist-induced displacement of quinacrine from its binding site on the nicotinic
      acetylcholine receptor: plausible agonist membrane partitioning mechanism.
AB  - It was previously demonstrated that high concentrations of cholinergic agonists
      such as acetylcholine (ACh), carbamylcholine (CCh), suberyldicholine (SubCh) and
      spin-labelled acetylcholine (SL-ACh) displaced quinacrine from its high-affinity
      binding site located at the lipid-protein interface of the nicotinic
      acetylcholine receptor (AChR) (Anas, H. R. and Johnson, D. A. (1995)
      Biochemistry, 34, 1589-1595). In order to account for the agonist self-inhibitory
      binding site which overlaps, at least partially, with the quinacrine binding
      site, we determined the partition coefficient (Kp) of these agonists relative to
      the local anaesthetic tetracaine in AChR native membranes from Torpedo
      californica electric organ by examining (1) the ability of tetracaine and SL-ACh
      to quench membrane-partitioned 1-pyrenedecanoic acid (C10-Py) monomer
      fluorescence, and (2) the ability of ACh, CCh and SubCh to induce an increase in
      the excimer/monomer ratio of C10-Py-labelled AChR membrane fluorescence. To
      further assess the differences in agonist accessibility to the quinacrine binding
      site, we calculated the agonist concentration in the lipid membrane (CM) at an
      external agonist concentration high enough to inhibit 50% of quinacrine binding
      (IC50), which in turn was obtained by agonist back titration of AChR-bound
      quinacrine. Initial experiments established that high agonist concentrations do
      not affect either transmembrane proton concentration equilibria (pH) of AChR
      membrane suspension or AChR-bound quinacrine fluorescence spectra. The agonist
      membrane partitioning experiments indicated relatively small (< or = 20) Kp
      values relative to tetracaine. These values follow the order: SL-ACh>SubCh>>CCh
      ACh. A direct correlation was observed between Kp and the apparent inhibition
      constant (Ki) for agonists to displace AChR-bound quinacrine. Particularly,
      agonist with high KpS such as SL-ACh and SubCh showed low Ki values, and this
      relationship was opposite for CCh and ACh. The calculated CM values indicated
      significant (between 7 and 54 mM) agonist accessibility to lipid membrane. By
      themselves, these results support the conjecture that agonist self-inhibition
      seems to be mediated by the quinacrine binding site via a membrane approach
      mechanism. The existence of an agonist self-inhibitory binding site, not located
      in the channel lumen would indicate an allosteric mechanism of ion channel
      inhibition; however, we can not discard that the process of agonist self
      inhibition can also be mediated by a steric blockage of the ion channel.

PMID- 8747281
TI  - Replantation of a large amputated segment of the face: a new technique.

PMID- 8747282
TI  - Gracilis donor site morbidity.
AB  - Donor site morbidity in 104 cases of gracilis free tissue transfer was examined
      through a retrospective chart review and mail survey. Fifty-one females and 53
      males with an average age of 23 years comprised the study group. Forty-three were
      under age 18. In-hospital donor site complications occurred in 10 patients. There
      was excessive pain in 4, wound infections in 3, hemorrhage in 2, and temporary
      nerve palsy in 1. Early complications were more common in the pediatric group.
      Sixty-two surveys were returned from patients detailing late complications where
      they graded parameters between 0 and 10 where 0 was "none" and 10 was "worst
      imaginable." The highest average score was 5.12 reported for noticeability of the
      scar. There was a significant difference between adults and children for
      sensitivity, tightness, notice-ability, and ugliness of the scar. More than half
      the respondents had no complaints about their donor site scar. Fifteen percent of
      patients reported temporary reduction of leg strength with a men duration of 6
      months.

PMID- 8747283
TI  - Use of ultrasonography to evaluate muscle thickness and blood flow in free flaps.
AB  - The purpose of this study was to investigate the common belief that a
      microvascular transfer of a non-innervated free muscle flap loses muscle bulk
      over time. Sixteen patients (latissimus dorsi = 8, rectus abdominis = 7, and
      gracilis muscle = 1) were evaluated an average of 41 months after free flap
      transfer. Latissimus dorsi and lower extremity flaps displayed significantly more
      swelling than the other flaps. Flap bulk was measured by ultrasound. The mean
      thickness of upper extremity flaps was 10.3 +/- 1.8 mm (control muscles 11.8 +/-
      2.8), lower-extremity 14.5 +/- 3.7 mm (control muscles 10.9 +/- 0.7), latissimus
      dorsi 14.3 +/- 2.2 mm (control muscles 10.3 +/- 0.8, P = 0.018), and rectus
      abdominis 11.2 +/- 1.2 mm (control muscles 12.4 +/- 1.9). Color Doppler
      ultrasonography was used to detect the pedicles of the free flaps and also to
      measure the peak velocity of blood flow intramuscularly and in the pedicles. In
      the upper extremities (n = 5) the pedicles could be found in only 20% of cases
      whereas in the lower extremities (n = 11) 91% of pedicles were located. (P =
      0.013). Peak flow within the free flaps was significantly higher in the lower
      extremity (50% of the peak flow of the common femoral artery) than in the upper
      extremity (5% of the peak flow of the common femoral artery, P = 0.013). This
      study demonstrated that non-innervated free muscle flaps in the extremities
      maintain the original muscle thickness, although lower extremity and latissimus
      dorsi flaps have a trend to be thicker. Most pedicles of free muscle flaps in the
      upper extremities could not be located by ultrasound. However, flaps in the lower
      extremities most often have patent pedicles and also more vigorous intramuscular
      blood flow.

PMID- 8747284
TI  - Refinements in the one-stage procedure for management of chronic osteomyelitis.
AB  - Posttraumatic osteomyelitis remains a frequent problem and requires aggressive
      surgical treatment to be cured. Radical debridement of all involved soft and hard
      tissues, obliteration of dead space, and neovascularization of the involved area
      are obligatory for successful management of the disease. Microvascular free
      tissue transfer provides the necessary tissue bulk and neovascularization to
      reconstruct the resulting defect. The transplanted muscle can be optimally
      mobilized and adjusted in size to obliterate the dead space in contrast to local
      transposition flaps. This is facilitated by smoothening the bony cavity using a
      rotating drill system. With an optimal interface between the muscle and the wall
      of the cavity, small foci of infection can be eliminated. Moreover after free
      muscle transfer, the optimal environment for secondary bone reconstruction is
      created. These principles of radical debridement combined with muscle transfer
      for dead space obliteration, are generally accepted in literature. Nevertheless
      to achieve this goal several different treatment schedules of repetitive
      debridements, prolonged antibiotic regimes, and finally various flap transfers
      have been advocated. We present 16 patients with chronic osteomyelitis treated
      with radical debridement and immediate free muscle transfer using the latissimus
      dorsi muscle preferably. Postoperatively an antibiotic course of only 12 days was
      given. With a mean follow-up of 2 years all patients remained symptom free.
      Therefore, our results indicate that this long-term problem can be solved by a
      one-stage procedure using a free flap combined with a short course of
      antibiotics. However definite conclusions should be reserved for 20 years.

PMID- 8747285
TI  - Immunosuppressive effect of monoclonal antibodies to ICAM-1 and LFA-1 on
      peripheral nerve allograft in mice.
AB  - This study evaluated the immunosuppressive effect of monoclonal antibodies
      against cell surface molecules in a murine peripheral nerve allograft model.
      After nerve allografting, 18 recipients were treated with both anti-intercellular
      adhesion molecule-1 (ICAM-1) and anti-lymphocyte function-associated molecule-1
      (LFA-1) monoclonal antibodies in low or high dose. Nerve allografts were
      harvested at 8 weeks for histologic and morphometric evaluation. Recipients were
      subsequently challenged with skin grafts at 9 weeks and a cytotoxic assay at 12
      weeks. The majority of the antibody-treated allografts (13 of 18) showed
      excellent regeneration comparable to the autografts with preservation of the
      normal nerve architecture and scant cellular infiltrate. All untreated allografts
      demonstrated severe structural disorganization with cellular infiltrate
      consistent with acute rejection. In the high dose group, the mean skin graft
      survival time from nerve donor mice, but not third-party mice, was significantly
      prolonged. (17.5 vs. 11.3 days). Similarly, the cytotoxic activity against nerve
      donor alloantigen was significantly suppressed. These preliminary findings
      suggest that antibody therapy alone can facilitate nerve regeneration in a murine
      nerve allograft model.

PMID- 8747286
TI  - Nerve regeneration in different types of grafts: experimental study in rabbits.
AB  - The nerve regeneration patterns of five different types of grafts were studied in
      40 rabbits. Conventional nerve autografts, vascularized nerve autografts, fresh
      nerve allografts, frozen nerve allografts, and muscle autografts were sutured to
      a 1.5 cm gap in the sciatic nerve and compared with normal nerves and nerves with
      a 3 cm gap. Regeneration was evaluated by means of electromyography, light and
      electron microscopy. Quantitative data from morphometric analysis of axonal
      diameter and myelination were statistically analyzed. Results 5 months after
      grafting showed no significant differences between the conventional and
      vascularized nerve autografts. There were no significant differences between
      frozen nerve allografts and muscle autografts. The best regeneration was achieved
      with autografts.

PMID- 8747287
TI  - Comparison of the telescoping anastomotic technique with the end-to-end technique
      utilizing vein grafts for venous defects: short- and long-term results.
AB  - The telescoping anastomotic technique was used for both anastomoses of vein
      grafts placed in the rat left epigastric vein in an effort to make the
      anastomosis easier and faster. Vein grafting in the right epigastric vein was
      completed using the conventional technique. The 20 rats with 20 left and 13 right
      vein grafts, which were patent at 3 weeks, were seen again 3 months
      postoperatively to compare the two techniques with regard to long-term stenosis
      and histological changes. Patency of the grafts 2 hr postoperatively was also
      compared between the two techniques in another 25 rats to eliminate the influence
      of recanalization on patency. All the vein grafts, which had been patent 3 weeks
      postoperatively, remained patent after 3 months and no statistically significant
      difference was found between the telescoping and conventional technique in the
      degree of stenosis. The vein grafts 2 hr postoperatively were all patent in both
      groups.

PMID- 8747288
TI  - Effect of ischemia and three different perfusion solutions on the rabbit
      epiphyseal growth plate.
AB  - An isolated vascularized knee joint model was used (1) to determine the minimum
      ischemia time that produced growth retarding damage to the epiphyseal plate and
      (2) to evaluate whether intra-arterial perfusion could reduce the ischemia
      damage. Experiment 1 consisted of 31 rabbits in 5 groups: 0, 2,4,6, and 8 hr of
      warm ischemia produced by clamping the pedicle. Experiment 2 consisted of 18
      rabbits in which 10 ml of one of (1) Euro-Collins, (2) University of Wisconsin
      solution, or (3) heparinized blood were perfused through the joint without
      ischemia. Experiment 3 consisted of 21 rabbits in which one of the three
      solutions was perfused for a short period during 6 hr of ischemia. Growth of the
      tibia was followed radiographically every month over 3 months, and the growth
      plates were evaluated histologically after sacrifice. Results showed that at
      least 6 hr of ischemia was needed before longitudinal growth was reduced; less
      ischemia time caused overgrowth. Histologic damage was found in all animals to
      some degree. Perfusion alone without ischemia had no detrimental effect on growth
      or histology. The growth reduction at 6 hr of ischemia was minimized by perfusion
      with every solution. Heparinized blood was the most effective and Euro-collins
      was the least effective.

PMID- 8747289
TI  - Harvesting of the latissimus dorsi muscle: a small animal model for seroma
      formation.
AB  - A common complication of soft tissue dissection and muscle harvesting is seroma
      formation. In order to manage and understand the formation of seromas, we
      developed a small animal model for seromas in the Sprague Dawley rat. Skin flaps
      and subcutaneous tissue were elevated and the latissimus dorsi muscle was
      harvested in 20 animals. Eighteen of the 20 rats (90%) formed clinically
      significant seromas. Sixteen animals had associated skin flap necrosis and 12
      required serial drainage for recurrent seromas. At necropsy, gross capsular
      formation occurred in all animals who developed seromas. Microscopically, a
      fibrous capsule enveloping the seroma was seen associated with a local chronic
      inflammatory cell infiltrate. We conclude: (1) Elevation of the latissimus dorsi
      muscle in the rat is a reliable and practical animal model for seroma formation;
      (2) Sequelae of clinically significant seromas are often as severe as skin flap
      necrosis; (3) An inflammatory reaction may be associated with seromas.

PMID- 8747290
TI  - Natural course of postsurgical adhesions.
AB  - To evaluate the natural course of postsurgical adhesion formation, a descriptive
      animal study was performed in a standardized rat adhesion model, involving the
      uterine horn and peritoneal side wall. Extent and type of postsurgical adhesion
      formation was evaluated at increasing postoperative time intervals up to 1 year,
      both through inter- and intra-animal observations (laparotomy and repeated
      laparotomy group). The extent of the adhesions was found to be similar while the
      type of the adhesions changed markedly, especially during the early observation
      periods. From day 1 until 1 month post- operatively, the adhesions became
      increasingly more organized and vascular and were separable with sharp dissection
      only. From the present study it was concluded that spontaneous lysis of
      postsurgical adhesions, once they are established, does not seem to occur. The
      most optimum time for surgical intervention when scheduled to lyse newly formed
      adhesions will be between 8 days and 1 month after the initial procedure.

PMID- 8747291
TI  - Advanced non-animal microsurgical exercises.
AB  - For the novice microsurgeon, suturing simple lines on a static model ill prepares
      them for the technically difficult live model that is to follow. A practice card
      was therefore designed to make the transition easier. The basic building block is
      rubber glove sutured to form a simple tube. From this point, progressive
      exercises are carried out. These are (1) simple suturing, (2) tube anastomosis,
      (3) end-to-end anastomosis, (4) end-to-side anastomosis, (5) side-to-side
      anastomosis, (6) inequality of diameters, and (7) free graft placement. Since the
      student is faced with problems that are challenging and progressively complex, a
      noticeable improvement is seen in their skills. These models introduce the
      student to planning and instrumentation that they would deal with in the clinical
      situation. Once the student has mastered these exercises, he/she is ready to
      advance to the rat model.

PMID- 8747292
TI  - Discriminating between Ixodes ticks by means of mitochondrial DNA sequences.
AB  - Ticks of the genus Ixodes have recently assumed prominence because they
      frequently serve as vectors of important zoonoses, including Lyme disease and
      babesiosis. The morphological characteristics that have been used in their
      identification often are ambiguous and are useful solely at a particular stage of
      development. Here we report the DNA sequence of the mitochondrially encoded 16S
      rRNA gene of nine different Ixodes ticks and an outgroup from another genus,
      Dermacentor. The sequences readily discriminate between these ticks. Samples of
      I. dammini from the northeastern and upper midwestern United States differ from
      southeastern I. scapularis at about 2% of the nucleotides. This difference is
      about half that separating other members of the I. ricinus group of species, but
      exceeds typical levels of intraspecific variation. Two major clades exist within
      the I. ricinus complex. One includes I. cookei, I. hexagonus, and I. angustus.
      The other includes I. persulcatus, I. pacificus, I. muris, I. ricinus, I.
      scapularis, and I. dammini. We conclude that mtDNA sequences are useful for
      unravelling the systematics of these important vectors of human disease.

PMID- 8747293
TI  - Phylogenetic analysis of Pacific salmon (genus Oncorhynchus) based on
      mitochondrial DNA sequence data.
AB  - Previous phylogenetic analyses of the fishes belonging to the genus Oncorhynchus
      based on mitochondrial DNA data have produced conflicting trees. This is
      especially true with respect to the relationships among the three most derived
      Pacific salmon species, the pink salmon (Oncorhynchus gorbuscha), sockeye salmon
      (Oncorhynchus nerka), and chum salmon (Oncorhynchus keta). Smith (Syst. Biol.
      41(1): 41-57, 1992) suggested that introgression in opposite directions on either
      side of the Pacific ocean may account for some of the conflicting data. The
      ATPase 6 and ND3 mitochondrial genes were sequenced from Asian and North American
      representatives of several species of Pacific salmon and the aligned sequences
      were analyzed along with other data on these genes. Analysis of the ATPase 6 and
      ND3 sequence data and RFLP data gives strong support for a sister relationship
      between pink salmon and chum salmon.

PMID- 8747294
TI  - Molecular phylogenetics of oryzomyine rodents: the genus Oligoryzomys.
AB  - Cytochrome b sequences (401 bp) were used to investigate the phylogenetic
      relationships of a group of South American rodents. The study focused on the
      tribe Oryzomyini (Family Muridae, Subfamily Sigmodontinae) and two of its genera,
      Oryzomys and Oligoryzomys, especially the latter. Genetic distances separating
      Oryzomys species average 19%, while those separating Oligoryzomys species are
      much smaller (mean 11%). When analyzed cladistically, cytochrome b sequences
      provide weak support for the monophyly of Oryzomyini, but strong evidence for
      paraphyly of Oryzomys. The cladogram supports the monophyly of Oligoryzomys;
      however, the branching pattern among its species suggests evolutionary
      relationships that conflict with hypotheses based on morphology and allozymes. In
      these taxa, sequences of nucleotides making up cytochrome b violate an important
      assumption of phylogenetic analysis, independence of characters. The implications
      of this finding are discussed for phylogeny reconstruction and the measurement of
      support for cladograms.

PMID- 8747295
TI  - MtDNA phylogeography of the California newt, Taricha torosa (Caudata,
      Salamandridae).
AB  - Thirty-six individuals of the California newt, Taricha torosa, representing 22
      populations from throughout the range of the two currently recognized subspecies,
      torosa and sierrae, were examined for sequence variation in a segment (375 bp) of
      the mitochondrial (mt) cytochrome b gene. The maximum sequence divergence within
      T. torosa is about 9%. Phylogenetic analyses used the sister taxa T. rivularis
      and T. granulosa as outgroups. Eighteen haploid sequence types found in T. torosa
      were grouped by parsimony, maximum likelihood, and neighbor-joining analyses into
      five mitochondrial clusters: two in torosa (the northern and southern clusters)
      and three in sierrae (the northern, central, and southern clusters). The southern
      sierrae cluster apparently shared a most recent common ancestor with the northern
      torosa cluster. The approximate time of sequence divergence within the current
      species was calibrated using the known fossil record (0.8% divergence per million
      years or 0.01 maximum likelihood distance per million years). Phylogenetic
      implications of mtDNA sequence variation for evolution and biogeography of the T.
      torosa species complex are discussed.

PMID- 8747296
TI  - A hierarchical molecular phylogeny within the genus Daphnia.
AB  - The nucleotide sequences of two mitochondrial DNA regions were used to determine
      phylogenetic relationships in the genus Daphnia (water fleas), a group for which
      systematics are historically unstable. A portion of the small ribosomal RNA was
      used to reconstruct higher-level relationships among species, while a portion of
      the more rapidly evolving control region was used to reconstruct lower-level
      relationships among populations. Two unexpected results were obtained. First, the
      subgeneric status of Ctenodaphnia falls into uncertainty on the basis of the
      failure of the 12S rRNA sequences to support these species as comprising an
      outgroup to the remainder of Daphnia species. Second, the high similarity of 12S
      rRNA sequences of Daphnia pulex and Daphnia pulicaria samples, coupled with the
      dual paraphyly of these samples as reconstructed from control-region analysis,
      suggests that they are two clonotype constellations within the same species
      complex. A combination of a variety of ecological influences has apparently
      resulted in the evolution of sets of Daphnia genotypes that are genetically
      cohesive despite their phenotypic divergence.

PMID- 8747297
TI  - Mhc-DRB genes and the origin of New World monkeys.
AB  - The major histocompatibility complex (Mhc) is a family of loci characterized by
      its relatively rapid evolutionary turnover, large genetic distances between
      genes, and long persistence of allelic lineages effected by balancing selection.
      These features render the Mhc highly suitable for answering questions concerning
      speciation and adaptive radiation. The aim of the present study was to use Mhc
      DRB genes to make inferences about the founding population of the Platyrrhini.
      Three segments, each approximately 300 base pairs in length, of the platyrrhine
      DRB genes were amplified by the polymerase chain reaction and sequenced. The
      segments were derived from intron 2, exon 3, and exon 6 of DRB genes from
      different species of New World monkeys. The results of the study have revealed
      that on a phylogenetic tree, all of the tested platyrrhine genes appear to form a
      single cluster, while all catarrhine DRB genes form a distinct cluster, although
      the bootstrap values fail to provide statistically significant support for the
      separation of these two clades. This observation suggests that the multiple
      platyrrhine genes originated from a single ancestral gene after the divergence of
      the Platyrrhini and Catarrhini and thus contradicts the results of an earlier
      study in which some exon 2 DRB sequences appeared to predate the split of the two
      primate groups. The inconsistency in the DRB gene phylogeny can be explained by
      postulating convergent evolution for the peptide-binding region of the DRB exon 2
      sequences. The phylogeny of the platyrrhine DRB genes (except for exon 2) is
      relatively "shallow"; the distances between genes are relatively short (in
      comparison to the catarrhine DRB genes), and there is a tendency for sequences of
      individual species to cluster together. The phylogeny of the platyrrhine DRB
      genes is consistent with the postulate that a small population founded the group
      and that there is an ongoing adaptive radiation from small, relatively isolated
      founding populations.

PMID- 8747298
TI  - Evolution of NADH dehydrogenase subunit 2 in east African cichlid fish.
AB  - The complete sequence (1047 bp) of the mitochondrially encoded ND2 gene was
      obtained from 31 species of cichlid fishes to investigate the evolutionary
      history of the species flocks of the East African lakes. The observed pattern of
      nucleotide substitution in this sequence is typical of mitochondrial genes,
      showing a high transition bias and rapid mutational saturation, especially at
      codon positions where base frequencies are unequal. The base composition of the
      third position of codons is heterogeneous among species, suggesting frequent
      shifts in the pattern of substitution. Phylogenetic analysis of the sequences
      shows that the mtDNA variation in Lake Malawi cichlids is nested monophyletically
      within the range of variation shown by Tanganyikan cichlids. The closest
      Tanganyikan relatives of the Malawi flock are members of the tribe Tropheini.
      Classifications based on morphology are generally supported by the mtDNA data,
      with some significant exceptions in the Tropheini and Lamprologini. Because of an
      apparently rapid radiation of the Tanganyikan lineages, it is difficult to assess
      the basal topology of the Tanganyikan radiation at this time. Divergences among
      tribes are consistent with an intralacustrine radiation within the past 10
      million years.

PMID- 8747299
TI  - Phylogenetic relationships of the Prodontria (Coleoptera; Scarabaeidae; subfamily
      Melolonthinae), derived from sequence variation in the mitochondrial cytochrome
      oxidase II gene.
AB  - The beetle genus Prodontria is of importance to New Zealand conservation
      programs. All Prodontria species are brachypterous (having reduced wings), and
      the genus presents some interesting evolutionary and biogeographic questions that
      are testable using phylogenetic reconstruction. A phylogeny was produced for 14
      flightless Prodontria species, 2 macropterous (fully winged) Odontria species,
      and single representatives of 2 outgroup genera using sequence data from the
      mitochondrial COII gene. The data support probable conspecificity of the
      morphologically similar P. modesta and P. bicolorata but do not support their
      hypothesized sister-species relationship with the geographically proximate P.
      lewisi. The alpine P. capito is found to be a paraphyletic group, with the most
      eastern population diverging after the western populations made their appearance.
      Many interesting biogeographic disjunctions are here proposed to be anomalous and
      the result of morphological convergence. The data do not support the idea of a
      common flightless ancester for Prodontria, but suggest that brachyptery has
      evolved numerous times. In some instances, this appears to have led to
      contemporaneous speciation resulting in little resolution of phylogenetic
      relationships in some parts of the tree. These data allow for a new
      interpretation of the origin and diversification of the southern New Zealand
      flightless melolonthine fauna. Multiple speciation events involving wing
      reduction are suggested to involve at least one widespread flighted ancestor that
      has given rise to brachypterous forms.

PMID- 8747300
TI  - Systematics of New World monkeys (Platyrrhini, Primates) based on 16S
      mitochondrial DNA sequences: a comparative analysis of different weighting
      methods in cladistic analysis.
AB  - In order to investigate the effects of different weighting methods on a phylogeny
      reconstruction based on DNA sequences and to evaluate the phylogenetic
      information content of various secondary structures, a fragment of the large
      ribosomal mitochondrial gene (16S) was sequenced from 13 species of New World
      monkeys, three species of catarrhines, and Tarsius. The data were analyzed
      cladistically without weighting characters or changes, and with different
      weighting methods: a priori differential weights for transitions and
      transversions, two variants of dynamic weighting for each kind and direction of
      change, and successive approximations, using both the character consistency index
      (CI) and the rescaled consistency index (RC). The results were compared with
      published trees constructed from nuclear sequences of E-globins and morphological
      characters by different authors. The result of the analysis of the mtDNA data set
      with successive approximations, using the RC as weighting function, was the
      closest to the topology on which all molecular and morphological trees concur.
      Other relationships were unique to this tree. "Loops" were the type of secondary
      structure that showed maximum variation in sequence length and sites with the
      lowest character CI and RC. A large number of sites within loops showed high
      values for these indices, however, which suggests that uniform downweighting of
      these regions represents a large loss of phylogenetic information. Successive
      weighting, which assigns a weight for each particular character, seems to be a
      desirable alternative to this practice. We propose a new variant of dynamic
      weighting, which we call homoplasy-correcting dynamic weighting, that like
      dynamic weighting, is applicable to any kind of sequence, coding or noncoding.

PMID- 8747301
TI  - Phylogenetic relationships inferred from the sequence and secondary structure of
      ITS1 rRNA in Albinaria and putative Isabellaria species (Gastropoda, Pulmonata,
      Clausiliidae).
AB  - An analysis of the ITS1 sequence variation among five species of terrestrial
      pulmonate snails was performed to decide between two conflicting hypotheses
      concerning the phylogeny of these anatomically similar gastropods. It turned out
      that the so-called genus Isabellaria is a polyphyletic entity; the diagnostic,
      apomorphic structure of its clausilial apparatus, enabling a nearly complete
      obstruction of the shell aperture with the animal at rest, apparently evolved
      more than once from ancestors currently classified with the speciose genus
      Albinaria. The classification based on general shell shape and sculpture, and
      distributional patterns, turns out to be the natural one. This study also
      provides the first data on ITS1 sequences in gastropods. The recently published
      ITS1 sequence of another molluscan species, a bivalve, is quite different but
      similar in length to that of the snails.

PMID- 8747302
TI  - Phylogenetic relationships among the true porpoises (Cetacea:Phocoenidae).
AB  - Portions of the cytochrome b gene and control region of the mitochondrial DNA
      molecule were sequenced to investigate systematic relationships among the six
      extant species of true porpoises, (Cetacea: Phocoenidae). Phylogenetic analyses
      of mitochondrial cytochrome b sequences support a close relationship between
      Burmeister's porpoise, Phocoena spinipinnis, and the vaquita, Phocoena sinus, and
      the association of these two species with the spectacled porpoise,
      Australophocaena dioptrica. The latter result is not in concordance with a recent
      morphological reclassification which groups A. dioptrica with Dall's porpoise,
      Phocoenoides dalli, in the subfamily Phocoenoidinae. The molecular analysis found
      no support for this grouping. A. dioptrica was originally described as a member
      of the genus Phocoena, and our results support returning it to that genus at this
      time. Finally, the data suggest that the tropical species Neophocaena
      phocaenoides, the finless porpoise, may represent the most basal member of the
      family. The control region sequences corroborated the relationships among the
      closely related taxa P. sinus, P. spinipinnis, and A. dioptrica, but were unable
      to resolve the deeper branches of the tree, probably as a result of a high level
      of saturation of these sequences.

PMID- 8747303
TI  - Brain natriuretic peptide in hypertension.
AB  - Brain natriuretic peptide (BNP) was first identified in the porcine brain and
      later isolated from porcine, rat, and human hearts. In humans, plasma BNP
      concentrations are progressively elevated with increasing severity of
      hypertension, particularly when left ventricular hypertrophy (LVH) is present.
      This presumably reflects increases in ventricular mass associated with increased
      synthesis and constitutive secretion of BNP from ventricular tissue. In this
      report, plasma BNP may be a marker for hypertensive LVH. Acute administration of
      BNP induces significant natriuresis and suppresses plasma aldosterone in
      hypertensive subjects. However, further studies are necessary to clarify the
      pathophysiological significance of BNP in essential hypertension.

PMID- 8747304
TI  - Altered L-DOPA systems for blood pressure regulation in the lower brainstem of
      spontaneously hypertensive rats.
AB  - Recent findings have enhanced our understanding of the roles played by the L-DOPA
      system in the baroreceptor reflex and in blood pressure regulation in the lower
      brainstem. L-DOPA is probably a neurotransmitter of primary baroreceptor
      afferents terminating in depressor sites of the nucleus tractus solitarii (NTS).
      It also seems to be a neurotransmitter in depressor sites of the caudal
      ventrolateral medulla (CVLM) and in pressor sites of the rostral ventrolateral
      medulla (RVLM) of normotensive Wistar rats. We have explored whether or not
      presynaptic and postsynaptic functions of the L-DOPA system in these areas are
      altered to maintain hypertension in adult spontaneously hypertensive rats, as
      compared with age-matched Wistar Kyoto rats. In this review article, we survey
      the roles of the L-DOPA system in the baroreceptor reflex and in blood pressure
      regulation in the rat lower brainstem.

PMID- 8747305
TI  - Angiotensin II-induced hypertension: effects on central and peripheral atrial
      natriuretic peptide.
AB  - Angiotensin (Ang) II and atrial natriuretic peptide (ANP) have opposing effects
      on blood pressure, sympathetic activity, vasopressin and ACTH secretion, salt
      appetite, and drinking. We observed their interaction by infusing Ang II (7.2
      nmol/h) into the peritoneum (i.p.) or into the lateral ventricle (i.c.v.) of rats
      with osmotic minipumps for seven days. At sacrifice, rats receiving Ang II-i.c.v.
      had a systolic blood pressure of 184 +/- 3 (SEM) mmHg, those receiving Ang II
      i.p. had 159 +/- 5 mmHg (p < 0.05), while controls had 109 +/- 2 and 110 +/- 2
      mmHg, respectively (p < 0.05). Drinking and urine volume increased similarly in
      rats receiving Ang II by either route, while Uosm decreased. Renin (PRA) values
      were lower (p < 0.05) in rats receiving Ang II-i.c.v. (0.7 +/- 0.2 ng Ang l/ml/h)
      or Ang II-i.p. (0.9 +/- 0.2) than in the respective controls (2.3 +/- 0.7 and 2.0
      +/- 0.3). Plasma ANP values with Ang II-i.c.v. (18 +/- 1.6 pg/ml) or with Ang II
      i.p. (49 +/- 6) were also lower (p < 0.05) than respective controls (89 +/- 12,
      76 +/- 4). Vasopressin (AVP) concentrations in the plasma were not influenced by
      the regimens. In the brain, the ANP contents in areas of the so-called AV3V
      region (organum vasculosum laminae terminalis, preoptic periventricular nucleus,
      medial preoptic nucleus) were similarly and significantly reduced by both Ang II
      i.c.v. and Ang II-i.p.. ANP values were also reduced in the median eminence by
      both types of Ang II-treatment, while ANP concentrations in the supraoptic
      nucleus were increased. The data show that Ang II infusions producing a chronic
      rise in blood pressure exert similar effects on drinking behavior, PRA, and ANP
      concentrations in blood and brain. The AV3V area may be pivotal to both models.

PMID- 8747306
TI  - Central GABAergic mechanisms are defective in salt-induced hypertension in
      borderline hypertensive rats.
AB  - We examined the role of central GABAergic mechanisms in salt-induced hypertension
      and exaggerated responses to stress in borderline hypertensive rats (BHR), the
      first offspring of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats
      (WKY). The studies were done in conscious BHR and WKY on high (H) (8% NaCl) or
      normal (N) (0.3% NaCl) salt diets for 5 weeks. A high-salt diet elevated arterial
      pressure (AP) (p < 0.01) and augmented pressor responses to shaker stress (p <
      0.05) in BHR but not in WKY. Intravenous hexamethonium caused a greater decrease
      in AP in BHR-H than in BHR-N at rest. Muscimol (a GABA agonist) injected into the
      central ventricle (i.c.v.) caused a greater decrease in resting AP (p < 0.01) and
      heart rate (HR) (p < 0.05) and BHR-H than in BHR-N. Renal sympathetic nerve
      activity (RSNA) did not change in BHR-H, but increased (p < 0.05) in BHR-N during
      muscimol-induced hypotension, although the magnitudes of muscimol-induced
      hypotension were greater in BHR-N than in BHR-N. The increases in RSNA in
      response to intravenous nitroglycerin were similar in BHR-N and BHR-N. Muscimol
      attenuated pressor and tachycardic responses to stress more in BHR-N than in BHR
      N (p < 0.01). Muscimol did not alter AP and HR at rest or their responses to
      stress in the two groups of WKY. The magnitudes of pressor response to
      bicuculline (a GABA antagonist) did not differ between the two groups of BHR.
      These results suggest that a high salt diet may alter the central GABAergic
      system in BHR, which contributes to salt-induced hypertension and augmented
      pressor and tachycardic responses to stress.

PMID- 8747307
TI  - The relationship between serum gamma-glutamyl transpeptidase levels and
      hypertension: common in drinkers and nondrinkers.
AB  - A significant association between elevations of serum gamma-glutamyl
      transpeptidase (gamma-GTP) levels and those of blood pressure and hypertension
      has been reported separately in drinkers and nondrinkers. The aim of the present
      study is to evaluate whether the relationship between serum gamma-GTP and the
      prevalence of hypertension is the same or similar in both drinkers and
      nondrinkers. The study subjects comprised 4,920 male nondrinkers, 9,390 male
      daily drinkers, 8,081 female nondrinkers, and 278 female daily drinkers, who were
      aged 40 to 59 years. The prevalence of hypertension in the male and female daily
      drinkers was 1.5 and 1.3 times, respectively, higher than in the nondrinkers.
      Mean systolic blood pressure in the male and female drinkers was 4.4 and 3.1
      mmHg, respectively, higher than in the nondrinkers. After adjusting for age, body
      mass index, and serum gamma-GTP levels, the differences in the prevalence of
      hypertension and the mean systolic blood pressure level between the drinkers and
      nondrinkers decreased to 1.2 times and 2.7 mmHg, respectively. Although these
      small differences remained statistically significant, the association between
      serum gamma-GTP and hypertension appears to be quite similar in both drinkers and
      nondrinkers, suggesting that hepatic steatosis may play a common, pathogenetic
      role in the development of hypertension.

PMID- 8747308
TI  - Comparison of first-line antihypertensive drugs by a randomized cross-over method
      -a preliminary report.
AB  - The present study was undertaken to compare the effects of first-line
      antihypertensive drugs in Japanese patients. Four antihypertensive drugs were
      studied: trichlormethiazide (TCT), nifedipine retard (NIF), atenolol (ATN), and
      enalapril malate (ENP). Thirty-eight patients (16 men and 22 women; age, 53.3 +/-
      8.8 years, mean +/- SD) were enrolled in the study. After a control period of 2
      to 4 weeks, the four drugs were administered according to a randomized, cross
      over design, the duration of each treatment period being 8 to 12 weeks. The
      initial dose of each drug was increased until blood pressure (BP) fell to less
      than 150/90 mmHg. The maximum doses of TCT, NIF, ATN, and ENP were 4, 40, 50, and
      20 mg/day, respectively. The protocol was completed in 25 of the 38 patients. The
      BPs (SBP/DBP) at the end of each period were 168 +/- 3 (mean +/- SEM)/105 +/- 1
      (control), 149 +/- 4/ 98 +/- 2 (TCT), 138 +/- 3/89 +/- 2 (NIF), 151 +/- 4/94 +/-
      2 (ATN), and 152 +/- 4/97 +/- 2 mmHg (ENP). The BP during NIF treatment was
      significantly lower than during the other treatments. This finding suggests that
      the calcium antagonist had a greater hypotensive effect than the other first-line
      antihypertensive drugs studied. The subjects seem to more closely resemble black
      rather than white populations with respect to their response to antihypertensive
      treatment.

PMID- 8747309
TI  - Influence of aging on insulin sensitivity in essential hypertensives and
      normotensives.
AB  - Insulin resistance and hyperinsulinemia have been linked with essential
      hypertension. Age-associated increases in glucose intolerance and hypertension
      are also well established. To clarify the influence of aging on the insulin
      sensitivity, euglycemic hyperinsulinemic glucose clamp technique was carried out
      in 41 normotensive subjects and 42 patients with essential hypertension. The
      subjects of these groups were divided into two subgroups: young (< 40 years old)
      and middle-elderly (> or = 40 years old). Insulin sensitivity was assessed as M
      value, the rate at which glucose must be infused to maintain a basal blood
      glucose level. In normotensive subjects, the young subgroup had a significantly
      higher M-value than did the middle-elderly subgroup. There was a significant
      negative correlation between age and M-value in normotensive subjects. On the
      other hand, there was no significant difference in M-value between the young and
      middle-elderly subgroups in the patients with essential hypertension. The age did
      not correlate with M-value in the hypertensive group. The normotensive subjects
      showed a significantly lower M-value than the hypertensive patients in the young
      group, but not in the middle-elderly group. These results indicate that 1)
      insulin sensitivity declines with age in normotensive subjects and that 2)
      insulin sensitivity is already diminished in the early stage of hypertension, and
      no further decrease in insulin sensitivity occurs with aging in essential
      hypertensive patients.

PMID- 8747310
TI  - Reduced natriuretic response to increased renal interstitial hydrostatic pressure
      in Dahl salt-sensitive rats during volume expansion.
AB  - Renal interstitial hydrostatic pressure (RIHP) plays a key role in the link
      between renal hemodynamics and the rate of the tubular reabsorption of sodium and
      water. Our objective was to determine whether the natriuretic response to a rise
      in RIHP induced by acute saline infusion would be altered in prehypertensive,
      Dahl salt-sensitive (DS) rats. We compared the effects of an acute saline load
      (2.5 ml/100 g BW over 30-min) on RIHP and urinary sodium excretion in Dahl salt
      resistant (DR) (n = 11) and DS rats (n = 11) maintained from birth on a low
      sodium diet. Baseline mean arterial pressure, glomerular filtration rate rate,
      and urinary sodium excretion did not differ between DR and prehypertensive DS
      rats. Urine flow rate and urinary sodium excretion increased significantly in
      both groups following saline loading. Increases were significantly (p < 0.05)
      less in the prehypertensive DS rats (0.32 +/- 0.07 to 3.62 +/- 0.79 microEq/min)
      than in the DR rats (0.71 +/- 0.22 to 6.30 +/- 1.35 microEq/min). RIHP also
      increased significantly in both groups, but did not differ significantly in DR
      (7.3 +/- 1.1 to 9.7 +/- 1.7 mmHg) vs. DS rate (7.9 +/- 1.0 to 9.8 +/- 1.3 mmHg).
      At an equal mean arterial pressure, DS rats showed a reduced natriuretic capacity
      after an acute saline load, prior to the development of hypertension. Renal
      tubular sensitivity to the increased RIHP that was induced by an acute saline
      load was blunted in prehypertensive DS rats.

PMID- 8747311
TI  - Mechanism of hypertension induced by chronic inhibition of nitric oxide in rats.
AB  - In order to clarify the mechanism of hypertension induced by a nitric oxide (NO)
      synthase inhibitor, L-NG-nitro-L-arginine (LNNA), metabolites of NO,
      catecholamines, and hemodynamic parameters were measured during 7 days of oral
      administration of LNNA in rats. Control rats received either L-arginine (L-Arg)
      or the vehicle. systolic blood pressure, measured by the tall-cuff method was
      elevated throughout the period of LNNA administration, but that in the two
      control groups was not influenced by treatment. Heart rate decreased on the
      second day only in LNNA-treated rats. Although L-Arg treatment had no influence,
      LNNA markedly decreased the plasma level and the urinary excretion of nitrate
      ions (NO-3). Urinary excretion of noradrenaline was significantly decreased on
      the second day of LNNA administration and returned to the control level
      thereafter. When hemodynamic changes were measured by using radioactive
      microspheres, LNNA was found to increase blood pressure by markedly increasing
      total peripheral resistance. Cardiac output was decreased by LNNA. L-Arg, again,
      did not influence the hemodynamic variables as compared with the vehicle control
      group. The regional vascular resistance index was increased by LNNA in many
      tissues and organs, except the brain and the heart. Regional blood flow, on the
      other hand, was significantly decreased only in the liver and skin by LNNA. The
      marked reduction in NO3- in urine by LNNA-treatments may indicate that the
      measured NO3- is exclusively of endogenous origin, and that inhibition of NO
      production causes elevation of blood pressure by constricting peripheral
      arteries. Sympatholytic responses by the baroreceptor reflex were thereby evident
      only on the second and the third days, which was indicated by bradycardia and
      suppression of noradrenaline excretion into urine. These results indicate that
      the inhibition of NO synthase actually decreases production of endogenous NO, and
      that the hypertension caused by decreases in NO production is due to elevation of
      total peripheral vascular resistance.

PMID- 8747312
TI  - Update on urticaria and angioedema (hives).
AB  - The update on urticaria involves new concepts on the pathogenesis and the
      treatment of severe hives that are unresponsive to conventional treatments. A
      newly described autoantibody IgG against IgE receptor has been identified in some
      severe chronic urticaria patients. Anti-inflammatory and immunomodulating agents
      are being used with increasing frequency by academic faculty and other physicians
      in severe chronic idiopathic urticaria (CIU).

PMID- 8747313
TI  - Adverse reactions associated with skin testing and immunotherapy.
AB  - Fatalities have been associated with allergen skin testing and immunotherapy.
      Therefore, physicians using such tests and therapy should be knowledgeable in
      their use and take proper precautions to decrease the risk of anaphylaxis. The
      American Academy of Allergy and Immunology recommends a 20-minute wait that can
      be extended for high risk patients following an injection, and that the physician
      in charge of administering immunotherapy should be familiar with and prepared to
      appropriately treat anaphylaxis. Future treatment with peptides rather than whole
      allergens may increase safety.

PMID- 8747314
TI  - The role of immunotherapy in allergic rhinitis/allergic asthma.

PMID- 8747315
TI  - Implications of practice parameters (guidelines).
AB  - Practice parameters (guidelines) have been developed for many years. The first
      such parameter, developed by a Joint Task Force of the American Academy of
      Allergy and Immunology, and the American College of Allergy and Immunology, was
      on the diagnosis and treatment of patients with asthma. It was sent in notebook
      form to members of the Academy and College in 1993. An updated version will be
      published as a supplement to the Journal of Allergy and Clinical Immunology
      sometime in 1995. Although the overriding consideration in the development of
      these parameters is to improve the level of care for patients, and by doing so to
      decrease asthma morbidity and mortality, recent guidelines have also emphasized
      cost factors, especially those that are now being developed by managed care
      organizations. Practice parameters can also reduce malpractice liability, and
      studies have even shown a reduction in hospital admissions by instituting
      relatively simple measures of patient behavior. There is no doubt that practice
      parameters will become an important part of our everyday life.

PMID- 8747316
TI  - Allergists, antitrust, and managed care.

PMID- 8747317
TI  - Atopy and skin reactivity at school age in children followed up from birth, with
      special reference to atopy prevention in infancy and atopic findings at preschool
      age.

PMID- 8747318
TI  - Chu I-Hai, Prince of Lu (1618-1662) last regent of the Chinese Ming dynasty.

PMID- 8747319
TI  - John Locke (1632-1704) British physician and philosopher.

PMID- 8747320
TI  - Nicolas Boileaux-Despreaux (1636-1711) French poet, author, and literary critic.

PMID- 8747321
TI  - Sir John Floyer (1649-1734) British physician and pioneer clinical investigator.

PMID- 8747322
TI  - William III (1650-1702) Prince of Orange and King of England, Scotland, and
      Ireland.

PMID- 8747323
TI  - Survival during frozen and subsequent refrigerated storage of Lactobacillus
      acidophilus cells as influenced by the growth phase.
AB  - Cells of Lactobacillus acidophilus propagated in peptonized milk nutrient broth
      maintained at pH 5 were harvested during the late logarithmic (log) phase and at
      6 h into the stationary phase of growth. Concentrated cultures were prepared from
      each age of cells, frozen, and stored at -196 degrees C. The concentrated
      cultures were assayed for numbers of total and bile-tolerant lactobacilli, beta
      galactosidase activity, and ability to assimilate cholesterol before and after
      storage at -196 degrees C. Nonfermented acidophilus milk, prepared following 28 d
      of storage at -196 degrees C from each concentrated culture, was tested before
      and after 0, 7, 14, 21, and 28 d of storage at 7 degrees C. No decrease in
      numbers of total or bile-tolerant lactobacilli, beta-galactosidase activity, or
      amount of cholesterol assimilated was observed for any of three strains studied
      during storage at -196 degrees C. There were no significant differences between
      the two harvest times during storage at this temperature for any of the three
      strains. However, when the cells were suspended in milk and stored at 7 degrees
      C, the numbers of total and bile-tolerant lactobacilli declined over time as did
      the beta-galactosidase activity and the ability to assimilate cholesterol. The
      cells from L. acidophilus 223, harvested 6 h into the stationary phase, exhibited
      significantly less decrease in total numbers during extended storage at 7 degrees
      C than did the cells harvested in the late logarithmic phase. There was little or
      no difference in the decline in numbers of total lactobacilli between the two
      harvest times for strains 606 and 107. All strains decreased significantly in
      beta-galactosidase activity and the ability to assimilate cholesterol during
      storage in milk at 7 degrees C with no significant differences between the two
      harvest times.

PMID- 8747324
TI  - Susceptibility of beta-lactoglobulin and sodium caseinate to proteolysis by
      pepsin and trypsin.
AB  - The susceptibility of beta-LG and sodium caseinate to proteolysis by pepsin and
      trypsin was investigated using SDS or urea-PAGE. The effects were studied of
      heat, urea, and 2-mercaptoethanol on proteolysis. Native beta-LG was resistant to
      hydrolysis by pepsin or trypsin because of its compact globular structure. Heat
      treatment of beta-LG solutions at 90 to 100 degrees C for 5 or 10 min caused
      changes in the structure or conformation of the protein that rendered it
      accessible to pepsin and enhanced the extent of proteolysis by trypsin. The
      susceptibility of beta-LG to proteolysis by pepsin was markedly increased in the
      presence of urea (3 to 6 M), and the effect was reversible after removal of urea
      by dialysis. Proteolysis by trypsin was also increased by the presence of 2% 2
      mercaptoethanol. Sodium caseinate was very accessible to pepsin without
      pretreatment and was extensively hydrolyzed at pH 1 to 5 in the presence of 5 M
      urea (which prevented the protein from precipitation in the isoelectric region);
      optimal pH was about 2. The activity of pepsin on sodium caseinate at pH 2 was
      not significantly affected by urea concentration up to about 8 M. The results
      indicated that the changes in conformation and structure of beta-LG that were
      induced by heating, reduction, or urea rendered the protein susceptible to peptic
      hydrolysis.

PMID- 8747325
TI  - Preparation of apolactoferrin with a very low iron saturation.
AB  - Iron(III) removal from lactoferrin by an iron(III)-chelating resin with
      immobilized 3-hydroxy-2-methyl-4(1H)-pyridinone ligands was studied at
      physiological pH in the presence of citrate. The resin had a marked effect on the
      extent of iron removal. By using the iron(III)-chelating resin, removal of iron
      from lactoferrin was nearly complete in < 24 h. Apolactoferrin with 4% iron
      saturation could be prepared conveniently from 100% or from 18% iron-saturated
      lactoferrin under mild conditions without affecting the iron-binding capacity of
      the protein. The iron saturation of the obtained apolactoferrin was much lower
      than that of the apolactoferrin prepared by reported methods.

PMID- 8747326
TI  - Survey of the conjugated linoleic acid contents of dairy products.
AB  - The objective of this research was to determine the content of conjugated
      linoleic acid, an anticarcinogen, in dairy products. Fifteen cheeses, three
      fermented dairy products (other than cheeses), and four fluid milk products (two
      brands for each product) were included in the survey. Total lipids, fatty acids,
      protein, moisture, and titratable acidity were also measured to determine the
      relationship between the content of these constituents and conjugated linoleic
      acid content. The conjugated linoleic acid content of cheeses ranged from 3.59 to
      7.96 mg/g of lipid. Blue, Brie, Edam, and Swiss cheeses had significantly higher
      conjugated linoleic acid content than the other cheeses. Sharp Cheddar cheeses
      tended to have higher conjugated linoleic acid content than the medium Cheddar
      cheeses, but the increase was not significant. The conjugated linoleic acid
      content of the other fermented dairy products ranged from 3.82 to 4.66 mg/g of
      lipid, and cultured buttermilk had the highest content. The conjugated linoleic
      acid contents of four fluid milks ranged from 3.38 to 6.39 mg/g of lipid and were
      not significantly different from one another. Multiple linear regressions of
      conjugated linoleic acid content and the total fatty acid content indicated a
      relationship between conjugated linoleic acid content and the content of
      precursors and intermediates of conjugated linoleic acid formation, including
      linoleic and oleic acids.

PMID- 8747327
TI  - Environmental streptococcal intramammary infections of the bovine mammary gland.
AB  - Characteristics of environmental streptococcal IMI were investigated over a 7-yr
      period for a herd in total confinement. A total of 374 new environmental
      streptococcal IMI was detected. Approximately 50.5% of IMI were new in the dry
      period, and 49.5% were new in lactation. The rate of new IMI was .00312 IMI/cow
      day during the dry period and .00054 IMI/cow day during lactation. The
      percentages of cows and quarters with an environmental streptococcal IMI present
      at calving were 10.6 and 3.2%, respectively. The percentage of heifers with an
      environmental streptococcal IMI at calving was similar to that for cows. The rate
      of new environmental streptococcal IMI was greater during the 1st mo of lactation
      than during the remainder of lactation. The rate of IMI during late lactation was
      higher for older cows than for either heifers or cows in second lactation. The
      rate of environmental streptococcal IMI during the dry period and during
      lactation was greatest during summer. The mean days of lactation that cows were
      infected for all IMI was 12.3 d. Approximately 41% of IMI had a duration of < 8
      d. Stage of lactation, season of the year, and parity influenced the rate of new
      IMI.

PMID- 8747328
TI  - Influence of mastitis on D-amino acid content of milk.
AB  - The California Mastitis Test was used as an indicator of mastitis in this study.
      Five cows were chosen for each of the five test scores (from 0 = healthy to 4 =
      severe mastitis). Milk samples were analyzed for free AA and free D-AA. The
      contents of free AA, free D-AA, and the ratio of free D-AA to free AA increased
      significantly as the California Mastitis Test score increased. The free D-AA
      content of foremilk (first milk jets) from healthy cows (test score = 0) was
      approximately five times that in samples drawn later from the same udders.
      Contents of free AA and free D-AA were highly associated with test score and
      udder inflammation. Very low concentrations of free D-AA are normal for raw milk.
      Higher concentrations of free D-AA could be attributed to inclusion of foremilk
      and milk from cows having subclinical mastitis in the bulk tank milk.

PMID- 8747329
TI  - Distribution of annexins I, II, and IV in bovine mammary gland.
AB  - Annexins belong to a family of proteins that are characterized by their ability
      to bind phospholipids in a Ca(2+)-dependent manner that is thought to be involved
      in a variety of biological processes. The present study determined the
      localization of annexins in subcellular fractions, nuclei in particular, of cow
      mammary gland by immunoblot analysis using monoclonal antibodies to annexins I,
      II, IV, and VI. The analysis revealed that annexins I, II, and IV were present in
      cytosol, but VI was not. Annexins I and IV were found in the nuclear fraction,
      but annexin II was only faintly present. Annexin VI was also undetectable in this
      fraction. Cytosolic annexin I had a molecular mass of 36 kDa. The 36-kDa annexin
      I was also found in the nuclear fraction. A 38-kDa annexin I was additionally
      detected in nuclei. The cytosolic and nuclear 36-kDa annexin I and the nuclear 38
      kDa annexin I showed different isoelectric points, as revealed by two-dimensional
      PAGE. Annexin IV from cytosolic and nuclear fractions had similar molecular
      masses and isoelectric points.

PMID- 8747330
TI  - Milk fever and dietary cation-anion balance effects on concentration of vitamin D
      receptor in tissue of periparturient dairy cows.
AB  - Milk fever is the clinical disease associated with severe hypocalcemia in dairy
      cows. In this experiment, we tested the hypothesis that calcium homeostasis is a
      result of a decreased concentration of receptors for 1,25-dihydroxyvitamin D in
      the tissues of cows that develop milk fever. Samples of colon mucosa were
      obtained for analysis of vitamin D receptor concentration in a longitudinal study
      of Jersey cows during the 2 wk before and after parturition. In the first study,
      21 cows fed an alfalfa hay diet were biopsied every 3rd d from 2 wk before to 2
      wk after calving. The concentration of vitamin D receptor in the colon during
      late gestation was three- to fourfold higher than the concentration of vitamin D
      receptor in the colon mucosa in nonpregnant cows (90 +/- 8 vs. 26 +/- 5 fmol/mg
      of protein). At parturition, colon concentration of vitamin D receptor decreased
      to 66 +/- 7.5 fmol/mg of protein. During early lactation, concentrations of
      vitamin D receptor in the colon were similar to precalving concentrations. There
      was no significant difference of concentrations of vitamin D receptor in the
      colon prior to calving, at calving, or in early lactation between cows that did
      develop milk fever and those that did not. Results were similar in a second
      study, in which 7 cows were fed a high cation alfalfa diet, and 6 cows were fed
      the same diet with anionic salts added. Those data do not support the hypothesis
      that decreased concentrations of vitamin D receptor prior to calving is a
      causative factor of milk fever within the Jersey breed. However, a decline of
      concentrations of vitamin D receptor in tissue at calving may reduce the ability
      of all cows to respond to the calcium demands of lactation.

PMID- 8747331
TI  - Effect of abomasal infusion of saliva on reticular motility and ruminal liquid
      contents of steers.
AB  - Two Holstein and two Jersey steers with ruminal and abomasal cannulas were used
      in a 4 x 4 Latin square experiment to test the effects of abomasal infusion of
      saliva on reticular contractions and on contents of the reticulorumen. Steers
      were fed a ration based on sorghum silage (58.3% DM) at 2-h intervals in 12 equal
      amounts at 1.25 times the maintenance requirement. Saliva was collected from
      eight esophageally fistulated steers, pooled, and stored frozen at -20 degrees C.
      Saliva was mixed with McDougall's buffer (0, 33.3, 66.7, or 100% saliva) and
      infused abomasally at a rate of 1.5 L/h for 3 h. Abomasal infusion of saliva
      resulted in linear decreases in ruminal liquid and DM contents. Ruminal dilution
      rate tended to be faster for infused steers as concentration of saliva increased.
      Frequency of reticular contractions increased linearly as saliva infusion
      increased. The influence of saliva infusion on duration of reticular contractions
      was complicated by inverse patterns of response for each separate phase of the
      reticular contraction. The first phase of the contraction was influenced by
      saliva infusion in a negative, quadratic manner; the second phase exhibited an
      opposite response pattern. A quadratic effect was evident for both amplitude and
      area of contractions, indicating that the contraction strength was decreased at
      the intermediate salivary infusion. Postruminal passage of saliva may influence
      ruminal digestive function by regulating reticular motility and digesta passage.

PMID- 8747332
TI  - The prediction of methane production of Holstein cows by several equations.
AB  - Ruminants are one of many sources contributing to atmospheric methane. The
      accuracy of seven published equations for methane prediction was evaluated using
      a data file consisting of 16 experiments (602 observations). Methane energy
      emissions ranged from .89 to 7.21 Mcal/d for Holstein cows. The DMI ranged from
      9.7 to 28.7 kg/d for lactating cows and 4.0 to 12.9 kg/d for nonlactating cows.
      Mean dietary concentrations of ADF, CP, and ether extract were similar for
      lactating and nonlactating cows (20.9, 16.5, and 3.0% for lactating cows versus
      21.2, 15.7, and 2.9% for nonlactating cows, respectively). Milk production ranged
      from 2.7 to 55.9 kg/d. Prediction equations were ranked by correlation
      coefficients and error of prediction. Prediction of methane energy loss from
      lactating and nonlactating Holstein cows with equations based on the daily total
      intake or intake of digested cellulose, hemicellulose, and nonfiber carbohydrates
      (OM - NDF - CP - ether extract) provided the highest correlation coefficients for
      reproducibility and the lowest errors of prediction. Predictions were poor for
      lactating cows when a quadratic function of DMI was used. In general, equations
      estimated methane production more accurately and precisely for nonlactating than
      for lactating cows.

PMID- 8747333
TI  - Juice-extracted grass pellets and sodium bicarbonate for cows fed timothy silage
      of two chop lengths.
AB  - Eighteen multiparous Holstein cows in midlactation were used in a switchback
      design trial to evaluate the effect of chop length (3 or 30 mm) of timothy grass
      silage, containing less than 30% ADF and treated with formic acid, on DMI and cow
      performance. Within chop length, addition of NaHCO3 (2% of DMI) or the
      replacement of 30% of silage DM with juice-extracted grass pellets was also
      evaluated. Cows were fed a TMR composed of 90% silage and 10% concentrate. Silage
      preservation characteristics were not different between chop lengths. The DMI and
      apparent digestibility were similar among treatments. Yields of 4% FCM (24.9 vs.
      22.7 kg/d), fat (1.03 vs. .93 kg/d), and protein (.83 vs .77 kg/d) were higher
      with the short chopped silage. Milk protein, milk NPN content, and serum urea
      were higher for cows fed long chopped silage. Yields of milk and milk
      constituents were not affected by the addition of juice-extracted grass pellets
      or NaHCO3. Fat percentage and fatty acid composition of milk remained unchanged
      by treatments. Reduction of particle size, from 30 to 3 mm, of timothy grass,
      treated with formic acid at harvest and using compaction at ensiling in bag
      silos, did not affect silage conservation characteristics but did improve milk,
      fat, and protein yields when cows were fed high silage diets.

PMID- 8747334
TI  - Responses in urea and true protein of milk to different protein feeding schemes
      for dairy cows.
AB  - Four multiparous Holstein cows were used in a 4 x 4 Latin square to investigate
      the effects of protein concentration, degradability, and quality on plasma urea
      concentration and milk N constituents. Diets varied in the amount and proportion
      of RDP and RUP relative to NRC requirements: diet 1, excessive RDP, deficient
      RUP; diets 2 and 3, balanced for RDP and RUP; and diet 4, excessive RDP, balanced
      for RUP. Diet 3 was formulated for optimal AA balance as predicted by the Cornell
      Net Carbohydrate and Protein System. Diets contained 34% corn silage, 19% alfalfa
      haylage, and 49% concentrate (DM basis). Concentrates varied in amounts of urea
      and soybean, corn gluten, and fish and blood meals. Concentrations of urea N and
      NPN in milk varied among diets: diet 1, 19 and 34 mg/dl; diet 2, 16 and 31 mg/dl;
      diet 3, 15 and 30 mg/dl; and diet 4, 23 and 39 mg/dl, respectively. Increases in
      NPN concentration were attributed to increases in the urea fraction of NPN.
      Intake of RUP and AA balance influenced milk true protein content; diet 1, 2.89%;
      diet 2, 2.90%; diet 3, 3.01%; and diet 4, 2.95%. the proportions of true protein
      and urea in milk are influenced by CP concentration, protein type, and protein
      quality.

PMID- 8747335
TI  - Effects of rumen-inert fat on lactation, reproduction, and health of high
      producing Holstein herds.
AB  - Two hundred twenty of 443 cows freshening between June 1989 and March 1990 in
      five commercial Holstein herds were fed .45 kg/d of rumen-inert fat from calving
      until 200 DIM. Control diets were fed as TMR and contained, on average, 3.7 to
      4.8% supplemental fat (DM basis). Test herds had rolling herd averages of 9300 to
      13,250 kg of milk. Production of 4% FCM and milk increased 1.01 (3.3%) and 1.50
      kg/d (4.6%), respectively, for primiparous cows fed additional fat. Multiparous
      cows from four herds demonstrated no response; multiparous cows in one herd
      increased production of 4% FCM by 2.88 kg/d (8.2%), milk by 2.45 kg/d (6.4%), and
      milk fat by .14kg/d (10.6%) in response to additional fat. An explanation of
      response differences among herd for multiparous cows was not possible. For
      primiparous and multiparous cows, increased genetic potential increased treatment
      response. Increased body condition score at calving influenced treatment response
      of multiparous cows. Thinner cows produced more milk and less milk fat in
      response to additional dietary fat than did fatter cows. Most reproductive
      indices were unaffected by treatment. Cows receiving additional fat had lower,
      but nonsignificantly lower, incidences of most health disorders. Responses to
      rumen-inert fat by cows receiving high concentrations of dietary fat were
      marginal and were affected by body condition score at calving and by genetic
      potential.

PMID- 8747336
TI  - Duodenal infusion of oil in midlactation cows. 7. Interaction with niacin on
      responses to glucose, insulin, and beta-agonist challenges.
AB  - Metabolic effects of rapeseed oil, niacin, or both were investigated for
      multiparous Holstein-Friesian cows in midlactation. Cows were continuously
      infused with water (control), rapeseed oil, niacin, or rapeseed oil plus niacin
      into the proximal duodenum, using a 4 x 4 Latin square design. Oil infusion
      resulted in higher plasma concentrations of cholesterol and urea, but a lower
      plasma concentration of glucose, without changing basal concentrations of
      insulin, NEFA, and BHBA in plasma or causing a difference in the concentration of
      metabolites in jugular versus mammary vein plasma. Effects of niacin were small
      and nonsignificant for almost all of these measurements. Responses of plasma
      glucose, NEFA, and insulin to challenges by isoproterenol (beta-agonist),
      glucose, or insulin were studied. Rapeseed oil infusion lowered glucose
      tolerance. Niacin infusion increased responses by glucose and insulin to glucose
      challenge. Oil and niacin negatively interacted for responses of plasma
      concentrations of glucose and insulin to isoproterenol challenge. Positive energy
      balance in midlactation cows possibly masked potential niacin effects of the
      studied measurements.

PMID- 8747337
TI  - Management factors related to Salmonella shedding by dairy heifers.
AB  - In a national survey of dairy operations with > or = 30 milking cows, fecal
      samples from 6861 preweaned dairy heifer calves on 1063 operations were tested
      for Salmonella. One hundred forty-five (2.1%) of the fecal samples from 79 (7.4%)
      of the farms tested positive for Salmonella. A multivariate logistic regression
      model revealed that medicated milk replacer and hay fed to dairy heifers from 24
      h of age until weaning were associated with a reduced risk of Salmonella
      sheddings, as was calving in an individual animal area within a building.

PMID- 8747338
TI  - Associations of the epithelial mucin, PAS-1, with yield, health, and reproductive
      traits in Holstein dairy cows.
AB  - Five polymorphic forms of the epithelial mucin, PAS-1, were identified in milk by
      SDS-PAGE. The sizes of PAS-1 ranged from 194.5 to 163 kDa. Mature equivalent
      milk, fat, and protein yields and protein and fat percentages from 139 cows in
      The Pennsylvania State University herd were analyzed with two models. Both models
      contained a year and season combination of calving and parent average. In Model
      [1], yields were regressed on the mean size of PAS-1 either linearly or linearly
      and quadratically. Model [2] included PAS-2 phenotype as a discrete variable.
      Lactation mean of somatic cell scores (119 cows), number of times bred (136
      cows), and days open (136 cows) were analyzed with the same two models excluding
      parent average (data not available). Mean size of PAS-1 was not linearly related
      to the traits evaluated. The effects of PAS-1 phenotypes as a discrete variable
      were significant for mature equivalent fat and protein yields, fat percentage,
      number of times bred, number of times bred restricted to 3, and days open
      restricted to 150 d. Overall, there was little indication of an important linear
      or quadratic relationship between PAS-1 size and traits measured.

PMID- 8747339
TI  - Efficacy of barrier-type postmilking teat germicides against intramammary
      infection.
AB  - Two barrier teat dips were evaluated for efficacy in preventing new IMI by
      Staphylococcus aureus and Streptococcus agalactiae during experimental exposure
      trials, and two barrier dips were evaluated during natural exposure trials.
      Dipping in an experimental product containing nicin as a germicide using
      experimental exposure demonstrated no difference in rate of new Staph. aureus IMI
      (10.2%) compared with that of controls (7.1%) or in the rate of new Strep.
      agalactiae IMI (13.6%) compared with that of controls (11%). Testing of an
      experimental .55% chlorhexidine gluconate barrier dip using experimental exposure
      resulted in an increased rate of new Staph. aureus IMI compared with that of
      controls (4.8 vs. 1.7%, respectively), but no difference in the rate of new
      Strep. agalactiae IMI in dipped quarters (6.1%) compared with that of controls
      (3.3%). Dipping with a commercial .3% iodine barrier dip during natural exposure
      increased the number of new coagulase-negative staphylococcal and total IMI by
      56.6 and 30.6%, respectively, compared with a 1% iodophor dip without barrier.
      Use of an experimental .3% iodine barrier dip during natural exposure
      demonstrated no difference in total rate of new IMI (18.4%) compared with that of
      controls (20.3%); however, after germicide concentration was increased to .5%
      iodine and further tested, the reformulated product reduced new IMI by 43.1%.
      Under the conditions of these trials, the barrier teat dips tested were no more
      efficacious than no teat dip or using a nonbarrier product.

PMID- 8747340
TI  - Efficacy of a barrier teat dip containing .55% chlorhexidine for prevention of
      bovine mastitis.
AB  - A natural exposure trial was conducted for 12 mo in a commercial herd of 125
      lactating cows to compare the efficacy of an experimental barrier teat dip
      containing .55% chlorhexidine gluconate with the efficacy of a 1% iodophor for
      preventing new IMI and clinical mastitis. Teats of half of the cows were dipped
      in the experimental barrier product, and teats of the remaining half of the herd
      were dipped in the 1% iodophor product. Quarters dipped with the experimental
      barrier product had fewer new IMI caused by Escherichia coli, coagulase-negative
      staphylococci, or Gram-positive bacilli than did quarters dipped in the 1%
      iodophor. Incidence of new IMI caused by Serratia spp. and Pseudomonas spp. was
      greater for quarters dipped in the experimental barrier product than for quarters
      dipped in the 1% iodophor. Efficacy of the two teat dips against new IMI caused
      by Staphylococcus aureus, environmental streptococci, and Klebsiella spp. did not
      differ. Incidence of bacteriologically negative clinical cases of mastitis was
      greater in quarters dipped in the 1% iodophor than in quarters dipped in the
      experimental barrier product. Incidence of clinical mastitis cases caused by
      Staph. aureus, environmental streptococci, E. coli, Klebsiella spp., Serratia
      spp., and Pseudomonas spp. did not differ between treatment groups.

PMID- 8747341
TI  - Selection of a mathematical model to generate lactation curves using daily milk
      yields of Holstein cows.
AB  - Mathematical descriptions of early stages of lactation were investigated using
      daily milk yields of 117 first, 78 second, 57 third, and 36 fourth lactations of
      120 Holstein cows fitted by 10 models. The measure of fit was the error mean
      squares, which were replaced by ranks to perform an analysis of variance with
      lactation number, model, and period as factors and with cows as replicates. The
      interaction of model and lactation number was significant for the fit of the
      entire lactation. A significant interaction of model and period was obtained for
      the fit of three 30-d intervals. For the entire lactation, the best fit for all
      four lactations occurred from the diphasic logistic function, y = d1(1
      tanh2(b1(nk-c1))) + d2(1-tanh2(b2(n-c2))). For the first 30 d, a modified gamma
      function gave the best fit for the first lactation, the inverse polynomial
      function for the second lactation, and the quadratic log function for the third
      lactation. The diphasic logistic function gave the best fit for the remaining two
      periods and was not significantly different from the best fitting models for the
      first 30-d period. Hence, this function may be useful to describe the lactation
      curve of Holstein cows for dairy herds in which the daily milk yield of
      individual cows is constantly monitored with a computer.

PMID- 8747342
TI  - Novel products and new technologies for use of a familiar carbohydrate, milk
      lactose.
AB  - The cheese industry produces large amounts of lactose in the form of cheese whey
      and whey permeate, generating approximately 27 million tonnes/yr in the US alone.
      Many uses have been found for whey and lactose, including uses in infant formula;
      bakery, dairy, and confectionery products; animal feed; and feedstocks for
      lactose derivatives and several industrial fermentations. Lactose use in food
      products, however, is somewhat limited because of its low solubility and
      indigestibility in many individuals. For this reason, lactose is often hydrolyzed
      before use. Still, demand is insufficient to use all available whey lactose. The
      result is a low market value for lactose; almost half of the whey produced each
      year remains unused and is a significant waste disposal problem. Several
      approaches are possible for transforming lactose into value-added products. For
      example, galactooligosaccharides can be produce through enzymatic treatments of
      lactose and may be used as a probiotic food ingredient. Organic acids or xanthan
      gum may be produced via whey fermentation, and the fermented whey product can be
      used as a food ingredient with special functionality. This paper reviews the
      physical characteristics, production techniques, and current uses of lactose,
      whey, and lactose derivatives. Also examined are novel fermentation and
      separation technologies developed in our laboratory for the production of
      lactate, propionate, acetate, and xanthan gum from whey.

PMID- 8747343
TI  - Functional properties and applications of edible films made of milk proteins.
AB  - Edible films and coatings based on milk proteins have been developed to be used
      as a protective layer on foods or between food components. The most important
      functionalities of an edible film or coating include control of mass transfers,
      mechanical protection, and sensory appeal. Control of mass transfers involves
      preventing foods from desiccation, regulating microenvironments of gases around
      foods, and controlling migration of ingredients and additives in the food
      systems. Adequate mechanical strength of an edible film is necessary to protect
      the integrity of packaging throughout distribution. The sensory properties of an
      edible coating or film are a key factor for acceptance of final products. Simple
      milk protein films are good barriers to gas transfers because of their complex
      intermolecular bindings. Lipid is frequently incorporated into protein films to
      improve their properties as barriers to moisture vapor. Protein films are
      distinctly different in mechanical profiles from those films made of other
      materials. Approaches traditionally used in material sciences have been adapted
      and modified for studying the functionality of edible films. Potential uses of
      innovative processing technologies in film making to alter the film functionality
      are briefly discussed. A survey of potential applications of edible film based on
      milk protein is presented.

PMID- 8747344
TI  - Commercial utilization of minor milk components in the health and food
      industries.
AB  - Whey has gained a great deal of respectability in the US during the past 5 to 10
      yr as an ingredient in many food and dairy products. However, its value as a
      resource for many medically active components is not recognized in this country
      as it is in Japan and Europe. This paper reviews the minor components in whey and
      the potential for commercial application. Individual whey components of
      significance include alpha-lactalbumin, beta-lactoglobulin, bovine serum albumin,
      immunoglobulins, lactoferrin, and lactoperoxidase. Whey is also a good resource
      for lactose and lactose derivatives such as lactulose, lactitol, and
      oligosaccharides. Other minor milk components of biological significance include
      milk salts and components related to casein. Many of these components exhibit
      biological activity that is valuable in nutraceuticals or antimicrobials.
      Commercial utilization in the US is compared with that of other countries.

PMID- 8747345
TI  - Management of Perthes' disease.

PMID- 8747346
TI  - Early diagnosis and treatment of hinge abduction in Legg-Perthes disease.
AB  - A review of 106 cases of Legg-Perthes disease disclosed 26 in whom a particularly
      poor radiographic appearance was seen. Hinge abduction was detected in 19 of
      these patients and was suspected but not proven in the remainder. Hinge abduction
      was found to occur early in the course of Legg-Perthes, and hinging frequently
      occurred about an unossified portion of femoral head, making detection difficult.
      Failure of movement of the lateral corner of the epiphysis under the edge of the
      acetabulum on an internally rotated and abducted radiograph is prima facie
      evidence of hinge abduction. Confirmation is easily obtained by arthrography.
      Hinging must be relieved if guidance of femoral head growth by the healthy
      acetabulum is to be possible. Both clinical and radiographic outcomes were worse
      in patients with unrelieved hinge abduction. Relief of hinging can frequently be
      accomplished by traction, and containment can then be maintained by appropriate
      surgery.

PMID- 8747347
TI  - Combination trochanteric arrest and intertrochanteric osteotomy for Perthes'
      disease.
AB  - A significant complication associated with femoral varus osteotomy (FVO) is
      trochanteric overgrowth and concomitant abductor weakness. We identified 28
      patients who underwent unilateral FVO for Perthes' disease, had a healed femoral
      head on their latest radiograph, and had at least 2.1 years of follow-up. The
      patients were divided into two groups; group 1: patients who did not receive
      prophylactic trochanteric arrest (TA) at the time of FVO; group 2: patients who
      did receive TA. Clinical parameters were quantified using objective measurements
      and a scoring system for reported symptoms. At postoperative follow-up, group 2
      had greater articulotrochanteric distance (ATD), better range of motion, less
      abductor weakness, less pain, and superior activity levels. These differences
      were statistically significant. This study demonstrates that when properly
      performed with respect to indications and timing, the combination of TA and FVO
      provides an effective means of managing Perthes' disease when "head at risk"
      signs are present. The authors include a detailed discussion of surgical
      technique.

PMID- 8747348
TI  - Chondrolysis and the stiff hip in Perthes' disease: an immunological study.
AB  - The study was undertaken to determine whether immunologic mechanisms could
      account for hip stiffness and chondrolysis in Perthes' disease. Histologic and
      electron microscopic evidence of perivascular collections of plasma cells and
      lymphocytes in synovial tissue and the demonstration of elevated levels of
      circulating immunoglobulins in children with Perthes' disease suggest that
      immunologic processes are involved. Chondrolysis was observed only in children
      who were > 10 years old, with a totally avascular epiphysis in the stage of
      fragmentation. Because the serum immunoglobulin levels were not dependent on age,
      extent of epiphyseal avascularity, and the degree of hip stiffness, monitoring of
      these levels is unlikely to be of help in predicting chondrolysis.

PMID- 8747349
TI  - Perthes' disease after "irritable hip": delayed bone age shows the hip is a
      "marked man".
AB  - We report 13 children, aged 4 through 8 years, who were seen with a prolonged or
      recurrent irritable hip syndrome. Only those with > 2 years' delay in their bone
      age eventually declared themselves to have been in the early phase of Perthes'
      disease at initial examination when the original hip radiographs had been normal.
      A plain wrist radiograph was found to be a useful screening tool to differentiate
      those who should have early repeat investigation such as radiographs, or
      preferably a magnetic resonance image scan if available, to detect the disease in
      its initial phase. This facilitated early regular imaging to assess femoral head
      shape and so permitted early treatment before deformity had occurred in those
      with whole-head involvement.

PMID- 8747350
TI  - The effect of arthrocentesis in transient synovitis of the hip in the child: a
      longitudinal sonographic study.
AB  - Twenty-one children with transient synovitis of the hip were treated in two
      consecutive groups. In 12 patients aspiration of the synovial effusion was
      performed within 24 h of admission. In a second group of nine patients no
      aspiration was performed. There was no other difference in treatment. Joint
      effusion was studied sonographically in comparison with the nonsymptomatic
      contralateral hip. Sonography was performed immediately after admission, within
      12 h after aspiration, and repeatedly during a follow-up period of up to 15 days.
      Following aspiration the capsular distention decreased to 49% but recurred within
      24 h to 72% of the preoperative value. However, during the first 4 days of follow
      up the capsular distention in the aspirated cases was significantly and
      permanently lower than in the nonaspirated cases. We conclude that arthrocentesis
      in the acute stage of transient synovitis of the hip in the child permanently
      reduces the intracapsular effusion.

PMID- 8747351
TI  - Intermediate follow-up of a simple method of hip arthrodesis in adolescent
      patients.
AB  - Thirteen male patients (average age, 15.6 years) underwent intraarticular hip
      arthrodesis for unilateral disabling hip disease. Follow-up averaged 6.6 years.
      Seven patients had excellent or good Harris hip scores. Ten patients had low back
      pain, and seven patients had knee pain on the side of the fused hip. Limb-length
      discrepancy averaged 3.7 cm. A progressive hip adduction drift (average, 7
      degrees) occurred during follow-up. Patients whose hips were fused in a position
      of 20-25 degrees flexion and whose limb-length discrepancies were < 2 cm had
      significantly lower incidences of back pain. Cybex muscle testing revealed
      significantly decreased quadriceps strength (29%) on the hip-fusion side. Gait
      laboratory analysis demonstrated decreased velocity, stride length, and cadence.
      There were two mildly symptomatic nonunions. Based on these results, we recommend
      that the hip fusion be positioned in 20 degrees flexion and 0 degree abduction.
      The joint must be completely debrided down to viable bone to maximize chances for
      union. Maintaining a limb-length discrepancy of < 2 cm is essential to minimize
      the incidence of low back pain, quadriceps deficiency, and abnormal gait
      parameters.

PMID- 8747352
TI  - Open bone peg epiphysiodesis for slipped capital femoral epiphysis.
AB  - The records of 43 patients who underwent 64 open bone peg epiphysiodeses for
      slipped capital femoral epiphysis were retrospectively reviewed. There were 18
      unstable and 46 stable slips. The average duration of follow-up was 35 months
      (range, 12-100). Healing occurred in all cases at an average of 17 weeks after
      surgery. At the time of healing, 27 hips (42%) showed a change in the degree of
      slip. At the most recent visit, the head-shaft angle had improved in 19 hips
      (30%), although the majority of hips showed resorption of the anterior neck
      prominence. The degree of remodeling showed no correlation with time to healing,
      duration of follow-up, or the status of the triradiate cartilage. The average
      operating time and blood loss per hip were 122 +/- 34 min and 426 +/- 238 ml,
      respectively. Complications included four hips with avascular necrosis and three
      with chondrolysis, three infections, four delayed wound healings, seven cases of
      transient anterolateral thigh hypesthesia, and 44 hips with hetertopic
      ossification. Because of the potential morbidity of this procedure, we no longer
      perform it as a primary operation for stable slipped capital femoral epiphysis.

PMID- 8747353
TI  - Pin removal in slipped capital femoral epiphysis: the unsuitability of titanium
      devices.
AB  - In an effort to predict which slipped capital femoral epiphysis fixation devices
      might cause fewer retrieval problems, 27 consecutive implant-retrieval procedures
      were reviewed, and mechanical tests using many currently available devices were
      performed. Problems occurred with both stainless steel and titanium devices if
      implanted for > 1 year. This tendency for increased problems was statistically
      significant for the titanium group, and analysis of a retrieved titanium screw
      showed evidence of osseointegration (direct bone-metal contact at > 90% of the
      interface) using backscattered image scanning electron microscopic analysis.
      These clinical data and data from mechanical testing suggest that stainless steel
      screws or trocar-tipped Steinmann pins are better suited for fixation of slipped
      capital femoral epiphysis.

PMID- 8747354
TI  - Fixation of slipped capital femoral epiphyses with unthreaded 2-mm wires.
AB  - Twenty chronic and three acute-on-chronic slipped capital femoral epiphyses
      (SCFEs) were fixed with unthreaded 2-mm wires. Nineteen hips were fixed with
      three wires, and four with four wires. Postoperatively, patients bore full weight
      after 6 weeks. There were no pin penetrations or cases of chondrolysis. No
      femoral heads grew off the wires. Fifteen hips showed no change in the head-shaft
      angle postoperatively. Of the remaining eight, two improved their head-shaft
      angles in the anteroposterior (AP) view (6,7 degrees), and five improved in the
      lateral view (6-13 degrees, average, 11 degrees). Two hips worsened in the AP
      view (9,10 degrees), and none in the lateral view.

PMID- 8747355
TI  - Percutaneous in situ fixation of slipped capital femoral epiphysis using two
      threaded Steinmann pins.
AB  - Twenty-six patients with 34 slipped capital femoral epiphyses were treated by
      percutaneous in situ pinning with two 5/32-inch threaded Steinmann pins. Twenty
      three patients with 31 hips were followed-up until the time of epiphyseal closure
      and pin removal. The average time to closure was 8.5 months (range, 3-25). The
      average operative time for pinning was 53 min (range, 18-115). The average
      operative time for pin removal was 42 min (range, 12-132). Complications included
      two progressive slips, two poorly placed pins, one pin breakage during removal,
      and one case of capital necrosis. This technique is a quick, efficient means of
      stabilizing the slipped capital femoral epiphysis, with case of hardware removal.

PMID- 8747357
TI  - Central compartment pressure monitoring following clubfoot release.
AB  - Thirty-nine clubfeet undergoing primary soft tissue release for idiopathic
      clubfoot deformity had intrinsic compartment pressure monitoring for 36 h after
      surgery. This was done to determine whether pressures might be elevated to
      levels, and for durations, such that an intrinsic compartment syndrome might
      develop. Two groups were identified: in group 1 (23 feet) pressures were never
      elevated to > 20 mm Hg; in group 2 (16 feet) pressures > 30 mm Hg for a duration
      of at least 12 h were found. In a subgroup of group 2 (4 of 16 feet), pressures
      were > 50 mm Hg for at least 12 h. There was no statistical correlation between
      pressure recordings and surgeon, tourniquet time, severity of deformity, extent
      of release, and type of cast used. Thus 40% of feet are at risk of developing
      pressures that could cause an intrinsic compartment syndrome.

PMID- 8747356
TI  - The histopathology of injury to the accessory malleolar ossification center.
AB  - The evaluation of a traumatic lower limb amputation specimen revealed an
      incomplete fracture between the main and accessory malleolar ossification
      centers. This was not associated with extensive subperiosteal or intraarticular
      bleeding. This pattern of injury, without any displacement or completion to an
      unstable fracture, should be considered in a patient with specific tenderness
      over a malleolus after a twisting injury or direct blow to the ankle.

PMID- 8747358
TI  - Clinical and radiographic appearance of congenital talipes equinovarus after
      successful nonoperative treatment.
AB  - Thirty-one children with 49 feet after successful nonoperative treatment for
      congenital talipes equinovarus (CTEV) by redressements, hypoallergic adhesive
      bands, and plaster casts underwent follow-up. At the follow-up, the patients
      ranged in age from 4.2 years to 12.3 years (average, 8.3 years). The initial type
      of the deformity was as follows: type I (mild), 18 feet; type II (intermediate),
      29 feet; type III (severe), two feet. Mild supination of the forefoot in five
      feet, isolated excavation in three, and adduction greater than physiological in
      two feet were the only persistent elements of the deformity. The lack or
      restriction of the dorsal flexion in the ankle were noted in 22 feet. In only
      three feet was the Beatson-Pearson index was < 40 degrees. In 17 feet, the
      radiographs revealed full talonavicular reduction in sagittal and horizontal
      planes. The average value of the talometatarsal first and tibiocalcaneal angles
      as in accordance with the standard. The most characteristic osseous disturbances
      concerned the tarsal navicular (22 feet) and consisted of the decrease of the
      ossification center, its flattening, fragmentation, cystic-like changes, and
      wedging.

PMID- 8747359
TI  - Unilateral duplication of the great toe with anterolateral tibial bowing.
AB  - A syndrome consisting of unilateral duplication of the great toe in association
      with anterolateral bowing of the tibia is described. Patients with this syndrome
      have significant pedal difficulties after surgical management, but the tibial
      bowing spontaneously resolves without treatment. Tibial shortening is noted
      relative to the fibula. Associated clinodactyly and dysharmonic maturation of
      carpals and metacarpals are also seen. Current data are most consistent with a
      developmental rather than a genetic etiology.

PMID- 8747360
TI  - Osseous overgrowth after amputation in adolescents and children.
AB  - We retrospectively studied the incidence of primary surgical revision for stump
      overgrowth in a population of childhood and adolescent amputees. The anatomic
      location and the etiology of amputation are critical to the occurrence of
      overgrowth needing revision. Metaphyseal-level amputations are the most likely to
      develop overgrowth requiring revision (50%), whereas diaphyseal amputations are
      slightly less likely (45%). Joint disarticulations never develop overgrowth.
      Traumatic amputations are the most frequent mode of injury requiring revision of
      overgrowth (43%), followed by congenital or intrauterine amputations (30%) and
      elective amputations (20%). Radiographic classification of the osseous overgrowth
      helps define its severity and degree of ossific progression. Surgical revisions
      are usually performed when overgrowth reaches a grade 3 classification. The
      majority of skeletally immature diaphyseal- or metaphyseal-level amputees,
      including those with certain preexisting orthopaedic conditions, retain the
      ability to develop osseous overgrowth at the apex of the stump skeleton.

PMID- 8747361
TI  - Brown's procedure for congenital absence of the tibia revisited.
AB  - The results of reconstructive surgery in tibial hemimelia using a modified
      fibular transfer procedure as described by Brown were reviewed. A modified
      Brown's procedure was carried out on five patients with a total of seven affected
      limbs. A Syme's-type amputation of the foot was carried out in each case. All of
      the knees had quadriceps function preoperatively, which was considered a
      prerequisite for surgery. Average length of follow-up was 7 years, with a range
      of 2-12 years. The average age at time of surgery was 12.7 months, with a range
      of 7-26 months. At the time of review, all patients had reasonably good function
      of their lower extremities. All were ambulating with patellar tendon-bearing
      prostheses and thigh extensions for collateral support. The average arc of motion
      at review was 57.4 degrees, with further passive motion possible in all cases.
      Average extension was -18.5 degrees, and the average active flexion was 76
      degrees. We found that a fibular centralization procedure in a patient with at
      least grade III+ quadriceps function can give good functional results that do not
      appear to deteriorate over time.

PMID- 8747362
TI  - Perinatal limb ischemia: orthopaedic implications.
AB  - Fifteen patients (16 ischemic limbs) who ultimately required amputation for
      perinatal limb ischemia were treated at The Children's Hospital of Philadelphia
      and the Shriners Hospital for Crippled Children in Philadelphia between 1980 and
      1993. The average birth weight of these patients was 1,870 g, and the average
      gestational age was 30.8 weeks. Ischemic events occurred at an average postnatal
      age of 5.4 weeks. The causes of the ischemia included (a) arterial thrombosis as
      a complication of arterial catheterization (eight patients), (b) thromboembolism
      resulting from a hypercoagulable state (five patients), (c) intravenous
      infiltrate (one patient), and (d) in utero arterial thrombosis (one patient).
      Amputation was required at an average postnatal age of 8.5 weeks. The final
      patient, with concurrent ischemia involving the right hand and left leg, had
      complete resolution of the ischemic hand with fibrinolytic therapy alone and
      required only an amputation of the lower extremity. Eleven of the 15 patients
      were available for follow-up (two dead, two lost to follow-up), at an average of
      4.5 years. Nine of these 11 patients (six lower and three upper extremities) are
      functioning well in prostheses. The two remaining patients are infants who will
      be fitted for lower-extremity prostheses when they begin to attempt to walk.

PMID- 8747363
TI  - Variation of Baumann's angle with age, sex, and side: implications for its use in
      radiological monitoring of supracondylar fracture of the humerus in children.
AB  - We examined 577 elbow radiographs of children aged 2-14 years attending an
      accident and emergency department prospectively over a 2-year period, and after
      excluding 7% with an effusion, fracture, or oblique view, we calculated Baumann's
      angle on the remainder. We grouped the radiographs by age, sex, and side, giving
      52 groups with a minimum of 10 radiographs in each group. Baumann's angle was
      found to range from 64-82 degrees, mean 73.6 +/- 2 SD = 8.73 in boys; 69-81, mean
      75.6 +/- 2 SD = 5.78 in girls; 64-82, mean 73.5 +/- 2 SD = 5.78 on the left; and
      66-82, mean 73.7 +/- 2 SD = 7.47 on the right. Analysis of variance showed there
      was no significant difference in the mean comparing boys with girls at each age,
      left to right at each age in the boys or girls, and there was no increasing or
      decreasing trend over the years in either sex on each side.

PMID- 8747364
TI  - Vascular injuries and their sequelae in pediatric supracondylar humeral
      fractures: toward a goal of prevention.
AB  - Between 1988 and 1994, 128 consecutive children with grade III supracondylar
      humeral fractures presented for treatment at our hospital. Seventeen had absent
      or diminished (detected with Doppler but not palpable) radial pulses on initial
      examination. Fourteen of these 17 children recovered pulse (palpable) after
      reduction and stabilization of their fractures. The remaining three had
      persistent absence of radial pulse. Each of these three children was explored
      immediately and found to have a significant vascular injury requiring repair. Two
      of the 14 children who had initially regained their pulses had a progressive
      postoperative deterioration in their circulatory status during the first 24-36 h,
      including loss of the radial pulse. Both of these children had arteriograms that
      identified vascular injuries. Both underwent exploration and bypass grafting. One
      of these two children had been transferred 48 h after injury, resulting in delay
      of management of his vascular impairment. Despite exploration, vascular repair,
      and fasciotomy, he ultimately developed Volkmann's ischemic contracture. All five
      children with significant vascular injuries had absent or diminished radial
      pulses on presentation. Immediate reduction and fixation followed by careful
      evaluation and treatment of ischemia were associated with excellent outcome in
      four of the five children.

PMID- 8747365
TI  - A selective treatment approach to supracondylar fracture of the humerus in
      children.
AB  - The results of a "selective treatment" policy applied to 176 patients presenting
      with supracondylar fracture of the humerus are analyzed. As initial treatment 148
      patients underwent closed reduction and casting, seven closed reduction and
      pinning, 17 olecranon traction, and four open reduction and pinning. Analysis of
      patients by fracture type and initial treatment demonstrated a satisfactory
      outcome in 46 of 75 type III fractures and in 37 of 48 patients with type II
      fractures treated by closed reduction and casting. Thus a policy of initially
      pinning all such type III fractures in our unit would mean that 61% of such
      fractures would be pinned needlessly. Of type II fractures 77% would be
      needlessly pinned if such a policy was applied to type II fractures. The current
      trend towards pinning of all type III supracondylar fractures is not supported by
      the data from this study.

PMID- 8747366
TI  - Direct reduction with indirect fixation of distal tibial physeal fractures: a
      report of a technique.
AB  - Displaced intraarticular fractures of the distal tibia in children often require
      open reduction and internal fixation. Displaced epiphyseal fractures in the
      sagittal plane may be difficult directly to visualize from a standard medial
      malleolar incision, so accurate reduction may be impossible. Approaching the
      ankle joint by anterior arthrotomy, the fracture line can be directly visualized
      and accurately manipulated and reduced. However, access to the medial malleolus
      for insertion of internal fixation devices may be difficult from an anterior
      incision. We have found that after anterior arthrotomy and open reduction, rigid
      fixation can be placed percutaneously from medially or, in exceptional cases,
      from laterally under fluoroscopic control. The physis and talocrural joint can be
      seen and avoided in the growing child. Thirteen cases fixed by this method are
      reported. At 12.2-month average follow-up, clinical results were excellent. There
      were no instances of joint degenerative changes but one growth derangement.

PMID- 8747367
TI  - Distal tibial triplane fractures: long-term follow-up.
AB  - The cases of 35 patients in whom a triplane fracture had been treated at the
      Ramon y Cajal Hospital were reviewed. The diagnosis of biplane and triplane
      fracture can now be made by standard radiograph. However, plain radiographs alone
      did not accurately demonstrate the configuration of the fracture, and computed
      tomography must be performed. Closed reduction should be attempted first. Failure
      to obtain or maintain (or both) an adequate closed reduction is an indication for
      operative treatment. Prognosis is surprisingly good. Only when adequate reduction
      (< 2 mm displacement) has not been achieved can degenerative changes be seen at
      long-term follow-up (> 5 years).

PMID- 8747368
TI  - An arthroscopic technique for the reduction and fixation of tibial-eminence
      fractures.
AB  - A technique of arthroscopic reduction and fixation of type III tibial-eminence
      fractures is described. After reduction of the fracture, polyglactin (Vicryl)
      suture was passed into the knee with the use of the arthroscope to fix the
      fracture. Early mobilization of the patients was begun after 2 weeks. Two
      patients (aged 10 and 13 years old), with 2 years follow-up after treatment of
      their fracture with this technique, had full range of motion of the knee with no
      sign of instability. Arthroscopic reduction and fixation of type III tibial
      eminence fractures is a technique that can reduce hospital stay, rehabilitation,
      and the morbidity associated with the use of an arthrotomy for treatment.

PMID- 8747369
TI  - Distal femoral extension osteotomy for knee flexion contracture in patients with
      arthrogryposis.
AB  - Severe knee flexion contractures in patients with arthrogryposis multiplex
      congenita were treated by distal femoral extension osteotomy. Thirty-two
      operations were followed for an average of 32 months. Contractures were corrected
      from 49 degrees to 6 degrees. During follow-up there was a loss of correction of
      22 degrees at a rate of 0.9 degrees/ month. The angle of the distal femoral
      physis and the shaft of the femur was 2 degrees of flexion preoperatively, and
      postoperatively it measured 43 degrees of extension and at late follow-up it
      measured 19 degrees. Remodeling occurred at a rate of 1.0 degrees/month, which
      correlated with recurrence. All patients increased their ambulatory ability at
      least one level. There was one wound infection. Distal femoral extension
      osteotomy is effective and safe for the correction of knee flexion contracture.
      Recurrence occurs in all growing children.

PMID- 8747370
TI  - Medial-approach open reduction of hip dislocation in amyoplasia-type
      arthrogryposis.
AB  - In 95 children with amyoplasia-type arthrogryposis multiplex congenita, 40 hip
      dislocations in 26 patients were found. In 16 of these 26 patients, bilateral
      (nine patients) and unilateral (seven patients) dislocations were reduced by a
      medial-approach open reduction. The mean age at the time of surgery was 8.9
      months. Acetabular development was satisfactory. Complications included one early
      redislocation, two hips with stiffness, and four of 25 hips with avascular
      necrosis (types 1 and 2). Overall 80% (five of seven unilateral, 15 of 18
      bilateral hips) were rated good and 12% fair, and 8% (one of seven unilateral,
      one of 18 bilateral) were poor. Stiffness or asymmetry was not observed in the
      nine bilateral cases. This study suggests that dislocations in infants with
      amyoplasia may be successfully reduced by medial-approach open reduction.
      Bilateral reduction and concurrent correction of other lower limb contractures
      may be accomplished during the same surgical session.

PMID- 8747371
TI  - "Electromyographic and nerve conduction changes after tibial lengthening by the
      Ilizarov method".

PMID- 8747372
TI  - Strategies for phase II cancer chemoprevention trials: cervix, endometrium, and
      ovary.
AB  - Well-designed and conducted Phase II clinical trials are very important to cancer
      chemoprevention drug development. Three critical aspects govern the design and
      conduct of these trials--well-characterized agents, suitable cohorts, and
      reliable biomarkers for measuring efficacy that can serve as surrogate endpoints
      for cancer incidence. Requirements for the agent are experimental or
      epidemiological data showing chemopreventive efficacy, safety on chronic
      administration, and a mechanistic rationale for the chemopreventive activity
      observed. Agents that meet these criteria for chemoprevention of cervical cancer
      include antiproliferative drugs (e.g., 2-difluoromethylornithine), retinoids,
      folic acid, antioxidant vitamins and other agents that prevent cellular oxidative
      damage. Because of the significant cervical cancer risk associated with human
      papilloma virus (HPV) infection, agents that interfere with the activity of HPV
      products may also prove to be effective chemopreventives. In endometrium,
      unopposed estrogen exposure has been associated with cancer incidence. Thus, pure
      antiestrogens and progestins may be chemopreventive in this tissue. Ovarian
      cancer risk is correlated to ovulation frequency; therefore, oral contraceptives
      are potentially chemopreventive in the ovary. Recent clinical observations also
      suggest that retinoids, particularly all-trans-N-4-hydroxyphenylretinamide, may
      be chemopreventive in this tissue. The cohort should be suitable for measuring
      the chemopreventive activity of the agent and the intermediate biomarkers chosen.
      In the cervix, patients with cervical intraepithelial neoplasia (CIN) and in
      endometrium, patients with atypical hyperplasia, fit these criteria. Defining a
      cohort for a Phase II trial in the ovary is more difficult. This tissue is less
      accessible for biopsy; consequently, the presence of precancerous lesions is more
      difficult to confirm. The criteria for biomarkers are that they fit expected
      biological mechanisms (i.e., differential expression in normal and high-risk
      tissue, on or closely linked to the causal pathway for the cancer, modulated by
      chemopreventive agents, and short latency compared with cancer), may be assayed
      reliably and quantitatively, measured easily, and correlate to decrease cancer
      incidence. They must occur in sufficient incidence to allow their biological and
      statistical evaluation relevant to cancer. Since carcinogenesis is a multipath
      process, single biomarkers are difficult to validate as surrogate endpoints,
      perhaps appearing on only one or a few of the many possible causal pathways.
      Panels of biomarkers, particularly those representing the range of carcinogenesis
      pathways, may prove more useful as surrogate endpoints. It is important to avoid
      solely on biomarkers that do not describe cancer but represent isolated events
      that may or may not be on the causal pathway or otherwise associated with
      carcinogenesis. These include markers of normal cellular processes that may be
      increased or expressed during carcinogenesis. Chemoprevention trials should be
      designed to evaluate fully the two or three biomarkers that appear to be the best
      models of the cancer. Additional biomarkers should be considered only if they can
      be analyzed efficiently and the sample size allows more important biomarkers to
      be evaluated completely. Two types of biomarkers that stand out regarding their
      high correlation to cancer and their ability to be quantified are measures of
      intraepithelial neoplasia and indicators of cellular proliferation. Measurements
      made by computer-assisted image analysis that are potentially useful as surrogate
      endpoint biomarkers include nuclear polymorphism comprising nuclear size, shape
      (roundness), and texture (DNA distribution patterns); nucleolar size and number
      of nucleoli/nuclei; DNA ploidy, and proliferation biomarkers such as S-phase
      fraction and PCNA...

PMID- 8747373
TI  - Role of the pathologist in biomarker studies.
AB  - Cancer chemoprevention is defined as intervention by chemical agents prior to
      invasion to inhibit or slow the carcinogenic process. Using surrogate endpoint
      biomarkers in chemoprevention studies may reduce the size, length and cost of
      clinical prospective randomized trials in high-risk populations. Intermediate
      biomarkers are measurable alterations in the tissues at risk and include
      differentiation, genetic composition, biochemical expression, and proliferation.
      Assessment is possible because invasive epithelial neoplasms are known to begin
      as intraepithelial proliferations with a spectrum of cellular abnormalities
      extending to carcinoma in situ. Genetic heterogeneity begins in the
      intraepithelial phase; a stochastic accumulation of genetic errors characterizes
      the progression of clonal evolution within the tumor through the process of
      invasion and metastasis. Pathologic features associated with this process include
      tumor classification as well as whether it is intraepithelial or invasive. If the
      process is intraepithelial, the grade and extent of the intraepithelial lesion
      are reported. If the neoplasm is invasive, tumor size, extent, degree of
      differentiation (histologic and nuclear grade), mitotic rate, vascular invasion,
      and lymph node involvement are evaluated. In assessing biomarkers relevant
      chemoprevention, and without complete regression of the neoplasm with the
      chemopreventive agent or agents, measurable parameters along with histopathologic
      features are applicable. Three methods readily applicable for this purpose that
      can be applied to paraffin-embedded, formalin-fixed tissue include quantitative
      pathology, immunohistochemistry, and molecular biologic applications. These
      methods require some consistency in handling and processing the tissues under
      study; results may deteriorate due to a number of processing variables, including
      time to fixation, time in fixative, and fixative type. Quantitative pathology,
      including static image analysis and flow cytometry, can determine total DNA
      content. Using static image analysis, very small tumors can be studied. In
      addition, adjacent intraepithelial and invasive components of a tumor may be
      studied from a single slide. Steroid receptors, oncogenes, and other proteins
      detectable through immunohistochemical or molecular biologic methods can be
      quantitated by this technique as well. Cell cycle synthetic function is assayable
      by both methods. Flow cytometry can calculate the total percentage of cells in S
      phase, or the tumor cell S-phase fraction based on the percentage of cells
      detected between the G0, G1 peak and the G2 + M peak. A similar approach is
      generally not applicable with current image analysis equipment; however, cell
      cycle related proteins such as MIB-1 (Ki-67 associated) can be quantified.
      Immunohistochemical methods can employ a wide variety of monoclonal antibodies to
      detect oncogene related proteins, including HER-2/neu (c-erbB-2) and p53.
      Molecular biologic methods, including in situ hybridization, polymerase chain
      reaction, and in situ PCR, can have many applications when applied to paraffin
      embedded tissues, including detection of viral DNA, identification and
      measurement of apoptosis, and defining gene deletions.

PMID- 8747374
TI  - A phase II chemoprevention trial design to identify surrogate endpoint biomarkers
      in breast cancer.
AB  - Surrogate biomarkers for risk assessment and efficacy of potential
      chemopreventive agents are needed to improve the efficiency and reduce the cost
      of conducting chemoprevention trials. In addition to criteria of sensitivity,
      specificity, quantifiability, and reproducibility applicable to most potential
      biomarkers, there are additional specific constraints in developing biomarkers
      for specific organ sites. In the case of breast tissue, these difficulties
      include lack of a consensus on the nature of premalignant lesions and the
      histologic criteria used to define them; even when such a consensus can be
      evolved, there are limitations in visualizing such lesions without invasive
      biopsies. Also, knowledge of specific genetic and biochemical changes in
      premalignant lesions is limited. In addition, the physiology of breast tissue is
      cyclic, no proven, relevant markers can be studied in a randomly obtained needle
      aspirate. The earliest determinate lesion that can be recognized in breast tissue
      is ductal carcinoma in situ (DCIS). At the University of Texas M.D. Anderson
      Cancer Center, we have initiated a study to develop biomarkers for tamoxifen and
      4-hydroxyphenylretinamide by administering one or both of these drugs to women
      with DCIS or small invasive lesions in the interval between the initial
      diagnostic core biopsy and definitive surgery. The treatment is to be
      administered for 2-4 weeks. Proposed biomarkers to be studied include: (a)
      markers associated with neoplastic phenotypes, e.g., excessive proliferation,
      alternations of nuclear morphology and angiogenesis; (b) proteins likely to be
      required for response to the putative chemopreventive agents, e.g., estrogen
      receptor, nuclear retinoid receptors; (c) markers indicative of intact downstream
      response pathways, e.g., progesterone receptors; (d) oncogenes and tumor
      suppressor genes regulated by the proposed chemopreventive agents, e.g., neu, TGF
      beta; and (e) potential novel markers of genetic instability that could be
      studied in randomly obtained needle aspirates, i.e., random chromosomal gains and
      losses in high risk mammary epithelium. The experience gained in designing and
      conducting this trial is expected to facilitate development of future
      chemoprevention trials of breast, as well as other organ site cancers.

PMID- 8747375
TI  - Computer-assisted pathology of intraepithelial adenocarcinoma and related
      lesions: 3-D distribution, structural aberration and discrimination.
AB  - To discriminate among intraepithelial neoplasms, we have been relying on tissue
      microscopy, but pathologists' subjectivity sometimes impairs diagnosis. Even an
      individual pathologist is sometimes unable to reproduce exactly his or her own
      previous diagnosis. Are various atypical lesions classifiable in a reproducible
      way, and if they are, how? The reliability of a diagnosis will be strengthened if
      we can define the "natural" categories inherent in cells and tissues. Morphometry
      and statistical analysis using a computer can provide answers. Atypia, a
      morphological feature of carcinoma, is essentially multivariate. Quantification
      of a tissue feature requires reducing it to a set of ten or more quantities,
      including size, shape and position of the nucleus, nucleolus, and the cell
      itself. The grade of aberration from the norm can be assessed only by a synthetic
      approach, using a computer for multivariate cluster analysis. This classification
      has been attempted in adenocarcinoma and related lesions of the lung and
      pancreas. The categories thus established are reproducible, because the lesions
      fall into divisions according to their forms. We can also examine the organ
      distribution of intraepithelial neoplasms by three dimensional (3-D) computer
      assisted mapping. To reach a higher level of reliability, as many meaningful
      features as possible should be taken into account. Particularly, we emphasize the
      significance of architectural pattern as a biomarker for intraepithelial
      glandular neoplasms. Computer-aided 3-D structural analysis visualizes the basic
      skeleton of these neoplasms around which the cells adhere. Instead of the
      dichotomous tree pattern of normal glands, the tumors basically harbor a 3-D
      network, tubular or porous, which increasingly deviates from the norm along with
      the transition from adenoma to well to moderately to poorly differentiated
      adenocarcinoma. This structural aberration, if recognizable on 2-D sectional
      images, will serve as a surrogate endpoint biomarker for glandular tumors.

PMID- 8747376
TI  - Cervical cell recognition and morphometric grading by image analysis.
AB  - Cervical cell recognition by morphometric image analysis was compared to human
      visual cell recognition on the same 6,375 cells from 40 dysplastic, CIS,
      invasive, and 10 normal pap smears. The experimental approach defined receiver
      operating characteristic (ROC) curves for morphometric image analysis which could
      be rigorously compared to previously established human visual cell recognition
      ROCs on the same cells. Overall performance was measured Az, the area under the
      ROC curves in the two instances. For morphometric image analysis cell
      recognition, Az = 0.91, and for human visual cell recognition, Az = 0.87. These
      results clearly demonstrated that morphometric image analysis is equivalent to
      experienced human observers in ability to recognize isolated cells from cervical
      smears. An approach was also developed to link the ROC analytic methods of this
      study to a cytopathological or histopathological grading system, or "scale", that
      could be expressed in terms of normal deviate units of morphometric descriptors.
      This approach has the advantage of describing the grading scale in terms of its
      ROC characteristics; in essence, it describes performance for that grading scale
      at any decision point along the scale, if used for two-category classification.
      Additionally, This concept provides for a uniform final scale, regardless of
      which cells or tissues are graded. Also, this type of grading scale would
      automatically adjust itself for measurement variance for different types of cells
      or tissue, by reference to normal cells or tissues, so that a standard reference
      could be maintained.

PMID- 8747377
TI  - Image cytometry and chemoprevention in cervical cancer.
AB  - Of the approximately 60 million Pap smears performed in the United States in
      1995, about 8% or 5 million will show cytology that is "not negative" (ASCUS,
      AGCUS, LSIL, HSIL, etc.). Possibly 15% or about 0.7 million of these cases will
      have positive follow-up by repeated Pap smears, colposcopy or biopsy. More than 4
      million will be false-positive smears based on the reference standard of biopsy
      or repeated smears. If no treatment or medical intervention was offered to the
      0.7 million cytologically and histologically positive cases, perhaps 20,000 (3%)
      would develop into invasive cancer. Of the original 5 million cytologically "not
      negative" cases, fewer than 0.5% have the potential to develop into invasive
      cancer. While considerable attention has been paid to false-negatives in Pap
      screening, the above considerations indicate that the cytological and
      histological criteria for assessing the malignant potential of "not negative"
      samples might benefit from some refinement. Until such refinement occurs, any
      chemoprevention studies in cervix face a formidable signal-to-noise problem-
      worse than 1:30. This paper presents data from quantitative image cytometry of
      cervical smears for assessing the malignant potential of various "not negative"
      cases. We have approached this in two ways--by analyzing dysplastic cell nuclei
      and by analyzing the nuclei of cytologically normal cells growing in the vicinity
      of the neoplastic lesion. In both cases, nuclear features describing the
      distribution of the DNA in the cell nuclei (especially texture features) are the
      discriminating factors. Future research into the objective assessment of
      malignant potential of "not negative" cases is outlined.

PMID- 8747378
TI  - The molecular biology of cervical cancer.
AB  - Infections with specific high-risk of human papillomavirus constitute a major
      risk factor in the development of precancerous and cancerous lesions of the
      uterine cervix. Laboratory studies suggest that the human papillomavirus has a
      mechanistic role in development of these lesions. The two viral proteins
      consistently expressed in cervical carcinomas functionally abrogate critical cell
      cycle regulatory pathways, including those governed by the p53 tumor suppressor
      protein and the product of the retinoblastoma susceptibility gene, pRB.
      Subversion of these pathways by viral proteins causes genomic instability,
      resulting in the accumulation of chromosomal abnormalities followed by clonal
      expansion of malignant cells. Since continued expression of the papillomavirus
      proteins is critical for maintenance of the transformed state, they are
      attractive targets for prevention and therapy of precursor as well as cancerous
      lesions of the cervix.

PMID- 8747379
TI  - Perspective on cervical cancer: why prevent?
AB  - Cervical carcinoma (CC) remains a significant health problem in the United States
      (U.S.) despite the progressive fall in the mortality rate during the past 60
      years. However, CC is still the most common cancer among women worldwide and the
      leading cancer cause of death in many countries. In the U.S., the current age
      adjusted incidence of CC is about 8 per 100,000 population, which compares to
      54.6 in Peru and 4.2 in Israel. The lifetime risk for acquiring CC in the U.S. is
      about 1%, while the lifetime risk in Peru is more than 5 times greater. Recently
      some industrialized countries have reported a 2-3-fold increase in the death rate
      from CC among women less than 35 years of age. The primary strategy to reduce the
      incidence and death rate from CC is screening by cervical cytology. Because of
      the high incidence of CC precursor lesions, as well as the lack of specifically
      and sensitivity, CC screening has proven very costly. Nevertheless, in countries
      or regions where such screening has been repetitive and comprehensive, the
      mortality rate from CC has been reduced up to 80%, with most cases of CC
      occurring in non-compliant patients. The decrease in mortality results from
      detection of invasive cancer at an earlier, and therefore more curable stage, as
      well as detection and treatment of precursors which prevent the development of
      invasive carcinoma. Because the strategy involves detection of cancer precursors,
      the rate of abnormal Pap smears and the number of women requiring medical
      intervention is many times higher than the CC rate. The age-adjusted incidence of
      carcinoma in situ is reported to be 3-5-fold that of invasive cervical cancers.
      The age-adjusted incidence of all dysplasias is unknown, but it is reported that
      more than half (perhaps up to 90%) of mild and moderate dysplasias regress
      spontaneously. Considering that there are 15,000 cases of invasive cervical
      cancer diagnosed in the U.S. annually, cytologic screening involves the diagnosis
      and treatment of 750,000 or more women each year for precursor lesions. The
      impact of CC on the patient and society, as well as the role of other strategies
      for early diagnosis and prevention, will be briefly reviewed.

PMID- 8747380
TI  - Cervical intraepithelial neoplasia.
AB  - Cervical intraepithelial neoplasia (CIN) has been traditionally defined as a
      continuum of intraepithelial squamous abnormalities which exhibit nuclear atypia
      in all epithelial layers and possess some potential for progression to invasive
      carcinoma if not removed. Efforts to subdivide this spectrum into categories of
      low and high cancer risk have been based previously on the strong association
      between CIN III (carcinoma in situ) and subsequent invasive carcinoma. However,
      in practice, this distinction has been discouraged because CIN I and II may be
      associated with CIN III and a small proportion may progress to invasive
      carcinoma. As human papillomaviruses (HPV) have emerged as potential markers for
      subdividing precursor lesions, so-called "high-risk" HPV types have been
      associated with all grades of CIN, whereas "low-risk" HPV types have segregated
      primarily in lesions closely resembling condylomata. The place of condyloma in
      the spectrum of CIN, as well as the precise definition of CIN I, has been
      controversial. Some authors distinguish condyloma from CIN I and other use
      similar criteria for the diagnosis of both. Currently, the trend among
      pathologists and cytopathologists is to classify CIN I as a process either
      identical to or closely resembling condyloma (low-grade), and CIN II and III as
      lesions falling within the spectrum of CIN as classically described (high-grade).
      As new etiologic perspectives (HPV), classifications (Bethesda) and outpatient
      managements (LEEP) evolve, morphologic definitions of CIN will remain important
      to patient care, particularly if management decisions are based on nuances of
      histologic or cytologic grade. When using cervical lesion morphology as an
      endpoint in chemoprevention studies, investigators must understand that
      "morphologic progression" of CIN may not be synonymous with biologic progression,
      that discrepancies between HPV type and morphology exist, and that cytology and
      histology provide variable, and at times conflicting, information.

PMID- 8747381
TI  - Inhibition of proliferation and induction of apoptosis in cervical carcinoma
      cells by retinoids: implications for chemoprevention.
AB  - The effects of retinoids including all-trans-retinoic acid (ATRA), 13-CIS
      RETINOIC ACID (13CRA), and N-(4-hydroxyphenyl)retinamide (4-HPR) on several
      cervical carcinoma cell lines in culture were investigated as a prelude to
      investigating the mechanisms underlying the chemopreventive potential of
      retinoids in cervical cancer. We found that when used at a concentration of 1
      microM, 13CRA and ATRA inhibited the proliferation of three cell lines (ME-180
      [HPV 68], SiHa [HPV 18], and HT-3 [HPV-]) by about 80% after a seven-day
      treatment. Three other cell lines (MS-751 [HPV 18], HeLa [HPV 18], C-33A [HPV-])
      were moderately inhibited (30-48%), and two (C-4 II [HPV 18], CaSki [HPV 16])
      responded poorly (< 25% inhibition). 4-HPR failed to inhibit the growth of any of
      these cell lines when used at 1 microM; however, when used at 5 or 10 microM, it
      induced apoptosis as evidenced by DNA fragmentation in several of the cell lines
      and was more potent in this effect than 10 microM ATRA. Retinoids that induce
      apoptosis in malignant cells may be able to exert similar effects on premalignant
      cells. Such retinoids would be expected to exhibit greater potency as
      chemopreventive agents than retinoids that exert only cytostatic effects.

PMID- 8747382
TI  - Polyamines as biomarkers of cervical intraepithelial neoplasia.
AB  - Polyamines (putrescine, spermidine and spermine) play critical roles in cell
      growth and transformation. Ornithine decarboxylase (ODC), key enzyme in polyamine
      biosynthesis, is considered a putative protooncogene crucial to the regulation of
      cell growth and transformation. Cancer patients have elevated levels of
      polyamines in their physiological fluids compared to normal counterparts. alpha
      Difluoromethylornithine (DFMO), a specific suicide inhibitor of ODC, exhibits
      antitumor and antimetastasis activities, and displays effectiveness in many
      carcinogen-induced animal chemoprevention models. Therefore, we are using DFMO in
      a chemoprevention trial for cervical intraepithelial neoplasia grade III (CIN
      III), and evaluating patients for changes in polyamine metabolism as an
      intermediate marker of DFMO effect. A preliminary study showed that several
      milligrams of abnormal cervical biopsy tissue contained detectable levels of ODC
      activity and polyamines. Additionally, the presence of cadaverine suggested
      bacterial contamination of these tissues. For this reason, normal and abnormal
      biopsies collected during colposcopy were rinsed prior to frozen storage. In most
      patients, abnormal tissue showed greater ODC activities and lower
      spermidine/spermine ratios than normal tissues. Patients are now being treated
      with de-escalating doses of DFMO (1-0.06 g/m2/day) for one month. To study the
      effect of DFMO in patients with CIN III, we are collecting blood and cervical
      tissue specimens to measure the following parameters: plasma DFMO, ornithine and
      arginine levels; plasma N1-acetylspermidine levels; erythrocyte (blood polyamine
      carrier) free polyamine levels; cervical tissue free polyamine levels; cervical
      tissue N1-acetylspermidine levels; and cervical tissue ODC activities. N1
      acetylspermidine will be examined as this compound is known to exist primarily in
      tumor tissues, not in normal tissues. We therefore established a high-performance
      liquid chromatography method for N1-acetylspermidine. We expect to find that
      polyamines are effective markers in analyzing DFMO effects in this
      chemoprevention trial, thus functioning as pharmacodynamic parameters as well as
      biomarkers for transformation.

PMID- 8747383
TI  - Nutrient antioxidants in the pathogenesis and prevention of cervical dysplasias
      and cancer.
AB  - The role of nutritional factors in biochemical interactions that are part of an
      oncogenic process or inhibit free radical proliferation have attracted
      considerable interest in relation to molecular mechanism(s) and the natural
      history of human cancer. Epidemiologic and experimental studies have drawn
      attention to the association between dietary micronutrient deficiencies and the
      incidence of neoplastic and malignant lesions. In the last two decades, the
      role(s) of retinoids, carotenoids, tocopherols and water-soluble antioxidant
      vitamins, and allegations of anti-tumor properties in the daily dietary
      consumption of fresh fruits and green leafy vegetables, have captured the
      attention of an increasingly sensitive diet- and health care-conscious public,
      the biochemical community, and industrial food producers. Moreover, recent
      epidemiologic and compelling advances in molecular biology have linked the
      presence of restricted human papillomavirus (HPV) subtypes to cervical carcinoma
      and precursor lesions. In the present report, we identify and review measurable
      effects of dietary deficiencies of selected antioxidant micronutrients (i.e.,
      beta-carotene and vitamins A, C, and E) and their association with known cervix
      cancer risk factors in the pathogenesis and potential prevention of cervix
      dysplasias, presumed to be the precursor lesions of cervix cancer.

PMID- 8747384
TI  - Chemoprevention trials in the cervix: design, feasibility, and recruitment.
AB  - The cervix is an ideal organ for chemoprevention studies and the study of
      squamous carcinogenesis. In chemoprevention trial design, four factors are
      important: high-risk cohorts must be identified; suitable agents must be
      selected; study designs should include Phase 1, II, and III; and studies should
      include the use of surrogate endpoint biomarkers. High-risk cohorts can be
      selected for Phase I, II and III trials in the cervix, for example, patients with
      high grade lesions such as cervical intraepithelial neoplasia (CIN) grade 3 and
      carcinoma in situ (CIS). A Phase III trial might also include patients with
      lesions infected with oncogenic HPV types. The cervix is accessible and can be
      safely followed with Papanicolaou (Pap) smears and colposcopy. Suitable agents
      include those likely to work in squamous lesions, including retinoids,
      difluoromethylornithine, beta-carotene, and others. In Phase I chemopreventive
      studies, does are de-escalated rather than escalated, determining toxicity and
      optimal dose schedule. Phase II studies looking at effectiveness need placebo
      control groups since regression of high-risk lesions is possible. Phase III
      studies, now multicentric, should be carefully designed and include wide patient
      representation in order to evaluate the risk-benefit ratio of therapy, focusing
      on cancer incidence reduction. Surrogate endpoint biomarkers include quantitative
      histopathology, biologic measures of proliferation, regulation, differentiation,
      genetic instability, and fluorescence emission. Quantitative histopathologic
      markers include nuclear grading (i.e., shape, area, optical density, texture),
      nuclear pleomorphism, ploidy, and nucleolar size and position. Biomarkers under
      study at the present time in the cervix include proliferation markers (PCNA),
      regulation marker (EGFR, ras, myc, p53, retinoic acid receptors, ODC,
      spermidine/spermine ratios), differentiation markers (involucrin, cornifin,
      keratins), and markers of genetic instability (chromosome polysomy). Fluorescent
      spectroscopy uses light to probe the biochemical properties of tissue. This
      technique provides an automated diagnosis in real time with comparable
      sensitivity and specificity to colposcopy and can be used to monitor lesions in
      chemoprevention trials. Recruitment designs for cervix studies need to include a
      large referral population and patients with sufficiently large lesions.
      Clinicians involved in such studies need to stress contraception and smoking
      cessation, deal with language barriers, and provide compensation for child care
      and parking to patients in order to increase compliance.

PMID- 8747385
TI  - Surrogate endpoint biomarkers for cervical cancer chemopreventive trials.
AB  - Cervical intraepithelial neoplasia (CIN) represents a spectrum of epithelial
      changes that provide an excellent model for developing chemopreventive
      interventions for cervical cancer. Possible drug effect surrogate endpoint
      biomarkers are dependent on the agent under investigation. Published and
      preliminary clinical reports suggest retinoids and carotenoids are effective
      chemopreventive agents for CIN. Determination of plasma and tissue pharmacology
      of these agents and their metabolites could serve as drug effect intermediate
      endpoints. In addition, retinoic acid receptors could serve a both drug and
      biological effect intermediate endpoints. Possible biological effect surrogate
      endpoint biomarkers include cytomorphological parameters, proliferation markers,
      genomic markers, regulatory markers, and differentiation. Given the demonstrated
      causality of human papillomavirus (HPV) for cervical cancer, establishing the
      relationship to HPV will be an essential component of any biological intermediate
      endpoint biomarker. The pathologic effect surrogate endpoint biomarker for
      cervical cancer is CIN, used clinically for years. The desired effect for
      chemopreventive trials is complete regression or prevention progression. In
      planning chemoprevention trials, investigators need to consider spontaneous
      regression rates, the subjective nature of detecting CIN, and the impact of
      biopsy on regression. If intermediate endpoint biomarkers that met the above
      criteria were available for cervical cancer, then new chemopreventive agents
      could be rapidly explored. The efficacy of these new agents could be determined
      with a moderate number of subjects exposed to minimal risk over an acceptable
      amount of time. The impacts on health care for women would be significant.

PMID- 8747386
TI  - Statistical techniques for diagnosing CIN using fluorescence spectroscopy: SVD
      and CART.
AB  - A quantitative measure of intraepithelial neoplasia which can be made in vivo
      without tissue removal would be clinically significant in chemoprevention
      studies. Our group is working to develop such a technique based on fluorescence
      spectroscopy. Using empirically based algorithms, we have demonstrated that
      fluorescence is discriminating normal cervix from low- and high-grade cervical
      dysplasias with similar performance to colposcopy in expert hands. These
      measurements can be made in vivo, in near real time, and results can be obtained
      without biopsy. This paper describes a new method using automated analysis of
      fluorescence emission spectra to classify cervical tissue into multiple
      diagnostic categories. First, data is reduced using the singular value
      decomposition (SVD), yielding a set of orthogonal basis vectors. Each patient's
      emission spectrum is then fit by linear least squares regression to the basis
      vectors, producing a set of coefficients for each patient. Based on these
      coefficient values, the classification and regression tree (CART) method predicts
      the patient's classification. These results suggest that laser-induced
      fluorescence can be used to automatically recognize and differentially diagnose
      cervical intraepithelial neoplasia (CIN) at colposcopy. This method of analysis
      is general in nature, and can analyze fluorescence spectra of suspected
      intraepithelial neoplasms from other organ sites. As a more complete
      understanding of the biochemical and morphologic basis of tissue spectroscopy is
      developed, it may also be possible to use fluorescence spectroscopy of the cervix
      as a surrogate endpoint biomarker in Phase I and II chemoprevention trials.

PMID- 8747387
TI  - Clinical aspects of risk in women with endometrial carcinoma.
AB  - Carcinoma of the endometrium is the most common gynecologic malignancy, expected
      to account for 33,000 new cases and 6,000 deaths in 1995. Most endometrial
      cancers occur in postmenopausal women and produce abnormal vaginal bleeding. Some
      women exhibit the premalignant changes of atypical endometrial hyperplasia before
      developing an overt carcinoma. Identified epidemiologic risk factors include
      obesity, diabetes mellitus, use of unopposed exogenous estrogens, estrogen
      secreting tumors, and a reproductive history characterized by prolonged
      estrogenic predominance. Diagnosis can be readily established by outpatient
      endometrial biopsy. Because clinical estimates of disease extent and spread are
      subject to substantial error, endometrial cancer is now a surgically staged
      neoplasm. A well-defined set of surgicopathologic risk factors have been
      incorporated into the staging scheme. Women with extrauterine disease comprise
      about 20% of cases and are at greatest risk for tumor recurrence and death from
      disease. Within the much larger group of women whose tumors are limited to the
      uterus, recurrence risk can be stratified by cytologic grade, cell type, depth of
      myometrial invasion, and extension to the cervix. About two-thirds of women have
      low-risk disease confined to the uterus when these criteria are employed, while
      the remaining one-third have high-risk subtypes. Recent areas of investigation
      have focused on molecular and genetic markers. Two clinical observations
      currently being examined are the poorer survival of Black women with uterine
      cancer and the apparent association of endometrial lesions with chronic tamoxifen
      suppression in women with breast carcinomas.

PMID- 8747388
TI  - The role of computerized morphometric and cytometric feature analysis in
      endometrial hyperplasia and cancer prognosis.
AB  - In our hospital, quantitative cell and tissue analysis is routinely applied in
      endometrial (pre)malignancies. Reasons for this are higher accuracy,
      reproducibility and objectivity when compared to subjective assessment of type
      and grade, the possibility of detecting changes and differences, and better
      compatibility with clinical requests (two-class instead of three- or four-class
      system). Furthermore, prognostication is at least a good or better than with the
      usual subjective methods. Clinical prospective intervention trials are currently
      being set up.

PMID- 8747389
TI  - Quantitative cytopathology of endometrial lesions.
AB  - Morphometric and multivariate statistical methods were used to discriminate
      endometrial carcinoma from benign cells in cytologic studies. Clumps of
      epithelial cells that appeared most diagnostically relevant were selected from
      aspirated samples of 70 endometrial cancer patients. The cells' cytologic
      character was reduced to a combination of five quantitative parameters--nuclear
      size, degree of anisokaryosis, nuclear from index, homogeneity of nuclear
      chromatin texture, and regularity of nuclear arrangement. The 5-variate cluster
      analysis demonstrated that the 70 cases could be classified into three definite
      groups: Group A (17 cases) was characterized by cells of small nuclear size,
      slight anisokaryosis, homogeneous chromatin texture, and regular nuclear
      arrangement; Group C (12 cases) by cells of large nuclear size, marked
      anisokaryosis, heterogeneous chromatin texture, and irregular nuclear
      arrangement; and Group B (41 cases) by cells of intermediate parameter values.
      Group C was derived from 10 cases of adenocarcinoma and 2 of atypical
      hyperplasia, while Groups A and B were not derived from any cases of malignancy.
      The computer-assisted morphometric statistical method can objectively classify
      the endometrial cells into malignant and benign, with improved validity and
      reproducibility. The cytopathologic finding, if detected by this method, may
      serve as a surrogate endpoint biomarker.

PMID- 8747390
TI  - Epidemiology of endometrial neoplasia.
AB  - Though among U.S. women endometrial cancer is the most common invasive
      gynecological cancer, it has a relatively favorable prognosis. From 1986-1990,
      approximately 19% of U.S. Surveillance, Epidemiology and End Results (SEER)
      Program cases were diagnosed in women less than 55 years of age; however, the age
      specific incidence (per 100,000) peaked at 70-74 years (100.7), which was 2.85
      times the rate reported at 50-54 years (38.9). The incidence under 50 years was
      2.19 times higher in U.S. White compared with U.S. Black women; for uterine
      corpus cancers diagnosed at 50 years and older, the ratio declined but continued
      to be elevated in Whites (1.46). In contrast, average annual age-adjusted
      mortality (per 100,000) from 1986-1990 for uterine corpus cancer (1970 U.S.
      standard) was almost twice as high in U.S. Black women (6.0) as in U.S. White
      women (3.3). The determinants of age-specific elevated risks in mortality, in
      contrast to the lesser age-specific risks in incidence experienced by U.S. Black
      women compared with U.S. White women, may be explored with respect to
      socioeconomic and cultural factors that influence the distribution of
      epidemiologic risk factors such as reproductive history, choice of contraception
      methods, hormone replacement therapy, obesity, and dietary factors; age-specific
      prevalence of hysterectomy for other gynecological conditions; quality of medical
      care and surveillance practices; genetic factors influencing susceptibility; and
      tumor-associated biological factors. The majority of risk factors and medical
      conditions associated with endometrial cancer are related directly or indirectly
      to the levels and metabolic effects of the reproductive hormones, namely
      estrogens and progestogens. The molecular, genetic and epidemiologic
      characterization of endometrial cancer is attempting to delineate the multiple
      steps in the natural history of estrogen-induced or estrogen-responsive
      neoplasms.

PMID- 8747391
TI  - Endometrial cancer chemoprevention: implications of diverse pathways of
      carcinogenesis.
AB  - Endometrial cancers may be divided into two groups, reflecting differences in
      clinical behavior and pathogenesis. Endometrioid adenocarcinoma, which accounts
      for the majority of endometrial cancers, typifies the group of endometrial
      carcinomas that develop from atypical endometrial hyperplasia in the setting of
      excess estrogenic stimulation. In contrast, serous carcinomas are representative
      of endometrial tumors that occur in older women who have endometrial atrophy and
      lack the typical endometrial cancer risk factors reflecting unopposed estrogen
      exposure. Serous carcinomas are frequently associated with p53 abnormalities and
      appear to develop from a surface lesion termed endometrial intraepithelial
      carcinoma. Although serous carcinomas are rare, these highly aggressive tumors
      account for a disproportionate number of endometrial cancer deaths. Further
      delineation of the estrogen-dependent and estrogen-independent pathways of
      endometrial carcinogenesis may be useful in developing comprehensive
      chemopreventive approaches for endometrial cancer.

PMID- 8747392
TI  - Detection of occult endometrial carcinoma.
AB  - Endometrial carcinoma is commonly diagnosed as a consequence of abnormal uterine
      bleeding. In a study published in 1962, it was documented that endometrial cancer
      may be detected by vaginal pool smears in asymptomatic postmenopausal women. As a
      consequence of these observation, a systematic search for occult endometrial
      carcinoma was initiated in 1979, supported by a contract from the National Cancer
      Institute. The techniques used in this study and the problems encountered in the
      diagnosis of occult endometrial carcinoma will be discussed. Within 3-1/2 years
      of this study encompassing 2,586 peri- or postmenopausal women 16 occult
      endometrial carcinomas were discovered by direct endometrial sampling. Two
      carcinomas, missed on initial screening, were subsequently documented in this
      cohort, for a prevalence rate of 6.96 per 1,000. The incidence data based on
      follow-up examination of 1,754 women was 1.71 per 1,000 woman-years. An elaborate
      epidemiologic questionnaire was evaluated. Contrary to some prevailing views,
      obesity, hypertension, and diabetes failed to reach statistical significance as
      risk factors. The only risk factor of statistical value was delay in the onset of
      menopause past age 49, observed in about 50% of the cohort. It was noted that the
      administration of estrogens to women in Quetelet Index groups below means was
      more likely to be associated with carcinoma than in women in higher Quetelet
      groups but, again, the difference was not statistically significant. It was noted
      that in spite of an active search for endometrial hyperplasias, the rate of these
      lesions was nearly identical to the prevalence and incidence rates for carcinoma.
      It was postulated that some or perhaps most, endometrial carcinomas in
      postmenopausal women are not preceded by hyperplasia but originate ab initio in
      the endometrium.

PMID- 8747393
TI  - Biomarkers in the endometrium.
AB  - A number of oncogenes and tumor suppressor genes that may serves as surrogate
      biomarkers of transformation are altered during the process of endometrial
      carcinogenesis. Overexpression of HER-2/neu occurs in 10% of endometrial
      adenocarcinomas and correlates with intraperitoneal spread of disease and poor
      survival. The c-myc oncogene is amplified in 10% of cases. Point mutations in
      codon 12 of the K-ras oncogene have been reported to occur in 10-20% of
      endometrial cancers. K-ras mutations also have been noted in some endometrial
      hyperplasias, which may represent an early event in the development of some
      endometrial cancers. Mutation of the p53 tumor suppressor gene, with resultant
      overexpression of mutant p53 protein, occurs in 20% of endometrial
      adenocarcinomas. Overexpression of p53 is associated with advanced stage and poor
      survival. Because p53 mutations have not been observed in endometrial
      hyperplasias, this is thought to be a relatively late event in endometrial
      carcinogenesis. Microsatellite instability has also been noted in approximately
      15% of sporadic endometrial cancers, but mutations in DNA repair genes have not
      yet been reported. Chemoprevention trials in endometrial cancer may be feasible
      due to the existence of a premalignant lesion and surrogate biomarkers.

PMID- 8747394
TI  - Uterine neoplasms in patients treated with tamoxifen.
AB  - Since 1985, when Killackey originally described three cases of endometrial
      carcinoma in patients receiving tamoxifen, there have been several reports
      confirming or denying the relationship between tamoxifen and endometrial
      carcinoma. Our study of 15 patients treated for breast carcinoma with tamoxifen
      found that papillary serous carcinoma was the most common tumor in this group of
      patients. Several other retrospective studies reported a high incidence of high
      grade endometrioid adenocarcinoma or high-risk variants of endometrial carcinoma
      in patients receiving tamoxifen.

PMID- 8747395
TI  - Potential criteria for cohort selection in chemoprevention trials of uterine
      adenocarcinoma.
AB  - Women at risk of uterine cancer include those with one or more of the following
      characteristics: obesity, nulliparity, late menopause, diabetes mellitus,
      prolonged unopposed estrogen use, and tamoxifen therapy. Risk is additionally
      increased by the presence of endometrial hyperplasia. The incorporation of
      biomarkers into the selection criteria of cohort groups at risk for developing
      endometrial cancer offers an innovative approach to the clinical design of
      chemoprevention trials of endometrial adenocarcinoma. Biomarkers that may be
      useful in cohort selection include nuclear morphometry, specific genetic
      abnormalities, and markers of proliferation and differentiation.

PMID- 8747396
TI  - Prospective on ovarian cancer: why prevent?
AB  - In 1995, an estimated 26,600 women in the United States will be diagnosed with
      ovarian cancer. During that same year, approximately 14,500 women will die from
      the disease. Although ovarian cancer accounts for only 33% of the gynecologic
      cancers and only 5% of all cancers affecting women in the United States, it
      results in 55% of the deaths from gynecologic cancer and 6% of the cancer deaths
      in women. The cure rate for ovarian cancer by stage at diagnosis is not
      significantly different from other gynecologic cancers. Ovarian cancer confined
      to the ovary (Stage I) can be cured in 90% of cases. Survival for patients with
      advanced disease (Stage III and IV) is 21%. Unfortunately, while 73% of
      endometrial cancers, 55% of breast cancers, and 50% of cervical cancers are
      diagnosed as Stage I, only 23% of ovarian cancers are diagnosed as Stage I. Thus,
      five-year survival for all endometrial cancer is 85%, for all breast cancer, 82%,
      for cervical cancer, 70%, and for ovarian cancer, only 42%. The lack of early
      symptoms and the absence of any proven method of screening for early ovarian
      cancer results in over 70% of women being diagnosed after the disease has spread
      beyond the ovary. Also, unlike breast, cervical, and endometrial cancer, there is
      no known premalignant phase for ovarian cancer; therefore, diagnosis and
      treatment of a premalignant condition to prevent the development of ovarian
      cancer is not possible. Theories to explain the development of ovarian cancer are
      based on observation that ovulation inhibition through pregnancy, oral
      contraceptive use, and a shorter ovulatory period (late menarche or early
      menopause) result in a decreased incidence of ovarian cancer. The incessant
      disruption of the ovarian capsule followed by repair may provide the opportunity
      for aberrant growth. Finally, therapy of women with ovarian cancer usually
      requires multiple surgical procedures, multiple courses of chemotherapy, and
      results in significant morbidity and health care costs. For most with the
      disease, the end result will still be a slow, painful death by starvation. There
      should be little doubt based on the above statistics that every effort should be
      directed towards prevention of ovarian cancer. Possible strategies in the
      prevention of ovarian cancer should be directed toward determining if a
      premalignant condition exists, developing screening tools to detect premalignant
      disease or disease confined to the ovary, and developing interventions to prevent
      the development of the disease. It is well established that use of oral
      contraceptives for five or more years can result in up to a 50% reduction in the
      occurrence of epithelial ovarian cancer. Given the low complication rates from
      oral contraception use, this medication should be considered as a method of
      prevention, especially in high-risk groups. In addition, this is a realistic
      starting point for research into the development of preventive regimens.

PMID- 8747397
TI  - The epidemiology of ovarian cancer.
AB  - Ovarian cancer is the second most common cancer of the female reproductive system
      and the leading cause of death from gynecologic malignancies. In 1995, 26,600
      women will be diagnosed with ovarian cancer in the U.S., and 14,500 women will
      die from the disease. Between 1986-1900, the overall age-adjusted incidence was
      14.3/100,000 women; mortality was 7.8/100,000 women. Ovarian cancer, rare before
      age 40, increases steeply thereafter and peaks at ages 65-75. Incidence and
      mortality rates are higher among white women than among African-American women.
      Over the last three decades, ovarian cancer incidence has remained stable in high
      risk countries, while an increasing trend has been reported in low-risk
      countries. Despite recent advancements in treatment, the overall five-year
      survival rates continues to be low (39%). Over 70% of ovarian tumors are
      diagnosed when regional or distant involvement has already occurred, causing
      survival rates to remain stable. The etiology of ovarian cancer is poorly
      understood. Most studies have focused on the epidemiology of invasive epithelial
      ovarian tumors, while few have explored the epidemiology of epithelial tumors of
      low malignant potential and nonepithelial tumors. Factors associated with an
      increased risk for invasive epithelial ovarian cancer include age, race,
      nulliparity, family history of ovarian cancer, and history of endometrial or
      breast cancer. Factors associated with a reduced risk are history of one or more
      full-term pregnancies, use of oral contraceptives, history of breast feeding,
      tubal ligation, and hysterectomy. Other factors such as infertility drugs,
      hormone replacement therapy, age at menarche, age at menopause, dietary factors,
      lactose intolerance, talc use, coffee and alcohol consumption have been
      suggested, but their role is still inconclusive.

PMID- 8747398
TI  - Pathology of ovarian cancer precursors.
AB  - Ninety percent of ovarian cancers in the Western world are epithelial cancers
      derived from the surface epithelium of the ovary and its inclusion cysts. The so
      called surface epithelium is mesothelium that comes to resemble epithelium as it
      is reflected over the surfaces of the ovaries. At various ages, but particularly
      in women in the reproductive, menopausal, and postmenopausal age groups, this
      epithelium migrates into the ovarian stroma to form inclusion cysts. These cysts
      probably results from a dynamic interplay of surface epithelium and underlying
      ovarian stroma, but can also develop as a result of periovarian adhesions. There
      is abundant evidence that their formation is not related to repair of ovulation.
      It is generally accepted that benign and malignant ovarian epithelial tumors
      arise from surface epithelium and its cystic derivatives because they both, but
      particularly the latter, have a potential to differentiate into epithelia similar
      to those of normal mullerian derivation (tubal, endometrial, and endocervical
      epithelia) and their tumors resemble those of the fallopian tube, endometrium,
      and endocervix. Also, both intraepithelial carcinomas and precarcinomatous
      lesions can be observed in the surface epithelium and its cystic derivatives.
      These carcinomas may arise de novo or as a transformation of pre-existing benign
      tumors and non-neoplastic lesions of similar derivation. Surface epithelial
      inclusion cysts have a greater propensity to undergo neoplasia than does the
      surface epithelium itself. This difference has been recognized for many years
      most epithelial ovarian tumors are intraparenchymal, rather than being located on
      the ovarian surface. More recent evidence includes the immunohistochemical
      demonstration of various ovarian carcinoma antigens far more frequently in
      inclusion cyst epithelium than in surface epithelium; and the much more frequent
      presence of tubal metaplasia in the cyst epithelium than in the surface
      epithelium. Tubal metaplasia is encountered in non-neoplastic ovaries
      contralateral to ovarian carcinomas two to three times as frequently as in
      control ovaries, suggesting that the metaplastic epithelium is more prone to the
      development of carcinoma that non-metaplastic epithelium. Carcinoma precursors
      occur in the ovary, as in the cervix and endometrium, but have been reported only
      rarely because they are easily overlooked and have not been searched for by
      pathologists.

PMID- 8747399
TI  - Molecular approaches to prevention and detection of epithelial ovarian cancer.
AB  - More than 90% of epithelial ovarian cancers arise from single cells. Malignant
      transformation can be associated with a number of molecular alterations including
      upregulation of tyrosine kinases and phosphatases, physiologic activation o ras,
      mutation of p53, amplification of myc, and increased activity of matrix
      metalloproteinases 2 and 9. Proliferation of transformed epithelial cells can be
      enhanced through the persistence of autocrine growth stimulation by TGF-alpha,
      loss of autocrine growth inhibition by TGF-beta, as well as paracrine growth
      stimulation by macrophage derived cytokines and OCAF, a novel lyso-phospholipid.
      Ascites tumor cells retain responsiveness to growth inhibition by TGF-beta which
      induces apoptosis in malignant ovarian epithelial cells, but not in normal
      ovarian surface epithelium. Proliferation of surface epithelial cells following
      ovulation may contribute to the pathogenesis of ovarian cancer. Use of oral
      contraceptives that suppress ovulation has been associated with reduced risk of
      ovarian cancer in later life. Retinoids also deserve further evaluation for
      chemoprevention. Treatment with fenretinide was associated with decreased
      incidence of ovarian cancer. Additive or synergistic inhibition of ovarian tumor
      cell proliferation has been observed with TGF-beta in combination with all-trans
      retinoic acid. Early detection of ovarian cancer could improve survival.
      Transvaginal sonography (TVS) and serum markers such as CA-125 have been
      evaluated in multiple clinical trials. The former lacks adequate specificity,
      whereas the latter is not sufficiently sensitive. Use of multiple serum markers
      can improve sensitivity. A combination of CA-125, M-CSF and OVX-1 has detected >
      95% of Stage I ovarian cancers. If similar results are obtained with different
      data sets, multiple serum markers could be used to trigger the performance of
      TVS, providing a potentially cost effective screening strategy. Prospective
      trials will be required to demonstrate that screening for early stage ovarian
      actually impacts on survival.

PMID- 8747400
TI  - Biomarkers in the ovary.
AB  - Alterations in specific oncogenes and tumor suppressor genes that serve as
      surrogate markers of malignant transformation have been identified in ovarian
      cancers. Overexpression of the HER-2/neu oncogene occurs in approximately 30% of
      breast and ovarian cancers. In most studies, HER-2/neu overexpression has
      correlated with poor survival. Although mutation of the K-ras oncogene has been
      found in some mucinous ovarian cancers, mutations in this gene appear to be more
      common in borderline ovarian tumors. Amplification of c-myc occurs in
      approximately 30% of ovarian cancers and is more frequently seen in serous
      cancers. Mutation of the p53 tumor suppressor gene, with resultant overexpression
      of mutant p53 protein, occurs in 50% of Stage III/IV and 15% of Stage I/II
      ovarian cancers. Most p53 mutations in ovarian cancers are transitions, which
      suggests that they arise spontaneously rather than due to exogenous carcinogens.
      In contrast to the acquired genetic alterations described above that are a
      feature of sporadic ovarian cancers, a small fraction of epithelial ovarian
      cancers arise due to inherited genetic defects. Recently, the BRCA1 tumor
      suppressor gene on chromosome 17q was identified and shown to be responsible for
      some cases of hereditary breast and ovarian cancer. Families in which mutations
      in this gene exist are usually characterized by early age of disease onset.
      Presently, it remains unclear what fraction of hereditary ovarian cancers are due
      to BRCA1 mutations.

PMID- 8747401
TI  - Screening for ovarian cancer: what are the optimal surrogate endpoints for
      clinical trials?
AB  - The inability to identify relevant markers for presymptomatic screening in early
      stage or "preinvasive" ovarian cancer has plagued investigators and clinicians
      facing the problems of early detection. The characteristic late stage of disease
      at initial presentation has hindered our understanding of the biologic
      progression and stepwise molecular alterations that result in ovarian carcinoma.
      To date, most screening studies have focused on identifying early anatomic
      changes using ultrasound or fluctuations in serum biomarkers such as CA-125.
      These screening methodologies have proven inadequate in both sensitivity and
      specificity for early stage ovarian cancer detection. Molecular analysis of
      ovarian carcinomas has revealed alterations in oncogenes and tumor suppressor
      genes associated with these tumors. The HER-2/neu oncogene, a member of the
      epidermal growth factor family, is amplified or overexpressed in approximately 25
      30% of ovarian carcinomas. Significant data substantiate an important role for
      HER-2/neu in the pathophysiology of ovarian cancer. While potentially an
      attractive surrogate endpoint biomarker (SEB), serum HER-2/neu levels have not
      proven to be a useful screening modality. In response to the urgent need for
      improved early detection for ovarian cancer, our current research efforts include
      differential hybridization studies between normal and malignant ovarian
      epithelium to define potentially unique ovarian cancer antigens which may
      ultimately have utility; defining physical alterations that occur in malignant
      ovarian tissues using implanted telemetry systems; studies using positron
      emission tomography to detect changes in glucose metabolism between normal and
      malignant ovarian tissues; and screening studies using a 3-dimensional ultrasound
      unit to improve the accuracy of this technique in recognizing early neoplastic
      changes. By taking diverse approaches to tackle this problem, an improved
      understanding of ovarian carcinogenesis should translate into the identification
      of appropriate SEBs for early detection.

PMID- 8747402
TI  - Early detection and screening for ovarian cancer.
AB  - Ovarian cancer is associated with postmenopausal women of North American or
      European descent, nulliparous women, and women with a first-degree relative with
      an epithelial ovarian cancer. Methods for early detection of ovarian cancer are
      the pelvic examination, ultrasound techniques, and CA-125 monitoring, none of
      which are highly sensitive or specific for the disease. At the Yale-New Haven
      Medical Center, first-degree relatives of women with epithelial ovarian cancer
      were invited to participate in an intense ovarian cancer screening program
      consisting of tumor markers, endovaginal ultrasound and color Doppler flow
      studies, and physical examinations performed in a serial fashion. The false
      positive rate for the tumor markers varied from 2 to 9% at initial evaluation of
      the first 247 participants. Endovaginal ultrasound and color Doppler flow
      techniques were used to evaluate 326 ovaries in 169 women. Resistive indices <
      0.5 were present in 26 ovaries (8.4%), and peak systolic velocities > 30 cm/sec
      occurred in 7 ovaries (2.3%). To date, four breast cancers have been detected,
      three cervical intraepithelial neoplasias have been identified, and three
      atypical adenomatous hyperplasias were diagnosed. No epithelial ovarian cancer
      was found. Isolated screening for ovarian cancer even in high-risk women is not
      cost effective. Women screened for ovarian cancer should also be evaluated for
      cancers of the breast, cervix, colon, rectum and endometrium. Isolated abnormal
      screening test values are not an indication for surgery.

PMID- 8747403
TI  - Office laparoscopy as a screening tool for early detection of ovarian cancer.
AB  - Laparoscopy is a safe and effective surgical procedures used in evaluating the
      peritoneal cavity. Laparoscopy, under local anesthesia, has been well documented
      in the literature. These studies support the concept that laparoscopy can be
      performed under local anesthesia. Several small studies have addressed the
      respiratory, cardiac, and hemodynamic changes observed using local anesthesia and
      suggest that, with proper monitoring, these procedures can be safely performed in
      an outpatient setting. Optical catheter systems now have diameters ranging from
      0.25 mm to 2.5 cm. Image fibers 6 microns in diameter are combined in bundles.
      The catheter system produces a brighter though grainier picture than views
      produced by a xenon light source and a 5 mm laparoscope. An Adair Verres needle
      (18 gauge) is inserted through a 3 mm plastic introducer. The Adair Verres needle
      is removed and a gas extension tube is used to create a pneumoperitoneum with
      carbon dioxide. The optical catheter is placed through the extension tube. If a
      second site is required for biopsy or washings, a 3 mm port can be inserted under
      direct visualization. Miniature ultrasound transducers have now been developed as
      a means of imaging the internal structures of the ovary. These transducers,
      housed in #3.5-6.2 French catheters, can be passed through a laparoscope, adding
      a new dimension to laparoscopy. Although the technology of office laparoscopy as
      a means of detecting early ovarian cancer exists, it has limited applicability
      for screening the population at large. It may be more useful as secondary or
      tertiary testing in the work-up of patients suspected of having ovarian cancer.

PMID- 8747404
TI  - Potential criteria for cohort selection in chemoprevention trials of epithelial
      ovarian cancer.
AB  - Epithelial ovarian cancer is a heterogeneous disease. Epidemiologic studies have
      identified risk factors for this disease including advanced age, nulliparity,
      history of infertility, early age at menarche, late age at menopause, and perhaps
      ovulation induction. Cohort selection that includes women who have potential
      precursor lesions and alterations of select biomarkers may prove useful in the
      design of chemoprevention trials of epithelial ovarian cancer. Nuclear
      morphometry, specific genetic alterations, and markers of proliferation and
      differentiation may be useful biomarkers to monitor the efficacy of specific
      interventions.

PMID- 8747405
TI  - Pharmacogenetics in the new patterns of healthcare delivery.

PMID- 8747406
TI  - Genetic polymorphism of cytochrome P4502E1 and risk of alcoholic liver disease in
      Caucasians.
AB  - Genetic factors may be of importance in determining inter-individual
      susceptibility to alcoholic liver disease (ALD). Among the candidate genes which
      have been considered to be important are those which code for enzymes involved in
      alcohol metabolism. Cytochrome P4502E1 (CYP2E1) metabolizes alcohol to
      acetaldehyde and the hydroxyethyl radical, and is also inducible by alcohol. A
      Rsa I restriction fragment length polymorphism (RFLP) in the 5'-flanking region
      of the CYP2E1 gene has been identified by other investigators, studies showing
      that the mutant allele (termed c2) shows greater transcriptional activity, higher
      protein levels and increased activity compared with the wild-type allele (c1). We
      have used PCR-RFLP analysis to determine whether the frequency of these alleles
      differed in 95 Caucasian patients with ALD compared with 205 control subjects
      (comprising 58 alcoholics with no liver disease, 47 patients with non-alcoholic
      liver disease and 100 healthy volunteers). In controls, the frequency (0.024) of
      the c2 allele was similar to that previously reported in other Caucasian
      populations. The c2 allele frequency in patients with ALD (0.1), however, was
      significantly (p = 0.0003; odds ratio (OR) 4.5, 95% CI 1.9-10.9) higher than in
      control subjects. The findings indicate that Caucasians carrying the Rsa I c2
      allele of the CYP2E1 gene may be at higher risk of developing ALD if they abuse
      alcohol.

PMID- 8747407
TI  - Use of omeprazole as a probe drug for CYP2C19 phenotype in Swedish Caucasians:
      comparison with S-mephenytoin hydroxylation phenotype and CYP2C19 genotype.
AB  - A single oral dose of omeprazole (20 mg) was given orally to 160 healthy
      Caucasian Swedish subjects and tested as a probe for CYP2C19. The study was
      nonrandomized and included seven subjects previously classified as poor
      metabolizers (PM) of S-mephenytoin. The ratio between the plasma concentrations
      of omeprazole and hydroxyomeprazole (metabolic ratio; MR) was determined by HPLC
      in a blood sample drawn 3 h after drug intake. In 17 subjects the test was
      repeated and the MRs of omeprazole on the two occasions were correlated (rs =
      0.85; p < 0.0001). There was a significant correlation between the MR of
      omeprazole and the S/R mephenytoin ratio among 141 subjects, in whom both ratios
      were determined (rs = 0.63, p < 0.001). All seven PMs of S-mephenytoin had higher
      MRs of omeprazole (7.1-23.8) than extensive metabolizers (EM) (0.1-4.9). All 160
      subjects and another 15 Caucasian Swedish PMs previously phenotyped with
      mephenytoin were analysed with respect to the presence of the CYP2C19m1 allele by
      PCR amplification of the intron 4/exon 5 junction followed by Sma I digestion.
      EMs heterozygous for the CYP2C19m1 gene had MRs of omeprazole and S/R ratios of
      mephenytoin that were higher than those of subjects who were homozygous for the
      wild-type allele (p = 0.0001). Nineteen of the 22 PMs were homozygous for the
      CYP2C19m1 gene. Three were heterozygous for this allele. Thus, 41 of the 44
      alleles (93%) of PMs were defective CYP2C19m1. One of the remaining three PM
      alleles was subsequently found to contain the CYP2C19m2 mutation, which has
      earlier been shown to be associated with the PM phenotype in Oriental
      populations. In conclusion, the phenotype determined by omeprazole correlated
      with that of mephenytoin, and was in good agreement with the genotype.

PMID- 8747408
TI  - Fetal mouse susceptibility to transplacental carcinogenesis: differential
      influence of Ah receptor phenotype on effects of 3-methylcholanthrene, 12
      dimethylbenz[a]anthracene, and benzo[a]pyrene.
AB  - Genetic backcrosses of C57BL/6 and DBA/2 mice were used to examine the influence
      of maternal and fetal polymorphisms at the Ahr locus on susceptibility to
      transplacental carcinogenesis by 3-methylcholanthrene, 7,12
      dimethylbenz[a]anthracene, and benzo[a]pyrene. (C57BL/6 x DBA/2) F1 mothers were
      backcrossed to DBA/2 males, and DBA/2 females to F1 males to produce both Ahr
      responsive (Ah+) and nonresponsive (Ah-) fetuses carried by mothers that were
      themselves either Ah+ or Ah-. 3-Methylcholanthrene was given intragastrically on
      gestation days 13-18 and 7,12-dimethylbenz[a]anthracene or benzo[a]pyrene on day
      17 as a single intraperitoneal dose. Ahr phenotype was determined by the
      zoxazolamine sleeping time test after beta-naphthoflavone pretreatment at 6 weeks
      of age. The offspring were examined for tumours at 1 year. Both 3
      methylcholanthrene and 7,12-dimethylbenz[a]anthracene treatments resulted in a
      two- to five-fold greater incidence and multiplicity of lung and liver tumours in
      the Ah+ offspring compared with that in Ah- littermates. By contrast, there was
      no difference between Ah+ and Ah- offspring with regard to numbers of tumours
      caused by benzo[a]pyrene. Maternal Ahr phenotype appeared to play a role also, in
      that the offspring of the Ahr-responsive F1 mothers developed fewer tumours per
      unit dose than those of the nonresponsive DBA/2 mothers. The effect of maternal
      phenotype on risk was three- to five-fold. Fetal and maternal phenotype combined
      yielded a 10- to 20-fold risk differential for transplacental carcinogenesis by
      the methylated compounds, with greatest risk experienced by responsive fetuses in
      nonresponsive mothers, and least by nonresponsive progeny of responsive mothers.

PMID- 8747409
TI  - An efficient strategy for detection of known and new mutations of the CYP2D6 gene
      using single strand conformation polymorphism analysis.
AB  - To detect mutations in the cytochrome P450 CYP2D6 gene (CYP2D6), we developed a
      strategy based on single-strand conformation polymorphism (SSCP) analysis of the
      gene amplified by polymerase chain reaction (PCR). The efficiency of the method
      was evaluated by analysing DNA samples from extensive metabolizers (EM) and poor
      metabolizers (PM) of debrisoquine. Haplotypes, alleles and mutations of CYP2D6
      had previously been characterized in each individual using PCR assays, Xba I
      restriction fragment length polymorphism (RFLP) and sequencing. PCR-SSCP results
      were in complete agreement with those obtained using established methods. All
      previously characterized mutations were associated with particular shifts in the
      electrophoretic mobility of DNA fragments allowing their identification. We
      further tested the efficiency of PCR-SSCP for detecting new CYP2D6 mutations. DNA
      from a PM subject presumed to carry an unknown non-functional mutant allele of
      CYP2D6 was amplified and bands with aberrant migration patterns were observed on
      SSCP gels. Sequence analysis of the corresponding DNA fragments revealed the
      causative mutations. In this way, a novel non-functional allele of the gene,
      carrying three previously reported mutations and a new mutation in the third exon
      which results in a premature termination codon, was characterized. Finally,
      CYP2D6 SSCP analysis was performed on DNA amplified with fluorescent primers and
      an automated DNA sequencer was used for SSCP analysis of products. We conclude
      that the PCR-SSCP approach is a powerful method of identifying simultaneously
      known and new mutations of the CYP2D6 gene.

PMID- 8747410
TI  - R296C and other CYP2D6 mutations in Chinese.

PMID- 8747411
TI  - Genetic polymorphism of CYP2C9 and its effect on warfarin maintenance dose
      requirement in patients undergoing anticoagulation therapy.

PMID- 8747412
TI  - Anatomy of the jaw, dentition, and related regions.
AB  - The jaw has traditionally been evaluated by dentists and oral surgeons using
      conventional panoramic and intraoral films. Recently, CT software programs
      specifically developed to evaluate dental implant patients have provided
      radiologists with a new window through which to assess anatomy and pathology of
      the jaw. The anatomy of this region, including the dentitian, and related
      structures are discussed in this section.

PMID- 8747413
TI  - Dental implants and dental CT software programs.
AB  - Dental implants are titanium cylinders that are surgically implanted into the jaw
      to allow fixation of a permanent dental prosthesis. These have provided an
      attractive alternative to standard removable dentures and have become quite
      popular. To assess these patients preoperatively, CT software programs were
      developed that display multiple axial, cross-sectional, and panoramic images of
      the jaw. As a result, new dialogues and interactions were created between
      radiologists and dentists, and this in turn brought new territories and
      unfamiliar diseases to the radiologists' view. The purpose of this article is to
      familiarize the radiologist with dental implants, the surgical procedure, dental
      CT software programs, and related dental pathology.

PMID- 8747414
TI  - Lesions of the jaws.
AB  - Jaw lesions are relatively common findings on imaging studies of the lower face.
      The intent of this article is to present an approach to the diagnosis of lesions
      involving the maxilla and mandible based on their radiographic appearance and
      location. The radiographic and computed tomographic appearances of a number of
      lesions occurring in the maxilla and mandible are presented.

PMID- 8747415
TI  - Imaging of the temporomandibular joint.
AB  - Recent advances in imaging technology have greatly contributed to the
      understanding of diseases of the temporomandibular joint (TMJ). MRI is now the
      modality of choice in the evaluation of TMJ-related symptoms. This article
      describes normal anatomy and MRI characteristics of diseases affecting the TMJ
      including internal derangement, inflammation, and tumors.

PMID- 8747416
TI  - Oral cavity: anatomy and pathology.
AB  - The oral cavity and oropharynx comprise the upper portion of the aerodigestive
      tract. These two regions are distinguished from each other because pathologic
      processes differ in their presentations, prognoses, and histologic grades. The
      normal anatomy of the oral cavity, vestibule, and oral cavity proper is discussed
      and is followed by a discussion of the sublingual and submandibular spaces. The
      diversity of pathologic processes that occur in these regions is then presented
      as well as the more common pitfalls.

PMID- 8747417
TI  - Imaging of the salivary glands.
AB  - CT and MRI have greatly facilitated evaluation of pathology of the three pairs of
      major salivary glands and the hundreds of minor salivary glands. Imaging can
      frequently offer a specific histological diagnosis for benign and malignant
      neoplasms of the parotid, submandibular, and sublingual glands. Obstruction,
      infection, autoimmune processes, and congenital anomalies also are readily
      diagnosed. CT and MRI studies assess the anatomic extent of minor salivary gland
      neoplasms. Sialography continues to provide useful information about intrinsic
      abnormalities of the parotid and submandibular ducts.

PMID- 8747418
TI  - Advanced application of magnetic resonance imaging in human brain science.
AB  - Magnetic resonance imaging (MRI) has revolutionized the practical demands of
      clinical neurology. This technology promises now to advance neurology in
      theoretical and applied realms of fundamental human brain science. We emphasize
      here two domains in which these advances will occur. The first is volumetric
      morphometry of the human brain. With MRI the multiple levels of processing of the
      brain may be characterized in terms of their absolute volumes and their relative
      sizes, perspectives indispensable for our understanding of the development and
      operation of neural systems. Volumetric morphometry also promises substantial
      increases in the specificity and sensitivity of neurological diagnosis,
      particularly where applied to disorders where structural abnormalities will be
      reflected only in volumetric abnormalities. The second direction of advance
      considered here is application of MRI in cortical mapping in support of cognitive
      neuroscience. In this application MRI provides means to map at high resolution
      the distribution of subcomponents of neural systems activated by behavioral
      paradigms. This line of investigation will carry forward rapidly our
      understanding of how the information processing algorithms of the brain are
      mapped upon the coordinates of the various gray matter structures of the brain.
      Among the practical consequences of this application will be a reasoned design of
      surgical field in tumor and epilepsy surgery.

PMID- 8747419
TI  - Correlation of 99mTc-HMPAO SPECT with EEG monitoring: prognostic value for
      outcome of epilepsy surgery in children.
AB  - Sixteen children who had focal cortical resections for medically intractable
      epilepsy were preoperatively evaluated with 99mtechnetium-labelled
      hexamethylpropyleneamineoxime single photon emission computed tomography (99mTc
      HMPAO SPECT). Video-EEG monitoring was performed in all patients. Outcome was
      assessed according to the criteria of Engel et al. [1], at a mean follow up
      length of 13.4 +/- 8.7 months, in all patients. Interictal SPECT showed
      appropriate localization in 11/15 cases, of whom nine had a class 1 outcome and
      two had class 2 and 4 outcomes. Interictal SPECT did not correlate with ictal EEG
      in 4/15 patients, of whom two had a class 1 outcome, and two had class 3 and 4
      outcomes. Two postictal studies obtained in group I showed good correlation with
      the area of ictal EEG onset, and both patients had a class 1 outcome. Interictal
      HMPAO SPECT imaging, when positively correlated with the ictal EEG focus or with
      the site of surgery determined by other means, may have prognostic value for
      outcome of cortical resections for epilepsy in children. The use of ictal and
      post-ictal studies shows promise for further improving prognostic information in
      this population.

PMID- 8747420
TI  - Posterior fossa cystic lesions--magnetic resonance imaging manifestations.
AB  - Cystic lesions of the posterior fossa remain a controversial subject as to
      clinical classification and diagnosis, especially for those in combination with
      other intracranial abnormalities. During the period of November 1985 to June
      1991, 16 patients with cystic lesions of the posterior fossa were retrospectively
      reviewed on neuroradiological evaluation with MR images. The patients were 9
      males and 7 females aged from 5 days to 15 years old (medium 1 year old). They
      were classified into three groups as Dandy-Walker cyst (group A, 5 patients),
      mega cisterna magna (group B, 4) and retrocerebellar pouch or cyst (group C, 7).
      Nine patients had associated intracranial anomalies, holoprosencephaly in 3
      (group A, 3), dysgenesis of the corpus callosum in 4 (group A, 2; group C, 2),
      and occipital meningoceles in 2 (group C, 2). Hydrocephalus or ventricular
      enlargement was found in 10 patients (group A, 5; group B, 2; group C, 3).
      Surgical treatment (cyst-peritoneal shunt or cystectomy) was performed for 10
      patients with clinical symptoms due to cyst. Postoperatively, clinical symptoms
      due to increased intracranial pressure or hydrocephalus improved in 7 patients.
      For long-term results, the cyst was reduced in 1 of 5 patients of group A and 2
      of 5 of group C. Most of our patients have a poor prognosis because of the
      associated intracranial anomalies or atrophy of the cerebellum. Multiplanar MR
      images may provide sufficient evidence for the diagnosis of posterior fossa
      cysts, especially in the case of rotation or upward displacement of the
      cerebellar vermis. However, the cyst membrane, and the communication of fluid
      between the cyst and the cistern, cannot be demonstrated on MR images. Further
      investigation on these subjects and indications for surgical intervention is
      highly necessary.

PMID- 8747421
TI  - Clinico-neuropathological study of incontinentia pigmenti achromians--an autopsy
      case.
AB  - A clinico-neuropathological study of a Japanese girl with hypomelanosis of Ito,
      one of the neurocutaneous syndromes, is reported. At birth, typical skin
      hypopigmentation on the trunk and a hypopigmented streak on the left lower
      extremity were noted. From 2 months of age, intractable convulsions occurred and
      EEG showed various abnormalities. Psychomotor development was severely retarded
      and she died of pneumonia at the age of 13 months. Neuropathological examination
      revealed brachycephaly, micropolygyria and asymmetry of lateral ventricles. A
      histological examination showed a disarray of cortical lamination, and the
      existence of nerve cells in the white matter. These pathological findings showed
      a migration anomaly during brain maturation.

PMID- 8747422
TI  - Circadian rhythm abnormalities in adrenoleukodystrophy and methyl B12 treatment.
AB  - A 13-year-old male with adrenoleukodystrophy (ALD) developed a sleep-wake
      disorder after complete vision loss. He had a 25-h sleep-wake cycle. After methyl
      B12 therapy, circadian rhythms in his plasma melatonin and beta-endorphin levels
      approximated those of healthy volunteers, and his peak cortisol time shifted
      backward. Daily deep body temperature (DBT) amplitude was smaller than in healthy
      males before and after the treatment, and his acrophase did not change. However,
      his sleep-wake rhythm became normal. Methyl B12 is considered useful for treating
      circadian rhythm disturbances in patients having central nervous system disorders
      and blindness.

PMID- 8747423
TI  - Preservation of central motor conduction in patients with spinal muscular atrophy
      type II.
AB  - We evaluated the central (motor cortex to C8 motoneuron) and peripheral (C8
      motoneuron to the muscle) motor conduction in 14 limbs of 7 patients with the
      intermediate form of spinal muscular atrophy (SMA II). The central motor
      conduction time (CMCT) was calculated using motor evoked potentials (MEPs) by
      transcranial magnetic stimulation and the results of a conventional F wave study.
      Peripheral conduction abnormality was found in 6 median nerves (43%) and 10 ulnar
      nerves (71%). Even in these patients with peripheral conduction abnormalities,
      the CMCT was consistently normal whenever the MEP was recorded. These results
      indicate that the motor conduction of the corticospinal fibers remains normal in
      SMA II.

PMID- 8747424
TI  - Interaction of synthetic Alzheimer beta-protein-derived analogs with aqueous
      aluminum: a low-field 27Al NMR investigation.
AB  - Synthetic peptides corresponding to the soluble Alzheimer beta-protein, i.e.,
      beta 1-40 and beta 6-25, were utilized to investigate the association of aluminum
      using low-field 27Al nuclear magnetic resonance (NMR) spectroscopy and reversed
      phase high-performance liquid chromatography (RP-HPLC). Addition of beta 1-40 or
      beta 6-25 to aqueous Al3+ gives rise to a 27Al NMR signal corresponding to the
      association of Al3+ with the peptides; this effect is not easily reversed by
      EDTA. Based on the relative intensity of the Al(3+)-peptide signal between pH 4
      and 6, there are at least 4 Al3+ ions associated with each peptide molecule.
      Microheterogeneity is observed with RP-HPLC on incubating solutions of Al3+ with
      beta 1-40 and beta 6-25. The 27Al NMR spectra of chromatographically pure
      fractions of beta 1-40 and beta 6-25 indicate that the peptide-associated Al3+ is
      released below pH 3.5. We propose that soluble beta 1-40 provides an anchor for
      Al3+ to bind, eventually leading to an increased deposition of amyloid in the
      Alzheimer brain.

PMID- 8747426
TI  - A comparison of calcium binding in Callinectes sapidus premolt and postmolt
      cuticle homogenates: implications for regulation of biomineralization.
AB  - Cuticle tissue homogenates (CTHs) from Callinectes sapidus premolt cuticle bound
      approximately 367% more Ca2+ ions than did those from the postmolt cuticle. The
      pH-stat assay which was used to compare in vitro CaCO3 nucleation times confirmed
      that the premolt CTHs had greater inhibitory activity than did the postmolt CTHs.
      This inhibitory activity was indicated by CaCO3 nucleation times in excess of
      control values. Premolt nucleation times exceeded those of postmolt samples by
      approximately 340%. A positive correlation was observed between Ca2+ binding and
      calcification inhibitory activity for both premolt and postmolt CTHs. Heat
      pretreatment of CTHs at 70 degrees C for a 24-hr period had no significant effect
      on their Ca2+ binding. However, this heat pretreatment decreased their
      calcification inhibitory activity. Pretreatment of CTHs with Ca2+ diminished
      their calcification inhibitory activity. These results are consistent with a
      mechanism for inhibition of biocalcification by these proteins which involves
      their initial reversible binding to nascent calcite nuclei growth steps and
      kinks, rather than their in vivo interaction with free Ca2+ ions in solution.

PMID- 8747425
TI  - Conserved cystatin segments as models for designing specific substrates and
      inhibitors of cysteine proteinases.
AB  - Peptide segments derived from consensus sequences of the inhibitory site of
      cystatins, the natural inhibitors of cysteine proteinases, were used to develop
      new substrates and inhibitors of papain and rat liver cathepsins B, H, and L.
      Papain hydrolyzed Abz-QVVAGA-EDDnp and Abz-LVGGA-EDDnp at about the same rate,
      with specificity constants in the 10(7) M-1 sec-1 range; cathepsin L also
      hydrolyzes both substrates with specificity constants in the 10(5) M-1 sec-1
      range due to lower k(cat) values, with the Km's being identical to those with
      papain. Only Abz-LVGGA-EDDnp was rapidly hydrolyzed by cathepsin B, and to a
      lesser extent by cathepsin H. Peptide substrates that alternate these two
      building blocks (LVGGQVVAGAPWK and QVVAGALVGGAPWK) discriminate the activities of
      cathepsins B and L and papain. Cathepsin L was highly selective for cleavage at
      the G-G bond of the LVGG fragment in both peptides. Papain and cathepsin B
      cleaved either the LVGG fragment or the QVVAG fragment, depending on their
      position within the peptide. While papain was more specific for the segment
      located C-terminally, cathepsin B was specific for that in N-terminal position.
      Peptidyl diazomethylketone inhibitors based on these two sequences also reacted
      differently with papain and cathepsins. GlcA-QVVA-CHN2 was a potent inhibitor of
      papain and reacted with papain 60 times more rapidly (k + 0 = 1,100,000 M-1 sec
      1) than with cathepsin L, and 220 times more rapidly than with cathepsin B.
      Cathepsins B and L were preferentially inhibited by Z-RLVG-CHN2. Thus cystatin
      derived peptides provide a valuable frame-work for designing sensitive, selective
      substrates and inhibitors of cysteine proteinases.

PMID- 8747427
TI  - Extensive modifications for methionine enhancement in the beta-barrels do not
      alter the structural stability of the bean seed storage protein phaseolin.
AB  - Common beans are widely utilized as a food source, yet are low in the essential
      amino acid methionine. As an initial step to overcome this defect the methionine
      content of the primary bean seed storage protein phaseolin was increased by
      replacing 20 evolutionarily variant hydrophobic residues with methionine and
      inserting short, methionine-rich sequences into turn and loop regions of the
      protein structure. Methionine enhancement ranged from 5 to 30 residues. An
      Escherichia coli expression system was developed to characterize the structural
      stability of the mutant proteins. Proteins of expected sizes were obtained for
      all constructs except for negative controls, which were rapidly degraded in E.
      coli. Thermal denaturation of the purified proteins demonstrated that both wild
      type and mutant phaseolin proteins denatured reversibly at approximately 61
      degrees C. In addition, urea denaturation experiments of the wild-type and a
      mutant protein (with 30 additional methionines) confirmed that the structural
      stability of the proteins was very similar. Remarkably, these results indicate
      that the phaseolin protein tolerates extensive modifications, including 20
      substitutions and two loop inserts for methionine enhancement in the beta-barrel
      and loop structures, with extremely small effects on protein stability.

PMID- 8747428
TI  - Conformational changes of alpha-lactalbumin induced by the stepwise reduction of
      its disulfide bridges: the effect of the disulfide bridges on the structural
      stability of the protein in sodium dodecyl sulfate solution.
AB  - Four disulfide bridges of bovine alpha-lactalbumin (alpha-lact) were selectively
      reduced to obtain its derivatives with three, two, and zero disulfide bridges
      (designated as 3SS, 2SS, and 0SS alpha-lact, respectively). The original helicity
      was almost maintained in 3SS alpha-lact missing only the Cys6-Cys120 bridge. Upon
      the reduction of both Cys28-Cys111 and Cys6-Cys120 bridges, various changes
      occurred in the protein. In particular, the maximum fluorescence of 1
      anilinonaphthalene-8-sulfonic acid was observed in this stage. Upon the reduction
      of all disulfide bridges, the hydrophobic box of the protein, formed by Trp60,
      Ile95, Tyr103, and Trp104, was disrupted and an internal helical structure was
      destroyed. The conformation of each derivative was examined mainly in a solution
      of sodium dodecyl sulfate. In the surfactant solution, the helicity increased
      from 33% to 37% in 3SS alpha-lact, from 26% to 31% in 2SS alpha-lact, and from
      18% to 37% in 0SS alpha-lact, as against from 34% to 44% in intact alpha-lact. On
      the other hand, the tryptophan fluorescence of each derivative was affected in
      very low surfactant concentrations, suggesting that the tertiary structure
      considerably changed prior to the secondary structural change in the surfactant
      solution.

PMID- 8747429
TI  - Purification, characterization, sequence determination, and mass spectrometric
      analysis of a trypsin inhibitor from seeds of the Brazilian tree Dipteryx alata
      (Leguminosae).
AB  - Dipteryx alata trypsin inhibitor (DATI) has been purified and completely
      sequenced. It showed homology to members of the Bowman-Birk family of inhibitors.
      The last step of DATI purification by RP-HPLC (narrow-borc C18 column) suggested
      the existence of some isoforms of the inhibitor due to the presence of a cluster
      of very close peaks in the chromatogram. By using electrospray ionization mass
      spectrometry (ESIMS) and laser desorption mass spectrometry (LDIMS), the
      identification of DATI isoforms was made possible. From the ESIMS data, the
      following molecular masses were found: 6803.22 +/- 0.92 for isoform a; 6890.94 +/
      0.73 for b; 6977.58 +/- 0.39 for c; 7065.07 +/- 0.67 for d; 7151.42 +/- 0.86 for
      e; and 7291.70 +/- 0.43 for f. Similar masses were found when using LDIMS.
      Isoform b was the most abundant and its molecular mass matched the molecular mass
      of 6893 calculated from the sequence of DATI. The mass differences between a and
      b, b and c, c and d, and d and e were equal to 87, which corresponds to Ser.
      Isoform a might not have the N-terminal Ser present in isoform b, while the other
      additional Ser residues might comprise a row localized in the C- or N-terminal.
      The appearance of all these isoforms could result from posttranslational N- and C
      terminal processing.

PMID- 8747430
TI  - Kinetics of the course of reactivation of aminoacylase reconstituted using Mn2+
      ions.
AB  - The kinetic theory of the substrate reaction during irreversible change of enzyme
      activity previously described by Tsou [Tsou (1988), Adv. Enzymol Relat. Areas
      Mol. Biol. 61, 381-436] has been applied to a study of the kinetics of the course
      of reactivation during reconstitution of apo-aminoacylase using Mn2+ or Zn2+. The
      kinetic parameters for Mn(2+)- and Zn(2+)-reconstituted enzymes and the
      microscopic rate constants for reactivation during reconstitution were
      determined. The kinetic analysis suggests the presence of a second Mn2+ binding
      site in Mn(2+)-reconstituted aminoacylase.

PMID- 8747431
TI  - Proteolysis of synthetic peptides by type A botulinum neurotoxin.
AB  - Type A botulinum neurotoxin catalyzed the hydrolysis of synthetic peptides based
      on the sequence of the 25-kD synaptosomal protein SNAP-25. In each peptide, the
      toxin cleaved at a single glutaminyl-arginine bond corresponding to residues 197
      and 198 of SNAP-25, confirming earlier reports on the enzymatic specificity of
      the toxin in synaptosomal preparations. Metal chelators inhibited catalysis,
      consistent with a metalloprotease activity. In contrast to tetanus toxin and
      other botulinum toxin serotypes, type A toxin hydrolyzed relatively short, 17- to
      20-residue peptides. In the substrates, SNAP-25 residue 202 and one or more of
      residues 187-191 were required for efficient hydrolysis, but residues 167-186 and
      203-206 were not. The highest rates of hydrolysis were found when the C-terminal
      residues of the peptides were amidated.

PMID- 8747432
TI  - Thermodynamics of denaturation of alpha-chymotrypsinogen A in aqueous urea and
      alkylurea solutions.
AB  - The effects of pH, urea, and alkylureas on the thermal stability of alpha
      chymotrypsinogen A (alpha-ctg A) have been investigated by differential scanning
      calorimetry (DSC) and UV spectroscopy. Heat capacity changes and enthalpies of
      transition of alpha-ctg A in the presence of urea and alkylureas were measured at
      the transition temperature. Using these data, the corresponding Gibbs free
      energies, enthalpies, and entropies of denaturation at 25 degrees C were
      calculated. Comparison of these values shows that at 25 degrees C denaturation
      with urea is characterized by a significantly smaller enthalpy and entropy of
      denaturation. At all denaturant concentrations the enthalpy term slightly
      dominates the entropy term in the Gibbs free energy function. The most obvious
      effect of alkylureas was lowering of the temperature of transition, which was
      increasing with alkylurea concentration and the size of alkyl chain.
      Destabilization of the folded protein in the presence of alkylureas appears to be
      primarily the result of the weakening of hydrophobic interactions due to
      diminished solvent ordering around the protein-molecules. At pH lower than 2.0,
      alpha-ctg A still exists in a very stable form, probably the acid-denatured from
      (A-form).

PMID- 8747433
TI  - Structural effects of the binding of GTP to the wild-type and oncogenic forms of
      the ras-gene-encoded p21 proteins.
AB  - Molecular dynamics calculations have been performed to determine the average
      structures of ras-gene-encoded p21 proteins bound to GTP, i.e., the normal (wild
      type) protein and two oncogenic forms of this protein, the Val 12- and Leu 61-p21
      proteins. We find that the average structures for all of these proteins exhibit
      low coordinate fluctuations (which are highest for the normal protein),
      indicating convergence to specific structures. From previous dynamics
      calculations of the average structures of these proteins bound to GDP, major
      regional differences were found among these proteins [Monaco et al. (1995), J.
      Protein Chem., in press]. We now find that the average structures of the
      oncogenic proteins are more similar to one another when the proteins are bound to
      GTP than when they are bound to GDP [Monaco et al. (1995), J. Protein Chem., in
      press]. However, they still differ in structure at specific amino acid residues
      rather than in whole regions, in contradistinction to the results found for the
      p21-GDP complexes. Two exceptions are the regions 25-32, in an alpha-helical
      region, and 97-110. The two oncogenic (Val 12- and Leu 61-) proteins have similar
      structures which differ significantly in the region of residues 97-110. This
      region has recently been identified as being critical in the interaction of p21
      with kinase target proteins. The differences in structure between the oncogenic
      proteins suggest the existence of more than one oncogenic form of the p21 protein
      that can activate different signaling pathways.

PMID- 8747434
TI  - The superreactive disulfide bonds in alpha-lactalbumin and lysozyme.
AB  - The disulfide reduction kinetics in equine lysozyme (ELZ), which is a Ca(2+)
      binding lysozyme, and human (HLA) and equine alpha-lactalbumin (ELA) at pH 8.5
      and 25 degrees C by excess dithiothreitol were studied, and it was found that in
      ELZ there is no superreactive disulfide bond, while one of the disulfides is
      reduced very quickly by the reducing agent in HLA and ELA, as in bovine alpha
      lactalbumin. The local conformation around the surface disulfide in ELZ seems to
      be more similar to that in hen egg-white lysozyme than in alpha-lactalbumin. The
      four disulfides in ELZ were reduced slowly in an apparently single-exponential
      form, and the bound Ca2+ lowered the reduction rate. The torsion energy on each
      of the disulfides in three alpha-lactalbumin and eight c-type lysozymes whose
      native conformations have been experimentally or theoretically analyzed was
      calculated, and it was found that torsion imposed on the surface disulfide
      between Cys 6 and Cys 120 in alpha-lactalbumin is a main cause of the
      superreactivity and all of lysozymes, including the Ca(2+)-binding ones, have no
      such strained surface bond.

PMID- 8747435
TI  - Fluorescence quenching studies of Trp repressor using single-tryptophan mutants.
AB  - Time-resolved and steady-state fluorescence have been used to resolve the
      heterogeneous emission of single-tryptophan-containing mutants of Trp repressors
      W19F and W99F into components. Using iodide as the quencher, the fluorescence
      quenching-resolved spectra (FQRS) have been obtained The FQRS method shows that
      the fluorescence emission of Trp99 can be resolved into two component spectra
      characterized by maxima of fluorescence emission at 338 and 328 nm. The redder
      component is exposed to the solvent and participates in about 21% of the total
      fluorescence emission of TrpR W19F. The second component is inacessible to
      iodide, but is quenched by acrylamide. The tryptophan residue 19 present in TrpR
      W99F can be resolved into two component spectra using the FQRS method and iodide
      as a quencher. Both components of Trp19 exhibit similar maxima of emission at 322
      324 nm and both are quenchable by iodide. The component more quenchable by iodide
      participates in about 38% of the total TrpR W99F emission. The fluorescence
      lifetime measurements as a function of iodide concentration support the existence
      of two classes of Trp99 and Trp19 in the Trp repressor. Our results suggest that
      the Trp aporepressor can exist in the ground state in two distinct conformational
      states which differ in the microenvironment of the Trp residues.

PMID- 8747436
TI  - Effect of Mg2+ concentrations on phosphorylation/activation of phosphorylase b
      kinase by cAMP/Ca(2+)-independent, autophosphorylation-dependent protein kinase.
AB  - In a previous report [Yu and Yang, Biochem. Biophys. Res. Commun. 207, 140-147
      (1995)], phosphorylase b kinase from rabbit skeletal muscle was found to be
      phosphorylated and activated by a cyclic nucleotide- and Ca(2+)-independent
      protein kinase previously identified as an autophosphorylation-dependent
      multifunctional protein kinase (autokinase) from brain and liver [Yang et al., J.
      Biol. Chem. 262, 7034-7040, 9421-9427 (1987)]. In this report, the effect of Mg2+
      ion concentration on the auto-kinase-catalyzed activation of phosphorylase b
      kinase is investigated. The levels of phosphorylation and activation of
      phosphorylase b kinase catalyzed by auto-kinase are found to be dependent on the
      concentration of Mg2+ ion used. Phosphorylation of phosphorylase b kinase at high
      Mg2+ ion (> 9 mM) is 2-3 times higher than that observed at low Mg2+ ion (1 mM)
      and this results in a further 2- to 3-fold activation of the enzyme activity at
      high Mg2+ ion. Analysis of the phosphorylation stoichiometry of alpha and beta
      subunits of phosphorylase b kinase at different Mg2+ ion concentrations further
      reveals that the phosphorylation level of the beta subunit remains almost
      unchanged, whereas the phosphorylation level of the alpha subunit increases
      dramatically and correlates with the increased enzyme activity. In similarity
      with the beta subunit, phosphorylations of myelin basic protein and histone 2A by
      auto-kinase are also unaffected by Mg2+ ion. Taken together, the results provide
      initial evidence that Mg2+ ion may specifically render the alpha subunit a better
      substrate for auto-kinase to cause further phosphorylation/activation of
      phosphorylase b kinase, representing a new mode of control mechanism for the
      regulation of auto-kinase involved in the phosphorylation and concurrent
      activation of phosphorylase b kinase.

PMID- 8747437
TI  - Structure-function studies of mEGF: probing the type I beta-turn between residues
      25 and 26.
AB  - The interaction between epidermal growth factor (EGF) and its receptor molecule
      is not completely understood and has received much attention recently. Studies
      combining site-directed mutagenesis and NMR spectroscopy have identified a number
      of EGF residues that are required for activity and are believed to interact
      directly with the receptor. Instead of focusing on these residues, this study
      combines site-directed mutagenesis and NMR spectroscopy to probe the role of the
      type I beta-bend located between residues 25 and 26 of the N-terminal subdomain
      of the protein. Ser25 of murine EGF is replaced by Pro in an attempt to stabilize
      this turn conformation to produce a variant of mEGF with increased activity
      relative to that for the native protein. Ser25 is also replaced by Ala, which is
      found at position 25 in human EGF (hEGF), as a more conservative replacement.
      Receptor binding studies demonstrate that both mutations produce about a 30%
      reduction in binding affinity, which is shown to result from local changes within
      the loop or minor perturbations of residues neighboring the loop rather than from
      long-range perturbations of the beta-sheet of the N-terminal subdomain. The type
      I beta-turn appears to remain intact in both mutants; however, replacement with
      Pro seems to introduce more flexibility into this region of the protein. These
      results demonstrate that perturbation of this beta-turn has little effect on EGF
      receptor interactions.

PMID- 8747438
TI  - Intraocular tuberculosis. Clinicopathologic study of five cases.
AB  - BACKGROUND: Intraocular tuberculosis is a rare disease. Only approximately 18
      cases of microbiologically or histopathologically proven cases of intraocular
      tuberculosis have been reported. METHODS: Between 1984 and 1994, five cases of
      intraocular tuberculosis were confirmed microbiologically and histopathologically
      from intraocular specimens in the authors' uveitis clinic. Systemic
      antitubercular treatment was instituted, along with the treatment for the ocular
      inflammation. RESULTS: Clinical presentation included subretinal abscess (two
      cases), granulomatous anterior uveitis with scleral perforation, an exudative
      mass in the anterior chamber, and choroidal mass with panuveitis (one case each).
      Aqueous aspirate in three patients and eviscerated material in the other two
      showed presence of acid fast bacilli. One globe that required enucleation
      revealed granulomatous inflammation with caseation necrosis. Two patients showed
      a significant response to antitubercular therapy, whereas the other three
      patients eventually required evisceration or enucleation. CONCLUSIONS:
      Intraocular tuberculosis can have protean manifestations and variable response to
      systemic antitubercular therapy.

PMID- 8747439
TI  - Vitrectomy alone for the management of uncomplicated recurrent retinal
      detachments.
AB  - BACKGROUND: The role of vitrectomy for the treatment of uncomplicated recurrent
      retinal detachments has not been defined clearly. The authors report their
      experience with vitrectomy alone for the management of such cases. METHODS: Pars
      plana vitrectomy with internal subretinal fluid drainage and long-term tamponade
      was performed on nine patients with uncomplicated recurrent retinal detachments
      after primary scleral buckling surgery. The duration of follow-up was a minimum
      of 6 months (mean, 39 months). RESULTS: Anatomic success was achieved after the
      initial reoperation in seven eyes (78%). The overall success rate was 89%. The
      visual acuity was 20/30 or better in three patients, 20/ 40 to 20/80 in three
      patients, and 20/200 in two patients. Complications included progressive nuclear
      sclerosis and macular pucker. CONCLUSION: Vitrectomy is effective and may have
      advantages over other methods for the management of uncomplicated recurrent
      retinal detachments.

PMID- 8747440
TI  - Macular edema in chronic Vogt-Koyanagi-Harada syndrome.
AB  - BACKGROUND: Macular edema is relatively rare in the Vogt-Koyanagi-Harada (VKH)
      syndrome, in contrast to many other syndromes of chronic intraocular
      inflammation, in which macular edema is relatively common. Five eyes of three
      patients with chronic VKH syndrome and macular edema are described. METHODS: The
      authors retrospectively reviewed the clinical and fluorescein angiographic
      records of 27 patients with chronic VKH syndrome (duration of disease more than 3
      months) and identified three patients (five eyes) who had macular edema.
      Fluorescein angiography was performed using a scanning laser ophthalmoscope.
      RESULTS: These patients had either unusually severe and protracted inflammation
      (3 eyes) of the presence of an epiretinal membrane (2 eyes). Fluorescein
      angiography demonstrated prominent perifoveal fluorescein leakage with pooling of
      fluorescein within perifoveal cystoid spaces. Treatment with sub-Tenon's
      triamcinolone injections resulted in improvement of visual acuity by two or more
      Snellen lines in four of the five eyes. CONCLUSION: Macular edema is an uncommon
      but treatable cause of late loss of vision in patients with the VKH syndrome, and
      may be the result of leakage from perifoveal retinal capillaries or leakage of
      fluid at the level of the retinal pigment epithelium.

PMID- 8747441
TI  - Sorsby's fundus dystrophy. A South African family with a point mutation on the
      tissue inhibitor of metalloproteinases-3 gene on chromosome 22.
AB  - PURPOSE: The authors studied the variable expressivity of the phenotype and
      molecular genetics of a South African family with the fundus appearance of
      Sorsby's fundus dystrophy. METHODS: Seventeen members of a single family
      underwent examination. Five of these were affected. Clinical details of five
      other affected family members were obtained from their ophthalmologists. Patients
      were questioned about age of onset, history of night blindness, and color
      defects. Examination included fundoscopy, color testing, color photographs, and
      fluorescein angiography. Blood for molecular genetic analysis was taken from 23
      family members. RESULTS: The age of onset of symptoms was 29 to 56 years, and the
      rate of progression was variable. Sudden decreased vision was associated with
      subretinal choroidal neovascularization. Slower visual decline was associated
      with central chorioretinal atrophy. Progressive retinal pigment epithelial
      atrophy and peripheral pigment clumping occurred in elderly relatives who lost
      ambulatory vision. DNA studies show linkage to the long arm of chromosome 22 and
      a point mutation in the tissue inhibitor of metalloproteinases-3 gene.
      CONCLUSION: This South African family presents with a dominantly inherited fundus
      dystrophy with clinical and molecular features compatible with Sorsby's fundus
      dystrophy.

PMID- 8747442
TI  - Threshold retinopathy of prematurity. Transition from cryopexy to laser
      treatment.
AB  - PURPOSE: The authors studied the effectiveness of laserpexy versus cryopexy for
      treatment of acute retinopathy of prematurity. METHODS: Seventy-six eyes in 41
      patients were treated for acute retinopathy of prematurity from January 1991 to
      April 1994. RESULTS: Fifty-six eyes in 30 patients had zone 2 disease. Of these
      30 patients, 11 received laser treatment and 20 received cryopexy treatment;
      there was at least one anatomically successful eye in each patient. Twenty eyes
      in ten patients had zone 1 disease. Seven patients had bilateral laser treatment.
      Three patients had bilateral cryopexy. In seven eyes with zone 1 disease, five
      were treated successfully with laser. None of the three eyes with zone 1 disease
      treated with cryopexy were successful. CONCLUSION: Laserpexy and cryopexy are of
      equal efficacy in treating zone 2 disease. There is a tendency that suggests that
      laserpexy is more effective than cryopexy in treating zone 1 disease. Diode and
      argon lasers are of equal efficacy in treating zone 1 disease.

PMID- 8747443
TI  - A numeric index based on spatial frequency for the tortuosity of retinal vessels
      and its application to plus disease in retinopathy of prematurity.
AB  - BACKGROUND: In retinopathy of prematurity (ROP), tortuosity of vessels near the
      posterior pole of the fundus is an important clinical sign, yet clinicians have
      difficulty estimating how tortuous the vessels are. METHODS: The authors have
      devised an objective, numeric index of retinal blood vessel tortuosity that is
      especially sensitive to the structural changes in vessels that occur in ROP, but
      it is not particularly sensitive to non-ROP changes. Computer software is used to
      calculate the index from fundus images; the quality of these images is typical of
      photographs or video-cassette frames that the authors record in the premature
      nursery. RESULTS: The index reliably segregates tortuous vessels from nontortuous
      ones and separates eyes that reach ROP treatment threshold from eyes that do not.
      CONCLUSIONS: The index forms an objective measure of the ROP disease state. Its
      calculation requires only segments of vessels and thus, is potentially adaptable
      to imaging systems that automatically extract vessel portions from fundus images.

PMID- 8747444
TI  - Cilioretinal artery occlusion in sickle cell trait and rheumatoid arthritis.
AB  - BACKGROUND: Although once thought to be a benign condition, retinal vascular
      occlusive disease and proliferative retinopathy can occur with sickle cell trait
      (hemoglobin AS) when additional systemic diseases or trauma are present. METHODS:
      The authors discuss the ophthalmologic evaluation and clinical course of a 49
      year-old woman with sickle cell trait and rheumatoid arthritis who presented with
      a cilioretinal artery occlusion. RESULTS: The patient's laboratory evaluation
      showed both a high rheumatoid factor titer and a mild hypergammaglobulinemia,
      causing increased serum viscosity. The high level of sickle hemoglobin-42.3%
      (range in trait, 22%-46%)-increased serum viscosity, and lower cilioretinal
      artery perfusion pressure relative to the central retinal artery resulted in
      cilioretinal artery occlusion. CONCLUSIONS: Isolated cilioretinal artery
      occlusions carry a good prognosis, and this patient recovered 20/20 visual acuity
      in the affected eye. The association between sickle cell trait and rheumatoid
      arthritis resulting in retinal vascular occlusive disease has not been reported
      previously. The presence of retinal vascular occlusion in sickle cell trait
      necessitates a medical evaluation for additional systemic diseases.

PMID- 8747445
TI  - Vitreous observation using a CCD camera and a computerized unit for image
      processing and storage.
AB  - PURPOSE: This study was conducted to evaluate a new technique of vitreous
      observation. METHODS: The authors used commercially available devices, including
      a slit-lamp, monochromatic charge coupled device (CCD) camera, and a computerized
      unit for image processing and storage, to observe the vitreous and the
      vitreoretinal relationship. RESULTS: The authors obtained good images of the
      vitreous and the vitreoretinal relationship using the new technique. Furthermore,
      the image stored in the computer could be accessed and used for patient
      explanations instantly. CONCLUSION: This technique is useful for documenting the
      vitreous and can help determine the role of the vitreous in many vitreoretinal
      disorders.

PMID- 8747446
TI  - Biomicroscopic vitreous videography.
AB  - PURPOSE: The authors report on the technique of biomicroscopic vitreous
      videography using the recently developed charge coupled device (CCD) video
      camera. METHODS: The authors performed biomicroscopic vitreous videography using
      the CCD video camera connected to a slit-lamp biomicroscope to examine 50 eyes
      with age- or disease-related vitreous changes in 50 patients. The cases were
      categorized as follows: 20 normal senile eyes; 10 eyes with retinal breaks; 10
      eyes with diabetic retinopathy; 5 eyes with uveitis; and 5 eyes with high myopia.
      Noncontact positive preset lenses were used for observing the posterior vitreous;
      a wide-angle funduscopic contact lens and a three-mirror contact lens were used
      to observe the peripheral vitreoretinal changes. RESULTS: Using the CCD video
      camera, dynamic vitreous changes were documented clearly using real-time
      television monitoring. The video system also allowed rapid review of the vitreous
      changes. CONCLUSION: This new biomicroscopic vitreous videography system will
      contribute to the study of vitreoretinal diseases and be valuable as an
      educational tool.

PMID- 8747447
TI  - Effect of partial retinal destruction and gliosis on the intravitreal
      pharmacokinetics of HPMPC.
AB  - PURPOSE: Intravitreal HPMPC ([S]-1-[3-hydroxy-2 phosphonylmethoxypropyl cytosine)
      has a long antiviral effect in patients with cytomegalovirus retinitis. The
      authors evaluated the pharmacokinetics of intravitreal injections of HPMPC to
      understand major route of HPMPC elimination in a pigmented rabbit that had
      undergone scatter laser photocoagulation over half of the retinal surface.
      METHODS: The authors treated the inferior half of the retina, receiving an
      average of 605 grade 3 or 4 (gray-white or white) diode laser burns in a scatter
      fashion in the left eyes of 13 rabbits. After 4 weeks, 13 rabbits received
      intravitreal injection of HPMPC (100 micrograms in 0.1 mL) in both eyes. Forty
      eight hours after injection, unfixed vitreous samples were obtained for high
      pressure liquid chromatography analysis. Two rabbits were used for light
      microscopic examination of diode laser photocoagulated retina with the perfusion
      fixation. RESULTS: The HPMPC concentration in the vitreous was 5.93 +/- 1.75
      micrograms/mL in the laser-treated group and 4.76 +/- 1.2 micrograms/mL in the
      control group 48 hours after intravitreal HPMPC injection. The difference was
      statistically different (P = 0.037). CONCLUSIONS: Results showed a higher
      concentration of intravitreal HPMPC in the eye that had approximately 25% of the
      retina destroyed by the laser photocoagulation. The higher concentration is
      likely the result of reduced elimination and a concomitant increase in half-life.
      This suggests that HPMPC may be eliminated via the retinal route. Eyes with more
      extensive retinal involvement with human cytomegalovirus may have an even longer
      duration of action of intravitreal HPMPC. This may lead to modification of dosing
      regimens.

PMID- 8747448
TI  - Macular dystrophy associated with monogenic Arg172Trp mutation of the
      peripherin/RDS gene in a Japanese family.
AB  - OBJECTIVE: Mutations of the peripherin/RDS gene have been reported in several
      kinds of retinal dystrophy, and they show variation of manifestation. In some
      pedigrees, the same mutation can produce different phenotypic features, a factor
      that makes it difficult to deduce certain rules for genotype-phenotype
      correlations in the peripherin/RDS gene. The authors report the phenotypic
      features of a Japanese family with a mutation in codon 172 of the peripherin/RDS
      gene and compare them to previously reported ocular findings in British pedigrees
      with the same mutation. PATIENTS AND METHODS: A 45-year-old man and his 15-year
      old son were screened for mutations in the peripherin/RDS gene and the ROM1 gene.
      Clinical features were characterized by visual acuity and visual field testing,
      fundus examination, fluorescein angiography, and electroretinography. RESULTS:
      Both patients had the same mutation in codon 172 of the peripherin/RDS gene
      designated as Arg172Trp. No mutation was found in the ROM1 gene in either
      patient. Clinical features were summarized as autosomal dominant macular
      dystrophy. The father had sharply demarcated chorioretinal atrophy in the macula.
      The son showed mild granularity in the macular area in ophthalmoscopic
      appearances. CONCLUSIONS: The Arg172Trp mutation was confirmed to produce
      autosomal dominant macular dystrophy. This particular phenotype was caused by the
      monogenic mutation in the peripherin/RDS gene.

PMID- 8747449
TI  - Retinal detachment in acute systemic hypertension.

PMID- 8747450
TI  - An illuminated fork retractor for retinal detachment and orbital surgery.

PMID- 8747451
TI  - Use of the potential acuity meter and laser interferometer to predict visual
      acuity after macular hole surgery.

PMID- 8747452
TI  - How to make my blood boil.
AB  - Two recent papers comparing the structure of a hyperthermophilic protein with its
      mesophilic counterpart both conclude that large networks of ion-pairs are
      important for hyperthermostability. How and why is not yet clear.

PMID- 8747453
TI  - Switching to Rac and Rho.
AB  - Could the recent elucidation of the structure of the Rap-Raf complex have been
      the first glimpse of a universal arrangement between GTPase switches and kinase
      cascades, as a number of recent reports show that Ras is not unique in its
      ability to start a signalling 'chain reaction'?

PMID- 8747454
TI  - The enigma of LIM domains.
AB  - LIM domains are two-zinc-finger structures found in proteins that have diverse
      functions. They are proposed to be protein dimerization motifs that assemble
      protein complexes necessary for growth, development and adaptive responses.

PMID- 8747455
TI  - The use of antibody fragments for crystallization and structure determinations.

PMID- 8747456
TI  - 2.0 A structure of indole-3-glycerol phosphate synthase from the hyperthermophile
      Sulfolobus solfataricus: possible determinants of protein stability.
AB  - BACKGROUND: Recent efforts to understand the basis of protein stability have
      focused attention on comparative studies of proteins from hyperthermophilic and
      mesophilic organisms. Most work to date has been on either oligomeric enzymes or
      monomers comprising more than one domain. Such studies are hampered by the need
      to distinguish between stabilizing interactions acting between subunits or
      domains from those acting within domains. In order to simplify the search for
      determinants of protein stability we have chosen to study the monomeric enzyme
      indole-3-glycerol phosphate synthase from the hyperthermophilic archaeon
      Sulfolobus solfataricus (sIGPS), which grows optimally at 90 degrees C. RESULTS:
      The 2.0 A crystal structure of sIGPS was determined and compared with the known
      2.0 A structure of the IGPS domain of the bifunctional enzyme from the mesophilic
      bacterium Escherichia coli (eIGPS). sIGPS and eIGPS have only 30% sequence
      identity, but share high structural similarity. Both are single-domain
      (beta/alpha)8 barrel proteins, with one (eIGPS) or two (sIGPS) additional helices
      inserted before the first beta strand. The thermostable sIGPS has many more salt
      bridges than eIGPS. Several salt bridges crosslink adjacent alpha helices or
      participate in triple or quadruple salt-bridge clusters. The number of helix
      capping, dipole stabilizing and hydrophobic interactions is also increased in
      sIGPS. CONCLUSIONS: The higher stability of sIGPS compared with eIGPS seems to be
      the result of several improved interactions. These include a larger number of
      salt bridges, stabilization of alpha helices and strengthening of both
      polypeptide chain termini and solvent-exposed loops.

PMID- 8747457
TI  - X-ray structure of human nucleoside diphosphate kinase B complexed with GDP at 2
      A resolution.
AB  - BACKGROUND: Nucleoside diphosphate (NDP) kinases provide precursors for DNA and
      RNA synthesis. In mammals, these enzymes are also involved in cell regulations.
      Human NDP kinase B, product of the human nm23-H2 gene, is both an enzyme and a
      transcription factor. It activates transcription of the c-myc oncogene
      independently of its catalytic function, by binding to its promoter DNA. How do
      the two functions coexist? RESULTS: Recombinant human NDP kinase B was co
      crystallized with GDP. The X-ray structure was solved at 2.0 A resolution by
      molecular replacement from the homologous Drosophila Awd protein. Both enzymes
      are homo-hexamers with a characteristic beta alpha beta beta alpha beta fold. GDP
      binds near the active site His118. The guanine base is in a surface cleft and
      interacts with the C terminus of another subunit. CONCLUSIONS: The beta alpha
      beta beta alpha beta fold, also present in the 'palm' domain of Escherichia coli
      DNA polymerase I and HIV reverse transcriptase, is both a mononucleotide- and a
      polynucleotide-binding fold. If NDP kinase B binds DNA in the same way as the
      polymerases, the enzyme must undergo a conformation change in order to carry out
      gene activation.

PMID- 8747458
TI  - A 26 kDa yeast DNA topoisomerase I fragment: crystallographic structure and
      mechanistic implications.
AB  - BACKGROUND: Type I DNA topoisomerases, divided mechanistically into two
      subfamilies, are ubiquitous enzymes that participate in replication and
      transcription. In addition to its role in these fundamental processes, the
      biological importance of eukaryotic DNA topoisomerase I is underscored by its
      identification as the target of the antitumor alkaloid camptothecin. An
      understanding of the mechanism of catalysis and interactions with camptothecin
      and other drugs has been hampered by a lack of detailed structural information.
      RESULTS: The three-dimensional structure of a 26 kDA fragment (residues 135 to
      about 363) of Saccharomyces cerevisiae DNA topoisomerase I has been determined at
      1.9 A resolution. The fragment has a novel architecture comprising a concave
      platform and a pair of outlying V-shaped helices. Photocrosslinking and protein
      footprinting experiments show that the positively charged concave surface and the
      junction region of the V-shaped pair of helices contact DNA in the enzyme-DNA
      complex. CONCLUSIONS: Crystallographic, biochemical and genetic data indicate
      that this 26 kDa fragment of yeast DNA topoisomerase I is involved in complex
      formation between the enzyme and DNA, and probably also in camptothecin-enzyme
      DNA ternary complex formation. A molecular model for protein-DNA interaction
      based on these data is proposed. The bipartite DNA-binding regions of the 26 kDa
      fragment may enable eukaryotic DNA topoisomerase I to adapt to sequence-dependent
      structural variations in its DNA substrates.

PMID- 8747459
TI  - Structure and catalytic mechanism of glucosamine 6-phosphate deaminase from
      Escherichia coli at 2.1 A resolution.
AB  - BACKGROUND: Glucosamine 6-phosphate deaminase from Escherichia coli is an
      allosteric hexameric enzyme which catalyzes the reversible conversion of D
      glucosamine 6-phosphate into D-fructose 6-phosphate and ammonium ion and is
      activated by N-acetyl-D-glucosamine 6-phosphate. Mechanistically, it belongs to
      the group of aldoseketose isomerases, but its reaction also accomplishes a
      simultaneous amination/deamination. The determination of the structure of this
      protein provides fundamental knowledge for understanding its mode of action and
      the nature of allosteric conformational changes that regulate its function.
      RESULTS: The crystal structure of glucosamine 6-phosphate deaminase with bound
      phosphate ions is presented at 2.1 A resolution together with the refined
      structures of the enzyme in complexes with its allosteric activator and with a
      competitive inhibitor. The protein fold can be described as a modified NAD
      binding domain. CONCLUSIONS: From the similarities between the three presented
      structures, it is concluded that these represent the enzymatically active R state
      conformer. A mechanism for the deaminase reaction is proposed. It comprises steps
      to open the pyranose ring of the substrate and a sequence of general base
      catalyzed reactions to bring about isomerization and deamination, with Asp72
      playing a key role as a proton exchanger.

PMID- 8747460
TI  - Two conformations of the integrin A-domain (I-domain): a pathway for activation?
AB  - BACKGROUND: Integrins are plasma membrane proteins that mediate adhesion to other
      cells and to components of the extracellular matrix. Most integrins are
      constitutively inactive in resting cells, but are rapidly and reversibly
      activated in response to agonists, leading to highly regulated cell adhesion.
      This activation is associated with conformational changes in their extracellular
      portions, but the nature of the structural changes that lead to a change in
      adhesiveness is not understood. The interactions of several integrins with their
      extracellular ligands are mediated by an A-type domain (generally called the I
      domain in integrins). Binding of the I-domain to protein ligands is dependent on
      divalent cations. We have described previously the structure of the I-domain from
      complement receptor 3 with bound Mg2+, in which the glutamate side chain from a
      second I-domain completes the octahedral coordination sphere of the metal, acting
      as a ligand mimetic. RESULTS: We now describe a new crystal form of the I-domain
      with bound Mn2+, in which water completes the metal coordination sphere and there
      is no equivalent of the glutamate ligand. Comparison of the two crystal forms
      reveals a change in metal coordination which is linked to a large (10 A) shift of
      the C-terminal helix and the burial of two phenylalanine residues into the
      hydrophobic core of the Mn2+ form. These structural changes, analogous to those
      seen in the signal-transducing G-proteins, alter the electrophilicity of the
      metal, reducing its ability to bind ligand-associated acidic residues, and
      dramatically alter the surface of the protein implicated in binding ligand.
      CONCLUSIONS: Our observations provide the first atomic resolution view of
      conformational changes in an integrin domain, and suggest how these changes are
      linked to a change in integrin adhesiveness. We propose that the Mg2+ form
      represents the conformation of the domain in the active state and the Mn2+ form
      the conformation in the inactive state of the integrin.

PMID- 8747461
TI  - Structural predictions for the ligand-binding region of glycoprotein hormone
      receptors and the nature of hormone-receptor interactions.
AB  - BACKGROUND: Glycoprotein hormones influence the development and function of the
      ovary, testis and thyroid by binding to specific high-affinity receptors. The
      extracellular domains of these receptors are members of the leucine-rich repeat
      (LRR) protein superfamily and are responsible for the high-affinity binding. The
      crystal structure of a glycoprotein hormone, namely human choriogonadotropin
      (hCG), is known, but neither the receptor structure, mode of hormone binding, nor
      mechanism for activation, have been established. RESULTS: Despite very low
      sequence similarity between exon-demarcated LRRs in the receptors and the LRRs of
      porcine ribonuclease inhibitor (RI), the secondary structures for the two repeat
      sets are found to be alike Constraints on curvature and beta-barrel geometry from
      the sequence pattern for repeated beta alpha units suggest that the receptors
      contain three-dimensional structures similar to that of RI. With the RI crystal
      structure as a template, models were constructed for exons 2-8 of the receptors.
      The model for this portion of the choriogonadotropin receptor is complementary in
      shape and electrostatic characteristics to the surface of hCG at an identified
      focus of hormone-receptor interaction. CONCLUSIONS: The predicted models for the
      structures and mode of hormone binding of the glycoprotein hormone receptors are
      to a large extent consistent with currently available biochemical and mutational
      data. Repeated sequences in beta-barrel proteins are shown to have general
      implications for constraints on structure. Averaging techniques used here to
      recognize the structural motif in these receptors should also apply to other
      proteins with repeated sequences.

PMID- 8747462
TI  - Crystal structure of an acetylcholinesterase-fasciculin complex: interaction of a
      three-fingered toxin from snake venom with its target.
AB  - BACKGROUND: Fasciculin (FAS), a 61-residue polypeptide purified from mamba venom,
      is a three-fingered toxin which is a powerful reversible inhibitor of
      acetylcholinesterase (AChE). Solution of the three-dimensional structure of the
      AChE/FAS complex would provide the first structure of a three-fingered toxin
      complexed with its target. RESULTS: The structure of a complex between Torpedo
      californica AChE and fasciculin-II (FAS-II), from the venom of the green mamba
      (Dendroaspis angusticeps) was solved by molecular replacement techniques, and
      refined at 3.0 A resolution to an R-factor of 0.231. The structure reveals a
      stoichiometric complex with one FAS molecule bound to each AChE subunit. The AChE
      and FAS conformations in the complex are very similar to those in their isolated
      structures. FAS is bound at the 'peripheral' anionic site of AChE, sealing the
      narrow gorge leading to the active site, with the dipole moments of the two
      molecules roughly aligned. The high affinity of FAS for AChE is due to a
      remarkable surface complementarity, involving a large contact area (approximately
      2000 A2) and many residues either unique to FAS or rare in other three-fingered
      toxins. The first loop, or finger, of FAS reaches down the outer surface of the
      thin aspect of the gorge. The second loop inserts into the gorge, with an unusual
      stacking interaction between Met33 in FAS and Trp279 in AChE. The third loop
      points away from the gorge, but the C-terminal residue makes contact with the
      enzyme. CONCLUSIONS: Two conserved aromatic residues in the AChE peripheral
      anionic site make important contacts with FAS. The absence of these residues from
      chicken and insect AChEs and from butyrylcholinesterase explains the very large
      reduction in the affinity of these enzymes for FAS. Several basic residues in FAS
      make important contacts with AChE. The complementarity between FAS and AChE is
      unusual, inasmuch as it involves a number of charged residues, but lacks any
      intermolecular salt linkages.

PMID- 8747463
TI  - The crystal structure of chloroperoxidase: a heme peroxidase--cytochrome P450
      functional hybrid.
AB  - BACKGROUND: Chloroperoxidase (CPO) is a versatile heme-containing enzyme that
      exhibits peroxidase, catalase and cytochrome P450-like activities in addition to
      catalyzing halogenation reactions. The structure determination of CPO was
      undertaken to help elucidate those structural features that enable the enzyme to
      exhibit these multiple activities. RESULTS: Despite functional similarities with
      other heme enzymes, CPO folds into a novel tertiary structure dominated by eight
      helical segments. The catalytic base, required to cleave the peroxide O-O bond,
      is glutamic acid rather than histidine as in other peroxidases. CPO contains a
      hydrophobic patch above the heme that could be the binding site for substrates
      that undergo P450-like reactions. The crystal structure also shows extensive
      glycosylation with both N- and O-linked glycosyl chains. CONCLUSIONS: The
      proximal side of the heme in CPO resembles cytochrome P450 because a cysteine
      residue serves as an axial heme ligand, whereas the distal side of the heme is
      'peroxidase-like' in that polar residues form the peroxide-binding site. Access
      to the heme pocket is restricted to the distal face such that small organic
      substrates can interact with the iron-linked oxygen atom which accounts for the
      P450-like reactions catalyzed by chloroperoxidase.

PMID- 8747464
TI  - Crystal structure of human Charcot-Leyden crystal protein, an eosinophil
      lysophospholipase, identifies it as a new member of the carbohydrate-binding
      family of galectins.
AB  - BACKGROUND: The Charcot-Leyden crystal (CLC) protein is a major autocrystallizing
      constituent of human eosinophils and basophils, comprising approximately 10% of
      the total cellular protein in these granulocytes. Identification of the
      distinctive hexagonal bipyramidal crystals of CLC protein in body fluids and
      secretions has long been considered a hallmark of eosinophil-associated allergic
      inflammation. Although CLC protein possesses lysophospholipase activity, its
      role(s) in eosinophil or basophil function or associated inflammatory responses
      has remained speculative. RESULTS: The crystal structure of the CLC protein has
      been determined at 1.8 A resolution using X-ray crystallography. The overall
      structural fold of CLC protein is highly similar to that of galectins -1 and -2,
      members of an animal lectin family formerly classified as S-type or S-Lac
      (soluble lactose-binding) lectins. This is the first structure of an eosinophil
      protein to be determined and the highest resolution structure so far determined
      for any member of the galectin family. CONCLUSIONS: The CLC protein structure
      possesses a carbohydrate-recognition domain comprising most, but not all, of the
      carbohydrate-binding residues that are conserved among the galectins. The protein
      exhibits specific (albeit weak) carbohydrate-binding activity for simple
      saccharides including N-acetyl-D-glucosamine and lactose. Despite CLC protein
      having no significant sequence or structural similarities to other
      lysophospholipase catalytic triad has also been identified within the CLC
      structure, making it a unique dual-function polypeptide. These structural
      findings suggest a potential intracellular and/or extracellular role(s) for the
      galectin-associated activities of CLC protein in eosinophil and basophil function
      in allergic diseases and inflammation.

PMID- 8747465
TI  - The crystal structures of the oligopeptide-binding protein OppA complexed with
      tripeptide and tetrapeptide ligands.
AB  - BACKGROUND: The periplasmic oligopeptide-binding protein OppA has a remarkably
      broad substrate specificity, binding peptides of two or five amino-acid residues
      with high affinity, but little regard to sequence. It is therefore an ideal
      system for studying how different chemical groups can be accommodated in a
      protein interior. The ability of the protein to bind peptides of different
      lengths has been studied by co-crystallising it with different ligands. RESULTS:
      Crystals of OppA from Salmonella typhimurium complexed with the peptides Lys-Lys
      Lys (KKK) and Lys-Lys-Lys-Ala (KKKA) have been grown in the presence of uranyl
      ions which form important crystal contacts. These structures have been refined to
      1.4 A and 2.1 A, respectively. The ligands are completely enclosed, their side
      chains pointing into large hydrated cavities and making few strong interactions
      with the protein. CONCLUSIONS: Tight peptide binding by OppA arises from strong
      hydrogen bonding and electrostatic interactions between the protein and the main
      chain of the ligand. Different basic side chains on the protein form salt bridges
      with the C terminus of peptide ligands of different lengths.

PMID- 8747466
TI  - Structure of the biotinyl domain of acetyl-coenzyme A carboxylase determined by
      MAD phasing.
AB  - BACKGROUND: Acetyl-coenzyme A carboxylase catalyzes the first committed step of
      fatty acid biosynthesis. Universally, this reaction involves three functional
      components all related to a carboxybiotinyl intermediate. A biotinyl domain
      shuttles its covalently attached biotin prosthetic group between the active sites
      of a biotin carboxylase and a carboxyl transferase. In Escherichia coli, the
      three components reside in separate subunits: a biotinyl domain is the functional
      portion of one of these, biotin carboxy carrier protein (BCCP). RESULTS: We have
      expressed natural and selenomethionyl (Se-met) BCCP from E. coli as biotinylated
      recombinant proteins, proteolyzed them with subtilisin Carlsberg to produce the
      biotinyl domains BCCP and Se-met BCCPsc, determined the crystal structure of Se
      met BCCPsc using a modified version of the multiwavelength anomalous diffraction
      (MAD) phasing protocol, and refined the structure for the natural BCCPsc at 1.8 A
      resolution. The structure may be described as a capped beta sandwich with quasi
      dyad symmetry. Each half contains a characteristic hammerhead motif. The
      biotinylated lysin is located at a hairpin beta turn which connects the two
      symmetric halves of the molecule, and its biotinyl group interacts with a non
      symmetric protrusion from the core. CONCLUSIONS: This first crystal structure of
      a biotinyl domain helps to unravel the central role of such domains in reactions
      catalyzed by biotin-dependent carboxylases. The hammerhead structure observed
      twice in BCCPsc may be regarded as the basic structural motif of biotinyl and
      lipoyl domains of a superfamily of enzymes. The new MAD phasing techniques
      developed in the course of determining this structure enhance the power of the
      MAD method.

PMID- 8747467
TI  - New guidelines for deposition of nucleic acid structures.

PMID- 8747468
TI  - 2 A crystal structure of an extracellular fragment of human CD40 ligand.

PMID- 8747469
TI  - Determination of free and liposome-associated doxorubicin and vincristine levels
      in plasma under equilibrium conditions employing ultrafiltration techniques.
AB  - A thorough understanding of the pharmacodynamic relationships associated with
      toxicity and efficacy behavior of liposome-encapsulated anticancer agents such as
      doxorubicin and vincristine will rely on the ability to accurately separate and
      quantify the free and liposome-associated drug fractions in plasma after
      administration. We have investigated the use of ultrafiltration as a method of
      isolating free doxorubicin and vincristine from liposomal drug under equilibrium
      conditions and compared it to previously developed nonequilibrium procedures
      based on solid-phase extraction. Adsorption of drugs dissolved in saline to the
      ultrafiltration devices resulted in concentration-dependent ultrafiltrate drug
      recoveries ranging from 41 to 96%. However, concentration-independent
      quantitative recovery of vincristine in saline solutions could be obtained by
      passivating the ultrafiltration devices with PEG-8000 and device drug adsorption
      was ameliorated for both agents by plasma. The ultrafiltration method provided a
      more reliable separation of free and protein-bound drug, whereas solid-phase
      extraction yielded artificially high free drug concentrations due to process
      induced protein-bound drug complex dissocation. Also, coelution of liposomes with
      the free drug fraction using solid-phase extraction was 64- to 418-fold higher
      than observed with ultrafiltration. Taken together, these properties indicated a
      significantly increased degree of accuracy in measuring the amount of free
      doxorubicin and vincristine in samples containing liposomal formulations
      employing ultrafiltration compared to solid-phase extraction. The importance of
      this improvement was highlighted by observations that determinations of free drug
      concentrations in the plasma of mice injected with liposomal doxorubicin and
      vincristine were 3- to 12-fold higher using solid-phase extraction compared to
      ultrafiltration. Finally, the ultrafiltration procedure is rapid, versatile, and
      can be used for a wide range of drug and liposome concentrations and free
      drug/liposomal drug ratios.

PMID- 8747470
TI  - Direct measurement of crosslinks, pyridinoline, deoxypyridinoline, and
      pentosidine, in the hydrolysate of tissues using high-performance liquid
      chromatography.
AB  - Pyridinoline (Pyr) and deoxypyridinoline (Dpyr) are mature crosslinks which
      maintain the structure of the collagen fibril. Pentosidine (Pen) is a senescent
      crosslink and one of the advanced glycation end products. We developed a direct
      and one-injection method to measure Pyr, Dpyr, and Pen in the hydrolysate of
      tissues using reversed-phase high-performance liquid chromatography. Using a
      linear gradient of acetonitrile and a cleaning step, the objective crosslinks
      were well separated and continuously and automatically assayed. Recovery rates of
      Pyr, Dpyr, and Pen were 95-116, 94-110, and 92-120%, respectively (n = 5). The
      intraassay coefficients of variation for Pyr, Dpyr, and Pen were 5.3, 5.8, and
      4.3%, respectively (n = 5), and the interassay coefficients of variation for Pyr,
      Dpyr, and Pen were 3.5, 4.6, and 5.7%, respectively (n = 5). Linear regression
      analysis showed the linearity (r = 0.999) of calibration line for each Pyr, Dpyr,
      and Pen. We measured the content of these crosslinks in the tissues from the
      young and old subjects. There was no difference in the content of Pyr and Dpyr
      between the young and the old group. On the other hand, the content of Pen in the
      old group was extremely higher than that in the young group. We demonstrated the
      direct method for measuring two kinds of major crosslinks which have different
      characters and believe that this method will be useful in determining the content
      of these crosslinks in tissues under various conditions.

PMID- 8747471
TI  - Anion-exchange high-performance liquid chromatographic assay of plasma
      lipoproteins.
AB  - A fast, accurate, and precise high-performance liquid chromatographic (HPLC)
      assay method for human plasma lipoproteins has been developed. The method
      includes complete separation of high-, low-, and very-low-density lipoproteins
      within 20 min using a DEAE-glucomannan gel with stepwise elution, enzymatic
      oxidation of cholesterol (following ester hydrolysis) followed by a two-step
      reaction to form a fluorogenic product, and fluorometric detection as the total
      cholesterol (TC) level of each lipoprotein. The calibration range is 5-1000
      micrograms/ml for the TC level of 20-microliters plasma samples and the relative
      standard deviation (n = 5) of the precision at 5 micrograms/ml is less than 10%.
      Each lipoprotein level determined by this optimized HPLC method agrees well with
      levels determined by ultracentrifugation or precipitation methods. This new
      method was successfully applied to assays of plasma lipoproteins in various forms
      of hyperlipidemia.

PMID- 8747472
TI  - Quantitative determination of DNA-binding parameters for the human estrogen
      receptor in a solid-phase, nonseparation assay.
AB  - Binding of transcription factors to specific sequences of DNA has been studied
      for more than a decade and has become a very productive field of research. This
      paper describes the application of the recently developed technique of
      scintillating microtitration plates in the study of protein-DNA interactions. A
      DNA sequence containing the classical consensus estrogen response element derived
      from the 5' upstream regulatory region of the frog vitellogenin gene was
      immobilized to scintillating microtitration plates. Equilibrium binding studies
      and kinetic studies were performed with [3H] estradiol labeled human estrogen
      receptor. The observed equilibrium dissociation constant (Kd) was 2.0 +/- 0.3 nM
      and the observed Hill coefficient of 2.0 indicated a positive cooperativity. Two
      association rate constants were observed, one slower of 0.3 x 10(6) M-1 min-1 for
      lower concentrations of estrogen receptor and one faster of 6.3 x 10(6) M-1 min-1
      for higher concentrations. The dissociation rate was 0.005 min-1. The technique
      described has a potential in basic research concerning characterization of DNA
      binding. It is also well suited to applied research as a tool in high-throughput
      screening of compound libraries in the search of agents inhibiting transcription
      factor binding to DNA.

PMID- 8747474
TI  - Thermodynamic analysis of tetracycline-mediated induction of Tet repressor by a
      quantitative methylation protection assay.
AB  - We describe a method for quantitative detection and thermodynamic interpretation
      of tetracycline (tc)-mediated induction of the Tn10 encoded Tet repressor (TetR).
      Binding of dimeric TetR to the tet operator (tetO) was quantitated by protection
      of DNA from methylation as a function of te concentration. A thermodynamic scheme
      covering all single reactions relevant for TetR induction was used to interpret
      the data. The equilibrium association constants of the TetR-[Mg-tc]+ and TetR-[Mg
      tc]2+ complexes to tetO were determined at different NaCl and TetR
      concentrations. Variation of total TetR concentration from 0.2 to 1.1 x 10(-7) M
      yielded identical results. A strong salt dependency of TetR-tetO binding was
      verified between 2.5 and 100 mM NaCl, whereas [Mg-tc]+ binding to TetR is
      independent of the ionic strength. The TetR-tetO binding constant drops 10(2)- to
      10(3)-fold upon binding of the first and further 10(4)- to 10(7)-fold by binding
      of the second [Mg-tc]+. This apparent cooperativity of tc-mediated induction
      indicates that each [Mg-tc]+ interacts with both TetR monomers.

PMID- 8747473
TI  - Fluorescence recovery assay: a continuous assay for processive DNA polymerases
      applied specifically to DNA polymerase III holoenzyme.
AB  - A continuous assay was developed for processive DNA polymerases. The specific
      enzyme used to develop the assay was the most processive polymerase known,
      Escherichia coli DNA polymerase III holoenzyme. The assay was based upon the
      recovery of the intrinsic fluorescence of single-stranded DNA binding protein
      (SSB) as it was displaced from the DNA template during DNA synthesis. The
      intrinsic fluorescence of SSB was quenched by as much as 80% when it bound to
      single-stranded DNA. As the DNA was replicated, SSB was displaced and recovered
      its fluorescence. The amount of fluorescence recovered was directly proportional
      to the amount of DNA synthesized and was used to quantitate the rate of DNA
      synthesis. However, since 50 to 60 nucleotides must be replicated for every SSB
      tetramer released, the assay is expected to work best for processive DNA
      polymerases. The only requirement for using this assay with other DNA polymerases
      is that they be able to synthesize DNA on a template coated with SSB. The
      replication SSBs do not pose an obstacle to the assay because they all appear to
      have intrinsic fluorescence that is sensitive to their ssDNA-bound state.

PMID- 8747475
TI  - Chemienzymatic synthesis of uridine nucleotides labeled with [15N] and [13C].
AB  - UTP, labeled with 15N and 13C (at all carbon atoms of the ribose moiety), was
      obtained enzymatically from [15N]uracil and [13C6]glucose. Eleven enzymes and
      suitable substrates reconstituted a metabolic pathway in which glucose was first
      transformed to 5-phosphoribosyl-1-pyrophosphate. The latter compound plus uracil
      yielded UMP in a second step by the reaction catalyzed by uracil
      phosphoribosyltransferase. UMP was subsequently phosphorylated to the
      corresponding di- and triphosphate. ATP, required for five phosphorylation
      reactions, was regenerated from creatine phosphate, whereas NADP+ necessary for
      the oxidation of glucose 6-phosphate and 6-phosphogluconate was recycled by
      glutamate dehydrogenase and excess of ammonia and alpha-oxoglutarate. Despite the
      number and complexity of the enzymatic steps, the synthesis of [15N, 13C]UTP is
      straightforward with an overall yield exceeding 60%. This method, extended and
      diversified to the synthesis of all natural ribonucleotides, is a more economical
      alternative for obtaining nucleic acids for structural analysis by heteronuclear
      NMR spectroscopy.

PMID- 8747476
TI  - Assay of ribozyme-substrate cleavage by anion-exchange high-performance liquid
      chromatography.
AB  - An HPLC procedure has been developed that can be used to monitor the rate of
      phosphodiester cleavage of an oligoribonucleotide substrate by an RNA ribozyme
      with catalytic activity. The method operates at high substrate concentrations
      (far beyond K(m)), thus allowing the reactions to approach Vmax of the reaction.
      This method is an efficient alternative to radioisotope labeling methods.

PMID- 8747477
TI  - Monitoring of ubiquinol-10, ubiquinone-10, carotenoids, and tocopherols in
      neonatal plasma microsamples using high-performance liquid chromatography with
      coulometric electrochemical detection.
AB  - A method for measuring the lipophilic antioxidants alpha-tocopherol, gamma
      tocopherol, ubiquinol-10, ubiquinone-10, beta-cryptoxanthin, and beta-carotene in
      5 or 10 microliters neonatal plasma is presented. First lipid extraction together
      with the internal standards gamma-tocotrienol, ubiquinone-7, ubiquinol-9,
      ubiquinone-9, and ethyl beta-apo-8'-carotenoate was carried out. Then the
      components were separated on a RPC2/C18 column. Coulometric electrochemical
      detection was performed using the reduction-oxidation mode (-0.60 V; -0.15 V;
      +0.60 V). Detection limits for all components were between 21 and 60 fmol,
      corresponding to 0.004 and 0.012 mumol/liter plasma; the within-day precision
      (coefficient of variation) was between 3 and 14% for all measured substances.
      Reference values are given for healthy newborn children from the second to the
      sixth day of life. Using the presented HPLC technique it is possible to monitor
      the concentrations of lipophilic antioxidants in plasma of sick immature newborn
      children in order to study effects of oxidative stress.

PMID- 8747478
TI  - Biotinylated lipopolysaccharide binds to endotoxin receptor in endothelial and
      monocytic cells.
AB  - Endotoxin or lipopolysaccharide (LPS), a major cell surface component of gram
      negative bacteria, which could bind to different cell types when released into
      the bloodstream, plays a central role in the pathogenesis of septic shock
      syndromes. We have established a biotinylation procedure for labeling purified
      LPS molecules from Salmonella minnesota R595 and Escherichia coli J5 bacteria.
      The biotin group was conjugated to the bacterial LPS either by chemical oxidation
      of the LPS carbohydrate moiety (inner core region), followed by reduction with
      biotin-LC-hydrazide (biotinamido hexanoyl hydrazide), or by photoactivatable
      cross-linking with biotin-LC-ASA [1-(4-azidosalicylamido-)-6(biotinamido)
      hexane], which was randomly attached to the carbohydrate and fatty acid (lipid A)
      groups of the LPS. Both labeled products retained biological activity (or
      endotoxicity) as evidenced by coagulation of the Limulus amoebocyte lysate. To
      determine its ability to bind avidin/streptavidin which in turn could be
      conjugated with enzymatic and fluorescent probes, the biotinylated LPS was used
      in enzyme immunoassay, Western blot, and flow cytometry. These assays were also
      used to analyze the binding of LPS ligand to its counterreceptor(s) on whole cell
      surface, membrane fragments, and in detergent lysates from human endothelial and
      monocytic cells. The described biotinylated LPS probes can be applied in a wide
      variety of techniques in receptor biochemistry, immunohistochemistry, and
      molecular cell biology.

PMID- 8747479
TI  - Direct solution hybridization of guanidine thiocyanate-solubilized cells for
      quantitation of mRNAs in hepatocytes.
AB  - The sensitivity of direct solution hybridization of hepatocytes solubilized in
      guanidium thiocyanate (GuSCN) for detecting alpha 1-acid glycoprotein and albumin
      mRNAs was studied. The sensitivity of detection was inversely correlated with the
      DNA concentration. Raising the hybridization temperature from 20 to 37 or 50
      degrees C (with formamide) increased the hybridization efficiency three- to
      fourfold in cell lysates with a high DNA concentration (1 microgram/microliter),
      whereas the hybridization efficiency was already maximal at 20 degrees C in
      diluted samples. It was most important to normalize all hybridization reactions
      with an internal standard, such as sense mRNA, because of the great variation in
      hybridization efficiency from one cell preparation to another depending on the
      DNA concentration. Direct hybridization of GuSCN cell lysates labeled in vivo
      with [6-14C]orotic acid was more efficient than hybridizing equivalent amounts of
      purified [6-14C]-labeled RNA, perhaps because of greater mRNA integrity and/or
      better recoveries of mRNA in GuSCN cell lysates. Therefore, direct solution
      hybridization of GuSCN-solubilized hepatocytes, which avoids the problem of RNA
      purification, appears to be a rapid, sensitive, and reliable method for
      quantifying mRNA in hepatocytes.

PMID- 8747480
TI  - Quantitative analysis of pulmonary surfactant proteins B and C.
AB  - A procedure for the quantification of surfactant protein B (SP-B) and surfactant
      protein C (SP-C) in surfactant preparations is described. After butanol
      extraction of surfactant, the resulting extract is separated by Sephadex LH-60
      HPLC, using an elution fluid which consists of 30% dichloromethane, 65% methanol,
      and 5% 100 mM HCL. SP-B and SP-C are detected by absorbance at 228 nm and
      quantified using standard stock solutions. Run length is approximately 70 min.
      Detection limits are 1 microgram SP-B and 4 micrograms SP-C.

PMID- 8747481
TI  - Use of a polyethylene glycol-peptide conjugate in a competition gel shift assay
      for screening potential antagonists of HIV-1 Tat protein binding to TAR RNA.
AB  - Interference of binding of Tat protein to TAR RNA in HIV-1-infected cells may be
      a useful therapeutic strategy for AIDS. An electrophoretic assay to screen
      potential low-molecular-weight (< 2 kDa) Tat antagonists has been established. A
      radiolabeled TAR RNA fragment (delta TAR) is retarded in mobility when bound by a
      Tat peptide-polyethylene glycol conjugate (Tat-PEG), which is used in place of
      the Tat protein. The assay determines the ability of a potential antagonist to
      compete with Tat-PEG for binding to delta TAR, as measured by interference with
      the gel shift of delta TAR. To discriminate between specific and nonspecific
      interactions, the assay is done in the absence or the presence of a 250-fold
      molar excess of tRNA.

PMID- 8747482
TI  - Microplate superoxide dismutase assay employing a nonenzymatic superoxide
      generator.
AB  - The antioxidant enzyme superoxide dismutase (EC 1.15.1.1) (SOD) catalyzes the
      conversion of superoxide anion radical (O2.-) to hydrogen peroxide and molecular
      oxygen. SOD helps prevent tissue damage by O2.- and its metabolites, and
      augmentation of tissue SOD is a useful therapeutic strategy in certain diseases
      having an oxidative-injury component. Routine application of direct SOD assays is
      not technically facile, since the short half-life of the O2.- substrate and its
      free radical nature necessitate specialized analytical equipment to detect and
      measure O2.- chemically. Consequently, indirect SOD assays which monitor some
      change in an indicator substance reacting with O2.- are routinely used,
      particularly for biological samples. Limitations of indirect test systems
      utilizing heme-based indicators for the presence of O2.- and/or enzymatic O2.-
      generators led us to develop a SOD microassay based on spectrophotometric
      assessment of O2.- mediated nitro blue tetrazolium reduction by an aerobic
      mixture of NADH and phenazine methosulfate, which produces superoxide chemically
      at nonacidic pH (Rao, Free Radical Biol. Med. 7, 513-519, 1989). The proposed SOD
      assay system is formatted for use in an automated 96-well microplate reader and
      has the virtues of a nonheme indicator, a nonenzymatic O2.- source, physiological
      pH, and economy of time and materials. The assay has been applied to measure
      purified and tissue SOD (Cu,Zn- and Mn-types) activity as well as O2.- turnover
      by small-molecule "SOD mimetics."

PMID- 8747483
TI  - Thermal stability of oligodeoxynucleotide duplexes bound to nitrocellulose
      filters.

PMID- 8747484
TI  - Detection of poly(ADP-ribose) polymerase and its apoptosis-specific fragment by a
      nonisotopic activity-western blot technique.

PMID- 8747485
TI  - Total in vitro synthesis of plasmid DNA facilitates site-directed mutagenesis.

PMID- 8747486
TI  - A primer extension method for quantitation of in vitro synthesized mRNA
      transcripts directed by promoter elements containing multiple transcription
      initiation sites.

PMID- 8747487
TI  - Aminooxy acetic acid: a selective inhibitor of alanine:glyoxylate
      aminotransferase and its use in the diagnosis of primary hyperoxaluria type I.
AB  - The diagnosis of primary hyperoxaluria type I is usually based on the
      determination of the activity of the hepatic peroxisomal enzyme
      alanine:glyoxylate aminotransferase (AGT). The activity observed, however, is due
      to the action of at least one more enzyme, i.e. glutamate:glyoxylate
      aminotransferase (GGT). Correction for the AGT activity displayed by GGT is
      usually made by use of a correction factor which correlates the activity of GGT
      with the amount of 'AGT' activity exhibited by GGT. This method, however, has a
      number of drawbacks: it corrects for only one other enzyme and it requires a
      second, rather insensitive and laborious enzyme assay to be performed which
      cannot be adapted to a centrifugal analyser. We therefore developed a simple and
      direct method for measurement of 'true' AGT activity which uses 100 mumol/l
      aminooxy acetic acid. Under these conditions AGT is completely inhibited and the
      contribution of GGT (and possibly other transaminases) to the L-alanine mediated
      transamination of glyoxylate can be measured directly. The 'true' AGT activities
      measured by this method correlated well with those measured in samples depleted
      of AGT by immunoprecipitation. Finally, this method proved to be fully compatible
      with the automated assay of AGT in a centrifugal analyser.

PMID- 8747488
TI  - Acetylcholinesterase of human intestinal tissue affected by Hirschsprung's
      disease: effect of magnesium chloride on isoforms.
AB  - Acetylcholinesterase (AChE) molecular isoforms from anglionic and adjacent
      unaffected (control) colonic tissue in patients with Hirschsprung's disease (HD)
      were analysed by density gradient centrifugation in order to determine the major
      AChE isoforms and the effect of a reported MgCl2 inactivation assay method upon
      them, with a view to improving the AChE assay used in the diagnosis of
      Hirschsprung's disease. The total AChE level was greater in the HD-affected
      colonic tissue than the control tissue (HD: 9.0 vs. control: 7.3 units/g tissue)
      and this was due to a consistently greater elevation of the globular tetrameric
      form, G4 (HD: 48.8% vs. control: 35.5% of total AChE). The inactivation of whole
      tissue homogenates by brief exposure to 4 mol/l MgCl2 followed the same pattern
      (HD: 48.4% vs. control: 28.7% inactivation). The detergent-extractable G4 is
      inhibited to a greater extent than the low salt-soluble G4 by exposure to 4 mol/l
      MgCl2 (83.8% vs. 51.1%). These results imply that the elevated AChE levels in HD
      are mainly due to increases of the hydrophobic globular tetrameric form of AChE
      of the same type that is found in differentiating nervous tissue before synapse
      formation. The monomeric globular isoform G1 is not inhibited but the asymmetric
      A4, A8 and A12 isoforms are completely inhibited by exposure to 4 mol/l MgCl2.
      All isoforms of Torpedo (electric ray) electroplax and human erythrocyte AChE,
      mainly amphiphilic G2, are almost completely inhibited. The inhibition by 4 mol/l
      MgCl2 of the main G4 isoform in HD-affected intestine accentuates the difference
      between aganglionic and unaffected intestine in fractionated samples, but does
      not provide a sufficiently specific G4 isoform assay. The use of 2-4 mol/l MgCl2
      in histochemical AChE staining reduces the activity slightly but does not
      differentiate the tetrameric AChE isoform that is increased in Hirschsprung's
      disease but does reduce contaminating erythrocyte AChE levels that can obscure
      the result in blood-stained biopsies. A specific immunochemical stain for
      hydrophobic AChE tetramers or the associated 20 kDa membrane associated subunit
      is therefore needed to provide specificity.

PMID- 8747489
TI  - Measurement of mevalonic acid in human urine by bench top gas chromatography-mass
      spectrometry.
AB  - Urinary excretion of mevalonate was reported to be correlated with endogenous
      cholesterol biosynthesis. A method is described whereby mevalonate (MVA)
      concentration in urine is determined by bench top gas chromatography-mass
      spectrometry after extraction as mevalonalactone (MVL) and conversion to
      mevalonolactone mono-TMS derivative. Within- and between-assay coefficients of
      variation were 4.02% and 8%, respectively. The mean concentration of MVA in 24-h
      urine collections from ten normolipidemic urinary subjects was 203 +/- 49.6 ng/ml
      (range: 44-576 ng/ml). Administration of 40 mg of Pravastatin (an HMG-CoA
      reductase inhibitor) significantly decreased (approximately 50%) the night
      concentration of MVA in five healthy volunteers. This assay could be useful for
      investigation of endogenous cholesterol synthesis rate in various dyslipidemias
      and in response to drug treatment.

PMID- 8747490
TI  - Enhanced susceptibility of low-density lipoproteins to oxidation in coronary
      bypass patients with progression of atheroscerosis.
AB  - Oxidation of low-density lipoprotein (LDL) may play a causal role in
      atherosclerosis. In this study we analyzed whether the severity of progression of
      coronary atherosclerosis is related to the susceptibility of LDL to oxidative
      modification. On the basis of repeated coronary angiography, 28 coronary bypass
      patients were divided into two groups: group A, 12 patients with, and group B, 16
      patients without progression of coronary atherosclerosis. The lag time,
      reflecting the resistance of LDL to oxidative modification, was significantly
      smaller in group A as compared with group B (81 +/- 10 and 93 +/- 15 min,
      respectively). Besides differences in cholesterol and apolipoprotein B
      concentrations, the difference in susceptibility of LDL to oxidation
      significantly contributes to the differences between the progression and the non
      progression group (P = 0.02). In the combined groups of patients, the lag phase
      of LDL for oxidation was positively correlated with LDL cholesterol ester to
      protein ratio (r = 0.53, P = 0.01). It is concluded that LDL samples obtained
      from coronary bypass patients differ with respect to their oxidizability
      depending on progression of atherosclerosis following coronary bypass surgery.

PMID- 8747491
TI  - Purine and carnitine metabolism in muscle of patients with Duchenne muscular
      dystrophy.
AB  - We determined levels of purines, purine metabolites, related enzymes and
      carnitine in muscle of 8 untreated Duchenne muscular dystrophy (DMD) patients, 12
      allopurinol-treated DMD patients and 12 age-matched controls. Muscle of DMD
      patients was found to be deficient in ATP, ADP, adenylsuccinate, hypoxanthine,
      guanine and adenylsuccinate synthetase. In allopurinol-treated DMD patients, mean
      total adenylate level was only three times less than in controls (versus 14 times
      less in untreated DMD patients). Mean inosine monophosphate (IMP), adenine,
      adenosine, inosine, xanthine, guanine, guanosine and uric acid levels were higher
      in allopurinol-treated patients than in controls, while mean adenylsuccinate
      levels were higher than in untreated patients. Allopurinol also restored
      acylcarnitine levels to normal and significantly increased free carnitine levels.
      These findings strongly support the hypothesis that Duchenne muscular dystrophy
      involves alterations leading to blockage of the IMP-->purine pathway and that
      allopurinol treatment favours restoration of purine levels by this route.
      Furthermore, our results suggest that the observed deficiencies in cell
      components unrelated to purine metabolism are long-term secondary effects.

PMID- 8747492
TI  - Determination of serum total lipid and free N-acetylneuraminic acid in
      genitourinary malignancies by fluorimetric high performance liquid
      chromatography. Relevance of free N-acetylneuraminic acid as tumour marker.
AB  - The reliability of total sialic acid (TSA), lipid sialic acid (LSA) and free
      sialic acid (FSA) as markers in genitourinary malignancies was evaluated in 20
      normal subjects, 21 patients with prostatic cancer, 22 patients with urinary
      bladder cancer and 14 patients with renal cell carcinoma. We introduce the new
      concept of 'corrected' lipid sialic acid (CLSA), which expresses the actual
      concentration of sialic acid bound to glycolipds by subtracting the concentration
      of FSA determined by a novel ultrafiltration method. TSA did not show significant
      differences with respect to normal controls, except for renal cell carcinoma,
      whose mean value (879 +/- 145 micrograms/ml) showed a P value < 0.001. Instead,
      CLSA showed only significant differences (P = 0.001), with respect to normal
      controls in stage I and in all grades of renal cell carcinoma. While all data
      indicated significant increases (P = 0.001) in the FSA values, (means +/- S.D.)
      of 0.621 +/- 0.272 micrograms/ml were found in patients with prostatic cancer,
      0.796 +/- 0.443 micrograms/ml in patients with urinary bladder cancer and 0.667
      +/- 0.146 micrograms/ml in patients with renal cell carcinoma. Separate TSA and
      CLSA measurements appeared to be of limited value in the detection of
      genitourinary malignancies. However, results show that FSA was the most sensitive
      of the three markers tested for detecting malignancies.

PMID- 8747493
TI  - Characterization of mitochondrial DNA in primary cardiomyopathies.
AB  - With the aim of studying the involvement of the mitochondrial genome in the
      impairment of heart function, mitochondrial DNA was analyzed by modified primer
      shift-polymerase chain reaction in a panel of young patients affected by primary
      cardiomyopathies. Mitochondrial DNA molecules harboring the 7436 bp deletion were
      specifically found in cardiomyopathic patients as compared with a panel of
      control subjects. The 4977 bp deletion was commonly detected among the subjects
      analyzed whereas none of the specific tRNA gene point mutations generally
      associated with the cardiomyopathic trait were detected. The presence of the 7436
      bp deletion as a consequence of a premature aging of the heart muscle, secondary
      to heart dysfunction, is discussed.

PMID- 8747494
TI  - Evaluation of antibody- and antigen-coated enzymeimmunoassays for measuring
      oestrone-3-glucuronide concentrations in urine.
AB  - A monoclonal antibody to oestrone-3-glucuronide (OG) was generated and
      incorporated into antigen- and antibody-coated competitive enzymeimmunoassays
      (EIAs) using OG-, 6-ketoestrone-6-O-carboxymethyl-oxime (OCMO) and oestrone-3
      hemisuccinate (OHS) as the steroid coating antigens or 'tracers' in each format
      respectively. In the coated-antigen format, standard curves with the lowest mean
      values (pg/well) for sensitivity (1.1 +/- 0.1), mid-point (ED50; 8.2 +/- 0.7) and
      high-point (ED20; 31 +/- 2) were obtained using OCMO coupled to bovine serum
      albumin (BSA) as the coating antigen, and horseradish peroxidase (HRP) as the
      enzyme label coupled directly to the monoclonal antibody. Standard curves
      generated using enzyme-labelled OG, OCMO and OHS as 'tracers' in the antibody
      coated EIA format were all similar, but had higher mean sensitivity, ED50 and
      ED20 values than those obtained in the optimal coated-antigen format. In both EIA
      formats alkaline phosphatase (AP) was found to be inferior to HRP as an enzyme
      label. Measurement of OG concentrations in early morning urine samples from women
      with natural, regular menstrual cycles, using the antigen-coated EIA,
      demonstrated the characteristic elevation in OG concentrations associated with
      the onset of the urinary LH surge. This technically straightforward and robust
      antigen-coated EIA may be of interest to laboratories with a requirement to
      measure OG concentrations in urine, or other biological samples.

PMID- 8747495
TI  - Does plasma neuropeptide-Y immunoreactivity in patients with pheochromocytoma
      depend on hormonal activity of the tumor?

PMID- 8747496
TI  - Parent and sibling influences on adolescent alcohol use and misuse: evidence from
      a U.S. adoption cohort.
AB  - OBJECTIVE: Although adolescent alcohol use has been consistently associated with
      parental drinking behavior, sibling drinking behavior and family functioning, the
      extent to which these associations owe to genetic or shared environmental
      influences has not been previously investigated. Using an adoption study design,
      we sought to determine whether the familial correlates of adolescent alcohol
      involvement were due to common genetic or common environmental effects. METHOD:
      The sample consisted of 653 adopted families ascertained through adoption
      agencies in four U.S. states. Each family consisted of a target adopted
      adolescent, an adoptive mother and an adoptive father. In addition, 68 birth
      adolescents (i.e., biological offspring of the adoptive parents) and 187 second
      adopted adolescents from these families participated in the study. All
      participants completed a mail survey that included assessment of drinking
      behavior and family functioning. RESULTS: The relationship between parental
      problem drinking and adolescent alcohol involvement was moderate and significant
      among birth offspring (corrected multiple correlation, Rc = .30), but small and
      non-significant among adoptive offspring (Rc = .00). The relationship between
      adolescent alcohol involvement and family functioning was substantial for birth
      offspring (Rc = .39), but only modest for adoptive offspring (Rc = .16). The
      nonbiological sibling correlation for involvement with alcohol was significant (r
      = .24) and moderated by sibling pair demographic similarity, such that same-sex,
      similar-age siblings were substantially more similar (r = .45) than opposite-sex,
      dissimilar-aged siblings (r = .01). CONCLUSIONS: These findings suggest that
      adolescent alcohol use is affected minimally by the environmental consequences of
      parent problem drinking and family functioning, but substantially by sibling
      environmental effects.

PMID- 8747497
TI  - Familial resemblances in alcohol use: genetic or cultural transmission?
AB  - OBJECTIVE: Resemblances between parents and children for alcohol use can be due
      both to cultural transmission and genetic inheritance. We examined the genetic
      and environmental determinants of the familial resemblances in alcohol use.
      METHOD: With a parent-twin design a distinction was made between the contribution
      of genetic effects, the environmental influences shared by siblings and the
      effects of cultural transmission from parents to offspring. By questionnaire data
      on whether subjects had ever used alcohol were obtained from 403 Dutch families
      with a twin aged 15-16 years old and from 805 families with a twin aged 17 years
      and older. RESULTS: For 15-16 year olds, the resemblance between parents and
      offspring could be explained either by genetic inheritance or cultural
      transmission. Shared environment explained between 58% and 88% of the individual
      differences in adolescent alcohol use. For twins aged 17 years and older, 43% of
      the individual differences in alcohol use could be attributed to genetic factors
      and 37% to shared environment. There was no evidence for cultural transmission in
      this age group. CONCLUSIONS: For adolescents aged 17 years and older parental
      alcohol use did not create an environment that stimulated alcohol use in
      children. The resemblance for alcohol use between parents and their children aged
      17 years and older could be explained by their genetic relatedness. For 15-16
      year old adolescents, shared environmental influences were more important than
      for older adolescents. Only 10% of this shared environmental variance might be
      influenced by parental alcohol use due to cultural transmission.

PMID- 8747498
TI  - The impact of coping styles and family communication on the social skills of
      children of alcoholics.
AB  - OBJECTIVE: This study examined the relationship between parents alcoholism and
      their young adult children's social skills. Although parental alcoholism was
      hypothesized to be negatively related to children's social skills, this
      relationship was hypothesized to be moderated by family communication styles and
      young adults' coping styles. METHOD: Prior to the actual study, potential
      subjects were screened on a measure of parental alcoholism. To compensate for the
      positively skewed distribution of this variable, a greater percentage of those in
      the upper extreme of the scale were invited to participate in the study. For the
      study, 143 students (77 female) completed self-report measures of parental
      alcoholism, social skills, family communication and coping styles. Subjects also
      had a sibling complete measures of parental alcoholism and family communication.
      RESULTS: Results indicated no significant differences in adult children's social
      skills as a function of parental alcoholism. Furthermore, family communication
      and young adults' coping styles did not appear to moderate this relationship.
      CONCLUSIONS: This is one of a growing number of studies that show that children
      may exhibit undisturbed psychosocial functioning despite having an alcoholic
      parent.

PMID- 8747499
TI  - Do codependent traits involve more than basic dimensions of personality and
      psychopathology?
AB  - OBJECTIVE: Despite widespread use of the term codependency, empirical evidence
      regarding its construct validity is generally lacking. This study analyzed the
      construct validity of codependency as measured by Potter-Efron and Potter-Efron's
      Codependency Assessment Questionnaire (CAQ). It attempted to determine the CAQ's
      factor structure and whether there are any unique relations between symptoms of
      codependency and parental alcoholism after controlling for basic dimensions of
      personality and psychopathology. METHOD: Participants were 467 (246 male, 221
      female) young adult children of alcoholics and controls who contributed complete
      questionnaire data at the fourth wave of a longitudinal study of factors related
      to alcohol use and abuse. RESULTS: The CAQ showed reliability and basically a one
      dimensional structure, and CAQ scores were significantly related to family
      history. Although much of this relation between family history and codependency
      was accounted for by neuroticism and symptoms of general psychopathology, a
      small, but significant, association between family history and codependency
      remained even after statistically controlling for personality and
      psychopathology. CONCLUSIONS: We conclude that, although there may be unique
      aspects of the purported codependency syndrome that are related to a family
      history of alcoholism, most of the relation between codependency and family
      history appears to be "explained" by general negative affectivity.

PMID- 8747500
TI  - The Adolescent Relapse Coping Questionnaire: psychometric validation.
AB  - OBJECTIVE: The present study was undertaken to assess the factor structure and
      psychometric validity of the Adolescent Relapse Coping Questionnaire (ARCQ). The
      ARCQ is designed to assess alcohol and other drug abusing adolescents coping with
      situations providing temptations for alcohol and other drug use. METHOD: This was
      a prospective longitudinal study of 136 (79 male) alcohol and other drug abusing
      adolescents who were an average of 16.9 years old. Consecutive admissions were
      recruited from two adolescent, inpatient alcohol and drug abuse treatment
      facilities. Subjects completed the ARCQ as part of a 1-year-posttreatment
      interview and were subsequently interviewed 2 years posttreatment. RESULTS:
      Analyses yielded three coping factors which were evaluated for construct and
      criterion validity. Factor 1 contained generic cognitive and behavioral problem
      solving strategies, Factor 2 represented self-critical cognitions and Factor 3
      included abstinence-focused coping strategies. The factors had good internal
      consistency (alpha = .78 to .82) and collectively accounted for 40% of the
      variance in the principle components analysis. The abstinence-oriented coping
      factor was significantly correlated with current alcohol and drug use and
      measures of situation appraisal, and significantly predicted alcohol and drug use
      during the year following assessment. CONCLUSIONS: The findings provide evidence
      for the psychometric validity of the ARCQ, provide convergent validation for the
      utility of the temptation-coping construct and further highlight differences
      between adult and teen addictive relapse.

PMID- 8747501
TI  - Seasonal variation in alcohol use.
AB  - OBJECTIVE: The objective of this article is to describe and quantify seasonality
      in a number of indicators on alcohol use. METHOD: The data analyzed cover a
      period between 1988 and 1994, and are collected by a telephone survey of persons
      living in Glasgow and Edinburgh, Scotland. The analysis is on data from 29,256
      respondents. Cosinor analysis is the analytical instrument applied; a dummy
      variable is incorporated in the analysis to model the December peak in alcohol
      use. RESULTS: Annual seasonality in alcohol use excluding drinking behavior in
      December, is highest in the summer. Seasonality with regard to changes in the
      proportion of respondents who report drinking alcohol in the previous month, or
      in the proportion of less regular heavy drinkers, is, although statistically
      significant, not very pronounced. With regard to drinking five or more drinks on
      11 or more occasions in the past month the level of seasonality is very
      pronounced. The December peak in alcohol use powerfully influences the proportion
      of respondents who report drinking alcohol in the previous month, and the
      proportion of irregular and regular heavy drinkers. CONCLUSIONS: The data support
      previous advice that health promotion and health policy activities in relation to
      alcohol use should take place during the December festive period and, if one aims
      at heavy drinking, the summer.

PMID- 8747503
TI  - Meta-analysis of the literature on Alcoholics Anonymous: sample and study
      characteristics moderate findings.
AB  - OBJECTIVE: Reviews of research on Alcoholics Anonymous (AA) have speculated how
      findings may differ when grouped by client and study characteristics. A meta
      analytic review by Emrick et al. in 1993 provided empirical support for this
      concern but did not explore its implications. This review divided results of AA
      affiliation and outcome research by sample origin and global rating of study
      quality. The review also examined the statistical power of studies on AA. METHOD:
      Meta-analytic procedures were used to summarize the findings of 74 studies that
      examined AA affiliation and outcome. Results were divided by whether samples were
      drawn from outpatient or inpatient settings and a global rating of study quality
      that jointly considered use of subject selection and assignment, reliability of
      measurement and corroboration of self-report. Efficacy of dividing study results
      was examined by changes in magnitude of correlations and unexplained variance.
      RESULTS: AA participation and drinking outcomes were more strongly related in
      outpatient samples, and better designed studies were more likely to report
      positive psychosocial outcomes related to AA attendance. In general, AA studies
      lacked sufficient statistical power to detect relationships of interest.
      CONCLUSIONS: AA experiences and outcomes are heterogeneous, and it makes little
      sense to seek omnibus profiles of AA affiliates or outcomes. Well-designed
      studies with large outpatient samples may afford the best opportunity to detect
      predictors and effects of AA involvement.

PMID- 8747502
TI  - Examining mediators of change in traditional chemical dependency treatment.
AB  - OBJECTIVE: Few studies have examined processes that mediate positive outcomes in
      the treatment of substance use disorders. The present study used a theory-driven
      approach to assess mechanisms hypothesized as curative by the traditional
      chemical dependency treatment approach. Several specific disease model processes
      such as accepting powerlessness over alcohol and two processes common to both the
      disease model and other treatment approaches (commitment to abstinence and
      intention to avoid high-risk situations) were studied. It was hypothesized that
      patients entering treatment would manifest high levels of denial, that there
      would be significant reduction of denial and increased endorsement of disease
      model and common processes as a result of treatment and that processes would
      mediate outcome. METHOD: Patients (N = 79; 54 men) in intensive traditional
      alcohol/drug treatment were assessed at entry into treatment, at the end of
      treatment and 1 month following treatment. Both self-report and clinician ratings
      of processes were assessed. RESULTS: Overall, results provided little support for
      study hypothesis. Subjects showed low levels of denial at treatment entry.
      Specific disease model, but not common processes, increased during treatment.
      Common processes, but not disease model processes, predicted relapse. Patients
      with higher levels of commitment to abstinence and greater intentions to avoid
      high-risk situations were at lower risk for relapse. However, greater commitment
      to Alcoholics Anonymous and belief in a Higher Power predicted reduced severity
      of relapse among those who did relapse. CONCLUSIONS: Findings do not support
      prevailing practitioner views regarding how traditional treatment works and
      suggest that interventions in these treatments may be mismatched to patient
      needs.

PMID- 8747504
TI  - Using panel data to determine the effect of advertising on brand-level distilled
      spirits sales.
AB  - OBJECTIVE: The purpose of the present study is to determine the effect that brand
      level advertising has on brand-level spirits demand. METHODS: Using a panel data
      set consisting of 16 brands and 14 years of data, a fixed effects model of brand
      level spirits demand was estimated. RESULTS: It was found that own-brand
      advertising, income, rival-brand price, a time trend and brand loyalty all have a
      significant effect on brand-level spirits demand. CONCLUSIONS: These results
      indicate that brand-level spirits advertising results only in brand switching and
      does not increase the overall size of the market.

PMID- 8747505
TI  - Behavioral and social consequences related to the consumption of different
      beverage types.
AB  - OBJECTIVE: The purpose of this article is to review the literature on the effects
      of beer, wine and spirits on the behavioral consequences of alcohol consumption.
      METHOD: The methods involve library research and analysis of the various
      published articles relating to experimental and survey studies of different
      effects RESULTS: The major results indicate that (1) after spirits consumption
      blood alcohol concentrations rise more quickly than after beer; (2) for most
      behavioral tasks beer creates less impairment than brandy at the same dose
      levels; (3) brandy also leads to more emotional and aggressive responses; (4)
      those who drink beer or beer and spirits have more alcohol-related problems than
      others; and (5) beer drinkers are more likely than others to drink and drive, to
      be arrested for drinking-driving and to be in alcohol-related accidents.
      CONCLUSIONS: It appears that beer and spirits lead to greater problems than does
      wine consumption. However, there is a need for more studies of women and
      confirmed drinkers of various beverages. There is also a need to study the
      effects of wine consumption on behavioral impairment. Lastly, there is a need to
      determine if there is a beer-drinking culture which supports heavy drinking and
      driving after drinking.

PMID- 8747506
TI  - Effects of blood alcohol concentrations on negative punishment: implications for
      decision making.
AB  - OBJECTIVE: A series of studies examined how various blood ethanol concentrations
      influenced the effectiveness of a negative punishment procedure in a risk
      taking/decision-making task. Based on the animal punishment literature plus the
      impression that ethanol diminishes the effects of punishment and impairs decision
      making, it was predicted that individuals receiving alcohol would increase their
      risk- taking behavior despite the presence of a negative punishment stimulus
      (point loss) given on a variable schedule. METHODS: In Experiment 1, a within
      subjects design with repeated measures was used where 10 male subjects played a
      modified computer-generated choice game under three levels of punishment
      certainty, three levels of punishment severity and four ranges of blood ethanol
      (0.00%, 0.01-0.049%, 0.050-0.099%, 0.10-0.15%) RESULTS: Results indicated
      significant decreases in risk taking as either punishment certainty or severity
      was increased. However, no significant effects were found for ethanol, or
      interactions of ethanol with punishment certainty or punishment severity. Two
      additional studies examining aspects of the experimental procedure produced
      similar results CONCLUSIONS: Overall, the results of these studies do not support
      the hypothesis that high concentrations of blood alcohol are sufficient in and of
      themselves to eliminate the suppression function of negative punishment
      contingencies leading to increased risk-taking behavior. The implications of
      these results for understanding blood alcohol effects are discussed.

PMID- 8747507
TI  - Evaluation of macrocytosis by general practitioners.
AB  - OBJECTIVE: Macrocytosis is considered to be an important sign of disease,
      although it often seems to be ignored. The aim of the present study was to assess
      the quality of the work done by general practitioners using macrocytosis as an
      indicator. METHODS: All consecutive outpatients at Tampere City Health Center who
      had blood counts taken during 8 months in 1990 and were found to have
      macrocytosis (MCV > or = 100 femtoliters) that had not earlier been examined,
      were included in this study. The further examinations undertaken were analyzed.
      RESULTS: Of the 9,527 blood counts, previously unexamined macrocytosis was found
      in 3% (n = 287, 154 men and 133 women). Further examination because of
      macrocytosis was undertaken in 65 (42%) men and in 48 (36%) women. Alcohol abuse
      was the most common disease present in 52 (80%) men and in 22 (46%) women. No
      cause for macrocytosis was found in seven men and in 17 women. No difference
      between the examined and unexamined groups was found concerning medical history,
      medications, symptoms, or blood count values, including hemoglobin and MCV.
      CONCLUSIONS: Evaluation of macrocytosis, when undertaken, was well done by
      general practitioners. However, it was performed too seldom and, thus, several
      diseases, especially alcohol abuse, may have been overlooked.

PMID- 8747508
TI  - Multiple authorship: trends over 50 years in the Journal of Studies on Alcohol.

PMID- 8747509
TI  - Enzyme-linked immunosorbent assay (ELISA) for Aleuria aurantia lectin-reactive
      serum cholinesterase to differentiate liver cirrhosis and chronic hepatitis.
AB  - We have established an enzyme-linked immunosorbent assay (ELISA) for total serum
      cholinesterase (ChE) using 2 new monoclonal antibodies (mAbs) to ChE
      (E.C.3.1.1.8). The ELISA results correlated very well with the results of a serum
      ChE activity assay, which has been widely used for differentiating patients with
      liver diseases, such as hepatocellular carcinoma, liver cirrhosis and chronic
      hepatitis, from normal individuals. We next established an ELISA for Aleuria
      aurantia lectin (AAL)-reactive serum ChE using one of the anti-ChE mAbs and AAL,
      which specifically recognizes L-fucose alpha 1-->2, L-fucose alpha 1-->3, and L
      fucose alpha 1-->6 structures. The ratio of AAL-reactive ChE to total ChE in sera
      determined by the two ELISA procedures was increased in patients with
      hepatocellular carcinoma and liver cirrhosis compared with patients with chronic
      hepatitis and normal individuals. We then applied the ELISA for AAL-reactive ChE
      directly to 10-fold-diluted serum samples, and by using a cut-off value of the
      mean + 2S.D. for normal individuals, we could effectively differentiate liver
      cirrhosis from chronic hepatitis. This single ELISA for AAL-reactive ChE could be
      a useful aid in clinical diagnosis.

PMID- 8747510
TI  - Urinary C4 excretion in systemic lupus erythematosus.
AB  - The fourth component of complement (C4) in urine was measured in 19 patients with
      systemic lupus erythematosus (SLE). Urinary C4 was detectable in all SLE patients
      using an enzyme linked immunosorbent assay. In 11 of 13 patients whose urinary C4
      was serially measured, a decrease of urinary C4 was found in parallel with a
      decrease of disease activity of SLE. In the remaining 2 patients, the amount of
      C4 increased preceding a flare-up of the disease. The measurement of urinary C4
      may be useful in evaluating the disease activity of SLE in individual patients
      and sometimes in predicting the flare-up of the disease. The specific hemolytic
      activity of excreted C4 and Western blotting analysis showed that urinary C4
      consisted mainly of degraded fragments of C4. In two cases, camostat, a serine
      protease inhibitor, rapidly decreased the urinary C4 excretion, suggesting that
      the complement activation occurred in the glomerulus in lupus nephritis.

PMID- 8747512
TI  - A trinucleotide deletion together with a base duplication event at codon 439 in
      the human tyrosinase gene identifies a mutational hotspot.
AB  - Molecular analysis of the human tyrosinase gene in two patients suffering from a
      temperature-sensitive form of albinism has identified a thymine triplet deletion
      at codon 439 which is accompanied by a duplication of the immediately preceding
      cytosine residue. This results in a two base pair frame shift leading to
      premature termination at codon 448, giving a truncated protein. Its relationship
      to other mutations in tyrosinase and the possible cause are discussed. The
      temperature-sensitive phenotype is due to the guanine to adenine mutation at
      codon 422, known to generate a temperature-sensitive enzyme. The CTTT at F439 in
      tyrosinase is also present at F508 in CFTR, the main mutation causing cystic
      fibrosis.

PMID- 8747511
TI  - Non-specific increase of serum carbohydrate antigen 19-9 in patients with liver
      disease associated with increased circulating levels of adhesion molecules.
AB  - Sialyl-Lewisa antigen (SLe(a)), the immune determinant of carbohydrate antigen 19
      9 (CA 19-9), is the ligand of E-selectin. To verify the possibility of an
      association between nonspecific elevation of CA 19-9 and adhesion molecules, sera
      from 12 patients with acute hepatitis, 55 with non-cirrhotic chronic liver
      disease, 33 with cirrhosis and 25 with hepatocellular carcinoma, were tested for
      common liver function tests. Besides, CA 19-9 and soluble forms of E-selectin,
      VCAM-1 and ICAM-1 were measured immunoenzymatically. One-way analysis of variance
      demonstrated that mean CA 19-9 concentration differed among groups (F 15.27, P <
      0.0001) with the highest values found in patients with acute hepatitis. By
      univariate analysis, the strongest correlation of CA 19-9 was with soluble ICAM
      1, which by stepwise multiple regression analysis was the only independent
      predictor of elevated CA 19-9 (multiple R 0.560). The association between ICAM-1
      and CA 19-9 might originate in the biliary cells where they might be
      simultaneously overexpressed during inflammatory processes.

PMID- 8747513
TI  - Direct double antibody sandwich immunoassay of mucin M1 epitopes in human mucus
      secreting pancreatic cell lines.
AB  - A direct sandwich enzyme immunoassay using two monoclonal antibodies was
      developed in order to quantify mucin M1 antigens produced by two pancreatic
      adenocarcinoma cell lines: CAPAN-1 and CFPAC-1. As a solid phase, the wells of a
      microtiter plate were coated with a first monoclonal antibody, 1-13 M1 and the
      biotinylated monoclonal conjugate 9-13 M1 was used as the second antibody. The
      assay was optimized with streptavidin-peroxidase. The detection limit of the
      assay is 1.6 ng/ml. This ELISA is highly specific, sensitive, reproducible and
      quickly performed. It will permit the comparison of mucin exocytosis by the two
      cell lines in response to secretagogue agents and may help in the study of the
      pathogenesis of mucus hypersecretion such as cystic fibrosis.

PMID- 8747514
TI  - Type 1 collagen synthesis by skin fibroblasts from 17 patients with osteogenesis
      imperfecta type III.
AB  - The aim of this study was to look for osteogenesis imperfecta (O.I.) specific
      features in collagen synthesised by skin fibroblast cultures obtained from
      patients with severe progressive deforming O.I. type III. Results from 17 O.I.
      type III cultures were contrasted with results from 6 relatives, 3 unrelated
      controls, 6 O.I. type II, 7 O.I. type IV and 7 O.I. type I cultures.
      Biosynthesised radiolabelled collagen types I and III were extracted and
      separated by gel electrophoresis as intact alpha chains or as cyanogen bromide
      digested peptides. Various abnormalities of type I collagen synthesis were
      detected in cultures from 13/17 O.I. type III patients. In conclusion,
      synthesised collagen abnormalities were detected in cells from most O.I. type III
      patients studied and were O.I.-specific, not O.I. type III-specific at the
      individual level. However, the frequency of detection of these features was
      partially specific to the O.I. type III phenotype.

PMID- 8747516
TI  - Plasma carnitine concentrations in pregnancy, cord blood, and neonates and
      children.

PMID- 8747515
TI  - Effects of membrane incorporation of short-chain phospholipids on sodium pump
      function in human erthrocytes.
AB  - Erythrocyte membrane incorporation of exogenous short-chain diacyl
      phosphatidylcholines (PC) has been quantified by gas chromatography of fatty acid
      methyl esters of extracted membrane lipids after incubation of cells with
      sonicated aqueous suspensions of PC. The PCs studied included didecanoyl PC (C10
      PC), dilauroyl PC (C12-PC), dimyristoyl PC (C14-PC) and dipalmitoyl PC (C16-PC).
      PC incorporation of 10-15 mol% was achieved by incubation at 37 degrees C for 0.5
      24 h. Control cells incubated in saline alone showed a progressive reduction in
      endogenous polyunsaturated acyl chain content. Incubation with C10-PC and C16-PC
      was associated with reductions in membrane cholesterol. Experiments were
      performed with mixtures of PC and cholesterol in order to minimise this effect.
      Short-chain PC incorporation was associated with increases in intracellular Na+
      and reduced intracellular K+ concentrations. Sodium pump activity was measured as
      the ouabain-sensitive rate of 86Rb+ influx and was significantly reduced by all
      PCs tested; mean reductions were 13-30%. These results confirm that the sodium
      pump in situ is sensitive to lipid acyl chain composition.

PMID- 8747517
TI  - Intra-individual variation of overnight urinary albumin excretion in clinically
      healthy middle-aged individuals.

PMID- 8747518
TI  - Cell biology of tissue factor, the principal initiator of blood coagulation.

PMID- 8747519
TI  - Quantitative measurement of various 5-HT receptor antagonists on platelet
      activation induced by serotonin.
AB  - The effects of S2-serotonergic receptor antagonists, ketanserin, MCI-9042, and
      one of its major metabolite, M-1, were evaluated on human platelet activation
      induced by serotonin. A newly developed method for detecting particles in
      suspensions was used to assess serotonin-induced platelet aggregation. Serotonin
      added to platelets in plasma induced transient formation of small aggregates but
      not that of large ones. All the three antagonists in a dose-dependent manner
      suppressed serotonin-induced platelet aggregation. The ID50 values for
      ketanserin, MCI-9042, and M-1 are 10 nM, 0.6 microM, and 40 nM, respectively. The
      effects of these antagonists were also evaluated on [Ca+2]i elevation and shape
      change, the measurement of which does not require the presence of plasma
      proteins. These antagonists effectively inhibited [Ca+2]i elevation and shape
      change induced by serotonin. The ID50 value for MCI-9042 was approximately 1/10
      for platelet aggregation. These findings suggest that MCI-9042 tightly binds to
      plasma proteins with resultant reduction in overall potency. The ID50 values
      obtained in this study are essentially equivalent to those reported for S2
      serotonergic receptor binding in rabbit platelets, suggesting that these agents
      are also potent antagonists serotonin-induced activation of human platelets.

PMID- 8747520
TI  - Study on pharmacokinetics of radioactive labelled defibrotide after oral or
      intravenous administration in rats.
AB  - Defibrotide (D) was labelled with 125I or with 32P. The radiolabelled compounds
      ([125I]-Defibrotide ([125I]-D), [32P]-Defibrotide ([32P]-D) retained the same
      profibrinolytic activity, in vitro, as the parent drug, suggesting that the
      labelling procedures had not modified the pharmacological properties of D and
      hence that its chemical structure was not affected significantly. After single
      intravenous or oral administration of [125I]-D or [32P]-D the pharmacokinetic
      parameters for the two labels were generally in good agreement (75%). t 1/2 alpha
      was in the range of minutes while t 1/2 beta was in the range of hours.
      Bioavailability, following single oral administration of [125I]-D or [32P]-D, was
      in the range of 58-70%. These data suggest that D, in spite of its macromolecular
      nature, is absorbed, after oral administration, fairly well.

PMID- 8747521
TI  - Localization of a calcium-dependent epitope to the amino terminal region of the
      Gla domain of human factor IX.
AB  - We have used site-directed mutagenesis to define the epitope of calcium-dependent
      monoclonal antibodies to human factor IX. We demonstrate that the calcium
      specific epitope includes residues 1-11 of factor IX, with apparent contributions
      from other regions of the protein. Antibodies JK.IX-1, -3, and -4 had critical
      portions of their epitopes in the first eleven amino acids of the Gla domain.
      These three antibodies could bind to a chimera containing the factor VII Gla
      domain, in which surface residues 3, 4, 5, 9, 10, and 11 were modified to those
      of factor IX. In contrast, the epitope of JK.IX-2 was unaffected by mutations in
      residues 3-11 of factor IX, but was dependent on the amino terminal tyrosine
      residue. Furthermore, the calcium-dependent monoclonal antibodies, JK.IX-1, -3,
      and -4, whose epitope include residues 3 through 11. inhibit factor IX's binding
      to endothelial cells, for which the binding site on factor IX has been localized
      to this region. Our results, together with previous studies, confirm the
      existence of discrete calcium and metal-dependent epitopes within the Gla domain
      of factor IX and show that the calcium-specific epitope lies near the amino
      terminus region of this domain.

PMID- 8747523
TI  - Prevalence of impaired responsiveness to epinephrine in platelets among Japanese.
AB  - The responsiveness of platelets only to epinephrine was markedly impaired in
      23/140 (16%) healthy Japanese. The impaired responsiveness was not altered by
      changes in time and environment. Circulating level of catecholamines did not
      affect the responsiveness of platelets to epinephrine. A pilot family study
      indicated a possible familial nature of the defect. 3H methyl-yohimbine binding
      studies indicated that this defect was due to the decreased number of alpha 2
      adrenergic receptor. Despite the defect, the potentiating effect of epinephrine
      on platelet aggregation stimulated by a low dose of ADP was normal. This
      abnormality is not apparently associated with any bleeding disorders and the
      clinical implication is unknown at present. It is, however, essential to
      acknowledge the prevalence of such defect in pursuing research on platelets
      stimulated by epinephrine.

PMID- 8747522
TI  - Regulation of plasminogen activator inhibitor activity by plasmin in endothelial
      cells.
AB  - The fibrinolytic activity in endothelial cells was regulated by balance of
      plasminogen activators and plasminogen activator inhibitors. Plasmin can
      specifically inhibit the biosynthesis of tissue-type plasminogen activator (t
      PA), but not plasminogen activator inhibitor, type 1 (PAI-1) in endothelial
      cells. The PAI activity in the conditioned medium of endothelial cells was low
      and remained constant in 24 hours. However, the PAI activity in the conditioned
      medium of the plasmin-pretreated cells increased linearly in 24 hours.
      Pretreatment with protein kinase C inhibitors, H-7 or staurosporine, partially
      suppressed the PAI activity induced by plasmin. Pretreatment of endothelial cells
      with a G-protein inhibitor pertussis toxin resulted in an inhibition of the
      plasmin-induced PAI activity. The phospholipase A2 inhibitor mepacrine
      specifically eliminated the effect of plasmin stimulation on PAI activity.
      Cyclooxygenase and lipoxygenase inhibitors also partially inhibited the plasmin
      stimulated PAI activity in endothelial cells. All these inhibitors did not affect
      the biosynthesis of the PAI-1 antigen in the presence or absence of plasmin. The
      results indicate that plasmin increased the PAI activity of endothelial cells via
      pathways in which protein kinase C, G protein, and phospholipase A2 may be
      involved.

PMID- 8747525
TI  - A mimetic of the RGDF-peptide [arginine-glycine-aspartic acid-phenylalanine]
      blocks aggregation and flow-induced platelet deposition on severely injured
      stenotic arterial wall. Effects on different animal models and in humans.
AB  - 8-Guanidino-octanoyl-aspartic acid-phenylalanine (SC-49992), a mimetic of the
      tetrapeptide arginine-glycine-aspartic acid-phelylalanine, inhibits fibrinogen
      and vitronectin binding to GP IIb/IIIa. SC-49992 effects on impedance and optical
      aggregation were compared in different species (human, porcine and dog), SC-49992
      induced significant inhibition both in whole blood and PRP aggregation, in all
      species; however, porcine platelets had a SC-49992 IC50 = 2.5 mM while human and
      dog platelets had a significant lower IC50 (1 microM and 1.5 microM,
      respectively). Inhibition of flow-mediated platelet deposition on severely
      injured vessels was studied in porcine blood at high and low shear rates for 5
      minutes. Additionally, studies were performed in vessels with 80% stenosis. SC
      49992 reduced platelet deposition both at high and low shear rate in parallel
      streamlined flow and in stenotic conditions. The lower affinity of porcine
      platelets for SC-49992 seems to be due to a species difference at the GPIIb/IIIa
      receptor RGD-sequence level.

PMID- 8747524
TI  - Platelet lysis and functional perturbation by 13-methyl myristate. The major
      fatty acid in Flavobacterium ranacida.
AB  - Flavobacterium ranacida consisted of 75% of 13-methyl myristate in total fatty
      acids. The acid at > 60 microM caused the lysis of gel-filtered platelets (GFP)
      in both time- and concentration-dependent manners. Scanning electron microscopy
      showed that: 1). GFP in 40 microM of the acid changed the morphology to speculate
      discoid shape at 15 sec, and to ellipsoids after 30 sec; and 2), the cells
      gradually swelled to spherical forms as the concentration of the acid increased.
      At nonlytic concentration, the acid inhibited platelet responses to various
      agonists with differential concentrations. The order of inhibitory potency was
      U46619 > low dose collagen > ADP-fibrinogen > phorbol ester > high dose collagen.
      The results demonstrated that 13-methyl myristate exhibited both cell lytic
      activity and perturbation on membrane function.

PMID- 8747526
TI  - Platelet adhesion at high shear rates: the roles of von Willebrand factor/GPIb
      and the beta 1 integrin alpha 2 beta 1.
AB  - We have previously described a monomeric rvWf fragment, Leu504-Lys728 that
      contains one disulfide bond linking Cys509-Cys695. This fragment, VCL, has
      previously been shown to inhibit vWf-ristocetin, asialo-vWf, and botrocetin
      induced vWf binding and aggregation of platelets. VCL inhibited 50% of vWf
      binding to heparin, but it did not inhibit vWf binding to type I collagen. At a
      high shear force (2600-1 sec), VCL inhibited platelet adhesion to the
      subendothelial surface of human umbilical arteries. The maximum inhibition of
      platelet adhesion was 83 +/- 4% at a VCL concentration of 7.6 mumol/L. Various
      monoclonal anti-Very Late Activation antigens (VLA) antibodies were added to the
      VCL and tested for their ability to enhance the inhibition of platelet adhesion
      at high shear forces. Of all of the VLA antibodies tested, only the anti-VLA-2
      antibody (176D7) inhibited platelet aggregation in the absence of VCL and
      enhanced the inhibition of platelet adhesion in the presence of VCL. The VLA-2
      antibody and VCL together inhibited 96 +/- 4% of platelet adhesion at high shear
      forces.

PMID- 8747527
TI  - Regulation of the thrombin receptor response in human endothelial cells.
AB  - At present only little information is available about the regulation of the
      thrombin receptor activity in human endothelial cells. The study presented was
      performed to clarify the problem of thrombin receptor regulation in human
      endothelial cells. Endothelial cells were isolated from the vein or artery of
      human umbilical cords. These cells were stimulated with thrombin or with the
      thrombin receptor activation peptides (TRAP) SFLLRN or SFLLRNPNDKYEPF and
      subsequently the von Willebrand factor (vWf) release was measured as a
      physiologically significant response regarding the thrombin receptor activation.
      Shortly after the first activation by thrombin or SFLLRN, the cells were
      desensitised to a second stimulation. After a recovery phase of 10 min, merely
      35% of the receptor response was obtained by subsequent stimulation. Expanding
      the recovery time to 90 min resulted in a vWf release of nearly 100% of the
      amount measured after the first stimulation. The resensitisation rate was similar
      for thrombin and SFLLRN stimulated cells. Adding RNA synthesis inhibitors or
      protein synthesis inhibitors had no effect on the recovery of the receptor
      response. Therefore, a de novo synthesis of receptor protein must be excluded as
      a means of resensitising endothelial cells to thrombin. It was shown that the
      dephosphorylation of tyrosine kinase inactivated receptors is also not
      responsible for receptor regeneration. These results prove that endothelial cells
      are capable of developing full thrombin receptor activity after a relatively
      short recovery phase of only 60-90 min as compared to the recovery phase of 16-24
      h in megacaryoblastic cell lines. Desensitisation is similar in thrombin and TRAP
      stimulated cells. We assumed a transport mechanism for intracellular stored
      vesicles for receptor resensitisation; a co-localisation with vWf in the Weibel
      Palade bodies is improbable.

PMID- 8747528
TI  - A study of the fibrinolytic response in healthy men and women following a brief
      exposure to venous occlusion.
AB  - In this study, 176 healthy men and women between the ages of 18 and 25 yrs were
      tested for fibrinolytic activity before and after a 5 min period of venous
      occlusion (VO) at 100 mm Hg. Using this protocol, 140 demonstrated an increase in
      fibrin plate lysis following this brief period of venous occlusion and were
      classified as "Responders." There were 36 individuals in the study who showed
      either a decrease or no change in fibrin plate lysis after 5 min of venous
      occlusion and they were classified as "Non-Responders." Responders showed a
      decrease in PAI-1 following VO. However, neither Responders nor Non-Responders
      demonstrated any significant differences in the levels of plasminogen,
      antiplasmin, protein C, free t-PA, or total t-PA following this brief exposure to
      venous occlusion. When comparing women and men in this study, women had
      significantly greater fibrin plate lysis both before and after 5 min of VO. They
      also demonstrated higher pre- and post-VO levels of circulating plasminogen.
      Also, women had less PAI-1 pre- and post-VO than men. When examining Responders
      and Non-Responders according to gender, women who were Responders had
      significantly greater fibrin plate lysis before and after VO than male
      Responders. Also, women Responders demonstrated a significant decrease in PAI-1
      following 5 min of VO when compared to men who were Responders in this study.

PMID- 8747529
TI  - Fibrinogen Claro--another dysfunctional fibrinogen variant with gamma 275
      arginine-->histidine substitution.

PMID- 8747530
TI  - A more discriminating test for APC resistance and a possible screening test to
      include protein C and protein S.

PMID- 8747531
TI  - Qualitative and quantitative detection of human and recombinant thrombin by
      binding to leech and recombinant hirudin immobilized at the solid phase.

PMID- 8747532
TI  - Regulation of cAMP phosphodiesterases by cyclic nucleotides in rat parotid gland.
AB  - Approximately 88% of the total cAMP phosphodiesterase (PDE) activity was detected
      in the supernatant fraction of the rat parotid homogenate. Mono Q ion-exchange
      chromatography revealed five main peaks (PDE I, PDE II, PDE III, PDE IV and
      unknown). A high concentration of cGMP (> 1 microM) was necessary to activate PDE
      II, whereas PDE III was inhibited by cGMP at a concentration that was 1,000 times
      lower (100 pM). PDEs III and IV were activated by treatment with a catalytic
      subunit of cAMP-dependent protein kinase (A kinase), and H-8, a A kinase
      inhibitor, inhibited the activation. Treatment of parotid slices with 1 microM
      isoproterenol stimulated PDE activity by approximately 120%, and 10 microM
      propranolol inhibited the activation.

PMID- 8747533
TI  - A molecular variant of plasminogen activator inhibitor of rat decidual tissue.
AB  - Artificially induced rat decidual tissue expresses plasminogen activator
      inhibitor (PAI). This PAI, isolated and purified employing chromatographic
      techniques, is a low molecular weight protein unlike the known PAIs. The final
      purified preparation resolves into a single band following SDS-PAGE and has an
      approximate molecular weight of 29 kDa. The properties studied include
      specificity for urokinase-type (uPA) and tissue-type (tPA) plasminogen
      activators, binding to conA and heparin, inhibition of thrombin, plasmin and
      trypsin. Decidual PAI is immunogenic in rabbit and a monospecific antiserum
      raised against the decidual inhibitor cross reacts with an extract of human
      placenta.

PMID- 8747534
TI  - A quick procedure for the isolation of dimeric piratoxins-I and II, two myotoxins
      from Bothrops pirajai snake venom. N-terminal sequencing.
AB  - Two myotoxins, MP-I and MP-II, from Bothrops pirajai snake venom, have been
      purified by a quick high performance liquid chromatography (HPLC) procedure.
      Based on the HPLC coelution profile, amino acid composition, N-terminal sequence,
      polyacrylamide gel electrophoresis (PAGE) migration, as well as lack of
      phospholipase-A2 (PLA2) and proteolytic activities, MP-I and MP-II were
      identified as piratoxin-I (PrTX-I) and II (PrTX-II), respectively. This procedure
      affords, aside the reduced operation time, a high yield (35% of the applied
      sample in terms of A280nm) of MP-I, which is the major myotoxin of the venom. The
      N-terminal sequences of MP-I, MP-II, PrTX-I and PrTX-II, up to the 51st, 41st,
      46th and 39th residues, respectively, have been determined, revealing MP-I (and
      hence PrTX-I) as a Lys-49 PLA2-like myotoxin. Both MP-I and MP-II have been
      shown, by SDS-PAGE, to occur in dimeric isoforms.

PMID- 8747535
TI  - The lactate dehydrogenase gene from nematode Caenorhabditis elegans contains only
      two of six introns conserved in the protein-encoding sequence of LDH genes from
      bird and mammals.
AB  - The protein-encoding region of L-lactate dehydrogenase (LDH) gene from nematode,
      Caenorhabditis elegans, was amplified by polymerase-chain-reaction from total
      genomic DNA and its nucleotide sequence determined. A comparison of this genomic
      sequence with the published sequence of nematode LDH cDNA reveals the presence of
      two introns of 57 and 47 nucleotides at codon no. 82 and 279-280, respectively.
      The positions of the two introns present in this invertebrate LDH gene correspond
      to the second and sixth introns of vertebrate LDH genes. The protein-coding
      sequence of human LDH-A (muscle), LDH-B (heart) and LDH-C (testis), mouse LDH-A,
      and duck LDH-B genes has previously been shown to be interrupted by six introns
      at the homologous positions.

PMID- 8747536
TI  - The neurohormone melatonin inhibits cytokine, mitogen and ionizing radiation
      induced NF-kappa B.
AB  - Recently, the neurohormone melatonin was found to be a potent endogenous hydroxyl
      radical scavenger. Since the activation of an important transcriptional
      regulator, nuclear factor-kappa B (NF-kappa B) involves free radicals as second
      messengers, we investigated whether melatonin alters NF-kappa B expression if
      present during treatment of HeLa S3 cells with known activators. The results show
      that upon treatment of HeLa S3 cells with tumor necrosis factor-alpha or phorbol
      12-myristate 13-acetate, or with ionizing radiation, there is a profound
      induction of NF-kappa B binding activity. If present at the time of treatment,
      exogenously added melatonin, at a concentration as low as 10 microM, was found to
      inhibit the activation of NF-kappa B by these agents. This results leads to the
      hypothesis that melatonin can play a role in many physiological functions through
      its modulation of NF-kappa B (and possibly other) transcriptional regulators.

PMID- 8747537
TI  - Mechanism of potentiation of tissue-type plasminogen activator.
AB  - The conversion of plasminogen to plasmin catalyzed by tissue-type plasminogen
      activator is accelerated in the presence of fibrin, leading to an increased
      dissolution of fibrin clots. This rate enhancement is mimicked by a dodecapeptide
      segment of the fibrin molecule containing the sequence A alpha 149-160
      (RLEVDIDIKIRS). At low concentrations of the dodecapeptide, the potentiation
      increases with concentration, but at high concentrations, the stimulation effect
      diminishes, giving rise to a bell-shaped curve. The maximum rate enhancement of
      about 10 fold is achieved at a concentration of 85 micrograms/mL. This
      concentration dependent phenomenon is also observed for two synthetic peptide
      analogues, GLEVDIDIKIRS and RGGGGGGGKIRS, although the acceleration potential is
      less. These results indicate that the N-terminal amino acids are not critical for
      the rate enhancement. The bell-shaped activity-concentration curve suggests that
      the dodecapeptide may bind to both plasminogen and t-PA. This speculation is
      further supported by the modification of the potentiator. When the A alpha 149
      160 dodecapeptide is pretreated with trypsin or phenyl glyoxal, the potentiation
      activity is eliminated. We speculate that the acceleration of the plasminogen-to
      plasmin reaction catalyzed by t-PA is achieved through the action of the
      stimulator to bring the enzyme and its substrate together as a bi-dentate cross
      linker. This effect increases the apparent concentration of the substrate at the
      enzyme active site, and is reflected as a decrease in Michaelis-Menten constant.

PMID- 8747538
TI  - Impaired mitochondrial metabolism and reduced amphibolic Krebs cycle activity in
      diabetic rat hepatocytes.
AB  - Oxidation of [2,3(14)C] and [1,4(14)C] succinate carbons in the mitochondrial
      Krebs cycle (KC) was used as a probe to investigate the effect of insulin and
      diabetes on mitochondrial metabolism in isolated rat hepatocytes. The data
      presented show that mitochondrial oxidation of succinate carbons and their
      incorporation into protein and lipid was markedly lower in diabetic and insulin
      treated diabetic rat hepatocytes. Unlike controls, diabetic rat hepatocytes were
      unresponsive to in vitro insulin addition. Amphibolic channeling of [2,3(14)C]
      succinate carbons into amino acid fraction was reduced in hepatocytes from
      diabetic rats, however, more of these carbons were diverted into the
      gluconeogenesis pathway. These data suggest that the diminished level of anabolic
      activities in the diabetic rat hepatocytes may be due to impairment in the KC
      reactions and a subsequent reduction in amphibolic channeling of metabolic
      intermediates.

PMID- 8747539
TI  - Rev-erb beta 2, a novel isoform of the Rev-erb family of orphan nuclear
      receptors.
AB  - We have isolated a rat complementary DNA clone corresponding to a novel isoform
      of the hormone nuclear receptor superfamily. This clone encodes a 383 amino acid
      residue protein designated as Rev-erb beta 2. This protein is identical until
      residue 382 to the Rev-erb beta 1 protein, which is 195 amino acids longer.
      Several arguments pointed out that the Rev-erb beta 2 cDNA may originate from the
      same gene as Rev-erb beta 1 by alternative splicing and using a different
      polyadenylation site. Our results indicate that Rev-erb beta 2 is a new isoform
      of the Rev-erb family of orphan nuclear receptors.

PMID- 8747540
TI  - Difference in effects of classic and phospholipid hydroperoxide glutathione
      peroxidases on liver lipid peroxide level in selenium-deficient rats.
AB  - When weanling male rats of the Wistar strain were fed a selenium-deficient diet,
      the activity of classic glutathione peroxidase (GPx) in liver cytosol decreased
      rapidly. In contrast, the activity of phospholipid hydroperoxide GPx (PHGPx) in
      the cytosol decreased only slowly. Despite the marked decrease in classic GPx
      activity, the lipid peroxide level in the liver did not change until 6 weeks
      after the start of the feeding, whereas the level was significantly increased by
      9 weeks, by which time PHGPx activity and its protein level had markedly
      diminished. These data indicate that PHGPx is much more crucial than classic GPx
      in preventing the elevation of liver lipid peroxide level in selenium-deficient
      rats.

PMID- 8747541
TI  - Preservation of mitochondrial respiratory function by coenzyme Q10 in aged rat
      skeletal muscle.
AB  - Pharmacological intervention was investigated into the age-associated decline in
      mitochondrial function. Rats aged 7 weeks were divided into two groups; the
      control group (standard diet), and the coenzyme Q10 group (fed with 0.2% coenzyme
      Q10 diet). Mitochondria from skeletal muscle (psoai major) and cardiac muscle
      were prepared from rats aged 7, 35, and 55 weeks, and enzymic activities were
      measured in four complexes of the mitochondrial electron transport chain. Age
      associated declines in activities of complexes I and IV of psoai major were
      significantly mitigated in the coenzyme Q10 group. The activities of complexes I
      and IV of heart mitochondria did not change significantly throughout the
      experiment in either group. Moreover, aging up to 55 weeks had no significant
      effect on activities of complexes II and III in either tissue. It is concluded
      that intake of a coenzyme Q10 rich diet might retard the normally observed age
      associated decline in overall mitochondrial respiratory function in rat skeletal
      muscle.

PMID- 8747542
TI  - Tissue- and species-dependent expression of sheep lung microsomal cytochrome
      P4502B(LgM2).
AB  - Expression of sheep lung microsomal cytochrome P4502B(LgM2) isozyme was
      determined in lung and liver preparations from rabbits, rats, sheep, cows and
      humans. Several tissues of sheep such as lung, liver, adrenal, kidney, ovary,
      intestine, muscle, spleen, pancreas and brain were also examined. Tissue
      homogenates were analyzed by Western-blotting with an antibody raised against
      purified sheep lung P4502B(LgM2) isozyme in rabbits. This isozyme was detected in
      lung samples from every species examined. Homologues of cytochrome P4502B(LgM2)
      were expressed in livers of sheep and rabbits but not in those of humans and
      cows. Although homologous forms of P4502B(LgM2) were not expressed in sheep
      brain, ovary, pancreas, spleen and muscle tissues, they were expressed in sheep
      adrenal, intestine and kidney.

PMID- 8747543
TI  - Use of UV spectroscopy for the study of nucleic acid cleavage by E. coli RNase H
      and restriction endonucleases.
AB  - A one-step spectrophotometric method for monitoring of nucleic acid cleavage by
      ribonuclease H from E. coli and type II restriction endonucleases has been
      proposed. It is based on recording of the increase in the UV absorbance at 260 nm
      during the course of enzymatic reaction. Duplexes stable under the reaction
      conditions were chosen as substrates for the enzymes being studied. In order to
      obtain duplex dissociation following their cleavage by the enzyme appreciate
      temperature conditions were selected. The spectrophotometric method may be
      applied for rapid testing of the nuclease activity in protein preparations as
      well as for precise quantitative analysis of nucleic acid degradation by enzymes.
      This method may be successfully employed in kinetic studies of nucleic acid
      protein interactions.

PMID- 8747544
TI  - The SRY protein, like HMG 1, recognizes (CA)n sequences, an abundant repeat
      sequence in vertebrates.
AB  - The sex-determining region of the Y chromosome gene, sry is expressed in the
      foetal mouse for a brief period, just before testis differentiation, which could
      be consistent with negative autoregulation. SRY is a DNA binding protein which
      can bind to cruciform DNA and to linear DNA with a sequence specificity. We have
      examined if the Sry gene contain DNA binding sites for the SRY protein itself. We
      have found that in an in vitro assay, the SRY protein binds to several sites of
      the Sry gene and especially to a (CA)25 sequence and to a (CAG)30 repeat. These
      binding suggest that the function of SRY and in a general way HMG-box proteins
      may be mediated by an interaction with repeat sequences.

PMID- 8747545
TI  - The loop region around amino acid residue 50, the N-terminal part of the alpha
      helix, and the C-terminus of human retinol-binding protein are not located in or
      close to the transthyretin binding site.
AB  - Although the three-dimensional structures of both human retinol-binding protein
      (RBP) and transthyretin (TTR) are known, the binding sites have not been defined.
      In this study we have epitope-mapped a rabbit antiserum against human RBP using
      synthetic peptides corresponding to all potentially antigenic sites.
      Immunoreactivity was seen with peptides corresponding to amino acid residues 46
      54, 137-146, 143-153, and 172-182 of RBP. Since previous studies have
      demonstrated that these antibodies bind equally well to free RBP and to the RBP
      TTR complex, we conclude that neither the loop region around amino acid residue
      50, the N-terminal part of the alpha-helix, nor the C-terminus of RBP is located
      in or close to the TTR binding site. Our results support the hypothesis that one
      of the entrance loops is involved in the TTR binding.

PMID- 8747546
TI  - Dilution beyond a transition concentration and the enhanced filaments' formation
      of actin in the low ionic strength buffer.
AB  - Actin in the low ionic strength buffer solution G (0.1 mM ATP, 0.1 mM CaCl2, 2 mM
      Tris-Cl (pH 8.0), 5 mM 2-mercaptoethanol and 1 mM NaN3) was diluted to the
      concentration below 10 micrograms/ml at 7 degrees C. Viscometry showed
      associations of actin monomers and increasing the extent of dilution, maximally
      about 75% of actin were precipitated. Actin filaments were observed by electron
      microscope in the diluted solution. Ca2+ plays a role in the filaments'
      formation. It seems that a phase transition like change in the actin states arose
      at this concentration range.

PMID- 8747547
TI  - A rapid single-step purification method for human interferon-gamma from isolated
      Escherichia coli inclusion bodies.
AB  - A fast purification method for recombinant human interferon-gamma, produced in E.
      coli, was elaborated. Human IFN-gamma accumulated in the cytoplasm of E. coli
      cells as inclusion bodies (IB). After lysis, the IB were isolated from the cell
      debris by means of a density gradient ultracentrifugation, and solubilized in 6 M
      guanidine hydrochloride. The subsequent refolding step was optimized for a
      maximal recovery of the biologically active dimer. Refolded IFN-gamma was then
      purified to homogeneity in a single cation exchange chromatographic step,
      yielding 12.5 mg protein per liter E. coli culture. The dimeric nature of the
      refolded protein was visualized by means of interchain cross-linking. In a
      subsequent Western blot the resulting derivative was recognized by a panel of
      five monoclonal antibodies, indicating that those epitopes on the protein surface
      remained unaffected upon cross-linking.

PMID- 8747548
TI  - Promiscuity of heme groups in the cyanobacterial cytochrome-C oxidase.
AB  - The cyanobacteria Nostoc sp. strain Mac, Anabaena 7937, Synechocystis 6803, and
      Anacystis nidulans (Synechococcus 6301) were grown and incubated in the light
      under three different oxygen regimes: Phase-A cells were harvested from
      photoautotrophically growing cultures at a cell density of 2.8-3.2 microliter
      packed cell mass/ml and an oxygen concentration of approx. 350 microM
      (corresponding to > 150% air saturation). Phase-B cells were harvested 24 hrs
      after 20 microM 3-(3,4-dichlorophyl)-1,1-dimethylurea had been added to the
      culture and gassing switched to 1% oxygen (< 10 microM). Phase-C cells originated
      from phase-B cells after 12 hrs of gassing the illuminated, yet non-growing
      cultures with air (21% oxygen or 200-220 microM in the medium). Cytoplasmic
      membranes were isolated and purified from each of the three cell types. Non
      covalently bound hemes were extracted and identified by reversed-phase high
      performance liquid chromatography. Besides ubiquitous heme B only heme A was
      detected in phase-A membranes while phase-B and phase-C membranes contained both
      hemes A and O proportions of which depended on the oxygen status of the cells.
      CO/difference spectra, photo-action spectra of CO-inhibited oxygen uptake, and
      polarographic determination of oxygen-affinities clearly showed that both hemes A
      and O were part of a functional form of cytochrome-c oxidase which, however,
      exhibited a single subunit-I apoprotein as verified by immunoblotting. Also
      electron transport characteristics did not give evidence for a quinol or any
      other alternate oxidase functioning in cyanobacteria.

PMID- 8747549
TI  - EPR studies on the kinetics of quenching singlet oxygen.
AB  - The specific reaction between singlet oxygen (1O2) and 2,2,6,6-tetra-methyl
      piperidine (TEMP) was utilized to investigate the kinetics of singlet oxygen
      quenching. Rose bengal was used for the generation of singlet oxygen (1O2). The
      deuterium isotope effect (rho) was found to be 22.1. The rate constant (kT) of
      the reaction of TEMP with 1O2 in H2O, D2O and ethanol were found to be 9.0 x
      10(5) M-1s-1, 1.5 x 10(6) M-1s-1 and 7.3 x 10(5) M-1s-1, respectively. The
      intercept of the plot of [TEMPO]-1 at different H2O/D2O ratios was found to be
      constant, indicating the lifetime of 3Sens is independent of solvent deuteration.
      The quenching of 1O2 by azide and the sensitizer itself were confirmed by the
      constant intercept on the kinetic plots. Thus, the quenching rate constants for
      azide anion in ethanol solution (96%) and for ground state rose bengal in 0.05 M
      phosphate buffer (pH 7.4), were found to be 8.36 x 10(8) M-1s-1 and 1.72 x 10(4)
      M-1s-1, respectively. These studies not only verify the specificity of the
      reaction between TEMP and 1O2 but also provide a sensitive and specific assay for
      1O2.

PMID- 8747550
TI  - Purification and characterization of 6xHis-tagged Bm3R1 repressor of Bacillus
      megaterium.
AB  - The bm3R1 gene-encoded repressor controls the expression of cytochrome P450BM-3
      gene as well as its own expression in Bacillus megaterium. We have developed an
      efficient system for overexpression and purification of Bm3R1 protein by nickel
      ion affinity chromatography. Adding six histidine residues at either N-terminus
      or C-terminus of Bm3R1 repressor caused no loss of its operator DNA binding
      ability. We have investigated the interaction between Bm3R1(His)6 and its
      operator DNA by equilibrium and kinetic methods. The results showed that the
      apparent dissociation constant is around 1.8 x 10(-9) M and the half-life of
      Bm3R1(His)6-operator complex is about 50 minutes. We have also found by gel
      filtration chromatography that Bm3R1(His)6 may exist in low oligomeric state(s)
      in solution, which is competent for binding to its operator DNA.

PMID- 8747551
TI  - Estrogen receptor activation factor (E-RAF) of the rat uterus: hormonal control.
AB  - Evidence is presented showing that the synthesis of the estrogen receptor
      activation factor (E-RAF) in the rat uterus is under both estrogenic and
      progestational control. An ELISA method for the measurement of E-RAF is described
      and used to measure the E-RAF titre in the pregnant rat uterus. It is proposed
      that E-RAF synthesis during pregnancy is under the exclusive control of
      progesterone.

PMID- 8747552
TI  - Ribosome-associated ribonucleases from six-day larvae of the insect Ceratitis
      capitata.
AB  - A 34 kDa, poly(U) and poly(C)-specific ribonuclease, is shown to be tightly bound
      on purified polysomes from six-day-old larvae of the insect Ceratitis capitata.
      High salt treatment (400 mM KCl) is necessary to release it completely from the
      polysomes. Removal of the RNase does not disrupt the structure of the ribosomes,
      as shown by centrifugation on sucrose gradients and poly U directed
      polyphenylalanine synthesis.

PMID- 8747553
TI  - Excitation-calcium release uncoupling in aged single human skeletal muscle
      fibers.
AB  - The biological mechanisms underlying decline in muscle power and fatigue with age
      are not completely understood. The contribution of alterations in the excitation
      calcium release coupling in single muscle fibers was explored in this work.
      Single muscle fibers were voltage-clamped using the double Vaseline gap
      technique. The samples were obtained by needle biopsy of the vastus lateralis
      (quadriceps) from 9 young (25-35 years; 25.9 +/- 9.1; 5 female and 4 male) and 11
      old subjects (65-75 years; 70.5 +/- 2.3; 6 f, 5 m). Data were obtained from 36
      and 39 fibers from young and old subjects, respectively. Subjects included in
      this study had similar physical activity. Denervated and slow-twitch muscle
      fibers were excluded from this study. A significant reduction of maximum charge
      movement (Qmax) and DHP-sensitive Ca current were recorded in muscle fibers from
      the 65-75 group. Qmax values were 7.6 +/- 0.9 and 3.2 +/- 0.3 nC/muF for young
      and old muscle fibers, respectively (P < 0.01). No evidences of charge
      inactivation or interconversion (charge 1 to charge 2) were found. The peak Ca
      current was (-)4.7 +/- 0.08 and (-)2.15 +/- 0.11 muA/muF for young and old
      fibers, respectively (P < 0.01). The peak calcium transient studied with mag-fura
      2 (400 microM) was 6.3 +/- 0.4 microM and 4.2 +/- 0.3 microM for young and old
      muscle fibers, respectively. Caffeine (0.5 mM) induced potentiation of the peak
      calcium transient in both groups. The decrease in the voltage-/Ca-dependent Ca
      release ratio in old fibers (0.18 +/- 0.02) compared to young fibers (0.47 +/-
      0.03) (P < 0.01), was recorded in the absence of sarcoplasmic reticulum calcium
      depletion. These data support a significant reduction of the amount of Ca
      available for triggering mechanical responses in aged skeletal muscle and, the
      reduction of Ca release is due to DHPR-ryanodine receptor uncoupling in fast
      twitch fibers. These alterations can account, at least partially for the skeletal
      muscle function impairment associated with aging.

PMID- 8747554
TI  - Determination of the Na permeability of the tight junctions of MDCK cells by
      fluorescence microscopy.
AB  - The kinetics of Na movement across the tight junctions of MDCK cells, grown on
      coverslips and perfused with HEPES or bicarbonate Ringer at 37 degrees C, were
      investigated after filling the lateral intercellular spaces (LIS) of the
      epithelium with SBFO, an Na-sensitive fluorescent dye. Dilution and bi-ionic
      potential measurements showed that MDCK cell tight junctions, although cation
      selective, were poorly permeable to N-methyl-D-glucamine Cl (NMDG) but freely
      permeable to Li. In previous experiments in which Na was replaced by NMDG, a very
      slow decrease in LIS Na concentration (time constant = 4.8 min) resulted. In the
      present study, reduction of perfusate Na from 142 to 14 or 24 mM with Na replaced
      by Li caused LIS Na concentration to decrease with a time constant of 0.43 min.
      The time constant for Na increase of the LIS was 0.28 min, significantly shorter
      than that for Na decrease because of the additional component of transcellular Na
      influx. Ouabain eliminated the transcellular component and equalized the time
      constants for Na influx and efflux. These results were incorporated into a
      mathematical model which enabled calculation of the transcellular and
      paracellular Na fluxes during fluid reabsorption. Regulation of the Na
      permeability of individual tight junctions by protein kinase A (PKA) was
      evaluated by treating the monolayers with the Sp-cAMPS, a cAMP substitute, or Rp
      cAMPS, a specific inhibitor of PKA. Stimulation of PKA strikingly increased tight
      junctional permeability while PKA inhibition diminished junctional Na
      permeability.

PMID- 8747555
TI  - The paracellular channel for water secretion in the upper segment of the
      Malpighian tubule of Rhodnius prolixus.
AB  - Lumen to bath J12/C1 and bath to lumen J21/C2 fluxes per unit concentration of 19
      probes with diameters (dm) ranging from 3.0-30.0 A (water, urea, erythritol,
      mannitol, sucrose, raffinose and 13 dextrans with dm 9.1-30.0 A) were measured
      during volume secretion (Jv) in the upper segment of the Malpighian Tubule of
      Rhodnius by perfusing lumen and bath with 14C or 3H-labeled probes. Jnet =
      (J12/C1-J21/C2) was studied as a function of Jv.Jv was varied by using different
      concentrations of 5-hydroxy tryptamine. Jnet for 3H-water was not different from
      Jv. We found: (i) A strong correlation between Jnet and Jv for 8 probes dm = 3.0
      11.8 A (group a probes), indicating that the convective component of Jnet is more
      important than its diffusive component and than unstirred layers effects which
      are negligible. Therefore group a probes are solvent dragged as they cross the
      epithelium. (ii) There is no correlation between Jnet and Jv for 11 probes with
      dm = 11.8-30 A (group b). Therefore these probes must cross the epithelium by
      diffusion and not by solvent drag. (iii) In a plot of Jnet/Jv vs. dm group a
      probes show a steep linear relation with a slope = -0.111, while for group b
      probes the slope is -0.002. Thus there is a break between groups a and b in this
      plot. We tried to fit the data with models for restricted diffusion and
      convention through cylindrical or parallel slit pathways. We conclude that (i)
      group a probes are dragged by water through an 11.0 A-wide slit. (ii) Most of Jv
      must follow an extracellular noncytosolic pathway. (iii) Group b probes must
      diffuse through a 42 A-wide slit. (iv) A cylindrical pathway does not fit the
      data.

PMID- 8747556
TI  - Cyclic AMP induces rapid increases in gap junction permeability and changes in
      the cellular distribution of connexin43.
AB  - The rapid effects of cAMP on gap junction-mediated intercellular communication
      were examined in several cell types which express different levels of the gap
      junction protein, connexin43 (Cx43), including immortalized rat hepatocyte and
      granulosa cells, bovine coronary venular endothelial cells, primary rat
      myometrial and equine uterine epithelial cells. Functional analysis of changes in
      junctional communication induced by 8-bromo-cAMP was monitored by a fluorescence
      recovery after photobleaching assay in subconfluent cultures in the presence or
      absence of 1.0 mM 1-octanol (an agent which uncouples cells by closing gap
      junction channels). Communicating cells treated with 1.0 mM 8-bromo-cAMP alone
      exhibited significant increases in the percent of fluorescence recovery which
      were detected within 1-3 min depending on cell type, and junctional communication
      remained significantly elevated for up to 24 hr. Addition of 1.0 mM 8-bromo-cAMP
      to cultured cells, which were uncoupled with 1.0 mM octanol for 1 min, exhibited
      partial restoration of gap junctional permeability beginning within 3-5 min.
      Identical treatments were performed on cultures that were subsequently processed
      for indirect immunofluorescence to monitor Cx43 distribution. The changes in
      junctional permeability of cells correlated with changes in the distribution of
      immunoreactive Cx43. Cells treated for 2 hr with 10 microM monensin exhibited a
      reduced communication rate which was accompanied by increased vesicular
      cytoplasmic Cx43 staining and reduced punctate surface staining of junctional
      plaques. Addition of 1.0 mM 8-bromo-cAMP to these cultures had no effect on the
      rate of communication or the distribution of Cx43 compared to cultures treated
      with monensin alone. These data suggest that an effect of cyclic AMP on Cx43 gap
      junctions is to promote increases in gap junctional permeability by increasing
      trafficking and/or assembly of Cx43 to plasma membrane gap junctional plaques.

PMID- 8747557
TI  - Modifications of current properties by expression of a foreign potassium channel
      gene in Xenopus embryonic cells.
AB  - The development of excitable cells is characterized by highly organized patterns
      of expression of ion channels. During the terminal differentiation of Xenopus
      muscle somites, potassium currents are expressed first just after Stage 15 (early
      mid neurula), following a long period during which no voltage-dependent currents
      can be detected in any cell in the dorsal embryo. We have investigated whether
      early expression of a foreign delayed rectifier potassium channel may affect this
      endogenous pattern of electrical development. We injected the purified cRNA of
      the mammalian brain Shaker-like potassium channel, Kv1.1, into fertilized Xenopus
      eggs. The resulting currents were analyzed in blastomeres during a 12-hr period
      prior to Stage 15 and in differentiating muscle cells after Stage 15. In injected
      embryos, a high fraction of blastomeres expressed a delayed rectifier-type
      current. The Kv1.1 current could be distinguished from the endogenous muscle
      delayed potassium current (IK,X) by its very different voltage dependence.
      Separation of currents based on this difference indicated that, in injected
      embryos, IK,X appeared much earlier in development than in control embryos.
      Furthermore, even in cells which expressed solely Kv1.1-type current, the
      sensitivity of the current to dendrotoxin declined dramatically during
      development, approaching that of IK,X. These data suggest an interaction between
      Kv1.1 and endogenous channel subunits, and/or modification of the Kv1.1 protein
      by the embryonic cells in ways not seen in Xenopus oocytes or mammalian cell
      lines.

PMID- 8747558
TI  - The Ca(2+)-induced leak current in Xenopus oocytes is indeed mediated through a
      Cl- channel.
AB  - Defolliculated oocytes of Xenopus laevis responded to removal of external
      divalent cations with large depolarizations and, when voltage clamped, with huge
      currents. Single channel analysis revealed a Cl- channel with a slope conductance
      of about 90 pS at positive membrane potentials with at least four substates.
      Single channel amplitudes and mean channel currents had a reversal potential of
      approximately -15 mV as predicted by the Nernst equation for a channel perfectly
      selective for Cl-. Readdition of Ca2+ immediately inactivated the channel and
      restored the former membrane potential or clamp current. The inward currents were
      mediated by a Ca2+ inactivated Cl- channel (CaIC). The inhibitory potency of Ca2+
      was a function of the external Ca2+ concentration with a half maximal blocker
      concentration of about 20 microM. These channels were inhibited by the Cl-
      channel blockers flufenamic acid, niflumic acid and diphenylamine-2-carboxylate
      (DPC). In contrast, 4,4'-acetamido-4'-isothiocyanatostilbene-2, 2'-disulfonicacid
      (SITS), another Cl- channel blocker, led to activation of this Cl- channel. Like
      other Cl- channels, the CaIC was activated by cytosolic cAMP. Extracellular ATP
      inhibited the channel while ADP was without any effect. Injection of phorbol 12
      myristate 13-acetate (PMA), a protein kinase C activating phorbol ester,
      stimulated the Cl- current. Cytochalasin D, an actin filament disrupting
      compound, reversibly decreased the clamp current demonstrating an influence of
      the cytoskeleton. The results indicate that removal of divalent cations activates
      Cl- channels in Xenopus oocytes which share several features with Cl- channels of
      the CLC family. The former so-called leak current of oocytes under divalent
      cation-free conditions is nothing else than an activation of Cl- channels.

PMID- 8747559
TI  - Reconstitution of a passive Ca(2+)-transport pathway from the basolateral plasma
      membrane of rat parotid gland acinar cells.
AB  - We have previously reported that rat parotid gland basolateral plasma membrane
      vesicles (BLMV) have a relatively high affinity Ca2+ transport pathway and an
      unsaturable Ca2+ flux component (Lockwich et al., 1994. J. Membrane Biol. 141:289
      296). In this study, we have solubilized BLMV with octylglucoside (1.5%) and have
      reconstituted the solubilized proteins into proteoliposomes (PrL) composed of E.
      coli bulk phospholipids, by using a detergent dilution method. PrL exhibited 3-5
      fold higher 45Ca2+ influx than control liposomes (without protein). Ca2+ uptake
      into PrL was dependent on the [protein] in PrL and steady state [Ca2+] in PrL was
      in equilibrium with external [Ca2+]. These data demonstrate that a passive,
      protein-mediated Ca2+ transport has been reconstituted from BLMV into PrL. 45Ca2+
      influx into liposomes did not saturate with increasing [Ca2+] in the assay
      medium. In contrast, PrL displayed saturable 45Ca2+ influx and exhibited a single
      Ca2+ flux component with an apparent KCa = 242 +/- 50.9 microM and Vmax = 13.5 +/
      1.14 nmoles Ca2+/mg protein/ minute. The KCa of Ca(2+)-transport in PrL was
      similar to that of the high affinity Ca2+ influx component in BLMV while the Vmax
      was about 4-fold higher. The unsaturable Ca2+ flux component was not detected in
      PrL. 45Ca2+ influx in PrL was inhibited by divalent cations in the order of
      efficacy, Zn2+ > Mn2+ > Co2+ = Ni2+, and appeared to be more sensitive to lower
      concentrations of Zn2+ than in BLMV. Consistent with our observations with BLMV,
      the carboxyl group reagent N,N'-dicyclohexylcarbodiimide (DCCD) inhibited the
      reconstituted Ca2+ transport in PrL. Importantly, in both BLMV and PrL, DCCD
      induced a 40-50% decrease in Vmax of Ca2+ transport without an alteration in KCa.
      These data strongly suggest that the high affinity, passive Ca2+ transport
      pathway present in BLMV has been functionally reconstituted into PrL. We suggest
      that this approach provides a useful experimental system towards isolation of the
      protein(s) involved in mediating Ca2+ influx in the rat parotid gland basolateral
      plasma membrane.

PMID- 8747560
TI  - Membrane stretch augments the cardiac muscarinic K+ channel activity.
AB  - Arachidonic acid has been shown to activate K(+)-selective, mechanosensitive ion
      channels in cardiac, neuronal and smooth muscle cells. Since the cardiac G
      protein (GK)-gated, muscarinic K+ (KACh) channel can also be activated by
      arachidonic acid, we investigated whether the KACh channel was also sensitive to
      membrane stretch. In the absence of acetylcholine (ACh), KACh channels were not
      active, and negative pressure failed to activate these channels. With ACh (10
      microM) in the pipette, applying negative pressure (0 to -80 mm Hg) to the
      membrane caused a reversible, pressure-dependent increase in channel activity in
      cell-attached and inside-out patches (100 microM GTP in bath). Membrane stretch
      did not alter the sensitivity of the KACh channel to GTP. When GK was maximally
      activated with 100 microM GTP gamma S in inside-out patches, the KACh channel
      activity could be further increased by negative pressure. Trypsin (0.5 mg/ ml)
      applied to the membrane caused activation of the KACh channel in the absence of
      ACh and GTP; KACh channel activity was further increased by stretch. These
      results indicate that the atrial muscarinic K+ channels are modulated by stretch
      independently of receptor/G protein, probably via a direct effect on the channel
      protein/ lipid bilayer.

PMID- 8747561
TI  - Time to peak effect of neostigmine at antagonism of atracurium- or vecuronium
      induced neuromuscular block.
AB  - STUDY OBJECTIVE: (1) To determine the time to peak effect of neostigmine (time to
      peak antagonism) during atracurium- or vecuronium-induced neuromuscular block;
      and (2) to determine the effect on time to peak effect of neostigmine during
      atracurium-induced neuromuscular block, when the dose of neostigmine is increased
      from 35 micrograms/kg to 70 micrograms/kg. DESIGN: Prospective, randomized
      clinical study. SETTING: Gynecologic operating room suite at a university
      hospital. PATIENTS: 45 ASA I and II women admitted for gynecologic laparotomy.
      INTERVENTIONS: Anesthesia was performed with thiopental sodium, fentanyl,
      halothane, nitrous oxide, and atracurium or vecuronium. Train-of-four (TOF)
      stimulation and mechanomyography were used to monitor neuromuscular transmission.
      Neostigmine was administered while a constant degree of neuromuscular block was
      maintained at a twitch height at a point between 4% and 11% of the control twitch
      height, using a continuous infusion of atracurium or vecuronium. The patients
      were randomized to three groups, with 15 patients in each group. Group 1 received
      atracurium block antagonized with neostigmine 35 micrograms/kg; group 2 received
      vecuronium block antagonized with neostigmine 35 micrograms/kg; and group 3
      received atracurium block antagonized with neostigmine 70 micrograms/kg.
      MEASUREMENTS AND MAIN RESULTS: The degree of neuromuscular block at antagonism
      was similar in the three groups. Time to peak effect (mean +/- SD) on TOF ratio
      was significantly longer in Group 1 (9.7 +/- 3.0 minutes) versus Group 2 (6.6 +/-
      1.4 minutes; (p < 0.05). The time to peak effect on TOF ratio during atracurium
      induced block was reduced from 9.7 +/- 3.0 minutes to 6.3 +/- 2.0 minutes when
      the dose of neostigmine was increased from 35 micrograms/kg to 70 micrograms/kg
      (p < 0.05). The peak effect on TOF ratio was significantly greater in Group 3
      compared with Group 1 (p < 0.05), while it was similar in groups 1 and 2.
      CONCLUSION: The time to peak effect of neostigmine 35 micrograms/kg is about 6 to
      10 minutes when antagonizing a constant degree of atracurium- or vecuronium
      induced neuromuscular block at a twitch height at a point between 4% and 11%.
      Even though the time to peak effect was longer with atracurium than with
      vecuronium, clinically significant differences between the antagonizing effect of
      atracurium versus vecuronium block were not demonstrated. The time to peak effect
      during atracurium-induced block decreased when the dose of neostigmine was
      increased from 35 micrograms/kg to 70 micrograms/kg.

PMID- 8747562
TI  - Low-dose caudal morphine for postoperative analgesia in infants and children: a
      report of 500 cases.
AB  - STUDY OBJECTIVE: To determine the effectiveness of morphine 0.03 mg/kg or 0.04
      mg/kg administered caudally to children for postoperative pain relief. DESIGN:
      Retrospective chart review. SETTING: University-affiliated hospital. PATIENTS:
      The charts of 500 children who had undergone various surgical procedures and who
      were given caudal morphine 0.03 mg/kg or 0.04 mg/kg either prior to the surgical
      procedure or immediately at the conclusion of the surgical procedure.
      MEASUREMENTS AND MAIN RESULTS: Parameters of respiratory rate, oxygen saturation,
      nausea and vomiting, voiding problems, and pruritus were recorded for each
      patient. There was no respiratory depression noted in the review of the 500
      patients; 23% had nausea and vomiting, 3% had voiding problems needing bladder
      catheterization, and 7% reported pruritus, which was treated with either
      diphenhydramine or naloxone. CONCLUSION: Statistically there were no differences
      between morphine 0.03 mg/kg and morphine 0.04 mg/kg in all the study parameters.
      There was no respiratory depression in the 500 cases reviewed. The postoperative
      pain relief ranged from 6 hours to over 24 hours. This method of immediate
      postoperative pain management proved to be effective and safe.

PMID- 8747563
TI  - Recovery from mivacurium-induced neuromuscular blockade after neurosurgical
      procedures of long duration.
AB  - STUDY OBJECTIVE: To determine if recovery following prolonged (5 hours in length
      or greater) infusions of mivacurium is different from recovery after single bolus
      administration. DESIGN: open-labelled, controlled study. SETTING: Inpatient
      neurosurgical service at a university hospital. PATIENTS: 36 patients between the
      ages of 18 to 65 without significant history of renal, hepatic, cardiac, or
      metabolic disease undergoing neurosurgical procedures. 21 patients had
      craniotomies or skull base procedures of an estimated length of 5 hours or
      greater; 15 patients (control) underwent short neurosurgical operations (two
      hours or less). INTERVENTIONS: Intravenous (IV) mivacurium 0.15 mg/kg was given
      with stable general anesthesia with 70% nitrous oxide in oxygen, 0.2% to 0.3% end
      tidal isoflurane, and continuous infusion of fentanyl. The control group was
      allowed to recover spontaneously after single bolus administration while
      neuromuscular blockade was maintained in the study group with a continuous
      infusion of mivacurium until 30 minutes before completion of surgery, at which
      time the infusion was discontinued and neuromuscular function was allowed to
      recover spontaneously. MEASUREMENTS AND MAIN RESULTS: The evoked compound
      electromyogram of the adductor pollicis brevis muscle was measured during
      stimulation of the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals.
      Measurements included time to 50% and 90% depression of twitch (T1 of the TOF
      response), time to T1 equal to 25% (T1(25)), 50% (T1(50)), and 75% (T1(75)) of
      baseline, and TOF ratio (TR) at 10%, 25%, 50%, and 75% recovery. Recovery index
      (RI), which is T1(75) minus T1(25), was also determined. All mivacurium infusion
      rates decreased during surgery. Recovery rates were significantly longer in the
      long infusion (LI) group than the control group. RI was also increased in the LI
      group compared with the single bolus control (11.3 +/- 1.2 minutes vs. 7.1 +/-
      0.8 minutes p < 0.05). CONCLUSIONS: Recovery following mivacurium by prolonged
      continuous infusion was slower than that observed after single bolus
      administration in this patient population. Clinically, this increased time to
      recovery may be insignificant.

PMID- 8747564
TI  - Laparoscopic pelvic lymphadenectomy during epidural anesthesia.
AB  - This report describes the perioperative management of a 70-year-old man
      undergoing bilateral pelvic lymphadenectomy. Because of concerns regarding this
      patient's high risk for myocardial ischemia, the four-hour surgical procedure,
      which included the formation of pneumoperitoneum, was performed during epidural
      anesthesia with minimal sedation. The anesthetic implications of pneumoperitoneum
      during regional anesthesia are discussed.

PMID- 8747565
TI  - Neuroleptic malignant syndrome postoperative onset due to levodopa withdrawal.
AB  - Neuroleptic malignant syndrome is a potentially fatal disorder that may develop
      in the perioperative period. A case is described in which discontinuation of
      chronic levodopa therapy precipitated the postoperative development of this
      syndrome. The differential diagnosis and management principles are reviewed.

PMID- 8747566
TI  - The etiology and management of inadvertent perioperative hypothermia.
AB  - Mild perioperative hypothermia is a frequent complication of anesthesia and
      surgery. Core temperature should be monitored during general anesthesia and
      during regional anesthesia for large operations. Reliable sites of core
      temperature monitoring include the tympanic membrane, nasopharynx, esophagus,
      bladder, rectum, and pulmonary artery. The skin surface is not an acceptable site
      for monitoring core temperature. Anesthetic-induced vasodilation initially
      rapidly decreases core temperature secondary to an internal redistribution of
      heat rather than an increased heat loss to the environment. Both general and
      regional anesthetics impair thermoregulation, increasing the interthreshold
      range; that is, the range of core temperatures over which no autonomic response
      to cold or warmth occurs. Preinduction skin surface warming is the only means to
      prevent this initial redistribution hypothermia. Forced-air warming is the most
      effective method of rewarming hypothermic patients intraoperatively.

PMID- 8747567
TI  - Anesthesia crisis resource management: real-life simulation training in operating
      room crises.
AB  - Little formal training is provided in anesthesiology residency programs to help
      acquire, develop, and practice skills in resource management and decision making
      during crises in practice. Using anesthesia crisis resource management (ACRM)
      principles developed at another institution, 68 anesthesiologists and 4 nurse
      anesthetists participated in an ACRM training course held over a 2 and a half
      month period. The anesthesia environment was recreated in a real operating room,
      with standard equipment and simulations requiring actual performance of clinical
      interventions. Scenarios included overdose of inhalation anesthetic, oxygen
      source failure, cardiac arrest, malignant hyperthermia, tension pneumothorax, and
      complete power failure. A detailed questionnaire was administered following the
      debriefing and completed by all participants, documenting their immediate
      impressions. Participants rated themselves as having performed well in the
      simulator. Senior attendings and residents rated themselves more highly than did
      their junior counterparts. The potential benefit of this course for
      anesthesiologists to practice anesthesia more safely in a controlled exercise
      environment, was rated highly by both groups. Over one half of respondents in all
      categories felt that the course should be taken once every 12 months; another
      third of each group felt that the course should be taken once every 24 months.
      While no senior attendings believed that the course should be taken once every 6
      months, approximately 10% of respondents in other categories that it should. Of
      respondents in the senior and junior attending category, 5% felt the course
      should never be taken. Although attendings were less favorable than residents in
      their rating of the value of the course, both groups were still enthusiastic.

PMID- 8747568
TI  - Reflective blankets and intraoperative heat conservation.

PMID- 8747569
TI  - Preparing for the unanticipated difficult airway.

PMID- 8747570
TI  - Emergency use of the laryngeal mask airway during helicopter transfer of a
      neonate.

PMID- 8747571
TI  - Antifibrinolytic therapy: treat whom and with what?

PMID- 8747572
TI  - Congenital triangular alopecia (Brauer nevus).
AB  - Congenital triangular alopecia is manifested at 3 to 5 years of age by unilateral
      or, less frequently, bilateral patches of alopecia in the frontotemporal region.
      At this age the differential diagnosis is important, particularly as regards
      alopecia areata. Only about 47 cases have been reported, probably because the
      lesion is benign and nonprogressive. In 6200 patients seen in index visits, we
      found 7 with triangular alopecia, a frequency of 0.11%. We believe that males do
      not require treatment because of the later development of androgenic alopecia,
      but in women, surgical treatment is successful.

PMID- 8747573
TI  - Extramediastinal bronchogenic cysts in children.
AB  - Three children with subcutaneous masses were found to have extramediastinal
      bronchogenic cysts. The suprasternal area is by far the most common location of
      this highly unusual embryonic rest cyst. In one of our patients a cyst was
      located in the scapular region, which is a particularly rare site. To date only
      41 subcutaneous bronchogenic cysts have been reported. Preoperative diagnosis is
      difficult, although the presence of clear mucoid material within the cyst may
      suggest the diagnosis. The histologic presence of ciliated, pseudostratified,
      columnar or cuboidal epithelium, mucus-secreting glands, smooth muscles, and
      occasional cartilage establishes the diagnosis.

PMID- 8747574
TI  - Subepidermal calcified nodule in children: a clinicopathologic study of 21 cases.
AB  - Twenty-one cases of subepidermal calcific nodule are presented. These lesions
      occur twice as commonly in males compared to females, with the head (particularly
      the ear), and neck as favored locations. No case was identified correctly
      clinically and only 1 case had a history of trauma, which appeared unrelated to
      the lesion. Histologically, there was a variety of appearances, with two-thirds
      of specimens exhibiting a warty architecture. Younger lesions were composed of
      large, amorphous, calcific dermal deposits and were frequently associated with
      epidermal ulceration. The older lesions were not ulcerated and the calcium
      deposits were in small spherules. There was no evidence of pilomatrixoma or pre
      existing nevus. It is hypothesized that subepidermal calcified nodule represents
      dystrophic calcification secondary to dermal injury-several in our series showed
      the architectural changes of verruca vulgaris.

PMID- 8747575
TI  - Acute graft-versus-host disease with unusual cutaneous intracellular vacuolation
      in an infant with severe combined immunodeficiency.
AB  - We report an infant with severe combined immunodeficiency (SCID) who had
      cutaneous manifestations of acute graft-versus-host disease (GVHD) due to
      maternofetal lymphocyte engraftment. Histologic and ultrastructural examinations
      of the skin revealed intracellular vacuoles resembling lipid droplets in the
      epidermis and dermis, which is not a recognized feature of acute GVHD or SCID.

PMID- 8747576
TI  - Henoch-Schonlein purpura presenting as hemorrhagic vesicles and bullae: case
      report and literature review.
AB  - Henoch-Schonlein purpura is a syndrome characterized by nonthrombocytopenic
      purpura accompanied by arthralgia, gastrointestinal symptoms, or renal
      involvement. We report a 5.5-year-old boy with high fever and hemorrhagic
      vesicles and bullae varying in size from 2 to 50 mm in diameter, on both pinnas,
      the hard palate, gums, dorsa of the hands, buttocks, and both legs, and review
      the pertinent literature.

PMID- 8747577
TI  - Linear porokeratosis presenting as erosions in the newborn period.
AB  - The classic appearance of porokeratosis is characterized by a hyperkeratotic
      annular rim that expands peripherally, leaving an atrophic center. Linear
      porokeratosis is a variant with collections of such lesions arranged in a linear
      fashion, usually corresponding to a dermatome or Blaschko's lines. Ulcerations
      have rarely been reported in patients with porokeratosis. We report an unusual
      case of linear porokeratosis at birth, with erosions and ulcerations of the face
      and lower extremity, that eluded diagnosis for nearly a year. Porokeratosis
      should be considered in the differential diagnosis of erosions in the newborn
      period.

PMID- 8747578
TI  - Acanthosis nigricans: a marker for hyperinsulinemia.
AB  - A 12-year-old girl developed acanthosis nigricans due to increased levels of
      serum insulin. Hyperinsulinemia has been recognized as the underlying cause in
      most cases of acanthosis nigricans. In this paper we outline a typical clinical
      case with special regard to the proposed pathogenesis.

PMID- 8747579
TI  - Childhood subacute cutaneous lupus erythematosus associated with homozygous
      complement 2 deficiency.
AB  - We describe a 9-year-old boy with an Ro-positive, subacute, cutaneous lupus rash
      associated with homozygous C2 deficiency. His response to a mild topical steroid
      and sunscreen was excellent. Hereditary complement deficiency and its association
      with childhood lupus erythematosus are discussed.

PMID- 8747580
TI  - Multiple familial pilomatricomas: a cutaneous marker for Gardner syndrome?
AB  - A 40-year-old man and his 6-year-old only son had numerous, firm papulonodular
      lesions on their faces. Their medical histories were unremarkable and no family
      consanguinity was recorded. Surgical excision of several lesions was performed on
      each patient. All the lesions were solid tumors with the characteristic
      histopathologic features of pilomatricoma. A gastrointestinal radiologic and
      fibroscopic survey disclosed numerous adenomatous colonic polyps in the father.
      Additional studies revealed that he also had minor dental abnormalities, a small
      osteoma on the right mandible, and unilateral, ocular, pigmented retinal macules.
      The diagnosis of multiple adenomatous colonic polyposis was established only
      after the well-known association of pilomatricoma-like changes in epidermal cysts
      in patients with Gardner syndrome was considered. Possibly, multiple familial
      pilomatricomas could be considered a cutaneous marker of Gardner syndrome.

PMID- 8747581
TI  - Congenital ventral hernia in association with focal dermal hypoplasia.
AB  - Focal dermal hypoplasia is a rare, X-linked dominant syndrome characterized by
      dysplasia of the skin, skeleton, and central nervous system. We report an infant
      who was born with severe focal dermal hypoplasia and an epigastric hernia.
      Operative timing and approach to abdominal wall defects in the presence of severe
      cutaneous dysplasia are discussed.

PMID- 8747582
TI  - Late, painful, subungual hyperkeratosis in incontinentia pigmenti.
AB  - The postpubertal appearance of subungual, painful keratotic tumors is a rare
      feature of incontinentia pigmenti. A patient affected by incontinentia pigmenti
      developed subungual, painful, nontumoral, hyperkeratotic lesions of the hands at
      10 years of age. The mildness of the subungual lesions may be explained by the
      early stage of the disorder, but it is difficult to correlate the severity of the
      fingertip pain with the absence of true tumoral swelling. To our knowledge this
      is the youngest patient reported so far and the only one with a prepubertal
      expression of this puzzling disorder.

PMID- 8747583
TI  - Solid alveolar rhabdomyosarcoma of the hand in adolescence: a clinical,
      histologic, immunologic, and ultrastructural study.
AB  - Rhabdomyosarcoma (RMS), a high-grade, malignant, skeletal muscle tumor,
      represents approximately 5% of neoplasms in children. The poorly differentiated
      forms of RMS are often not easily diagnosed and classified. Among the four
      histologic variants, alveolar RMS is the least frequently reported subtype. A
      poorly differentiated solid variant of alveolar RMS occurred on the right hand of
      a 16-year-old girl. Because of the tumor size, local invasiveness, and occurrence
      of cutaneous and breast metastases at presentation, the clinical staging was
      group IV (T2/NO/M1). Surgical excisions of the primary and metastatic locations
      were performed and chemotherapy with vincristine, dactinomycin, cyclophosphamide,
      and doxorubicin was administered. Light and electron microscopy studies revealed
      a solid proliferation with a focal alveolar pattern of monomorphous, small, round
      neoplastic cells without easily detectable muscular morphologic features. The
      skeletal muscle origin was revealed by the positive immunostaining for desmin,
      alpha-sarcomeric actin, muscle-specific actins, and enolase, and confirmed by
      immunoblotting for desmin. Despite the age of our patient, which is considered by
      some authors an independent predictor of outcome, all prognostic variables were
      unfavorable. However, a disease-free interval during three years of follow-up
      underlines the importance of multidisciplinary regimens for the treatment of this
      rare solid tumor of childhood and adolescence.

PMID- 8747584
TI  - Cutis marmorata telangiectatica congenita associated with a double aortic arch.
AB  - We report a patient with cutis marmorata telangiectatica with the hitherto
      unreported anomaly of a double aortic arch. The presence of two major vascular
      anomalies in this patient may be secondary to a developmental defect of the
      mesoderm during embryogenesis.

PMID- 8747585
TI  - Erythrokeratodermia variabilis present at birth: case report and review of the
      literature.
AB  - A healthy boy had the distinctive lesions of erythrokeratodermia variabilis (EKV)
      at birth. Twenty-eight patients described in the literature had EKV that
      presented in childhood. Nine of the 28 were said to have had a rash since birth,
      but none were distinctive of EKV. To our knowledge this is the first well
      documented case describing a child born with the skin manifestations of EKV. We
      conclude that patients with EKV are infrequently born with a rash, and that only
      very rarely when the rash is present is it suggestive of the disorder.

PMID- 8747586
TI  - Congenital cutaneous candidiasis: case report and review.
AB  - This report describes a preterm infant with congenital cutaneous candidiasis
      associated with paronychia, dystrophy of the nail plates, and marked, transient
      leukocytosis.

PMID- 8747588
TI  - Cutaneous presentation of juvenile chronic myelogenous leukemia: a diagnostic and
      therapeutic dilemma.
AB  - Annular, erythematous, circinate plaques were the first manifestation of juvenile
      chronic myelogenous leukemia (JCML) in an otherwise healthy 2.5-year-old boy who
      had had these lesions since 6 months of age. The lesions showed an atypical
      hematopoietic infiltrate on biopsy. Biopsy of a bone marrow specimen and
      peripheral blood smear were normal six months before leukemic transformation. At
      3 years of age the boy developed splenomegaly, thrombocytopenia, and petechiae,
      and a bone marrow aspirate and cell marker studies were regarded as consistent
      with, if not diagnostic of, JCML. Four previous cases of cutaneous leukemic
      infiltrate associated with JCML have been published. Our patient had recurring
      urticarial-like plaques for two years before the initial bone marrow finding of
      JCML. Given the poor prognosis and progressively evolving course of JCML, it may
      be appropriate to consider therapy before bone marrow changes, based on the
      presence of the cutaneous eruption with the appropriate findings on skin biopsy
      and an elevated fetal hemoglobin.

PMID- 8747587
TI  - Cutaneous congenital candidiasis: a case report.
AB  - Candida albicans is a frequent pathogen of the female genital tract, especially
      during pregnancy. Congenital candidiasis can occur as cutaneous or disseminated
      infection. We report a case of congenital cutaneous candidiasis, which may occur
      more frequently than is indicated by the literature. This is followed by a
      discussion of the pathogenesis, clinical presentation, diagnosis, and treatment
      of this infection.

PMID- 8747589
TI  - Cutaneous candidiasis.

PMID- 8747590
TI  - What syndrome is this? Hunter syndrome (mucopolysaccharidosis II).

PMID- 8747591
TI  - Ecchymoses and edema in a 4-month-old boy.

PMID- 8747592
TI  - Proceedings of the Society for Pediatric Dermatology meeting, June 29-July 1,
      1995, Vancouver, British Columbia, Canada.

PMID- 8747593
TI  - Effect of topical calcipotriol on inflammatory linear verrucous epidermal nevus.

PMID- 8747594
TI  - A case of FG syndrome with gingival hyperplasia and keloids.

PMID- 8747595
TI  - Infrequent somatic mutations of the p16 and p15 genes in human bladder cancer:
      p16 mutations occur only in low-grade and superficial bladder cancers.
AB  - A recently identified gene, p16, located on chromosome 9p21, has been shown to be
      deleted and/or mutated in various types of human cancers. To investigate
      structural alterations of p16 and a neighboring gene, p15, we examined human
      bladder cancers for mutations in the entire coding region of these genes using
      polymerase chain reaction and single-strand conformational polymorphism analysis.
      Of 50 samples obtained from patients with bladder cancer, 3 (6%), all low-grade
      and superficial tumors, were found to have p16 gene alterations. The alterations
      included 1 missense mutation and 2 single-base deletions. We found no p15 gene
      mutations in these 50 bladder cancers. Our results suggested that p16 gene
      mutations, although they occurred at low frequency, are involved in some low
      grade and early stage bladder cancers.

PMID- 8747596
TI  - Immunohistochemical detection of p53 in melanomas with rare p53 gene mutations is
      associated with mdm-2 overexpression.
AB  - Expression of mutant p53 detected by immunohistochemistry has been described in
      human malignant melanoma, but there are few reports of molecular analyses. To
      investigate the genetic basis for p53 expression in malignant melanoma, we
      examined 58 primary tumors and 5 cutaneous metastases. The entire coding sequence
      of the p53 gene was screened by single-strand conformation polymorphism analysis
      and direct genomic sequencing of polymerase chain reaction products. p53 and mdm
      2 expression were studied by immunohistochemistry. Two p53 gene mutations could
      be found in 1/63 samples examined, both having occurred in the same specimen from
      a patient with a nodular melanoma. p53 and mdm-2 expression were found
      immunohistochemically to increase with tumor progression both in frequency and in
      the mean proportion of positive cells, with the same cases staining positively
      for both antibodies. Our results suggest that a) p53 gene mutations are a rare
      event in human melanoma; b) accumulation and thus immunohistochemically
      detectable expression of p53 may result from posttranslational mechanisms
      affecting the p53 gene product; and c) p53 and mdm-2 are more important in late
      events in melanoma carcinogenesis.

PMID- 8747597
TI  - Combination of anti-cell adhesive synthetic Arg-Gly-Asp-Ser analogue and
      anticancer drug doxorubicin heightens their original antimetastatic activities.
AB  - A new compound containing the cell-adhesive Arg-Gly-Asp-Ser (RGDS) peptide was
      synthesized, i.e. tetrahydrofurantetracarboxylic acid (THFTCA)-RGDS conjugate
      [THFTCA- (RGDS)3, FC-243], and the inhibitory effect of FC-243 on lung metastasis
      of B16-BL6 melanoma in mice was examined in combination with or without the
      anticancer agent doxorubicin (DOX). FC-243 showed an inhibitory effect on lung
      metastasis of melanoma cells in a dose-dependent manner. A mixture of THFTCA and
      RGDS peptide or THFTCA alone did not show any inhibitory effect on experimental
      lung metastasis as compared with FC-243 on a molar basis. RGDS peptide, however,
      required a higher dose to obtain a sufficient antimetastatic effect. Intermittent
      IV administration of FC-243 after the inoculation of B16-BL6 cells caused
      significant inhibition of spontaneous lung metastasis as compared with multiple
      administration of RGDS or untreated control. The in vitro tumor invasion study
      showed that FC-243 as well as RGDS+THFTCA on a molar basis resulted in similar
      inhibition of the invasion of B16-BL6 cells into reconstituted basement membrane
      Matrigel. Combined treatment with FC-243 and DOX significantly inhibited lung
      metastasis of melanoma as compared with either treatment alone or the untreated
      control. Administrations of FC-243 and DOX in combination substantially prolonged
      the survival time of mice. These results demonstrate that combination therapy of
      the anti-cell adhesive FC-243 and the anticancer agent DOX, i.e. antiadhesion
      therapy and chemotherapy, is a new approach that offers enhanced inhibitory
      effects on tumor metastasis and invasion.

PMID- 8747598
TI  - C-JUN/AP-1 as possible mediators of tumor necrosis factor-alpha-induced apoptotic
      response in mouse JB6 tumor cells.
AB  - Sensitivity to cell killing by tumor necrosis factor (TNF)-alpha was seen in the
      JB6-derived transformed mouse RT101 cell variants previously described as
      resistant to 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced killing, while
      the TPA-sensitive variants were resistant to killing by TNF-alpha. Morphological
      and biochemical changes characteristic of apoptosis were found to precede TNF
      alpha-induced cell death in TNF-alpha-sensitive (TNFs) but not TNF-alpha
      resistant (TNFr) cells. In TNFr cells, TNF-alpha increased the cell cycle rate.
      The onset of cellular damage in TNFs cells, as indicated by propidium iodide
      uptake, was seen as early as 6 h after TNF-alpha treatment. 4,6-diamidino-2
      phenylindole staining revealed chromosomal condensation approximately 4-6 h after
      TNF-alpha treatment. The DNA oligonucleosomal ladder of 180 bp and its multiples,
      a characteristic feature of apoptosis, was seen at 48 h. Little or no significant
      differences were found in the basal or induced levels of mRNA expression of
      several potential apoptosis mediator genes or apoptosis inhibitor genes. A
      dephosphorylated species of anti-c-Jun immunoprecipitated protein appeared in
      TNFs cells at 3 h posttreatment, accompanied by a parallel increase in AP-1
      activity. Higher constitutive levels of the antioxidant enzymes superoxide
      dismutase and catalase were found in TNFr cells, but TNF-alpha did not
      significantly affect the activities of these enzymes or differentially induce
      their expression. The findings suggest that the preferential and transient
      increase in c-Jun dephosphorylation and AP-1 transcriptional activity may
      contribute to the preferential apoptotic response in TNFs cells; and that the
      greater constitutive oxidant defense in TNFr cells may contribute to their
      resistance.

PMID- 8747600
TI  - Influence of pH on the cytotoxicity of cisplatin in EMT6 mouse mammary tumor
      cells.
AB  - Pathophysiological factors exist within solid tumors that lead to a low pH
      environment. Therefore, pH-sensitive cancer chemotherapeutic agents may
      selectively target and kill tumor cells while sparing the normal tissue from
      toxicity. Using colony forming assays to assess cell survival, we found that EMT6
      mouse mammary tumor cells were more sensitive to cisplatin cytotoxicity when
      cultured in pH 6.0 medium than in pH 7.2, 6.8, or 6.4 medium. The pH-dependent
      cytotoxicity of cisplatin resulted from an increase in cisplatin accumulation and
      an increase in the amount of DNA cross-links at pH 6.0 compared with pH 7.2.
      Because DNA is the cytotoxic target of cisplatin, intracellular pH (pHi) may be
      an important factor in determining the cytotoxicity of anticancer drugs at low
      extracellular pH (pHe). Therefore, manipulating the pHi of cells could be one
      method to enhance the effectiveness of the pH-sensitive chemotherapeutic agents.
      The pHi of EMT6 cells varied with pHe: at pHe 7.2, pHi was 7.54; at pHe 6.8, pHi
      was 7.29; at pHe 6.4, pHi was 7.02; and at pHe 6.0, pHi was 6.64. Using
      inhibitors to the ion transport mechanisms which regulate pHi, 5-N,N
      hexamethylene amiloride (NHMA) and 4-acetamido-4'-isothiocyanostilbene-2,2'
      disulfonic acid (SITS), the pHi and pHe of EMT6 cells were equilibrated. To
      evaluate the importance of pHi in determining drug toxicity, cell survival was
      determined for cells treated with cisplatin in the presence of NHMA and SITS.
      Cells cultured with NHMA and SITS were less sensitive to cisplatin. The cisplatin
      resistance obtained was independent of pH and could be attributed to the presence
      of SITS.

PMID- 8747599
TI  - Inhibitors of intracellular pH regulation induce cisplatin resistance in EMT6
      mouse mammary tumor cells.
AB  - Previous results from this laboratory indicated that EMT6 cells treated with
      inhibitors of the intracellular pH (pHi) regulatory mechanisms were resistant to
      cisplatin (Laurencot, C.M.; Kennedy, K.A. The effect of low pH on the
      cytotoxicity of cisplatin in EMT6 mouse mammary tumor cells. Oncol. Res. 7:371
      380; 1995.) This inhibitor-induced cisplatin resistance was independent of pH.
      The purpose of the research presented here was to characterize further cisplatin
      resistance observed in cells cultured with the Na+/H+ antiport inhibitor 5-(N,N
      hexamethylene) amiloride (NHMA) and the HCO3-/Cl- exchanger inhibitor 4-acetamido
      4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS). Using [195mPt]-DDP, the
      accumulation of cisplatin into EMT6 mouse mammary tumor cells treated with NHMA
      and SITS was not changed. Total DNA cross-link formation and DNA-interstrand
      cross-link formation, however, decreased in NHMA- and SITS-treated cells. Since
      cisplatin accumulation was unchanged in NHMA- and SITS-treated cells but the
      amount of DNA cross-links decreased, the intracellular activation of cisplatin
      appeared to be altered in the cisplatin-resistant cells. Because SITS interferes
      with chloride transport and chloride has been proposed to be involved in
      cisplatin activation, cisplatin toxicity in EMT6 cells was evaluated in chloride
      deficient medium. EMT6 cells cultured in chloride-deficient medium were less
      sensitive to cisplatin than cells cultured in chloride-containing medium, but
      this sensitivity was not altered by NHMA and SITS. Furthermore, the resistance to
      cisplatin in cells treated with NHMA and SITS was similar in chloride-containing
      and chloride-deficient medium. These data suggest that the concentration of other
      ions, in addition to chloride, may be important for cisplatin toxicity.

PMID- 8747601
TI  - Induction of apoptotic DNA fragmentation and c-jun downregulation in human
      myeloid leukemia cells by the permeant Ca2+ chelator BAPTA/AM.
AB  - The permeant Ca2+ chelator acetoxymethyl-1,2-bis(2-aminopheoxy)ethane- N,N,N',N'
      tetraacetic acid (BAPTA/AM), an agent previously used to characterize drug
      induced apoptosis in neoplastic cells, has been examined with respect to
      induction of DNA fragmentation and cytotoxicity in the human leukemia cell lines
      HL-60 and U937. Exposure of cells to various concentrations of BAPTA/AM for 6 h
      resulted in a biphasic induction of internucleosomal DNA cleavage, with maximal
      damage occurring at 10-microM concentrations. Higher BAPTA/AM concentrations were
      associated with the loss of internucleosomal cleavage products, but with the
      appearance of larger (i.e., 50-kilobase) fragments on pulsed-field gel
      electrophoresis. Cells exposed to 10 microM BAPTA/AM exhibited classic apoptotic
      morphology, whereas cells exposed to 50-microM concentrations displayed atypical
      features (e.g., cell swelling, chromatin clumping); in each case, substantial
      cytotoxicity was noted. The actions of BAPTA/AM did not depend upon the presence
      of extracellular Ca2+, nor were they affected by impermeant Ca2+ chelators.
      Measurement of cytosolic Ca2+ by Fura-2/AM or Indo-1 revealed late but not early
      increases in intracellular Ca2+ in BAPTA/AM-treated cells. Finally, BAPTA/AM
      induced apoptosis was accompanied by the concentration-dependent downregulation
      of the immediate early response gene c-jun. These findings suggest a complex role
      for Ca2+ chelators such as BAPTA/AM in the regulation of human myeloid leukemic
      cell apoptosis, and indicate that this agent may selectively antagonize
      internucleosomal DNA fragmentation without interfering with other aspects of the
      apoptotic response and/or cell lethality.

PMID- 8747602
TI  - Hyperthermia-mediated targeted delivery of thermosensitive liposome-encapsulated
      melphalan in murine tumors.
AB  - Targeted drug delivery systems combining thermosensitive liposome-entrapped
      anticancer drugs and hyperthermia have been tried for targeting drugs to tumors.
      These heat-sensitive liposomes are prepared from synthetic lipids. Herein we
      report the use of thermosensitive liposomes composed of natural lipids, viz., egg
      phosphatidyl choline, cholesterol, and ethanol, having phase transition
      temperature of 42.7 degrees C for targeted drug delivery. The antitumor effect of
      melphalan encapsulated in thermosensitive small unilamellar liposomes
      administered in combination with hyperthermia was studied in C57B1/6 mice bearing
      B16F10 melanoma. The in vivo efficacy of liposome-encapsulated melphalan in
      combination with hyperthermia as measured by reduction in tumor volume and
      increased survival time was greater than that of an equivalent concentration of
      free melphalan with or without heating. These results suggest that the
      combination of drug-loaded natural lipid-derived thermosensitive liposomes with
      local hyperthermia at the tumor site could be useful in enhancing drug delivery
      to tumors and improving its therapeutic efficacy in treatment of solid tumors.

PMID- 8747603
TI  - Differential responsiveness of human breast cancer cells to basic fibroblast
      growth factor: a cell kinetics study.
AB  - The effects of basic fibroblast growth factor (bFGF) on breast cancer cells are
      still contradictory and not fully understood. We have studied the effect of bFGF
      on the cell cycle kinetics of two breast cancer cell lines (MCF-7 and MDA-MB-231)
      and an immortalized cell line (HBL-100). The methodology included use of
      microscopic image analysis with cell numeration, Feulgen staining, Proliferating
      Cell Nuclear Antigen/Ki-67 immunodetection and bromodeoxyuridine incorporation.
      We show that bFGF is mitogenic for MCF-7 cells via a mechanism of recruitment of
      G0 phase cells to reenter into the cell cycle and by decreasing the G1 phase
      length. No effect of bFGF on cell cycle parameters has been found with either
      highly metastatic MDA-MB-231 cells or immortalized HBL-100 cells. These results
      reveal differences in bFGF responsiveness of breast epithelial cells.

PMID- 8747604
TI  - Drastic reduction of topoisomerase II alpha associated with major acquired
      resistance to topoisomerase II active agents but minor perturbations of cell
      growth.
AB  - V511 and V513 cell lines, derived from Chinese hamster V79 cells following
      alkylating agent mutagenesis and subsequent selection with VP-16, showed
      resistance to cytotoxicity and DNA strand breaks induced by topoisomerase (topo)
      II inhibitors and were resistant to VP-16-induced sister chromatid exchanges.
      They showed no amplification of the multidrug-resistant p-glycoprotein. In a
      kinetoplast-DNA decatenation assay, V511 and V513 showed 51% and 49% topo II
      activity relative to parental V79 cells, respectively. By western-blot analysis
      all three logarithmically growing cell lines showed similar levels of topo II
      beta (M(r) 180,000), which increased as cells progressed to quiescence. In
      contrast, immunoreactive levels of topo II alpha (M(r) 170,000) were 6.8% in V511
      and 62.4% in V513 relative to V79. V511 showed drastically decreased topo II
      alpha in both log growth and quiescence. In a second approach, immunoreactive
      topo II was analyzed in different phases of the cell cycle in logarithmically
      growing cells fractionated by fluorescence-activated cell sorting. All cell lines
      demonstrated relatively stable topo II beta throughout the cell cycle. Topo II
      alpha showed little cell cycle variation in V79 or V513. However, in V511, it was
      only detectable at low levels in G2/M phase. When cell growth parameters were
      measured, V511 and V513 showed a 17% increase in cell doubling time relative to
      V79. These studies indicate that cells with a drastic reduction in topo II alpha
      (V511) or mutant topo II alpha (V513) but with normal levels of topo II beta show
      only minor perturbations of cell growth.

PMID- 8747605
TI  - Crash and violation experience of pilots involved in prior commuter and air taxi
      crashes: a historical cohort study.
AB  - BACKGROUND: Commuter flights and air taxis represent a major category of aviation
      losses in terms of both human life and economic resources. Previous studies have
      examined human factors involved in these crashes. A retrospective study revealed
      that pilots' prior crash and violation records are associated with an increased
      risk of being involved in a commuter aircraft or an air taxi crash. HYPOTHESIS:
      Pilots who are involved in crashes are at increased risk of involvement in future
      crashes and violations. METHODS: Pilots who had been involved in and survived
      commuter aircraft or air taxi crashes during 1983-88 (crash group, n = 580) and a
      random sample of pilots who were flying for these commercial operations (control
      group, n = 1555) were followed up for 3 yr. The crash/incident and violation
      experience during the 3 yr of follow-up was compared between the two groups at
      univariate level and at multivariate level. RESULTS: During the 3 yr of follow
      up, the incidence rate of crashes/incidents was significantly higher for the
      crash group than for the control group (12.4% vs. 7.2%, p < 0.01). The crash
      group also was more likely to have a violation record than the control group
      during the 3 yr of follow-up (8.6% vs. 3.7%, p < 0.01). These differences were
      not changed by adjusting for pilot age, total flight time and medical class.
      CONCLUSIONS: Pilots who were involved in commuter aircraft or air taxi crashes
      have significantly higher subsequent crash and violation rates than their
      counterparts. In order to develop effective prevention strategies, environmental
      and psychosocial factors that predispose pilots to increased risk of involvement
      in aviation crashes and violations should be examined.

PMID- 8747606
TI  - Visual performance effects and user acceptance of the M43A1 aviation protective
      mask frontserts.
AB  - BACKGROUND: The initial M43 aviation protective mask was fielded without
      provisions for optical corrective devices. Contact lenses, an interim solution,
      were not entirely acceptable since a small segment of the population could not be
      fitted adequately with contacts. This study evaluated visual performance affects
      and user acceptance of the M43A1 mask with frontsert correction modifications.
      METHODS: The investigation was divided into three phases: 1) a helicopter
      simulator evaluation designed to experimentally test the suitability of the M43A1
      frontserts, both in single vision and bifocal forms, for use in the aviation
      environment; 2) a static cockpit evaluation, designed to identify aircraft
      specific problems with the frontsert system; and 3) an inflight evaluation to
      examine the stability and usability of the frontserts under actual flight
      conditions. The subjects were 30 U.S. Army aviators (28 men and 2 women).
      RESULTS: Objective data from flight simulation evaluations suggested there were
      no significant differences between flight performance with and without the mask,
      despite refractive status. Subjective data from static and flight evaluations
      reflected positive user acceptance of the new mask and frontserts. Problems may
      exist in smaller cockpits (OH-58 A/C, D), but evidence suggested that this may
      have been an artifact resulting from testing the mask while wearing protective
      body armor. CONCLUSIONS: Within the range of flight conditions and profiles
      examined, the M43A1 frontsert system meets U.S. Army aviation needs for optical
      correction when mission requirements dictate flying with chemical-biological
      protective masks.

PMID- 8747607
TI  - Influence of body composition on rewarming from immersion hypothermia.
AB  - BACKGROUND: This study was conducted to determine if the differences between
      efficacies of three treatments for immersion hypothermia are affected by body
      composition. METHODS: Twelve subjects were divided into equally sized low (LF)
      and high (HF) fat groups. On three occasions subjects were each immersed in cold
      water until esophageal temperatures (Tes) decreased to approximately 33.2 degrees
      C (LF) and approximately 35.8 degrees C (HF). They were then rewarmed by: 1)
      shivering; 2) application of external heat; or 3) treadmill exercise in a
      balanced design. RESULTS: For HF, the afterdrop during exercise (1.04 +/- 0.2
      degrees C) was greater than during shivering (0.35 +/- 0.3 degrees C) and
      external heat (0.36 +/- 0.1 degree C) (p < 0.01). In LF, however, the exercise
      afterdrop (0.75 +/- 0.2 degree C) was greater than only external heat (0.35 +/-
      0.2 degree C) (p < 0.05) but not shivering (0.58 +/- 0.4 degree C). There was a
      positive relationship between % fat and afterdrop for the exercise condition with
      a slope (95% C.I.) of 0.03 (0.01 to 0.05) degree C.% fat-1 (r2 = 0.37, p < 0.05).
      The exercise rewarming rate (3.48 +/- 1.1 degrees C.h-1) was greater (p < 0.01)
      than during both shivering (1.80 +/- 0.7 degrees C.h-1) and external heat (2.22
      +/- 0.7 degrees C.h-1) in HF while no difference was seen between the three
      treatments (5.28 +/- 0.4, 4.86 +/- 1.1 and 5.16 +/- 0.7 degrees C.h-1,
      respectively) in LF. There were inverse relationships between % fat and rewarming
      rate in the exercise -0.12 (-0.23 to -0.01) degree C.h-1.% fat-1, (r2 = 0.38),
      shivering -0.27 (-0.38 to -0.16) degrees C.h-1.% fat-1, (r2 = 0.76) and external
      heat -0.26 (-0.35 to -0.17) degree C.h-1.% fat-1, (r2 = 0.83) conditions (p <
      0.05). CONCLUSIONS: The inter-treatment differences between these techniques are
      accentuated in the HF, and attenuated (afterdrop) or even eliminated (rewarming
      rate) in the LF subgroup.

PMID- 8747608
TI  - Regional muscle loss after short duration spaceflight.
AB  - BACKGROUND: Muscle strength and limb girth measurements during Skylab and Apollo
      missions suggested that loss of muscle mass may occur as a result of spaceflight.
      Extended duration spaceflight is important for the economical and practical use
      of space. The loss of muscle mass during spaceflight is a medical concern for
      long duration flights to the planets or extended stays aboard space stations.
      Understanding the extent and temporal relationships of muscle loss is important
      for the development of effective spaceflight countermeasures. HYPOTHESIS: We
      hypothesized that significant and measurable changes in muscle volume would occur
      in Shuttle crewmembers following 8 d of weightlessness. METHODS: MRI was used to
      obtain the muscle volumes of the calf, thigh and lower back before and after the
      STS-47 Shuttle mission. RESULTS: Statistical analyses demonstrated that the
      soleus-gastrocnemius (-6.3%), anterior calf (-3.9%), hamstrings (-8.3%),
      quadriceps (-6.0%) and intrinsic back (-10.3%) muscles were decreased, p < 0.05,
      compared to baseline, 24 h after landing. At 2 weeks post recovery, the
      hamstrings and intrinsic lower back muscles were still below baseline, p < 0.05.
      CONCLUSIONS: These results demonstrate that even short duration spaceflight can
      result in significant muscle atrophy.

PMID- 8747609
TI  - Efficacy of a portable acustimulation device in controlling seasickness.
AB  - BACKGROUND: Nausea and vomiting caused by motion sickness are serious and
      sometimes debilitating symptoms for commercial and recreational seafarers.
      HYPOTHESIS: In order to treat these symptoms, a portable device, the Relief Band,
      was designed to deliver acustimulation to the Neiguan (P6) acupuncture point.
      METHOD: Nine volunteers used the device on a placebo point or the P6 active point
      on the open seas outside the San Francisco Bay. Motion sickness symptoms were
      graded from 1 ("feel fine") to 5 ("intermittent vomiting, with or without
      nausea"). RESULTS: Five subjects with motion sickness initially positioned the
      device at the placebo site and reported minimal symptom improvement (3.6 +/- 0.6
      to 3.4 +/- 1.1) (mean, +/- SD), whereas the other four subjects initially used
      the device in the P6 position and reported decreased symptoms (4.3 +/- 1.0 to 1.0
      +/- 0.2). The position of the Relief Band was then switched; in the four subjects
      who switched to the placebo position, symptoms worsened (1.0 +/- 0.2 to 4.0 +/-
      1.4); whereas, in the five subjects where the device was switched to the P6
      position, symptoms improved in each subject (3.4 +/- 1.1 to 1.0 +/- 0.7) (p <
      0.01). CONCLUSIONS: Motion sickness symptoms were suppressed by portable
      acustimulation in field studies of seasickness. The Relief Band may be an
      alternative to drug treatments of the nausea and vomiting of seasickness.

PMID- 8747610
TI  - Effects of gas density and ambient pressure on myocardial contractility in the
      rat.
AB  - BACKGROUND: Cardiac contractility and myocardial blood flow have been shown to
      increase when anesthetized and awake rats were exposed to normoxic 0.5 MPa
      ambient pressure, independent of inert gas composition. Similar changes have been
      demonstrated in anesthetized rats breathing a dense (relative density (RD) 5) SF6
      O2 gas mixture at normobaric pressure. HYPOTHESIS: The purpose of the present
      study was to further explore whether cardiac contractility increases during
      hyperbaric exposure as a response to the elevated atmospheric pressure per se or
      rather as a response to increased breathing gas density. METHODS: Arterial
      pressure, left ventricular pressure (LVP), central venous pressure and intra
      esophageal pressure were monitored in anesthetized rats during simulated dives.
      The rats were exposed to various gas mixtures (air, SF6-N2-O2, He-N2-O2), partial
      pressures of O2 (PIO2 0.02 and 0.03 MPa) ambient pressure (PTot 0.1-0.3 MPa) and
      gas density (RD 1-10.1). RESULTS: Cardiac contractility increased briefly by 5
      10% (p < 0.05) during mild hyperoxia (PIO2 0.03 MPa). A concomitant stepwise
      increase in RD (1-10.1) and PTot (0.1-0.3 MPa) by adding SF6 to air, increased
      maximal rate of LVP rise (+dP/dt) and fall (-dP/dt) by 30% (p < 0.01). Two groups
      of rats exposed to either a high density SF6-N2-O2 (RD 5.5) or a normal density
      He-N2-O2 (RD 1.2) breathing gas of identical PTot 0.2 MPa demonstrated similar
      rise in dP/dt (peak 72%, p < 0.05). CONCLUSION: At moderately increased ambient
      pressure, pressure per se increases cardiac contractility independently of the
      breathing gas density.

PMID- 8747611
TI  - Glucose infusion into exercising dogs after confinement: rectal and active muscle
      temperatures.
AB  - BACKGROUND: Intravenous glucose infusion into ambulatory dogs results in
      attenuation of exercise-induced increase of both rectal and thigh muscle
      temperatures. HYPOTHESIS: That glucose (Glu) infusion attenuates excessive
      increase in body temperature from restricted activity during confinement
      deconditioning. METHODS: Rectal (Tre) and quadriceps femoris muscle (Tmu)
      temperatures, metabolic rate, and blood samples were taken before and after 90
      min of moderate treadmill exercise (mean = 3.1 +/- SE 0.2 W.kg-1) at Tdb = 21 +/-
      1 degrees C and 45-60% rh from 7 male mongrel dogs (19.6 +/- SD 3.0 kg) with i.v.
      infusion of 40% Glu in 0.9% NaCl (0.07 ml.kg-1.min-1) or 0.9% NaCl (0.07 mg.g
      1.min-1) both before and after 8 weeks of cage confinement. RESULTS: Mean (+/-
      SE) delta Tre (90-0 min) were: NaCl.after = 1.8 +/- 0.4 degrees C vs. 1.4 +/- 0.3
      degrees C (NS) before confinement; Glu.after = 1.3 +/- 0.2 degrees C vs. 0.9 +/-
      0.3 degrees C (p < 0.02) before confinement. Comparable delta Tmu (90-0 min) data
      were: NaCl.after = 2.5 +/- 0.4 degrees C vs. 1.9 +/- 0.4 degrees C (NS) before;
      Glu.after = 1.6 +/- 0.2 degrees C vs. 1.4 +/- 0.4 degrees C (NS) before. Glucose
      infusion significantly attenuated the rise of Tmu (1.9 degrees vs. 1.4 degrees C)
      only before confinement, but attenuated the rise of Tre both before (1.4 degrees
      vs. 0.9 degrees C) and after (1.8 degrees vs. 1.3 degrees C) confinement. Body
      temperature attenuation was not related to change in plasma volume, osmolality,
      [Glu], [lactate], [cortisol], or heat production with constant VO2. CONCLUSION:
      Intravenous glucose infusion attenuates the rise in exercise core temperature in
      deconditioned dogs by a yet undefined mechanism.

PMID- 8747612
TI  - Diabetes mellitus: rates and outcomes among U.S. Army aviators.
AB  - The U.S. Army Aviation Epidemiology Data Register (AEDR) was queried for Army
      aviators with the finding of glycosuria, hyperglycemia, impaired glucose
      tolerance, diabetes mellitus (DM), use of oral hypoglycemic agents, or use of
      insulin for the period 1988-92. The study tabulated the incidence and age
      specific annual rates of DM, and tabulated the distribution and reasons for
      aeromedical dispositions of aircrew with DM. U.S. Army aeromedical planners can
      expect an incidence of 0.47 cases of DM per 1000 aviator-years per year. Aviators
      over 35 yr old were at the greatest risk. About 78% of the aviators with DM will
      be removed permanently from Army flying duties. This was due primarily to an
      inability to gain dietary control of their condition or the discovery of other
      significant medical conditions, such as coronary artery disease.

PMID- 8747613
TI  - Flying therapy for flying phobia.
AB  - INTRODUCTION: Optimum treatment for aircrew who have developed anxiety associated
      with flight includes a flying phase for desensitization. However, standardized
      flight profiles are not found in the literature. In this study, a method of
      desensitization flying, which may increase the probability of a return to
      productive flying, was devised and assessed. METHOD: Seven aircrew were referred
      for flying desensitization. Behavioral therapy (relaxation training, imaginary
      flying, and thought switching) was usually continued by the Medical Officer
      (Pilot) (MOP). These aircrewmen flew 2-16 sorties in the RAF IAM Hawk or Hunter
      aircraft with the MOP. Each flight was structured with three purposes: to
      approach by increments the flight conditions in each victim's anxiety hierarchy,
      to regulate the amount of low workload, anxiety-vulnerable time during each
      sortie, and to practice relaxation techniques in the air. RESULTS: In all
      referred aircrewmen, anxiety was controllable in flight at IAM. Somatic signs
      diminished and no sortie was terminated early. All returned to operational
      flying. Anxiety recurred in one fast jet pilot while flying solo, and in one
      navigator, both of whom requested a change to transports. A transport pilot had
      recurrent uncontrollable anxiety at high altitude and is grounded. At 9-24 months
      follow-up, 5/7 were flying comfortably with rare, controllable anxiety. We
      conclude that actual exposure to flying is usually necessary for aircrew to
      recover from anxiety associated with flight.

PMID- 8747614
TI  - Variations in the presentation of altitude-induced chokes.
AB  - Altitude-induced decompression sickness (DCS) remains a potential risk for
      individuals involved in flying or altitude chamber activities. The pulmonary form
      of DCS, commonly referred to as chokes, although uncommon, represents the most
      serious manifestation of the disease. This study reports the Davis Hyperbaric
      Laboratory experience with altitude-induced chokes from 1 January 1966 to 31 July
      1994. Age, gender, type and extent of altitude exposure, time of symptom
      development, type of initial symptoms, and response to treatment were reviewed
      for each chokes patient. There were 15 cases of chokes; all were treated with
      compression therapy with complete resolution. Only 2 of the 15 individuals
      presented with the classic triad of substernal chest pain, dyspnea, and cough.
      Substernal chest pain was universally present, and usually occurred very early in
      the course of the disease. The other classic triad symptoms were frequently
      absent. The etiology, pathophysiology, and treatment of chokes are discussed.

PMID- 8747615
TI  - Common accidents among airport ground personnel.
AB  - Work-related accidents at the airport are common, but the incidence and type of
      such events occurring in aviation ground personnel have not been reported
      previously. Information regarding the most common ground accidents at the airport
      is essential in order to implement prevention programs. The purpose of this study
      was to examine the descriptive epidemiology of injury-producing accidents among
      ground personnel at a modern airline. In this study we recorded all reported
      accidents occurring over a 5-year period (1988-92) to workers of a major airline
      in Israel that resulted in 3 d or more of absence from work. During the study
      period 523 work-related accidents occurred in 2000 ground workers. The most
      common accidents were due to slips, trips and falls (n = 211, 40.3%), lifting and
      carrying accidents (n = 107, 20.4%), and machinery accidents (n = 98, 18.7%).
      Work transport accidents and accidents from physical and chemical exposures were
      less common (n = 67, 12.8%, and n = 40, 7.5%, respectively). The accident rate
      decreased from 71 accidents/1,000 worker-years in 1988 to between 40-56
      accidents/1,000 worker-years in the subsequent 4-year period (p = 0.0002). We
      conclude that slips, trips and falls are the most common cause of accidents in
      airport ground personnel. Further studies in other airports are warranted to
      confirm our findings.

PMID- 8747616
TI  - Plethysmography with optoelectronic sensors: comparison with mercury strain gauge
      plethysmography.
AB  - The study and follow-up of certain physiological adaptations in microgravity,
      particularly vascular and venous ones, require the use of reliable equipment that
      yields results well correlated with data provided by equipment usually used in
      clinical examinations. The purpose of the present study was to evaluate the
      reproducibility of results obtained using a new type of plethysmography,
      plethysmography with optoelectronic sensors or volometry, and to verify whether
      these results correlate with those yielded by mercury strain gauge
      plethysmography. The plethysmograph is a device which permits measuring limb
      volume by means of an infra-red light transmitter-receiver system that calculates
      cross-sectional areas at 220 successive points of a given limb segment. Calf
      venous capacity (calf volume measured after 50 mm Hg venous occlusion in the
      thigh) was measured on 27 subjects using volometry and mercury strain gauge
      plethysmography used as reference method. Results showed a good correlation (r =
      0.8, p < 0.001) and a statistically identical reproducibility between the two
      methods even though venous capacity measurements obtained using these two
      techniques were not superimposable because they did not use the same model for
      limb volume measurements. Volometry therefore appears to be a technique of
      interest for the future, to monitor vascular and muscular physiological
      parameters in astronauts during long-term microgravity exposure.

PMID- 8747617
TI  - Convulsive syncope in the aviation environment.
AB  - Syncope in the aviation environment can be a very difficult problem to assess.
      Even more difficult is the differential diagnosis between convulsive syncope and
      epilepsy after the first event. This paper discusses syncope in general and the
      differential diagnosis between vasovagal syncope and other forms of syncope.
      About 50% of all syncopal episodes cannot be identified as to etiology. However,
      a benign outcome for a single syncopal episode, non-cardiac in origin, is the
      norm. The diagnosis of syncope is discussed, emphasizing that a meticulous
      history from an observer or the patient, a good physical examination, and an ECG
      are the cornerstones of diagnosis. Other diagnostic venues are discussed.
      Convulsive syncope occurs in only about 12% of syncopal episodes, 65% of these
      being vasovagal in origin. The other 35% are due to a variety of causes. We found
      no good algorithm to differentiate convulsive syncope from epilepsy. We reviewed
      the literature to develop a differential diagnostic table, focusing on: age,
      awake status, position, emotional/physiologic stressors, onset, aura, appearance,
      injury on falling, seizure characteristics, automatism, length of unconsciousness
      and subsequent confusion, pulse characteristics, blood pressure, urinary
      incontinence, seizure duration, recovery time post-event, post-seizure sequelae,
      amnesia, posture vs. recovery, EEG characteristics, and the value of
      sophisticated diagnostic procedures.

PMID- 8747618
TI  - Of honey bees and aviators: a tale of evolutionary biology.

PMID- 8747619
TI  - Women in combat.

PMID- 8747620
TI  - Some problems of high altitude in the 1930's: a world record attempt.
AB  - During the 1930's, nations competed for aircraft records in height, speed, and
      distance. During 1936 and 1937, attempts on the high altitude record were made by
      a Bristol Type 138 A, built under the sponsorship of the British Air Ministry.
      Designers had to face problems in three main areas: airframe design, engine power
      at extreme altitude, and life support for the pilot. The problems were met by
      developing a lightweight wooden airframe with a double supercharged Pegasus
      engine. A full pressure suit was evolved for the pilot, based on the experience
      of protection of divers in high pressure situations. This was accomplished by
      Professor J.B. Haldane working with Siebe Gorman Ltd. An altitude record of
      49,967 ft was achieved by Sqd. Ldr. F.R.D. Swain on 28th September 1936. This was
      raised to 53,937 ft by Flt. Lt. M.J. Adam on 30th June 1937.

PMID- 8747621
TI  - Cases from the aerospace medicine residents' teaching file. Case #62. Hypoxia.
AB  - Three aviators experience hypoxic symptoms in flight that persist on landing.
      These prove to be the initial presentations of anemia, leukemia and cardiac
      disease.

PMID- 8747622
TI  - Pulse oximetry for preoperative vascular assessment in a thumb near-amputation.
AB  - Pulse oximetry, or photoplethysmography, is widely available in emergency
      departments and intuitively seems well suited to the evaluation of vascular
      compromise in digital trauma. In a review of the medical literature, no cases
      were found in which pulse oximetry was used in preoperative assessment of a
      traumatized digit. We report the case of a patient with a near-amputation of his
      thumb in whom pulse oximetry proved to be a valuable tool in his evaluation and
      treatment because it was a rapid, noninvasive, sensitive means of assessment of
      digital vascular viability. Evaluation and management of this patient is
      discussed, and the pertinent literature concerning the use of pulse oximetry and
      vascular injuries of the hand is reviewed.

PMID- 8747623
TI  - An unusual cause of altered mental status.
AB  - A case of altered mental status secondary to pneumocephalus as a complication of
      sinus surgery is presented. The pathophysiology, clinical presentation,
      diagnosis, and management of pneumocephalus are discussed.

PMID- 8747624
TI  - Anaphylaxis after laboratory rat bite: an occupational hazard.
AB  - Workers exposed to laboratory animals are at risk of developing asthma, rhinitis,
      angioedema, conjunctivitis, and urticaria. Approximately one in five scientists
      and technicians handling small animals will develop laboratory animal allergy
      symptoms within three years of employment, many of whom will have severe symptoms
      requiring a change of occupation. Individuals suffering from allergy to
      environmental allergens, such as pollen and ragweed, are more likely to develop
      allergic reactions to animals, and are more likely to develop asthma. We report a
      case of life-threatening anaphylaxis secondary to a rat bite in a laboratory
      research director with known allergies to rat urinary protein. While rodent bites
      are common in research settings, such severe reactions are extremely rare.

PMID- 8747625
TI  - An unusual presentation of cat scratch encephalitis.
AB  - Cat scratch disease is an infectious illness that has been recognized since the
      1880s; however, our understanding and knowledge of it is still evolving (1). It
      was not until 1991 that the etiologic species, Rochalimaea, was finally confirmed
      (2,3). Only recently have the breadth of its clinical spectrum and the population
      at risk been appreciated. We now realize that signs and symptoms that had been
      considered cardinal for diagnosis may be absent. Cat scratch disease was known to
      afflict primarily children and adolescent; however, the incidence of CSD is
      increasing in immunocompromised groups, such as AIDS and transplant patients
      (3,4). The recent discovery of the infectious agent and improved understanding of
      the disease process have led to new approaches in diagnosis and treatment. We
      present a report of a patient with cat scratch disease who presented with seizure
      and altered mental status secondary to encephalitis.

PMID- 8747626
TI  - Pneumonia in unexpected locations: an occult cause of pediatric abdominal pain.
AB  - Although pneumonia is a known cause of pediatric abdominal pain, it may go
      unrecognized on a patient's initial evaluation. This is particularly true when
      the infection lies outside of the typically described basilar location. We report
      three pediatric patients in whom acute abdominal pain was the sole or primary
      manifestation of a nonbasilar pneumonia.

PMID- 8747627
TI  - Five-year multicenter retrospective review of cyclobenzaprine toxicity.
AB  - Cyclobenzaprine (CBP) has a cyclic structure similar to amitriptyline. In
      overdose, CBP has been suggested to produce the cardiovascular and neurologic
      toxicity found with the cyclic antidepressants. To examine this possibility, a
      retrospective chart review of all cases of CBP exposure reported to five regional
      poison centers was performed for the years 1989-93. There were a total of 750
      charts identified for CBP exposure, of which 523 had data sufficient for
      evaluation. There were 121 polydrug ingestions leaving 402 pure CBP ingestions.
      Ages ranged from 7 mo to 77 yrs, with a mean of 20 yrs; 26% were 6 yrs or less.
      Females comprised 63% of the patient group. No deaths occurred. Dysrhythmias
      beyond sinus tachycardia were infrequent, and none were life-threatening. No
      seizures occurred. Common effects were lethargy, sinus tachycardia, and
      agitation, and both hypertension and hypotension were seen. All symptomatic cases
      with a known time of ingestion were symptomatic within 4 h of ingestion. Doses
      ingested ranged from 5-1000 mg, with a mean of 133 mg. Asymptomatic and
      symptomatic patients had a mean dose ingested of 45 mg and 183 mg, respectively.
      Treatment was primarily gastrointestinal (GI) decontamination and supportive
      care. Other therapies required were mechanical ventilation, dopamine, fluid
      bolus, sedation, and foley catheter. Symptoms requiring treatment beyond GI
      decontamination did not occur with ingestions less than 100 mg. In conclusion,
      cyclobenzaprine does not appear to produce the life-threatening cardiovascular or
      neurologic effects of the cyclic antidepressants in doses less than 1 g. Lethargy
      and anticholinergic effects are prominent, though serious toxicity is infrequent.

PMID- 8747629
TI  - Meperidine: therapeutic use and toxicity.
AB  - Meperidine is a synthetic opioid analgesic frequently prescribed in the emergency
      department. Meperidine is most often administered intramuscularly or
      intravenously, due to its poor oral bioavailability, and is metabolized
      extensively by the liver. Analgesic effects usually last 3-4 hours with
      parenteral administration, and some adverse effects such as nausea may be reduced
      when meperidine is combined with antiemetic or antihistaminic medications.
      Although meperidine is often a preferred analgesic by both patients and
      physicians in the treatment of disorders such as migraine headaches, its
      analgesic efficacy has rarely proven superior to alternative parenteral pain
      medications in controlled trials. In addition, meperidine can precipitate
      monoamine oxidase inhibitor reactions, and during metabolism it is demethylated
      to normeperidine, a compound with significant central nervous system (CNS)
      toxicity. Meperidine should be considered a second line agent in the treatment of
      pain when opioid analgesics are required.

PMID- 8747628
TI  - Subtalar dislocation: evaluation and management in the emergency department.
AB  - Subtalar dislocations are sufficiently uncommon to be unfamiliar but require
      appropriate recognition and management to effect a good outcome. These
      dislocations benefit from urgent reduction that is essential to limiting
      sustained disability. Most can be reduced by closed manipulation at the time of
      presentation. Three cases of subtalar dislocations are presented followed by a
      discussion of the subject.

PMID- 8747630
TI  - A case of traumatic temporomandibular joint dislocation.

PMID- 8747631
TI  - Schizophrenia: Emil Kraepelin, Adolph Meyer, and beyond.
AB  - Prior to 1800, insane persons often lived on the streets or were incarcerated in
      asylums, jails, or prisons. The 19th century witnessed progression in the
      understanding of psychosis, and the hospital management of psychotic patients
      began. While Kraepelin in Europe described the symptoms of what would later be
      called schizophrenia, Meyer developed humanistic treatment for the illness in the
      United States. The early 20th century treatments for schizophrenia included
      insulin coma, metrazol shock, electro-convulsive therapy, and frontal leukotomy.
      Neuroleptic medications were first used in the early 1950s.
      Deinstitutionalization, beginning in the 1960s, resulted in medicated, stable
      schizophrenics being released from state hospitals. However, lack of stable
      living arrangements, misuse of funds, poor medical follow-up, and drug use
      resulted in deterioration of a large segment of this outpatient schizophrenic
      population. The 1990s have seen the development of newer, more effective
      antipsychotic agents and managed care. Both have impacted the state of health of
      schizophrenics in our society.

PMID- 8747632
TI  - Riding Pegasus on a heavenly journey.

PMID- 8747633
TI  - Pulse oximetry for vascular monitoring.

PMID- 8747634
TI  - The use of pulse oximetry in the emergency department.

PMID- 8747635
TI  - The efficacy of routine head computed tomography prior to lumbar puncture in the
      emergency department.

PMID- 8747636
TI  - Low back pain.

PMID- 8747637
TI  - Still listening.

PMID- 8747638
TI  - Rare cause of axillary vein thrombosis.

PMID- 8747639
TI  - Pneumatic rupture of the colon: a sinister consequence of criminal violence.

PMID- 8747640
TI  - Objectives to direct the training of emergency medicine residents on off-service
      rotations: Surgery, part 2.
AB  - This is the 35th article in a continuing series of objectives to direct emergency
      medicine resident experiences on off-service rotations. Vascular and urological
      complaints are common problems in the emergency department and often lead to
      consultation with a surgeon. Because an understanding of the principles of
      surgical diagnosis and treatment is an essential component of the practice of
      emergency medicine, emergency medicine residents rotating on surgical services
      require specific goals and objectives to emphasize early patient assessment,
      identification of the possible need for surgery, and a basic understanding of
      definitive management. Unique aspects of pediatric surgery are also addressed in
      this segment.

PMID- 8747641
TI  - A prospective survey of procedures performed by emergency medicine residents
      during a 36-month residency.
AB  - Future specialty training requirements for emergency medicine may include
      adequately documented records of procedures and resuscitations performed. A
      computer database was developed to track these data and to report the experience
      of one graduating class of nine emergency medicine residents. This study was a
      prospective survey conducted at a community hospital with a fully accredited (PGY
      1-3) emergency medicine residency program. This study showed that data on
      resident procedures can be adequately documented using a computer database to
      determine whether requirements for emergency medicine resident training are met.
      The problems of resident data entry compliance and determining procedural
      competence are discussed briefly.

PMID- 8747643
TI  - Bethann's death.

PMID- 8747642
TI  - Utilization of the emergency department by patients with minor complaints.
AB  - Emergency departments (ED) are frequently utilized by patients with minor
      complaints. It has been a long-standing assumption in the medical community that
      this use was based on the inability of certain subgroups of the population to
      access primary care providers secondary to inability to pay. This study examines
      the use of the ED for minor complaints and the distribution of patients according
      to mode of payment. Our findings suggest that ED utilization for minor complaints
      is not, as previously believed, higher in patients with the inability to pay
      primary care providers. Rather, subsidized patients (Medicare/Medicaid) appear to
      use the ED equally for major and minor complaints, while there is an increased
      utilization by commercially insured patients for minor illnesses and injuries,
      and a lower rate in patients who are self-pay.

PMID- 8747644
TI  - Use of continuous quality improvement to facilitate patient flow through the
      triage and fast-track areas of an emergency department.
AB  - Application of Continuous Quality Improvement techniques can identify (a) major
      causes of delay in evaluation and treatment of ambulatory patients in an
      Emergency Department (ED) and (b) rational solutions to reduce those delays. To
      confirm this hypothesis, a prospective interventional study was conducted at a
      tertiary care teaching hospital with 50,000 emergency visits per year.
      Participants included all patients discharged from the ED in three separate time
      periods. A formal continuous quality improvement process was used to document the
      current process of ambulatory care patient flow and prioritize the causes of
      delay. Solutions were defined and presented to the hospital administration. Two
      solutions were implemented immediately. The effect of these changes was assessed
      by comparing the time interval from presentation to discharge from the ED (length
      of stay) and the time interval from presentation to generation of a chart (chart
      generation). These differences were compared by analysis of variance on
      consecutive patients seen in a 48-hour control period and two postintervention 48
      hour periods. The interventions that were identified and immediately implemented
      were the addition of an admission clerk and the reduction of the Fast-Track nurse
      function to include only patient placement and vital signs. The length of stay
      for all patients was significantly reduced from a mean of 163 +/- 170 min to 115
      +/- 86 and 122 +/- 105 min in two separate postintervention 48-hour samples. The
      mean length of stay for Fast-Track patients not requiring X-ray,
      electrocardiogram, or blood tests was 92 +/- 46 min. After the intervention, this
      was reduced to 73 +/- 46 and 67 +/- 31 min in the same two 48-hour samples. Chart
      generation times were significantly reduced from a mean of 21 +/- 18 min to 8 +/-
      6 min. We conclude that the formal application of Continuous Quality Improvement
      techniques in the Emergency Department can result in appropriate changes in the
      process of patient flow, leading to measurable and significant reductions in
      length of stay for Fast-Track patients.

PMID- 8747645
TI  - Acute mesenteric ischemia in a middle-aged patient: case report and discussion.
AB  - Mesenteric ischemia usually occurs in elderly patients, especially those with
      predisposing factors. It has also been described in young patients using oral
      contraceptive pills or illicit drugs. We present a case of a middle-aged woman
      who developed acute focal ischemia of the small intestine without predisposing
      factors. The unusual presentation of this patient, combined with her relative
      youth, obscured the diagnosis, which was ultimately made at laparotomy. The
      diagnosis of mesenteric ischemia should be considered in patients of any age
      presenting with recurrent or severe abdominal pain, particularly when no
      alternative cause is apparent. The definitive study to diagnose mesenteric
      ischemia is angiography. Unless identified early in its course, the condition may
      progress to frank infarction with a significant increase in morbidity and
      mortality. Because of this, an aggressive approach to the diagnosis and therapy
      of mesenteric ischemia is essential.

PMID- 8747646
TI  - Fast ion-exchange membrane purification of a microsomal protein.

PMID- 8747647
TI  - Use of polylysine in solid-phase protein sequencing.

PMID- 8747648
TI  - Extraction of RNA from gram-positive bacteria.

PMID- 8747649
TI  - Large-scale purification of plasmid DNA for biophysical and molecular biology
      studies.

PMID- 8747650
TI  - Long-term preservation of DNA in agarose gels using 70% ethanol.

PMID- 8747651
TI  - Effects of ethanol concentration and incubation period at 65 degrees C on CAT
      activity in mammalian cell extracts.

PMID- 8747652
TI  - Use of an uninterruptible power supply in a molecular biology laboratory.

PMID- 8747653
TI  - Discriminating PCR artifacts using directed heteroduplex analysis (DHDA).

PMID- 8747654
TI  - Qualitative low-level internal control for nested RT-PCR.

PMID- 8747655
TI  - Ligation- and PCR-based method for sequencing plasmid inserts.

PMID- 8747656
TI  - PCR colony screening using the scintillation proximity assay to detect inserts in
      cloning vectors.

PMID- 8747657
TI  - Automated method to produce bacterial cells at any phase of growth.

PMID- 8747658
TI  - Short technical reports. Quantification of ribozyme-mediated RNA cleavage using
      silver-stained polyacrylamide gels.
AB  - A very sensitive, nonradioactive method for the detection of ribozymes, targets
      for ribozyme cleavage and cleavage products with subsequent densitometric
      quantification of RNA, has been developed. Amounts as low as 15 ng--corresponding
      to 0.16 pmol of a 300-nucleotide RNA molecule--can be visualized in denaturating
      polyacrylamide (PA) gels. This sensitive method allows analysis and
      quantification of ribozyme-mediated cleavage of in vitro-transcribed short
      stretches of RNA. The substitution of N'N'-methylene bisacrylamide by piperazine
      diacrylamide in the PA gels to improve signal-to-noise ratio could not further
      optimize the contrast. Sensitivity was dependent on the presence of urea in the
      gel and could be increased 4-fold in a gel without urea.

PMID- 8747659
TI  - Short technical reports. Effects of lipopolysaccharide on transfection efficiency
      in eukaryotic cells.
AB  - The suitability of different purification methods for preparation of plasmid DNA
      for transfection into eukaryotic cells was systematically investigated. The
      reporter plasmid, pRSVcat, was prepared using several methods, and residual
      impurities in the preparations were quantitated. Transfection with these
      preparations was performed with several cell lines (HeLa, Huh7, COS7 and LMH) and
      two transfection methods: liposome-mediated and calcium phosphate transfection.
      Transfection efficiencies were determined by measuring chloramphenicol
      acetyltransferase expression. Higher transfection efficiencies were obtained with
      plasmid preparations of higher purity (those prepared by anion-exchange
      chromatography or two rounds of CsCl-gradient centrifugation) than with
      preparations of lower purity (those prepared using a silica-based DNA adsorption
      method or a single round of CsCl centrifugation). The results also demonstrated
      specifically that increasing concentrations of lipopolysaccharides in plasmid
      preparations directly correlate with decreasing transfection efficiencies.

PMID- 8747660
TI  - Short technical reports. Modification of the TRI reagent procedure for isolation
      of RNA from polysaccharide- and proteoglycan-rich sources.
AB  - A modification of the TRI Reagent procedure has been elaborated for isolation of
      RNA from polysaccharide- and proteoglycan-rich material. In the modified
      procedure, RNA is precipitated from the aqueous phase by the combined action of
      isopropanol and a high-salt concentration. Under these conditions, RNA is
      effectively precipitated while contaminating polysaccharides and proteoglycans
      remain in the soluble form. The modified precipitation does not prolong or
      increase the complexity of the TRI Reagent procedure. The new procedure was
      tested by isolation of RNA from polysaccharide- and proteoglycan-rich tissues
      such as rat liver and aorta.

PMID- 8747661
TI  - Digital photography for the light microscope: results with a gated, video-rate
      CCD camera and NIH-image software.
AB  - In this report, we describe a relatively inexpensive method for acquiring,
      storing and processing light microscope images that combines the advantages of
      video technology with the powerful medium now termed digital photography. Digital
      photography refers to the recording of images as digital files that are stored,
      manipulated and displayed using a computer. This report details the use of a
      gated video-rate charge-coupled device (CCD) camera and a frame grabber board for
      capturing 256 gray-level digital images from the light microscope. This camera
      gives high-resolution bright-field, phase contrast and differential interference
      contrast (DIC) images but, also, with gated on-chip integration, has the
      capability to record low-light level fluorescent images. The basic components of
      the digital photography system are described, and examples are presented of
      fluorescence and bright-field micrographs. Digital processing of images to remove
      noise, to enhance contrast and to prepare figures for printing is discussed.

PMID- 8747663
TI  - Technical report. Using a world wide web server as a local organizer for protein
      and DNA sequences.
AB  - We have used a local World Wide Web (WWW) server to organize protein and DNA
      sequences that are used frequently in our laboratory. WWW server programs are
      available for most computer platforms and are easily set up with minimal computer
      skills. This approach allows for the easy retrieval of sequence data, which can
      then be used as input for other analysis programs. This format is especially
      simple to use in conjunction with WWW database searches. The sequence files may
      be served to the "public" Internet or kept private by requiring a password for
      access. Other advantages are (i) sequences can be accessed from multiple computer
      platforms using the appropriate WWW-browser; (ii) files can be accessed remotely
      from any computer on the Internet; (iii) only a single sequence format is used,
      simplifying the updating and archiving of data; and (iv) links to remote files
      can also be served in addition to local files.

PMID- 8747662
TI  - Single-step purifications of His6-MutH, His6-MutL and His6-MutS repair proteins
      of escherichia coli K-12.
AB  - The MutS, MutH and MutL proteins mediate methyl-directed-mismatch (MDM) repair in
      Escherichia coli and Salmonella typhimurium. These proteins have been developed
      into powerful tools for screening genomes for polymorphisms and detecting and
      localizing mutations. In an ongoing study of the regulation of MDM repair, we
      developed one-step schemes to purify the E. coli MutS, MutH and MutL proteins
      fused to a polyhistidine (His6) affinity tag. The E. coli K-12 mutS+, mutH+ and
      mutL+ genes were cloned from the Clarke-Carbon plasmid or Kohara-phage library
      into expression vector pET-15b, which allows fusion to the His6 affinity tag.
      Each of the resulting recombinant plasmids complemented the corresponding mutHLS
      mutation in the Cupples-Miller CC106 mutator tester strain, indicating that the
      His6-MutHLS fusion proteins were individually functional in vivo. The His6-MutHLS
      proteins were separately purified by variations of batch binding to Ni(2+)
      chelation affinity resin. The yield of purified His6-MutHLS proteins from these
      procedures was 0.4-0.6 mg from 40 mL of induced culture. The binding properties
      of one-step-purified His6-MutS protein were characterized further. His6-MutS
      exhibited the same mismatch-binding activity and specificity as native MutS in
      side-by-side bandshift assays. These constructs and purification methods should
      be useful to laboratories wishing to apply or develop MutS-mismatch mapping and
      to other applications or studies of the E. coli MutHLS repair proteins.

PMID- 8747664
TI  - Technical report. Optimizing probe selection in directed heteroduplex analysis
      using HDprobe 1.1.
AB  - Directed heteroduplex analysis (DHDA) has proven to be a powerful technique for
      rapid geotyping in human populations. This strategy should also have widespread
      utility in differentiating closely related organisms of medical and public health
      importance through identification of DNA sequence polymorphisms. Identifying an
      optimal probe sequence for use in DHDA has required empirical testing of both the
      positive and negative strands of a number of potential probes. To identify
      optimal probes more efficiently, a computer program has been developed that
      predicts the number of potential stable and unstable mismatches between a probe
      and its target sequences in DHDA. This information can then be used to predict-
      from among a group of potential probes--which one will be the most successful in
      differentiating closely related homologues of a targeted gene sequence. This
      approach was tested on a number of probe and target sequences derived from the
      mitochondrial NADH dehydrogenase subunit 4 gene of the West African black fly,
      Simulium damnosum sensu lato. The number of unstable mismatches predicted to
      occur in a given heteroduplex by the computer program was found to be important
      in differentiating closely related species. Therefore, this strategy is useful in
      identifying informative probes in the development of new DHDA-based assays.

PMID- 8747665
TI  - Protein sequence interpretation using a spreadsheet program.
AB  - Modern spreadsheet programs are inexpensive, easy to use and have a host of
      powerful mathematical and graphical capabilities. Here I show how such programs
      can be used in the interpretation of protein sequences. The methods described
      allow researchers to produce many types of sequence interpretation plots, which
      can then be printed out or conveniently incorporated into documents. It is also
      easy to manipulate the parameters used in sequence interpretation without any
      knowledge of computer programming.

PMID- 8747666
TI  - Efficient, automatic detection of heterozygous bases during large-scale DNA
      sequence screening.
AB  - A crucial factor in the success of positional cloning efforts is the ability to
      screen rapidly many different candidate genes for mutations. By modifying
      standard software, we have improved the detection of heterozygous base positions
      in PCR products sequenced by cycle sequencing. A key element of the method is the
      incorporation of a modified heterozygote detection algorithm that permits the use
      of DNA sequence data derived from PCR and sequencing reactions that have not been
      fully optimized. This allows sequencing runs of average quality to be used. We
      demonstrate that the sensitivity and specificity of the method are well suited to
      mutation detection applications such as positional cloning.

PMID- 8747667
TI  - Oligonucleotide activation of the type IIe restriction enzyme NaeI for digestion
      of refractory sites.
AB  - Certain restriction endonucleases previously shown to exhibit DNA site
      preferences have a two-site DNA cleavage mechanism. These type IIe restriction
      endonucleases include NaeI, NarI, EcoRII, HpaII and SacII. Because of this two
      site mechanism, it is often difficult or impossible to achieve complete digestion
      of DNA substrate. Inasmuch as these enzymes are commonly used in molecular
      biology, a method for enzyme activation to provide complete DNA digestion is
      useful. We have commercialized such a method for NaeI using a double-stranded
      oligonucleotide containing a modified NaeI recognition sequence. Cleavage of
      resistant sites requires the presence of a DNA sequence that is more cleavable to
      bind the activator site. The regions flanking the recognition site on our NaeI
      oligonucleotide cause it to serve as this more cleavable sequence. This activates
      the enzyme to cleave the resistant sequence in the catalytic site, while the
      oligonucleotide modification does not allow the activator to be depleted during
      the reaction. Turbo NaeI provides for rapid digestion of sites previously found
      difficult or impossible to completely cleave and does not interfere with
      subsequent molecular biology techniques that might be performed downstream on the
      substrate DNA, such as ligation, end-labeling or nick translation.

PMID- 8747668
TI  - The influence of the position of surface recording electrodes on the relative
      uptake of the masseteric and temporal M-responses in man.
AB  - The present report aimed at evaluating the influence of recording conditions on
      the relative uptake of direct motor responses obtained in the masseter and
      temporalis muscles after electrical stimulation of their nerves, using a
      monopolar needle technique. In 10 subjects, various surface electromyographic
      recording set-ups were compared using supramaximal M-responses. Volume-conducted
      potentials originating from the masseter muscle could be recorded from the neck.
      For the masseter muscle, the optimal position for the active recording electrode
      was over the anterior and inferior part of the muscle belly. The configuration of
      the masseter M-response recorded from various positions over the muscle belly was
      highly variable both intra- and interindividually. The configuration of the M
      response of the anterior part of the temporalis muscle showed less variability.

PMID- 8747669
TI  - Effects of the antihypertensive drug captopril on human salivary secretion rate
      and composition.
AB  - The effects of the antihypertensive drug captopril on salivary secretion rate and
      composition was evaluated in 24 healthy adults (18-46 yr) according to a double
      blind, cross-over design. Unstimulated and paraffin-chewing stimulated whole
      saliva and 3% citric acid stimulated parotid and submandibular-sublingual (SM-SL)
      secretion were collected at 10.30 a.m. (about 2h after intake of breakfast) on
      day 0 (baseline values), day 1 (experimental acute values) and day 7
      (experimental chronic values) in each treatment period. In 8 of the subjects,
      also morning samples were collected at 7.30 a.m., with the test subjects in a
      fasting condition. Whole saliva was assessed for flow rate and for concentrations
      of sodium, potassium, chloride, calcium and phosphate. In addition, parotid and
      SM-SL secretion were assessed for concentrations of total protein, hexosamine,
      sialic acid, lactoferrin and salivary IgA and for activities of amylase, lysozyme
      and salivary peroxidase. During treatment with the angiotensin converting enzyme
      inhibitor captopril, the secretion rates tended to increase for unstimulated and
      paraffin-chewing stimulated whole saliva and for parotid secretion. For salivary
      composition, no alterations were observed in any of the collected secretions.

PMID- 8747670
TI  - Plaque bacteria counts and vitality during chlorhexidine, meridol and listerine
      mouthrinses.
AB  - The aim of this double-blind study was to enumerate the total number of living
      and dead bacteria on defined tooth areas during the application of antibacterial
      mouthrinses. After prophylaxis, 40 students refrained from all oral hygiene
      measures for 3 d, during which they rinsed with a phenolic compound (Listerine),
      an amine fluoride/stannous fluoride solution (Meridol), 0.2% chlorhexidine (CHX)
      or a control solution (0.02% quinine-hydrochloride). The plaque index (P1I) was
      recorded at the start and the end of the investigation. Total bacterial counts
      (BC) and colony-forming units (CFU) of 1d-, 2d- and 3d-old dentogingival plaque
      were determined. The plating efficiency (PE) was calculated as a percentage of
      CFU/BC and the portion of vital microflora estimated by a vital fluorescence
      technique (VF). All groups started with a P1I approximating 0.1. On day 3, the
      P1I values were 1.21 in the control group and 0.51, 0.37 and 0.14 after
      Listerine, Meridol and CHX use, respectively. A tremendous variation existed
      between the numbers of viable bacteria found per mm2 on the enamel surface and
      day 3 (CHX: 0.2; Meridol: 300; Listerine; 6x10(4); control: 2x10(6)), while
      higher total numbers of bacteria were concomitantly present (CHX and Meridol: 1
      2x10(4); Listerine: 2x10(5); control: 2x10(6)). Both vitality parameters PE and
      VF reached 92% in the control group at day 3, but only 7% after CHX use. With
      Meridol and Listerine, the corresponding PE values were 3% and 43%, respectively,
      while the VF values reached 48% and 54%. The PII, BC, CFU and PE values of the
      CHX and the Meridol groups differed significantly from those of the control
      group. In contrast, Listerine showed no difference as compared to the control
      rinse. Due to the strong antibacterial action of CHX and Meridol during their
      use, almost only dead or non-proliferating bacteria were found on the tooth
      surfaces. Thus, only a thin plaque could develop. As a clinical consequence, both
      substances showed retardation of plaque development as reflected by significantly
      reduced plaque indices.

PMID- 8747671
TI  - pH-cycling of enamel and dentin lesions in the presence of low concentrations of
      fluoride.
AB  - F-dentifrice usage causes slightly elevated fluoride levels in saliva. Therefore,
      the effects of permanent low fluoride concentrations versus daily dentifrice
      treatments were studied on enamel and dentin lesions in a pH-cycling model of
      alternating demineralization and remineralization. Groups received 1) no fluoride
      treatment, 2) 3 mu M (0.06 ppm) F continuously present during re- and
      demineralization or 3) daily 5-min F-dentifrice treatments. Solutions were
      analyzed for changes in calcium and fluoride. Cumulative results (10 d) showed
      that for the non-fluoride group the dentin lesions increased, while for enamel
      lesions mineral uptake and loss were balanced. Addition of 3 mu M F caused small,
      non-significant, enhancement of remineralization (1-7%), while demineralization
      was significantly inhibited for both tissues (9-23%). The daily dentifrice
      treatments resulted in a balance between mineral uptake and loss of dentin, due
      to inhibited demineralization (-33%) and enhanced remineralization (+79%). For
      enamel, the F-dentifrice treatments resulted in 43% reduction of
      demineralization, with no significant effect on remineralization. Fluoride loss
      from the 3 mu M F cycling solutions was significant (up to 50%) and constant
      during the experimental period. Microradiographic analysis showed
      remineralization at the lesion front in enamel. In dentin, the lesion depth was
      increased in all groups, with concomitant mineral deposition in the surface
      region of the dentifrice group. Results indicate that slightly elevated fluoride
      levels may be considerably less effective in inhibiting lesion progression in
      dentin than in enamel, and suggest mineral uptake and loss to occur at similar
      depths for enamel lesions, while demineralization and remineralization occur at
      different depths in dentin.

PMID- 8747672
TI  - The effects of a sodium hypochlorite treatment on demineralized root dentin.
AB  - The effects of a 10% NaOCl treatment for 2 min on demineralized human root dentin
      were investigated by means of: microradiography (MR), scanning electron
      microscopy (SEM), confocal laser scanning microscopy (CLSM) and secondary ion
      mass spectroscopy (SIMS). MR measurements revealed that NaOCl caused a tissue
      contraction not related to water loss but to removal of organic substance(s),
      resulting in reductions of the lesion depth and mineral loss values by 15% and
      42%, respectively. CLSM observations on wet dentin showed that the dentinal
      tubules underneath the surface are clearly observable and not deformed
      substantially by the NaOCl, except near the outermost surface. This indicates the
      importance of wet as well as of dried (high vacuum) observations. SEM micrographs
      (high vacuum) showed definite changes in the outer dentin surface structure; 85%
      of the originally open dentinal tubules were closed after NaOCl treatment. No
      marked changes were observed in the dentin ultrastructure inside lesions, as
      shown by SEM on fractured surfaces. SIMS data, pertaining to samples in high
      vacuum, showed a remarkable increase of chlorine (Cl) content in the entire
      lesion due to the NaOCl, indicating deep penetration of the original OC1 ions.
      The results suggest that the 2-min treatment of demineralized dentin by NaOCl
      solutions removes and/or changes part of the dentin matrix in nearly the whole
      lesion. As a consequence the mineral is somewhat redistributed, the outermost
      surface of a few mu m is changed, but the main dentin structure and element
      composition are still intact. These findings indicate that NaOCl treatments are
      of interest in remineralization and hyper-remineralization studies of dentin.

PMID- 8747673
TI  - Autofluorescence of bulk sound and in vitro demineralized human root dentin.
AB  - The aim of this paper is to report on the demineralization-induced changes in
      dentin autofluorescence. Confocal laser scanning microscopy (CLSM) images and
      fluorescence excitation and emission spectra in vitro demineralized root surfaces
      and sound controls on the same tooth roots were compared. When observed in CLSM
      images, demineralized dentin, excited at 488 nm, gave an increased emission at
      529 nm compared to sound dentin. The difference in fluorescence decreased deeper
      into the root, as the sound dentin underneath the lesion was reached. In
      contrast, when using fluorescence spectrophotometry, excitation around 460 and
      488 nm yielded a lower emission around 520 nm for demineralized dentin than for
      sound dentin, but in a more pronounced peak. From excitation spectra for emission
      around 520 nm, it could be seen that in demineralized dentin the contribution of
      excitation between 480 and 520 nm was more important than in sound dentin. The
      recorded fluorescence in CLSM images was not affected by demineralization-caused
      changes in scattering and absorption properties, due to the small measurement
      volume. Thus, the increased fluorescence for demineralized dentin implies an
      increased quantum yield. In fluorescence spectrophotometry, where the measurement
      volume is large, changes in scattering and absorption do have an influence on the
      fluorescence signal. Then, increased absorption by non-fluorescing chromophores
      and increased re-absorption around the emission wavelength may compensate for the
      increase in quantum yield and absorption around the excitation wavelength by
      fluorophores.

PMID- 8747674
TI  - Effect of titanium on selected oral bacterial species in vitro.
AB  - Titanium granules were tested for their antibacterial effect on strains of
      Streptococcus sanguis, Streptococcus mitis, Actinomyces naeslundii, Haemophilus
      parainfluenzae, Fusobacterium spp. and Prevotella intermedia in comparison with
      amalgam and two of its components, copper and tin. Glass beads were used as
      controls. The number of viable bacteria was estimated in samples exposed to the
      various materials for 1, 3, 6 and 24 h, respectively, and the viable counts were
      related to the baseline value. Titanium showed low antibacterial effect on the
      species tested. Copper and amalgam showed an expressed toxicity to all species
      and differed significantly from titanium and glass particles. Gram positive
      Streptococcus spp. and A. naeslundii showed a lower susceptibility to the metals
      than the Gram negative species. The antibacterial effect of copper and amalgam
      test particles on S. sanguis and P. intermedia was significantly decreased in the
      presence of serum. This study showed that some metals have a toxic effect in
      vitro on oral bacteria, a fact that may play a role in plaque formation when
      these materials are used for dental restorations. Titanium did not have a similar
      antibacterial effect.

PMID- 8747675
TI  - Condensation pressure during amalgam placement in patients.
AB  - The purpose of this study was to investigate the condensation pressure during
      amalgam placement in patients. Forty-four practitioners were asked to fill two
      class 2 cavities in the lower jaw on their patients in their own practice with
      the aid of a force-measuring plugger. This device, with semiconductor strain
      gauges, allowed the dentist to have an identical tactile feedback as with any
      other plugger. Three different amalgams, with different shapes of alloy
      particles, were tested. The results showed a maximum condensation pressure of
      8.9+/-2.4 MPa and 5.5+/-1.8 MPa with a small and a large amalgam plugger,
      respectively. Average condensation pressures were 3.7+/-1.3 MPa for the small and
      2.2+/-0.9 MPa for the large instrument. The total working time required to fill a
      cavity was on average 131 s; the amalgam was effectively condensed for 44 s. No
      significant differences between amalgams with different shapes of alloy
      particles, no influence of time of day, and no difference between female and male
      dentists were found. This study showed that the condensation pressure is lower
      than often recommended, and that it is not statistically different from the
      values obtained in a previous laboratory study.

PMID- 8747676
TI  - Polymerization of composites using pulsed laser.
AB  - The quality of visible-light-cured composites depends on the capability of the
      light source to properly polymerize the material within a specified exposure
      time. In this study, the degree of conversion of different composite materials
      (hybrid and microfilled) of light and dark shades was compared after illumination
      by a standard curing unit and pulsed laser (lambda=468) respectively. The degree
      of conversion was measured by Fourier transform infrared spectroscopy. Results
      obtained by the analysis of the pulsed laser-induced polymerization were
      significantly higher for all the materials and shades observed. All values of the
      degree of conversion were lower for dark shades of all types of composites,
      regardless of the photopolymerization technique used. Besides the surface, better
      polymerization was recorded also at depths of 1.0, 2.0 and 3.0 mm, respectively.
      These values varied from 59.7%+/-2.14 to 84.5%+/-0.33 for pulsed laser (including
      all depths) caused by the saturation effect induced by high power laser pulses
      and from 42.7%+/-1.48 to 74.7%+/-0.99 for standard polymerization.

PMID- 8747677
TI  - Psychophysiological therapy vs. hypnotherapy in the treatment of patients with
      dental phobia.
AB  - The aim of this study was to compare two different modes of behaviorally-oriented
      therapies for dental fear. The subjects were chosen consecutively from the
      waiting-list of a Dental Fears Research and Treatment Clinic. In addition, a
      control group was selected from patients treated under general anesthesia to
      compare levels of dental and general fear with the experimental groups. Twenty
      two women, with a mean age of 31.8 yr, were included and randomly assigned to two
      groups. The median time of avoidance of dental care was 9.5 yr. One group
      received hypnotherapy (HT) and one group a behavioral treatment based on
      psychophysiological principles (PP). Both therapies included eight sessions
      followed by standardized conventional dental test treatments. Pre- and
      posttreatment measures were dental fear, general fear, mood, and patient
      behavior. Nine patients were not able to conclude the treatment sessions (6 HT
      and 3 PP); these patients did not differ significantly from the remaining
      patients before treatment. The PP group reported a statistically significant
      decrease in dental fear as well as a rise in mood during dental situations, as
      opposed to the HT group. General fear levels decreased but not significantly.
      Eleven patients completed conventional dental treatment according to a dentist's
      behavioral rating scale, indicating that they were relaxed, and no problems
      occurred during the treatments. These patients were referred to general
      practitioners within the community dental service. In conclusion, this small size
      study showed that a majority of the patients, who accomplished the behavioral
      therapy and the dental test treatments, became less fearful of dental care and
      were able to manage conventional dental care, including changing dentist.

PMID- 8747678
TI  - Child dental fear: cause-related factors and clinical effects.
AB  - The relationship between child dental fear and clinical effects, and the
      importance of some etiological factors related to the development of dental fear
      in children, were studied in 3,204 urban Swedish children aged 4 to 6 and 9 to 11
      yr. Information concerning child dental fear (as measured by the Dental Subscale
      of Children's Fear Survey Schedule), general fears, parental dental fear,
      parents' employment and native language was obtained through questionnaires. Data
      regarding dental health, behavior management problems (BMP) and modes of dental
      treatment were compiled from dental records. The results showed that child dental
      fear was associated with missing appointments and dental caries. A proportion of
      27% of the children with BMP were dentally fearful, while 61% of the children
      with dental fear reacted with BMP. A model for stepwise regression analysis
      showed that general fears, maternal dental fear, and age were important
      etiological factors in the development of dental fear in children.

PMID- 8747679
TI  - Expression of the alpha-subunit of CR4 (CD11c) by peripheral blood and crevicular
      fluid neutrophils.
AB  - This work determined the levels of expression of CD11c by neutrophils (PMNs)
      collected from subjects with various periodontal conditions. The percentages of
      CD11c-positive crevicular fluid PMNs were significantly lower than those of
      peripheral blood PMNs, but the levels of CD11c expression were similar in PB-PMNs
      and CF-PMNs (P<0.001). On the other hand, no significant difference could be
      found between the groups, either for the percentages of CD11c-positive cells or
      for the CD11c expression levels.

PMID- 8747681
TI  - The thromboelastography and the thromboelastograph technique.

PMID- 8747680
TI  - Plaque surface area after rinsing with a low-level fluoride-containing Darjeeling
      tea.
AB  - Plaque surface area after rinsing with a tea, containing low levels of fluoride,
      was evaluated in 30 human volunteers with a single-blind, one-operator, three
      period, three-treatment cross-over study. The mouthwashes employed were: (1) tea
      (Darjeeling first flush:< 0.2 ppm F-), (2) Meridol(R), (3) control (tap water:<
      0.2 ppm F-). During the experiment the participants refrained from oral hygiene
      procedures and rinsed their mouth three times a day after each meal with 20 ml of
      the respective rinse. After 3 d standardized photographs were taken of the upper
      canines and premolars and the plaque areas were measured planimetrically.
      Statistical analysis showed a marked decrease in plaque surface area after
      rinsing with Meridol, whereas no difference in plaque surface area was observed
      after mouthrinsing with tea and tap water, respectively.

PMID- 8747683
TI  - Thromboelastography: measuring statistical probabilities.

PMID- 8747682
TI  - The normal thromboelastogram and its interpretation.

PMID- 8747684
TI  - Thromboelastography for the assessment of hypercoagulability during general
      surgery.

PMID- 8747685
TI  - Thromboelastography and cardiopulmonary bypass.
AB  - The TEG tracks postoperative hemorrhage after CPB and is useful in guiding
      therapy. Its ability to characterize the overall interaction of all procoagulant
      participants in a final outcome (clot strength) is unique. Much work in the
      future is needed to establish the particular applications for TEG monitoring in
      CPB patients

PMID- 8747686
TI  - Thromboelastography in liver transplantation.

PMID- 8747687
TI  - Thromboelastography and liver transplantation.
AB  - TEG has played an integral part in the growth of liver transplantation. The group
      at the University of Pittsburgh early on realized that coagulation dysfunction
      during liver transplantation would be both severe and dynamic. Each phase of the
      operation appears to have both predictable and unexpected changes in clot
      dynamics. The routine coagulation profile, although of great use, does not
      provide an overview of the interaction of stimulators, inhibitors, and available
      procoagulants to effect a final process, the production of a solid clot. The TEG
      is a unique gross test of clot strength perfectly suited to the changes during
      liver transplantation. The initial pioneering work during liver transplantation
      has inspired the work of others in related surgical fields to explore its
      utility. There is little doubt that its full utility has not yet been realized.
      Many questions still remain with regard to liver transplantation. New medications
      such as aprotinin will be applied to this procedure over the next few years. What
      effect these new medications will have on hemorrhage or thrombosis of vascular
      anastomoses is yet to be adequately explored. A new awareness appears to be
      arriving that normal or excessively hypercoagulable states could contribute to
      such thromboses. TEG as a technology will certainly contribute to a number of
      future studies and clinical care, which will enhance the conduct of liver
      transplantation in the future.

PMID- 8747688
TI  - Application of thromboelastography in other medical and surgical states.

PMID- 8747689
TI  - Thromboelastographic modifications induced by intravenous and subcutaneous
      heparin administration.

PMID- 8747690
TI  - Role of thromboelastography in evaluating other anticoagulant agents: warfarin
      and heparin-dihydroergotamine.

PMID- 8747691
TI  - Thromboelastographic study of fibrinolytic agents.

PMID- 8747692
TI  - The approach of thromboelastography in the monitoring of new synthetic
      antithrombotic agents, GL-522 and GL-2021.

PMID- 8747693
TI  - Comparison of the anticoagulant activities of thrombin inhibitors as assessed by
      thromboelastographic analysis.

PMID- 8747694
TI  - Thromboelastographic analysis of patients receiving aprotinin with comparisons to
      platelet aggregation and other assays.

PMID- 8747695
TI  - Procoagulant and anticoagulant effects of intravascular contrast media as
      assessed by thromboelastography.

PMID- 8747696
TI  - Perspectives on thromboelastography.
AB  - The knowledge of these sources of error together with strict methodology assure
      reliable results and avoid what some authors consider limitations of the test.
      These so-called limitations are actually due to incomplete information or
      insufficient experience. It is our opinion that the key for success when using
      TEG is to use the test in those cases for which it has been indicated. Also, the
      fact that TEG is a global test of coagulation should be kept in mind and
      therefore the need for additional hemostatic tests should be evaluated when
      applicable (Fig.3). According to this review, the established applications of TEG
      are as follows: (1) detection of hypercoagulable states, particularly in the
      postoperative period and for patients with malignancies; (2) management of
      patients who are administered intravenous heparin; (3) monitoring the coagulation
      state during liver transplantation; (4) monitoring the coagulation state and
      management of patients during cardiopulmonary bypass; and (5) diagnosis and
      treatment of hematologic dysfunctions, particularly hemophilia. Management of
      patients under warfarin administration, as well as monitoring of the adjustment
      of subcutaneous heparin prophylaxis in several surgical procedures, should
      probably belong to this list, but further studies are needed to confirm these
      roles. Used by experienced hands, TEG is a valuable hemostatic test, the future
      of which is already present.

PMID- 8747697
TI  - Developmental hemostasis: relevance to hemostatic problems during childhood.
AB  - Congenital and acquired hemostatic disorders present during childhood. An
      accurate diagnosis is critically important in order to implement optimal therapy.
      Over the last century, several investigators have measured plasma concentrations
      of hemostatic components in newborns and compared the results to adult values.
      Clinically significant differences exist for many hemostatic components.
      Recently, three large studies in more than 400 healthy children have provided
      reference ranges for hemostatic components throughout childhood. Together, these
      studies provide insight into the regulation of coagulation and fibrinolysis in
      children in physiologic and pathologic states. Some examples of the influence of
      age on hemostasis are: (1) the diagnosis of some congenital factor deficiencies,
      based on plasma levels, can be difficult due to physiologically low values; (2)
      despite very low levels of many inhibitors of hemostasis, thrombotic
      complications are rare; (3) the interaction of anti-coagulants and thrombolytic
      agents is profoundly influenced by the relative immaturity of hemostasis at
      birth; and (4) in contrast to the risk of thrombosis, healthy infants are at risk
      for vitamin K deficiency bleeding due to poor transport of vitamin K across the
      placenta and plasma concentrations of the vitamin K dependent proteins of less
      than 50% of adults values. The following review discusses the age dependency of
      hemostasis during childhood and the effect of the physiologically immature system
      on the diagnosis and treatment of hemostatic disorders.

PMID- 8747698
TI  - Observations on vitamin K deficiency in the fetus and newborn: has nature made a
      mistake?
AB  - The microsomal mixed function oxidase system metabolizes xenobiotics (Phase I) to
      products that, if not activated and conjugated for excretion (Phase II), are
      capable of forming conjugates with cellular macromolecules, including DNA,
      resulting in toxic, mutagenic, or carcinogenic events. Benzo(a)pyrene (BP), a
      polycyclic aromatic hydrocarbon, is a model carcinogen for this system. Vitamin
      K1 (phylloquinone) is a regulator of BP metabolism. These studies demonstrate
      that K1 is capable of increasing Phase I metabolism and decreasing glutathione
      transferase activity (Phase II) in chick embryo liver; that deprivation of K1
      reduces BP/DNA adducts in mouse liver and reduces tumor formation in mice given
      intraperitoneal BP; and that K1 supplementation increases BP induced tumor
      formation in mice. However, epidemiologic studies indicate that children of
      mothers who smoke during pregnancy may not be at increased risk of cancer. It is
      known that the placentas from these pregnancies exhibit markedly increased levels
      of arylhydrocarbon hydroxylase induced by the polycyclic aromatic hydrocarbons in
      tobacco smoke, but there is no corresponding increase in this enzyme activity in
      the fetus in such pregnancies. We suggest that the low vitamin K level is a
      secondary protective mechanism for xenobiotics, such as BP, that may escape the
      primary placental screen. The recently described role of vitamin K-dependent Gla
      protein as ligands for receptor tyrosine kinases, also establishes K as a link in
      cell growth and transformation. It is proposed that the small total body pool of
      K1 in the adult, which is sufficient only to meet continuing needs, and the even
      smaller pool in the fetus are protective. This protective effect of low K1 levels
      is particularly important in the presence of the high mitotic rates and rapid
      cell turnover in the avian embryo and mammalian fetus.

PMID- 8747699
TI  - Antenatal drugs affecting vitamin K status of the fetus and the newborn.
AB  - Coumarin derivatives and anticonvulsants administered during pregnancy enter the
      fetal circulation, interfering with the action of vitamin K. Vitamin K plays a
      crucial part in the gamma-carboxylation of glutamic acid residues of the vitamin
      K-dependent coagulation factors prothrombin, FVII, FIX, and FX. Other vitamin K
      dependent proteins in the coagulation cascade are protein C and protein S.
      Vitamin K-dependent bone proteins are osteocalcin and gamma-carboxyglutamate
      matrix protein. Administration of coumarol derivatives results in under
      carboxylation of the vitamin K-dependent proteins. Anticoagulation therapy with
      warfarin is followed by an increased risk of embryopathy, which has been shown to
      be greatest between gestational weeks 6 and 12. Administration of warfarin is
      also followed by an increased risk both of fetal intraventricular hemorrhage, and
      of cerebral microbleedings, which may result in microencephaly and mental
      retardation. Treatment with coumarol derivatives should therefore be avoided
      during pregnancy, even in pregnant women with artificial heart valves, and
      replaced by heparin. Hemorrhage in the newborn related to the use of
      anticonvulsant drugs during pregnancy occurs very early within the first 24
      hours, probably due to increased degradation of vitamin K. Transplacental
      administration of vitamin K has been shown to prevent neonatal hemorrhage induced
      by maternal anticonvulsant therapy. Prophylactic administration of vitamin K,
      especially by intramuscular injection, has been reported to be associated with an
      increased risk of childhood cancer. However, subsequent extensive studies have
      yielded no evidence of any relationship between prophylactic vitamin K
      administration and the occurrence of childhood cancer.

PMID- 8747700
TI  - Replacement therapy with a monoclonal antibody purified protein C concentrate in
      newborns with severe congenital protein C deficiency.
AB  - Protein C replacement therapy with a monoclonal antibody purified, virus
      inactivated protein C concentrate was carried out in nine infants (three male,
      six female) with severe congenital protein C deficiency and life-threatening
      purpura fulminans and/or thrombosis associated with disseminated intravascular
      coagulation (DIC). Eight infants were homozygous for protein C deficiency; one
      was a compound heterozygote. The treatment period varied from 22 days to three
      years. The half-life of protein C was found to be as short as two to three hours
      during activation of the coagulation system, increasing to approximately ten
      hours after stabilization. During the acute phase, protein C levels of 0.10 to
      0.25 IU/mL were associated with elevated markers of coagulation activation
      indicating DIC, while protein C levels greater than 0.25 were associated with
      normalization of coagulation markers. No product-related side effects were
      reported. Episodes of bleeding or purpura recurred in all patients who were
      switched to oral anticoagulant therapy, necessitating reinstatement of protein C
      replacement therapy, either as needed to control symptoms, or on a long-term
      prophylactic schedule, alone or in addition to oral anticoagulation. Home
      treatment with protein C concentrate allowed a near-normal life-style for
      patients who otherwise would be hospitalized for long periods of time.

PMID- 8747701
TI  - Factor VIII inhibitors in patients with hemophilia A: epidemiology of inhibitor
      development and induction of immune tolerance for factor VIII.
AB  - Factor (F) VIII inhibitor development remains one of the most serious
      complications in the treatment of hemophilia A. Former and recent studies on
      inhibitor development revealed that patients with severe hemophilia A and
      positive inhibitor family history are at highest risk of developing an inhibitor.
      Comparison of recent inhibitor incidence studies on previously untreated patients
      indicate that the risk of inhibitor development under treatment with recombinant
      FVIII concentrates is comparable to the inhibitor incidence under FVIII
      substitution by plasma-derived concentrates. However, longer observation periods
      are necessary to draw final conclusions. Since inhibitor development may result
      in inefficacy of FVIII concentrates in the treatment of severe bleedings, the
      induction of immune tolerance (IT) is still of main concern. Various regimens to
      induce IT by application of FVIII concentrates have been conducted up to now.
      Success rate appears to be influenced by low to high responder status, number of
      exposure days before onset of treatment, and dosage of therapeutic regimen.
      Especially, discontinuation of IT therapy seems to be associated with failure of
      therapy. Taking into account available data on IT therapy, we recommend early
      onset of a high dosage regimen in high responder patients as soon as possible
      after inhibitor detection, as this is associated with higher success rate and
      shorter elimination time.

PMID- 8747703
TI  - A pediatrician's view: will managed care replace public health?

PMID- 8747702
TI  - Hemostasis in childhood acute lymphoblastic leukemia: coagulopathy induced by
      disease and treatment.
AB  - Thromboembolic events (TE) are serious complications of treatment for childhood
      acute lymphoblastic leukemia (ALL) that result in significant morbidity and
      occasionally mortality. These events are strongly associated with the
      administration of L'asparaginase (ASP). There have been many studies reporting TE
      and assessing the coagulopathy associated with treatment. The intention of these
      studies was to determine a potential mechanism for thrombosis. This article
      reviews the current literature in this area. First, data on thrombotic
      complications in terms of incidence, location, diagnosis, and timing of events
      are summarized. The second section discusses the coagulopathy associated with the
      disease and treatment. To minimize the effects of confounding treatments, the
      data are divided into sections covering pretreatment, after ASP only, after
      combination chemotherapy without ASP, and after combination chemotherapy with
      ASP. In addition, the effects of glucocorticoid steroids on the hemostatic system
      are discussed. As thrombin regulation is critically important to hemostasis, the
      next section of the review discusses the regulation of thrombin in children with
      ALL, both in vitro and in vivo, and the link between impaired thrombin regulation
      and TE in this population. Finally current hypothesis on mechanisms for TE and
      proposed preventative strategies are examined.

PMID- 8747704
TI  - Environmental health during childhood: pediatrician advocacy.

PMID- 8747705
TI  - Commonly asked questions about childhood lead poisoning.

PMID- 8747706
TI  - Children's passive and prenatal exposure to cigarette smoke.

PMID- 8747707
TI  - Incorporating effective smoking prevention and cessation counseling into
      practice.

PMID- 8747708
TI  - Indoor air pollution.

PMID- 8747709
TI  - Child labor.

PMID- 8747710
TI  - Pesticides and children.

PMID- 8747711
TI  - The novel variants of mb-1 and B29 transcripts generated by alternative mRNA
      splicing.
AB  - The Ig-alpha/Ig-beta heterodimers encoded by mb-1 and B29 genes, respectively,
      are crucial for the constitution of the B-cell receptor (BCR). We report here
      novel variants of mb-1 and B29 transcripts produced by alternative mRNA splicing.
      The proteins encoded by these variants are predicted to conserve transmembrane
      and cytoplasmic portions of Ig-alpha and Ig-beta but lack a part of the
      extracellular portions containing cysteine residues which are required for
      intramolecular and intermolecular S-S bonds. Transfection studies revealed that
      the variant mb-1 and B29 did not contribute to the BCR expression on cell
      surfaces. Although peripheral B cells contain small amounts of the variant mb-1
      and B29 transcripts, treatment with an anti-IgM antibody, LPS or IL-4 induces a
      significant increase in amounts of the variant transcripts. These observations
      suggest that B-cell activation induces alternative splicing of mb-1 and B29
      transcripts which encode proteins unable to constitute the BCR.

PMID- 8747712
TI  - Synergistic role of type I interferons in the induction of protective cytotoxic T
      lymphocytes.
AB  - Differentiation of cytolytic T cells can be supported by type I and type II
      interferons (IFN). To characterize the role of type I interferons further we
      tested the role of recombinant IFN-alpha and IFN-beta on the induction of a weak
      immune response, against a low immunogenic tumor, which has been shown to be
      increased by IFN. Both type I interferons IFN-alpha and IFN-beta were able to
      support the differentiation of cytolytic T lymphocytes (CTL). In case of IFN
      alpha no correlation with the antiviral activity could be seen by comparison of
      IFN-alpha1 and IFN-alpha4. The maximal in vitro effects were achieved with very
      low concentrations in the range of 1-100 IU/ml. IFN-alpha showed the strongest
      effects, if added in the early phase of the mixed leukocyte culture, whereas IFN
      beta was most effective when given at the last day the culture. In combination,
      both IFNs gave additional/synergistic effects, whereby addition of IFN-alpha at
      day 0 and IFN-beta at day 4 led to maximal specific CTL responses. In vivo
      augmentation of the anti-tumor immune response by both types of IFNs supported
      the in vitro findings and also the synergistic effect of both types of IFNs could
      be demonstrated. Therefore we propose that IFN-alpha is relevant in the induction
      of CTL responses, i.e., the conversion of precursor T cell into mature cells and
      growth promotion whereby IFN-beta might trigger the lytic machinery of the cells
      and promote differentiation. This synergistic efficacy is also operative in tumor
      rejection.

PMID- 8747713
TI  - Expression of alkaline phosphatase by a B-cell hybridoma and its modulation
      during cell growth and apoptosis.
AB  - The 7TD1 B-cell hybridoma was found to spontaneously express alkaline phosphatase
      (ALP), an enzyme which is produced by splenic B lymphocytes once optimally
      activated. Determination of ALP levels during cell growth and departure to
      apoptosis showed fluctuations. Following a temporary increase within the first 24
      h, enzyme expression was maintained at high levels during the early proliferation
      stage, and then declined from 3 to 4 days in mid-exponential phase to basal
      levels at day 6 when living cells were no longer detectable and the apoptotic
      process was completed. The protein synthesis inhibitor, cycloheximide (1
      microg/ml), decreased ALP production while stimulating a strong apoptosis of 7TD1
      cells, within 4 h. Aphidicolin (1 microg/ml) maintained ALP production and
      provoked a release of ALP activity into the surrounding medium; it also induced
      apoptosis, but with a 24 h delay. Quantification of apoptosis and ALP expression
      by flow cytometry, after simultaneous staining of DNA with Hoechst 33342 and ALP
      with naphthol AS-TR phosphate/Fast Red RC fluorescent reagent, revealed cell
      cycle modulation of ALP expression, its activity increasing as 7TD1 cells
      progressed from G1 phase into S and G2/M phases of the cell cycle in control as
      well as in drug-treated cells. Kinetics of drug-induced apoptosis and higher
      expression of ALP associated preferentially with active cell growth during the
      prevention stage of apoptosis suggested a possible link between cellular ALP
      expression and cell survival.

PMID- 8747714
TI  - Inhibition of smooth muscle cell proliferation in vitro by leflunomide, a new
      immunosuppressant, is antagonized by uridine.
AB  - Chronic rejection in the form of graft vascular disease (GVD) continues to plague
      clinical transplantation of vascularized organs. The histopathology of this
      lesion is characterized by neointimal hyperplasia, smooth muscle cell
      proliferation, and obliterative arteriopathy. Due to the lack of effective
      medical therapy for preventing or reversing these chronic vascular changes,
      retransplantation remains the final resort in treatment. Some of the newer
      immunosuppressive agents, including the new isoxazole derivative leflunomide
      (LFM), have shown efficacy in preventing chronic rejection in animal models of
      transplantation. Although its mechanism of action remains incompletely
      elucidated, previous work using lymphocytes in vitro suggests that the drug might
      act as a tyrosine kinase inhibitor, an inhibitor of de novo pyrimidine
      biosynthesis, or both. In order to elucidate whether the efficacy of LFM in vivo
      is attributable not only to anti-proliferative effects on the recipient immune
      system but also to direct effects on mesenchymal cells in the donor organ, we
      examined the effects of LFM on a transformed 9E11G murine smooth muscle cell (M
      SMC) line in vitro. We demonstrate here that the active metabolite of LFM, A77
      1726, dose-dependently inhibits the constitutive and growth-factor stimulated
      proliferation of M-SMC in vitro. Furthermore, the anti-proliferative effect of
      the drug can be reversed by the addition of uridine to the culture medium. These
      results suggest that inhibition of uridine biosythesis appears to be a mechanism
      by which LFM exerts anti-proliferative effects on both lymphocytes and smooth
      muscle cells, and this dual action may be responsible for its efficacy in
      preventing GVD in vivo.

PMID- 8747715
TI  - Sphingosine, oleylamine and stearylamine inhibit both CD11a/CD18-dependent and 
      independent homotypic aggregation: demonstration by cytofluorimetry.
AB  - An CD11a/CD18-dependent homotypic aggregation pathway is induced by triggering
      CD45 molecules on human thymocytes. By contrast, a CD11a/CD18-independent
      homotypic aggregation process is induced by triggering the CD99 molecule (E2,
      MIC2 gene product) expressed at the surface of either Jurkat T cells or human
      thymocytes. A new quantitative method based on FACS analysis of aggregated cells
      was used and allowed to show that both types of aggregation (CD11a/CD18-dependent
      and CD11a/CD18-independent) were inhibited with sphingosine, oleylamine or
      stearylamine. These three compounds had no effect on the expression of CD99,
      CD45, CD11a, CD18 or other [correction of others] known integrins expressed at
      the surface of the cells studied.

PMID- 8747716
TI  - Calorie restriction modulates lymphocyte subset phenotype and increases apoptosis
      in MRL/lpr mice.
AB  - Defective expression of the Fas apoptotic gene may account for overproduction of
      CD4- CD8- B220+ cells (double-negative) in MRL/MpJ-lpr/lpr (lpr) mice. Previous
      studies have shown that calorie restriction (CR) inhibits the development of
      autoimmune disease and extends life span in these animals. The present studies
      describe the effects of CR on the distribution of lymphocyte phenotypes,
      lymphocyte proliferative response, and cytokine release. The effects of CR on
      dexamethasone (DEX)-induced apoptosis were also studied using propidium iodide
      (PI) uptake and DNA fragmentation in splenocytes and lymph node (LN) cells.
      Weanling female mice were fed a nutritionally adequate semipurified diet either
      ad libitum (AL) or with 40% fewer calories than AL (CR), and killed at 5 months
      of age. CR mice had fewer palpable lymph nodes, and decreased serum anti-dsDNA
      antibodies. Mitogen (ConA, anti-CD3, and LPS) and superantigen (SEB)-induced
      proliferative response was significantly lower in lymphoid cells from AL fed
      animals. FACS analysis of cells from CR animals showed decreased CD4- CD8- cells
      in spleen (1.7-fold, P < 0.025) and LN (1.6-fold P < 0.01) and significantly
      higher CD4+ (spleen, 1.7-fold, P < 0.0001; LN, 2.6-fold, P < 0.025) and CD8+
      (spleen, 1.6-fold, P < 0.001; LN, 5.2-fold, P < 0.005) cells. ConA-stimulated IL
      2 release was increased in CR animals (splenocytes, 7.5-fold, P < 0.001; LN
      cells, 6.1-fold, P < 0.01). Finally, apoptosis in response to Dex was increased
      in CR animals as indicated by the presence of more PI-positive cells (spleen,
      15.8%; LN, 10.7%; P < 0.01) and increased DNA fragmentation. In summary, the
      amelioration of autoimmune disease in MRL/lpr mice by CR is accompanied by
      prevention of the rise in 'double-negative' T cells and by maintenance of
      lymphocyte responsiveness to mitogens and DEX-induced apoptosis at higher levels.

PMID- 8747717
TI  - Kinetics of cytokine production by thymocytes during murine AIDS caused by LP-BM5
      retrovirus infection.
AB  - C57BL 6 mice inoculated with the murine leukemia retrovirus mixture, LP-BM5,
      rapidly produce murine AIDS with many functional similarities to human AIDS.
      Human HIV infection has recently been shown to inhibit thymocyte maturation.
      Therefore, the kinetics of the proliferation of thymocytes induced by Con
      canavalin A (ConA) and levels of cytokines produced by in vitro ConA-stimulated
      thymocytes were examined during the progression of murine AIDS. The proliferation
      of thymocytes induced by ConA was significantly enhanced by retrovirus infection
      at 4 weeks post-infection compared to control, but significantly inhibited during
      8-12 weeks post-infection. Release of IL-2 by ConA-stimulated thymocytes was
      significantly increased by retrovirus infection during 2-5 weeks post-infection
      and 11-18 weeks post-infection compared to control, but significantly decreased
      during 7-9 weeks post-infection. Secretion of IL-4 by ConA-stimulated thymocytes
      was significantly enhanced by retrovirus infection from 5 to 18 weeks post
      infection compared to control. The level of IL-6 produced by ConA-stimulated
      thymocytes was significantly inhibited by retrovirus infection at the beginning
      of retrovirus infection (2-9 weeks), but significantly elevated after 11 weeks
      post-infection compared to control. Release of IFNgamma by ConA-stimulated
      thymocytes, however, was significantly enhanced during the whole period of
      retrovirus infection compared to control, while it surged at 13 weeks post
      infection. We conclude that retrovirus infection affects the thymus, producing
      altered T-cell differentiation via the dysregulation of thymocyte cytokine
      secretion.

PMID- 8747718
TI  - Long-term culture of primary B cells and in vitro expression of an exogenous
      gene.
AB  - Efficient introduction and expression of exogenous genes into primary B cells is
      very important to study B-cell biology and is essential for gene therapy. These
      efforts have often been impeded by the lack of availability of a simple culture
      condition for growth and proliferation of primary B cells as well as the lack of
      vehicles for efficient introduction of genes of interest. In this communication,
      we have developed a culture condition that supports the growth of primary B cells
      from beta-gal-immunized mouse spleen for 30 days without the aid of feeder
      layers. During this period, B cells secreted polyclonal antibodies into the
      medium. To study expression of an exogenous reporter gene, human growth hormone
      (hGH) was introduced into cultured B cells using retroviral vectors. hGH was
      expressed up to 21 days in the absence of drug selection and the infected cells
      continued to secrete immunoglobulins into the medium.

PMID- 8747719
TI  - Immunoregulatory effects of two bone-marrow hexapeptides (myelopeptides) in
      experimental models of immunodeficiency.
AB  - Myelopeptide 1 (MP-1, Phe-Leu-Gly-Phe-Pro-Thr) and myelopeptide 2 (MP-2, Leu-Val
      Val-Tyr-Pro-Trp) are hexapeptides originally isolated from porcine bone-marrow
      cell culture. MP-1 enhanced the number of antibody-forming cells in NZB mouse
      spleen cells in vitro and increased the antibody production in Cy-treated
      (CBAxC57B1/6)F1 mice in vivo. MP-1 increased ConA-induced proliferation of both
      NZB spleen cells in vitro and spleen cells of Cy-treated mice in vivo. MP-1
      restored polyclonal IgG synthesis depressed by PWM in the NZB spleen cell
      culture. MP-2 also evoked immunoregulatory effects which were less pronounced and
      realized at higher concentrations than effects of MP-1. Neither MP-1 nor MP-2
      affected LPS-induced spleen cell proliferation in both NZB- and Cy-treated
      (CBAxC57B1/6)F1 mice.

PMID- 8747720
TI  - Prolongation of the responsiveness of newborn mice to syngeneic IgE by inhibition
      of IgE synthesis.
AB  - Between the ages of 2 to approximately 11 days mice respond to a challenge with
      syngeneic IgE by producing anti-IgE antibodies; by the age of 2 weeks they are
      unresponsive. Even adult mice, however, produce high titers of anti-IgE
      antibodies when immunized with a conjugate of syngeneic IgE and a foreign antigen
      such as keyhole limpet hemocyanin (KLH), indicating that adult tolerance to
      unconjugated IgE resides in the T-cell compartment. The loss of responsiveness in
      2-week-old mice follows closely after the first appearance of IgE-secreting cells
      and detectable serum IgE. This suggests that the delayed onset of tolerance is
      attributable to the delay in synthesis of IgE. Data presented here provide
      support for this hypothesis. A further delay in the initial synthesis of IgE,
      induced by neonatal administration of anti-IgM antibodies, caused a corresponding
      extension of the period after birth during which mice remain responsive to
      unconjugated IgE.

PMID- 8747721
TI  - Abnormal lymphocyte subsets in Kuwaiti patients with type-1 insulin-dependent
      diabetes mellitus and their first-degree relatives.
AB  - Circulating lymphocyte subset imbalance is associated with type-1 insulin
      dependent diabetes mellitus (IDDM). To examine the imbalance in these
      immunoregulatory cells in Kuwaitis with type-1 diabetes and their first-degree
      relatives we analysed T-lymphocyte subsets and HLA-DR expression (activation) in
      18 IDDM patients with a family history of IDDM and 18 non-diabetic first-degree
      relatives of the IDDM patients. Both IDDM patients and their first-degree
      relatives showed a mild lymphopenia. Total T lymphocytes, CD3+ cells, in IDDM
      patients and their first-degree relatives were reduced compared to control
      subjects (P < 0.001). Total B lymphocytes, CD19+ cells, was increased in IDDM
      patients (P = 0.001), but was comparable to controls in IDDM patients' first
      degree relatives. No quantitative abnormality was demonstrated in CD4+ cells in
      IDDM patients; however, these cells were higher in their first-degree relatives
      (P = 0.0089). Suppressor T lymphocytes, CD8+ cells, in first-degree relatives and
      controls were not significantly different; however, these cells were
      significantly reduced in IDDM patients (P = 0.001). The ratio of CD4+/CD8+ cells
      was higher in IDDM patients and their first-degree relatives compared to controls
      (P = 0.0007 and 0.0103, respectively). Activated T lymphocytes, HLA-DR+ CD3+
      cells, were significantly increased in IDDM patients and their first-degree
      relatives. HLA-DR3 was the most common antigen found in IDDM patients (77% vs.
      20% in controls, P = 0.00021). The second most common antigen was HLA-DR4 (55%
      vs. 24% in controls, P = 0.0566). However, no relationship was found in the
      levels of CD3+, CD4+ or CD8+ cells in patients possessing either DR3 or DR4.
      These results suggest that T-lymphocyte subset imbalance not only characterizes
      the cellular autoimmunity in the pathogenesis of IDDM but may also be significant
      in early pre-diabetic stages in those with a family history of IDDM.

PMID- 8747722
TI  - Production and characterization of monoclonal antibodies against human
      natriuretic peptide receptor-A or -B.
AB  - Monoclonal antibodies (mAbs) against human natriuretic peptide receptor-A (NPR-A)
      or NPR-B were produced using NPR-expressing Chinese hamster ovary (CHO) cells and
      soluble chimeric NPRs consisting of the extracellular domain of each receptor
      fused to Fc region of human IgG. Three anti-NPR-A mAbs, designated as A144, A397
      and A416, bound to human NPR-A but not to NPR-B, while an anti-NPR-B mAb B136
      reacted with human NPR-B but not with NPR-A. Competition analysis with the anti
      NPR-A mAbs revealed that two mAbs, A144 and A416, recognize an identical or the
      adjacent site of the receptor and that A397 is directed against another epitope.
      No anti-NPR-A mAb affected binding of atrial natriuretic peptide (ANP) to NPR-A,
      while the anti-NPR-B mAb B136 inhibited binding of C-type natriuretic peptide
      (CNP) to NPR-B. Inhibition of the ligand-binding by B136 is specific in that the
      mAb showed no effect on the binding of ANP to NPR-A. B136 also blocked CNP
      mediated intracellular cGMP accumulation in NPR-B-expressing cells. These results
      suggest that the region recognized by B136 may be related to the ligand-binding
      region of NPR-B. NPR-A- and NPR-B-expressing cells were selectively detected by
      immunostaining using the mAbs. These findings demonstrate that the mAbs will be
      useful to elucidate the role of the natriuretic peptides and their receptors in
      normal and disease states in humans [correction of human].

PMID- 8747723
TI  - P-170 glycoprotein (P-170) is involved in the impairment of natural killer cell
      mediated cytotoxicity in HIV+ patients.
AB  - In the present study we analyze peripheral blood lymphocytes (PBL) from patients
      with human immunodeficiency virus (HIV) infection for both phenotypic expression
      and function of P-glycoprotein (P-170). This transmembrane efflux pump is known
      to be one of the mechanisms responsible for the multidrug resistance (MDR) in
      cancer therapy and it is also constitutively expressed in normal PBL. P-170
      function, evaluated as Rhodamine 123 (Rh123) efflux in flow cytometry, was found
      to be significantly reduced in CD16+ natural killer (NK) cells from patients with
      HIV infection. Interestingly, this reduced efflux significantly correlates with
      the decreased NK cytotoxicity observed in HIV+ patients, as evaluated against the
      NK-specific K562 target cell line. These results support a possible role of the P
      170-related pump in specific immunological lymphocyte function such as NK cell
      mediated cytotoxicity.

PMID- 8747724
TI  - The time course, localization and quantitation of T- and B-cell mitogen-driven
      apoptosis in vivo.
AB  - Apoptosis has very recently been visualized in situ in a mammalian thymus and
      spleen. We report here the first in situ visualization, localization and
      quantitation of the time course of mitogen-altered basal levels of apoptosis
      within the thymus and spleen of a vertebrate. Adult Xenopus leavis, South African
      clawed toads, were injected intraperitoneally with either the T-cell mitogen,
      Concanavalin (Con) A, or the B-cell mitogen, lipopolysaccharide (LPS). Controls,
      reflecting the basal level of apoptosis of both organs, were injected with
      isotonic phosphate-buffered saline for amphibians (APBS). ConA and LPS failed to
      enhance the nearly 2% apoptotic rate in the thymic cortex, which is made up
      largely of immature lymphocytes, but it did double the base level of 2% apoptosis
      in the mature lymphocytes of the medulla, particularly along the corticomedullary
      boundary. In the lymphoid splenic white pulp, the 2% basal level was exceeded
      slightly after ConA treatment, while the 6% basal lymphoid apoptotic rate in the
      red pulp was enhanced 7-fold in 12 h. LPS induced lymphocytic apoptosis in the
      partly erythropoietic red pulp of the spleen after 12 h but did not effect the
      white pulp. Extensive macrophage engulfment of apoptotic cells was apparent in
      both the thymus and the spleen.

PMID- 8747725
TI  - A physiological interaction of T cells and Mac-1+ cells is not necessary to
      induce the selective loss of CD3zeta chains in tumor-bearing state.

PMID- 8747726
TI  - Quality assurance in burn patient care: the James Laing Memorial Essay, 1994.

PMID- 8747727
TI  - Inhibition of neutrophil chemotaxis by plasma of burned patients: effect of blood
      transfusion practice.
AB  - Incubation of normal human neutrophils with plasma from burned patients markedly
      reduced the ability of the cells to respond to a chemotactic stimulus in vitro.
      Previous transfusion of the patients with packed red blood cells did not alter
      the inhibited locomotion of neutrophils, whereas transfusion with normal plasma
      alone attenuated or even abolished the inhibitory activity. The finding provides
      direct evidence for the involvement of circulating suppressive factors in
      neutrophil chemotaxis, rendering burned patients more susceptible to infections.
      In addition, it stresses the relevance of plasma transfusion in clinical
      management and infection control following thermal injury.

PMID- 8747728
TI  - Microbial colonization of large wounds.
AB  - This study determines the nature of microbial wound colonization in 28 patients
      with large burns admitted to the Burn Centre, Haukeland University Hospital,
      Bergen. Altogether, 748 swabs were taken in 141 sampling procedures. A total of
      414 microbial isolates were detected and their resistance patterns to a variety
      of systemic antimicrobial agents determined. The most frequent isolates were
      coagulase-negative staphylococci (21.5 per cent) and Staphylococcus aureus (14
      per cent), followed by Enterococcus species (11.3 per cent), Pseudomonas
      aeruginosa (10.9 per cent) and Candida species (9.7 per cent). Forty-one per cent
      of the enterococci and 36 per cent of the coagulase-negative staphylococci were
      resistant to the aminoglycosides routinely given in conjunction with surgery in
      our ward. Only four of the 89 strains of coagulase-negative staphylococci were
      insensitive to methicillin, and no Staph. aureus were methicillin resistant. The
      time-related changes of burn wound colonization showed that on admission and
      during the first week, staphylococci and alpha-haemolytic streptococci were
      dominant. During the next weeks, these bacteria were gradually superceded by
      enterococci, gram-negative opportunists (mainly Pseud. aeruginosa, Acinetobacter
      calcoaceticus and Escherichia coli) and Candida species. The nature of microbial
      wound colonization and how the flora changes with time should be taken into
      consideration by those treating thermally injured patients.

PMID- 8747729
TI  - Role of gut-derived endotoxaemia and bacterial translocation in rats after
      thermal injury: effects of selective decontamination of the digestive tract.
AB  - This study was performed to investigate: (1) the role of gut-derived
      endotoxin/bacterial translocation in the pathogenesis of sepsis, and (2) the
      possible effects of selective decontamination of the digestive tract (SDD) on
      mortality in rats following 40 per cent full-thickness scald injury. In the SDD
      treated group, Enterobacteriaceae and yeasts were eradicated from the caecal
      mucosa, while the mucosal flora consisting of mainly anaerobes was well
      preserved, within 3 days. The incidence of bacterial translocation to the
      mesenteric lymph nodes (MLN) and viscerae was significantly lowered on postburn
      days 1, 3 and 5 (P < 0.05-0.01). Meanwhile, pretreatment with SDD resulted in
      reductions of the faecal endotoxin levels in different segments of intestinal
      tract to less than 0.5 per cent (0.04-0.45 per cent) of the untreated control;
      there was also a significant attenuation of the elevation of endotoxin
      concentrations in both portal and systemic blood. Intestinal diamine oxidase
      (DAO) activity returned to baseline on day 5 in rats receiving SDD but not in
      controls. The 5-day survival rate in the SDD-treated group was elevated by 26.7
      per cent as compared with controls (P < 0.05). These data suggested that
      endotoxin/bacterial translocation took place early and commonly, which in turn
      contributed to postburn sepsis and mortality. SDD was effective in preventing gut
      origin endotoxaemia and bacterial translocation, and improving the survival rate
      in rats following severe thermal injuries.

PMID- 8747730
TI  - Acute mass burns caused by o-chlorobenzylidene malononitrile (CS) tear gas.
AB  - The use of tear gas in controlling riots has been an accepted practice in many
      countries for the past four decades. In a recent event, a large quantity of tear
      gas canisters were used during a situation of unrest in a Hong Kong Refugees'
      Detention Centre. We report 96 cases of acute burn injury as an unpredicted side
      effect of o-chlorobenzylidene malononitrile (CS) tear gas. There were 47 females
      and 49 males with an age ranging between < 1 to 51 years. These burns were
      categorized as minor burns, with the total body surface area (TBSA) ranging from
      1 to 8 per cent with mean percentage of 3. Most of the patients sustained
      superficial or partial-skin thickness injuries. Only two patients were admitted
      to the Prince of Wales Hospital Burns Centre because of deeper burns; debridement
      and skin grafting was required in one of them. The mechanism of burn injury was
      due to the flame generated from the grenade explosion, direct contact between the
      hot canister and the victim's skin, and the effect of the chemical powder inside
      the canisters when it splashed onto the victim's body. We suggest that the
      noxious transient effects of tear gas are underestimated, furthermore varying
      cutaneous effects and deep burns may result from its uncontrolled use during
      riots. There is a continuing need to reassess the potential toxic effects of CS
      tear gas as a riot control agent and to debate whether its future use can be
      condoned under any circumstances.

PMID- 8747731
TI  - Retrospective evaluation of admission criteria for paediatric electrical
      injuries.
AB  - In the medical community, the practice of admitting all electrical burns for 24
      48 h of observation, monitoring and laboratory evaluation is widespread. This
      retrospective review of paediatric electrical burns was conducted to determine
      which patients may safely be treated as outpatients. Retrospective analysis of
      all paediatric burns admitted between 1980 and 1991 identified 35 patients with
      electrical injuries. Patients were divided into two groups for analysis: those
      burned by exposure to household voltages (120-240 V; n = 26) and those exposed to
      high voltages, in excess of 1000 V (n = 9). The majority of household electrical
      injuries occurred secondary to contact with the household 120 V (21/26). Contact
      with an extremity accounted for the largest number of these injuries (18/26). The
      mouth was the second most frequent site of injury (7/26). Most of these patients
      (20/26) had < 1 per cent BSA burn. No patient in the household-voltage group had
      an arrythmia that required treatment, nor were there any identified examples of
      compartment syndrome or other vascular complications. Seven patients did require
      minimal skin grafting. No deaths occurred in either group. The patients in the
      household-voltage group were significantly younger. High-voltage electrical
      injuries occurred in an older patient population and required more aggressive
      care and surgical intervention. This was evident at the time of initial
      evaluation. Based on these data, healthy children with small partial-thickness
      electrical burns and no initial evidence of cardiac or neurovascular injury do
      not appear to need hospital admission.

PMID- 8747732
TI  - Management of candida septicaemia in a regional burn unit.
AB  - Sepsis due to candida infection is a major cause of mortality and morbidity on
      our unit. Over a period of 3 years and 4 months, 29 cases of candida septicaemia,
      diagnosed by blood cultures, were encountered at the burn unit at Augusta
      Regional Medical Center. Factors known to predispose to fungal sepsis were
      present in all cases. All patients had large burns (14-98 per cent total body
      surface (TBSA) with a mean of 48.3 per cent). All but one patient had at least
      one central venous line. Respiratory problems requiring ventilator support were
      present in 24 patients. Sixteen patients had Candida albicans sepsis, two in
      association with another fungal sepsis. Candida parapsilosis was encountered in
      nine patients, one in combination with another species. Four patients had Candida
      tropicalis. Amphotericin B was prescribed therapeutically in 25 patients, in
      seven together with fluconazole. Two patients received fluconazole only and two
      received no antifungal therapy. There were eight deaths all attributed to sepsis
      and all of whom had multiple organ failure. Five of those who died had completed
      a course of amphotericin B therapy, two were receiving treatment at the time of
      death, and one patient died before culture data became available. Early and
      aggressive therapy is advised and amphotericin B appears to be the drug of
      choice.

PMID- 8747733
TI  - Initial experience of using GRAFTAC absorbable staples to attach split skin
      grafts.
AB  - The GRAFTAC skin stapler with absorbable tacs has been used to attach split-skin
      grafts in 28 patients, under a variety of clinical situations, and the outcomes
      studied. This knowledge has been reviewed in the light of our existing experience
      with the more familiar metal staple. Details of the patients and their conditions
      are presented, with two illustrative case histories, including one where both
      Graftac and metal staples were used. The relative costs were analysed and an
      attempt made to compare the cost-effectiveness of tacs and staples. A rationale
      for use of the more expensive GRAFTAC stapler is presented.

PMID- 8747734
TI  - Epidemiological survey of burns treated in Ankara, Turkey and desirable burn
      prevention strategies.
AB  - From 1 January 1979 to 31 December 1993, 1109 patients were admitted to our burn
      unit located at Hacettepe University. Of the patients, 638 (57.5 per cent) were
      children (under the age of 16 years). The male to female ratio was 1.4:1 in
      children, and was approximately 2.6:1 for patients over 16 years of age. Of the
      638 paediatric patients, 67 (10.5 per cent) sustained electrical burns. The
      causes of injury in the remaining 571 cases (89.5 per cent) were hot liquids in
      379 (66.4 per cent of the non-electrical burns), flame in 190 (33.3 per cent) and
      contact burns in two (0.3 per cent). Of the scalds, 296 (78.1 per cent of the
      scalds), 52 (13.7 per cent), 22 (5.8 per cent) and nine (2.4 per cent) were
      caused by hot water, milk, meal and oil respectively. Of the flame burns, 21
      (11.1 per cent) were due to LPG explosions. Of the 471 adult patients (over 16
      years), 159 (33.8 per cent) were injured by electricity. The causes of non
      electrical burn injuries were: hot liquid in 25, flame in 274, chemical agents in
      four, contact in four, and other causes in four. Although our centre is located
      in Central Anatolia, 41.8 per cent of all patients were referred from the other
      six regions of Turkey. Of the 1109 inpatients, 645 (58.2 per cent) were injured
      in Central Anatolia, 279 (25.2 per cent) in the Black Sea Region, 55 (5.0 per
      cent) in the Mediterranean Region, 18 (1.6 per cent) in the Marmara Region, 34
      (3.1 per cent) in the Aegean Region, 52 (4.7 per cent) in Southeastern Anatolia
      and 26 (2.3 per cent) in Eastern Anatolia. Approximately two-thirds of the
      patients (419) required one or more surgical interventions, including debridement
      and grafting, as well as amputation. The most important early complications were
      acute renal failure (148 patients - 13.3 per cent), sepsis (660 patients - 59.5
      per cent) and gastrointestinal haemorrhage (seven patients - 0.6 per cent). The
      overall mortality rate was 34.4 per cent. The epidemiological pattern of the
      burns showed that emergency measures should be taken to prevent scalding
      accidents to children throughout the country, and for electrical burns in adults,
      particularly those living in the Black Sea Region. In establishing, implementing
      and directing prevention programmes, regional differences should be taken into
      consideration.

PMID- 8747735
TI  - Suicide attempted by burning: a 10-year study of self-immolation deaths.
AB  - In a 10-year retrospective survey of 699 admissions to the Burns Centre of
      Verona, 31 patients (4.4 per cent) had self-inflicted burns. No sex difference
      was found, the mean age was 38 years, with 58 per cent of the patients in the 20
      39-year age group. The mean burned surface area (BSA) was 41 per cent, and 12
      patients (38.7 per cent) died: seven within the first 24 h. The other five
      patients died within 40 days (mean survival: 18 days). A large number of patients
      had a history of previous psychiatric treatment, six patients had previously
      attempted suicide. Four patients were drug addicts, three of whom were affected
      by AIDS and one had been HIV-positive for a long time. The patients had
      continuous psychiatric treatment during the long hospital stay. After discharge
      the patients were assigned to territorial staff for psychiatric treatment. Our
      experience shows that these patients have a higher mortality rate and they need
      constant psychiatric support, which can be useful in preventing further suicide
      attempts.

PMID- 8747736
TI  - A modified method of harvesting split-thickness skin grafts from the abdomen.

PMID- 8747737
TI  - Trends in burn admissions in Scotland during 1970-92.
AB  - This retrospective study involved analysis of the data of the inpatients
      discharged with a diagnosis of burns, from various hospitals in Scotland, during
      the period 1970-92. There were 51,350 such inpatients all over Scotland, with an
      average annual rate of 2233 cases. Overall burn incidence in actual numbers was
      43.7 per cent in < 15 year olds, 41.2 per cent in 15-64 year olds and 15.1 per
      cent in > or = 65 year olds. Burn rates per 100,000 population were highest in <
      15 year olds and lowest in 16-64 year olds. The pattern of burn admissions has
      changed. Since 1987 the highest numbers of burn inpatients were the 16-64 year
      olds, followed by children, then the elderly. There has been a gradual but
      sustained fall in burns admissions in all age categories. The downward trend was
      statistically significant (t = 8.48, 21 d.f., P < 0.001). Though the population
      of the elderly (> or = 65 year olds) increased by about 13 per cent, the burn
      admissions and all deaths due to burns did not reveal an upward trend. The
      population of the old (81+ year olds) increased by 60 per cent during the same
      period. The incidence of burns was above average when > 80 year olds were
      considered separately, approaching the levels found in children. However the rate
      and incidence of burns in the 65-80 year olds resembled that of the younger age
      group (16-64 year olds). The total number of deaths due to burns and/or smoke
      inhalation has declined in all age groups and the decline has been statistically
      significant (chi-squared = 19.62, 1 d.f., P < 0.001). Maximum number of deaths
      occurred in > or = 65 year olds (44 per cent), followed closely by 16-64 year
      olds (43.5 per cent), and 12.5 per cent of deaths in adolescents and children.
      The decline was due to improved management of burns and a decrease in the number
      of patients having large body surface area burns.

PMID- 8747738
TI  - Reflex sympathetic dystrophy of both patellae following burns.
AB  - This study describes a previously undescribed cause of reflex sympathetic
      dystrophy involving both patellae. This syndrome developed following burns
      inflicted over both knees in a male industrial worker. The report highlights
      physical examination findings, investigation results, socioeconomic and
      psychological evaluation, and rehabilitation treatments involved in patients
      suffering from reflex sympathetic dystrophy.

PMID- 8747739
TI  - Caecal perforation in a burn patient.
AB  - A 30-year-old female with a 38 per cent TBSA flame burn developed caecal
      perforation due to non-specific colonic ulceration. Only one such case has so far
      been reported in the literature by Still et al. (Burns 1994; 20: 85). The caecal
      perforation in our patient was treated using a right hemicolectomy. She
      deteriorated postoperatively and died day 21 postburn due to septicaemia, the
      perforation of the caecum contributed to the mortality.

PMID- 8747741
TI  - Recent references.

PMID- 8747740
TI  - Burns of the neuropathic foot following use of therapeutic footbaths.
AB  - Burns affecting the foot in a neuropathic patient may be associated with
      significant functional impairment and prolonged recovery time. Although they
      occur easily, these injuries are rare. We report two patients with deep burns of
      the foot following the use of therapeutic footbaths for pressure ulcers in
      neuropathic patients.

PMID- 8747742
TI  - Standing steadiness measurements: empirical selection of testing protocol and
      outcome measures.
AB  - A variety of methods for measuring the effects of neurotoxic exposure have been
      developed and applied in epidemiologic studies of exposed workers. Although
      impairment of equilibrium is a common complaint among workers exposed to
      neurotoxicants, only a few studies have been published in which quantitative
      measurement of standing steadiness was used to assess occupational neurotoxicity.
      Possible reasons for limited use of these measures include inadequate evaluation
      and validation of testing protocols. The current project was undertaken to
      address some of these issues. Specifically, two studies of normal subjects were
      undertaken a) to compare standing steadiness measurements made with feet together
      or feet apart, and b) to assess the reliability of a number of potential summary
      measures for estimating standing steadiness. Study 1 was performed on eight
      subjects tested on 2 consecutive days. It demonstrated that a) a feet-together
      position resulted in greater systematic variance than a feet-apart position, b)
      sway varied systematically within 60-s trials, c) three 60-s eyes-open/eyes
      closed trial pairs did not appear to provide more information than two pairs of
      trials. In Study 2, 30 subjects were tested on two occasions separated by 2 to 7
      days using the procedure selected on the basis of the results from Study 1.
      Overall, the most reliable of several summary measures of standing steadiness was
      observed to be speed of sway.

PMID- 8747743
TI  - Comparisons of the acute effects of cholinesterase inhibitors using a
      neurobehavioral screening battery in rats.
AB  - The clinical signs of intoxication produced by cholinesterase inhibitors, many of
      which are used as pesticides, are considered important information for regulatory
      purposes. We conducted acute studies of cholinesterase inhibitors to compare
      their effects as determined by a functional observational battery (FOB) and motor
      activity. The acute effects of two carbamates (carbaryl, aldicarb) and five
      organophosphates (OP) (chlorpyrifos, diazinon, parathion, fenthion, and
      diisopropyl fluorophosphate, or DFP) were evaluated on the day of dosing at the
      time of peak effect, at 1 and 3 days, and 1 week after dosing (oral gavage, in
      corn oil). A high dose was selected that produced clear cholinergic signs, and
      lower doses were chosen to produce a range of effects. Generally all
      cholinesterase inhibitors produced autonomic signs of cholinergic overstimulation
      (salivation, lacrimation, and miosis), hypothermia, mild tremors and mouth
      smacking (chewing motions), lowered motor activity, decreased tail-pinch
      response, and altered neuromuscular function (gait changes and increased foot
      splay). The measures generally found to be most sensitive on the day of dosing
      were body temperature, motor activity, gait, and the presence of mouth-smacking
      and fine tremors. However, no single measure was the most sensitive across all
      compounds; for example, the lowest dose of fenthion decreased motor activity by
      86% but did not alter the tail-pinch response, whereas the lowest dose of
      parathion did not lower activity but did decrease the tail-pinch response. For
      some measures, differences in the slopes of the dose-response curves were
      evident. Many effects were still observed at 24 h, but recovery was apparent for
      all compounds. Interestingly, residual effects at 72 h were obtained with the
      carbamates (carbaryl, aldicarb) as well as with the Op fenthion, but not with the
      other compounds. Thus, the overall clinical picture of toxicity was similar for
      these cholinesterase inhibitors, but compound-specific differences emerged in
      terms of the individual measures, dose-response, and time course.

PMID- 8747744
TI  - Prenatal exposure to sodium phenytoin in rats induces complex maze learning
      deficits comparable to those induced by exposure to phenytoin acid at half the
      dose.
AB  - Gravid Sprague-Dawley CD (VAF) rats were administered sodium phenytoin suspended
      in corn oil by gavage once per day on embryonic days 7-18 at a dose of 100 mg/kg.
      Controls were administered corn oil alone by gavage on E7-18. Litters were
      randomly culled to 10. Offspring were regularly weighted, mortality noted, and
      males checked for preputial separation. At approximately 50 days of age offspring
      were evaluated in a straight water-filled channel for swimming proficiency and
      motivation to escape. Following this, rats were tested in the Cincinnati multiple
      T-water maze and scored for errors, latency to find the goal, and presence of
      phenytoin-induced abnormal circling behavior while swimming. Sodium phenytoin
      exposed dams gained weight normally and delivered normally. Offspring mortality
      in the sodium phenytoin group was not increased above controls. No treatment
      effects on preputial separation or offspring growth were observed. No differences
      between groups in swimming proficiency in straight channel performance were
      obtained. In the Cincinnati maze, phenytoin offspring committed significantly
      more errors and had longer latencies to find the goal than controls. Among the
      phenytoin offspring, those exhibiting abnormal circling committed more errors
      than noncircling animals. When compared to previous data using the same maze and
      test protocol, it was found that 100 mg/kg of sodium phenytoin induced
      performance deficits similar to those induced by a dose of 200 mg/kg of phenytoin
      acid. Accordingly, the present data help explain why other investigators have
      reported sodium phenytoin to be more developmentally neurotoxic than phenytoin
      acid. Because the prenatal neurotoxic effects seen with the salt of phenytoin
      occur at lower doses, it suggests that phenytoin is more developmentally
      neurotoxic than previously believed.

PMID- 8747745
TI  - The effects of lead on otoacoustic emissions and auditory evoked potentials in
      monkeys.
AB  - Auditory functioning was assessed in two groups of adult rhesus monkeys (11 years
      of age). One (n = 11) received modest exposure to lead early in life and the
      other (n = 8) served as controls and did not receive any lead supplementation.
      Two lead-exposed monkeys had abnormal distortion product otoacoustic emissions
      (DPEs) and smaller amplitude or absent evoked potentials. These monkeys had
      abnormal distortion product otoacoustic emission (DPEs) and smaller amplitude or
      absent evoked potentials. These monkeys had the highest blood levels recorded in
      their respective groups. For the remaining lead-exposed monkeys there was little
      difference between their DPEs and the DPEs of the control monkeys with one
      exception. DPE amplitudes of the control monkeys increased more rapidly as a
      function of stimulus level than those of the lead-exposed monkeys at most
      frequencies. There was also a significant but modest effect of lead exposure on
      the auditory brain stem evoked responses (ABRs) of these lead-exposed monkeys.
      There was no apparent effect on the middle latency evoked responses (MLRs),
      although that result could be due to the relatively greater variability of the
      MLR.

PMID- 8747746
TI  - Alterations in flash evoked potentials (FEPs) in rats produced by 3,3'
      iminodipropionitrile (IDPN).
AB  - 3,3'-Iminodipropionitrile (IDPN) is a neurotoxicant that produces changes in
      flash evoked potentials (FEPs) 18 weeks after treatment. We examined dose- and
      time-related effects of IDPN on FEPs at earlier time points than previously
      studied (52). Adult male Long-Evans rats were given IDPN (0, 100, 200, 400
      mg/kg/day x 3 days, i.p.) and FEPs were recorded 14 days later. IDPN (400
      mg/kg/day) decreased the amplitudes of some of the "early" and "middle" FEP peaks
      (n30 and N56), and increased the latencies of some early peaks (P21 and P46). A
      separate group of rats was treated with IDPN (0 or 400 mg/kg/day x 3 days, i.p.)
      and FEPs were recorded 1, 3, 7, 14, and 35 days later. The latencies of of all
      portions of FEPs were increased by IDPN, with maximal changes occurring at 7
      and/or 14 days. The amplitude of the middle portions of FEPs (peaks N56, P63,
      N70, P90) were altered as early as day 3, and some changes were observed up to
      day 14. In contrast, the "late" portion of FEPs (peak N160) was affected at later
      times (days 14 and 35). Corneal opacities were noted on days 3 and 7, but were
      largely reversible by day 14. In the time-course study, IDPN decreased colonic
      temperature on days 1, 3, 7, and 14. The present results suggest that IDPN alters
      both the early FEP peaks related to the initial afferent sensory volley, and
      cortical processing associated with the middle and later portions of FEPs.

PMID- 8747747
TI  - Effects of subchronic exposure to toluene on working and reference memory in
      rats.
AB  - Rats that had inhaled 600 ppm of toluene vapor 24 h a day for 50 days after
      weaning at 3 weeks of age were trained in a radial-arm maze with a 4-out-of-8
      baiting procedure, and their performance based upon reference and/or working
      memory was compared with that of air-exposed control animals during the early
      stage of acquisition. Pharmacological challenge testing was also conducted after
      completing a total of 48 training sessions; the effects of scopolamine and
      methylscopolamine on the maze performance were measured after acute i.p.
      administration to determine the long-lasting effects of toluene exposure. During
      the acquisition stage, toluene-exposed rats made a significantly smaller number
      of reference memory errors (entries into "never-baited" arms) and total arm
      entries than the control rats. No significant effects of exposure were observed
      for working memory errors (reentries into "already-entered" arms). During the
      pharmacological challenge testing, only scopolamine increased both types of
      errors significantly. No significant differences due to toluene exposure were
      revealed.

PMID- 8747748
TI  - Drug effects on response-duration differentiation. IV: Effects of trimethyltin.
AB  - Trimethyltin (TMT) is a toxicological agent that produces damage in a number of
      limbic structures, resulting in concomitant disruptions of behavior. The purpose
      of the present study was to determine the utility of response-duration
      differentiation (RDD) responding as a behavioral baseline for studying the
      behavioral consequences of TMT administration. Under the RDD schedule, responses
      of a restricted duration (1-1.3 s) were reinforced, and disruption of this
      performance may represent effects upon fine motor control, timing behavior, or
      both. Two doses of TMT (4 mg/kg) were administered 1 week apart, and behavior
      under the schedule was studied daily for 6 weeks thereafter in a group of four
      rats. Additionally, the effects of diazepam (0.1-3mg/kg) administered prior to
      and following TMT administration were compared. TMT produced disruptions in
      accuracy of responding and increases in rates of responding in the weeks
      following its administration. Behavior had generally recovered by 6 weeks after
      the first TMT administration. Diazepam flattened the relative frequency
      distributions of response durations at lower doses in the TMT-treated rat. These
      data show that RDD responding is sensitive to the effects of TMT, and TMT
      treatment can result in alterations in the effects of diazepam.

PMID- 8747749
TI  - Effects of prenatal maternal ethanol on male offspring progressive-ratio
      performance and response to amphetamine.
AB  - This study was designed to further explore the nature of our previously reported
      reduction in the efficacy of food reinforces for prenatal ethanol-exposed mice.
      We determined the effect of prenatal ethanol exposure on responding for food
      delivered on a progressive-ratio (PR) reinforcement schedule, which has been
      shown to be sensitive to changes in motivation and/or value of reinforcers, and
      we assessed the effects of amphetamine on responding maintained by the PR
      schedule. Subjects were adult (12 months old) male offspring of C57BL/6J mice fed
      liquid diets containing either ethanol (25% ethanol-derived calories, N = 12) or
      sucrose (25% sucrose-derived calories, N = 9) during gestation days 5-17.
      Prenatal ethanol-exposed mice differed from controls by having lower response
      rates and a greater disruption of responding following amphetamine injections.
      The reduced responding for food reward on the PR schedule supports our previously
      advanced hypothesis that prenatal ethanol reduces the efficacy of food
      reinforcers. The enhanced effects of amphetamine found in these adult mice is in
      agreement with previous reports on young rats. Although either of the effects of
      prenatal ethanol exposure observed in the present study are suggestive of altered
      DA systems, current neurochemical studies on either rats or mice provide no
      support for the hypothesis.

PMID- 8747750
TI  - Factors influencing diisopropyl fluorophosphate-induced hypothermia and
      hyperthermia in the rat.
AB  - Exposing rats to the anticholinesterase (anti-ChE) diisopropyl fluorophosphate
      (DFP) causes a transient period of hypothermia followed by a period of
      hyperthermia lasting approximately 48 h. Because a fever is a predominant
      thermoregulatory response in humans exposed to anti-ChE pesticides, the
      hyperthermic response in the rat may be important to understanding the central
      neural mechanisms of anti-ChEs. The purpose of the present study was to assess
      the dependence of DFP-induced thermoregulatory changes on basal behavioral and
      autonomic activity in the rat. Core temperature (Tc), heart rate (HR), and motor
      activity (MA) were monitored via radiotelemetry in unrestrained rats 24 h prior
      to and 72 h after administration of the peanut oil vehicle or 1.5 mg/kg DFP. Mean
      Tc decreased by approximately 4 degrees C by 4 h after DFP, returned to baseline
      by 27 h, and then remained approximately 0.8 degrees C above control daytime
      levels during the second day after DFP injection. Correlations of DFP-induced
      hypothermia and hyperthermia with baseline Tc, HR, and MA were performed. The
      baseline Tc was inversely correlated with the magnitude of DFP-induced
      hyperthermia (r2 = 0.6). DFP-induced hyperthermia was also inversely correlated
      with baseline HR and MA. The minimum core temperature during DFP-induced
      hypothermia was directly correlated with the baseline Tc. The inverse pattern
      between baseline Tc and DFP-induced hyperthermia is similar to that of rats
      administered endotoxin and other pyrogenic agents. Sixty percent of the variation
      in DFP-induced hyperthermia, a toxic response seen > 48 h after exposure, can be
      explained by individual differences in baseline Tc. This relationship may be
      important in understanding the thermoregulatory and metabolic effects of anti-ChE
      agents.

PMID- 8747751
TI  - Neurotoxicity of sodium fluoride in rats.

PMID- 8747752
TI  - The effects of NMDA receptor antagonists and nitric oxide synthase inhibitors on
      opioid tolerance and withdrawal. Medication development issues for opiate
      addiction.
AB  - This article is an exploration of the National Institute on Drug Abuse (NIDA)
      Technical Review on the role of glutamatergic systems in the development of
      opiate addiction. The effects of "glutamate antagonist" medications on opioid
      tolerance and withdrawal are examined. In rodents, mu opioid tolerance can be
      inhibited by noncompetitive N-methyl D-aspartate (NMDA) receptor antagonists
      [MK801, dextromethorphan (DM), ketamine, phencyclidine (PCP)], competitive NMDA
      receptor antagonists (LY274614, NPC17742, LY235959), partial glycine agonists
      (ACPC), glycine antagonists (ACEA-1328), and nitric oxide synthase (NOS)
      inhibitors [L-NNA, L-NMMA, methylene blue (MB)]. Similarly, some of the symptoms
      of opioid withdrawal observed in opioid-dependent rodents also can be inhibited
      by noncompetitive NMDA receptor antagonists (MK801, DM, ketamine), competitive
      NMDA receptor antagonists (LY274614), glycine antagonists (felbamate), and NOS
      inhibitors (L-NNA, L-NMMA, L-NAME, L-NIO, 7-NI, MB). There are some serious
      toxicological effects associated with the administration of some of the
      noncompetitive NMDA receptor antagonists in rodent but not in squirrel monkey
      brain, and some medications induce PCP-like behavioral effects. The medications
      with the most immediate clinical appeal are those that could be coadministered
      with methadone to decrease mu opioid tolerance and dependence; they include DM,
      MB, 7-NI, ACPC, and ACEA-1328.

PMID- 8747753
TI  - The role of the locus coeruleus and N-methyl-D-aspartic acid (NMDA) and AMPA
      receptors in opiate withdrawal.
AB  - Biochemical, behavioral, and electrophysiologic studies indicate that activation
      of the noradrenergic cells in the locus coeruleus (LC) plays an important role in
      the symptoms of opiate withdrawal. Extrinsic factors play a major role in the
      morphine-withdrawal-induced activation of the LC, but intrinsic factors also play
      a role. Among the extrinsic factors, a glutamatergic projection from the nucleus
      paragigantocellularis plays an important role in the withdrawal-induced
      activation of the LC. N-methyl-D-aspartic acid (NMDA) receptors play at most a
      minor role in the withdrawal-induced activation of the LC by glutamate;
      preliminary evidence indicates that alpha-amino-3 hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA) receptors play an important role. Whereas NMDA antagonists
      produce little to no suppression of the activation of the LC during morphine
      withdrawal, they do suppress many morphine withdrawal symptoms. However,
      phencyclidinelike side effects may limit the clinical utility of NMDA
      antagonists. Experiments examining c-fos expression during morphine withdrawal
      indicate that NMDA antagonists may exert some of their influence on morphine
      withdrawal symptoms through actions in the forebrain. Pretreatment with the
      noncompetitive NMDA antagonist MK801 blocks morphine withdrawal-induced increased
      c-fos expression in the amygdala, but not in the nucleus accumbens, frontal
      cortex, or hippocampus. Pretreatment with the competitive NMDA antagonist
      LY274614 (or the alpha2-adrenergic agonist clonidine) blocks morphine withdrawal
      induced increased c-fos expression in the amygdala and nucleus accumbens, but not
      in the frontal cortex or hippocampus. These results help to elucidate some of the
      neuroanatomy and neurophysiology underlying morphine withdrawal. Further, NMDA
      antagonists may not be clinically useful for opiate withdrawal due to their side
      effects, but AMPA antagonists may be of great benefit for alleviating opiate
      withdrawal symptoms in humans.

PMID- 8747754
TI  - Effects of noncompetitive N-methyl-D-aspartate receptor antagonists on opiate
      tolerance and physical dependence.
AB  - Recent research has demonstrated that N-methyl-D-aspartate (NMDA) receptors, a
      class of excitatory amino acid receptors, may have an important role in opiate
      tolerance and physical dependence. Much of the evidence for this has arisen from
      studies that have examined the effects of NMDA receptor antagonists on these
      phenomena. This article summarizes research from our laboratory on the effects of
      NMDA receptor antagonists on opiate tolerance and dependence in rats.
      Noncompetitive NMDA antagonists, including MK-801, ketamine, phencyclidine, and
      dextrorphan have been found at low doses to inhibit the development, or
      acquisition, of opiate tolerance and dependence but not the expression. The
      results suggest that NMDA receptors have a role in the neural plasticity
      responsible for tolerance and dependence. Selected theoretical and therapeutic
      implications of these findings are discussed.

PMID- 8747755
TI  - Perspectives on the N-methyl-D-aspartate/nitric oxide cascade and opioid
      tolerance.
AB  - Opioid tolerance can be modulated by the N-methyl-D-aspartate/nitric oxide
      (NMDA/NO) cascade. Evidence exploring a daily injection paradigm indicates that
      agents antagonizing NMDA receptors can prevent tolerance to morphine and delta
      drugs, but not kappa agents. Drugs work regardless of whether they act as
      competitive or noncompetitive antagonists. Even an agent acting as an antagonist
      on the glycine site of the NMDA receptor is effective. Blockade of nitric oxide
      synthase has similar effects on opioid tolerance, preventing morphine and delta
      tolerance but not that of kappa drugs. Even methylene blue, which can inhibit
      guanylyl cyclase activity, is effective, presumably by blocking cGMP formation
      resulting from NO release. These results demonstrate the importance of an intact
      NMDA/NO cascade in the production of opioid tolerance and open new possibilities
      in the design of agents acting on opioid tolerance.

PMID- 8747756
TI  - Nitric oxide synthase inhibitors. Preclinical studies of potential use for
      treatment of opioid withdrawal.
AB  - Four inhibitors of nitric oxide synthase (NOS), administered as acute
      pretreatments, attenuated several signs of naloxone-precipitated opioid
      withdrawal in morphine-dependent rats. Profiles of these drugs for inhibiting the
      expression of withdrawal were similar to that of clonidine, a drug used
      clinically to treat opioid withdrawal. The nonselective NOS inhibitors, NG-nitro
      L-arginine and NG-nitro-L-arginine methyl ester, and N(5)-(1-iminoethyl)-L
      ornithine, a selective inhibitor of endothelial NOS, Increased blood pressure in
      awake, morphine-naive and morphine-dependent rats not undergoing withdrawal. 7
      Nitroindazole, a selective inhibitor of neuronal NOS, did not elevate blood
      pressure. Insofar as hypertension is a component of opioid withdrawal in humans,
      the ability of 7-nitroindazole to attenuate morphine withdrawal in rats without
      eliciting a vasopressor response suggests that 7-nitroindazole may have human
      therapeutic potential. Research directions for the continued development of 7
      nitroindazole as a therapeutic modality are discussed with respect to issues of
      physical dependence, tolerance, and safety.

PMID- 8747757
TI  - The severity of naloxone-precipitated opiate withdrawal is attenuated by
      felbamate, a possible glycine antagonist.
AB  - Recent studies indicate that an N-methyl-D-aspartate (NMDA) receptor system in
      the rostral medulla is involved in opiate withdrawal. Although NMDA antagonists
      attenuate naloxone-precipitated opiate withdrawal, they can cause phencyclidine
      (PCP)like effects that contraindicate clinical use. Because NMDA channels contain
      sites for the glutamate coagonist, glycine, we assessed the effects of
      glycinergic agents on naloxone-precipitated opiate withdrawal in rats. The
      putative antagonist, felbamate (100, 300 mg/kg), attenuated overall withdrawal
      severity in a dose-related manner and reduced occurrences of chews, teeth
      chatters, and penile grooming. The partial agonist, D-cycloserine (3, 10 mg/kg),
      attenuated withdrawal severity, but not in a dose-related manner. Conversely, the
      low dose of the partial agonist, (+/-)-HA-966 (3, 10 mg/kg), heightened the
      occurrences of some withdrawal signs. These results support a role for glycine in
      opiate withdrawal and suggest that these agents, which do not cause PCPlike
      effects, may be potential treatment for agents for opiate detoxification.

PMID- 8747758
TI  - NMDA antagonists as neurotherapeutic drugs, psychotogens, neurotoxins, and
      research tools for studying schizophrenia.
AB  - Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate (Glu)
      receptor have become the focus of considerable attention as potential
      neurotherapeutic agents in view of mounting evidence implicating NMDA receptors
      in acute central nervous system (CNS) injury syndromes such as stroke, trauma,
      and status epilepticus. In addition, NMDA receptor antagonists are of potential
      interest for the clinical management of neuropathic pain and preventing the
      development of tolerance to opiate analgesics. A potentially serious obstacle to
      the development of NMDA antagonists as neurotherapeutic drugs is the paradoxical
      fact that whereas these agents do have significant neurotherapeutic potential,
      they also have psychotogenic and neurotoxic properties. We have been intensively
      investigating the mechanisms underlying these adverse properties and have
      discovered several methods of suppressing or preventing their expression. In
      addition, we have been exploring the possibility that a common mechanism may
      underlie the psychotogenic and neurotoxic actions of these agents and that this
      mechanism may have relevance to the pathogenesis of idiopathic psychotic
      processes such as schizophrenia. In this chapter, we will review our findings
      pertaining to NMDA antagonists in the dual context of their value as tools for
      exploring mechanisms underlying neuropsychiatric disturbances, particularly
      schizophrenia, and their potential promise as therapeutic agents. For additional
      references and a more complete elaboration of our hypothesis pertaining to NMDA
      receptor dysfunction and schizophrenia, please see a recent review (Olney and
      Farber 1995).

PMID- 8747759
TI  - N-methyl-D-aspartate (NMDA) receptors, mu and kappa opioid tolerance, and
      perspectives on new analgesic drug development.
AB  - This laboratory perspective reviews the pharmagologic approaches that have been
      used in preclinical animal models to demonstrate the ability of competitive
      (LY274614) and noncompetitive (MK801 and dextromethorphan) N-methyl-D-aspartate
      (NMDA) receptor antagonists to attenuate or reverse the development of morphine
      tolerance. We provide additional data to support previous observations that these
      NMDA antagonists modulate morphine (mu) opioid tolerance but do not affect
      U50488H (kappa 1) opioid tolerance. A strategy, which utilizes efficacy as an
      NMDA receptor antagonist and clinical safety, provides the basis for a discussion
      of the clinical potential of dextromethorphan, ketamine, and felbamate as
      modulators of opioid tolerance in pain patients or opioid addicts. The potential
      use of NMDA receptor antagonists and nitric oxide synthase (NOS) inhibitors in
      neuropathic pain is also discussed.

PMID- 8747760
TI  - Correlation between the exercise-induced increase in left ventricular filling
      pressure and the extent of ischemic or infarcted myocardium.
AB  - We investigated the correlation between left ventricular filling pressure and the
      extent of ischemic or infarcted myocardium in 39 patients with coronary artery
      disease: 25 with angina pectoris (group A) and 14 with old myocardial infarction
      but without overt transient myocardial ischemia (group B). Hemodynamic parameters
      were measured at rest and during exercise. The extent and severity scores of
      ischemia or infarct were calculated using thallium-201 (201Tl) myocardial single
      photon emission computed tomography. In group A, the extent and severity scores
      of ischemia were strongly correlated with pulmonary artery wedge pressure at peak
      exercise (r = 0.71, p < 0.001, r = 0.62, p < 0.01, respectively). In group B, the
      extent and severity scores of the infarct were significantly correlated with left
      ventricular ejection fraction (r = -0.81, p < 0.001, r = -0.77, p < 0.01,
      respectively), but were not correlated with pulmonary artery wedge pressure.
      Since no relationship was found between the extent of infarct and left
      ventricular filling pressure, dynamic exercise appears to elicit a different
      compensatory mechanisms in nonischemic myocardium for exercise-induced transient
      ischemia and in noninfarcted myocardium for old infarction. The compensatory
      mechanism in patients with old myocardial infarction may be affected by
      ventricular remodeling.

PMID- 8747761
TI  - Augmented secretion of atrial and brain natriuretic peptides during dynamic
      exercise in patients with old myocardial infarction.
AB  - To assess the role of atrial and brain natriuretic peptides (ANP, BNP) in
      maintaining cardiac performance at rest and during exercise in patients with
      cardiac dysfunction, we measured plasma levels of ANP and BNP during 201Tl
      dynamic exercise testing in 32 patients with angiographically proven old
      myocardial infarction (OMI) and 35 normal control subjects (CS). Plasma levels of
      ANP and BNP at rest were significantly higher in patients with OMI than in CS
      (ANP, 42.6 +/- 19.3 vs 19.4 +/- 2.4 pg/ml, p < 0.01; BNP, 53.4 +/- 32.5 vs 2.8 +/
      0.8 pg/ml, p < 0.01, respectively). Correlations were found between plasma
      levels of these peptides and left ventricular ejection fraction (LVEF), cardiac
      index (CI), pulmonary capillary wedge pressure (PCWP) and left ventricular end
      diastolic pressure (LVEDP) in patients with OMI. In addition, a strong positive
      correlation was found between plasma levels of these peptides and the severity
      score obtained from 201TI myocardial scintigraphy. During exercise, both ANP and
      BNP significantly increased in patients with OMI. However, in CS, although ANP
      increased, BNP remained unchanged. The changes in plasma levels of ANP or BNP
      from at rest to peak exercise correlated with LVEF, CI, PCWP, LVEDP and the
      severity score in patients with OMI. These findings indicate that ANP and BNP
      play an important role in maintaining cardiac performance at rest and during
      exercise in patients with cardiac dysfunction.

PMID- 8747762
TI  - Exercise-induced ST-segment elevation--role of left ventricular wall motion
      abnormalities and coronary artery narrowing.
AB  - We studied the causes of exercise-induced ST-segment elevation. Group I consisted
      of 15 patients with anterior myocardial infarction in the absence of a coronary
      artery luminal narrowing of 75% or more. Group II consisted of 36 patients with
      predominantly exertional angina and a luminal narrowing of 90% or more in the
      left anterior descending coronary artery in the absence of previous myocardial
      infarction. In group I, exercise-induced ST-segment elevation occurred frequently
      during treadmill exercise (15/15, 100%). None of the patients showed 201Tl
      redistribution. The standard deviation of the phase in radionuclide
      ventriculography increased during bicycle exercise. Of group II patients, only
      those with 99% narrowing and poor collaterals showed exercise-induced ST-segment
      elevation (13/14, 93%), whereas none of those with complete occlusion or 99%
      narrowing and good collaterals, or 90% narrowing showed ST-segment elevation. In
      group II, patients with exercise-induced ST-segment elevation showed lower 201Tl
      uptake during exercise and washout in the territory of the diseased vessel than
      those without exercise-induced ST-segment elevation. In conclusion, wall motion
      abnormalities may cause exercise-induced ST-segment elevation independently of
      myocardial ischemia. In patients with predominantly exertional angina, exercise
      induced ST-segment elevation may be a marker for 99% narrowing with poor
      collaterals and severe myocardial ischemia.

PMID- 8747763
TI  - Effective and safe dose of intracoronary nicorandil in man.
AB  - Nicorandil is a hybrid of a nitrate and a potassium channel opener, and has a
      potent vasodilatory effect on coronary arteries. The effects of intracoronary
      injection of nicorandil on coronary circulation were examined in 12 adult
      patients with angiographically normal or near-normal left coronary arteries to
      determine the optimal dose of this agent. The intracoronary injection of
      nicorandil (up to 1 mg over 1 min) dilated left coronary artery segments in a
      dose-dependent manner, with no significant effects on systemic hemodynamic
      parameters. The percent increase in the epicardial coronary artery diameter with
      1 mg nicorandil (31 +/- 5%, mean +/- SEM) was not significantly different from
      that with 0.3 mg sublingual nitroglycerin (39 +/- 5%). Coronary sinus venous
      oxygen saturation increased immediately after the intracoronary injection of 1 mg
      nicorandil, and then returned to the baseline level within 3 min. Neither
      arrhythmias nor conduction disturbances were observed. These results indicate
      that dilatation of the epicardial coronary artery was achieved with intracoronary
      nicorandil in a dose-dependent manner (up to 1 mg over 1 min) without any adverse
      effects in man, and the dilatory effect on coronary resistance vessels was of
      short duration.

PMID- 8747764
TI  - Prognostic determinants of hypertrophic cardiomyopathy--the results of the Shiga
      Cardiomyopathy Study.
AB  - Previous studies have reported that patients with hypertrophic cardiomyopathy
      (HCM) are prone to sudden death. In this study, we retrospectively assessed the
      prognosis and any influencing factors in 83 patients (66 male, 17 female) with
      HCM. Twenty-two patients were obstructive, 40 were non-obstructive, 18 were
      apical HCM and 3 were unclassified. Four of the 83 cases progressed to left
      ventricular dilatation and dysfunction during the follow-up period. The mean age
      was 51.2 years (range 16 to 73) and the mean duration of follow-up was 6.7 years
      (range 0.3 to 15.1). The 5- and 10-year survival rates were 98% and 89%,
      respectively. Five patients dies; 3 from cardiac events (two sudden deaths and
      one due to congestive heart failure) and 2 from malignant diseases. The lack of a
      family history of sudden death and the amplitude of the S wave in lead V1 (less
      than 2.0 mV) were associated with a favorable prognosis. None of the patients who
      were diagnosed before age 50 died, but this observation was not statistically
      significant. None of the patients with apical HCM died, but the classification of
      HCM was not significantly associated with the prognosis. None of the patients
      without medication died and medical treatment did not influence the prognosis.
      Sex, family history of HCM, the patient's symptoms and physical signs, NYHA
      classification of cardiovascular disability, thickness of the septum and the
      posterior wall of the left ventricle, dimension of the left atrium, and the left
      and right ventricles in echocardiogram, amplitude of the R wave in lead V5, the
      depth of the negative T wave and atrial fibrillation did not influence the
      prognosis.

PMID- 8747765
TI  - Angiotensin II type-1 receptor antagonist as well as angiotensin converying
      enzyme inhibitor attenuates the development of heart failure in aortocaval
      fistula rats.
AB  - OBJECTIVES: We investigated the effect of chronic administration of an
      angiotensin II type-1 receptor antagonist in the development of heart failure due
      to volume overload in rats. METHODS: Aortocaval fistula (AVF), a model of volume
      overloaded heart failure, was induced in rats by our newly developed technique
      using a simple and rapid 18-gauge needle multipuncture. After 3 weeks of oral
      administration of an angiotensin II receptor antagonist TCV-116, 1 mg/kg per day,
      we evaluated the hemodynamics, heart weight, and degree of left ventricular
      dilatation. We also compared the effect of TCV-116 with that of an angiotensin
      converting enzyme inhibitor delapril, 1 g/L in drinking water. RESULTS: AVF heart
      failure produced by our technique exhibited significant increases in the left
      ventricular end-diastolic pressure (LVEDP) (12 = 1 vs 4 +/- 1 mmHg, p < 0.05),
      right atrial pressure (RAP) (5.0 +/- 0.6 vs 1.0 +/- 0.4 mmHg, p < 0.05), right
      ventricular systolic pressure (RVSP) (58 +/- 6 vs 33 +/- 1 mmHg, p < 0.05), left
      ventricular weight (LVW) (3.00 +/- 0.13 vs 2.09 +/- 0.04 g/kg BW, p < 0.05),
      right ventricular weight (RVW) (0.93 +/- 0.05 vs 0.59 +/- 0.01 g/kg BW, p <
      0.05), and left ventricular end-diastolic volume index (LVEDVI) (2.55 +/- 0.14 vs
      0.80 +/- 0.12 ml/kg BW, p < 0.05) as compared with these values in sham-operated
      rats. There were no differences in shunt ratio between untreated and TCV-116- and
      delapril-treated AVF groups. TCV-116 improved these hemodynamics, as did delapril
      (TCV-116 vs delapril: LVEDP 8 +/- 1 vs 8 +/- 1, RAP: 3.8 +/- 0.6 vs 2.3 +/- 1.4,
      RASP: 50 +/- 2 vs 46 +/- 3, LVW: 2.53 +/- 0.11 vs 2.52 +/- 0.15, RVW: 0.80 +/-
      0.04 vs 0.77 +/- 0.06, LVEDVI: 1.67 +/- 0.15 vs 1.70 +/- 0.17). CONCLUSION: These
      results suggest that AVF rats with volume overload produced by a new
      multipuncture method exhibit both right- and left-side heart failure. Angiotensin
      II type-1 receptor antagonist as well as angiotensin converting enzyme inhibitor
      attenuate the development of this type of heart failure in rats.

PMID- 8747766
TI  - The effect of left ventricular chamber compliance on early diastolic filling
      during coronary reperfusion.
AB  - This study was designed to assess the changes in left ventricular (LV) diastolic
      filling and to evaluate the dynamic determinants of LV diastolic filling during
      coronary reperfusion after acute myocardial ischemia. We examined LV diastolic
      pressure-volume relations (D-PVRs) using the conductance catheter technique with
      a high-fidelity micromanometer, and the transmitral flow using transesophageal
      pulsed Doppler echocardiography in 9 open-chest anesthetized dogs with the
      pericardium opened. We measured early diastolic peak flow velocity (E), late
      diastolic peak flow velocity (A), the ratio of peak E to peak A (E/A),
      operational chamber compliance at the minimum LV pressure [(dV/VdP) nadir], and
      the time constant of LV relaxation (TC). Acute regional myocardial ischemia was
      produced by occluding the proximal portion of the left anterior descending
      coronary artery. Data were acquired at baseline, 10 min after acute myocardial
      ischemia, and after 15 and 90 min of reperfusion under left atrial pacing at 100
      beats/min. During myocardial ischemia, D-PVRs shifted upward and rightward on the
      same curvilinear relationship compared with that at baseline (LV end-diastolic
      pressure (LVEDP) from 7.3 to 10.5 mmHg, LVEDV from 25 to 31 ml, both p < 0.01),
      accompanied by a decrease in peak E and E/A (E from 41 to 25 cm/sec, E/A from 1.7
      to 1.1, both p < 0.01) and a prolongation of TC (from 25.4 to 30.3 msec, p <
      0.01). After coronary reperfusion, D-PVRs returned to baseline accompanied by an
      improvement in the peak E and E/A ratio. No significant changes in peak A were
      observed in any of the stages. There was no correlation between peak E and TC,
      however, a significant positive correlation was observed between peak E and
      (dV/VdP) nadir (r = 0.76, p < 0.01). In conclusion, this study demonstrated that,
      using pulsed Doppler echocardiography, the improvement of diastolic filling after
      coronary reperfusion was based mainly on changes in early diastolic filling, and
      that LV operational chamber compliance at early diastole, rather than a LV
      relaxation property, might play an important role in determining early diastolic
      filling during coronary reperfusion.

PMID- 8747767
TI  - Infection in the organ transplant recipient. An overview.
AB  - Considerable progress has been made in elucidating the factors involved in the
      pathogenesis of infection in the organ transplant patient. One of the general
      principles that has emerged is that the risk of clinical infection, particularly
      opportunistic infection, is determined largely by the interaction between the
      patient's net state of immunosuppression and the epidemiologic exposures the
      patient encounters. The two major factors that determine the net state of
      immunosuppression are the nature of the exogenous immunosuppressive therapy that
      is administered and whether or not infection is present with one or more of the
      immunomodulating viruses (particularly cytomegalovirus, Epstein-Barr virus, and
      the hepatitis viruses). Finally, the therapeutic prescription for the transplant
      patient has two components--an immunosuppressive component to prevent and treat
      rejection and an antimicrobial component, which is linked to the intensity of the
      immunosuppressive therapy required, to make this safe. This reflects the
      recognition that the two major barriers to successful transplantation, rejection
      and infection, are closely tied together by the current requirement for lifelong
      immunosuppressive therapy. Progress in one area will have beneficial effects on
      the other.

PMID- 8747768
TI  - Infection in the bone marrow transplant recipient.
AB  - Bone marrow transplantation (BMT) is widely used in the treatment of
      myelodysplastic disorders and leukemia. Despite improvements in patient
      management, infection as a consequence of the immunodeficiency states that follow
      BMT remains a significant cause of morbidity and mortality. This article provides
      an overview of the major infections after BMT with an emphasis on new
      developments in diagnosis, treatment, and prophylaxes that have occurred in
      recent years.

PMID- 8747769
TI  - Prevention of bacterial infection in the transplant recipient. The role of
      selective bowel decontamination.
AB  - Bacterial infections during the first month after liver transplantation remain a
      serious problem despite perioperative administration of systemic broad-spectrum
      antibiotics. These infections usually have been caused by aerobic gram-negative
      bacilli from the alimentary tract, and the most promising approach during the
      past decade is to eliminate or suppress these organisms by SBD. Several centers
      that have used SBD for prophylaxis have reported favorable results, but only one
      of the studies has been prospective and randomized. Based on the limited
      information now available, it seems that the efficacy of SBD is dependent on
      eliminating or suppressing aerobic gram-negative bacilli by the time of
      transplant surgery. This is an especially important point because successful SBD
      requires at least several days of treatment, and there are practical problems
      initiating and maintaining SBD in advance of unscheduled cadaver liver
      transplantation. Key areas for investigation are to establish by appropriately
      designed studies the efficacy of SBD and to examine the importance of achieving
      SBD prior to transplantation surgery.

PMID- 8747770
TI  - Cytomegalovirus infection in organ transplant recipients.
AB  - Cytomegalovirus (CMV) continues to be responsible for a substantial fraction of
      the morbidity and mortality that follows organ transplantation. The three major
      consequences of CMV infection are CMV disease (encompassing a range of clinical
      illness), superinfection with opportunistic pathogens, and injury to the
      transplanted organ. In the last decade, considerable progress has been made in
      elucidating risk factors for CMV disease, in rapid detection of CMV in clinical
      specimens, and in the use of antiviral chemotherapy and immunoglobulin to prevent
      and treat CMV disease after transplantation. This article discusses the impact of
      these advances on patient outcome following transplantation and the challenges
      for the next decade.

PMID- 8747771
TI  - Cytomegalovirus infection in the bone marrow transplant recipient.
AB  - Over the past 5 years, with the introduction of preventive ganciclovir therapy
      and a better understanding of the immunology of cytomegalovirus (CMV) in bone
      marrow transplant (BMT) recipients, there has been a significant change in the
      management of CMV infection. As the field of BMT has moved into this era of
      prophylaxis, there are new problems posed by CMV infection that require
      additional attention. The natural course of CMV-associated disease is undergoing
      a change, with a frame-shifting of disease onset to later times after BMT. Yet,
      the success of this antiviral prophylaxis has been of central importance of new
      developments in marrow transplantation. At the same time that these new antiviral
      approaches have developed, there has been intensive interest in reducing the cost
      of BMT. With this, there is a concern for use of the available antiviral
      strategies in the most efficient manner. This article reviews the various
      management options relating to control of CMV and discusses certain areas
      relating to new research strategies that promise to provide even better
      approaches to the problem of CMV in this population.

PMID- 8747772
TI  - Post-transplant lymphoproliferative disorder.
AB  - This article discusses the virology of Epstein-Barr virus (EBV) and provides an
      overview of the disease states associated with the virus, describes how the
      immunology of EBV infection provides for control in the normal host, and reviews
      what is currently known about post-transplant lymphoproliferative disorder
      (PTLD), including evidence for EBV in the pathogenesis of PTLD, risk factors for
      its development, clinical presentation, methods for diagnosis, pathology,
      treatment, and current and future preventive strategies.

PMID- 8747773
TI  - Hepatitis B and transplantation.
AB  - Hepatitis B infection can add significantly to the morbidity and mortality of
      transplantation. Patients with hepatitis B can have severe recurrent disease
      following liver transplantation. Reactivation of occult disease can occur during
      chemotherapy or immunosuppression. Hepatitis B also can be acquired at the time
      of transplantation. Intensive study of transplant patients with hepatitis B has
      led to a new understanding of the immunobiology of hepatitis B virus.

PMID- 8747774
TI  - Hepatitis C infection in the transplant recipient.
AB  - This article highlights the increasing role of HCV in the transplant setting. Its
      importance in the liver transplant setting is clear. It produces end-stage liver
      disease and represents a common indication for transplant referral. Recurrent
      infection is nearly universal posttransplant in those with viremia pretransplant.
      Acquired disease is uncommon. The natural history of posttransplant disease
      suggests there is no significant impact of graft or patient survival, at least in
      the short-term. Long-term follow-up is needed, as well as more detailed study of
      the factors contributing to posttransplant disease. Kidney transplant patients
      commonly are infected with HCV prior to transplantation. Acquisition of infection
      through infected donors also serves as a source of HCV infection. HCV infection
      after transplantation is associated with an increased risk of liver disease but
      has no significant effect on short-term patient survival. The issues of organ
      allocation from anti-HCV-positive donors are particularly relevant to this
      patient population because maintenance dialysis always is a treatment alternative
      to transplantation. Much less information is available on other transplant
      groups, such as heart, lung, and bone marrow transplant recipients. There are
      many unanswered questions, especially with respect to the natural history of
      disease after 5 to 10 years of infection. The pathogenesis of infection in the
      transplant setting is emerging slowly but requires further investigation. Both
      direct viral cytopathicity and host-mediated immunity appear to play a role in
      liver injury. An increased understanding of pathogenicity will lead to improved
      management of patients with HCV infection both pre- and posttransplant.

PMID- 8747775
TI  - Management of the transplant recipient with pulmonary infection.
AB  - Pneumonia is a common and potentially fatal complication of transplantation. The
      clinical approach to this problem requires a multipronged attack. Thorough
      evaluation of the donor and recipient reduces the risk of infection while
      pointing to likely infectious complications to be anticipated posttransplant.
      Careful attention to infection control measures with emphasis on handwashing,
      high efficiency particulate air filtration, and aggressive outbreak investigation
      minimizes nosocomial pneumonias. Appropriate use of vaccines and prophylactic
      antimicrobial therapies decreases posttransplant morbidity and mortality. Once
      pneumonia occurs, a rapid, thorough diagnostic evaluation increases the
      likelihood of survival for the individual patient and focuses attention on
      environmental risks that may pose a hazard to the other transplant recipients in
      the clinician's institution.

PMID- 8747776
TI  - Orthomyxoviral and paramyxoviral infections in transplant patients.
AB  - In summary, orthomyxo- and paramyxoviruses cause clinically important infections
      in transplant patients. Patients often develop lower respiratory tract
      involvement and sometimes respiratory failure, which almost is uniformly fatal.
      Bone marrow transplant recipients appear to be at higher risk of severe disease
      than are solid-organ recipients, but well defined criteria to predict those
      patients who will be severely affected are not available. Factors associated with
      more severe disease include the type of viral pathogen, with pneumonia occurring
      more commonly with RSV and PIV infection, and the degree of immunosuppression of
      the patient, particularly the pre-engraftment phase in bone marrow transplant
      recipients. Because mortality is associated with development of pneumonia, prompt
      diagnosis and studies for concurrent infections are essential. Evaluation of
      fever and upper respiratory tract symptoms in patients in the peritransplant
      period should include sampling of nasopharyngeal and throat for virus isolation
      and antigen detection for respiratory viruses. If patients develop lower
      respiratory tract symptoms, early bronchoscopy with BAL is indicated. No specific
      antiviral therapy has proved effective in the treatment of established
      respiratory viral infections of transplant patients. Aerosolized ribavirin or, in
      the instance of influenza A virus infection, oral rimantadine might be considered
      as early therapy to prevent severe lower respiratory disease. Intravenous
      ribavirin, currently available on a compassionate use basis, might be considered
      for treating measles virus infection. In patients with lower tract disease due to
      RSV, the addition of immunoglobulin with high neutralizing antibody titers to RSV
      or intravenous ribavirin are additional considerations to forestall respiratory
      failure. Controlled studies of these interventions are needed in transplant
      patients before their use can be recommended routinely.

PMID- 8747777
TI  - Pneumocystis carinii and parasitic infections in transplantation.
AB  - Pneumocystis carinii remains an important pathogen in organ transplantation. New
      therapeutic options have been developed for the prevention and treatment of P.
      carinii pneumonia. Parasitic infections are recognized more frequently in
      potential organ donors or recipients as travel and technology for transplantation
      extend into endemic regions. Parasites important to transplantation are largely
      those that can replicate in humans and that cause infection, the intensity of
      which is regulated by immune mechanisms in the normal host. The spectrum of
      parasitic infections is likely to increase with improved diagnostic methods,
      expansion of intestinal transplantation, and xenotransplantation.

PMID- 8747778
TI  - Fungal infections in solid organ transplant recipients.
AB  - Invasive fungal infections occur in 5% to 45% of solid organ transplant
      recipients, and are a major cause of morbidity and mortality in the
      immunocompromised population. The net depression of host defenses and
      environmental factors, such as preoperative exposures to endemic mycoses or
      nosocomial and specific surgery-associated exposures, affect the development of
      invasive infection. Most fungal infections in solid organ transplant recipients
      occur within the first 2 months after transplantation. The most common pathogens
      in the majority of solid organ transplant recipients are Candida spp, followed by
      Aspergillus sp. Diagnosis is best made by a high index of suspicion and
      aggressive acquisition of specimens for culture; serologic tests are useful for
      infections due to Cryptococcus neoformans and Histoplasma capsulatum.
      Amphotericin B is the drug of choice for life-threatening infections. The
      triazoles, fluconazole and itraconazole, may be effective alternatives for less
      serious infections due to susceptible organisms. Prophylactic and preemptive
      treatment strategies require further study.

PMID- 8747779
TI  - Characterization of endothelin receptor subtypes in isolated rat renal
      preglomerular microvessels.
AB  - Endothelin (ET) increases renal vascular resistance by constriction of post- and
      preglomerular vessels in the rat. However, ET receptor subtypes in renal
      microvessels have not been clearly defined. Radioligand binding experiments were
      performed in isolated arcuate and interlobular arteries as well as branching
      afferent arterioles to characterize 125I-ET-1 binding sites. Competitive
      inhibition assays were performed with ET-1, ET-2, ET-3, sarafotoxin 6b (S6b), BQ
      123 (a preferential ETA receptor antagonist) and 4-Ala-ET-1 (a preferential ETB
      receptor agonist). Saturation data revealed a single class of high affinity
      binding sites with a kd of 0.31 +/- 0.03 nM and a Bmax of 1336 +/- 181 fmol/mg
      protein. Competitive inhibition of 125I-ET-1 binding showed that all assayed
      compounds displaced 125I-ET-1 in a dose-related manner. ET-1 displaced 100% of
      125I-ET-1 binding, displaying monophasic curves with Bmax and kd values of 1369
      +/- 170 fmol/mg protein and 0.35 +/- 0.04 nM, respectively. ET-2's displacement
      curves were similar to those of ET-1. ET-3 and S6b inhibited 100% of 125I-ET-1
      binding in a biphasic manner, suggesting these peptides bind both high and low
      affinity sites. BQ-123 displaced about 50% of 125I-ET-1 in a monophasic manner,
      indicating a single high affinity binding site. 4-Ala-ET-1 displaced 125I-ET-1 in
      a clearly biphasic manner with an almost equal proportion of high and low
      affinity binding sites. Our results suggest that both ETA and ETB receptors are
      expressed in rat renal preglomerular vessels in almost equal proportions.
      However, the characteristics of competitive inhibition of 125I-ET-1 binding by
      several agents cannot be fully explained by a two-receptor model.

PMID- 8747780
TI  - Time-dependent decreases of atrial natriuretic peptide release from the isolated
      rat atrium: evidence for a readily releasable pool.
AB  - In vitro, atrial distension causes a rapid increase in atrial natriuretic peptide
      (ANP) release. This stretch-induced release, however, declines to baseline levels
      within minutes without significant depletion of the total hormone stores. It has
      been observed that the basal rate of ANP release from isolated atria also
      declines over time despite evidence that the tissue retains its viability. We
      examined this time-dependency of ANP release from isolated rat atria and some
      parameters that may explain the diminishing release. Mean ANP secretion was 60
      pg/min for both spontaneously beating and electrically paced preparations.
      Although ANP secretion steadily declined over time, there was no time-dependent
      effect on the amplitude of intracellularly recorded action potentials. The total
      ANP content in atria obtained after dissection was 133 +/- 28.9 micrograms/g (n =
      3) which was not significantly different from atria that were perfused for 3 h
      (137 +/- 21.2 micrograms/g; n = 3). Only the 28 amino acid circulating form of
      ANP was released. The ANP mRNA appeared to be partially degraded in atria after
      30 min equilibration or after perfusion for 3 h. These results demonstrated that
      ANP release from isolated atrial preparations declines steadily despite the
      maintenance of normal electrophysiological activity. This decline was not due to
      significant depletion of the ANP stores suggesting that a readily releasable pool
      of ANP exists and represents only a small fraction of the total hormone stores.
      Finally, degradation of ANP mRNA implies a reduction of de novo synthesis in our
      preparation which suggests that the observed depletion of the releasable pool was
      related to a decline in newly synthesized ANP.

PMID- 8747781
TI  - Neuropeptide Y is expressed in subpopulations of insulin- and non-insulin
      producing islet cells in the rat after dexamethasone treatment: a combined
      immunocytochemical and in situ hybridisation study.
AB  - Neuropeptide Y (NPY) is known to occur in adrenergic and non-adrenergic nerves in
      rat pancreatic islets. Analysis of islet extracts has revealed local NPY
      synthesis after glucocorticoid treatment. The cellular localisation of NPY
      expression in rat islets following dexamethasone treatment (2 mg/kg daily, for 12
      days), was investigated by a combination of immunocytochemistry (ICC) and in situ
      hybridisation (ISH). NPY-immunoreactive nerve fibres were seen in pancreatic
      islets of both control and dexamethasone-treated rats. In the controls weak NPY
      immunoreactivity but no NPY mRNA was observed in occasional islets. After
      dexamethasone treatment, clusters of islet cells distributed both centrally and
      peripherally displayed intense NPY immunoreactivity and NPY mRNA labelling.
      Immunocytochemical double staining and ISH combined with ICC for NPY and islet
      hormones revealed that most NPY expressing cells were identical with insulin
      cells; a few cells were identical with somatostatin or pancreatic polypeptide
      (PP) cells. In contrast, glucagon cells seemed to be devoid of NPY
      immunoreactivity and NPY mRNA labelling. Thus, in the rat, glucocorticoids cause
      a marked upregulation of NPY expression in islet cells, preferentially the
      insulin cells. The expression of NPY might represent an islet adaptation
      mechanism to the reduced peripheral insulin sensitivity.

PMID- 8747782
TI  - Control of gallbladder contractions by cholecystokinin through cholecystokinin-A
      receptors in the vagal pathway and gallbladder in the dog.
AB  - The mechanism of CCK action on gallbladder contractions in the physiological
      condition is unclear. Gallbladder contractions were monitored by means of
      chronically implanted force transducers in conscious dogs. Postprandial
      gallbladder contractions were partially inhibited by atropine and hexamethonium,
      and completely inhibited by devazepide. In vitro contractile response of canine
      gallbladder muscle strips to CCK-8 was also studied. CCK-8-induced muscle strip
      contraction was atropine and tetrodotoxin resistant, but was completely
      eliminated by devazepide. The existence of CCK receptors in the vagal nerve and
      gallbladder was examined by means of autoradiography. Forty-eight hours after
      ligation of the abdominal vagus, CCK-8 binding sites were found to accumulate in
      the subdiaphragmatic vagal nerve immediately proximal to the ligature, and
      similar binding sites were also found in the gallbladder smooth muscle layer.
      These binding sites were displaced by the addition of 10(-7) mol/1 unlabeled CCK
      8 and devazepide, but L-365,260 had no effect. In conclusion, it is considerable
      that postprandial CCK-induced gallbladder contractions are controlled through CCK
      A receptors both on the vagal nerve in stimulating endogenous release of
      acetylcholine and on the gallbladder directly to stimulate muscle contraction in
      the dog.

PMID- 8747783
TI  - Central and peripheral cholecystokinin receptors in chickens differ from those in
      mammals.
AB  - Specific binding for the radioligand [3H]CCK-8s has been identified in chicken
      brain, hypothalamus, pancreas, gallbladder and caecum membranes. This binding was
      found to be of high affinity, low capacity and saturable, suggesting the presence
      of specific CCK receptors in these tissues. Scatchard analysis indicated the
      existence of a single binding site for each tissue. Dissociation constant (kd)
      values were 0.63 +/- 0.18, 0.73 +/- 0.13, 0.85 +/- 0.12, 1.47 +/- 0.21 and 0.96
      nM for brain, hypothalamus, pancreas, caecum and gallbladder, respectively.
      Binding densities (Bmax) were higher for brain, pancreas and caecum (32.60 +/-
      10.70, 30.33 +/- 2.40 and 35.83 +/- 5.10 fmol/mg protein, respectively) than for
      the other two tissues (9.75 +/- 1.90 and 6.31 fmol/mg protein for hypothalamus
      and gallbladder, respectively). As in mammals, CCK-4 shows high affinity for CCK
      receptors located in chicken brain and hypothalamus, and very low affinity for
      those located in peripheral structures. L-364,718 (a CCK-A antagonist) showed a
      relative selectivity and a high affinity for those receptors located in central
      tissues, whereas L-365,260 (a CCK-B antagonist) is almost inactive in all studied
      tissues. These results give support for the existence of at least two distinct
      CCK receptors in birds and that these receptors are relatively different from
      those described in mammals.

PMID- 8747784
TI  - Tachykinins stimulate nitric oxide generation by canine cultured tracheal
      epithelium.
AB  - We studied the effects of tachykinins on the generation of nitric oxide (NO) from
      canine cultured tracheal epithelial cells using a specific amperometric sensor
      for this molecule. Immersion of the NO-selective electrode in the medium bathing
      the cells detected the baseline current of 30.5-61.7 pA, which corresponded to NO
      concentration ([NO]) at 44.0 +/- 7.6 nM (mean +/- S.E.M.). Substance P (SP, 10(
      6) M) increased the current from 51.3 +/- 9.8 to 73.6 +/- 11.4 pA (P < 0.001), an
      effect that was not affected by NG-nitro-D-arginine methylester, but inhibited by
      NG-nitro-L-arginine methylester by 83 +/- 9% (P < 0.001), and this inhibition was
      restored by the subsequent addition of L-arginine, but not by D-arginine. SP and
      neurokinin A (NKA) increased [NO] in a dose-dependent manner, the maximal
      increases from the baseline level being 71.0 +/- 14.9 and 33.4 +/- 8.5 nM,
      respectively (P < 0.001 for each), whereas neurokinin B (NKB) had no effect. In
      the presence of phosphoramidon, the response of each tachykinin was augmented,
      but the rank order of potency was still NKA > SP >> NKB. These results suggest
      that NO is spontaneously released from airway epithelium and that tachykinins
      stimulate epithelial NO generation via NK2 receptors.

PMID- 8747785
TI  - Insulinotropic effects of cholecystokinin, gastric inhibitory polypeptide and
      glucagon-like peptide-1 during perifusion of short-term cultured canine isolated
      islets.
AB  - Recent metabolic studies suggest that the incretin effect of gut hormones may
      account for most of the circulating insulin during mild postprandial
      hyperglycemia after transplantation of isolated islets. As yet, however,
      insulinotropic effects of pharmacological rather than physiological levels of the
      incretin candidates cholecystokinin-33 (CCK-33), gastric inhibitory polypeptide
      (GIP), and glucagon-like peptide-1 (GLP-1) on isolated perifused islets have been
      reported. We examined the insulinotropic effects of these peptides during
      perifusion of canine isolated islets. Exploration of beta-cell sensitivity in our
      model with graded 0.1-10 nM doses of CCK-33 and GIP at a 7.5 mM glucose level
      demonstrated insulinotropic effects from the lowest level. We, therefore, focused
      on the (near-) physiological effects of both CCK-33 (20 pM), GIP (500 pM), and
      GLP-1 (100 pM) during perifusion at a 2.5, 7.5, and 10 mM glucose level. No
      effects of CCK-33 were observed. GIP enhanced insulin release 1.1- and 1.2-fold,
      at the 7.5 and 10 mM glucose level, respectively. GLP-1 stimulated insulin output
      from the 2.5 mM glucose level; and a maximum, 2-fold, increase of insulin output
      was observed from the 7.5 mM glucose level. Thus, isolated perifused islets do
      respond to near-physiological beta-cell stimulation with gut hormones, and both
      GIP and GLP-1 may contribute to a hyperglycemia-enhanced activation of the
      enteroinsular axis after transplantation of isolated islets.

PMID- 8747786
TI  - Effect of [1-Sar,8-Thr]-angiotensin II on the hyperglycemic response to
      hemorrhage in adrenodemedullated and guanethidine-treated rats.
AB  - The present experiments were designed to further investigate the action of an
      angiotensin II antagonist on the hyperglycemic response to hemorrhage (1.2 ml/100
      g b.wt./2 min). The animals were divided into 3 experimental groups; (1) sham
      operated animals submitted to intravenous administration of [1-Sar,8-Thr]
      angiotensin II (sarthran), an antagonist of angiotensin II (750 ng/100 g b.wt. as
      a bolus plus an infusion of 25 ng/100 g b.wt./min over 30 min), which greatly
      attenuated (51.8% lower than controls; P < 0.01) the hyperglycemic response to
      hemorrhage; (2) animals submitted to adrenodemedullation which decreased the
      hyperglycemic response to hemorrhage by 64% (P < 0.01). However, sarthran
      infusion into adrenodemedullated rats caused a 38.5% further decrease in
      hyperglycemic response to hemorrhage (P < 0.01); and (3) intact animals submitted
      to blockade of sympathetic noradrenergic pathways by treatment with guanethidine
      (10 mg/100 g b.wt.), which greatly decreased the baseline value of plasma glucose
      (64.1 +/- 3.5 mg% vs. 125.3 +/- 4.5 mg%, P < 0.01), and reduced the hyperglycemic
      response to hemorrhage by 34% (P < 0.01). Sarthran infusion into guanethidine
      treated rats caused a further 34% decrease in hyperglycemic response to
      hemorrhage (P < 0.01). These data indicate that angiotensin II has a direct
      hyperglycemic effect in addition to its action on sympathetic nervous system
      activation and adrenomedullary secretion.

PMID- 8747787
TI  - Requirement for prostaglandin synthesis in secretion of atrial natriuretic factor
      from isolated rat heart.
AB  - Release of atrial natriuretic factor (ANF) from the heart is primarily affected
      by myocyte stretch. In addition, ANF release can be modulated by a variety of
      hormones and neurotransmitters, but the mechanisms involved in such modulation
      are not completely understood. In the present study, we investigated the effect
      of inhibition of cyclooxygenase activity on release of ANF from the isolated,
      spontaneously beating rat heart: (1) during basal conditions; and (2) in response
      to arginine vasopressin (AVP), acetylcholine (ACh) and angiotensin II (ANG II),
      in order to determine if cardiac prostaglandin synthesis is involved in
      modulation of basal and hormone-mediated ANF secretion. Basal secretion in the
      time controls remained stable for the duration of the experiment. AVP, ACh and
      ANG II reduced basal secretion significantly by 58 +/- 4%, 51 +/- 6% and 26 +/-
      8%, respectively, independently of concomitant changes in coronary flow and heart
      rate. Inhibition of cyclooxygenase with indomethacin (1 x 10(-5) M) decreased
      basal ANF release by 38 +/- 6%, indicating that basal secretion requires
      prostaglandin production. The effects of AVP, ACh and ANG II were maintained
      during perfusion with indomethacin, suggesting a common mechanism of action which
      operates via inhibition of cyclooxygenase. Based on our previous findings that
      the effects of indomethacin, AVP and ACh are overcome by inhibition of NO/EDRF
      synthesis, we suggest a common mechanism of action by means of which NO/EDRF
      mediates the effects of these agents by inhibiting cyclooxygenase activity.

PMID- 8747788
TI  - Beta adrenergic receptors facilitate norepinephrine release from rat hypothalamic
      and hippocampal slices.
AB  - Basal and electrical stimulation-induced release of tritiated norepinephrine (3H
      NE) was determined in superfused slices of the rat hypothalamus and hippocampus.
      Isoproterenol (0.1-10 nM), a nonselective beta-adrenergic agonist, enhanced
      stimulation-evoked release of 3H-NE from hypothalamic and hippocampal slices in a
      concentration-dependent manner without consistently altering basal release.
      Isoproterenol (1 nM) increased ratios of S2/S1 to 143 +/- 4% (hypothalamus) and
      152 +/- 15% (hippocampus) of control values. The facilitatory effects of
      isoproterenol were antagonized by propranolol (50 nM), a nonselective beta
      adrenergic antagonist. The beta 2-selective adrenergic agonist clenbuterol (10
      100 microM) enhanced basal release of 3H-NE in a concentration-dependent fashion.
      These results provide evidence for a beta-adrenergic receptor mediated regulation
      of NE release from hypothalamic and hippocampal slices. Whether the positive
      feedback mechanism contributes to any of the NE-mediated physiological functions
      associated with the hypothalamus and hippocampus requires further study. However,
      the effect of clenbuterol indicates that some of its behavioral actions in
      animals may be attributed to this NE release-enhancing effect observed in the
      present study.

PMID- 8747789
TI  - Abnormal hepatic copper accumulation of spheroid composed of liver cells from LEC
      rats in vitro.
AB  - The LEC rat is a mutant strain displaying hereditary hepatitis, and shows
      abnormal accumulation of copper (Cu) similar to that occurring in Wilson's
      disease. We prepared a multicellular spheroid composed of LEC rat liver cells to
      investigate the mechanism for abnormal accumulation of Cu. These multicellular
      spheroids were prepared by detaching the monolayer on the collagen-conjugated
      thermo-responsive polymer coated culture dish at a temperature below the critical
      solution temperature and culturing on the non-adhesive substratum. Long-term
      cultured spheroids of LEC rat liver cells as well as SD rat liver cells were
      attempted. Non-parenchymal cells obtained by collagenase perfusion from the LEC
      liver were fewer than those from the SD liver. Cells from the LEC rat, over 11
      weeks of age, did not form a cell sheet; however, a mixture of parenchymal cells
      from LEC rats over aged 11 weeks and non-parenchymal cells from SD rats of any
      age yielded intact spheroids. We examined the toxicity, the accumulation and
      distribution of Cu in spheroids. The accumulation of Cu in LEC spheroids was
      higher than that in SD spheroids. Results suggest that spheroids consisting of
      LEC liver cells are useful as an alternative model to in vivo tests to
      investigate the mechanism for abnormal accumulation of Cu in liver.

PMID- 8747790
TI  - Induction of differentiation of embryonal carcinoma F9 cells by iron chelators.
AB  - The effects of several chelators, including hinokitiol, on embryonal carcinoma F9
      cell differentiation were assessed by assaying the production of plasminogen
      activator (PA) as a differentiation marker protein. Hinokitiol and tropolone
      which were potent differentiation inducers lost their activity following
      preincubation with Fe2+ and Fe3+ ions. Other metal ions had no or little effect
      on the hinokitiol-induced differentiation. Of several chelators examined,
      dithizone induced differentiation as effectively as did hinokitiol and tropolone.
      Dithizone-induced differentiation was also inhibited by preincubation with Fe3+
      ions. It was concluded that some potent iron chelators could trigger the
      teratocarcinoma F9 cells to differentiate through the chelation with
      intracellular iron ions.

PMID- 8747791
TI  - Biological effects of diesel exhaust particles (DEP) on tissues and cells
      isolated from respiratory tracts of guinea pigs.
AB  - Diesel engine-powered vehicles emit some 30 to 100 times more particles than do
      gasoline engine cars. We previously reported that diesel exhaust particles (DEP)
      instilled intratracheally into mouse caused lung edema accompanying endothelial
      cell damage. In order to clarify further the biological effects of DEP on the
      respiratory system, the primary target of DEP instillation, we examined the
      direct action of DEP on isolated tissues and the cytotoxicity of DEP on cultured
      cells of respiratory tracts in guinea pigs. DEP were collected on glass fiber
      filters from a light-duty (2730 cc), four cylinder diesel engine. DEP induced a
      dose-dependent relaxation in tracheal smooth muscle and lung parenchymal
      preparations from guinea pigs. Neither propranolol nor ranitidine inhibited the
      relaxing effect of DEP on tracheal preparations. DEP also exhibited concentration
      and time-dependent cytotoxicity on cultured tracheal smooth muscle cells and
      lung fibroblasts from guinea pigs, as assessed by specific [51Cr] release. These
      cytotoxicities induced by DEP were significantly inhibited by catalase,
      deferoxamine and MK-447, whereas SOD and mannitol had little effect. These
      inhibitory effects were blunted by the higher concentration of DEP. These results
      suggest that the cytotoxicity of DEP may cause dysfunction of respiratory
      tissues, which are mediated via oxygen radicals, probably hydroxyl radicals or
      hydrogen peroxides.

PMID- 8747792
TI  - Effect of NDGA on beef heart mitochondria and EMT6 mouse mammary carcinoma cells.
AB  - The inhibition of mitochondrial succinate cytochrome c reductase by
      nordihydroguaiaretic acid (NDGA) was measured in vitro under aerobic and hypoxic
      conditions. The photodynamic effect of NDGA on EMT6 mouse mammary carcinoma cells
      was also investigated in vitro under aerobic and hypoxic conditions. NDGA
      strongly inhibited succinate cytochrome c reductase, which contains the
      mitochondrial electron transport Complexes II and III. By comparing the I50
      values of aerobic and hypoxic assays, NDGA inhibition was found to be oxygen
      independent. This finding suggests that oxygen is not involved in the inhibitory
      effect of mitochondrial respiration by NDGA. Similarly, our data demonstrate that
      NDGA-induced cytotoxicity towards EMT6 tumor cells is neither light-dependent nor
      oxygen-dependent. A dose-dependent loss of viability of EMT6 cell was observed
      although the toxicity of NDGA towards EMT6 cells was not strong, with an LC50 in
      the 200 microM range. NDGA caused a depletion of mitochondrial sulfhydryl groups.
      Sulfhydryl compounds, GSH and cysteine, prevented the inhibition of succinoxidase
      activity by NDGA. This suggests that NDGA exerts its biological effects by the
      depletion of sulfhydryl groups in key biochemical systems related to
      mitochondrial function.

PMID- 8747793
TI  - Dominant contribution of 5-hydroxytryptamine over thromboxane A2 in contractile
      response of rabbit isolated aortic preparation to thrombin activated platelets.
AB  - Activated platelets release two potent vasoconstrictors: viz., 5
      hydroxytryptamine (5-HT) and thromboxane A2 (TXA2). The aim of the present study
      is to clarify which of these vasoconstrictors released from activated platelets
      acts more predominantly on the vascular smooth muscle. The increase of
      intraluminal pressure, which is due to the vascular smooth muscle contraction, of
      isolated rabbit aortic preparation in response to 5-HT or STA2, a stable analog
      of TXA2 was significantly greater when these drugs applied from the intimal
      surface than when applied from adventitial surface. The contractile response to 5
      HT or TXA2 was markedly depressed by the treatment with methysergide, a 5-HT
      receptor antagonist or ONO 3708, a TXA2 receptor antagonist, respectively.
      Thrombin administered from intimal or adventitial surface had almost no effect.
      However, thrombin administered from intimal or adventitial surface in the
      presence of washed platelets produced a marked contraction. The contractile
      response to thrombin in the presence of washed platelets was almost unaffected by
      the treatment with ONO 3708, while it was completely depressed by the treatment
      with methysergide. These findings may indicate that 5-HT released from activated
      platelets by thrombin contributes more dominantly to the contractile response of
      the vascular smooth muscle than TXA2.

PMID- 8747794
TI  - Effects of VA-045, a novel apovincaminic acid derivative, on rabbit basilar
      artery.
AB  - We investigated the effects of VA-045, an apovincaminic acid derivative, on
      isolated basilar artery of the rabbit. In basilar artery precontracted with
      histamine (10(-6) M), VA-045 (10(-9) to 10(-5) M) produced a concentration
      dependent relaxation, but VA-045-induced relaxation was significantly reduced
      when the tonus of the mesentery was raised by isotonic high K+ (30 or 65 mM) or
      histamine (10(-6) M) with 15 mM K+. VA-045-induced relaxations of the basilar
      artery were not affected by 10 mM tetraethylammonium (TEA), 10(-6) M 4
      aminopyridine, 10(-6) M charybdotoxin, 10(-7) M apamin and 10(-6) M
      glybenclamide. VA-045-induced relaxation was not influenced by 10(-5) M methylene
      blue. These results suggest that increased open probability of potassium
      channels, which are not Ca(2+)-dependent K(+)-channels or TEA- or ATP-sensitive
      K(+)-channels, may be involved in VA-045-induced relaxation of basilar artery.

PMID- 8747795
TI  - Blood levels of endothelin-1 and thrombomodulin in patients with disseminated
      intravascular coagulation and sepsis.
AB  - We evaluated the roles of plasma endothelin-1 and plasma thrombomodulin in the
      development of disseminated intravascular coagulation (DIC) in patients with
      sepsis. Plasma endothelin-1 was measured by radioimmunoassay (RIA). Plasma
      thrombomodulin and tumor necrosis factor-alpha (TNF-alpha) were measured by
      enzyme-linked immunosorbent assay (ELISA), and serum protein C (protein C) was
      measured by the synthetic substrate method. Endotoxin was measured by the
      Endospecy test, a synthetic substrate method. A new perchloric acid method was
      used for the pretreatment of plasma. Blood levels of endothelin-1 and
      thrombomodulin were significantly higher in patients with DIC than in those
      without DIC (p < 0.0001). Endothelin-1 and thrombomodulin levels were positively
      correlated (r = 0.8645, p = 0.0001), as were endothelin-1 and TNF-alpha levels (r
      = 0.5441, p = 0.0002). Thrombomodulin and protein C levels were negatively
      correlated (r = -0.5627, p = 0.0001). Endotoxin was elevated above the normal
      level 14.3% (6/42) for these patients. TNF-alpha is involved in the production of
      endothelin-1 and thrombomodulin, which play a role in the pathogenesis of DIC and
      whose blood levels reflect its severity.

PMID- 8747796
TI  - Effect of pentobarbital anesthesia on the pressor response to agonists in vivo in
      normal and endotoxemic rats.
AB  - Studies of cardiovascular physiology are frequently performed under barbiturate
      anesthesia even though the effect of barbiturates on the pressor response to
      catecholamines is controversial, and their effect on the response to other
      agonists is unknown. The effect of pentobarbital (PB) anesthesia on the pressor
      and heart rate (HR) dose responses to norepinephrine (NE), angiotensin II (AII),
      vasopressin (VP) and neuropeptide Y (NPY) was studied in vivo in normal and
      endotoxemic rats. Four groups of rats (5-6 rats/group) were studied for each
      agonist: 1) anesthetized/endotoxemic, 2) anesthetized/control, 3)
      conscious/endotoxemic, and 4) conscious/control. Anesthesia was maintained with
      10 mg/kg of PB i.v. q 45 minutes. Endotoxemia was established by infusion of a
      non-hypotensive dose of E. coli lipopolysaccharide 0127:B8, (LPS, 10
      micrograms/10 microliters/min) throughout the experiment. One hour after the LPS
      (or saline control) infusion was started, dose response curves of the pressor and
      HR responses to agonists were established. LPS infusion resulted in marked
      suppression of the pressor response to NE, AII, and VP in both conscious and
      anesthetized rats. LPS infusion suppressed the response to NPY in conscious, but
      not in anesthetized rats. LPS did not affect the baroreceptor reflex. In both
      normal and endotoxemic rats, PB anesthesia suppressed the pressor response and
      attenuated the baroreceptor reflex to AII and NPY, enhanced the pressor response
      without affecting the heart rate response to NE, and attenuated the baroreceptor
      reflex to VP. The pressor response to VP was suppressed by anesthesia in normal,
      but not in endotoxemic rats. PB anesthesia interferes with the cardiovascular
      effects of different agonists in a variable manner, depending on the agonist
      tested and the presence or absence of endotoxemia, indicating their different
      modes of action. These effects should be considered when planning in vivo
      experiments with these and other agonists.

PMID- 8747797
TI  - Serum gastrin levels in patients with colorectal cancer and adenomatous polyps: a
      prospective study.
AB  - Serum gastrin levels were measured by radioimmunoassay in 62 patients with
      colorectal neoplasms (40 with adenomatous polyps and 22 with cancer) and 40
      controls. Fasting serum gastrin in both the polyp (73.93 +/- 6.5 pg/ml) and the
      cancer (99 +/- 19.7 pg/ml) groups was significantly higher than those of the
      control group (42.65 +/- 2.2 pg/ml). These findings suggest that hypergastrinemia
      may be an etiologic factor in colorectal neoplasia.

PMID- 8747798
TI  - Bronchial hyperresponsiveness in children and adolescents.
AB  - The frequency distribution of bronchial responsiveness to both inhaled histamine
      and exercise both exhibit a unimodal distribution, different from a normal
      distribution, whereas PC20 values exhibited a lognormal distribution. BHR to both
      inhaled histamine (PC20 < or = 8.0 mg/ml (21 (II))) and exercise (delta % FEV1 <
      or = 10% (22 (III)) was found in 16% of the children and adolescents, while 6% of
      the population had BHR to both stimuli (22 (III)). Although a significant
      relationship between responsiveness to inhaled histamine and exercise existed (rs
      = 0.3, p < 0.001), the lack of overlap indicates that the association between the
      two stimuli is more complex (20 (I)). Worldwide, considerable differences in the
      prevalence of children with BHR to both inhaled agents and exercise have been
      observed. The prevalence of BHR to histamine and exercise observed in the present
      study was similar to findings in other industrialized countries, while the
      prevalence of BHR in e.g. Africa is low. All subjects with asthma had BHR to
      histamine and 77% had BHR to exercise, but only 35% of those with BHR to
      histamine (20 (I)) and 25% of those with BHR to exercise (delta FEV1 > or = 10%)
      (22 (III)) had symptomatic asthma. Thus low PVpos indicates that bronchial
      challenges are inadequate tools for screening in epidemiologic studies of asthma.
      The present study, however, showed that the predictive values of a negative test
      (PVneg) was high (100% (23 (IV) and 99% (22 (III)), respectively) supporting that
      bronchial challenge testing can exclude the diagnosis of asthma. Furthermore,
      asymptomatic subjects with BHR had reduced increase in height and lung function
      (FEV1) during the follow-up period of 18 months. The present observation indicate
      that BHR may induce permanent impairment of the lung function. The degree of
      responsiveness was significantly influenced by the presence of asthmatic symptoms
      and atopy of which house-dust mites and horse epithelium were of specific
      importance, whereas no association was demonstrated between BHR and recent viral
      infection, smoke or level of lung function. In conclusion, BHR is frequently
      observed in population samples and the degree of responsiveness was closely
      related to asthma and atopy. In children and adolescents with BHR, the increased
      responsiveness remained unchanged and those who developed asthma had a
      preexisting asymptomatic BHR.

PMID- 8747799
TI  - Diet, blood coagulation and fibrinolysis.

PMID- 8747800
TI  - Motor activity of the gallbladder and gastrointestinal tract as determinants of
      enterohepatic circulation. A scintigraphic and manometric study.

PMID- 8747801
TI  - The Na+/K(+)-pump in rat peritoneal mast cells: some aspects of regulation of
      activity and cellular function.
AB  - The mast cell contains potent mediators of inflammation which are released after
      IgE-directed and non-IgE-directed stimulation of the cell. This highly
      specialized cell is therefore ascribed a role in the pathogenesis of disease
      states in which the inflammatory response plays a role for the development of the
      clinical symptoms. Thus, besides being of interest in basic research, studies of
      the cellular processes leading to release of inflammatory mediators from the mast
      cell also have important clinical implications. The aim of the present work has
      been to document the existence of the Na+/K(+)-pump in rat peritoneal mast cells,
      to investigate the regulation of the pump activity and to explore whether
      modulation of the pump activity interferes with the cellular stimulus/secretion
      coupling mechanism. The Na+/K(+)-pump activity following stimulation of the mast
      cell was also investigated. The pump activity was assessed as the ouabain
      sensitive cellular potassium uptake with 86Rb+ as a tracer for potassium. The
      histamine release from the mast cell following IgE-directed and non-IgE directed
      stimulation of the cell was used as a parameter for cellular degranulation.
      Histamine was measured by spectrofluorometry. The finding of an ouabain-sensitive
      uptake mechanism in the mast cell documents the presence of a functional Na+/K(+)
      pump in this cell. The pump activity is inhibited by lanthanides and by the
      divalent cations calcium, magnesium, barium and strontium. The pump has a large
      reserve capacity which probably is caused by a low intracellular concentration of
      sodium. This enables the pump to respond to changes in the intracellular sodium
      concentration. The inhibitory effect of di- and trivalent ions on the pump
      activity is probably a result of the inhibitory effect of these ions on the
      cellular sodium uptake. The digitalis glycosides, ouabain and digoxin, but not
      the more lipophilic drug digitoxigenin, increase both IgE-directed and non-IgE
      directed histamine release from the mast cell in a calcium-free medium, while
      there is no effect of digitalis glycosides in a medium containing physiologically
      relevant concentrations of calcium. The effect of digitalis glycosides on the
      histamine release is dependent on the drug concentrations used and the time of
      preincubation. An increase in the intracellular concentration of sodium secondary
      to inhibition of the Na+/K(+)-pump is the effector mechanism likely to explain
      the effect of digitalis glycosides on the mast cell histamine release. Increases
      in intracellular sodium might affect the intracellular concentration of calcium
      via changes in Na+/Ca(2+)-exchange. IgE-directed and non-IgE-directed stimulation
      of the mast cell activates the Na+/K(+)-pump. In case of compound 48/80-induced
      histamine release, the pump is stimulated for at least 2 hr. It is proposed, that
      the poststimulatory activation of the Na+/K(+)-pump is due to increased cellular
      sodium uptake associated with the release process. This sodium uptake may occur
      via Na+/Ca(2+)-exchange, Na+/H(+)-exchange, Na+/K+/2Cl(-)-cotransport or a non
      selective ion channel. Besides describing aspects of the function and regulation
      of the Na+/K(+)-pump in the rat peritoneal mast cells, this thesis points to the
      potential role of sodium transport mechanisms in mast cell physiology.
      Pharmacological manipulations of such transport mechanisms might in the future
      add to the treatment of allergic diseases.

PMID- 8747802
TI  - Basophil histamine release in allergic and non-allergic patient populations.
      Applications of a novel washed blood histamine release assay.

PMID- 8747803
TI  - Thiol compounds and organic nitrates.
AB  - Organic nitrates are widely used in the treatment of ischemic heart disease. The
      magnitude and duration of their circulatory and ischemic effects are, however,
      rapidly reduced during continuous treatment. The specific mechanisms underlying
      this tolerance development are not clear. According to the most widely accepted
      theory, tolerance is due to an intracellular depletion of thiol compounds (GSH
      and/or cysteine) involved in the conversion of nitrates to vasoactive
      intermediates. This presentation deals with aspects of in vivo thiol/nitrate
      interactions in different experimental and clinical conditions. The major results
      and conclusions are: The acute hypotensive effect of NTG is decreased by lowering
      of intracellular GSH levels. This finding emphasizes that normal intracellular
      thiol levels are required for optimal conversion of nitrates. Thus, intracellular
      GSH plays a critical role in the metabolism of NTG. Despite development of
      tolerance to the hypotensive effect of NTG, arterial and venous thiol levels are
      similar in nitrate tolerant and non-tolerant animals, suggesting that depletion
      of vascular thiol compounds may not be the cause of nitrate tolerance in vivo.
      The effect of exogenous thiol administration on intravascular thiol levels are
      different in nitrate tolerant and non-tolerant conscious rats. Exogenous thiol
      compounds (e.g. NAC) augments the hypotensive effect of NTG by a tolerance
      nonspecific mechanism. This effect is most likely mediated by an extracellular
      and/or membrane-related nitrate/thiol interaction and formation of NO. N
      acetylcysteine inhibits angiotensin converting enzyme and counteracts nitrate
      induced stimulation of the renin angiotensin system in vivo. Therefore, in
      addition to an effect on nitrate metabolism, thiol compounds may modify tolerance
      development by attenuating nitrate-induced counter-regulatory mechanisms. In the
      clinical setting, co-administration of NAC and ISDN delays and partially prevents
      tolerance to the antianginal and antiischemic effects normally seen in patients
      with stable angina pectoris during treatment with ISDN. N-acetylcysteine
      treatment in humans, potentiates and preserves nitrate induced venodilation and
      augments the effect of nitrates on small resistance vessels without affecting the
      response to nitrates in larger sized arteries. Thus, administration of NAC may
      change the normal vasodilator profile of nitrates. In conclusion, changes in
      cellular thiol levels may modify the hemodynamic effect of organic nitrates and
      the cellular handling of thiols and/or thiol related enzymes is altered after
      development of nitrate tolerance. In addition, a tolerance unrelated
      thiol/nitrate interaction, potentiating the effect of nitrates, may occur after
      administration of exogenous thiol compounds. In the clinical setting
      administration of thiols results in a characteristic change in the vasodilator
      profile of nitrates and an attenuation of the nitrate-induced stimulation of the
      renin-angiotensin system. The combination of these effects probably contributes
      to the improvement in antianginal and antiischemic parameters which may be seen
      during continuous and prolonged treatment with nitrates and thiol compounds.

PMID- 8747804
TI  - Failure to detect a general reduction of surgical wound infections in Danish
      hospitals.
AB  - The aim of this study was to see if introduction of continuous monitoring of the
      incidence of surgical wound infections would result in a reduction in the
      cumulated infection rates. Data from a Danish sentinel system, including more
      than 65,000 operations, are shown to be sufficiently representative to be used as
      the basis of a national surveillance system for surgical wound infections. The
      overall infection rates increased with age and with contamination of the wound.
      Antibiotic prophylaxis was used in 36% of the operations, with a higher fraction
      among elderly patients, and in contaminated or major operations. The length of
      stay was significantly and equally extended for patients with superficial or deep
      infections, compared to patients without wound infections. The results from 13
      departments could be followed at least two years from the beginning of the
      registration. No general preventive effects of the continuous monitoring were
      found in these surgical units.

PMID- 8747805
TI  - A clinical report on speech production of cochlear implant users.
AB  - OBJECTIVE: The aim was to assess articulation and speech intelligibility over
      time in a group of cochlear implant users implanted at 8 yr or over. The
      hypothesis was that the postoperative speech production performance would be
      greater than the preoperative performance. DESIGN: A test of intelligibility
      using sentences and an articulation test measuring non-imitative elicited speech
      were administered to 11 and 10 subjects, respectively, who were implanted with
      the 22-electrode cochlear implant. Nine subjects received both tests. Age at
      implantation ranged from 8 yr to 20 yr and implant use ranged from 1 yr to 4 yr 5
      mo. RESULTS: For both the intelligibility and articulation tests roughly half of
      the subjects showed significant improvements over time and group mean
      postoperative performance significantly exceeded preoperative performance.
      Improvements occurred for front, middle, and back consonants; for stops,
      fricatives, and glides and for voiceless and voiced consonants. CONCLUSIONS:
      Despite being deprived of acoustic speech information for many childhood years,
      roughly half of the patients assessed showed significant gains in speech
      intelligibility and articulation postimplantation. The lack of a control group of
      non-implanted patients means that we cannot separate out the influence of the
      implant on speech production from other influences such as training and tactile
      kinaesthetic feedback.

PMID- 8747806
TI  - Candidates for multiple frequency response characteristics.
AB  - This study examined what types of subjects may benefit from the use of multiple
      memory hearing aids that offer variation in their frequency response
      characteristics. Thirty subjects with varied degrees and configurations of
      hearing loss compared an individually prescribed frequency response (NAL) and two
      variations in which the real-ear response slope was either increased (more high
      frequency emphasis) or decreased by about 3 dB/octave over the range from 500 Hz
      to 4000 Hz. The evaluations consisted of paired comparison judgments of
      pleasantness and of ease of understanding speech, in quiet and in three
      background noises with substantially different acoustic spectra (traffic noise,
      speech babble, and high-frequency noise). Twelve of the 30 subjects selected
      different frequency responses for different background noises and/or for
      different response criteria. These subjects were characterized as having the more
      severe high-frequency hearing losses (averaged across 2000, 3000, and 4000 Hz).
      They also tended to be those for whom the three frequency responses provided the
      greatest variation in real-ear low-frequency gain. (Despite substantial
      electronic variations, some subjects received only small variations in real-ear
      gain at the low frequencies). When subjects chose a different response for
      different conditions, they tended to prefer responses for which the slope was
      negatively related to the spectrum of the stimulus. This was true for both
      response criteria. The conclusion is that hearing aid users with substantial high
      frequency losses, and who can be fitted with sufficient variation in the low
      frequency real-ear gain, have the potential to benefit from having a choice of
      frequency response characteristics.

PMID- 8747807
TI  - The relationship between listening conditions and alternative amplification
      schemes for multiple memory hearing aids.
AB  - OBJECTIVE: The aim of this study was to determine a relationship among selected
      listening conditions and amplification schemes that could be provided in a
      multiple memory hearing aid. DESIGN: The study consisted of three laboratory
      tests: 1) A screening test to select hearing impaired subjects who appeared to
      benefit from multiple amplification schemes. 2) A category scaling test to rank
      16 amplification schemes in 15 listening conditions. The 16 schemes were
      simulated with a digital master hearing aid and comprised 5 linear systems and 11
      compression characteristics. The 15 listening conditions comprised 6 listening
      environments combined with 2 or 3 response criteria. 3) A paired comparison test
      in which the two highest ranked amplification schemes were evaluated together
      with a reference linear frequency response (NAL) in a round-robin test. RESULTS:
      The screening test demonstrated that 21 hearing impaired people out of 25 with
      mild or moderate, flat or gently sloping hearing losses appeared to benefit from
      multiple amplification schemes. Age or audiometric factors did not serve to
      discriminate between those who selected different schemes and those who did not.
      In general, the NAL-response was preferred or was as good as any other for
      listening to speech in quiet, speech in reverberation, speech in babble-noise,
      and for naturalness of all listening environments. The subjects consistently
      selected an amplification scheme other than the NAL-response for four specific
      listening conditions. The findings suggest that substantial high-frequency
      compression is preferred for the ease of understanding multiple talkers, whose
      voices differ in overall level, in quiet environments. The annoyance of low
      frequency background noise can be reduced by low-frequency compression, whereas a
      frequency response steeper than the NAL-response makes it easier to understand
      speech in low frequency background noise. Finally, a frequency response flatter
      than the NAL-response can be used to make a high-frequency background noise sound
      less annoying. CONCLUSION: Hearing aid users with mild or moderate, flat or
      gently sloping hearing losses, fitted with equal and sufficient variation in
      amplification, prefer different amplification schemes depending on the number of
      talkers, the background noise and the response criterion.

PMID- 8747808
TI  - Comparison of two hearing aid receiver-amplifier combinations using sound quality
      judgments.
AB  - Sound quality judgments were obtained on two binaural pairs of laboratory hearing
      aids with similar battery drain. One pair had a traditional low-current-drain
      "starved Class A" output stage. The other had a new (at the time) "Class D"
      output stage. Speech and music reproduction was rated, for seven input levels
      between 70 and 100 dB SPL, on an overall quality scale by juries of normal
      hearing and hearing-impaired subjects. The same subjects also were asked to
      assign a dollar value to each condition by answering the question "What would you
      pay for a hearing aid that sounded like that?" Both subject groups rated the
      hearing aids with the Class D output stage as having superior sound quality
      across a variety of input levels and test materials, consistent with objective
      distortion measurements. On the average, each one-percentage point increase in
      sound quality rating corresponded to a $6.75 increase in perceived value in these
      experiments.

PMID- 8747809
TI  - Time-windowing of click-evoked otoacoustic emissions to increase signal-to-noise
      ratio.
AB  - OBJECTIVE: To investigate the effects of decreasing the response-window duration
      on the signal-to-noise ratio (S/N) of click-evoked otoacoustic emissions
      (CEOAEs). DESIGN: The ILO88 (Otodynamics, Ltd.) was used to measure CEOAEs from
      149 normal adult ears, and 75 adult ears with high-frequency sensorineural
      hearing loss. Data were collected using the default response window of 2.5 to
      20.5 msec post-click. Each response was rewindowed, post-hoc, from 2.5 to 7.5
      msec, 2.5 to 9 msec, 7.75 to 14.25 msec, and 13 to 19.5 msec post-click. For each
      window, spectra of the CEOAE and of the background noise were determined. The S/N
      was estimated by subtracting the noise level from the CEOAE amplitude. RESULTS:
      The 13- to 19.5-msec window contained little CEOAE energy relative to earlier
      windows. Relative to the 2.5- to 20.5-msec window, the 2.5- to 7.5- and 2.5- to 9
      msec windows reduced noise levels more than CEOAE amplitudes, yielding increased
      S/N, and greater "reproducibility" values. The increased S/N of the 2.5- to 7.5-
      and 2.5- to 9-msec windows allowed measurement of greater CEOAE-amplitude
      reductions in the impaired ears relative to the normal ears. With short-duration
      windows, click-presentation rate could be increased, allowing more responses to
      be averaged in a given time, thus further decreasing noise levels. Although click
      rate was not varied in the present study, the decrease of noise levels is
      predictable. Accounting for this factor, it is expected that a specified S/N
      would be obtained about five times faster using the 2.5- to 7.5-msec window with
      a 7.5-msec interstimulus interval, than when using the default window.
      CONCLUSIONS: Decreasing the response-window duration substantially increases the
      measurement efficiency of CEOAEs in adults, and thus may enhance clinical-test
      performance.

PMID- 8747810
TI  - Noise-induced otoacoustic emission loss with or without hearing loss.
AB  - The association between audiometric hearing thresholds and click-evoked
      otoacoustic emission (CEOAE) spectral properties was examined in 129 adult
      subjects with and without a noise-induced hearing loss (NIHL). Subjects were
      grouped according to their "beginning of hearing loss frequency" and their
      exposure to hazardous noise. Emissions were recorded with an ILO88 Otodynamic
      Analyzer (Version 2.9) used in the default mode. CEOAE levels decreased as the
      hearing threshold increased at each of the test frequencies (1,2,3, and 4 kHz).
      At frequencies where hearing thresholds were worse than 20 dB HL, CEOAEs could
      not be recorded. Thus as the "beginning of hearing loss frequency" decreased, the
      frequency range of the emissions became narrower. The hearing threshold for which
      emissions were not recorded varied significantly between subjects, such that even
      at frequencies where the hearing threshold was 0 dB HL emissions were not always
      observed. Noise-exposed, normal-hearing subjects had reduced overall CEOAE power
      with a narrow frequency range as compared with normal-hearing, nonexposed to
      noise subjects. For our test conditions, the presence of CEOAEs necessarily
      suggests hearing thresholds of 20 dB HL or less at the corresponding frequency. A
      lack of emissions does not necessarily indicate hearing thresholds beyond 20 dB
      HL.

PMID- 8747811
TI  - Input/output curves to tone bursts and clicks in extratympanic and transtympanic
      electrocochleography.
AB  - OBJECTIVE: The aim of this study is to explore the applicability of two specific
      methods in extratympanic (ET) electrocochleography that have rarely been used
      there, but are more commonly applied in transtympanic (TT) approaches. These two
      methods are the use of tone burst stimulation in addition to clicks, and the
      analysis of amplitude input/output curves as a measure of cochlear recruitment
      due to a pathological spread of excitation. DESIGN: Simultaneous extratympanic
      and transtympanic recordings were made in 30 patients with various types and
      degrees of cochlear hearing loss. ET recordings were also made in a group of
      normal subjects. Stimuli were tone bursts at octave frequencies from 500 to 8000
      Hz and clicks, at intensity levels of about 90 dB down to response threshold in
      10 dB steps. First, a general comparison is made of ET versus TT response
      properties, then the initial slopes of I/O curves in both sets of data are
      evaluated. RESULTS: ET responses are reduced in amplitude with respect to TT
      responses by a factor of 0.43 on average. Within each subject this factor is
      independent of stimulus type or level, but it has a substantial intersubject
      variation. ET and TT latencies are identical. From the normal data a criterion
      for abnormality of the slope of the I/O curve is derived in a similar way as
      available for TT data. Using this criterion ET I/O curves appear to be
      significantly steeper than normal in recruiting ears, albeit with a lesser
      sensitivity than for the associated TT data. CONCLUSIONS: Extratympanically
      recorded responses to tone burst stimuli provide basically the same information
      as transtympanic recordings. However, for a reliable interpretation of responses
      to low-intensity stimuli a larger amount of signal averaging is required. The
      analysis of I/O curves is a useful extension of current ET methods as a
      contribution to assessing a pathological spread of excitation in the cochlea.

PMID- 8747812
TI  - The auditory brain stem response in patients with brain stem or cochlear
      pathology.
AB  - OBJECTIVE: The purpose of this study was to determine the value, based on true
      positive and false-positive rates, of various auditory brain stem response (ABR)
      indices in discriminating patients with brain stem lesions from patients with
      cochlear lesions. DESIGN: A factorial design was used in this retrospective
      study. Receiver operating characteristics (ROC) curves were constructed to
      analyze the performance of 32 patients with brain stem lesions and 33 patients
      with cochlear involvement for the absolute latency of wave V; the I-III, III-V,
      and I-V interwave intervals; the interaural latency difference and the V/I
      amplitude ratio. Analyzed in the same manner were four combinations of ABR
      indices. RESULTS: Based on the ROC curves, the clinically most valuable index was
      the I-V interval, but overall the individual indices showed only moderate
      sensitivity to brain stem pathology. By combining several indices, the
      sensitivity to brain stem involvement was improved. However, as expected, the
      overall false-positive rate also increased. CONCLUSIONS: There is a diagnostic
      advantage to using more than one ABR index in evaluating patients suspected of
      having brain stem involvement.

PMID- 8747814
TI  - The articulatory basis of babbling.
AB  - This article evaluates the "Frames, then Content" hypothesis for speech
      acquisition, which states that much of the patterning of babbling is a direct
      result of production of syllabic "Frames" by means of rhythmic mandibular
      oscillation, with relatively little of the intrasyllabic and intersyllabic
      "Content" of the syllable-like cycles under mandible-independent control.
      Analysis was based on a phonetically transcribed corpus of 6,659 utterances of 6
      normally developing infants obtained from one-hour weekly audio-recordings over a
      4-6 month period. Intrasyllabic predictions were that front vowels would
      preferentially co-occur with front (alveolar) consonants, back vowels with back
      (velar) consonants, and central vowels with labial consonants, with the latter
      effect presumably resulting from mandibular oscillation alone. Intersyllabic
      predictions were for more variegation in tongue height for vowels than in front
      back tongue movement, and for consonant manner changes to predominate over place
      changes (related primarily to mandibular oscillation). All 30 individual
      predictions from both hypotheses were confirmed, leading to a conception of the
      articulatory basis of babbling as "Frame Dominance."

PMID- 8747813
TI  - Fundamental frequency, intensity, and vowel selection: effects on measures of
      phonatory stability.
AB  - Measures of phonatory stability such as jitter, shimmer, and signal-to-noise
      ratio (SNR) are increasingly used in clinics and laboratories, yet questions
      about the effects of various aspects of voice production on these acoustic
      variables have received only limited attention. The purpose of the present study
      was to examine the effects of frequency, intensity, and vowel selection on those
      measures of phonatory stability. Twenty-nine young adult females were used as
      subjects. Each subject produced vocalizations at her speaking fundamental
      frequency (SFF) and one octave above SFF; at 60, 70, and 80 dB; and on the vowels
      /i/ and /a/, for a total of 12 vocalizations per subject. These vocalizations
      were then analyzed, using CSpeech acoustic analysis software, to obtain measures
      of jitter, shimmer, and SNR. Results revealed that frequency, intensity, and
      vowel selection all affected various phonatory stability measures, with the
      highest perturbation values almost always occurring in the low frequency-low
      intensity condition. Implications and physiological explanations for the results
      of the study were presented.

PMID- 8747815
TI  - Comparisons among aerodynamic, electroglottographic, and acoustic spectral
      measures of female voice.
AB  - This study examines measures of the glottal airflow waveform, the
      electroglottographic signal (EGG), amplitude differences between peaks in the
      acoustic spectrum, and observations of the spectral energy content of the third
      formant (F3), in terms of how they relate to one another. Twenty females with
      normal voices served as subjects. Both group and individual data were studied.
      Measurements were made for the vowel in two speech tasks: strings of the syllable
      /pae/and sustained phonation of /ae/, which were produced at two levels of vocal
      effort: comfortable and loud voice. The main results were: 1. Significant
      differences in parameter values between /pae/and/ae/were related to significant
      differences in the sound pressure level (SPL). 2. An "adduction quotient,"
      measured from the glottal waveform at a 30% criterion, was sensitive enough to
      differentiate between waveforms reflecting abrupt versus gradual vocal fold
      closing movements. 3. DC flow showed weak or nonsignificant relationships with
      acoustic measures. 4. The spectral content in the third formant (F3) in
      comfortable loudness typically consisted of a mix of noise and harmonic energy.
      In loud voice, the F3 spectral content typically consisted of harmonic energy. 5.
      Significant differences were found in all measures between tokens with F3
      harmonic energy and tokens with F3 noise, independent of loudness condition. 6.
      Strong relationships between flow- and EGG-adduction quotients suggested that
      these signals can be used to complement each other. 7. The amplitude difference
      between spectral peaks of the first and third formant (F1-F3) was found to add
      information about abruptness of airflow decrease (flow declination) that may be
      lost in the glottal waveform signal due to low-pass filtering. The results are
      discussed in terms of how an integrated use of these measures can contribute to a
      better understanding of the normal vocal mechanism and help to improve methods
      for evaluating vocal function.

PMID- 8747816
TI  - Factor analysis of proficient esophageal speech: toward a multidimensional model.
AB  - This study identified acoustic patterns in the speech samples of 26 esophageal
      speakers judged by experienced listeners to be highly proficient and
      intelligible. Tape-recorded readings were acoustically analyzed in terms of
      frequency, intensity, and duration variables. Application of two multidimensional
      statistical procedures, factor analysis and cluster analysis, revealed four
      distinctive acoustic profiles that captured all 26 subjects. The multidimensional
      model derived from these profiles maintains important individual differences in
      alaryngeal speech style.

PMID- 8747817
TI  - Comparison of two forms of intensive speech treatment for Parkinson disease.
AB  - This study investigated the effect of two forms of intensive speech treatment,
      (a) respiration (R) and (b) voice and respiration (Lee Silverman Voice Treatment
      [LSVT]), on the speech and voice deficits associated with idiopathic Parkinson
      disease. Forty-five subjects with Idiopathic Parkinson disease completed
      extensive pretreatment neurological, otolaryngological, neuropsychological, and
      speech assessments. All subjects completed 16 sessions of intensive speech
      treatment, 4 times a week for 1 month. Pre- and post-treatment measures included
      intensity and maximum duration during sustained vowel phonation. Intensity,
      habitual fundamental frequency, fundamental frequency variability, and utterance
      and pause duration were measured during reading of the "Rainbow Passage" and
      conversational monologue as well. Family and subject self-ratings were completed
      pre- and post-treatment for the perceptual variables loudness, monotonicity,
      hoarseness, overall intelligibility, and initiation of conversation. Significant
      pre- to post-treatment improvements were observed for more variables and were of
      greater magnitude for the subjects who received the voice and respiration
      treatment (LSVT). Only subjects who received the LSVT rated a significant
      decrease post-treatment on the impact of Parkinson disease on their
      communication. Correlations between descriptive prognostic variables (i.e., stage
      of disease, speech/voice severity rating, depression, and time since diagnosis)
      and magnitude of treatment-related change indicated these factors did not
      significantly predict treatment effectiveness. These findings suggest that
      intensive voice and respiration (LSVT) treatment, focusing on increased vocal
      fold adduction and respiration, is more effective than respiration (R) treatment
      alone for improving vocal intensity and decreasing the impact of Parkinson
      disease on communication.

PMID- 8747818
TI  - Kinematic analysis of lower lip movements in ataxic dysarthria.
AB  - The present study investigates the influence of cerebellar disorders on
      articulatory performance. A linear trend between peak velocity and movement
      amplitude seems to represent a basic organizational principle both of upper limb
      and speech motor control. This relationship is preserved in arm movements of
      patients with cerebellar dysfunction. However, these subjects show a decreased
      slope of the respective regression lines under the instruction to perform
      movements as fast as possible. In order to find out whether these findings also
      hold for speech motor control, peak velocity, range, and duration both of the
      opening and closing gestures during production of /pap/- as well as /pa:p/
      sequences-embedded into a carrier phrase each-were measured using an optoelectric
      system. In addition, vowel length (/a/, /a:/) was determined at the acoustic
      speech signal: (a) The cerebellar patients showed a prolongation of both vowel
      targets. Most of them, nevertheless, presented with discernible durational
      contrasts; (b) The articulatory gestures were characterized by a highly linear
      relationship between peak velocity and movement range in the cerebellar as well
      as in the control group; (c) As a rule, the cerebellar subjects had decreased
      velocity-displacement ratios as compared to the normals; (d) The discrepancy in
      slope of the computed regression lines between the controls and the patients
      varied according to the type of movement (opening vs. closing gesture) and-to a
      lesser decree-linguistic demands (short vs. long vowel). These data indicate an
      impaired ability of cerebellar patients to increase muscular forces in order to
      produce adequately scaled articulatory gestures of short duration.

PMID- 8747819
TI  - Required number of tokens to determine representative voice perturbation values.
AB  - Acoustic perturbation analyses of prolonged vowels are used in determining
      phonatory stability characteristics. When a number of tokens are analyzed, the
      average perturbation values create a stability profile of the voice. How many
      tokens are needed to obtain a representative perturbation value? In this study,
      five perturbation measures were considered, namely, jitter, shimmer, harmonics-to
      noise ratio, coefficient of variation for amplitude, and coefficient of variation
      for frequency. Subject groups were chosen on the basis of individual average
      perturbation values. Results indicate that, except for the harmonics-to-noise
      ratio, generally, the less stable the voice, the greater is the number of tokens
      needed to obtain representative averages. For highly stable voices, at least six
      tokens are suggested: for voices with normal to high levels of instability, at
      least 15 tokens are recommended. Regardless of vocal stability, at least 10
      tokens are suggested for the harmonics-to-noise ratio measure.

PMID- 8747820
TI  - Functional categories in the grammars of children with specific language
      impairment.
AB  - Children with specific language impairment often show a serious limitation in
      their use of grammatical morphemes such as verb inflections and free-standing
      closed-class forms. The purpose of this study was to determine whether such
      difficulty constitutes a problem with entire functional categories. Examination
      of the spontaneous speech of a group of 10 English-speaking children with
      specific language impairment revealed clear evidence of each of the functional
      categories examined: Determiner, inflection, and Complementizer. However,
      relative to younger normally developing children with comparable mean utterance
      lengths, these children showed lower percentages of use of many of the
      grammatical elements associated with these functional categories. The utility of
      employing a functional category framework in the study of specific language
      impairment and the implications of the findings for other accounts of this
      disorder are discussed.

PMID- 8747821
TI  - Transparency of one-handed Amer-Ind hand signals to nonfamiliar viewers.
AB  - Thirty non-brain-damaged adults viewed 104 videotaped Amer-Ind hand signals. The
      majority of these hand signals were produced with one hand; 60 originally one
      handed gestures and 31 left-hand adaptations of two-handed gestures were included
      in the data analyses. Nineteen subjects were between the ages of 20 and 30 years
      (younger group), and 11 subjects were between the ages of 50 and 69 years (older
      group). After viewing each hand signal twice in succession, the subjects wrote at
      least one word for that signal's meaning. The mean percentage of one-handed
      signals correctly identified was 48.2%; these signals varied widely in
      transparency (0% to 100%). The left-hand adaptations were significantly lower in
      transparency than the originally one-handed signals. The younger and older
      subjects did not differ in the mean percentage of one-handed signals they
      identified correctly (49.0% and 46.4%, respectively). However, some individual
      hand signals were easier for the younger subjects to identify; the opposite was
      also true.

PMID- 8747822
TI  - Contingency and breakdown: children with SLI and their conversations with mothers
      and fathers.
AB  - The present study aimed to investigate the nature and frequency of parental
      recasts (both mothers and fathers) to children with SLI as compared to normal
      language learning children of the same language stage including their younger
      siblings. The comparisons were made within the framework of discourse function to
      include behaviors related to conversational contingency and conversational
      breakdown. Results showed that children with SLI at the early stages of
      development experience a simple recast gap in their linguistic input. Qualitative
      differences in the context in which recasts occurred were also noted.
      Furthermore, some differences between mothers and fathers were found. These
      findings are discussed in light of previous research with particular reference to
      the Rare Event Theory and the Bridge Hypothesis.

PMID- 8747823
TI  - Effects of prenatal exposure to cocaine and associated risk factors on language
      development.
AB  - During the past decade there has been a dramatic increase in the number of
      children born with prenatal exposure to cocaine. However, there is very little
      hard data concerning the later development of these children. The purpose of this
      preliminary study was to compare the language development profiles of 5 children
      prenatally exposed to cocaine and associated risk factors to the language
      development profiles of a matched non-exposed control group in terms of analyses
      of the discourse-pragmatic, semantic, and form components of language. The
      language evaluation was based on the analysis of a 30-minute language sample. The
      results suggested differences between the two groups as well as differences
      within the cocaine-exposed group. The major differences between the two groups
      were in discourse-pragmatics although less marked differences in syntactic
      development were also found. The results are discussed in relation to the
      potential contribution of pertinent medical and environmental risk factors. The
      study suggests that for children with prenatal exposure to cocaine in combination
      with multiple associated risk factors, language development may be compromised.

PMID- 8747824
TI  - Redirects: a strategy to increase peer initiations.
AB  - Preschoolers' verbal abilities influence their verbal interactions with play
      partners. Previous research has suggested that preschoolers with specific
      language impairment (SLI) are more likely to initiate conversations with adults
      than with peers, as compared to their typically developing peers. This study
      investigated a teacher-implemented procedure, redirects, as a means to facilitate
      initiations to peers. A redirect occurs when a child initiates to the teacher,
      and the teacher then suggests the child initiate to a peer, thereby redirecting
      the child from an adult to a peer. Four preschool boys with SLI participated in
      the study. The teacher training was successful in increasing the teacher's
      ability to redirect the children's initiations. The children consistently
      responded to redirects by initiating to peers, and most redirected initiations
      received conversational responses from peers. Generalization effects to
      spontaneous peer initiations following the intervention period were demonstrated
      for 2 of the boys.

PMID- 8747825
TI  - Initiation and repair of intentional communication acts by adults with severe to
      profound cognitive disabilities.
AB  - This study assessed the communication initiation and repair behaviors of 28
      individuals with severe to profound mental retardation in a variety of
      experimental conditions. All of these individuals communicated through
      nonsymbolic gestures. The experimental procedures were devised to simulate the
      conditions that typically evoke two different types of initiations: comments and
      requests. Each subject initiation was followed by an experimenter response that
      indicated a communication breakdown to determine if and how these subjects would
      attempt to repair such breakdowns. Different indicators of communication
      breakdown were systematically varied in these scripted interactions, including
      explicit requests for repair (verbal and gestural) and implicit requests for
      repair (failure to respond or inappropriate response to the subject's
      communication act). All subjects initiated at least one communication act, and
      all but three subjects repaired at least one communication act following a
      breakdown. Significantly more subjects initiated protoimperative than
      protodeclarative communication acts, despite equal opportunities for both types
      of acts. Across all conditions, additions were observed to occur significantly
      less often than recasts or repetitions. There were no significant differences in
      the number of subjects repairing communication following the different types of
      communication breakdown.

PMID- 8747826
TI  - Measuring children's lexical diversity: differentiating typical and impaired
      language learners.
AB  - This study evaluated the extent to which measures of lexical diversity (type
      token ratio and number of different words produced) differentiated children with
      specific language impairment (SLI) from children whose language skills were
      following typical developmental expectations. Analysis of 50- and 100-utterance
      samples revealed that children with SLI did not significantly differ from their
      age- and language-equivalent peers on type-token ratio; however, children with
      SLI did use significantly fewer different words than their age-equivalent peers
      in these samples. When samples of 100 and 200 tokens were considered, the
      children with SLI also used significantly fewer different words than their age
      equivalent counterparts. Overall, the findings of this study discourage the use
      of type-token ratio, as traditionally calculated, in many clinical and research
      activities related to children with SLI. In contrast, the number of different
      words produced provides a more sensitive and informative estimate of lexical
      diversity.

PMID- 8747827
TI  - Effects of picture size and placement on memory for written words.
AB  - A study investigating the effects of varying size and position of line drawings
      in combination with written words was conducted with kindergarten students.
      Subjects were shown written words under four conditions that represented various
      size and position relationships between line drawings and orthography. After 4
      consecutive days of exposure in an incidental learning task, both identification
      and recognition measures were obtained. Results showed superior performance for
      word-only and enhanced-word conditions, over those in which small and large line
      drawings were paired with written words, supporting similar research findings
      conducted with reading tasks. Implications are drawn for application to
      individuals with little or no functional speech who use graphic symbols for
      expressive communication.

PMID- 8747828
TI  - Verbal auditory closure and the speech perception in noise (SPIN) Test.
AB  - Ability to utilize auditory contextual information to facilitate speech
      recognition verbal auditory closure is postulated to be a specific factor or
      primary mental ability, separable from general intelligence or other mental
      functions. This paper proposes that measurement of verbal auditory closure
      provides useful clinical information. Because the Speech Perception in Noise
      (SPIN). Test allows separate scores for understanding of sentences that contain
      contextual information and of those that do not, the SPIN Test provides a good
      measure of verbal auditory closure. Now that an authorized version of the revised
      SPIN Test is commercially available, it is appropriate to review published
      information about reported performance of different listener groups on this
      instrument and to propose additional research questions that deserve
      investigation.

PMID- 8747829
TI  - Priming the visual recognition of spoken words.
AB  - A preliminary investigation was conducted to understand the effects of word
      visibility and prime association factors on visual spoken word recognition in
      lipreading, using a related/ unrelated prime-target paradigm. Prime-target
      pairings were determined on the basis of paper-and-pencil word associations
      completed by 85 participants with normal hearing. Spoken targets included 60
      single-syllable Modified Rhyme Test words, prerecorded on laser video disc.
      Participants included 20 individuals with normal hearing and at least average
      lipreading skill for sentence-length materials. In related prime-target pairings,
      more targets with a high prime association were identified than with a low prime
      association. In unrelated prime-target pairings, a larger number of more-visible
      than less-visible targets was correctly identified. Individual participant
      differences were not statistically significant. Results from the present study
      suggest implications for models of visual spoken word recognition.

PMID- 8747830
TI  - Visual word recognition in two facial motion conditions: full-face versus lips
      plus-mandible.
AB  - The present study used a new method to develop video sequences that limited
      exposure of facial movement. A repeated-measures design was used to investigate
      the visual recognition of 60 monosyllabic spoken words, presented in an open set
      format, for two face exposure conditions (full-face vs. lips-plus-mandible).
      Twenty-six normal hearing college students and 4 adults with bilateral
      sensorineural hearing loss speechread a video laserdisc presentation of a male
      talker under the two face exposure conditions. Percent phoneme correct scores
      were similar in the part-face and full-face conditions. However, scores
      significantly improved for the repeated measure independent of the face exposure
      condition observed. The results suggested that speechreaders (a) can recognize
      monosyllabic words in video sequences that provide information only about
      movements of the lips-plus-mandible region and (b) are sensitive to practice
      effects.

PMID- 8747831
TI  - The aging thyroid.

PMID- 8747832
TI  - Fat cell alpha 2-adrenoceptors: the regulation of fat cell function and
      lipolysis.

PMID- 8747833
TI  - Estrogen, progesterone, and vascular reactivity: potential cellular mechanisms.

PMID- 8747834
TI  - Extracellular calcium sensitivity and voltage-dependent calcium channels in C
      cells.
AB  - An essential function of C cells is to monitor [Ca2+]e and to increase CT
      secretion in response to small increments in [Ca2+]e. CT, in turn, decreases
      [Ca2+]e via its effects on bone and kidney. [Ca2+]e-dependent CT secretion is
      known to be mediated by corresponding changes in [Ca2+]i. The [Ca2+]e-sensing of
      C cells is mediated by DHP-sensitive, voltage-dependent Ca2+ channels, which
      allow Ca2+ influx even at the resting membrane potential. An increase of [Ca2+]e
      stimulates transmembrane Ca2+ influx via DHP-sensitive Ca2+ channels, thereby
      increasing [Ca2+]i and consequently CT secretion. Moreover, [Ca2+]e and cAMP
      dependent oscillations of [Ca2+]i are observed in C cells. Various neuropeptides
      and hormones involved in the control of CT secretion act by regulating Ca2+
      channel activity via G proteins. One of these endogenous modulators is SS, which
      is produced by the C cells themselves and tonically inhibits CT secretion by
      inhibiting voltage-dependent Ca2+ channels.

PMID- 8747835
TI  - Follicle-stimulating isohormones: characterization and physiological relevance.

PMID- 8747836
TI  - Mitochondria, magnesium and migraine.
AB  - The evidence for disordered mitochondrial oxidative phosphorylation and reduced
      intracellular free magnesium in brain and body tissue of migraine suffers both
      between and during an attack is reviewed. We propose that between attacks these
      metabolic shifts cause instability of neuronal function which enhances the
      susceptibility of brain to develop a migraine attack.

PMID- 8747837
TI  - Cerebral arterial fat embolism in the rabbit.
AB  - This study was designed to measure the effects of cerebral arterial fat embolism
      on cerebral blood flow and function. Rabbits were injected via the left internal
      carotid artery with the neutral triglyceride triolein. Left cerebral blood flow
      was measured by laser Doppler flowmetry, and left sided brain function by
      electrocorticogram and cortical somatosensory evoked responses following
      electrical stimulation of the forepaw. Readings were taken for 2 h before
      injection to establish a baseline, and for 3 h after injection. Cerebral blood
      flow was significantly decreased at 45 min after the injection of the lipid, then
      progressively decreased further to approximately 50% of baseline after 2 h, at
      which level it remained for the last hour of the experiment. The
      electrocorticogram was rapidly, but transiently, suppressed. The evoked responses
      did not differ from baseline at each of the time points measured. Using 125I
      triolein, 2.49% of the injected dose was measured in the brain 3 min after
      injection. The results show that in this rabbit model of cerebral arterial fat
      embolism only a small percentage of injected lipid passes into the brain, but
      this is sufficient to cause a reduction in cerebral blood flow over the following
      2 h. The evoked responses never alter significantly from baseline values.

PMID- 8747838
TI  - CNQX prevents spinal motor neuron death following sciatic nerve transection in
      newborn rats.
AB  - A rapid and reproducible spinal motor neuron death occurs after sciatic nerve
      transection in neonatal rats. This neuronal death could be due to lack of
      retrogradely transported target derived neurotrophic factors, such as ciliary
      neurotrophic factor, brain-derived neurotrophic factor, leukemia inhibitory
      factor and glial cell line-derived neurotrophic factor. Another hypothesis
      suggests that glutamate and its receptors has been implicated as possible
      mechanism for motor neuron death. In order to investigate the effect of N-methyl
      D-aspartate (NMDA) and non-NMDA receptor antagonists on axotomy-induced cell
      death in the spinal motor neurons of neonatal rats, we have studied
      neuroprotective effects of these receptor antagonists. Newborn rats were
      anesthetized with hypothermia. Sciatic nerve was transected near the obturator
      tendon in the left thigh. Animals were then treated daily with MK-801, APV, and
      CNQX for 14 days with intraperitoneal injections. Control animals received PBS in
      the same fashion. After the treatment, the number of spinal motor neurons in the
      L4-6 was counted. MK-801 and APV did not show any significant neuroprotective
      effect. By contrast, the number of surviving motor neurons was greater in animals
      that were treated with 1.0, 2.0 and 4.0 mg/kg of CNQX. This neuroprotective
      effect was not dose-related. We demonstrate that neuroprotective effect of CNQX
      on axotomized motor neurons, raises a possibility that such a agent may have
      therapeutic potential in motor neuronopathy and amyotrophic lateral sclerosis.

PMID- 8747839
TI  - Reactions of astrocytes and microglial cells around hematogenous metastases of
      the human brain. Expression of endothelin-like immunoreactivity in reactive
      astrocytes and activation of microglial cells.
AB  - An immunohistochemical study was made on the peritumoral gliosis which is
      produced around hematogenous metastases of the human brain. The material was
      derived from 73 autopsy cases with different primary malignancies and six control
      cases without evidence of brain disease. Reactive astrocytes of hypertrophic and
      gemistocytic types were present around and within all the metastases. Eighty-five
      percent of the cases with metastases showed expression of endothelin-like
      immunoreactivity in the peritumoral astrocytes. Such immunoreactive astrocytes
      were not present in the normal controls but have previously been found in
      reactive astrocytes around infarcts, lacunas, inflammatory and degenerative brain
      diseases. The endothelin-like immunoreactivity probably reflects an increased
      intracellular content of endothelin. If this peptide is released from the
      reactive astrocytes it may act as a mitogen and influence microcirculation by
      inducing vasoconstriction. Activation of microglial cells, detected by ferritin
      immunohistochemistry, was another frequent and widespread glial cell alteration
      around the metastases. In conclusion, the reactive gliosis, which is formed
      around metastases involves activated astrocytes as well as activated microglial
      cells. Both cell types can release numerous biologically active compounds which
      may influence the structure and function of the brain tissue around the
      metastases.

PMID- 8747840
TI  - Incidence and effects of increased cerebral blood flow velocity after severe head
      injury: a transcranial Doppler ultrasound study I. Prediction of post-traumatic
      vasospasm and hyperemia.
AB  - Cerebral blood flow velocity was monitored in 50 patients with severe head injury
      (GCS 8 or less) within 24 h of injury and at least once daily thereafter, using
      transcranial Doppler ultrasonography (TCD). Delayed post-traumatic vasospasm
      occurred in 20, and cerebral hyperemia in another 15. Doppler velocities were
      higher in vasospasm, which also lasted significantly longer than hyperemia. The
      presence of visible blood on an early CT scan was of some value in predicting
      vasospasm only (accuracy 59%). Xenon-133 cerebral blood flow (CBF) was also
      measured within 24 h of injury. An abnormal early cerebral blood flow level,
      either above or below a narrow central range, was more effective than CT in
      predicting vasospasm or hyperemia (accuracy 80%), while the combination of an
      abnormal blood flow and hemorrhagic findings on CT scan helped to determine which
      of these would occur later. Patients with an abnormal early cerebral blood flow
      and hemorrhagic findings on CT were more likely to develop vasospasm--accuracy
      for prediction of vasospasm 73%. This distinction may be of great importance,
      since these different groups of patients may well need different management.

PMID- 8747841
TI  - Incidence and effects of increased cerebral blood flow velocity after severe head
      injury: a transcranial Doppler ultrasound study II. Effect of vasospasm and
      hyperemia on outcome.
AB  - Cerebral blood flow velocities were measured in 50 severely head injured (Glasgow
      Coma Scale (GCS) 8 or less) patients using transcranial Doppler ultrasonography
      (TCD). Abnormally high TCD velocities were recorded in 35 patients; in 20 this
      was deemed to be due to vasospasm and in the other 15 to hyperemia. Patients who
      developed hyperemia also had the highest intracranial pressure (ICP) and the
      lowest cerebral perfusion pressure (CPP) of the three groups. Outcome was
      assessed at six months after injury using the Glasgow outcome scale and the
      disability rating scale. In the normal velocity group 87% of patients had a good
      outcome, compared with 47% of those with hyperemia and 40% of those with
      vasospasm. The highest velocity (HVEL), GCS, age, ICP and CPP were entered into a
      logistic regression analysis. HVEL, age and CPP were found to be the most
      significant predictors of outcome (chi 2 = 29.5; p < 0.0001). These factors
      predicted outcome with 82% accuracy, 86% sensitivity and 76% specificity. Routine
      monitoring of TCD velocity may be useful in detecting hyperemia and vasospasm
      after severe head injury, allowing appropriate treatment to be started as early
      as possible.

PMID- 8747842
TI  - Electroencephalography in lacunar infarction.
AB  - To determine the occurrence and clinical implications of electroencephalographic
      (EEG) abnormalities in patients with acute lacunar infarction, we conducted a
      single-blinded EEG study in 55 patients. Twenty-nine (53%) had mild EEG
      abnormalities, which were focal and ipsilateral to the side of infarction in 7
      patients (13%). Abnormalities were more common in patients with evidence of a
      prior stroke (10 of 12 patients, 83%). However, 43% (16 of 37 patients) of those
      without historical or radiologic evidence of a prior stroke also had mild EEG
      abnormalities. This represents a higher incidence of routine EEG abnormalities in
      lacunar infarction than is generally assumed. Indeed, these findings are more
      consistent with recent quantitative EEG studies that consistently have shown high
      rates of abnormalities in lacunar infarction. We did not find major EEG
      abnormalities, such as continuous or nearly continuous focal delta activity, in
      any patient with first lacunar infarction. We conclude that within the first 48 h
      after a first ischemic infarction, when computed tomography often fails to show
      abnormalities, an EEG that shows lateralized major abnormalities is useful in
      excluding the diagnosis of either lacunar infarction or infarction limited to the
      brain stem. Mild abnormalities occur more often than previously thought in
      lacunar infarction and do not exclude this diagnosis.

PMID- 8747843
TI  - Superoxide dismutase and free radicals in sporadic amyotrophic lateral sclerosis:
      relationship to clinical data.
AB  - We studied the relationships between the superoxide dismutase (SOD) activity,
      free radical (FR) levels and clinical data in patients with sporadic amyotrophic
      lateral sclerosis (SALS). The SOD activities and blood FR levels of 16 patients
      with SALS (mean age 58.6 +/- 10.2 years), 11 with other neurological disease,
      including myotonic dystrophy (ND, mean age 53.5 +/- 9.1 years), and 15 normal
      control subjects (mean age 56.2 +/- 7.3 years) were measured. The mean levels of
      FR in blood from the patients with SALS and ND and the SOD activities in red
      blood cells (RBC) from those with ND were significantly higher than the
      corresponding control values. There was a positive correlation between the SOD
      activities in RBC and blood hydroxyl radical levels in the patients with ND, but
      neither the patients with SALS nor the controls showed such a correlation. The
      SALS patients without pyramidal signs showed slow disease progression and their
      mean RBC SOD activity was significantly higher than the corresponding control
      value. We compared the FR levels and SOD activities of 8 patients who needed a
      respirator within 40 months after the onset of SALS (SALS40, mean age 58.7 +/-
      9.4 years), 3 who needed a respirator over 100 months after the onset of SALS
      (SALS100, mean age 58.3 +/- 15.9 years) and the controls. The mean blood FR
      levels of the SALS40 and SALS100 patients were significantly higher than the
      corresponding control values. The mean SOD activity in RBC from the SALS100 group
      was significantly higher than the SALS40 and control group values. Therefore, we
      concluded that elevated blood FR levels do not induce RBC SOD in SALS patients
      and that the disease progressed more rapidly in SALS patients with low than high
      RBS SOD activities.

PMID- 8747844
TI  - Increased sympathetic outflow to muscles in patients with amyotrophic lateral
      sclerosis: a comparison with other neuromuscular patients.
AB  - We investigated the effects of muscle loss and limitation of daily activities on
      sympathetic outflow to muscles by measuring muscle sympathetic nerve activity
      (MSNA) in 12 patients with amyotrophic lateral sclerosis (ALS) as compared with
      other 15 neuromuscular patients (controls). The burst incidence of MSNA at rest
      was significantly higher in patients with ALS, even in elderly patients, compared
      with controls (p < 0.01). There were no differences in the level of disability,
      heart rate or blood pressure at rest between two groups. Blood pressure and MSNA
      were less changed by head-up tilting in patients with ALS compared with controls.
      MSNA of ALS was not correlated with the disability score, PaO2, PaCO2, forced
      vital capacity, the disease duration or prognosis. MSNA at rest was increased in
      ALS patients, regardless of the severity of muscle loss or disability. It might
      be suggested that autonomic motor neurons seem to become affected by the same
      pathologic process that kills motor neurons.

PMID- 8747845
TI  - Mortality from motor neuron disease in Japan, 1950-1990: association with
      radioactive fallout from atmospheric weapons testing.
AB  - Motor neuron disease (MND) is a progressive and invariably fatal disease
      affecting the nuclei of the pyramidal tract and anterior horn cells. Despite
      intensive research into environmental agents associated with the onset or course
      of the disease, there is no single factor that can be confidently linked over
      time with regional, national or international variations in mortality rates.
      However, unusual variations in MND mortality rate in Japan from 1950-1990 were
      found to correlate highly significantly with variations in radioactive fallout
      released by atmospheric weapons testing in the Pacific. This association could be
      explained by the ingestion of alpha-emitting radionuclides acting upon a pre
      existing susceptible subpopulation, a hypothesis which is consistent with recent
      research on the epidemiology and pathology of MND. However, it is likely that
      radiation is only one of many factors that act singly or in combination to
      accelerate the condition in subpopulations susceptible to MND.

PMID- 8747846
TI  - Motor evoked potential changes in ischaemic stroke depend on stroke location.
AB  - This study was undertaken to evaluate the central motor conduction in ischaemic
      stroke and their role in predicting the short term prognosis. Fifty-six patients
      with CT proven infarction were examined after a mean duration of 9 (range 1-30)
      days. Patients' mean age was 54.6 years (range 22-80) and 44 of them were males.
      Motor evoked potentials (MEPs) on cortical stimulation were unrecordable in 57%
      and central motor conduction time (CMCT) was prolonged in 21% patients. Central
      motor conduction time was significantly related to the mortoricity index and
      outcome of the patients, but not to the size of infarction. The involvement of
      the primary motor area or its connection seemed to be an important determinant of
      the motor dysfunction, MEP abnormalities and outcome. A recordable MEP on
      cortical stimulation predicted a better outcome than an unrecordable one. Changes
      in central motor conduction occurred in 14 out of 33 patients who were followed
      up for a mean duration of 5.7 months (range 3-15). Improvement in CMCT was noted
      after 4 weeks in two patients, 5-12 weeks in eight, and after 12 weeks in four
      patients, highlighting the multiplicity of factors responsible for the recovery.

PMID- 8747847
TI  - Parvocellular and magnocellular contributions to visual evoked potentials in
      humans: stimulation with chromatic and achromatic gratings and apparent motion.
AB  - Psychophysical evidence suggests that two major parallel pathways, the
      parvocellular (P) and the magnocellular (M) pathways, exist in humans. We herein
      report that responses specific to the P and M systems can be recorded in human
      visual evoked potentials (VEPs) by using the appropriate stimuli. The onset of
      isoluminant chromatic (red-green) and high contrast achromatic sinusoidal
      gratings were used for stimulating the P-system. A chromatic stimulation evoked a
      characteristic negative wave (N1) with peak latencies around 120 msec. The
      amplitude showed an inverse U-shaped function as a function of spatial frequency
      with a peak at 2 c/deg. In contrast, VEPs to achromatic (black-white) gratings
      showed different spatial frequency characteristics with a peak at 5.3 c/deg. By
      varying the luminous intensity ratio between the red and green gratings, N1 was
      found to reach a maximum during isoluminant stimulation. An apparent motion
      display was used for stimulating the M-system. The speed of alternation (i.e.,
      the interstimulus interval (ISI)) was varied to record both the transient and
      steady-state VEPs. Transient VEPs showed triphasic waves with the major positive
      peak (P1) at around 120 ms. Steady-state VEPs were quasi-sinusoidal waveforms,
      depending on the ISI, and were quite stable across all subjects. There was a also
      high correlation between the motion threshold and the VEP amplitude. The above
      observations indicate that characteristic potentials may distinguish between
      these two parallel visual systems in humans. Thus, the combined use of
      isoluminant color and high contrast achromatic gratings and an apparent motion
      display is considered to be useful for evaluating both systems
      electrophysiologically.

PMID- 8747848
TI  - Brain MRI findings and cognitive impairment in patients undergoing chronic
      hemodialysis treatment.
AB  - Although both morphologic cerebral damage and cognitive dysfunction are known to
      occur in patients on chronic hemodialysis (CHD) their extent and possible
      relation have been rarely studied. We therefore performed magnetic resonance
      imaging of the brain and neuropsychological testing in 30 consecutive CHD
      patients (mean age 58 years; range 37-69) and in an equal number of asymptomatic
      volunteers matched for age, sex and major cerebrovascular risk factors. Twenty
      four (80%) of the CHD patients were demented according to the criteria of the
      Diagnostic and Statistical Manual of Mental Disorders IIIR and their mean scores
      on the Mini Mental State Examination (22.9 +/- 4 vs. 27.9 +/- 1.4; p < 0.001) and
      Mattis Dementia Rating Scale (112.3 +/- 21.5 vs. 141.9 +/- 2.3); p < 0.001) were
      significantly lower than those of controls. The brains of CHD patients showed
      significantly more atrophy on visual rating and semiquantitative morphometric
      measures. Multiple lacunes or confluent white matter hyperintensities
      predominated in 10 (33%) patients, three showed territorial infarcts and two a
      combination of both. Clinically these findings were unexpected in almost half of
      individuals. Marked cognitive impairment was associated with more extensive
      enlargement of the third ventricle (5.8 +/- 1.8 vs. 7.3 +/- 2 mm; p < 0.04) and
      the temporal horns (3.5 +/- 1.6 vs. 5.1 +/- 1.8 mm; p < 0.02) but not with the
      presence of cerebral ischemic lesions or any difference in laboratory data. These
      results call attention to a very high rate of cerebral damage in individuals
      undergoing CHD and suggest brain degeneration of probably toxic-metabolic
      etiology to be associated with severe cognitive impairment of these patients.

PMID- 8747849
TI  - Visual evoked potentials N75 and P100 latencies correlate with urinary delta
      aminolevulinic acid, suggesting gamma-aminobutyric acid involvement in their
      generation.
AB  - Pattern reversal visual evoked potentials were recorded from 31 subjects who were
      occupationally exposed to lead and 54 non-exposed controls. No significant
      effects of lead were observed in the general subject population. However, when
      only non-smokers (17 lead-exposed and 27 controls) were evaluated, significant
      effects were found. The P100, but not the N75, latency was significantly
      prolonged in the lead-exposed group, and this correlated with both blood lead
      level and age. Nevertheless, both the N75 and P100 latencies correlated with the
      concentration of delta-aminolevulinic acid (delta-ALA) in urine and age. This, at
      least in part, could be due to elevated delta-ALA levels competing at gamma
      aminobutyric acid (GABA) receptor neurons. This is consistent with the fact that
      GABA receptor neurons are involved along the entire length of the visual pathway.
      The results indicate that lead affects neural function even at permitted levels
      of exposure, and that this level should be reduced.

PMID- 8747850
TI  - Diagnosis of fatal infantile defects of the mitochondrial respiratory chain: age
      dependence and postmortem analysis of enzyme activities.
AB  - We studied two diagnostic aspects of fatal infantile defects of the mitochondrial
      respiratory chain: the age dependence of muscle mitochondrial enzyme activities
      and the reliability of diagnosis from autopsy samples. In morphologically normal
      quadriceps muscle samples of 46 children between the ages of 3 days and 15 years,
      activities of complex I plus III (NADH:cytochrome c oxidoreductase) and complex
      II plus III (succinate:cytochrome c oxidoreductase) increased 2-fold during the
      first three years of life, while that of complex II (succinate dehydrogenase),
      complex IV (cytochrome c oxidase), and citrate synthase did not show significant
      correlation with age. We suggest that these changes are related to age and stress
      the importance of strictly age-matched controls when diagnosing a mitochondrial
      disease of early childhood. The value of autopsy samples in diagnostic studies
      was evaluated by comparing mitochondrial enzyme activities in quadriceps muscle
      from autopsies and from surgical biopsies. In quadriceps muscle mitochondria, all
      the enzyme activities studied remained stable for at least 3 h after death. Using
      age-matched controls and autopsy samples, we diagnosed a respiratory chain enzyme
      deficiency in two infants, and the defects were confirmed in cultured skin
      fibroblasts.

PMID- 8747851
TI  - Improvement of lesions shown on MRI and CT scan by administration of
      dichloroacetate in patients with Leigh syndrome.
AB  - Brain lesions exhibited on MRI and CT scan in 2 patients with mitochondrial
      encephalomyelopathy representing Leigh syndrome were improved by administration
      of dichloroacetate (DCA). One patient had pyruvic acid dehydrogenase complex
      (PDHC) deficiency, the other had complex I deficiency. The efficacy of DCA was
      transient in the patient with the PDHC deficiency, lasting for about 2.5 months.
      The patient died at the age of 6, about 2 years after the initiation of DCA
      treatment. DCA administration was started in the patient with complex I
      deficiency when he was 15 months old and it is still effective at his present age
      of 24 months. His motor ability is developing, and he could walk without support
      at the age of 19 months. DCA administration should be tried in patients with
      mitochondrial diseases.

PMID- 8747852
TI  - Neurodegenerative course in ceramidase deficiency (Farber disease) correlates
      with the residual lysosomal ceramide turnover in cultured living patient cells.
AB  - Farber's lipogranulomatosis is an inborn lipid storage disease characterized by
      tissue accumulation of ceramide due to deficient activity of lysosomal
      ceramidase. Symptoms include painful swelling of joints, subcutaneous nodules, a
      hoarse cry, hepatosplenomegaly and nervous system dysfunction of markedly
      variable degree. In most cases the neural dysfunction rather than the general
      dystrophy, seems to limit the duration of Farber disease. We examined whether the
      severity can be shown as a function of ceramide turnover by lysosomal ceramidase.
      The lysosomal degradation of sphingomyelin-derived ceramide was studied in situ
      in patient skin fibroblasts and lymphoid cells loaded with LDL-associated
      radioactive sphingomyelin. We could show for the first time a significant
      correlation between the ceramide accumulated in situ and the severity of Farber
      disease. Our method provides an alternative means for determining ceramide
      degradation by lysosomal ceramidase, but in intact cells. The relatively simple
      method is at least of the same diagnostic use for Farber disease as the in vitro
      assay of acid ceramidase using cell homogenates and may also have some prognostic
      use.

PMID- 8747853
TI  - Type II muscle fibers are stained by anti-Fas antibody.
AB  - To examine whether apoptosis related proteins are present in skeletal muscles we
      studied biopsied muscles immunohistochemically and by Western blot analysis.
      Biopsied muscles from patients with several disorders were studied with anti-Fas
      antibody and anti-BCL2 antibody. Type II muscle fibers identified by ATPase
      staining were positively stained by anti-Fas antibody in both normal control and
      diseased muscles. Anti-BCL2 antibody did not stain any muscle fibers. Western
      blot analysis using anti-Fas antibody showed a single band at 45 kDa in both
      skeletal muscle and lymphocytes. Anti-Fas antibody has been reported to induce
      apoptosis in the cells. The presence of anti-Fas antibody reactive materials in
      type II muscle fibers might be related to type II fiber atrophy in muscular
      disorders.

PMID- 8747854
TI  - Autosomal dominant cerebellar ataxia deafness and narcolepsy.
AB  - A new autosomal dominant syndrome in a Swedish pedigree is described. Five
      patients were affected with cerebellar ataxia and sensorineural deafness. Four of
      these patients had symptoms of narcolepsy. Optic atrophy, other neurological
      abnormalities and psychiatric symptoms developed with increasing disease
      duration. Three patients had non-neurological disease in addition, including
      diabetes mellitus in two and hypertrophic cardiomyopathy in one. Autopsy with
      neuropathological examination was performed in one case. Molecular studies
      focused on the short arm of chromosome 6, including the HLA DR2 locus associated
      with narcolepsy and the (CAG)n repeat at the spinocerebellar ataxia type 1 (SCA1)
      locus. Biochemical investigation of muscle biopsy of one case indicated
      mitochondrial dysfunction with selective decrease in ATP production for
      substrates that normally give the highest rates. The activity of glutamate
      dehydrogenase was reduced, indicating a low mitochondrial density. We postulate
      an autosomal dominant genetic factor responsible for this syndrome. Linkage was
      excluded to HLA DR2, and a normal sized SCA1 repeat was observed. We conclude
      that a locus predisposing to ataxia, deafness and narcolepsy exists outside this
      region of chromosome 6.

PMID- 8747855
TI  - Ipsilateral thalamic diaschisis after middle cerebral artery infarction.
AB  - The significance of ipsilateral thalamic diaschisis (ITD) among patients with
      chronic, stable middle cerebral artery (MCA) infarcts was investigated. Twenty
      eight subjects with chronic MCA infarction and twenty two normal controls were
      studied with positron emission tomography (PET), using the steady state technique
      with 15O. Stroke patients were subdivided into a group with ITD (n = 12) and a
      group without ITD (n = 16). Patients with ITD had greater decreases of regional
      blood flow (rCBF) and oxygen consumption (rCMRO2) in the infarcted MCA territory,
      compared to MCA infarction without ITD. The neurological deficits at the time of
      PET scanning were similar between both groups. Extent of infarction by CT brain
      scan appeared more predominant in peri-insular regions of patients with ITD,
      while in non diaschisis patients infarcts were more widely distributed throughout
      the MCA territories. Occurrence of ITD and of crossed cerebellar diaschisis (CCD)
      did not correlate. Occurrence of ITD seems to be linked to diffuse reductions of
      blood flow and oxygen metabolism in cortical territories of the MCA. Mechanisms
      of ITD were different from those of CCD.

PMID- 8747856
TI  - Influence of age, temperature, sex, height and diazepam on vibration perception.
AB  - Vibration perception was quantitatively examined in 92 healthy volunteers (46
      females, 36 males, aged 10-71 years). Vibration perception thresholds, vibration
      disappearance thresholds and vibration thresholds were assessed at the second
      metacarpal bone, styloid process of ulna, lateral epicondyle of humerus, first
      phalanx of the big toe, first metatarsal bone, medial malleolus and proximal part
      of the tibia bilaterally. Vibration sensitivity was found to be age-dependent.
      Under the age of 60, the correlation was linear. Vibration thresholds depended on
      body site but they were not related to sex or body side. Temperature and diazepam
      affect the perception of vibration considerably. Small interindividual
      variability was found in measurements repeated in 3 consecutive days, after 4
      weeks and after a year.

PMID- 8747857
TI  - Delayed development of symptomatic improvement by (--)-deprenyl in Parkinson's
      disease.
AB  - Twenty de novo patients with Parkinson's disease (Hoehn-Yahr stages I, II, III)
      were studied in a double blind trial after introducing (--)-deprenyl monotherapy.
      The parkinsonian symptoms were assessed by a novel graded clinical rating scale,
      by UPDRS and by the North Western self-rating scale. A significant change was
      observed in motor behaviour and daily activity (UPDRS) after 3 weeks of treatment
      with (--)-deprenyl at 10 mg/day. The total scores using UPDRS and the North
      Western ratings were changed significantly after 4 weeks. The greatest changes
      observed were in walking and in hypokinesia. Rigidity was not modified by (--)
      deprenyl.

PMID- 8747858
TI  - Apolipoprotein E genotype in Spanish patients of Alzheimer's or Parkinson's
      disease.
AB  - Blood donors of the Madrid area show a 6% frequency of apolipoprotein E genotype
      carrying allele epsilon 4. This frequency is smaller than other populations of
      Caucasian origin. This proportion decreases to 4% in a selected sample of healthy
      individuals of ages > 60 years. The frequency (34%) of the allele epsilon 4 was
      significantly increased in patients of late onset Alzheimer's disease, similarly
      to other populations. An earlier age of onset of the dementia is observed in the
      patients of late-onset Alzheimer's disease carrying the allele epsilon 4. No
      increased frequency in allele epsilon 4 frequency was found in patients of early
      onset Alzheimer's disease. Patients of Parkinson's disease do not show any
      differences in the frequency of the alleles of apolipoprotein E when compared
      with healthy individuals.

PMID- 8747859
TI  - Congenital hypomyelination neuropathy: decreased expression of the P2 protein in
      peripheral nerve with normal DNA sequence of the coding region.
AB  - Congenital hypomyelination neuropathy (Lyon type) is characterized by a non
      progressive clinical course and a histopathological formation of atypical onion
      bulb. We have studied the immunohistochemical expression of the major peripheral
      myelin proteins including P0 protein, myelin basic protein (MBP) and P2 protein
      in three such patients. No significant difference was observed between the
      patients and the controls, as to the P0 and MBP staining. In contrast, P2 protein
      antiserum scarcely stained the patients' nerve fibers except for a few scattered
      adequately myelinated fibers. Assuming the pathogenetic contribution of the
      extremely decreased P2 protein to the disease, we investigated P2 protein gene by
      sequencing all coding regions but failed to detect any change in the nucleotide
      sequence. Further investigation including the analysis of promoter region of P2
      protein gene is needed to elucidate the mechanism of congenital hypomyelination
      neuropathy.

PMID- 8747860
TI  - A new familial disorder presenting with amyotrophic lateral sclerosis-like
      manifestation: a clinicopathological study.
AB  - We studied a family in which three siblings had an identical clinical feature
      indistinguishable from familial amyotrophic lateral sclerosis (ALS), consisting
      of progressive generalized neurogenic muscular atrophy with hyporeflexia and
      normal sensations beginning in the fourth decade. The duration of illness was
      about 4 years in all affected members. Autopsy of one patient revealed multiple
      foci of spongy degeneration in the white matter of the spinal cord, brain stem,
      cerebellum, and the thalamus, characterized by vacuoles of various size, foamy
      macrophages and degenerating swollen axons. These changes were most marked in the
      spinal cord, where there was neither pyramidal tract involvement nor neuronal
      loss in the anterior horn. The pathological findings were different from those of
      ALS. A similar disease affected the siblings' mother, suggesting an autosomal
      dominant inheritance. The disease in the kindred, therefore, appears to be a
      unique hereditary disorder.

PMID- 8747861
TI  - Angiographic patterns of carotid ischemic cerebrovascular disease in Saudi
      Arabia.
AB  - The angiographic findings in 100 Saudi patients with carotid ischemic
      cerebrovascular disease (CVD) (transient ischemic attacks (TIA) or strokes) were
      retrospectively reviewed. These patients were representative of all patients with
      similar disorders in the terms of sex, frequency of diabetes mellitus and
      ischemic heart disease. They were, however, significantly younger, smoked more,
      had more cervical bruits and less atrial fibrillation. Analysis of the data
      showed that a significant stenosis (> 70%) of the carotid artery origin was found
      only in 12% of TIA cases, 4% in the lacunar infarction cases and 6% of the large
      infarction cases on the symptomatic side and only in one case of TIA in the
      asymptomatic side. These frequencies were significantly lower than those found in
      similar studies performed in western countries. This study suggests that stenoses
      and occlusions of extracranial carotid artery plays a smaller role in the
      pathogenesis of ischemic CVD in Saudis than in Caucasians. The low consumption of
      cigarettes among elderly and females may be one of the explanations.

PMID- 8747862
TI  - The effect of lead exposure on target detection and memory scanning differs.
AB  - Visual event-related potentials were measured in lead-exposed and control
      subjects, while they were performing a target detection as well as a memory
      scanning task. Blood lead and urinary delta-aminolevulinic acid (delta-ALA) were
      determined in samples taken on the same day. Lead exposure did not affect the
      memory scanning P300 latency, but it did delay the target detection P300 latency
      in a dose-dependent fashion. The P300 amplitude of lead-exposed subjects was
      significantly reduced for both tasks, but not in a dose-dependent fashion. The
      target detection, but not the memory scanning, P300 latency correlated with
      urinary delta-ALA. No correlation of P300 with age was found, even though the
      subjects ranged from 20 to 60 years of age. The difference in the effect of lead
      exposure on the target detection and memory scanning P300 adds to the evidence
      that the P300 for the two tasks arises from different generators. The absence of
      a correlation of the measured P300 latency for each task with age in the present
      study raises the possibility that this extensively reported observation might, in
      part, be due to inappropriately matched younger and older subjects. This study
      indicates that evaluation of subjects exposed to toxic substances can increase
      our basic understanding of evoked potentials, as well as providing evidence of
      their toxic manifestations.

PMID- 8747863
TI  - Immunological abnormality in patients with lysinuric protein intolerance.
AB  - Lysinuric protein intolerance (LPI) is a rare hereditary disorder manifesting
      hyperammonemia induced by low levels of basic amino acids, these low levels being
      due to the impaired transport of these acids in the intestinal mucosa and the
      renal tubules. Low serum arginine levels and probably the consequently low in
      vivo levels of nitric oxide (NO), which against acts as a physiological and
      immunological mediator/modulator, are thought to influence the immunological
      status in patients with LPI. Accordingly, this study was conducted to. We found
      that patients with LPI had leukocytopenia, high serum IgG levels, a high ratio of
      CD44B4-positive lymphocytes (helper inducer) to CD42H4-positive lymphocytes
      (suppressor inducer), low levels of leukocyte phagocytic, cytotoxic, and natural
      killer cell activity, and increased spontaneous proliferation of lymphocytes.
      These results were probably the consequence of persistent low NO levels in vivo.

PMID- 8747864
TI  - On the role of human herpesvirus 6 in viral latency in nervous tissue and in
      cerebral lymphoma.
AB  - Latent infections by human herpesvirus 6 (HHV6) in nervous tissue and its role in
      human disease are poorly understood. For the present study, an improved PCR
      method has been applied to brain tissue samples from 5 different brain regions
      from 20 forensic post-mortem cases without neurologic involvement. Spleen tissue
      from these cases as well as 5 cerebral lymphoma tissue samples were also
      examined. HHV6 DNA was detected in 3 of 20 brains. The viral sequences could be
      amplified from cortical brain tissue from these 3 cases. In one of these cases,
      HHV6 DNA was detectable in two separate tissue samples. PCR was negative in brain
      lymphoma and spleen tissue. These findings point toward HHV6 latency in brain
      tissue and might thus support the reported glial tropism of this virus. No role
      could be found for HHV6 in the pathogenesis of cerebral lymphoma.

PMID- 8747865
TI  - Corpus callosum atrophy in amyotrophic lateral sclerosis.
AB  - Recent studies have suggested widespread involvement of the cerebral regions
      other than the primary motor cortex in amyotrophic lateral sclerosis. To
      investigate atrophy of the corpus callosum as a measure of cerebral pathology, we
      studied 25 right-handed patients with sporadic amyotrophic lateral sclerosis
      using magnetic resonance imaging. Five patients had cognitive decline or
      emotional and personality changes. The ratios of mid-sagittal corpus callosum
      areas to the midline internal skull surface area on T1-weighted images were
      analysed. Compared with 25 age- and sex-matched right-handed control subjects,
      the patients had significantly decreased callosal/skull area ratio, with anterior
      predominance of the degree of atrophy. The patients with cognitive decline or
      psychiatric symptoms had substantial atrophy of the anterior fourth of the corpus
      callosum. These findings suggest that atrophy of the corpus callosum, especially
      in the anterior half, is present in amyotrophic lateral sclerosis, and that
      severe atrophy in the anterior fourth is associated with cognitive decline and
      psychiatric symptoms. Callosal atrophy may reflect the widespread distribution of
      pathological changes in the cerebral cortex, which are accentuated in the frontal
      cortex.

PMID- 8747866
TI  - Masseter inhibitory reflex threshold: a novel technique for electrophysiological
      investigation of trigeminal nerve lesions.
AB  - The masseter inhibitory reflex was investigated in 60 healthy volunteers, in 38
      patients with trigeminal nerve branch lesions in the majority due to dental
      surgery, and in 9 patients with facial sensory loss and weakness caused by brain
      hemisphere lesions. The reflex threshold (TR) was almost symmetric both in normal
      subjects and in the patients with hemisphere lesions. In peripheral trigeminal
      hypaesthesia, elevation of TR on the lesioned side proved the most sensitive
      electrophysiological parameter. There was, moreover, some correspondence between
      the degree of sensory loss in hypaesthesic skin areas and elevation of TR, and
      recovery from the lesion was associated with TR normalization. Supratentorial
      lesions, in contrast, may influence the reflex pattern rather than reflex
      excitability.

PMID- 8747867
TI  - Fulminant Guillain-Barre syndrome with quadriplegia and total paresis of motor
      cranial nerves as a result of segmental demyelination.
AB  - Guillain-Barre syndrome (GBS) is a subacute demyelinating polyneuropathy with a
      monophasic course. Rarely, demyelination may be so severe as to produce
      electrically unexcitable nerves. We present a patient with fulminant onset of
      symptoms who was quadriplegic and had bilateral involvement of all motor cranial
      nerves. Serial EMGs indicated that segmental demyelination was responsible for
      these clinical findings.

PMID- 8747868
TI  - Fibrosarcomatous metastasis the central nervous system with overt hemorrhage:
      case report and review of the literature.
AB  - Sarcomatous metastasis to the central nervous is generally considered uncommon
      and rarely shows evidence of hemorrhage. Consequently, patients with fibrosarcoma
      are rarely screened for metastatic disease in the central nervous system. We
      present a case of fibrosarcoma with metastasis to brain accompanied by overt
      hemorrhage into the tumor. It is suggested that patients with fibrosarcoma be
      routinely screened for metastasis to the central nervous system and that
      sarcomatous metastasis be considered in the differential diagnosis of hemorrhagic
      CNS tumors.

PMID- 8747869
TI  - Cytomegalovirus-associated transverse myelitis in a non-immunocompromised
      patient.
AB  - Cytomegalovirus-associated transverse myelitis (TM) is rare in immunocompetent
      patients. We report here the case of a 24-year-old woman who developed acute
      transverse myelitis with cerebrospinal fluid (CSF) findings, suggesting a central
      nervous system (CNS) infection, and a positive CMV serology.

PMID- 8747870
TI  - Quantitative assessment of thermal and pain sensitivity.

PMID- 8747871
TI  - Quantitative assessment of thermal and pain sensitivity reply to the letter by S.
      Lautenbacher (J. Neurol. Sci., 134 (1995) 211)

PMID- 8747872
TI  - Spastic paraparesis and mutations in the prion protein gene.

PMID- 8747873
TI  - Changes in proximal and distal coronary artery diameter during atrial pacing
      induced myocardial ischemia.
AB  - BACKGROUND: The present study was designed to evaluate the role of tachycardia
      induced dynamic coronary artery diameter changes in the development of myocardial
      ischemia. METHODS: Coronary angiography at rest and during atrial pacing-induced
      myocardial ischemia was performed in 22 patients. The diameter of the proximal
      and the corresponding distal coronary artery segments at rest and during pacing
      was measured using quantitative coronary angiography. Plasma levels of
      noradrenaline, adrenaline, dopamine and endothelin were determined in a subset of
      14 patients in blood drawn from aorta and coronary sinus at rest and during
      pacing. RESULTS: Luminal diameter in normal proximal and distal segments
      increased, respectively, from 2.93 +/- 0.34 and 1.40 +/- 0.04 mm at rest to 3.03
      +/- 0.25 and 1.58 +/- 0.07 mm during atrial pacing. The diameter of the proximal
      coronary artery segments with significant concentric stenosis decreased from 1.28
      +/- 0.4 mm at rest to 0.95 +/- 0.34 mm during pacing, whereas segments with
      either significant eccentric or non-significant stenosis did not change
      significantly. A correlation was found between the noradrenaline level in the
      coronary sinus and the distal coronary artery diameter. CONCLUSIONS: A decrease
      in diameter of coronary artery segments with concentric stenosis during
      tachycardia might contribute to the development of myocardial ischemia. Some of
      the dynamic coronary artery changes may be influenced by the plasma level of
      noradrenaline. No evidence was found to suggest that dynamic changes in the
      diameter of proximal segments are related to the changes in diameter of the
      corresponding distal segments.

PMID- 8747874
TI  - Role of leukocytes in neointimal formation after balloon angioplasty in the
      rabbit atherosclerotic model.
AB  - BACKGROUND: Adherence and transendothelial migration of circulating leukocytes is
      one of the initial events after vascular injury. This process is mediated
      principally by the expression of integrins (CD11/C18) on the cell surface, which
      interact with their counterparts in the vessel wall cells. In order to determine
      the role of leukocytes in the development of neointimal thickening after balloon
      angioplasty, a monoclonal antibody (R15.7) against leukocyte adherence
      glycoprotein CD18 was used. METHODS: Femoral artery atherosclerotic lesions were
      induced in 20 New Zealand White rabbits, which were subjected to balloon
      angioplasty 28 days thereafter. Twelve hours before and 48 h after balloon
      angioplasty, 2 mg/kg body weight anti-CD18 or vehicle was randomly injected
      intravenously. Twenty-one days later the rabbits were killed and morphometric
      analysis performed. Measurement of functional activity of R15.7 in rabbit sera
      was performed, analyzing the capacity of the serum sample to inhibit aggregation
      of JY cells. RESULTS: The serum obtained from monoclonal antibody-treated rabbits
      showed more than 50% inhibition of cell aggregation at the time of balloon
      angioplasty. No effect on cell aggregation was seen in the sera of control
      rabbits. By angiography, there was no difference in lumen diameter and percentage
      stenosis at follow-up between the two groups. On morphometric analysis, there
      were no differences in the cross-sectional areas of intima, media, and lumen
      between the two treatment groups. The percentage cross-sectional area of intima
      was also similar in the two groups (0.672 +/- 0.04 versus 0.628 +/- 0.04).
      CONCLUSIONS: Blocking the CD18/CD11 glycoprotein pathway for leukocyte adhesion
      with a specific monoclonal antibody did not decrease the restenotic process after
      balloon angioplasty in the atherosclerotic rabbit arterial injury model.

PMID- 8747875
TI  - Dynamics of left ventricular thrombi in patients with acute anterior myocardial
      infarction treated with thrombolytics.
AB  - BACKGROUND: Limited data exist concerning left ventricular thrombi during and
      after hospitalization in patients treated according to modern principles. The
      purpose of the present study was to examine the formation and resolution of left
      ventricular thrombi during the first month in patients with acute anterior
      myocardial infarction treated with streptokinase and aspirin. METHODS: Seventy
      seven consecutive patients were studied prospectively during the hospital stay
      and 1-month follow-up study. Aspirin was used routinely, whereas anticoagulants
      were only used after a decision by the attending physician. Echocardiography was
      performed within 3 days of admission, before hospital discharge and after 1 month
      of follow-up. RESULTS: At the first examination, 17 of 77 patients (22%) had a
      thrombus. At discharge, 73 patients remained in the study. In five (31%) of the
      16 patients with early thrombus, the thrombus persisted; in 18 (32%) of the 57
      patients without early thrombus, a new thrombus was diagnosed. One month later,
      65 patients remained eligible for follow-up study. In three of 20 patients (15%)
      the thrombus from the second examination persisted and in four of 45 patients
      (9%) a new thrombus was diagnosed. The disappearance rate between the second and
      third examination was high irrespective of whether patients were treated with
      anticoagulants (eight of nine, 89%) or not (nine of 11, 82%). Extensive left
      ventricular segmental dysfunction and signs of congestive heart failure were
      associated with the appearance of a left ventricular thrombus. No embolic events
      were recorded. CONCLUSION: In patients with anterior myocardial infarction
      treated with streptokinase and aspirin the development and disappearance of left
      ventricular thrombi is a highly dynamic process. A large proportion of thrombi
      resolve without additional anticoagulant therapy.

PMID- 8747876
TI  - Does magnesium modify left ventricular remodeling after experimental myocardial
      infarction?
AB  - BACKGROUND: Magnesium therapy has been shown to improve survival and decrease the
      incidence of left ventricular failure when given to patients shortly after a
      myocardial infarction, but the mechanisms are unknown. We tested the hypothesis
      that the benefits of magnesium therapy are due to a favorable effect on early
      left ventricular remodeling, particularly on infarct shape changes. METHODS: Rats
      were infarcted and randomly allocated to two groups: group 1 (n = 8) received
      intravenous magnesium sulfate (200 mumol/kg) over 10 min started 30 min after
      coronary ligation, then an intraperitoneal dose (800 mumol/kg), which was
      repeated 6 h later. Group 2 (n = 10) served as a control group, and received
      normal saline. Using this regimen, the trough level of ionized magnesium 12 h
      after the intravenous dose was 33% above the control level. Three weeks after
      infarction, the hearts of the rats were arrested with saturated potassium
      chloride and fixed in formalin at 7.5 mmHg. The hearts were cut transversely into
      four slices. Photographs of both sides of each slice were taken and projected for
      morphometric analysis. RESULTS: Infarct size was similar in the magnesium and
      control groups (35 +/- 4 versus 30 +/- 2%). Infarct thickness, expansion index,
      and cavity area were also similar in both groups. CONCLUSIONS: Magnesium has no
      effect on early left ventricular remodeling or infarct expansion. The mechanism
      of its clinical benefits remains unexplained.

PMID- 8747877
TI  - Scintigraphic visualization of pulmonary thrombi with 123I-YPACK-TNK-tPA.
AB  - BACKGROUND: We have previously demonstrated that radiolabeled tissue-type
      plasminogen activation (tPA) in which the plasminogen-activating catalytic site
      has been inactivated binds avidly to thrombi and can be used for scintigraphic
      detection of pulmonary thrombi in vivo. The present study was performed to
      overcome identified limitations of the initially developed approach and to
      determine whether a tracer made with a molecular variant of tPA, TNK-tPA, would
      provide superior images of pulmonary thrombi and hence facilitate differential
      diagnosis of pulmonary embolism from acute myocardial infarction. It was thought
      that TNK-tPA may be superior in view of its longer biological half-life and less
      avid uptake by macrophages that would otherwise contribute to high background
      because of non-clot-selective uptake of the tracer. METHODS: 123I
      tyrosylprolylarginyl chloromethyl ketone (123I-YPACK-TNK-tPA) was infused into
      the systemic circulation of dogs with either pulmonary or right ventricular
      thrombi induced with thrombogenic tips of modified guide wires. Planar and single
      photon emission computed tomography (SPECT) scintigraphic data were obtained, and
      blood and tissue samples were acquired for analysis of the distribution of the
      radiotracer over time. RESULTS: Tracer cleared from blood with an alpha phase
      half-life of 10 +/- 1 min, paralleling the clearance of unlabeled TNK-tPA. Only
      minimal release of labeled fragments from liver into blood occurred during the
      entire time course of the imaging studies. Pulmonary thrombi were visualized with
      SPECT within 30-120 min in all dogs. Images were superior to those obtained after
      infusion of labeled wild-type tPA, primarily because of diminished background
      radioactivity and consequently increased scintigraphic contrast. In one dog which
      had a right ventricular thrombus, the thrombus was readily detectable in both
      planar and SPECT images. CONCLUSIONS: Radiolabeled TNK-tPA in which plasminogen
      activating activity has been inhibited biochemically is an excellent
      radiopharmaceutical for prompt scintigraphic detection of pulmonary and
      ventricular thrombi in vivo, and an attractive candidate for rapid, sensitive and
      non-invasive diagnosis of pulmonary thromboembolic disease in patients.

PMID- 8747878
TI  - Regional diastolic wall motion dynamics in anterior myocardial infarction:
      analysis and quantification with magnetic resonance imaging.
AB  - BACKGROUND: Regional variability in systolic and diastolic cardiac function
      occurs in most cardiac disorders. The influence of this regional functional
      heterogeneity on global function is not well understood and is difficult to study
      with the common imaging modalities. METHODS: A midventricular short axis slice of
      the left ventricle was obtained with ECG-triggered magnetic resonance imaging in
      eight infarct patients and 10 control volunteers. The variation in wall thickness
      and slice cavity volume during the cycle was studied using the centreline method.
      RESULTS: The peak filling rate was significantly decreased in the infarct group
      (96 versus 58 cm3/s, P < 0.005). In addition, a small contribution of other
      parameters, such as the time to end systole, the isovolumic relaxation time, and
      the duration and extent of early filling, was also shown by linear discriminant
      analysis. Analysis of the regional parameters demonstrated an increased
      asynchronicity of contraction (64 versus 37 ms, P < 0.01) as well as relaxation
      (88 versus 51 ms, P < 0.01) in patients with myocardial infarction. On comparison
      of the anterior (infarcted) and inferior (non-infarcted) parts of the left
      ventricle, the difference was present only in the infarct region. CONCLUSION:
      Magnetic resonance imaging of the heart allows evaluation of the relationship
      between regional differences in wall motion dynamics and global parameters of
      diastolic function in infarct patients.

PMID- 8747879
TI  - Extensive endarterectomy of the left anterior descending coronary artery combined
      with coronary artery bypass grafting.
AB  - BACKGROUND: Complete revascularization of a diffusely diseased left anterior
      descending (LAD) coronary artery can be accomplished by extensive endarterectomy
      in conjunction with coronary artery bypass grafting (CABG). The present study was
      designed to assess the safety of the procedure, and which techniques lead to the
      best short- and long-term results. METHODS: Between January 1990 and October 1994
      106 patients underwent extensive open endarterectomy of the LAD coronary artery
      combined with CABG at our institution. This group constituted 4.9% of all
      patients undergoing CABG during this period. The mean age of those studied was
      64.4 +/- 9.2 years and 92% were male. In 22 patients (21%) the procedure was a
      repeat CABG and 12% had had percutaneous transluminal coronary angioplasty prior
      to the operation. Ninety-one per cent of the patients were in Canadian
      Cardiovascular Society (CCS) angina class 3 or 4, 91% had three-vessel disease
      and 36% had unstable angina at the time of surgery. The mean preoperative left
      ventricular ejection fraction was 53.6 +/- 14.9% (range, 15-80%). The internal
      mammary artery (IMA) was used to bypass the LAD coronary artery in 40 patients
      (38%) and a saphenous vein graft (SVG) was used in 66 patients. In 25 of the IMA
      bypass group an additional venous patch was used (IMA+P). RESULTS: The overall
      mortality rate was 9.4% (10 patients), including seven immediate postoperative
      deaths. When the IMA was used as a conduit the mortality rate was only 5.0%.
      There were seven (6.6%) postoperative non-fatal myocardial infarctions. There was
      a low incidence of other postoperative complications, similar to that following
      CABG without endarterectomy performed during the same period. Multivariate
      analysis identified emergency operation, two-vessel endarterectomy and female sex
      as independent risk factors for mortality. Upon follow-up study of 94 hospital
      survivors (98%), at a mean of 26.5 months (range, 1-48 months), all
      endarterectomy patients were in CCS class 1 or 2. Seventy-eight patients (83%)
      had an excellent postoperative exercise tolerance and the left ventricular
      function was preserved. The 4-year survival rates were 88% and 96% and the
      cardiac event-free survival rates were 74% and 87% in the SVG and IMA groups
      respectively. CONCLUSIONS: Complete revascularization of the diffusely diseased
      LAD coronary artery can be accomplished by adjunctive open endarterectomy with a
      degree of operative risk (mortality 9% and incidence of non-fatal myocardial
      infarction 7%). The immediate and medium-term results are improved when the IMA
      is used as a conduit, with or without additional venous patch. Independent risk
      factors for mortality were two-vessel endarterectomy, female sex and emergency
      operation. The long-term results revealed an overall survival rate of 92% and a
      cardiac event-free survival rate of 79% at 4 years, as well as excellent
      functional results.

PMID- 8747881
TI  - Bibliography of the current world literature.

PMID- 8747880
TI  - The open infarct-related artery: theoretical and practical considerations.

PMID- 8747882
TI  - Antibodies directed to restricted sequences of the c-Erb A alpha hinge domain
      interfere with hormone or DNA binding to recombinant alpha-type triiodothyronine
      receptor (c-Erb A alpha1) and detect structural changes.

PMID- 8747883
TI  - Iodination of mouse EGF with chloramine T at 4 degrees C: characterization of the
      iodinated peptide and comparison with other labelling methods.
AB  - A modified Chloramine T labelling procedure was used to iodinate mEGF in order to
      perform radio-receptor assays. The reaction was conducted at 4 degrees C with 1
      mu g Chloramine T only. The tracer obtained was characterized by its maximal
      binding, specific activity and binding properties compared with the native
      peptide. Fast Liquid Protein Chromatography was performed to analyse the
      homogeneity of the preparation and membrane extracts from A431 cells were used to
      purify the tracer. The modified Chloramine T procedure was compared with two
      other methods: the classical Chloramine T iodination and the labelling procedure
      using Enzymobeads. The modified Chloramine T procedure is reproducible, provides
      labelled mEGF with high binding capacity (65 to 80% with canine placental
      membrane extracts) and high specific activity (351 +/- 107 mu Ci/mu g mEGF) and
      seems to preserve the binding properties of the native peptide.

PMID- 8747884
TI  - Identification of a membrane-associated receptor for transforming growth factor
      type E.
AB  - We have identified the receptor for epithelial type transforming growth factor
      (TGFe). TGFe, a member of the epithelin/granulin family of proteins, is present
      primarily in tissues of epithelial origin. It is a powerful mitogen for
      epithelial and fibroblastic cells. TGFe, iodinated using an immobilized glucose
      oxidase-lactoperoxidase method, was chemically crosslinked to receptors on
      membranes isolated from SW-13 adrenal carcinoma cells by the crosslinker
      disuccinimidyl suberate (DSS). The receptor appears to be a protein which
      migrates at an apparent molecular weight of approximately 170-175 kDa under
      reducing and nonreducing conditions in SDS-polyacrylamide gels.

PMID- 8747885
TI  - Mg2+ enhances high affinity [3H]8-hydroxy-2-(di-n-propylamino) tetralin binding
      and guanine nucleotide modulation of serotonin-1a receptors.
AB  - The effects of MgCl2 on the binding of the serotonin 1a (5HT1a) receptor agonist
      8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) to bovine hippocampal
      membranes were investigated. MgCl2 was found to enhance both [3H]8-OH-DPAT
      binding and guanine nucleotide modulation of high affinity binding. The effect of
      Mg2+ on promoting high affinity agonist binding was due to a 3.3 fold decrease in
      the dissociation constant rather than an increase in the number of binding sites.
      Mg2+ acted to increase the efficacy of the nonhydrolyzable GTP analog 5'
      guanylylimidodiphosphate (GppNHp) in promoting the interconversion of high and
      low affinity states. Addition of MgCl2 significantly increased the sensitivity of
      [3H]8-OH-DPAT binding to GppNHp, decreasing the concentration needed for half
      maximal inhibition of binding from greater than 50 mu M to 300 nM. Our findings
      that Mg2+ enhances high affinity [3H]8-OH-DPAT binding without change in number
      of binding sites and that guanine nucleotide modulation of binding can occur in
      the absence of Mg2+ suggests that ternary complex formation between receptor,
      ligand and G-protein can occur in the absence of Mg2+.

PMID- 8747886
TI  - Effect of cycloheximide on eclosion hormone sensitivity and the developmental
      appearance of the eclosion hormone and cGMP regulated phosphoproteins in the CNS
      of the tobacco hornworm, Manduca sexta.
AB  - The neuropeptide, eclosion hormone (EH), triggers ecdysis behavior at the end of
      each molt in Manduca sexta. Previous studies have shown that the action of EH is
      mediated by an increase in cGMP and is associated with the phosphorylation of two
      proteins, named the EGPs. The ability of insects to respond to EH is
      developmentally regulated with sensitivity being first seen at about 8 hr prior
      to the normal time of ecdysis. The EGPs are also first detectable in the CNS at 8
      hr prior to ecdysis, suggesting that it is their synthesis which determines EH
      sensitivity. The protein synthesis inhibitor, cycloheximide was used to study the
      development of the events leading to pupal ecdysis in Manduca. The results of
      these experiments suggest that protein synthesis is necessary about 10 hr before
      ecdysis for both the development of EH sensitivity and for the appearance of the
      EGPs.

PMID- 8747887
TI  - Commentary: mannitol: molecule magnifique or a case of radical misinterpretation?
AB  - Reactive oxygen species are constantly formed in biological systems. When
      production exceeds antioxidant protection, oxidative stress leading to molecular
      damage occurs. The most reactive ROS in biological systems is the hydroxyl
      radical which damages adjacent molecules at diffusion controlled rates. The
      possibility of preventing such chemistry inside cells with therapeutic doses of
      mannitol at present seem remote.

PMID- 8747888
TI  - Semiquinone free radical formation by daunorubicin aglycone incorporated into the
      cellular membranes of intact Chinese hamster ovary cells.
AB  - The production of semiquinone free radicals has been measured by electron
      paramagnetic resonance spectroscopy (EPR) in Chinese hamster ovary cells in which
      7-hydroxy daunorubicin aglycone had been incorporated. The highly lipophilic
      daunorubicin aglycone was incorporated into the cellular membrane by swirling a
      cell suspension over a thin layer of daunorubicin aglycone. Thus, the observed
      semiquinone free radical was likely formed directly in the lipophilic environment
      of the cellular membrane. The linewidth of the observed EPR signal suggested that
      a neutral protonated semiquinone species was formed. In the presence of the cell
      impermeant paramagnetic line broadening agent chromium(III) oxalate, no
      detectable signal was observed. This result indicates that even though the
      semiquinone is embedded in the membrane, it is still partly accessible to the
      external chromium(III) oxalate. Analysis of chloroform extracts of the cells
      after EPR experiments indicated that daunorubicin aglycone was extensively
      metabolized. The results of a growth inhibition assay carried out on cells into
      which daunorubicin aglycone had been incorporated showed almost no effect on cell
      growth. This result indicates that in spite of significant daunorubicin aglycone
      induced radical formation taking place directly in the cell membrane, little cell
      damage results.

PMID- 8747889
TI  - Redox behaviour of phenolic porphyrins in basic solutions: a reappraisal.
AB  - Phenolic porphyrins 1, 4, and 5 form stable phenoxyl radicals 3, 6, and 7 in
      deoxygenated as well as oxygenated basic solutions. Mechanistic schemes are
      presented, involving coupled disproportionation and conproportionation reactions,
      that do not require oxygen involvement in the redox processes leading to phenoxyl
      radicals.

PMID- 8747890
TI  - The effect of exogenous adenosine on functional injury caused by hydrogen
      peroxide in the isolated rat heart.
AB  - Adenosine is an endogenous cardioprotective substance. The present study examines
      whether exogenous adenosine attenuates cardiac injury induced by oxidative
      stress. Rat hearts (Langendorff model) were perfused with H2O2 (180 microM) for
      10 min, then recovered for 60 min (n = 10). In other groups adenosine 55 microM,
      11 0 microM, or 220 microM (n = 10 in each) was given in addition to H2O2
      throughout perfusion. Control perfusion with Krebs Henseleit only (n = 7),
      adenosine 110 microM throughout perfusion (n = 7), and adenosine 110 microM as an
      intervention (n = 7) was performed. The hearts were paced at 320 beats/min. Left
      ventricular systolic (LVSP) and end-diastolic (LVEDP) pressures were measured
      together with coronary flow (CF), and left ventricular developed pressure (LVDP =
      LVSP - LVEDP) was calculated. H2O2 decreased LVSP from 105 +/- 8 to 60 +/- 5 mmHg
      (mean +/- SEM) after 10 min infusion (p < 0.008). Adenosine did not attenuate the
      decrease of LVSP. LVEDP increased from 0 to 59 +/- 10 mmHg (p < 0.004) and 62 +/-
      11 mmHg 5 and 15 min after end of infusion of H2O2, respectively. Neither 55
      microM nor 220 microM adenosine inhibited the H2O2-induced increase of LVEDP.
      Adenosine 110 microM attenuated the increase after 15 (15 +/- 4 mmHg, p < 0.004)
      and 25 min observation (26 +/- 7 mmHg, p < 0.012). Adenosine did not attenuate
      the reduction of LVDP. CF initially increased during infusion of H2O2, thereafter
      decreased. Hearts given adenosine had higher basal CF, and CF did not increase
      after H2O2. Control perfusion with adenosine, given throughout perfusion or as an
      intervention, increased CF and tended to increase LVSP. In summary, adenosine did
      not inhibit H2O2-induced depression of contractility or reduction of CF. One
      concentration of adenosine (110 microM) attenuated H2O2-induced impairment of
      relaxation. Exogenous adenosine does not have an important influence on
      functional injury caused by exogenous oxidants.

PMID- 8747891
TI  - Suppression by anticancer agents of reactive oxygen generation from
      polymorphonuclear leukocytes.
AB  - The influence of anticancer agents on signal transduction for reactive oxygen
      generation was examined in polymorphonuclear leukocytes (PMN). Inositol 1,4,5
      trisphosphate and diacyl glycerol levels in formyl-methionyl-leucyl-phenylalanine
      (FMLP)-stimulated PMN were decreased by cis-diammine-dichloroplatinum (CDDP), 5
      fluorouracil (5-FU), 137Cs, and peplomycin (PLM, a bleomycin analog) in this
      order. Intracellular calcium ([Ca2+]i) level and protein kinase C (PKC) activity
      in the membrane after phorbol myristate acetate (PMA) stimulation were decreased
      by 5-FU and CDDP but not by 137Cs and, in contrast, were increased by PLM. The
      level of [Ca2+]i was decreased by 8 h treatment with 5-FU and CDDP. 5-FU and CDDP
      inhibited tyrosine phosphorylation of 83-kDa and 115-kDa proteins, however 137Cs
      did not inhibit their phosphorylation and PLM enhanced the tyrosine
      phosphorylation. Short term (< or = 4 h) treatment with PLM, 5-FU and CDDP
      enhanced respiratory burst of PMN, whereas long term (8 h) treatment, as well as
      radiation, suppressed reactive oxygen generation from PMN in a dose dependent
      manner. Genistein suppressed chemiluminescence in 5-FU-, CDDP-, and 137Cs
      pretreated PMN to a greater extent than it did in PLM-pretreated PMN, however
      near suppression of chemiluminescence by staurosporine, 4-bromophenyl bromide and
      methionine was observed in PMN pretreated with these agents. In conclusion, these
      results indicate that long term treatment of PMN with 5-FU and CDDP inhibit
      respiratory burst, suppressing intracellular calcium mobilization, PKC
      translocation and tyrosine kinase activation, in adverse, short term treatment
      with PLM enhances PKC translocation and tyrosine kinase activation, but inhibits
      myeloperoxidase (MPO) activity, and radiation causes weak inhibition of signal
      transduction for respiratory burst.

PMID- 8747892
TI  - The iron-selective chelator desferal can reduce chelated copper.
AB  - It was shown that the iron-selective chelator desferal (desferrioxamine
      mesylate:DFO) can reduce Cu(II) as judged by measuring the formation of the
      complex between Cu(I) and a specific chelator for this species, neocuproine (NC),
      in phosphate buffer. It was found that under optimal conditions, 3 moles of
      Cu(II) could be reduced per mole of DFO. Studies of the kinetics of Cu(II)
      reduction by DFO revealed that the rate of Cu(II) reduction by DFO was
      considerably slower than that by ascorbate. In the case of both reductants, even
      in the absence of NC, Cu(I) complexes remained in aqueous solutions for at least
      30 min. DFO could also reduce Cu complexed to histidine. The results presented
      highlight the interpretive dangers which can arise in studies involving multiple
      transition metals, especially in the presence of multiple chelators.
      Specifically, when desferal is used, it is important to be aware that any copper
      present may become reduced, and that any Cu(I) formed might participate in
      ongoing redox reactions.

PMID- 8747893
TI  - Potential role of the peroxidase-dependent metabolism of serotonin in lowering
      the polymorphonuclear leukocyte bactericidal function.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) significantly and dose-dependently
      suppressed the luminol-enhanced chemiluminescence (CL) signal generated by
      polymorphonuclear leukocytes (PMN) activated with phorbol myristate acetate
      (PMA), but did not modify either lucigenin-enhanced CL or the reduction of
      superoxide dismutase-inhibitable cytochrome c. Moreover, stimulation of PMNs
      previously incubated with 5-HT resulted in a threefold increase in 5-HT
      equivalents bound to the proteins of PMN. The addition of catalase or sodium
      azide substantially reduced this binding. The present results suggest that 5-HT
      metabolism is mediated by H2O2 and myeloperoxidase (MPO) released by activated
      PMNs. Hence 5-HT could lower the bactericidal function of these cells by
      competition with hypochlorite formation from halides and MPO/H2O2.

PMID- 8747894
TI  - Influence of the environment in space on the biochemical characteristics of human
      low density lipoproteins.
AB  - The purpose of this experiment was to study the efficiency of protective
      substances on the effects of cosmic radiation in space on low density
      lipoproteins. This environment induced modifications in LDL consisting of an
      increase of lipid peroxidation markers (hydroperoxides, thiobarbituric acid
      reactive substances). In contrast, apo B was not affected by cosmic radiation as
      shown by the stability of the trinitrobenzenesulfonic acid reactivity and the
      tryptophan content. Furthermore, oxidation of LDL was partially inhibited by the
      addition of cysteamine or/and probucol before the spaceflight experiment. The
      hydroperoxide formation was almost completely inhibited by cysteamine. It was
      concluded that antioxidants can exert a protective effect against peroxidative
      stress induced by the space environment.

PMID- 8747895
TI  - Air embolism during cardiopulmonary bypass.

PMID- 8747896
TI  - Paediatric perfusion practice in North America: an update.
AB  - In August 1994, an updated survey questionnaire was mailed to each paediatric
      open-heart surgery programme in North America as a follow-up to the 1989
      paediatric survey. The survey requested demographic data, equipment selection
      criteria and specific perfusion techniques for paediatric patients. The earlier
      survey revealed a wide range of clinical practice. Data from the recent survey
      were compared with the 1989 survey to identify current programme demographics and
      trends in equipment use and techniques. Responses were received from 125
      hospitals (110 active programmes and 15 programmes that do not perform paediatric
      open-heart surgery) for a response rate of 74%. Of the 110 active centres, 77
      perform both adult and paediatric cardiac surgery, and 33 perform paediatric
      surgery exclusively. Forty-three centres reported that they perform paediatric
      cardiac transplantation, an increase from 35 centres in 1989. Total caseload
      increased by more than 8% per year from 1988 to 1994. In 1994, 18% of the
      patients were operated upon during the first month of life (versus 15% in 1989),
      and 46% were operated on during the first year of life (versus 45% in 1989).
      While the 1989 survey was characterized by a high degree of heterogeneity in
      equipment and techniques, the recent survey reveals a trend toward homogeneity
      among respondents. The use of membrane oxygenation and arterial line filtration
      has become universal, and there was an increase in the use of all types of safety
      devices in the cardiopulmonary bypass circuit.

PMID- 8747897
TI  - The haemodynamic effects of the thromboxane A2 receptor antagonist GR32191B
      during cardiopulmonary bypass in the dog.
AB  - This study examined whether treatment with the specific thromboxane (TX) A2
      receptor antagonist GR32191B would result in an improvement in peripheral
      haemodynamics during and after cardiopulmonary bypass (CPB) in anaesthetized dogs
      compared with animals given either saline (control) or aspirin. Following
      thoracotomy, heparinization and aortic cannulation, and 35 minutes before CPB,
      dogs received intravenously either GR32191B (15 micrograms/kg/min), saline (50 ml
      bolus) or aspirin (225 mg bolus) (n = 6 per group). Cardiac output (dye
      dilution), femoral artery blood flow (electromagnetic flowmeter), gastrocnemius
      muscle tissue perfusion (133Xe clearance), retinal blood flow (fluorescein
      angiography), and thromboxane biosynthesis (urinary excretion rates of TXB2 and
      the metabolite 2,3-dinor-TXB2) were measured before, during and after a standard
      90 minute period of CPB at 2.4 l/min/m2 and 28 degrees C. The aspirin-treated
      group manifested an eightfold reduction in TXB2 excretion compared with controls,
      indicating a decrease in TXA2 biosynthesis. There were few haemodynamic
      differences between the groups, though the aspirin-treated group had better
      maintained muscle tissue perfusion post-CPB and significantly fewer retinal
      microcirculatory occlusions than GR32191B-treated animals. We conclude that
      specific TXA2 receptor antagonism provides no significant improvement in
      peripheral haemodynamics; rather aspirin provides a modest haemodynamic benefit.

PMID- 8747898
TI  - A comparison of albumin, polygeline and crystalloid priming solutions for
      cardiopulmonary bypass in patients having coronary artery bypass graft surgery.
AB  - This study was designed to assess the effect of different prime solution
      compositions on a patient's fluid balance, transfusion requirements, renal
      function and haemodynamic stability over the first 24 hours postbypass. Ninety
      three patients presenting for first-time coronary artery bypass graft (CABG)
      surgery were randomly allocated to receive one of three prime solutions for the
      CPB pump: albumin (4.6%) + Plasmalyte (Group A, n = 32), polygeline (Hemaccel) +
      Plasmalyte (Group P, n = 29), or crystalloid (Plasmalyte) alone (Group C, n =
      32). Patients, anaesthetists, surgeons and intensive care unit (ICU) staff were
      all blinded as to the solution type. The groups were demographically and
      haemodynamically similar. There were no differences between the groups with
      respect to white cell or platelet counts during the study. There was a
      significant difference in haemoglobin levels between the groups on weaning from
      CPB and on arrival in the ICU (Group C > Groups P and A, p < 0.001 for both
      times). There was no difference in blood transfusion requirements between any of
      the groups. During CPB, Group C required significantly more crystalloid than the
      other groups (p < 0.001). Urine output was significantly higher in Group C
      compared with Groups P and A at all time periods up to and including ICU 12 hours
      (p < 0.05). The use of frusemide was significantly higher in the ICU in Groups P
      and A (p < 0.01). There was a net gain of 3132 +/- 412 ml in Group C in 24 hour
      fluid balance, which was significantly higher than Group A (2166 +/- 223 ml, p =
      0.04). Our results show that, in this patient population, there is no advantage
      in using a colloid-based prime solution over a purely crystalloid solution from a
      haemotologic or haemodynamic point of view for the first 24 hours after CPB.
      There appears to be an increase in extracellular fluid (ECF) retention in Group
      C, but this caused no related problems in the study period. On the other hand,
      diuretics (frusemide) needed to be given significantly less often in these
      patients to offset oliguria.

PMID- 8747899
TI  - Clinical performance of a high-efficiency rapid flow leucocyte removal filter for
      leucocyte depletion of heparinized cardiopulmonary bypass perfusate.
AB  - The method of leucocyte depletion has been recently introduced to the field of
      cardiopulmonary bypass to reduce leucocyte-mediated organ dysfunction. In this
      study, we evaluated the efficacy and biocompatibility of the Pall RC400 filters
      for leucocyte depletion of heparinized cardiopulmonary bypass (CPB) perfusate
      taken from the heart-lung machine during routine cardiac surgery. For each
      filter, 700 ml blood were used as filtrate. Filtration was divided into the
      following groups to study the effect of loading pressure on the efficacy of the
      filters: under gravity pressure as a control (n = 8), under 100 mmHg (n = 8), 200
      mmHg (n = 8), and 300 mmHg loading pressure (n = 8) driven by a roller pump. In
      addition, heparinized predonation blood taken at the beginning of CPB (n = 8) was
      filtered under gravity in comparison with the perfusate taken at the end of CPB.
      The results showed that the average leucocyte removal rate by an RC400 filter for
      700 ml of blood was 96.8%. There was no significant difference of leucocyte
      removal rate between filtration under gravity and under loading pressure up to
      300 mmHg. This allows clinical filtration at a speed up to 500 ml/min. The
      platelet removal rate was significantly higher in blood taken at the beginning of
      CPB than in blood taken at the end of CPB. Complment split product, C5a,
      increased only slightly during filtration indicating that this filter, made from
      polyester, has a good blood compatible characteristic. We conclude that the Pall
      RC400 leucocyte removal filter is suitable and safe to be used for leucocyte
      filtration of heparinized CPB perfusate during cardiac surgery.

PMID- 8747900
TI  - A mathematical analysis of haemorheologic factors during cardiopulmonary bypass
      for congenital heart disease.
AB  - Rheologic properties of blood are impaired by cardiac surgery using
      cardiopulmonary bypass. This study was set out to establish a mathematical model
      in order to assess seven known haemorheologic factors and evaluate their degrees
      of influence on blood rheology in cardiopulmonary bypass. Sixteen patients
      undergoing elective congenital cardiac surgery were studied. High shear blood
      viscosity, low shear blood viscosity, haematocrit, red blood cell filtration
      rate, red blood cell electrophoresis time, plasma viscosity and fibrinogen were
      monitored. The method for mathematical calculation was the stepwise regression
      analysis. The results showed that both high shear and low shear blood viscosity
      were mainly influenced by haematocrit and plasma viscosity. Red blood cell
      filterability contributed more than red blood cell electrophoresis time for low
      shear blood viscosity. The mathematical model was re-tested statistically and
      demonstrated that the selected factors in the model represented approximately 75%
      of rheologic changes during the surgery. Therefore, this mathematical analysis
      can be used to estimate the role of various possible haemorheologic factors and
      evaluate cardiopulmonary bypass techniques and therapeutic interventions.

PMID- 8747901
TI  - Patterns of Cryptosporidium oocyst shedding in calves and a comparison of two
      diagnostic methods.
AB  - Cryptosporidium spp. oocyst shedding was observed in calves from approximately 1
      to 30 days of age. Oocysts were detected by either the Kinyoun acid-fast staining
      technique (microscopic examination--ME) or a commercially produced enzyme
      immunoassay EIA). Test concordance between the two detection methods was
      determined. The mean (+/- SD) number of days to detection of cryptosporidial
      oocysts was 9.52 +/- 1.92 for the ME and 9.83 +/- 3.19 for the EIA. No
      significant difference between the means was found (P = 0.17). The period
      prevalence of cryptosporidiosis was 100% in calves from 1 to 30 days of age. The
      overall agreement between the ME and EIA was 72%, with a kappa value of 0.42 (SE
      +/- 0.05). McNemar's test indicated that the proportion of tests determined
      positive by the two methods was not equal (P < 0.01). The findings or this study
      indicate moderate agreement between the two diagnostic methods, with the EIA
      being the more sensitive of the two. However, in most cases the herd-level
      determination of cryptosporidiosis requires minimal sample sizes and is more
      economically and easily accomplished by the ME method of detection.

PMID- 8747902
TI  - Antigenic alteration in major piroplasm surface proteins of Theileria sergenti
      during infection.
AB  - Theileria sergenti piroplasms were purified from different parasitemia peaks of
      cattle infected with parasitized erythrocytes or sporozoites during persistent
      infection. Their reactivities with monoclonal antibodies 13F5 and C9, which
      recognize 23 kDa and 32 kDa piroplasm surface proteins, respectively, were
      analyzed. Antigenic differences were observed among parasites from different
      parasitemia peaks during persistent infection when cattle were infected with
      sporozoites. Results of two-dimensional polyacrylamide gel electrophoresis showed
      that the 23 and 32 kDa proteins were expressed in all samples tested, regardless
      of their reactivities with the monoclonal antibodies. In contrast, parasites
      obtained from cattle inoculated with parasitized erythrocytes showed no antigenic
      alteration over a 2 month observation period. The results suggest that antigenic
      alteration of T. sergenti during persistent infection is related to whether the
      parasites proliferate through extraerythrocytic schizont stage in cattle or
      sporozoite and other sexual stages in tick vector.

PMID- 8747903
TI  - Vaccination of vervet monkeys against cutaneous leishmaniosis using recombinant
      Leishmania 'major surface glycoprotein' (gp63).
AB  - Vervet monkeys (Cercopithicus aethiops) were shown to give a positive delayed
      type hypersensitivity (DTH) reaction to gp63, a major surface glycoprotein of
      Leishmania parasites, and also produce antibodies to the molecule following a
      triple vaccination with a total dose of 150 micrograms of recombinant gp63 mixed
      with Bacille Calmette Guerin (BCG). However, peripheral blood leucocytes (PBL)
      from these animals neither proliferated nor produced any interferon-gamma (IFN
      gamma) following in vitro stimulation with the antigen. Analysis of lymphocyte
      subsets following vaccination did not reveal any striking phenotypic alteration
      of cellular sub-populations in PBL. When vaccinated animals were rechallenged,
      via the needle, with virulent Leishmania major promastigotes containing salivary
      gland extracts from vector sandflies, only partial protection was achieved. We
      concluded from these studies that rgp63 produced in Escherichia coli is a safe
      vaccine molecule which gives only partial protection following vaccination in the
      vervet monkey host. The molecule requires further improvement for vaccine and/or
      immunodiagnosis application.

PMID- 8747904
TI  - Differences in cloning and sub-cloning success rates in four stocks of
      Trypanosoma evansi and variation in suramin resistance of the clones.
AB  - Four Trypanosoma evansi stocks with sensitivity to suramin in mice ranging from
      0.05 to 160 mg kg-1 were cloned and sub-cloned and the sensitivity of the clones
      determined. The results suggest that it is easier to clone and sub-clone
      trypanosome stocks which are sensitive to suramin than those that are resistant
      to the action of the drug. The clones obtained from the four stocks had
      sensitivities to suramin which were similar to or different from the parent
      stocks. These results are important in view of the development of resistance for,
      in the presence of suramin, these resistant yet heterogeneous populations would
      provide the material from which selective processes could operate. These
      observations also suggest that the maintenance and spread of suramin-resistant
      trypanosomes might be curtailed by their comparative inability to establish
      themselves in a new host.

PMID- 8747905
TI  - Clearance of Theileria sergenti-infected bovine red blood cells in severe
      combined immune deficiency mice.
AB  - Clearance of Theileria sergenti-infected bovine red blood cells (Bo-RBCs) from
      the blood circulation of severe combined immune deficiency (SCID) mice was
      studied to help understand the mechanisms of anemia developing in cattle infected
      with T. sergenti. For the clearance test, Bo-RBC samples having 2%, 58%, and 76%
      parasitemia and, as a control, parasite-free Bo-RBCs were prepared in the Bo-RBC
      SCID mouse model. The T. sergenti-infected Bo-RBCs and the uninfected control Bo
      RBCs were separately labeled with two, green and red, fluorescent dyes, mixed
      together, and injected intravenously into SCID mice. The blood samples collected
      at various time points were observed under a fluorescent microscope, and the
      numbers of green and red fluorescing RBCs were counted differentially to
      determine the clearance rates of T. sergenti-infected and uninfected Bo-RBCs.
      This test clearly demonstrated that the Bo-RBC samples having higher parasitemias
      were cleared faster from the blood circulation of SCID mice. The results suggest
      that the intravascular clearance system in SCID mice may have a mechanism by
      which T. sergenti-parasitized and non-parasitized Bo-RBCs are recognized and
      cleared differentially.

PMID- 8747906
TI  - Identification of an immunodominant 40 kDa merozoite antigen common to the
      Australian T and Dixie vaccine strains of Babesia bovis and the development of
      diagnostic tests specific for these strains.
AB  - Antigenic differences among Australian vaccine and field strains of Babesia bovis
      were investigated in an attempt to identify strain specific antigens. Immunoblots
      revealed substantial differences between the current vaccine strains, designated
      T and Dixie, and previous vaccine strains and field isolates collected on
      properties where vaccination with the T or Dixie strains had failed to provide
      complete protection against tick-borne challenge. A major difference was an
      immunodominant 40 kDa antigen (T40) present in only the T and Dixie strains. The
      molecular weight and immunodominant nature of this antigen suggest that it may be
      the equivalent of the major merozoite surface antigen (MSA-1) described by others
      in North American strains of B. bovis. MSA-1 was shown to be conserved in north
      American isolates but not in an isolate from Israel or in the Australian S and L
      isolates. The work presented here suggests that merozoite surface antigen
      diversity exists among geographically different isolates of B. bovis within
      Australia. Monospecific antiserum to T40 was used to develop an indirect
      fluorescent antibody (IFA) test specific for T and Dixie strain parasites, and a
      blocking enzyme-linked immunosorbent assay (ELISA) specific for antibody to the T
      and Dixie strains. In cases of babesiosis in recently vaccinated cattle, the IFA
      test will be a useful tool for determining whether clinical symptoms are due to a
      severe vaccine reaction or to a concurrent tick-borne infection. In a preliminary
      assessment of potential of the ELISA for the serological identification of
      vaccinated cattle using a total of 160 sera, the test clearly differentiated
      between animals vaccinated with the T or Dixie strains and non-vaccinated
      animals, and was not affected by presence of antibodies to other B. bovis
      strains.

PMID- 8747907
TI  - Ovine toxoplasmosis: seroconversion during pregnancy and lamb birth rate in
      Uruguayan sheep flocks.
AB  - Specific anti-Toxoplasma gondii antibodies were analyzed by latex agglutination
      during the 5 months of pregnancy in the serum of sheep from two flocks in the
      Uruguayan north-west: one flock (79 sheep) kept under an intensive management
      system and the other (494 sheep) kept under an extensive management system.
      Titers obtained using the latex test correlated with those obtained by indirect
      immunofluorescence. Pregnancy was confirmed by laparoscopy in all sheep from the
      smaller flock and by determination of serum progesterone levels in the
      seroconverted sheep from the larger flock. The percentage of sheep originally
      exhibiting significant serum levels of anti-T. gondii antibodies (13.9% in the
      smaller flock and 28.5% in the larger one) as well as the observed levels of
      seroconversion (22.8% and 7.7%, respectively), indicated a high prevalence of
      this infection in the north-west of Uruguay. In addition, birth rates of
      seroconverted sheep in the larger flock were significantly different from those
      of non-seroconverted animals. These results, although preliminary, suggest that
      Toxoplasma infection would produce considerable economic losses in extensive
      ovine production in Uruguay.

PMID- 8747908
TI  - Sarcoptic mange and production performance of swine: a review of the literature
      and studies of associations between mite infestation, growth rate and measures of
      mange severity in growing pigs.
AB  - Cost-effective control of sarcoptic mange requires knowledge of the effects of
      the disease on production. This paper presents a critical review of the
      literature on the association between sarcoptic mange and reduced production
      performance of swine. One of the difficulties in interpreting inconsistent
      findings among studies is lack of information about the severity of disease,
      which is likely to vary considerably. Lack of standard methods and failure to
      quantify disease severity preclude meaningful interpretation of experimental
      results in commercial production. Three experiments with growing pigs were
      conducted to evaluate associations between sarcoptic mite infestation and growth
      rate, and to assess pruritic behaviour and mite-induced lesions at slaughter as
      indices of mange severity. Sarcoptic mange was associated with increased pruritic
      behaviour and the presence of papular dermatitis at slaughter. Pruritic behaviour
      decreased over time despite reinfestation and may be subject to numerous
      behavioural influences. Growth rate tended to be slower in mange infested pigs,
      but a significant effect of mange infestation on average daily gain was found in
      only one trial, in which the severity of skin lesions at slaughter was greatest.
      These observations suggest that the production effects of mange infestation of
      growing pigs are variable. Evaluating dermatitis lesions at slaughter may be an
      objective means for assessing the severity of mange infestation and for relating
      experimental results to commercial swine production.

PMID- 8747909
TI  - Efficacy of injectable doramectin in the therapy and control of Dermatobia
      hominis infestations in Latin America.
AB  - Three studies were conducted in Latin America, one in Brazil, one in Venezuela
      and one in Argentina, using a common protocol to investigate the efficacy of a
      single subcutaneous injection of doramectin at 200 micrograms kg-1 (1 ml per 50
      kg) for the treatment and control of Dermatobia hominis infestations in cattle
      raised under commercial conditions. In each study, two groups of 20 animals each
      were allocated on the basis of D. hominis nodules present 24 h before treatment
      to a treated group (T1), or to a control group (T2) which received saline
      solution at 1 ml per 50 kg of live weight. All cattle were injected in the mid
      dorsal cervical region and examined on treatment day and 2, 7, 15 and 30 days
      post-treatment (p.t.). At each observation day the number of D. hominis nodules
      was counted and the viability of the larvae inside them was assessed and
      recorded. Treatment with doramectin was 100% effective in eliminating D. hominis
      larvae and in controlling the re-establishment of the parasite under field
      conditions of continuous reinfestation. During the first 48 h p.t., dead larvae
      of different ages were found outside or partially outside the nodules in animals
      of the doramectin groups. After 48 h p.t., no live larvae were found inside
      existing nodules, nor did new nodules develop in animals of the doramectin groups
      in any of the three studies. When compared with nodule counts in the control
      group on the same observation day or with parasite burdens on the same animal
      before treatment, doramectin-treated animals began to eliminate parasitic nodules
      at 48 h p.t. Efficacy reached 100% at 7 days p.t. and remained at 100% on
      subsequent observation days (P < 0.05). None of the doramectin-treated animals
      exhibited any clinical signs of adverse reaction to medication.

PMID- 8747910
TI  - Larval salivary gland proteins of the sheep nasal bot fly, (Oestrus ovis L.), are
      major immunogens in infested sheep.
AB  - Tissue extracts from larval instars of the sheep nasal bot, Oestrus ovis, were
      resolved by gel electrophoresis under both native and denaturing conditions.
      Polypeptides resolved under these conditions were tested by immunoblotting
      against sera of infested sheep. Of all tissues examined in this study, salivary
      glands proved to be major immunogens in infested sheep. Salivary gland
      polypeptides were also detected in the washing solution as larval secretory
      products (LSP). To a minor extent, a few polypeptides from the larval cuticle
      were also found to be immunogenic, but they did not contribute to LSP. These
      results were further corroborated by nasal infestation of rabbits that also
      developed specific antibodies against larval salivary gland polypeptides from
      Oestrus ovis.

PMID- 8747911
TI  - Dietary protein for young grazing sheep: interactions with gastrointestinal
      parasitism.
AB  - Effects of protein supplementation and of nematode control on production
      responses in young grazing sheep and on nematode population dynamics were
      assessed. Young Merino wether sheep (n = 270) were allocated to one of three
      supplementation (Su) treatments and one of three regimes of nematode control
      (drench, Dr) in a factorial design. Each of the nine treatments was replicated
      three times in a randomised complete block. Animals received no supplement (Su0)
      or were given supplements at a level equivalent to 200 g day-1, fed three times a
      week. The supplements contained 25% lucerne meal with either 75% sunflower meal
      (Su1) or 75% formaldehyde-treated sunflower meal (Su2). Nematode control regimes
      were: not drenched unless survival of individual animals was threatened (Dr0);
      drenched according to a strategic drenching programme (Dr1); treatment with a
      controlled-release albendazole capsule (Dr2). Infections with Haemonchus
      contortus were suppressed by use of closantel. Due to drought conditions and lack
      of pasture growth, lucerne hay was fed to all sheep from Week 14 onwards (350 g
      per head per day, fed twice a week). Supplementation reduced the need for
      'survival drenching' in Dr0 sheep considerably. Live-weight gain was increased
      significantly by supplementation with Su1 or Su2 during the 36-week experiment.
      Undrenched animals given Su1 or Su2 tended to grow faster than unsupplemented
      animals in the Dr1 and Dr2 groups. Greasy wool production and fibre diameter were
      increased by supplementation and anthelmintic treatment. Faecal worm egg counts
      (FEC) in undrenched sheep were significantly lower for Su1 and Su2 sheep than for
      Su0 sheep. There were no effects of supplementation on FEC in Dr1 or Dr2 sheep.
      Worm burden was generally unaffected by supplementation, while the drenching
      treatments Dr1 and Dr2 reduced worm burden at Week 16 and to a lesser extent at
      Week 27. Trichostrongylus colubriformis was the predominant nematode species,
      with smaller numbers of Nematodirus spp., Trichostrongylus vitrinus,
      Trichostrongylus axei and Ostertagia circumcincta also present. It was concluded
      that supplementary feeding with protein meal substantially reduced production
      losses attributable to nematode infections in young grazing sheep. This appears
      to be due to an enhanced resilience of the host, rather than any major changes in
      development of protective immunity.

PMID- 8747912
TI  - An ivermectin tablet for sheep: efficacy against gastro-intestinal nematodes and
      a bioavailability comparison with a liquid ivermectin formulation.
AB  - An ivermectin tablet for oral administration to sheep was developed for use in
      countries where it is customary to treat sheep with anthelmintic tablets. Tablets
      require no special administration equipment, and offer convenience for storage
      and transport. The ivermectin tablet, which delivers 10 mg of ivermectin (200
      micrograms kg-1 in a 50 kg sheep), had similar bioavailability to a liquid
      formulation of ivermectin (IVOMEC Liquid for Sheep) as determined by peak plasma
      ivermectin concentrations and area under the concentration curve in plasma (P >
      0.10). In dose confirmation trials in which nematode infections were induced in
      helminth-naive sheep, animals treated with the ivermectin tablet had
      significantly fewer adult and fourth-stage larval nematodes than untreated
      control sheep (P < 0.01) with efficacies > 99% against all nematode species
      tested. In six field trials evaluating the efficacy of the ivermectin tablet in
      240 Merino sheep, the reductions in faecal nematode egg counts ranged between 98
      and 100%, as determined by comparison of pre- and post-treatment counts for the
      ivermectin-treated group.

PMID- 8747913
TI  - Evidence for multiple anthelmintic resistance in sheep and goats reared under the
      same management in coastal Kenya.
AB  - Four experiments, two with sheep and two with goats, were carried out to
      determine the efficacy of ivermectin, fenbendazole, levamisole, closantel and
      some of their combinations by faecal egg count reduction tests. In the first
      experiment, injectable ivermectin, oral ivermectin, fenbendazole and levamisole
      were tested in 6-month-old lambs, and their reduction percentages were 77%, 13%,
      42% and 92%, respectively. In the second experiment, with yearling sheep, the
      reduction percentages were 35% for injectable ivermectin, 32% for fenbendazole,
      99% for levamisole, 48% for closantel, 92% for injectable ivermectin combined
      with fenbendazole, 99% for injectable ivermectin combined with levamisole, and
      100% for fenbendazole combined with levamisole. In the study with 18-month-old
      goats given the same dose rates as those recommended for sheep, the reduction
      percentages were 73% for injectable ivermectin, 25% for fenbendazole, and 78% for
      levamisole. Another group of 14-month-old goats was treated with dose rates 1.5
      times those recommended for sheep and the reduction percentages were 93% for
      levamisole, 92% for injectable ivermectin, and 97% for a combination of
      levamisole and ivermectin. In all experiments with sheep and goats the
      gastrointestinal nematode parasites identified by larval cultures were Haemonchus
      contortus, Trichostrongylus spp. and Oesophagostomum spp. The gastrointestinal
      nematodes of both sheep and goats on this farm are resistant to ivermectin and
      fenbendazole, whereas levamisole is still effective in sheep, but not in goats.
      The results are discussed in relation to the farm as a source of breeding stock
      to smallholder farmers and its potential to spread anthelmintic resistance.

PMID- 8747914
TI  - Predacious activity of the nematode-trapping fungus Duddingtonia flagrans against
      cyathostome larvae in faeces after passage through the gastrointestinal tract of
      horses.
AB  - This study was undertaken to examine the potential of the nematode-trapping
      microfungus Duddingtonia flagrans to survive passage through the gastrointestinal
      tract of horses and subsequently to destroy free-living stages of cyathostomes in
      faecal cultures. Three different oral dose levels were tested, two horses being
      used for each level. Faeces were collected twice daily and the numbers of
      parasite eggs per gram of faeces were determined. The numbers of infective third
      stage larvae which developed in faecal cultures were determined after the
      cultures had been incubated for 2 weeks at 24 degrees C. Results showed a
      positive relationship between dose level and reduction in the number of infective
      larvae. Fungi were recovered in faeces at times which corresponded to high larval
      reduction.

PMID- 8747915
TI  - Biological control of trichostrongyles in calves by the fungus Duddingtonia
      flagrans fed to animals under natural grazing conditions.
AB  - The present study was conducted in the 1993 grazing season with yearling calves
      exposed to a pasture with a natural mixed trichostrongyle larval infection. It
      was shown that daily feeding with the microfungus Duddingtonia flagrans during
      the first 2 months of the season led to a lowered herbage infectivity and a
      reduced acquisition of Ostertagia sp. and Cooperia sp. later in the season. In
      addition, the procedure delayed the onset of clinical disease. This was due to
      the nematode-destroying effects of the fungi in the dung excreted by the fungus
      treated calves, as evidenced by results from a parallel in vitro assay on faecal
      larval cultures. The paper discusses future research needs before practical
      biological control can be implemented.

PMID- 8747916
TI  - Studies on multispecific resistance of gastrointestinal nematodes to
      benzimidazoles on dairy-goat farms.
AB  - Multispecific resistance to benzimidazoles was studied in three selected farms.
      These farms had bred dairy goats for more than 15 years. The helminths were
      introduced with the goats at the establishment of the farms which afterwards
      remained isolated. Nematode resistance could then be related to their own
      management practices. Faecal egg count tests and egg hatch assays were performed
      to assess intensity of resistance. The generic (infective larvae in faecal
      cultures) and specific richness (adult worms) were assessed. The resistant
      species were Trichostrongylus colubriformis, Teladorsagia circumcincta,
      Haemonchus contortus and Oesophagostomum venulosum. Faecal egg count reduction
      tests and egg-hatch assays did not match exactly. Faecal larval counts after
      treatments gave a distorted picture of multispecific resistance: Haemonchus and
      Oesophagostomum were very largely over represented. The number of species found
      in the three farms was relatively low compared with other reports in goat farms
      of the area. This reduction of diversity might also be due in part to
      characteristics of breeding management and history (use of permanent pasture and
      introduction of goats at the establishment of farm).

PMID- 8747917
TI  - The combined effect of fenbendazole treatment and a move to aftermath 7 or 9
      weeks after turnout on Dictyocaulus viviparus infections in calves.
AB  - A grazing study was performed with the main objective of examining the effect of
      fenbendazole (FBZ) in a 'dose and move' system on nematode infections in calves
      with special emphasis on Dictyocaulus viviparus. Three groups of six calves were
      grazed from May to October 1993. One group (DM7) was treated with FBZ and moved
      to aftermath (pasture which had only been mown) 7 weeks after turnout. The second
      group (DM9) was similarly treated and moved 9 weeks after turnout and the third
      group served as untreated pasture control group (PC) and was moved to aftermath 9
      weeks after turnout. FBZ treatment removed adult lungworms from DM7 and DM9.
      Tracer calves grazed during the first 7 or the first 9 weeks after turnout
      acquired mean burdens of 18 and 125 lungworms, respectively. In PC faecal larval
      counts increased until the end of August. Most of the animals in this group were
      then suffering from lungworm disease and emergency treatment with ivermectin was
      given. In both FBZ-treated groups, larvae reappeared in the faeces of some of the
      calves 4-5 weeks after treatment. Subsequent reinfection resulted in higher mean
      faecal larval counts in both groups 2 months after treatment, although variation
      in faecal larval counts was high. In DM7 values tended to be higher than in DM9.
      These higher larval counts were associated with mild signs of parasitic
      bronchitis in some calves of DM7, whereas no signs were seen in DM9. At the end
      of the experiment, all calves, and also a group of six permanently housed non
      infected control calves (HC), were infected experimentally with 5000 D. viviparus
      larvae to evaluate development of immunity. The worm counts at necropsy showed
      that all calves on pasture had developed immunity.

PMID- 8747918
TI  - A study of an enzootic focus of sheep babesiosis (Babesia ovis, Babes, 1892).
AB  - Morbidity and mortality due to Babesia ovis in sheep flocks grazing in an
      enzootic area of Israel occur yearly, about 2 weeks after detection of adult
      Rhipicephalus bursa ticks on the animals. Disease incidence peaks in May, but
      lasts throughout the active period of the adult ticks in the spring-summer months
      of April-July. No clinical cases of babesiosis have been registered during the
      active period of the preimaginal stages of R. bursa, from October to February.
      Incidence of parasitaemia during the spring-summer months was variable, ranging
      between 2 and 25%. However, in the winter months the incidence of parasitaemia in
      hoggets increased considerably, reaching 4-60% of the animals. A positive
      serological response to B. ovis was found in 84.5% of the hoggets and 88.9% of
      the ewes. In ewes, the prevalence of the serological response showed no marked
      seasonal variations. Colostral sera of 67.5% and 75% of the ewes and hoggets,
      respectively, were serologically positive for B. ovis. No antibodies were
      detected in the sera of lambs less than 3-4 months of age. The epizootiology of
      sheep babesiosis appears to differ from that of bovine babesiosis.

PMID- 8747919
TI  - Multiple anthelmintic resistance in Haemonchus contortus on a sheep farm in
      India.
AB  - Multiple resistance to benzimidazoles (fenbendazole, albendazole and mebendazole)
      in a strain of Haemonchus contortus in sheep was detected on a farm where
      fenbendazole resistance had already been identified. Following a faecal egg count
      reduction test, this was confirmed by both critical and controlled anthelmintic
      tests. Different groups of sheep infected naturally or given an experimental
      infection with the fenbendazole-resistant strain were treated with the
      recommended doses of various anthelmintics. Compared to the control group,
      percentage reductions in faecal egg counts of sheep treated with fenbendazole,
      albendazole, mebendazole, levamisole and morantel varied between 56% and 81% and
      worm counts between 71% and 86%. The results indicate the presence of multiple
      anthelmintic resistance in this strain of H. contortus on this farm. Sheep
      treated with ivermectin and closantel showed 100% reductions in faecal egg and
      worm counts, suggesting high efficacy of these drugs against the population of H.
      contortus on this farm.

PMID- 8747920
TI  - New seizure frequency QTL and the complex genetics of epilepsy in EL mice.
AB  - EL/Suz (EL) mice experience recurrent seizures that are similar to common partial
      complex epilepsy in humans. In the mice, seizures occur naturally at 90-100 days
      of age, but can be induced in younger mice and analyzed as a semi-quantitative
      trait after gentle rhythmic stimulation. A previous genetic mapping study of EL
      backcrosses to the strains ABP/LeJ or DBA/2J showed two quantitative trait loci
      (QTL) with large effects on seizure frequency (El1, Chr 9; El2, Chr 2) and
      implied the existence of other QTL with lesser effects. To further the
      understanding of EL-derived seizure alleles, we examined intercross progeny of EL
      and the strains ABP/LeJ and DDY/Jcl, and also a backcross of (EL x DDY)F1 hybrids
      to DDY. A new large-effect seizure frequency QTL was found (El5, Chr 14), a more
      minor QTL confirmed (El3, Chr 10), and two additional QTL proposed (El4, Chr 9;
      El6, Chr 11). The serotonin receptor gene, Htr2a, maps near and is a candidate
      for El5, and linkages of other serotonin receptor genes to seizure frequency QTL
      are noted. In addition, a strong gender effect was revealed, and epistasis was
      found between Chr 9 and Chr 14 markers. Despite this progress, however, our
      results revealed a more complex determinism of epilepsy in EL mice than
      previously described. In particular, no single El locus or pair was essential for
      frequent seizures, as QTL with large effects, such as El5, El2, and El1, were
      highly dependent on genetic context. Our studies highlight the importance of gene
      interaction in some complex mammalian traits defined by natural variation.

PMID- 8747921
TI  - Congenic strains reveal effects of the epilepsy quantitative trait locus, El2,
      separate from other El loci.
AB  - Congenic mouse strains made by transferring epilepsy predisposing alleles El1,
      El2, and El3 from the EL/Suz strain to the ABP/Le recipient were tested for
      seizure frequency following gentle rhythmic stimulation. Mice homozygous for El2,
      but not El1 or El3, experienced seizures much more frequently than ABP controls,
      while respective El1 homozygotes and El2 heterozygotes had only a modest increase
      over ABP, and El3 homozygotes showed no increase. Association between marker
      genotypes and seizure frequency in small intra-strain crosses showed that the
      phenotypic effects of El2 map to the selected interval, and that segregation of
      El2 accounts for virtually all genetic effects. However, in separating El2 from
      other EL susceptibility alleles, the seizure frequency phenotype was weaker and
      less heritable than in crosses between parental strains. These results confirm
      El2 as an important QTL and show that it has significant phenotypic effects in
      the absence of other EL-derived alleles, including El1. In addition, the present
      localization of El2 on Chr 2 suggests several potential candidate genes for El2,
      including the beta subunit of phospholipase-C. The approach to dissecting complex
      traits by making congenic strains for individual QTL is discussed.

PMID- 8747922
TI  - Disruption of murine Hexa gene leads to enzymatic deficiency and to neuronal
      lysosomal storage, similar to that observed in Tay-Sachs disease.
AB  - Tay-Sachs disease is an autosomal recessive lysosomal storage disease caused by
      beta-hexosaminidase A deficiency and leads to death in early childhood. The
      disease results from mutations in the HEXA gene, which codes for the alpha chain
      of beta-hexosaminidase. The castastrophic neurodegenerative progression of the
      disease is thought to be a consequence of massive neuronal accumulation of GM2
      ganglioside and related glycolipids in the brain and nervous system of the
      patients. Fuller understanding of the pathogenesis and the development of
      therapeutic procedures have both suffered from the lack of an animal model. We
      have used gene targeting in embryonic stem (ES) cells to disrupt the mouse Hexa
      gene. Mice homozygous for the disrupted allele mimic several biochemical and
      histological features of human Tay-Sachs disease. Hexa-/- mice displayed a total
      deficiency of beta-hexosaminidase A activity, and membranous cytoplasmic
      inclusions typical of GM2 gangliosidoses were found in the cytoplasm of their
      neurons. However, while the number of storage neurons increased with age, it
      remained low compared with that found in human, and no apparent motor or
      behavioral disorders could be observed. This suggests that the presence of beta
      hexosaminidase A is not an absolute requirement of ganglioside degradation in
      mice. These mice should help us to understand several aspects of the disease as
      well as the physiological functions of hexosaminidase in mice. They should also
      provide a valuable animal model in which to test new forms of therapy, and in
      particular gene delivery into the central nervous system.

PMID- 8747923
TI  - The SMXA: a new set of recombinant inbred strain of mice consisting of 26
      substrains and their genetic profile.
AB  - A new set of recombinant inbred (RI) strain SMXA consisting of 26 substrains was
      established between SM/J and A/J. The history of the SMXA RI strains and their
      genetic profile covering 158 genetic marker loci are reported. From the strain
      distribution pattern among SMXA RI strains, the chromosomal location of salivary
      and tear protein genes Spe1-r, Spe1-s, Spe2, and Tpe1 were newly determined.

PMID- 8747924
TI  - Sequence characterization of ENU-induced mutants of glucose phosphate isomerase
      in mouse.
AB  - Four of five mutations producing GPI1 null lethal phenotypes in the homozygous
      state, which were previously identified from the offspring of male mice,
      spermatogonially treated with N-ethyl N-nitrosourea (ENU), have been
      characterized at the nucleotide level by reverse transcription of RNA from
      heterozygotes for mutant and wild-type alleles and cycle sequencing with cDNA
      derived primers. In three of the mutations studied, a single nucleotide
      substitution, altering the predicted amino acid on translation, was observed in
      the mutant allele. In Gpi1-sam1H amino acid residue 277, TCA Ser (wild type), is
      altered to CCA Pro, and in Gpi1-sbm3H and Gpi1-sbm4H amino acid residue 510 Asp
      GAC (wild type) is altered to GGC Gly. These ENU-induced mutations occur at A-T
      base pairs in agreement with the current view of the mechanism of action for this
      mutagen. These changes also occur at residues implicated as being important in
      the catalytic functioning of the enzyme, from crystallographic studies, and may
      explain the loss of enzyme function. The fourth identified mutation, Gpi1-sbm2H,
      is a deletion of amino acid residues Arg134 to Leu162 inclusive, which may arise
      from incorrect splicing of mRNA; a fifth mutation has remained undetermined.

PMID- 8747925
TI  - Thirteen loci physically assigned to sheep chromosome 2 by cell hybrid analysis
      and in situ hybridization.
AB  - Sheep x hamster cell hybrids containing sheep metacentric Chromosome (Chr) 2 were
      produced by fusing blood leukocytes from normal sheep with hamster auxotrophic
      Ade F-minus mutants. Cell clones that were isocitrate dehydrogenase 1 (IDH1)
      positive were cytogenetically characterized, confirming that they contained sheep
      Chr 2. The following loci were newly assigned by Southern hybridization to sheep
      Chr 2: lipoprotein lipase (LPL), glycoprotein-4-beta galactosyltransferase 2
      (GGTB2), neurofilament light polypeptide (68 kDa; NEFL), surfactant-associated
      protein 2 (SFTP2), lymphocyte-specific protein tyrosine kinase (LCK), and nebulin
      (NEB). These new assignments and the in situ localization of gelsolin (GSN) to
      sheep Chr 2pter-p24 are consistent with the predicted homology of cattle Chr 8
      (U18) with sheep Chr 2p, and of cattle Chr 2 (U17) with sheep 2q. In addition,
      the assignment by cell hybrid analysis of loci previously mapped to Chr 2 in
      sheep, viz., cholinergic receptor, nicotinic, delta polypeptide (CHRND), collagen
      type III alpha 1 (COL3A1), fibronectin 1 (FN1), isocitrate dehydrogenase (IDH1),
      and villin 1 (VIL1), confirmed the localization of sheep syntenic group U11 to
      this chromosome. By nutritional selection and complementation of the hamster
      auxotrophic Ade F mutation, the multifunctional enzyme locus
      phosphoribosylaminoimidazolecarboxamide formyltransferase (AICAR
      transformylase)/IMP cyclohydrolase (inosinicase) (provisionally given the symbol
      PRACFT) has also been newly assigned to sheep Chr 2. This report significantly
      extends the number of loci physically mapped to sheep Chr 2 and confirms its
      close homology with cattle Chrs 2 and 8.

PMID- 8747926
TI  - Strain distribution pattern for SSLP markers in the SWXJ recombinant inbred
      strain set: chromosomes 1 to 6.
AB  - We typed 147 simple sequence length polymorphisms in the SWXJ recombinant inbred
      (RI) strain set spanning Chromosomes (Chrs) 1-6. The strain distribution pattern
      for these loci was combined with data from 18 previously typed loci for SWXJ,
      resulting in new chromosome maps for this RI set, with an average density of 3.5
      cM between loci. This is the first systematic effort to develop a more highly
      resolved genetic map for the SWXJ RI set and thereby improves the usefulness of
      this genetic tool for mapping genes underlying both simple and complex genetic
      disorders.

PMID- 8747927
TI  - Monitoring the efficacy of hybrid selection during positional cloning: the search
      for BRCA1.
AB  - Positional cloning often requires isolation of candidate genes from a large,
      genetically defined region. Hybrid selection (direct cDNA selection, solution
      hybrid capture) is a rapid, simple procedure that has been used to identify
      expressed sequence tags (ESTs) from cloned genomic DNA. We used hybrid selection
      to screen a 600-kb region that includes the BRCA1 gene. From a set of 931
      sequenced clones, we obtained 118 nonoverlapping candidate ESTs from ovary and
      lymphocyte cDNA. We analyzed the results of our hybrid selection experiments with
      particular attention to the overall completeness, efficiency, and background
      noise of the experiment. We introduce simple parameters that serve as measures of
      important aspects of the hybrid selection process in the context of positional
      cloning.

PMID- 8747928
TI  - Genetic mapping of five mouse genes encoding synaptotagmins.

PMID- 8747929
TI  - Assignment of three loci: tumor suppressor protein-53 (TP53), retinoic acid
      receptor A (RARA), collagen 1A1 (COL1A1) to Syrian hamster chromosome 9. Evidence
      that this chromosome is homologous with human chromosome 17, mouse chromosome 11,
      and rat chromosome 10.

PMID- 8747930
TI  - Analysis of mammalian MUC1 genes reveals potential functionally important
      domains.

PMID- 8747931
TI  - Localization of a Na+,K(+)-ATPase alpha 2 subunit gene, Atp1a2, on rat chromosome
      13.

PMID- 8747932
TI  - Selective assessment of in vitro radiosensitivity of tumour cells and fibroblasts
      from single tumour biopsies using immunocytochemical identification of colonies
      in the soft agar clonogenic assay.
AB  - The assumed selective growth of tumour cells has formed the basis for the use of
      the soft agar clonogenic assay to test in vitro radio- and chemosensitivity of
      tumours. However, recent studies have demonstrated that fibroblasts proliferate
      in soft agar in addition to tumour cells. The present study was initiated to
      quantify the contaminating growth of non-malignant cells in the modified form of
      the Courtenay-Mills soft agar assay, in order to establish a reliable assay for
      estimating tumour cell radiosensitivity in squamous cell carcinomas of the head
      and neck. DNA flow cytometry analysis confirmed that 'tumour fibroblasts'
      (fibroblasts obtained from tumour biopsies) grow in soft agar. In contrast, white
      blood cells did not form colonies. Different media were tested with soft agar,
      but a selective medium for tumour cells was not found. Therefore, a colony filter
      technique combined with an immunocytochemical analysis was developed to quantify
      the number of tumour cell and fibroblast colonies. In 12 tumour biopsies, 2-33%
      of the colonies were Cytokeratin AE1-3 positive, whereas 83-100% of the colonies
      were 5B5 fibroblast antibody positive. The parameter normally reported, the
      overall SF2 (surviving cell fraction at 2 Gy) based on colonies in agar, was
      found to be statistically significantly correlated to the fibroblast SF2, but not
      to the tumour cell SF2. The overall SF2 was significantly different from the
      tumour cell SF2 in half of the tumours. Furthermore, the tumour cell SF2 was not
      correlated to fibroblast SF2. In consequence of our findings, correcting for
      fibroblast contamination is a necessity, when studying in vitro sensitivity of
      tumour cells. Combining the soft agar clonogenic assay with the new colony filter
      technique and the immunocytochemical analysis appear to be useful for making this
      routine correction and for measuring the in vitro radiosensitivity of both tumour
      cells and fibroblasts from single tumour biopsies, which is of interest in future
      clinical studies on predictive assays.

PMID- 8747933
TI  - Effects of stimulated repopulation on oral mucositis during conventional
      radiotherapy.
AB  - The effect of local conditioning of human oral mucosa by silver nitrate solution
      (3%) on epithelial proliferation rates was tested in 11 healthy volunteers by in
      vitro labelling of biopsies with tritiated thymidine. Compared to control
      biopsies from 13 volunteers, stimulation over 3 days, 3 times per day, yielded a
      significant (p = 0.006) increase in the epithelial labelling index (LI) from 4.75
      +/- 0.32% to 6.85 +/- 0.65%, i.e., by 44%. The increase in the absolute number of
      labelled cells per mm epithelial length was dependent on the overall cell density
      at the various intraoral sites and varied between 45% in the maxillary vestibule
      and 91% at the floor of the mouth. In an analysis of variance, stimulation turned
      out to be the most important source causing the effect (p = 0.011 for LI and
      0.015 for labelled cells per mm). In a radiotherapy trial with conventional
      postoperative treatment with 5 x 2 Gy/week to a total dose of 60 Gy in 6 weeks,
      the left buccal mucosa in 10 patients with squamous cell carcinomas of the head
      and neck was conditioned (3% silver nitrate, 3 times per day, 5 days before and
      the first 2 days of radiotherapy) while the contralateral mucosa, receiving an
      identical dose, served as individual control. Mucositis scores according to the
      EORTC/RTOG or the Dische system showed that the time course and severity of the
      mucosal response was almost identical in both cheeks, which is in clear contrast
      to a previous clinical study (Maciejewski et al. Radiother. Oncol. 22, 7-11,
      1991). Differences in radiation dose intensity, i.e., weekly dose, in these
      studies are discussed as a tentative explanation for the different clinical
      findings.

PMID- 8747934
TI  - Fractionated stereotactic radiotherapy with the Leksell Gamma Knife: feasibility
      study.
AB  - The main aim of this study was to check feasibility of stereotactic radiotherapy,
      which is routinely practised on linear accelerators, using a fixed Leksell
      stereotactic frame and a Leksell Gamma Knife. The study refers to the first
      experiences with 48 patients treated by a fractionated regimen (in 2-6 days).
      Isoeffect relationships calculations based on the linear-quadratic model and the
      levels of applied radiation doses, taking into account radiobiology of the
      tumour, tumour volume, critical structures surrounding the treated lesion and
      other factors are discussed. The procedure for quality control during the whole
      fractionated regimen is described. The study has shown that stereotactic
      radiotherapy with the Leksell Gamma Knife is feasible. However, only early
      effects can be discussed and there are still questions remaining which should be
      carefully studied: tolerance doses for critical structures at fractionation,
      definition of an 'ideal' fractionation regimen, and justification of the linear
      quadratic model in the case of stereotactic radiotherapy.

PMID- 8747935
TI  - Micronucleus induction in 10 human tumour cells after high- and low-dose
      radiation.
AB  - A number of data measuring survival of animal or human cells to low LET ionizing
      radiation have demonstrated that these cells may be hypersensitive to doses below
      1 Gy, possibly due to the absence of an inducible repair mechanism, which is
      observed at higher doses. The production of micronuclei (MN) in cells exposed to
      ionizing radiation reflects genotoxic damage. Moreover, the micronucleus assay is
      sensitive to low radiation doses. We have exposed 10 human tumour cell lines to
      doses ranging between 0.12 and 4 Gy. Using cytochalasin B to block the cells in a
      binucleate phase, we have scored the fraction of binucleate cells (BNC)
      expressing MN, as well as the number of MN per BNC, as a function of gamma-ray
      dose. Experimental points were fitted with a binomial equation. Doses from 1 to 4
      Gy were fitted separately from those below 1 Gy, and the initial slopes after
      both fits were compared. Taken together, the initial slopes of MN induction after
      low-dose (LD) irradiation were not different from those after high-dose (HD)
      irradiation. Only in one cell line was a significant increase in MN production
      detected after LD irradiation. This cell line had the shallowest linear term
      after HD irradiation. It appeared that the likeliness of expressing
      hypersensitivity at LD was correlated with the quadratic term of MN induction at
      HD, which does not contradict an inducible repair hypothesis. However, the
      failure of observation of a significant hypersensitivity at LD for nine cell
      lines, and the high variability of response at LD suggests that this occasional
      effect may be influenced by other factors as well.

PMID- 8747936
TI  - The influence of intravesical photodynamic therapy on subsequent bladder
      irradiation tolerance.
AB  - The aim of this project was to measure the irradiation tolerance of normal (non
      tumour bearing) mouse bladder after previous intravesical photodynamic therapy
      (PDT). Illumination with a range of light doses at 24 h after Photofrin was used
      as the initial PDT treatment and irradiation with a range of X-ray doses was
      given at 12 or 24 weeks after the initial therapy. Functional bladder damage was
      assessed from changes in micturition frequency (tested regularly for a follow-up
      period of 53 weeks after irradiation) and from cystometry measurements of the
      bladder at 53-56 weeks. PDT alone caused a marked increase in micturition
      frequency, with (partial) recovery by the time of irradiation. Irradiation alone
      caused a modest, transient acute response within 5 weeks and a progressive,
      permanent late response starting from about 25 weeks depending on X-ray dose. A
      reduced bladder capacity was also evident at 53-56 weeks after 20 Gy X-rays and
      after PDT alone. Irradiation after previous intravesical PDT caused an acute
      reaction similar to X-rays alone, but there was a much earlier expression of late
      functional bladder damage. The final level of damage prior to sacrifice at 53-56
      weeks, was not significantly greater than after X-rays alone. These results
      suggest that irradiation after previous whole bladder PDT, for refractory bladder
      tumours, may lead to an increased risk of persistent increases in micturition
      frequency and reduced bladder capacity, beginning at very early times after
      irradiation.

PMID- 8747937
TI  - The importance of fluence rate in photodynamic therapy: is there a parallel with
      ionizing radiation dose-rate effects?
AB  - Several similarities can be found between dose-rate effects in radiotherapy and
      fluence-rate effects in photodynamic therapy (PDT). At low dose rates repair of
      sublethal damage can occur, whereas at high dose rates oxygen depletion can
      decrease the effects of both therapies. The available literature for fluence-rate
      effects in PDT is discussed here in relation to therapeutic implications.

PMID- 8747938
TI  - Cell loss factors and the linear-quadratic model.
AB  - A method is described for incorporating a variable cell loss factor (phi) within
      the linear-quadratic (LQ) model. By allowing for a progressive reduction in phi
      as treatment progresses, the revised model behaves in a way which is consistent
      with the apparent presence of accelerated tumour repopulation during fractionated
      radiotherapy. Predictions based on a slowing of the cell loss process, rather
      than a true increase in clonogen proliferation rate, are consistent with the
      phenomenon of 'unmasking' of potential doubling time described by Fowler (Fowler,
      J.F. Rapid repopulation in radiotherapy: a debate on mechanism. Radiother Oncol
      24: 125, 1992). An optional time delay factor may be included, to allow for the
      fact that progressive reduction in cell loss may not begin until part of the
      treatment has been delivered. The model provides a description of the manner in
      which tumour control doses are likely to increase as overall treatment time is
      increased.

PMID- 8747939
TI  - Optimization of intensity-modulated 3D conformal treatment plans based on
      biological indices.
AB  - To overcome the limitations of the intensity modulation optimization techniques
      based on dose criteria, we introduce a method for optimizing intensity
      distributions in which we employ an objective function based on biological
      indices. The objective function also includes constraints on dose and dose-volume
      combinations to ensure that the results are consistent with the physician's
      judgement. We apply a variant of the steepest-descent method to optimize the
      objective function. The method is three-dimensional and incorporates scattered
      radiation in the optimization process using an iterative scheme employing the
      pencil beam convolution method. Previously we had shown that the inverse
      technique of obtaining optimum intensity distributions, for which the objectives
      are defined in terms of a desired uniform dose to the target volume and desired
      upper limits of dose to normal organs, produces satisfactory approximations of
      the desired dose distributions for prostate plans. However, for lung, the
      performance of this technique was considerably inferior. Our conclusion was that,
      in general, it is not sufficient to specify the objectives of optimization purely
      in terms of a desired pattern of dose and that the objectives should also
      incorporate biology, perhaps in the form of biological indices. We demonstrate
      that the biology-based approach produces lung plans that are superior to those
      produced when only dose-based objectives are used. For the treatment of prostate,
      the two methods produce comparable dose distributions.

PMID- 8747940
TI  - Setup deviations in wedged pair irradiation of parotid gland and tonsillar
      tumors, measured with an electronic portal imaging device.
AB  - The first aim of this study was to quantify estimated translational setup
      deviations of patients treated with a wedged pair of oblique beams for parotid
      gland and tonsillar tumors, using portal imaging. The second aim was to design an
      off-line setup verification procedure, to improve the setup accuracy, if
      necessary. Thirty-one patients were treated with two conformal fields (anterior
      oblique and posterior-oblique). The patients were immobilized with a head cast.
      For the last 10 patients, the rigidity of the cast was improved while, in
      addition, wax molds with metal markers were placed into the outer ear for image
      correlation. Portal images were acquired about weekly. Setup deviations were
      analyzed, using anatomical structures and, when available, metal markers for
      image matching. The consistency of the deviations was determined by the
      correlation between deviations in the cranio-caudal direction, as measured from
      both beams. When the deviations were consistent, the translational setup
      deviation during a treatment session could be described by a three-dimensional
      (3D) vector. A setup verification procedure was designed using a computer
      simulation. The statistics of the 3D setup deviations were used as input. The
      output consisted of the resulting setup accuracy and workload (i.e., the number
      of setup corrections and portal images). Using the anatomical structures for
      image correlation, the deviations in the cranio-caudal direction were not
      correlated, either for the old or the improved cast. However, by using the metal
      markers, the deviations were correlated and a 3D analysis could be performed. The
      standard deviations, averaged over the three directions, were equal to 1.8 and
      1.4 mm for the distribution of systematic and random deviations, respectively.
      Application of a setup verification procedure, with 0.7 corrections on the
      average per patient, could potentially reduce the percentage of 3D systematic
      deviations larger than 4 mm from 30 to 2%. It can be concluded that it was not
      possible to obtain consistent translational setup deviations, due to rotations.
      To quantify 3D translational setup deviations, it was necessary to use additional
      metal markers, which were visible in the portal images of both beams. A further
      improvement of the setup accuracy is possible by using an off-line setup
      verification procedure.

PMID- 8747941
TI  - Hemipelvectomy and intraoperative radiotherapy for bone and soft tissue sarcomas
      of the pelvic girdle.
AB  - Current treatment of locally advanced bone and soft tissue sarcomas of the pelvic
      girdle are associated with a high local and distant failure rate, and local tumor
      control after hemipelvectomy can be a significant problem. IORT has been used in
      conjunction with hemipelvectomy, both conventional (seven patients) and limb
      sparing internal hemipelvectomy (one patient), in seven males and one female,
      median age 27 (range 24-57) years with locally extensive high grade bone (seven
      patients) or soft tissue (one patient) sarcomas. IORT (15-30 Gy, 8-16 MeV) was
      delivered to sacral resection margins and surrounding soft tissues considered
      likely to harbor microscopically residual disease. Four patients received 46-54
      Gy postoperative radiotherapy in addition to IORT. During a median follow-up of
      33 months (range 6-131 months) two patients developed a local recurrence (25%),
      and five patients distant metastases (62%). Three patients with pelvic girdle
      sarcomas remained free of tumor (37%) with a mean follow-up of 100 (range 49-131)
      months. There was no treatment-related mortality. Two patients developed
      radiation-induced necrosis of the coccyx (25%). On the basis of this preliminary
      experience, it appears that IORT may substantially help to control local
      recurrence and survival in patients with marginally resectable sarcomas of the
      pelvic girdle after hemipelvectomy. Since the majority of the patients die from
      metastatic disease, there is a need for adjuvant systemic treatment.

PMID- 8747942
TI  - Low-dose radiotherapy for stage I seminoma: early results.
AB  - One hundred and one patients with stage I seminoma were irradiated with total
      doses of 30, 25.5 and 20 Gy to gradually reduced target volumes (paraaortic,
      pelvic, and inguinal regions to paraaortic only). Low doses and small target
      volumes resulted in excellent survival and freedom of recurrence but in more
      frequent nausea.

PMID- 8747943
TI  - Peroperative brachytherapy with the use of a vicryl mat in advanced or recurrent
      pelvic tumors.
AB  - Uncontrolled tumor growth of pelvic tumors is a very serious problem. To test the
      possibility of combining intra-operative placement of brachytherapy catheters
      fixed in a vicryl mat, patients with pelvic tumors were subjected to surgery
      followed by brachytherapy plus external radiotherapy. IN CONCLUSION: the
      procedure is feasible.

PMID- 8747944
TI  - Re: late effects toxicity scoring.

PMID- 8747945
TI  - Analysis of 561 patients with 690 middle cerebral artery aneurysms: anatomic and
      clinical features as correlated to management outcome.
AB  - In a series of 1314 consecutive patients with cerebral aneurysms from a defined
      catchment area in eastern Finland (870,000 inhabitants), 561 patients (43%) had
      middle cerebral artery aneurysms (MCAAs). One or more associated aneurysms were
      common; 221 patients with MCAAs (39%) had multiple intracranial aneurysms (MIA).
      In other words, three-fourths (73%) of all patients with MIA had at least one
      MCAA. Multiple MCAAs, found in 111 patients (20%), were common in this Finnish
      population. One hundred of these patients had bilateral MCAAs, of whom 63 had
      mirror aneurysms, that is, aneurysms at the same site but on different sides.
      Thirty-five patients had "pure" mirror aneurysms, that is, they did not have any
      other aneurysms. Most MCAAs (81%) were located at the bifurcation. Three-fourths
      (72%) of the proximal MCAAs were associated with MIA. Giant aneurysms were
      significantly more common as single MCAAs than as any other single aneurysm. The
      frequency of intracerebral hematomas (42%) was by far higher in patients with
      MCAAs than in patients with ruptured aneurysms at other sites. Most of the
      intracerebral hematomas occurred in patients with bifurcation MCAAs that pointed
      laterally. Patients with MCAAs had surprisingly bad management outcomes despite
      good surgical results in patients with good Hunt and Hess grades. There were
      significantly more poor outcomes (Glasgow Outcome Scale score, 3-5) among
      patients with ruptured MCAAs than among those with any other anterior circulation
      aneurysms (32 and 25%, respectively). Also, the multiplicity of aneurysms
      increased the risk for poor outcome, which occurred in 39% of the patients who
      had MIA with one MCAA and 37% of those who had multiple MCAAs. Epilepsy, severe
      hemiparesis, and visual field deficits were the most common disabilities in long
      term survivors, associated far more frequently with MCAAs than with aneurysm at
      other sites.

PMID- 8747946
TI  - Intracerebral microdialysis of glutamate and aspartate in two vascular
      territories after aneurysmal subarachnoid hemorrhage.
AB  - Cerebral ischemia associated with subarachnoid hemorrhage may have severe
      consequences for neuronal functioning. The excitatory amino acid
      neurotransmitters glutamate and aspartate have been shown to be of particular
      importance for ischemia and ischemic neuronal damage. For seven patients who
      underwent early surgery for ruptured intracranial aneurysms, intracerebral
      microdialysis of glutamate and aspartate was performed to monitor local metabolic
      changes in the medial temporal (all seven patients) and subfrontal cortex
      (Patients 4 through 7). Samples were collected every 30 or 60 minutes, using an
      autosampler. The results show that extracellular glutamate and aspartate
      concentrations can rise to very high levels after surgery for subarachnoid
      hemorrhage and aneurysm. These increased levels of excitatory amino acids
      correlated well with the clinical course and neurological symptoms of the
      patients. Simultaneous sampling from two vascular territories (middle cerebral
      artery and anterior cerebral artery) also showed that a rise in extracellular
      glutamate and aspartate in one territory is not necessarily parallel with a rise
      in the other. The application of the microdialysis technique with an on-line
      assay system might be of value in the future for continuous monitoring of
      ischemic events to optimize treatment with, for example, blockers of
      glutamatergic neurotransmission.

PMID- 8747947
TI  - Continuous monitoring of partial pressure of brain tissue oxygen in patients with
      severe head injury.
AB  - Ischemia is one of the major factors causing secondary brain damage after severe
      head injury. We have investigated the value of continuous partial pressure of
      brain tissue oxygen (PbrO2) monitoring as a parameter for cerebral oxygenation in
      22 patients with severe head injury (Glasgow Coma Scale score, < or = 8). Jugular
      bulb oxygenation, intracranial pressure, and cerebral perfusion pressure were
      simultaneously recorded. O2 and CO2 reactivity tests were performed daily to
      evaluate oxygen autoregulatory mechanisms. PbrO2 monitoring was started an
      average of 7.0 hours after trauma with a mean duration of 74.3 hours. No
      complications were seen, and the calibration of the catheters after measurement
      showed a zero drift of 1.2 +/- 0.8 mm Hg and a sensitivity drift of 9.7 +/- 5.3%.
      In 86% of patients, PbrO2 was < 20 mm Hg in the acute phase. Mean PbrO2
      significantly increased during the first 24 hours after injury. Two distinct
      patterns of change of PbrO2 over time were noted. The first pattern was
      characterized by normal stable levels after 24 hours, and the second was
      characterized by transiently elevated levels of PbrO2 during the second and third
      days. PbrO2 values < or = 5 mm Hg within 24 hours after trauma negatively
      correlated with outcome. O2 reactivity was significantly lower in patients with
      good outcomes. CO2 reactivity showed no constant pattern of change over time and
      was not correlated with outcome. Increased hyperventilation was shown to decrease
      PbrO2 in some patients. Accurate detection of the moment of cerebral death was
      possible on the basis of the PbrO2 measurements. The correlation between PbrO2
      and other parameters, such as intracranial pressure and cerebral perfusion
      pressure, was weak. We conclude that PbrO2 monitoring is a safe and clinically
      applicable method in patients with severe head injury. The early occurrence of
      ischemia after head injury can be monitored on a continuous basis. Deficiency of
      oxygen autoregulatory mechanisms can be demonstrated, and their occurrence is
      inversely related to outcome. For practical clinical use, the method seemed to be
      superior to jugular oximetry.

PMID- 8747948
TI  - Intramedullary spinal cord tumors in neurofibromatosis.
AB  - Neurofibromatosis (NF) describes the most commonly inherited disorders affecting
      the nervous system. These autosomal dominant, neurocutaneous syndromes are
      associated with multiple tumors of the nervous system, including neurofibromas,
      schwannomas, meningiomas, and intracranial gliomas. Spinal cord involvement in NF
      is typically from extramedullary growth of spinal nerve root tumors.
      Intramedullary spinal cord tumors in NF have been reported as scattered, single
      cases in literature. However, this association has not been clearly defined as
      have other nervous system neoplasms that are typically linked with NF. We present
      a series of nine patients with NF with intramedullary spinal cord tumors who were
      managed at our institution from 1984 to 1994. The patients' ages ranged from 4 to
      31 years. There were seven male patients and two female patients. Three patients
      had NF-1 (von Recklinghausen's), five patients had NF-2, and one patient had NF,
      type uncertain. There were three cervicomedullary tumors, two cervical tumors,
      three cervicothoracic tumors, and one thoracic tumor. A histological examination
      revealed five ependymomas, three astrocytomas, and one intramedullary schwannoma.
      Two patients with malignant intramedullary spinal ocrd tumors have died with
      progressive disease. One other patient has required a subsequent operation for
      recurrent tumor. The other six patients are doing well, and their prognosis is
      expected to be related to their systemic disease. We conclude that there is a
      clinical entity of intramedullary spinal cord tumors associated with NF.

PMID- 8747949
TI  - Fractured odontoid: the management of delayed neurological symptoms.
AB  - Undiagnosed and untreated odontoid fractures are relatively common in developing
      countries where treatment for minor injuries is not considered. As a result,
      patients frequently present with neurological deterioration secondary to delayed
      odontoid dislocation. Fifty-one consecutive patients with this problem were
      entered into a management protocol and reviewed for this report. After diagnosis,
      reducibility was analyzed by extension films, and all patients who could not be
      reduced were initially managed in cranial long traction. Thirty-seven were
      reduced spontaneously or by traction alone, and 12 required transoral
      decompression. All underwent posterior C1-C2 fusion. Postoperatively, all were
      treated in external orthoses. The neurological recovery was excellent in 34
      patients. Seven patients could function but had some disability, three patients
      had disabling spasticity, and three remained bedridden. Four deaths occurred as a
      result of respirator-dependent patients being taken home for social and financial
      reasons. As a result of this case-controlled study, we recommend that the
      treatment protocol first analyze reducibility by extension x-rays and then try
      traction for as long as 14 days to attempt reduction in patients who did not
      reduce in extension. Failure of reduction is indication for transoral
      decompression, and all patients require C1-C2 fusion. The neurological recovery
      is related to initial impairement but can be satisfactory in > 75% of patients.

PMID- 8747950
TI  - Injuries involving the transverse atlantal ligament: classification and treatment
      guidelines based upon experience with 39 injuries.
AB  - Comprehensive anatomic and clinical analyses of 39 patients with injuries
      involving the transverse atlantal ligament or its osseous insertions were
      performed to assess the morphology of the injured ligaments and the patients'
      capacity to heal. Injuries of the upper cervical spine were screened with plain
      radiographs, thin-section computed tomography, and magnetic resonance imaging
      studies. The injuries were classified as disruptions of the substance of the
      ligament (Type I injuries, n = 16) or as fractures and avulsions involving the
      tubercle for insertion of the transverse ligament on the C1 lateral mass (Type II
      injuries, n = 23). These two types of injuries had distinctly different clinical
      characteristics that were useful for determining treatment. Type I injuries were
      incapable of healing satisfactorily without internal fixation; they should be
      treated with early surgery. Type II injuries, which rendered the transverse
      ligament physiologically incompetent even though the ligament substance was not
      torn, should be treated initially with a rigid cervical orthosis, because they
      had a 74% success rate nonoperatively. Surgery should be reserved for patients
      with Type II injuries that have nonunion with persistent instability after 3 to 4
      months of immobilization. Type II injuries had a 26% rate of failure of
      immobilization; therefore, close monitoring is needed to detect patients who will
      require delayed operative intervention.

PMID- 8747951
TI  - Prospective analysis by computed tomography and long-term outcome of 23 adult
      patients with chronic idiopathic hydrocephalus.
AB  - From 1986 to 1989, 23 adult patients (average age, 70 yr) with idiopathic chronic
      hydrocephalus received shunts with medium-pressure Pudenz-Schulte valves for
      suspected normal pressure hydrocephalus. Prospective clinical and computed
      tomographic monitoring was continued for at least 5 years. We observed the
      formation of a hypodense subdural collection in each of 10 patients (43%). Those
      collections that occurred early, i.e., within the first 9 postoperative days,
      evolved differently from those that occurred late; only early hypodense
      collections became subdural hematomas (three cases). In one case, a subdural
      hematoma was already present 9 days after surgery, so that four patients (17%)
      presented a subdural hematoma within the first 2 postoperative months. Our long
      term follow-up revealed three patients (13%) with hypodense subdural collections,
      which appeared more than 2 months after surgery. None of the collection evolved
      into a subdural hematoma. Thirteen patients (57%) died between 9 and 68 months
      (average, 20 mo) after surgery, most often of an ischemic stroke. During the 1st
      postoperative year, there was improvement in the condition of 22 patients (96%)
      who had received a ventricular shunt; 21 of these patients (91%) remained
      improved until death or for at least 5 years.

PMID- 8747952
TI  - Cerebellar mutism: report of seven cases and review of the literature.
AB  - It is well known that degenerative disease, hemorrhage, infection, and neoplastic
      disease of the cerebellum can lead to speech disorder. Mutism after posterior
      cranial fossa surgery was first reported by Rekate et al. and Yonemasu in 1985.
      We review and analyze the cases of cerebellar mutism that are reported in the
      literature that is available in English. We found 39 reported cases that included
      details regarding mutism. We review and analyze a total of 46 cases, including
      those of our seven patients. The ages of the patient ranged from 2 to 61 years
      (mean, 10.4 yr). Ninety-one percent of the patients were children. The vermis was
      the site of the mass lesions in > 90% of the cases. The pathological findings of
      the lesions were as follows: 33 medulloblastomas, 7 astrocytomas, 4 ependymomas,
      1 metastatic tumor, and 1 arteriovenous malformation. All mass lesions were
      considered to be large or very large. The latency for the development of mutism
      ranged from 0 to 6 days (mean, 1.7 d). The mutism lasted from 4 days to 4 months
      (mean, 6.8 wk). Dysarthric speech ensued after the mutism was resolved in 35 of
      46 patients. Mutism was transient in all of the cases. Cerebellar mutism is a
      transient complication of posterior fossa surgery for midline mass lesions.

PMID- 8747953
TI  - Surgical management of dumbbell and paraspinal tumors of the thoracic and lumbar
      spine.
AB  - The lateral extracavitary approach was used for single-staged tumor resection in
      12 patients with complex dumbbell or paraspinal tumors of the thoracic and lumbar
      spine. Six women and six men (age, 28-72 yr) were treated between August 1990 and
      January 1994. The tumors included schwannoma (6 patients), malignant meningioma
      (1 patient), hemangioma (1 patient), chondrosarcoma (1 patient),
      osteocartilaginous exostosis (1 patient), radiation-induced osteogenic sarcoma (1
      patient), and metastatic renal carcinoma (1 patient). Gross total resection was
      achieved in 11 patients. Radical subtotal removal was performed in the remaining
      patient, who had a malignant osteogenic sarcoma. Concomitant spinal stabilization
      with internal fixation and anterior interbody strut grafting was performed on two
      patients. No significant perioperative complications occurred. Ten patients were
      alive and clinically stable at follow-up visits ranging from 14 to 55 months. Two
      patients died from systemic tumor dissemination during the follow-up period. The
      lateral extracavitary approach is useful when extensive or difficult spinal and
      paraspinal exposure is required. The surgical aspects of these neoplasms and the
      technique of lateral extracavitary approach are described in detail.

PMID- 8747954
TI  - Intraoperative mapping of the trigeminal nerve root: technique and application in
      the surgical management of facial pain.
AB  - A method for intraoperative topographic mapping of the trigeminal nerve root
      using electrophysiological methods is described. A series of 15 patients under
      general anesthesia during microvascular decompression and selective posterior
      fossa trigeminal rhizotomy was studied. This method was used to study the
      localization of fibers of individual subdivisions of the intradural portion of
      the trigeminal nerve and as a guide for performing physiologically controlled,
      selective, microsurgical trigeminal rhizotomy.

PMID- 8747955
TI  - Revascularization and aneurysm surgery: current techniques, indications, and
      outcome.
AB  - Revascularization is an important component of treatment for complex aneurysms
      that cannot be directly clipped and instead require parent vessel occlusion. A
      consecutive series of 61 patients with 63 aneurysms requiring cerebral
      revascularization is presented. Aneurysms were located along the petrous internal
      carotid artery (ICA) (n = 5), the cavernous ICA (n = 16), the supraclinoid ICA (n
      = 12), the middle cerebral artery (n = 17), the anterior cerebral artery (n = 4),
      the vertebral artery/posterior inferior cerebellar artery (n = 5), and the
      midbasilar artery (n = 4). Aneurysms were treated by direct clipping (n = 8),
      trapping (n = 28), proximal vessel occlusion (n = 9), distal vessel occlusion (n
      = 1), excision (n = 15), and thrombotic occlusion (n = 2). Revascularization was
      performed with petrous to supraclinoid ICA bypass (n = 12), superficial temporal
      artery to middle cerebral artery bypass (n = 15), superficial temporal artery to
      middle cerebral artery bypass with saphenous graft (n = 5), superficial temporal
      artery to superior cerebellar artery bypass (n = 4) long saphenous bypass (n =
      11), in situ bypass (n = 3), and primary reanastomosis (n = 13). Fifty-seven
      patients (93%) had good outcomes, and one patient died (surgical mortality, 2%).
      This experience demonstrates that revascularization can be performed with low
      morbidity and mortality. We think that the cumulative risks of not performing
      revascularization in patients who tolerate ICA balloon occlusion exceed the
      surgical risk of revascularization. We therefore favor revascularization in
      patients with complex aneurysms treated by surgical arterial occlusion.

PMID- 8747956
TI  - Intraoperative monitoring with pulse Doppler ultrasonography in transsphenoidal
      surgery: technique application.
AB  - We describe an intraoperative use of pulse Doppler ultrasonography in
      transsphenoidal surgery to prevent mechanical vascular injury, particularly to
      the intracavernous portion of the internal carotid artery. This system is
      integrated by connection to a video processor. The use of Doppler sonography
      provided real-time measurement of arterial or venous flow velocity and source of
      flow by both real-time sonograms and sound frequencies. With the use of a
      microprobe, 1 mm in diameter, vessels located within 7 mm from the tip of the
      probe could be easily, rapidly, and noninvasively detected, without disturbing
      operative field. Furthermore, both the size and the distance of a vessel could be
      measured by turning the dial of Doppler signal gain from initially waxing to
      waning Doppler sounds, because the acoustic sounds were adjusted to the axial
      flow of each vessel in 0.1-mm increments. Our intraoperative monitoring enhanced
      operative safety with technical simplicity and reliability.

PMID- 8747957
TI  - Proliferative activity and invasiveness among pituitary adenomas and carcinomas:
      an analysis using the MIB-1 antibody.
AB  - Although histologically benign, one-third of all pituitary tumors will be
      invasive of surrounding structures. In this study, the relationship between the
      proliferative activity in pituitary adenomas and their invasiveness was
      investigated. Invasion was defined as gross, operatively or radiologically
      apparent infiltration of dura or bone. Using the recently developed MIB-1
      monoclonal antibody, which recognizes the Ki-67 cell cycle-specific nuclear
      antigen, the growth fractions of 37 noninvasive adenomas, 33 invasive adenomas,
      and 7 primary pituitary carcinomas were determined. All tumors were fully
      classified by histology, immunohistochemistry, and electron microscopy. The mean
      Ki-67 -derived growth fractions for noninvasive adenomas, invasive adenomas, and
      pituitary carcinomas were 1.37 +/- 0.15%, 4.66 +/- 0.57%, and 11.91 +/- 3.41%,
      respectively (mean +/- standard error of the mean). An analysis of variance and
      then individual pairwise comparisons confirmed significant differences in the
      mean Ki-67 labeling index between each of the three tumor groups (P < 0.01). The
      mean growth fraction of hormonally active pituitary adenomas (3.25 +/- 0.26%) was
      significantly higher than that for nonfunctioning adenomas (2.06 +/- 0.23%) (P =
      0.03). Establishing a threshold labeling index of 3% served to distinguish
      invasive from noninvasive adenomas with 97% specificity and 73% sensitivity and
      was associated with positive and negative predictive values of 96 and 80%,
      respectively. Although invasive pituitary tumors exhibited significantly higher
      growth fractions than did noninvasive tumors, there were individual exceptions,
      indicating that in a subpopulation of invasive pituitary tumors, factors other
      than proliferative activity determine invasive potential.

PMID- 8747958
TI  - Inhibitors of protein tyrosine phosphorylation reduce the proliferation of two
      human glioma cell lines.
AB  - Epidermal growth factor (EGF) and platelet-derived growth (PDGF) are suggested to
      be involved in the proliferation of human gliomas. We examined the effects of
      these growth factors on two human malignant glioma cell lines. Treatment of the
      A172 glioblastoma and the Hs683 glioma cell line with EGF and PDGF resulted in
      the tyrosine autophosphorylation, and hence activation, of the respective growth
      factor receptors. In addition, both cell lines responded to EGF and PDGF with
      increased deoxyribonucleic acid (DNA) synthesis. Because the intrinsic protein
      tyrosine kinase activity of this class of growth factor receptors is
      indispensable for their functioning, we tested the effects of specific protein
      tyrosine kinase inhibitors on growth factor-induced DNA synthesis and glioma cell
      proliferation. Genistein inhibited both EGF- and PDGF-stimulated
      autophosphorylation of the receptors and induction of DNA synthesis. However,
      genistein seemed to be cytotoxic to the cells. The tyrphostins RG 50875 and RG
      13022 dose-dependently inhibited DNA synthesis induced by EGF, PDGF, and serum.
      RG 13022 completely blocked the EGF- and PDGF-induced DNA synthesis at a
      concentration of 50 mumol/L. The tyrphostins showed no selectivity in blocking
      either EGF or PDGF signaling. With concentrations up to mumol/L, no cytotoxic
      side effects of the tyrphostins were observed. Both tyrphostins also inhibit
      serum-driven cell growth in a dose-dependent manner. These results support the
      hypothesis that activated protein tyrosine kinase receptors are involved in the
      proliferation of A172 and Hs683 glioma cells. Selective inhibitors of protein
      tyrosine kinases, therefore, might have the potential to contribute to the
      treatment of growth factor-dependent gliomas.

PMID- 8747959
TI  - Prevention of cerebral vasospasm after experimental subarachnoid hemorrhage by RO
      47-0203, a newly developed orally active endothelin receptor antagonist.
AB  - Since their discovery in 1988, endothelins have attracted scientific interest
      because of their extremely potent and long-lasting vasoconstrictive effects,
      similar to cerebral vasospasm in humans. In this study, the efficacy of the
      orally active endothelin receptor antagonist RO 47-0203 for prevention of
      cerebral vasospasm after experimental subarachnoid hemorrhage, using the two
      hemorrhage dog model, was investigated. Twenty-eight beagle dogs were used in
      this laboratory experiment. Fourteen animals each were assigned to the treatment
      and control groups. In the treatment group, each dog received two single doses of
      30 mg/kg RO 47-0203 orally per day. The diameter of the basilar artery decreased
      from 1.36 +/- 0.17 mm on Day 1 to 1.19 +/- 0.23 mm on Day 8 in the treatment
      group, whereas in the control group, the vessel diameter decreased from 1.48 +/-
      0.19 mm on Day 1 to 1.02 +/- 0.22 mm on Day 8. These results corresponded to a
      decrease of vessel diameter of 13.1% +/- 11.2% in the treatment group and a
      decrease of vessel diameter of 30.7% +/- 12.4% in the control group (P < 0.001).
      Concentrations of endothelin-1 in cerebrospinal fluid significantly increased
      with time after subarachnoid hemorrhage. These results emphasize the important
      role of endothelin in the development of cerebral vasospasm and present first
      time evidence that prevention of cerebral vasospasm can be achieved by the
      endothelin receptor antagonist RO 47-0203.

PMID- 8747960
TI  - Mapping of lactate and N-acetyl-L-aspartate predicts infarction during acute
      focal ischemia: in vivo 1H magnetic resonance spectroscopy in rats.
AB  - The time course, anatomic distribution, and extent of changes in cerebral
      lactate, N-acetyl-L-aspartate (NAA), and other metabolite levels determined by
      three-dimensional in vivo 1H magnetic resonance spectroscopy and single-voxel
      spectral analysis after middle cerebral artery occlusion in rats. Increased
      lactate was detected in the central ischemic region within 1.3 hours after the
      onset of permanent occlusion (n = 22) or 0.5 hour after the onset of 1 hour of
      temporary occlusion and then reperfusion (n = 8). Permanent occlusion resulted in
      persistent lactate elevation and a 25.4 +/- 4.1% reduction in the NAA peak after
      1.3 hours; NAA was almost completely depleted after 24 hours. Results also
      demonstrated delayed depletion of all other magnetic resonance spectroscopy
      visible 1H metabolites, including creatine, choline, and glutamate, after
      permanent occlusion. After 1 hour of temporary focal ischemia, lactate returned
      to nearly normal levels within 0.4 hour after the onset of reperfusion; at 72
      hours, a recurrent increase in lactate and a new decrease in NAA were observed,
      suggesting delayed tissue injury. Histological analysis, performed in 10 rats,
      demonstrated infarcts that corresponded in distribution to regions of NAA
      depletion at 72 hours. These findings indicate that lactate elevation is a
      sensitive early marker of ischemia; however, temporary recovery of lactate
      accumulation after reperfusion did not predict sustained metabolic recovery. In
      contrast, NAA depletion within 1.3 hours after the onset of ischemia identified
      central ischemic regions that were destined for infarction. Potential clinical
      applications include selection and monitoring of therapeutic intervention, as
      well as prediction of outcome, in patients with acute stroke.

PMID- 8747961
TI  - The effect of mannitol on experimental cerebral ischemia, revisited.
AB  - The effect of 20% mannitol on ischemic neuronal injury was examined in male
      Wistar rats (n = 80) that were randomly divided into forebrain and focal ischemia
      groups. The animals were further subdivided into control, treatment with mannitol
      before ischemia (1 g/kg of body weight, 12 min before ischemia), and treatment
      with mannitol after ischemia (0.25 g/kg of body weight, beginning 20 min after
      ischemia and then every 6 h for 48 h) groups. Physiological parameters were
      carefully monitored and maintained within normal limits. The administration of
      mannitol after ischemia was found to produce a statistically significant
      improvement in ischemic neocortical injury and selective neuronal necrosis in the
      neocortex in the forebrain and focal models, respectively. However, treatment
      with mannitol after ischemia was shown not to favorably alter histopathological
      outcome in hippocampal levels 2 through 7 in the forebrain model nor did not
      reduce infarct volume in the focal ischemia group. Treatment with mannitol before
      ischemia did not produce statistically significant reductions in neuronal injury
      in either model. These results do not support the findings of previous
      investigations, which have demonstrated that mannitol affords a significant
      degree of neuroprotection when administered either before or immediately after
      vessel occlusion in models of forebrain and focal cerebral ischemia. The
      neuroprotective effect of mannitol demonstrated in the neocortex of both
      forebrain and focally ischemic rats may support the theory that the main
      mechanisms responsible for neocortical injury in ischemia differ from those in
      the striatum hippocampus. Finally, mannitol's ability to reduce ischemic neuronal
      injury most effectively when administered after rather than before the production
      of ischemia is consistent with a possible beneficial influence on the development
      of delayed cerebral edema.

PMID- 8747962
TI  - Regional activity of ornithine decarboxylase and edema formation after traumatic
      brain injury.
AB  - This study examined ornithine decarboxylase (ODC) activity and edema formation
      bilaterally in brain cortices and hippocampi after lateral controlled cortical
      impact injury in rats. To measure the activity of ODC, the brains of injured and
      control rats were frozen in situ at 30 minutes and at 6, 24, and 72 hours after
      controlled cortical-impact injury of moderate severity. The specific gravity of
      these regions was examined in decapitated animals at corresponding time points as
      an indicator of edema formation. Thirty minutes after injury, ODC activity did
      not increase in the injury-site cortex and ipsilateral hippocampus. At 6 hours
      after injury, ODC activity had increased by nine times that of the control in the
      injury-site cortex, by five times in the adjacent cortex, and by five and one
      half times in the ipsilateral hippocampus. Twenty-four hours after injury, ODC
      activity had increased by three times that of the control in the injury-site
      cortex and two times in the ipsilateral hippocampus. Seventy-two hours after
      injury, activity had returned to control levels. ODC activity increased
      significantly in the contralateral cortex and hippocampus only at 6 and 24 hours.
      The injury-site and adjacent cortices and the ipsilateral hippocampus showed
      significant edema at 6, 24, and 72 hours but not at 30 minutes after injury.
      These findings indicate that polyamine metabolism is significantly altered in
      traumatic brain injury. The temporal association between ODC activity and edema
      formation indicates that polyamines might be a contributing factor in edema
      formation after traumatic brain injury. The delayed induction of ODC after brain
      injury suggests a potential therapeutic window for future pharmacological
      intervention to decrease posttraumatic secondary cerebral injury.

PMID- 8747963
TI  - Yale neurosurgery program.
AB  - Organized neurosurgery at Yale began in 1918 with Dr. Sam Harvey. In 1928, Dr.
      William German became the first surgeon at Yale who was dedicated to
      neurosurgery. Both of these surgeons were trained by Harvey Cushing, and upon the
      arrival of Drs. Cushing and Eisenhardt in 1934, Yale developed a strong tradition
      in surgery of the nervous system. In 1967, Dr. William Collins established a
      training program for residents that integrated laboratory research and clinical
      experience. This tradition has continued under the guidance of Dr. Dennis Spencer
      since 1987. This article provides a brief overview of the history of neurosurgery
      at Yale, its current practice, and plans for the future.

PMID- 8747964
TI  - Cerebral salt wasting syndrome: a review.
AB  - Hyponatremia is frequently seen in neurosurgical patients and is often attributed
      to inappropriate secretion of antidiuretic hormone. A number of studies in recent
      years have shown that hyponatremia in many patients with intracranial disease may
      actually be caused by cerebral salt wasting, in which a renal loss of sodium
      leads to hyponatremia and a decrease in extracellular fluid volume. The
      appropriate treatment of cerebral salt wasting fluid and salt replacement, is
      opposite from the usual treatment of hyponatremia caused by inappropriate
      secretion of antidiuretic hormone. This review summarizes the evidence in favor
      of cerebral salt wasting in patients with intracranial disease, examines the
      possible mechanisms responsible for this phenomenon, and discusses methods for
      diagnosis and treatment.

PMID- 8747965
TI  - The neurovascular relationships and the blood supply of the trochlear nerve:
      surgical anatomy of its cisternal segment.
AB  - We examined in detail the cisternal segments of 15 trochlear nerves in brain
      stems injected with India ink and fixed in formalin. The nerves were found to
      emerge as singular trunks (33.3%), singular trunks with accessory rootlets
      (13.3%), or two or three roots with (26.7%) or without accessory rootlets
      (26.7%). The nerves were in close relationship or in contact with the superior
      cerebellar artery, that is, with the main trunk of the superior cerebellar
      artery, its medial and lateral terminal stems, the accessory superior cerebellar
      artery, and the vermian, paravermian, collicular, and lateral hemispheric
      arteries as well as their small branches. Some of these vessels were connected by
      anastomoses in 86.7% of the cases. The anastomotic channels varied from 40 to 530
      microns in diameter. The cisternal segment of each trochlear nerve was usually
      supplied by a single long artery, which most often arose from the vermian artery
      (26.7%) or the collicular artery (26.7%). The feeding vessel ranged from 30 to 80
      microns in caliber. We discuss the possible clinical significance of the anatomic
      data observed in the present study.

PMID- 8747966
TI  - A phantom study to assess the accuracy of stereotactic localization, using T1
      weighted magnetic resonance imaging with the Leksell stereotactic system.
AB  - This phantom study assesses the accuracy of stereotactic localization using the
      Leksell G frame (Elekta Instruments AB, Stockholm, Sweden) with T1-weighted
      magnetic resonance imaging (Siemens 1.5 T Magnetom; Erlangen, Germany). The
      coordinates of an array of solid perspex rods were determined and compared with
      measured values in a series of transverse, coronal, and sagittal images. The
      maximum absolute errors observed (X = 2.7 mm, Y = 7.0 mm, Z = 8.0 mm) were
      discouraging. However, the more reasonable mean errors (X = 0.4 mm, Y = 0.7 mm, Z
      = 1.3 mm) reflect considerable variation in accuracy throughout the volume
      assessed and limitation of maximum errors to specific areas. We present details
      of the spatial variation and discuss possible mechanisms for improving accuracy.
      The overall results are of direct relevance only to the scanner used. These
      results are, however, an indication of the need to approach with caution
      stereotactic localization using magnetic resonance imaging and to emphasize the
      requirement for quality assurance and for a comprehensive study of the scanner's
      characteristics.

PMID- 8747967
TI  - Clinical syndromes associated with disproportionate weakness of the upper versus
      the lower extremities after cervical spinal cord injury.
AB  - Patients with cervical spinal cord injuries who present with weakness or
      paralysis of the hands and arms with relative preservation of lower extremity
      strengths are often categorized as having two clinical syndromes, cruciate
      paralysis and acute central cervical spinal cord injury. The explanation for the
      pathophysiological findings of the dissociated strength in the upper versus the
      lower extremities has relied on the assumption that there is a localized injury
      within a somatotopically organized corticospinal tract. This article summarizes
      the evidence that there is no somatotopic organization within the corticospinal
      tract in the medulla or cervical spinal cord in primates. An alternative
      hypothesis for these two syndromes is presented and is based on evidence that has
      demonstrated that the corticospinal tract in primates is critical for hand
      function but not for locomotion. Other prevailing theories are reviewed. Thus, we
      propose that a syndrome consisting of relatively greater hand and arm weakness
      compared with leg weakness can occur after an injury to the corticospinal tracts
      in the medulla or the cervical cord. The proposed mechanism, based on the
      function of the corticospinal tract, unifies a spectrum of injuries of the lower
      medulla and cervical spinal cord, which produce similar clinical syndromes
      (cruciate paralysis and acute central cervical spinal cord injury).

PMID- 8747968
TI  - Intramedullary spinal cord germinoma: case report and review of the literature.
AB  - We discuss the case of a patient with a recurring intramedullary spinal cord
      germinoma of the lower thoracic spinal cord, which was successfully excised. A
      primary intramedullary spinal cord germinoma is very rare, and only four other
      cases have been reported in the literature. All five cases are reviewed regarding
      the appearance of the germinomas, their neuroradiological features, and their
      histopathological findings. We also discuss treatment choices for germinomas of
      the spinal cord.

PMID- 8747969
TI  - Invasive mole presenting as a spinal extradural tumor: case report.
AB  - The most common sites of metastatic lesions that are caused by an invasive mole
      are lung, liver, and brain. Spinal spread is very rare. We present a 24-year-old
      patient with paraparesis that was caused by an extradural spinal invasive mole.
      Surgery, for decompression and biopsy, and subsequent chemotherapy resulted in
      complete recovery.

PMID- 8747970
TI  - Acute median nerve compression at the distal forearm caused by a thrombosed
      aneurysm of an epineural vessel: case report.
AB  - The case of a patient with a 2-day history of symptoms suggesting acute carpal
      tunnel syndrome is presented. However, an urgent electroneurographic examination
      revealed median nerve compression at the forearm and magnetic resonance imaging
      confirmed compression by a mass proximal to the carpal tunnel. Surgical
      exploration showed a recently thrombosed aneurysm of an epineural vessel.
      Histological and, later, general and angiological investigations could not reveal
      the underlying cause of this aneurysm. Preoperative electrodiagnostic examination
      is recommended in acute peripheral nerve compression to prevent decompression at
      an incorrect site. If atypical nerve compression is suspected, magnetic resonance
      imaging may be indicated to detect localized nerve compression and its underlying
      cause.

PMID- 8747971
TI  - Subarachnoid hemorrhage secondary to a ruptured inflammatory aneurysm: a possible
      manifestation of neurocysticercosis: case report.
AB  - We report a case of a 32-year-old man who presented with subarachnoid hemorrhage.
      As revealed by lumbar puncture, the cerebrospinal fluid had low glucose, high
      protein levels, and pleocytosis with 5% of eosinophils. Cultures were negative.
      Enzyme-linked immunosorbent assay and complement fixation reactions for
      cysticercosis in cerebrospinal fluid were positive. An angiogram revealed an
      aneurysm of the right anteroinferior cerebellar artery. At surgery, the aneurysm
      was found to be surrounded by thickened leptomeninges, which histologically
      presented dense inflammation and remains of Cysticercus. The aneurysm could not
      be clipped, and it was wrapped. Postoperatively, the patient had dizziness and
      right ear tinnitus. He received prednisone therapy on alternate days and
      subsequently received albendazole for subarachnoid cysticerci. At the 4-year
      follow-up, the patient was asymptomatic and had normal cerebrospinal fluid.
      Although we cannot rule out a congenital aneurysm, its location inside an area of
      severe arachnoiditis around a cysticercus suggests an inflammatory origin. This
      type of vascular lesion not reported before should be suspected in patients with
      chronic cysticercotic meningitis.

PMID- 8747972
TI  - Vertical fracture of the odontoid process: case report.
AB  - Fifteen percent of cervical spine fractures involve the odontoid process. Most
      odontoid fractures can be classified as Types I through III according to the
      scheme developed by Anderson and D'Alonzo. We report a case of a vertically
      oriented fracture through the odontoid process that does not fit into any of
      these categories. Only two such cases have been described in the literature. Our
      patient is an 18-year-old man who sustained an axial loading injury to his
      cervical spine. Plain lateral cervical tomography and computed tomography were
      performed to characterize the fracture and to evaluate the instability. The
      patient was placed in a rigid orthosis for 12 weeks, and at 6-month follow-up, he
      had full range of motion and showed no evidence of abnormal movement, as revealed
      by flexion-extension studies. This case demonstrates the shortcomings of the
      current classification system for odontoid fractures and value of plain
      tomography and computed tomography in evaluating odontoid fractures.

PMID- 8747973
TI  - Intrathecal octreotide for relief of intractable nonmalignant pain: 5-year
      experience with two cases.
AB  - Somatostatin is distributed in the substantia gelatinosa in the dorsal horn of
      the spinal cord, and its application has been found to produce an inhibitory
      effect on nociceptive neurons. Although intraspinal administration of
      somatostatin-14 produces pain relief in patients with cancer and in postoperative
      patients, its short half-life limits its clinical usefulness. Octreotide, a
      synthetic analog of somatostatin, is more stable and not been associated with
      neurodegenerative changes when administered intrathecally in dogs. Intrathecal
      octreotide provides analgesia without adverse drug effects when administered
      chronically for cancer pain; however, treatment periods have been limited. This
      article describes the 5-year clinical course of two patients receiving
      intrathecal octreotide for severe, intractable nonmalignant pain. Included in
      this description are the results of blinded, randomized "N of 1" trials conducted
      in each of these patients.

PMID- 8747974
TI  - Reconstruction of the spinal accessory nerve with an anastomosis to the dorsal C3
      branch: technical note.
AB  - Most lesions of the spinal accessory nerve are of traumatic origin. If the
      proximal part is sectioned next to its exit from the cranial base, the
      reconstruction might be difficult. In such a case, one option is intracranial
      identification of the spinal accessory nerve and transdural interposition of a
      graft to its distal stump. Cerebrospinal fluid leaks or infections, caudal nerve
      palsies, or even spinal neurological deficits are possible complications. From
      more than 70 patients who underwent selective peripheral denervations for the
      treatment of spasmodic torticollis in our department, we have learned that the
      dorsal C1-C6 branches can be sectioned without any functional impairment. The
      dorsal C2 and C3 branches have diameters comparable to that of the spinal
      accessory nerve. They contain between 600 and 700 myelinated fibers per square
      millimeter. Therefore, they seem to be ideal proximal donors for the
      reconstruction of a severed motor nerve. They may be used in patients with
      peripheral nerve injuries in the craniocervical region, if other possibilities
      are not suitable.

PMID- 8747975
TI  - C1-C2 fusion in children with atlantoaxial instability and spinal cord
      compression: technical note.
AB  - Children with atlantoaxial instability and subluxation that will not reduce with
      extension of the cervical spine often present with clinical and/or radiographic
      evidence of spinal cord compression at the C1-C2 level. If the patient requires a
      laminectomy at the C1 level, occipital fusion is necessitated with associated
      reduction in mobility and high incidence of nonunion, as compared with a C1-C2
      fusion. Also, passing wires under the intact lamina at C1 can further compromise
      an already compressed cervical cord. To address the problems associated with
      either of the above options, we used a C1-C2 fusion with removal of the mid 2 cm
      of the lamina of C1. Another option is the application of a transarticular screw
      fixation of C1-C2, which does not require the posterior element of C1. The
      current study was performed before the introduction of this type of fixation.
      Over a 10-year period, we have used the described technique to treat 13 patients.
      After decompression and fusion at the C1 and C2 levels as described, all patients
      had resolution of their preoperative neurological symptoms and all have achieved
      a stable fusion. Partial removal of the lamina at C1 and then C1-C2 fusion are
      safe and effective procedures to treat children with atlantoaxial instability and
      spinal cord compression.

PMID- 8747976
TI  - Pressure-controlled drainage of cerebrospinal fluid: clinical experience with a
      new type of ventricular catheter (Ventcontrol MTC)and an integrated Piezo
      resistive sensor at its tip: technical note.
AB  - We described a new ventricular catheter that is the combination of a "classic"
      ventricular catheter with a piezo-resistive transducer at its tip. The device
      allows parallel recordings of intraventricular fluid pressure via a chip and a
      fluid-filled external transducer, drainage of cerebrospinal fluid from the
      ventricle or injection of fluid into the ventricle with simultaneous monitoring
      of intracranial pressure, and recording of brain tissue pressure in cases of
      misplacement or dislocation of the ventricular catheter or in cases of
      progressively narrowing ventricles caused by brain edema. Clinical tests in
      various situations at different pressure ranges (total recording time, 1356 h in
      13 patients) gave excellent correlations of both pressures. Application of the
      device is especially indicated in clinical situations in which pressure
      controlled drainage is desirable, occlusion of ventricular bolts is likely, or
      pressure-volume tests are needed.

PMID- 8747977
TI  - Laboratory testing of three intracranial pressure microtransducers: technical
      report.
AB  - Three comparatively priced intracranial pressure (ICP) microtransducers are now
      available, each characterized by the manufacturer as having very low zero drift
      over long periods, an excellent frequency response, and a low measurement error.
      The three microtransducers, coded Transducer A (Camino OLM ICP monitor; Camino
      Laboratories, San Diego, CA), Transducer B (Codman Microsensor ICP Transducer;
      Codman & Shurtlef Inc., Randolph, MA), and Transducer C (ICP Monitoring Catheter
      Kit OPX-SD [4F]; InnerSpace Medical, Irvine, CA), were examined in a pressure
      flow test rig designed for assessment of hydrocephalus shunts. All three
      microtransducers compiled with the manufacturers' specifications and gave high
      quality readings under test conditions. However, some differences were noted;
      Transducer C had the lowest 24-hour zero drift (drifts in all transducers were <
      0.8 mm Hg). The temperature drift was very low in Transducer B and C, but
      Transducer A had a significantly higher drift (0.27 mm Hg/degrees C). Transducer
      A had a static error < 0.3 mm Hg, Transducer B < 2 mm Hg, and Transducer C < 8 mm
      Hg. Frequency detection in Transducers A and B were very good (bandwidth, > 30
      Hz), whereas Transducer C had a limited bandwidth of 20 Hz. Transducer B scored
      the best overall, but all three scored satisfactorily during bench testing.

PMID- 8747978
TI  - Pallidotomy in Parkinson's disease.

PMID- 8747979
TI  - Early discharge after carotid endarterectomy.

PMID- 8747980
TI  - Treatment of head injury in mice, using a fructose 1,6-diphosphate and dimethyl
      sulfoxide combination.

PMID- 8747981
TI  - Propylene glycol toxicity following continuous etomidate infusion for the control
      of refractory cerebral edema.

PMID- 8747982
TI  - Blood stem cell transplantation: from preclinical to clinical models.
AB  - This introductory statement to the International Symposium "Ten Years of Blood
      Stem Cell Transplantation in Heidelberg" provides the opportunity to review the
      experimental work that was necessary to set the stage for the first successful
      clinical studies to use blood-derived stem cells to treat hemopoietic and other
      malignancies. The Ulm University research group used the preclinical canine model
      to systematically and extensively explore the possibilities and limitations of
      the therapeutic use of blood-derived hemopoietic stem and progenitor cells. It
      became clear that blood stem cells are physiological elements of the circulating
      blood, that their concentration can be drastically increased by chemical and
      biological means, that they do not lose their function during appropriate
      cryopreservation, and that they can be "purified" and used successfully to
      restore hemopoiesis after myeloablative conditioning both in the autologous and
      allogeneic situation. If compared to fetal liver-derived stem cells, there is
      excellent experimental evidence that fetal liver-derived stem cells may have even
      more potential in their ability to restore hemopoiesis, and it is evident that
      much more experimental work is needed.

PMID- 8747983
TI  - Assessment and characterization of hemopoietic stem cells.
AB  - The adequate production of blood cells is sustained by pluripotent hemopoietic
      progenitors whose behavior is influenced by a permissive hemopoietic
      microenvironment. Hemopoietic progenitors have in common the expression of CD34
      surface molecules, but are heterogeneous with respect to other properties. It is
      commonly accepted that primitive progenitors, considered to be candidates for
      marrow repopulating cells, are HLA-DR-, without expressing lineage-specific
      determinants. They are usually quiescent with respect to their cell cycle status.
      In addition to CD34, they may display adhesion molecules on their surface and
      express receptors for ligands such as c-kit, FLT2/FLK3 and various other
      cytokines. Some of these are expressed constitutively, while others emerge as the
      cells progress through their regular maturation program. This process appears to
      include a gradual reduction of their proliferative capabilities as demonstrated
      by a progressive loss of the length of their telomeric structures.

PMID- 8747984
TI  - Peripheral blood stem cell transplantation in acute myeloid leukemia: the
      experience of the Bordeaux Group.
AB  - Since our initial report of successful peripheral blood stem cell transplantation
      (PBSCT) in a patient with acute myeloid leukemia (AML), we have performed more
      than 300 PBSCTs; 49 of them were done for AML patients. PBSC mobilization (and
      collection) was influenced by the number of previous courses of chemotherapy and
      significantly increased when G-CSF was combined with chemotherapy for
      mobilization. Hematopoietic recovery (HR) was complete in every patient. The HR
      rate was influenced by the number of cells transplanted. Platelet recovery was
      significantly quicker for patients given G-CSF for mobilization. The outcome of
      patients transplanted in first or second remission was similar to that usually
      observed after bone marrow transplantation.

PMID- 8747985
TI  - The Nebraska experience.
AB  - Autologous peripheral stem cell transplantation was initiated at the University
      of Nebraska Medical Center to provide hematopoietic rescue for patients who were
      candidates for high-dose therapy but had marrows that were unfit for
      autografting. From 1984 until 1991, the cells were collected during steady state
      without mobilization. These cells restored hematopoietic function at a rate
      similar to that of autologous marrow in patients not treated with total body
      irradiation. Patients who received total body irradiation experienced slower
      hematopoietic recovery. When growth factors became generally available in the
      United States in 1991, mobilization with cytokines became standard at Nebraska.
      In recent years, the function of cells other than hematopoietic progenitors
      contained in a peripheral stem cell apheresis product has been studied. Detection
      of tumor cells using cell culture, immunocytochemical and polymerase chain
      reaction techniques has revealed that such collections are less likely to
      contain, or contain fewer, tumor cells than autologous bone marrow harvests. More
      antitumor cytotoxic activity was found in cells in peripheral stem cell
      collections than in marrow cell collections. The immunocompetent lymphocyte
      population is larger in peripheral stem cell collection than in marrow harvests,
      and immunologic recovery after peripheral stem cell transplant has differed
      compared to recovery following bone marrow transplantation. The future of
      peripheral stem cell transplantation is likely to include engineering of the
      graft products specific for the patient and disease being treated. Determining
      the function of accessory cells in a peripheral stem cell collection will be
      important to provide the best engineered product for the patient.

PMID- 8747986
TI  - High-dose therapy with peripheral blood progenitor cell support in patients with
      non-Hodgkin's lymphoma.
AB  - Between September 1991 and April 1995, high-dose therapy with peripheral blood
      progenitor cell (PBPC) support was administered to 105 patients with non
      Hodgkin's lymphoma (NHL). Thirty-three patients had high-grade NHL, while 72
      patients had different forms of low- or intermediate-grade NHL. Except for three
      patients who received G-CSF during steady-state hematopoiesis, PBPCs were
      collected following cytokine-supported cytotoxic chemotherapy. This included G
      CSF or the sequential administration of interleukin 3 (IL-3) and GM-CSF.
      Assessing bone marrow (BM) samples before the start of chemotherapy and
      leukapheresis (LP) products collected during cytokine-enhanced marrow recovery, a
      2.3-fold greater mean concentration of CD34- cells was found in peripheral blood
      (p < 0.005). The blood-derived progenitor cells were enriched with a particular
      subset of more primitive progenitors, as the mean proportion of CD34+/Thy-1+
      cells in LP products was three-fold greater in comparison to premobilization BM
      samples, respectively (p < 0.001). In contrast, the mean proportion of
      CD34+/CD19+ and CD19+ cells in LP products was 8.8- and 80-fold smaller compared
      to BM samples, respectively (p < 0.001). Following high-dose conditioning therapy
      including TBI in 74 patients, reinfusion of PBPC resulted in rapid and sustained
      engraftment in the majority of patients, while in seven patients an unsubstituted
      platelet count of greater than 20 x 10(9)/l was reached between 31 and 51 days.
      Five patients died of treatment-related complications between 13 and 188 days
      following transplantation. The probability of long-term disease-free survival at
      30 months in patients autografted while they were in first remission was 70% in
      high-grade and 83% in low-grade NHL, respectively. The data may provide the
      rationale for the use of PBPC-supported high-dose regimens as first-line
      treatment for patients at high risk of treatment failure.

PMID- 8747987
TI  - Sequential high-dose treatment with peripheral blood progenitor cell
      transplantation in patients with multiple myeloma.
AB  - In June 1992, we started a dose-escalated cytotoxic therapy with peripheral blood
      progenitor cell (PBPC) transplantation in patients with chemosensitive multiple
      myeloma (MM). At the time of best response to conventional treatment, 70 patients
      received high-dose cyclophosphamide (HD-CY) or, in case of pre-existing heart
      disease, dose-escalated ifosfamide/mitoxantrone followed by filgrastim (R-metHuG
      CSF, 300 micrograms/day). PBPC collection was commenced when CD34+ cells were
      detectable using direct immunofluorescence analysis. Fifty-four out of 70
      patients were successfully harvested (> or = 2.5 x 10(6) CD34+ cells/kg body
      weight [BW]) after the first cycle of HD chemotherapy. Conditioning therapy
      consisted of 140 mg/m2 melphalan plus TBI (14.4 Gy hyper-fractionated) or 200
      mg/m2 melphalan in patients not eligible for TBI because of previous
      radiotherapy. To date, 56 patients have been transplanted. Autografts contained a
      median of 3.4 x 10(6) CD34+ cells/kg BW. Following reinfusion of PBPC, rapid
      engraftment was achieved in 54 out of 56 patients with a median of 14 days (range
      9-23) to reach 0.5 x 10(9)/l neutrophils and 10 days (range 5-22) for an
      unsubstituted platelet count of > 20 x 10(9)/l. One patient died of
      transplantation-related complications. Sequential HD treatment improved the
      remission status (European Bone Marrow Transplantation criteria) in 19 out of 46
      patients (9 patients too early). Of note, in 11 patients the immunofixation
      became negative and a polyclonal immunoglobulin reconstitution was achieved. Our
      protocol provides an effective treatment strategy for patients with advanced MM
      combined with low treatment-related toxicity.

PMID- 8747988
TI  - Detection of minimal residual disease by polymerase chain reaction in B cell
      malignancies.
AB  - It was the aim of this study to examine the prognostic value of the detection of
      minimal residual disease (MRD), with the help of the polymerase chain reaction
      (PCR), in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM)
      who underwent sequential high-dose therapy with peripheral blood progenitor cell
      (PBPC) support, and in patients with acute myeloid leukemia (AML) of the subclass
      M4Eo who underwent high-dose consolidation therapy. Basis for the application of
      a PCR assay in these disease entities are the following specific gene
      rearrangements: the t(14;18) translocation in a high percentage of NHL, the
      clonal rearrangement of the Ig heavy chain locus resulting in a unique
      complementary determining region 3 (CDR3) for MM region and the inversion 16
      characteristic for the M4Eo subclass of AML. Before the G-CSF-supported cytotoxic
      chemotherapy was given, 65% of the 52 patients with low- and intermediate-grade
      NHL enrolled into the study had PCR+ bone marrow (BM) and/or peripheral blood
      (PB) samples. The majority of patients (29 of 52) were autografted with a PCR+
      transplant. The proportion of harvests containing t(14;18)+ cells was two-fold
      less in patients mobilized in first remission than in those with a history of
      previous treatment failure. This was also reflected when examining the B cell
      contents of the harvests measured as CD19+ cells with a 3.3-fold smaller
      proportion of CD19+ cells in leukapheresis (LP) products of patients mobilized in
      first remission. Patients who received a PCR- transplant are in remission and
      remained PCR- in BM and PB samples post-transplantation. Conversion to PCR
      negativity in BM and PB samples post-transplantation was observed in 11 of 19
      patients who were also in remission. In contrast, 6 of 29 patients who were
      autografted with PCR+ products relapsed, while 4 of them presented with PCR-
      samples on several occasions post-transplantation. In patients with MM, the
      assessment of MRD in PBPC harvests was based on the CDR3 regions of the Ig heavy
      chain locus as a marker for clonality. The great majority of LP products (17 out
      of 19) contained tumor cells. To prove positive enrichment procedures for the
      elimination of tumor cells, CD34+ and CD19+ cell fractions obtained from LP
      samples in an experimental setting via preparative flow cytometry were analyzed
      for MRD resulting in PCR-negativity for all CD34+ fractions. The results of the
      four patients with AML M4Eo and inversion 16 are preliminary, with a tendency of
      persistence of PCR-positivity after finishing the high-dose consolidation
      therapy. In one case, recurrence of disease was accompanied by an increase of the
      signal strength in the PCR assay. Longer follow-up periods are necessary to
      determine the prognostic value of these PCR findings in the different disease
      entities.

PMID- 8747989
TI  - Purging of peripheral blood stem cell grafts.
AB  - The shortage of HLA-matched sibling donors for bone marrow transplant patients
      has stimulated interest in the use of alternative donors. As a result, there has
      been a dramatic increase in the use of autologous marrow transplantation, which
      avoids the complications of graft-versus-host disease, but may deprive the
      patient of a potentially beneficial graft-versus-disease response and runs the
      risk of returning occult tumor cells with the graft. There is increasing evidence
      that these cells may be associated with disease relapse post-transplant, and many
      methods have been developed for their removal ex vivo. Combinations of negative
      and positive selection may achieve elimination of tumor cells to the limits of
      detection of the most sensitive assays currently available. The marked trend
      toward the use of autologous grafts derived from blood rather than marrow has
      raised the question as to whether peripheral blood stem cell (PBSC) preparations
      should be purged of tumor. Data indicate that these grafts generally contain a
      lower tumor burden, although the stem cell mobilization procedure may recruit
      tumor cells into the peripheral circulation. Enrichment of CD34+ cells from
      apheresis products appears, at present, to be less efficient than from marrow and
      provides at best about a 2-3 log depletion of tumor. This has prompted proposals
      to follow positive selection by a small-scale purging procedure. Technical
      issues, such as preprocessing and pooling of collections prior to purging, remain
      to be addressed. Ultimately, the development of successful purging procedures for
      PBSC grafts will simply reemphasize the necessity of improving the efficacy of
      high-dose therapy.

PMID- 8747990
TI  - Transplantation of allogeneic peripheral blood stem cells.
AB  - Recombinant G-CSF has been given to over 150 normal donors for the collection of
      allogeneic or syngeneic peripheral blood stem cells (PBSCs). G-CSF was found to
      be well-tolerated with mild-moderate bone pain, edema and mild thrombocytopenia
      being the observed side effects. To date, approximately 100 unmodified primary
      PBSC transplants from HLA-identical related donors have been performed with
      engraftment that is, in general, considerably more rapid than marrow. Acute graft
      versus-host-disease (GVHD) grades II-IV occurred in 44% of patients and grades
      III-IV in 16%. From a small number of evaluable patients surviving for more than
      100 days, it appears the incidence of chronic GVHD is approximately 50%. Despite
      the infusion of one to two logs more T cells, these results are not remarkably
      different than would be expected with marrow transplantation. Further studies are
      needed to define the role of allogeneic PBSCs for transplantation, to refine PBSC
      mobilization and collection techniques, and to evaluate the long-term effects of
      cytokines in normal donors.

PMID- 8747991
TI  - Collection of cord blood stem cells for transplantation in thalassemic patients.
AB  - Thalassemia is widely distributed throughout the world and is one of the major
      public health problems. The use of bone marrow transplantation, the only curative
      therapy for thalassemia, is limited because less than 30% of the patients have
      unaffected and HLA-identical siblings as donors. Cord blood stem cells, an
      alternative source of stem cells for transplantation, have been successfully
      transplanted into patients with several diseases after myeloablative therapy.
      Twenty cord blood samples from unaffected neonates whose siblings had severe
      thalassemia were collected. The median volume was 80 ml. The median number of
      cells and colony forming units-granulocyte-macrophage in cord blood was 9.2 x
      10(8) and 3.4 x 10(5), respectively. Four of 20 cord blood samples had HLA
      matched to the affected siblings. One patient underwent cord blood
      transplantation with success; one patient is waiting for transplantation.

PMID- 8747992
TI  - Diagnosis and monitoring of chromosome aberrations in hematological malignancies
      by fluorescence in situ hybridization.
AB  - Besides its application in biological research, fluorescence in situ
      hybridization (FISH) is increasingly used for the cytogenetic analysis of human
      malignancies. Compared to conventional cytogenetic analysis, FISH allows
      delineation of specific numerical and structural chromosome aberrations in
      interphase cells (interphase cytogenetics). We have developed sets of genomic DNA
      probes for the identification of chromosome aberrations associated with chronic
      lymphocytic leukemia (CLL), chronic myeloid leukemias (CML), and acute myeloid
      leukemia (AML). In CLL, interphase cytogenetics will greatly contribute to the
      evaluation of the true incidence of specific chromosome aberrations and will
      provide the basis for more accurate correlations with the clinical outcome. The
      Philadelphia chromosome can be detected by FISH with high specificity and
      sensitivity in both CML and acute lymphoblastic leukemia. In CML, it can be used
      to better assess the cytogenetic remission status following therapy with
      interferon-alpha. Finally, in AML interphase cytogenetics provides a rapid and
      reliable technique for the identification of chromosome aberrations which are one
      of the most important prognostic factors in this disease. With the design of
      complex DNA probe sets and the development of digital microscopy and automated
      image analysis, it will be possible to use such disease-specific probe sets for
      monitoring residual disease following chemotherapy.

PMID- 8747993
TI  - Identification of genetic imbalances in malignant lymphoma using comparative
      genomic hybridization.
AB  - In comparison to leukemias, the clinical relevance of chromosomal aberrations in
      non-Hodgkin's lymphoma (NHL) is not as well understood. This is primarily due to
      limitations of chromosomal banding techniques which have been the central methods
      for cytogenetic analysis. These techniques depend on the availability of fresh
      tumor tissue and the examination of metaphase cells which may not be
      representative for the major cell clone in vivo. In contrast, the new technique
      of comparative genomic hybridization (CGH) allows researchers to obtain a
      comprehensive view of chromosomal gains and losses by analyzing tumor DNA, which
      can be prepared from archival tissue samples. Results of CGH studies in three
      different types of lymphoproliferative disorders are outlined in this paper
      demonstrating that: (1) in chronic B cell leukemias, chromosomal aberrations are
      missed by banding analysis in a high proportion of cases, (2) CGH on paraffin
      embedded tissue samples can be used for cytogenetic analysis within clinical
      multicenter trials and (3) DNA amplifications are more frequent in NHL than
      previously assumed. Thus, it can be expected that CGH will contribute both to the
      understanding of pathogenetic mechanisms and the identification of clinically
      relevant chromosome aberrations in NHL.

PMID- 8747994
TI  - Antisense strategies in the treatment of hematological malignancies.
AB  - Antisense nucleic acids and ribozymes recognize their target in a highly sequence
      specific manner and are thought to be useful inhibitors of aberrant gene
      expression and pathogenic viral functions. Ribozymes combine the properties of
      antisense RNA and the ability to cleave the target RNA in an almost irreversible
      manner. Hematopoietic diseases such as infection of CD4+ human cells with the
      human immunodeficiency virus type 1 (HIV-1) or those forms of leukemia that occur
      as a result of chromosomal aberrations have challenged and strongly enhanced
      antisense research. Meanwhile, a number of clinical studies is conducted that
      involve the use of antisense nucleic acids and ribozymes. The aim of this review
      is to give a brief summary on the current state and the prospects of antisense
      nucleic acids and ribozymes, with particular view on antisense-mediated
      inhibition of HIV-1 replication and the expression of the ber-abl fusion gene
      that is linked with chronic myelogenous leukemia.

PMID- 8747995
TI  - Retroviral transfer of the multidrug resistance-1 gene into lineage-committed and
      primitive hemopoietic cells.
AB  - Transfer of the multidrug resistance-1 (MDR1) gene to hemopoietic cells for
      myeloprotection against cytostatic agents is a new and rapidly developing field
      in "cancer gene therapy." Before clinical application, safety and efficacy
      criteria need to be met. The retroviral producer cell lines and the retroviral
      supernatant need to be tested for replication-competent retrovirus and
      contamination with adventitious agents. The cell source needs to contain
      sufficient hemopoietic cells with repopulating ability. We used CD34(+)-selected
      mobilized peripheral blood progenitor cells (PBPC) for MDR1 transductions in
      order to obtain a favorable vector to target cell ratio. An analysis of 249
      patients who had undergone PBPC harvesting revealed that primarily solid tumor
      and non-Hodgkin's lymphoma patients are eligible for CD34+ selection. They can be
      expected to retain sufficient CD34+ cells for rapid and sustained engraftment
      after myeloablative therapy if the CD34+ cell loss (approximately 50%) during the
      procedure is taken into account. Clinical MDR1 gene therapy protocols focus on
      these two patient groups. Next we characterized MDR1 gene transfer into lineage
      committed and primitive hemopoietic cells. Provirus-specific polymerase chain
      reactions showed a high efficiency gene transfer into colony-forming-units
      granulocyte-macrophage and long-term culture cells. The level of the conferred P
      glycoprotein expression was estimated by fluorescence-activated cell sorting
      analysis to be up to 3 log above mock-transduced controls. The cobblestone area
      forming cell assay, which is a stroma-dependent long-term culture assay measuring
      frequencies of stem cell subsets in a limiting-dilution set-up, allowed
      demonstration of sustained expression of the MDR1 gene in the progeny of
      primitive hemopoietic cells. This is a favorable basis for a clinical MDR1 gene
      therapy trial.

PMID- 8747996
TI  - Stem cells as vehicles for gene therapy: novel strategy for HIV infection.
AB  - Restoration of bone marrow and immune function by means of allogeneic bone marrow
      transplantation has been attempted in AIDS patients but has not been successful
      as the donor-derived cells, or their progeny, inevitably became infected. A
      hairpin ribozyme that specifically cleaves HIV-1 RNA has been developed by F.
      Wong-Staal et al. and has been demonstrated to confer resistance against HIV-1
      infection. Allogeneic transplantation of CD34+ cells or their pluripotent
      subsets, transduced by vectors bearing this ribozyme gene, can protect the stem
      cells and their progeny from HIV-1 infection and eventually restores immune
      function. We have provided evidence that long-term repopulating stem cells can be
      mobilized into peripheral blood by growth factors. The combination of G-CSF and
      GM-CSF seems to yield a high frequency of pluripotent stem cells with a CD34+
      subset profile that is similar to placental and umbilical cord blood (PUCB). We
      have then demonstrated a highly efficient transduction of CD34+ cells from PUCB
      and mobilized leukapheresis products by retroviral vectors bearing the ribozyme
      gene. Expression of the ribozyme gene, as shown by reverse transcriptase
      polymerase chain reaction, was of similar magnitude (70%-90% of cells that grow
      into colonies). Challenge of the progeny macrophages from such transduced CD34+
      cells with monocyte-trophic strains of HIV-1 showed that they were resistant to
      infection. Thus allogeneic transplantation of CD34+ cells or their pluripotent
      subsets, transduced with ribozyme gene, can be a promising strategy for the
      treatment of HIV infection.

PMID- 8747997
TI  - Blood stem cell transplantation and gene therapy of cancer.
AB  - Based on the concept of circulating hematopoietic stem cells with indefinite self
      renewal capacity that gives rise to all three cell lineages, peripheral blood
      progenitor cells (PBPCs) have widely replaced the use of bone marrow (BM)
      progenitors for autologous transplantation purposes in patients with malignant
      hematological disorders and selected solid tumors. Ex vivo purification of normal
      CD34+ cell subsets contained in the patient's apheresis product possibly
      eliminates clonogenic tumor cells, but also serves as a target cell population
      for gene transduction. Genetic tagging of PBPC autografts has proven that: 1)
      NEOR gene expression is sustained for more than 18 months and 2) clonogenic tumor
      cells contaminating the autograft contribute to relapse. A second generation of
      gene transduction studies includes new treatment strategies such as the induction
      of chemoprotection (multidrug resistance gene-1), chemotherapy sensitization
      (p53), cancer vaccination and genetic chemosensitization. Most recently
      allogeneic PBPC transplantation has successfully been introduced with the
      intention of improving the graft-versus-leukemia effect without inducing a higher
      incidence or more severe graft-versus-host disease (GVHD) than what is expected
      after BM transplantation. Introducing the herpes virus thymidine kinase cDNA into
      activated donor T cells makes them susceptible to gangciclovir, thus allowing the
      in vivo inactivation of GVHD-inducing T cells. With the close interaction of
      molecular genetics and clinical oncology/hematology, genetic engineering of stem
      cell grafts will lead into a new stage of stem cell transplantation technology.

PMID- 8747998
TI  - Hematopoietic rescue with peripheral blood stem cells: promising strategies in
      cancer therapy.

PMID- 8747999
TI  - Peripheral blood stem cells: a historical perspective.
AB  - Peripheral blood stem cells (PBSC) are rapidly becoming the primary rescue
      modality for autologous transplantation and are now actively being investigated
      in the allogeneic transplant setting. Many investigators and clinical researchers
      believe that PBSC are likely to replace bone marrow stem cells entirely, for use
      in clinical transplantation in the not too distant future (1). In order to better
      understand the rapidly changing developments in this field, it would be helpful
      to understand the historical development of this technology. The purpose of this
      article is to build for the reader a strong historical foundation with the intent
      to integrate the history of peripheral blood stem cells with their subsequent
      isolation, mobilization, collection, and clinical applications.

PMID- 8748000
TI  - Hematopoietic "stem cell" transplantation: are there any clouds on an expanding
      horizon?
AB  - Clinicians contemplating stem cell transplantation for the treatment of their
      patients are faced with an increasing number and complexity of options for the
      source of the stem cells and their manipulation prior to transplant. Many of
      these strategies focus on the traditional concept of the "hematopoietic stem
      cell" as a unitary and independent source of reconstitution. Evolving animal
      studies suggest that the stem cell concept is incompletely defined and that the
      stem cell compartment retains significant heterogeneity of function. These
      findings should be combined with the increasingly heterogeneous goals of stem
      cell transplantation to induce caution in proceeding forward with new
      technologies.

PMID- 8748001
TI  - Methods of stem cell mobilization.
AB  - The rapid rescue of hematopoiesis following transplantation of peripheral blood
      stem cells (PBSC) has facilitated expanded application of high-dose chemotherapy
      regimens for several malignancies. A variety of regimens have been described to
      enhance the circulation of PBSC, including the use of hematopoietic growth
      factors, either alone or following myelosuppressive chemotherapy. Such
      improvements of PBSC mobilization can increase the number of hematopoietic
      progenitors for transplantation and reduce the number of leukapheresis procedures
      required. We review several approaches to the collection of PBSC, including our
      experience with the use of cytokines in addition to chemotherapy. In addition, we
      discuss the investigation of novel cytokine combinations and in vitro expansion
      techniques, which may lead to further improvements in both the efficiency of PBSC
      collection and hematopoietic recovery following transplantation.

PMID- 8748002
TI  - Stem cell purging ex vivo.
AB  - Over the last several years there has been significant progress in developing
      several techniques designed to detect contaminating tumor cells in bone marrow
      (BM) and peripheral blood progenitor cells (PBPC). These techniques include
      immunohistochemistry, in situ hybridization (ISH), flow cytometry, clonogenic
      tumor assays, and polymerase chain reaction (PCR) based assays. These assays have
      detection capabilities ranging from 1 tumor cell in 100 normal cells (ISH) to 1
      tumor cell in a million tumor cells (RT-PCR). These techniques have confirmed
      that BM and PBPC are frequently contaminated with tumor cells, with most studies
      suggesting higher tumor contamination in the BM as compared to the PBPC.
      Comparison of immunocytochemistry with the clonogenic assay has demonstrated good
      but not perfect correlation of these two techniques. Gene marking studies have
      confirmed that these tumor cells are viable and capable of contributing to
      disease relapse. Many of the assays are at least semiquantitative and are
      effective at monitoring for persistent residual tumor cell contamination after ex
      vivo processing of autografts including purging strategies and/or positive
      selection techniques. Preliminary data are conflicting, although some data
      suggest that patients receiving autografts with residual tumor cell contamination
      do worse than patients receiving autografts free of detectable tumor cells. Many
      purging techniques are capable of reducing tumor contamination by 3 to 5 logs;
      positive selection techniques are probably slightly less effective, reducing
      tumor contamination by 3 to 4 logs. The clinical benefit of purging remains to be
      demonstrated in randomized clinical trials.

PMID- 8748003
TI  - Stem cell cryopreservation.
AB  - The recent widespread use of protocols, including high dose chemotherapy with
      peripheral blood progenitor cell rescue, has resulted in increased demand for
      cryobiological services to freeze and thaw the collected progenitors. This has
      led to reexamination of many cryobiological practices and proposal of alternative
      methodologies. This review examines the scientific bases of cryobiological
      practices, how cryoprotectants work and alternative methods of freezing and
      thawing. Finally, while blood banks have come under tremendous regulatory
      pressure from federal agencies, hematopoietic stem cell processing has been
      relatively unburdened by such regulation to date. Recent meetings between the FDA
      and interested organizations make it clear that this largesse is coming to an
      end. Hence many organizations are promulgating standards that apply to marrow and
      peripheral stem cell processing.

PMID- 8748004
TI  - Stem cell transplantation with chemoradiotherapy myeloablation and interleukin-2.
AB  - Interleukin 2 (IL-2) stimulates the proliferation of T-cells both in vitro and in
      vivo. When murine or human peripheral blood (PB) or bone marrow (BM) mononuclear
      cells are incubated with IL-2 in vitro for 24 hours, cytotoxic T-cells are
      generated. If these activated cells are infused into mice, the enhanced
      cytotoxicity continues if low dose IL-2 is administered. This combination of
      administering activated cells with the subsequent low dose IL-2 infusion results
      in enhanced tumor cell destruction and improved survival rates in mice with acute
      myeloid leukemia. The encouraging results of these laboratory experiments
      prompted the initiation of phase I clinical trials in patients with
      refractory/relapsed hematologic malignancies and patients with breast cancer
      (Stages II-IV). Results from these trials demonstrate that stem cell
      transplantation with IL-2 activated stem cells (either PB or BM) with or without
      parenteral administration of IL-2 results in hematopoietic reconstitution with
      mild-to-moderate toxicities. This regimen also generates cutaneous and visceral
      autologous graft versus host disease (AuGVHD). The majority of our patients with
      relapsed/refractory hematologic malignancies or breast cancer developed either
      clinical and/or histological evidence of AuGVHD. Further studies are being
      conducted to determine if patients who develop AuGVHD experience improved disease
      free survival from a possible autologous graft versus tumor (GVT) effect. Current
      laboratory evaluations include the elucidation of the pathogenesis of AuGVHD and
      molecular evaluation of the purging efficacy of IL-2.

PMID- 8748005
TI  - Allogeneic peripheral blood stem cell transplantation.
AB  - The use of mobilized peripheral blood stem cells (PBSC) for hematopoietic
      reconstitution following myeloablative chemoradiotherapy has been well shown to
      be an effective and probably superior alternative to autologous bone marrow
      support. Early concerns of increased engraftment failure risk (owing to a
      decreased number of multipotential stem cells), increased graft vs. host disease
      risk (due to an excess of circulating T cells) and donor safety concerns,
      however, delayed efforts to use mobilized PBSC for allogeneic transplantation.
      Recent reports, however, have demonstrated excellent donor tolerance of G-CSF
      administration and yields of CD34+ progenitor cell collections. Engraftment with
      allogeneic peripheral blood stem cells has been rapid and sustained in several
      early clinical series. Surprisingly, no apparent increase in risk of moderate to
      severe acute graft versus host disease has occurred with unmanipulated mobilized
      PBSC. Despite this early promise, long-term safety concerns of administration of
      recombinant myeloid growth factors to normal donors have been raised. Long-term
      lymphohematopoietic engraftment also needs to be more conclusively demonstrated.
      Optimal mobilizing and collecting strategies also need to be defined to ensure
      donor safety and comfort. The possible roles of PBSC in the matched unrelated
      donor and mismatched related donor settings need to be defined before widespread
      adoption of mobilized PBSC as an alternative to bone marrow for allogeneic
      transplantation. Prospective randomized trials are recommended to definitively
      evaluate long term donor safety and recipient hematopoietic and immunologic
      reconstitution.

PMID- 8748006
TI  - Pilot study of ambulatory infusional delivery of a multidrug regimen: ifosfamide,
      carboplatin and etoposide (ICE).
AB  - PURPOSE: To determine the feasibility for administering ICE (ifosfamide,
      carboplatin, and etoposide) using an ambulatory infusional schedule for each of
      the three agents in a design that sequentially alternates those agents that are
      not compatible as an admixture. PATIENTS AND METHODS: Forty-one patients received
      ICE administered as follows: ifosfamide (500 mg/M2/day) without mesna days 1 to 7
      and 14 to 21; carboplatin (30 or 40 mg/M2/day) and etoposide (30 to 40 mg/M2/day)
      admixed as a single solution infused day 7 to 14. Patients were monitored weekly
      and cycles repeated at five-week intervals. RESULTS: Seventy-nine courses of
      therapy were analyzed. Forty-one patients received a median of two cycles with a
      range of one to five cycles. The only significant toxicity was hematologic with
      11 patients experiencing grade III neutropenia and 7 patients grade III
      thrombocytopenia (18%). Eleven patients did develop significant anemia requiring
      transfusion and/or the use of erythropoietin. Tumor responses were observed in 7
      of 24 evaluable patients, 4 of whom had lung cancer, 2 with small cell with no
      prior therapy and 2 with nonsmall cell with prior chemotherapy. CONCLUSION:
      Ambulatory infusion of ICE using an alternating sequence is feasible, and
      although the dose per cycle of carboplatin and etoposide is less than that of
      conventional bolus schedules for either single agent or combination programs, the
      ability to deliver this combination of agents in an ambulatory setting and
      without mesna substantially reduces the cost. Phase II studies of ambulatory
      infusion ICE in nonsmall cell lung cancer, lymphoma, and sarcoma are a reasonable
      next step.

PMID- 8748007
TI  - Pilot study of ambulatory infusional delivery of a multidrug regimen: cisplatin,
      5-fluorouracil and leucovorin (PFL) +/- etoposide.
AB  - PURPOSE: To determine the feasibility of ambulatory infusional administration 24
      hours per day, 7 days per week of a three-drug regimen of cisplatin or
      carboplatin, leucovorin, and 5-fluorouracil (5-FU) (PLF) utilizing an alternating
      weekly sequential design and to introduce infusional etoposide as PLEF to the
      regimen. PATIENTS AND METHODS: Forty-three patients with diverse malignancies
      received a sequential infusion of 5-FU 200 mg/M2/day on days 1 to 14 and 21 to 35
      with leucovorin admixed for day 1 to 7 and 21 to 28. Cisplatin (20 patients) or
      carboplatin (23 patients) infusion was administered at a dose of 10 mg/M2/day or
      30 mg/M2/day, respectively, day 7 to 14 and 35 to 42. Cycles were planned to be
      repeated consecutively in the absence of toxicity in patients with stable or
      responding disease. Sixteen patients also received etoposide 30 mg/M2/day as an
      admixture concomitant with administration of the platinum analogue. Therefore,
      the distribution of therapies was PLF 19, CLF 8, PLEF 14, and CLEF 2. RESULTS: A
      total of 63 courses of PLF +/- E was administered as outlined above. Hematologic
      toxicity was minimal with or without the addition of etoposide. Sixteen percent
      of patients developed an elevated creatinine with a median of 1.6 and a range of
      1.6 to 3.2 mg %. Tumor responses were observed in seven of fourteen evaluable
      patients with squamous cell carcinoma of the lung (all of whom received
      concomitant etoposide). In addition, one patient with metastatic gallbladder
      cancer achieved a complete clinical response. CONCLUSION: Ambulatory infusional
      PLF with carboplatin or cisplatin using sequentially alternating delivery of the
      component antineoplastic agents is feasible and active with minimal toxicity. The
      addition of infusional etoposide to the PLF regimen does not substantially
      increase hematologic toxicity. Extended phase II studies in aerodigestive cancers
      are ongoing and a phase III trial comparing this ambulatory regimen to short-term
      PLF infusion (5-day) may be justified to compare the relative cost and benefits
      of the two schedules.

PMID- 8748008
TI  - Ifosfamide seven-day infusion for recurrent and cisplatin refractory ovarian
      cancer.
AB  - BACKGROUND: The prognosis of advanced ovarian cancer is very poor, with about 15%
      of patients surviving at five years. Since most of these patients will relapse
      and/or progress while on therapy, effective salvage treatments are needed. A
      phase II trial was designed to evaluate the feasibility, toxicity, and response
      of a seven-day ambulatory continuous infusion of ifosfamide in patients with
      recurrent or chemoresistant advanced ovarian cancer. PATIENTS AND METHODS:
      Nineteen patients with progressive ovarian cancer following a cisplatin-based
      induction chemotherapy were treated with continuous infusion ifosfamide with
      mesna at 1 g/m2/d and 400 mg/m2/d, respectively, for seven days every 28 days.
      RESULTS: The overall response rate was 37%. Responses were observed both in
      patients who relapsed after induction chemotherapy (4/6) and in those who were
      resistant to cisplatin (3/13). Toxicity was mild and tolerable in these heavily
      pretreated patients. CONCLUSION: Ifosfamide, when administered as a protracted
      continuous infusion is an active drug in ovarian cancer and can be safely
      administered in an out-patient setting. Toxicity is minor even in heavily
      pretreated patients. Responses are observed in cisplatin refractory ovarian
      cancer.

PMID- 8748009
TI  - The present state of the art in chemotherapy for soft tissue sarcomas in adults:
      the EORTC point of view.

PMID- 8748010
TI  - Bleeding and thrombosis in myeloproliferative disorders: mechanisms and
      treatment.

PMID- 8748011
TI  - The biology of growth regulation in normal and malignant breast epithelium: from
      bench to clinic.

PMID- 8748012
TI  - Advances in the pathophysiology and treatment of thalassemia.

PMID- 8748013
TI  - Hematopoietic stem cells and microenvironment: the proliferation and
      differentiation of stromal cells.

PMID- 8748014
TI  - Diagnosis, treatment and pathophysiology of autoimmune thrombocytopenias.

PMID- 8748015
TI  - The coalescent process and background selection.
AB  - Some statistical properties of gene trees are described for a model with
      background deleterious mutations. It is argued that the history of a small sample
      of genes under this model is a continuous time Markov chain that quickly reaches
      stationarity. This observation leads to simple expressions for the expected
      nucleotide diversity and suggests that the frequency spectrum in small samples
      should be approximately the same as under a strict neutral model. The results
      concerning expected nucleotide diversity are compared with observed variation on
      the third chromosome of Drosophila melanogaster.

PMID- 8748016
TI  - Inferring population history from molecular phylogenies.
AB  - Variable molecular sequences sampled from a population can be used to infer its
      dynamic history. Graphical methods are developed and applied to real data,
      illustrating ways of navigating through hypothesis space with two landmarks for
      reference: constant population size and exponentially growing population size.

PMID- 8748017
TI  - Revealing the history of infectious disease epidemics through phylogenetic trees.
AB  - Phylogenetic trees play an increasing role in molecular epidemiology, where they
      have been used to understand the forces that shape patterns of viral sequence
      diversity. Phylogenetic trees can also be used to trace the dynamics of viral
      transmission within populations. Case studies document the worldwide spread of
      Human Immunodeficiency Virus type 1 (HIV-1) and hepatitis C virus (HCV). Despite
      similarities between these viruses, especially in their transmission routes, they
      are shown to have very different epidemiological histories. A possible reason for
      the difference is that HCV has coexisted longer with human populations.

PMID- 8748018
TI  - Cross-species transmission and recombination of 'AIDS' viruses.
AB  - Acquired Immune Deficiency Syndrome (AIDS) is caused by two different Human
      Immunodeficiency Viruses, HIV-1 and HIV-2. Closely related viruses (SIVs) are
      found in many species of non-human primates. Phylogenetic analyses indicate that
      cross-species transmission events have been quite frequent. Both HIV-1 and HIV-2
      appear to have resulted from multiple transfers of lentiviruses naturally
      infecting other primates; the source of HIV-2 appears to have been sooty
      mangabeys, whereas for HIV-1 the source may have been chimpanzees. Phylogenetic
      analyses also provide evidence that recombination has occurred between divergent
      viruses in vivo. Evolutionary trees based on various regions of the viral genome
      generally have consistent branching orders. However, some isolates fall into
      significantly different phylogenetic positions, indicating that their genomes are
      mosaics of sequences with different evolutionary histories. This implies that co
      infection with highly divergent viral strains can occur in HIV-infected humans
      and SIV-infected primates; this could lead to the generation of hybrid genomes
      with significantly altered biological properties, and also has important
      implications for HIV vaccine development programmes.

PMID- 8748019
TI  - Genealogies and geography.
AB  - Any sample of genes traces back to a single common ancestor. Each gene also has
      other properties: its sequence, its geographic location and the phenotype and
      fitness of the organism that carries it. With sexual reproduction, different
      genes have different genealogies, which gives us much more information, but also
      greatly complicates population genetic analysis. We review the close relation
      between the distribution of genealogies and the classic theory of identity by
      descent in spatially structured populations, and develop a simple diffusion
      approximation to the distribution of coalescence times in a homogeneous two
      dimensional habitat. This shows that when neighbourhood size is large (as in most
      populations) only a small fraction of pairs of genes are closely related, and
      only this fraction gives information about current rates of gene flow. The
      increase of spatial dispersion with lineage age is thus a poor estimator of gene
      flow. The bulk of the genealogy depends on the long-term history of the
      population; we discuss ways of inferring this history from the concordance
      between genealogies across loci.

PMID- 8748020
TI  - Molecular phylogenies and host-parasite cospeciation: gophers and lice as a model
      system.
AB  - Recent methodological advances permit a rigorous comparison of phylogenetic trees
      for hosts and their parasites to determine the extent to which these groups have
      cospeciated through evolutionary time. In cases where significant levels of
      cospeciation are indicated, comparison of amounts of evolutionary change that
      have accumulated along analogous branches in the host and parasite trees provides
      a direct assessment of relative rates of evolution in the two groups. For such a
      comparison to be meaningful, the features compared in the hosts and parasites
      should be genetically based, evolutionarily homologous, and should evolve in a
      roughly time-dependent fashion within each group. Nucleotide sequences encoding
      homologous genes in hosts and parasites are an ideal source of data for
      comparative studies of evolutionary rates. Recent studies of pocket gophers and
      their lice are used to illustrate the variety of questions that can be addressed
      through phylogenetic study of host-parasite systems.

PMID- 8748021
TI  - Phylogenies and comparative data, a microevolutionary perspective.
AB  - As species evolve along a phylogenetic tree, their phenotypes diverge. We expect
      closely related species to retain some phenotypic similarities owing to their
      shared evolutionary histories. The degree of similarity depends both on the
      phylogeny and on the detailed evolutionary changes that accumulate each
      generation. In this study, I review a general framework that can be used to
      translate between macroevolutionary patterns and the underlying microevolutionary
      process by comparing the observed relationships among measured species phenotypes
      and the expected relationship structure due to the phylogeny and underlying
      models of phenotypic evolution. I then show how the framework can be used to
      compare methods used (1) to reconstruct phylogenies, (2) to correct comparative
      data for phylogenetic non-independence, and (3) to infer details of the
      microevolutionary process from interspecific data and a phylogeny. Use of this
      framework and a microevolutionary perspective on the analysis of interspecific
      data opens up new fields of inquiry and many new uses for phylogenies and
      comparative data.

PMID- 8748022
TI  - Uses for evolutionary trees.
AB  - The general impression of molecular evolution is often that one sequences a gene
      from a number of organisms and infers the evolutionary relations of the
      organisms. Indeed, if the sequences turn out to be orthologous and the data
      robust, one will get a phylogeny (tree) depicting those historical relations. But
      what one really obtains is a gene tree (I shall henceforth assume that the data
      are robust; that is another problem) and the biological messages implicit in that
      tree can be quite various. This article lists a number of those messages that one
      may have or may wish to look for.

PMID- 8748023
TI  - Quelling the red menace: haem capture by bacteria.
AB  - Haem is an important bacterial nutrient. As a prosthetic group of several
      proteins, haem functions as a cofactor mediating oxygen transport, energy
      generation, and mixed-function oxidation. In addition, the iron chelated in the
      porphyrin ring may serve as an iron substrate for growth. However, because of its
      propensity for oxidizing cellular constituents, haem is always associated with
      proteins. Therefore, the uptake and transit of haem across bacterial membranes
      requires the participation of protein escorts. Bacteria have evolved a diverse
      array of surface-exposed receptors dedicated to binding haem and haem-proteins.
      Following this selective recognition at the bacterial cell surface, haem is
      transported across the outer membrane via a TonB-dependent process. The control
      of receptor expression appears to be multifactorial, probably involving a number
      of global regulators. A model integrating this information is presented.

PMID- 8748024
TI  - Molecular cloning, sequence analysis, and functional characterization of the
      lipopolysaccharide biosynthetic gene kdtA encoding 3-deoxy-alpha-D-manno
      octulosonic acid transferase of Chlamydia pneumoniae strain TW-183.
AB  - The gene kdtA of Chlamydia pneumoniae strain TW-183, encoding the enzyme 3-deoxy
      alpha-D-manno-octulosonic acid (Kdo) transferase of lipopolysaccharide
      biosynthesis, was cloned and sequenced. A single open reading frame of 1314 bp
      was identified, the deduced amino acid sequence of which revealed 69% similarity
      and 43% identity with KdtA of Chlamydia trachomatis and Chlamydia psittaci. The
      gene was expressed in the Gram-positive host Corynebacterium glutamicum and the
      primary gene product was characterized as a multifunctional glycosyltransferase.
      Cell-free extracts generated in vitro the genus-specific epitope of Chlamydia
      composed of the trisaccharide alphaKdo(2-8)alphaKdo(2-4)alphaKdo. The results
      show that a single polypeptide affords three different glycosidic bonds, which is
      in contradiction to the dogma of glycobiology: 'one enzyme - one glycosidic
      bond'.

PMID- 8748025
TI  - Membrane glycerophospholipid biosynthesis in Neisseria meningitidis and Neisseria
      gonorrhoeae: identification, characterization, and mutagenesis of a
      lysophosphatidic acid acyltransferase.
AB  - Lysophosphatidic acid (LPA) acyltransferases of Neisseria meningitidis and
      Neisseria gonorrhoeae were identified which share homology with other prokaryotic
      and eukaryotic LPA acyltransferases. In Escherichia coli, the conversion of LPA
      to phosphatidic acid, performed by the 1-acyl-sn-glycerol-3-phosphate
      acyltransferase PlsC, is a critical intermediate step in the biosynthesis of
      membrane glycerophospholipids. A Tn916-generated mutant of a serogroup B
      meningococcal strain was identified that exhibited increased amounts of capsular
      polysaccharide, as shown by colony immunoblots, and a threefold increase in the
      number of assembled pili. The single, truncated 3.8 kb Tn916 insertion in the
      meningococcal mutant was localized within a 771 bp open reading frame, The
      gonococcal equivalent of this gene was identified by transformation with the
      cloned meningococcal mutant gene. In N. gonorrhoeae, the mutation increased
      piliation fivefold. The insertions were found to be within a gene that was
      subsequently designated nlaA (neisserial LPA acyltransferase). The predicted
      neisserial LPA acyltransferases were homologous (>20% identity, >40% amino acid
      similarity) to the family of PlsC protein homologues. A cloned copy of the
      meningococcal nlaA gene complemented in trans a temperature-sensitive E. coli
      PlsCts- mutant. Tn916 and omega-cassette insertional inactivations of the
      neisserial nlaA genes altered the membrane glycerophospholipid compositions of
      both N. meningitidis and N. gonorrhoeae but were not lethal. Therefore, the
      pathogenic Neisseria spp. appear to be able to utilize alternative enzyme(s) to
      produce phosphatidic acid. This hypothesis is supported by the observation that,
      although the amounts of mature glycerophospholipids were altered in the
      meningococcal and the gonococcal nlaA mutants, glycerophospholipid synthesis was
      detectable at significant levels. In addition, acyltransferase enzymatic
      activity, while reduced in the gonococcal nlaA mutant, was increased in the
      meningococcal nlaA mutant. We postulate that the pathogenic Neisseria spp. are
      able to utilize alternate acyltransferases to produce glycerophospholipids in the
      absence of nlaA enzymatic activity. Implementation of these secondary enzymes
      results in alterations of glycerophospholipid composition that lead to
      pleiotropic effects on the cell surface components, including effects on capsule
      and piliation.

PMID- 8748026
TI  - The unrelated surface proteins ActA of Listeria monocytogenes and IcsA of
      Shigella flexneri are sufficient to confer actin-based motility on Listeria
      innocua and Escherichia coli respectively.
AB  - Listeria monocytogenes and Shigella flexneri are two unrelated facultative
      intracellular pathogens which spread from cell to cell by using a similar mode of
      intracellular movement based on continuous actin assembly at one pole of the
      bacterium. This process requires the asymmetrical expression of the ActA surface
      protein in L. monocytogenes and the IcsA (VirG) surface protein in S. flexneri.
      ActA and IcsA share no sequence homology. To assess the role of the two proteins
      in the generation of actin-based movement, we expressed them in the genetic
      context of two non-actin polymerizing, non-pathogenic bacterial species, Listeria
      innocua and Escherichia coli. In the absence of any additional bacterial
      pathogenicity determinants, both proteins induced actin assembly and propulsion
      of the bacteria in cytoplasmic extracts from Xenopus eggs, as visualized by the
      formation of characteristic actin comet tails. E. coli expressing IcsA moved
      about two times faster than Listeria and displayed longer actin tails. However,
      actin dynamics (actin filament distribution and filament half-lives) were similar
      in IcsA- and ActA-induced actin tails suggesting that by using unrelated surface
      molecules, L. monocytogenes and S. flexneri move intracellularly by interacting
      with the same host cytoskeleton components or by interfering with the same host
      cell signal transduction pathway.

PMID- 8748027
TI  - The amino-terminal part of ActA is critical for the actin-based motility of
      Listeria monocytogenes; the central proline-rich region acts as a stimulator.
AB  - The intracellular bacterial pathogen Listeria monocytogenes moves inside the host
      cell cytoplasm propelled by continuous actin assembly at one pole of the
      bacterium. This process requires expression of the bacterial surface protein
      ActA. Recently, in order to identify the regions of ActA which are required for
      actin assembly, we and others have expressed different domains of ActA by
      transfection in eukaryotic cells. As this type of approach cannot address the
      role of ActA in the actin-driven bacterial propulsion, we have now generated
      several L. monocytogenes strains expressing different domains of ActA and
      analysed the ability of the different domains to trigger actin assembly and
      bacterial movement in both infected cells and cytoplasmic extracts. We show here
      that the amino-terminal part is critical for F-actin assembly and movement. The
      internal proline-rich repeats and the carboxy-terminal domains are not essential.
      However, in vitro motility assays have demonstrated that mutants lacking the
      proline-rich repeats domain of ActA moved two times slower (6+/-2 micrometers
      min(-1)) than the wild type (13 +/-3 micrometers min(-1)). In addition,
      phosphatase treatment of protein extracts of cells infected with the L.
      monocytogenes strains expressing the ActA variants suggested that phosphorylation
      may not be essential for ActA activity.

PMID- 8748028
TI  - Deletion mutagenesis of Tn 10 Tet repressor--localization of regions important
      for dimerization and inducibility in vivo.
AB  - The gene for the Tn 10 Tet repressor (TetR) was subjected to deletion
      mutagenesis. Screening for a transdominant operator-binding negative phenotype
      yielded 10 mutants with internal deletions. Three deletions extend from residue
      D5 to residues L41, W75, or Q76, respectively, and two contain deletions of the
      alpha-helix-turn-alpha-helix DNA-binding motif. Five deletions range from residue
      K84 to residues between R87 and K98. Since residues from the N-terminus up to
      position 98 are not necessary for dimerization, this must take place in the C
      terminal half of the protein. Ability to dimerize was probed by introducing ochre
      nonsense codons (oc) at residues G138, H151, E159, I174, or K202. Koc202 shows
      wild-type in vivo operator-binding and inducibility by tetracycline indicating
      that the six C-terminal residues of TetR are not important for activity. Mutants
      with longer C-terminal truncations are inactive and not transdominant. They show
      reduced steady-state protein levels and are probably impaired in folding and
      degraded in vivo. Two mutants (delta151-166, delta164-166) with deletions in a
      region variable in primary structure and length among Tet repressors from
      different resistance determinants bind tet operator efficiently, but are not
      inducible by tetracycline. This result indicates that these residues are not
      important for dimer formation in the operator-binding form.

PMID- 8748029
TI  - The Flp recombinase cleaves Holliday junctions in trans.
AB  - The Flp site-specific recombinase is encoded by the 2 micrometers plasmid
      Saccharomyces cerevisiae and is a member of the integrase family of recombinases.
      Like all members of the integrase family studied, Flp mediates recombination in
      two steps. First, a pair of strand exchanges creates a Holliday-like
      intermediate; second, this intermediate is resolved to recombinant products by a
      second pair of strand exchanges. Evidence derived from experiments using linear
      substrates indicates that Flp's active site is composed of two Flp protomers. One
      binds to the Flp recognition target site (FRT site) and activates the scissile
      phosphodiester bond for cleavage. Another molecule of Flp bound elsewhere in the
      synaptic complex (in trans) donates the nucleophilic tyrosine that executes
      cleavage and thereby becomes covalently attached to the 3' phosphoryl group at
      the cleavage site. It has previously been shown that Flp efficiently resolves
      synthetic, Holliday-like (chi) structures to linear products. In this paper, we
      examined whether resolution of chi structures by Flp also occurs via the trans
      cleavage mechanism. We used in vitro complementation studies of mutant Flp
      proteins as well as nicked chi structures to show that Flp resolves chi
      structures by trans cleavage. We propose a model for Flp-mediated recombination
      that incorporates trans cleavage at both the initial and resolution steps of
      strand exchange.

PMID- 8748030
TI  - Visualization of the subcellular location of sporulation proteins in Bacillus
      subtilis using immunofluorescence microscopy.
AB  - We describe the application of immunofluorescence microscopy to visualization of
      the subcellular localization of proteins involved in coat morphogenesis and
      chromosome packaging during the process of sporulation in Bacillus subtilis. In
      confirmation and extension of previous findings, we show that SpolVA, which is
      responsible for guiding coat formation to the surface of the outer membrane that
      surrounds the developing spore, assembles into a shell that is located close to
      or on the surface of this enveloping membrane. CotE, which is responsible for the
      formation of the outer layer of the coat, assembles into a second shell of
      apparently larger diameter. Assembly of SpolVA could be detected as early as the
      morphological stage of polar septation and closely followed the enveloping
      membrane of the mother cell during the stage of engulfment, thereby providing a
      sensitive and diagnostic marker for this phagocytic-like process. Surprisingly,
      the chromosome of the developing spore and the small, acid-soluble proteins,
      known as alpha/beta-type SASPs, that are known to coat the spore chromosome, were
      found to co-localize to a doughnut-like ring of approximately 1 micrometer in
      diameter. The use of a double mutant lacking the alpha/beta-type SASP
      demonstrated that these high abundance, DNA-binding proteins are responsible for
      packaging the chromosome of the developing spore into this unusual structure. We
      conclude that sporulation in B. subtilis is a fertile system for addressing cell
      biological problems in a bacterium and that immunofluorescence microscopy
      provides a sensitive method for visualizing protein subcellular localization at
      high resolution.

PMID- 8748031
TI  - The role of chromatin-associated protein Hbsu in beta-mediated DNA recombination
      is to facilitate the joining of distant recombination sites.
AB  - The beta recombinase is unable to mediate in vitro DNA recombination between two
      directly oriented recombination sites unless a bacterial chromatin-associated
      protein (Bacillus subtilis Hbsu or Escherichia [correction of Eschrichia] coli
      HU] is provided. By electron microscopy, we show that the role of Hbsu is to help
      in joining the recombination sites to form a stable synaptic complex. Some
      evidence supports the fact that Hbsu works by recognizing and stabilizing a DNA
      structure at the recombination site, rather than by serving as a bridge between
      beta recombinase dimers through a protein-protein interaction. We show that the
      mammalian HMG1 protein, which shares neither sequence nor structural homology
      with Hbsu, can also stimulate beta-mediated recombination. These chromatin
      associated proteins share the property of binding to DNA in a relatively non
      specific fashion, bending it, and having a marked preference for altered DNA
      structures. Hbsu, HU or HMG1 proteins probably bind specifically at the crossing
      over region, since at limiting protein-DNA molar ratios they could not be
      outcompeted by an excess of a DNA lacking the crossing over site. Distamycin, a
      minor groove binder that induces local distortions in DNA, did not affect the
      binding of beta protein to DNA, but inhibited the formation of the synaptic
      complex.

PMID- 8748032
TI  - Salmonella typhimurium secreted invasion determinants are homologous to Shigella
      Ipa proteins.
AB  - Salmonella typhimurium secreted proteins (Ssp) were previously implicated in
      epithelial cell invasion. Here we describe four genes (SspB, sspC, sspD, and
      sspA), located between spaT and prgH, which encode proteins of 63, 42, 36, and 87
      kDa, respectively. These Ssp are homologous to Shigella flexneri secreted
      proteins IpaB, IpaC, IpaD and IpaA. A non-invasive mutant with a transposon
      insertion in sspC lacks Ssp of 87, 42 and 36 kDa. Complementation and analyses
      show that sspC and sspD encode the 42 and the 36 kDa Ssp, while the 87 kDa Ssp is
      encoded by sspA. sspC and sspD, but not sspA, are required for invasion. Amino
      terminal sequencing shows that SspC and SspA are secreted without amino-terminal
      processing. We further demonstrate that Ssp secretion requires proteins encoded
      by prgHIJK, homologous to the Shigella Ipa secretion system, since SspA is
      abundantly secreted by wild-type bacteria but is completely retained within the
      cellular fraction of a prgHIJK mutant. A precipitate containing abundant SspC and
      three other major Ssp of 63, 59 and 22 kDa was isolated from culture supernatants
      of wild-type bacteria. These data indicate that major secreted invasion
      determinants of S. typhimurium are structurally and functionally homolgous to S.
      flexneri Ipa proteins.

PMID- 8748033
TI  - Mutational activation of the Cpx signal transduction pathway of Escherichia coli
      suppresses the toxicity conferred by certain envelope-associated stresses.
AB  - The processing-defective outer membrane porin protein LamBA23D (Carlson and
      Silhavy, 1993) and a tripartite fusion protein, LamB-LacZ-PhoA (Snyder and
      Silhavy, 1995), are both secreted across the cytoplasmic membrane of Escherichia
      coli, where they exert an extracytoplasmic toxicity. Suppressors of these
      toxicities map to a previously characterized gene, cpxA, that encodes the sensor
      kinase protein of a two-component regulatory system. These activated cpxA
      alleles, designated as cpxA*, stimulate transcription of the periplasmic protease
      DegP (Danese et al., 1995), which in turn catalyses degradation of the tripartite
      fusion protein. In contrast, degradation of precursor LamBA23D is not
      significantly stimulated in a cpxA* suppressor background. In fact, increased
      levels of DegP in a wild-type background stabilized this protein. While a
      functional degP gene is required for full cpxA*-mediated suppression of both
      toxic envelope proteins, residual suppression is seen in cpxA* degP::Tn10 double
      mutants. Furthermore, cpxA* mutations suppress the toxicity conferred by the LamB
      LacZ hybrid protein, which exerts its effects in the cytoplasm, sequestered from
      DegP. Together, these observations suggest that the activated Cpx pathway
      regulates additional downstream targets that contribute to suppression. A subset
      of these targets may constitute a regulon involved in relieving extracytoplasmic
      and/or secretion-related stress.

PMID- 8748034
TI  - Evidence for in vivo but not in vitro expression of a Borrelia burgdorferi outer
      surface protein F (OspF) homologue.
AB  - Protein export signals from the low-passage 297 strain of Borrelia burgdorferi
      were cloned as fusions with an Escherichia coli alkaline phosphatase (PhoA)
      reporter lacking a signal sequence. One PhoA+ clone (BbK2.10-PhoA) was derived
      from a borrelial lipoprotein. Although the polypeptide encoded by the full-length
      bbk2.10 gene had 76% similarity and 56% identity to outer surface protein F
      (OspF) from B. burgdorferi strain N40, antibodies directed against recombinant
      forms of the two proteins revealed that they were not cross-reactive. The
      nucleotide sequences of bbk2.10 and ospF from the N40 and 297 strains,
      respectively, were determined to confirm that the N40 and 297 strains each
      contained both genes. Southern blot analysis revealed that bbk2.10 is a single
      copy gene and that the B. burgdorferi strain 297 and N40 genomes appeared to
      contain one other gene more closely related to ospF than bbk2.10. It was
      particularly noteworthy that ospF, but not bbk2.10, was expressed in vitro while
      B. burgdorferi-infected mice generated antibodies reactive with both
      lipoproteins. To help confirm that the BbK2.10-reactive antibodies produced by
      the B. burgdorferi-infected mice were specific for that protein, a second gene,
      bbk2.11, which hybridized with the ospF probe was cloned; the corresponding
      polypeptide reacted strongly with OspF antisera but failed to react with BbK2.10
      specific antisera. Taken together, these data demonstrate that BbK2.10, BbK2.11,
      and OspF comprise a B. burgdorferi lipoprotein family and that at least one
      member (BbK2.10) appears to be expressed only during infection.

PMID- 8748035
TI  - Transcriptional co-activation at the ansB promoters: involvement of the
      activating regions of CRP and FNR when bound in tandem.
AB  - Previous work with semi-synthetic promoters containing a single CRP binding site
      centred at 41.5 bp from the transcription start site has demonstrated enhanced
      transcription (synergism) when a second binding site, for CRP or FNR, is placed
      upstream at around -91 bp. The ansB promoter in Escherichia coli is co-activated
      in a co-dependent manner by one dimer each of CRP and FNR protein whose binding
      sites are at around -91 and -41 bp, respectively, from the transcription start
      site. Similarly, the homologous ansB promoter in Salmonella is co-activated by
      two dimers of CRP which function synergistically. The binding sites at the E.
      coli promoter have been changed by mutation to provide a number of active
      promoter derivatives carrying other combinations of FNR and CRP binding sites.
      The co-dependent versus synergistic interaction of these activators and their
      requirement for known activating regions have been examined. The results
      demonstrate that FNR can co-activate when located upstream at around -91 bp in
      combination with either FNR or CRP downstream. When FNR occupies the downstream
      site the promoter is co-dependent on an upstream activator, but not when CRP
      occupies this site. Activating region 1 in CRP (defined by substitutions at
      residue H159) and its putative equivalent in FNR (defined by substitutions at
      S73) are mainly required in the upstream activator; the putative equivalent in
      FNR of activating region 3 of CRP (defined by substitutions at G85 and K52,
      respectively) is mainly required in the dimer which binds downstream. Activating
      region 1 of FNR is required only in the downstream subunit of the upstream
      activator in a promoter which is co-dependent on two FNR dimers. These data
      suggest that both bound upstream and downstream activators interact with RNA
      polymerase to promote transcription, and that co-dependence is determined by the
      nature of the activator plus the promoter context.

PMID- 8748036
TI  - Regulation of anaerobic citrate metabolism in Klebsiella pneumoniae.
AB  - Three enzymes are specifically required for uptake and catabolism of citrate by
      Klebsiella pneumoniae under anaerobic conditions: a Na+ -dependent citrate
      carrier (CitS), citrate lyase (CitDEF), and the Na+ pump oxaloacetate
      decarboxylase (OadGAB). The corresponding genes are clustered on the chromosome,
      with the citCDEFG genes located upstream and divergent to the citS-oadGAB genes.
      We found that expression of citS from its native promoter in Escherichia coli
      requires the DNA region downstream of oadB. Nucleotide sequence analysis of this
      region revealed the presence of two adjacent genes, citA and citB. By sequence
      similarity, the predicted CitA and CitB proteins were identified as members of
      the two-component regulatory systems. The sensor kinase CitA contained, in the N
      terminal half, two putative transmembrane helices which enclosed a presumably
      periplasmic domain of about 130 amino acids. The C-terminal half of the response
      regulator CitB harboured a helix-turn-helix motif typical of DNA-binding
      proteins. K. pneumoniae citB null mutants were unable to grow anaerobically with
      citrate as the sole carbon and energy source (Cit- phenotype). When cultivated
      anaerobically with citrate plus glycerol, all of the citrate-specific
      fermentation enzymes were synthesized in the wild type, but not in the citB
      mutants. This showed that citS, oadGAB and citDEF required the CitB protein for
      expression and therefore are part of a regulon. In the wild type, synthesis of
      CitS, oxaloacetate decarboxylase and citrate lyase was dependent on the presence
      of citrate, sodium ions and a low oxygen tension. In a citA null mutant which
      expressed citB constitutively at high levels, none of these signals was required
      for the formation of the citrate fermentation enzymes. This result suggested that
      citrate, Na+, and oxygen exerted their regulatory effects via the CitA/CitB
      system. In the presence of these signals, the citAB gene products induced their
      own synthesis. The positive autoregulation occurred via co-transcription of citAB
      with citS and oadGAB.

PMID- 8748037
TI  - Genetic and functional evidence that Type IV pili are required for social gliding
      motility in Myxococcus xanthus.
AB  - The social gliding behaviour of Myxococcus xanthus has previously been associated
      with the presence of polar pili. A Tn5 transposon insertion was isolated which
      introduces a defect in social gliding and is genetically linked to a known sgl
      locus; this insertion was found also to cause a piliation defect. A 2.7 kb
      section of DNA was isolated from either side of this transposon and sequenced,
      revealing three genes which encode amino acid sequences with substantial
      similarity to components of the Type IV pilus biogenesis pathway in Pseudomonas
      aeruginosa. The myxococcal pilA gene encodes a putative pilin precursor with a
      short signal sequence and processing site similar to those of other Type IV
      pilins. Myxococcal pilS and pilR encode amino acid sequences with similarity to
      PilS and PilR of P. aeruginosa, as well as to other members of the NtrB/C family
      of two-component regulators. Mutations within pilR and pilA that have no polar
      effect were demonstrated to be responsible for pilus and social motility defects.
      These results indicate that the pili of M. xanthus belong to the Type IV family
      of pili, and demonstrate that these pili are actually required for social
      motility.

PMID- 8748038
TI  - Uptake of inorganic carbon in the cyanobacterium Synechocystis PCC6803:
      physiological and genetic evidence for a high-affinity uptake system.
AB  - Synechocystis PCC6803 displays two inorganic carbon-uptake processes, a low
      affinity one (apparent Km: 300-400 microM) functional in cells grown under
      standard or limiting inorganic carbon concentrations, and one with a higher
      affinity (60 +/- 12 microM), detected only in cells adapted to limiting inorganic
      carbon conditions. A mutational and screening procedure allowed the isolation of
      a mutant deficient in the high-affinity system, but only slightly impaired in its
      growth capacities. The mutated genomic region revealed two open reading frames
      (ORFs), possibly belonging to an operonic structure. A clone in which the
      downstream ORF, hatR (high-affinity transport), had been inactivated showed a
      phenotype close to that of the original mutant. Inactivation of the other ORF,
      hatA, yielded a clone unable to grow in limiting inorganic carbon conditions. The
      deduced HatA protein showed no homology with any registered protein. It possessed
      three hydrophobic domains, including a putative signal peptide. Several
      hypotheses are considered as to its role. The deduced HatR protein, which
      possessed the features characteristic of the response regulators of the two
      component regulatory systems ubiquitous in bacteria, might be a regulator
      controlling the activity of the high-affinity transport process. It would belong
      to the subclass of these molecules lacking the DNA-binding domain.

PMID- 8748039
TI  - Identification of a plasminogen-binding motif in PAM, a bacterial surface
      protein.
AB  - Surface-associated plasmin(ogen) may contribute to the invasive properties of
      various cells. Analysis of plasmin(ogen)-binding surface proteins is therefore of
      interest. The N-terminal variable regions of M-like (ML) proteins from five
      different group A streptococcal serotypes (33, 41, 52, 53 and 56) exhibiting the
      plasminogen-binding phenotype were cloned and expressed in Escherichia coli. The
      recombinant proteins all bound plasminogen with high affinity. The binding
      involved the kringle domains of plasminogen and was blocked by a lysine analogue,
      6-aminohexanoic acid, indicating that lysine residues in the M-like proteins
      participate in the interaction. Sequence analysis revealed that the proteins
      contain common 13-16-amino-acid tandem repeats, each with a single central lysine
      residue. Experiments with fusion proteins and a 30-amino-acid synthetic peptide
      demonstrated that these repeats harbour the major plasminogen-binding site in the
      ML53 protein, as well as a binding site for the tissue-type plasminogen
      activator. Replacement of the lysine in the first repeat with alanine reduced the
      plasminogen-binding capacity of the ML53 protein by 80%. The results precisely
      localize the binding domain in a plasminogen surface receptor, thereby providing
      a unique ligand for the analysis of interactions between kringles and proteins
      with internal kringle-binding determinants.

PMID- 8748040
TI  - nasST, two genes involved in the induction of the assimilatory nitrite-nitrate
      reductase operon (nasAB) of Azotobacter vinelandii.
AB  - An operon including two new genes (nasS and nasT) has been defined, cloned and
      sequenced. The deduced NASS protein is homologous to NRTA from Synechococcus sp.
      and to NASF from Klebsiella pneumoniae, two proteins involved in nitrate uptake.
      The predicted NAST polypeptide is homologous to the regulator proteins of the two
      component regulatory systems. NASS plays a negative regulatory role in the
      synthesis of the nitrate and nitrite reductase. NAST is required for the
      expression of the nitrite-nitrate reductase operon (nasAB). Expression of the
      nasST operon is not under the control of the NTR system and is not regulated by
      the nitrogen source. A Phi(nasA-lacZ) fusion has been used to analyse expression
      of the nasAB operon in three different genetic backgrounds with altered nitrate
      reductase activity. Beta-galactosidase activity in two of them was independent of
      nitrate but in a mutant unable to reduce nitrate, nas-4, it was normally induced
      by nitrate.

PMID- 8748041
TI  - Risperidone in the treatment of negative symptoms of schizophrenia: a meta
      analysis.
AB  - Risperidone has antiserotonergic and antidopaminergic properties that may make it
      more effective than conventional antipsychotic agents in the treatment of the
      negative symptoms of schizophrenia. Clinical trials in chronic schizophrenic
      patients have shown trends in favor of risperidone in the control of negative
      symptoms compared with haloperidol, perphenazine or zuclopenthixol, but the
      differences were not consistently statistically significant. A meta-analysis of
      the pooled results from six double-blind trials showed that risperidone at doses
      ranging from 4 to 8 mg/day had a significantly (p < 0.004) higher negative
      symptom response rate, defined as the percentage of patients with a 20% or more
      reduction in scores on the negative subscale of the Positive and Negative
      Syndrome Scale, than patients receiving active controls. The combined patient
      population treated with 4-8 mg/day of risperidone was 1.43 times more likely to
      have had a clinical response on the negative symptom subscale than the combined
      population treated with haloperidol, perphenazine or zuclopenthixol.

PMID- 8748042
TI  - Do the endocrine and subjective effects of d-fenfluramine predict response to
      selective serotonin reuptake inhibitors?
AB  - Thirty drug-free depressed patients underwent double-blind, placebo-controlled,
      neuroendocrine testing with the serotonin (5-HT) releasing agent d-fenfluramine
      prior to receiving treatment with a selective serotonin reuptake inhibitor (SSRI)
      for 8 weeks. Compared to placebo, d-fenfluramine significantly elevated plasma
      levels of prolactin and cortisol, increased subjective visual analogue ratings of
      "light headed" and decreased ratings of "desire to eat". Of the 30 patients
      studied, 17 responded to treatment but none of the pretreatment responses to d
      fenfluramine distinguished patients who responded to SSRI treatment from those
      who did not. The results suggest that the clinical response to SSRI
      administration may be independent of pretreatment brain 5-HT function. Another
      possibility is that the neuroendocrine and subjective effects of d-fenfluramine
      are mediated by 5-HT mechanisms other than those involved in the antidepressant
      effect of SSRIs.

PMID- 8748043
TI  - Central D2 receptor occupancy and effects of zuclopenthixol acetate in humans.
AB  - Repeated positron emission tomography (PET) measurements of D2 receptor
      occupancy, plasma concentrations of zuclopenthixol and reaction time were
      performed in three healthy subjects after injection of 12.5 mg zuclopenthixol
      acetate (ZPTA) in an open study design. Five control subjects were examined for
      reaction time only. D2 receptor occupancy was 51%, 71% and 75% after 7 h and 75%,
      83% and 87% after 31 h in the three subjects. The subjects reported sedation, but
      reaction time was not prolonged. After the low dose of 12.5 mg ZPTA, D2 receptor
      occupancy exceeded the 70% assumed to be required to induce antipsychotic effect.
      Extrapolation of data to a clinical dose interval indicates that 50-150 mg ZPTA
      should induce very high D2 receptor occupancy lasting several days after
      injection. Such high doses may be required to induce sedation and to avoid
      frequent intramuscular injections in acutely psychotic patients. However, the
      simultaneously induced very high D2 receptor occupancy calls for careful
      assessment of acute extrapyramidal symptoms.

PMID- 8748044
TI  - A comparison of the effects of phenelzine treatment with moclobemide treatment on
      cardiovascular reflexes.
AB  - The effects of treatment with phenelzine (n = 15) and moclobemide (n = 20) on
      heart rate variability and cardiovascular responses to standing were examined
      using non-invasive beat-to-beat blood pressure (BP) monitoring in an open cross
      sectional study. Phenelzine markedly impaired the BP response compared with
      moclobemide, with 83% vs 15% of patients lacking the normal initial BP overshoot
      (p < 0.01). BP recovery to supine levels was delayed (median time for diastolic
      BP 14.5 s after phenelzine vs 4.9 s after moclobemide; p < 0.002). Standing BP at
      1 min and its change from supine levels were also significantly lower in the
      phenelzine group (delta diastolic BP 4 mmHg vs 15 mmHg; p < 0.001). Heart rate
      responses and variability were preserved and did not differ between treatments.
      These findings are consistent with impairment of sympathetic function but
      preservation of parasympathetic responses after phenelzine treatment.

PMID- 8748045
TI  - First clinical experience with olanzapine (LY 170053): results of an open-label
      safety and dose-ranging study in patients with schizophrenia.
AB  - Although neuroleptic drugs have proven value in the management of patients with
      schizophrenia, the existing drugs are far from ideal. The pharmacological profile
      of olanzapine (LY 170053, Lilly) in animal models suggests that it may be an
      effective antipsychotic drug in humans, with the potential for a reduced
      incidence of desirable extra-pyramidal side effects, compared to existing
      neuroleptics. The results of this first investigation of olanzapine in
      schizophrenic patients indicate that it has efficacy as an antipsychotic
      compound, relieving positive and negative features of schizophrenia. Olanzapine
      appears to have an acceptable degree of overall tolerability, and may be
      associated with a low incidence of extrapyramidal tract symptoms. It does not
      appear to be free of adverse effects on liver function.

PMID- 8748046
TI  - Naloxone and metergoline effects on growth hormone response to gamma
      hydroxybutyric acid.
AB  - Gamma-hydroxybutyric acid (GHB) has been recently used in alcohol detoxification,
      but conflicting data are available concerning the central mechanism of action of
      this GABA catabolite. GHB ability to stimulate growth hormone (GH) secretion has
      been reported. Our previous studies revealed the ability of flumazenil (a
      benzodiazepine antagonist) to counteract GHB effects on GH secretion. Other
      hypotheses, including an opioid or serotonergic role of GHB, have been
      considered. In the present study we investigated GH responses to GHB with or
      without naloxone (an opiate receptor antagonist) or metergoline (a serotonin
      receptor antagonist) pretreatment. This study included 10 male healthy volunteers
      (aged 24.3 +/- 2.9 years) who were submitted to four tests in random order: (A)
      oral GHB administration; (B) oral GHB and i.v. naloxone administration; (C) oral
      GHB and oral metergoline administration; and (D) oral placebo and i.v. saline
      administration. Blood samples for GH assay were collected during the three tests
      at -15, 0, 15, 30, 45, 60 and 90 min. GHB induced a significant increase in GH
      plasma levels; naloxone pretreatment did not antagonize GHB action on GH
      secretion; metergoline significantly decreased GH response to GHB (p < 0.05). No
      changes were obtained with placebo and saline administration. The opioid system
      does not seem to be involved in GHB effects on GH-secreting pituitary cells; GHB
      effects on the serotonergic system influencing GH secretion, on the other hand,
      cannot be excluded.

PMID- 8748047
TI  - Placebo-controlled comparison of the clinical effects of rapid discontinuation of
      ipsapirone and lorazepam after 8 weeks of treatment for generalized anxiety
      disorder.
AB  - One hundred and sixty patients (mean age 39.8 years; 67% female) diagnosed with
      generalized anxiety disorder (GAD) who had completed a prospective, 8 week,
      double-blind comparison of lorazepam (mean daily dose 4.2 mg) and ipsapirone
      (mean daily dose 19.5 mg) were rapidly tapered by a substitution of half-strength
      medication for 3 days, then substitution of matched placebo for an additional 11
      days. Patients treated with ipsapirone showed no rebound anxiety on
      discontinuation, nor any other significant increase in withdrawal symptomatology
      compared to patients who had been prospectively treated with placebo. In
      contrast, patients treated with lorazepam showed significant emergent anxiety
      and/or withdrawal-related symptomatology by almost all clinical measures
      employed. Overall, 25% of patients treated with lorazepam showed rebound anxiety,
      and 40% of them utilized reserve medication because they found drug
      discontinuation to be intolerable. The clinical implications for discontinuation
      of benzodiazepines after short-term therapy are discussed.

PMID- 8748048
TI  - Akathisia-like behavior following ECT, and its successful treatment with low-dose
      mianserin.
AB  - The development of akathisia-like behavior during a course of electroconvulsive
      therapy (ECT) in a patient with psychotic depression is described. The ECT
      induced akathisia responded successfully to mianserin. It seems that the
      beneficial effect of low-dose mianserin (15 mg/day) is related to its prominent
      antagonistic activity at the 5-HT2A/5-HT2C receptors.

PMID- 8748049
TI  - Lithium-induced akathisia responds to low-dose mianserin: case report.
AB  - A case of acute akathisia induced by lithium treatment is described. Since
      lithium administration leads to activation of serotonergic neurotransmission, the
      5-HT2A/2C and 5-HT3 antagonist mianserin was added as a possible anti-akathitic
      agent. Mianserin treatment (15 mg/day at 21.00 h) resulted in amelioration of the
      lithium-induced akathisia.

PMID- 8748050
TI  - Encephalopathy during amitriptyline therapy: are neuroleptic malignant syndrome
      and serotonin syndrome spectrum disorders?
AB  - This report describes a case of encephalopathy developed in the course of
      amitriptyline therapy, during a remission of unipolar depression. This patient
      could have been diagnosed as having either neuroleptic malignant syndrome (NMS)
      or serotonin syndrome (SS). The major determinant of the symptoms may have been
      dopamine/serotonin imbalance in the central nervous system. The NMS-like
      encephalopathy that develops in association with the use of antidepressants
      indicates that NMS and SS are spectrum disorders induced by drugs with both
      antidopaminergic and serotonergic effects.

PMID- 8748051
TI  - The reflex sympathetic dystrophy syndrome: a review with special reference to
      chronic pain and motor impairments.

PMID- 8748052
TI  - Individualized training reduces excessive exercise hyperventilation in
      asthmatics.

PMID- 8748053
TI  - Acquired hearing loss: social and psychological issues and adjustment processes.

PMID- 8748054
TI  - The effects of age and disability on social support.

PMID- 8748055
TI  - Models of music therapy intervention in stroke rehabilitation.

PMID- 8748056
TI  - The role of the family in disability concerned policies and services: challenges
      for community based rehabilitation in the Asian and pacific decade of disabled
      persons, 1993-2002.

PMID- 8748057
TI  - The present situation of former pupils from schools for the mentally retarded:
      experiences from four countries in western and central Africa.

PMID- 8748058
TI  - Knowledge about and attitudes toward persons with developmental disabilities: an
      assessment of Israeli social work students.

PMID- 8748059
TI  - New insights into panic attacks.

PMID- 8748060
TI  - The effect of elevated systemic cortisol levels on plasma catecholamines in
      Cushing's syndrome patients with and without depressed mood.
AB  - This study explored the effect of elevated systemic cortisol levels on plasma
      epinephrine and norepinephrine, and hemodynamic variables, in patients with
      active Cushing's syndrome; ratings of depressed mood were also obtained.
      Norepinephrine levels were significantly negatively correlated with 24 h urinary
      free cortisol levels. Cushing's patients without depressed mood showed more
      robust negative correlations than those with depressed mood. The inverse
      relationship between norepinephrine and cortisol is consistent with data obtained
      previously in acute studies of normal subjects. Mechanisms which might explain
      these relationships include changes in control of catecholamine production,
      release, and or metabolic clearance in Cushing's patients. The decrease in the
      strength of association in depressed Cushing's patients is consistent with prior
      studies that suggest abnormal relationships between hypothalamic-pituitary
      adrenocortical activity and noradrenergic function in major depressive disorder.

PMID- 8748061
TI  - Patterns of anxiety and personality disorder comorbidity.
AB  - The purpose of this study was to examine patterns of comorbidity of DSM-III-R
      anxiety disorders and personality disorders (PD). Two-hundred subjects were
      independently interviewed with the Structured Clinical Interview for DSM-III-R
      (SCID) and the Personality Disorder Examination (PDE) face-to-face by two
      experienced clinicians. One-hundred and forty-six also completed the Personality
      Diagnositc Questionnaire-Revised (PDQ-R). Rates of personality disorder among
      patients with and without anxiety disorders were determined by each of the three
      instruments. Comorbidity between panic disorder social phobia, obsessive
      compulsive disorder and simple phobia and a conservative estimate of individual
      Axis II disorders was examined. Results indicate that panic disorder, either
      current or lifetime, is associated with borderline, avoidant, and dependent
      personality disorders: social phobia is associated with avoidant personality
      disorder, and obsessive-compulsive disorder is associated with obsessive
      compulsive and avoidant personality disorders. Anxiety disorders with personality
      disorders are characterized by chronicity and lower levels of functioning
      compared with anxiety disorders without personality disorders.

PMID- 8748062
TI  - The familial relationship between panic disorder and unipolar depression.
AB  - This controlled family study explores (1) whether panic disorder and unipolar
      depression share familial factors, and (2) whether the co-occurrence of lifetime
      diagnoses of panic disorder and unipolar depression in individuals defines a
      distinct diagnostic subtype in terms of familial aggregation. To be most
      informative, the familial lifetime prevalence rates for panic disorder and
      unipolar depression have to be determined in a set of four proband groups: 78
      patients with unipolar depression and panic disorder. 121 patients with unipolar
      depression alone (no panic disorder), 81 patients with panic disorder alone (no
      unipolar depression), and 109 control probands sampled in the general population
      were compared by lifetime prevalence rates for panic disorder and unipolar
      depression in their first-degree relatives. Altogether 1046 relatives were
      interviewed directly; family history information was available on another 346
      subjects. Both disorders were aggregating in families. We found modest overlap of
      familial components; the relative risk of panic disorder only in relatives of
      patients with unipolar depression only was 2.3, and the relative risk of unipolar
      depression only in relatives of patients with panic disorder only was 1.8. The
      comorbid condition did not represent a distinct subtype in terms of familial
      aggregation. Excess comorbidity was observed in affected relatives independent of
      the diagnostic status of the index case. Thus, a sharing of familial factors of
      aetiological relevance between panic disorder and unipolar depression might
      explain a limited proportion of comorbid cases. However, the major proportion of
      comorbidity between panic disorder and unipolar depression may still be due to
      non-familial factors.

PMID- 8748063
TI  - Cholecystokinin in psychiatric research: a time for cautious excitement.
AB  - Cholecystokinin (CCK) is a peptide neurotransmitter that was originally isolated
      from the gastrointestinal system, but which is extensively and abundantly
      distributed within the central nervous system (CNS). Stimulated by the fairly
      recent recognition of receptor subtypes (A and B), and the development of
      receptor-specific antagonists, CCK research has been advancing rapidly; and its
      potential importance to psychiatric neuroscience has been increasingly
      recognized. CCK participates in the mediation of satiety; it interacts with
      dopamine and may modulate psychosis; it interacts with opiate systems and may be
      an "anti-analgesic": and it appears to play a role in the mediation of anxiety.
      Highly specific, CCK-B receptor antagonists have reached clinical trials and have
      potential clinical utility as anxiolytics, antipsychotics, anti-anorexics, or
      analgesics. There are grounds for excitement, but many obstacles remain to be
      overcome and clinical potential may not be fulfilled. However, we must not allow
      clinical disappointments to slow the accelerating pace of scientific progress in
      CCK research. Regardless of clinical payoffs, the CCK receptor is clearly of
      great importance to human CNS functioning and deserves ongoing scientific
      attention.

PMID- 8748064
TI  - Cardiac autonomic function during sleep of never-depressed borderline subjects: a
      pilot study.
AB  - In a controlled 48 h ambulatory polysomnographic study of never-depressed
      subjects with DSM-III-R borderline (BDL) personality disorder (PD) we obtained
      measures of tonic and phasic heart rate variability. Subjects with BDL PD showed
      a significantly smaller index of tonic heart rate decrease during NREM sleep than
      normal controls. This is unlikely to be a state-dependent finding and it may
      derive from relative augmentation of adrenergic function compared to cholinergic
      function between wakefulness and NREM sleep. Hyperadrenergic states in BDL PD
      have already been suggested by studies of other biological indicators: a smaller
      index of tonic heart rate decrease may be a further correlate of core
      psychobiological dimensions such as impulsivity and affective instability.

PMID- 8748065
TI  - Circadian patterns of unintended sleep episodes during a constant routine in
      remitted depressed patients.
AB  - Theoretical models of depression have hypothesized phase or amplitude alterations
      in circadian measures including the sleep-wake rhythm. Whether such abnormalities
      occur only during the depressed state, or whether they persist into recovery, is
      less clear. We investigated the circadian pattern of unintended sleep episodes
      during 36 h of constant wakeful bedrest in two groups: 26 drug-free patients
      whose depression remitted following psychotherapy treatment, and a contrast group
      of 17 healthy young adults. The contrast group was not matched for age or gender.
      Both remitted depressed and contrast groups showed statistically significant
      linear and quadratic trends in the number of unintended sleep episodes,
      indicating monotonic and circadian influences across the study interval. We found
      no significant group differences in the pattern of sleep episodes. The number and
      timing of sleep episodes did not correlate significantly with core body
      temperature amplitude or timing or with baseline sleep duration or efficiency.
      The results do not support the hypothesis of a phase or amplitude change in sleep
      propensity as a trait abnormality in depression. However, the inclusion of a
      moderately depressed out-patient cohort, which showed only minor sleep changes
      and normal temperature profiles even while depressed, may have biased against
      finding significant differences.

PMID- 8748066
TI  - Correlates of dissociative symptoms among women with eating disorders.
AB  - We examined the relationship between dissociative symptoms and other Axis I and
      Axis II symptoms among a sample of 53 women diagnosed as having anorexia nervosa
      (n = 18), bulimia nervosa (n = 27), or eating disorder NOS (n = 8). Dissociative
      symptoms were measured by the Dissociative Experiences Scale and the dissociation
      scale from the Trauma Symptom Checklist 40. Severity of dissociative symptoms was
      generally unrelated to severity of bulimic or anorexic symptomatology but was
      significantly associated with severity of anxiety and depression. In terms of
      Axis II symptoms, dissociative symptoms were most highly correlated with
      schizotypal symptomatology (r = .59), uncorrelated with borderline or antisocial
      symptomatology, and slightly negatively correlated with histrionic
      symptomatology.

PMID- 8748067
TI  - Reduced benzodiazepine receptor binding in panic disorders measured by iomazenil
      SPECT.
AB  - We compared a group of nine patients with panic disorder (DSM-III-R) and
      depression with a matched control group of nine dysthymic patients without a
      previous or actual history of panic attacks or anxiety with iomazenil SPECT
      (single photon emission computed tomography) to evaluate panic-related
      abnormalities of the benzodiazepine receptor complex. The panic group had a
      significant decrease (p < .05, U-tests) in the regional activity index (RAI) in
      the following regions after 2 h: lateral inferior temporal lobes, right and left,
      medial inferior temporal lobes, left, inferior frontal lobes, right and left. All
      other regions investigated were not significantly different. The findings may be
      due to either regional blood flow differences or benzodiazepine receptor effects.
      The hypothesis that the effects are due to altered blood flow is confirmed to
      some extent by similar findings in the scans acquired after 10 min. Only the
      hypoactivity in the left lateral temporal region seemed to be independent of
      reduced blood flow in panic disorders.

PMID- 8748068
TI  - Calcium dynamics in the central nervous system.
AB  - Calcium ions are critically important in many functions of the nervous system
      from neurotransmitter release to intracellular signal transduction. The large
      difference between intracellular and extracellular calcium ion concentration
      ([Ca2+]) highlights the importance of the mechanisms controlling influx and
      efflux of this ion. Loss of the regulatory ability of these mechanisms and the
      subsequent increased intracellular calcium levels may be involved in pathological
      events of brain trauma, stroke, epilepsy and other diseases. Ca2+ dynamics in the
      CNS ranging from 'waves' to 'spirals' are being studied because of the
      availability of fluorescent indicators of Ca2+ combined with confocal microscopy.
      Cellular mechanisms of Ca2+ signal transduction have been extensively reviewed
      (Tsien and Tsein, 1990; Carafoli, 1992; Berridge, 1993; Berridge and Dupont,
      1994; Pozzan et al., 1994; Clapham, 1995; Ghosh and Greenberg, 1995). The aim of
      this review is to present the types of Ca2+ dynamics observed in the CNS thus
      far, both in normal brain function as well as in response after injury.

PMID- 8748069
TI  - Multifunctional calcium and calmodulin-dependent kinase II in neuronal function
      and disease.

PMID- 8748070
TI  - Regulation of astrocyte cell biology by the cAMP/protein kinase A signaling
      pathway.

PMID- 8748071
TI  - Calcium uptake by ACTH-stimulated lymphocytes: what is the physiological
      significance?
AB  - Adrenocorticotropic hormone (ACTH) increases cAMP and cGMP concentrations in both
      adrenal and lymphoid cells, and requires extracellular Ca to have biological
      activity. The requirement for Ca has been difficult to characterize in terms of
      the channel identity and whether the committing step for steroidogenesis in the
      adrenal cells requires Ca. In lymphocytes, ACTH has a biphasic effect on
      functions such as proliferation and immunoglobin secretion. Current information
      is consistent with suppressive effects of high ACTH concentrations being mediated
      by cAMP. Stimulatory effects of ACTH concentrations are hypothesized to be
      mediated by Ca uptake. This review will discuss the localization of Ca signals to
      discrete domains within cells and the receptor- and tissue-specificity of their
      subcellular distribution. Considering the diversity of possible mechanisms, a
      hypothesis for the role of ACTH-stimulated Ca uptake during mitogen activation of
      T-cell lymphocytes will be presented.

PMID- 8748072
TI  - The role of adrenoceptor-mediated signals in the modulation of lymphocyte
      function.
AB  - Adrenoceptors are heterotrimeric glycoproteins that bind specific endogenous
      ligands, such as the sympathetic neurotransmitter norepinephrine and the
      neurohormone epinephrine. Ligand binding to an adrenoceptor expressed on the cell
      surface initiates a cascade of biochemical and molecular responses inside the
      cell that lead to a change in cellular activity. Initially, the stimulation of an
      adrenoceptor directly activates G proteins that stimulate enzymes to induce the
      production of second messengers. The cascade continues as the second messengers
      activate serine/threonine protein kinases, resulting in either an inhibition or
      enhancement of cellular activity. The resulting changes in cellular activity are
      mediated by changes in gene expression that are induced by the phosphorylation of
      specific transcription factors. Adrenoceptor subtypes are expressed by both T and
      B lymphocytes. The aim of this review is to summarize and discuss the results
      from the many studies that have examined the role of adrenoceptor-mediated
      intracellular signals in the modulation of lymphocyte function. Another aim of
      this review is to discuss how these studies have advanced our understanding of
      the mechanisms by which the sympathetic nervous system transmits information to
      both T and B lymphocytes to maintain immune homeostasis.

PMID- 8748073
TI  - Morphine stimulates phagocytosis of Mycobacterium tuberculosis by human
      microglial cells: involvement of a G protein-coupled opiate receptor.
AB  - Opiate-induced immunosuppression has been implicated in the pathogenesis of
      infections caused by a variety of microorganisms, including human
      immunodeficiency virus (HIV). Although effects of opiates on lymphocyte function
      have been studied more extensively, morphine also has been shown to inhibit
      several functional activities of mononuclear phagocytes (e.g. chemotaxis,
      respiratory burst activity and phagocytosis). Opiate addiction has been
      identified as a risk factor for clinical tuberculosis prior to the HIV epidemic,
      and macrophages are a key cell in the pathogenesis of Mycobacterium tuberculosis.
      Thus, the hypothesis was tested in the present study that morphine would suppress
      phagocytosis of M. tuberculosis by human microglial cells, the resident
      macrophages of the brain. Contrary to this hypothesis, treatment of human fetal
      microglial cell cultures with morphine (10(-8) M) was found to stimulate
      phagocytosis of nonopsonized M. tuberculosis H37Rv. The stimulatory effect of
      morphine was blocked by naloxone and the mu opiate receptor selective antagonist
      beta-funaltrexamine. Also, morphine-induced increase in phagocytic activity was
      markedly inhibited by pertussis toxin and was unaffected by cholera toxin,
      suggesting the mechanism of morphine's stimulatory effect on microglial cell
      phagocytosis involves a Gi protein-coupled mu opiate receptor. The results of
      this in vitro study support the concept that exogenous and endogenous opioids
      play an immunomodulatory role within the central nervous system through their
      interaction with G protein-coupled receptors on microglial cells.

PMID- 8748074
TI  - Neuroimmunomodulation: classical and non-classical cellular activation.
AB  - As neuroimmunologists, we are often faced with the fact that some substances can
      either enhance or inhibit particular immune/inflammatory cell functions. This
      'duality' could only partially be explained by dose-dependency and the fact that
      in a variety of systems, heterogenous cell populations are commonly used. For
      example it has been repetitively shown that cell proliferation, immunoglobulin
      synthesis and NK (natural killer) activity could be enhanced, inhibited or not
      affected at all by such neuropeptides as somatostatin (SOM) or vasoactive
      intestinal peptide (VIP), depending on the experimental conditions. Even
      substance P (SP), which, in general, stimulates lymphocyte activity, can, under
      certain conditions, possess an inhibitory activity. These apparent discrepancies
      between various groups and experimental conditions met with a strong reservation
      among 'classical' immunologists as they questioned the true physiological role
      that neuro-immune interactions play in normal and disease states. However, upon a
      detailed analysis of the data, it become obvious why such discrepancies abounded.
      Not only are we comparing totally different responses in different species, but
      almost always we compare different experimental conditions. In lieu of this, the
      reproducibility of the experiments within the same laboratory is in fact very
      high. One fundamental and striking observation is the fact that at the level of a
      homogeneous cell population, a differential response could be evoked by the same
      neuropeptide over a range of concentrations. For the purpose of this brief report
      we will focus on the cellular responses to the neuropeptide substance P and we
      will try to illustrate why such differential responses are possible. Some of the
      physiological data relating to the effects of SP on cell function will be
      discussed. This will be followed by a synopsis of SP receptor mechanisms on
      effector cells and finally the mechanism by which SP activates secondary
      messenger systems in these cells.

PMID- 8748075
TI  - Interactions of human immunodeficiency virus type 1 transactivator of
      transcription protein with signal transduction pathways.
AB  - The current state of knowledge investigating Tat interactions with signal
      transduction pathways is still in its infancy but has made significant progress
      toward understanding HIV pathology. This area is of great interest because Tat is
      among a small group of newly discovered RNA-based regulators of transcription.
      What is more important, however, are the implications of understanding these
      interactions concerning HIV-infected individuals. With the failure to develop
      effective HIV vaccines after years of development, it is becoming more feasible
      to conjecture therapies that target Tat as a means to keep HIV in its quiescent
      state rather than to eliminate the virus. In either case, the intense study of
      Tat and signal transduction pathways promises to provide a wealth of information
      about transcriptional control as well as the regulation of immune cell
      activation.

PMID- 8748076
TI  - Subversion of intracellular signal transduction by herpes simplex virus type 1.

PMID- 8748078
TI  - Bilirubin index: a new standard for intervention?
AB  - The current practice for treating neonates for jaundice centers on the
      recommendation that bilirubin levels should be kept below 20 mg/dL. Preventing
      bilirubin levels from exceeding 20 mg/dL, however, does not guarantee the
      avoidance of kernicterus, lower IQs or neurologic abnormalities. Studies in the
      1960s and 1970s reported cases of infants with clinical and pathological
      kernicterus whose neonatal bilirubin levels were well below 20 mg/dL. It is now
      well accepted that protein binding, acidosis, hypoxia, intracranial hemorrhage
      and hemolytic disease play a role in facilitating bilirubin toxicity. This paper
      reviews previously published studies that were instrumental in identifying the
      role of hypoxia, acidosis, hemolytic disease, intracranial hemorrhage and protein
      binding in bilirubin encephalopathy and identifies two key variables which
      contribute to bilirubin flux-free bilirubin concentration and time. The paper
      proposes a new approach for evaluating bilirubin levels termed 'bilirubin index'.
      Future research should initially focus on healthy term infants without
      concomitant illness and should record free bilirubin levels as a function of
      time. The area under the bilirubin versus time curve represents the integration
      of bilirubin level with respect to time, or simply termed the 'bilirubin index'.
      The bilirubin index could then be correlated with parameters for measuring
      neurological outcome. Assuming a correlation would exist, the bilirubin index may
      then become the number for guidance with respect to intervention therapy.
      Attempting to address this issue by starting with a healthy population of
      neonates and correlating bilirubin index with neurological outcome offers a
      better chance for uncovering that 'threshold of toxicity'.

PMID- 8748077
TI  - Role of immune activation and cytokine expression in HIV-1-associated neurologic
      diseases.
AB  - Central nervous system (CNS) involvement is common during human immunodeficiency
      virus type-1 (HIV-1) infection. The neurologic disease of the CNS most frequently
      observed during acquired immunodeficiency syndrome (AIDS) is HIV-1-associated
      cognitive/motor complex or AIDS dementia complex (ADC), which is most likely a
      direct consequence of HIV-1 infection of the CNS. The peripheral nervous system
      (PNS) is also affected in HIV-1-infected individuals and there are several
      features of immune- and cytokine-related pathogenesis in both the CNS and PNS
      that are reviewed. Several lines of evidence demonstrate aspects of immune
      activation in the CNS and peripheral nervous system (PNS) of HIV-1-infected
      individuals. The relative paucity of HIV-1 expression in contrast to widespread
      functional and pathologic changes in the CNS and PNS of AIDS patients, and the
      lack of evidence of productive infection of HIV-1 in neuronal cells in vivo lead
      to the possibility of indirect or immunopathogenic mechanisms for HIV-1-related
      neurologic diseases. Proposed mechanisms of neuronal and glial cell damage are
      injury of oligodendrocytes by tumor necrosis factor-alpha (TNF-alpha) released
      from activated macrophage/microglia, calcium-dependent excitoneurotoxicity
      induced by gp120 HIV-1 envelope protein, N-methyl-D-aspartate (NMDA) receptor
      mediated neurotoxicity by quinolinic acid (a product of activated macrophages),
      cell injury by HIV-1-specific cytotoxic T cells, and apoptosis of
      oligodendrocytes or neurons triggered by interaction between cell surface
      receptors and HIV-1 gp120 protein. Common to those mechanisms is the dependence
      on cellular activation with expression of proinflammatory cytokines (TNF-alpha,
      interleukin-1). Amplification of activation signals through the cytokine network
      by macrophage/astrocyte/endothelial cell interactions, and cell-to-cell contact
      between activated macrophages and neural cells by upregulation of adhesion
      molecules dramatically enhances the toxic effect of macrophage products.
      Expression of immunosuppressive cytokines such as interleukin-4, interleukin-6,
      and transforming growth factor-beta is also increased in the CNS and PNS of HIV-1
      infected patients. This may serve as neuroprotective and regenerative mechanism
      against insults to nervous system tissue.

PMID- 8748079
TI  - Biophysical shunt theory for neuropsychopathology: Part I.
AB  - We present a new model of the origin of schizophrenia based on biophysical ionic
      shunts in neuronal (electrical) pathways. Microstructural and molecular evidence
      is presented for the way in which changes in the neuronal membrane ionic channels
      may facilitate membrane property rearrangement, leading to a change in the
      density and composition of the ion channel charge which in turn causes a change
      in ionic flow orientation and distribution. We suggest that, under abnormal
      conditions, ionic flow shunts are created which redirect the biophysical
      collateral neuronal (electrical) pathways, resulting in psychiatric signs and
      symptoms. This model is complementary to the biological basis of schizophrenia.

PMID- 8748080
TI  - Views on the sustenance of resistant Mycobacterium tuberculosis in the
      environment.
AB  - Microbial resistance to conventional as well as newly introduced drugs is a
      hallmark feature of several infectious diseases, notably tuberculosis. It is
      hypothesized that the greater the selective pressure exerted by increasingly
      potent drugs, the more rapidly is an organism able to adapt to a drug-containing
      environment. The roles of drug-containing environments, and the immunological
      status of the host and bacterial molecular mechanisms of development of drug
      resistance to Mycobacterium tuberculosis have been examined and examples cited
      for implementation of modified drug regimens in tuberculosis-control programmes.
      The views expressed, albeit restricted to Mycobacterium tuberculosis, encourage
      consideration of drug regimens on a disease evolution basis as well as
      understanding of the natural rules that govern development and sustenance of drug
      resistance in the microbial world.

PMID- 8748081
TI  - On some functional roles of the centriole.
AB  - The centriole is conjectured as functioning as an 'autopilot', able to correct
      spindle orientation and polarity in highly deformed cells.

PMID- 8748082
TI  - Anergy, AIDS and tuberculosis.
AB  - Human immunodeficiency virus causes an immunological 'state of anergy'. This
      state is due to a defective function of antigen-presenting cells, a depletion of
      CD4+ helper cells, a reduction in the production of soluble factors required for
      signal transduction, and a decrease in cytotoxic cell activation. The human
      immunodeficiency virus epidemic has resulted in a global resurgence of
      tuberculosis. Tuberculin skin testing is negative in 58% of the patients with
      acquired immunodeficiency syndrome who develop tuberculosis. The mechanism
      leading to a state of anergy and the mechanism leading to dissemination of
      dormant tuberculosis appear to be identical.

PMID- 8748083
TI  - Preovulatory overripeness of the oocyte as a cause of ovarian dysfunction in the
      human female.
AB  - A variety of gynaecological phenomena such as menstrual disorders, infertility
      and premature menopause are associated with ovarian dysfunction. In this paper, a
      factor is considered that may play a role in the aetiology of ovarian
      dysfunction. Animal research has shown that preovulatory overripeness of the
      oocyte may cause various developmental and chromosomal anomalies. Among the
      developmental anomalies observed in amphibia and fish are a number of gonadal
      aberrations, often occurring in otherwise normal specimens. This may be the
      consequence of a degeneration of the 'germinal cytoplasm', cytoplasmic structures
      located in the vegetative pole region of the oocyte, destined to become part of
      future primordial germ cells. Indirect evidence suggests that preovulatory
      overripeness of the oocyte also plays a significant role in human reproductive
      failure. An increased risk of preovulatory overripeness is expected during
      periods of endocrine irregularities, such as the first postmenarcheal years, the
      last premenopausal years, the first months after a pregnancy and, possibly,
      during certain seasons. If the overripeness-induced gonadal maldevelopment
      observed in animals also occurs in humans, this may explain variations in
      reproductive function according to month of birth, as observed in women. It is
      hypothesized that females conceived during periods of maternal endocrine
      irregularities face an increased risk of ovarian dysfunction through overripeness
      induced gonadal maldevelopment.

PMID- 8748084
TI  - The hypothetical epidemic of coronary heart disease and atherosclerosis.
AB  - Accurate usage of the term 'epidemic' is important scientifically and it should
      ideally be used to mean only contagious diseases, not used loosely or emotively
      to mean non-infectious diseases, particularly coronary heart disease, which is a
      non-specific complication of many diseases. It should not be used as a surrogate
      term for atherosclerosis of indefinite severity. An epidemic of atherosclerosis
      is impossible, there being no variation in prevalence because the disease is
      ubiquitous. Moreover, vital statistics are too unreliable to determine the
      existence of an increase or decline in coronary heart disease. A coronary heart
      disease epidemic could be due to an increase in non-atherosclerotic coronary
      heart disease or increased severity of atherosclerosis. The former has not been
      studied and the latter would cause a shift to the left in age distribution and is
      inconsistent with the fall in 'all cause' and stroke mortality rates whilst
      coronary heart disease mortality allegedly increased alarmingly. A coronary heart
      disease epidemic, having no scientific basis, negates any reason for the
      sustained search for a speculative causative environmental factor.

PMID- 8748085
TI  - Melanin, melatonin, melanocyte-stimulating hormone, and the susceptibility to
      autoimmune demyelination: a rationale for light therapy in multiple sclerosis.
AB  - Multiple sclerosis is a central nervous system demyelinating disease. Significant
      evidence, including similarities with its animal model, experimental autoimmune
      encephalomyelitis, supports an autoimmune mechanism, activated by putative
      environmental factors in genetically predisposed individuals. Genetic factors
      strongly influence the susceptibility to demyelinating diseases in humans and
      rodents. Understanding the mechanisms governing susceptibility versus resistance
      may help to identify individuals at risk or design therapeutic strategies. The
      hypothesis formulated here is based on the observation that resistance to
      multiple sclerosis and experimental autoimmune encephalomyelitis is associated
      with dark skin pigmentation. While this may signify a protective role for melanin
      against environmental factors producing oxidative damage, the mechanism
      postulated here is that susceptibility to autoimmune demyelination is influenced
      by hormonal factors, i.e. the neurohormones melatonin and melanocyte stimulating
      hormone, which have opposing effects on immune functions and, the same time, are
      important determinants of the individual's production of melanin.

PMID- 8748086
TI  - Fibrosis causes progressive kidney failure.
AB  - Fibrosis is usually regarded as an uninteresting end-point of injury. However, it
      influences function in heart, lung, and liver. Kidney fibrosis correlates well
      with overall renal function, but is only rarely recognized as affecting function
      itself. There is evidence that organ contraction from fibrotic scarring may
      affect kidney function, and could contribute to progressive renal failure.

PMID- 8748087
TI  - Short note: the potential of umbilical cord blood to increase tissue oxygenation
      in adult respiratory distress syndrome.
AB  - Umbilical blood, consisting mainly of fetal haemoglobin, has an increased oxygen
      affinity. Adult respiratory distress syndrome may be caused by any acute,
      diffuse, infiltrative lung lesion of diverse aetiologies and is characterized by
      severe arterial hypoxia. Mechanical ventilation with high FIO2 and elevated
      pressures is used to improve tissue oxygenation in these patients. Nevertheless,
      adult respiratory distress syndrome may be fatal. Our hypothesis suggests that
      transfusion of umbilical cord blood to adult respiratory distress syndrome
      patients may facilitate oxygen transport by increasing oxygen binding in the
      erythrocytes passing through the damaged lungs. The local hypoxia and the
      accompanied acidosis in the periphery may accelerate the oxygen unload to the
      tissues, thus augmenting overall oxygen delivery. Studies with animals and humans
      show that left-shifted oxyhaemoglobin dissociated curve confers a degree of
      adaptation to low-oxygen tension ambient. Umbilical cord blood is available in
      every hospital, and there are no contraindications to its use.

PMID- 8748088
TI  - An enzymatic effect for cancer prevention and eradication.
AB  - As previously described in a series of hypotheses, cancer development depends on
      an unconvertable duplication mitosis caused by some abnormal supplement of the
      mitotic maturation promoting system which is paralyzed in the cancerous cell's
      cytoplasm. This abnormal supplement, which may be responsible for the cancer's
      development, must be a biochemical compound that could be eliminated by exposure
      to the action of certain enzymes. Accordingly, in order to prevent and eradicate
      cancer development in general, an enzyme which would destroy and eliminate the
      biochemical supplement needs to be identified, and a specific method of
      delivering the enzyme to the supplement needs to be devised.

PMID- 8748089
TI  - Short note: revised schematics for the disentanglement of kinetochore-carrying
      segments.

PMID- 8748090
TI  - Why are vertebrate nervous systems crossed?
AB  - Contralateral central nervous control may be an evolutionary consequence of
      dependence on the image-forming eye, especially in large organisms. As a result
      of the topological transformation of the visual stimulus in the pupillary eye,
      the external environmental hemispace impinges directly upon the contralateral
      internal organismal hemispace. Selective pressure leads to the development of
      central connections capable of the most rapid and precise functional association
      of the internal milieu with the organism's environment. The consequence is
      contralateral central sensorimotor control. Previous hypotheses are discussed,
      including those based on bilaterality, binocularity the optic chiasm and
      avoidance behaviors.

PMID- 8748091
TI  - Tyrosine phosphorylation as a possible regulatory mechanism in the expression of
      human immunodeficiency virus genes.
AB  - Phosphorylation of proteins on serine, threonine and tyrosine is one of the
      significant regulatory mechanisms in gene expression and post-translational
      modifications in both eukaryotes and prokaryotes. Protein tyrosine
      phosphorylation in particular is implicated in cell proliferation,
      differentiation and certain pathological modifications including transformation.
      The overall protein tyrosine phosphorylation is modulated by protein tyrosine
      kinases (PTK) and protein tyrosine phosphatases (PTP). There are several viruses
      known to contain PTK and PTPs. A computer-based protein sequence search using the
      FAST P programme was used to investigate whether, theoretically, a sequence for a
      putative protein tyrosine phosphatase is present in the genomic sequence of the
      human immunodeficiency virus (HIV). A conserved motif GXGXXG characteristic of
      both PTK and PTP was found at the 5' LTR region of the HIV genome. Interesting
      sequence similarities with regulatory proteins of other retroviruses, viz. VPx of
      HIV-2 and X-protein of HTLV-1, and some transforming proteins were also observed.
      The implication of the possible phosphorylation event in association with the HIV
      regulatory proteins tat, rev and nef in AIDS-related malignancies is discussed.

PMID- 8748092
TI  - A genetic hypothesis for cause of death during the 1952 London Fog.
AB  - Analysis of autopsied cause of death during the London Fog of 1952 indicates that
      mortality from all respiratory causes, sudden and delayed, had a consistent male
      fraction of 0.622. Sudden death from heart failure had a similar male fraction of
      0.612. However, heart failures after the first day of illness had a male fraction
      of 0.48. This significant difference in male fraction between sudden (0.61) and
      delayed (0.48) heart failure suggests different terminal events. Coronary sudden
      death may be attributable to right-sided heart failure, and the delayed form may
      be attributable to left-sided failure leading to pulmonary congestion. The male
      fraction in sudden respiratory and sudden cardiac deaths (0.612) is exactly the
      same as the male fraction in sudden infant death syndrome-0.612 - which has been
      posited as being X-linked. It is hypothesized that the same X-linked gene
      responsible for the 0.612 male fraction in sudden infant death syndrome may be a
      factor in the respiratory and sudden cardiac mortalities during the London Fog.

PMID- 8748094
TI  - Opioid involvement in feeding behaviour and the pathogenesis of certain eating
      disorders.
AB  - Incidental findings from animal experiments involving administration of exogenous
      opioid agonists indicate that there are close links between the endogenous opioid
      system and feeding behaviour. Subsequent investigations aimed at elucidating the
      nature of the opioid-feeding relationship led to a wide variety of findings, some
      of them apparently contradictory. This paper examines the effects of opioid
      agonists and antagonists on feeding behaviour, and considers the evidence
      relating levels of endogenous opioids to feeding states, with particular
      reference to certain eating disorders, including anorexia nervosa, bulimia
      nervosa, Prader-Willi syndrome, and eating-induced obesity. The receptors which
      may be involved in opioid-feeding relationships are discussed. Relationships
      between the endogenous opioid system and other systems, such as the dopaminergic,
      noradrenergic and hormonal systems, are considered insofar as they may have
      bearing on the modulation of feeding behaviour. Finally, three theories are
      briefly outlined which attempt to link the endogenous opioid system with feeding
      modulation and the pathogenesis of certain eating disorders. The suggestion is
      put forward that anorexia nervosa may represent a pathological consequence of the
      triggering of a primitive mechanism for coping with unforeseen food shortages
      which may have short-term advantages, e.g., for masking or temporarily
      alleviating a depressed state.

PMID- 8748093
TI  - Mathematical formulae for the prediction of the residual beta cell function
      during the first two years of disease in children and adolescents with insulin
      dependent diabetes mellitus.
AB  - On the basis of a retrospective study of 71 children followed for 24 months after
      diagnosis of type I insulin dependent diabetes a fitted mathematical model was
      constructed for the prediction of the course of beta cell function from the time
      of diagnosis. Two equations were derived, one for the maximal basal (B-max) and
      the other for the maximal i.v. glucagon stimulated peak C-peptide (P-max) levels
      reached during the remission period. The prognostic variables selected for
      analysis were: peak C-peptide levels at diagnosis (Po), age sex, degree of
      obesity, pubertal rating, the presence of islet cell antibodies (ICA) and levels
      of GHb. Multivariate analysis of the data showed that Po (p = 0.0006), puberty (p
      = 0.041). obesity (p = 0.0021), sex (p = 0.031), ICA (p = 0.0045) and GHb(p =
      0.0066) significantly contributed to the prediction formula obtained for B-max
      whereas the contribution of the above variables for P-max were: Po (p = 0.0019),
      puberty (p = 0.0187), obesity (p = 0.0058), sex (p = 0.0598), ICA (p = 0.0187)
      and GHb (p = 0.0027). The residuals of the observed values from the values fitted
      by the predicted equations served to define two separate groups demonstrating
      distinct differences in the natural course of beta cell function in type I
      diabetes. This fitted model may thus be useful in distinguishing between newly
      diagnosed young patients who will undergo remission, requiring lower insulin
      doses, and those who have little chance for remission. It might also be helpful
      in the selection of patients most likely to benefit from immunosuppression or
      modulation, to maximize the benefit to risk ratio for such patients.

PMID- 8748095
TI  - An enzyme/brain-barrier theory of psychiatric pathogenesis: unifying observations
      on phenylketonuria, autism, schizophrenia and postpartum psychosis.

PMID- 8748096
TI  - Diagnostic entropy as a function of therapeutic benefit/risk ratio.
AB  - Current clinical practice is based upon 'out stubborn quest for diagnostic
      certainty' which in turn is considered as one of the major reasons for ever
      increasing health costs. We linked a treatment-threshold concept with classic
      information theory to show that measurable clinical variables, such as benefit
      and risk of available treatments, can be used to calculate the acceptable levels
      of diagnostic uncertainties associated with a particular clinical situation. Our
      analysis shows that practising physicians should aim for diagnostic certainty
      only when the benefit of treatment is equal to its associated risk. In all other
      cases, decisions about treatment do not have to rely on maximum diagnostic
      certainty. Determination of acceptable levels of diagnostic uncertainty according
      to the concepts outlined here should lead to improvement of clinical practice and
      decrease healthcare costs.

PMID- 8748098
TI  - Fraud in science: time for a second look?

PMID- 8748097
TI  - A radical view of gallstone aetiogenesis.
AB  - It is proposed that gallstones stem from insufficiency of micronutrient
      antioxidants relative to the load of oxidants and/or oxidation-prone substrates
      within hepatocytes in such a way that ancillary hepatobiliary resources,
      including bilirubin with lactoferrin and mucin, are mobilized to combat oxidative
      stress but inadvertently promote lithogenesis. Aberrant activities of hepatic
      cytochrome P450 mono-oxygenases and of haem oxygenase are integral to this
      template, because differential inhibition or activation of these enzymes would
      help to rationalize the spectrum of human gallstone composition and also the
      different outcomes when animals are fed the same lithogenic diets. The hypothesis
      is based on a decade of work on another lithogenic disease, chronic pancreatitis.
      It accommodates observations on human and experimental gallstones, it is testable
      and, as shown by studies of chronic pancreatitis, has implications for primary
      disease prevention.

PMID- 8748099
TI  - Consensus, the College and cerebrovascular medicine.

PMID- 8748100
TI  - Guidelines for the use of radioiodine in the management of hyperthyroidism: a
      summary. Prepared by the Radioiodine Audit Subcommittee of the Royal College of
      Physicians Committee on Diabetes and Endocrinology, and the Research Unit of the
      Royal College of Physicians.
AB  - Radioiodine (131I) therapy is indicated in patients with nearly all causes of
      hyperthyroidism. It may safely be given to patients of all age groups but is less
      often given to children under 10 years old. It is completely contraindicated in
      pregnancy and while breast feeding, but there is no increased risk of thyroid
      cancer, leukaemia or solid tumours. Administration of radioiodine must conform to
      regulations and definitions laid down by ARSAC And POPUMET. Medical staff
      authorising therapy must hold an ARSAC licence. The recommended strategy is to
      give an activity sufficient to render the patient rapidly euthyroid and maintain
      that state or achieve no more than a low rate of hypothyroidism in subsequent
      years. A range of activity (300-800 MBq) is suggested depending on the clinical
      state. Antithyroid drugs may be given before or after (or both) radioiodine if
      necessary. Full written information should be given to the patient and written
      consent obtained. A structured follow-up should be used ensuring regular
      measurement of TSH or FT4. Close cooperation with the patient's general
      practitioner is recommended throughout the assessment, treatment and follow-up.
      Shared care with a computer based follow-up system is recommended.

PMID- 8748101
TI  - Alcohol and the young. Summary of a report of a joint working party of the Royal
      College of Physicians and the British Paediatric Association.
AB  - Drinking alcohol is an accepted and pleasurable part of social life. Most adults
      have at least an occasional drink with friends and, apart from those who may
      abstain for religious and other reasons, many would expect alcohol to be provided
      at a family celebration or a party. Yet, as is well known, alcohol in excess can
      kill. As has already been highlighted by four major reports it can affect an
      individual even before birth, and is responsible for significant ill health and
      unhappiness, destroying careers and wrecking family life. Heavy alcohol
      consumption sometimes begins in adolescence. It is therefore important both to
      educate young people about alcohol so that they can take informed decisions and
      to protect young children from its harmful effects.

PMID- 8748102
TI  - Lupus in the Fas lane?
AB  - Fas is a 43 kDa glycoprotein molecule which is involved in inducing apoptosis in
      both B and T lymphocytes. In the murine MRL/Ipr-Ipr model of systemic lupus
      erythematosus (SLE), the lymphoproliferation (lpr) mutation results in defective
      transcription of the gene that codes for the Fas protein. MRL mice which carry
      the homozygous recessive Ipr mutation develop a severe early-onset genetically
      predetermined autoimmune syndrome characterised by high IgG and autoantibody
      levels and a diffuse proliferative immune complex-mediated glomerulonephritis.
      Interest in the importance of Fas in SLE has risen with the observation that 60%
      of human subjects with lupus have elevated levels of the soluble Fas receptor in
      their serum and that the abnormal presence of this molecule may protect
      lymphocytes from undergoing apoptosis. In this review the importance of Fas in
      autoimmune pathogenesis is discussed.

PMID- 8748103
TI  - Acute stroke treatment in UK hospitals: the Stroke Association survey of
      consultant opinion.
AB  - The aim of the Stroke Association survey was to document United Kingdom
      consultant opinion of the immediate treatment for patients with acute stroke. A
      national postal survey of all UK hospital consultant general physicians,
      geriatricians and neurologist was carried out in 1992/3. We identified 1,953
      consultants who routinely cared for patients with acute stroke; 39% of them
      regularly used aspirin for patients with acute stroke and 10% used low-dose
      subcutaneous heparin. Other treatments were rarely used. There was much
      uncertainty about the effectiveness of all currently available acute stroke
      treatments; 73% of physicians were prepared to start aspirin before a CT scan,
      but a much smaller proportion would start heparin therapy without one. Twenty
      seven percent of consultants would actively treat hypertension in the initial 24
      hours after stroke. Routine aspirin for secondary prevention after ischaemic
      stroke was widely accepted, but blood cholesterol lowering by drugs was not. In
      conclusion, aspirin and heparin alone are the only routinely used treatments for
      the immediate treatment of acute stroke; other treatments are used sparingly or
      not at all. The great uncertainty about the value of all available acute stroke
      treatments should encourage participation in randomised controlled trials.

PMID- 8748104
TI  - A prospective study of primary and secondary risk factor management in stroke
      patients.
AB  - Stroke is a common event which often results in death or major loss of
      independence with immense human and financial costs, so identification of
      patients at risk, and prevention of stroke at the individual and population
      levels, is a high clinical and health priority. From August 1993 to July 1994,
      468 stroke patients admitted to our hospital were assessed for the presence of
      stroke risk factors. All patients were followed up in hospital, and on discharge
      or death all hospital records were reviewed. We show that many risk factors
      remain uncorrected in stroke patients and that preventive measures are less than
      ideal at the community and hospital levels alike.

PMID- 8748105
TI  - Wills, living wills and enduring powers of attorney.

PMID- 8748106
TI  - The growth of medical science: the lessons of Malthus.

PMID- 8748107
TI  - Overthrowing the market in health care: the achievements of the early National
      Health Service.

PMID- 8748108
TI  - Do children's rights to health care in the UK ensure their best interests?

PMID- 8748109
TI  - What's in an oath?
AB  - Contrary to popular belief, the Hippocratic Oath (the Oath) is no fixed and
      unalterable document of medical ethics, but has been constantly modified over the
      centuries. Nor was it ever widely sworn or imposed as a condition for obtaining a
      degree or entering practice. The earliest certain evidence for the Oath taken in
      a university comes from 1558, and not until 1804 is there evidence for it being
      sworn by graduands or students. The demand for medical oaths and declarations is
      largely a feature of the second half of the twentieth century, favoured by
      physicians but often viewed with suspicion by patients.

PMID- 8748110
TI  - The toxic effect of language on medicine.

PMID- 8748111
TI  - Therapeutics 1995.
AB  - A joint conference on therapeutics with the Faculty of Pharmaceutical Medicine
      was held at the Royal College of Physicians on 28 June 1995, organised by
      Professor M C L'E Orme. A wide variety of topics was covered ranging from
      management of acute poisoning to the treatment of myocardial infarction, as well
      as the teaching of therapeutics in the new undergraduate medical curriculum. The
      aim of the conference was to provide an overview of the most recent therapeutic
      developments and controversies in the specific subject areas covered.

PMID- 8748112
TI  - Recent advances in rehabilitation medicine.
AB  - Rehabilitation is aimed at minimising the disadvantage experienced by an
      individual as a result of functional impairment or disability following disease.
      It also addresses the impact of the social and environmental consequences of
      disease. Rehabilitation medicine is a new specialty although the concept of
      rehabilitation is not. Previously this work was undertaken within the fields of
      rheumatology, physical medicine, neurology, and orthopaedic, general medical and
      limb fitting services. In some patients, primarily those with neurological and
      musculoskeletal disease, the interaction of impairments with social and
      environmental dimensions can be complex. Effective management requires
      coordination between the patient, carers, and the medical, therapy, nursing,
      psychology and social services. The management of patients with complex
      disabilities is undergoing change with the introduction of new treatments,
      awareness of needs of patients and carers, and new models of care. This
      conference, entitled 'Medical priorities in the rehabilitation of adults with
      complex disabilities' given at the Royal College of Physicians on 2 February
      1995, reviewed these changes. It dealt with medical priorities in rehabilitation
      for patients with specific diseases, and recent advances in areas pertinent to
      rehabilitation medicine.

PMID- 8748113
TI  - Catastrophe and Alzheimer's disease.

PMID- 8748114
TI  - Brain stem death.

PMID- 8748115
TI  - An appropriate admission depends on your viewpoint.

PMID- 8748116
TI  - Why do research ethics committees disagree?

PMID- 8748117
TI  - Effects of dopamine D1 and D2 receptor agonists and antagonists on basal and
      ethanol-modulated beta-endorphin secretion from hypothalamic neurons in primary
      cultures.
AB  - In the present study, we determined the effects of dopamine receptor agonists and
      antagonists on basal and ethanol-modulated beta-endorphin (beta-EP) secretion
      from hypothalamic neurons in primary cultures. Treatment with various
      concentrations of dopamine D1 agonist SKF 38393 and D1 antagonist SCH 23390 did
      not affect basal IR-beta-EP release. However, dopamine D2 receptor agonist LY
      141865 reduced basal immunoreactive (IR)-beta-EP release in a concentration
      dependent manner. D2 receptor antagonist, sulpiride, on the other hand,
      stimulated basal IR-beta-EP release and blocked LY 141865-induced inhibition of
      IR-beta-EP release in a concentration dependent manner. When the actions of these
      DA receptor agents on ethanol-modulated IR-beta-EP release were studied, both D1
      and D2 receptor agents failed to affect ethanol-modulated IR-beta-EP release.
      These data suggest that the endogenous secretion of beta-EP from hypothalamic
      neurons is under the influence of an inhibitory dopaminergic system involving the
      D2 receptor. Furthermore, ethanol's effects on beta-EP secretion are not mediated
      by dopamine.

PMID- 8748118
TI  - Androgen and estrogen effects on vasopressin messenger RNA expression in the
      medial amygdaloid nucleus in male and female rats.
AB  - Vasopressin messenger RNA (AVP mRNA) expression in the medial amygdala and bed
      nucleus of the stria terminalis (BST) is almost completely dependent on gonadal
      steroids. In the BST, the effects of gonadal steroids on AVP mRNA expression are
      sexually dimorphic. Males have more cells that express AVP mRNA and more AVP mRNA
      per cell than females. Here we test whether this is also true for the MA. In
      gonadectomized rats that were treated with testosterone, males had more cells
      that were labeled for AVP mRNA than females. However, the labeling per cell did
      not differ between males and females. To assess contribution of testosterone
      metabolites to these differences, male and female rats were gonadectomized and
      implanted with empty tubing, or tubing filled with dihydrotestosterone (DHT),
      estradiol (E), or E plus DHT (E+DHT). The pattern of steroid effects on AVP mRNA
      expression in the MA was similar in both sexes. Hardly any labeled cells were
      found in rats with empty implants or rats treated with DHT. Significantly more
      labeled cells were found in rats treated with E, and even more cells in rats
      treated with E+DHT. The number of AVP mRNA-labeled cells was higher in males than
      in females for E as well as E+DHT treatment, but the labeling per cell did not
      differ between sexes. These data suggest that the number of MA cells that can
      express AVP mRNA is higher in males than in females, but the estrogen and
      androgen responsiveness of individual AVP mRNA-expressing cells in the MA does
      not differ between sexes.

PMID- 8748119
TI  - Cyclosporin A and FK506 are potent activators of proopiomelanocortin-derived
      peptide secretion without affecting corticotrope glucocorticoid receptor
      function.
AB  - Unliganded glucocorticoid receptors (GR) are localized in the cytoplasm and are
      associated with heat shock protein (hsp)90, hsp70, and a member of the
      immunophilin family, FK506 binding protein 59 (FKBP59). Several members of the
      cyclophilin and FKBP families have now been shown to associate with unactivated
      steroid receptors, however the physiological role these immunophilins play in
      steroid receptor function is questionable. In the present study we have measured
      GR binding and nuclear translocation of activated receptor in corticotrope cells
      following treatment with the immunophilin ligands FK506 and cyclospcrin A (CsA).
      Extensive GR binding studies in AtT20 cells, a mouse corticotrope tumor cell line
      failed to demonstrate an effect of FK506 or CsA on either the ability of GR to
      bind ligand, or on nuclear translocation of the liganded receptor at either a
      saturating or subsaturating dose of dexamethasone (DEX). Consistent with the
      binding data, functionally, neither CsA nor FK506 altered the glucocorticoid
      induced decrease in either proopiomelanocortin (POMC) derived peptide secretion
      or POMC heteronuclear (hn) RNA expression. Despite the fact these drugs did not
      modulate the actions of glucocorticoids on corticotrope cells, both FK506 and CsA
      were potent stimulators of basal beta-endorphin secretion (4-6 fold) from rat
      anterior pituitary cultures and AtT20 cells. In addition, FK506 and CsA
      potentiated beta-endorphin secretion induced by corticotropin releasing factor
      (CRF) and phorbol ester, but had no apparent acute (60 min) effect on POMC hnRNA
      levels. Unlike the acute actions of these immunosuppressant drugs, chronic (24 h)
      treatment lead to a decrease in cytoplasmic POMC mRNA with no apparent change in
      the amount of secreted beta-endorphin. Taken together these data suggest that
      FK506 and CsA do not alter GR activation or function in corticotrope cells,
      however, they are potent but short lived stimulators of POMC-derived peptide
      secretion. The observation that CsA and FK506 stimulate POMC-derived peptide
      secretion, and potentiate both phorbol ester and CRF induced secretion, suggests
      that these immunosuppressant drugs are acting upon a common point within these
      intracellular pathways.

PMID- 8748120
TI  - Long-term antidepressant treatment reduces behavioural deficits in transgenic
      mice with impaired glucocorticoid receptor function.
AB  - Impaired cognitive function and enhanced activity of the hypothalamic-pituitary
      adrenocortical system are among the cardinal symptoms of major depression in
      humans that resolve after successful antidepressant treatment. We used a
      transgenic mouse model expressing antisense RNA complementary to that of
      glucocorticoid receptor (GR) mRNA to test the hypothesis that reduced GR function
      can cause these clinical disturbances. The transgenic mice show profound
      behavioural changes in a number of animal tests that are indicative of cognitive
      impairment. These mice also have elevated plasma corticotropin concentrations in
      response to stress. After long-term treatment with moclobemide, a reversible
      inhibitor of monoamine oxidase type A that acts clinically as an antidepressant,
      both the behavioural deficits and the hormonal alterations disappeared. These
      observations suggest that a transgenic mouse with GR dysfunction may be a useful
      model for investigation of drug effects on the cognitive and neuroendocrine
      aspects of depression.

PMID- 8748121
TI  - Effect of perinatal hypothyroidism on expression of cytochrome c oxidase subunit
      I gene, which is cloned by differential plaque screening from the cerebellum of
      newborn rat.
AB  - Early development of the central nervous system is influenced by several hormones
      including thyroid hormone. This study was designed to clone the gene whose
      expression is changed in association with perinatal hypothyroidism in the rat
      cerebellum. Rats were sacrificed at 15 day-old postnatal age (P15) and their
      cerebella were removed. Poly (A)+ RNA was extracted to construct a cDNA library
      using lambda gt 10 cloning vector. Differential plaque screening was then
      performed using 32P-labeled antisense cDNA synthesized from poly (A)+ RNA of the
      methimazole-treated (hypothyroid) P15 rat cerebellum (hypothyroid probe), and of
      the euthyroid P15 rat cerebellum (euthyroid probe). The clones, which hybridized
      strongly to the euthyroid probe and weakly or not at all to the hypothyroid
      probe, were isolated. Sequence analysis of these clones revealed that all
      isolated clones encode cytochrome c oxidase subunit I (COX I), which is located
      in the mitochondrial DNA. The decrease in COX I gene expression was not seen in
      the animals, which received methimazole treatment and daily replacement of
      thyroid hormone. In situ hybridization detection showed not only overall decrease
      in COX I gene expression but also change in distribution of hybridization signal
      in the cerebellar cortex of hypothyroid rat. Such change was not observed in the
      T4-replaced animals. Based on the evidence that thyroid hormone greatly
      influences brain development, the results of the present study indicate that the
      terminal enzyme of mitochondrial respiratory chain, COX I is one of the important
      target molecules regulated by thyroid hormone in the newborn rat cerebellum.

PMID- 8748122
TI  - Withdrawal of somatostatin augments L-type Ca2+ current in primary cultured rat
      somatotrophs.
AB  - It is known that withdrawal of somatostatin (SRIF) augments the growth hormone
      (GH) releasing hormone (GRF)-induced GH secretion. To investigate the mechanism
      of this augmentation in GH secretion, effects of GRF and SRIF on L-type Ca2+
      current (Ba2+ was used as a charge carrier) or primary cultured rat somatotroph
      were studied by perforated patch clamp technique. The reason is that GRF-induced
      GH secretion is thought to be causally related to the influx of Ca2+ through L
      type Ca2+ channels. 10 mM GRF augmented maximum amplitude of L-type Ba2+ current
      by 12.2% (n = 12). Subsequent application of SRIF slightly suppressed the
      currents but the suppression never exceeded the control level of the current.
      Removal of SRIF, however, promptly augmented the L-type Ba2+ current by 26.8%.
      Such off-response of SRIF was not observed in cells treated overnight with 100
      ng/ml pertussis toxin. Further, specific inhibitor of protein kinase A, H-89 at 1
      microM reversibly suppressed the augmentation of L-type Ba2+ current to control
      level. At 10 microM, H-89 suppressed L-type Ba2+ current by more than 40% from
      control level. These results suggest that (1) L-type Ca2+ channel of somatotroph
      is probably phosphorylated in a basal condition and may be slightly modulated by
      GRF through increased level of cAMP; (2) SRIF only slightly suppress the channel
      activity; (3) Withdrawal of SRIF facilitates the activity of L-type Ca2+ channel
      via PTX-sensitive G-protein, although the precise mechanism of this facilitation
      is unknown. The augmentation by SRIF-pretreatment of GRF-induced GH secretion may
      be at least partly due to the facilitation of the activity of L-type Ca2+
      channel.

PMID- 8748123
TI  - Inhibition of hypothalamic nitric oxide synthase gene expression in the rat
      paraventricular nucleus by food deprivation is independent of serotonin
      depletion.
AB  - We have investigated the effects of food deprivation on nitric oxide synthase
      (NOS) transcript levels in the rat paraventricular (PVN) and supraoptic nuclei
      (SON), using in situ hybridization histochemistry. Food deprivation for 48 h
      significantly and consistently reduced NOS transcript prevalence by approximately
      50% in both sites. Since there is considerable evidence for an important role of
      5-HT in feeding behaviour, we then examined the effect of food deprivation on NOS
      gene expression in the PVN following para-chlorophenylalanine (PCPA)-induced
      hypothalamic 5-HT depletion. As starvation causes central down-regulation of the
      thyroid axis, changes in thyrotropin-releasing hormone (TRH) and pituitary
      thyrotrophin (TSH) transcript prevalence were used as internal controls. PCPA
      pretreatment (200 mg/kg body weight as a single daily dose ip for 2 days) had no
      significant effect on basal levels of NOS, TRH or TSH transcripts, or on the
      effect of a subsequent 48 h fast, which significantly reduced all three. These
      results show for the first time, that food deprivation for 48 h significantly
      reduces NOS gene expression in the rat PVN and SON. Secondly, that basal levels
      and the fasting-induced reductions in the prevalence of NOS, TRH and TSH
      transcripts were not affected by PCPA-induced hypothalamic 5-HT depletion.
      Therefore, at least under the experimental conditions used here, 5-HT does not
      appear to be involved in setting baseline levels- or in the starvation-induced
      inhibition of NOS or thyroid axis gene expression in the PVN.

PMID- 8748124
TI  - Anorexia induced by the parasitic nematode, Nippostrongylus brasiliensis: effects
      on NPY and CRF gene expression in the rat hypothalamus.
AB  - Infections of the gastrointestinal nematode, Nippostrongylus brasiliensis, in the
      laboratory rat result in a characteristic biphasic anorexia which is followed by
      hyperphagia once the worm burden has been cleared. Despite the importance of
      parasite-induced anorexia, relatively little is known of the underlying
      mechanisms. We have investigated the involvement of the central appetite drive in
      this anorexia by studying the gene expression of two neuropeptides with opposing
      actions on energy balance, NPY and CRF. Gene expression was assessed by in situ
      hybridization at 2, 8 and 16 days post-infection (p.i.) in infected rats, in
      uninfected controls, and in a group with food intake restricted to match that
      taken voluntarily by the parasitize animals. The sampling intervals corresponded
      to each of the two phases of maximum anorexia and the period of compensatory
      hyperphagia. Surprisingly, we found that increases in NPY gene expression in the
      hypothalamic arcuate nucleus (ARC) accompany anorexia in rats infected with N.
      brasiliensis; there was a significant relationship between degree of anorexia and
      induction of NPY mRNA after 8 days of infection. Furthermore, ARC NPY mRNA levels
      in parasitized animals were similar to those in pair-fed individuals with food
      intake restricted to match the infected rats. The number of larvae used to
      establish the infection affected both the degree of anorexia and the level of NPY
      mRNA at 8 days p.i. in a dose-dependent manner. NPY gene expression remained
      elevated in infected rats during at least the initial stages of compensatory
      hyperphagia. This suggests that animals detect a state of energy deficit during
      the early stages of the infection, yet do not feed, but become hyperphagic
      coincident with worm loss. The failure of anorectic parasitized animals to feed
      in response to activation of the NPYergic system makes this a novel system in
      which to study the regulation of hypothalamic NPY by physiological challenge.
      There were no significant differences in CRF gene expression between the groups
      at any of the sampling intervals.

PMID- 8748125
TI  - Expression of early genes in estrogen induced phenotypic conversion of
      neuroblastoma cells.
AB  - Estrogens are known to modulate the growth rate and differentiation state of a
      number of cells. In uterine, as well as in mammary tumor cells, estrogen
      dependent proliferation and differentiation are correlated to a series of
      biochemical responses, including increased expression of proto-oncogenes such as:
      c-fos, c-jun and c-myc. Since estrogens were shown to regulate the proliferation
      and the differentiation state of cells of nervous origin, the aim of the present
      study was to investigate whether these effects were associated to changes in the
      expression of early genes. In the model system utilized, the human cell line SK
      ER3, an increase in c-fos mRNA and Fos protein without change of c-jun and
      related genes mRNA concentration was observed after short term treatment with 17
      beta-estradiol (E2). A significant decrease of c-fos, c-jun and jun-D proto
      oncogene mRNA levels were found after prolonged hormonal treatment. The exposure
      to the hormone did not determine any change in N-myc expression. Since the three
      protooncogene mRNAs are rapidly induced following estrogen treatment in other
      cell systems and target tissues, it is concluded that the estrogen-induced
      differentiation of neuroblastoma cells is correlated to a pattern of expression
      of early genes that might be peculiar for the activity of this hormone in neural
      cells.

PMID- 8748127
TI  - The photoperiodic response in Syrian hamster depends upon a melatonin-driven
      circadian rhythm of sensitivity to melatonin.
AB  - The pineal gland, via the daily pattern of melatonin (MEL) secretion, is directly
      involved in the conduction of photoperiodic information. The duration of MEL
      secretion is proportional to the duration of the dark period and, whatever the
      photoperiod is, MEL synthesis occurs 3 or 4 h after the dark onset in Syrian
      hamsters. In order to determine the relative importance of the duration or the
      coincidence hypothesis, a daily infusion protocol was used in sexually active
      pinealectomized hamsters. Long duration of MEL infusion (10 h) completely inhibit
      testes whereas short duration infusion (5 h) had no effect. When the animals were
      infused twice within 2 h 30 min separated by 3 h, they presented a complete
      gonadal atrophy, similar to the one observed with the 10 h infusion. Measurement
      of plasma MEL during the infusion and separation periods revealed that MEL
      reached physiological nighttime values during the infusion period and fell to
      daytime values 1 h after the end of an infusion period. Thus, the results could
      not be due to a time additive action of the two MEL pulses. An intermediate
      response was observed when the 2 signals were applied across the light/dark
      transition. Gonadal regression did not occur when the 2 periods of infusion were
      separated by 5 h 30 min. The efficiency of this type of infusion was not
      dependent on the ambiant photoperiod since similar results were obtained in long
      and short photoperiods. The infusion was also as effective during the day as well
      as during the night. These results suggest that there is a rhythm of sensitivity
      to MEL, based on the coincidence hypotheses, that are important for transmission
      of photoperiodic information. This rhythm of sensitivity to MEL seems to be
      entrained by MEL itself, since the efficiency of the two pulses of MEL is not
      dependent of time of application and/or of photoperiod.

PMID- 8748126
TI  - Intraventricular prolactin inhibits hypothalamic vasoactive-intestinal
      polypeptide-expression in doves.
AB  - While the role of prolactin in promoting the development of the crop-sac in
      members of the pigeon family (Columbiformes) is well established, its action in
      the central nervous system is less well understood. In the present study,
      prolactin was administered intracerebroventricularily (i.c.v.) in ring doves, and
      central expression of vasoactive-intestinal polypeptide (VIP) and gonadotropin
      releasing hormone (GnRH), and the display of sexual behavior was investigated.
      Ovine-prolactin (1 microgram in 2 microliters o-prl) was injected daily for six
      days through chronically implanted cannula either prior to a 2-h period of
      courtship, or late in incubation. Control subjects were given vehicle injections
      and were otherwise identical to experimental animals. Prolactin administered
      prior to courtship resulted in a reduction of sexual behavior, and in a decrease
      in testicular weight but had no detectable effect on the number of neurons
      expressing VIP or GnRH. In contrast, i.c.v. prolactin during incubation resulted
      in a reduced number of infundibular VIP-positive neurons and decreased crop
      weight. We conclude that during incubation prolactin regulates its own synthesis
      and/or release by modulating VIP expression in infundibular neurons.

PMID- 8748128
TI  - The role of transcription factors in the pituitary expression of the glycoprotein
      hormone alpha-subunit gene.

PMID- 8748129
TI  - Prolactin and growth hormone mRNA and protein characterization in SMtTW rat
      pituitary tumours.
AB  - We have combined different techniques to analyse passages of five different rat
      spontaneous pituitary tumours (SMtTW) that were transplanted under the kidney
      capsule. These tumours were secreting prolactin (PRL), GH or both hormones. RIA,
      immunocytochemistry (ICC) and Western blot analysis were applied to characterize
      the hormone(s) stored (ICC and Western blot) and secreted (RIA). mRNA content was
      analysed by PCR, Northern blot analysis and in situ hybridization. The data point
      not only to the reliability of the techniques used at both protein and RNA levels
      for each tumour studied but also to the complementarity of some techniques. For
      example, whereas Northern blot analysis demonstrates the presence and size of
      hormone mRNA, in situ hybridization indicates the percentage of cells expressing
      a given hormone mRNA and allows the presence of one population (or more) of cells
      in a given tumour to be identified. Moreover, the tumours were compared with
      normal rat pituitary. Although the PRL and GH mRNAs were identical in size, the
      amount of mRNA was lower in the tumours. At the protein level, the PRL and GH
      variants exhibited a different pattern of expression in tumours compared with the
      normal rat pituitary. The biological significance of these differences is
      discussed.

PMID- 8748130
TI  - Multiple alternative splice isoforms of parathyroid hormone-related peptide mRNA
      in human cell lines.
AB  - Parathyroid hormone-related peptide (PTHrP) is thought to be responsible for
      hypercalcemia in some patients with malignant tumors. The PTHrP gene has seven
      exons, giving rise to three types of PTHrP isoform through alternative splicing.
      We studied the expression of mRNAs in 14 human cell lines using the reverse
      transcription-PCR method, to examine tissue-specific expression. All the cell
      lines expressed at least two types of PTHrP transcript. Most cell lines expressed
      all four types of PTHrP mRNA isoform. However, a rhabdomyosarcoma cell line, RD,
      and a bladder carcinoma cell line, T24, expressed only two types. These results
      may suggest that PTHrP mRNA is expressed in the majority of tumor and normal
      tissues and that it shows less tissue- or tumor-specificity.

PMID- 8748131
TI  - Expression of IGF-I mRNA in the ovine ovary.
AB  - IGF-I has been implicated as a local and/or systemic regulator of ovarian
      function by acting alone or as an amplifier of the actions of gonadotrophins,
      thereby influencing follicular growth and ovulation. In the sheep it is uncertain
      as to whether IGF-I can fulfil an autocrine or paracrine role, since mRNA
      expression and peptide synthesis have not previously been demonstrated. Using in
      situ hybridization with ovine and human riboprobes, IGF-I mRNA was found in all
      major steroidogenic cell types of the sheep ovary, namely the granulosa, theca
      and luteal cells and, to a lesser extent, the stroma. IGF-I mRNA was found to be
      expressed in the granulosa and thecal cells of early antral follicles and
      thereafter in these cell types as the follicles increased in diameter. Evidence
      for IGF-I mRNA expression in preantral follicles could not be demonstrated. No
      obvious differences in the levels of expression were observed in ovaries
      recovered during the luteal phase, follicular phase, anoestrus or after exogenous
      FSH treatment. IGF-I expression was confirmed by Northern blotting and PCR. These
      findings are consistent with the notion that IGF-I may have an autocrine or
      paracrine role in enhancing ovarian function in the sheep.

PMID- 8748132
TI  - The follicle-stimulating hormone receptor and luteinizing hormone receptor genes
      are closely linked in sheep and deer.
AB  - Restriction fragment length polymorphisms were identified in sheep and deer using
      ovine cDNA probes for the FSH receptor (FSHR) and the LH receptor (LHCGR). FSHR
      and LHCGR were closely linked in sheep with no recombinants and neither receptor
      was linked to the Booroola fecundity gene (FecB). Both receptors were also
      closely linked in deer at a map distance of 3.3 cM. Linkage between the receptor
      genes assigns FSHR to sheep chromosome 3. Sequence analysis showed that the
      mammalian LHCGRs and FSHRs are more similar to each other than to mammalian TSH
      receptor (TSHR). Taken together, these data suggest that TSHR and the LHCGR/FSHR
      arose from a common ancestral gene by a process of chromosomal duplication.
      Subsequent duplication of the region containing the LH/FSH receptor and
      functional divergence could have given rise to the two gonadotrophin receptors
      present in mammals today.

PMID- 8748133
TI  - A thyroid hormone receptor beta gene polymorphism associated with Graves'
      disease.
AB  - Autoimmune thyroid diseases (AITDs) are clustered in families, but the nature of
      this clustering is still poorly understood. One possible approach to the
      identification of genetic factors interacting with the AITDs is the study of the
      association between polymorphic markers and AITDs themselves. In the present
      study we have shown an association between an allele of a HindIII restriction
      fragment length polymorphism (EA beta H) intragenic to c-erbA beta, which codes
      for the thyroid hormone beta receptor, and Graves' disease. This polymorphism can
      be detected by PCR followed by digestion with the restriction enzyme HindIII. The
      allelic frequencies were analysed in a panel of DNAs extracted from a population
      of individuals affected by thyroid disease and originating from southern Italy. A
      control group (n = 120) from the same area was also analysed. The distribution of
      EA beta H alleles was significantly different (P < 0.001) in Graves' disease (n =
      94) but not in autoimmune thyroiditis (n = 60), as compared with controls. Also
      the distribution of the EA beta H genotypes was significantly different in
      Graves' patients (P = 0.003), as compared with controls, the homozygous state EA
      beta H+/EA beta H+ being more frequent in Graves' patients than in all the other
      groups. We did not find any association between EA beta H genotypes and clinical
      parameters in Graves' patients, including eye signs, thyroid volume and level of
      TSH-binding inhibiting immunoglobulins. Our data support the idea that Graves'
      disease is a genetically distinct group within the AITDs.

PMID- 8748134
TI  - FSH receptor gene expression during ovarian follicle development in sheep.
AB  - A key question in elucidating the role of FSH in ovarian function is to determine
      when during follicular growth the FSH receptor first appears. The aim of this
      study was to examine the site and time of FSH receptor gene expression during
      early follicular growth. This study was carried out on ovaries of adult sheep
      during the luteal and prostaglandin-induced follicular phase of the oestrous
      cycle and also on ovaries of fetal sheep at 90, 100, 120 and 135 days of
      gestation (term = day 147). Using reverse transcription-PCR and a set of PCR
      primers spanning exons 8/9/10, two partial FSH receptor cDNAs (500 and 310 bp)
      were isolated from adult sheep ovary. It was shown by sequencing that exon 8 was
      deleted in the 310 bp cDNA, implying that this was part of an alternatively
      spliced FSH receptor transcript. Using RNA in situ hybridisation on ovaries of
      adult sheep, FSH receptor mRNA was observed in granulosa cells of early preantral
      follicles with one to two cell layers and it was seen that gene expression
      continued throughout folliculogenesis into advanced stages of atresia. Moreover,
      in the fetus, FSH receptor gene expression was detected in follicles with two or
      more layers of granulosa cells in ovaries taken at 100, 120 and 135 days of
      gestation. These results suggest that the FSH receptor gene is expressed after
      the granulosa cells of a follicle have begun to divide but not during the
      earliest stages of follicle growth, namely the transformation of a primordial
      follicle to a primary follicle.

PMID- 8748135
TI  - A novel action of epidermal growth factor in rat granulosa cells: its
      potentiation of gonadotrophin action.
AB  - It is well known that epidermal growth factor (EGF) induces down-regulation of LH
      receptors and desensitization to gonadotrophin stimulation in gonadal cells,
      including granulosa cells. In a previous study we showed that EGF receptor levels
      in rat granulosa cells were increased up to fourfold after 96 h of culture with
      human GH in the presence of FSH, and the present study has evaluated the action
      of EGF on these cells. The induced EGF receptors were identical in size to the
      pre-existing receptors as assessed by affinity labelling with 125I-EGF. After 48
      h in culture, various amounts of EGF (0.5-10 ng) were added and the cells were
      cultured for a further 48 h. The addition of EGF caused down-regulation of LH
      receptors in cells expressing high levels of EGF receptors. However, this down
      regulation was less than that in control cells. After the cells were washed, cAMP
      synthesis in response to human chorionic gonadotrophin (hCG) increased by two to
      three times the control value and this increase was closely correlated with an
      increase in EGF receptor content. However, stimulation with cholera toxin or
      forskolin showed no such augmentation, indicating that it may not be due to
      quantitative alterations in G proteins and their effector systems. Induction of
      EGF potentiation required long-term exposure to EGF, for at least more than 24 h.
      In addition, progesterone synthesis was sensitive to stimulation with lower doses
      of hCG. These findings indicate that the activation of hGH-induced EGF receptors
      may potentiate gonadotrophin action in granulosa cells.

PMID- 8748136
TI  - Expression of human insulin-like growth factor-binding protein-3 in transgenic
      mice.
AB  - Transgenic mice which expressed human IGF-binding protein-3 (hIGFBP-3) were
      generated by pronuclear injection of an hIGFBP-3 cDNA driven by the mouse
      metallothionein 1 promoter. Two of the seven founder mice had measurable levels
      of hIGFBP-3 in the circulation. The serum levels of hIGFBP-3 increased as the
      mice were bred to homozygosity and were further induced by supplementing the
      drinking water with 25 mM ZnCl2. While the birth weight, litter size and body
      weight of transgenic mice were not significantly different from non-transgenic
      litter mates or wild-type mice derived from the same genetic background, the
      transgenic mice demonstrated selective organomegaly. The spleen, liver and heart
      of mice derived from both founders were significantly heavier compared with
      organs from non-transgenic mice (P < 0.05, P < 0.005 and P < 0.01 respectively).
      The weights of the brain and kidney were similar in transgenic and non-transgenic
      mice. Expression of the transgene was detected in the kidney, small intestine and
      colon by Northern blot analysis. Western ligand blotting of serum from transgenic
      mice did not demonstrate any change in the abundance of the IGFBPs detected by
      this method. When serum from transgenic mice was incubated with 125I-labeled IGF
      I and analyzed by Sephacryl S-200 chromatography under neutral conditions a
      significantly (P < 0.05) increased amount of the radioactivity was found in the
      140 kDa ternary complex compared with serum from wild-type mice. Immunoreactive
      hIGFBP-3 was detected in the 140 kDa ternary complex but the majority of
      immunoreactive hIGFBP-3 present in transgenic mouse serum eluted in later
      fractions indicating that it was not associated with the acid-labile subunit.
      These data demonstrate that modest constitutive expression of hIGFBP-3 has a
      selective effect on organ growth and development. The establishment of these
      IGFBP-3 transgenic mouse strains may provide useful models to investigate further
      the physiological role of IGFBP-3.

PMID- 8748137
TI  - Structure and sequence of a mouse gene encoding an androgen-regulated protein: a
      new member of the seminal vesicle secretory protein family.
AB  - The gene encoding MSVSP99 (mouse seminal vesicle secretory protein of 99 amino
      acids), an androgen-dependent protein specifically expressed in the mouse seminal
      vesicle, was isolated and sequenced. A mouse genomic library constructed in the
      lambda EMBL12 vector was screened using a full length cDNA probe. One genomic
      clone was selected, 7.4 kb of which were shown to contain the whole MSVSP99 gene.
      The complete sequence of the MSVSP99 gene (1.7 kb), plus 0.8 and 0.3 kb of the 5'
      and 3' flanking regions respectively, has been determined. The gene is composed
      of four exons interrupted by three introns. The size range for the four exons is
      47-217 bp, while that of introns is 87-615 bp. The transcription start site was
      identified as an adenine residue located 21 nucleotides upstream from the ATG
      start codon. Putative TATA and CAAT boxes were identified, along with a number of
      regions that shared homologies with known regulatory sequences. These included
      androgen-responsive elements located in the promoter as well as in the gene
      sequence. Sequence comparisons with other androgen-responsive genes showed strong
      homologies between the MSVSP99 gene and the seminal vesicle secretory protein
      (SVS) family genes (rat SVS II, IV, V and VI). Moreover, some regions were found
      to be conserved between the MSVSP99 gene and the human semenogelin I and II
      genes.

PMID- 8748138
TI  - Introduction--the paradox of inflammation.

PMID- 8748139
TI  - Molecular and cellular interactions mediating granulocyte accumulation in vivo.
AB  - An inflammatory response, either beneficial in host defence or detrimental
      resulting in an inflammatory disease, is associated with alterations in vascular
      tone and blood flow, enhanced vascular permeability to macromolecules and the
      extravasation of leucocytes from the vascular lumen into extravascular tissue.
      The adhesive interaction of granulocytes with venular endothelial cells is an
      essential step in the process of granulocyte accumulation at sites of
      inflammation in vivo. Recent advances made in the field of chemokines and
      adhesion molecules have led to a better understanding of the molecular events
      mediating this important component of the inflammatory response. The defined
      molecular interactions that mediate and regulate these events, in the process of
      neutrophil accumulation, will be discussed in this article. Recently, the
      eosinophil has come into focus because of its prominence in allergic reactions.
      This cell will be discussed in comparison.

PMID- 8748140
TI  - Expression and biology of neutrophil and endothelial cell-derived chemokines.
AB  - The elicitation of polymorphonuclear leukocytes or neutrophils to an area of
      tissue injury is one of the most fundamental of all cell responses during the
      initiation of host defense. Historically, the neutrophil has been identified as
      an important phagocytic cell with a limited capacity to synthesize de-novo
      proteins. However, recent investigations have now shown that stimulated
      neutrophils can express a variety of cytokines, such as tumor necrosis factor,
      interleukin-1, interferon-alpha and interleukin-8. The ability of neutrophils and
      endothelial cells to produce interleukin-8 is extremely important, as this
      chemokine can contribute to the continued maintenance of cell infiltrates into
      the developing inflammatory lesion.

PMID- 8748141
TI  - Granulocyte adhesion molecules--structure/function relationships.
AB  - Neutrophil responses are regulated by cellular adhesion events, including
      interaction with extracellular matrix and other cell types. The diversity of
      molecular structures which are included in the repertoire of cell adhesion
      molecules expressed by neutrophils and their subtle regulation allow fine tuning
      of cell adhesion processes to suit environmental demands. This article reviews
      some of the recent findings using biochemical, immunochemical and molecular
      techniques that allow the relationship between adhesion molecule structure and
      function to be examined. Understanding the molecular basis of cell adhesion
      events will allow development of novel strategies that allow manipulation of
      adhesion processes in a clinical setting.

PMID- 8748142
TI  - Intracellular signaling in neutrophil priming and activation.
AB  - In order for neutrophils to function effectively in host defense, they have
      evolved specific attributes including the ability to migrate to the site of
      inflammation and release an array of toxic products including proteolytic
      enzymes, reactive oxygen species, and cationic proteins. While these compounds
      are intended for killing invading pathogens, if released inappropriately, they
      may also contribute to tissue damage. Such inflammatory tissue injury may be
      important in the pathogenesis of a variety of clinical disorders including
      arthritis, ischemia-reperfusion tissue injury, the systemic inflammatory response
      syndrome (SIRS), and the acute respiratory distress syndrome (ARDS). Despite the
      importance of neutrophil function in host defense and dysfunction in disease
      states, much remains unknown about the intracellular signaling pathways
      regulating neutrophil activity. This review will focus on the signaling molecules
      regulating leukocyte 'effector' functions including receptors, GTP-binding
      proteins, phospholipases, polyphosphoinositide metabolism, and protein kinases
      and phosphatases.

PMID- 8748143
TI  - NADPH oxidase and the respiratory burst.
AB  - Phagocytic cells possess an electron-transport system which accepts electrons
      from NADPH in the cytosol to reduce oxygen to the superoxide radical in the
      vacuolar lumen. The superoxide is instrumental in killing ingested
      microorganisms. Patients suffering from chronic granulomatous disease (CGD), in
      which this system is failing, are abnormally susceptible to infectious diseases.
      Studying CGD patients' neutrophils has been enormously helpful in identifying the
      components of the superoxide-generating system, known as the NADPH oxidase. This
      review will describe the components of the electron-transport chain involved in
      the oxidase and the factors needed for its regulation.

PMID- 8748144
TI  - Neutrophil proteinases and matrix degradation. The cell biology of pericellular
      proteolysis.
AB  - Neutrophil proteinases have the capacity to degrade almost every component of the
      extracellular matrix. In marked contrast to the wealth of available data about
      the structure and activity of these proteinases when they are free in solution,
      there has been relatively little information about the mechanisms by which
      neutrophils use and control their proteolytic enzymes in an extracellular milieu
      that is replete with proteinase inhibitors. However, recent data have provided
      insights into several mechanisms that permit these enzymes to evade inhibition:
      (1) compartmentalization; (2) localized inactivation of proteinase inhibitors;
      (3) tight binding of enzymes to substrates; and (4) binding of proteinases to the
      neutrophil's cell surface.

PMID- 8748145
TI  - Signalling heterogeneity as a contributing factor in macrophage functional
      diversity.
AB  - Macrophages are involved in a variety of different functions in host defence and
      immunity yet they derive from a relatively homogeneous population of precursor
      cells. This article will focus on the mechanisms that contribute to functional
      heterogeneity in monocyte-derived macrophages and how specific stimuli,
      especially cytokines, act alone or in combination to regulate macrophage
      functions in an adaptive fashion. In particular, the thesis will be developed
      that macrophage functional heterogenity may arise as a consequence of
      heterogeneity in transmembrane and intracellular signalling events thereby
      leading to diversity in gene expression.

PMID- 8748146
TI  - Granulocyte clearance by apoptosis in the resolution of inflammation.
AB  - It has recently been recognized that extravasated granulocytes undergo apoptosis
      or programmed cell death. This process controls the functional longevity of these
      cells and is exquisitely modulated by environmental inflammatory mediators. By
      contrast with necrosis, an alternative fate for granulocytes in tissues, during
      apoptosis the granulocyte membrane remains intact and potentially injurious
      granule contents are retained. The intact apoptotic cell is removed by
      macrophages utilizing novel surface recognition mechanisms which fail to trigger
      a pro-inflammatory macrophage response. The balance between granulocyte apoptosis
      and necrosis in inflamed tissues may be an important determinant of the degree of
      tissue injury, and further dissection of the mechanisms of granulocyte apoptosis
      and removal may lead to new therapeutic strategies in inflammatory disease.

PMID- 8748147
TI  - First Cuban symposium on carbohydrates as vaccines, diagnostics and therapeutics.

PMID- 8748148
TI  - Recent progress in the molecular biology of the cloned N
      acetylglucosaminyltransferases.
AB  - Several genes which code for the N-acetylglucosaminyltransferases have been
      cloned and characterized. Physiological and pathophysiological roles of the genes
      still remain to be elucidated but accumulated evidence suggests that the N
      acetylglucosaminyltransferase genes are implicated in differentiation,
      morphogenesis and cancer metastasis.

PMID- 8748149
TI  - Enzymatic transfer of sialic acids modified at C-5 employing four different
      sialyltransferases.
AB  - We present kinetic studies on the enzymatic transfer of several synthetic sialic
      acid analogues, modified at C-5, to distinct glycoprotein glycans by
      sialyltransferases differing in acceptor- and linkage-specificity. Biochemical
      properties of sialic acids were modified by introducing formyl-, trifluoroacetyl
      , benzyloxy-carbonyl-, and aminoacetyl-groups to the amino group at C-5 of
      neuraminic acid. The latter substitution renders the corresponding alpha
      glycoside resistant towards sialidases. The respective CMP-sialic acid analogues
      were prepared by CMP-sialic acid synthase with a yield of 13-55%. The kinetic
      parameters of several sialyltransferases for the 5-substituted CMP-glycosides
      differed significantly. Relative to parent CMP-NeuAc, reaction rates of human-
      and rat liver Gal beta 1, 4GlcNAc alpha 2,6-sialyltransferases ranged from 50 to
      170%, of GalNAc alpha 2,6-sialyltransferases from 40-140%, and of Gal beta 1,3Gal
      NAc alpha 2,3-sialyltransferase from 20-50%. Resialylation of asialo-alpha 1-acid
      glycoprotein by 5-N-formyl- and 5-N-aminoacetyl-neuraminic acid employing rat
      liver Gal beta 1,4GlcNAc alpha 2,6-sialyltransferase proceeded to about 80% of
      galactose sites which is identical to the extent achieved with parent NeuAc.
      According to our data, neosialoglycoconjugates which carry sialic acids modified
      at the N-acetyl group can be prepared for structure-function analysis, as this
      position seems crucial for recognition of adhesion proteins and influenza
      viruses.

PMID- 8748150
TI  - Synthetic substrate analogues for UDP-GlcNAc: Man alpha 1-3R beta 1-2-N
      acetylglucosaminyltransferase I. Substrate specificity and inhibitors for the
      enzyme.
AB  - UDP-GlcNAc:Man alpha 1-3R beta 1-2-N-acetylglucosaminyltransferase I (GlcNAc-T I;
      EC 2.4.1.101) catalyses the conversion of [Man alpha 1-6(Man alpha 1-3)Man alpha
      1-6][Man alpha 1-3]Man beta-O-R to [Man alpha 1-6(Man alpha 1-3)Man alpha 1-6]
      [GlcNAc beta 1-2Man alpha 1-3]Man beta-O-R (R = 1-4GlcNAc beta 1-4GlcNAc- Asn-X)
      and thereby controls the conversion of oligomannose to complex and hybrid
      asparagine-linked glycans (N-glycans). GlcNAc-T I also catalyses the conversion
      of Man alpha 1-6(Man alpha 1-3)Man beta-O-octyl to Man alpha 1-6(GlcNAc beta 1
      2Man alpha 1-3)Man beta-O-octyl. We have therefore tested a series of synthetic
      analogues of Man"alpha 1-6(Man'alpha 1-3)Man beta-O-octyl as substrates and
      inhibitors for rat liver GlcNAc-T I. The 2"-deoxy and the 3"-, 4"- and 6"-O
      methyl derivatives are all good substrates confirming previous observations that
      the hydroxyl groups of the Man"alpha 1-6 residue do not play major roles in the
      binding of substrate to enzyme. In contrasts, all four hydroxyl groups on the
      Man'alpha 1-3 residue are essential since the corresponding deoxy derivatives
      either do not bind (2'- and 3'-deoxy) or bind very poorly (4'- and 6'-deoxy) to
      the enzyme. The 2'- and 3'-O-methyl derivatives also do not bind to the enzyme.
      However, the 4'-O-methyl derivative is a substrate (KM = 2.6 mM) and the 6'-O
      methyl compound is a competitive inhibitor (Ki = 0.76 mM). We have therefore
      synthesized various 4'- and 6'-O-alkyl derivatives, some with reactive groups
      attached to an O-pentyl spacer, and tested these compounds as reversible and
      irreversible inhibitors of GlcNAc-T I. The 6'-O-(5-iodoacetamido-pentyl) compound
      is a specific time dependent inhibitor of the enzyme. Four other 6'-O-alkyl
      compounds showed competitive inhibition while the remaining compounds showed
      little or no binding indicating that the electronic properties of the attached O
      pentyl groups influence binding.

PMID- 8748151
TI  - Large-scale expression of recombinant sialyltransferases and comparison of their
      kinetic properties with native enzymes.
AB  - Values of Km were determined for three purified sialyltransferases and the
      corresponding recombinant enzymes. The enzymes were Gal beta 1-4GlcNAc alpha 2-6
      sialyltransferase and Gal beta 1-3(4)GlcNAc alpha 2-3 sialyltransferase from rat
      liver; these enzymes are responsible for the attachment of sialic acid to N
      linked oligosaccharide chains; and the Gal beta 1-3GalNAc alpha 2-3
      sialyltransferase from porcine submaxillary gland that is responsible for the
      attachment of sialic acid to O-linked glycoproteins and glycolipids. A procedure
      for the large scale expression of active sialyltransferases from recombinant
      baculovirus-infected insect cells is described. For the liver enzymes values of
      Km were determined using rat and human asialo alpha 1 acid glycoprotein and N
      acetyllactosamine as variable substrates; lacto-N-tetraose was also used with the
      Gal beta 1-3(4)GlcNAc alpha 2-3 sialyltransferases. Antifreeze glycoprotein was
      used as the macromolecular acceptor for the porcine enzyme. Values for Km were
      also determined using CMP-NeuAc as the variable substrate.

PMID- 8748152
TI  - Pyridoxal 5'-phosphate binds to a lysine residue in the adenosine 3'-phosphate 5'
      phosphosulfate recognition site of glycolipid sulfotransferase from human renal
      cancer cells.
AB  - In the course of characterization of glycolipid sulfotransferase from human renal
      cancer cells, the manner of inhibition of sulfotransferase activity with
      pyridoxal 5'-phosphate was investigated. Incubation of a partially purified
      sulfotransferase preparation with pyridoxal 5'-phosphate followed by reduction
      with NaBH4 resulted in an irreversible inactivation of the enzyme. When adenosine
      3'-phosphate 5'-phosphosulfate was coincubated with pyridoxal 5'-phosphate, the
      enzyme was protected against this inactivation. Furthermore, pyridoxal 5'
      phosphate was found to behave as a competitive inhibitor with respect to
      adenosine 3'-phosphate 5'-phosphosulfate with a Ki value of 287 microM. These
      results suggest that pyridoxal 5'-phosphate modified a lysine residue in the
      adenosine 3'-phosphate 5'-phosphosulfate-recognizing site of the
      sulfotransferase.

PMID- 8748153
TI  - Regulation of N-acetylglucosaminyltransferase V by protein kinases.
AB  - When 7721 human hepatocarcinoma cells were treated with 100 nM phorbol-12
      myristate-13-acetate (PMA), the activity of N-acetylglucosaminyltransferase V(GnT
      V) in the cells varied in accordance with the activity of membranous protein
      kinase C (PKC), but not with that of cytosolic PKC. Quercetin, a non-specific
      inhibitor of Ser/Thr protein kinase, and D-sphingosine and staurosporine, two
      specific inhibitors of PKC, blocked the activation of membranous PKC and GnT-V by
      PMA. Among the three inhibitors, quercetin was least effective. The inhibitory
      rates of quercetin and staurosporine toward membranous PKC and GnTV were
      proportional to the concentrations of the two inhibitors. The activities of GnTV
      and membranous protein kinase A (PKA) were also induced in parallel by dibutyryl
      cAMP (db-cAMP) and this induction was blocked by a specific PKA inhibitor. When
      cell free preparations of 7721 cells and human kidney were treated with alkaline
      phosphatase (ALP) to remove the phosphate groups, the GnTV activities were
      decreased. These results suggest that GnTV may be activated by membranous PKC or
      PKA, indirectly or directly, via phosphorylation of Ser/Thr residues.

PMID- 8748154
TI  - A soluble form of Sda-beta 1,4-N-acetylgalactosaminyltransferase is released by
      differentiated human colon carcinoma CaCo-2 cells.
AB  - We have previously shown that human colon carcinoma CaCo-2 cells express the Sda
      beta 1,4-N-acetylgalactosaminyltransferase (Sda-beta GalNAc-transferase) and that
      the enzyme activity correlates with the degree of enterocytic differentiation.
      Here we report that a large amount of this glycosyltransferase is released in
      soluble form, particularly when CaCo-2 cells are maintained in culture for more
      than 3 weeks in order to ensure an higher degree of enterocyte differentiation.
      The soluble enzyme was concentrated and partially purified by Blue-Sepharose and
      fetuin-Sepharose chromatography. The substrate specificity of the partially
      purified enzyme was similar to that of Sda-enzyme from epithelial cells of colon
      mucosa, and for its activity strictly required the presence in acceptors of NeuAc
      in alpha 2,3-linkage to subterminal galactose. Among the low molecular glycans
      tested, NeuAc alpha 2,3Gal beta 1,4GlcNAc appeared to be the best acceptor,
      whereas sialyl-Lewisx and sialyl-Lewisa did not serve as acceptors, indicating
      that the fucosylation of sub-terminal GlcNAc hindered the transferase activity.
      Contrary to this, the activity towards a disialylated acceptor such as di-sialyl
      lacto-N-tetraose was reduced but not abolished. When CaCo-2 cells were cultured
      on porous membranes and the transferase activity assayed in medium collected from
      chambers corresponding to either the apical or basolateral face of highly
      differentiated CaCo-2 cells, a preferential release from the basolateral surface
      was found. Considering that Sda-beta GalNAc-transferase is mainly located in the
      large intestine, current results support the notion that colonic cells largely
      contribute to the presence of the enzyme in human plasma.

PMID- 8748155
TI  - Functional purification and characterization of a GDP-fucose: beta-N
      acetylglucosamine (Fuc to Asn linked GlcNAc) alpha 1,3-fucosyltransferase from
      mung beans.
AB  - An alpha 1,3-fucosyltransferase was purified 3000-fold from mung bean seedlings
      by chromatography on DE 52 cellulose and Affigel Blue, by chromatofocusing,
      gelfiltration and affinity chromatography resulting in an apparently homogenous
      protein of about 65 kDa on SDS-PAGE. The enzyme transferred fucose from GDP
      fucose to the Asn-linked N-acetylglucosaminyl residue of an N-glycan, forming an
      alpha 1,3-linkage. The enzyme acted upon N-glycopeptides and related
      oligosaccharides with the glycan structure GlcNAc2Man3 GlcNAc2. Fucose in alpha
      1,6-linkage to the asparagine-linked GlcNAc had no effect on the activity. No
      transfer to N-glycans was observed when the terminal GlcNAc residues were either
      absent or substituted with galactose. N-acetyllactosamine, lacto-N-biose and N
      acetylchito-oligosaccharides did not function as acceptors for the alpha 1,3
      fucosyltransferase. The transferase exhibited maximal activity at pH 7.0 and a
      strict requirement for Mn2+ or Zn2+ ions. The enzyme's activity was moderately
      increased in the presence of Triton X-100. It was not affected by N
      ethylmaleimide.

PMID- 8748156
TI  - Effects of dibutyryl cAMP and bromodeoxyuridine on expression of N
      acetylglucosaminyltransferases III and V in GOTO neuroblastoma cells.
AB  - The sugar chain structures of the cell surface change dramatically during
      cellular differentiation. A human neuroblastoma cell line, GOTO, is known to
      differentiate into neuronal cells and Schwannian cell-like cells on treatments
      with dibutyryl cAMP and bromodeoxyuridine, respectively. We have examined the
      expression of UDP-N-acetylglucosamine: beta-D-mannoside beta-1,4N
      acetylglucosaminyltransferase III (GnT-III: EC 2.4.1.144) and UDP-N
      acetylglucosamine: alpha-6-D-mannoside beta-1,6N-acetylglucosaminyltransferase V
      (GnT-V: EC 2.4.1.155), two major branch forming enzymes in N-glycan synthesis, in
      GOTO cells on two distinct directions of differentiation. In neuronal cell
      differentiation, GnT-III activity showed a slight increase during initial
      treatment with Bt2cAMP for 4 days and decreased drastically after the fourth day,
      but the mRNA level of GnT-III did not show a decrease but in fact a slight
      increase. GnT-V activity increased to approximately two- to three-fold the
      initial level with increasing mRNA level after 8 days, and lectin blot analysis
      showed an increase in reactivity to Datsura stramonium (DSA) of the
      immunoprecipitated neural cell adhesion molecule (NCAM). In Schwannian cell
      differentiation, the activity and mRNA level of GnT-III showed no significant
      change on treatment with BrdU. GnT-V activity also showed no change in spite of
      the gradual increase in the mRNA level. These results suggest that the activation
      of GnT-V during neuronal cell differentiation of GOTO cells might be a specific
      change for branch formation in N-glycans, and this affects the sugar chain
      structures of some glycoproteins such as NCAM.

PMID- 8748157
TI  - A transgenic mouse line with alpha-1,3/4-fucosyl-transferase cDNA: production and
      characteristics.
AB  - cDNA of human alpha-1,3/4-fucosyltransferase (Fuc-TIII) was placed under the
      control of the chicken beta-actin promoter and cytomegalovirus enhancer, then
      introduced into male pronuclei of fertilized mouse eggs. A transgenic mouse line
      thus obtained exhibited enhanced expression of Lex (4C9) antigen in endothelial
      cells located in the glomerulus, sinusoidal capillaries of the liver and
      capillaries of the heart. Furthermore, in the transgenic mice, sialyl dimeric Lex
      (FH6) and sialyl Lea (2D3) antigens were strongly expressed in the glomerular
      endothelial cells.

PMID- 8748158
TI  - Murine monoclonal antibody recognizing human alpha(1,3/1,4)fucosyltransferase.
AB  - We prepared a mouse monoclonal antibody, FTA1-16, that specifically recognizes
      human alpha(1,3/1,4)fucosyltransferase without crossreactivity to any other
      members of the alpha(1,3)fucosyltransferase family. The specificity was confirmed
      by both immunofluorescense staining of native antigens in the Golgi apparatus and
      Western blotting analysis, using stable transformant cells transfected with each
      gene of the alpha(1,3)fucosyltransferase family. Western blotting analysis on a
      series of human tumour cell lines from various tissues revealed that some
      epithelial cancer cell lines from digestive organs expressed an amount of
      alpha(1,3/1,4)fucosyltransferase in good correlation with expression of sialyl
      Lewis a antigen. Immunohistochemical staining by FTA1-16 on colon cancer tissues
      revealed enhanced expression of the enzyme in cancer cells in comparison to
      normal cells. Finally, the antigenic epitope recognized by FTA1-16 was determined
      using truncated recombinant peptides which were expressed in E. coli. A minimal
      length determined was a fragment, amino acid positions 132-153, of the
      alpha(1,3/1,4)fucosyltransferase.

PMID- 8748159
TI  - Preparation of antisera to recombinant, soluble N-acetylglucosaminyltransferase V
      and its visualization in situ.
AB  - N-Acetylglucosaminyltransferase V (GlcNAc-T V) is a glycosyltransferase which
      transfers N-acetylglucosamine in beta(1,6) linkage to the alpha(1,6)-linked
      mannose residue of Asn-linked oligosaccharides. This enzyme is characterized by
      several unusual properties: GlcNAc-T V is the largest lumenal Golgi
      glycosyltransferase described thus far, and its multiple mRNA transcripts range
      from 4.5 to about 9.5 kb; GlcNAc-T V mRNA and activity are regulated by the src
      tyrosine kinase signalling pathway; in brain tissue, large levels of GlcNAc-T V
      mRNA are present, but only relatively low levels of catalytic activity can be
      detected; a lectin-resistant cell line, Lec4A, expresses active GlcNAc-T V which
      is mislocalized intracellularly. In addition, the cell surface oligosaccharide
      products of this enzyme have been hypothesized to regulate intercellular
      adhesion. In order to devise specific inhibitors of this enzyme it is necessary
      to understand its physical structure and how structural changes can influence its
      activity and localization. We have expressed milligram amounts of a soluble form
      of recombinant rat GlcNAc-T V, purified it from CHO cell-conditioned media, and
      used it to prepare specific antisera. This antisera binds selectively to GlcNAc-T
      V and has been used to visualize B-16 mouse melanoma cell GlcNAc-T V on
      immunoblots after SDS-PAGE. When the antisera was used in immunofluorescence
      microscopy experiments on permeabilized B-16 and baby hamster kidney cells,
      intense, specific staining was observed in intracellular structures which appear
      to correspond to the Golgi apparatus.

PMID- 8748160
TI  - Cloning and expression of a porcine UDP-GalNAc: polypeptide N
      acetylgalactosaminyl transferase.
AB  - By employing a bovine UDP-N-acetylgalactosamine: polypeptide N
      acetylgalactosaminyl transferase (O-GalNAc transferase) cDNA as a probe, we
      isolated four overlapping cDNAs from a porcine lung cDNA library. Both the
      nucleotide sequence of the porcine cDNA and the predicted primary structure of
      the protein (559 amino acids) proved to be very similar to those of the bovine
      enzyme (95% and 99% identity, respectively). Transient expression of the clone in
      COS-7 cells, followed by enzymatic activity assays, demonstrated that this cDNA
      sequence encodes a porcine O-GalNAc transferase. The intracellular O-GalNAc
      transferase activity was increased approximately 100-fold by transfecting cells
      with the porcine cDNA.

PMID- 8748161
TI  - CMP-NeuAc:(NeuAc alpha 2-->8)n (colominic acid) sialyltransferase activity in rat
      brain and in tumour cells that express polysialic acid on neural cell adhesion
      molecules.
AB  - A method for the assay of CMP-NeuAc:(NeuAc alpha 2-->8)n (colominic acid)
      sialyltransferase activity was developed. Using a 1-day-old rat brain membrane
      fraction as an enzyme preparation optimal activity was obtained at pH 6.5, 0.3%
      Triton X-100, and 5 mM MnCl2. However, no absolute cation requirement was found
      as EDTA only partially inhibited the activity. Within a concentration range of
      0.3-3 mg colominic acid (which consists of a mixture of oligomers of alpha 2-->8
      linked sialic acid) per 50 microliters a V of 0.61 nmol per mg protein h-1 was
      estimated while a half-maximal reaction velocity was obtained at a concentration
      of 1.75 mg per 50 microliters. High performance anion-exchange chromatography of
      the radioactive products formed in the reaction showed that sialic acid oligomers
      ranging in size from a degree of polymerization (DP) of 2 up to at least DP 9
      could serve as acceptor substrates. Comparison of the acceptor properties of DP 3
      and DP 6 showed that the larger oligomer was acted upon with a 10-fold higher
      efficiency. Periodate oxidation of the products followed by reduction and
      hydrolysis yielded the C7 analogue of NeuAc as the only radioactive product,
      indicating that under the conditions of the assay only a single sialic acid
      residue was introduced into the acceptor molecules. Using the assay it appeared
      that in rat brain the activity of this sialyltransferase decreased six-fold
      during postnatal development to the adult stage. The assay method was also
      applied to lysates of several neuroblastoma and small cell lung tumour cell
      lines, which differ in the expression of polysialic acid as well as of the neural
      cell adhesion molecule NCAM, a major carrier of this polymer. Activity of the
      sialyltransferase appeared to be correlated with the expression of polysialic
      acid present on NCAM. These results indicate that this sialyltransferase might
      function in the process of poly-sialylation.

PMID- 8748162
TI  - Purification, properties, and immunological characterization of GalT-3 (UDP
      galactose: GM2 ganglioside, beta 1-3 galactosyltransferase) from embryonic
      chicken brain.
AB  - A beta 1-3 galactosyltransferase (GalT-3; UDP-Gal; GM2 beta 1-3
      galactosyltransferase) was purified over 5100-fold from 19-day-old embryonic
      chicken brain homogenate employing detergent solubilization, alpha-lactalbumin
      Sepharose, Q-Sepharose, UDP-hexanolamine Sepharose, and GalNAc beta 1-4Gal beta
      Synsorb column chromatography. The purified enzyme was resolved into two bands on
      reducing gels with apparent molecular weights of 62 kDa and 65 kDa, respectively.
      GalT-3 activity was also localized in the same regions by activity gel analysis
      and sucrose-density gradient centrifugation of a detergent-solubilized extract of
      19-day-old embryonic chicken brain. Purified GalT-3 exhibited apparent Kms of 33
      microM, and 14.4 mM with respect to the substrates GM2, UDP-galactose, and MnCl2,
      respectively. Substrate specificity studies with the purified enzyme and a
      variety of glycosphingolipids, glycoproteins, and synthetic substrates revealed
      that the enzyme was highly specific only for the glycosphingolipid acceptors, GM2
      and GgOse3Cer (asialo-GM2). Ovine-asialo-agalacto submaxillary mucin inhibited
      the transfer of galactose to GM2 but did not act as an acceptor in the range of
      concentrations tested. Polyclonal antibodies raised against purified GalT-3
      inhibited GalT-3 activity in vitro and Western-immunoblot analysis of purified
      GalT-3 showed immunopositive bands at 62 and 65 kDa.

PMID- 8748163
TI  - The expression of CMP-NeuAc: Gal beta 1,4GlcNAc alpha 2,6 sialyltransferase [EC
      2.4.99.1] and glycoproteins bearing alpha 2,6-linked sialic acids in human brain
      tumours.
AB  - The expression of CMP-NeuAc: Gal beta 1,4GlcNAc alpha 2,6 sialyltransferase
      (alpha 2,6-ST) [EC 2.4.99.1] and glycoproteins bearing alpha 2,6-linked sialic
      acids were examined in primary human brain tumours and cell lines. 79% (19/24) of
      the meningiomas expressed alpha 2,6-ST mRNA, 42% (10/24) of which showed very
      high expression. alpha 2,6-ST mRNA expression was undetectable in normal brain
      tissue. In contrast, only 1/13 of the gliomas examined expressed detectable alpha
      2,6-ST mRNA. Metastases to the brain did not express measurable amounts of alpha
      2,6-ST mRNA. Less expression was found in malignant (i.e. anaplastic) compared to
      benign (i.e. meningothelial) meningiomas. Two-dimensional SDS-PAGE of glioma and
      meningioma proteins, followed by Sambucus nigra lectin staining, revealed the
      presence of a glycoprotein bearing alpha 2,6-linked sialic acids, M(r) = 53 kDa
      and a pI = 7.0 (MEN-1) that appeared in all seven of the meningiomas examined,
      but was expressed at barely detectable levels, if at all, in seven out of the
      seven glioblastomas examined. Thus, decreased alpha 2,6-ST expression may play a
      role in the aggressive nature of anaplastic meningiomas, but appears to be
      virtually absent in all tumours of glial origin.

PMID- 8748164
TI  - Isolation and characterization of a pseudogene related to human core 2 beta-1,6-N
      acetylglucosaminyl-transferase.
AB  - In a previous study, we isolated genomic clones encoding core 2 beta-1,6-N
      acetylglucosaminyltransferase (C2GnT) and blood group IGnT and proposed that
      these two genes were produced from a common ancestral gene by duplication,
      diversion and intron insertion. In the present study, we have isolated a
      pseudogene which is highly related to the gene of C2GnT. The sequence analysis of
      this pseudogene indicated that the pseudogene was produced by duplication of a
      common precursor gene for C2GnT. These results taken together strongly suggest
      that the ancestral gene was first duplicated and one of the duplicated genes
      directly evolved into the IGnT gene. The other duplicated gene was further
      duplicated to produce the C2GnT gene and the pseudogene.

PMID- 8748165
TI  - Functional domains of bovine beta-1,4 galactosyltransferase.
AB  - A number of N- and C-terminal deletion and point mutants of bovine beta-1,4
      galactosyltransferase (beta-1,4GT) were expressed in E. coli to determine the
      binding regions of the enzyme that interact with N-acetylglucosamine (NAG) and
      UDP-galactose. The N-terminal truncated forms of the enzyme between residues 1
      129, do not show any significant difference in the apparent Kms towards NAG or
      linear oligosaccharide acceptors e.g. for chitobiose and chitotriose, or for the
      nucleotide donor UDP-galactose. Deletion or mutation of Cys 134 results in the
      loss of enzymatic activity, but does not affect the binding properties of the
      protein either to NAG- or UDP-agarose. From these columns the protein can be
      eluted with 15 mM NAG and 50 mM EDTA, like the enzymatically active protein, TL
      GT129, that contains residues 130-402 of bovine beta-1,4GT. Also the N-terminus
      fragment, TL-GT129NAG, that contains residues 130-257 of the beta-1,4GT, binds
      to, and elutes with 15 mM NAG and 50 mM EDTA from the NAG-agarose column as
      efficiently as the enzymatically active TL-GT129. Unlike TL-GT129, the TL
      GT129NAG binds to UDP-columns less efficiently and can be eluted from the column
      with only 15 mM NAG. The C-terminus fragment GT-257UDP, containing residues 258
      402 of beta-1,4GT, binds tightly to both NAG- and UDP-agarose columns. A small
      fraction, 5-10% of the bound protein, can be eluted from the UDP-agarose column
      with 50 mM EDTA alone. The results show that the binding behaviour of N- and C
      terminal fragments of beta-1,4GT towards the NAG- and UDP-agarose columns differ,
      the former binds preferentially to NAG-columns, while the latter binds to UDP
      agarose columns via Mn2+.

PMID- 8748166
TI  - Purification, properties and possible gene assignment of an alpha 1,3
      fucosyltransferase expressed in human liver.
AB  - alpha 1,3-Fucosyltransferase solubilized from human liver has been purified
      40,000-fold to apparent homogeneity by a multistage process involving cation
      exchange chromatography on CM-Sephadex, hydrophobic interaction chromatography on
      Phenyl Sepharose, affinity chromatography on GDP-hexanolamine Sepharose and HPLC
      gel exclusion chromatography. The final step gave a major protein peak that co
      chromatographed with alpha 1,3-fucosyltransferase activity and had a specific
      activity of approximately 5-6 mumol min-1 mg-1 and an M(r) approximately 44,000
      deduced from SDS-PAGE and HPLC analysis. The purified enzyme readily utilized Gal
      beta 1-4GlcNAc, NeuAc alpha 2-3Gal beta 1-4GlcNAc and Fuc alpha 1-2Gal beta 1
      4GlcNAc, with a preference for sialylated and fucosylated Type 2 acceptors. Fuc
      alpha 1-2Gal beta 1-4Glc and the Type 1 compound Gal beta 1-3GlcNAc were very
      poor acceptors and no incorporation was observed with NeuAc alpha 2-6Gal beta 1
      4GlcNAc. A polyclonal antibody raised against the liver preparation reacted with
      the homologous enzyme and also with the blood group Lewis gene-associated alpha
      1,3/1,4-fucosyltransferase purified from the human A431 epidermoid carcinoma cell
      line. No cross reactivity was found with alpha 1,3-fucosyltransferase(s) isolated
      from myeloid cells. Examination by Northern blot analysis of mRNA from normal
      liver and from the HepG2 cell line, together with a comparison of the specificity
      pattern of the purified enzyme with that reported for the enzyme expressed in
      mammalian cells transfected with the Fuc-TVI cDNA, suggests a provisional
      identification of Fuc-TVI as the major alpha 1,3-fucosyltransferase gene
      expressed in human liver.

PMID- 8748167
TI  - Expression of alpha 2,8-sialyltransferase (GD3 synthase) gene in human cancer
      cell lines: high level expression in melanomas and up-regulation in activated T
      lymphocytes.
AB  - GD3 Synthase (alpha 2,8sialyltransferase) (EC 2.4.99.8) cDNA has been cloned by
      eukaryotic cell expression cloning. Using this cDNA as a probe, the expression
      level of the gene in human cancer cell lines was analysed by Northern blotting
      and RT-PCR, then correlated with the ganglioside expression and enzyme activity.
      Melanoma cell lines showed extremely strong bands in Northern blot and RT
      PCR/Southern analysis. The enzyme activity was also very high in melanomas as
      expected. Neuroblastoma and astrocytoma lines showed relatively low levels of the
      gene expression, whereas they expressed high levels of GD2. Although the mRNA
      level of the GD3 synthase gene and enzyme activity in individual cell lines
      correlated positively, some cell lines showed much higher activity than expected
      from the mRNA level. Among leukaemia lines, adult T cell leukaemia-associated
      (HTLV-I+) lines showed fairly high levels of the mRNA. On the other hand, T-ALL
      lines showed very low levels. In addition, GD3 and GD2 expression and mRNA level
      of the gene during T lymphocyte activation were analysed. Only GD3 expression was
      induced by any of the stimulatory reagents used, and corresponding up-regulation
      of the GD3 synthase gene was shown in RT-PCR/Southern analysis.

PMID- 8748168
TI  - Cloning and sequence homology of a rat UDP-GalNAc:polypeptide N
      acetylgalactosaminyltransferase.
AB  - A UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (polypeptide GalNAc
      transferase) cDNA was amplified from rat sublingual, submandibular and parotid
      glands, brain, skeletal muscle, and liver, using the polymerase chain reaction
      (PCR) and sequences derived from bovine polypeptide GalNAc transferase-Type 1
      (polypeptide GalNAc transferase-T1). The transcripts encoding the rat sublingual
      gland and bovine enzymes were 91% identical in nucleotide sequence, except in
      their 5' and 3' untranslated regions. The enzymes encoded by the rat and bovine
      cDNAs were 559 amino acids in length and were virtually identical (98% amino acid
      sequence identity and 99.5% homologous overall). Northern blot analysis indicates
      that the polypeptide GalNAc transferase-T1 transcripts are expressed in many
      tissues but at widely differing levels. Although the amino acid sequence of
      polypeptide GalNAc transferase-T1 is conserved among mammals, the pattern of
      tissue expression varies between rats and humans. For example, the steady-state
      level of polypeptide GalNAc transferase-T1 transcript is quite low in lung
      relative to other rat tissues, whereas high expression of this transcript is
      detected in human lung. Therefore, we surmise that isoforms of polypeptide GalNAc
      transferase must exist and that isoforms are expressed in a tissue-dependent
      fashion. Searches of the GenBank database have revealed homologous sequences for
      several isoforms derived from several human tissues. In addition, hypothetical
      proteins from C. elegans also display strong homology; evidence suggests six
      ancestral isoforms of polypeptide GalNAc transferases may exist in C. elegans.

PMID- 8748169
TI  - Undergraduate training in laboratory animal science: a challenge for change.
AB  - LABORATORY animals are considered to be an 'obscure' specialist area by many
      veterinary surgeons, despite the fact that the knowledge they apply in their
      daily work and all of the medicines they use depend on research or testing using
      laboratory animals. The employment of veterinary surgeons in research is a well
      known aspect of the profession. Less well known is the contribution made by
      veterinarians as toxicological pathologists, assessing the effects of new
      chemicals and pharmaceuticals on laboratory animals used in safety testing. But
      the most important contribution of the profession is as advisers on laboratory
      animal welfare and health. The British Laboratory Animals Veterinary Association
      (BLAVA) is a specialist division of the BVA dedicated to representing and
      educating the profession in this area. Since 1986 every research institute has
      had to employ a named veterinary surgeon to advise on the health and welfare of
      these animals and BLAVA has therefore grown to over 200 members. In this paper
      BLAVA sets out its vision of how undergraduate education could meet this
      challenge.

PMID- 8748170
TI  - Influence of chemoprophylaxis on protective immunity to nematodes in cattle: a
      two-year study comparing four control strategies.
AB  - A two-year study was conducted in three sequential phases. Initially, four
      matched groups of nine calves grazing similar pastures were subjected to
      different chemoprophylactic control programmes while a fifth group acted as
      unprotected controls. After being housed in the autumn, three calves from each
      group and two parasite-naive controls were challenged experimentally with
      Ostertagia ostertagi, Cooperia oncophora and Dictyocaulus viviparus. Post mortem
      worm counts revealed gradations of protective immunity, with the field controls
      showing the highest level and the naive controls the lowest. In the second
      grazing season the remaining animals from each group were grazed together with
      parasitenaive controls on two fields. No further prophylactic treatments were
      given. One of the naive controls developed severe parasitic bronchitis but the
      signs in the other groups were milder and transient. It is concluded that the
      calves protected by chemoprophylaxis in their first grazing season developed
      marked resistance to gastrointestinal and pulmonary nematodes, but that their
      level of immunity was influenced by the effectiveness of the prophylactic
      strategy used.

PMID- 8748171
TI  - Recovery of horses from dysautonomia (grass sickness).
AB  - The outcome for 35 horses with chronic dysautonomia which were kept in the
      hospital at the Royal (Dick) School of Veterinary Studies and subsequently
      returned to their owners is recorded. They constituted 42.7 per cent of the 82
      chronic cases seen between 1991 and 1994; the other 47 horses were euthanased
      while in hospital. Of the 35 animals returned to their owners four died and 27
      were available for follow up; of these 27, 12 were working competitively and six
      were being trained for future competitive work. It takes at least a year before
      it is clear whether a horse can compete successfully again but all the surviving
      animals were capable of being ridden. Some of the horses suffered excessive
      sweating, had difficulty in swallowing some foodstuffs, or had coat changes for
      long periods after returning to a normal weight.

PMID- 8748172
TI  - Effect of captivity on the blood composition of Spanish ibex (Capra pyrenaica
      hispanica).
AB  - Blood analyses of seven free-ranging Spanish ibex (Capra pyrenaica hispanica)
      captured from the wild and then held in captivity were used to determine the
      physiological changes in some haematological parameters and serum chemistry
      values during captivity. The captive animals had a higher haematocrit and
      haemoglobin concentration and larger numbers of erythrocytes than the same
      animals when they were captured. In addition, the absolute numbers of leucocytes
      and lymphocytes decreased progressively during captivity. Significant differences
      were found for some of the biochemical variables between the captive ibex and
      free-ranging animals.

PMID- 8748173
TI  - Suspected annual mercury (Mercurialis annua) poisoning of lambs grazing fallow
      arable land.

PMID- 8748174
TI  - Field diagnosis of nitrite poisoning in cattle by testing aqueous humour samples
      with urine test strips.

PMID- 8748175
TI  - Contagious caprine pleuropneumonia in Uganda and isolation of Mycoplasma
      capricolum subspecies capripneumoniae from goats and sheep.

PMID- 8748176
TI  - Absorption of creatine from meat or other dietary sources by the dog.

PMID- 8748177
TI  - Docking of puppies' tails.

PMID- 8748178
TI  - Protests against live animal exports.

PMID- 8748179
TI  - Rabbit haemorrhagic disease in Ireland.

PMID- 8748180
TI  - Wildlife diseases.

PMID- 8748181
TI  - Magnetic resonance perfusion imaging with gadolinium-DTPA. A quantitative
      approach for the kinetic analysis of first-pass residue curves.
AB  - RATIONALE AND OBJECTIVES: To present a mathematic approach for the analysis of
      first-pass gadolinium (Gd)-DTPA kinetics and to validate the numerical tools
      using simulated and measured kinetics. METHODS: In a capillary plasma filter,
      pulsatile flow was varied between 7.4 and 12.6 mL/second. After contrast bolus
      injection, the arterial input curve and the residue curve were recorded
      simultaneously. Signal intensity versus time curves were converted to
      concentration versus time curves. By deconvolution of these curves and tracer
      kinetic analysis, the mean transit time of the contrast medium through the organ
      model was calculated. RESULTS: A satisfactory correlation (r = 0.98) between the
      inverse of mean transit time and flow measured volumetrically was demonstrated.
      CONCLUSIONS: The kinetic analysis of first-pass curves in an organ model
      indicates that this approach might be useful for in vivo assessment of organ
      blood flow.

PMID- 8748182
TI  - Determination of serum creatinine level before intravenous administration of
      iodinated contrast medium. A survey.
AB  - RATIONALE AND OBJECTIVES: To study the practice of obtaining serum creatinine
      before administering intravenous iodinated contrast medium and the costs
      associated with this practice. MATERIALS AND METHODS: In June 1993, a
      questionnaire was sent to 217 physicians who are members of the Society of
      Uroradiology or the Society of Computed Body Tomography/Magnetic Resonance. There
      were 149 respondents who completed a total of 70 questionnaires, providing a
      response rate of 69% (149/217). RESULTS: The percentage of institutions that
      always require a serum creatinine before administering intravenous contrast
      medium for excretory urography, body computed tomography, and head computed
      tomography was 13%, 20%, and 14%, respectively. In institutions where routine
      serum creatinine is not required, approximately 60% request a serum creatinine in
      either insulin-dependent or juvenile type 1 diabetes. The mean maximal acceptable
      time between the serum creatinine value and contrast administration is 29 days.
      It takes a mean of 69 minutes to get the results of a stat serum creatinine and
      costs a mean of 15 dollars for the test. In patients with no risk factors, the
      mean for the highest serum creatinine value at which respondents still gave
      contrast was 2.1 mg/dL; in patients with risk factors, the mean was 1.9 mg/dL.
      There was no correlation between the use of serum creatinine and the number of
      studies performed in the institution or the type of contrast used. CONCLUSIONS:
      The practice of requiring a pretest serum creatinine and its interpretation
      regarding the use of contrast media are quite variable. In view of this disparity
      in opinion, development and acceptance of a list of patients who are at increased
      risk for contrast-induced nephropathy may be desirable.

PMID- 8748183
TI  - Characterization of reactive versus tumor-bearing lymph nodes with interstitial
      magnetic resonance lymphography in an animal model.
AB  - RATIONALE AND OBJECTIVES: To determine if magnetic resonance lymphography
      performed with subcutaneously administered AMI-227, a nanoparticulate iron oxide
      contrast agent, can distinguish reactive from tumor-bearing lymph nodes.
      MATERIALS AND METHODS: Mature male Copenhagen rats were inoculated with cell
      suspensions of R3327-MAT-LyLu rat prostate carcinoma (n = 21) or Freund's
      complete adjuvant (n = 15) in the left footpad to generate ipsilateral popliteal
      lymph node metastases or lymphadenitis. At 12 to 14 days after inoculation, T1
      and T2-weighted magnetic resonance images of bilateral popliteal areas were
      obtained before and 24 hours after subcutaneous administration of AMI-227.
      Contrast-to-noise ratios were calculated in precontrast and postcontrast images.
      Bilateral popliteal nodes were excised for pathologic assessment. RESULTS: AMI
      227 resulted in decreased contrast-to-noise ratios in reactive (T1-W = -7.01 +/-
      1.13, T2- W = -31.64 +/- 5.35) and normal (T1 - W = -13.56 +/- 1.97, T2 - W = 
      21.62 +/- 2.51) nodes. Contrast-to-noise ratios were unchanged (T1 - W = -0.22 +/
      1.71, T2 - W = -2.20 +/- 4.19) in tumor-containing nodes. These differences in
      contrast-to-noise ratio changes between tumor-bearing versus nontumor-bearing
      nodes were statistically significant (P < 0.05). Histologic analysis showed
      similar distribution of AMI-227 within normal and reactive nodes, but not in
      tumor-bearing nodes. CONCLUSIONS: Differences in AMI-227-uptake between tumor-
      and nontumor-bearing nodes detected with magnetic resonance imaging are helpful
      for distinguishing the two entities.

PMID- 8748184
TI  - Value of computed tomography in patients with persistent vertigo after stapes
      surgery.
AB  - RATIONALE AND OBJECTIVES: The value of computed tomography was evaluated in 14
      patients with persistent vertigo after otosclerosis operation. METHODS: High
      resolution computed tomography was performed with 1-mm slice thickness and table
      feed in the axial and coronal planes. RESULTS: Computed tomography scans showed
      in 13 case findings that related to symptoms. An air bubble at the end of the
      prosthesis as a new, indirect sign of a perilymphatic fistula was found in 6
      cases. An incorrect position of the stapes prostheses was diagnosed in 7
      patients. One patient had recurrence of otosclerosis, and two others developed
      scarring around the prosthesis. In 1 case, an incus necrosis was found. Some
      patients showed two signs simultaneously. The computed tomography results were
      confirmed by retympanotomy in 12 cases. CONCLUSIONS: Computed tomography proved
      to be a valuable method in the diagnosis of persistent vertigo after otosclerosis
      operation. The indication for a repeat operation was facilitated by the use of
      computed tomography.

PMID- 8748185
TI  - Renal pathology after arterial yttrium-90 microsphere administration in pigs. A
      model for superselective radioembolization therapy.
AB  - RATIONALE AND OBJECTIVES: To test the selectivity of tissue damage in
      radioembolization, the authors performed an experimental study using
      superselective administration of yttrium-90 particles to deliver up to 100 Gy to
      the porcine kidney. Patterns and severity of damage in test organs were compared
      with controls, and the feasibility of this model is discussed. METHODS: Eight
      sows were included in the study. Bio-Rex 70 particles were applied via selective
      catheterization of the renal artery. Four pigs received inactive particles and
      four pigs received active particles. Organ distribution and shunting of yttrium
      90 were determined, and kidney damage patterns were histologically analyzed.
      RESULTS AND CONCLUSIONS: The model demonstrates that yttrium-90-labeled resin
      particles can superselectively be applied. Retention of beta activity in the
      target organ was more than 95%. In addition to tissue shrinkage from mechanical
      obstruction, considerable damage ensued mainly by radiation-induced arterial
      necrosis and arteritis.

PMID- 8748186
TI  - Squamous cell carcinoma of the uterine cervix. Patterns of thoracic metastases.
AB  - RATIONALE AND OBJECTIVES: Distant metastasis of cervical cancer, once considered
      rather uncommon, has become more common in recent years because of longer
      survival of the patients. The purpose of this study is to evaluate the
      radiographic patterns of its thoracic metastases correlating with the pathways of
      metastatic tumor spread. METHODS: The conventional radiographs (62 cases),
      thoracic computed tomography images (20 cases), and medical records of 62
      patients with advanced squamous cell carcinoma of the uterine cervix with
      thoracic metastases who died of extensive disease and its complications during a
      recent 5-year period were reviewed retrospectively. RESULTS AND CONCLUSIONS: In
      addition to the most typical pattern of multiple pulmonary nodules (71%),
      mediastinal and hilar lymphadenopathy (32%) and pleural metastases (27%) were
      frequently observed. Rare findings included bone metastases (6%), endobronchial
      obstruction (5%), and lymphangitic carcinomatosis (3%). The mechanisms of
      metastasis in relation to the above manifestations are proposed.

PMID- 8748187
TI  - Optimization of a breath-hold magnetic resonance gradient echo technique for the
      detection of interstitial lung disease.
AB  - RATIONALE AND OBJECTIVES: A rapid gradient echo technique was optimized to allow
      breath-held imaging of the lung parenchyma. The ability of this sequence to
      detect interstitial lung disease was then compared with high resolution computed
      tomography. METHODS: A Turbo-FLASH gradient echo sequence (repetition time [TR]
      4.7, echo time [TE]2) was optimized using four volunteers. The parameters varied,
      including flip angle, inversion time, slice thickness, and number of measurements
      per unit time. The effect on signal to noise ratio of lung inflation and position
      within the lung were also studied. The optimized sequence was then compared with
      high resolution computed tomography in five patients being investigated for
      interstitial lung disease. RESULTS: Greatest signal was achieved using no
      inversion prepulse. This allowed up to six measurements, each with two
      acquisitions, during a single breath-hold. Optimum signal to noise ratio was
      achieved using a flip angle of 10 degrees with a 20-mm slice thickness, although
      a 10-mm slice was felt to be preferable for clinical use. Greatest signal to
      noise ratio was generated in the posterior aspect of the lung in full expiration.
      Comparison of the optimized magnetic resonance imaging technique with high
      resolution computed tomography showed no significant difference (P = 0.17) when
      assessing the proportion of diseased to normal lung. CONCLUSIONS: Using standard
      magnetic resonance software and hardware, it has been possible to use a breath
      hold sequence that allows detection and quantification of interstitial lung
      disease.

PMID- 8748188
TI  - Hydrogen magnetic resonance spectroscopy follow-up after radiation therapy of
      human brain cancer. Unexpected inverse correlation between the changes in tumor
      choline level and post-gadolinium magnetic resonance imaging contrast.
AB  - RATIONALE AND OBJECTIVES: The anatomic and metabolic changes in human brain
      tumors treated by radiation therapy were compared using gadolinium-enhanced
      magnetic resonance imaging and hydrogen (1H) magnetic resonance spectroscopy. The
      study was intended to assess the potential of 1H magnetic resonance spectroscopy
      in monitoring response to therapy. METHODS: Thirteen cases of brain cancer
      treated by radiation therapy were examined by 1H magnetic resonance spectroscopy
      and gadolinium-enhanced T1-weighted magnetic resonance imaging and reexamined at
      2-month intervals. RESULTS: Follow-up after radiation therapy showed changes in
      post-gadolinium magnetic resonance imaging contrast that are inversely correlated
      with the changes in choline level (r = -0.69, P < 0.00001) and in tumor volume (r
      = -0.35, P < 0.05). CONCLUSIONS: The choline loss in tumors gaining post
      gadolinium magnetic resonance imaging contrast after therapy is unexpected in
      view of previously reported correlation between the two in untreated metastatic
      brain tumors. Indicated is the use of 1H magnetic resonance spectroscopy to
      discriminate enhancing brain tumors with a high content of vital tumor cells
      (high choline) from tumors, combining decreased cell density with increased
      interstitial space (low choline).

PMID- 8748189
TI  - Cardiac and hemodynamic tolerability of iodinated contrast media in the
      anesthetized rat.
AB  - RATIONALE AND OBJECTIVES: The study was designed to compare the hemodynamic
      effects of 11 iodinated contrast media (CM), including ionic (diatrizoate,
      ioxaglate), nonionic monomeric (iohexol, iopromide, iopamidol, iopentol,
      ioversol, iomeprol, ZK 139129), and nonionic dimeric (iotrolan, iodixanol)
      compounds. METHODS: Following left ventricular bolus injection of 1.2 g I/kg body
      weight in anesthetized rats, cardiohemodynamic parameters were measured. RESULTS:
      Compared with the control group, except for blood pressure (BP), all CM showed a
      similar response regarding the direction of the cardiohemodynamic changes after
      CM injection. A biphasic change in BP was observed for diatrizoate and iodixanol,
      whereas all other CM showed a transient increase in BP being most pronounced for
      ioxaglate. No arrhythmias were detected. The increase in LVEDP was lowest for the
      isotonic dimeric CM iotrolan and iodixanol. CONCLUSIONS: Only mild transient side
      effects were observed. Low osmolar, especially isotonic, dimeric CM show a clear
      benefit regarding cardiovascular side effects.

PMID- 8748190
TI  - Optimal calcium intake. Sponsored by National Institutes of Health Continuing
      Medical Education.
AB  - The National Institutes of Health Consensus Development Conference on Optimal
      Calcium Intake brought together experts from many different fields including
      osteoporosis and bone and dental health, nursing, dietetics, epidemiology,
      endocrinology, gastroenterology, nephrology, rheumatology, oncology,
      hypertension, nutrition and public education, and biostatistics, as well as the
      public, to address the following questions: 1) What is the optimal amount of
      calcium intake? 2) What are the important cofactors for achieving optimal calcium
      intake? 3) What are the risks associated with increased levels of calcium intake?
      4) What are the best ways to attain optimal calcium intake? 5) What public health
      strategies are available and needed to implement optimal calcium intake
      recommendations? and 6) What are the recommendations for future research on
      calcium intake? The consensus panel concluded that: A large percentage of
      Americans fail to meet currently recommended guidelines for optimal calcium
      intake. On the basis of the most current information available, optimal calcium
      intake is estimated to be 400 mg/day (birth-6 months) to 600 mg/day (6-12 months)
      in infants; 800 mg/day in young children (1-5 years) and 800-1,200 mg/day for
      older children (6-10 years); 1,200-1,500 mg/day for adolescents and young adults
      (11-24 years); 1,000 mg/day for women between 25 and 50 years; 1,200-1,500 mg/day
      for pregnant or lactating women; and 1,000 mg/day for postmenopausal women on
      estrogen replacement therapy and 1,500 mg/day for postmenopausal women not on
      estrogen therapy. Recommended daily intake for men is 1,000 mg/day (25-65 years).
      For all women and men over 65, daily intake is recommended to be 1,500 mg/day,
      although further research is needed for this age group. These guidelines are
      based on calcium from the diet plus any calcium taken in supplemental form.
      Adequate vitamin D is essential for optimal calcium absorption. Dietary
      constituents, hormones, drugs, age, and genetic factors influence the amount of
      calcium required for optimal skeletal health. Calcium intake, up to a total
      intake of 2,000 mg/day, appears to be safe in most individuals. The preferred
      source of calcium is through calcium-rich foods such as dairy products. Calcium
      fortified foods and calcium supplements are other means by which optimal calcium
      intake can be reached in those who cannot meet this need by ingesting
      conventional foods. A unified public health strategy is needed to ensure optimal
      calcium intake in the American population.

PMID- 8748191
TI  - Medium-chain triglycerides for parenteral nutrition: kinetic profile in humans.
AB  - Medium-chain triglycerides (MCTs) have been introduced as lipid substrates in
      parenteral nutrition because of their rapid and complete oxidation. Although
      there are many clinical studies on the use of MCTs in parenteral nutrition there
      are only a few studies on their kinetics; most of these studies used indirect
      methods (such as light scattering) to determine MCT concentrations in plasma. We
      determined the hydrolysis rate of MCTs to medium-chain fatty acids (MCFAs) and
      the disposition rate of MCFAs in nine healthy volunteers who received an
      intravenous bolus of MCTs as 10% MCT + 10% long-chain triglyceride solution. MCTs
      and MCFAs were analyzed by gas-liquid chromatography. One linear compartment
      model was used and its parameters were numerically estimated. The first-order
      transformation constant of the hydrolysis step from MCT to MCFA was 0.0964 +/-
      0.0152 min-1(for 8- and 10-carbon pooled together); the rate constant for tissue
      MCFA uptake from plasma was 0.0725 +/- 0.0230 min-1. The apparent volumes of
      distribution were about 4.5 L for MCT and 19 L for MCFA in a typical 70-kg
      subject. The plasma half-life of MCT was 11 min and that of MCFA was 17 min. The
      limiting step in the clinical use of MCTs seems to be tissue uptake of MCFAs.

PMID- 8748192
TI  - Differential effects of counterregulatory stress hormones on serum albumin
      concentrations and protein catabolism in healthy volunteers.
AB  - Postoperative hypoalbuminemia occurs frequently; however, the cause of this
      disorder is not clear. In a double-blind, placebo-controlled study we
      investigated to what extent hypoalbuminemia and protein catabolism are caused by
      counterregulatory stress hormones, which play an important role in the metabolic
      changes that follow surgery. We simulated the postoperative endocrine response in
      healthy volunteers with a cocktail of the counterregulatory hormones epinephrine,
      glucagon, and hydrocortisone. Saline was infused as a control in a second
      experiment. Serum albumin and stress hormone concentrations and nitrogen balance
      were measured for 34 h and were compared with published values for patients after
      abdominal surgery. Triple-hormone infusion mimicked the endocrine response after
      abdominal surgery adequately. It caused a negative nitrogen balance comparable
      with that after moderately severe surgery but no hypoalbuminemia (serum albumin <
      35 g/L), although serum albumin was slightly reduced relative to the control
      group. No net nitrogen loss or hypoalbuminemia occurred after saline infusion. In
      conclusion, counterregulatory stress hormones do not cause hypoalbuminemia in
      healthy volunteers, but do produce protein catabolism.

PMID- 8748193
TI  - Effect of passive stretching on the wasting of muscle in the critically ill.
AB  - This study examine whether muscle wasting in critically ill patients can be
      prevented by passive stretching alone in the absence of contractile activity.
      Five critically ill patients who required a complete neuromuscular blockade for 7
      days of ventilator support were studied. One leg of each patient was treated with
      continuous passive motion (CPM) for three 3-h periods daily while the other leg
      received only routine nursing care. Fiber atrophy was prevented in the more
      severely ill patients and there was a slight gain in fiber area (mean increase,
      +11%) in the CPM limb compared with the control leg, which decreased (mean
      decrease, -35%) over 7 days. Fiber area was preserved in both fiber types but was
      more pronounced in type I muscle fibers. Protein loss was significantly less in
      the CPM limb. There was a significantly greater increase in wet weight per mg DNA
      in the control limb. However, as an index of wasting, the ratio of protein to DNA
      decreased similarly in both limbs. Passive stretching can preserve the
      architecture of muscle fibers. Whether it can prevent muscle wasting remains
      uncertain.

PMID- 8748194
TI  - Biochemical indices may not accurately reflect changes in nutritional status
      after allogeneic bone marrow transplantation.
AB  - The validity of biochemical indices routinely used for nutritional assessment was
      evaluated in patients undergoing allogeneic bone marrow transplantation for
      hematologic malignancies. Sixteen patients received total parenteral nutrition
      (TPN) for 15 days (35 kcal kg.body wt-1.day-1; 1.4 g amino acid.kg body wt-1.day
      1) starting 1 day after transplantation. Nutritional status was evaluated before
      and after the TPN period by determining anthropometric (body weight, triceps
      skinfold thickness, and midarm circumference) and biochemical (transferrin,
      prealbumin, ceruloplasmin, and C3c) indices. Anthropometric indices, which were
      within the normal range before TPN, were not changed on day 15; transferrin and
      prealbumin concentrations significantly (p = 0.03) decreased whereas
      ceruloplasmin and C3c significantly (p = 0.03) increased. The levels of acute
      phase proteins (alpha-1-acid glycoprotein, alpha-1-antitrypsin, and C-reactive
      protein), determined in 8 of the 16 patients at the same time intervals, were
      increased after 15 days of TPN and were significantly inversely correlated with
      transferrin and prealbumin. On the basis of these data, it appears that
      biochemical indices are not sufficiently reliable in the nutritional assessment
      of bone marrow transplantation patients because the levels of these substances
      are markedly affected by the acute-phase response secondary to febrile episodes
      and graft-versus-host disease, which frequently complicate transplantation.

PMID- 8748196
TI  - Time course of changes in rat serum lecithin-cholesterol acyl-transferase
      activity and high-density-lipoprotein composition during the consumption of two
      different low-protein diets followed by a balanced diet.
AB  - We studied the effects of low-protein diets on high-density-lipoprotein (HDL)
      composition and checked whether the changes observed were correlated with
      lecithin-cholesterol acyl-transferase (LCAT) activity. We also studied whether
      HDL lipid and protein compositions and LCAT activity were modified differently in
      growing rats during the consumption of two low-protein diets [2% casein (C) and
      5% gluten (GI)] for 28 days, followed by the refeeding of a balanced diet
      containing 15% casein for 14 days. The control group was fed the balanced diet
      for 42 days. LCAT activity was determined by conversion of 3H-cholesterol into 3H
      esterified cholesterol. The consumption of both protein-depleted diets highly
      decreased LCAT activity. At the end of the period of protein malnutrition, LCAT
      activity was only 22% and 13% of that of the control group in the C and GI
      groups, respectively. There was no significant difference between the two
      depleted diets. At day 3 of refeeding, values of both C and GI groups returned to
      control values. Despite the reduction in LCAT activity with both types of protein
      depleted diets, HDL metabolism was not significantly impaired. This might be
      partly due to the maintenance of higher apolipoprotein A-I levels. The reduced
      LCAT activity could be attributable to reduced synthesis of LCAT in the liver
      during both protein-depleted diets.

PMID- 8748195
TI  - Dietary fatty acid modulates actions of nucleotides on humoral immune responses.
AB  - Polynucleotides enhance T cell-dependent antibody production in culture. Impaired
      antibody production in mice fed a nucleotide-free diet can be easily restored by
      in vivo supplementation of both a mononucleotide-nucleoside mixture (OG-VI) and
      polynucleotides. Polynucleotides appear to act partly by modulating antigen
      presentation processes mediated by cell surface molecules. We examined whether
      dietary fatty acid manipulation alters nucleotides' actions on humoral immunity.
      Antibody production was studied in C57B1/6 mice fed I) a nucleotide-free diet
      high in saturated fatty acid (SFA diet), 2) a nucleotide-free diet high in
      polyunsaturated fatty acid (PUFA diet), and 3) a regular nucleotide-free diet
      (control). In vivo and in vitro T cell-dependent antibody production decreased in
      all groups, but mice fed the SFA diet produced more antibody in vivo than did
      mice in the other diet groups. Spleen cells from mice fed the SFA diet also
      produced more interferon-alpha when stimulated with mitogens than did those from
      mice fed the control diet. In contrast, polynucleotides enhanced in vitro
      antibody production much less efficiently in mice fed the SFA diet than in the
      other mice and in vivo supplementation of OG-VI was also less effective in
      restoring impaired antibody production in these mice. A diet with a high content
      of SFA may alter nucleotides' action on humoral immune responses, in addition to
      its direct effects on immune functions.

PMID- 8748197
TI  - Effects of intravenous perilla oil emulsion on nutritional status,
      polyunsaturated fatty acid composition of tissue phospholipids, and thromboxane
      A2 production in streptozotocin-induced diabetic rats.
AB  - The effects of a perilla oil (PO) emulsion rich in alpha-linolenic acid,
      administered by intravenous infusion, on nutritional status, fatty acid
      composition, and thromboxane A2 production were compared with those of a soybean
      oil (SO) emulsion in streptozotocin-induced diabetic rats given a fat-free diet
      for 7 days. The PO emulsion improved body weight gain and nitrogen balance
      compared with the SO emulsion and reduced thromboxane A2 production by platelets.
      The PO emulsion also increased the proportion of eicosapentaenoic acid, but
      decreased that of arachidonic acid, in liver and serum phospholipids. Plasma
      insulin concentrations and blood biochemical indices were similar in the two
      groups. An intravenously infused PO emulsion effectively reduces thromboxane A2
      production through changes in the fatty acid composition of liver and serum
      phospholipids, as with oral administration, and improves the nutritional status
      of diabetic rats.

PMID- 8748198
TI  - Total parenteral nutrition in a patient with severe diabetic diarrhea.

PMID- 8748199
TI  - Influence of acidosis on protein metabolism.
AB  - Acidosis is a common clinical condition with both chronic and acute forms.
      Chronic metabolic acidosis induces an increase in protein degradation; however,
      its effects on protein synthesis are less clear. Metabolic acidosis increases net
      whole-body proteolysis by a massive increase in protein degradation and only a
      moderate increase in protein synthesis. Most studies in humans on the relation
      between acidosis and protein metabolism have concentrated on patients with
      chronic renal failure with metabolic acidosis. However, because chronic renal
      failure is associated with other abnormal metabolic conditions such as
      malnutrition, it is difficult to separate out the effects on protein metabolism
      solely due to acidosis. Data on the influence of other forms of acidosis, e.g.,
      respiratory acidosis, diabetic ketoacidosis, and lactic acidosis, on protein
      turnover are sparse. Similarly, data about the influence of acidosis on the
      metabolism of other proteins, such as the liver-produced secretory proteins, are
      lacking. Future research should more vigorously investigate the influence of
      acidosis on protein metabolism in various clinical conditions and the potential
      regulatory effects on the metabolism of secretory proteins. The reversal of
      acidosis might prove to have beneficial effects on protein wasting, and thus
      decrease morbidity and possibly mortality.

PMID- 8748200
TI  - Is LCAT activity a determinant of HDL cholesterol concentrations?

PMID- 8748202
TI  - Medicaid costs drive state health care reform.

PMID- 8748203
TI  - Odds, risks and their relatives.

PMID- 8748204
TI  - Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. 1979.

PMID- 8748205
TI  - How to integrate serum tumor markers into clinical oncologic practice.
AB  - Several serum tumor markers have been studied in different types of epithelial
      cell-associated cancer. The application of these markers in clinical oncologic
      practice is hampered by insufficient sensitivity and specificity in most primary
      tumors. It is important to define which markers contribute to patient management.
      Prostate-specific antigen can be used in prostate cancer patients for screening
      and monitoring advanced disease. Cancer antigen 125 is primarily used for the
      monitoring of combined chemotherapy in ovarian cancer patients. In breast cancer
      patients preoperative levels of cancer antigen 15-3, carcinoembryonic antigen,
      and tissue polypeptide antigen specific do not contribute in prognosis, but
      changes in the levels of these markers predict the clinical outcome in the
      treatment of advanced disease better than UICC criteria. Carcinoembryonic antigen
      and tissue polypeptide antigen specific can detect recurrence in colorectal
      cancer patients earlier than imaging methods. Tissue polypeptide antigen specific
      is sensitive in measuring response to combined chemotherapy in advanced
      gastrointestinal cancer. In bladder cancer, urine levels of cytokeratins are
      sensitive in indicating advanced disease. In small-cell lung cancer neuron
      specific enolase is a good indicator of chemotherapy response. In non-small-cell
      lung cancers, cytokeratins may also predict response in chemotherapy treatment.
      Clinical application of tumor markers in the correct circumstances can omit more
      invasive and costly procedures and will contribute to better patient care.

PMID- 8748206
TI  - Interleukin-1 and interleukin-1 receptor antagonist.
AB  - Cytokines are produced in disease or during immunologic challenge. Some cytokines
      increase host resistance to disease whereas others trigger inflammatory
      processes. Interleukin 1 (IL-1) and tumor necrosis factor (TNF) are pro
      inflammatory cytokines that affect nearly every cell either alone or in a
      synergistic fashion. In animal models of infectious, inflammatory or metastatic
      disease, the role of IL-1 and TNF has been defined by specifically blocking these
      cytokines. For TNF, anti-TNF monoclonal antibodies and soluble receptors reduce
      inflammation and lethality. Antibodies to type I IL receptor, IL-1 receptor
      antagonist (IL-1ra), and soluble IL-1 receptor have been used to reduce the
      severity of disease in various animal models of local and systemic inflammation.
      In a Phase III trial, IL-1ra reduced mortality rate in patients with septic shock
      syndrome by 22%. IL-1ra and soluble receptors to TNF are produced naturally and
      are elevated in the circulation in several diseases. It is unclear whether these
      endogenous levels are sufficient to block IL-1 and TNF from triggering their
      respective cell-bound receptors in disease. IL-1 infusions into patients induce
      circulating levels of IL-1ra but not IL-1. TNF infusions into patients also
      induce high levels of soluble TNF receptors.

PMID- 8748207
TI  - Neuropeptide Y and hypertension.
AB  - Neuropeptide Y is a cotransmitter in the sympathetic nervous system with potent
      contractile effects on blood vessels. The plasma levels of neuropeptide Y-like
      immunoreactivity in patients with severe hypertension (> 120 mmHg) were increased
      compared with the levels in control subjects and were still elevated after long
      term pharmacologic treatment of normotension. Neuropeptide Y stimulated DNA
      synthesis, total cell number, and total protein production in human vascular
      smooth muscle cells through a Y1-receptor. A Gi/G(o)-coupled second messenger
      mechanism seems to be involved, because pretreatment with pertussis toxin
      abolished the mitogenic effect. Neuropeptide Y potentiated the mitogenic effect
      of noradrenaline, and together with adenosine 5'-triphosphate, the sympathetic
      cotransmitters reached a mitogenic effect of approximately 20% of fetal calf
      serum. We have shown that neuropeptide Y, noradrenaline, and adenosine 5'
      triphosphate, apart from their effects on vascular tone, are stimulators of
      vascular smooth muscle cell growth. The receptors that mediate the mitogenic
      effect have been examined. The circulating plasma levels are increased in
      patients with severe hypertension. These findings indicate that the sympathetic
      cotransmitter neuropeptide Y may be of importance in sympathetic vascular
      regulation and involved in pathophysiologic conditions.

PMID- 8748208
TI  - Serum copper, zinc, and iron in patients with malignant and benign pulmonary
      diseases.
AB  - Some environmental factors and diseases have been demonstrated to affect trace
      element homeostasis. Ninety individuals were included in the present study (30
      with bronchogenic carcinoma, 30 with some nonmalignant lung diseases, and 30
      normal healthy controls). Serum copper, zinc, and iron levels were determined by
      the atomic absorption spectrophotometry. Results of this study revealed that
      serum copper was markedly elevated in benign lung diseases followed by bronchial
      carcinoma. Serum zinc was significantly reduced, whereas serum iron was not
      significantly decreased in both benign and malignant lung diseases compared to
      normal healthy controls. As to the sensitivity of the studied elements in lung
      disorders, neither serum copper nor serum iron can be used to detect benign or
      malignant diseases. Serum zinc and copper/zinc ratios showed reasonable values
      for prediction of pulmonary diseases but cannot be recommended as tumor markers
      in lung cancer.

PMID- 8748209
TI  - Significance of trace elements in seminal plasma of infertile men.
AB  - The seminal fluid has the important function as a vehicle for the transportation
      of the spermatozoa through the epididymis, the vas deferens, and urethra and into
      the vagina. Major changes in the level of trace elements like zinc, magnesium,
      and cadmium in semen appear to be related to abnormal spermatozoal function and
      fertilizing capacity. The aim of the study was to evaluate the pattern of trace
      elements in semen of subfertile men compared to levels in the blood. The
      relationship of the trace elements with spermatozoal parameters was also
      evaluated. As part of the infertility evaluation, semen and blood samples were
      collected from 50 males attending the combined infertility clinic at a maternity
      hospital after 3 days' abstinence. Semen analysis and hypo-osmotic swelling tests
      were done on fresh semen samples. The serum and remaining semen sample were
      stored at -20 degrees C until they were analyzed with atomic absorption
      spectrometry. No significant differences occurred in the levels of trace elements
      in normozoospermic, oligospermic, and azoospermic semen. However, significantly
      high levels of cadmium were detected in semen of men who were smokers and had
      asthenozoospermia (p < 0.001) compared with those who had normal motility. We
      conclude that the high level of cadmium in smokers with asthenozoospermia is
      evidence of the possible toxic effect of this trace element and this may be one
      of the causes of asthenozoospermia.

PMID- 8748210
TI  - Human exposure to trace elements through diet.
AB  - During the past several years, we have collected more than 50 total diet samples
      from different socioeconomic groups in Turkey by the duplicate-portion technique.
      The samples were homogenized with a titanium-blade homogenizer, freeze-dried, and
      analyzed for their minor and trace elements by atomic absorption spectrometry and
      by instrumental neutron activation analysis. As a result we have determined
      concentrations of more than 25 elements in total diet and calculated daily
      dietary intakes of these population groups. Sources of trace elements were
      estimated through correlation coefficient and enrichment factor calculations.

PMID- 8748211
TI  - Modulation by selenium supplementation of lipid peroxidation induced by chronic
      administration of adriamycin in rats.
AB  - Adriamycin (doxorubicin) is an antineoplastic drug used to treat various cancers;
      however, its chronic use is accompanied by cardiotoxicity. Previous results
      suggested that free radical formation may contribute to Adriamycin toxicity.
      Adriamycin-induced cardiotoxicity was examined in rats maintained on either
      standard or selenium-supplemented diets. Adriamycin was administered
      intraperitoneally; the cumulative dose was 15 mg/kg body weight. Selenium status,
      glutathione peroxidase activities, vitamin E, and MDA contents were determined on
      red blood cell (RBC) and cardiac homogenates. RBC selenium levels and selenium
      glutathione peroxidase activity were significantly increased in selenium
      supplemented animals compared with control or placebo groups. However, Adriamycin
      treated rats showed a significant decrease in RBC selenium and selenium
      glutathione peroxidase compared with the placebo group. Moreover, treatment with
      Adriamycin increased RBC MDA content, which was attenuated by the selenium
      supplementation. In parallel, RBC vitamin E decreased markedly in the Adriamycin
      treated group and was totally restored by selenium supplementation. Cardiac
      biochemical analyses confirmed the blood results. Thus, a free radical mechanism
      does contribute to Adriamycin cardiotoxicity, and shows the importance of
      balancing selenium levels in Adriamycin-treated subjects to limit Adriamycin's
      action. A decrease in Adriamycin cardiotoxicity with no concomitant decrease in
      its antineoplastic activity would considerably improve the therapeutic benefit of
      the drug.

PMID- 8748212
TI  - Iodine deficiency disorders: a public health challenge in developing countries.
AB  - Iodine as a trace element is an essential nutrient for human growth and
      development. Its potential impact on manpower development in third world
      countries are of special concern, primarily due to iodine deficiency disorders
      (IDD) such as goiter, hypothyroidism, and cretinism. IDD of mild to moderate
      severity are still found in Malaysia. The prevalence ranges from almost zero in
      many developed urban areas to more than 90% in some rural parts of Malaysia,
      especially in Sabah and Sarawak. The endemias were associated with low urinary
      excretion of iodine among the population, indicating poor iodine intake and low
      iodine content in the environment. Water and salt iodination strategies are being
      planned to eradicate the disease by the year 2000.

PMID- 8748213
TI  - Endocrine abnormalities in hemodialysis patients with iron overload: reversal
      with iron depletion.
AB  - The endocrine function was studied in 9 hemodialysis patients with iron overload
      (IO) before and after iron depletion. Diagnosis of IO was established by high
      serum ferritin (> 1100 micrograms/L), high hepatic CT density (> 70 Hounsfield
      units), and excessive iron stores in bone marrow aspirate (grade 6). At the start
      of the study, 8 patients had gonadal failure, 6 of whom had hypothalamopituitary
      disease, and 4 manifested thyroid abnormalities. At the end of the study, the
      hypothalamopituitary function and thyroid abnormalities improved in all patients
      except one who manifested hypothalamic disease. Primary gonadal failure persisted
      in the 8 patients. ACTH stimulation produced adequate increments in plasma
      cortisol at the start and end of the study. Pancreatic (beta cell) function was
      adequate at the end of the study as shown by normal oral glucose tolerance test
      and free insulin increments during the test. The CT scan and follow-up indicated
      significant iron mobilization from the liver, pancreas, and the adrenal glands.
      Hormonal studies were repeated in 4 of the 5 patients who manifested endocrine
      abnormalities and had received recombinant human erythropoietin (rHuEPO), 3 mo
      after discontinuation of the drug. Improvement in the endocrine function
      persisted in those patients. Our results indicated that dialysis patients exposed
      to iron overload are at risk for development of multiple endocrine defects.
      Fortunately, aggressive iron depletion can mobilize iron from these organs and
      reverse some of the defects.

PMID- 8748214
TI  - Keloid and hypertrophic scars: trace element alteration.
AB  - The state of excessive fibroblastic proliferation for wound healing results in
      hypertrophic and keloid scars. It has been well established that some of the
      trace elements (such as zinc) are essential in wound healing, and there are
      appreciable changes in trace elements in various disease states. The levels of
      zinc (Zn), copper (Cu), manganese (Mn), and selenium (Se) in serum, normal skin
      and scar of 40 keloid and hypertrophic scar patients were assessed. There was a
      significant increase of manganese (Mn) level in skin of burn, trauma, and
      surgical incision patients compared to controls with p < 0.0013, p < 0.0001, and
      p < 0.046, respectively. Furthermore, the zinc, copper, and selenium contents of
      the skin in incision patients were decreased significantly when compared to other
      groups. No significant changes occurred regarding serum levels of zinc, copper,
      manganese, and selenium in the different groups. From this study, no
      relationships between the hypertrophic and keloid scar to trace elements were
      found; however, because of the limited numbers of patients, a definite conclusion
      could not be drawn.

PMID- 8748215
TI  - The diagnostic utility of serum ferritin estimation in Nigerian patients with
      primary hepatocellular carcinoma.
AB  - Serum hepatitis B surface antigen (HBsAg) status and ferritin levels were
      measured in three groups of Nigerian subjects: Group A (n = 14) with non
      neoplastic disease (CNLD); Group B (n = 14) with primary hepatocellular carcinoma
      (PHC); and Group C (n = 14) of healthy matched controls. Serum ferritin values
      were lowest in Group C, intermediate in Group A, and highest in the Group B
      patients (all p < 0.05). About 79% of the patients with PHC, 43% of those with
      CNLD, and none (0%) of the healthy controls had hyperferritinemia (serum ferritin
      > 400 ng/ml). Hyperferritinemia and HBsAg positivity coexisted in 15% and 73% of
      the patients with CNLD and PHC, respectively. Hyperferritinemia and HBsAg were
      significantly positively related in the patients with PHC (chi 2 5.09, p < 0.05).
      The predictive indices of hyperferritinemia in chronic liver disease appeared
      superior for PHC than for CNLD, and became somewhat enhanced with coexisting
      HBsAg positivity. These results suggest that serum ferritin could be useful as a
      tumor marker for PHC in Nigerian patients with established chronic liver disease.

PMID- 8748216
TI  - Determination of selected trace elements in foodstuffs and biological materials
      by destructive neutron activation analysis.
AB  - Concentration of trace elements in Nescafe, Fariman sugar, and Sadaf turmeric and
      mercury content in cancerous blood were determined by radiochemical, neutron
      activation analysis. By this separation method levels of 110mAg, 198Au, 203Hg,
      76Se, 51Cr, 24Na, 42K, 99Mo, 122Sb, 82Br, 59Fe, 60Co were measured without
      interference in the gamma spectroscopy. A nondestructive method has also been
      used for the analysis of sodium, potassium, and bromine.

PMID- 8748217
TI  - Nuclear analytical methods in calcified tissue research.
AB  - Various nuclear analytical methods have been developed and applied to determine
      the elemental composition of calcified tissues (teeth and bones). Fluorine was
      determined by prompt gamma-activation analysis through the 19F(rho, alpha,
      gamma)16O reaction. Carbon was measured by activation analysis with 3He ions, and
      the technique of proton-induced x-ray emission (PIXE) was applied to
      simultaneously determine calcium, phosphorus, and trace elements in well
      documented teeth. Dental hard tissues (enamel, dentine, cementum, and their
      junctions) and different parts of the same tissue were examined separately. With
      the use of a proton microprobe, we measured the surface distribution of fluorine
      and other elements on and around carious lesions on the enamel. The depth
      profiles of fluorine, and other elements were also measured right up to the
      amelodentin junction. We discuss the development of various nuclear techniques
      and their applications, mainly in the field of dental health and to some extent
      in the study of the role of lead in mental retardation. We do not mention other
      important areas of calcified tissue research where these techniques could play an
      important role (e.g., in accurate and nondestructive measurements of calcium,
      phosphorus, and other elements in small bone biopsies taken from patients with
      metabolic bone disorders). No suitable chemical method appears to be available
      that can provide accurate assessment of calcium, phosphorus, and other trace
      elements in small bone biopsies. Moreover, the nondestructive nature of the
      nuclear methods has an extra advantage in that the bone samples, which are
      normally rather small in quantity, subsequently can be used for histologic
      examination.

PMID- 8748218
TI  - Major and trace element concentration differences between the right and left
      hemispheres of the "normal' human brain.
AB  - The brain can be divided into many anatomical regions, and the minor and trace
      element distribution across these regions has been shown to be heterogeneous. The
      various functions of the brain such as memory and language have been associated
      with different brain regions, and attempts to correlate brain function with
      elemental composition have been made. Establishing "normal" concentration values
      is a complex task due to the variability of factors such as age, sex, dietary
      intake, environmental exposure, and smoking habits. In establishing the elemental
      concentration of a particular brain region, a mean value from the right and left
      hemispheres of different brains is often used. This is usually due to the lack of
      availability for analysis of the same brain regions from both hemispheres of one
      individual. However, it is known that the right and left hemispheres have
      different functions. Thus, it may be expected that they may have different trace
      element concentrations as well. In this study 13 brain regions were sampled from
      both hemispheres of six elderly individuals, and their major element composition
      was determined by Rutherford backscattering (RBS) analysis, whereas the minor and
      trace element concentrations were obtained by particle induced X-ray emission
      (PIXE) analysis.

PMID- 8748219
TI  - Fatty-acid peroxidation in relation to trace elements in serum of patients with
      homozygous sickle-cell anemia and beta-thalassemia: a gas-chromatographic study.
AB  - Due mainly to a deeply disturbed iron metabolism, intense production of oxygen
      derived free radicals occurs in genetic hemoglobinopathies such as homozygous
      sickle-cell anemia and beta-thalassemia. Together with impairments in the natural
      factors involved in oxy-radical detoxication, this results in intense oxidative
      stress leading to lipid peroxidation in the blood components. In search of
      peroxidation effects, we undertook a gas chromatographic study of both the total
      and phospholipid-bound fatty acids in the serum from sickle-cell disease and beta
      thalassemia patients. Specific alterations of pathologic origin have been
      evidenced in the profiles of total and phospholipidic fatty acids, as well as in
      the elongation-desaturation ratios of the total fatty acids. Results are
      consistent with lipid peroxidations and fatty-acid biosynthesis disturbances in
      both diseases, but more severe in thalassemia than in sickle-cell anemia.
      Increased serum selenium in the latter disease might exert a protective action
      against lipid peroxidation.

PMID- 8748220
TI  - Probucol improves antioxidant activity and modulates development of diabetic
      cardiomyopathy.
AB  - To examine the role of free radicals in diabetic cardiomyopathy, myocardial
      antioxidants as well as lipid peroxide content were examined in rats made
      diabetic with a single injection of streptozotocin (65 mg/kg i.v). At 4 wk, the
      left ventricular peak systolic (LVSP) as well as aortic pressures were depressed
      in the diabetic group. Hearts from diabetic animals showed about a 100% increase
      in thiobarbituric acid reactive substances (TBARS), indicating increased lipid
      peroxidation. This was accompanied by about a 50% decrease in superoxide
      dismutase (SOD) and 60% decrease in glutathione peroxidase (GSHPx) enzyme
      activities. Catalase activity in these hearts showed a small but significant
      increase. Treatment with probucol (10 mg/kg i.p., on alternate days), a known
      lipid-lowering drug with strong antioxidant properties, was initiated 1 d after
      the induction of diabetes and was continued for 4 wk. In probucol-treated
      diabetic animals, LVSP was not different from controls. Probucol treatment caused
      a small but significant improvement in serum insulin and decrease in glucose
      levels as well as increased myocardial SOD, GSHPx, and catalase activities with a
      concomitant decrease in TBARS in the diabetic animals. These data provide
      evidence that diabetic cardiomyopathy is associated with an antioxidant deficit,
      and a better cardiac function due to treatment with probucol may be related to
      the improved insulin levels as well as maintenance of the antioxidant status of
      the heart.

PMID- 8748221
TI  - Radioprotective and antioxidant effects of zinc aspartate and bio-normalizer in
      children with acute myelo- and lympholeukemias.

PMID- 8748222
TI  - Novel copper superoxide dismutase mimics and damage mediated by O2.-.
AB  - Metabolites of oxygen such as superoxide anions (O2.-), hydrogen peroxide (H2O2),
      and hydroxyl radicals (OH.) are potentially damaging to biological systems.
      Univalent reduction of oxygen produces O2.-, which may be converted to H2O2 and
      OH(.). The biological damage mediated by O2.- can be attenuated by a cytosolic
      copper- and zinc-containing enzyme known as superoxide dismutase (SOD). Certain
      transition metal complexes having properties similar to SOD may be useful in
      suppressing such damage. However, known complexes have either been ineffective in
      vivo or may have toxic side effects. We prepared mixed-ligand copper complexes of
      polyamine using biomolecules such as pyridine or imidazoles as secondary ligands.
      The choice of polyamines and biomolecules was made with the aim of producing
      products with low toxicity. Our studies suggest that these copper complexes act
      as mimics of SOD in a variety of O2.(-)-generating systems and may be effective
      SOD mimics for their usage to abrogate such an injury in biological systems. This
      manuscript provides a brief state-of-the-art review on SOD mimics including our
      own studies.

PMID- 8748223
TI  - Effects of copper deficiency and Cu complexes on superoxide dismutase in rats.
AB  - The effect of dietary copper (Cu) deficiency on the antioxidant enzyme superoxide
      dismutase (SOD) was investigated in both erythrocyte and liver samples of 40
      weanling Wistar rats. Groups were fed control (10 mg Cu/kg) or Cu-deficient (0.5
      mg Cu/kg) diets for 7 wk. In this study, dietary copper deficiency did not affect
      growth, food intake, liver size, or hemoglobin levels. Protein concentrations
      were considerably decreased in the livers of the copper-deficient group compared
      to control groups after 7 wk. Erythrocyte SOD activity was not significantly
      different in copper-deficient groups. In contrast, SOD activity was significantly
      reduced in livers of rats consuming the Cu-deficient diet compared to controls.
      The in vitro SOD activities in the presence of five different macro-cyclic copper
      II containing complexes with different stability constants were studied. The
      moderately stable copper complex increased the SOD activity in Cu-deficient liver
      and erythrocyte samples only at wk 7. At wk 6, a significant increase in SOD
      activity in liver samples only was observed. In contrast, at wk 4, no significant
      differences in SOD activity were observed upon addition of Cu complexes. These
      results suggest that the increase in SOD activity may be due to superoxide-like
      action or other properties of this copper complex.

PMID- 8748224
TI  - Effects of bio-normalizer (a food supplementation) on free radical production by
      human blood neutrophils, erythrocytes, and rat peritoneal macrophages.
AB  - Bio-normalizer, a natural Japanese health food prepared by the fermentation of
      Carica papaya, exhibits therapeutic properties against various pathologies
      including tumors and immunodeficiency. To understand the mechanism of bio
      normalizer's therapeutic effects, we studied its action on the production of
      active oxygen species in cell-free systems (the Fenton reaction, the xanthine
      xanthine oxidase system, and the hydrogen peroxide-hypochloride or hydrogen
      peroxide-horseradish peroxidase systems) and by human blood neutrophils and
      erythrocytes and rat peritoneal macrophages. Bio-normalizer efficiently inhibited
      the formation of oxygen radicals in cell-free systems and partly decreased
      spontaneous and menadione-stimulated superoxide production by erythrocytes, but
      manifested both stimulatory and inhibitory effects on oxygen radical release by
      dormant and activated phagocytes (neutrophils and macrophages). We suggest that
      bio-normalizer is able to enhance the intracellular production of innocuous
      superoxide ion and, at the same time, to diminish the formation of reactive
      hydroxyl radicals, perhaps by the inactivation of ferrous ions, the catalysts of
      the superoxide-driven Fenton reaction. We also propose that the normalization of
      an organism's superoxide level is one of the molecular mechanisms of bio
      normalizer activity.

PMID- 8748225
TI  - Selenium and glutathione peroxidase levels in healthy infants and children in
      Austria and the influence of nutrition regimens on these levels.
AB  - Serum selenium values were investigated in 56 formula-fed and in 18 wholly breast
      fed infants. In 14 of these infants, glutathione peroxidase (GSH-Px) was also
      investigated. Determination of selenium and GSH-Px was also done in umbilical
      cord blood of seven healthy newborns. In another 109 infants aged 1-15 yr, serum
      selenium values were investigated. A continuous fall of serum selenium values was
      noted in the first 3 mo of life. Low levels continued until the age of 6 mo with
      a mean of 36% of the umbilical cord vein level. Breast-fed babies of GSH-Px
      showed a less pronounced fall in selenium and had significantly higher levels of
      GSH-Px. GSH-Px activity was reduced from age 5 to 8 mo. Feeding of beikost caused
      a rise in the level of selenium. Children in the age groups 1-15 yr still had a
      significantly lower serum selenium level than adults.

PMID- 8748226
TI  - Effects of vitamin E on the retina and retinal pigment epithelium of IRCS rats.
AB  - A recessive gene defect leads to gradual loss of photoreceptor cells in the
      retinas of a rat strain developed by the Royal College of Surgeons (RCS).
      Previous evidence suggested that retinal degeneration in RCS rats is partly due
      to instability of the lysosomal membranes of the retinal pigment epithelium
      (RPE). Lipid peroxidation contributes to instability of lysosomal membranes. In
      this study, administration of the antioxidant vitamin E retarded the degenerative
      process in RCS rat retinas as evidenced by light- and transmission-electron
      microscopic examination. Photoreceptor cells as well as the RPE were in better
      condition in animals treated with 100 or 150 mg vitamin E/kg body weight daily
      than in untreated animals or animals treated with lower doses. This assertion is
      based on the increased survival of photoreceptor cell nuclei as evidenced by the
      thickness of the outer nuclear layer coupled with a reduction in the number of
      pycnotic nuclei, the conservation of the outer limiting membrane, and the
      presence of phagosome-like structures in the RPE. These and previous results in
      this strain of rats lead us to propose that lipid peroxidation plays an important
      role in the pathogenesis of this degenerative process of the retina.

PMID- 8748227
TI  - Protective effect of the superoxide scavenger EUK8 against ultrastructural
      alterations induced by ischemia and reperfusion in isolated rat hearts.
AB  - We have recently shown that iron overload may increase the susceptibility of
      isolated rat hearts to ischemia and reperfusion, an effect that could be related
      to an iron-dependent activation of the Fenton reaction, thus producing cytotoxic
      hydroxyl radicals. The purpose of our study was to investigate the influence of
      EUK8, a new catalytic scavenger of superoxide anions that is similar to
      superoxide dismutase, on cardiac ultrastructural alterations associated with
      reperfusion. Experiments were carried out ex vivo in iron-overloaded rat hearts
      perfused at a constant flow rate (11 ml/min) with (EUK8) or without (control)
      EUK8 (50 mumol/L) throughout the perfusion. Hearts were submitted to 15 min
      global normothermic no-flow ischemia and then reperfused for 15 min before
      examination. For each heart, six micrographs at a magnification of x 11,300 were
      used to quantitate ultrastructural alterations. In our experimental model, EUK8
      prevented some of the ultrastructural modifications associated with ischemia and
      reperfusion in iron-overloaded rat hearts. This beneficial effect could be
      related to the limitation of reperfusion-induced oxygen free radical production
      under the effect of EUK8.

PMID- 8748228
TI  - A bone marrow peroxidation study on low-dose irradiated rats.
AB  - The aim of this work was to study the modification of some biochemical parameters
      induced in animals irradiated by in vivo contamination with tritiated water
      (HTO). Four groups of animals were chronically irradiated by ingestion over 145
      d. Irradiation doses were, respectively, 4, 9, 27, and 49 cGy. Another group was
      a control (nonirradiated) group. We followed the peroxidation level in bone
      marrow tissue using the thiobarbituric acid test, and results are expressed by
      malondialdehyde (MDA) concentration (mol MDA/mg protein). We adapted known
      methods to the study of a very small amount of tissue. We also followed the
      variation of deoxyribonucleic acid (DNA) concentration (mol/mg protein) in the
      tissue. The studied parameters seem to be influenced by irradiation, but not
      necessarily in a monotonous way with respect to irradiation dose. The peroxide
      level reported to mg protein is modified in a statistically significant way only
      for the highest dose. DNA content was found to decrease for irradiated rats
      starting with the lowest dose, and the peroxide level reported for DNA content
      increased for irradiated animals.

PMID- 8748229
TI  - Free radicals, ceruloplasmin, and copper concentration in serum and aortic tissue
      in experimental atherosclerosis.
AB  - It has been suggested that the increase in concentration of blood lipid peroxides
      may be a risk factor for atherosclerosis. Our research was conducted to study the
      effect of cholesterol feeding on lipid peroxides, ceruloplasmin, HDL-cholesterol,
      serum unesterified fatty acids, and copper concentration in serum and aortic
      tissue in rats. In the animals fed a cholesterol-supplemented diet, the mean
      values of serum lipid peroxide, ceruloplasmin, serum copper, and unesterified
      fatty acids were increased significantly (p < 0.01) as compared to the control
      group. At the same time, HDL-cholesterol concentration was significantly
      decreased in rats fed a diet enriched with cholesterol (p < 0.01) compared to the
      control group. A significant decrease of copper concentration in aorta was also
      observed in these animals versus controls. Correlations between ceruloplasmin and
      lipid peroxides as well as copper were statistically significant in these
      animals. At the same time, antioxidant activity in blood was two times higher as
      compared to controls. Results of this study provide the support for applying
      these determinations in atherosclerosis monitoring.

PMID- 8748230
TI  - Study of chemical element behavior in health and disease by means of neutron
      activation analysis and multivariate statistics.
AB  - An attempt was undertaken to estimate the contribution of individual chemical
      elements to the rise of arterial hypertension. Instrumental neutron activation
      analysis was used to determine the concentrations of 23 chemical elements in hair
      of patients and healthy subjects. Mean concentrations as well as relationships
      between elements in both groups were calculated and compared. Discriminant
      function was obtained, which allows the division of patients and healthy subjects
      into two groups.

PMID- 8748231
TI  - Tumor-induced changes in host metabolism: a possible marker of neoplastic
      disease.
AB  - A large number of "biologic markers" for cancer have been described, including
      tumor-associated antigens, ectopic hormones, enzymes, and effects of tumor on the
      host's metabolism. Although tumors may metabolically differ from each other, they
      may induce similar derangements in glucose, lipid, and protein metabolism in the
      host. In particular, changes in carbohydrate metabolism may induce glucose
      intolerance that may be early and easily detected using an oral glucose tolerance
      test. Hypertriglyceridemia and reduced exogenous lipid clearance may represent an
      early marker of deranged lipid metabolism. Changes in protein metabolism, as
      reflected by plasma amino acid profile, may also represent a new diagnostic tool
      for cancer. Among other amino acids, free tryptophan seems to be the best
      candidate as a new useful marker for monitoring neoplastic disease. It is
      conceivable that, based on the understanding of the differences in plasma amino
      acid profiles, more specific and rational antineoplastic strategies may arise.

PMID- 8748232
TI  - An atomic basis of cancer (V): A new marker in animal tumors.
AB  - Particle-induced X-ray emission (PIXE) analysis can be applied to mark (or to
      localize) a cancer lesion in a benign environment in test animals. We synthesized
      hematoporphyrin derivative (HPD) with rare earth metals to form lanthanide-HPD to
      enhance the localizing efficiency. The sensitive PIXE detection of trace elements
      in amounts on the order of nanograms or less could possibly be used to probe
      carcinogenesis at the level of the cell. To explain the present approach, we
      present the results of an experiment in which we used paraseodynium-HPD
      localizer.

PMID- 8748233
TI  - Neuroblastoma screening: labeling of HVA and VMA for stable isotope dilution gas
      chromatography-mass spectrometry.
AB  - Neuroblastoma is a curable tumor if detected early enough. Therefore, a screening
      test is performed in Austrian infants by analyzing urine samples collected and
      dried on filter strips. Screening is performed by measuring homovanillic acid
      (HVA) and vanillylmandelic acid (VMA) using the enzymatic immunoassay chemistry
      (EIA) method and reexamining the elevated values by high-performance liquid
      chromatography. Both methods, however, give a relatively high number of false
      positive results. Therefore, the positives are reexamined by stable isotope
      dilution (SID) gas chromatography-mass spectrometry (GC-MS), which is the most
      sensitive and precise method in clinical chemistry. The labeled substance is
      added as an internal standard to the sample; it has nearly identical chemical and
      physical properties as the natural analogue, undergoes the entire preparation
      step, and is detected simultaneously with the natural analogue by the same
      detector, namely the mass spectrometry, given by a difference in molecular
      weight. All loss is compensated in this way by the final calculation. At present,
      HVA but not VMA can be purchased labeled with deuterium, so we started with our
      method using deuterated HVA as the internal standard for both HVA and VMA.
      Because the coefficient of variation is not sufficient for VMA, we try to label
      VMA via different labeling procedures; for example, 1) exchange of the aromatic H
      against D by incubation with DCI or in alkaline R-OD or LiOD or 2) exchange of
      phenolic 16OH against 18OH by reaction with H2(18)O in an acidic environment and
      at high temperatures. Carboxylic 16O can be exchanged against 18O.

PMID- 8748234
TI  - New insights into the stem cells and the precursors of the gastric epithelium.
AB  - It is believed that stomach neoplasia represents the end result of a multistep
      journey that starts with derangement of the cellular proliferation and commitment
      program of the epithelium. The epithelium is normally made up of a single layer
      of cells that invaginates to form numerous short pits continuous with long
      tubular glands divisible into isthmus, neck, and base regions. Three main cell
      lineages populate these pit-gland units: 1) mucus-secreting pit, 2) pepsinogen
      secreting zymogenic, and 3) acid-secreting parietal cell lineages. The immature
      cells of the unit are located in the isthmus region; they include
      undifferentiated stem cells that undergo frequent asymmetric mitosis to reproduce
      themselves and give rise to two partially committed precursors: 1) prepit-cell
      precursors, which become prepit cells in the isthmus and then migrate outward
      into the pit and mature into pit cells, and 2) preneck cell precursors, which
      become preneck cells in the isthmus and then migrate inward to the neck region
      and transform into neck cells. The latter continue their inward migration and
      eventually reach the base region where they gradually change their phenotype
      through a prezymogenic step to become zymogenic cells. The stem cells, as well as
      the prepit and preneck cell precursors, share in the production of preparietal
      cells that, in the isthmus, mature into parietal cells and then migrate outward
      into the pit or inward into the neck and base. The stem cells also give rise to
      preenteroendocrine and precaveolated cells. These become, respectively,
      enteroendocrine and caveolated cells that proceed to follow the bidirectional
      migratory route of parietal cells. The production of rare nonproliferating
      preparietal cells is enhanced after blocking the secretory activity of their
      mature forms by continuous infusion of the histamine H2-receptor antagonist,
      ranitidine, for 42 h. Thus, the presence of active mature parietal cells is
      necessary to maintain the normal cellular proliferation and commitment program in
      the gastric epithelium.

PMID- 8748235
TI  - Five-year survival versus initial concentrations and longitudinal serum CEA
      patterns in patients with colorectal carcinoma.
AB  - Patients (n = 464) with colorectal carcinoma in stages A to D2 were studied; 230
      had CEA determined preoperatively and 433 serially. Actuarial life table analysis
      and the Mantel-Cox test showed that overall 5-yr survival was 59.2% and that the
      differences among the stages were highly significant. Survival rates for patients
      with CEA over the cutpoints at 3.2, 5, 10, and 20 ng/ml decreased from 53.8% to
      21.9%. When analyzed in Cox multivariate regression, stage, initial CEA, age, and
      location of cancer affected survival. Postoperatively, three CEA patterns were
      found: 1) CEA was always normal; 2) initially elevated CEA was decreasing to the
      normal range to remain so thereafter; or 3) CEA started to increase from any
      nadir some time after surgery. The 5-yr survival rate was 73.3% for patients with
      the normal, 44.5% with the decreasing, and 30.1% with the increasing CEA pattern.
      When the postoperative CEA, pattern was added to the preoperative covariates in
      196 patients for whom both the initial CEA, and postoperative patterns were
      available, only the stage, postoperative CEA pattern, and location of cancer
      affected survival. After elimination of initial CEA 433 patients with
      postoperative serum were analyzed, and again, only stage, postoperative CEA
      pattern, and location of cancer appeared to affect survival. Stage of disease,
      initially elevated serum CEA, age over 60 yr, location of cancer in the rectum,
      and CEA increasing after surgery appear to be independent ominous prognostic
      indicators.

PMID- 8748236
TI  - Role of basic fibroblast growth factor in prostatic tumors.
AB  - Compared with normal prostatic tissue, the level of basic fibroblast growth
      factor (bFGF) is elevated in prostatic tumors. This suggests that bFGF may play a
      role in the development of prostatic neoplasms. The current study was undertaken
      to identify the cellular distribution of bFGF in benign prostatic hyperplasia
      (BPH) and prostatic carcinoma using a polyclonal antiserum against recombinant
      bFGF. In paraffin sections of prostatic tumors immunoreactive bFGF was found in
      fibroblasts, smooth muscle cells, and endothelial cells. Distinct staining was
      seen in most nuclei of these cells and a less intense immunoreaction occurred in
      the cytoplasm of smooth muscle cells. No immunostaining was seen in prostatic
      epithelial cells of prostatic tumors whether benign or malignant. With
      digoxigenin-labeled oligonucleotides in nonradioactive in situ hybridization, the
      presence of mRNA for bFGF was shown in smooth muscle cells of the stroma,
      suggesting that these cells are the main source of bFGF in BPH. Because no
      immunostaining for bFGF was obtained in the carcinoma cells, a specific role for
      bFGF cannot be seen for the development of malignant prostatic tumors.

PMID- 8748237
TI  - Multivariate analysis of DNA ploidy, steroid hormone receptors, and CA 125 as
      prognostic factors in ovarian carcinoma: a prospective study.
AB  - The prognosis in ovarian cancer patients remains poor, and there is a need to
      identify patients who are less likely to respond to treatment. In a prospective
      study of patients with ovarian carcinoma treated by a standard protocol,
      variables such as age, tumor type, International Federation of Gynecology and
      Obstetrics stage, histologic grade, results from flow cytometry, receptors for
      estrogen (ER) and progesterone (PR), and serum CA 125 were correlated to relapse
      and survival. Univariate analysis revealed that stage, histologic grade, DNA
      ploidy, ER, PR, and CA 125 were of significant association to survival, but only
      stage, DNA ploidy, PR, and CA 125 were found to be of significant value to
      relapse. Multivariate analysis identified DNA ploidy as an independent prognostic
      variable for both relapse and survival.

PMID- 8748238
TI  - Primary Ki-1 lymphoma of the skin: expression of growth hormone receptors.
AB  - The biological significance of growth hormone (GH) in the physiology and
      pathophysiology of the immune system is not established. To address the site and
      mode of action through which GH exerts its effects on lymphocyte tumors, we
      applied a well-characterized monoclonal antibody directed against the hormone
      binding site of the receptor and were able to further characterize the tumor by
      immunohistochemical localization of GH receptors. Cutaneous T cell lymphomas were
      identified by histologic and immunomorphologic diagnosis according to the updated
      Kiel classification, with the application of monoclonal antibodies. Nodular
      tumors of the skin, identified as highly malignant Ki-1 lymphomas of large
      anaplastic cells, had intense GH receptor immunoreactivity. The presence of GH
      receptors in these proliferating tumor cells supports the hypothesis that GH is
      involved in paracrine-autocrine mechanisms acting locally in regulating
      peripheral T cell lymphoma tumor growth.

PMID- 8748239
TI  - Potential usefulness of biotinylated neoglycoproteins as tumor markers.
AB  - We used several biotinylated neoglycoproteins as tumor markers to detect and
      localize endogenous carbohydrate-binding proteins in cultured hepatoblastoma,
      melanoma, and bladder carcinoma tumor cells. The neoglycoproteins used consisted
      of cellobiose, fucose, N-acetyl-galactosamine, N-acetyl-glucosamine, lactose,
      maltose, mannose, melibiose, and xylose. In addition, naturally occurring
      asialofetuin that was chemically disialylated was also used. Binding to the
      cultured tumor cells was made visible with the avidin-peroxidase technique.
      Depending on the type of neoglycoprotein used, markedly different expression of
      cytoplasmic and nuclear receptors for sugars (endogenous lectins) was obtained
      from rat hepatoblastoma, human melanoma, and bladder carcinoma tumor cells. The
      most pronounced staining differences were documented for asialofetuin and the
      neoglycoproteins containing fucose, N-acetyl-galactosamine, and lactose.

PMID- 8748240
TI  - Expression of galactosyltransferase in prostatic tumors.
AB  - Galactosyltransferase (GalTase) has been discovered on a variety of cells where
      it is believed to be involved in cell-cell adhesion and cell-substratum adhesion
      as well as in metastasis of carcinoma cells. This immunohistochemical study was
      undertaken to identify the topography and the cellular distribution of GalTase in
      normal prostatic tissue, benign prostatic hyperplasia (11 cases), and prostatic
      carcinoma (26 cases). Immunoreactive GalTase was found to be exclusively
      associated with carcinoma cells and with premalignant epithelial cells in
      prostatic hyperplasia. In highly differentiated carcinomas, most of the carcinoma
      cells are positive for GalTase, whereas in poorly differentiated tumors, GalTase
      immunoreactivity was restricted to a subset of carcinoma cells with obviously
      invasive behavior. At the cellular level, GalTase was localized in the cytoplasm
      and at the cell membrane. In sections of normal prostatic tissue, as well as in
      unaltered acini of prostatic hyperplasic tissue, GalTase was not expressed.
      Fibroblasts, smooth muscle cells, and endothelial cells of the prostatic stroma
      were also consistently negative. With the use of immunoblots, we could confirm
      the presence of GalTase with a molecular mass of 45 kDa in the extracts of benign
      prostatic hyperplasic tissue and in prostatic carcinoma tissue but not in normal
      prostatic tissue. The results of our immunohistochemical study suggest that
      GalTase is a valuable marker to diagnose neoplastic transformation in prostatic
      tissue.

PMID- 8748241
TI  - Salivary epidermal growth factor concentration in thyrotoxicosis.
AB  - Epidermal growth factor (EGF) was first isolated from the mouse submaxillary
      gland, and later from human urine. The synthesis of mouse EGF is stimulated by
      thyroid hormone and inhibited by antithyroid therapy. EGF in turn stimulates the
      growth of thyroid cells. The objective of the present study was to determine
      whether salivary EGF levels are affected by thyroid hormone level in man.
      Unstimulated saliva was obtained from 13 (1 male, 12 females) untreated
      thyrotoxic patients (age 19-64 yr) and from 21 (2 males, 19 females) healthy
      controls (age 19-68 yr). After centrifugation at 1000 x g, the supernatants were
      assayed for human (h) EGF in a homologous radioimmunoassay. The mean +/- SEM
      concentration of hEGF was 0.42 +/- 0.05 nmol/L in controls compared with 0.71 +/-
      0.25 nmol/L in thyrotoxic patients (p > 0.05). Thyrotoxic patients with goiter
      secreted significantly higher concentrations of hEGF (0.92 +/- 0.24 nmol/L) in
      saliva than did euthyroid controls or nongoitrous thyrotoxic patients (0.31 +/-
      0.11 nmol/L, p < 0.01).

PMID- 8748242
TI  - Metal replacement in DNA-binding zinc finger proteins and its relevance to
      mutagenicity and carcinogenicity through free radical generation.
AB  - Carcinogenesis induced by metals is well documented, but the mechanism of cancer
      induction is not clear. It is known that transition metals can damage DNA by free
      radicals generated by Fenton reaction. We are investigating a class of DNA
      binding proteins, known as zinc finger proteins, which act as transcription
      factors binding specifically to short DNA-sequences and controlling the
      transcription of a number of genes. We have demonstrated the ability of metals
      such as cobalt, cadmium, copper, nickel, and iron to substitute for zinc in zinc
      finger protein. The results gave further insight on the structural contribution
      of metal toward DNA-binding and identified metal interactions that may be of
      relevance to metal-induced DNA damage and carcinogenesis. The key to the
      mechanism of metal-mediated carcinogenesis is the enhancement of cellular redox
      processing by metals. Cobalt and iron in the presence of H2O2 catalyze the
      degradation of deoxyribose and induce DNA damage. Thus, a redox metal substituted
      for zinc in the zinc finger protein is expected to generate free radicals to
      cause DNA damage. Consequently, such metals bound to a DNA-binding protein
      generating potentially harmful free radicals in close proximity to DNA may be of
      relevance to the toxicity and carcinogenicity of these metals.

PMID- 8748243
TI  - Sporadic occurrence of nondeletion Prader-Willi syndrome in two cases: a female
      with maternal uniparental disomy and a male with complex chromosomal
      rearrangement.
AB  - We report here two cases of nondeletion Prader-Willi syndrome (PWS). Case 1 is a
      9-yr-old female patient with classical features of the syndrome and
      cytogenetically normal chromosome 15. DNA analysis using polymorphic probes for
      Prader-Willi Critical Region (PWCR) showed absence of paternal alleles while
      maternal uniparental isodisomy (UPisoD) was confirmed. This is the first report
      of nondeletion PWS with uniparental disomy (UPD) in the population of Kuwait. The
      second case with Prader-Willi syndrome-like features had normal chromosome 15 but
      showed familial complex chromosomal rearrangement (CCR) involving chromosomes 13,
      19, and 20 inherited from his mother. No paternal deletion or UPD disomy was
      observed after DNA molecular analysis. This is a case of "atypical" PWS with no
      cytogenetic or molecular abnormality for PWCR. The two cases represent two
      different mechanisms associated with nondeletion PWS.

PMID- 8748244
TI  - Isolation and characterization of the genes of pathogenic mycobacteria that
      express antigens for T cell reactivity.
AB  - Tuberculosis and leprosy are caused by Mycobacterium tuberculosis and
      Mycobacterium leprae, respectively. Identification and characterization of the
      genes expressing proteins that stimulate Th1-type cells is required to understand
      the mechanisms involved in protection from mycobacterial diseases. We isolated
      several recombinant genes from recombinant DNA libraries that expressed antigens
      recognized by well-characterized monoclonal antibodies. We first used these
      isolated recombinants to show that many of these genes expressed antigens with T
      cell reactivity. Most of the genes in the lambda gt11 system were truncated at
      the amino terminus. Full-length genes were isolated from libraries in other
      systems and sequenced. Four of the full-length genes were homologous to heat
      shock proteins of eukaryotes and prokaryotes. We also screened the recombinant
      DNA libraries directly with T cell probes for antigens that may not be recognized
      by antibodies. We isolated one gene expressing an epitope recognized by T cells
      reactive with M. tuberculosis, M. leprae, and M. bovis BCG but not with other
      mycobacteria. All recombinant proteins were presented to T cells in association
      with multiple HLA-DR molecules. The responding T cells were the Th1 type with
      long-lasting memory. The protein products of these genes, either by themselves or
      expressed in suitable vaccines, may be used to protect against tuberculosis and
      leprosy.

PMID- 8748245
TI  - Identification of mycobacterial peptide epitopes recognized by CD4+ T cells in
      association with multiple major histocompatibility complex class II molecules.
AB  - The mycobacterial 18-, 28-, and 65-kDa proteins are recognized by T cells in
      association with multiple class II HLA-DR molecules of the major
      histocompatibility complex (MHC). To identify the epitopes recognized by T cells
      in association with multiple HLA-DR molecules, we established CD4+ T cell lines
      and clones and tested them with overlapping synthetic peptides corresponding to
      the entire amino acid sequence of the 18- and 65-kDa antigens and to the carboxy
      terminus of the 28-kDa antigen. The T cell lines established against the 18-kDa
      antigen recognized three different epitopes, one of which was recognized in the
      presence of antigen-presenting cells from several allogeneic donors. The 65-kDa
      antigen-reactive T cell lines responded to nine different peptides, two of which
      were promiscuous with respect to MHC restriction. The T cell clones responding to
      the 28-kDa antigen proliferated in response to a single peptide from the carboxy
      terminus. This peptide was recognized by T cell clones in association with HLA
      DRw53, which is coexpressed in individuals expressing HLA-DR4, HLA-DR7, and HLA
      DR9. The T cells activated in response to the mycobacterial antigen from
      vaccinated donors belonged to the protective Th1 subset; hence, the peptides
      recognized in association with multiple HLA-DR molecules should be useful in
      subunit vaccines against mycobacterial diseases.

PMID- 8748246
TI  - Recognition of mycobacterial HSP65 in association with HLA-DR4 is not sufficient
      for autoreactivity.
AB  - The mycobacterial heat shock protein 65, class II major histocompatibility
      complex molecule HLA-DR4, and T cells have been implicated in autoimmunity.
      However, there has been no direct demonstration of the recognition of the heat
      shock protein 65 by T cells in association with HLA-DR4. In this study, we
      established T cell lines and a large number of T cell clones from healthy
      subjects vaccinated with killed mycobacteria. Among these subjects, three were
      HLA-DR4 positive, and the T cell lines and clones from these subjects responded
      to the mycobacterial heat shock protein 65. HLA-restriction studies were done
      with well-characterized anti-HLA class I, anti-HLA-DR, and anti-HLA-DQ
      antibodies. Only anti-HLA-DR antibodies inhibited the antigen-induced response of
      the T cell lines and clones to heat shock protein 65. When HLA-DR-typed
      allogeneic cells were used as antigen-presenting cells, the T cell clones from
      only one of the individuals were found to be HLA-DR4 restricted. To identify the
      epitopes recognized by these T cell clones, synthetic peptides were synthesized
      covering the entire sequence of mycobacterial heat shock protein 65. When tested
      with the heat shock protein 65-reactive T cell clones, peptides from five
      different regions of heat shock protein 65 stimulated the T cell clones in
      association with HLA-DR4. However, it is difficult to predict the role of HLA-DR4
      restricted mycobacterial heat shock protein 65 peptides in autoimmunity from our
      studies, because the T cell clones were established from a healthy donor, and the
      peptides belonged to the regions that do not share sequence homology between the
      mycobacterial and human heat shock protein 65 or other proteins.

PMID- 8748247
TI  - Polymerase chain reaction targeting of single- and multiple-copy genes of
      mycobacteria in the diagnosis of tuberculosis.
AB  - Tuberculosis is a worldwide health problem of major concern. Direct detection of
      Mycobacterium tuberculosis in clinical specimens is the best approach to identify
      the causative agent. Identification of M. tuberculosis by culture is the gold
      standard, but the results are delayed for days to weeks. Microscopic examination
      of smears is quite fast, but a sample must contain a large number of M.
      tuberculosis (> 7.5 x 10(3) organisms/ml) for smear positivity. To diagnose
      tuberculosis specifically within 1 d of receiving clinical specimens, we have
      established multiplex polymerase chain reaction (MPCR) assays by targeting DNA
      fragments in the genes present in single or multiple copies in the M.
      tuberculosis genome. The MPCR results are available within a few hours, and the
      detection limit for different targets ranges between 2 and 200 organisms. The
      targets selected in the MPCRs could differentiate between M. tuberculosis complex
      and other mycobacteria from culture-grown specimens. The MPCRs were compared with
      microscopic examination of smears and culture in the diagnosis of tuberculosis.
      Coded sputum samples from suspected tuberculosis patients were tested. The codes
      were broken at the end of the study and the results were compared. All the
      samples negative for smear and/or culture were also negative by multiple-copy
      gene MPCRs (specificity = 100%), whereas the single-copy gene MPCR showed 98%
      specificity. With respect to sensitivity, compared with culture, the single-copy
      gene MPCR showed a sensitivity of 92%, whereas the three- and two-band multiple
      copy gene MPCRs exhibited sensitivities of 87% and 93%, respectively. These
      results suggest that the MPCRs could be helpful in early and specific diagnosis
      of pulmonary tuberculosis.

PMID- 8748248
TI  - Genetic transformation of mycobacteria by homologous recombination.
AB  - Mycobacteria are highly potent adjuvants; therefore, expression of foreign genes
      in mycobacteria provides a delivery system to induce strong immune responses
      against foreign proteins. In this study we report transformation of Mycobacterium
      smegmatis by homologous recombination using pUC19-based plasmid vectors with pyrF
      gene of M. smegmatis (pY6001) or pyrF gene disrupted by introducing the
      aminoglycoside phosphotransferase (aph) gene (pY6002). Both of these plasmids
      were used to transform the host cells by electroporation. The transformation and
      selection conditions were optimized with respect to cell number, stage of cell
      growth, DNA concentration, postelectroporation incubation time, and kanamycin
      concentration. With the plasmid Y6002, the transformation was usually a result of
      single crossover (class I transformants) and only 5% transformants were generated
      by double crossover (class II transformants). The double crossover led to the
      replacement of wild-type pyrF gene with the aph-disrupted pyrF gene. The gene
      replacement could also occur by resolution of the class I transformants into
      class II, but at a very low frequency. Further experiments were done to determine
      if the wild-type genotype could be rescued by retransformation with pY6001.
      Similar transformation efficiencies, as reported above, were obtained, but the
      frequency of double crossover increased to 35%. This transformation strategy
      provides a way by which the mycobacteria transformed with foreign genes will not
      require drug selection, a trait preferred to develop recombinant vaccines.

PMID- 8748249
TI  - Cytokines and feeding suppression: an integrative view from neurologic to
      molecular levels.
AB  - Cytokines are released from activated cells during acute and chronic pathologic
      processes including infection and malignancy. These processes and immunotherapy
      with cytokines are frequently accompanied by feeding suppression. The
      intracerebroventricular (ICV) microinfusion of low doses of interleukin 1 beta
      (IL-1 beta) decreases short- and long-term food intake by reducing meal size and
      meal duration; high amounts also decrease meal frequency and prolong intermeal
      intervals. The ICV microinfusion of interferon (IFN) suppresses only short-term
      feeding by reducing meal size and meal duration; IL-8 suppresses short-term
      feeding by reducing meal size. Bacterial lipopolysaccharide also reduces meal
      size. IL-1 beta is significantly more potent than IFN, IL-8, and other cytokines.
      Evidence also shows that only a subset of cytokines released during pathologic
      processes participate in the regulation of feeding. These behavioral effects of
      cytokines are blocked by the appropriate receptor antagonists and monoclonal
      antibodies. Cytokines affect the hypothalamus and this may result in feeding
      suppression. IL-1 beta and IFN act directly and specifically on the glucose
      sensitive neurons in the ventromedial hypothalamic nucleus (a "satiety" site) and
      the lateral hypothalamic area (a "hunger" site). Pathophysiologic concentrations
      of IL-1 beta and IL-2 in the cerebrospinal fluid inhibit the calcium channel
      current in neurons. It is essential to characterize the mechanisms by which
      cytokines induce feeding suppression to understand appetite suppression during
      disease and immunotherapy.

PMID- 8748250
TI  - Correlation between food intake and cerebrospinal fluid interleukin 1 alpha in
      anorectic tumor-bearing rats.
AB  - Anorexia is observed in 50% of cancer patients; however, the pathogenesis for
      cancer anorexia is unclear. We postulate that centrally acting cytokines play a
      role in the pathogenesis of cancer anorexia. To test our hypothesis we determined
      whether central interleukin 1 alpha (IL-1 alpha) was related to anorexia in tumor
      bearing (TB) rats. Fischer 344 rats were inoculated with either 1 ml of 1 x 10(6)
      trypan blue viable methylcholanthrene-induced sarcoma cells (TB rats) or normal
      saline (non-tumor-bearing [NTB] rats). Rats were placed into individual metabolic
      cages equipped with an Automated Computerized Rat Eater Meter that continuously
      measured food intake. When TB rats became anorectic, TB and NTB rats were
      anesthetized and cerebrospinal fluid (CSF) was collected. IL-1 alpha was
      measured. Food intake in TB was 7.1 +/- 1.1 g, whereas that in NTB was 12 +/- 1.1
      g (p < 0.05). Eight of the 13 TB rats had detectable concentrations of CSF IL-1
      alpha; the mean CSF IL-1 alpha concentration for TB rats was 73.2 +/- 17.3 pg/ml.
      In contrast, none of the NTB rats (n = 11) had detectable concentrations of CSF
      IL-1 alpha. CSF IL-1 alpha concentrations correlated inversely with food intake.
      Data suggest a link between CSF IL-1 alpha and food intake in anorectic TB rats.

PMID- 8748251
TI  - Relationship between interleukin-1 and cancer anorexia.
AB  - Interleukin-1 (IL-1) induces anorexia via direct action in the brain, and its
      participation in the pathogenesis of cancer-associated anorexia has been
      hypothesized. Because the functional ablation of the ventromedial nucleus of
      hypothalamus (VMH), where IL-1 receptors have been detected, reverses cancer
      associated anorexia in tumor-bearing (TB) rats, we hypothesize that cancer
      anorexia involves the direct effect of IL-1 on the VMH. To test this hypothesis,
      we investigated whether the intra-VMH injection of the IL-1 receptor antagonist
      (IL-1ra) improves food intake in anorectic TB rats. Sixteen Fischer rats
      (approximately 300 g/BW) were injected s.c. with 10(6) trypan-blue viable
      methylcholanthrene sarcoma cells, and then individually caged. Chow and water
      were freely available, and food intake was recorded throughout the study. Normal
      food intake was measured in 8 more rats, injected s.c. with normal saline. Tumor
      developed in all rats. When TB rats became anorectic, they were randomly assigned
      to either treatment or control groups. Using stereotaxic techniques, 25 ng of IL
      1ra dissolved in normal saline (TB-IL-1ra; n = 8), or an equal volume of normal
      saline (TB-NS; n = 8) was injected bilaterally into the VMH. After surgery, rats
      were caged and changes in food intake recorded. At study's end, rats were
      sacrificed and brains removed for histological confirmation of injection sites.
      In the TB-NS group, food intake decreased with the occurrence of anorexia. In
      contrast, the intra-VMH injection of IL-1ra reduced the severity of cancer
      anorexia, significantly improving food intake in TB-IL-1ra rats. Data indicate
      that centrally acting IL-1 plays a significant role in the development of cancer
      anorexia.

PMID- 8748252
TI  - Ascorbate effect on cytokine stimulation of HIV production.
AB  - We have recently shown that ascorbic acid (AA) suppresses the production of HIV
      in a latently infected T-lymphocytic cell line (ACH-2) following stimulation with
      the tumor promoter, PMA. To evaluate the effect of ascorbic acid on virus
      activation following treatment with inflammatory cytokine, we tested tumor
      necrosis factor alpha (TNF-alpha) whose levels are elevated in patients with
      HIV/AIDS. ACH-2 cultures, pretreated with various nontoxic concentrations of
      ascorbate or AZT were stimulated for 2 h with TNF-alpha, and incubated further
      with fresh supplements of ascorbate or AZT. At 24 to 48 h post-treatment, the RT
      activity released into culture supernatant was determined. Results showed that
      TNF-alpha alone caused approximately 13- to 16-fold stimulation in the level of
      extracellular RT. Pretreatment with ascorbic acid at 200 micrograms/ml caused a
      little more than about 2- to 4-fold reduction in extracellular RT levels. Most
      remarkably, exposure to 300 micrograms/ml ascorbate resulted in approximately 5-
      to 10-fold lowering of the extra-cellular RT titer. In contrast, no significant
      suppression in extracellular RT levels was seen with concentrations of AZT in the
      range of 1-5 micrograms/ml.

PMID- 8748253
TI  - The comparative value of interleukin-4 in sera of women with preeclampsia and
      cord sera.
AB  - Cytokines are of central importance in the regulation of immunity, inflammation,
      tissue remodeling, and embryonic development. Uncontrolled or excessive cytokine
      production may contribute to the pathophysiology of acute and constant
      infections, autoimmune disease, and neoplasia. Interleukin-4 was first observed
      as a costimulator of B-cell DNA synthesis in response to antiimmunoglobulin M
      antibodies. Within hours of contact with interleukin-4, resting B cells and
      macrophages increase their expression of the class II histocompatibility antigen
      needed for immune cell interaction. The aim of this study was to evaluate the
      levels of interleukin-4 in the sera of preeclamptic women and the cord blood of
      their newborn infants. Five milliliters of blood were withdrawn from the cubital
      vein of 25 women with preeclampsia at 24 and 36 wk gestation, at term, and just
      before onset of labor or in early labor. At delivery, cord blood was withdrawn
      from each woman's corresponding newborn. The control group was 25 women without
      any obstetric complication. Interleukin-4 levels were significantly higher in the
      preeclamptic women than the control women (p < 0.05). Similarly, the interleukin
      4 level was significantly higher in the maternal blood of the preeclamptic women
      than in the cord blood of their newborns (p < 0.01). Because interleukin-4
      increases the expression of class II histocompatibility, it may be important in
      immunorecognition and immunosuppression. However, excessive interleukin-4
      production may contribute to the pathophysiology of preeclampsia.

PMID- 8748254
TI  - Mycobacterium bovis BCG-induced Th1 type CD4+ suppressor T cells act by
      suppressing IL-2 production and IL-2 receptor expression.
AB  - Induction of suppressor cells has been hypothesized to explain the variability in
      the efficacy of Mycobacterium bovis BCG vaccination against mycobacterial
      diseases. In this study, we induced suppressor T cells by in vitro stimulation of
      peripheral blood mononuclear cells obtained from BCG-vaccinated healthy subjects.
      These suppressor T cells were CD4+ and did not affect interleukin-1 production by
      adherent cells in response to BCG. However, they suppressed interleukin-2 (IL-2)
      production and IL-2 receptor expression by the responding cells. Exogenous
      addition of IL-2 could partially restore the responsiveness of the indicator
      cells. To further characterize the cells responsible for suppression, T cell
      clones were established by limiting dilution. All the established T cell clones
      expressed CD4 marker, proliferated in response to BCG, were cytotoxic for antigen
      presenting cells, and suppressed the antigen-induced proliferation of the
      indicator cells. Both suppression and cytotoxicity were not mediated by soluble
      factors but required cell-to-cell contact and were HLA-class II restricted. These
      results suggest that preferential killing of antigen-presenting cells by CD4+ T
      cells may be responsible for in vitro observed suppression in our system.

PMID- 8748255
TI  - Controlling the production of interleukin-1 and tumor necrosis factor in disease.
AB  - Interleukin 1 (IL-1), either IL-1 alpha or IL-1 beta, and tumor necrosis factor
      alpha (TNF-alpha) are primarily inflammatory cytokines. The most studied drugs
      that suppress the production of IL-1 and TNF are corticosteroids, which inhibit
      the transcription of IL-1, TNF, and other cytokines. Nonsteroidal compounds that
      are cyclooxygenase-lipoxygenase inhibitors are called dual inhibitors. Other
      agents that suppress IL-1 and TNF are termed cytokine-suppressing
      antiinflammatory drugs (CSAIDs). The mechanism by which CSAIDs act appears to be
      through their ability to bind a mitogen activating protein (MAP) kinase that is
      needed for translation of cytokine mRNAs. The importance of lipoxygenase products
      in the production of IL-1 has been shown. IL-4, IL-10, and IL-3 suppress gene
      expression and synthesis of IL-1 and TNF. We carried out a randomized, double
      blind, placebo-controlled trial in healthy human volunteers using a single
      intravenous injection of IL-10. These studies indicate that IL-10 may be useful
      for suppressing inflammatory cytokine production in a variety of diseases.

PMID- 8748256
TI  - Cytokine production and cytotoxicity mediated by CD4+ T cells from healthy
      subjects vaccinated with Mycobacterium bovis BCG and from pulmonary tuberculosis
      patients.
AB  - In tuberculosis, T cells are responsible for protection but also the pathology
      caused by inflammatory responses. Most T cells activated in response to
      Mycobacterium tuberculosis express the CD4 phenotype, and are divided into Th1
      and Th2 subsets depending on the types of cytokines produced. Th1 cells protect
      against most intracellular infections including tuberculosis. To study the Th1
      and Th2 profiles against M. tuberculosis antigens, we established CD4+ T cell
      clones from the peripheral blood mononuclear cells of healthy subjects vaccinated
      with Mycobacterium bovis BCG and of pulmonary tuberculosis patients. When tested
      for cytokine production in response to mycobacterial antigens and defined
      epitopes (i.e., whole killed M. tuberculosis, a 65-kDa heat shock protein, and
      synthetic peptides) the T cell clones produced cytokines typical of Th1 cells:
      interleukin 2, interferon-gamma, and granulocyte-macrophage colony-stimulating
      factor. The same T cells also had cytotoxic activity against antigen-pulsed
      macrophages. We propose that activation of macrophages by interferon-gamma and
      killing of the pathogen-laden macrophages by cytotoxic T cells may contribute to
      protection. However, the same mechanisms may also activate the release of soluble
      mediators responsible for inflammatory responses seen in tuberculosis granulomas.

PMID- 8748257
TI  - Strategies for potential manipulation of anorexia during acute and chronic
      disease.
AB  - Acute and chronic pathologic processes and immunotherapy in humans are frequently
      accompanied by anorexia and other neurologic manifestations of disease. Various
      signals (including cytokines such as immunomodulators) are responsible for
      anorexia during disease or immunotherapy. Anorexia during disease can be
      beneficial or deleterious to an organism depending on the timing and duration.
      For example, a restriction in the intake of micronutrients and macronutrients may
      be part of the biological roles of the temporal anorexia that accompanies
      infection. However, diseases with long-term anorexia may be associated with
      cachexia. Present research on anorexia focuses on elucidating the immunochemical
      and neuronal mechanisms that contribute to anorexia and on developing potential
      interventions including the following: 1) nutritional substrates; 2) monoclonal
      antibodies, receptor antagonists, soluble receptors, and other cytokine
      (including endogenous) inhibitors; 3) glucocorticoids and other steroids; 4)
      nonsteroidal antiinflammatory agents; 5) neuropeptide inhibitors of cytokine
      action; and 6) antisense strategies.

PMID- 8748258
TI  - Nutritionally induced retinal degeneration in rats.
AB  - Nondystrophic RCS rdy+ rats were fed a vitamin E-deficient diet for a period of 3
      mo. Light and electron microscopic examination revealed degenerative alterations
      in retinal tissue in the form of a reduction in the thickness of the outer
      nuclear layer, shortening of the photoreceptor outer segments, and extreme
      thinning of the pigment epithelial cells, including a reduction in the number of
      cell organelles. These changes may be a result of increased lipid peroxidation
      activity in the retina, because vitamin E is known to have a protective
      antioxidant effect in many tissues. Some of the alterations are similar to those
      found in hereditary retinal dystrophies.

PMID- 8748259
TI  - Oral selenium supplementation in rats reduces cardiac toxicity of adriamycin
      during ischemia and reperfusion.
AB  - The aim of the present study was to assess whether an 8-wk oral selenium
      supplementation (standard food enriched with 2500 micrograms Se/kg) in rats might
      prevent the cardiotoxicity of adriamycin (ADR) treatment. ADR was administered at
      a dose of 2.5 mg/kg body wt intraperitoneally twice weekly for 3 wk. One week
      after the end of ADR treatment, rats (n = 10 per group) were killed and their
      hearts were perfused on a Langendorff mode and subjected to a 30-min period of
      low-flow ischemia (residual flow = 0.1 ml/min) followed by reperfusion (15 min).
      The results were as follows: 1) selenium supplementation significantly increased
      the activity of cardiac mitochondrial glutathione peroxidase (GPx) in ADR-treated
      rats (control: 206 +/- 17.4 IU/g protein; Se: 277 +/- 24.5 IU/g protein, p <
      0.05); 2) selenium supplementation reduced myocardial malondialdehyde content in
      ADR-treated rats (control: 1220 +/- 49.1 nmol/g protein; Se: 1010 +/- 75.9 nmol/g
      protein; p < 0.05); and 3) ADR treatment significantly increased the degree of
      reperfusion-induced structural alterations to sarcomeres compared to untreated
      hearts. Again, this phenomenon was abolished by selenium supplementation. In
      conclusion, this study demonstrates that selenium supplementation is able to
      limit ADR cardiotoxicity in isolated rat hearts submitted to a sequence of
      ischemia/reperfusion.

PMID- 8748260
TI  - Serum IgG and IgM responses to sheep red blood cells (SRBC) in weaned calves fed
      milk supplemented with Zn and Cu.
AB  - Because ruminants have a syndesmochorial placenta, the neonates are
      agammaglobinaemic and prone to morbidity and mortality from opportunistic
      infections. Only temporary benefit in passive immunity transfer from mother to
      offspring is derived from feeding colostrum to neonates. The serum immunoglobulin
      (Ig) G and IgM responses to challenges with sheep red blood cells (SRBC) were
      investigated in calves fed milk supplemented with zinc, copper, or both. Twenty
      crossbred calves, weaned on day 5, were divided into four equal groups and fed
      for 75 d. Group T1 was fed milk alone; group T2 was fed milk supplemented with 25
      ppm Cu; group T3 was fed milk supplemented with 100 ppm Zn; and group T4 was fed
      milk supplemented with 25 ppm Cu and 100 ppm Zn. The antigenic challenges with
      SRBC were made on days 35 and 65. Serum IgG and IgM levels were measured at day
      30 and at 2-wk intervals thereafter in collected blood samples. Blood zinc and
      copper levels and superoxide dismutase (SOD) activity were also measured
      periodically. Higher IgG and IgM responses were observed in groups T3 and T4 (the
      zinc-supplemented groups). The responses were higher after second challenge with
      SRBC. The changes in blood copper and zinc concentrations and SOD activity were
      in accordance with the type of supplementation. The results suggested that the
      zinc-supplemented groups in particular showed a stronger humoral immune response,
      probably as a result of the beneficial effect of zinc on the interaction between
      T helper cells and B cells.

PMID- 8748261
TI  - Evolution of the serologic response to Borrelia burgdorferi in treated patients
      with culture-confirmed erythema migrans.
AB  - We investigated the appearance and evolution of immunoglobulin M (IgM) and IgG
      antibodies to Borrelia burgdorferi in 46 patients with culture-proven erythema
      migrans (EM). All patients received antimicrobial treatment and were
      prospectively evaluated for up to 1 year. A total of 257 serially collected serum
      samples were tested by commercial IgG-IgM enzyme-linked immunosorbent assay and
      separate IgM and IgG immunoblots (IBs). At the baseline, 33% of the patients had
      a positive ELISA result and 43% of the patients had a positive IgM IB result by
      using the criteria of the Centers for Disease Control and Prevention-Association
      of State and Territorial Public Health Laboratory Directors for the
      interpretation of IB results. Positive serology at the baseline and the rate of
      seroconversion correlated directly with disease duration and/or evidence of
      dissemination prior to treatment. At days 8 to 14 after the baseline, 91% of
      patients had a positive ELISA result and/or IgM IB result. Peak IgM antibody
      levels were seen at this time in patients with localized or disseminated disease.
      The most frequent IgM bands at the baseline and the peak were of 24 kDa (OspC),
      41 kDa, and 37 kDa. Although 89% of the patients developed IgG antibodies as
      determined at a follow-up examination, only 22% were positive by the IgG IB
      criteria of the Centers for Disease Control and Prevention-Association of State
      and Territorial Public Health Laboratory Directors. The persistence of antibodies
      was directly related to disease duration and/or dissemination prior to treatment.
      Since IgM antibodies to the 24- and 41-kDa antigens remained detectable for long
      periods, 38% of IgM IBs were still positive at 1 year postbaseline. IgM to
      antigens of 39, 58, 60, 66, or 93 kDa, conversely, were most often seen in sera
      obtained within 1 month postbaseline. Their presence may be of assistance in
      confirming a recent infection with B. burgdorferi in individuals living in areas
      where Lyme disease is endemic.

PMID- 8748262
TI  - Evaluation of commercial methods for determining antimicrobial susceptibility of
      Streptococcus pneumoniae.
AB  - Seven commercial systems for antimicrobial susceptibility testing of
      Streptococcus pneumoniae were evaluated by using a challenge set of 55
      pneumococcal isolates with a variety of resistance phenotypes and genotypes.
      Overall, the results produced by the Pasco and Etest methods were found to be
      acceptable for all drugs tested except for trimethoprim-sulfamethoxazole testing
      by the Etest. The Just One system for penicillin MIC testing was also judged to
      be acceptable (minor error rate, 5.5%). Although the Sensititre and MicroTech
      methods both produced 12.7% minor errors with penicillin, the Sensititre method
      classified penicillin-intermediate strains as resistant or vice versa, while four
      of MicroTech's errors were among intermediate strains that were classified as
      susceptible. The MicroMedia (minor error rate, 16.4%) and MicroScan Rapid (minor
      error rate, 63.6%) methods produced unacceptably high levels of errors when
      testing penicillin. Minor error rates for cefotaxime and ceftriaxone ranged from
      a low of 12.7% (Etest and Sensititre) to a high of 28% (MicroMedia). Error rates
      were low for erythromycin, tetracycline, and chloramphenicol by most methods with
      the exception of the MicroScan method, which had a high very major error rate for
      erythromycin (34.6%). For testing of beta-lactam drugs, the Pasco, Etest, and
      Just One tests for penicillin are the most accurate methods; the Sensititre
      method also provided acceptable results.

PMID- 8748263
TI  - Comparison of ribotyping, arbitrarily primed PCR, and pulsed-field gel
      electrophoresis for molecular typing of Listeria monocytogenes.
AB  - Fifty-one clinical isolates of Listeria monocytogenes (15 isolates from two
      outbreaks and 36 epidemiologically unrelated isolates) were typed by conventional
      serotyping, ribotyping (RT), pulsed-field gel electrophoresis (PFGE), and
      arbitrarily primed PCR (AP-PCR). Serotyping was unable to distinguish between
      related and unrelated strains of L. monocytogenes. Each of the three molecular
      methods showed excellent typeability and reproducibility. Restriction with EcoRI
      and PvuII gave 16 and 23 RT patterns, respectively. Restriction with ApaI or SmaI
      generated 22 and 26 PFGE profiles, respectively. ApaI profiles were easier to
      interpret, with 10 to 15 bands each, while SmaI profiles had 15 to 20 bands each.
      AP-PCR with two different primers yielded 29 and 31 randomly amplified
      polymorphic DNA patterns, respectively. Strains from the same outbreak shared
      concordant patterns by each of the three methods. Of the three techniques
      evaluated, RT was the least discriminating and could not distinguish between
      strains from the two outbreaks. The abilities of AP-PCR and PFGE to differentiate
      between strains were comparable. However, AP-PCR was more rapid and easier to
      perform. We conclude that the DNA profiles generated by either AP-PCR or PFGE can
      be used to differentiate outbreak strains from epidemiologically unrelated
      strains and to clearly identify unrelated strains as being distinct from one
      another. We recommend that at least two independent primers be used for AP-PCR
      typing in order to improve its discriminatory power.

PMID- 8748264
TI  - Clinical comparison of difco ESP, Wampole isolator, and Becton Dickinson Septi
      Chek aerobic blood culturing systems.
AB  - The ESP 80A aerobic blood culture of the ESP automated blood culture system
      (Difco Laboratories. Detroit, Mich.) was compared with two manual aerobic blood
      culture systems, the Isolator (Wampole Laboratories, Cranbury, N.J.) and the
      Septi-Chek (Becton Dickinson, Cockeysville, Md.) systems, for the detection of
      bloodstream microorganisms from 5,845 blood samples for culture collected from
      adult patients with suspected septicemia. The bottles were incubated for 7 days,
      and the sediment from the Isolator tube was inoculated onto solid medium and this
      medium was incubated for 72 h. A total of 609 microorganisms were recovered from
      546 blood cultures. There was no statistically significant difference in the
      total recovery of microorganisms for the ESP 80A system when compared with that
      for the Septi-Chek system (P = 0.083); however, the Isolator system recovered
      significantly more microorganisms overall than either the ESP 80A (P < 0.001) or
      the Septi-Chek (P < 0.001) system. When assessing individual probable pathogens,
      the Isolator system detected statistically significantly more Staphylococcus
      aureus and Candida spp. than either the ESP 80A or the Septi-Chek system (P <
      0.05). Similarly, the Isolator system detected statistically significantly more
      bloodstream infections (septic episodes) caused by S. aureus and Candida spp.
      than either the ESP 80A or the Septi-Chek system (P < 0.05). In blood culture
      sets which produced growth of the same probable pathogens in the ESP 80A and the
      Isolator systems, there was no statistically significant difference in the median
      times to detection for all pathogens combined (P = 0.067). However, a similar
      comparison showed the Isolator and the ESP 80A systems to have statistically
      significantly shorter median detection times for all pathogens combined (P <
      0.001) when they were independently compared with the Septi-Chek system. The ESP
      80A system had 29 (0.5%) false-positive signals. The ESP system required less
      processing time than the Isolator system and eliminates the hands-on time for the
      detection of positive cultures required by the manual systems.

PMID- 8748265
TI  - PCR monitoring of response to liposomal amphotericin B treatment of systemic
      candidiasis in neutropenic mice.
AB  - When a diagnosis of invasive candidiasis has been made, treatment with toxic
      fungicidal agents is inevitable. The crucial decision of when to stop such
      treatment is difficult to make, because cultures are often negative despite
      ongoing invasive candidiasis and can therefore not be used as a reliable
      parameter of effective therapy. In the present study, the use of PCR in
      monitoring the therapeutic efficacy of antifungal treatment with liposomal
      amphotericin B was evaluated by using neutropenic mice with systemic candidiasis.
      Blood cultures of infected mice treated with different doses of liposomal
      amphotericin B were only positive at the early onset of the infection process and
      became sterile within 3 days; this was true even with mice treated with 1 mg of
      liposomal amphotericin B per kg of body weight that experienced a relapse of
      infection 14 days later. A significant correlation between presence of Candida
      albicans in the kidneys and PCR results obtained with blood was demonstrated.
      Thus, PCR results obtained with blood samples correlated well with the
      therapeutic efficacy of antifungal treatment.

PMID- 8748266
TI  - Detection of cytomegalovirus in blood donors by PCR using the digene SHARP signal
      system assay: effects of sample preparation and detection methodology.
AB  - Cytomegalovirus (CMV) is an important cause of transfusion-associated morbidity
      and mortality; however, only 0.4 to 12% of the blood products obtained from
      seropositive blood donors transmit infection. The effects of three commercially
      available whole-blood sample preparation kits on the detection of CMV PCR
      products by a semiquantitative adaptation of the Digene SHARP Signal System Assay
      (DSSSA) in samples from volunteer blood donors was assessed. Of 101 samples from
      seropositive blood donors, CMV was detected in 0 (0%) of the samples extracted
      with a QIAamp blood kit (QIAGEN), 1 (1%) of the samples extracted with an
      Amplicor whole-blood specimen preparation kit (Roche), and 8 (8%) of the samples
      extracted with an Isoquick nucleic acid extraction kit (modified by the addition
      of carrier tRNA) (Microprobe). CMV DNA was not detected in samples from
      seronegative blood donors (n = 13). Nested PCR of selected samples confirmed the
      detection of CMV in the sane eight samples extracted with the modified Isoquick
      nucleic acid extraction kit and detected an additional nine CMV-positive samples
      (n = 50). Samples from volunteer blood donors contain low copy numbers of CMV
      DNA. PCR amplification of such specimens can result in analytical sampling
      errors, giving results similar to the variations in titers recognized during
      determinations of the 50% tissue culture infective dose. The detection of CMV in
      blood samples from volunteer blood donors by PCR is a function of sample
      preparation, amplification conditions, and detection methodology. Accurate
      assessments of the clinical utility of CMV DNA detection by nucleic acid
      amplification for blood product screening and patients will require highly
      standardized and quantitative methodology.

PMID- 8748267
TI  - Clinical comparison of isolator, Septi-Chek, nonvented tryptic soy broth, and
      direct agar plating combined with thioglycolate broth for diagnosing spontaneous
      bacterial peritonitis.
AB  - Spontaneous bacterial peritonitis is a life-threatening complication of cirrhotic
      ascites. Optimal patient management depends on the isolation of the causal
      organism from ascitic fluid. To evaluate culture techniques for the diagnosis of
      spontaneous bacterial peritonitis, we prospectively compared three blood culture
      system, the Isolator system, a lysis-centrifugation system, the Septi-Chek
      system, a biphasic culture system, and a nonvented tryptic soy broth system, all
      inoculated at the bedside, and our standard method of direct inoculation of
      specimens after transport to the laboratory onto agar plates and into
      thioglycolate broth. The results showed that the Septi-Chek and nonvented tryptic
      soy broth systems each recovered statistically significantly more pathogens than
      either the Isolator system (P = 0.0084) or the standard method (P = 0.00098). The
      Isolator system recovered more pathogens than the standard plate method, but this
      difference was not statistically significant. Both the Isolator system and the
      standard plate method recovered more contaminating microorganisms than the Septi
      Chek or nonvented tryptic soy broth system. The Isolator system required the most
      processing time compared with the processing times required by any other method.

PMID- 8748268
TI  - Comparative evaluation of several techniques for purification of Cryptosporidium
      parvum oocysts from rat feces.
AB  - Three methods of isolating Cryptosporidium parvum oocysts from rat feces were
      evaluated. Oocysts were initially isolated by sucrose density gradient
      centrifugation. They were further purified by passage through a glass bead column
      or a Percoll gradient or by dialysis. Although oocysts recovered from the glass
      bead column and by dialysis were relatively free of fecal debris, only oocysts
      recovered from the Percoll gradient were free of bacteria. Recovered oocysts
      retained their antigenicity and infectivity. The ability to effectively recover
      oocysts from rat feces suggests that the laboratory rat may be a convenient
      substitute for ruminants in the propagation and maintenance of C. parvum oocysts
      for in vitro and in vivo use.

PMID- 8748269
TI  - Discrimination of respiratory syncytial virus subgroups A and B by reverse
      transcription-PCR.
AB  - Reverse transcription (RT)-PCR with shared primers differentiating respiratory
      syncytial virus (RSV) subgroups A and B was developed for subtyping of RSV
      isolates. Results of RT-PCR were compared with those of an indirect
      immunofluorescence test using monoclonal antibodies. Viral RNA isolated from cell
      cultures infected with RSV served as a template for cDNA synthesis with random
      primers. For PCR, we used three synthetic oligonucleotides corresponding to the G
      protein mRNA sequence of subgroup A (bases 248 to 267; 3'ATGCAACAAGCCAGATCAAG),
      subgroup B (bases 314 to 333; 3'ACTCATCCAAACAACCCACA), or both (bases 511 to 530;
      3'GGWACAAARTTGAACACTTC). PCR products of RSV subgroups A and B had molecular
      sizes of 283 and 217 bp, respectively. Specific cutting sites for RSV A and B in
      amplified cDNA were demonstrated by restriction fragment analysis with four
      restriction endonucleases. Our RT-PCR assay divided 68 RSV isolates into 47
      strains of subgroup A and 21 strains of subgroup B in full agreement with
      subtyping by monoclonal antibodies. RT-PCR seems to be a good alternative to
      subtyping of RSV with monoclonal antibodies.

PMID- 8748270
TI  - Geographic, clinical, serologic, and molecular evidence of granulocytic
      ehrlichiosis, a likely zoonotic disease, in Minnesota and Wisconsin dogs.
AB  - Seventeen Minnesota and Wisconsin dogs with granulocytic ehrlichosis were
      studied. The diagnoses were made by finding ehrlichia morulae in peripheral blood
      neutrophils. Eight dogs were studied retrospectively, and nine dogs were studied
      prospectively. The medical records of all dogs were reviewed. Eighty-eight
      percent of the dogs were purebred and 76% were spayed females. The median age was
      8 years. Sixty-five percent of the cases were diagnosed in October and November.
      Fever and lethargy were the most common clinical signs. The most frequent
      laboratory findings were lymphopenia, thrombocytopenia, elevated activities of
      serum alkaline phosphatase and amylase, and hypoalbuminemia. No dogs seroreacted
      to Ehrlichia canis or Ehrlichia chaffeensis antigens, which are cross-reactive.
      Seventy-five percent of the dogs tested during the acute phase of disease and
      100% of the dogs tested during convalescence were seropositive for E. equi
      antigens. Granulocytic ehrlichial 16S rRNA gene DNAs from six dogs were amplified
      by PCR. Sequence analysis of a 919-bp sequence of the ehrlichial 16S rRNA gene
      amplified by PCR from the blood of two dogs revealed the agent to be identical to
      the agent of human granulocytic ehrlichiosis in Minnesota and Wisconsin and to be
      very similar to E. equi and Ehrlichia phagocytophila and less similar to E.
      canis, Ehrlichia ewingii, and E. chaffeensis. The geographic, clinical,
      serologic, and molecular evidence indicates that granulocytic ehrlichiosis in
      Minnesota and Wisconsin dogs is not caused by E. ewingii, but suggests that it is
      a zoonotic disease caused by an agent closely related to E. equi and that dogs
      likely contribute to the enzootic cycle and human infection.

PMID- 8748271
TI  - Simultaneous PCR detection of Haemophilus ducreyi, Treponema pallidum, and herpes
      simplex virus types 1 and 2 from genital ulcers.
AB  - A multiplex PCR (M-PCR) assay with colorimetric detection was devised for the
      simultaneous amplification of DNA targets from Haemophilus ducreyi, Treponema
      pallidum, and herpes simplex virus (HSV) types 1 and 2. By using target-specific
      oligonucleotides in a microwell format, 298 genital ulcer swab specimens
      collected in New Orleans during three intervals from 1992 through 1994 were
      evaluated. The results of the M-PCR assay were compared with the results of dark
      field microscopy and H. ducreyi culture on two different culture media. HSV
      culture results were available for 99 specimens collected during the third
      interval. Confirmatory PCR assays targeting different gene sequences for each of
      the three organisms were used to validate the M-PCR results. Specimens were
      resolved as positive for the determination of sensitivity if the reference
      diagnostic test was positive or if the results of both the M-PCR and the
      confirmatory PCR were positive. The resolved sensitivities of M-PCR for HSV, H.
      ducreyi, and T. pallidum were 100, 98.4, and 91%, respectively. The resolved
      sensitivities of HSV culture, H. ducreyi culture, and dark-field microscopy were
      71.8, 74.2, and 81%, respectively. These results indicate that the M-PCR assay is
      more sensitive than standard diagnostic tests for the detection of HSV, H.
      ducreyi, and T. pallidum from genital ulcers.

PMID- 8748272
TI  - Genetic diversity among Mycobacterium avium complex AccuProbe-positive isolates.
AB  - The partial 32-kDa-protein gene sequences of 22 Mycobacterium avium complex (MAC)
      clinical isolates that were positive by the AccuProbe MAC probe only (not by the
      M. avium or M. intracellulare probe) were determined. The obtained nucleotide
      sequences were compared with the published sequences for M. tuberculosis, M.
      avium, and M. intracellulare by a sequence analysis program. There was a wide
      range of genetic diversity among the strains studied. Most of them (16 of 22) had
      sequences similar but not identical to those of M. avium and M. intracellulare.
      These strains were considered to be true MAC strains. Five strains had sequences
      in the category of the novel MAIX sequence, which was very different from the
      sequences of other mycobacteria analyzed thus far. In addition to these strains,
      one isolate had a sequence that differed greatly from the reference sequences.
      These results support previous findings showing that the MAC probably contains
      several additional species. Our results also suggest that the MAC AccuProbe may
      react with strains that do not belong to the MAC.

PMID- 8748273
TI  - Application of CHROMagar Candida for rapid screening of clinical specimens for
      Candida albicans, Candida tropicalis, Candida krusei, and Candida (Torulopsis)
      glabrata.
AB  - CHROMagar Candida is a new differential culture medium that allows selective
      isolation of yeasts and simultaneously identifies colonies of Candida albicans,
      C. tropicalis, and C. krusei. We evaluated the use of this medium with 316 yeast
      isolates including 247 isolated directly on CHROMagar from clinical material.
      Over 95% of stock and clinical isolates of C. albicans, C. tropicalis, and C.
      krusei were correctly identified on the basis of colony morphology and
      pigmentation on CHROMagar. Additionally, CHROMagar also allowed the
      identification of C. (Torulopsis) glabrata at a similar level of accuracy. The
      overall agreement between two observers in reading the CHROMagar plates was 95%.
      Growth of Candida sp. isolates on CHROMagar had no adverse effect on antifungal
      MICs or Vitek identification results. In parallel, cultures of 548 stool and
      rectal swab specimens set up on CHROMagar and Sabouraud glucose agar (SGA) were
      positive in 234 instances. CHROMagar was positive and SGA was negative for 11
      specimens, and CHROMagar was negative and SGA was positive for 18 specimens. A
      single yeast species was isolated on both media from 162 specimens, and in 146
      (90%) of these specimens the same species was detected on both CHROMagar and SGA.
      A total of 43 of the 234 positive cultures contained mixtures of yeast species.
      Twenty (47%) of these mixed cultures were detected only on CHROMagar. CHROMagar
      is extremely useful in making a rapid presumptive identification of common yeast
      species. This capability plus the ability to detect mixed cultures of Candida
      spp. promises to improve and streamline the work flow in the mycology and
      clinical microbiology laboratory.

PMID- 8748274
TI  - Rapid identification of Campylobacter species by restriction fragment length
      polymorphism analysis of a PCR-amplified fragment of the gene coding for 16S
      rRNA.
AB  - Restriction fragment length polymorphism analysis of a PCR-amplified DNA fragment
      of the gene coding for 16S rRNA was performed on 148 previously characterized
      strains of Campylobacter, Helicobacter, Arcobacter, and Wolinella succinogenes
      and 13 Campylobacter-like isolates. These strains included clinical, animal, and
      environmental isolates. PCR amplification generated a 283-bp fragment from all
      species. The amplicon from each strain was digested with six restriction
      endonucleases (AccI, AvaI, DdeI, HaeIII, HpaII, XhoI). DdeI was useful for the
      initial grouping of the strains. Additional discrimination within the different
      DdeI groups was obtained with AccI, HaeIII, HpaII, and XhoI digestions. The PCR
      restriction fragment length polymorphism analysis allowed for the discrimination
      of members of the genus Campylobacter from members of closely related genera and
      discrimination between Campylobacter species. The proposed method is simple and
      rapid and can be useful for the routine identification of Campylobacter-like
      organisms in clinical or epidemiologic studies.

PMID- 8748275
TI  - Epidemiological typing of Flavimonas oryzihabitans by PCR and pulsed-field gel
      electrophoresis.
AB  - Flavimonas oryzihabitans has emerged as a potential nosocomial pathogen in recent
      years. The typing method for characterization of this species has never been
      reported before. Pulsed-field gel electrophoresis (PFGE) and enterobacterial
      repetitive intergenic consensus (ERIC)-based PCR were used to generate DNA
      fingerprints for 14F. oryzihabitans isolates obtained from eight episodes of
      nosocomial infections during a 2-year period. Both techniques successfully
      classified these clinical isolates into eight distinct genotypes, thus indicating
      that all of these episodes of infections were independent. In contrast, repeated
      isolates from the same patient were assigned to identical genotypes. The
      reproducibility of both techniques was good. Therefore, we conclude that both
      PFGE and ERIC-PCR have comparable reproducible and discriminatory powers for the
      typing of F. oryzihabitans and may be useful for clarifying the epidemiology of
      this species; however, ERIC-PCR has the advantages of both speed and simplicity.

PMID- 8748276
TI  - Comparison of infectivities of six tick-derived isolates of Borrelia burgdorferi
      for rodents and ticks.
AB  - The infectivity and dissemination to the skin of six isolates of Borrelia
      burgdorferi were evaluated by inoculating them into groups of deer mice
      (Peromyscus maniculatus), hamsters, and Swiss Webster mice. Rodent infection was
      assayed by culture of ear punch biopsy specimens taken at 4, 8, and 12 weeks
      postinoculation (p.i.). Spirochetes were detected in biopsy specimens from
      individuals of all three host species that had been inoculated with four isolates
      (CA3, CA4, CA7, and CA8). Ear punch biopsy specimens taken from Swiss Webster
      mice at 12 weeks p.i. yielded an additional reisolate (CA2), even though these
      animals did not seroconvert. The remaining isolate (CA9) was not recovered from
      any host. However, two deer mice and all hamsters and Swiss Webster mice
      inoculated with CA9 seroconverted. All six isolates were of low infectivity to
      ticks when inoculated intramuscularly into hosts. Only 4 (1.6%) of 250 Ixodes
      pacificus larvae acquired and transstadially maintained infection from hosts
      inoculated intramuscularly. Infectivity of three isolates for ticks also was
      tested in Swiss Webster mice injected intradermally. The mean prevalences of
      infection in xenodiagnostic ticks fed on these mice at 4 weeks p.i. were 47.9,
      1.2, and 2.2% for isolates CA4, CA7, and CA8, respectively. The mean prevalences
      of infection for ticks fed on the same mice at 12 weeks p.i. were 36.4, 11.8, and
      20.4%, respectively. Such differences in the infectivity and rate of
      dissemination of individual isolates of B. burgdorferi should be considered
      during studies of reservoir and vector competence.

PMID- 8748277
TI  - Outbreak of TEM-24-producing Enterobacter aerogenes in an intensive care unit and
      dissemination of the extended-spectrum beta-lactamase to other members of the
      family enterobacteriaceae.
AB  - We report an outbreak of Enterobacter aerogenes in an intensive care unit (ICU)
      and two medicine departments that produced the extended-spectrum beta-lactamase
      TEM-24, which was difficult to detect by disk agar diffusion. The strains were
      compared by DNA restriction fragment length polymorphism after pulsed-field gel
      electrophoresis following cleavage with XbaI. This typing method indicated that a
      single strain, first isolated in the ICU, spread throughout the other medical
      departments as a result of patient transfer. We also observed the transfer in
      vivo of the plasmid encoding TEM-24 from the strain of Enterobacter aerogenes to
      different strains of Escherichia coli and Citrobacter freundii in the ICU. It
      therefore appears that the epidemic involved results from two events:
      dissemination of one strain of Enterobacter aerogenes and dissemination of the
      plasmid encoding TEM-24 among various members of the family Enterobacteriaceae.

PMID- 8748278
TI  - Significance of indeterminate third-generation hepatitis C virus recombinant
      immunoblot assay.
AB  - Indeterminate hepatitis C virus (HCV) third-generation recombinant immunoblot
      assay (RIBA3.0; Ortho Diagnostic Systems) patterns were arbitrarily defined by
      the manufacturer as the detection of only one antibody out of the four that were
      sought, namely, c100 (NS4 encoded), c22 (core encoded), c33c (NS3 encoded), and
      NS5 (NS5 encoded). The aims of the present study were (i) to determine the
      prevalence of indeterminate RIBA3.0 patterns in patients consecutively tested for
      anti-HCV antibodies in a university hospital; (ii) to evaluate the significance
      of these patterns in terms of viral replication, liver disease, and risk factors
      for HCV; and (iii) to get an insight into the mechanism underlying this peculiar
      immune response. Among 3,074 serum samples consecutively tested for anti-HCV
      antibodies, 588 were found to be positive by screening assays. Fifty-nine of them
      (10%) were RIBA3.0 indeterminate and were compared with 59 RIBA3.0-positive ones.
      Thirty-one RIBA3.0-indeterminate and 53 RIBA3.0-positive serum samples were HCV
      RNA positive by PCR (53 versus 90%; P < 10(-6). RIBA3.0-indeterminate and RIBA
      3.0-positive patients with positive PCR results were not significantly different
      for the prevalence of risk factors for HCV infection and elevated serum alanine
      aminotransferase activities. Immunosuppression, attributable to coexisting human
      immunodeficiency virus infection, organ transplantation, or the administration of
      immunosuppressive drugs, was significantly more frequent in PCR-positive, RIBA3.0
      indeterminate patients than in PCR-negative, RIBA3.0 indeterminate patients (P <
      0.001) and PCR-positive patients with a positive RIBA3.0 result (P < 0.01). The
      distribution of HCV genotypes did not differ significantly between HCV RNA
      positive patients with indeterminate or positive RIBA3.0 results. In conclusion,
      the prevalence of indeterminate RIBA3.0 patterns in virology laboratories is
      about 10%; in about half of these patients HCV replication is detected by PCR;
      the main factor responsible for indeterminate RIBA3.0 patterns could be
      immunosuppression, whereas HCV genotypes do not seem to play major role.

PMID- 8748279
TI  - Growth inhibition of Mycobacterium tuberculosis by polyoxyethylene stearate
      present in the BACTEC pyrazinamide susceptibility test.
AB  - We have previously found that approximately 3.5% of 428 clinical isolates of
      Mycobacterium tuberculosis yield uninterpretable results in the BACTEC
      pyrazinamide (PZA) susceptibility test system, because of inadequate growth. We
      tested the hypothesis that polyoxyethylene stearate (POES), the ingredient of the
      reconstituting fluid for the test, was the cause of this growth inhibition. A
      total of 15 isolates known for their previously uninterpretable results and 100
      randomly chosen clinical isolates were tested in parallel both with and without
      POES. Repeat testing of the isolates with previously uninterpretable results
      yielded results in the presence of POES in only seven (47%). In the absence of
      POES, all gave interpretable results but one such result showed false resistance.
      For the other 100 clinical isolates, interpretable results were obtained with and
      without POES, but growth was enhanced in the absence of POES, especially in the
      PZA-susceptible strains. This was evidenced by a decreased time to attain a
      growth index of 200 in the control vial (4.9 days without POES versus 5.8 days
      with POES; P < 0.001) and a higher mean growth index ratio on the day of
      interpretation of the test (7.4% without POES versus 2.2% with POES; P < 0.001).
      However, the enhanced growth without POES led to 20 susceptible strains being
      misinterpreted as either resistant or borderline. We suggest that isolates of M.
      tuberculosis which yield uninterpretable results in the BACTEC PZA test system
      should be retested both with and without POES. If interpretable results
      indicating PZA resistance are obtained only in the absence of POES, the result
      should be confirmed by a pyrazinamidase assay or by the conventional proportion
      method. Routine omission of POES from the BACTEC test for all clinical strains is
      discouraged because of the unacceptably high false-resistance rates.

PMID- 8748280
TI  - Molecular typing by random amplification of polymorphic DNA and M13 southern
      hybridization of related paired isolates of Aspergillus fumigatus.
AB  - Three forms of DNA-based typing procedures for Aspergillus fumigatus isolates
      have been developed over the last five years. The procedures are random
      amplification of polymorphic DNA (RAPD), restriction fragment length polymorphism
      (RFLP) detection, and Southern hybridizations with various repetitive sequence
      based probes. Using two of these procedures, we compared 16 selected isolates,
      grouped into eight pairs on the basis of epidemiology or previously assigned RFLP
      types. RAPD with four primers (R108, RC08, 2, and 4), including three previously
      used with A. fumigatus, showed that one primer, R108, gave the best
      discrimination (8 types). Southern hybridization of total genomic DNA digested
      with HindIII and probed with the total bacteriophage M13 genome resulted in the
      highest overall level of discrimination. Combination of the RAPD and Southern
      hybridization with the previously assigned RFLP types discriminated 10 isolates
      of 16. Isolates closely linked epidemiologically could not be distinguished from
      each other. In addition, three pairs of isolates previously unlinked by
      epidemiology had the same overall types. Two pairs were obtained from the same
      hospital within 2 years of each other, whereas the third pair were isolated from
      California and Germany. A full understanding of the epidemiology and ecology of
      A. fumigatus requires multiple discriminatory typing procedures.

PMID- 8748281
TI  - Comparison of three commercially available enzyme-linked immunosorbent assays and
      biopsy-dependent diagnosis for detecting Helicobacter pylori infection.
AB  - We evaluated the performance of three enzyme-linked immunosorbent assays (ELISAs)
      in detecting serum immunoglobulin G (IgG) and IgA antibodies to Helicobacter
      pylori; two were new ones from Pyloriset (Pyloriset EIA-G update and Pyloriset
      EIA-A update; Orion Diagnostica, Espoo, Finland), and the third was the Malakit
      EIA-G (Biolab, Limal, Belgium). Serum samples from 154 dyspeptic patients were
      collected. As a reference method, multiple biopsy specimens from different
      anatomical areas of the stomach were obtained by endoscopy and were analyzed by
      culture and/or histology and direct urease testing. Accordingly, 126 patients
      (82%) were found to be H. pylori positive and 28 patients (18%) were found to be
      H. pylori negative. To validate serology as a predictor of H. pylori infection,
      sensitivity, specificity, positive and negative predictive values, and accuracy
      of the assays were calculated against the H. pylori status as determined by the
      reference method. The corresponding data for the different ELISAs were 100%, 79%,
      95%, 100%, and 96% for the Pyloriset ELA-G update, 81%, 89%, 97%, 52%, and 82%
      for the Pyloriset EIA-A update, and 87%, 86%, 96%, 60%, and 87% for the Malakit
      EIA-G, respectively. We conclude that the Pyloriset EIA-G update is a reliable
      and accurate test and that because of its 100% sensitivity, conjunctional IgA
      testing is not necessary. Its 100% negative predictive value makes it a very
      useful screening test. For purposes of excluding infection with H. pylori, the
      performance of the Malakit EIA-G is moderate but can be improved by conjunctional
      IgA testing. The Pyloriset EIA-A update can be useful as such a conjunctional
      test.

PMID- 8748282
TI  - Molecular technique for rapid identification of mycobacteria.
AB  - Identification of mycobacteria through conventional microbiological methods is
      cumbersome and time-consuming. Recently we have developed a novel bacterial
      identification method to accurately and rapidly identify different mycobacteria
      directly from water and clinical isolates. The method utilizes the PCR to amplify
      a portion of the small subunit rRNA from mycobacteria. The 5' PCR primer has a
      fluorescent label to allow detection of the amplified product. The PCR product is
      digested with restriction endonucleases, and an automated DNA sequencer is
      employed to determine the size of the labeled restriction fragments. Since the
      PCR product is labeled only at the 5' end, the analysis identifies only the
      restriction fragment proximal to the 5' end. Each mycobacterial species has a
      unique 5' restriction fragment length for each specific endonuclease. However,
      frequently the 5' restriction fragments from different species have similar or
      identical lengths for a given endonuclease. A set of judiciously chosen
      restriction enzymes produces a unique set of fragments for each species,
      providing us with an identification signature. Using this method, we produced a
      library of 5' restriction fragment sizes corresponding to different clinically
      important mycobacteria. We have characterized mycobacterial isolates which had
      been previously identified by biochemical test and/or nucleic acid probes. An
      analysis of these data demonstrates that this protocol is effective in
      identifying 13 different mycobacterial species accurately. This protocol has the
      potential of rapidly (less than 36 h) identifying mycobacterial species directly
      from clinical specimens. In addition, this protocol is accurate, sensitive, and
      capable of identifying multiple organisms in a single sample.

PMID- 8748283
TI  - Novel method for rapid identification of Nocardia species by detection of
      preformed enzymes.
AB  - The purpose of the present study was to devise a method for the identification of
      Nocardia species that is more technically simple, accurate, and rapid than
      current standard methods of identification. We focused on a commercial bacteria
      identification system that contained chromogenic test substrates. Two MicroScan
      products were selected for use in the study on the basis of their content of
      chromogenic and conventional substrates. They were the Rapid Anaerobe
      Identification and the HNID panels. A total of 85 strains of Nocardia
      representing five species were used in the study. All isolates were identified as
      Nocardia species by the use of standard methods. The beta-naphthylamide-labeled
      substrate L-pyrrolidonyl-beta-naphthylamide (PYR), the nitrophenyl-labeled
      substrate p-nitrophenyl-alpha-D-mannopyranoside (MNP), and indoxyl phosphate were
      found to be useful for identification purposes. N. farcinica and N. nova were the
      only species positive for PYR, whereas N. brasiliensis was the only species that
      hydrolyzed MNP. All strains of N. brasiliensis, N. otitidiscavarium, and N.
      farcinica were positive for indoxyl phosphate, whereas strains of N. nova and N.
      asteroides sensu stricto were always negative. Agreement between the standard and
      enzymatic identification methods was 100%. In summary, detection of preformed
      enzymes appears to be a simple and reproducible method for the identification of
      Nocardia spp.

PMID- 8748284
TI  - Biochemical investigations of biogroups and subspecies of Morganella morganii.
AB  - We determined the subspecies and biogroup designations for 73 strains of
      Morganella morganii principally recovered from routine clinical specimens. On the
      basis of trehalose fermentation, 90% of all strains were identified as M.
      morganii subsp. morganii (trehalose negative), while the remaining 10% were
      designated M. morganii subsp. sibonii (trehalose positive). Using three tests
      (ornithine decarboxylase [ODC] and lysine decarboxylase [LDC] activities and
      susceptibility to tetracycline), we determined the biogroup designations for
      these 73 strains. Four of the seven recognized biogroups within the genus
      Morganella were found in the study, with biogroup A (ODC positive [ODC+], LDC
      negative [LDC-]) predominating (78%); all M. morganii subsp. sibonii strains were
      found to belong to biogroup G (ODC+, LDC-). Rapid glycerol fermentation (24 h)
      was linked to nonmotility and biogroup B strains (ODC+, LDC+). LDC activity but
      not tetracycline resistance appeared to be associated with the possession of a 40
      to 45-MDa plasmid. The use of three commercial systems (API ZYM, API 50 CH, and
      Biolog GN) failed to detect any new biochemical tests useful for subspecies
      identification, with the possible exception of L-phenylalanine utilization as a
      sole carbon source in the Biolog GN system. No Morganella strain was found to
      invade either HEp-2 or Vero cell lines, but four of seven M. morganii subsp.
      morganii strains were cytotoxic on sheets of both cells. This cytotoxic activity
      appeared to correlate with the rapid expression of beta-hemolytic activity.

PMID- 8748285
TI  - Outbreak of group A streptococci in a burn center: use of pheno- and genotypic
      procedures for strain tracking.
AB  - In a burn center, an outbreak of group A streptococci (GAS) colonizations
      involving 13 patients and two staff members occurred. Adverse events due to GAS,
      loss of skin graft after initial take (secondary loss) and partial take, occurred
      in patients who underwent surgery before the colonization was detected. GAS
      isolates from nine patients and one staff member were stored and subsequently
      pheno- and genotyped by T serotyping, gas chromatography, M genotyping, and
      random amplified polymorphic DNA typing. The outbreak was caused by two types of
      GAS, identified as T4/28-M48 and T13-M77 by T serotyping and M genotyping. Random
      amplified polymorphic DNA typing and gas chromatography distinguished both
      clusters accurately. One subcluster indicated by gas chromatography could be
      linked to the acquisition of GAS from a roommate. The T13-M77 cluster was
      characterized by rapid spread through the center compared with the T4/28-M48
      cluster. One patient contracted the T13-M77 strain while in protective isolation,
      indicating a role for staff members in the transmission. Our standard GAS control
      policy, consisting of twice weekly screening of all burned patients and immediate
      isolation and treatment, proved efficacious in preventing further spread of GAS.
      Reporting by staff members of signs and symptoms compatible with GAS infection
      was reenforced.

PMID- 8748287
TI  - Comparative evaluation of BACTEC aerobic Plus/F and Septi-Chek Release blood
      culture media.
AB  - The BACTEC 9240 (Becton Dickinson, Sparks, Md.) automated blood culture system is
      based on the continuous monitoring of CO2 production by means of a fluorescent
      sensor attached to the bottom of culture vials. We compared the performance of
      the BACTEC aerobic Plus/F medium to that of the Septi-Chek Release medium (Becton
      Dickinson, Sparks, Md.), a manual biphasic blood culture system. Sets consisting
      of BACTEC aerobic Plus/F and Septi-Chek Release vials inoculated with similar
      volumes (7 +/- 2 ml) were evaluated. In the laboratory, systems were equipped and
      analyzed according to the manufacturer's recommendations. The BACTEC and Septi
      Chek vials were incubated at 35 degrees C for 5 days. A total of 6,116 compliant
      sets were obtained from 1,972 adult patients (3.1 cultures per patient). Of
      these, 731 (12%) were culture positive, including 612 (10%) that yielded at least
      one pathogen, and 143 (2%) were considered to be contaminated. Of the 672
      pathogenic organisms detected, 524 were isolated from the BACTEC aerobic Plus/F
      medium and 574 were isolated from the Septi-Chek Release medium, 428 organisms
      grew in both media, 96 organisms grew only in the BACTEC aerobic Plus/F medium,
      and 146 organisms grew only in the Septi-Chek Release medium (P = 0.001).
      Haemophilus spp. were isolated more often (P = 0.03) from the BACTEC aerobic
      Plus/F medium; however, more Streptococcus anginosus organisms (P = 0.02),
      members of the Enterobacteriaceae family (P < 0.03), and gram-negative anaerobes
      (P = 0.03) were isolated from the Septi-Chek Release medium. Pathogenic organisms
      were detected significantly earlier (P < 0.0001) with the BACTEC aerobic Plus/F
      medium in conjunction with the BACTEC 9240 instrument than with the Septi-Chek
      Release medium.

PMID- 8748286
TI  - Antigenic properties and diagnostic potential of puumala virus nucleocapsid
      protein expressed in insect cells.
AB  - Puumala virus (PUU) is a member of the genus Hantavirus in the family
      Bunyaviridae and the causative agent of nephropathia epidemica, a European form
      of hemorrhagic fever with renal syndrome. Sera of nephropathia epidemica patients
      react specifically with PUU nucleocapsid (N) protein. In order to safely provide
      large quantities of antigen for diagnostic purposes, PUU Sotkamo strain N protein
      was expressed by using the baculovirus system in Sf9 insect cells to up to 30 to
      50% of the total cellular protein. The recombinant N protein (bac-PUU-N) was
      solubilized with 6 M urea, dialyzed, and purified by anion-exchange liquid
      chromatography. In an immunoglobulin M mu-capture assay purified and unpurified
      bac-PUU-N antigen showed identical results compared with the results of a similar
      assay based on native PUU antigen grown in Vero E6 cells. An immunoglobulin G
      monoclonal antibody-capture assay based on unpurified bac-PUU-N also showed
      results identical to those of an assay with native PUU-N antigen. Moreover, a
      panel of monoclonal antibodies reactive with eight different epitopes showed
      identical reactivity patterns with both natural and bac-PUU-N antigen, while two
      epitopes in PUU-N expressed as a fusion protein in Escherichia coli were not
      recognized. Puumala hantavirus N protein expressed by the baculovirus system
      offers a safe and inexpensive source of specific antigen for large-scale
      diagnostic and seroepidemiological purposes.

PMID- 8748288
TI  - Evaluation of Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test and
      Roche PCR-microwell plate hybridization method (AMPLICOR MYCOBACTERIUM) for
      direct detection of mycobacteria.
AB  - We evaluated the clinical utility of an rRNA amplification-based Gen-Probe
      Amplified Mycobacterium Tuberculosis Direct Test (AMTD) system and a PCR-based
      Roche AMPLICOR MYCOBACTERIUM system for direct detection of Mycobacterium
      tuberculosis, M. avium, and M. intracellulare. Of the 422 sputum samples from 170
      patients, 137 (121 of M. tuberculosis, 14 of M. avium-M. intracellulare complex
      [MAC], 2 of mycobacterium other than M. tuberculosis or MAC) were culture
      positive with the Septi-Chek AFB system. One sample of a contaminated culture
      results was excluded for further analyses. The AMTD system detected all of the
      121 samples which grew M. tuberculosis (sensitivity, 100%). Of the 284 culture
      negative samples, 28 were positive by this system (specificity, 90.1%). After
      resolution of the discrepant samples, based on a positive history for culture of
      the patient, the specificity of this system increased to 99.3%. On the other
      hand, the AMPLICOR system gave a positive result for 132 out of the 135 culture
      positive samples for M. tuberculosis or MAC (sensitivity, 97.8%). Of the 284
      culture-negative samples, 37 were positive by this system (specificity, 87.0%).
      The specificity for this system after resolution of the discrepant samples
      increased to 98.9%. The agreement between the results from the AMTD system and
      the AMPLICOR system was 98.7%. Both of the systems are highly sensitive and
      specific for detecting M. tuberculosis and/or MAC directly from sputum samples
      within hours, and they should be recommended for routine use in the clinical
      microbiology laboratory.

PMID- 8748289
TI  - Evaluation of Roche Amplicor PCR assay for Mycobacterium tuberculosis.
AB  - The Roche Amplicor Mycobacterium tuberculosis PCR test (RMtb-PCR) was compared
      with mycobacterial culture, with the BACTEC 460 system and inoculation on
      Lowenstein-Jensen media. Results were interpreted with an adjusted "gold
      standard" incorporating clinical diagnosis. A total of 1,480 clinical specimens
      from 1,155 patients, including tissues and fluids, as well as 141 specimens which
      demonstrated a positive growth index on the BACTEC 460 system were assessed. The
      sensitivity, specificity, and positive and negative predictive values of RMtb-PCR
      compared with the adjusted gold standard for clinical specimens were 79, 99, 93,
      and 98%, respectively. In smear-positive specimens, the sensitivity of RMtb-PCR
      was 98% versus 53% for smear-negative specimens. When RMtb-PCR was performed two
      times per week, PCR results were available an average of 21 days before the
      culture results. For specimens demonstrating a positive growth index on the
      BACTEC 460 system, RMtb-PCR had a sensitivity and specificity of 98 and 100%,
      respectively. This study demonstrates the value of a commercial nucleic acid
      amplification kit for rapid diagnosis of M. tuberculosis, particularly in smear
      positive specimens or BACTEC culture-positive specimens.

PMID- 8748290
TI  - Diagnosis of viral respiratory tract infections in children by using a reverse
      transcription-PCR panel.
AB  - Reverse transcription-PCR (RT-PCR) is a sensitive method for detection of RNA
      virus nucleic acid sequences in clinical respiratory specimens. Previous studies
      have focused on RT-PCR for a single virus, but this approach is limited by the
      inability to establish a specific etiology when the RT-PCR result is negative and
      by the inability to document simultaneous infections involving more than one
      virus. The purpose of this study was to apply a panel of RT-PCR protocols for
      respiratory syncytial virus, parainfluenza virus, and picornaviruses to
      respiratory specimens from 80 children suspected to have acute viral respiratory
      tract infections and to correlate RT-PCR results with viral culture results and
      clinical diagnosis. In comparison with viral culture, the RT-PCR panel had a
      sensitivity of over 94% and showed evidence of simultaneous infections in a
      significantly greater proportion of specimens (20.0% versus 3.8%; P < 0.002). For
      specimens in which no viruses were detected by culture, the proportion of
      specimens with positive picornavirus RT-PCR results was significantly greater
      than the proportion of specimens with positive respiratory syncytial virus or
      parainfluenza virus RT-PCR results (P < 0.001). There were no statistically
      significant associations between RT-PCR results and clinical diagnosis. In
      summary, the RT-PCR panel provides an improved approach to obtain new insights
      into acute viral respiratory tract infections in children.

PMID- 8748291
TI  - Genotypic and phenotypic characterization of Escherichia coli isolates from dogs
      manifesting attaching and effacing lesions.
AB  - Thirteen Escherichia coli isolates from dogs manifesting attaching and effacing
      lesions were characterized genetically with respect to the presence of the
      following virulence determinants associated with human enteropathogenic E. coli
      (EPEC): eaeA, encoding the outer membrane protein intimin; eaeB, which is
      necessary for inducing signal transduction; bfpA, encoding the bundle-forming
      pilus; and the EAF (stands for EPEC adherence factor) plasmid. These isolates
      were also analyzed phenotypically with respect to adherence to mammalian cells in
      vivo and in vitro. Nine of these 13 isolates were found to be eaeA positive by
      PCR: four of these nine were eaeB positive. The 5' end, but not the 3' end, of
      the eaeA gene was amplified by PCR when primers derived from the eaeA gene of
      EPEC were used. Six and eight of these 13 isolates were found to be bfpA positive
      and EAF positive, respectively. The bfpA gene and EAF locus were found on high
      molecular-weight plasmids, whereas the eaeA and eaeB genes were chromosomally
      located when present. Only one canine E. coli isolate, 4221, which was positive
      for eaeA, eaeB, bfpA, and EAF, adhered to HEp-2 cells in a localized manner and
      was positive in the fluorescence actin staining test. The nine eaeA-positive
      isolates adhered to the mucosal surface of piglet ileal explants and induced some
      microvillus effacement. However, when tested in experimentally inoculated
      gnotobiotic piglets, isolate 4221 did not induce attaching and effacing lesions
      at any level of the intestinal tract. Our results indicate that canine E. coli
      isolates associated with attaching and effacing lesions share some properties
      with human EPEC but form a heterogeneous group.

PMID- 8748292
TI  - Variant colony surface antigenic phenotypes within mycoplasma strain populations:
      implications for species identification and strain standardization.
AB  - Immunobinding assays with mycoplasma colonies on agar plates (immunofluorescence
      and immunoperoxidase techniques) or with imprints of colonies transferred to
      solid supports (colony immunoblotting) are widely used as standard diagnostic
      tests for serological species identification of mycoplasma isolates. However, in
      light of the high rate of variability of surface antigens in many mycoplasmas,
      diagnostic data obtained with these techniques require a more critical
      evaluation. In this report, we demonstrate with some examples that mycoplasma
      surface variability based on alterations in expression, in size, and in surface
      presentation of integral and peripheral membrane proteins may lead to
      misinterpretation of colony immunostaining reactions obtained by using specific
      monoclonal antibodies as well as conventional diagnostic hyperimmune sera. To
      more easily identify phenotypically mixed isolates or samples which contain more
      than one species, we have introduced some minor modifications of the colony
      immunoblot technique which provide sharp signals of positive as well as negative
      reactions and enable identification of cryptic epitopes. It is further
      demonstrated that because of the variability in colony surface antigenic
      phenotype, mycoplasma strains, including well-established reference and other
      prototype strains which are used under the same designation in many laboratories,
      can differ markedly in their antigen profiles and their potentially virulence
      related surface properties, since they are usually purified by filter cloning and
      often propagated by subcultivation of randomly selected agar-grown
      subpopulations. We conclude from this study that because of this surface
      variability, the establishment of criteria for standardization of mycoplasma
      strains and diagnostic antisera is urgently required in order to obtain
      reproducible results in different laboratories.

PMID- 8748293
TI  - Genotype profile of human polyomavirus JC excreted in urine of immunocompetent
      individuals.
AB  - The human polyomavirus JC (JCV) causes the central demyelinating disease
      progressive multifocal leukoencephalopathy in about 5% of AIDS patients. To
      characterize the type profile of JCV in a control population in the United
      States, 54 females (10 to 79 years of age; average age, 43.4 years) and 51 males
      (18 to 94 years of age; average age, 47.9 years) were examined for the excretion
      of different genotypes of JCV in their urine by PCR followed by direct cycle
      sequencing. The group consisted of 89 patients of a general medical clinic in
      addition to 16 healthy volunteers. The overall incidence of JC viruria was 43 of
      105 (40.9%) subjects, with a marked increase for those subjects above the age of
      30 years. Two men were found to excrete two different types of JCV at the same
      time, indicating double infections. Of the three different genotypes of JCV
      identified to date, type 1 strains (European) were the most common in this cohort
      (64% of total strains) followed by type 2 (East Asian) (18%). No type 3 (East
      African) strains were detected. Indirect evidence for the existence of JCV type 3
      was found in seven individuals (16%) in the form of a type 1/3 recombinant (also
      called type 4). In addition, a single example of JCV which differs from types 1,
      2, and 3 and may represent a phylogenetically older type (type 5) was found in a
      59-year-old African-American. Delineation of sequence variations between JCV
      types is essential for the design of primers for sensitive PCR with clinical
      samples.

PMID- 8748294
TI  - Cloning of Brucella abortus gene and characterization of expressed 26-kilodalton
      periplasmic protein: potential use for diagnosis.
AB  - Brucella spp. are the causative agents of brucellosis in many different hosts,
      including humans. Most of the serological methods of diagnosis are based on the
      detection of antilipopolysaccharide antibodies, which makes the differentiation
      of vaccinated animals from infected animals difficult. By using molecular biology
      techniques, a gene that encodes a 26-kDa protein (BP26) was isolated from a
      Brucella abortus S19 genome lambda gt11 library. This protein is in the periplasm
      of B. abortus and in transformed Escherichia coli. It is exported to the
      periplasm via a preprotein of 29 kDa with a signal sequence of 28 amino acids.
      The nucleotide and amino acid sequences of this gene and protein did not show any
      similarity with those of previously sequenced genes. The use of this protein in
      Western blotting allowed the differentiation between vaccinated bovines from
      infected bovines and the detection of infected rams: on the other hand, sera from
      human patients with active brucellosis were positive, while sera from human
      patients with chronic brucellosis or without clinical signs were nonreactive.
      BP26 might be of value as an antigen for serological diagnosis of brucellosis in
      different mammals.

PMID- 8748295
TI  - Comparison of spiral gradient endpoint and agar dilution methods for
      susceptibility testing of anaerobic bacteria: a multilaboratory collaborative
      evaluation.
AB  - A multilaboratory collaborative study was carried out to assess the utility of
      the spiral gradient endpoint (SGE) method for the determination of the
      antimicrobial susceptibilities of anaerobes and to evaluate the equivalence of
      the MICs obtained by the SGE method with those obtained by the reference agar
      dilution method of the National Committee for Clinical Laboratory Standards. The
      standard deviation of the MIC obtained by the SGE method for the five
      participating laboratories was +/- 0.26 of a twofold dilution, whereas it was +/-
      1 twofold dilution by the reference method. The interlaboratory reproducibility
      of the results for two control strains tested with imipenem, chloramphenicol, and
      metronidazole indicated that 96% of the measurements fell within +/- 1 twofold
      dilution of the mode. The equivalence of the SGE method with the agar dilution
      method was assessed with a wide variety of anaerobic organisms. The MICs by both
      methods were within 1 doubling dilution in 93% of the measurements (n = 1,074).
      Discrepancies generally occurred with those organism-drug combinations that
      resulted in tailing endpoints (Fusobacterium nucleatum, 86% agreement) or in
      cases of light growth (Peptostreptococcus spp., 86% agreement).

PMID- 8748296
TI  - Field inversion gel electrophoretic analysis of Legionella pneumophila strains
      associated with nosocomial legionellosis in children.
AB  - Two nosocomial cases of Legionnaires' disease occurred in children. Legionella
      pneumophila serogroup 1 was isolated from both patients and 30 of 39 plumbing
      system sites in the hospital. The patient and hospital environmental isolates
      yielded identical field inversion gel electrophoretic patterns which differed
      from patterns observed with epidemiologically unrelated strains.

PMID- 8748297
TI  - Use of gen-probe probe competition assay as a supplement to probes for direct
      detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urogenital
      specimens.
AB  - The potential for development of a cost-effective protocol for selective use of
      the Gen-Probe probe competition assay (PCA) in conjunction with PACE 2 for direct
      detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urogenital
      specimens that would not compromise patient care was investigated. To accomplish
      this, PCA data from testing performed over 12 months were retrospectively
      reviewed. Of 237 samples that were presumptively positive for C. trachomatis by
      initial probe assay and could be tested by PCA, positive PCA results were
      obtained for 100, 79, and 59%, respectively, of specimens that gave a signal of
      more than 1,500, 1,000 to 1,500, and less than 1,000 relative light units (RLU).
      For the 141 specimens that were presumptively positive for N. gonorrhoeae and
      could be tested by PCA, positive PCA results were obtained for 99, 80, and 42%,
      respectively, of samples with a signal of more than 1,500, 1,000 to 1,500, and
      less than 1,000 RLU. These data indicate that PCA should be a routine supplement
      to Gen-Probe PACE 2 for specimens with an initial signal by probe assay of less
      than 1,500 RLU and may not be necessary for samples yielding a signal of more
      than 1,500 RLU.

PMID- 8748298
TI  - Evaluation of new computer-enhanced identification program for microorganisms:
      adaptation of BioBASE for identification of members of the family
      Enterobacteriaceae.
AB  - We report the use of BioBASE, a computer-enhanced numerical identification
      software package, as a valuable aid for the rapid identification of unknown
      enteric bacilli when using conventional biochemicals. We compared BioBASE
      identification results with those of the Centers for Disease Control and
      Prevention's mainframe computer to determine the former's accuracy in identifying
      both common and rare unknown isolates of the family Enterobacteriaceae by using
      the same compiled data matrix. Of 293 enteric strains tested by BioBASE, 278
      (94.9%) were correctly identified to the species level; 13 (4.4%) were assigned
      unacceptable or low discrimination profiles, but 8 of these (2.7%) were listed as
      the first choice; and 2 (0.7%) were not identified correctly because of their
      highly unusual biochemical profiles. The software is user friendly, rapid, and
      accurate and would be of value to any laboratory that uses conventional
      biochemicals.

PMID- 8748299
TI  - Comparison of two leukocyte extraction methods for cytomegalovirus antigenemia
      assay.
AB  - We carried out a prospective, parallel, and blind study on 113 blood samples from
      immunocompromised patients in order to compare two leukocyte extraction methods
      (6% dextran sedimentation and Polymorphprep separation) for cytomegalovirus (CMV)
      antigenemia assay. CMV was detected in 38 samples by antigenemia assay (34 by
      dextran sedimentation and 35 by Polymorphprep separation). No differences either
      in the number of positive specimens (P = 1) or in the mean CMV-positive cell
      counts (P = 0.41) were observed between the two leukocyte extraction methods. In
      conclusion, the two methods performed equally well for this assay.

PMID- 8748300
TI  - Natamycin as a selective antifungal agent in media for growth of Legionella spp.
AB  - The growth of 18 different Legionella sp. strains and 76 different yeast isolates
      was tested on buffered charcoal yeast extract medium supplemented with alpha
      ketoglutarate (BCYE alpha medium) and with natamycin, an antifungal agent.
      Bacterial growth was no different on BCYE alpha medium made with or without
      natamycin, whereas complete inhibition of yeasts occurred in BCYE alpha medium
      containing 200 to 500 micrograms of natamycin per ml. Selective BCYE alpha media
      made with natamycin rather than anisomycin had no (formulation with vancomycin,
      polymyxin B, and agar) or little (formulation with cefamandole, polymyxin B, and
      agar) inhibitory effect on the growth of 14 different Legionella sp. bacteria.
      Natamycin is an inexpensive alternative to anisomycin in the formulation of
      selective BCYE alpha media.

PMID- 8748301
TI  - Demonstration of borna disease virus RNA in peripheral blood mononuclear cells
      derived from domestic cats in Japan.
AB  - Borna disease virus (BDV) naturally infects horses, sheep, and several other
      species, including humans, and it is believed to be related to neurological
      disorders. BDV infection in domestic cats has also been demonstrated by
      serological assays. We demonstrated for the first time BDV RNA in peripheral
      blood mononuclear cells from 11 of 83 (13.3%) randomly selected domestic cats in
      Japan by nested reverse transcriptase-PCR. The BDVs from cats were similar to but
      slightly different from those from horses and humans, as shown by sequencing the
      reverse transcriptase-PCR products. None of the cats was positive for both BDV
      RNA and anti-BDV antibodies.

PMID- 8748302
TI  - Genomic DNA fingerprint analysis of biotype 1 Gardnerella vaginalis from patients
      with and without bacterial vaginosis.
AB  - Of the 20 biotype 1 Gardnerella vaginalis isolates analyzed, 10 from patients
      with bacterial vaginosis and 10 from patients without bacterial vaginosis, none
      shared the same DNA fingerprint. However, a 1.18-kb HindIII fragment was common
      among 18 of the 20 biotype 1 isolates in a restriction fragment length
      polymorphism analysis with a 7.9-kb G. vaginalis DNA probe.

PMID- 8748303
TI  - Genetic heterogeneity of M type 3 group A streptococci causing severe infections
      in Tayside, Scotland.
AB  - To explain the worldwide increase in the frequency of severe infections by group
      A streptococci, molecular techniques are increasingly being employed to evaluate
      the genetic relationships of strains. We used restriction endonuclease analysis,
      pulsed-field gel electrophoresis (PFGE), the PCR, ribotyping, and DNA sequence
      analysis in a study of 13 group A streptococci isolated from a cluster of cases
      of serious infections over a 3-month period in Tayside, Scotland. Eight of the
      strains were M type 3; molecular characterization identified two subclones. The
      first, displaying PFGE profile 4, has been observed in Northern Scotland and has
      been circulating in New Zealand for over a decade. The second subclone has been
      documented only in the United Kingdom; it was first seen in 1993 in Scotland.
      Sequence analysis of emm-3 genes further differentiated the PFGE 4 subclone. DNA
      sequence analysis of virulence factors supports the suggestion that they may have
      recently been acquired by horizontal gene transfer.

PMID- 8748304
TI  - Rapid and sensitive detection of enteroviruses in specimens from patients with
      aseptic meningitis.
AB  - A 5-h PCR assay (Amplicor enterovirus test) was compared with viral culture for
      the detection of enteroviruses in cerebrospinal fluid. Of the cerebrospinal fluid
      specimens collected during a summer outbreak of aseptic meningitis, 34% were
      positive by viral culture whereas 66% were positive by the Amplicor PCR,
      suggesting that this technique improves the diagnosis of enteroviral meningitis.

PMID- 8748305
TI  - Comparison of ribotyping and genome fingerprinting of Pseudomonas aeruginosa
      isolates from cystic fibrosis patients.
AB  - Forty Pseudomonas aeruginosa strains, previously characterized by pulsed-field
      gel electrophoresis, were ribotyped with EcoRI, BamHI, ClaI, and PvuII.
      Ribotyping with PvuII proved to be as discriminatory as pulsed-field gel
      electrophoresis with XbaI or DraI while EcoRI and BamHI were not. ClaI
      contributed further ribotypes, some of which might be due to a transposable
      element.

PMID- 8748306
TI  - Diagnosis of parvovirus B19 infection by detection of specific immunoglobulin M
      antibody in saliva.
AB  - Serum and saliva samples were simultaneously collected from patients with B19
      infection. Specimens were collected in a period of 1 to 18 days after the onset
      of symptoms. Saliva samples were collected with a commercial device, OraSure. The
      quality of these samples was evaluated by determining the concentration of total
      immunoglobulin G (IgG) by an enzyme immunoassay. The concentration of IgG in
      these samples ranged from 4.8 to > 250 mg/liter. B19 infection was confirmed for
      20 patients by testing sera in a 1: 100 dilution by an IgM capture enzyme
      immunoassay (MACEIA) and an IgM capture hemadherence test (MACHAT). Saliva
      samples from these IgM-positive patients were tested neat by MACEIA and MACHAT.
      IgM could be detected in 11 of 20 (55%) samples by MACEIA and in 15 of 18 (83%)
      samples by MACHAT. Serum and saliva samples from a further 17 patients with rash
      were also tested. All of these specimens were unreactive by both assays. These
      results show that saliva may be a convenient alternative to serum for the
      diagnosis of recent B19 infection.

PMID- 8748307
TI  - Recovery of Histoplasma capsulatum from BACTEC TB media.
AB  - From 1990 through 1994, we fortuitously isolated Histoplasma capsulatum from six
      patients with AIDS whose specimens of blood were processed by the BACTEC system
      using Middlebrook broth selective for acid-fast bacilli (13A medium). Growth
      indices became positive after an average of 17 days of incubation (range, 11 to
      20 days). No acid-fast bacilli were seen, but small budding yeasts characteristic
      of H. capsulatum were present.

PMID- 8748308
TI  - Comparison of rectal and perirectal swabs for detection of colonization with
      vancomycin-resistant enterococci.
AB  - Patients whose gastrointestinal tracts are colonized with vancomycin-resistant
      enterococci (VRE) may serve as a reservoir for nosocomial transmission. We
      compared the sensitivities and concordance of several methods used to detect VRE
      colonization. Eighty-two paired rectal and perirectal swabs were obtained from 13
      patients over a 9-day period. The sensitivity of both rectal and perirectal swabs
      was 79%. There was 100% concordance of culture results between simultaneously
      obtained rectal and perirectal swabs, and the quantities of growth were similar
      by these two methods of detection. Our data suggest that rectal and perirectal
      swabs are equally sensitive for the detection of VRE colonization.

PMID- 8748309
TI  - Comparison of four enzyme immunoassays for detection of human T-cell lymphotropic
      virus type 2 antibodies.
AB  - Four licensed enzyme immunoassay (EIA) kits for the measurement of antibody to
      human T-cell lymphotropic virus (HTLV) type 1, one from Organon Teknika Corp.
      (OTC), one from Cambridge Biotech Corp. (CBC), and two from Abbott Laboratories
      (the 1993 modification [Abb 93] and the 2.0 version licensed in 1995 [Abb 95]),
      were evaluated for sensitivity and specificity in the detection of HTLV type 2
      antibody, and the results were compared with those previously obtained with
      earlier kit versions. The CBC, Abb 95, Abb 93, and OTC kits had sensitivities of
      99.7, 97.6, 96.8, and 96.2%, respectively, compared with sensitivities of 89.1
      and 60% for the Abbott and CBC (previously DuPont) kits, respectively, licensed
      in 1988. Thus, the abilities of commercial kits to detect HTLV antibody have
      improved. The relative specificities of the CBC, Abb 95, Abb 93, and OTC kits
      with negative blood donor specimens that had been reactive with the 1988 CBC EIA
      kit were 92.9, 64.5, 78.8, and 62.6%, respectively. Compared with those of the
      1988 versions, the specificity of the Abbott EIA has decreased and the
      specificity of the CBC kit has been significantly improved.

PMID- 8748310
TI  - Serratia rubidaea as an invasive pathogen.
AB  - Serratia rubidaea biotype 1 was isolated from the bile and blood of a patient
      with a bile tract carcinoma obstructing the common bile duct and who underwent
      invasive procedures. The infection was cleared after adequate treatment with
      antibiotics.

PMID- 8748311
TI  - D-mannitol in cerebrospinal fluid of patients with AIDS and cryptococcal
      meningitis.
AB  - Cryptococcal meningitis (CM) is associated with raised intracranial pressure
      which is linked with serious neurological sequelae. Cryptococcus neoformans
      produces D-mannitol in vitro and in experimental meningitis in rabbits. Mannitol
      present in the cerebrospinal fluid (CSF) of CM patients could exacerbate raised
      intracranial pressure and contribute to neurological damage. To link CSF mannitol
      to cryptococcal infection, levels of mannitol in the CSF of AIDS patients with CM
      were measured by gas-liquid chromatography. Mannitol was detected in 19 of 21
      samples (range, 1.5 to 26.2 mg/liter), but there was no quantitative correlation
      between the mannitol concentration and the cryptococcal antigen titer.

PMID- 8748312
TI  - Improved performance of Gen-Probe Amplified Mycobacterium Tuberculosis Direct
      Test when 500 instead of 50 microliters of decontaminated sediment is used.

PMID- 8748313
TI  - Identification of a 25-kilodalton protein of Mycobacterium bovis BCG to
      distinguish BCG strains from Mycobacterium tuberculosis.
AB  - Mycobacterium bovis BCG vaccine strains were compared with Mycobacterium
      tuberculosis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A 25
      kDa protein observed in the BCG strains was absent in M. tuberculosis. Rabbit
      antibodies specific to the 25-kDa protein uniquely identified this protein in BCG
      strains but not in M. tuberculosis. It is suggested that the 25-kDa protein and
      polyclonal antibodies directed against this antigen can be exploited to
      distinguish BCG strains from M. tuberculosis.

PMID- 8748314
TI  - Microbiological findings about pulmonary cryptosporidiosis in two AIDS patients.
AB  - There is no known treatment for pulmonary cryptosporidiosis, a rare complication
      of intestinal cryptosporidiosis in AIDS patients. We report two cases of
      cryptosporidiosis which were unusual because (i) extracellular invasive forms of
      the parasite were found in the bronchoalveolar lavage and (ii) the outcome was
      favorable in one patient after treatment with azithromycin.

PMID- 8748315
TI  - Filtration of BACTEC 7H12B broth cultures for identification of Mycobacterium
      tuberculosis complex by AccuProbe.

PMID- 8748316
TI  - Reliability of pasco MIC system for use in detection of resistant Streptococcus
      pneumoniae.

PMID- 8748317
TI  - Value of terminal subcultures for blood cultures monitored by BACTEC 9240.

PMID- 8748318
TI  - Pharmacokinetics of a novel HIV-1 protease inhibitor incorporated into
      biodegradable or enteric nanoparticles following intravenous and oral
      administration to mice.
AB  - CGP 57813 is a peptidomimetic inhibitor of human immunodeficiency virus type 1
      (HIV-1) protease. This lipophilic compound was successfully entrapped into
      poly(D,L-lactic acid) (PLA) and pH sensitive methacrylic acid copolymers
      nanoparticle. The intravenous administration to mice of PLA nanoparticles loaded
      with CGP 57813 resulted in a 2-fold increase of the area under the plasma
      concentration-time curve, compared to a control solution. An increase in the
      elimination half-life (from 13 to 61 min) and in the apparent volume of
      distribution (1.7-3.6 L/kg) was observed for the nanoparticle incorporated
      compound vs control solution. Following oral administration, only nanoparticles
      made of the methacrylic acid copolymer soluble at low pH provided sufficient
      plasma levels of CGP 57813. In vitro, these nanoparticles dissolved completely
      within 5 min at pH 5.8. PLA nanoparticles, which are insoluble in the
      gastrointestinal tract, did not provide significant plasma concentrations of CGP
      57813. From these observations, one can conclude that the passage of intact PLA
      nanoparticles across the gastrointestinal mucosa appears to be very low.

PMID- 8748319
TI  - Relationships between crystal structures, thermal properties, and solvate
      stability of dialkylhydroxypyridones and their formic acid solvates.
AB  - Four 1,2-dialkyl-3-hydroxy-4-pyridones (DAHPs), which are iron chelators
      potentially suitable for oral administration, and their formic acid solvates
      (DAHP-Fs) were examined in powder form by powder X-ray diffraction (PXD),
      differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), and
      hot-stage microscopy (HSM). The experimental PXD pattern of each DAHP-F is
      different from that of the corresponding DAHP, indicating different crystalline
      phases. The PXD patterns calculated from the published crystal structures closely
      resemble the corresponding PXD patterns determined experimentally, indicating
      that the powdered materials studied are structurally identical with the single
      crystals previously examined. The DAHPs have similar DSC profiles consisting of
      melting followed by vaporization. The DSC profiles of the DAHP-Fs share five
      common features: melting and desolvation of the solvate, crystallization of the
      nonsolvate, vaporization of the released formic acid, melting of the nonsolvate,
      and vaporization of the nonsolvate. The weight loss steps in TGA indicate that
      each DAHP-F contains 1 mol of formic acid/mol of DAHP. The threshold temperature
      for desolvation of each DAHP increases with decreasing length of the hydrogen
      bond between the pyridone carbonyl oxygen and the formic acid carboxyl proton,
      corresponding to an increase in solvate stability. Thus, the relative stabilities
      of the solvates are delineated and are related to the length of the hydrogen bond
      between the DAHP and the formic acid molecules.

PMID- 8748320
TI  - Antitumor efficacy of taxane liposomes on a human ovarian tumor xenograft in nude
      athymic mice.
AB  - Taxanes such as paclitaxel (Taxol) and docetaxel (Taxotere) are promising agents
      for use against ovarian cancer and other malignancies. Recently, SB-T-1011, a
      semisynthetic taxane, has been prepared from 14-hydroxy-10-deacetylbaccatin III.
      SB-T-1011 shows similar or greater in vitro cytostatic activity than paclitaxel,
      depending on the tumor cell line. The administration of taxanes is problematic
      due to their low solubility in most pharmaceutically acceptable solvents;
      formulations used clinically contain Cremophor/ethanol (diluent 12) or
      polysorbate 80/ethanol, excipients which may cause serious adverse effects. To
      eliminate these vehicles, we have prepared paclitaxel liposome formulations. The
      objective of the present work was to evaluate the antitumor activity of
      paclitaxel and two semisynthetic analogs in Cremophor-based and liposomal
      formulations. Antitumor activity was evaluated against A121a, a taxane-sensitive
      human ovarian tumor, growing as subcutaneous xenografts in athymic nude mice.
      Free and liposomal formulations of each taxane showed similar antitumor effect.
      The antitumor activity of paclitaxel and SB-T-1011 was similar, and docetaxel was
      more potent than either paclitaxel or SB-T-1011. Overall, taxane liposomes were
      better tolerated and more easily administered iv than taxane formulated in
      Cremophor/ethanol.

PMID- 8748321
TI  - The effect of mannitol on the oral bioavailability of cimetidine.
AB  - The aim of the study was to investigate whether mannitol at amounts relevant to
      pharmaceutical formulations would alter the oral bioavailability of cimetidine, a
      drug primarily absorbed from the small bowel. Seven healthy male subjects each
      received four formulations, a chewable tablet or a solution, containing 0.200 g
      of cimetidine and either 2.264 g of mannitol or sucrose, in a randomized four-way
      cross-over study. Frequent blood samples were taken over a 24 h period to allow a
      cimetidine plasma profile to be obtained for each formulation. Transit of the
      radiolabeled formulations was followed by gamma scintigraphy. Statistically
      significant reductions in the AUC0-24 and maximum plasma concentration values
      were observed with the mannitol dosage forms compared to the sucrose controls.
      The mean small intestinal transit times were shortened after administration of
      the mannitol solution and tablet; the transit time of the solution was
      significantly shorter with values 23% of those for the sucrose solution. The
      implication of the study findings is that excipients cannot always be regarded as
      "inert" substances that can be incorporated into a formulation without having any
      deleterious effect on the overall in vivo behaviour of the product.

PMID- 8748322
TI  - Comparative evaluation of the predictive power of calculation procedures for
      molecular lipophilicity.
AB  - The predictive power of four calculation procedures for molecular lipophilicity
      is checked by comparing with experimental data (log P and chromatographical RMw)
      taken from the literature. Two sets of test compounds are used: the first
      comprises simple organic molecules and the second consists of more complicated
      drug molecules. Our comparative evaluation leads us to conclude that the
      predictive power is significantly better for not too complicated organic
      molecules than for drugs with complicated structural pattern. The four
      investigated calculation procedures should be arranged in two groups with
      significantly differing predictive power: (a) Rekker and Hansch/Leo and (b)
      Ghose/Crippen and Suzuki/Kudo. This conclusion is based on a statistical control
      using log P and RMw as the independent parameters. Correlations have in common:
      (1) slopes in correlations with calculated data based on fragmental methods are
      not significantly different from 1; calculations with data from atom-based
      procedures show up in most cases with slopes below 1. (2) The accompanying
      overall statistics underline the superiority of the fragmental methods. We think
      that all four tested calculation procedures have their own restrictions; for
      future development we would advise a thorough reconsideration of structural
      effects not fully (or even not at all) incorporated in the data sets. Special
      attention will have to be paid to the conformational aspects of lipophilic
      behavior.

PMID- 8748323
TI  - Interaction of 6-p-toluidinylnaphthalene-2-sulfonate with beta-cyclodextrin.
AB  - The interaction of 6-p-toluidinylnaphthalene-2-sulfonate (TNS) with beta
      cyclodextrin was investigated in 0.1 M phosphate buffer at pH 7.4 by fluorescence
      spectroscopy. Using the fluorescence enhancement of TNS in the presence of beta
      cyclodextrin, the thermodynamic parameters for the formation of two kinds of the
      inclusion complex (molar ratio of beta-cyclodextrin to TNS = 1:1 and 2:1) were
      determined as follows: delta G degree 1 (1:1 complex) = -20.0 kJ mol-1 at 25
      degrees C, delta H degree 1 = -19.6 kJ mol-1, delta S degree 1 = -1.7 J mol-1 K
      1, delta G degree 2 (2:1 complex) at 25 degrees C = -6.14 kJ mol-1, delta H
      degree 2 = -2.80 kJ mol-1, delta S degree 2 = 16.7 J mol-1 K-1. From the
      thermodynamic parameters, the main driving force for the 1:1 inclusion complex
      formation was considered to be the van der Waals-London dispersion force, while
      the contribution of the hydrophobic interaction was small. Also, the hydrogen
      bonding was suggested to contribute to the inclusion complex formation. The main
      driving force for the 2:1 inclusion complex formation was the hydrophobic
      interaction. Also, from the measurements of proton nuclear magnetic resonance
      spectra and studies with Corey-Pauling-Koltun atomic models, the probable
      structure was determined and discussed in connection with the thermodynamic
      parameters.

PMID- 8748324
TI  - Transdermal delivery of drugs with differing lipophilicities using azone analogs
      as dermal penetration enhancers.
AB  - Six model drugs were selected for this study based on their degree of
      lipophilicity as represented by their log P values (range = -0.95 to 3.51). They
      included 2,4-dihydroxy-5-fluoropyrimidine (5-fluorouracil); 1,3,7
      trimethylxanthine (caffeine); [(2-hydroxybenzoyl)amino]-acetic acid (salicyluric
      acid); 2-hydroxybenzoic acid (salicylic acid); 9 alpha-fluoro-16 alpha
      hydroxyprednisolone 16 alpha, 17 alpha-acetonide (triamcinolone acetonide); and
      alpha-methyl-4-[2-methylpropyl]benzeneacetic acid (ibuprofen). Six dermal
      penetration enhancers [Azone or 1-dodecylhexahydro-2H-azepin-2-one (1), N-dodecyl
      2-pyrrolidinone (2), N-dodecyl-2-piperidinone (3), N-dodecyl-N-(2
      methoxyethyl)acetamide (4), N-(2,2-dihydroxyethyl)dodecylamine (5), and 2-(1
      nonyl)-1,3-dioxolane (6)] were tested in vitro across full-thickness hairless
      mouse skin with each of the drugs. The relationship between lipophilicity (log P)
      and efficacy (represented by the enhancement ratio of flux) of the drugs when
      coadministered with the enhancers was examined using linear regression. The three
      cyclic enhancers (1-3) exhibited linear relationships, indicating that they were
      more effective at enhancing the penetration of hydrophilic drugs R2 = 0.8997 for
      1, 0.8801 for 2, and 0.804 for 3) when evaluating all the model drugs except
      triamcinolone acetonide (TA). The two acyclic enhancers (4 and 5) showed a
      similar relationship, but their correlation coefficients were lower at 0.6463 for
      4 and 0.6213 for 5. Studies with the dioxolane (6) yielded no relationship
      between the lipophilicity of the drug and the efficacy of the enhancer, with an
      R2 of 0.002. Overall, 6 was the least effective enhancer studied. The steroid TA
      was not included in the linear regression analysis. Of the six model drugs
      studied, TA exhibited the largest increase in transdermal delivery when enhancers
      1-6 were used.

PMID- 8748325
TI  - Effect of cogrinding with various kinds of surfactants on the dissolution
      behavior of phenytoin.
AB  - The physicochemical properties of phenytoin (PHT) combined with various kinds of
      surfactants at 40 w/w % such as sodium lauryl sulfate (SLS), sodium deoxycholate
      (DCNa), and the sucrose ester of stearic acid (SE) by a cogrinding method were
      investigated by X-ray diffraction analysis, Fourier transformed infrared (FT-IR)
      spectroscopy, differential scanning calorimetry (DSC), and dissolution kinetics
      in 2nd fluid (Japanese Pharmacopoeia XII, pH 6.8, 37 degrees C). All X-ray
      diffraction peak intensities of the coground mixtures were decreased by grinding,
      and the product with DCNa grinding for 3 h transformed into a noncrystalline
      solid, but the products with SE and SLS were not. The solubilities of ground
      products with SLS and SE were almost the same as those of respective physical
      mixtures. However, the apparent solubility of ground products with DCNa was 28.7
      times higher than that of the physical mixture.

PMID- 8748326
TI  - Characterization of polymorphic forms of fluconazole using Fourier transform
      Raman spectroscopy.
AB  - Detailed Fourier transform Raman spectra of fluconazole have been recorded and
      the main spectral features of fluconazole have been assigned to its vibrational
      modes. Two different polymorphic forms of fluoconazole were identified in two
      spectral regions, 150-1700 cm-1 and 2700-3200 cm-1, respectively. The FT-Raman
      results agree well with those of differential scanning calorimetry and X-ray
      powder diffractometry. The combination of definiteness with easy sample handling
      makes FT-Raman spectroscopy a valuable technique for the analysis of polymorphs.

PMID- 8748327
TI  - Effect of YM294, recombinant human interleukin-11, on carboplatin-induced
      thrombocytopenia in rats.
AB  - We investigated the effects of YM294, recombinant human interleukin-11, on
      changes in blood cell levels in carboplatin-treated rats. Continuous infusion of
      YM294 was carried out by either intravenous or subcutaneous injection (10 and 100
      micrograms/rat/day) for 14 days via an implanted osmotic pump. Carboplatin (30
      mg/kg iv) significantly decreased platelet counts on days 7-9; counts
      subsequently increased to levels greater than the initial level by day 21.
      Intravenous administration of YM294 inhibited this decrease in platelet count by
      carboplatin and increased the platelet count in the recovery phase in a dose
      dependent manner. YM294 also showed effects on carboplatin-induced changes in
      white blood cell and red blood cell counts; these effects seemed, however, to be
      neither consistent nor dose-dependent. The effects of YM294 on subcutaneous
      infusion were similar to those on intravenous infusion. The effect of YM294 on
      the survival of rats treated with a higher dose of carboplatin (60 mg/kg iv) was
      also investigated. YM294 (100 micrograms/rat/day) given by continuous intravenous
      infusion increased the 30-day survival rate. These results confirm the utility of
      YM294 in the treatment of thrombocytopenia after chemotherapy.

PMID- 8748328
TI  - Mathematical model and dimensional analysis of glycocholate binding to
      cholestyramine resin: implications for in vivo resin performance.
AB  - In large doses, cholestyramine resin lowers blood serum cholesterol by binding
      bile salts in the intestinal lumen and thus increases the fecal excretion of bile
      salts. In order to gain a better understanding of the low in vivo potency of
      cholestyramine, mathematical models estimating the amount of glycocholate bound
      per gram of cholestyramine and the free glycocholate concentration were derived
      and employ the capacity-corrected molar selectivity coefficient. Predictions of
      the quantity of glycocholate bound per gram of cholestyramine and of the free
      glycocholate concentration matched observed values (r2 = 0.993 and r2 = 0.998,
      respectively) over a wide range of conditions. Simulated binding studies
      indicated the relative importance of several biopharmaceutical parameters for
      improved resin in vivo performance. Increasing resin selectivity of glycocholate
      over chloride has greatest therapeutic impact if bile salt sequestering is most
      important in the upper portion of the intestines. Furthermore, ion exchange
      phenomena was subjected to dimensional analysis and revealed the controlling
      factors as components of two dimensionless numbers, GC* and Cl*. Placing
      physiologic limits on values of GC* and Cl* suggests requisite selectivity
      properties of more potent bile acid sequestrants and dosing strategies to
      optimize current resin therapy.

PMID- 8748329
TI  - Drug release from hydrophilic matrices. 1. New scaling laws for predicting
      polymer and drug release based on the polymer disentanglement concentration and
      the diffusion layer.
AB  - Two scaling laws for predicting polymer and drug release profiles from
      hydrophilic matrices were developed. They were developed on the basis of the
      diffusion layer and the polymer disentanglement concentration, rho p,dis, the
      critical polymer concentration below which polymer chains detach off a gelled
      matrix that is undergoing simultaneous swelling and dissolution. The relation
      between rho p,dis and molecular weight, M1 for (hydroxypropyl)methylcellulose
      (HPMC) in water was established as rho p,dis (g/mL) varies M-0.8. This power-law
      relationship for rho p,dis, along with the diffusion layer adjacent to the gelled
      matrix, leads to the scaling law of mp(t)/mp(infinity) varies Meq-1.15, where
      mp(t)/mp(infinity) is the fractional HPMC release. The scaling law explains the
      observation that polymer and drug release rates decreased sharply with M at low M
      and approach limiting values at high M. Experimentally, mp(t)/mp(infinity) was
      found to scale with Meq as mp(t)/mp(infinity) varies Meq-0.93, where Meq is the
      equivalent matrix molecular weight. Moreover, fractional drug release,
      md(t)/md(infinity), followed Meq as md(t)/md(infinity) varies Meq-0.48. These two
      scaling laws imply that, if the release profiles are known for one composition,
      release profiles for other compositions can be predicted. The above two power
      laws lead to two master curves for mp(t)/mp(infinity) and md(t)/md(infinity),
      suggesting that the release mechanism for soluble drugs from HPMC matrices is
      independent of matrix compositions, presumably via a diffusion-controlled
      process. Limitations of the power laws are discussed.

PMID- 8748330
TI  - Drug release from hydrophilic matrices. 2. A mathematical model based on the
      polymer disentanglement concentration and the diffusion layer.
AB  - A comprehensive model is developed to describe the swelling/dissolution behaviors
      and drug release from hydrophilic matrices. The major thrust of this model is to
      employ an important physical property of the polymer, the polymer disentanglement
      concentration, rho p,dis, the polymer concentration below which polymer chains
      detach off the gelled matrix. For (hydroxypropyl)methylcellulose (HPMC) in water,
      we estimate that rho p,dis scales with HPMC molecular weight, M, as rho p,dis
      varies M-0.8. Further, matrix dissolution is considered similar to the
      dissolution of an object immersed in a fluid. As a result, a diffusion layer
      separating the matrix from the bulk solution is incorporated into the transport
      regime. An anisotropic expansion model is also introduced to account for the
      anisotropic expansion of the matrix where surface area in the radial direction
      dominates over the axial surface area. The model predicts that the overall tablet
      size and the characteristic swelling time correlate with rho p,dis qualitatively.
      Two scaling laws are established for fractional polymer (mp(t)/mp(infinity)) and
      drug (md(t)/md(infinity)) released as mp(t)/mp(infinity) varies M-1.05 and
      md(t)/md(infinity) varies M-0.24, consistent with the limiting polymer molecular
      weight effect on drug release. Model predictions for polymer and drug release
      agree well with observations, within 15% error. Evolution of water concentration
      profiles and the detailed structure of a swollen matrix are discussed.

PMID- 8748331
TI  - Simultaneous diffusion and metabolism of betamethasone 17-valerate in the living
      skin equivalent.
AB  - Simultaneous diffusion and metabolism of betamethasone 17-valerate was studied
      using betamethasone 17-valerate, betamethasone 21-valerate, and betamethasone as
      permeants. These corticosteroids were suspended in silicone adhesive and applied
      to an artificial living skin equivalent (LSE) for 72 h. When betamethasone was
      applied, no metabolites were detected in the receptor medium. Conversely, with
      betamethasone 21-valerate application, only betamethasone but no betamethasone 21
      valerate was detected in the receptor medium indicating the metabolism of the
      latter by skin esterases. When tested with the theory for simultaneous diffusion
      and metabolism, the result is consistent with the enzyme rate constant in the LSE
      homogenate measured in a previous study. When betamethasone 17-valerate was
      applied to the LSE, more than half of the total amount of corticosteroids
      detected in the receptor medium was unchanged, consistent with the previously
      reported chemical (as opposed to enzymatic) degradation half-life of about 8 h.
      This result also indicated that very little metabolism of betamethasone 17
      valerate occurred in the skin.

PMID- 8748332
TI  - Tenoxicam pharmacokinetics in rats: a population model.
AB  - This study was designed to establish the in vivo relationship between tenoxicam
      disposition and changes in plasma protein binding measured as an unbound fraction
      in plasma (fu). Tenoxicam was administered as a bolus 5-mg/kg dose, and total
      plasma concentrations, plasma albumin percentage, and fu were examined in five
      groups of rats (uremia or anephric states were experimentally induced in four
      groups to decrease plasma protein levels). Albumin levels were significantly
      decreased in all experimentally altered groups with respect to control animals (p
      < 0.01). A two-compartment population pharmacokinetic model that includes the
      effect of fu on the kinetic parameters was proposed to describe tenoxicam plasma
      concentration profiles. Plasma clearance (CL) increased but not proportionally
      with fu. Apparent volume of distribution of the central compartment (V) was
      linearly related to changes in fu and intercompartmental clearance was not
      affected by altered plasma protein binding. Expressing pharmacokinetic parameters
      as a function of fu resulted in a three- and five-fold decrease in the
      variability associated with CL and V, respectively.

PMID- 8748333
TI  - Pharmacokinetics of CTLA4Ig (BMS-188667), a novel immunosuppressive agent,
      following intravenous and subcutaneous administration to mice.

PMID- 8748334
TI  - Particle contamination in contrast media induced by disposable syringes.

PMID- 8748335
TI  - A meta-analysis of breast implants and connective tissue disease.
AB  - Case reports have raised questions about an increased risk of connective tissue
      diseases (CTDs) among women with breast implants. From the reviews of more than
      2,600 manuscripts, abstracts, and dissertations, this meta-analysis included 13
      epidemiology studies that provided a relative risk (RR) estimate for the possible
      association between breast implants and CTDs. The meta-analysis summary RR was
      0.76 for CTD in general (95% confidence interval [CI]: 0.55, 1.04; homogeneity p
      value = 0.073) and was 0.98 for scleroderma (95% CI: 0.57, 1.64; homogeneity p =
      0.006). Irrespective of which studies were aggregated in this meta-analysis,
      there was no significant increased risk for scleroderma, rheumatoid arthritis, or
      CTD in general. Conclusions from this study are consistent with the most recent
      review by the British Medical Devices Agency that found no scientific evidence to
      date of an increased risk of CTD associated with silicone gel breast implants.

PMID- 8748336
TI  - Endoscope-assisted rib cartilage harvesting.
AB  - The seventh and eighth costal cartilages were harvested through a small 1.5 to 2
      cm skin incision made in the midinframammary fold in female patients and the
      inferior border of the seventh coastal cartilage in male patients using an
      endoscope (total, 5 patients). The lateral half of the costal cartilage is
      dissected subperichondrially under direct visualization through the access
      incision, and the residual half is dissected subperichondrially using an
      endoscope. The advantages of using an endoscope to harvest costal cartilage
      include a better remote access incision site and a reduced risk of perforations
      of the pleura and bleeding through endoscopically-magnified visualization. This
      technique is particularly useful when the patient is a woman.

PMID- 8748337
TI  - Efficacy of the topical anesthetic cream, EMLA, in alleviating both needle
      insertion and injection pain.
AB  - To assess the efficacy of the topical anesthetic cream, EMLA, in alleviating the
      pain produced by infiltration of local anesthetic prior to surgical skin
      biopsies, a randomized, double-blind, placebo-controlled study was performed on
      54 patients undergoing 162 excisional biopsies. Both pain induced by needle
      insertion and pain induced by local injection were significantly diminished after
      topical application of EMLA cream. However, part of the effect was placebo,
      because the placebo ointment (Vaseline) also produced significant pain
      alleviation.

PMID- 8748338
TI  - Monitoring the axilla in patients with silicone gel implants.
AB  - Migration of silicone beyond the breast implant capsule may occur as a result of
      silicone bleed, leak, or rupture, and it may indicate failure of implant envelope
      integrity. We report a series of 23 patients with silicone implants who had
      axillary lymph node biopsies for palpable masses. Group 1 (n = 15) had biopsies
      performed an average of 6 years following aesthetic augmentation, and Group 2 (n
      = 8) had biopsies performed an average of 5 years after mastectomy
      reconstruction. All biopsies demonstrated foreign body reaction consistent with
      silicone migration. Five patients in Group 1 and two in Group 2 also had breast
      cancer detected by the axillary biopsy. Evaluation of the axilla utilized a
      combination of one or more techniques, including mammography, ultrasonography,
      magnetic resonance imaging, and fine-needle aspiration. We conclude that (1)
      routine evaluation of the axilla is mandatory in all patients with silicone
      breast implants; (2) an algorithmic approach in diagnosing axillary masses may be
      helpful, especially in augmentation patients; and (3) axillary masses detected by
      clinical examination or other means must be biopsied, even in the face of
      negative screening studies, because breast cancer may be coincidental with a
      silicone granuloma.

PMID- 8748339
TI  - Long-term sequelae following median sternotomy wound infection and flap
      reconstruction.
AB  - Use of muscle and omental flaps has been shown to provide reliable reconstruction
      of infected median sternotomy wounds; however, few reports emphasize the long
      term sequelae of the complication and its treatment. This study was performed to
      evaluate the long-term problems, including patient satisfaction and survival
      rate, in 88 patients with median sternotomy infections treated with muscle or
      omental flaps. Forty-two patients were available for long-term follow-up by
      telephone interview, with an average length of follow-up of 42 months. Forty
      three percent complained of chronic chest wall pain or discomfort, and 45%
      complained of sternal instability. After pectoralis major muscle flap
      reconstruction in 32 patients, 25% complained of upper extremity weakness, and
      56% complained of chest contour deformity. Delayed septic costochondritis or
      osteomyelitis occurred in 8%. Despite these unfavorable consequences, 72% and 83%
      of patients were satisfied with the cosmesis of the operation and the overall
      result, respectively. Furthermore, after hospital discharge, these patients seem
      to enjoy satisfactory longevity. By emphasizing the potential sequelae, further
      research interest may be stimulated in delineating their causes and in refining
      techniques of reconstruction.

PMID- 8748340
TI  - Meralgia paresthetica: etiology, diagnosis, and outcome of surgical
      decompression.
AB  - Entrapment of the lateral femoral cutaneous (LFC) nerve as a source of
      anterolateral thigh dysesthesias has been recognized for 100 years. Despite this
      historic recognition, its diagnosis today is often delayed, and definitive
      treatment of refractory cases by surgical decompression rarely reported. This
      study describes 26 LFC entrapments in 23 patients whose etiologies include iliac
      crest bone graft harvesting, seat belt injury associated with motor vehicle
      accident, and diabetes. Twenty-two of the 23 patients (25 of the 26 entrapments)
      achieved good to excellent outcomes following surgical decompression of the LFC
      nerve.

PMID- 8748341
TI  - The composite groin fascial free flap.
AB  - Seven patients with extensive loss of soft tissue, extensor tendon, and exposure
      of bone and joint of dorsum of hand and foot were treated with free composite
      flaps from the groin area. To retard the adhesion by scarring, membrane
      interposition between tendon and bone was recommended. The groin flap, based on
      superficial circumflex iliac vessels, was combined with a well-vascularized
      external oblique aponeurosis. The groin skin flap provided skin coverage, and the
      aponeurosis was used simultaneously to create a gliding surface for reconstructed
      tendons in a single one-stage procedure. All composite free-tissue transfers were
      successful. The advantages of this technique are: (1) a single, one-stage
      procedure; (2) fewer adhesions of reconstructed tendons, and no need of secondary
      tenolysis; and (3) good cosmesis and minimal morbidity at donor site.

PMID- 8748342
TI  - Microsurgical reconstruction of the lower extremity using the 3M microvascular
      coupling device in venous anastomoses.
AB  - Microsurgical reconstruction of the lower extremity presents a difficult problem
      to plastic surgeons; the rate of failure is higher than any other anatomical
      site. We reviewed our recent experience with lower extremity microsurgical
      reconstruction using the 3M vascular coupling device. We believe the excellent
      patency rate of the coupler may minimize the well-described problem of venous
      thrombosis in this challenging group of patients. This study involves a
      consecutive series of 11 patients who presented for reconstructive microsurgery
      of the lower extremity at NYU Medical Center hospitals between June 1 and
      September 1, 1994. Ten of 11 patients had free flap transfer to traumatic lower
      extremity injuries, whereas the remaining reconstruction was in a diabetic
      individual with a chronic wound. Fifteen microvascular venous anastomoses were
      performed; all but 1 was performed using the 3M coupler. Our experience with 11
      patients, involving 14 mechanically coupled venous anastomoses, demonstrated
      successful use of the coupler. No intraoperative or postoperative vascular
      complications occurred. The overall success rate of the 3M coupler for venous
      anastomoses was 100%, and all microvascular free flaps were successful. We
      recommend using the 3M coupling device for venous anastomoses during
      reconstructive microsurgery of the lower extremity. Our series demonstrates the
      safety and effectiveness of the 3M coupler in this challenging group of patients.
      In addition, a secondary benefit of the 3M coupler is a significant reduction in
      operative time.

PMID- 8748343
TI  - Modified orticochea pharyngoplasty for treatment of unilateral velopharyngeal
      incompetence.
AB  - Unilateral nasopharyngeal paralysis is a relatively rare cause of velopharyngeal
      incompetence. Few therapeutic modalities for this problem have been described. A
      modification of the orticochea sphincter pharyngoplasty was developed using only
      a unilateral flap for treatment of the symptoms of hypernasality and nasal
      reflux. This preliminary report summarizes the operative approach and the
      successful outcomes in 2 patients.

PMID- 8748344
TI  - Additional benefit of heparin in the thrombolytic salvage of ischemic skin flaps.
AB  - Microvascular thrombosis is known to play an important part in the cessation of
      flow seen in a flap following ischemia and revascularization. Its reversal, using
      thrombolytic therapy, is associated with higher rates of successful flap salvage.
      Although this procedure restores patency to the microcirculation, the damaged
      endothelial cell layer remains highly thrombogenic and a definite risk of
      rethrombosis exists in the early period of reperfusion. In an inferior epigastric
      flap model in a rat, we investigated the effect of additional heparin
      (subcutaneous and intravenous administration) following a standardized urokinase
      washout (100,000 iu) of the ischemic flaps. Flap survival was assessed at 1 week
      and morphological changes in the microcirculation were observed using electron
      microscopy. Results showed a significant increase in flap survival in the group
      receiving intravenous heparin following urokinase washout and suggest that
      systemic heparin may play a beneficial role in the early reperfusion period
      following thrombolytic flap salvage.

PMID- 8748345
TI  - The effects of lipo-prostaglandin E1 on axial pattern flaps in rabbits.
AB  - The effects of lipo-prostaglandin E1 (lipo-PGE1), lipid microspheres containing
      PGE1, on axial pattern flaps were examined using 12 x 20 cm axial pattern flaps
      based on the right superficial inferior epigastric vessels on the abdomens of
      rabbits. The surviving area of the skin flap in the lipo-PGE1 group (0.197 +/-
      14.1 cm2; n = 10) was significantly increased (p < 0.02) compared with the saline
      control group (110.4 +/- 5.5 cm2; n = 10). Changes in pedicle blood flow after
      lipo-PGE1 administration were determined using an ultrasonic pulsed Doppler
      flowmeter (n = 5). Blood flow in the artery was increased immediately after
      administration, and it was maintained for 40 minutes. The surface blood flow at
      the caudal end of the flap on the nonpedicle side, where it was poor, was
      measured using laserflowgraphy. Blood flow in the skin flap surface was improved
      5 to 15 minutes after lipo-PGE1 administration, and it was maintained for as long
      as 60 minutes. Venous occlusion of the skin flap was also improved (n = 3). In
      conclusion, lipo-PGE1 increased the blood flow in the axial pattern flaps,
      resulting in significant enlargement of the surviving skin flap area.

PMID- 8748346
TI  - Turribrachycephaly: a technical note.
AB  - We describe a technique for early correction of the so-called towering skull
      deformity, or turribrachycephaly. The technique makes use of the natural
      elasticity and plasticity of cranial bone, and it is best applied during the
      first year of life. Surgery consist of routine exposure of the cranial bone via a
      coronal incision. The frontal bone flap is elevated and removed. On either side,
      a bony osteotomy is then made, commencing low down in the temporal region and
      running posteriorly and superiorly toward the occiput. This approach leaves a
      superior bone flap, which may be left attached to the occipital bone via a
      flexible posterior hinge region, or completely detached by continuing the
      osteotomy across the midline. After the osteotomy, the bone flap is elevated up
      to the sagittal sinus on either side of the midline. The bone flap is not
      removed, but pushed down, compressing the brain along the craniocaudal axis. The
      lateral edge of the flap overlaps the temporal bone, and it can be fixed in the
      desired position by means of simple positional screws or Vicryl sutures. A
      standard fronto-orbital advancement is performed prior to lowering the skull
      vault, which permits the brain to be moved down and forward, filling the dead
      space in the anterior cranial fossa. The frontal bone flap is then shaped
      appropriately and fixed by means of plates and screws to the advanced fronto
      orbital bar. Posteriorly, the frontal lobe is left "floating." To date, we have
      performed this technique on 5 patients, and we find it both faster and simpler
      than other techniques. Short-term results in terms of cranial shape are good. In
      older infants (> 2 years of age), this technique may not prove useful because of
      the loss of the loss of plasticity of the bone.

PMID- 8748347
TI  - Clinical and pathological features of pediatric dermatofibrosarcoma protuberans.
AB  - Dermatofibrosarcoma protuberans (DFSP) is an uncommon malignant mesenchymal tumor
      characterized by local invasion and recurrence. Fewer than 50 cases have been
      reported in the pediatric population. We reviewed our experience in the treatment
      of children with DFSP to define clinical and pathological characteristics. Seven
      pediatric patients were included in the study (mean age, 11.7 yr). Clinically,
      the tumors were described as firm nodules fixed to the skin but mobile over the
      deep fascia, with slow, progressive growth. Diagnosis was made by excisional
      biopsy in 6 patients and punch biopsy in 1 patient. Six of 7 patients had
      positive margins after the diagnostic procedure. Pathologically, diagnosis was
      based on histology, with confirmation by CD34 staining. Definitive surgical
      therapy consisted of wide local excision (1-3 cm margins) in 5 patients and Moh's
      micrographic resection in 2 patients. There have been no local recurrences or
      distant metastases, with a mean follow-up of 15.1 months. Pathological and
      clinical diagnostic criteria for the pediatric population are reviewed, and
      treatment options are discussed.

PMID- 8748348
TI  - Contraction potency of hypertrophic scar-derived fibroblasts in a connective
      tissue model: in vitro analysis of wound contraction.
AB  - Many investigators have reported that collagen gel contraction reflects the
      mechanism of wound contraction. By using a connective tissue model (CTM) of
      collagen gel lattice, we analyzed the contraction potency of fibroblasts that had
      been obtained from hypertrophic scar, normal skin, and normal oral mucosa. We
      then tried to analyze the mechanism of CTM contraction by immunofluorescent
      microscopic and transmission electron microscopic examinations. Hypertrophic scar
      derived fibroblasts in CTM possessed the greatest contraction potency and the
      shortest lag time when compared with those of normal skin and normal oral mucosa
      derived CTMs. It became clear that the initial contractive degree of CTM was
      closely related to morphological changes of fibroblast cells into bipolar and
      elongated shapes. Hypertrophic scar-derived fibroblasts elongated their processes
      faster, and their intracellular actin filaments were more numerous than those of
      normal fibroblasts. We believe that the hypertrophic scar-derived CTM is a useful
      pathological model for the research of wound contraction and hypertrophic scar
      formation.

PMID- 8748349
TI  - Tissue expanders and magnetic resonance imaging: the "hot" breast implant.
AB  - Magnetic resonance imaging (MRI) utilizes three electromagnetic fields to create
      images. Despite these electromagnetic fields and concern for patients with
      metallic implants, studies and clinical experience have demonstrated the safety
      of this modality in the presence of nonferromagnetic implants. However, little
      has been written about the use of MRI scans in patients with tissue expanders. We
      present a case of a woman who developed a burning sensation at the site of her
      tissue expander during an MRI scan. The sensation resolved rapidly once the scan
      was discontinued. The potential for metallic heating or motion within the
      electromagnetic field is discussed. Patients with tissue expanders who require
      MRI scans should be carefully questioned about localized symptoms in the region
      of their expander during the scan. However, the actual implications of the
      symptoms for this group of patients are unclear.

PMID- 8748350
TI  - A late, fatal complication of a high energy thermal injury to the scalp.
AB  - Marjolin's ulcer is an uncommon condition in which malignant transformation
      occurs in a chronic inflammatory focus. It was originally described in
      association with a thermal injury, however, its occurrence with protean chronic
      inflammatory foci has been described. We report the occurrence of and aggressive
      squamous carcinoma 3 decades after a high voltage electric mark injury to the
      scalp. This is the first such case described in the literature. The case
      supportively highlights the role of chronic inflammation and sepsis in epidermal
      scar cancer development, and it underlines the importance of appropriate wound
      management initially and expeditious treatment of sepsis and resistant skin
      ulceration because the malignant behavior of these tumors is aggressive and
      unpredictable.

PMID- 8748351
TI  - A new lunch box-type method in umbilical reconstruction.
AB  - A simple and easy technique for reconstruction of the umbilicus was devised, with
      emphasis on forming walls of the umbilicus and a depression in a caudal
      direction. A quite satisfactory result was obtained. A permanent and sufficient
      depression for the umbilicus can be expected as a result of three-dimensional
      formation of walls.

PMID- 8748352
TI  - Accessory slip of the palmaris longus muscle.
AB  - We discuss the case of a patient presenting an accessory slip of the palmaris
      longus (PL) muscle, which caused symptoms of median nerve compression on his left
      forearm. An asymptomatically anomalous distal PL belly contralaterally is also
      reported, and the clinical relevance and diagnosis of PL anomalies are discussed.

PMID- 8748353
TI  - Subtotal calcanectomy for osteomyelitis of the os calcis: a reasonable
      alternative to free tissue transfer.
AB  - Composite wounds of the heel with secondary secondary osteomyelitis of the
      calcaneus remain a reconstructive challenge. A paucity of regional flaps has
      often necessitated microvascular transplantation in order to obtain wound
      healing. Subtotal calcanectomy, traditionally a technique of the orthopedic
      surgeon, can, in selected cases, eradicate infection and achieve wound closure
      and limb preservation. A review was undertaken of one hospital's experience with
      this procedure over a 4-year period. Five patients with osteomyelitis of the os
      calcis were identified who were successfully managed with subtotal calcanectomy.

PMID- 8748354
TI  - Synovial cell sarcoma of the temporomandibular joint.
AB  - Synovial cell sarcoma is a relatively rare tumor that occurs infrequently in the
      head and neck. Despite the low incidence, synovial cell sarcoma should be a part
      of the differential diagnosis when evaluating masses in the head and neck region.
      The primary mode of treatment is wide en bloc excision. The decision to perform
      lymph node dissections should be based on physical findings or imaging studies
      that suggest lymphadenopathy. Post-operative radiation therapy is believed to be
      of value, but only in large doses of 65 Gy or more. The role of chemotherapy
      remains unclear. Despite recent advances, the prognosis for this disease remains
      poor. This report describes the fourth reported case of synovial cell sarcoma
      involving the temporomandibular joint. The case report details the principles of
      wide excision and adjuvant radiation therapy in the treatment of synovial cell
      sarcoma.

PMID- 8748355
TI  - Indirect documentation of the negative effects of irradiation and neck dissection
      on the internal jugular vein.

PMID- 8748356
TI  - Harry M. Vars Research Award. Increase in lumbar spine bone mineral content in
      patients on long-term parenteral nutrition without vitamin D supplementation.
AB  - BACKGROUND: We had previously shown that short-term withdrawal of vitamin D in
      patients with metabolic bone disease complicating home parenteral nutrition (HPN)
      corrected osteomalacia. We therefore conducted a prospective study of the effect
      of long term withdrawal of vitamin D in patients on home parenteral nutrition.
      METHODS: Baseline measurements of bone mineral content, serum levels of calcium,
      phosphorus, parathormone, 25-OH and 1,25 (OH)2D; urinary calcium; and bone
      mineral density were measured. Then all parenteral vitamin D was withdrawn and
      the above parameters were followed for a mean of 4.5 years. RESULTS: Lumbar spine
      bone mineral content (LSBMC) was 0.79 +/- 0.06 g/cm2 at the start of the study,
      well below the reference value, 1.16 +/- 0.13 g/cm2. Parathyroid hormone (PTH)
      (0.48 +/- 0.24 pmol/L) and 1,25-(OH)2D levels (22.8 +/- 7.9 pmol/L) were low and
      25-hydroxyvitaniin D levels were normal (33.3 +/- 5.5 nmol/L) before removing
      vitandn D from the HPN solutions. After withdrawal of vitamin D for 4.5 +/- 0.2
      years LSBMC increased from 0.79 +/- 0.06 to 0.93 0.07 g/cm2 (p < 0.005). Calcium
      phosphorus, magnesium and 25-hydroxyvitamin D did not change significantly,
      1,25(OH)2D, and PTH levels became normal after withdrawal of vitamin D.
      CONCLUSIONS: In selected patients with depressed PTH levels, long-term withdrawal
      of vitamin D during HPN increases LSBMC and levels of PTH and 1,25(OH)2D. There
      is no reduction of the mean level of 25-hydroxyvitamin D.

PMID- 8748357
TI  - Early enteral nutrition support in patients undergoing liver transplantation.
AB  - BACKGROUND: The purpose of this study was to determine the effects of early
      postoperative tube feeding on outcomes of liver transplant recipients. METHODS:
      Fifty transplant patients were randomized prospectively to receive enteral
      formula via nasointestinal feeding tubes (tube-feeding [TF] group) or maintenance
      i.v. fluid until oral diets were initiated (control group). Thirty-one patients
      completed the study. Resting energy expenditure, nitrogen balance, and grip
      strength were measured on days 2, 4, 7, and 12 after liver transplantation.
      Calorie and protein intakes were calculated for 12 days posttransplant. RESULTS:
      Tube feeding was tolerated in the TF group (n = 14). The TF patients had greater
      cumulative 12-day nutrient intakes (22,464 +/- 3554 kcal, 927 +/- 122 g protein)
      than did the control patients (15,474 +/- 5265 kcal, 637 +/- 248 g protein) (p <
      .002). Nitrogen balance was better in the TF group on posttransplant day 4 than
      in the control group (p < .03). There was a rise in the overall mean resting
      energy expenditure in the first two posttransplant weeks from 1487 +/- 338 to
      1990 +/- 367 kcal (p = .0002). Viral infections occurred in 17.7% of control
      patients compared with 0% of TF patients (p = .05). Although other infections
      tended to occur more frequently in the control group vs the TF group (bacterial,
      29.4% vs 14.3%; overall infections, 47.1% vs 21.4%), these differences were not
      statistically significant. Early posttransplant tube feeding did not influence
      hospitalization costs, hours on the ventilator, lengths of stay in the intensive
      care unit and hospital, rehospitalizations, or rejection during the first 21
      posttransplant days. CONCLUSIONS: Early posttransplant tube feeding was tolerated
      and promoted improvements in some outcomes and should be considered for all liver
      transplant patients.

PMID- 8748358
TI  - Insulin-like growth factor-I enhances immune response in dexamethasone-treated or
      surgically stressed rats maintained with total parenteral nutrition.
AB  - BACKGROUND: New evidence suggests that insulin-like growth factor-I (IGF-I) is an
      important regulator of immune response. Our objective was to determine the
      effects of IGF-I on immune response during total parenteral nutrition (TPN) using
      two stress models. METHODS: Male, Sprague-Dawley rats (230 to 250 g) were given
      TPN with or without coinfusion of recombinant human IGF-I (800 micrograms/d for 6
      days) and subjected to either dexamethasone, a synthetic glucocorticoid, or
      surgical stress, in the form of a midline abdominal incision. In the
      dexamethasone model, immune response was assessed by total cellularity of the
      thymus and spleen, in vitro assays of lymphocyte proliferation, and interleukin 6
      (IL-6) production, and concentrations of IL-6 and tumor necrosis factor alpha
      (TNF-alpha) in serum. In the surgical model, flow cytometry was used to identify
      and quantify splenic populations of T and B lymphocytes and macrophages. RESULTS:
      In rats immunosuppressed by dexamethasone, IGF-I infusion increased mitogen
      induced proliferation of thymocytes, but did not alter cellularity in the thymus;
      enhanced proliferation and IL-6 production in peripheral blood mononuclear cells
      following treatment with concanavalin A or lipopolysaccharide; and reduced the
      serum concentration of IL-6, but not TNF-alpha. In surgically stressed rats, IGF
      I infusion restored the splenic populations of immature and mature B lymphocytes,
      which were decreased by TPN. CONCLUSIONS: our data demonstrate that IGF-1
      enhances immune response during TPN in rats.

PMID- 8748359
TI  - Parenteral nutrition is associated with intestinal morphologic and functional
      changes in humans.
AB  - BACKGROUND: Numerous animal studies have demonstrated intestinal villus atrophy
      occurs when luminal nutrition is withheld and total parenteral nutrition (TPN) is
      provided. Intestinal morphologic and functional changes have not been well
      studied in humans during TPN. METHODS: Eight normal volunteers were hospitalized
      in the Clinical Research Center for 3 weeks. The subjects received TPN as an
      exclusive means of nutritional support for 14 days followed by 5 days of enteral
      refeeding with either a standard or a glutamine and arginine-supplemented
      formula. Endoscopic jejunal biopsies were taken before and after TPN and after
      enteral refeeding. Intestinal morphology was examined by light and transmission
      electron microscopy. Mucosa DNA, RNA, and protein concentrations were measured.
      Lactose breath hydrogen and intestinal permeability testing (urinary lactulose
      and mannitol excretion after an oral dose) were performed before and after TPN
      and after enteral refeeding. RESULTS: Total mucosal thickness decreased after TPN
      (645 +/- 19 to 512 +/_ 19 microns, p = .003) and increased significantly towards
      baseline after enteral refeeding (575 +/- 19 microns, p = .04). The change was
      related solely to villus height; crypt depth was unaffected. Villus cell count
      decreased from 179 +/- 15 to 163 +/- 12 after TPN (p = .03) and increased after
      enteral refeeding to 176 +/- 21 (p = .06). Crypt cell count was unaffected by TPN
      or refeeding. A nonsignificant decrease in the mitotic index after TPN was seen.
      Intracellular edema developed during TPN and resolved with enteral refeeding. The
      urinary lactulose-mannitol ratio increased with TPN [0.06 +/- 0.03 to 0.11 +/-
      0.05 after TPN and 0.14 +/_ 0.09 after short-term enteral refeeding (p = .05)],
      indicating increased intestinal permeability. The urinary lactulose-mannitol
      ratio was significantly greater after refeeding with standard formula than the
      free amino acid peptide formula with glutamine and arginine (0.20 +/- 0.05, vs
      0.08 +/- 0.01, p = .05). No significant differences were noted in mucosal RNA,
      DNA, protein, DNA-protein or RNA-DNA rations or breath hydrogen after lactose
      ingestion after either TPN or enteral refeeding. No significant difference in
      plasma glutamine was found during TPN (462.7 +/ 38.7 vs 491.8 +/- 46.1 mumol/L)
      or after enteral refeeding (457.3 +/- 51.4 mumol/L). CONCLUSIONS: Intestinal
      morphologic and functional changes occur in human for whom TPN is the sole
      nutritional source, although the findings in humans are substantially less
      significant than observed in animal models. The loss of mucosal structure may be
      sufficient to cause increased intestinal permeability, the clinical significance
      of which remains to be defined. Enteral nutrition is important in restoring and
      probably preventing morphologic intestinal changes associated with TPN, and a
      peptide and free amino acid-based formula supplemented with glutamine and
      arginine may have some added role. Our findings also suggest sepsis is associated
      with gut adaptation rather than degradation.

PMID- 8748360
TI  - Dietary long-chain polyunsaturated fatty acids influence the recovery of
      thioacetamide-induced liver cirrhosis in rats.
AB  - BACKGROUND: The aim of this study was to evaluate the dietary supplementation
      with omega-3 and omega-6 long-chain polyunsaturated fatty acids on the fatty acid
      composition of plasma and red blood cell membranes in rats with thioacetamide
      induced liver cirrhosis. METHODS: Thirty-eight female Wistar rats were given 300
      mg thioacetamide/L in drinking water for 4 months to induce the experimental
      liver cirrhosis. Sixteen rats were used as controls. After treatment with
      thioacetamide, nine rats of each group were killed. Then, thioacetamide-treated
      rats were divided into three new groups, each receiving a different diet for 2
      weeks: a semipurified diet (n = 9), the same diet supplemented with omega-3 long
      chain polyunsaturated fatty acids (n = 10), or the same semipurified diet
      supplemented with omega-3 and omega-6 long-chain polyunsaturated fatty acids
      simultaneously (n = 10). The remaining control rats were fed the semipurified
      diet. Liver histology and plasma and erythrocyte fatty acid composition were
      assessed. RESULTS: An apparent improvement of the histological damage took place
      in the rats fed the omega-3+ omega-6-supplemented diet. The diet supplemented
      with polyunsaturated fatty acids of the omega-3 series induced increases in the
      omega-3 long-chain polyunsaturated fatty acid levels in total plasma lipids,
      plasma lipid fractions and in erythrocyte phospholipids, and decreases in omega-6
      long-chain polyunsaturated fatty acids in erythrocyte phospholipids during the
      recovery of rats with thioacetamide-induced liver cirrhosis. The administration
      of the diet supplemented with both omega-3 and omega-6 long-chain polyunsaturated
      fatty acids contributed to increase the levels of total plasma saturated,
      monounsaturated, and omega-6 long-chain polyunsaturated fatty acids from
      cirrhotic rats. CONCLUSION: We conclude that the simultaneous supply of long
      chain fatty acids of the omega-3 and the omega-6 series can be beneficial to
      improve the fatty acid status of this experimental model of liver cirrhosis.

PMID- 8748361
TI  - Glutamine supplementation of enteral nutrition: impact on whole body protein
      kinetics and glucose metabolism in critically ill patients.
AB  - BACKGROUND: Glutamine-supplemented parenteral nutrition has been reported to
      attenuate the early postoperative reduction in intracellular glutamine and
      improve protein synthesis and nitrogen balance. We investigated the effect of an
      enteral formula or protein and glucose kinetics and nitrogen balance in trauma
      patients. METHODS: The enteral formula (AlitraQ) provided a mean intake of 0.35 g
      of glutamine/kg body weight per day to 16 trauma patients and was compared with
      an isonitrogenous formula that provided a mean of 0.05 g of glutamine/kg body
      weight per day in 14 trauma patients. After 3 days of feeding, protein kinetics
      were measured using a 4-hour prime-continuous infusion of L-[1-13C]leucine.
      Glucose kinetics were measured during the same time interval using prime
      continuous infusion of [U-14C]- and [6-3H]glucose. RESULTS: Nitrogen balance was
      not significantly different in the two groups. There were no significant
      differences in protein turnover, synthesis, and breakdown between the two groups.
      There were no significant differences in glucose turnover, oxidation, recycling,
      and percent of VCO2 from glucose oxidation between the two groups. CONCLUSIONS:
      Glutamine-enriched enteral formulas are well tolerated by the severely injured
      patient but provide no additional nutritional advantage compared with standard
      enteral formulas during the first 3 days of feeding immediately after trauma.

PMID- 8748362
TI  - Inhibition of pulmonary microvascular endothelial glutamine transport by
      glucocorticoids and endotoxin.
AB  - BACKGROUND: During septic states, the lungs produce increased amounts of
      glutamine, an event that is mediated by both endotoxin and glucocorticoid
      hormones and is presumed to be due to accelerated intracellular glutamine
      biosynthesis. Because enhanced net glutamine release in vivo could also be due to
      a decrease in cellular uptake, we assayed glutamine transport in cultured rat
      microvascular pulmonary endothelial cells. METHODS: The effect of Escherichia
      coli endotoxin (LPS, 1 microgram/mL), various cytokines, and dexamethasone (DEX,
      0.1 mumol/L) on glutamine transport activity was studied in rat lung
      microvascular endothelial cells grown in varying glutamine concentrations (0,
      0.1, 0.5, and 2 mmol/L). Experiments were also performed in cells treated with
      cycloheximide, actinomycin D, or chelerythrine chloride. RESULTS: More than 90%
      of glutamine transport was mediated by the Na+ -dependent transport system ASC.
      DEX and LPS inhibited endothelial glutamine uptake in a time- and dose-dependent
      manner, a response that was only observed with incubation medium contained the
      lower concentrations of glutamine. Neither DEX nor LPS altered transport activity
      in cells cultured in medium containing 2 mmol glutamine/L. There was no
      synergistic or additive effect when both compounds were added together. The
      cytokines tumor necrosis factor alpha, interleukin (IL) 1, IL-2, and IL-6 did not
      alter glutamine transport. both DEX and LPS inhibited glutamine transport by
      decreasing transporter maximal transport velocity (Vmax) without affecting
      transporter affinity (Km). Cycloheximide and actinomycin D abrogated the
      inhibition of transport activity that was observed in DEX- or LPS-treated cells,
      whereas the protein kinase C inhibitor chelerythrine chloride had no effect on
      either control or stimulated glutamine transport. CONCLUSIONS: These data suggest
      that DEX and LPS "down-regulate" glutamine uptake by lung microvascular
      endothelial cells by inducing the synthesis of an inhibitory protein that
      modulates the activity of the system ASC protein. This response in vitro appears
      to be influenced by the extracellular glutamine concentration. This decrease in
      microvascular endothelial glutamine transport may be one mechanism by which net
      lung glutamine release is enhanced during critical illness.

PMID- 8748363
TI  - Improved clinical status and length of care with low-fat nutrition support in
      burn patients.
AB  - BACKGROUND: The optimal amount and type of fat in the nutrition support of burned
      patients have not been determined. The aim of this study was to test low-fat
      nutritional solutions, with or without fish oil, on protein metabolism,
      morbidity, and length of care in severely burned adults. METHODS: In a
      prospective randomized clinical trial, 43 patients were assigned to one of the
      following groups: control (35% fat), low-fat solution (ie, 15% of total calories
      as fat), low-fat with fish oil, given for 30 days. Nitrogen balance, urinary 3
      methylhistidine excretion, urinary cortisol, and clinical status were measured
      daily. Corticosteroid-binding globulin and total and free serum cortisol were
      measured every 3 days. RESULTS: Compared with controls, patients on low-fat
      support had fewer cases of pneumonia: 3/24 vs 7/13 (p = .02), better respiratory
      and nutrition status, and shorter time to healing: 1.2 vs 1.8 days/% burned area
      (p = 0.01). There was no difference in nitrogen balance between groups, and 3
      methylhistidine excretion was higher and serum free cortisol was lower in log-fat
      -fed patients than in controls. There was no difference between the two low-fat
      groups in any of the parameters measured. CONCLUSIONS: This study showed that low
      fat nutrition support decreases infectious morbidity and shortens length of stay
      in burn patients. Fish oil does not seem to add clinical benefit to low-fat
      solutions. In addition, this study provides the first evidence that nutrition
      intervention modulates cortisol-binding globulin and the concentration of free
      circulating cortisol after a severe stress.

PMID- 8748364
TI  - Effect of glutamine supplementation on protein metabolism and glutathione in
      tumor-bearing rats.
AB  - BACKGROUND: Since tumor-bearing rats are deficient in glutamine, we investigated
      whether (1) glutamine and glutathione deficiency occur in tumor-bearing rats, (2)
      glutamine supplementation caused an increase of glutathione levels in host
      tissues and tumor, (3) glutamine enhances protein synthesis in host tissues, and
      (4) glutamine stimulated the tumor to synthesize protein and DNA. METHODS: Male
      Donryu rats were randomized into four groups: (1) non-tumor-bearing rat (NTB) +
      standard total parenteral nutrition (STPN); (2) NTB + glutamine-supplemented TPN
      (GTPN); (3) tumor-bearing rat (TB) + STPN; (4) TB + GTPN. On day 0 AH109A rat
      hepatoma cells were subcutaneously injected into the backs of rats to induce
      tumor. The animals were maintained on TPN for 6 days from day 10 through day 15.
      On day 15, 1-14C-leucine was given by a 5-hour continuous infusion (2.0 microCi/h
      per rat) to determine the fractional synthesis rate and endogenous leucine
      production. The levels of glutamine and glutathione were measured by HPLC. the
      tumor DNA synthesis was estimated by bromodeoxyuridine labeling index. RESULTS:
      Tumor development led to a significant weight loss, but this weight loss was
      significantly lessened by glutamine supplementation because of an increase in
      muscle protein synthesis. Glutamine did not enhance tumor weight, protein, and
      DNA synthesis in the tumor. Tumor development caused a significant reduction of
      glutathione in the muscle, jejunum, and liver, but supplemented glutamine
      increased the levels of glutathione in the jejunum. CONCLUSION: Glutamine
      supplementation is beneficial in preventing deficiencies of glutamine and
      glutathione and in improving protein metabolism in tumor-bearing rats.

PMID- 8748365
TI  - Pharmacokinetic analysis of dodecanedioic acid in humans from bolus data.
AB  - BACKGROUND: Excretion and tissue uptake of dodecanedioic acid (C12), a proposed
      alternative fuel substrate, was investigated in humans by bolus experiments.
      METHODS: Seven overnight-fasting healthy male volunteers received i.v. a bolus (1
      g) of C12. Blood samples were collected after C12 administration at intervals of
      15 minutes, and C12 serum concentration was measured by high-performance liquid
      chromatography. C12 excretion in 24-hour urine was measured. Binding of C12 in
      human serum was determined in separate equilibrium dialysis experiments by means
      of an isotopic compound (disodic salt of (1,12)14C-dodecanedioic acid). A two
      compartment model was used for describing C12 kinetics. RESULTS: The excreted
      amount of C12 in 24-hour urine was found to be, on the average, 1.62% of
      administered dose. The apparent number of binding sites per albumin molecule was
      3.1 +/- 0.2 (estimate +/- SE) with an affinity constant of 6.4 +/- 1.8 mM-1. The
      distribution volume of central compartment was 5.56 +/- 3.13 L and that of
      peripheral compartment was 87.4 +/- 30.4 L. The rate constant of exchange between
      compartments was 4.60 +/- 3.50 L/min, that or urinary excretion 25.6 +2- 15.5
      mL/min, and that of tissue uptake 2.17 +/- 0.86 L/min. CONCLUSIONS: These results
      are promising for C12 utilization in parenteral nutrition, because C12
      elimination in urine is low whereas tissue uptake appears to be rather efficient.

PMID- 8748366
TI  - Glutamine dipeptide-supplemented parenteral nutrition reverses gut atrophy,
      disaccharidase enzyme activity, and absorption in rats.
AB  - BACKGROUND: Total parenteral nutrition (TPN) is associated with intestinal
      atrophy and dysfunction possibly attributed to the absence of the nonessential
      amino acid glutamine from commercially available TPN solutions because of the
      instability of the monoamino acid during heat sterilization and storage. The use
      of stable dipeptides may overcome this problem. In this study we tested the
      hypothesis that glutamine dipeptide supplementation with alanyl-L-glutamine
      during TPN for 10 days would reverse small bowel atrophy and TPN-induced
      dysfunction in rats. METHODS: A conventional TPN solution (250 kcal/kg bw) was
      compared with an isocaloric and isonitrogenous TPN supplemented with alanyl-L
      glutamine dipeptide. A food-fed control group was included (n = 6 each group).
      Jejunum mucosal architecture, absorption of water and glucose, and disaccharidase
      activity of maltase and alkaline phosphatase were evaluated. RESULTS: TPN-induced
      villous atrophy, significantly reduced absorption rate, and decreased activity of
      villous enzymes, compared with the TPN group, could be reversed by
      supplementation of glutamine dipeptide alanyl-L-glutamine to parenteral nutrition
      solutions with no difference to the control group. CONCLUSIONS: Glutamine
      dipeptide-enriched parenteral nutrition preserves mucosal structure and reversed
      atrophy-associated dysfunction.

PMID- 8748367
TI  - Do heparin, hydrocortisone, and glyceryl trinitrate influence thrombophlebitis
      during full intravenous nutrition via a peripheral vein?
AB  - The aim of this prospective, randomized study was to determine if the addition of
      heparin and hydrocortisone, and the application of a topical glyceryl trinitrate
      patch over the catheter site (triple therapy) would results in a reduced
      incidence of thrombophlebitis during i.v. nutrition through a peripheral vein.
      Forty-six patients were randomized to receive either standard i.v. nutrition
      (i.v.N)(1200 mosm/kg) (control group, n = 23), or i.v.N plus triple therapy
      (study group, n = 23). The patient's arm was examined daily, and the catheter was
      removed if signs of thrombophlebitis were evident. The two groups were well
      matched in terms of age and gender, as well as indication for feeding and total
      days of i.v.N supplied. The catheters in the study group survived longer (p <
      .0001), and resulted in a lower incidence of thrombophlebitis (p < .05). The time
      of onset of thrombophlebitis was delayed in the study group (p < .0001). It is
      recommended that heparin, hydrocortisone, and a glyceryl trinitrate patch should
      be administered to all patients receiving i.v. nutrition via a fine-bore
      peripheral catheter.

PMID- 8748368
TI  - Developmentally regulated expression of a cell surface protein, neuropilin, in
      the mouse nervous system.
AB  - Neuropilin (previously A5) is a cell surface glycoprotein that was originally
      identified in Xenopus tadpole nervous tissues. In Xenopus, neuropilin is
      expressed on both the presynaptic and postsynaptic elements in the visual and
      general somatic sensory systems, suggesting a role in neuronal cell recognition.
      In this study, we identified a mouse homologue of neuropilin and examined its
      expression in developing mouse nervous tissues. cDNA cloning and sequencing
      revealed that the primary structure of the mouse neuropilin was highly similar to
      that of Xenopus and that the extracellular segment of the molecule possessed
      several motifs that were expected to be involved in cell-cell interaction.
      Immunohistochemistry and in situ hybridization analyses in mice indicated that
      the expression of neuropilin was restricted to particular neuron circuits.
      Neuropilin protein was localized on axons but not on the somata of neurons. The
      expression of neuropilin persisted through the time when axons were actively
      growing to form neuronal connections. These observations suggest that neuropilin
      is involved in growth, fasciculation, and targeting for a particular groups of
      axons.

PMID- 8748369
TI  - Chick sensory neuronal growth cones distinguish fibronectin from laminin by
      making substratum contacts that resemble focal contacts.
AB  - The adhesive interactions of nerve growth cones stabilize elongating nerve fibers
      and mediate transmembrane signaling to regulate growth cone behaviors. We used
      interference reflection microscopy and immunocytochemistry to examine the
      dynamics and composition of substratum contacts that growth cones of chick
      sensory neurons make with extracellular adhesive glycoproteins, fibronectin and
      laminin. Interference reflection microscopy indicated that sensory neuronal
      growth cones on fibronectin-treated substrata, but not on laminin, make contacts
      that have the appearance and immobility of fibroblastic focal contacts.
      Interference reflection microscopy and subsequent immunocytochemical staining
      showed that beta 1 integrin and phosphotyrosine residues were concentrated at
      growth cone sites that resemble focal contacts. Two other components of focal
      contacts, paxillin and zyxin, were also co-localized with concentrated
      phosphotyrosine residues at sites that resemble focal contacts. Such staining
      patterns were not observed on laminin-treated substrata. Growth cone migration on
      fibronectin-treated substrata was inhibited by herbimycin A, a tyrosine kinase
      inhibitor. We conclude that sensory neuronal growth cones distinguish fibronectin
      from laminin by making contacts with distinct organization and regulation of
      cytoskeletal components at the adhesive sites. This finding suggests that growth
      cone interactions with different adhesive molecules lead to distinctive
      transmembrane organization and signaling to regulate nerve fiber elongation.

PMID- 8748370
TI  - Ag, a novel protein secreted from Aplysia glia.
AB  - We have isolated a cDNA (ag for Aplysia glial) corresponding to an mRNA specific
      to the nervous system of Aplysia californica. In this study, we characterized the
      ag cDNA sequence and the distribution of ag mRNA and protein in the Aplysia
      nervous system. The ag cDNA contains an open reading frame that encodes a novel
      29 kD protein. In situ hybridizations demonstrate that ag mRNA is conspicuously
      absent from the cell bodies of the large neurons constituting the external layer
      of the ganglia. Instead, it is largely confined to a subset of small, apparently
      non-neuronal cells surrounding the neurons at the border of the neuropil, is
      sparsely scattered within the neuropil, and is widespread within the connective
      nerves, a pattern consistent with glial localization. Polyclonal anti-ag
      antiserum recognizes a protein between 27 and 29 kD that is more broadly
      distributed, especially within the neuropil. The distributions of ag mRNA and
      protein, together with the presence of a putative signal peptide, suggest that ag
      protein is secreted. Two findings support this hypothesis: first, ag protein is
      detectable by western blot in Aplysia hemolymph. Second, full length ag protein
      expressed in COS cells is secreted, but ag lacking the putative signal peptide is
      not. Secretion from glia raises the possibility that this abundant protein may
      affect neighboring neurons.

PMID- 8748371
TI  - Enhancement by serotonin of the growth in vitro of antennal lobe neurons of the
      sphinx moth Manduca sexta.
AB  - Cell culture experiments have been used to examine the effects of serotonin [5
      hydroxytryptamine (5-HT)] on the morphological development of antennal lobe (AL)
      neurons in the brain of the sphinx moth, Manduca sexta. The majority of cells
      used in this study were from animals at stage 5 of the 18 stages of metamorphic
      adult development. 5-HT did not affect the survival of M. sexta AL neurons in
      culture, but did increase the numbers of cells displaying features characteristic
      of certain cell types. Three morphologically distinct cell types were examined in
      detail. The principal effect of 5-HT on these neurons was enhancement of cell
      growth. The magnitude of responses to this amine was cell-type specific. Site
      specific responses to 5-HT were apparent also in one cell type. Our results
      suggest that the effects of 5-HT can change during the course of metamorphic
      development. These changes coincide temporally with the development of fast,
      sodium-based action potentials.

PMID- 8748372
TI  - Spatiotemporal pattern of retinal ganglion cell differentiation revealed by the
      expression of neurolin in embryonic zebrafish.
AB  - The expression of neurolin, the fish homologue of the cell adhesion molecule DM
      GRASP/BEN/SC-1, is dynamically regulated. Here we demonstrate that the expression
      of neurolin correlates with early events of retinal ganglion cell (RGC)
      differentiation in zebrafish embryos. Neurolin mRNA first appears [28 h
      postfertilization, (PF)] in nasoventral cells, representing the first RGCs, then
      in dorsal, central (34 to 40 h PF) and temporal RGCs. After differentiation of
      RGCs in the central portion of the retina, RGCs exhibiting neurolin mRNA form
      rings. These rings move toward the retinal periphery and encompass older
      (central) RGCs. Thereafter, such as at 3.5 days PF, neurolin mRNA expressing RGCs
      are confined to the annular growth zone at the retinal peripheral margin. Two
      hours after onset of mRNA expression, RGCs acquire antineurolin immunoreactivity
      on the surface of their somata and on their axons as they extend to the tectum.
      The mRNA signal in RGCs decreases significantly within 20 h after its appearance,
      which correlates with the arrival of axons in the tectum. This is followed by
      weakening of neurolin immunoreactivity on RGCs and axons. This pattern of RGC
      differentiation in zebrafish revealed by the expression of neurolin is unique
      among vertebrates. The spatiotemporal expression pattern of neurolin suggests a
      functional significance of this cell adhesion molecule in RGC recognition and RGC
      axon growth.

PMID- 8748373
TI  - Rapid activity-dependent sprouting of optic fibers into a local area denervated
      by application of beta-bungarotoxin in goldfish tectum.
AB  - The retinotectal projection is known to be capable of extensive long-term
      expansion of connections, but it is not known how fast such changes can occur or
      what triggers sprouting of terminals. We studied sprouting of optic fibers into
      an area denervated by local microinjection of beta-bungarotoxin (beta-BTX), a
      specific presynaptic neurotoxin with phospholipase A2 activity that destroys
      nerve terminals at the neuromuscular junction. After injection of 0.1 pmol of
      beta-BTX, the optic terminals fired spontaneously with decreasing amplitude and
      became silent within 1 to 2 h. Outside the injection zone, the retinotectal map
      was normal, so the silent zone was associated with a scotoma in the visual field.
      Horseradish peroxidase (HRP) staining of the entire optic nerve showed a
      denervated region at the injection site with beaded, degenerating fibers at its
      edge. Between 3 and 9 days later, optic units were recorded within the injection
      zone whose receptive fields lay just outside the scotoma in the visual field,
      indicating that intact surrounding terminals had sprouted into the area. These
      sprouts made functional connections, as indicated by field potential recordings
      and current source-density analysis. At this time, HRP staining also demonstrated
      retinal innervation within the injection zone. By 12 days, normal maps with no
      scotoma were recorded and HRP staining was normal at the injection site,
      indicating that the beta-BTX-damaged fibers had regenerated to reclaim their
      tectal sites. The results show that the retinotectal projection of goldfish is
      very dynamic, since intact optic fibers can sprout into adjacent vacant
      postsynaptic territory within 2 to 3 days, much faster than previously reported.
      In a final experiment, we showed that this sprouting is activity-dependent, since
      it could be prevented by blocking retinal activity with intraocular tetrodotoxin
      (TTX) during the first 2 days postinjection, even though TTX block of activity
      does not block regeneration in this system. One possible mechanism for this
      rapidly triggered sprouting is that arachidonic acid liberated by beta-BTX acts
      as a sprouting factor to attract surrounding healthy fibers into the denervated
      region but requires activity at the terminals to be effective.

PMID- 8748374
TI  - Neurogenesis of the sexually dimorphic vasopressin cells of the bed nucleus of
      the stria terminalis and amygdala of rats.
AB  - The bed nucleus of the stria terminalis (BNST) and centromedial amygdala share
      many neuroantomical and neurochemical characteristics, suggesting similarities in
      their development. Here we compare the neurogenesis of a group of cells for which
      already several common characteristics have been documented, that is, the
      sexually dimorphic arginine vasopressin-immunoreactive (AVP-ir) cells of the BNST
      and amygdala. To determine when these cells are born, pregnant rats received
      intraperitoneal injections of the thymidine analogue bromo-2-deoxy-5-uridine
      (BrdU) on one of nine embryonic days, E10 to E18; E1 being the day that a
      copulatory plug was found. At 3 months of age, the offsprings of these females
      were killed and their brains stained immunocytochemically for BrdU and AVP. Most
      AVP-ir cells were labeled with BrdU by injections on E12 and E13. Although BrdU
      labeling of AVP-ir cells did not differ between the BNST and amygdala, it
      differed between males and females. From E12 to E13, the percentage of BrdU
      labeled AVP-ir cells decreased more in males than in females. AVP-ir cells
      appeared to be born earlier than most other cells in the same area, the majority
      of which were labeled with BrdU by injections on E14, E15, and E16. The
      similarities in the birthdates of AVP-ir cells in the BNST and amygdala may help
      to explain why these cells take on so many similar characteristics. The sex
      difference in birthdates of AVP-ir cells may help to explain which cellular
      processes underlie the sexual differentiation of these cells.

PMID- 8748375
TI  - Developmental plasticity of neuropeptide expression in motoneurons of the moth,
      Manduca sexta: steroid hormone regulation.
AB  - Developmental changes in the expression of a FMRFamide-like (Phe-Met-Arg-Phe-NH2)
      peptide or peptides in motoneurons of the tobacco hornworm, Manduca sexta, were
      demonstrated using immunohistochemical techniques. The onset of FMRFamide-like
      immunoreactivity (FLI) was gradual during larval growth but by the final larval
      stage, immunoreactivity was present in the majority of motoneurons. FLI then
      declined during metamorphosis and was absent in all identified adult motoneurons.
      We used a novel in vivo culture system to demonstrate that the steroid hormone,
      20-hydroxyecdysone, regulates the loss of FLI in motoneurons during
      metamorphosis. The small commitment peak of ecdysteroid appears to shut off the
      program of neuropeptide accumulation that is characteristic of the larval state
      of the motoneurons. The prepupal peak of steroid then causes the rapid loss of
      stored FLI. This steroid-induced change in the neuropeptide content of
      motoneurons may reflect major changes in neuromuscular functions between the
      larval and adult stages.

PMID- 8748376
TI  - Post-translational regulation of neuronal acetylcholine receptors stably
      expressed in a mouse fibroblast cell line.
AB  - Second messenger regulation of neuronal acetylcholine receptors (AChRs) was
      investigated in a mouse fibroblast cell line, M10, stably transfected with
      chicken alpha 4 and beta 2 cDNAs. Both forskolin and 8-bromo-cyclic adenosine
      3',5'-monophosphate (cAMP) induced large increases in the numbers of AChRs. The
      increases were due in part to increased transcription and translation of the
      alpha 4 and beta 2 genes. Blockade of protein synthesis with cycloheximide,
      however, revealed that forskolin also exerts a post-translational effect,
      increasing the number of surface receptors by twofold. Immunoblot analysis of
      sucrose gradient fractions confirmed that the cells had a large fraction of
      unassembled subunits potentially available for receptor assembly. The post
      translational effect of forskolin was blocked by H-89, an inhibitor of cAMP
      dependent protein kinase, and by okadaic acid, an inhibitor of phosphatases 1 and
      2A. Nicotine also acted post-translationally to induce a twofold increase in the
      number of surface receptors, but the mechanism differed from that utilized by
      forskolin, since the effects of the two agents were additive and were
      differentially affected by okadaic acid. The results suggest that protein
      phosphorylation-dephosphorylation mechanisms act post-translationally to increase
      the number of neuronal AChRs maintained on the cell surface. This could be
      achieved by increasing the efficiency of receptor assembly, transport, or
      stabilization on the cell surface.

PMID- 8748377
TI  - The neurobiology of anxiety disorders.
AB  - The use of pharmacologic challenges and the application of new brain imaging
      technologies in the study of patients with anxiety disorders have led to an
      improvement in the understanding of the neurobiologic basis of these disorders.
      Abnormal function of noradrenergic, serotonergic, GABAergic, and dopaminergic
      neural systems as well as abnormal chemoreceptor reactivity have all been
      implicated in the pathophysiology of anxiety. Functional imaging data have
      revealed abnormal patterns of cortical and subcortical activity in anxiety
      patients. These data have allowed significant improvements in the available
      anatomic models of the anxiety disorders. Further improvements in research
      technique and technology likely will lead in the near future to a significantly
      clearer image of the neurobiologic processes involved in anxiety disorders.

PMID- 8748378
TI  - Primate models of anxiety. Longitudinal perspectives.
AB  - In summary, VFD subjects appear to have sustained long-term behavioral and
      biologic sequelae following disruption of normative maternal-infant attachment
      patterns. The sequelae are primarily manifest as stable anxiety or affective
      traits and, from a biologic perspective, are most analogous to recent data that
      have emerged from studies of patients with PTSD. Multiple abnormalities are
      observed of systems directly involved in affect regulation. Further studies are
      required to clarify the pathologic ontogeny of the VFD condition and its
      potential relevance to human psychopathology.

PMID- 8748379
TI  - Anxiety disorders of childhood, Implications for adult psychopathology.
AB  - Although the exact path of acquisition remains incompletely understood, research
      supports the association between anxiety disorders in children and
      psychopathologic conditions in adults. This article addresses this relationship;
      reviews findings on the temperamental profile and behavioral inhibition, which
      may be an early identifiable childhood predictor of later anxiety disorders; and
      discusses the importance of early intervention.

PMID- 8748380
TI  - Treatment of anxiety disorders of childhood.
AB  - The development of empirically derived, efficacious treatment methods for the
      range of anxiety disorders in children and adolescents lags far behind the field
      of adult anxiety treatment research. Controlled trials of both psychosocial and
      pharmacologic methods are warranted, and several trials are currently underway.
      Although the literature in this field is growing, many questions remain regarding
      the application and long-term benefit of interventions with youth. Specifically,
      although the field of adult psychosocial treatment research has advanced such
      that empirically derived treatment protocols are readily available, such
      methodologies are lacking for anxious youth. Serious attention must turn toward
      the empirical testing and validation of developmentally appropriate psychosocial
      treatment protocols. Fortunately, work in this area is currently under way in
      several centers (e.g., for social phobia, OCD, and generalized anxiety).
      Moreover, the role of parents in the psychosocial treatment process remains
      largely unexplored. Investigations are underway examining the effectiveness of
      training parents in the delivery of particular psychosocial procedures and
      evaluating the optimal "degree" of parental involvement. Attention also must turn
      to the systematic study of variables hypothesized to affect negatively the
      successful integration of parents (e.g., age of child, severity of disorder,
      parental psychopathology). And lastly, combined trials of pharmacologic compounds
      and psychosocial interventions are needed to examine the prescriptive treatment
      approach of matching patients to treatments.

PMID- 8748381
TI  - The longitudinal course and outcome of panic disorder.
AB  - Converging lines of evidence from a variety of methods of inquiry support a
      developmental model for panic disorder that includes a constitutional
      predisposition for anxiety influenced by genetic, familial, cognitive-behavioral
      and psychosocial factors, early expression during childhood, and variable
      manifestations during the life-cycle. Studies of patients followed up after acute
      pharmacotherapy trials and those treated naturalistically are consistent with
      this model and portray panic disorder as a generally chronic condition with a
      longitudinal course marked by relatively brief intervals of remission and high
      rates of recurrence and relapse. Longitudinal and follow-up studies suggest that
      panic attack frequency responds more readily and rapidly to pharmacotherapy than
      do other aspects of panic disorder such as agoraphobia and generalized anxiety.
      In general, the presence of agoraphobia is associated with more severe symptoms,
      greater chronicity, and more limited response to treatment. Other variables
      associated with chronicity and treatment resistance include patient-related
      factors (psychiatric and medical comorbidity, anxiety sensitivity) and
      pharmacologic factors (adequacy of dose, duration, and compliance). Although it
      is currently difficult to predict the duration of treatment needed for an
      individual patient, available evidence suggests that a substantial proportion of
      patients may require chronic treatment for panic disorder.

PMID- 8748382
TI  - Cognitive-behavior therapy and the longitudinal course of panic disorder.
AB  - This article examines the nature and course of panic disorder as understood from
      a cognitive-behavioral perspective. A model of the causes and maintenance of
      panic disorder is presented, and is followed by a discussion of the elements and
      efficacy of cognitive-behavioral treatment. Treatment effects and factors
      associated with relapse are considered within the context of evidence for a
      differential course of panic disorder for patients treated with cognitive
      behavioral therapy relative to those treated with pharmacotherapy. Issues of
      combined treatment, maintenance of treatment gains, and preventive interventions
      are discussed.

PMID- 8748383
TI  - Social phobia. Longitudinal course and long-term outcome of cognitive-behavioral
      treatment.
AB  - Interest in social phobia has increased dramatically in the past decade, and our
      knowledge of this previously understudied disorder has increased as well. We now
      know that social phobia is a chronic condition and that patients with this
      disorder are unlikely to experience significant improvement without intervention.
      It is also a highly prevalent condition affecting as many as 13% of the adult
      population of the Unites States. Although our understanding of the causes of
      social phobia remains limited, we do know that it is associated with serious
      impairment and disability in multiple spheres. Thus, the development of
      treatments with proven long-term efficacy is an important research goal. In this
      article, we have reviewed studies that examined either exposure, cognitive
      restructuring, social skills training, or some combination of these treatments.
      Here, we summarize the major findings of this review. Exposure has fared well as
      a treatment for social phobia and, in every case, within-group analyses show that
      patients have improved after treatment. Methodologic problems in some studies,
      however, limit the conclusions that can be drawn about the comparative efficacy
      of exposure, social skills training, and relaxation therapy. Conceptual models of
      social phobia have stressed the importance of cognitive processes in the
      development and maintenance of social phobia and much attention has been directed
      at the long-term efficacy of cognitive-behavioral techniques. It has been
      hypothesized that exposure plus cognitive restructuring would be a particularly
      effective combination and several methodologically sound studies have examined
      this combination. These studies have demonstrated consistently clinically
      significant within-group changes and superiority to control conditions.
      Heimberg's CBGT is probably the most widely studied of these treatments. CBGT has
      been shown to be more effective than an equally credible attention-placebo group.
      Patients receiving CBGT have maintained their advantage over patients in the
      attention-placebo group, even 5 years after treatment although flaws in that
      follow-up study limit generalizability of its results. Generalized and
      nongeneralized social phobic patients respond equivalently to this highly
      integrated treatment, and it has been applied effectively by researchers outside
      the center where it was developed. Despite the successes of combined exposure and
      cognitive restructuring treatments, it remains unclear as to what the effective
      component(s) of these and similar treatments are and, therefore, whether or not
      the integration of therapy components is really necessary. A number of the
      studies reviewed addressed this question with mixed results. Three studies showed
      that the combination therapy was superior to either treatment alone. There is
      also evidence that patients treated with exposure only may show some
      deterioration during follow-up whereas patients treated with cognitive
      restructuring and exposure may continue to improve. Still, other studies found no
      differences in long-term outcome among exposure alone, RET, or the combined
      treatment. Hope et al found that exposure alone was as effective as an integrated
      treatment combining exposure and cognitive restructuring (CBGT), and Taylor and
      colleagues (submitted for publication, 1995) reported that exposure was not
      enhanced by initial treatment with cognitive restructuring. These results are
      disappointing in light of all that has been written about the likely benefits of
      combining cognitive and behavioral therapy in the treatment of social phobia. For
      example, it has been hypothesized that fear of negative evaluation is a key
      factor in social phobia and that change in this construct should be the goal of
      treatment. There is some research that supports this claim and other evidence
      that suggests that exposure alone is not particularly effective in producing
      those changes. Butler concluded that the treatment of social phobia is made more
      difficult whe

PMID- 8748384
TI  - Generalized anxiety disorder. Longitudinal course and pharmacologic treatment.
AB  - GAD generally is a fairly prevalent disorder occurring at a rate (even in its
      "pure" form) that equals or exceeds the other anxiety disorders such as panic
      disorder and social phobia. GAD tends to have an early age of onset and tends to
      exhibit a high degree of chronicity that frequently is complicated by comorbidity
      with other anxiety disorders as well as by depression and other Axis I and II
      disorders. The pharmacologic treatment of GAD should be conceptualized from the
      first day of treatment in terms of the long-term nature of the illness, in much
      the same way that treatment of affective disorders is now conceptualized. And yet
      an enormous amount of research remains to be done, as we know very little from
      controlled studies about how to optimize maintenance treatment of this relatively
      neglected disorder.

PMID- 8748385
TI  - Cognitive-behavior therapy for generalized anxiety disorder.
AB  - Overall, cognitive-behavior therapy shows promise as a treatment for GAD. The
      modest treatment gains reported to date may be in part due to the characterologic
      nature of GAD and the high rate of comorbidity. An important trend emerging in
      studies that provide long-term outcome data, however, is the substantial
      reduction in the use of anxiolytic medication in treated subjects. As a result,
      Brown et al have suggested that such cognitive-behavior therapy may offer an
      approach for discontinuing these medications in patients with GAD. Because the
      benefits of cognitive-behavioral treatment appear to be maintained at long-term
      follow-up assessment, cognitive-behavior therapy may provide a long-term and cost
      effective solution to GAD. The maintenance of treatment gains following a
      relatively short period of intervention (5-20 sessions) is particularly
      impressive given that the GAD population is characterized by individuals who say
      that they have "always been worriers" and who previously have been very difficult
      to treat. Future research is required to explore the specific effects that
      "nonspecific" methods offer. In addition, because some studies (e.g., Barlow et
      al) reported that dropouts in treatment were high and that many patients were
      left with some residual anxiety, there is clearly still a need for further
      research to find more focused and successful treatments.

PMID- 8748386
TI  - Anxiety in the elderly. Course and treatment.
AB  - Despite increasing research interest in the area of anxiety in younger age
      groups, few systematic studies of the course and treatment of anxiety disorders
      in the elderly have been performed. Data from Epidemiologic Catchment Area (ECA)
      studies suggest that anxiety disorders remain among the most prevalent of all
      psychiatric disorders in this age group. There is little information available
      about the late onset of anxiety disorders except for some evidence regarding
      panic disorder that suggests a distinct subtype with late onset and differences
      in vulnerability factors and phenomenology. Any evaluation of anxiety in the
      elderly should take into account multiple medical illnesses and medications that
      can produce a similar symptom picture. Thus, the importance of good history
      taking, empathy to the patient's psychosocial situation, and awareness of the
      possibility of an underlying medical condition cannot be overemphasized. A
      variety of compounds including benzodiazepines, buspirone, antidepressants, and
      beta blockers seems to show effectiveness for various anxiety disorders of the
      elderly. One needs to be cognizant of the great individual variation among the
      elderly and should be ready and willing to tailor usage of medications or
      cognitive-behavioral techniques to the patient's special needs. Proper education
      of the patient, leading to better compliance with the treatment regimen, and
      recent advances in treatment will almost certainly improve the outlook for these
      patients in the future for better functioning and a more optimistic prognosis.

PMID- 8748387
TI  - Psychotherapeutic issues in long-term treatment of anxiety disorder patients.
AB  - Although there have been impressive advances in the treatment of anxiety
      disorders during the past few decades, these have focused almost exclusively on
      short-term relief of anxiety symptoms. During this period, accumulated data have
      suggested that short-term, symptom-focused treatment is not sufficient for many
      patients. It is likely that ancillary psychotherapy treatment will be needed to
      enhance the extent and durability of response, reduce vulnerability to life
      stress, and bolster feelings of self-efficacy and controllability. These
      treatments will draw on strategies and techniques from traditional psychotherapy,
      but will need to incorporate more focused goals and regular assessments.

PMID- 8748388
TI  - Future directions in anxiolytic pharmacotherapy.
AB  - It seems that psychopharmacology may be well on its way toward the goal of
      developing new anxiolytic drug(s) that are fast acting and free from the unwanted
      effects associated with the traditional benzodiazepines. Several specific
      candidates exist, based upon rational targeting of neurotransmitter receptors
      shown to be linked to the neurobiology of anxiety. Thus, partial agonists at the
      benzodiazepine receptor, such as alpidem, abecarnil, and bretazenil, have highly
      promising preclinical profiles, and some useful preliminary results in clinical
      testing of anxiety disorder subjects. Neurosteroids are another interesting set
      of pharmacologic agents that target the benzodiazepine receptor, have a
      preclinical anxiolytic profile, and now need to be tested in clinical
      populations. Targeting of various serotonin (5HT) receptor subtypes is a very
      active area of current research for novel anxiolytic agents. 5HT3 antagonists may
      have an anxiolytic profile, but clinical results are still preliminary and need
      more validation. Of considerable interest is the idea of developing new drugs
      that act at 5HT1A, 5HT2A, or 5HT2C receptors. It has even been proposed that
      simultaneous targeting of both 5HT2A and 5HT1A receptors could result in robust
      anxiolytic agents that will have more immediate onset of action than currently
      available 5HT1A receptor acting drugs. Neuropeptide receptor agonists and
      antagonists with anxiolytic properties may represent one of the most striking new
      classes of potential anxiolytic drugs, but this is an emerging field that still
      requires considerably more systematic clinical testing. Nevertheless, preclinical
      studies as well as early clinical studies suggest that at least three
      neuropeptide receptors are provocative targets for novel anxiolytic agents:
      namely antagonists for CCK-B receptors, antagonists for CRF receptors, and
      agonists for neuropeptide Y receptors. Rational development of new pharmacologic
      agents based upon targeting receptors for those neurotransmitters that regulate
      the neurobiology of anxiety promises to bring forth a number of exciting
      therapeutic agents for the treatment of anxiety disorders in the future.

PMID- 8748389
TI  - Chromosomal mapping of the psychomotor stimulant effects of cocaine in BXD
      recombinant inbred mice.
AB  - To elucidate genes associated with cocaine's locomotor stimulant effects, we used
      recombinant inbred-quantitative trait loci (RI-QTL) analyses to identify
      chromosomal loci associated with locomotor activity before (baseline) and after
      cocaine treatment. RI-QTL analyses seek to identify associations between a
      quantitative measure of a phenotype and one or more previously mapped marker loci
      across a panel of RI strains. In the present study, 11 BXD RI strains were used
      to identify several putative QTLs for each phenotype. Both baseline locomotor
      activity and cocaine's locomotor stimulant effects are polygenic, with both
      unique and overlapping genetic influences. The largest associations for baseline
      activity were observed on chromosomes 5 and 9 and the largest associations for
      cocaine's psychomotor stimulant effects on chromosomes 3 and 17.

PMID- 8748390
TI  - High dose transdermal nicotine therapy for heavy smokers: safety, tolerability
      and measurement of nicotine and cotinine levels.
AB  - Transdermal nicotine has been shown to relieve nicotine withdrawal and to double
      smoking cessation rates compared to placebo in clinical trials. A 21 or 22 mg/day
      dose provides a steady state serum nicotine that is less than obtained from
      smoking. Limited information is available about higher nicotine patch doses. To
      define better the optimal dosing of nicotine patch therapy, we undertook an open
      label study to determine the safety and tolerability of 44 mg/day dose for
      smoking cessation in subjects smoking > or = 20 cigarettes per day. Forty smokers
      received 44 mg/day of transdermal nicotine for 4 weeks followed by 4 weeks of 22
      mg/day. Of the 40 subjects enrolled, 38 (95%) completed the 4 weeks of 44 mg
      patch therapy and 36 (90%) completed the entire 8 weeks of patch therapy. Non
      smokers at week 4 had a mean serum nicotine level of 23.4 +/- 11.7 ng/ml and
      cotinine of 152.2 +/- 87.3 ng/ml. Percent replacement was calculated by dividing
      the steady state level at week 4 by the baseline level while the subjects were
      smoking their usual number of cigarettes. Percent nicotine replacement for non
      smokers at week 4 (while on 44 mg nicotine patch) averaged 158% +/- 108.4, and
      for cotinine was 112.0 +/- 73.8. For nicotine, 33% of non-smokers at week 4 had <
      or = 100% nicotine replacement and for cotinine 63% < or = 100% replacement.
      Biochemically confirmed point prevalence smoking cessation rates were 65% and 55%
      at weeks 4 and 8 of patch therapy, respectively, and self-reported smoking
      cessation at 3 months was 50%. The most common effect was skin irritation at the
      patch site. A single subject was admitted for myocardial infarction following
      step-down from 44 to 22 mg of replacement nicotine. The subject was not smoking
      and the adverse event was deemed to be not related to the patch therapy. Sleep
      complaints were reported in 33% of subjects during the 44 mg phase. Other
      complaints were infrequent. We conclude that 44 mg per 24-h nicotine patch
      therapy in heavy smokers is safe, tolerable, and without significant adverse
      events.

PMID- 8748391
TI  - Influence of age, renal and liver impairment on the pharmacokinetics of
      risperidone in man.
AB  - The pharmacokinetics of the antipsychotic agent risperidone were investigated in
      healthy young and elderly subjects, cirrhotic patients and patients with moderate
      and severe renal insufficiency. In a comparative trial, a single oral 1-mg dose
      was administered to fasting subjects. Plasma and urine concentrations of the
      parent compound risperidone and the active moiety (i.e. risperidone plus 9
      hydroxy-risperidone) were measured by radioimmunoassays. No or only small changes
      in plasma protein binding were observed in hepatic and renal disease, whereas the
      protein binding was not influenced by aging. The inter-individual variability in
      plasma concentrations of the active moiety was much less than the variability in
      plasma concentrations of risperidone. Three out of six subjects, behaving like
      poor metabolizers, were on medication (thiethylperazine, amitriptyline,
      metoprolol) that may inhibit risperidone metabolism by CYP2D6 (debrisoquine 4
      hydroxylase). The pharmacokinetics of risperidone in elderly and cirrhotic
      patients were comparable to those in young subjects, whereas total oral clearance
      was reduced in renal disease patients. The elimination rate and clearance of 9
      hydroxy-risperidone was reduced in elderly and renal disease patients because of
      a diminished creatinine clearance. The CL(oral) of the active moiety, which is
      primarily 9-hydroxy-risperidone, was reduced by about 30% in the elderly and by
      about 50% in renal disease patients. In addition, the t1/2 of the active moiety
      was prolonged (19 h in young subjects versus about 25 h in elderly and renal
      disease patients). Based upon the pharmacokinetics of the active moiety, a dose
      reduction and a cautious dose titration is advised in the elderly and in patients
      with renal disease. In cirrhotic patients, the single-dose pharmacokinetics were
      comparable to those in healthy young subjects.

PMID- 8748392
TI  - Effects of several benzodiazepines, alone and in combination with flumazenil, in
      rhesus monkeys trained to discriminate pentobarbital from saline.
AB  - The purpose of the present study was to further investigate the relationship
      between the DS effects of PB and those of benzodiazepines (BZs) and to begin to
      collect pharmacological information concerning receptor mechanisms involved in
      this behavioral effect of BZs. Rhesus monkeys (n = 3), trained to discriminate
      pentobarbital (PB; 10 mg/kg, IG) from saline under a discrete-trials shock
      avoidance procedure, were given IG diazepam (0.3-10 mg/kg), chlordiazepoxide (1.0
      30 mg/kg), or etizolam (0.3-10 mg/kg) alone and in combination with flumazenil
      (0.01-1.7 mg/kg, IM). Flumazenil was administered 10 min prior to the
      administration of saline, PB or the BZs. All three BZs fully substituted for PB
      in all monkeys. Diazepam was the most potent with a mean ED50 of 0.81 mg/kg (SEM
      = 0.04) while chlordiazepoxide was the least potent (mean ED50 = 5.78 mg/kg, SEM
      = 1.22 mg/kg). The ED50 for etizolam was 1.22 mg/kg (SEM = 0.37 mg/kg).
      Pretreatment with flumazenil (0.01-1.0 mg/kg) resulted in a dose-related parallel
      shift to the right in the dose-response function for PB-appropriate responding in
      all monkeys for all three BZs. The mean (n = 3) pKB value with 0.1 mg/kg
      flumazenil was 6.51 (SEM = 0.42) for diazepam and 6.57 (SEM = 0.17) for
      chlordiazepoxide. This value could not be calculated for etizolam because only
      one monkey was tested with 0.1 mg/kg flumazenil. However, the mean pKB for
      etizolam considering all monkeys and all doses of flumazenil was 6.58 (SEM =
      0.47). Apparent pA2 values for flumazenil with diazepam were 6.02 for one monkey
      and 7.11 for another. All three BZs tended to increase average latency to
      respond. Apparent pKB and pA2 analysis may prove useful for elucidating receptor
      mechanisms involved in the behavioral effects of BZs.

PMID- 8748393
TI  - 5-HT2C receptor-mediated phosphoinositide turnover and the stimulus effects of m
      chlorophenylpiperazine.
AB  - The present study was designed to investigate the hypothesis that agonist
      interactions at 5-HT2C receptors mediate the discriminative stimulus properties
      of m-chlorophenylpiperazine (mCPP). Three structural classes of compounds have
      been described to stimulate increases in phosphoinositide (PI) hydrolysis at the
      5-HT2C receptor site: phenylpiperazines, phenylalkylamines, and indolamines. Four
      representative phenylpiperazines, mCPP, TFMPP, MK-212 and quipazine, one
      phenylalkylamine, (-)DOM, and one indolamine, LSD, were employed in the present
      study. The efficacies of these compounds were defined (1) in vitro, with respect
      to their abilities to stimulate increases in PI hydrolysis in the choroid plexus,
      and (2) in vivo with respect to their abilities to substitute for the mCPP
      discriminative stimulus. In vitro intrinsic activity at the 5-HT2C site was
      expressed as a fraction of the maximal PI hydrolysis response elicited by
      serotonin (5-HT). MK-212 (fractional efficacy = 1.1) and (-)DOM (0.77) were full
      agonists, while mCPP (0.72), LSD (0.27), quipazine (0.24), and TFMPP (0.22) were
      partial agonists with respect to the stimulation of PI hydrolysis at the 5-HT2C
      receptor. In vivo, each of the phenylpiperazines fully substituted for the mCPP
      stimulus, while (-)DOM (75%), and LSD (67%) elicited only partial substitution.
      While compounds with agonist activity at the 5-HT2C receptor in vitro substitute
      for the mCPP stimulus in vivo, no clear relationship exists between in vitro
      intrinsic activity at the 5-HT2C receptor with respect to the stimulation of PI
      turnover and maximal substitution for the mCPP stimulus in vivo. The present data
      suggest that mCPP elicits a compound stimulus which is mediated by agonist
      interactions at the 5-HT2C receptor and possibly additional interactions with 5
      HT2A, 5-HT3, and/or 5-HT1B receptors.

PMID- 8748395
TI  - Component structure of the expanded Brief Psychiatric Rating Scale (BPRS-E).
AB  - The component structure of the expanded Brief Psychiatric Rating Scale (BPRS-E)
      was analyzed in a sample (n = 150) of consecutively admitted general psychiatric
      inpatients and compared with a group (n = 97) of adolescent patients with
      schizophrenia spectrum diagnoses. A stable five-component solution, of which four
      were interpretable, was found across groups. The component scales of the 24-item
      version of the BPRS had good internal consistency, allowed better coverage of
      schizophrenia and affective symptoms than the 18-item version but did not
      distinguish the schizophrenia diagnostic subgroups. The implications of the
      findings are discussed.

PMID- 8748394
TI  - Effects of oxazepam on event-related brain potentials, EEG frequency bands, and
      vigilance performance.
AB  - Eighteen males performed two vigilance tasks with static and dynamic stimuli
      under the influence of oxazepam (20 and 40 mg) in a placebo-controlled, double
      blind, crossover design. Oxazepam dose-dependently impaired overall level of
      performance and aggravated the decrement with time in measures of accuracy and
      sensitivity relative to placebo. The drug reduced the amplitudes of the P1, N1,
      P2N2, and P3 (dose-dependently) waves of event-related potentials (ERPs).
      Oxazepam aggravated the linear decline with time of the P3 amplitude only.
      Oxazepam impaired accuracy was related to deterioration of central processing
      involved in stimulus discrimination (P2N2). Impairment of response-related
      performance measures (RT and RI) was associated with processing manifest in the
      P1, N1, and P3 waves. Oxazepam effects on the amplitudes of N1 and P3 correlated
      with drug effects on power in alpha 1 (8-10 Hz). Drug effects on overall
      performance and alpha were also related; the drug effect on response speed
      correlated only with the drug effect on beta 1 (12.5-21 Hz). Effects of time-on
      task on performance and EEG were unrelated, but oxazepam induced performance
      declines with time may have been caused by declines in resource allocation, as
      manifest in the amplitude of P3. Time effects on EEG power bands and ERP
      amplitudes were not significantly related to the time course of oxazepam
      activity. A curious dissociation emerged: both oxazepam and time-on-task impaired
      performance, but the drug induced a decrease of theta and alpha 1 power, whereas
      time-on-task increased power. Various processes play a role in performance
      decrements with time, and various aspects of processing may be involved in signal
      detection measures which makes terms such as sensitivity quite meaningless. So
      called computational processing was indistinguishable from energetic processes,
      which questions the validity of the distinction between these two domains.
      Explanations of EEG activity in terms of a unidimensional theory of arousal are
      untenable.

PMID- 8748397
TI  - Genetic differences in intravenous cocaine self-administration between C57BL/6J
      and DBA/2J mice.
AB  - In experiment 1, two different strains of mice [C57BL/6J (B6) and DBA/2J (D2)]
      were allowed to nosepoke for 5 microliters intravenous (IV) infusions during 2-h
      daily sessions. Two nosepoke holes were available, only one of which was
      reinforced on an FR-3 schedule with a 10-s time-out indicated by a light inside
      the reinforced nosepoke hole. During the first nine sessions, infusions were
      saline. On subsequent sessions, mice acquired nosepoking for 0.5 mg/kg cocaine.
      Finally, all mice were extinguished by again receiving only saline infusions.
      Cocaine acted as a reinforcer in both strains. In experiment 2, different mice
      from the same two strains were allowed to acquire nosepoking for IV cocaine at
      one of three unit doses (0.5, 1.0, or 2.0 mg/kg). Although there were no effects
      of unit dose on rate of acquisition, B6 mice were faster in acquiring self
      administration behavior than were D2 mice. Experiment 3 assessed behavior in the
      same mice, after acquisition had occurred. D2 mice nosepoked at a lower rate at
      asymptote than did B6 mice, but with a higher preference for the cocaine
      reinforced hole. Unit doses of cocaine were then manipulated within subjects,
      from 0.125 to 2.0 mg/kg per infusion. Higher doses yielded lower response rates
      than lower doses, both between and within subjects. Behavior in D2 mice relative
      to B6 mice also appeared to be shifted to the left of the dose-response curve
      measured within-subjects. Together, these findings indicate that although cocaine
      serves as a reinforcer in both strains, there are genetic differences in the
      pattern of cocaine self-administration between these two mouse strains.

PMID- 8748396
TI  - Dissociation between cognitive and motor/motivational deficits in the delayed
      matching to position test: effects of scopolamine, 8-OH-DPAT and EAA antagonists.
AB  - The effects of the muscarinic antagonists scopolamine HBr and MeBr, the 5-HT1A
      agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and the N-methyl-d
      aspartate (NMDA) antagonists MK-801 and CGS-19755 on performance of rats in a
      delayed matching-to-position task were examined. Pretreatment with scopolamine
      HBr (0.05 and 0.1 mg/kg), resulted in a delay-dependent decrease in the
      percentage of correct responses and discriminability (log d), but had no effect
      on either the latency to complete trials, or the rate of trial completion during
      the fixed duration session. Scopolamine MeBr (0.1 mg/kg) did not impair percent
      correct or increase the response latency but did decrease the rate of trial
      completion. 8-OH-DPAT (up to 0.3 mg/kg), had no effect on percent correct, but
      did induce a small decrease in discriminability. The impairment in
      discriminability occurred only at a dose that substantially reduced the rate of
      trial completion. Both MK-801 (0.05 mg/kg) and CGS 19755 (10 mg/kg) induced a
      delay-independent impairment in percent correct, discriminability and a reduction
      in the rate of trial completion without affecting latency. A lower dose of CGS
      19755 (5.0 mg/kg) induced a slight impairment in discriminability without
      significantly affecting the other measures. Taken together, these results
      demonstrate some dissociation between drug-induced cognitive and
      motor/motivational deficits in the DMTP test. However, the data question the
      specificity of putative cognitive impairments reported in many previous studies
      with the 5-HT1A agonist 8-OH-DPAT.

PMID- 8748398
TI  - Effects of adenosine agents on apomorphine-induced yawning in rats.
AB  - In the present work, adenosine agonists and antagonists on apomorphine-induced
      yawning in rats was investigated. Subcutaneous (SC) injection of apomorphine
      (0.02, 0.05 and 0.1 mg/kg) induced dose-dependent yawning behaviour in rats.
      Intracerebroventricular (ICV) administration of different doses of the drug (1,
      3, 5 micrograms/rat) also caused a dose-related yawning. ICV administration of
      the adenosine receptor agonists 5-N-ethylcarboxamidoadenosine (NECA) and N6
      cyclohexyladenosine (CHA) decreased apomorphine-induced yawning. The response
      induced by the adenosine agonists was reduced by 8-phenyladenosine (8-PT)
      pretreatment. The yawning induced by SC and ICV administration of apomorphine was
      decreased by ICV or IP injection of theophylline, respectively. It is concluded
      that at least A1 adenosine receptors may exert negative influence on the
      apomorphine-induced yawning. However, the exact mechanism(s) of adenosine
      receptors in this behaviour remain to be established.

PMID- 8748399
TI  - Effects of GABAergic drugs on physostigmine-induced yawning in rats.
AB  - In the present work the effects of GABA agonists and antagonists on yawning
      induced by physostigmine have been studied. Intraperitoneally (IP) injection of
      physostigmine (0.05-0.3 mg/kg) induced dose-related yawning in rats. The maximum
      yawning response was observed with 0.2 mg/kg of the drug. The GABA agonists
      muscimol (1-4 mg/kg) and baclofen (0.125-1 mg/kg) decreased yawning induced by
      physostigmine (0.2 mg/kg) dose dependently. Combination of both GABA agonists
      elicited greater inhibition of yawning. The GABA-A antagonists bicuculline or
      picrotoxin but not the GABA-B antagonist phaclofen reduced the inhibitory
      response induced by muscimol, whereas phaclofen but not bicuculline or picrotoxin
      reduced baclofen's inhibitory effect. Administration of bicuculline, picrotoxin
      or phaclofen also decreased the yawning induced by physostigmine. However, when
      the GABA-A and GABA-B antagonists were employed in combination, the inhibitory
      responses of both drugs were lost. It is concluded that GABA-A and/or GABA-B
      receptor stimulation may inhibit physostigmine-induced yawning.

PMID- 8748400
TI  - Different methods of assessing nicotine-induced antinociception may engage
      different neural mechanisms.
AB  - Two methods were used to assess nicotine-induced antinociception: tail withdrawal
      from a hot water bath and hind paw withdrawal from a hotplate. Nicotine doses
      which produced 75-80% maximum response were 0.75 mg/kg (free base) for tail
      withdrawal and 0.35 mg/kg for paw withdrawal. The peripheral blocker
      chlorisondamine (0.1 mg/kg, SC) and the central antagonist, mecamylamine (1
      mg/kg, SC) were each effective in blocking nicotine-induced increases in tail
      withdrawal latencies, suggesting that this effect of nicotine depends on either
      the action of nicotine at peripheral receptors or the functional integrity of
      those receptors. In contrast, nicotine-induced increases in paw withdrawal
      latencies were blocked by mecamylamine but not by chlorisondamine, even at other
      agonist/antagonist dose combinations. The results indicate that these two effects
      of nicotine involve at least partially separate pathways and may reflect a
      different mix of the antinociceptive and motor depressing effects of nicotine.

PMID- 8748401
TI  - Effects of high doses of theophylline on memory acquisition.
AB  - Intraperitoneal (IP) injection of high doses of theophylline decreased memory
      acquisition dose dependently. Low but not high doses of the dopamine receptor D2
      antagonist sulpiride and the dopamine D1 receptor antagonist SCH 23390 decreased
      the theophylline response. Pimozide and the beta-adrenoreceptor propranolol also
      decreased the drug response. The anti-muscarinic agent atropine, the alpha
      adrenoceptor phenoxybenzamine and the 5-HT antagonist metergoline did not affect
      the response induced by theophylline. It is concluded that dopamine and beta
      adrenergic receptor mechanisms may be involved in the theophylline-induced
      attenuation of memory acquisition.

PMID- 8748402
TI  - Role of drug-administration cues in the associative control of morphine tolerance
      in the rat.
AB  - This research investigated the role of injection procedures as a potential
      confound in the study of associative and nonassociative morphine tolerance
      development. Rats administered a series of morphine injections paired with a
      distinctive context environment can develop tolerance controlled associatively by
      the context. However, rats given morphine unpaired with the context may also
      develop some degree of tolerance. This study examined whether this tolerance
      represents an associative effect with animals using the injection ritual as a cue
      predictive of morphine delivery. Following 14 days of habituation to handling and
      injection stimuli, rats were given eight morphine injections (20 mg/kg, IP)
      explicitly paired or unpaired with a distinctive context. Animals were then
      tested for morphine analgesia in the context after either a 30-day rest condition
      or a 30-day period of daily saline injections. Analgesia was assessed by the tail
      flick method, and tolerance was defined as the shift to the right of the dose
      response curve of morphine-experienced relative to saline control animals. Paired
      animals across both retention conditions displayed tolerance, whereas tolerance
      retention in unpaired animals was observed only in those animals not given saline
      injections over the 30-day interval. Results support an associative
      interpretation of tolerance observed in unpaired conditions and suggest that the
      injection ritual may provide highly salient cues for the support of associative
      tolerance effects.

PMID- 8748403
TI  - Urinary excretion of albumin and transferrin in lithium maintenance treatment:
      daily versus alternate-day lithium dosing schedule.
AB  - Urinary excretion of albumin and transferrin was determined by means of sensitive
      immunochemical methods in 40 manic-depressive patients prior to and following 6
      months of daily or alternate-day lithium carbonate treatment. The median dose of
      lithium carbonate was 700 mg in the daily treatment group and 1200 mg in the
      alternate-day group, the corresponding median 12-h serum lithium concentration
      being 0.6 mmol l-1 and 0.7 mmol l-1, respectively. Urinary excretion of albumin
      and transferrin was significantly elevated in the lithium-treated patients as
      compared to a control group (Mann-Whitney). The change in urinary
      albumin:creatinine and transferrin:creatinine ratios between allocation and 6
      months of treatment did not correlate significantly with the lithium dosing
      schedule (multiple linear regression), but did correlate with total lithium
      carbonate dose. In conclusion, the study provides no evidence of any difference
      in glomerular function (permeability) in the daily and alternate-day lithium
      dosing schedules, and lends no support to the hypothesis that alternate-day
      treatment diminishes the effect of lithium on renal function.

PMID- 8748404
TI  - Allograft survival following immunization with membrane-bound or soluble peptide
      MHC class I donor antigens: factors relevant for the induction of rejection by
      indirect recognition.
AB  - T cells recognize foreign antigens in the form of peptide fragments resulting
      from antigen processing by antigen-presenting cells. In contrast to this indirect
      recognition, MHC molecules of foreign cells can be directly recognized by T
      cells. Direct recognition has for a long time been considered the only mechanism
      responsible for transplant rejection. Recent studies have provided evidence of a
      role of indirect recognition in rejection. In the current series of experiments,
      we studied the influence of indirect alloactivation, induced either by donor MHC
      class I peptides or by membrane-bound MHC I molecules, on heart allograft
      rejection in rats. Recipients were immunized before transplantation with
      synthetic donor MHC I peptides. The animals developed antibody and T-cell
      responses. Depending on the rat strain, peptide pretreatment either had no effect
      on graft survival (DA-->PVG; untreated controls 8.5 +/- 0.6 days, treated rats
      9.5 +/- 0.6 days) or led to accelerated rejection (DA-->LEW; untreated controls
      7.5 +/- 0.3 days, treated rats 5.1 +/- 0.2 days; P < 0.0002). Importantly,
      sensitization by indirect activation induced acute rejection in a donor-recipient
      combination (LEW.1A-->LEW.1WR2) in which neither direct nor indirect recognition
      led to rejection (untreated controls > 400 days, pretreated rats 15 +/- 4.2
      days). Another group of animals was immunized with allogeneic or congenic
      erythrocytes carrying the MHC I antigen from which the peptides were derived.
      Although the immunization elicited a measurable immune response, it did not lead
      to accelerated rejection. We conclude that sensitization by indirect recognition
      is able to initiate an acute rejection even in recipients in which neither direct
      nor indirect recognition is effective, and that this effect is strain-dependent.
      The form in which the donor antigen is administered is decisive for the induction
      of rejection by indirect activation.

PMID- 8748405
TI  - Supersensitivity mismatch of adenosine in the transplanted human heart: chrono-
      and dromotropy versus inotropy.
AB  - Supersensitive negative chronotropic and dromotropic effects have been described
      for adenosine after human heart transplantation. The present study investigated a
      potential antiadrenergic negative inotropic effect of adenosine in heart
      transplant recipients compared to normal subjects. Sinus cycle length, PR
      interval, blood pressure, and inotropic response in vivo were compared in seven
      orthotopic heart transplant recipients and seven healthy volunteers (controls).
      Fractional shortening, velocity of circumferential fiber shortening, and systolic
      pressure/dimension ratio were calculated using M-mode echocardiography. Baseline
      ventricular contractility was normal in both groups. Although adenosine induced a
      significant exaggeration of the negative chronotropic and dromotropic effect in
      the transplant group, the positive inotropic effect of 20 ng/kg x min
      isoproterenol (FS 53.2 +/- 8.8 vs 51.0 +/- 4.6%, P/D 5.8 +/- 1.9 vs 6.0 +/- 0.8
      mm Hg/mm, Vcf 0.21 +/- 0.04 vs 0.20 +/- 0.02%/ms for heart recipients vs
      controls) was not reduced by the additional administration of 150 micrograms/kg
      adenosine (FS 52.2 +/- 8.6 vs 51.7 +/- 5.6%, P/D 5.5 +/- 1.5 vs 5.4 +/- 0.8 mm
      Hg/mm, Vcf 0.24 +/- 0.07 vs 0.21 +/- 0.02%/ms for transplant recipients vs
      controls). In contrast to a chronotropic and dromotropic supersensitivity,
      adenosine does not attenuate the catecholamine-induced increase in contractility
      in the human ventricle in vivo after heart transplantation.

PMID- 8748406
TI  - Graft size-matching in living related partial liver transplantation in relation
      to tissue oxygenation and metabolic capacity.
AB  - The influence of graft size-matching on tissue oxygenation and metabolic
      capability was studied in living related partial liver transplantations for 47
      pediatric patients. Their age ranged from 4 months to 17 years 3 months, their
      body weight from 4.0 to 58.0 kg, graft weight from 191 to 440 g, and graft
      weight/recipient body weight ratio from 0.61% to 6.0%. Tissue oxygenation and its
      heterogeneity were investigated by measuring oxygen saturation of hemoglobin in
      the liver sinusoid (SO2), coefficient of variation of SO2, and arterial ketone
      body ratio. The metabolic capacity of the graft was investigated by measuring
      bilirubin clearance, recovery of cholesterol esterification, and ketone body
      production. In infants with a relatively large liver graft, both intra- and
      extracellular oxygenation remained low soon after reperfusion but recovered to
      the control value by the end of the operation. In adolescent recipients of a
      relatively small graft, by contrast, synthetic and detoxification capacities were
      relatively deficient; however, these improved with time. These results indicate
      that sufficient tissue oxygenation and liver regeneration are essential for
      successful liver transplantation with relatively large and small grafts,
      respectively.

PMID- 8748407
TI  - Conversion to tacrolimus after liver transplantation.
AB  - We have reviewed our experience with conversion to tacrolimus after 435 liver
      transplantations. Tacrolimus was administered as a rescue agent in 33 patients
      until October 1993. Indications for rescue therapy were: cholestatic forms of
      severe, steroid-resistant cellular rejection (n = 8), OKT3-resistant cellular
      rejections (n = 6), cellular rejections in patients suffering from cyclosporin
      malabsorption (n = 4), late onset cellular rejections (n = 4), early chronic
      rejections (n = 3), and chronic vascular or ductopenic rejections (n = 8).
      Response was evident in 29 of the 33 patients (88%), whereas 4 patients (12%)
      were nonresponsive. Patient and graft survival were 76% and 70%, respectively.
      Graft loss with or without patient death occurred in three of eight patients
      suffering from severe, steroid-resistant cellular rejection, in two of six
      patients with OKT3-resistant cellular rejections, and in five of eight patients
      undergoing chronic rejection. In severe steroid-resistant cellular rejection,
      successful tacrolimus rescue therapy corresponded to a significantly lower total
      serum bilirubin than unsuccessful therapy (12.0 +/- 5.6 mg% vs 29.7 +/- 5.9 mg%,
      P < 0.05). We conclude that tacrolimus rescue therapy is a safe and efficient
      alternative for high-risk cases that do not respond to conservative treatment. In
      severe, steroid-resistant cellular rejection and in chronic ductopenic rejection,
      conversion to tacrolimus is beneficial only in a limited number of cases. A
      predictive parameter, which total serum bilirubin may prove to be in severe,
      steroid-resistant cellular rejection, is needed to select those cases that might
      benefit more from retransplantation than from conversion to tacrolimus.

PMID- 8748408
TI  - A novel dextran 40-based preservation solution.
AB  - Although the University of Wisconsin (UW) solution has become the standard
      solution for the preservation of kidneys for transplantation, the importance of
      the colloid hydroxyethylstarch (HES), one of the key compounds of the UW
      solution, has been questioned repeatedly. It is now established that HES is not
      necessary for routine kidney preservation. However, colloids may still be
      advantageous in UW like solutions for the purpose of multiorgan procurements and
      the preservation of organs from marginal donors. It has been shown in various
      experimental models that dextran 40 may successfully substitute for HES. Dextran
      40 is not only cheaper but also has a variety of biological effects that may be
      beneficial during the graft reperfusion phase. The aim of this clinical study was
      to examine the efficacy of a dextran 40-based preservation solution (Dex-PS) for
      its use in human kidney graft preservation and to compare the transplantation
      results with kidneys preserved with UW solution. A total of 87 kidneys were
      preserved with Dex-PS and matched with 87 kidneys preserved with UW solution.
      Both groups were comparable in terms of donor and recipient characteristics and
      both had a high proportion of kidneys from nonheart-beating donors. Patient
      survival and graft survival after 1 year were 95% and 86% for the Dex-PS group
      and 94% and 90% for the UW group, respectively (P = NS). Primary nonfunction,
      delayed graft function, postoperative need for dialysis, and follow-up of serum
      creatinine were statistically comparable between these two groups. We conclude
      that dextran 40 can safely replace HES in UW solution for the purpose of clinical
      kidney preservation. There were no statistically detectable differences in graft
      performance between the kidneys preserved with UW and those preserved with Dex
      PS.

PMID- 8748409
TI  - Heart transplant candidates at high risk can be identified at the time of initial
      evaluation.
AB  - The increasing discrepancy between the numbers of patients selected for cardiac
      transplantation and the available donor organs requires validation of markers of
      high risk at the time of initial evaluation that may help to determine which
      patients profit from aggressive therapy. We retrospectively examined the case
      records of 91 heart transplant candidates selected out of a total of 140
      consecutive patients referred for evaluation. Of these 91 patients, 48 were
      transplanted during follow-up. Of the remaining 43 patients, 25 died after a mean
      survival time of 1.6 +/- 2.5 months. The causes of death were pump failure in 18
      (72%) and sudden cardiac death in 7 (28%). Multivariate analysis identified 4 out
      of 26 parameters at initial evaluation that distinguished the 25 nonsurvivors
      from the 18 survivors. These were: mean arterial pressure (P = 0.03), pulmonary
      capillary wedge pressure (P = 0.002), mean pulmonary artery pressure (P = 0.001),
      and fractional shortening (P = 0.007). The mode of death could not be predicted.
      We conclude that there are prognostic markers at initial evaluation that allow
      more restrictive selection of patients for cardiac transplantation and mechanical
      bridging.

PMID- 8748410
TI  - Antibodies directed at mouse IL-2-R alpha and beta chains act in synergy to
      abolish T-cell proliferation in vitro and delayed type hypersensitivity reaction
      in vivo.
AB  - The anti-mouse IL-2-R beta chain mAb TM-beta 1 which, by itself, does not affect
      IL-2-dependent proliferation through the high affinity mouse IL-2 receptor, was
      shown to cooperate in a synergistic way with a set of anti-IL-2-R alpha chain
      mAbs both in vitro and in vivo. In vitro, when associated at equimolar
      concentrations, the TM-beta 1/anti-alpha mAb association was four to ten times
      more efficient at inhibiting the proliferation of the CTL-L2 cell line than was a
      similar concentration of anti-alpha mAb alone. In addition, a bispecific antibody
      in which a Fab' fragment of TM-beta 1 was covalently linked to a Fab' fragment of
      one of the anti-alpha mAb (5A2) was shown to be as efficient as the TM-beta 1/5A2
      association. The association of TM-beta 1 with 5A2 was also tested in vivo in a
      sheep red blood cell-induced delayed type hypersensitivity (DTH) model. TM-beta 1
      which, by itself, had no effect on DTH, induced a two- to threefold decrease in
      the doses of 5A2 required to suppress this cell-mediated immune reaction.

PMID- 8748411
TI  - A prospective randomised study of the effect of nicardipine on ischaemic renal
      injury in renal allografts.
AB  - In a prospective double-blind trial, 127 kidneys were randomised to receive
      Eurocollins (n = 65) or Eurocollins plus nicardipine (n = 62) as a second flush
      solution at the time of organ retrieval. Delayed graft function occurred in 18 of
      65 control kidneys (28%) and in 20 of 62 nicardipine kidneys (32%; P = 0.7,
      Fischer's exact test). The mean (SD) serum creatinine at 6 weeks was 197 (138)
      mumol/l in the Eurocollins group and 195 (159) mumol/l in the nicardipine group
      (P = 0.95). Eighteen recipients (28%) in the controlled Eurocollins group
      experienced a rejection episode in the first 6 weeks post-transplant compared to
      17 (27%) in the nicardipine group (chi 2 with Yates' correction = 0.027; P = >
      0.95). In this study, the addition of nicardipine to the kidney perfusion fluid
      did not have a beneficial effect on kidney function following transplantation.

PMID- 8748412
TI  - Impaired renal artery blood flow at transplantation is correlated to delayed
      onset of graft function.
AB  - The aim of this prospective study was to evaluate a transit time flowmeter
      (Transonic, USA) in renal transplantation with respect to feasibility and
      estimation of graft circulation. Subsequently, the measurements were evaluated
      for their ability to predict delayed onset of function, occurrence of acute
      rejection or graft loss within 3 months after transplantation. Renal artery blood
      flow was measured and resistance calculated in 100 transplants-62 cadaveric donor
      (CD) and 38 living donor (LD)-immediately after restoration of graft circulation
      and before wound closure. Low blood flow (< 250 ml/min) and high resistance (>
      392 mPRU) correlated positively with a long cold ischemia time and delayed onset
      of graft function, including the need for post-transplant dialysis. No
      correlation with rejection or graft loss was found. Blood flow measurements with
      the transit time flowmeter were easy to perform and immediate estimation of
      transplant circulation was achieved. Transplants at risk for delayed onset of
      function were identified.

PMID- 8748413
TI  - The impact of midline versus transverse incisions on wound complications and
      outcome in simultaneous pancreas-kidney transplants: a retrospective analysis.
AB  - Intraperitoneal placement of the pancreas allograft, usually through a midline
      incision, has so far achieved the best results in pancreas transplantation. The
      usefulness and safety of a transverse incision has not been previously reported.
      The purpose of this study was to compare midline and transverse incisions, with
      respect to wound complications and outcome, in simultaneous pancreas-kidney
      transplant recipients with intraperitoneal placement of the pancreatic graft. The
      incidence of deep abscess formation, superficial abscess formation, wound leak,
      and fascial dehiscence, as well as graft survival, were retrospectively compared
      in 41 bladder-drained simultaneous pancreas-kidney recipients with a midline
      incision and in 15 with a transverse incision. The overall incidence of wound
      complications was similar (34% vs 20%, P = NS) in the two groups. Deep abscess
      formation occurred more frequently in the midline group (27% vs 0%, P = 0.02).
      Staphylococcus epidermidis and Candida albicans were the most common microbial
      isolates from deep abscesses. Multivariate logistic regression analysis revealed
      donor age 40 years or older (P = 0.04), the occurrence of a bladder leak (P =
      0.05), and a peak serum amylase in the 1st week of 1000 IU/l or greater (P =
      0.02) to be independent risk factors for the development of wound complications.
      The type of incision, however, was not found to be an independent risk factor.
      Patient (90% vs 83%, P = NS), pancreas allograft (78% vs 82%, P = NS), and kidney
      allograft (83% vs 70%, P = NS) survival rates were similar for the midline and
      transverse groups. We conclude that the transverse incision is a reasonable
      alternative to the midline incision in simultaneous pancreas-kidney
      transplantation and it is presently the incision of choice at our institution. It
      offers excellent exposure and is associated with a similar wound complication
      rate and outcome when compared to the midline incision.

PMID- 8748414
TI  - Hemolytic uremic syndrome in solid-organ transplant recipients.
AB  - Post-transplant hemolytic uremic syndrome characterized by microangiopathic
      hemolysis, thrombocytopenia, and renal failure is an infrequent but potentially
      serious complication in organ transplant recipients. Hemolytic uremic syndrome
      developed in 2% (2/100) of our consecutive liver transplants. We report our
      patients and review a total of 91 cases of hemolytic uremic syndrome in adult
      solid organ transplant recipients reported in the literature. Ninety percent were
      observed in renal transplant recipients, 8% in liver, and 1% each in lung and
      heart transplant recipients. Eighty percent and 96% of cases occurred within 90
      days and 1 year, respectively, post-transplantation. In renal transplant
      recipients, 23% of cases were due to post-transplant recurrence of hemolytic
      uremic syndrome. In 50% of renal transplant recipients and in all nonrenal solid
      organ transplant recipients, hemolytic uremic syndrome was attributed to
      cyclosporin or tacrolimus therapy. Notably, infections were not a significant
      precipitating factor for post-transplant hemolytic uremic syndrome. Graft loss
      attributable to hemolytic uremic syndrome occurred in 43% of renal transplant
      recipients while renal transplantation and hemodialysis were required in the lung
      and heart transplant recipients due to hemolytic uremic syndrome induced renal
      failure. The overall mortality was 13% (12/91). Physicians caring for transplant
      recipients need to be aware of this potentially severe graft and life-threatening
      disorder since prompt recognition and removal of identifiable risk factors is
      critical in the management of post-transplant hemolytic uremic syndrome.

PMID- 8748415
TI  - Liberation of vasoactive substances and its prevention with thromboxane A2
      synthase inhibitor in pig liver transplantation.
AB  - There are multiple causes of liver graft nonfunction in the early post-transplant
      period. Since a severe microcirculatory disturbance based on ischemia-reperfusion
      liver injury is considered to be the main underlying pathophysiology, it is
      suspected that various vasoactive substances are liberated after reperfusion of
      the graft. In order to investigate this matter, we conducted an experimental
      study with pig liver allotransplantation. Two groups of animals received donor
      grafts with or without thromboxane synthase inhibitor (sodium ozagrel), 1.25 mg/
      kg body weight intravenously, given at the time of liver harvesting. All of the
      recipient animals in the treatment group (n = 10) survived longer than 7 days
      whereas three of ten animals in the control group died within 7 days. Serum
      lactate dehydrogenase (LDH) in the recipient serum at 1 h after reperfusion was
      significantly lower in the treatment group (915.1 +/- 167.3 U/l) than in the
      control group (1264.4 +/- 134.7 U/l). Serum thromboxane B2 (2261.7 +/- 1055.7
      pg/ml) and endothelin-1 (6.3 +/- 2.2 pg/ml) after reperfusion in the treatment
      group were significantly lower than those in the control group (4220.0 +/- 1711.0
      pg/ml and 11.2 +/- 3.1 pg/ml, respectively). Although serum angiotensin II after
      reperfusion tended to be lower in the treatment group than in the controls serum
      renin activity was less than 3 ng/ml in both groups of animals. There were no
      differences in the plasma endotoxin levels between the two groups. We conclude
      that the administration of sodium ozagrel to the donor animals provided better
      graft function in recipients than no such treatment. We speculate that the
      inhibition of thromboxane A2 production suppresses the liberation of other
      vasoconstrictive substances, preventing microcirculatory disturbance and,
      thereby, contributing to improved graft function after liver transplantation.

PMID- 8748416
TI  - Living related liver transplantation. Progress or regress?
AB  - The impetus for the development of living related liver programmes lies with
      donor shortage, which relates inversely to the success of generating cadaveric
      donors. A shrinking or non-existent cadaveric donor pool leads to an increased
      death rate among potential recipients awaiting transplantation. The living
      related liver programmes have by and large been successful, though it is accepted
      that there is potentially a significant risk to the donors. The technique of live
      donor liver transplantation is clearly here to stay, but the selection of
      suitable donors is between the family and the unit. Consequently, because of the
      lack of international guidelines, the programmes are open to abuse. Steps should
      be taken to establish either mechanisms of control or a worldwide register to
      combat this potential.

PMID- 8748417
TI  - Percutaneous transluminal angioplasty in a transplanted kidney with fibromuscular
      dysplasia.

PMID- 8748418
TI  - Victims of cyanide poisoning make suitable organ donors.

PMID- 8748419
TI  - Comparison of pulmonary responses of asthmatic and nonasthmatic subjects
      performing light exercise while exposed to a low level of ozone.
AB  - To determine if asthmatic subjects (ASTH, n = 17) experience greater O3-induced
      pulmonary decrements than nonasthmatic subjects (NONA, n = 13), both groups were
      exposed for 7.6 h to both clean air and 0.16 ppm O3. Exposures consisted of seven
      50-min periods of light exercise (VE = 14.2 and 15.3 l/min/m2 for ASTH and NONA,
      respectively), each followed by 10 min rest. A 35-min lunch period followed the
      third exercise. Following O3 exposure, decrements in forced expiratory volume in
      one second (FEV1) and FEV1 divided by forced vital capacity (FVC), corrected for
      air exposure, for ASTH (-19.4 +/- 3.1% and -6.2 +/- 2%, respectively) were
      significantly greater (p = 0.04 and 0.02) than for NONA (-9.8 +/- 1.9% and -1 +/-
      1%, respectively). There was no difference (p = 0.33) for decrements in FVC
      between ASTH (-11.8 +/- 1.9%) and NONA (-8.8 +/- 2.1%). Nine of 17 ASTH
      experienced wheezing with O3, while only one experienced wheezing with air (p =
      0.004); no NONA experienced wheezing. Six of 17 ASTH requested inhaled beta
      agonist bronchodilator prior to and/or during O3 exposure and experienced some
      temporary alleviation of decrements. At end exposure, however, ASTH who were
      medicated had greater O3-induced decrements than those who were not medicated.
      ASTH who had the larger O3-induced decrements had lower baseline FEV1/FVC and
      lower baseline %predicted FEV1. These data indicate that in ASTH, unlike NONA,
      some portion of O3-induced pulmonary decrements experienced was related to
      bronchoconstriction, and that O3-responsiveness for ASTH depended upon baseline
      airway status.

PMID- 8748420
TI  - Developmental toxicity of Orange B given to rats in drinking water.
AB  - Orange B, a pyrazolone dye used to color frankfurter and sausage casings, was
      given in distilled drinking water to pregnant Osborne-Mendel rats throughout
      gestation. Assessed on the basis of fluid consumption, the dose levels of 0,
      0.05, 0.1, 0.2, and 0.4% corresponded to daily Orange B consumption of 0, 67.5,
      129.6, 266.6, and 532.3 mg/kg body weight, respectively. On gestation day 20, the
      females were euthanized and cesarean sections were performed. Throughout
      gestation, the treated animals consumed less fluid than did the controls, but the
      decreases were not dose-related. Feed consumption and maternal weight gain were
      not affected. No dose-related changes were seen in maternal clinical findings,
      implantations, fetal viability, or fetal size (weight and length). No compound
      related effects were seen in sternebral development. Ossification of the
      interparietal bones was reduced at some dose levels, but the decreases were
      considered random because of absence of dose response. No dose-related effect was
      seen in the incidence of skeletal variations in fetuses or in the number of
      litters containing fetuses with skeletal variations. Skeletal development, as
      measured by the average number of ossified vertebrae, was similar in all groups.
      Soft-tissue development was not affected by dose levels of 0.05 to 0.2%. In
      animals treated with 0.4% Orange B, significant increases were seen in the
      incidence of hydroureters (severe and moderate), in the average numbers of
      fetuses with at least one and at least two soft-tissue variations per litter, and
      in the percentage of litters containing fetuses with at least two soft-tissue
      variations.

PMID- 8748421
TI  - Application of beryllium antibodies in risk assessment and health surveillance:
      two case studies.
AB  - This paper demonstrates that current standards used by the Occupational Safety
      and Health Administration (OSHA) to establish an area free from potential
      beryllium contamination may be inadequate. Using the Beryllium Antibody Assay, it
      was shown that workers exposed to former beryllium work areas, thought to be
      sanitized and to meet OSHA standards, experienced statistically significant rises
      in blood beryllium antibody titers. This finding raises the question of whether
      the equipment currently required to protect workers in beryllium-laden
      environments is sufficient. The project mission of
      decommissioning/decontaminating the former nuclear weapons plant at Rocky Flats
      Environmental Technology Site (RFETS), instituted in 1992, has necessitated
      development of new technology directed toward safe and responsible cleanup.
      Challenges have been posed not only by the need to dispose of radioactive and
      chemical waste, but also by the problem of cleaning up hazardous metals such as
      the element beryllium. Beryllium was used extensively in research and the
      manufacture of nuclear weapons components at Rocky Flats for over 40 years. Since
      inhalation of this element can induce chronic beryllium disease (Eisenbud and
      Lisson, 1983), an antibody assay was developed to screen workers for internal
      exposure to beryllium. Exposure is indicated by a titer of antibodies greater
      than two standard deviations above a normal population control (defined as the
      mean titer of pooled samples from 51 individuals with no known exposure to
      beryllium) and a p-value of < 0.05. This paper describes two new applications for
      the assay: risk assessment and health surveillance. Case study 1 involves a team
      of three workers who cleaned a beryllium plenum and whose beryllium antibody
      titers provided a quantitative assessment of their exposure. Case study 2
      describes the use of the antibody assay to determine the probable manner in which
      one worker was exposed to beryllium while performing his duties as an
      architectural engineer.

PMID- 8748422
TI  - A simple index for representing the discrepancy between simulations of
      physiological pharmacokinetic models and experimental data.
AB  - The objective of this study was to develop an index that would provide a
      quantitative measure of the degree of discrepancy between simulations of
      physiologically based pharmacokinetic (PBPK) models and experimental data. The
      approach we developed involves the calculation of the root mean square of the
      error (representing the difference between the individual simulated and
      experimental values for each sampling point in a time course curve), and dividing
      it by the root mean square of the experimental values. The resulting numerical
      values of discrepancy measures for several data sets (each corresponding to an
      end point) obtained in a single experimental study are then combined on the basis
      of a weighting proportional to the number of data points contained in each data
      set. Such consolidated discrepancy indices obtained from several experiments
      (e.g., exposure scenarios, doses, routes, species) are averaged to get an overall
      discrepancy index, referred to as the PBPK index. This empirical index reflects
      the overall, weighted average percent difference between the a priori PBPK model
      simulations and experimental data. The proposed methodology is illustrated using
      previously published experimental and simulated data on dichloromethane
      pharmacokinetics in humans. The application of this kind of a "quantitative"
      method should help remove the ambiguity in communicating the degree of
      concordance or discrepancy between PBPK model simulations and experimental data.

PMID- 8748423
TI  - The effects of JP-8 jet fuel on male Sprague-Dawley rats after a 90-day exposure
      by oral gavage.
AB  - The U.S. Air Force is converting from JP-4 jet fuel to the less volatile JP-8 jet
      fuel, which is similar to commercial Jet Fuel A. Our previous 90-day inhalation
      study with JP-8 vapor, using F-344 rats and C57BL/6 mice, resulted in no
      treatment-related adverse effects other than alpha 2-microglobulin nephropathy in
      male rats (Mattie et al., 1991). In the present study, male rats were dosed with
      neat JP-8 (0, 750, 1500, 3000 mg/kg) daily by gavage for 90 days in an effort to
      characterize the kidney lesion and assess further any additional adverse effects
      associated with prolonged oral exposure to this fuel. Results of this study
      revealed a significant dose-dependent decrease in body weights of rats exposed to
      JP-8. Male rat-specific alpha 2-microglobulin nephropathy was observed by
      histopathologic examination. A number of significant changes were also seen in
      blood and urine that were not dose-dependent. Additional treatment-related
      effects were a gastritis and a perianal dermatitis. Although there were no
      histopathological or weight changes in the livers of exposed rats, there was an
      increase in the liver enzymes AST and ALT. The elevated enzymes did not increase
      with increasing dose of JP-8.

PMID- 8748424
TI  - Reproductive toxicity screen of ammonium dinitramide administered in the drinking
      water of Sprague-Dawley rats.
AB  - The Department of Defense is currently considering replacing ammonium perchlorate
      with ammonium dinitramide (ADN), a class 1.1 explosive oxidizer to be used in
      solid rocket propellant mixtures and explosives. This study was intended to
      evaluate the potential of ADN to produce alterations in paternal fertility,
      maternal pregnancy and lactation, and growth and development of offspring. Male
      and female rats received drinking water containing 0.0, 0.2, 1.0, or 2.0 g
      ADN/liter throughout the study. Mating occurred following 14 days of treatment.
      All dams, one-half the males, and representative pups were maintained for a total
      of 90 days of treatment. No mortality occurred in parental animals during the
      study. Treatment with ADN resulted in no adverse effects on mating; 92-100% of
      the animals mated. No treatment-related effects were seen in parental animals
      clinically or histopathologically. Adverse treatment-related effects were noted
      in maternal and paternal fertility indices, gestational indices, and live birth
      indices in both the mid- and high-dose groups. Litter sizes in the mid- and high
      dose groups were significantly smaller than those of the low-dose and control
      groups. Mean pup weights showed no statistically significant differences between
      ADN-treated pups and controls. Gross and histopathological examination of the
      animals failed to identify the cause for the decrease in litter production in the
      mid- and high-dose dams. This study indicates that ADN is a reproductive
      toxicant. The no-observable-effect level (NOEL) is 29 mg/kg/day, the median dose
      of the low level female rats.

PMID- 8748425
TI  - Acute and subacute toxicity tests of madder root, natural colorant extracted from
      madder (Rubia tinctorum), in (C57BL/6 X C3H)F1 mice.
AB  - As part of the safety assessment of madder root (MR), a food colorant extracted
      from madder (Rubia tinctorum), toxicity tests were undertaken using (C57BL/6 x
      C3H)F1 mice of both sexes. An acute toxicity test was performed by 14-day
      administration of MR dissolved in distilled water by gavage at doses of 0, 500,
      2000, 3500, and 5000 mg/kg body weight to groups of each sex. One male mouse
      dosed at 5000 mg/kg body weight was dead before the end of the study, indicating
      that the maximum tolerated dose of MR was between 3500 and 5000 mg/kg body
      weight. A subacute toxicity test of MR was performed using 62 mice of each sex,
      mixing their diets with MR at concentrations of 0, 0.3, 0.6, 1.25, 2.5, and 5%
      for 90 days. All mice tolerated these doses of MR well. The body weight gains of
      either sex were not affected by the treatment. None of the mice treated with MR
      showed clinical signs of toxicity. Histopathological examinations showed
      retention cysts of the kidneys and epidermal vaginal cysts in a few of the
      treated or control mice. No hyperplastic, preneoplastic, and neoplastic lesions
      and no pathological findings of toxicity were found. These results suggest that
      dietary exposure of MR at these doses has no acute or subacute toxic effects on
      mice.

PMID- 8748426
TI  - Over-the-counter hypnotics and chronic insomnia in the elderly.

PMID- 8748427
TI  - The emerging role of cytochrome P450 3A in psychopharmacology.
AB  - Recent advances in molecular pharmacology have allowed the characterization of
      the specific isoforms that mediate the metabolism of various medications. This
      information can be integrated with older clinical observations to begin to
      develop specific mechanistic and predictive models of psychotropic drug
      interactions. The polymorphic cytochrome P450 2D6 has gained much attention,
      because competition for this isoform is responsible for serotonin reuptake
      inhibitor-induced increases in tricyclic antidepressant concentrations in plasma.
      However, the cytochrome P450 3A subfamily and the 3A3 and 3A4 isoforms (CYP3A3/4)
      in particular are becoming increasingly important in psychopharmacology as a
      result of their central involvement in the metabolism of a wide range of steroids
      and medications, including antidepressants, benzodiazepines, calcium channel
      blockers, and carbamazepine. The inhibition of CYP3A3/4 by medications such as
      certain newer antidepressants, calcium channel blockers, and antibiotics can
      increase the concentrations of CYP3A3/4 substrates, yielding toxicity. The
      induction of CYP3A3/4 by medications such as carbamazepine can decrease the
      concentrations of CYP3A3/4 substrates, yielding inefficiency. Thus, knowledge of
      the substrates, inhibitors, and inducers of CYP3A3/ and other cytochrome P450
      isoforms may help clinicians to anticipate and avoid pharmacokinetic drug
      interactions and improve rational prescribing practices.

PMID- 8748428
TI  - Coadministration of nefazodone and benzodiazepines: III. A pharmacokinetic
      interaction study with alprazolam.
AB  - This study was conducted to determine the potential for an interaction between
      nefazodone, a new antidepressant, and alprazolam after single- and multiple-dose
      administration in a randomized, double-blind, parallel-group, placebo-controlled
      study in 48 healthy male volunteers. A group of 12 subjects received either
      placebo twice daily, 1 mg of alprazolam twice daily, 200 mg of nefazodone twice
      daily, or the combination of 1 mg of alprazolam and 200 mg of nefazodone twice
      daily for 7 days. Serial blood samples were collected after dosing on day 1 and
      day 7 and before the morning dose on days 4, 5, and 6 for the determination of
      alprazolam and its metabolites alpha-hydroxyalprazolam (AOH) and 4
      hydroxyalprazolam (4OH) and nefazodone and its metabolites hydroxynefazodone (HO
      nefazodone), m-chlorophenylpiperazine (mCPP), and a triazole dione metabolite
      (dione) by validated high-performance liquid chromatography methods. Steady-state
      levels in plasma were reached by day 4 for alprazolam, 4OH, nefazodone, HO
      nefazodone, mCPP, and dione. Noncompartmental pharmacokinetic analysis showed
      that at steady state, alprazolam Cmax and AUCtau values significantly increased
      approximately twofold and 4OH Cmax and AUCtau values significantly decreased by
      40 and 26%, respectively, when nefazodone was coadministered with alprazolam.
      There was no effect of alprazolam on the single-dose or steady-state
      pharmacokinetics of nefazodone, HO-nefazodone, or dione after the
      coadministration of alprazolam and nefazodone. However, the mean steady-state
      mCPP Cmax and AUCtau significantly increased by approximately threefold and t1/2
      values significantly increased by approximately twofold after the
      coadministration of alprazolam and nefazodone in comparison to those when
      nefazodone was given alone. Competitive inhibition between alprazolam and
      nefazodone metabolism at cytochrome P450 3A4 may be responsible for the
      pharmacokinetic interaction when alprazolam and nefazodone were coadministered.
      No adjustment of nefazodone dosage is required when nefazodone and alprazolam are
      coadministered. Because alprazolam concentrations in plasma are increased in the
      presence of nefazodone, a reduction in alprazolam dosage is recommended when the
      two agents are coadministered.

PMID- 8748429
TI  - Coadministration of nefazodone and benzodiazepines: IV. A pharmacokinetic
      interaction study with lorazepam.
AB  - This study was conducted to determine the potential for an interaction between
      nefazodone (NEF), a new antidepressant, and lorazepam (LOR) after single- and
      multiple-dose administration in a randomized, double-blind, parallel-group,
      placebo-controlled study in healthy male volunteers. A total of 12 subjects per
      group received either placebo (PLA) twice daily, 2 mg of LOR twice daily, 200 mg
      of NEF twice daily, or the combination of 2 mg of LOR and 200 mg of NEF (LOR+NEF)
      twice daily for 7 days. Plasma samples were collected after dosing on day 1 and
      day 7 and before the morning dose on days 4, 5, and 6 for the determination of
      LOR, NEF, and NEF metabolites hydroxy (HO)-NEF, m-chlorophenylpiperazine (mCPP),
      and dione by validated high-performance liquid chromatography methods. Steady
      state levels in plasma were reached by day 4 for LOR, NEF, HO-NEF, mCPP, and
      dione. Noncompartmental pharmacokinetic analysis showed that there was no effect
      of LOR on the single dose or steady-state pharmacokinetics of NEF, HO-NEF, or
      dione after coadministration. The steady-state mCPP Cmax values decreased 36% for
      the LOR+NEF group in comparison to that when NEF was given alone. There was no
      effect of NEF on the pharmacokinetics of LOR after coadministration. The absence
      of an interaction appears to be attributable to LOR's metabolic clearance being
      dependant on conjugation rather than hydroxylation. Overall, no change in LOR or
      NEF dosage is necessary when the two drugs are coadministered.

PMID- 8748430
TI  - Effects of third trimester fluoxetine exposure on the newborn.
AB  - Prospectively identified fluoxetine-exposed pregnancies were evaluated to
      determine whether fluoxetine, a serotonin reuptake inhibitor commonly used for
      the treatment of depression and obsessive-compulsive disorder, might be
      associated with neonatal complications after maternal fluoxetine exposure during
      the third trimester through delivery. The outcomes of all prospectively
      identified, spontaneously reported pregnancies with confirmed fluoxetine exposure
      during the third trimester through delivery were evaluated. Postnatal
      complications unrelated to malformations were reported in 15 of the 112
      identified pregnancies (115 infants), but there was neither a consistent or
      recurring pattern nor a dose relationship. On the basis of this survey and
      comparison with reported rates from the National Hospital Discharge Survey, it is
      unlikely that maternal fluoxetine use during the third trimester results in
      significant postnatal complications.

PMID- 8748431
TI  - Predicting response to fluoxetine in geriatric patients with major depression.
AB  - No consensus exists regarding whether early response to an antidepressant
      strongly predicts a good outcome, what is the criterion for early response, or
      when to measure it. We hypothesized that early response (> or = 20% decrease in
      HAM-d21) after any of weeks 1, 2, or 3 of fluoxetine treatment of major
      depression in geriatric outpatients would predict a favorable outcome by week 6
      or an earlier endpoint accurately enough for clinical use. We also hypothesized
      that the week 1, 2, and 3 percent changes in 21-item Hamilton Rating Scale for
      Depression (HAM-D21) would predict the percent change at week 6 (or endpoint)
      accurately enough for clinical use. We enrolled 671 elderly outpatients with
      unipolar DSM-III-R major depression in a double-blind, placebo-controlled trial
      of fluoxetine, 20 mg/day. For analysis, fluoxetine-treated patients were randomly
      divided into a development set (N = 154) for a preliminary test of our criteria
      and a validation set (N = 181) to validate the development data set's results.
      Early responders at weeks 1, 2, and 3 were statistically significantly more
      likely to experience marked improvement or remission than those lacking early
      response. However, at week 3, this criterion correctly classified only about
      three-fourths of patients with regard to marked improvement and only about two
      thirds with regard to remission. Moreover, about one-third of patients predicted
      to experience marked improvement and about three-fifths of those predicted to
      remit did not. The continuous variable, percent change in HAM-D21, did not
      produce predictive results of any greater clinical utility. We believe that the
      sensitivity, specificity, false-positive rate, false-negative rate, and kappa of
      outcome predictions all should be reported in future studies. Without a full set
      of descriptive statistics, clinicians can be misled by statistically significant
      results.

PMID- 8748432
TI  - A double-blind, placebo-controlled study of a CCK-B receptor antagonist, CI-988,
      in patients with generalized anxiety disorder.
AB  - This multicenter, double-blind, placebo-controlled, parallel-group, randomized
      study assessed the efficacy, safety, and tolerability of a novel CCK-B antagonist
      CI-988 in the treatment of generalized anxiety disorder (GAD). Patients received
      placebo or CI-988 (300 mg/day, thrice daily) for 4 weeks. Patients with a primary
      diagnosis of GAD according to DSM-III-R criteria were randomized. The study
      design included a 1- to 2-week single-blind placebo baseline phase, followed by a
      4-week double-blind treatment phase. Efficacy was measured weekly by Hamilton
      Rating Scale for Anxiety (HAM-A), Clinical Global Impressions of Severity and
      Change, UCLA-Multi Dimensional Anxiety Scale, and Hamilton Rating Scale for
      Depression. Patients were also evaluated to determine whether they met criteria
      for irritable bowel syndrome (IBS) at screening and were evaluated with a
      gastrointestinal visual analog scale at each visit. Eighty-eight patients were
      randomized to CI-988 (N = 45) and placebo (N = 43) at three centers. CI-988 did
      not demonstrate an anxiolytic effect superior to placebo in this clinical trial.
      There was no significant difference in mean change in HAM-A total between placebo
      (-7.73) and CI-988 (-8.64). However, a significant treatment-by-center
      interaction and a highly variable placebo response rate among the three centers
      limit the interpretation of the results. CI-988 did not have an effect on
      symptoms of IBS other than diarrhea, which worsened in patients with IBS. Other
      than a higher incidence of some gastrointestinal symptoms (diarrhea, dyspepsia,
      flatulence, and nausea), CI-988 was well tolerated. Results suggest that testing
      higher oral doses of CI-988 may be warranted.

PMID- 8748433
TI  - Dosing of antidepressants--the unknown art.
AB  - Data from a therapeutic drug monitoring service, in total 2,393 observations in
      1,606 patients, were used to analyze factors associated with the prescribed daily
      doses of the tricyclic antidepressants amitriptyline and nortriptyline. The
      achieved concentrations in plasma were evaluated in relation to suggested
      therapeutic ranges. The doses of both drugs were greatly reduced with increasing
      age, despite the fact that age is of minor importance for their kinetics.
      Interactions with concomitantly given drugs were not handled by dose adjustments
      of the antidepressant. Therapeutic drug monitoring increased the proportion of
      concentrations within the therapeutic range for patients on amitriptyline, but
      not for those on nor-triptyline. The large interindividual kinetic variability
      for most antidepressants requires individualized dosing, but this
      individualization is performed on incorrect grounds.

PMID- 8748434
TI  - Serotonin syndrome in the elderly after antidepressive monotherapy.

PMID- 8748435
TI  - Why can low doses of sulpiride counteract depression?

PMID- 8748436
TI  - Sertraline in stuttering.

PMID- 8748437
TI  - Naltrexone for the treatment of trichotillomania: a case report.

PMID- 8748438
TI  - Exacerbation of psychosis associated with inhaled albuterol.

PMID- 8748439
TI  - Manic episode and ginseng: report of a possible case.

PMID- 8748440
TI  - Case 8: the wambly sophomaniac.

PMID- 8748441
TI  - Economics of publishing.

PMID- 8748442
TI  - An ethicist's commentary on the misdiagnosed radiograph of a racing thoroughbred.

PMID- 8748443
TI  - The pattern of fatal fibrinous pneumonia (shipping fever) affecting calves in a
      large feedlot in Alberta (1985-1988).
AB  - Data from a retrospective field study were used to describe the epidemiology of
      fatal fibrinous pneumonia as it affected beef calves entering a large commercial
      feedlot in southwestern Alberta during the fall months of y 1985 to 1988. A chute
      side computer system was used to record processing and health data on 58885
      calves during this period. The large annual variation (10%-57%) in the proportion
      of total mortality due to fibrinous pneumonia indicated that crude mortality
      cannot be used in epidemiological studies as a surrogate measure of fibrinous
      pneumonia mortality. Yearly epidemic curves for fatal fibrinous pneumonia were
      very similar, with a short time interval (median, 19-22 d) between arrival and
      fatal disease. Fully 75% of the calves that died of fibrinous pneumonia already
      were sick within 2 weeks of arrival. Studies of the biological, environmental,
      and population factors that are present before and shortly after arrival at the
      feedlot are needed to identify strategies for reducing the incidence of fatal
      fibrinous pneumonia.

PMID- 8748444
TI  - The effect of amount of body fat and loss of fat on breeding soundness
      classification of beef bulls.
AB  - Two hundred and fifty-one Aberdeen Angus, Horned Hereford, Polled Hereford, and
      Charolais bulls were examined at the time of sale (sale) and again from 10 to 85
      days later (test) to determine the effect of amount of body fat and loss of fat
      on semen quality. Sale and test measurements included body weight, backfat depth,
      and scrotal circumference. Breeding soundness evaluations were done at test. For
      all bulls, over all years, the positive correlations of body weight loss vs.
      backfat loss, weight loss vs. scrotal circumference loss, and backfat loss vs.
      scrotal circumference loss were highly significant. Aberdeen Angus, Horned
      Hereford, Polled Hereford, and Charolais bulls lost weight at a mean rate of
      1.77, 2.19, 1.94, 1.16 kg per day, respectively, in the interval from sale to
      test. Bulls classified as unsatisfactory lost significantly more weight than
      satisfactory bulls. However, bulls classified as unsatisfactory did not differ
      significantly from satisfactory bulls in the amount of backfat at sale and test
      and in the amount of backfat lost. No significant relationship could be
      demonstrated between increments of backfat and classifications of breeding
      soundness evaluations. Bulls with satisfactory semen quality had significantly
      larger scrotal circumference measurements than those with questionable or
      unsatisfactory classifications. Backfat data at bull sales may be helpful in
      selecting bulls with desirable growth characteristics, as well as reducing the
      risk of purchasing bulls with poor semen quality due to excessive body fat.

PMID- 8748445
TI  - Monocytic leukemia in a horse.

PMID- 8748446
TI  - Silica urolithiasis in a male llama.

PMID- 8748447
TI  - A serological survey of four Leptospira serovars in dairy cows on Prince Edward
      Island.

PMID- 8748448
TI  - Bronchoalveolar lavage in normal cats.

PMID- 8748449
TI  - Esophageal obstruction due to a trichobezoar in a cow.

PMID- 8748450
TI  - Assessment of seropositivity to porcine reproductive and respiratory syndrome
      (PRRS) virus in swine herds in Ontario--1978 to 1982.

PMID- 8748451
TI  - Isolation of a distinct serotype of porcine reproductive and respiratory syndrome
      (PRRS) virus in Ontario.

PMID- 8748452
TI  - Liposarcoma arising from the mandibular bone marrow in a ferret.

PMID- 8748453
TI  - Immunosuppressive drug therapy.

PMID- 8748454
TI  - Allozymic characterization and evolutionary relationships in the Brazilian Akodon
      cursor species group (Rodentia-Cricetidae).
AB  - The present study involved an electrophoretic survey of 22 protein loci in 269
      individuals belonging to three species of the genus Akodon, A. aff. cursor (2n =
      16), A. cursor (2n = 14/15), and A. montensis (2n = 24/25/26), collected in
      Eastern Brazil. The joint results of gene diversity, genetic distances, phenetic
      analyses, and phylogenetic trees suggested that A. aff. cursor has recently
      separated from A. cursor and that the three species have experienced a recent
      chromosomal divergence followed by low allozyme differentiation. These data are
      in agreement with their classification as sibling species.

PMID- 8748455
TI  - Studies on multilocus fingerprints, RAPD markers, and mitochondrial DNA of a
      gynogenetic fish (Carassius auratus gibelio).

PMID- 8748456
TI  - A unique bilirubin-UDP-glucuronosyltransferase deficiency related to neonatal
      jaundice in mice.
AB  - This report describes biochemical and cellular characterization of a spontaneous
      mutation in ICR mice; the mutation has been phenotypically characterized as
      autosomal recessive jaundice in neonates and juveniles and given the gene symbol
      hub (J. Hered. 76:441-446, 1985; Mouse Newslett. 73:28, 1985). The results
      obtained demonstrate that (1) mice homozygous for the mutation are deficient in
      bilirubin-UDP-glucuronosyltransferase activity, and there is no deficiency in
      heterozygous mice, (2) the deficiency is lifelong, even though the clinical
      symptom of jaundice is transitory and restricted to neonates or juveniles, (3)
      bilirubin-UDP-glucuronosyltransferase activity in mutant and nonmutant mice is
      similarly induced by triiodothyronine, (4) glucuronidation and xylodation of
      bilirubin probably occur as the result of separate enzyme forms in mice, and (5)
      Western analysis using antibody to rat bilirubin-UDP-glucuronosyltransferase
      indicates that although there is no electrophoretic mobility difference, there is
      a diffuse band missing in mutant mice. Hepatic hyperplasia, cytomegaly, single
      cell necrosis, and eosinophilic foci are also pleiotropic traits associated with
      homozygous but not heterozygous hub. The hub/hub mouse will be useful in the
      study of substrate specificity and regulation within a complex gene family and,
      perhaps, provide a new and useful animal model for the long-term health effects
      of deficiency in the metabolism of xenobiotics cleared via UDP
      glucuronosyltransferase.

PMID- 8748457
TI  - Specific selection of deoxycytidine kinase mutants with tritiated deoxyadenosine.
AB  - We have shown previously that a low concentration of tritiated deoxyadenosine,
      i.e., 1 microCi/ml, selectively kills wild-type S49 murine lymphoma cells. Mutant
      cells resistant to [3H] deoxyadenosine lacked adenosine kinase completely but
      retained a significant level of deoxyadenosine phosphorylating activity. To study
      further the specificity of [3H] deoxyadenosine selection, lymphoma cell clones
      resistant to 15 microCi/ml [3H] deoxyadenosine have been derived. The resistant
      line, S49-dA15, is also resistant to high levels of nonradioactive deoxyadenosine
      and to deoxyguanosine but remains sensitive to thymidine. The thymidine
      inhibition of the growth of the mutant, in contrast to that of the wild-type
      cells, cannot be prevented by deoxycytidine. The mutant line lacks deoxycytidine
      kinase that also phosphorylates deoxyadenosine. In addition, the mutant cells
      excrete a large amount of deoxycytidine into culture medium, consistent with a
      failure of salvage of the nucleoside in the absence of an appropriate kinase,
      i.e., deoxycytidine kinase. In contrast, a deoxycytidine kinase-deficient cell
      line that was selected with arabinosylcytosine does not excrete deoxycytidine and
      contains high deoxycytidine deaminase activity. [3H] Deoxyadenosine can be used
      as a selective agent for specific selection of deoxycytidine kinase-negative
      mutants.

PMID- 8748458
TI  - Genetic analysis of essential oil variants in Perilla frutescens.
AB  - A new chemotype (C type) of Perilla frutescens (Labiatae) that accumulates trans
      citral as a main component of the essential oil in the leaf was crossed with five
      other chemotypes containing perillaldehyde (PA), elsholtziaketone (EK),
      perillaketone (PK), perillene (PL), and phenylpropanoid (PP) as their respective
      major components for comparison of genetic differences. The analyses of F1 and F2
      progenies showed that trans-citral is accumulated when its metabolism is blocked
      in the simultaneous absence of a dominant gene N, which is involved in the
      conversion of trans-citral into naginataketone via cis-citral, and two polymeric
      genes Fr1 and Fr2, which are involved in the conversion of trans-citral into
      perillene. On the basis of new data obtained from various intercrosses involving
      the C type as one of the parents, the genotypes of different chemotypes as well
      as the sites of action of several genes controlling reaction steps in the
      biosynthesis of monoterpenes in Perilla have been revised.

PMID- 8748459
TI  - Alcohol dehydrogenase (ADH) isozymes in the AdhN/AdhN strain of Peromyscus
      maniculatus (ADH-deermouse) and a possible role of class III ADH in alcohol
      metabolism.
AB  - Although the AdhN/AdhN strain of Peromyscus maniculatus (so-called ADH-
      deermouse) has been previously considered to be deficient in ADH, we found ADH
      isozymes of Classes II and III but not Class I in the liver of this strain. On
      the other hand, the AdhF/AdhF strain (so-called ADH+ deermouse), which has liver
      ADH activity, had Class I and III but not Class II ADH in the liver. In the
      stomach, Class III and IV ADHs were detected in both deermouse strains, as well
      as in the ddY mouse, which has the normal mammalian ADH system with four classes
      of ADH. These ADH isozymes were identified as electrophoretic phenotypes on the
      basis of their substrate specificity, pyrazole sensitivity, and immunoreactivity.
      Liver ADH activity of the ADH- strain was barely detectable in a conventional ADH
      assay using 15 mM ethanol as substrate; however, it increased markedly with high
      concentrations of ethanol (up to 3 M) or hexenol (7 mM). Furthermore, in a
      hydrophobic reaction medium containing 1.0 M t-butanol, liver ADH activity of
      this strain at low concentrations of ethanol (< 100 mM) greatly increased (about
      sevenfold), to more than 50% that of ADH+ deermouse. These results were
      attributable to the presence of Class III ADH and the absence of Class I ADH in
      the liver of ADH- deermouse. It was also found that even the ADH+ strain has low
      liver ADH activity (< 40% that of the ddY mouse) with 15 mM ethanol as substrate,
      probably due to low activity in Class I ADH. Consequently, liver ADH activity of
      this strain was lower than its stomach ADH activity, in contrast with the ddY
      mouse, whose ADH activity was much higher in the liver than in the stomach, as
      well as other mammals. Thus, the ADH systems in both ADH- and ADH+ deermouse were
      different not only from each other but also from that in the ddY mouse; the ADH-
      strain was deficient in only Class I ADH, and the ADH+ strain was deficient in
      Class II ADH and down-regulated in Class I ADH activity. Therefore, Class III
      ADH, which was found in both strains and activated allosterically, may
      participate in alcohol metabolism in deermouse, especially in the ADH- strain.

PMID- 8748460
TI  - Group B streptococcal meningitis presenting as stroke in a nondebilitated man.
AB  - An unusual case of group B streptococcal meningitis in an adult is described. The
      evidence presented suggests that early vascular involvement during the meningitic
      process resulted in cerebral infarction, thereby explaining the patient's sudden
      deterioration and atypical presentation.

PMID- 8748461
TI  - Spinal and epidural endoscopy: a historical review.

PMID- 8748462
TI  - Epidural endoscopy-aided drug delivery: a case report.

PMID- 8748463
TI  - The effect of supplemental beta-carotene on immunologic indices in patients with
      AIDS: a pilot study.
AB  - Patients with the acquired immunodeficiency syndrome (AIDS) are characterized by
      a decrease in the number of T helper cells, a defect that is linked to the
      impaired immunologic competence. Vitamin A and its dietary precursor, beta
      carotene, increase absolute T helper cell counts as well as indices of T cell
      function in both human and animal models. To determine if short-term beta
      carotene treatment affects T lymphocyte subsets in patients with AIDS, a single
      blind, non-randomized clinical trial of beta-carotene was performed in seven
      patients with AIDS. Enrollment criteria included no evidence of: a) active
      opportunistic infection: b) greater than 1 kilogram change in weight in the month
      preceding enrollment; c) chronic diarrhea or malabsorption; and d) hepatic
      disease or significant anemia. Beta-carotene was given with meals in two divided
      doses of 60 mg/day for four weeks; this was followed by no therapy for six weeks.
      Samples for total white blood cell, lymphocyte and T lymphocyte subset counts
      were measured at baseline, at the end of four weeks of treatment and another six
      weeks after treatment had stopped. P24 antigen, beta-2 microglobulin and liver
      function tests were also measured. All subjects tolerated the treatment well
      without evidence of toxicity. In response to beta-carotene, total lymphocyte
      counts rose by 66 percent (.05 < p < .10), and CD4+ cells rose slightly, but
      insignificantly, in the entire group. In all three of the patients who had
      baseline CD4+ cells greater than 10/microliters, however, the mean absolute
      increase in CD4+ cells in response to beta-carotene was 53 +/- 10
      cells/microliters (p < .01). Six weeks off beta-carotene treatment, the absolute
      CD4+ cell count returned to pretreatment levels (p < .01). No change was observed
      in CD8+ cells. P24 antigen and beta-2 microglobulin did not change during
      treatment. These preliminary observations suggest that short-term treatment with
      beta-carotene may increase CD4+ cell counts in patients with AIDS who have
      greater than 10 cells/microliters.

PMID- 8748464
TI  - Proton magnetic resonance spectroscopy of the left medial temporal and frontal
      lobes in chronic schizophrenia: preliminary report.
AB  - Proton magnetic resonance spectroscopy (MRS) was performed in 30 medicated
      schizophrenic patients and 30 normal subjects. Two groups, each containing 15
      schizophrenic patients and 15 age-and sex-matched normal subjects, received MRS
      examinations for different volumes of interest, either the frontal lobe or the
      medial temporal lobe. Schizophrenic patients showed a decrease in the ratios of N
      acetylaspartate (NAA)/choline-containing compounds (Cho) and NAA/creatine
      phosphocreatine (Cr). The patients also showed an increase in the ratio of Cho/Cr
      in the left medial temporal lobe but not in the left frontal lobe. The age at
      onset of illness correlated positively with the ratios of NAA/Cho and NAA/Cr in
      the medial temporal lobe. No significant correlation was observed between the
      ratios of NAA/Cho, NAA/Cr, or Cho/Cr in the left medial temporal and frontal
      lobes and clinical symptomatology as assessed by the Scale for the Assessment of
      Negative Symptoms and the Positive and Negative Syndrome Scale.

PMID- 8748465
TI  - Cingulate gyrus in schizophrenic patients and normal volunteers.
AB  - Comparable magnetic resonance imaging (MRI) sections of right and left anterior
      and posterior cingulate gyrus were measured blindly with a method developed by
      the authors in 14 patients with schizophrenia (by DSM-III-R criteria) and 14
      normal volunteers individually matched to the patients for age, sex, education,
      and parental socioeconomic status. Interrater reliability met or exceeded 0.92
      (k) on all cingulate structures measured. Brain volume in the two groups differed
      by 2% (normal > schizophrenia), but the difference was not significant. All
      cingulate gyri measures were nonsignificantly smaller in the patient group by 3
      5%. There was an inverse correlation between left anterior cingulate size and
      severity of hallucinations that was, however, not significant after Bonferroni
      correction. Lateral asymmetry of the cingulate regions measured was the same in
      both groups, with the left being nonsignificantly smaller than the right for all
      regions. We demonstrate a reliable method, unreported thus far in the literature,
      to measure the cingulate gyrus on MRI; the results suggest that left cingulate
      gyrus size may be inversely related to severity of hallucinations in
      schizophrenia.

PMID- 8748466
TI  - Caudate, putamen, and globus pallidus volume in schizophrenia: a quantitative MRI
      study.
AB  - Basal ganglia structures have been reported to be abnormal in schizophrenia.
      However, while component structures of the basal ganglia are functionally
      differentiated, there have been no evaluations of their separate magnetic
      resonance imaging (MRI) volumes with small voxel (1.5 mm3) spoiled gradient
      recalled acquisition in steady state techniques and multi-plane assessments. We
      examined MRI scans from 15 male, right-handed, neuroleptic-medicated
      schizophrenic patients and 15 age-, handedness-, and gender-matched normal
      volunteers. Compared with normal subjects, schizophrenic patients showed enlarged
      volumes: 14.2% for total basal ganglia, 27.4% for globus pallidus, 15.9% for
      putamen, and 9.5% for caudate. Increased volumes, especially of the caudate, were
      associated with poorer neuropsychological test performance on finger tapping and
      Hebb's Recurring Digits. These findings indicate abnormalities throughout all
      basal ganglia structures in at least a subgroup of schizophrenic patients.

PMID- 8748467
TI  - A single photon emission computed tomography study of cerebral regional perfusion
      changes induced by a learning task in subjects with mild memory impairment.
AB  - Fifteen nondemented subjects with memory complaints underwent serial single
      photon emission computed tomography (SPECT) studies with technetium-99m-d, l
      hexamethyl-propylene amine oxime (HMPAO) as tracer. Scans were carried out under
      a baseline conditions and during the learning phase of the Memory Efficiency
      Profile (MEP), a combined visual perception and memory task developed by Rey.
      Results indicate a positive correlation between activation, as indexed by HMPAO
      uptake, and neuropsychological assessment. Right temporal activation was
      correlated with MEP immediate recall. The right cerebellum was correlated with
      both MEP immediate and delayed recall. This study suggests that SPECT can show
      cortical activation during cognitive performance in subjects with mild memory
      impairment.

PMID- 8748468
TI  - Brain glucose metabolism in violent psychiatric patients: a preliminary study.
AB  - Positron emission tomography with 18F-deoxyglucose was used to evaluate regional
      brain glucose metabolism in eight normal subjects and eight psychiatric patients
      with a history of repetitive violent behavior. Seven of the patients showed
      widespread areas of low brain metabolism. Although the location of the abnormal
      regions varied among patients, they showed significantly lower relative metabolic
      values in medial temporal and prefrontal cortices than did normal comparison
      subjects. These regions have been implicated as substrates for aggression and
      impulsivity, and their dysfunction may have contributed to the patients' violent
      behavior.

PMID- 8748469
TI  - Schizophrenic auditory hallucinations are associated with increased regional
      cerebral blood flow during verbal memory activation in a study using single
      photon emission computed tomography.
AB  - Single photon emission tomography with split-dose technetium-99m-d, l-hexamethyl
      propylene amine oxime was used to measure regional cerebral blood flow (rCBF)
      during a memory-activation paradigm in a group of 18 medicated DSM-III-R
      schizophrenic patients. The relationship between clinical features of
      schizophrenia and rCBF patterns was examined. Increased blood flow to the left
      basal ganglia was revealed during activation in patients reporting hallucinations
      in the previous month, a finding that was not influenced by medication dose or
      other confounding variables. This result adds to previous functional imaging
      studies that have related basal ganglia abnormalities to hallucinatory phenomena
      and suggests that left basal ganglia hyperactivity may be relevant to an internal
      monitoring deficit responsible for the appearance of those symptoms in
      schizophrenia.

PMID- 8748470
TI  - Mood effects on limbic blood flow correlate with emotional self-rating: a PET
      study with oxygen-15 labeled water.
AB  - Positron emission tomography was used to study the effects of experimentally
      controlled mood states on cerebral blood flow (CBF), measured with the
      quantitative equilibrium infusion method and 15O-labeled water. Twenty-seven
      brain regions in each hemisphere were assessed in 16 normal subjects. CBF and
      heart rate were measured during happy and sad mood induction, and during two
      nonemotional control conditions: sex differentiation and resting baseline.
      Valence-specific effects of mood on CBF were obtained for subcortical, but not
      for frontal-temporal or control regions. CBF increased in left amygdala and
      decreased in right amygdala during sad mood relative to the averaged control
      conditions. These changes correlated with shifts toward negative affect.
      Correlations were opposite for subcortical (negative affect associated with lower
      left hemispheric CBF) compared with frontal-temporal cortical regions. Results
      support limbic involvement in regulating emotional states and suggest some
      reciprocity between subcortical and frontal-temporal regulation of emotional
      experience.

PMID- 8748471
TI  - Occupancy of striatal dopamine D2 receptors.

PMID- 8748472
TI  - Toward a more comprehensive medical anthropology: the case of adolescent
      psychopathology.
AB  - This article argues for a more comprehensive analytical approach in medical
      anthropology than is currently followed, one that combines attention to
      structural factors (political, economic, medical/psychiatric),
      experiential/symbolic expressions and meanings, and biological/bodily features of
      disorders. We show how subject matter that may be defined as "adolescent
      psychopathology" would be better understood by a comprehensive approach than by
      partial views. Three areas within adolescent psychopathology are chosen as
      illustrative: anorexia nervosa, dissociation, and social aggression. Each of
      these, like adolescence itself, is powerfully shaped by historical and
      contemporary cultural influences, and each implicates important theories in
      medical anthropology.

PMID- 8748473
TI  - Clown doctors: shaman healers of Western medicine.
AB  - The Big Apple Circus Clown Care Unit, which entertains children in New York City
      hospitals, is compared with non-Western healers, especially shamans. There is not
      only superficial resemblance--weird costumes, music, sleight of hand,
      puppet/spirit helpers, and ventriloquism--but also similarity in the meanings and
      functions of their performances. Both clown and shaman violate natural and
      cultural rules in their performances. Both help patient and family deal with
      illness. Both use suggestion and manipulation of medical symbols in attempting to
      alleviate their patients' distress. Just as traditional ethnomedical systems have
      been integrated with Western medicine in other societies, clown doctors can
      provide complementary therapy that may enhance the efficacy of medical treatment
      in developed nations, particularly for children.

PMID- 8748474
TI  - Changes in clinical practice in response to reductions in reimbursement:
      physician autonomy and resistance to bureaucratization.
AB  - This analysis of field data from 1991 and 1992 examines the process of joint
      decision making between cardiothoracic surgeons and anesthesiologists in a U.S.
      hospital as they made changes in clinical practice in response to reimbursement
      reductions. Although these physicians have concurrent responsibility for patient
      care in the operating room, their domains of authority are ambiguous. Much
      clinical decision making was found to be based on charismatic authority. In
      making practice changes, cardiothoracic surgeons maintained all and
      anesthesiologists most of their charismatic authority, expanding the conventional
      range of physician practice while prescribing specific practices for nonphysician
      providers. Ambiguity of joint physician authority over patient care was left
      unresolved, and the economic goals of the practice changes were not realized.
      Physicians resisted the bureaucratic claim to authority rooted in cost accounting
      by resorting to the need for nonroutinized clinical decisions.

PMID- 8748475
TI  - Medical pluralism in the United States: a review.

PMID- 8748476
TI  - Mohawk English in the medical interview.
AB  - Mohawk English uses metalinguistic cues that reflect Iroquoian grammatical and
      sociolinguistic patterning. Although phrases like "It seems to me" are common in
      many varieties of English, Mohawk English speakers use these words and phrases in
      subtly different ways from other speakers of English. These differences could
      lead to misinterpretation by health care providers.

PMID- 8748477
TI  - MR measurement of time-dependent blood pressure variations.
AB  - An MR imaging method for measuring intravascular pressure variations is
      introduced. The technique is based on estimates of vascular compliance and vessel
      distension, which are obtained from a correlation of spatial and temporal
      velocity derivatives and measurements of the velocity gradient in the direction
      of flow, respectively. The accuracy of the technique was determined in vitro
      through a comparison of MR and transducer pressure measurements obtained in
      distensible vessel phantoms undergoing pulsatile flow. Results indicated that a
      root-mean-square error of 4-12% can be expected in phantoms covering a
      physiological range of compliance. In vivo feasibility was demonstrated by
      thoracic aorta pressure measurements, which produced pressure waveforms with an
      expected shape and magnitude.

PMID- 8748478
TI  - A velocity correlation method for measuring vascular compliance using MR imaging.
AB  - A method for estimating vascular compliance using MR velocity imaging is
      presented. The technique combines an analysis of pulse propagation, based on
      spatially averaged equations of continuity and momentum, together with phase
      contrast velocity measurements to estimate the compliance from a correlation of
      second-order spatial and temporal velocity derivatives. The technique can be
      applied in the presence of reflected flow waves and uses velocity data acquired
      throughout the entire cardiac cycle. The accuracy of the technique was assessed
      in distensible vessel phantoms spanning a physiological range of compliance
      through a comparison with compliance estimates obtained using high-resolution MR
      imaging and pressure transducers. The mean error of all measurements was found to
      be 0.04 +/- 0.02% per mm Hg, with the relative errors ranging from 1.2% to 46%.
      Error was found to decrease as the temporal sampling rate and/or image plane
      separation were increased. This suggests that an accurate hemodynamic evaluation
      of a vessel's elastic properties is feasible with MR velocity imaging techniques.

PMID- 8748479
TI  - Measurement of regional aortic compliance by MR imaging: a study of
      reproducibility.
AB  - The reproducibility of MR imaging for the measurement of aortic compliance was
      studied in 47 healthy volunteers. Long and short term reproducibility and
      intraobserver variability were tested. The method was modified to improve image
      quality and short term reproducibility and intraobserver variability retested.
      For comparison, spin echo imaging was compared with cine gradient echo imaging.
      Initial long term reproducibility showed a mean difference (+/-SE) of 3% (+/- 7%)
      with 95% confidence interval (CI) for limits of agreement of +/- 69%. Short term
      reproducibility (7% +/- 6%, 95% CI +/- 46%) and intraobserver variability (1% +/-
      2%, 95% CI +/- 31%) were better. After modification of the technique and
      optimization of image quality, both short term reproducibility and intraobserver
      variability improved (0% +/- 3%, 95% CI +/- 17% and 5% +/- 2%, 95% CI +/- 16%
      respectively). Aortic compliance can be measured using spin echo MR imaging with
      good reproducibility provided care is taken to obtain good quality images with
      high spatial resolution.

PMID- 8748480
TI  - Determination of wall shear stress in the aorta with the use of MR phase velocity
      mapping.
AB  - MR phase velocity mapping was used to calculate wall shear stress (WSS) in the
      suprarenal and infrarenal abdominal aorta, two sites with very different
      proclivities for development of a atherosclerosis. For the eight subjects
      studied, the average value of the mean (time averaged over the cardiac cycle) WSS
      in the suprarenal aorta was 10.4 dynes/cm2 at the posterior wall and 8.6 at the
      anterior wall. In the infrarenal aorta, WSS values were 4.7 at the posterior wall
      and 6.1 at the anterior wall. Peak WSS over the cardiac cycle was 48 and 54 at
      the anterior and posterior walls of the suprarenal aorta, respectively, and 33
      and 30 at the anterior and posterior walls of the infrarenal aorta, respectively.
      Wide variation was found in both mean and peak WSS values among subjects.
      However, for 28 of 32 locations examined, mean and peak WSS were higher in the
      suprarenal aorta than in the infrarenal aorta. Because atherosclerosis is more
      likely to form in the infrarenal aorta than in the suprarenal aorta, this study
      supports the hypothesis that low WSS is a localizing factor for atherosclerosis,
      and high WSS may act as a deterrent against formation of atherosclerosis.

PMID- 8748481
TI  - Phase-contrast echo-planar MR imaging: real-time quantification of flow and
      velocity patterns in the thoracic vessels induced by Valsalva's maneuver.
AB  - Although the clinical manifestations of Valsalva's maneuver are well known, the
      associated hemodynamic changes in the great vessels have not been extensively
      studied and documented. In each of six healthy subjects, we evaluated three
      "quasi-steady-state" phases of Valsalva's maneuver: (1) during normal
      respiration, (2) during late strain, and (3) 4 seconds after strain release.
      Continuous flow, velocity, and cross-sectional area measurements were obtained in
      the superior vena cava, pulmonary trunk, and thoracic aorta with single-shot echo
      planar MR imaging (EPI) with velocity-encoded gradients, which provided 256
      images in 5 seconds, yielding 26 velocity-encoded images per second. In the
      superior vena cava, Valsalva's maneuver induced an 11% decrease in average flow
      volume, a 102% increase in peak flow velocity, a 156% increase in the time
      velocity integral, and a 37% decrease in cross-sectional area. MR velocity
      measurements agreed with echocardiographic data and supplied additional
      information on flow and morphology. EPI showed a reduction in venous return
      during Valsalva's maneuver by simultaneously assessing flow, velocity, and vessel
      morphology; this technique appears to be useful in the analysis of flow dynamics
      of the great vessels.

PMID- 8748482
TI  - Flow quantitation with echo-planar phase-contrast velocity mapping: in vitro and
      in vivo evaluation.
AB  - We present a multishot echo-planar imaging (EPI) phase-contrast implementation
      for flow quantitation. The measurement accuracy of this technique was evaluated
      in vitro and in vivo. A gated eight-shot EPI phase-contrast sequence (TR/TE =
      16/7.4, 45 degrees flip angle), with a flow-phase interval of 32 msec and an in
      plane resolution of 2 x 2 mm was initially evaluated in a pulsatile flow phantom.
      Subsequently, EPI phase-contrast flow measurements of the ascending and
      descending aorta, obtained in 10 volunteers, were compared with flow volume data
      acquired with a conventional cine phase-contrast sequence (TR/TE = 24/7, 45
      degrees flip angle, 48-msec flow-phase interval, 2 x 1 mm in-plane resolution).
      Comparisons between flow measurements were made using data obtained with the flow
      probe and cine phase contrast as the standard of reference for in vitro and in
      vivo measurements, respectively. EPI phase-contrast sequences reduced data
      acquisition times tenfold compared with cine phase-contrast sequences. EPI phase
      contrast flow measurements correlated well with phantom flow (r = .98, slope =
      1.1) as well as with aortic cine phase-contrast flow volume determinations (r =
      .98). A 95% confidence interval of measurement differences between echo-planar
      and cine phase-contrast imaging, ranging from 2.0 to -1058 mL/min was computed.
      Ultrafast phase-contrast flow measurements are possible. Multishot EPI phase
      contrast imaging provides high measurement accuracy in pulsatile vessels while
      keeping the image acquisition interval short enough to be accomplished in a
      comfortable breath-hold.

PMID- 8748483
TI  - Validation of volume flow measurements with cine phase-contrast MR imaging for
      peripheral arterial waveforms.
AB  - A flow phantom was used to study MR volume flow measurements for monophasic and
      triphasic waveforms over the flow range expected in peripheral arteries at rest
      and with exercise (2-24 mL/sec, n = 50). The improvement in accuracy with phase
      correction image processing to eliminate errors caused by eddy currents was
      measured. Volume flow estimates with Doppler sonography were also measured. MR
      volume flow measurements correlated with volume collection with r = .996 and mean
      error = 4.6%. Phase-correction processing decreased mean error from 12.6% to 4.6%
      (P < .001, paired t-test). Doppler sonography had a higher mean error of 10.3% (P
      < .001, unpaired t-test). Cine phase-contrast MR imaging provides accurate
      estimates of volume blood flow for waveforms and flow ranges expected in
      peripheral arteries.

PMID- 8748484
TI  - Renal artery velocity mapping with MR imaging.
AB  - An MR phase imaging sequence with a very short echo time was used to assess blood
      velocity and flow at the renal artery bifurcation. Cardiac-gated MR imaging data
      were obtained in six healthy subjects in sagittal planes adjacent to the
      abdominal aorta and transverse planes above and below the renal artery
      bifurcation. Average renal artery flow rate was 23.8 +/- 9 mL/sec. A strong
      individual variability was found for the velocity profiles in the abdominal aorta
      during end-systolic regurgitation. Flow rate was also determined in three
      patients with reduced renal artery blood flow. Two patients received therapy with
      percutaneous transluminal angioplasty. The successful outcome was documented with
      MR imaging. A reliable assessment of renal artery flow with MR phase imaging is
      feasible. Measurement of the velocity profiles yields valuable insights in the
      complicated flow regime at the renal artery bifurcation.

PMID- 8748485
TI  - Comparison of phantom and computer-simulated MR images of flow in a convergent
      geometry: implications for improved two-dimensional MR angiography.
AB  - The signal loss that occurs in regions of disturbed flow significantly decreases
      the clinical usefulness of MR angiography in the imaging of diseased arteries.
      This signal loss is most often attributed to turbulent flow; but on a typical MR
      angiogram, the signal is lost in the nonturbulent upstream region of the stenosis
      as well as in the turbulent downstream region. In the current study we used a
      flow phantom with a forward-facing step geometry to model the upstream region.
      The flow upstream of the step was convergent, which created high levels of
      convective acceleration. This region of the flow field contributes to signal loss
      at the constriction, leading to overestimation of the area of stenosis reduction.
      A computer program was designed to simulate the image artifacts that would be
      caused by this geometry in two-dimensional time-of-flight MR angiography.
      Simulated images were compared with actual phantom images and the flow artifacts
      were highly correlated. The computer simulation was then used to test the effects
      of different orders of motion compensation and of fewer pixels per diameter, as
      would be present in MR angiograms of small arteries. The results indicated that
      the computational simulation of flow artifacts upstream of the stenosis provides
      an important tool in the design of optimal imaging sequences for the reduction of
      signal loss.

PMID- 8748486
TI  - Cardiac imaging: comparison of two-shot echo-planar imaging with fast segmented K
      space and conventional gradient-echo cine acquisitions.
AB  - We compared the cardiac image quality of multishot echo-planar imaging (EPI),
      segmented K-space, and conventional cine acquisitions. Three techniques were used
      to obtain gated multiphase acquisitions of an axial section traversing both
      ventricles in 10 volunteers: two-shot EPI acquired nonsequentially over two heart
      beats breath-held; segmented K-space cine with eight K-space lines acquired per
      cardiac trigger over 16 R-R intervals, also breath-held; and 24 cine phases
      obtained over 256 R-R intervals. Intraventricular SNRs with two-shot EPI were
      superior to segmented K-space cine acquisitions (P < .005) and not statistically
      different from conventional cine acquisitions (P < .1). Intraventricular signal
      was most homogeneous on conventional cine images (P < .05). Coronary artery
      visualization and myocardial delineation were better on the EPI image set than on
      segmented K-space cine images (P < .05). Two-shot EPI provides high-quality gated
      cardiac images with an acquisition time of only 2 seconds.

PMID- 8748487
TI  - Dynamic contrast-enhanced MR imaging evaluation of osteosarcoma response to
      neoadjuvant chemotherapy.
AB  - Assessment of osteosarcoma response to neoadjuvant chemotherapy has prognostic
      implications, but conventional imaging techniques have been unable to provide an
      accurate quantitative measure of tumor response. We developed an analysis of
      dynamic contrast-enhanced MR imaging (DEMRI) to render an image of dynamic vector
      magnitudes (DVM) and to summarize the result in a quantitative parameter, mean
      DVM for the lesion (mu DVM). We compared the mu DVM from the examination before
      surgery with histologic results from an en bloc resection of the tumor in 19
      cases. The final mu DVM value provided an accurate (89.5%) measure of tumor
      necrosis in osteosarcoma. Further, we analyzed the findings in 17 patients with
      osteosarcoma who completed three DEMRI examinations during the course of therapy.
      Tumors with higher mu DVM values at presentation had greater decreases in the
      parameter over the course of therapy. These results are consistent with the
      distribution of DVM values in these lesions serving as an indicator of tumor
      perfusion and a possible surrogate variable for drug delivery.

PMID- 8748488
TI  - Changes in fibroglandular volume and water content of breast tissue during the
      menstrual cycle observed by MR imaging at 1.5 T.
AB  - MR imaging at 1.5 T was used to investigate variations in breast parenchyma
      during the menstrual cycle. Seven subjects were examined twice weekly over at
      least one menstrual cycle. A three-point Dixon technique (TE = 19 msec, TR = 2000
      msec) provided images of fat, water, and static magnetic field (Bo), from which
      two quantitative whole breast parameters were calculated: the mean relative
      volumetric water content, <WC>, and the mean volumetric fibroglandular fraction,
      <FV>. Four of seven subjects showed unequivocal cyclic variations in <WC> and
      <FV> consistent with expected histologic changes; <WC> and <FV> values were
      elevated during menses and reduced in mid-cycle. The maximum deviation measured
      for each of the four subjects was < or = 10% in <WC> and <FV> units. These
      variations probably do not influence significantly the clinical interpretation of
      unenhanced MR breast images. Quantitative measurements of breast parenchyma,
      however, should recognize these effects.

PMID- 8748489
TI  - Persistent/recurrent hyperparathyroidism: a comparison of sestamibi scintigraphy,
      MRI, and ultrasonography.
AB  - For patients with persistent or recurrent hyperparathyroidism, parathyroid
      imaging is indicated to confirm the presence of abnormal parathyroid gland(s) and
      identify their location. These imaging techniques are being modified constantly
      and newer methods have been developed. Sestamibi scintigraphy, MRI and sonography
      were compared in 23 patients with persistent or recurrent hyperparathyroidism.
      Preoperative 99m-Technetium Sestamibi (MIBI), MRI and ultrasonographic (US)
      studies of 23 patients with 25 histopathologically confirmed abnormal parathyroid
      glands were compared, using independent prospective interpretations. All patients
      had been operated upon previously for hyperparthytroidism. Accuracy of various
      combinations of MRI, MIBI, and US also were calculated. The results are shown for
      all abnormal glands (n =25); sensitivities and accuracies were 88 and 84% for
      MRI, 80 and 80% for MIBI, and 58 and 44% for US. For only parathyroid adenomas (n
      = 18), sensitivities and accuracies were 89 and 89% for MRI, 94 and 94% for MIBI,
      and 58 and 39% for US. Finally, for parathyroid hyperplasia (n = 7 glands in five
      patients), sensitivities and accuracies were 83 and 71% for MRI, 43 and 43% for
      MIBI, and 57 and 57% for US. Either MIBI or MRI results were significantly better
      for detecting abnormal parathyroid glands than US (P < 0.01), but MRI and MIBI
      were not statistically different. Combining MRI and MIBI produced a combined
      accuracy of 92%, whereas combining either of these tests with US did not improve
      on the accuracy of either test alone. In conclusion, for patients with persistent
      or recurrent hyperparathyroidism, MRI and MIBI are equally accurate for detecting
      abnormal parathyroid glands, and the combination of both tests may be more
      accurate than either test alone.

PMID- 8748490
TI  - Fast spin-echo characteristics of visual stimulation-induced signal changes in
      the human brain.
AB  - A fast spin-echo (FSE) technique used in a conventional MR imaging scanner has
      been successfully developed for obtaining functional MR images with high spatial
      resolution and multiple slices. Our preliminary visual stimulation studies using
      the FSE technique show that the nuclear MR signal increases by 2.6% during
      activation in the primary visual cortex. These results provide evidence that the
      diffusion of tissue water molecules plays a key role in determining functional MR
      signal amplitude. Because the FSE functional MR imaging signal is extremely
      sensitive to microvascular (brain capillaries) hemodynamics, the FSE technique
      can be a powerful tool for studying the neuronal activity of the human brain.

PMID- 8748491
TI  - Cocaine-induced changes in time course of regional cerebral blood volume and
      transit time as determined by dynamic MR imaging.
AB  - We examined cocaine-mediated change in regional cerebral blood volume (rCBV) and
      mean transit time (MTT) in central brain structures of rats using functional MR
      imaging techniques. Changes in MTT and rCBV in animals who had previously been
      given cocaine depended on the length of time between the last pretreatment
      injection and the acute injection and seemed to parallel cocaine-mediated changes
      in extracellular dopamine concentrations.

PMID- 8748492
TI  - Paramagnetic polymerized liposomes as new recirculating MR contrast agents.
AB  - We describe a well-tolerated blood pool contrast agent with extended
      recirculatory half-life based on paramagnetic polymerized liposomes (PPLs). PPLs
      were constructed from a new type of polymerizable lipid molecule that has a
      derivative of gadopentetate dimeglumine as the hydrophilic head group and
      diacetylene groups in the hydrophobic acyl chains, which cross-link when
      irradiated with ultraviolet (UV) light. Biodistribution, blood pool half-life,
      and MR image enhancement were determined for PPLs composed of 10% of the
      gadopentetate dimeglumine lipid and 90% of ditricosadiynoyl tricosadiynayl
      phosphatidylcholine (DAPC) at a dose of 0.015 mmol Gd+3/kg in rats. In T1-weighed
      MR images (TR/TE = 400/18 msec), an average signal enhancement of 34% in the
      kidneys and 20% in the liver was observed, which persisted for at least 90
      minutes after administration of the PPLs. Biodistribution studies using
      radiolabeled PPLs confirmed that 80% of the injected dose remained in the blood
      pool after 2 hours. The half-life of elimination from the blood pool was 19
      hours. The preparation was well tolerated in rats and produced similar MR
      contrast enhancement of the blood pool as produced by other liposome contrast
      agents. However, the half-life of PPL elimination from the blood pool was
      prolonged relative to other liposome systems.

PMID- 8748493
TI  - Nuclear magnetic relaxation dispersion studies of water-soluble gadolinium(III)
      texaphyrin complexes.
AB  - Water proton 1/T1 nuclear magnetic relaxation dispersion (NMRD) profiles were
      measured for a water-soluble gadolinium(III) texaphyrin (Gd-tex) complex as a
      function of temperature and in the presence and absence of 5% human serum albumin
      (HSA). Upon dissolving the complex in water (0.259 mM), the water relaxivity
      values decreased with time but remained higher than those of free GD3+(aq) at all
      fields. Concurrent measurements of free Gd3+ using metallochromic dyes indicated
      that demetallation of the texaphyrin did not occur over a period of several days
      at 37 degrees C. The high relaxivity values and shape of the NMRD profile of this
      complex may be ascribed to a combination of large water coordination number (q
      estimated at 3.5) and long tau R. Upon mixing an aqueous solution of the complex
      with 5% HSA, the low-field water relaxivity slightly decreased whereas the high
      field relaxivity increased relative to the free complex in water, and the
      relaxivities became nearly independent of temperature. These observations
      indicate that water exchange between the inner coordination sphere of Gd-tex and
      bulk water becomes limiting in the presence of HSA.

PMID- 8748494
TI  - MR imaging of hepatic nodular regenerative hyperplasia.
AB  - Nodular regenerative hyperplasia (NRH), a rare condition that is commonly
      associated with noncirrhotic portal hypertension, is not well described in the MR
      literature. Three patients at two institutions were identified who had both
      abdominal MR imaging and pathologic evidence of NRH. All examinations were
      performed at 1.5 T and included axial T1- and T2-weighted spin-echo (SE) images.
      The MR studies were reviewed by two radiologists in consensus. Two patients had
      multiple liver lesions that had high signal components on T1-weighted images and
      were predominantly isointense with liver on the T2-weighted images. One patient
      had no focal lesions identified. NRH, when visualized on MR images, appears as
      multifocal masses with shortened T1 and T2 similar to liver. NRH should be
      considered in the differential diagnosis of hepatocellular tumors, especially in
      patients with a predisposing condition.

PMID- 8748495
TI  - Visualizing tissue compliance with MR imaging.
AB  - We propose a method for visualizing the mechanical properties of tissue based on
      the use of periodic mechanical compression in conjunction with phase-contrast MR
      imaging. A specialized mechanical transducer was used to provide programmable
      compression pulses to the surface of compliant phantoms. These compression pulses
      were synchronized to a spin-echo sequence with motion-sensitizing gradients to
      generate phase information reflecting spin displacement throughout the phantom.
      This sequence was tested with two agarose gel phantoms. The first was a cylinder
      containing three parallel layers of varying compliance and the second was
      composed of a semirigid sphere suspended in a uniform layer of decreased elastic
      modulus. Images showed complex patterns of motion throughout the phantom, which
      correlated with expected motion behavior of the phantom structures. This
      indicates that the biomechanical properties of tissues may be elucidated through
      the use of motion-sensitized MR imaging and suggests that a form of image
      contrast relating to tissue elasticity may be feasible.

PMID- 8748496
TI  - Automated shimming at 1.5 T using echo-planar image frequency maps.
AB  - Using echo-planar imaging, we developed an automated image-based procedure to
      shim the static (B0) field. Our method uses the rapid acquisition capability of
      echo-planar imaging to collect the required frequency data rapidly, rendering the
      shim data acquisition time negligible in comparison with the total study time. We
      address image distortion issues involved in echo-planar imaging acquisition of
      the data and formulate analytic methods for arriving at an optimal shim for the
      NMR imaging experiment in a single iteration. We investigated the use of cost
      functions other than least-squares (Chebychev, high-order numeric) and found that
      choice between the cost functions we tested was irrelevant to resultant image
      quality, at least when used in conjunction with low-order shims. With appropriate
      integration, the method has become routine practice for investigators at our
      laboratory.

PMID- 8748497
TI  - Functional MR imaging using gradient-echo echo-planar imaging in the presence of
      large static field inhomogeneities.
AB  - At 1.5 T, the field strength of most clinical MR imagers, gradient-echo imaging
      is the primary imaging method for measuring brain activation, as such sequences
      are highly sensitive to changes in blood oxygenation or T2* effects.
      Unfortunately, gradient-echo sequences are also extremely sensitive to magnetic
      field inhomogeneities, and this sensitivity has precluded examination of regions
      of cortex near field inhomogeneities with functional MR imaging. This article
      presents a gradient-echo echo-planar imaging method that uses variable amplitude
      scaling on the slice-select refocusing lobe to generate images compensated for
      static field inhomogeneities. A technique for constructing composite images to be
      used in statistical tests for activation is also presented. The method is shown
      to produce clean activation maps in the presence of large static field
      inhomogeneities. The technique retains the sensitivity of gradient-echo imaging
      to changes in blood oxygenation while removing the sensitivity to large static
      field inhomogeneities.

PMID- 8748498
TI  - MR image-guided control of cryosurgery.
AB  - Cryoablation has recently become a useful procedure for the treatment of
      prostatic and hepatic tumors, primarily because of advances in the ability to
      monitor visually the freezing process with ultrasound. Success of the procedure
      depends in large part on how well the ice front can be positioned to destroy
      pathologic tissue, while sparing healthy tissue. This study describes a cryogen
      delivery system that can be used in conjunction with magnetic resonance (MR)
      image-guided cryoablation, and an automatic control system that uses MR image
      guidance in a feedback loop to control the ice front trajectory. Edge-detected MR
      images are used to determine the current ice front location at each time
      interval, providing feed-back to an automatic control system that adjusts the
      flow of cryogen to the cryoprobe. Numerical simulations and experimental results
      demonstrate that an ice front with cylindrical symmetry can be accurately
      controlled using this MR image-guided feedback control scheme.

PMID- 8748499
TI  - Three-dimensional triple quantum-filtered 23Na imaging of rabbit kidney with
      weighted signal averaging.
AB  - Low signal-to-noise ratio (SNR) has been the main obstacle to multiple quantum
      filtered 23Na imaging becoming an important technique for biologic and clinical
      applications. Through computer simulations and phantom experiments, we show that
      the SNR in 23Na imaging can be substantially improved by weighted signal
      averaging. Three-dimensional single quantum and triple quantum (TQ)-filtered 23Na
      images of an externalized rabbit kidney were collected with this technique. The
      TQ-filtered image did not show any signal when the animal was alive. However,
      upon sacrificing the animal, the renal cortex became clearly visible without any
      significant increase in signal from the medullary region. This increase in TQ
      filtered signal in the renal cortex may be caused by an increased concentration
      of intracellular Na+ in the large intracellular space present herein, compared
      with the medulla. To our knowledge, this study represents the first example of
      three-dimensional TQ-filtered 23Na image of a biological sample.

PMID- 8748500
TI  - Fat suppression at 7T using a surface coil: application of an adiabatic half
      passage chemical shift selective radiofrequency pulse.
AB  - The selective suppression of fat using chemical shift selective (CHESS) sinc,
      gaussian presaturation, or binomial radiofrequency pulses are widely implemented
      techniques in magnetic resonance imaging. For applications wherein transmitter
      coils that generate inhomogeneous magnetic (B1), fields are used (e.g., surface
      coils), adiabatic radiofrequency pulses that are less susceptible to spatial
      variations in B1 amplitude will improve the spatial homogeneity of spin
      excitation angle. Herein, we describe the application of an adiabatic half
      passage hyperbolic secant CHESS pulse suitable for acquiring fat-suppressed
      magnetic resonance images with surface coils on high-field systems. Images
      obtained from a water/fat phantom and from the abdominal region of a rat are
      presented indicating excellent suppression of fat signal from the entire coil
      sensitive volume.

PMID- 8748501
TI  - Radiofrequency shielding of surface coils at 4.0 T.
AB  - Because radiation loss associated with a radiofrequency (RF) coil increases as
      roughly the fourth power of the frequency, this loss mechanism may become
      important in high-field studies above 2.0 T. In this study, the contribution of
      radiation losses at 4.0 T were determined in a rectangular surface coil using an
      RF shield to modify the radiation losses. The effect of this shield was
      determined on coil Q, B1 distribution, and signal to noise as a function of
      distance between the coil and the shield. Phantoms and human tissue were
      evaluated to characterize the loss mechanisms. The results demonstrate a large
      radiation loss in the unshielded surface coil. However, the radiation losses in
      vivo were not dominant owing to a large inductive loss occurring from dielectric
      currents in the body at 170 MHz.

PMID- 8748502
TI  - MR demonstration of a cystic pheochromocytoma.
AB  - Cystic pheochromocytoma is a rare tumor of the adrenal gland that can pose a
      diagnostic challenge. We report a case of a 14-year-old boy who had an adrenal
      lesion that appeared cystic by both sonography and CT, but that demonstrated
      hemorrhage into the lesion at MR imaging, and proved to be a cystic
      pheochromocytoma. We emphasize the importance of considering the diagnosis of
      pheochromocytoma when faced with a cystic lesion of the adrenal gland.

PMID- 8748503
TI  - Giant cell tumor of the tendon sheath in the ankle: MRI with pathologic
      correlation.
AB  - We report a case of Giant cell tumor of the tendon sheath involving the ankle,
      wherein spin-echo (T1- and T2-weighted), gradient-echo, and dynamic contrast
      enhanced sequences were performed, and the tumor was noted to be very vascular.
      To the best of our knowledge, the use of gradient-echo sequences and the pattern
      of enhancement by time-intensity curves has not been reported earlier.

PMID- 8748504
TI  - Screening adolescents for metallic foreign bodies before MR procedures.
AB  - The report describes a case in which routine prescreening procedures were found
      to be inadequate for an adolescent patient referred for MR imaging.
      Recommendations are provided to correct this potential problem.

PMID- 8748505
TI  - Magnetization transfer on in vitro circulating blood: implications for time-of
      flight MR angiography.
AB  - Effects of magnetization transfer were evaluated in vitro on circulating blood.
      Various velocities were tested from 0 to 72 cm/second. Decrease signal intensity
      caused by magnetization transfer effects was inversely proportional to inflow
      velocity. It reached 10% at very low velocities and disappeared at velocities
      higher than 30 cm/second.

PMID- 8748506
TI  - Influence of the presence of chicks on the ability to resume incubation behavior
      in domestic hens (Gallus domesticus).
AB  - In this study, hormonal and behavioral changes associated with nest deprivation
      in the absence or in the presence of chicks (replaced every day or not) were
      investigated in incubating hens. Prolactin levels decreased, whereas LH and E2
      levels increased following nest deprivation. Surprisingly, the presence of chicks
      had no effect on prolactin changes. However, the presence of chicks significantly
      limited increases in plasma LH and estradiol. Furthermore, this inhibitory effect
      was greater when day-old chicks were replaced every day. On the other hand, the
      presence of chicks induced the emergence of specific maternal behavior, while,
      surprisingly, one-third of the nest-deprived hens without chicks continued to
      incubate. After a 3-day deprivation period, readiness to renest was maintained
      for a percentage of hens. Thus more than 2/3 of hens deprived of the nest for 3
      days in the presence of chicks returned to their nests during the first day of
      being allowed to do so, versus less than 1/3 of hens without chicks among those
      that previously disrupted incubation behavior. Plasma prolactin concentrations of
      these renesting hens increased rapidly and reached again levels characteristic of
      incubating hens. We conclude that, under our experimental conditions, presence of
      chicks maintains readiness to incubate without maintaining high levels of plasma
      prolactin.

PMID- 8748507
TI  - Seasonal and acute changes in adrenocortical responsiveness in an arctic-breeding
      bird.
AB  - The Lapland longspur, Calcarius lapponicus, times its breeding season so that
      chicks hatch coincident with the brief period of food abundance in the high
      arctic. This synchronization requires that all reproductive activities occur in
      over a much shorter period than at lower latitudes. Because of the known
      influence of stress hormones on delaying breeding in temperate-zone birds and the
      detrimental effects of such delays in the arctic, we expected the performance of
      the hypothalamic-pituitary-adrenal (HPA) axis of arctic-breeding birds to show
      less sensitivity to environmental stress than their mid-latitude counterparts. We
      found that adrenocortical responsiveness to the standardized stress of capture
      and handling, measured by taking five serial blood samples for corticosterone
      during the course of a 1-hr period, was similar to many temperate passerines and
      was also similar both between male and female longspurs and between the migratory
      and reproductive phases. However, the profile of plasma corticosterone during
      capture stress was significantly damped in longspurs sampled as they began their
      postnuptial molt. In addition, we had the opportunity to examine endocrine
      responses to a natural environmental stress in 1989 during a 3-day snowstorm
      which concealed available food resources. During this storm longspurs formed
      progressively larger flocks each day, with females abandoning incubation duties
      by the third day. Birds captured during the storm showed highly significant
      increases in both the rate of plasma corticosterone increase during capture and
      the peak postcapture level compared with birds sampled before the storm. This
      increased adrenal potential suggests increased activity of the HPA axis in
      response to severe conditions and is reminiscent of the response to fasting.
      Although the storm occurred during incubation, and reproductive hormone levels
      had begun to decline, we measured significant reductions in luteinizing hormone
      in both males and a subset of females captured during the storm.

PMID- 8748508
TI  - Effect of hormonal manipulation on sociosexual behavior in adult female leopard
      geckos (Eublepharis macularius), a species with temperature-dependent sex
      determination.
AB  - Aggressive and sexual behavior in the adult leopard gecko (Eublepharis
      macularius), a species with temperature-dependent sex determination (TSD), is
      influenced by the temperature experienced as an egg, as well as by prenatal and
      perinatal hormones. This study focused on the effects of hormonal manipulation of
      adult female leopard geckos from different incubation temperatures. Following
      ovariectomy, females from both all-female (26 degrees C) and male-biased (32.5
      degrees C) incubation temperatures exhibited a significant decrease in high
      posture (HP) aggression toward male and female stimulus animals. Testosterone
      treatment attenuated this decrease in HP aggression toward female but not toward
      male stimulus animals. Ovariectomy also resulted in a loss in attractiveness in
      both groups of females. Following treatment with testosterone, over 50% of the
      females were attacked by male stimulus animals, suggesting a change in the
      pheromonal cues normally secreted by females. Unmanipulated females never exhibit
      tail vibrations, a male-typical courtship behavior. However, following
      ovariectomy with testosterone treatment, half of the females from both incubation
      temperatures exhibited this behavior, indicating an activational effect of
      testosterone. An effect of incubation temperature on aggression was evident with
      females from the male-biased incubation temperature exhibiting a greater
      likelihood of aggression compared to females from the all-female incubation
      temperature. This effect continued to be detected after hormone manipulation.
      Ovariectomized females from the all-female incubation temperature were less
      aggressive even with testosterone treatment toward males, whereas females from
      the male-biased incubation temperature showed no significant decline in
      aggression following testosterone treatment, suggesting that individuals from
      different incubation temperatures may have different sensitivities to hormones.

PMID- 8748509
TI  - Hormonal responses of male gerbils to stimuli from their mate and pups.
AB  - Following copulation and cohabitation with a pregnant female, male gerbils show
      high levels of parental behavior toward their pups. The initiation of male
      parental behavior may be the result of neuroendocrine changes induced by
      cohabiting with the pregnant female or by pup stimuli. Experiment 1 examines the
      changes in androgen and prolactin levels in male gerbils cohabiting with females
      over the reproductive cycle. Gerbils were mated and blood samples taken from
      males for hormone analysis 1, 10, and 20 days after pairing and 3, 10, and 20
      days after pups were born. A group of unmated male gerbils served as controls.
      Plasma prolactin levels of males were elevated throughout the female's pregnancy
      and lactation periods, but were only statistically significantly higher than
      those of unmated males 20 days after pups were born. Androgen levels rose during
      pregnancy and dropped significantly after the birth of the pups. These hormonal
      changes are similar to those found in males of monogamous birds and differ from
      those found in males of polygynous rodents such as the rat. Experiment 2 examined
      the hormonal responses of male and female gerbils to pup replacement after 4 hr
      of parent-pup separation. Female gerbils showed a significant elevation of
      prolactin levels 1 hr after pup replacement, but males did not. Males with pups
      returned showed no difference in androgen levels from males who did not have pups
      returned. Thus, male gerbils show neuroendocrine changes following long-term
      cohabitation with their mate and pups, but do not show acute hormone responses to
      pup removal and replacement. These results indicate that parental males have
      neuroendocrine changes associated with parental behavior and these differ from
      the neuroendocrine changes underlying female parental behavior.

PMID- 8748510
TI  - Maternal aggression in rats: effects of olfactory bulbectomy, ZnSO4-induced
      anosmia, and vomeronasal organ removal.
AB  - Previous studies from our laboratory indicate that somatosensory inputs to the
      snout and ventral trunk, but not visual or auditory stimuli, play critical roles
      in the elicitation and maintenance of maternal aggression by lactating Norway
      rats toward a strange male intruder. There are conflicting reports on the
      influence of olfaction on maternal aggression. We explored the possible roles of
      central or peripheral anosmia on maternal aggression in Long-Evans rats during
      early lactation. In Experiment 1, responsiveness to both volatile and non
      volatile odors was eliminated by bilateral olfactory bulbectomy (BOB), carried
      out during mid-gestation. BOB resulted in a reduced likelihood and intensity of
      maternal aggression on days 1 and 5 of lactation (L1 and L5), but also severe
      deficiencies in maternal behavior and litter growth and survival. In Experiment
      2, anosmia to volatile odors was induced by spraying zinc sulfate intranasally on
      gestation day 21 and L1. This treatment had little or no effect on maternal
      aggression on L1 or L2 or on maternal behavior, especially if there was a 1-day
      recovery between the second treatment and testing. In Experiment 3,
      responsiveness to non-volatile odors was eliminated by vomeronasal-organ removal
      (VNX) carried out prior to mating. VNX did not disturb maternal behavior on L2-L8
      or maternal aggression on L1 or L5. These results and others suggest that the
      expression of maternal aggression is affected by volatile odors, mediated
      possibly by accessory chemosensory systems such as the septal organ, or by neural
      changes that follow olfactory deafferentation, or both.

PMID- 8748511
TI  - Progesterone-facilitated lordosis in medial preoptic area-lesioned, juvenile
      guinea pigs.
AB  - Juvenile female guinea pigs rarely display lordosis in response to estradiol and
      progesterone treatments that elicit sexual receptivity in adults. To test the
      hypothesis that the medial preoptic area (MPOA) tonically inhibits the display of
      steroid-induced lordosis in juveniles, 11-day-old guinea pigs were ovariectomized
      (OVX) and received bilateral, sham, or electrolytic lesions aimed at the MPOA 3-4
      days later. At 20-22 days of age, these females were tested for the expression of
      sexual receptivity following injections of estradiol benzoate (EB, 10 micrograms
      s.c.) and progesterone (0.5 mg s.c., 40 h after EB). The lesions damaged portions
      of the MPOA, the nucleus of the diagonal band of Broca, the lateral aspect of the
      medial preoptic nucleus, the medial part of the preventricular portion of the
      periventricular nucleus, and the anterior commissure. The lesions did not alter
      the display of estradiol-induced lordosis. However, after treatment with EB plus
      progesterone, 20% of the sham-lesioned females displayed lordosis, as compared to
      80% of the MPOA-lesioned animals. These data are consistent with the hypothesis
      that neurons originating in and/or traversing the MPOA tonically suppress the
      display of progesterone-facilitated lordosis in juvenile guinea pigs. Removal of
      this inhibitory input allows prepubertal females to respond behaviorally to
      estradiol and progesterone in an adult-typical fashion.

PMID- 8748512
TI  - An investigation into sexual motivation and behavior in female Goeldi's monkey
      (Callimico goeldii): effect of ovarian state, mate familiarity and mate choice.
AB  - Four adult female Callimico were studied in terms of their sexual motivation
      relative to three unrelated adult males using an operant paradigm followed by a
      pair test or a two-male choice test. Reductions in urinary cortisol
      concentrations and the duration of immobility were used as indicators of
      subjects' adjustment to the experimental situation. When females were tested with
      unfamiliar males there was no effect of ovarian state on operant or species
      typical measures of female sexual motivation. When females were retested with the
      same males after a 1-week familiarization, sexual motivation was higher during
      the peri-ovulatory phase than during the post-ovulatory phase in terms of operant
      but not in terms of species-typical proceptive behavior or in terms of receptive
      behavior. During the familiarization periods, female sociopositive behavior and
      sexual motivation demonstrated marked variation depending on the identity of the
      male. Males with which females demonstrated high sexual motivation during
      familiarization were the object of equal amounts of female operant behavior
      during pair tests and two-male choice tests; males with which females had
      demonstrated low sexual motivation were the objects of less female sexual
      motivation under conditions of female choice than in pair tests.

PMID- 8748513
TI  - Arginine vasotocin injection increases probability of calling in cricket frogs,
      but causes call changes characteristic of less aggressive males.
AB  - Male cricket frogs, Acris crepitans communicate to males and females using
      advertisement calls, which are arranged into call groups. Calls at the middle and
      end, but not beginning of the call group, are modified in response to male-male
      aggressive interactions. We found in this field study of male cricket frogs in
      natural breeding choruses that the peptide hormone arginine vasotocin (AVT) not
      only increased the probability that males called after injections, but also
      caused modifications in middle and end calls to produce calls characteristic of
      less aggressive males. Moreover, AVT-injected males showed significantly greater
      increases in call dominant frequency than saline-injected males, again, a
      characteristic of less aggressive males. Cricket frog calls are used to both
      repel males and attract females, thus call changes may relate to male-male and/or
      male-female interactions. Saline-injected males also demonstrated significant
      changes in several call traits, including changes that occurred in the beginning
      and middle calls of the call groups, but not the end calls. AVT appeared to block
      some call changes produced through handling. These data suggest that AVT can
      influence acoustic communication in frogs in several ways, including effects on
      call characteristics and dominant frequency, as well as potentially blocking some
      handling effects.

PMID- 8748514
TI  - The role of the uterus and cervix in systemic oxytocin-PGE2 facilitated lordosis
      behavior.
AB  - The effect of ovariectomy, hysterectomy, and cerviectomy on systemic oxytocin
      PGE2 induced facilitation of lordosis behavior was examined in estrogen and
      progesterone treated rats. Females were injected with 0.25 micrograms estradiol
      benzoate for 3 days, followed by 500 micrograms progesterone on day 4, 4 hr prior
      to behavioral testing. Ten minutes before behavioral testing with a male, females
      were injected systemically with either oxytocin (2.1, 4.2, or 8.4 micrograms);
      PGE2 (0.05, 0.10, or 0.20 micrograms); concomitant administration of both
      oxytocin and PGE2; or physiological saline. Oxytocin (2.1 micrograms) or PGE2
      (0.05 micrograms) significantly increased lordosis behavior in ovariectomized
      females; however, neither had any facilitatory effect in hysterectomized animals.
      Facilitated lordosis behavior was only reinstated in hysterectomized females that
      received concomitant administration of 2.1 micrograms oxytocin plus 0.05
      micrograms PGE2. This latter dose also resulted in a further potentiation of
      lordosis behavior in ovariectomized animals, compared to 2.1 micrograms oxytocin
      or 0.05 micrograms PGE2 alone. Concomitant administration of oxytocin and PGE2 at
      all doses had no facilitatory effect on lordosis behavior in cerviectomized
      animals. These results suggest that the uterus and the cervix may be important
      components of a peripheral mechanism by which systemic oxytocin and/or PGE2
      induce facilitated lordosis behavior in female rats.

PMID- 8748515
TI  - Stressors, including social conflict, decrease plasma prolactin in male golden
      hamsters.
AB  - Following exposure to a stressor, plasma prolactin (PRL) rises in most species.
      The purpose of the present study was to examine the effect of social conflict or
      of footshock stress on PRL responsiveness in male Syrian hamsters. Contrary to
      expectations, PRL was significantly lower in subordinate hamsters than in their
      dominant opponents or in controls following one, five, or nine exposures to
      social conflict. Similarly, PRL was reduced in hamsters subjected to a mild
      footshock stressor. By contrast, adrenocorticotropin, another stress-responsive
      hormone, was elevated following exposure to each of these stressors. We also
      demonstrate that PRL release is inhibited by dopamine as it is in other species
      by showing that there is a dose-dependent increase in PRL release following
      treatment with the dopamine receptor blocker, domperidone.

PMID- 8748516
TI  - Testosterone and aggression in male red jungle fowl.
AB  - We investigated the relationship between aggression, plasma testosterone level
      (T), and change in T in captive male red jungle fowl (Gallus gallus). T measured
      on day 1 of our experiment was positively correlated with T on day 8, suggesting
      that T remains constant in males when the social environment is stable. During
      aggressive encounters that escalated to include physical combat, males that
      attacked first (won) had increased T relative to their opponent. Males did not
      differ in T measured 1 week before the aggressive encounter. Our data suggest
      that an increase in T during aggression is associated with winning in escalated
      fights.

PMID- 8748517
TI  - A new load application system for in vitro study of ligamentous injuries to the
      human knee joint.
AB  - This paper describes the design and accuracy evaluation of a new six degree of
      freedom load application system for in vitro testing of the human knee joint.
      External loads of both polarity in all six degrees of freedom can be applied
      either individually or in any combination while the knee is permitted to move
      unconstrained in response to applied loads. The flexion/extension degree of
      freedom permits the full physiological range of motion. In addition to external
      loads, forces of the three major muscle groups (quadriceps, hamstrings,
      gastrocnemius) crossing the joint can be developed. Full automation and rapid
      convergence of loads to programmed values are achieved through a computer which
      feeds command signals to servo controller/electro-pneumatic servo values. The
      servo values regulate pressure to pneumatic actuators which develop the various
      loads. Experiments undertaken to quantify the accuracy of both load and
      displacement measurements reveal that errors particularly in load measurement are
      effectively controlled through the apparatus design.

PMID- 8748518
TI  - A six-degree-of-freedom test system for the study of joint mechanics and ligament
      forces.
AB  - A joint testing system was designed to transmit a specified motion or force to a
      joint in all six degrees of freedom (d.o.f.) using a spatial linkage system for
      position feedback. The precise reproducibility of position provided by this
      method of position feedback allows determination of in situ ligament forces for
      external joint loadings. Load on the structure of interest is calculated from six
      d.o.f. load cell output after the loaded position is reproduced with all other
      structures removed. In a test of this system, measured loads showed good
      agreement with applied loads.

PMID- 8748519
TI  - Confined compression of canine annulus fibrosus under chemical and mechanical
      loading.
AB  - Uniaxial confined compression and swelling experiments on cylindrical specimens
      taken either in an axial or in a radial direction from a canine lumbar annulus
      fibrosus are presented. The loading protocol consisted of a combination of
      stepwise mechanical and chemical loading. Swelling and consolidation curves of
      normalized displacement versus square root of normalized time did not show a
      dependence on site or orientation of the specimen. All stages in which height
      increases, namely, conditioning, swelling, and desolidation show only slight
      differences in these normalized curves. Consolidation is initially faster, and
      later slower. The transport coefficient for axial specimens is higher than for
      radial specimens, for consolidation e.g., 3.14 +/- 1.56 10(-10) m2s(-1) and 1.11
      +/- 0.33 10(-10) m2s(-1) respectively, the biphasic aggregate moduli are 1.01 +/-
      0.31 MPa and 0.66 +/- 0.30 MPa, respectively.

PMID- 8748520
TI  - Physical response of collagen gels to tensile strain.
AB  - Extra cellular matrix, which provides physical support to epithelial and
      endothelial cells and to fibroblasts, also affects a number of important cell
      biological phenomena, such as cell motility and angiogenesis. Although type I
      collagen has long been recognized as the primary structural component of the
      extra cellular matrix, little is known about the physical properties of collagen
      gels. In this study, we used a servo-controlled linear actuator to impose quick
      stretches on dilute collagen gels. An axial strain imposed on the gel within few
      milliseconds resulted in a rapid development of gel tension in the direction of
      the strain. The gel tension then decayed toward a steady-state value within
      several seconds. The instantaneous gel stiffness increased and the relaxed gel
      stiffness decreased with the extent of gel stretching. These rheological
      parameters were also dependent on the density of the collagen network. Taken
      together the results indicated that collagen gels possess nonlinear viscoelastic
      properties.

PMID- 8748521
TI  - Mechanical responses of the rabbit patello-femoral joint to blunt impact.
AB  - Various studies suggest impact trauma may initially soften cartilage, damage
      subchondral bone, or a combination thereof. The initial damages are commonly
      thought due to excessive contact pressure generated on cartilage and the
      underlying bone. The objective of this research was to develop a small animal
      model for studying post-traumatic OA and to correlate contact pressure with
      tissue damage. Blunt insult was graded by dropping a rigid mass onto the
      hyperflexed hind limb of rabbits. Contact pressure in the patello-femoral joint
      was measured with pressure sensitive film. One, 3, 6, and 14 days later the
      animals were euthanized. Damage to cartilage and the underlying bone was assessed
      visually and in microscopic sections. Indentation experiments were performed on
      the patellar cartilage with a rigid, flat probe. Contact pressures were
      nonuniform over the articular surfaces and a high frequency of surface fissures
      were generated on the lateral facet in severe insults. The appearance of surface
      fissures correlated better with the magnitude of contact pressure gradients in
      the damage zone than the magnitude of contact pressures on the facet, per se.
      Blunt trauma causing surface fissures resulted in a measurable degree of
      softening in the patellar cartilage, especially close to the defects. Surgical
      intervention of the joint to insert pressure sensitive film, however, also
      resulted in significant softening of the cartilage.

PMID- 8748522
TI  - Energy-shunting hip padding system attenuates femoral impact force in a simulated
      fall.
AB  - Recent studies suggest that hip padding systems reduce the incidence of hip
      fractures during falls. However, no data exist on the force attenuating capacity
      of hip pads under realistic fall impact conditions, and thus it is difficult to
      compare the protective merit of various pad designs. Our goal is to design a
      comfortable hip padding system which reduces femoral impact force in a fall below
      the mean force required to fracture the elderly cadaveric femur. In pursuit of
      this objective, we designed and constructed a hip pad testing system consisting
      of an impact pendulum and surrogate human pelvis. We then developed a hip pad
      containing a shear-thickening material which allows for shunting of the impact
      energy away from the femur and into the surrounding soft tissue. Finally, we
      conducted experiments to assess whether the surrogate pelvis accurately
      represents the impact behavior of the human female pelvis in a fall, and to
      determine whether our energy-shunting pad attenuates femoral impact force in a
      fall more effectively than seven available padding systems. We found the
      surrogate pelvis accurately represented the human female pelvis in regional
      variation in soft tissue stiffness, total effective stiffness and damping, and
      impact force attenuation provided by trochanteric soft tissues. We also found
      that our padding system attenuated femoral impact force by 65 percent, thereby
      providing two times the force attenuation of the next best system. Moreover, the
      energy-shunting pad was the only system capable of lowering femoral impact force
      well below the mean force required to fracture the elderly femur in a fall
      loading configuration. These results suggest that the force attenuating potential
      of hip pads which focus on shunting energy away from the femur is superior to
      those which rely on absorbing energy in the pad material. While these in-vitro
      results are encouraging, carefully designed prospective clinical trials will be
      necessary to determine the efficacy of these approaches to hip fracture
      prevention.

PMID- 8748523
TI  - Hindered transport of macromolecules through a single row of cylinders:
      application to glomerular filtration.
AB  - The slit diaphragms of renal glomerular capillaries form an ultrafiltration
      barrier which may be approximated as a row of cylindrical fibers of
      macromolecular dimensions. To describe the hindered transport of plasma proteins
      and other macromolecules through this barrier, we developed an approximate
      hydrodynamic model for spherical, Brownian particles passing through a row of
      infinitely long cylinders. The selectivity of the slit diaphragm was assessed by
      computing concentration profiles for a wide range of molecular sizes for Pe < or
      = 1, where Pe is a Peclet number based on the cylinder radius. The sieving
      coefficient for the slit diaphragm was computed as theta SD = CB/CO, where CO was
      the average concentration at a specified distance upstream from the cylinders
      (corresponding to the location of the basement membrane), and CB was the
      concentration far downstream (corresponding to Bowman's space). The results of
      previous experimental sieving studies using rats could be accounted for
      approximately by postulating a wide distribution of spacings between the fibers
      of the slit diaphragm. Comparing the results for theta SD with calculations for a
      model of the glomerular basement membrane suggests that the slit diaphragm is by
      far the more size-restrictive part of the overall barrier.

PMID- 8748524
TI  - Hemodynamics of the Fontan connection: an in-vitro study.
AB  - The Fontan operation is one in which the right heart is bypassed leaving the left
      ventricle to drive the blood through both the capillaries and the lungs, making
      it important to design an operation which is hemodynamically efficient. The
      object here was to relate the pressure in Fontan connections to its geometry with
      the aim of increasing the hemodynamically efficiency. From CT or magnetic
      resonance images, glass models were made of realistic atrio-pulmonary (AP) and
      cavo-pulmonary (CP) connections in which the right atrium and/or ventricle are
      bypassed. The glass models were connected to a steady flow loop and flow
      visualization, pressure and 3 component LDA measurements made. In the AP model
      the large atrium and curvature of the conduit created swirling patterns, the
      magnitude of which was similar to the axial velocity. This led to an inefficient
      flow and a subsequent large pressure loss (780 Pa). In contrast, the CP
      connection with a small intra-atrial chamber had reduced swirling and a
      significantly smaller pressure loss (400 Pa at 8 l.min) and was therefore a more
      efficient connection. There were, however, still pressure losses and it was found
      that these occurred where there was a large bending of the flow, such as from the
      superior vena cava to the MPA and from the MPA to the right pulmonary artery.

PMID- 8748525
TI  - Numerical simulation of airflow in the human nasal cavity.
AB  - An anatomically correct finite element mesh of the right human nasal cavity was
      constructed from CAT scans of a healthy adult nose. The steady-state Navier
      Stokes and continuity equations were solved numerically to determine the laminar
      airflow patterns in the nasal cavity at quiet breathing flow rates. In the main
      nasal passages, the highest inspiratory air speed occurred along the nasal floor
      (below the inferior turbinate), and a second lower peak occurred in the middle of
      the airway (between the inferior and middle turbinates and the septum). Nearly 30
      percent of the inspired volumetric flow passed below the inferior turbinate and
      about 10 percent passed through the olfactory airway. Secondary flows were
      induced by curvature and rapid changes in cross-sectional area of the airways,
      but the secondary velocities were small in comparison with the axial velocity
      through most of the main nasal passages. The flow patterns changed very little as
      total half-nasal flow rate varied between resting breathing rates of 125 m/s and
      200 ml/s. During expiration, the peaks in velocity were smaller than inspiration,
      and the flow was more uniform in the turbinate region. Inspiratory streamline
      patterns in the model were determined by introducing neutrally buoyant point
      particles at various locations on the external naris plane, and tracking their
      path based on the computed flow field. Only the stream from the ventral tip of
      the naris reached the olfactory airway. The numerically computed velocity field
      was compared with the experimentally measured velocity field in a large scale
      (20x) physical model, which was built by scaling up from the same CAT scans. The
      numerical results showed good agreement with the experimental measurements at
      different locations in the airways, and confirmed that at resting breathing flow
      rates, airflow through the nasal cavity is laminar.

PMID- 8748526
TI  - Separation surfaces for laminar flow in branching tubes--effect of Reynolds
      number and geometry.
AB  - Flow visualization experiments of Newtonian laminar flow through branching tubes
      have been performed to identify the shape of the separation surface or flow
      divider. The influences of Reynolds number, flow fraction into the side branch,
      and branch geometry on the separation surface shape have been considered. The
      shapes presented in this paper are formed by the intersection of the separation
      surface with the cross section of the parent tube. At low Re the separation
      surfaces are curved in a convex manner, bulging away from the opening of the side
      branch. Increasing Re causes the surface to become concave. At Re > 194 the
      surfaces can become closed for Q* > 0.3. The branch angle has no noticeable
      effect on the separation surface shape. The side to parent branch diameter ratio,
      Db/Dp, has a strong influence at low Re. As Re increases the diameter effect
      diminishes. Previous studies have shown no difference between the separation
      surfaces of T and Y type junctions at low Re. At Re = 194 there is a marked
      difference between the separation surfaces of T and Y bifurcations.

PMID- 8748527
TI  - Peristaltic pumping in a circular tube in the presence of an eccentric catheter.
AB  - The influence of an eccentrically inserted catheter on the peristaltic pumping in
      a tube is investigated under long wavelength, low Reynolds number assumptions.
      The radially asymmetric deformation of the wall arising through an eccentrically
      inserted catheter is taken into consideration by choosing an appropriate bipolar
      coordinate system. The effect of the position and size of the catheter on pumping
      characteristics is studied. The best performance of pumping is noticed at a
      certain position of the catheter. The size of the catheter, when placed
      eccentrically, alters the pressure signature significantly inside the bolus,
      unlike the concentric case discussed by Lykoudis and Roos (1971). Further, the
      maximum pressure rise in one period of the peristaltic wave is observed to
      decrease with an increase in the eccentricity.

PMID- 8748528
TI  - Variations in rupture site and surface strains at failure in the maturing rabbit
      medial collateral ligament.
AB  - The relationship between the pattern of surface strain and the site of failure in
      maturing rabbit ligaments was studied in vitro. Bone-medial collateral ligament
      (MCL)-bone complexes of 24 female New Zealand White rabbits at 3, 6, 9 and 12
      months of age (n = 6 rabbits, 12 MCLs per group) were tested in tension to
      failure. A video dimension analysis (VDA) system was used to map the surface
      strain at failure across the width and along the length of the medial side of
      each MCL during testing. Results showed that the highest strains were
      consistently located at the femoral insertion decreasing towards the
      midsubstance, with the highest strain occurring in the anterior portion of the
      MCL immediately adjacent to the femoral insertion. Strains of the complex at
      failure increased with rabbit maturation. The strain distribution however, did
      not change dramatically, even though the locations of MCL failure changed from
      exclusively tibial avulsion in the three month old rabbits to predominantly
      midsubstance failures in the 12 month old rabbits. In the six month old rabbits,
      there was a particular dissociation with all MCLs failing near the tibial
      insertion while femoral strains were apparently the highest. These results
      suggest two possibilities beyond that of some unknown artifacts of optical strain
      measurement. First, since failure sites rarely correlated with areas of maximum
      surface strain in this study, it seems possible that higher strains could exist
      deeper in the tissue, particularly at the bone-ligament interface of the tibial
      insertion in immature animals and somewhere within the midsubstance of the MCL in
      the adult. Secondly, it is possible that the ligament material may be
      heterogeneous.

PMID- 8748529
TI  - Analysis of thermal injury process based on enzyme deactivation mechanisms.
AB  - Based upon the analysis of enzyme-catalyzed reactions occurring in living tissue,
      a model of thermal injury process is presented in which the fraction of denatured
      enzyme protein was taken as the indicator of thermal damage degrees. The results
      from this model describe the dependence of thermal damage on exposure time and
      temperature elevation.

PMID- 8748530
TI  - Energy comparison between trot, bound, and gallop using a simple model.
AB  - In this paper, the dynamics of quadruped trot, gallop, and bound will be examined
      using a simple model for the quadruped. The body of the quadruped is modeled as a
      uniform bar and the legs are modeled by massless springs. It will be shown that
      symmetry can be used to study the locomotion of this system. Using symmetry, a
      technique will be developed to obtain periodic solutions for each of the gaits of
      the quadruped model. These periodic solutions will be computed at various speeds.
      The energy levels will be compared for each of the gaits. The exchange of energy
      between its different forms will be shown for different gaits. It will be shown
      that even without body flexibility, there are significant savings in energy due
      to gait transition from trot to gallop. The energy levels will be used to predict
      the trot-gallop transition speed. These results will be compared with the
      experimental results for horses and dogs.

PMID- 8748531
TI  - Cervical vertebral strain measurements under axial and eccentric loading.
AB  - The mid to lower cervical spine is a common site for compression related injury.
      In the present study, we determined the patterns of localized strain distribution
      in the anterior aspect of the vertebral body and in the lateral masses of lower
      cervical three-segment units. Miniature strain gages were mounted to human
      cadaveric vertebrae. Each preparation was line-loaded using a knife-edge oriented
      in the coronal plane that was moved incrementally from anterior to posterior to
      induce compression-flexion or compression-extension loading. Uniform compressive
      loading and failure runs were also conducted. Failure tests indicated strain
      shifting to "restabilize" the preparation after failure of a component. Under
      these various compressive loading vectors, the location which resulted in the
      least amount of deformation for a given force application (i.e., stiffest axis)
      was quantified to be in the region between 0.5- 1.0 cm anterior to the posterior
      longitudinal ligament. The location in which line-loading produced no rotation
      (i.e., balance point) was in this region; it was also close to where the
      vertebral body strains change from compressive to tensile. Strain values from
      line loading in this region produced similar strains as recorded under uniform
      compressive loading, and this was also the region of minimum strain. The region
      of minimum strain was also more pronounced under higher magnitudes of loading,
      suggesting that as the maximum load carrying capacity is reached the stiffest
      axis becomes more well defined.

PMID- 8748532
TI  - Tennis racket shock mitigation experiments.
AB  - Measured in this study was the effectiveness of two types of retrofits in
      mitigating shocks in tennis rackets with ideally high grip fixity. The retrofits
      were a cushioned grip tape and a string implant device. Three types of rackets
      were investigated: wood, graphite composite, and metal. For low speed ball
      impact, neither retrofit changed significantly the magnitude and distribution of
      e, the coefficient of restitution on the racket heads. For moderate ball speeds
      impacting the rackets along the vertical centerline, three dynamic racket
      responses were measured: the free vibration damping based on racket head
      acceleration, the root-mean-square (rms) grip reaction force, and the fast
      Fourier transform (FFT) of the grip force. These latter experiments showed that
      the string implant device had a negligible effect on the three dynamic measures
      of racket response. However, the cushioned grip tape increased racket damping by
      up to 100 percent, reduced the rms grip force by about 20 percent, and reduced
      the magnitude of the FFT of this force by about 40 percent.

PMID- 8748533
TI  - An analytical model to study blunt impact response of the rabbit P-F joint.
AB  - While mechanisms of post-traumatic osteoarthrosis are largely unknown, excessive
      stresses and strains generated in articular cartilage and the underlying bone may
      play a role. In this manuscript a technique is described for studying the impact
      response of a diarthrodial joint. A mathematical model of the rabbit PF joint
      indicated that contact pressures predicted by a quasi-static plane strain linear
      elastic model compared well with experimental data when Poisson's ratio and
      Young's modulus of the cartilage were 0.49 and 2 MPa, respectively. This value
      for the elastic modulus compared well with that obtained from elastic analysis of
      short-time indentation experiments on cartilage from a previous study. The model
      analysis also suggested that surface fissuring of patellar cartilage occurs near
      areas where shear stresses and tensile strains are high. Impact location on the
      patella significantly influenced the distributions of shear stress along the bone
      cartilage interface and tensile strains in the cartilage. These results may help
      explain some of the mechanisms of initial tissue damage reported elsewhere.
      Limited experimental data are presented here but the value of such mathematical
      models for estimation of material properties and for analysis of damage creation
      is clearly demonstrated.

PMID- 8748534
TI  - Reexamination of steady solutions of a collapsible channel conveying fluid.
AB  - The objective of this note is to reexamine the static behavior of a 2-D channel
      conveying fluid, when the wall tension becomes small or zero at some point along
      the channel. In addition to the shear stress exerted by the fluid flow, we take
      into account restoring forces acting on the wall, such as the bending moment, the
      transverse shearing force, etc., which have often been neglected in the equation
      of equilibrium of the tube wall. Numerical results show that zero wall tension
      does not mean nonexistence of steady solutions. When the wall tension becomes
      small, it is important to derive the equation of equilibrium by taking into
      account those terms which have been neglected in comparison with strong effect of
      the wall tension in physiological vessels.

PMID- 8748535
TI  - A technique for calibrating measurements from photographs of sliced specimens.
AB  - Determining the geometry of articular joint surfaces is critical to the study of
      human joint mechanics. Photographs of sliced specimens (PSS) is currently one of
      the most popular methods used to determine surface geometry. This study sought to
      improve the photographs of sliced specimens method through a new calibration
      technique that includes a mathematical model and a precise plastic grating
      (calibration grid). Simulations showed that calibration results for x and y
      coordinates using the new technique attained a high degree of accuracy that was
      independent of camera and projector lens quality, degree of parallelity between
      the projector and digitizing table and selection of the area to be calibrated.

PMID- 8748536
TI  - The serological response to Salmonella serovars typhimurium and infantis in
      experimentally infected pigs. The time course followed with an indirect anti-LPS
      ELISA and bacteriological examinations.
AB  - A total of 43 pigs, inoculated with Salmonella typhimurium (O:1,4,5,12) and un
      inoculated controls were followed weekly by blood and faecal samplings for up to
      18 weeks post inoculation (p.i.). Three pigs, inoculated with S. infantis (O:6,7)
      were followed similarly for 9 weeks. All inoculated pigs, except one, were
      positive for Salmonella by traditional faecal culture on at least one occasion
      during the first week of infection, whereafter shedding of bacteria rapidly
      declined to < 10% of the pigs from week 7. All control pigs remained Salmonella
      negative by culture of faecal samples. When examined serologically in an indirect
      ELISA using mixed purified LPS from S. typhimurium and S. choleraesuis (O:6,7),
      all but one S. typhimurium infected pig and all S. infantis infected pigs
      produced significantly increased optical densities (OD) in the ELISA as compared
      to the control groups. The maximum anti-LPS response was observed at day 22, when
      86% of the S. typhimurium inoculated pigs had seroconverted, while the frequency
      of seropositive pigs peaked at days 30 (92%) and 37 p.i. (92%). Large variations
      were found among pigs concerning time of seroconversion (between 6 and 37 days
      p.i.), maximum OD-level attained (between 8 and 130% of a reference serum) and
      persistence of reaction. At the time of necropsy, 18 weeks p.i., 67% of the S.
      typhimurium inoculated pigs were found seropositive, while 100% of the S.
      infantis inoculated pigs were found seropositive at necropsy, 9 weeks p.i.
      Salmonella in internal organs were detected at necropsy in 4/22 of the S.
      typhimurium inoculated pigs with persistent anti-LPS reaction and all 3 S.
      infantis inoculated pigs but in none of the antibody-negative pigs. The ELISA is
      therefore suitable for screening for the presence of infection with S.
      typhimurium or S. infantis on a herd basis. Its suitability for other serotypes
      of Salmonella will require further testing.

PMID- 8748537
TI  - Susceptibility to Actinobacillus pleuropneumoniae infection in pigs from an
      endemically infected herd is related to the presence of toxin-neutralizing
      antibodies.
AB  - Our objective was to identify pigs of an endemically infected herd that were
      susceptible to pleuropneumonia due to Actinobacillus pleuropneumoniae. The
      presence of toxin-neutralizing antibodies was studied in serum of 36 pigs from
      birth until 24 weeks of age. Titers gradually declined during the first twelve
      weeks of life and increased thereafter. Sera from one-hundred 3-weeks-old piglets
      and one-hundred 20-weeks-old pigs were sampled and neutralization titers were
      determined. From each group we selected 5 pigs with the lowest titers and 5 pigs
      with the highest titers. These selected pigs (n = 20) were inoculated
      endobronchially with A. pleuropneumoniae. Pigs that survived from infection were
      necropsied after 48 h. Pigs with low neutralization titers had severe lung
      lesions, whereas pigs with high titers had no or minor lung lesion. These
      differences were significant (P < 0.05). From this field study we conclude that
      susceptibility to Actinobacillus pleuropneumoniae can be predicted by absence of
      toxin-neutralizing antibodies.

PMID- 8748538
TI  - Aerobactin production by enterotoxigenic Escherichia coli of porcine intestine.
AB  - Of 135 strains of Escherichia coli from the intestines of healthy and diseased
      piglets screened, 16 (12%) were positive in a bioassay for aerobactin production.
      Of these, 15 also carried genetic determinants for heat stable or heat labile
      enterotoxins.

PMID- 8748539
TI  - The prevalence of F107 fimbriae and their association with Shiga-like toxin II in
      Escherichia coli strains from weaned Australian pigs.
AB  - A total of 480 haemolytic Escherichia coli (HEC) strains from weaned pigs were
      tested using an oligonucleotide probe to determine the prevalence of F107
      fimbriae in Australia. Of these, 62% were positive. F107 was detected in
      serogroups O141, O138, O8, O45, O139, O157 and O98 but not in O149 nor O147. 81%
      of E. coli strains not producing other fimbriae (K88, 987P, K99 or F41) were
      positive for F107; 5% of strains with K88 fimbriae also had F107. Serological
      investigation of the expression of F107 fimbriae indicated that serogroups O141,
      O138, O8, O45 and O157 produced variant F107ac. Variant F107ab was found on O139
      strains only. The F107 fimbrial subunits of both variants had a molecular weight
      of approximately 16 kDa. A total of 350 of the HEC strains were tested to
      determine the prevalence of the Shiga-like toxin II (SLT II) gene. 29.0% of these
      strains were positive. SLT II was detected in serogroups O141, O138, O149, O98,
      O45, O8 and O157 but not in O139. 25% of these strains were positive for both
      F107 and SLT II.

PMID- 8748540
TI  - Chlamydia psittaci in turkeys: pathogenesis of infections in avian serovars A, B
      and D.
AB  - At 7 days of age, 4 groups, each of twenty specific pathogen free turkeys kept in
      isolation units were inoculated by aerosol with the Texas Turkey strain (avian
      Chlamydia psittaci serovar D), strain 92/1293 (avian Chlamydia psittaci serovar
      D), strain 84/55 (avian Chlamydia psittaci serovar A) or strain 89/1326 (avian
      Chlamydia psittaci serovar B). A fifth group of 4 specific pathogen free turkeys
      were sham inoculated controls. At daily intervals for 10 days and then twice
      weekly up to 34 days post infection, one bird in each group was killed and the
      target tissues and cells for replication and the sequence of events of serovar A,
      B and D infections was examined. In these turkeys, the primary site of
      replication was the respiratory tract. Chlamydial replication could be detected
      in the respiratory tract on day 1 post inoculation (p.i.) for group A, on day 3
      p.i. for group B and on day 1 to 2 p.i. for groups D1 and D2. Subsequently, there
      was chlamydaemia and localisation in the digestive tract, in one or more
      parenchymatous organs, in the pericardium and in the conjunctivae. Specific
      immunoperoxidase staining revealed chamydiae in these organs in epithelial cells
      and in monomorphonuclear cells in all infected groups. The monomorphonuclear
      cells were identified as macrophages by double immunofluorescence staining.
      Chlamydiae were present in the same tissues for serovars A and D, but could not
      be demonstrated in proventriculus, duodenum, pancreas, ovaries and testes for
      serovar B. Furthermore, the intensity of replication was similar for all
      serovars. However, for serovar B in comparison with the other serovars, the
      bacteria appeared in most tissues 1 to 6 days later and the maximal replication
      in these tissues occurred 3 to 4 days later.

PMID- 8748541
TI  - Serological crossreactivity between Brucella abortus and Yersinia enterocolitica
      0:9 I immunoblot analysis of the antibody response to Brucella protein antigens
      in bovine brucellosis.
AB  - Sera from three groups of Brucella abortus infected cattle were examined in
      immunoblots with the following antigens: sodium dodecyl sulfate/mercapto ethanol
      (SDS/ME) extracts of two rought B. abortus strains (45/20 and RB51) and rough B.
      ovis, smooth lipopolysaccharides (SLPS) from B. abortus strain 99 and Y.
      enterocolitica 0:9, and a cytoplasmic extract from smooth B. abortus strain 19-S.
      The sera groups were: (1) 26 sera from animals, experimentally infected with B.
      abortus strain 544, which were all positive in the conventional brucellosis
      serological tests; (2) 152 sera from naturally infected cattle herds with varying
      titres in the conventional brucellosis tests, and (3) 30 sera from naturally
      infected cattle with varying titres in the conventional brucellosis tests and
      from which B. abortus was cultured. B. abortus strain 99 and Y. enterocolitica
      serotype 0:9 SLPS staining showed up frequently in all sera groups and correlated
      well with the strength in the conventional brucellosis tests, confirming the
      immunodominance of SLPS in B. abortus infections. Another immunodominant
      component of 50-80 kDa was found in the rough B. abortus 45/20 antigen
      preparation but not in the B. abortus RB51 and in the B. ovis cell extracts. This
      component was also recognised by sera from Y. enterocolitica 0:9 infected cattle
      and is probably a protein-lipopolysaccharide complex. Although many of the sera
      from B. abortus infected cattle with high titres in the conventional brucellosis
      tests showed complex protein staining patterns in blots, no protein bands other
      than the 50-80 kDa bands were found to be immunodominant.

PMID- 8748542
TI  - Serological crossreactivity between Brucella abortus and Yersinia enterocolitica
      0:9 II the use of Yersinia outer proteins for the specific detection of Yersinia
      enterocolitica infections in ruminants.
AB  - Yersinia outer protein (YOP) preparations from Y. enterocolitica and Y.
      pseudotuberculosis were used as antigens in immunoblots for the detection of
      Yersinia infections in experimentally and naturally infected ruminants. Sera from
      9 groups of animals were used: (1) 51 sera from cattle which were false-positive
      in the standard brucellosis serological tests, (2) 52 sera from brucellosis
      negative cattle, (3) 51 sera from a deer herd in which 16 animals were positive
      in the brucellosis tests and Yersina species were isolated from 5 animals, (4) 50
      sera from a deer herd in which sera from all animals were negative in the
      brucellosis tests, (5) 107 sera from brucellosis-negative cattle which were
      received from throughout New Zealand, (6) 30 sera from cattle naturally infected
      with B. abortus and from which B. abortus was isolated, (7) 55 sera from cattle
      naturally infected with B. abortus, (8) 26 sera from cattle experimentally
      infected with B. abortus, with mostly high titres in the conventional brucellosis
      tests, and (9) sera taken weekly from 3 cattle experimentally infected with Y.
      enterocolitica 0:9. In all 3 Y. enterocolitica 0:9 experimentally infected
      animals the antibody reactivity against major YOPs in the Y. enterocolitica and
      in the Y. pseudotuberculosis YOP preparation correlated well with the strength in
      the classical brucellosis tests and with the staining of smooth
      lipopolysaccharides (SLPS) in blots, thus confirming the usefulness of YOPs for
      the detection of Yersinia infections. Sera from naturally infected cattle and
      deer herds, regardless of whether they were false positive or negative in the
      brucellosis tests, showed high frequencies of staining in YOP blots (53-58% in
      cattle and 80-100% in deer), indicating a high prevalence of field infections
      with Yersinia species in New Zealand. In two of the three sera groups from B.
      abortus infected animals, antibodies against YOPs were detected with high
      frequency, showing that dual infections may be common and may interfere with
      differential serological testing.

PMID- 8748543
TI  - Phenotypic characterisation of Pasteurella multocida isolates from Australian
      poultry.
AB  - A phenotypic characterisation of 110 isolates of bacteria previously identified
      as Pasteurella multocida was performed. Reference strains of many of the
      currently recognised species within the genus Pasteurella were included in the
      study. All the isolates had been obtained from Australian poultry-67 from
      chickens, 42 from turkeys and one from a duck. Ten different biochemical biovars
      were recognised amongst the isolates. Four of these biovars, representing 91
      isolates, were identified as P. multocida subsp. multocida. One biovar,
      consisting of one isolate, was identified as P. multocida subsp. septica and
      another biovar, consisting of five isolates, as P. multocida subsp. gallicida.
      Two further biovars were tentatively identified as ornithine decarboxylase
      negative P. multocida subsp. multocida (five isolates) and maltose positive P.
      multocida subsp. septica (one isolate). The final two biovars, consisting of five
      and two isolates each, could not be assigned to any of the currently recognised
      subspecies of P. multocida.

PMID- 8748544
TI  - Influence of chondroitinase on indirect hemagglutination titers and phagocytosis
      of Pasteurella multocida serogroups A, D and F.
AB  - Capsules of Pasteurella multocida serogroups A, D and F contain
      mucopolysaccharides which block antigenic determinants and prevent phagocytosis.
      In this study, capsules of serogroup A, D and F strains of P. multocida were
      depolymerized by enzyme treatment. Capsule depolymerization of serogroup D and F
      strains with chondroitinase increased indirect hemagglutination (IHA) test titers
      and enhanced phagocytosis by swine neutrophils. Capsule depolymerization of
      serogroup A strains with hyaluronidase increased IHA titers, but depolymerization
      with chondroitinase did not. When serogroup A strains were treated with a
      combination of chondroitinase and hyaluronidase, IHA test titers were lower than
      titers of the same strains treated with hyaluronidase alone. Combined enzyme
      treatment of serogroup D strains resulted in IHA test titers similar to those of
      chondroitinase treatment alone.

PMID- 8748545
TI  - Antimicrobial activity of chicken and turkey heterophil peptides CHP1, CHP2,
      THP1, and THP3.
AB  - Four avian heterophil antimicrobial cationic peptides (Chicken Heterophil
      Peptides 1 and 2, and Turkey Heterophil Peptides 1 and 3) were evaluated for in
      vitro microbicidal activity against selected avian pathogens and human pathogens
      which are harbored by birds. At concentrations of 16-2 micrograms/ml, all four
      avian peptides effected a greater than 90% reduction in the survival of Candida
      albicans, Salmonella enteriditis, and Campylobacter jejuni. None of the peptides,
      including the known antimicrobial peptide protamine (used as a positive control),
      were able to reduce the survival of Pasteurella multocida by 90% at the maximum
      peptide concentration (16 micrograms/ml) tested. At 16 micrograms/ml, the turkey
      peptide THP3 did not effect a 90% reduction in survival of Bordetella avium,
      Escherichia coli, or Salmonella typhimurium, while all of the other peptides
      tested were effective at this concentration or less. This peptide, THP3, does not
      share the same homologous amino acid sequence shared by the other three peptides.
      Under our experimental conditions, none of the peptides neutralized Infectious
      Bronchitis Virus, an enveloped coronavirus of chickens.

PMID- 8748546
TI  - Molecular epidemiology of Mycoplasma mycoides subsp. mycoides biotype Small
      Colony, the agent of contagious bovine pleuropneumonia.
AB  - Restriction endonuclease analysis (REA) and immunoblotting were used to compare
      field strains of Mycoplasma mycoides subsp. mycoides biotype Small Colony from
      different parts of Europe and Africa. Of the 27 strains tested by REA, the
      European ones (n = 15), except 3 from the Iberian peninsula, differed strikingly
      from the African ones (n = 10). Vaccinal strains T1-SR and KH3J had a unique REA
      pattern. Polyclonal immunoblot profiles of 46 strains appeared fairly similar.
      However most of the Italian strains (22 out of 24) shared a characteristic, in
      the 100 kDa area, unlike that of the other European strains. Immunoprofiles of
      the reference strain PG1 and vaccinal strain T1-SR were different from the
      others. These results allowed the determination of possible links between
      different geographic region of enzootic contagious bovine pleuropneumonia.

PMID- 8748547
TI  - Six antigenic groups within the genus pestivirus as identified by cross
      neutralization assays.
AB  - Antigenic differences between pestivirus isolates of ruminant and porcine origin
      were characterized by neutralization assays. First, six different clusters of
      pestiviruses were identified by clustering cross-neutralization results of 13
      pestivirus strains tested against 23 sera. Cluster I consisted of four strains of
      bovine viral diarrhoea virus (BVDV) of bovine origin and two BVDV isolates of
      porcine origin. Cluster II consisted of one sheep isolate and two porcine BDV
      isolates. Cluster III consisted of one classical swine fever virus strain and
      cluster IV, V, and VI each consisted of one strain isolated from a giraffe, a
      deer, and a pig. After the clusters were identified, one-way neutralization tests
      were used to test a total of 45 pestivirus isolates. Although the same six groups
      were found, results of some individual strains differed from previous cross
      neutralization results and the results obtained by typing with monoclonal
      antibodies. The discrepancy between one way neutralization tests and cross
      neutralisation tests is demonstrated clearly by recalculation of the cross
      neutralization results without the classical swine fever sera. We conclude that
      neutralization tests are only suitable to characterize antigenic differences when
      virus strains are tested in a cross-neutralization test.

PMID- 8748548
TI  - Development of a simple, rapid and accurate in vitro whole blood technique for
      the detection and semi-quantification of FIV cellular viremia.
AB  - A new, simple, rapid and accurate culture technique is described for a semi
      quantitative analysis of cellular viremia in FIV-infected cats. This assay can be
      carried out with small amounts of whole blood, and is based on the detection of
      FIV core gag antigen, which is released in culture supernatants. The amount of
      core antigen produced is measured with an enzyme-linked immunoassay using
      specific monoclonal antibodies. This whole blood technique (WB method) was
      compared with a culture method using isolated peripheral blood mononuclear cells
      (PBMC method). FIV could be detected in whole blood of all experimentally
      infected cats, but not from uninfected cats. This assay offers a number of
      advantages (small blood samples required, no leukocyte separation and lymphocyte
      purification procedures) and its reproducibility is very good. It provides a
      convenient in vitro cellular assay for viral semi-quantitation, well adapted for
      monitoring efficacy of prototype FIV vaccines or experimental antiviral drugs.
      Also, it could facilitate the study of the pathogenesis of FIV-related
      progressive immunodepression. Finally, it offers an alternative to serological
      techniques for diagnostic purposes in several circumstances: early viremia,
      maternal antibodies.

PMID- 8748549
TI  - Spirochetes isolated from dairy cattle with papillomatous digital dermatitis and
      interdigital dermatitis.
AB  - Two groups of spirochetes were isolated from papillomatous digital dermatitis
      (PDD) lesions in dairy cattle. The two groups could be readily differentiated on
      the basis of morphologic and immunologic characteristics and enzymatic activity.
      A spirochete isolated from an interdigital dermatitis (IDD) lesion appeared
      morphologically and antigenically similar to spirochetes in one of the PDD groups
      and exhibited an identical enzyme activity pattern. The two groups of PDD
      spirochetes had characteristics most consistent with the genus Treponema. The PDD
      and IDD isolates differed morphologically from previously described bovine
      Treponema spp. Although spirochetes have been observed to be one of the
      predominant bacterial morphotypes in PDD and IDD and are found invading the
      stratum spinosum and dermal papillae in PDD lesions, the significance of these
      spirochetes in the etiopathogenesis of PDD and IDD is presently unknown.

PMID- 8748550
TI  - Apoptosis in chicken embryo fibroblasts caused by Newcastle disease virus.
AB  - The GB strain of Newcastle disease virus (NDV) was used to infect chicken embryo
      fibroblasts (CEF). At various times after infection, CEF were harvested and
      processed for DNA extraction, flow cytometry and electron microscopy. Agarose gel
      electrophoresis of the DNA at 12 h after infection, showed a laddering pattern,
      indicating fragmentation of cellular DNA. Flow cytometry analysis of the infected
      cells showed an increase in the population of smaller cells (apoptotic cells).
      Electron microscopic examination showed extensive cellular necrosis, but also
      showed some other cells with condensed chromatin and with extensive perinuclear
      fragmentation of chromatin; apoptotic bodies could also be readily seen. These
      data suggest that NDV infection of CEF causes apoptosis, in addition to necrosis.

PMID- 8748551
TI  - Differentiation of African horse sickness viruses by polymerase chain reaction
      and segments 10 restriction patterns.
AB  - This paper describes a single tube reverse transcription-polymerase chain
      reaction (RT-PCR) method for detection of African horse sickness virus (AHSV).
      The genomic segments 10 of viruses of the 9 AHSV serotypes were amplified. The
      758bp products were digested to completion by restriction enzymes. The
      restriction fragment length polymorphisms of segments 7 and 10 cDNA allowed the
      differentiation of the nine serotypes.

PMID- 8748552
TI  - Diagnosis of fetal infection with porcine parvovirus by in situ hybridization.
AB  - In situ hybridization (ISH) for the diagnosis of fetal infection with porcine
      parvovirus (PPV) was compared with immune electron microscopy (IEM) and serology
      by immunofluorescence (IF) for its sensitivity and its applicability in a routine
      diagnostic laboratory. The technique was applied to the examination of sections
      of formalin-fixed paraffin-embedded tissues from 68 fetuses. Fifty-three of these
      fetuses were diagnosed serologically since they had a crown rump length of more
      than 17 cm, i.e. they were mature enough to mount a humoral immune response; 38
      were positive and 15 negative. Eleven out of 15 smaller fetuses examined for the
      presence of viral antigen by immune electron microscopy (IEM) were positive and 4
      were negative. Heart and lung were found to be the most suitable organs for in
      situ hybridization. In situ hybridization yielded a positive result in 8 of the
      11 IEM positive fetuses and in 33 of the 38 serologically positive fetuses. No
      signal was detected in any of the 4 IEM or the 13 serologically negative fetuses.
      Expenses for IEM were estimated to be 179% of the expenses for ISH. Expenses for
      serology by IF on the other hand were 67% of the expenses for ISH. From this it
      was concluded that the most efficient way to diagnose a fetal infection with PPV
      was serology by IF, if possible with samples from several fetuses and that the
      other techniques, IEM or ISH, ought to be reserved for those cases where no
      immunocompetent fetuses were available for diagnosis.

PMID- 8748553
TI  - Detection of ileal symbiont intracellularis in porcine faecal samples by
      polymerase chain reaction.
AB  - Ileal Symbiont Intracellularis (ISI), the organism causing proliferative
      enteritis (PE) in pigs was detected in faeces by the application of polymerase
      chain reaction (PCR). The assay based on a 319 base pair DNA fragment was used on
      faecal and mucosal samples derived from pigs either affected or unaffected with
      PE. As few as 10(3) ISI could be detected in pig faeces spiked with ISI. No
      amplification product was detected in the faeces of unaffected pigs but faeces of
      confirmed clinical cases were positive. This method offers an accurate,
      sensitive, easy to perform alternative to monoclonal antibody tests or
      histological examination post-mortem for the presence of ISI in pig herds.

PMID- 8748554
TI  - Cytocidal infection of hog cholera virus in porcine bone marrow stroma cell
      cultures.
AB  - Porcine bone marrow stroma cell (BMSC) cultures producing cells of granulocyte
      lineage were established. Hog cholera (HC) virus ALD and Alfort strains
      replicated in the porcine BMSC cultures showing distinct cytopathic effect (CPE).
      The differentiation of granulocyte-lineage cells in the cultures ceased after
      infection with HC virus. Polyclonal antibody against the ALD strain inhibited
      completely the development of CPE of the both ALD and Alfort strains. Monoclonal
      antibodies (mAbs) specific to the ALD strain inhibited CPE of the ALD strain,
      while CPE of the Alfort strain was not affected by those mAbs, suggesting that
      CPE induced in the BMSC cultures is due to HC virus.

PMID- 8748555
TI  - Incidental asymptomatic orbital calcifications.
AB  - OBJECTIVE: To use modern computed tomography (CT) imaging to quantify the
      incidence of asymptomatic incidental orbital calcifications and describe their
      histological features. MATERIALS AND METHODS: One hundred orbital CT scans were
      reviewed. In addition, patients who had orbital calcification(s) detected on a
      brain CT scan were examined by the ophthalmology service. RESULTS: Of the orbital
      CT scans, 2% had bilateral drusen of the optic nerve head, 3% had calcified
      scleral plaques anterior to the medial or lateral rectus muscles, and 3% had
      bilateral ossification of the trochlear apparatus. Routine brain CT scans
      detected asymptomatic calcifications of the sclera and dura surrounding the
      proximal optic nerves. CONCLUSION: Incidental asymptomatic orbital calcifications
      are commonly encountered on modern high-resolution CT images of the brain and
      orbit. This article should help the clinician to confidently distinguish these
      densities from foreign bodies or pathological calcifications.

PMID- 8748556
TI  - Recovery from ocular ischemic syndrome after treatment with verapamil.
AB  - Vasospasm has been implicated as a cause of amaurosis fugax, which can be
      controlled by administration of the calcium channel blockers nifedipine or
      verapamil. However, vasospasm has not previously been thought to be involved in
      chronic ocular ischemia. We report a patient with ocular ischemic syndrome, which
      may have had vasospasm as a contributing cause, since the patient also developed
      amaurosis fugax despite daily aspirin therapy. An 80-year-old man with chronic
      open-angle glaucoma developed chronic ocular ischemia characterized by
      progressively decreased visual acuity, pain, rubeosis, and hypotony, as well as
      transient visual dimming. Medical evaluation revealed no evidence of carotid
      stenosis, thromboembolism, or vasculitis as the cause of ocular ischemia. When
      the calcium channel blocker verapamil was administered, the episodes of transient
      visual dimming ceased immediately. In addition, soon thereafter, visual acuity
      improved, the rubeosis partially regressed, and the hypotony reversed. This case
      indicates that the calcium channel blocker verapamil may be effective in treating
      cases of ocular ischemic syndrome, when vasospasm is a contributing cause.

PMID- 8748557
TI  - Rapid growth of an intracranial aneurysm causing apparent retrobulbar optic
      neuritis.
AB  - We describe a 31-year-old man who developed sudden painful loss of vision in the
      right eye and was found to have a retrobulbar optic neuropathy. Magnetic
      resonance (MR) imaging gave normal results, and a diagnosis of retrobulbar optic
      neuritis was made. The patient was treated with oral prednisone, but he continued
      to lose vision in the right eye and then began to lose vision in the left eye.
      Repeat MR imaging performed eight weeks after the initial study showed a giant
      intracranial aneurysm compressing the right and left optic nerves. Cerebral
      angiography revealed that the aneurysm arose from the origin of the right
      ophthalmic artery. Treatment of the aneurysm by a trapping procedure resulted in
      improvement in vision in the left eye but no change in vision in the right eye.
      This report emphasizes the difficulty in imaging intracranial aneurysms of
      various sizes, the rapidity with which intracranial aneurysms can enlarge, and
      the importance of continued follow-up examinations in patients thought to have
      idiopathic optic neuritis.

PMID- 8748558
TI  - Simultaneous, multiple cranial neuropathies in diabetes mellitus.
AB  - Cranial mononeuropathies, particularly ophthalmoplegia and facial palsy, are
      common entities in the diabetic population. Simultaneous multiple cranial
      neuropathies due to diabetes are much less common, however. We present three
      patients with this entity.

PMID- 8748559
TI  - Cavernous sinus hemangioma. Clinical and neuroimaging features.
AB  - A patient presented with an isolated left sixth nerve palsy. Magnetic resonance
      imaging revealed a sharply marginated 3 cm lesion in the left cavernous sinus,
      which was isointense to gray matter on T1-weighted images, hyperintense on T2
      weighted images, and enhanced with paramagnetic contrast material. Cerebral
      angiography showed a homogeneous blush fed by an enlarged meningohypophyseal
      artery. The neuroimaging findings were thought to be most consistent with the
      diagnosis of a cavernous sinus meningioma. At the time of surgery, a vascular
      mass was encountered, and a biopsy was consistent with a cavernous hemangioma.
      This report describes the clinical and neuroimaging features of cavernous sinus
      hemangiomas that may help to differentiate them from other cavernous sinus
      lesions.

PMID- 8748560
TI  - Vertical gaze paralysis and intermittent unresponsiveness in a patient with a
      thalamomesencephalic stroke.
AB  - A patient with paralysis of upward gaze and downward gaze, absent oculocephalic
      reflexes, and absent vertical saccades also demonstrated intermittent stupor over
      the first 9 days of presentation. Magnetic resonance imaging (MRI) demonstrated
      an infarct in the tegmentum of the mesencephalon including the right red nucleus
      and the periaqueductal area, superior to the oculomotor nucleus, and contiguous
      through the left thalamus. The infarct included the area around the rostral
      interstitial nucleus of the medial longitudinal fasciculus (riMLF), as well as
      the midbrain reticular formation. Mechanisms are proposed for the unusual
      concurrent sign of intermittent unresponsiveness in this case.

PMID- 8748561
TI  - Lid nystagmus as a sign of intrinsic midbrain disease.
AB  - A 6-year-old boy with signs and symptoms of ocular myasthenia gravis had lid
      nystagmus evoked by horizontal gaze. MR imaging demonstrated an intrinsic
      midbrain lesion, which was diagnosed by biopsy as a low-grade astrocytoma. In the
      setting of ocular myasthenia gravis, the finding of lid nystagmus may serve as a
      useful clinical sign of intrinsic midbrain disease.

PMID- 8748562
TI  - Neuro-ophthalmology and systemic disease--Part II. An annual review (1994).

PMID- 8748563
TI  - Optic neuritis treatment trial.

PMID- 8748564
TI  - Hashing out a policy on conflicts of interest for a P&T committee.

PMID- 8748565
TI  - New hemodialysis membranes and vancomycin clearance.

PMID- 8748566
TI  - Nefazodone: a new antidepressant.
AB  - The chemistry, pharmacology, pharmacokinetics, and clinical efficacy of
      nefazodone hydrochloride, a new antidepressant, are described. Nefazodone
      enhances serotonin (5-hydroxytryptamine [5-HT]) synaptic transmission by acting
      as an antagonist at 5-HT2 receptors and by inhibiting the reuptake of 5-HT. These
      two mechanisms combined may enhance 5-HT1A-mediated transmission. In addition,
      nefazodone weakly inhibits the reuptake of norepinephrine. Nefazodone is a
      structural analogue of trazodone but is pharmacologically distinct. In placebo
      controlled trials, nefazodone was as effective as imipramine for the treatment of
      major depression and produced clinical benefits in patients with depression
      related anxiety and sleep disturbances. More than 2000 patients have received
      nefazodone in clinical trials. The most commonly reported adverse drug reactions
      (ADRs) are asthenia, somnolence, dry mouth, nausea, constipation, dizziness,
      lightheadedness, confusion, abnormal vision, and blurred vision. The incidence of
      sexual-dysfunction ADRs may be less than that reported for other antidepressants.
      Nefazodone does not inhibit rapid-eye movement sleep. Nefazodone, an inhibitor of
      the hepatic P-450 isoenzyme CYP3A4, may increase concentrations of drugs
      metabolized by this isoenzyme, such as terfenadine, astemizole, triazolam,
      alprazolam, and midazolam. Caution should be exercised in administering
      nefazodone hydrochloride with triazolobenzodiazepines, and coadministration with
      terfenadine or astemizole is contra-indicated. The dosage should start at 100 mg
      twice daily and then be increased, depending on occurrence of ADRs and the
      patient's clinical response, to 300-600 mg daily. In elderly or debilitated
      patients, the initial dosage should be half the usual dosage. Nefazodone
      hydrochloride is as effective as other available antidepressants and may cause
      fewer ADRs.

PMID- 8748567
TI  - Rectally administered sodium polystyrene sulfonate.

PMID- 8748568
TI  - Adsorption and desorption of loperamide hydrochloride by activated attapulgites.

PMID- 8748569
TI  - Pharmacy's transition to a proactive practice mode.

PMID- 8748570
TI  - Conversion from oral to i.m. fluphenazine not a simple matter.

PMID- 8748571
TI  - Unsafe activities of compounding pharmacists.

PMID- 8748572
TI  - Hotline volunteer.

PMID- 8748573
TI  - Hitchcock's experimental series of foetal implants for Parkinson's disease: co
      grafting ventral mesencephalon and striatum.
AB  - Following 4 previous experimental series of foetal implants (mesencephalon) to
      treat patients with Parkinson's disease subjects (N7) in the fifth series were
      treated with co-grafts of foetal mesencephalon and striatum implanted
      stereotactically into the caudate nucleus bilaterally. The clinical outcome,
      better than in the previous series, included improvements lasting through 18
      months follow-up in activities of daily living, clinical neurological motor
      examination, timed motor tasks, and dyskinesia-with reduction in the patients'
      need for dopaminergic medication.

PMID- 8748574
TI  - Parkinsonian rigidity, dopa-induced dyskinesia and chorea--dynamic studies on the
      basal ganglia-thalamocortical motor circuit using PET scan and depth
      microrecording.
AB  - Regional cerebral glucose metabolism (rCMRGlu-18FDG) was measured in 6 cases with
      rigid type Parkinson's disease (PD) (2 cases with dopa-induced dyskinesia = DID),
      6 cases with chorea (Ch), 5 cases with essential tremor (EssT) and 2 cases with
      normal subjects (N). The effects of L-Dopa on rCMRGlu was studied in 3 cases with
      PD. With the aid of depth microrecording study, stereotactic pallidotomy was
      performed in all cases with PD. Thalamotomy was performed in 3 cases with Ch. In
      the EssT and N group, the metabolic pattern was high in the frontal cortex (FCx)
      but low in the lenticular nucleus (LN). In contrast, all cases with a rigid type
      PD showed lower rCMRGlu in FCx (premotor, prefrontal area). However, 4 out of 6
      cases were higher in LN than the control group. Administration of L-Dopa shifted
      rCMRGlu toward the normal pattern in this group. Five out of 6 cases with Ch
      represented higher rCMRGlu in FCx (3 focal, 2 diffuse) but lower in LN. Moreover,
      when DID occurred, it showed almost the same pattern as in Ch.
      Electrophysiological studies showed high background neuronal activity (BNA) in
      the medial segment of the globus pallidus (GP) but low BNA in the lateral segment
      of the GP in the rigid type of PD. In cases with Ch, irregular burst discharges
      were often encountered in ventro-oral thalamus. From these results, the on-going
      changes of basal ganglia-thalamocortical motor circuit in cases with a rigid type
      PD, DID and Ch are discussed. The underlying mechanisms of Parkinsonian rigidity
      was considered to contrast with those of DID and Ch within the same motor
      circuit.

PMID- 8748575
TI  - Anatomic and physiological considerations in pallidotomy for Parkinson's disease.
AB  - Our ongoing study of ventral pallidotomy for the control of Parkinson's disease
      in selected patients has provided the opportunity to explore the topographical
      and somatotopic organization of the human globus pallidus. Utilizing
      microelectrode techniques we have obtained recordings which were correlated with
      data from MPTP-parkinsonian primates. In addition, we performed pre- and post
      operative FDG/PET scans in these patients. Our studies reveal similarities
      between the MPTP-parkinsonian primate model and human Parkinson's disease in
      terms of physiologic recordings and responses. However, we have encountered
      significant differences between dominant and non-dominant hemisphere
      representations, particularly for the hand, in the human. In addition, our PET
      studies confirmed, as in previous parkinsonian primate models, glucose
      hypermetabolism in the lenticular area of Parkinson's disease patients. This
      hypermetabolism is dramatically altered by creation of a lesion in the globus
      pallidus medialis. This is demonstrated by follow-up PET scans which reveal not
      only a decrease in metabolism of the operated lenticular region, but also in the
      frontal cortical projections. These combined observations of the cellular
      activity in the globus pallidus and the observed changes in PET metabolism
      support the selection of the pallidum for lesioning and control of Parkinson's
      disease, and offer insight into the underlying physiology of this disorder. The
      above physiological and PET data will be clinically correlated with our ongoing
      series of 35+ patients.

PMID- 8748576
TI  - CT guided thalamotomy for movement disorders in multiple sclerosis: problems and
      paradoxes.
AB  - Unilateral ventrolateral (VL) thalamotomy for medically refractory tremorigenic
      movement disorders (MD) was performed in 9 patients with established multiple
      sclerosis. All patients had abolition of their coarse action/kinetic tremor with
      improvement in arm and hand function. In two patients some intention tremor
      either remained or was unmasked. Target coordinates ranged from 2 to -5 mm
      relative to the intercommissural line and from 8 to 16 mm lateral to the midline.
      There were no permanent surgical complications and the one stage procedure under
      local anesthetic was well tolerated. Although there were also improvements in
      posture and speech in some patients the overall and longer term functional impact
      of surgery was, except in two patients, disappointing. Since multiple sclerosis
      is a spectrum of disease entities, and tremor may be only one manifestation of
      the disease, clinical studies that use comprehensive patient assessments and
      objective criteria may allow prediction of longer term functional outcome in
      specific patient subgroups. The specific aims of the stereotactic procedure in
      severely disabled patients with MS and MD must also be clear.

PMID- 8748577
TI  - Long-term clinical, electrophysiological and urodynamic effects of chronic
      intrathecal baclofen infusion for treatment of spinal spasticity.
AB  - Seventeen patients with severe disabling spinal spasticity were selected and
      treated by chronic intrathecal baclofen infusion using an implanted programmable
      pump. Nine patients were tetraparetic, seven were paraplegic and one paraparetic.
      Patients were regularly followed for 5 to 69 months (mean 37.5 months). The
      clinical efficacy of baclofen was estimated by means of evaluation of:
      hypertonia, spasms, pain and functional disability. All patients experienced
      significant amelioration of quality of life secondary to reduction of hypertonia,
      spasms and pain related to contractures. Neurogenic pain improved in 3 cases and
      remained unchanged in 3 others. In patients whose motor functions were partially
      preserved, various degrees of motor improvement were detected.
      Electrophysiological recordings of Polysynaptic flexion reflexes (FR) were
      obtained to control conditions, and under intrathecal baclofen, in order to
      quantify the spinal excitability responsible for spontaneous or induced spasms.
      Flexion reflex threshold was increased and amplitude proved to be very
      significantly reduced by chronic baclofen infusion in all our patients. Twelve
      patients with neurogenic bladder dysfunction were also evaluated by a clinically
      oriented questionnaire and by quantitative urodynamic recordings, before and
      after pump implantation. In patients with normal micturition, this was not
      changed by intrathecal baclofen. In patients with spastic bladder, intrathecal
      baclofen produced a decrease of detrusor hypertonia and hyperactivity in 50% of
      cases, with reduction of leakage and increase in functional bladder capacity.

PMID- 8748578
TI  - A neurophysiological method for the evaluation of motor performance in spastic
      walking patients.
AB  - Intrathecal baclofen is at present the best treatment for severe spasticity of
      various etiologies. In walking patients affected by severe spasticity a careful
      evaluation of the motor performance is needed for a correct indication for this
      treatment. The examination should focus on the delicate balance between
      spasticity and voluntary muscle activation which is crucial for an improvement of
      motor performance during gait. Seven patients have been neurophysiologically
      evaluated by the use of a Cibex apparatus measuring torque and movement velocity
      of the lower limbs simultaneously with static and dynamic recordings of the EMG.

PMID- 8748579
TI  - Microelectrode monitoring of cortical and subcortical structures during
      stereotactic surgery.
AB  - We describe microelectrode recording and stimulation techniques to delineate the
      cellular boundaries and neural projections of stereotactic brain targets. These
      techniques have applications in the surgery for pain, movement disorders and in
      psychosurgery. Neuronal records from stereotactic operations including
      thalamotomy, pallidotomy, cingulotomy and anterior capsulotomy are discussed.
      These tools are used to distinguish gray matter from white matter, to obtain
      direct measures of cellular activity in the target, to identify the physiological
      properties and receptive fields of the subpopulation of neurons at the electrode
      tip and to avoid lesion making induced injury to adjacent structures.
      Microelectrode recording and stimulation techniques improve physiological
      localization and decrease the possibility of unwanted neurological complications
      with functional stereotactic procedures.

PMID- 8748580
TI  - Neurophysiological monitoring of cranial nerves during posterior fossa surgery.
AB  - Intraoperative neurophysiological monitoring of cranial nerve functions in
      surgery for microvascular decompression and tumors of the posterior fossa is
      important for minimizing risk of permanent damage to the nerves. In particular,
      intraoperative BAEP and the EMG function of muscle innervated by trigeminal and
      facial muscle have been found useful. We report here our experiences with
      intraoperative monitoring of brainstem auditory evoked potentials (BAEP) and EMG
      recorded from muscles supplied by the trigeminal and facial nerves.

PMID- 8748581
TI  - A frameless stereotaxic localisation system using MRI, CT and DSA.
AB  - The authors present a method of stereotaxic localisation using magnetic resonance
      imaging (MRI) computerized tomography (CT) and digital subtracted angiography
      (DSA) which does not require localisation frams fixed to the patient's skull, but
      uses only four cranial landmarks corresponding to the holders of the
      neurosurgical stereotaxic frame. The method presents no major constraints in
      routine examinations. The geometrical distortions of the imaging devices are
      corrected. Three-dimensional localisation is performed using sagittal and axial
      slices in MRI, axial slices in CT and only two associated frontaly and lateral
      views in DSA. The images data are transferred to a PC-based system. By locating
      the landmarks on the images, the transformation matrixes can be computed to
      obtain the 3D coordinates of a target in the stereotaxic space and in any imaging
      modality. The results obtained show the precision of the corrections and the
      millimetre accuracy of pin-point target localisation.

PMID- 8748582
TI  - 3D laser scanning for image guided stereotactic neurosurgery.
AB  - While this work is in its very early stages, the 3D laser scanner shows
      significant promise as a surgical localization device with advantages over other
      sensing methods. Accurate 3D surface extraction and matching, a central problem
      in computer vision, is the key to frameless stereotaxic neurosurgery using this
      technique.

PMID- 8748583
TI  - Frameless stereotaxy and interactive neurosurgery with the ISG viewing wand.
AB  - Preliminary experience with the ISG wand for frameless stereotaxy is presented.
      The wand is a multijointed mechanical arm with a range of 25 inch radius sphere.
      The arm has a analog/digital hybrid transducers to locate the spatial position of
      the probe tip. The real time displays of triplanar 2D images with an optional
      2D/3D image helps in surgical planning and interactive surgery. Seventeen
      patients underwent neurosurgical procedures with the help of wand. The wand was
      used to place minimal craniotomies, localise the brain-tumour interface and
      excise the lesions. The wand had an accuracy of 1.8 mm (SEM +/- 0.36 mm) in
      localising the lesions. Thus, the use of frameless stereotaxy has made easier and
      more precise surgical planning in several applications.

PMID- 8748584
TI  - The impact of interactive image guided surgery: the Bristol experience with the
      ISG/Elekta viewing Wand.
AB  - From June 1992 to August 1994 we have accumulated a 305 case experience with the
      ISG Viewing Wand, the first commercially available system for interactive image
      guided neurosurgery. Prior to the arrival of the wand 2.5% of intracranial
      procedures were carried out using the Leksell G frame for image guidance. Since
      the arrival of the wand that percentage of procedures suitable for image guidance
      has increased to 10%. The wand was used for 287 supratentorial procedures, 108
      craniotomies, 48 trephine exposures, 34 burr hole biopsies, 4 ventriculoscopies
      and 1 shunt insertion, 19 posterior fossa explorations were performed, 28 skull
      base procedures, including 22 transsphenoidal pituitary operations, 3
      petrousectomies and 3 orbital explorations were also carried out. In addition 3
      spinal cases were included in the series, 2 transoral explorations and 1 sacral
      laminectomy. The technique was applicable to 193 tumour cases, 14 vascular cases
      including 7 aneurysms and 16 epilepsy cases. Both CT (70%) and MRI (30%) scans
      were used for image guidance. Contour matching algorithms were used for
      registration throughout. Since the arrival of the wand conventional stereotaxy
      has been used for 26 cases, 22 stereotactic biopsies, 2 thalamotomies and 2
      craniotomies (0.5% of intracranial procedures). We conclude that contour
      matching, interactive image guidance using a mechanical arm has replaced frame
      based stereotaxy in our department except for point source localisation in deep
      midline structures. It is a technique that has universal application to
      intracranial neurosurgical procedures and as such represents a major advance in
      image guided neurosurgery.

PMID- 8748585
TI  - Stereotactic endoscopic interventions in cystic brain lesions.
AB  - Stereotactic endoscopic techniques are extremely helpful in diagnosis and therapy
      of cystic intracerebral space occupying lesions. Acute space occupying lesions
      can be managed effectively and without major tissue traumatization. Up to now we
      have operated on more than 70 cystic intracerebral space occupying lesions with a
      stereotactic endoscopic technique. The main diagnoses were colloid cysts, cystic
      craniopharyngeoma, arachnoidal and pineal cysts. In must be stressed that in
      cystic anaplastic astrocytomas and glioblastomas as well as metastases only an
      acute inner cerebral decompression can be achieved by neuroendoscopic techniques
      in combination with the application of reservoir systems. In benign parenchymal
      or intraventricular cysts neuroendoscopic intervention is performed for
      definitive treatment. The results are overall encouraging. There was no operative
      mortality and operative morbidity was below 3%. Postoperative follow-up in
      patients with benign cysts showed no evidence of recurrence.

PMID- 8748586
TI  - Neurosurgery for affective disorders at Atkinson Morley's Hospital 1948-1994.
AB  - Neurosurgical practice in the treatment of affective disorders has changed
      dramatically over the last 40 years. This paper traces the changes which have
      occurred in one institution, namely Atkinson Morley's Hospital, Wimbledon,
      London, UK from 1948 to the present day. Freehand operations designed by
      McKissock and performed on large numbers of patients disappeared as better non
      surgical treatments became available and long term complications and treatment
      failures became dearer. In the 1970's stereotactic limbic leucotomy, a much more
      focal and accurate operation, was devised and became popular. The present day
      practice utilises precisely the same techniques as the original stereotactic
      limbic leucotomy but is employed on small numbers of patients. The procedure
      continues to have a role for those few patients with severe psychiatric illness,
      particularly obsessive compulsive disorder, which has proved refractory to other
      therapeutic modalities.

PMID- 8748587
TI  - Frontal cingulotomy reconsidered from a WGA-HRP and c-Fos study in cat.
AB  - A recent positron emission tomography (PET) study demonstrated that the anterior
      cingulate cortex (area 24), in addition to SI and SII cortices, was activated by
      painful stimuli. In order to elucidate the participation of relay nuclei in the
      ascending pain pathway to area 24, we performed a regrograde labelling study with
      WGA-HRP injection into area 24 in cats. Area 24 was found to receive pain-related
      thalamic inputs from the intralaminar nuclei including the central medial
      nucleus, midline nuclei, modiodorsal nucleus and possibly the submedial nucleus.
      We then examined the expression of Fos protein in CNS induced by formalin
      injection into the face in cats. Fos positive neurons were demonstrated in areas
      23 and 24, the anterior limbic area, insular cortex, midline and paraventricular
      nuclei in the thalamus, paraventricular nucleus and other areas in the
      hypothalamus, and in many nuclei in the brainstem in both the formalin-injected
      group and the control group (anesthesia only). Labelled regions appeared to
      correspond to stress-related sites. The sole difference from the control group
      was the expression of Fos in the coronal gyrus and in the trigeminal caudalis
      nucleus in the experimental group. Although more Fos positive cells were observed
      in area 24 in experimental than in control cats, the difference was not
      significant. Our findings suggest that the demonstrated response of area 24 on
      PET scan represents stress- and emotion-related events rather than pain. Surgical
      intervention into the anterior cingulate cortex including cingulotomy thus
      appears to relieve stress and emotion associated with chronic pain, but not pain
      itself.

PMID- 8748588
TI  - Localisation of epileptic foci with multichannel magnetoencephalography, MEG.
AB  - With the development of multichannel magnetoencephalographs biomagnetic signals
      can be recorded over large areas at the same time. It allows determination of the
      magnetic field outside the head generated by spontaneous epileptic discharges.
      From the maxima of outward and inward magnetic fluxes the locations of the
      sources of epileptic discharges can be calculated. The biomagnetic signals
      originating from an epileptic discharge is, however, mixed with biomagnetic
      signals generated by the background activity of the brain. A localisation based
      on a single discharge will therefore be influenced by the background activity. To
      diminish this influence, the biomagnetic signals during repeated identical
      epileptic discharges have been averaged. It gives a source localisation common to
      all discharges instead of a widely spread cluster of dipole sources. The error of
      epileptic dipole source localisations varies with the site of the dipole in the
      head as judged from studies with implanted dipole sources but also with the
      direction of the dipole as seen in studies with artificial dipoles in real head
      volumes. The error is relatively small in areas where the head has a spherical
      surface if the dipole direction is tangential. At other sites or dipole
      directions, the error can be very large. Since the site and direction of an
      epileptic dipole source is unknown it is not possible to estimate the error of
      localisations except by using models of individual head volumes.

PMID- 8748589
TI  - Partial seizures with onset in central area: use of the callosal grid system for
      localization.
AB  - Focal seizures arising in the central area require precise anatomic and
      physiologic mapping of ictal onset. The central sulcus is identified by the
      callosal grid system whose mid-vertical plane identifies the central sulcus
      inferiority where the central artery passes into the central sulcus. 5 patients
      with intractable seizures of central origin where localized with this method.
      Extent of resection was confirmed on postoperative NRI. The subdural grid was
      accurately placed on the central sulcus, confirmed by electrophysiologic means.
      Grid planes compartmentalized ictal onset, and post-operative resection
      correlated precisely. All patients are seizure-free. Seizures arising in the
      central area, precisely located, can be treated with good to excellent results.
      Localization of onset is facilitated by use of the callosal grid system, and
      allows superimposition of pre-, intra- and post-operative anatomic and
      physiologic data.

PMID- 8748590
TI  - Pain--old and new methods of study and treatment.
AB  - In the last 5 years several remarkable methods for localizing precisely a wide
      range not only of specific motor and sensory functions but as well of more
      complex mental phenomena in the domain of cognitive functions have been
      demonstrated to evoke sharply localizable responses. In pain, positron emission
      tomography (PET) scanning has been used to show that the anterior gyrus cinguli
      is an integral component of the pain system. The PET technique suffers from a
      limitation of both spatial and temporal resolution, which permits only accurate
      center of mass coordinates of activated regions. Functional mapping of the brain
      by nuclear magnetic resonance has been achieved with techniques depicting
      specific brain areas in action during a mental process. These techniques open up
      an entirely new domain for study and treatment of many problems linked to
      cognition including many in whom pain is a central feature. The many cerebral
      cortical areas involved in pain make it unlikely that any ablative procedure will
      achieve long sustained pain relief. The dual objective of relief of both pain and
      suffering is probably going to be attained only by activation of pain suppressor
      mechanisms. This may well require the added knowledge accessible only by
      functional magnetic resonance imaging.

PMID- 8748591
TI  - CT-guided pain procedures for intractable pain in malignancy.
AB  - CT-guided stereotactic percutaneous destructive procedures, i.e. percutaneous
      cordotomy, trigeminal tractotomy, and extralemniscal myelotomy, have been
      routinely used for the treatment of localized intractable pain in malignancy
      since 1987. In 67 cases if local pain due to malignancy, CT guided percutaneous
      cordotomy was performed and in 97% complete pain control was achieved. In 45 of
      these cases, a "selective cordotomy" was performed meaning that analgesia was
      produced only in the painful region of the body. CT guided trigeminal tractotomy
      was applied to a total of 19 cases in 5 of which pain had been caused by
      malignancy. The results were satisfactory. 12 cases, suffering from visceral pain
      due to malignancy, were treated by CT-guided extralemniscal myelotomy and in 10
      cases pain relief was achieved.

PMID- 8748592
TI  - Electrophysiological monitoring during CT-guided percutaneous cordotomy.
AB  - During percutaneous cordotomy, impedance monitoring and electric stimulation have
      been widely used to enable a precise localization of the lesion electrode. The
      purpose of this study was to examine the possibility that the usage of additional
      electrophysiological techniques could help in improving the precision of the
      placement of the lesion electrode. Fourteen patients were monitored with 4
      different techniques during CT-guided percutaneous cordotomy: 1) Median nerve
      somatosensory evoked potentials (mSEP): median nerve stimulation with recording
      from the scalp. 2) Spinal cord evoked potentials (SCEP): median nerve stimulation
      with recording via the cordotomy electrode. 3) Spinothalamic evoked potentials
      (SthEP): stimulation via the cordotomy electrode and recording from the scalp.
      Ipsilateral and contralateral mSEPs and SCEPs did not change after the lesion.
      SthEPs showed a significant decrease in 10 of 12 patients provided the stimulus
      intensity was kept below that producing a motor response (approx 0.5-1 mA). There
      was no obvious relationship between changes of the evoked potentials and the
      clinical outcome of the cordotomy. Our results suggest that there may be a
      relationship between the extent of the lesion and the decrease of the
      spinothalamic evoked potentials.

PMID- 8748593
TI  - Transplantation of human chromaffin cells for control of intractable cancer pain.
AB  - Adrenal medullary chromaffin cells produce high levels of endogenous opioid
      peptides. Recent data suggest that transplantation injected locally into the
      spinal subarachnoid space reduced intractable malignant pain. In order to
      determine the feasibility, the efficacy and the risks of using adrenal medullary
      tissue for control of irreducible pain, we have developed a transplantation
      protocol on cancer pain patients selected when they required chronic intrathecal
      injection of morphine and progressively increasing doses to maintain the level of
      analgesic effects. At the present time, our clinical trial involves 8 patients.
      We report here our initial results (mean follow-up: 5 months). The various data
      collected before and after the intrathecal administration of chromaffin cells
      included: 1) Pain evaluation over time, with concomitant narcotic intake, 2) CSF
      sampling through an implanted access port to determine the following biological
      parameters: biochemical assay for opioid peptides, cell count and phenotyping of
      lymphocytes, 3) peripheral blood samples for lymphocyte typing. The results
      confirm the efficacy of adrenal medullary transplantation into spinal CSF for
      controlling irreducible cancer pain. Complementary intrathecal and oral morphine
      were totally stopped in 2 cases and stabilized in 5 others. It seems essential to
      have an important volume of grafted tissue to achieve analgesia with high levels
      of metenkephalin in CSF. A progressive decrease in metenkephalin release was
      observed from 2 to 4 months after the transplantation. Two patients with a long
      term follow-up (8 and 12 months) needed another intrathecal chromaffin cell
      graft.

PMID- 8748594
TI  - Severe peripheral ischemia after vasospasm may be prevented by spinal cord
      stimulation. A preliminary report of a study in a free-flap animal model.
AB  - Electric spinal cord stimulation (SCS) is at present used in many centers to
      treat ischemic pain and ischemia in peripheral vascular disease. The most
      promising results have been obtained in cases where a vasospastic component is
      dominating. The knowledge concerning the mechanisms behind these effects has been
      scanty, but recent experimental studies indicate that suppression of sympathetic
      activity and the release of vasoactive substances may be important. A problem
      with many of the animals studies aimed at exploring these mechanisms is that they
      have almost exclusively been performed on normal animals without ischemia.
      However, in studies of the responsiveness of local ischemia to various
      pharmacological substances and to electrical transcutaneous nerve stimulation,
      animal models with ischemic skin flaps have been used. We applied SCS via
      chronically implanted electrodes in a model of local vasospasm in the rat,
      induced by mechanical stimulation of the vessel supplying an island flap in the
      groin. Male Sprague-Dawley rats were used. First, a monopolar system for spinal
      cord stimulation, with the intraspinal cathode at vertebral level T11, was
      implanted in halothane anaesthesia. After about three days of recovery the rats
      were anaesthetized with chloral hydrate ip and a groin neurovascular flap based
      on the epigastric vessels was raised. Microcirculation in the flap as well as in
      a control area in the contralateral groin was monitored by laser Doppler
      technique. Vasospasm was induced by gently pinching the superficial epigastric
      artery with microforceps. Two groups of animals were submitted to two spasm
      periods, one with SCS applied for 20 min. by 50 Hz; 0.2 msec and with 2/3 of the
      intensity required for a motor response before the first period. The second
      group, receiving sham SCS, served as a control. Both degree of ischemia after
      spasm provocation and the time to recovery were evaluated. In general SCS
      affected basal flow very little. In the control group the rats demonstrated
      increasing vasospastic reactions with subsequent flap ischemia to the two
      mechanical provocations. In the experimental group a response pattern emerged
      indicating that pre-spasm SCS could both reduce the spasm amplitude and
      significantly shorten the time for restoration of a satisfactory microcirculation
      in the flap. Some few trials with pharmacologically induced spasm by topical
      application of noradrenaline onto the feeding vessel also followed the same
      pattern. In conclusion, SCS seems to be able to reduce vasospasm, especially if
      the treatment is given before the ischemic period. This approach may supply an
      animal model for further studies of possible mechanisms behind the
      microcirculatory effects of SCS.

PMID- 8748595
TI  - Spinal cord stimulation versus reoperation for failed back surgery syndrome: a
      prospective, randomized study design.
AB  - Retrospectively reported results of spinal cord stimulation compare favorably
      with those of neurosurgical treatment alternatives for the treatment of failed
      back surgery syndrome, including reoperation and ablative procedures. There has
      been no direct prospective comparison, however, between SCS and other techniques
      for pain management. Therefore, we have designed a prospective, randomized
      comparison of spinal cord stimulation and reoperation in patients with persistent
      radicular pain, with and without low back pain, after lumbosacral spine surgery.
      Patients selected for reoperation by standard criteria are randomly assigned to
      initial treatment by one or the other technique. The primary outcome measure is
      the frequency of crossover to the alternative procedure, if the results of the
      first have been unsatisfactory after 6 months. Results for the first 27 patients
      reaching the 6-month crossover point show a statistically significant (p = 0.018)
      advantage for spinal cord stimulation over reoperation. Many other potentially
      important outcome measures will now be followed long-term as a larger overall
      study population accumulates.

PMID- 8748596
TI  - Spinal cord stimulation versus spinal infusion for low back and leg pain.
AB  - The relative roles of spinal cord stimulation and the spinal infusion of opioids
      in the treatment of chronic, non-cancer lower body pain remains unclear. This
      report contains a retrospective analysis of patients with chronic lower body,
      neuropathic pain and treated over a 5 year period. Unilateral leg and/or buttock
      pain was treated initially with spinal stimulation and bilateral leg or mainly
      low back pain was treated initially with spinal infusions. 26 patients received
      spinal stimulation. Pain relief was > or = 50% in 16 (62%) with increased
      activity levels. Stimulator coverage was most difficult or failed in patients
      with buttock pain. 16 patients received long-term spinal infusions. Pain relief
      was > or = 50% in 2 (13%) but 25-49% in another 8 (50%) with stable infusion
      doses and was best in patients requiring low-dose (< 1 mg/h morphine intrathecal)
      infusions in the trial period. The review indicates that spinal infusions may be
      best for bilateral or axial pain that has not responded to spinal stimulation.
      Clonidine appears to be an alternative in high-dose morphine patients. New
      diamond-shaped electrode and dual quadripolar arrays appear to be very helpful
      for back, buttock, and/or bilateral leg pain patterns.

PMID- 8748597
TI  - Treatment of the failed back surgery syndrome due to lumbo-sacral epidural
      fibrosis.
AB  - The failed back surgery syndrome (FBSS) is a severe, long-lasting, disabling and
      relatively frequent (5-10%) complication of lumbosacral spine surgery. Wrong
      level of surgery, inadequate surgical techniques, vertebral instability,
      recurrent disc herniation, and lumbo-sacral fibrosis are the most frequent causes
      of FBSS. The results after repeated surgery on recurrent disc herniations are
      comparable to those after the first intervention, whereas repeated surgery for
      fibrosis gives only 30-35% success rate, and 15-20% of the patients report
      worsening of the symptoms. Computerized tomography (CT) with contrast medium and,
      in particular, Gd-DPTA enhanced MRI have recently allowed a differentiation
      between these two pathologies permitting us to adopt different therapies. In 1982
      92 we applied spinal cord stimulation (SCS) as a first therapy of FBSS with
      proven lumbo-sacral fibrosis. Fifty-five patients underwent percutaneous trial
      SCS with a mono/multipolar electrode placed at the level of Th9-12. In the 36
      patients who had a positive response to the trial stimulation, the electrode was
      connected to an implantable neurostimulator. On January '94 a third party, not
      involved in the treatment of the patients, controlled 34 of the 36 patients with
      a mean follow-up of 55 months. We classified the patients reporting at least 50%
      pain relief and satisfaction with result as successful, and 56% of the patients
      fell in that category. 10 out of 34 patients were able to resume their work. The
      success rate was significantly higher in females (73%) than in males, and in
      radicular rather than axial pain. Our data have led us to consider SCS as a first
      choice treatment in FBSS due to lumbo-sacral fibrosis.

PMID- 8748598
TI  - Significance of the spinal cord position in spinal cord stimulation.
AB  - The effects of the antero-posterior and medio-lateral positions of the spinal
      cord in the dural sac on the perception threshold and paresthesia coverage in
      spinal cord stimulation were analyzed. The distributions of the dorsal
      cerebrospinal fluid (CSF) layer thickness, measured from transverse MR scans of
      normal subjects at various spinal levels, were used to calculate the
      distributions of threshold voltages for the stimulation of spinal nerve fibers by
      a computer model. These theoretical threshold distributions were shown to fit
      well to the corresponding distributions of perception threshold measured in
      patients. It is concluded that the thickness of the dorsal csf layer is the main
      factor determining the perception threshold and paresthesia coverage in spinal
      cord stimulation: an increasing thickness raises the threshold and reduces the
      coverage, and vice versa. The effects of an asymmetrical electrode position with
      respect to the spinal cord midline were also analyzed by computer modeling. It is
      concluded that a lateral asymmetry of less than 1 mm gives a significant
      reduction of perception threshold and may result in unilateral paresthesiae.

PMID- 8748599
TI  - Anatomical findings in microsurgical vascular decompression for trigeminal
      neuralgia. Correlations between topography of pain and site of the neuro-vascular
      conflict.
AB  - We here report on the anatomical findings in a series of 350 patients with
      trigeminal neuralgia (TN) and operated on using a microsurgical key-hole approach
      to the CPA. In 5.7% there was a tumour or a vascular malformation, in 2.3% a mega
      vertebro-basilar-artery. Among the remaining 322 (= real idiopathic TN), only
      3.1% had no visible compressive factor, whilst 96.9% had one (or several)
      conflicting vessel(s): SCA in 90%, AICA in 23.6%, a vein in 24.7%. In 35.7% of
      the patients, several neurovascular conflicts (NVC) were found. Beside the
      NVC(s), a global atrophy of the entire root was seen in 67% of the cases. Degree
      of severity of the NVC and its site along the root were studied. The site of the
      conflict was: anteriorly to the root when pain was in V1, anteriorly and
      superiorly when in V2, superiorly and posteriorly when in V3.

PMID- 8748600
TI  - The Duke experience with the nucleus caudalis DREZ operation.
AB  - The nucleus caudalis DREZ operation has been performed in three phases at Duke.
      Between 1982 and 1988 radiofrequency (RF) lesions were made in the trigeminal
      nucleus extending from the C2 root to the obex using a straight electrode.
      Complications include ipsilateral arm ataxia due to spinocerebellar tract injury
      and ipsilateral lower limb weakness from the pyramidal tract. The former occurred
      at least transiently in 90% of cases. The electrode employed from 1988 to 1989
      had proximal insulation protecting the spinocerebellar tract. Since 1989 a ninety
      degree bend has been added to the electrode to allow better placement. Two
      electrodes are used to accommodate the shape of the caudalis nucleus. A total of
      101 procedures have been performed. The newest electrodes were used in 46
      procedures. Ataxia is recognized in 39%. Overall pain relief was excellent in 34%
      and good in 40%. In post herpetic neuralgia 71% enjoyed excellent or good relief.
      Indications include post herpetic neuralgia, deafferentation pain (anaesthesia
      dolorosa, post-tic dysesthesia, stroke, MS, gasserian tumour, Gamma Knife
      radiation injury), facial trauma/surgery, atypical facial pain, and
      migraine/cluster headache. A study to compare this operation to deep brain
      stimulation prospectively for the above indications has been initiated.

PMID- 8748601
TI  - Cortical stimulation for central neuropathic pain: 3-D surface MRI for easy
      determination of the motor cortex.
AB  - Motor cortex electric stimulation has been reported to be effective for the
      treatment of central post-stroke pain and trigeminal neuropathic pain. Five
      patients with pain due to injury of the trigeminal nerve and with abnormalities
      of facial sensibility, as well as two patients suffering of a post-stroke
      thalamic pain, were subjected to stimulation applied epidurally on the motor
      cortex. Quadripolar electrodes were implanted under local anaesthesia and the
      precise location of the motor cortex was determined on three-dimensional surface
      MRI the day prior to surgery. In our experience, correct topographic localization
      of the electrode on the motor cortex seems to be crucial to obtain pain
      reduction.

PMID- 8748602
TI  - A new approach to the control of central deafferentation pain--spinal intrathecal
      baclofen.
AB  - We investigated the short-term effects of an intrathecal bolus injection of
      baclofen on central pain due to stroke or spinal cord injury. Pain relief was
      obtained in 64% of the patients. The effects developed 1-2 hours after the
      injection and continued for 10-24 hours. Both spinal segmental and supraspinal
      mechanisms may be involved in the production of baclofen-analgesia.

PMID- 8748603
TI  - Differential diagnosis of parkinsonism.
AB  - The diagnosis of idiopathic Parkinson's disease (PD) is essentially clinical and
      is reached by exclusion. An akinetic rigid syndrome frequently means PD, although
      a number of other neurodegenerative diseases can share bradykinesia, rigidity,
      postural instability, and sometimes tremor. Parkinsonism can be classified as
      follows: degenerative, metabolic, vascular, iatrogenic, toxic, infectious,
      traumatic, and secondary to mass effect. The diagnostic approach are discussed.

PMID- 8748604
TI  - Autonomic disorders in Parkinson's disease.
AB  - Patients with idiopathic Parkinson's disease (IPD) often show signs and symptoms
      of autonomic involvement, related to the disease itself or to its progression.
      The more frequently disturbances reported are connected with loss of
      extrapyramidal motor control, i.e. dysphagia, gastric emptying and the most
      common constipation. They concern about 73% of the patients. A high frequency of
      urinary symptoms, ranging from 37% to 71%, is also reported in IPD, in particular
      detrusor hyperreflexia causing urgency, frequency of micturing or urgency
      incontinence. Another autonomic groups of symptoms are related to the failure of
      cardiopressor adaptability which involve 15% of the subjects and are more typical
      of late onset cases or forms bordering with the Multiple System Atrophy, finally
      resulting in orthostatic hypotension (OH).

PMID- 8748605
TI  - A genetic study of Parkinson's disease.
AB  - We performed a case-control study on 100 patients with Parkinson's disease, their
      spouses and the same number of sex- and age-matched neurological controls to
      clarify if family history of Parkinson's disease or essential tremor may increase
      the risk for the disease. We included in the study 68 male and 32 female
      parkinsonian patients with a mean age +/- SD of 62.0 +/- 9.9 years and a mean
      disease duration of 7.5 +/- 5.7. The odds ratio for familial Parkinson's disease
      was 13.4 (95% confidence limits = 6.5-27.7) and for familial essential tremor 3.1
      (95% confidence limits = 1.5-6.3). We also reviewed the genetic features of 122
      parkinsonian patients with at least one affected relative. The presence of
      secondary cases among both first-degree (n = 83) and less close relatives (n =
      72) suggests that sharing environmental factors does not explain the familial
      aggregation of the disease. Secondary cases were significantly more frequent in
      the paternal than in the maternal line (70 vs. 39). The presence of secondary
      cases among both siblings (46) and parents (37) and the unilateral distribution
      of ancestral secondary cases suggest an autosomal dominant inheritance with
      incomplete penetrance.

PMID- 8748606
TI  - Do cognitive changes of Parkinson's disease result from dopamine depletion?
AB  - Cognitive changes have long been observed in patients with Parkinson's disease:
      visuo-spatial deficits, memory disorders, dysexecutive syndrome. Given the
      modulatory role of the basal ganglia and related structures, these deficits might
      result from more fundamental disorders concerning the allocation of attentional
      resources, the temporal organization of behavior, the maintenance of
      representations in working memory or the self-elaboration of internal strategy,
      all of which resemble dysfunctions of processes that are commonly considered to
      be controlled by the frontal lobes. This suggests a functional continuity between
      the basal ganglia and association areas of the prefrontal cortex. The recent
      description in primates of parallel, segregated loops that interconnect well
      defined subregions of the basal ganglia to discrete areas of the prefrontal
      cortex via the thalamus may give some support to this hypothesis.

PMID- 8748607
TI  - The role of monoamine oxidase and catechol O-methyltransferase in dopaminergic
      neurotransmission.
AB  - The action of dopamine (DA) released in the synaptic cleft is mainly terminated
      by its reuptake and catabolism by the enzymes monoamine oxidase (MAO) and
      catechol O-methyltransferase (COMT). Preclinical data show that the reduction of
      the catabolism of DA elicited by MAO and COMT inhibitors leads to an enhancement
      of DA neurotransmission. Moreover, there is evidence suggesting that MAO-B
      inhibition might protect DA neurons from oxidative stress. Nevertheless, due to
      differences in enzyme localization and activity between man and rodents, results
      obtained in experimental animals might not reflect the actual situation in
      humans. Today the availability of potent and selective MAO and COMT inhibitors
      makes it feasible for the clinician to test whether the blockade of catabolic
      enzymes would result in a symptomatic improvement in Parkinsonian patients, and
      whether MAO-B inhibition might additionally exert a neuroprotective effect.

PMID- 8748608
TI  - Basic research in substantia nigra and ventral tegmental area: clinical
      implications.
AB  - In this review we will briefly examine some physiological and pharmacological
      aspects of the dopaminergic and non-dopaminergic cells of the midbrain in
      relationship to pathological conditions such as extrapyramidal disorders, mental
      illness, drug seeking behaviour and epilepsy.

PMID- 8748609
TI  - Does treatment with dopamine agonists affect utilization of exogenous levodopa in
      the parkinsonian striatum?
AB  - When the nigrostriatal projection is partially destroyed in Parkinson's disease,
      remaining neurons fire more rapidly and accelerate synthesis and release of
      dopamine (DA) from endogenous tyrosine and levodopa. It was suggested that such
      surviving hyperactive nigral neurons can also enhance the utilization of
      exogenous levodopa and generate adequate amounts of functional dopamine molecules
      to correct the reduced nigrostriatal neurotransmission. DA agonists stimulate
      presynaptic DA receptors and suppress nigrostriatal firing rates. Many
      parkinsonians are treated with a combination of DA agonists and levodopa. This
      could theoretically suppress both discharge of surviving dopaminergic neurons and
      their ability to convert exogenous levodopa to dopamine. To test this
      possibility, rats were injected i.p. with lisuride, bromocriptine or apomorphine
      alone or one hour after levodopa and decapitated one hour later. The DA agonists
      suppressed striatal DOPAC and DOPAC/DA ratios indicating attenuation of basic DA
      turnover. DA agonists given with levodopa did not decrease the levodopa-induced
      elevations in striatal levodopa, DA and DOPAC. Findings suggest that agonists do
      not affect entry of levodopa from the circulation into brain and do not alter
      striatal generation of DA from exogenous levodopa despite inhibition of
      nigrostriatal firing. Therefore, utilization of levodopa does not seem to depend
      on the state of discharge rates of nigral neurons and effect of levodopa and DA
      agonists in Parkinson's disease is additive.

PMID- 8748610
TI  - The modulation of dopamine receptors in rat striatum.
AB  - In the last decades, the contribution given by basic electrophysiology to the
      understanding of the nigrostriatal pathway in mammals has been rather important.
      The main results obtained by our group will be revised in this short review. The
      most common responses produced by dopamine (DA) on the principal striatal cells
      (the medium spiny neurons) are the modulation of the corticostriatal synaptic
      transmission and the decrease of voltage-dependent inward conductances. After
      blockade of DA transmission, both spontaneous and cortically driven glutamatergic
      postsynaptic potentials were inhibited by the selective activation of DA D2
      receptors. In naive animals, the DA-mediated inhibition of postsynaptic firing
      activity was mediated by D1 receptor activation. Nevertheless, the two main
      subclasses of DA receptors seemed to cooperate in the formation of the long-term
      depression (LTD) of excitatory synaptic transmission in the striatum. The
      excitotoxic hypothesis of neurodegeneration has further stimulated our interest
      towards the study of the interactions between DA and other neurotransmitters into
      the basal ganglia.

PMID- 8748611
TI  - On the functional significance of primate retinal dopamine receptors.
AB  - Diverse dopamine receptors have been identified in the primate retina. Evidence
      summarized from human and monkey retinal electrophysiological studies (ERG)
      suggests that separate D1 and D2 receptor activation results in stimulus
      dependent antagonistic effects. Studies were performed using Haloperidol, 1
      sulpiride, CY 208-243 and dopamine. It is inferred that the antagonistic
      functions of D1 and D2 receptors synergistically determine the inverted U-shaped
      spatial contrast response function of the primate retina. An understanding of the
      logic performed by retinal D1 and D2 receptors may be useful to discern
      properties of the role of diverse dopamine receptors in basal ganglia DA
      circuits.

PMID- 8748612
TI  - Intranigral injections of glutamate antagonists modulate dopamine D1-mediated
      turning behavior and striatal c-fos expression.
AB  - The contribution of the substantia nigra (SN) in the positive interaction between
      dopamine D1 receptor agonists and glutamate antagonists was studied in rats with
      a unilateral 6-hydroxydopamine (6-OHDA) lesion of dopaminergic nigro-striatal
      pathway. Local infusion into the SN of the 6-OHDA lesioned side of NMDA glutamate
      antagonists MK 801 and CPP or the AMPA antagonist NBQX at doses inducing none or
      minimal behavioral effects, significantly increased the turning behavior and the
      expression of c-fos induced, in the lesioned caudate-putamen (CPu), by a
      parenteral administration of SKF 38393. High doses of MK 801 or CPP infused into
      the SN produced intense contralateral turning per-se but induced only sparse c
      fos expression in the lesioned CPu. The results show that a depression of SN pars
      reticulata efferent neurons, potentiates D1-mediated responses and suggest that
      this area may play a role in the positive interaction between glutamate
      antagonists and D1 receptor agonists.

PMID- 8748613
TI  - Dopamine mediated responses in 6-hydroxydopamine lesioned rats involve changes of
      the signal transduction.
AB  - A single dose of the D1 agonist SKF 38393 (3 mg/kg) produces contralateral
      turning in unilaterally 6-hydroxydopamine lesioned rats only after a previous
      exposure of the animals to a dopamine agonist. This priming phenomenon is here
      investigated by studying the phosphorylation of DARPP-32, a dopamine- and cyclic
      AMP-regulated phosphoprotein functionally linked to D1 receptors in striatum.
      Dephospho-form of DARPP-32 in striatal tissue was measured by a back
      phosphorylation assay. While the levels of DARPP-32 protein, as measured by
      quantitative immunoblotting, remained unchanged, a significant decrease of
      dephospho-DARPP-32 was observed in the denervated striatum of primed rats,
      indicating an increased phosphorylation in vivo of DARPP-32 in response to the D1
      agonist. This study shows that an alteration of the dopamine-dependent signal
      transduction is related to the behavioral response to dopamine agents, suggesting
      a possible mechanism involved in the effects of these drugs in parkinsonian
      patients.

PMID- 8748614
TI  - Is in vivo striatal acetylcholine output under a tonic inhibitory control by
      dopamine?
AB  - The role of dopamine transmission on striatal acetylcholine release was
      investigated by using brain microdialysis. Blockade of dopamine D2 receptors with
      (-)-sulpiride or haloperidol increased acetylcholine release to a maximum of 80%
      (after 50 and 0.5 mg/kg, respectively). This effect was prevented by blockade of
      dopamine D1 receptors with 0.5 mg/kg SCH 39166 or by depletion of dopamine stores
      after 5 mg/kg reserpine + 150 mg/kg alpha-methyltyrosine. Treatment with SCH
      39166 or reserpine + alpha-methyltyrosine reduced acetylcholine release by about
      a maximum of 30%. Stimulation of dopamine D2 receptors with LY 171555
      (quinpirole) at a low, sedative dose (0.05 mg/kg), reduced acetylcholine release
      by about 30% with no further reduction at higher doses up to 1 mg/kg. Moreover,
      LY 171555 (0.1 mg/kg) given to SCH 39166 (0.5 mg/kg) or SKF 38393 (20 mg/kg)
      pretreated rats did not decrease acetylcholine release, suggesting that its
      effect is through a dopamine D1 receptor-mediated mechanism. In contrast, in
      dopamine depleted rats, LY 171555 0.1 mg/kg became more effective in decreasing
      acetylcholine release (about 70%) also after SCH 39166 (0.5 mg/kg) pretreatment
      (about 80%), thus acting independently of dopamine D1 receptor mechanisms. These
      results indicate that, in normal circumstances, endogenous dopamine facilitates
      striatal acetylcholine release through dopamine D1 receptors. The results argue
      against the commonly accepted view that dopamine D2 receptors exert a tonic
      inhibitory control on acetylcholine release. Moreover, they suggest that dopamine
      D2 receptors, in circumstances of dopamine depletion, may exert an inhibitory
      control on acetylcholine release independent of dopamine D1 receptor mechanisms.

PMID- 8748615
TI  - DOPA-induced "peak dose" dyskinesia: clues implicating D2 receptor-mediated
      mechanisms using dopaminergic agonists in MPTP monkeys.
AB  - Dopa-induced "peak dose" dyskinesia (DID) observed during the treatment of
      Parkinson's disease patients has traditionally been linked primarily to dopamine
      D1 receptor-mediated mechanisms. However, in MPTP-induced parkinsonian monkeys
      with DID, the administration of selective dopamine D1 or D2 agonists will, in the
      case of D1 agonists result in similar antiparkinsonian effect but with much less
      dyskinesia. Thus, once primed, enhanced D1 neural transmission might in fact
      benefit DID. In drug-naive MPTP monkeys, the high dyskinetic potential of several
      selective D2 agonists and the more favorable outcome on dyskinesia resulting from
      the continuous stimulation of D2 receptors (leading to D2 receptor down
      regulation) are important clues suggesting the primary role played by D2 receptor
      mediated mechanisms in the dyskinesia priming process. Further clinical studies
      using drugs selective for the various dopamine receptor subtypes and of different
      efficacy half-lives are needed to validate our primate data.

PMID- 8748616
TI  - Alterations of striatal dopamine D2 receptors contribute to deteriorated response
      to L-dopa in Parkinson's disease: a [123I]-IBZM SPET study.
AB  - Single photon emission tomography with the ligand [123I]-IBZM was used to image
      central dopamine D2 receptors in Parkinson's disease patients. The aim was to
      assess striatal receptor densities in relation to response to L-Dopa therapy. In
      the parkinsonian patients group who were untreated until SPET study and in the
      group of patients with a sustained response to chronic L-Dopa, striatal [123I]
      IBZM uptake did not differ significantly from mean values of the control group.
      On the contrary, significantly diminished uptake of [123I]-IBZM was found in the
      basal ganglia regions of the group of patients who developed a
      complicated/fluctuating response to chronic L-Dopa treatment. Our results
      indicate that striatal D2 receptor alterations in Parkinson's disease may
      contribute to the altered response to L-Dopa.

PMID- 8748617
TI  - PET studies of the striatal dopaminergic system in Parkinson's disease (PD).
AB  - Positron emission tomography (PET) is a functional imaging technique which allows
      detection of biochemical and pharmacological dysfunction of the nigrostriatal
      dopaminergic system and provides the opportunity to investigate living patients
      with PD. This paper reviews the contribution of PET studies to the understanding
      of neurochemical changes underlying Parkinson's disease.

PMID- 8748618
TI  - Apomorphine continuous stimulation in Parkinson's disease: receptor
      desensitization as a possible mechanism of reduced motor response.
AB  - Apomorphine is a potent nonselective agonist at D1 and D2 dopamine receptors. The
      utility of apomorphine in Parkinson's disease (PD) is well asserted but its
      clinical use is reduced because of its short half-life and numerous side-effects.
      The disabling "on-off" fluctuations are among the most frequent and troublesome
      complications of chronic levodopa therapy in PD. Apomorphine is effective to
      reverse refractory L-dopa induced "off" periods, but a reduced motor response
      after repeated administrations has also been described with this drug. The loss
      of response to apomorphine, when the drug is administered repeatedly, is well
      fitted by the processes of receptor phosphorylation and down regulation.
      Elucidation of the molecular bases of dopaminergic receptors desensitization may
      lead to a better understanding of the mechanisms of dopaminergic regulation, and
      to a more appropriate treatment of PD.

PMID- 8748619
TI  - Pharmacokinetics of apomorphine in Parkinson's disease.
AB  - The pharmacokinetic properties of apomorphine in patients with Parkinson's
      disease are described. Apomorphine is lipophilic; it has a large volume of
      distribution and is rapidly cleared from plasma, with an elimination half life of
      33 minutes. It is rapidly absorbed following subcutaneous injection, with peak
      levels achieved within 5-10 minutes in most patients. There is a large variation
      in absorption between patients but is more constant within patients following
      repeated dosing. Apomorphine rapidly equilibrates between plasma and brain. Like
      levodopa, the response tends to be largely "all or none"; larger doses produce a
      longer duration of effect within a 30-90 minute range. Apomorphine may be
      administered intranasally and sublingually; of these routes, the former is more
      quickly and completely absorbed. Other routes of administration, including
      rectally, are not as well absorbed but may also be used effectively.

PMID- 8748620
TI  - Injection of apomorphine--a test to predict individual different dopaminergic
      sensitivity?
AB  - Male rats, treated with apomorphine (APO: 2mg/kg s.c.) in an Animex-Motility
      Meter, showed individually different motility patterns, each expressed by oral
      stereotyped behaviour and enhanced locomotor activation reproducible in a second
      test 4 days later. One group of the rats showed stereotyped sniffing with an
      increased locomotor activation, S(L,G)-rats, being predominantly "mesolimbic
      active" rats. The other groups could be classified as mainly licking or gnawing
      rats, L(S,G)-rats or G(L,S)-rats, with less increase of locomotor activation,
      resembling predominantly "nigrostriatal active" rats. The G(L,S)-rats seemed to
      be mostly "nigrostriatal active". In this study the different types of rats were
      treated with neuroleptic drugs in presence of APO. Haloperidol (HAL; 0.2 and 0.4
      mg/kg i.p.) had a clear dose dependent antagonizing effect on APO-induced
      stereotypies and locomotor activity: a pronounced effect on the L(S,G)- and
      G(L,S)-rats and less on S(L,G)-rats. In contrast, clozapine (CLO; 10 and 15 mg/kg
      i.p.) did not antagonize the stereotyped behaviour in the rats tested but showed
      a characteristic shift in the S(L,G)- and G(L,S)-rats: the predominant stereotypy
      of these rats, quantified by scoring, changed to licking. In the L(S,G)-rats the
      predominant licking stereotypy was not changed and the locomotor activity, which
      was completely antagonized in the S(L,G)- and G(L,S)-rats at both CLO-doses, was
      affected by 15 mg/kg, only. Furthermore, after the combined treatment with APO
      and HAL or APO and CLO these rat-types also differed in their amount of ACTH and
      corticosterone release. DA-1/DA2 and/or DA-1/DA3 receptor mechanisms may be
      involved in these individually different motility patterns and endocrine
      reactions. In summary, pretesting of rats with APO and measuring the motility and
      endocrine parameters may give us information on a preexisting different
      sensitivity of individuals to react to DAergic stimulation.

PMID- 8748621
TI  - Sublingual apomorphine: a new pharmacological approach in Parkinson's disease?
AB  - Apomorphine, a potent dopamine agonist with mixed D1 and D2 properties, has long
      been recognized to have antiparkinsonian effect. Its oral administration is
      limited by both its hepatic first pass metabolism and adverse side effects
      (nausea, vomiting, azotemia). It is now widely used by subcutaneous route for the
      treatment of severe "off" periods seen with levodopa treatment. However, the use
      of penjects can be difficult in some patients with severe tremor or akineto-rigid
      symptoms during "off" periods. Our group has recently investigated the effect of
      sublingual administration of apomorphine in patients suffering from Parkinson's
      disease. Sublingual apomorphine was shown to reduce extrapyramidal symptoms. The
      main characteristics of the pharmacodynamic effects of sublingual apomorphine in
      parkinsonians and the relationship between pharmacodynamic and pharmacokinetic
      effects are discussed. Sublingual apomorphine has the advantage of being easier
      to administer than subcutaneous injection. For the moment, the long-term use of
      sublingual apomorphine is limited by two major problems: first, time for
      dissolution and switch "on" (which is longer than after subcutaneous route) and
      secondly, the occurrence of local side effects (stomatitis). Further clinical
      studies using either more efficient (tablets with faster dissolution) and better
      tolerated sublingual formulations or other dopamine agonists should be carried on
      before recommending this approach in the treatment of Parkinson's disease.

PMID- 8748622
TI  - Apomorphine SC treatment in parkinsonian patients with long-term L-dopa syndrome
      during L-dopa drug holiday.
AB  - The Long-Term Dopa Syndrome (LTDS) is one of the main problems in the management
      of advanced parkinsonian patients. A transient L-Dopa withdrawal (Drug Holiday,
      DH) can be useful to improve the drug response after DH, even if this approach
      presents risks due to patient akinesia. We tried to verify if Apomorphine sc
      administration during DH (DH with Apomorphine, DHA) can: a) reduce the risks
      connected with DH: b) maintain the benefits of DH: c) standardize the duration of
      DH. Twenty-five parkinsonian patients with LTDS were treated with Apomorphine sc
      during DH (14 days). No patient had any severe side effects. The follow-up at 180
      days, conducted using the Unified Parkinson's Disease Rating Scale, demonstrated
      a significant improvement in the clinical conditions of about 70% of the
      patients, allowing a 27.1% reduction in daily L-dopa dosage. DHA can represent a
      valid therapeutical approach for parkinsonian patients with LTDS.

PMID- 8748623
TI  - Changes in the amplitude of the N30 frontal component of SEPs during apomorphine
      test in parkinsonian patients.
AB  - Somatosensory evoked potentials (SEPs) to median nerve stimulation have been
      performed before and after apomorphine-test in 10 parkinsonian patients. Latency
      and amplitude of the P14-N20 parietal complex and of the P20-N30 frontal complex
      were evaluated. The N30 amplitude was significantly reduced before apomorphine
      administration (p < 0.001) with a consequent increase of the N20/N30 amplitude
      ratio (p < 0.001). Eight patients clinically improved after Apomorphine.
      Following Apomorphine there was no change in the amplitude of the parietal
      complex P14-N20. On the other hand the frontal complex P20-N30 showed a
      significant amplitude potentiation (p < 0.005), with a reduction of the N20/ N30
      amplitude ratio (ns). This finding was almost constant among the 8 responder
      patients. These results suggest the utility of combining clinical and
      neurophysiological data to assess the responsiveness to dopaminergic treatment.

PMID- 8748624
TI  - N30 wave amplitude of somatosensory evoked potentials from median nerve in
      Parkinson's disease: a pharmacological study.
AB  - We studied N20 and N30 waves of Somatosensory Evoked Potentials from median nerve
      stimulation in different pharmacological conditions. N30 wave amplitude was
      decreased in 33 parkinsonians without therapy in comparison with a group of age
      matched normal subjects. In a group of 19 parkinsonians, N30 wave amplitude was
      significantly augmented during apomorphine infusion and less evidently, but still
      significantly, during chronic 1-dopa therapy. The administration of an oral dose
      of haloperidol in 11 normals did not affect significantly the studied parameters.
      The infusion of apomorphine in 6 psychotic patients with extrapyramidal symptoms
      secondary to long-term treatment with neuroleptics, determined, together with a
      clear-cut clinical amelioration, a significant increase of N30 amplitude and
      N30/N20 ratio. Possible pathophysiological hypothesis of such
      electrophysiological modifications are discussed.

PMID- 8748625
TI  - Dopaminergic agonists in the treatment of Parkinson's disease: a review.
AB  - Dopaminergic agonists represent an important class of drugs in Parkinson's
      Disease, useful: a) in delaying the beginning of L-dopa therapy; b) in supporting
      it, reducing its dosage and widen the therapeutic window; c) moreover, as the
      disease advances, in trying to treat motor fluctuations. Authors describe briefly
      the problems caused by long term L-dopa therapy, and analyze, separately, the
      characteristics of the most important dopaminergic agonists currently utilized in
      the treatment of PD.

PMID- 8748626
TI  - The response of "de novo" Parkinson's disease patients to bromocriptine in a "low
      and slow" regimen is predictive for prognosis.
AB  - It is possible that Bromocriptine only determines a complete antiparkinson effect
      in a subset of P.D. patients that have a good dopaminergic reserve. Our study
      intent to demonstrate that a good short-term response to Bromocriptine used in a
      "low and slow" regimen is a marker of long term good prognosis. We studied a
      series of 36 sequential "de novo" P.D. patients treated with Bromocriptine in a
      "low and slow" regimen. The principal end-point was the introduction of Levodopa.
      "Good prognosis" was defined as no need of Levodopa until five years of follow
      up. An improvement greater than 33% in the Columbia rating scale, at the 6th
      month of treatment, was the cut-off point to decide that a patient had a good
      short term response to Bromocriptine. Nine patients fulfilled the criteria for
      being good short term responders. Multiple regression analysis showed that this
      outcome could not be predicted by the clinical characteristics of the patients at
      admission. The sensitivity and the specificity of the short term response to
      Bromocriptine to predict a good prognosis were 70% and 90.5% respectively. We
      conclude that Bromocriptine in monotherapy is an efficient antiparkinson agent in
      1/3 of "de novo" P.D. patients and good short term response to Bromocriptine is
      an acceptable marker for a good prognosis. Therefore it is possible that the
      response to Bromocriptine is a discriminator for a subset of P.D. patients in the
      early phases of the disease.

PMID- 8748627
TI  - Pergolide mesylate in Parkinson's disease treatment.
AB  - In the past 15 years, clinical data of over 1,500 patients treated with pergolide
      mesylate have been published. Pergolide is a dopamine agonist with a potent
      stimulating effect on D2 and also on D1 receptors. This pharmacodynamic
      characteristic seems the most effective in increasing the motility in Parkinson's
      disease. Pergolide has been used almost exclusively as an adjunct to levodopa
      treatment. Its positive effects seems to be related to its long plasma half life,
      about 27 hours, and 5-6 hours of clinical activity; it has shown to be effective
      on all parkinsonian symptoms except for the reduction of postural reflexes, it
      reduces off periods and compared to bromocriptine, it considerably improves the
      activities of daily living. Adverse reactions are, for the most part, mild and
      reversible, they mostly include nausea and gastroenteric disturbances.

PMID- 8748628
TI  - Second generation of dopamine agonists: pros and cons.
AB  - Dopamine agonists (DAGs) were first used in patients with moderate or advanced
      Parkinson's disease (PD). At that time, it was thought that DAGs could replace
      levodopa (LD) with fewer side effects. However, it soon became clear that while
      they could not replace LD, they did allow reduction of the dose of LD and
      diminished its side effects. Since the use of DAGs reduces response fluctuations
      as well as dyskinesias, there is a tendency to introduce them in the first stages
      of the disease, trying to delay motor fluctuations. While many DAGs have been
      developed, only four have been marketed and are used extensively for the
      treatment of Parkinson's disease: apomorphine, bromocriptine, lisuride and
      pergolide. In the present chapter, following a review of the "old" DAGs, the
      experience with three new promising DAGs is reported: cabergoline, ropinirole and
      pramipexole.

PMID- 8748629
TI  - The use of pramipexole, a novel dopamine (DA) agonist, in advanced Parkinson's
      disease.
AB  - We evaluated the efficacy, safety and tolerability of a new dopamine D-2 receptor
      agonist, pramipexole [(S)-2-amino-4,5,6,7-tetrahydro-6-propylamino-benzathiazol
      dihydro chloride], as adjunctive therapy in patients with advanced Parkinson's
      disease (PD). Twenty-four PD patients with motor fluctuations were treated in an
      11 week prospective, single-blind parallel-group, placebo-controlled trial. The
      pramipexole treated group experienced a significant improvement in "off" time
      functioning as measured by the activities of daily living portion of the United
      Parkinson's Disease Rating Scale. In addition, the active treatment group was
      able to reduce total levodopa dose by 30% (p < 0.05). Pramipexole was well
      tolerated and the side effects reported were typical of other dopamine agonists.
      We conclude that pramipexole has antiparkinsonian effects which make it
      potentially useful in the treatment of motor fluctuations in PD.

PMID- 8748630
TI  - Ropinirole in the symptomatic treatment of Parkinson's disease.
AB  - Ropinirole is a novel, non-ergoline dopamine agonist chemical name with a very
      high specificity for dopamine D2-like receptors, currently being investigated for
      the symptomatic treatment of Parkinson's disease. The efficacy of ropinirole has
      been investigated in three placebo-controlled studies: one using ropinirole as
      monotherapy in early Parkinson's disease and two using it as an adjunct to L-dopa
      in patients who are experiencing fluctuations in motor response. Ropinirole
      therapy for 12 weeks was an effective symptomatic therapy in both patient groups,
      as measured by either a significant improvement in the motor score of the UPDRS,
      reduction of awake time spent "off" or a reduction in the dose of L-dopa.
      Ropinirole therapy was generally well tolerated, the most frequent adverse events
      being nausea and vomiting which are typical of all dopamine agonists, but unlike
      other dopamine agonists, CNS side-effects were of the same magnitude as found
      patients receiving placebo.

PMID- 8748631
TI  - Dihydroergocryptine in the treatment of Parkinson's disease.
AB  - In the last 20 years dopamine agonists have been considered more and more helpful
      as primary therapy for Parkinson's disease (PD). Recently the neuroprotective
      activity and the therapeutic efficacy of a new ergot derivative, alpha
      dihydroergocryptine (DHEC), has been highlighted. In the present work we resume
      the experimental and clinical data reported about this drug. The rationale for
      dopamine (DA) agonists as primary therapy for Parkinson's disease (PD) is based
      on the possibility to delay the onset of long term I-dopa syndrome (LTS) (King,
      1992); moreover DA agonists seem to exert a neuroprotective effect on substantia
      nigra neurons. In fact, they stimulate DA receptors bypassing the degenerating
      nigrostriatal neurons and their metabolic machinery (Lieberman, 1992; Olanow,
      1992); more recently, some studies have shown that these drugs have a direct
      protective effect too (Felten et al., 1992; Yoshikawa et al., 1994). In this
      minireview we resume the data reported about neuroprotective activity and
      therapeutic efficacy of a new ergot derivative, alpha-dihydroergocryptine (DHEC).

PMID- 8748632
TI  - Lack of pharmacokinetic interaction between the selective dopamine agonist
      cabergoline and the MAO-B inhibitor selegiline.
AB  - The addition of a dopamine agonist and of a monoamine oxidase type B inhibitor to
      I-dopa has been suggested in the therapy of Parkinson's disease. The plasma
      pharmacokinetics of both cabergoline and I-dopa have previously been shown to
      remain unaffected when the two drugs are given concomitantly. This study aimed at
      examining whether the plasma pharmacokinetic parameters of cabergoline and
      selegiline are modified when given in combination. Selegiline is hardly
      detectable in plasma. Therefore, the plasma levels of its metabolites
      amphetamine, methamphetamine and desmetylselegiline were used to assess the
      effect of cabergoline co-administration. Plasma levels of the selegiline
      metabolites were determined first after selegiline administration (10 mg/day) for
      8 days, and then after administration of both drugs for 22 additional days (day
      30). Cabergoline plasma levels were measured on day 30, and then after
      administration of cabergoline (1 mg/day) alone for further 22 days. No
      statistical difference was found between the Cmax.ss, tmax.ss, AUC0-24h.ss,
      C0h.ss, C24h.ss values of cabergoline and of the selegiline metabolites when the
      two drugs were given alone or in combination, indicating the absence of
      pharmacokinetic interaction between cabergoline and selegiline.

PMID- 8748633
TI  - Cabergoline improves motor disability without modifying L-dopa plasma levels in
      fluctuating Parkinson's disease patients.
AB  - Studies on the influence of some dopamine agonists, particularly bromocriptine,
      on the pharmacokinetics of L-dopa have furnished contrasting results. Thus, any
      possible pharmacokinetic interaction should be taken into consideration when
      adding a new dopamine agonist to L-dopa treatment. In 12 Parkinson's disease (PD)
      patients with motor fluctuations, cabergoline was added in an 8-week study to
      their usual L-dopa/carbidopa therapy. Cabergoline was administered once a day at
      increasing doses of 0.5, 1, 2, and 3mg/day for a period of one week per dose, and
      4mg/day for three weeks. Motor performance was assessed weekly evaluating the
      motor examination of the Unified Parkinson's Disease Rating Scale (UPDRS) and the
      patients' diaries of daily on-off time. Blood levels of both L-dopa and 3-O
      methyldopa (3-OMD) were assayed by HPLC in two different days, over an 8-hour
      period, before initiating cabergoline and at the end of the study. The results of
      this study confirm that cabergoline is effective in the management of PD motor
      fluctuations without modifying L-dopa and 3-OMD pharmacokinetics.

PMID- 8748634
TI  - Plasma levels of vitamin E in Parkinson's disease.
AB  - We report the analysis of plasma levels of vitamin E that has been found normal
      in 20 italian patients with Parkinson's disease (PD) confirming the previously
      reported results from other groups. We discuss the literature data about the
      possible protective effect of antioxidant agents in the PD and generally in the
      aging processes.

PMID- 8748635
TI  - Interaction of neuroprotective substances with human brain superoxide dismutase.
      An in vitro study.
AB  - Human brain total superoxide dismutase activity (SOD) was assayed in the presence
      of increasing concentrations of neuroprotectives. Superoxide-dependent
      nitrobluetetrazolium (NBT) reduction served as control for direct radical
      interaction of these substances. High concentrations of the dopamimetic
      substances L-DOPA slightly and the monoamine oxidase B inhibitor selegiline more
      effectively inhibit SOD activity. The MAO-B inhibitor RO 16-6491 (N-(2
      aminoethyl)-4-chlorobenzamide hydrochloride) has no effect on SOD enzyme
      activity. Reduced glutathione stimulates SOD activity. Moreover it exhibits
      slight activity in scavenging radicals in vitro. Oxidized glutathione and vitamin
      E are unable to do so. Ascorbic acid mimics the activity of reduced glutathione,
      but directly interacts with NBT reduction. Thioctic acid shows no effect on SOD
      activity but stimulates superoxide-dependent NBT reduction. The Ginkgo biloba
      extract EGb 761 is highly active in inhibiting superoxide-dependent NBT reduction
      as well as SOD activity.

PMID- 8748636
TI  - Effects of acute n-hexane and 2,5-hexanedione treatment on the striatal
      dopaminergic system in mice.
AB  - In order to investigate the effect of n-hexane and its metabolites on the Central
      Nervous System (CNS), we treated mice with n-hexane and 2,5-hexanedione (2,5-HD)
      by intraperitoneal (i.p.) administration. Gascromatographic mass spectrometric
      (GCMS) analyses of striatum and cerebellum revealed a consistent increase of 2,5
      HD concentration at 0.5 and 2 hours after treatment and a decline to baseline
      levels at 24 hours. Traces of 2,5-HD were detected in the brain of control
      animals. Biochemical analyses revealed a precocious, short lasting, significant
      increase of striatal dopamine (DA) and homovanillic acid (HVA) levels. A
      significant increase of striatal synaptosomal DA uptake, suggesting a DA
      releasing effect on the dopaminergic terminals, was also observed. These results
      support the hypothesis of a possible role of n-hexane and its metabolites in
      inducing parkinsonism in humans and animals.

PMID- 8748637
TI  - Molecules with neurotrophic effects on the human developing mesencephalic
      dopaminergic neurons.
AB  - Parkinson's disease (PD) is characterized by the degeneration of the
      mesencephalic dopaminergic (mesDA) neurons innervating the striatum. Neurotrophic
      factor(s) that prevents the degeneration and increases the functional activity of
      the remaining mesDA neurons are of substantial clinical interest. The origin and
      development of mesDA neurons were characterized in the human mesencephalon from
      5.0 to 12 Postconception (PC) weeks. Tyrosine Hydroxylase (TH) immunoreactive
      cells were first demonstrated at 5.5 PC weeks next to the ventricular zone. In
      primary culture, TH immunoreactive neurons represent 3 to 5% of the total cells
      at days 7 in vitro and basic Fibroblast growth factor (bFGF) was demonstrated to
      induce a significant increase of both TH immunoreactive cell number and TH
      enzymatic activity. This effect was mediated by proliferating glial fibrillary
      acidic protein immunoreactive cells. Nerve growth factor treatment did not have
      any appreciable effect. The effect of bFGF on TH positive cells described in this
      human bioassay is only a preliminary evidence that, if confirmed by experiments
      in vivo, may provide a starting rationale for investigating alternative
      strategies in the treatment of PD.

PMID- 8748638
TI  - The inhibition of peroxide formation as a possible substrate for the
      neuroprotective action of dihydroergocryptine.
AB  - Dihydroergocryptine is an ergot alkaloid endowed with pharmacological actions
      mainly related to its dopaminomimetic activity. Free radical formation and
      subsequent lipid peroxidation had been postulated to participate broadly to the
      pathogenesis of tissue injury, including the brain injury induced by hypoxia,
      ischemia or trauma, as well as in the physiopathology of chronic
      neurodegenerative diseases, such as Parkinson's disease. Here we report that
      dihydroergocryptine protects cultured rat cerebellar granule cells against age
      dependent and glutamate-induced neurotoxicity. Dihydroergocryptine antagonizes in
      fact both the neuronal death produced by acute exposure to a toxic glutamate
      concentration as well as the normal age-dependent degeneration in culture,
      presumably by exerting a scavenger action. This effect does not seem mediated
      entirely by interactions with the dopamine D2 receptors. The neuroprotective
      action of dihydroergocryptine suggests a potential usefulness in halting the
      acute and chronic neurodegenerative diseases related to excitotoxic damage and
      free radical formation, including Parkinson's disease.

PMID- 8748639
TI  - Neuroprotective activity of alpha-dihydroergocryptine in animal models.
AB  - alpha-Dihydroergocryptine (alpha-DHEC) is a well known dopaminergic agent
      successfully employed in the treatment of Parkinson's disease. alpha-DHEC showed
      a neuroprotective activity against total cerebral ischemia induced by MgCl2 in
      mice and histocytic anoxia by NaCN in mice and rats. Moreover the drug promoted
      the recovery of locomotor activity in rats after cerebral ischemic damage and
      protected mice against convulsions induced by intracerebroventricular injections
      of NMDA and glutamate. alpha-DHEC showed a protective activity on neuronal
      degeneration induced by MPTP in monkeys, as evaluated through animal's behaviour
      and morphological-cytochemical changes in the substantia nigra, suggesting a
      preservative effect on neuronal morphology and brain architecture. In the MPTP
      treated monkeys, the alpha-DHEC administration induced a restoration of the
      unstimulated MDA values to control levels. The neuroprotective activity of alpha
      DHEC is related to its peculiar activity on antioxidative enzymes of GSH system
      and to reduction of lipid-peroxide-induced cellular degeneration.

PMID- 8748640
TI  - A simple model for deuterium cross-polarization magic-angle spinning nuclear
      magnetic resonance at the interphases of amorphous materials.
AB  - The structure and composition of the interphase at the boundary of two immiscible
      phases has long been the subject of experimental and theoretical studies in
      polymer science. Cross-polarization between protons and deuterons offers the
      potential for elucidating the composition of the interphase if one of the
      immiscible phases is deuterated. A prerequisite for such an analysis is the
      establishment of an experimental protocol for reliable spin counting in 1H-2H
      cross-polarization magic-angle spinning (CP-MAS) spectroscopy. In this paper we
      present a simple model for the quantitative analysis of deuterium CP-MAS spectra.
      The model will be applied to the characterization of the polystyrene-b
      poly(methyl methacrylate) interphase in a subsequent publication.

PMID- 8748641
TI  - Nuclear magnetic resonance investigation of the structures of phosphate and
      phosphate-containing glasses: a review.
AB  - This paper presents a review of the nuclear magnetic resonance (NMR) data for
      phosphate and phosphate-containing glasses obtained primarily within the past 10
      years and of the structural interpretations based on those data. Compositions
      discussed include P2O5, alkali and alkaline earth phosphates, aluminophosphates,
      borophosphates, fluorophosphates, and phosphate-containing silicate and
      aluminosilicate glasses. 31P NMR data, in conjunction with 27Al, 29Si, 11B, 7Li,
      and 23Na data if appropriate, have proven very powerful in providing direct
      evidence about the local structural environments present in the these materials
      and in many cases have allowed interpretation of the physical and chemical
      behavior of these glasses in terms of polyhedral structures.

PMID- 8748642
TI  - Magic-angle spinning nuclear magnetic resonance study of the structure of some
      PbO-Al2O3-P2O5 glasses.
AB  - Some PbO-Al2O3-P2O5 glasses have been investigated using 31P and 27Al magic-angle
      spinning nuclear magnetic resonance. The observed spectra could be divided into
      two groups. In the first, Al(IV), Al(V) and Al(VI) are observed, the 31P
      linewidths are large and the chemical shift range (-30 to -36 ppm) is typical of
      network phosphate. In the second group, only Al(VI) is observed, the 31P
      linewidths are much narrower and the shifts are less negative (-18 to -28 ppm).

PMID- 8748643
TI  - Nuclear magnetic resonance study of a high-surface-area aluminum phosphate glass
      and its thermally reversible sol-gel precursor.
AB  - A novel reaction, based on sol-gel chemistry using an aluminum alkoxide and
      phosphoric acid to produce a high-surface-area aluminum phosphate glass, was
      followed by 27Al and 31P nuclear magnetic resonance (NMR). The gelled portion of
      the alcoholic solutions could be characterized with solid state 27Al methods. We
      discovered that the gelation, which is very rapid under normal conditions, can be
      controlled by the addition of HCl to the solution and that the gelation is
      thermally reversible in the presence of HCl. The NMR results showed that this
      modified sol-gel behavior is a result of acid hydrolysis of the Al-O-P bonds,
      leading to network termination by POH groups and octahedrally solvated Al atoms.
      Similar local structures persist in the amorphous calcination product. The glass
      surface contains Al sites with strong quadrupole interaction. These sites could
      not be detected by conventional 27Al NMR methods but their existence was
      demonstrated with a static echo experiment. The quadrupole coupling constant was
      determined with the recently introduced transfer of populations in double
      resonance (TRAPDOR) method (a 1H/27Al double resonance magic-angle spinning
      experiment). The TRAPDOR results also showed that these sites, which constitute
      about 30% of the Al in the glass, carry hydroxyl groups. Characterization of the
      atomic structure of high-surface AlPO4 is important for its use as catalyst
      support.

PMID- 8748644
TI  - Detection of multiple boron sites in glasses by 11B satellite transition nuclear
      magnetic resonance spectroscopy.
AB  - The magic-angle spinning sidebands of the satellite transition (ST, m = +/- 3/2
      <==> +/- 1/2) for 11B nuclear magnetic resonance (11B ST spectroscopy) have been
      used to detect multiple boron sites in Na2O-B2O3-SiO2 glasses. The experimental
      details and data analysis are described, how multiple BO4 and BO3 units can be
      distinguished using standard magic-angle spinning. For a 16Na2O-30B2O3-53.9SiO2
      glass (0.1 MnO) two BO4 units with chemical shifts of -2.5 and 0 ppm were found
      which differ considerably in their quadrupole interaction. Besides this we found
      three different BO3 units with approximate chemical shifts of 17, 15, and 19 ppm.
      The results are compared with earlier measurements.

PMID- 8748645
TI  - Deconvolution of 29Si magic-angle spinning nuclear magnetic resonance spectra of
      silicate glasses revisited--some critical comments.
AB  - It is common practice to quantify 29Si magic-angle spinning nuclear magnetic
      resonance (MAS NMR) spectra of silicate glasses by using lineshape fitting
      routines based on Gaussian distribution functions. This procedure depends on
      several -implicit -assumptions. In this contribution we have addressed and
      questioned these underlying assumptions. Also "goodness-of-fit" criteria and
      experimental considerations ("goodness-of-data") have been discussed. Some
      illustrative practical examples (silica glass, binary Na2O-SiO2 glasses with
      different Na:Si ratio) are given.

PMID- 8748646
TI  - 27Al magic-angle spinning nuclear magnetic resonance satellite transition
      spectroscopy of glasses in the system K2O-Al2O3-SiO2.
AB  - 27Al magic-angle spinning nuclear magnetic resonance satellite transition
      spectroscopy at 78 MHz has been applied to determine (true) chemical shift and
      quadrupole coupling parameters of glasses in the system K2O-Al2O3-SiO2 with 60-80
      mol% SiO2 and K2O concentrations between 0 and 24 mol%. The powdered crystalline
      aluminosilicates andalusite and sillimanite have also been examined. In the
      glasses, all Al appears to be tetrahedrally bound in the aluminosilicate network
      unless x = mol% K2O:mol% Al2O3 becomes extremely small. Upon decreasing x the
      distortion of the tetrahedral Al(OSi)4 units increases in steps, and possible
      explanations are discussed. Six-coordinated aluminum observed for x < 0.2 is
      connected with the occurrence of interstitial Al3+ ions which charge-compensate
      the AlO4 units in addition to K+.

PMID- 8748647
TI  - One- and two-dimensional 1H magic-angle spinning experiments on hydrous silicate
      glasses.
AB  - Applications of various one- and two-dimensional 1H magic-angle spinning nuclear
      magnetic resonance (MAS NMR) techniques for the elucidation of structural
      properties of hydrous silicate glasses are described. Advantages and limitations
      of one-dimensional experiments [MAS and combined rotation and multiple-puls
      spectroscopy (CRAMPS)] and of two-dimensional approaches (spin-exchange
      experiments, "MAS-CRAMPS" correlation plus extended versions) are discussed. The
      various 1H MAS NMR techniques are illustrated by practical examples of spectra
      obtained from a hydrous silicate glass of Na2O.4SiO2.0.7H2O composition.

PMID- 8748648
TI  - 6Li nuclear magnetic resonance chemical shifts, coordination number and
      relaxation in crystalline and glassy silicates.
AB  - Unlike 7Li magic-angle spinning nuclear magnetic resonance (MAS NMR) spectra, 6Li
      MAS NMR spectra of silicates are dominated by chemical shift effects, often have
      a very high resolution and hence can provide significant structural information.
      In this study we demonstrate a good correlation between 6Li isotropic chemical
      shifts and oxygen coordination number, and use this result to describe the range
      of coordination environments for Li in silicate glasses. We also show that the
      second-order quadrupolar shift for 7Li can often be derived from 7Li and 6Li MAS
      spectra acquired at a single magnetic field. For a series of natural lepidolite
      samples with significant but varying contents of Mn and Fe, spin-lattice
      relaxation data show a power-law behavior and a three-dimensional distribution of
      paramagnetic centers, but homonuclear dipolar couplings can be important. The 6Li
      spectrum for lithium orthosilicate (which has three-, four-, five- and six
      coordinated Li) is consistent with that predicted by the X-ray structure.

PMID- 8748649
TI  - 23Na nuclear magnetic resonance spin echo decay spectroscopy of sodium silicate
      glasses and crystalline model compounds.
AB  - The possibility of using Hahn spin echo decay spectroscopy for measuring 23Na
      23Na dipole-dipole couplings in crystalline solids and glasses is investigated.
      Although the presence of nuclear electric quadrupolar splittings complicates the
      situation compared to the case of dipole-dipole couplings among spin-1/2 nuclei,
      experimentally measured second moments lie within approximately 10-20% of the
      calculated values, if the following conditions are fulfilled: (1) selective
      excitation of the central 1/2-->-1/2 transition, and (2) restriction of the
      analysis to short evolution times (2t1 < or = 200 microseconds). At longer
      evolution times, partial suppression of the spin-exchange term in the dipolar
      Hamiltonian due to magnetic inequivalencies between the interacting nuclei
      produces substantial differences between experimental and calculated spin echo
      decays, the extent of which depends on the compound considered. These results
      signify the potential utility of 23Na spin echo nuclear magnetic resonance for
      testing the distribution of Na-Na distances in structurally disordered solids and
      glasses. The method is shown to be applicable to sodium silicate glasses, where
      it reproduces anticipated compositional trends in 23Na-23Na couplings. Details
      and inherent limitations of this methodology are discussed.

PMID- 8748650
TI  - Multi-nuclear and multi-dimensional nuclear magnetic resonance investigation of
      silver iodide-silver phosphate fast ion conducting glasses.
AB  - The results of a multi-nuclear nuclear magnetic resonance (NMR) study of
      (AgI)x(Ag2O)y(P2O5)1-x-y glasses are reported. Using the two-dimensional variable
      angle correlation spectroscopy experiment, the isotropic and anisotropic chemical
      shift interactions of phosphorus were determined as a function of silver iodide
      and silver oxide composition. From these measurements we determine the average
      conformation of the phosphate groups. In addition, the 109Ag NMR spectra were
      recorded, as a function of both composition and temperature. At high silver oxide
      concentrations, interaction between the silver and phosphate groups has been
      detected, but in glasses in the series the (AgPO3)x(AgI)1-x 31P NMR is strikingly
      independent on the silver iodide composition. The temperature dependence of the
      silver NMR linewidths in these systems shows clearly the silver mobility, and at
      lower temperatures no evidence for multiple distinct silver binding sites was
      observed. The silver chemical shift is strongly dependent on both composition and
      temperature. The former effect is interpreted in terms of the influence on the
      chemical shift of binding to oxygen versus iodine.

PMID- 8748651
TI  - Examination of the mixed-alkali effect in (Li,Na) disilicate glasses by nuclear
      magnetic resonance and conductivity measurements.
AB  - Results from 29Si, 23Na and 7Li magic-angle spinning nuclear magnetic resonance
      (NMR) spectroscopy, 7Li NMR relaxation and electrical conductivity in a series of
      [Li(1-x).Nax]2O.2SiO2 (disilicate) glasses are used to investigate the mixed
      alkali effect. From the 29Si NMR spectra there is relatively little change of the
      network with alkali composition. 23Na and 7Li NMR linewidths and shifts change
      continuously as a function of composition, indicating that the alkali ions are
      intimately and uniformly mixed rather than separated into lithium and sodium-rich
      domains. The activation energy from electrical conductivity shows a distinct
      maximum at the central composition (x = 0.5), whereas the local activation energy
      for lithium motion determined from NMR shows only a smaller but monotonic
      increase as the lithium-content decreases.

PMID- 8748652
TI  - The importance of paramagnetic impurities to the nuclear magnetic resonance
      relaxation of ion-conducting glasses.
AB  - Paramagnetic impurities have been shown to affect the 7Li nuclear magnetic
      resonance relaxation rates in cation-conducting glasses, and wrong data may then
      be extracted from the experiments. Frequency- and temperature-dependent T(-1)1
      studies of lithium borate and thioborate glasses revealed that iron impurities
      cause frequency-independent relaxation and "shoulders" of the low-temperature
      slopes in high fields, whereas manganese produces enhanced relaxation peaks. The
      results of the T(-1)1 (and some T(-1)1p and T(-1)2) measurements are discussed.

PMID- 8748653
TI  - Effect of lanthanides on the relaxation rates of 89Y and 29Si in yttrium silicon
      oxynitride phases.
AB  - Additions of paramagnetic lanthanides are found to increase the relaxation rates
      of both 89Y and 29Si in the yttrium silicon oxynitride compounds Y2Si3N4O3 (N
      melilite) and Y4Si2O7N2 (J-phase), allowing the observation of previously
      unreported 89Y magic-angle spinning nuclear magnetic resonance spectra of these
      phases. The dependence of the 89Y and 29Si relaxation rates was determined as a
      function of Yb3+ and Gd3+ concentration. Both the 29Si and 89Y resonances become
      broader with increasing Yb concentration, but at all lanthanide concentrations
      the 89Y spectrum of J-phase is broader than that of N-melilite, possibly due to a
      greater distribution of Y site geometries in the former. At concentrations below
      about 360 mumol g-1, the lanthanide ions appear to be incorporated in the
      lattice, but are not involved in covalent bonding to Y or Si. The effect of a
      series of lanthanides on the 89Y and 29Si relaxation rates and line widths is
      presented in terms of the lanthanide spin quantum numbers and magnetic moments.
      The most effective lanthanide was found to be Eu3+, giving fast relaxation
      (particularly for 89Y) and sharp lines.

PMID- 8748654
TI  - High fraction of penta-coordinated aluminium in amorphous and crystalline
      aluminium borates.
AB  - 27Al and 11B magic-angle spinning nuclear magnetic resonance (MAS NMR) results
      are reported on aluminium borates of composition Al2(1 - x)B2xO3 (0 < or = x < or
      = 0.7). It is shown that starting from liquid precursors with hexa-coordinated Al
      and tri- and tetra-coordinated B, porous aluminium borates are obtained
      containing high fractions of penta-coordinated Al. The presence of boron in the
      crystalline phases stabilizes penta-coordinated Al, existing already in their
      amorphous precursors, and at the same time distorts the surroundings of the hexa
      coordinated Al. The reversible effect of air exposure on low-coordinated Al
      (Al4C, Al5C) and B (B3C) proved that at least these species are situated at the
      surfaces of the pores. The A9B2 phase still contains a small fraction of tetra
      coordinated B. The 27Al and 11B MAS NMR spectra of A9B2 show a well-resolved
      powder spectrum with no indication of broadening due to a distorted
      configuration.

PMID- 8748655
TI  - Double rotation and magic-angle spinning nuclear magnetic resonance study of
      27Al: reexamination of the aluminium borate 9Al2O3.2B2O3.
AB  - 27Al nuclear magnetic resonance spectra of polycrystalline aluminium borate
      9Al2O3.2B2O3 have been measured in double rotation at 11.7 and 7.0 T and high
      speed magic-angle spinning at 7.0, 9.4, 11.7, 14.1 and 17.6 T. Spinning sidebands
      from the satellite transitions were observed at 7.0 and 14.1 T. Each of the four
      structural aluminium sites [Al(IV), Al(V)(1), Al(V)(2) and Al(VI)] are observed,
      characterised and assigned in the spectra. The obtained parameter set gives a
      fully consistent interpretation in agreement with the crystal structure of the
      compound.

PMID- 8748656
TI  - Spin-5/2 Hahn echoes in solids.
AB  - The Hahn echoes for a spin I = 5/2 system were derived by considering the first
      order quadrupole interaction throughout the experiment. Consequently, our results
      are valid for any ratio of the quadrupole coupling, omega Q, to the amplitude of
      the RF pulse, omega RF. The use of simplified density operators reduced the
      computation time dramatically. Furthermore, this approach allows a better
      understanding of the origin of the Hahn echoes in half-integer quadrupole spins.
      The tau 4 = tau 2 Hahn echoes were illustrated with the 27Al nucleus in a
      polycrystalline sample of KAl(SO4)2.12H2O. The quadrupole coupling constant and
      the asymmetry parameter of 27Al were determined by two methods: from the
      lineshape of the powder pattern and from the variation of the central line
      integrated intensity as a function of the second pulse duration.

PMID- 8748657
TI  - Off-resonance nutation nuclear magnetic resonance study of framework
      aluminosilicate glasses with Li, Na, K, Rb or Cs as charge-balancing cation.
AB  - Framework aluminosilicate glasses with varying charge-balancing cation (Li, Na,
      K, Rb and Cs) have been studied with 27Al and 29Si magic-angle spinning nuclear
      magnetic resonance (MAS NMR) and 27Al on-resonance and off-resonance nutation NMR
      spectroscopy. This first application of off-resonance nutation NMR to disordered
      samples proves that it is a promising technique for the determination of mean
      quadrupole interactions in amorphous systems. Linewidths for Al decrease
      systematically with increasing size of the cation, due to a decrease in the
      quadrupole interaction from 5.0 MHz for the Li glass to 2.8 MHz for the Cs glass.
      A simple point-charge model effectively predicts the decrease in the quadrupole
      interaction. This indicates that the alkali ion is located close to aluminum.
      Looking at the residual linewidth after subtraction of the quadrupole broadening,
      the Al chemical shift distribution does not change significantly with the type of
      alkali ion. The same is true for the observed Si linewidth.

PMID- 8748658
TI  - Application of 129Xe nuclear magnetic resonance to the study of Cu-Y zeolites:
      dehydration and redox effects.
AB  - Copper-exchanged sodium Y zeolites have been studied by using 129Xe nuclear
      magnetic resonance (NMR) spectroscopy. The oxidation state as well as the
      location of copper in the zeolite have been determined for different samples at
      various levels of exchange (lambda = 15, 35, 58%) and hydration, and at different
      stages of redox treatment. Information about the nature of Xe-Cu+ or Xe-Cu2+
      interactions has been obtained by a combination of electron spin resonance (ESR)
      and 129Xe NMR measurements on Cu-Y and Cu-Rho zeolites.

PMID- 8748659
TI  - The neurotrophic effects of ebiratide, an analog of ACTH4-9, on cultured septal
      cells and aged rats.
AB  - The neurotrophic effects of ebiratide, an ACTH4-9 analog, have been examined
      using both fetal rat septal cultures and aged rats. The 5-day treatment with
      ebiratide (10-100 pmol/ml) partially prevented neuronal degeneration that
      occurred in the cultures in which cells were sparsely plated. Ebiratide (10 pmol/
      ml) increased choline acetyltransferase (ChAT) and acetylcholinesterase (AChE)
      activities up to 1.5 and 1.2 times the respective control values in the sub
      confluent cultures. AChE cytochemistry of the cultures has shown that ebiratide
      increased the stained area per cell. Ebiratide subcutaneously administered by
      constant infusion (10 nmol/body/hr) for 4 weeks elevated ChAT activities in the
      septum (35% over control), neocortex (79%) and hippocampus (89%) of aged rats.
      Thus, the present study indicates that ebiratide shares neurotrophic properties
      which may prove beneficial in the therapy for CNS degenerative disorders,
      especially Alzheimer's disease.

PMID- 8748660
TI  - Cyclic AMP enhances acetylcholine (ACh)-induced ion fluxes and catecholamine
      release by inhibiting Na+, K(+)-ATPase and participates in the responses to ACh
      in cultured bovine adrenal medullary chromaffin cells.
AB  - The effects of cyclic AMP (cAMP) on intracellular Na+ concentration ([Na+]i),
      membrane depolarization and intracellular Ca2+ concentration ([Ca2+]i) and the
      involvement of cAMP in acetylcholine (ACh)-induced such cellular events and
      catecholamine (CA) release were studied in cultured bovine adrenal medullary
      chromaffin cells. 8-Bromo-cyclic AMP (8Br-cAMP) and forskolin caused a rise in
      [Na+]i, membrane depolarization and a rise in [Ca2+]i and potentiated these
      responses and CA release to ACh. The effects of 8Br-cAMP or forskolin on ACh
      induced changes of but not on basal level of [Na+]i, membrane potential and
      [Ca2+]i were blocked by tetrodotoxin (TTX, 1 microM). In Na+ deprivated medium,
      forskolin failed to produce an increase in basal [Ca2+]i level and to potentiate
      ACh-induced rise. The similar results as in 8Br-cAMP and forskolin were obtained
      using ouabain, and 8Br-cAMP or foskolin produced no further effects in the
      presence of ouabain. Inhibitors of cAMP-dependent protein kinase not only blocked
      the effects of 8Br-cAMP and forskolin on membrane depolarization, [Ca2+]i rise
      and CA release, but also reduced these responses to ACh. From the similarity
      between the effects of cAMP and those of ouabain on the cellular events and the
      counteraction of the effects of cAMP by ouabain, it may be suggested that cAMP
      produces its effects on ion fluxes and CA release probably via an inhibition of
      Na+, K(+)-ATPase in intact chromaffin and cAMP may participate in the responses
      to ACh.

PMID- 8748661
TI  - Cyclic GMP generation mediated by 5-HT-2 receptors via nitric oxide-dependent
      pathway and its effect on the desensitization of 5-HT-2 receptors in C6 glioma
      cells.
AB  - Serotonin (5-HT)-2 receptor-mediated cGMP generation was investigated in
      comparison with calcium (Ca2+) mobilization in C6 glioma cells. 5-HT enhanced
      cGMP generation, and risperidone and ketanserin potently blocked the response.
      These results indicate that 5-HT-2 receptors are responsible for the cGMP
      generation. 5-HT-induced cGMP production was completely abolished by BAPTA, an
      intracellular Ca2+ chelating agent, or NG-mono-methyl-L-arginine(NMMA), a nitric
      oxide synthase (NOS) inhibitor, suggesting that 5-HT-induced cGMP generation was
      through nitric oxide (NO)-dependent pathway. 5-HT (10 microM)-elicited Ca2+
      mobilization and cGMP generation were reduced to 40 and 15% after pretreatment
      with 10 microM 5-HT for 4 hours. NMMA did not modify 5-HT-induced desensitization
      of either Ca2+ mobilization or cGMP generation, suggesting that NO pathway is
      independent of the desensitization. The present study has demonstrated the nature
      of 5-HT-2 receptor-mediated cGMP generation in C6 glioma cells.

PMID- 8748662
TI  - Characterisation of extracellular amino acids in striatum of freely moving rats
      by in vivo microdialysis.
AB  - To investigate the characteristics of extracellular amino acids released from the
      striatum, we performed in vivo microdialysis in non-anaesthetised, freely moving
      rats. Amino acids were determined after precolumn derivatisation with o
      phthalaldehyde by high-performance liquid chromatography and fluorescence
      detection. The omission of Ca2+ in the perfusion medium partially decreased the
      basal concentration of aspartate and glutamate. This shows that a small fraction
      of basal concentration of aspartate and glutamate is of neuronal origin. The
      effect of high K+ and veratrine stimulation was evaluated in the presence or
      absence of Ca2+ or tetrodotoxin (1 microM). High K+ and veratrine caused a
      remarkable increase in the aspartate and glutamate efflux. The omission of Ca2+
      only partially decreased K(+)-stimulated aspartate and glutamate efflux.
      Tetrodotoxin completely antagonised veratrine-stimulated aspartate and glutamate
      efflux. Although glycine and taurine releases were stimulated by high K+ and
      veratrine, their release was not always antagonised with Ca2+ omission or
      tetrodotoxin inclusion. Thus, the neuronal origin of stimulated release of
      glycine and taurine is unclear. Although tetrodotoxin sensitivity and Ca2(+)
      dependency are regarded as a basic criterion for classical neurotransmitters in
      microdialysis experiments, they should not be adapted to the physiological
      characteristics of the release of amino acids.

PMID- 8748663
TI  - Neuronal protective and rescue effects of deprenyl against MPP+ dopaminergic
      toxicity.
AB  - Intranigral infusion of 1-Methyl-4-phenylpyridinium ion (MPP+, 2.1-16.8 nmol)
      dose-dependently injured nigral neurons as reflected by reduced dopamine levels
      in the ipsilateral striatum four days after the infusion of this toxic metabolite
      of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Coadministration of
      deprenyl (4.2 nmol) with MPP+ into the substantia nigra protected against MPP(+)
      induced moderate (20-50%) but not severe (over 70%) nigral injury as reflected in
      striatal dopamine reductions. However, supplementary treatment with deprenyl
      (0.25 mg/kg, s.c., twice daily for 4 days) after intranigral infusion of MPP+
      significantly rescued nigral neurons from more severe damage caused by a higher
      MPP+ does (8.4 nmol) manifested by a lesser striatal dopamine decrease (-31%)
      compared to the non-deprenyl treated group (-70%). Thus, in addition to the
      blockade of bioactivation of MPTP, deprenyl can protect and/or rescue nigral
      neurons from MPP(+)-induced dopaminergic neurotoxicity. These in vivo data add
      further evidence to suggest that deprenyl, a putative and clinically unproven
      neuroprotective agent, may be of value in slowing the progressive nigral
      degeneration in "early" Parkinson's disease, but may prove to be less so in its
      terminal stages.

PMID- 8748664
TI  - Behavioural effects of adenosine locally applied into ventral hippocampus of
      adult male rats.
AB  - The possible effects of Adenosine (AD), locally applied into the ventral
      Hippocampus (HPCv) on the expression of general motor activity and some
      stereotyped behaviours were studied in adult male rats. Locomotion display was
      recorded in a hole-board equipped with automatic infrared animal activity
      detectors. Stereotyped behaviours were measured by direct inspection by two
      observers. Animals were implanted with microinjection cannulae into the HPCv and
      72 h later they were injected with saline, or increasing doses of AD. In one
      experiment rats were microinjected once with saline or Adenosine and general
      motor activity and exploration were examined. In other experiment, rats were
      injected into the HPCv twice with saline, the AD-receptors antagonist 1,3
      dipropil-methyl-xanthine (DMX) or AD and only stereotyped behaviours were
      examined. Results of Experiment 1 showed that the 40 nMol dose of AD was
      significantly effective to inhibit by about 30% several motor activities such as
      vertical, horizontal and ambulatory behaviours. Results of Experiment 2, showed
      that grooming was not modified by AD but the dose of 10 nMol increased the time
      of immobility by about 3 times over controls. DMX was able to block completely
      the AD effects on immobility. The present results suggest that in the rat AD
      might modulate the hippocampal-mediated expression of some motor and stereotyped
      behaviours induced by unknown environments.

PMID- 8748665
TI  - The yohimbine-induced anticonflict effect in the rat, Part I. Involvement of
      noradrenergic, serotonergic and endozepinergic(?) mechanisms.
AB  - The alpha 2-adrenoceptor antagonist yohimbine has in several previous studies
      been found to produce anticonflict effects comparable to those produced by the
      benzodiazepines (BDZ) in rat punished conflict models. In this and a following
      paper we have tried to elucidate the neurochemical mechanisms underlying these
      effects in a modified Vogel's drinking conflict test. Since yohimbine previously
      has been demonstrated to interfere both with noradrenaline (NA) and serotonin (5
      HT) neurochemistry, and, in addition, shows affinity for the BDZ binding site, we
      have focused on the putative involvement of these neuronal systems in the
      yohimbine-induced anticonflict effect. The alpha 2-adrenoceptor agonist clonidine
      (10 micrograms/kg, i.p.) completely antagonized the anticonflict effect of
      yohimbine (4.0 mg/kg, i.p.), whereas the alpha 1-adrenoceptor agonist ST 587 (1.0
      mg/kg, i.p.) had no effect. The anticonflict effect of yohimbine was totally
      abolished also following lesioning of NA neurons with 6-hydroxy-dopamine. A high
      dose of the mixed beta 1 and beta 2 adrenoceptor antagonist propranolol (8.0
      mg/kg, i.p.) caused a partial blockade of the yohimbine-induced effect in intact
      animals, whereas the selective beta 1-adrenoceptor antagonist metoprolol (4.0
      mg/kg, i.p.) had no significant effect and the alpha 1-adrenoceptor antagonist
      prazosin instead potentiated the anticonflict action. The anticonflict effect of
      yohimbine was dose-dependently antagonized also by the 5-HT precursor L-5
      hydroxytryptophan (25-100 mg/kg, i.p.). The BDZ receptor antagonist flumazenil
      (10 mg/kg, p.o.), as well as Ro 15-4513 (1.0 mg/kg, p.o.), a partial inverse
      agonist at BDZ receptors, partly, but significantly, counteracted the yohimbine
      induced anticonflict effect, whereas low doses of both the chloride channel
      blocker picrotoxin and the GABAA antagonist bicuculline only tended to counteract
      the yohimbine effect. Taken together, the results in the present behavioral paper
      indicate that the anticonflict effect of yohimbine involves both increased NA and
      decreased 5-HT activity, and that direct or indirect activation of BDZ receptors
      may also be involved. Neurochemical findings related to these behavioral results
      are presented in a following paper.

PMID- 8748666
TI  - The yohimbine-induced anticonflict effect in the rat, Part II. Neurochemical
      findings.
AB  - In a companion paper the alpha 2-adrenoceptor antagonist yohimbine was found to
      produce a dose-dependent anticonflict effect in a modified Vogel's conflict test.
      The behavioral data further indicated that noradrenergic and serotonergic neurons
      as well as the benzodiazepine (BDZ) receptor may be involved in the anticonflict
      effect of yohimbine. In the present study the effects on rat brain monoamine
      neurochemistry and GABAA/BDZ receptor function (36Cl-uptake in corticohippocampal
      synaptoneurosomes) of a maximally anticonflict producing dose of yohimbine (4.0
      mg/kg, i.p.) were studied. The levels of rat brain catecholamines and
      indoleamines were measured ex vivo using high performance liquid chromatography
      with electrochemical detection (HPLC-ED). Yohimbine decreased noradrenaline
      levels both in the hippocampus and the hemispheres but instead increased DOPAC
      levels in these brain regions as well as in the limbic forebrain. Yohimbine also
      markedly enhanced DOPA accumulation in the hippocampus and the hemispheres after
      inhibition of 1-aromatic amino acid decarboxylase by means of NSD 1015, whereas
      in the limbic system only a modest increase was obtained. The yohimbine-induced
      effects on the catecholamine synthesis rate were largely abolished in animals
      severely depleted of NA by means of 6-hydroxy-dopamine (6-OH-DA) pretreatment.
      Yohimbine decreased both the 5-HIAA/5-HT quotient (an indicator of 5-HT turnover)
      and 5-HTP accumulation after NSD 1015 in the hemispheres, whereas in the
      hippocampus and the limbic system only 5-HTP accumulation was decreased. The
      yohimbine-induced effect on the indoleamine synthesis rate was not influenced by
      6-OH-DA pretreatment, whereas this effect and that on the catecholamine synthesis
      rate were both abolished by reserpine pretreatment. Neither in vivo nor in vitro
      administration of yohimbine significantly altered baseline or GABA-induced
      accumulation of 36Cl- in corticohippocampal synaptoneurosomes. In conclusion, the
      present study provides neurochemical support for the suggestion that yohimbine
      may exert its anticonflict effect in a modified Vogel's conflict test by
      increasing and decreasing NA and 5-HT neurotransmission, respectively, whereas no
      evidence was obtained for a direct interaction of yohimbine with GABAA/BDZ
      receptor function.

PMID- 8748667
TI  - Effects of dorsal rhizotomy and selective lesion of serotonergic and
      noradrenergic systems on 5-HT1A, 5-HT1B, and 5-HT3 receptors in the rat spinal
      cord.
AB  - Autoradiographic studies were performed in combination with dorsal rhizotomy or
      selective lesion of descending serotonergic or noradrenergic systems in an
      attempt to identify the neuronal cell types endowed with the serotonin 5-HT1A, 5
      HT1B and 5-HT3 receptors in the rat spinal cord. Unilateral sectioning of seven
      dorsal roots (C4-T2) at the cervical level produced a marked decrease
      (approximately-75%, 10 days after the surgery) in the binding of
      [125I]iodozacopride to 5-HT3 receptors in the superficial layers of the
      ipsilateral dorsal horn, further confirming the preferential location of these
      receptors on primary afferent fibres. In addition, a significant decrease
      (approximately 20%) in the binding of [3H]8-OH-DPAT to 5-HT1A receptors and of
      [125I]GTI to 5-HT1B receptors was also observed in the same spinal area in
      rhizotomized rats, suggesting that a small proportion of these receptors are also
      located on primary afferent fibres. The labelling of 5-HT1B receptors was
      significantly decreased (-12%) in the dorsal horn at the cervical (but not the
      lumbar) level, and that of 5-HT3 receptors was unchanged in the whole spinal cord
      in rats whose descending serotonergic projections had been destroyed by 5,7
      dihydroxytryptamine. Conversely, the labelling of 5-HT1A receptors was
      significantly increased in the cervical (+13%) and lumbar (+42%) dorsal horn in
      5,7-dihydroxytryptamine-lesioned rats. Similarly, [3H]8-OH-DPAT binding to 5-HT1A
      receptors significantly increased (+26%) in the lumbar (but not the cervical)
      dorsal horn in rats whose noradrenergic systems had been lesioned by DSP-4. The
      labelling of 5-HT1B receptors was also increased (+31% at the cervical level;
      +17% at the lumbar level), whereas that of 5-HT3 receptors remained unchanged in
      these animals. These data indicate that complex adaptive changes in the
      expression of 5-HT1A and 5-HT1B receptors occurred in the rat spinal cord
      following the lesion of descending monoaminergic systems.

PMID- 8748668
TI  - The selective 5-HT2A receptor antagonist MDL 100,907 counteracts the psychomotor
      stimulation ensuing manipulations with monoaminergic, glutamatergic or muscarinic
      neurotransmission in the mouse--implications for psychosis.
AB  - The present study has shown that a subthreshold dose of the uncompetitive N
      methyl-D-aspartate (NMDA) antagonist MK-801, combined with a subthreshold dose of
      LSD, produces marked locomotor stimulation in monoamine-depleted mice. Likewise,
      MK-801, as well as the muscarine receptor antagonist atropine and the alpha
      adrenoceptor agonist clonidine, were found to interact synergistically with the
      putative 5-HT2 receptor agonist UH-232 to produce locomotor activation in
      monoamine-depleted mice. All these responses were effectively blocked by the
      highly selective 5-HT2A receptor antagonist MDL 100,907. On the other hand, MDL
      100,907 did not antagonize the hyperactivity response produced by clonidine given
      in combination with MK-801 or atropine in monoamine-depleted mice, nor the
      response produced by the mixed DA receptor agonist apomorphine, underlining the
      selectivity in the antagonistic action of MDL 100,907. Furthermore, MDL 100,907
      attenuated the hyperactivity produced in intact mice by such disparate agents as
      MK-801, atropine or the DA uptake inhibitor GBR 12,909. A putative "permissive"
      role of the 5-HT2 receptor in the context of psychomotor activation is discussed,
      as well as its possible importance as target for antipsychotic therapy.

PMID- 8748669
TI  - Effects of pineal indoles on ovarian response to gonadotropin-induced ovulation
      in mice.
AB  - Ovulation was induced in immature mice by injections of pregnant mare serum
      gonadotropin (PMSG) and human chorionic gonadotropin (HCG) spaced 48 hours apart.
      The mice were divided into six groups: one group received intraperitoneal
      injections of normal saline, another group received alcoholic saline which was
      used as the vehicle of pineal indoles, and the remaining groups received
      respectively hydroxyindoleacetic acid (HIAA), melatonin (MEL), methoxytryptamine
      (MTA) and methoxytryptophol (MTP). The pineal indoles were administered 24 hours
      before, on the same day as, 24 hours after and 48 hours after the PMSG injection.
      The mice were sacrificed 24 hours after the HCG injection. The numbers of growing
      primary follicles, multilaminar primary follicles, Graafian follicles,
      preovulatory follicles and corpora lutea in the ovary were not altered by
      treatment with pineal indoles. However, there was an increased incidence of
      follicular atresia in the groups treated with MEL, MTA and MTP. The pineal
      indoles did not affect the number of ovulated oocytes, but there was a large
      number of degenerated and fragmented ovulated oocytes in the MTA- and MTP-treated
      groups. Treatment with MEL, MTA and MTP also resulted in lower plasma levels of
      estradiol-17 beta and progesterone.

PMID- 8748670
TI  - beta-CIT SPECT demonstrates blockade of 5HT-uptake sites by citalopram in the
      human brain in vivo.
AB  - The cocaine analogue 2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane (beta-CIT)
      is a potent ligand for both dopamine- and serotonin uptake sites which in its
      123I labeled form can be used for single photon emission computerized tomography
      (SPECT). It was demonstrated previously by SPECT-studies in non-human primates
      that 123I-beta-CIT binds to dopamine transporters in the striatum and to
      serotonin transporters in hypothalamus and midbrain. The aim of the present study
      was to compare 123I-beta-CIT binding in the brain stem of normal controls and a
      group of subjects under treatment with the selective serotonin reuptake inhibitor
      (SSRI) citalopram. 123I-beta-CIT-SPECT was performed in 12 depressed patients
      under 20 mg (n = 5), 40 mg (n = 6) and 60 mg (n = 1) citalopram daily, in one
      untreated depressed patient and in 11 controls at regular time intervals up till
      24 hours p.inj. A highly significant reduction of beta-CIT binding was found in
      an area including mesial thalamus, hypothalamus, midbrain and pons in patients
      under citalopram compared to controls (44.1 +/- 14.4 vs. 82.3 +/- 18.6cpm's/mCi x
      kg body weight; specific binding 4 hrs p.inj.; p = 0.0001). No differences were
      seen between the high and low dose group and no changes were found in the
      striatum. 123I-beta-CIT binding in the brain stem and striatum in one untreated
      depressed patient fell within the range of control values. To our knowledge this
      is the first report directly demonstrating the effect of a selective serotonin
      uptake inhibitor in the brain in humans in vivo. SPECT measurements of serotonin
      uptake sites in patients with depression and other psychiatric disorders might
      provide better insights into the pathophysiology of these disorders and into
      mechanisms of drug action.

PMID- 8748671
TI  - Delayed changes in neural visinin-like calcium-binding protein gene expression
      caused by acute phencyclidine administration.
AB  - Phencyclidine (PCP) induces a psychotomimetic state that closely resembles
      schizophrenia, and PCP-treated animals can serve as a model for schizophrenia.
      The effects of PCP on the gene expression of NVP-1, a novel Ca(2+)-binding
      protein, were studied in rats. After 24 hours, the NVP-1 mRNA level in the
      nucleus accumbens showed a significant decrease of 42%. This result suggests that
      alterations in Ca(2+)-binding protein may be involved in the pathology of PCP
      induced psychosis and, presumably, schizophrenia.

PMID- 8748672
TI  - Nitrite, nitrate and cGMP in the cerebrospinal fluid in degenerative neurologic
      diseases.
AB  - To investigate whether nitric oxide (NO) plays a role in degenerative neurologic
      disease (DND), we measured nitrite, nitrate and cyclic GMP in cerebrospinal fluid
      (CSF) samples from patients with Parkinson's disease (PD), spinocerebellar ataxia
      (SCA) and amyotrophic lateral sclerosis (ALS). We found no significant change in
      CSF nitrite, nitrate or cyclic GMP in patients with any DND compared with control
      values. These results suggest that NO production is preserved in PD, SCA and ALS.

PMID- 8748673
TI  - Antidepressant-like effects of SR 57227A, a 5-HT3 receptor agonist, in rodents.
AB  - We have investigated the effect of SR 57227A, a selective 5-HT3 receptor agonist
      which crosses the blood brain barrier, on three rodent models in which
      antidepressants are active. In the forced swimming test, SR 57227A dose
      dependently reduced the duration of immobility in mice and rats after i.p.
      administration. (ED50 = 14.2 mg/kg i.p. in mice, and 7.6 mg/kg i.p. in rats.) The
      compound was also active in both species after oral administration. In a time
      course study in mice, SR 57227A (20 mg/kg p.o.) produced a significant effect
      lasting 6 h. SR 57227A (1 and 3 mg/kg i.p.) reduced the elevation of the escape
      failures in the learned helplessness model in rats by 50-60% on the last two days
      of the avoidance task, and reduced isolation-induced aggressivity in mice by 50
      to 85%, an effect which was antagonised by zacopride (1 mg/kg i.p.). These
      results suggest that the stimulation of 5-HT3 receptors can produce
      antidepressant-like effects in behavioral tests in rodents.

PMID- 8748674
TI  - Pyridoxine effect on synthesis rate of serotonin in the monkey brain measured
      with positron emission tomography.
AB  - The influence of the co-factor pyridoxine, vitamin B6, on the activity of
      aromatic amino acid decarboxylase enzyme was studied by positron emission
      tomography, PET in the brain of the Rhesus monkey using the precursor for
      serotonin synthesis 5-hydroxy-L-tryptophan (5-HTP) radiolabelled with 11C in the
      beta-position. The rate constant for the formation of serotonin in the corpus
      striatum was calculated using a two tissue compartment model with reference area
      in the brain. In baseline investigations, the mean rate constants (+/-S.D:) for
      selective utilization of [11C]5-HTP to form [11C]serotonin in the corpus striatum
      was 0.0080 +/- 0.0011 min(-1). Pretreatment with intravenous pyridoxine
      hydrochloride 10 mg/kg bodyweight before doing a second PET study resulted in an
      enhanced rate constant by a mean of 20%. The rate increase was statistically
      significant. The increase varied considerably in different monkeys from no effect
      to more than 60%. The effect of pyridoxine on aromatic amino acid decarboxylase
      activity supported a regulatory role of pyridoxine on the synthesis of
      neurotransmitter in vivo, and may be of importance in diseases with deficiencies
      in neurotransmitter function.

PMID- 8748675
TI  - Phencyclidine-induced increases in striatal neuron firing in behaving rats:
      reversal by haloperidol and clozapine.
AB  - Amphetamine and related drugs of abuse facilitate dopamine transmission in the
      striatum. This action is believed to underlie the increase in firing of striatal
      motor-related neurons after amphetamine administration in behaving rats. The
      present study extended this electrophysiological investigation to phencyclidine
      (PCP), a nonamphetamine psychomotor stimulant that acts primarily as a
      noncompetitive antagonist of N-methyl-D-aspartate (NMDA) glutamate receptors.
      Like amphetamine, PCP (1.0, 2.5, or 5.0 mg/kg) increased the activity of striatal
      motor-related neurons concomitant with behavioral activation. These effects were
      blocked by subsequent administration of either 1.0 mg/kg haloperidol or 20.0
      mg/kg clozapine, typical and atypical neuroleptics, respectively. Dizocilpine (MK
      801), another noncompetitive NMDA antagonist, mimicked the effect of PCP.
      Collectively, these results indicate that amphetamine and NMDA antagonists exert
      comparable effects on striatal motor-related neurons, suggesting that the
      response of these cells to psychomotor stimulants is regulated by a dopaminergic
      glutamatergic influence.

PMID- 8748676
TI  - Effects of tacrine upon murine neuroblastoma cells.
AB  - Tacrine [9-amino-1,2,3,4-tetrahydroacridine] (THA), a potent
      acetylcholinesterasic inhibitor, is utilized in the pharmacological treatment of
      Alzheimer's disease (Birne and Arie, 1994). Cytopharmacology of THA is still
      largely to be discovered. In the present paper we report some effects produced by
      THA on murine neuroblastoma cells (N2A) used as an experimental model. N2A cells
      treated with THA at low concentration (1 mu M) showed a reduced cell's mitosis
      and a remarkable reduction of protein synthesis. Eventually, a marked reduction
      on the phosphorylation of proteins associated to neurofilaments 200 kD, is
      observed using specific antibody.

PMID- 8748677
TI  - Neurotensin peptides antagonistically regulate postsynaptic dopamine D2 receptors
      in rat nucleus accumbens: a receptor binding and microdialysis study.
AB  - An in vitro receptor binding and in vivo microdialysis study was performed to
      further investigate the modulation of dopamine (DA) D2 receptors by neurotensin
      (NT) peptides. Saturation experiments with the D2 agonist [3H]NPA (N
      propylnorapomorphine) showed that 10 nM of NT, 10 nM of neuromedin N (NN) and 1
      nM of the C-terminal NT-(8-13) fragment significantly increased the KD values by
      125%, 181%, and 194%, respectively without significantly affecting the Bmax value
      of the [3H]NPA binding sites in coronal sections of rat ventral forebrain mainly
      containing the nucleus accumbens (Acb) and the olfactory tubercle. In line with
      the previous findings that NT can increase GABA release in the Acb and that NT
      receptors are not found on DA terminals in this brain region, the present in vivo
      microdialysis study demonstrated that local perfusion of NT (1 nM) counteracted
      the D2 agonist pergolide (2 mu M) induced inhibition of GABA, but not of DA
      release in the rat Acb. This result indicates that NT counteracts the D2 agonist
      induced inhibition of GABA release in the rat Acb, via an antagonistic
      postsynaptic NT/D2 receptor interaction as also suggested by the inhibitory
      regulation of D2 receptor affinity in the Acb by the NT peptides demonstrated in
      the present receptor binding experiments. Thus, the neuroleptic and potential
      antipsychotic profile of the NT peptides may involve an antagonistic NT/D2
      receptor regulation in the ventral striatum.

PMID- 8748678
TI  - Effects of monoamine uptake inhibitors given early postnatally on monoamines in
      the brain stem, caudate/putamen and cortex, and on dopamine D1 and D2 receptors
      in the caudate/putamen.
AB  - Rats were treated with desipramine 5 mg/kg, nomifensine 10 mg/kg, zimelidine 25
      mg/kg or with 0.9% sodium chloride once a day during the second and third weeks
      after birth, and brain stem, caudate/putamen and cortical monoamines, and
      caudate/putamen dopamine D1 (3[H]SCH 23390) and D2 (3[H]spiroperidol) receptor
      binding were measured when rats were at two months of age. In the brain stem, the
      concentration of 3-methoxy-4-hydroxy-phenyl glycol was increased in nomifensine
      rats and the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was
      increased in zimelidine rats. In the caudate/putamen, the concentrations of 3,4
      dihydroxyphenylacetic acid and homovanillic acid and the ratio of homovanillic
      acid to dopamine were increased in desipramine rats; neither 3[H]SCH 23390 nor
      3[H]spiroperidol binding were affected by any of the three monoamine uptake
      inhibiting antidepressants studied. In the cortex, the ratio of 5
      hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in desipramine and
      zimelidine rats. The findings suggest that desipramine but not nomifensine
      increases the metabolism of dopamine in the caudate/putamen and nomifensine but
      not desipramine increases the metabolism of norepinephrine in the brain stem, and
      furthermore that the metabolism of serotonin is affected by desipramine as well
      as by zimelidine. It is possible that also treatment of women with these drugs
      during late pregnancy causes long-lasting changes in the brain of human fetus.

PMID- 8748679
TI  - Evidence for prolonged recovery of dopaminergic transmission after detoxification
      in alcoholics with poor treatment outcome.
AB  - It has been hypothesized that dysfunction of dopaminergic neurotransmission is
      involved in the pathogenesis of alcohol addiction. Therefore, peripheral dopamine
      levels, sensitivity of central dopamine receptors (apomorphine-induced Growth
      Hormone (GH) secretion), and the inhibitory efficacy of G-proteins on adenylyl
      cyclase activity (as an indicator for dopamine D2-receptor coupled second
      messenger mechanisms) were measured in 45 alcohol-dependent patients before and
      after detoxification and in 10 healthy controls. The time needed to adjust to
      abstinence conditions differed between patients with good and poor treatment
      outcome. In subsequent abstainers, effects of alcohol withdrawal were already
      found during the first 24 hours of abstinence (normalisation of GH response,
      increases in dopamine levels and the inhibitory efficacy of G-proteins). During
      the next 7 days of abstinence, no more significant changes were observed in the
      assessed variables. In subsequent relapsers, no significant effect of acute
      ethanol withdrawal on the same measures was found. However, at day 8 of
      abstinence, increases in apomorphine-induced GH secretion (towards
      normalisation), in dopamine plasma levels, and in the inhibitory efficacy of G
      proteins (towards above-normal levels) were observed. This retarded adjustment of
      dopaminergic signal transduction seems to reflect the relapse risk of treatment
      nonresponders.

PMID- 8748680
TI  - Sulfamethoxazole-trimethoprim double-blind, placebo-controlled, crossover trial
      in Machado-Joseph disease: sulfamethoxazole-trimethoprim increases cerebrospinal
      fluid level of biopterin.
AB  - We performed a double-blind, placebo-controlled, crossover trial of
      sulfamethoxazole-trimethoprim (S-T) in 8 patients with Machado-Joseph disease
      (MJD), and measured the blood and cerebrospinal fluid levels of biopterins,
      biogenic amines or metabolites, and folate. The clinical results were as follows;
      mild improvements of hyperreflexia of knee jerks and of rigospasticity of the
      legs during S-T treatment period. In addition, S-T significantly reduced the
      times of 8 motor activities on the timed tests. The biochemical results showed
      that basal levels of all biopterins and homovanillic acid in the cerebrospinal
      fluid (CSF) were reduced to less than half the levels of those of controls with
      other neurological diseases. After S-T treatment, total and oxidized form of
      biopterins in the CSF increased significantly. Therefore, S-T may be effective to
      neurologic deficits through its mechanism of increasing the level of brain
      biopterins.

PMID- 8748681
TI  - Comparative biotransformation of hexachlorobenzene and hexafluorobenzene in
      relation to the induction of porphyria.
AB  - The porphyrinogenic action of hexafluorobenzene was investigated and compared to
      that of hexachlorobenzene. Metabolite patterns in the urine of exposed rats were
      determined to quantify the extent of metabolism through cytochrome P450 catalysed
      oxidation and glutathione conjugation. Results obtained demonstrate an almost
      similar extent of formation of phenolic metabolites. However, in the urine of
      hexachlorobenzene exposed rats significantly higher levels of the N-acetyl-S
      (pentahalophenyl)cysteine were observed than in the urine of hexafluorobenzene
      exposed rats. Hexafluorobenzene exposure did not result in induction of
      porphyria, whereas exposure to hexachlorobenzene did result in significantly
      elevated levels of urinary as well as liver porphyrins. Together these results
      indicate that if the reactive intermediate is indeed formed in the cytochrome
      P450 catalysed initial oxidative dehalogenation, the extent of its formation as
      well as its subsequent reactivity and reaction pathways vary with the type of the
      halogen substituents. Furthermore, the results seem to indicate that the extent
      of metabolism of hexahalogenated benzenes into urinary metabolites resulting from
      glutathione conjugation is a better indication of their porphyrinogenic action
      than their extent of metabolism to phenolic metabolites. Two explanations for
      this observation are presented.

PMID- 8748682
TI  - Mechanism of protection of lobenzarit against paracetamol-induced toxicity in rat
      hepatocytes.
AB  - The protective effects of lobenzarit, an antioxidative agent and antirheumatic
      drug, on the cytotoxicity of paracetamol in rat hepatocytes were studied, as well
      as the inhibitory effects of lobenzarit on cytochrome P-450s and glutathione S
      transferases (GSTs) in rat liver. Paracetamol was selected as a model toxin,
      since it is known to be bioactivated by specific cytochrome P-450s presumably to
      N-acetyl-p-benzoquinoneimine, a reactive metabolite which upon overdosage of
      paracetamol causes protein and non-protein thiol depletion, lipid peroxidation
      and cytotoxicity measurable as LDH leakage. At concentrations of lobenzarit of
      0.2 and 0.3 mM, added 30 min before paracetamol, the drug prevented paracetamol
      induced leakage of lactate dehydrogenase (LDH) almost completely and lipid
      peroxidation (LPO) and depletion of glutathione (GSH) substantially and also the
      formation of the 3-glutathionyl conjugate of paracetamol. However, at a
      concentration of 0.05 mM Lobenzarit did not protect anymore against the
      paracetamol toxicity, When added to the hepatocytes 1 h and 2 h before
      paracetamol, 0.05 and 0.2 and 0.3 mM concentrations of lobenzarit did not protect
      against the cytotoxicity induced by paracetamol either. Lobenzarit did not
      inhibit cytochromes P-450 1A1/1A2, 2B1/2B2 and 2E1 which were measured as
      ethoxyresorufin O-deethylation (EROD) activity in beta-naphthoflavone-induced rat
      liver microsomes, as pentoxyresorufin de-pentylation (PROD) activity in
      phenobarbital-induced microsomes and as p-nitrophenol hydroxylation (PNPH)
      activity in pyrazol-induced microsomes. Lobenzarit did not show inhibition of
      glutathione S-transferase (GST) activity towards 1-chloro-2,4-dinitrobenzene
      (CDNB) in cytosol from liver of rats treated with phenobarbital, pyrazol and beta
      naphthoflavone either. It is concluded that the cytoprotective effect of
      lobenzarit is most likely due to its antioxidant effects and/or to its ability to
      stimulate GSH reductase.

PMID- 8748683
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced anorexia and wasting syndrome in
      rats: aggravation after ventromedial hypothalamic lesion.
AB  - Long-term regulation of body weight and food intake were studied after rats were
      subjected to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which causes hypophagia
      and body weight loss, and to ventromedial hypothalamic lesion, which causes
      hyperphagia, metabolic changes and obesity. These two factors appeared to have an
      interaction, as ventromedial hypothalamic lesion initially aggravated the effects
      of TCDD on body weight and food intake. This was seen in both TCDD-resistant and
      TCDD-susceptible rat strains. In contrast, if TCDD was given several weeks before
      the lesion and body weight had stabilized to a low level, no aggravation was
      seen, but TCDD completely blocked the effects of ventromedial hypothalamic
      lesion. Thus, TCDD seems to affect the same regulation chain that is involved in
      the lesioning of the ventromedial hypothalamus. TCDD might serve as a tool in
      studying different mechanisms of long-term food intake and body weight
      regulation.

PMID- 8748684
TI  - Studies on the neurotoxicity of 6,7-dihydroxy-1-methyl-1,2,3,4
      tetrahydroisoquinoline (salsolinol) in SH-SY5Y cells.
AB  - We have studied the hypothesis that 6,7-dihydroxy-1-methyl-1,2,3,4
      tetrahydroisoquinoline (salsolinol) is neurotoxic. Salsolinol induced a
      significant time and dose related inhibition of 3[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide; thiazoyl blue (MTT) reduction, and increased lactate
      dehydrogenase release (LDH) release from human SH-SY5Y neuroblastoma cells, at
      concentrations within the range of 1-methyl-4-phenylpyridinium (MPP+)
      cytotoxicity, in vitro. Cytotoxicity was not inhibited by the addition of
      antioxidants, monoamine oxidase inhibitors or imipramine. In confluent
      monolayers, salsolinol stimulated catecholamine uptake with EC50 values of 17 muM
      and 11 muM, for noradrenaline and dopamine, respectively. Conversely, at
      concentrations above 100 muM, salsolinol inhibited the uptake of noradrenaline
      and dopamine, with IC50 values of 411 muM and 379 muM, respectively. The
      inhibition of catecholamine uptake corresponded to the increase displacement of
      [3H]nisoxetine from the uptake 1 site by salsolinol, as the Ki (353 muM) for
      displacement was similar to the IC50 (411 and 379 muM) for uptake. Salsolinol
      stimulated catecholamine uptake does not involve the uptake recognition site, or
      elevation of cAMP, cGMP, or inhibition of protein kinase C. Salsolinol also
      inhibited both carbachol (1 mM) and K+ (100 mM, Na+ adjusted) evoked released of
      noradrenaline from SH-SY5Y cells, with IC50 values of 500 muM and 120 muM,
      respectively. In conclusion, salsolinol appears to be cytotoxic to SH-SY5Y cells,
      via a mechanism that does not require uptake 1, bioactivation by monoamine
      oxidase, or membrane based free radical damage. The effects of salsolinol on
      catecholamine uptake, and the mechanism of toxicity require further
      investigation.

PMID- 8748685
TI  - Lipopolysaccharide-induced hepatotoxicity is inhibited by the antioxidant
      melatonin.
AB  - Oxidative damage to the liver of lipopolysaccharide-treated rats was evaluated
      using four parameters: level of lipid peroxidation, changes in total GSH and GSSG
      concentrations and hepatic morphology. Bacterial lipopolysaccharide (10 mg/kg
      b.w.) was injected i.p. either at 6, 16 or 24 h before animals were killed.
      Lipopolysaccharide increased lipid peroxidation most dramatically when it is
      injected 6 h before killing. Hepatic total GSH increased after lipopolysaccharide
      in a time-dependent manner. The highest level of GSSG and largest GSSG/total GSH
      ratio were also observed in the group of animals injected with lipopolysaccharide
      6 h before tissue collection. In a second study, lipopolysaccharide was injected
      6 h before the animals were killed, with or without 1 mg/kg b.w. melatonin.
      Melatonin totally abolished lipopolysaccharide-induced increase in lipid
      peroxidation, exaggerated the rise in total GSH and reversed the increase in GSSG
      concentration. The liver showed obvious histological degenerative changes after
      lipopolysaccharide, effects that were counteracted by melatonin administration.
      The protection conferred by melatonin is presumably due to its antioxidant
      activity.

PMID- 8748686
TI  - Down-regulation of hepatic peripheral-type benzodiazepine receptors caused by
      acute lead intoxication.
AB  - In the present study we investigated the influence of acute lead poisoning upon
      the expression of benzodiazepine receptors. In addition, we examined if
      administration of PK 11195, an isoquinoline carboxamide derivative, to lead
      poisoned rats could modulate the changes in receptor binding properties achieved
      by lead alone. Lead poisoning was ascertained by determination of urine delta
      aminolevulinic acid levels and lead levels in rat livers. Scatchard analysis of
      saturation curves of [3H]PK 11195 binding to liver membranes of rats treated with
      lead alone or with both lead and PK 11195 showed and approximately two-fold
      decrease in receptor density in comparison with control groups. Peripheral
      benzodiazepine receptor density in kidneys and adrenals of poisoned rats was not
      changed by lead intoxication per se or by coadministration of PK 11195. Scatchard
      analysis of saturation curves of [3H]Ro 15-1788 binding in rat cerebral cortex
      tissue showed no difference in the receptor density between the various groups.
      The Kd values of all organs were in the nanomolar range (1-4 nM). We conclude
      that PK 11195 is not a protective agent of hepatic peripheral benzodiazepine
      receptors in lead intoxication. Moreover, it causes over-accumulation of lead in
      hepatocytes in an unknown mechanism of action.

PMID- 8748687
TI  - Toxic equivalency factors do not predict the acute toxicities of dioxins in rats.
AB  - Risk evaluation of complex environmental mixtures of polychlorinated dibenzo-p
      dioxins and related halogenated aromatic hydrocarbons (polychlorinated
      dibenzofurans, azo- and azoxybenzenes, naphthalenes and some of the biphenyls) is
      currently carried out by measuring the concentration of each congener in the
      mixture and then multiplying every figure by its specific constant, toxic
      equivalency factor (TEF). All congeners are thought to produce highly similar
      effects albeit at different doses, and the TEFs are believed to represent the
      potencies of the congeners relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD), considered the most toxic derivative of this class of environmental
      contaminants. Here we compared the acute toxicities of TCDD, 1,2,3,7,8-penta-,
      1,2,3,4,7,8-hexa- and 1,2,3,4,6,7,8-heptachloro-dibenzo-p-dioxin in the most TCDD
      susceptible (Long-Evans Turku AB; L-E) and the most TCDD-resistant (Han/Wistar
      kuopio; H/W) rat strain. While L-E rats exhibited the expected rank order of
      sensitivities to the four dioxins, the higher chlorinated dioxins were more toxic
      than TCDD (in terms of acute lethality) to H/W rats, with the hexachlorodioxin
      showing the greatest potency. Even if the doses were adjusted according to the
      LD50 values, both biochemical and morphological effects elicited by the dioxins
      turned out to depend, often critically, on strain, congener or the interaction of
      these two determinants. These findings demonstrate that the dioxins have distinct
      profiles of acute toxicities and underscore the importance of response and test
      organism in defining the TEFs.

PMID- 8748688
TI  - A sex-related difference in the neurobehavioral and hepatic effects following
      chronic endosulfan treatment in rats.
AB  - The neurobehavioral and hepatic effects following chronic endosulfan
      administration were studied in adult male and female rats. The neurobehavioral
      effect was determined by testing spontaneous motor activity, motor coordination
      and learning and memory processes in rats of either sex, 30 days after treating
      the animal orally with endosulfan (3.0 and 6.0 mg/kg per day). Mortality
      occurring during the treatment and body weight gain at the termination of
      treatment were also recorded. Liver weight and liver and serum concentrations of
      glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and
      acetylcholinesterase were measured in order to determine the hepatotoxic effect
      of endosulfan. Body weight gain, motor coordination and acetylcholinesterase
      activity were unaltered in either sex. Learning and memory processes were
      impaired in both groups indistinguishably. Liver weight and liver and serum
      transaminases concentrations were increased more markedly in female than in male
      animals. A 30% mortality occurred in female group that received 6 mg/Kg of
      endosulfan. Endosulfan stimulated spontaneous motor activity more markedly in
      male than in female animals. These findings suggest that a sex-related difference
      seems to occur in the stimulation of spontaneous motor activity, liver injury and
      mortality that result from repeated exposure to sublethal doses of endosulfan in
      rats.

PMID- 8748689
TI  - Role of the paracrine liver endothelin system in the pathogenesis of CCl4-induced
      liver injury.
AB  - This study analyzed if the paracrine liver endothelin system participates in the
      pathogenesis of CCl4-induced hepatotoxicity. Wistar Kyoto rats were divided into
      four groups: a bosentan (mixed endothelin ETA and ETB receptor antagonist)
      treated group with CCl4 intoxication, a vehicle treated group with CCl4
      intoxication, a nontreated control group and a bosentan treated control group.
      Hepatotoxicity was assessed by determination of alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), lactate dehydrogenase (LDH) followed by
      histopathological examinations. Tissue endothelin-1 concentrations and expression
      of endothelin receptor subtypes were analyzed. The tissue levels of endothelin-1
      in the liver of rats with CCl4 intoxication were significantly higher than those
      in normal rats. Scatchard analysis revealed no differences in the density and
      binding constant of endothelin ETA and ETB receptor between rats with CCl4
      intoxication and controls. Bosentan treatment of rats undergoing CCl4 inhalation
      resulted in a significant protection against elevation of ALT, AST, LDH and
      bilirubin. Histopathological examination of live sections for necrotic, swollen
      and lipid-laden cells revealed findings that were in agreement with the serum
      enzyme data. In conclusion, this study showed that the paracrine endothelin
      system is involved in the pathogenesis of CCl4-induced hepatotoxicity and that
      the blockade of the stimulated liver endothelin systems reduces CCl4-induced
      liver injury.

PMID- 8748690
TI  - Role of lipoxygenase metabolites in platelet-activating factor- and antigen
      induced bronchial hyperresponsiveness and eosinophil infiltration.
AB  - The effect of a novel leuktriene B4 receptor antagonist N-[5[[8-(1-hydroxy-2-
      phenyl)ethyl]dibenzofuran-2yl]5-hydroxypentanoyl]pyrrolidine (PF 10042) has been
      evaluated in comparison with 2-[3(1-hydroxyhexyl)phenoxymethyl]quinoline
      hydrochloride (PF 5901), a specific inhibitor of the 5-lipoxygenase pathway of
      arachidonic acid metabolism, against platelet activating factor (PAF) and
      allergen induced bronchial hyperresponsiveness and pulmonary eosinophil
      infiltration in the guinea pig. PF 10042 significantly displaced radiolabelled
      [3H]leukotriene B4 from binding sites on human neutrophils with an EC50 of 3 muM.
      PF 10042 (100 mg/kg, i.p.) significantly inhibited PAF and allergen induced
      bronchial hyperresponsiveness without reducing the concomitant eosinophil
      infiltration, whereas PF 5901 (100 mg/kg, p.o.) significantly inhibited both PAF
      and allergen induced bronchial hyperresponsiveness and eosinophil infiltration.
      We suggest from these results that PAF and allergen induced bronchial
      hyperresponsiveness may be secondary to the release of leukotriene B4, but this
      lipoxygenase metabolite does not contribute significantly to the observed
      eosinophil infiltration.

PMID- 8748691
TI  - Vulnerability of mitochondrial complex I in PC12 cells exposed to manganese.
AB  - The present findings provide experimental evidence for the hypothesis that an
      impairment of mitochondrial function may be involved in manganese neurotoxicity.
      Specifically, the treatment of dopaminergic neuronal-derived cell line (PC12)
      with MnCl2 produced a significant inhibition of some mitochondrial complexes of
      the respiratory chain, while in the glial-derived cell line (C6) this effect was
      not observed. In PC12 the decrease in complex I activity was more pronounce than
      in other mitochondrial complexes. However treatment of cells with ZnSO4 exerted
      no significant variations in enzymatic activities. A direct exposure of
      mitochondrial fraction to MnCl2 reduced enzymatic activities of mitochondria in
      both cell lines adding further support to the proposed theory that the different
      sensitivity of the cells to manganese may be explained by a difference in uptake
      or intracellular storage. These data indicate that manganese neurotoxicity could
      be the result of a direct effect just on complex I activity or due to a secondary
      effect of oxidative stress induced by an excess of this transition metal.

PMID- 8748692
TI  - Defective expression of cytochrome P450 proteins in the liver of the genetically
      obese Zucker rat.
AB  - The hepatic expression of xenobiotic-metabolising cytochrome P450 isoforms in the
      genetically obese Zucker rat, a model of obesity, was compared to that of its
      lean littermate. Cytochrome P450 (CYP) levels were determined using diagnostic
      substrates and/or immunologically in Western blot analyses. When compared with
      the lean Zucker rat, the obese animal exhibited hyperglycaemia,
      hypercholesterolaemia, marked hyperinsulinaemia and hypertriglyceridaemia but was
      normoketonaemic. CYP3A and CYP1A2 levels were higher in the obese Zucker rat when
      compared with the lean littermate but, in contrast, a protein recognised by human
      CYP2D6 and, to a lesser extent, CYP2C11 levels were lower. Pretreatment with
      acetone, dexamethasone and clofibrate resulted in enhanced p-nitrophenol
      hydroxylase (CYP2E), erythromycin N-demethylase (CYP3A) and lauric acid
      hydroxylase (CYP4A) activities respectively in the liver of the lean Zucker rat
      but, in contrast, the obese Zucker rat was refractive to such treatment;
      similarly, hepatic apoprotein levels of the CYP2E and CYP4A subfamilies were
      increased markedly only in the lean Zucker rat. It is concluded that CYP2E, CYP3A
      and CYP4A subfamilies are poorly expressed in the obese Zucker rat, and this rat
      strain may serve as a good model for elucidating the molecular mechanisms of
      induction of these cytochrome P450 proteins.

PMID- 8748693
TI  - Calcitonin gene-related peptide and nitric oxide are involved in ultraviolet
      radiation-induced immunosuppression.
AB  - Contact hypersensitivity responsiveness to dinitrofluorobenzene is depressed in
      mice that are sensitized through skin sites exposed to ultraviolet (UV)
      radiation. Local impairment of contact hypersensitivity by UV has been associated
      with a reduction in antigen-presenting cell activity within UV-irradiated skin
      sites marked by a decrease in the density of Ia-positive epidermal Langerhans
      cells. Our recent studies have demonstrated that neurogenic mediators (e.g.
      calcitonin gene-related peptide (CGRP) and nitric oxide (NO) contribute to
      cutaneous inflammation following exposure of rats to high-dose UV radiation.
      Since CGRP and NO inhibit antigen presentation by dendritic cells in vitro, we
      have investigated the possible involvement of CGRP and NO in local
      immunosuppression in UV-irradiated rodents. Hindpaw skin of Sprague-Dawley rats
      and back skin of UV-susceptible C57BL/6 mice was exposed to acute UV radiation
      (2.0 J/cm2 and 0.5 J/cm2, respectively). Alterations in cutaneous CGRP content
      were analyzed by a specific radioimmunoassay (RIA). In separate experiments, the
      CGRP receptor antagonist CGRP-(8-37) (10-5 M) and the nitric oxide synthase
      inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (2 X 10-5 M) were topically
      applied to UV-exposed skin before induction of contact hypersensitivity with
      dinitrofluorobenzene. Finally, we examined the effects of UV irradiation and
      epicutaneous application of CGRP on Ia-positive Langerhans cells by
      immunohistochemical analysis of epidermal sheets. It was found that UV exposure
      lead to a decrease in skin CGRP levels starting already 2 h after irradiation and
      reaching a minimum (less than 40% of non-irradiated control skin) at 6-12 h.
      Contact hypersensitivity reactions were significantly suppressed by UV radiation
      in rat skin (by 51%) and murine skin (by 80%). Topical administration of both
      CGRP-(8-37) and L-NAME before sensitization restored the capacity to respond to
      haptens applied to UV-exposed skin. Both UV exposure and topical CGRP reduced the
      density of Ia-positive epidermal cells. Our data indicate that CGRP may be
      released from sensory neurons following cutaneous UV irradiation and that CGRP
      and NO contribute of UV-induced local immunosuppression. Moreover, topical
      administration of CGRP or its antagonist may be able to modulate epidermal
      Langerhans cell activity in vivo.

PMID- 8748694
TI  - Bronchoconstriction and airway hyperresponsiveness after ovalbumin inhalation in
      sensitized mice.
AB  - To investigate the mechanisms underlying airway hyperresponsiveness a murine
      model was developed with several important characteristics of human allergic
      asthma. Mice were intraperitoneally sensitized with ovalbumin and after 4 weeks
      challenge via an ovalbumin aerosol. After aerosol, lung function was evaluated
      with a non-invasive forced oscillation technique. The amount of mucosal exudation
      into the airway lumen and the presence of mast cell degranulation was determined.
      Tracheal responsiveness was measured at several time points after challenge. At
      these time points also bronchoalveolar lavage and histology were performed.
      Sensitization induced high antigen-specific IgE levels in serum. Inhalation of
      ovalbumin in sensitized mice induced an immediate but no late bronchoconstrictive
      response. During this immediate phase, respiratory resistance was increased
      (54%). Within the first hour after ovalbumin inhalation increased mucosal
      exudation and mast cell degranulation were observed. At 12 and 24 h after
      ovalbumin challenge, mice showed tracheal hyperresponsiveness (29% and 34%,
      respectively). However, no apparent inflammation was found in the lungs or
      bronchoalveolar lavage. From these results it can be concluded that
      hyperresponsiveness can develop via mechanisms independent of an inflammatory
      infiltrate. Since mast cell degranulation occurred after ovalbumin exposure, we
      hypothesize that mast cells are involved in the induction of airway
      hyperresponsiveness in this model.

PMID- 8748695
TI  - Evidence for the promotion of positive selection of thymocytes by Ah receptor
      agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a ligand for the arylhydrocarbon
      receptor (Ah receptor), abundant in the murine thymus. In the thymus
      immunocompetent T cells develop. Upon exposure of murine fetal thymi in organ
      cultures to TCDD the distribution of mature and immature thymocytes is skewed
      towards apparently mature, prospective cytotoxic cells of the CD4-CD8+T cell
      receptor+ phenotype. The normally abundant CD4+ CD8+ cells are decreased.
      Proliferation of the most immature thymocyte subpopulations is inhibited and
      maturation of thymocytes appears accelerated by TCDD. Eventually the thymocyte
      number is significantly decreased. Selective treatment of stroma cells showed
      them to be the primary target cells of TCDD action. Thymus stroma plays a pivotal
      role in thymocyte maturation and is indispensable for the selection of thymocytes
      bearing T cell receptors specific for foreign antigen in the context of self. We
      tested whether the effects of TCDD on thymocyte differentiation and maturation
      has further consequences for the selection processes by analysing (a) the
      repertoire of V beta genes used as a measure for negative selection and (b) the
      expression of CD69 and bcl-2 by thymocytes as a parameter of positive selection.
      Our data indicate that TCDD does not cause gross disturbance of negative
      selection but provide evidence for more cells auditioning for positive selection
      by TCDD exposure.

PMID- 8748696
TI  - Immunotoxic effects of prolonged dietary exposure of male rats to 2,3,7,8
      tetrachlorodibenzo-p-dioxin.
AB  - The effects of low level exposure of rats to 2,3,7,8-tetrachlorodibenzo-p- dioxin
      (TCDD) on their immune system was investigated Dietary administration to young
      adult male Leeds strain rats of a total dose of 3 micrograms/kg body weight of
      TCDD resulted in an exposure duration-dependent reduction of in vitro
      lipopolysaccharide-induced production of interleukin (IL)-1 in cultures of their
      splenic macrophages. A 30-day exposure produced approximately 30% suppression and
      180-day exposure produced approximately 52% suppression. This reduction did not
      negatively influence lipopolysaccharide- induced proliferation of B cells,
      instead an enhancement of B cell proliferation was observed after 30 days
      exposure. A 180 day exposure significantly suppressed the generation of IL-2 by
      either concanavalin A or phorbol myristate acetate/calcium ionophore stimulation,
      and reduced the lectin-induced proliferation of splenic T cells. The 30-day TCDD
      exposure showed no such immunotoxicity. TCDD at both exposure durations
      suppressed the expression of the alpha chain of the IL-2 receptor in concanavalin
      A-activated T cells, without affecting the CD4+/CD8+ ratio. The results suggest
      that exposure to a low dietary dose of TCDD suppresses the functions of several T
      cell subsets, some of the immunotoxic effects being produced early, while others
      require a longer exposure also down-regulates the IL-1 production function of
      macrophages. A common mechanism of TCDD immunotoxicity may be on the
      multifunctional signal transduction pathways downstream to the activation of
      protein kinase C and Ca2+ flux.

PMID- 8748697
TI  - Kinetics of nitric oxide synthase induction by Propionibacterium avidum and
      lipopolysaccharide.
AB  - Conditions for the induction of rat liver Ca2(+)-independent nitric oxide
      synthase were determined with killed Propionibacterium avidum, and compared with
      lipopolysaccharide endotoxin. Similar maximal induction was obtained
      intraperitoneally with the two types of inducers but killed Propionibacterium
      avidum gave a long-lasting induction while lipopolysaccharide displayed a rapid
      and short response. Moreover, the induction resulting from an intravenous
      administration of killed Propionibacterium avidum reached 60 times that of the
      control whereas lipopolysaccharide treatment induced a 24-fold stimulation only.
      It is noteworthy that with the first inducer the nitric oxide activity was stable
      with time whereas with the second one it dropped after 8 h. Whatever the route of
      administration of killed Propionibacterium avidum, some huge vacuolated Kupffer
      cells were found in the liver whose parenchyma was almost normal. Numerous
      monocytes, and unaltered Kupffer cells, were observed. Kupffer cells were
      identified to be responsible for the uptake of killed Propionibacterium avidum.

PMID- 8748698
TI  - Body temperature effect on methylenedioxymethamphetamine-induced acute decrease
      in tryptophan hydroxylase activity.
AB  - Brain tryptophan hydroxylase activity decreases within 15 min after a single
      administration of 3,4-methylenedioxymethamphetamine. In the present study, the
      effect of body temperature on this acute decrease of tryptophan hydroxylase
      activity was examined. 2 h after a single dose of 3,4
      methylenedioxymethamphetamine (20 mg/kg, s.c.), rats exhibited hyperthermia (38.7
      degrees C) or hypothermia (35.8 degrees C) when maintained at 25 degrees C or 6
      degrees C, respectively. The rectal temperature of control animals maintained at
      6 degrees C was not altered. Tryptophan hydroxylase activity measured in the
      hippocampus, striatum and frontal cortex of hyperthermic rats treated with 3,4
      methylenedioxymethamphetamine was decreased to 61%, 65%, and 71% of control
      levels, respectively, 2 h after drug treatment. However, in hypothermic rats, 3,4
      methylenedioxymethamphetamine had no effect on tryptophan hydroxylase activity in
      the hippocampus, striatum or frontal cortex. Non-drug-induced hyperthermia or
      hypothermia did not affect tryptophan hydroxylase activity. Since hypothermia may
      prevent the 3,4-methylenedioxymethamphetamine-induced decrease in tryptophan
      hydroxylase activity by reducing the formation of free radicals, the effect of a
      free radical scavenging agent, N-tert-butyl-alpha-phenylnitrone, was examined. N
      tert-butyl-alpha-phenylnitrone (200 mg/kg, i.p.) alone caused hypothermia but had
      no direct effect on tryptophan hydroxylase activity. Preadministration of N-tert
      butyl-alpha-phenylnitrone prevented 3,4-methylenedioxymethamphetamine from
      raising the temperature above normal and attenuated the drug-induced decrease in
      tryptophan hydroxylase activity in hippocampus, striatum and frontal cortex.
      However, when the rats treated with a combination of N-tert-butyl-alpha
      phenylnitrone and 3,4-methylenedioxymethamphetamine were maintained at
      hyperthermic conditions, N-tert-butyl-alpha-phenylnitrone had no protective
      effect. These results suggest that body temperature plays a prominent role in the
      3,4-methylenedioxymethamphetamine-induced acute decrease in tryptophan
      hydroxylase activity.

PMID- 8748699
TI  - A unique metabolism of inorganic arsenic in native Andean women.
AB  - The metabolism of inorganic arsenic (As) in native women in four Andean villages
      in north-western Argentina with elevated levels of As in the drinking water (2.5,
      14, 31, and 200 micrograms/1, respectively) has been investigated. Collected
      foods contained 9-427 micrograms As/kg wet weight, with the highest
      concentrations in soup. Total As concentrations in blood were markedly elevated
      (median 7.6 micrograms/1) only in the village with the highest concentration in
      the drinking water. Group median concentrations of metabolites of inorganic As
      (inorganic As, methylarsonic acid (MMA) and dimethylarsinic acid (DMA)) in the
      urine varied between 14 and 256 micrograms/1. Urinary concentrations of total As
      were only slightly higher (18-258 micrograms/1), indicating that inorganic As was
      the main form of As ingested. In contrast to all other populations studied so
      far, arsenic was excreted in the urine mainly as inorganic As and DMA. There was
      very little MMA in the urine (overall median 2.2%, range 0.0-11%), which should
      be compared to 10-20% of the urinary arsenic in all other populations studied.
      This may indicate the existence of genetic polymorphism in the control of the
      methyltransferase activity involved in the methylation of As. Furthermore, the
      percentage of DMA in the urine was significantly higher in the village with 200
      micrograms As/1 in the water, indicating an induction of the formation of DMA.
      Such an effect has not been observed in other studies on human subjects with
      elevated exposure to arsenic.

PMID- 8748700
TI  - Species-specific antagonism of Ah receptor action by 2,2',5,5'-tetrachloro- and
      2,2',3,3'4,4'-hexachlorobiphenyl.
AB  - Using recombinant cell lines showing Ah receptor-controlled expression of a
      luciferase reporter gene, the interaction of di-ortho-substitute polychlorinated
      biphenyls (PCBs) with Ah receptor agonists was studied. In the recombinant
      Hepa1c1c7 mouse hepatoma (H1L1.1c7) cells strong antagonistic interaction of
      2,2',5,5'-tetrachlorobiphenyl (PCB52) with luciferase expression induced by
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 3,3',4,4'-tetrachlorobiphenyl
      (PCB77) was observed, and similarly, between 2,2',3,3',4,4'-hexachlorobiphenyl
      (PCB128) and PCB77. Accordingly, PCB52 was found to inhibit ethoxyresorufin-O
      deethylase (EROD) induction by PCB77 in wild-type Hepa1c1c7 cells. In contrast,
      the antagonistic effect of PCB52 on TCDD-induced luciferase expression was only
      minor in recombinant guinea pig GPC16 colon adenocarcinoma (G16L1.1c8) and human
      HepG2 hepatoma (HG2L1.1c3) cells, and intermediate in recombinant H4IIE rat
      hepatoma (H4L1.1c4) cells. Gel retardation studies using a 32 P-labelled dioxin
      responsive element (DRE)-containing oligonucleotide, and ligand binding studies
      using [3H]TCDD, demonstrated that the species-specific antagonistic activity of
      PCB52 on Ah receptor-controlled luciferase expression is due to inhibition of Ah
      receptor ligand and DNA binding. We conclude, that Ah-mediated luciferase
      expression provides a useful tool to study the species specificity of Ah receptor
      (ant)agonists.

PMID- 8748702
TI  - Cardiovascular and respiratory changes following exposure to a synthetic toxin of
      Ptychodiscus brevis.
AB  - The present study demonstrated cardiorespiratory effects of a synthetic
      phosphorus-containing ichthyotoxic metabolite elaborated by the marine
      dinoflagellate Ptychodiscus brevis in anaesthetised cats. The metabolite at a
      dose of 0.25-1.5 mg/kg i.v., resulted in a dose-dependent fall in blood pressure
      and such vasodepressor effect was associated with bradycardia. There is initial
      respiratory apnoea followed by increased rate and depth of respiration
      (hyperapnoea) following the administration of the toxin. The hypotensive response
      was accompanied by a decrease in aortic baroreceptor activity. The ECG showed
      atrioventricular conduction block, arrhythmia and depression of S-T segment and T
      wave which indicated coronary insufficiency. Vasodepressive property of the toxin
      is presumably muscarinic in nature as atropine counteracted the vasodepression.

PMID- 8748701
TI  - Effects of ibuprofen on airway vascular response to cotton smoke injury.
AB  - We studied the effects of ibuprofen on bronchial blood flow and myocardial
      function after inhalation injury. Sheep (n = 12) were chronically instrumented
      with cardiovascular and pulmonary catheters. After 5 days of recovery period,
      baseline data were collected and the sheep were divided into two groups. Group S
      (n = 6) were insufflated with 48 breaths of cotton smoke; while group I (n = 6)
      were pretreated with ibuprofen (12mg/kg bolus followed by 3 mg/kg/h continuous
      infusion for 24 h) and challenged with the same dose of smoke. All the animals
      were studied for 24h. Bronchial blood flow increased significantly in both groups
      throughout the experimental period; while stroke volume as well as right and left
      ventricular stroke work indices of both groups were significantly decreased
      (group I worse than group S) in the second half of the experimental period. These
      data suggest that vasodilatory prostaglandins do not play a major role in the
      bronchial vascular response to smoke inhalation injury and myocardial depression
      seen post injury is worse in animals treated with ibuprofen.

PMID- 8748703
TI  - In vivo metabolites of N omega-nitro-L-arginine methyl ester: methanol and N
      omega-nitro-L-arginine.
AB  - N omega-nitro-L-arginine methyl ester (L-NAME) is commonly used as a selective
      inhibitor for in vivo studies of brain nitric oxide (NO) synthase. We aimed to
      study the fate of N omega-nitro-L-arginine [11C]methyl ester ([11C]L-NAME) using
      positron emission tomography in monkey and high performance liquid chromatography
      methods in dogs and rats. We found that [11C]L-NAME was rapidly (t1/2 = 2 min)
      metabolized into N omega-nitro-L-arginine (L-NA) and [11C]methanol which both had
      a slow rate of elimination. Although, in vivo, L-NAME administration leads to
      long-lasting NO synthase inhibition by L-NA, methanol which is a potent
      neurotoxin in primate may produce detrimental effects unrelated to NO synthase
      inhibition.

PMID- 8748704
TI  - Endothelin-1 mediates erythropoietin-stimulated glomerular endothelial cell
      dependent proliferation of mesangial cells.
AB  - These experiments were performed in an attempt to determine whether chronic
      stimulation of glomerular endothelial cells with recombinant human erythropoietin
      would alter mesangial cell proliferation. Glomerular endothelial cells in culture
      incubated with various concentrations of erythropoietin for up to 4 days
      exhibited dose-dependent endothelin-1 production. Moreover, the conditioned
      medium from erythropoietin-stimulated glomerular endothelial cells enhanced
      [3H]thymidine incorporation into mesangial cells. This enhancement was
      significantly attenuated in the presence of a endothelin A receptor antagonist,
      BQ-123. These results suggest that endothelin-1 mediates erythropoietin
      stimulated glomerular endothelial cell-dependent mesangial cell proliferation,
      resulting in the progression of glomerulonephritis.

PMID- 8748705
TI  - Synthesis and characterization of the human elastin W4 sequence.
AB  - Following the nomenclature of Sandberg, the W4 sequence of human elastin,
      [sequence: see text], has been synthesized by solid-phase methods and
      characterized by carbon-13 nuclear magnetic resonance, amino-acid analysis, mass
      spectra and elemental analysis. This sequence was then polymerized to greater
      than 50 kDa as determined by retention in 50 kDa molecular weight cut-off
      dialysis tubing. It has been successfully cross-linked by gamma-irradiation (20
      Mrad) to form an elastomeric matrix, designated as X20-poly(W4). Physical
      characterizations such as stress/strain, thermolelasticity, acid-base titration
      and inverse temperature transition studies have been carried out on this
      elastomer, which is homologous to the striking, poly(VPGVG), W4 sequence of
      bovine and porcine elastins. These results are compared with previous results on
      the polypentapeptide of elastin, (VPGVG)n, and it has been demonstrated that X20
      poly(W4) also is a dominantly entropic elastomer. Finally, the working model for
      the structure of this human elastin sequence was derived computationally using
      molecular mechanics and dynamics calculations. Thus the human W4 sequence appears
      to be structurally and functionally equivalent to the bovine and porcine W4
      sequences in spite of the less regular repeating pentamer sequence.

PMID- 8748706
TI  - The importance of the hydrophobic components of the binding energies in the
      interaction of omega-amino acid ligands with isolated kringle polypeptide domains
      of human plasminogen.
AB  - Three of the five kringle domains of human plasminogen (HPg), viz the first,
      fourth and fifth, exhibit significantly strong binding to omega-amino acids, such
      as epsilon-aminocaproic acid (EACA) and transaminomethylcyclohexane-1-carboxylic
      acid (AMCHA). In all cases, ligand stabilization is due to ion dipole attractions
      of its charged groups with polypeptide side chains, as well as hydrophobic
      clustering of the ligand methylene groups with appropriate hydrophobic residues
      within the kringle domain. In order to estimate the significance of the
      hydrophobic components of ligand stabilization, we have sought a more detailed
      description of these binding interactions. The standard thermodynamic binding
      parameters, delta G degrees, delta H degrees and delta S degrees, for association
      of EACA and AMCHA with isolated recombinant kringle regions of HPg have been
      determined at several temperatures to evaluate the changes in standard heat
      capacities (delta C degrees p) accompanying these interactions. In each case, the
      delta C degrees p values of binding were negative and in the range -36 to -91 cal
      mol -1 K -1, reflective of the importance of the hydrophobic components of the
      binding process and their probable effects on surrounding water structure.

PMID- 8748707
TI  - Synthesis of a metal binding protein designed on the alpha/beta scaffold of
      charybdotoxin.
AB  - The alpha/beta scaffold of the scorpion toxin charybdotoxin has been used for the
      engineering of a metal binding site. Nine substitutions, including three
      histidines as metal ligands, have been introduced into the original toxin
      sequence. The newly designed sequence, 37 amino acids long, has been assembled by
      solid-phase synthesis and HBTU (2-(1H-benzotriazol-1-yl)-1,1,3,3
      tetramethyluronium hexafluorophosphate) coupling of Fmoc-protected amino acids.
      Formation of the three disulfide bonds occurred efficiently and rapidly in the
      presence of glutathione, and this post-synthesis modification has facilitated the
      purification task enormously. The process of synthesis and purification was
      performed in less than a week with an overall 10.2% yield. Circular dichroism
      analysis showed that the newly designed protein is folded in a alpha/beta
      structure, similarly to the parent toxin. Electronic absorption spectroscopy,
      circular dichroism and gel filtration experiments have been used to show that
      Cu2+ and Zn2+ ions bind with high affinity to the newly engineered protein. These
      results demonstrate that the alpha/beta fold, common to all scorpion toxins, is a
      very versatile basic structure, tolerant for substitutions and able to present
      new sequences in a predetermined conformation. The chemical approach is shown to
      be effective, rapid and practical for the production of novel designed small
      proteins.

PMID- 8748708
TI  - Design of 16-residue peptides possessing antimicrobial and hemolytic activities
      or only antimicrobial activity from an inactive peptide.
AB  - We have explored the possibility of generating peptides having antimicrobial and
      hemolytic activities or only antimicrobial activity, from a 16-residue peptide,
      GFFALIPKIISSPLFK, corresponding to the N-terminal region of the toxin pardaxin.
      This peptide does not exibit these activities, although it can permeabilize model
      membranes. Peptides were synthesized wherein either A4 or P7 were substituted by
      K and S11 replaced by K. Peptides in which P7 and S11 were replaced with K, (AK)
      and A4 and S11 replaced with K and A instead of P at position 7, (KA) showed
      potent antimicrobial and hemolytic activities. However, the peptide where S11 and
      A4 were replaced with K, (KP) showed pronounced antimicrobial activity with very
      weak hemolytic activity. Circular dichroism studies indicated that peptides AK
      and KA had a strong propensity to occur in a helical conformation, whereas KP did
      not. Peptides AK and KA were very effective in permeabilizing model membranes,
      whereas KP was relatively ineffective. Our studies thus suggest the requirements
      for a peptide to have only antimicrobial activity and also that selectivity in
      activity can be rationalized on the basis of biophysical principles. Thus, by
      judicious positioning of amino acids, especially positively charged ones, it
      should be possible to generate biologically active peptides without taking
      recourse to a combinatorial approach.

PMID- 8748710
TI  - A model of the active site of dipeptidyl peptidase IV predicted by comparative
      molecular field analysis and molecular modelling simulations.
AB  - A molecular model of the active site of the serine protease dipeptidyl peptidase
      IV (DPP IV or CD26) has been developed on the basis of comparative molecular
      field analysis (CoMFA) of competitive inhibitors and by force field calculations.
      By application of CoMFA experimentally obtained inhibition constants Ki have been
      successfully predicted. The resulting steric and electrostatic coefficients of
      CoMFA were used for the development of the molecular model. The main assumptions
      of the model are the recognition of substrates or inhibitors by the side chains
      of a tyrosine (S1-position) and a tryptophan residue (S2-position). The model
      helps us to understand a multitude of experimental data regarding the substrate
      specificity of this enzyme as well as results obtained by genetic engineering
      experiments by other authors. General conclusions concerning a new family of
      serine proteases are drawn and discussed.

PMID- 8748709
TI  - Crystal and molecular structure of Boc-Phe-Val-OMe; comparison of the peptide
      conformation with its dehydro analogue.
AB  - The crystal structure of the peptide Boc-Phe-Val-OMe determined by X-ray
      diffraction methods is reported in this paper. The crystals grown from aqueous
      methanol are orthorhombic, space group P2(1)2(1)2(1),a = 11.843(2), b =
      21.493(4), c = 26.676(4) A3 and V = 6790 A3. Data were collected on a CAD4
      diffractometer using MoK alpha radiation (lambda = 0.7107 A) up to Bragg angle
      theta = 26 degrees. The structure was solved by direct methods and refined by a
      least-squares procedure to an R value of 6.8% for 3288 observed reflections.
      There are three crystal-lographically independent peptide molecules in the
      asymmetric unit. All the three molecules exhibit extended conformation. The
      sidechain of the Val2 residue shows two different conformations. The conformation
      of the peptide Boc-Phe-Val-OMe is compared with the conformation of Ac-delta Phe
      Val-OH. It is observed that while Boc-Phe-Val-OMe exhibits an extended
      conformation, Ac-delta Phe-Val-OH shows a folded conformation. The results of
      this comparison highlight the conformation constraining property of the delta Phe
      residue. Interestingly, even though Boc-Phe-Val-OMe and Ac-delta Phe-Val-OH are
      conformationally different, they exhibit similar packing patterns in the solid
      state.

PMID- 8748711
TI  - Isolation and characterization of two distinct lectins with antiproliferative
      activity from the cultured mycelium of the edible mushroom Tricholoma mongolicum.
AB  - Two lectins, TML-1 and TML-2, were isolated from Tricholoma mongolicum by ion
      exchange chromatography and gel filtration. They are dimers with molecular weight
      near 37000. The hemagglutinating activities of TML-1 and TML-2 are sensitive to
      lactose inhibition and are stable between 10 and 80 degrees C. They exhibit
      antiproliferative activities against mouse monocyte-macrophage PU5-1.8 cells and
      mouse mastocytoma P815 cells in vitro. The two lectins differ in the content of
      proline and tyrosine residues. Both are non-glycoproteins and have hydroxyproline
      residues.

PMID- 8748712
TI  - Proposals for the angiotensin II receptor-bound conformation by comparative
      computer modeling of AII and cyclic analogs.
AB  - A conformational search using high-temperature molecular dynamics on angiotensin
      II(AII) and on two cyclic S-S bridged analogs, namely [Hcy3,5]AII and
      [Cys3,5]AII, in conjunction with a cluster analysis based on the similarities of
      the three-dimensional patterns of the binding and activation elements, had led to
      putative AII receptor-bound conformations. These conformations are characterized
      by a compact folded shape of the peptide backbone, and by particular relative
      positions of the four pharmacophore groups, namely the aromatic moieties of the
      Tyr4, His6 and Phe8 residues, and the C-terminal carboxyl group. This compact
      folded shape, arising from attractive electrostatic interactions between the
      desolvated N- and C-terminal groups, is similar to the crystallographically
      determined conformation of AII bound to the antibody Fab receptor.

PMID- 8748713
TI  - Structural effects of the selective reduction of amide carbonyl groups in motilin
      1-12 as determined by nuclear magnetic resonance.
AB  - Motilin is a 22-residue peptide stimulating stomach and intestinal motility. The
      motilin 1-12 fragment displays biological effects similar to the native peptide.
      Selective reduction of the amide carbonyl groups to form CH2NH analogs leads to a
      significant reduction in activity for the first two N-terminal positions and to a
      complete loss of activity for all other positions. The structures of motilin 1-12
      and ten reduced analogs were investigated using the temperature dependence of the
      amide NH chemical shifts. In all the analogs, the structure of the N-terminal
      region (residues 1-5) was different from the structure of motilin 1-12, which is
      characterized by hydrogen bonding between Phe1 and Ile4. The structure of the C
      terminal region of analogs was similar to the structure of motilin 1-12 for the
      first two reduction positions only (1-2 and 2-3), indicating that the C-terminal
      portion of motilin 1-12 is more critical for biological activity. Complete
      structural characterizations of motilin 1-12, [CH2NH]1-2, and [CH2NH]4-5-motilin
      1-12 were performed by two-dimensional NMR spectroscopy and molecular modeling.
      The structural features observed confirm the differences based on the temperature
      dependence of the amide NH chemical shifts. These results demonstrate that
      conservation of the amide bond rigidity is essential for the activity of non
      hydrolyzable analogs.

PMID- 8748714
TI  - Synthetic Tyr-phospho and non-hydrolyzable phosphonopeptides as PTKs and TC-PTP
      inhibitors.
AB  - Tyrosine-specific protein kinases and phosphatases are important signal
      transducing enzymes in normal cellular growth and differentiation and have been
      implicated in the etiology of a number of human neoplastic processes. In order to
      develop agents which inhibits the function of these two classes of enzymes by
      interfering with the binding of their substrates, we synthesized analogs derived
      from the peptide EDNEYTA. This sequence reproduces the main autophosphorylation
      site of Src tyrosine kinases. In this work we report the synthesis, by classical
      solution methods, of the phosphotyrosyl peptide EDNEYpTA as well as of three
      analogs in which the phosphotyrosine is replaced by a phosphinotyrosine and by
      two unnatural, non-hydrolyzable amino acids 4-phosphonomethyl-L-phenylalanine and
      4-phosphono-L-phenylalanine. The Src peptide and its derivatives were tested as
      inhibitors of three non-receptor tyrosine kinases (Lyn, belonging to the Src
      family, CSK and PTK-IIB) and a non-receptor protein tyrosine phosphatase obtained
      from human T-cell (TC-PTP). The biomimetic analogues, which do not significantly
      affect the activity of CSK, PTK-IIB and TC-PTP, act as efficient inhibitors on
      Lyn, influencing both the exogenous phosphorylation and, especially, its
      autophosphorylation. In particular, the Pphe derivative may provide a basis for
      the design of a class of inhibitors specific for Lyn and possibly Src tyrosine
      kinases, capable of being used in vivo and in vitro conditions.

PMID- 8748715
TI  - Effect of trifluoroethanol on the solution structure and flexibility of
      desmopressin: a two-dimensional NMR study.

PMID- 8748716
TI  - Mast-cell-leukocyte cytokine cascades in allergic inflammation.

PMID- 8748717
TI  - The genetics of asthma and atopy.

PMID- 8748718
TI  - Aerobiologic and clinical aspects of mould allergy in Europe.

PMID- 8748719
TI  - Platelet-derived growth factor in asthma.
AB  - Platelet-derived growth factor (PDGF) controls cellular growth, migration, and
      differentiation. It is secreted by various cell types, including macrophages, and
      participates in tissue repair and epithelial regeneration. PDGF may therefore be
      involved in airway remodeling in asthma. This study compared the immunoreactivity
      of PDGF and its receptors (R alpha and R beta) in bronchial biopsies and the
      levels of PDGF in bronchoalveolar lavage (BAL) fluid of asthmatics and control
      subjects. Bronchial biopsies were done in a subsegmental bronchus of 11
      asthmatics and 11 control subjects by flexible bronchoscope. PDGF AA and BB, and
      PDGF receptors R alpha and R beta were studied with monoclonal antibodies and
      revealed by immunoperoxidase staining. The percentage of subjects presenting
      positive staining with PDGFs and its receptors was studied in the epithelium and
      submucosa. PDGF AA, AB, and BB were measured in BAL fluid of 18 asthmatics and 10
      controls by specific ELISA. In biopsies, there was no significant difference
      between asthmatics and controls for PDGF AA, BB, PDGF-R alpha and R beta
      (Fisher's exact test and Bonferroni's correction). Moreover, the levels of PDGF,
      AA, AB, and BB were similar in asthmatics and controls. This study does not
      support a role for PDGF in the repair processes of asthma.

PMID- 8748720
TI  - Antiallergic actions of high topical doses of terbutaline in human nasal airways.
AB  - It is debatable whether beta 2-receptor agonists produce antiallergic effects in
      human airways. This question has been addressed in the present study by
      examination of both mast-cell indices and the physiologic response to allergen
      challenge in human nasal airways. Twelve asymptomatic patients with seasonal
      allergic rhinitis were investigated outside the pollen season. Intranasal
      allergen provocation was carried out with diluent and three increasing doses of
      allergen. Topical terbutaline sulfate (1.0 mg) was given 5 min prior to each
      allergen challenge and nasal lavage was carried out 10 min after each challenge.
      The study design was double-blind, placebo-controlled, crossover, and randomized.
      The allergen challenge-induced mast-cell activation and the ensuing physiologic
      response of the airway tissue were investigated by measuring a mast-cell-derived
      mediator (tryptase) and plasma proteins (albumin and alpha 2-macroglobulin),
      respectively, in the lavage fluids. Allergen provocation produced dose-dependent
      increments of nasal symptoms and lavage fluid levels of tryptase, albumin and
      alpha 2-macroglobulin. Both nasal symptoms (P < 0.05) and lavage fluid levels of
      tryptase (P < 0.05), albumin (P < 0.05), and alpha 2-macroglobulin (P < 0.01)
      were reduced by pretreatment with topical terbutaline sulfate. We conclude that
      high doses of topical terbutaline may produce significant antiallergic effects in
      human airways by equally reducing both tryptase release and plasma exudation in
      the acute allergic reaction in human airways. Further studies are now warranted
      to determine whether microvascular antipermeability effects of beta 2-receptor
      stimulation contribute to the present observations.

PMID- 8748722
TI  - Basic isoforms of Par o 1, the major allergen of Parietaria officinalis pollen.
AB  - We describe a group of basic isoforms of Par o 1 (cumulatively referred to as Par
      o 1b), purified by anion-exchange chromatography. The allergenic activity of Par
      o 1b was compared with that of the acidic isoform (Par o 1a) by RAST inhibition.
      Par o 1b showed a cathodic mobility in crossed immunoelectrophoresis. It was
      found to be homogeneous in SDS-PAGE and SE-HPLC (14.5 kDa), and heterogeneous in
      PAG-IEF, yielding five IgE-binding bands with pI ranging between 7.9 and 9.6 PAG
      IEF individual components were isolated by cation-exchange HPLC. The N-terminal
      amino acid sequence of the main component (pI 8.8) was determined and found to be
      similar to that of Par o 1a.

PMID- 8748721
TI  - Allergen challenge in asthma: association of eosinophils and lymphocytes with
      interleukin-5.
AB  - To test whether eosinophil recruitment after pulmonary allergen challenge is
      associated with interleukin (IL)-5 in patients with asthma, we performed
      segmental bronchoprovocation (SBP) with saline, and with low and high dosages of
      ragweed extract in six patients with allergic asthma. Bronchoalveolar lavage
      (BAL) of the challenged segments was performed 5 min after challenge (immediate
      BAL fluid) and repeated 24 h later (late BAL fluid). Allergen challenge resulted
      in recruitment of eosinophils, and increased levels of eosinophil-active
      cytokines. A bioassay showed the predominant eosinophil-active cytokine in the
      late BAL fluids to be IL-5. Analysis of the late BAL fluids revealed that IL-5
      levels correlated with the numbers of eosinophils and lymphocytes. This study
      provides evidence that IL-5 is a critical cytokine associated with eosinophil and
      lymphocyte recruitment into the airways of patients with asthma following
      exposure to allergen.

PMID- 8748723
TI  - Exercise-induced bronchospasm (EIB) in relation to seasonal and perennial
      specific IgE in young adults.
AB  - We investigated the relationship between exercise-induced bronchospasm (EIB) and
      specific IgEs for seasonal (S-IgE) and perennial (P-IgE) allergens. The study,
      outside the main pollen season, was conducted on 289 20-year-old soldiers, who
      completed a self-administered questionnaire. A total of 289 subjects had S-IgE
      and P-IgE measured. The population was divided into subjects with (n = 166) and
      without (n = 123) history of atopic diseases (HAD). Twenty-three of 289 subjects
      (8%) had asthma, 70/289 (24%) allergic rhinitis, and 92/289 (32%) atopic
      siblings. Measured EIB was found in 17/289 subjects (6%). They had significantly
      higher levels of S-IgE and P-IgE than those without measured EIB (respectively, P
      < 0.01 and P < 0.05). The odds ratios of having EIB were significantly increased
      in the entire population in relationship with an increase in both S-IgE and P-IgE
      (chi-square test for trend = 9.4 and 12.7, P < 0.002 and 0.001, respectively).
      Interestingly, this highly significant relationship remained true when
      considering only the no HAD group (chi-square test = 7.4 and 8.8, P < 0.006 and
      0.003, respectively). Outside the pollen season, EIB was highly related to the
      level of both specific seasonal and perennial IgEs in the total population and in
      the subjects without HAD. This suggests that even in young adults who have been
      asymptomatic throughout their life EIB appears to be closely linked to seasonal
      or perennial allergic diathesis as measured by specific IgEs.

PMID- 8748724
TI  - An analysis of beta-lactam-derived antigens on spleen cell and serum proteins by
      ELISA and Western blotting.
AB  - Penicillins and related beta-lactam antibiotics are known to conjugate to
      proteins to generate potentially antigenic (haptenic) determinants. In the
      present study, we used a rabbit polyclonal antibody raised against
      benzylpenicillin (BP) to investigate the capacity of six penicillins and one
      cephalosporin to generate haptenic groups in vitro on cultured mouse spleen cells
      and on serum proteins in the culture medium. All of the drugs tested, namely, BP,
      amoxicillin (AMX), ampicillin (AMP), cephalothin (CEP), cloxacillin (CLX),
      flucloxacillin (FLX), and phenoxymethylpenicillin (PMP) generated antigens in a
      concentration-dependent manner on cell and serum proteins, which could be
      detected by ELISA, although antigens generated by BP, CEP, FLX, or PMP in either
      cell- or serum-conjugated form were more readily detected than those generated by
      AMX, AMP, or CLX. Western blot analysis revealed that BP-derived antigens were
      generated relatively slowly on cell proteins (maximum binding was not yet reached
      after 8 h), compared to serum proteins (maximum binding within 1 h). BP, CEP, and
      PMP all generated similar distinctive patterns of immunostaining of
      electrophoresed cell or serum proteins which did not reflect the relative
      abundance of different proteins as revealed by Coomassie brilliant blue staining.
      FLX, CLX, AMP, and AMX did not generate antigens that could be detected on
      Western blots. In conclusion, we have shown that various beta-lactam antibiotics
      generate antigens on cell and serum proteins that can be detected and
      characterized immunochemically with polyclonal antiserum. Further application of
      these methods may offer potential for further identification of immunologically
      relevant cellular and serum antigens generated by these drugs.

PMID- 8748725
TI  - Cross-reactivity of IgE-binding components between boiled Atlantic shrimp and
      German cockroach.
AB  - IgE-antibody reactivity to boiled Atlantic shrimp (Pandalus borealis) and German
      cockroach (Blattella germanica) of sera from 89 patients, sensitive to one or the
      other, was investigated with an enzymatic immunoassay for specific IgE detection
      (CAP-FEIA System, Pharmacia, Sweden). IgE serum levels to both antishrimp and
      anticockroach allergens were found to be positive in 76 of the 89 (85.4%) tested
      sera. A positive anticockroach IgE was very rare in the absence of detectable
      antishrimp IgE (five of 89 sera). Linear regression analysis on antishrimp and
      anti-German cockroach IgE levels-log plot revealed a correlation coefficient (r)
      of 0.73. Inhibition experiments showed that boiled Atlantic shrimp extract
      inhibited CAP with German cockroach, and vice versa. Immunoblotting showed the
      strongest IgE binding for both allergenic extracts between 30 and 43 kDa. By blot
      inhibition, the binding capacity of German cockroach was totally abolished by
      Atlantic shrimp extract, while German cockroach extract only partially IgE
      binding to Atlantic shrimp. Cross-reactivity exists between shrimp, an important
      food allergen, and German cockroach, which has an increasing role in allergic
      asthma. It could be important to determine the clinical significance of cross
      allergy to both allergens, in which exposures occur in different ways.

PMID- 8748726
TI  - Double-blind trial of house-dust mite immunotherapy in asthmatic children
      resident at high altitude.
AB  - Twenty-three Dermatophagoides pteronyssinus (Dpt)-sensitive asthmatic children
      aged 7-14 years entered a double-blind, placebo-controlled trial of standardized
      immunotherapy (IT) (Alpare) while resident at high altitude. Dpt sensitivity was
      evaluated by skin prick tests at different allergen concentrations at the
      enrollment and after 6 and 12 months of treatment. Bronchial hyperreactivity was
      evaluated at the same time points, and on each occasion, histamine challenge and,
      the following day, Dpt bronchial challenge were performed. All patients,
      irrespective of active treatment, improved clinically and in lung function with
      increased PC20 and Dpt-PD20. Alpare-treated patients had a significantly
      decreased sensitivity on Dpt skin testing (P < 0.009) and felt that their asthma
      had improved (P < 0.001) compared with placebo-treated subjects, but there was no
      difference between the treatment groups in lung function or bronchial challenge
      response. IT neither increased nor decreased bronchial histamine sensitivity. Our
      results indicate that Dpt IT benefits asthmatic children, but improvement by
      allergen avoidance at high altitude is even greater.

PMID- 8748727
TI  - Reactions to airborne fish particles.

PMID- 8748728
TI  - Steady-state models in electrophoresis: from isotachoporesis to capillary zone
      electrophoresis.
AB  - Although all electrophoretic techniques are closely allied and controlled by the
      same rules, we often distinguish between steady-state and dynamic models in the
      modeling of electrophoretic processes, whereby steady-state models are applied
      for isotachophoresis (ITP) and dynamic models are applied for other
      electrophoretic processes, wherein a steady-state is not reached. This paper
      shows how, starting from a mathematical model for the steady-state in ITP,
      mathematical models can be derived for several modifications of ITP and that even
      nonsteady-state processes can be estimated by a repeated application of a steady
      state model. In this way all parameters in sample zones in capillary zone
      electrophoresis (CZE), through which temporal electropherograms can be simulated,
      can be calculated. Realistic simulations can be obtained for zone electrophoretic
      processes, for which the electrodispersive character is the dominating peak
      broadening mechanism, and simulated electropherograms resemble measured
      electropherograms concerning migration times, peak shapes, fronting or tailing
      character and the question of peaks and dips.

PMID- 8748729
TI  - Theory of zone separation in isotachophoresis: a diffusional approach.
AB  - The qualitative characteristics of isotachophoresis differ substantially from
      "classical" separation methods such as chromatography or zone electrophoresis.
      Self-sharpening zone boundaries and step-like concentration profiles are the most
      specific features of this method, which does not allow the description of the
      isotachophoretic separation in usual "chromatographic" terms, such as resolution
      or number of theoretical plates. A theory is presented in this paper, combining
      the usual isotachophoretic separation characteristics with the theory of
      isotachoporetic zone boundary, which is the only element of the isotachophoretic
      system with dispersional properties. This allows us to consider situations near
      the limits of the isotachophoretic method as far as both selectivity and sample
      amount (i.e., zone size) are concerned. Based on a simplified expression of the
      concentration profiles across the isotachophoretic zone boundary, separation and
      separation limits are described and discussed in terms of resolution, selectivity
      and zone capacity. Equations are derived showing the relationships between
      resolution, boundary width, selectivity, sample amount, and column and
      electrolyte conditions. A simple phenomenological equation is presented,
      expressing isotachophoretic resolution as a function of only sample amount (or
      sample zone length) and boundary width. A thermodynamic form of this equation is
      derived, which is shown to be similar to such an expression for resolution in
      zone electrophoresis. In both cases resolution is a function of sample
      selectivity, electric field strength and column length. A simple theoretical
      model for zone capacity is presented, making it possible to estimate the
      separation performance of isotachophoretic systems. Based on the presented
      theory, parallels between isotachophoresis and zone electrophoresis are discussed
      and both methods are compared.

PMID- 8748730
TI  - Training software for electrophoresis.
AB  - Computer programs, simulating electrophoretic separations, were evaluated and
      discussed with respect to their suitability for training purposes. Quite a number
      of them, mainly those dealing with steady-state phenomena, are sufficiently fast
      and user-friendly for the purpose of visualization of electrophoretic principles.
      Transient-state or dynamic models, however, are more suitable for the advanced
      user, mainly because of their inherent complexity and long calculation times.

PMID- 8748731
TI  - Impact of electroosmosis on isotachophoresis in open-tubular fused-silica
      capillaries: analysis of the evolution of a stationary steady-state zone
      structure by computer simulation and experimental validation.
AB  - A dynamic computer model for simulation of open-tubular capillary electrophoresis
      that includes in situ calculation of electroosmosis along the fused-silica
      capillary column has been applied to the characterization of an anionic
      isotachophoretic system in presence of a cathodic electroosmotic flow. For each
      column segment, electroosmosis is calculated with the use of a wall mobility, the
      voltage gradient and the degree of dissociation of the silanol surface groups of
      the capillary wall. Then, the bulk capillary flow is taken to be the average of
      all of the segment flows and considered to represent a plug flow. This simple
      approach enables the combined simulation of the temporal behavior of an
      isotachophoretic zone structure in presence of electroosmosis. For a model
      anionic isotachophoretic configuration at pH 6, simulation data reveal the
      asymptotic formation of a stationary steady-state zone configuration in which
      electrophoretic and electroosmotic zone displacements are opposite and of equal
      magnitude. The position of the stationary boundaries are predicted to be
      dependent on the selected wall pK and mobility values. For two different
      instruments, qualitative agreement between experimental data and simulation
      results obtained with a wall pK between 5 and 6 is demonstrated. However, for the
      two experimental setups, significant differences in electroosmotic pumping (i.e.
      wall mobility values) are noted.

PMID- 8748732
TI  - Dynamics of peak dispersion in capillary zone electrophoresis including wall
      adsorption: II. Exact analysis of unsteady linear adsorptive dispersion.
AB  - An exact analysis of the unsteady axial dispersion of an analyte, undergoing a
      linear adsorption at the column wall in capillary zone electrophoresis, is
      presented. A system of partial differential equations--in which the radial
      coordinate is one of the independent variables--is taken as a model for linear
      wall adsorption. It is shown that the dispersion is a sum of two terms, one which
      depends linearly on time and whose exact form is generally known, and a non
      linear one. The most interesting result of this work is that it derives another
      system of differential equations, which this nonlinear term is to satisfy. It
      makes it possible to present a closed formula for the asymptotic value of the
      nonlinear term, i.e., its limit for large time. Its behavior for times close to
      zero is also studied.

PMID- 8748733
TI  - Contribution of capillary coiling to zone dispersion in capillary zone
      electrophoresis.
AB  - A mathematical model of the deformation of the analyte zone in capillary zone
      electrophoresis (CZE) due to capillary coiling is presented and the influence of
      capillary coiling on the distribution of electric current density inside the
      capillary is described. The model gives a quantitative description of the
      potential contribution of capillary coiling to the total zone dispersion in CZE.
      The zone broadening caused by capillary coiling is calculated as the difference
      of migration distances of the particles migrating at the inner circumference of
      the capillary coil and those migrating at the outer circumference. This
      difference is shown to be directly proportional to the capillary diameter and to
      the number of capillary coils, i.e. indirectly proportional to the radius of the
      capillary coils into which the capillary of the given length is coiled. The
      contribution of capillary coiling to the total zone dispersion is compared with
      the contribution of the longitudinal diffusion of low and high molecular mass
      analytes and bioparticles. It is shown that, especially in the case of CZE
      separation of macromolecules and particles, capillary coiling can significantly
      decrease the separation efficiency. For that reason the small radius coiling of
      the capillary column in the CZE apparatuses should be avoided.

PMID- 8748734
TI  - Sample self-stacking and sample stacking in zone electrophoresis with major
      sample components of like charge: general model and scheme of possible modes.
AB  - A theoretical study is presented of zone electrophoretic behavior of samples that
      contain one or more minor analytes and at least one major ionogenic component of
      like charge. Based on a simple model comprising weak univalent anionic
      electrolytes, conditions are derived under which analytes are temporarily focused
      isotachophoretically into very narrow zones by a sample self-stacking effect
      provided by the major sample components. Requirements for minimal/maximal
      mobility and a background coion concentration dependent minimal concentration of
      a major sample component (stacker) are presented. For systems in which sample
      self-stacking does not apply, an expression for the concentrating factor is
      derived that involves the effects of both nonselective (classical) and selective
      sample stacking, the latter being a consequence of electrophoretic separation of
      the minor analyte from the major component. The theory derived is discussed with
      selected model examples by using both numerical calculation and computer
      simulation.

PMID- 8748735
TI  - Capillary electrophoresis of peptides using rectangular and cylindrical
      geometries: a comparative study.
AB  - A study on the use of rectangular columns in capillary zone electrophoresis (CZE)
      is presented. The equations controlling the hydrodynamic flow and the plate
      height in rectangular capillaries are deduced. Several experiments were carried
      out in order to test the validity of these equations. Also, the possibilities of
      these columns in terms of thermal dissipation, efficiency, analysis speed and
      sample capacity were studied and compared with those for cylindrical tubing. The
      results from both rectangular and cylindrical columns are compared to each other,
      employing the parameters mentioned above, and also with those predicted by
      theory. The advantages, i.e. better heat dissipation, higher speed and larger
      sample capacity, and drawbacks, i.e. high fragility and incompatibility with some
      capillary electrophoresis instruments, of employing rectangular geometries in CZE
      are discussed.

PMID- 8748736
TI  - Model of isotachophoresis (displacement electrophoresis) in tapered capillaries.
AB  - The principle and theoretical description of boundary focusing under
      electrophoretic migration in a tapered capillary are presented. The model
      describes the gradual volume decrease of a moving boundary between weak
      electrolytes or ampholytes. The relations between the departure from the local
      steady state, the ratio of inlet to outlet capillary cross section, the effective
      mobilities and the selectivity are formulated. They allow the selection of
      operating conditions such that the departure from the local steady state can be
      decreased to an acceptable level. The relations predict that isotachophoresis
      (displacement electrophoresis) in a capillary with a shallow taper can maintain a
      constant ratio of actual boundary width to local steady state width, provided
      that the local capillary cross section decreases linearly with length. The
      significance of some assumptions needed for the model formulation is analyzed.
      Numerical examples are given indicating the method feasibility.

PMID- 8748737
TI  - Dynamic control to improve the separation performance in capillary
      electrophoresis.
AB  - Dynamic control in capillary electrophoresis (CE) is able to provide better
      resolution, shorter separation time, reduced band broadening and better
      reproducibility for the separations of organic and inorganic ions and large
      molecules such as proteins and DNA. This article provides an overview of dynamic
      control in CE by several techniques: pH, temperature, external electric field,
      and field amplification. These techniques take advantage of the changes in
      electroosmotic flow coefficient, electrophoretic mobilities of the analytes due
      to changes in equilibrium, viscosity of the buffer solution, and/or electric
      field strength. The basic theories and applications to the improvement of the
      separation performance for standard samples in CE by using these dynamic control
      techniques are presented. Finally, the advantages and shortcomings of these
      techniques and the future trends of dynamic control for the separations of real
      samples are discussed.

PMID- 8748738
TI  - Viscous effects in capillary electrophoresis: theory and experiment.
AB  - Simple theory which relates the viscous effects of additives used in capillary
      electrophoresis (CE) to resolution and resolution per unit time are developed for
      small molecule separations in the absence of sieving effects. The resolution
      theory shows that there is no advantage to using viscous additives for resolution
      improvement unless either a binding energy difference exists between the solutes
      and additive, or viscous effects cause a reduction in the vector sum of
      electrophoretic and electroosmotic velocities when these are of opposite sign. In
      general, increasing the viscosity is shown to result in a loss of resolution per
      unit time. Theory demonstrates that in cases where only binding is considered to
      be present, the maximum resolution increase is found to be at relatively small
      amounts of additive. In addition, specific regions of the elecctrophoreogram may
      demonstrate resolution enhancement at a specific concentration while other
      regions exhibit a resolution decrease, as compared to no additive present. CE
      separations of the components in a Triton surfactant, conducted using a
      polyethylene glycol (PEG) additive, demonstrate that improved resolution for some
      of the peaks exists at a specific PEG concentration. These results are mostly
      explained through the reduction in electroosmotic flow velocity that takes place
      through additive adsorption to the capillary wall, although some binding is
      present.

PMID- 8748739
TI  - Electrophoresis between sieving and reptation: an investigation of the role of
      shape fluctuations in electrophoresis.
AB  - We present numerical simulation results of electrophoretic mobilities of flexible
      polyelectrolytes over a wide molecular size range moving through gels with
      various pore sizes. The data are compared to existing models for different
      molecular size regimes and to experimental results. We observe rather pronounced
      shape fluctuations of the polyelectrolytes which, especially for larger gel pores
      or small molecules, have a strong impact on the dynamics of the molecules.
      Electrophoretic separation, as is used e.g. for DNA sequencing, is best achieved
      for polyelectrolytes with a radius of gyration of the order of the average pore
      radius of the gel, i.e. in a molecular size regime where the polyelectrolyte
      interacts with only a few gel fibers at a given time. A decrease of the gel pore
      size leads to a systematic decrease of the electrophoretic mobility, but does not
      lead to a qualitative change in the molecular size dependence, as long as the
      pore size is larger than the persistence length of the polyelectrolyte.

PMID- 8748740
TI  - Capillary electrophoresis with polymeric separation media: considerations for
      theory.
AB  - The theory of capillary electrophoresis with polymeric separation media is
      reviewed. Some of the major theories of gel electrophoresis are examined in terms
      of the experimental observations that they support. The considerations and
      difficulties in applying these theories to capillary electrophoresis with
      polymeric separation media are investigated, particularly the use of high
      electric field strengths and low concentration polymer solutions. Recent advances
      in this area, including some empirically-derived relationships and models
      currently found in the literature, and future directions for theory development
      are discussed.

PMID- 8748741
TI  - A quantitative study on the effect of organic modifiers in micellar
      electrokinetic chromatography.
AB  - A quantitative study was made on the effect of organic modifiers in micellar
      electrokinetic chromatography (MEKC). A linear relationship between 1/k' and
      organic modifier concentration ([L]) at lower concentration range was derived and
      experimentally verified. This linearity was also examined at higher
      concentrations of organic modifier. The results showed that the linear
      relationship between 1/k' and [L] can only be observed under the situation that
      no significant change on micellar structure occurs upon the addition of organic
      modifiers. The mobility ratio of the solute which characterizes the properties of
      the solute was found to be mainly independent of [L]. A resolution equation for
      the neutral solutes was also derived in term of mobility ratio.

PMID- 8748743
TI  - Capillary isoelectric focusing: a routine method for protein analysis?
AB  - Although isoelectric focusing (IEF) in the slab gel format is a widely used
      technique in protein analysis, capillary isoelectric focusing (CIEF) is not yet a
      method used routinely, despite major advantages. This may be due to the fact that
      several methods for performing IEF in the capillary can be found in the
      literature, differing in the manner of mobilizing the focused protein zones for
      detection. We therefore discuss and compare the three most widely used CIEF
      techniques - using chemical, pressure, or electroosmotic flow (EOF) mobilization 
      with respect to linearity of the calibration curve, resolution, and
      reproducibility.

PMID- 8748742
TI  - Study of high-field dispersion in micellar electrokinetic chromatography.
AB  - The anomalous dispersion of hydrophobic, highly retained analytes at high
      electric field strengths E in micellar electrokinetic chromatography (MEKC) is
      experimentally and theoretically quantified. A simple model for plate number N is
      proposed, in which only plug size and longitudinal diffusion govern dispersion.
      This model describes well the dispersion of acetone, 2'-deoxyadenosine, and 2'
      deoxyadenosine-5'-monophosphate (dAMP) in MEKC buffers and also dAMP in capillary
      electrophoresis buffers. However, the model describes the dispersion of 1
      nitropyrene, pyrene, perylene, and the 4-chloro-7-nitrobenzofuran (NBD)
      derivative of cyclohexylamine only at low E's; for these analytes, a
      nonequilibrium-like dispersion causes N to decrease rapidly at high E's.
      Furthermore, the dispersion of NBD-cyclohexylamine has a dependence on capillary
      diameter. Theoretical arguments are proposed, which show that this additional
      dispersion cannot be explained quantitatively by mass-transfer kinetics, micellar
      polydispersity, hydrodynamic flow, Joule heating, or the radial variation of
      partition coefficient. In addition, experiments are performed suggesting that
      wall adsorption and sample inhomogeneity are not responsible for the efficiency
      loss. Other dispersion sources are suggested for future exploration.

PMID- 8748744
TI  - Chiral separation in capillary electrophoresis.
AB  - A mathematical model which explains separation in chiral capillary
      electrophoresis is presented. The model is analysed to give a more general
      solution than previous work and is supported by further experimental work.

PMID- 8748745
TI  - Electroosmotic control of chiral separation in capillary zone electrophoresis.
AB  - The resolution in capillary zone electrophoresis (CZE), with the assumption of
      diffusion control only, is strongly dependent on the direction and magnitude of
      electroosmotic flow. In fact, excellent separation resolution will be obtained if
      the electroosmotic flow is in the opposite direction of the electrophoretic
      migration. By applying various radial electric potential gradients across the
      capillary wall, the direct control of the zeta potential and the electroosmotic
      flow results in a great enhancement of chiral resolution in cyclodextrin-modified
      CZE. All 12 basic chiral drugs, including (+/-)-ephedrine, (+/-)-pseudoephedrine,
      (+/-)-norephedrine, (+/-)-epinephrine, (+/-)-norepinephrine, and (+/-)
      isoproterenol, are separated and resolved within 22 min of the analysis time.
      There is no additional band broadening and dispersion introduced by the direct
      control of electroosmosis with the application of various radial electric
      potential gradients.

PMID- 8748746
TI  - Theory of capillary electrophoretic separations of DNA-polymer complexes.
AB  - Electrophoretic separation of DNA molecules normally requires the use of an
      anticonvection, sieving polymer matrix such as a gel or an entangled polymer
      solution. Recently, it has been suggested that free-solution separation could be
      achieved in a capillary if an electrically neutral, friction-generating molecule
      is attached to the DNA molecules before electrophoresis is carried out. The
      electrophoretic mobilities are then predicted to be very large and the resulting
      separation is expected to yield excellent resolution. The size-dependence of the
      electrophoretic mobility is attributed to longer DNA molecules pulling the
      neutral molecule with a larger electric force, thus eluting earlier than shorter
      DNA molecules. In this article, we focus on the particular case where one
      attaches an uncharged, flexible polymer to the end of the DNA. Our self
      consistent model takes into account the deformation and the hydrodynamic
      resistance of the polymer in the flow. We find various regimes, depending on the
      intensity of the electric field and the length of the polymer. The most favorable
      conditions for high-resolution separation of DNA are described.

PMID- 8748747
TI  - Application of chemometric experimental designs in capillary electrophoresis: a
      review.
AB  - Various chemometric experimental designs have been employed for the optimisation
      of capillary electrophoresis (CE) methods. Similar designs have been utilised in
      the assessment of the robustness of CE methods. The designs employed include
      central composites, fractional factorials, Plackett-Burman, simplex and
      overlapping-resolution mapping. Optimisation studies have largely concentrated on
      the use of these designs on selection of the optimal electrolyte composition. The
      robustness testing studies performed have involved the use of screening designs
      to identify the critical parameters affecting responses such as migration times
      and resolution. Further designs such as central composites have then been
      employed to set method limits following robustness studies. It is concluded that
      the use of experimental designs and statistical data evaluation in conjunction
      with personal computer-controlled CE autosamplers and instruments are of great
      benefit in the optimisation and robustness evaluation of CE methods.

PMID- 8748748
TI  - On the measurements of electrophoretic mobilities by means of capillary
      isotachophoresis at a constant voltage.
AB  - A method for measuring electrophoretic mobilities by means of isotachophoresis
      (ITP) at a constant voltage as described by H. Carchon and E. Eggermont
      (Electrophoresis, 1982, 3, 263-274) is analyzed. An error made in this work,
      disregarding the pH shift arising at the initial discontinuity on the leader
      terminator boundary, has been corrected. This method has been carefully studied
      and generalized for the presence of constant electroosmotic flow in a capillary.
      The limits of its applicability and the diffusionless ITP theory in general are
      discussed. A detailed study of the evolution of initial discontinuity (stationary
      boundary) showed some anomalies not reported previously, particularly non
      monotonic concentration profiles in the vicinity of stationary boundaries.
      Moreover, in some cases, diffusion effects and the contribution of H+ ions can
      also strongly influence the behavior of moving boundaries. Computer modelling
      (confirmed by experimental data) showed that these effects could lead to the
      decay of the ITP train, despite the fact that the steady state diffusionless ITP
      theory predicts its stability.

PMID- 8748749
TI  - Some variables affecting reproducibility in capillary electrophoresis.
AB  - Several variables that can affect reproducibility of both the peak height and the
      migration time in capillary electrophoresis (CE) were investigated here. A great
      part of the imprecision in CE for migration time is related to the interaction of
      the analyte with the capillary wall. Within a run, acidic compounds with long
      migration times have a higher relative standard deviation. In general, conditions
      that decreased the migration time, such as a short capillary length, tended to
      enhance the reproducibility of the migration time. Sample size also affected the
      reproducibility of peak height. Too small or too large an injection volume
      diminished the reproducibility. Sample matrix, such as high levels of proteins or
      salts in the sample, decreased the reproducibility. Furthermore, improvement in
      reproducibility can be achieved by using internal standards (especially for
      migration time), thorough washing of the capillary, or removing the excess
      proteins by acetonitrile deproteinization. Acetonitrile has an added effect of
      producing sample stacking. Depending on the migration time and analyte
      concentration, the peak height and area yielded different reproduciblity results.

PMID- 8748750
TI  - Capillary enzymophoresis of nucleic acid fragments using coupled capillary
      electrophoresis and capillary enzyme microreactors having surface-immobilized RNA
      modifying enzymes.
AB  - This report describes the coupling of capillary enzyme reactors to capillary
      electrophoresis, which is termed capillary enzymophoresis. In the present study,
      the capillary enzyme reactors were prepared by immobilizing RNA-modifying
      enzymes, e.g., RNAse T1 and RNAse U2, on the inner walls of 50 microns fused
      silica capillaries. These microreactors served to selectively modify the solutes
      (or substrates) before entering the separation capillary. Capillary
      enzymophoresis using single or mixed enzyme reactors proved useful in identifying
      minute amounts of dinucleotides as well as the fingerprinting of tRNAs. The
      immobilized RNase T1 and RNase U2 displayed their usual enzymic activities toward
      RNA fragments and in addition exhibited different activity-pH dependency than the
      soluble enzymes. This was attributed to microenvironmental effects arising from
      the charged nature of the capillary walls in the close proximity of the
      immobilized enzymes. The enzyme reactors were reusable for several RNA samples
      and showed chemical and thermal stability.

PMID- 8748751
TI  - Fragment excision versus conventional disc removal in the microsurgical treatment
      of herniated lumbar disc.
AB  - 100 patients who had a lumbar microdiscectomy were retrospectively compared with
      100 microsurgically treated patients who had only a removal of the herniated disc
      fragment. We were able to show that there are less "reherniations" in the
      fragment removal group and the clinical outcome is often better regarding
      postoperative problems of instability.

PMID- 8748752
TI  - Hypoglosso-facial nerve anastomosis.
AB  - The hypoglosso-facial nerve anastomosis (HFA) is a valuable surgical procedure
      for the treatment of certain types of facial paralysis. HFA was performed 1 to 22
      months after resection of an acoustic neurinoma in 32 patients where the
      operation was complicated by unilateral facial palsy. 56% of these patients
      obtained excellent facial function, and a total of 66% were satisfied and would
      have repeated the operation even with their present knowledge about the
      disadvantages. The recovery of facial function after any nerve anastomosis or
      plastic procedure is never perfect but HFA usually results in symmetry of the
      face in response and animation of the face during conversation. HFA is most
      effective when used as soon as possible after facial palsy has developed,
      provided a sufficient time has passed for any possible spontaneous recovery. This
      waiting period should not exceed six months. If the operation is done promptly
      the results improve, probably because only slight atrophy has occurred in the
      facial muscles. The disadvantages of HFA are hemiatrophy of the tongue, mass
      movement of the face and, in some instances, hypertonia of the face. The
      advantages are improved facial tone with ameliorated cosmetic result, protection
      of the eye, intentional facial movements controlled by the tongue, and movements
      associated with physiological function of the tongue.

PMID- 8748753
TI  - Moderate head injuries in children as compared to other age groups, including the
      cases who had talked and deteriorated.
AB  - Patients defined as having a moderate head injury on the basis of Glasgow Coma
      Scale scores within the ranges of 9 to 13 after acute nonsurgical procedures were
      selected. Almost 1600 cases were hospitalized in the Neurosurgery Department. The
      cases were admitted through the Emergency Unit of Gaz University Medical School,
      Ankara, Turkey during the period between 1979 and 1992. The group studied
      consisted of 231 selected patients assessed separately in paediatric, adult and
      elderly age groups. Possible risk factors such as: GCS score, anisocoria,
      unilateral or bilateral fixed pupils, impaired oculocephalic reflexes, presence
      of multiple systemic injuries, aetiology of head trauma, presence of linear or
      depressed skull fractures, space occupying mass on CT or operation was also
      assessed. Subarachnoid haemorrhage turned out to be the only independent
      significant risk factor in predicting mortality. The data about the patients who
      have "talked and deteriorated" were also reported so as to assisst physicians
      charged with the care of trauma victims.

PMID- 8748755
TI  - A long-term follow-up study in direct cerebral aneurysm surgery.
AB  - A long-term follow-up study covering between one and twenty-two years after
      surgery was carried out on 177 patients with direct operations for cerebral
      aneurysms. Rebleeding was detected in five out of 18 patients with incomplete
      operations; one patient within 6 months and four patients within 5 to 8 years
      after surgery. The rebleeding rate of incompletely operated patients in the first
      decade was similar to that of untreated patients with ruptured aneurysms. This
      suggests that wrapping, coating and incomplete clipping procedures provide some
      protection against rebleeding in the first 6 months but little in the period
      extending beyond 5 years after surgery. Showing two types of newly-formed
      aneurysms after complete surgery and enlarged residual aneurysms after incomplete
      surgery, the possibility of rebleeding from these aneurysms is discussed in the
      present report.

PMID- 8748754
TI  - Cerebral oedema after subarachnoid haemorrhage. Pathogenetic significance of
      vasopressin.
AB  - The authors report the frequency, characteristic clinical symptoms, laboratory
      alterations and diagnostic criteria of the syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH) after subarachnoid haemorrhage. The data on 290
      patients with subarachnoid haemorrhage (SAH) during a period of years at the
      Division of Neurosurgery, University Medical School, Szeged, are analysed. Twenty
      seven (9.3%) patients developed SIADH. Thirteen (4.5%) patients had severe and 14
      (4.8%) had mild SIADH. The problems of the treatment are discussed in detail and
      the different therapeutic methods are listed: NaCl infusion, water withdrawal and
      administration of Dilantin, diuretics, mineralocorticosteroids, lithium and
      demeclocycline. The undesirable side-effects observed accompanying various
      therapeutic regimen are analysed. The introduction of V2 antagonists into
      clinical practice appears to be a most perspective procedure. For study of the
      pathogenesis of SIADH following SAH, the possibility of treatment with V2
      antagonists on an experimental model of SAH in rat was created. A significant
      water retention and increases in brain water and sodium content were observed in
      rats with SAH. Plasma AVP levels were also elevated after SAH. AVP plays an
      important role in the development of antidiuresis following water loading and
      disturbance of the brain water and electrolyte balance after SAH. Water retention
      and the higher brain water and sodium accumulation could be totally prevented by
      administration of a V2 antagonist. These results demonstrate that cerebral oedema
      generated by artificial cerebral bleeding in rats is significantly reduced
      following the administration of a highly specific V2 antagonist, suggesting a new
      approach to the treatment of SIADH.

PMID- 8748756
TI  - Significance of ST segment elevation in electrocardiograms in patients with
      ruptured cerebral aneurysms.
AB  - Twenty-three patients with aneurysmal subarachnoid haemorrhage (SAH), who showed
      an ST segment elevation in their electrocardiograms (ECG), were examined. There
      were 12 males and 11 females, with a mean age of 61 years. The clinical condition
      on admission was Hunt and Kosnik grade II in four, III in seven, IV in one, and V
      in 11 patients. Computerized tomography (CT) also revealed many cases of diffuse,
      thick SAH or intracerebral or intraventricular haematoma. Laboratory examinations
      including serum electrolyte, pH, and PaO2 revealed no abnormalities that might
      have influenced the ECG. Elevation in the levels of myocardial enzymes in serum
      was observed in two of the nine patients examined, although the elevation was
      only slight in one of them. Echocardiography, which was performed on several
      occasions on all patients, and cardiac catheterization, which was performed on
      eight patients, revealed a reduction in the motion of the left ventricular apex
      that was synchronous with ST segment elevation. This is the first report about
      these phenomena. No abnormalities were observed in the coronary artery. The
      elevated ST segment was normalized within one week in all patients, accompanied
      by normalization of the apical wall motion recorded on echocardiograms. In four
      patients, however, T wave inversion accompanied the improvement of the ST segment
      and was normalized within three months after the onset. These results suggest
      that ST segment elevation in the acute stage of SAH reflects transient cardiac
      dysfunction rather than myocardial injury. In some patients, however, the
      elevated serum levels of myocardial enzymes or T wave inversion suggested the
      presence of myocardial injury. Close follow-up seems to be necessary in such
      cases.

PMID- 8748757
TI  - In vitro and in vivo efficacy of a rifampin-loaded silicone catheter for the
      prevention of CSF shunt infections.
AB  - Infection of cerebrospinal fluid (CSF) shunts is one of the major complications
      associated with their use and is usually managed by shunt removal, temporary
      insertion of an external drainage and implantation of a new shunt system. We have
      evaluated the efficacy of a rifampin-loaded silicone ventricular catheter to
      prevent bacterial colonization and infection in vitro and in an animal model. On
      the basis of an incorporation process a rifampin-loaded catheter was developed
      which is capable of releasing rifampin in bacteriocidal concentrations for 60
      days and more. In a stationary bacterial adherence assay using S. epidermidis as
      test strain, the colonization resistance of the device was demonstrated. To
      assess the capability of the catheter to prevent CSF shunt infections, a rabbit
      model was developed which allowed the establishment of a reliable and
      reproducible CSF infection by implantation of silicone catheters into the
      ventricle and inoculating S. epidermidis (minimal dose 10(6) cfu) or S. aureus
      (minimal dose 10(3) cfu). Rifampin-loaded catheters (12 animals inoculated with
      S. epidermidis, 8 animals inoculated with S. aureus) were compared with non
      loaded (14 animals inoculated with S. epidermidis, 19 animals inoculated with S.
      aureus) control catheters, and infection was documented by clinical,
      microbiological and histological methods. In contrast to the control group, none
      of the animals with rifampin-loaded catheters showed clinical signs of infection.
      Furthermore, in none of the materials obtained after sacrifice of the animals
      (catheter, brain tissue, CSF, blood) could the infecting bacteria be cultured,
      whereas in materials from animals with the unloaded catheter the infecting
      strains could always be cultured from the catheter and from surrounding brain
      tissue. The histological examination of catheter-adjacent tissue supported these
      findings. We conclude that a rifampin-loaded silicone ventricular catheter is
      capable of completely preventing bacterial colonization and infection by
      staphylococci as the main causative organisms in CSF shunt infections and should
      be further evaluated in clinical trials.

PMID- 8748758
TI  - Computer-assisted multidimensional atlas for functional stereotaxy.
AB  - Functional stereotactic operations are currently performed primarily for
      medically uncontrollable Parkinson's disease and pain. In contrast to the targets
      in neuro-oncology, those in functional stereotaxy cannot be represented directly
      by modern imaging methods. The target co-ordinates must therefore be calculated
      with the aid of special stereotactic atlases. These are publications in which a
      model brain has been constructed from autopsy examinations on a number of brains,
      or the data obtained have been compiled in the form of tables and histograms on
      which the calculation is then based. The target can then be determined based on
      the classic stereotactic landmarks and reference lines, such as the anterior
      commissure (AC), the foramen of Monro (FM), the posterior commissure (PC) or the
      base line FM-PC or AC-PC and the height of thalamus, taking into account the
      interindividually different anatomical proportions. Since the computational
      procedures involve repetitious algorithms, it was obvious that such procedures
      should be run by a computer program. For the most common stereotactic targets, we
      have developed a computer program for data storage on the one hand and
      computation and graphic output on the other. The output can be displayed on the
      monitor and can also be plotted out on paper or overhead transparency.
      Calibrating between the program and printer renders a 1:1 reproduction, i.e. the
      graph can be superimposed directly onto original x-rays or images from computed
      tomography or nuclear magnetic imaging. The graph can be plotted in the three
      dimensions of the Cartesian co-ordinate system. An additional dimension can be
      attained by simultaneously including and plotting the data from different atlases
      and thus from different authors, including one's own data. In addition to the
      information capacity which this system offers, it also makes possible a
      considerable reduction in the time for computing the target while at the same
      time increasing the reliability.

PMID- 8748759
TI  - Tumour response and morphological changes of acoustic neurinomas after
      radiosurgery.
AB  - Twenty-seven of the 1560 patients treated by radiosurgery during the period 1984
      1993 had acoustic neurinomas. Four cases were excluded from this study because
      they had a follow-up of less than 2 years. There were 24 neurinomas treated in 23
      patients as one patient had a bilateral tumour. Seven patients underwent
      radiosurgery for a recurrent tumour (already operated on once or twice), while it
      was the first treatment for 16 patients. The tumour volume ranged from 1.99 cm3
      to 18.30 cm3, and the patient follow-up was from 2 to 8 years. To determine the
      target on CT/NMR for linear accelerator stereotactic irradiation, the Greitz
      Bergstrom non-invasive head fixation device was used. It was again adopted for
      subsequent serial imaging, and for repeat radiosurgery when necessary. The total
      peripheral tumour dose ranged from 12 to 45 Gy. In 9 patients there was a
      reduction in tumour volume varying from 39 to 100%, while 14 of the neurinomas
      appeared stable after an average follow-up of 3 years. In one patient there was
      an increase in size of the tumour. Variable morphological changes were present in
      66% of the neurinomas treated. Radiosurgery is indicated as an alternative to
      microsurgery for inoperable patients and for those who refuse surgery, for
      recurrent tumours, and as a post-operative complementary treatment for partially
      removed tumours. A gradual approach to radiosurgery, depending on tumour
      response, allows a greater efficacy with minimal risk. In the present series no
      complications were observed. Hearing was preserved at almost the same level as
      that prior to radiosurgery in all patients.

PMID- 8748760
TI  - Circulating immune complexes in intracranial neoplasms.
AB  - The levels of circulating immune complexes (CIC) were assayed in the sera of 109
      patients with intracranial space occupying lesions. The CIC levels were
      significantly increased in all the brain tumours. After treatment, the CIC levels
      were still significantly increased when compared to the controls but showed no
      change when compared to their respective pre-operative values. Further, no change
      was observed in the CIC levels between the malignant and benign tumour case.
      Moreover, in brain tumours, 90% of the CIC precipitate consisted of IgG. However,
      the CIC levels fail to prognosticate the process of the disease in these
      patients.

PMID- 8748761
TI  - Cavernous angioma associated with oligo-astrocytoma-like proliferation. Report of
      two cases and review of the literature with a reappraisal of the term
      "angioglioma".
AB  - Reporting two cases of cavernous angioma closely associated with oligo
      astrocytoma we were stimulated to revise the proper use of the term
      "angioglioma", introduced by Councilman 80 years ago7. In the past this term was
      often used in a merely descriptive sense i.e. either to give a name to an
      exceptional coincidence of AVM and glioma or simply to describe a
      hypervascularized glioma. Today, according to the majority of authors, such a use
      of this term has to be rejected as inappropriate. Occasionally however the term
      angioglioma has been used to designate a true mixed composite neoplasm developed
      after the transformation of both glial and angiogenic elements determined by
      simultaneously or consecutively acting (even possibly intermingled) oncogenic
      factors. Among reported cases claimed to be examples of "true" angioglioma, the
      association cavernomaoligodendroglioma/astrocytoma seems the most intriguing
      besides being also the most frequent one. Opinions about this topic however did
      continue to be unequivocal. While some authors regarded the oligodendroglial
      proliferation associated with AVM as merely reactive or malformative, others
      considered it as truly neoplastic putting forward the hypothesis of a common
      viral or genetic aetiology for both AVM and glioma.

PMID- 8748762
TI  - Do the suprasellar neurenteric cyst, the Rathke cleft cyst and the colloid cyst
      constitute a same entity?
AB  - Two cases of entirely suprasellar cysts are reported. Total surgical removal was
      performed in both cases. Pathological and immunohistochemical profiles were
      consistent with neurenteric cysts, Rathke's cleft cysts or colloid cysts and was
      also in keeping with an endodermal origin. It is now admitted that these three
      kinds of cysts share similar histological and immunohistological features. We
      propose an hypothesis of common embryological origin from endodermal remnants.

PMID- 8748763
TI  - Solitary cerebral metastases from intestinal carcinoma.
AB  - The authors report 34 cases of solitary cerebral metastases from intestinal
      cancer. In 24 cases the tumour was localized in the colonrectum and in 10 in the
      small intestine. In 8 patients (23%) neurological symptoms were the first
      clinical sign of systemic spread of the tumour; in 26 cases (77%) there was a
      long interval between treatment of the primary and appearance of the cerebral
      metastasis (average 24 months). Average survival was 10 months and was influenced
      solely by staging of the primary. Interestingly, the prognostic value of
      radiotherapy was minimal and none of the patients operated by the "no touch
      technique" presented with a recurrence.

PMID- 8748765
TI  - Evaluation of craniospinal system condition using standardized volume-pressure
      loadings.
AB  - Standardized volume-pressure craniospinal system loadings based on physiological
      loadings were developed in order to study the CSF outflow route efficiency and to
      evaluate the intracranial volume-pressure relations. The study was carried out on
      10 cats. Standardized abdominal compression was applied in order to produce a
      central venous pressure increased and subsequently ICP increase to the level of
      20 and 30 mmHg for 2 minutes. The abdominal compression test seems to be useful
      in the CSF outflow route evaluation. The orthostatic changes were studied in
      control animals and in cats with an epidural balloon. The animal body was
      evaluated to an angle of 50 degrees and 80 degrees with the head directed upwards
      and downwards. This test was found suitable for the intracranial volume reserve
      estimation. Similar application, especially in experimental conditions can be
      found in the hypercapnia test. PaCO2 concentration was increased by means of
      respiration with a gas mixture containing 5% CO2. A steady increase of ICP of 9
      +/- 1 mmHg was obtained. Vascular dilatation resulted in an intracranial volume
      loading. The ICP response in subjects with normal CO2 response can be related to
      the intracranial volume reserve. The studies performed show the usefulness of the
      standardized volume-pressure loadings. The loadings applied are more
      physiological than lumbar infusion tests used so far.

PMID- 8748764
TI  - Effects of vitamin D and retinoic acid on human glioblastoma cell lines.
AB  - The biological significance of vitamin D receptors expressed by glioblastoma and
      other glial tumours is still unclear. In an effort to clarify this issue we
      studied the effects of increasing concentrations of 25-dihydroxyvitamin D3 and
      its metabolite 1 alpha,25-dihydroxyvitamin D3 on two human glioblastoma cell
      lines. Both substances were capable of inducing a significant (> 50%) reduction
      in growth of the two glioblastoma cell lines at dosages over 5 microM. When the
      HU 70 cell line was treated by increasing dilutions of 25-dihydroxyvitamin D3
      combined with 1 microM all trans-retinoic acid, significant inhibition was
      apparent even after addition of 25-dihydroxyvitamin D3 in the nanomolar range.
      Reduction of growth index was mainly due to induced cell death. Our results
      provide in vitro evidence that vitamin D metabolites alone or in combination with
      retinoids may be potentially useful agents in the differentiation therapy of
      human malignant gliomas.

PMID- 8748766
TI  - Repair of anterior base of skull with free latissimus dorsi flap.
AB  - After craniofacial resection for ethmoid and nasal cancer the resulting defect in
      the anterior base of skull often is a problem because of liquorrhoea, followed by
      meningitis and brain herniation. Two approaches were used for surgery of ethmoid
      and nasal cancer involving the anterior base of skull-the transfrontal and the
      transethmoidal. The neurosurgeon performs the transfrontal approach, an
      additional lateral rhinotomy and ethmoidectomy is made by the ENT-surgeon. Seven
      patients underwent radical operation with immediate repair of the skull base
      defect performed in four and delayed repair in three cases with a microvascular
      latissimus dorsi muscle flap. The flap was tailored as a pure muscle transplant
      if only the base of skull had to be repaired and the surgical cavity had to be
      obliterated. In three cases a skin paddle was left on the muscle to perform
      closure of the orbit and of the hard palate. The aim of reconstruction is a good
      functional and cosmetic result and reduction of postoperative problems-such as
      brain herniation, CSF-leakage and meningitis-by obliteration of surgical
      cavities. Furthermore crusting of large cavities and disorders of phonation are
      reduced. The disadvantage of limited direct postoperative tumour control by nasal
      endoscopy however is justified by an increase of quality of life.

PMID- 8748767
TI  - Madreporic coral for cranial base reconstruction. 8 years experience.
AB  - The authors, since 1985, have used 587 Madreporic Coral grafts as bone substitute
      in a total of 183 patients, among them in 80 cases for repair of cranial base
      bone defects. They report their long-term results. Partial resorption to about
      40% of the initial volume occurred in almost all cases within 8 to 10 months,
      with complete resorption after about one year. 20% of the coral blocks moved
      spontaneously or split into pieces, but could easily be withdrawn rhinoscopically
      through the nostrils. No CSF leakage was noticed afterwards. The local infection
      rate was only 4%, always close to the basal coral graft. This is lower than the
      infection rate after using autologous bone harvested from the inner table of the
      bone flap (20%). Infections were cured by removal of the coral graft. Despite the
      mentioned draw backs, Madreporic Coral graft implants can be recommended as bone
      substitute in cranial base surgery: 1. The material simplifies the surgical
      procedure; 2. Harvesting of autologous bone is no longer necessary; 3.
      Transmission of infections like AIDS, Hepatitis C or Creutzfeld-Jacob-disease can
      be avoided with certainty.

PMID- 8748768
TI  - Frequent TIA in the territory fed by the anastomosed STA after combined
      therapeutic ICA occlusion and extracranial-intracranial bypass: case report.
AB  - Frequent transient ischaemic attacks (TIAs) in the territory fed by the
      anastomosed superficial temporal artery (STA) after combined therapeutic internal
      carotid artery (ICA) occlusion and extracranial-intracranial bypass is described
      in a 52-year-old woman with a giant aneurysm in the supraclinoid portion of the
      left ICA showing impairment of visual acuity in the left eye and right upper
      quadrantanopia. After the balloon test occlusion of the left ICA which was
      tolerated, the left STA-middle cerebral artery anastomosis was performed and
      occlusion of the left ICA using detachable balloons was carried out a day later.
      TIAs corresponding to the territory fed by the anastomosed STA occurred nine
      times two to four days and five times eight to nine days after the ICA occlusion
      without new infarction on computed tomography (CT) scan. Single-photon emission
      computed tomography showed no hypoperfusion immediately after the initial TIA. CT
      scan revealed thrombosis of half of the aneurysm a day after the ICA occlusion.
      The patient developed the same TIA as previously by compression of the left
      anastomosed STA at the time of follow-up angiography which was carried out eight
      days after the occlusion. Although heparin was continuously administered after
      the ICA occlusion for two days, the initial TIA occurred during heparinization.
      Anticoagulation seemed to be inadequate judging from activated coagulation time
      and incomplete thrombosis of the aneurysm occurred during heparinization. It is
      likely that the TIAs are caused by embolism via the STA, which is a rare
      ischaemic complication.

PMID- 8748769
TI  - Clinical experience with a new pressure-adjustable shunt valve.
AB  - The pressure-adjustable valve system Codman Medos allows valve pressure
      adjustment in 18 steps between 30 and 200 mm H2O. A series of 90 patients, 15
      children and 75 adults, who were shunted with this new programmable valve, is
      reported. Indication for shunt insertion were various types of hydrocephalus in
      79 cases, malfunction of a medium pressure membrane valve shunt system in 9 cases
      and an arachnoid cyst and pseudotumour each in one case. The valve pressure was
      programmed prior to insertion to 200 mm H2O in the adults and according to age in
      children and was modified postoperatively according to the clinical course.
      Underdrainage with subdural fluid collections appearing in 5 patients could be
      managed by valve pressure adjustment alone in 2 cases. One malfunctioning of the
      valve mechanism was due to mechanical obstruction. At the time of follow-up, 7 to
      29 months after operation, outcome was excellent in 64 patients, good with marked
      improvement but residual symptoms in 19 patients and unchanged in 7 patients. The
      possibility of adjusting the valve pressure to the patient's demands was
      frequently used in children and adult normal pressure hydrocephalus patients with
      satisfying clinical results.

PMID- 8748770
TI  - Cephaloceles - experience with 42 patients.
AB  - Forty-two patients with 44 cephaloceles treated between 1966 and 1993 are
      presented. Eighteen lesions were occipital, 2 parietal, 1 at the anterior
      fontanelle, 11 sincipital, and 12 basal. In recent years computerized tomography
      (CT) and magnetic resonance imaging (MRI) provided better information on the site
      and nature of the lesion as well as on associated malformations. Different
      malformations were associated more frequently with the cranial vault lesions.
      Cerebrospinal fluid (CSF)-rhinorrhea was the most frequent clinical sign in the
      basal lesions. Excision of the cele was performed in all but one case. The age at
      the time of surgical treatment ranged from 1 day to 11 years. Seven patients were
      shunted. Post-operative complications were persisting CSF-leaks in 5 patients
      needing operative revision and 2 infections. The outcome was good in the anterior
      lesions and in the occipital meningoceles.

PMID- 8748771
TI  - Surgical management of pineal region tumors.
AB  - The authors advocate an aggressive surgical approach to pineal region tumors to
      provide a definitive histological diagnosis and to facilitate extensive tumor
      removal. This strategy is based on their surgical experience in 160 operations
      for pineal region tumors in which operative mortality was 4% with 3% permanent
      major morbidity. One-third of pineal tumors were benign for which surgery alone
      was usually curative. A gross total removal was possible in 31 of 107 malignant
      tumors. The supracerebellar infratentorial approach was preferred in 86% of
      patients. The tumors displayed considerable histological diversity with germ cell
      tumors most common (37%), followed by glial cell tumors (28%) and pineal cell
      tumors (23%). Mixed tumors occurred 15% of the time. Spinal metastases were rare,
      occurring in less than 10% of patients with malignant tumors. These results with
      a large series of pineal region tumors demonstrate the safety and efficacy of
      aggressive pineal tumor surgery.

PMID- 8748772
TI  - Outcomes analysis in cranial base surgery - preliminary results.
AB  - A system of analysis addressing predictors of management outcomes in Cranial Base
      Surgery has yet to be published. We therefore report data on seventy-nine
      consecutive patients undergoing surgery for tumors involving the cranial base,
      excluding patients with the diagnosis of pituitary microadenoma. Outcomes were
      defined prospectively in terms of completeness of tumor resection, complications
      of treatment with emphasis on neurological morbidity, and return to work or
      independent living. Also, preoperative features are analyzed as influencing cost
      of treatment, estimated in terms of the number of surgical procedures required,
      duration of hospital and Intensive Care Unit stay, and time taken to return to
      work. Preliminary analysis of data reveals that severe brainstem compression,
      large tumor size (average diameter > 3 cm), high cavernous sinus grade, and tumor
      encasement of major cerebral arteries are associated with incomplete tumor
      resection (p < 0.05). Patient age greater than 65, preoperative Karnofsky
      Performance Score (KPS) less than 80, and severe brainstem compression are
      associated with increased risk of stroke (p < 0.05). Age greater than 65 and
      preoperative KPS less than 80 are associated with an increased length of stay (p
      < 0.05). Other untoward events did not occur with sufficient frequency to reach
      statistical significance. A model of outcomes analysis in Cranial Base Surgery is
      proposed utilizing a database to incorporate a group of non-operated patients and
      include quality of life measurements in long-term patient follow-up.

PMID- 8748773
TI  - The retrosigmoid approach to acoustic neurinomas: technical, strategic, and
      future concepts.
AB  - The retrosigmoid approach continues to be the most widely employed strategy for
      the surgical resection of acoustic neuromas. The results with respect to facial
      nerve function are uniformly reported to be quite high. The great emphasis
      currently is upon improving results with regard to the conservation of useful
      hearing. This paper focuses on the anatomical and strategic surgical factors that
      we currently consider to be important to maximizing our current results. The
      future aspects of this trend toward improved success in conserving hearing in
      these patients is also discussed.

PMID- 8748774
TI  - Acoustic neurinomas associated with vascular compression syndromes.
AB  - Trigeminal neuralgia and hemifacial spasm are caused by vascular compression of
      the cranial nerves at the brainstem in the majority of cases. Trigeminal
      neuralgia occurring in 3.3% of acoustic neurinomas is usually assumed to be a
      sign of large tumour size; if associated with small tumour size, an additional
      pathology, such as typical vascular compression must be suspected and has to be
      explored at surgery. While facial paresis will usually lead to immediate
      radiological diagnosis of a possible cerebellopontine angle (CPA) neoplasm,
      facial spasm is usually not expected to be associated with a CPA tumour. We
      report on clinical presentation, operative findings, surgical treatment and
      results in 9 cases of small acoustic neurinomas associated with trigeminal
      neuralgia and on 4 cases associated with hemifacial spasm. The importance of the
      clinical characteristics is stressed; if these are typical of a vascular
      compression syndrome, further exploration at the time of tumour surgery and
      specific treatment by vascular decompression are necessary.

PMID- 8748775
TI  - The far lateral-combined supra- and infratentorial approach: clinical experience.
AB  - Four patients underwent a far lateral-combined craniotomy procedure for extensive
      tumors of the clivus and craniocervical junction. Their presentation, operative,
      and clinical course are discussed. All patients had improved at their follow-up
      examination (mean follow-up, 10.7 months). This approach can now be applied to
      extensive tumors of the petroclival region and craniocervical junction to
      decrease morbidity.

PMID- 8748776
TI  - Failure in management of pituitary tumors discussion of 3 cases.
AB  - Three patients with pituitary adenomas (ACTH-secreting, non-secretory, and multi
      secretory) with unfavorable course, in spite of repeated microsurgery, drug
      therapy, as well as radiotherapy and radiosurgery, are presented. Each case was
      re-evaluated for possible flaws in management. Two of the invasive tumors
      continued to grow, in spite of correct management. The third patient with a
      pituitary adenoma underwent microsurgical resection, and later following a false
      positive finding of recurrence, received radiotherapy and underwent radiosurgery.
      The lesion actually was chronic inflammatory tissue.

PMID- 8748778
TI  - GDC-system embolization for brain aneurysms - location and follow-up.
AB  - GDC (Guglielmi detachable coil)-embolization for the treatment of brain aneurysms
      was first published by Guglielmi in 1991 and has become an integral part of the
      treatment strategy for cerebral aneurysms in many places around the world. Low
      morbidity and mortality rates are set against the limited possibilities of
      aneurysm neck occlusion, especially in large necked aneurysms. Depending on the
      architecture and on the kind of coil distribution, recanalization of the neck is
      more or less frequent. Nevertheless, rebleeding rates are low. In our series of
      211 brain aneurysms from March 1992 to June 1994, 74 (35%) patients underwent GDC
      embolization. 4 patients received combined treatment (GDC-embolization and
      subsequent surgery). Follow-up angiography was performed on 41 patients (55%) at
      periods of 6, 12, and 24 months (mean follow-up 8 months). To demonstrate the
      results in a graphic display, the aneurysms were grouped according to location
      and size. The analysis of the follow-up results shows the highest occlusion
      stability in aneurysms of the basilar tip, followed by aneurysms of the PICA
      origin, the basilar trunk and the PCA. Less stability was obtained in aneurysms
      of the PCom followed by MCA, Acom and aneurysms of the internal carotid (C1,
      ophthalmic). Aneurysms of the posterior circulation show generally better results
      than those located in the anterior circulation. This makes (in combination with
      the increased surgical difficulties of aneurysms in the posterior fossa) the GDC
      treatment especially useful for posterior circulation aneurysms.

PMID- 8748777
TI  - Gamma knife surgery for craniopharyngioma.
AB  - We present our results of Gamma Knife surgery for craniopharyngioma in nine
      patients. The current status of surgery, radiation therapy, intracavitary
      instillation of radionucleides and Gamma Knife surgery in the management of
      craniopharyngiomas is discussed.

PMID- 8748779
TI  - Endosaccular occlusion of basilar artery bifurcation aneurysms using electrically
      detachable coils.
AB  - Thirteen patients with basilar artery bifurcation aneurysms, treated by
      electrothrombosis using electrically detachable coils, are presented. Nine of
      them presented after hemorrhage, two with mass effect, and two were found
      coincidentally with other ruptured aneurysms. Selection for endovascular therapy
      was based on the following criteria: 1) poor clinical condition (Hunt and Hess
      III-V); 2) high surgical risk; 3) age and poor medical condition; 4)
      morphological features (small necked aneurysms). With endovascular Guglielmi
      detachable coils aneurysm occlusion ranging from 70-100% was achieved in all
      cases. All five small necked and two large broad necked aneurysms were totally
      occluded. Two large aneurysms had a 95% occlusion and two other large aneurysms
      were 90% occluded. In another patient with a large broad based aneurysm only an
      80% occlusion was achieved, because of tortuosity of the vertebrobasilar system.
      Our last patient, who presented as grade V clinically, was partially treated with
      a 70% aneurysmal occlusion. The clinical results were excellent in 10 and good in
      2. The only poor outcome was seen in the grade V patient. There was no morbidity
      or mortality related to therapy. The only complication was an asymptomatic
      dissecting aneurysm at the origin of the vertebral artery. Angiographic follow up
      time ranged from 6 to 20 months with a mean of 9 months. Four patients were
      treated too recently to have their angiographic follow up at 6 months. Two
      patients were lost to follow up. Clinical follow up ranged from 1 to 17 months
      with a mean of 8.9 months. The analysis of our cases clearly shows that
      aneurysms, which were densely packed with coils, especially if small necked, were
      less likely to be reperfused and showed a longlasting stable result. Large broad
      based aneurysms were more likely to be reopened by blood flow after the first
      procedure, especially if loosely filled with coils, and needed up to 3
      interventions to achieve a satisfying result, whereas later in the series a high
      percentage rate of occlusion was seen after the first procedure. We consider now
      also a less than 100% occlusion acceptable, because most of the aneurysms will
      rupture at the dome, which was occluded in all our cases. We conclude, that this
      new endovascular method is a viable alternative in the treatment of posterior
      circulation aneurysms with a high surgical risk, in old patients and those in
      poor clinical and medical condition.

PMID- 8748780
TI  - Endoscopically assisted microneurosurgery.
AB  - Technological developments in neuroendoscopy are leading to an expansion of
      applications into the realm of microneurosurgical procedures. The new dimension
      that using an endoscope provides requires insight into different neuroanatomical
      aspects and a new kind of strategy in planning a microneurosurgical procedure. To
      gain some new insights into these exciting aspects of neurosurgery we have
      explored the sellar, parasellar, and posterior fossa regions in 50 fresh
      anatomical specimens and used various types of endoscopes to observe the
      surgically relevant neurotopographical details. We then utilized this experience
      in 33 clinical cases during microsurgical approaches for various lesions
      (posterior fossa tumors - 12 cases, sellar and parasellar tumors - 8 cases, trans
      sphenoidal procedures for pituitary adenoma - 7 cases, transventricular
      procedures - 6 cases). In the laboratory we found that familiar neuroanatomical
      structures are seen in a completely different aspect from what we are accustomed.
      Orientation is at times difficult, which requires rehearsal and special handling
      of the endoscope for complex clinical procedures. We found that certain
      structures that are hardly noticed in routine anatomical views become very
      important when utilizing the endoscope (i.e., different arachnoid membranes and
      trabeculae). Importantly, the dimensions of a microsurgical approach can be
      greatly enlarged with the endoscope, making it possible to look behind structures
      and ''around corners''. We present our findings with respect to important
      anatomical details relevant to utilizing the endoscope as an adjunct to
      microneurosurgical procedures and our clinical data. We have concluded that the
      neuroendoscope can be a safe and helpful adjunct in many microneurosurgical
      procedures.

PMID- 8748781
TI  - Video-assisted endoscopic spinal surgery: thoracoscopic discectomy.
AB  - The use of new endoscopic techniques to conduct a thoracic discectomy is
      presented. The development of these endoscopic techniques through live porcine
      and cadaver models are outlined. It is concluded that the use of multiple ports
      for the endoscopic approach to the thoracic spine provides an exposure to the
      anterior and lateral spinal theca that is equal to the exposure afforded by the
      more extensive thoracotomy. Current techniques are being developed for
      transperitoneal and retroperitoneal endoscopic lumbar spine surgery.

PMID- 8748782
TI  - Cavernous angiomas of the spinal cord clinical presentation, surgical strategy,
      and postoperative results.
AB  - Nine consecutive cases of surgically treated spinal cavernous angiomas are
      presented. Our series consists of 6 men and 3 women with the following
      intramedullary spinal location of the cavernomas: 4 cervical, 4 thoracic and 1
      thoraco-lumbar. All 9 patients were symptomatic with signs of myelopathy and
      senorimotor deficits corresponding to the level of the lesion. Six patients
      underwent laminectomy and in three patients a hemilaminectomy was performed to
      approach the lesion. A complete resection of the cavernoma was achieved in each
      case. Five patients showed transient neurological deterioration, in three cases
      the neurological status remained unchanged, and one patient experienced a slight
      improvement of symptoms during the early postoperative period. At follow-up
      examination (mean 14 months postoperative), a clear improvement of the clinical
      signs was demonstrable in 6 patients, and a complete resolution of the pre
      existing symptoms and signs was achieved in two individuals. In one case the
      clinical state remained unchanged. It is concluded that microsurgical resection
      is the treatment of choice in cavernomas of the spinal cord.

PMID- 8748783
TI  - Microsurgical anterior decompression and internal fixation with iliac bone graft
      and titanium plates for treatment of cervical intervertebral disc herniation.
AB  - 42 cervical interbody fusions with iliac bone graft and titanium plate fixation
      were performed between October 1991 and March 1994. The mean follow up period in
      this study was 10.7 months. In 32 cases fusion was done for 1 and in 10 cases for
      2 segments. 2 different types of plates were used. In 25 cases micro
      osteosynthesis plates and screws with 2.7 mm diameter were used, and in 17 cases
      cervical H-plates and screws with 3.5 mm diameter. A favourable outcome was
      achieved in 31 of 42 cases (74%). Satisfactory pain relief was achieved in 90%.
      For radicular motor deficit good results were obtained in 84% and for cervical
      myelopathy in 54%. The 2 different types of plates showed a remarkable difference
      in the clinical outcome. The results were regarded favourable in 15 of 25
      microplate fusions (60%) and in 16 of 17 H-plate fusions (94%). Compression of
      the bone graft was seen in 5 patients of the micro plate group, however,
      radiological signs for fusion were present in all 42 cases at follow up. Major
      surgical complications, damage to neural structures or neurological deterioration
      did not occur in this study. Plate fixation in cervical interbody fusions seems
      to be a safe procedure and may reduce graft related complications at the fusion
      site if the plates and screws are sufficiently well proportioned. A favourable
      impact upon the results for cervical interbody fusion might be expected and
      should be further investigated in a long term follow up study.

PMID- 8748784
TI  - Diagnostic value of stereotactic biopsy of cerebral lesions in patients with
      AIDS.
AB  - A neurological complication occurs in 40-60% of HIV infected patients during the
      course of the disease. In 10-20% the neurological complication is the first
      manifestation of the HIV infection. A reliable neuropathological diagnosis is a
      prerequisite for a specifically selected treatment. While modern computer
      assisted imaging techniques, such as computed tomography or magnetic resonance
      imaging, do possess a high sensitivity, they do not as a rule permit an
      unambiguous diagnosis. Between October 1989 and July 1994 we biopsied 38 HIV
      infected patients stereotactically. The indication for the biopsy was determined
      by having radiologically detectable lesions with no regression tendency in
      patients under antitoxoplasmosis therapy. In 89% an unambiguous diagnosis was
      made based on the biopsy; 11% of the biopsies were not diagnostic. For the most
      part, toxoplasmosis (31%) and progressive multifocal leucoencephalopathy (29%)
      were involved. 18% of the patients suffered from a non-Hodgkin lymphoma. The foci
      were primarily frontal (47%), parietal (21%) or localised in the basal ganglia
      area (11%). The result of the biopsy led to a change in treatment for 52% of the
      patients. Morbidity and mortality of the operation were 0%. The results or our
      research series are similar to other groups. It was shown that stereotactic brain
      biopsy is a safe and effective method for establishing a sound basis for treating
      the frequently life-threatening cerebral complications of AIDS.

PMID- 8748785
TI  - On the principles underlying the diagnosis of brain tumours--a survey article.
AB  - A survey is given of the principles underlying the diagnosis of brain tumours.
      Traditionally diagnosis and localization of brain tumours have been based upon
      morphological criteria. Currently unsurpassed levels in imaging of anatomical
      details and topographical relations by the techniques of computed tomography (CT)
      and magnetic resonance imaging (MRI) have been achieved. The techniques of
      positron emission tomography (PET) and of magnetic resonance spectroscopy (MRS),
      which depict also metabolic and blood flow aspects, provide a refinement of our
      knowledge on the metabolism, structure and pathophysiological relations of a
      tumour to the surrounding parenchyma. Recent advances in the recording of
      function-related changes of the cerebral electro-magnetic field allow a better
      definition of critical functional areas.

PMID- 8748786
TI  - Correlation of fornix damage with memory impairment in six cases of colloid cyst
      removal.
AB  - We studied six patients in whom colloid cysts had been removed surgically from
      the third ventricle. The patients were selected simply by availability for the
      study, not on grounds of clinically diagnosed amnesia or its absence. The
      outcomes of operation ranged from one patient who had postoperatively resumed a
      normal life without complaint of memory disorder at any stage, through four who
      complained of memory disorder since operation, to one who was so severely amnesic
      as to require constant supervision. Each patient was given psychometric tests of
      memory, and was also scanned by magnetic-resonance imaging. One of us examined
      the six scans and assessed the extent of damage to the fornix, and any other
      brain damage, in ignorance of the outcomes of the psychometric tests. The fornix
      in the right hemisphere had been destroyed in all six cases, and all showed
      evidence of moderate or severe impairment in nonverbal memory. The fornix in the
      left hemisphere was intact in only one patient; this was the patient who had
      resumed a normal life without complaint of memory disorder. The left fornix was
      damaged with some sparing in one further patient, and the remaining four patients
      showed destruction of the fornix in the left as well as in the right hemisphere.
      The severity of impairment in verbal memory in these six cases was related to the
      severity of the damage to the left fornix. No other evidence of brain damage
      appeared to be systematically related to memory ability. These results add to the
      evidence that bilateral fornix damage produces amnesia, and that sparing of the
      left fornix alone is sufficient to ensure a more favourable outcome.

PMID- 8748787
TI  - Seizures in patients with supratentorial oligodendroglial tumours.
      Clinicopathological features and management considerations.
AB  - In this study of 34 consecutive histologically confirmed oligodendroglial brain
      tumours (15 oligoastrocytoma, 12 oligodendroglioma, 7 anaplastic
      oligodendroglioma) twenty five patients (75%) presented with symptoms related to
      seizures. Although the seizure incidence was lowest in anaplastic
      oligodendroglioma (57%) it was not statistically different from either pure (75%)
      or mixed (80%) oligodendroglial tumours. Patients with seizures had a
      significantly lower age (p < 0.001) at diagnosis (median 36 years) than those
      without seizures (57 years). The types of seizure disorder, that were present for
      a median of 15 months prior to surgery, were variable with 32% having
      generalised, 36% partial and 32% mixed patterns. There were no significant
      differences between either the type or incidence of seizures and the particular
      cerebral location of the oligodendroglial tumour. Twenty four of the patients
      presenting with seizures underwent surgery (5 stereotactic biopsy, 5 stereotactic
      guided resection and 14 conventional craniotomy and resection) without
      intraoperative electrocorticography (ECoG). Eighteen (75%) of these patients also
      had postoperative radiotherapy (40 to 54 Gy in 30 fractions. Following these
      treatments the percentage of patients fit free at 6, 12, and 24 months were 67%,
      56%, and 53%, respectively. Median time to first post operative seizure was 32
      weeks (range 5 weeks to 5.3 years). After a median follow up time of 30 months 20
      of the 25 patients who presented with seizures were still alive. Eight (40%) were
      seizure free and three other patients (15%) had experienced less than three
      postoperative seizures in follow-up periods ranging from 42 to 62 months.
      Although the numbers of patients on preoperative (87%) and postoperative (83%)
      anticonvulsant medications were similar, some had their medications either
      withdrawn (17%) or reduced (4%) whilst others had it introduced (12%) after
      interventional management. Only five (20%) patients who presented with seizures,
      compared to 6 (67%) who had not presented with seizures had died during median
      follow-up of 28 months. Three of nine patients (33%), who were initially seizure
      free, developed seizures between 25 and 36 months after initial surgery and
      radiotherapy. This study (i) confirms the high incidence of epilepsy in
      supratentorial oligodendroglial tumours; (ii) has shown that seizures associated
      with these tumours are significantly more common in younger patients; (iii)
      suggests that younger age, but not the presence of seizures, is a significant
      independent prognostic variable; (iv) that seizure control following a second
      operation is generally disappointing and (v) suggests that tumour resection and
      radiotherapy often facilitate control of the seizures by anticonvulsants. Because
      of the multiple clinicopathological and management variables involved a
      prospective study would be required to assess the optimal management of patients
      with seizure disorders associated with oligodendroglial brain tumours.

PMID- 8748788
TI  - Occipito-cervical fixation in rheumatoid arthritis--an analysis of surgical risk
      factors in 163 patients.
AB  - 163 patients with rheumatoid arthritis (RA) and atlanto-axial subluxation treated
      by posterior occipito-cervical fixation (OCF) over a period of twenty-one years
      (November 1970-January 1991) were followed. Common complaints prior to surgery
      were occipital headache, neck pain, radicular pain and myelopathy. The mean age
      at time of surgery was 61 years. The mean follow-up time was 54 months. Clinical
      improvement was obtained in 88% of the patients, whereas 7% were unchanged and 5%
      had progressive symptoms in spite of surgery. There was no pre-operative or
      immediate postoperative mortality. In 79 patients, one or more potential surgical
      risk factors were identified. Twenty-four reoperations were performed in the
      neck. The most common cause for reoperation was mechanical failure due to wire
      break or spinous process fracture. Wound infection in the neck was recorded in 16
      patients. Five were deep and required removal of the fixation material. Following
      OCF, new or progressive subaxial subluxation (SAS) led to further surgery in 4%.
      The study offers support for the beneficial effect of OCF in rheumatoid AAS. We
      conclude that, in spite of a number of identified risk factors, OCF with the
      Brattstrom-Granholm technique remains a safe and effective method for
      stabilization of upper cervical subluxations in RA.

PMID- 8748789
TI  - Acute traumatic posterior fossa subdural haematomas.
AB  - Acute Posterior Fossa Subdural Haematoma (PFSDH) caused by trauma is a clinical
      rarity: only 13 cases have been encountered in the literature. Three consecutive
      personal cases of PFSDH are presented. Two of them are respectively the sixth and
      the seventh surgically treated cases with success. Among the 16 cases 60% had a
      sudden clinical worsening within 24 hours. Seven cases had an occipital fracture.
      Of the thirteen cases operated upon 11 (85%) were in a state of deep coma. The
      surgical mortality was 46%. One patient had a good recovery (Grade 5) and six a
      moderate disability (Grade 4) on the Glasgow Outcome Scale. We conclude that
      surgical treatment must always be carried out even in patients presenting in an
      agonal state.

PMID- 8748790
TI  - Criteria for conservative treatment of supratentorial acute subdural haematomas.
AB  - Without mortality, 31 patients underwent conservative treatment for traumatic
      supratentorial acute subdural haematoma (SDH). Later on six of them had the
      haematoma surgically evacuated mainly because of a deterioration of the Glasgow
      Coma Scale (GCS) scores. It was found that patients with a midline shift of less
      than 10 mm on the computed tomography (CT) scans and with a GCS score of 15
      initially might be treated conservatively under close observation, reserving
      urgent craniotomy and evacuation of the SDH for those with deteriorating
      neurological conditions. A smaller degree of midline shift was tolerated by
      patients with an GCS score of less than 15: a shift of more than 5 mm on the
      initial CT scans predicted an exhaustion of the cerebral compensatory mechanism
      within 3 days of injury. In such cases the GCS score worsened, and surgical
      evacuation of the SDH became necessary. A total hospital stay of 6 to 7 days may
      suffice for those who have become fully conscious. Repeat CT studies before
      discharge should be done and a close follow-up during the first 3 to 4 weeks is
      advisable.

PMID- 8748791
TI  - Spinal dural arteriovenous fistulas: a plea for neurosurgical treatment.
AB  - Spinal dural arteriovenous fistulas are the most common type of arteriovenous
      malformation involving the spinal cord, especially in middle-aged men. We report
      21 patients with this malformation who had signs and symptoms of myelopathy. The
      diagnosis was established by selective spinal angiography in patients whose
      neurological deficits, myelograms or magnetic resonance tomographies suggested
      the presence of a spinal arteriovenous fistula. They were treated by
      microsurgical coagulation of the fistula nidus located in the dura and intradural
      division of the draining vein. Twenty patients improved neurologically following
      surgery, one remained unchanged. Complete obliteration of all lesions was
      verified by intra-operative microvascular Doppler sonography and in 3 cases by
      postoperative angiography. There were only a few minor and transient
      complications after surgery: one neurological deterioration where venous
      thrombosis was suspected, one cerebrospinal fluid accumulation and, in one case a
      transient wound healing impairment. Two patients had to be operated on again. In
      one case with difficult localization of a fistula at the L5/S1 level, the fistula
      was still visible in the postoperative angiogram. In another patient, a spinal
      epidural haematoma occurred a few hours after surgery. We conclude that
      microsurgical treatment of spinal dural arteriovenous fistulas is a safe, fast,
      simple and effective method of treating these lesions. However, recovery after
      surgical management was often incomplete because the diagnosis was established
      too late and the patient already presented with severe and long-lasting deficit.
      Thus, the main problem remains a diagnostic and not a surgical one.

PMID- 8748792
TI  - Primary spinal malignant schwannomas: clinical and prognostic remarks.
AB  - Malignant peripheral nerve sheath spinal tumours are relatively rare. A primary
      spinal location at onset from the nerve roots is rarely reported in the
      literature, thus the clinical features and therapeutic results of these spinal
      malignant tumours are not defined. Six cases of malignant primary spinal
      schwannomas, 2% of 293 spinal schwannomas operated on in a 38 year period, are
      reported. Based on an analysis of a limited number of cases, ours and those
      collected from the literature (21 patients), some suggestions are possible: a)
      pre-operative clinical presentation and imaging studies are not predictive of
      malignancy; b) postoperative outcome is poor, especially in patients with von
      Recklinghausen's disease and after partial removal of the tumour; c) local
      recurrence and metastases are possible, even after radical surgery and
      radiotherapy.

PMID- 8748793
TI  - Somatosensory evoked potential. Monitoring during spinal surgery.
AB  - Somatosensory evoked potentials (SSEPs) have been used to help minimize
      neurologic morbidity during spinal surgery. While this is a sensory test it has
      been used as an inference of motor function. The failure to always achieve the
      latter goal has resulted in some pessimism regarding the value of this test. In
      this series of 161 operations in 150 patients, it was demonstrated that SSEPs
      were recordable under anesthesia in 87% of patients. Of these patients, 12% had
      their spinal surgery interrupted due to significant neurophysiologic changes; of
      these patients, 18% had new neurologic deficits postoperatively. There were no
      cases with new neurologic deficits who had no changes in their SSEPs. It was
      concluded that SSEP monitoring may be helpful in identifying potentially
      neurologically threatening surgical maneuvers in a significant number of
      patients.

PMID- 8748794
TI  - The influence of total body hyperthermia on brain haemodynamics and blood-brain
      barrier in dogs.
AB  - This study was designed to examine the influence of total body hyperthermia
      (TBHT) using an extracorporeal circuit with a heat exchanger on the cerebral
      blood flow (CBF), intracranial pressure (ICP), brain tissue pH, cerebral
      autoregulation and blood-brain barrier (BBB) permeability in dogs. The rectal
      temperature of the dow was raised to 41.5 degrees C, maintained at 41.5-42.0
      degrees C for 2 hours (HT period) and then reduced to normothermia by cooling.
      Regional CBF was measured by the hydrogen clearance method before heating, during
      the HT period and after cooling. ICP and brain tissue pH were monitored during
      the TBHT treatment. Autoregulation of the CBF during the HT period was assessed
      by measuring the regional CBF and the ICP in a state of induced hypo- or
      hypertension. The influence of TBHT on BBB permeability was examined using an
      immunohistochemical technique. The regional CBF increased from 38.1 +/- 6.5 (mean
      +/- SD) to 49.1 +/- 9.8 ml/100 g/min and the ICP from 10.3 +/- 4.2 to 16.8 +/-
      3.4 mmHg when TBHT was raised. These returned to normal values after cooling. The
      regional CBF and the ICP changed in parallel with drug-induced changes of mean
      arterial blood pressure during the HT period. These changes suggest that
      autoregulation of the CBF is paralysed during the HT period. Brain tissue pH
      decreased rapidly when the rectal temperature exceeded 41.0 degrees C. The pH was
      7.18 +/- 0.05 during the HT period and was relatively stable. The pH returned to
      a normal value after cooling. Immunopositive stain for albumin was not observed
      in heated brain tissue except for the normally leaky pineal gland and the choroid
      plexus, indicating preservation of BBB during TBHT. These results suggest that
      brain oedema may occur easily due to paralysed cerebral autoregulation when the
      arterial blood pressure fluctuates excessively, so arterial blood pressure must
      be controlled strictly during TBHT.

PMID- 8748795
TI  - Measurement of regional cerebral blood flow with H2(15)O positron emission
      tomography during Matas test. Report of three cases.
AB  - The authors carried out a Matas test with a regional cerebral blood flow (rCBF)
      study using H2(15)O positron emission tomography (PET) for three cases of large
      internal carotid artery aneurysms. There is a likely correlation between the
      cerebral blood flow (CBF) reduction rate obtained by PET, and the mean stump
      pressure available from a conventional balloon occlusion test. The advantages of
      this noninvasive and quantitative method are presented in comparison with other
      methods.

PMID- 8748796
TI  - Extended middle fossa approach for petroclival lesions.
AB  - A modification of the previously described transcochlear approach to extra- and
      intradural petroclival and clival lesions is described in this report. It is an
      approach from the middle cranial fossa. It involves unroofing and depression of
      the external ear canal, removal of the glenoid cavity of the temporo-mandibular
      joint, exentration of the middle ear ossicles, posterior mobilization of
      labryrinthine and tympanic segments of the facial nerve, and drilling of the
      petrous bone from an entirely lateral perspective. An extensive and low exposure
      of the petroclival region, posterior aspect of the cavernous sinus, upper and mid
      clivus and the cerebellopontine angle is obtained. The anterior surface of the
      brain stem upto the pontomedullary junction is exposed with minimal or no
      retraction of the temporal lobe of the brain. The vein of Labbe and sigmoid sinus
      drainage is unhampered. Anterior and posterior extension of the exposure is
      possible. Only a limited mastoidectomy and labyrinthectomy, necessary to
      facilitate exposure and mobilization of the facial nerve is necessary. The
      inferior limit of the exposure is set by the dome of the jugular bulb. Hearing is
      sacrificed. The technique and merits of the procedure are discussed in this
      report. The study is based on surgical experience of 4 cases.

PMID- 8748797
TI  - Shaving the hair--is it always necessary for cranial neurosurgical procedures?
AB  - Shaving of the hair and neurosurgical procedures are almost inseparably connected
      issues. This may add an additional psychological stress to the patient. Those
      departments which abandoned pre-operative shaving did not see higher infection
      rates. From January 1993 to September 1994 we performed 57 cranial procedures
      without any shaving, among them 5 shunt procedures. We found no disturbances of
      wound healing or septic complications. Therefore neurosurgical procedures without
      shaving are recommended for all benign cranial processes if a rapid
      rehabilitation of the patient to his normal daily life is to be expected.

PMID- 8748798
TI  - Astrocytoma linked to familial ataxia-telangiectasia.
AB  - A 7-year and 11 month-old girl with cerebellar astrocytoma linked to familial
      ataxia-telangiectasia (AT) is presented. She was born as the 7th girl of a woman
      with aortic arch syndrome. Two elder sisters of the patient have ataxia
      telangiectasia. She had immunodeficiency, and cerebellar ataxia, but had no
      oculocutaneous telangiectasia. The risk of cancer developing in AT patients is
      about 1,200 times greater than that in age-matched controls. With regard to
      central nervous system tumours, seven primary tumours have been reported, such as
      3 cases of medulloblastoma and 4 cases of glioma. Members of AT families who were
      under the age of 45 had a risk of dying of a malignant neoplasm five times
      greater than in the general population. However, there were no reports of glioma
      in AT families. In this case, it is suggested that IgA deficiency linked to
      familial AT may have contributed to the development of astrocytoma.

PMID- 8748800
TI  - Solitary plasmacytoma of the spine: relationship of IGM to tumour progression and
      recurrence.
AB  - The authors report a retrospective study of 15 patients with solitary vertebral
      plasmacytoma. 15 patients were considered in this study on the basis of the
      following characteristics: 1) histologically confirmed plasmacytoma following
      surgical removal; 2) existence of a single vertebral lesion, documented by
      skeletal and MRI scan; 3) no signs, at diagnosis of disseminated disease by blood
      laboratory test, urine analysis, sternal puncture, iliac bone marrow biopsy, a
      total-body CT scan. The clinical course of the patients has been analysed on the
      basis of the following factors: age, sex, length of clinical history before
      diagnosis, site, presence/absence of the M component. The M component is an
      electrophoretically homogeneous immunoglobin. The most significant factors for
      predicting development of multiple myeloma proved to be the presence /absence of
      the M component at diagnosis and, to a lesser degree, the age of the patient. In
      the light of other reports too, it would seem that the presence of the M
      component at diagnosis is a reflection of aggressive biological and clinical
      tumour behaviour.

PMID- 8748799
TI  - Anterior decompressive microsurgery and osteosynthesis for the treatment of multi
      segmental cervical spondylosis. Pathophysiological considerations, surgical
      indication, results and complications: a survey.
AB  - Surgical treatment of cervical myelopathy due to multi-segmental cervical
      spondylosis (MSCS) is currently performed by either anterior or posterior
      approaches. Considering the complex nature of the underlying disease involving
      more than one cervical segment, as well as the patho-biomechanical features of
      the spondylotic cervical spine, adequate decompression of the spinal cord and
      correction of hypermobility should be achieved by surgery in one stage, in order
      to achieve positive immediate and long-term benefit for the patient suffering
      from progressive myelopathy. Recently, anterior decompressive surgery, consisting
      of single or multi-level vertebrectomy, microsurgical epidural decompression and
      osteo-synthesis has emerged as an aggressive therapeutic approach for the
      treatment of MSCS. Based on the experience of a series of 92 patients with
      progressive cervical myelopathy due to MSCS operated on using the above described
      combined techniques, as well as the results from a limited number of clinical
      studies of anterior decompressive surgery in MSCS patients from the literature,
      the pathophysiological considerations, surgical indications, surgical technique
      as well as clinical results and complications of anterior surgery in patients
      with MSCS are reviewed and discussed.

PMID- 8748801
TI  - Crowned dens syndrome: a manifestation of hydroxy-apatite rheumatism.
AB  - Crowned dens syndrome is defined as an association of acute cervical pain and
      calcifications in the peri-odontoid space. The authors report one case of this
      rare localization of hydroxy-apatite rheumatism and review 12 similar cases in
      the literature. This disease affects only adult females. Patients present with
      inflammatory signs, can be treated with non-steroid anti-inflammatory drugs and
      recover without sequela. Calcium pyrophosphate dihydrate deposition can also lead
      to this syndrome. Other perioodontoid calcifications and ossifications, usually
      asymptomatic, appear only as a radiologically crowned dens.

PMID- 8748802
TI  - CT and clinical criteria for conservative treatment of supratentorial traumatic
      intracerebral haematomas.
AB  - In search of guidelines for the management of traumatic intracerebral haematomas
      (TICHs) with slight mass effects on computed tomography (CT) scans, the author
      reviewed the records of 29 patients who did not undergo surgery and 11 patients
      who did. It is found that patients with a TICH volume of less than 15 ml, a
      midline shift of less than 5 mm, an open perimesencephalic cistern on CT scans, a
      Glasgow Coma Scale (GCS) score of 12 or more, and an absence of lateralizing
      signs may be treated conservatively and expected to make a good recovery. On the
      other hand, with zero mortality and satisfactory outcomes, the patients under
      going early surgery tended to have a TICH volume of more than 15 ml, a midline
      shift of more than 5 mm, an obliterated perimesencephalic cistern on CT scans, a
      GCS score of less than 12, and the presence of lateralizing signs. However, the
      position of such features as the criteria of early operation for a TICH is
      weakened by the retrospective nature of this study because some surgical
      patients, free of lateralizing signs in particular, might have managed to do well
      without craniotomy.

PMID- 8748803
TI  - Relative risk of deterioration after mild closed head injury.
AB  - In this prospective study, a series of 1812 consecutive mild head injured adult
      patients who visited the hospital emergency department were assessed. Twenty
      eight patients (1.5%) deteriorated after head injury; 23 of these (1.3% of the
      series) required surgical intervention. Five patients (0.3%) deteriorated due to
      non-surgical causes [post-traumatic seizure 2, syndrome of inappropriate
      secretion of antidiuretic hormone (SIADH) 3]. Most of the deterioration occurred
      within the first 24 hours (57%). Post-traumatic headache was found in 280
      patients (15.5%) and 84 patients (4.6%) suffered post-traumatic vomiting. The
      relative risk is calculated. Age over 60, presence of drowsiness, focal motor
      weakness, post-traumatic headache and vomiting has increased risk of
      deterioration (p < 0.001). This study suggests that post-traumatic headache and
      vomiting deserve more clinical attention rather than being considered as post
      traumatic syndrome only.

PMID- 8748804
TI  - The significance of neuron specific enolase levels in cerebrospinal fluid and
      serum after experimental traumatic brain damage.
AB  - In the posttraumatic period, measurement of neural tissue enzymes in serum and
      cerebrospinal fluid gives quantitative information about the severity of the head
      injury. In our study, we evaluated the relationship between the serum and
      cerebrospinal fluid levels of neuron specific enolase and the severity of trauma.
      Head traumas at different severity were applied experimentally (Mild 0.038 N,
      Moderate 0.057 N, Severe 0.3 N). Serum and cerebrospinal fluid levels of neuron
      specific enolase were measured in trauma and control groups of rats. Only in the
      severe trauma group, the neuron specific enolase levels of cerebrospinal fluid
      were significantly increased. There was no statistically significant difference
      between the groups when serum neuron specific enolase levels were evaluated. Our
      data leads us to conclude that trauma, causing significant neural damage, results
      in an increase in cerebrospinal fluid neuron specific enolase levels, however the
      serum neuron specific enolase levels do not seem to run parallel with that
      increase.

PMID- 8748805
TI  - Primary large choroid plexus papillomas in the cerebellopontine angle:
      radiological manifestations and surgical management.
AB  - Two cases of primary choroid plexus papilloma originating in the cerebellopontine
      angle (CPA) are reported. Both papillomas were encapsulated and strongly adhering
      to a choroid plexus tuft protruding from the foramen of Luschka. Successful
      removal of the tumour was achieved in each case. Surgical strategy,
      neuroradiological manifestations, and the differential diagnosis are discussed.

PMID- 8748806
TI  - Symptomatic salivary-rest cyst of the sella turcica.
AB  - Although ectopic salivary tissue in the posterior pituitary is frequently
      observed in microscopic examination at autopsy, this tissue is considered
      clinically insignificant. The authors report a case of sella turcica mass causing
      progressive menstrual irregularities and mild hyperprolactinemia in a 22-year-old
      woman. Magnetic resonance imaging revealed a 1.2 x 0.9 cm non-enhancing mass of
      the postero-inferior sella turcica. The lesion was isointense to brain on T1
      weighted images and hypo- to iso-intense on T2-weighted images. Transsphenoidal
      exploration revealed that the cyst wall consisted entirely of normal appearing
      salivary gland. The clinical, radiographic, and pathologic features of this
      unique entity are discussed.

PMID- 8748807
TI  - Tinnitus and hearing loss in pineal region tumours.
AB  - The authors report an underestimated symptom and sign arising in pineal region
      tumours: tinnitus and hearing loss. It has been observed in 13 out of 72 pineal
      region tumours (18%). Three illustrative cases are reported in this paper. The
      inferior colliculi, the structure more dense in fibres than any other auditory
      brain stem site and at which majority of the acoustic pathways relay, is closely
      adjacent to the pineal body. Displacement of this structure may be responsible
      for acoustic symptoms together with common visual symptoms.

PMID- 8748808
TI  - Intralesional administration of I-131 labelled monoclonal antibodies in the
      treatment of malignant gliomas.
AB  - The authors report their preliminary experience with the use of radiolabelled
      monoclonal antibodies (MAb) as an adjuvant treatment for 33 malignant gliomas.
      MAbs employed in this study are raised against Tenascin (TN) which is an antigen
      of the extracellular matrix of the tumour. It has also been found in neoplastic
      cells but never in normal brain tissue. This therapy is aimed to give a local
      high dose radiation (boost) while sparing healthy brain structures. This
      treatment has always been well tolerated and no adverse reactions at the level of
      CNS or major extraneural organs has been observed. Significant improvement of
      median survival has been obtained but this result should be cautiously evaluate
      since the study is non-randomized. Comparison with other current adjuvant
      technique is briefly discussed.

PMID- 8748809
TI  - Anaplastic ependymomas: clinical features and tumour suppressor gene p53
      analysis.
AB  - We analyzed seven cases of anaplastic ependymoma, focusing on neuro-imaging,
      histopathology, and mutations of the tumour suppressor gene p53. Five of the
      seven tumours were supratentorial. All had both cystic and solid components, with
      fragment calcifications detectable on CT scan. The solid parts of the tumours
      were imaged as heterogenous hypo- or iso-intense areas with moderate enhancement
      on T1-weighted magnetic resonance images. Vascularity was not prominent on
      angiograms except for one case. Histologically, in addition to the WHO criteria,
      loss of typical cellular architecture, endothelial proliferation, and necrosis
      were commonly found. A mutation in Exon 5 of the tumour suppressor gene p53 was
      detected in one anaplastic ependymoma out of five tumours (two benign and three
      anaplastic ependymomas) examined by PCR-SSPC analysis of genomic DNA followed by
      direct sequencing. Anaplastic ependymoma typically presents as a calcified cystic
      tumour in the supratentorial parenchyma or transependyma. Mutations of p53
      deserve further investigation to examine their possible role in the oncogenesis
      and malignant transformation of ependymoma.

PMID- 8748810
TI  - Atypical and anaplastic meningiomas--does the new WHO-classification of brain
      tumours affect the indication for postoperative irradiation?
AB  - We retrospectively analysed 13 patients (pts.) treated at the University of
      Tubingen from 1985 to 1993 to evaluate the results of radiation therapy (XRT)
      given as an adjuvant to totally or subtotally resected meningiomas. The overall
      survival was 38% at five years with a probability of relapse of 50% at this time.
      Reclassification of the tumours according to the new WHO-classification of brain
      tumours [14] revealed 10 grade-II-tumours (atypical meningioma) and 3 grade-III
      tumours (anaplastic meningioma). Radiotherapy failed in all 3 pts. with
      macroscopically incomplete resection (Simpson's grade IV), who died with relapse
      between 4 and 51 months after radiotherapy. 5 out of 10 pts. with grade-II
      tumours relapsed. All 3 pts. with grade-III-tumours died with relapse between 6
      and 21 months after XRT. Morbidity was seen in 2 pts. after irradiation with 60
      GY (ICRU dose specification). Complete surgical exstirpation offers the best
      possibility of tumour control. Grade-III-tumours should be irradiated whatever
      the extent of the primary surgery was. Our results might indicate a possible
      indication for XRT in pts. with atypical grade-II-tumours especially when radical
      surgery must be in doubt. Prospective multicentre trials are warranted to prove
      the prognostic value of the new WHO-classification for atypical and anaplastic
      meningiomas and to define the ultimate role of radiotherapy in this setting.

PMID- 8748811
TI  - The haemodynamic effect of transcranial Doppler-guided high-dose nimodipine
      treatment in established vasospasm after subarachnoid haemorrhage.
AB  - Eleven patients (7 females) with aneurysmal subarachnoid haemorrhage (SAH) and
      transcranial Doppler (TCD) signs of vasospasm during prophylactic intravenous
      nimodipine treatment (2 mg/h) were treated with TCD-guided high-dose (4 mg/h)
      intravenous nimodipine. The patients were followed clinically and with serial TCD
      investigations. Increasing nimodipine to high-dose treatment led to a reduction
      of the abnormally elevated mean flow velocities (FV) in all patients. There was
      also a reversal of clinical signs of delayed ischaemia. In one patient, repeated
      computer tomographic (CT) investigations revealed a reversal of ischaemic
      changes. Reduction of nimodipine from 4 to 2 mg/hr resulted in a return to
      abnormally elevated mean FV as well as a return of clinical signs of cerebral
      ischaemia. The outcome was favourable in 82% of the patients and there was no
      mortality or vegetative survival. No patient deteriorated clinically due to
      vasospasm during treatment with high-dose nimodipine. The individual effect of
      nimodipine treatment can be monitored by the use of serial TCD investigations.
      TCD-guided high-dose nimodipine treatment appears to be an effective treatment in
      SAH patients developing vasospasm despite prophylactic standard dose treatment.
      The data give support for a direct vascular effect of nimodipine on cerebral
      vasospasm.

PMID- 8748812
TI  - Intra-arterial infusion of papaverine combined with intravenous administration of
      high-dose nicardipine for cerebral vasospasm.
AB  - The clinical effect of combination therapy with high doses of intravenous
      nicardipine and intra-arterial infusion of papaverine on symptomatic vasospasm
      after subarachnoid haemorrhage (SAH) was analysed retrospectively. In 66 of 122
      patients who underwent early aneurysm surgery between 1990 and 1993, the
      intracranial haemodynamics were documented by transcranial Doppler (TCD)
      ultrasonography. 33 of these 66 patients received high dose nicardipine
      intravenously (Group I); the other 33 patients were not treated with calcium
      antagonists (Group II). Symptomatic vasospasm occurred in 6 Group I patients
      (18%) and in 13 (39%) in Group II patients. All 19 symptomatic patients received
      an intra-arterial infusion of papaverine; 15 patients (79%) responded well to
      this therapy and the symptoms were reversed quickly. Although the mean flow
      velocity (MFV) was not different between the two groups, it was reduced
      significantly after papverine infusion. Our retrospective analysis suggests that
      symptomatic vasospasm can be treated effectively with the combination of
      intravenous high dose nicardipine and intra-arterial infusion of papaverine, and
      that the correct timing of the infusions is crucial.

PMID- 8748813
TI  - Anti-phospholipid antibodies and cerebral vasospasm following subarachnoid
      haemorrhage.
AB  - Delayed ischaemic deficits due to cerebral vasospasm contribute to the high
      morbidity and mortality rates associated with subarachnoid haemorrhage. We
      evaluated the usefulness of measuring anti-phospholipid antibodies (aPLs) for
      prediction of the occurrence of symptomatic vasospasm and the outcome after
      subarachnoid haemorrhage. 32 consecutive patients with subarachnoid haemorrhage
      due to ruptured cerebral aneurysms were studied. They were admitted and operated
      on within 72 hours after the onset of subarachnoid haemorrhage. aPLs such as
      lupus anticoagulants, anti-cardiolipin IgG and anti-cardiolipin IgM were measured
      repeatedly after admission. Furthermore, platelet count, platelet aggregability
      and plasma platelet factor 4 were also measured. Eleven among the 32 patients
      (34.4%) showed positive in the examination for aPLs. Although aPLs could not
      predict symptomatic vasospasm, once symptomatic vasospasm occurred, patients with
      aPLs frequently demonstrated cerebral infarction and therefore their outcome was
      worse. aPLs were associated with a severe initial clinical grade and SAH grade on
      CT scan. Therefore it may explain the association of aPLs with worse outcome.
      aPLs were detected between 1 and 7 days. Four of 6 patients (67%) with aPLs
      became negative between 7 and 13 days after subarachnoid haemorrhage. The
      mechanism of transient aPLs is unclear but it is more likely to occur in the
      severer grade patients. The reduction in platelet count, the increased platelet
      aggregability, and the increased plasma platelet factor 4 concentration were also
      observed in aPLs-positive patients with symptomatic vasospasm.

PMID- 8748814
TI  - Unusual course of an epidural rhabdomyosarcoma of the upper thoracic spine.
AB  - This report deals with a case of rhabdomyosarcoma in the upper thoracic spine. It
      is of particular interest, not only for the rarity of type and location of this
      tumour, but for its clinical course, which presented fluctuations of neurological
      status, included an acute demonstration of complete paraplegia followed by full
      recovery after conservative treatment, and gradual relapsing of neurological
      deficit, one year later.

PMID- 8748815
TI  - A flexible aneurysm clip applier. Technical note.
AB  - A flexible aneurysm clip applier with a small spindle-shaped head was
      manufactured. It is useful for aneurysmal clipping through a narrow space and the
      clip can be set in various directions due to its flexibility.

PMID- 8748816
TI  - Extended subgaleal fascia--pericranial temporalis flap for skull base
      reconstruction.
AB  - An extended subgaleal fascia pericranial flap based on the temporalis muscle is
      described. The flap receives its vascular nourishment from the arteries supplying
      the temporalis muscle and from the superficial temporal artery. The long length
      of the flap and the ease of its rotation was used effectively to close anterior
      skull basal defects.

PMID- 8748817
TI  - Intracavitary treatment of intrasellar cystic craniopharyngeomas with 90-Yttrium
      by trans-sphenoidal approach--a technical note.
AB  - Intracavitary irradiation of intrasellar cystic craniopharyngeomas by
      stereotactic cyst puncture and injection of radioactive solutions is not yet
      possible. Therefore we designed a new method which allows such intracavitary
      irradiation. Its principle is a transphenoidal approach with only a small bony
      opening of the sella floor, followed by cyst puncture, exclusion of cyst leakage
      by Metrizamid injection under x-ray control, injection of Y-90-colloid solution
      at a dosage which delivers a radiation of 200 Gy to the cyst wall, and finally
      tight closure of the puncture site using fibrin glue and gelfoam. This method has
      been used in three patients with good results (follow-up 12-15 months) and
      without complications. Even though long-term follow-up is not yet available, our
      preliminary results suggest that this method will be useful for future patients
      with intrasellar cystic craniopharyngeomas.

PMID- 8748818
TI  - Transfalcine approach to a contralateral hemispheric tumour.
AB  - In this report an interhemispheric transfalcine approach for contralateral
      hemispheric tumours is described. This surgical approach was successfully
      employed for 4 tumours situated in the parafalcine region. The approach provided
      direct access to the tumour avoiding the need to retract oedematous brain on the
      tumour affected side. The possible indications and advantages of such an
      operation are discussed.

PMID- 8748819
TI  - Risk of infection after cerebrospinal fluid shunt: an analysis of 884 first-time
      shunts.
AB  - Postoperative infections are major complications of cerebrospinal fluid (CSF)
      shunting in the treatment of hydrocephalus and other conditions with obstructed
      CSF circulation. In a retrospective study 884 first-time shunted patients with
      hydrocephalus operated on in the years 1958-1989 were investigated with special
      reference to the infection rate and to the influence of the following variables:
      time period, age of the patient, education of the neurosurgeon, length and time
      of the operation and the exact placement of the distal drain. The overall
      infection rate for all implanted CSF shunts was 7.4% (5.7-9.3%) and the acute
      rate of infection was 6.2% (4.6-7.9%). The rate of infection was virtually
      constant for all variables with the exception of the education of the
      neurosurgeon. Neurosurgical trainees particularly had a significantly higher rate
      of infection. Shunt infection is still a major complication. The infection rate
      has not declined in recent decades. It is not possible to relate any main cause
      to the infection rate. The literature recommends removal of the infected shunt
      combined with antibiotics. The use of prophylactic antibiotics is still
      controversial. No prospective, double-blind studies, including a sufficiently
      large number of patients to evaluate this issue, exist today.

PMID- 8748820
TI  - Anatomy of the parietal lobe: mapping the individual pattern.
AB  - Using magnetic resonance imaging with planes of section tangential to the left or
      right perietal convexity, we studied the sulcus pattern of the parietal lobes in
      50 healthy subjects. The postcentral sulcus and the intraparietal sulcus were
      easily identified. As a characteristic landmark, and corresponding to postmortem
      findings, both sulci joined in 77% of the 100 hemispheres. The presurgical
      recognition of individual parietal lobe anatomy may improve surgical planning, in
      particular with an intended persulcal approach.

PMID- 8748821
TI  - Modification of costotransversectomy to approach ventrally located intraspinal
      lesions. Preliminary report.
AB  - To minimize tissue trauma and to reduce pulmonary complications a modification of
      costotransversectomy is presented. This procedure has been carried out in 6
      patients with ventrally located space occupying lesions in the spinal canal. The
      results are good, complications did not occur. We consider this technique to be
      less traumatic than conventional costotransversectomy while giving the same
      results. Whether the complication rate is lower has yet to be proved in a larger
      series.

PMID- 8748822
TI  - PMN granulocyte elastase--an early indicator of postoperative spondylodiscitis?
AB  - The diagnosis of spondylodiscitis after lumbar disc surgery has been based so far
      on clinical abnormalities, non-specific changes in chemical laboratory parameters
      [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)] and radiological
      examinations such as MRI. Such techniques do not enable any clear diagnosis to be
      made before the 3rd postoperative week. The PMN elastase released from stimulated
      polymorphonuclear granulocytes has been proved to be a good laboratory parameter
      by which it is possible to prognosticate bacterial and abacterial organ
      complications in surgical patients with a high degree of probability. Under
      investigation were 12 patients with spondylodiscitis out of 1162 operations on
      herniated lumbar discs. PMN elastase was determined on the 7th postoperative day.
      In patients with spondylodiscitis and a mean value of 110.5 micrograms/l, the
      elastase was on average higher by a factor of 2.6 as compared to 88 randomly
      selected control patients. Since spondylodiscitis is a rare complication, this
      results in a positive value of only 7%, which does not allow a reliable diagnosis
      of spondylodiscitis by the elastase assay. But because the negative predictive
      value is 100%, it is possible to exclude a postoperative spondylodiscitis already
      on the 7th postoperative day, if the elastase value is normal.

PMID- 8748823
TI  - Pineal region tumours treated with interstitial brachytherapy with low activity
      sources (192-iridium).
AB  - Three patients with tumours of the pineal region underwent interstitial Ir-192
      brachytherapy. Histological diagnoses were obtained in all patients, by
      stereotactic biopsy and included one germinoma, one mixed
      pineoblastoma/pineocytoma, and one astrocytoma grade III. Our approach to pineal
      region neoplasms is first to decide whether stereotactic biopsy or surgery should
      be performed. When a pineal lesion is thought to be benign on the basis of
      imaging, such as benign teratoma, surgery is performed to resect the entire
      lesion. When a definitive diagnosis is not possible, stereotactic biopsy is
      performed to obtain a histological diagnosis for treatment planning, using a
      Brown-Roberts-Wells (BRW) stereotactic apparatus with computed tomography (CT) or
      magnetic resonance imaging (MRI). When a lesion is malignant and localized,
      stereotactic implantation of catheters for interstitial brachytherapy is
      performed simultaneously. Radioactive Ir-192 seeds are inserted into the
      catheters and maintained for 5-10 days to give 36 Gy of irradiation at the tumour
      periphery. Sequential CT scans and MRI after treatment revealed tumour
      disappearance in two patients with germinoma and high grade astrocytoma and
      tumour reduction in the patient with mixed pineoblastoma/pineocytoma. No
      significant morbidity or mortality occurred in any of these patients after
      stereotactic biopsy and brachytherapy. The technique and the advantages of this
      therapeutic approach to selected pineal region tumours are described and
      discussed.

PMID- 8748824
TI  - Cavernous malformations of the optic chiasma.
AB  - Two cases of cavernous malformation of the optic chiasm are reported, and 12
      previously reported cases are reviewed. The first patient presented with
      gradually progressive and the second patient with a subacute chiasmal syndrome.
      Total excision was performed in both cases. Visual function improved slightly
      after surgery in the first patient while the other showed marked improvement.
      Although cavernous malformations are angiographically occult, pre-operative
      diagnosis has become possible based on the characteristic features such as
      repeated haemorrhages in multiple sinusoidal structures as revealed by magnetic
      resonance imaging (MRI). A gliotic interspace between the malformation and normal
      neural tissue provides a plane of cleavage for dissection which permits total
      excision without causing new deficits. Review of previously reported cases
      revealed that chiasmal cavernous malformations haemorrhage more frequently than
      those in the brain. Early diagnosis with total excision is the treatment of
      choice for cavernous malformations of the optic chiasma.

PMID- 8748825
TI  - Analysis of the growth rate and cavernous sinus invasion of pituitary adenomas.
AB  - Pituitary adenomas generally are regarded as benign tumours, but a part of them
      can invade the cavernous sinus and recur. We examined 43 pituitary adenomas for
      the following factors: tumour volume, endocrinological function, cavernous sinus
      invasion, and growth rates examined by using anti-proliferating cell nuclear
      antigen (PCNA) and MIB1 (a novel anti-Ki-67) as markers. There was significant
      correlation between PCNA- and MIB1-positive cell rates and PCNA- and MIB1
      positive cell rates were higher in the three cases with rapid regrowth than in
      the other cases. Staining was stronger and more distinct for MIB1 than for anti
      PCNA; thus, MIB1-positive cells were easily distinguished by their intense
      immunoreactivity. MIB1 may be useful for detecting those rare cases with rapid
      regrowth even when initially regarded as benign tumours. Adenomas with cavernous
      sinus invasion were significantly larger than those demonstrating no invasion.
      However, no significant difference was found in the frequency of PCNA- or MIB1
      positive cells between adenomas with and without cavernous sinus invasion. These
      findings suggest that cavernous sinus invasion and growth rate are independent
      biological factors. Therefore, cavernous sinus invasion may be due to chemical
      factors produced by the tumour itself rather than as a result of rapid tumour
      growth.

PMID- 8748826
TI  - Tenascin distribution in human brain tumours.
AB  - Using a monoclonal antibody specific for human tenascin (TN), 180 intracranial
      growths were immunohistochemically studied. In 69 cases of meningioma, neoplastic
      cells were negative, with some positivity being observed only in the perivascular
      and the supporting stroma, especially in anaplastic meningiomas. In 57 cases of
      glioma different degrees of reactivity occurred in both the cellular
      conglomerates and the stromal components of the tumours. A higher variability in
      reactivity was observed in anaplastic astrocytomas and glioblastomas. The most
      constant finding of the study was the staining of the stroma, which was observed
      in all types of growths, including metastasis, abscess and tuberculoma. The
      results are consistent with the hypothesis that tenascin is a stromal marker
      rather than a true marker of malignant tumours. The heterogeneous distribution of
      TN in anaplastic gliomas may be a factor in the variable response to treatment
      with radiolabelled anti-TN monoclonal antibodies.

PMID- 8748827
TI  - Effect of ultra-early referral on management outcome in subarachnoid haemorrhage.
AB  - A study was conducted to clarify whether ultra-early referral of patients with
      subarachnoid haemorrhage (SAH) is effective for improving the management outcome.
      The subjects were 455 patients who were admitted within 6 h after initial SAH. Of
      these patients, 289 were treated surgically, 159 of them within 24 h. At 6
      months, 228 patients (50%) had a favourable outcome including good recovery or
      moderate disability, 37 (8%) had severe disability, and 190 (42%) had an
      unfavourable outcome including vegetative state or death. Of 214 patients with an
      admission grade IV or V, 47 (22%) had a favourable outcome. In 10 patients,
      emergency procedures such as haematoma removal or ventriculostomy were definitely
      effective, and in 13, early surgery may have been the reason for the improved
      outcome. However, in 24 patients, the reasons for a favourable outcome were not
      related directly to ultra-early referral; in 19 of them, there was spontaneous
      improvement of clinical grade and/or no SAH on computed tomography. Of 218
      patients with admission grade I or II, 30 (14%) had an unfavourable outcome, and
      in 12 of them, this was ascribed to rebleeding. The rebleeding rate and severity
      of vasospasm were not significantly reduced by surgery carried out within 24 h
      after SAH, in comparison with surgery carried out between 24 and 48 h, and there
      was no significant difference in surgical outcome between them. It is concluded
      that although ultra-early referral of patients with SAH was expected to improve
      the outcome in emergency cases, no substantial improvement in overall management
      outcome seems to have been achieved by this policy.

PMID- 8748828
TI  - Coating of intracranial aneurysms: a long-term follow-up study of 34 cases.
AB  - We performed a retrospective follow-up study of 33 patients, with 34 ruptured
      aneurysms, treated by coating using bio-adhesive polymers. The rebleeding rate
      after a mean follow-up of 10 years was 18% (6 patients), with 4 cases of early
      haemorrhage and 2 late rebleedings (late rebleeding rate of 0.7% per year). All
      rebleedings proved fatal. Coating of the aneurysmal wall provides some protection
      in patients with "unclippable" aneurysms, but is obviously inferior to clipping,
      and should be used only in very selected cases.

PMID- 8748829
TI  - Amount of subarachnoid blood and vasospasm: current aspects. A transcranial
      Doppler study.
AB  - Subsequent to admission after aneurysmal subarachnoid haemorrhage (SAH), 120
      patients (74 women and 46 men) underwent microsurgical clipping of a total of 158
      cerebral aneurysms within 96 hours after the bleed. Their mean age was 46 (20-91)
      years. Computed tomography (CT) findings were graded according to the modified
      Fisher scale and all patients had daily transcranial doppler (TCD) recordings of
      their basal cerebral arteries. In 19% of SAH was grade I on CT, in 44% grade II
      and in 37% grade III. The rate of patients who developed severe vasospasm as
      documented by TCD (mean blood flow velocities exceeding 160 cm/s on 2 or more
      consecutive days) was 39% for grade I patients, 26% for grade II patients and 34%
      for patients with SAH grade III on the initial CT. There was no difference in the
      rate of occurrence of severe vasospasm, when the patients were split into 2
      groups according to the time of performance of the initial CT scan-within 24
      hours, and 48-80 hours after SAH, respectively. It is concluded that the amount
      of subarachnoid blood on the initial CT scan should no longer be used as the
      indicator for occurrence and severity of the multifactorial entity vasospasm.

PMID- 8748830
TI  - Percutaneous balloon compression of the Gasserian ganglion in trigeminal
      neuralgia. Long-term results in 150 cases.
AB  - One hundred and fifty patients with trigeminal neuralgia were treated by
      percutaneous compression of the Gasserian ganglion (PCGG) during the last 8
      years. The technique is the one described by Mullan with the balloon inflated
      during 6 minutes with 0,7 cc of contrast medium. Over a follow-up period ranging
      from 6 months to 8 years with an average of 4 years, one hundred and four
      patients (69,3%) have remained painfree. Postoperative complications included
      dysaesthesias in 16 patients (moderate in 15), hypo-aesthesia in 140 (moderate in
      138), hypo-acousia and otalgia in ten, and masticatory weakness also in ten. The
      recurrence rate was 30%. The main advantages of the procedure are exceptionally
      severe dysaesthesias (one case), the rarity of corneal complications (4 cases),
      the short hospital stay (three days on average). Its disadvantage is the need for
      a general anaesthetic. This study shows that percutaneous compression is
      efficacious and technically easy.

PMID- 8748831
TI  - Stimulation of the ventral intermediate thalamic nucleus in tremor dominated
      Parkinson's disease and essential tremor.
AB  - Based on Benabid's experimental and clinical findings that low-frequency (50 Hz)
      electrical stimulation of the ventral intermediate thalamic nucleus may increase
      tremor, while higher frequencies (> 100 Hz) lead to suppression of the tremor, we
      implanted a stimulation electrode in 33 thalami among 27 patients. Six patients
      were implanted bilaterally. 23 suffered from Parkinson's disease, 4 from
      essential tremor. All patients had a drug-resistant tremor. The Vim target was
      calculated based on stereotactic ventriculography. An intra-operative
      neurophysiological target control was performed on all patients. After a
      monopolar (12 thalami) or quadripolar (21 thalami) lead was implanted we then
      connected it to a percutaneous extension lead. In the days following the surgery
      a test stimulation was performed. In all but one patient stimulation resulted in
      a suppression of the tremor. In a second procedure, a pulse generator (ITREL II;
      MEDTRONIC) was implanted and connected subcutaneously to the thalamic lead. After
      implantation of the pulse generator all patients stimulate chronically while some
      turn off the stimulator at night. In 21 thalami total suppression of tremor was
      observed, 6 showed major improvement, 4 only minor improvement. There was no
      significant effect on any other existing symptom of Parkinson's disease. Due to
      the proximity of Vim to the sensory thalamus the majority of the patients (27
      thalami) report slight temporary paraesthesias when the pulse generator is turned
      on. Two report permanent paraesthesias when stimulation is on. In 4 cases a
      slight dysarthria occurs under stimulation. In 2 the dysarthria is marked. In one
      case dysequilibrium occurs under stimulation. All these side effects are
      reversible when stimulation is turned off. In 3 patients, the lead was displaced
      due to an insufficient lead fixation, thus making a second procedure necessary to
      correct the electrode position. We had one complication due to bleeding at the
      burr hole side. Follow-up ranges from 3 to 48 months. So far in no cases has the
      effect of stimulation worn off. In conclusion we regard Vim neurostimulation as
      an effective and safe alternative to conventional thalamotomy and recommend that
      it should be considered in cases in which drug therapy has failed to affect
      Parkinsonian or essential tremor. Moreover, we believe that this procedure is a
      less invasive and equally efficient alternative to classic thalamotomy and thus
      should be given preference.

PMID- 8748832
TI  - Early blood-brain barrier disruption after high-dose single-fraction irradiation
      in rats.
AB  - We studied the effect of high-dose single-fraction irradiation on the
      permeability of the blood-brain barrier (BBB) in rat brains. Immunohistochemistry
      with an antibody to serum albumin was used as a sensitive method for detecting
      the extravasation of endogenous serum components. Extravasation of albumin was
      detected as early as 1 day after irradiation with 20 or 40 Gy. Immunoreactivity
      reached its maximum after 3 days, gradually decreased during the following few
      weeks and had disappeared by day 30. Extravasation was much greater after
      irradiation with 80 Gy and continued to increase during the whole period of the
      experiment (6 days). Disruption of BBB this early after irradiation has not been
      previously documented. The time course of observed serum albumin extravasation,
      however, agrees well with the previous ultrastructural evidence for increased BBB
      permeability after irradiation with 27 Gy in monkey brains. This transient
      impairment of BBB may contribute to the reversible neurological symptoms after
      radiosurgery. It may also allow drugs that normally not pass the BBB to do so and
      thus disperse in the brain when administered at this time.

PMID- 8748833
TI  - Subarachnoid haemorrhage induced proliferation of leptomeningeal cells and
      deposition of extracellular matrices in the arachnoid granulations and
      subarachnoid space. Immunhistochemical study.
AB  - Subarachnoid haemorrhage (SAH) often leads to subarachnoid fibrosis and resultant
      normal pressure hydrocephalus; however, how subarachnoid fibrosis occurs is
      unknown. We examined the changes within arachnoid granulations (AGs) and the
      subarachnoid space (SAS) chronologically at the parasagittal region obtained from
      patients with SAH at autopsy and made comparison with controls by immunostaining
      for cytokeratin, specific marker for leptomeningeal cells and by the elastica
      Masson-Goldner methods. Within a week some AGs were torn, and many inflammatory
      cells filled the AGs and SAS. Cytokeratin positive cells were scarce. During the
      next two weeks cytokeratin positive cells increased. After three weeks, AGs and
      SAS were filled by dense deposits of extracellular matrices surrounded by
      multiple layers of leptomeningeal cells.

PMID- 8748834
TI  - Percutaneous jugular placement of ventriculo-atrial shunts using a split sheath.
      Technical note.
AB  - The percutaneous placement of ventriculo-atrial (V-A) shunts for treatment of
      hydrocephalus has been previously reported by several authors as a simplified
      procedure. However, this technique did not avoid the use of a distal connector
      between the outlet catheter and the atrial one, which may lead to a
      disconnection. A technique of percutaneous V-A shunt insertion using a split
      sheath is described and illustrated with a series of 22 patients. The use of a
      split sheath eliminates any distal connector thus avoiding the risk of shunt
      disconnection and reducing the operating time. The average operating time was 31
      min. This rapid procedure allowed us to operate on two of our patients under
      local anaesthesia. The correct placement of the atrial catheter tip was performed
      under fluoroscopic control and always confirmed by postoperative radiographs. Two
      incidents of carotid artery puncture were controlled by simple local compression
      without further consequences. The mean follow-up time is one year. All the
      patients' clinical conditions improved. We are encouraged to use this V-A
      technique more frequently as a method of choice in the treatment of adult
      hydrocephalus or when the peritoneal cavity is inaccessible in children. The use
      of a split sheath is successful in reducing the operating time and avoiding the
      use of a distal connector.

PMID- 8748835
TI  - Microclip haemostasis for surgical treatment of cerebral arteriovenous
      malformations. Technical note.
AB  - The authors describe newly designed microclips and their utility in obtaining
      haemostasis during the surgical resection of cerebral arteriovenous
      malformations. The microclips are particularly well-suited for controlling
      bleeding from small fragile vessels often encountered on the periphery of large
      arteriovenous malformations during the final stages of a surgical procedure.
      Histological examination of these vessels revealed very thin dilated walls
      without elastic layers, causing easy rupture. Hence, haemostasis using
      conventional means, such as bipolar coagulators, can be extremely difficult. We
      have used microclips on such vessels in 14 patients with arteriovenous
      malformations and controlled bleeding successfully.

PMID- 8748836
TI  - Infratemporal fossa interdural approach for trigeminal neurinomas.
AB  - A small craniectomy in the infratemporal fossa incorporating the foramen ovale
      was used to resect 4 large trigeminal neurinomas. The tumour extended from the
      posterior cranial fossa and involved Meckel's cave and the lateral wall of the
      cavernous sinus in each instance. The dural sheath around the mandibular nerve
      and Gasserian ganglion was opened to expose the entire lesion. The head position
      and the surgeon's view of the tumour were modified to obtained a basal view. The
      craniectomy at this strategic site provided an avenue for control of the carotid
      artery at the petrous apex, avoided the need for brain retraction and permitted
      safe and complete resection of the tumours. The approach appears to be ideal for
      selected cases of trigeminal neurinomas.

PMID- 8748837
TI  - An intra-arterial electrode for intracranial electro-encephalogram recordings.
AB  - A new method for intracranial monitoring of brain electrical activity by means of
      an intra-arterial guide wire as electrode is described. We carried out
      intracranial electro-encephalography (EEG) using an insulated Seeker Lite-10
      guide wire 18 times in 14 patients: ten times in 6 patients with cerebral
      arteriovenous malformation (AVM) before embolization, and another 8 times in 8
      patients with epilepsy. In all cases, a 2-5 times stronger high voltage potential
      EEG compared with scalp EEG could be recorded. In 3 patients with complex partial
      epilepsy, intra-arterial (IA) EEG was recorded under subdural strip electrode
      monitoring, and IAEEG at the sphenoidal portion of the middle cerebral artery was
      compared with subdural electrode recordings. Frequent interictal spike discharges
      recorded with subdural electrodes in the lesional medial temporal lobe were
      simultaneously visible on IAEEG recording. This method is equivalent to that
      using a semi-invasive electrode, but ECoG recording can be performed at
      angiography. IAEEG is a method of electrode recording that has the possibility of
      clinical application.

PMID- 8748838
TI  - Atlanto-axial instability of a hypoplastic upper cervical spine. Case report.
AB  - The authors report on the development of myelopathy in a case of hypoplastic
      upper cervical spine with atlanto-axial instability. Its surgical treatment with
      transarticular screw fixation and interlaminar fusion is outlined.

PMID- 8748839
TI  - The transzygomatic approach: a long-term clinical review.
AB  - The transzygomatic approach has been utilised to improve access to the skull
      base, infratemporal fossa and orbit for a number of years. It provides a low
      anterolateral approach to the skull base, along the floor of the middle fossa. It
      allows both a transsylvian and subtemporal approach with a reduction in brain
      retraction and better exposure of adjacent neurovasculature structures. A long
      term review of 53 patients is presented highlighting outcome at two years post
      surgery and morbidity of the approach. It is concluded that the technique is
      versatile and can be used to improve exposure of a variety of anatomical
      locations. There is minimal long term morbidity attributable to the surgery of
      access and the majority of patients have had good outcomes.

PMID- 8748840
TI  - Secondary manifestation of medulloblastoma: metastases and local recurrences in
      66 patients.
AB  - Although primary treatment of medulloblastoma is now successful in a high
      percentage of patients, its secondary manifestations still bear a poor prognosis.
      Thorough studies of secondary manifestations are therefore pivotal to plan
      therapeutic approaches for the long-term management of medulloblastoma. Here we
      describe the incidence of secondary tumour manifestations in 66 patients of a
      single centre who underwent surgery for medulloblastoma between 1975 and 1990. No
      patient was excluded due to a poor postoperative course. Thirty-five patients
      showed evidence of secondary tumour growth. Of these, 17 suffered from local
      recurrence, and 27 developed metastastatic disease. The median latencies for
      secondary manifestations were 25 months for local recurrence (n = 17), 11 months
      for spinal metastases (n = 10), 15 months for supratentorial metastases (n = 8),
      8 months for subleptomeningeal dissemination (n = 6), and 23 months for systemic
      metastases (n = 8). Two patients developed primary metastatic spread to the
      posterior fossa. Of 8 patients with supratentorial metastases, 6 developed fronto
      basal lesions. In our patients, 89% of secondary lesions occurred within less
      than 3 years after primary diagnosis. 85% of patients with extra-axial tumour
      spread had been treated with a permanent shunt. Radical tumour resection and
      radiotherapy with 30 Gy to the neuraxis and 20 Gy boost to the posterior fossa
      was an important prognostic factor in this series. Patients with additional
      chemotherapy did not benefit significantly from this treatment. We conclude that
      optimal management of the primary lesions should aim at (i) total resection, (ii)
      avoid permanent shunting, and (iii) completion of the radiotherapy with inclusion
      of the medial frontobasal cisterns in the radiotherapeutic regimen. Our analysis
      suggests that adequate postoperative screening programmes should consist of 3
      monthly scans of the neuraxis in the first three postoperative years and 6
      monthly scans thereafter.

PMID- 8748841
TI  - Invasive meningioma: a tumour with high proliferating and "recurrence" potential.
AB  - A study was undertaken to investigate the correlation between histological
      invasiveness and proliferating potential and clinical recurrence in meningioma.
      In 39 meningiomas, the histological findings at the tumour-brain interface zone
      were classified into 3 types, consisting of 29 cases of non-invasion (NON). 7
      cases of nodular invasion (NOD), and 3 cases of intermingled invasion (INT).
      Proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizer
      region (AgNOR) indices were studied. PCNA indices (mean +/- standard error) of
      NON, NOD. and INT were 1.7 +/- 0.1%, 5.2 +/- 0.5%, and 7.5 +/- 0.7%.
      respectively, and the AgNOR indices (dot number/nucleus) were 1.50 +/- 0.03, 2.00
      +/- 0.04, and 2.22 +/- 0.07, respectively. Significant differences were found
      among the three types in both parameters. Clinically, tumour recurrence was
      observed in 1/29 NON, 4/7 NOD, and 2/2 INT cases, indicating a higher incidence
      of recurrence in invasive meningiomas (NOD plus INT). Four of 32 patients who
      underwent gross total removal of the tumours showed recurrence, and all of these
      four tumours were invasive meningiomas. The results of the present study showed
      that tumour invasiveness as measured by PCNA + AgNOR indices correlated well with
      high proliferative potential and clinical recurrence.

PMID- 8748842
TI  - Development of intracranial meningiomas at the site of cranial fractures. Remarks
      on 15 cases.
AB  - The authors present a retrospective study of 15 patients with post-traumatic
      intracranial meningioma. The 15 cases were selected according to the criteria
      specified in the relevant literature. Assessment of clinical characteristics in
      these patients seems to confirm that in some cases head trauma may be a factor
      contributing to the development of meningioma.

PMID- 8748843
TI  - Detection of cerebrospinal fluid leakage by isoelectric focusing on
      polyacrylamide gels with silver staining using the PhastSystem.
AB  - Cerebrospinal fluid (CSF) leakage, which sometimes occurs after skull trauma, is
      a life-threatening condition. A prompt start with antibiotics and/or prompt
      surgical treatment of fistulas is essential to avoid severe complications. This
      requires a fast and reliable method for detecting CSF leakage. This paper
      describes a fast (< 2 h) method based on the identification of the tau protein
      (beta 2-transferrin) band(s). Tau protein is a brain-specific variant of
      transferrin that is characteristic of CSF. The method includes iso-electric
      focusing (IEF) on pre-cast polyacrylamide gels and silver staining using the
      PhastSystem, an automated instrument for electrophoresis and staining. In the
      present study, this technology was applied on 200 consecutive CSF samples, 32 of
      which were from healthy volunteers. Tau protein was detected in all CSF samples
      but 5 (2.5%), all of which were from patients with blood-brain barrier (BBB)
      damage. In these cases, the tau protein band was indistinct when direct silver
      staining was used. Therefore, immunofixation with an antitransferrin antibody was
      performed, and after that the tau protein band was easy to detect. The
      specificity of the method was high, since no brain-specific tau protein band was
      detected in serum, tears, saliva, or nasal secretion. As IEF of CSF using the
      PhastSystem is increasingly used as the routine method for detection of
      oligoclonal bands of IgG in neurological disorders, it could readily be used in
      the clinical (neuro) chemical laboratory also for the less frequent cases of
      suspected CSF leakage.

PMID- 8748844
TI  - The surgical anatomy of thoracic facet denervation.
AB  - Thoracic percutaneous facet denervation has been employed for the treatment of
      thoracic zygapophysial joint pain. But the surgical anatomy of this procedure has
      been assumed to be the same as for lumbar medial branch neurotomy. To establish
      the anatomical basis for thoracic medial branch neurotomy, an anatomical study
      was undertaken. Using an X40 dissecting microscope, a total of 84 medial branches
      from 7 sides of 4 embalmed human adult cadavers were studied. The medial branches
      of the thoracic dorsal rami were found to assume a reasonably constant course.
      Upon leaving the intertransverse space, they typically crossed the superolateral
      corners of the transverse processes and then passed medially and inferiorly
      across the posterior surfaces of the transverse processes before ramifying into
      the multifidus muscles. Exceptions to this pattern occurred at mid-thoracic
      levels (T5-T8). Although the curved course remained essentially the same, the
      inflection occurred at a point superior to the superolateral corner of the
      transverse process. At no time during the dissection were nerves encountered
      crossing the junctions between the superior articular processes and transverse
      processes which have been the target points advocated for thoracic facet
      denervation. Rather, the results of this study indicate that the superolateral
      corners of the transverse processes are more accurate target points.

PMID- 8748845
TI  - The C-reactive protein for detection of early infections after lumbar
      microdiscectomy.
AB  - The tendency for short hospitalization after lumbar microdiscectomy implies the
      need for early confirmation or disapproval of serious postoperative infections
      such as spondylodiscitis or deep wound infections. The C-reactive protein (CRP)
      is a well-known screening parameter for monitoring postoperative infectious
      complications in other fields. Our objective was to establish the diagnostic
      significance of CRP-in comparison with ESR and WBC-for monitoring infectious
      complications after lumbar microdiscectomy. Over a 15 months period we studied
      prospectively a homogeneous group of N = 400 patients with lumbar disc
      herniations who were operated on a single level for the first time. CRP, ESR and
      WBC values were determined in all patients pre-operatively, and on postoperative
      days 1 and 5. Clinical and laboratory findings were correlated and the diagnostic
      significance of CRP, ESR and WBC calculated. N = 385 (96%) patients had an
      uneventful postoperative course. N = 15 (4%) patients developed infectious
      complications, of which N = 6 (1.5%) were unrelated and N = 9 (2.5%) related to
      surgery. Evaluation of the laboratory values showed: The CRP baseline is a very
      individual value of no prognostic relevance. A high postaggression peak is
      typical and essential as a reference value for only the future time course will
      disclose any infection. We found 0% false negative and 4% false positive results
      on day 5. The sensitivity for serial CRP testing was calculated as 100% and
      specificity as 95.8%. ESR (sensitivity: 78.1%/specificity: 38.1%) and WBC
      (sensitivity: 21.4%/specificity: 76.8%) both failed to reach such distinct
      diagnostic significance on day 5. The C-reactive protein has thus proved to be a
      reliable, simple and economical screening test for infectious complications after
      lumbar microdiscectomy, superior to classical laboratory parameters.

PMID- 8748847
TI  - Bifid median nerve: report of two cases.
AB  - The median nerve divides into its terminal branches at or proximal to the distal
      edge of the flexor retinaculum. An anatomy of the median nerve within the carpal
      tunnel is reported in two separate cases. Emphasis has been given to the value of
      direct vision when incising the flexor retinaculum in order to avoid injure of
      the median nerve.

PMID- 8748846
TI  - Repair of the facial nerve in the cerebellopontine angle using freeze-thawed
      skeletal muscle autografts. An experimental surgical study in the sheep.
AB  - Six adult blackface sheep underwent repair of the transected facial nerve in the
      cerebellopontine angle using short freeze-thawed muscle autografts. A typical
      facial palsy was observed on the side of the intervention immediately after
      operation. The sheep were allowed to recover for one year by which time clinical
      observation showed a complete recovery of the facial palsy in 5 sheep and a
      partial recovery in the remaining sheep. Under general anaesthesia function of
      the repaired VIIth nerve and the normal contralateral facial nerve were assessed
      using electrophysiological stimulating and recording techniques. These studies
      showed restoration of facial nerve continuity to have taken place with functional
      reinnervation of target facial muscles. Electrophysiological indices of nerve
      function were consistent with those expected after repair of any peripheral
      nerve. Morphometric study of the nerves after their removal showed structural
      changes which though quantitatively different from those of normal nerve were
      consistent with those seen in other sites and studies where nerves have been
      repaired. This technique is discussed as a possible treatment for facial nerves
      whose continuity is disrupted during the removal of cerebellopontine angle
      tumours.

PMID- 8748848
TI  - Acute subdural haematoma from ruptured intracranial aneurysms.
AB  - Acute subdural haematoma (SDH) secondary to a ruptured intracranial aneurysm is a
      rare event. Out of a total of 292 patients with a verified aneurysm (period 1986
      1992) in five cases SDH was the diagnosis on CT-evaluation. One patient was in
      such a bad condition that no treatment was indicated. The remaining four patients
      were operated on: craniotomy and haematoma evacuation in two cases, craniotomy
      for haematoma evacuation and aneurysm clipping in the other two cases. Two
      patients died and two achieved a good outcome.

PMID- 8748849
TI  - Timing of operation for ruptured cerebral aneurysm and long-term recovery of
      cognitive functions.
AB  - Advantage and disadvantages of early and late operation for ruptured cerebral
      aneurysm are controversially evaluated with regard to peri-operative operation
      outcome and long-term cognitive recovery. In this retrospective analysis 22
      patients with early surgery (ES) within three days after subarachnoid haemorrhage
      (SAH) and 22 patients with late surgery (LS) at least 14 days after SAH were
      studied. Patients were pair-wise matched by degree of SAH localisation of
      aneurysm and age at SAH. On average three years after SAH both groups were
      examined individually with a comprehensive neuropsychological test battery
      including tests of premorbid intelligence, concept formation, memory, visuomotor
      speed, aphasia screening, and mood. ES and LS patients were well comparable in
      terms of years of education and level of premorbid intelligence. There was a
      clear influence of patients age on fluid intelligence tests, indicating a general
      change-sensitivity of tests. No influence of degree of SAH and localisation of
      aneurysm could be detected. There were also no differences between ES and LS
      patients in neuropsychological tests sensitive to brain damage, suggesting that
      the decision for early or late surgery for ruptured cerebral aneurysm can be
      based upon surgical reasons at the time of the SAH.

PMID- 8748851
TI  - Vasospasm diagnosis: theoretical and real transcranial Doppler sensitivity.
AB  - In 40 patients middle cerebral artery trunk (M1) flow velocity was recorded just
      before 54 carotid angiography in 54 cases exhibiting vasospasm after aneurysm
      rupture. Angiographic vasospasm distribution was studied; cases of symptomatic
      vasospasm were noted and were compared with transcranial Doppler data.
      Angiographic vasospasm was present in M1 in 41/54 carotid angiograms. Postulating
      that all the cases of M1 angiographic vasospasm should be identified by
      transcranial Doppler, the theoretical sensitivity of TCD was 76%. In this series
      however the real sensitivity of TCD in vasospasm diagnosis was only 70%: besides
      13 cases where vasospasm was not present in M1 (mainly after ACoA Aneurysm
      rupture), TCD failed to identify 3 cases of M1 angiographic vasospasm. Vasospasm
      may not be located in M1 even when severe and symptomatic (4 cases in this
      series). Transcranial Doppler remains a mediocre tool for identifying vasospasm
      after anterior communicating artery aneurysm rupture (sensitivity: 55%). Its
      reliability is better after internal carotid aneurysm rupture (sensitivity: 72%)
      and excellent after middle cerebral artery aneurysm rupture (sensitivity: 93%).
      In order to test the drugs or methods used to prevent or combat vasospasm,
      angiography has to be considered when during the vasospasm risk period TCD does
      not demonstrate vasospasm in M1, either in patients in whom clinical
      deterioration is occurring without other obvious explanation, or in all patients.

PMID- 8748850
TI  - Effects of intravenous nitroglycerin combined with dopamine on intracranial
      pressure and cerebral arteriovenous oxygen difference in patients with acute
      subarachnoid haemorrhage.
AB  - The effects of intravenous nitroglycerin (NTG) combined with dopamine on
      intracranial pressure (ICP) and cerebral arteriovenous oxygen difference (AVDO2)
      were studied in 11 patients with acute subarachnoid haemorrhage (SAH). The study
      was performed on Days 1 to 3 of SAH after aneurysmal clipping. Treatment
      consisted of an intravenous drip infusion of NTG in increasing incremental doses
      of 0.5, 1.0, 1.5, 2.0, and 2.5 micrograms/kg/min at one-hour intervals. Dopamine
      (5 to 10 micrograms/kg/min) was also given concurrently to maintain systemic
      blood pressure. ICP values before NTG administration ranged from 7 to 24 mmHg
      (mean. 11.91 +/- 5.30 mmHg). ICP began to increase immediately after the
      administration of NTG 0.5 microgram/kg/min and peaked at 14.64 +/- 5.93 mmHg 10
      minutes after onset of infusion. Thereafter, ICP gradually returned to
      pretreatment levels. Increasing the dose of NTG failed to induce further
      significant rises in ICP. Mean AVDO2 before NTG administration was 4.69 +/- 0.62
      ml/dl. This parameter showed no significant change during NTG infusion, although
      cerebral perfusion pressure decreased to between 75% to 94% of the control value
      after NTG administration. These results indicate that continuous NTG infusion
      combined with dopamine does not have adverse effects on ICP (the ICP increase is
      minimal and transient) and may even have beneficial effects on CBF in patients
      with acute SAH.

PMID- 8748852
TI  - Effect of dotarizine on CO2-dependent cerebrovascular reactivity.
AB  - Dotarizine is chemically related to calcium antagonist cinnarizine and
      flunarizine. The study presented investigates the influence of the drug on the
      diameter of cortical arteries and cerebral blood velocity measured in the MCA in
      two groups of anaesthetized cats. Changes of vessel diameter were measured
      indirectly using photographs of the cerebral cortex during experiments, and flow
      velocity was measured using transcranial Doppler sonography. Dotarizine was
      administrated by 20 minute intravenous infusion in a dose of 0.05 mg/kg/min. In
      the first group of animals the infusion was started during normoventilation, in
      the next group the infusion started during 30th minute of hyperventilation. The
      most conspicuous data were obtained in experiments conducted in hyperventilated
      animals where dotarizine abolished the vasoconstrictive effect of
      hyperventilation. The results suggest that dotarizine has a pronounced effect on
      basal as well as cortical arteries of the brain.

PMID- 8748853
TI  - Frequency and causes of shunt revisions in different cerebrospinal fluid shunt
      types.
AB  - Shunt complications and revisions are common in hydrocephalic patients treated
      with a ventriculo-atrial or a ventriculo-peritoneal shunt. The reported revision
      rate differs very much but the rate of revision is close to 50% in many papers.
      Data from 884 hydrocephalic patients treated with various shunt types in the
      period 1958-1989 were recorded retrospectively in order to evaluate the frequency
      of revision for various shunt types and secondly to analyse the specific reasons
      for the shunt revisions. The rate of shunt revision was 45%. The Pudenz shunt was
      revised more often (62%) than the remaining shunt types. The Hakim and the Orbis
      Sigma shunts had fewer revisions (35% and 27%, respectively) than the other
      observed shunt types. A defect of or an obstruction in the ventricular catheters
      was a frequent cause of revision followed by a defect or an obstruction of the
      distal catheter, a displacement of the distal catheter and an acute infection.
      Because of the higher rate of revision for the Pudenz shunt the rate of the above
      mentioned specific complications is also higher in most of the subgroups for that
      specific shunt type. Driven by these experiences it is reasonable to seek to
      develop and introduce new shunt types in an attempt to reduce the complication
      rate.

PMID- 8748854
TI  - The relation of intracranial pressure B-waves to different sleep stages in
      patients with suspected normal pressure hydrocephalus.
AB  - The interpretation of data from continuous monitoring of intracranial pressure
      (ICP) in patients with suspected normal pressure hydrocephalus (NPH) is the
      subject of controversy. Despite the fact that overnight ICP monitoring is widely
      used for the diagnosis of NPH, normative criteria are poorly defined. The present
      study demonstrates that there is a relationship between the relative frequency,
      the absolute amplitude, the wavelength and the morphology of B-waves and
      different sleep stages. Intraventricular intracranial pressure was recorded
      continuously overnight in 16 patients with suspected normal pressure
      hydrocephalus. Simultaneous polysomnography was performed to investigate the
      relation of spontaneous ICP oscillations to different sleep stages. A correlative
      analysis was done with the data of 13 patients. Three patients were excluded, one
      who was awake throughout the night and two in whom polysomnography was incomplete
      due to technical reasons. The mean resting cerebrospinal fluid (CSF) pressure was
      12.87 cm CSF. B-waves were observed in the ICP recordings of all patients. They
      were present for a mean of 72% of the total recording time. The relative
      frequency of B-waves was higher during REM sleep and sleep stage 2 as compared to
      wakefulness (87.8% and 83.2% vs. 56. p < 0.05). The absolute amplitude was higher
      during REM sleep than in wakefulness (9.56 vs. 3.44 cm CSF, p < 0.05).
      Wavelengths were longer in REM sleep than in wakefulness and stages 1 and 2 (62.4
      vs. 42, 40.7 and 44.8 sec, p < 0.05). The morphology of B-waves was also related
      to different sleep stages. Ramp-type B-waves were associated with REM sleep in
      six patients, however, were also present in sleep stage 2 in three of them.
      Knowledge of the relation of spontaneous ICP oscillations to different sleep
      stages may help to establish physiological foundations and alterations.
      Furthermore, polysomnography may be useful to avoid erroneous interpretation of
      ICP recordings due to sleep stage related variability.

PMID- 8748855
TI  - The pretemporal approach to the interpeduncular and petroclival regions.
AB  - A pretemporal approach to the interpeduncular and petroclival regions is
      described. Through a frontotemporal craniotomy based very low in the middle fossa
      the temporal lobe is completely exposed. The Sylvian, carotid, chiasmatic, and
      lamina terminalis cisterns are widely opened. The arachnoid fibers between the
      uncus and the frontal lobe, as well as those binding the temporal lobe to the
      tentorial edge and to the oculomotor nerve are also separated. The bridging veins
      from the temporal pole to the spheno-parietal sinus are usually coagulated and
      sacrificed allowing for posterior displacement of the temporal lobe. The approach
      combines the advantages of both the classical pterional and subtemporal
      approaches providing unhindered exposure of the anterior portion of the tentorial
      incisura in dealing with vascular and tumoural lesions arising at the sellar,
      parasellar, and interpeduncular regions, and at the superior aspect of the
      petroclival region.

PMID- 8748856
TI  - Middle fossa sub-Gasserian ganglion approach to clivus chordomas.
AB  - A modified lateral subtemporal, transpetrous apex and sub-Gasserian ganglion
      approach was found to be most suitable for clival chordomas. The approach
      selection was based on the typical anatomical relationship of chordomas in terms
      of site of origin, pattern of growth and neural and vascular displacements. The
      approach was suitable to deal with tumour anterior and lateral to the brain stem,
      the clival part of the tumour and its sub-cavernous sinus extensions. The carotid
      artery was under control. The approach had the advantage of being simple and
      relatively quick and of its familiarity to general neurosurgeons. The tumour
      could be excised radically and extension of anterior, posterior and inferior
      exposure was possible.

PMID- 8748857
TI  - Total intraventricular migration of unisystem ventriculo-peritoneal shunt.
AB  - This is a report of an hydrocephalic adult, in whom a unishunt system migrated
      upwards into the ventricle despite using the appropriate clips (lock and slip).
      The shunt migration discovered 3 months following its insertion. Several
      mechanisms contributed to the migration; negative sucking intra-ventricular
      pressure, positive pushing intra-abdominal pressure, tortuous subcutaneous track
      and neck movements. It seams that lock and slip clips are not enough fixation.
      The best way of preventing such shunt migration is interposing a reservoir
      between the ventricular and peritoneal catheters.

PMID- 8748858
TI  - Some historical notes regarding the launching of the European-Arab courses.

PMID- 8748859
TI  - Microsurgical DREZotomy (MDT) for pain, spasticity, and hyperactive bladder: a 20
      year experience.
AB  - Since 1972, micro-DREZ-tomy has been performed in 367 patients: with cancer pain
      in 81, neurogenic pain in 139, hyperspasticity in 135, and hyperactive neurogenic
      bladder in 12. MDT consists of an incision and bipolar coagulations performed
      ventro-laterally in the Dorsal Root Entry Zone (DREZ) at the entrance of the
      rootlets into the dorso-lateral sulcus. The lesion is directed at 45 degrees
      ventro-medially, and 2-3 mm deep according to the pre-operative neurological
      status and the desired effects. MDT 1 degree interrupts the small (nociceptive)
      fibres regrouped laterally and the large (myotatic) afferents which runs
      centrally, whilst sparing part of the large medial (lemniscal) fibres. 2 degrees
      destroys the (excitatory) medial part of the Lissauer's tract, 3 degrees and the
      cells of the dorsalmost layers of the dorsal horn, which can be the site of
      hyperactivity, as we were able to record in patients with deafferentation pain.
      Best indications are: 1) well localized cancer pain, such as Pan-coast syndrome;
      2) neuropathic pain due to: brachial plexus injuries, cauda equina and/or spinal
      cord lesions especially for pain corresponding to segmental lesions, peripheral
      nerve injuries-amputation-herpes zoster-(especially when the predominant
      component of pain is of the paroxysmal type and/or corresponds to provoked
      hyperalgesia/allodynia); 3) excess of spasticity and 4) neurogenic hyperactive
      bladder.

PMID- 8748860
TI  - Pathogenetic factors in chronic subdural haematoma and causes of recurrence after
      drainage.
AB  - The radiological aspect, pathology, treatment and results of 132 subdural
      haematomas observed in 100 patients, are discussed. The majority of these cases
      were characterized by a nonhomogenous CT scan picture, resulting from repeated
      bleeding in a previous subdural haematoma evolving to chronicity, or in a pre
      existent subdural hygroma. Taking aspirin may have constituted a predisposing
      factor in 16% of our patients, whilst coagulation disturbances, including
      anticoagulant treatment, were observed in another 6%; ethylism was present in
      11%. A traumatic origin was ascertained in 80% of the patients. The treatment
      consisted of burr hole evacuation and drainage in 91.5% of the haematomas,
      corresponding to 92% of the patients; it was eventually repeated once or twice in
      some cases. In 6% of the patients, a subduro-peritoneal drainage had to be placed
      ultimately and in 2%, a membranectomy had to be performed because the haematoma
      had become nearly completely fibrous. The necessity for repeated evacuation and
      eventual subduro-peritoneal drainage seems to depend mainly on a slow brain re
      expansion in some elderly people, who are actually more frequently referred. Two
      patients died; one was deeply comatose and another in poor general condition.
      Morbidity in the 96 remaining patients, 2 being lost to follow-up, was 11%: 5%
      related to the haematoma or to the causal trauma, and 6% from other concomitant
      neurological disease. The functional result was satisfactory in 85%.

PMID- 8748861
TI  - Platelet-activating factor (PAF) and the formation of chronic subdural haematoma.
      Measurement of plasma PAF levels and anti-PAF immunoglobulin titers.
AB  - In order to estimate the contribution of platelet-activating factor (PAF) to the
      formation of chronic subdural haematomas (CSH), we measured plasma PAF and anti
      PAF antibody levels in head-injured patients with and without CSH and normal
      volunteers. Plasma PAF and anti-PAF IgG levels were higher in patients with CSH
      than in patients without CSH or in normal volunteers. Furthermore, plasma PAF and
      anti-PAF IgG levels increased in a time-dependent manner over the first 35 days
      following head injury. These data suggest that PAF may be involved in the
      generation of CSH.

PMID- 8748862
TI  - Bedside measurement of the third ventricle's diameter during episodes of arising
      intracranial pressure after head trauma. Using transcranial real-time sonography
      for a non-invasive examination of intracranial compensation mechanisms.
AB  - Using transcranial real-time sonography, changes in the axial diameter of the
      third ventricle during manoeuvres, which increased intracranial pressure (ICP),
      were measured in 28 patients with moderate to severe head injury. The
      measurements were correlated with ICP measured by epidural pressure monitoring.
      We observed reductions in diameter ranging from 0.3 to 1.1 mm with rises in
      intracranial pressure of at least 5 mm in 22 patients of whom only one died. In 6
      additional patients, no changes in diameter were seen, and 5 of the 6 died. We
      interpret that poor outcome as a measurable inability for the brain to expel
      cerebrospinal fluid into extracerebral compartments during increased ICP.
      Transcranial real-time sonography may provide additional information about
      intracranial cerebral fluid dynamics and compliance.

PMID- 8748863
TI  - Factors influencing the outcome of operative treatment for lumbar spinal
      stenosis.
AB  - 96 patients with lumbar spinal stenosis were operated on after two to sixteen
      years of disabling symptoms. There were 50 women and 46 men with a mean age of 59
      years. 33 of the patients had been previously operated on for spinal complaints.
      A laminectomy was performed in 61 patients; at one level in 31 patients, at two
      levels in 23 patients, and at three levels in seven patients. A hemilaminectomy
      was performed in 35 patients: at one level in 28 patients, at two levels in five
      patients, and at three levels in two patients. There were neither internal
      fixation devices used, nor spondylodesis performed in these operations. Special
      attention was focused on the effect of age, sex, body mass index and smoking, as
      well as previous surgery and extent of surgical intervention on the outcome of
      operative treatment. The follow-up time was 3-11 years (5.5 mean). Laminectomy at
      one level resulted in significantly most acceptable results of operative
      treatment methods. Younger patients and women were more prone to inferior results
      of operative treatment. Also the extent of surgical intervention, overweight and
      smoking seemed to have a tendency to worsen the result of operative treatment.

PMID- 8748864
TI  - Therapy of glioblastoma multiforme: a cumulative experience of 10 years.
AB  - PURPOSE: Comparison of the effect of different therapeutic modalities on survival
      time of patients with glioblastoma multiforme operated on during the last decade
      (1980-1990). PATIENTS AND METHODS: The records of 157 consecutive patients with
      the histological diagnosis of glioblastoma multiforme were analysed for survival
      with respect to age of patients, extent of surgery, influence of re-operation and
      adjuvant postoperative treatment. The latter included fractionated radiotherapy,
      chemotherapy (BCNU. CCNU with Vincristine) and photodynamic therapy (PDT).
      RESULTS: Analysis of variance showed a significant effect for survival after
      macroscopically radical surgery (p = 0.005), postoperative radiotherapy (p <
      0.001), chemotherapy (p < 0.01). Low age (p < 0.05) and a postoperative Karnofsky
      performance score (KPS) > or = 60 (p < 0.001) had a positive influence: the site
      of tumour and pre-operative presence of seizures had no significant influence (p
      > 0.1) on survival time. CONCLUSION: We conclude that the current adequate
      management of glioblastoma multiforme should include surgical resection followed
      by adjuvant treatment such as radiotherapy and chemotherapy.

PMID- 8748865
TI  - Stereotactically-guided craniotomy for cavernous angiomas presenting wit
      epilepsy.
AB  - With the wider availability of magnetic resonance imaging cavernous malformations
      are being recognised with increasing frequency in those patients presenting with
      intractable epilepsy. Surgical resection is the treatment of choice. However,
      because these lesions are usually small and may be located in eloquent areas
      stereotactic resection should be considered. Stereotactically-guided resection of
      pathologically verified cavernous angiograms was performed in 10 patients in this
      series presenting with epilepsy (8 males, 2 females, mean age 32 years). Eight
      patients presented with medically intractable epilepsy (5 complex partial
      seizures, 3 grand mal seizures). Of the remaining patients one experienced
      multiple episodes of haemorrhage and the other headaches (with a non-diagnostic
      scan) both in association with epilepsy. Pre-operative localisation of the motor
      strip was determined in one case by functional MRI. Following resection of these
      lesions all patients experienced improved seizure control with a mean follow-up
      period of 22 months. The mean postoperative hospital stay was 5.1 days with no
      surgical complications recorded. We conclude that stereotactically-guided
      resection offers significant advantages in the management of cavernous
      malformations. Surgical indications for operative resection would include
      medically refractory epilepsy, repeated haemorrhage and those cases where there
      is diagnostic uncertainty.

PMID- 8748866
TI  - Syringomyelia in association with tumours of the posterior fossa.
      Pathophysiological considerations, based on observations on three related cases.
AB  - In this report we describe 3 patients with syringomyelia in association with
      tumours of the posterior fossa. In each patient the syrinx was demonstrated on
      pre-operative magnetic resonance imaging (MRI). After total or partial removal of
      the tumour the syrinx collapsed. It is concluded that the pathogenesis of syrinx
      formation in this entity requires interference with normal cerebrospinal fluid
      (CSF) flow at the foramen magnum. We suggest that the obstruction to the flow of
      CSF causes alterations in the passage of extracellular fluid (ECF) in the spinal
      cord which lead to syringomyelia.

PMID- 8748867
TI  - Monitoring of venous blood flow velocity during interhemispheric approach for
      deep seated lesions.
AB  - No precise intra-operative monitoring of venous blood flow has yet been developed
      for neurosurgical procedures. Preservation of the bridging veins is an important
      issue in order to minimize complications due to disturbances of venous blood flow
      during an interhemispheric approach. In the present study, venous blood flow
      velocity was measured in 11 anterior circulation aneurysms. The measurement was
      performed before brain retraction, during brain retraction and after completion
      of the procedure without brain retraction. In 6 cases, a bridging vein was
      dissected completely free from the dura up to its entry into the superior
      sagittal sinus (SSS group). In 5 cases, dura was cut parallel to the bridging
      vein so that the vein remained covered by the dura (dura group). Venous blood
      flow velocity was measured by microvascular Doppler sonography. The results show
      that venous blood flow can be better preserved during the retraction when the
      bridging vein remains covered with the dura than if the vein is dissected
      completely free from the dura.

PMID- 8748868
TI  - Multimodality electroneurophysiological findings in intra-axial and extra-axial
      lesions of the brain stem.
AB  - In 330 patients with a space occupying lesion of the posterior cranial fossa, the
      blink (BR) and masseter (MR) reflexes and brain stem auditory (BAEP) and
      somatosensory evoked potentials (SEP) were registered. The aim of our study was
      to look for electrophysiological criteria of differentiating between lesions
      within or outside the brain stem. The ipsilateral loss of BAEP in
      cerebellopontine angle tumours and the altered SEP in tumours within the brain
      stem turned out as frequent, almost specific findings. Prolonged ipsi-and
      contralateral late BR responses and prolonged MR responses, a long somatosensory
      central conduction time of the SEP and a prolonged wave III latency as well as a
      prolonged interpeak latency of the BAEP are not indicative but highly suspicious
      for a lesion within the brain stem. Prolonged early responses of the BR together
      with prolonged interpeak latencies of the BAEP are characteristic findings in
      cerebello-pontine angle tumours.

PMID- 8748869
TI  - Are intra- and suprasellar masses detected by CT and MR really tumours?
AB  - The difficulties of differential diagnosis between intra- and suprasellar tumours
      resp. inflammatory processes are discussed, based on three personal cases. In all
      three computed tomography (CT) and magnetic resonance imaging (MR) had
      demonstrated a tumour, but the clinical signs with discrepancies between
      radiological and clinical findings were pointing to an inflammatory process. The
      correct diagnosis of an inflammation was achieved by co-operation between
      neurologist, neurosurgeon, otologist and ophthalmologist. An unnecessary
      neurosurgical operation was avoided and the patients were cured by otological
      intervention and antibiotic therapy.

PMID- 8748870
TI  - Tension pneumocephalus after transsphenoidal surgery: two case reports.
AB  - In this paper, a brief information on factors taking role in intracranial air
      formation and tension pneumocephalus because of two cases epidural air formation
      and tension pneumocephalus following transsphenoidal operation is presented. Two
      cases were treated conservatively.

PMID- 8748871
TI  - Hypotensive effect of nimodipine during treatment for aneurysmal subarachnoid
      haemorrhage.
AB  - To determine the incidence of induced systemic hypotension in patients after
      aneurysmal subarachnoid haemorrhage (SAH) and nimodipine treatment 87 consecutive
      cases were reviewed. The patients were managed according to the same Nimodipine
      treatment protocol. After confirmation of SAH the nimodipine treatment was
      started as a continuous intravenous perfusion at a dosage of 0.5 mg/h and
      gradually increased every 6 hours if haemodynamically tolerated until the
      maintenance dose of 2 mg/h was reached. Median systemic pressure was continuously
      measured and tolerated until a lowest limit of 75 mmHg. In 31 patients (36%)
      hypotension with values below 75 mmHg during at least 30 minutes was noted and
      needed Nimodipine reduction. Intravenous Nimodipine administration was
      responsible for hypotension in 26 cases as compared to 5 cases due to oral
      administration. 38% of all patients required support by vaso-active agents
      (Dopamine or Nor-adrenaline). There was no statistically significant difference
      of incidence of delayed ischaemic deterioration comparing the Nimodipine
      reduction group with the normal dose group. This study demonstrates that a
      considerable risk exists of Nimodipine induced hypotension in intravenous
      administration despite gradually increasing the doses. Correction of hypotension
      through further induced hypervolaemia accompanied by vasoactive agents can lead
      to critical haemodynamic situations. We therefore recommend oral Nimodipine
      administration.

PMID- 8748872
TI  - Influence of aneurysm location on the development of chronic hydrocephalus
      following SAH.
AB  - The incidence of chronic hydrocephalus was analysed in a series of 204 patients
      with aneurysmal subarachnoid haemorrhage (SAH). Its development was significantly
      related to the quantity of subarachnoid blood, but even more to the location of
      the haemorrhage and to the aneurysm site. Hydrocephalus was more frequent in
      patients under poor initial condition. Whereas intracerebral haemorrhage did not
      increase the risk of chronic cerebrospinal fluid (CSF) resorption disturbances.
      Patients with intraventricular haemorrhage or voluminous haemorrhage in the basal
      cisterns have a significantly higher risk of such a complication. In this series
      30 (15%) patients developed chronic hydrocephalus and required shunting.
      Surprisingly, in our series a shunt was never needed in patients with aneurysms
      of the middle cerebral artery (MCA). SAH from an aneurysm of the internal carotid
      artery (ICA) also never caused a shunt-dependent hydrocephalus except in cases
      with accompanying intraventricular haemorrhage. The percentage of chronic
      hydrocephalus was relatively high (19%) in patients with anterior communicating
      artery (ACoA) aneurysms but definitely highest in patients with an aneurysm of
      the vertebrobasilar (VB) system (53%).

PMID- 8748873
TI  - Serial transcranial Doppler study in meningitis.
AB  - Serial transcranial doppler studies were carried out in 12 patients, who
      developed meningitis during their hospital stay. Blood flow velocities in large
      basal vessels of the anterior circle of Willis were correlated with CSF
      pleocytosis and CSF sugar values. Mean blood flow velocities were found to be
      directly proportional to the CSF white blood cell (WBC) count and were inversely
      proportional to the CSF sugar values. Blood flow velocities were higher when CSF
      WBC count was raised. With only one exception these velocities decreased
      progressively with a fall in the CSF WBC count. At the time of meningitis there
      occurred a reduction in CSF sugar values and the blood flow velocities were
      significantly higher. With increase in CSF sugar values there occurred a gradual
      fall in the blood flow velocities.

PMID- 8748874
TI  - Intracranial mycotic infections in neurosurgical practice.
AB  - Intracranial mycotic infections requiring neurosurgical intervention are being
      diagnosed more frequently. This study is a review of 17 cases of intracranial
      mycotic infections that were treated in a neurosurgical unit in Saudi Arabia over
      an 8-year period. A primary focus of infection was identified in 41% of patients
      while 18% of patients had a predisposing factor. Forty-seven percent of patients
      presented with a brain abscess (solitary 29%, multiple 18%) while 35% had a
      granuloma. 18% meningitis and ventriculitis and 12% hydrocephalus. The
      Aspergillus species and Ramichloridium machenziei were the commonest pathogens.
      Following the appropriate surgical and antimicrobial treatment, the mortality
      rate was 41% and there was evidence of residual disease at follow-up in 18%. The
      reason for a fatal outcome was failure to consider a fungal aetiology and to
      obtain a tissue diagnosis early-because of late referral (2 cases), as well as
      failure to respond to antimycotic therapy (4 cases) and rupture of the internal
      carotid artery due to Aspergillus arteritis (one case). It is concluded that an
      early tissue diagnosis is crucial in the management of intracranial mycotic
      infection so that the appropriate surgical and antimycotic treatment can be
      started early.

PMID- 8748875
TI  - The blink reflex before and after percutaneous glycerol rhizotomy in patients
      with trigeminal neuralgia--a prospective study of 28 patients.
AB  - The blink reflex was prospectively studied in 28 patients with trigeminal
      neuralgia, prior-to and following percutaneous glycerol rhizotomy to the
      Gasserian ganglion. Fifteen patients (54%) had varying degrees of sensory loss in
      the trigeminal nerve distribution already before glycerol injection. Three more
      patients developed sensory loss following glycerol injection. Thus following
      glycerol injection 18 patients had graded sensory loss. Pre-injection the blink
      reflex showed abnormal R1 wave in 57% patients, while direct and consensual R2
      waves were abnormal in 43% and 48%, respectively. Post-injection R1 wave was
      abnormal in 64% patients. Direct R2 waves were abnormal in 33% patients. Thus
      clinical findings of sensory loss correlated well with pre-and post-injection
      blink reflex abnormality. Postoperatively R1 and ipsilateral R2 latencies from
      the side of the injection deteriorated and consensual R2 latency improved, thus,
      signifying better function on the contralateral side following relief of pain by
      glycerol rhizotomy.

PMID- 8748876
TI  - Stable prostacyclin improves postischaemic microcirculatory changes in
      hypertensive rats.
AB  - The prostacyclin analogue TTC-909 is incorporated in lipid microspheres and is
      chemically very stable. We examined the efficacy of TTC-909 on cerebral
      microcirculation following focal cerebral ischaemia. Focal cerebral ischaemia was
      produced by the occlusion of the distal middle cerebral artery in stroke-prone
      spontaneously hypertensive rats. Intravenous administration of TTC-909 (100
      ng/kg/day) or vehicle was started 30 minutes after the occlusion and repeated for
      7 days. On day 7, cerebral blood flow and blood-brain barrier permeability were
      measured autoradiographically. Brain oedema was estimated by the gravimetric
      method. The size of the infarction was calculated from area measurements on
      serial histologic sections. Treatment with TTC-909 resulted in significant
      improvement in regional blood flow in the ischaemic rim (p < 0.01) and the
      surrounding area (p < 0.05). With TTC-909 treatment, the increased permeability
      was significantly reduced in the ischaemic centre (p < 0.01) and rim (p < 0.05).
      A decrease in specific gravity in the ischaemic region and the remote non
      ischaemic regions was prevented by the treatment (p < 0.01). We assumed that the
      efficacy of TTC-909 maintains the blood supply in the ischaemic area, improves
      disruption of the blood-brain barrier and prevents development of ischaemic
      oedema.

PMID- 8748877
TI  - Stereo-videomicrography projection system for use at scientific meetings. A
      technical note.
AB  - A new stereoscopic projection system has been developed for simultaneous viewing
      of microsurgical procedures by hundreds of participants at neurosurgical
      meetings. The video images recorded from each eyepiece of an operating microscope
      were projected onto two wide screens, which were viewed by two converging eyes or
      by cross-sight. The system was simple and proved to be of great practical use
      although it yielded minor eyestrain and required some practice.

PMID- 8748878
TI  - Direct approach to intracranial vertebral arteriovenous fistula. Case report.
AB  - A case of intracranial vertebral arteriovenous fistula is reported. The treatment
      of choice for this particular vascular malformation is controversial because of
      the difficulty of management of the intracranial portion of the lesion. We here
      report a case treated successfully by direct surgery. Its anatomical delineation
      and operative approach are discussed.

PMID- 8748879
TI  - A super long-acting LH-RH analogue induces regression of hypothalamic hamartoma
      associated with precocious puberty.
AB  - We treated a 1-year-old female with a hypothalamic hamartoma and precocious
      puberty with leuprolide acetate depot, a super long-acting hormone-releasing
      hormone analogue (Tap-144-SR; [D-Leu6-[des-Gly10-NH2] LH-RH ethylamide acetate).
      The infant's major symptoms were genital bleeding and gynaecomastia. The LH-RH
      analogue (30 micrograms/kg) was injected subcutaneously once every 4 weeks.
      Clinical and laboratory manifestations of precocious puberty showed marked
      improvement. A follow-up after 16 months of treatment, the size of the tumour
      decreased significantly and remained unchanged for 2 years of further follow-up.
      To the best of our knowledge, this is the first hypothalamic hamartoma case in
      whom a decrease of tumour size under treatment with LH-RH analogue has been
      documented. But, because diagnosis of hamartoma is only based on
      neuroradiological and not on histological examinations, the possibility of a
      gangliocytoma cannot be excluded with certainty.

PMID- 8748880
TI  - Chronic anterior pallidal stimulation for Parkinson's disease.
AB  - We present the case of a 51-year-old female who had a four-year history of
      Parkinson's disease with severe "on-off' and disabling progression of symptoms on
      chronic levodopa therapy. After obtaining FDA approval, we implanted a Medtronic
      deep brain stimulation lead stereotactically into the right anterior pallidum
      contralateral to her most symptomatologic side. Intra-operative stimulation
      trials at 100 Hz caused reproducible reversal of akinetic symptoms and
      simultaneous microelectrode recording of the posteroventral pallidum revealed
      decreased neural activity during anterior pallidal stimulation. The patient was
      evaluated pre-operatively and postoperatively using the Hoehn and Yahr Staging
      Scale, the Unified Parkinson's Disease Rating Scale (UPDRS), videotape, and a
      computerized data glove. Six months after implantation, the total UPDRS score was
      decreased from 68 to 8 and Hoehn and Yahr Staging improved from 3.0 to 1.5 during
      periods of chronic high frequency stimulation. Dramatic improvements in tremor,
      dystonia, bradykinesia, and akinesia were noted within seconds of stimulator
      activation and were also objectively measured using a computerized data glove.
      This case reveals the potential for therapeutic pallidal stimulation for
      Parkinson's akinetic symptomatology.

PMID- 8748881
TI  - Symptomatic intraventricular arachnoid cyst in an elderly man.
AB  - A case of intraventricular arachnoid cyst in an elderly man is reported. A 63
      year-old man developed a progressive gait disturbance over a five-year period. CT
      scan showed a large cyst in the left lateral ventricle which was negative to
      contrast enhancement. CT cisternography revealed gradual accumulation and more
      than 48 hours retention of contrast medium in the cyst. The patient underwent
      left frontal craniotomy, and the cyst wall was partially resected for
      histopathological examination. Although limit microscopic examination could not
      establish a diagnosis, arachnoid cyst was diagnosed by electron microscopic
      findings. Biochemical analysis did not detect any difference between cyst fluid
      and CSF obtained during surgery. It is suggested that a ball-valve mechanism
      caused progressive enlargement of the cyst and gradual development of symptoms in
      this elderly patient.

PMID- 8748882
TI  - Microcirculation in venous disorders: the role of the white blood cells.
AB  - The haemodynamic hallmark of chronic venous disease in the legs is raised
      ambulatory venous pressure. This is probably the principal cause of both the
      symptoms of long-standing varicose veins and the trophic changes round the ankle
      characteristics of chronic venous insufficiency, presumably by an effect on the
      microcirculation. The microcirculatory consequences of raised venous pressure
      include morphological changes, as well as functional abnormalities ranging from
      haemorheological changes, increased capillary permeability and abnormalities of
      fibrinogen metabolism to trapping of white blood cells in the dependent legs.
      This last is now known to be accompanied by sequestration of platelets, which is
      irreversible. It is postulated that leucocyte activation releases cytokines,
      leucocyte-derived oxygen free radicals, proteolytic enzymes and platelet
      activating factor. It has been shown that external compression not only relieves
      stasis but also decreases white cell trapping. A strategy for management of the
      complications of venous disease should therefore be aimed at treatment of both
      the macrocirculatory haemodynamic defect and the microcirculatory abnormalities.
      The latter is an ideal target for systemic pharmacotherapy.

PMID- 8748883
TI  - Microcirculatory models of ischaemia-reperfusion in skin and striated muscle.
AB  - Intravital microscopy is used for analysis of the microcirculation in various
      organs, e.g. mesentery, intestine, heart, liver and lung, requiring either
      exteriorization or in situ visualization techniques in anaesthetized animals. In
      contrast, the implantation of transparent chambers has been employed to allow
      chronic observation of the microcirculation in intact, non-anaesthetized animals.
      This paper reports results with two transparent chamber models: the skin-fold
      chamber model in the hamster and the mouse. An overview is provided of the
      technical development of the chamber technique and of the various experimental
      studies that have been performed using these models in ischaemia-reperfusion of
      striated muscle. Particular emphasis is given to a description of the methods
      used to induce ischaemia and reperfusion, namely pressure-induced or tourniquet
      induced ischaemia. While the former allows simulation of the pathophysiological
      situation in compartment syndromes, the latter provides an appropriate simulation
      of the clinical situation in vascular, transplantation and reconstructive
      surgery. Future possibilities for these microcirculation models in research into
      the pathophysiology of ischemia-reperfusion are outlined, and potential
      therapeutic measures to preserve postischaemic tissue are discussed.

PMID- 8748884
TI  - Cellular basis of inflammation, edema and the activity of Daflon 500 mg.
AB  - Inflammation activates leukocytes causing the release of agents that disrupt the
      endothelial barrier to such an extent that retention of plasma protein is
      impaired. This phenomenon can be observed using microvascular methods in which
      ischemia-reperfusion-induced inflammation-like condition are analyzed in terms of
      the increased adherence of leukocytes to the venular endothelium. Pretreatment
      with Daflon 500 mg, a purified, micronized, flavonoid fraction consisting of 90%
      diosmin and 10% hesperidin, prior to the induction of 4 h of tourniquet ischemia
      significantly lowers the number of adherent leukocytes. This observation is
      linked to the protective effect of flavonoids in the treatment of edema, as
      decreased activation is also associated with a decreased platelet and complement
      system activation, leading to a lowered release of histamine and decreased
      leukocyte-dependent endothelial damage. It is proposed that attenuation of
      leukocyte adherence during ischemia-reperfusion is evidence of the protective
      endothelial effect of Daflon 500 mg and its ability to control edema in clinical
      situation.

PMID- 8748885
TI  - Effects of Daflon 500 mg on increased microvascular permeability in normal
      hamsters.
AB  - Daflon 500 mg1 (S 5682) is a purified, micronized, flavonoid fraction containing
      90% diosmin and 10% hesperidin, which is currently used to treat chronic venous
      insufficiency and haemorrhoidal disease. In the present study, the effects of
      Daflon 500 mg on increased microvascular permeability induced by histamine,
      bradykinin and leukotriene B4 (LTB4) were investigated by intravital microscopy
      in the hamster cheek pouch preparation. Daflon 500 mg, suspended in 10% lactose
      solution, or vehicle (10% lactose) was administered orally to male hamsters for
      10 days at a dose of 20 mg/kg/day (10 mg/kg twice daily). Fluorescein
      isothiocyanate-labeled dextran 150 was given intravenously, 30 min after
      completion of the cheek pouch preparation. Histamine, 2 mumol/l, bradykinin, 0.1
      mumol/l, and LTB4, 0.01 mumol/l, applied topically for 5 min increased the number
      of fluorescent vascular leakage sites in postcapillary venules. The maximum
      number of leaky sites per cm2 in the prepared area that occurred 5 min after the
      beginning of each topical application was quantified by UV light microscopy. In
      comparison with vehicle, Daflon 500 mg significantly inhibited the macromolecular
      permeability-increasing effect of histamine (343.5 +/- 22.3 vs. 207.5 +/- 32.0; p
      < 0.01), bradykinin (345.2 +/- 19.0 vs. 206.2 +/- 21.6; p < 0.01) and LTB4 (353.3
      +/- 27.5 vs. 242.7 +/- 33.6; p < 0.05). These results demonstrate that oral
      administration of Daflon 500 mg for 10 days at 20 mg/kg body weight/day has a
      protective effect against leakage of macromolecules after application of
      permeability-increasing substances in the cheek pouch microvasculature. These
      data, which illustrate the inhibitory effect of a clinically relevant dose of
      Daflon 500 mg on the inflammatory processes induced in this in vivo model of
      microcirculation, may serve as a rational basis to explain the clinical efficacy
      of Daflon 500 mg.

PMID- 8748886
TI  - Effect of Daflon 500 mg, a flavonoid drug, on neurological signs, levels of free
      radicals and electroretinogram in the gerbil after ischemia-reperfusion injury.
AB  - The effect of Daflon 500 mg1, purified, micronized flavonoid fraction (90%
      diosmin, 10% hesperidin) was studied on stroke index, levels of free radicals and
      electroretinography in the gerbil after ischemia-reperfusion injury. The drug was
      administered orally at doses of 200, 100 and 50 mg/kg, for 6 days before left
      carotid occlusion. Daflon 500 mg significantly reversed the increase of stroke
      index only at the dose of 100 mg/kg and significantly decreased levels of
      hydroxyl free radicals at all 3 doses with a maximum effectiveness for the dose
      of 100 mg/kg. Amplitude and latency of the b wave were disturbed after ischemia
      reperfusion insult. Daflon 500 mg, 100 mg/kg for 6 days, significantly reversed
      these modifications. In conclusion, Daflon 500 mg could interact with hydroxyl
      free radicals, which have a deleterious effect in ischemic tissues, particularly
      in the retina.

PMID- 8748887
TI  - Advances in microcirculation network evaluation: an update.
AB  - Many methods are available today for clinical evaluation of the blood supply to
      an extremity or part of an extremity, some of which are excellent for determining
      the presence and severity of arterial and venous disorders. These methods,
      however, do not give any information on the microvascular status of the diseased
      areas. This is particularly true for the skin circulation, which has a rather
      complex vascular network with nutritional and thermoregulatory vessels,
      arteriovenous shunts, etc. The most useful method for clinical evaluation of the
      skin capillary circulation is vital capillary microscopy. The skin capillaries in
      an area with a reduced microcirculation change in structure, and it is possible
      to evaluate the viability of the skin by microscopic studies of these capillary
      changes. Both morphology and blood flow can be investigated. By using different
      intravital fluorescent dyes, e.g. sodium fluorescein and indocyanine green, the
      microvascular dynamics, flow distribution and microvascular permeability can also
      be studied. The total skin microcirculation can be evaluated by Laser Doppler
      fluxmetry, which measures primarily the blood flow in the thermoregulatory
      vascular bed, i.e. the subpapillary arterial and venous plexa. It is easy to use
      in clinical practice, but interpretation of the results can sometimes be
      difficult. Measuring transcutaneous oxygen tension has for many years been used
      in clinical routine to evaluate the viability of skin in patients with vascular
      disorders. It has recently been shown that inhalation of oxygen may induce
      vasoconstriction in healthy subjects and in patients with moderate arterial
      insufficiency, but an increase of the skin microcirculation in areas of severe
      ischaemia. By using different combinations of the above mentioned
      microcirculatory techniques, valuable information can be gained regarding
      pathophysiological phenomena of the microcirculation in many diseases, e.g.
      vascular disorders, collagenosis. Raynaud's phenomenon, diabetes and
      hypertension. Using techniques for both macro- and microcirculation is also of
      great importance for evaluating the effect of therapeutic procedures in several
      of these disorders.

PMID- 8748888
TI  - Intravital capillaroscopy in patients with chronic venous insufficiency and
      lymphoedema: relevance to Daflon 500 mg.
AB  - Microangiopathy of chronic venous insufficiency is characterized by elongated,
      dilated and coiled skin capillaries, which are surrounded by an enlarged
      pericapillary space (halo). Reduction of capillary number and even areas devoid
      of microvessels (atrophie blanche) are common in severe chronic venous
      insufficiency associated with focal microvascular ischaemia (decreased
      transcutaneous oxygen tension). The superficial network of skin lymphatic
      capillaries is obliterated in part. Oedema formation results from increased
      permeability of blood capillaries (enhanced transcapillary diffusion of sodium
      fluorescein) and deficient lymphatic drainage of interstitial fluid.

PMID- 8748889
TI  - Laser Doppler and transcutaneous oximetry: modern investigations to assess drug
      efficacy in chronic venous insufficiency.
AB  - During chronic venous insufficiency (CVI), microcirculatory changes, e.g. a
      decrease in transcutaneous oxygen pressure (tcpO2) and an increase in
      transcutaneous carbon dioxide pressure (tcpCO2), are implicated in the
      pathophysiology of trophic disorders leading ultimately to venous ulcers. Daflon
      500 mg1, a micronized purified flavonoid fraction, has been shown to improve
      venous tone, capillary permeability and resistance, and lymphagogue activity at a
      daily dose of 2 tablets. To assess the effects of Daflon 500 mg on
      microcirculatory parameters by means of laser Doppler fluxmetry and
      transcutaneous oxiketry, a 3-month, double-blind, randomized, parallel-group
      study was carried out in 104 patients divided into 3 groups according to the
      daily dose: 1 tablet (group 1, n = 34), 2 tablets (group 2, n = 33), on 4 tablets
      (group 3, n = 37). All patients (mean age 43.7 +/- 13.1 years; 100 females, 4
      males) included in the study were affected by mild CVI. They were followed for 90
      days with visits at 1 month (day 28) and 3 months (day 90). At inclusion, there
      were no significant differences between groups as regards biometric data, mean
      tcpO2 (group 1, 62.7 +/- 4.5 mm Hg; group 2, 64.0 +/- 3.3 mm Hg; group 3, 64.1 +/
      3.5 mm Hg), mean tcpCO2 (group 1, 40.7 +/- 2.5 mm Hg; group 2, 39.3 +/- 2.9 mm
      Hg; group 3, 40.0 +/- 2.5 mm Hg) and laser Doppler parameters. Fourteen patients
      withdrew from the study (group 1, n = 4; group 2, n = 3; group 3, n = 7): 9 for
      reasons not related to treatment, 3 for adverse events, 2 because they were lost
      to follow-up. From day 0 to day 90, mean tcpO2 significantly increased (p <
      0.001) in each group (group 1, 3.0 +/- 2.1 mm Hg; group 2, 2.9 +/- 2.1 mm Hg;
      group 3, 2.5 +/- 1.6 mm Hg), mean tcpCO2 significantly decreased (p < 0.001) in
      each group (group 1, 2.6 +/- 2.0 mm Hg; group 2, 1.7 +/- 1.9 mm Hg; group 3, 2.2
      +/- 1.5 mm Hg). No significant differences were observed between groups. Laser
      Doppler parameters remained unchanged from day 0 to day 90 in the 3 groups.
      Symptoms (discomfort, pain, heaviness, burning sensation) and signs (oedema) of
      CVI as well as perimetric measurements of calf and supramalleolar area were
      significantly improved in the 3 groups. In conclusion, during this 3-month study,
      Daflon 500 mg improved oximetric measurements and did not alter laser Doppler
      parameters. These data suggest that Daflon 500 mg, at the early stages of CVI,
      acts favourably on the microcirculatory disturbances also involved in the
      pathophysiology of more severe stages of CVI.

PMID- 8748890
TI  - An original microhaemorheological approach to the pharmacological effects of
      Daflon 500 mg in severe chronic venous insufficiency.
AB  - In the more advanced stages of chronic venous insufficiency, stasis in the skin
      microcirculation is associated with a decreased red blood cell velocity and an
      increase in packed cell volume related to the red blood cell piling phenomenon.
      Although the main factor determining blood viscosity is packed cell volume, the
      direct relationship between this variable, viscosity and velocity is no longer
      valid at the microcirculatory level (sigma effect). Viscosity is influenced by
      blood composition and red blood cell deformability. The aim of this open pilot
      study was to verify the variations in capillary packed cell volume in comparison
      with the velocity in 24 patients with third-stage chronic venous insufficiency
      before (day 1) and after (day 28) a 28-day treatment with Daflon 500 mg, a
      micronized purified flavonoid fraction consisting of diosmin, 450 mg, and
      hesperidin, 50 mg, per tablet, 1 g/day, and then 14 days (day 42) after cessation
      of treatment. Ankle skin microcirculation was evaluated by dynamic
      capillaroscopy. Values of relative capillary packed cell volume were calculated
      by a densitometric method, and red blood cell velocity was calculated using the
      cross-correlation simplified method. Relative capillary packed cell volume (mean
      +/- SD) significantly (p = 0.001) increased from day 1 (64.10 +/- 9.34%) to day
      28 (72.89 +/- 5.74%) and then decreased until day 42 (66.84 +/- 7.48%). In the
      same patients, red blood cell velocity (mean +/- SD) significantly (p = 0.041)
      increased from day 1 (0.26 +/- 0.14 mm/sec) to day 28 (0.35 +/- 0.11 mm/sec) and
      then remained stable until day 42 (0.33 +/- 0.16 mm/sec). Two possible
      explanations can account for this apparent discrepancy: first, dissociation
      between viscosity and velocity due to the Fahraeus-Lindqvist effect (sigma
      effect); and secondly, increased deformability of red blood cells leading to an
      increased red blood cell velocity despite an increased packed cell volume. It can
      be concluded that Daflon 500 mg seems to have a beneficial haemorheological
      effect, resolving the stasis with an increase in red blood cell velocity. A
      concomitant increase in relative packed cell volume and red blood cell velocity
      after therapy suggests an improvement of the flexibility of red blood cells.

PMID- 8748892
TI  - MRI of pineal region tumours: relationship between tumours and adjacent
      structures.
AB  - A variety of tumours may arise in the pineal region; accurate diagnosis is
      important in the selection of treatment and prognosis. A retrospective analysis
      of the MRI studies of 25 patients with pathologically proven pineal region
      tumours was performed, focused on the relationship between the tumour and
      neighbouring structures. Compression of the tectal plate was classified as
      expansive or invasive, and compression of the corpus callosum as inferior,
      anterior or posterior. In 10 of the 14 patients (71%) with germ cell tumours
      tectal compression was of the invasive type; 8 patients (57%) had multiple
      tumours and in 13 (93%) the tumor margins were irregular. Teratomas were readily
      diagnosed because of characteristic heterogeneous signal intensity. Pineal cell
      tumours were differentiated from germ cell tumours by their rounded shape, solid
      nature, sharp margins, and expansive type of tectal compression. Meningiomas were
      characterised by their falcotentorial attachments, posterior callosal
      compression, and a low-intensity rim on T2-weighted images. Gd-DTPA injection
      enabled clear demonstration of the site and extent of tumour spread and was
      useful in differentiating cystic and solid components. The appearances described,
      while not pathognomonic, are helpful in the differential diagnosis of pineal
      region tumours, and valuable in planning appropriate treatment.

PMID- 8748891
TI  - 1H and 31P magnetic resonance spectroscopic imaging of white matter signal
      hyperintensity areas in elderly subjects.
AB  - White matter signal hyperintensities (WMSH) are commonly seen on MRI of elderly
      subjects. The purpose of this study was to characterize metabolic changes in the
      white matter of elderly subjects with extensive WMSH. We used water-suppressed
      proton (1H) magnetic resonance spectroscopic imaging (MRSI) to compare six
      subjects with extensive WMSH with eight age-matched elderly subjects with minimal
      or absent WMSH, and phosphorus (31P) MRSI to compare nine subjects with extensive
      WMSH and seven age-matched elderly subjects without extensive WMSH. Relative to
      region-matched tissue in elderly controls, extensive WMSH were associated with
      increased signal from choline-containing metabolites, no significant change of
      signal from N-acetylaspartate, and a trend to a decreased phosphomonoester (PME)
      resonance. These findings suggest that WMSH may be associated with an alteration
      of brain myclin phospholipids in the absence of axonal damage. There were no
      differences in energy phosphates, consistent with lack of ongoing brain ischemia.
      Within the group with extensive WMSH, PME resonance measures were significantly
      lower in WMSH than in contralateral normal-appearing white matter. These results
      provide information on pathophysiology of WMSH and a basis for comparison with
      WMSH in Alzheimer's disease, vascular dementia, multiple sclerosis, and other
      diseases.

PMID- 8748893
TI  - Tissue characterisation of atherosclerotic carotid plaques by MRI.
AB  - Carotid artery plaques with intraplaque haemorrhage or atheromatous debris have
      been found to be associated with an increased risk of embolic stroke. Other
      methods have failed to detect plaque morphology, and it is not clear whether MRI
      allows differentiation between prognostically and therapeutically relevant plaque
      types. We examined 17 carotid bifurcation plaques which had been removed in toto
      by MRI. For quantifying MR signal intensities (I) the contrast-to-noise ratio
      (CNR) was used: (ITissue-IRef)/SDRef, with normal saline (0.9%) as reference
      (Ref) and the standard deviation (SD) of the noise. Measurements were correlated
      with the histopathological appearance of "simple plaques", consisting of fibrous
      intimal thickening, lipid deposits and/or atheromatous tissue with cholesterol
      crystals, largely calcified plaques, and "complicated plaques", containing recent
      intramural haemorrhage or friable atheromatous debris. Significantly different
      mean CNR could be measured in the three plaque types on T1- and T2-weighted
      sequences (p < 0.00001) and using the FLASH pulse sequence with a flip angle of
      15 degrees (p < 0.001). With the T1-weighted sequence simple plaques showed a CNR
      of 4.4 +/- 2.3, calcified plaques -4.8 +/- 2.6 and complicated plaques 15.1 +/-
      4.3. Using this technique, each single plaque could be correctly classified, an
      unalterable prerequisite for a clinical application. To date, motion artefacts
      due to patient movement or insufficiently triggerable vessel pulsation in
      combination with relative long acquisition times (6-7 min) have limited in vivo
      investigations. If these problems could be overcome, MRI might become a valuable
      technique for studying carotid plaque morphology.

PMID- 8748894
TI  - Paracoccidioidomycosis of the central nervous system: CT findings.
AB  - A retrospective analysis of six cases of central nervous system
      paracoccidioidomycosis, all but one proven by biopsy and surgery, was carried out
      to study the CT and clinical data and pathological correlation. Most of the
      patients were from the country. Headache, vomiting, seizures and hemiparesis were
      the most frequent symptoms. Papilloedema was present in four patients with raised
      intracranial pressure. Five patients had chronic lung disease and two with
      advanced systemic disease, skin and mucous membrane lesions were also observed.
      The neurological disturbance was sometimes the presenting features and the
      diagnosis was discovered incidentally after surgery. Both solitary and multiple
      parenchymal lesions were observed and the cerebral hemispheres were more commonly
      involved in four patients. Local meningeal involvement was observed in one with a
      single cortical granuloma. We emphasise the usefulness of CT, showing a rounded
      or lobulated mass with an isodense or radiolucent centre after contrast
      enhancement, surrounded by an irregular wall of varying thickness. There was
      always moderate oedema, extending peripherally. Other infections or neoplastic
      diseases may present similar findings. Preoperative diagnosis should rest on
      integration of clinical data, chest films, laboratory and neuroimaging studies.

PMID- 8748895
TI  - Focal cortical hypoperfusion in corticobasal degeneration demonstrated by three
      dimensional surface display with 123I-IMP: a possible cause of apraxia.
AB  - To clarify cortical lesions responsible for apraxia in cortico-basal degeneration
      (CBD), we reconstructed three-dimensional surface images from single-photon
      emission computed tomography (SPECT) data with N-isopropyl-p[I-123]
      iodoamphetamine in two patients with CBD. Both had limb-kinetic apraxia (LKA) and
      one also had constructional apraxia (CA). Both showed asymmetrical cortical
      hypoperfusion in the perirolandic area. The patient with CA had unilateral
      hypoperfusion in the posterior parietal area. Thus, cortical hypoperfusion in the
      perirolandic area corresponded to LKA, and that in the posterior parietal area to
      CA.

PMID- 8748896
TI  - Recovery from primary deep cerebral venous sinus thrombosis with recanalisation.
AB  - A 50-year-old woman with idiopathic deep cerebral sinus and vein thrombosis
      (DCVT) had cerebellar disturbance prior to impaired consciousness. CT and MRI
      revealed haemorrhagic infarction in the cerebellum and signal changes suggesting
      infarction in the thalamus and basal ganglia bilaterally. The straight sinus and
      internal cerebral vein (ICV) were dense on CT. On angiography, the vein of Galen
      (VG) and straight sinus were not seen. Following clinical recovery, CT and MRI
      became normal, and angiography showed recanalization of the VG and ICV. The
      relationship between cerebellar infarction and DCVT, and signal changes on CT and
      MRI are discussed.

PMID- 8748897
TI  - Carmofur-induced leukoencephalopathy: MRI.
AB  - Carmofur, a derivative of 5-fluorouracil, has recently been noted to have an
      infrequent but serious association with leukoencephalopathy. To our knowledge,
      there has been no report of early MRI findings in this leukoencephalopathy. We
      describe a case in which diffuse high signal intensity of the entire cerebral
      white matter, including the corpus callosum, was seen on T2-weighted magnetic
      resonance images. Although similar findings can be seen in many other diseases,
      carmofur-induced leukoencephalopathy should be suspected in a patient treated
      with carmofur. It is important to know the clinical and MRI characteristics of
      this condition, for early diagnosis and better prognosis.

PMID- 8748898
TI  - Intracranial subdural dissemination of germ cell tumour producing human chorionic
      gonadotrophin.

PMID- 8748899
TI  - Bilateral aberrant internal carotid arteries.
AB  - An aberrant course of the internal carotid artery is a rare vascular anomaly.
      This is the only known reported case of bilateral aberrant internal carotid
      arteries examined with CT and MRI.

PMID- 8748900
TI  - Anomalous origin of the calcarine artery.

PMID- 8748901
TI  - Pontine haemorrhage causing disturbance of taste.

PMID- 8748902
TI  - Laminectomy-induced arachnoradiculitis: a postoperative serial MRI study.
AB  - Time-related changes of laminectomy-induced cauda equina adhesions were
      investigated by MRI in ten patients with degenerative spinal disease who
      underwent posterior surgery to the lumbar spine; seven had disc herniations and
      three spinal stenosis. Axial MRI was performed before and 3, 7, 21 and 42 days
      after surgery. Cauda equina adhesions were most severe at the laminectomised
      levels L3-4, L4-5 and L5-S1 (n = 16); partial adhesions were found in 9 of 16
      levels at 6 weeks after surgery. At the L3-4 or L5-S1 levels (n = 14), the area
      of laminar exposure without laminectomy, the cauda equina adhesions continued 1
      week after surgery, but thereafter resolved; only partial adhesions were seen at
      5 of 14 levels 6 weeks after surgery. Shrinkage of the arachnoid sac was also
      found at the level of the laminectomy, but it re-expanded 3 weeks after surgery
      in all cases. Cauda equina adhesions and shrinkage of the sac were correlated
      closely with laminectomy, with or without discectomy, suggesting that an
      inflammatory process of deep wound healing may be involved in the mechanism of a
      laminectomy-induced arachnoradiculitis which may be correlated with post
      operative leg symptoms.

PMID- 8748903
TI  - Association of transverse ligament calcification with anterior atlanto-odontoid
      osteoarthritis: CT findings.
AB  - The craniocervical junction was assessed in 700 consecutive unselected patients
      undergoing CT of the brain or paranasal sinuses, to investigate whether
      transverse ligament calcification was associated with advanced degenerative
      changes at the anterior atlanto-odontoid (AO) joint. Calcific deposits within the
      transverse ligament were seen in 40 patients (5.7%). The prevalence of this
      condition increased with age. Advanced degenerative changes (marked osteophytes
      and obliteration of the joint space) at the anterior AO joint were significantly
      more frequent in patients with transverse ligament calcification than in age
      matched controls. We conclude that transverse ligament calcification is seen
      frequently in the elderly and very frequently with advanced degenerative changes
      at the anterior AO joint.

PMID- 8748904
TI  - Reversibility of lumbar epidural lipomatosis in obese patients after weight
      reduction diet.
AB  - We present three obese patients with symptomatic lumbar epidural lipomatosis. All
      three were treated with a calorie-controlled diet and considerable weight
      reduction was achieved. MRI demonstrated a reduction in the epidural fat and
      relief of thecal sac compression in all three; two also improved clinically.

PMID- 8748905
TI  - Peculiar enlargement of the nasopharynx in patients with anorexia nervosa.
AB  - We examined the nasopharynx and brain in 17 patients with anorexia nervosa by CT
      and compared the findings with those of 44 normal subjects and of 5 patients of
      the same age with marked emaciation caused by various psychiatric disorders. An
      enlarged nasopharyngeal space with a flattened posterior wall and enlarged
      lateral pharyngeal recesses were demonstrated in all patients with anorexia
      nervosa whose weight was lowest at the time of the CT examination, and these CT
      features regressed or became normal quickly after they had gained some weight.
      This characteristic enlargement of the nasopharynx and lateral pharyngeal
      recesses was observed neither in the markedly emaciated patients (2 with
      schizophrenia, 1 with major depression, 1 with stupor and the other with an
      extremely unbalanced diet) nor in 44 normal subjects without emaciation. These
      features were therefore thought to be characteristic and of diagnostic
      significance.

PMID- 8748906
TI  - Leukoencephalopathy with swelling in children and adolescents: MRI patterns and
      differential diagnosis.
AB  - In children, several neurological disorders are characterised by spongiform
      leukoencephalopathy. MRI of the brain typically shows white matter swelling, but
      does not enable differentiation of the various underlying disorders. The aim of
      this article is optimisation of the diagnostic value of MRI in
      leukoencephalopathy accompanied by swelling. MRI-based inclusion criteria were
      met by 20 patients in our database. The images were analysed using a detailed
      scoring list. In 13 of the 20 patients the clinical diagnosis was known (11
      definite and 2 probable diagnoses). Characteristic MRI abnormalities could be
      defined in these patients. Of the 7 patients without a diagnosis, 5 had identical
      MRI abnormalities: diffuse hemisphere swelling and typical cysts in
      frontoparietal subcortical white matter and the tips of the temporal lobes. The
      clinical picture was also similar in these patients, suggesting a similar
      disease.

PMID- 8748907
TI  - Randomised double-blind clinical trial of intermediate- versus high-dose chloral
      hydrate for neuroimaging of children.
AB  - Orally administered chloral hydrate is the most widely used sedative in children
      undergoing MRI. We compared intermediate- and high-dose oral chloral hydrate in
      97 consecutive children undergoing MRI in a prospective, controlled, double
      blind, randomised clinical trial. There were 50 girls and 47 boys, mean weight
      (+/- SD) 14.7 +/- 6.4 kg, and mean age 38 +/- 31. The children were randomly
      allocated to receive chloral hydrate syrup either 70 mg/kg (group A, n = 50) or
      100 mg/kg (group B, n = 47). These two groups were not significantly different in
      sex, weight, age, diagnosis or ambulatory medication. The mean initial dose (+/-
      SEM) was 64 +/- 2 mg/kg for group A and 93 +/- 2 mg/kg for group B. Because
      adequate sedation was not achieved, 14 patients in group A and 6 in group B
      required a second dose, giving a mean total dose of 70 +/- 2 mg/kg for group A
      and 96 +/- 2 mg/kg for group B. The percentage of successful examinations after
      the initial dose (A: 64%, B: 87%; p < 0.05) and the total dose (A: 92%, B:100%; p
      = 0.14) was higher in group B. Significant differences were found for the time of
      onset of sedation (A:28 +/- 2 min, B: 21 +/- 1 min; p < 0.05), but not for the
      time to spontaneous awakening after the completion of the examination. The rate
      of adverse reactions was similar (A: 20%, B: 21%; p = 1.00). We conclude that
      high-dose oral chloral hydrate improves the management of children undergoing
      MRI.

PMID- 8748908
TI  - Facial haemangioma, agenesis of the internal carotid artery and dysplasia of
      cerebral cortex: case report.
AB  - We describe a girl with a facial haemangioma, associated with other vascular
      anomalies: agenesis of the internal carotid artery, cerebral cortical dysplasia
      and hypoplasia of the cerebral hemisphere on the same side of the angioma. We
      studied the patient by conventional arteriography, T1- and T2-weighted MRI and
      magnetic resonance angiography.

PMID- 8748909
TI  - Ageing--a biological perspective.

PMID- 8748917
TI  - Tubal surgery of IVF--making the best choice in the 1990s.
AB  - Although there are tubal causes of infertility for which surgery offers little or
      no chance of successful treatment, there are at least two situations
      sterilization reversal and microsurgical or laparoscopic adhesiolysis in the
      absence of fimbrial damage and/or male factor-in which subsequent live birth
      rates are excellent, 60-80% for the former and 45-65% for the latter. An
      advantage of tubal reconstruction over IVF-ET, which is the only viable
      alternative in tubal infertility, is avoidance of the risks of the stimulated
      ovulation protocol and multifetal gestation. Of course, the demands of
      microsurgery or operative laparoscopy are stringent; and the decision to
      undertake tubal reconstruction instead of IVF-ET must be coupled with appropriate
      patient selection.

PMID- 8748918
TI  - Primary therapy for tubal disease: surgery versus IVF.
AB  - Infertility involves fallopian tube occlusion or other malfunction in over 25% of
      cases. Reconstructive surgery offers the possibility of natural conception, but
      the success rate overall is less than 30% and if the hydrosalpinx is severe or
      other factors are involved, much lower than that. IVF-ET currently offers a much
      higher success rate. Although the cost of IVF per cycle is over three-fourths the
      total cost of tubal surgery, the eventual success rate of IVF is so much better
      than that of surgery that the costs per baby delivered are some 10% lower. In
      addition, more infertile couples are rewarded in their quest to have a child.

PMID- 8748919
TI  - The use of fibrin sealant in in vitro fertilization and embryo transfer.
AB  - OBJECTIVE: To evaluate the role of fibrin sealant for embryo transfer (ET) and
      the effect of patient mobilization after ET on pregnancy rates. DESIGN: A
      prospective, randomized, controlled study. METHODS: Two hundred eleven patients
      who were admitted to the IVF Unit over a period of 6 months participated in the
      study. Patients who had three or more embryos were randomly divided into two
      groups: group 1 (study group), in which ET was performed using fibrin sealant,
      and group 2, who served as the controls. Ovulation induction was carried out
      using the long GnRH-a suppression protocol. RESULTS: Comparison of the results
      regarding the implantation and pregnancy rates and ectopic pregnancy rate
      revealed a nonsignificant difference between the two groups. However, analysis of
      the results according to the patients' age revealed a significant increase in
      pregnancy (P < .05) and implantation (P < .01) rate in elderly patients (aged 39
      42) using fibrin sealant for ET as compared with controls. Furthermore, we found
      that bed rest has no advantage over patient mobilization after ET. CONCLUSION:
      The use of fibrin sealant for ET is advantageous in elderly women, but has no
      apparent effect on the success rate or ectopic pregnancy rate in younger
      patients. Immediate mobilization does not jeopardize the results of IVF-ET.

PMID- 8748920
TI  - Serum levels of follicle-stimulating hormone and luteinizing hormone after
      subcutaneous administration of human menopausal gonadotropin during pituitary
      suppression.
AB  - OBJECTIVE: The present study investigated the pharmacokinetics of a single
      subcutaneous dose of human menopausal gonadotropin (hMG) on serum follicle
      stimulating hormone (FSH) and luteinizing hormone (LH) concentrations. SUBJECTS
      AND METHODS: Six healthy female volunteers, aged 20-40 years, with regular
      menstrual cycles and normal endocrine profiles, who were not receiving any
      hormonal medication, were treated with the gonadotropin-releasing-hormone agonist
      buserelin to suppress endogenous gonadotropin release. One volunteer dropped out
      during treatment. When the serum estradiol concentration had fallen to below 500
      pmol/L, an injection of 150 IU hMG (HumegonR) was given subcutaneously.
      Immediately before injection and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 15, 20, 24, 48
      and 96 hours after, blood samples were drawn for determination of FSH and LH
      concentrations. RESULTS: The baseline FSH level was 2.8 IU/L, and peak
      concentration (6.8 IU/L) was reached 12 hours after hMG injection (median
      values). Exogenous LH could not be measured because of the presence of endogenous
      LH. DISCUSSION: The pattern of serum FSH concentrations after a single injection
      of hMG was found to resemble that seen after intramuscular hMG administration,
      although the peak FSH value was reached somewhat later.

PMID- 8748921
TI  - Induced midtrimester abortion and future fertility--where are we today?
AB  - OBJECTIVE: To review recent data and clinical opinions on the impact of induced
      midtrimester abortion on future fertility. DATA: MEDLINE search from 1971 to June
      1994. Studies on complications and sequelae of induced midtrimester abortion and
      impact upon future fertility were included. RESULTS: The possible complications
      that might be involved include uterine rupture, intrauterine adhesions, pelvic
      inflammatory disease, subsequent spontaneous abortions, cervical incompetence,
      subsequent premature labor, and ectopic pregnancy. Very little has been published
      on the effect of induced midtrimester abortion on future fertility, thus making a
      clear-cut conclusion difficult. CONCLUSIONS: As with first trimester abortion,
      midtrimester abortion seems to have no great effect on future fertility; and the
      rate of complications could be significantly reduced using appropriate measures,
      as discussed in the paper.

PMID- 8748922
TI  - Endometrial biopsy findings in infertility: analysis of 12,949 cases.
AB  - OBJECTIVE: Endometrial biopsy has been an important way of assessing infertile
      couples for several years. In this review of a wide-ranging series of endometrial
      biopsies of infertile couples in the Turkish population it was our aim to find
      the distribution of results according to the years 1956-1966, 1967-1980, 1981
      1992. SETTING: University hospital. SUBJECTS: 12,949 endometrial biopsies,
      referred to our gynecological pathology laboratory for infertility investigation
      between 1956 and 1992. METHOD: Patient report files from pathology laboratory
      data, analyzed retrospectively. The assessment of the biopsies is made by the
      same pathologist. RESULTS: 78.8% of cases had primary infertility, 21.2%
      secondary. Most of them were in the age group 26-35 years (48.8%). 37.58% of
      cases were found to show normal secretory endometrium, 20.95% proliferative
      endometrial changes, and 28.22% signs of luteal phase defect (LPD). Other local
      endometrial factors were also encountered, but in 1.79% the sample was considered
      insufficient for diagnosis. Moreover, in nine cases, malignancy was diagnosed
      with the help of endometrial biopsy. During the study period, cases of normal
      secretory endometrium and tuberculous endometritis were observed to decrease and
      LPD to increase significantly. It is worthy to note that in only 28 (0.21%) cases
      had endometrial biopsies been performed during a pregnancy cycle. CONCLUSION: We
      conclude that endometrial biopsy not only shows the hormonal response of
      endometrium but gives additional information about the local factors of
      endometrium concerning atrophy, specific and non-specific infections, and
      malignancy.

PMID- 8748923
TI  - The effect of varying inseminating sperm concentration in male factor and non
      male factor infertility during in vitro fertilization.
AB  - OBJECTIVE: To assess the effect of varying inseminating sperm concentrations on
      fertilization rates and polyspermy in human in vitro fertilization (IVF).
      SUBJECTS AND METHODS: Eighty-six couples who completed 107 consecutive IVF cycles
      were assigned to one of three groups according to the results of their semen
      analysis (SA), sperm penetration assay (SPA), and titers of antisperm antibodies
      (ASA). Group 1 (non-male factor) had normal results for SA, SPA and ASA; group 2
      had one abnormal result; and group 3 had two or more abnormal results.
      Inseminating concentrations of 50,000, 250,000, or 500,000 progressively motile
      sperm/oocyte were prospectively assigned to groups 1, 2 and 3, respectively. MAIN
      OUTCOME MEASURES: Incidence of polyspermy and fertilization rates. RESULTS: A
      total of 992 oocytes were available for analysis. The fertilization rate of 61%
      for non-male factor patient (group 1) was significantly higher than for male
      factor patients [group 2 (48%) and group 3 (43%; P < .01)]. The incidence of
      polyspermy was 3.3%, 5.5%, and 0% for groups 1, 2 and 3, respectively, and did
      not differ significantly between the non-male factor and male factor groups (P =
      .16). Polyspermic fertilization was increased in both mature (4.1%) and
      postmature (5.7%) as compared to immature oocytes (1.4%; P < .05). CONCLUSION: In
      male factor infertile couples, increasing the inseminating concentration to
      250,000 or 500,000 motile sperm/oocyte does not result in an increase in the
      incidence of polyspermy but does not improve fertilization rates.

PMID- 8748924
TI  - Inhibition of proteolysis enhances aluminum-induced perikaryal neurofilament
      accumulation but does not enhance tau accumulation.
AB  - As observed for neurons in situ, phosphorylated neurofilament (NF) epitopes are
      normally segregated within the axonal cytoskeleton of NB2a/d1 cells. However,
      accumulations of phosphorylated NFs develop in NB2a/d1 perikarya following
      exposure to aluminum salts and following inhibition of proteolysis. In the
      present study, we observed that perikarya of cells exposed to both aluminum and
      the protease inhibitor C1 (also known as "AllNal") were more intensely labeled by
      monoclonal antibodies directed against both nonphosphorylated and phosphorylated
      epitopes than were cells treated with either aluminum or protease inhibitor
      alone. Since these monoclonal antibodies crossreact with tau, we also
      immunostained cells treated under these conditions with monoclonal antibodies
      directed against phosphate-insensitive (5E2) and phosphorylated (PHF-1) epitopes
      of tau. Aluminum treatment, but not C1 treatment, induced accumulation of total
      tau isoforms as judged by an increase in 5E2 immunoreactivity. Neither treatment,
      either separately or in combination, induced an increase in PHF-1
      immunoreactivity. These findings suggest that alterations in immunoreactivity
      with SMI antibodies reflected increases in NF epitopes. This was confirmed by
      immunoblot analyses. Since proteolysis is apparently instrumental in maintaining
      the normal distribution patterns of phosphorylated NF epitopes, these findings
      implicate deficiencies in proteolytic mechanisms in the development of
      neurofibrillary pathology, and underscore the possibility of a multiple etiology
      in human neuropathological conditions.

PMID- 8748925
TI  - Time course of ICAM-1 expression and leukocyte subset infiltration in rat
      forebrain ischemia.
AB  - The time course of ICAM-1 expression and leukocyte subset infiltration was
      studied in a model of CNS reperfusion injury in adult rats. Leukocyte adhesion
      and infiltration, mediated in part by intercellular adhesion molecule-1 (ICAM-1),
      appears to potentiate CNS reperfusion injury. The timing and relationship between
      ICAM-1 staining and leukocyte infiltration postglobal CNS ischemia is unknown.
      Reversible forebrain ischemia was produced in 32 adult Sprague-Dawley rats using
      the two-vessel occlusion model with histologic analysis performed at specific
      intervals postischemia: 1, 3, 6, 12, and 24 h, 4 and 7 d, or sham-operated
      controls (n = 4 each group). Monoclonal antibodies against ICAM-1 (1A29 and TM8),
      a specific granulocyte (PMN) (HIS48), and a specific monocyte/macrophage (M phi)
      (ED1) were used. No specific leukocyte and only rare ICAM-1 vessel
      immunoreactivity was observed in sham controls. ICAM-1: Significant expression in
      microvessels beginning at 1 h with additional diffuse CA1 pyramidal layer
      staining beginning at 4 d. Leukocytes: No PMN cells and rare M phi identified at
      6 and 12 h. By 24 h: moderate infiltrate in areas of ICAM-1 expression of PMN and
      M phi. At 4 and 7 d: only M phi accumulation, cellular morphology now similar to
      microglia. The results of this study indicate that early and persistent ICAM-1
      expression occurs following CNS ischemia with associated leukocyte infiltration.

PMID- 8748926
TI  - Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration
      in Alzheimer disease?
AB  - Cerebrospinal fluid (CSF) biochemical markers for Alzheimer disease (AD) would be
      of great value to improve the clinical diagnostic accuracy of the disorder. As
      abnormally phosphorylated forms of the microtubule-associated protein tau have
      been consistently found in the brains of AD patients, and since tau can be
      detected in CSF, two assays based on several well-defined monoclonal tau
      antibodies were used to study these proteins in CSF. One assay detects most
      normal and abnormal forms of tau (CSF-tau), while the other is highly specific
      for phosphorylated tau (CSF-PHFtau). A marked increase in CSF-PHFtau was found in
      AD (2230 +/- 930 pg/mL), as compared with controls (640 +/- 230 pg/mL; p <
      0.0001), vascular dementia, VAD (1610 +/- 840 pg/mL; p < 0.05), frontal lobe
      dementia, FLD (1530 +/- 1000 pg/mL; p < 0.05), Parkinson disease, PD (720 +/- 590
      pg/mL; p < 0.0001), and patients with major depression (230 +/- 130 pg/mL; p <
      0.0001). Parallel results were obtained for CSF-tau. No less than 35/40 (88%) of
      AD patients had a CSF-PHFtau value higher than the cutoff level of 1140 pg/mL in
      controls. The present study demonstrates that elevated tau/PHFtau levels are
      consistently found in CSF of AD patients. However, a considerable overlap is
      still present with other forms of dementia, both VAD and FLD. CSF-tau and CSF
      PHFtau may therefore be useful as a positive biochemical marker, to discriminate
      AD from normal aging, PD, and depressive pseudodementia. Further studies are
      needed to clarify the sensitivity and specificity of these assays, including
      follow-up studies with neuropathological examinations.

PMID- 8748927
TI  - cAMP-dependent protein kinase in cerebral microvessels in aging and Alzheimer
      disease.
AB  - The purpose of this study was to compare the effects of aging and Alzheimer
      disease (AD) on the important intracellular signaling enzyme cAMP-dependent
      protein kinase A (PKA) in cerebral microvessels. PKA activity and levels were
      measured in microvessels isolated from the brains of adult and aged rodents as
      well as from the cerebral cortices of AD and elderly control patients. The
      results showed that cerebral microvessels from aged rats have significantly (p <
      0.01) higher PKA activity and levels when compared to cerebral microvessels from
      adult rats. In contrast, no significant difference was found between PKA activity
      or levels in cerebral microvessels from AD patients when compared to controls.
      These results indicate that in cerebral microvessels both PKA activity and levels
      increase with age but are unaffected by AD. The data suggest that protein
      phosphorylation in brain microvessels may be affected differentially by aging and
      dementia.

PMID- 8748928
TI  - Regulation of protein kinase C activity in cerebral microvessels.
AB  - Regulation of protein kinase C (PKC)-mediated responses may occur by inhibition
      of PKC-dependent phosphorylation or by dephosphorylation of targets by specific
      phosphatases. Mechanisms for the regulation of PKC were examined in isolated
      cerebral microvessels and compared to those in brain. The data demonstrated that
      inhibitors of phosphorylation are responsible for the regulation in brain
      microvessels while dephosphorylation by protein phosphatases accounts for a
      substantial portion of the regulation of the PKC response in brain. In addition,
      the inhibitory activity apparently increases with age. These results suggest that
      the control of PKC may be cell-type specific and developmentally regulated.

PMID- 8748929
TI  - Striatal dopamine depletion, tremors, and hypokinesia following the intracranial
      injection of S-adenosylmethionine: a possible role of hypermethylation in
      parkinsonism.
AB  - The major symptoms of Parkinson disease (PD) are tremors, hypokinesia, rigidity,
      and abnormal posture, caused by the degeneration of dopamine (DA) neurons in the
      substantia nigra (SN) and deficiency of DA in the neostriatal DA terminals.
      Norepinephrine (NE) and serotonin (5-HT) levels in the neostriatum and tyrosine
      hydroxylase and melanin pigments in the substantia nigra are also decreased, and
      brain cholinergic activity is increased. The cause of PD is unknown, but PD is an
      age-related disorder, suggesting that changes that occur during the aging process
      may help to precipitate PD. Methylation increases in aging animals. Increased
      methylation can deplete DA, NE, and 5-HT; increase acetylcholine; and cause
      hypokinesia and tremors. These effects are similar to changes seen in PD, and
      interestingly also, they are similar to some of the changes that are associated
      with the aging process. It is suggested, therefore, that increased methylation
      may be an inducing factor in parkinsonism. Accordingly, the effects of an
      increase in methylation in the brain of rats were studied. S-adenosylmethionine
      (AdoMet), the limiting factor in the methylation process, was injected into the
      lateral ventricle of rats. Specific behavioral changes that resemble changes seen
      in PD were investigated. The results showed that AdoMet caused tremors, rigidity,
      hypokinesia, and depleted DA. The hypokinetic effects of a single dose of AdoMet
      lasted for about 90 min. AdoMet has a dose-dependent hypokinetic effect. A dose
      of 9.4 nmol reduced movement time (MT) by 68.9% and increased rest time (RT) by
      20.7%, and a dose of 400 nmol reduced MT by 92.4% and increased RT by 27.6%. The
      normethyl analog of AdoMet, S-adenosylhomocysteine, did not cause hypokinesia or
      tremors, but it blocked the AdoMet-induced motor effects. L-dopa, the precursor
      of DA, also blocked the AdoMet-induced motor effects. These data suggest that the
      methyl group of AdoMet as well as DA depletion are involved in the AdoMet-induced
      motor effects. A dose of 0.65 mumol of AdoMet depleted DA in the ipsilateral
      caudate nucleus (CN) or neostriatum by 50.1%, and DA in the contralateral CN was
      reduced by 9.3%. Double the dose of AdoMet did not increase the depletion of DA
      on the ipsilateral CN, but DA in the contralateral CN was decreased by 26.3%.
      Taken together, the results suggest that increased methylation may contribute to
      the symptoms of PD.

PMID- 8748930
TI  - Motor alterations and neuronal damage induced by intracerebral administration of
      Ruthenium red: effect of NMDA receptor antagonists and other anticonvulsant
      drugs.
AB  - The effects of the intracerebroventricular (icv) and the intrahippocampal (ih)
      microinjection of the inorganic dye Ruthenium red (RuR) on motor activity, and
      the protective action of excitatory amino acid receptor antagonists and of
      GABAergic drugs, were studied in the rat. When administered icv, RuR produced
      intense tonic-clonic convulsions which were refractory to N-methyl-D-aspartate
      (NMDA) receptor antagonists and to diphenylhydantoin, whereas aminooxyacetic acid
      (AOA) and valproate only partially protected against seizure activity. The most
      notable motor effect of the ih RuR administration was the appearance of intense
      wet-dog shakes (WDS) behavior, which was remarkably attenuated by the icv or
      intraperitoneal (ip) administration of the NMDA receptor antagonists (+/-)-3-(2
      carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), CGP-37849, and MK-801, but
      not by their ih coinjection with RuR. Systemic AOA and valproate were also
      effective in reducing the number of WDS, whereas the non-NMDA receptor antagonist
      CNQX was ineffective. Light and electron microscopic observations of the RuR
      injected brains revealed that the dye was highly concentrated in neuronal somas
      located in or near the injected areas. In the case of the CA1 region, remarkable
      damage of the pyramidal neurons was manifested by vacuolization, and 5-9 d after
      the injection notable cell loss and disruption of the CA1 cell layer organization
      was apparent. The results indicate that RuR penetrates selectively neuronal
      bodies and damage them, and suggest that the resulting motor alterations involve
      hyperactivity of glutamatergic neurotransmission.

PMID- 8748931
TI  - Phase II enzymes and bioactivation.
AB  - A colloquium entitled Phase II enzymes and bioactivation was held during the 10th
      International Symposium on Microsomes and Drug Oxidations in Toronto, Ont., on
      July 20, 1994. This colloquium was a tribute in recognition of the contributions
      by Dr. James R. Gillette in advancing our understanding of drug metabolism and
      chemical toxicity. A major focus of the colloquium was formation of conjugates
      such as those with glutathione (GSH) that may not lead to detoxification but to
      bioactivation. The GSH conjugates may be further metabolized to reactive species
      that cause toxicity. The nephrotoxicity of hydroquinone and bromobenzene is
      mediated via quinone - glutathione conjugates, and is manifested in cellular
      changes, including induction of the gadd-153 and hsp-70 mRNA. The formation of
      GSH conjugates is also involved in the bioactivation of the vicinal dihalopropane
      1,2-dibromo-3-chloropropane; cytotoxic lesions are observed in the kidney and
      testes The evidence indicates that conjugation is mediated by the GSH S
      transferases. The symposium also covered aspects of the importance of conjugation
      in the pharmacokinetics of certain drugs. Conjugation reactions including
      sulfation are markedly influenced by the manner in which the liver processes the
      drug. Characteristics such as erythrocyte binding, as in the case of
      acetaminophen, become limiting factors in the conjugation reactions. Conjugation
      reactions can lead to a different outcome, such as acquired drug resistance.
      Conjugation of metallothioneins with the alkylating mustard drugs melphalan and
      chlorambucil can lead to the formation of protein adducts. Conjugation of
      reactive intermediates with these small molecular weight proteins may be
      considered as a phase II reaction and a mechanism of detoxification. A different
      pathway for the metabolism of xenobiotics is catalyzed by the carboxylesterases,
      a family of enzymes that is involved in hydrolysis of chemical compounds,
      generally leading to detoxification. Three rat esterases have been purified,
      cloned, and characterized. Two forms, hydrolase A and hydrolase B, are present in
      liver microsomes in a number of species, including the human. These are also
      detected in extrahepatic tissues. A third esterase, hydrolase S, is found in rat
      liver microsomes and rat serum, and may be a serum carboxylesterase secreted from
      the liver. A better knowledge of esterases will advance our understanding of
      pharmacokinetics and mechanisms of the effects of chemicals such as phenacetin
      and acetaminophen, two drugs that Dr. Gillette has worked with extensively. The
      data presented herein reflect the new and innovative approaches that have been
      adopted to investigate various aspects of chemical toxicity and drug metabolism.
      These data also indicate that significant insights are likely to come from
      integrated approaches utilizing established toxicological techniques together
      with those from other disciplines, including molecular biology and analytical
      chemistry.

PMID- 8748932
TI  - beta-cell stimulus - secretion coupling defects in rodent models of obesity.
AB  - Hyperinsulinemia accompanies obesity in human patients and experimental rodent
      models and exacerbates insulin resistance, but the causes of increased insulin
      secretion remain obscure. This review examines progress in defining biochemical
      and molecular beta-cell defects that have elucidated in the past 5 years. Some
      defects, such as decreased glucose transport, decreased mitochondrial FAD-linked
      glycerophosphate dehydrogenase activity, and altered anomeric specificity for
      glucose, become evident only after onset of non-insulin-dependent diabetes
      mellitus. Thus, these defects are unlikely to play a role in the pathogenesis of
      hyperinsulinemia in obesity. Other biochemical changes, including increased
      glucokinase and (or) hexokinase function, increased glucose cycling, and altered
      regulation of intracellular Ca2+ are present in obese nondiabetic animals and may
      therefore contribute to development of hyperinsulinemia. Few developmental
      studies have been performed to correlate onset of defects with environmentally
      and genetically mediated control mechanisms of beta-cell function. However, the
      availability of new molecular biology techniques should facilitate identification
      of factors causing hyperinsulinemia in obesity.

PMID- 8748933
TI  - Antihypertensive effect of corilagin in the rat.
AB  - The antihypertensive effect of corilagin, one of the ellagitannins purified from
      the seeds of Euphoria longana Lam. (Sapindaceae), was investigated in the
      spontaneously hypertensive rat (SHR). Administration of corilagin into conscious
      SHR at 5 mg/kg produced an antihypertensive effect equivalent to that induced by
      1 mg/kg of guanethidine. This dose-dependent hypotensive effect was comparable
      with that observed in anesthetized SHR animals. Corilagin did not modify the
      baroreflex sensitivity in phenylephrine-challenged SHR. Corilagin reduced plasma
      noradrenaline in a dose-dependent fashion, an effect that was maintained in
      adrenalectomized rats. Failure of the antagonists for alpha2-adrenoceptors,
      idazoxan and yohimbine, as well as for dopamine receptors, haloperidol and
      domperidone, to reverse the antihypertensive actions of corilagin ruled out the
      participation of these receptors. Moreover, corilagin attenuated the pressor
      effects of methoxamine and Bay K8644 to a similar degree, indicating the direct
      effect of corilagin on vascular activity in rats. These results suggest that
      corilagin possesses the ability to lower blood pressure through the reduction of
      noradrenaline release and (or) direct vasorelaxation.

PMID- 8748934
TI  - Age-related changes in electrophysiological responses to muscarinic receptor
      stimulation in rat myocardium.
AB  - Recent studies have demonstrated that the negative chronotropic and inotropic
      responses of the heart to cholinergic muscarinic receptor stimulation are
      strikingly enhanced with aging in the rat model. The present study investigated
      the electrophysiological basis of this phenomenon by determining the effects of a
      muscarinic receptor agonist, carbachol, on transmembrane action potential
      parameters in right atrial tissue and right ventricular free wall preparations
      from adult (6-8 months old) and aged (26-28 months old) Fischer 344 rats. In
      addition, the effect of carbachol on atrioventricular conduction time (AVT) was
      determined in isolated perfused beating hearts. The results showed the following.
      The baseline maximum diastolic potential (MDP: adult, -76.4 +/- 1.8 mV; aged, 
      66.8 +/- 1.5 mV; p < 0.05; n = 5) but not the action potential duration measured
      at 95% repolarization (APD95: adult, 40.0 +/- 5.0 ms; aged, 47.4 +/- 6.7 ms; n =
      5) differed significantly in aged compared with adult atrium. No significant age
      related difference was evident in baseline MDP measured in ventricular epicardium
      (adult, -69.8 +/- 0.5 mV; aged, -69.0 +/- 1.1 mV; n = 6) or endocardium (adult, 
      72.5 +/- 1.4 mV; aged, -73.0 +/- 1.2 mV; n =6). The baseline action potential
      duration measured at 50% repolarization (APD50) differed significantly with age
      in ventricular endocardium (adult, 11.6 +/- 2.2 ms; aged, 23.0 +/- 4.6 ms; p <
      0.05; n =6) but not in epicardium (APD50: adult, 8.1 +/- 0.4 ms; aged, 13.0 +/-
      2.3 ms; n = 6). Superfusion with carbachol (0.1 nM - 10 mu M) resulted in
      concentration-dependent hyperpolarization of MDP in atrium; the magnitude of
      hyperpolarization differed significantly with age (2.5-fold higher in the aged; p
      < 0.05; n = 5). Carbachol caused concentration-dependent shortening of APD50;
      this effect differed significantly with age in the ventricle (2-fold greater in
      the aged; p < 0.05; n = 6) but not in the atrium. Carbachol prolonged the AVT in
      atrial-paced (240 beats/min) hearts; the magnitude of carbachol-induced increase
      in AVT did not differ significantly with age. These results are consistent with
      the possibility that in the aging heart, greater hyperpolarization at the level
      of the right atrium (likely involving pacemaker cells) and greater shortening of
      APD50 at the level of ventricular myocytes may contribute to the enhanced
      cholinergic-triggered bradycardia and negative inotropic response, respectively.

PMID- 8748935
TI  - Age of rat influences isolation of jejunal enterocytes from along the villus.
AB  - Aging is associated with alterations in the functions of the intestine. Also, the
      functions of the intestine vary along the length of the villus. A method is
      reported for the isolation of four fractions of enterocytes from along the villus
      of young (3 months, 300-350 g) and old (8 months, 700-750 g) male Wistar rats.
      Different qualitative patterns are seen when the activities of alkaline
      phosphatase (AP), invertase (INV), or [3H]methylthymidine incorporation are
      expressed on the basis of millimoles per gram protein, percentage of highest
      activity, percentage of total activity, cumulative activity for each fraction, or
      millimoles per gram protein versus cumulative percentage of total protein. When
      expressed on the basis of protein, AP is higher in upper (FI) versus lower (FIV)
      villus fractions, and in each fraction AP is higher in old versus young animals.
      INV varies little along the villus or between young and old rats;
      [3H]methylthymidine incorporation is highest in the crypt cells. The ratio mg
      protein/mg DNA varies along the villus and is twofold higher in young than in old
      rats. In contrast, when activities are expressed on the basis of DNA, the same
      qualitative patterns are seen along the villus, but INV and AP are both higher in
      young than in old rats. In summary (i) the qualitative and quantitative
      differences in the activities of AP and INV along the villus of old versus young
      rats vary when the data are expressed on the basis of DNA rather than protein;
      (ii) the ratio of protein to DNA varies along the villus in young and old
      animals, and for this reason it is appropriate to report enzyme activity on the
      basis of enterocyte DNA; and (iii) INV and AP, when expressed on the basis of
      DNA, are higher in young than in old animals. Thus, the isolation of rat jejunal
      enterocytes from along the villus is affected by the age of the animals.

PMID- 8748936
TI  - Massive intestinal resection depresses circular smooth muscle contractility in
      the rat.
AB  - To determine whether functional changes in in vitro contractility and in vivo
      gastrointestinal transit accompany the adaptive structural changes seen in
      jejunal circular muscle after massive intestinal resection, rats were subjected
      to either surgical resection of 75% of the mid-jejunoileum or a sham operation.
      Basal stress in response to stretch was similar for both groups on postoperative
      days 10, 20, 30, and 40. By day 10 after surgery, tissues from resected rats
      exhibited a significant reduction in bethanechol-stimulated tonic stress and in
      frequency of phasic contractions. The amplitude of spontaneous phasic activity
      was significantly increased; however, following cholinergic stimulation, the
      magnitude of the increase in the amplitude of phasic activity was significantly
      reduced. Experiments with tetrodotoxin (10(-6) M) indicated a myogenic origin to
      the reduction in bethanechol-stimulated tonic stress and the reduced frequency
      and altered amplitude of phasic contractile activity in resected animals. The
      tonic stress developed in response to depolarization with KCl did not differ
      significantly between sham-operated and resected rats. Transit studies showed no
      change in the rate of gastric emptying after resection but did reveal a
      significant reduction in the velocity of intestinal transit. Thus, following
      massive intestinal resection the bethanechol-stimulated tonic stress response and
      phasic contractile activity of circular smooth muscle are significantly reduced,
      concomitant with altered intestinal transit. The reduction in contractility in
      the resected animals may be due to an alteration at the level of the smooth
      muscle receptor and (or) its signal transduction pathway.

PMID- 8748937
TI  - Effects of uridine triphosphate on skinned skeletal muscle fibers of the rat.
AB  - Chemically skinned muscle fibers from rat extensor digitorum longus muscle were
      used to study the effects of uridine triphosphate (UTP) on Ca2+ uptake and
      release by the sarcoplasmic reticulum (SR) and on Ca2+-activated tensions. Total
      replacement (2.5 mM) of adenosine triphosphate (ATP) with UTP (i) increased
      submaximal Ca2+-induced tension (pCa 6.2-5.8) but diminished Po, the maximum
      tension elicited by pCa 4.2, by ca. 15%, (ii) markedly reduced Ca2+ uptake by the
      SR (evaluated by caffeine-elicited tension); and (iii) induced tension in Ca2+
      loaded fibers. The UTP-induced tension averaged 55% of Po and its rates of
      development and decay were considerably slower than those of caffeine-evoked
      tension. The UTP-induced tension (i) depended on the Ca2+-loading conditions;
      (ii) was reversibly blocked by brief (15 s) exposures of Ca2+-loaded fibers to 5
      mM EGTA or by pretreatment with caffeine; (iii) was abolished by functional
      disruption of the SR with the nonionic detergent Brij-58; and (iv) persisted
      after blockade of the SR Ca2+ release channels with ruthenium red. Exposure of
      Ca2+-loaded fibers to UTP depressed the tension elicited subsequently by
      caffeine, and enhanced the rate of depletion of caffeine-sensitive Ca2+ stores
      during soaking in relaxing solutions containing 5 mM EGTA. The UTP-induced
      tension is attributed to increased release of Ca2+ from the SR, via a ruthenium
      red insensitive pathway(s), combined with reduced Ca2+ uptake by the SR and
      increased Ca2+ affinity of the contractile proteins.

PMID- 8748938
TI  - Dissociation of thermogenic and trophic actions of norepinephrine in brown
      adipocytes of Richardson ground squirrels.
AB  - Richardson ground squirrels are hibernators with seasonal changes in the
      thermogenic capacity of brown adipose tissue (BAT). The objective of this work
      was to evaluate whether norepinephrine (NE) acts both as a thermogenic and a
      growth factor in BAT. Brown adipocytes were isolated by collagenase digestion of
      axillary BAT and kept in a tissue culture incubator in methionine-free Dulbecco's
      modified Eagle's medium supplemented with albumin, antibiotics, and calf serum
      with or without NE for up to 24 h. For short-term incubations (<6 h), calf serum
      was omitted. Freshly isolated brown adipocytes responded to NE with 10- to 20
      fold increases in rates of oxygen uptake. This ability to respond calorigenically
      to NE was maintained over a 24-h period. However, no significant increase in
      [35S]methionine incorporation into cellular proteins was observed when brown
      adipocytes were incubated for 1-6 or 24 h with NE. When labeled cell proteins
      were separated by SDS-PAGE and visualized by autoradiography, no selective change
      in protein labeling, particularly in the uncoupling protein (32 kDa) region was
      observed. Likewise, [35S]methionine incorporation into immunoprecipitable
      uncoupling protein was not affected by the presence of NE. These results suggest
      a dissociation between the thermogenic and growth effects of NE in BAT of
      Richardson ground squirrels.

PMID- 8748939
TI  - Pyrogen - prostaglandin coupling in the pathogenesis of fever: evidence against a
      role for nitric oxide.
AB  - There is much debate on the mechanism by which blood-borne pyrogens trigger
      prostaglandin E2 (PGE2) synthesis in brain and fever. This investigation was
      undertaken to determine whether nitric oxide qualifies as a signal transducer for
      pyrogens at the interface between blood and brain. Experiments were carried out
      in vitro and in vivo using, respectively, preparations of cerebral tissue and
      microvessels from the rat, and the conscious, chronically instrumented cat. In
      vitro preparations produced PGE2 and its production increased during a 30-min
      treatment with interleukin 1 (brain tissue) or endotoxin (microvessels). In
      addition, both pyrogens increased cyclic GMP levels in cerebral microvessels. In
      both brain tissue and microvessels, NG-nitro-L-arginine had no effect on basal
      PGE2 release, while it curtailed the pyrogen-stimulated release. The same
      treatment reduced the cyclic GMP accumulation brought about by pyrogens in the
      microvessels. Conversely, in the conscious cat, inhibitors of nitric oxide
      synthesis (NG-monomethyl-L-arginine, NG-nitro-L-arginine) had no effect on fever
      and the concomitant elevation of PGE2 in cerebrospinal fluid, regardless of the
      pyrogen used (endotoxin, interleukin 1) and the route of administration
      (intravenous, intracerebroventricular). We conclude that nitric oxide may serve
      as a pyrogen mediator in brain. This mediator function, however, is seemingly not
      important in the development of fever.

PMID- 8748940
TI  - Developmental change in fast Na channel properties in embryonic chick ventricular
      heart cells.
AB  - To assess development changes in kinetic properties of the cardiac sodium
      current, whole-cell voltage-clamp experiments were conducted using 3-, 10-, and
      17-day-old embryonic chick ventricular heart cells. Experimental data were
      quantified according to the Hodgkin-Huxley model. While the Na current density,
      as examined by the maximal conductance, drastically increased (six- to seven
      fold) with development, other current - voltage parameters remained unchanged.
      Whereas the activation time constant and the steady-state activation
      characteristics were comparable among the three age groups, the voltage
      dependence of the inactivation time constant and the steady-state inactivation
      underwent a shift in the voltage dependence toward negative potentials during
      embryonic development. Consequently, the steady-state (window current)
      conductance, which was sufficient to induce automatic activity in the young
      embryos, was progressively reduced with age.

PMID- 8748941
TI  - Baclofen attenuates cardiorespiratory effects of vagal C fiber stimulation in
      rats.
AB  - We tested the hypothesis that gamma-aminobutyric acid (GABA) acting on GABA B
      receptors modulates vagal C fiber mediated reflexes. The effects of a GABA B
      receptor agonist, (-)-baclofen, injected bilaterally into the nucleus tractus
      solitarius (NTS), on the cardiorespiratory response to C fiber stimulation with
      phenyldiguanide (PDG) introduced into the right atrium were evaluated in urethane
      anesthetized Wistar rats. We recorded integrated diaphragmatic EMG (Di) and mean
      arterial blood pressure (ABP). Before injections of baclofen into the NTS, PDG
      caused bradycardia, hypotension, and apnea, followed by a decrease in Di
      amplitude and variable changes in respiratory timing. Only injections of baclofen
      at 0.6 mm caudal to the obex reduced or prevented the PDG-evoked apnea. In
      contrast, independent of site of injection baclofen diminished bradycardia and
      the decrease in Di in postapnea breaths. The ABP response to PDG was never
      affected by baclofen. A GABA B receptor antagonist, CGP 35348, fully restored the
      responses to PDG, but CGP 35348 alone did not affect the responses to PDG. Our
      results suggest that GABA B receptors are present on neurons in the medullary
      pathway of vagal C fibers. In the caudal NTS, GABA B receptors modulate the PDG
      evoked apnea, and within the larger area of the NTS these receptors modulate
      bradycardia and postapnea patterns of breathing. The absence of effects of CGP
      35348 alone implies that GABA B receptors on the vagal C fiber pathway are not
      tonically active in rats.

PMID- 8748942
TI  - Suppression of sympathetic nervous system is involved in hypotension and
      bradycardia during hemofiltration in anesthetized dogs.
AB  - Hypotension occurring during hemodialysis is often accompanied by paradoxical
      bradycardia. However, the mechanism is poorly understood. This study was designed
      to determine the role of the sympathetic nervous system in hemodialysis-induced
      hypotension and bradycardia. We measured efferent sympathetic nerve activities to
      the heart (CNA), kidney (RNA), liver (HNA), spleen (SpNA), and adrenal gland
      (AdNA), along with heart rate (HR), blood pressure (BP), central venous pressure
      (CVP), and left atrial pressure (LAP) during hemofiltration performed at a rate
      of 0.3 mL .center dot Kg(-1) center dot min(-1) for 30 min in anesthetized dogs.
      The response to hemorrhage was also studied at the same bleeding speed.
      Hemorrhage caused a decrease in BP (-18 +/- 1 mmHg; 1 mmHg = 133.3 Pa) with
      reflex increases in HR (7 +/- 2 beats/min) and sympathetic nerve activities. In
      contrast, hemofiltration caused a decrease in CNA (85 +/- 18%), HNA (86 +/- 11%),
      and SpNA (88 +/- 11%) with greater decreases in BP (-43 +/- 10 mmHg) and HR (-27
      +/- 14 beats/min) than hemorrhage. During hemofiltration, the decreases in BP,
      HR, CNA, HNA, and SpNA were attenuated after vagotomy. Hematocrit increased by
      6.5% at 30 min after hemofiltration, whereas it decreased by 4.3% after
      hemorrhage. These results suggest that hemofiltration suppresses the sympathetic
      nervous system, resulting in decreases in HR and BP. Furthermore, this
      sympathetic suppression during hemofiltration is mediated by vagal afferents.

PMID- 8748943
TI  - Generation of slow wave type action potentials in the mouse small intestine
      involves a non-L-type calcium channel.
AB  - Intrinsic electrical activities in various isolated segments of the mouse small
      intestine were recorded (i) to characterize action potential generation and (ii)
      to obtain a profile on the ion channels involved in initiating the slow wave type
      action potentials (slow waves). Gradients in slow wave frequency, resting
      membrane potential, and occurrence of spiking activity were found, with the
      proximal intestine exhibiting the highest frequency, the most hyperpolarized cell
      membrane, and the greatest occurrence of spikes. The slow waves were only
      partially sensitive to L-type calcium channel blockers. Nifedipine, verapamil,
      and pinaverium bromide abolished spikes that occurred on the plateau phase of the
      slow waves in all tissues. The activity that remained in the presence of L-type
      calcium channel blockers, the upstroke potential, retained a similar amplitude to
      the original slow wave and was of identical frequency. The upstroke potential was
      not sensitive to a reduction in extracellular chloride or to the sodium channel
      blockers tetrodotoxin and mexiletine. Abolishment of the Na+ gradient by removal
      of 120 mM extracellular Na+ reduced the upstroke potential frequency by 13 - 18%
      and its amplitude by 50 - 70% in the ileum. The amplitude was similarly reduced
      by Ni2+ (up to 5 mM), and by flufenamic acid (100 mu M), a nonspecific cation and
      chloride channel blocker. Gadolinium, a nonspecific blocker of cation and stretch
      activated channels, had no effect. Throughout these pharmacological
      manipulations, a robust oscillation remained at 5 - 10 mV. This oscillation
      likely reflects pacemaker activity. It was rapidly abolished by removal of
      extracellular calcium but not affected by L-type calcium channel blockers. In
      summary, the mouse small intestine has been established as a model for research
      into slow wave generation and electrical pacemaker activity. The upstroke part of
      the slow wave has two components, the pacemaker component involves a non-L-type
      calcium channel.

PMID- 8748944
TI  - Comparative studies on differential inhibition of the renin - angiotensin system
      in the anesthetized guinea pig.
AB  - The present study compares the hemodynamic effects and mechanisms of action of
      angiotensin II (AngII) antagonists, angiotensin converting enzyme (ACE)
      inhibitors, and renin inhibitors in the guinea pig, an animal with high
      similarity to primates in terms of in vitro and in vivo responses to several
      human renin inhibitors. Animals were anesthetized with urethane and ketamine. The
      carotid artery was catheterized for monitoring blood pressure and heart rate.
      After 30 min stabilization, drug (or vehicle) effects were monitored for 1 h
      following each increasing dose (i.v. bolus injection). Drugs tested include
      losartan, an AngII receptor antagonist; two renin inhibitors, BILA 2157 BS and PD
      134672; and captopril, an ACE inhibitor. All drugs dose dependently decreased
      blood pressure. Diastolic blood pressure was reduced more than systolic blood
      pressure, suggestive of vasodilation. The maximum decrease (32 +/- 6%, p < 0.05
      vs. vehicle) in mean arterial blood pressure (MABP) by losartan was achieved with
      a dose of 1 mg/kg. A similar decrease in MABP was observed with renin inhibitors
      at a dose of 3 mg/kg, without affecting heart rate. A further increase in the
      dose of renin inhibitors (6 mg/kg) decreased not only blood pressure but also
      heart rate. Captopril decreased MABP with a maximum of 48 +/- 3% (p < 0.05 vs.
      vehicle, losartan, and PD-134672). In the presence of HOE-140, a bradykinin
      antagonist, the MABP decrease by captopril was only 35 +/- 4%, (p < 0.05 vs.
      captopril alone). Bilateral nephrectomy reduced the peak MABP effect of PD-134672
      by 67%, while the effects of captopril on MABP were affected to a lesser degree
      (57%). Therefore, captopril remains more effective in reducing MABP (p < 0.05 vs.
      that of PD-134672). These results suggest that renin inhibitors and AngII
      antagonists act more specifically on the renin - angiotensin system cascade,
      while captopril acts partially by a bradykinin-dependent mechanism. The small
      animal model described provides a novel tool for the comparative pharmacologic
      assessment of different renin - angiotensin system inhibitors.

PMID- 8748945
TI  - Diurnal variation of intensive running in food-deprived rats.
AB  - Manipulation of the food supply can induce either intense hyperactive wheel
      running or a fatal activity anorexia in rats that is strongly analogous to that
      seen in humans. The abnormal behaviour is accompanied by alterations in the
      diurnal pattern of activity. As part of a detailed study of hyperactivity and
      anorexia, spontaneous wheel running by male rats was studied under three
      conditions: ad libitum feeding; restriction to 15 g of food per day; and
      restriction to a single 90-min meal per day. Ad libitum fed rats increased their
      running at the rate of 440 +/- 60 m/day per day, stabilizing after day 10 at 6045
      +/- 3010 m/day. The running occurred in short bursts throughout the dark period
      and at the beginning of the light period. Rats restricted to 15 g/day increased
      their running at the significantly greater (p < 0.001) rate of 1230 +/- 120 m/day
      per day, reaching 12 200 +/- 4 090 m/day by day 10 and thereafter stabilizing at
      13 600 +/- 4 160 m/day. The running was initially triphasic and confined to the
      dark period but eventually progressed to a biphasic pattern. The rats restricted
      to a single 90-min access period to food each day showed an even greater rate of
      increase in running, attaining 1930 +/- 288 m/day per day (p < 0.02 vs. 15 g/day
      group). These animals decreased eating and decompensated by day 4. The diurnal
      pattern of activity was disturbed from day 1 of the protocol, and by day 4 the
      rats ran essentially continuously throughout the daily cycle. The sensitivity to
      hyperactivity is a function of the severity of food restriction in this animal
      model of hyperactivity. It is paralleled by a marked disturbance of the diurnal
      pattern of activity, suggesting that the hyperactivity is related to a basic
      central nervous system dysfunction.

PMID- 8748946
TI  - Microvascular architecture and exchange in synovial joints.
AB  - The microcirculation of the synovial lining of joints displays many fascinating
      adaptations to function. One primary function is to supply nutrients to the
      avascular cartilage, whose chondrocytes are metabolically active but are
      relatively vast distances from the nearest capillary (> 1 cm in the center of a
      human knee). Exchange is facilitated by a high density of fenestrated capillaries
      situated very close to the synovial surface (an arrangement disrupted in
      rheumatoid synovium) with fenestrations preferentially oriented toward the joint
      cavity. Even so, diffusion alone is too slow to supply central chondrocytes with
      glucose. The problem is solved by the synovial microcirculation generating intra
      articular fluid (synovial fluid) that transports glucose by convection during
      joint movement. Synovial fluid is a plasma ultrafiltrate into which hyaluronan
      has been secreted, and it also serves to lubricate the joint. The joint cavity
      offers unusually easy access to the interstitial side of the microcirculation
      because the synovial cell layer is discontinuous, with an interstitial matrix
      between capillary and joint cavity. This allows the experimental study of the
      effect of the extravascular Starling "forces" (hydraulic and colloid osmotic
      pressure) on fluid exchange. One unexpected outcome has been the finding that a
      substantial part of the hydraulic resistance to fluid transport between blood and
      joint cavity resides in the series interstitial layer rather than in the
      capillary wall. Another is that, under appropriate boundary conditions (joint
      angle, etc.) fluid can simultaneously filter into the cavity in some regions
      (synovium directly overlying capillaries) and out of the cavity into subsynovium
      in other regions (synovium in the mesh space between capillaries) to produce a
      turnover of synovial fluid.

PMID- 8748947
TI  - Nitric oxide affects microvascular permeability in the intact and inflamed
      vasculature.
AB  - There is a growing body of evidence that nitric oxide modulates the movement of
      fluid and protein out of the vasculature. However, the results obtained from
      whole organ, single vessel, and endothelial monolayer studies are often not
      consistent. In fact, there is much evidence that endogenous nitric oxide
      increases microvascular permeability and equally compelling evidence to suggest
      that endogenous nitric oxide decreases microvascular permeability. In this review
      we summarize and critically evaluate the data published to date regarding the
      role of nitric oxide as a modulator of microvascular permeability under both
      normal conditions and following exposure to various stimuli. The last section of
      the chapter discusses the importance of nitric oxide as a modulator of
      microvascular permeability in inflammatory conditions. Particular emphasis is
      placed on the stimuli used, the organ systems studied, and the measurements
      performed to investigate the effects of nitric oxide on microvascular
      permeability alterations.

PMID- 8748948
TI  - Microcirculatory homeostasis 1930-1990: insight into microcirculatory
      readjustments provided by studies on the peripheral circulatory insufficiency of
      the shock syndrome.
AB  - The present overview is intended to serve several purposes. It highlights efforts
      over the years to resolve the difficult key issues raised by August Krogh in the
      1930s and by the urgent need created in the 1940s and 1950s by World War II to
      come to grips with the basic problems underlying the collapse of tissue perfusion
      in the syndrome of circulatory shock. The complex operational issues raised by
      circulatory insufficiency at the systemic, as well as the local tissue level,
      during the shock syndrome, are used as a framework to keep in perspective the
      impact of advances in methodology, ultrastructure, and in recent years in
      molecular biology on microvascular research. In view of the current continuing
      need to integrate the newly emerging body of in vitro information into specific
      aspects of the operation of the peripheral vascular tree, emphasis is placed on
      the advances in dealing with data provided by in vivo microscopy of selected
      tissues. This overall review had made it clear that a top priority remains the
      need to separate the effects of systemic and locally derived readjustments, and
      to identify the basis for the substantial differences in cellular behavior
      exhibited by the vascular and perivascular components of the various organs and
      tissues of the body that can serve as predisposing factors in regional
      pathophysiology.

PMID- 8748949
TI  - Type II collagen is a major component of bovine retinal microvessel extracellular
      matrix.
AB  - OBJECTIVE: To determine which interstitial collagen types may be present in
      bovine retinal microvessel extracellular matrix (ECM). METHODS: Dissociated
      bovine microvessels were treated with detergents and the resultant purified ECM
      monitored by transmission electron microscopy (TEM). Pepsin-extracted soluble ECM
      collagens were identified by Western blots. Collagens were further purified by
      neutral salt precipitation and carboxymethyl cellulose (CMC) chromatography
      before cyanogen bromide (CNBr) peptide mapping and two-dimensional peptide
      mapping of CMC-generated fractions. Interstitial collagens were localized by
      immunofluorescence on frozen sections. RESULTS: Transmission electron microscopy
      of detergent-purified microvessel ECM demonstrated numerous 10-50-nm collagen
      fibrils associated with basal laminae regardless of vessel diameter. Western
      blots showed that soluble ECM collagens were strongly positive for type II,
      moderate for type III, and weak for type I. CNBr peptide maps and two-dimensional
      maps of neutral salt and CMC-purified fractions confirmed the presence of type II
      collagen. Immunofluorescence localized type II collagen in large and small
      vessels of the retina. CONCLUSIONS: Type II collagen is an unexpected major
      component of bovine microvessel ECM, whereas types I and III are present in minor
      amounts. Type V collagen is also a substantial ECM component. Accordingly, all
      four types may contribute to a heterogeneous population of collagenous fibrils
      identified by TEM in intact isolated retinal microvessel ECM.

PMID- 8748950
TI  - Visualization of endothelial clefts and nuclei in living microvessels with
      combined reflectance and fluorescence confocal microscopy.
AB  - OBJECTIVE: The cellular basis for spatial heterogeneity along postcapillary
      venules in their response to inflammatory mediators is not understood. To study
      permeability regulatory processes on an individual cell basis in intact
      microvessels, we developed methods to delineate individual endothelial cells
      within living, single perfused microvessels. METHODS: Individual postcapillary
      microvessels in the mesenteries of frogs and hamsters were perfused with chloride
      free Ringer's solutions containing AgNO3 (0.1 g per 100 ml) for 5--10 s. Vessels
      were immediately flushed with Ringer's solution containing serum albumin and some
      vessels subsequently perfused with the fluorescent nucleic acid stain YO-PRO-1 (1
      microM) for 10-15 min. Vessels were imaged in situ using laser scanning confocal
      microscopy. A reflectance image from silver precipitate in the endothelial clefts
      and a fluorescence image of the nuclei were simultaneously recorded. Stacks of
      confocal images were merged and used to reconstruct the three-dimensional
      orientation of endothelial cells. Hydraulic conductivity of some frog mesenteric
      venular vessels, measured before and after perfusion with AgNO3, was used to
      assess the integrity of the vessels. RESULTS: The endothelial cell clefts were
      delineated with a very fine, readily imaged precipitate of silver. Hydraulic
      conductivity measured after AgNO3 perfusion in frog mesenteric venular
      microvessels was not significantly different from control. Vessels showed a
      slight reduction in reactivity to inflammatory stimuli. The three-dimensional
      pattern of endothelial cells in the living vessels was imaged. CONCLUSIONS:
      Combining confocal microscopy with silver staining in single perfused
      microvessels was shown to be an effective means to delineate the three
      dimensional pattern of endothelial cells forming microvessel walls. It enables
      further study of the vascular structure and function relationships at the
      individual cell level in intact microvessels.

PMID- 8748951
TI  - Autoradiographic assessment of blood flow heterogeneity in the hamster heart.
AB  - OBJECTIVE: Provide regional flow measurement in the hearts of small mammals using
      a new, higher-resolution technique based on the deposition of a molecular marker.
      METHODS: We determined the instantaneous extraction and retention of the
      "molecular microsphere" radiolabeled desmethylimipramine in retrogradely perfused
      hamster hearts. In a separate series of experiments, autoradiography was used to
      measure regional myocardial deposition densities in hamster hearts of about 0.5 g
      with spatial area resolution of 16 x 16 microns. RESULTS: Radiolabeled
      desmethylimipramine is almost 100% extracted during a single transcapillary
      passage and is retained in the tissue for many minutes. Autoradiographic images
      demonstrated a spatial flow heterogeneity with standard deviations of 31 +/- 4%
      of the mean flow (N = 5) in 16 x 16 x 20-micronm3 voxels. This is equivalent to
      the projections made using fractal relationships from cruder observations
      obtained with microspheres in the hearts of baboons, sheep, and rabbits.
      CONCLUSIONS: Autoradiography using a molecular deposition marker provides
      quantitative information on myocardial flow heterogeneities with resolution at
      the size of cardiac myocytes. Because the regions resolved are smaller than the
      volume of regions supplied by single arterioles, the results must slightly
      exaggerate the true heterogeneity of regional flows.

PMID- 8748952
TI  - Putrescine: a novel inhibitor of glycosylation-induced cross-links in laminin.
AB  - OBJECTIVE: To determine whether putrescine, a naturally occurring polyamine, is
      able to prevent nonenzymatic glycosylation-induced cross-linking of basement
      membrane components. Cross-linking, leading to the formation of advanced
      glycosylation end products (AGEs) has been proposed as a major mechanism
      contributing to structural and functional changes of the vascular wall, thus
      leading to microangiopathy. METHODS: Laminin, a major basement membrane
      glycoprotein present in the microvasculature, was isolated and incubated in the
      presence of high glucose concentrations, in order to generate an in vitro
      diabetic environment. Putrescine was either present or absent from the incubation
      mixture. Formation of cross-links was assessed by two independent methods: gel
      electrophoresis and development of characteristic fluorescence. RESULTS:
      Putrescine inhibited in a dose-dependent manner the formation of slower mobility
      bands in gel electrophoresis. Quantitation of the development of fluorescence
      characteristic of glycosylation-induced cross-links demonstrated that putrescine
      inhibited the formation of fluorescent products. CONCLUSIONS: Putrescine may be a
      promising compound for inhibition of protein cross-linking and, therefore, could
      be used in the prevention of diabetic microangiopathy.

PMID- 8748953
TI  - Flow-dependent dilation and myogenic constriction interact to establish the
      resistance of skeletal muscle arterioles.
AB  - OBJECTIVE: To test the hypothesis that the diameter of skeletal muscle arterioles
      is determined by the interaction of responses elicited by intravascular pressure
      and flow. METHODS: Experiments were conducted on isolated, cannulated, first
      order arterioles of cremaster muscle of male Wistar rats. The diameter of
      arterioles was followed by videomicroscopy. Perfusion pressures and flows were
      controlled. RESULTS: In the absence of perfusate flow, increases in perfusion
      pressure (from 0 to 120 mm Hg), after initial dilation, elicited endothelium
      independent constrictions of arterioles. At 60 mm Hg of perfusion pressure, the
      active diameter of vessels was 84.9 +/- 1.9 microns. The passive diameter of
      arterioles (Ca2(+)-free solution)was 150.6 +/- 2.4 microns. Increases in
      perfusate flow resulted in a significant upward shift in the pressure-diameter
      curves; in the presence of perfusate flows of 20, 40, and 60 microL/min, the
      constriction of the vessels at a pressure of 60 mm Hg was attenuated by 25.1 +/-
      3.9%, 35.2 +/- 3.0%, and 46.8 +/- 4.4%, respectively. In contrast, the
      corresponding diameter of arterioles at perfusate flows of 10 to 60 microL/min
      was significantly reduced when perfusion pressure was increased from 60 to 80 and
      100 mm Hg (at a flow of 60 microL/min) by 12.0 +/- 4.3% and 37.1 +/- 2.8%,
      respectively. Hence, both flow- and shear stress-diameter curves were
      significantly shifted downward when perfusion pressure increased from 60 to 100
      mm Hg. CONCLUSION: These results demonstrate that an interplay between pressure
      and flow-sensitive mechanisms is an important determinant of the arteriolar
      resistance in skeletal muscle.

PMID- 8748954
TI  - On the acquisition of new declarative knowledge in amnesia.
AB  - In 2 experiments, the acquisition of new declarative knowledge was examined in
      amnesic patients and in 7 groups of controls, with a study-only procedure that
      delayed testing until the conclusion of training. The study-only procedure was
      compared with a standard procedure in which study and test trials alternated
      (study-test). The amnesic patients acquired new factual (declarative) knowledge
      at an abnormally slow rate, learning more with the study-only procedure than with
      the study-test procedure. Controls exhibited the opposite pattern. The advantage
      of the study-only procedure for amnesic patients was related to the presence of
      frontal lobe dysfunction. The 2 groups exhibited a similar ability to use their
      knowledge flexibly, suggesting that the information acquired by amnesic patients
      was based on their residual capacity for declarative memory. In addition, the
      capacity for factual learning in amnesia was proportional to the capacity to
      recollect specific events in the learning session.

PMID- 8748955
TI  - Olfactory-visual associative learning in monkeys depends on intrahemispheric
      olfactory-visual interaction.
AB  - Three Cynomolgus monkeys (Macaca fasicularis) learned a series of food-visual
      conditional discrimination problems. In each problem, 1 of 2 possible food items
      was presented at the beginning of each trial and acted as an instruction cue as
      to which of 2 visually distinct stimulus objects the monkey must displace on that
      trial to obtain a further food reward. Following surgical disconnection of
      olfactory-visual intrahemispheric interaction, the monkeys were unable to use
      olfactory properties of the food items to guide visual choices. These results
      show both that olfactory differences between foodstuffs are a powerful olfactory
      stimulus, which can enter into cross-modal association with visual stimuli, and
      that this association depends on an intrahemispheric pathway of olfactory-visual
      interaction.

PMID- 8748956
TI  - A comparison of kainic acid plus colchicine and ibotenic acid-induced hippocampal
      formation damage on four configural tasks in rats.
AB  - J.W. Rudy and R.J. Sutherland (1989) suggested that the hippocampal formation
      (HF) is necessary for performance of configural tasks and that rats with kainic
      acid + colchicine (K-C) damage to the HF were impaired on the negative patterning
      problem (A+, B+, AB-). However, M. Gallagher and P.C. Holland (1992) found spared
      performance on a similar task (AC+, B+, AB-, C-) when ibotenic acid (IBO) was
      used. This study compared the effects of K-C- and IBO-induced HF damage on 4
      configural tasks: (a) negative patterning, (b) the Gallagher-Holland task, (c)
      transverse patterning, and (d) place learning. Rats with IBO lesions performed
      like controls on the Gallagher-Holland task (replicating M. Gallagher & P.C.
      Holland) but were impaired on negative patterning, transverse patterning, and
      place learning. In contrast, rats with K-C lesions were impaired on all 4 tasks.
      The implications of these results for theories of HF function are discussed.

PMID- 8748957
TI  - Functional differences between the prelimbic and anterior cingulate regions of
      the rat prefrontal cortex.
AB  - The effects of reversible lidocaine-induced lesions of 2 subregions of the rat
      medial prefrontal cortex (mPFC) were examined on a series of cognitively based
      foraging behaviors on a radial-arm maze. Lesions of the prelimbic (PL) or
      anterior cingulate (AC) cortex prior to the retention phase of a delayed-foraging
      task disrupted performance differentially; rats with PL lesions visited arms in a
      random manner, whereas rats with AC lesions revisited previously baited arms
      preferentially. Rats with AC lesions were also impaired on a single-trial
      foraging task; they made numerous revisits to previously baited arms. PL lesions
      had no effect on performance of this task in well-trained rats. However, rats
      trained on the 2-phase task did not adapt to a new foraging strategy after a PL
      lesions, when they were switched unexpectedly to the single-trial foraging task.
      These data demonstrate functional heterogeneity within the rat mPFC and suggest
      that the PL is involved in processes through which recently acquired information
      is used to organize and modify foraging behavior, whereas the AC may play an
      important role in response flexibility.

PMID- 8748958
TI  - Pyruvate infusions into the septal area attenuate spontaneous alternation
      impairments induced by intraseptal morphine injections.
AB  - Glucose infusions into the medial septal area attenuate memory impairments
      produced by concurrent intraseptal morphine injections. One possible explanation
      for these effects of glucose on memory is that the treatment modulates regional
      energy metabolism. As a test of this hypothesis, the present experiment
      determined whether intraseptal pyruvate injections could attenuate a spontaneous
      alternation impairment seen after intraseptal morphine injections. Intraseptal
      injections of morphine (4.0 nmol) 30 min prior to testing produced spontaneous
      alternation scores significantly lower than those in control groups. Morphine
      injections near, but outside, the septal region did not impair spontaneous
      alternation performance. The morphine-induced impairment was similarly reversed
      by coadministration of either glucose (18 nmol) or pyruvate (18 nmol) into the
      septum. These findings suggest that glucose may act through the tricarboxylic
      acid cycle by increasing the availability of ATP, augmenting the synthesis of
      certain neurotransmitters, or both.

PMID- 8748959
TI  - Spatial- and locomotion-related neural representation in rat hippocampus
      following long-term survival from ischemia.
AB  - Spatial and locomotion-related behavioral correlates of hippocampal cell
      discharge were compared between ischemic and sham-control rats performing a
      spatial maze. Ischemic rats showed impaired choice accuracy during maze
      acquisition, but not during asymptote performance. Single-unit correlates during
      asymptote performance revealed enhanced spatial selectivity of CA2/3 complex
      spike cells coincident with attenuated place-specific firing by hilar complex
      spike or subicular cells. Responsivity to locomotion state by stratum granulosum
      interneurons was exaggerated, and locomotion-induced changes in firing of hilar
      and subicular interneurons was reduced. Ischemic rats showed recovered spatial
      learning abilities as evidenced by the fact that acquisition of the spatial task
      in a second environment was not impaired. Because representational reorganization
      was also observed in ischemic, maze-naive rats, brain injury per se appears to
      change information coding schemes.

PMID- 8748960
TI  - Overt orienting in the rat: parametric studies of cued detection of visual
      targets.
AB  - Covert shifts of visual attention in space have been quantified by measuring the
      effects of visual cues on the detection of visual targets in humans and monkeys
      maintaining visual fixation. These observations of "covert orienting" have
      provided important information regarding the neurobiology of visual attention in
      primates. This article describes a cued spatial target detection task for
      physically unrestrained rats. Valid cues (spatially contiguous with the target)
      enhanced target detection, and invalid cues (spatially discontiguous with the
      target) degraded target detection. Both visual and auditory cues were effective.
      These validity effects could not be explained by stimulus additivity or response
      preparation mechanisms, whereas a cue-independent "alerting effect" appeared to
      reflect response preparation. The effects compare favorably with primate work and
      suggest that this method may enable assessment of visual attention shifts in
      rats.

PMID- 8748961
TI  - Connections to cerebellar cortex (Larsell's HVI) in the rabbit: a WGA-HRP study
      with implications for classical eyeblink conditioning.
AB  - Conditioned eyeblink responses are presumably learned in the cerebellum and
      relayed to motoneurons by way of the red nucleus. Projections from the red
      nucleus to cerebellar cortex (Larsell's lobule HVI) could be important for
      shaping temporally adaptive features of the conditioned response. Rabbits that
      had pipettes containing wheat germ agglutinated horseradish peroxidase (WGA-HRP)
      implanted unilaterally into HVI showed retrograde labeling of neurons within
      subregions of the contralateral red nucleus implicated in eyeblink conditioning
      by lesioning and recording studies. Retrogradely labeled neurons were also
      observed in the pontine nuclei, inferior olive, and spinal trigeminal nucleus
      pars oralis. Projections to HVI provide a possible neural substrate for
      implementing time-derivative computational models of learning in the cerebellum.
      Time-derivative models are capable of describing the timing and topography of
      conditioned responses.

PMID- 8748962
TI  - Learning of physiological responses: II. Classical conditioning of the
      baroreflex.
AB  - The baroreflex can be classically conditioned. In neuromuscular blocked (NMB)
      rats, electrical stimulation of the aortic depressor nerve (ADN) and dopamine
      produced blood pressure rise were effective unconditioned stimuli (UCS) for
      auditory discriminative classical conditioning. The conditioned response (CR)
      pattern (bradycardia, vasodilatation, and hypotension > 10 torr) closely
      resembled that of the unconditioned baroreflex. Conditioned stimulus (CS)
      specificity was demonstrated by discrimination of baroreflex-associated and
      nonassociated auditory stimuli, and also by elaborating depressor and pressor CRs
      to auditory CSs, which respectively had been associated with either baro-afferent
      (depressor) or tail-shock (pressor) UCSs. The conditioned-baroreflex-magnitude
      increased with trials. These findings support quantitative models in which CRs
      interact with and calibrate the gain and dynamic properties of natural reflexes.

PMID- 8748963
TI  - Effects of peripherally administered corticotropin-releasing factor (CRF) and a
      CRF antagonist: does peripheral CRE activity mediate behavior of guinea pig pups
      during isolation?
AB  - Guinea pig pups vocalized and ambulated when first isolated in a test cage; at 1
      and 24 hr, levels of these behaviors had waned, and pups frequently exhibited a
      crouched stance, eye-closing, and piloerection. Injection (s.c.) of corticotropin
      releasing factor (CRF) prior to isolation diminished the initial vocalization and
      locomotor responses and induced pups to exhibit the crouched stance, eye-closing,
      and piloerection at the beginning of the isolation period. Pretreatment with a
      CRF-receptor antagonist reversed the behavioral effects of CRF. CRF had no effect
      on blood pressure. Thus, s.c. CRF produced the same behavioral profile as seen
      with the passage of time in untreated isolated pups. The behavioral effects
      appeared to be CRF-receptor-mediated events and were not secondary to
      hypotension. These results support the hypothesis that during prolonged
      isolation, high or sustained peripheral CRF activity modulates behavior.

PMID- 8748964
TI  - Neuropeptides and thirst: the temporal response of corticotropin-releasing
      hormone and neurotensin/neuromedin N gene expression in rat limbic forebrain
      neurons to drinking hypertonic saline.
AB  - The authors have demonstrated in rats that the ingestion of hypertonic saline for
      5 days provides an increasingly complex dehydrating stimulus to the rats.
      Initially, the stimulus leads to cellular dehydration, but extracellular
      dehydration develops as ingestion continues beyond 3 days. The initial cellular
      dehydration provokes modifications to corticotropin-releasing hormone and
      neurotensin/neuromedin N messenger RNAs (mRNAs) in some neurons of the limbic
      forebrain, changes that are either maintained or are modified as extracellular
      dehydration develops. These changes in mRNA content occur in neurosecretory
      neurons as well as in neurons in hypothalamic and telencephalic regions
      associated with behavior and autonomic regulation. The authors propose that
      alterations in peptide mRNAs are allied to altered neuronal signaling processes
      that direct the different components of the homeostatic response to dehydration.

PMID- 8748965
TI  - A time-structured analysis of hypothalamically induced increases in self-grooming
      and activity in the rat.
AB  - Stressors and different manipulations of the paraventricular nucleus of the
      hypothalamus (PVH) increase self-grooming in the rat. To assess the effect of
      these PVH manipulations on the timing of grooming in relation to other ongoing
      behavior, the authors describe these behavioral responses by a time-structured
      model. The authors show the following: (a) Behavior in each treatment group can
      be described by a semi-Markov model. Effects of treatments can be described as
      changes in the parameters of this model, which reflect the tendencies to start
      and stop grooming and other activities. (b) The PVH manipulations increase self
      grooming by increasing the tendencies to start grooming or by extending the
      period during which grooming occurs. (c) Grooming responses are accompanied by an
      increase in activity. (d) Different PVH manipulations change the temporal
      structure of behavior differentially, suggesting that distinct mechanisms within
      the PVH are involved in the precise timing of grooming in relation to other
      activities.

PMID- 8748966
TI  - Lateral habenula neurons are necessary for the hormonal onset of maternal
      behavior and for the display of postpartum estrus in naturally parturient female
      rats.
AB  - In 16-day pregnant, hysterectomized-ovariectomized and estradiol benzoate-treated
      rats, cytotoxic lesions of the lateral habenula (Lhb) produced severe deficits in
      maternal behavior (K.P. Corodimas, J.S. Rosenblatt, M.E. Canfield, & J.I.
      Morrell, 1993). To determine if deficits could be found in parturient rats,
      females were bilaterally injected with kainic acid (KA) to produce cytotoxic
      lesions of the Lhb. Controls either received bilateral KA-induced lesions to the
      hippocampus or were unoperated. All females maintained their pregnancies,
      underwent parturition, and were tested for maternal behavior (pup retrieval,
      nursing, and nestbuilding), general activity, and oromotor carrying. Females with
      lesions of the Lhb had severe disruptions of all components of maternal behavior
      and postpartum estrus. These results extend previous findings that the Lhb is
      involved in the hormonal onset of maternal behavior and also demonstrate that the
      Lhb supports the display of postpartum estrus.

PMID- 8748967
TI  - Ontogeny of morphine withdrawal in the rat.
AB  - The present studies examined behavioral changes during precipitated morphine
      withdrawal in 7- to 42-day-old rat pups. One group of rats was injected with
      morphine sulfate (10.0 mg/kg) twice daily for 6.5 days. Another group of 7-day
      old rats received a lower dose of morphine (3.0 mg/kg). Controls were saline
      injected or untreated litters (7-day-old pups only). On Day 7, a target pup was
      injected with saline or naltrexone (0.3-10.0 mg/kg). Preweaning pups were
      observed in a warm chamber with the litter. Forty-two-day-old rats were tested
      individually. Morphine-treated pups tested with naltrexone showed significant
      alterations in behavior that varied at different ages. For example, rolling,
      stretching, and head and paw moves were observed at the younger ages, whereas
      burrowing, diarrhea, jumps, teeth chatter, and wet dog shakes occurred in the
      older rats. These data indicate that morphine-abstinent rats demonstrate
      withdrawal signs that are within the developmental repertoire of the rat.

PMID- 8748968
TI  - Genetic analysis of the corticosterone response to ethanol in BXD recombinant
      inbred mice.
AB  - The genetic control over the corticosterone response to ethanol (EtOH) and its
      possible relationship to other EtOH-related traits was examined using BXD
      recombinant inbred (RI) strains derived from an F2 cross of C57BL/6J (B6) and
      DBA/2J (D2) progenitor strains. Quantitative trait locus (QTL) analysis of
      corticosterone levels 1 hr following EtOH suggested the influence of a single
      major gene on this trait. Two loci were predicted to account for 47% of the
      genetic variance in plasma corticosterone levels 6 hr following EtOH, whereas 3
      loci were predicted to account for 78% of the genetic variance in corticosterone
      levels 7 hr following EtOH. Markers associated with corticosterone levels 7 hr
      following EtOH and corrected corticosterone levels 6 hr post-EtOH overlapped with
      ones found to influence acute and chronic EtOH withdrawal severity, suggesting
      some degree of common genetic determination between these traits. Overall these
      results indicate that gene action significantly influences stress responsiveness
      and suggest possible chromosomal locations of these genes.

PMID- 8748969
TI  - Pyrithiamine-induced thiamine deficiency impairs object recognition in rats.
AB  - Pyrithiamine-induced thiamine deficiency (PTD) in rats is used to model the
      etiology, diencephalic neuropathology, and memory deficits of Korsakoff's
      amnesia. We assessed the performance of rats exposed to PTD on a test of object
      recognition--nonrecurring-items delayed nonmatching-to-sample (DNMS). PTD
      produced thalamic lesions similar to those of Korsakoff's amnesics and similar to
      those previously observed in PTD rats. PTD rats required more trials to master
      DNMS at a 4-s retention delay than did controls, and after they had done so, they
      performed more poorly than controls at delays of 15, 30, 60, and 120 s. DNMS
      deficits were also observed in PTD rats that received training prior to PTD
      treatment. These findings support the validity of the PTD rat model of
      Korsakoff's disease by demonstrating that PTD rats display object-recognition
      deficits that are similar to those reported in Korsakoff amnesics.

PMID- 8748970
TI  - Ethanol neurobehavioural teratogenesis and the role of L-glutamate in the fetal
      hippocampus.
AB  - The purpose of this article is to review the current state of knowledge of
      ethanol neurobehavioural teratogenesis and its postulated mechanisms. The review
      comprises an examination of ethanol teratogenesis in the human, including the
      fetal alcohol syndrome, and in experimental animals. Several current proposed
      mechanisms of ethanol neurobehavioural teratogenesis are critically assessed,
      including the role of acetaldehyde as the proximate metabolite of ethanol; fetal
      hypoxia; placental dysfunction; fetal prostaglandin metabolism; and action of
      ethanol on developing neurons in the fetal brain, including the hippocampus, one
      of ethanol's main target sites. The effect of ethanol on the release of L
      glutamate, an excitatory amino acid neurotransmitter, in the fetal hippocampus is
      described, and the role of L-glutamate in ethanol teratogenesis involving the
      hippocampus is discussed. A novel mechanism for abnormal neuronal development in
      the fetal hippocampus produced by prenatal ethanol exposure is presented, and
      future experiments to test this hypothesis are proposed.

PMID- 8748971
TI  - Responses of human motoneurons to Ia inputs: effects of background firing rate.
AB  - The effects of synchronous Ia volleys on the firing probability of repetitively
      firing human motoneurons were examined at fast and slow firing rates. Ia
      afferents of either the median or the posterior tibial nerve were stimulated,
      while single motor unit activity was recorded from the homonymous muscles.
      Motoneuron responses to the Ia inputs were quantified by measurement of the
      magnitude of the short latency excitatory peak in peristimulus time histograms
      (PSTHs). When the stimuli were given at random with respect to the times of motor
      unit spikes, the magnitude of the PSTH peak (response probability) was
      significantly lower at a faster firing rate. In the "triggered" mode of
      stimulation, stimuli were given at various known times during the interspike
      interval. In this mode the response probability to the input increased
      monotonically as the stimuli were delivered progressively later during the
      interspike interval. The response probability at a fixed delay with respect to
      the triggering spike was higher at the faster firing rate. The results obtained
      with the two modes of stimulation are not in contradiction and both may be
      explained by the nature of membrane voltage trajectories and ionic conductances
      during the interspike interval described for repetitively firing cat motoneurons.

PMID- 8748972
TI  - Regulatory peptides as modulators of vagal influence on cardiac rhythm.
AB  - When the right vagus nerve of anesthetized cats was stimulated with repetitive
      bursts of pulses, decelerated heart rate became synchronized to the rhythm of the
      vagal bursts. Each burst applied to the vagus was followed by a single heart
      contraction. Within defined limits an increase in the frequency of vagal bursts
      evoked a proportional acceleration of the heart, whereas a decreased frequency
      diminished the heart rate. Therefore, over the range of synchronization the heart
      rate was precisely controlled by changing the vagal stimulation rate. We
      concluded that the chronotropic effect evoked by vagal bursts was composed of two
      functionally different types of influence, namely, inhibitory tonic and
      synchronizing. The vagotropic influence of intravenously injected regulatory
      peptides was found to be selective for either the tonic or synchronizing
      component. For instance, dalargin (D-Ala2-Leu5-Arg6-enkephalin) and neokyotorphin
      selectively diminished the inhibitory tonic vagal influence, whereas delta sleep
      inducing peptide and neurotensin potentiated it. The magnitude of synchronizing
      vagal influence was not modified by these peptides. In contrast, secretin
      selectively inhibited the synchronizing vagal effect, but the tonic one was not
      affected. Somatostatin potentiated the synchronizing effect but diminished the
      tonic one. These data support the hypothesis that certain regulatory peptides can
      modulate the effects of repetitive vagal bursts on pacemaker activity.

PMID- 8748973
TI  - Zinc deficiency impairs whole-body accumulation of polyunsaturates and increases
      the utilization of [1-14C]linoleate for de novo lipid synthesis in pregnant rats.
AB  - Zinc deficiency impairs the metabolism of polyunsaturates, but the degree to
      which its effects are independent of food intake are still in question. Identical
      amounts of a semiliquid control diet (26.4 mg zinc/kg) or moderately zinc
      deficient diet (3.2 mg zinc/kg) were tube fed to rats for 11 days during the
      second half of pregnancy to evaluate the specific effects of zinc deficiency on
      maternal utilization and fetal accumulation of polyunsaturates. The whole body
      fatty acid balance method was used to determine net accumulation of
      polyunsaturates and their whole-body disappearance. Incorporation of 14C from [1
      14C]linoleate into maternal and fetal lipid classes was also studied on days 20
      21. At term, zinc-deficient rats had significantly higher whole-body
      disappearance of linoleate and alpha-linolenate and lower accumulation of n-6 and
      n-3 long-chain polyunsaturates. Zinc-deficient rats had higher 14C activity in
      free cholesterol, saturates, and monounsaturates in several maternal organs but
      not in the fetuses. We conclude that during pregnancy, moderate zinc deficiency
      not affecting food intake or weight gain still alters whole-body metabolism of
      linoleate and alpha-linolenate towards increased beta-oxidation and also
      increases the utilization of carbon from linoleate for de novo lipid synthesis.

PMID- 8748974
TI  - Antiarrhythmic effects of ceruloplasmin during reperfusion in the ischemic
      isolated rat heart.
AB  - The ability of ceruloplasmin, an important serum antioxidant, to reduce the
      vulnerability of the isolated rat heart to reperfusion arrhythmias has been
      investigated. Bovine plasma ceruloplasmin was purified by chromatography on
      aminoethyl-agarose. Isolated rat hearts were submitted to 15 min of regional
      ischemia and 10 min of reperfusion. The dose-effect relationship and the role of
      ceruloplasmin conformational integrity in cardioprotection were established by
      treatment of ischemic hearts with ceruloplasmin at various concentrations (0.25,
      0.5, 1, and 2 microM) and at different degrees of conformational integrity
      (A610/A280 = 0.02, 0.04, and 0.06), 5 min before reperfusion. Deferoxamine (20
      500 microM) was used as a positive control. As negative controls we used
      chemically inactivated ceruloplasmin (1 microM), heat-denatured ceruloplasmin (1
      microM), and albumin (1-4 microM). In the control group during the first 5 min of
      reperfusion, the incidence of total ventricular fibrillation was 100% and of
      irreversible ventricular fibrillation was 83%. The incidence of reversible and
      irreversible ventricular fibrillation was significantly decreased in the
      ceruloplasmin-treated groups in both a dose and molecular integrity dependent
      manner. Ceruloplasmin had no effect on the incidence of ventricular tachycardia.
      Deferoxamine reduced the incidence of ventricular fibrillation to the same degree
      as ceruloplasmin but at concentrations much higher than those of ceruloplasmin.
      Chemically inactivated ceruloplasmin, heat-denatured ceruloplasmin, and albumin
      had no protective effects on reperfusion-induced arrhythmias.

PMID- 8748975
TI  - Endothelin receptor subtypes in mesenteric vascular smooth muscle cells of
      spontaneously hypertensive rats.
AB  - Calcium responses to the endothelin B receptor (ETB) selective agonist IRL-1620
      (IRL) and to endothelin 1 (ET-1) in the absence and presence of the endothelin A
      receptor (ETA) antagonist BQ-123 were determined in primary cultured unpassaged
      vascular smooth muscle cells derived from mesenteric resistance vessels of 3-, 9
      , and 17-week-old spontaneously hypertensive rats (SHR), Wistar rats, and Wistar
      Kyoto (WKY) rats. Intracellular free calcium concentration ([Ca2+]i) was measured
      microphotometrically and by digital imaging using fura 2 methodology. ET receptor
      affinity and density were determined in membrane preparations from the mesenteric
      vascular bed from these rats. Binding studies were performed using [125I]ET-1 in
      the presence of increasing concentrations of ET-1, BQ-123, or IRL. Basal [Ca2+]i
      was significantly greater (p < 0.01) in adult SHR compared with age-matched
      normotensive groups. IRL (10(-7) mol/L) and ET-1 (10(-9) mol/L) increased [Ca2+]i
      in cells from all strains of all age groups. Responses were significantly lower
      (p < 0.05) in vascular smooth muscle cells from 9- and 17-week SHR compared with
      cells from age-matched Wistar and WKY rats. Concentration-response curves for IRL
      were blunted in cells from 17-week SHR versus cells from WKY rats. The selective
      ETA receptor antagonist BQ-123 (10(-7)-10(-5) mol/L) had no effect on IRL-induced
      [Ca2+]i but significantly reduced ET-1-induced [Ca2+]i by 135 +/- 4, 80 +/- 6,
      and 91 +/- 4 nmol/L in cells from 17-week SHR, WKY, and Wistar groups,
      respectively. The selective ETB receptor antagonist BQ-788 (10(-6) mol/L)
      significantly reduced ET-1-induced [Ca2+]i responses in 17-week rats. The Bmax
      for ET-1 binding was significantly lower in mesenteric artery membrane
      preparations from 17-week SHR (627 +/- 163 fmol/mg protein) compared with WKY and
      Wistar rats (1190 +/- 43 and 1059 +/- 55 fmol/mg protein, respectively). These
      data demonstrate the presence of both ETA and ETB receptors in rat mesenteric
      vascular smooth muscle cells. In adult SHR, reduced responses of vascular smooth
      muscle cells to IRL, which represents ETB-mediated effects, and to ET-1, may be
      partly due, as demonstrated in the binding studies, to lower ET receptor density
      than in normotensive rats.

PMID- 8748976
TI  - Quantification of the hemolysis associated with use of T-61 as a euthanasia agent
      in rabbits--a comparison with Euthanyl (pentobarbital sodium) and the impact on
      serum hexosaminidase measurements.
AB  - Albino rabbits (2-2.3 kg) were euthanized with T-61R (N-[2-(m-methoxyphenyl)-2
      ethylbutyl-(1)-]-gamma-hydroxybutyram ide, 200 mg/mL; 4,4'-methylene-bis
      (cyclohexyltrimethylammonium iodide), 50 mg/mL; tetracaine hydrochloride, 5
      mg/mL; 0.2-1.0 mL/kg, i.v.) or EuthanylR (pentobarbital sodium, 100-240 mg/kg,
      i.v.) at 15:00 h, and samples of arteriovenous blood or venous blood were
      collected. The time to loss of consciousness was dose dependent for T-61, ranging
      from 7 to 1 s or less. Serum obtained after T-61 euthanasia, but not after
      Euthanyl, was routinely contaminated with measurable hemoglobin levels (up to an
      estimated 3 mg/mL). The extent of hemolysis increased with increasing T-61 doses.
      The activity of hexosaminidase in the serum (determined by hydrolysis of a
      methylumbelliferyl substrate at pH 4.6) was up to 80% lower in sera obtained
      after the use of T-61 compared with sera obtained after the use of Euthanyl or
      without euthanasia drugs. The reduction in measurable activity appears to be due
      to interference, by hemoglobin, in the fluorescence measurements of the
      methylumbelliferol reaction product (with threshold effects being detected at 0.1
      mg/mL). Standardization of serum volumes used in these types of enzyme assays and
      reporting on hemoglobin levels is thus recommended.

PMID- 8748977
TI  - Norepinephrine induces expression of c-fos mRNA through the alpha-adrenoceptor in
      rat aortic rings.
AB  - We examined whether norepinephrine at pharmacologically relevant doses induces
      increased expression of c-fos mRNA in rat aortic rings. c-fos mRNA was expressed
      at norepinephrine concentrations known to cause minimum and maximum contraction
      of rat aorta in vitro. At the concentration known to cause maximum contraction,
      norepinephrine produced a marked and sustained increase of c-fos mRNA expression.
      Induction of c-fos was blocked completely by the alpha 1-adrenergic antagonist
      prazosin, partially by the alpha 2-adrenergic antagonist yohimbine, and not at
      all by the beta-adrenergic antagonist propranolol. A prazosin inhibition curve
      showed that 1 nmol/L prazosin inhibited 10 micromol/L norepinephrine induced c
      fos expression by 40%. At the pharmacologic dose known to cause maximum
      contraction, norepinephrine induces c-fos mRNA expression through the alpha
      adrenoceptor in rat aortic rings.

PMID- 8748978
TI  - Effect of sympathectomy on inotropic responsiveness to alpha-adrenoceptor
      stimulation in developing mouse myocardia.
AB  - Effects of postnatal sympathectomy on inotropic responsiveness to alpha
      adrenoceptor stimulation were examined in mouse myocardia to determine whether
      the developmental conversion of alpha-adrenoceptor-mediated inotropic responses
      from positive to negative is triggered by sympathetic innervation. Sympathectomy
      was performed chemically by consecutively administering 6-hydroxydopamine for 14
      days after birth and confirmed by the absence of inotropic responses to tyramine.
      In newborn myocardia, phenylephrine, in the presence of propranolol, produced
      concentration-dependent positive inotropic responses. Three weeks after birth,
      phenylephrine, in the presence of propranolol, produced concentration-dependent
      negative inotropic responses, both in control and in sympathectomized myocardia;
      no difference was observed between the two groups of mice in the maximum decrease
      in contractile force produced by phenylephrine. The sensitivity (pD2 value) to
      phenylephrine was significantly higher in sympathectomized myocardia. In
      conclusion, sympathetic innervation of the mouse ventricular myocardium is not
      required for the developmental conversion of the alpha-adrenoceptor-mediated
      inotropic response from positive to negative.

PMID- 8748979
TI  - Glucagon increases medullary interstitial electrolyte concentration in rat
      kidney.
AB  - In anesthetized rats, tissue electrical admittance of the inner medulla (a
      measure of total ion concentration in the interstitium), medullary blood flow
      (laser Doppler technique), and renal clearances were measured simultaneously
      before and during i.v. infusion of glucagon at 110 and 330 ng.min-1.kg-1 body
      weight. Admittance increased modestly, 5.4% after a large glucagon dose (p <
      0.01), whereas medullary blood flow was stable. Glomerular filtration rate
      increased transiently and then fell during high-dose glucagon infusion. The
      increase in tissue electrolyte (mostly NaCl) concentration in the medulla
      observed with stable medullary blood flow and decreasing glomerular filtration
      rate indicates that stimulation of NaCl reabsorption in the medullary ascending
      limb of Henle's loop by glucagon was the mechanism underlying augmentation of
      medullary ionic hypertonicity. This suggests that glucagon can contribute to the
      urine concentration process.

PMID- 8748980
TI  - Temporal constraints in associative synaptic plasticity in hippocampus and
      neocortex.
AB  - We present comparative experimental evidence for the induction of synaptic
      potentiation and depression in organotypic cultures of hippocampus and in visual
      cortex in vitro and in vivo. The effects of associative pairings on the efficacy
      of synaptic transmission are analyzed as a function of the temporal delay between
      presynaptic activity and post-synaptic changes imposed in membrane potential.
      Synchronous association at a low temporal frequency (< 0.5 Hz) between
      presynaptic input and postsynaptic depolarization resulted in homosynaptic
      potentiation of functionally identified postsynaptic potentials in the three
      types of preparation. Synchronous pairing of afferent activity with
      hyperpolarization of the postsynaptic cell resulted in homosynaptic depression in
      visual cortex in vivo and in vitro. An associative form of depression was induced
      in hippocampus when the test input was followed repeatedly with a fixed-delay
      postsynaptic depolarization imposed either by intracellular current injection or
      synaptically. The latter process might play a significant role in heterosynaptic
      plasticity in visual cortex in vivo and in vitro, if it is assumed that
      associative depression still operates in visual cortex a few seconds after the
      initial surge of calcium in the postsynaptic cell. We conclude that the precise
      timing between presynaptic activity and polarization changes in postsynaptic
      membrane potential up- and down-regulates the efficacy of active pathways.

PMID- 8748981
TI  - Metabotropic glutamate receptors and visual cortical synaptic plasticity.
AB  - Two forms of use-dependent synaptic plasticity, called long-term potentiation
      (LTP) and long-term depression (LTD), can be elicited in the visual cortex
      following different paradigms of electrophysiological stimulation. These
      neurobiological phenomena often are considered as necessary components of models
      for the alteration in function of the nervous system that must occur at some
      level for the establishment and (or) maintenance of memory engrams, for learning
      processes, or for the consolidation of active neural connections and regression
      of inactive contacts in the developing brain. It has been postulated that for LTP
      and LTD to be produced in the hippocampus, activation of a particular subtype of
      excitatory amino acid receptor, the metabotropic receptor, is a critical
      requirement. Only recently has it become possible to test this hypothesis
      directly, as a new compound, (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG),
      has been introduced and the suggestion made that it selectively antagonizes the
      metabotropic receptor. This substance has been tested in the present study on
      responses recorded from slices of rat visual cortex and has been found both to
      block the activation of the metabotropic receptor and to interfere selectively
      with the form of synaptic plasticity called LTD. It thus appears from the
      experiments reported in this paper as though the metabotropic receptor subtype
      that is blocked by MCPG is required for the expression of LTD but not for the
      expression of LTP, in the visual cortex of adult rats.

PMID- 8748982
TI  - Adult plasticity in the visual system.
AB  - When visual cortical neurons in adult mammals are deprived of their normal
      afferent input from retinae, they are capable of acquiring new receptive fields
      by modifying the effectiveness of existing intrinsic connections, a basis for
      topographic map reorganization. To gain insights into the underlying mechanisms
      and functional significance of this adult plasticity, we measured the spatial
      limits and time course of retinotopic map reorganization. We also determined
      whether reactivated neurons exhibit normal receptive field properties. We found
      that virtually all units in the denervated zone of cortex acquired new receptive
      fields (i.e., there were no silent areas in the cortex) and map reorganization
      can take place within hours of deafferentation provided that retinal lesions are
      relatively small (< 5 degrees). Furthermore, after long periods of recovery,
      reactivated units exhibited strikingly normal selectivity to stimulus
      orientation, direction of movement, and spatial frequency if relatively high
      contrast stimuli were used. However, responsiveness of these neurons, measured in
      terms of the maximum response amplitude and the contrast threshold, was clearly
      reduced. Thus, contrary to traditional belief, the adult visual cortex is capable
      of exhibiting considerable plasticity, and reactivated neurons are capable of
      contributing to an analysis of a visual scene.

PMID- 8748983
TI  - Spatial reciprocity of connections between areas 17 and 18 in the cat.
AB  - We examined whether the interconnections between areas 17 and 18 are spatially
      reciprocal, i.e., whether a column of cells in area 17 receives from the same
      region of area 18 as it sends projections to, and vice versa. We addressed this
      question by making side by side injections of retrograde fluorescent tracers in
      area 18, calculating the convergence and divergence of the connections from area
      17 to 18. We compared these values with previously reported values of divergence
      and convergence of the projections from area 18 to area 17. The results
      demonstrate that there is a good match between the convergence and divergence of
      the area 17 to area 18 connection and, respectively, the divergence and
      convergence of the reverse connection. We confirmed directly the spatial
      reciprocity by injecting simultaneously in area 17 a retrograde and an
      anterograde tracer and by analyzing quantitatively the density of anterograde and
      retrograde labeling across the surface of area 18. There was an excellent match
      between the density maps of retrogradely labeled cells and anterogradely labeled
      axon terminals in area 18. Connections between areas 17 and 18 therefore exhibit
      large degrees of convergence and divergence and are spatially reciprocal. Thus, a
      given column of cells within one of these two areas is reciprocally
      interconnected with a large region of the opposite area. Such an organization may
      provide the basis for synchronization of firing of neurons across these two
      areas, as revealed by cross-correlation studies.

PMID- 8748984
TI  - Abnormal spatial but normal temporal resolution in the Siamese cat: a behavioral
      correlate of a genetic disorder of the parallel visual pathways.
AB  - Six ordinary and one Siamese cat were tested for spatial frequency contrast
      sensitivity and for flicker discrimination thresholds. The Siamese cat was
      markedly impaired in the former task but performed normally in the latter. This
      result is consistent with single-cell physiological evidence showing an
      abnormally high Y/X cell ratio in the area centralis of Siamese cats. Under a
      more general perspective, this genetically related dissociation of visual
      impairments confirms the idea of parallel pathways subserving spatial and
      temporal resolution, respectively.

PMID- 8748985
TI  - A method to study changes in eye-related columns in the visual cortex of kittens
      during and following early periods of monocular deprivation.
AB  - An immunohistochemical method that exploits the rapid light-evoked expression of
      Fos, the protein product of the immediate early gene, c-fos, to visualize eye
      related columns in the visual cortex, has been used to provide preliminary data
      on the relative innervation of the cortex by the two eyes of monocularly deprived
      kittens and the speed of the changes that occur afterward during reverse
      occlusion. In contrast to conventional anatomical techniques, the method allows
      both cellular resolution and documentation of the dimensions of eye-related
      columns through the depth of the cortex. In kittens monocularly deprived from
      near birth, Fos-immunoreactive neurones were observed in oval or circular
      patches, the size of which decreased as the duration of deprivation was increased
      from 4 to 6 weeks. Following reverse occlusion at 5 weeks of age, the size of the
      patches increased rapidly so that after 4 days their area had approximately
      tripled. In addition to providing possible insights into the anatomical
      underpinnings of the puzzling behavioural effects that occur following
      termination of short periods of reverse occlusion, the method can be used to
      investigate the temporal order of the anatomical effects of monocular deprivation
      in different cortical layers.

PMID- 8748986
TI  - Development and plasticity of the neural circuitry underlying visual recognition
      memory.
AB  - In adult monkeys, visual recognition memory, as measured by the delayed
      nonmatching to sample (DNMS) task, requires the interaction between inferior
      temporal cortical area TE and medial temporal lobe structures (mainly the
      entorhinal and perirhinal cortical areas). Ontogenetically, monkeys do not
      perform at adult levels of proficiency on the DNMS task until 2 years of age.
      Recent studies have demonstrated that this protracted development of visual
      recognition memory is due to an immaturity of the association areas of the
      neocortex rather than the medial temporal lobe. For example, lesions of the
      medial temporal lobe structures in infancy or in adulthood yield profound and
      permanent visual recognition loss, indicating that the medial temporal lobe
      structures operate early in life to sustain visual memory. In contrast, early
      lesions of area TE, unlike late lesions, result in a significant and long-lasting
      sparing of visual memory ability. Further evidence for neocortical immaturity is
      provided by studies of the development of opiatergic and cholinergic receptors,
      of the maturation of metabolic activity, and of the connectivity between inferior
      temporal areas TE and TEO and cortical and subcortical structures. Together these
      results indicate greater compensatory potential after neonatal cortical than
      after neonatal medial temporal removals. In support of this view, early damage to
      area TE leads to the maintenance of normally transient projections as well as to
      reorganization in cortical areas outside the temporal lobe. In addition, lesion
      studies indicate that, during infancy, visual recognition functions are widely
      distributed throughout many visual association areas but, with maturation, these
      functions become localized to area TE. Thus, the maintenance of exuberant
      projections together with reorganization in other cortical areas of the brain
      could account for the preservation of visual memories in monkeys that have had
      area TE removed in infancy.

PMID- 8748987
TI  - Evolution of spontaneous activity in the developing rat superior colliculus.
AB  - During the first 10 days after birth in the rat there are a succession of major
      developmental stages in the retinotectal pathway. During most of this time, the
      only recordable event in the superior colliculus is spontaneous activity. We
      studied and characterized this spontaneous activity, hypothesizing that it could
      play an important role in pathway development. The spontaneous discharges are
      detectable on postnatal day 5 (P5). After P5, the number of spontaneously active
      cells per penetration increases up to P10, after which they decrease to adult
      like levels by P14-P15. Between P5 and P10, the spontaneous discharges exhibit
      several patterns of activity, from constant firing to intermittent bursts with
      periods of quiescence, without any bearing to age. We isolated the retina and
      superior colliculus by injecting xylocaine onto the optic nerve and found no
      change in collicular activity. While this suggests that the spontaneous activity
      in the colliculus is independent of the retina at the ages studied, the opposite
      experiment, i.e., electrically stimulating the optic nerve, resulted in increased
      firing by collicular neurons, perhaps via nonclassical synaptic transmission.
      Finally, we compared interval histograms for spontaneously active cells between
      P5 and P15. The histograms suggest that at certain ages, spontaneous firing is
      more regular; moreover, these ages precede major functional advances, e.g., onset
      of numerous spontaneously firing cells at P6, the first response to optic nerve
      stimulation at P10, and the first light-evoked response at P12-P13. Our results
      support the hypothesis that spontaneous activity in the neonatal superior
      colliculus has a role in development of the retinotectal pathway, but the data
      also indicate that classical synaptic transmission is not involved.

PMID- 8748988
TI  - Physiological studies of visual cortex reorganization following cortical
      deafferentation in neonatal cats.
AB  - Whether restoration takes place in the visual cortex of neonates was
      physiologically studied in cortical cells of cats following their
      deafferentation. Deafferentation was performed by a parasagittal incision made in
      the visual cortex, separating the medial part of it from the thalamocortical and
      other visual fibers. Responsiveness (percentage of responsive cells) in the
      middle zone (the middle sector along the cortical incision) of the deafferented
      region was 82.5%, compared with 91.7% in the afferented (lateral to the incision)
      region (p = 0.5). In comparison, the responsiveness level was 32.3 and 81.3% (p <
      0.05) in the respective zones of the similarly deafferented adult controls. The
      ocular dominance distribution and binocularity were almost normal in the
      deafferented region of the neonatally operated cats, whereas binocularity was
      remarkably diminished in the adult controls. Recovery was also found in the
      specificity of the cells to orientation and direction in the neonatally operated
      cats, but not in the adult-operated cats. Thus, functional reorganization of the
      columnar organizations takes place in the neonatally deafferented but not in the
      adult-operated cats.

PMID- 8748989
TI  - Plasticity following neonatal visual cortex damage in cats.
AB  - We have used the cat visual system as a model system to investigate how remaining
      areas of the brain are able to take over functions that are lost following brain
      damage and why neonates show better behavioral recovery than adults. Anatomical
      studies with both anterograde and retrograde tracing methods reveal an increased
      projection from retina through thalamus to the posteromedial lateral suprasylvian
      (PMLS) extrastriate visual area of cortex in the damaged hemisphere of cats with
      a neonatal visual cortex (areas 17, 18, and 19; VC) lesion. No such enhanced
      projection is seen after an adult lesion. In addition, single-cell
      neurophysiological studies indicate that physiological compensation is present in
      PMLS cortex after a neonatal VC lesion but not after an adult lesion. The
      physiological compensation replaces (or maintains) properties that are
      characteristic of PMLS neurons; there is little or no improvement to replace the
      superior spatial properties of striate cortex (or areas 18 or 19) neurons that
      were lost. Immunohistochemical studies of the possible roles of neuronal growth
      factors in the compensation indicate that low- and high-affinity receptors are
      present that would allow several neurotrophins to influence the normal retina
      throughout life. Furthermore, these receptors are upregulated transneuronally
      following neonatal VC damage and thus could play a role in lesion-induced changes
      in the retina and its central projections. Ongoing studies are continuing to
      examine the presence of neurotrophins and their receptors in the retina and brain
      during normal development and after VC damage. In addition, studies of the
      effects of administering neuronal growth factors are underway to determine
      whether compensation for VC damage can be improved in neonates or even be
      produced in adults.

PMID- 8748990
TI  - Binocular interactions and visual acuity loss in esotropic cats.
AB  - Visual acuity was measured behaviorally in various groups of cats by using a two
      choice discrimination procedure. Cats in group 1 were rendered strabismic soon
      after birth by sectioning the tendon of the lateral rectus muscle (unilateral
      esotropia); at adulthood, their visual acuity (VA) was evaluated, after which the
      optic chiasm was sectioned and VA reassessed. Cats in group 2 were not only
      tenotomized but also chiasmatomized neonatally, while cats in group 3 underwent a
      neonatal section of the optic chiasm only. VA was measured at adulthood in the
      two latter groups. Group 4 consisted of adult cats whose VA was evaluated before
      and after an optic chiasm section. Stimuli consisted of square-wave gratings of
      various spatial frequencies. Results showed that in normal cats, the average
      threshold values under monocular viewing were identical for each eye (4.76
      cycles/degree); however, following optic chiasm section, monocular VA was reduced
      to 1.23 cycles/degree. VA in early optic chiasm section cats was lower than that
      of the normal cats but higher than that of late-lesioned animals (2.33
      cycles/degree). In strabismic cats, mean VA was 1.25 cycles/degree for the
      deviated eye and 2.8 cycles/degree for the normal eye. Following the optic chiasm
      section at adulthood, VA was lower not only for the deviated eye (< 0.17
      cycles/degree) but also for the normal eye (1.14 cycles/degree). Similar results
      were found when both the deviation and chiasmatomy were performed neonatally. The
      elimination of interocular interactions through chiasm transection failed to
      improve VA in the strabismic eye.

PMID- 8748991
TI  - Motives for having or not having children: a comparison between questionnaire and
      interview methods.
AB  - This study addresses validity issues in a questionnaire constructed with the aim
      of exploring a private and emotionally loaded topic, namely motives for having or
      not having children. Themes extracted by factor analysis of data from a reference
      population of men and women in the fertile ages were used to structure
      conversational interviews with a smaller sample of women and men of the same age.
      Of 30 persons invited, 24 agreed to participate in the interview and they
      completed the questionnaire before the interview. Factor scores were estimated
      from data obtained by means of the written questionnaire with closed questions,
      and the scores were compared with results from the structured interview with open
      questions. Thus, the questionnaire and the factor analysis were validated and a
      conclusion could be drawn that this method was able to provide important
      informatory facts even in an area where emotional factors are predominant. The
      findings also supported the idea that it is important to supplement questionnaire
      results with validity studies. The combination of the two methods in this study
      was fruitful and highlighted important new areas that need further research.

PMID- 8748992
TI  - Labor experience, maternal mood and cortisol and catecholamine levels in low-risk
      primiparous women.
AB  - This exploratory, prospective study was set up to determine the relationship
      between cortisol and catecholamine levels and labor experience and postpartum
      maternal mood. It was performed at the Coronation Hospital, which serves a low
      income urban population in Johannesburg. Blood samples were taken from 189 low
      risk primiparous women in active first stage of labor and analyzed for cortisol,
      norepinephrine, epinephrine and dopamine. The stress hormone levels were then
      correlated with maternal anxiety, depression and self-esteem scores, and changes
      associated with mothers' labor experience and pain. Patients who were distressed
      and required analgesia had higher cortisol levels. Those who described a more
      positive labor experience at 24 hours also had higher cortisol levels. There were
      no significant correlations between psychological test scores and stress hormone
      levels. Both labor pain at the time and a more positive recollected labor
      experience were associated with high cortisol levels. Cortisol and catecholamine
      levels in labor did not correlate with postpartum psychological test scores.

PMID- 8748993
TI  - Validation of the Edinburgh Postnatal Depression Scale (EPDS) in Chilean
      postpartum women.
AB  - A validity study of the Edinburgh Postnatal Depression Scale (EPDS) against the
      Research Diagnostic Criteria (RDC) was carried out on a sample of women attending
      a health care center in Santiago. One hundred and eight middle-class mothers
      filled in the EPDS and were later interviewed by the main author using the
      Psychiatric Assessment Schedule (PAS). The internal consistency of the EPDS was
      reasonably good (Cronbach's alpha 0.77). Validity coefficients for the scale were
      calculated to determine the best case/non-case threshold which was found to be
      9/10. Sensitivity, specificity and positive predictive value for this threshold
      were 100%, 80% and 37% correspondingly. The same best cut-off point (9/10) was
      found by other Chilean investigators in a sample of working-class women. The EPDS
      was shown to be a useful screening instrument for postnatal depression in these
      settings.

PMID- 8748994
TI  - Influence of marital relationship and child-care stress on maternal depression
      symptoms in the postpartum.
AB  - The predictive influence of two psychosocial factors (marital adjustment and
      child-care stress) on maternal depressive symptoms at 6, 9 and 12 months
      postpartum, was investigated. Seventy-one women from a sample of 202 primiparae
      from a larger study were included. The women were primarily educated, white,
      middle-class, married women in their early 30s who returned to work within the
      first postpartum year. Regression analyses indicated that the interaction of
      marital adjustment and child-care stress significantly influenced maternal
      depression symptoms at 9 months postpartum. The findings from this study support
      the necessity for following women beyond the early weeks and months of postpartum
      in subsequent research.

PMID- 8748995
TI  - Difficulties in the differential diagnosis of vaginismus, dyspareunia and mixed
      sexual pain disorder.
AB  - This retrospective study was undertaken to investigate predictors of vaginismus,
      dyspareunia and mixed sexual pain disorder in respect of symptom profile and
      treatment history variables of female patients and their partners. The study
      sample consisted of 147 female patients attending a university hospital
      outpatient clinic for Psychosomatic Gynecology and Sexology. All patients met the
      DSM-III-R criteria of the diagnoses of vaginismus (n = 50), dyspareunia (n = 46),
      or of both diagnoses (n = 51). No univariate differences were found between
      members of the three groups or between their partners. It was not possible to
      make a multivariate prediction of group membership.

PMID- 8748996
TI  - A preliminary investigation of what happens to women complaining of menorrhagia
      but whose complaint is not substantiated.
AB  - This observational follow-up study determined the outcome, after a minimum of 3
      years' follow up, in women complaining of excessively heavy menses, whose
      measured blood loss was within the normal range. Of the 81.7% of women followed
      up, 26% were happy with their periods, 19% were menopausal or taking hormone
      replacement therapy, 18% were taking a variety of other medical therapies and 28%
      had undergone surgery. The remainder were pregnant, lactating, or attempting
      conception. The decision to treat is not solely based on measured blood volume.
      Some women are intent upon an end to menstruation or have additional indications
      for surgical intervention. Others are happy with the reassuring knowledge that
      their menstrual blood loss is normal.

PMID- 8748997
TI  - Women's perceptions and experience of menopause: a focus group study.
AB  - Focus groups were used to investigate women's perception and experience of
      menopause, hormone replacement therapy, osteoporosis and doctor-patient
      relationships. Forty women aged between 45 and 55 years participated in seven
      focus groups. Most women thought that these topics were not widely or freely
      discussed in the community. Nevertheless they were able to share their
      experiences on this occasion. Lack of reliable, accessible and current
      information on menopause and related topics was identified as a problem. This was
      compounded by the contradictory nature of the information which was available.
      Hysterectomy and osteoporosis were identified as specific areas in which
      information was inadequate and not readily accessible. Solutions suggested by the
      women included distributing information pamphlets with contact numbers for
      further information to non-health-related settings such as hairdressing salons.
      The need to foster open discussion between women and their doctors was
      highlighted, with contributions required from both parties to develop a more
      equal partnership. A review of doctors' and women's surveillance practices with
      regard to hormone replacement therapy may also be warranted. We found focus
      groups a useful method for accessing women's experiences and perceptions. There
      was particular benefit in researchers being involved as moderators and scribes,
      and in an early post-focus group meeting to amplify and clarify records of the
      discussions. Small group size and an emphasis on confidentiality were, we
      believe, helpful strategies in encouraging discussion of intimate topics.

PMID- 8748998
TI  - Apolipoproteins: pathophysiology and clinical implications.

PMID- 8748999
TI  - Significance of apolipoproteins for structure, function, and classification of
      plasma lipoproteins.

PMID- 8749000
TI  - Quantitation of apolipoprotein B by chemical methods.

PMID- 8749001
TI  - Simultaneous quantification of apolipoproteins B-100, B-48, and E separated by
      SDS-PAGE.

PMID- 8749002
TI  - Apolipoprotein B-48.

PMID- 8749003
TI  - Chromatographic method for isolation and quantification of apolipoproteins B-100
      and B-48.

PMID- 8749004
TI  - Identification and characterization of truncated forms of apolipoprotein B in
      hypobetalipoproteinemia.

PMID- 8749005
TI  - Apolipoprotein B-48: problems related to quantification.

PMID- 8749006
TI  - Immunochemical separation of apolipoprotein B-48-and B-100-containing
      lipoproteins.

PMID- 8749007
TI  - Quantitation of apolipoprotein E.
AB  - Quantitation of apoE has proved to be extremely useful in studies of the
      regulation of apoE synthesis and metabolism. Measurement of serum apoE and/or its
      distribution among the lipoprotein classes may have clinical utility, although
      this remains to be established. Some of the unique properties of apoE such as its
      genetic, chemical, and structural heterogeneity, its propensity to self
      associate, and its ability to freely exchange on the surfaces of a wide variety
      of lipoprotein classes are factors that should be considered in measurements of
      apoE. The availability of commercial kits and reagents for human apoE
      quantitation make the development of apoE immunoassays readily achievable in most
      research and clinical laboratories.

PMID- 8749008
TI  - Quantification of apolipoprotein C-II by immunochemical and chromatographic
      methods.

PMID- 8749009
TI  - Immunochemical methods for quantification of human apolipoprotein C-III.

PMID- 8749010
TI  - Electrophoretic methods for quantitation of lipoprotein [a].

PMID- 8749011
TI  - Quantitation of lipoprotein (a) after lysine-sepharose chromatography and density
      gradient centrifugation.

PMID- 8749012
TI  - Two-dimensional nondenaturing electrophoresis of lipoproteins: applications to
      high-density lipoprotein speciation.
AB  - No single technique is able to separate each of the many HDL species present in
      native plasma. Some are present in only trace proportions. Some HDL have no
      obvious independent metabolic role, beyond perhaps serving as reservoirs of
      apoproteins active in metabolic events in other lipoproteins. The choice of HDL
      analytical technique depends mainly on the problem under study. Two-dimensional
      nondenaturing electrophoresis has been useful in studies of plasma cholesterol
      metabolism and cholesterol transport from cells, because it separates
      intermediates in these processes.

PMID- 8749013
TI  - Heterogeneity of high-density lipoproteins and apolipoprotein A-I as related to
      quantification of apolipoprotein A-I.

PMID- 8749014
TI  - Chromatographic methods for quantitation of apolipoprotein A-I.

PMID- 8749015
TI  - Purification, isoform characterization, and quantitation of human apolipoprotein
      A-IV.

PMID- 8749016
TI  - Immunochemical methods for quantification of apolipoprotein A-IV.
AB  - Several methods are available for the immunoassay of apoA-IV levels in plasma, or
      lipoproteins. The method of choice depends on the question being asked. If
      sensitivity is not a major determinant, simple immunoelectrophoresis is probably
      sufficient. To determine apoA-IV levels in plasma or lipoprotein fractions,
      either radioimmunoassay or a competitive ELISA is indicated. The competitive
      ELISA described above, however, offers sensitivity as well as rapidity and case
      of performance. When very low levels of apoA-IV are present (such as those
      produced by cultured cells), the higher sensitivity of the sandwich ELISA may be
      required.

PMID- 8749017
TI  - Quantitation of plasma apolipoprotein J.

PMID- 8749018
TI  - Human lipoprotein lipase: production in vitro, purification, and generation of
      polyclonal antibody.

PMID- 8749019
TI  - Immunochemical quantitation of lipoprotein lipase.

PMID- 8749020
TI  - Sandwich immunoassay for measurement of human hepatic lipase.

PMID- 8749021
TI  - Quantification of cholesteryl ester transfer protein: activity and immunochemical
      assay.

PMID- 8749022
TI  - Determination of apolipoprotein mRNA levels by ribonuclease protection assay.
AB  - The ribonuclease protection assay procedure described enables the relative
      quantitation of either single mRNAs or multiple mRNA species simultaneously in a
      sample of total RNA and demonstrates its applicability to two systems of
      relevance to the study of apolipoproteins, namely, liver tissue and liver-derived
      cell lines in culture. The main requirements of the method are the availability
      of cDNA cloned into a vector that directs the transcription of antisense RNA for
      the preparation of radioactive probes, and choice of suitable restriction
      endonuclease sites for linearizing the cDNA so that the final protected products
      of the various mRNA species are sufficiently different in size to allow their
      separation. For moderately abundant apolipoprotein mRNAs in rat liver, the method
      is sensitive down to 1 microgram total RNA. Other experimental sources of RNA or
      the assay of less abundant mRNA species may require a larger amount of starting
      material. These aspects of the assay need to be determined for each probe/ tissue
      system to be studied. The need for adjustments to the specific radioactivity of
      the probes will depend on the relative abundance of the target mRNA molecules and
      can be readily determined empirically. The rationale for varying the specific
      radioactivities to facilitate multiple assays as suggested here is both simple
      and effective. A preliminary assay provides information on the relative levels of
      the mRNA species of interest, and the step of preparing, in parallel, a sample of
      unlabeled antisense RNA provides the means for quantitative dilution of specific
      radioactivity of the 32P-labeled RNA probe where required.

PMID- 8749023
TI  - Psychostimulant-like effects of p-fluoroamphetamine in the rat.
AB  - The present study was undertaken to compare the pharmacological properties of p
      fluoroamphetamine with those of amphetamine and of other halogenated
      amphetamines, using several in vivo and in vitro tests. These included
      substitution testing in (+)-amphetamine (1 mg/kg, 5.4 mu mol/kg, i.p.)-, (+)-N
      methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine [(+)-MBDB] (1.75 mg/kg, 7.8 mu
      mol/kg, i.p.)-, and 5-methoxy-6-methyl-2-aminoindan (MMAI) (1.71 mg/kg, 8 mu
      mol/kg, i.p.)-trained rats, [3H]5-HT and [3H]dopamine uptake inhibition in whole
      brain synaptosomes, and changes in striatal extracellular levels of dopamine, 3,4
      dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) as measured by in
      vivo microdialysis in freely moving rats. In drug discrimination substitution
      tests, p-fluoroamphetamine fully mimicked (+)-amphetamine (ED50 0.43 mg/kg, 2.11
      mu mol/kg), whereas 'no substitution' was observed in rats trained to
      discriminate the serotonin (5-hydroxytryptamine, 5-HT)-releasing agents (+)-MBDB
      or MMAI from saline. p-Chloroamphetamine did not substitute for amphetamine but
      fully substituted for the (+)-MBDB and MMAI cues (ED50 0.17 mg/kg, 0.82 mu
      mol/kg, and 0.14 mg/kg, 0.69 mu mol/kg, respectively). p-Fluoroamphetamine, in
      comparison with p-chloroamphetamine and p-iodoamphetamine, showed much stronger
      inhibition of [3H]dopamine than [3H]5-HT uptake into rat brain synaptosomes but
      was less selective than amphetamine. p-Fluoroamphetamine (7.0 mg/kg, i.p.), 1 h
      after administration, strongly elevated (849% of baseline) extracellular dopamine
      in rat striatum measured using in vivo microdialysis. Amphetamine (2 mg/kg, i.p.)
      increased extracellular dopamine in rat striatum with a maximum at the same time
      as did p-fluoroamphetamine, but the latter gave a smaller increase. The data
      presented suggest that p-fluoroamphetamine resembles amphetamie more than it does
      the 5-HT-releasing type amphetamines.

PMID- 8749024
TI  - Adenosine A2 receptor-mediated modulation of contralateral rotation induced by
      metabotropic glutamate receptor activation.
AB  - Systemic pretreatment with the adenosine receptor antagonist theophylline
      significantly decreases contralateral rotation induced by unilateral
      intrastriatal 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD).
      Intrastriatal or intrasubthalamic nucleus coadministration of theophylline and
      1S,3R-ACPD significantly decreases contralateral rotation suggesting that
      metabotropic glutamate (mGlu) receptors and adenosine receptors interact locally.
      These appear to be adenosine A2 receptor effects as the adenosine A2 receptor
      antagonist 8-(3-chlorostyryl)caffeine (CSC) also decreases contralateral rotation
      induced by unilateral intrastriatal and intrasubthalamic nucleus administration
      of 1S,3R-ACPD, while the adenosine A1 receptor antagonist 8-cyclopentyl-1,3
      dipropylxanthine (DPCPX) has no effect. Pretreatment with the adenosine A2
      receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido
      adenosine hydrochloride (CGS 21680) potentiates contralateral rotation induced by
      unilateral striatal 1S,3R-ACPD, whereas pretreatment with the adenosine A1
      receptor agonist N6-cyclopentyl-adenosine (CPA) has no effect. These results
      suggest that mGlu receptor effects may be due, in part, to modulation of
      adenosine action.

PMID- 8749025
TI  - Effect of glibenclamide on ischemic canine myocardium with glucose infusion.
AB  - Glibenclamide, an ATP-sensitive K (K ATP) channel blocker, worsens the ischemia
      induced metabolic derangement in the heart through inhibition of K ATP channels.
      We examined whether the hypoglycemic effect of glibenclamide was involved in the
      worsening of myocardial energy metabolism during ischemia. Pentobarbital
      anesthetized dogs were subjected to 15-min ligation of the left anterior
      descending coronary artery. Either vehicle (dimethyl sulfoxide, DMSO) or
      glibenclamide (1 mg/kg) was injected i.v. 10 min before the ligation. In half of
      the animals given glibenclamide, glucose was continuously infused at 3 mg/kg per
      min immediately after glibenclamide injection. Glibenclamide increased the serum
      insulin level and decreased the blood glucose level. Glucose infusion completely
      abolished the hypoglycemia due to glibenclamide. Glibenclamide enhanced the
      decrease in ATP and total adenine nucleotides and increase in tissue lactate
      caused by ischemia. Glucose infusion did not cancel the augmentation of ischemia
      induced alterations of myocardial energy metabolism caused by glibenclamide.
      These results suggest that K ATP channels directly play an important role in
      endogenous mechanisms of myocardial protection against ischemic damage.

PMID- 8749026
TI  - Possible participation of histamine H3 receptors in the modulation of
      noradrenaline release from rat spinal cord slices.
AB  - Rat spinal cord slices prelabelled with [3H]noradrenaline were superfused with a
      medium containing 1 mu M desipramine plus 0.3 mu M phentolamine. Histamine (0.01
      10 mu M) and the selective histamine H3 receptor agonist R-(-)-alpha
      methylhistamine (0.001-10 mu M) caused a concentration-dependent decrease in the
      release of radioactivity evoked by electrical field stimulation (0.8 Hz, 20 mA, 2
      min). The inhibitory effect of histamine was not modified by either pyrilamine (1
      mu M) or ranitidine (10 mu M), but it was antagonized by burimamide (1 mu M). The
      inhibitory action of histamine (1 mu M) was attenuated by pertussis toxin (3 mu
      g/ml) and was abolished by N-ethylmaleimide (30 mu M). Neither forskolin (10 mu
      M) nor rolipram (100 mu M), nor the combination of both drugs, modified the
      inhibitory effect of histamine. Histamine (1 mu M) did not modify the overflow of
      tritium induced by electrical stimulation in the absence of phentolamine. The
      present results suggest that in the rat spinal cord the release of noradrenaline
      elicited by electrical stimulation is negatively modulated by histamine, probably
      through the activation of histamine H3 receptors. This modulatory mechanism is
      likely to involve the participation of regulatory Go/Gi proteins.

PMID- 8749027
TI  - The effect of the irreversible mu-opioid receptor antagonist clocinnamox on
      morphine potency, receptor binding and receptor mRNA.
AB  - In these experiments, the effect of the irreversible mu-opioid receptor
      antagonist clocinnamox on the potency of morphine, opioid receptor binding and mu
      opioid receptor mRNA was examined. Mice were injected with clocinnamox (0.32-12.8
      mg/kg) and the analgesic potency of morphine was examined 24 h later. Clocinnamox
      produced a dose-dependent decrease in the potency of morphine; and at the higher
      dose of clocinnamox the maximal analgesic effect was not observed following doses
      of morphine in excess of 500 mg/kg s.c. In saturation binding studies in brain,
      clocinnamox (0.32-25.6 mg/kg) dose-dependently decreased mu-opioid ([3H][D
      Ala2,MePhe4,Gly-ol5]enkephalin; DAMGO) receptor Bmax with relatively minimal
      effects on Kd. Binding to delta-opioid receptor ([3H][D-Pen2,D-Pen5]enkephalin;
      DPDPE) and kappa-opioid receptor ([3H](5,7,8)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)
      1-oxaspiro(4,5)dec -8-yl) benzeneacetamide; U69,593) was not affected by
      clocinnamox. The effect of clocinnamox was time-dependent in that the greatest
      changes in morphine potency and mu-opioid receptor density were observed within
      24 h of administration and decreased with time (336 h). Although mu-opioid
      receptor density was decreased to less than 30% of control 24 h following
      clocinnamox (12.8 mg/kg) and had increased to 80% by 5 days, a solution
      hybridization assay for mu-opioid receptor mRNA transcript revealed no changes in
      the steady-state levels of this mRNA. These studies indicate that clocinnamox is
      an irreversible antagonist at the mu-opioid receptor since it appears to
      selectively affect receptor density with minimal effects on affinity.
      Furthermore, clocinnamox produces time- and dose-dependent changes in Bmax and
      these changes appear to be unrelated to changes in mu-opioid receptor mRNA. It is
      possible that the repopulation of brain by mu-opioid receptors following
      clocinnamox is mediated by an existing pool of receptors that are activated
      following treatment.

PMID- 8749028
TI  - Cannabinomimetic behavioral effects of and adenylate cyclase inhibition by two
      new endogenous anandamides.
AB  - We have previously shown that the endogenous putative cannabinoid ligand
      arachidonylethanolamide (anandamide, 20:4, n - 6) induces in vivo and in vitro
      effects typical of a cannabinoid agonist. We now report that two other endogenous
      anandamides, docosatetraenylethanolamide (anandamide, 22:4, n - 6) and homo-gamma
      linolenylethanolamide (anandamide, 20:3, n - 6), have similar activities. The new
      anandamides bind to SV40-transformed African green monkey kidney cells
      transfected with the rat brain cannabinoid receptor cDNA and display K1 values of
      253.4 +/- 41.1 and 244.8 +/- 38.7, respectively. The value found for
      arachidonylethanolamide was 155.1 +/- 13.8 nM. In addition, the new anandamides
      inhibit prostaglandin E1-stimulated adenylate cyclase activity in Chinese hamster
      ovary-K1 cells transfected with the cannabinoid receptor, as well as in N18TG2
      mouse neuroblastoma cells that express the cannabinoid receptor naturally. The
      IC50 values for the inhibition of adenylate cyclase in transfected Chinese
      hamster ovary-K1 cells were 116.8 +/- 8.7 and 109.3 +/- 8.6 nM for
      docosatetraenylethanolamide and homo-gamma-linolenylethanolamide, respectively.
      These values were similar to that obtained with arachidonylethanolamide (100.5 +/
      7.7 nM), but were significantly higher than the IC50 value observed with the
      plant cannabinoid delta9-tetrahydrocannabinol (9.2 +/- 8.6 nM). The inhibitory
      effects of the anandamides on adenylate cyclase activity were blocked by
      pertussis toxin, indicating the involvement of pertussis toxin-sensitive GTP
      binding protein(s). In a tetrad of behavioral assays for cannabinoid-like
      effects, the two new anandamides exerted similar behavioral effects to those
      observed with delta9-tetrahydrocannabinol and arachidonylethanolamide: inhibition
      of motor activity in an open field, hypothermia, catalepsy on a ring, and
      analgesia on a hot plate.

PMID- 8749029
TI  - Different alpha1-adrenoceptor subtypes mediate contraction in rabbit aorta and
      urethra.
AB  - The alpha1-adrenoceptor subtypes mediating contraction of rabbit aorta and
      urethra were pharmacologically characterized using an isolated organ bath
      technique. Although aorta was as sensitive as urethra to the contractile action
      of methoxamine, phenylephrine was about 10 times more potent as a contractile
      agonist on aorta than on urethra. In aorta, the rank order of agonist sensitivity
      was norepinephrine > phenylephrine > clonidine > methoxamine whereas the rank
      order in urethra was clonidine > methoxamine > or = phenylephrine >
      norepinephrine. A lack of significant correlation between the potency of
      different alpha1-adrenoceptor antagonists tested against the phenylephrine
      induced contraction in aorta and in urethra indicated that different alpha1
      adrenoceptor subtypes mediated the contractile response in the two preparations.
      The potency of different alpha1-adrenoceptor antagonists tested in rabbit urethra
      was significantly correlated with their affinity for the cloned human alpha1c-,
      but not alpha1a- or alpha1b-, adrenoceptor subtype. Such a clear correlation with
      the potency of different alpha1-adrenoceptor antagonists tested in rabbit aorta
      and their affinity for one subtype of cloned human alpha1-adrenoceptor was not
      found. Chlorethylclonidine, which produced a 10 000-fold rightward shift in the
      phenylephrine concentration-response curve for rat aorta, had a weak inhibitory
      effect in rabbit aorta and urethra as well as in other rabbit tissues (spleen,
      fundus, renal artery, saphenous artery). The results indicate that significant
      heterogeneity exists among alpha1-adrenoceptor in rabbit aorta and urethra
      (alpha1c-adrenoceptor). However, chlorethylclonidine does not seem to be a
      suitable tool for the differentiation of alpha1-adrenoceptor subtypes in the
      rabbit.

PMID- 8749030
TI  - Responses to L-163,491, a nonpeptide angiotensin II mimic, in the pulmonary
      vascular bed of the cat.
AB  - Pulmonary vascular responses to 5,7-dimethyl-2-ethyl-3-[[2'
      [butyloxycarbonyl)amino-sulfonyl]-5'-(3-meth oxybenzyl)-[1,1'-biphenyl]-4
      yl]methyl]-3H-imidazo[4,5-b]pyridine (L-163,491), a novel nonpeptide angiotensin
      agonist, and angiotensin IV, the 3-8 amino acid fragment of angiotensin, were
      compared with responses to angiotensin II. Responses were investigated in the
      intact-chest cat under conditions of controlled blood flow and intralobar
      injections of angiotensin II, L-163,491, and angiotensin IV caused dose-related
      increases in lobar arterial pressure. When comparable in lobar arterial pressure
      of the three agents were examined, L-163,491 was approximately 3-fold less potent
      than angiotensin IV and approximately 100-fold less potent than angiotensin II
      when doses are expressed on a nmol basis. DuP 532, 2-propyl-4-pentafluoroethyl-1
      ([2'-(1H-tetrazol-5-yl)bipheny l-4]-methyl)imidazole-5-carboxylic acid, an
      angiotensin II AT1 receptor antagonist, reduced pulmonary vasoconstrictor
      responses to angiotensin II, angiotensin IV and L-163,491, but did not
      significantly change pressor responses to serotonin, norepinephrine, or the
      thromboxane A2 mimic, U46619. PD 123319, an angiotensin II subtype 2 receptor
      antagonist, did not significantly change pressor responses to L-163,491,
      angiotensin II, or angiotensin IV. Captopril, the angiotensin-converting enzyme
      inhibitor, decreased pulmonary vasoconstrictor responses to angiotensin I and
      enhanced vasodilator responses to bradykinin, but did not significantly change
      pressor responses to L-163,491. These data show that L-163,491 significant
      angiotensin AT1 receptor-mediated vasoconstrictor activity in the pulmonary
      vascular bed of the cat. These data also show the nonpeptide agonist has 3-fold
      less activity compared to angiotensin IV and is approximately 100-fold less
      potent than angiotensin II in the feline pulmonary vascular bed.

PMID- 8749031
TI  - Pretreatment with beta-endorphin facilitates the attenuation of delta-opioid
      receptor-mediated antinociception caused by delta-opioid receptor antisense
      oligodeoxynucleotide.
AB  - Intracerebroventricular (i.c.v.) pretreatment of male ICR mice with beta
      endorphin (0.6 nmol) or intrathecal (i.t.) pretreatment with antisense
      oligodeoxynucleotide to delta-opioid receptor mRNA (163 pmol) alone given 24 h
      earlier did not have any effect on i.t. administered delta-opioid receptor
      agonist [D-Ala2]deltorphin II (6.4 nmol)-induced antinociception. However, a
      concomitant i.c.v. pretreatments with beta-endorphin (0.08-0.6 nmol) and i.t.
      pretreatment with delta-opioid receptor antisense oligodeoxynucleotide (163 pmol)
      for 24 h dose-dependently attenuated i.t. challenged [D-Ala2]deltorphin II
      induced antinociception. A concomitant i.c.v. pretreatment with mu-opioid
      receptor agonist [D-Ala2,N MePhe4,Gly(ol)5]enkephalin (DAMGO) or kappa-opioid
      receptor agonist U50,488H and i.t. pretreatment with delta-opioid receptor
      antisense oligodeoxynucleotide for 24 h did not affect i.t. challenged [D
      Ala2]deltorphin II-induced antinociception. beta-Endorphin given supraspinally
      has been documented to release [Met5]enkephalin acting on delta-opioid receptors
      in the spinal cord. Our results indicate that supraspinal pretreatment with beta
      endorphin selectively causes a loss of spinal delta-opioid receptor-mediated
      antinociception in mice receiving delta-opioid receptor antisense
      oligodeoxynucleotide.

PMID- 8749032
TI  - Serotonergic modulation of cat bladder function before and after spinal
      transection.
AB  - Micturition was evoked in conscious cats by infusing saline into the bladder at a
      physiological rate. Drugs were administered intrathecally. Micturition volume
      threshold was increased by 5-hydroxytryptamine (5-HT, serotonin) and decreased by
      zatosetron, a 5-HT3 receptor antagonist, in spinally intact cats. Thus 5-HT3
      receptors inhibit micturition. After complete spinal transection, serotonin
      reduced volume threshold in 3 of 4 cats, indicating an alteration in serotonergic
      control. However, 2-methyl-5-HT, a 5-HT3 receptor agonist, increased volume
      threshold. Thus 5-HT3 receptor-mediated inhibition of bladder function remains
      after spinal transection. We conclude that some, but not all, serotonergic
      modulation of bladder function is altered after spinal transection.

PMID- 8749033
TI  - R(+)-8-OH-DPAT, a 5-HT1A receptor agonist, inhibits amphetamine-induced dopamine
      release in rat striatum and nucleus accumbens.
AB  - Systemic administration of R(+)-8-OH-DPAT (8-hydroxy-2-(di-n
      propylamino)tetralin), a selective serotonin (5-hydroxy-tryptamine, 5-HT)1A
      receptor agonist (25, 50, and 100 mu g/kg s.c.), administered 30 min prior to d
      amphetamine, significantly inhibited the d-amphetamine sulfate (1.0 mg/kg s.c.)
      induced increase in extracellular dopamine levels in the striatum and nucleus
      accumbens of freely moving rats, as determined by in vivo microdialysis. The
      ability of R(+)-8-OH-DPAT (50 mu g/kg s.c.) to inhibit d-amphetamine sulfate (1.0
      mg/kg s.c.)-induced increase in extracellular dopamine levels was abolished by
      WAY 100,635 (n-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-n-(2-pyridinyl)
      cyclohexanecarboxamide trihydrochloride), a selective 5-HT1A receptor antagonist
      (100 mu g/kg s.c.), administered 5 min prior to R(+)-8-OH-DPAT in both regions.
      These results indicate that the 5-HT1A receptor may exert an inhibitory effect on
      amphetamine-induced dopamine release.

PMID- 8749034
TI  - The (S)-enantiomer of 2-hydroxysaclofen is the active GABAB receptor antagonist
      in central and peripheral preparations.
AB  - In the guinea-pig isolated ileum, (RS)-(+/-)-baclofen induced a depression of
      cholinergic twitch contractions, reversibly and competitively antagonised by (S)
      2-hydroxysaclofen (pA2 = 5.2 +/- 0.2), but not by (R)-2-hyroxysaclofen. The
      depression of excitatory field potentials by baclofen ( 5 mu M) in rat CA1
      hippocampal slices was antagonised by (S)-2-hydroxysaclofen (100 mu m) (pA2 =
      4.3), whilst in rat neocortex, (S)-2-hyroxysaclofen (50-500 mu M) antagonised the
      baclofen (10 mu M)-induced suppression of spontaneous discharges, the (R)
      enantiomer being inactive. These results show that (S)-2-hydroxysaclofen is the
      active antagonist at central and peripheral GABAB receptors.

PMID- 8749035
TI  - Receptor occupation and pharmacokinetics of MPC-1304, a new Ca2+ channel
      antagonist, in spontaneously hypertensive rats.
AB  - MPC-1304, (+/-)-methyl 2-oxopropyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5
      pyridinedicarbonate , is a novel 1,4-dihydropyridine Ca2+ channel antagonist with
      potent and long-lasting antihypertensive effects. We characterized the ex vivo
      and in vivo binding properties of MPC-1304 to Ca2+ channel antagonist receptors
      in myocardial, aortic and brain tissues of spontaneously hypertensive rats (SHR)
      by radioreceptor assay using [3H](+)-PN 200-110 ([5-methyl-3H](+)-PN 200-110 (4
      (2,1,3-benzoxadiazol-4-yl)-1,4,-dihydro-5-methoxycarbonyl-2,6-d imethyl-1,4
      dihydro-3-isopropylcarbonylpyridine-5-carboxylic acid methyl ester)). At 1 and 6
      h after oral administration of MPC-1304 (10 mg/kg) in SHR, there was significant
      decrease (48%) in the number of [3H](+)-PN 200-110 binding sites (Bmax) in
      myocardial membranes compared to control values. The plasma concentration of MPC
      1304 in SHR correlated significantly with the occupation by this drug of
      myocardial Ca2+ channel antagonist receptors. The in vivo specific binding of
      [3H](+)-PN 200-110 in particulate fractions of aorta of SHR was significantly
      reduced (74.8 and 37.9%, respectively) at 1 and 6 after oral administration of
      MPC-1304 (3 mg/kg), while the myocardial [3H](+)-PN 200-110 binding was decreased
      only at 1 h later. In these rats, there was little change in cerebral cortical
      [3H](+)-PN 200-110 binding. In conclusion, MPC-1304 exerted more selective and
      sustained occupation in vivo of Ca2+ channel antagonist receptors in vascular
      tissues of SHR than in those of myocardial and brain tissues.

PMID- 8749036
TI  - Interactions of N-ethylmaleimide and aluminium fluoride with GABAB receptor
      function in rat neocortical slices.
AB  - Interactions of N-ethylmaleimide and aluminium fluoride (AlF - 4) with GABAB
      receptors have been examined using spontaneously discharging rat neocortical
      slices. The suppression of discharges by the GABAB receptor agonist baclofen (5
      10 mu M) was irreversibly prevented by N-ethylmaleimide (10-50 mu M) and its
      analog N-phenylmaleimide (10-50 mu M), whilst superfusion of slices with NaF (10
      mM) and AlCl3 (100 mu M) to form a fluoroaluminate (AlF - 4) complex markedly
      potentiated the action of baclofen. The lipoxygenase inhibitors,
      nordihydroguaiaretic acid (10-50 mu M) and eicosatetraynoic acid (10-50 mu M) or
      the phospholipase A2 inhibitor bromophenacylbromide (50-100 mu M) did not affect
      the response to baclofen. The depressant action of baclofen is evidently mediated
      through G-proteins, but is not dependent on arachidonic acid metabolites.

PMID- 8749037
TI  - Reversal of dizocilpine-induced disruption of prepulse inhibition of an acoustic
      startle response by the 5-HT2 receptor antagonist ketanserin.
AB  - Prepulse inhibition can be reliably disrupted by non-competitive NMDA receptor
      antagonists such as dizocilpine. In recent study, we found that the potent D2/5
      HT2 receptor antagonist, risperidone, but not the selective dopamine D2 receptor
      antagonist, raclopride, could reverse this disruption. The present study was
      therefore designed to examine the effect of the 5-HT2 receptor antagonist,
      ketanserin, against a dizocilpine-induced disruption of prepulse inhibition, as
      well as the behavioural stereotypy produced by this drug. Ketanserin (2 mg/kg)
      reversed the prepulse inhibition disruption produced by dizocilpine (0.15 mg/kg),
      as did the non-selective 5-HT1/5-HT2 receptor antagonist metergoline (1 mg/kg).
      Both drugs also attenuated some components of the behavioural stereotypy syndrome
      produced by dizocilpine (0.15 mg/kg). The present studies therefore suggest an
      interaction between 5-HT2 receptors and glutamatergic systems. This may be
      important for the antipsychotic profile of drugs having antagonist activity at 5
      HT2 receptors.

PMID- 8749038
TI  - K+ channel openers delay intestinal transit and have antidiarrheal activity.
AB  - The effect of pinacidil and cromakalim, two KATP channel openers, on intestinal
      transit and castor oil-induced diarrhea was studied in mice. Both drugs,
      administered orally, dose dependently inhibited the intestinal propulsion of
      charcoal, and castor oil-induced diarrhea, comparing favorably with morphine.
      These results may suggest a new approach for the symptomatic treatment of
      diarrhea.

PMID- 8749039
TI  - 7-Nitro indazole, an inhibitor of neuronal nitric oxide synthase, attenuates
      pilocarpine-induced seizures.
AB  - 7-Nitro indazole (25-100 mg/kg i.p.), an inhibitor of neuronal nitric oxide (NO)
      synthase, attenuated the severity of pilocarpine (300 mg/kg i.p.)-induced
      seizures in mice. This indicates that the decreased neuroexcitability of the
      central nervous system (CNS) following administration of 7-nitro indazole may be
      due to inhibition of neuronal NO synthase, implying that NO acts as an excitatory
      and proconvulsant factor in the CNS.

PMID- 8749040
TI  - Adenosine A2A receptor stimulation enhances striatal extracellular glutamate
      levels in rats.
AB  - The influence of CGS 21680, an adenosine A2A receptor agonist, on striatal
      glutamate extracellular levels was tested in a microdialysis study in rats. CGS
      21680 (10 mu M), infused intrastriatally through the microdialysis probe, greatly
      enhanced glutamate extracellular levels. These results show that striatal
      adenosine A2A receptors are involved in the regulation of striatal glutamate
      extracellular levels. They also suggest that adenosine A2A receptor antagonists
      may possess neuroprotective effects in models of striatal excitotoxicity.

PMID- 8749041
TI  - Corrigendum to 'the pentadecapeptide [Ser1]histogranin impairs passive avoidance
      learning in mice' [Eur. J. Pharmacol. 283 (1995) 251-254].
AB  - The peptides, histogranin and [Ser1]histogranin, were recently shown to modulate
      NMDA receptor function. In the present study, the effects of
      intracerebroventricular (i.c.v.) administration of [Ser1]histogranin and of the
      histogranin receptor antagonist, histogranin-(1-10), were examined on step-down
      type passive avoidance learning in mice. [Ser1]Histogranin (30-60 nmol) impaired
      retention, after post-training administration, but not when it was administered
      just prior to the retention assay. Histogranin-(1-10) (60 nmol) facilitated
      learning during training, without affecting retention. Co-administration of
      histogranin-(1-10) with [Ser1]histogranin (60 nmol each) led to a significant
      prevention of [Ser1]histogranin-induced learning impairment. These results
      indicate that [Ser1]histogranin impairs passive avoidance learning according to
      the pattern of NMDA receptor antagonists and involving specific histogranin
      sites.

PMID- 8749042
TI  - Enhancement by nifedipine of cholinergic-induced depression of locomotor activity
      in mice.
AB  - The dihydropyridine calcium channel blocker nifedipine did not affect spontaneous
      locomotor activity in mice when given alone but enhanced the depressant effects
      of the muscarinic receptor agonist oxotremorine and of the acetylcholinesterase
      inhibitor physostigmine. Such a behavioral depression might be due to neuronal
      changes induced by central calcium channel blockade combined with cholinergic
      activation. However, an involvement of hemodynamic factors, related to peripheral
      vasodilatation, cannot be excluded as locomotor depressant effects were also
      exerted by combinations of the two cholinomimetic agents with hydralazine, a non
      calcium antagonist vasodilator.

PMID- 8749043
TI  - Possible involvement of the L-arginine-nitric oxide pathway in the modulation of
      stress-induced analgesia.
AB  - The possible participation of nitric oxide (NO) in pain modulation and stress
      analgesia was studied in adult Wistar rats. Cerebral citruline as a coproduct of
      NO from L-arginine increased from the mean value 5.6 +/- 0.4 nM/mg.Pt. to 8.9 +/-
      0.5 nM/mg.Pt. in acute restraint stress. In high doses (50 mg/kg body weight),
      intraperitoneal administration of L-arginine caused a small and transient
      decrease of the tail-flick latencies to the thermal stimulus, without significant
      changes of the stress analgesia induced by restraint stress. In animals
      pretreated with N-nitro-L-arginine methyl ester (NAME) a progressive increase of
      the latency time was obtained and the increased latencies induced by acute
      immobilization appeared significantly potentiated. These results offer new
      indirect evidence in favour of the modulatory role of NO in thermoalgesic
      sensitivity and stress-induced analgesia.

PMID- 8749044
TI  - The effect of glucocorticoids on the activity of monoamine oxidase, copper-zinc
      superoxide dismutase and catalase in the rat hypothalamus.
AB  - The activities of biogenic amine deaminating enzymes, monoamine oxidase (MAO),
      types A and B, copper-zinc superoxide dismutase (CuZnSOD) and hydrogen peroxide
      (H2O2) scavenging enzyme, catalase, were studied in the hypothalamus of rats
      treated with dexamethasone (DEX) and corticosterone (CORT) for 2 and 7 days. Only
      chronic treatment (7 days) with both glucocorticoids (DEX -0.2 mg/kg b.w., i.p.
      and CORT -5 mg/kg b.w., i.p.) produced a significant decrease in hypothalamic MAO
      A and MAO-B activities. Under the same conditions DEX induced significant
      decrease in hypothalamic catalase and CORT in CuZnSOD activities. The results
      suggest that the effect of both glucocorticoids on MAO activities seems to be
      mediated by the same mechanisms, while this is not the case with antioxidant
      enzymes, catalase and CuZnSOD.

PMID- 8749045
TI  - Binding characteristics of glucocorticoid receptor in synaptic plasma membrane
      from rat brain.
AB  - The study was carried out to identify the specific glucocorticoid membrane
      binding site (GCMB) on synaptic plasma membrane (SPM), and to investigate the
      ligand binding properties and physico-chemical characteristics of GCMB. The
      radioligand binding assay showed that tritiated corticosterone ([3H]B) could bind
      to GCMB specifically with positive cooperativity. For SPM, the binding capacity
      (R(zero)) was 46.67 +/- 4.62 fmol/mg protein; the dissociation constant (Kd),
      97.48 +/- 18.85 nmol/L, and the Hill coefficient, 1.633 +/- 0.082. Various
      steroids bound with GCMB in the following rank order: RU26752, aldosterone >
      corticosterone, cortisol > RU26988, progesterone, R5020, triamcinolone acetonide
      > testosterone, estradiol > RU38486 > dexamethasone. GCMB, which could be
      solubilized by detergent Triton X-100, showed thermal stability, although it was
      susceptible to hydrolysis by trypsin and to the reducing agent, mercaptoethanol.
      The addition of divalent cations (Ca2+, Mg2+) was beneficial to the ligand
      binding. The results strongly indicate that GCMB, fulfilling the basic criteria
      for a receptor, constitutes a novel type of glucocorticoid receptor on neuronal
      membrane which is significantly different from the cytosolic glucocorticoid
      receptors.

PMID- 8749046
TI  - Physiological response in healthy subjects and in patients after myocardial
      infarction, elicited by a new computerised version of the Raven Coloured PM 47 as
      a mental stress test.
AB  - The Raven Progressive Matrices Test, in its various versions, has frequently been
      used in research on stress related diseases. In this paper the preliminary data
      relating to the administration of this version of test performed by a personal
      computer are presented. The "Coloured" version of the PM 47 was used, with the
      addition of a series of visual and acoustic stress stimuli; a maximum 30-second
      matrix presentation time was also introduced. Two groups took part in the test
      modified in this way: the first was made up of 23 male subjects aged 30 to 65 who
      had had a myocardial infarction in the previous six months; the second, a control
      group of the first, was composed of an equal number of subjects, without present
      or past cardiovascular or psychiatric disorders or illness. Frontal EMG, skin
      conductance response, peripheral temperature, heart rate and respiration rate
      were recorded at rest and during the test administration. The results obtained
      from the psychophysiological profile carried out on the two groups demonstrated
      the effectiveness of the methodology used in eliciting constant and stable stress
      responses.

PMID- 8749047
TI  - Motor rehabilitation: evolution of functional markers in trained hemiparetic
      patients and effectiveness of synchronous techniques.
AB  - The authors investigated, by means of isokinetic tests, a group of normotonic
      hemiparetic patients with the aim of showing the evolution, and in the short and
      medium term, functional markers of muscle strength and motor patterns. The
      results showed that the efficacy of the synchronous techniques used was good
      during the period of use. In the medium term, while the recovery of strength
      remained constant, the motor patterns deteriorated as co-contraction of
      antagonistic muscle groups restarted. This did not, however, lead to functional
      regression in comparison with the short term result (effectiveness).

PMID- 8749048
TI  - External ophthalmoplegia with ragged-red fibres and acetylcholine receptor
      antibodies.
AB  - The cases of two elderly women with external ophthalmoplegia, generalized muscle
      weakness and serum anti-acetylcholine receptor antibodies, are presented. The
      electophysiological studies showed a myopathic pattern but no indications of
      myasthenia after repetitive stimulation. The edrophonium test was negative and
      there was no response to anticholinesterase medication. In addition, elevated
      serum lactic acid levels and ragged-red muscle fibres in the muscle biopsy, were
      observed in both patients. These findings are discussed in relation to the fact
      that anti-acetylcholine receptor antibodies are diagnostic of myasthenia gravis,
      whereas ragged-red fibres and elevated lactic acid are correlated with
      mitochondrial myopathies.

PMID- 8749049
TI  - Molecular analysis and predictive testing in retinoblastoma.
AB  - Predictive testing using molecular analysis is an integral part of contemporary
      retinoblastoma management. We have made extensive use of segregation analysis for
      risk assessment in both familial and sporadic disease. Investigation of loss of
      heterozygosity in tumor samples proved to be invaluable for the identification of
      linkage phase. In many families, however, accurate carrier risk assessment
      depends on direct identification of the causative R B I mutation. Consequently,
      we have developed methods for rapid mutation screening. Using these techniques,
      mutation analysis can now be offered to an increasing number of individuals.

PMID- 8749050
TI  - Phenotype variations within a choroideremia family lacking the entire CHM gene.
AB  - A Swedish family with choroideremia and a deletion of the CHM gene has been
      studied with ophthalmological examination, full-field electroretinography, and
      DNA analysis in order to characterize the phenotype of the disease. Although all
      four patients studied had a complete deletion of the gene, they showed a
      considerable variability regarding the phenotype, including the electroretinogram
      tracings. Two of the affected males demonstrated a severe form of choroideremia
      with low or nondetectable ERG recordings, while the other two affected males
      showed a less severe phenotype with only a slight reduction of the ERG
      amplitudes. The variation of the clinical phenotype among family members carrying
      the same mutation indicates that the severity of choroideremia is not solely a
      function of the CHM gene.

PMID- 8749051
TI  - Ophthalmologic findings in Usher syndrome type 2A.
AB  - Thirty-seven patients, comprising 24 familial cases and 13 isolated patients with
      Usher syndrome type II (USH2), underwent ophthalmologic examination. Based on the
      degree of hearing loss, normal vestibular function, and gene-linkage analysis,
      familial cases were assumed to have USH2A. An analysis of genetic heterogeneity
      failed to reveal the presence of a second locus in the Dutch population. Although
      the patients appear to belong to a genetically homogeneous group, remarkable
      ophthalmologic variability was found. Corrected visual acuity decreased with age
      and remarkable differences in visual acuity were found within one family.
      Fundoscopic findings were classified as type A if attenuated vessels and bone
      corpuscles in all quadrants were found or as type B if findings other than these
      were found. The prevalence of type A significantly increased with age.

PMID- 8749052
TI  - Orbital rhabdomyosarcoma: treatment or overtreatment.
AB  - In 1972, the Intergroup Rhabdomyosarcoma Study standardized the classification
      and treatment of orbital rhabdomyosarcoma. It established chemotherapy with
      external beam radiotherapy as the standard of treatment, yet there was no
      comparison to treatment with external beam radiotherapy alone. We retrospectively
      examined the charts of patients with orbital rhabdomyosarcoma treated solely with
      external beam radiotherapy for the following data: age at diagnosis, gender,
      tumor recurrence, and tumor-related mortality. We followed 24 patients (mean
      follow-up 7.9 years) treated with external beam radiotherapy alone. The average
      age at diagnosis was 5.5 years; there were 15 males and 9 females. Three patients
      (12.5%) suffered tumor recurrence and there was one (4.2%) tumor-related death.
      When compared to the Intergroup Rhabdomyosarcoma Study, results suggest that
      chemotherapy with external beam radiotherapy may offer no advantage to external
      beam radiotherapy alone for the treatment of orbital rhabdomyosarcoma.

PMID- 8749053
TI  - A family with a syndrome of ectopia lentis, spontaneous filtering blebs, and
      craniofacial dysmorphism.
AB  - Six members of a family presented with a syndrome of mild facial dysmorphism,
      subluxation of the crystalline lenses, variable degrees of angle closure by
      iridocorneal adhesions, and patchy areas of iris atrophy. Three nonoperated eyes
      of two patients had spontaneous filtering blebs that presented as avascular
      cystic elevations of the superior conjunctiva. Systemic workup of all patients
      was negative for evidence of diseases known to be associated with dislocated
      lenses. The pedigree is most compatible with autosomal recessive inheritance with
      pseudodominance.

PMID- 8749054
TI  - Duane retraction syndrome associated with Rubinstein-Taybi syndrome.
AB  - The authors present a case report of Duane retraction syndrome (DRS) associated
      with Rubinstein-Taybi syndrome (RTS). RTS is a multisystem condition
      characterized by psychomotor developmental delay, broad thumbs and great toes,
      short stature, and characteristic facies with a beaked nose. DRS is an ocular
      disorder characterized by retraction of the globe with narrowing of the palpebral
      fissure in attempted adduction, with abduction and/or adduction deficiency, and,
      frequently, upshoot or downshoot of the affected eye on adduction. The case
      report described represents the first reported case of DRS associated with RTS,
      an association not previously recognized. This association raises the possibility
      that the abnormal CNS development in RTS may occasionally involve the ocular
      motor nerves.

PMID- 8749055
TI  - Macular dystrophy and hypotrichosis: the EEM-Albrectsen syndrome.

PMID- 8749056
TI  - Heavy ion effects in non-biological matter.
AB  - The effects of swift heavy ions in non-biological matter have been extensively
      studied during the last few years. Some results on non-biological solids are
      summarised here which might help to analyse comparatively the effects of high
      linear energy transfer (LET) particles in biological and non-biological matter.
      Special emphasis is put on the effects recently observed in organic solids. The
      experimental study of high-LET effects involves the use of accelerators and
      irradiation facilities. However, the requirements differ markedly from one study
      to the next, and ion accelerators of very different types have been used. A
      synthetic review of the existing sources and facilities is presented.

PMID- 8749057
TI  - Activation of thick targets by energetic heavy ions and the resultant radiation
      levels.
AB  - This study completes data collected for thick targets exposed to carbon and
      oxygen ions accelerated at 86 MeV/u. The radioactivity induced in carbon and
      tungsten targets bombarded by argon projectiles at 95 MeV/u has been studied in
      order to assess the relative contributions of the incoming heavy ion and the mass
      number of the bombarded nuclei to the consequent radiation hazards related to the
      production of radioactive ion beams. Induced radioactivity measurements are only
      rarely made under controlled irradiation conditions, in order to derive from the
      measured activities the dose rates after beam bombardment and a prediction of
      radiation protection constraints.

PMID- 8749058
TI  - Issues in protection from galactic cosmic rays.
AB  - Radiation risks to astronauts depend on the microscopic fluctuations of energy
      absorption events in specific tissues. These fluctuations depend not only on the
      space environment but also on the modifications of that environment by the
      shielding provided by structures surrounding the astronauts and the attenuation
      characteristics of the astronaut's body. The effects of attenuation within the
      shield and body depends on the tissue biological response to these microscopic
      fluctuations. In the absence of an accepted method for estimating astronaut risk,
      we examined the attenuation characteristics using conventional linear energy
      transfer (LET)-dependent quality factors (as one means of representing relative
      biological effectiveness, RBE) and a track-structure repair model to fit cell
      transformation (and inactivation) data in the C3H10 T1/2 mouse cell system
      obtained for various ion beams. Although the usual aluminum spacecraft shield is
      effective in reducing dose equivalent with increasing shield thickness, cell
      transformation rates are increased for thin aluminum shields. Clearly, the exact
      nature of the biological response to LET and track width is critical to
      evaluation of biological protection factors provided by a shield design. A
      significant fraction of biological injury results from the LET region above 100
      keV/mu m. Uncertainty in nuclear cross-sections results in a factor of 2-3 in the
      transmitted LET spectrum beyond depths of 15 g/cm2, but even greater uncertainty
      is due to the combined effects of uncertainty in biological response and nuclear
      parameters. Clearly, these uncertainties must be reduced before the shield design
      can be finalised.

PMID- 8749059
TI  - RBE for carcinogenesis following exposure to high LET radiation.
AB  - Stochastic radiation effects following exposure to heavy ions and other high
      linear energy transfer (LET) radiation in space are a matter of concern when the
      long-term consequences of space flights are considered. This paper is an overview
      of the relevant literature, emphasizing uncertainties entailed from estimates of
      relative biological effectiveness (RBE) for different experiment endpoints,
      making the choice of a single weighting factor for the prediction of cancer risk
      in man extremely difficult. Life-span-shortening studies in mice exposed to heavy
      ions and ongoing large-scale experiments in monkeys exposed to protons suggest
      that RBEs for all cancers are lower than 5. This does not exclude a much higher
      RBE for rare tumors such as brain tumors in monkeys or promoted Harderian gland
      tumours in mice at LET >80 keV/mu m. Skin cancer studies in rats exposed to neon
      or argon resulted in similar RBE. Exposure to fission neutrons led to high RBE in
      all species, not excluding values much higher than 20 for specific cancers such
      as lung tumors in mice and all cancers in rats. The estimate of maximal RBE is,
      however, extremely dependent on the hypothesis made on the shape of the dose
      response curves in the lower range of doses. These results suggest that neutrons
      may be the most hazardous component of high-LET radiation. There is only limited
      evidence from cancer experiments that LET >150 keV/mu m results in highly
      decreased efficiency, but this has been found for bone cancer induction following
      exposure to fission fragments.

PMID- 8749060
TI  - Radiation-induced carcinogenesis: individual sensitivity and genomic instability.
AB  - In spite of a well-known relationship between exposure to radiation and increased
      risk for cancer development, the biological mechanisms involved in radiation
      induced carcinogenesis remain poorly documented. Various hypotheses are discussed
      in this paper. It appears that radiation cannot be directly responsible for the
      numerous genetic alterations of cancer cells. Most of them occur during tumor
      progression. Only one or a very limited number of them was induced by radiation
      many years before tumor growth. This long delay is a major difficulty for
      experimental research and raises many questions. Recently, it has been shown that
      a genomic instability occurs after many generations in cells descending from
      irradiated cells. This instability leads to multiple genetic alterations and,
      preferentially, affects some chromosome structures, particularly telomeres. This
      kind of telomeric instability - related to the shortening of telomeric DNA
      sequences - has also been observed in senescent cells as well as in non-senescent
      cells from patients predisposed to cancer, and this process may possibly also
      occur in the progeny of irradiated cells.

PMID- 8749061
TI  - The proliferative capacity of mouse fibrosarcoma cells that survived x
      irradiation.
AB  - Delayed reproductive death, the appearance of colonies with a reduced cell
      density (impaired colonies) and the number of giant cells per colony were
      investigated in murine fibrosarcoma cells after irradiation with 3 to 9 Gy of x
      rays. Radiation survivors were replated after reaching confluence, which occurred
      after 13 to 15 doublings; this procedure was repeated three times. The replating
      efficiency decreased in a dose-dependent manner, the survivors of 9 Gy achieving
      only 30% of the plating efficiency of unirradiated cells. After the third
      replating, i.e. after 40 to 45 doublings, the plating efficiency of the survivors
      approached that of the controls. The median colony size of the survivors showed a
      similar dose-dependent decrease, which was pronounced after the first replating
      but still remained significant after the third replating. The fraction of
      impaired colonies was increased to more than 30% in 9-Gy survivors, and though
      abating, the increase was still significant even after the third replating.
      Evidence of residual damage was also provided by the presence of giant cells. For
      instance, after 6 Gy irradiation and 13 to 15 doublings, the proportion of
      colonies with giant cells was 60%, decreasing only to 45% after 40 to 45
      doublings. The number of giant cells per colony was 1.4 in colonies arising
      immediately after 6 Gy, decreasing to 0.9 after the third replating. These
      results suggest that the proliferative capacity of surviving cells is depressed
      even longer than their clonogenic capacity.

PMID- 8749062
TI  - The quality of DNA double-strand breaks: a Monte Carlo simulation of the end
      structure of strand breaks produced by protons and alpha particles.
AB  - The quality of DNA damage induced by protons and alpha-particles of various
      linear energy transfer (LET) was studied. The aim was to single out specific
      lesions in the DNA molecule that might lead to biological endpoints such as
      inactivation. A DNA model coupled with a track structure code (MOCA-15) were used
      to simulate the lesions induced on the two helixes. Four categories of DNA breaks
      were considered: single-strand breaks (ssb), blunt-ended double-strand breaks
      (dsb, with no or few overlapping bases), sticky-ended double-strand breaks (with
      cohesive free ends of many bases), and deletions (complex lesions which involve
      at least two dsb within a small number of base pairs). Calculations were carried
      out assuming various sets of parameters characterizing the production of these
      different DNA breaks. No large variations in the yields of ssb and blunt- or
      sticky-ended dsb were found in the LET range between 10 and 200 keV/mu m. On the
      other hand, the yield of deletions increases up to about 100 keV/mu m and seems
      to reach a plateau at higher LET values. In the LET interval from 30 to 60 keV/mu
      m, protons proved to be more efficient than alpha-particles in inducing
      deletions. The induction of these complex lesions is thus dependent not simply on
      LET but also on the characteristics of the track structure. Comparison with RBE
      values for cell killing shows that this special class of dsb might play an
      important role in radiation-induced cell inactivation.

PMID- 8749063
TI  - Effect of wire eccentricity on the performance of cylindrical proportional
      counters.
AB  - A theoretical and experimental investigation of the influence of eccentricity of
      the multiplication wire on the performance of cylindrical proportional counters
      is presented. The electric field in the counter is calculated by the method of
      images, and the Townsend formalism is used to derive the gas gain. The
      experimental determination of detector performance is carried out with 37Ar. The
      dependence of the gas gain and of the counter resolution on eccentricity is
      discussed, and it is shown that eccentricities up to 0.2 are of no concern in
      microdosimetric measurements with cylindrical proportional counters.

PMID- 8749064
TI  - Poly(ADP-ribosyl)ation as a fail-safe, transcription-independent, suicide
      mechanism in acutely DNA-damaged cells: a hypothesis.
AB  - Poly(ADP-ribose) polymerase (PARP, EC 2.4.2.30) is an abundant nuclear protein
      that is highly conserved and constitutively expressed in all higher eukaryotic
      cells investigated. Today, after about two decades of intensive research, we have
      a fairly comprehensive picture of its remarkable enzymatic functions and of its
      molecular structure. Its physiological role, however, remains controversial. The
      present hypothesis attempts to reconcile the different findings. By extending an
      earlier hypothesis, it is proposed that poly(ADP-ribosyl)ation is primarily a
      mechanism to prevent survival of mutated, possibly apoptosis-incompetent, cells
      after acute DNA-damage. Recent reviews on PARP may be found in [1-4].

PMID- 8749065
TI  - Vestibular evoked myogenic potentials in the sternomastoid muscle are not of
      lateral canal origin.
AB  - We studied vestibular evoked myogenic potentials in 6 patients after unilateral
      vestibular neurectomy and in 22 patients after unilateral vestibular neuritis and
      unilateral absent caloric responses. We found that the ipsilesional vestibular
      evoked potentials were abolished in every patient after unilateral vestibular
      neurectomy. In vestibular neuritis patients we found that the ipsilesional
      vestibular evoked potentials were absent in some but not in all cases. These
      findings confirm that the p13-n23 potential is of vestibular origin and also show
      that it is not of lateral canal origin.

PMID- 8749066
TI  - Evaluation of the human vestibulo-ocular reflex at high frequencies with a
      helmet, driven by reactive torque.
AB  - A new technique was developed to test the VOR in humans. A tightly but
      comfortably fitting helmet was provided with an electronically controlled torque
      motor that rotated a mass around a vertical axis. Acceleration of the motor
      caused reactive torque of the helmet in the opposite direction which was
      transmitted to the (freely movable) head. Sinusoidal head oscillations in the
      frequency range 2-20 Hz (peak-to-peak amplitudes about 10 degrees and 0.1 degrees
      respectively) were easily achieved, as well as step displacements of the head
      with accelerations on the order of 1000 degrees/s2. Limitation of the maximum
      torque and lack of any rigid attachment of the head to a fixed structure made the
      technique safe and comfortable. Eye and head rotations were recorded,
      independently of head translations, with eye and head search coils in a
      homogeneous a.c. magnetic field. In normal subjects, gain was near unity at 2 Hz:
      above 8 Hz, gain increased progressively toward 1.1-1.3 at 20 Hz. Phase lag
      increased from a few degrees at 2 Hz to about 45 degrees at 20 Hz. Above 2 Hz,
      these results were unaffected by visual conditions; lower gains and increased
      phase lags were found in subjects with bilateral or unilateral vestibular loss.
      For step displacements, gain (measured in the first 100 ms) was near unity for
      normals, near zero after bilateral vestibular loss and strongly asymmetrical
      after unilateral vestibular loss. Thus, the technique seems highly effective in
      testing vestibular function with minimal contamination by other systems.

PMID- 8749067
TI  - Real time binocular detection of horizontal vertical and torsional eye movements
      by an infra red video-eye tracker.
AB  - So far it has only been possible to detect horizontal and vertical eye movements
      during real time; torsional eye movements have to be calculated from video-tape
      that have been processed several times, and each investigation takes considerable
      time. We developed a real time binocular infra red video eye tracker for routine
      clinical examination which allows real time graphical visualization of
      horizontal, vertical and torsional eye movements with a bandwidth of 12 Hz (25 Hz
      refresh frequency). Eye movements in three dimensions can now be obtained as easy
      as has been done before with electronystagmography for the horizontal component.
      In contrast to previous systems described, we analyze only those parts of the
      video-frame that are essential for detection of all three eye movements. This
      results in a huge data-reduction accompanied by a speed-up of analysis. The black
      pupil centre is detected by an iterative process of analyzing several horizontal
      and vertical lines of the even video field. The algorithm searches for regions of
      minimal intensity. Horizontal and vertical eye rotation is then calculated and
      transformed into Fick's coordinates. Based upon the centre of the pupil four
      concentric segments are defined in the iris to detect torsion and to enable
      correction for false rotation. Torsion is detected by cross-correlation of each
      segment and estimated from the outcome of the correlation coefficients. All
      transformations are established by predefined stored transformation matrices thus
      making real time calculations for transformation unnecessary. After corrections
      for eccentricity and assuming that fixation of the subjects tested was perfect,
      accuracy appears to be within 0.3 degrees-1.0 degrees for all three dimensions.
      Linearity after all corrections is within 4-9% within a visual field of 60 x 40
      degrees (horizontal x vertical).

PMID- 8749068
TI  - High frequency deficit of the vestibular system after acoustic neurinoma surgery.

PMID- 8749069
TI  - Postural control in Meniere's disease and acoustic neurinoma when studied on a
      linearly oscillating platform.
AB  - We investigated the effect of visual control on postural stability on a moving
      platform in 36 patients with Meniere's disease (MD) in 25 patients with operated
      acoustic neurinoma (AN) and in 19 healthy controls. The force platform was placed
      on rails and oscillated linearly at frequencies from 0.2 to 5 Hz at a constant
      velocity of 30 mm/s. In all subjects, the support surface oscillation produced
      postural instability that differed significantly from the base line stability.
      The body sway velocity increased almost linearly with the increase of stimulation
      frequency. The MD patients swayed more than the AN patients at base line
      measurements in non-visual conditions but not during platform movement. In visual
      conditions the AN patients stabilized their posture significantly better than the
      MD patients, who showed deteriorating visual control of posture during platform
      movement. The controls differed from the patients in all test conditions except 5
      Hz stimulation, which causes the body segment to fall into resonance. The Romberg
      quotients (RQ) in MD patients was significantly poorer during platform movement
      than in controls, except at 5 Hz stimulation. The AN patients had higher RQ
      values than controls, and mainly used vision to compensate their vestibular
      deficit. Thus, patients with MD fail to control their posture efficiently with
      vision during movement which may explain the visually induced dizziness in MD
      patients.

PMID- 8749070
TI  - Predictable and pseudo random saccades in patients with acoustic neuroma.
AB  - We studied predictive and pseudo random saccades in patients with
      cerebellopontine angle tumor. Target for the saccades was a laser beam which was
      reflected on the wall in front of the subject, and the stimulus was controlled by
      a computer. The fixed target was spaced at a distance of +/- 30 to each side of
      the subject. The random saccades jumped 20 degrees/40 degrees/60 degrees in an
      unpredictable manner. The saccade analysis program was based on pattern
      recognition. In the random saccade test none of the mean values of saccadic
      reaction time (SRT), saccadic accuracy (SA) and saccadic peak velocity (SPV) to
      the right or left differed significantly between the two groups. In the
      predictable saccade test there was statistically significant differences for
      certain variables: in right SRT (p < 0.01) and in left SRT (p < 0.01); in right
      SA (0.001 < p < 0.01) and in left SA (p < 0.001). The mean peak velocity (right
      SPV and left SPV) did not differ significantly between the two groups. When the
      stimulus is predictable, the saccades in a healthy subject are more timely spaced
      and accurate than in a patient. When the stimulus is unpredictable, "the memory
      of the past" has no importance and cannot help in saccade programming, and
      variability in the healthy subjects increases.

PMID- 8749071
TI  - Culturing of acoustic neuroma--methodological aspects.
AB  - We have been able to culture acoustic neuroma (AN) tissues by taking small tumor
      pieces during surgery from the cisternal or, preferably, metal part of the tumor
      where macroscopic tissue degeneration is not prominent. The AN pieces were
      transported in culture tubes to our cell laboratory where they were sliced and
      transferred to culture medium. The AN tissue demands a crude culture suspension
      containing laminin. We have been successful in culturing 15 successive ANs. The
      cells have different morphological features with characteristics of type Anthony
      A and B. Four main cell types were recognized: ameboid microglia-like cells,
      spindle-shaped cells, racket-shaped cells, and kite-shaped cells. However, no
      immortal cell line could be established. Some of the cultures were viable for up
      to 4 months.

PMID- 8749072
TI  - Discrimination of patients with acoustic neuroma and peripheral vestibular
      lesions with human posture dynamics.
AB  - A group of normal subjects (n = 17) was compared with groups of patients with a
      diagnosis of vestibular neuritis (n = 18), and acoustic neuromas (n = 35). Fisher
      linear discriminant analysis was applied to distinguish clusters of parameters
      characteristic for each disease. Hence it was possible to distinguish the
      vestibular neuritis patients from the normal group with statistical significance
      (p < 0.01). Also the patients with an acoustic neuroma could be distinguished
      from the normal subjects with statistical significance (p < 0.05).

PMID- 8749073
TI  - Facial nerve involvement in patients with acoustic neurinomas. Examination with
      magnetic single- and bi-stimulation.
AB  - The diagnosis of acoustic neurinomas is usually made by auditory and vestibular
      testing and magnetic resonance imaging. As clinical involvement of the facial
      nerve is infrequent, occurring only in large tumours, only little is known about
      the subclinical involvement of the facial nerve. Transcranial magnetic
      stimulation of the VIIth cranial nerve in the temporal bone, adjacent to acoustic
      neurinoma growth, seems to be an adequate instrument for electrophysiological
      measurements of minimal nerve lesions without clinically obvious facial palsy. In
      70% out of 97 patients with surgically and histologically confirmed acoustic
      neurinomas, obvious elongation of the intratemporal conduction time of the facial
      nerve was found. This affection was dependent on tumour size. No correlation was
      found to preoperative or postoperative facial nerve function and hearing
      function. The latencies of the conduction time showed a tendential increase in
      patients with a more difficult grade of surgery and of facial nerve preparation
      due to fibrous adhesions and nerve spreading on the tumour capsule. A completely
      new stimulation modality, the application of two magnetic stimuli in quick
      succession, was applied for the first time in acoustic neurinoma patients, and
      revealed facial nerve involvement by acoustic neurinoma growth. Facial nerve
      involvement in acoustic neurinoma can be detected by transcranial magnetic
      stimulation even in patients with small and medium sized tumours but with
      clinically normal facial function.

PMID- 8749074
TI  - Influence of low dose alcohol on fixation suppression.
AB  - The decrease of fixation suppression after small doses of alcohol was studied in
      40 healthy volunteers (20 male, 20 female) using rotatory stimulation. 0.5 g
      alcohol per kg body weight were given within 20 min. The maximum fixation
      suppression and blood alcohol concentrations (BAC) were measured before and at
      15, 30, 45, 60, 120, 180 and 240 min after ingestion. We determined the maximum
      angular acceleration during which total suppression of the vestibulo-ocular
      reflex (VOR) was still possible. Fixation suppression was successful up to mean
      values of 43.6 degrees/S2 before ingestion of alcohol (reference level). A first
      significant deterioration of fixation suppression was observed at BAC of 20
      mg/100 ml decreasing constantly with increasing BAC. At the median maximum BAC of
      65 mg/100 ml, fixation suppression was possible up to acceleration values of 20%
      compared with reference levels. Measuring of the maximum fixation suppression in
      rotational tests is a reproducible easy method to describe the central nervous
      system control of vestibular functions. This method shows impressingly the
      enormous effects of low doses of alcohol on equilibrium. It is concluded that at
      BAC of more than 50 mg/100 ml a remaining vestibular nystagmus might be observed
      when driving a bend.

PMID- 8749075
TI  - Linear acceleration perception: frequency dependence of the hilltop illusion.
AB  - Periodical stimulation of the otoliths during linear horizontal displacement
      leads not only to motion and displacement perception but also to the "Hilltop
      Illusion", which is the perception of being transported not on an earth
      horizontal path, but over a small hill. This phenomenon is explained by the
      partial reinterpretation of the linear acceleration to a tilt of the
      gravitational vertical. The dynamics of the illusion and its role in the
      perception of spatial orientation were investigated for eight frequencies. The
      subjects were exposed to sinusoidal linear acceleration and had to dynamically
      adjust a luminous line display to their subjective vertical. This served as a
      quantitative indicator of the amount of perceived tilt with respect to gravity.
      The high frequency part (0.1-0.33 Hz) of the experiment was performed on a
      conventional linear acceleration device (sled), the low frequency part (0.0083
      0.05 Hz) on the sled centrifuge (a rotating sled). The amplitude ratio of the
      settings of the subjective vertical was found to be similar to that of a lowpass
      with a 15 s time constant. However, the phase shifts never exceeded a 40 lag,
      which together with other experimental results led to the conclusion that a non
      linear, possibly predictive type of information processing must be at work.

PMID- 8749076
TI  - Otolithic thresholds influence the perception of passive linear displacement.
AB  - The vestibular sensors are the necessary source of information for estimating
      self-displacement during passive linear transport. Displacement has to be
      computed from the otolith signal by means of an integration process (path
      integration), which provides a measure of linear acceleration. However, the onset
      of self-motion perception is delayed due to perceptual thresholds. We
      investigated the effect of these thresholds on the estimation of passive
      displacement. Subjects seated on a linear acceleration device (ESA-SLED) were
      displaced to their left or right. Two tasks were performed: (1) subjects pressed
      a button when they perceived self-motion; (2) subjects pressed a button when they
      thought they had reached a previously seen visual target located above the sled
      rail. Displacement estimation (task 2) was found to depend upon the acceleration
      magnitude and on the individual motion perception threshold measured in task 1.
      The results can be explained by assuming that self-displacement computation
      starts at the onset of self-motion perception and is initialised by a value that
      is independent of the amplitude of acceleration, thereby compensating for the
      displacement information lost due to the thresholds.

PMID- 8749077
TI  - The visual vertigo syndrome.
AB  - Neuro-otological and posturography findings in 15 patients with visually induced
      vertiginous symptoms (visual vertigo, VV) are reported. Most patients were
      considered to have peripheral vestibular disorders but one had cerebellar
      degeneration and another a brainstem stroke. Five patients showed abnormally
      large body sway induced by full-field visual motion stimulation; including the 2
      patients with CNS disease. Four of these 5 patients had additional strabismic
      symptoms (diplopia, squint surgery and ocular muscle weakness). VV may occur if
      patients with balance disorders show high visual field dependence. The presence
      of additional CNS or strabismic symptoms, probably by reducing the ability to
      resolve conflicting visual stimuli, may lead to inappropriate postural reactions.

PMID- 8749078
TI  - Hyperactive VOR and hyperventilation after whiplash injury.
AB  - Otoneurological and respiratory tests were performed on 32 patients after
      whiplash injury caused by a rear-end car collision. Oculomotor and cervico-ocular
      test results were generally normal. In a significantly large number of case, the
      vestibulo-ocular reflex (VOR) was hyperactive (n = 17; 53%) and the respiratory
      test results were typical of the hyperventilation syndrome (HVS) (n = 12; 38%).
      Hyperactive VOR and the HVS occurred significantly more often in combination (n =
      7; 22%) than could be accounted for by combined false positivity. Most of the
      significant findings were due to high relative frequencies in the women. The
      hyperactive VOR might have been the result of plastic adaptation to limited head
      mobility secondary to neck pain. Behavioural and emotional distress might offer
      alternative explanations for both the hyperactive VOR and HVS.

PMID- 8749079
TI  - Neurootological contributions to the diagnostic follow-up after whiplash
      injuries.
AB  - Only in 1992 we had to deal with about 197,731 cases of whiplash injuries due to
      traffic accidents on the roads of Germany. About 80% recover within a few months.
      However, about 15%-20% develop the so-called late whiplash injury syndrome with
      many complaints of the cervico-encaphalic syndrome including headache, vertigo,
      instability, nausea, tinnitus, hearing loss etc. The orthopedic as well as the
      radiological findings are mostly unsatisfactory with respect to the
      neurosensorial complaints. Therefore problems of evidence arise in compensation
      claims calling for additional neurootological medical expertise. When analysing
      124 expert examinations of our patients suffering from late whiplash injury
      syndrome we found that the average case had already seen 3.83 medical experts
      elsewhere including 18 different medical specialities. At the most, we observed
      17 expertise visits/case prior to the patients visit to us. In the present study
      we compared the results from 42 neurootological expertise cases with 206 cases of
      late whiplash injury syndrome, who only came for treatment purposes to our
      neurootological practice. Al our patients underwent a systematic history (NOASC
      I) and a functional neurootological, audiometric and equilibriometric
      examination. Thus we tried to assess the location and nature of the functional
      degeneration underlying the posttraumatic residual vertigo symptoms, etc. The
      objective and quantitative equilibrium investigations included several ENGs and
      an analysis of the cranio-corpo-gram, thus obtaining a record of the gait and
      standing patterns by means of a radar-like image of the marker tracings from the
      head and the shoulders during stepping and standing, as well as during bending,
      extending and turning the neck (computer CCG). Thus individual patterns of
      functional lesions in the neurootological pathways can simultaneously?
      objectively and quantatively be worked out for both the groups confirming the
      subjective complaints.

PMID- 8749080
TI  - "Dumping" of activity within the VOR is possible after unilateral vestibular
      neurectomy.
AB  - The effect of head tilt on postrotatory nystagmus was studied in patients at long
      time follow-up of complete unilateral vestibular lesions. Ten patients were
      tested 2-4 years after unilateral vestibular neurectomy. They were all found to
      have short VOR time constants. However, at postrotatory head tilt the VOR time
      constant was further shortened. This suggests that the velocity storage
      mechanisms may function even in cases with complete unilateral vestibular
      lesions.

PMID- 8749081
TI  - Unilateral vestibular deafferentation (UVD) causes permanent asymmetry in the
      gain of the yaw VOR to high acceleration head impulses in guinea pigs.
AB  - Using an acute scleral search coil technique for measuring eye position in alert
      animals we have shown that after UVD the yaw VOR in the guinea pig shows a
      permanent gain asymmetry. There is a reduced gain during the first 100 ms of
      brief, high acceleration horizontal head rotations ("yaw head impulses") towards
      the operated side, but only a small loss in gain for similar rotations towards
      the intact side. This result confirms that the horizontal E response during the
      first 100 ms of an abrupt high acceleration head rotation is a clear indicator of
      the function of the horizontal canal. These results are similar to those in human
      patients after unilateral acoustic neuroma operations. The asymmetry in response
      is large shortly after UVD and decreases over time but is permanent.

PMID- 8749082
TI  - Torsional eye velocity components during yaw angular acceleration identify the
      side of unilateral vestibular deafferentation.
AB  - Using dual torsion scleral search coils we have recorded 3-dimensional eye
      position during yaw angular accelerations of 20 degrees/s2 about an earth
      vertical axis in healthy subjects and in patients with unilateral vestibular
      deafferentation (UVD). These experiments produced two interesting results: i)
      even in healthy subjects, the axis of eye velocity did not coincide with the
      (earth vertical) stimulus axis during centred rotation; ii) Patients with UVD had
      torsional eye velocity components that were systematically different from those
      in normal subjects. While in normals the direction of the torsional component of
      the eye velocity depended on the direction of rotation and was on average
      approximately symmetric for CW and CCW yaw rotation, there was a clear asymmetry
      in patients, which was distinctly different for left and right UVD.

PMID- 8749083
TI  - Influence of target distance and acceleration level on eye movements evoked by
      lateral acceleration steps.
AB  - Lateral eye movements produced by linear acceleration along the inter-aural axis
      were studied in 6 normal subjects. They were seated upright, whole-body
      restrained, and were exposed to randomised rightward/leftward steps of 0.05 g.
      0.1 g, 0.24 g of 600 ms duration. When viewing earth-fixed targets at 30, 60 or
      280 cm from their eyes, mainly pure compensatory slow-phase eye movements were
      evoked at latencies around 50 ms measured for the closest viewing distances. At
      onset, slow-phase amplitude was modulated by acceleration and target distance.
      When the subjects were stationary and pursued moving targets at similar distances
      and accelerations, latencies around 140 ms were observed, and catch-up saccades
      were frequently made. From these experiments, we defined the dynamics of the
      otolith-ocular reflex for various levels of acceleration and viewing distances.

PMID- 8749084
TI  - Subjective postural vertical in peripheral and central vestibular disorders.
AB  - The perception of subjective postural vertical was assessed in normals and
      patients with peripheral and central vestibular disorders and spasmodic
      torticollis. The subjects were seated in a motorized gimbal with the head and
      torso restrained and their eyes closed. The gimbal executed 7-10 cycles of tilt
      around the vertical at 1.5 degrees/s in either pitch or roll. Subjects indicated
      when they began to feel upright and again when they began to feel tilted by an
      analogous 3-position joystick. Normal subjects felt upright within a sector of 5
      6 degrees around vertical in pitch and roll. Five patients with absent vestibular
      function, 25 torticollis patients and 3 patients with acute unilateral peripheral
      vestibular lesions showed a significant increase of the sector in pitch and roll,
      but only the latter had a mild directional bias. Two patients with long standing
      complete unilateral vestibular deficit and 8 patients with up or downbeat
      nystagmus in the vicinity of upright had abnormally large sectors within which
      they felt to be upright. The results suggest that vestibular function is
      important for the accurate perception of the postural vertical and that a
      directional asymmetry in vestibulo-ocular function or a head tilt does not
      necessarily correlate with a directional bias of subjective verticality.

PMID- 8749085
TI  - Effect of vergence on the gain of the linear vestibulo-ocular reflex.
AB  - We measured the linear vestibulo-ocular reflex (LVOR) and vergence, using
      binocular search coils, in 3 humans. The subjects were accelerated sinusoidally
      at 0.5 Hz and 0.2 g peak acceleration, in complete darkness, while performing
      three different tasks: i) mental arithmetic; ii) tracking a remembered target at
      either 0.34 m or 0.14 m distance; and iii) maintaining vergence at either of
      these distances by means of audio biofeedback based on vergence. Subjects could
      control vergence using the audio feedback; there was greater convergence with the
      near audio target. However, there was no significant difference in vergence
      between the near and far remembered target conditions. With audio feedback, the
      amplitude of smooth tracking was not consistently different for the near and the
      far conditions. However, the amplitude of tracking (saccades and smooth
      component) in the remembered target conditions was greater for near than for far
      targets. These results suggest that linear VOR amplitude is not determined by
      vergence alone.

PMID- 8749086
TI  - Influence of gravity on the orientation of vestibular induced quick phases.
AB  - In rabbits and cats the orientation of the quick phases (QPs) of the vestibulo
      ocular reflex (VOR) was studied varying the head position in space. At different
      head tilt positions, QPs induced by step vestibular stimulation disaligned with
      respect to the stimulus toward the orientation of the earth's horizontal axis.
      The rabbits' QPs were horizontal during yaw stimulation and remained horizontal
      in a range of head pitch of +/- 90 degrees (reorientation gain = 1). Therefore,
      the slow compensatory responses (CSPs) progressively disaligned compared with the
      QPs. QPs induced by roll stimulation also showed horizontal orientation, although
      these were rare in the upright position and occurred more frequently when the
      head was pitched. In cats only the yaw-induced QPs were coplanar with the
      stimulus, while QPs induced by pitching were mostly oblique. It followed that in
      either yawing or pitching, the QPs had their end point scattered within a
      horizontally elongated area of the visual field. When tilting cats in the frontal
      plane, the orientation of QP trajectories changed with respect to the stimulus so
      that the end point distribution tended to remain aligned toward the horizontal
      instead of being fixed in the orbit. The reorientation gain decreased from 1 to
      0.5 by increasing the head tilt. On the basis of difference regarding eye
      implantation and motility it was suggested that the effect of gravity on the
      orientation of QPs could be aimed at maintaining the interocular axis aligned
      with the horizon in the rabbit and at orientating the visual scanning system in
      the horizontal plane in the cat.

PMID- 8749087
TI  - Role of the spinocerebellum in adaptive gain control of cat's vestibulospinal
      reflex.
AB  - In decerebrate cats, a 3-h period of sustained roll tilt of the head (at 0.15 Hz.
      +/- 10) leading to selective stimulation of labyrinth receptors, associated with
      a synchronous roll tilt of the body (at 0.15 Hz., +/- 12.5) leading to 2.5
      degrees out-of-phase neck rotation produced an adaptive increase in gain of the
      vestibulospinal reflex (VSR) elicited by roll tilt of the animal at 0.15 Hz, +/-
      10 degrees. This increase reached the maximum at the end of the third h of
      stimulation and persisted unmodified during the first h after stimulation.
      Microinjection into zone B of the cerebellar anterior vermis of the GABA-A
      agonist muscimol (0.25 microliter at 8 micrograms/microliters saline), producing
      only a slight or negligible depression of the VRS gain in non-adaptive
      conditions, prevented the occurrence of the adapted increase in gain of the VSR
      following a 3-h period of sustained head-body rotation. Moreover, intravermal
      injection of the GABA-A agonist muscimol or the GABA-B agonist baclofen (0.25
      microliter at 8 or 2 micrograms/microliters saline, respectively) suppressed the
      already adapted VSR gain. It is postulated that the adaptive increase in gain of
      the VSR following a sustained neck-vestibular stimulation depends on plastic
      changes which affect the Purkinje cells of the cerebellar anterior vermis.

PMID- 8749088
TI  - Role of muscarinic receptors in the cerebellar control of the vestibulospinal
      reflex gain: cellular mechanisms.
AB  - Most of the inhibitory Purkinje (P-) cells of the cerebellar anterior vermis fire
      out-of-phase with respect to the excitatory vestibulospinal neurons during roll
      tilt of the animal, thus exerting a positive influence on the gain of the
      vestibulospinal reflex (VSR). The responses of these P-cells depend on activation
      of glutamatergic excitatory mossy fibers-granule cells, but they are likely to be
      shaped by GABAergic inhibitory interneurons. The cerebellar cortex contains
      cholinergic fibers and both muscarinic and nicotinic receptors. In decerebrate
      cats intravermal injection of the muscarinic agonist bethanechol increased the
      VSR gain. The cellular mechanisms underlying these gain changes were studied in
      anesthetized Sprague-Dawley rats by microiontophoresis. Application of
      bethanechol (10-60 nA, 300 s) increased the response of vermal P-cells to pulses
      of glutamate (22/33 cells) or GABA (23/25 cells). These effects, which were
      blocked by the muscarinic antagonist scopolamine, lasted up to 15-40 min and
      occurred regardless of whether bethanecol altered the basal firing rate of the
      cells. We propose that the increase of P-cell responses to both excitatory and
      inhibitory neurotransmitters following activation of muscarinic receptors
      enhances the amplitude of modulation of these neurons to animal tilt, thus
      increasing the gain of the VSR.

PMID- 8749089
TI  - Release of glutamate from the vestibular nerve in the medial vestibular nucleus
      as a neurotransmitter: in vivo microdialysis study.
AB  - Histochemical and electrophysiological studies suggest that glutamate is the
      primary afferent neurotransmitter from the vestibular nerve to vestibular
      nucleus. To further examine this possibility, a microdialysis study using alpha
      chloralose-anesthetised cats was performed to elucidate whether glutamate is
      released from the vestibular nerve terminal in the medial vestibular nucleus
      (MVN). A microdialysis probe (CMA/10.2 mm) was inserted into the MVN and perfused
      with Ringer solution at 2 microliters/min. Samples were collected at 10-min
      intervals. Endogeneous glutamate was measured using the HPLC-ECD method. When
      electrical repetitive stimuli (200 microseconds duration, 0.5 mA, and 5 Hz) were
      given to the vestibular nerve for 10 min, an increase in the release of glutamate
      was observed in the MVN but not in the spinal trigeminal nucleus. These findings
      indicate that glutamate is the afferent neurotransmitter from the vestibular
      nerve to the MVN neurons.

PMID- 8749090
TI  - ABR findings in brainstem ischemia: occlusion of the left anterior inferior
      cerebellar artery.
AB  - ABR was measured ipsilaterally following permanent left anterior inferior
      cerebellar artery (AICA) occlusion to assess the discrepancy in recovery between
      blood flow and function in the rat brainstem. Three types of wave patterns were
      classified: in type 1, all components disappeared: in type 2, all components
      disappeared transiently, then re-appeared; and in type 3, only a significant
      increase in the latency difference between components I-IV was noted. In type 2,
      we suggest that all components re-appeared because cochlear blood flow was re
      established quickly by collateral circulation.

PMID- 8749091
TI  - Posterior canal-activated excitatory vestibuloocular relay neurons participate in
      the vestibulocortical pathways in cats.
AB  - We have previously reported that axon collaterals of posterior canal-activated
      excitatory vestibular (PC) neurons project to the contralateral oculomotor
      nucleus, and rostrally to the thalamus. To elucidate the vestibulothalamocortical
      pathways we investigated the synaptic connections of the PC neurons with the
      thalamic neurons by post-spike averaging of compound potentials triggered by
      spikes of the PC neuron in anesthetized cats. The averaged field potential evoked
      in the ventrobasal complex (VBC) revealed a spike followed by a negative wave.
      Latencies of the wave ranged from 0.8 to 1.5 ms. Next, we examined the location
      and axonal projection of 36 thalamic neurons which were activated by nose-up head
      rotation and by contralateral labyrinth stimulation. Most of them were located in
      the VBC and some in the medial geniculate body. Thirteen of the 36 neurons were
      antidromically activated from the anterior suprasylvian sulcus or postcruciate
      dimple of the cortex. These results suggest that the PC neurons participate, at
      least in part, in the vestibulocortical pathways contributing to spatial
      orientation.

PMID- 8749092
TI  - Post-natal development of tonic activity and membrane excitability in mouse
      medial vestibular nucleus neurones.
AB  - The development of tonic activity and membrane excitability of MVN neurones was
      examined using extracellular and intracellular recordings in slices prepared from
      mice at various stages in the first post-natal month. The tonic spontaneous
      discharge rates of MVN cells as post-natal day 5 (P5) were typically below 5
      imp/s, and gradually increased to reach adult values of 11-20 imp/s by P30. While
      most MVN cells at P5 were electrophysiologically immature, by P10-P15 they had
      developed overshooting sodium spikes and pacemaker conductances which generated a
      steady discharge of spontaneous action potentials. From the earliest stages when
      tonic activity was observed, immature forms of the adult Type A and Type B action
      potential shapes could be recognized in tonically active cells. There was a
      marked rostro-caudal gradient in the time course of the maturation of MVN
      neurones, with cells in the rostral part of the MVN firing at higher rates and
      having more mature action potential shapes than caudally located cells.

PMID- 8749093
TI  - Responses of locus coeruleus neurons to caloric stimulation in rats.
AB  - We examined the effects of caloric stimulation on the neuronal activity of the
      locus coeruleus (LC) and of the vestibular nucleus complex (VNC) in urethan
      anesthetized rats. The single unit activity of neurons in the LC and VNC was
      extracellularly recorded. A polyethylene tube for caloric stimulation was
      inserted into the middle ear cavity on the ipsilateral side. Through the tube,
      the middle ear was irrigated by hot (44 degrees C), cold (30 degrees C), and ice
      (4 degrees C) water. The majority of neurons in the VNC showed excitation by
      middle ear irrigation with hot water and inhibition by ice-water irrigation. The
      responses occurred during caloric stimulation and disappeared immediately after
      the cessation of the stimulation. The results suggest that the responses of VNC
      neurons to caloric stimulation directly reflect changes in primary vestibular
      afferent activity. On the other hand, the predominant effect of caloric
      stimulation with hot and cold water on LC neuronal activity was inhibitory. The
      suppression of LC neuronal activity occurred approximately 1 min after the
      cessation of the caloric stimulation and persisted for 3-5 min. The results
      suggest that LC neurons receive processed vestibular signals. Motion sickness and
      vestibular dysfunction induced by caloric stimulation cause emesis, which is
      known as vestibulo-autonomic response. The vestibulo-autonomic syndrome can be
      prevented by amphetamine, a noradrenaline releaser. Therefore, the inhibitory
      response of noradrenergic LC neurons to vestibular stimulation may be involved in
      the vestibulo-autonomic response.

PMID- 8749094
TI  - Clinical investigation of the vestibular cortex.
AB  - This study attempted to identify the vestibular cortex that is involved in the
      perception of vestibular vertigo in the human brain. We used single-photon
      emission computed tomography (SPECT) to measure regional cerebral blood flow
      (rCBF) in two cerebrovascular patients with nystagmus-sensation dissociation,
      which is known as brisk caloric nystagmus without simultaneous sensation of
      vertigo. Both patients had ischemic lesions involving mainly the parieto-temporal
      lobe in the nondominant hemisphere. It is suggested that the parieto-temporal
      lobe in the nondominant hemisphere contains the vestibular cortex which is a
      center for the perception of vertigo due to vestibular stimulation.

PMID- 8749095
TI  - Vestibular evoked responses: a new frontier in equilibriometry.
AB  - Modern neurootology has proved that many vertigo patients suffer from central
      dysequilibrium states. As vertigo patients are very frequent amongst our patient
      population we have to increase our diagnostic as well as therapeutical efforts.
      Since 1965, eliciting vestibular evoked cortical potentials has been possible. A
      method of evoked responses based upon computation of several stimulus responses
      has been used since then. Besides we are also using the frequency analysis of
      representative epochs of ongoing vestibular-ocular or retino-ocular reactions has
      been used since then. For diagnostic purposes we are combining various techniques
      like systematic history taking, ENG, ECG, CCG and BEAM. Brain electrical activity
      mapping (BEAM) is a newly developed tool, which we can also use for
      differentiating central from peripheral vestibular diseases. We are applying this
      technique for topographic correlates of vertigo related functional changes as
      well as for spatiotemporal analysis of cerebral evoked potentials due to
      vestibular stimulation. By means of a specific vestibular evoked potential
      technique, 6 typical cortical wave patterns can be elicited, which are displayed
      in the EEG curves as well as in colour maps of the whole scalp. The interactions
      between the various cortical structures are turning into an image similar to a
      weather map. BEAM, the fourth plan for projecting vertigo disorders, is now also
      bound into our concept for planning and monitoring a drug based therapy.

PMID- 8749096
TI  - Vestibular evoked responses in man: methodological aspects.
AB  - We have developed a stimulation method where the subject is sitting and the head
      is rotated with shock bursts elicited by a shaker with a repetition rate of 2 Hz.
      The head movement is monitored with an accelerometer mounted on the cheek by a
      head band. The maximum amplitude of the head movement is 3 degrees. The
      electrodes were places on vertex with a negative electrode on the mastoid. During
      stimulation, 90 dB white noise was applied to the ears to mask the noise
      generated by the stimulus. We recorded following responses: i) VER from
      ipsilateral ear, ii) VER from contralateral ear, iii) eye movement with EOG, and
      iv) movement of the head. Amplification and averaging of the signal were made
      with an evoked response recorder (Nihon Kohden, Neuropac four). From 200 to 2,000
      averaged responses were collected and stored for further analysis on a floppy
      disc. During second stage filtering the data were fed into a microcomputer where
      appropriate programs were used to eliminate the EMG and movement artifacts.

PMID- 8749097
TI  - Short latency vestibular evoked responses to linear acceleration stimuli in small
      mammals: masking effects and experimental applications.
AB  - Different potential were recorded from a site close to the 8th nerve in
      chinchillas in response to linear acceleration pulses. Acoustic masking allowed
      us to distinguish between an early response (within 1 ms after initiation of the
      acceleration) of probable vestibular origin and later responses of probable
      cochlear origin. The latter were abolished by intense acoustic masking and by
      surgical ablation of the cochlea. The early potential was slightly reduced by
      simultaneous acoustic masking with white noise above 65 dB SPL and was most
      sensitive to 1 kHz narrow band masking. Vestibular neurons seem to be stimulated
      by high frequency movements of their hair cell cilia, and vestibular compound
      action potentials can be recorded as soon as a sufficient number of neurons are
      brought to a synchronized response. These vestibular evoked potentials may
      provide a tool for experimental studies on vestibular function in laboratory
      animals.

PMID- 8749098
TI  - The clinical significance of vestibular evoked potentials (REP).

PMID- 8749099
TI  - Cortical responses of vestibular reactions measured by topographic brain mapping
      and vestibular evoked potentials.
AB  - With the brain electrical activity mapping, we started to create typical patterns
      of potentials distributions on the scalp during various neurootological
      experiments. We are applying this technique for spatiotemporal analysis of
      cerebral evoked potentials due to vestibular stimulation. We obtain the
      vestibular evoked potentials (VbEP) using for the stimulation, the rotatory
      chair. We control it, with an external computer, that by means of an interactive
      program builds different sort of stimuli varying each one of the stimulus
      components. The electrodes are distributed on the scalp in agreement with the
      international system 10/20. We recognize with security, 4 positive-negative waves
      in a period among 70 to 490 ms. We designate the waves N1, N2, P2, N3 and N4.
      Vestibular evoked potentials is a newly developed tool, which we also can utilize
      for differentiating central and peripheral vestibular diseases.

PMID- 8749100
TI  - Vestibular late evoked potentials (VbEP) processed by means of brain electrical
      activity mapping (BEAM).

PMID- 8749101
TI  - Neurootologic findings in patients with so called Meniere-like disease.
AB  - A group of 150 patients was clinically observed using a complete battery of
      neurootological methods. The patients were believed to suffer from Meniere's
      disease (MD). After taking anamnestic data [NODEC III] and performing
      calorimetry, cranio-corpo-graphy and audiology tests we could confirm a former
      established diagnosis of MD in a few cases only.

PMID- 8749102
TI  - Neuro-otological and neuropathological findings in two cases with Machado-Joseph
      disease.
AB  - We report chronological changes of neuro-otological findings and associated
      neuropathological findings in 2 patients. Concerning gaze limitation, upward gaze
      was primarily disturbed, followed by downward gaze and abduction. Adduction
      tended to be preserved although convergence was disturbed at the early stage.
      And, upward gaze limitation was followed by loss of oculocephalic responses
      (OCRs). Bell's phenomenon was preserved until the late stage of the disease.
      Caloric nystagmus was absent at the early stage. One patient showed dissociation
      between nystagmus and vestibulo-collic reflex in the caloric test at the early
      stage of the disease. Neuropathological examination revealed gliosis in the
      interstitial nucleus of Cajal and the MLF as well as neuronal loss and gliosis in
      the oculomotor nuclei. The vestibular nuclei also showed gliosis and atrophy of
      nerve cells.

PMID- 8749103
TI  - The auditory, vestibular, and oculomotor system in facioscapulohumeral dystrophy.
AB  - Auditory, vestibular and oculomotor function tests were performed in 14 FSHD
      patients (7 men, 7 women, aged 19-74 years) with autosomal dominant
      facioscapulohumeral dystrophy (FSHD) due to chromosome 4q35 associated DNA
      rearrangements. (Cochlear) sensorineural hearing loss (SNHL) in excess of that
      expected for their age was found in 6 patients: in 3 at the higher frequencies
      and in 3 also at the lower (speech) frequencies. Brain-stem auditory evoked
      potentials were generally normal. Oculomotor functions were normal. Four patients
      showed vestibular hyperreflexia, perhaps secondary to diminished head movements.
      Despite the apparent genetic homogeneity of the present patients, the above
      mentioned findings showed significant associations with certain families, the
      cases of new mutations, or a certain generation. Therefore, FSHD in our patients
      demonstrated clinical heterogeneity.

PMID- 8749104
TI  - Atypical "reversed" paroxysmal positioning nystagmus in benign paroxysmal
      positional vertigo.
AB  - An atypical paroxysmal positioning nystagmus (PPNy), "reversed" in its
      directional components, is a rare finding in patients suffering from benign
      paroxysmal positioning vertigo (BPPV). It poses problems of pathophysiogenetic
      interpretation, differential diagnosis with a CNS lesion and therapeutic
      strategy. Such a finding was observed in 7 patients (out of a total of 450 BPPV)
      and took on the typical PPNy pattern after repeated diagnostic manoeuvres. These
      aspects are incompatible with the "heavy cupula" mechanism (cupulolithiasis) and
      are better explained by the presence of "free endolymph aggregates"
      (canalolithiasis) within the posterior semicircular canal (p.s.c). Moreover,
      canalolithiasis would also permit a more convincing interpretation of all the
      clinical findings observed in typical p.s.c.-BPPV.

PMID- 8749105
TI  - Clinical application of ultrasonic blood rheography for vertigo.
AB  - The blood flow in the vertebral artery was measured in 507 patients with vertigo
      using ultrasonic blood rheography. In 150 of the 507 cases (32%), abnormal
      findings including laterality and decreased flow were detected. Twenty-one cases
      whose clinical course was observed showed a decrease in the differences in
      velocity between sides as vertigo improved. VBI (vertebro-basilar insufficiency)
      showed a worse prognosis in patients with laterality compared with those without
      and a positive correlation was demonstrated between side differences and
      fluctuating blood pressure or serum lipids. Some anti-vertiginous drugs improved
      the difference between sides by increasing the velocity.

PMID- 8749106
TI  - Magnetic resonance angiographic findings in vertiginous patients with slow
      vertebrobasilar blood flow.
AB  - To investigate arterial lesions underlying slow vertebrobasilar blood flow (SBF)
      which appears as a high intravascular signal on proton-density images, we
      examined 35 vertiginous patients, 15 with SBF and 20 without, using magnetic
      resonance angiography. Vertebrobasilar dolichoectasia, segmental stenosis with
      elongation and diffuse narrowing of the vertebrobasilar arteries (VBA) were found
      in 4, 4 and 2 patients with SBF, respectively. In one patient with SBF, the
      thrombi that induced SBF seemed to have embolized to distal arteries. These
      abnormalities were not detected in patients without SBF, although 2 patients
      demonstrated aneurysm in the VBA. Because SBF is frequently associated with
      atherosclerotic arterial lesions, patients with SBF should be treated to prevent
      more severe ischemic brain disease.

PMID- 8749107
TI  - Vestibular changes after guinea pig cytomegalovirus infection.
AB  - A guinea pig model of viral labyrinthitis was established by inoculating guinea
      pig cytomegalovirus into the inner ear and then determine its effect on
      vestibular function. Neither spontaneous nor positional nystagmus could be
      detected postoperatively. Nine out of 18 (50%) animals had caloric hyperfunction
      in the virus-inoculated ear at 1 to 3 weeks postoperatively. Five of these 9
      animals also had caloric hyperfunction in the control ear. A morphological study
      in animals with caloric hyperfunction showed no change in the peripheral
      vestibular apparatus by light microscopy. It is thus assumed that caloric
      hyperfunction in experimental viral labyrinthitis is transient and functional.

PMID- 8749108
TI  - Neuroactive substances in the human vestibular end organs.
AB  - In order to evaluate the involvement of neuroactive substances in the human
      vestibular periphery, the immunocytochemical distribution of substance P (SP),
      calcitonin gene-related peptide (CGRP), and choline acetyltransferase (ChAT) was
      examined. SP-like immunoreactivity (LI) was present around and beneath sensory
      hair cells, probably corresponding to their afferent nerve endings. SP-LI was
      found predominantly in subpopulations of the primary afferents distributed in the
      peripheral region of the end organs. ChAT-LI and CGRP-LI were found throughout as
      small puncta below the hair cell layer, probably corresponding to efferent
      endings. The present results indicate that these neuroactive substances,
      previously described in animals, are also distributed in the human vestibular
      periphery, and almost certainly contribute to human vestibular function.

PMID- 8749109
TI  - Gaba mediated long-term depression (LTD) in the rat medial vestibular nuclei.
AB  - As previously demonstrated, high frequency stimulation (HFS) of the primary
      vestibular afferents always induces a clear, long lasting depression of the
      polysynaptic (N2) component of the field potentials recorded in the dorsal
      portion of the medial vestibular nuclei (MVN). The induction of the HFS effect
      was mediated by the activation of glutamate NMDA receptors, since it was blocked
      by AP5. The mechanisms at the basis of such a depression were studied. Our
      results demonstrate that Gaba, acting on both GabaA and GabaB receptors, is
      involved in mediating this phenomenon. In fact, HFS applied during Bicuculline
      and Saclofen perfusion, was no longer able to induce an N2 depression, but
      provoked a slight potentiation. However, the N2 depression clearly emerged after
      drug wash-out. Furthermore, Bicuculline and Saclofen fully abolished the N2
      depression and highlighted the potentiation, when administered after HFS. The
      possibility that the N2 depression is the result of a homosynaptic LTD can be
      excluded on the basis of our results. On the contrary, our findings suggest that
      the depression is due to an enhancement of the Gaba inhibitory effect due to an
      HFS dependent increase in gabaergic interneuron activity, which resets vestibular
      neuron excitability at a lower level.

PMID- 8749110
TI  - The volume protective natriuretic peptide system in the inner ear. Comparison
      between vestibular and cochlear compartments.
AB  - It has been suggested that the family of natriuretic peptides (NP) has a
      protective role in volume overloading. Specific binding sites for atrial
      natriuretic peptide (ANP) and the kidney analog urodilatin (URO) were identified
      and quantified with computerized autoradiography and biochemical assay in the
      cryosection in the cochlear and vestibular (utricle/ampulla) tissue.
      Immunohistochemistry was used to identify and localize NP-like immunoreactive
      cells. Different levels of specific receptors between and within the inner ear
      compartments were detected. The presence of specific receptors for NP, as well as
      unequal distribution of NP-immunoreactivity between the compartments (in certain
      parts of the cochlea and the endolymphatic sac), may indicate a local autocrine
      and/or paracrine action of these peptide systems (presumably as a result of the
      integration of the different peptide effects), independent of their action via
      the more conventional systemic route, in addition to differences in response of
      the inner ear compartments to the load. The present results on specific binding
      of ANP and URO in the inner ear tissue may suggest physiological homology between
      the inner ear and the kidney. Moreover, a similar role of NP in these organs is
      suggested.

PMID- 8749111
TI  - In vivo regeneration of vestibular hair cells of guinea pig.
AB  - Recent studies have shown that inner ear sensory cells may regenerate in mammals
      as well as in birds. In this in vivo study we investigated the regeneration of
      vestibular hair cells in guinea pigs after gentamycin intoxication, and found
      that the vestibular sensory epithelia reproduced new hair cells 30 days after
      degeneration, due to 30 consecutive days of gentamycin treatment. From the
      regeneration pattern of sensory epithelia, the supporting cells were identified
      as the progenitors of hair cells.

PMID- 8749112
TI  - Effects of semicircular canal plugging on caloric nystagmus recorded in three
      dimensions.
AB  - In Rhesus monkeys, distinct eye movement response components in the planes of the
      semicircular canals (canal plane vectors, CPV) were identified by 3-dimensional
      recordings of caloric nystagmus elicited in different head positions relative to
      gravity. Surgical plugging of single semicircular canals (SCC) was used to
      identify the generators of these response components. The lateral CPV is a
      sinusoidal function of head position, compatible with a thermovective mechanisms
      in this canal. Surgical plugging of the lateral SCC leaves only a small head
      position independent, lateral CPV, probably due to direct temperature effects on
      lateral SCC afferents. The posterior and anterior CPVs are complex responses
      composed of various components of which the present plugging experiments
      identified two generators: i) effects of thermovection in the lateral SCC,
      demonstrated by modifications of posterior and anterior CPVs after occlusion of
      the lateral SCC; and ii) thermovection in the vertical SCCs, demonstrated by
      effects of plugging a single vertical SCC exclusively on the corresponding CPV.
      This is the first definite identification of the vertical SCCs as contributors to
      the generation of nystagmus induced by caloric irrigation of the outer ear canal.
      It may provide a basis for the development of a modified caloric test measuring
      more than only lateral canal function in human patients.

PMID- 8749113
TI  - In vitro electrogenic K secretion in the frog semicircular canal: absence of
      effect of streptomycin.
AB  - In vitro, the frog semicircular canal secretes an endolymph-like fluid, i.e. a K
      rich, positively polarized fluid. This electrogenic K secretion involved
      basolateral Na+, K(+)-ATPase and Na-K-Cl co-transporter and a luminal protein
      possessing sulfhydryl groups blocked by N-ethylmaleimide. Streptomycin, an
      ototoxic antibiotic, is known to block the non-specific mechano-dependent
      channels in the sensory cells of the ampulla of the semicircular canal. The aim
      of the present study was to investigate the possible effect of streptomycin on
      the K fluxes in the ampulla of the semicircular canal. The posterior frog
      semicircular canal was isolated and the lumen was filled with perilymph-like
      solution containing or not containing 0.5 mM streptomycin. The luminal K
      concentration and the transepithelial potential were measured and the
      unidirectional K fluxes calculated. The K influxes (into the lumen,
      pmoles/min/mm2) were 114 +/- 25.9 and 111 +/- 3.2 (mean +/- SE, n = 3) in the
      absence and presence of streptomycin, respectively. The transepithelial potential
      was not altered (4.0 +/- 1.08 mV versus 3.4 +/- 1.03 mV, n = 3). When ouabain
      (10(-3)M) was added to the basolateral solution together with luminal
      streptomycin, no further alteration occurred as compared with the effect of
      ouabain alone. These results suggest that in these conditions, the sensory organ
      does not have a major role in the endolymphatic K secretion in the ampulla of the
      frog semicircular canal.

PMID- 8749114
TI  - Effect of intratympanically administered gentamicin on hearing and tinnitus in
      Meniere's disease.
AB  - We have examined the effect of intratympanic gentamicin on hearing and tinnitus
      in 69 patients with intractable Meniere's disease. Tinnitus was scored from 1 to
      4 depending on its severity. The mean pure tone audiometry level before treatment
      was 57.5 dB and 1 year after treatment 63.5 dB Five subjects became deaf in the
      treated ear, and in 13 subjects hearing loss was > 10 dB and in 21 subjects 0 10
      dB. In 25 subjects significant improvement (> 10 dB) was gained, and in 5
      patients. Tinnitus was significantly reduced after treatment with gentamicin. A
      total of 66 patients had tinnitus before treatment and tinnitus relief was rated
      as good. Four percent of the subjects had no tinnitus, 30% had slight tinnitus.
      27% moderate tinnitus. 18% severe and 8% handicapping tinnitus.

PMID- 8749115
TI  - Evidence of somatic graviception from new and classical investigations.
AB  - Recent psychophysical experiments have provided evidence of an influence of
      graviceptors in the human trunk on the perception of body posture that equals or
      even surpasses the contribution of the otoliths. A reinterpretation of classical
      results on mammals, notably of the Utrecht school, leads to the conclusion that
      somatic graviceptors also partake in controlling the posture of eyes, neck and
      limbs.

PMID- 8749116
TI  - New diagnostic tests for the function of utricles, saccules and somatic
      graviceptors.
AB  - Clinical tests that allow us to discriminate between utricular, saccular and
      somatic effects on gravity perception and control are desirable but wanting. A
      new test battery is presented which combines four experimental paradigms based on
      the subjective horizontal body position (SHP), namely, a test on a tiltable board
      and on a sled centrifuge under varied leg position, with two paradigms based on
      the subjective visual vertical (SVV). It is shown by a combination of experiments
      and deductions, that, why, and how these tests can separate the effects of
      otoliths from those of somatic graviceptors, the effects of the utricles from
      those of the saccules, and the effects of the constituents of the somatic
      graviception from each other. The present study demonstrates the capabilities of
      the tests as well as their limitations.

PMID- 8749117
TI  - Visuo-vestibular interaction measurements: an alternative for rotation tests with
      better discriminatory power?
AB  - A vestibular function test is introduced for evaluating visuo-vestibular
      interaction (VVI), in which a visual target may move asynchronously with a pseudo
      randomly oscillating rotatory chair. The results show better discrimination of
      patients (Meniere's disease, benign paroxysmal positioning vertigo (BPPV),
      uncompensated peripheral vestibular lesions. whiplash) than do standard tests
      (torsion swing, velocity step, calorization, smooth pursuit, optokinetics,
      saccade analysis). For the phase shift, the better performance is shown to stem
      from improved reproducibility. Signal analysis is done fully automatically,
      thereby precluding experimenter's bias.

PMID- 8749118
TI  - Characteristics of human gait related variables in association with vestibular
      system disorders.
AB  - Gait analysis was performed in patients with vestibular system disorders, using
      foot switches and electromyography. They were divided into three groups: 11 cases
      with vestibular neuronitis (VN), 10 cases with large acoustic neuroma (LAN) who
      had central lesion evidenced by neurotological examinations, and 10 cases with
      olivopontocerebellar atrophy (OPCA). A total of 14 healthy adults served as
      controls. Results showed that time from heel strike to forefoot strike was the
      most sensitive variable to indicate gait abnormality but had no specificity. As
      for the variables of stance, swing, and time to reach the initial peak of the
      tibialis anterior's activity from forefoot off, occurrence rate of abnormality
      was high in the OPCA group, followed by the LAN and VN groups. Concerning the
      double support period which is related with body weight transfer from one leg to
      the other, the LAN and OPCA groups showed higher occurrence rate of abnormality
      than the VN group. These differences among the three groups could reflect
      different effects to the gait control systems caused by lesion.

PMID- 8749119
TI  - Predictive monitoring of high-frequency vestibulo-ocular reflex rehabilitation
      following gentamicin ototoxicity.
AB  - Nine patients exposed to gentamicin ototoxicity were tested with active head
      movements to determine their high-frequency (2-6 Hz) horizontal and vertical
      vestibulo-ocular reflex (VOR) responses. Results showed a common pattern
      documenting patients' reports of oscillopsia during walking: gains of 0.5 or
      less, and phases less than 180 degrees. A subset of these patients undergoing
      exercise rehabilitation therapy were tested repeatedly during follow-up visits to
      monitor changes in their VORs. VOR improvements toward reduced oscillopsia were
      correlated with patients' reported reduction of symptoms. Each patient's VOR
      changes over time were monitored with a quantitative least-squares method which
      predicted results of the next test, based on trends from three or more previous
      tests. The method was tested by comparing predicted results with actual test
      results, following the next test. Preliminary results show relatively accurate
      predictions up to 6 weeks in advance of actual tests, at least when trends of
      recent, previous tests were in a consistent direction. We conclude that
      predictive monitoring of changing VOR states can be useful for continuing, or
      modifying, the course of vestibular rehabilitation therapy, by providing
      quantitative prediction estimates of future results.

PMID- 8749120
TI  - Computer assisted data collection in vestibular disorders.
AB  - We have developed an interactive database for vertigo than can be used to assist
      in the diagnostic procedure and to store the data in a form of a database. The
      database offers the possibility to split and reunite the collected information in
      a desired way. The database contains detailed information about patient history,
      symptoms and findings in neurotological, audiological and imaging tests. The
      symptoms are classified into three sets of questions: vertigo (including postural
      instability), hearing loss and tinnitus, and provoking factors. Confounding
      disorders are screened. The neurotological tests involve saccades, smooth
      pursuit, posturography and caloric test. In addition, findings in specified
      antibody testing, clinical neurotological tests. MRI, brain stem audiometry and
      electrocochleography are included. The input information can be applied in an
      expert system ONE for vertigo work-up. The database is user-friendly. Besides
      diagnostic purposes the database is excellent for research purposes, and combined
      with the expert system it works as a tutorial guide for medical students.

PMID- 8749121
TI  - Reasoning in expert system ONE for vertigo work-up.
AB  - An otoneurological expert system (ONE) was developed to help collect data and
      diagnose the work-up of vertigo of both central and peripheral diseases causing
      vertigo. Patient history and otoneurological and other examination results are
      used in the reasoning process. The history is interactively collected and is
      complemented with clinical examination results. The case history data can be
      either mandatory or supportive. Mandatory questions are used to confirm a
      diagnosis, and conflicting answers are used to reject an unlikely disease.
      Supportive questions support or suppress a diagnosis, but their presence is not
      obligatory. The reasoning procedure of ONE scores every question independently
      for different diagnoses, depending on how well they agree with the symptom entity
      of a disease. Diagnostic criteria are set for each disease, in Meniere's disease,
      for example, the full triad is required. Graphic displays illustrate the linear
      and nonlinear correlation between the symptoms and diseases. For instance, both
      second-long Tumarkin-type attacks and attacks lasting hours give a high score
      while intermediately long attacks score much lower in Meniere's disease. To be
      able to take even rare diseases into consideration we try to diminish the
      possibility of a wrong decision rather than maximize the likelihood of reaching
      only one right decision.

PMID- 8749122
TI  - Clinical and electrophysiological findings in the Tullio phenomenon.
AB  - A 55 year old female with idiopathic Tullio phenomenon is presented. Binocular,
      scleral search eye coil recordings demonstrated a predominantly torsional left
      beating and vertical down-beating nystagmus in response to sound intensities over
      100 dB HL to the left ear, increasing in amplitude and slow phase velocity with
      sound intensity and removal of visual fixation. The vertical ocular movement was
      conjugate, i.e. without skew deviation. Neuro-imaging, all other neuro-otological
      features, including ipsilateral-contralateral stapedius muscle reflexes, and
      surgical exploration of the middle ear, were normal. Click-evoked vestibulo
      collic potentials were normal from the right ear but showed low threshold (70 dB)
      and increased amplitude from the left. There was no evidence that the Tullio
      phenomenon in this patient arises from stapes footplate hypermobility. The
      findings suggest that some cases of the Tullio phenomenon may be due to a
      hyperexcitability of the normal vestibular response to sound.

PMID- 8749123
TI  - Dose-related effects of alcohol on dynamic posturography and oculomotor measures.
AB  - Four healthy male volunteers < 30 years of age participated in a blinded study of
      placebo versus low (0.45 g/kg lean body weight = LBW), medium (0.80 g/kg LBW) and
      high (1.05 g/kg LBW) dose ethanol ingestion to investigate its effect upon gaze
      and posture control. Serial electronystagmography and computerized platform
      posturography were performed at different points along each subject's blood
      alcohol concentration (BAC) curve as measured by breath analysis. Smooth pursuit
      and positional testing revealed subtle abnormalities at sub-intoxicating BACs. In
      addition, instability on posturography was evident on the Sensory Organization
      Test with no statistically significant influence observed on muscle latency
      testing as determined by sway analysis. We conclude that even low ethanol BAC
      levels produce widespread gaze and posture control effects which can be easily
      documented.

PMID- 8749124
TI  - A quantitative analysis of head-shaking nystagmus of peripheral vestibular
      origin.
AB  - A quantitative analysis of horizontal head-shaking nystagmus (HSN) was made on 48
      patients with unilateral peripheral vestibular lesions in conjunction with
      stimulus intensity. Each patient underwent three head-shaking tests with 10, 30
      and 50 horizontal head-excursions at a frequency of approximately 2 Hz, and HSN
      was recorded on ENG with eyes open in total darkness. i) HSN appeared in a
      biphasic or monophasic pattern. ii) The maximal slow-phase eye velocity (MSV) of
      the 1st phase (PI) of biphasic HSN increased significantly in proportion to
      stimulus intensity, and was significantly greater than that of monophasic HSN.
      iii) The duration of HSN was greater in the 2nd phase (PII) of biphasic HSN than
      in PI and increased markedly in proportion to stimulus intensity. iv) As the
      stimulus intensity rose to a high level, the interval between PI and PII (2nd
      phase latency) shortened, and the PII tended to appear more quickly after head
      shaking. It was especially noteworthy that in response to an increase in stimulus
      intensity, both the MSV in PI and the duration of PII of biphasic HSN increased,
      but the duration of PI was reversely suppressed by the PII.

PMID- 8749125
TI  - Post caloric nystagmus: an analysis of culmination frequency and maximum slow
      phase velocity.
AB  - Neurons of the vestibular nuclei receive substantial afferent inputs from various
      parts of the cerebellum and brainstem. The efferent output of the vestibular
      nuclei thus reflects the interaction of these connections. This study
      investigates the influence of lesions of the posterior neuro-axis (PNA) on
      thermally induced nystagmus in 70 such patients. The caloric responses of all
      these patients were analyzed automatically with respect to culmination frequency
      (CF), but an automated analysis of SPVMax was possible in only 36 of these
      patients. Analysis of both sets of data showed that the coefficient of variation
      of SPVMax was significantly greater than that of CF. Vestibular decruitment,
      which correlates well with PNA lesions, was noted in 83% of cases when CF was
      used. In contrast, when SPVMax was used, vestibular decruitment was noted in only
      53% of patients. Considering the low coefficient of variation of CF and
      considering that vestibular decruitment is noted with greater reliability when
      this variable is used, it is recommended that caloric nystagmus should be
      analyzed with respect to frequency rather than SPVMax.

PMID- 8749126
TI  - Idiopathic perilymphatic fistulae: a temporal bone histopathological study.
      Clinical, surgical and histopathological correlations.
AB  - The temporal bone histopathological findings herein reported are the first to be
      from a patient who had, during life, the diagnosis of idiopathic perilymphatic
      fistulae. The patient received surgical treatment followed by rapid improvement
      of his vestibular symptoms. These specimens histopathologically demonstrate the
      patencies of the labyrinth capsule that were diagnosed (predicted) clinically
      during life, the qualities of the membranous labyrinth in both the operated and
      unoperated ears, and the elements of the surgical repair. Notably there is no
      evidence of endolymphatic hydrops. The diagnostic features which allowed this
      patient with fluctuating hearing loss, episodic vertigo, and tinnitus to be
      distinguished from a patient with Meniere's syndrome are discussed as are the
      implications regarding future and past studies of vestibular and cochlear
      disorders.

PMID- 8749127
TI  - The accuracy of the clinical diagnosis (predictability) of patencies of the
      labyrinth capsule (perilymphatic fistulas): a clinical histopathologic study with
      statistical evaluations.

PMID- 8749128
TI  - Nystagmus in benign paroxysmal positional vertigo: a three-component analysis.
AB  - Three-component analysis of nystagmus was carried out in 10 patients with benign
      paroxysmal positional vertigo (BPPV), focusing on the horizontal, vertical and
      torsional components, with the aid of a computerized eye movement analysis
      system. Using a pendular rotation stimulus we also measured three eye components
      of eye movement evoked from the vertical semicircular canals in 3 normal subject;
      two components (vertical and torsional) of nystagmus in patients with BPPV were
      compared with that of eye movements derived from the vertical semicircular
      canals. The time course of slow phase velocity of three components in BPPV
      patients was similar. In BPPV, the torsional component of eye movements was
      larger than that of the vertical component without obvious horizontal eye
      deviation. On the other hand, the vertical component from vertical semicircular
      canals was larger than that of the torsional component. From the view point of
      the vestibulo-ocular reflex, it is difficult to support the idea that the
      pathology of BPPV is localized only to the posterior semicircular canal.

PMID- 8749129
TI  - A preliminary report on the correlation of vestibular Meniere's disease with
      electrocochleography and glycerol test.
AB  - Objective evaluation of vestibular Meniere's disease has been difficult due to
      the lack of audiometric findings. Thus inevitably, the existence of vestibular
      Meniere's disease is constantly being challenged. In recent years,
      electrocochleography (ECochG) has proved to be a useful tool to verify the
      presence of endolymphatic hydrops electrophysiologically. To further clarify the
      nature of this disease, we collected 40 patients prospectively who met the
      following conditions as diagnostic criteria for clinical vestibular Meniere's
      disease: i) episodic vertigo, ii) aural fullness, and iii) normal hearing. We
      implemented the glycerol test and extratympanic ECochG in addition to routine
      survey in these cases. The diagnosis was confirmed if either test result was
      positive. A retrospective collection of 24 cases who underwent endolymphatic sac
      surgery was made to evaluate in retrospect the existence of endolymphatic hydrops
      indirectly proved by successful surgery. Results showed a positive SP/AP ratio in
      25 cases (62.5%) of which 7 had bilateral positive responses. The glycerol test
      was positive in 5 cases including 3 who also had positive ECochG responses. In
      the retrospective group, 4 cases exhibited an abnormally large SP/AP amplitude
      ratio at preoperative baseline conditions after general anesthesia. Twenty cases
      showed an SP/AP ratio within normal limits. Only 7 cases (29%) showed a decrease
      in the SP/AP ratio at different surgical steps. Short-term surgical results
      showed a 96% success rate of relief of vertiginous symptoms. Symptoms of fullness
      were completely controlled in 22 patients (92%). Hearing was preserved in 18
      patients (75%). We conclude that i) the above-listed clinical criteria combined
      with these objective tests may prove to be very useful in the diagnosis of
      vestibular Meniere's disease, and ii) a successful control of vertigo and aural
      fullness after endolymphatic sac surgery indirectly indicates that endolymphatic
      hydrops is involved in vestibular Meniere's disease, sharing as it does, a
      pathophysiology that is similar to that of classic Meniere's disease.

PMID- 8749130
TI  - Bilateral loss of vestibular function.
AB  - The clinical findings in 53 patients with bilateral vestibular failure (BVF) seen
      in a neurological hospital are reported. Bilateral acoustic neuromas were
      excluded. Seven patients (13%) had progressive cerebellar degeneration; these
      patients had no hearing complaints but showed gait ataxia, abnormal eye movements
      and cerebellar atrophy on neuro-imaging. Referral in these patients was primarily
      for eye movement assessment, and BVF was usually unsuspected. Neuropathies were
      present in 5 patients (9%), usually with normal central (brainstem-cerebellar)
      ocular motor function and variable patterns of hearing loss. The single largest
      group was idiopathic BVF (11 patients, 21%), patients presenting with vertiginous
      episodes, progressive unsteadiness or brief paroxysms of oscillopsia; auditory
      function, eye movements, neurological examination and imaging were usually
      normal. Nine patients (17%) suffered ototoxicity, mostly due to gentamicin;
      hearing was normal or mildly impaired. In 6 patients (11%) BVF was post
      meningitic, with concomitant auditory loss. Autoimmune disease was found in 5
      patients (9%); other organs were involved by the disease, and hearing was
      impaired but eye movements were spared. Miscellaneous neurological, otological or
      neoplastic diseases accounted for the remaining 10 patients. This study suggests
      that i) in patients with cerebellar degenerations, BVF may be underdiagnosed as
      the unsteadiness may be attributed only to the cerebellar disorder, ii) some
      patients with idiopathic BVF present with only minor visual or vestibular
      symptoms, and iii) detailed immunological screenings should be undertaken more
      often, in view of the significant proportion of patients with autoimmune and
      idiopathic BVF.

PMID- 8749131
TI  - Clinical survey of Meniere's disease: 574 cases.
AB  - Only 27% out of 574 patients suffering from Meniere's disease initially started
      with the typical Meniere's triad. A great advantage in order to diagnose
      Meniere's disease can be established with the telemetric-ENG. With this equipment
      it is possible to verify a nystagmus outside the clinic (at home, at work) at any
      time in patients suffering from vertigo attacks. Most of our patients showed an
      omnifrequent sensorineural hearing loss on the affected side. Many of our
      patients with Meniere's disease suffered from internal diseases (e.g. hypotonia,
      hyperlipidemia, diabetes mellitus), allergy or an affection of the paranasal
      sinuses, which may constitute co-factors triggering Meniere's disease.

PMID- 8749132
TI  - High-resolution MRI of the human cochlea.
AB  - The majority of magnetic resonance imaging (MRI) studies in neurotology concern
      the evaluation of retrocochlear pathologies or temporal bone lesions. Recently,
      quite a number of investigators have attempted to use imaging diagnosis to obtain
      a diagnosis and manifest the pathological findings of Meniere's disease. However,
      there is no evidence that endolymphatic hydrops in patients with Meniere's
      disease can be identified by imaging techniques. In this study we could depict
      Reissner's membrane clearer than before with the use of image processing. At the
      present time, we cannot apply the 2.11T MRI machine to patients under FDA
      regulation. We believe that MRI diagnoses of endolymphatic hydrops and small
      lesions of the internal structures of the inner ear will be possible in the near
      future.

PMID- 8749133
TI  - Nystagmus measured by ENG after stapes surgery.
AB  - Much attention has been paid to hearing results after stapes surgery, but the
      risks of vestibular disturbance has not been extensively studied. Postoperative
      spontaneous nystagmus was measured daily at bedside by portable ENG in order to
      evaluate the vestibular damage from stapes surgery. Thirteen patients underwent
      primary stapedotomy or stapedectomy from August 1, 1992 to June 30, 1993.
      Nystagmus toward the operated ear was observed in 3 cases, that toward the
      opposite ear in 2 cases, that changing from toward the operated ear to toward the
      opposite ear in 2 cases, that changing from toward the opposite ear to toward the
      operated ear in 2 cases and no nystagmus in 4 cases. There was no relationship
      between duration of nystagmus and that of dizziness. Nystagmus was thought to be
      due to the following: i) inner ear damage by operation, ii) postoperative
      perilymphatic fistula, iii) floating footplate, and iv) stimulation of hair cells
      by high potassium ion in the perilymph due to blood flow into the inner ear.

PMID- 8749134
TI  - The effect of unilateral posterior semicircular canal inactivation on the human
      vestibulo-ocular reflex.
AB  - The responses to rapid, passive, unpredictable, low amplitude (10-20 degrees),
      high acceleration (3,000-4,000 degrees/s2) head rotations were used to study the
      human vestibulo-ocular reflex (VOR) in pitch and yaw plane after unilateral
      posterior semicircular canal occlusion (uPCO) in 10 subjects. The results from
      these 10 uPCO subjects were compared with those from 18 normal subjects. The VOR
      gains at a head velocity of 200 degrees/s in the uPCO subjects were: pitch upward
      = 0.62 +/- 0.06, pitch downward = 0.87 +/- 0.11, yew ipsilesion = 0.78 +/- 0.06,
      yaw contralesion = 0.79 +/- 0.10 and in normal subjects were: pitch upward = 0.92
      +/- 0.06, pitch downward = 0.96 +/- 0.04, yaw right = 0.88 +/- 0.05, yaw left =
      0.91 +/- 0.12 (group means +/- twotailed 95% confidence intervals). The results
      showed that the pitch-vVOR gain was significantly (p < 0.05) decreased in
      response to upward head impulses whereas in response to downward, ipsilesion and
      contralesion head impulses were not significantly different (p > 0.05) from the
      normals. This study shows that there is 30% permanent residual deficit of the
      upward pitch-vVOR with an up-down asymmetry in pitch-vVOR gain following
      inactivation of a single posterior semicircular canal and that compensation of
      pitch-vVOR function is incomplete.

PMID- 8749135
TI  - A further critical assessment of the efficacy of endolymphatic sac surgery.
AB  - This paper further assesses the efficacy of two selected techniques of
      endolymphatic sac surgery (ELS) employing implants for the treatment of classic
      Meniere's disease and endolymphatic hydrops: the Arenberg inner ear valve implant
      and the newly developed Huang/Gibson inner ear shunt. Long-term (8-10 years)
      results for 57 patients given the Arenberg inner ear valve implant show that our
      demonstrated high success rate in achieving control of symptoms over the short
      term (1 year) is long-lasting and that although previously reported hearing gains
      have decreased in some cases, the overall long-term hearing results are better
      than for other surgical techniques. Preliminary results (less than 1 year) for 10
      patients treated with the Huang/Gibson inner ear shunt indicate that it is
      comparable in efficacy to the Arenberg implant, while 4 out of the 10 patients
      have shown remarkable hearing gain, as detailed in case reports. These results
      again illustrate and substantiate the authors' previous conclusion that, in cases
      where there is a definitive delineation of the endolymphatic sac and its lumen,
      and where the sac is anatomically suitable, ELS is undoubtedly an effective
      modality and should be the standard primary choice for intractable Meniere's
      disease.

PMID- 8749136
TI  - The risk of vestibular function loss after intracochlear implantation.
AB  - Sixty patients were selected for cochlear implantation and 50 of them received an
      intracochlear implant (Nucleus). Vestibular function was evaluated before and
      after surgery using a caloric test and a velocity step test. Sixteen patients had
      normal or residual vestibular function before surgery, 11 bilateral and 5
      unilateral; in 3 of the latter patients, the ear with vestibular areflexia was
      elected for implantation, which reduced the number of patients at risk for
      vestibular dysfunction to 13. Vestibular function was preserved in all of these
      patients except for 4; the risk of vestibular function loss can therefore be
      rated at about 31%.

PMID- 8749137
TI  - Middle ear imaging in neurotological work-up.
AB  - Middle ear imaging constitutes a homogeneous test battery for evaluation of
      neurotological disease. The imaging comprises infra-sound fistula test, ABR,
      tympanoscopy, ECoG, and trans-promontiorial cochlear blood flow measurement. We
      used a fistula test with infra-sound loading on posturography. In tympanoscopy we
      used 5 degrees and 25 degrees endoscopes with a diameter of 1.9 mm and length of
      125 mm. In blood flow measurement we used laser-Doppler system with a stainless
      steel tip placed on the basal turn against stira vascularis. The flux was
      analyzed with a computer with custom-made software. In ECoG, a silver ball
      electrode was placed on the round window. In 64 cases evaluated we were not able
      to verify a spontaneous PLF by tympanoscopy. Symptoms typical for spontaneous PLF
      with positive fistula test turned out to be caused by endolymphatic hydrops.
      Sudden deafness usually did not show reduced cochlear blood flow, but often an
      endolymphatic hydrops. Fistula test was positive in about 25% of cases with
      endolymphatic hydrops. Tympanoscopy caused very few complication. The procedure
      takes about one hour and is done ambulatorily.

PMID- 8749138
TI  - Postural control and vestibular function in patients selected for cochlear
      implantation.
AB  - Postural control and vestibular and eye motor function were evaluated in 7
      postlingually deaf patients before cochlear implantation as vibration toward the
      calf muscles or galvanic electrical stimulation of the vestibular nerves
      perturbed stance. The patients were compared with 21 control subjects. Vibration
      induced bodysway was increased in the patients compared to the normals. Galvanic
      stimulation induced a bodysway that was not significantly different from that of
      the control group suggesting that the patients selected for cochlear
      implantation, and with otherwise reduced postural control, are sensitive to
      electrical stimulation of the vestibular nerve. This finding may contribute with
      a complementary hypothesis to the causes of dizziness among cochlear implant
      patients.

PMID- 8749139
TI  - Using magnetic coil signals with EOG signals in computer analysis of vestibulo
      ocular reflex.
AB  - Since EOG signals are rather noisy, but magnetic coil signals almost noiseless,
      the latter type is a good reference to the former which is much easier to record.
      Concurrently recording magnetic coil and EOG signals we could verify some details
      as saccades which are often difficult to detect in noisy signals. It is important
      to recognise such phenomena in eye movement signals, because these affect the
      gain parameter computed between the vestibulo-ocular reflex signal and the head
      movement signal.

PMID- 8749140
TI  - Ocular movement during reading in patients with congenital nystagmus.
AB  - When a healthy person reads sentences arranged horizontally, the eye movement
      pattern is a series of regular saccades and rest periods. However, eye movements
      while patients with oculomotor disturbances are reading remain to be defined. In
      this study, 4 patients with congenital nystagmus (CN) were studied. Coordinated
      movements of eye and head are also studied by a new apparatus with terrestrial
      magnetism sensor. While subjects were reading, an eye movement pattern was
      superimposed by the CN waveform and showed few rest periods. Eye velocity of less
      than 4 degrees/s was noted in almost every cycle of the eye movements while the
      patients with CN were reading. When they were requested to read sentences and
      simultaneously rotate their head naturally, the head movements had the effect of
      cancelling the eye instability. This finding may be interpreted as a kind of "eye
      head coordination".

PMID- 8749141
TI  - Acquired pendular nystagmus: oculomotor and MRI findings.
AB  - The clinical, oculomotor and ophthalmological features of 27 patients with
      pendular nystagmus were studied in whom 22 also had MR imaging of the brainstem.
      The nystagmus was predominately horizontal in 4 patients, torsional in 5,
      vertical in 3 and mixed in trajectory in 8. Fifteen patients had conjugate
      nystagmus. Twelve patients had disconjugate nystagmus. Eight patients had INO. In
      16 patients visual acuity was 6/12 or worse. Acuity and the presence of INO were
      unrelated to the conjugacy of the nystagmus. The MRI cuts at the medullary,
      pontine and midbrain levels were analysed statistically to determine the areas
      where there was significant (< 0.05%) overlap between areas of abnormal signal in
      different patients. Significant target areas for lesions causing the nystagmus
      were: in the pons the medial vestibular nucleus, central tegmental and paramedian
      tracts; in the medulla the inferior olivary nucleus, reticular formation, dorsal
      accessory olivary nucleus, central tegmental tracts and olivo-cerebellar fibres;
      in the midbrain the red nucleus and central tegmental tracts. Horizontal pendular
      nystagmus was preferentially associated with pontine lesions and torsional
      nystagmus with medullary lesions. Patients with conjugate nystagmus had a
      tendency to have bilateral mirror image MRI lesions (p = 0.028). The prevalence
      of lesions in our patients raises a possibility that more than one neuronal
      mechanism must be affected to produce pendular nystagmus. The inferior olive may
      be responsible for the rhythm of ocular oscillation. The disruption of pathways
      proximal to the oculomotor nuclei may determine the instability in terms of
      individual eye movement.

PMID- 8749142
TI  - 3-D eye movement measurements on four Comex's divers using video CCD cameras,
      during high pressure diving.
AB  - Previous studies have shown the vulnerability of the vestibular system regarding
      barotraumatism (1) and deep diving may induce immediate neurological changes (2).
      These extreme conditions (high pressure, limited examination time, restricted
      space, hydrogen-oxygen mixture, communication difficulties etc.) require adapted
      technology and associated fast experimental procedure. We were able to solve
      these problems by developing a new system of 3-D ocular movements on line
      analysis by means of a video camera. This analyser uses image processing and
      forms recognition software which allows non-invasive video frequency calculation
      of eye movements including torsional component. As this system is immediately
      ready for use, we were able to realize the subsequent examinations in a maximum
      time of 8 min for each diver: oculomotor tests including saccadic, slow and
      optokinetic traditional automatic measurements; vestibular tests regarding
      spontaneous and positional nystagmus, and reactional nystagmus to the pendular
      test. For pendular induced nystagmus we used appropriate head positions to
      stimulate separately the lateral and the posterior semicircular canal, and we
      measured the gain by operating successively in visible light and complete
      darkness. Recordings were done during a simulated onshore dive to an ambient
      pressure corresponding to a depth of 350 m. The above examinations were completed
      on the first and last days by caloric tests with the same video system analyser.
      The results of the investigations demonstrated perfect tolerance of the
      oculomotor and vestibular systems of these 4 divers thus fulfilling the
      preventive conditions defined by Comex Co. We were able to overcome the
      limitations due to low cost PC computer operation and cameras (necessity of
      adaptation to pressure, focus difficulties and direct light exposure eye
      reflexions). We still have on line accurate measurements even on the torsional
      component of the eye movement. Due to this technological efficiency we also
      present some mathematical aspects of the software.

PMID- 8749143
TI  - Aging effects upon pursuit eye movements.
AB  - Quantitative assessment of aging effects upon pursuit eye movements was done in
      step-ramp stimulus conditions using 32 normal individuals. Eye movements were
      recorded with infrared reflection oculography. The target was a spot of 0.5
      degree red lazar light. The light spot was blanked for 5 ms while the mirror
      galvanometer moved to a new position. Eye and target position were sampled at 250
      Hz and analysed by a personal computer. In onward stimulation in which 2 degrees,
      4 degrees, 6 degrees and 8 degrees position steps were followed by fixed ramp
      speed (10 degrees/s), and also in backward stimulation in which 2 degrees, 4
      degrees, 6 degrees step positions were followed by 9 degrees, 17 degrees and 27
      degrees/s, eye acceleration increased depending upon increase of retinal slip
      velocity in the younger group below 49 years. Among the factors effecting aging
      effects, the cerebrum might be important because visual recognition and eye
      acceleration are performed in the parietal lobe.

PMID- 8749144
TI  - Pseudo random smooth pursuit test in patients with acoustic neuroma.
AB  - We examined the pseudo random smooth pursuit test in patients with
      cerebellopontine angle (CPA) tumors. Four different frequency combinations of
      sinusoids 0.15-0.35 Hz, 0.25-0.425 Hz, 0.3-0.7 Hz and 0.45-0.7 Hz were tested.
      Gain was calculated by comparing the smooth pursuit amplitude with stimulus after
      the supporting saccades had been removed. Phase was calculated by comparing
      maximum excursion of the eyes and stimulus. Gain was in the patients lower than
      in the controls in different frequency combinations, and the difference was
      statistically significant/highly significant in different frequency combinations.
      In the phase shift the differences were highly significant in the two higher
      frequency combinations and significant in the second frequency combination (0.25
      0.425 Hz), while in the first frequency combination (0.15-0.35 Hz) the difference
      was not significant. The gain method was a somewhat better analyzing method than
      the phase shift method.

PMID- 8749145
TI  - Ocular torsion position and the perception of visual orientation.
AB  - Previous studies have shown that in patients with unilateral vestibular
      deafferentation (UVD) there is a close relationship between the change in ocular
      torsional position consequent on the UVD, and the visually perceived orientation
      of short dim lines in an otherwise darkened room (1). However that result may
      have been confounded because the UVD may have affected both ocular torsion and
      sensory information about head position re gravity which must be used in making
      the visual perceptual judgement. Therefore we have sought a means of testing the
      relationship between ocular torsional position and the visual perception of
      orientation which was not confounded by the possible effect of changes in
      perceived head position.

PMID- 8749146
TI  - Yaw angular acceleration changes in human ocular torsional position.

PMID- 8749147
TI  - The effect of roll-tilt on ocular skew deviation.
AB  - Static roll-tilt of normal healthy subjects causes the ocular tilt reaction (OTR)
      one component of which is disconjugate vertical eye position (skew deviation). In
      this study the magnitude of skew was measured subjectively by the use of a
      computerized Hess test at three static roll-tilt angles (head erect, left ear
      down and right ear down) and two viewing distances (20 cm and 60 cm). The results
      showed that during static roll-tilt there was a small skew deviation, the
      magnitude of which was increased at close viewing distances.

PMID- 8749148
TI  - Influence of centrifugal force on angular velocity estimation.
AB  - In darkness, subjects were positioned face forward (or backward, resp.) on a
      rotating disk at a radial distance r of 0-1.6 m. They were then accelerated
      within 0.8 s to a constant rotation (omega = 0.35-0.87 rad/s), and successively
      indicated whenever they felt turned through 180 degrees. Fairly veridical at
      first, these indications lagged progressively as though subjective velocity
      declined exponentially to zero. Plots of ordinal number of indications over time
      of indication revealed idiosyncratic time constants (20-90 s) that were
      independent of disk velocity at r = 0, but increased with radial distance,
      namely, with r omega 2, hence depended on centrifugal force. When, after constant
      rotation of at least 2 min the subjects were stopped (within 1.2 s), and asked to
      indicate 180 degrees turns as above, the time constants of all subjects were
      independent of radius and disk velocity, as expected, if the added orthogonal
      force caused the prolonged time constants in the former paradigm.

PMID- 8749149
TI  - Effects of loratadine on postural control.
AB  - The effects of classical sedating antihistamines on cognitive and perceptual
      functions are well known. Loratadine is a new antihistamine without sedative
      effects. In this study, loratadine 10 and 40 mg daily, clemastine 2 mg twice
      daily and placebo were evaluated in 8 healthy subjects in terms of effects on
      equilibrium as measured with dynamic posturography. Dynamic posturography
      comprises a sensory organization part in which the support surface and visual
      surround are either stable or referenced to the patient's sway, with eyes open or
      closed. In a movement coordination part, the platform makes active movements.
      Analysis of variance showed no effects on equilibrium attributable to loratadine.
      Comparing substances pairwise, however, a significant difference between
      loratadine and clemastine was displayed in 2 out of 6 sensory test conditions. In
      conclusion, loratadine can be considered safe regarding balance functions.

PMID- 8749150
TI  - Postural control after propofol anaesthesia in minor surgery.
AB  - There is, not only from an economic perspective, a continuous search for surgical
      and anaesthetic procedures that allow out-patient surgery to be conducted.
      Reliable estimators of the patient's street fitness are of the utmost importance.
      Balancing capacity is one aspect that should be considered. Clinical methods like
      Romberg's are subjective and imprecise. Dynamic posturography comprises a movable
      support surface and visual surround that are either stable or referenced to the
      patient's sway, with eyes open or closed. In this study the recovery from
      propofol anaesthesia was studied in 8 patients who underwent surgery for minor
      microlaryngoscopic procedures. Dynamic posturography who performed before, and 2
      and 4 h after cessation of anaesthesia. All patients who were awake had normal
      balancing ability already at 2 h after anaesthesia. Further studies may supply
      additional information of other aspects of discharge after anaesthesia.

PMID- 8749151
TI  - Influence of cerebrospinal fluid tapping on dynamic equilibrium in suspected
      hydrocephalus.
AB  - Thirty-nine patients aged 21-82 years (mean 62 years) under investigation for
      suspected acquired hydrocephalus were investigated by dynamic posturography
      before and 6-8 h after a cerebrospinal fluid tap of 20-40 ml. Dynamic
      posturography comprises a sensory organization (SO) part in which the platform
      and visual surround are either stable or referenced to the patient's sway. The
      eyes are closed or open. In a movement coordination (MC) part the platform makes
      active movements, thus introducing external disturbances in the procedure. The
      patients improved their balancing ability in all tests on the sway referenced
      platform in SO, while MC remained unaffected. It is concluded that dynamic
      posturography is valuable for dysequilibrium assessment in clinical evaluation of
      suitable candidates for ventricular shunts in acquired hydrocephalus.

PMID- 8749152
TI  - Borreliosis as a cause of sudden deafness and vestibular neuritis in Sweden.
AB  - Twenty-one patients with unilateral sudden deafness and 16 patients with
      vestibular neuritis, all with typical clinical history and findings, were
      investigated for a possible borrelia-cause. Only one patient, a patient with
      vestibular neuritis, had evidence of active borreliosis in terms of high antibody
      titers in CSF, increased cell count and disturbed albumin ratio. To gain more
      knowledge about the etiological role of Borrelia burgdorferi in patients with
      hearing and vestibular symptoms, it is, despite this sparse finding, motivated to
      perform Borrelia testing in patients from tick-frequent areas. A reliable testing
      includes both serum and CSF analysis.

PMID- 8749153
TI  - Vestibular function in patients with a large vestibular aqueduct.
AB  - Four patients (7 ears) with a large vestibular aqueduct (VA) were examined for
      history of vertigo and vestibular function. Vertigo was observed in all the 4
      patients. The caloric responses were significantly poorer in ears with a large VA
      than in the controls. On a patient with a large VA who had several attacks of
      sudden hearing loss and vertigo following minor head trauma, long-time exposure
      to sunshine, common cold, and exercise, vestibular function tests were performed
      several times; the caloric responses were found to fluctuate and direction
      changing apogeotropic positional nystagmus was observed. These findings suggest
      that in patients with a large VA, not only hearing but also the vestibular
      function are generally impaired. We believe than direct transmission of
      intracranial pressure changes to the inner ear or subsequent inner ear fluid
      movement through the large endolymphatic sac and duct have an influence on the
      cochlea and vestibule.

PMID- 8749154
TI  - Quantitative evaluation of the Vestibular Autorotation Test (VAT) in normal
      subjects.
AB  - The Vestibular Autorotation Test (VAT) is a relatively easy method for testing
      the Vestibulo Ocular Reflex (VOR) at higher frequencies by asking the patient to
      actively shake his/her head from side to side (jaw) with increasing frequency. In
      this study we investigated reproducibility and clinical applicability of this
      method and quantified gain and phase of the VOR in normal subjects. We studied
      the VOR in 33 subjects over a frequency range from 2 to 6 Hz. Ten subjects were
      investigated with an angular rate sensor mounted on a headband. In this group the
      velocity gain tended to decrease at higher frequencies and phase lag increased
      slightly. In a second experiment (2 subjects) head velocity was detected
      simultaneously by an angular sensor fixed to a headband and an identical sensor
      attached to a bite board. It was shown that the gain of the VOR in the first
      group was underrated and phase shift overrated due to slippage of the headband
      fixed rate sensor. Therefore in a third experiment, 21 subjects were investigated
      with the rate sensor attached to a bite board only. In this group VOR gain was
      close to unity and phase was close to 0 degrees (180 degrees out of phase) from 2
      up to 6 Hz. In contrast to other studies, a considerable number of subjects were
      unable to reach shaking frequencies above 4 Hz. Our results agree with those of
      recently published reports and disagree with others, both using a headband. This
      is interpreted as being due to difficulties in sensing head velocity accurately.
      CONCLUSION: vestibular autorotation is an accurate and reproducible way of
      testing the high frequency range of the vestibulo-ocular reflex, provided that
      head velocity is measured by a bite board. Our present work is focused on
      determining the high frequency characteristics of the VOR in patients suffering
      from vertigo.

PMID- 8749155
TI  - Glutamate receptor gene family expressed in vestibular Scarpa's ganglion of rat.
AB  - The expression of glutamate receptor gene family in the vestibular Scarpa's
      ganglion (VG) of rat was determined using molecular biological techniques
      including reverse transcription (RT), polymerase chain reaction (PCR),
      amplification, DNA sequencing, and immunocytochemistry. Oligonucleotide primers
      were designed from the previously cloned sequences of the AMPA-selective
      glutamate receptors (GluR1-4), KA-selective glutamate receptors (GluR5-7, KA1&2),
      NMDA-selective glutamate receptors (NMDAR1&2), and metabotropic glutamate
      receptors (mGluR1-4). The cDNAs synthesized from the VG mRNAs were amplified with
      the specific primers for the subunits of each glutamate receptor gene family.
      Analysis of the nucleotide sequences of the amplified cDNAs identified the
      expression of GluR1-4, GluR5, and NMDAR1 in the VG. Sequence analysis identified
      the expression of all the four subunits of GluR1-4 in two alternative spliced
      versions named "flip" and "flop" in the VG. In an immunocytochemical study, a
      large number of VG neurons showed only GluR2/3-like immunoreactivity (IR) while
      GluR1- or GluR4-IR could not be determined in the VG. The present study suggested
      that the subunits of GluR1-4, GluR5, and NMDAR1 may be assembled into the hetero
      oligomeric glutamate receptor complex in the VG and that the VG neuron-specific
      stoichiometry of the receptor complex may be functionally significant for the
      afferent signal transduction in the rat peripheral vestibular system.

PMID- 8749156
TI  - Vision during motion in patients with absent vestibular function.
AB  - We have measured a spatial visual response and visual velocity discrimination in
      4 patients with long standing vestibular loss and 6 controls. The spatial
      response was measured during; i) body and visual display stationary conditions,
      ii) whole-body oscillation (1 Hz +/- 50 degrees/s) and iii) visual stimulus
      oscillation (1 Hz +/- 50 degrees/s). Velocity discrimination was assessed during
      conditions i) and ii). The visual tests applied were selected on the basis that
      the spatial response is known to reflect peripheral processes of the retina,
      whereas velocity processing is more central in origin. Patients had normal
      spatial responses under static conditions and they suffered a degradation in
      their spatial responses during whole-body oscillation, whereas, normals'
      responses remained unaltered. During oscillation of the visual display both
      patients and normals suffered a degradation in their spatial responses, and for
      patients the change was very similar to that observed during whole-body
      oscillation. The changes in the spatial responses were dependent on the gain of
      the eye movements which compensated for the whole-body or visual display
      oscillation. In 3 patients and all controls whole-body oscillation did not alter
      the discrimination of velocity of a vertically moving horizontally orientated
      grating compared with when the subjects were stationary. One patient suffered a
      severe reduction in the ability to discriminate velocity under whole-body
      oscillation, which suggests that central suppression of motion perception reduces
      oscillopsia.

PMID- 8749157
TI  - Thresholds for perception of lateral motion in normal subjects and patients with
      bilateral loss of vestibular function.
AB  - Thresholds for detection of direction of whole-body lateral linear acceleration
      were determined for normal (N) and labyrinthine defective (LD) subjects.
      Thresholds for 67% correct detection of direction of acceleration steps for 5 LDs
      (mean 5.65 cm/s2, peak gradient = 25 cm/s3) were not significantly different from
      8 Ns (mean 4.84 cm/s2, peak gradient = 22 cm/s3). High inter-subject variability
      was found both among the 7 Ns and 3 LDs for detection of parabolic accelerations
      with some individuals being unable to detect their motion direction. Mean Ns
      thresholds were 15.2 cm/s2 for a ramp with gradient of acceleration = 2.8 cm/s3,
      26.4 cm/s2 for a ramp with gradient = 7.9 cm/s3 and 20.2 cm/s2 for a parabola
      with second derivative = 1.52 cm/s4. Thresholds for LDs were respectively 19.1
      cm/s2, 32 cm/s2 and 26.7 cm/s2. The lower thresholds for acceleration steps
      demonstrate the important effect of acceleration gradient on motion detection.
      For all stimuli, thresholds for some LDs could be in the range of Ns showing that
      somatosensory signals can play a significant role in detecting lateral
      acceleration.

PMID- 8749158
TI  - EMG-responses to sudden onset free fall.
AB  - Recordings of axial and limb muscles in reaction to a free fall induced startle
      were performed in subjects while they were lying on a tilting couch with their
      eyes closed. Young normals (n = 24, aged 31.1 +/- 6.6 years) showed an activation
      sequence consisting of sternomastoid (N.XI: 57 ms), abdominal muscles (T10: 65
      ms), quadriceps (L3: 75 ms) and deltoid (C5: 78 ms) and tibialis anterior (L4: 80
      ms). The sequence of activation is not compatible with the current hypothesis of
      the startle being produced by a single volley spreading rostrally and caudally
      from the lower brainstem. Instead it is suggested that the startle is a patterned
      response organized by a putative reticular generator capable of spatio-temporal
      sequencing. Two avestibular patients had responses at mildly delayed latencies,
      showing that these can be elicited by non-vestibular inputs. Similar testing of
      11 subjects aged 70-80 years showed a latency delay of ca. 26% in the EMG
      response but a similar activation sequence. The amount of delay in the elderly
      can only partially be attributed to age-dependent motor conduction slowing and
      suggests a prolongation of central processing time. In patients with advanced
      stages of akinetic-rigid syndromes abnormalities were seen in cases with an
      involvement of the brainstem reticular formation.

PMID- 8749159
TI  - Apogeotrophic type of direction-changing positional nystagmus related to slow
      vertebrobasilar blood flow.
AB  - We examined the incidence of slow blood flow (SBF) in the vertebrobasilar system
      by magnetic resonance imaging (MRI) in 35 patients showing direction-changing
      positional nystagmus (DCPN). The subjects consisted of 20 patients with
      apogeotrophic type (group A) and 15 with geotrophic type (group B) of DCPN. Fifty
      seven age-matched subjects without vestibular symptoms were examined as a control
      group (group C). SBF was detected in 11 (55%), 3 (20%) and 6 (11%) patients in
      groups A, B and C, respectively. Lacunae of the brainstem were found in 7 (35%)
      patients in group A and 1 (7%) in group B. The higher incidence of SBF in group A
      suggested a possible relationship between SBF and apogeotrophic type of DCPN.
      Apogeotrophic type of DCPN associated with SBF was considered to be caused by
      ischemia in the posterior circulation, though it was unclear whether the
      vestibular labyrinth or the hindbrain was mainly involved.

PMID- 8749160
TI  - Modeling human vestibular responses during eccentric rotation and off vertical
      axis rotation.
AB  - A mathematical model has been developed to help explain human multi-sensory
      interactions. The most important constituent of the model is the hypothesis that
      the nervous system incorporates knowledge of sensory dynamics into an "internal
      model" of these dynamics. This internal model allows the nervous system to
      integrate the sensory information from many different sensors into a coherent
      estimate of self-motion. The essence of the model is unchanged from a previously
      published model of monkey eye movement responses; only a few variables have been
      adjusted to yield the prediction of human responses. During eccentric rotation,
      the model predicts that the axis of eye rotation shifts slightly toward alignment
      with gravito-inertial force. The model also predicts that the time course of the
      perception of tilt following the acceleration phase of eccentric rotation is much
      slower than that during deceleration. During off vertical axis rotation (OVAR)
      the model predicts a small horizontal bias along with small horizontal, vertical,
      and torsional oscillations. Following OVAR stimulation, when stopped right- or
      left-side down, a small vertical component is predicted that decays with the
      horizontal post-rotatory response. All of the predictions are consistent with
      measurements of human responses.

PMID- 8749161
TI  - Calcium dependent intercellular interaction of the neural crest derivate
      melanocytes and the epithelial cells of the vestibular organ.
AB  - As recently established in several species, the presence of neural crest derivate
      melanocytes is essential for the development of the epithelial cells regulating
      the ion and the potential gradients in the inner ear. The interaction between the
      melanocytes and the epithelial cells appears to be activated when intracellular
      Ca2+ increases. This may be due to a disturbance of the Ca2+ homeostasis under
      hydropic conditions or to the effect of the Ca-ionophore (A 23187) or hormone
      (alpha-MSH). Lowering of extracellular Ca2+ blocked the effect of the drug at the
      basal level. The interaction of the melanocytes with the epithelial or
      endothelial cells differs significantly. It is indicated that melanocytes may be
      under hormonal control and that their activation and intercellular interaction
      are related to the increase of intracellular Ca2+ and may be controlled by
      extracellular Ca2+. Furthermore, we propose that melanocytes provide a regulatory
      network for the maintenance of the inner ear homeostasis.

PMID- 8749162
TI  - Vertical and torsional VOR in posterior canal occlusion.
AB  - The vertical and torsional vestibulo-ocular reflexes (VOR) were investigated in 3
      patients with surgical occlusion of the posterior semicircular canal and 1
      patient with singular neurectomy, for treatment of refractory paroxysmal
      positional vertigo. Stimuli comprised sinusoidal oscillation in the coronal
      ("roll") and sagittal ("pitch") plane as well as in two oblique planes
      intermediate between pitch in order to stimulate left anterior + right posterior
      (LARP) and right anterior + left posterior (RALP) canal pairs separately. One
      case with left side BPPV was investigated pre and post-operatively. Depression of
      the vertical and torsional VOR gain was seen 1 week postoperatively when the
      occluded canal was placed in the optimal plane for stimulation at 1 week
      postoperatively and subsequently gradually recovered. Recordings in other planes
      suggested that the contralateral posterior canal was also hypofunctioning, a
      finding which may explain some residual gait unsteadiness in this case. The other
      3 cases who were investigated postoperatively all showed a decrease in downward
      VOR gain in the "on' direction of the operated canal. The data indicate the
      specificity of the test procedure and underline the prognostic value of
      comprehensive pre-operative vestibular assessment.

PMID- 8749163
TI  - Observation of positional nystagmus with infrared CCD camera.
AB  - Using infrared CCD camera and electronystagmography we analyzed positional
      nystagmus in 33 patients with peripheral positional vertigo. Patients were
      classified into three types; (a) lateral type: nystagmus occurs in lateral
      position, (b) sagittal type: nystagmus occurs in head-hanging position (so-called
      benign paroxysmal positional vertigo, BPPV), and (c) mixed type. Nystagmus in the
      lateral type was horizontal and that in the sagittal type was rotatory. In all
      types, the vertigo and nystagmus began with a few seconds' latency after head
      tilt and briefly increased to a maximum, and then gradually decreased. The
      duration of horizontal nystagmus in the lateral and mixed type was significantly
      longer than that of rotatory nystagmus in the sagittal type mixed type. The mean
      value of the former was 90.6 s and that of the latter 18.1 s. We suggest that the
      velocity storage mechanism of the horizontal vestibulo-ocular reflex (VOR) is
      considerably different from that in the vertical VOR.

PMID- 8749164
TI  - Three-dimensional (3-D) eye movement analysis in patients with positioning
      nystagmus.
AB  - Benign paroxysmal positioning vertigo (BPPV), and nystagmus (BPPN) is the
      commonest type of rotational vertigo. Typical BPPN is generally believed to arise
      from one posterior semicircular canal. If this is true, the syndrome would offer
      the unique possibility to study vestibular responses when just one single
      semicircular canal is excited. In this study we used search coils to measure 3-D
      eye positions in 3 patients with BPPN. We present a complete 3-D description of
      the eye movements induced in BPPN. We found that in our patients the eyes rotate
      rather precisely in the plane of one posterior semicircular canal, suggesting
      that BPPN in our cases is indeed solely produced by the posterior semicircular
      canal.

PMID- 8749165
TI  - Imaginary gaze effects on eye movements induced by linear acceleration:
      involvement of vestibular induced smooth pursuit eye movement.
AB  - We investigated smooth eye movements elicited i) by linear acceleration in a
      space-fixed imaginary gaze condition (smooth component of eye movement induced by
      linear motion: LSEM) and ii) during acoustic pursuit of a moving sound source
      (smooth component of eye movement induced by acoustic pursuit of a sound source:
      SSPEM). The two conditions were examined using the same test subjects. LSEM and
      SSPEM performance was found to be positively correlated across the subject
      population. From the comparison of LSEM and SSPEM we propose the following
      hypothesis: LSEM consists not only of a pure translational vestibular-ocular
      reflex (tVOR) component but also of a component based on the perception of
      otolithic information. Accordingly, this second component is instrumental in the
      pursuit of an imaginary visual target during linear self-motion.

PMID- 8749166
TI  - Demonstration of intermediate filament proteins in the guinea pig vestibular
      labyrinth by a new, high-resolution cryotechnique.
AB  - In order to establish the more precise localization of IFPs in the vestibular
      labyrinth we have developed an immunohistochemical method using semithin
      cryosections from guinea pig inner ear. The vestibular end organs were fixed by
      intralabyrinthine perfusion with formaldehyde and glutaraldehyde. Microdissection
      was performed, followed by decalcification in EDTA. After specimen embedding in
      gelatin, semithin cryosections (1 micron) were prepared. Prior to the
      immunohistochemical staining, a new antigen-unmasking treatment was performed.
      Monoclonal antibodies for cytokeratins (Cks), vimentin, neurofilament protein
      (NF), and glial fibrillary acidic protein (GFAP) were used and visualized with an
      indirect ABC method. In the guinea pig vestibular labyrinth, Cks8, 18 and 19 were
      present. Vimentin and NF were stained positively, GFAP negatively. These results
      are in accordance with our previous results in the human vestibular labyrinth
      except for Ck7. The high-resolution cryotechnique in combination with a new
      antigen-unmasking method may yield more, and more detailed information about the
      localization of IFPs in the vestibular region.

PMID- 8749167
TI  - The role of L-threo DOPS in the control of Na-K ATPase activity of the marginal
      cells in the stria vascularis of reserpinized guinea pigs.
AB  - It is believed that the function of the stria vascularis in the cochlea is to
      produce endolymph. The mechanisms that maintain or control the function of the
      stria vascularis, however, remain unclear. In a previous study, we investigated
      the ultracytochemical effects of one-shot reserpine administration on the Na-K
      ATPase activity of the stria vascularis in guinea pigs. Na-K ATPase activity was
      shown to be completely inhibited 3-20 days after reserpinization, whereas in the
      present study at 20 days after reserpinization and following L-threo DOPS
      treatment, Na-K ATPase activity was detectable. As reserpine is an adrenergic
      neuron blocker, and L-threo DOPS is the precursor of noradrenaline, it seems that
      noradrenaline converted from L-threo DOPS was able to restore the Na-K ATPase
      activity in the reserpinized animals. These results suggest that catecholamines
      may play an essential role in the maintenance or control of the Na-K ATPase
      activity, and that the stria vascularis may be one of the target organs of
      catecholamines.

PMID- 8749168
TI  - The influence of unilateral vertebral artery occlusion on bilateral inner ear
      blood flow in rats.
AB  - We investigated the influence of unilateral vertebral artery (VA) occlusion on
      bilateral inner ear blood flow in rats using laser Doppler flowmetry for the
      measurement of bilateral cochlear blood flow (CBF) and photochemically initiated
      thrombosis for VA occlusion. BP and CBF showed little change by unilateral VA
      occlusion alone. However, subsequent hypotension induced by venesection not only
      reduced CBF but also caused imbalance between bilateral CBF reduction rates. CBF
      changed independently of BP, indicating the existence of a local CBF regulatory
      system.

PMID- 8749169
TI  - The perception of head rotation in Parkinson's disease.
AB  - The accuracy in detecting angular displacements of the head and the neck was
      investigated in 14 patients with idiopathic Parkinson's disease (PD) and 16 age
      matched normal controls by the technique of vestibular and cervical "remembered"
      saccades. It was found that although the remembered saccades in PD patients were
      multiple-step and showed low initial saccadic gain, the final eye position of the
      eyes matched the rotational stimulus as accurately as in normals. This indicates
      that perception of head/neck rotation is normal in PD which is inconsistent with
      views that vestibulo/proprioceptive dysfunction contributes to the postural
      disorder in PD. The presence of multiple-step remembered vestibular and cervical
      saccades agrees with reported abnormalities in visual remembered saccades in PD
      and indicates that the difficulty in generating saccadic movements based on
      memorized sensory information is not confined to visual-memory.

PMID- 8749170
TI  - Oculomotor abnormalities in Dyssynergia cerebellaris myoclonica.
AB  - In 1921 Ramsay-Hunt first described the syndrome of dyssynergia cerebellaris
      myoclonica (DCM), characterized by the clinical triad of action myoclonus,
      progressive ataxia and epilepsy with cognitive impairment, subsequently also
      referred to as the "Ramsay-Hunt syndrome". The cause of the symptoms of this rare
      degenerative syndrome (incidence: 500,000) is the impairment of a regulatory
      mechanism between nucleus dentatus, nucleus ruber and the bulbar olive. We
      present two sisters, aged 29 and 30 years, who were investigated for oculomotor
      abnormalities. The patients were diagnosed as having DCM according to clinical
      symptomatology, which was confirmed by neurophysiological and radiological
      findings. In both cases saccadic velocity was markedly reduced, whereas saccadic
      latency showed a significant increase. In addition, smooth pursuit eye-movements
      were abnormal and presented reduced gain. These findings suggest that pontine
      areas and the vestibulocerebellum also seem to be affected in DCM.

PMID- 8749171
TI  - Vestibular modulation of the septo-hippocampal cholinergic system of rats.
AB  - Effects of vestibular stimulation on the in vivo release of hypothalamic
      histamine and hippocampal acetylcholine (ACh) were investigated in urethan
      anesthetized rats, using a brain microdialysis method. Changes in glutamate
      concentration in the medial vestibular nucleus (MVN) were also monitored by a
      microbiosensor technique using a glutamate oxidase-embodied platinum electrode.
      Caloric stimulation with hot water increased the glutamate release in the MVN,
      while that with ice water decreased it. It is evidenced that glutamate is a
      neurotransmitter between afferent vestibular nerve and the MVN. Electrical
      stimulation of the round window evoked the release of hypothalamic histamine and
      hippocampal ACh and these effects were inhibited by the blockade of second-order
      vestibular neurons by the pre-injection of 6,7-dinitroquinoxaline-2,3-dione
      (DNQX), an antagonist of non-N-methyl-D-aspartate (non-NMDA) glutamate receptors,
      into the ipsilateral vestibular nucleus. Caloric stimulation with both hot and
      ice water increased the release of hypothalamic histamine and hippocampal ACh. It
      is suggested that both the histaminergic and cholinergic systems were activated
      by the imbalance of intervestibular activities. Depletion of neuronal histamine
      by alpha-fluorometylhistidine (FMH), an irreversible inhibitor of histamine
      synthesis, did not suppress the vestibular evoked release of hippocampal ACh. In
      contrast, caloric stimulation did not evoke hypothalamic histamine release in
      rats treated with ethylcholine aziridiniun ion (AF64A), a putative cholinotoxin.
      All these findings suggest that the vestibular information activated the
      histaminergic neurons via the activation of the cholinergic neurons and this
      neuronal circuit was involved in the vestibulo-autonomic response.

PMID- 8749172
TI  - Increased platelet aggregability in patients with vertigo, sudden deafness and
      facial palsy.
AB  - Many patients suffering from episodic vertigo have no cochlear symptoms. These
      patients have so far been diagnosed as having Meniere's disease of the vestibular
      type. However, the underlying mechanisms are still to be established. In the
      present study, we investigated platelet aggregability in patients with dizziness,
      Meniere's disease, sudden deafness and facial palsy, to examine whether
      abnormalities in platelet aggregation is one of the causes of episodic vertigo.
      In 36 patients with dizziness, in 13 with Meniere's disease, in 7 sudden
      deafness, and in 7 facial palsy, platelet aggregability to adenosine diphosphate
      (ADP) was assessed by optometric technique. It was found that platelet
      aggregability was increased in the patients with dizziness as well as with
      Meniere's disease, sudden deafness and facial palsy and only the two former
      patient groups showed a tendency of hyperlipidemia. The administration of
      antiplatelet and lipidemia drugs resulted in no recurrence of vertigo during at
      least 3 months' follow-up. Hence, the results of our study suggest that a
      possible initializing factor of vertigo without cochlear symptoms might be
      disturbed microcirculation due to platelet hyperaggregability.

PMID- 8749173
TI  - Changes in Fos and Jun expression in the rat brainstem in the process of
      vestibular compensation.
AB  - By means of immunohistochemical technique, we examined the changes in Fos and Jun
      expression after unilateral labyrinthectomy (UL) in the rat brainstem. We
      observed Fos-like immunoreactivity (-LIR) in the ipsilateral medial vestibular
      nucleus (ipsi-MVe), the contralateral prepositus hypoglossal nucleus (contra-PrH)
      and the contralateral inferior olive beta subnucleus (contra-IOb) 1 h after UL.
      Then, Fos expression in the contra-PrH and the contra-IOb disappeared 3 days
      after surgery. However, we still found the residual expression in the ipsi-MVe,
      which disappeared within 7 days. On the other hand, no Jun-LIR was detected in
      the vestibular or vestibular-related nuclei before or after the operation. Fos
      expression in the MVe, PrH and IOb was induced immediately after UL. Then, the
      Fos expression disappeared in accordance with the development of the vestibular
      compensation. These findings suggest that the transient Fos expression in the
      vestibular and vestibular related nuclei is a trigger of vestibular compensation.

PMID- 8749174
TI  - Recovery from bilateral vestibular failure: implications for visual and cervico
      ocular function.
AB  - We report a patient who sustained severe bilateral labyrinthine lesions during
      Streptococcus suis meningitis but considerably recovered vestibular function over
      a 7 month period. This unique case allowed us to examine the cervico-ocular
      reflex (COR) and visual function at various levels of activity of his vestibular
      system. The slow phase COR, elicited by trunk oscillation (0.2 Hz) with the head
      earth-stationary, was negligible immediately after the acute vestibular loss but
      rose to a gain of 0.51 one month after. Seven months later, when vestibular
      function was improved, COR gain dropped to a gain of 0.15. Measurements of
      spatial visual function during whole body oscillation in the acute stage and
      after 6 months showed marked improvement which correlated entirely with VOR
      measurements in the dark and during optic fixation. This patient also showed the
      unique feature that, in the acute stage, eye movement gain and visual function
      were poorer during whole body motion than during identical visual target motion.
      These findings suggest that: i) the COR may be inhibited by the presence of
      vestibular signals, ii) spatial vision measurements provide accurate assessment
      of the patient's visual blur during head motion, and iii) the severe oscillopsia
      experienced by patients in the acute stage of vestibular loss may not only be due
      to the absence of the VOR; additional degradation in eye movements during head
      motion, perhaps arising from acutely distorted labyrinthine signals, may also
      play a part.

PMID- 8749175
TI  - Perceptual studies in patients with vestibular neurectomy.
AB  - Twelve patients undergoing unilateral vestibular neurectomy for the treatment of
      refractory vertigo were investigated. Vestibular motion perception was assessed
      using a self-rotational task and "vestibular remembered saccades". Cervical
      perception was also measured with remembered saccades. The tests were performed
      pre- and post-operatively to examine changes in vestibular and cervical
      perception following an acute vestibular lesion, and to monitor the progress of
      vestibular compensation. These perception tests were carried out in conjunction
      with a conventional evaluation of the vestibular ocular reflex (VOR), using
      electro-oculography. The patients' subjective symptoms at each stage of testing
      were also quantified with questionnaires. Generally, in the vestibular tests, for
      stimulation to the operated side, responses became strongly hypometric directly
      after the neurectomy, with a partial recovery during convalescence. In the
      cervical test, responses were bilaterally reduced immediately after operation.
      Results from both of the vestibular perception tests were significantly
      correlated with the VOR assessment of vestibular function. Scores for the
      patients' subjective symptoms of "vertigo" were only significantly correlated
      with the vestibular perception tests, and not with the conventional measures of
      vestibular function. Perceptual measurements afford useful complementary
      information in the assessment of vestibular patients.

PMID- 8749176
TI  - Influence of a cold front upon the onset of Meniere's disease in Toyama, Japan.
AB  - In order to clarify the influence of a cold front (CF) upon the onset of
      Meniere's disease (MD), major CFs were defined by meteorological observations,
      and the influence of CFs on MD was evaluated by using the time n method. From our
      preliminary study it was seen that the onset of MD had its highest incidence
      exactly on days where a CF passed by. Out of the patients with MD, sudden
      deafness (SD) and Bell's palsy (BP) who visited our neurotological clinic of the
      Toyama Medical and Pharmaceutical University from 1987 to 1992, 67 MD patients,
      70 SD patients and 70 BP patients could clearly define the date of the onset of
      their disease, and were therefore selected for this epidemiological study. Thirty
      six our of the 67 MD patients had the first attack on the day when a CF passed by
      or on the next day. The results obtained from these studies were as follows. i)
      The onset of MD was influenced by the passing of a CF, and this influence was
      more specific in MD than in SD or BP. ii) In the 36 CF influence MD patients, the
      majority were over the forty years, and their hearing level was worse than that
      of the other 31 MD patients during the observation periods.

PMID- 8749177
TI  - Epidemiological study of severe cases of Meniere's disease in Japan.
AB  - In order to clarify the characteristics of severe cases of Meniere's disease
      (MD), we analyzed various epidemiological factors such as sex ratio, past
      history, complication, cause of onset of vertiginous attacks, etc., in a series
      of 958 patients with definite MD. Data were obtained from the three Japan-wide
      surveys of MD conducted by the Meniere's Disease Research Committee of Japan
      (1975-76) and the Vestibular Disorders Research Committee of Japan (1982-84 &
      1990). Following the ideas proposed by the members of the Vestibular Disorder
      Research Committee of Japan, we divided severe cases into three categories
      according to the following criteria i) bilateral MD cases (BMD), ii) unilateral
      MD cases with prolonged disabled vertigo (UPDV), iii) unilateral MD cases with
      profound hearing loss (UPHL). About 40% of the subjects were classified as severe
      cases (UPDV: 23%; BMD: 9%; UPHL: 6%). The ratio of otitis media in past history
      was statistically different between severe cases and non-severe patients (p <
      0.05), suggesting that otitis media in the past may contribute to the severity of
      Meniere's disease.

PMID- 8749178
TI  - Modification of parameters in vertical optokinetic nystagmus after repeated
      vertical optokinetic stimulation in patients with vestibular lesions.
AB  - Eye movements were recorded in patients with unilateral and bilateral vestibular
      lesions after upward and downward optokinetic (OK) stimulation before and
      following 6 weeks' repeated exposure to OK stimulation. In control subjects there
      was no asymmetry between upward and downward slow-phase velocity (SPV). Before
      training, less subjects showed that upward and downward SPV was significantly
      lower than that of controls. There was no asymmetry between upward and downward
      SPV. After training, in unilateral cases, the values of both upward and downward
      SPV recovered to the control range. In bilateral cases, the downward SPV values
      returned to the control range, whereas the values of upward SPV exceeded the
      control range. The frequencies of both upward and downward OKN in controls were
      about 3.0 Hz. In unilateral and bilateral cases, before and after training, the
      OKN frequencies approximated 3.0 Hz, showing no significant differences. The
      recovery of the SPV in unilateral and bilateral cases after training suggests
      that OK stimulation acts to stabilize the body and consequently to provoke
      pronounced OKN, due to eye-head-body co-ordination. The asymmetry of SPV after
      training in bilateral cases might be a result of the lack of otolith function.

PMID- 8749179
TI  - Videonystagmoscopy: its use in the clinical vestibular laboratory.
AB  - Vestibular function of a population including labyrinthine-defective patients and
      a control group of age-matched normal healthy volunteers was evaluated using
      videonystagmoscopy. This device is made of one or two CCD infra-red cameras
      mounted on diving glasses and allows observation of ocular movements on a video
      monitor and/or recording on a videotape. Eye movements are observed after
      rotations in a Barany chair and during passive head tilts. With this simple and
      non-invasive test, a screening of vestibular function at bedside or during ENT
      clinical investigations can be performed. A further study with
      videonystagmography to quantify these results being prepared.

PMID- 8749180
TI  - New representations of otolithic primary afferent spatial tuning--a re-processing
      of the Fernandez & Goldberg (1976) data.
AB  - In 1976 Fernandez & Goldberg published detailed results of the polarization
      vectors for squirrel monkey primary otolithic afferents (1). Each vector
      represented the direction in three-dimensional space of the linear acceleration
      which caused maximum facilitation of the otolith afferent. The published plots
      were separate views of the projections of the polarization vectors of all the
      individual neurons in the superior (mainly utricular) and inferior (mainly
      saccular) divisions of the vestibular nerve. There were distinctly different
      clusters of vectors for each division. We have used new computer graphic
      procedures to re-process these data and show the data three-dimensionally in
      relation to the major planes of the head.

PMID- 8749181
TI  - Infrared/video ENG recording of positional nystagmus in subjects with peripheral
      vestibular disease.
AB  - We performed simultaneous infrared/video and electronystagmorgraphy (ENG)
      recordings of eye movements in 417 patients with disequilibrium. Of that number,
      54 patients with the following two criteria participated in this study: verified
      diagnosis of peripheral vestibular disease and the presence of positional
      nystagmus recorded by ENG and an infrared/ video recording system. Although
      horizontal nystagmus was the most common, torsional, vertical and oblique
      nystagmus were also demonstrated in these patients. The most striking finding was
      the high incidence of oblique nystagmus closely related to a significant right
      left difference of the caloric response in benign positional vertigo.

PMID- 8749182
TI  - Posturography: head stabilisation compared with platform recording. Application
      in vestibular disorders.
AB  - Posturography with simultaneous recording of the head movements (H-recording) and
      of the pressure of the feet on the platform (P-recording) has been applied in
      patients with peripheral vestibular disorders. For the whole testing (four tests
      with visual and proprioceptive interaction) 40% showed an identical degree of
      abnormality for the measurements of surface in P- and H-recording. In a large
      majority of the patients, showing a difference between H- and P-recording, this
      difference indicated a lower degree for the H-recording. Concerning the four
      tests separately, the differences for eyes closed tests were more frequently
      positive (larger surface for head movements) than for eyes open tests. Also on
      foam rubber there was more difference than on stable platform. Especially the
      test with eyes closed on foam rubber showed more differences. These data show
      that in a minority of patients the comparison of H-recording and P-recording
      affords complementary information showing in these cases some independence of
      head stabilisation and foot-stabilisation. Head-recording can be used as a
      posturographic technique but one has to keep in mind the possible differences
      with platform-recording.

PMID- 8749183
TI  - Caloric tests on platform: "paradoxical responsiveness".
AB  - This paper deals with the abnormal responsiveness of the paradoxical stabilizing
      type (SR) occurring after caloric tests (CALT) performed on a passive force
      platform. The normal response after CALT (cold/warm, monaurally performed)
      consists of transient ataxia and body sway towards the side of the nystagmic slow
      phase induced by a similar CALT. Quantitatively the vestibular responsiveness to
      CALT is defined as the quotient of lengths QL calculated with measures of
      recordings after CALT (cold and warm responses averaged) versus recordings at
      rest. A normal vestibular responsiveness is defined as 1.5 < QL < 2.5; a
      vestibular lesion corresponds to QL around 1.0 (0.8-1.2); the paradoxical
      stabilizing responsiveness SR-CALT corresponds to QL < 0.65 and represents a
      particular type of lesional response. We observed SR-CALT in 23 patients from a
      total of 135 patients with similar lesions (SR excepted) after CALT at the
      vestibulo-ocular and vestibulo-spinal levels. SR-CALT appeared unilaterally in 11
      patients, bilaterally in 12 patients. About half of the patients were followed up
      (1-4 years) and later exhibited total lesions but no more SR-type responses. All
      the patients had chronic- or bilateral vestibular lesions, with acute worsening
      of vertigo complaints and a spell-like lesional evolutivity, due to Meniere's
      disease or evolutive lesions of diverse origin. Additionally other tests,
      particularly those involving the neck-vestibular interactions, could induce SR
      type responses in these patients. The significance of SR-CALT is discussed and we
      hypothesize that SR possibly represents a particular kind of vestibular
      "decompensation" at the vestibulospinal level in cases of chronic but recent
      evolutive vestibular lesion.

PMID- 8749184
TI  - Impaired postural control in patients with cervico-brachial pain.
AB  - Dizziness and subjective balance disturbances are common complaints in cervical
      pain syndromes. We assessed balance function with posturography using vibration
      induced and galvanically-induced body sway in consecutive patients (n = 116) with
      cervico-brachial pain syndrome of more than 3 months' duration. A total of 83% of
      the patients showed signs of cervical root compression on MRT scans. The
      incidence of complaints of vertigo was 50%. The patients manifested significantly
      poorer postural control than sex- and age-matched controls (n = 20). Disorders of
      the neck should be considered when assessing patients complaining of dizziness,
      vertigo and balance disturbances.

PMID- 8749185
TI  - Vestibular stimulation perturbs human stance also at higher frequencies.
AB  - The effect of primary vestibular disturbance on postural control was investigated
      in 11 normal subjects exposed to perturbation by bi-polar binaural galvanic
      stimulation of the vestibular nerve. The stimulus consisted of 30 s of sinusoidal
      galvanic stimulation at frequencies of 0.2, 0.3, 0.5, 1.0, 1.5, 2.0, 3.0 and 4.0
      Hz, with a current of +/- 1 mA, the subject standing with open or closed eyes and
      the response evoked being recorded with a force platform. As compared with
      resting values, i.e. no stimuli, variance of lateral body sway was significantly
      greater at all frequencies tested in the closed eyes condition and at frequencies
      of 0.2, 0.5, 1.0, 3.0 and 4.0 Hz in the open eyes condition; using a high pass
      filter with a cut-off frequency of 0.1 Hz, variance of lateral body sway was
      significantly greater at frequencies 0.2, 0.3, 0.5, 1.0 and 2.0 Hz in the closed
      eyes condition and at frequencies 0.5 and 2.0 Hz in the open eyes condition.
      These findings suggest that in the lateral plane vestibular input affects and
      probably contributes to human postural control over a wider frequency range than
      suggested by findings in previous studies. Moreover, the visual contribution
      appears to enable the subject to suppress vestibular input causing lateral body
      sway only in the lower frequency range (here at 0.2 and 0.3 Hz). This evidence of
      vestibular contribution to postural control in the lateral plane is consistent
      with the response characteristics of the vestibulo-ocular reflex.

PMID- 8749186
TI  - Randomized perturbed posturography in abstinent chronic alcoholics.
AB  - Equilibrium is maintained by visual, proprioceptive and vestibular afferent
      influx, central coordination and motor efferents. Eleven male abstinent chronic
      alcoholic volunteers aged 44-65 years (mean 57 years) were investigated by
      randomized perturbed posturography. They had all been long time heavy drinkers.
      Ocular smooth pursuit and visual suppression of the vestibulo-ocular reflex
      showed abnormalities in a previous study, but they had no signs or symptoms of
      polyneuropathy. The current study demonstrated larger (but generally not
      significantly so) sway areas, and in all tests on the randomly moving support
      surface the sway velocities were significantly larger than in the controls. It is
      concluded that randomized perturbed posturography is valuable in dysequilibrium
      assessment in chronic alcoholics.

PMID- 8749187
TI  - Vestibular plasticity following orbital spaceflight: recovery from postflight
      postural instability.
AB  - Results of previous studies suggested that the vestibular mediated postural
      instability observed in astronauts upon return to earth from orbital spaceflight
      may be exacerbated by an increased weighting of visual inputs for spatial
      orientation and control of movement. This study was performed to better
      understand the roles of visual and somatosensory contributions to recovery of
      normal sensori-motor postural control in returning astronauts. Preflight and
      postflight, 23 astronaut volunteers were presented randomly with three trials of
      six sensory organization test (SOT) conditions in the EquiTest system test
      battery. Sagittal plane center-of-gravity (COG) excursions computed from ground
      reaction forces were significantly higher on landing day than preflight for those
      test conditions presenting sway-referenced visual and/or somatosensory
      orientation cues. The ratio of summed peak-to-peak COG sway amplitudes on the two
      sway-referenced vision tests (SOTs 3 + 6) compared to the two eyes closed tests
      (SOTs 2 + 5) was increased on landing day, indicating an increased reliance on
      visual orientation cues for postural control. The ratio of peak-to-peak COG
      excursions on sway-referenced surfaces (SOTs 4, 5 & 6) to an earth fixed support
      surfaces (SOTs 1, 2 & 3) increased even more after landing suggesting primary
      reliance on somatosensory orientation cues for recovery of postflight postural
      stability. Readaptation to sway-referenced support surfaces took longer than
      readaptation to sway-referenced vision. The increased reliance on visual and
      somatosensory inputs disappeared in all astronauts 4-8 days following return to
      earth.

PMID- 8749188
TI  - C. S. Hallpike and C. O. Nylen--some recollections of the founders of The Barany
      Society.

PMID- 8749189
TI  - Various methods for testing nasal responses in vivo: a critical review.
AB  - Mucosal responses in the airway can ideally be studied in the nose. It is a
      readily accessible organ and can be provoked repeatedly. Likewise, mucosal
      responses to certain provocations can be easily monitored. Different methods for
      the provocation and measurement of nasal responses have been used in recent
      years. Each technique has its own advantage and restrictions. In order to make a
      correct interpretation of the results achieved, however, it is important that the
      investigator is familiar and comfortable with the methods used. For clinical
      purposes, techniques for qualitative measurements may be appropriate, but for
      experimental research, quantitative measurements with high reproducibility are
      essential. The present paper critically discusses current techniques for
      provocation and assessment of nasal responses, which may improve both the
      techniques used and the understanding of nasal physiology.

PMID- 8749190
TI  - Otolith function tests in patients with unilateral vestibular lesions.
AB  - This study was designed to assess the utility of otolith-ocular reflex testing in
      patients with complete unilateral peripheral vestibular deficits. Ten subjects
      were given a clinical vestibular test battery (ENG & vertical rotation) and
      research oriented tests of otolith function including dynamic posturography with
      head tilt and earth-horizontal axis rotation with otolith-visual interactions.
      Clinical tests confirmed the presence of a vestibular deficit and the side of the
      lesion. The results suggested the following: posturography during head tilt is
      not a reliable means of detecting unilateral peripheral vestibular dysfunction,
      while earth-horizontal axis rotation is a reliable means of assessing asymmetric
      otolith function. The Bias response during earth-horizontal axis rotation was
      significantly less during rotation ipsilateral to the lesioned ear compared to
      contralateral rotation while the Mod response was normal. The optokinetic test
      results in these subjects were normal while otolith-visual interactions were
      symmetrically reduced in these patients.

PMID- 8749191
TI  - Heart beat modulation of spontaneous otoacoustic emissions in guinea pig.
AB  - It has been reported that background variation in the frequency of spontaneous
      otoacoustic emission (SOAEs) may arise from the cardiovascular system and that
      the side-bands in the spectra of SOAEs may be modulated by heartbeat. For better
      understanding of the mechanical influence of the cardiac cycle on cochlear
      functions under physiological and pathophysiological conditions, this study
      investigated heartbeat-induced modulation of SOAEs in guinea pig. Possible
      mechanisms of these phenomena are also discussed. The external ear canal acoustic
      signal, round window electric signal, and the ECG were recorded for off-line
      analysis from five pigmented guinea pigs with SOAEs. Time and frequency domain
      averages with synchronization of the heartbeat indicate that both the external
      ear canal acoustic and round window electric signal contain some component
      contributed by ECG and phonocardiography. High resolution FFT spectra suggest
      that SOAEs were modulated by heartbeat and respiration. Theoretically the change
      in the SOAEs could be from frequency modulation or a combination of frequency and
      amplitude modulations. Results of a heartbeat-synchronized average of a wave
      analyzer output at SOAE frequency indicates that amplitude modulation of SOAE
      does occur. Data obtained in the current experiment support the hypothesis that
      the heartbeat-related modulation of SOAE in guinea pig is a combination of
      frequency and amplitude modulation. The proposed mechanism is that pulsatile
      cochlear blood flow may cause oscillations in cochlear pressure and affect
      cochlear performance, resulting in heartbeat modulation of SOAEs.

PMID- 8749192
TI  - Short term effects of induced middle ear pressure changes on the
      electrocochleogram in Meniere's disease.
AB  - Electrocochleographic recordings were made in 17 patients with Menier's disease
      before and immediately after exposure to pressure applications in their middle
      ear. The variables of the response to clicks such as the SP/AP ratio and the
      width of the complex as well as the amplitudes of the SP in response to long tone
      bursts were evaluated. Improvement of electrocochleographic recordings,
      characterized by normalization of the waveforms and reduction of the SP, was
      found to be significant. The results indicate a mechanoelectric change in the
      hydroptic cochlea registered directly after exposure to middle ear pressure
      changes.

PMID- 8749193
TI  - Natural killer cell response in the inner ear.
AB  - Heterologous tumor cells (human chronic myelogenous leukemia K-562 cells) were
      injected into the perilymph and skin in guinea pigs in order to study the
      induction of NK cell activity in the inner ear. An in vitro transmission electron
      microscopic and immunohistochemical study showed that K-562 cells were attacked
      by guinea pig large granular lymphocytes. K-562 cells injected through the round
      window membrane were found to be targeted by NK cells emerging from surrounding
      venules after 7 to 9 days. During this time morhological changes occurred in the
      organ of Corti and stria vacularis. These findings suggest that the inner ear
      response to foreign cells induces activation and invasion of NK cells which occur
      relatively late compared with those in other organs such as skin.

PMID- 8749194
TI  - The influence of unilateral vertebral artery occlusion on brainstem and inner ear
      blood flow in rat.
AB  - We investigated the influence of unilateral VA occlusion on blood regulation in
      the brainstem and the inner ear, using laser-Doppler flowmetry in rat. Chemical
      control was evaluated by blood flow response to CO2 inhalation, and
      autoregulation by that to induced hypotension. The results were as follows: i)
      Unilateral VA occlusion impairs chemical control and autoregulation of brainstem
      blood flow and affects autoregulation in the inner ear. ii) Unilateral VA
      occlusion damages the potential for blood flow regulation more strongly in the
      brainstem than in the inner ear. These results suggest that occlusive disease
      within the vertebro-basilar system leads to the impairment of blood flow
      regulation in both the brainstem and the inner ear-more strongly in the brainstem
      possibly contributing to symptoms such as vertigo and hearing disturbance, at
      least in certain groups of patients when hemodynamic factors such as systemic
      hypotension are added.

PMID- 8749195
TI  - Influence of changed blood pH on anionic sites in the labyrinth.
AB  - Using polyethyleneimine as a cationic probe, changes in the anionic sites of the
      labyrinthine basal laminae occurred during acidosis and alkalosis. Hartley-strain
      guinea pigs (200-300 g) with normal Preyer's reflex were injected i.v. with 0.5%
      polyethyleneimine (PEI, mol. wt 1800) solution adjusted to pH 7.3 with HCI via an
      axillary vein. The animals were divided into three groups: control, acidosis, and
      alkalosis. Acidosis was produced by inducing hypoxia, and alkalosis by injecting
      7% NaHCO3. In controls, anionic sites were demonstrated on the basal laminae in
      the labyrinth. During both acidosis and alkalosis, a decreased number of anionic
      sites were observed on the basal laminae of the capillary walls in both stria
      vascularis and subepithelial layer of the vestibular sensory epithelium. However,
      an increase in anionic sites was observed on the basal lamina in Reissner's
      membrane during both acidosis and alkalosis.

PMID- 8749196
TI  - Effect of endolymphatic hydrops on capsaicin-evoked increase in cochlear blood
      flow.
AB  - Capsaicin, which causes release of neuropeptides including substance P, has been
      shown to cause dose-related increases in cochlear blood flow (CBF). Since CBF
      regulation is altered in animal models with endolymphatic hydrops, this study was
      designed to examine the effect of hydrops on capsaicin-induced CBF changes. CBF
      responses to 0.01 and 0.001% capsaicin applied to the round window membrane were
      measured in normal and 12-week hydropic guinea pigs using laser Doppler
      flowmetry. With 0.01% capsaicin, CBF increased by only 13 +/- 7.8% in the
      hydropic ear, compared with 34% +/- 13% in the normal animal (p = 0.027). With
      0.001% capsaicin, CBF increased by only 7.5 +/- 4.2% in the hydropic ear,
      compared with 28 +/- 16% in the normal ear (p < 0.001). These findings
      demonstrate a reduced responsiveness to capsaicin with endolymphatic hydrops and
      suggest that hydrops causes an alteration in the peptidergic sensory fibers of
      the inner ear or in the vascular smooth muscle or both. The results are
      consistent with previous reports of reduced vascular responsiveness in hydropic
      guinea pigs and provide further evidence for abnormal CBF regulation in hydrops.

PMID- 8749197
TI  - Mechanically induced calcium increases in isolated vestibular hair cells of the
      guinea pig.
AB  - Intracellular Ca2+([Ca2+]i) is elevated by depolarization or mechanical
      stimulation in some hair cell systems. It is not clear whether both these stimuli
      promote Ca2+ entry in mammalian vestibular hair cells. We monitored [Ca2+]i with
      the indicator fluo-3 in isolated type I vestibular hair cells of the guinea pig
      maintained in Hanks' balanced salt solution (HBSS). Mechanical stimulation by
      bolus application of HBSS led to an immediate rise of [Ca2+]i. The effect
      depended upon the presence of extracellular Ca2+([Ca2+]o) and no increase
      occurred in calcium-free HBSS supplemented with calcium-chelators. When the cells
      were depolarized by bolus application of KCl (final concentration, 100 mM KCl in
      modified HBSS), the increase in [Ca2+]i was similar to that elicited by HBSS. In
      the absence of [Ca2+]o, the application of KCI/HBSS led to a slow sustained
      increase in the fluorescence of the cells suggesting release of calcium from
      intracellular stores. Finally, treatment of cells with BAPTA prior to mechanical
      stimulation prevented the rise in [Ca2+]i indicating the need for intact
      stereociliary tip-links. The results are consistent with the hypothesis that
      mechanical stimulation elevates [Ca2+]i in isolated vestibular hair cells via
      calcium influx through mechanotransduction channels.

PMID- 8749198
TI  - The suspensory ligament of the endolymphatic duct in the rat. An ultrastructural
      study.
AB  - Following optimized fixation and specimen handling, the endolymphatic duct was
      investigated by transmission and scanning electron microscopy. Tubular
      microfibrils, 10-12 nm thick and of indefinite length, occupied the subepithelial
      compartment abundantly and seemed to insert into the basal lamina of the
      epithelial cells of the duct and to merge with the bony wall of vestibular
      aqueduct thus forming a suspensory ligament of the endolymphatic duct. This
      ligament is suggested to protect the endolymphtaic duct from collapsing and to
      play a role in the mechanical protection of the vestibular apparatus from sudden
      increases in intracranial pressure. The capillaries and the aqueductal vein were
      located in intimate relationship to the epithelial cells. Both types of vessels
      were provided with fenestrations of the endothelial cells, supporting the
      proposal that the endolymphatic duct may be involved in the resorption of
      endolymph.

PMID- 8749199
TI  - Auditory cortex neurons: primary culture and ion channel activity in rat.
AB  - We have developed a primary dissociated cell culture of the fetal (E17) and post
      natal (P0-P10) rat auditory cortex. Pyramidal and non-pyramidal cells had a mean
      cross-sectional diameter of 12.73 +/- 1.80 microns (mean +/- S.D., n = 25) and
      17.58 +/- 1.67 microns (mean +/- S.D., n = 10), respectively, measured at 6 days
      in culture. These cells were viable for as long as 18-21 days. They expressed
      voltage-gated sodium and potassium channel currents as early as one day in
      culture, and at various phases in cell culture. Sodium current, activated at
      membrane potentials more positive than -60 mV, displayed fast activation and
      inactivation kinetics. Fifty percent inactivation of sodium channels occurred at
      a pre-pulse potential of -63 mV. Delayed rectifier potassium channels were
      activated at potentials positive to -40 mV. Large hyperpolarizing constant
      current pulses elicited anode break action potentials, and large depolarizing
      constant current pulses exhibited rectification indicative of the delayed
      rectifying potassium channel activity.

PMID- 8749200
TI  - Racial considerations in acoustic neuroma removal with hearing preservation via
      the retrosigmoid approach.
AB  - Racial differences in the size, shape and structure of the cranium exist. This
      paper evaluates the importance of race in influencing the required sizes of
      craniotomies for gaining access to the lateral end of the internal auditory
      meatus without breaching the labyrinth via the retrosigmoid approach. Fine-cut CT
      scans of the temporal bones (axial cuts) of 34 Chinese and 34 Europeans were
      studied. The relevant distances and angles of the posterior cranial fossa and
      temporal bone were measured and statistically significant differences between the
      two races were found. This led us to the conclusion that a larger craniotomy is
      required in Europeans than in Chinese. In recommending an optimal size for a
      retrosigmoid craniotomy to remove acoustic neuromas completely and preserve
      hearing, the racial factor must be considered.

PMID- 8749201
TI  - Culture of rabbit middle ear epithelial cells. A method for primary culture and
      subculture with identification, characterization and growth specification.
AB  - During the last decade middle ear epithelium has been cultured from various
      species. Until now, subcultivation has been achieved only with the use of a
      feeder-cell layer or conditioned medium. These factors are possible confounders
      in the in vitro model. On the other hand, subcultivation is necessary for exact
      quantitative studies. We present a reproducible culture method allowing
      subcultivation without feeder-cells or conditioned medium. The main features in
      our method are a low-serum, hormone-supplemented medium, an incubation
      temperature of 34 degrees C, fixation of explants, gentle trypsinization and
      replating with high cell density. Cells were identified by immunohistochemistry
      through a battery of monclonal antibodies. The percentage of epithelial cells in
      the subculture was 99.2%. To our knowledge, this is the first report describing
      subcultivation of middle ear epithelial cells exclusively in a completely
      controlled environment. These are optimal circumstances for future investigation
      and quantification of various factors influencing proliferation and
      differentiation of middle ear epithelium.

PMID- 8749202
TI  - Antibodies to pneumolysin and pneumococcal capsular polysaccharides in middle ear
      fluid of children with acute otitis media.
AB  - Antibodies to pneumococcal pneumolysin and capsular polysaccharides were measured
      by enzyme immunoassay in 169 acute phase middle ear fluid samples of 116 children
      with acute otitis media. Antibodies to pneumococcal pneumolysin were detected in
      84% and to capsular polysaccharides in 50% of the MEF samples. The Ig class
      detected most often was IgA to both types of pneumococcal antigens, and it was
      present in MEF even with non-detectable levels of serum IgA of the same
      specificity. 59% of the MEF samples positive for IgA to pneumolysin were also
      positive for secretory component of the same specificity, and 53% of IgA to
      capsular polysaccharide pool (containing serotypes 6B, 14, 19F, and 23F),
      respectively. This suggests both leakage of specific IgA from serum to the middle
      ear and local production of it. In contrast, specific IgG was detected in MEF
      only with concomitant IgG in serum. Antibodies to pneumolysin occurred in no
      relation to bacterial findings in MEF. On the contrary, IgG class antibodies to
      capsular polysaccharides, most likely serum-derived, were detected less often in
      MEF samples positive for pneumococcus than for other bacteria.

PMID- 8749203
TI  - Cytokeratin expression patterns by one- and two-dimensional electrophoresis in
      pars flaccida cholesteatoma and pars tensa cholesteatoma.
AB  - Expression patterns of cytokeratins (CKs) in normal skin, in pars flaccida type
      cholesteatoma (PFTC), and in pars tensa type cholesteatoma (PTTC) were examined
      by means of one- and two-dimensional electrophoretic techniques. Both CKs 14 and
      5 pair (CKs 14/5) and CKs 10/1 were found in all materials. Neither CKs 16/6 nor
      19 was found in the skin. CKs 16/6 and 19 were both found in 3 out of 5 PFTCs,
      only CKs 16/6 in 1 out of 5 and neither CKs 16/6 nor 19 in 1 out of 5. CKs 16/6
      and 19 were both found in 1 out of 3 PTTCs, only CKs 16/6 in 1 out of 3 and
      neither CKs 16/6 nor 19 in 1 out of 3. There was no significant difference in the
      CKs expression patterns between PFTC and PTTC. The expression of CKs 16/6 and 19
      suggested that their matrix epithelia were hyperproliferative. However, not all
      of the cholesteatomas were always hyperproliferative. Patterns of the terminal
      differentiation of CKs 1, 5, 10 and 14 in the PFTC or the PTTC were basically the
      same as those in the skin. In the cholesteatoma, eack CK gradually diminished in
      molecular weight in the cornified layer and debris. Desmosomal proteins were
      abundant in skin but not in cholesteatomas.

PMID- 8749204
TI  - Limitations of acoustic rhinometry determined by a simple model.
AB  - To determine the accuracy of a commercially available transient signal acoustic
      rhinometer we constructed simple models from tubing of known dimensions. A series
      of models was constructed in which the main cylinder was constant whilst the
      aperture of an included constricted area was varied from 0.07 cm2-0.95 cm2. The
      area reconstruction for each model was then compared with the true area. Two
      parameters based on those used in clinical practice of acoustic rhinometry were
      employed to evaluate the error. The results demonstrate that the measurement of
      both the volume beyond a constriction and the area of the constriction may be
      associated with systematic errors. The reconstructed profile of each model is
      similarly erroneous. As the nose presents a proximal constriction, these findings
      are of considerable relevance to the clinical use of acoustic rhinometry.

PMID- 8749205
TI  - Acoustic rhinometry in the pre-operative assessment of adenoidectomy candidates.
AB  - Claims have been made for the potential of acoustic rhinometry (AR) in the
      evaluation of adenoidectomy patients. Little evidence has been presented to
      support such claims, and evidence is accumulating that AR is inaccurate in
      reflecting anatomical reality in the nasopharynx. We set out to establish whether
      acoustic rhinometry studies could predict operative decision-making sufficiently
      for it to be of assistance to the clinician, despite these theoretical and
      practical obstacles. A total of 101 patients aged 2-13 years were examined by AR
      using the impulse technique. Parameters were chosen from the area-distance
      function to indicate nasopharyngeal volumes and areas (decongested and non
      decongested). This information was compared with findings at EUA (examination
      under anaesthesia-obstruction categories: A-'good airway' to D-'severe
      obstruction'), operative decision (2 categories-'obstructive' = remove, versus
      'non obstructive' = leave in situ) and parents' symptom scores. Twenty-one
      patients were also evaluated post-operatively. There was considerable overlap
      between the AR parameters in the groups classified at EUA as 'obstructive' or
      'non obstructive', but this overlap diminished after decongestion. Logistic
      regression demonstrated that the decongested volume and area parameters were of
      significant predictive value with respect to operative decision (odds ratio for
      unit change in volume = 0.82; 95% C.I. = 0.70-0.97; p = 0.018). Parents' analogue
      scores for snoring and for [snoring+obstruction+ mouthbreathing] were also of
      significant predictive value. The presence of rhinitis diminishes the predictive
      value of AR. Acoustic rhinometry has potential as a pre-operative evaluation of
      the nasopharyngeal airway in adenoidectomy candidates, but the predictive value
      is low unless combined with clinical factors.

PMID- 8749206
TI  - Nitric oxide synthase in rat nasal mucosa; immunohistochemical and histochemical
      localization.
AB  - The localization of nitric oxide synthase (NOS) and its cofactor, nicotinamide
      adenine dinucleotide hydrogen phosphate (NADPH)-diaphorase, was examined in the
      nasal mucosa of the rat by immunohistochemical and histochemical methods. In
      addition to cryostat sections, whole mount preparations were used to examine the
      distribution of nerves. Both in the nasal mucosa and in associated ganglia, the
      distribution of NOS-immunoreactive nervous structures essentially corresponded to
      that of NADPH-diaphorase-positive ones. The NOS-immunopositive nerve fibers in
      the respiratory area of the nasal mucosa were distributed around blood vessels
      and in submucosal glands. Part of the respiratory area was supplied with
      intraepithelial arborizations of the immunopositive fibers. The epithelial cells
      in the respiratory area were NADPH-diaphorase positive but NOS immunoreactivity
      negative. In the olfactory area, the NADPH-diaphorase- and NOS-positive nerve
      fibers were restricted to blood vessels located deep in the submucosa. Throughout
      the nasal mucosa, arterial endothelium was NADPH-diaphorase positive but NOS
      immunoreactivity negative. Both NOS immunoreactivity and NADPH-diaphorase
      activity were found in major populations of neuronal somata in the sphenopalatine
      ganglion. The present study provides the direct evidence supporting the notion
      that nitric oxide is richly produced in autonomic nerves of the nasal mucosa
      derived from the sphenopalatine ganglion.

PMID- 8749207
TI  - Langerhans cells in normal and pathological vocal cord mucosa.
AB  - The Langerhans cells in samples of histologically normal and pathological vocal
      cord mucosa were counted after identification using S-100 polyclonal antibody.
      Langerhans cells were commonly seen in vocal cord polyp epithelium but were
      infrequent in normal cord mucosa. They were also identified in samples of
      squamous carcinoma, severe dysplasia and chronic inflammation.

PMID- 8749208
TI  - Prognostic factors for head and neck tumor recurrence.
AB  - The introduction of new treatment methods has stimulated the identification of
      further prognostic factors capable of defining the clinical and biological
      characteristics of the tumor type in question and improving treatment
      programming. The aim of this study was to identify which characteristics of the
      host and tumor are of prognostic value in relation to the onset of locoregional
      tumor recurrence. A total of 396 patients were studied. The tumor site
      distribution can be summarized as follows: 267 laryngohypopharyngeal, 74
      oropharyngeal, 55 oral cavity. Variables regarding patient, tumor and histology
      were evaluated for the purpose of analysis. Multivariate analysis of these
      prognostic factors was performed using PLR software by BMDP. Mean tumor
      recurrence time was 19 months. Seventeen of the 29 variables analysed did not
      influence the probability of tumor recurrence. Two variables reduced the risk of
      tumor recurrence: age > 61 years and abundant and prevalently lymphocytic intra
      and peritumoral infiltrate. The study of tumor recurrence onset mechanisms is
      justified by its impact on the evolution of disease. The use of multivariate
      analysis in this study showed that some clinical and pathological characteristics
      of squamous cell carcinoma of the head and neck have a statistically significant
      impact on tumor recurrence.

PMID- 8749209
TI  - The role of aortic, iliac and femoropopliteal endarterectomy in vascular surgery
      today.

PMID- 8749210
TI  - To dress or not to dress surgical wounds? Patients' attitudes to wound care after
      major abdominal operations.
AB  - OBJECTIVE: To find out what patients' attitudes were to wound care after
      abdominal operations to ensure that patients' own views were not violated by
      introducing a new method of wound care. DESIGN: Randomised study. SETTING:
      University hospital, Sweden. PATIENTS: 68 consecutive patients operated for
      benign gastrointestinal disease. INTERVENTIONS: Patients were randomised to have
      their abdominal wounds dressed or exposed. On their last day in hospital their
      attitudes were assessed by visual analogue score and questionnaire. MAIN OUTCOME
      MEASURES: Attitudes to wound care. RESULTS: There were no differences between the
      two groups in any of the variables studied. The visual analogue scores for
      postoperative pain were higher than had been anticipated. CONCLUSION: Most
      patients do not mind whether their wounds are covered with a dressing or not
      after abdominal operations.

PMID- 8749211
TI  - Multiple system organ failure may be influenced by macrophage hypoactivation as
      well as hyperactivation--importance of the double challenge.
AB  - OBJECTIVE: To find out if an infective challenge caused by a burn followed by
      caecal ligation and puncture in mice caused more abnormalities of the immune
      response than burn alone or caecal ligation and puncture alone. DESIGN:
      Laboratory study. SETTING: University hospital, USA. MATERIAL: 80 male 7-8 week
      old A/J mice. INTERVENTIONS: Burn followed 10 days later by caecal ligation and
      puncture (n = 18), caecal ligation and puncture alone (n = 24), burn alone (n =
      20), and controls (n = 18). The mice had their spleens removed on day 11 (n = 28;
      6, 8, 8, and 6 in the respective groups), day 12 (n = 26; 6, 8, 6, and 6), and
      day 13 (n = 26; 6, 8, 6, and 6), and splenocytes and adherent cells were
      harvested for measurement of prostaglandin E2 (PGE2), interleukin 1 (IL-1),
      interleukin 2 (IL-2), interleukin 6 (IL-6), and tumour necrosis factor alpha (TNF
      alpha). MAIN OUTCOME MEASURES: Alterations in the production of the cytokines.
      RESULTS: After the double challenge (burn followed by caecal ligation and
      puncture) there were significant reductions in production of TNF-alpha and IL-6
      compared with caecal ligation and puncture alone (p < 0.05), burn alone (p <
      0.05), and controls (p < 0.05). These findings indicate that activation of
      macrophages was reduced after infection; production of TNF-alpha, IL-1, and IL-6
      by splenocytes stimulated by lipopolysaccharide was reduced. CONCLUSIONS: The
      differences do not seem big enough to indicate that mortality would be increased
      after caecal ligation and puncture alone. Only when there has been a previous
      injury (which resulted in hyperactivation of macrophages followed by a more
      pronounced hypoactivation) would mortality increase. In view of clinical trials
      with antiendotoxin and antiTNF antibodies that failed to improve survival in
      infected patients, we suggest that the mechanisms of the cellular immune response
      need further clarification.

PMID- 8749212
TI  - Hereditary breast cancer in Finnish women.
AB  - OBJECTIVE: To estimate the incidence of hereditary breast cancer seen in one
      Finnish hospital and to study the characteristics of the disease. DESIGN:
      Retrospective questionnaire and study of Finnish Cancer Registry. SETTING:
      University hospital, Finland. SUBJECTS: All 669 patients operated on for breast
      cancer 1986-90. MAIN OUTCOME MEASURES: Type of breast cancer and morbidity in
      hereditary compared with other forms of breast cancer. The definition of
      hereditary breast cancer requires that at least three first degree relatives,
      inclusive of the proband, have breast cancer. RESULTS: Of the 669 patients 495
      answered the questionnaire. Ten patients (2%) were classified as having
      hereditary breast cancer. The remaining 485 patients had other types of breast
      cancer by definition. Of those that were not hereditary 89 (18%) were classified
      as having familial breast cancer. Of the 495 patients 396 (80%) were classified
      as sporadic. The mean age of the patients at onset of the disease was 56 years in
      the hereditary group, 55 years in the familial group, and 57 years in the
      sporadic group. One patient (10%) in the hereditary, five (6%) in the familial,
      and 17 patients (4%) in the sporadic group had bilateral disease. Ductal
      carcinoma was most common in all groups of patients with breast cancer.
      CONCLUSION: There were no statistical differences in this series in the age at
      onset, incidence of bilateral disease, stage, and histopathology among the
      groups, although bilateral and lobular cancer were seen more often in the group
      with hereditary breast cancer.

PMID- 8749213
TI  - Factors that influence the operative mortality after blunt hepatic injuries.
AB  - OBJECTIVE: To analyse causes of death and possible factors that influenced the
      operative mortality in patients with blunt hepatic injuries. DESIGN:
      Retrospective case study. SETTING: Medical center, Taiwan. PATIENTS: 109 adult
      patients with blunt hepatic injuries were treated surgically over the four year
      period from September 1987 to August 1991. MAIN OUTCOME MEASURE: Mortality.
      RESULTS: 36 patients (33%) had hepatorrhaphy or no repair, complex repairs were
      done for 73 patients (67%) and the overall mortality was 22% (24/109). Of those
      deaths, however, 4 were not liver-related, giving us a liver-related mortality of
      19% (20/105). Fourteen of the liver-related deaths occurred within 24 hours of
      injury of hemorrhagic shock or coagulopathy. Six occurred after 24 hours of
      sepsis and multiple system organ failure. Multivariate analysis showed that
      higher initial aspartate aminotransferase (AST) and Injury Severity Score as well
      as increasing operative blood loss resulted in a worsening prognosis. CONCLUSION:
      The initial AST activity and Injury Severity Score as well as the total operative
      blood loss were the significant factors that influenced the operative mortality
      after blunt hepatic injuries in our study. Prompt, expeditious, and appropriate
      surgical management to control operative loss is the only way for the surgeon to
      reduce the mortality of blunt hepatic injuries.

PMID- 8749214
TI  - Effects of pneumoperitoneum on splanchnic hemodynamics: an experimental study in
      pigs.
AB  - OBJECTIVE: To study the effects on splanchnic haemodynamics of pneumoperitoneum
      induced by carbon dioxide insufflation. DESIGN: Controlled experimental study.
      ANIMALS: 11 Pigs weighing 19-30 kg. INTERVENTION: The animals were divided into a
      control group (n = 4) and a experimental group (n = 7). Experimental animals were
      subjected to stepwise increasing intra-abdominal pressure from 0 mm Hg to 25 mm
      Hg by carbon dioxide insufflation. MAIN OUTCOME MEASURES: Portal venous blood
      flow, portal venous blood pressure, portal/hepatic vascular resistance, and
      gastrointestinal vascular resistance. RESULTS: At 25 mm Hg portal venous blood
      flow was reduced (66% of baseline), and portal venous blood pressure and
      portal/hepatic vascular resistance were increased (360% and 650% of baseline,
      respectively). The increase in gastrointestinal vascular resistance was less
      pronounced. CONCLUSIONS: Increased intra-abdominal pressure caused significant
      changes in the splanchnic haemodynamics. The risk was greater if the intra
      abdominal pressure exceeded 15 mm Hg.

PMID- 8749215
TI  - Follow-up after colorectal cancer: current practice in The Netherlands.
AB  - OBJECTIVE: To assess the current practice of follow-up after operations for
      colorectal cancer in The Netherlands in comparison with other countries. DESIGN:
      Postal survey. SETTING: All surgical departments in The Netherlands. MAIN OUTCOME
      MEASURES: Attitudes of surgeons towards detection and treatment of recurrences
      after colorectal cancer. RESULTS: Of the 139 questionnaires sent out, 136 (98%)
      were returned. History taking, physical examination, and colonoscopy for local
      recurrence and metachronous tumours were used by 90% of the hospitals. Attitudes
      towards screening for hepatic and pulmonary metastases and regional recurrence
      varied considerably between hospitals. Similar findings were found in seven
      surveys from other countries. CONCLUSION: There is no consensus among surgeons
      regarding the follow-up of patients with colorectal cancer. Randomised controlled
      trials comparing different follow-up strategies and cost-effectiveness analyses
      are needed to identify groups of patients that will benefit most from follow-up.
      Identification of these patients may lead to more agreement between surgeons.

PMID- 8749216
TI  - Anterior resection controls cancer of the rectum as well as abdominoperineal
      excision.
AB  - OBJECTIVE: To evaluate our results of anterior resection and abdominoperineal
      (AP) excision for the treatment of rectal cancer in terms of survival and local
      recurrence, and to assess the importance of clinical anastomotic leaks in the
      development of local recurrence. DESIGN: Retrospective study. SETTING: University
      hospital, Finland. SUBJECTS: 199 patients who underwent elective and curative
      operations for rectal cancer during the period 1981-1990. INTERVENTIONS: 83 AP
      excisions and 116 anterior resections. MAIN OUTCOME MEASURES: Five year survival
      and rate of local recurrence. RESULTS: The proportion of anterior resections
      increased (compared with AP excisions) significantly from 43% (40/94) in the
      period 1981-1985 to 72% (77/107) in the period 1986-1990, but five year survival
      did not change (71% and 68%, respectively). 81 patients (41%) developed
      recurrences, 56 (28%) of which were local and 40 (20%) were restricted to the
      pelvis. Local recurrence was significantly more common after AP excision (30/83,
      36%) than after anterior resection (26/116, 22%, p < 0.05). Advanced stage
      (Dukes' C) was a risk factor for local recurrence, but not the distance of the
      tumour from the anal verge. There were no significant differences between AP
      excision and anterior resection in patients with tumours in the distal two thirds
      of the rectum in terms of local recurrence (30/82, 37% compared with 14/62, 23%)
      and estimated overall five year survival (52/82, 63%, compared with 43/62, 69%).
      The corresponding figures for each stage were stage A, 19/21 (90%) compared with
      20/21 (95%); stage B, 23/34 (68%) compared with 21/24 (88%); and stage C, 10/27
      (37%) compared with 5/16 (31%). There were no significant differences between
      patients who developed clinical leaks (6/19, 32%) and those who did not (20/97,
      21%) by stage in proportion of patients free from local recurrence and survival
      at five years. CONCLUSION: The significantly increased number of anterior
      resections compared with AP excisions of the rectumin did not compromise our
      results in terms of local recurrence and five year survival, but did reduce the
      number of permanent colostomies.

PMID- 8749217
TI  - Endoluminal ultrasound and low-field magnetic resonance imaging are superior to
      clinical examination in the preoperative staging of rectal cancer.
AB  - OBJECTIVE: To compare digital examination, endoluminal ultrasound (ELU), and
      plain magnetic resonance imaging (MRI), with histopathological findings in the
      preoperative staging of rectal cancer. DESIGN: A prospective comparative study.
      SETTING: University hospital, Sweden. SUBJECTS: 35 patients with rectal cancer
      who presented during the period February 1987 to February 1991. RESULTS: The
      digital examination of 19 patients could be assessed and was correct in 13 (68%).
      ELU was done in 34 patients; the accuracy was 88%. Extension of tumour was
      overestimated in two and underestimated in two. MRI was done for 35 patients with
      an accuracy of 66%; in 12 patients extension was underestimated. The diagnostic
      accuracy of the assessment of lymph node involvement was 71% with ELU, and 72%
      with MRI. CONCLUSION: These findings indicate that MRI seems to underestimate the
      extension of rectal tumours, but both ELU and MRI can be helpful in selecting
      patients with advanced tumours for whom preoperative adjuvant treatment is being
      considered. ELU is superior in staging tumours confined to the rectal wall, and
      could be of value in the selection of patients whose tumours were suitable for
      local excision. None of these techniques, however, can reliably identify the
      extent of lymph node involvement.

PMID- 8749218
TI  - Large incisional hernias: a technique using a new aponeurotic overlap and
      prosthesis.

PMID- 8749219
TI  - Aggressive angiomyxoma of the pelvis and perineum: case report.

PMID- 8749220
TI  - Two giant bronchial aneurysms: effect of preoperative embolisation. case report.

PMID- 8749221
TI  - Endovascular treatment with microcoils of traumatic haemobilia: case report.

PMID- 8749222
TI  - Cardioprotective effects of selective inhibition of the two complement activation
      pathways in myocardial ischemia and reperfusion injury.
AB  - The complement (C) system-mediated neutrophil activation, adhesion to the
      coronary endothelium and accumulation into cardiac tissue are key steps in the
      pathogenesis of myocardial ischemia-reperfusion (MI/R) injury. We examined the
      differential role of the classical and the alternative complement pathway in MI/R
      injury in vivo. Rats were subjected to 20 min of myocardial ischemia followed by
      24 h of reperfusion. Either a classical pathway inhibitor [C1 esterase inhibitor
      (C1-INH) (15 mg/kg)] or an alternative pathway inhibitor soluble complement
      receptor 1 (sCR1)[des-LHR-A](15 mg/kg) or their vehicle were administered
      intravenously 1 min prior to reperfusion, and myocardial necrosis (creatine
      kinase loss) and neutrophil accumulation, cardiac myeloperoxidase activity, were
      examined. C1-INH significantly attenuated cardiac creatine kinase loss compared
      to MI/R rats given only vehicle (p < 0.05) 24 h after reperfusion. An alternative
      pathway inhibitor, sCR1 [des-LHR-A] attenuated myocardial injury to a lesser
      extent, although it was not significantly different from the value for C1-INH or
      vehicle. Besides cardiac myeloperoxidase activity, the ischemic cardiac tissue
      was significantly attenuated by both C1-INH and sCR1[desLHR-A] (p < 0.05 vs.
      vehicle). Both the classical and alternative pathways may contribute to MI/R
      injury via a neutrophil-dependent mechanism in vivo. Selective inhibition of the
      classical pathway of complement activation seems to be slightly more effective in
      limiting necrotic MI/R injury than the selective alternative pathway inhibition
      in this 24 h model of reperfusion injury, but equal doses of each inhibitor
      attenuated neutrophil accumulation.

PMID- 8749223
TI  - Ultrastructural changes of the myocardial and striated muscle following a
      challenge of normobaric hyperoxia: the protective effects of alpha-tocopherol.
AB  - Normobaric hyperoxia has known deleterious effects on survival, presumably due to
      the generation of superoxide anion and hydrogen peroxide. To investigate the
      anatomical substrate of the effect of normobaric hyperoxia on the myocardial and
      striated muscles and the protective effect, if any, of alpha-tocopherol (vitamin
      E) on these tissues, we administered 95-99% O2 to adult male Wistar rats for 24,
      48, 60 and 72 h. The animals were divided into four groups: 1) control I: six
      rats which breathed room air were used as controls for the ultrastructural
      studies; 2) control II: 10 rats which breathed 95-99% of O2 for up to 72 h were
      used as controls for arterial pressure, blood gases/pH, PvO2 and Hb measurements;
      3) group A: hyperoxia: 24 rats divided into four subgroups according to the time
      of exposure to hyperoxia, A24, A48, A60, A72; and 4) group B: alpha
      tocopherol/hyperoxia: 24 rats treated with alpha-tocopherol, 15 mg/kg/day, for 14
      days before the beginning and throughout the period of hyperoxia, were divided
      into four subgroups (B24, B48, B60, B72) according to the time of exposure to
      hyperoxia. Our results showed that: 1) up to the 60th hour, arterial pressure
      (MAP) was satisfactory; PaO2 > 280 mmHg; PaCO2, pH and Hb were within normal
      limits; 2) ultrastructural studies of the myocardial apex, the diaphragm and the
      quadriceps femoris showed dilatation of the sarcoplasmic reticulum/T-tubuli
      system, swelling of mitochondria, and structural derangement of myofibrils, in
      particular in the z-bands. The findings were proportionally related to the time
      of exposure of hyperoxia. They were also more intensely shown on myocardial and
      diaphragmatic fibers in group A; 3) the survival time (mean +/- SD) was 63.8 +/-
      2.5 h in group A and 68.9 +/- 3.8 h in group B. These results suggest that
      normobaric hyperoxia exerts a cytotoxic effect on the myocardial and striated
      muscle fibers and that the administration of alpha-tocopherol may delay or change
      the development of oxygen toxicity.

PMID- 8749224
TI  - Effects of K-ATP blocking guanidine diuretics during experimental kaliuresis in
      rats and dogs.
AB  - Several guanidine diuretics related to the renal tubular K-ATP blocker U-37883A
      were compared to standard diuretics under high K+ excretion conditions. In
      conscious rats, oral KCl(0.28 mEq) increased K+ excretion 3-fold. This kaliuresis
      was further enhanced by oral diuretic doses of ethoxzolamide (1 and 2 mg/kg),
      hydrochlorothiazide (HCTZ; 0.3 and 0.9 mg/kg), and furosemide (18 mg/kg), but was
      significantly blunted by oral triamterene (1 and 10 mg/kg). By comparison,
      diuretic doses of U-37883A and analogs U-18177 (10 and 30 mg/kg) and U-38658A (3
      and 9 mg/kg) did not affect K+ excretion. In conscious dogs, oral U-18177A (10
      mg/kg) and HCTZ (1 mg/kg) were compared during 3- to 13-fold kaliuresis induced
      by oral isotonic saline (200 mL), oral KCl (30.8 mEq), subcutaneous
      deoxycorticosterone acetate (1.0 mg/kg), and oral acetazolamide (20 mg/kg). HCTZ
      was diuretic and further increased K+ excretion and its fractional clearance by
      42 and 34%, respectively. Conversely, U-18177A was diuretic and slightly reduced
      these kaliuretic parameters by 11 and 20%. Thus, the guanidines U-18177 and U
      37883A exert a relatively eukalemic diuresis under normal and high K+ excretion
      conditions, and their putative renal tubular K-ATP blocking action seems an
      effective means of inducing diuretics with less K+ imbalance than with standard
      diuretics.

PMID- 8749225
TI  - Intravenous administration of cholecystokinin (CCK) stimulates prolactin and
      growth hormone release in the pig.
AB  - Blood samples were taken from prepubertal pigs (n = 7) surgically prepared with
      venous catheters before, and at intervals during the 30 min period after,
      administration of physiological saline (vehicle) or sulphated cholecystokinin
      octapeptide (CCK) (0.3, 0.7 and 1.3 mu g/kg). Plasma concentrations of prolactin
      and growth hormone were measured by radioimmunoassay. Statistically significant
      dose-related increases in prolactin occurred mainly in the first 10-min period
      following CCK administration. The peptide also stimulated growth hormone
      secretion although in a less consistent manner, with the increases tending to
      occur over a longer time period. Together with earlier reports showing that CCK
      induces cortisol release in pigs, these results suggest that the peptide's effect
      on anterior pituitary function could be indicative of a stress response.

PMID- 8749226
TI  - Pharmacokinetics of oral ketorolac in the rat.
AB  - The pharmacokinetics of ketorolac, a potent analgesic agent used for relief of
      moderate to severe pain, has been studied in rats who received oral doses of 1,
      3.2 or 5.6 mg/kg of ketorolac tromethamine. Blood samples were obtained at
      selected times during 24 h after medication, and ketorolac concentrations were
      determined by high performance liquid chromatography. After administration of
      ketorolac, blood concentrations increased rapidly reaching a dose-dependent
      maximal concentration in about 20 min. Then, concentrations decayed with a half
      life of about 6 h. A linear increase in Cmax and AUC as a function of the dose
      was observed, and not statistically significant difference was observed in
      AUC/dose or Cmax/dose between doses, indicating that pharmacokinetics of
      ketorolac is linear in the range of doses studied.

PMID- 8749227
TI  - Methylcobalamin treatment of Bell's palsy.
AB  - Sixty patients with Bell's palsy were included in an open randomized trial.
      Patients were assigned into three treatment groups: steroid (group 1),
      methylcobalamin (group 2) and methylcobalamin + steroid (group 3). Comparison
      between the three groups was based on the number of days needed to attain full
      recovery, facial nerve scores, and improvement of concomitant symptoms. The time
      required for complete recovery of facial nerve function was significantly shorter
      ( p < 0.001) in the methylcobalamin (mean of 1.95 +/- 0.51 weeks) and
      methylcobalamin plus steroid groups (mean of 2.05 +/- 1.23 weeks) than in the
      steroid group (mean of 9.60 +/- 7.79 weeks). The facial nerve score after 1-3
      weeks of treatment was significantly more severe (p < 0.001) in the steroid group
      compared to the methylcobalamin and methylcobalamin plus steroid groups. The
      improvement of concomitant symptoms was better in the methylcobalamin treated
      groups than the group treated with steroid alone.

PMID- 8749228
TI  - Treatment of hypertensive venous leg ulcers with nifedipine.
AB  - The effect of nifedipine in the treatment of hypertensive venous leg ulcers was
      studied on 30 outpatients in a double-blind placebo-controlled trail over a
      period of 2 months. The dose of nifedipine or the matching placebo was 10 mg 3
      times daily. Most of the subjective symptoms such as pain, paraesthesia and
      cramps at night considerably improved during the treatment with nifedipine and
      were slightly affected in the placebo group. The ulcer surface area decreased
      after 2 months treatment with nifedipine by 26.9% (p < 0.05), and after treatment
      with placebo by 8.6% (p > 0.05). An improvement of the photopletysmographic
      record of the lower legs in the nifedipine group was observed, demonstrated by an
      increase of the index recovery time (by 36.1%, p < 0.05), while there were no
      significant changes in the placebo group. The results show favorable effect of
      nifedipine in the treatment of hypertensive venous leg ulcers which might be due
      to a great extent to improvement of the subcutaneous circulation of the lower
      legs. Nifedipine may be an important adjunct to the conservative management of
      the complications caused by chronic venous insufficiency and hypertension.

PMID- 8749229
TI  - Lithium-pilocarpine neurotoxicity: a potential model of status epilepticus.
AB  - Convulsive status epilepticus (SE) is clinically defined as prolonged electrical
      and clinical seizure activity in which the patient does not regain consciousness
      to a normal alert state between repeated tonic-clonic attacks. The disorder is a
      neurological emergency associated with a mortality rate of 10-12% and an even
      greater morbidity. Seizures represent one of the most severe in vivo stimulatory
      stresses that the brain is exposed to and generalized status epilepticus
      represents a very severe form of seizures. The International Classification of
      Seizures has defined this condition as "a condition characterized by an epileptic
      seizure that is so frequent or so prolonged as to create a fixed and lasting
      condition". During SE, high-amplitude, high-frequency electrical activity lasting
      at least 5 min is seen in the EEG. Continuous seizure activity in itself will
      result in progressive brain injury. The longer the condition of SE, the more
      difficult it is to control and the more likely it is to result in permanent
      neuronal damage. Therefore, SE is an emergency situation requiring prompt medical
      attention if severe permanent brain damage or death is to be prevented. SE often
      occurs in individuals with a history of seizures, in whom there are neural
      substrates already predisposed towards supporting seizure activity.

PMID- 8749230
TI  - Cell surface-bound urokinase-type plasminogen activator facilitates infiltration
      of freshly isolated granulocytes into fibrin matrix.
AB  - Human cell lines of myelo/monocytic origin express the cellular receptor for
      urokinase-type plasminogen activator (uPA-R). The receptor localizes urokinase
      type plasminogen activator (uPA) to the surface of the cell, where it can convert
      plasminogen to the active serine proteinase plasmin. Plasmin may subsequently
      account for proteolysis of pericellular proteins. We demonstrated the expression
      of the uPA-R by freshly isolated neutrophilic granulocytes by using a specific
      mAb. In freshly isolated granulocytes we detected only a weak occupation of the
      uPA-R; further uPA binding by granulocytes was saturable and proceeded in a dose
      dependent manner. Receptor-bound uPA retained its enzymatic activity. Saturation
      of isolated granulocytes with exogenous uPA enhanced cellular infiltration into a
      fibrin matrix in vitro. uPA-dependent infiltration was inhibited by an anti
      catalytic monoclonal anti-uPA antibody. The findings show that circulating
      neutrophilic granulocytes express the cell surface uPA-R and suggest that surface
      binding of uPA may facilitate the infiltration of granulocytes into a fibrin
      clot, a process that might add to thrombolysis in vivo.

PMID- 8749231
TI  - Development of insulin-dependent diabetes mellitus in [(NOD + BALB/c) --> NOD]
      mixed allogeneic bone marrow chimeras.
AB  - To examine the possibility that the bone marrow cells of BALB/c genotype
      interfere with the development of insulitis and diabetes in NOD mice, we
      transplanted BALB/c bone marrow cells mixed with NOD bone marrow cells into NOD
      mice. The [(NOD + BALB/c) --> NOD] chimeras developed insulitis and diabetes,
      indicating that BALB/c bone marrow cells do not interfere with the development of
      the disease in NOD mice. Surprisingly, these mice have been reconstituted with
      only NOD hematolymphoid cells. When the pancreatic tissues from newborn NOD and
      BALB/c mice were grafted into [(NOD + BALB/c) --> NOD] chimeras, the BALB/c
      pancreatic tissues were rejected, whereas the NOD graft showed insulitis.
      Furthermore, the spleen cells of the chimeras showed responsiveness to BALB/c
      spleen cells in mixed lymphocyte reaction and generated cytotoxic T lymphocytes
      specific for the H-2d and third party targets. These findings indicate that the
      hematolymphoid cells (including hemopoietic stem cells) of NOD mice are more
      resilient than those of normal BALB/c mice, and that insulin-dependent diabetes
      mellitus will recur after bone marrow transplantation unless the hematolymphoid
      cells of NOD mice are completely destroyed by irradiation.

PMID- 8749232
TI  - Retrovirus-induced lymphoproliferative disease in mice: role of humoral immunity
      in perinatally exposed mice.
AB  - The mice born to female mice infected with LP-BM5 MuLV, the etiologic agent for
      lymphoproliferative disease and nursed for 4-6 weeks by them were less
      susceptible upon reinfection by i.v. transfusion of blood or plasma from infected
      donors with fully developed disease. Sera of 7 week or older perinatally exposed
      mice were capable of a complete in vitro neutralization of virus in plasma or
      blood from mice with fully developed disease. In contrast, sera from 3-week old
      perinatally exposed mice were ineffective. The neutralizing ability of the sera
      was drastically reduced or abrogated after their absorption with anti-mouse IgM.
      These observations are consistent with the notion that perinatally exposure
      results ina moderate form of the disease of the offspring. This perinatal
      infection is followed by a production of neutralizing antibodies of predominantly
      the IgM class that significantly alters the course of the lymphoproliferative
      disease and, in some instances, even prevents its development.

PMID- 8749233
TI  - Oral tolerance is determined at the level of draining lymph nodes.
AB  - In the skin and in the epithelium of the oral mucosa a comparable network of
      Langerhans cells can be found. Antigen application on either epithelium leads to
      rapid emigration of Langerhans cells to the draining lymph nodes. Application on
      the oral mucosa leads to tolerance induction while application on the skin
      results in sensitization of the animal. Here we show that there are no
      differences in the antigen presentation capacity of oral mucosa- and skin-derived
      dendritic cells. However, measurement of IFN-gamma and IL-5 production, as
      representatives of Th1 and Th2 cytokines respectively, in total lymph node
      suspensions after sensitization via the skin or oral mucosa demonstrated a
      skewing of the response towards Th2 after antigen application on the oral mucosa.
      Together with our previous studies, in which it was shown that oral tolerance
      induction is not inherent to oral mucosa-derived dendritic cells, we postulate
      that oral tolerance is determined at the level of draining lymph nodes influenced
      by local cytokine profiles.

PMID- 8749234
TI  - Oxysterol-induced apoptosis in human monocytic cell lines.
AB  - Oxysterols constitute a large family of natural compounds, endowed with various
      biological activities including cholesterol regulation, immunosuppression and
      antitumoral potency. In the present study, we examine and compare the cytotoxic
      effects of two representative members of this family: 7 beta-hydroxycholesterol
      (7 beta-OH) and 25-hydroxycholesterol (25-OH), in two human monocytic cell lines,
      U-937 and HL-60. In both cell lines 7 beta-OH at 30 mu M induces cell death by
      apoptosis within the first hours of treatment. Under the same conditions and in
      contrast with results previously obtained with lymphoma cells, 25-OH is
      cytostatic only. It is interesting to note that the simultaneous treatment of U
      937 cells by equimolar concentrations of 7 beta-OH and 25-OH leads to a
      considerably decreased induction of apoptosis. Such an effect is not observed
      with HL-60 cells. Taken together, these results indicate for the first time that:
      1) oxysterols hydroxylated on the sterol nucleus are also able to induce
      apoptosis, 2) apoptosis can be induced by these substances in cells belonging to
      the myeloid lineage and 3) as far as apoptosis is concerned, a combined treatment
      with 7 beta-OH and 25-OH can lead to opposite effects depending on the cell type.

PMID- 8749235
TI  - Is CD26/dipeptidyl peptidase IV a really important molecule in T cell activation
      of a certain rat strain?
AB  - A new monoclonal antibody (MS-7 mAb) was raised to investigate the real role of
      the membrane-associated molecule CD26/dipeptidyl peptidase IV (DPP IV; EC
      3.4.14.5), which transduces activation signals in T cells. A strain of rats which
      is deficient in DPP IV was used. MS-7 mAb recognized DPP IV (110 kDa) and its 60
      kDa fragment, starting at the 281st residue corresponding to the extracellular
      one comprising the active-site sequence Gly-X-Ser631-X-Gly of DPP IV. MS-7 mAb
      recognized CD26 on T cells of DPP IV+ rats both before and after mitogen
      activation. CD26 expression and DPP IV enzyme activity are increased on T cells
      following their activation; nevertheless, no CD26 was expressed on T cells of DPP
      IV- rats, and no DPP IV enzyme activity was detected either before or after
      mitogen activation. In addition, MS-7 mAb inhibited the mitogen-stimulated
      proliferation of DPP IV+ rats, but did not affect that of DPP IV- rats. These
      results suggest that CD26/DPP IV is not a necessary molecule in T cell
      activation, and that there is some other bypass in T cell activation of DPP IV-
      rats.

PMID- 8749236
TI  - Cleavage of the third component of complement (C3) by mannose-binding protein
      associated serine protease (MASP) with subsequent complement activation.
AB  - We have previously shown that a novel C1s-like serine protease termed MBP
      associated serine protease (MASP) is responsible for activation of the complement
      cascade initiated by mannose-binding protein (MBP). In this communication, we
      report that MASP is unique in having the proteolytic capacity to cleave C3 with
      subsequent activation of the alternative pathway, a capacity which C1s lacks.

PMID- 8749237
TI  - Differential MAGE-1 gene expression in two variants of an erythroleukemic cell
      line (K562).
AB  - The MAGE-1 gene encodes an antigen recognized on melanoma cells by autologous
      cytotoxic T cells. This gene shows a wide range of expression in many human
      tumors but not in normal tissues except for testes. We used reverse transcription
      polymerase chain reaction assays to analyze the expression of the MAGE-1 gene in
      two variants of an erythroleukemic cell line, K562. Comparison of two variants of
      the K562 cell line in different stages of differentiation showed different
      patterns of expression of the MAGE-1 gene. The more undifferentiated cell line
      (K562A) expressed high levels of specific MAGE-1 mRNA, in contrast to K562B,
      which features of erythroid differentiation, without MAGE-1 expression.
      Interestingly, we could not modulate MAGE-1 gene expression when in vitro
      differentiation of K562A was induced with Ara-C. Finally, our data indicate that
      MAGE-1 expression is not necessary for the maintenance of the transformed
      phenotype.

PMID- 8749238
TI  - The history of migraine from Mesopotamian to Medieval times.
AB  - The first descriptions of migraine can be traced back nearly 4,000 years from the
      ancient civilizations of Mesopotamia (Sumeria and Babylonia) through Egyptian,
      Greek and Roman epochs. Through Byzantine, Arabic and Medieval times there are
      only patchy references until the 17th century, when European physicians first
      gave full case reports.

PMID- 8749239
TI  - Migraine impact and functional disability.
AB  - This article reviews the substantial impact of migraine on individual headache
      sufferers and on society. While the individual impact of migraine is determined
      by pain and role dysfunction, the societal impact is primarily determined by work
      loss and disability in the work place and at home. Epidemiologic studies
      demonstrate that migraine is very common, substantially under diagnosed and often
      inadequately treated. Improving health care delivery to persons with migraine
      could substantially reduce the individual and societal impact of the illness.
      Migraine ranges in severity, with mild headache and no disability on one extreme
      and excruciating pain and complete disability on the other. Because of this
      spectrum of severity, diagnosis alone does not provide enough information to
      permit the selection of optimal therapy. A headache grading system might help
      headache sufferers and clinicians match the therapy not only to the diagnosis but
      to the overall severity of illness; such a system provides the best hope for cost
      effective health care interventions.

PMID- 8749240
TI  - Early-phase clinical trials in migraine: efficacy, safety and dose-finding.
AB  - Early-phase clinical trials with any new chemical entity have three main
      objectives: to establish that the drug is effective in the target disease and
      patient population; to assess tolerability and safety; and to select the optimum
      dose or doses for further evaluation. Clinical trials in migraine and other
      headache disorders pose additional problems because of the lack of specific
      objective diagnostic tests and the reliance on patient assessments of symptom
      relief. For these reasons particular care must be taken in selection of patients,
      design of the trials, choice of end-points and statistical analytical
      methodology. A wide range of doses must be evaluated to ensure that the dose
      response curves for both efficacy and safety/tolerability are fully defined.
      Successful early-phase trials should then allow the optimum dose or doses of the
      drug to be identified for further evaluation in large-scale outpatient studies.

PMID- 8749241
TI  - Analgesics and NSAIDs in the treatment of the acute migraine attack.
AB  - In the treatment of migraine attacks, an antiemetic in combination with an
      analgesic or ergot alkaloid is widely recommended. Medication should be
      introduced as early as possible, but only when there is no doubt that the
      headache is due to migraine. The antiemetic provides relief from the nausea and
      vomiting and also enhances the resorption of analgesics or ergot preparations.
      Domperidone 20 mg orally and 20 mg metoclopramide as suppository or 10-20 mg
      orally are mostly used as antiemetics. Analgesics such as 1000 mg acetylsalicylic
      acid as effervescent tablets, or 1000 mg paracetamol as effervescent tablets or
      suppositories should be given 15-20 min later. If this treatment fails, NSAIDs
      can be tried. In some studies naproxen in doses between 500 and 1000 mg and
      ibuprofen in doses between 400 and 800 mg have been shown to be effective, as
      well as NSAIDs like diclofenac, mefenamic acid, ketoprofen, tolfenamic acid and
      pirprofen. NSAIDs have been found to be superior to placebo and to standard
      reference drugs in the majority of the reviewed double-blind trials.
      Nevertheless, these effects are marginal in some studies or even without clinical
      relevance. Accordingly, there is still a need for further comparative studies.

PMID- 8749242
TI  - How does sumatriptan perform in clinical practice?
AB  - The patient's opinion on sumatriptan treatment has been obtained from 351
      migraineurs (299F and 52M) by means of a telephone survey. The results are based
      on the patient's cumulative experience of more than 20,000 subcutaneous
      injections and more than 2,000 tablet doses. The average period during which
      subcutaneous sumatriptan (12 mg/ml, 0.5 ml) was used was 19.1 +/- 0.4 months and
      84% of the patients had used more than 10 injections. The average number of
      migraine attacks per month was 3.0 +/- 0.1, injections per attack 1.7 +/- 0.1,
      and number of tablets (100 mg) per attack 1.8 +/- 0.2. Attack duration was
      decreased from on average 38.4 +/- 2.1 h to 2.3 +/- 0.5 h by subcutaneous
      sumatriptan and to 3.4 +/- 1.0 by orally administered sumatriptan. The average
      degree of efficiency at work with migraine was 76.3 +/- 1.9% on sumatriptan
      compared with 26.6% on other treatment options; 85% said that sumatriptan was
      much better than previous conventional therapies tested. During their experience
      with sumatriptan, 89% of the migraineurs reported altogether 1,058 adverse events
      (average 3.6 +/- 01, range 1 to 12) in connection with subcutaneous sumatriptan
      treatment. The three most frequent were drowsiness/sedation (49%), chest symptoms
      (40%) and injection site symptoms (37%). Among the table users, 87% reported
      altogether 122 adverse events (average 2.6 +/- 0.3, range 1 to 11). Seventy-eight
      percent of the responders responded to subcutaneous sumatriptan sometimes (22%
      always, 15% every second attack, 40% seldom) experienced a recurrence of their
      headache within 24 h. The average number of recurrences was 1.7 +/- 0.1 and the
      average time to recurrence 13.0 +/- 0.6 h (range 1.5-24 h). It is concluded that
      the selected group of migraineurs found sumatriptan to be very effective in
      reducing the symptoms of their migraine attacks, but also to cause several
      adverse events, in many cases, with short-lasting effect.

PMID- 8749243
TI  - Prophylactic treatment of migraine: evaluation of clinical trials and choice
      among drugs.
AB  - A checklist is presented to assist with the evaluation of a controlled trial in
      migraine prophylaxis. The following points are discussed briefly: aim of the
      study, design of the study, efficacy parameters, and presentation of results and
      statistics. Choice among drugs for migraine prophylaxis is described taking into
      account: clinical efficacy, scientific proof for efficacy, and contraindications.

PMID- 8749244
TI  - Treatment of cluster headache: clinical trials, design and results.
AB  - The spontaneous capricious course of cluster headache may give rise to some
      problems when treatment is being evaluated. This is one of several explanations
      for there being so few well-designed, randomized, double-blind clinical trials in
      cluster headache. The standard treatment of acute attacks of cluster headache is
      inhalation of 100% oxygen. In the prophylaxis of episodic cluster headache,
      ergotamine, verapamil, lithium, serotonin, inhibitors and steroids are used. In
      chronic cluster, lithium is the drug of choice, but verapamil may also be tried.
      Recently, hyperbaric oxygen has been shown to immediately abort acute attacks,
      and it seems that it may also be useful in the prophylactic treatment. The
      introduction of the novel 5HT1 agonist sumatriptan as a symptomatic relief of
      cluster attacks represents further significant progress. Two randomized, double
      blind, placebo-controlled, cross-over trials have shown sumatriptan 6 mg sc to be
      a rapid, effective and well-tolerated acute treatment for cluster headache
      attacks. Within 15 min of treatment, 74% of attacks on sumatriptan responded
      compared to 26% of placebo-treated attacks. Functional disability was also
      significantly improved. Increasing the dose to 12 mg did not offer significantly
      greater relief compared to sumatriptan 6 mg, but was associated with an increased
      incidence of adverse events. Interim analysis of 3 months of data from a recent
      multinational open trial comprising, 138 patients having treated 6353 attacks
      with subcutaneous sumatriptan 6 mg revealed a headache relief in 96% of attacks
      treated. There was no evidence of an increased incidence of adverse events with
      frequent use of sumatriptan. No tachyphylaxis was seen over the 3 months,
      suggesting that sumatriptan is effective and well tolerated also in long-term
      acute treatment for cluster headache.

PMID- 8749245
TI  - Long-term cost-benefit assessment of anti-migraine drugs.
AB  - Migraine, being disabling and common, is a costly illness. The bearers of the
      cost are a broader band of society than the sufferers from the disease, and the
      elements of the cost are not only monetary. Treatment of migraine has the
      potential for reducing this cost but carries a cost of its own. In the balance
      between these, those who pay are not necessarily the same as those who gain.
      Various forms of analysis are employed in relating illness costs at individual
      and societal levels with those of measures intended to contain them. Questions
      that arise are whether costs are saved overall by treatment, and which of
      different treatment options give greater savings. In the absence of much data,
      there is heavy dependence on assumptions in attempts to answer these questions. A
      full analysis should take into account the extent to which the availability of
      new and very effective treatments might alter demand and clinical practice, and
      also the impacts of ineffective use and inappropriate use of treatments.

PMID- 8749246
TI  - Chromatographic techniques--the basis of doping control.
AB  - The principal definition of doping, the groups of banned compounds and the basic
      analytical problems and strategy of doping analysis are outlined, and the
      position of chromatography in doping analysis is explained. Examples of the
      application of GC-MS, especially high-resolution MS. and of LC-thermospray MS to
      doping problems are given. A practical case is presented briefly, showing the
      post-analytical problem of evaluating even unequivocal results.

PMID- 8749247
TI  - Interaction of human immunoglobulin G with l-histidine immobilized onto
      poly(ethylene vinyl alcohol) hollow-fiber membranes.
AB  - L-Histidine as pseudobiospecific ligand was immobilized onto poly(ethylene vinyl
      alcohol) hollow-fiber membranes to obtain an affinity support for immunoglobulin
      G (IgG) purification. The interaction of human IgG with the affinity membranes
      was studied by chromatography and equilibrium binding analysis. Adsorption was
      possible over a broad pH range and was found to depend strongly on the nature of
      the buffer ions rather than on ionic strength. With zwitterionic buffers like
      morpholinopropanesulfonic acid (Mops) and hydroxyethylpiperazineethanesulfonic
      acid (Hepes), much higher adsorption capacities were obtained than with other
      buffers like Tris-HCl and phosphate buffers. An inhibition analysis revealed that
      non-zwitterionic buffers competitively inhibit IgG binding, whereas Mops and
      Hepes in their zwitterionic form do not. By choosing the appropriate buffer
      system, it was possible to adsorb specifically different IgG subsets. The IgG
      molecules were found to adsorb on membrane immobilized histidine via their Fab
      part. Determination of dissociation constants at different temperatures allowed
      calculation of thermodynamic adsorption parameters. Decrease in KD with
      increasing temperature and a positive entropy value between 20 and 35 degrees C
      (in Mops buffer) indicated that adsorption is partially governed by hydrophobic
      forces in that temperature range, whereas at lower temperatures, electrostatic
      forces are more important for adsorption.

PMID- 8749248
TI  - Effect of ageing on human plasma glutathione concentrations as determined by high
      performance liquid chromatography with fluorimetric detection.
AB  - A convenient method for the determination of reduced glutathione (GSH) and
      oxidized glutathione (GSSG) in human plasma by high-performance liquid
      chromatography with fluorescence detection is reported. This assay involves
      direct addition of human plasma to methanolic monobromobimane, for simultaneous
      protein precipitation and thiol derivatization. The assay was validated by
      addition of authentic GSH and GSSG to plasma samples. Plasma glutathione levels
      in Chinese male and female volunteers were found to decrease with increasing age
      (age groups 20-30, 30-40, 40-50, 50-60, and > 60; mean +/- S.E.M. 0.95 +/- 0.03,
      0.77 +/- 0.02, 0.67 +/- 0.03, 0.51 +/- 0.02, 0.48 +/- 0.02 microM for male
      volunteers and 1.11 +/- 0.06, 0.76 +/- 0.03, 0.61 +/- 0.03, 0.53 +/- 0.04 and
      0.43 +/- 0.04 microM for female volunteers). GSSG levels, in both males and
      females, did not show a correlation with age. There were no significant
      differences in GSH or GSSG levels among male and female volunteers of the same
      age group. These results suggest that elderly persons might be more susceptible
      to oxidative injury due to decreased plasma glutathione levels.

PMID- 8749249
TI  - Micellar electrokinetic capillary chromatographic separation of steroids in urine
      by trioctylphosphine oxide and cationic surfactant.
AB  - Separation of the six structurally similar and hydrophobic neutral steroids,
      testosterone, dimethyltestosterone, testosterone propionate, cortisone,
      hydrocortisone and 17-deoxycorticosterone, was achieved by hydrophobic micellar
      electrokinetic chromatography. A triphasic separation involving micellar
      dodecyltrimethylammonium bromide (DTAB), a dynamic bilayer formed due to
      electrostatic interaction between the silica surface and DTAB, and aqueous phase
      is proposed to account for the observed separation of the steroids. The running
      buffer consisted of 0.05 M DTAB and 0.0052 M trioctylphosphine oxide in 0.01 M of
      phosphate buffer pH 7.4. A detection limit of 500 ng/ml was achieved for each
      steroid and the application of the method to urine samples is described.

PMID- 8749250
TI  - Separation and characterization of red blood cells with different membrane
      deformability using steric field-flow fractionation.
AB  - Human red blood cells were treated in different ways to alter their membrane
      deformability, and the hydrodynamic behavior of these altered cells was studied
      using the steric field-flow fractionation (FFF) technique. The relationships
      between cell retention in the FFF channel, flow-rate of the carrier fluid and the
      applied field strength were studied for normal and glutaraldehyde-fixed human red
      cells, and separation conditions were optimized. The effect of flow-induced
      hydrodynamic lift forces on red cell retention in the steric FFF channel was
      studied, and the results suggest that the membrane deformability of the red cell
      is an important factor contributing to the lift force, besides other previously
      described effects due to density and flow velocity. Using steric FFF, a mixture
      of normal and glutaraldehyde-fixed human red cells was completely separated with
      a resolution twice that found in published data from gel permeation, another
      hydrodynamic separation technique. Partial loss of membrane deformability,
      induced by different degrees of glutaraldehyde-fixation, by diamide, or by a
      thermal treatment, has also been studied. Steric FFF is thus shown to have
      potential for rapid separation and differentiation of red cells with different
      density and membrane deformability, conditions known to be associated with, e.g.,
      cell senescence and certain hematological diseases.

PMID- 8749251
TI  - Determination of codeine and metabolites in plasma and urine using ion-pair high
      performance liquid chromatography.
AB  - A reversed-phase ion-pair high-performance liquid chromatographic method for the
      simultaneous determination of codeine and seven metabolites is described. The
      samples are purified by reversed-phase solid-phase extraction. Codeine,
      norcodeine, codeine-6-glucuronide, norcodeine-6-glucuronide and morphine-3
      glucuronide are measured with UV detection. Detection limits are 3 nmol/l
      (morphine-3-glucuronide) to 20 nmol/l (codeine). Morphine, normorphine and
      morphine-6-glucuronide are measured with electrochemical detection. Detection
      limits are 0.4 nmol/1 (morphine-6-glucuronide) to 1.0 nmol/l (normorphine).
      Correlation coefficients better than 0.998 are normally obtained for all
      compounds. The method was applied to the determination of the kinetics of codeine
      and its metabolites in plasma and urine samples from healthy volunteers.

PMID- 8749252
TI  - Rapid and highly automated determination of morphine and morphine glucuronides in
      plasma by on-line solid-phase extraction and column liquid chromatography.
AB  - A high-performance liquid chromatography (HPLC) method has been developed for the
      determination of morphine and its main metabolites, morphine-6-glucuronide (M-6
      G) and morphine-3-glucuronide (M-3-G), in plasma or cerebrospinal fluid. Samples
      were extracted using on-line solid-phase extraction followed by reversed-phase
      HPLC with fluorescence detection. Recoveries of 20 ng morphine and morphine
      glucuronides in plasma were over 95%. The limit of detection using 400
      microliters of a biological matrix was 0.85, 3.4 and 1.0 ng/ml of M-3-G, M-6-G
      and morphine, respectively. Inter- and intra-day assay precision was better than
      10%. The main advantages of the present described method are increased recoveries
      (> 95%) and a high degree of automation allowing a high speed in routine
      analysis. The time required for the fully automated analysis of one sample was
      less than 26 min.

PMID- 8749253
TI  - Sensitive fused-silica capillary gas chromatographic assay using electron-capture
      detection for indomethacin in ovine fetal fluids.
AB  - A sensitive gas chromatographic (GC) method with electron-capture detection (ECD)
      has been developed to quantitate indomethacin (IND) in plasma, urine, amniotic,
      and tracheal fluids obtained from the pregnant sheep model. IND and the internal
      standard, alpha-methylindomethacin (alpha-Me-IND) are extracted by a simple
      liquid-liquid extraction procedure using ethyl acetate and derivatized with N
      methyl-N-(tert.-butyldimethyl-silyl)trifluoroacetamide (MTBSTFA) at 60 degrees C
      for 50 min. The limit of quantitation (LOQ) is 1 ng/ml with a C.V. < 10% and
      signal-to-noise ratio > 10. Recoveries from all fluids were greater than 80%.
      Calibration curves were linear over the range of 1-32 ng/ml with a coefficient of
      determination (r2) > 0.999. Inter- and intra-day coefficients of variation were <
      10% at concentrations of 2-32 ng/ml, and < 20% at the LOQ. Applicability of the
      developed method is demonstrated for a pharmacokinetic study of IND samples
      collected following long-term infusion of IND in a chronically instrumented ovine
      fetus.

PMID- 8749254
TI  - Enantioselective determination of sotalol enantiomers in biological fluids using
      high-performance liquid chromatography.
AB  - A simple and sensitive high-performance liquid chromatographic (HPLC) method for
      the determination of (+)-(S)-sotalol and (-)-(R)-sotalol in biological fluids was
      established. Following extraction with isopropyl alcohol from biological samples
      on a Sep-Pak C18 cartridge, the eluent was derivatized with 2,3,4,6-tetra-O
      acetyl-beta-D-glucopyranosyl isothiocyanate (GITC). The diastereoisomeric
      derivates were resolved by HPLC with UV detection at 225 nm. Calibration was
      linear from 0.022 to 4.41 micrograms/ml in human plasma and from 0.22 to 88.2
      micrograms/ml in human urine for both (+)-(S)- and (-)-(R)-sotalol. The lower
      limit of determination was 0.022 microgram/ml for plasma and 0.22 microgram/ml
      for urine. The within-day and day-to-day coefficients of variation were less than
      7.5% for each enantiomer at 0.09 and 1.8 microgram/ml in plasma and at 0.44 and
      4.4 micrograms/ml in urine. The method is also applicable to other biological
      specimens such as rat, mouse and rabbit plasma.

PMID- 8749255
TI  - High-performance liquid chromatography with amperometric detection applied to the
      screening of beta-blockers in human urine.
AB  - A high-performance liquid chromatographic method with electrochemical detection
      has been developed for the determination of six beta-blockers: atenolol, nadolol,
      timolol, metoprolol, oxprenolol, and alprenolol. The chromatographic separation
      was performed using a mu Bondapack C18 column, a mobile phase of acetonitrile
      water (40:60), containing 5 mM KH2PO4/K2HPO4 proved to be optimal at a 1.3 ml/min
      flow-rate, and a pH of 6.5. The temperature was optimized at 30 +/- 0.2 degrees
      C. The amperometric detector, equipped with a glassy carbon electrode, was
      operated at 1300 mV versus Ag/AgCl in the direct current mode. The method was
      applied to the determination of these compounds at two concentration levels: ppm
      and ppb (ng/ml), obtaining relative standard deviations lower than 5% at ppm
      levels and lower than 10% at ppb levels, and quantitation limits ranging from 15
      ppb to 500 ppb. The method was applied to the screening of beta-blockers in
      spiked urine samples, with a total elution time lower than 12 min, obtaining the
      best recoveries for timolol and metoprolol (never greater than 93%). These
      recoveries together with the low limits of quantitation achieved, allows its
      application to doping analysis in human urine.

PMID- 8749256
TI  - Sensitive assay for measuring amoxicillin in human plasma and middle ear fluid
      using solid-phase extraction and reversed-phase high-performance liquid
      chromatography.
AB  - We developed a sensitive assay to measure amoxicillin in human plasma and middle
      ear fluid (MEF) using solid-phase extraction and reversed-phase HPLC. Amoxicillin
      and cefadroxil, the internal standard, were extracted from 50-200 microliters of
      sample with Bond Elut C18 cartridges. The extract was analyzed on a 15 cm x 2 mm,
      5 micron Keystone MOS Hypersil-1 (C8) column with UV detection at 210 nm. The
      mobile phase was 6% acetonitrile in 5 mM phosphate buffer (pH = 6.5) and 5 mM
      tetrabutylammonium. The average absolute recovery of amoxicillin and cefadroxil
      were 91.2 +/- 16.6% and 91.0 +/- 6.8%, respectively. The limit of quantitation
      was 0.125 microgram/ml with 200 microliters sample size. The linear range was
      from 0.125 to 35.0 micrograms/ml with correlation coefficients greater than
      0.999. These analytic conditions produced a highly sensitive amoxicillin assay in
      human body fluids without derivatization.

PMID- 8749257
TI  - Determination of methotrexate and 7-hydroxymethotrexate by liquid chromatography
      for routine monitoring of plasma levels.
AB  - A high-performance liquid chromatographic (HPLC) method was designed to meet
      analytical and metrological requirements for routine blood level monitoring of
      methotrexate (MTX) and its main metabolite 7-hydroxymethotrexate (7OMTX). The
      metabolite, unavailable as a pure substance, was measured by reference to MTX
      calibration according to their respective ultraviolet absorbances. Acetonitrile
      deproteinization and chloroform clean-up provided plasma samples devoid of long
      retained contaminants. The precision of the HPLC measurements, reproducibility of
      clean-up recovery, matrix effects and linearity were assessed by analysis of
      variance and linear regression in an appropriate experimental design, within a
      range from 0.205 to 16.7 mg/l of MTX and from 0.084 to 6.83 mg/l of 7OMTX. The
      clean-up recovery from plasma was 88% for MTX and 72% for 7OMTX, owing to
      retention on the protein precipitate. The assay was linear, the measurement
      precision was 3.3% for MTX and 6.2% for 7OMTX and the clean-up reproducibility
      was 4% for MTX and 3.6% for 7OMTX. By reference to automated fluorescence
      polarization immunoassay, the HPLC method resulted in plasma MTX values 10%
      lower, probably owing to the higher specificity of HPLC. Unsystematically
      sequenced plasma samples from 35 children following 24-h MTX infusions provided
      estimated half-decay times of 16 and 19 h for MTX and 7OMTX, respectively, and
      7OMTX:MTX concentration ratios of 7 at 48 h and of 5 at 72 h from starting
      infusions.

PMID- 8749258
TI  - Simultaneous determination of a new anticancer agent (NB-506) and its active
      metabolite in human plasma and urine by high-performance liquid chromatography
      with ultraviolet detection.
AB  - A high-performance liquid chromatographic method with ultraviolet detection has
      been developed to quantify NB-506 and its active metabolite in human plasma and
      urine. This method is based on solid-phase extraction, thereby allowing the
      simultaneous measurement of the drug and metabolite with the limit of
      quantification of 0.01 microgram/ml in plasma and 0.1 microgram/ml in urine.
      Standard curves for the compounds were linear in the concentration ranges
      investigated. The range for the drug in plasma was 0.01-2.5 micrograms/ml, and
      for the metabolite 0.01-1 microgram/ml. In urine, the range for both compounds
      was 0.1-10 micrograms/ml. The method was validated and applied to the assay of
      plasma and urinary samples from phase I studies.

PMID- 8749259
TI  - Determination of moxidectin in plasma by high-performance liquid chromatography
      with automated solid-phase extraction and fluorescence detection.
AB  - Moxidectin is a newly developed potent anthelmintic agent with a high potency
      although present at very low concentration in cattle plasma. A method is
      described for the determination of moxidectin in plasma using high-performance
      liquid chromatography with fluorescence detection (excitation and emission
      wavelengths 383 and 447 nm, respectively). The fluorescent derivative was
      obtained by a dehydrative reaction with trifluoroacetic anhydride and N
      methylimidazole. The method employs 1-ml plasma samples and has linear
      calibration graphs (r = 0.997) over the concentration range studied, i.e., 0.1-10
      ng/ml. Solid-phase extraction using the Benchmate procedure was used for sample
      preparation. Recoveries at low concentrations (0.1-10 ng/ml) were higher than
      75%. The limit of quantification was 0.1 ng/ml (C.V. 6.95%). The method is
      suitable for the pharmacokinetic study of moxidectin after subcutaneous
      administration to cows.

PMID- 8749260
TI  - Determination of leucogentian violet and gentian violet in catfish tissue by high
      performance liquid chromatography with visible detection.
AB  - A sensitive analytical procedure for the determination of residues of
      leucogentian violet (LGV) and gentian violet (GV) in catfish tissue is presented.
      Frozen (-20 degrees C) catfish fillets were cut into chunks and then blended in a
      Waring blender. A 10-g amount of catfish muscle tissue was homogenized and
      extracted with acetonitrile-buffer, partitioned against methylene chloride, and
      cleaned up on tandem neutral alumina and propylsulfonic acid cation-exchange
      solid-phase extraction cartridges. Samples of 100 microliters (0.5 g equiv.) were
      chromatographed isocratically in 15 min using an acetonitrile-buffer mobile phase
      on a cyano phase column in-line with a post-column PbO2 oxidation reactor. The
      PbO2 post-column reactor efficiently oxidized the LGV to the chromatic GV
      permitting visible detection at 588 nm for both LGV and GV. Linearity was
      demonstrated with standards over the range 0.5-50 ng per injection. Recoveries of
      LGV and GV from catfish tissues fortified at 20, 10, and 1 ng/g were 83.1 +/-
      1.2, 78.4 +/- 4.0, 84 +/- 8 and 92.7 +/- 1.8, 95.0 +/- 2.2, 93 +/- 2 (mean +/-
      S.D., n = 4), respectively.

PMID- 8749261
TI  - Rapid radioassay for metabolites of adenosine and deoxyadenosine in erythrocytes.
AB  - A radioassay has been developed to quantify the uptake and initial metabolism of
      adenosine (Ado) or deoxyadenosine (dAdo) by human erythrocytes. Cell suspension
      and [3H]Ado are mixed at 3-s intervals with a novel dual-syringe apparatus, and
      uptake and metabolism of Ado is stopped by centrifuging the cells through a
      dibutylphthalate layer into perchloric acid. The neutralized cell extract is
      analyzed by two-dimensional chromatography on poly(ethyleneimine)-cellulose
      plates by two procedures using combinations of solvents optimised for the
      separation of nucleosides and nucleobases, and for nucleotides derived from the
      exogenous [3H]Ado.

PMID- 8749262
TI  - Determination of midazolam and its unconjugated 1-hydroxy metabolite in human
      plasma by high-performance liquid chromatography.
AB  - A selective and sensitive high-performance liquid chromatographic method for the
      analysis of midazolam and its unconjugated 1-hydroxy metabolite in plasma samples
      was developed. The compounds were extracted from plasma by a liquid-liquid
      extraction procedure with diethyl ether. Mean analytical recoveries were 87% and
      86% at a concentration of 300 ng/ml for midazolam and 1-hydroxymidazolam,
      respectively, and the quantification limit was 2 ng/ml for a plasma volume of 1
      ml. The separation of midazolam, 1-hydroxymidazolam and flurazepam (internal
      standard) was achieved on a Spherisorb 5 CN column using methanol-2(r)propanol
      (75:25, v/v) containing 0.015% perchloric acid at a flow-rate of 1.5 ml/min. The
      method is sensitive enough for monitoring midazolam and also the unconjugated
      form of the active metabolite in plasma during pharmacokinetic studies.

PMID- 8749263
TI  - Measurement of a new anticonvulsant, (S)-3-(aminomethyl)-5-methylhexanoic acid,
      in plasma and milk by high-performance liquid chromatography.
AB  - A specific and sensitive isocratic method for the measurement of a new
      anticonvulsant, (S)-3-(aminomethyl)-5-methylhexanoic acid, in rat plasma and milk
      is described. Following deproteinization, the compound and internal standard [1
      (aminomethyl)cycloheptaneacetic acid] were derivatized utilizing 2,4,6
      trinitrobenzene sulfonic acid and extracted with cyclohexane. Analytes were
      resolved on a 5 microns Spherisorb ODSII column (250 mm x 4.6 mm) using a mobile
      phase of 57% acetonitrile in 0.1 M ammonium acetate, pH 4.0. Absorbance was
      monitored at 350 nm. Limit of quantitation was 1.00 microgram/ml for a 100
      microliters aliquot of plasma or milk.

PMID- 8749264
TI  - Determination of proguanil and metabolites in small sample volumes of whole blood
      stored on filter paper by high-performance liquid chromatography.
AB  - A method is reported for the determination of proguanil and its two metabolites
      cycloguanil and 4-chlorophenylbiguanide in whole blood and plasma samples
      obtained by thumbprick and stored dry on filter paper. The sample preparation
      involves liquid extraction from the filter paper and subsequent solid-phase
      extraction using C8 Bond-Elut cartridges. Separation and quantification is by a
      previously reported ion-pairing high-performance liquid chromatographic system
      with ODS Hypersil as stationary phase and an 50:50 acetonitrile-pH 2 phosphate
      buffer mobile phase containing 200 mM sodium dodecylsulphate as ion-pairing
      agent. The analytical characteristics of the method are reported. Representative
      concentrations are shown as a function of time from a human subject after
      ingestion of a single 200-mg dose of proguanil hydrochloride. Typical ranges of
      concentration detected by the proposed method in human subjects were proguanil 12
      900 ng/ml, cycloguanil 16-44 ng/ml and 4-chlorophenylbiguanide 1.5-10 ng/ml in
      whole blood.

PMID- 8749265
TI  - Pathophysiological aspects of the renin-angiotensin-aldosterone system in acute
      myocardial infarction.
AB  - Our understanding of the renin-angiotensin-aldosterone system (RAAS) has advanced
      considerably in recent years. The RAAS plays a central role in the control of
      salt and water balance, and in the regulation of blood pressure and
      cardiovascular homeostasis. The haemodynamic changes in the period after
      myocardial infarction stimulate intense activation of both the circulating and
      the local RAAS. This acts through its end-products, angiotensin II and
      aldosterone, to promote sodium and fluid retention, and to increase cardiac
      contractility and systemic vascular tone. There is increasing evidence that, in
      the long term, this apparently adaptive response may be harmful, and might
      contribute to the development of some of the complications seen after infarction.
      Angiotensin II is capable of inducing coronary as well as systemic
      vasoconstriction, and may therefore prolong the duration of ischaemia. The
      response of the RAAS after infarction can be modified pharmacologically.
      Angiotensin converting enzyme (ACE) inhibitor drugs are already the mainstay of
      treatment in heart failure, and have now been shown to have a crucial role in the
      prevention of ventricular remodelling after myocardial infarction. Although the
      precise mechanism of this benefit is unclear, it provides further incentives to
      develop more effective strategies capable of suppressing neurohumoral activity
      following infarction.

PMID- 8749266
TI  - Clinical background to the use of ACE inhibitor therapy after myocardial
      infarction.
AB  - The rationale for using angiotensin converting enzyme (ACE) inhibitor therapy
      after acute myocardial infarction has been largely founded on observations made
      in experimental situations, and in humans before the routine introduction of
      reperfusion therapies. An important area of ongoing debate therefore continues to
      be the role of ACE inhibition as an early adjunct to attempts to achieve and
      maintain patency of infarct-related coronary arteries. Data from clinical trials
      indicate a substantial survival benefit in patients with impaired ventricular
      function, but provide little support for the routine treatment of the remaining
      majority of patients. An important issue in determining whether these agents
      should be used in a more general and long-term secondary prevention role, is
      their potential ability to prevent subsequent reinfarction. However, such a
      strategy is unlikely to be enhanced by either immediate initiation of treatment
      or withdrawal after just 1 month of therapy.

PMID- 8749267
TI  - Prevention of congestive heart failure by ACE inhibition in patients with acute
      myocardial infarction.
AB  - Ischaemic heart disease is a major cause of chronic heart failure in Western
      societies. Despite some progress in the treatment of heart failure, it is still a
      disabling disorder with both high mortality and high morbidity. The incidence of
      chronic heart failure has increased over the past decade, probably as a result of
      the recent success in the management of patients with acute myocardial
      infarction. The importance of measures with potential capacity to prevent the
      development of symptomatic heart failure may be best illustrated by the fact
      that, among patients with left ventricular dysfunction, the prognosis is much
      worse in those with symptomatic failure than in those who are asymptomatic.
      Recently, the efficacy of angiotensin converting enzyme (ACE) inhibitors after
      myocardial infarction has been studied in a number of large placebo-controlled
      trials. These studies indicate that patients with symptomatic or asymptomatic
      left ventricular dysfunction after an acute myocardial infarction should receive
      long-term treatment with an ACE inhibitor and that such treatment may improve
      survival, reduce the incidence of overt heart failure and reduce the risk of
      reinfarction.

PMID- 8749268
TI  - Drug differences between ACE inhibitors in experimental settings and clinical
      practice.
AB  - In recent years, growing evidence has suggested a beneficial effect from the use
      of angiotensin converting enzyme (ACE) inhibitors after myocardial infarction.
      Since important differences between the structure and effects of the various ACE
      inhibitors exist, differences in outcome can be expected. This review discusses
      the structural, pharmacodynamic and pharmacokinetic differences between ACE
      inhibitors administered after myocardial infarction, both in experimental
      settings and in clinical practice.

PMID- 8749269
TI  - Effects of ACE inhibitors on mortality when started in the early phase of
      myocardial infarction: evidence from the larger randomized controlled trials.
AB  - This review summarizes the evidence from five of the larger randomized controlled
      trials evaluating the effects of angiotensin converting enzyme inhibitors started
      in the early phase of myocardial infarction on subsequent mortality and major
      morbidity. Altogether, information on about 98,000 patients is available from
      these trials. In four studies, trial treatment was started within 24 h, and in
      one study within 36 h, of the onset of symptoms of acute myocardial infarction,
      and mortality was assessed after a few weeks or months of treatment. When taken
      together, these trials show that angiotensin converting enzyme inhibitors produce
      a significant 7% relative risk reduction in mortality (P < 0.006), which
      corresponds to an absolute difference of about five fewer deaths per 1,000
      patients treated. The benefits may be greater in higher-risk patients (e.g. those
      with previous myocardial infarction, heart failure or large infarcts). These
      results demonstrate that for a wide range of patients without clear
      contraindications, angiotensin converting enzyme inhibitors started early in
      acute myocardial infarction prevent further deaths in the first few weeks when
      added to standard therapy (aspirin, thrombolytic therapy and beta-blockers). The
      early benefits seen with ACE inhibitors seems to persist for at least the first
      year. The clinical implications of these results are discussed.

PMID- 8749270
TI  - Practical issues for the use of ACE inhibitors in acute myocardial infarction.
AB  - Numerous large, double-blind, randomized trials have demonstrated that, overall,
      angiotensin converting enzyme (ACE) inhibition improves survival of patients
      after acute myocardial infarction (AMI). However, several practical issues
      concerning ACE inhibition in the presence of AMI have not yet been answered.
      These include whether ACE inhibition should be initiated in all patients with
      AMI, how soon ACE inhibition should be attempted in relation to onset of pain and
      possibly thrombolysis, and, lastly, how long ACE inhibition should be maintained
      after the acute event. Each of these issues is addressed, and recommendations are
      made on the basis of the results from recent randomized trials in AMI and
      congestive heart failure.

PMID- 8749271
TI  - Haemorheological consequences of chronic cigarette smoking.
AB  - Smoking is a universally accepted major cardiovascular risk factor, but the
      mechanisms by which it promotes ischaemic vascular disease are not fully
      understood. The changes that chronic smoking exerts on the flow properties of
      blood might contribute to an explanation. It is well documented that smoking
      leads to a rise in haematocrit. It also alters the rheological behaviour of red
      blood cells and increases both plasma viscosity and fibrinogen levels. Finally,
      it increases the total white cell count and modifies leukocyte function. Together
      these changes cumulate in a significant deterioration of the flow properties of
      blood, as evidenced by a steep increase in whole blood viscosity. Alterations of
      blood rheology in turn can promote atherothrombogenesis in several ways. It seems
      possible, therefore, that one mechanism by which smoking increases the risk of
      vascular diseases operates through its complex effects on blood rheology.

PMID- 8749272
TI  - Screening for cardiovascular risk: cost-benefit considerations in a comparison of
      total cholesterol measurements and two compound blood lipid indices.
AB  - BACKGROUND: Serum total cholesterol measurements have been shown to differentiate
      between patients with angiographically confirmed coronary artery disease and
      controls less well than compound indices of cardiovascular risk. Details of
      employees (n = 229) nominated by an occupational health service in a non
      manufacturing firm were used as a starting point for calculations to compare the
      costs and benefits of using compound indices of cardiovascular risk with those of
      total cholesterol measurements alone. METHODS: Healthy employees were defined as
      having a low or a high risk of cardiovascular disease according to either total
      cholesterol level or two compound indices of blood lipid components. The compound
      indices were the ratio of total to high-density lipoprotein (HDL) cholesterol
      (the TC: HDLC ratio) and an 'atherogenic index' defined as ([total cholesterol
      HDL cholesterol] x [apolipoprotein B])/([HDL cholesterol] x [apolipoprotein A]).
      If compound indices discriminate better between people at low and high risk, both
      the number of people given unnecessary advice on lifestyle changes or urged to
      take cholesterol-reducing medication and the number of people not treated because
      of their 'normal' cholesterol levels would be reduced. In our calculations, we
      assumed as 'gains' that (1) the disclosure that a total cholesterol test result
      is false-positive is equal to treatment costs, consultation fee and consumption
      foregone (i.e. resources already used on medication, services etc.) (8909 Nkr [US
      $1 = 7 Nkr]), and (2) the disclosure that a test result is false-negative is
      equal to consultation fee plus loss of 2 h wages (288 Nkr). RESULTS: The
      screening of 100,000 men and 100,000 women would incur a cost of 99 and 710 Nkr,
      respectively, per person assumed to benefit from extended screening using two
      different compound indices. Net gain would be 438 and 192 million Nkr,
      respectively, for the two compound indices. However, the lack of prospective data
      on compound indices suggests the need for cautious interpretation. CONCLUSION:
      Although prospective studies are needed to confirm our findings, the changes in
      number of false-positive and false-negative values achievable using different
      indices suggests a need for greater caution when using single lipid measurements
      as predictors of risk. The calculations of this non-prospective study indicated
      an increased benefit-cost ratio in assessing cardiovascular risk by using
      compound indices of cardiovascular risk compared with total cholesterol
      measurements alone.

PMID- 8749273
TI  - Levels of cardiovascular risk factors in Japanese people living in the UK.
AB  - AIM: We set out to compare levels of cardiovascular risk factors (blood pressure,
      body mass and serum lipids) in Japanese people living in the UK with those of
      Japanese people living in Japan and also with residents of the UK. METHODS: Blood
      samples were taken from individuals attending routine health screening at three
      centres. The study group comprised 879 men and 723 women born in Japan but living
      in the UK; 21 248 Japanese men and 8282 Japanese women living in Japan; and 46
      623 Caucasian men and 4914 Caucasian women living in the UK. RESULTS: In both men
      and women we found significantly higher mean blood pressures and cholesterol
      levels and lower mean triglyceride levels in the expatriate Japanese compared
      with those still living in Japan. These differences were independent of exercise,
      smoking and drinking habits and were not related to self-reported levels of
      stress. They were present even in those Japanese who had been living in the UK
      for less than 1 year. Higher cholesterol levels were associated with consumption
      of a Western diet in women but not in men, whereas mean triglyceride levels were
      lower in men, but not women, eating Western food. CONCLUSION: Our findings
      suggest that the levels of risk factors such as blood pressure and serum lipids
      are for the most part culturally, rather than genetically, determined.

PMID- 8749274
TI  - Diagnostic value of immune cholesterol as a marker for atherosclerosis.
AB  - BACKGROUND: The serum of patients with coronary atherosclerosis contains
      circulating immune complexes including low-density lipoproteins (LDLs). We have
      developed a technique for the evaluation of LDL content in circulating immune
      complexes by measuring total cholesterol levels in polyethylene glycol
      precipitates (immune cholesterol). In the present study, the value of immune
      cholesterol in the diagnosis of atherosclerosis was compared with that of other
      laboratory parameters, such as total cholesterol levels, triglycerides, LDL
      cholesterol, high-density lipoprotein cholesterol, lipoprotein(a), and
      apolipoproteins B and A-1. METHODS: Immune cholesterol and the other parameters
      were determined in blood samples from 200 patients with documented coronary and
      extracoronary atherosclerosis. Coronary atherosclerosis was assessed by coronary
      angiography; stenoses in the aortic arch and branches and in lower-limb arteries
      were evaluated by angiography and ultrasonography. RESULTS: Only immune
      cholesterol and the ratio of apolipoprotein B to apolipoprotein A-1 correlated
      significantly with the severity of coronary atherosclerosis. The accuracy of the
      diagnosis of coronary atherosclerosis by immune cholesterol was 78%, considerably
      higher than that of other laboratory parameters. Use of a combined parameter
      consisting of immune cholesterol, LDL cholesterol, and the patient's age
      increased the diagnostic accuracy to 81%. A high level of immune cholesterol is
      characteristic not only of coronary atherosclerosis but also of extracoronary
      atherosclerosis. The sensitivity, specificity and accuracy of the diagnosis of
      extracoronary atherosclerosis were even higher than those for coronary
      atherosclerosis. CONCLUSION: Immune cholesterol may be employed as a novel marker
      in the diagnosis of advanced atherosclerosis.

PMID- 8749276
TI  - Bibliography of the current world literature.

PMID- 8749275
TI  - Phenol lumbar sympathetic block in diabetic lower limb ischemia.
AB  - BACKGROUND: Patients with arteriosclerotic peripheral vascular disease and lower
      limb ischemia have painful ulceration or incipient gangrene of the lower limb
      with intractable rest pain. The arteriosclerotic changes may preclude any surgery
      other than amputation. METHODS: We examined whether chemical sympathectomy could
      relieve pain, arrest gangrene and postpone amputation, even in diabetic patients.
      RESULTS: Phenol lumbar sympathectomy was performed on 373 patients, of whom 226
      (60.6%) were diabetic. Over 24-120 months of follow-up, 219 patients (58.7%)
      experienced total relief from pain and healing of gangrenous ulcers, although the
      treatment was unsuccessful in 154 patients. A favorable result was marked in
      diabetic patients who had rest pain and in non-diabetic patients who had digital
      gangrene or digital ulcers. Age and sex did not affect the results but heavy
      smoking did. CONCLUSION: Phenol sympathectomy should be considered as an
      alternative to surgical sympathectomy. Furthermore, the technique may be a
      precursor to and even an alternative to amputation in patients who have diabetes
      and advanced arteriosclerosis of the lower limb.

PMID- 8749277
TI  - Estimating the costs of occupational injury in the United States.
AB  - This article estimates workplace injury costs in the U.S. These costs have been
      studied in less detail than most injury costs. Our methods, which mostly use
      regularly published data, produce order-of-magnitude estimates. Overall,
      workplace injuries cost the U.S. an estimated $140 billion annually. This
      estimate includes $17 billion in medical and emergency services, $60 billion in
      lost productivity, $5 billion in insurance costs, and $62 billion in lost quality
      of life. One sixth of the societal costs result from the 3% of workplace injuries
      in motor vehicle crashes. Motor vehicle costs per injury are almost 6 times the
      workplace injury average.

PMID- 8749278
TI  - Head injuries in lateral impact collisions.
AB  - Individual non-minor injuries (Abbreviated Injury Scale (AIS) > or = 2) to the
      head that occurred to belted and unbelted drivers and front seat passengers on
      the stuck side of impacted vehicles were examined. Injury type, injury
      combination, collision severity in relation to type of injury as well as contact
      sources were assessed. Forty-eight percent of injuries were moderate in severity
      (AIS 2). The most common type of injury was the diffuse brain injury, typically
      marked by a short period of unconsciousness, which occurred in collisions of
      lower severity than focal brain and skull fracture injuries. One-hundred and five
      out of 216 (48.6%) of contact sources for all injury types originated from
      outside the vehicle and such exterior sources were more likely to result in high
      severity injuries. Thirty percent of injuries resulted from head contacts with
      other vehicles. The most frequent vehicle interior contact source was the side
      window glass. Diffuse injuries tended to occur independently of other injury
      types and were more likely to originate from an interior rather than exterior
      contact. Preventative measures for head injury reduction in lateral collisions
      are discussed. Overall, the data show that proposed and present European and U.S.
      lateral impact test methods do not address many head injury problems such as
      those included in this study.

PMID- 8749279
TI  - On the prevention of accidents and injuries. A comparative analysis of conceptual
      frameworks.
AB  - The meaning of prevention has changed as new applications of the concept have
      appeared. Ideas presented in eleven different conceptual frameworks are compared.
      Identification of the frameworks took place through searches in databases and
      relevant literature. Five are general by nature, while six relate to injuries and
      accidents. All are supported by just a few parameters, the time dimension being
      the most prominent. Compatibility was established on three additional dimensions:
      level (individual, organizational or societal); direction ("bottom-up" or "top
      down"); and in relation to the trichotomy "host-agent-environment". An attempt to
      synthesize all these dimensions into one general model of accident and injury
      prevention is presented.

PMID- 8749280
TI  - Characteristics of crashes attributed to the driver having fallen asleep.
AB  - While it has been known for some time that crashes can result from the driver
      falling asleep at the wheel, this issue has received less attention in traffic
      safety programs than the role of alcohol or speed of the vehicle. The present
      study was done to investigate the characteristics of crashes attributed to the
      driver being asleep. The study utilized the database at the Highway Safety
      Research Center at the University of North Carolina that is based on the uniform
      crash reporting system in that state. Over the years 1990-1992, inclusive, there
      were 4333 crashes in which the driver was judged to be asleep but not
      intoxicated. The crashes were primarily of the drive-off-the-road type (78% of
      the total) and took place at higher speeds (62% in excess of 50 mph). The
      fatality rate was of similar magnitude to that in alcohol-related crashes with
      fatalities in 1.4% of such crashes (alcohol crashes had fatalities in 2.1%). The
      crashes occurred primarily at two times of day--during the nighttime period of
      increased sleepiness (midnight to 7.00 a.m.) and during the mid-afternoon
      "siesta" time of increased sleepiness (3.00 p.m.). These crashes occurred
      predominately in young people. Fifty-five percent of these were in individuals 25
      years of age or younger, with a peak age of occurrence at age 20 years.
      Sleepiness may play a role in crashes other than those attributed by the police
      to the driver being asleep. Determining the magnitude of this role is a challenge
      to the traffic safety community.

PMID- 8749281
TI  - How drivers sit in cars.
AB  - This paper presents results from a study to measure the separation of the
      driver's head and shoulder to various internal features of the car. Drivers were
      filmed whilst driving in general traffic flow, hence were unaware that they were
      involved in a study. The results show that certain sub-groups of the driver
      population are likely to be more at risk for certain impact types. Small females
      are considerably closer to the steering wheel than the rest of the population,
      and therefore prone to head strikes in frontal impacts. Large males are likely to
      interact with the cant rail and B-pillar in side impacts.

PMID- 8749282
TI  - Daily fluctuations in honolulu motor vehicle accidents.
AB  - Changes in daily motor vehicle accidents during 1990 are examined for the City
      and County of Honolulu. Adjusting for changed reporting criteria, daily accidents
      fluctuate according to an interaction between traffic volume, weekday travel
      patterns, holidays and weather. Fridays, particularly, and Saturdays have more
      daily accidents. Minor holidays generate more daily accidents, but major holidays
      generate fewer daily accidents, primarily because of lower traffic volume.
      Rainfall increases the risk of accidents substantially. The interaction between
      afternoons and rainfall is particularly dangerous. Unemployment also appears to
      reduce daily accidents.

PMID- 8749283
TI  - Young female drivers in New Zealand.
AB  - While a considerable amount is known about young male drivers both in New Zealand
      and overseas, research attention concerning female drivers of any age including
      those under the age of 25 has been far less prevalent. The present paper explores
      the reasons behind the historically low research interest in this population of
      road users, and seeks to provide information on the current status of young
      female drivers in New Zealand, with regard to both travel patterns and crash
      involvement statistics. The findings of the present study suggest that the
      exposure to risk of this group has increased with greater licensing and
      kilometreage. Increased crash involvement was identified for this group, a
      finding accentuated by the fact that this has occurred concurrent with a decrease
      in crash involvement of young male drivers. Drink driving patterns of this group
      are discussed, in response to the finding that the crash involvement and number
      of drink-drive convictions of females 15-24 have increased over time.
      Implications for research and countermeasures are outlined.

PMID- 8749284
TI  - Appropriate frontal barrier tests for belted occupants.
AB  - Vehicle damage from frontal impacts was classified and investigated together with
      injuries sustained by belted front seat occupants. The sample consisted of 1872
      frontal crashes from the Midlands of England. Analysis focused on impacts with
      broad objects that might conceivably be simulated by a barrier test. Two
      asymmetrical front-end damage patterns were commonly identified, and these gave
      the greatest rates of non-minor (Abbreviated Injury Scale (AIS) > or = 2)
      injuries in a range of Estimated Test Speeds from 35 to 52km/h which is the
      regime of current legislative crash tests. The most injurious type involved
      oblique damage caused by a substantial overlap of the struck object. The other
      type was from a small overlap. Objects struck and passenger compartment
      intrusions were compared. Appropriate asymmetrical and deformable barrier
      concepts were discussed. Other findings were connected with the future role of
      full face barriers as used in current tests such as Federal Motor Vehicle Safety
      Standard 208. Fuller overlaps (> 50%) tended to give more torso injuries rated >
      or = AIS 2 caused by seat belt loads and, at high speeds (53-79km/h), caused the
      most fatalities. Full overlaps (100%) rarely resulted in symmetrical intrusion
      into the passenger compartment.

PMID- 8749285
TI  - Treated injuries in northern Vermont.
AB  - OBJECTIVES: To study characteristics of injury events and injuries requiring
      treatment in a Vermont population. METHOD: A one year 30% prospective sample was
      studied of persons from 22 communities who received first physician care for
      injury at the Medical Center Hospital of Vermont. RESULTS: Modal injuries were
      superficial involving skin only among children below age 10, overexertion
      injuries among 10-59 year olds, and fractures among older persons. Among
      interviewed males ages 20-59, 31% of injuries were work related. Among females
      26% were work related. Examining hospitalized cases only would have
      overemphasized falls, chemical injuries, leg fractures, transportation and
      nursing home injuries, and undercounted overexertion injuries, especially to the
      back, arm fractures, and injuries during recreation, work and home activities.
      Most common products/materials in use when injured were recreational equipment
      (24%) and motor vehicles (9%). Those most often causing injury were ground (20%)
      and home structures/construction materials (17%). No product was involved in 39%
      of injury event initiation and 15% of injury causation. CONCLUSION: In order to
      adequately reflect the distribution of treated injuries in the community by
      anatomical area, age, and event type studies must examine both emergency
      department and hospitalized cases and use a data collection system capable of
      recording several parameters to describe injury events and products/materials
      involved.

PMID- 8749286
TI  - Thermal trauma resulting from motor vehicle operation or maintenance.
AB  - Burn injury may result from the operation or maintenance of motor vehicles. We
      reviewed the experience of one burn center with injuries related to motor vehicle
      use over the 6 year period 1987-1992. One hundred and fifty patients with motor
      vehicle related burns were identified comprising 11.3% of all admissions for this
      period. The mean extent of burn injury was 22.8% total body surface area with a
      mean full thickness (third degree) burn size of 11.7%. The average hospital
      length of stay was 42.41 days. The most common mechanisms of injury were
      collisions resulting in fire (n = 48), carburetor priming (n = 37) and scalding
      from radiator fluid contact (n = 27). Burns resulting from vehicle operation or
      maintenance are costly and potentially preventable.

PMID- 8749287
TI  - The effects of seat belts on injury severity of front and rear seat occupants in
      the same frontal crash.
AB  - Data on passenger cars in frontal crashes were reviewed using NASS 1980-1991.
      Only crashes with one or more rear seat passengers were included. Combinations
      (pairs) were made based on restraint use: lap-shoulder belts in the front seat
      (or no belts worn) and lap belts, (or belts worn) in the rear seat. Passive belts
      or child restrained occupants were not included. The AIS was used for injury
      severity. The data indicate the rear seat to be a safer environment. Lap belted
      rear seat occupants always fared better than their front seat counterparts.

PMID- 8749288
TI  - A case-control study of child bicycle injuries: relationship of risk to exposure.
AB  - In order to assess the relationship of the risk of injury requiring hospital
      attendance in children riding bicycles to sociodemographic factors and to
      measures of exposure, a population-based case-control study is being undertaken
      in a large area of suburban Melbourne, Australia. Particular attention is given
      to the measurement of individual exposure in several dimensions. Analysis of
      interim data from 109 cases and 118 controls shows that 51% of injuries occurred
      while the child was playing rather than making a trip on the bicycle and only 22%
      involved another vehicle. Boys used bicycles more commonly than girls but there
      was minimal evidence of an increased risk of injury in boys, adjusting for
      exposure. There was no evidence for an age trend in injury risk, but children
      from families in the lowest income category were at significantly increased risk.
      Exposure measures showed complex patterns of association with injury risk.
      Estimated time spent riding was more closely associated with risk than distance
      travelled, with an odds ratio of 2.2 (95% confidence interval 1.1-4.2) for
      children riding for more than 3 hours per week compared to children riding less
      than 1 hour. Riding more than 5 km on the sidewalk was also associated with
      increased risk (odds ratio 3.1, 95% CI 1.1-8.5). The elevated risk associated
      with sidewalk riding may be due to difficulties in negotiating uneven surfaces.
      The case-control study provides an ideal design for this type of investigation
      but valid and reliable measurement of exposure is difficult.

PMID- 8749289
TI  - Analysis of fatal motorcycle crashes: crash typing.
AB  - There were 2074 crashes fatal to a motorcycle driver in the United States during
      1992. A computer program was developed to convert Fatal Accident Reporting System
      (FARS) data for these crashes into standard format English language "crash
      reports". The computer generated reports were analyzed and crash type categories
      were defined. Five defined crash type categories accounted for 1785 (86%) of the
      2074 crash events: Ran off-road (41%); ran traffic control (18%); oncoming or
      head-on (11%); left-turn oncoming (8%); and motorcyclist down (7%). Alcohol and
      excessive speed were common factors associated with motorcyclist crash
      involvement. Left turns and failure to yield were common factors associated with
      the involvement of other motorists. Suggested countermeasures include helmet use
      and enforcement of speed and impaired driving laws.

PMID- 8749290
TI  - Driver licenses as a measure of older drivers' exposure: a methodological note.
AB  - The limitations of the number of driver licenses as an estimate of driving
      exposure were demonstrated by comparing Finnish and Swedish driver licensing
      practices, licensing rates and accident rates of older drivers. In Sweden, there
      is no screening for older license holders, and most of them keep their licenses
      for life. In Finland, there is a heavy and costly medico-legal control system for
      older license holders, leading to both screening and self-screening.
      Consequently, in the two countries, the numbers of driver licenses do not reflect
      the numbers of active older drivers in the same manner. This difference affects
      the comparative accident statistics: with respect to population, Finland and
      Sweden have similar age trends in accidents risk, but with respect to the number
      of driver licenses, the Finnish older drivers seem to have a higher risk of
      accident than the Swedish ones. It is concluded that if group comparisons of
      accident risk are presented using the number of driver licenses as an estimate of
      exposure, the licensing legislation and practice should affect all the groups in
      an identical manner for the comparison to be valid.

PMID- 8749291
TI  - The funding of graduate medical education.

PMID- 8749292
TI  - Survivorship analysis of acetabular revision in medial, lateral, and global
      primary osteoarthritis.
AB  - Acetabular revision rates after cemented total hip arthroplasty vary from series
      to series in the literature. Little attention has been paid to the type of
      primary osteoarthritis in these previous series. We studied 782 cemented total
      hips in 671 patients with an average follow up of 7.5 years. Acetabular revision
      rates were analyzed in medial, lateral, and global primary osteoarthritis using
      survivorship analysis. Medial osteoarthritis was associated with a higher
      acetabular revision rate when compared to lateral osteoarthritis (P = .015). No
      differences were noted in acetabular revision rates when the preoperative
      diagnosis was medial vs global or lateral vs global primary osteoarthritis (P =
      .18 and P = .45, respectively). According to this study, a preoperative diagnosis
      of medial primary osteoarthritis should be added to a list of several factors
      associated with increased cemented acetabular failure, especially in the Charnley
      prosthesis.

PMID- 8749293
TI  - The role of a composite, demineralized bone matrix and bone marrow in the
      treatment of osseous defects.
AB  - The efficacy of demineralized bone matrix (DBM) used alone and with bone marrow
      as a graft material in the treatment of osseous defects was evaluated in 48
      patients. Of these 48 patients, 39 were available to follow up and review. Follow
      up averaged 19 months for all patients. In the entire series, 30 of 39 patients
      demonstrated osseous union for a 77% success rate. Patients with fracture
      nonunion represented the most recalcitrant group clinically, with union achieved
      in only 61% of these cases. Overall, the 39 patients grafted with DBM
      demonstrated healing that was comparable to results achieved with standard iliac
      crest bone graft. The results indicate the DBM and marrow composite grafting is a
      suitable alternative to autologous iliac crest bone graft for use in certain
      clinical situations, such as bone defects in children, comminuted fractures with
      associated bone loss, nonunited fractures, or to augment an intended arthrodesis
      site.

PMID- 8749294
TI  - Splint immobilization of gamekeeper's thumb.
AB  - Thirty-nine patients diagnosed with 40 acute complete ruptures of the ulnar
      collateral ligament of the thumb metacarpophalangeal joint were treated primarily
      with thumb spica splint immobilization. Duration of splinting ranged from 8 to 12
      weeks. Thirty-four of these injuries (85%) followed for 1 to 5 years (average 2.4
      years) healed without significant instability, arthrosis, pain, or stiffness
      (range of motion within 80% of the contralateral hand). Six ruptures (15%)
      demonstrated persistent instability and pain at 12 weeks and were treated with
      surgical reconstruction. Currently accepted guidelines for surgical intervention
      as primary treatment for ligamentous disruption at the thumb metacarpophalangeal
      joint may need revision. This study suggests that splint immobilization is an
      effective primary treatment modality. The minority of patients who demonstrate
      persistent laxity can be successfully treated surgically with excellent results.

PMID- 8749295
TI  - Results of CFV total wrist arthroplasty: review and early report.
AB  - Articulated total wrist arthroplasties have been used in the United States since
      1974. In the 1980s the CFV wrist was developed in an attempt to reduce the
      incidence of imbalance, loosening, and bone resorption that has been seen in the
      early implants, and also to eliminate the use of bone cement. Since 1988, we have
      implanted 15 of these wrists. To date, nine patients are satisfied because of
      pain relief and motion; however, there have been 6 failures: 2 for infection, 3
      because of a loose distal component, and 1 because of balance. Other problems
      that have been observed are flexor tenosynovitis, carpal tunnel syndrome, and a
      balancing problem.

PMID- 8749296
TI  - Traumatic inferior hip dislocation in an adult (luxatio erecta).

PMID- 8749297
TI  - Total knee replacement with patella magna and pagetoid patella.

PMID- 8749298
TI  - Core decompression as a novel treatment for early Freiberg's infraction of the
      second metatarsal head.

PMID- 8749299
TI  - Osteochondritis dissecans: imaging modalities.

PMID- 8749300
TI  - Sliding and ATPase.
AB  - Sliding machines composed of F-actin and myosin or microtubules and kinesin or
      dynein convert the free energy of ATP hydrolysis into sliding movements and
      mechanical work. Development of optical microscopy with micromanipulation
      techniques has made possible direct observation of single events of sliding
      exhibited by single sliding machines. The experimental data and theoretical
      consideration suggest that the influx-efflux coupling in these machines may be
      loose. Specific characters of sliding machines are summarized and the problems we
      have for understanding of the coupling mechanism are discussed.

PMID- 8749301
TI  - Crystallization of mouse lung carbonyl reductase complexed with NADPH and
      analysis of symmetry of its tetrameric molecule.
AB  - Mouse lung carbonyl reductase (MLCR), which belongs to the short-chain
      dehydrogenase/reductase family, is an oxidoreductase involved in the metabolism
      of biogenic and xenobiotic carbonyl compounds. The crystals of MLCR complexed
      with its cofactor NADPH belong to a monoclinic space group P2(1) with dimensions
      a = 79.73 A, b = 105.5 A, c = 60.87 A, and beta = 91.43 degrees. X-ray
      diffraction data were collected up to 1.8 A resolution using a macromolecule
      oriented Weissenberg camera at the Photon Factory synchrotron radiation source.
      Studies using a self-rotation function revealed the presence of a twofold
      rotational symmetry relating the subunits. This suggests that the tetrameric MLCR
      molecule has the 222 point group symmetry.

PMID- 8749302
TI  - Transcriptional activation of the melanocyte-specific genes by the human homolog
      of the mouse Microphthalmia protein.
AB  - Mi protein encoded at the mouse microphthalmia (mi) locus is a transcription
      factor with a basic helix-loop-helix/leucine zipper structure. To assess the
      function of the human homolog of Mi protein, termed microphthalmia-associated
      transcription factor (MITF), we analyzed the effects of MITF on the promoter
      function of the mouse tyrosinase and tyrosinase-related protein 1 (TRP-1) genes.
      These two gene promoters are able to direct transcription preferentially in
      melanin-producing cells, and an enhancer element M box of 11 bp, containing a
      CATGTG motif, is conserved in both promoters. By transient expression assays, we
      have localized the cis-acting element of the tyrosinase gene responsible for
      pigment cell-specific expression to the proximal 82-bp region, which contains a
      CATGTG motif (positions -12 to -7) but lacks the M box (positions -107 to -97).
      We also provide evidence that the 82-bp region and the M box are involved in the
      transactivation of the tyrosinase promoter by MITF and that the M box is bound by
      MITF in vitro. Furthermore, MITF activated the TRP-1 gene promoter possibly
      through the M box (positions -44 to -34). These results suggest that MITF is a
      common factor regulating transcription of the pigment cell-specific genes.

PMID- 8749303
TI  - Crystal structure of Streptomyces erythraeus trypsin at 1.9 A resolution.
AB  - A trypsin-like serine protease from Streptomyces erythraeus (abbreviated as SET)
      has been crystallized at pH 7, which is within its active pH range. The crystal
      structure of SET has been solved by molecular replacement using the atomic model
      of Streptomyces griseus trypsin (SGT), which is 37% homologous with SET, and
      refined to the crystallographic R factor of 0.199 for 15,878 reflections with
      Fo/sigma(F) > 3 between 7 and 1.9 A resolution. The final model of SET contains
      1,619 protein atoms and 97 water molecules. No Ca2+ ion is present in SET
      apparently because (i) the two carboxylate groups from two Glu residues, which
      bind a Ca2+ ion in bovine trypsin (BT) or SGT, have disappeared; and (ii) a
      guanidino group from an Arg residue is unfavorably present in the potential
      binding region. There is an unusual type II beta-turn in which the third residue
      is Asp instead of Gly. This Asp residue is the only non-Gly residue significantly
      outside the allowed regions in the Ramachandran map. The three-dimensional
      structure of SET is essentially the same as those of other trypsins of mammalian
      origin. The 211 C alpha atoms of SET exhibit an r.m.s. deviation of 1.16 A with
      equivalent atoms of BT, and the 208 equivalent C alpha atoms between SET and SGT
      exhibit an r.m.s. deviation of 1.09 A. The large deviations in C alpha positions
      between SET and BT or between SET and SGT are mainly observed in the first
      domain. The conformations of the side-chains of the catalytic triad are mutually
      similar to each other in these three proteases. Each of the chi 1 torsion angles
      of the three residues is distributed within +/- 5 degrees from each corresponding
      mean value. The hydrogen bond distances related to the side-chains in the triad
      coincide fairly well, though the relative disposition of the side-chains differs
      by 0.1-0.6 A among SET, BT, and SGT. The hydrogen bond network concerned with
      Ser(195), Asp(189), and water molecules in the substrate binding pocket differs
      from that in BT or SGT.

PMID- 8749304
TI  - Instrumentation and applications of an automated C-terminal fragment peptide
      fractionator for C-terminal sequence analysis of proteins.
AB  - A novel automated C-terminal fragment peptide fractionator has been constructed.
      Digests with lysyl endopeptidase were covalently immobilized on p-phenylene
      diisothiocyanate polymer beads. Only the C-terminal fragment, which contains no
      lysyl residue, was liberated by cleavage at the first peptide bond of the
      immobilized fragment peptides with trifluoroacetic acid, and it was automatically
      collected. The whole procedure was automatically and precisely performed under
      microprocessor control in a nitrogen atmosphere. The resulting fragment was
      sequenced without further purification. Sequences of both N- and C-terminal
      regions can be routinely obtained for ca. 100 pmol samples by the use of a
      conventional automated Edman-type protein sequencer.

PMID- 8749305
TI  - Substrate activating mechanism of short-chain acyl-CoA, medium-chain acyl-CoA,
      long-chain acyl-CoA, and isovaleryl-CoA dehydrogenases from bovine liver: a
      resonance Raman study on the 3-ketoacyl-CoA complexes.
AB  - We have shown previously that acetoacetyl-CoA bound to medium-chain acyl-CoA
      dehydrogenase from pig kidney is transformed into an enolate form, O = C(3)-C(2)H
      = C(1)-O-, and that the interaction between the C(4a) = N(5) moiety of flavin and
      the O = C(3)-C(2)H = C(1)-O- moiety of acetoacetyl-CoA is important for the
      charge-transfer interaction [Nishina, Y. et al. (1992) J. Biochem. 111, 699-706].
      In this study, we examined four kinds of acyl-CoA dehydrogenases [short-chain
      acyl-CoA (SCAD), medium-chain acyl-CoA (MCAD), long-chain acyl-CoA (LCAD), and
      isovaleryl-CoA (IVD) dehydrogenases] from bovine liver. The Raman spectra of non
      labeled and isotopically labeled acetoacetyl-CoA in keto-form revealed that the
      1,716-cm-1 and 1,650-cm-1 bands were derived from the C(3) = O and the C(1) = O
      stretching mode, respectively. In the charge-transfer complexes of acetoacetyl
      CoA with the four kinds of dehydrogenases, the resonance Raman (RR) bands
      corresponding to the C(3) = O and the C(1) = O of acetoacetyl-CoA were observed
      at around 1,643-1,622 and 1,506-1,476 cm-1, respectively, indicating that
      acetoacetyl-CoA was transformed into the enolate form as the result of the
      complexation with the enzymes. Further, in RR spectra with excitation at 632.8
      nm, within the charge-transfer band of the complexes of acetoacetyl-CoA with the
      four acyl-CoA dehydrogenases, both bands associated with the C(4a) = N(5) moiety
      of oxidized flavin and the O = C(3)-C(2)H = C(1)-O- moiety of acetoacetyl-CoA
      were enhanced, but the benzene portion of oxidized flavin was not. These results
      indicate that the substrate activating mechanism is common to all four kinds of
      dehydrogenases, i.e., the interaction between the C(1) = O of acetoacetyl-CoA and
      the positively polarized atoms of the enzymes located in close proximity to the
      oxygen atom of C(1) = O is important, and the C(4a) = N(5) moiety of flavin
      participates in the interaction. Some kinds of 3-ketoacyl-CoAs were tested
      instead of acetoacetyl-CoA and essentially similar results were obtained. The
      positions of the bands derived from the C(1)-O- moiety of 3-ketoacyl-CoAs were
      different by ca. 30 cm-1 in two groups, i.e., ca. 1,475 cm-1 for SCAD and MCAD
      and ca. 1,505 cm-1 for LCAD and IVD, that is, RR spectra can classify the four
      dehydrogenases into two groups.

PMID- 8749306
TI  - Chemical modification of histidyl residues in D-amino acid oxidase from
      Rhodotorula gracilis.
AB  - D-Amino acid oxidase was inactivated by DEP at 30 degrees C and pH 7.5. The
      reaction followed pseudo-first-order kinetics with a second-order rate constant
      of 0.254 mM-1.min-1. The pH dependence of the inactivation showed the involvement
      of a group with a pK of 6.6. The presence of substrate or benzoate protected the
      enzyme against inactivation. Difference spectra at 242 nm and the reversal of the
      inactivation in the presence of 1 M hydroxylamine or 0.1 M NaOH pointed to the
      modification of histidine residues. The statistical analysis of the residual
      fractional activity versus the number of modified histidine residues led to the
      conclusion that one histidine residue is essential for the enzyme activity.

PMID- 8749307
TI  - Identification of the reactive histidine of cucumisin, a plant serine protease:
      modification with peptidyl chloromethyl ketone derivative of peptide substrate.
AB  - A radioactive peptidyl chloromethyl ketone derived from substrates of cucumisin,
      3H-labeled Z-Ala-Ala-Pro-Phe-chloromethyl ketone (3H-ZAAPFCK), was synthesized.
      When cucumisin was incubated with a 100-fold molar excess of 3H-ZAAPFCK for 16 h,
      98% of the cucumisin activity was inhibited and about 0.93 mol of 3H-ZAAPFCK was
      incorporated in 1 mol of cucumisin. The 3H-ZAAPFCK-modified cucumisin was reduced
      and pyridylethylated, and then digested by trypsin. The radioactive peptide
      fragment was isolated and its amino acid sequence was determined. The radioactive
      fragment contained 32 amino acid residues and the sequence around the labeled
      residue was found to be -Asp-Thr-Asn-Gly-(His)-Gly-Thr-His-Thr-Ala-. This
      sequence is analogous to that around the reactive site histidine residue of the
      subtilisin family.

PMID- 8749308
TI  - Isolation and characterization of cell-specific cDNA clones from a subtractive
      library of the ocular ciliary body of a single normal human donor: transcription
      and synthesis of plasma proteins.
AB  - A subtractive cDNA library was developed for the purpose of identifying cell
      specific genes expressed within the human ocular ciliary body, a tissue
      responsible for regulating aqueous humor secretion and intraocular pressure.
      Partial DNA sequence of a large number of cDNA clones and homology searches of
      nucleic acid and protein databases revealed significant homologies to at least 90
      independently known genes. A group of biologically significant genes that were
      previously not known to have transcriptional expression in the ciliary body,
      complement component C4; alpha 2 macroglobulin; selenoprotein-P; and
      apolipoprotein D, were further demonstrated by Northern hybridization. Antibodies
      to these and other proteins (i.e., tyrosinase-related protein and pigment
      epithelium-derived factor) confirmed their cell-restricted expression in ciliary
      epithelial cells (pigmented, nonpigmented), or vascular endothelial cells. We
      provide evidence that two human plasma proteins, complement component C4 and
      alpha 2-macroglobulin are metabolically labeled with [35S]methionine in ciliary
      processes explants, suggesting that the ciliary body is an organ of synthesis and
      secretion of plasma proteins present in aqueous humor. These results challenge
      the notion that plasma proteins in aqueous humor are imported from outside of the
      eye. The subtractive cDNA library reported in this work should be very useful for
      identifying potential candidate genes in ocular abnormalities affecting the
      ciliary body, or involved in the regulation of intraocular pressure.

PMID- 8749309
TI  - Deoxyribonuclease I from rat urine: affinity purification, characterization, and
      immunochemical studies.
AB  - Deoxyribonuclease I (DNase I) from rat urine was purified about 3,000-fold to
      apparent homogeneity with a 14% yield by affinity chromatography utilizing
      polyguanylic acid-agarose and DNA-cellulose. The purified enzyme preparation was
      found to contain no other detectable nucleases. Isoelectric focusing
      electrophoresis revealed that all six isoelectric forms of the enzyme had been
      purified, and the resulting bands all contained DNase I activity. Quantitative
      amino acid analysis and N-terminal amino acid sequencing were performed on the
      purified DNase I. The N-terminal sequence up to the 15th residue of the enzyme
      was identical to that of rat parotid DNase I. The enzyme was found to be a
      glycoprotein, containing 1 fucose, 10 galactose, 17 mannose, 12 glucosamine, and
      at least 3 sialic acid residues per molecule. The isoelectric multiplicity of the
      enzyme was partly due to differences in the sialic acid content of the isoforms.
      Gel filtration on Superose 12 and electrophoresis on sodium dodecyl sulfate
      polyacrylamide gels indicated an approximate molecular mass for DNase I of 32
      kDa. The enzyme had an optimum pH of 6.5 and required divalent cations such as
      Ca2+ for its activity. Its activity was inhibited by 1 mM EDTA and EGTA, but not
      G-actin. An antibody against the purified enzyme was found to be monospecific
      against rat urine and the pure antigen, and completely blocked the activity of
      the purified enzyme.

PMID- 8749310
TI  - Exogenous type-II phospholipase A2 stimulates prostaglandin synthesis in rat
      liver-derived BRL-3A cells in the presence of tumor necrosis factor alpha.
AB  - The effect of extracellular type-II phospholipase A2 (PLA2) on prostaglandin (PG)
      synthesis has been studied using rat liver-derived BRL-3A cells. The addition of
      type-II PLA2 to the medium of BRL-3A cells resulted in a marked decrease in the
      enzymatic activity in the medium. An immunochemical study involving an anti-(type
      II PLA2) antibody revealed that a significant amount of PLA2 was attached to the
      surface of type-II PLA2-treated BRL-3A cells. Heparin inhibited the binding of
      PLA2 almost completely. Only modest release of PGE2 over the control value was
      observed when cells were treated with PLA2 alone or tumor necrosis factor alpha
      (TNF alpha) alone, whereas PGE2 production as well as arachidonic acid release
      from phospholipids was augmented more than additively in the presence of both
      type-II PLA2 and TNF alpha. Furthermore, pretreatment of cells with type-II PLA2
      followed by subsequent stimulation by TNF alpha caused an appreciable increase in
      PGE2 production. Thus, type-II PLA2 bound to cell-surface heparin-like molecules
      may exert its activity and participate in eicosanoid generation only in the
      presence of TNF alpha.

PMID- 8749311
TI  - Effect of salt concentration on the pKa of acidic residues in lysozyme.
AB  - We determined the pKa values of acidic residues in hen lysozyme by comparing the
      pH dependency of stability between wild type and mutant lysozymes in which a
      negative charge is eliminated. In the comparison of the stability between wild
      type and a mutant lysozyme, the difference in pH titration curve between them
      could be expressed as a two-state process involving protonation of a single
      acidic residue. The results strongly indicated that the Aune and Tanford theory
      of protein denaturation [Aune, K.C. and Tanford, C. (1969) Biochemistry 8, 4579
      4585] is applicable to protein stability in solution. On the other hand, the pKa
      values of acidic residues in the presence of low (5 mM) or high (400 mM) salt
      concentration were determined by means of two-dimensional NMR. We found that the
      pKa values obtained from the pH dependency of stability were close to those from
      the NMR experiment under the high salt condition. Moreover, by comparing pKa
      values at high salt and low salt concentrations, we could evaluate the dependency
      of two electrostatic interactions (salt bridge and charge-helix dipole
      interaction) on salt concentration.

PMID- 8749312
TI  - Partially deacetylated chitin and hyaluronan induce glycogenolysis in perfused
      rat liver.
AB  - Mannan interacts with mannose/N-acetylglucosamine (GlcNAc) receptors on the
      surface of both Kupffer cells and endothelial cells in the liver, and induces
      glycogenolysis through production of peptide-leukotriene (LT) in the perfused rat
      liver. In the present study, we examined whether positively and negatively
      charged GlcNAc-containing polysaccharides stimulate glycogenolysis in perfused
      rat liver. Infusion of the former, 67% deacetylated chitin (DAC), induced
      biphasic increases in glucose production and a steep decrease in oxygen
      consumption by the liver. ONO-1078, an LT D4 receptor antagonist, abolished the
      suppression of oxygen consumption and reduced the glucose production by DAC.
      Infusion of the latter, hyaluronan, stimulated glucose production with a
      concomitant increase in oxygen consumption. Ibuprofen, a cyclooxygenase
      inhibitor, reduced the glucose production by hyaluronan. Sequential infusions of
      mannan and DAC, but not hyaluronan, did not induce glycogenolytic responses when
      mannan was infused 20 min before the second stimulation. These results suggest
      that DAC, but not hyaluronan, stimulates mannose/GlcNAc receptors in the perfused
      rat liver, and that potent immunological activity induced by DAC may be mediated
      by activation of the receptors.

PMID- 8749313
TI  - Visualization of dystrophic muscle fibers in mdx mouse by vital staining with
      Evans blue: evidence of apoptosis in dystrophin-deficient muscle.
AB  - Degenerating muscle fibers in the skeletal muscle of mdx mice were visualized by
      vital staining with Evans blue. Evans blue injected intravenously stained only
      degenerating muscle fibers which were visible as blue fibers macroscopically and
      could also be seen as red fluorescent fibers microscopically. Evans blue-stained
      muscle fibers were either hypercontracted or degrading. Intact or regenerating
      muscle fibers in mdx mice and muscle fibers in B10 control mice were not stained
      with the dye. DNA isolated from Evans blue-stained fibers exhibited fragmentation
      to approximately 180 base pairs on agarose gel electrophoresis. Such DNA
      fragmentation was not found in DNA from unstained muscle fibers in mdx or B10
      mice. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling
      (TUNEL)-positive myonuclei were also found in Evans blue-stained muscle fibers
      but not in unstained ones. These results indicate that degenerating muscle fibers
      in the mdx mouse show an increase in membrane permeability and undergo apoptosis.
      Vital staining with Evans blue is useful not only for distinguishing degenerating
      muscle fibers, but also for studying the degeneration process biochemically in
      dystrophin-deficient muscle. This method may also be useful for evaluating the
      therapeutic effects of drug administration, gene transfer, and myoblast transfer
      in the mdx mouse.

PMID- 8749314
TI  - Blood coagulation factor IX-binding protein from the venom of Trimeresurus
      flavoviridis: purification and characterization.
AB  - The coagulation factor IX/factor X-binding protein (IX/X-bp) from the venom of
      Trimeresurus flavoviridis is a heterogeneous two-chain protein, and the structure
      of each chain is similar to that of the carbohydrate-recognition domain of C-type
      lectins, such as asialoglycoprotein receptors, pancreatic stone protein, and the
      Fc epsilon receptor for immunoglobulin E. Analysis of the binding properties of
      IX/X-bp revealed that it binds to the gamma-carboxyglutamic acid (Gla)-containing
      domains of factors IX and X [Atoda, H. et al. (1994) Eur. J. Biochem. 224, 703
      708]. In the present study, we isolated another anticoagulant protein that binds
      to factor IX but is not to factor X. This protein, designated IX-bp, inhibited
      factor IXa-induced clotting but not factor Xa-induced clotting, whereas IX/X-bp
      inhibits both. The concentration of IX-bp for half-maximal binding to solid-phase
      bovine factor IX was 0.4 nM whereas IX-bp did not bind to factor X even at 40 nM.
      The binding of IX-bp to solid-phase factor IX was inhibited by the addition of
      Gla-domain peptide of factor IX, indicating that IX-bp binds to the Gla-domain
      region of factor IX. IX-bp had two Ca(2+)-binding sites with different affinities
      for Ca2+ ions. At pH 7.5, the apparent Kd values for these sites were 14 and 130
      microM, respectively. IX-bp was a two-chain protein (27.5-kDa band before
      reduction and 16.8- and 15.7-kDa bands after reduction on SDS-PAGE) and it
      reacted with immunoglobulin G against IX/X-bp. The complete amino acid sequence
      of IX-bp was determined. The 16.8-kDa chain (A chain) of IX-bp consisted of 129
      residues, of which 19 were different from those in the A chain of IX/X-bp (129
      residues). The sequence of the 15.7-kDa chain (B chain) was identical to that of
      the B chain of IX/X-bp (123 residues). We conclude that IX-bp is a protein that
      is structurally similar to but functionally different from IX/X-bp. The
      difference of binding specificity between IX-bp and IX/X-bp presumably arises
      from the sequence differences in the A chains.

PMID- 8749315
TI  - Regions of the molecule responsible for substrate specificity of monoamine
      oxidase A and B: a chimeric enzyme analysis.
AB  - To examine regions of the monoamine oxidase (MAO, EC 1.4.3.4) molecule
      responsible for substrate recognition, a series of these enzymes, in which
      discrete regions in one molecule were substituted by corresponding sequences of
      the other, were constructed from the cDNAs of rat liver MAO A and MAO B and were
      expressed in yeast, Saccharomyces cerevisiae. Substrate specificities of the
      original and chimeric enzymes were examined in terms of the maximum activity
      (Vmax) and the affinity (Km) for serotonin, beta-phenylethylamine (PEA), and
      benzylamine. Chimeric enzymes with the amino-terminal portion (about 220
      residues) and the amino-terminal and middle portions (about 400 residues) of MAO
      A and MAO B, respectively, exhibited substantially the same Km values as those of
      the parent enzymes. Extension of the substitution in the middle portion of a
      chimeric enzyme to the second half of the amino-terminal portion resulted in
      conversion of the Km values for serotonin to those of the counterpart. Data on
      relative Vmax values of the chimeric enzymes for the three substrates revealed
      that the relative catalytic activities were mainly determined by the presence of
      the middle portion. We conclude from these observations that the region between
      about residues 120-220 and about residues 50-400 is responsible for determination
      of the substrate specificity of MAO A and MAO B, respectively, while the middle
      portion, of about residues 220-400, may relate to the relative catalytic activity
      towards substrates.

PMID- 8749316
TI  - Intracellular targeting of lysosomal cathepsin D in COS cells.
AB  - Cathepsin D carries a mannose 6-phosphate sorting signal which is recognized by a
      specific mannose 6-phosphate receptor, presumably at the site of the trans Golgi
      network, which segregates cathepsin D from the secretory proteins, and results in
      targeting of the enzyme to the acidic prelysosomal compartments and lysosomes in
      mammalian cells. Recent evidence implies that another sorting signal resides
      within the polypeptide backbone of the precursor cathepsin D. To evaluate the
      role of the propeptide region of cathepsin D in mannose 6-phosphate receptor
      independent targeting to lysosomes, we prepared a deletion mutant of rat
      cathepsin D lacking the propeptide portion and analyzed its intracellular
      targeting mechanism after transfection of the mutant cDNA as well as the wild
      type cDNA into COS cells. The glycosylated mutant protein was retained
      intracellularly, and extracellular release of mutant protein was not observed
      after a 48 h chase. A cell fractionation experiment demonstrated that in the
      cells expressing the wild-type cathepsin D, the processed form of 44 kDa
      cathepsin D was recovered in the dense lysosomal fraction. In contrast, in the
      cells expressing the mutant protein, virtually all of the cell-associated
      cathepsin D was present in the light fraction which was enriched in the marker
      enzyme NADPH cytochrome c reductase, and this molecular form of cathepsin D was
      not observed in the dense lysosomal fraction. An immunofluorescence study
      revealed that the deletion mutant protein was accumulated within the endoplasmic
      reticulum, unlike the wild-type protein. These results suggest that the mutant
      cathepsin D is not correctly recognized by the intracellular sorting system in
      the endoplasmic reticulum, implying that the propeptide region of cathepsin D is
      essential for the export of cathepsin D from the endoplasmic reticulum.

PMID- 8749317
TI  - NMR investigation of echinomycin binding to d(ACGTTAACGT)2: Hoogsteen versus
      Watson-Crick A.T base pairing between echinomycin binding sites.
AB  - The structure of the echinomycin complex with the self-complementary DNA decamer
      d(ACGTTAACGT)2 has been investigated in solution by proton NMR spectroscopy.
      Echinomycin binds as a bisintercalator at the CpG steps. An analysis of the
      intermolecular NOE patterns defined the position and orientation of the bound
      drug molecule. The terminal A.T base pairs are Hoogsteen base-paired, whereas the
      central four A.T base pairs are clearly Watson-Crick base-paired. Thus, the
      presence of the extra A.T base pairs between the binding sites appears to prevent
      the formation of Hoogsteen base pairs immediately adjacent to the binding site.
      All four central A.T base pairs are destabilized relative to those in the free
      DNA. Because there is no evidence for unwinding of the DNA duplex in the complex
      relative to the free DNA, we conclude that the hypersensitivity to DNA cleavage
      reagents distal to echinomycin binding sites might be due to the destabilization
      of DNA structure induced by the drug binding.

PMID- 8749318
TI  - Fluorescence energy transfer study of troponin C-melittin complex.
AB  - Fluorescence energy transfer study of rabbit skeletal troponin C (TnC), which
      binds a donor, dansylaziridine, to Met-25 in helix A and an acceptor, 5
      (iodoacetamido)eosin, to Cys-98 in helix E revealed (i) the donor-acceptor
      distance did not change upon Mg2+ and Ca2+ binding to TnC, (ii) melittin binding
      to Ca(2+)-free TnC induced a remarkable decrease in the donor-acceptor distance
      both in the presence and absence of Mg2+, and (iii) Ca2+ binding to TnC in TnC
      melittin complex induced a characteristic increase in the donor-acceptor
      distance. These results indicate that TnC assumes a contracted structure upon
      binding of the basic amphipathic TnC-binding peptide, melittin, and that it
      undergoes a characteristic structural change that includes a displacement of
      helix A away from helix E upon Ca2+ binding to TnC in the TnC-melittin complex.

PMID- 8749319
TI  - Inhibitory effect of a synthetic protease inhibitor (gabexate mesilate) on the
      respiratory burst oxidase in human neutrophils.
AB  - We investigated the mechanism by which the synthetic protease inhibitor gabexate
      mesilate inhibits the production of the superoxide anion by human neutrophils. We
      found that gabexate mesilate suppressed SOD-inhibitable cytochrome c reduction in
      a dose-dependent manner in intact neutrophils activated with phorbol ester.
      Gabexate mesilate slightly scavenged the superoxide anion in the pyrogallol
      assay. The reagent also inhibited superoxide anion production in a dose-dependent
      manner in a cell-free oxidase-activating system. Translocation of the cytosolic
      respiratory burst oxidase components, the 47- and 65-kDa proteins, to membranes
      was suppressed by the reagent in intact cells stimulated with phorbol ester.
      Gabexate mesilate also reduced arachidonic acid-induced translocation of the
      components to the membrane fraction in the cell-free system. These results
      demonstrate that gabexate mesilate suppresses superoxide anion production by
      reducing the translocation of the 47- and 65-kDa proteins to the plasma membrane.

PMID- 8749320
TI  - Identification of histidine 31 and cysteine 95 in the active site of self
      incompatibility associated S6-RNase in Nicotiana alata.
AB  - S-RNase is associated with the gametophytic self-incompatibility of flowering
      plants in Solanaceae and, on the basis of sequence homology, belongs to the RNase
      T2 family. To identify the active site residues in S-RNase, Nicotiana alata S6
      RNase was studied by chemical modification. S6-RNase was inactivated with
      iodoacetic acid under conditions similar to those used for the inactivation of
      RNase T2. No inactivation took place in the presence of 2'GMP. Analysis of
      carboxymethylated S6-RNase revealed that the S-carboxymethylation of Cys95 caused
      inactivation of the enzyme and that the two histidine residues corresponding to
      two essential histidine residues of RNase T2 remained intact. Treatment of S6
      RNase with diethyl pyrocarbonate (DEPC) resulted in loss of enzyme activity, and
      the enzyme was protected from inactivation in the presence of 2'GMP. The
      ethoxycarbonylated residues in DEPC-inactivated S6-RNase were analyzed by mass
      spectrometry, which also provided structural information on sugar moieties
      attached to Asn27 and Asn37. His31 was modified with DEPC in the absence of 2'GMP
      and was not modified in its presence. His31 and His91 are conserved in all
      members of the RNase T2 family sequenced so far, but Cys95 is not conserved in
      all known Solanaceae S-RNases. These results suggest that His31, possibly
      together with His91, corresponding to His115 at the active site of RNase T2, is
      essential to the function of S6-RNase, but Cys95 is not essential though its S
      carboxymethylation causes inactivation.

PMID- 8749321
TI  - Characterization of a thermostable lysine-specific metalloendopeptidase from the
      fruiting bodies of a basidiomycete, Grifola frondosa.
AB  - A zinc-metalloendopeptidase, MEP, capable of catalyzing specific cleavage of acyl
      lysine bonds (-X-Lys-) in polypeptides has been purified 212-fold in a yield of
      24.7% from the fruiting bodies of Grifola frondosa, which is a popular edible
      mushroom called "MAITA-KE" in Japan. The purified enzyme consists of a single
      polypeptide chain with an apparent molecular mass of 20 kDa and a pI value of
      7.46, contains 1 atom of zinc/molecule and can be inactivated with EDTA or 1,10
      phenanthroline. Treatment of MEP with EDTA affords an apoenzyme, whose activity
      can be fully restored by the addition of Mn2+, Zn2+, Ca2+, or Co2+. Prominent
      features of MEP are its remarkable heat stability and its high affinity for beta
      D-glucans and chitin. It hydrolyzes proteins maximally at pH 9-10, liberating
      only lysylpeptides. Polylysine and lysine copolymers with alanine, phenylalanine,
      or glutamic acid can serve as good substrates. Lysylalanine was liberated from
      bovine insulin and its oxidized B chain by the action of MEP. Mass spectrometric
      analysis by Frit-FAB MS of the fragments generated from horse heart cytochrome c
      presented unambiguous evidence to corroborate the specificity of MEP for acyl
      lysine bonds.

PMID- 8749322
TI  - Dominant role of the second heat shock element in expression of the HSP70-1 gene
      in rat liver after whole body hyperthermia.
AB  - We investigated the regulatory expression of the HSP70-1 gene in rat liver after
      whole body hyperthermia (rectal temperature of 42 degrees C for 30 min). After
      heat treatment, HSP70-1 mRNA showed a peak at 1 h, and its protein product began
      to increase at 3 h. Under these conditions, we identified cis-acting elements
      involved in the regulatory expression of the HSP70-1 gene by in vivo genomic
      footprinting. We observed that the second heat shock element (HSE-2; -201 to 
      178) was clearly protected from methylation by dimethyl sulfate in parallel with
      the increase in HSP70-1 mRNA. On the contrary, the most proximal HSE-1 (-120 to 
      101) was protected only slightly. Furthermore, the flanking regions of HSE-2,
      that is, an NF-kappa B-like element on the upstream side and a GC box on the down
      stream side were also protected simultaneously in accordance with the induced
      expression of the HSP70-1 gene. Gel mobility shift assays with nuclear extracts
      from rat liver at 30 min after heat treatment showed maximal DNA binding activity
      equally with oligonucleotides containing HSE-1 and HSE-2, respectively, and also
      demonstrated the participation of heat shock factor-1 (HSF1) in both cases. These
      results suggest that, in addition to HSF1, other regulatory factors might be
      involved in the dominant protection of HSE-2 in the promoter of the HSP70-1 gene
      in rat liver after whole body hyperthermia.

PMID- 8749323
TI  - The roles played by the D2 and D3 domains of recombinant human thrombomodulin in
      its function.
AB  - Thrombomodulin (TM) is composed of five domains. We investigated the roles of the
      sixth epidermal growth factor (EGF)-like structure (E6) in the second domain (D2)
      and of an O-glycosylation site rich domain (D3) in the function of TM in more
      detail using deletion analysis. Two soluble mutants of TM, TMD123 and TMD12, and
      three deletion mutants lacking respectively 6, 16, and 38 C-terminal residues of
      the E6 portion, TMD12 delta 6, TMD12 delta 16, and TMD12 delta 38, were expressed
      in COS cells and purified. The results of protein C-activating cofactor assay
      showed that TMD12 delta 6, TMD12 delta 16, and TMD12 delta 38, which lack the C
      terminal region, had remarkably weak cofactor activities in comparison with
      TMD123 (9.1, 1.4, and 1.1% of TMD123 activity, respectively). Similar findings
      were obtained for anticoagulant activity. These findings indicate that the last
      loop structure in E6 is required for full activity of recombinant human TM. We
      also determined in vivo stabilities of TMD12, TMD123, and TMD12 delta 6 in a
      pharmacokinetic study in rats. TMD12 and TMD12 delta 6, which lack the D3 domain,
      exhibited increased clearance (about twice that of D123). This finding suggested
      that the D3 domain of TM plays an important role in stabilizing TM in vivo.

PMID- 8749324
TI  - Lysine-49-phospholipases A2 from Trimeresurus flavoviridis venom are membrane
      acting enzymes.
AB  - Basic proteins I and II (BP-I and BP-II) isolated from the venom of Trimeresurus
      flavoviridis (Habu snake) are isozymes of highly active Asp-49 phospholipase A2
      (Asp-49-PLA2) and classified into the group Lys-49-PLA2. BP-II was found to
      elicit a strong contraction of guinea pig ileum, and this activity was inhibited
      completely by 1 microM indomethacin, an inhibitor of the arachidonate cascade. BP
      II was inactive in the Ca(2+)-free medium, and p-bromphenacylated His-48-BP-II
      was also inactive. BP-II exhibited no binding affinity for the cells expressing
      PLA2 receptors. These results indicated that the contraction elicited by BP-II is
      due to the hydrolytic action of BP-II, liberating arachidonic acid from the ileum
      phospholipid biomembranes. In spite of its limited lipolytic activities (av. 0.9%
      of Asp-49-PLA2) against monomers and micelles of synthetic phospholipids, BP-II
      hydrolyzed considerably strongly the phospholipids in the artificial bilayer
      vesicles. Arachidonic acid released from liposomes of beta-arachidonoyl-gamma
      stearoyl-L-alpha-phosphatidylcholine was determined by HPLC, and the activity of
      BP-II was estimated to be about 75% as compared to Asp-49-PLA2. Liposomes
      encapsulating carboxyfluorescein exhibited a strong dye-leakage induced by BP-II
      in a concentration-dependent manner, only in the Ca(2+)-containing buffer. The
      net result from all these observations was that BP-II, a Lys-49-PLA2, is an
      enzyme that hydrolyzes the membrane phospholipids. In contrast to BP-II, BP-I was
      found to be considerably weak in hydrolyzing membrane phospholipids, although its
      activities were distinct. BP-I and BP-II share a common sequence with the sole
      exception of Asp-67 (BP-I) and Asn-67 (BP-II) in the aligned sequences. This
      implies that the amino acid at position 67 of Lys-49-PLA2s is the residue
      required for discriminatory recognition of beta-arachidonoyl-phospholipid
      membranes.

PMID- 8749325
TI  - Function of RNH-1/14-3-3 beta gene in cellular differentiation and proliferation.
AB  - It has recently been reported that the members of 14-3-3 protein family
      participate in cell cycle control and associate with Raf, Bcr, Bcr-Abl, and
      polyomavirus middle tumor antigen (MT) as modulators of signal transduction.
      During cDNA cloning for the 17-kDa neuronal differentiation factor (K2 factor)
      secreted from rat hepatoma Kagura-2 (K2) cells from a K2 cDNA library using rat
      prepronerve growth factor (prepro NGF) cDNA as a probe, we obtained RNH-1 (rat
      NGF homologue) clone, which was identified as 14-3-3 beta cDNA, but not K2
      factor, although no significant homology is present between 14-3-3 beta and
      prepro NGF cDNAs. RNH-1/14-3-3 beta gene was markedly expressed as a 2.9-kb mRNA
      in K2 cells and in newborn rat brain tissue. In PC12 cells the expression of this
      gene was down-regulated during the neuronal differentiation primed by NGF. The
      enforced expression of RNH-1/14-3-3 beta in PC12 and K2 cells conferred on them a
      higher sensitivity to NGF for neuronal differentiation and an intense growth
      ability in low serum medium, respectively. These results provide additional
      evidence that RNH-1/14-3-3 beta protein participates in cellular differentiation,
      proliferation and transformation through the signal transduction pathways of
      various growth factors.

PMID- 8749326
TI  - Fragmentation of ceruloplasmin following non-enzymatic glycation reaction.
AB  - Bovine ceruloplasmin underwent fragmentation following non-enzymatic
      glycosylation. Western blot and ELISA analyses indicated that a polyclonal rabbit
      antiserum to hexitolysine reacted with bovine ceruloplasmin after incubation with
      0.1 M glucose. The same fragmentation was seen upon exposure of the protein to a
      hydrogen peroxide bolus. Both catalase and EDTA blocked peroxide-dependent
      fragmentation. Incubation with glucose resulted in a time-dependent release of
      Cu2+. The released Cu2+ appeared to participate in a Fenton-type reaction to
      produce hydroxyl radicals, which effected the fragmentation. Hydroxyl radical
      scavengers such as thiourea, mannitol, methionine, and formate inhibited this
      cleavage. ESR spectral studies also supported participation of hydroxyl radicals.
      Inhibition by EDTA of the fragmentation induced by an H2O2 bolus also supports a
      role for copper in a Fenton-type reaction. Taken together these results suggest
      that reactive oxygen species, such as superoxide anion and H2O2, were formed by
      the Maillard reaction which led to hydroxyl radicals being produced by a copper
      dependent Fenton-type reaction. Both processes are likely to be involved in the
      fragmentation of ceruloplasmin.

PMID- 8749327
TI  - Molecular cloning and functional expression of a cDNA for rat phospholipid
      hydroperoxide glutathione peroxidase: 3'-untranslated region of the gene is
      necessary for functional expression.
AB  - A full-length cDNA clone for phospholipid hydroperoxide glutathione peroxidase
      (PHGPx) was isolated from a rat brain. The cDNA was 0.761 kb in length and
      encoded 170 amino acids, which included a TGA-encoded selenocysteine at residue
      46. The protein has a calculated molecular mass of 19,473 Da. We succeeded in the
      transient functional expression of a full-length cDNA for PHGPx, which includes
      the 3'-UTR, in COS-7 cells at the first attempt. Deletion of the 3'-UTR prevented
      the expression of the PHGPx activity and the incorporation of [75Se]selenious
      acid into the monomeric 19.7 kDa PHGPx protein. Thus, the 3'-UTR of the cDNA for
      PHGPx was required for the functional expression of PHGPx. Northern blot analysis
      demonstrated that the mRNA for PHGPx was widely expressed in normal rat tissues,
      especially in the testis. The mRNA levels of PHGPx in the cultured cells such as
      hepatomas, neuronal cells, nephroblastoma, and mammary myo-epithelial cells were
      higher than those of the tissues. The ratio of PHGPx to cytosolic glutathione
      peroxidase (cGPx) was significantly high in the testis and relatively high in the
      cultured cells. The mRNA levels of PHGPx in tissues were lower than those of
      cGPx.

PMID- 8749328
TI  - Regulation of vitamin D-responsive gene expression by fluorinated analogs of
      calcitriol in rat osteoblastic ROB-C26 cells.
AB  - We compared the activation of vitamin D-responsive genes by 24,24
      difluorocalcitriol [F2-1 alpha,25(OH)2D3] and 26,26,26,27,27,27
      hexafluorocalcitriol [F6-1 alpha,25(OH)2D3] with that by calcitriol [1
      alpha,25(OH)2D3] in rat osteoblastic ROB-C26 cells. F2-1 alpha,25(OH)2D3 and F6-1
      alpha, 25(OH)2D3 were ten times more potent than 1 alpha,25(OH)2D3 in inducing
      the expression of 1 alpha, 25(OH)2D3-24-hydroxylase (24-OHase) mRNA 6 h after
      adding vitamin D compounds. The lower affinity of these two fluorinated analogs
      compared with that of 1 alpha,25(OH)2D3 for vitamin D binding protein in serum
      (serum DBP) seemed to be partly involved in their increased ability to activate
      the 24-OHase gene. A time course study revealed that the expression of the 24
      OHase and osteopontin mRNAs in the cells incubated with 1 alpha, 25(OH)2D3 and F2
      1 alpha,25(OH)2D3 attained maximal levels at 6 h for 24-OHase mRNA and 18 h for
      osteopontin mRNA, the both decreased thereafter. On the contrary, F6-1
      alpha,25(OH)2D3 increased the expression of 24-OHase and osteopontin
      exponentially until 72 h. While F2-1 alpha,25(OH)2[1 beta-3H]D3 was catabolized
      quickly by ROB-C26 cells, F6-1 alpha,25(OH)2[1 beta-3H]D3 was slowly and
      quantitatively converted into putative 26,26,26,27,27,27-hexafluoro-23S-hydroxy[1
      beta-3H]calcitriol (F6-1 alpha,23S,25(OH)3[1 beta-3H]D3). This may explain why
      the time-course profiles of the accumulation of mRNAs for 24-OHase and
      osteopontin differed in the cells exposed to the fluorinated analogs. In addition
      to the longer retention, unknown up-regulating mechanisms appeared to be involved
      in the exponential activation of the 24-OHase and osteopontin genes induced by F6
      1 alpha,25(OH)2D3.

PMID- 8749329
TI  - The fourth armadillo repeat of plakoglobin (gamma-catenin) is required for its
      high affinity binding to the cytoplasmic domains of E-cadherin and desmosomal
      cadherin Dsg2, and the tumor suppressor APC protein.
AB  - Plakoglobin is a member of a protein family with a repeated amino acid motif, the
      armadillo repeat, and is a cytoplasmic protein found in both adherens junctions
      and desmosomes. Plakoglobin has been shown to form distinct complexes with
      cadherins or desmosomal cadherins. Also, plakoglobin has been shown to complex
      with APC, the tumor suppressor gene product. Recently we isolated a cDNA clone
      encoding plakoglobin lacking the fourth armadillo repeat of the original 13
      repeat protein [Ozawa et al. (1995) J. Biochem. 118, 836-840]. In this study, we
      established an in vitro assay system to study the molecular interaction of
      plakoglobin with cadherins, the APC gene product, and alpha-catenin.
      Establishment of the system and cloning of an alternate form of plakoglobin cDNA
      allowed us to examine the biological activity of plakoglobin lacking the fourth
      armadillo repeat. Experiments with the bacterially expressed 12-repeat
      plakoglobin revealed that the protein binds to E-cadherin, desmoglein (Dsg2), and
      APC with lower affinity than the 13-repeat form does. Consistent with the
      observation that the affinity of alpha-catenin for these two alternate forms was
      similar, we found amino acid residues 104 to 145 of plakoglobin, the residues
      present in both isoforms, are sufficient for its binding to alpha-catenin.

PMID- 8749330
TI  - Significance of Thr182 in the nucleotide-exchange and GTP-hydrolysis reactions of
      the alpha subunit of GTP-binding protein Gi2.
AB  - The crystal structures of the GTP- and GDP-bound alpha subunits of heterotrimeric
      GTP-binding proteins were recently determined, and a conserved Thr residue in the
      G2 (linker 2) region of the alpha subunits, which corresponds to Thr182 in Gi2
      alpha, was deduced to interact with the gamma-phosphate of GTP and Mg2+. To
      investigate biochemically the significance of the Thr residue, we produced a
      mutant Gi2 alpha, in which Thr182 was substituted for Ala (T182A), in Escherichia
      coli. The rate of guanosine 5'-(gamma-thio)tri-phosphate (GTP gamma S) binding to
      T182A was higher than that to the wild-type Gi2 alpha, especially with a high
      concentration (10 mM) of Mg2+. The rate of dissociation of bound GDP from T182A
      was also much faster than that from the wild-type with the high Mg2+
      concentration. Moreover, T182A had much lower GTPase activity than the wild-type,
      like the gip mutant (R179C) of Gi2 alpha found in human endocrine tumors. The
      ability of T182A to interact with beta gamma subunits and membrane-bound
      receptors was the same as that of the wild-type alpha subunit. T182A could take
      on a GTP-bound active conformation, as judged from its sensitivity to tryptic
      digestion. These results indicated that Thr182 plays an important role not only
      in the Mg(2+)-sensitive GDP-GTP exchange reaction but also in the GTPase activity
      of Gi2 alpha. The T182A mutant of Gi2 alpha, characterized by the faster GDP
      release and the slower GTP hydrolysis, would be a novel mutant that retains the
      ability to interact with receptors and beta gamma subunits.

PMID- 8749331
TI  - Post-lens tear film thinning in rigid gas permeable lenses.
AB  - An attempt is made to gain a greater understanding of lens binding during
      overnight wear. To do this, a mathematical model is used to investigate the
      motion of a rigid gas permeable (RGP) lens normal to the eye surface, when the
      eye is closed. Graphs of the displacement of the lens as a function of time are
      computed for different lens designs. The rate of apical tear film thinning is
      found to depend upon the central fitting relation, with lenses that are fitted
      flatter giving the highest rate of thinning. The model also suggests the
      relevance of other factors such as eyelid muscle tension and tear-layer
      composition during sleep to the clinical phenomenon of lens binding.

PMID- 8749332
TI  - Patient preferences and comparative ocular responses to rigid and soft contact
      lenses.
AB  - Patient preferences and ocular responses were compared between rigid and soft
      contact lenses by randomly fitting 32 neophyte subjects with a rigid lens in 1
      eye and a soft lens in the contralateral eye. Twenty-seven of 32 subjects
      completed the 3-month study and 16 subjects were willing to continue for an
      additional 3-month extension. Subjects preferred the comfort and handling of the
      soft lens but preferred the vision provided by the rigid lens and initially its
      ease of maintenance. There was also a marked preference for the soft lens when
      all aspects of lens wear were compared. Objectively, the rigid lenses were
      responsible for more ocular changes than the soft lenses. Palpebral aperture
      sizes of the rigid gas permeable (RGP) wearing eyes decreased significantly (0.5
      mm; p < 0.05) compared to the soft lens wearing eyes. The incidence of corneal
      staining was significantly greater in the rigid lens wearing eye (50% RGP vs. 22%
      soft) but limbal injection was greater in the soft lens wearing eye (18% soft vs.
      6% RGP). Refractive sphere, cylinder, and corneal astigmatism decreased in the
      rigid lens wearing eye after 3 months. This daily wear clinical trial has shown a
      marked subjective preference for wearing soft lenses with fewer short-term ocular
      effects.

PMID- 8749333
TI  - Effects of luminance, contrast, and blur on visual acuity.
AB  - Although previous investigations have reported that changes in background
      luminance, stimulus contrast, and dioptric blur can each affect visual acuity
      independently, it has not been shown how these three variables interact to
      influence visual acuity. This is a particularly important issue if one is
      interested in predicting how individuals with different refractive
      characteristics will be able to perform acuity-based tasks in degraded visual
      environments with low background lighting and contrast levels. To investigate
      these relations, we conducted a series of experiments in which measurements of
      visual acuity were obtained for four subjects using Landolt C targets of varying
      contrast at several background luminances for levels of blur between 0 and 8
      diopters (D). Our results show that visual acuity is significantly affected by
      all three factors, and that their effects are essentially additive. At all
      luminance and contrast levels, the reduction in visual acuity is greatest for
      dioptric blur up to 2.0 D, with a more gradual reduction in visual acuity for
      dioptric blur of greater than 2.0 D. At all blur and luminance levels, visual
      acuity decreases gradually for contrast levels down to 20%, and decreases sharply
      for lower contrast levels. Over the range of background luminances we tested
      (75.0 to 0.075 cd/m2), visual acuity decreases linearly with reductions in
      luminance. The additive effects of dioptric blur, contrast, and luminance provide
      a basis for predicting visual acuity-related task performance for individuals in
      different visual environments. For example, an individual with 6/6 (20/20) visual
      acuity under high luminance-high contrast conditions will fall to 6/18 (20/60)
      acuity for low luminance conditions and 6/30 (20/100) for low luminance-low
      contrast conditions. Similarly, an individual with an uncorrected visual acuity
      of 6/30 (20/100) under optimal conditions will fall to approximately 6/120
      (20/400) under low luminance conditions and 6/240 (20/800) under low luminance
      low contrast conditions.

PMID- 8749334
TI  - Clinical findings before the onset of myopia in youth. I. Ocular optical
      components.
AB  - PURPOSE: A study was conducted to identify variables that were different in
      children who were emmetropic and became myopic and in children who remained
      emmetropic. METHODS: A cohort of initially emmetropic children had eye and vision
      examinations at 6-month intervals for a period of 3 years. Ocular optical
      components were measured by keratometry and ultrasonography. Crystalline lens
      power was calculated using Bennett's formulas. RESULTS: There was a tendency for
      keratometer power of both principal meridians to be greater in the became-myopic
      group than in the remained-emmetropic group. Axial length to corneal radius
      (AL/CR) ratio was significantly greater in the became-myopic group than in the
      remained-emmetropic group. The variable with the highest sensitivity and
      specificity was the AL/CR ratio using the horizontal meridian corneal radius.
      CONCLUSIONS: Greater corneal powers and greater AL/CR ratios are risk factors for
      youth onset myopia.

PMID- 8749335
TI  - Medications used to prevent migraine headaches and their potential ocular adverse
      effects.
AB  - We present a detailed review of the medications used in the USA, Canada, and the
      United Kingdom for the prevention of migraine and the potential ocular adverse
      effects associated with the use of these medications. Those drugs that are
      administered for the purpose of reducing the frequency or severity of migraine
      attacks are classified according to whether they act on the cerebral vasculature
      primarily at serotonin (5-HT2) receptors (e.g., methysergide, cyproheptadine, and
      pizotyline), beta adrenergic (primarily beta-2) receptors (e.g., propranolol and
      timolol), via central nervous system (CNS) adrenergic (alpha-2) receptors (e.g.,
      clonidine), or calcium channels (e.g., flunarizine). The roles and mechanisms of
      action of tricyclic antidepressants (e.g., amitriptyline) and nonsteroidal anti
      inflammatory drugs (NSAIDs) in the prophylactic management of migraine are also
      discussed, along with possible pharmacogenetic differences in the kinetics of
      action of some of these drugs. The general indications, contraindications, and
      potential ocular and systemic adverse effects of each class of drugs is reviewed
      and presented along with the references to original literature on these effects.

PMID- 8749336
TI  - Predicting success with orthokeratology lens wear: a retrospective analysis of
      ocular characteristics.
AB  - PURPOSE: Orthokeratology procedures suffer from lack of predictability in the
      response of individuals. To identify factors contributing to this, we have
      retrospectively studied a range of ocular parameters in patients with varying
      outcomes from orthokeratology lens wear. EXPERIMENTAL DESIGN: Three groups were
      studied: an experimental group (9 subjects wearing Contex OK-3 design
      orthokeratology contact lenses), and 2 control groups [10 rigid gas permeable
      (RGP) contact lens wearers and 10 non-contact lens wearers]. Three categories
      were identified among the orthokeratology group: those responding well,
      moderately, or poorly to orthokeratology lens wear. Measurements included
      subjective refraction, intraocular distances, corneal thickness, ocular rigidity,
      and epithelial fragility. RESULTS: When comparing the three orthokeratology
      categories, there was no significant difference for central and peripheral
      epithelial fragility and ocular rigidity. There was also no significant
      difference for any of the biometric characteristics measured. The prefitting
      spherical equivalent power was found to be significantly different between
      categories of responders (p = 0.0228), with the poor responders having the
      highest initial level of myopia. None of the measured characteristics differed
      significantly among the orthokeratology group and the two control groups.
      CONCLUSIONS: In this pilot study, the success of orthokeratology lens wear was
      not related to ocular biomechanical or biometric attributes, but it was related
      to prefitting refractive error.

PMID- 8749337
TI  - Environmental near-UV radiation and cataracts.
AB  - This report compares sunlight UV-A and UV-B fluxes in the Northeastern United
      States that reach the crystalline lens with thresholds that cause lens damage.
      The fluxes of UV-A and UV-B radiation that reach earth to penetrate the cornea
      and to reach the lens were calculated. Ten hours of continuous UV-A exposure or
      23 min of UV-B would exceed the rabbit cornea threshold for photokeratitis. The
      lens threshold would be reached by 26 h of UV-A or 245 h of UV-B continuous
      exposure. The sequence of UV-induced damage follows: (1) UV-B photokeratitis; (2)
      UV-A photokeratitis; (3) UV-A lens damage; and (4) UV-B lens damage.

PMID- 8749338
TI  - Do DEM test scores change with respect to the language? Norms for Spanish
      speaking population.
AB  - The Developmental Eye Movement (DEM) test is a clinical oculomotor test of a
      visual-verbal format which has been normalized and whose reliability and validity
      have been shown elsewhere in an English speaking population. In this paper, the
      authors provide normative data for a Spanish speaking population from ages 6 to
      11 years. Also, a comparison of results for both languages is provided. The DEM
      test appears to be highly efficient and not linguistically related for all
      subjects involved in the study. Results in that age bracket are clinically the
      same. For age 6 years, although results are not similar (Spanish subjects are
      significantly slower), the ratio is similar in both groups. The DEM test appears
      to be reliable; its results could be used in any population regardless of the
      language.

PMID- 8749339
TI  - A new method for quantification of the dynamics of dark adaptation.
AB  - A new method of quantifying the dynamics of the human dark adaptation function is
      presented. This method is based on nonlinear regression analysis and allows the
      derivation of a number of clinically useful indices of dark adaptation ability.
      The analysis method is applied to literature data describing the effect of ageing
      on dark adaptation and to clinical data from a retinitis pigmentosa patient.
      Ageing was seen to decrease the rate of adaptation in the cone portion of the
      dark adaptation function, and to have little effect on the rate of adaptation in
      the rod portion of the dark adaptation function. One case of retinitis pigmentosa
      was associated with increased rod and cone thresholds but little change in the
      rate of adaptation of the cone portion of the dark adaptation function. It is
      suggested that this analysis method may offer advantages in quantifying changes
      in dark adaptation dynamics.

PMID- 8749340
TI  - Stability of the precorneal tear film in Chinese, African, Indian, and Caucasian
      eyes.
AB  - The stability of the precorneal tear film was measured noninvasively in normal
      subjects from four diverse ethnic groups (Chinese, Africans, Indians, and
      Caucasians) all resident in the west of Scotland. Statistically significant
      differences were found to exist among the groups. The respective mean ( +/- SD)
      tear stabilities were: 9.8 s (3.9), 11.8 s (5.9), 16.4 s (6.9), and 19.9 s (8.3).
      Subjects were selected from an age range of 17 to 45 years.

PMID- 8749341
TI  - Parallel-testing infinity balance. Instrument and technique for the parallel
      testing of binocular vision.
AB  - Routine refraction involves a series of tests during which changes carried out in
      the latter part of the routine may alter parameters already considered to have
      been fixed. These earlier parameters, although thought to have been fixed, are
      therefore not always valid. No binocular testing device is presently available
      which allows the practitioner to be aware of how the changing of one parameter
      affects the others. The Parallel-Testing Infinity Balance (PTIB) has been
      designed to provide that tool. It is an adaptation of the Turville Infinity
      Balance. It has the potential for binocular balancing, including suppression,
      astigmatic distortion, image size and shape variation, and vertical and
      horizontal imbalances. There follows a discussion of its design and use.

PMID- 8749342
TI  - Use of a ball-bearing to facilitate goniolens rotation.

PMID- 8749343
TI  - Congenital ocular motor apraxia with torsional oscillations: a case report.
AB  - Congenital ocular motor apraxia (C-OMA) is an infrequently reported eye movement
      disorder associated with malformation or delayed maturation of the brain.
      Patients with C-OMA are unable to initiate voluntary horizontal saccades. This
      results in characteristic head thrusts into the desired field of gaze to
      compensate for the lack of saccadic ability. Careful examination of an 8-year-old
      Hispanic male revealed uncoordinated eye movements, lack of voluntary saccades,
      head thrusts, and gross/fine motor delays all consistent with congenital ocular
      motor apraxia. Torsional oscillations that resembled rotary nystagmus were also
      present. These have not been previously reported in association with C-OMA.
      Because young patients with this condition may appear to have cortical blindness,
      C-OMA is an important differential to be aware of in making a diagnosis.

PMID- 8749344
TI  - Surgical revision after failed lateral ankle reconstruction.
AB  - Ten patients were treated with revision ankle ligament reconstruction from 1989
      through 1994 for recurrent symptomatic instability of the ankle after failure of
      a primary reconstruction. There were seven female and three male patients with an
      average age of 28 years. In four patients, symptoms developed shortly after the
      first reconstruction and in six patients, symptoms developed 56.2 months
      (average) after the initial reconstruction surgery. The average follow-up was 14
      months after revision surgery. All patients had significant functional impairment
      before surgery and all failed to respond to conservative treatment, which
      included physical therapy and bracing. Seven revision ligament reconstructions
      included the use of a tendon graft, including the peroneus brevis, accessory
      peroneus, plantaris, and peroneus tertius. All revision procedures were
      modifications of the Elmslie procedure, (Sammarco-DiRaimondo). In addition, three
      Brostrom-Gould procedures were performed. The average follow-up was 31 months.
      All patients had clinical stability of the ankle following revision
      reconstruction. Nine patients (90%) returned to their previous functional level.
      After surgery, two patients had minimal pain and mononeuritis multiplex developed
      in one patient. The outcome of revision ankle ligament reconstruction compares
      favorably with reports for primary ankle reconstruction. Revision ankle
      reconstruction is a good procedure for selected patients. It is an appropriate
      option when conservative therapy fails to relieve recurrent symptoms of ankle
      instability following primary reconstruction.

PMID- 8749345
TI  - Split posterior tibial tendon transfer through the interosseus membrane in
      spastic equinovarus deformity.
AB  - The split posterior tibial tendon transfer procedure was first reported by Green
      for correction of equinovarus hindfoot deformity in patients with cerebral palsy.
      A modification of the split posterior tibial tendon transfer combined with an
      Achilles tendon lengthening is described in 17 children (21 procedures) with a
      minimum follow-up of 3 years. This modified technique is indicated in young
      children with a continuously spastic posterior tibial tendon to correct a dynamic
      equinovarus. It restores active dorsiflexion when the anterior tibial and
      extensor muscles are weak. The anterior half of the split tibialis posterior is
      transferred through the interosseus membrane to the dorsum of the foot. Excellent
      or good results and two poor results were noted after a mean follow-up of 29
      months. In the patients with an excellent or good result, marked improvement of
      their equinovarus foot deformity in stance and swing phase of gait was seen. In
      two patients, the procedure failed because of technical errors.

PMID- 8749346
TI  - Morton's interdigital neuroma: a comprehensive treatment protocol.
AB  - One hundred fifteen patients with signs and symptoms of Mortons' interdigital
      neuroma were studied in an attempt to evaluate the efficacy of a staged treatment
      program. The first stage consisted of patient education, footwear modifications,
      and metatarsal head relief. The second stage consisted of a steroid/local
      anesthetic injection into the affected interspace. The third stage was surgical
      excision of the inflamed interdigital nerve. Overall, 97 of 115 patients (85%)
      believed that they had improved with the treatment program. Twenty-four patients
      (21%) eventually required surgical excision of the nerve and 23 of 24 patients
      (96%) had satisfactory results. The results of the staged treatment protocol were
      very satisfactory and patient satisfaction was high.

PMID- 8749347
TI  - A technique to evaluate foot function during the stance phase of gait.
AB  - A technique to measure foot function during the stance phase of gait is
      described. Advantages of the method include its three-dimensional approach with
      anatomically based segment coordinate systems. This allows variables such as
      ground reaction forces and center of pressure location to be expressed in a local
      foot coordinate system, which gives more anatomical meaning to the interpretation
      of results. Application of the measurement technique to case examples of patients
      with rheumatoid arthritis demonstrated its ability to discriminate normal from
      various levels of pathological function. Future studies will utilize this
      technique to study the impact of pathology and treatment on foot function.

PMID- 8749349
TI  - Properties of shoe insert materials related to shock wave transmission during
      gait.
AB  - The influence of the mechanical characteristics of certain insole materials in
      the generation and transmission of heel strike impacts while walking was studied.
      Three insole materials were selected according to their mechanical
      characteristics under heel strike impacts. The selection of materials has made it
      possible to distinguish the effect of rigidity and loss tangent in the
      transmission of heel strike impacts. A lower rigidity and a high loss tangent
      have been shown to reduce the transmission of impacts to the tibia. A low
      rigidity was seen to significantly increase the transmission of impacts from
      tibia to forehead.

PMID- 8749348
TI  - Nonoperative treatment of metatarsophalangeal joint synovitis.
AB  - The results of nonoperative treatment of metatarsophalangeal (MP) joint synovitis
      in 13 patients without known rheumatologic conditions (15 joints) were reviewed.
      Average duration of forefoot pain was 4 +/- 3 months (range 0.5-12 months),
      except for one patient who had pain for 30 months. The second MP joint was
      involved in nine cases (60%), and the third was involved in six cases (40%).
      Examination revealed tenderness and palpable fullness of the MP joint in all
      cases; painful dorsal drawer sign was present in 10 cases (67%), adjacent
      interdigital tenderness in six cases (40%), and hammertoe deformity in eight
      cases (53%). Treatment included intra-articular corticosteroid injection and
      rocker-sole show modification to limit MP joint dorsiflexion. At follow-up
      evaluation (18 +/- 9 months, range 4-26 months), the involved MP joint was
      asymptomatic in nine joints (60%), improved or almost asymptomatic in five joints
      (33%), and operated in one (7%) joint. Two of seven (29%) joints not initially
      associated with hammertoe developed a mild hammertoe deformity from time of
      diagnosis to follow-up. In conclusion, nonoperative treatment can be effective
      for MP joint synovitis, and the incidence of progressive hammertoe deformity in
      successfully treated cases is low.

PMID- 8749350
TI  - Paradoxical transcutaneous oxygen response to cutaneous warming on the plantar
      foot surface: a caution for interpretation of plantar foot TcPO2 measurements.
AB  - We examined the effect of cutaneous warming on the transcutaneous oxygen
      measurement (TcPO2) at standard locations below the knee, on the dorsal foot, on
      the plantar right great toe, and on the plantar surface under the second
      metatarsal head of 656 diabetic and 16 nondiabetic subjects. All subjects
      underwent a directed medical history, physical examination, and neurovascular
      lower extremity evaluation and assessment of autonomic neuropathy. Associations
      between autonomic neuropathy and TcPO2 were tested using two-way analysis of
      variance and multiple linear regression. An unexpected, statistically significant
      fall in TcPO2 occurred with cutaneous warming from 37 degrees C to 44 degrees C
      on the plantar great toe surface that did not differ by presence of autonomic
      neuropathy, or the presence of diabetes (mean change: -8.82 mmHG, 95% confidence
      interval [CI]: -7.70 to -9.93). The TcPO2 measured at the plantar metatarsal head
      site also fell with cutaneous warming from 37 degrees C to 44 degrees C (mean
      change: -9.67 mmHG, 95% CI: -7.75 to -11.59). As expected, the TcPO2 increased
      with cutaneous warming from 37 degrees C to 44 degrees C on the dorsal foot site
      (mean rise:= 35.61 mmHg, 95% CI: 34.18 to 37.04). The mean TcPO2 at any site did
      not differ by presence of autonomic neuropathy at either 37 degrees C or 44
      degrees C. We conclude that cutaneous warming leads to a paradoxical fall in
      TcPO2 on the plantar foot surface that does not depend on the presence of
      autonomic neuropathy or diabetes. Caution in interpretation of ambient versus
      warmed plantar TcPO2 values is recommended.

PMID- 8749351
TI  - Calcification of the tibialis posterior tendon: a case report and literature
      review.
AB  - The tibialis posterior muscle and tendon are subject to a number of pathological
      conditions and injuries that have recently received much attention in the
      literature. Because of its function as a main stabilizer of the subtalar complex
      against hindfoot valgus and forefoot pronation, the mechanical demand on the
      posterior tibial tendon is high. Problems with dislocation, tenosynovitis,
      rupture, and laceration have all been described with this tendon. In this report,
      we present a case of dysfunction of the posterior tibial tendon associated with
      chronic tendinitis and intratendinous calcifications. After removal of the
      calcifications, the patient became asymptomatic and returned to work. Proposed
      etiologies of these calcifications are discussed.

PMID- 8749352
TI  - Extraskeletal osteosarcoma: an unusual presentation as tarsal tunnel syndrome.
AB  - Tarsal tunnel syndrome is a compressive neuropathy caused by intrinsic or
      extrinsic pressure on the posterior tibial nerve or one of its terminal branches.
      A mass in association with tarsal tunnel syndrome is most likely a benign tumor
      or tumor-like condition, although a more malignant tumor must be in the
      differential diagnosis. We report an unusual case of an extraskeletal
      osteosarcoma causing tarsal tunnel syndrome.

PMID- 8749353
TI  - Fracture of the tarsal navicular associated with calcaneonavicular coalition: a
      case report.
AB  - Fracture of the navicular occurred in a 23-year-old male with unilateral
      cartilaginous calcaneonavicular coalition. Inversion sprain of the left foot
      caused the longitudinal navicular fracture next to the coalition. En bloc
      resection from the beak of the calcaneus to the fracture line of the navicular
      including the calcaneonavicular coalition was performed, and a short leg cast was
      applied for 10 days. Four weeks after surgery, he returned to his preinjury level
      of activity and job as a long-distance truck driver. Two years and 3 months after
      surgery, he was totally asymptomatic and had gained a full range of subtalar
      motion. He had no peroneal spasm or recurrence of the coalition.

PMID- 8749354
TI  - Subtalar joint dislocations.
AB  - Dislocations of the subtalar joint are rare injuries. The anatomy,
      pathophysiology, treatment, and prognosis of subtalar joint dislocations have
      been well described in the literature. The purpose of this paper is to review the
      current literature on subtalar joint dislocations, as well as outline those
      aspects of the anatomy, pathomechanics, and treatment pertinent to care of the
      patient with subtalar joint dislocation. In addition, complications and obstacles
      to reduction are described. Subtalar joint dislocations, although not common,
      have increased in frequency over the last decade. Generally, they can be treated
      successfully with closed reduction and a short period of cast immobilization. The
      majority of patients will suffer some disability with subtalar joint stiffness
      the primary complaint. Associated intra-articular fractures increase the risk of
      posttraumatic arthrosis.

PMID- 8749355
TI  - Triple arthrodesis for diabetic peritalar neuropathy.

PMID- 8749356
TI  - Silastic single-stem implants in the treatment of hallux rigidus.

PMID- 8749358
TI  - Ribosomal proteins and elongation factors.
AB  - Structural work on the translation machinery has recently undergone rapid
      progress. It is now known that six out of nine ribosomal proteins have an RNA
      binding fold, and two domains of elongation factors Tu and G have very similar
      folds. In addition, the complex of EF-Tu with a GTP analogue and Phe-tRNA(Phe)
      has a structure that overlaps exceedingly well with that of EF-G-GDP. These
      findings obviously have functional implications.

PMID- 8749359
TI  - Protein phosphatases.
AB  - Protein phosphatases are signal transducing enzymes that dephosphorylate cellular
      phosphoproteins. The recently determined crystal structures of protein tyrosine
      and serine/threonine phosphatases reveal that these proteins adopt distinct
      structures and catalyze dephosphorylation reactions by means of different
      enzymatic mechanisms. Insights into the basis for substrate specificity and
      enzyme regulation can also be gained from these crystal structures.

PMID- 8749360
TI  - Recognition at the cell surface: recent structural insights.
AB  - In the past few years, structural biology has begun to reveal details of some of
      the receptors and associated interactions responsible for protein-mediated
      recognition events at the cell surface. Recent data span the fields of cytokine
      receptor interactions, cell adhesion molecules and viral infection.

PMID- 8749361
TI  - Bacterial chemotaxis: a field in motion.
AB  - Many different types of studies are being combined to provide an increasingly
      detailed picture of the bacterial chemotaxis system. The structures of
      periplasmic receptors and a cytoplasmic response regulator, along with structures
      of domains of a membrane receptor, a receptor-modifying enzyme and a cytoplasmic
      histidine kinase, have been determined. These structures provide a basis for
      other work which is likely to open up new structural avenues.

PMID- 8749362
TI  - Enzymes of nucleotide synthesis.
AB  - Seven new structures reported during the past year have increased dramatically
      our understanding of enzymes involved in nucleotide de novo synthesis and
      salvage. Several new protein folds have been identified, including at least four
      prototypes for new functional families. The construction of larger structures
      from modules with a catalytic function is a recurring theme. Our understanding of
      the structural basis of allostery will be enriched by the three new structures of
      allosteric enzymes.

PMID- 8749363
TI  - Di-iron-carboxylate proteins.
AB  - Di-iron centers bridged by carboxylate residues and oxide/hydroxide groups have
      so far been seen in four classes of proteins involved in dioxygen chemistry or
      phosphoryl transfer reactions. The dinuclear iron centers in these proteins are
      coordinated by histidines and additional carboxylate ligands. Recent structural
      data on some of these enzymes, combined with spectroscopic and kinetic data, can
      now serve as a base for detailed mechanistic suggestions. The di-iron sites in
      the major class of hydroxylase-oxidase enzymes, which contains ribonucleotide
      reductase and methane monooxygenase, show significant flexibility in the geometry
      of their coordination of three or more carboxylate groups. This flexibility,
      combined with a relatively low coordination number, and a buried environment
      suitable for reactive oxygen chemistry, explains their efficient harnessing of
      the oxidation power of molecular oxygen.

PMID- 8749364
TI  - Cytochrome P450.
AB  - Since 1993, three new cytochrome P450 X-ray structures have been determined,
      giving a total of four known structures. Two of the new structures are in the
      substrate-free form and one is substrate-bound. These new structures, together
      with a wealth of mutagenesis studies on various P450s, have provided considerable
      information on what structural features control substrate specificity in P450s.
      In addition, some important insights into the catalytic mechanism have been made.

PMID- 8749365
TI  - NAD-binding domains of dehydrogenases.
AB  - The nicotinamide adenine dinucleotide (NAD)-binding domains of dehydrogenases,
      containing a conserved double beta-alpha-beta-alpha-beta motif, are common
      structural feature of many enzymes that bind NAD, nicotinamide adenine
      dinucleotide phosphate (NADP) and related cofactors. Features of this folding
      pattern that create a natural binding site for such molecules have been
      described. The domain continues to appear in many structures, in the form of a
      common core with different peripheral additions or variations. Other structures
      that bind NAD and related molecules use entirely different topologies, although,
      in many, a phosphate group appears at the N terminus of an alpha helix.
      Ferredoxin reductase seems to show convergent evolution, containing a single beta
      alpha-beta motif that is similar both in its structure and in its interactions
      with the ligand to a region in dehydrogenases.

PMID- 8749366
TI  - Proteins at atomic resolution.
AB  - Experimental advances in data collection, including bright sources, cryogenic
      cooling and two-dimensional detectors, have made it tractable to record data to
      beyond 1.2 A for several proteins, yielding high-accuracy models and fine details
      of structure. For small metalloproteins, atomic-resolution data have enabled ab
      initio solution of the phase problem.

PMID- 8749368
TI  - Light-harvesting mechanisms in purple photosynthetic bacteria.
AB  - The processes by which photosynthetic bacteria capture light and transfer the
      energy to the reaction centre continue to be studied using an array of
      methodologies, both physical and biological. With the publication this year of
      the crystal structure of the LH2 complex from Rhodopseudomonas acidophila and the
      projection structure of the LH1 complex from Rhodospirillum rubrum, structural
      models now exist for all the components in the bacterial photosynthetic
      apparatus.

PMID- 8749369
TI  - Structure of bacterial luciferase.
AB  - The generation of light by living organisms such as fireflies, glow-worms,
      mushrooms, fish, or bacteria growing on decaying materials has been a subject of
      fascination throughout the ages, partly because it occurs without the need for
      high temperatures. The chemistry behind the numerous bioluminescent systems is
      quite varied, and the enzymes that catalyze the reactions, the luciferases, are a
      large and evolutionarily diverse group. The structure of the best understood of
      these intriguing enzymes, bacterial luciferase, has recently been determined,
      allowing discussion of features of the protein in structural terms for the first
      time.

PMID- 8749370
TI  - Regulatory GTPases.
AB  - The past year has witnessed a tremendous increase in our understanding of the
      structures and interactions of the GTPases. The highlights include crystal
      structures of G alpha subunits, as well as the first complex between a GTPase
      (Rap1A) and an effector molecule (c-Raf1 Ras-binding domain). In the field of
      elongation factors (EFs), three very important structures have been determined:
      EF-G, the ternary complex of EF-Tu.GTP with aminoacyl-tRNA, and the EF-Tu.EF-Ts
      complex.

PMID- 8749371
TI  - The scope of antibody catalysis.
AB  - New strategies for hapten design have led to antibodies that catalyze reactions
      by increasingly complex mechanisms and with large increases in catalytic rate.
      Rational design has also been used to elicit catalytic antibodies for difficult
      chemical transformations as well as reactions for which no enzyme is known. These
      experiments have demonstrated the chemical potential of large combinatorial
      libraries that have been given appropriate mechanistic instruction.

PMID- 8749372
TI  - What makes a binding site a binding site?
AB  - Organic probe molecules have recently been used to define hydrophobic binding
      sites on the surface of proteins. It appears that the presence of water on the
      surface of a protein plays a crucial role in the interaction between that protein
      and its binding site.

PMID- 8749373
TI  - How nature deals with stereoisomers.
AB  - All natural proteins are composed of L-amino acids and are inherently chiral. The
      properties of both L- and chemically synthesized D-amino acids are identical
      except in optically asymmetric interactions. Structural studies of D-I racemic
      mixtures of crystallographic interest are discussed. The review also gives some
      recent examples of stereospecificity: how L-proteins deal with L- or D-substrates
      and how enzymes can function as racemases. Two particular examples of
      stereoselectivity are then discussed.

PMID- 8749374
TI  - Proteins.

PMID- 8749375
TI  - Catalysis and regulation.

PMID- 8749376
TI  - Arthropod evolution: Brine shrimp add salt to the stew.

PMID- 8749377
TI  - Synaptic plasticity: A molecular mechanism for metaplasticity.

PMID- 8749378
TI  - Nuclear pores: David and Goliath in nuclear transport.

PMID- 8749379
TI  - Appetite control: Does leptin lighten the problem of obesity?

PMID- 8749380
TI  - Somatic hypermutation: Another piece in the hypermutation puzzle.

PMID- 8749381
TI  - Neural patterning: A forward role for hedgehog.

PMID- 8749382
TI  - Plant photomorphogenesis: a green light for cryptochrome research.

PMID- 8749383
TI  - Motile systems: Tubulin-based motility races ahead.

PMID- 8749384
TI  - Cystic fibrosis: How do CFTR mutations cause cystic fibrosis?

PMID- 8749385
TI  - Pattern formation: The link between ovary and embryo.

PMID- 8749386
TI  - Left-right asymmetry: The embryo's one-sided genes.

PMID- 8749387
TI  - Cell-cell signaling: The ins and outs of receptor tyrosine phosphatases.

PMID- 8749388
TI  - Neural coding: The enigma of the brain.

PMID- 8749389
TI  - Antigen presentation: Kissing cousins exchange CLIP.

PMID- 8749390
TI  - Dissection of a retrovirus envelope protein reveals structural similarity to
      influenza hemagglutinin.
AB  - BACKGROUND: The amino-acid sequences of retroviral envelope proteins contain a '4
      3 hydrophobic repeat', with hydrophobic amino acids spaced every four and then
      every three residues, characteristic of sequences that form coiled coils. The 4-3
      hydrophobic repeat is located in the transmembrane subunit (TM) of the retroviral
      envelope protein, adjacent to the fusion peptide, a region that inserts into the
      host bilayer during the membrane-fusion process. A 4-3 hydrophobic repeat region
      in an analogous position of the influenza hemagglutinin protein is recruited to
      extend a three-stranded coiled coil during the conformational change to the
      fusion-competent state. To determine the conformation of the retroviral TM
      subunit and the role of the 4-3 hydrophobic repeat, we constructed soluble
      peptide models of the envelope protein of Moloney murine leukemia virus (MMLV).
      RESULTS: The region of the MMLV TM protein external to the lipid envelope (the
      ectodomain) contains a stably folded, trimeric, protease-resistant core. As
      predicted, an alpha-helical segment spans the 4-3 repeat. A cysteine-rich region
      carboxy-terminal to the 4-3 repeat confers a dramatic increase in stability and
      displays a unique disulfide bonding pattern. CONCLUSIONS: Our results demonstrate
      that the MMLV TM subunit can fold into a stable and distinct species in the
      absence of the receptor-binding 'surface' co-subunit (SU) of the envelope
      complex. As the SU subunit is readily shed from the surface of the virus, we
      conclude that the TM subunit structure forms the core of the MMLV membrane-fusion
      machinery, and that this structure, like the fusion-active conformation of
      influenza hemagglutinin, contains a three-stranded coiled coil adjacent to the
      fusion peptide.

PMID- 8749391
TI  - The core of the mammalian centriole contains gamma-tubulin.
AB  - BACKGROUND: The microtubule network, upon which transport occurs in higher cells,
      is formed by the polymerization of alpha and beta tubulin. The third major
      tubulin isoform, gamma tubulin, is believed to serve a role in organizing this
      network by nucleating microtubule growth on microtubule-organizing centers, such
      as the centrosome. Research in vitro has shown that gamma tubulin must be
      restored to stripped centrioles to regenerate the centrosomal functions of
      duplication and microtubule nucleation. RESULTS: We have re-examined the
      localization of gamma tubulin in isolated and in situ mammalian centrosomes using
      a novel immunocytochemical technique that preserves antigenicity and morphology
      while allowing increased accessibility. As expected, alpha tubulin was localized
      in cytoplasmic and centriolar barrel microtubules and in the associated
      pericentriolar material. Foci of gamma tubulin were observed at the periphery of
      the organized pericentriolar material, as reported previously, often near the
      termini of microtubules. A further and major location of gamma tubulin was a
      structure within the proximal end of the centriolar barrel. The distributions
      were complementary, in that alpha tubulin was excluded from the core of the
      centriole, and gamma tubulin was excluded from the microtubule barrel.
      CONCLUSIONS: We have shown that gamma tubulin is localized both in the
      pericentriolar material and in the core of the mammalian centriole. This result
      suggests that gamma tubulin has a role in the centriolar duplication process,
      perhaps as a template for growth of the centriolar microtubules, in addition to
      its established role in the nucleation of astral microtubules.

PMID- 8749392
TI  - Protein kinase C is regulated in vivo by three functionally distinct
      phosphorylations.
AB  - BACKGROUND: Protein kinase Cs are a family of enzymes that transduce the plethora
      of signals promoting lipid hydrolysis. Here, we show that protein kinase C must
      first be processed by three distinct phosphorylations before it is competent to
      respond to second messengers. RESULTS: We have identified the positions and
      functions of the in vivo phosphorylation sites of protein kinase C by mass
      spectrometry and peptide sequencing of native and phosphatase-treated kinase from
      the detergent-soluble fraction of cells. Specifically, the threonine at position
      500 (T500) on the activation loop, and T641 and S660 on the carboxyl terminus of
      protein kinase C beta II are phosphorylated in vivo. T500 and S660 are
      selectively dephosphorylated in vitro by protein phosphatase 2A to yield an
      enzyme that is still capable of lipid-dependent activation, whereas all three
      residues are dephosphorylated by protein phosphatase 1 to yield an inactive
      enzyme. Biochemical analysis reveals that protein kinase C autophosphorylates on
      S660, that autophosphorylation on S660 follows T641 autophosphorylation, that
      autophosphorylation on S660 is accompanied by the release of protein kinase C
      into the cytosol, and that T500 is not an autophosphorylation site. CONCLUSIONS:
      Structural and biochemical analyses of native and phosphatase-treated protein
      kinase C indicate that protein kinase C is processed by three phosphorylations.
      Firstly, trans-phosphorylation on the activation loop (T500) renders it
      catalytically competent to autophosphorylate. Secondly, a subsequent
      autophosphorylation on the carboxyl terminus (T641) maintains catalytic
      competence. Thirdly, a second autophosphorylation on the carboxyl terminus (S660)
      regulates the enzyme's subcellular localization. The conservation of each of
      these residues (or an acidic residue) in conventional, novel and atypical protein
      kinase Cs underscores the essential role for each in regulating the protein
      kinase C family.

PMID- 8749393
TI  - A family of phosphoinositide 3-kinases in Drosophila identifies a new mediator of
      signal transduction.
AB  - BACKGROUND: Mammalian phosphoinositide 3-kinases (PI 3-kinases) are involved in
      receptor-mediated signal transduction and have been implicated in processes such
      as transformation and mitogenesis through their role in elevating cellular
      phosphatidylinositol (3,4,5)-trisphosphate. Additionally, a PI 3-kinase activity
      which generates phosphatidylinositol 3-phosphate has been shown to be required
      for protein trafficking in yeast. RESULTS: We have identified a family of three
      distinct PI 3-kinases in Drosophila, using an approach based on the polymerase
      chain reaction to amplify a region corresponding to the conserved catalytic
      domain of PI 3-kinases. One of these family members, PI3K_92D, is closely related
      to the prototypical PI 3-kinase, p110 alpha; PI3K_59F is homologous to Vps34p,
      whereas the third, PI3K_68D, is a novel PI 3-kinase which is widely expressed
      throughout the Drosophila life cycle. The PI3K_68D cDNA encodes a protein of 210
      kDa, which lacks sequences implicated in linking p110 PI 3-kinases to p85 adaptor
      proteins, but contains an amino-terminal proline-rich sequence, which could bind
      to SH3 domains, and a carboxy-terminal C2 domain. Biochemical analyses
      demonstrate that PI3K_68D has a novel substrate specificity in vitro, restricted
      to phosphatidylinositol and phosphatidylinositol 4-phosphate, and is unable to
      phosphorylate phosphatidylinositol (4,5)-bisphosphate, the implied in vivo
      substrate for p110. CONCLUSIONS: A family of PI 3-kinases in Drosophila,
      including a novel class represented by PI3K_68D, is described. PI3K_68D has the
      potential to bind to signalling molecules containing SH3 domains, lacks p85
      adaptor-binding sequences, has a Ca(2+)-independent phospholipid-binding domain
      and displays a restricted in vitro substrate specificity, so it could define a
      novel signal transduction pathway.

PMID- 8749394
TI  - Physical interaction between a novel domain of the receptor Notch and the
      transcription factor RBP-J kappa/Su(H).
AB  - BACKGROUND: The mammalian transcription factor RBP-J kappa binds to the DNA
      sequence motif CGTGGGAA and is involved in the regulation of gene expression; for
      example, it plays a part in the transactivation of viral and cellular genes by
      Epstein-Barr virus nuclear antigen-2. The Drosophila homologue of RBP-J kappa is
      the product of the Suppressor of Hairless (Su(H)) gene. Su(H) is a neurogenic
      gene that acts downstream of Notch, which encodes a cell-surface receptor.
      Furthermore, in the mouse, the phenotypes of homozygous mutant Notch1 embryos are
      very similar to those of homozygous mutant RBP-J kappa embryos. Recent studies,
      using the yeast two-hybrid system, have led to the suggestion that the
      CDC10/ankyrin-like repeats of the Drosophila Notch protein interact with the
      Su(H) protein. RESULTS: We searched for proteins that interact with mouse RBP-J
      kappa using the yeast two-hybrid system, and in this way identified a short
      intracellular region (mRAM23) of the mouse Notch1 protein that lacks any known
      sequence motif. In vitro interaction studies, using proteins fused to glutathione
      S-transferase, showed that RBP-J kappa and Su(H) bind directly to the RAM23
      regions of mouse Notch1 and Drosophila Notch, respectively. Immunoprecipitation
      analysis showed that RBP-J kappa and the mRAM23 region of mouse Notch1 also
      interact in vivo. Further studies, including site-directed mutagenesis
      experiments, narrowed down the region of mouse Notch1 that interacts with RBP-J
      kappa. The results indicate that this region is less than 50 amino-acid residues
      in length, and lies immediately downstream of the transmembrane region.
      CONCLUSIONS: We show that the transcription factor RBP-J kappa/Su(H) interacts
      directly with a novel intracellular domain of the cell-surface receptor Notch.
      RBP-J kappa/Su(H) does not appear to interact with Notch via the CDC10/ankyrin
      repeats implicated in previous studies.

PMID- 8749395
TI  - Extent and character of circadian gene expression in Drosophila melanogaster:
      identification of twenty oscillating mRNAs in the fly head.
AB  - BACKGROUND: Although mRNAs expressed with a circadian rhythm have been isolated
      from many species, the extent and character of circadianly regulated gene
      expression is unknown for any animal. In Drosophila melanogaster, only the period
      (per) gene, an essential component of the circadian pacemaker, is known to show
      rhythmic mRNA expression. Recent work suggests that the encoded Per protein
      controls its own transcription by an autoregulatory feedback loop. Per might also
      control the rhythmic expression of other genes to generate circadian behavior and
      physiology. The goals of this work were to evaluate the extent and character of
      circadian control of gene expression in Drosophila, and to identify genes
      dependent on per for circadian expression. RESULTS: A large collection of
      anonymous, independent cDNA clones was used to screen for transcripts that are
      rhythmically expressed in the fly head. 20 of the 261 clones tested detected
      mRNAs with a greater than two-fold daily change in abundance. Three mRNAs were
      maximally expressed in the morning, whereas 17 mRNAs were most abundant in the
      evening--when per mRNA is also maximally expressed (but when the flies are
      inactive). Further analysis of the three 'morning' cDNAs showed that each has a
      unique dependence on the presence of a light-dark cycle, on timed feeding, and on
      the function of the per gene for its oscillation. These dependencies were
      different from those determined for per and for a novel 'evening' gene. Sequence
      analysis indicated that all but one of the 20 cDNAs identified previously
      uncloned genes. CONCLUSIONS: Diurnal control of gene expression is a significant
      but limited phenomenon in the fly head, which involves many uncharacterized
      genes. Diurnal control is mediated by multiple endogenous and exogenous
      mechanisms, even at the level of individual genes. A subset of circadianly
      expressed genes are predominantly or exclusively dependent on per for their
      rhythmic expression. The per gene can therefore influence the expression of genes
      other than itself, but for many rhythmically expressed genes, per functions in
      conjunction with external inputs to control their daily expression patterns.

PMID- 8749397
TI  - Cell lineage patterns and homeotic gene activity during Antirrhinum flower
      development.
AB  - BACKGROUND: Homeotic genes controlling the identity of flower organs have been
      characterized in several plant species. To determine whether cells expressing
      these genes are specified to follow particular developmental fates, we have
      studied the pattern of cell lineages in developing flowers of Antirrhinum. Each
      flower has four whorls of organs, and progenitor cells of these can be marked at
      particular stages of development using a temperature-sensitive transposon. This
      allows the cell lineages in the flower to be followed, as well as giving
      information about rates of cell division. RESULTS: We show here that, prior to
      the emergence of organ primordia, cells in the floral meristem have not been
      allocated organ identities. After this time, lineage restrictions arise between
      whorls, correlating with the onset of expression of genes that control organ
      identity. A further lineage restriction appears slightly later on, between the
      dorsal and ventral surfaces of the petal. Our results further suggest that the
      rates of cell division fluctuate during key stages of meristern development,
      perhaps as a consequence of meristem-identity gene expression. CONCLUSIONS: The
      patterns of lineage restriction and organ-identity gene expression in early
      floral meristems are consistent with some cells being allocated specific
      identities at about this stage of development. Plant cells cannot move relative
      to each other, so lineage restrictions in plants may reflect particular
      orientations and/or rates of growth at boundary regions.

PMID- 8749396
TI  - Serrate and wingless cooperate to induce vestigial gene expression and wing
      formation in Drosophila.
AB  - BACKGROUND: The appendages of insects, like the limbs of vertebrates, grow out of
      the body wall after the establishment of a proximo-distal axis among a group of
      primordial cells. In Drosophila, the wing develops in the limbless larva from one
      of the imaginal discs of the thorax, which give rise to the adult epidermis. The
      earliest identified requirement in wing development is for the induction of
      vestigial (vg) gene expression at the interface between ventral cells and dorsal
      cells of the wing disc. It has been proposed that this event requires two
      reciprocal signals--one from the dorsal to the ventral cells and the other from
      the ventral to the dorsal cells--which trigger vg expression at the presumptive
      wing margin and hence initiate the development of the wing tissue. RESULTS: We
      have identified four genes--Serrate (Ser), wingless (wg), Notch and Suppressor of
      Hairless (Su(H))--whose activity is required during the second and early third
      larval instars for the expression of vg. Analysis of the functions and patterns
      of expression of these genes at the time of the inductive event indicates that
      the Ser protein acts as a dorsal signal, and the Wg protein as a ventral signal
      for the induction of vg expression. Furthermore, the expression of both Ser and
      Wg is sufficient to trigger ectopic wing development in the wing disc and leg
      discs. The product of the Notch gene, which encodes a receptor, is also required
      for this event and we suggest that its role is to integrate the inputs of Ser and
      Wg. CONCLUSIONS: We show that the induction of vg, which initiates wing
      development in Drosophila, requires the combined activities of Ser, wg and Notch.
      Based on the patterns of expression and requirements for Ser and wg in this
      process, we propose that Ser is a dorsal signal and that Wg is a ventral signal,
      and that their combination at the dorso-ventral interface activates the Notch
      receptor and leads to vg expression.

PMID- 8749398
TI  - [Acute viral hepatitis (type A)].

PMID- 8749399
TI  - [Hepatitis B].

PMID- 8749400
TI  - [Type C hepatitis].

PMID- 8749401
TI  - [Hepatitis E].

PMID- 8749402
TI  - [Hepatitis F virus].

PMID- 8749403
TI  - [Gianotti disease and Gianotti-Crosti syndrome].

PMID- 8749404
TI  - [Adenovirus hepatitis].

PMID- 8749405
TI  - [Viral hepatitis].

PMID- 8749406
TI  - [Yellow fever, measles, rubella].

PMID- 8749407
TI  - [Gas-containing liver abscess, hepatic gas gangrene].

PMID- 8749408
TI  - [Pyogenic liver abscess].

PMID- 8749409
TI  - [Hepatic aspergillosis].

PMID- 8749410
TI  - [Hepatic amebiasis, amebic liver abscess].

PMID- 8749411
TI  - [Hepatic toxocariasis].

PMID- 8749412
TI  - [Echinococcosis of the liver].

PMID- 8749413
TI  - [Hepatitis virus carrier].

PMID- 8749414
TI  - [Hepatic ascariasis].

PMID- 8749415
TI  - [Falciform ligament abscess].

PMID- 8749416
TI  - [Hepatic candidiasis].

PMID- 8749417
TI  - [Parasitic liver disease].

PMID- 8749419
TI  - [Hepatic cryptococcosis].

PMID- 8749418
TI  - [Clonorchiasis].

PMID- 8749420
TI  - [Liver cryptosporidiosis].

PMID- 8749421
TI  - [Tuberculosis and tuberculoma of the liver].

PMID- 8749422
TI  - [Infectious diseases of the liver due to protozoa].

PMID- 8749423
TI  - [Hepatic mycosis, mycotic liver abscess].

PMID- 8749424
TI  - [Fascioliasis].

PMID- 8749425
TI  - [Toxoplasmosis of the liver].

PMID- 8749426
TI  - [Schistosomiasis japonica of the liver].

PMID- 8749427
TI  - [Liver abscess (solitary liver abscess, multiple liver abscess, subcapsular liver
      abscess].

PMID- 8749428
TI  - [Hepatic actinomycosis].

PMID- 8749429
TI  - [Schistosoma haematobium].

PMID- 8749430
TI  - [Rickettsiosis].

PMID- 8749431
TI  - [Hepatic listeriosis].

PMID- 8749432
TI  - [Leptospirosis, Weil's disease].

PMID- 8749433
TI  - [Epidemic of hepatitis in Sashima].

PMID- 8749434
TI  - [Neonatal hepatitis].

PMID- 8749435
TI  - [Delta hepatitis].

PMID- 8749436
TI  - [Early syphilitic hepatitis].

PMID- 8749437
TI  - [Oriental cholangiohepatitis].

PMID- 8749438
TI  - [Non-A, non-B, non-C viral hepatitis].

PMID- 8749439
TI  - [Hepatitis induced by HIV (human immunodeficiency virus].

PMID- 8749440
TI  - [Herpesvirus hepatitis].

PMID- 8749441
TI  - [Child-Pugh classification in liver cirrhosis].

PMID- 8749442
TI  - [Alcoholic liver cirrhosis].

PMID- 8749443
TI  - [Cirrhosis of the liver due to hepatitis virus].

PMID- 8749444
TI  - [Cirrhosis of the liver and its definition, classification and clinical feature].

PMID- 8749445
TI  - [Benign cirrhotic nodule, macronodular cirrhosis].

PMID- 8749446
TI  - [Parasitic liver cirrhosis].

PMID- 8749447
TI  - [Splenomegalic liver cirrhosis].

PMID- 8749448
TI  - [Autoimmune liver cirrhosis].

PMID- 8749449
TI  - [Juvenile cirrhosis].

PMID- 8749450
TI  - [Juvenile fatty cirrhosis].

PMID- 8749451
TI  - [Cardiac cirrhosis].

PMID- 8749452
TI  - [Liver cirrhosis associated with metabolic disorders].

PMID- 8749453
TI  - [Compensated cirrhosis, decompensated cirrhosis].

PMID- 8749454
TI  - [Secondary biliary cirrhosis].

PMID- 8749455
TI  - [Chronic hepatitis].

PMID- 8749456
TI  - [Drug-induced cirrhosis, chemical cirrhosis].

PMID- 8749457
TI  - [Acute-on-chronic liver failure].

PMID- 8749458
TI  - [Eck fistula syndrome].

PMID- 8749459
TI  - [Subacute hepatitis (SAH)].

PMID- 8749460
TI  - [Hepatic encephalopathy].

PMID- 8749461
TI  - [Liver failure (hepatic failure)].

PMID- 8749462
TI  - [Acute liver failure].

PMID- 8749463
TI  - [Fulminant hepatitis].

PMID- 8749464
TI  - [Liver failure after severe trauma].

PMID- 8749465
TI  - [Post-operative liver failure].

PMID- 8749466
TI  - [Late onset hepatic failure (LOHF)].

PMID- 8749467
TI  - [Alpha-fetoprotein producing hepatocellular carcinoma, AT-III producing
      hepatocellular carcinoma].

PMID- 8749468
TI  - [Fibrolamellar carcinoma of the liver].

PMID- 8749469
TI  - [Liver cell dysplasia].

PMID- 8749470
TI  - [von Meyenburg's complex (biliary microhamartoma)].

PMID- 8749471
TI  - [Hepatocellular carcinoma of accessory liver].

PMID- 8749472
TI  - [Ectopic liver and ectopic hepatocellular carcinoma].

PMID- 8749473
TI  - [Adrenal rest tumor of the liver].

PMID- 8749474
TI  - [Lipomatous tumors (lipoma, angiomyolipoma, myelolipoma, focal fatty change) in
      the liver].

PMID- 8749475
TI  - [Hepatic lymphangiomatosis and its related tumors and tumor-like conditions].

PMID- 8749476
TI  - [Malignant fibrous histiocytoma of the liver].

PMID- 8749477
TI  - [Mantle cell lymphoma of the liver].

PMID- 8749478
TI  - [Undifferentiated sarcoma of the liver].

PMID- 8749479
TI  - [Yolk sac tumor of the liver].

PMID- 8749480
TI  - [Malignant germ cell tumor of the liver].

PMID- 8749481
TI  - [Malignant lymphoma of liver].

PMID- 8749482
TI  - [Atypical adenomatous hyperplasia].

PMID- 8749483
TI  - [Inflammatory pseudotumor of the liver].

PMID- 8749484
TI  - [Hepatoblastoma].

PMID- 8749485
TI  - [Mesenchymal hamartoma of the liver].

PMID- 8749486
TI  - [Hepatic teratoma, malignant teratoma].

PMID- 8749487
TI  - [Pseudolymphoma of the liver].

PMID- 8749488
TI  - [Hemangioma and hyalinized hemangioma of the liver].

PMID- 8749489
TI  - [Hemangiopericytoma of the liver].

PMID- 8749490
TI  - [Hepatic angiosarcoma].

PMID- 8749491
TI  - [Malignant mixed tumor of the liver].

PMID- 8749492
TI  - [Eosinophilic granuloma of the liver].

PMID- 8749493
TI  - [Hepatocellular carcinoma with cirrhosis].

PMID- 8749494
TI  - [Cholangiocellular carcinoma associated with liver cirrhosis].

PMID- 8749495
TI  - [Osteosarcoma of the liver].

PMID- 8749496
TI  - [Hepatocellular carcinoma (HCC)].

PMID- 8749497
TI  - [Hepatocellular carcinoma (scirrhous type)].

PMID- 8749498
TI  - [Hepatocellular carcinoma in adenomatous hyperplasia].

PMID- 8749499
TI  - [Hepatic tumors resembling hepatocellular carcinoma].

PMID- 8749500
TI  - [Primary hepatic choriocarcinoma].

PMID- 8749501
TI  - [Neurofibroma of the liver, schwannoma of the liver].

PMID- 8749502
TI  - [Primary fibroma of the liver, primary fibrosarcoma of the liver].

PMID- 8749503
TI  - [Liver adenoma and hepatobiliary cystadenoma].

PMID- 8749504
TI  - [Histiocytoma of the liver].

PMID- 8749505
TI  - [Signet ring cell carcinoma of the intrahepatic bile duct].

PMID- 8749506
TI  - [Cholangiocarcinoma].

PMID- 8749507
TI  - [Intrahepatic bile duct adenocarcinoma].

PMID- 8749508
TI  - [Adenosquamous carcinoma of the liver].

PMID- 8749509
TI  - [Intrahepatic sarcomatoid cholangiocarcinoma].

PMID- 8749510
TI  - [Intrahepatic biliary papillomatosis].

PMID- 8749511
TI  - [Mucinous cholangiocarcinoma, mucus producing carcinoma].

PMID- 8749512
TI  - [Squamous cell carcinoma of the intrahepatic bile duct].

PMID- 8749513
TI  - [Hepatic granuloma].

PMID- 8749514
TI  - [Mucinous cholangiocarcinoma].

PMID- 8749515
TI  - [Mucoepidermoid carcinoma of the liver or the intrahepatic bile duct].

PMID- 8749516
TI  - [Osteoclast-like giant cell tumor of the liver].

PMID- 8749517
TI  - [Primary leiomyoma of the liver].

PMID- 8749518
TI  - [Carcinoma of the hilar bile ducts].

PMID- 8749519
TI  - [Epithelioid hemangioendothelioma].

PMID- 8749520
TI  - [Borderline lesions of adenomatous hyperplasia and hepatocellular carcinoma].

PMID- 8749521
TI  - [Hepatocellular carcinoma of nodular type].

PMID- 8749522
TI  - [Primary hepatic carcinoid tumor].

PMID- 8749523
TI  - [Paraneoplastic syndrome of hepatocellular carcinoma].

PMID- 8749524
TI  - [Primary hepatic tumor].

PMID- 8749525
TI  - [Primary hepatic sarcoma].

PMID- 8749526
TI  - [Primary hepatic leiomyosarcoma and rhabdomyosarcoma].

PMID- 8749527
TI  - [Sclerosing hepatic carcinoma].

PMID- 8749528
TI  - [Well-differentiated hepatocellular carcinoma].

PMID- 8749529
TI  - [Combined hepatocellular and cholangiocarcinoma].

PMID- 8749530
TI  - [Cholangiocellular carcinoma (intrahepatic bile duct carcinoma)].

PMID- 8749531
TI  - [Small liver cancer].

PMID- 8749532
TI  - [Infantile hemangioendothelioma of the liver].

PMID- 8749533
TI  - [Hepatic tumor in children].

PMID- 8749534
TI  - [Metastatic liver tumor].

PMID- 8749535
TI  - [Hepatocellular carcinoma of specific developmental type (massive type,
      pedunculated type, extrahepatic type, diffuse type, and intra-bile duct
      developmental type)].

PMID- 8749536
TI  - [Peripheral type of cholangiocarcinoma without intrahepatic bile duct
      dilatation].

PMID- 8749537
TI  - [Liver neoplasms due to Thorotrast].

PMID- 8749538
TI  - [Sarcomatoid carcinoma].

PMID- 8749539
TI  - [Hepatocellular carcinoma originated in the caudate lobe].

PMID- 8749540
TI  - [Primary hormone-producing hepatic tumor].

PMID- 8749541
TI  - [Undifferentiated hepatic carcinoma].

PMID- 8749542
TI  - [Aagenaes syndrome].

PMID- 8749543
TI  - [Alagille syndrome].

PMID- 8749544
TI  - [Antimitochondrial antibody negative primary biliary cirrhosis].

PMID- 8749545
TI  - [Byler disease].

PMID- 8749546
TI  - [Microfilament dysfunction (severe familial cholestasis in North American Indian
      children)].

PMID- 8749547
TI  - [Nielsen syndrome].

PMID- 8749548
TI  - [Summerskill syndrome].

PMID- 8749549
TI  - [Zellweger syndrome].

PMID- 8749550
TI  - [Familial benign chronic intrahepatic cholestasis].

PMID- 8749551
TI  - [Cholangiopathy after orthotopic liver transplantation: Rejection
      cholangiopathy].

PMID- 8749552
TI  - [Dysmorphogenesis of intrahepatic bile duct].

PMID- 8749553
TI  - [Primary sclerosing cholangitis (PSC)].

PMID- 8749554
TI  - [Primary biliary cirrhosis (PBC) (symptomatic, asymptomatic)].

PMID- 8749555
TI  - [PBC-CAH overlapping syndrome].

PMID- 8749556
TI  - [Intrahepatic cholestasis associated with neonatal small intestinal obstruction].

PMID- 8749557
TI  - [Cholestasis in congenital heart diseases (hypoplastic left heart syndrome,
      aortic coarctation)].

PMID- 8749558
TI  - [Vanishing bile duct syndrome].

PMID- 8749559
TI  - [Idiopathic adulthood ductopenia].

PMID- 8749560
TI  - [Intrahepatic cholestasis in internal medicine].

PMID- 8749561
TI  - [Intrahepatic cholestasis in infants and children].

PMID- 8749562
TI  - Prevalence of SLE: higher or lower?

PMID- 8749563
TI  - DNA repair deficiency in systemic lupus erythematosus; cause or consequence of
      disease and implications for management.

PMID- 8749564
TI  - Genetics of systemic lupus erythematosus.

PMID- 8749565
TI  - The mosaic of SLE-II: highlights of the fourth international conference on
      systemic lupus erythematosus--March 1995.

PMID- 8749566
TI  - Special report: adjusted lupus prevalence. Results of a marketing study by the
      Lupus Foundation of America.
AB  - There are many estimates of the prevalence of systemic lupus erythematosus. These
      range from a high of 1:245 to 1:1000 from numerous worldwide epidemiologic
      studies. In a departure from scientific procedure the Lupus Foundation of America
      recently completed an inexpensive marketing study which produced three findings.
      Firstly, that lupus awareness in the USA was about 86%, much higher than many
      other immunologic illnesses. Secondly, that many people have been told by their
      physicians that they have the lupus, and considering that data, that over 1.4
      million people in the USA have the disease. Lastly, that the prevalence of the
      disease, by unsubstantiated claim, would be a very high 1 in 177 patients. The
      overall conclusion is that more people are being told that they have the disease
      lupus than previously expected. Self-reporting studies are notoriously inaccurate
      as the criteria for the disease are not verified, indicating that the numbers
      derived from this study may not be true.

PMID- 8749567
TI  - Prevalence of self-reported physician-diagnosed systemic lupus erythematosus in
      the USA.
AB  - The objective of this study was to estimate the prevalence of self-reported
      physician-diagnosed systemic lupus erythematosus (SLE) in the USA. During the
      conduct of an epidemiologic study of systemic sclerosis (scleroderma), 16 607
      randomly selected telephone numbers in the continental USA were called to recruit
      controls. All potentially eligible women were asked 'Have you ever been told by a
      doctor that you have lupus or SLE'? Of 4034 women aged 18 and above who completed
      telephone screening, 15 stated they had a physician diagnosis of SLE,
      corresponding to a prevalence of 372 cases per 100 000 (95% confidence intervals:
      208, 614). After review of available medical records in six cases, however, the
      prevalence of 'validated' SLE was revised to 124 cases per 100 000 (95%
      confidence intervals: 40, 289). In conclusion, these data suggest that the
      prevalence of SLE in the USA may be up to three to 10-fold greater than
      previously estimated. Based on 1990 census data, we would project that over 275
      000 women aged 18 and above have SLE in the USA.

PMID- 8749568
TI  - Immunomodulating effects of synchronised plasmapheresis and intravenous bolus
      cyclophosphamide in systemic lupus erythematosus.
AB  - Recent studies have suggested that synchronised plasmapheresis and intravenous
      pulse cyclophosphamide therapy reduce disease activity in SLE patients. The aim
      of the present study was to examine the immunomodulating effects of this therapy
      and compare it with changes seen with cyclophosphamide alone. Four patients with
      active SLE were studied. Two were treated with synchronised therapy and two
      received cyclophosphamide only for up to 26 weeks. Disease activity was measured
      by the SLE disease activity index (SLEDAI). Immunological studies were performed
      immediately prior to each treatment. Patients in both treatment groups improved
      as reflected by a fall in mean SLEDAI scores: synchronised therapy 33.5 to 11;
      cyclophosphamide only 13.5 to 4.5. Following synchonised therapy only there was a
      prompt and sustained increase in the mean percentage of CD8+ cells (20.8 to 54.8)
      which resulted in a fall in the CD4:CD8 ratio (1.95 to 0.62). With both treatment
      modalities there was a fall in the proportion of CD20+ cells (B lymphocytes)
      (synchronised therapy 10.5 to 3.2; cyclophosphamide only 5.6 to 2.2). However,
      only synchronised therapy resulted in a fall in the in vitro production of
      immunoglobulins which was unchanged or increased following cyclophosphamide
      alone. These results suggest that although both treatment modalities are
      efficacious in the treatment of active SLE they produce different
      immunomodulatory effects. Thus, both therapies reduce the number of circulating B
      lymphocytes whereas synchronised therapy also modifies cellular immunity by
      promoting the emergence of a phenotypic suppressor T lymphocyte population.

PMID- 8749569
TI  - Human T cell responses to autoantibody variable region peptides.
AB  - The origins and regulation of autoantibodies in SLE may involve idiotypic cell
      interactions. The purpose of this study was to determine if SLE patients have T
      cells reactive with the idiotopes of autoantibodies. Sequences of the variable
      regions of two DNA-binding autoantibodies (V lambda of antibody B3 and VH of 9G4)
      were selected according to the predicted location of their idiotypes defined
      previously by anti-idiotypic antibodies. The sequences were prepared as synthetic
      16mer peptides (idiopeptides). Peripheral blood mononuclear cells were prepared
      from SLE patients (n = 28) and controls (n = 13) and put into multiple
      microcultures with idiopeptide for 6 days. The frequency of responding cultures
      was determined as those incorporating thymidine at levels above the mean plus
      three standard deviations of the control cultures lacking peptide. Of the 28
      lupus patients, six responded to B3 idiopeptide and five to the 9G4 idiopeptide.
      Some patients responded to other idiopeptides, but only one normal individual
      responded to each reference peptide. The difference between the patient and
      control responses to all idiopeptides was significant by chi 2 analysis (P =
      0.025). We conclude that patients with SLE show evidence of sensitisation of T
      cells to idiotopes of autoantibodies. Such anti-idiotypic T cells could either
      provide idiotype-specific help or suppression for autoantibody responses in SLE.

PMID- 8749570
TI  - Clinical significance of phospholipid-dependent anti-beta 2-glycoprotein I (beta
      2-GPI) antibodies in systemic lupus erythematosus.
AB  - We investigated the clinical significance of IgG phospholipid-dependent anti-beta
      2-glycoprotein I (beta 2-GPI) antibodies in patients with SLE. The study
      population consisted of 140 patients with SLE. Sera were examined for IgG
      phospholipid-dependent anti-beta 2-GPI antibodies by ELISA. IgG phospholipid
      dependent anti-beta 2-GPI antibodies were detected in 21 of 140 patients (15%)
      and remained positive from 4 to 98 months. Significantly higher incidences of
      thrombosis, intrauterine fetal loss, thrombocytopenia, patients with
      antiphospholipid syndrome (APS), prolonged APTT, BFP-STS and hemolytic anemia
      were found in SLE patients with phospholipid-dependent anti-beta 2-GPI
      antibodies. Moreover, significantly lower incidences of malar rash and serositis
      were found in SLE patients with phospholipid-dependent anti-beta 2-GPI
      antibodies, and the majority of these patients satisfied four or five of the
      revised criteria items of the American Rheumatism Association. These differences
      were not observed when we compared clinical manifestations in anticardiolipin
      antibody-positive patients with those in antibody-negative patients by
      conventional ELISA. These results indicated that SLE patients with IgG
      phospholipid-dependent anti-beta 2-GPI antibodies show an unique form of SLE.

PMID- 8749571
TI  - Role of beta 2-glycoprotein I in the anticardiolipin antibody affinity for
      phospholipid in autoimmune disease.
AB  - The binding capacity to cardiolipin and the functional affinity of affinity
      purified anticardiolipin (aCL) IgG of patients with autoimmune disease have been
      compared with those of individuals with malaria and acquired immunodeficiency
      syndrome (AIDS). The binding of autoimmune IgG aCL was enhanced gradually by the
      incorporation of increasing amounts of beta 2-glycoprotein I (beta 2GPI) into the
      assay, in contrast to that of patients with infectious diseases. In addition,
      there were significant reductions of functional affinity in autoimmune disease,
      but not in malaria or in AIDS. These results indicate that beta 2GPI requirement
      for binding to the target antigen varies inversely with functional affinity in
      autoimmune disease when beta 2GPI was present, and suggest that IgG aCL are more
      heterogeneous in this type of disorder than in patients with infectious disease.

PMID- 8749572
TI  - Anticardiolipin antibodies in two elderly subpopulations.
AB  - Previous studies have reported that the prevalence of certain autoantibodies is
      nonspecifically elevated in elderly subjects due to immunoscenescence. This study
      was undertaken to assess the prevalence of anticardiolipin antibodies (aCL) in
      two elderly subpopulations: Two hundred and eighteen elderly were included in
      this study; 63 healthy elderly had a prevalence of anticardiolipin antibodies of
      zero; 155 unselected frail elderly were prospectively evaluated and the
      prevalence of anticardiolipin antibodies in this group was found to be
      significantly increased at 18.7%. Subdivision of this group into those elderly
      clinically assessed as suffering from dementia showed a prevalence of 26.5% and
      stroke a prevalence of 31.6%. Both were found to be statistically significantly
      increased when compared with both the healthy and frail elderly population.
      Subdivision of the dementia patients into those suffering from multi-infarct type
      dementia (MID) and those suffering from Alzheimer's type dementia (AD) showed an
      association of 44% and 20%, respectively. The association of MID with aCL was
      significant. This study demonstrates therefore that anticardiolipin antibodies
      are not nonspecifically elevated in elderly subjects but are significantly
      elevated in elderly subjects with strokes and multiple infarct dementia.

PMID- 8749573
TI  - Anticardiolipin antibodies and acute alcoholic intoxication.
AB  - Many clinical features have been associated with the antiphospholipid antibodies.
      In a preliminary prospective study, among 1014 consecutive patients admitted to a
      Medicine Department, 72 (7.1%) patients were found to be anticardiolipin
      antibodies (aCL) positive. Eight (11%) of these aCL positive patients had
      alcoholic intoxication. Chronic alcoholism is known to be associated with a high
      prevalence of autoimmune disorders. The objective of this study was to determine
      the prevalence of aCL in patients with acute alcoholic intoxication. Sixty two
      patients (13 women; 49 men), mean age 35 years (range 17-63 years) referred to
      the emergency care unit were studied. A control population of 62 apparently
      healthy subjects, age and sex matched, were also tested. Alcoholaemia, aCL,
      antinuclear antibodies (ANA), Venereal Disease Research Laboratory (VDRL) and
      Treponema pallidum immobilisation (TPHA) were determined. The mean alcoholaemia
      among all patients tested was 2.35 gl-1 (range 0.1-4). aCL were found positive in
      10 patients (16%); eight men and two women. Seven patients had aCL IgG level of >
      or = 15 UG PL/ml while two had IgM level of > or = 12.5 UMPL/ml. One had both
      elevated aCL IgG and IgM. Statistical analysis confirmed that aCL positivity is
      more frequently encountered in alcoholic patients compared with an age and sex
      matched population (P = 0.0298). Among alcoholic patients, 12 (19%) had ANA. Four
      of them were VDRL positive while all were TPHA negative. Two of the 62 control
      subjects were found aCL positive. From these data, it can be concluded that
      increased aCL levels are frequently associated with acute alcoholic abuse.

PMID- 8749574
TI  - Reversal of thrombocytopenia following oral anticoagulation in two patients with
      primary antiphospholipid syndrome.
AB  - We report on two patients with the primary antiphospholipid syndrome who had
      significant thrombocytopenia. In both patients platelet number improved soon
      after initiation of oral anticoagulation. Possible mechanisms for the resolution
      of thrombocytopenia are discussed.

PMID- 8749575
TI  - Development of polyarteritis nodosa in the course of inactive systemic lupus
      erythematosus.
AB  - A 63-year-old woman developed a clinical and pathological picture of
      polyarteritis nodosa (PAN). Systemic lupus erythematosus (SLE) had been diagnosed
      12 years previously, and she had been symptom and therapy-free for a decade.
      Development of 'primary' systemic vasculitis in SLE patients has rarely been
      described previously and the significance of this association remains unclear.
      The possible explanation for this transition from one connective tissue disease
      to another is discussed.

PMID- 8749576
TI  - Choroidopathy in a case of systemic lupus erythematosus.
AB  - Choroidopathy in association with systemic lupus erythematosus (SLE) has rarely
      been reported. We report a patient with SLE and choroidopathy manifested by
      bilateral multifocal, serous elevations of the neurosensory retina. Control of
      the systemic disease resulted in resolution of the serous detachment.

PMID- 8749577
TI  - Autoantibodies to calprotectin are not found in patients with systemic lupus
      erythematosus or other inflammatory rheumatic diseases.

PMID- 8749578
TI  - Aging and single versus multiple cues in source monitoring.
AB  - Participants heard words said by 2 speakers and later decided who said each word.
      The authors varied the perceptual distinctiveness of the speakers and the
      distinctiveness of the cognitive operations participants performed on the words.
      Relative to younger adults, older adults had significantly lower source
      monitoring scores when perceptual or cognitive operations conditions were similar
      but not when either cue was more distinctive. Combining cues did not affect
      source monitoring of younger adults but hurt older adults' performance relative
      to the distinctive perceptual condition. Evidently, older adults generate
      cognitive cues at the expense of encoding perceptual cues; any deficit in binding
      perceptual and semantic information disadvantages them more in source monitoring
      than in old/new recognition. There was no correlation between neuropsychological
      tests assessing frontal function and source monitoring in older adults.

PMID- 8749579
TI  - Assessing stress-buffering effects: a cautionary note.
AB  - Research on the stress-buffering functions of social support is equivocal. The
      purpose of this study was to suggest that part of the reason for these
      contradictory findings may be due to the fact that researchers have misspecified
      the relationship between stress and support. Instead of always being an effective
      coping resource, this study tested the view that there are limits to the
      beneficial effects of assistance provided by others and that beyond a certain
      level support may actually exacerbate the noxious impact of stress. Data from a
      recent nationwide survey of older adults support this more complex perspective.
      More specifically, the data suggest that although emotional support initially
      reduces the effects of chronic financial strain on depressive symptoms, further
      increments in emotional assistance are associated with increased psychological
      distress.

PMID- 8749580
TI  - Differential effects of aging on memory for content and context: a meta-analysis.
AB  - The authors reviewed the evidence of age differences in episodic memory for
      content of a message and the context associated with it. Specifically, the
      authors tested a hypothesis that memory for context is more vulnerable to aging
      than memory for content. In addition, the authors inquired whether effort at
      encoding and retrieval and type of stimulus material moderate the magnitude of
      age differences in both memory domains. The results of the meta-analysis of 46
      studies confirmed the main hypothesis: Age differences in context memory are
      reliably greater than those in memory for content. Tasks that required greater
      effort during retrieval yielded larger age differences in content but not in
      context memory. The greatest magnitude of age differences in context memory was
      observed for those contextual features that were more likely to have been encoded
      independently from content. Possible mechanisms that may underlie age differences
      in context memory-attentional deficit, reduced working memory capacity, and
      failure of inhibitory processing are discussed.

PMID- 8749581
TI  - Psychological, social, and health impact of caregiving: a comparison of black and
      white dementia family caregivers and noncaregivers.
AB  - Psychological, social, and health variables were compared in 175 Black and White
      family caregivers of patients with dementia and 175 Black and White
      noncaregivers. Caregivers and noncaregivers did not differ within race on
      demographic variables. Caregiving was associated with increased depression and
      decreased life satisfaction only in White families. However, caregiving appears
      to have similar social consequences for Black and White families, including
      restriction of social activity and increased visits and support by family from
      outside of the home. Race, but not caregiving, was associated with physical
      health variables. Methodological issues in comparing well-being in Black and
      White caregivers, in particular the importance of including noncaregiving
      comparison subjects are discussed.

PMID- 8749582
TI  - Stability and accuracy of metamemory in adulthood and aging: a longitudinal
      analysis.
AB  - The stability and accuracy of memory perceptions in 2 longitudinal samples was
      examined. Sample 1 consisted of 231 adults (22-78 years) tested twice over 2
      years. Sample 2 consisted of 234 adults (55-86 years) tested 3 times over 6
      years. Measures of perceived and actual memory change were obtained. A primary
      focus was whether perceptions of memory change stem from application of an
      implicit theory about aging and memory or from accurate monitoring of actual
      changes in performance. Individual differences in metamemory were highly stable
      over time. Results suggested at least some accurate monitoring of memory in
      Sample 2, in which actual change was greatest. However the overall pattern of
      results is largely consistent with predictions derived from an implicit theory
      hypothesis.

PMID- 8749583
TI  - Forgetting in the workplace: attributions and recommendations for young and older
      employees.
AB  - Preceivers assumed the role of manager in a hypothetical company that had either
      high or low bottom-line pressure. Then perceivers made attributions for a young
      or old, male or female, subordinate target employee's memory-related performance
      problems, predictions about future problems, and recommendations about urgency of
      action and type of action necessary. Target age, target gender, and bottom-line
      pressure had no effect on attributions. However, when under high bottom-line
      pressure, perceivers had greater expectation that performance problems would
      continue, felt greater urgency for immediate action, and were less likely to
      recommend training when target employees were old than when they were young.

PMID- 8749584
TI  - Psychological impact of illness downturns: a comparison of new and chronic
      conditions.
AB  - Older adults (N = 166) who had chronic arthritis, a chronic vision problem, new
      arthritis symptoms, or a new vision problem were compared with older adult
      controls on psychological distress and well-being. The psychological impact of
      new versus chronic illness stressors, and stressors associated with arthritis
      versus vision loss, were examined. The chronic arthritis group had the greatest
      psychological distress, the least well-being and the greatest self-reported pain.
      Results supported an additivity theory approach to chronic illness and not an
      anticipatory coping approach. Differences in level of pain accounted in part for
      elevations in distress but did not explain differences between groups in
      psychological well-being. Positive affect was found to be the indicator of well
      being that best differentiated groups.

PMID- 8749585
TI  - Predictors of cognitive change in older persons: MacArthur studies of successful
      aging.
AB  - This study used a linear structural relations modeling technique (LISREL) to
      examine longitudinal data for 1,192 persons from a community-based population.
      The goal was to test the ability of an a priori model to predict cognitive change
      over a 2.0- to 2.5-year period in older adults aged 70-79 at the initial
      evaluation. The model included 22 demographic, physical, and psychosocial
      variables as predictors of cognitive function and cognitive change. The study
      used an exploratory-confirmatory design, enabling cross-validation of the model
      developed in the exploratory set in the confirmatory sample. Structural equation
      modeling analyses identified 4 endogenous model variable (education, strenuous
      activity, peak pulmonary expiratory flow rate, and self-efficacy) as direct
      predictors of cognitive change over the study period.

PMID- 8749586
TI  - Contextual constraint facilitates semantic decisions about object pictures by
      Alzheimer patients.
AB  - Semantic constraints produced by sentence context reduce the time normal adults
      take to decide whether a given stimulus constitutes a meaningful ending to that
      sentence. The mechanism responsible for this constraint effect is thought to
      involve generation of featural restrictions based on context. In the present
      study, participants heard a sentence whose last word was replaced by an object
      picture. They decided whether the object formed a sensible ending to that
      sentence. Contextual constraint present in the sentences greatly influenced
      decision time: the greater the constraint, the faster the decision. Alzheimer
      patients were as affected by contextual constraint as were normal adults. The
      normality of the constraint effect in Alzheimer patients suggests that they can
      generate featural restrictions and thus retain knowledge of the semantic
      attributes of objects.

PMID- 8749587
TI  - Attentional flexibility and aging: you don't need to be 20 years of age to split
      the beam.
AB  - Whether young and old adults were able to selectively attend to noncontiguous
      locations in the visual field and ignore physically interspersed distractor
      stimuli was examined. Participants decided whether 2 letters matched or
      mismatched. Target letter locations were precued by square boxes on an imaginary
      circle centered on fixation. Distractors were located between the 2 targets.
      Young and old were unable to ignore the distractors when the targets and
      distractors were presented as onset stimuli; however both young and old were able
      to ignore the distractors when the target and distractors were presented as non
      onset stimuli. The time course of attentional allocation was equivalent for young
      and old. Results are discussed in terms of models of visual selective attention
      and the flexibility of attentional control.

PMID- 8749588
TI  - Age and health bias in practicing clinical psychologists.
AB  - Although ageism is widely cited as a problem in mental health delivery, it is
      unknown whether practitioner biases are related to factors such as physical
      health. A randomly drawn national sample of experienced practicing doctoral-level
      psychologists (N = 371) responded to detailed vignettes of a client presenting
      with symptoms of depression, in which age (35 years or 70 years) and health
      (unremarkable or poor) were manipulated. Respondents completed ratings involving
      professional and interpersonal judgments about the hypothetical client. Results
      revealed some evidence for age bias, but much stronger effects indicating health
      biases regardless of client age. Because depressed older persons often present
      with concomitant health problems, health bias among clinicians is especially
      relevant for older patients. Implications for service delivery to older adults,
      and individuals with health problems, are discussed.

PMID- 8749589
TI  - Predictors of adherence to a structured exercise program for older women.
AB  - This study examined whether psychological, physiological, and health and
      lifestyle measures were associated with adherence to a structured exercise
      program for older women. Women aged "60 to 85 years (N = 102)," randomly
      recruited from the community, were assessed on these measures before and after a
      12-month exercise trial. Sixty-nine women completed the trial, and 54 continued
      participation after the trial for at least 6 months. Adherence was examined at
      various stages during the trial. Multiple regression analysis revealed that
      reduced muscle strength, slow reaction time, and psychoactive drug use explained
      most of the variance in adherence during the trial. In contrast, muscle strength,
      reasoning ability, depression, and self-reported improvement in strength best
      predicted continued participation after the trial. The findings have implications
      for community-based exercise programs and research trials.

PMID- 8749590
TI  - Depressive symptoms across older spouses and the moderating effect of marital
      closeness.
AB  - Independent interviews with husbands and wives from 317 community-dwelling older
      couples showed that depressive symptoms in 1 spouse had a significant impact on
      depressive symptoms in the other spouse, after controlling for potentially
      confounding respondent sociodemographic and health status variables. Relationship
      quality moderated the influence, with spouse depressive symptoms contributing
      more of the variance to a respondent's symptoms when a couple were close than
      when they were not and closeness to a spouse buffering the potentially depressive
      effects of a respondent's own frailty and financial distress. Husband's own
      variables explained more of the variance in his symptoms when the couple were not
      close than when they were, and closeness to his wife increased a husband's
      vulnerability to the impact of the wife's health status.

PMID- 8749591
TI  - Aging mothers' and their adult daughters' perceptions of conflict behaviors.
AB  - Aging parents tend to perceive greater compatibility between themselves and
      offspring than do off-spring, but there is little research examining differences
      in perceptions of conflicts. Ninety-six older mothers (M age = 76) and their
      daughters (M age = 44) together selected a conflictual incident, then
      individually rated the degree to which they and the other person had engaged in
      destructive, constructive, or avoidant conflict behaviors. Mothers and daughters
      reported using constructive approaches more than other approaches. Mothers
      claimed to engage in constructive behaviors more than daughters recognized.
      Daughters reported engaging in destructive and avoidant behaviors more than
      mothers realized. Mothers also thought daughters felt better about the incident
      than daughters reported feeling about it. Findings suggest older mothers'
      underestimate daughters' negative behaviors and feelings in conflict situations.

PMID- 8749592
TI  - Age-related differences in the detection of three-dimensional surfaces from optic
      flow.
AB  - The present study examined age-related differences in sensitivity to optic flow
      for the detection of 3-D surfaces. Observers were presented with optic flow
      displays simulating either a 3-D corrugated surface or a random velocity pattern
      and were asked to detect the 3-D corrugated surface display. Performance
      decrements were found for older (mean age = 71) compared with younger (mean age =
      21) observers across variations in density and corrugation frequency. Older
      observers also showed performance decrements for a motion coherence task, but
      performance on this task was not significantly correlated with performance on the
      3-D surface detection task. These results suggest that performance on 2-D motion
      tasks is not necessarily predictive of performance on complex 3-D motion tasks.
      In addition, the results suggest that different processes underlie the analysis
      of 2-D and 3-D motion.

PMID- 8749593
TI  - Aging and interference: evidence from indirect memory tests.
AB  - Four experiments examined age differences on indirect memory tests as a function
      of (a) the status of a stimulus as target or distractor and (b) the degree of
      predictability of a stimulus from context. No differences between young and old
      adults were found when targets were clearly designated as such. In this
      situation, participants showed priming for unexpected but not expected stimuli
      whether these words appeared as targets or distractors. In contrast, age
      differences emerged when there was initial uncertainty on each trial as to which
      stimulus was the target. It is concluded that aging is associated with a decrease
      in the efficiency of mechanisms involved in selection.

PMID- 8749594
TI  - Adult age differences in the inhibition of return of visual attention.
AB  - Responses to targets are slower when they appear at a location to which attention
      has previously been directed than when they appear at other locations. This
      inhibition of return (IOR) effect is subserved by posterior brain attentional
      systems. In 4 experiments the IOR effect in elderly adults was found to be at
      least as large as in young adults for both discrimination tasks and for detection
      tasks. The time course and the spread of inhibition within the visual field were
      also equivalent in the 2 age groups. Additive factors logic was then used to test
      the hypothesis that the Stroop and IOR effects are due to a common mechanism, a
      failure to suppress attention. This hypothesis was not confirmed. The results of
      the 6 experiments are consistent with the hypothesis that there are changes in
      posterior brain systems responsible for selective attention to a location,
      contrary to prior claims. They cannot be explained by a general slowing of
      processing in old age.

PMID- 8749595
TI  - Oral contraceptive side effects: where's the beef?
AB  - The initial report is reviewed, as well as the results of subsequent
      investigations, and the current status of the following side effects attributed
      to the use of oral contraceptives: subjective symptoms such as mood and libido
      changes, also headache; melanoma; gallbladder disease; liver tumors, sickle cell
      disease exacerbation; teratogenesis; "post-Pill" amenorrhea; atherogenesis; and
      diminished carbohydrate tolerance. In many instances a cause-and-effect
      relationship appears to be incorrect or highly improbable. In other instances the
      side effects are clinically insignificant or so rare as to be of minimal
      importance. Yet they continue to be listed by various authorities as validated
      side effects or relative contraindications to oral contraceptive use. This, in
      turn, limits the access of many women to a highly effective form of
      contraception. This re-examination of past history is intended to modernize our
      concepts of the safety of this modality.

PMID- 8749596
TI  - Contraception and the risk of ectopic pregnancy: a meta-analysis.
AB  - The current knowledge of the association between contraceptive methods and the
      risk of ectopic pregnancy was evaluated by means of a meta-analysis. Case-control
      and cohort studies published between 1978 and 1994 in English, French, German and
      Dutch were retrieved by a search in Medline, a hand-search on recent medical
      journals and cross-references. Papers reporting on the association between
      contraceptives and ectopic pregnancy were judged according to predefined entrance
      criteria concerning selection of control groups, and retractability of raw data
      enabling the calculation of crude odds ratios. Common Odds Ratios (COR) and 95%
      confidence intervals were calculated if homogeneity was not rejected. Twelve case
      control studies and one cohort study were detected. CORs could be calculated for
      current and past use of oral contraceptives, past IUCD use and tubal
      sterilization. All assessed contraceptives protect against ectopic pregnancy.
      Women becoming pregnant after sterilization or while currently using an IUCD are
      at an increased risk. The IUCD is the only contraceptive method associated with
      an increased risk after discontinuation of its use.

PMID- 8749597
TI  - The influence of Microgynon and Diane-35, two sub-fifty ovulation inhibitors, on
      voice function in women.
AB  - The early days of oral contraceptives showed some evidence that these medications
      may have caused undesirable side effects on the voice, mainly in terms of
      virilization. In a random study carried out at the university hospitals of Jena
      and Berlin (Charite), two more recent drugs were tested in this regard, one
      containing cyproterone acetate (Diane-35) and the other one levonorgestrel
      (Microgynon), both from Schering. Ninety-one patients took part in extensive
      clinical and instrumental phoniatric investigations of voice function over a
      period of one year. No significant side effects on the voice could be proven for
      the two preparations. Gynecological and clinical effects of both Diane-35 and
      Microgynon were similar during the one-year study period. Women taking Diane-35
      had less intracyclic bleedings and amenorrhea. Also, acne was more favorably
      influenced by Diane-35.

PMID- 8749598
TI  - Introduction of Norplant implants in four counties of rural China: a two-year
      evaluation.
AB  - This article describes the first two years of Norplant implants use among 1560
      acceptors in four counties of rural north China. Continuation of use was high,
      88.4% after two years. Disruption of the menstrual cycle was the predominant side
      effect and the predominant reason for termination. Clinical performance among the
      four counties was diverse, with two-year continuation rates ranging from 73.9% to
      95.3%. Factors that may contribute to the diversity among study sites and the
      overall high continuation rate are discussed in the context of Chinese family
      planning.

PMID- 8749599
TI  - Ovarian activity suppression by two different low-dose triphasic oral
      contraceptives.
AB  - In an open, randomized study in an outpatient clinic of a large teaching
      hospital, thirty-one female volunteers with regular cycles and established
      ovulation by ultrasonography were given one of two triphasic oral contraceptives
      containing ethinylestradiol combined with levonorgestrel or desogestrel during
      six cycles of treatment. The main outcome measures were transvaginal
      ultrasonography and serum E2 and P measurements in pill cycles 1, 3 and 6. No
      ovarian activity was found in 10 subjects. Among the remaining 21 women who
      showed ovarian activity, most follicle-like structures developed in the pill-free
      week and decreased in size or disappeared in the first pill week. One women
      taking triphasic desogestrel had evidence of a luteinized unruptured follicle and
      one women taking triphasic levonorgestrel had a possible ovulation. The latter
      women also showed symptoms of lower abdominal pain. A statistically significant
      difference in ovarian activity between the two oral contraceptives could not be
      established. The two triphasic oral contraceptives suppressed ovarian activity to
      the same degree. A trend was seen towards increasing ovarian activity with
      duration of use in both treatment groups.

PMID- 8749600
TI  - The effects of steroidal contraceptives on the well-being and sexuality of women:
      a double-blind, placebo-controlled, two-centre study of combined and progestogen
      only methods.
AB  - A placebo-controlled, double-blind study was carried out to assess the direct
      hormonal effects of combined and progestogen-only oral contraceptives on well
      being and sexuality of women in two contrasting cultures. One-hundred-fifty
      women, who had been sterilised or whose partners had been vasectomised, were
      recruited from two centres-Manila, Philippines, and Edinburgh, Scotland. After
      one month pretreatment assessment, women were randomly assigned to one of three
      treatments (combined oral contraceptive (COC), progestogen-only pill (POP), or
      placebo; 50 within each treatment group, 25 per centre) and continued on
      treatment for four months. Assessment was by daily ratings, questionnaires and
      interviews. The COC adversely affected sexuality in the Edinburgh women, with 12
      of the 25 women in this group also reporting the side effect of reduced sexual
      interest. There were modest negative effects of the combined pill on mood, more
      noticeable in the Edinburgh women. The POP was associated with no adverse effects
      on sexuality and some improvement in well-being in both centres. Possible
      explanations for the apparent lack of adverse effects in the Manila women are
      discussed. The negative effects reported may be less evident in women using the
      COC for contraceptive purposes but may lead to discontinuation in some women and
      warrant further investigation.

PMID- 8749601
TI  - When is it safe to switch from oral contraceptives to hormonal replacement
      therapy?
AB  - Women may continue to use oral contraceptives (OCs) into their 40's and 50's, but
      to date no method has been evaluated to ascertain their ovarian status, i.e.,
      whether fertility and estrogen production have diminished sufficiently so they
      could be safely switched to hormonal replacement therapy. A group of 12
      postmenopausal women who had been, for long periods of time, on a regimen of 3
      back-to-back packages (i.e., 63 days on, 7 days off) of low-dose oral
      contraceptives have been studied. Secondly, a group of 9 perimenopausal women
      aged 36 to 47 were examined in the same manner. The third group consisted of
      early reproductive age women (arbitrarily divided into subsets aged 17-25 and 26
      35 using low-dose OCs in the customary regimen) as normal controls. Blood samples
      were obtained on the last day of a pill cycle and at 7 days off the pill. In some
      menopausal women, blood samples were obtained at both 7 and 14 days off OCs.
      Serum was assayed by RIA for estradiol, FSH and LH. As expected in the young
      reproductive age women, estradiol levels increase at one week off the pill,
      together with a rebound in FSH and LH to follicular phase levels. In the
      perimenopausal group, there was a sharp distinction based on age. The women over
      40 showed a more marked rise in FSH while those aged 36-40 showed a distinctly
      lesser response. Estradiol levels were variable, but tended to show some age
      grouping. Little diagnostic separation was observed for LH. In postmenopausal
      women, FSH levels were not always elevated at one week post-pill, and even in a
      second trial with sampling at one and two weeks off the OC, not all
      postmenopausal women showed a "menopausal" increase in FSH. The more uniform
      feature was that estradiol levels never increased above basal values. The study
      found that serum estradiol levels increase after a week off the pill in controls,
      but are unchanged at one and two weeks in the menopausal group. FSH levels
      rebound normally in reproductive age women and usually, but not always, increase
      substantially in postmenopausal women. After two weeks off OCs, an increased FSH
      and/or no change in basal estradiol levels is strong evidence that it is now safe
      (contraceptively speaking) to switch from OCs to standard hormone replacement
      regimens.

PMID- 8749602
TI  - Orally administered gossypol has no effect on eight hamster erythrocytic enzymes.
AB  - The effectiveness of gossypol as an antifertilizing agent is due to the severe
      injuries or death that this drug produces on spermatozoa and spermatides. Several
      in vitro and in vivo studies have shown that spermatozoal lactic and malic
      dehydrogenases are inhibited by gossypol; and that these are more susceptible
      than the somatic enzymes. Notwithstanding, the in vivo effects on other somatic
      enzymes have been poorly analyzed. The present study shows that gossypol did not
      produce toxic effects on eight erythrocytic enzymes of male hamsters that were
      fed daily with 20 mg of gossypol/kg, for 1, 3, 5 or 10 days. The enzymatic
      activities analyzed were: adenylate kinase, hexokinase, glucose-6-phosphatase,
      glucose phosphoisomerase, phosphofructokinase, glyceraldehyde-3-phosphate
      dehydrogenase, phosphoglyceratokinase and pyruvate kinase.

PMID- 8749603
TI  - Suppression of testicular and epididymal functions in a non-human primate (bonnet
      monkey) by combined administration of a gonadotropin-releasing hormone antagonist
      and testosterone buciclate.
AB  - The ability of a long-acting androgen, testosterone buciclate (TB), to induce
      suppression of testicular and epididymal sperm functions when given in
      combination with a potent GnRH antagonist (Antide) either on day 1 or 45 of
      Antide administration (days 1-90) as well as the ability of TB to maintain Antide
      induced suppression of spermatogenesis were evaluated in adult bonnet monkeys. A
      group of untreated animals (group I) acted as controls. All animals given Antide
      and androgen simultaneously (group II) became azoospermic but at different times.
      When androgen administration was delayed 45 days after start of Antide treatment
      (group III), the mean sperm concentration remained in the normospermic range and
      only three animals became azoospermic. Antide given alone (group IV) induced
      azoospermia in three animals and oligospermia in the remaining animals;
      spermatogenesis recovered when Antide was withdrawn and TB was injected. In all
      Antide-treated animals (groups II-IV), non-motile spermatozoa or sperm with non
      progressive motility and poor gel penetrability were seen in the ejaculate.

PMID- 8749604
TI  - Gossypol-induced apoptotic DNA fragmentation correlates with inhibited protein
      kinase C activity in spermatocytes.
AB  - After exposure of cultured rat spermatocytes to gossypol acetic acid for five
      hours, DNA fragmentation in a ladder pattern was found in the medium and
      supernatants of cell lysates. The concentrations of gossypol used for the
      induction of apoptosis ranged from 100 microM to 300 microM. Within this dose
      range, gossypol was also found to be effective at inhibiting protein kinase C
      (PKC) activity. This inhibitory effect was demonstrated by measuring the PKC
      residing in cytosolic and particulate fractions. However, the gossypol-induced
      inhibition of PKC activity was protected by phorbol 12,13-dibutyrate (PDBu), an
      activator of PKC. Furthermore, the presence of PDBu prevented gossypol-induced
      DNA fragmentation. These results suggest that spermatocyte apoptosis induced by
      gossypol is correlated with the reduction of PKC activity, and that maintenance
      of PKC basal activity is essential for protecting the spermatocyte from
      apoptosis.

PMID- 8749605
TI  - Consensus statement on predictive testing for Alzheimer disease.

PMID- 8749606
TI  - International commentaries on "guidelines for addressing ethical and legal issues
      in Alzheimer disease research".

PMID- 8749607
TI  - Survey of North American and European dementia brain banks: a 1994 directory.

PMID- 8749608
TI  - Autopsy practices at CERAD and Alzheimer disease center sites: a survey of
      neuropathologists.
AB  - A questionnaire, collecting information on methods used at neuropathology core
      facilities for handling of brain autopsies on dementia and control subjects, was
      sent to 29 CERAD (Consortium to Establish a Registry for Alzheimer's Disease)
      and/or Alzheimer's Disease Center (ADC) sites. Neuropathologists shared their
      successes and concerns in response to questions regarding administrative,
      technical, and neuropathological procedures for brain autopsies and tissue
      banking. Adequacy of fiscal support and staff, scarcity of control cases, and
      logistical aspects of autopsy coordination emerged as common problems. Successful
      strategies included the designation of dedicated autopsy coordinators, enhanced
      relationships with community hospital pathologists and funeral homes, and
      increased multilevel educational efforts on the importance of the autopsy.

PMID- 8749609
TI  - Clinicopathologic study of probable Alzheimer disease: assessment of criteria for
      excluding cerebrovascular disease.
AB  - The National Institute of Neurological and Communicative Disorders and
      Stroke/Alzheimer Disease and Related Disorders Association criteria for probable
      Alzheimer disease (AD) require exclusion of non-AD dementia-producing conditions
      but do not specify how the non-AD conditions are to be identified. We addressed
      this issue for the case of cerebrovascular disease (CVD) by defining exclusion
      rules based on commonly described clinical features: (a) history of strokelike
      episodes; (b) history of stepwise cognitive decline; (c) focal deficits on
      neurological examination; and (d) evidence of significant CVD on neuroimaging. We
      applied these rules retrospectively to clinical records for 92 cognitively
      impaired patients who otherwise met criteria for probable AD and whose brains
      were subsequently available for postmortem examination. We used Fisher's exact
      test to assess the effectiveness of the exclusion rules in predicting the
      presence of CVD on autopsy. Prediction was better than chance when all four
      clinical features were used together (p = 0.0008) and when the stepwise decline
      or neuroimaging criteria were used alone (p = 0.03 and p = 0.05, respectively).
      Overall, the CVD exclusion rules were deficient because of low accuracy (50.0%)
      and low sensitivity (52.6%). These results support provisional use of the CVD
      criteria chosen for this study but suggest that modifications are needed for
      acceptable diagnostic accuracy and sensitivity to be achieved.

PMID- 8749610
TI  - Reduction of platelet phospholipase C activity in patients with Alzheimer
      disease.
AB  - Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal
      transduction. We have previously demonstrated that a PLC isozyme is abnormally
      accumulated in the brain tissue in Alzheimer's disease (AD). AD has been
      suggested to be a systemic disease in which the expression of abnormalities is
      most prominent in neuronal tissues. In a recent study, we have revealed the
      increase of the cytosolic protein kinase C (PKC) concentration in platelets of AD
      patients, suggesting the change of PLC, which is upstream to PKC in
      phosphoinositide metabolism. In this study, we examined phosphatidylinositol
      specific PLC activity in platelets from patients with AD and age-matched controls
      by measuring the formation of radioactive inositol phosphate. The PLC activity
      was significantly lower in the AD platelets than in the controls. These findings
      suggest that aberrant phosphoinositide metabolism is present in nonneuronal
      tissues as well as the brain in AD.

PMID- 8749611
TI  - Abnormally phosphorylated tau protein in senile dementia of Lewy body type and
      Alzheimer disease: evidence that the disorders are distinct.
AB  - The relationship between Alzheimer disease (AD) and dementia with Lewy bodies
      (senile dementia Lewy body type, or SDLT) and dementia in Parkinson's disease is
      unclear. AD pathology is characterised by both amyloid deposition and abnormal
      phosphorylation of tau in paired helical filaments (PHF-tau). In AD, abnormally
      phosphorylated PHF-tau is present in neurofibrillary tangles, in neuritic
      processes of senile plaques, and also in neuropil threads dispersed throughout
      the cerebral cortex. Cortical homogenates from 12 cases each of AD and SDLT, 13
      cases of Parkinson's disease, and 11 normal controls were examined by Western
      blot analysis with antibodies that detect PHF-tau. No PHF-tau was found in
      Parkinson's disease or control cortex. No PHF-tau was found in SDLT cases without
      histological evidence of tangles. PHF-tau was detectable in SDLT cases with a low
      density of tangles, and large amounts of PHF-tau were present in AD cases. This
      study demonstrates that abnormally phosphorylated PHF-tau is only present where
      tangles are found and not in SDLT cases without tangles or with only occasional
      tangles. It is concluded that Lewy body dementias are distinct at a molecular
      level from AD.

PMID- 8749612
TI  - Treatment of Alzheimer disease by continuous intravenous infusion of
      physostigmine.
AB  - Physostigmine, a reversible and nonselective cholinesterase inhibitor,
      administered by steady-state, continuous intravenous infusion to carefully
      selected subjects with mild-moderate Alzheimer disease, produced significant but
      modest improvement in memory in five of nine subjects. Drug dosing was limited by
      the occurrence of adverse effects. Apparent tolerance to adverse effects was
      observed in two subjects when the dose of physostigmine was escalated slowly over
      at least 2 weeks. Steady-state cholinesterase inhibition by physostigmine appears
      to produce sustained cognitive improvement in some subjects with Alzheimer
      disease without substantially altering its therapeutic index.

PMID- 8749613
TI  - Low-dose propranolol reduces aggression and agitation resembling that associated
      with orbitofrontal dysfunction in elderly demented patients.
AB  - Although several reports suggest that intermediate to high doses of propranolol
      (80-160 and 200-600 mg/day) can effectively treat aggressive behavior in
      dementia, significant side effects can occur at these doses. To minimize these
      side effects, we treated and followed-up a series of 12 demented patients, whose
      caregivers sought medical help for their disruptive, aggressive behavior, with
      low-dose propranolol monotherapy (10-80 mg/day). Assessment measures obtained at
      baseline and during treatment by caregiver interview included ordinal ratings of
      aggression severity, the Cohen-Mansfield Agitation Inventory (CMAI), and the
      California Behavior Questionnaire (CBQ). The aggression ratings showed that low
      dose propranolol effectively reduced aggression in eight of 12 patients (67%)
      within 2 weeks of treatment and remained effective for the duration of follow-up
      (1 to 14 months). Subscales of the CMAI showed responders to have significant
      reductions in physical and verbal aggression/agitation and in pacing/wandering.
      These results suggest that low-dose propranolol should be further studied for
      treating aggression or agitation in demented patients.

PMID- 8749614
TI  - Plasma arginine vasopressin response to hypertonic saline infusion in Alzheimer
      disease.
AB  - In this study, we tested the hypothesis that the plasma arginine vasopressin
      (AVP) response to osmotic stimulation induced by hypertonic saline infusion is
      blunted in the early and middle stages of Alzheimer disease (AD). Because animal
      data support stimulatory cholinergic mediation of AVP osmoregulation at a brain
      level, the AVP response in AD might provide clinically useful information about
      the status of brain cholinergic systems. Seventeen AD outpatients and eight
      normal older subjects underwent both a 90-min hypertonic saline infusion and a 90
      min control (normal saline) infusion. Substantial increases in plasma osmolality
      during hypertonic saline infusion were accompanied by substantial and linear
      increases in plasma AVP in both groups. However, there were no significant
      differences in AVP responses between AD and normal older subjects. These results
      do not support the utility of plasma AVP response to hypertonic saline in the
      assessment of brain cholinergic status in AD.

PMID- 8749615
TI  - Orthostasis in Alzheimer disease: a retrospective analysis.
AB  - Vitiello et al. (1993) recently reported statistically significant decreases in
      systolic blood pressure upon standing in patients with Alzheimer disease (AD) (n
      = 60) as compared with healthy elderly controls (n = 20), which would suggest a
      possible autonomic dysfunction associated with AD. To investigate this issue, we
      conducted a retrospective analysis of blood pressures and heart rates of 31
      patients 55-85 years of age (mean 69.6) who met National Institute of
      Neurological and Communicative Disorders and Stroke/Alzheimer Disease and Related
      Disorders Association criteria for probable AD. The patients were selected from a
      pool of placebo-treated patients with AD in five inpatient phase I clinical
      trials. All patients met rigorous entrance criteria and thus were in excellent
      physical health except for AD. Blood pressure and pulse were assessed after 3-5
      min of lying down and after 1-3 min of standing. Systolic and diastolic blood
      pressures showed decreases upon standing of 12 mm Hg (8.6%) and 6 mm Hg (8.2%),
      respectively, on day 1 and decreases of 10 mm Hg (7.6%) and 4 mm Hg (5.7%),
      respectively, on day 7 of hospitalization (p < 0.05). Pulse rates increased upon
      standing by 17% and 13% on days 1 and 7, respectively (p < 0.05). Our data
      support the finding of Vitiello et al. of significant postural decreases in
      systolic blood pressure in patients with AD. Well-controlled, prospective studies
      of orthostasis in AD and healthy elderly subjects should be conducted to
      determine its prevalence in both populations and to determine whether the
      orthostatic changes seen in AD differ from those in normal aging.

PMID- 8749616
TI  - Syphilis in adults: from Christopher Columbus to Sir Alexander Fleming to AIDS.

PMID- 8749617
TI  - Diagnosis and treatment of hepatic hydatid cysts with the aid of echo-guided
      percutaneous cyst puncture.
AB  - The usefulness of echo-guided percutaneous cyst puncture in the diagnosis and
      treatment of hepatic hydatid cysts was assessed in a study of 45 patients
      referred to the Department of Tropical Medicine at Kasr El Aini Hospital in
      Cairo. All subjects had at least one hepatic cyst detected by ultrasonography (54
      cysts in all), and 42 patients had positive results in serological tests for
      antibodies to Echinococcus granulosus. The majority of cysts were in the right
      hepatic lobe (40 cysts), were anechoic (51), and were rounded and smooth (49).
      All 45 active cysts (44 anechoic, rounded, and smooth; one anechoic and septated)
      yielded clear watery fluid containing scolices and exhibited elevated pressure on
      percutaneous puncture. In contrast, all nine inactive cysts yielded cloudy
      yellowish fluid without detectable scolices and did not display elevated pressure
      on puncture. The latter cysts were anechoic and elliptical (two cysts); anechoic
      and septated (one); anechoic with a calcified wall (one) or a detached germinal
      layer (two); or rounded with coarse echoes (three). Treatment by injection of a
      scolicidal agent (hypertonic saline) before withdrawal of the needle used for
      aspiration gave excellent results and was not associated with complications.
      Forty-three of the 45 patients had no clinical or ultrasonographic evidence of
      recurrent or new hepatic cysts after 3 years of follow-up.

PMID- 8749618
TI  - Photo quiz.

PMID- 8749619
TI  - Outpatient use of erythromycin: link to increased erythromycin resistance in
      group A streptococci.
AB  - Resistance to erythromycin in group A streptococci has become an important
      problem among outpatients in Finland. The prevention of such problems requires
      information about the relationship between antimicrobial consumption and
      antimicrobial resistance. Having found considerable variation among health
      authority areas in the proportions of group A streptococci resistant to
      erythromycin, we investigated the potential impact of local differences in the
      consumption of this agent on the development of resistance. In 1992, 10,162 group
      A streptococcal isolates (nearly 100% were from outpatients) collected from 206
      health authority areas were tested for erythromycin resistance; 1,647 isolates
      (16%) were resistant. Logistic regression analysis showed that the proportion of
      isolates resistant to erythromycin clearly increased with increasing local
      erythromycin consumption by outpatients in 1991 (P = .006). This positive
      association indicates that a prudent policy for the treatment of outpatients is
      essential to maintenance of the effectiveness of antimicrobial agents.

PMID- 8749620
TI  - Seroepidemiology of chronic fatigue syndrome: a case-control study.
AB  - We performed serological testing for a large number of infectious agents in 26
      patients from Atlanta who had chronic fatigue syndrome (CFS) and in 50 controls
      matched by age, race, and sex. We did not find any agent associated with CFS. In
      addition, we did not find elevated levels of antibody to any of a wide range of
      agents examined. In particular, we did not find elevated titers of antibody to
      any herpesvirus, nor did we find evidence of enteroviral exposure in this group
      of patients.

PMID- 8749621
TI  - Pneumococcal meningitis in children: prognostic indicators and outcome.
AB  - We studied the outcome of pneumococcal meningitis in 83 children who were
      admitted to a referral hospital and whose meningitis was diagnosed between 1970
      and 1994. The median age of the children was 8 months. The most frequently
      isolated capsular serotypes and/or serogroups of Streptococcus pneumoniae were 6,
      14, 18, 19, and 23. Twenty-nine children (35%) were referred by other hospitals.
      A mortality rate of 17% (primary referrals, 7%; secondary referrals, 35%) was
      observed. At discharge, 25 survivors (36%) had sequelae: hearing loss (> or = 30
      dB) in 19% and neurological sequelae in 25%. During admission, the presence of
      coma, respiratory distress, shock, a cerebrospinal fluid (CSF) protein level of >
      or = 2.5 g/L, a peripheral white blood cell count of < 5 x 10(9)/L, and a serum
      sodium level of < 135 mmol/L were associated with mortality. Sequelae were
      associated with the presence of coma and a CSF glucose level of < 0.6 mmol/L. We
      conclude that the mortality rate of pneumococcal meningitis is lower among
      children than among adults. Children often die of neurological sequelae, while
      adults frequently die of cardiorespiratory failure due to underlying diseases.
      For children, coma, respiratory distress, and shock during admission were the
      clinical findings with the strongest predictive value for sequelae or death.

PMID- 8749622
TI  - Antimicrobial resistance and type distribution of Streptococcus pneumoniae
      isolates causing systemic infections in Germany, 1992-1994.
AB  - A prospective study of pneumococcal infections was performed in cooperation with
      40 clinical microbiology laboratories in Germany. Minimal inhibitory
      concentration (MIC) values for 844 strains of Streptococcus pneumoniae, isolated
      from patients with systemic infections, were determined in tests with penicillin,
      tetracycline, erythromycin, chloramphenicol, cefotaxime, and clindamycin by a
      standard broth microdilution method; 1.8% of pneumococcal isolates exhibited
      reduced susceptibility to penicillin (MIC, > or = 0.1 micrograms/mL). The Etest,
      which was used to confirm the level of resistance to penicillin, proved to be a
      reliable and easily performed method for determination of MICs. The rates of
      resistance to clindamycin, erythromycin, tetracycline, and chloramphenicol were
      1.4%, 3.2%, 11.0%, and 1.9%, respectively. Resistance to cefotaxime was not
      observed. Typing of a randomly selected subgroup of all strains (n = 115) showed
      types 1 (9.6%), 14 (8.7%), 3 (7.8%), and 23F (7.8%) to be the most prevalent
      types in Germany. At least 86.1% of these pneumococcal strains belonged to
      capsular types included in the 23-valent vaccine.

PMID- 8749623
TI  - Bacterial vaginosis in lesbians: a sexually transmitted disease.
AB  - Sexual transmission of bacterial vaginosis (BV), a common syndrome in sexually
      active women, has not been previously established. Because no male counterpart
      for BV has been found, a population of lesbians is an ideal one in which to test
      the hypothesis that BV is sexually transmitted. We studied 103 homosexual women
      (lesbians) who sought gynecologic care at a community clinic and in a private
      gynecology practice in New York City. Participants were asked to refer their
      sexual partners for evaluation. In this cross-sectional prevalence study, all
      participants were evaluated for the presence of BV, and pairs of monogamous
      sexual partners were analyzed for concordance of their vaginal secretions. Twenty
      nine (28.7%) of the 101 participants from whom satisfactory vaginal wash samples
      were available had BV. There were 21 pairs of monogamous partners. Of 11 index
      women who had BV, eight (72.7%) had partners who also had BV. Of 10 index women
      who did not have BV, only one (10%) had a partner with BV. The likelihood of a
      partner's having BV was 19.7 times greater if the index case had BV (P < .008;
      95% CI, 2.1-588.0). We conclude that with respect to BV, lesbians in monogamous
      relationships usually have concordant vaginal secretions. This concordance
      probably reflects the sexual transmission of BV between lesbians.

PMID- 8749624
TI  - Treatment of streptococcal endocarditis with a single daily dose of ceftriaxone
      and netilmicin for 14 days: a prospective multicenter study.
AB  - A 2-week course of ceftriaxone (2 g) plus netilmicin (4 mg/kg), administered as
      one short daily iv infusion, was evaluated for the treatment of streptococcal
      endocarditis in an open multicenter study. Of the 52 patients, 31 were infected
      with viridans streptococci, 18 with Streptococcus bovis, two with Gemella
      morbillorum, and one with group C Streptococcus; 48 patients were assessable.
      Infection was cured in 42 cases, 35 treated medically and seven treated both
      medically and surgically. Five patients died without evidence of active
      infection, and one relapsed. The bacteriologic failure was due to a strain of G.
      morbillorum against which no synergy of ceftriaxone and netilmicin was evident in
      vitro. The serum creatinine level increased during treatment in four cases, all
      involving patients > 65 years old who had renal risk factors; in two of these
      cases, values did not return to baseline during follow-up. Of 40 patients
      assessed for auditory function, only one developed decreased perception of
      borderline significance. Other adverse reactions were mild. This regimen was
      efficacious, safe, and cost-effective for the treatment of streptococcal
      endocarditis. However, it must be used with caution for patients with preexisting
      renal impairment or concomitant exposure to other potentially nephrotoxic agents.

PMID- 8749625
TI  - Application of neural networks to the real-time diagnosis of acute toxoplasmic
      infection in immunocompetent patients.
AB  - Neural networks constitute a relatively new, radically different approach to the
      interpretation and recognition of subtle diagnostic patterns in multivariate
      data. In this study the use of neural networks with a single serum sample for
      rapid real-time recognition of recent toxoplasmic infection was investigated. A
      neural-network model was implemented on the basis of data obtained by four
      serological methods--dye test, indirect fluorescence assay, indirect
      hemagglutination assay, and IgM immunosorbent agglutination assay--and was
      "trained" to extract features of acute infection by application to an analysis of
      65 immunocompetent patients, 10 of whom were in fact acutely infected. The
      trained model correctly classified all 10 cases of acute infection. On its
      application to 61 additional infected patients, this method correctly identified
      seven cases as potentially acute. Our study shows that neural networks can
      discern diagnostic patterns from variables that individually have limited utility
      in the diagnosis of acute toxoplasmosis.

PMID- 8749626
TI  - Mortality associated with nosocomial bacteremia due to methicillin-resistant
      Staphylococcus aureus.
AB  - We prospectively studied all cases of Staphylococcus aureus bacteremia that
      occurred during an extensive outbreak of methicillin-resistant S. aureus (MRSA)
      in our hospital over a 4-year period (January 1990 through September 1993). We
      report the results of a comparative analysis of the clinical characteristics and
      mortality rates among patients with nosocomial bacteremia caused by MRSA (84
      cases) or methicillin-susceptible S. aureus (MSSA; 100 cases). The patients with
      MRSA bacteremia were older than those with MSSA bacteremia (69 years vs. 54
      years, respectively; P < .01) and were more likely than those with MSSA
      bacteremia to have the following predisposing factors: a prolonged
      hospitalization (32 days vs. 14 days, respectively; P < .01); prior antimicrobial
      therapy (61% vs. 34%, respectively; P < .01); urinary catheterization (58% vs.
      27%, respectively; P < .01); nasogastric tube placement (31% vs. 13%,
      respectively; P < .01); and prior surgery (45% vs. 31%, respectively; P = .05).
      Multivariate analysis with use of the stepwise logistic regression method showed
      a relationship between mortality and the following variables: methicillin
      resistance (odds ratio [OR], 3), meningitis (OR, 13), and inadequate treatment
      (OR, 11).

PMID- 8749627
TI  - Spectrum of parvovirus B19 infection: analysis of an outbreak of 43 cases in
      Cadiz, Spain.
AB  - In the spring of 1993, an epidemic of infection with human parvovirus B19
      occurred in Cadiz, Spain. Evaluation of the 43 patients in whom this diagnosis
      was confirmed revealed four groups of predominant manifestations: (1) hematologic
      manifestations in six cases (13.9%), including four of aplastic crisis and two of
      pancytopenia; (2) dermatologic manifestations in 23 cases (53.4%), including 10
      of erythema infectiosum and one of erythema multiforme ampullosum; (3)
      arthralgias/arthritis in nine cases (20.9%), including two with a chronic course;
      and (4) infection during pregnancy in three cases (7.0%), including two that
      ended in abortion. Of the 43 patients, 37.2% presented with fever and
      adenopathies, and these were the only manifestations in two cases. The appearance
      of clinical disease correlated with modifications in isotype and serum level of
      specific antibodies to parvovirus B19; the disappearance of IgM antibodies
      coincided with the resolution of clinical manifestations. Although their presence
      did not correlate with the course of the disease, the detection of circulating
      immune complexes in 81.6% of cases supports the possibility that some
      manifestations were immune mediated.

PMID- 8749628
TI  - Alterations in gastric acidity in patients infected with human immunodeficiency
      virus.
AB  - In a randomized crossover trial, gastric acidity and gastric microbial
      colonization in 19 men infected with human immunodeficiency virus (HIV) (of whom
      nine had AIDS) were assessed. Gastric acidity was assessed during a baseline
      period and following pentagastrin or glutamic acid administration. Only two
      (22.2%) of the nine patients with AIDS and none of the non-AIDS patients were
      hypochlorhydric, as determined by maximal acid output. However, 60% and 67% of
      patients in the HIV-infected and AIDS groups, respectively, had persistently
      elevated gastric pH values during the baseline period. Both pentagastrin and
      glutamic acid significantly increased gastric acidity. Gastric colonization with
      Candida albicans and gram-positive mouth flora was common. Overall, this study
      demonstrates that many HIV-infected patients have elevated gastric pH values that
      may lead to alteration in drug absorption. The large degree of intrasubject and
      intersubject variability observed in gastric pH suggests that, unfortunately, one
      cannot predict which patients will have elevated gastric pH values.

PMID- 8749629
TI  - Present status of the use of cytokines as adjuvants with vaccines to protect
      against infectious diseases.
AB  - Vaccine adjuvants are expected to play an important role in enhancing the
      immunogenicity of existing and new-generation vaccines against infectious
      diseases. In particular, adjuvants should direct the immune response in the most
      appropriate manner--furthering, for example, an expanded B-cell response, a
      cytotoxic T-cell response, or a T-helper 1 or 2 subset response. While some
      noncytokine adjuvants have exerted potent effects, their modes of action are most
      likely mediated by cytokines. Several cytokines have already been shown to be
      efficient adjuvants in animal models and/or in clinical trials. The mechanisms of
      cytokine function must be better understood and the techniques for the use of
      cytokines improved if the full potential of these substances as vaccine adjuvants
      is to be realized. When used to best advantage, such adjuvants enhance the
      immunity induced by viral, bacterial, and parasitic vaccines and thereby promote
      efficient protection or even cure.

PMID- 8749630
TI  - Management of vaginal discharge in women treated at a Jamaican sexually
      transmitted disease clinic: use of diagnostic algorithms versus laboratory
      testing.
AB  - The management of cervical infections is difficult in developing countries
      because laboratory facilities for diagnosing these infections are seldom
      available; therefore, syndrome-based management has been recommended by the World
      Health Organization (WHO). However, such alternative approaches need to be
      evaluated in real field settings. We used algorithms (flowcharts) for syndromic
      management of abnormal vaginal discharge to treat 752 women who presented at a
      Jamaican sexually transmitted disease (STD) clinic. Laboratory testing revealed
      cervical infection (gonococcal and/or chlamydial) in 34% of these women;
      trichomoniasis was documented for 25%; and at least one STD was documented for
      54% of the women. Use of a clinical algorithm for diagnosing cervical infection
      was 73% sensitive (95% CI, 67-78) and 55% specific (95% CI, 49-62) when compared
      with laboratory testing. The risk-assessment-inclusive flowchart developed by WHO
      was 84% sensitive (95% CI, 80-89) and 40% specific (95% CI, 34-46) for diagnosing
      cervical infection. Positive predictive values for diagnosing cervical infection
      with use of the algorithms ranged from 42% to 43%, and negative predictive values
      ranged from 78% to 81%. The sensitivity of the algorithms for diagnosing
      trichomoniasis ranged from 85% to 88%. To treat as many infected women as
      possible, the most sensitive algorithm was selected for routine use in Jamaican
      STD clinics.

PMID- 8749631
TI  - Editorial: how should clinical algorithms be used for syndromic management of
      cervical and vaginal infections?

PMID- 8749632
TI  - Lactobacillemia in three patients with AIDS.
AB  - Lactobacillemia, an uncommon cause of bacteremia, has been reported to occur in
      one renal transplantation patient who was also infected with human
      immunodeficiency virus (HIV). We present the cases of three patients with AIDS in
      whom lactobacillemia developed. All three patients had late-stage AIDS with CD4
      cell counts of < 55/mm3, all had indwelling central venous catheters, and all
      were recently or concomitantly blood culture-positive for coagulase-negative
      staphylococci. In addition, two of the three patients had recently received
      vancomycin therapy. These three cases provide the first association of
      lactobacillus bacteremia and AIDS.

PMID- 8749633
TI  - Reactive hemophagocytic syndrome: a new presentation of disseminated
      histoplasmosis in patients with AIDS.
AB  - We report the cases of six patients with AIDS in whom reactive hemophagocytic
      syndrome (RHPS) secondary to disseminated histoplasmosis was diagnosed. RHPS was
      diagnosed by established criteria, including fever (duration of > or = 7 days,
      with peak temperatures of > 38.5 degrees C), unexplained thrombocytopenia with
      anemia and/or neutropenia, and bone marrow biopsy findings of hemophagocytic
      histiocytosis. Disseminated Histoplasma capsulatum infection was diagnosed on the
      basis of the results of cultures of the bone marrow sample. The serum lactate
      dehydrogenase (LDH) level was elevated (> 1,000 IU/L) in all patients, and five
      of six patients had hyperferritinemia (range of ferritin level, 15,848-425,984
      ng/mL). Five patients had features resembling severe sepsis with multiorgan
      dysfunction. Three patients recovered, and the findings of RHPS resolved
      following therapy with amphotericin B. In patients with AIDS, the combination of
      fever, cytopenia, elevated serum LDH level (> 1,000 IU/L), and/or
      hyperferritinemia (ferritin level of > 10,000 ng/mL) is a clue to the diagnosis
      of RHPS and disseminated histoplasmosis; bone marrow biopsy is valuable in
      establishing the diagnosis.

PMID- 8749634
TI  - Immunodeficiency and elevated CD4 T lymphocyte counts in two patients coinfected
      with human immunodeficiency virus and human lymphotropic virus type I.
AB  - We describe two patients who were coinfected with human immunodeficiency virus
      (HIV) and human T-cell lymphotropic virus (HTLV) type I. They had clinical
      evidence of immunodeficiency (anergy, oral candidiasis, and disseminated herpes
      zoster) despite having elevated CD4 T lymphocyte counts (range, 2,450-5,292/mm3).
      We conclude that CD4 lymphocyte counts may not be reliable markers of immunologic
      competence in patients coinfected with HIV and HTLV-I.

PMID- 8749635
TI  - Clinical usefulness of intravenous human immunoglobulins in invasive group A
      Streptococcal infections: case report and review.
AB  - The spectrum of invasive Streptococcus pyogenes (group A streptococcus)
      infections includes bacteremia, toxic shock syndrome, and necrotizing fasciitis
      or myositis. We report the successful use of intravenous immunoglobulins in
      conjunction with antibiotics and surgery in a case of necrotizing myositis, toxic
      shock, and bacteremia. A literature review revealed that three other patients
      with invasive group A streptococcal infections had been treated with
      immunoglobulins: one adult patient had toxic shock syndrome, one had necrotizing
      fasciitis, and one child had septic arthritis. On the basis of this report and
      the review, we suggest that intravenous immunoglobulins may be useful in the
      treatment of all forms of invasive group A streptococcal infections associated
      with toxic shock syndrome.

PMID- 8749636
TI  - Childhood bacterial meningitis in Southwestern Greece: a population-based study.
AB  - During the 5-year period from 1990 through 1994, we investigated the incidence of
      childhood bacterial meningitis (beyond the neonatal period) in southwestern
      Greece. Thirty-seven cases of bacterial meningitis were identified. Fifty-one
      percent of the cases were caused by Neisseria meningitidis, 41% by Haemophilus
      influenzae type b (Hib), and 8% by Streptococcus pneumoniae. Fifty-eight percent
      and 73% of cases of meningococcal and Hib meningitis, respectively, involved
      children younger than 2 years of age. The average yearly incidences of
      meningococcal and Hib meningitis were 9.7 and 8 cases, respectively, per 100,000
      children < 5 years of age. The main difference between findings in this study and
      those in other studies in Western European countries is the lower incidence of
      Hib meningitis observed in our area. This low incidence of Hib meningitis cannot
      be attributed to the use of vaccine because the Hib vaccine was first introduced
      in May 1994 and used infrequently through December 1994.

PMID- 8749637
TI  - Vertebral osteomyelitis due to Roseomonas species: case report and review of the
      evaluation of vertebral osteomyelitis.
AB  - We report what we believe is the first case of vertebral osteomyelitis caused by
      Roseomonas species. The diagnosis of vertebral osteomyelitis can be difficult.
      The case illustrates the importance of the establishment of an etiologic
      diagnosis in vertebral osteomyelitis. The features of Roseomonas species and the
      evaluation of cases of vertebral osteomyelitis are reviewed.

PMID- 8749638
TI  - Serum therapy for Cryptococcal meningitis.
AB  - Three patients were treated with combined amphotericin B and rabbit
      anticryptococcal antibody in the 1960s. Rabbit antibody was administered
      intravenously and was well tolerated. For each patient, administration of rabbit
      antibody resulted in the appearance of serum Cryptococcus neoformans agglutinins.
      For two patients the administration of rabbit antibody resulted in negative serum
      latex tests for cryptococcal antigen. This limited experience with adjunctive
      antibody therapy provides valuable precedents if antibody therapy is used again
      for treatment of human cryptococcosis.

PMID- 8749639
TI  - Immunologically confirmed disseminated, asymptomatic Encephalitozoon cuniculi
      infection of the gastrointestinal tract in a patient with AIDS.
AB  - Microsporidia are obligate intracellular protozoan parasites that infect a broad
      range of vertebrates and invertebrates. They are increasingly recognized as human
      pathogens, especially in patients infected with human immunodeficiency virus
      (HIV). Organisms of the genus Encephalitozoon have been implicated as a major
      cause of disseminated microsporidian infections in persons with AIDS. Until
      recently, E. hellem was the only Encephalitozoon species confirmed by antigenic
      or nucleic acid methods to have infected humans. We describe the clinical course
      and morphological features of a case of disseminated microsporidian infection
      with Encephalitozoon cuniculi in an HIV-infected patient with chronic sinusitis,
      rhinitis, and keratoconjunctivitis. Parasites were found in conjunctival swab,
      nasal discharge, sputum, urine, stool, and duodenal biopsy specimens, but no
      pulmonary, renal, or gastrointestinal symptoms were documented. The patient was
      treated with albendazole (400 mg po b.i.d.), resulting in complete remission of
      his ocular and nasal symptoms, and microsporidian spores disappeared from all
      sites. To our knowledge, this case is only the second of E. cuniculi infection in
      humans that has been confirmed by either antibody- or nucleic acid-based methods,
      and it is the first in which an Encephalitozoon species has been found in the
      intestinal tract of a human. Microsporidiosis is an important emerging
      opportunistic infection in HIV-infected patients and, as documented in this
      report, has an expanding clinicopathologic spectrum.

PMID- 8749640
TI  - Treatment of cerebral Aspergillosis with itraconazole: do high doses improve the
      prognosis?
AB  - We describe a 72-year-old woman with chronic asthma who presented with cerebral
      abscesses due to Aspergillus fumigatus after she received treatment with
      corticosteroids. Therapy with high-dose itraconazole (800 mg/d for 5 months,
      followed by 400 mg/d for an additional 4.5 months) resulted in complete
      resolution of all lesions. Serum concentrations of the drug ranged from 2
      micrograms/mL to 30 micrograms/mL. Review of 20 cases of cerebral aspergillosis
      that were treated with itraconazole revealed that three of the four patients who
      received high doses (800 mg/d in the adults) of the drug responded favorably,
      while only two of the 16 patients who received a dose of 400 mg/d were cured. The
      use of high-dose itraconazole appears to be justified for high-risk patients with
      cerebral aspergillosis for whom conventional therapy has failed.

PMID- 8749641
TI  - Hemorrhagic stroke as a complication of bacterial meningitis in adults: report of
      three cases and review.
AB  - We describe three adults who had hemorrhagic strokes during the acute phase of
      bacterial meningitis (BM). We also report the results of a literature review and
      a review of the charts of 296 adults treated at our hospital for acute BM. The
      diagnosis of hemorrhagic stroke was made based on the results of cerebral
      computed tomography (CT) for two of 92 patients with BM who had CT performed and
      by means of lumbar puncture and a postmortem study in one other case. Two
      patients died of cerebral bleeding. Although the frequency of hemorrhagic stroke
      was only 2.1% among adults with acute BM, it is a major determinant of prognosis
      for such patients.

PMID- 8749642
TI  - Inflammatory pseudotumor presenting as fever of unknown origin.
AB  - Inflammatory pseudotumor (IPT) is an uncommon benign neoplasm of uncertain
      etiology that classically has been associated with the lung, where it is
      generally asymptomatic. In recent years, IPT has been increasingly recognized in
      other sites. Hepatic, abdominal, and pelvic IPTs produce a spectrum of
      nonspecific symptoms including fever, malaise, anemia, and weight loss. Because
      prolonged fever is a prominent feature of extrapulmonary IPT, patients with this
      condition may first come to the attention of specialists in infectious diseases.
      We describe an illustrative case of pelvic IPT and discuss its presentation,
      diagnosis, and treatment; we also suggest that infectious disease specialists
      should be familiar with this entity as a possible diagnosis for patients with
      fever of unknown origin.

PMID- 8749643
TI  - Diagnosis of ornithosis by cell culture and polymerase chain reaction in a
      patient with chronic pneumonia.
AB  - We report the case of a woman who had pneumonia due to Chlamydia psittaci. A
      Chlamydia species was determined to be the causative agent of the pneumonia
      because it was isolated from bronchoalveolar lavage fluid, because it could be
      detected in lung biopsy specimens by the direct immunofluorescence technique, and
      because Chlamydia-specific antibodies could be detected by ELISA and
      microimmunofluorescence. The infectious agent could not be identified at the
      species level with use of serological techniques, but the isolate was determined
      to be C. psittaci by PCR with use of species- and genus-specific sequences within
      the chlamydial lipopolysaccharide biosynthesis gene gseA. The case reported
      herein exemplifies the problems encountered in diagnosing ornithosis and shows
      that isolation of the etiologic agent followed by identification of the species
      by PCR is helpful in diagnosing this rare disease. In addition, the findings in
      our case show that laboratory personnel who are conducting tests for Chlamydia
      pneumoniae should be aware of the risk of accidentally isolating highly
      infectious C. psittaci organisms.

PMID- 8749644
TI  - Prognostic significance of quantitative bacteremia in septicemic melioidosis.
AB  - Pour-plate blood cultures were performed for 418 adult patients with suspected
      septicemic melioidosis in order to determine the relationship between
      quantitative bacterial counts in blood and mortality. Of 108 patients whose
      hemocultures yielded Burkholderia pseudomallei, 53% had < 10 cfu/mL and 24% had >
      100 cfu/mL. High blood bacterial counts were more common than reported previously
      with regard to other gram-negative septicemias and were significantly associated
      with the development of hypotension (P = .008) and a fatal outcome (P = .0001).
      The overall mortality was 63% (95% CI, 53%-72%); however, counts of < or = 1
      cfu/mL were associated with a mortality of 42% (95% CI, 28%-58%), compared with
      96% (95% CI, 80%-100%) with counts of > 100 cfu/mL. Heavy bacteremia (> 50
      cfu/mL) is common in septicemic melioidosis and is usually fatal.

PMID- 8749645
TI  - An outbreak of infusion-related Klebsiella pneumoniae bacteremia in a liver
      transplantation unit.
AB  - Over a 1-month period, there were five episodes of infusion-related Klebsiella
      pneumoniae bacteremia in four liver transplantation patients housed in the same
      ward. Investigation of nursing practices revealed that a common normal-saline
      bag, to which intravenous (iv) tubing and a stopcock were attached, was used to
      flush iv catheters. The iv tubing and stopcock were changed at sporadic
      intervals. Cultures of the normal saline and iv equipment yielded K. pneumoniae,
      which had the same susceptibility pattern as the patients' isolates. Isolates
      recovered during the outbreak from the patients and from the iv saline/equipment
      were of the same strain, as determined by pulsed-field electrophoresis of Xba I
      digested genomic DNA. Termination of the practice of flushing iv catheters with a
      common normal-saline bag halted the outbreak.

PMID- 8749646
TI  - Seizures associated with ofloxacin therapy.
AB  - We describe four patients who had seizures while receiving ofloxacin; no other
      causes were evident. Common factors among all patients included advanced age and
      use of a high-dose regimen. The renal insufficiency of three patients and the
      timing of the seizures implicate accumulation of ofloxacin as a contributing
      factor. Other potentially related factors included electrolyte abnormalities and
      prior neurological insult. Improved awareness of and further investigation into
      the neurotoxic effects of ofloxacin may enhance its safe use.

PMID- 8749647
TI  - Strain variation and antifungal susceptibility among bloodstream isolates of
      Candida species from 21 different medical institutions.
AB  - Variation in the DNA profile and antifungal susceptibility of 271 bloodstream
      isolates of Candida species was evaluated. The isolates were obtained from 152
      nonneutropenic patients hospitalized in 21 different medical centers. In general,
      each patient was infected with their own distinct DNA type of Candida, and in
      those cases in which multiple cultures were positive, the same strain was
      isolated repeatedly over time. Minimum inhibitory concentrations of fluconazole
      or amphotericin B did not increase over time among the strains isolated
      repeatedly from individual patients.

PMID- 8749648
TI  - Cryptococcus neoformans myositis in a patient with AIDS.

PMID- 8749649
TI  - Household transmission of vancomycin-resistant Enterococcus faecium.

PMID- 8749650
TI  - Isolation of a nutritionally aberrant strain of Cryptococcus neoformans from a
      patient with AIDS.

PMID- 8749651
TI  - Outbreak of diarrhea due to Vibrio parahaemolyticus among military personnel in
      Lima, Peru.

PMID- 8749652
TI  - Foscarnet therapy for acyclovir-resistant herpes simplex virus 1 infection in
      allogeneic bone marrow transplant recipients.

PMID- 8749653
TI  - Unusual pigmentation in patients with AIDS who are receiving rifabutin for
      bacteremia due to Mycobacterium avium/Mycobacterium intracellulare complex.

PMID- 8749654
TI  - Atypical infection due to Vibrio cholerae in patients infected with human
      immunodeficiency virus.

PMID- 8749655
TI  - Oral ciprofloxacin therapy for prosthetic valve endocarditis due to
      Actinobacillus actinomycetemcomitans.

PMID- 8749656
TI  - Bacterial pericarditis and cardiac tamponade in patients infected with human
      immunodeficiency virus type 1: case report and review.

PMID- 8749657
TI  - Use of bacitracin therapy for infection due to vancomycin-resistant Enterococcus
      faecium.

PMID- 8749658
TI  - Use of random amplified polymorphic DNA for detection of Trichinella britovi
      outbreaks in Spain.

PMID- 8749659
TI  - Severe sepsis caused by Clostridium sordellii following liver biopsy in a liver
      transplant recipient.

PMID- 8749660
TI  - Pyoderma gangrenosum complicated by underlying osteomyelitis: successful
      treatment with radical surgical debridement and cyclosporine therapy.

PMID- 8749661
TI  - Pulmonary cryptococcosis presenting as pneumothorax in a patient with AIDS.

PMID- 8749662
TI  - Septic arthritis of the sternoclavicular joint.

PMID- 8749663
TI  - Use and standardization of the Mycobacterium avium sensitin skin-test reagent.

PMID- 8749664
TI  - Human immunodeficiency virus infection and porphyria cutanea tarda.

PMID- 8749665
TI  - Detection of Corynebacterium diphtheriae in throat swab specimens from Spanish
      patients infected with human immunodeficiency virus.

PMID- 8749666
TI  - Fungal liver involvement in bone marrow transplant recipients.

PMID- 8749667
TI  - Multiple bacille Calmette-Guerin vaccinations and interpretation of the Mantoux
      test in children.

PMID- 8749668
TI  - The molecular basis of pneumococcal infection: a hypothesis.
AB  - New insight has been gained into the mechanisms underlying the tissue tropism and
      inflammation of pneumococcal infection. Virulence has been linked to a
      transparent colonial morphology. Adherence has been characterized at the
      molecular level, and the importance of receptors arising upon activation of
      eukaryotic cells in promoting the progression to disease has been established.
      The contribution of peptidoglycan and teichoic acid to the generation of
      inflammation has suggested the need to couple anti-inflammatory therapy with
      antibiotic treatment in order to improve the outcome of invasive disease.
      Elucidation of the pathogenesis of pneumococcal infection, including the
      identification of virulence determinants by recently developed genetic
      strategies, can provide a paradigm for new mechanisms that are active in gram
      positive bacterial infections and that are clearly distinct from the familiar
      pathways triggered by endotoxin.

PMID- 8749669
TI  - Effectiveness of control programs for pneumonia among children in China and Fiji.
AB  - This article summarizes the implementation and efficacy of the World Health
      Organization's standard case management program for pediatric pneumonia in three
      counties in China and in the Western Division of Fiji. The information provided
      through this program was simple enough to be understood by parents and health
      care workers with a basic educational background. The program reduced mortality
      from pneumonia even when implemented through the existing health care system in a
      relatively poor county in China. The factors important in the success of the
      program included improved recognition of the signs of childhood pneumonia by
      parents, earlier presentation of children with these signs to health care
      facilities, availability of antimicrobial agents at the primary health care
      level, and rational decisions by health care workers about the use of these
      agents.

PMID- 8749670
TI  - The management of pneumonia in children in developing countries.
AB  - Pneumonia kills about 3 million children every year in developing countries, and
      it is now clear that most fatal pneumonia is caused by Haemophilus influenzae or
      Streptococcus pneumoniae. To reduce mortality associated with pneumonia, the
      World Health Organization has developed guidelines for the treatment of children
      in developing countries who have cough or difficulty breathing: children without
      tachypnea or chest indrawing do not need antibiotic therapy; children with
      tachypnea but no chest indrawing should have antibiotic therapy at home; and
      children with chest indrawing should be admitted to the hospital for
      intramuscular injections of benzylpenicillin or chloramphenicol. Universal
      application of these guidelines would save the lives of approximately 600,000
      children every year. Other important issues are oxygen therapy, fluid
      restriction, limitation of the use of acetaminophen, pneumonia in neonates, and
      the emergence of antibiotic resistance. There is an urgent need for vaccines that
      protect infants against infection with S. pneumoniae and all strains of H.
      influenzae, including nonserotypeable strains.

PMID- 8749671
TI  - Diagnosis and treatment of nosocomial pneumonia in patients in intensive care
      units.
AB  - The optimal management strategy for ventilator-dependent patients who develop
      symptoms suggestive of lung infection remains controversial. Our personal bias is
      that using bronchoscopic techniques to obtain protected-brush and bronchoalveolar
      lavage specimens from the affected area in the lung permits physicians to devise
      a therapeutic strategy that is superior to one based only on clinical evaluation.
      These bronchoscopic techniques, when they are performed before new antibiotics
      are administered, enable physicians to identify most patients who need immediate
      treatment and to select optimal therapy, in a form that is safe and well
      tolerated by patients. Furthermore, they frequently permit physicians to withhold
      antimicrobial treatment from patients without infection, thereby minimizing the
      risk of emergence of resistant microorganisms in the intensive care unit. Despite
      many advances in antimicrobial therapy, successful treatment of patients with
      nosocomial pneumonia remains a complex undertaking, and ultimately further trials
      will be needed to clarify the optimal duration of treatment and the circumstances
      in which monotherapy can be safely used.

PMID- 8749672
TI  - The Streptococcus milleri group as a cause of pulmonary infections.
AB  - Streptococci that colonize the mouth and upper respiratory tract tend to be
      considered harmless commensals. In 45 cases of acute pneumonia and/or pulmonary
      abscess and 25 cases of thoracic empyema, the predominant species recovered were
      anaerobic bacteria and the Streptococcus milleri group, which encompasses the
      oral species Streptococcus anginosus, Streptococcus constellatus, and
      Streptococcus intermedius. The isolation of most S. milleri organisms along with
      oral anaerobes indicated synergy between these groups. Studies in a mouse model
      of pneumonia demonstrated this synergy; mortality was higher, histopathologic
      abnormalities were more marked (reflecting acute pneumonia followed by pulmonary
      abscess or empyema), and viable bacteria were more numerous in the lungs of mice
      with mixed infections caused by the S. milleri group and anaerobes than in the
      lungs of those with monomicrobial infection. In vitro studies elucidated a
      possible mechanism of this synergistic effect: anaerobes may enhance the growth
      of the S. milleri group and/or inhibit the bactericidal activity of the host. We
      conclude that the S. milleri group is more important in pulmonary infections than
      has previously been recognized.

PMID- 8749673
TI  - Pneumonia due to Chlamydia pneumoniae: prevalence, clinical features, diagnosis,
      and treatment.
AB  - The association of Chlamydia pneumoniae with pneumonia was first reported in
      1985. This review summarizes the data collected during the subsequent 10 years on
      the prevalence, clinical features, diagnosis, and treatment of this disease,
      which is now associated with approximately 10% of all cases of pneumonia
      worldwide. Primary infections are documented most often in schoolchildren and
      young adults, while reinfections are prominent among the elderly. C. pneumoniae
      pneumonia is difficult to diagnose; its onset is often insidious, with
      nonpurulent sputum and without leukocytosis. The microbiological diagnosis is
      based on the results of serological tests, polymerase chain reaction, and
      culture. Tetracyclines and macrolides are effective in the treatment of C.
      pneumoniae pneumonia, as are new quinolones.

PMID- 8749674
TI  - Coxiella burnetii (Q fever) pneumonia.
AB  - Pneumonia is one manifestation of acute Q fever following infection with Coxiella
      burnetii. Fever, headache, and myalgia dominate the clinical picture of Q fever
      pneumonia. Cough is nonproductive and may be absent despite the presence of
      pneumonia. While in most instances pneumonia results in an illness of mild-to
      moderate severity, on occasion it is rapidly progressive and results in
      respiratory failure. Infection occurs as a result of inhalation of contaminated
      aerosols. Infected cattle, sheep, and goats are the usual reservoirs for this
      zoonosis. In some areas, infected parturient cats serve as the reservoir, and in
      such instances, rounded opacities are seen on the chest radiograph. The diagnosis
      of C. burnetii pneumonia is usually confirmed by demonstration of a fourfold or
      greater rise in antibody titer. Treatment is usually with a tetracycline or
      rifampin for 7 to 10 days.

PMID- 8749675
TI  - Antimicrobial chemotherapy for legionnaires' disease: a review.
AB  - Controlled trials of antimicrobial chemotherapy for legionnaires' disease have
      not been performed, although erythromycin and tetracycline appear to be effective
      therapies. Laboratory data indicate that the activities of the fluoroquinolone
      and newer macrolide/azalide agents against Legionella pneumophila are superior to
      that of erythromycin, and case reports substantiate that the activities of these
      agents are at least equal. Results of clinical treatment with and laboratory
      testing of macrolides, tetracyclines, co-trimoxazole, chloramphenicol,
      aminoglycosides, fluoroquinolones, beta-lactam agents, and streptogramins are
      reviewed. The drugs of choice for the treatment of legionnaires' disease in
      immunocompromised or severely ill patients should be one of the fluoroquinolone
      antimicrobials rather than erythromycin.

PMID- 8749676
TI  - Medical management of nephropathy in type I diabetes mellitus: current
      recommendations.
AB  - Diabetic nephropathy is the single most common cause of end-stage renal disease
      in the United States. Recently, several major therapeutic interventions have been
      developed and demonstrated to slow or halt the progression of renal failure in
      patients with diabetes and diabetic kidney disease. The Diabetes Control and
      Complications Trial demonstrated that microalbuminuria developed in fewer
      patients in the intensive blood sugar control group than in the conventional
      therapy group. Similarly, the risk of developing proteinuria was reduced by
      intensive blood sugar control. Multiple studies have demonstrated that in
      patients with insulin-dependent diabetes and proteinuria, lowering the systemic
      blood pressure slows the rate of decline in renal function and improves patients'
      survival. In the recently completed trial of ACE inhibition in diabetic
      nephropathy, ACE inhibitors were specifically shown to decrease dramatically the
      risk of doubling of serum creatinine or reaching a combined outcome of end-stage
      renal disease or death. In studies in small numbers of patients with insulin
      dependent diabetes and established diabetic nephropathy, dietary protein
      restriction has also been demonstrated to slow the rate of decline of renal
      function. New potential interventions currently undergoing study include the use
      of aldose reductase inhibitors, the use of drugs that prevent the formation of
      advanced glycosylation end-products, and the use of angiotensin II receptor
      antagonists. Thus, several established benefits have recently been demonstrated
      to help prevent the development of or slow the progression of diabetic
      nephropathy, including blood pressure control, blood sugar control, and treatment
      with ACE inhibitors. Dietary protein restriction may also be of benefit. Multiple
      new interventions are undergoing clinical trials currently.

PMID- 8749677
TI  - A cloned Ca(2+)-sensing receptor: a mediator of direct effects of extracellular
      Ca2+ on renal function?
AB  - Changes in the extracellular calcium concentration [Ca2+]o modulate several
      aspects of renal function through unknown mechanism(s). cDNA encoding a Ca2+o
      sensing receptor from bovine parathyroid and rat kidney that appears to mediate
      several of the known effects of Ca2+o on parathyroid and renal function were
      recently isolated. The expressed receptor activates phospholipase C, showing a
      pharmacologic profile very similar to that of the native receptor. Its deduced
      amino acid sequence identifies it as a member of the superfamily of G protein
      coupled receptors. The physiologic relevance of the receptor has been established
      by the demonstration that mutations in it cause three inherited diseases of
      calcium metabolism. Two hypercalcemic disorders, familial hypocalciuric
      hypercalcemia and neonatal severe hyperparathyroidism, result from inactivating
      mutations when present in the heterozygous and homozygous states, respectively.
      An activating mutation, in contrast, causes an autosomal dominant form of
      hypocalcemia. In the kidney, the receptor is expressed most abundantly in the
      thick ascending limb, where it likely modulates sodium chloride, calcium, and
      magnesium reabsorption and, perhaps, urinary concentrating ability. Studies are
      currently underway to determine whether it also mediates the effects of Ca2+o on
      other parameters of kidney function, such as RBF, glomerular filtration, renin
      secretion, and vitamin D metabolism. Thus, this Ca2+o-sensing receptor permits
      extracellular calcium ions to act not only as an intracellular second messenger
      but also in a "hormone-like" role as an extracellular first messenger.

PMID- 8749678
TI  - Acute renal failure in membranous glomerulonephropathy: a result of superimposed
      crescentic glomerulonephritis.
AB  - A patient who presented with acute renal failure and anasarca secondary to
      crescentic glomerulonephritis superimposed on existing membranous
      glomerulonephropathy of 15 years' duration is described. The patient responded to
      an initial course of prednisone but failed to respond to a second course after
      relapse. The differential diagnosis of acute renal failure in the setting of
      nephrotic syndrome is discussed. Eighteen cases of crescentic glomerulonephritis
      superimposed on membranous glomerulonephropathy are reviewed. The clinical
      setting is heterogeneous with variable presentation and outcome. It appears that
      patients without antiglomerular basement membrane antibodies have a better
      prognosis than those who have antibodies. Patients with membranous
      glomerulonephropathy who develop unexplained acute renal failure should undergo
      early renal biopsy in order to rule out unexpected pathologic complications.

PMID- 8749679
TI  - Properties of electrogenic Pi transport by a human renal brush border Na+/Pi
      transporter.
AB  - Inorganic phosphate (Pi) induced an inward current (IP) in Xenopus oocytes
      expressing the human renal Na+/Pi cotransporter NaPi-3. At 100mM Na+, Pi
      transport was independent of the holding potential and resulted in an apparent Km
      of 0.08 mM; lowering the Na+ concentration to 50 mM resulted in an increase of
      the apparent Km to 0.22 mM at -50 mV and to 0.31 mM at -90 mV. In contrast, the
      apparent Km for Na+ was not significantly influenced by the holding potential. A
      decrease of the pH from 7.8 to 6.8 resulted in a decrease of IP at 50 mM Na+, but
      not at 150 mM Na+. Arsenate induced inward currents through NaPi-3 and decreased
      the apparent Km in measurements of IP. Phosphonoformic acid itself induced no
      currents, but inhibited Pi-induced currents with an apparent Ki of 3.6 mM. In
      summary, NaPi-3 displays characteristic Na+/Pi cotransporter properties with
      relevant interactions with arsenate (transport substrate) and phosphonoformic
      acid (inhibitor). Monovalent and divalent Pi both appear to be transported by
      NaPi-3.

PMID- 8749680
TI  - Natriuretic peptide B receptor and C-type natriuretic peptide in the rat kidney.
AB  - Natriuretic peptide receptor B (ANP-RGC(B)) has been previously identified in the
      kidney. It binds C-type natriuretic peptide (CNP) with high affinity and the two
      other natriuretic peptides (atrial natriuretic peptide and brain natriuretic
      peptide) with low affinity, and mediates the biological effects of CNP. The
      purpose of this investigation was to identify sites of ANP-RGC(B) mRNA in the rat
      renal tubule and to confirm that CNP itself is synthesized in the rat kidney.
      Kidneys from male Sprague-Dawley rats were removed and divided into cortex, outer
      medulla, and inner medulla. Using reverse transcriptase and polymerase chain
      reaction techniques, ANP-RGC(B) mRNA was identified in the three principal
      regions of the kidney. Individual glomeruli and segments of the renal tubule were
      microdissected and subjected to reverse transcriptase-polymerase chain reaction.
      ANP-RGC(B) mRNA was regularly found (>60% of animals) in glomeruli, distal
      convoluted tubule, and cortical, outer medullary, and inner medullary tubules but
      not in the proximal convoluted tubule, proximal straight tubule, thin or
      medullary thick ascending limb. ANP-RGC(B) mRNA was also identified in outer
      medullary descending vasa recta. Glyceraldehyde-3-phosphate-dehydrogenase and
      natriuretic peptide A receptor mRNA were present in all segments. In a separate
      study, CNP mRNA was identified in whole kidney, cortex, and medulla. These
      findings confirm that CNP and its receptor are present in the rat kidney. The
      proximity of the ligand and receptor suggests that CNP may have paracrine or
      autocrine regulatory functions in the rat kidney.

PMID- 8749681
TI  - Activators of protein kinase A and of protein kinase C inhibit MDCK cell myo
      inositol and betaine uptake.
AB  - Amino acid sequences of the myo-inositol and betaine cotransporters that are
      induced in MDCK cells by hypertonicity include consensus sequences for
      phosphorylation by protein kinase A and by protein kinase C. To test for the
      effect of activation of protein kinases A and C on the activity of those
      cotransporters, MDCK cells were exposed to activators of each kinase and the
      activity of both cotransporters was assayed. Incubation with 8-bromoadenosine
      3':5'-cyclic monophosphate (8Br-cAMP) or 3-isobutyl-1-methylxanthine (IBMX),
      activators of protein kinase A, and incubation with an active phorbol ester or
      with an active diacylglycerol, activators of protein kinase C, inhibited the
      activity of both cotransporters by about 30%. The relative effect of the
      activation of protein kinase A and of protein kinase C was similar in hypertonic
      and isotonic cells. The effects of activators of protein kinase A and of protein
      kinase C were not additive. The two cotransporters behaved differently when
      protein kinase C activity was down-regulated by prolonged incubation with a
      higher concentration of phorbol 12-myristate 13-acetate. There was a doubling of
      activity of the myo-inositol cotransporter and no change in the activity of the
      betaine cotransporter in hypertonic and isotonic cells. Although the mechanisms
      of the effects of activation of the two kinases remain to be established, it is
      clear that the kinases can mediate post-translational regulation of the uptake of
      compatible osmolytes.

PMID- 8749682
TI  - Presence and regulation of Raf-1-K (Kinase), MAPK-K, MAP-K, and S6-K in rat
      nephron segments.
AB  - Renal nephron segments are heterogeneous, and receptors for endothelin (ET)-1, ET
      3, Angiotensin II (AII), epidermal growth factor (EGF), and insulin-like growth
      factor I distribute differently along the nephron segments. Recently, growth
      factors and vasoactive substances are reported to stimulate mitogen-activated
      protein kinase (MAP-K). In this study, we showed that mRNA and proteins of MEK-K,
      Raf-1-K, MAPK-K, MAP-K (p42 and p44), and S6-K are expressed ubiquitously in
      intact nephron segment. We demonstrated that four tiers of a cascade composed of
      the Raf-1-K, MAP-K, MAP-K, and S6-K are stimulated by ET-1 and ET-3 in rat intact
      glomeruli (Glm) via primarily B-type ET receptors and PKC. The stimulatory effect
      of EGF and IGF-I to MAP-K activity is inhibited by a tyrosine kinase inhibitor in
      Glm. IGF-I significantly stimulates MAP-K activity and EGF and All moderately
      stimulate MAP-K activity in the proximal convoluted tubule (PCT). EGF
      significantly increased MAP-K cascades and ET-1 and ET-3 slightly increased MAP-K
      cascades in the medullary thick ascending limb (MTAL). EGF significantly
      stimulated MAP-K cascades, and ET-1 and ET-3 moderately stimulate MAP-K cascades
      in the outer medullary collecting duct (OMCD) and the inner medullary collecting
      duct (IMCD). MAPK-K and S6-K are similarly stimulated by these agonists in each
      segment. This study shows that MAP-K cascades are expressed in every nephron
      segment. ET-1, ET-3, All, EGF, and IGF-I stimulate MAP-K cascades heterogeneously
      along the nephron segment. It was concluded that MAP-K cascades play an important
      role in the regulation of renal function.

PMID- 8749683
TI  - The use of heated citric acid for dialyzer reprocessing.
AB  - Dialyzer reprocessing with heated water (100 to 105 degrees C) for 20 h can be
      used safely in lieu of chemical methods for disinfection. All infective agents
      including spores are destroyed and depyrogenation may occur. However, these
      temperatures may result in structural damage to the dialyzer, limiting reuse.
      Dialyzer reprocessing by using 1.5% citric acid heated to 95 degrees C for 20 h
      is an alternative method that produces equivalent microbiologic effects. Citric
      acid is well known as a disinfecting agent used for dialysis equipment. Because
      there is little structural damage to dialyzer components at 95 degrees C, reuse
      statistics are improved (mean reuse increased to 12.8). Both small and large
      molecule clearances and the sieving coefficient for protein are insignificantly
      altered by the process. Whereas the procedure is relatively simple, quality
      assurance indicators are essential. The method has appeal because it avoids the
      use of chemical germicides. However, at present it has only been tested
      thoroughly in polysulfone dialyzers with heat-resistant polycarbonate casings and
      polyurethane resin. The clinical experience is favorable.

PMID- 8749684
TI  - Cell aggregation and apoptosis induced by hemodialysis membranes.
AB  - During hemodialysis, circulating mononuclear cells can be stimulated to different
      degrees, depending on membrane biocompatibility. Cell activation usually leads to
      aggregation and proliferation. It may also result in apoptosis if cells are
      subjected to abnormal activation. This may be the case of cells exposed to
      bioincompatible hemodialysis membranes. The study presented here evaluates the
      effects of two hemodialysis membranes, with different degrees of
      biocompatibility, (Cuprophan (CU; Lundia IC 5N; GAMBRO, Sweden) and
      polyacrylonitrile (AN69; Biospal 3000S, Hospal, France)) on aggregation and
      apoptosis of circulating human mononuclear cells and the human mononuclear cell
      line (THP-1). The results showed that 2-h incubation with CU, a bioincompatible
      membrane, produces cell aggregation of both peripheral mononuclear cells and THP
      1 cells (35% and 54%, respectively). After 48 h of incubation with a CU membrane,
      apoptotic death was observed in 32% of THP-1 cells and in 45% of normal
      peripheral mononuclear cells. Neither cell aggregation nor apoptosis was observed
      after incubation with the AN69 membrane. CU membrane-induced apoptosis was
      inhibited by Staurosporrin (Sigma, St. Louis, MO) a protein kinase C (PKC)
      inhibitor, suggesting that cell apoptosis induced by the CU membrane is mediated
      by a PKC-dependent cell activation. Furthermore, cell prestimulation with phorbol
      12-myristate 13-acetate, an activator of PKC, results in a increase in the
      percentage of THP-1 cell death by apoptosis after CU exposure (53%). Our study
      indicates that CU membranes induce mononuclear cell activation, leading to cell
      apoptosis.

PMID- 8749685
TI  - Effect of immunoglobulin light chains from hemodialysis and continuous ambulatory
      peritoneal dialysis patients on polymorphonuclear leukocyte functions.
AB  - Circulating plasma factors accumulating in the serum of uremic patients have the
      potential to inhibit essential functions of polymorphonuclear leukocytes (PMNL).
      As a consequence, these factors can contribute to the increased risk for
      bacterial infections generally found in uremic patients. Free immunoglobulin
      light chains that are present in the serum of healthy adults at low levels appear
      in the serum of uremic patients at significantly higher levels. Therefore, kappa
      and lambda light chains in their monomeric and dimeric forms were isolated from
      hemodialysis and continuous ambulatory peritoneal dialysis patients and their
      potential to inhibit essential PMNL functions in in vitro assays was tested. It
      was found that all isolates tested were able to inhibit deoxyglucose uptake, a
      measure for the state of activation of PMNL, as well as chemotaxis. In contrast,
      free immunoglobulin light chains had no influence on the phagocytotic functions
      of PMNL. It was concluded that free immunoglobulin light chains are able to act
      as uremic toxins by interfering with essential PMNL functions and that their
      serum levels and fate during the treatment of uremic patients should be taken
      into consideration.

PMID- 8749686
TI  - Cerebral edema after rapid dialysis is not caused by an increase in brain organic
      osmolytes.
AB  - Dialysis disequilibrium syndrome (DDS) is characterized by the neurologic
      deterioration and cerebral edema that occurs after hemodialysis. To investigate
      the pathogenesis of DDS, the effects of rapid hemodialysis on brain electrolytes,
      urea, and several organic osmolytes were studied in the rat. Forty-two h after
      bilateral ureteral ligation, 11 uremic rats were hemodialyzed for 90 min,
      yielding a decrease in plasma urea from 96 +/- 4 to 44 +/- 5 mM (p < 0.01). This
      group was compared with 10 uremic and 11 nonuremic animals that were not
      dialyzed. In dialyzed animals, compared with nondialyzed uremic controls, there
      was an increase in brain water (3.98 +/- 0.02 versus 3.77 +/- 0.02 L/kg dry wt; P
      < 0.01) and the brain to plasma (urea) ratio (1.32 versus 0.65). There was no
      significant difference in the brain content of sodium and potassium between
      groups. The retention of brain urea, despite the large decrease in plasma urea
      concentration, was able to account for the increase in brain water observed in
      rapidly dialyzed animals. Major organic osmolytes in the brain, including
      glutamine, glutamate, taurine and myoinositol, did not increase significantly
      after rapid dialysis. Cerebral edema in this model of DDS was primarily due to a
      large brain-to-plasma urea gradient, not to the formation of organic osmolytes.

PMID- 8749687
TI  - Correcting acidosis in hemodialysis: effect on phosphate clearance and
      calcification risk.
AB  - Control of uremic acidosis by hemodialysis carries the potential risks of
      reducing phosphate clearance and worsening metastatic calcification; modeling
      bicarbonate delivery has been proposed to adequately correct acidosis without
      impairing phosphate removal. To test the efficacy and safety of different methods
      for controlling acidosis, nine stable adults received in random order standard
      (S; dialysate HCO3- 30 to 34 mmol/L), high (H; 40 mmol/L) or modeled (M; 28
      mmol/L, rising exponentially to 35 mmol/L at 3 h, 40 mmol/L at 4 h) bicarbonate
      dialysis for 4 wk each, and were tested during the last two dialyses of each
      treatment. More oral bicarbonate capsules were required with M than H (2.8 +/-
      0.4 versus 1.4 +/- 0.4/day, P = 0.04) to maintain predialysis HCO3- at 24 to 26
      mmol/L. Plasma HCO3- was significantly higher with H than M during dialysis, and
      than S before, during, and after dialysis. Plasma inorganic phosphate, phosphate
      rebound, clearance of phosphate from plasma (80 to 90 mL/min) and mass transfer
      of phosphate into dialysate (12 to 13 mmol/4 h dialysis) were no different among
      the three treatments. Similarly, there were no differences in plasma
      concentration of urea, total calcium, estimated ionized calcium, lipids, and
      potassium, clearance and mass transfer of urea, blood pressure, and symptoms with
      the three treatments. Estimated levels of tribasic inorganic phosphate, the
      phosphate component of hydroxyapatite, were very similar before and after each
      treatment. Plasma calcium x phosphate product was less than 3.5 mmol2/L2 at all
      times with each treatment. A risk factor for metastatic calcification was
      calculated from the relative saturation ratio of its principle component,
      hydroxyapatite (Ca5 (PO4)3 OH); this was no different among each of the
      treatments, and was not altered significantly by dialysis. Uremic acidosis can be
      fully corrected by high or modeled bicarbonate dialysis without any reduction of
      phosphate clearance or increased risk of metastatic calcification. The added cost
      of modeling technology is not justified by the criterion of phosphate clearance
      alone.

PMID- 8749688
TI  - Parameters of prognostic relevance to the patency of vascular access in
      hemodialysis patients.
AB  - The objectives of this study were to evaluate whether age, sex, underlying renal
      disease, or the performing surgeon is of prognostic relevance to the patency of
      the vascular access. In a routine clinical setting, 139 first and 144 further
      fistula operations were done in 139 patients during 5 yr and were analyzed in
      retrospect. Within a group of 108 patients with first Cimino-Brescia fistulae,
      Cox multivariate regression analysis revealed the surgeon to be the only
      determinant with a continuous, significant effect on fistula patency throughout
      the observation period (P(out) < 0.1). The patency rates of the seven surgeons at
      1, 2, and 3 yr differed from 34 to 69, 13 to 62, and 13 to 62%, respectively.
      Hazard ratios among the surgeons varied from 0.65 to 2.21. Additionally, age (P <
      0.004) and diabetes mellitus (P < 0.02) were disclosed to be significant risk
      factors for impaired patency, but later in the course of disease (time
      dependent). Sex had no influence. After the failure of the first fistula,
      revisions of or new Cimino-Brescia fistulae (N = 56) were superior to
      polytetrafluoroethylene grafts (N = 61). The mean patency of the former amounted
      to 320 +/- 377 versus 156 +/- 281 days in polytetrafluoroethylene grafts (P <
      0.05). It was concluded that increasing age and diabetes mellitus are time
      dependent risk factors for the shortened patency of arteriovenous fistulae. The
      operating surgeon, however, seems to be the major determinant for the continuous
      patency of Cimino-Brescia fistulae.

PMID- 8749689
TI  - Thrombolysis versus surgery for the treatment of thrombosed dialysis access
      grafts.
AB  - Thrombolysis offers several advantages over surgery in the treatment of
      thrombosed dialysis access grafts. This study was undertaken to compare the
      results obtained when thrombolysis was used as the preferred treatment
      (Thrombolysis Period) for this problem in comparison with the results that had
      been obtained when surgical therapy had been the preferred treatment (Surgery
      Period). Each period of study lasted 12 months and the two periods ran
      consecutively. All data were collected prospectively. No significant problems
      were encountered when thrombolysis was substituted for surgical therapy as the
      preferred treatment of thrombosed dialysis access grafts. During the Surgical
      Period there were 580 thrombotic episodes, a rate of 0.86 per patient. During the
      Thrombolysis Period there were 568 episodes, a rate of 0.76. These differences
      were not statistically significant. During the Thrombolysis Period, thrombolysis
      was found to be as effective as surgery had been during the Surgical Period in
      the initial treatment of thrombosed grafts. The rate of surgical revision was
      decreased by two-thirds during the Thrombolysis Period, but the rate of graft
      replacement was not altered. Long-term patency after therapy by thrombolysis
      during the Thrombolysis Period was superior to that for surgical thrombectomy
      performed during the Surgical Period, and was equal to that for revision and
      graft replacement. The complication rate for thrombolysis was low and
      complications were managed easily without sequelae. It is concluded that
      thrombolysis is safe and, when used as the preferred treatment for thrombosed
      dialysis access grafts, is as effective as surgical therapy. Since it preserves
      potential vascular access sites and yields long-term patency rates superior to
      those for surgical thrombectomy, it should be regarded as the treatment of choice
      for this problem.

PMID- 8749690
TI  - Anastomotic intimal hyperplasia in prosthetic arteriovenous fistulas for
      hemodialysis is associated with initial high flow velocity and not with mismatch
      in elastic properties.
AB  - Stenotic intimal thickening at the venous end of prosthetic arteriovenous (AV)
      fistulas for hemodialysis has been associated with perianastomotic mismatch in
      elastic properties, and low shear rates. In a prospective way, the role of these
      factors on the occurrence of intimal hyperplasia in prosthetic AV fistulas in
      hemodialysis patients was investigated. In 24 hemodialysis patients, the elastic
      properties were assessed in the distal graft segment and the outflow vein
      postoperatively with the use of Vessel Wall Doppler Tracking (VWDT), a
      noninvasive ultrasound technique. In addition, normalized peak systolic velocity
      (nPSV) was calculated from diameter (VWDT) and peak systolic velocity. The
      initial mismatch around the venous anastomoses and local nPSV were correlated
      with the occurrence of stenoses during follow-up (2 yr). The detection of a
      stenosis was performed with both Duplex ultrasound and angiography. In four
      cases, a stenosis developed in the venous anastomosis; in eight cases, a stenosis
      developed in the venous outflow segment; and in four cases, stenoses developed at
      both sites. A better initial match in elastic properties around the venous
      anastomosis was observed in the fistulas developing a stenosis at this site as
      compared with the nonstenotic fistulas (P < 0.05). The initial local nPSV values
      at the site of the later stenosis were higher in the fistulas developing a
      stenosis as compared with the nonstenotic fistulas (P < 0.05). It was concluded
      that the occurrence of stenoses in prosthetic AV fistulas for hemodialysis in or
      adjacent to the venous anastomoses is associated with a high initial flow
      velocity but not with a mismatch in elastic properties.

PMID- 8749691
TI  - Factors influencing progression of renal failure in autosomal dominant polycystic
      kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) frequently leads to end
      stage renal failure (ESRF) in the sixth decade of life, but considerable
      heterogeneity exists in the rate of progression of renal failure. The respective
      contribution of genetic factors and of potentially amendable factors, such as
      blood pressure control or protein intake limitation, on the rate of progression
      in ADPKD patients is still debated. To evaluate the role of factors influencing
      the rate of progression of renal failure in ADPKD, we retrospectively analyzed
      the annual rate of decline of creatinine clearance (Ccr) in 109 ADPKD patients
      followed from the time a Ccr value of 30 to 50 mL per min/1.73 m2 was measured
      until ESRD and need for hemodialysis (Study A), and in 48 undialyzed ADPKD
      patients followed for at least 4 yr from the time a Ccr value of 50 to 60 mL per
      min/1.73 m2 was measured (Study B). In Study A, the decline in Ccr (delta Ccr)
      (mean +/- SE) was 5.8 +/- 0.2 mL per min/1.73 m2 per year in the whole series,
      and was lower in females than in males (5.0 +/- 0.2 versus 6.4 +/- 0.2, P <
      0.001). Accordingly, ESRF was reached at a later age in female patients (55.1 +/-
      1.2 versus 50.6 +/- 1.2 yr, P < 0.01). The age at ESRF in male patients was lower
      when the disease was transmitted by mother than by father (46.3 +/- 1.9 versus
      54.1 +/- 1.8 yr, P < 0.01), whereas no significant effect of the gender of the
      affected parent was apparent in female patients. By regression analysis, there
      was a positive but weak relationship between delta Ccr and mean arterial pressure
      (average value during follow-up, 107 +/- 1 mm Hg, r = 0.224, P < 0.05) but not
      with dietary protein intake (mean value in follow-up, 0.87 +/- 0.03 g/kg per day,
      r = 0.10, P = 0.33) nor with proteinuria at baseline, which was lower than 0.3
      g/day in 104 cases (r = 0.10, P = 0.28). There was a negative relationship
      between age at ESRF and delta Ccr (r = 0.245, P < 0.05), with a later and slower
      progression in older subjects. In Study B, the mean decline in renal function
      during follow-up was 5.3 +/- 0.4 mL/min/1.73 m2 per year, a value close to that
      observed in Study A. By multiple regression analysis of the overall population
      (studies A and B combined), only MAP, age and gender were independent predictive
      factors of delta Ccr but all studied parameters taken together accounted for at
      best 20% of delta Ccr variation. We conclude that the rate of progression of
      renal failure in ADPKD patients is mainly determined by gene expression, with
      female gender and older age associated with a slower progression, whereas blood
      pressure control, but not protein intake, exerts a limited beneficial influence
      on the rate of progression in patients with advanced polycystic kidney disease
      who already have significant renal insufficiency.

PMID- 8749692
TI  - More adverse renal prognosis of autosomal dominant polycystic kidney disease in
      families with primary hypertension.
AB  - Marked variability of age at renal death is noted in autosomal dominant
      polycystic kidney disease (ADPKD). The hypothesis that the coexistence of primary
      hypertension and ADPKD within families is associated with earlier renal death was
      tested. Of a total of 162 ADPKD patients treated in one Austrian and three German
      centers, 57 propositi were identified whose families provided (1) information
      concerning blood pressure; (2) documented presence of ADPKD (by sonography or
      autopsy) in one parent; and (3) age at renal death in the propositus.
      Hypertension of the unaffected parent was defined as blood pressure above 140/90
      mm Hg or antihypertensive treatment before age 60 yr. Age at renal death in the
      propositus was defined as the start of renal replacement therapy. Median age at
      renal death of 23 offspring (11 male, 12 female) from families with a history of
      primary hypertension of the nonaffected parent was lower than that of 34
      offspring (16 male, 18 female) from families without a known history of primary
      hypertension of the nonaffected parent, i.e., 49 yr (26 to 64) versus 54 yr (28
      to 82) (P < 0.03). The data are consistent with the notion that genetic
      predisposition to primary hypertension is associated with an earlier onset of
      terminal renal failure in families with ADPKD.

PMID- 8749693
TI  - Amelioration of polycystic kidney disease by modification of dietary protein
      intake in the rat.
AB  - Polycystic kidney disease is the most common potentially lethal single- gene
      inherited disease in man. There is no specific therapy. Previous studies in the
      pcy mouse model of polycystic kidney disease have shown amelioration of cystic
      change by reduction in dietary protein intake. The Han:SPRD-cy rat is a model of
      autosomal dominant polycystic kidney disease that closely resembles human disease
      in its histology and clinical course. We compared the morphometric assessment of
      cystic change and standard laboratory measures of renal function in heterozygous
      Han: SPRD-cy rats that received isocaloric diets containing either 8% or 20%
      protein as casein. This level of dietary protein restriction was associated with
      a significant reduction of mean body weight in the 8% protein group (358 g)
      compared with 20% protein (490 g; P = 0.027). Mean renal volume, adjusted for the
      difference in body weight, was significantly lower in the 8% protein group (6.2
      mL/kg) compared with the 20% protein group (11.6 mL/kg; P = 0.016). The major
      component in this reduction was a reduction in total cyst volume to a mean 0.47
      mL in the 8% protein group from 2.68 mL in the 20% protein group (P < 0.0001).
      All 8% protein diet animals survived to 6 months of age, but 3 of 11 20% protein
      diet animals died between 5 and 6 months of age. Mean serum creatinine and urea
      levels were significantly lower in the 8% protein group (118 mmol/L and 15.6
      mmol/L) compared with the 20% protein group (272 mmol/L, P = 0.0033, and 81.5
      mmol/L, P = 0.0002, respectively). Dietary protein restriction is a potent method
      for modifying the course of polycystic kidney disease in the Han:SPRD-cy/+ rat.
      These findings emphasize the potential for diet to alter the physiology of the
      renal tubulointerstitium.

PMID- 8749694
TI  - Marked enzymuria after bone marrow transplantation: a correlate of veno-occlusive
      disease-induced "hepatorenal syndrome".
AB  - During the first month after bone marrow transplantation, approximately 15% of
      patients develop acute renal failure (ARF). This usually occurs in the setting of
      hepatic veno-occlusive disease (VOD). Prior clinical data have suggested that
      this form of ARF has a hemodynamic basis, analogous to the hepatorenal syndrome
      (HRS). If so, then proximal tubular injury would not be expected. To directly
      test this hypothesis, enzymuria (N-acetyl-beta-D-glucosaminidase [NAG]) was
      quantitated in the following groups of patients within the first 35 days after
      BMT: (1) VOD+ARF (serum creatinine level > 1.5 mg/dL; N = 10); (2) VOD with
      relatively normal renal function (serum creatinine level < 1.5 mg/dL; N = 11);
      and (3) patients without hepatic or renal complications (BMT controls; N = 12).
      For comparison, NAG was also quantitated in the following groups of non-BMT
      patients: (1) toxic/ischemic acute tubular necrosis (ATN) (N = 10); (2) jaundice
      without azotemia (N = 5); and (3) HRS (N = 6). Urine samples from eight healthy
      subjects established normal NAG concentrations (2.5 +/- 0.5 microU/mg urinary
      creatinine; mean +/- SE). All non-BMT patients with ATN had markedly elevated NAG
      levels (61 +/- 12; P < 0.001), validating the test as a marker of tubular damage.
      NAG concentrations were significantly elevated in all of the control BMT patients
      (24 +/- 3; P < 0.01), and the presence of VOD was associated with further
      striking increments (approximately 50 times normal). However, the degree of
      enzymuria was virtually identical for VOD patients with (125 +/- 27) and without
      (122 +/- 17) ARF. Jaundice in a non-BMT setting was associated with only mild NAG
      elevations (11 +/- 2). However, striking enzymuria was noted in all HRS patients
      (61 +/- 20), equaling the levels seen with ATN. The following conclusions were
      derived: (1) subclinical tubular injury, as defined by enzymuria, appears to be
      ubiquitous after BMT; (2) VOD dramatically increases the extent of enzymuria; (3)
      the degree of enzymuria in VOD patients is not correlated with renal dysfunction,
      implying that the associated ARF has a large hemodynamic component; and (4) HRS
      and ATN manifest comparable degrees of enzymuria, suggesting that substantial
      tubular damage exists in both of these forms of ARF.

PMID- 8749695
TI  - Evaluation of renal function in 60 long-term survivors of bone marrow
      transplantation.
AB  - Although the acute nephrotoxicity of bone marrow transplantation is well
      documented, long-term follow-up studies are scanty. Renal function was evaluated
      in 60 long-term survivors of allogeneic (24 patients) or autologous (36 patients)
      bone marrow transplantation (BMT) with a mean follow-up of 2 yr. Renal function
      tests included serum creatinine, GFR (inulin clearance), effective RPF (p
      aminohyppurate clearance), urinary beta 2-microglobulin and N-acetyl-beta-D
      glucosaminidase excretion, and renal tomography. The mean serum creatinine level
      was 83 +/- 3 and 93 +/- 3 mumol/L before and after grafting, respectively (P <
      0.05). The mean GFR (93 +/- 3 mL/min) and effective RPF (419 +/- 16 mL/min) were
      significantly lower than in healthy controls (120 +/- 3 and 500 +/- 1 mL/min; P <
      0.05) and than in candidates for BMT matched for age and hematologic diseases
      (117 +/- 3 and 469 +/- 11 mL/min; P < 0.05). Thirty-four patients had a fall in
      the GFR of at least 20%. Patients who received total body irradiation had
      significant lower creatinine clearance (86 +/- 3 mL/min) and GFR (86 +/- 3
      mL/min) than the controls and the patients who received high-dose chemotherapy
      (100 +/- 4 and 104 +/- 5 mL/min; P < 0.05). These results suggest that
      subclinical renal dysfunction occurs frequently in marrow graft recipients,
      especially those who undergo total body irradiation.

PMID- 8749696
TI  - Urinary excretion of beta 2-microglobulin predicts renal outcome in patients with
      idiopathic membranous nephropathy.
AB  - In patients with membranous nephropathy, treatment should be limited to those at
      risk for disease progression. Urinary beta 2-microglobulin excretion was measured
      in 30 patients with membranous nephropathy, a nephrotic syndrome, and normal
      renal function (endogenous creatinine clearance > 80 mL/min), who were
      subsequently monitored for a median of 48 months. Renal function deteriorated in
      11 of the 14 patients with a beta 2-microglobulin excretion > 500 ng/min and in
      only 2 of the 16 patients with a beta 2-microglobulin excretion < or = 500 ng/min
      (P < 0.001). The measurement of urinary beta 2-microglobulin excretion thus
      contributes to the identification of patients with membranous nephropathy at high
      risk for developing renal insufficiency and may provide guidance for early
      immunosuppressive treatment.

PMID- 8749697
TI  - Intracranial aneurysms in polycystic kidney disease linked to chromosome 4.
AB  - Autosomal dominant polycystic kidney disease is genetically heterogenous, with at
      least two chromosomal loci accounting for the disease. When the mutation is
      located on chromosome 16 (PKD1), extra-renal manifestations such as the rupture
      of intracranial aneurysms are well known. In the case of localization on
      chromosome 4 (PKD2), in which the renal disease runs a milder course, not much is
      known about the incidence of extrarenal manifestations. A PKD2 family is reported
      in which two members had subarachnoidal bleeding due to intracranial aneurysms;
      there was strong clinical evidence of subarachnoidal bleeding in a third family
      member. This indicates that the familial clustering of intracranial aneurysms may
      also occur in PKD2 families. Because of the considerable mortality and morbidity
      of intracranial aneurysms, screening with magnetic resonance angiography in PKD2
      patients with a positive family history of intracranial aneurysms is recommended.

PMID- 8749698
TI  - Association of angiotensin I-converting enzyme gene polymorphism with
      susceptibility to antiproteinuric effect of angiotensin I-converting enzyme
      inhibitors in patients with proteinuria.
AB  - The antiproteinuric effect of angiotensin I-converting enzyme (ACE) inhibitors in
      patients with renal diseases of various origins has been well recognized.
      However, individual responses regarding the degree of decrease in urinary protein
      excretion appear to vary considerably. The mechanism underlying this variable
      response to ACE inhibitors has not been clarified yet. A possible role of ACE
      gene insertion/deletion (I/D) polymorphism in the responsiveness to
      antiproteinuric effect of ACE inhibitors is examined. Thirty-six patients with
      proteinuria (23 men and 13 woman; mean age, 47 +/- 13 yr) were studied. These
      patients were classified into two groups on the basis of the percent decrease in
      their urinary protein excretion: the effective group, those with a decrease in
      proteinuria (18 patients, -64 +/- 19%) and the noneffective group (18 patients,
      +13 +/- 40%). A 287-base pair (bp) I/D polymorphism in the ACE gene was examined
      by polymerase chain reaction. The allelic frequencies of the ACE gene were I/D =
      0.53/0.47 in the effective group and I/D = 0.81/0.19 in the noneffective group.
      The difference in the allelic frequencies between the two groups was significant
      (chi 2 = 6.25, P = 0.0114 < 0.05). Furthermore, the difference in the
      responsiveness of proteinuria to ACE inhibition between genotype II versus
      genotype ID + DD was statistically significant (chi 2 = 4.05, P = 0.0442 < 0.05).
      There was no significant difference between the two groups with regard to initial
      urinary protein level, blood pressure, renal function, and daily sodium intake.
      The genetic susceptibility to the antihypertensive effect of ACE inhibitors was
      also studied, but no significant relation was observed. This study suggests the
      association of ACE gene I/D polymorphism with the antiproteinuric efficacy of ACE
      inhibitors in patients with proteinuria.

PMID- 8749699
TI  - Acute renal failure after binge drinking and NSAID use.

PMID- 8749700
TI  - The ambiguities of predicting total body water and body cell mass with a single
      frequency (50KHz) measurement of bioimpedance.

PMID- 8749701
TI  - Some preliminary findings concerning a new scale for the assessment of depression
      and related symptoms in stroke patients.
AB  - The authors describe a new scale, the Post-Stroke Depression Rating Scale
      (PSDRS), specifically constructed to investigate the emotional, affective and
      vegetative disorders of stroke patients. They also report some preliminary data
      concerning the validity and reliability of the new scale and of its sections and
      the first results obtained administering the PSDRS to 68 stroke patients and 10
      subjects affected by a "functional" form of major depression. The comparison
      between the results obtained on the PSDRS by patients classified (on the basis of
      DSM III diagnostic criteria) as having major depression of either vascular or
      functional origin seems to show an incomplete overlap between these two forms of
      depression. In patients classified as having major post-stroke depression, part
      of the symptomatology seems to be due either to the direct effect of the brain
      lesion or to the psychological reaction of the patient to the disabilities and
      handicaps provoked by the lesion.

PMID- 8749702
TI  - Status epilepticus in acute ischemic stroke.
AB  - Stroke is one of the most frequent causes of acute symptomatic status
      epilepticus. The aim of this study was to investigate the electroclinical
      features of status epilepticus in acute ischemic stroke. Nine consecutively
      admitted patients with status epilepticus during ischemic stroke were examined:
      five of them had convulsive unilateral or generalized status epilepticus for from
      24 hours to 9 days after a large hemispheric infarction, always associated with
      EEG epileptiform abnormalities; the remaining four had focal motor status
      epilepticus during the first 24 hours after a small cortical or subcortical
      infarction, and showed no clear EEG changes. Status epilepticus in acute ischemic
      stroke may have two distinct electroclinical patterns of different prognostic
      significance.

PMID- 8749703
TI  - A study of symptomatic drug use in migraine without aura.
AB  - We assessed the attack drugs taken by 200 migraine without aura patients
      (International Headache Society criteria, 1988) between 1989 and 1991. A detailed
      pharmacological history regarding the acute attack therapy adopted up until our
      initial visit was gathered, including the type of drug used, dosage,
      administration route, the time of starting therapy, treatment efficacy, and the
      frequency and types of undesirable effects, all of which were subsequently
      compared with the guidelines (1993) of the Italian Society for the Study of
      Headache (SISC). The most commonly used are non steroidal anti-inflammatory drugs
      (NSAIDs). We observed a similar high frequency in the use of combinations,
      particularly prophyphenazone and barbituric acid. The pirazolones, such as
      noramidopyrine and prophyphenazone, are also widely used as single agents, even
      though they are not considered by the guidelines. Our study underlines the fact
      that current drug use differs in several respects from the guidelines.

PMID- 8749704
TI  - Kennedy's disease: clinical and molecular study of two Italian families.
AB  - Kennedy's disease, or spinal and bulbar muscular atrophy (SBMA), is a rare X
      linked motoneuron disorder with variable signs of androgen insensitivity. It is
      associated with the expansion of a trinucleotide CAG repeat within the androgen
      receptor (AR) gene. We here report our clinical and molecular findings in two
      Italian families with Kennedy's disease. The increased size of the CAG repeat was
      demonstrated in four affected males and seven carrier females.

PMID- 8749705
TI  - Rehabilitation: the Cinderella of neurological research? A bibliometric study.
AB  - Rehabilitation is under-represented in the neurological literature on disabling
      diseases. A Medline search was conducted to retrieve the articles published
      between January 1991 and June 1994 under the main headings of Stroke, Parkinson's
      disease, Multiple sclerosis, Brain injury, Ataxia and Dementia. These were then
      combined with the sub-heading Rehabilitation. The former search yielded 27724
      articles, the latter 1272 (4.6%). In 1992, the Journal of Citation Reports (JCR)
      assigned to Journals publishing rehabilitation papers an average Impact Factor
      (IF) of 0.7-2.8 (median 1.8): that is, 31-90% (depending on the various main
      headings, median 68%) of the average IF given to Journals publishing non
      rehabilitation papers. In the present study, the weight of the literature was
      defined as the product of the number of articles multiplied by the IF of the
      corresponding Journal (IF = 0 for non-JCR Journals). Across the various
      neurologic conditions, the weight of the Rehab literature was 0.1-7% (median 2%)
      of the weight of the non-Rehab literature. The results suggest that neurology is
      still reluctant to face the disability challenge.

PMID- 8749706
TI  - Evidence for a missed signal to the CD8+ cells in CSF of multiple sclerosis
      patients.
AB  - Peripheral blood (PB) and cerebrospinal fluid (CSF) lymphocyte subpopulations,
      defined by various T-cell specific monoclonal antibodies and flow cytometry, were
      analysed in 44 relapsing remitting multiple sclerosis (RRMS) patients (including
      21 subjects in the acute phase and 23 in the stable phase), 40 chronic
      progressive multiple sclerosis (CPMS) patients, and 24 patients with other
      neurological diseases (OND), in order to verify the presence of any abnormality
      in the lymphocyte subset pattern. A significant increase in the total number of T
      lymphocytes and the CD4+ subpopulation was found in the PB of the MS patients in
      comparison with the OND group. Moreover, a not statistically significant increase
      in CD4+ cells was observed in the CSF of MS patients. A statistically significant
      increase was also found in the CD4+ Leu 8+ (suppressor inducer) cells in the CSF
      of all of the MS groups. Finally, the CD8+ (suppressor/cytotoxic) cell levels,
      were significantly lower in the CSF of CPMS and stable RMS patients than in the
      CSF of the OND patients. As a whole, our data suggest that the immunosuppressive
      deficit that seems to be a constant finding in MS is not due to a decrease in
      suppressor inducer cell levels, as previously suggested, but may be caused by a
      missed or altered signal from the suppressor inducer to CD8+ suppressor cells.

PMID- 8749707
TI  - High dose intravenous immune globulins and plasma exchange in Guillain-Barre
      Syndrome.
AB  - We report the effects of treatment with plasma-exchange (PE) and intravenous
      immune globulins (IVIg) in 36 out of 50 patients with Guillain-Barre syndrome
      (GBS) recruited by an incidence study in the Emilia-Romagna region of Italy.
      Comparison of the patients treated with PE and IVIg showed no significant
      differences in terms of effectiveness in improving the clinical course of GBS: at
      one month, respectively 11.1% and 25% had recovered, and 55.5% and 58.3% had
      improved by at least one grade. These results are in agreement with those of the
      Dutch GBS trial. No relapses were observed in either group. Moreover, our results
      showed no difference in clinical outcome at 1 and 3 months between the patients
      receiving only one therapy and those receiving two; a second cycle of therapy did
      not seem to improve the clinical course of the disease significantly. We conclude
      that PE and IVIg are both safe and effective therapies for GBS.

PMID- 8749708
TI  - Brain metastases from post-radiation malignant peripheral nerve sheath tumour.
AB  - A 45-year-old female patient developed a malignant peripheral nerve sheath tumour
      (MPNST) arising from the left brachial plexus, ten years after regional radiation
      treatment for Hodgkin's disease. The clinical course was characterized by local
      recurrence, pulmonary and cerebral metastases with endocranic hypertension
      syndrome, and the death of the patient 18 months after the onset of symptoms. The
      tumour presented a histopathological picture of schwannoma with a high grade of
      malignancy. A particular feature of this case was the exceptional occurrence of
      the early and massive invasion of the brain.

PMID- 8749709
TI  - Cock-crow reflex epilepsy.

PMID- 8749710
TI  - Absence of brainstem reflexes with intact Vth and VIIth nerves in Shy Drager
      syndrome.

PMID- 8749711
TI  - Properties and regulation of 17 beta-hydroxysteroid oxidoreductase of OVCAR-3,
      CAOV-3, and A431 cells: effects of epidermal growth factor, estradiol, and
      progesterone.
AB  - Although there is a growing body of evidence that 17 beta-hydroxysteroid
      oxidoreductase plays a role in the regulation of steroid levels in epithelial
      tumors of the endometrium and breast, our knowledge of its role in other
      gynecologic tumors is limited. In this investigation, the 17 beta-hydroxysteroid
      oxidoreductase activity of cell lines derived from two ovarian tumors (OVCAR-3,
      CAOV-3) and an epidermoid tumor of the vulva (A431) was assayed under conditions
      which differentiate between 17 beta-hydroxysteroid oxidoreductase type 1, a
      cytosolic isoform highly specific for estradiol, and type 2, a membrane bound
      isoform reactive with both estradiol and testosterone. On the basis of
      estradiol/testosterone activity ratios, all three cell lines appear to have type
      2-like activity, with the specific activity of A431 markedly greater than that of
      the other cell lines. Estradiol, progesterone, or EGF, alone or in combination,
      were without effect on the enzymatic activity of OVCAR-3 cells. EGF decreased the
      activity of CAOV-3 cells slightly. In contrast, EGF stimulated A431 17 beta
      hydroxysteroid oxidoreductase activity 7-8-fold over a 5-day exposure. Estradiol
      or progesterone, singly or in combination, also did not effect the enzymatic
      activity of A431 cells. However, progesterone inhibited the increase in activity
      seen in the presence of EGF. With EGF, estradiol, and progesterone together, the
      increase in enzymatic activity was comparable to that with EGF alone. The effects
      of estradiol and progesterone appear to result from steroid actions following
      binding of EGF to low-affinity receptors on A431 cells.

PMID- 8749712
TI  - Molecular cloning of a mouse epithelial protein-tyrosine phosphatase with
      similarities to submembranous proteins.
AB  - Protein-tyrosine phosphatases (PTPases) form an important class of cell
      regulatory proteins. We have isolated overlapping cDNA clones that together
      comprise an 8 kb transcript encoding a novel murine PTPase which is expressed in
      various organs. Sequence analysis revealed an open reading frame of 2,460 amino
      acid residues. The predicted protein, PTP-BL, is a large non-transmembrane PTPase
      that exhibits 80% homology with PTP-BAS, a recently described human PTPase. PTP
      BL shares some intriguing sequence homologies with submembranous proteins. It
      contains a band 4.1-like motif also present in the tumor suppressors
      neurofibromatosis 2 and expanded, five 80 amino acid repeats also present in the
      discs-large tumor suppressor, and a single catalytic phosphatase domain. No
      obvious homologies to other proteins were found for the N-terminal region of the
      protein other than human PTP-BAS. RNA in situ hybridization experiments show that
      the PTP-BL gene is expressed in epithelial cells, predominantly in kidney, lung,
      and skin. These data suggest a cell cortical localization for PTP-BL in
      epithelial cells and a possible role in the morphology and motility of epithelial
      tissues.

PMID- 8749713
TI  - Molecular cloning of a novel myeloid granule protein.
AB  - Granulocytes are recognized by the presence of granules, including primary
      (azurophilic) and secondary types. Each granule type contains distinct and
      characteristic families of enzymes. We have screened a murine bone marrow cDNA
      library to obtain a series of sequences corresponding to mRNAs which are both
      myeloid-specific and appear to be expressed only in immature bone marrow cells. A
      1,160 bp sequence (B9) has been isolated, which shows restricted expression in
      murine bone marrow, with the highest levels in cultures enriched for
      promyelocytes. Translation yields a single open reading frame of 167 amino acids
      and a calculated MW of 19.33 kd. A single potential N-glycosylation site is
      present. Evaluation of the amino terminal sequence shows 2 polar amino acids
      flanking a hydrophobic region, suggesting a signal sequence and the possibility
      of post-translational modification. An extensive search of the protein data base
      reveals 30% identity over 90 amino acids with porcine cathelin, a cystatin-like
      cysteine proteinase inhibitor. This sequence identity includes conservation of
      the 4 cysteine residues noted in all members of the cystatin superfamily. In an
      attempt to further characterize this novel sequence, a polyclonal antiserum was
      prepared by immunization with a 20 amino acid synthetic peptide corresponding to
      a unique portion of the carboxy terminus. Immunoelectron microscopy localized B9
      to neutrophilic granules. We have identified a novel myeloid-specific granule
      protein related to porcine cathelin, but showing important structural
      differences. This may represent the first isolated member of a new cystatin
      family. More importantly, the small size of the B9 gene and its tight pattern of
      early expression make B9 an excellent reporter molecule for the study of new
      factors important in myeloid differentiation.

PMID- 8749714
TI  - Phosphorylation of eIF-4E and initiation of protein synthesis in P19 embryonal
      carcinoma cells.
AB  - Mitogenic stimulation of protein synthesis is accompanied by an increase in eIF
      4E phosphorylation. The effect on protein synthesis by induction of
      differentiation is less well known. We treated P19 embryonal carcinoma cells with
      the differentiating agent retinoic acid and found that protein synthesis
      increased during the first hour of addition. However, the phosphorylation state,
      as well as the turnover of phosphate on eIF-4E, remained unchanged. Apparently,
      the change in protein synthesis after RA addition is regulated by another
      mechanism than eIF-4E phosphorylation. By using P19 cells overexpressing the EGF
      receptor, we show that the signal transduction pathway that leads to
      phosphorylation of eIF-4E is present in P19 cells; the EGF-induced change in
      phosphorylation of eIF-4E in these cells is likely to be regulated by a change in
      eIF-4E phosphatase activity. These results suggest that the onset of retinoic
      acid-induced differentiation is triggered by a signal transduction pathway which
      involves changes in protein synthesis, but not eIF-4E phosphorylation.

PMID- 8749715
TI  - Cyclic-AMP deficient MDCK cells form tubules.
AB  - It has been known for many years that MDCK cells form blister-like structures,
      termed domes. During an examination of the morphology of a large number of MDCK
      clones, we found that two stable morphotypes exist in an MDCK cell population
      namely, dome-forming and tubule-forming clones. When maintained at high cell
      density, tubule-forming clones displayed large numbers of anastomosing tubules
      which contained lumens. The frequency of observation of the tubule-forming clones
      in an MDCK population was 0.7%. Tubule-forming MDCK clones should be useful in
      studying tubule morphogenesis. While agents that affect protein kinase A activity
      increased dome formation, the same agents abolished the formation of tubules in
      all tubule-forming clones. In contrast, drugs that stimulate protein kinase C
      activity (phorbol esters and staurosporine) decreased dome formation an increased
      tubule morphogenesis in all MDCK morphotypes. Tubule-forming clones were found to
      have lower resting levels of cyclic-AMP and to respond to forskolin stimulation
      of adenylate cyclase less readily. Hence, signals transmitted by the protein
      kinase C pathway appear to lead to tubule formation in MDCK cells, while signals
      transmitted through the protein kinase A pathway lead to dome formation.

PMID- 8749716
TI  - Conditional gene expression in secretory tissues and skin of transgenic mice
      using the MMTV-LTR and the tetracycline responsive system.
AB  - Molecular mechanisms of development and disease can be studied in transgenic
      animals. Controlling the spatial and temporal expression patterns of transgenes,
      however, is a prerequisite for the elucidation of gene function in the whole
      organism. Previously we reported that mice carrying a tetR/VP16 hybrid gene
      (tTA), under the control of the human cytomegalovirus immediate early 1 (HCMV
      IE1) gene promoter, can be used to temporally activate the expression of
      transgenes under the control of a promoter containing tetop sequences. We now
      show that the MMTV-LTR can be used to target expression of tTA to the epithelial
      cells of secretory organs and skin in transgenic mice. Notably, nearly uniform
      expression of a tetop-lacZ transgene was found in seminal vesicle, salivary
      gland, and Leydig cells of mice carrying also the MMTV-tTA transgene. More
      heterogeneous patterns of gene expression were observed in mammary epithelial
      cells and basal cells of the epidermis. Different MMTV-tTA lines had comparable
      tissue expression patterns. Transcriptional activation mediated by tTA was up to
      several hundredfold, and it was abrogated after the administration of
      tetracycline. The MMTV-tTA mice established in this work will be useful for
      experiments examining the roles of biological factors at defined developmental
      stages in the epithelial cells of salivary gland, seminal vesicle, mammary gland,
      and skin and the Leydig cells of testes. In addition, in combination with the
      CRE/lox recombination system, these mice wil be useful to achieve gene deletions
      at defined time points in these organs.

PMID- 8749717
TI  - U2 and U1 snRNA gene loci associate with coiled bodies.
AB  - The coiled bodies are nuclear structures rich in a variety of nuclear and
      nucleolar components including snRNAs. We have investigated the possibility that
      coiled bodies may associate with snRNA genes and report here that there is a high
      degree of association between U2 and U1 genes with a subset of coiled bodies. As
      investigated in human HeLa cells grown in monolayer culture, about 75% of nuclei
      had at least one U2 gene associated with a coiled body, and 45% had at least one
      U1 locus associated. In another suspension-grown HeLa cell strain, 92% of cells
      showed associated of one or more U2 genes with coiled bodies. In contrast to the
      U2 and U1 gene associations, a locus closely linked to the U2 gene cluster
      appeared associated with a coiled body only in 10% of cells. Associated snRNA
      gene signals were repeatedly positioned at the edge of the coiled body. Thus,
      this associated was highly nonrandom and spatially precise. Our analysis revealed
      a much higher frequency of association for closely spaced "doublet" U2 gene
      signals, with over 80% of paired signals associated as opposed to 35% for single
      U2 signals. This finding, coupled with the fact that not all genes were
      associated in all cells, suggested the possibility of a cell-cycle-dependent,
      possibly S-phase, association. However, an analysis of S- and non-S-phase cells
      using BrdU incorporation or cell synchronization did not indicate an increased
      level of association in S-phase. These and other results suggested that a
      substantial fraction of paired U2 signals represented association of U2 genes on
      homologous chromosomes rather than only replicated DNA. Furthermore, triple label
      analysis showed that in a significant fraction of cells U1 and U2 genes were both
      associated with the same coiled body. U1 and U2 genes were closely paired in
      approximately 20% of cells, over 60% of which were associated with a readily
      identifiable coiled body. This finding raises the possibility that multiple genes
      of a particular class may be in association with each coiled body. Thus, the
      coiled body may be a dynamic structure which transiently interacts with or is
      formed by one or more specific genetic loci, possibly carrying out some function
      related to their expression.

PMID- 8749718
TI  - rHox: a homeobox gene expressed in osteoblastic cells.
AB  - Homeodomain proteins are characterized by a conserved domain with a helix-turn
      helix motif. These proteins act as regulatory factors in tissue differentiation
      and proliferation. However, their role in the regulation of osteoblast
      differentiation is unknown. In this study we have identified and characterized a
      homeobox gene in osteoblast-like cells. This gene, termed rHox, was isolated from
      a cDNA library derived from rat osteoblast-like cells. The nucleotide sequence of
      the 1,375 base pair (bp) cDNA contains a noncoding leader sequence of 329 bp, a
      735 bp open reading frame, and 312 bp of 3' noncoding sequence. Sequence
      comparison demonstrates that rHox is identical to the mouse Pmx gene (also called
      MHox) at the amino acid level and 90% homologous at the nucleotide level. Both
      Southwestern blotting and gel shift analyses indicate that rHox has potential to
      bind both the collagen I alpha 1 and the osteocalcin promoters. Transfection
      experiments using an rHox expression vector showed a strong repression of target
      promoter activity, regardless of whether the target promoters contained
      homeodomain binding response elements. These data suggest that rHox is a potent
      negative regulator of gene expression, although the specific role of rHox in bone
      gene regulation remains to be determined.

PMID- 8749719
TI  - Nuclear domain 10 (ND10) associated proteins are also present in nuclear bodies
      and redistribute to hundreds of nuclear sites after stress.
AB  - The promyelocytic leukemia protein fused to the retinoic acid receptor alpha in
      t(15;17) acute promyelocytic leukemia, the primary biliary cirrhosis autoantigen,
      Sp100, as well as the incompletely characterized protein NDP55, are co-localized
      in specific immunohistochemically defined nuclear domains (ND10), which are
      potential equivalents of ultrastructurally defined nuclear bodies. We
      investigated whether the distribution of these proteins depends on environmental
      conditions and whether ND10 correlate with nuclear bodies. Certain nuclear bodies
      and ND10 react in a similar way and share antigens. Interferon exposure doubled
      the number of ND10 and increased the frequency of nuclear bodies, whereas herpes
      simplex virus infection or heat shock modify both. Redistribution of ND10
      associated proteins to hundreds of small sites throughout the chromatin was
      inducible by stress in the form of heat shock and exposure to Cd++ ions. The
      change of distribution was rapid and independent of protein synthesis, and thus
      not part of the classical heat shock response. The very rapid redistribution of
      these proteins after heat shock, together with the development of ND10 upon
      interferon activation, raises the possibility that ND10 represent storage sites
      of certain matrix proteins readily accessible throughout the chromatin in
      response to stress or other effectors that induce global nuclear changes.

PMID- 8749720
TI  - Prothrombin cleavage by human vascular smooth muscle cells: a potential
      alternative pathway to the coagulation cascade.
AB  - Thrombin is a potent mitogen for human vascular smooth muscle cells (HVSMC) and
      its enzymatic activity is required for this function. The present study
      demonstrates that prothrombin is also mitogenic for HVSMC due to the generation
      of enzymatically active thrombin which occurs upon incubation of prothrombin with
      the cells. Analysis by SDS-PAGE, immunoblotting, and amino acid sequencing
      revealed that prothrombin incubated with HVSMC undergoes limited proteolysis.
      Prethrombin 1 was formed through cleavage at R155-S156. Cleavage at R271-T272
      generated fragment 1.2 and prethrombin 2 whilst cleavage at R284-T285 yielded
      truncated prothrombin 2 (prethrombin 2'). However, cleavage at R320-I321 which,
      during prothrombin activation produces two-chain alpha-thrombin, was not
      detectable. Studies on HVSMC-conditioned medium revealed that a similar pattern
      of prothrombin cleavage occurred by a cell-secreted factor(s). Amidolytic
      activity analysis indicated that 1-3% catalytically active thrombin-like activity
      was generated upon incubation of prothrombin with HVSMC-conditioned medium. By
      treating conditioned medium with various classes of proteinase inhibitors or
      hirudin, it was determined that prothrombin is cleaved by a cell-derived serine
      proteinase-like factor(s) at R271-S272 and by alpha-thrombin at R155-S156 and
      R284-T285. Antibodies neutralising the activity of either urokinase, tissue
      plasminogen activator, or factor Xa failed to alter the prothrombin cleaving
      activity of conditioned medium. This activity which may catalyse an alternative
      pathway for the generation of thrombin, was eluted from a gel filtration column
      as a single peak with apparent molecular mass of 30-40 kDa.

PMID- 8749721
TI  - Human myeloid cell nuclear differentiation antigen binds specifically to
      nucleolin.
AB  - The human myeloid cell nuclear differentiation antigen (MNDA) is a nuclear
      protein expressed specifically in cells of the myelomonocytic lineage and
      regulated by interferon alpha in a cell-specific fashion. MNDA is also a member
      of a family of interferon-regulated genes of unknown function. In an effort to
      elucidate the function of MNDA, three techniques (affinity purification,
      coimmunoprecipitation, and protein blot assay) were used to characterize its
      specific protein binding activities. Microsequence analysis showed that MNDA
      bound the 100 kDa nucleolin protein. The identification of nucleolin was
      confirmed by immunoreaction with specific antibodies. MNDA contains motifs which
      could account for specific binding to nucleolin. Nucleolin binds other
      macromolecules and exhibits features consistent with roles in signal
      transduction, production of ribosomes, nuclear matrix structure, and regulation
      of transcription. The present results indicate that the function of MNDA is most
      likely related to interactions with other proteins. Through these associations,
      MNDA could contribute cell/lineage- and differentiation-specific limits to the
      function of ubiquitous proteins such as nucleolin. Further analysis of MNDA
      protein binding could be critical to elucidating the function of MNDA and could
      contribute to understanding the function of the products of other members of this
      interferon-inducible family of genes.

PMID- 8749722
TI  - Retrovirally mediated wild-type p53 restores S-phase modulation without inducing
      WAF1 mRNA in breast carcinoma cells containing mutant p53.
AB  - The mechanism of negative growth regulation by the nuclear phosphoprotein p53 in
      breast cancer cells may rely on its role as a transcriptional activator of cell
      cycle-related genes. We have tested this hypothesis using retrovirally transduced
      wild-type (wt) p53 in breast cancer cell lines containing homozygously endogenous
      mutant (mt) p53. Restoring the expression of wt p53, the percentage of cells in S
      phase was reduced, G1/S transition was slowed, and progression through S was
      restrained. The fraction of cells with a flattened "Cdk-minus" phenotype
      increased 5- to 10-fold. High constitutive mRNA expression of the cyclin-Cdk
      inhibitor WAF1 in MDAMB231 cells was not induced upon restored wt p53 expression
      suggesting a p53-independent pathway in the regulation of WAF1 mRNA expression.
      Wt p53 acted trans-dominantly in the presence of accumulating mt p53 and
      installed a modulation of G1/S transition and S phase progression independent of
      WAF1 expression.

PMID- 8749723
TI  - Financing strategies for drug abuse treatment programs.
AB  - Contemporary drug abuse treatment programs exist in an extremely complex
      financing environment. Programs face a myriad of funding sources with different
      eligibility requirements and payment mechanisms that make it difficult for
      programs to develop a single financing strategy. To complicate the financing
      process, current funding sources are in a state of flux as managed care gains
      significance in health care reimbursement. This article will assist drug abuse
      treatment programs in several ways. First, it summarizes information about
      funding, eligibility requirements and payment mechanisms. Second, the information
      is geared toward drug treatment programs and less toward policymakers. Third, the
      article describes strategies for obtaining funding, including strategies for
      interacting with managed care. By using these methods for obtaining revenues, it
      is hoped that drug treatment programs will be able to increase their financing
      effectiveness.

PMID- 8749724
TI  - Effectiveness of adjunct therapies in crack cocaine treatment.
AB  - Although intensive outpatient therapy is recommended for treatment of cocaine,
      psychosocial characteristics associated with crack cocaine abuse are also
      implicated in attrition from outpatient programs. Acupuncture, medications, and
      brainwave therapy (biofeedback), have all been used to encourage treatment
      retention and drug use outcomes. The effectiveness of three adjunct therapies in
      improving retention and drug use outcomes in intensive outpatient cocaine
      treatment was tested in a primarily young, indigent African-American sample of
      crack cocaine users at a community hospital in a low-income, high drug use
      neighborhood in Houston. Subjects were assigned to receive either neurobehavioral
      treatment alone or neurobehavioral with one of three adjunct therapies. These
      included acupuncture, anticraving medication, or brainwave therapy. Comparative
      results indicated that dosage of any adjunct therapy was associated with days in
      treatment and standard treatment sessions attended, and that standard treatment
      sessions attended was associated with negative urinalysis results at follow-up.
      None of the adjunct therapies were directly associated with drug use outcomes.

PMID- 8749725
TI  - A model for pharmacological research-treatment of cocaine dependence.
AB  - Major problems for research on pharmacological treatments for cocaine dependence
      are lack of comparability of results from different treatment research programs
      and poor validity and/or reliability of results. Double-blind, placebo
      controlled, random assignment, experimental designs, using standard intake and
      assessment procedures help to reduce these problems. Cessation or reduction of
      drug use and/or craving, retention in treatment, and medical and psychosocial
      improvement are some of the outcome variables collected in treatment research
      programs. A model to be followed across different outpatient clinical trials for
      pharmacological treatment of cocaine dependence is presented here. This model
      represents an effort to standardize data collection to make results more valid
      and comparable.

PMID- 8749726
TI  - Desipramine, amantadine, or fluoxetine in buprenorphine-maintained cocaine users.
AB  - The clinical efficacy of promising cocaine anti-craving medications was examined
      in combination with buprenorphine. Twenty-one opioid-dependent cocaine abusers
      were enrolled in a double-blind, 12-week trial in which they received on a daily
      basis buprenorphine (8 mg, s.l.) plus either desipramine (150 mg, p.o.),
      amantadine (300 mg, p.o.), or fluoxetine (60 mg, p.o.). Urine samples and self
      reported drug use were obtained 1-3 times/week. The order of greatest patient
      retention across the 12 weeks was desipramine (83.3%) > amantadine (66.7%) >
      fluoxetine (20.0%). The desipramine and amantadine groups appeared to have
      greater increases in opioid- and cocaine-free urines than the fluoxetine group.
      These results suggest that desipramine and amantadine may facilitate greater
      opioid and cocaine abstinence than fluoxetine.

PMID- 8749727
TI  - Key ingredients to effective addictions treatment.
AB  - Based on previous reviews and recent empirical findings a number of assertions
      can be made as to what constitutes the active ingredients for the effective
      treatment of addictive disorders. These key ingredients include the following:
      easy accessibility of care, treatment flexibility, the involvement of
      collaterals, good therapists, motivated clients, matching treatment to salient
      client variables, client accountability for their sobriety, focused treatment
      approaches, and the follow-up of drop-outs and program graduates. A program
      developed based on these key ingredients showed a 64% abstinence rate among
      clients in the Action stage of recovery and a 56% abstinence rate for clients in
      the Contemplation stage. It is proposed that these key ingredients are generic to
      all effective substance abuse treatment programs and apply at both a programmatic
      level and an individual practitioner level.

PMID- 8749728
TI  - A day treatment program in a therapeutic community setting: six-month outcomes.
      The Walden House Day Treatment Program.
AB  - Although not well represented in the literature, day treatment programs targeting
      substance abuse problems have increased in both number and acceptability in
      recent years. This article reports on a day treatment program based on the
      Therapeutic Community (TC), and on outcomes for a sample of substance abuse
      clients (n = 66) entering the program. Participants were interviewed early in
      treatment and 6 months after admission using the Addiction Severity Index (ASI)
      and other measures. Clients entering day treatment were demographically diverse,
      with serious substance-abuse problems and psychiatric morbidity. Median retention
      in day treatment was about 5 weeks, but many clients received a contiguous
      episode of residential treatment, so that the median for total time in treatment
      was 18 weeks. Clients located and interviewed at 6-month follow-up (n = 38)
      showed significant improvement in alcohol and drug use, legal and social
      problems, and psychiatric symptoms. Findings suggest that day treatment can be
      used effectively as a precursor to residential treatment and that some clients
      applying for residential treatment can be treated effectively in day treatment
      alone.

PMID- 8749729
TI  - Treatment of alcohol and cocaine addiction by the combination of pemoline and
      fenfluramine: a preliminary case series.

PMID- 8749730
TI  - Quantification of metabolites from single-voxel in vivo 1H NMR data of normal
      human brain by means of time-domain data analysis.
AB  - We present here a combination of time-domain signal analysis procedures for
      quantification of human brain in vivo 1H NMR spectroscopy (MRS) data. The method
      is based on a separate removal of a residual water resonance followed by a
      frequency-selective time-domain line-shape fitting analysis of metabolite
      signals. Calculation of absolute metabolite concentrations was based on the
      internal water concentration as a reference. The estimated average metabolite
      concentrations acquired from six regions of normal human brain with a single
      voxel spin-echo technique for the N-acetylaspartate, creatine, and choline
      containing compounds were 11.4 +/- 1.0, 6.5 +/- 0.5, and 1.7 +/- 0.2 mumol kg-1
      wet weight, respectively. The time-domain analyses of in vivo 1H MRS data from
      different brain regions with their specific characteristics demonstrate a case in
      which the use of frequency-domain methods pose serious difficulties.

PMID- 8749731
TI  - In vivo localized 1H spectroscopy of the rat eye at 7 T: preliminary studies.
AB  - Preliminary in vivo proton spectroscopic studies of the posterior chamber of the
      rat eye have been undertaken at 7 T. The Spatial and Chemical shift encoded
      Excitation (SPACE) localization sequence was used to acquire signals from 10
      microliter voxels and demonstrate the presence of metabolites associated with the
      vitreous humor, lens, retina, and the optic nerve. Localized T2 and T1
      measurements of water in the vitreous humor indicate a relatively fluid
      environment. Susceptibility maps are used to demonstrate the difficulties of in
      vivo spectroscopic investigations in the anterior regions of the eye. Comments
      are made concerning the implications for spectral resolution in these regions.

PMID- 8749732
TI  - MR imaging of focal liver lesions: comparison between turbo spin-echo and
      conventional spin-echo pulse sequences.
AB  - The aim of this study was to compare conventional spin-echo (CSE) T2-weighted
      (T2W) images with turbo spin-echo (TSE) T2W pulse sequences in their ability to
      detect focal liver lesions. Seventy-eight consecutive patients with focal liver
      lesions were entered into this study. All patients were imaged using the gradient
      echo (GE) sequence with the breath-hold technique for T1-weighted (T1W) images,
      and CSE and TSE sequences for T2W images. Qualitative evaluation included lesion
      detection (number of lesions detected) and conspicuity (extent of visualization
      of lesional borders); quantitative evaluation included the signal-to-noise (S/N)
      ratio and the contrast-to-noise (C/N) ratio. TSE showed the best performance in
      terms of lesion detection; however, the difference between TSE and CSE was
      significant only in the case of benign cysts (p < 0.01). Conspicuity was higher
      with TSE and CSE, and lower with GE. The S/N and C/N ratios of the two T2W
      sequences were also comparable, and better than those of GE. However, the
      combined use of GE and TSE resulted in improved lesion detection. The results
      show that, because the acquisition time is greatly reduced with TSE sequences,
      these should be considered as first-line approach to magnetic resonance imaging
      of the liver for the study of focal lesions.

PMID- 8749733
TI  - Breath-hold spin-echo MR imaging for evaluation of dynamic enhancement of native
      and treated hepatocellular carcinoma after intravenous Gd-DTPA administration.
AB  - Using a simple modification of a standard spin-echo sequence which enable
      acquisition of three breath-hold images in 15 s, dynamic enhancement of 30
      histologically proven hepatocellular carcinomas (17 native tumors, 6 completely
      necrotic tumors after nonsurgical treatments, and 7 tumors with viable and
      necrotic portions) after intravenous injection of gadolinium-DTPA was evaluated.
      Native hepatocellular carcinomas and viable portions in treated nodules showed
      elective enhancement in images obtained 40 s after contrast injection. Contrast
      between these lesions and the normal liver decreased thereafter. No contrast
      uptake was seen in entirely necrotic nodules and necrotic portions of treated
      nodules. Because of the capability to demonstrate the elective arterial blood
      supply typical of hepatocellular carcinoma, breath-hold T1-weighted spin-echo
      sequence should replace conventional T1-weighted images for the evaluation of
      intravenously administered gadolinium-DTPA enhancement of this tumor before and
      after nonsurgical treatments.

PMID- 8749734
TI  - Evaluation of five protocols for quantification of two-dimensional MR
      spectroscopic images.
AB  - Five protocols were tested for quantification on in vivo two-dimensional
      spectroscopic imaging datasets. The datasets are duplo measurements from three
      individuals. The peaks for N-acetyl aspartate, creatines, and cholines were
      quantified. The first of the protocols is conventional integration of a selected
      interval around the peak. The others are various implementations of a Gauss
      Newton-based least-squares time-domain fitting algorithm. Fitting a half-echo
      (free-induction decay curve, FID) to a full echo was compared; this was combined
      with or without filtering out the water signal using the Lanczos-Hankel singular
      value decomposition (LHSVD). It appears that conventional integration yields
      consistent and accurate results in comparison to the fitting methods. The
      combination of LHSVD and echo fitting performs equally well; advantages and
      disadvantages are discussed. The protocols using FID fitting perform poorly with
      these experimental datasets.

PMID- 8749735
TI  - An efficient birdcage resonator at 2.5 MHz using a novel multilayer self
      capacitance construction technique.
AB  - The birdcage resonator, well appreciated for its high signal-to-noise ratio and
      its magnetic field uniformity characteristics, operates efficiently in mid- to
      high-field MRI systems but, unfortunately not for low-field (< 0.4 T)
      applications. The inherently low inductance of the birdcage architecture is the
      main obstacle to achieving low-frequency resonance because of the need to use
      very high-value capacitors for the tuning. Small-case-size, high-value ceramic
      capacitors are known to have high dissipation factors which when used in the
      fabrication of RF coils could result in poor efficiency. To overcome this
      limitation, a novel technique known as multilayer self-capacitance (MLSC)
      construction has been developed and a prototype 2.5 MHz bird-cage resonator of
      length 25 cm and diameter 20 cm has been built. The technique involves the
      modification of the leg sections of the conductors constituting the bird cage
      into integrated capacitors using very low-loss materials as dielectrics. The
      observed unloaded Q-factor was 267 using the MLSC construction, and when loaded
      with a 16-cm-diameter bottle of 0.45% saline, its Q dropped to 246. The RF field
      uniformity plots have demonstrated that the MLSC technique has no adverse effects
      on the magnetic field homogeneity of the bird-cage resonator.

PMID- 8749736
TI  - Susceptibility-based MRI contrast of the CSF by intravascular superparamagnetic
      nanoparticles.
AB  - Endorem, a suspension of superparamagnetic iron oxide dextran nanoparticles (NP),
      have been injected intravenously to healthy anesthetized rats for the purpose of
      contrast enhancement of brain in gradient-echo imaging at 200 MHz. Not only gray
      and white matter but also particular regions of the cerebrospinal fluid (CSF)
      were contrasted in sagittal and transverse images, although samples of this fluid
      did not contain NP. The selected contrast in the CSF would result form the
      ability of dense vascular beds containing highly magnetized particles to induce a
      remote susceptibility effect far beyond the vascular walls into a large fraction
      of extravascular water.

PMID- 8749737
TI  - Multiple chemical sensitivity syndrome.

PMID- 8749738
TI  - Occupational electric and magnetic field exposure and brain cancer: a meta
      analysis.
AB  - We conducted a meta-analysis to acquire an understanding of the association
      between central nervous system cancer and occupational exposure to electric and
      magnetic fields. To explore sources of heterogeneity, study characteristics were
      scored and examined using regression analysis. An inverse-variance weighted
      pooling leads to a small overall increase in relative risk (10 to 20%) for the
      broad group of electrical occupations. One of the largest differences was lower
      relative risk for Scandinavian studies. Lower relative risks were also reported
      in cohort- and incidence-based studies. Findings were not sensitive to
      assumptions, including unpublished data, influence of individual studies,
      weighting schemes, and modeling. Whereas most studies present a small elevation
      in risk, there is considerable heterogeneity among the results.

PMID- 8749739
TI  - Silicosis and workers' compensation in New Jersey.
AB  - The employer is expected to maintain responsibility for health care expenses and
      lost income that result from occupational injury and illness through the workers'
      compensation insurance system. However, financial support for individuals with
      occupational illnesses, especially those with long latency, is often from sources
      other than workers' compensation. Silicosis, a well defined, chronic,
      occupational lung disease, can be viewed as a sentinel for the inadequacy of the
      public policy to compensate workers for chronic occupational lung disease. Three
      hundred twenty-nine patients with confirmed silicosis were identified by the
      silicosis surveillance program in the New Jersey Department of Health using
      source data from 1979 through 1992. One hundred seventy-seven of these
      individuals provided information on the status of any compensation claims against
      their employer. Only 31% of these patients stated that a claim had been filed;
      84% of those whose claims were settled were awarded payments. Severity of
      radiologic findings was not associated with the likelihood of filing a claim or
      with being awarded a payment; whereas, smoking was associated with these
      outcomes. The implications of these findings for the health care system are
      discussed.

PMID- 8749740
TI  - Occupational mortality among firefighters: assessing the association.
AB  - Because of their occupational exposure to a variety of toxic agents, fire
      fighters may be at risk for a number of exposure-related diseases. We reviewed
      the current literature on disease risk among fire fighters to compare findings
      and to infer magnitude of risk. A standard mortality ratio (SMR) of 200 is equal
      to an attributable risk of 100% of expected, sufficient to justify presumption in
      most workers' compensation systems that accept this. We therefore concentrated on
      risks that approach or exceed an SMR of 200 or an equivalent risk estimate,
      bearing in mind that confidence intervals around these estimates are wide. Based
      on the criteria for presumption of occupational risk, we suggest the following
      conclusions with respect to general presumption of risk: (1) Lung cancer: There
      is evidence for an association but not of sufficient magnitude for a general
      presumption of risk. (2) Cardiovascular. There is no evidence for an increased
      risk of death overall from heart disease. Sudden death, myocardial infarction, or
      fatal arrhythmia occurring on or soon after near-maximal stress on the job are
      likely to be heart related, but such "heart attacks" occurring away from work
      cannot be presumed to be work related. (3) Aortic aneurysm: The evidence is
      incomplete for an association, but if an association does exist, it would
      probably be of a magnitude compatible with a general presumption of risk. (4)
      Cancers of the genitourinary tract, including kidney, ureter, and bladder: The
      evidence is strong for both an association and for a general presumption of risk.
      (5) Cancer of brain: Incomplete evidence strongly suggests a possible association
      at a magnitude consistent with a general presumption of risk. (6) Cancer of
      lymphatic and hematopoietic tissue: By group, there is some evidence for both an
      association and a general presumption or risk. However, the aggregation is
      medically meaningless. We therefore recommend a case-by-case approach. (7) Cancer
      of the colon and rectum: There is sufficient evidence to conclude that there is
      an association but not that there is a general presumption of risk. (8) Acute
      lung disease: Unusual exposures, such as exposure to the fumes of burning
      plastics, can cause severe lung toxicity and even permanent disability. This does
      not appear to result in an increased lifetime risk of dying from chronic lung
      disease.

PMID- 8749741
TI  - Contrast sensitivity in organic-solvent-induced chronic toxic encephalopathy.
AB  - This is a study of visual contrast sensitivity in a series of subjects with
      previously diagnosed occupational organic-solvent-induced chronic toxic
      encephalopathy. Contrast sensitivity was measured for 16 subjects using the
      Vistech VCTS 6500 chart. The results were compared with age-stratified normal
      data. Six of the 16 subjects (37.5%) recorded abnormal contrast sensitivity
      results. Monocular abnormalities were found for two (33%) of these subjects.
      Statistically significant abnormalities in contrast sensitivity were observed at
      the intermediate spatial frequencies of three cycles per degree (cpd; P < .0005),
      6 cpd (P < .025), and 12 cpd (P < .01). We conclude that contrast sensitivity is
      abnormal in some cases of occupational organic-solvent-induced chronic toxic
      encephalopathy. Intermediate spatial frequency channel neurones in the visual
      system may be more vulnerable to solvent toxicity than those of low or high
      spatial frequency. Contrast sensitivity testing may be a useful adjunct in the
      diagnostic process for this disease. Further research involving larger numbers of
      subjects is recommended.

PMID- 8749742
TI  - The lack of causality between asbestos and colorectal cancer.
AB  - To evaluate a potential causal relationship between asbestos exposure and the
      risk of colorectal cancer, 30 cohort studies published in English were reviewed
      and analyzed. The latest report of each cohort up through 1993 was used. The
      outcome measure was the standardized morbidity (incidence) or mortality ratio
      (SMR). Summary SMRs were examined by type of cohort registration, type of work,
      type of asbestos, latency from onset of exposure to period of risk, and incidence
      only. The overall relative risk was 0.99 for all 30 studies. The evidence does
      not meet the important criteria for a judgment of causality because the relative
      risk is not consistently elevated, weak in the two studies with a statistically
      significant elevation of SMR, and limited data do not support a dose-response
      relationship.

PMID- 8749743
TI  - Occupational injuries in a poor inner-city population.
AB  - This study aims to characterize occupational injuries in a defined poor inner
      city population in terms of demographic features, types, and circumstances of
      injuries, and medical and financial consequences. It is a case series drawn from
      a larger population-based injury registry in emergency departments that serve 17
      poor census tracts in Philadelphia. Of 335 patients from the study area who had
      been treated at the emergency departments under study for occupational injuries,
      107 could be contacted by telephone 2 to 3 years after their injuries. Interviews
      sought information on the patients, their employment, their injuries, and the
      consequences. Respondents were almost all African-American, approximately 50%
      male, and had a median age of 32. Approximately one third were employed in the
      health care industry, one fourth in the service sector (including conventional
      service firms, restaurants, and hotels), and the remainder in construction,
      retail and wholesale trade, education, transportation, and manufacturing. Major
      causes of injuries included overexertion, contact with sharp objects, and falls.
      Major types on injuries included sprain/strains and lacerations. Approximately
      half the respondents had missed more than 3 days of work, with 15% missing more
      than 1 month. Almost 40% of respondents reported persistent health problems after
      their injuries. Only about one quarter had received workers' compensation. We
      conclude that poor and minority workers are at risk of a wide range of
      occupational injuries, which may result in considerable lost work time and have
      serious medical and economic consequences. More, attention to the workplace risks
      of these relatively marginalized workers and more vigorous preventive
      interventions are needed.

PMID- 8749744
TI  - Total hip and knee replacement treatment programs: a report using consensus.
AB  - Physical therapists may use varied treatment protocols for the acute care of
      patients with to hip or knee replacements. The purpose of this study was to
      develop, via consensus, a standardized treatment program for patients receiving
      total hip or knee replacement for primary osteoarthritis. Eighteen clinicians
      nationwide participated in a three-round consensus process. In Round 1, over 80%
      of the panel identified exercise, transfers, ambulation, and discharge criteria
      as the important treatment categories. In Round 2, they reviewed the preliminary
      physical therapy treatment program and recommended additional exercise regimes.
      In Round 3, 76% of the panel accepted the final total hip replacement program
      while 70% of the panel accepted the total knee replacement program. Using the
      consensus development process, physical therapists may begin to define their
      treatment programs which is fundamental to establishing a baseline standard of
      care.

PMID- 8749745
TI  - Balance abilities of professional dancers on select balance tests.
AB  - Documentation that dancers have better balance abilities than nondancers is
      important because of the number of dancers who sustain injury and then are
      referred to physical therapists for treatment. The purpose of this study was to
      compare balance abilities of professional dancers with nondancers on selected
      balance conditions. Fifteen dancers and 15 age- and gender-matched nondancers
      maintained one-legged stance under six combinations of visual and support surface
      conditions (Foam and Dome Test modified from two feet to one foot). Each
      condition was maintained for 30 seconds. A composite balance score was obtained
      for each subject by summing the number of seconds the individual maintained
      balance for each test condition. There was a significant difference in the mean
      composite balance score (across the six balance conditions) for the dance group
      compared with the control group (731 seconds and 563 seconds, respectively).
      Under sensory challenged conditions, it appeared that dancers were better able to
      maintain their postures upright against gravity. The balance strategies and
      techniques learned by professional dancers should be carefully analyzed to
      determine if they could be incorporated into treatment programs for nondancers
      who have balance instability and dancers who are injured.

PMID- 8749746
TI  - Recovery of muscle strength following arthroscopic meniscectomy.
AB  - The purpose of this study was to investigate the time course of spontaneous
      recovery (no supervised training) of muscle torques in the first 3 months
      postarthroscopic partial meniscectomy. This information will then be used to plan
      a clinical trial investigating the effects of rehabilitation following
      arthroscopic meniscectomy. Knee extensor and flexor strength was evaluated at
      four different velocities (60, 120, 180, and 240 degrees/sec) preoperatively and
      every 2 weeks from weeks 2-12 postsurgery. Eight subjects were evaluated on a
      Cybex II+ and 14 subjects were evaluated on a Cybex II isokinetic device. A
      repeated measures analysis of variance was used to determine possible side
      (involved and uninvolved), speed (60, 120, 180, and 240 degrees/sec), or time
      (preoperative, 2, 4, 6, 8, 10, and 12 weeks postoperatively) effects as well as
      possible interactions between these factors. Prior to partial meniscectomy, the
      involved quadriceps was significantly weaker than the uninvolved quadriceps only
      at 60 degrees/sec (15%). A further decrease in torque was noted at 2 (25-40%
      deficit depending on the velocity) and 4 weeks postsurgery at all speeds (17
      25%). The quadriceps recovered to preoperative values by 4-6 weeks postsurgery
      and stabilized at this level until the end of the study, at which time the
      quadriceps remained weaker than the contralateral side at 60 degrees/sec (14%)
      and 120 degrees/sec (12%). Prior to surgery, the involved hamstrings were
      comparable with the uninvolved hamstrings. Although significant differences
      between sides were found at week 2 postsurgery at 60 (23%) and 120 degrees/sec
      (17%), the hamstrings were fully recovered by 4 weeks postoperatively. In
      conclusion, although the quadriceps may recover to preoperative levels by 4-6
      weeks following partial meniscectomy, further recovery does not appear to be
      possible without training as the quadriceps remains weaker than the contralateral
      side up to 12 weeks postsurgery.

PMID- 8749747
TI  - The effect of nontraumatic immobilization on ankle dorsiflexion stiffness in
      rats.
AB  - Experimental evidence supports the general conclusion that 6 or more weeks of
      immobilization will cause joint contractures due to changes in the capsules of
      animals whose limbs have been traumatized. There is controversy whether
      contractures will form in 6 weeks in limbs which are free of trauma. The purpose
      of this study was to determine if range of motion would be lost in ankle joints
      of rats following nontraumatic immobilization of the hindlimb for 2 or 6 weeks.
      The right hindlimb of each animal was immobilized in a plaster cast for 2 or 6
      weeks with the left hindlimb serving as a matched control (N = 8). Nonimmobilized
      rats served as additional controls (N = 4). Following 2 or 6 weeks of
      immobilization, each rat was sacrificed and the lower leg removed at the knee. An
      electrogoniometer measured the change in dorsiflexion as torque was applied in
      increasing increments to the ankle. Load-deformation tests were performed to
      determine: 1) torque to end range of dorsiflexion, 2) joint excursion with
      application of 3.57 mNm torque for 2.5 seconds, and 3) joint excursion with
      prolonged application of 3.57 mNm torque. Only the group casted for 6 weeks
      demonstrated a significant (p < 0.05) decrease in both degrees of dorsiflexion
      and joint compliance. The group casted for 6 weeks required five times more
      torque to achieve end range than the other groups and had a 70% decrease in ankle
      dorsiflexion when a fixed torque of 3.57 mNm was applied. No significant
      differences were noted among the remaining groups. These findings suggest that in
      nontraumatically immobilized joints of rats, dense connective tissue remodels in
      such a way that mobility is unaffected after 2 weeks, but becomes quite limited
      by 6 weeks.

PMID- 8749748
TI  - Intertester reliability of the cyriax evaluation in assessing patients with
      shoulder pain.
AB  - James Cyriax's approach to diagnosis and treatment of soft tissue disorders is
      frequently used by orthopaedic and sport physical therapists. The reliability of
      using Cyriax's system to determine diagnostic categories, however, has not been
      established. The purpose of this study was to examine the intertherapist
      reliability of assessments made using Cyriax's shoulder evaluation. Twenty-one
      cases of painful shoulder were evaluated independently by two experienced
      physical therapists. Therapists used a checklist to indicate their assessment of
      each case by selecting a specific shoulder lesion or by indicating that the case
      did not fit the Cyriax model. Cohen's kappa statistic was used to measure
      intertherapist agreement. Therapists classified 19 of the 21 cases into the same
      diagnostic category for a percent agreement of 90.5%. The kappa value was .875,
      indicating "almost perfect" agreement. Both therapists classified the same four
      cases of painful shoulder as not fitting the Cyriax model of soft tissue
      examination. The results of this study show that the Cyriax evaluation can be a
      highly reliable schema for assessing patients with shoulder pain.

PMID- 8749749
TI  - The lennie test for measuring scapular position in healthy young adult females: a
      reliability and validity study.
AB  - Normal scapular rest position is neither adequately described nor agreed upon by
      authorities. The purpose of this study was to devise and describe a reliable and
      valid test (the Lennie Test) to measure scapular position, including normal
      scapular rest position. Fifteen healthy females (age 19-21 years) participated in
      the study. Horizontal and vertical scapular position in the frontal plane was
      quantified by three different investigators using a scoliometer and caliper. Same
      day radiographs were used to validate scapular position surface measurements. The
      medial borders of the scapulae were found to be parallel to the thoracic midline.
      The scapulae were on average 17.19 +/- 1.85 cm apart (at the level of the root of
      the scapulae) with the dominant arm scapula being on average 0.49 +/- 0.74 cm
      lower than the nondominant scapula. This difference in height between scapulae
      was not statistically significant (p > .01). Correlation coefficients between
      skin surface and radiograph measurements of scapular position ranged from .43 to
      .82. Intertester intraclass correlation coefficients for surface measurements of
      scapular position ranged from .64 to .86. The Lennie Test was found to have
      moderate to high intertester reliability and to provide an accurate measurement
      of the anatomical location of the scapulae based on X-ray verification. Surface
      landmark measurements for scapular position were on average within 0.56 cm and
      within 1.7 degrees of the measurements made from X-rays for linear and angular
      position, respectively. We propose the use of the Lennie Test in populations,
      healthy or otherwise, where scapular position needs to be objectively measured.

PMID- 8749750
TI  - Differential diagnosis in physical therapy evaluation of thigh pain in an
      adolescent boy.
AB  - Slipped capital femoral epiphysis (SCFE) is a condition of the adolescent hip in
      which the femoral head displaces relative to the femoral neck. This disorder is
      characterized by a synovitis of the hip joint or a mechanical limitation of
      motion with pain referred to the thigh or knee. The case described in this report
      is typical of an adolescent with SCFE. A brief review of epidemiology, etiology,
      clinical presentation, and treatment is presented to facilitate the physical
      therapist's knowledge of this condition and its proper management. Delay in
      diagnosis and treatment of SCFE may result in progression of the slip and chronic
      disability from osteoarthritis. It is imperative, therefore, that a patient
      suspected of having this condition be promptly referred to an orthopaedic surgeon
      for radiographic evaluation.

PMID- 8749751
TI  - Postoperative infection following orthopaedic surgery in human immunodeficiency
      virus-infected hemophiliacs with CD4 counts < or = 200/mm3.
AB  - Human immunodeficiency virus-infected hemophiliacs are at risk for bacterial and
      opportunistic infections with worsening immunosuppression. Thus, the risk of
      postoperative infection following orthopaedic surgery is of considerable concern.
      A survey of United States hemophilia treatment centers was conducted to determine
      the incidence of postoperative infection in human immunodeficiency virus-positive
      hemophiliacs with CD4 counts of 200 mm3 or less undergoing orthopaedic surgery. A
      total of 115 centers from 37 states reported that postoperative infection
      occurred in 10 (15.1%) of 66 patients undergoing 74 orthopaedic procedures,
      between several weeks and 5 months following surgery. In five (50%), pre
      operative infection preceded postoperative joint infection. Staphylococcus was
      the most common organism isolated in a prosthetic joint infection, in 6 of 10
      (60.0%), and the knee was the most commonly affected joint, in 9 of 10 (90.0%).
      Joint arthroplasty appeared to have 10 times the risk of nonarthroplasty
      procedures for postoperative infection (9 of 34 [26.5%] and 1 of 40 [2.5%],
      respectively, P < .01). Two subjects developed chronic osteomyelitis. The rate of
      postoperative infection in human immunodeficiency virus-positive hemophiliacs
      with CD4 counts of 200/mm3 or less appears to be high, when compared with the
      general population. Early, vigorous treatment should be instituted for suspected
      infection, antibiotic prophylaxis considered for invasive procedures, and
      surgical intervention individualized based on the balance of risks and benefits.

PMID- 8749752
TI  - Oxford meniscal bearing knee versus the Marmor knee in unicompartmental
      arthroplasty for arthrosis. A Swedish multicenter survival study.
AB  - In the Swedish Knee Arthroplasty Study, all 699 Oxford meniscal bearing cemented
      unicompartmental prostheses (Biomet, Bridgend, UK) were identified and analyzed
      regarding failure pattern and compared with all Marmor prostheses (Smith & Nephew
      Richards, Orthez, France) and with a time-, age-, and sex-matched subset of
      Marmor prostheses using survival statistics expressed as cumulative revision
      rates. After 1 year there was already a higher rate, and after 6 years the rate
      of the Oxford group was more than twice that of the Marmor group. There were 50
      revisions in the Oxford group: dislocating meniscus in 16, loosening of the
      femoral component in 6, tibial component in 4, both components in 4,
      contralateral arthrosis in 10, infection in 4, and technical failure with
      instability, pain, and/or impingement of the meniscal bearing anterior in the
      femoral condyle in 6. It is still unclear if the design with the sliding menisci
      will, in the long turn, reduce wear and loosening, thereby compensating for the
      initially inferior results. It is recommended that until this question is
      clarified, the Oxford knee should be used on a limited scale for long-term
      comparative studies only.

PMID- 8749753
TI  - Perioperative bladder management after primary total hip arthroplasty.
AB  - A retrospective review of 95 consecutive primary total hip arthroplasty patients
      was performed to assess the clinical outcome of two postoperative bladder
      management protocols. The first 49 patients (group 1) were treated with a pro re
      nata straight catheterization protocol. The next 46 patients (group 2) were
      treated with an indwelling catheterization protocol. There were no differences
      between the groups with respect to sex or age. The patients in group 2 had
      significantly lower incidences of urinary retention (P < .0005) and bladder
      distention (P < .0005) than those in group 1. Preoperative systemic diseases and
      urologic symptoms did not correlate with the occurrence of postoperative urinary
      retention or bladder distention. There were no infections in group 1. In group 2,
      one patient (2%) had bacteriuria and one patient (2%) had a urinary tract
      infection (P > .1). This trend of increased contamination in the catheterization
      group may be related to a mean catheterization duration of 72 hours.

PMID- 8749754
TI  - Comparative outcomes of total joint arthroplasty.
AB  - A prospective pre- and postoperative general health/quality-of-life factor
      comparison, using the Rand SF-36 Health Status Questionnaire (TyPE Specification,
      Quality Quest [Health Outcomes Institute, Minneapolis, MN]), was carried out on a
      consecutive series of patients with diagnosed osteoarthritis undergoing total hip
      and knee arthroplasty between March 1991 and March 1994. Study groups consisted
      of 85 total hip arthroplasty patients, 93 total knee arthroplasty patients, and
      65 single-stage bilateral total knee arthroplasty patients, all treated at the
      same specialty hospital, under the care of three senior orthopaedic surgeons. The
      average patient age was 69 years. Significant improvements in quality-of-life
      measures including physical functioning, social functioning, role
      functioning/physical problem, role functioning/emotional problem, mental health,
      energy/fatigue, pain, and change in health were noted in all hip and knee
      arthroplasty patients 6 months, 1 year, and 2 years after surgery (P < .05).
      There appeared to be no significant differences in quality-of-life measures
      between hip and knee arthroplasty patients. Results therefore indicate that total
      hip and knee arthroplasty significantly improve the functional status and quality
      of life among patients suffering from osteoarthritis.

PMID- 8749755
TI  - Predicting quality-of-life outcomes following total joint arthroplasty.
      Limitations of the SF-36 Health Status Questionnaire.
AB  - A group of 114 patients undergoing total hip and knee arthroplasty were evaluated
      to assess the effect of total joint arthroplasty on quality of life, as measured
      by the SF-36 Health Status Questionnaire, and to determine the predictive
      relationship between preoperative and postoperative scores. A highly significant
      improvement was seen comparing preoperative with postoperative scores at 2 years
      for physical function, social function, physical role function, emotional role
      function, mental health, energy, and pain. Despite a significant change in health
      status (P < or = .001), no change was seen in the patient's health perception (P
      = .61). Regression analysis failed to indicate a predictive relationship between
      preoperative and postoperative scores for any scale. Total joint arthroplasty
      dramatically improves the quality of life and function of patients afflicted with
      arthritis; however, because of the poor ability of the SF-36 to predict
      postoperative improvement on an individual basis, it cannot be used alone to
      determine treatment selection.

PMID- 8749756
TI  - Tibial polyethylene failure after primary porous-coated anatomic total knee
      arthroplasty. Aids to diagnosis and revision.
AB  - Recognizing and providing effective treatment for polyethylene failure after
      total knee arthroplasty (TKA) are challenging problems. The range of presenting
      symptoms and the usefulness of diagnostic tests are examined, and the outcome of
      surgical treatment of patients with tibial polyethylene failure is reported. From
      a consecutive series of 209 Primary Porous-Coated Anatomic (Howmedica,
      Rutherford, NJ) TKAs performed between 1984 and 1987, 18 cases (9%) required
      revision surgery. No patient experienced polyethylene failure prior to 48 months,
      and the average time to revision was 81 months after index TKA. The follow-up
      period after revision surgery averaged 24 months. Symptoms began after a period
      of good function, and preceded revision by an average of 8 months. The most
      common presenting symptom was swelling (89%), followed by stiffness (72%), pain
      (67%), and clicking (38%) or instability (22%). Single leg standing
      anteroposterior radiographs were most effective, demonstrating polyethylene
      failure by a change to increasing varus and narrowing of the polyethylene space
      in 16 of 18 cases. Arthroscopic evaluation confirmed the diagnosis in two cases.
      Five cases required tibial tubercle osteotomy for exposure, and 15 required
      complete synovectomy. Exchange of the damaged heat-pressed polyethylene insert
      with a machined insert was performed in 14 cases, exchange plus tibial tray
      revision in 3 cases, and complete knee revision in 1 case. Revision surgery
      successfully restored pain-free function and improved range of motion in 16 of 18
      cases. Survivorship analysis showed an 11% failure rate at 8 years after index
      procedure. Regular follow-up evaluation for the Primary Porous-Coated Anatomic
      TKA is suggested.

PMID- 8749757
TI  - Total hip arthroplasty in patients who have chronic lymphocytic leukemia.
AB  - Twenty patients who had chronic lymphocytic leukemia underwent 25 elective
      primary total hip arthroplasties at the Mayo Clinic. No patient had a
      postoperative prosthetic infection. No patient had an intraoperative or
      postoperative hemorrhagic complication. One patient had a revision for aseptic
      loosening. After an average follow-up period of 4.6 years, there were 84% good
      and excellent results. It is concluded that patients who have early-stage chronic
      lymphocytic leukemia may not be at increased risk for major perioperative or
      postoperative complications in total hip arthroplasty. The surgeon must remain
      vigilant for postoperative complications, but satisfactory clinical results can
      be obtained in this patient population.

PMID- 8749758
TI  - Miller-Galante unicompartmental knee arthroplasty at 2- to 5-year follow-up
      evaluations.
AB  - A consecutive series of 62 Miller-Galante (Zimmer, Warsaw, IN) unicompartmental
      knee arthroplasties were evaluated. Patients had unicompartmental degenerative
      arthritis or osteonecrosis, a sagittal plane deformity of 15 degrees or less, and
      minimal patellofemoral involvement. The average age was 69, with osteoarthritis
      in 85% and osteonecrosis in 15%. Ninety-five percent were medial and 5% lateral
      compartment replacements. The Hospital for Special Surgery knee score averaged 56
      +/- 11 before surgery and 96 +/- 5 at the final follow-up evaluation, with an
      average postoperative pain score of 48 +/- 2. Three patients suffered intra
      operative or immediate postoperative tibial plateau fractures without apparent
      sequelae, one patient required a postoperative manipulation under anesthesia, and
      one patient required an arthroscopic debridement for retained cement in the
      posterior capsular space. Limb alignment was corrected to within 5 degrees of the
      neutral mechanical axis in 77%, with 19% undercorrected and 3% overcorrected.
      Seventy percent of knees showed at least a single radiolucent line. Complete
      radiolucent lines were noted about three tibial components (6%) and progressive
      partial radiolucency was noted about four additional components (8%).

PMID- 8749759
TI  - Resection arthroplasty of the hip.
AB  - Forty-four patients with 46 resection arthroplasties performed for various
      indications were followed an average of 8.0 years. Pain relief was good or
      excellent in 77% and eradication of infection was achieved in all but one.
      Completeness of cement removal at the time of resection arthroplasty did not
      affect the results or control of infection. Patients with a history of prior
      septic total hip arthroplasty had results similar to those for patients with
      other indications for resection arthroplasty. A comprehensive review of the
      literature supports these results.

PMID- 8749760
TI  - Femoral pulse as a guide to the mechanical axis in total knee arthroplasty.
AB  - The anatomic relationship of the center of the femoral head to the femoral artery
      was studied in 140 hips in 70 patients. The coronal plane distance between the
      femoral artery 2.5 cm below the inguinal ligament and the center of the femoral
      head was measured on pelvic arteriograms. The femoral artery was found an average
      of 7.7 +/- 5 mm medial (range, -3-22 mm) to the center of the femoral head. The
      femoral artery was within 15 mm of the center of the femoral head in 93% of cases
      reviewed. A 76-cm theoretical mechanical axis was used in estimating clinical
      angular changes in the axis for a given coronal plane difference. By use of this
      model, the range of variability translates into a maximum change in the
      mechanical axis of 1.66 degrees and up to only 1.2 degrees in 95% of the cases
      reviewed. A marker placed just lateral to the palpable femoral pulse
      approximately 2 to 3 cm below the inguinal ligament is suitable as a guide to
      locate the center of the femoral head when determining the mechanical axis during
      total knee arthroplasty.

PMID- 8749761
TI  - Morphology of the transepicondylar axis and its application in primary and
      revision total knee arthroplasty.
AB  - A morphologic anatomic study was done of the lower extremity to investigate
      various relationships of the transepicondylar axis (TEA). Thirteen cadaver
      specimens were dissected and mounted to a metal frame with a pin passing through
      the TEA. The center of the knee was determined as the depth of the anterior
      intercondylar groove. The ratio of the upper leg to lower leg measured from
      femoral head center and ankle center to TEA was 1.02. The mean distance of the
      TEA to the joint line was 3.08 cm medial and 2.53 cm lateral. The mean femoral
      angle comparing the TEA to mechanical axis was 0.61 degrees varus. The mean
      tibial angle comparing the TEA to the mechanical axis was 0.4 degrees varus in
      extension and 0.43 degrees in flexion, with no significant difference in the
      lower extremity angle with flexion (P < .01). The TEA is an important landmark
      that, from this study, is virtually perpendicular to the mechanical axis of the
      lower extremity and parallels the knee flexion axis. Femoral component rotation
      and joint line positioning in total knee arthroplasty can be determined using the
      TEA.

PMID- 8749762
TI  - The posteroanterior 45 degrees flexion weight-bearing radiograph of the knee.
AB  - Biomechanical studies suggest that radiographs of the osteoarthritic knee taken
      in 30 degrees to 60 degrees of flexion more accurately demonstrate the true
      degree of articular cartilage loss than radiographs taken with the knee in full
      extension. Conventional anteroposterior weight-bearing full-extension radiographs
      were compared with posteroanterior 45 degrees flexion weight-bearing radiographs
      of 35 patients with 45 symptomatic knees (90 compartments) presenting with
      suspected osteoarthritis. In 35 compartments, there was a 2-mm or greater loss of
      joint space in the 45 degrees flexion views compared with those taken in full
      extension. Also, in 11 compartments (10 knees), there was a normal joint space on
      the full extension radiographs, but marked narrowing on the flexion view. Both
      results are statistically significant. It is concluded that the posteroanterior
      45 degrees flexion weight-bearing radiograph is a useful additional tool in the
      assessment of knees with early degenerative change.

PMID- 8749763
TI  - Total hip arthroplasty using the Zweymuller stem implanted without cement. A
      prospective study of consecutive patients with minimum 3-year follow-up period.
AB  - A prospective study was undertaken over a 2-year period to evaluate the clinical
      efficacy of using the Zweymuller femoral component (Allopro, Berne, Switzerland)
      in cementless total hip arthroplasty. Forty consecutive patients (46 hips) were
      included for final evaluation. Ninety-four percent of the femurs were classified
      as Dorr class B or C before surgery. The mean follow-up period was 50 months
      (median, 48 months). Ninety-eight percent of the hips were rated good or
      excellent clinically. No stem was classified as definitely loose. No hip has
      required any reoperation. There was no incidence of femoral or acetabular
      osteolysis up to 6 years.

PMID- 8749764
TI  - Can simple radiographs be predictive of total hip dislocation?
AB  - The usefulness of angles measured on standardized radiographs to determine
      acetabular position and predict dislocation after primary total hip arthroplasty
      (THA) was reviewed retrospectively. Seventy-four patients (97 primary THAs) were
      reviewed. All patients underwent a standardized protocol of postoperative
      radiographs which included an anteroposterior view of the pelvis and a cross
      table lateral radiograph of the hip. Two angles were measured to define
      acetabular position: the abduction angle was measured on the anteroposterior
      radiograph and the version angle was measured on the cross-table lateral
      radiograph. The values for these angles were compared in a group of known
      dislocating THAs (7 hips) and a control group of stable THAs (90 hips). These
      radiographic measurements were also assessed for their reproducibility. The
      values for the abduction and version angles were not significantly different
      between the two groups. The values for abduction and version angles for a given
      hip, from one examination to another, were reproducible. Neither the abduction
      nor the version angle was a predictor of dislocation.

PMID- 8749765
TI  - Open-knee Magnuson debridement as conservative treatment for degenerative
      osteoarthritis of the knee.
AB  - The medical records of 11 patients (average age, 37 years) who underwent 12 open
      knee Magnuson debridements for degenerative arthritis at the Cleveland Clinic
      Foundation between July 1982 and December 1991 were reviewed. The postoperative
      results were evaluated subjectively, using a modification of the National Survey
      of Total Knee Replacement questionnaire. These patients were followed with
      clinical and radiologic examinations for a mean of 73 months (range, 17-130
      months). The major indications for surgery were pain (91%) and inability to
      participate in recreational activities (55%). Although many of the changes were
      not statistically significant, the patients as a group experienced clinically
      important reductions in pain and improvements in function. More importantly, all
      patients were able to participate in recreational activities after surgery. None
      of the 11 patients have subsequently required a total knee arthroplasty. The
      Magnuson open-knee debridemert, in limited situations, should be considered as a
      temporary alternative to knee arthroplasty in the young or middle-aged, active
      individual who is not ready to accept the limitations of a total knee
      arthroplasty.

PMID- 8749766
TI  - Role of inflammatory mediators and adhesion molecules in the pathogenesis of
      aseptic loosening in total hip arthroplasties.
AB  - Concentrations of prostaglandin E2, interleukin-6, and interleukin-8 were
      determined in the hip joint synovial fluid of 20 patients undergoing primary (n =
      12) and revision (n = 8) total hip arthroplasties. Levels of soluble adhesion
      molecules were also investigated in these patients. There was a significant and
      marked increase in levels of prostaglandin E2 (P < .001), interleukin-6 (P <
      .011), interleukin-8 (P < .0002), soluble intercellular adhesion molecule 1 (P <
      .07), soluble vascular adhesion molecule 1 (P < .0006), and soluble endothelial
      leukocyte adhesion molecule 1 (P < .0003) in joint fluid of patients undergoing
      revision. On the basis of these observations, it is suggested that synovial fluid
      and its inflammatory contents could play a significant role in the pathogenesis
      of aseptic loosening in total hip arthroplasties.

PMID- 8749767
TI  - Bacterial growth on antibiotic-loaded acrylic cement. A prospective in vivo
      retrieval study.
AB  - Twenty-three patients with intraoperative culture-proven periprosthetic infection
      of the hip or knee were enrolled in a prospective cement retrieval study. All
      were treated with a two-stage technique using antibiotic-loaded acrylic cement as
      an antibiotic depot. Staphylococcus epidermidis was the most commonly isolated
      organism (19 of 23 cases). Cement and tissue were examined at second-stage
      revision for the presence of viable organisms. In this series, no organisms were
      isolated from the surface of the cement, a 100% concordance with the tissue
      cultures. A subsequent failure rate of 4.4% (1 case) was seen in this series.
      Investigation suggests this may represent reinfection from a new strain of
      organism rather than failure of eradication of the original infection.

PMID- 8749768
TI  - Influence of intraoperative femoral fractures and cerclage wiring on bone
      ingrowth into canine porous-coated femoral components.
AB  - Intraoperative femoral fractures occur more frequently with cementless than with
      cemented components. In this study, the influence of controlled femoral fractures
      fixed with cerclage wires on rotational stability and bone ingrowth into porous
      coated canine femoral components was evaluated. These data were compared with
      results of previous studies on unrecognized femoral fractures (not stabilized)
      and on the intact canine femur. Micromotion analysis revealed a significant
      increase in rotational instability in fractures not stabilized with cerclage
      wires (P < .05) compared with the intact femur. Experimentally created femoral
      fractures had a significantly deleterious effect on bone ingrowth even after
      cerclage wiring. This appears to be caused by a lack of bone ingrowth deep to the
      fracture and an increase in femoral component micromotion. In clinical practice,
      femoral fractures occurring during cementless total hip arthroplasty are a
      serious problem, and use of a cemented prosthesis is recommended if rotational
      stability of the stem cannot be ensured.

PMID- 8749769
TI  - Effects of hydroxyapatite tricalcium phosphate coating and intracancellous
      placement on bone ingrowth in titanium fibermetal implants.
AB  - The purpose of this study was to compare the host-bone response to
      hydroxyapatite/tricalcium phosphate (HA/TCP)-coated and noncoated titanium
      fibermetal implants placed in a load-sharing cancellous bone environment of the
      distal femurs of rabbits. The influence of implantation site was also
      investigated by comparing these intracancellous implants with intramedullary
      implants evaluated in a previous study. Three parameters were measured:
      percentage implant perimeter surface length in contact with new bone, percentage
      internal fibermetal surface length in contact with ingrown bone, and percentage
      of available pore space filled with bone. The HA/TCP coating significantly
      accelerated and increased bone ongrowth, new bone formation on the perimeter and
      internal surface of the implants. This effect was evident as early as 2 weeks
      after implantation. In contrast, there was no difference between HA/TCP-coated
      and noncoated implants in the bone ingrowth parameter, percentage of available
      pore space filled with bone, or pull-out strength. Scanning electron microscopy
      in the backscatter mode demonstrated that new bone formed directly onto the
      HA/TCP-coated fibers and did not usually form directly on noncoated fibers.
      Analysis of fluorochrome labeling revealed that bone formation in weeks 1 through
      4 was primarily woven and thereafter lamellar. Compared with intramedullary
      placement, intracancellous placement significantly accelerated the apposition of
      bone to the perimeter and internal surface of HA/TCP-coated implants and both
      accelerated and increased bone ingrowth as a percentage of available pore volume.
      These data show that the host response to titanium fibermetal implants is
      influenced both by HA/TCP coating and by the implantation site.

PMID- 8749770
TI  - Effect of porous coating and loading conditions on total hip femoral stem
      stability.
AB  - An examination of femoral bone-prosthesis interface behavior under different load
      types is undertaken using finite-element analysis. Three-dimensional finite
      element models are made of two designs of hip prostheses after implantation in a
      femur. Femoral geometry was determined by computed tomography scans. The models
      were loaded in one-legged stance and stairclimbing configurations. The implants
      were modeled as both smooth surfaced and porous coated. The amount of contact and
      the relative motion between bone and implant were calculated. It is shown that
      torsional loads such as occur during stairclimbing contribute to larger amounts
      of implant micromotion than does stance loading. Contact at the bone-prosthesis
      interface is more dependent on load type than on implant geometry or surface
      coating type.

PMID- 8749771
TI  - Catastrophic failure of modular zirconia-ceramic femoral head components after
      total hip arthroplasty.
AB  - Catastrophic failure of two zirconia-ceramic modular femoral heads occurred,
      despite the theoretical improved toughness of zirconia-ceramic relative to
      alumina-ceramic. This experience led the authors to return to cobalt-chromium as
      the metal of choice for articulation against polyethylene in total hip
      arthroplasty.

PMID- 8749772
TI  - Fracture of an alumina ceramic head in total hip arthroplasty.
AB  - The authors have experienced a fracture in the ceramic head in a total hip
      arthroplasty in three cases. Two of these were comminuted and the other was a
      hair-line fissure. A foreign body, perhaps from the operation, existed between
      the neck of the stem and the head in two cases (one in a comminuted fracture and
      the other in the fissure fracture). The other case had no foreign body, and,
      judging from the serial radiographs, the fracture was probably caused by weight
      bearing stress. Care must be taken during operation to avoid interposing any
      foreign body in the modular ceramic head total hip arthroplasty, and the weight
      bearing stress factor must be considered as an indication for a ceramic head
      fracture in young active patients.

PMID- 8749773
TI  - Fracture of the femoral head after ceramic-on-polyethylene total hip
      arthroplasty.
AB  - Four of 184 ceramic femoral heads that the authors used in total hip arthroplasty
      fractured from 5 to 9 months after surgery. A polyethylene-lined acetabular
      component was used in all cases. The fracture rate, 2.2%, was much higher than
      previously reported for ceramic head fractures when used with a polyethylene cup.
      The fractures occurred during normal daily activities. Possible causes included
      manufacturing defects, neck length (short in all cases), bearing diameter (28 mm
      in all cases), cone-trunnion mismatch, excess hoop stresses from impaction, or
      material deterioration. All patients were treated by removal of debris, wide
      excision of capsular tissue containing tiny abrasive fragments, exchange of the
      modular polyethylene liner, and implantation of a cobalt-chrome femoral head. The
      trunnion had been somewhat damaged by relatively brief exposure to the ceramic
      particles in every case. The authors' experience suggests that ceramic femoral
      heads be used with caution.

PMID- 8749774
TI  - Ceramic head failure.
AB  - A case of abrupt failure of the ceramic head component of a total hip
      arthroplasty is reported. The prosthesis had been inserted more than 5 years
      previously and had functioned well until its abrupt failure. At revision, the
      metal femoral and acetabular components were intact and well fixed. The broken
      ceramic head was replaced with a metal component, and the polyethylene liner
      replaced with a new one.

PMID- 8749775
TI  - Spontaneous fracture of the ceramic ball in a ceramic-polyethylene total hip
      arthroplasty.
AB  - Fractures of the ceramic ball in total hip arthroplasty are an uncommon cause of
      arthroplasty failure, and reports of this complication in ceramic-on-polyethylene
      total hip arthroplasty articulations are rare. Ball fractures have been reported
      in patients who were overweight, had high levels of activity, or had been
      injured. Other postulated contributory factors have included small ball diameter,
      defects in ceramic quality or manufacture, and errors in implantation of the
      arthroplasty. A case of a ceramic ball fracture in a ceramic and polyethylene
      articulation is reported, and the literature on such fractures is reviewed.

PMID- 8749776
TI  - Detection of alloantibodies by flow cytometry: relevance to clinical
      transplantation.
AB  - Before an organ transplant is performed, donor-recipient compatibility must be
      established by a crossmatch in much the same way as it is done for blood
      transfusions. The target antigens in organ transplantation, however, are HLA
      rather than blood group molecules, and the target cells are lymphocytes instead
      of red cells. If antidonor antibodies are detected, it is important to know
      whether they are IgG or IgM, whether they recognize T and/or B cells, and whether
      the antibody reactivity is weak or strong. These test requirements are better met
      by flow cytometry than by the standard cytotoxicity technique. A growing body of
      evidence now indicates that flow cytometry can provide more sensitive and timely
      crossmatch information than cytotoxicity assays to decide whether or not a
      transplant should be done. Flow cytometry crossmatch (FCXM) is a new and evolving
      technique that has already been found to be extremely useful in the clinical
      transplantation setting, even though significant questions yet remain about the
      precision and reliability of using flow cytometry to quantify alloantibodies and
      about the limits of normal reactivity in the assay. This article reviews
      important technical details of the FCXM and its interpretation and clinical
      application in transplantation medicine.

PMID- 8749777
TI  - Laboratory practices in reporting flow cytometry phenotyping results for
      leukemia/lymphoma specimens: results of a survey.
AB  - Laboratory directors who routinely utilize flow cytometry for at least part of
      their diagnostic evaluations in leukemias or lymphomas were surveyed by mail. The
      survey consisted of 12 questions about the flow cytometry procedures used by the
      laboratory in evaluating leukemias and lymphomas and on the format and content of
      their official report. It also requested an example of a typical
      leukemia/lymphoma report and solicited write-in comments about additional
      important aspects of using flow cytometry to evaluate leukemia and lymphomas not
      covered by the questionnaire. The goal of the survey, which was sponsored by the
      Clinical Cytometry Society (CCS), was to document what directors of flow
      cytometry laboratories currently consider to be the appropriate contents of a
      clinical leukemia/lymphoma phenotyping analysis and in what manner and detail
      they report such flow cytometry results to clinicians. The survey indicated that
      a large number of markers are routinely evaluated to phenotype leukemias (mean =
      19) and lymphomas (mean = 16). Light scatter gating, using CD45/14 to monitor the
      gate selected, is currently employed by a 2:1 ratio over the next most population
      gating strategy (CD45 vs. 90 degrees LS). Peripheral blood, bone marrow, and
      lymphoid tissue constitute the majority of clinical specimens evaluated for
      leukemia and/or lymphoma. Two-color analysis, primarily for surface markers, is
      currently the standard method for flow cytometry measurements in routine
      diagnostic studies of leukemia and lymphoma. The official flow cytometry
      laboratory report is most commonly an individual-lab-generated, paper report
      form. A discussion of the potential benefits that might result from the
      development of improved computerized reporting software and from the increased
      use of antibody-defined, lineage gating is offered. A composite report format is
      presented that demonstrates the flow measurements and quality control data
      included in the best of the example clinical reports submitted as part of the
      survey and considered important by a majority of our survey respondents. The
      example report is intended to be a basis for further discussion within the flow
      cytometry community on whether minimum reporting standards for leukemia and/or
      lymphoma flow cytometry results can and should be developed.

PMID- 8749778
TI  - Aneuploidy in breast cancer: a fluorescence in situ hybridization study.
AB  - Although ploidy is associated with the development and progression of most breast
      cancers, the value of flow cytometric ploidy as a clinical prognostic factor
      remains controversial. The technique of fluorescence in situ hybridization (FISH)
      can be used not only to determine overall ploidy, but also to assess the over
      representation or under-representation of specific chromosomes in interphase
      cells. This information may be of prognostic value. We studied 84 primary breast
      cancers and 20 metastatic tumors by FISH, using chromosome-specific fluorescent
      centromeric probes. Of these, 100 cases were also studied by DNA flow cytometry.
      The FISH studies were concordant with DNA flow cytometry with regard to
      distinguishing aneuploid from diploid tumors in 78% of cases. The FISH data
      suggested that aneuploidy arises by a process of chromosome complement doubling
      with subsequent chromosome loss. In tumors that exhibited evidence of more than
      one round of chromosome complement doubling, the selective accumulation of
      multiple copies of specific chromosomes or chromosome segments was common.
      Multiple copies of chromosomes centromeres 1, 3, and 17 were accumulated
      selectively in the cells of individual tumors more frequently than chromosomes
      centromeres 7, 11, and 16. Multiple copies of chromosomes centromeres 10 and 20
      were selectively accumulated only rarely, if at all. Aneuploidy in breast cancer
      can be divided into distinct stages using fluorescence in situ hybridization
      techniques. The stages of aneuploidy provide potential landmarks in the genetic
      evolution of this disease with possible links to chromosome-specific evolutionary
      changes.

PMID- 8749779
TI  - Intratumoral heterogeneity of DNA ploidy in breast carcinomas: a flow cytometric
      assessment of sampling techniques.
AB  - Intratumoral heterogeneity of DNA ploidy has been identified in breast
      carcinomas; however, optimal sampling methods have not been determined. In this
      study of 28 invasive breast carcinomas measuring more than 1.4 cm in greatest
      dimension, two different techniques for obtaining cells for flow cytometric DNA
      ploidy analysis were compared. Two solid pieces of tissue were taken from
      opposite halves of the tumor. A third sample was obtained by scraping multiple
      cut surfaces of the tumor. Heterogeneity of DNA ploidy was detected in 43% of
      cases. Most cases demonstrating heterogeneity contained multiple aneuploid
      populations. However, in five cases classification of the tumors as either DNA
      euploid or DNA aneuploid differed among samples. A total of 39 non-diploid
      populations were detected in 23 of the cases. Thirty-three (85%) were detected by
      scraping and 35 (90%) were detected in either one or both tissue pieces.
      Intratumoral DNA heterogeneity emphasizes the need for adequate sampling. The
      scraping technique was as effective in identifying aneuploid cell populations as
      the combined results of the two pieces of tissue and better than sampling a
      single piece of tissue. Scraping also offers the advantage of tissue conservation
      which may be critical when various analytic studies are performed.

PMID- 8749780
TI  - Flow cytometry in node-positive breast cancer: cancer and leukemia group B
      protocol 8869.
AB  - This report describes a companion flow cytometry study (Cancer and Leukemia Group
      B (CALGB)--8869) using tumors derived from patients enrolled in a large
      randomized clinical trial (CALGB-8541) performed on 1,572 patients with early
      stage, node-positive breast cancer. The CALGB initiated an adjuvant breast cancer
      trial in 1985 to determine if dose intensification (dose of drug per unit time)
      of chemotherapy was related to relapse-free and overall survival. Patients were
      randomized by pretreatment clinical variables to one of three different dosage
      regimens of chemotherapy. Using a tumor enrichment procedure, 442 paraffin
      embedded blocks were analyzed by flow cytometry, and S-phase fraction (SPF) was
      analyzed by three different methods. Ploidy analysis was performed using standard
      procedures. Tissue from 90% of the patients was suitable for ploidy analysis,
      whereas only 68% could be assessed for SPF. With a median follow-up time of 80
      months, our results show that ploidy status had no clinical utility, whereas high
      SPF predicted poorer overall survival. The rectangular fit model for SPF was more
      predictive of outcome than both the area fit model and a computer fit model
      (modfit) for SPF. In univariate analysis, patients with a low SPF (< 10%) had a
      better prognosis than those patients with a high SPF (> 10%), but they responded
      equally well to the different treatment regimens. Patients with high SPF (> 10%)
      had longer relapse-free and overall survival to high dose chemotherapy compared
      to low or standard dose chemotherapy. Multivariate analysis indicated that
      treatment intensity as well as the number of positive nodes, tumor size, steroid
      receptor status, and c-erb B-2 expression were significant in predicting overall
      and disease-free survival. The multivariate analysis, however, revealed that SPF
      was significant in predicting overall but not disease-free survival, but there
      was no longer any relationship among SPF, dose intensity, and outcome.

PMID- 8749781
TI  - Origins and clinical implications of aneuploidy in early bladder cancer.
AB  - Cytogenetic and flow cytometric studies in a variety of human solid tumors have
      suggested that gross aneuploidy may arise by a process of abrupt chromosome
      complement doubling followed by gradual chromosome loss. However, this sequence
      has not been demonstrated directly in serial studies in individual patients in
      vivo. The purpose of this study was to search for evidence of chromosome
      complement doubling and subsequent chromosome loss in flow cytometric ploidy
      patterns in serial bladder washings and/or biopsies from individual patients with
      early bladder cancer. Fifty-two patients with noninvasive bladder cancer were
      followed with serial flow cytometric DNA studies for periods ranging from 5.1 to
      42.7 months (median 15.1 months). Serial changes in DNA ploidy and S phase
      fractions were recorded and correlated with histologic and/or cytologic findings,
      response to treatment and clinical outcome. The data suggest a series of genetic
      evolutionary changes in early bladder cancer that include the initial development
      of peridiploid aneuploidy and repeated rounds of DNA content doubling with
      chromosome loss in patients with progressive disease. It is likely that gross DNA
      aneuploidy, and more specifically, DNA multiploidy and DNA hypertetraploidy, all
      arise by this mechanism. The sequence of DNA diploidy, peridiploid aneuploidy,
      near-tetraploidy, hypotetraploidy and hypertetraploidy is associated with a
      progressive increase in S phase fraction, and with increasing tumor grade; late
      steps in this ploidy sequence were often present in tumors that were refractory
      to local therapeutic measures and tumors that developed deep tumor invasion
      and/or distant metastases. We conclude that DNA multiploidy and hypertetraploidy
      are markers of advanced stages of genetic evolution in human bladder cancer.

PMID- 8749782
TI  - Use of fluorescence threshold triggering and high-speed flow cytometry for rare
      event detection.
AB  - A simple rare event detection method utilizing dual-parameter flow cytometry is
      described, which allows quantitation of specific cellular events at the level of
      two cells in 10(7) total cells. Using a standard unmodified single laser flow
      cytometer sampling at a rate of 25,000 events/sec and a fluorescence
      discriminator, 10(7) total cells are processed in 7 min. The assay involves
      precise characterization of instrument flow rates to calculate total events
      processed by the cytometer rather than accumulate total events in computer
      memory. This method of detecting rare events is demonstrated by using a model
      system of breast cancer cells labeled with a metabolically activated dye and
      serially diluted into normal peripheral blood. Potential applications include
      validation of methods to detect minimum residual disease following myeloablative
      therapy, detection of any remaining tumor cells following purging methods, and
      validation of methods to detect circulating fetal cells in maternal blood.

PMID- 8749783
TI  - Fluorescence image cytometry for measurement of nuclear DNA content in surgical
      pathology.
AB  - A study was made on various methodological aspects of fluorescence image
      cytometry (FICM) for measurement of nuclear DNA content by using CCD cameras
      attached to an epifluorescence microscope. Cell nuclei of paraffin-embedded
      specimens from mouse tissues and human prostate carcinomas were isolated and
      stained with 4'-6-diamidino-2-phenylindole (DAPI). We found that fluorescence
      fading, lamp stability, and the homogeneity of the illumination can easily be
      controlled. A camera with a signal-to-noise ratio of 53 dB gave a slightly more
      precise measurement than did a 46-dB camera. The linearity of the analysis
      results was very good. The coefficient of variation of mouse kidney standard
      cells in the DNA histograms was about 5% and 7.4% in histograms of prostate
      carcinoma biopsies. Stained cell nuclei can be stored for long periods at -20
      degrees C without impairment of quality. Comparative measurements of ploidy by
      FICM and flow cytometry confirmed the accuracy of the FICM analyses. Thus, FICM
      appears to be an easy method for quantifying the DNA content of visually
      inspected cell nuclei in surgical pathology.

PMID- 8749784
TI  - Re: Impact of ploidy analysis on clinical care of patients.

PMID- 8749785
TI  - Flow cytometer performance: fluorochrome dependent sensitivity and instrument
      configuration.

PMID- 8749786
TI  - Instrument dependent fluorochrome sensitivity.

PMID- 8749787
TI  - The relationship between parent and offspring comorbid disorders.
AB  - Data concerning alcohol and drug abuse and dependence, depression, and antisocial
      behaviors, among both subjects and their parents, were obtained from a community
      sample of 1,201 young adults. Although 35% of the sample exhibited alcohol abuse
      or dependence, 14% marijuana or cocaine abuse or dependence, and 22% reported a
      parent positive for alcoholism, evidence of comorbidity with depression or
      antisocial personality was generally rare among both parents and subjects. Over
      one third of the subjects were negative both for family history and any disorder
      of their own and 20% reported a problem in both themselves and in one or both
      parents. These findings lend only partial support for Winokur's depression
      spectrum disease hypothesis, in that diagnosed children of depressed-only
      families have a 30% chance of exhibiting substance abuse or dependence alone,
      whereas diagnosed children of alcoholic-only families have only a 7% chance of
      exhibiting depression alone.

PMID- 8749788
TI  - AA and other helpseeking for alcohol problems: former drinkers in the U.S.
      general population.
AB  - Former drinkers comprise 18.5% of the adult U.S. population. However, no
      epidemiologic data has been published on the histories of seeking help for
      alcohol problems from Alcoholics Anonymous (AA) or professional or informal
      sources of help. Using a sample of 8,057 former drinkers surveyed in the 1988
      National Health Interview Survey, prevalence and characteristics associated with
      histories of such helpseeking were investigated. About 7% of the former drinkers
      had gone to AA or sought other types of help. Characteristics associated with
      such helpseeking were a diagnosis of DSM-IV alcohol dependence or abuse, a sense
      of compulsion to drink, social pressure to cut down, and highest ever alcohol
      consumption. The effects of alcohol consumption were stronger among younger
      respondents than older ones for professional or informal helpseeking.

PMID- 8749789
TI  - To use or to refuse cocaine--the deciding factors.
AB  - Two types of narratives were obtained from 35 cocaine-addicted patients:
      narratives about using cocaine and narratives about not using cocaine. The most
      prevalent factors in using cocaine were (a) having enough money, (b) wish to end
      physical/emotional pain, and (c) wish/decision to use. The factors in narratives
      about not using cocaine were (a) patient arranged conditions to be nonstimulating
      for using cocaine, (b) recognition of bad consequences, and (c) wish/decision not
      to use. It is clear in both the cocaine-using episodes and not-using episodes
      that the patient's wish/decision is important. The conditions for using cocaine
      tended to be more external, whereas those for not using tended to be more
      internal. Similar conditions were found by a questionnaire method. A major
      treatment implication of these findings is that the focus of therapy can be
      directed to planning strategies to minimize influence of the external factors and
      to rehearse strategies to prepare for situations involving cues that influence
      use of cocaine.

PMID- 8749790
TI  - Twelve-step program use among Oxford House residents: spirituality or social
      support in sobriety?
AB  - Oxford House is a self-help, self-governed, democratic communal-living
      environment for recovering alcoholics and polysubstance abusers. In this study,
      134 male residents (M age = 34 years old) were personally interviewed on their
      recovery process and, in particular, on their experience with 12-step programs
      such as Alcoholics Anonymous (AA). Most residents (76%) reported they attended
      weekly AA meetings to assist in their recovery, mainly to acquire effective
      techniques to maintain sobriety (72%). Many AA attendees (43%) claimed no sense
      of spirituality prior to joining AA, and for most of these men (71%), attendance
      at weekly meetings was not motivated by "spirituality" aspects of the program. In
      contrast, the majority of residents (53%) attending weekly AA meetings claimed
      that a sense of fellowship with similar recovering others was their reason for
      program involvement. It appears that among men living in a communal setting with
      other recovering addicts, the need for social support for sobriety from similar
      others continues beyond the confines of their residence.

PMID- 8749791
TI  - A visual inspection protocol for measuring characteristics of used syringes.
AB  - This article reports on the use of a Visual Inspection Protocol (VIP) to measure
      observable characteristics of syringes deposited at the San Francisco needle
      exchange program. Syringes received by the program were evaluated by several
      inspectors using the VIP, and interrater reliability was assessed for each item.
      In Study I, syringes bearing individual markings made by the user (n = 568) were
      more likely to be capped at the point end and plunger end, and more often were
      new in appearance when compared with unmarked syringes (n = 2,820). In Study II,
      syringes with a short street life (n = 250) were more often new in appearance and
      were less likely to contain blood than syringes with a long street life (n =
      246). Syringes having individual markings also show signs of more careful use,
      and marking syringes may represent an ad hoc HIV prevention strategy for some
      injection drug users.

PMID- 8749792
TI  - Subgroup variation in U.S. drinking patterns: results of the 1992 national
      longitudinal alcohol epidemiologic study.
AB  - Data from the 1992 National Longitudinal Alcohol Epidemiologic Study (NLAES)
      revealed that 44% of U.S. adults 18 years of age and older were current drinkers
      who had consumed at least 12 drinks in the year preceding the interview. Twenty
      two percent were former drinkers, and 34% were lifetime abstainers. These figures
      represent an 8% decrease in the prevalence of current drinking relative to 1988.
      The proportion of current drinkers decreased with age, was higher for men than
      women, increased with education and income, was lower than average among Black
      and Hispanic adults, was highest among never-married adults and lowest among
      those who were widowed, was lower in the South than in other regions, and was
      lower in rural than urban areas. The probabilities of ever having consumed five
      or more (5+) drinks or having been intoxicated in the past year revealed similar
      patterns to those already noted, but the probabilities of heavy drinking or
      intoxication on a weekly or more frequent basis showed no variation by race or
      ethnicity. Average daily consumption of more than 1 ounce of ethanol differed
      from the preceding measure of heavy drinking in its variation across population
      subgroups, declining less sharply with age and exhibiting a U-shaped pattern with
      respect to income. Examination of the prevalence of heavy drinking among current
      drinkers rather than within the total population revealed several differences,
      the most striking reversal being that the probability of heavy drinking decreased
      with education and income. Multiple logistic regression models predicting the
      various drinking outcomes indicated that most of the differentials held true
      after adjusting for intercorrelation among the sociodemographic variables.

PMID- 8749793
TI  - Family and client characteristics as predictors of outpatient treatment outcome
      for adolescent drug abusers.
AB  - Adolescent drug abuse clients (N = 176) and their mothers, in six different
      outpatient drug-free programs, were assessed at admission and at follow-up, 15
      months after initiation of treatment. Family therapy sessions were offered in all
      six programs programs in addition to individual and group counseling. The
      pretreatment assessment procedures, and thus also the variables analyzed for
      prediction of treatment outcome, emphasized family measures (including the Family
      Environment Scale, the Family Adaptability and Cohesion Scale, the Parent
      Adolescent Communication Inventory, and other information about the family and
      the parents). Multiple regression analysis determined which of three demographic
      variables and 39 other independent pretreatment predictor variables had a
      significant relationship with each of the six outcome criteria (dependent
      variables). Four of these outcome criteria were based on client information, and
      two were based on information provided by the mother. The more positively the
      family's functioning and relationships were described by the client at
      pretreatment, the more client improvement was reported by either client or mother
      at follow-up. Eleven of the 12 predictor variables that were found to be
      significantly related to any of the treatment outcome criteria were measures, at
      pretreatment, either of the client's perceptions of family functioning, or of his
      or her relationship with parents, particularly with the mother. These findings
      show the power of the family factors as indicators of prognosis. The predictor
      variable that was found to have the largest number of significant relationships,
      predicting three of the six outcome criteria, was the "family independence"
      dimension of the FES (i.e., "The extent to which family members are encouraged to
      be assertive, self-sufficient"). It appears that the FES instrument may be quite
      effective for predicting improvements in the behavior of adolescent drug-abusing
      clients.

PMID- 8749794
TI  - Evaluating students' substance abuse assessment skills.
AB  - Graduating nursing students' abilities to assess clients for substance use were
      evaluated using two standardized patient (SP) cases. In the comprehensive health
      history case (unprompted), 55% of the study participants assessed alcohol use and
      20% assessed drug use. When prompted to conduct a substance use history, at least
      90% of the subjects asked about the quantity and frequency of alcohol use and 80%
      asked about drug use. However, in the prompted case, fewer than 10% of the
      subjects linked current alcohol and drug (AOD) use with risks and consequences,
      nor did they ask the SP if he had considered decreasing substance use. The mean
      score for communication skills used in the two assessment interviews were 3.65
      and 3.56 on a 1 to 6 Likert scale. These data point out the need for additional
      emphasis on instructing students to include AOD questions as part of routine
      assessments, what questions to ask in a substance use assessment, and how to act
      on the information received. The use of SPs is one way to obtain valid
      information about students' assessment competencies.

PMID- 8749795
TI  - Resolution from alcohol problems with and without treatment: reasons for change.
AB  - Volunteers at a local science center were asked their reasons for quitting or
      reducing their alcohol consumption. Of 248 respondents, 64 were classified as
      having had an alcohol problem from which they had successfully resolved for 1 or
      more years. Three quarters of all respondents resolved without treatment or self
      help groups, and over half (57.8%, 37 of 64) of these respondents' resolutions
      involved nonabstinence (i.e., moderate drinking). The reason for resolution most
      often endorsed by respondents was that they had "weighed the pros and cons of
      drinking and not drinking." The implications of these findings for intervention
      programs are discussed.

PMID- 8749796
TI  - Cigarette smoking in adult patients diagnosed with attention deficit
      hyperactivity disorder.
AB  - Previous work has shown that adolescent hyperactivity patients are significantly
      more likely to smoke than controls. To determine whether this pattern persists in
      adults, we studied a series of 71 patients (55 males, 16 females; mean age +/-
      SD: 33.9 +/- 11.4 years) diagnosed with ADHD. Of the males, 23 (42%) were current
      smokers, 7 (13%) were ex-smokers, and 25 (45%) were never smokers. Comparable
      figures for males in the general population in 1991, unselected for ADHD, were
      28.1%, 29.1%, and 42.1%, respectively. Of the females, 6 (38%) were current
      smokers, 5 (31%) were ex-smokers, and 5 (31%) had never smoked, as compared with
      23.5%, 19.0%, and 57.6%, respectively, in the general population. Quit ratio
      (percentage of ever-smokers who were ex-smokers) was 29% for ADHD patients,
      compared with 48.5% in the general population. The discrepancy was accounted for
      by the males, whose quit ratio was 23%, compared with 51.6% in the general
      population; the figure for ADHD females (45%) was similar to that in the general
      population (44.7%). Smokers recalled experiencing a significantly higher number
      of ADHD symptoms (11.5 +/- 1.7) as children than never smokers (9.9 +/- 2.3; p <
      .01) and scored significantly higher on several indices of childhood and adult
      comorbidity. Our findings suggest that ADHD patients overinclude smokers, and
      that these smokers find it extremely difficult to quit. For ADHD smokers, smoking
      may have begun as an attempt to manage deficits in attention and concentration,
      as suggested by greater childhood symptomatology in these patients.

PMID- 8749797
TI  - Use of lymphocytes for assessing ethanol-mediated alterations in the expression
      of hepatic cytochrome P4502E1.
AB  - The ethanol-inducible cytochrome P4502E1 (2E1) is involved in the bioactivation
      of numerous hepatotoxins and hepatocarcinogens. Because high levels of expression
      may enhance the degree and severity of hepatotoxicity from exposure to chemicals
      metabolized by this enzyme, a relatively noninvasive method to phenotypically
      distinguish those individuals exhibiting elevated concentrations of 2E1 may be
      useful. With this in mind, we examined whether ethanol exposure could alter 2E1
      in rabbit white blood cells and liver in a similar manner. Microsomes prepared
      from freshly isolated, rather than cultured cells, were used to immunochemically
      detect 2E1. The enzyme was found in lymphocytes and neutrophils. Lymphocytes,
      which comprise the majority of the white cell population in rabbits, were
      monitored for changes in 2E1 protein levels after ethanol exposure and compared
      with alterations of the hepatic enzyme. Results presented herein demonstrate that
      the degree of enhancement in 2E1 expression of lymphocytes and liver was
      dependent on the length and dose of alcohol exposure. Indeed, correlations were
      observed between blood alcohol concentrations and 2E1 content in lymphocytes (r =
      0.65, p < 0.01) and liver (r = 0.60, p < 0.01). The greatest increase in 2E1 (6-
      to 10-fold) occurred in both liver and lymphocytes at a dose of 15% ethanol for
      12 days of treatment. This induction was evident regardless of whether blood was
      taken from treated and compared with untreated rabbits or if white cells were
      obtained from the same animal before and after ethanol exposure. The latter
      findings demonstrate that changes in lymphocyte 2E1 were caused by ethanol
      exposure and not to variability in enzyme expression among rabbits.
      Interestingly, at the 10% dose, elevation of 2E1 was noted as early as 3 days,
      declined at 6 days, and at 12 and 24 days returned to slightly higher levels than
      those seen at the 3-day exposure period. This pattern of 2E1 elevation was
      observed in both the liver and lymphocytes. In fact, at all exposure periods and
      at the two doses of alcohol examined, a correlation (r = 0.70, p < 0.01) was
      observed between lymphocyte and liver 2E1 content. Collectively, these studies
      show that induction of 2E1 in lymphocytes and liver occurs in a parallel fashion.
      Furthermore, results suggest that blood 2E1 may be used in humans as a phenotypic
      marker for xenobiotic-promoted alterations in the expression of the liver enzyme.
      These findings should have a significant impact on in vivo monitoring of this
      P450 enzyme.

PMID- 8749798
TI  - Prenatal ethanol consumption alters the expression of cellular retinol binding
      protein and retinoic acid receptor mRNA in fetal rat embryo and brain.
AB  - The mechanism by which prenatal ethanol ingestion causes fetal alcohol syndrome
      (FAS) is unknown. We hypothesize that ethanol disrupts the normal function of
      retinoids in embryogenesis and differentiation, resulting in FAS. The present
      work was designed to determine if prenatal ethanol ingestion affects the
      expression of cellular retinol binding protein (CRBP) and nuclear retinoic acid
      receptors (RARs). Paired timed pregnant rats were fed a liquid diet, one group
      treated with 36% of carbohydrate calories replaced with ethanol. Maternal serum
      retinol concentrations during pregnancy peaked on the 6th day of pregnancy, but
      no difference was noted between the ethanol and control group. At the 12th and
      20th day of gestation, embryos or fetal brain were removed, and RNA was isolated
      for Northern hybridization. The abundance of CRBP mRNA was significantly elevated
      by ethanol consumption. In both the 12-day embryo (relative density of control:
      1.00 +/- 0.10; vs. ethanol: 1.87 +/- 0.30, p < 0.05) and 20-day fetal brain
      (relative density of control: 1.00 +/- 0.09; vs. ethanol: 1.46 +/- 0.09, p <
      0.01). In the embryo, ethanol ingestion resulted in a decrease in the level of
      RAR-beta mRNA (control: 1.00 +/- 0.05; vs. ethanol: 0.71 +/- 0.07, p < 0.01), but
      had no effect on RAR-alpha or RAR-gamma mRNA. In contrast to the embryo, the
      expression of both the 3.7- and 2.7-kb RAR-alpha transcripts was significantly
      greater in day 20 fetal brain of ethanol-treated rats (3.7-kb RAR-alpha control:
      1.00 +/- 0.11; vs. ethanol: 1.65 +/- 0.06; p < 0.001; 2.7-kb RAR-alpha control:
      1.00 +/- 0.14; vs. ethanol: 1.74 +/- 0.27, p < 0.05), whereas RAR-beta and RAR
      gamma expression were not altered. These observations suggest that altered
      vitamin A function is a potential factor in the embryopathy of prenatal ethanol
      exposure.

PMID- 8749799
TI  - Alcohol inhibits epidermal growth factor-stimulated progesterone secretion from
      human granulosa cells.
AB  - In this study, luteinized human granulosa cells (GC) obtained during in vitro
      fertilization procedures were used as a model system to evaluate the effects of
      ethanol (EtOH), a well-known reproductive toxin, on epidermal growth factor (EGF)
      and gonadotropin-stimulated steroidogenesis. Our results demonstrate that the
      basal progesterone (P4) and estradiol (E2) secretion by human GC in vitro was
      dependent on the ovarian stimulation protocol. EGF significantly enhanced P4, but
      not E2, secretion in human GC from clomiphene citrate (CC), human menopausal
      gonadotropin (hMG), and hMG/gonadotropin-releasing hormone agonist (GnRH-a)
      treated patients. The effects of EGF plus luteinizing hormone (LH) were additive
      in cells from the CC group, but less than additive in hMG and hMG/GnRH-a groups.
      EtOH at 20 mM or more inhibited EGF stimulated P4 secretion in human GC from all
      three patient groups. EtOH inhibited P4 secretion stimulated by EGF and LH
      cotreatment in the CC and hMG/GnRH-a groups, but not in human GC from the hMG
      treated patients. These results suggest that basal and EGF or LH-stimulated P4
      secretion by human GC, as well as the effects of EtOH, are profoundly influenced
      by the follicle's hormonal milieu.

PMID- 8749800
TI  - Fetal alcohol exposure alters the induction of immediate early gene mRNA in the
      rat prefrontal cortex after an alternation task.
AB  - The present study examined fetal alcohol effects (FAE) on the induction of the
      immediate early genes (IEGs) c-fos, jun B, c-jun, and zif268 mRNAs in the
      prefrontal cortex, hippocampus, and other brain regions after testing in an
      alternation task. Subjects were female offspring of Sprague-Dawley rats fed
      either a 35% ethanol-derived calorie diet, pair-fed with sucrose, or control-fed
      with laboratory chow during the last week of gestation. At 75-85 days of age,
      rats were food-deprived and trained in a t-maze for food reward. Then rats were
      tested at 5-sec, 30-sec, or 60-sec delays on each of 6 days. On the day of
      killing, a subset of rats was tested at the 60-sec delay for 12 trials and killed
      30 min after testing. The remaining animals were killed from their home cage and
      acted as controls. Expression of the four IEG mRNAs was examined in the brains of
      these animals using in situ hybridization. FAE rats showed a memory deficit at
      the 60-sec delay (p < 0.05), but not at the 0-sec or 30-sec delays. Testing in
      the alternation task induced a significant elevation of c-fos, c-jun, jun B, and
      zif268 mRNA expression in the prefrontal cortex, hippocampal subfields CA1 and
      CA3, and several cortical areas. However, FAE rats showed a significantly smaller
      elevation of both c-fos and jun B mRNA levels in the orbital, prelimbic, and
      anterior cingulate regions of the prefrontal cortex (p < 0.05). FAE animals also
      showed a lower expression of jun B mRNA in the caudate nucleus. Significant
      correlations between the mean performance at the 60-sec delay and mRNA expression
      of c-fos, jun B, and zif268 in the prefrontal cortical regions (p < 0.05) were
      observed. These findings suggest that fetal alcohol exposure produces changes in
      the adult prefrontal cortex that may contribute to the behavioral deficit in the
      alternation task.

PMID- 8749801
TI  - Effects of ethanol on glucose transporter expression in cultured hippocampal
      neurons.
AB  - Glucose transport was studied in primary hippocampal neuron cultures exposed to
      ethanol. Immunofluorescent staining with antibodies against neuron-specific
      enolase and glial fibrillary acidic protein identified approximately 95% of the
      cultured cells as neurons. Western blot analysis was conducted with polyclonal
      antisera to glucose transporter isoforms GLUT1 and GLUT3. As previously seen in
      astrocytes, GLUT1 protein was regulated by the culture medium glucose content.
      Exposure to 50 and 100 mM of ethanol for 5 hr induced dose-dependent reductions
      in GLUT1 and GLUT3 protein. In contrast, GLUT1 mRNA abundance was increased
      relative to controls under the same conditions. Glucose uptake, measured with the
      nonmetabolized analog, 2-deoxy-D-glucose, was reduced by 50 and 100 mM of ethanol
      in four experiments. These results indicate a direct effect of ethanol on
      neuronal glucose transporter expression, which may play a role in the neurotoxic
      effects of alcohol.

PMID- 8749802
TI  - Ethanol inhibits contractility of esophageal smooth muscle strips.
AB  - Acute ethanol (EtOH) in vivo decreases both the pressure of the lower esophageal
      sphincter (LES) and the amplitude of contractions of the smooth muscle of the
      lower esophageal body (LEB) in both man and cat. However, the mechanism of this
      inhibitory effect of EtOH is unclear. This inhibitory effect could be caused by a
      direct effect of EtOH on the esophagus or be secondary to known inhibitory
      effects of EtOH on the central nervous system. To this end, we evaluated the in
      vitro effect of EtOH on contractility of smooth muscle strips from both LES and
      LEB. Circular muscle strips from LES and LEB were isolated from cats. Changes in
      resting tension of LES strips and changes in stimulant-induced tension of LES or
      LEB strips were measured in the presence of up to five concentrations of EtOH
      (12.5- 100 mM). Stimulants included electric field stimulation (EFS) and
      carbachol. EtOH at 75 mM significantly decreased resting LES tension. EtOH also
      decreased maximal contractile responses to carbachol in both LES and LEB and
      increased the EC50 of carbachol for LES, but not LEB. EtOH also modulated EFS
      induced esophageal contractility; EtOH potentiated EFS-induced "on-response
      relaxation" in LES and decreased EFS-induced "off-response contractions" In LEB.
      EtOH-induced inhibition of esophageal contractility seemed to be reversible. EtOH
      did not result in muscle fatigue. Thus, EtOH can directly inhibit contractility
      of the esophagus, and does so reversibly and at pharmacologically relevant
      concentrations.

PMID- 8749803
TI  - Hormonal and chemical influences on the expression of class 2 aldehyde
      dehydrogenases in rat H4IIEC3 and human HuH7 hepatoma cells.
AB  - We studied the effect a variety of hormones and chemical stimuli on the activity
      of low Km aldehyde dehydrogenase (ALDH) in rat H4IIEC3 hepatoma cells and ALDH
      activity in human HuH7 hepatoma cells. The low Km enzyme in H4IIEC3 cells
      reflects ALDH2 activity, and the ALDH activity in HuH7 likely represents ALDH5.
      Of the steroid hormone family, thyroid hormone, progesterone, and
      dihydrotestosterone increased low Km ALDH activity approximately 50%, whereas
      dexamethasone and estradiol had little effect. Insulin decreased the activity of
      low Km ALDH. None of these hormones affected the activity of ALDH in HuH7 cells.
      Among second messengers, 8-bromo-cAMP and A23187 increased low Km ALDH activity;
      HuH7 ALDH activity again was unchanged. Exposure of the cells to 22 mM ethanol
      reduced low Km activity by approximately 20%, whereas hydrogen peroxide, tumor
      necrosis factor-alpha, and interleukin-1 beta had little effect. Ultraviolet
      light increased the HuH7 ALDH activity. Retinaldehyde or retinolc acid reduced
      the HuH7 ALDH activity, but had no effect on low Km ALDH activity. These data
      suggest that low Km ALDH2 can be regulated by hormones and may not be
      constitutive as previously thought, and that the HuH7 ALDH is regulated
      differently.

PMID- 8749804
TI  - Association between low contents of dopamine and serotonin in the nucleus
      accumbens and high alcohol preference.
AB  - The contents of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC),
      homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5
      HIAA) were determined in the nucleus accumbens (ACB), frontal cortex (FR),
      anterior striatum (AST), and hippocampus (HIP) of adult male rats from the F2
      generation of P x NP intercrosses. Rats were tested for their alcohol preference
      and were divided into two groups, depending on their alcohol intake. Rats in the
      high drinking group (n = 11) had ethanol intakes > 5g/kg/day, whereas the low
      drinking group (n = 15) had values < 1 g/kg/day. The content of DA in the ACB was
      lower (p < 0.001) in the high alcohol drinking group (46 +/- 2 pmol/mg tissue)
      than in the low intake rats (61 +/- 3 pmol/mg tissue). However, the contents of
      DOPAC and HVA in the ACB were similar for both groups. There were no differences
      between the two groups in the contents of DA in the FR or AST. The content of 5
      HT in the ACB was lower (p < 0.05) in high alcohol drinking rats (6.3 +/- 0.3
      pmol/mg tissue) than in the low intake group (7.0 +/- 0.2 pmol/mg tissue). The
      content of 5-HIAA in the ACB of the high intake rats was also lower than the
      level for the low drinking rats. There were no differences in the contents of 5
      HT or 5-HIAA in the FR, HIP, and AST between the two groups. The results confirm
      a phenotypic association between abnormal DA and 5-HT systems projecting to the
      ACB and high alcohol drinking behavior in the P line of rats.

PMID- 8749805
TI  - Mutations affecting sensitivity to ethanol in the nematode, Caenorhabditis
      elegans.
AB  - Mutations in nine genes have been identified in the nematode, Caenorhabditis
      elegans, which control sensitivity to ethanol. The interaction of these genes has
      been examined and used to determine a genetic pathway controlling sensitivity to
      ethanol. The nature of this pathway indicates that ethanol exerts its anesthetic
      actions at more than one site of action. These results also indicate that ethanol
      is similar in its effects to the volatile anesthetics, enflurane and isoflurane.

PMID- 8749806
TI  - The class I alcohol dehydrogenase gene is glucocorticoid-responsive in the rat
      hepatoma microcell hybrid cell line, 11-3.
AB  - Expression of the class I alcohol dehydrogenase (ADH) gene in the rat hepatoma
      microcell hybrid cell line, 11-3, was examined. The steady-state level of ADH
      mRNA in 11-3 was approximately 2-fold higher than that or rat liver and Fao, the
      parental cell line of 11-3. Removal of steroid hormones by activated charcoal
      from the serum in which 11-3 cells were maintained resulted in a significant
      decrease in the level of ADH transcript. Dexamethasone at a concentration of 1
      muM increased the ADH mRNA content in 11-3 in a time-dependent fashion, up to 48
      hr after its addition to cells that had first been deprived of steroid hormones.
      In addition, levels of ADH transcript in cells treated with dexamethasone
      increased in a dose-dependent manner, and the concentration of dexamethasone
      required to achieve half-maximal activation was 5 nM. By using the techniques of
      reverse transcription and polymerase chain reaction, and by taking advantage of a
      restriction polymorphism present between the rat and mouse ADH cDNA, we found
      that 11-3 contained both the rat and mouse class I ADH transcripts, although the
      rat sequence accounted for the great majority. Moreover, levels of both rat and
      mouse class I ADH transcripts increased in a similarly time-dependent manner in
      cells treated with dexamethasone. These results indicate that expression of class
      I ADH gene in 11-3 is high and is regulated by glucocorticoids, making the cell
      line an excellent model for the in vitro study of ADH expression.

PMID- 8749807
TI  - Selective effects of ethanol on the generation of cAMP by particular members of
      the adenylyl cyclase family.
AB  - A selective action of ethanol on major signal transduction proteins, such as
      adenylyl cyclase, has been considered to be important for certain actions of
      ethanol, and alcoholics have been demonstrated to differ from controls in
      measures of platelet adenylyl cyclase activity. Recent advances in identification
      and characterization of isoforms of adenylyl cyclase have demonstrated that there
      exists at least eight different forms of this enzyme. To examine whether the
      effect of ethanol on generation of cAMP is modified by the presence of particular
      isoforms of adenylyl cyclase within a cell, we transiently expressed each of six
      adenylyl cyclases in human embryonic kidney (HEK293) cells and measured cAMP
      accumulation in whole cells in the presence and absence of ethanol. The treatment
      of cells expressing the various adenylyl cyclases with ethanol alone did not
      enhance cAMP generation. In the presence of prostaglandin E1, cAMP generation by
      type I and type III adenylyl cyclases was insensitive to ethanol. cAMP
      accumulation generated by the other adenylyl cyclases was, however, increased by
      incubation of cells with ethanol in the presence of stimulatory agonists (e.g.,
      prostaglandin E1). Stimulation by ethanol of cAMP generation by type VII adenylyl
      cyclase was 2- to 3-fold greater than that seen with the other tested adenylyl
      cyclases. The noted stimulation of cAMP generation by ethanol was dose-dependent
      and required concurrent activation of adenylyl cyclase through the stimulatory G
      protein. The effects of ethanol were reversible and mimicked by butanol but not
      by chloroform.

PMID- 8749808
TI  - Influence of an n-6 polyunsaturated fatty acid-enriched diet on the development
      of tolerance during chronic ethanol administration in rats.
AB  - This study investigates the effects of n-6 polyunsaturated fatty acids (PUFAs),
      in the form of dietary Evening Primrose Oil (EPO) and safflower oil, on the
      development of tolerance to ethanol. The degree of fluorescence polarization of
      the fluoroprobes DPH, PROP-DPH, and TMA-DPH in isolated cortical synaptosomal
      membranes was measured. In addition, the development of tolerance, as shown by
      changes in synaptosomal membrane fluidity after an acute in vitro ethanol
      challenge, was also determined after 20 weeks of ethanol administration, either
      alone or together with a PUFA-enriched diet. Although the administration of EPO
      enriched diet did not significantly render the inner core of the cortical
      synaptosomal membrane tolerant to the acute ethanol challenge, concomitant
      administration of ethanol and EPO was found to increase further the rigidity and
      tolerance to the acute ethanol challenge in the inner core. Chronic
      administration of safflower oil, which lacks gamma-linolenic acid (18:3, n-6) but
      like EPO contains linoleic acid, either alone or together with chronic ethanol
      had no effect on synaptosomal membrane fluidity after an acute ethanol challenge.
      The results suggest that gamma-linolenic acid or its metabolites may have an
      important role to play in the development of tolerance to chronic ethanol.

PMID- 8749809
TI  - Dose-dependent effects of acute in vivo ethanol exposure on extracellular
      glutamate concentration in the cerebral cortex of the near-term fetal sheep.
AB  - The cerebral cortex is a target site of ethanol teratogenesis. L-Glutamate is a
      major excitatory neurotransmitter that plays an important neurotrophic role in
      brain development. It has been proposed that optimal function of the glutamate
      neuronal system is required for normal brain development; overactivation could
      lead to excitotoxic-induced neuronal injury, whereas underactivation could
      delay/restrict brain development. The objective of this study was to test the
      hypothesis that acute in vivo ethanol exposure alters basal glutamate release in
      the fetal cerebral cortex. The experimental approach involved measuring fetal
      cortical extracellular glutamate concentration using the technique of in vivo
      microdialysis. Near-term fetal sheep were chronically instrumented with a
      microdialysis probe placed in the parasagittal cortex. At 124 +/- 3 days of
      gestation, the effects of maternal intravenous infusion of 2 g or 4 g ethanol/kg
      maternal body weight or an equivalent volume of saline, given as four equally
      divided doses over 5 hr, on fetal cerebral cortical extracellular glutamate
      concentration were determined. None of the three treatment regimens produced
      fetal or maternal demise during the time course of the study. There was an
      ethanol dose-dependent increase, p = 0.005, in extracellular glutamate
      concentration in the fetal cerebral cortex. This increase was paroxysmal in
      nature and was not directly related to the fetal blood ethanol concentration. In
      view of the proposed role for glutamate in neuronal development, this apparent
      ethanol-induced increase in glutamate release may be important in the
      pathogenesis of ethanol teratogenesis involving the cerebral cortex.

PMID- 8749810
TI  - Stage-dependent effects of ethanol on cranial neural crest cell development:
      partial basis for the phenotypic variations observed in fetal alcohol syndrome.
AB  - Fetal alcohol syndrome (FAS) is characterized by growth retardation, mental
      deficiencies, and numerous craniofacial and neuronal anomalies; the type and
      severity of these defects may be related to the time and dose of maternal ethanol
      exposure. Ethanol administered during presomitic stages results in the typical
      FAS craniofacial phenotype and is accompanied by a loss of cranial neural crest
      cells (CNCCs) through ethanol-induced cell death. However, the stage-specific
      effects of ethanol on the CNCC population is unknown. We examined the effects of
      ethanol on CNCC populations by treating in ovo chick embryos with a single
      ethanol dose (0.43 mmol/egg) at various stages of CNCC development, and
      corresponding to the first 3-4 weeks of human gestation. Ethanol treatment
      induced cell death and reduced CNCC populations in patterns consistent with
      observed dysmorphologies of CNCC-derived cranial structures. The precise
      population affected was dependent on the timing of ethanol exposure. Treatment at
      gastrulation or neurulation induced cell death and losses of CNCC populations,
      particularly those in rostral positions, and resulted in more severe craniofacial
      defects. In contrast, treatment at early somitic stages (4-16 somites) induced
      cell death, primarily within caudal CNCC populations, but resulted in less severe
      craniofacial defects, suggesting an increased capacity for recovery. These
      results suggest that there are distinct developmental windows during which the
      CNCCs may be particularly susceptible to ethanol-induced cell death. We conclude
      that ethanol exposure seems to affect specific events adversely during neural
      crest development. The timing of embryonic ethanol exposure relative to CNCC
      development could account, in part, for the heterogenous craniofacial defects
      observed in FAS.

PMID- 8749811
TI  - Heart mitochondria response to alcohol is different than brain and liver.
AB  - Specific mitochondrial enzyme activities, mitochondrial DNA copy number, and mRNA
      levels were measured in heart, brain, and liver tissues of a group of alcohol-fed
      rats and compared with a control group. The results show a significant increase
      in mitochondrial enzyme activities (citrate synthase, complex IV, complex III,
      complex I, and complex V), as well as an increase in mitochondrial DNA in the
      cardiac tissue of the alcohol-fed animals. These data are indicative of an
      increase in mitochondrial number in the cardiac tissue that may occur as the
      result of an adaptive response to the alcoholic insult. However, in the liver and
      brain of the alcohol-treated rat, specific mitochondrial activities were
      decreased, in particular, complex III and ATP synthase, whereas levels of other
      mitochondrial enzymes (e.g., citrate synthase, specific mitochondrial
      transcripts, and mitochondrial DNA levels) do not seem to be affected. These data
      suggest that a tissue-specific response to alcohol exists that may have a common
      molecular mechanism in brain and liver, but is different in the heart.

PMID- 8749812
TI  - Effect of ethanol on the synthesis of insulin-like growth factor 1 (IGF-1) and
      the IGF-1 receptor in late prepubertal female rats: a correlation with serum IGF
      1.
AB  - For several years, it has been well accepted that insulin-like growth factor 1
      (IGF-1) plays a critical role in peripubertal growth. Recently, we have provided
      evidence to suggest that this peptide may also be involved in the sexual
      maturation process, via an action to stimulate hypothalamic luteinizing hormone
      releasing hormone release. Because ethanol (ETOH) delays puberty, an event that
      is associated with depressed growth rates and decreased growth hormone and
      luteinizing hormone (LH) secretion via actions at the hypothalamic level, we
      investigated whether this drug is capable of altering the expression of genes
      encoding IGF-1 in liver and brain, as well as the expression of the type 1 IGF
      receptor (IGF-1R) within the median eminence (ME). Also, we wanted to determine
      if any regional changes in the expression of these genes were associated with
      concomitant alterations in the serum levels of IGF-1 and LH. Rats were implanted
      with gastric cannulae on day 24 and began receiving specific control or ETOH
      diets on day 29. Rats were killed on day 34, determined to be in the late
      juvenile stage of development, and their tissues and blood were collected.
      Results indicate that the ETOH-fed rats showed a decrease (p < 0.01) in the
      expression of hepatic IGF-1 mRNA when compared with the controls, and this
      paralleled depressions in both serum IGF-1 (p < 0.01) and LH (p < 0.01). In
      contrast, no changes were detected in IGF-1 mRNA expression in the preoptic area
      and hypothalamus, as well as in IGF-1R mRNA expression within the ME. These
      results suggest that the well-known detrimental effects of ETOH on growth rates
      and the progression of the female pubertal process in the rat may be associated
      with the drug's ability to depress the hepatic synthesis of IGF-1 and the
      subsequent prepubertal circulating levels of the protein.

PMID- 8749813
TI  - Adult male rats exposed to an alcohol diet exhibit a blunted adrenocorticotropic
      hormone response to immune or physical stress: possible role of nitric oxide.
AB  - Intact adult male rats fed an alcohol [ethanol (EtOH)] diet for 10 days show
      blunted adrenocorticotropic hormone (ACTH) release in response to immune signals
      such as the cytokine interleukin-1 beta (IL-1 beta) and endotoxin
      [lipopolysaccharide (LPS)], as well as to physical stress (mild electroshocks).
      The mechanisms responsible for this effect remain poorly understood, but we have
      recently reported that decreased pituitary responsiveness to vasopressin (VP)
      might play a role. In naive rats, nitric oxide (NO) exerts a restraining
      influence on the response of the hypothalamic-pituitary (H-P) axis to cytokines
      and VP. The ability of long-term EtOH treatment to increase glutamate receptors,
      and thus NO formation, prompted us to test the hypothesis that abnormally high NO
      concentrations might modulate the influence of the drug. Blockade of the activity
      of NO synthase (NOS), the enzyme responsible for NO formation, with the arginine
      derivative L-N omega nitro-L-arginine-methylester (L-NAME), augmented the ACTH
      response to IL-1 beta or LPS in both control (C) and EtOH-fed (E) rats. Indeed,
      after L-NAME treatment, ACTH concentrations were statistically comparable in C
      and E animals injected with endotoxin or a large dose of IL-1 beta. VP-induced
      ACTH secretion also became comparable in both experimental groups after blockade
      of NOS activity. In contrast, the decreased response of the H-P axis of E animals
      to shocks was only slightly ameliorated, compared with that of C rats. It is
      therefore possible that changes in the NOergic tone induced by alcohol play a
      role in the decreased response of the H-P axis to cytokines, possibly in part by
      altering the stimulatory action of VP on the corticotrophs. On the other hand, in
      E rats NO seems to exert only a minimal influence on the central nervous system
      circuits activated by shocks.

PMID- 8749814
TI  - Age-dependent inhibition of long-term potentiation by ethanol in immature versus
      mature hippocampus.
AB  - The goal of this study was to assess the effects of ethanol on the induction of
      long-term potentiation (LTP) in hippocampal slices from immature versus mature
      rats. Population excitatory postsynaptic potentials (pEPSPs) were recorded from
      stratum radiatum of area CA1 of hippocampal slices using electrical stimulation
      of the Schaffer collateral/commissural fiber pathway. The slices were prepared
      from rats aged 15 to 25 or from 70 to 100 days. Long-term potentiation (LTP) of
      the pEPSP slope was induced using a single, theta-burst stimulus train in the
      presence or absence of 60 mM ethanol. Under control conditions, the stimulus
      train induced LTP in slices from both immature and mature animals. However, the
      magnitude of LTP was greater in slices from immature rats. When ethanol was
      present during the stimulus train, the magnitude of LTP in slices from mature
      animals did not differ significantly from the magnitude of LTP in control slices.
      However, ethanol virtually blocked the induction of LTP in slices from immature
      animals. These results indicate that memory-related synaptic plasticity in the
      hippocampus is attenuated by ethanol to a greater degree in immature versus
      mature animals.

PMID- 8749815
TI  - GABAergic transmission in the nucleus accumbens is involved in the termination of
      ethanol self-administration in rats.
AB  - Long-Evans rats (n = 12) were trained to lever-press on a fixed-ratio 4 schedule
      of reinforcement with ethanol (10% v/v) presented as the reinforcer. After
      implantation of bilateral stainless-steel guide cannulae aimed at the nucleus
      accumbens, site-specific microinjections of muscimol (1-30 ng) and bicuculline (1
      10 ng) were tested for effects on ethanol-reinforced responding. Baseline
      response patterns were characterized by initial high rates that terminated
      abruptly after approximately 20 min. Muscimol administration in the nucleus
      accumbens decreased the total number of ethanol-reinforced responses and obtained
      reinforcers. Bicuculline also decreased ethanol-reinforced responses and
      reinforcers at the highest dose tested. When a dose of bicuculline (1 ng) that
      was ineffective by itself was coadministered with an effective dose of muscimol
      (10 ng), the muscimol-induced decreases in responding were blocked. Analysis of
      response patterns showed that muscimol decreased ethanol self-administration by
      terminating responding, normally lasting 20 min, after approximately 10 min with
      no changes in local response rate. Bicuculline decreased total responding by
      producing parallel, but nonsignificant, changes in time course and response rate.
      These data suggest that GABAergic transmission in the nucleus accumbens is
      involved in the termination, but not the onset or maintenance of ethanol self
      administration. The specificity of this effect gives emphasis to the importance
      of measuring behavioral parameters, as well as products of behavior (such as
      intake volume) in the study of ethanol self-administration.

PMID- 8749816
TI  - ADH2 gene polymorphisms are determinants of alcohol pharmacokinetics.
AB  - The class I hepatic alcohol dehydrogenases (ADHs) are primarily responsible for
      ethanol metabolism in humans. Genetic polymorphism at the ADH2 locus results in
      the inheritance of isozymes of strikingly different catalytic properties. The
      most common ADH2 allele, ADH2*1, encodes the low K(m) isozyme subunit beta 1. The
      ADH2*3 allele encodes a high-activity isozyme subunit of alcohol dehydrogenase,
      beta 3, identified in approximately 25% of African-Americans. The Vmax of beta 3
      beta 3-ADH is 30 times greater than that of the beta 1 beta 1-ADH. Therefore, we
      hypothesized that the rate of ethanol metabolism, an important factor in the
      toxicity of ethanol, in persons with beta 3-containing ADH, either beta 3 beta 3-
      or beta 1 beta 3-ADH, would be faster than that of persons with only beta 1 beta
      1-ADH. We tested this hypothesis with ethanol administered orally to healthy,
      young African-Americans. Three hundred and twenty-six African-American men and
      women were genotyped using polymerase chain reaction amplification of their
      leukocyte DNA followed by hybridization with allele-specific probes. One hundred
      twelve volunteers, selected by genotype, received an oral dose of ethanol
      designed to produce a blood ethanol concentration of 80 mg/dl (0.080 g/dl), when
      the blood alcohol concentration-time curve was extrapolated back to time 0.
      Ethanol metabolic rates (beta 60s) were determined in the 112 subjects from the
      slope of the pseudolinear portion of the blood ethanol concentration-time curves.
      The mean beta 60 of African-Americans having beta 3-containing ADH isozymes had
      significantly faster ethanol elimination rates than those with only beta 1 beta 1
      ADH isozymes. There were no significant differences in body weight, ethanol
      intake in the week before testing, peak breath ethanol concentration, time to
      peak, or volume of distribution between the genotype groups. Within each of these
      groups, men had lower ethanol disappearance rates than women. These results
      demonstrate in vivo the kinetic differences of ADH2 isozymes that may influence
      individual risk for the effects of ethanol.

PMID- 8749817
TI  - Generation of neurons in the rat dentate gyrus and hippocampus: effects of
      prenatal and postnatal treatment with ethanol.
AB  - Neurons in the rat hippocampal formation (the dentate gyrus and the hippocampus)
      are born over a protracted period, from gestational day (G) 15 into adulthood.
      Dentate gyral neurons born prenatally are generated from the ventricular zone,
      whereas those born postnatally are derived from a secondary proliferative zone,
      the intrahilar zone. In contrast, hippocampal pyramidal neurons are generated
      only prenatally from the ventricular zone. In the neocortex, ethanol depresses
      the proliferation of cells in the ventricular zone and stimulates the
      proliferation of cells in the secondary proliferative zone. The present study
      tests the hypotheses that prenatal treatment with ethanol has a different effect
      on the generation of dentate gyral neurons than does postnatal ethanol treatment,
      and that these differences are determined by the timing of the ethanol exposure
      relative to the period and site of neuronal generation. Rats were treated with
      ethanol between G6 and G21 or between postnatal day (P) 4 and P12. They were
      given an injection of [3H]thymidine on G15, G18, G21, P6, P9, or P12. Rats were
      killed on P30-P35. The tissue was processed by standard autoradiographic methods
      and assessed using rigorous stereological procedures. The total number of neurons
      and the density of radiolabelled neurons in both the dentate gyrus and the CA1
      region of the hippocampus were determined. Prenatal ethanol treatment decreased
      the total number of neurons in the CA1 segment of the hippocampus and had little
      impact on neuronal number in the dentate gyrus. Likewise, the number of
      hippocampal and dentate gyral neurons generated daily was significantly lower in
      ethanol-treated rats than in controls. Postnatal treatment to ethanol, however,
      significantly increased the total number of dentate gyral neurons and the density
      of neurons generated postnatally. These postnatal changes depended on the blood
      ethanol concentration (BEC). At moderate BECs, the total number of neurons in the
      dentate gyrus and the number of neurons generated was increased. At high BECs,
      however, neuronal number and neuronal generation were decreased. Postnatal
      ethanol treatment had no effect on the number of (total or radiolabeled) CA1
      neurons. Thus, pre- and postnatal exposure to ethanol have opposite effects both
      on the number of neurons in the dentate gyrus and on the generation of neurons.
      These paradoxical effects likely result from three causes: the differential
      effects of ethanol on the two proliferative zones, the critical period of
      neuronal development, and the potentially opposite effects of moderate and high
      BEC.

PMID- 8749818
TI  - Contrasting self-report screens for alcohol problems: a review.
AB  - Current trends in conceptions of alcohol problems and provision of health care
      put increased emphasis on identifying individuals whose alcohol use and problems
      cover a range of severity. The purpose of this study is to begin to provide
      information on the relative utility of self-report measures designed to identify
      (screen for) individuals with alcohol problems. To achieve this goal, the
      empirical literature on contrasts of self-report screening measures was reviewed,
      and 13 relevant studies across diverse settings and subject populations were
      identified. The review showed that the CAGE, the Michigan Alcoholism Screening
      Test (MAST), and the short MAST (sMAST) have been the most widely studied self
      report instruments to screen for alcohol problems. Direct comparisons show the
      MAST to be more sensitive than the CAGE, but with elderly patients the CAGE may
      perform better than the MAST. Furthermore, available data suggest that the CAGE
      and the sMAST perform comparably. Finally, the CAGE, MAST, and sMAST all perform
      best when predicting criteria most similar to those the instruments were designed
      to reflect. The study concludes with a discussion of priorities for research on
      screening instruments.

PMID- 8749819
TI  - Influence of social desirability response set on self-report for assessing the
      outcome of treated alcoholics.
AB  - We studied the influence of the social desirability response set on self
      reporting by alcoholics on the outcome of treatment. Seventy-one treated
      alcoholics gave answers based on the social desirability scale (SDS) and 19
      alcohol-related items designed to evaluate abstinence, and were diagnostically
      interviewed. The serum gamma-glutamyl-transpeptidase (GGT) level was used as an
      external standard to evaluate the validity of self-reporting. As SDS scores
      increased, both the rate of abstinence reported by the subjects and the kappa
      coefficient between the self-report and diagnostic interview increased. However,
      the GGT level was significantly low in subjects who reported abstinence than
      those who reported drinking, regardless of SDS score. Thus, the social
      desirability response set may not be associated with a conscious response bias in
      alcohol-related self-reports, but may be associated with a good outcome of
      alcoholism.

PMID- 8749820
TI  - Evidence for reduced dopamine D2 receptor sensitivity in postwithdrawal
      alcoholics.
AB  - Dopamine D2 receptor sensitivity was assessed in the postwithdrawal period in
      alcoholics. Growth hormone (GH) responses to dopamine D2 agonist bromocriptine
      were measured in eight DSM-III-R alcohol-dependent subjects who were 2 weeks or
      more postalcohol withdrawal. Their responses were compared with eight
      nonalcoholic controls. After an overnight fast, each subject received 1.25 mg of
      bromocriptine orally, and serial samples of GH were taken over a 3-hr period.
      There was a significantly blunted delta GH response (mean +/- SE) in the
      alcoholic group, 2.3 mU/liter (+/- 1.4) relative to controls, 7.7 mU/liter (+/-
      1.2) (t = 2.96, df = 14, p = 0.01). There was a significantly blunted peak GH
      response (mean +/- SE) in the alcoholic group, 5.36 mU/liter (+/- 2.1) relative
      to controls, 9.04 mU/liter (+/- 5.0). This difference also reached statistical
      significance (t = 2.32, df = 14, p = 0.035). A repeated-measures ANOVA yielded a
      significant within-subjects effect of time [F(4,54) = 4.08, p = 0.0057], a
      significant within-subjects effect of group [F(1,14) = 5.6, p = 0.0329], and an
      almost significant group x time interaction [F(4,54) = 2.45, p = 0.056]. This
      result implies a relative dopamine D2 receptor subsensitivity in alcoholics in
      the postwithdrawal period.

PMID- 8749821
TI  - Carbohydrate-deficient transferrin in alcohol and nonalcohol abusers with liver
      disease.
AB  - Carbohydrate-deficient transferrin (CDT) has been demonstrated to be a marker of
      prolonged heavy alcohol consumption. We compared this marker with gamma
      glutamyltranspeptidase (GGT) and mean corpuscular volume (MCV) in alcohol and
      nonalcohol abusers with liver disease. Our results confirm that the sensitivity
      of CDT in alcoholics is high, although lower than that of GGT and MCV; however,
      the specificity of CDT was higher than that of the other two markers. This
      finding supports the notion that CDT is only partially influenced by the presence
      of liver damage, whereas increases of GGT and MCV are greatly affected by several
      factors, including liver damage and drugs. Moreover, we observed that the
      sensitivity and the specificity of CDT were greater than those of GGT and MCV in
      younger drinkers.

PMID- 8749822
TI  - Preadolescent conduct disorder behaviors predict relapse and progression of
      addiction for adolescent alcohol and drug abusers.
AB  - Increased awareness of the heterogeneity among alcohol and drug abusers has led
      to examination of the influence of concomitant psychopathology on the course of
      addiction and addictive relapse. Research among adult alcohol and drug abusers
      has found a detrimental influence of comorbid psychopathology on treatment
      outcome. Evidence exists for prevalent comorbidity, in particular conduct
      disorder (CD), among clinical samples of teen alcohol and drug abusers. However,
      little information is currently available on the relation and influence of
      psychopathology on outcome after treatment for adolescent alcohol and drug abuse.
      The current study examines the relation between CD, as assessed by the extent of
      preadolescent CD behaviors occurring before the initiation of drug use, and
      outcome for 131 adolescents over 2 years after inpatient treatment for alcohol
      and drug abuse. Drawing on recent conceptualizations of the process of relapse
      and progression of addictive behavior, CD is hypothesized to influence the
      process of relapse by altering coping efforts and intentions and increasing
      exposure to potential relapse situations. Results reveal that the extent of
      preadolescent CD behaviors is positively related to alcohol involvement in the 2
      years after treatment, and that much of this relation is accounted for by
      posttreatment cognitive coping, motivation for alcohol abstinence, interpersonal
      problems, and exposure to alcohol use. Contrary to expectations, preadolescent CD
      behaviors did not predict posttreatment drug use. These findings provide evidence
      for the influence of psychopathology on the process of relapse and progression of
      addiction after treatment for adolescent alcohol and drug abuse, and suggest that
      teens with early life CD behaviors may be at greater risk for continued alcohol
      abuse.

PMID- 8749823
TI  - Lack of plasma complement activation in severe acute alcoholic hepatitis.
AB  - To investigate whether complement pathway activation contributes to the clinical
      and histological features of acute alcoholic hepatitis, we studied the activation
      of the classical and alternative pathways in patients with alcoholic hepatitis (n
      = 20), inactive alcoholic cirrhosis (n = 8), heavy drinkers without alcoholic
      liver disease (n = 10), patients with liver disease of nonalcoholic etiology (n =
      11), and healthy control subjects (n = 18). Complement activation was evaluated
      in the alcoholic hepatitis patients by its correlation with a number of clinical
      and laboratory features indicative of the severity of liver injury, as well as by
      comparison of the patient groups. There was no significant difference in
      circulating C3 [1.02 g/liter, confidence interval (CI) = 0.76-1.28] or C4 (0.25
      g/liter, CI = 0.17-0.33) in patients with alcoholic hepatitis when compared with
      the four control groups. Factor B levels (0.24 g/liter, CI = 0.21-0.27) were
      higher in the alcoholic hepatitis patients than the control groups (p < 0.01).
      However, activation of complement (given by the ratios C3d/C3, C4d/C4, and
      Ba/factor B) was not different in alcoholic hepatitis patients when compared with
      the control groups. Univariate analysis of a wide range of clinical and
      laboratory features in the alcoholic hepatitis subjects showed a positive
      correlation between plasma C3 and serum alkaline phosphatase (r = 0.68, p =
      0.0014), AST (r = 0.55, p = 0.015), and gamma-glutamyltranspeptidase (r = 0.47, p
      = 0.035), but no correlation with clinical or laboratory features associated with
      high morbidity or mortality. There is no relationship between clinical or
      laboratory indicators of disease severity and complement activation, and it is
      unlikely that complement activation contributes to the clinical and histological
      features of alcoholic liver disease.

PMID- 8749824
TI  - Gamma-glutamyltranspeptidase and carbohydrate deficient transferrin: alternative
      measures of excessive alcohol consumption.
AB  - Both gamma-glutamyltranspeptidase and carbohydrate-deficient transferrin have
      been extensively researched as biological markers of heavy alcohol consumption.
      The current study briefly describes each test, identifies subject variables that
      influence their relative sensitivities and specificities, and examines issues
      surrounding use of the two markers in combination. In addition, this study
      suggests five design features that should characterize projects evaluating the
      validity of biochemical markers.

PMID- 8749825
TI  - Evaluation of the Alcopatch, a transdermal dosimeter for monitoring alcohol
      consumption.
AB  - BACKGROUND: The Alcopatch is an improved transdermal dosimeter for the
      measurement of alcohol consumption, by detection of ethanol in fluid excreted
      from the skin. The device is worn as a band around the ankle and provides a
      visual signal in the event of tampering. METHODS: Fourteen volunteers wore
      duplicate Alcopatches for a period of 7 or 8 days, while keeping a written record
      of their beverage alcohol consumption. Ethanol concentration in the Alcopatch was
      measured by gas chromatography and correlated with self-reported consumption.
      RESULTS: All alcohol consumption in excess of 0.25 g/kg/day resulted in
      measurable levels of ethanol in the Alcopatch. A positive correlation was
      observed between the reported consumption of ethanol (in g/kg/day) and the
      concentration of ethanol in the Alcopatch (square root, in mg/dl) (y = 0.91x +
      0.28, r = 0.61) in 12 of 14 subjects. CONCLUSIONS: The Alcopatch detected the
      consumption of beverage alcohol with high sensitivity and specificity over a
      period of 7 to 8 days and may be useful for the study of target populations.

PMID- 8749826
TI  - Neonatal diagnosis of fetal alcohol syndrome: not necessarily a hopeless
      prognosis.
AB  - A neonatal examination for fetal alcohol syndrome (FAS) should promote the
      guidance of parents, the planning of remediation for affected children, and the
      collection of prevalence data. A blinded examination of FAS characteristics
      conducted as part of a large prospective study of disadvantaged alcohol-exposed
      infants identified eight neonates who met the published criteria for FAS. These
      children were followed through the preschool years with a blinded assessment
      protocol. Seven of these children were found to have no impairment in cognitive
      and language development, when compared with their peers, and to be of average
      size. The one child who was mentally and growth retarded at follow-up who had
      been diagnosed as FAS might not have been diagnosed FAS using clinical criteria
      (as opposed to blinded research criteria), because his mother provided in
      pregnancy reports of only low alcohol intake; she later acknowledged drinking an
      average of over 21 drinks/week during the pregnancy. The findings are positive in
      that they provide hope for children who present FAS at birth, although concern
      with adverse outcomes is certainly not dispelled. In particular, the possibility
      of later-emerging impairment in more complex tasks is not ruled out.

PMID- 8749827
TI  - Specific impairments in self-regulation in children exposed to alcohol
      prenatally.
AB  - The present study utilizes a conceptual framework derived from theories of
      cognition to explain the pattern of behavioral and learning problems observed in
      subjects with fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE). Based
      on a modern interpretation of Luria's theory of self-regulation, this study used
      a neuropsychological test battery to compare 10 subjects (mean age = 13 years)
      having FAS/FAE with 10 control subjects (mean age = 12 years and 9 months).
      Subjects with FAS/FAE were relatively high functioning and did not significantly
      differ from controls with respect to receptive vocabulary. However, those with
      FAS/FAE exhibited greater difficulty than controls on tasks that involved the
      manipulation of information and goal management in working memory (e.g.,
      Planning, Controlled Oral Word Association, etc). Both groups performed equally
      well on some tasks that demanded rule learning (Delayed Response) and response
      inhibition (Go-No-Go). The above impairments were interpreted to be reflective of
      selective rather than generalized disruptions of neural networks that subserve
      working memory.

PMID- 8749828
TI  - A fetal alcohol syndrome screening tool.
AB  - The purpose of this study was to derive a multivariate, quantitative case
      definition of the fetal alcohol syndrome (FAS) facial phenotype from a
      dysmorphologist-derived gold standard and use it to develop an effective
      screening tool for identification of children at risk for FAS. The facial and
      physical features of a racially mixed group of children (0.2-10.0 years of age),
      evaluated by a single dysmorphologist in the University of Washington FAS Clinic,
      were used to determine which feature or set of features best differentiated
      between children with and without a diagnosis of FAS. The study population was
      divided into two groups balanced on gender, age at examination, race, diagnosis,
      and date of examination. Group 1 was used to identify the most differentiating
      feature(s), and group 2 was used to validate the differentiating capability of
      the feature(s). Group 1 included 97 children (20 with FAS and 77 without FAS).
      Group 2 included 97 children (19 with FAS and 78 without FAS). Discriminant
      analysis identified smooth philtrum, thin upper lip, and short palpebral fissures
      as the cluster of features that best differentiated children with and without FAS
      based on the discriminant function [D = 1.7953086 + 0.8116083 (thin upper lip) +
      2.6411562 (smooth philtrum)-3.4073780 (% predicted right palpebral fissure
      length)]. Patients with a D-score > or = 1.5 were classified as at-risk for FAS
      (screen positive). Using this cut-off value for the D-score, children in group 1
      were classified with 100% sensitivity (20 of 20 true positives) and 90.0%
      specificity (70 of 77 true negatives). The children in group 2 were classified
      with 100% sensitivity (19 of 19 true positives) and 87.3% specificity (68 of 78
      true negatives). Across all 194 patients, sensitivity was 100% [95% confidence
      interval (97-100)] and specificity was 89% [95% confidence interval (85 to 93)].
      Seventy-one percent (n = 12) of the 17 false-positives had a true classification
      of possible fetal alcohol effects. Sensitivity and specificity were unaffected by
      race, gender, and age through 10 years. The screening tool is effective at
      differentiating children with and without FAS as diagnosed by a single
      dysmorphologist (S.K.C) at the University of Washington FAS Clinic. Assessment of
      diagnostic interrater agreement between trained dysmorphologists and testing in
      other clinic populations will be needed to assess the tool's external validity.

PMID- 8749829
TI  - Trends in alcohol-related mortality among New Mexico's American Indians,
      Hispanics, and non-Hispanic whites.
AB  - Reduction of alcohol-related mortality is a national goal for health promotion
      and disease prevention. We conducted this analysis to determine whether trends in
      New Mexico's Hispanics, non-Hispanic Whites, and American Indians were consistent
      with national trends in alcohol-related mortality, and whether differences in
      drinking patterns could account for racial and ethnic differences in rates. Age
      adjusted, race-specific, and ethnic-specific alcohol-related mortality rates and
      95% confidence intervals were calculated for 5-year periods for 1958-1991 using
      New Mexico vital statistics data. We estimated the prevalence of acute and
      chronic at-risk drinking behaviors and abstinence from data collected by the
      Behavioral Risk Factor Surveillance System (BRFSS) for the period 1986-1992. We
      found that alcohol-related mortality rates varied substantially by race,
      ethnicity, sex, age, and calendar period. American Indians had the highest rates
      for both sexes. Rates increased sharply from the period 1958-1962 until the late
      1970s and the early 1980s, and then began to decrease rapidly. However, during
      the most recent decade, the rates have followed contrasting trends in the three
      ethnic and racial groups. Although rates have continued to decline among non
      Hispanic Whites, rates for Hispanics and American Indians have not declined, and
      still remain substantially higher than rates during the 1958-1962 period.
      Differences in at-risk drinking behaviors reported to the BRFSS do not explain
      the contrast in race-specific and ethnic-specific mortality rates. Although
      progress has been made in reducing national per capita alcohol consumption and
      alcohol-related mortality, certain high-risk racial and ethnic groups may not be
      sharing in the progress.

PMID- 8749830
TI  - D-fenfluramine-induced prolactin responses in postwithdrawal alcoholics and
      controls.
AB  - Serum prolactin response to the serotonin agonist D-fenfluramine were measured in
      19 DSM-111-R male alcoholics, 2.5 or more weeks postalcohol withdrawal. Prolactin
      responses were compared with nine healthy nonalcoholic male controls. After an
      overnight fast, each subject received 30 mg of D-fenfluramine orally, and serial
      samples of serum prolactin were taken over a 4-hr period. D-fenfluramine caused a
      significantly attenuated peak delta-prolactin response in the alcoholics relative
      to the controls (p = 0.05). A repeated-measures ANOVA of delta-prolactin yielded
      a significant within-subjects effect of time (p < 0.05), a within-subjects effect
      of group that reached significance (p = 0.05), and a nonsignificant group by time
      interaction. The delta-prolactin value at time points 60 and 240 min
      postadministration of the probe was significantly attenuated in the alcoholic
      group, with p < 0.05. There was also some evidence for a diminished serotonergic
      response in those alcoholics with a negative family history. The delta-prolactin
      response did not correlate with subjects' age, duration of alcohol use, duration
      of abstinence from alcohol, severity of alcohol dependence, or age of onset.
      Results imply a relative subsensitivity of the serotonin system in postwithdrawal
      alcoholics, and this may be primarily of the 5-HT2 receptor.

PMID- 8749831
TI  - Beverage effects on patterns of alcohol consumption.
AB  - In this paper an analysis is made of beverage preferences and their effect on
      alcohol consumption patterns. For this purpose we have used the 1993 Spanish
      National Household Health Survey conducted on members of the population aged 16
      or over. Beer and spirits are consumed more frequently by young people and wine
      by older people. The most consumed daily drink is wine and beer on a weekly
      basis. Men always drank more frequently and consumed a greater number of drinks
      per occasion than women for the three types of drink analyzed. The study shows
      that beverage preference is an important factor in the characterization of
      alcohol use patterns.

PMID- 8749832
TI  - Computational modeling of a putative fetal alcohol syndrome mechanism.
AB  - Fetal alcohol syndrome (FAS) refers to a pattern of birth defects occurring in a
      subpopulation of children born to women who consume alcohol during pregnancy. The
      significant medical, social, and economic impact of FAS is increasing.
      Particularly hard-hit are African-American and native-American women and
      children. Over the past two decades, basic and clinical research produced
      voluminous data on ethanol effects on developing organisms. In 1991, Duester and
      Pullarkat proposed that competition of ethanol with retinol at the alcohol
      dehydrogenase (ADH) binding site formed the basis of the FAS mechanism. This
      competition adversely affects the developing fetus caused by deregulation of
      retinoic acid (RA) homeostasis essential for proper fetal tissue development.
      Stated concisely, the FAS hypothesis is: 1. Class I ADH catalyzes the rate
      limiting step in oxidation of retinol (ROH) to RA, and ethanol (ETOH) to acetic
      acid, thus establishing competition for ADH between ROH and ETOH. 2. RA is
      required as a signal molecule for cell differentiation critical for normal fetal
      morphogenesis. 3. ADH binds ingested ETOH, thus deregulating RA homeostasis
      leading to improper RA signal transduction. Preliminary results from molecular
      modeling studies of ROH-ADH and ETOH-ADH structures, and physiologic
      pharmacokinetic modeling confirm the hypothesis with remarkable fidelity.

PMID- 8749833
TI  - Voice of the victims.
AB  - Over the past 10 years, I have been privileged to conduct educational forums for
      audiences containing many recovering alcoholics or otherwise chemically dependent
      persons. In these forums about the addictive diseases and their treatment and
      research possibilities, significant interaction with the audience members occurs.
      During these interactions, certain anecdotal phenomena seem to predominate. The
      repetitive nature of these reports suggests the need for systematic
      investigation. As with editorial comments in major medical journals, observed
      phenomena and unanswered questions from the victims can be valuable in the
      generation of testable hypotheses. Perhaps the ideas presented herein will be
      useful in the development of future research on alcohol abuse and alcohol
      dependence.

PMID- 8749834
TI  - Abundant folate in Zimbabwean beer.

PMID- 8749835
TI  - Ethanol's action on the GABAA receptor: is there a requirement for parsimony?

PMID- 8749836
TI  - Parental divorce, self-esteem and depression: an intimate relationship as a
      protective factor in young adulthood.
AB  - This study investigated whether an intimate relationship in young adulthood
      protects young people from depression in the presence of risk factors (parental
      divorce, low self-esteem in adolescence). The data were drawn from a follow-up
      survey of adolescents from the age of 16-22 (n = 1656). The prevalence of
      depression was highest among persons from divorced families who had reported low
      self-esteem at the age of 16 and who in young adulthood lacked an intimate
      relationship. An intimate relationship was found to protect young adults with the
      risk factor of earlier low self-esteem from depression irrespective of family
      background. The pattern was similar in both sexes.

PMID- 8749837
TI  - Predictors of response to amine-specific antidepressants.
AB  - Discriminant function analysis of data from a double-blind comparative trial of
      lofepramine (a noradrenaline-specific reuptake inhibitor) and fluoxetine (a
      serotonin-specific reuptake inhibitor), involving 183 patients was used to
      identify predictors of response. Psychic anxiety significantly predicted a
      positive response to antidepressant medication, whereas psychomotor retardation,
      observed sadness, subjective lassitude and somatic complaints were significant
      predictors of nonresponse. Age, gender, endogenicity, duration of illness and
      number of previous episodes were not predictive of response. Significant
      differences were found between predictors of response to fluoxetine and
      lofepramine (P < 0.001 all groups). Predictors of response to lofepramine were
      similar to overall predictors, i.e., psychic anxiety predicted responders whilst
      observed sadness, psychomotor retardation, lassitude, inability to feel and
      somatic complaints predicted nonresponders. In contrast, baseline weight loss
      predicted response to fluoxetine, whereas anxiety, reduced insight and a tendency
      to blame others significantly predicted nonresponse. Such findings have practical
      implications for the management of depressive illness.

PMID- 8749838
TI  - Retardation of mentation in depressives: Posner's covert orientation of visual
      attention test.
AB  - A double-key version of Posner's covert orientation of visual attention test,
      which involves shifting of preparation for response from one side to another, was
      administered to 32 depressives and 32 controls to evidence retardation of
      mentation in depressives and compare it to symptom-rating scales. Results showed
      depressives' overall response times to be consistently slower than controls. The
      time of maximal response preparation occurred later in depressives than in
      controls, showing clear evidence of pure retardation of mentation (not mixed with
      motor processes). This slowing of mentation was strongly correlated with
      observable psychomotor retardation but not with depressive severity.

PMID- 8749839
TI  - Behavioural aggression in panic disorder after 8 weeks' treatment with
      alprazolam.
AB  - 23 patients with a diagnosis of panic disorder with agoraphobia were randomly
      assigned to 8 weeks' treatment with alprazolam or placebo. They filled in self
      ratings before and after treatment and competed on a competitive reaction time
      task, designed to measure behavioural aggression, after 8 weeks' treatment.
      Patients taking both alprazolam and placebo rated decreased anxiety after 8
      weeks' treatment but those on alprazolam also tended to report less hostility. On
      the behavioural task, patients on alprazolam behaved more aggressively in
      response to provocation. This is the first study to confirm clinical reports of
      benzodiazepine-induced dyscontrol on an objective laboratory measure. It is
      important that it is followed up in a larger group of patients.

PMID- 8749840
TI  - GABA-elevating effects of the antidepressant/antipanic drug phenelzine in brain:
      effects of pretreatment with tranylcypromine, (-)-deprenyl and clorgyline.
AB  - The antidepressant/antipanic drug phenelzine (PLZ) is both an inhibitor of, and a
      substrate for, monoamine oxidase (MAO). PLZ also causes an elevation of brain
      levels of the amino acid neurotransmitter gamma-aminobutyric acid (GABA); this
      action can be reversed by pretreatment with the MAO inhibitor tranylcypromine
      (TCP), suggesting that the GABA-elevating effect is largely the result of a
      metabolite of PLZ formed by MAO. In the present report, rats were pretreated with
      the nonselective MAO inhibitor TCP, the MAO-A inhibitor clorgyline and the MAO-B
      inhibitor (-)-deprenyl: at the doses used, clorgyline and (-)-deprenyl caused
      selective inhibition of MAO-A and MAO-B, respectively. Both TCP and (-)-deprenyl
      caused a greater reduction in the GABA-elevating action of PLZ than did
      clorgyline, suggesting that MAO-B is more important than MAO-A in the formation
      of the active metabolite of PLZ. The results also suggest that an effect other
      than, or in addition to, inhibition of GABA transaminase by the metabolite may be
      important in the GABA-elevating action.

PMID- 8749841
TI  - Depression spectrum disease with and without depression in first-degree
      relatives.
AB  - Family history was assessed in 211 outpatients with unipolar major depression and
      diagnoses were rendered according to Winokur et al. (Winokur et al. (1978) J.
      Nerv. Ment. Dis. 166, 764-768) family history typology. The subclassification of
      Depression Spectrum Disease with Alcoholism and Depression (DSDA + D) was applied
      to those patients reporting at least one first-degree relative suffering from
      alcoholism and another first-degree relative suffering from depression (n = 103),
      while Depression Spectrum Disease with Alcoholism (DSDA) was applied to those
      patients with at least one first-degree relative suffering from alcoholism, but
      none suffering from depression (n = 108). These two groups were compared on
      demographic, clinical and biological characteristics. They were also compared
      with 162 patients who reported the presence of depression and absence of
      alcoholism in first-degree relatives, designated as Familial Pure Depressive
      Disease (FPDD) by the Winokur et al. (1978) classification. Results revealed that
      the DSDA + D group was younger, had an earlier age at onset of depression and
      experienced more episodes of depression than did the DSDA group. No differences
      were found between the two groups on biological measures. The FPDD group was more
      similar to the DSDA + D group than the DSDA group in terms of age at onset and
      number of depressives episodes. However, the FPDD group had a longer length of
      illness than either of the DSD groups. These data suggest that the DSD group
      should be more narrowly defined (excluding those with a positive family history
      of depression) in future clinical research studies.

PMID- 8749842
TI  - Neuroticism: a vulnerability marker for depression evidence from a family study.
AB  - INTRODUCTION: We investigated the relationship between depressive illness and
      personality traits from the Eysenck Personality Inventory (EPI) using data from a
      family study. METHODS: The first-degree relatives of a series of 89 probands with
      RDC major depression (MD) were subdivided by their lifetime RDC diagnosis into:
      (1) relatives recovered from MD (n = 34); (2) never-ill relatives (n = 45). The
      neuroticism (N) and extraversion (E) scores of these two groups were compared
      using a multilevel linear model, allowing for potential confounders. The
      relationship between age of onset and recurrence of MD and N scores in group 1
      was also examined. RESULTS: (1) Raised N scores were associated with a past
      history of major depression. (2) There was no such relationship for E scores. (3)
      Current depressive symptoms were also associated with an increased N score but
      this did not explain the relationship between previous major depression and N
      scores. (4) Recurrent episodes of major depression in the recovered MD relatives
      were significantly associated with increased N scores. CONCLUSION: These data
      suggest that raised N may be a vulnerability marker for major depression.

PMID- 8749843
TI  - Analysis of six protein structures predicted by comparative modeling techniques.
AB  - The protein structures of six comparative modeling targets were predicted in a
      procedure that relied on improved energy minimization, without empirical rules,
      to position all new atoms. The structures of human nucleoside diphosphate kinase
      NM23-H2, HPr from Mycoplasma capricolum, 2Fe-2S ferredoxin from Haloarcula
      marismortui, eosinophil-derived neurotoxin (EDN), mouse cellular retinoic acid
      protein I (CRABP1), and P450eryf were predicted with root mean square deviations
      on C alpha atoms of 0.69, 0.73, 1.11, 1.48, 1.69, and 1.73 A, respectively,
      compared to the target crystal structures. These differences increased as the
      sequence similarity between the target and parent proteins decreased from about
      60 to 20% identity. More residues were predicted than form the common region
      shared by the two crystal structures. In most cases insertions or deletions
      between the target and the related protein of known structure were not correctly
      positioned. One two residue insertion in CRABP1 was predicted in the correct
      conformation, while a nine residue insertion in EDN was predicted in the correct
      spatial region, although not in the correct conformation. The positions of common
      cofactors and their binding sites were predicted correctly, even when overall
      sequence similarity was low.

PMID- 8749844
TI  - An automated method for dynamic ligand design.
AB  - An automated method for the dynamic ligand design (DLD) for a binding site of
      known structure is described. The method can be used for the creation of de novo
      ligands and for the modification of existing ligands. The binding site is
      saturated with atoms (sp3 carbon atoms in the present implementation) that form
      molecules under the influence of a potential function that joins atoms to each
      other with the correct stereochemistry. The resulting molecules are linked to
      precomputed functional group minimum energy positions in the binding site. The
      generalized potential function allows atoms to sample a continuous parameter
      space that includes the Cartesian coordinates and their occupancy and type, e.g.,
      the method allows change of an sp3 carbon into an sp2 carbon or oxygen. A
      parameter space formulated in this way can then be sampled and optimized by a
      variety of methods. In this work, molecules are generated by use of a Monte Carlo
      simulated annealing algorithm. The DLD method is illustrated by its application
      to the binding site of FK506 binding protein (FKBP), an immunophilin. De novo
      ligands are designed and modification of the immunosuppressant drug FK506 are
      suggested. The results demonstrate that the dynamic ligand design approach can
      automatically construct ligands which complement both the shape and charge
      distribution of the binding site.

PMID- 8749845
TI  - Docking of a human rhinovirus neutralizing antibody onto the viral capsid.
AB  - The structure of the complex between the Fab fragment of a human rhinovirus
      serotype 2 (HRV2) neutralizing antibody (8F5) and a cross-reactive synthetic
      peptide derived from the viral capsid protein VP2 has been recently determined by
      crystallographic methods. The conformation adopted by the peptide was very
      similar to and could be superimposed onto the corresponding region of the viral
      protein VP2 of human rhinovirus 1A (HRV1A) whose three-dimensional structure is
      known. The structure of the Fab fragment determined in the complex was docked
      onto the viral capsid using the superimposition transformation found for the
      peptide. In the resulting model the Fab protrudes almost radially to about 60 A
      from the surface of the virion without any major steric problem. The Fab fragment
      was then placed on each one of the 60 equivalent epitopes using the T = 1
      icosahedral symmetry of the virus. The closest pairs of Fab fragments are related
      by viral 2-fold axes and run almost parallel to each other without clashing.
      These axes of symmetry from the viral particle could thus be coincident with the
      dyad axes of the antibodies. Furthermore, comparison of the three-dimensional
      structure of the Fab/peptide complex with the structure of the Fab fragment alone
      indicates that the flexibility of the antibody's elbow would facilitate bivalent
      attachment to the same viral particle. In accordance with the docking results,
      experimental determination of the stoichiometry of binding yielded a ratio of 30
      IgG molecules per virion also suggesting bivalent attachment of antibody 8F5 onto
      the viral particle. The neutralization of viral infectivity, being neither
      aggregation (this paper) nor inhibition of receptor binding, might be mainly
      achieved by reducing viral spread from cell to cell and/or inhibition of
      uncoating.

PMID- 8749846
TI  - Toward understanding the structure and interactions of microtubules and motor
      proteins.
AB  - To obtain an overall three-dimensional picture of the interaction between
      microtubules and the motor proteins of the kinesin family it will be necessary to
      take account of both atomic resolution structures obtained by X-ray
      crystallography and medium resolution reconstructions obtained by electron
      cryomicroscopy. We examine the problems associated with obtaining the required
      structural information from electron micrographs of vitreous ice-embedded
      microtubules decorated with motor domains. We find that the minus-end directed
      motor, ncd, decorates microtubules with an 80 A periodicity as for kinesin. Our
      theoretical analysis and experiments with ncd illustrate the difficulty in
      determining unambiguously the surface lattice organization by diffraction
      analysis of micrographs. 3D reconstructions of decorated microtubules are
      required to accurately locate the motor domains. Helical diffraction theory is
      not usually applicable because microtubules are cylindrical structures that
      rarely have complete helical symmetry. We propose using a back-projection method
      based on the long pitch helices formed by individual protofilaments. Model
      reconstructions show that this approach is feasible.

PMID- 8749847
TI  - Crystallographic structure of metal-free concanavalin A at 2.5 A resolution.
AB  - The three-dimensional structure of demetallized concanavalin A has been
      determined at 2.5 A resolution and refined to a crystallographic R-factor of 18%.
      The lectin activity of concanavalin A requires the binding of both a transition
      metal ion, generally Mn2+, and a Ca2+ ion in two neighboring sites in close
      proximity to the carbohydrate binding site. Large structural differences between
      the native and the metal-free lectin are observed in the metal-binding region and
      consequently for the residues involved in the specific binding of saccharides.
      The demetallization invokes a series of conformational changes in the protein
      backbone, apparently initiated mainly by the loss of the calcium ion. Most of the
      Mn2+ ligands retain their position, but the Ca2+ binding site is destroyed. The
      Ala207-Asp208 peptide bond, in the beta-strand neighboring the metal-binding
      sites, undergoes a cis to trans isomerization. The cis conformation for this bond
      is a highly conserved feature among the leguminous lectins and is critically
      maintained by the Ca2+ ion in metal-bound concanavalin A. A further and major
      change adjacent to the isomerized bond is an expansion of the loop containing the
      monosaccharide ligand residues Leu99 and Tyr100. The dispersion of the ligand
      residues for the monosaccharide binding site (Asn14, Agr228, Asp208, Leu99, and
      Tyr100) in metal-free concanavalin A abolishes the lectin's ability to bind
      saccharides. Since the quaternary structure of legume lectins is essential to
      their biological role, the tetramer formation was analyzed. In the crystal (pH
      5), the metal-free concanavalin A dimers associate into a tetramer that is
      similar to the native one, but with a drastically reduced number of inter-dimer
      interactions. This explains the tetramer dissociation into dimers below pH values
      of 6.5.

PMID- 8749848
TI  - Binding geometry of alpha-helices that recognize DNA.
AB  - Many transcription factors have an alpha-helix that binds to DNA bases in a
      specific fashion. The DNA-binding geometry of these recognition helices varies
      substantially. We define a set of parameters to describe the binding geometry of
      recognition helices and analyze specific stereochemical elements that determine
      particular geometries. Because the convex surface of the helix must fit into the
      concave surface of the DNA major groove, the number of degrees of freedom of the
      recognition helix is reduced from a possible six to a single angle, which we call
      alpha. The chemically interacting DNA bases and amino acid residues must lie
      along a common line and have the same spacing along it. This pairing of base
      positions with residue positions seems to restrict the binding geometry further
      to a set of discrete values for alpha.

PMID- 8749849
TI  - Atomic and residue hydrophilicity in the context of folded protein structures.
AB  - Water-protein interactions drive protein folding, stabilize the folded structure,
      and influence molecular recognition and catalysis. We analyzed the closest
      protein contacts of 10,837 water molecules in crystallographic structures to
      define a specific hydrophilicity scale reflecting specific rather than bulk
      solvent interactions. The tendencies of different atom and residue types to be
      the nearest protein neighbors of bound water molecules correlated with other
      hydrophobicity scales, verified the relevance of crystallographically determined
      water positions, and provided a direct experimental measure of water affinity in
      the context of the folded protein. This specific hydrophilicity was highly
      correlated with hydrogen-bonding capacity, and correlated better with
      experimental than computationally derived measures of partitioning between
      aqueous and organic phases. Atoms with related chemistry clustered with respect
      to the number of bound water molecules. Neutral and negatively charged oxygen
      atoms were the most hydrophilic, followed by positively-charged then neutral
      nitrogen atoms, followed by carbon and sulfur atoms. Agreement between observed
      side-chain specific hydrophilicity values and values derived from the atomic
      hydrophilicity scale showed that hydrophilicity values can be synthesized for
      different functional groups, such as unusual side or main chains, discontinuous
      epitopes, and drug molecules. Two methods of atomic hydrophilicity analysis
      provided a measure of complementarity in the interfaces of trypsin:pancreatic
      trypsin inhibitor and HIV protease:U-75875 inhibitor complexes.

PMID- 8749850
TI  - Control of crystal forms of apoferritin by site-directed mutagenesis.
AB  - Surface charges of protein molecules are not only important to biological
      functions but also crucial to the molecular assembly responsible for
      crystallization. Appropriate alteration in the surface charge distribution of a
      protein molecule induces new molecular alignment in the proper direction in the
      crystal and, hence, controls the crystal form. Apoferritin molecules are known to
      crystallize in two- and three-dimensional forms in the presence of cadmium ions,
      which bridge neighboring protein molecules. Here we report a controlled
      transformation of the apoferritin 2-D crystal by site-directed mutagenesis. In
      mutant apoferritin, two amino acid residues binding a cadmium-ion through their
      negative charge, were replaced by one type of nonionic amino acid residues. The
      amino acid residues, Asp-84 and Gln-86 in the sequence of recombinant (i.e., wild
      type) horse L-apoferritin, were replaced by Ser. The wild-type apoferritin
      yielded a hexagonal lattice 2-D crystal in the presence of cadmium ions. In
      contrast, the mutant apoferritin yielded two types of oblique crystals
      independent of the presence of cadmium ions. Image reconstruction of electron
      micrographs of the mutant crystals made clear that the mutant apoferritin
      molecules oriented themselves with the 2-fold symmetry axis perpendicular to the
      crystal plane in both crystals, while the wild-type apoferritin molecules
      oriented themselves with the 3-fold symmetry axis perpendicular to the crystal
      plane. The changes of crystal forms and molecular orientation in the 2-D crystals
      were well explained by a change of the electrostatic interactions induced by the
      mutagenesis.

PMID- 8749851
TI  - Hinge-bending motion in citrate synthase arising from normal mode calculations.
AB  - A normal mode analysis of the closed form of dimeric citrate synthase has been
      performed. The largest-amplitude collective motion predicted by this method
      compares well with the crystallographically observed hinge-bending motion. Such a
      result supports those obtained previously in the case of hinge-bending motions of
      smaller systems, such as lysozyme or hexokinase. Taken together, all these
      results suggest that low-frequency normal modes may become useful for determining
      a first approximation of the conformational path between the closed and open
      forms of these proteins.

PMID- 8749852
TI  - Fermenter production of an artificial fab fragment, rationally designed for the
      antigen cystatin, and its optimized crystallization through constant domain
      shuffling.
AB  - The synthetic antibody model "M41" was rationally designed with a binding site
      complementary to chicken egg white cystatin as the prescribed antigen. In order
      to permit comparison between the computer model and an experimental three
      dimensional structure of the artificial protein, its X-ray crystallographic
      analysis was pursued. For this purpose, M41 was expressed as a recombinant Fab
      fragment in E. coli by medium cell density fermentation employing the tightly
      regulated tetracycline promoter. The Fab fragment was efficiently purified via a
      His-6 tail fused to its heavy chain and immobilized metal affinity
      chromatography. To raise the chances for the productive formation of crystal
      packing contacts, three versions of the Fab fragment were generated with
      differing constant domains. One of these, the variant with murine C kappa and CH1
      gamma 1 domains, was successfully crystallized by microseeding in a sitting drop.
      The orthorhombic crystals exhibited symmetry of the space group P2(1)2(1)2(1)
      with unit cell dimensions a = 104.7 A, b = 113.9 A, c = 98.8 A and diffracted X
      rays to a nominal resolution of 2.5 A.

PMID- 8749853
TI  - Knowledge-based protein secondary structure assignment.
AB  - We have developed an automatic algorithm STRIDE for protein secondary structure
      assignment from atomic coordinates based on the combined use of hydrogen bond
      energy and statistically derived backbone torsional angle information. Parameters
      of the pattern recognition procedure were optimized using designations provided
      by the crystallographers as a standard-of-truth. Comparison to the currently most
      widely used technique DSSP by Kabsch and Sander (Biopolymers 22:2577-2637, 1983)
      shows that STRIDE and DSSP assign secondary structural states in 58 and 31% of
      226 protein chains in our data sample, respectively, in greater agreement with
      the specific residue-by-residue definitions provided by the discoverers of the
      structures while in 11% of the chains, the assignments are the same. STRIDE
      delineates every 11th helix and every 32nd strand more in accord with published
      assignments.

PMID- 8749854
TI  - Protein-protein interaction at crystal contacts.
AB  - Packing contacts are crystal artifacts, yet they make use of the same forces that
      govern specific recognition in protein-protein complexes and oligomeric proteins.
      They provide examples of a nonspecific protein-protein interaction which can be
      compared to biologically relevant ones. We evaluate the number and size of
      pairwise interfaces in 152 crystal forms where the asymmetric unit contains a
      monomeric protein. In those crystal forms that have no element of 2-fold
      symmetry, we find that molecules form 8 to 10 pairwise interfaces. The total area
      of the surface buried on each molecule is large, up to 4400 A2. Pairwise
      interfaces bury 200-1200 A2, like interfaces generated at random in a computer
      simulation, and less than interfaces in protease-inhibitor or antigen-antibody
      complexes, which bury 1500 A2 or more. Thus, specific contacts occurring in such
      complexes extend over a larger surface than nonspecific ones. In crystal forms
      with 2-fold symmetry, pairwise interfaces are fewer and larger on average than in
      the absence of 2-fold symmetry. Some bury 1500-2500 A2, like interfaces in
      oligomeric proteins, and create "crystal oligomers" which may have formed in the
      solution before crystallizing.

PMID- 8749855
TI  - Crystallization and preliminary X-ray crystallographic analysis of ImmE7 protein
      of colicin E7.
AB  - The ImmE7 protein, which can bind specifically to the DNase colicin E7 and
      neutralize its bactericidal activity, has been purified and crystallized in two
      different crystal forms by vapor diffusion method. The orthorhombic crystals
      belong to space group I222 or I2(1)2(1)2(1) and have unit cell dimensions a =
      75.1 A, b = 50.5 A, and c = 45.4 A. The second form is monoclinic space group
      P2(1) with cell dimensions a = 29.3 A, b = 102.7 A, c = 53.0 A, and beta = 91.5
      degrees. The orthorhombic crystals diffract to 1.8 A resolution, and are suitable
      for high-resolution X-ray analysis.

PMID- 8749856
TI  - Crystallization of the complex of human IFN-gamma and the extracellular domain of
      the IFN-gamma receptor.
AB  - A complex of human interferon-gamma (IFN-gamma) with the soluble extracellular
      domain of the IFN-gamma receptor alpha-chain (IFN-gamma-R) has been crystallised.
      Crystals of the complex were grown using PEG 4000 as the precipitating agent in
      the presence of beta-octyl glucoside. The receptor-ligand complex crystallizes in
      a monoclinic space group and diffracts to about 3.0 A resolution. Isomorphous
      crystals have been obtained with complex containing selenomethionine and cysteine
      mutants of IFN-gamma, which may facilitate the ongoing X-ray structure
      determination.

PMID- 8749857
TI  - Crystallization and preliminary crystallographic analysis of an amylopullulanase
      from the hyperthermophilic archaeon Pyrococcus woesei.
AB  - The thermostable amylopullulanase from Pyrococcus woesei was crystallized.
      Crystals, suitable for a crystallographic analysis up to a size of 0.6 mm in
      their longest dimension, have been obtained by the vapor diffusion method in a
      solution containing polyethyleneglycol 4000 (PEG 4000), isopropanol, and Tris/Cl-
      buffer pH 7.5. Crystals grown under these conditions form hexagonal rods and
      diffract to a maximum resolution of 3 A. The crystals belong to the trigonal
      lattice type with the spacegroup P3(1)21 or P3(2)21, respectively, have the cell
      dimensions a = b = 96.8 A, c = 196.2 A, alpha = beta = 90 degrees, gamma = 120
      degrees. The crystals have a theoretical packing density of 2.7 A3/Da, assuming
      one molecule with a molecule weight of 88.8 kDa in the asymmetric unit.
      Furthermore the self-rotation analysis of the dataset revealed only
      crystallographic symmetries. The merged native data of two crystals resulted in a
      88% complete dataset.

PMID- 8749858
TI  - Preliminary X-ray crystallographic analysis of Tritrichomonas foetus inosine-5'
      monophosphate dehydrogenase.
AB  - Inosine-5'-monophosphate dehydrogenase (IMPDH) from the protozoan parasite
      Tritrichomonas foetus has been expressed in E. coli and crystallized. Crystals
      were grown to 0.1 mm in each dimension in 18 to 72 h using ammonium sulfate and
      low-molecular-weight polyethylene glycols. The crystals belong to the cubic space
      group P432 with unit cell edge = 157.25 A. The enzyme is a homotetramer with each
      monomer having a molecular weight of 55,534 Da. There is one monomer per
      asymmetric unit, based on a volume/mass ratio of 2.7 A3/Da and self-rotation
      analysis. The crystals are adequately stable to allow a complete data set to be
      collected from a single crystal. Complete native data sets have been collected to
      2.3 A resolution at 4 degrees C using synchrotron radiation. High-quality
      complete data extending to 3.0 A resolution have been collected from crystals of
      four putative derivatives, and the data appear to be isomorphous with that of the
      native crystals in each case. Efforts to solve the derivatives for use in MIR
      phasing are underway.

PMID- 8749859
TI  - Crystallization and preliminary crystallographic study of human lithostathine.
AB  - Crystals of human lithostathine, a pancreatic glycoprotein which inhibits the
      growth and nucleation of calcium carbonate crystals, were grown using PEG 4000 as
      the precipitating agent. The crystals belong to the hexagonal space group P6(1)
      (or its enantiomorph P6(5)) and diffract to 1.55 A resolution. There is one
      molecule in the asymmetric unit and the crystals have 39% solvent.

PMID- 8749860
TI  - Purification, crystallization, and preliminary X-ray analysis of Bacillus
      subtilis ferrochelatase.
AB  - Bacillus subtilis ferrochelatase (EC 4.99.1.1), the final enzyme in protoheme IX
      biosynthesis, was produced with an inducible T7 RNA polymerase expression system
      in Escherichia coli and purified from the soluble cell fraction. It was
      crystallized from polyethylene glycol solution using the microseeding technique.
      The crystals diffract to a minimum Bragg spacing of 2.1 A. The space group is
      P4(2) with unit cell dimensions a = b = 50.2 A, c = 120.1 A.

PMID- 8749861
TI  - Crystallization and X-ray analysis of a single fab binding domain from protein L
      of Peptostreptococcus magnus.
AB  - Protein L is a multidomain cell wall constituent of certain strains of
      Peptostreptococcus magnus which binds to the variable domain of immunoglobulin
      kappa-light chains. A single immunoglobulin-binding domain of M(r) = 9000 from
      this protein has been isolated and crystallized. The crystals are of space group
      P4(2)2(1)2, with cell dimensions a = b = 66.9 A, c = 68.3 A, and diffract to at
      least 2.2 A resolution. The asymmetric unit of the crystal contains two molecules
      of the protein L domain, related by a noncrystallographic 2-fold axis, as
      revealed by a self-rotation function calculated with native diffraction data.

PMID- 8749862
TI  - Mathematical modeling of arterial blood flow and correlation to atherosclerosis.
AB  - The importance of arterial flow phenomena with regard to atherosclerosis
      motivates detailed studies of local cardiovascular flow dynamics. The
      quantitative analysis of flow characteristics can contribute to the understanding
      of fluid dynamic induced and favored mechanisms in atherogenesis. Numerical
      methods are very useful in supporting experimental methods and often enable the
      determination of flow variables which are difficult to obtain in experiments. Due
      to the development of improved numerical procedures for the blood specific flow
      equations and due to the application of modern computer technology, the
      calculations can be carried out under conditions describing the physiological
      situation in a realistic manner including essential effects. Here various aspects
      of arterial flow simulation are presented and discussed. The possibilities and
      difficulties of numerical simulation of arterial flow using finite element
      approximations are illustrated with the aid of the human carotid artery
      bifurcation and a distal end-to-side anastomosis model. Further convective
      diffusive mass transport in a curved tube model is considered.

PMID- 8749863
TI  - The effect of wall roughness on velocity distribution in a model of the carotid
      sinus bifurcation--analysis of laser and ultrasound Doppler velocity data.
AB  - The purpose of this work was to find out whether a rough surface in the sinus of
      a carotid model affects the flow velocity distribution and the properties of the
      corresponding ultrasonic Doppler spectrum, in view of potential application to
      the evaluation of risk of cerebral embolism. True-to-scale elastic models of
      carotid artery were used in the experiments. Experiments were performed in three
      models with varying severity of roughness and a normal (physiological healthy)
      model. The different degrees of roughness in the three models were created by
      melting graded holes in the wax cast used to make the model. Velocity data were
      collected using 4 Mhz pulsed ultrasonic and single component laser Doppler
      velocimeters. The roughness resulted in modified velocity distribution, affecting
      to various extent ultrasonic Doppler spectral parameters, in particular the
      measure of symmetry of spectral distribution.

PMID- 8749864
TI  - Analysis of the effects of measurement errors on the evaluation of propagation
      coefficients, in rubber tubes and canine aorta in vivo.
AB  - Published measurements of canine arterial propagation coefficients show large
      disparities in pulse wave attenuation and considerable variation with frequency,
      suggesting both random and systematic error. Here we devise methods of assessing
      the likely magnitude of each measurement error source, and calculate the
      individual and cumulative effects on the propagation coefficients derived using
      three different schemes to compensate for reflections: the three-point method
      (3PT), the total occlusion method (OCC) and the general iterative method applied
      to Cox's arrangement of four transducers (GEN). Results from measurements using
      impulse excitation in a latex tube show that each method accumulates error in a
      characteristic frequency pattern. The predicted error bands for OCC are very
      small except at the fundamental, and clearly exclude a significant further error
      component. The predicted 3PT error is large at low and at high frequency, and the
      error bands are better predictors of actual error than in the OCC case.
      Transducer position error is less than any one of the three pressure measurement
      errors. The predicted GEN error increases with frequency and when averaged across
      frequency is of magnitude intermediate between those for OCC and 3PT. Results for
      the OCC and GEN methods from the canine aorta in vivo generally confirm these
      trends, but the concentration of natural pulse wave energy at low frequencies
      acts to reduce low-frequency error and increase high-frequency error.

PMID- 8749865
TI  - The dynamics of pulsatile flow in distensible model arteries.
AB  - Deposits and blockages are often found in the carotid, coronary, renal and
      femoral arteries. This paper deals with laser-Doppler velocity measurements in
      models of bifurcations of the human femoral arteries. Several models were
      prepared for the studies: a simplified 35 degrees glass model, two elastic
      silicone-rubber models with a wall thickness of 1 mm and 2 mm, and true-to-scale
      rigid and elastic models. These measurements give a clearer picture of how
      hemodynamics influences the formation of atherosclerotic plaques where there is a
      hardening of the arterial walls and a loss of elasticity. In addition to the
      effects of elasticity, the influence of the flow's pulsatility were studied. The
      measurements were done in steady and pulsatile flow. From the velocity
      measurements the shear stresses were calculated.

PMID- 8749866
TI  - Forward and backward waves in the arterial system: nonlinear separation using
      Riemann invariants.
AB  - A nonlinear method has been developed to separate arterial pressure and flow
      waves into their forward and backward running components. It takes into account
      nonlinearities arising from the area-pressure relationship as well as convective
      acceleration. The method is based on the treatment of the Riemann invariants and
      requires measurements of pressure, flow and diameter at one arterial location.
      The method has been successfully tested by means of a simulation experiment in
      which the forward and backward waves were known a priori. It was shown that the
      new method is significantly more accurate in the predictions of the forward and
      backward waves when compared to the classical linear method. The new wave
      separation method was then applied to simulated aortic waves for a) a healthy
      subject and b) a subject with decreased compliance. Comparison with the classical
      linear method showed that neglecting nonlinearities leads to an overestimation of
      the forward and backward pressure wave amplitudes of the order of 5 to 10%.

PMID- 8749867
TI  - Determination of displacement, stress- and strain-distribution in the human
      heart: a FE-model on the basis of MR imaging.
AB  - The determination of characteristic cardiac parameters, such as displacement,
      stress and strain distribution are essential for an understanding of the
      mechanics of the heart. The calculation of these parameters has been limited
      until recently by the use of idealised mathematical representations of
      biventricular geometries and by applying simple material laws. On the basis of 20
      short axis heart slices and in consideration of linear and nonlinear material
      behaviour we have developed a FE model with about 100,000 degrees of freedom.
      Marching Cubes and Phong's incremental shading technique were used to visualise
      the three dimensional geometry. In a quasistatic FE analysis continuous
      distribution of regional stress and strain corresponding to the endsystolic state
      were calculated. Substantial regional variation of the Von Mises stress and the
      total strain energy were observed at all levels of the heart model. The results
      of both the linear elastic model and the model with a nonlinear material
      description (Mooney-Rivlin) were compared. While the stress distribution and peak
      stress values were found to be comparable, the displacement vectors obtained with
      the nonlinear model were generally higher in comparison with the linear elastic
      case indicating the need to include nonlinear effects.

PMID- 8749868
TI  - Adjunctive magnesium infusion therapy in acute myocardial infarction.
AB  - Intravenous magnesium therapy in acute myocardial infarction (MI) has been shown
      to be beneficial in many studies. However, these effects are not consistent from
      one trial to another, and their clinical significance is often questionable. A
      total of 78 consecutive patients were included in a prospective placebo
      controlled, randomized study of the effects of intravenous magnesium sulfate
      infusion in acute MI. Of these, 52 (66%) received intravenous streptokinase and
      the rest belonged to a non-thrombolysed group. These patients were randomized to
      receive magnesium sulfate infusion (8 mmol over 5 min followed by 65 mmol over 24
      h) or placebo. The end points were serious arrhythmias, left ventricular ejection
      fraction (LVEF) and death during hospital stay and at the end of 28 days. LVEF
      measured by radionuclide ventriculography at discharge (9 +/- 5 days) was similar
      in two groups (41 +/- 11 vs. 39 +/- 10; magnesium vs. placebo respectively, P =
      0.40). However, the LVEF of the placebo-treated thrombolysed group was higher
      than the non-thrombolysed group (42 +/- 10 vs. 37 +/- 0, P = 0.02). Incidence of
      nonsustained ventricular tachycardia (NSVT) was higher with placebo than with
      magnesium (50% vs. 23% respectively, P < 0.02, odds ratio = 0.29; 95% confidence
      intervals (CI) 0.1-0.85). Mortality during hospital stay and at the end of 28
      days was also similar in both the groups. Thus, the administration of magnesium
      infusion as an adjunct to thrombolytic therapy remains to be of questionable
      benefit.

PMID- 8749869
TI  - Mechanisms of inotropic responses of the isolated rat hearts to vanadate.
AB  - In view of the invariable development of insulin resistance in different types of
      cardiovascular diseases, considerable attention has been focused on vanadate
      because of its ability to exert insulin-like effects in the body. Since vanadate,
      like insulin, has been shown to exert a beneficial effect in diabetic
      cardiomyopathy, this study was undertaken to examine the mechanisms of its action
      on the heart. Vanadate, at 5-10 microM concentrations, produced a positive
      inotropic effect in the isolated perfused rat heart, whereas at higher
      concentrations (20 microM), it decreased the contractile force development. The
      positive inotropic effect of 10 microM vanadate was not affected by the
      pretreatment of animals with reserpine as well as the presence of propranolol or
      phenoxybenzamine in the perfusion medium. The increase in contractile force
      development due to vanadate at low (0.3-0.6 mM) concentrations of Ca2+ was
      markedly augmented, but this agent produced a negative inotropic action at high
      concentrations of Ca2+ (2.0-3.0 mM). Preperfusion of hearts with verapamil
      enhanced the positive inotropic effect of vanadate whereas hearts preperfused
      with ouabain, low sodium or amiloride showed negative inotropic effects of
      vanadate. Vanadate was found to inhibit sarcoplasmic reticular Ca(2+)-pump and
      sarcolemmal Ca(2+)-pump as well as Na(+)-K(+)-ATPase activities but the
      sarcolemmal effects were evident at lower concentrations in comparison to that on
      the sarcoplasmic reticulum. The actions of vanadate on membrane Ca2+ transport
      and ATPase systems were specific since this agent exerted no effect on
      sarcolemmal Na(+)-Ca2+ exchange or myofibrillar ATPase activities. In isolated
      cardiomyocytes suspended in buffer containing 0.5 or 1.0 mM Ca2+, vanadate
      increased the intracellular concentration of Ca2+; this increase in intracellular
      Ca2+ was more pronounced at 0.5 mM Ca2+. These results indicate that increased
      intracellular concentration of Ca2+ due to inhibition of sarcolemmal Na(+)-K(+)
      ATPase and sarcolemmal Ca(2+)-pump may be the primary mechanism of the positive
      inotropic action of vanadate in the heart. It is suggested that vanadate may
      serve as an inotropic agent and that this mechanism may contribute towards its
      beneficial effects on cardiac dysfunction in different cardiovascular diseases.

PMID- 8749870
TI  - An unusually hard lesion in an aortocoronary saphenous vein graft refractory to
      standard balloon angioplasty.
AB  - We report a case of a hard lesion in the body of an aortocoronary saphenous vein
      graft, which developed 3 years after bypass surgery and was not amenable to
      dilation during percutaneous coronary angioplasty, despite multiple balloon
      inflations at pressures reaching 13 atm. Hard lesions in aortocoronary saphenous
      vein grafts are rare but may lead to balloon angioplasty failure necessitating
      alternative angioplasty options.

PMID- 8749871
TI  - Cortical blindness during left internal mammary angiography.
AB  - Two cases of transient cortical blindness during coronary and graft angiography
      are described. In both cases, the onset of blindness was immediately preceded by
      manipulation of a guidewire in the left subclavian artery during attempts to
      selectively engage the internal mammary artery. Vertebral angiography was
      performed in the first patient and the appearances were compatible with multiple
      emboli in the posterior circulation. This patient was anticoagulated with
      intravenous heparin. His vision recovered within 72 h, but a mild visual agnosia
      persisted and it was only after nearly 3 weeks that all neurological deficits had
      resolved. The second patient recovered fully within 15 min. We postulate that
      emboli occurring as a result of manipulation of the guidewire close to the origin
      of the left vertebral artery was the cause of the cortical blindness in both
      these patients, although vasospasm as a contributory factor cannot be excluded.
      With an increasing need for investigation of patients after coronary artery
      bypass grafting, angiographers should be aware that selective internal mammary
      graft angiography may carry a higher than normal risk of neurological
      complications. The use of a guidewire to manipulate the catheter in the
      subclavian artery may increase this risk.

PMID- 8749872
TI  - Ridogrel as an adjunct to thrombolysis in acute myocardial infarction.
AB  - An open pilot study was performed to assess the safety and preliminary efficacy
      of ridogrel, a selective thromboxane-A2 synthetase inhibitor and thromboxane
      A2/prostaglandin endoperoxide receptor blocker, as adjunct to thrombolysis, with
      alteplase and heparin. In 50 patients with acute myocardial infarction, 300 mg
      ridogrel was injected intravenously in addition to alteplase and heparin.
      Ridogrel was continued orally (300 mg) twice daily for 5 days. Patency rate at
      initial (90 min) angiography, defined as thrombolysis in myocardial infarction
      perfusion grades 2 or 3, was 86%. Rescue percutaneous transluminal coronary
      angioplasty was performed in 10 patients; immediate results were good in nine,
      while a large dissection occurred in one patient. New ischemia occurred in 10
      patients within 24 h, and after the second angiogram in seven cases. Three
      underwent coronary artery bypass grafting and seven percutaneous transluminal
      coronary angioplasty without further complication. Patency rate at second
      angiography (between 6 and 24 h) was 94%. New Q-waves appeared in 56% of the
      patients; 36% had a non-Q-wave infarction and 8% had no enzyme rise. Enzymatic
      infarct size, estimated by the cumulative quantity of alpha-hydroxybutyrate
      dehydrogenase released in 72 h, was substantially smaller than in comparable
      studies with rt-PA and heparin. One patient died due to a cerebrovascular
      hemorrhage. No other deaths occurred. Bleeding complications were seen in 18
      patients (36%), necessitating blood transfusion in three. Reinfarction did not
      occur. Eventually 49 patients were discharged in good condition. Safety with
      regard to bleeding complications of ridogrel in conjunction with alteplase is
      about the same as that of aspirin. Immediate and late patency rates were high.
      Rescue percutaneous transluminal coronary angioplasty could be performed with
      relative safety and early reocclusion could be successfully dealt with by repeat
      percutaneous transluminal coronary angioplasty. Further studies with this or
      similar compounds seem warranted.

PMID- 8749873
TI  - Effect of diltiazem on coronary flow reserve in patients with microvascular
      angina.
AB  - Microvascular angina is characterized by ischemia-like symptoms in patients with
      normal coronary arteries and reduced coronary flow reserve. Clinical observations
      suggested an improvement in clinical symptomatology and exercise tolerance after
      treatment with calcium antagonists. The effect of diltiazem on coronary flow
      reserve was evaluated in controls and in patients with microvascular angina.
      Coronary flow reserve was measured in 16 normotensive patients (7 females, 9
      males, mean age 51 +/- 10 years) with angiographically normal coronary arteries.
      Coronary blood flow was determined at rest, after dipyridamole (0.5 mg/kg) and
      following intravenous administration of diltiazem (10 mg) using coronary sinus
      thermodilution technique. Coronary flow reserve was calculated as coronary blood
      flow after dipyridamole divided by coronary blood flow at rest. Patients with
      normal coronary flow reserve (coronary flow reserve > 2.0) received either
      dipyridamole alone (group 1, controls, n = 6) or dipyridamole and diltiazem
      (group 2, n = 5), whereas patients with reduced coronary flow reserve (coronary
      flow reserve < 2.0) obtained dipyridamole and diltiazem (group 3, n = 5). Resting
      coronary flow was identical in the three groups, but after maximal vasodilation
      with dipyridamole, coronary flow increased significantly more in groups 1 and 2
      than in group 3 (P < 0.05, analysis of variance (ANOVA)). Coronary flow reserve
      was 2.5 in group 1 and 2.3 in group 2, but was significantly reduced in group 3
      (1.3; P < 0.05, ANOVA). Intravenous diltiazem failed to increase coronary blood
      flow in groups 2 and 3. Therefore, diltiazem does not improve reduced coronary
      flow reserve in patients with microvascular angina, but leaves coronary flow
      reserve unaffected. The failure to ameliorate impaired coronary flow reserve with
      diltiazem is in contrast to the reported clinical improvement after calcium
      channel blockade in these patients. Thus, other factors such as structural
      abnormalities in the microcirculation or functional abnormality in smooth muscle
      relaxation not responsive to calcium channel blockade are probably responsible
      for the occurrence of myocardial ischemia in patients with microvascular angina.

PMID- 8749874
TI  - Plasma norepinephrine, myocardial damage and left ventricular systolic function
      in Chagas' heart disease.
AB  - The functional status of the sympathetic nervous system in Chagas' heart disease
      is still the subject of intense controversy. To determine the nature of the
      abnormalities of the sympathetic nervous system, we measured the plasma
      norepinephrine concentration of chagasic patients with varying degrees of
      myocardial damage. Thirty-six patients with positive serology for Chagas' disease
      were studied. Twenty patients were in Functional Class I (New York Heart
      Association), 10 were in Functional Class II and six were in Functional Classes
      III-IV. Cardiac catheterization was performed in 24 patients. The asymptomatic
      patients had a plasma norepinephrine concentration (121 +/- 37 pg/ml, mean +/-
      S.D.) not different from normal controls (103 +/- 59 pg/ml). The symptomatic
      patients, however, had a significantly elevated plasma norepinephrine
      concentration (665 +/- 354 pg/ml, P < 0.001). The baseline heart rate of the
      asymptomatic and symptomatic patients directly correlated with the plasma
      norepinephrine concentration (r = 0.69, P < 0.0001). The symptomatic patients had
      larger ventricular volumes, higher left ventricular end-diastolic pressures and
      lower ejection fractions than the asymptomatic patients and normal controls. The
      plasma norepinephrine concentration correlated linearly with the left ventricular
      end-diastolic volume (r = 0.77, P < 0.0001), and non-linearly with the ejection
      fraction (r = -0.70, P < 0.0001) and the left ventricular end-diastolic pressure
      (r = 0.53, P < 0.007). These results indicate that, in Chagas' heart disease as
      in most other cardiac diseases, sympathetic nervous system activation is a late
      and compensatory phenomenon. In other words, sympathetic activation is very
      likely related to the progressive impairment of left ventricular function.

PMID- 8749875
TI  - Relation between shortness of breath, left ventricular end diastolic pressure and
      severity of coronary artery disease.
AB  - The relation of shortness of breath to left ventricular end diastolic pressure
      and the severity of coronary artery disease was evaluated in 146 patients with
      normal segmental and global left ventricular systolic performance. None had
      chronic lung disease, cardiomyopathy, previous myocardial infarction,
      uncontrolled hypertension or unstable angina pectoris. A strong relationship was
      found between shortness of breath and elevated left ventricular end diastolic
      pressure, and a borderline relationship with the severity of coronary disease.
      Shortness of breath as a clinical symptom indicates diastolic dysfunction in this
      selected group of patients.

PMID- 8749876
TI  - The contribution of isoproterenol to the prolonged tilt test.
AB  - In this study the tilt test, in combination with isoproterenol administration,
      was used to investigate 44 patients with unexplained syncope. The reproducibility
      of the method was studied in a group of 32 patients who underwent a second test.
      The administration of isoproterenol during the test increased the sensitivity of
      the method from 52 to 70% and the reproducibility of a positive result from 61%
      to 83%, at the expense of a small decrease in specificity (from 100% to 93%).
      Isoproterenol should thus be considered an essential part of the method, although
      the low reproducibility of specific types of haemodynamic response limits its
      value in the choice and the follow up of treatment in individual cases.

PMID- 8749877
TI  - Peripartum cardiomyopathy complicating severe aortic stenosis.
AB  - A 30-year-old woman presented with cardiac failure caused by severe aortic
      stenosis and biopsy proven myocarditis 4 weeks after an uneventful pregnancy. The
      course of the myocarditis was followed and predicted by serial endomyocardial
      biopsies. Our experience suggests that peripartum cardiomyopathy should never be
      ignored as a cause of cardiac disease in the puerperium even when there is
      another, more obvious, pathology and we report the efficacy of serial transvenous
      cardiac biopsies in timing aortic valve replacement in this patient.

PMID- 8749878
TI  - Comparative study of efficacy and safety of low-dose diltiazem or betaxolol in
      combination with digoxin to control ventricular rate in chronic atrial
      fibrillation: randomized crossover study.
AB  - BACKGROUND: The combination therapy of low-dose diltiazem or bexatolol with
      digoxin can be a useful adjunct for achieving heart rate control with minimal
      side effects. But there has not been a study including patients with impaired
      left ventricular function and evaluating whether the beneficial effects of
      medication will be maintained during a follow-up period. OBJECTIVES: The purpose
      of this study was three-fold: (1) to compare the efficacy of digoxin with low
      dose diltiazem and digoxin with low-dose betaxolol on randomized crossover study;
      (2) to evaluate whether the beneficial effects of medication will be maintained
      after 7 months; (3) to evaluate the safety of the combination therapy in patients
      with impaired left ventricular function. METHODS: We did a prospective randomized
      crossover study in 35 patients with chronic atrial fibrillation (AF) including 15
      patients with left ventricular dysfunction. After enrollment, each patient was
      evaluated for heart rate, blood pressure, rate-pressure products, maximal
      exercise tolerance at rest and during symptom-limited treadmill test before
      medication, at 4 weeks after medication of digoxin (0.125-0.5 mg daily) with
      diltiazem (90 mg twice daily), and at 4 weeks after digoxin with betaxolol (20 mg
      once daily). We performed 24-h ambulatory electrocardiogram (ECG) in 15 patients
      at the end of each phase of treatment. We repeated symptom-limited treadmill test
      like above method in 15 patients at 7 months of medication. RESULTS: (1)
      Ventricular rates were significantly reduced in digoxin with low-dose betaxolol
      therapy at rest and during exercise (67 +/- 3, 135 +/- 5 (mean +/- S.E.M.)
      beats/min, respectively) in comparison to digoxin with low-dose diltiazem therapy
      (80 +/- 7, 154 +/- 5) (P < 0.05). (2) Rate-pressure products were significantly
      less in digoxin with low-dose betaxolol at rest and during exercise (85 +/- 4,
      213 +/- 12 x 10(2) mmHg/min) than in digoxin with low-dose diltiazem therapy (105
      +/- 6, 269 +/- 12) (P < 0.05). (3) Exercise capacity was significantly improved
      in digoxin with low-dose betaxolol (9.3 +/- 0.5 METS) or digoxin with low-dose
      diltiazem (9.7 +/- 0.5) in comparison to control state (8.3 +/- 0.5) (P < 0.05).
      (4) At 7 months evaluation, there was no significant difference between at 4
      weeks and at 7 months. (5) Results on 24-h ambulatory ECG showed the same
      findings as on treadmill test. (6) Although side effects occurred more frequently
      in digoxin with low-dose betaxolol therapy, they were minimal and no patient had
      to withdraw medication. Worsening of left ventricular dysfunction was not
      observed. CONCLUSION: Our study suggested that (1) combination therapy of low
      dose betaxolol with digoxin was more superior to low-dose diltiazem with digoxin
      in controlling ventricular rate and reducing rate-pressure products; (2) the
      effects controlling ventricular rate, reducing rate-pressure products and
      improving exercise capacity have been well maintained even after 7 months of
      medication with each combination therapy.

PMID- 8749879
TI  - Sinus tachycardia and J wave masquerading as atrial flutter.
AB  - The admission electrocardiogram (ECG) from a patient with severe heart failure
      was considered diagnostic of atrial flutter with 2:1 atrioventricular conduction.
      Slowing of the heart rate revealed sinus tachycardia with prominent 'J' waves
      that had been previously thought to be 'F' waves.

PMID- 8749880
TI  - Effects of disopyramide on the atrial fibrillation threshold in the human atrium.
AB  - The effects of disopyramide on the atrial fibrillation threshold (AFT) in the
      human atrium were investigated. To evaluate atrial vulnerability, the following
      electrophysiologic parameters were measured before and after the administration
      of disopyramide (2 mg/kg) in 12 patients with paroxysmal atrial fibrillation: The
      right atrial effective refractory period (ERP) and percentage maximum atrial
      fragmentation (%MAF) were measured by atrial premature stimulation based on a
      cycle length of 500 ms. The inter-atrial conduction time (ACT) was measured by
      burst pacing (120/min) for 30 s. AFT was measured by applying a high-frequency
      (50 Hz) stimulation for 1 s given at the right atrial appendage. AFT was defined
      as the lowest intensity of electrical current that could induce atrial
      fibrillation lasting for more than 30 s. Disopyramide significantly reduced %MAF,
      and prolonged ERP and ACT. AFT was measured in all patients and the mean AFT was
      3.1 +/- 1.7 mA. After the administration of disopyramide, AFT significantly
      increased to 6.1 +/- 3.6 mA. There was a positive correlation between ERP and
      AFT, and a negative correlation between %MAF and AFT. No correlation was detected
      between ACT and AFT. In conclusion, disopyramide increased AFT in the human
      atrium.

PMID- 8749881
TI  - Prodromal symptoms of relapse in schizophrenia: a review.
AB  - It is often stated that there are identifiable prodromal symptoms of psychosis in
      patients suffering from schizophrenia. In this article, we review the evidence
      for the existence of such prodromal symptoms. Computerized and direct searches of
      the psychiatric literature were conducted to identify relevant reports. The
      methods and findings of the studies were then examined for their relevance to
      several issues concerning prodromal symptoms. We found that very few studies have
      directly assessed the relationship between putative prodromal symptoms and the
      exacerbation of psychosis. The research that has been reported suggests that
      prodromal symptoms have only modest power as predictors of relapse. It appears
      that while some individual schizophrenia patients may show reasonably consistent
      patterns of prodromal symptoms, such symptoms are probably of limited general
      value in predicting psychosis. Two particular issues that warrant further
      investigation are individual differences in patterns of prodromal symptoms and
      the extent to which such symptoms actually precede changes in level of psychosis.

PMID- 8749882
TI  - Prodromal symptoms and relapse prevention in schizophrenia.
AB  - The value of monitoring for prodromal symptoms in patients with schizophrenia has
      been questioned by some investigators who point out that their positive
      predictive value, sensitivity, and specificity can be low in relation to relapse.
      This article focuses on methodological and conceptual issues which should be
      considered in evaluating the usefulness of prodromal symptoms and behaviors as
      part of the relapse process. The article presents the following conclusions: Many
      relapses are preceded by the appearance of prodromal symptoms and behaviors which
      may last from a few days to a few weeks or more. The presence of prodromal
      symptoms often does not predict impending relapse since the probability of
      progression to relapse depends on the complex interaction of many personal and
      environmental factors including the availability of prompt and effective
      psychiatric intervention. Finally, studies have shown that monitoring for
      prodromal symptoms and early intervention when they emerge is effective in
      reducing the likelihood of relapse in individuals with schizophrenia.

PMID- 8749883
TI  - Prodromal symptoms vs. early warning signs and clinical action in schizophrenia.
AB  - The term "prodromal symptoms" has traditionally referred to prepsychotic changes
      in thought, affect, and cognition that precede the initial onset of
      schizophrenia. Recently, however, the term has been extended into a clinical
      action context to refer to the early warning signs (EWS) of impending relapse in
      patients already diagnosed as having schizophrenia. However, recent reports
      reviewed by Norman and Malla (1995, this issue) use a narrow definition of
      prodromal symptoms and question their use in the clinical action context. We
      argue that the dual use of the term "prodromal symptoms" has led to conceptual
      confusion and to the impression that EWS cannot be used effectively for clinical
      action. The ability to base clinical action on EWS is central to schizophrenia
      therapeutics and is the cornerstone of pharmacological strategies based on early
      intervention. Our review of the evidence suggests that the effective clinical use
      of EWS depends on (1) the inclusion of both psychotic and nonpsychotic symptoms
      as EWS; (2) the use of clinician judgment in combination with predefined symptom
      changes to define the occurrence of EWS; (3) frequent clinical visits; and (4)
      the use of family or caregiver informants. We therefore suggest that, in the
      clinical action context, the terminology "early warning signs of impending
      relapse" should be used instead.

PMID- 8749884
TI  - Schizophrenia: treatment outcomes research--editors' introduction.
AB  - Considerable research over the past few decades on the nature and treatment of
      schizophrenia has yielded important advances to improve the outcomes of this
      disorder. Recent action plans, including the "Decade of the Brain," the National
      Institute of Mental Health (NIMH) A National Plan for Schizophrenia Research, and
      NIMH's report, Caring for People With Severe Mental Disorders: A National Plan of
      Research to Improve Services, promise major new advances over the next several
      years. As research advances, it is critical to ensure that patients in everyday
      practice receive the most effective treatments being developed. This issue of the
      Schizophrenia Bulletin reviews the research on outcomes of treatments for
      schizophrenia and lays out an agenda for available research knowledge to be
      translated into practice and for future research to improve outcomes.

PMID- 8749885
TI  - Conventional antipsychotic medications for schizophrenia.
AB  - This article reviews the existing evidence for the efficacy and effectiveness of
      conventional antipsychotic medications in the treatment of schizophrenia. Among
      the issues reviewed are their efficacy for acute symptom episodes and for long
      term maintenance therapy, differential efficacy among medications, the gap
      between research-based efficacy rates and effectiveness rates in practice, dosing
      strategies, and the treatment of first-episode cases. Evidence for efficacy is
      overwhelming for reduction of positive symptoms but quite limited for other
      outcomes. Effectiveness in practice may be substantially less than efficacy in
      clinical trials, perhaps owing to patient heterogeneity, prescribing practices,
      and noncompliance. First-episode patients should be treated with antipsychotic
      medication, but perhaps at lower dosages, with consideration of a gradual
      decrease or discontinuation at 6 months to 1 year.

PMID- 8749886
TI  - Clozapine: efficacy and safety.
AB  - Clozapine (Clozaril) represents the first major advance in the pharmacological
      treatment of schizophrenia since the introduction of antipsychotics into clinical
      practice in the 1950s. Studies consistently support its efficacy for reducing
      positive symptoms in acutely psychotic patients and in treatment-resistant
      patients, for preventing positive symptom exacerbations as a maintenance
      treatment, and for reducing symptoms of hostility and violence. There is evidence
      to suggest that clozapine may improve social and occupational functioning and
      quality of life and may reduce affective symptoms, hospitalizations, secondary
      negative symptoms, and tardive dyskinesia. Its most significant side effects
      include agranulocytosis, seizures, weight gain, hypotension and tachycardia,
      sedation, and perhaps rebound psychosis (with abrupt discontinuation of
      medication).

PMID- 8749887
TI  - Risperidone: efficacy and safety.
AB  - This article reviews the evidence for the efficacy and effectiveness of
      risperidone in persons with schizophrenia. Nine published double-blind studies
      compare risperidone with another antipsychotic medication and/or placebo. All
      were conducted in the acute phase of illness. Risperidone's antipsychotic
      efficacy is shown to be consistently superior to that of placebo and at least
      comparable to that of haloperidol and perphenazine for patients in the acute
      phase of schizophrenia. Further research is necessary to determine the
      effectiveness of risperidone and its efficacy both as a maintenance treatment and
      in treatment-refractory and deficit-state patients.

PMID- 8749888
TI  - Adjunctive treatments in schizophrenia: pharmacotherapies and electroconvulsive
      therapy.
AB  - Substantial proportions of patients with schizophrenia do not achieve acceptable
      levels of response with antipsychotic therapy alone, which commonly leads
      clinicians to use additional somatic interventions. This article reviews the
      literature on the use of adjunctive pharmacological treatments and
      electroconvulsive therapy (ECT) in schizophrenia. The authors find that, despite
      a large volume of literature, it is difficult to draw conclusions or treatment
      recommendations from available data because of small sample sizes and widely
      divergent study designs. At present, there is little firm evidence that adding
      adjunctive agents to standard neuroleptics will dramatically change the somatic
      treatment of schizophrenia. The most promising adjunctive agents are
      benzodiazepines, lithium, and carbamazepine, as well as antidepressants and ECT
      for affective symptoms. Future inpatient research on adjunctive treatments should
      be multicenter studies, followed by long-term outpatient trials that assess
      quality-of-life issues as well as symptom relief.

PMID- 8749889
TI  - Psychological interventions for schizophrenia.
AB  - This review examines the impact of dynamic and supportive psychotherapies (both
      individual and group) and psychosocial skills training on clinical and social
      outcomes for individuals with schizophrenia. The relatively few controlled trials
      of individual or group psychotherapies for persons with schizophrenia exhibit
      serious methodological problems that limit their generalizability. Reality
      oriented approaches appear to be superior to dynamic, insight-oriented
      psychotherapies, but further research is needed to identify and evaluate disorder
      specific models that target specific deficits and disabilities in schizophrenia.
      Research on psychosocial skills training models shows that target skills can be
      trained and maintained over time. Further work is needed to determine the extent
      to which trained skills generalize from the original training setting to "real
      life" environments.

PMID- 8749890
TI  - Family interventions for schizophrenia.
AB  - This article reviews the existing evidence for the efficacy and effectiveness of
      psychoeducational family interventions in the treatment of persons with
      schizophrenia. There is substantial evidence that psychoeducational family
      interventions reduce the rate of patient relapse. There is suggestive, though not
      conclusive, evidence that these interventions improve patient functioning and
      family well-being. Interventions with multifamily groups that include the patient
      may be of superior benefit for subgroups of patients. More research is necessary
      to determine the critical ingredients of family interventions, to expand the
      groups of patients included in these studies, and to evaluate a broader range of
      outcomes.

PMID- 8749891
TI  - Vocational rehabilitation in schizophrenia.
AB  - Schizophrenia exacts a heavy toll on a person's capacity to work, and a variety
      of vocational rehabilitation interventions have been developed over the past few
      decades to enhance the vocational capacities of persons with this disorder. The
      research literature on outcomes of vocational rehabilitation during the era of
      deinstitutionalization for persons with schizophrenia is reviewed. Most
      vocational rehabilitation programs have a positive influence on work-related
      activities, but most have failed to show substantial and enduring impacts on
      independent, competitive employment. Recent advances in supported employment
      suggest that vocational rehabilitation offers greater promise than do
      transitional and sheltered employment approaches. Vocational rehabilitation
      intervention may also exert positive influences on such clinical outcomes as
      medication compliance, symptom reduction, and relapse.

PMID- 8749892
TI  - Assertive community treatment and case management for schizophrenia.
AB  - This review examines the impact of assertive community treatment (ACT) and case
      management models on the use of inpatient hospitalization and other community
      mental health services, costs, and other clinical and social outcomes. ACT
      programs have been found to reduce hospitalization and increase use of community
      mental health services at an equivalent or reduced cost. Greater fidelity to the
      ACT model produced better outcomes. The impact of case management models is less
      consistent, but intensive case management programs also have been found to reduce
      hospitalization. We discuss limitations in past research and recommend future
      directions.

PMID- 8749893
TI  - Treatment outcomes in schizophrenia: implications for practice, policy, and
      research.
AB  - Outcomes research on treatments for schizophrenia has identified a number of
      efficacious interventions. The degree to which such scientific knowledge
      influences the care delivered in everyday practice depends on a large number of
      patient, practitioner, service system, and other social factors. The current
      atmosphere for change in the health care delivery system poses both risks and
      opportunities to improve care for persons with this disorder. Scientific
      knowledge about treatment outcomes must inform this rapid evolution of practice,
      policy, and research to ensure that effective treatments are preserved and
      available for all who need them and that new treatments continue to be developed,
      evaluated, and disseminated.

PMID- 8749894
TI  - Speech and language disorders in children and adolescents with schizophrenia.
AB  - This study examines communication characteristics and specific language deficits
      in 47 children and adolescents diagnosed with early-onset schizophrenia using DSM
      III-R criteria. All had been referred for speech and language services because of
      apparent communication problems. Standardized tests and formal measures were used
      to identify impairment in discrete areas of communication, including pragmatics,
      receptive and expressive vocabulary and syntax, abstract language, auditory
      processing, and speech production. Results showed that these discrete areas were
      variably involved, with pragmatics, prosody, auditory processing, and abstract
      language having the greatest involvement. The communication deficits identified
      in the early-onset group closely resembled the phenomenology reported in studies
      of the communication characteristics of adults with schizophrenia. This
      comparison thus lends further support to the presence of the same disorder as
      seen in adults. The roles of gender, mental retardation, and seizure disorders
      are also discussed as additional risk factors in the development of communication
      problems and schizophrenia.

PMID- 8749895
TI  - Maintenance medication for schizophrenia and schizoaffective patients.
AB  - This study assesses the different approaches to treating patients with
      schizoaffective and paranoid schizophrenia in remission. Individualized treatment
      of 220 outpatient schizophrenia patients was conducted for 4 years. The choice of
      treatment was based on the course of the disease and the frequency of relapses.
      The influence of changes in treatment on the patterns of relapses is presented.
      The results of this prospective followup open study were evaluated by comparing
      data received during our research with data from the two preceding 4-year periods
      and with data from the control group. Compared with routine methods, special
      treatment tactics led to a significantly decreased frequency of relapses in
      patients with frequent relapses (p < 0.001). In patients with rare relapses, full
      cessation of treatment did not lead to increasing mean frequency of relapses.
      Treatment in remission should be based on the peculiarities of the course of
      disease, specifically, frequency of relapses, type of schizophrenia, and presence
      or absence of positive psychopathological signs in remission.

PMID- 8749896
TI  - First person account: insight from a schizophrenia patient with depression.

PMID- 8749897
TI  - General aspects of drug-induced liver disease.
AB  - Medicinal agents can produce various types of hepatic injury by several
      mechanisms. Hepatic injury may lead to acute syndromes that resemble viral
      hepatitis, fatty liver of pregnancy, and obstructive jaundice, as well as to a
      number of chronic syndromes. Acute liver damage relates, at least in part, to the
      apparent mechanism of injury. Hepatic injury induced by large single overdose of
      intrinsically toxic drugs (e.g., acetaminophen, ferrous salts) develops within 24
      to 72 hours of intake and usually is accompanied by renal failure. Regular intake
      of some toxic drugs, (e.g., methotrexate) leads to slowly evolving chronic
      disease. Liver damage due to hypersensitivity-type idiosyncrasy usually appears
      after 1 to 5 weeks of taking the drug unless there has been previous exposure and
      is preceded or accompanied by systemic features that are hallmarks of
      hypersensitivity. Hepatic injury attributable to metabolic idiosyncrasy may
      appear after weeks to months of taking the drug and usually presents without the
      systemic features. Organs other than the liver may be involved in the syndrome of
      drug-induced injury as the result of selective injury or as part of a
      hypersensitivity reaction.

PMID- 8749898
TI  - Morphologic spectrum of drug-induced hepatic disease.
AB  - This article reviews the spectrum of pathologic changes in the liver induced by
      drugs and toxins. These resemble, and are often indistinguishable from, similar
      lesions from different origins. The changes are described briefly and examples
      are illustrated by photomicrographs from the files of the Armed Forces Institute
      of Pathology.

PMID- 8749899
TI  - Mechanisms of drug-induced liver disease.
AB  - The liver is the main metabolizing organ in the body for drugs and toxins. The
      liver is therefore exposed to relatively high levels of electrophilic metabolites
      and free radicals that may induce toxicity. Furthermore, the liver performs many
      vital functions that may be disrupted by toxic metabolites. Despite the high
      exposure to reactive metabolites, drug-induced toxicity is relatively uncommon
      because of the redundancy of the detoxification systems present in the liver.

PMID- 8749900
TI  - Genetic predisposition to drug-induced liver disease.
AB  - Rarely do otherwise safe drugs administered at recommended doses produce liver
      damage that may progress to liver failure and death. Because we are generally
      unable to identify the patients most susceptible to this "idiosyncratic" form of
      toxicity, many potentially useful medications are not made available to patients.
      The most promising developments in identifying susceptible patients have stemmed
      from recent advances in characterization of bioactivation and detoxification
      enzyme systems, and the discovery of marked variation in the activities of these
      enzymes among patients. Tests capable of quantitating the activities of specific
      relevant enzymes have been recently developed and are now being applied in
      clinical trials to assess risk factors for drug-induced liver disease. These
      tests hold promise of identifying subsets of patients who may need close
      monitoring or who may be best served with an alternate treatment.

PMID- 8749901
TI  - Hepatotoxicity of antiviral agents.
AB  - Because most therapeutic agents used for viral infections are relatively new,
      experience with their adverse effects is still evolving. Hepatic toxicity has not
      been among the most important concerns with this class of drugs so far. Liver
      damage has been increasingly noted with accumulating experience, especially with
      antiretroviral drugs and those used to treat chronic hepatitis (e.g.,
      fialuridine), but it is often difficult to distinguish between effects of therapy
      and of the underlying disease. It is important for clinicians to be aware of the
      possibility of hepatotoxicity in such situations, and further reporting of
      adverse experiences should contribute to more definitive evaluation of the
      potential influence of antivirals on liver function.

PMID- 8749902
TI  - Hepatotoxicity of anesthetics and other central nervous system drugs.
AB  - A large number of anesthetics, tranquilizers, hypnotic sedatives, and
      anticonvulsants are used clinically. Although these agents are generally well
      tolerated, liver injury of differing patterns is well recognized with their use.
      Knowledge of the likelihood of hepatotoxicity and the characteristic clinical
      features with these compounds is important as fatal outcomes due to liver failure
      have been reported with several of these agents. This article describes the
      potential mechanisms and clinical features of drug hepatotoxicity associated with
      these compounds.

PMID- 8749903
TI  - Hepatotoxicity of analgesics and anti-inflammatory agents.
AB  - Nearly all analgesic and anti-inflammatory agents have the potential for hepatic
      injury. Most nonsteroidal anti-inflammatory drugs (NSAIDs) produce injury in an
      unpredictable fashion by way of an idiosyncratic (immunologic versus metabolic)
      mechanism, whereas acetaminophen and aspirin are more predictable because they
      produce injury in a dose-dependent manner by way of intrinsic toxicity. Both
      acetaminophen and aspirin may produce hepatotoxicity despite therapeutic intent.
      This article discusses specific NSAIDs available in the United States and abroad
      and their associated hepatotoxicity and carefully considers acetaminophen-related
      hepatotoxicity reviewing risk factors for injury, clinical features, prognosis,
      and management.

PMID- 8749904
TI  - Hepatotoxicity of anticholesterol, cardiovascular, and endocrine drugs and
      hormonal agents.
AB  - Drugs in these categories may have effects on several organs in addition to the
      liver. For example, amiodarone may produce thyroid and corneal injury apart from
      or in addition to the phospholipidosis seen in the liver. Oral contraceptive
      steroids remain a rare but important concern for developing hepatic adenomas and
      possibly hepatocellular carcinoma, as well as a risk factor for developing Budd
      Chiari syndrome in long-term users. Among the antihyperlipidemic agents,
      nicotinic acid, especially the sustained release formulations, may produce severe
      of even fatal hepatic injury. Increasing numbers of reports of hepatotoxicity
      from newer beta blockers and angiotensin-converting enzyme inhibitors require
      ongoing vigilance in patients receiving these medications.

PMID- 8749905
TI  - Hepatotoxicity of antimicrobial, antifungal, and antiparasitic agents.
AB  - Several antibiotics are known to be hepatotoxic. Apart from subtle, reversible,
      and often inconsequential abnormalities, cholestasis is the predominant
      presentation that has a protracted and disabling course. Hepatitis, like illness,
      is characteristic of some drugs, and chronic liver disease may evolve. It is
      important to recognize if a patient has an adverse reaction to a drug because
      continuing use of the drug in the face of hepatitis can have disastrous
      consequences. Chronic liver disease may ensue and progress onto cirrhosis; this
      has typically been seen following use of isoniazid and nitrofurantoin.
      Cholestatic liver disease can progress into a chronic form of a ductopenic state;
      this is particularly seen after antibiotic-related cholestasis.

PMID- 8749906
TI  - Hepatotoxicity of drugs used in the treatment of gastrointestinal disorders.
AB  - Hepatic injury from agents in this category is rare. For example, only a handful
      of cases of H2-receptor antagonist-related liver injury have been reported
      despite the hundreds of millions of doses prescribed since the introduction of
      these drugs more than 15 years ago. Hepatotoxicity from sulfasalazine is uncommon
      but may be fatal. Injury from other agents used to treat inflammatory bowel
      disease also may be seen, including veno-occlusive disease from azathioprine. Of
      increasing importance is the toxicity from alternative health supplements, such
      as herbal remedies, that may cause acute, sometimes fatal, hepatic necrosis.

PMID- 8749907
TI  - Hepatotoxicity of chemotherapeutic and oncologic agents.
AB  - Problems arise in cancer chemotherapy when liver function tests are not normal,
      when drugs that possess known hepatic toxicity are to be given, and when
      abnormalities arise after drug administration. Most hepatotoxic drug reactions
      are idiosyncratic, occuring because of either hypersensitivity mechanisms or host
      metabolic idiosyncrasy. The clinician must always consider that liver injury is
      due to an idiosyncratic drug reaction, especially in a setting where patients
      typically receive many drugs, such as an oncology service. Chemotherapeutic
      agents often possess predictable, dose-dependent ("direct") hepatotoxicity,
      however. This article addresses the spectrum of hepatotoxic effects of
      chemotherapeutic agents. The hepatotoxic potential of single-agent as well as
      combination chemotherapy is discussed and recommendations for dose modifications
      in patients with impaired hepatic function are provided.

PMID- 8749908
TI  - Hepatotoxicity of transplant immunosuppressive agents.
AB  - Hepatotoxicity from transplant immunosuppressive agents is infrequent but
      recognized. Most of the published literature emphasizes hepatotoxicity from
      cyclosporine and azathioprine. Cyclosporine is associated with cholestasis and
      possibly biliary calculi. Azathioprine has been associated with a variety of
      hepatic abnormalities. This article reviews the frequency and pattern of
      hepatotoxicity associated with these agents.

PMID- 8749909
TI  - Hepatobiliary toxicity of total parenteral nutrition in adults.
AB  - The enzymology and clinical manifestations of total parenteral nutrition (TPN)
      induced liver abnormalities have been investigated extensively. The cause,
      pathogenesis, and treatment of TPN-related hepatic and biliary dysfunction in
      adults still are not well understood, however. The findings of experimental
      studies in animals has not necessarily correlated with the human data, and there
      have been few prospective, randomized controlled trials examining the mechanism,
      cause, or treatment of TPN-induced hepatobiliary toxicity in adults. This article
      examines the animal models of pathogenesis and treatment of TPN-induced
      intrahepatic and extrahepatic abnormalities, and provides a discussion of
      abnormalities seen in humans.

PMID- 8749910
TI  - Chemical- and toxin-induced hepatotoxicity.
AB  - Hepatic injury due to chemicals or natural toxins may occur from occupational,
      household, or environmental exposure. The liver may dominate the syndrome of
      toxicity from such agents as carbon tetrachloride, poison mushrooms, and toxic
      alkaloids, or may be only one facet of more generalized toxicity. The entire
      histologic spectrum of injury, from fulminant acute disease to chronic vascular
      injury to hepatic neoplasia, is seen with agents in this category.

PMID- 8749911
TI  - Prevention and treatment of drug-induced liver disease.
AB  - Many drugs may cause liver damage; some damage is predictable, but most is not.
      The most important preventive measure is judicious drug use by the prescribing
      physician. Early recognition of hepatotoxicity and cessation of the offending
      agent is essential for treatment. The best example of a specific treatment for
      drug-induced liver disease is N-acetylcysteine treatment for acetaminophen
      hepatotoxicity. Many examples are cited of other attempts at treatment in animal
      models of drug-induced liver disease. If drug-induced liver disease leads to
      fulminant hepatic failure, intensive management of the resulting complications is
      required. Liver transplantation may be the only treatment option.

PMID- 8749912
TI  - Selective surgical management of progressive familial intrahepatic cholestasis
      (Byler's disease).
AB  - Progressive familial intrahepatic cholestasis (PFIC) presents in early childhood
      with pruritus, jaundice, hepatomegaly, and growth failure. Medical therapy is
      unsuccessful, with progression from cholestasis to hepatic fibrosis, cirrhosis,
      and ultimately death before the age of 10 years. Because of evidence that biliary
      diversion can arrest or reverse progression to hepatic fibrosis, we have used
      partial biliary diversion (PBD) as primary therapy in PFIC, reserving orthotopic
      liver transplantation (OLT) for children who have progressive disease or
      established cirrhosis. Seventeen children with PFIC (aged 2 months to 19 years)
      have been treated. PBD was performed in eight cases. In these procedures, a 10-cm
      properistaltic jejunal segment was anastomosed to the side of the gallbladder,
      terminating as an end stoma for the collection and discard of bile. Eleven
      patients with hepatic insufficiency (or end-stage cirrhosis) received OLT using
      standard techniques, at the average age of 4 years. Six of the eight children
      treated with PBD had complete resolution of clinical symptoms and remain well 1
      to 13 years postoperatively. These six patients have conjugated bilirubin values
      of less than 0.3 mg/dL, normal transaminases, and a serum bile salt concentration
      of less than 10 nmol/mL. All have had either reversal or no progression of the
      hepatic fibrosis. Postoperative bleeding complications occurred in two (25%),
      which required reoperation. One patient had an adhesive intestinal obstruction
      that was managed surgically 9 months postoperatively. Two patients had no benefit
      from PBD, and all of them had severe bridging fibrosis (1) or cirrhosis (3).
      These and nine others with cirrhosis at the time of presentation received
      orthotopic liver transplantation; of these, eight are alive (1 to 5 years
      postoperatively). These results show the importance of establishing a correct
      diagnosis in children with cholestasis. Clinical symptoms often are severe in
      children with PFIC before the development of irreversible hepatic fibrosis.
      Because several patients who appear to have been cured with PBD initially were
      scheduled for OLT, it is important that transplant surgeons recognize the
      feasibility of this approach.

PMID- 8749913
TI  - Laparoscopic and thoracoscopic assistance with CSF shunts in children.
AB  - Between June 1992 and June 1994, six children underwent laparoscopic or
      thoracoscopic assistance in the management of cerebrospinal fluid (CSF) shunts.
      Four children (3 to 12 years of age) required laparoscopic assistance. Two
      children (5 and 10 years of age) underwent thoracoscopy with insertion of
      syringopleural shunts for decompression of cervicothoracic hydromyelia. Most
      children who require CSF decompression do not need endoscopic assistance for
      placement of the terminal portion of the shunt. However, in selected patients who
      have undergone previous abdominal procedures, in patients with a persistent
      pseudocyst occupying an extensive portion of the abdominal cavity, and in
      patients requiring removal of a disconnected shunt, laparoscopy is the ideal
      approach. Thoracoscopy for a syringopleural shunt prevents the need for
      minithoracotomy.

PMID- 8749914
TI  - Posttraumatic peritoneal fluid: is it a reliable indicator of intraabdominal
      injury in children?
AB  - Clinical data and computed tomographic (CT) scans for 1,486 children evaluated
      after blunt abdominal trauma were reviewed to determine whether peritoneal fluid
      is a reliable indicator of the presence and severity of associated intraabdominal
      injury and the need for laparotomy. The CT scans were assessed for presence,
      location, and severity of intraabdominal injury, and amount of peritoneal fluid.
      Type of management (surgical or nonsurgical), indications for surgical
      management, overall hospital course, and clinical outcome were recorded at the
      time of discharge. Of the 326 children with abdominal injuries detected by CT,
      121 (37%) had no associated peritoneal fluid collections. Eighteen (15%) of these
      children had injury to more than one abdominal organ. Splenic injuries by CT
      criteria were more severe in children with associated peritoneal fluid than in
      those with no associated fluid (P < .003). There were no significant differences
      in CT grading of liver and renal injuries among those with and without associated
      peritoneal fluid (P > .67). Two hundred fifty-nine (17%) of the 1,486 children
      had peritoneal fluid demonstrated by CT. Eighty percent of these children had
      concomitant intraabdominal injury. Associated injuries included solid organ
      injuries (in 68% of patients) hollow viscus or mesenteric injury (11%), isolated
      pelvic fracture (4%), and hypoperfusion syndrome (5%). Thirty-one patients (12%)
      had injury to more than one abdominal organ. Only 27 (11%) patients had small
      "unexplained" collections of peritoneal fluid in which no associated injury was
      detected through CT or clinical follow-up. The authors conclude that (1) solid
      organ injury is frequently present in the absence of peritoneal fluid, and (2)
      the identification of peritoneal fluid after blunt trauma should lead one to
      suspect that a specific intraabdominal injury is the cause of the fluid.

PMID- 8749915
TI  - Aggregatory characteristics and expression of the collagen adhesion receptor in
      fetal porcine platelets.
AB  - Fetal wound healing differs significantly from that of the adult by its rapidity,
      the paucity of an inflammatory response, and the lack of scarring. In the adult,
      activation and aggregation of platelets at the site of injury result in the
      release of cytokines and inflammatory mediators that stimulate wound healing by
      initiating an acute inflammatory response. The aim of this study was to
      characterize the activity of midtrimester (day 60) and third-trimester (day 95)
      fetal porcine platelets (full term, 114 days) compared with that of adults in an
      attempt to understand the lack of inflammation in fetal wounds. The aggregatory
      capabilities of adult and fetal platelets were analyzed after exposure to
      adenosine diphosphate (ADP) concentrations of 10 mumol/L and 40 mumol/L
      concentrations, collagen of 0.19 mg/mL, and arachidonic acid of 0.5 mg/mL.
      Expression of the alpha 2 subunit of the collagen receptor (alpha 2 beta 1) was
      evaluated by Western blot analysis. The aggregation of day-60 fetal platelets
      when exposed to ADP (10 mumol/L and 40mumol/L) and collagen was significantly
      lower than that of the adult. The aggregation of third-trimester platelets to 10
      mumol/L of ADP was similar to that of the adult and significantly greater than
      that of midtrimester fetuses at higher concentrations (40 mumol/L). Both fetal
      groups responded suboptimally to collagen, and the response was significantly
      less than that of adults. In contrast, arachidonic acid caused rapid and complete
      aggregation of both fetal platelet groups, suggesting that both mid- and late
      trimester fetal platelets possessed the ability to fully aggregate with the
      appropriate stimulus. The different aggregatory responses to collagen could not
      be explained by differences in collagen receptor expression, because these were
      found to be similar in adults and midtrimester fetuses. It is concluded that
      although fetal platelets have the potential to aggregate effectively, they
      aggregate poorly to collagen and exhibit improved aggregation to ADP with
      increasing maturity. There is a transition to "adultlike" platelet aggregatory
      activity in the third trimester, which correlates with the period of transition
      to adultlike wound healing in utero. Similar expression of the alpha 2 beta 1
      collagen receptor in the fetus and adult cannot explain the differences observed
      in their responses to collagen.

PMID- 8749916
TI  - Neovascularization of the testicle through spermatic vessels by omental pedicle
      flap: a new experimental model.
AB  - The aim of this experimental study in rats was to consider the supplementary role
      of an omental pedicle flap on the neovascularization of the testicle through the
      spermatic vessels, for which a Fowler-Stephens procedure had been planned. To
      compare results, 12 animals had only the spermatic vessels ligated, without an
      additional procedure (Fowler-Stephens procedure [FS group]), and 12 others had
      omentopexy of the spermatic vessels of the left testes, with ligation of the
      vessels 4 weeks later (Fowler-Stephens procedure plus omentopexy [FSO group]). In
      the sham group (n = 8), only omentopexy of the left spermatic vessels was
      performed. Six rats served as controls. In each rat, both testes were evaluated
      by color Doppler ultrasonography to assess capsular and intratesticular blood
      flow, followed by orchiectomy to determine testicular weights, testicular biopsy
      scores, and mean seminiferous tubule diameters. Data were analyzed statistically.
      According to the color Doppler ultrasonography, the testicular blood flow in the
      FSO group was better than that of the FS group, but was less sufficient than that
      of the sham and control groups. The testicular weights and biopsy scores for the
      FSO group were statistically greater than those of the FS group, and less than
      those of the sham and control groups. There was no significant difference in the
      mean seminiferous tubule diameters of the FSO and FS groups. The contralateral
      tests of the four groups did not differ significantly for any parameter. In light
      of the data available, it is suggested that the omental pedicle flap
      neovascularizes the testicle through spermatic vessels. Given the high incidence
      of testicular atrophy associated with Fowler-Stephens orchiopexies, it might be
      beneficial to perform laparoscopic orchiopexy of testicles neovascularized with
      omental pedicle flaps as the first-stage procedure.

PMID- 8749917
TI  - Pancreaticobiliary maljunction without choledochal cysts in infants and children:
      clinical features and surgical therapy.
AB  - Pancreaticobiliary maljunction (PBM) usually is associated with choledochal cyst.
      PBM without dilatation of the common bile duct is rare in infants and children.
      This rare type of the anomaly may lead to the development of malignancy of the
      bile duct in later life. The authors report the clinical presentation and
      surgical treatment of seven pediatric patients with PBM. Symptoms and signs
      included repeated episodes of abdominal pain (7 of 7), nausea and vomiting (6 of
      7), intermittent jaundice (3 of 7), and acholic stools (2 of 7). Some patients
      presented with high levels of serum and urinary amylase. These symptoms and signs
      might have been related to the temporary obstruction of bile flow in the common
      channel, where endoscopic retrograde cholangiopancreaticography (ERCP) disclosed
      a protein plug in four of the patients. The common bile duct proximal to the
      junction of the main pancreatic duct was excised, and a Roux-en-Y
      hepaticojejunostomy reconstruction was performed. To prevent iatrogenic injury of
      the main pancreatic duct, repeat cholangiography was performed with the aid of
      radiopaque silver clips placed on the line of dissection to evaluate the distance
      between the site of dissection and the main pancreatic duct. All patients have
      been free of symptoms since the surgery. PBM without dilatation of the common
      bile duct can be detected more frequently if ERCP is performed on every patient
      who has repeated episodes of abdominal pain refractory to conventional therapy.
      Complete excision of the common bile duct and gallbladder followed by
      hepaticojejunostomy is recommended for PBM, while the goals of decreasing the
      high risk of carcinoma of the bile duct and preventing recurrent symptoms.

PMID- 8749918
TI  - The morphology of the contralateral internal inguinal rings is age-dependent in
      children with unilateral inguinal hernia.
AB  - The contralateral internal inguinal rings of 333 children were examined with a
      laparoscope during repair of unilateral inguinal hernia. The nonpuncture
      laparoscopy technique was used so that no extra wound was created. The morphology
      of the rings was classified as follows: type 1, flat and covered tightly with
      peritoneum; type 2, shallow with a visible base under an elevated peritoneal
      fold; type 3, deep ring that represented a patent processus vaginalis. The
      incidence of types 1, 2, and 3 rings was 45%, 23%, and 32%, respectively. The
      incidence of type 1 internal rings was similar for different age groups. The
      incidence of type 2 rings increased with age, and that of type 3 decreased with
      age. This observation is compatible with autopsy studies and the experience of
      contralateral exploration of childhood inguinal hernias.

PMID- 8749919
TI  - Bilateral ureteral obstruction after appendectomy in children.
AB  - Five cases of bilateral ureteral obstruction after appendicectomy are presented.
      All five patients were boys (age range, 9 to 15 years). All of them had had
      severe appendicitis. Based on the urethrocystoscopy findings, edema of the
      posterior bladder wall appeared to be the cause of obstruction of both distal
      ureters. This is confirmed by the immediate recovery of renal function after
      installation of bilateral uretercatheters. It is known that contamination of the
      peritoneal cavity can occur by organisms leaking from a gangrenous or perforated
      appendix. This can cause localized inflammatory edema of the posterior bladder
      wall. It is remarkable that through ultrasound investigation, only mild to
      moderate dilatation of the urinary tract was observed. An explanation can be
      obtained from animal models, wherein acute obstruction of the ureter leads only
      to a transient increase in ureteral pressure, followed by a decline toward the
      preobstruction level. It is important to be aware that this complication can
      occur after appendectomy; bilateral uretercatheters can be installed, and
      irreversible renal damage can be avoided.

PMID- 8749920
TI  - Unique protein expression by the TBJ clonal derivative of C1300 murine
      neuroblastoma.
AB  - C1300 is a murine neuroblastoma that arose spontaneously in an A/JAX mouse, and
      from which a clone termed TBJ was subsequently derived. C1300 is a slowly growing
      and poorly metastasizing tumor, whereas TBJ shows early systemic metastasis as
      well as aggressive local growth. Compared with TBJ cells, C1300 cells are highly
      immunogenic and are sensitive to natural killer cells and cytotoxic lymphocytes.
      In vitro, TBJ cells were found to be more rounded and less adherent than C1300
      cells. Because the underlying basis for the differences between C1300 and TBJ
      cells has not been fully elucidated, the authors used high-resolution two
      dimensional gel electrophoresis (2-DE) to study comparative aspects of total
      protein expression by each cell line. Of the approximately 400 individual
      cellular proteins that could be resolved using this technique, two were found to
      be reproducibly and uniquely expressed by TBJ cells and not by C1300 cells. Both
      proteins were anionic (pl 5.0 to 5.2) as assessed by iso-electric focusing and
      had molecular weights of 76,000 and 82,000 as assessed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). Silver staining of SDS
      polyacrylamide gels showed that the levels of 82,000-M(r) protein (p82) were
      higher than those of the 76,000-M(r) protein (p76). A purification protocol
      allowing for the isolation of p82 from TBJ cell extracts was developed, which
      comprised preparative two-dimensional gel electrophoresis followed by reverse
      phase high-performance liquid chromatography. Full molecular identification of
      p82 and p76 eventually may provide new leads in the study of the metastatic or
      antigenic properties of neuroblastoma.

PMID- 8749921
TI  - Computer-assisted image-guided surgery in pediatric skull-base procedures.
AB  - Skull-base surgery is characterized by the variety of important neural and
      vascular structures within a narrow operating field. Although preoperative
      imaging by computed tomography (CT) and magnetic resonance imaging (MRI) and the
      use of microsurgical techniques have improved intraoperative orientation, a large
      number of complications still are caused by localization problems. Especially in
      pediatric skull-base surgery, maximum localization accuracy during surgery is
      required. The authors developed a localizing system based on tomographic imaging
      (such as CT or MRI) to achieve safer surgery by providing highly accurate
      location information. The preliminary successful experience in the use of the
      Aachen computer-assisted surgery device for pediatric skull-base surgery (14
      cases) is presented. Indication include juvenile angiofibroma of the nasopharynx,
      infectious and tumorous diseases of the paranasal sinuses, orbital tumors,
      foreign bodies, and intracranial abscess formation.

PMID- 8749922
TI  - Male infertility after surgery for imperforate anus.
AB  - Congenital abnormalities of the genitourinary tract often coexist, and
      cryptorchidism is common in patients who have had imperforate anus. Twenty men
      who had pull-through procedures for imperforate anus in infancy have been
      evaluated for infertility. Seven had coexisting renal abnormalities, 4 had had
      recurrent epididymitis, 3 had had bilateral orchidopexies (at age 7 to 12), 2 had
      spina bifida, and 1 had a pituitary adenoma. Seven had no ejaculate (aspermia),
      11 were azoospermic, 1 was severely oligozoospermic, and 1 had a normal sperm
      concentration in a small volume of ejaculate. Both vasa were blocked in 5 men,
      and this appeared to be a result of the original operative procedure. One vas was
      blocked in another 7 patients who had abnormalities on the contralateral side;
      three had epididymal blocks after epididymitis, and four had congenital
      malformations associated with an absent or ectopic kidney. After reconstruction
      (4), insertion of sperm reservoirs (4), microscopic epididymal sperm aspiration
      (2), or artificial insemination (1), sperm were retrieved from 9 men (ejaculated
      by 4) 2 pregnancies occurred. Male infertility after treatment of imperforate
      anus in infancy can be related to a wide variety of cause, some of which are
      amenable to treatment.

PMID- 8749923
TI  - Overexpression of intercellular adhesion molecule-1 (ICAM-1) and MHC class II
      antigen on hypertrophic nerve trunks suggests an immunopathologic response in
      Hirschsprung's disease.
AB  - The pathogenesis of Hirschsprung's disease (HD) is not fully understood. The
      authors studied expression of intercellular adhesion molecule-1 (ICAM-1) and
      major histocompatibility complex (MHC) class II antigen in the resected bowel
      specimens of 18 patients with HD who had no evidence of enterocolitis and in
      eight age- and site-matched controls, using indirect immunohistochemistry. There
      was strong expression of ICAM-1 and MHC class II antigen on hypertrophic nerve
      trunks, in both the submucous and myenteric plexuses of the aganglionic colon.
      The transition zone showed strong expression of ICAM-1 and MHC class II antigen
      on small ganglia in the myenteric and submucous plexuses. However, no staining of
      ganglia or nerve fibers was found in the submucous and myenteric plexuses of the
      colon from controls or in the ganglionic colon from patients with HD. The
      expression of both antigens on hypertrophic nerve trunks suggests the presence of
      an immunologic response in the pathogenesis of HD.

PMID- 8749924
TI  - Unilateral inguinal hernia in girls: is routine contralateral exploration
      justified?
AB  - To determine the incidence of contralateral hernia development after unilateral
      inguinal hernia repair in girls, collected case series from two large hospitals
      were analyzed retrospectively. Among the 294 girls who had analyzed repair of a
      unilateral inguinal hernia (during a 15-year period), 245 could be traced; the
      mean follow-up period was 8.4 years. In 25 (10.2%) of the patients, contralateral
      hernia developed, mostly within one year (4 months to 6.5 years). The incidence
      of contralateral hernia development with respect to the original side of the
      inguinal hernia was significantly higher (19%) for the originally left-sided
      hernias than for the right-sided ones (6%) (P < .01). Although the incidence of
      contralateral hernia development for girls with a left inguinal hernia decreased
      as age increased, it was still 14.9% for the girls age 3 and up. Contralateral
      exploration should not be routine for girls who have a right-sided hernia, at any
      age. For left-sided hernias, it may be performed routinely for girls up to 2
      years of age, and selectively for older patients.

PMID- 8749925
TI  - Abnormal expression and distribution of nidogen in Hirschsprung's disease.
AB  - Hirschsprung's disease (congenital colonic aganglionosis) is associated with
      abnormalities in the distributions and amounts of basement membrane and other
      extracellular matrix components in the human gut. The authors have investigated
      the possible significance of nidogen in Hirschsprung's disease, because this
      glycoprotein is necessary for the formation of ternary complexes with the other
      basement membrane components, laminin and collagen type IV, and thus may
      contribute the pathology of the disease. Increased nidogen immunoreactivity in
      the smooth muscle basement membranes and muscularis mucosae of the distal
      aganglionic zone in Hirschsprung's bowel was observed, the nidogen
      immunoreactivity demonstrating that the thickness of the muscularis mucosae was
      increased in this region. However, steady-state nidogen mRNA levels were found to
      be significantly lower in both proximal and distal Hirschsprung's bowel (relative
      to controls). In contrast, no significant differences were observed in the steady
      state levels of the mRNAs coding for laminin subunits. These results indicate
      that although abnormalities in the amount or distribution of nidogen may
      contribute to the abnormalities seen in the extracellular matrix in
      Hirschsprung's disease, the levels of expression of the genes coding for either
      nidogen or laminin are unlikely to be primarily responsible for the lesions.

PMID- 8749926
TI  - Prognostic indicators in congenital diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia is associated with significant mortality and
      morbidity. The aim of this study was to compare a series of tests with respect to
      prediction of outcome. Tidal volume and compliance of the respiratory system
      (CRS) were measured preoperatively and on the first and second postoperative
      days. The maximum and modified ventilation indexes and the maximum Paco2 were
      noted for the first 6 hours of life and the first 6 hours postoperatively. In
      addition, it was recorded whether the stomach was within the ipsilateral
      hemithorax preoperatively. Twenty infants were studied (median gestational age,
      38 weeks; range, 31 to 40), six of whom had a poor outcome, ie, they died or
      remained oxygen-dependent after 28 days. A CRS of less than 0.18 mL/cm H2O/kg was
      the most accurate predictor of poor outcome, with 66% sensitivity and 100%
      specificity. The authors conclude that lung function measurement are useful in
      the assessment of infants with congenital diaphragmatic hernia.

PMID- 8749927
TI  - Use of the donor iliac vein to replace the retrohepatic vena cava in pediatric
      reduced-size liver retransplantation.
AB  - The authors describe a new technique that used the donor common iliac vein and
      its bifurcation into the external iliac and internal iliac veins to replace the
      retrohepatic vena cava; this was used in a recipient who underwent her second
      reduced-size transplantation (segments II and III). Anastomosis of the donor
      hepatic vein to the internal iliac vein, with use of this segment of the venous
      graft to replace the retrohepatic vena cava, is for patients who have had more
      than one surgical procedure before liver transplantation.

PMID- 8749928
TI  - Primary omental torsion in a 6-year-old girl.
AB  - The case of a 6-year-old girl who was admitted with abdominal pain and diagnosed
      to have primary omental torsion through laparatomy is presented. The presence of
      serosangineous fluid mimicking acute appendicitis but clinically not as bad as
      expected is suggested to raise the suspicion of primary omental torsion.

PMID- 8749929
TI  - Clinical presentation of rare appendiculo-omphalic anomalies.
AB  - The umbilicus is the site of a number of well-recognized and unusual congenital
      anomalies. The authors report two rare anomalies of the umbilicus, one involving
      the appendiceal artery and the other the appendix vermiformis.

PMID- 8749930
TI  - Vertical partial splenectomy for epidermoid cyst.
AB  - Benign lesions of the spleen usually can be surgically removed by partial
      splenectomy. When the lesion is longitudinal and occupies most or the entire
      length of the spleen, partial splenectomy using the common surgical technique,
      based on the distribution of the organ's blood supply, is impossible. A new
      approach for "vertical" partial splenectomy for epidermoid cyst is described,
      using splenic artery occlusion and straight suture needles.

PMID- 8749931
TI  - Familial gastroschisis: a case of mother-and son occurrence.
AB  - Gastroschisis is a rare congenital abdominal wall anomaly with a pathogenesis and
      mode of transmission that are not completely understood. There are few published
      reports of familial gastroschisis and no reported case of vertical transmission.
      The authors report the first published case of a mother who had gastroschisis and
      gave birth to a son with gastroschisis, which supports a genetic etiology.

PMID- 8749932
TI  - Successful left trisegmentectomy for ruptured hepatoblastoma using intraoperative
      transarterial embolization.
AB  - Although surgical treatment with resection for spontaneous rupture of
      hepatoblastoma into the free abdominal cavity is difficult in small children, it
      may be the only treatment available. The authors describe a 16-month-old girl who
      showed a progressive decrease in hematocrit and no response to blood transfusion,
      after spontaneous rupture of a large hepatoblastoma that extended to the pubic
      bone. Percutaneous transcatheter arterial embolization could not be performed
      because selective catheterization was impossible. Therefore, emergency surgery
      was conducted. After intraoperative transcatheter arterial embolization (IOTAE)
      to control hemorrhage, left trisegmentectomy was performed. The patient then
      underwent chemotherapy, followed by autologous bone marrow transplantation. The
      hemorrhage from the ruptured tumor was completely arrested by IOTAE, and the
      postoperative course was uneventful. Hepatic resection after IOTAE, followed by
      chemotherapy and bone marrow transplantation, represents a promising treatment
      for ruptured hepatoblastoma.

PMID- 8749933
TI  - Hepatocellular carcinoma complicating biliary cirrhosis caused by biliary
      atresia: report of a case.
AB  - A case of hepatocellular carcinoma complicating biliary cirrhosis caused by
      biliary atresia is reported. The patient had persistent severe jaundice with
      hepatosplenomegaly. A liver tumor was suspected because of the elevated serum
      alpha-fetoprotein and was shown by ultrasonography at 6 years of age. The tumor
      was treated with percutaneous ethanol injection therapy (PEIT). Nine months after
      initiation of PEIT, the patient died of massive bleeding from a metastatic tumor.

PMID- 8749934
TI  - Delayed separation of an appendix-containing umbilical stump.
AB  - A case of delayed separation of the umbilical cord is reported. Ultrasonography
      and radiographic examination of the stump showed connection with the bowel.
      During surgery the cord was found to contain the appendix. The authors
      hypothesize that this anomaly represents a small omphalocele, resulting from
      failure of the gut to withdraw completely from the umbilical cord, or, less
      likely, a hernia.

PMID- 8749935
TI  - Nonoperative management of biliary tract fistulas after blunt abdominal trauma in
      a child.
AB  - Nonoperative treatment was carried out in a 12-year-old girl who presented with
      biliary fistulas after blunt abdominal trauma with hepatic injury. A computed
      tomography-guided percutaneous puncture showed biliary peritonitis and permitted
      the positioning of an efficient intraperitoneal drainage. Endoscopic retrograde
      cholangiography was very helpful for visualization and accurate localization of
      biliary injuries. This permitted positioning a nasobiliary drain to reduce
      intrabiliary pressure and to bypass a lesion of the common hepatic duct. This
      nonoperative management allowed healing of fistulas within 20 days, without bile
      duct stricture (noted on the follow-up intravenous cholangiogram 18 months
      later).

PMID- 8749936
TI  - Mucosal proctectomy and colo-anal anastomosis as treatment of rectal atresia.
AB  - Rectal atresia is a rare condition in which the anus and sphincter muscles are
      normally developed. Therefore it seems logical to preserve those structures
      unaltered during surgical therapy. Mucosal proctectomy and colo-anal anastomosis
      is a safe, technically well known technique that achieves this goal.

PMID- 8749937
TI  - Esophageal duplication cyst associated with pulmonary cystic malformations.
AB  - Two cases of esophageal duplication cyst associated with pulmonary cystic
      malformations (cystic bronchiectasis with pneumonia in one, intrapulmonary
      bronchogenic cysts with bronchial atresia in the other) are reported. The
      coexistence of these complex anomalies supports the recognition that esophageal
      duplication cyst also is an entity of a broad spectrum of developmental
      abnormalities caused by abnormal budding of the primitive foregut. Nine cases of
      similar complex anomalies in the lung and esophagus have been reported. Although
      rare, this malformation complex should be borne in mind in the treatment of
      pediatric mediastinal and pulmonary malformations.

PMID- 8749938
TI  - Construction of female neourethra using a flipped anterior bladder wall tube.
AB  - Two cases in which a neourethra was constructed using a flipped anterior bladder
      wall tube are reported. One girl had lost her urethra secondary to a major
      urethrovaginal injury from blunt pelvic trauma, an in the other, the urethra had
      sloughed after cloacal reconstruction. Both patients had a closed bladder
      neck/proximal urethra and were received with a suprapubic cystostomy. A
      neourethra was constructed from an anterior bladder wall flap based distally. The
      flap was tubularized and flipped caudally to the site of the original external
      urethral meatus. Both girls are continent--one voids normally and the other is
      managed by clean intermittent catheterization. The flipped anterior bladder wall
      tube technique for construction of a female neourethra is suitable in patients
      with an absent urethra, particularly when the bladder neck/proximal urethra is
      closed.

PMID- 8749939
TI  - Urinary obstruction caused by factitious urethral stones: an amazing
      manifestation of Munchausen syndrome by proxy.
AB  - The diagnosis of Munchausen syndrome by proxy is frequently difficult to document
      and often delayed. A unique presentation of a case of Munchausen syndrome by
      proxy involving insertion of factitious stones in the lower urinary tract is
      reported.

PMID- 8749940
TI  - 3-Year-old phenotypic female with campomelic dysplasia and bilateral
      gonadoblastoma.
AB  - The authors report the case of bilateral gonadoblastomas in a phenotypic female,
      with a 46,XY karyotype, with campomelic dysplasia. Although campomelic dysplasia
      with gonadal dysgenesis should be expected to contribute to an increased risk of
      gonadoblastoma, this is the first documented case report of campomelic dysplasia
      and gonadoblastoma. Phenotypic females with campomelic dysplasia should be
      karyotyped once the skeletal dysplasia is recognized. phenotypic females with
      campomelic dysplasia should undergo gonadectomy if their karyotype includes a Y
      chromosome or fragment.

PMID- 8749941
TI  - Female hypospadias: a case report.
AB  - A case of proximal female hypospadias with urethral atresia is reported, and a
      nosological definition of this rare congenital anomaly is proposed. An attempt to
      clarify the difference between a urogenital sinus and a proximal or distal female
      hypospadias is made by examining the embryology of the urogenital tract.

PMID- 8749942
TI  - Complete disruption of the main pancreatic duct: a case successfully managed by
      percutaneous drainage.
AB  - The authors report on a 7-year-old boy who sustained blunt abdominal trauma on a
      bicycle handlebar. A large traumatic pancreatic pseudocyst developed, for which
      percutaneous external drainage under ultrasound guidance was performed. Both the
      catheter fistulogram and endoscopic retrograde cholangiopancreatogram showed
      complete disruption of the main pancreatic duct. During continuous external
      drainage, the pseudocyst disappeared. The drainage flow decreased gradually and
      ceased. The patient is well, with normal endocrine and exocrine pancreatic
      functions, 2 years after discharge.

PMID- 8749943
TI  - Familial multiple mesothelial cysts of the spleen.
AB  - A 5-month-old boy who was diagnosed as having hydrops fetalis at 25 weeks'
      gestation had severe ascites of unknown origin. At the age 12 months,
      ultrasonography and computed tomography showed multiple cysts in the spleen that
      were increasing in size rapidly. Splenectomy resulted in complete disappearance
      of the ascites. These cysts were diagnosed as mesothelial cysts because the cell
      lining of the splenic cysts stained positively with alcian blue and cytokeratin.
      The boy's mother had undergone splenectomy for splenic and retroperitoneal
      lymphangiomas at 4 years of age. Histological reevaluation showed that the lining
      of her splenic cysts had the same mesothelial components as her son's. Their
      chromosomal assay showed normal karyotypes. Mesothelial cyst of the spleen
      appears similar to splenic lymphangioma morphologically; however, bleomycin and
      OK-432 were not effective. Familial splenic mesothelial (epidermoid) cysts have
      been reported in three sets of siblings, but this is the first report of their
      occurrence in mother and son.

PMID- 8749944
TI  - Factor XI deficiency in an Ashkenazi Jewish child, causing severe postoperative
      hemorrhage.
AB  - Although inherited coagulation factor deficiencies with negative bleeding
      histories are rare, cases such as the one presented herein may not be diagnosed
      at the time of surgery and may experience severe hemostatic problems
      postoperatively. It may be prudent to obtain an activated partial thromboplastin
      time preoperatively for all Ashkenazi Jews, including those with a negative
      history for a hemostatic disorder, because of the high incidence of factor XI
      deficiency in their population. Surgeons and anesthesiologists should be aware of
      the existence of this and other uncommon hemostatic disorders and their treatment
      when faced with serious, apparently unexplained postoperative hemorrhage.

PMID- 8749945
TI  - Altered glycoprotein sugar-chain structures as possible diagnostic and prognostic
      markers in malignant tumors.

PMID- 8749946
TI  - Cytotoxicity of gallium nitrate in vitro using bladder cancer cells.
AB  - BACKGROUND: Gallium nitrate has been used systemically for some malignancies in
      clinical trials. Because bladder cancer has many transferrin (Tf) receptors and
      gallium has been reported to bind avidly with Tf receptors, gallium cytotoxicity
      and the possibility of intravesical instillation therapy with gallium nitrate
      were studied in vitro. METHODS: The bladder cancer cell lines J82, 639V, VMCuB1,
      SCaBER, and 5637 were used. The amount of Tf receptor was checked by a rosette
      assay. As a cytotoxicity assay, two experimental models were tested using two or
      72 hours of exposure to gallium solution. A gallium release study using 67Ga was
      done to investigate the movement of incorporated gallium. RESULTS: J82 had the
      most and SCaBER had the least Tf receptors. For 72 hours of exposure at gallium
      concentrations above 250 mumol/L, the inhibitory effect was a function of gallium
      concentration, and 100% cytotoxicity occurred at 2 mmol/L. At lower
      concentrations of gallium, the effect was related to the amount of Tf and the
      level of Tf receptor expression of the cells. With two hours of exposure, which
      was assumed to be a model of intravesical therapy, the inhibitory effect
      increased in proportion to gallium concentration and the frequency of treatment.
      Twenty mmol/L gallium effectively inhibited the growth in two hours of exposure.
      CONCLUSIONS: Intravesically administered gallium might be an effective therapy
      for bladder cancer, because its cytotoxicity is determined not by the amount of
      Tf receptor but by the gallium concentration and the duration of gallium
      exposure.

PMID- 8749947
TI  - Expression of CD44 splice variants in bladder cancer.
AB  - BACKGROUND: Recently, it was noted that CD44 participates in a wide variety of
      cell-cell or cell-matrix interactions including tumor metastasis and the altered
      expression of CD44 splice variants is helpful in the diagnosis of colon and
      breast cancer. The purpose of the study was to investigate altered expression of
      CD44 in bladder cancer. METHODS: Thirty-three surgical specimens of 22 patients
      and seven bladder cancer cell-lines were analyzed by various methods including RT
      PCR-Southern blotting. Northern blotting, and flow-cytometric analysis. RESULTS:
      In RT-PCR analysis, the hematopoietic variant and numerous additional variants
      were detected in all cell-lines and almost all surgical specimens. In three out
      of seven cell-lines of bladder cancer (42.9%), especially numerous larger bands
      (ladder pattern) were detected using RT-PCR. These three cell-lines expressed a
      smaller quantity of CD44 mRNAs and CD44 molecules than the other four cell-lines.
      In eighteen out of 22 (81.8%) bladder cancer specimens, we detected larger
      variants that exceed 1500 base pairs, compared with the detection in four out of
      eleven (36.4%) visually normal mucosa specimens (P < 0.05). However, there was no
      correlation between the expression of the larger variants and clinicopathological
      features. CONCLUSION: The quantitative and qualitative change of CD44 variants
      were demonstrated in bladder cancer.

PMID- 8749948
TI  - Immunohistochemical analysis of p53 and proliferating cell nuclear antigen (PCNA)
      in bladder cancer: positive immunostaining and radiosensitivity.
AB  - BACKGROUND: Preoperative radiation therapy followed by radical cystectomy for
      invasive bladder cancer has been considered beneficial for selected patients
      whose tumors display a pronounced initial response to radiotherapy. METHODS: In
      order to determine whether overexpression of p53 gene products or proliferating
      cell nuclear antigen (PCNA) can be used to predict the response of invasive
      bladder cancer to radiotherapy, an immunohistochemical study of bladder cancers
      with monoclonal antibodies to p53 or PCNA (PAb 1801 or PC10) was performed. The
      results of immunostaining of pretreatment biopsy specimens from 60 invasive
      bladder cancers were analyzed to determine the relationship between labeling for
      p53 or PCNA and radiosensitivity as determined by histopathological examination
      of cystectomy specimens obtained after preoperative radiation. RESULTS: The group
      with a good response to preoperative radiation therapy had better progression
      free rates than did the group with a poor response (P < 0.05). There was no
      significant difference in radiosensitivity between patients with primary tumors
      with negative and positive immunostaining for p53. On the other hand, the PCNA
      labeling index (LI) differed significantly between tumors with poor and good
      histopathological responses to radiation therapy (P < 0.05). CONCLUSION: No
      correlation was found between immunohistochemically detectable alterations of p53
      gene products and the radiosensitivity of invasive transitional cell carcinoma of
      the bladder. However, PCNA immunostaining may be useful for identifying patients
      for whom preoperative radiation might prove beneficial.

PMID- 8749949
TI  - Comparison of multidrug resistance gene expression levels with malignant
      potentials and influence of chemotherapy in urothelial cancers.
AB  - BACKGROUND: We sought to determine how often P-glycoprotein is involved in the
      drug-resistance of urothelial cancer, and whether MDR1 gene expression is
      correlated with tumor grade, invasiveness, or metastasis. METHODS: Forty-two
      tumor specimens and two normal bladder mucosal samples obtained from 34
      urothelial cancer patients were analyzed. Reverse-transcription and polymerase
      chain reaction were conducted. MDR1 mRNA levels were determined by measuring the
      relative ratio of the MDR1 to beta-2-microglobulin (b2 m) mRNA specific PCR
      products. RESULTS: The MDR1/b2 m in two normal urothelial samples were 0.044 and
      0.045. For untreated primary tumors, levels of MDR1 gene expression in 46% tumor
      samples were less than that of normal urothelium, while 27% showed expression
      levels with a MDR1/b2 m ratio more than 0.1. There was no statistical correlation
      between MDR1 mRNA level and tumor grade, stage, or metastatic status. There was
      higher MDR1 gene expression in two lymph node metastasis specimens and almost
      equal expressions in two more. There was no significant difference in the mean
      MDR1/b2 m ratio between postchemotherapy and untreated tumors. A remarkable
      elevation of the MDR1 mRNA level (15 times greater than prechemotherapy) was
      found in one tumor; mRNA levels of the multidrug resistance-associated protein
      (MRP) gene, glutathione S-transferase pi (GST-pi) gene or DNA topoisomerase II
      (topo II) gene did not increase. CONCLUSIONS: It is still unclear whether the
      MDR1 gene expression in urothelial tumor cells is inducible by the current
      combination chemotherapy regimens. RT-PCR quantitation is useful for determining
      the expression level of MDR1 gene in urothelial cancer.

PMID- 8749950
TI  - Shorter interval between cycles of cyclophosphamide, doxorubicin, cisplatin using
      recombinant human granulocyte colony-stimulating factor for urothelial cancer-
      phase I/II study.
AB  - BACKGROUND: Despite improvement in the response rate and protraction of the
      progression-free period of urothelial cancer produced by chemotherapy, severe
      bone marrow suppression often results in delays in the initiation of treatment
      cycles and/or decreases in drug dosages. Reduction of leukopenia during
      chemotherapy has been demonstrated by the combined administration of granulocyte
      colony-stimulating factor (G-CSF) in various malignancies. METHODS: A phase I/II
      study was conducted to assess whether the interval between cycles of CISCA
      (cyclophosphamide, doxorubicin, cisplatin) chemotherapy could be shortened under
      support of recombinant human granulocyte colony-stimulating factor (rhG-CSF) for
      urothelial cancer. Three or more patients with transitional cell carcinoma of the
      urinary tract were allocated to each of four different treatment intervals (step
      1: 28 days, step 2: 21 days, step 3: 17 days, and step 4: 14 days) by reducing
      the interval in a step-wise manner. Two mg/kg/day of a rhG-CSF, lenograstim, was
      injected subcutaneously on days 3 to 16 (until day 14 for the 14-day interval
      group). RESULTS: Sixteen patients were enrolled, four patients were treated with
      the step 1 protocol, five with step 2, four with step 3, and three with step 4.
      Leukopenia/neutropenia was the most severe toxic reaction, but none of the
      patients at any step manifested neutropenia of WHO grade 4 for more than four
      days. There were no significant differences in the hematological and
      nonhematological toxicities among the 4 steps. Seven of eight patients with
      measurable diseases were treated with CISCA on shortened schedules (steps 2-4),
      and one complete remission (CR) and four partial responses (PR) were
      demonstrated. CONCLUSIONS: CISCA chemotherapy supported by rhG-CSF was safely
      shortened to a 14-day interval in the pilot study. The potential role of rhG-CSF
      in shortening the interval of CISCA, as well as the benefit of the intensified
      schedule, remains to be clarified.

PMID- 8749951
TI  - Maximum flow rate--the single uroflowmetric parameter in clinical trials for
      benign prostatic hyperplasia?
AB  - BACKGROUND: Uroflowmetry parameters should be examined for both reliability and
      optimal test conditions in patients with benign prostatic hyperplasia (BPH),
      since the difference between one pre- and one post-intervention uroflow rate is
      usually evaluated in clinical trials of BPH. PATIENTS AND METHODS:
      Reproducibility of maximum flow rate (Qmax) or its modified forms, and the
      effects of urinary volume on the reproducibility were examined in terms of
      Spearman's correlation coefficient (r) in 67 BPH patients. RESULTS: Qmax had a
      higher r (0.672) as compared to other uroflow rates, such as mathematically
      modified forms of Qmax and adjusted values of Qmax on nomograms. Reliability was
      improved by bladder instillation (r = 0.811) or when voided volume was > or = 150
      ml or the ratio of volumes was < 2.0 (r = 0.690-0.736). CONCLUSION(S): Qmax,
      preferably performed with urinary volumes of more than 150 ml or the ratio of
      volumes less than 2.0, is the most practical single parameter at present in the
      comparison of two uroflowmetric tests in BPH treatment.

PMID- 8749952
TI  - Electroejaculation in patients with spinal cord injury: first report of a large
      scale experience from Japan.
AB  - BACKGROUND: Ejaculatory dysfunction is a substantial obstacle for spinal cord
      injured men who have a desire to father their own children. Electroejaculation
      can potentially solve this problem. Recently, Halsted et al. reported outstanding
      results of the rectal probe electrostimulation (RPE) using newly developed
      equipment (Seager Model). In this paper, we report the first large-scale clinical
      trial in Japan of RPE for spinal cord-injured men. METHODS: RPE using the Seager
      Model was attempted on 328 occasions in 53 patients with an age range of 19-47
      years; 1-38 years had elapsed since injury. RESULTS: Antegrade ejaculation was
      obtained in 46 patients (86.8%). Ninety-three percent of patients with upper
      motor neuron lesion-type neurogenic bladder produced antegrade ejaculation by
      RPE, whereas the rate in patients with lower motor neuron lesion type one was
      63.6% (P < 0.05). Semen analyses revealed affected sperm motility rate as low as
      17.2%. Artificial insemination from these husbands (AIH) was attempted on 54
      occasions in 11 wives of the patients. On April 2, 1992, we had the first
      recorded birth in Japan with the assistance of RPE and AIH. On July 21, 1993, we
      had another successful birth. CONCLUSIONS: These promising results will encourage
      Japanese researchers to use electro-ejaculation, although the low success rate in
      patients with lower motor neuron lesion-type neurogenic bladder and the low
      motility of the sperm are obstacles to be overcome.

PMID- 8749953
TI  - Bilateral peripelvic fat simulating renal pelvic tumor.
AB  - Lipomas are benign tumors which may simulate peripelvic masses and usually
      originate in the renal cortex or the perirenal adipose tissue. Excessive
      proliferation of the peripelvic fat of the kidney simulating a renal pelvic tumor
      was detected in our case, illustrating a rare instance in which the kidney was
      salvaged.

PMID- 8749954
TI  - Angiomyolipoma of the kidney with extension into the inferior vena cava.
AB  - Renal angiomyolipoma is a benign, nonaggressive hamartoma which rarely invades
      the vascular system. A case of angiomyolipoma of the right kidney with extension
      into the inferior vena cava, detected by ultrasonography, computed tomography (CT
      scanning), and magnetic resonance imaging (MRI) is presented. This tumor was
      found incidentally in a 31-year-old female who underwent CT scanning for
      unrelated abdominal problems. To our knowledge, only eight cases of
      angiomyolipoma with caval involvement have been reported in the world medical
      literature.

PMID- 8749955
TI  - Renal oncocytoma mimicking hemorrhagic renal cyst.
AB  - A case of oncocytoma, the radiological findings of which resembled a hemorrhagic
      renal cyst, is reported. Cyst fluid analysis demonstrated extremely high levels
      of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9).
      Preoperatively the lesion was regarded a malignant cyst, and radical nephrectomy
      was performed. Pathological diagnosis was renal oncocytoma with cystic
      degeneration. Although cystic change occasionally has been mentioned in
      oncocytoma, a high level of CEA and CA 19-9 in the cyst fluid of the cystic
      oncocytoma have not been reported. We discuss the variant forms of oncocytoma and
      tumor markers in the cyst fluid.

PMID- 8749956
TI  - In situ non-ischemic enucleation of multilocular cystic renal cell carcinoma
      using a microwave coagulator.
AB  - A case of multilocular cystic renal cell carcinoma is reported, in which nephron
      sparing surgery was done using microwave tissue coagulation. A 37-year-old man
      was referred to our outpatient clinic for a multilocular cystic tumor, 4.5 cm in
      diameter, in the middle-lower portion of the right kidney, which was detected by
      ultrasound during a health checkup. The patient had been found to have the same
      cystic mass on a CT done during another health checkup 1.5 years before. The
      tumor showed no growth during the 1.5-year period. With a diagnosis of
      multilocular cystic renal cell carcinoma, T2N0M0, in situ non-ischemic tumor
      enucleation was done using a microwave tissue coagulator (Microtaze, Heiwa
      Electronics Industry Inc., Tokyo). Operation time was 150 minutes and blood loss
      was 135 cc. The histological diagnosis was renal cell carcinoma, T2N0M0V0, cystic
      type, clear cell subtype, grade 1. Diagnostic imaging done postoperatively showed
      no sign of damage to renal function. In this report, the characteristics of
      multilocular cystic renal carcinoma are reviewed from the literature, and the
      advantages of nephron-sparing surgery for this type of renal tumor are discussed.
      In addition, an operative technique of tumor enucleation used in this case and
      the characteristics of Microtaze are introduced.

PMID- 8749957
TI  - Urachal adenocarcinoma accompanied by a large spherical calcified mass.
AB  - We report a case of urachal adenocarcinoma, accompanied by a large spherical
      calcified mass adherent to the bladder dome of a 63-year-old man. The patient
      underwent partial cystectomy including en bloc resection of the urachus, and
      remains free from the disease after a 32-month follow-up period.

PMID- 8749958
TI  - Bladder squamous cell carcinoma with human papilloma virus type 6 [HPV 6].
AB  - A 91-year-old male was diagnosed with squamous cell carcinoma of the urinary
      bladder. Molecular biological examination using the polymerase chain reaction
      (PCR) method demonstrated the presence of HPV type 6. HPV type 6 is considered
      very rare in urinary bladder malignancies.

PMID- 8749959
TI  - Pediatric triage.

PMID- 8749960
TI  - Minor head trauma, revisited.

PMID- 8749961
TI  - Multicenter study of creatine kinase-MB use: effect on chest pain clinical
      decision making.
AB  - OBJECTIVE: To determine whether creatine kinase-MB isomer (CK-MB) levels affect
      initial physician decisions regarding patients with potential cardiac chest pain.
      METHODS: A prospective, multicenter, observational cohort study was performed at
      seven university teaching hospital EDs. Hemodynamically stable chest pain
      patients > or = 25 years old and without ST-segment elevation on their ECGs were
      observed with one to two sets of CK-MB level determinations obtained three hours
      apart prior to disposition. The physicians committed to a dichotomous (yes/no)
      absolute decision regarding the diagnosis of myocardial infarction (MI), need for
      hospital admission, and need for coronary care unit (CCU) admission both before
      and after enzyme results were obtained. The physicians ranked the perceived
      importance of initial history and physical, serial clinical observation, initial
      ECG, and CK-MB level to their decision making (rank score: 1 = most important, 4
      = least important). RESULTS: Of the 1,042 patients enrolled, 777 (74.6%) were
      admitted to the hospital. For the 67 MI patients (8.6% of the admissions),
      changes in absolute decisions about the diagnosis of MI and planned CCU admission
      were associated with increased CK-MB importance (p = 0.04 and p = 0.02,
      respectively). Of the 146 patients who had new-onset angina or unstable angina,
      changes in absolute decisions were not associated with CK-MB importance. No
      patient who had MI or unstable angina was released from the ED. There were three
      of 67 (4%) MI patients and one of 146 (1%) unstable/new-onset angina patients
      initially slated for release home who were admitted to the hospital. CONCLUSIONS:
      For a minority of the patients who had subsequently proven MI, the CK-MB result
      helped guide disposition decisions. The CK-MB availability did not adversely
      impact the disposition of the patients who had unstable or new-onset angina.

PMID- 8749962
TI  - Sensitivity of new-generation computed tomography in subarachnoid hemorrhage.
AB  - OBJECTIVE: To determine the sensitivity of the initial new-generation CT (NGCT)
      scan interpretation for detection of acute nontraumatic subarachnoid hemorrhage
      (SAH) and to decide whether lumbar puncture (LP) should follow a "normal" NGCT
      scan. METHODS: A retrospective chart review was performed of patients admitted
      between March 1988 and July 1994 with proven SAH. Exclusion criteria were age < 2
      years, diagnosis other than acute SAH, history of head trauma within 24 hours
      before symptom onset, NGCT scan not done before diagnosis, and records not
      available. Patients were placed into two groups: symptom duration < 24 hours
      (group 1) and > 24 hours (group 2) prior to CT scan. The resolution of each NGCT
      scanner was recorded. An NGCT scanner was defined as a third-generation scanner
      or more recent. RESULTS: Of 349 SAH patients, 181 met inclusion criteria. The
      sensitivity of NGCT scans for SAH was 93.1% for the group 1 patients (n = 144)
      and 83.8% for the group 2 patients (n = 37). The overall sensitivity was 91.2%.
      All the patients who had SAH not detected by NGCT scans were diagnosed by LP.
      There was no significant relationship between NGCT scanner resolution and
      sensitivity for SAH. CONCLUSION: Initial interpretation of NGCT scans to detect
      SAH does not approach 100% sensitivity. A "normal" NGCT scan does not reliably
      exclude the need for LP in patients who have symptoms suggestive of SAH.

PMID- 8749963
TI  - Cognitive deficits in presumed minor head-injured patients.
AB  - OBJECTIVE: To determine the frequency of cognitive deficits in ED patients with
      presumed minor head injury and to identify factors in the initial history and
      physical examination predictive of cognitive deficits in these patients. METHODS:
      A prospective clinical study was performed over a nine-month period at a large
      community-based ED (60,000 patient annual census). Consecutive patients between
      16 and 50 years of age who presented to the ED with a history of blunt trauma or
      a deceleration injury to the head and a Glasgow Coma Scale (GCS) score of 14 or
      15 were included. Patients who were admitted to the hospital or who had an
      abnormal imaging study of the skull or brain also were excluded. Detailed history
      and physical examination findings were collected using a standardized data form.
      Cognitive testing was done at one week postinjury (Halstead-Reitan
      Neuropsychological Test Battery). RESULTS: Seventy patients were originally
      entered into the study, and 36 completed the follow-up. Those completing the
      study were more commonly employed and less likely to have used sensorium-altering
      drugs or ethanol. Of the 36 patients who completed the study, 42% had either mild
      or moderate cognitive deficits at one week postinjury. Abnormal cerebellar
      function during the initial visit was associated with the presence of cognitive
      deficits at follow-up (p = 0.004). However, only four of 15 (27%; 95% CI 8-55%)
      patients with a cognitive deficit had an abnormal cerebellar finding. CONCLUSION:
      Many patients with minor head injuries have cognitive deficits one week after
      injury. History and physical examination features are poor predictors of these
      deficits. Further studies are needed to evaluate the duration and final outcome
      of these cognitive deficits.

PMID- 8749964
TI  - Prospective assessment of presenting serum markers for cardiac risk
      stratification.
AB  - OBJECTIVE: To quantify the association of initial ED serum cardiac markers with
      the risk for life-threatening events (LEs) or need for lifesaving interventions
      (LIs) or administration of IV nitroglycerin. METHODS: A prospective,
      observational study was performed using a cohort of hemodynamically stable,
      hospitalized patients (age > or = 25 years) presenting with nontraumatic chest
      discomfort. Patients with ST-segment elevation on their initial ECGs were
      excluded. Presenting serum samples were assayed for serum myoglobin and creatine
      kinase-MB isomer (CK-MB) using the Opus and Stratus systems. Target cases were
      defined as patients having LEs (e.g., cardiogenic shock, ventricular
      fibrillation, cardiac arrest), requiring LIs (e.g., intubation, cardioversion,
      pacing, reperfusion therapy), or needing IV nitroglycerin within 48 hours.
      Manufacturer's thresholds defined abnormal marker levels. Abnormal ECGs were
      defined using the Brush criteria. RESULTS: Of the 178 eligible patients, 44 (25%)
      were target cases. Most (55%) target cases had blood drawn for assays within four
      hours of chest discomfort onset. The relative risk and sensitivity of the serum
      markers and the ECG for target cases follow: [table: see text] Of the seven
      patients with an LE/LI, six had blood drawn four hours or less after symptom
      onset; two LE/LI patients had abnormal myoglobin levels--no LE/LI patient had an
      abnormal CK-MB level. CONCLUSIONS: Isolated serum myoglobin and CK-MB levels
      obtained at patient ED presentation were not strongly associated with the 48-hour
      risk for LEs, LIs, or the use of IV nitroglycerin. Future studies of risk
      stratification should address the merits of serial serum marker measurements that
      extend up to 12 hours beyond patient symptom onset.

PMID- 8749965
TI  - Oral intubation using a lighted stylet vs direct laryngoscopy in older children
      with cervical immobilization.
AB  - OBJECTIVE: To compare the tracheal intubation success rates of blind oral
      intubation using a lighted stylet vs standard of direct laryngoscopy in
      anesthetized pediatric patients wearing rigid cervical collars. METHODS: Seventy
      eight children were randomly assigned to method of intubation (lighted stylet or
      direct laryngoscopy) and intubator; five patients were excluded after
      randomization. After sedation and paralysis, the patients were placed in rigid
      cervical spine collars to simulate intubating conditions for trauma patients.
      Three attempts at intubation were allowed. An observer recorded the following
      parameters during the procedure: 1) number of intubation attempts, 2) duration of
      each intubation attempt, and 3) complications. The intubators had limited prior
      experience with the lighted stylet technique. RESULTS: Thirty-three patients were
      in the lighted stylet group and 40 were in the laryngoscopy group. The patients
      in the lighted stylet group required more attempts prior to successful intubation
      (2.2 vs 1.5, p < 0.01), and the success rate was higher for the laryngoscopy
      group (26/33 vs 39/40, p < 0.05). CONCLUSIONS: Blind oral intubation using a
      lighted stylet under controlled conditions took longer than direct laryngoscopy.
      However, among those successful on the first intubation attempt, the times to
      intubation were not significantly different between groups (44.5 vs 52.9 sec).
      The lighted stylet technique is a viable alternative technique for intubating
      children who have concurrent cervical spine immobilization.

PMID- 8749966
TI  - Out-of-hospital rapid-sequence induction for intubation of the pediatric patient.
AB  - OBJECTIVE: To determine the effectiveness and morbidity of out-of-hospital rapid
      sequence induction (RSI) for endotracheal intubation (ETI) in the pediatric
      population. METHODS: The medical records were retrospectively reviewed for a
      consecutive series of pediatric patients undergoing out-of-hospital RSI by flight
      paramedics from July 1990 through July 1994. Patient demographics, pharmacologic
      agents, ED arterial blood gas data, pulmonary complications, and RSI-related
      complications were abstracted. RESULTS: Forty patients (31 injured, 9 medical)
      with a mean age of 8.1 years (range 0.5-17 years) underwent out-of-hospital RSI.
      Indications for intubation included hyperventilation (n = 20), combativeness (n =
      16), apnea (n = 5), and unknown (n = 5). Intubation mishaps occurred in 13
      patients (33%); these included multiple attempts (n = 9), aspiration (n = 8), and
      esophageal intubation (n = 1). The success rate of ETI was 97.5% (one failed
      attempt). Hemodynamic side effects occurred in three patients (8%); all three had
      bradycardia, with one developing hypotension. Bradycardia was associated with
      failure to pretreat with atropine (p < 0.05). Sixteen pulmonary complications,
      seven pneumonia (18%) and nine atelectasis (22.5%), occurred in 13 patients
      within the first ten hospital days. Intubation mishaps were not associated with
      pulmonary complications. There were six deaths, none associated with RSI.
      CONCLUSIONS: 1) Rapid-sequence induction is an effective method for obtaining
      airway control in the critically ill pediatric patient. 2) Intubation mishaps did
      not influence the rate of pulmonary complications. 3) Omission of atropine was
      associated with bradycardia during RSI in pediatric patients.

PMID- 8749967
TI  - Ethanol ingestion and related hypoglycemia in a pediatric and adolescent
      emergency department population.
AB  - OBJECTIVE: To estimate the frequency of associated hypoglycemia in an ethanol
      ingesting pediatric and adolescent population. METHODS: The study was a
      retrospective review of nondiabetic pediatric and adolescent patients with
      measurable ethanol levels (i.e., > or = 2 mmol/L) who had an ED serum glucose
      level determined. RESULTS: Over the four-and-a-half-year study period, there were
      254,234 pediatric visits. One hundred eleven had ethanol levels determined
      (0.044% of patients) due to suspected ingestion. Of these 111, 88 had glucose
      levels determined. The mean age of the 88 patients was 14 years, with a mean
      glucose level of 5.6 mmol/L [101 mg/dL; interquartile range (IQR) 4.7-6.3 mmol/L]
      and a mean ethanol level of 30 mmol/L (IQR 15-43 mmol/L). Glucose levels were <
      67 mg/dL (hypoglycemia) in three of the 88 (3.4%) ethanol-positive patients; all
      the hypoglycemic patients had significant behavioral changes. CONCLUSION: In this
      large retrospective series, the number of patients for whom the clinical
      suspicion of ethanol ingestion was confirmed was quite small. Hypoglycemia
      occurred in only 3.4% of these selected patients; all had altered behavior.
      Pediatric patients with presentations suggesting ethanol intoxication with
      altered behavior should be assessed for concurrent hypoglycemia.

PMID- 8749968
TI  - Advance directives in the emergency department: too few, too late.
AB  - OBJECTIVE: To determine: 1) the number of patients arriving at the ED who had
      executed an advance directive (AD), 2) how many of the patients who had an AD
      brought the AD with them, and 3) whether those patients who did not have an AD
      had ever discussed ADs with their primary care providers (PCPs) or had ever heard
      of an AD. METHODS: A cross-sectional, observational survey of a convenience
      sample of high-risk patients presenting to the ED of a university hospital was
      performed. Patients presenting to the ED for acute complaints who were elderly or
      had an underlying disease that suggested a risk of death in the near future were
      considered high risk. RESULTS: Of the 238 patients surveyed, 90% had PCPs.
      However, only 22% had ADs. Of these, only 23% brought the AD to the ED. Of the
      patients who did not have ADs, 95% had never discussed ADs with their PCPs, and
      42% did not know what an AD was. Blacks were less likely than whites to have ADs
      (p < 0.0002) or to know about them (p < 0.004). CONCLUSION: The majority of high
      risk patients presenting to this ED do not have ADs. Among those high-risk
      patients who did have ADs, fewer than 25% brought the ADs with them. The
      development of ADs for high-risk patients and the availability of ADs in the ED
      are woefully inadequate. Emergency physicians need to collaborate with PCPs to
      remedy these deficiencies.

PMID- 8749969
TI  - Emergency department do-not-attempt-resuscitation orders: next-of-kin response to
      the emergency physician.
AB  - OBJECTIVE: To evaluate the response by families of incompetent, chronically
      debilitated, and/or terminally ill patients who were contacted for do-not-attempt
      resuscitation (DNAR) status by an emergency physician (EP). METHODS: A
      prospective observational study was performed to assess next-of-kin willingness
      to support DNAR status for incompetent, chronically debilitated, and/or
      terminally ill patients. The families also were contacted by telephone follow-up
      48-72 hours after the ED visit. Upon follow-up evaluation, the families were
      surveyed regarding prior DNAR instructions and their perceptions of the
      establishment of DNAR status in the ED. The study was conducted in an urban
      teaching hospital with an emergency medicine residency training program. RESULTS:
      Of the 71 patient families contacted, 60 (85%) of the patients had DNAR orders
      written in the ED. The families of these 60 patients had no negative response
      regarding contact by ED personnel. Of the 11 (15%) patients whose families wished
      no DNAR order, only two families had negative responses to being contacted by the
      EP. In both cases the families had previously given detailed instructions to the
      chronic care facility. CONCLUSION: The EP can play an important role in assisting
      the decision making process of families of incompetent, chronically debilitated,
      and/or terminally ill patients regarding institution of DNAR orders in the ED.
      Improved communication regarding existing DNAR orders with chronic care
      facilities might minimize the rare complaints received from families with
      preestablished DNAR orders.

PMID- 8749970
TI  - Effects of parental presence during children's venipuncture.
AB  - OBJECTIVE: To determine whether parental presence during venipuncture (VP)
      altered self-reported distress of the child, the parent, or the health
      professional (HP) performing VP. METHODS: During nine consecutive months, 130
      nonconsecutive 8-18-year-old children having VP in an urban pediatric ED were
      prospectively randomized into two groups of 65 patients each. Before VP, every
      child, parent, and HP completed a questionnaire developed to measure
      epidemiologic variables believed to influence distress during VP. The patients
      were randomized to have either a parent present or both parents absent during VP.
      The patients, the parents, and the HPs privately self-reported their distress
      during VP on a visual analog scale (VAS). Statistical significance was determined
      by the Mann-Whitney U (rank-sum) test. RESULTS: In the parent-present group,
      distress scores were lower for the parent (p < 0.01) and for the child (p < 0.04)
      than they were in the parents-absent group. The HP performing VP had no
      difference in distress scores with and without parental presence (p < 0.55).
      CONCLUSIONS: Parents and children having VP have less distress with parental
      presence. Health professional distress is not affected by parental presence.

PMID- 8749971
TI  - Improved pediatric patient flow in a general emergency department by altering
      triage criteria.
AB  - OBJECTIVE: To evaluate the effect of altering pediatric triage criteria on ED
      triage scoring and patient flow. METHODS: A prospective observational study of a
      pediatric triage modification was performed. Data for all pediatric patients
      presenting to an urban general ED during a six-month study period were collected.
      After the first three months, pediatric triage criteria were altered by elevating
      the acuity of several historical items and specifically listing abnormal signs
      and symptoms. Outcome measures included triage score assignment, criteria making
      the patient emergent, proportion of emergent or urgent triage assignments, and
      times to examination, disposition, and admission. RESULTS: Altering pediatric
      triage criteria resulted in a significant (p < 0.05) increase in the number of
      patients triaged as emergent (2% vs 15%) or urgent (48% vs 55%). In addition, for
      emergent and urgent patients there was a significant decrease (p < 0.05) in the
      mean times to ED examination (50 vs 44 min), floor admission (355 vs 245 min),
      and intensive care unit admission (221 vs 132 min). The triage changes that had a
      significant impact on these results were a history of color change, decreased
      activity, and prematurity with complications. CONCLUSIONS: A significant
      improvement in pediatric patient flow occurred after posting age-specific
      abnormal signs and symptoms as well as elevating triage acuity for specific
      historical clues.

PMID- 8749972
TI  - Prospective evaluation of emergency medicine instruction for rotating first
      postgraduate-year residents.
AB  - OBJECTIVE: To determine whether either bedside teaching alone (group A) or
      bedside teaching with written course materials (group B) improved written
      examination scores, satisfaction with the rotation, or clinical grades of
      rotating PGY1 residents. METHODS: A prospective, controlled educational trial was
      conducted. Sixty-five PGY1 residents from diverse specialties rotated in the ED
      for one month over a ten-month study period, and were included in the study. The
      PGY1 residents were assigned to group by month of rotation. All the PGY1
      residents received unstructured bedside teaching by emergency medicine (EM)
      residents and faculty. In addition, group B received written course materials on
      day 1. RESULTS: Mean posttest scores were higher than mean pretest scores for the
      interns considered as a whole (p < 0.0001), but mean pretest, posttest, and
      clinical grades were comparable across instructional groups. Mean satisfaction
      ratings were higher for group A than for group B (p < 0.015). The interns
      specializing in EM achieved higher mean test scores (p < 0.013) and clinical
      grades (p < 0.003) than did the interns specializing in another medical
      specialty. CONCLUSION: Both instructional methods were associated with improved
      written test performance. Written course materials did not augment bedside
      teaching in terms of test scores, clinical grades, or satisfaction with the
      rotation. At a university-based, high-volume ED, bedside teaching offers
      educational benefit to rotating PGY1 residents that may not be augmented by
      written course materials.

PMID- 8749973
TI  - Pediatric vomiting.

PMID- 8749974
TI  - A new tool for teaching and supervising direct laryngoscopy.

PMID- 8749976
TI  - Transport of assaulted patients using nonmedical personnel.

PMID- 8749975
TI  - Blood ethanol estimation: a comparison of three methods.

PMID- 8749977
TI  - De-solv-it for hot paving asphalt burn: case report.

PMID- 8749978
TI  - Child sexual abuse training in emergency residency programs.

PMID- 8749979
TI  - Depression and suicide on Gotland. An intensive study of all suicides before and
      after a depression-training programme for general practitioners.
AB  - In 1983 and 1984, the Swedish Committee for the Prevention and Treatment of
      Depression (PTD) organised a postgraduate training programme on the diagnosis and
      treatment to all the general practitioners on Gotland, Sweden. In the following
      years, the frequency of suicide and inpatient care for depression decreased
      significantly, as well as the frequency of sick leave for depression. The results
      of the Gotland study have provided evidence for the view that early recognition
      and adequate treatment of depression is one essential method of suicide
      prevention (Rutz et al., 1989; Rutz et al., 1992). A detailed retrospective
      clinical analysis, of all 115 consecutive suicide victims on Gotland between 1981
      and 1992 presented in this study, showed that male gender and violent methods
      were overrepresented. 50 suicides had a DSM-III-R axis I diagnosis and half of
      them (n = 25) had primary major depression. Bipolar II disorder was relatively
      overrepresented in this sample. After the PTD programme, the proportion of
      depressive suicides was significantly lower than before. This finding strongly
      suggests that the significant decrease in the suicide rate after the PTD
      programme is a direct result of the robust decrease in depressive suicides of the
      area served by trained GPs. The practical importance of this finding is briefly
      discussed.

PMID- 8749980
TI  - International study of expert judgement on therapeutic use of benzodiazepines and
      other psychotherapeutic medications: II. Pharmacotherapy of anxiety disorders.
AB  - OBJECTIVE: To assemble expert clinical experience and judgement in the treatment
      of anxiety and related disorders in a systematic, quantitative manner. METHODS: A
      panel of internationally recognized Experts in treating anxiety and depression
      was constituted by multistage peer nomination. 90% completed a questionnaire.
      This report focuses on case vignettes of 7 anxiety disorders followed by
      questions about relevant therapeutic options. RESULTS: Panelists usually
      recommended both psychological and pharmacological interventions. Most favored
      antidepressants, usually tricyclic, for agoraphobia, panic and OCD; beta-blockers
      for specific social phobia; and benzodiazepines for GAD and adjustment disorder.
      Some Experts favored polypharmacy, usually an antidepressant and a
      benzodiazepine. The majority usually advocated pharmacotherapy for 6 months or
      more. They recommended the same duration of treatment with benzodiazepines and
      other medications, except for GAD. CONCLUSIONS: The responses of the Expert Panel
      imply that; (1) most anxiety disorders are serious and merit vigorous, prolonged
      pharmacotherapy; and (2) antidepressants and benzodiazepines are effective and
      safe for long-term treatment of these conditions. This outcome contrasts with the
      widespread apprehension about long-term pharmacotherapy, especially with
      benzodiazepines, and some regulatory views.

PMID- 8749981
TI  - Sustained facial muscle activity during REM sleep and its correlation with
      depression.
AB  - Recently, we proposed that the coupling of cognitive activation and diminished
      arousal during REM sleep may have a mood regulating effect. Conversely, increased
      arousal during REM sleep may be associated with mood dysregulation. In this
      paper, the desensitization model is described, and data are presented on the
      association between motor activity during REM sleep, wakefulness and severity of
      depression. Motor activity sleep EEG data and two measures of depressive severity
      (BDI and HRSD) were obtained from 23 depressed patients. BDI scores were
      significantly correlated with motor activity only during REM sleep. HRSD scores
      were correlated with motor activity only during quiet wakefulness. These findings
      are consistent with the theoretical perspective that dysregulation in arousal
      mechanisms during REM sleep may promote mood disturbance during the depressive
      episode.

PMID- 8749982
TI  - Personality disorders and personality variations in relatives of patients with
      bipolar affective disorders.
AB  - Family studies may elucidate etiological relationships between two
      psychopathological conditions. This study explored the prevalences of personality
      disorders (DSM-III-R) and the variation of personality traits measured by the
      Munich Personality Test (MPT) in first-degree relatives of patients with bipolar
      disorder in comparison to control families recruited in the general population.
      Although the overall prevalence of having any personality disorder did not
      distinguish both groups of relatives we found significantly more compulsive
      personality disorders among relatives of probands with bipolar disorder.
      Relatives of patients with bipolar disorder also revealed significantly higher
      mean scores of "rigidity' (MPT); other personality traits, including neuroticism
      and extraversion, did not distinguish both groups. The observed differences in
      personality features between both groups of relatives are not mediated by current
      or previous axis I disorders. Therefore, they may reflect overlap of etiological
      factors of familial origin.

PMID- 8749983
TI  - The reliability and validity of a structured interview for the assessment of
      infectious illness symptoms.
AB  - Respiratory infections are the leading cause of morbidity in community
      populations. We developed a structured interview based on the Health Review (Rose
      et al., Psychosom. Med. 40: 142-165, 1978) to provide a simple method for
      periodic assessment of infectious illness, particularly upper respiratory
      infections. Congruence between interview data and physician diagnoses
      demonstrated excellent agreement regarding the presence or absence of an
      infection. Subjects who showed a clinically significant increase in antibody
      titers to an influenza virus vaccine reported fewer than half as many respiratory
      infections in the subsequent year as subjects who did not show a significant
      response. Interrater and test-retest reliabilities were satisfactory. These data
      support the reliability and validity of this method of assessing infectious
      illnesses.

PMID- 8749984
TI  - Assessing chronic illness representations: the Implicit Models of Illness
      Questionnaire.
AB  - Data were collected from three samples using the Implicit Models of Illness
      Questionnaire (IMIQ) to assess illness representations as described in the self
      regulation model of common sense illness representations. A factor structure was
      identified which displayed some similarities to the common sense model. This
      structure was used to examine illness representations of students and patients
      concerning three illnesses-rheumatoid arthritis (RA), multiple sclerosis (MS),
      and human immunodeficiency virus (HIV). Representations differed across illnesses
      and respondent status (patient vs. student). Students rated individuals as having
      more personal responsibility for RA or MS than did patients; moreover, the
      difference between patient/student ratings was greater with respect to MS than it
      was for RA. Patients were more aware of the variable nature of RA and MS symptoms
      than were students. This study demonstrates the value of the IMIQ as a tool for
      assessing illness cognitions and suggests that illness representations differ as
      a function of personal experience and personal relevance.

PMID- 8749985
TI  - Does sexual coercion play a role in the high-risk sexual behavior of adolescent
      and young adult women?
AB  - Sexual coercion and its relationship to high-risk sexual behavior were examined
      in five samples of young women. Sample 1 (N = 22) consisted of sexually active
      adolescents aged 15 to 19. Samples 2 (N = 206) and 3 (N = 70) were recruited from
      among patients at three sexually transmitted disease clinics. Sample 4 (N = 51)
      consisted of young homeless women living on the street in a large city. Sample 5
      (N = 51) was recruited from among young women on a college campus. Across all
      samples, 44.4% of women indicated that they had been forced into some form of
      sexual activity against their will. Self-reports of sexually coercive experiences
      were consistently related to risky sexual behavior. It appears that many young
      women are coerced into engaging in high-risk sexual behavior. This implies the
      need for greater attention to male coercive sexual behavior and women's skills
      for coping with such behavior.

PMID- 8749986
TI  - Aggressiveness, dominance, developmental factors, and serum cholesterol level in
      college males.
AB  - The present study was conducted to examine for college males relations between
      aggressiveness (or expressive hostility) and dominance and (a) particular
      developmental experiences and (b) total serum cholesterol. Aggressiveness but not
      dominance was found to be positively related to subjects' reports of their
      parents' behavior which reflected (a) less genuine acceptance, (b) more
      interference in the person's desires as a child, and (c) more punitiveness. For
      low-physically fit subjects, both aggressiveness and dominance were found to be
      positively related to levels of total serum cholesterol. These relations are
      congruent with the notion that both aggressiveness and dominance may contribute
      to hastening coronary atherosclerosis and risk of CHD via elevated levels of
      plasma lipids. It should be noted, however, that the relations obtained in the
      present study were all modest in size. For high-physically fit individuals
      associations were not found between total serum cholesterol and either
      aggressiveness or dominance. These results suggest that good physical fitness may
      attenuate the degree to which either aggressiveness or dominance may adversely
      affect health via elevated levels of cholesterol.

PMID- 8749987
TI  - Burnout, self- and supervisor-rated job performance, and absenteeism among
      nurses.
AB  - This study examined how job stress and work support predict the experience of
      burnout and how burnout is related to absenteeism and job performance in a sample
      of 73 registered nurses. The current study expanded on previous findings by
      including supervisor ratings of performance and employee records of absenteeism
      in addition to self-report measures. It also examined the extent to which burnout
      may mediate the relationships of job stress and social support with these
      performance indicators. Analyses indicated that levels of work support and job
      stress were both significant predictors of burnout. Additionally, higher burnout
      levels were significantly associated with poorer self-rated and supervisor-rated
      job performance, more sick leave, and more reported absences for mental health
      reasons. Finally, further analyses suggest that level of burnout served as a
      mediator of the relationships between social support and self-rated job
      performance, absences for mental health reasons, and intentions to quit. The
      findings suggest that burnout not only may negatively impact healthcare
      providers, but also may influence objective absenteeism and supervisor
      perceptions of employee performance.

PMID- 8749988
TI  - Hostility and erosion of marital quality during early marriage.
AB  - We examined the association between hostility and longitudinal changes in marital
      quality in a sample of 53 newlywed couples who were in their first marriages and
      were without children. Spouses' reports of marital quality were assessed
      initially at an average of 5 months into marriage and, thereafter, at three
      follow-up points approximately 1, 2, and 3 years subsequent to the date of
      marriage. Individual growth models were computed to assess the rate of change of
      marital quality. Hostility among husbands was significantly associated with
      linear decreases in their own, and their wives', reports of marital quality, even
      after controlling for the passage of time and the correlated variable of
      neuroticism. Results are consistent with the psychosocial vulnerability model of
      hostility and illness (Smith, Health Psychol. 11: 139-150, 1992), which posits
      that associations between hostility and heightened risk for morbidity and
      mortality are partially mediated by poor-quality relationships that develop as a
      consequence of the abrasive interpersonal properties of hostility.

PMID- 8749989
TI  - Involvement of respiratory muscles in adult-onset dystonia: a clinical and
      electrophysiological study.
AB  - Involvement of respiratory muscles is unusual in dystonia, but its occurrence may
      be underestimated either because it is not conspicuous or because it is
      improperly imputed to another cause. Three patients who had adult-onset dystonia
      and who were exhibiting respiratory problems were examined clinically and
      electrophysiologically. In the three patients the onset was focal-cervical in two
      and blepharospasm in one. The respiratory problems appeared later. The first
      patient had involuntary deep and loud inspirations combined with spasms of axial
      dystonia, the second complained of breathing arrests, and the third had deep
      inspirations mainly on speaking or reading aloud, thus causing broken speech.
      Electromyographic findings, including of the diaphragm, were quite consistent
      with a respiratory involvement in these three cases of dystonia. Assuming that
      respiratory troubles could be in the first sign of a focal dystonia,
      electrophysiological studies of respiratory muscles could be used to confirm
      this.

PMID- 8749990
TI  - Chronic acquired hepatocerebral degeneration: case reports and new insights.
AB  - Chronic acquired hepatocerebral degeneration (CAHD) is a heterogeneous disorder
      that can occur with a primary neurologic, hepatic, or combined presentation.
      Little has been added to the understanding of this disorder since the detailed,
      early clinical and pathological descriptions. The spectrum of clinical
      presentations can be neuropsychiatric (apathy, lethargy, excessive somnolence), a
      movement disorder (ataxia, tremor, chorea, parkinsonism, myoclonus, dystonia), or
      both. Cortical laminar necrosis and polymicrocavitation in the cortex and basal
      ganglia are combined with cerebral and cerebellar atrophy. Microscopically,
      Alzheimer type II astrocytes and cytoplasmic glycogen granules are
      characteristic. Recent neuroradiological observations in patients with liver
      failure have shown a specific magnetic resonance (MR) imaging appearance with a
      hyperintense T1 signal in the pallidum, putamen, and, rarely, mesencephalon.
      Using clues from a similar MR appearance in patients receiving total parenteral
      nutrition as well as animals given parenteral manganese, and the knowledge that
      manganese is cleared by the hepatobiliary system, deposition of manganese in the
      brain is postulated in patients with CAHD. In this review we describe three cases
      of CAHD with detailed clinical and radiological documentation and discuss the
      aforementioned pathogenetic mechanisms.

PMID- 8749991
TI  - The audiogenic startle response in Tourette's syndrome.
AB  - We report the results of a study in which we examined the auditory startle
      responses (ASR) of 8 patients with Tourette's syndrome and 15 normal controls,
      none of whom reported or manifested exaggerated startle responses clinically. The
      ASR in two patients failed to habituate with repetition, a finding not present in
      any of the controls. There was no correlation between the presence or absence of
      exaggerated ASRs and the severity of the patients' tics. This study demonstrates
      that some patients with Tourette's syndrome have exaggerated audiogenic startle
      responses that may be clinically asymptomatic.

PMID- 8749992
TI  - Chronic L-DOPA administration induces dyskinesias in the 1-methyl-4- phenyl
      1,2,3,6-tetrahydropyridine-treated common marmoset (Callithrix Jacchus).
AB  - Dyskinesias occur in the majority of patients with Parkinson's disease
      chronically treated with L-DOPA and also occur in several nonhuman primate
      species after 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) and L-DOPA
      treatment. The common marmoset (Callithrix jacchus) shows parkinsonian motor
      deficits after MPTP administration, and we now report dyskinesias occurring in
      this species during chronic L-DOPA exposure. Marmosets rendered chronically
      parkinsonian after MPTP administration were treated orally with L-DOPA plus
      carbidopa for 3 weeks. After several days the animals began to display chorea,
      choreoathetosis, and dystonia. The severity of dyskinesias varied between the
      animals, with the most severely parkinsonian animals displaying the most
      dyskinetic movements. Each animal showed an idiosyncratic pattern of dyskinesias,
      which was highly reproducible. These L-DOPA-primed animals also received other D2
      D1, and mixed D1/D2 agonist drugs. Quinpirole, bromocriptine, pergolide,
      apomorphine, and A-77636 all produce dyskinesias that were identical in character
      to those seen after L-DOPA administration, but the D1 agonist A-77636 gradually
      abolished dyskinesias while preserving its antiparkinsonian activity. The MPTP
      treated marmoset provides a useful model in which to study dyskinesias in
      Parkinson's disease and to examine new therapeutic strategies aimed at
      alleviating this common side effect of chronic dopamine replacement therapy.

PMID- 8749993
TI  - Modulation of electromyographic activity of wrist flexor and extensor muscles in
      patients with writer's cramp.
AB  - Patients with writer's cramp have two well-recognized neurophysiological
      abnormalities: reduced reciprocal inhibition of the wrist flexor motoneurons at
      rest, and increased cocontraction of antagonist muscles of the forearm during
      voluntary activity. In this article we present evidence for an impaired
      integration of sensory inputs into the voluntary motor activity during
      performance of a force-related task in patients with writer's cramp. Normal
      (control) subjects and patients activated wrist flexor and extensor muscles to
      maintain a predetermined level of force. Electrical stimuli were applied to
      median and radial nerve afferents and the modulatory effects induced in the
      electromyographic (EMG) activity were measured. For each muscle studied and nerve
      stimulated, we defined a characteristic sequence of excitatory (E) and inhibitory
      (I) phases of modulation of the averaged rectified EMG activity in control
      subjects. E and I phases were thought to represent excitation and inhibition,
      respectively, of the corresponding motoneuronal pool to homonymous or reciprocal
      afferent inputs. There were no differences between control subjects and patients
      regarding the level of background EMG activity in the agonist muscles during
      wrist flexion or wrist extension. In the agonist wrist flexors, patients had
      reduced homonymous and reciprocal inhibition. In the agonist wrist extensors,
      patients had reduced reciprocal excitation and reciprocal inhibition. These
      results are compatible with an abnormal CNS processing of the inputs generated by
      external stimuli during voluntary contraction of wrist flexor and extensor
      muscles. Defective integration of inputs from peripheral nerve afferents into the
      command for voluntary movement may partly underlie the pathophysiology of the
      motor dysfunction in patients with writer's cramp.

PMID- 8749994
TI  - Saccadic eye movements in hyperekplexia.
AB  - Hyperekplexia is an autosomal dominant disorder characterized by excessive
      startle responses followed by a temporary generalized stiffness. The startle
      response is generated in the medial bulbopontine reticular formation in the lower
      brainstem. The pulse generator of horizontal saccadic eye movements is localized
      in the pontine paramedian reticular formation. Measurements of horizontal
      visually evoked random saccades, antisaccades, and saccades toward remembered
      targets were performed in seven patients with familial hyperekplexia and seven
      health age-matched controls. The peak velocity of all three kinds of saccades was
      reduced (p < 0.0001) compared with that of controls. Latencies were marginally
      longer in the patient group (p = 0.0486). Saccadic gains did not differ between
      patients and controls. The ability to make antisaccades, saccades toward
      remembered targets, and the ability to suppress reflex saccades are similar in
      patients and controls. These data suggest that the origin of the excessive
      startle response is probably more due to a different modulation in the brainstem
      than to altered cortical influence.

PMID- 8749995
TI  - Parkinsonism and dilatation of the perivascular spaces (etat crible) of the
      striatum: a clinical, magnetic resonance imaging, and pathological study.
AB  - Two men, 89 and 83 years of age, presented with predominantly axial parkinsonian
      signs. In both cases, magnetic resonance imaging of the brain showed numerous
      small foci, delineating the striatum. The lesions had the same signal as cerebral
      spinal fluid in both T1 and T2 sequences. Postmortem examination of the brain
      showed numerous lacunes due to dilatation of the perivascular spaces, frequently
      associated with alterations of the surrounding brain parenchyma. Typical changes
      of Parkinson's disease were associated in one case. Such vascular changes may
      produce, or modify, a parkinsonian syndrome.

PMID- 8749996
TI  - Motor function in a patient with bilateral lesions of the globus pallidus.
AB  - This study describes the long-term deficits of a patient who, after a toxic
      encephalopathy, sustained extensive bilateral damage to both segments of the
      globus pallidus (GP) and the right substantia nigra (SN). There were no signs of
      lesions of the pyramidal tracts or of other motor structures. The most obvious
      deficits were an abnormal gait with an exaggerated knee extension and a tendency
      to fall slowly, especially when pushed backward. In contrast, Romberg's test on
      an unstable platform was normal, as were long-latency leg reflexes induced by
      perturbations. Inadequate anticipatory and compensatory postural responses, in
      particular across the hip and knee joints, and slow movements seemed responsible
      for the falls. Muscle tone was normal but reflex studies showed signs of abnormal
      facilitation and inhibition at various levels of the neuraxis. We conclude that
      the GP and SN lesions caused defective input to premotor cortical and brain stem
      target zones. Dysfunctioning of these zones leads to improper control of the
      descending ventromedial motor system responsible for locomotion, postural
      control, and reflex status. The deficits in upper extremity motor performance
      included delayed and slow movements, inaccurate amplitudes of ballistic
      responses, a lack of predictive control, and deficits in bimanual coordination.
      Sensory feedback, proprioceptive more than visual, played a powerful compensating
      role in rapid aiming movements. Regional blood flow (studied using 15(O)2) was
      reduced in multiple frontal cortical regions, among which are the hand areas of
      the supplementary and premotor cortex. We hypothesize that this reflected
      impaired functioning of these areas, caused by defective bilateral output from GP
      and SN, and resulting in the motor deficits of the arm and hand.

PMID- 8749997
TI  - Automobile driving in Huntington's disease.
AB  - We assessed the influence of the neurological and cognitive impairments of
      Huntington's disease (HD) on automobile driving. In a group of 73 HD outpatients,
      53 (72%) continued to drive after illness onset. Those no longer driving had more
      severe symptoms than those still driving. Twenty-nine HD patients who were still
      driving and 16 healthy control subjects underwent a clinical examination, a
      cognitive examination, a driving-simulator assessment, and completed
      questionnaires about driving history and habits. HD patients performed
      significantly worse than control subjects on the driving-simulator tasks and were
      more likely to have been involved in a collision in the preceding 2 years (58% of
      HD vs. 11% of control subjects). Patients with collisions were less functionally
      impaired but had slower simple reaction time scores than did those without
      collisions. HD patients are at increased risk for accidents, but patients who
      have accidents are not easily distinguished from those who do not.

PMID- 8749998
TI  - Associated movement as a sequel to thoracotomy: aberrant regeneration to the
      latissimus dorsi muscle.
AB  - We describe two patients with unusual associated movements as a sequel to
      thoracotomy. The two patients developed involuntary twitchings of the latissimus
      dorsi, which were induced by contractions of the adjacent muscles, the serratus
      anterior muscle in patient 1 and the external intercostal muscle in patient 2,
      after lobectomy for lung cancer. Electrophysiological and radiological studies
      showed that aberrant regeneration from the adjacent nerves to the denervated
      latissimus dorsi could be responsible for the associated movements.

PMID- 8749999
TI  - Tardive tourettism after exposure to neuroleptic therapy.
AB  - A case of neuroleptic-induced adult-onset tardive tourettism is presented with
      video documentation. After prolonged neuroleptic therapy, the patient developed
      motor and vocal tics at 36 years of age. The tics were identical to those seen in
      childhood-onset Tourette's syndrome. These cases are rare and have been
      considered by some to represent tardive akathisia. Previous reports of tourettism
      after neuroleptic therapy are reviewed.

PMID- 8750000
TI  - Blepharospasm and jaw closing dystonia after parietal infarcts.

PMID- 8750001
TI  - Zotepine in levodopa-induced Psychosis.

PMID- 8750002
TI  - Cervical dystonia as a probable consequence of focal cerebral lesion.

PMID- 8750003
TI  - Levodopa-induced convulsion: a case report.

PMID- 8750004
TI  - Bipolar affective disorder and unilateral parkinsonism after a brainstem
      infarction.

PMID- 8750005
TI  - Cervical dystonia and botulinum treatment: is electromyographic guidance
      necessary?

PMID- 8750006
TI  - Cerebral blood flow in corticobasal degeneration.

PMID- 8750007
TI  - Videotape quality.

PMID- 8750008
TI  - Gene therapy for the haemophilias.

PMID- 8750009
TI  - The choice of prodrugs for gene directed enzyme prodrug therapy of cancer.
AB  - Prodrugs are chemicals that are pharmacodynamically and toxicologically inert but
      which can be converted to highly active species. In cancer chemotherapy, enzyme
      activated prodrugs have been effective against certain animal tumours. However,
      in the clinic it has been found that human tumours containing appropriately high
      levels of the activating enzymes were rare and not associated with any particular
      type of tumour. Gene directed enzyme prodrug therapy (GDEPT) attempts to overcome
      this problem by killing tumour cells by the activation of a prodrug after the
      gene encoding for an activating enzyme has been targeted to the malignant cell.
      Here we summarise the various enzyme/prodrug systems that have been proposed for
      cancer therapy and comment on their suitability for GDEPT. This is because
      systems developed for other applications such as antibody directed enzyme prodrug
      therapy (ADEPT) may not be suitable for GDEPT. What is required are nontoxic
      prodrugs that can be converted intracellularly to highly cytotoxic metabolites
      that are not cell cycle specific in their mechanism of action. The active drugs
      released should also be readily diffusible and exert a bystander effect.
      Alkylating agents best meet these criteria. An example of a suitable
      enzyme/prodrug system may be a bacterial nitroreductase that can convert a
      relatively nontoxic monofunctional alkylating agent to a difunctional alkylating
      agent that is some ten thousand times more cytotoxic.

PMID- 8750010
TI  - Cationic liposome-mediated gene transfer.
AB  - Direct gene transfer for the treatment of human diseases requires a vector which
      can be administered efficiently, safely and repeatedly. Cationic liposomes
      represent one of the few examples that can meet these requirements. Currently,
      more than a dozen cationic liposome formulations have been reported. These
      liposomes bind and condense DNA spontaneously to form complexes with high
      affinity to cell membranes. Endocytosis of the complexes followed by disruption
      of the endosomal membrane appears to be the major mechanism of gene delivery. The
      effectiveness and safety of this DNA delivery method has been established in many
      studies. Based on these results, two human gene therapy clinical trials using
      cationic liposomes have been conducted and more trials will be started in the
      near future. The simplicity, efficiency and safety features have rendered the
      cationic liposome an attractive vehicle for human gene therapy.

PMID- 8750011
TI  - Retroviral end-point titer is not predictive of gene transfer efficiency:
      implications for vector production.
AB  - Efforts to improve gene transfer (transduction) efficiency achieved with
      retroviral vectors often focus on increasing the end-point titer. In this study,
      we assayed more than 70 retroviral vector supernatants for end-point titer and
      for the ability to transfer reporter genes into cell populations (referred to as
      transduction efficiency). We found no correlation between end-point titer and
      transduction efficiency. We also show that increasing end-point titer by
      ultrafiltration does not necessarily increase transduction efficiency. Evidence
      presented shows that nontransducing retroviral particles interfere with
      transducing virions and reduce transduction efficiency without reducing end-point
      titer. We have investigated production parameters and stability of retroviral
      vector particles using transduction efficiency as a measure of supernatant
      potency. Analysis of the production kinetics showed that the rate of virus
      production was marginally higher at 37 degrees C than at 32 degrees C. However,
      recombinant amphotropic retrovirus particles are significantly more stable at 32
      degrees C than at 37 degrees C. In addition, we show that short incubation
      periods are sufficient to yield supernatants with high transduction efficiencies.
      We have implemented improved culture conditions, including short incubation
      periods, by continually perfusing medium over producer cells in a packed-bed
      bioreactor incubated at 32 degrees C. By operating the packed-bed bioreactor in
      perfusion mode, retroviral vector supernatants with a high transduction
      efficiency can be routinely produced in large quantities.

PMID- 8750012
TI  - Inhibition of transfer of collagen-induced arthritis into SCID mice by ex vivo
      infection of spleen cells with retroviruses expressing soluble tumor necrosis
      factor receptor.
AB  - Collagen-induced arthritis can be transferred into severe combined
      immunodeficiency (SCID) mice by spleen cells from diseased DBA/1 mice. The
      development of arthritis in SCID animals can be prevented by infection ex vivo of
      DBA/1 spleen cells with retroviruses expressing the monomeric soluble human p75
      tumor necrosis factor (TNF) receptor (TNF-R). In addition, a vector engineered to
      express a polycystronic mRNA with TNF-R and the herpes simplex virus thymidine
      kinase (HSVtk) gene, while producing low levels of TNF-R, had a limited effect
      which could be blocked by treating the animals with ganciclovir. A retroviral
      vector expressing the HSVtk gene alone had no effect on this arthritis transfer
      model with or without ganciclovir. Serum levels of TNF-R did not correlate with
      clinical signs, however, lower anti-collagen antibody levels corresponded with
      lack of clinical symptoms. These results indicate that local production of
      cytokine inhibitor is essential for therapeutic purposes while systemic levels
      may not be required.

PMID- 8750013
TI  - Expression of factor VII by muscle cells in vitro and in vivo following direct
      gene transfer: modelling gene therapy for haemophilia.
AB  - Direct injection of plasmid DNA into skeletal muscle has been proposed as a
      method of effecting somatic gene therapy. This article describes the construction
      and testing of a plasmid derived expression cassette believed to confer skeletal
      muscle specific expression. Expression constructs were designed containing the
      full-length cDNAs for both coagulation factor VIII and factor VII. The engineered
      genes were flanked by two muscle specific regulatory elements from different
      myosin isoforms and by an artificial polyadenylation signal sequence. In vitro
      transfection of C2-myoblasts led to expression of the factor VIII gene, shown by
      reverse transcription and polymerase chain reaction, upon differentiation of the
      myoblasts. The expression of the FVII construct was tested in a C2 cell culture
      system and also when injected directly into mouse muscle. It was found that in
      cell culture the level of factor VII antigen outside the cell, ie in the cell
      culture medium was two- to three-fold higher than inside the cell, ie in the cell
      lysate. This level of expression was found to continue for the duration of cell
      culture maintenance and a fully functional protein was produced. In vivo
      transfection experiments in mice showed a substantial increase in factor VII
      antigen compared with the background level 4-5 days after injection. An anti
      human factor VII antibody was detected 7-10 days after injection. We conclude
      that muscle cells in vitro secrete and efficiently carry out post-translational
      modifications of the engineered gene product and in vivo secrete the gene product
      resulting in elevation of systemic levels. The data provide the basis for the use
      of muscle cells as an in vivo expression system for coagulation proteins in the
      treatment of inherited haemostatic and thrombotic disorders.

PMID- 8750014
TI  - The sparse fur mouse as a model for gene therapy in ornithine
      carbamoyltransferase deficiency.
AB  - The sparse fur (spf/Y) mouse was evaluated as a model for studying gene therapy
      in ornithine carbamoyltransferase deficiency (OCTD), the most common inborn error
      of urea synthesis. Previous studies have defined a number of biochemical
      characteristics of this animal model that are analogous to the human disease:
      OCTD in liver, elevated ammonium and glutamine, low citrulline and arginine in
      plasma, elevated urinary orotic acid excretion, neurochemical alterations and
      responsiveness to alternative pathway therapy. In this study, metabolic flux,
      survival, behavior and learning of these animals were examined in preparation for
      a trial of gene therapy. We found that, as has been previously reported, OCT
      activity in liver ranged from 10 to 20% of control. Yet, stable isotope studies
      using 15N ammonium chloride to follow ureagenesis in vivo showed 55% of normal
      urea synthetic capacity. This suggests that partial correction with gene therapy
      may be sufficient to normalize urea synthesis. Although it has been suggested
      that liver OCTD and its consequent metabolic effects normalize without treatment
      by adulthood in the spf/Y mouse, we did not find this to be the case. We
      documented that the spf/Y mouse had a markedly decreased lifespan (< 10% of
      normal) and remained runted throughout life. In terms of behavior, the spf/Y mice
      had evidence of decreased learning in a passive avoidance task that was not
      attributable to alterations in activity. These clearly definable metabolic and
      behavioral abnormalities suggest that the spf/Y mouse should prove a useful model
      for studying the efficacy of gene therapy in OCTD.

PMID- 8750015
TI  - Targeting of adenovirus penton base to new receptors through replacement of its
      RGD motif with other receptor-specific peptide motifs.
AB  - The adenovirus coat protein, penton base, contains the peptide motif RGD which
      mediates binding to the integrin cell surface receptors alpha v beta 3 and alpha
      v beta 5. These integrins then mediate adenovirus internalization. We have
      developed penton base chimeras that recognize tissue-specific integrin receptors
      by replacing the wild-type RGD peptide motif with alpha v beta 3- or alpha 4 beta
      1-specific peptide motifs. In one chimera the original haiRGDtfa motif was
      replaced with the peptide motif eiLDVpst which mediated chimera binding to the
      integrin alpha 4 beta 1. This integrin is expressed at high levels on lymphocytes
      and monocytes but is not expressed on epithelial or endothelial cells. In a
      second chimera the wild-type sequences flanking the RGD motif were altered to
      abrogate its interaction with alpha v beta 5 while retaining its specificity for
      alpha v beta 3. The integrin alpha v beta 5 is expressed primarily on epithelial
      cells whereas the integrin alpha v beta 3 is normally expressed on endothelial
      cells. The integrin alpha v beta 3 is also aberrantly expressed on certain
      metastatic melanomas and glioblastomas. A deletion mutant lacking the RGD
      sequence did not bind to any integrins. Such chimeras incorporated into
      adenovirus virions may be useful in targeting specific tissues in adenovirus
      mediated gene delivery.

PMID- 8750016
TI  - Expression of two H-2K genes, syngeneic and allogeneic, as a strategy for
      potentiating immune recognition of tumor cells.
AB  - Metastatic clones of some tumors manifest an impaired expression of class I major
      histocompatibility complex (MHC) antigens. High metastatic, low immunogenic Lewis
      lung carcinoma clones (C57BL-H-2b origin) express low levels of the H-2Kb MHC
      antigen. These cells metastasize spontaneously in C57BL/6J mice. Transfection of
      syngeneic or allogeneic H-2K genes converted such cells to the nonmetastatic
      state, but did not prevent the growth of the local tumors. Transfection of two H
      2K genes, syngeneic and allogeneic, into the highly metastatic clone D122,
      resulted in reduction of the growth rates of the transfectants and protected the
      mice from D122 metastases. In contrast, cells transfected with a single class I
      gene (syngeneic or allogeneic) gave partial protection, or did not protect the
      mice at all from D122 metastases. The combination of syngeneic and allogeneic
      genes in the same tumor cell elevated the immunogenic properties of the
      expressing cells and potentiated the immune response as was demonstrated by in
      vitro cytotoxicity analysis and by limiting dilution cytotoxicity analysis.
      Increased immunogenicity by double transfection may constitute an effective
      therapeutic modality.

PMID- 8750018
TI  - A packaging cell line for propagation of recombinant adenovirus vectors
      containing two lethal gene-region deletions.
AB  - A cell line that provides the E1 as well as the E4 gene functions of human
      adenovirus 5 has been established by introduction of the full-length Ad5 E4
      region into 293 cells. To avoid the E1A transactivation of the E4 gene
      expression, the E4 promoter was replaced by the mouse alpha inhibin promoter
      containing a cAMP response element. This cell line was used to generate E1/E4
      deleted adenovirus vectors containing a lacZ gene in the E1 region under the
      control of mouse pgk promoter. The titer and the lacZ gene expression of E1/E4
      deleted adenovirus vector were comparable to those of E1-deleted vectors.
      Evidence of cytopathic effect was absent following infection of nonpermissive
      cell lines with E1/E4-deleted adenovirus in vitro. Establishment of the 293-E4
      cell line and the generation of E1/E4-deleted adenovirus vectors may prolong gene
      expression in vivo and significantly improve the safety of adenovirus vectors for
      human gene therapy.

PMID- 8750017
TI  - Quantitative fluorescence measurements of chloride secretion in native airway
      epithelium from CF and non-CF subjects.
AB  - Functional assessment of the efficacy of CFTR gene transfer protocols in humans
      has previously involved measurement of in vivo potential difference. We have
      studied whether freshly obtained airway epithelial cells may provide suitable
      tissue for studies of in vivo gene transfer using fluorescent digital imaging
      microscopy. Nasal epithelial cells from non-cystic fibrosis subjects (n = 6) and
      from cystic fibrosis (CF) patients (delta F508: delta F508, n = 5) were obtained
      by brushing and loaded with 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ).
      Addition of the cAMP-agonists forskolin (20 microM) and 3-isobutyl-1
      methylxanthine (IBMX, 100 microM) produced an increased efflux of iodide from the
      cells which was significantly (P < 0.05) greater in non-CF than in CF cells.
      Efflux following addition of the calcium ionophore, ionomycin (100 microM) was
      similar in both non-CF and CF cells. Liposome-mediated transfection of CF nasal
      epithelial cells in vitro with CFTR-cDNA restored the cAMP-stimulated efflux to
      non-CF values. Bronchial epithelial cells from non-CF subjects showed responses
      to forskolin and ionomycin that were not different to those in non-CF nasal
      epithelia. These data demonstrate that the assay provides a useful method for
      assessing correction of abnormal ion transport in non-cultured CF epithelium and
      is likely to provide a further assay for assessment of in vivo gene transfer
      efficiency in protocols of gene therapy for CF.

PMID- 8750019
TI  - Receptor-mediated transfer of pSV2CAT DNA to mouse liver cells using asialofetuin
      labeled liposomes.
AB  - Asialofetuin-labeled liposomes (AF-liposomes) were developed as a nonviral vector
      having high transfection activity for receptor-mediated gene transfer to
      hepatocytes by systemic administration. Initially, the majority of pSV2CAT, a
      chloramphenicol acetyltransferase (CAT) gene expression plasmid, was associated
      with AF-liposomes (AF-liposome-pSV2CAT), and they were injected into the portal
      vein of an adult mouse. Significantly high CAT activity was observed in the
      liver. The CAT activity in the liver was further increased two-fold by using AF
      liposomes completely encapsulating pSV2CAT. Nonlabeled control liposomes, on the
      other hand, showed lower CAT activity in the liver than in the spleen or lung.
      The level of CAT mRNA reflected the CAT activity obtained by each liposome
      preparation in each tissue. Immunohistochemical staining showed that CAT was
      produced in a large number of parenchymal cells localizing in the periportal
      area. The plasmid encapsulated in the internal aqueous layer of the liposomes was
      effectively protected from environmental degradation. Thus, by administration
      into the blood circulation, AF-liposomes would be successfully incorporated into
      hepatocytes through receptor-mediated endocytosis, and the encapsulated plasmid
      would be transferred to the intracellular pathway.

PMID- 8750020
TI  - Expression and localization of CFTR in the rhesus monkey surface airway
      epithelium.

PMID- 8750021
TI  - Parkinson's disease affects automatic and spares intentional verbal learning. A
      stochastic approach to explicit learning processes.
AB  - We studied word list and paired associates learning in patients with idiopathic
      Parkinson's disease and normal controls by means of a two-stage stochastic model,
      which allows independent measurements of encoding, storage and retrieval
      abilities. We preliminarily ascertained that the model components were both
      sufficient and necessary to account for the overall performance of the subjects,
      and then compared the learning abilities between the two groups. Parkinson's
      disease patients were selectively impaired in identifying well-known engrams, for
      which learning is superfluous, and in automatic retrieval, namely in abilities
      that do not need attentional effort. By contrast, they were unimpaired in
      encoding and intentional retrieval, which require a purposeful effort. The
      automatic-voluntary dissociation of Parkinson's disease patients' motor behaviour
      is, therefore, paralleled by some features of their memory performance.

PMID- 8750022
TI  - Sparing of verbs and preserved, but ineffectual reading in a patient with
      impaired word production.
AB  - We report a patient who, following a left fronto-temporal lesion, showed a
      complete sparing of the semantic store and a deficit of word production
      characterized by two types of dissociations. First, oral and written output was
      severely disrupted in naming and partially impaired in repetition, writing to
      dictation and oral spelling, with the exception of verbs, which were normally
      produced in every modality and condition of stimulation. Second, reading was
      normal for all type of words as well as non-words. This pattern of deficits
      suggests two functional lesions, one affecting the connections between the
      semantic store and the phonological lexicon and the other damaging the sublexical
      route that converts sound to sound and sound to print. It also implies that words
      are independently organized in the phonological lexicon, based on their
      grammatical class and have discrete connections with the semantic store. However,
      CT scan evidence does not support the hypothesis that this functional
      dissociation finds its anatomical correlate in the specialization of the frontal
      premotor cortex for verbs and the antero-medial temporal cortex for nouns. In
      spite of his normal reading performance, both in terms of comprehension and of
      accuracy and speed in word production, the patient complained that he met with
      great difficulty in reading newspapers and books, to the point that he had to
      renounce to this previously favourite activity. It was found that it took him
      time and effort to grasp the meaning of complex sentences and passages and it was
      speculated that, contrary to single words and elementary sentences, comprehension
      of this type of material cannot be achieved by the mere access of orthographic
      stimuli to semantics, but requires the retrieval of word-forms. It would appear
      that a patient, whose lexical route is blocked, can only read passages, by first
      converting print to sound via the sublexical route and then re-entering the
      semantic store with oral input.

PMID- 8750023
TI  - A reverse length effect in dysphasic naming: when elephant is easier than ant.
AB  - When the influence of length on picture naming in dysphasia has been investigated
      in the past, studies tend to show worse performance with longer items (or no
      influence of stimulus length). This paper describes a man with dysphasia who is
      better at labelling pictures with long names than with short names: he
      demonstrates a reverse length effect. Three models which incorporate an output
      component are described. The details of the case study are given and discussed in
      relation to the predictions of these models regarding target length. This leads
      onto further predictions from one model (Butterworth, 1989) which are tested
      against the data.

PMID- 8750024
TI  - A new case of retrograde amnesia with abnormal forgetting rate.
AB  - The classic amnesic syndrome is characterised by a severe anterograde amnesia and
      a less important retrograde amnesia with sparing of the semantic component. We
      report the case of a patient who showed a global amnesic syndrome following a
      mild head injury. Initially, amnesia was both anterograde and retrograde, and
      also involved semantic knowledge. Two years later the picture had changed
      remarkably. The retrograde deficit for autobiographical events was still total,
      while semantic memory had recovered to a large extent. Learning had also greatly
      improved, but only if assessed after a short delay; abnormally rapid forgetting
      rate were found at longer intervals. This pattern of impairment does not lend
      itself to an easy interpretation. However, the hypothesis of a consolidation
      deficit may be advanced.

PMID- 8750025
TI  - Optokinetic stimulation affects both vertical and horizontal deficits of position
      sense in unilateral neglect.
AB  - The effects of optokinetic stimulation on the disorders of position sense in the
      horizontal and vertical planes were assessed in 24 patients with unilateral
      cerebral lesions (eight right brain-damaged patients with visuo-spatial
      hemineglect, eight right brain-damaged patients without neglect, eight left brain
      damaged patients without neglect). In neglect patients, the position sense
      disorder was more severe, and affected by optokinetic stimulation in a direction
      specific fashion. In both the horizontal and the vertical plane, and in both
      arms, stimulation with a direction of the movement contralateral to the side of
      the lesion improved the disorder, whereas stimulation with an ipsilateral
      direction worsened the deficit. The suggestion is made that in patients with
      neglect the disorder of position sense is produced, at least in part, by an
      ipsilateral distortion of an egocentric co-ordinate system, comprising both the
      horizontal and the vertical dimension, which may be affected by direction
      specific optokinetic stimuli.

PMID- 8750026
TI  - The influence of target perturbation on manual aiming asymmetries in right
      handers.
AB  - Ten right-handed subjects performed 100 target-aiming movements with each hand.
      These movements were directed toward a small target on the midline. On 60% of the
      trials, the target remained stationary. On other randomly placed trials, the
      target "jumped" to a location 3 cm to the right (20%) or left (20%) of its
      original position when the cursor had travelled 6.5 cm. Although no hand
      differences were evident in the control condition, the right hand acquired the
      new target location more quickly than the left hand when the target was perturbed
      in either direction. Kinematic data revealed that this advantage was not due to
      initiating an adjustment to the initial movement more rapidly, but rather less
      time decelerating the corrective movement. Movement adjustments on perturbed
      trials were implemented more rapidly in left space than right space independent
      of the hand doing the aiming. These asymmetries may reflect the differential role
      of the two cerebral hemispheres in the control of goal-directed movements.

PMID- 8750027
TI  - Cross-form priming in normal aging and in mild dementia of the Alzheimer type.
AB  - Twenty patients at early stages of Alzheimer's disease (AD), 20 elderly control
      subjects and 20 young subjects completed a cross-form priming task, followed by a
      free recall task. Results show that patients with mild AD display priming
      effects, and that these priming effects are strictly comparable to those obtained
      by elderly and young control subjects. Moreover, while the patients' performances
      are normal in the implicit part of the task, they are massively impaired in the
      explicit free recall task. These results don't support the hypothesis of a
      dissociation of performances between identification tasks and generation tasks in
      Alzheimer's disease, and show that conceptual priming can be observed at early
      stages of the disease, despite semantic memory impairments.

PMID- 8750028
TI  - Differential effects of line length on bisection judgements in hemispatial
      neglect.
AB  - Recent studies have shown that certain symptoms of spatial neglect are co
      determined by two major factors: one whose general nature is perceptual, the
      other whose nature is directional and/or motor. In the present study, patients
      whose neglect was classified as predominantly 'perceptual' or 'directional'
      through use of the Landmark task (Milner, Brechmann and Pagliarini, 1992) were
      asked to bisect lines ranging in length from 20 to only 2.5 cm. It was found that
      the one patient with predominantly directional neglect showed large rightward
      errors at all line lengths. In contrast, those with perceptual neglect made very
      small (usually leftward) errors on short lines. It is argued that it is essential
      to separate these different subtypes of neglect patient if we are to understand
      the causation of their behaviour in tasks such as line bisection.

PMID- 8750029
TI  - Verbal skills in relatives of autistic females.
AB  - First-degree relatives of 26 autistic females and 26 Down's syndrome females were
      tested on a battery of verbal tasks designed to detect subtle anomalies. No
      differences were found when comparing parents of the two groups, but there was a
      significant difference between siblings. This result was accounted for by a lower
      performance of the brothers of autistic subjects. The verbal scores of the
      relatives, either parents or siblings, were not related to the IQ of the proband.
      Findings are discussed in relation to the hypothesis of genetic and/or
      environmental factors in autism.

PMID- 8750030
TI  - Different components in word-list forgetting of pure amnesics, degenerative
      demented and healthy subjects.
AB  - This study investigated the contribution of different components of the serial
      position curve to the accelerated forgetting rate displayed by amnesic and
      degenerative demented patients in word-list recall. For this purpose, we analyzed
      immediate and 15 min delayed recall performances on Rey's 15-word learning task
      of 16 pure amnesic, 15 Alzheimer's demented and 81 healthy subjects. Results
      documented that in all groups most forgetting occurred at the expense of terminal
      items of the word list. Nevertheless, both amnesic and demented patients showed a
      disproportionately larger memory loss on the recent part of the serial position
      curve than healthy subjects. Finally, amnesics (but not AD patients) suffered
      from a significantly larger forgetting rate for primacy items than normal
      controls. These data demonstrate that a critical deficit in memory disordered
      patients is represented by a failure in transferring information from a
      transitory memory status to a more durable storing condition. At least in amnesic
      patients, our results also suggest "true" long-term forgetting, presumably due to
      decay or to the intervening inaccessibility of previously stored memory
      representations.

PMID- 8750031
TI  - Consonant harmony as a compensatory mechanism in fluent aphasic speech.
AB  - This study addresses how fluent aphasics construct complete phonological
      representations, given the premise that their phonological speech errors result
      from faulty information about stored lexical representations. We explored whether
      consonant harmony, a common rule-governed process of feature copying, operates as
      a compensatory device for completing phonological representations in fluent
      aphasia. This was examined in a corpus of phonemic paraphasias (n = 543) produced
      by 8 fluent aphasics during picture naming. Consonant substitutions due to a
      single feature change (n = 143) were analyzed for the properties of consonant
      harmony predicted by the phonological principles embodied in a Universal
      Markedness version of Underspecification Theory (e.g., Chomsky and Halle, 1968).
      Results indicated that harmony constrained the feature substitution errors
      involving the feature class of voice (e.g., calendar-->/[symbol: see text]/), but
      not place of articulation (e.g., igloo-->/idlu/); substitutions due to an error
      in manner were rare. These findings were used to argue that for English-speaking
      fluent aphasics a consonant harmony rule for the feature voice is incorporated
      into a compensatory output mechanism that is used to complete faulty lexical
      phonological representations.

PMID- 8750032
TI  - Factoring handedness data: I. Item analysis.
AB  - Recently in this journal Peters and Murphy challenged the validity of factor
      analyses done on bimodal handedness data, suggesting instead that right- and left
      handers be studied separately. But bimodality may be avoidable if attention is
      paid to Oldfield's questionnaire format and instructions for the subjects. Two
      characteristics appear crucial: a two-column LEFT-RIGHT format for the body of
      the instrument and what we call Oldfield's Admonition: not to indicate strong
      preference for handedness item, such as write, unless "... the preference is so
      strong that you would never try to use the other hand unless absolutely forced
      to...". Attaining unimodality of an item distribution would seem to overcome the
      objections of Peters and Murphy. In a 1984 survey in Boston we used Oldfield's
      ten-item questionnaire exactly as published. This produced unimodal item
      distributions. With reflection of the five-point item scale and a logarithmic
      transformation, we achieved a degree of normalization for the items. Two surveys
      elsewhere based on Oldfield's 20-item list but with changes in the questionnaire
      format and the instructions, yielded markedly different item distributions with
      peaks at each extreme and sometimes in the middle as well.

PMID- 8750033
TI  - Coordinate frames for naming misoriented chimerics: a case study of visuo-spatial
      neglect.
AB  - A persistent line of inquiry for the students of visuo-spatial neglect has
      involved the perceptual frame of reference respect to which the neglected region
      of space is defined. On standard testing conditions viewer-centered and object
      centered systems of coordinates are confounded. In order to disambiguate these
      two reference frames FB, a patient with severe left visual neglect consequent
      upon a right parieto-temporal haemorrhage, was asked to identify chimeric figures
      presented at different orientations. FB continued to recognize poorly the left
      side of chimeric figures even when the display was rotated 90 degrees clockwise
      or anticlockwise so that the 'left' of the chimeric fell on the patient's
      egocentric up or down, respectively. The result suggests that, at least under the
      present testing conditions, unilateral neglect is tied to the principal (top
      bottom) axis of the object. Object-centered vs. (viewer-centered)
      representational accounts of this finding are discussed.

PMID- 8750034
TI  - Hand motor performance and degree of asymmetry in monozygotic twins.
AB  - To determine whether the absolute degree of asymmetry of hand motor performance
      (irrespective of direction of this asymmetry) may have a heritable component we
      examined 20 pairs of monozygotic (MZ) twins of whom 10 pairs were concordantly
      right-handed (MZ-RR) and 10 pairs discordant for handedness (MZ-RL). The tests
      comprised measurements of the maximum left and right hand tapping rate as well as
      a paper-and-pencil test of left and right hand motor proficiency. Intraclass
      correlations within MZ-RR and MZ-RL for absolute degree of hand motor asymmetry
      were not significant. In contrast, significant intrapair correlations emerged for
      overall hand motor performance, a measure unrelated to laterality. These results
      demonstrate that at least in MZ twins the degree of hand motor asymmetry is
      mainly determined by non-genetic factors, whereas overall hand motor skill is
      more likely to be influenced by the genome. In addition, the lack of a difference
      in overall hand motor performance between MZ twins and 40 singletons studied as
      controls would not support hypotheses explaining behavioural asymmetry in twins,
      or their discordance for asymmetry, by developmental dysfunction.

PMID- 8750035
TI  - Development of the glutamate, GABA, and dopamine systems in relation to NRH
      induced neurotoxicity.

PMID- 8750036
TI  - Age-specific neurotoxicity in the rat associated with NMDA receptor blockade:
      potential relevance to schizophrenia?
AB  - Agents that block the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor
      induce a schizophrenialike psychosis in adult humans and injure or kill neurons
      in several corticolimbic regions of the adult rat brain. Susceptibility to the
      psychotomimetic effects of the NMDA antagonist, ketamine is minimal or absent in
      children and becomes maximal in early adulthood. We examined the sensitivity of
      rats at various ages to the neurotoxic effects of the powerful NMDA antagonist,
      MK-801. Vulnerability was found to be age dependent, having onset at
      approximately puberty (45 days of age) and becoming maximal in early adulthood.
      This age-dependency profile (onset of susceptibility in late adolescence) in the
      rat is similar to that for ketamine-induced psychosis or schizophrenia in humans.
      These findings suggest that NMDA receptor hypofunction, the mechanism underlying
      the neurotoxic and psychotomimetic actions of NMDA antagonists, may also play a
      role in schizophrenia.

PMID- 8750037
TI  - Combined dexamethasone/corticotropin-releasing hormone test in acute and remitted
      manic patients, in acute depression, and in normal controls: I.
AB  - Hypothalamic-pituitary-adrenal system (HPA)-function in patients with mania (n =
      11), depression (n = 11, unipolar) and in control subjects (n = 11) was studied;
      six of the acutely manic patients were reevaluated after a symptom-free interval
      of at least 6 months. The combined dexamethasone-suppression/human CRH-challenge
      test was used to probe HPA-system function. After CRH and dexamethasone
      pretreatment, ACTH and cortisol release were significantly increased in both
      manic and depressed patients in comparison to the control group. In the remitted
      patients with mania, a significant decrease in hormonal release after DEX and CRH
      was evident when compared to the acute manic episode, but the degree of CRH
      stimulated hormone secretion in these remitted patients was still significantly
      larger than in normal controls. This study demonstrates that acute and remitted
      manic episodes are associated with a profoundly dysregulated HPA-system activity.

PMID- 8750038
TI  - Combined dexamethasone/corticotropin-releasing hormone test in patients with
      schizophrenia and in normal controls: II.
AB  - Hypothalamic-pituitary-adrenal system (HPA) function was tested in 24 patients
      with schizophrenia and compared to 24 age-matched healthy volunteers using the
      combined dexamethasone-suppression (DST/CRH) corticotropin-releasing hormone
      stimulation test (DST/CRH). After stimulation with CRH, the dexamethasone
      pretreated patients released significantly more cortisol, but a similar amount of
      adrenocorticotropic hormone (ACTH) in comparison to controls. No association
      between DST status and degree of severity of illness and/or current medication
      was found. However, in comparison to unmedicated patients, those patients
      currently receiving antipsychotics, who were also those with a lesser degree of
      severity of illness, showed a decreased release of CRH-stimulated cortisol and
      ACTH. This study demonstrates that schizophrenic patients have a dysregulation of
      the HPA system as assessed with the DEX/CRH test. Overall, however, the degree of
      HPA-system dysfunction in schizophrenic patients seems to be of a lesser
      magnitude than in patients with affective disorders.

PMID- 8750039
TI  - Genetic heterogeneity may in part explain sex differences in the familial risk
      for schizophrenia.
AB  - The purpose of this study was to attempt, in part, to explain significant sex
      differences in the familial risk (FMR) for schizophrenia found in previous
      studies. We hypothesized that, like probands, relatives of male vs. female
      probands may express different forms or subsyndromal symptoms of schizophrenia,
      i.e., differential expression of flat affect. Studied were 332 schizophrenic
      probands defined by Diagnostic and Statistical Manual of Mental Disorders, 3rd
      ed. (DSM-III), criteria and 725 first-degree relatives from well-known
      retrospective cohort family studies. Results showed that relatives of male
      probands were at significantly higher risk for expressing flat affect than
      relatives of female probands, which did not hold for relatives of normal
      controls. Logistic regression was used to show that when flat affect was
      incorporated into the definition of affected among relatives, sex differences in
      FMR disappeared.

PMID- 8750040
TI  - Prophylactic estrogen in recurrent postpartum affective disorder.
AB  - Seven women with histories of puerperal psychosis and four with histories of
      puerperal major depression were consecutively treated with high-dose oral
      estrogen immediately following delivery. None of the women had histories of
      nonpuerperal affective disorder, and all women were affectively well throughout
      the current pregnancy and at delivery. Despite the high risk for recurrent
      illness in this population, only one woman developed relapse of postpartum
      affective disorder. All others remained entirely well and required no treatment
      with psychotropic medications during the 1 year follow-up period. This low rate
      of relapse, 9% compared to an expected 35-60% without prophylaxis, suggests that
      oral estrogen may stem the rapid rate of change in estrogen following delivery,
      thereby preventing the potential impact on dopaminergic and serotonergic
      neuroreceptors. It is hypothesized that the rapid rate of change of estrogen
      after delivery creates an "estrogen withdrawal state." This may be a critical
      factor in driving acute puerperal affective psychosis and early-onset puerperal
      major depression.

PMID- 8750041
TI  - Plasma norepinephrine kinetics in patients with posttraumatic stress disorder.
AB  - To determine whether basal sympathetic nervous system (SNS) function is increased
      in patients with posttraumatic stress disorder (PTSD), we used a radioisotope
      dilution technique to assess basal arterialized plasma norepinephrine (NE)
      kinetics in 12 men who were Viet Nam combat veterans with PTSD and six normal
      controls. In addition to determining the rates of appearance of NE into, and
      clearance of NE from, plasma, we measured basal arterialized plasma levels of
      epinephrine (EPI), and also vital signs, in both groups. Patients with PTSD
      actually manifested lower arterialized plasma levels of NE, and had lower rates
      of appearance of NE into plasma, than did controls. The rate of NE clearance from
      plasma was unaltered in PTSD patients. Patients with PTSD also showed a trend
      toward lower arterialized EPI levels than controls, but manifested a trend toward
      higher diastolic blood pressure. Our data indicate that basal SNS activity is not
      increased in patients with PTSD and that previous reports of increased resting
      SNS activity in this population may instead reflect SNS reactivity.

PMID- 8750042
TI  - Instructional set does not alter outcome of respiratory challenges in panic
      disorder.
AB  - In an attempt to reproduce the findings of Rapee et al (1986) that instructional
      set could alter the anxiogenic effects of carbon dioxide inhalation, 45 patients
      with panic disorder received two sets of instructions and then underwent a series
      of respiratory challenges (room air hyperventilation, 5% and 7% CO2 inhalation).
      The instructions failed to alter the anxiogenic response to any of the
      interventions.

PMID- 8750043
TI  - Polygraphic sleep measures differentiate alcoholics and stimulant abusers during
      short-term abstinence.
AB  - We hypothesized that stimulant abusers would sleep more and have more rapid eye
      movement (REM) sleep than primary alcoholics during acute withdrawal (first 10
      days drug free) but would have opposite patterns during subacute withdrawal (days
      11-14 drug free). We compared polygraphic sleep patterns during acute withdrawal
      (days 3-10) for 7 stimulant abusers and 8 alcoholics and during subacute
      withdrawal (days 11-14) for 7 different stimulant abusers and 8 different
      alcoholics. For comparison purposes, a group of normal controls from our
      preexisting database were matched for age and gender. Two statistically
      significant interactions were found: consistent with our hypothesis, stimulant
      abusers showed greater total sleep (TST) and REM sleep during acute withdrawal
      than subacute withdrawal, compared with alcoholics. In contrast, alcoholics
      showed less TST and REM sleep during acute withdrawal than during subacute
      withdrawal. Our polygraphic sleep data support the hypothesis that physiological
      withdrawal differs in alcoholics compared with stimulant abusers. Different
      mechanisms may underlie withdrawal in these two substances.

PMID- 8750044
TI  - Generalization, duration, and low-frequency electroencephalographic persistence
      of bilateral electroconvulsive therapy seizure.
AB  - Measurements were made at the beginning and end of a course of bifrontotemporal
      brief-pulse ECT for 28 males to both determine how well seizure generalization is
      maintained along the course of electroconvulsive therapy (ECT) and examine
      correspondence between low-frequency EEG activity and other seizure durations.
      Durations of spike electroencephalographic (EEG) paroxysmal activity, heart rate
      elevation, and Ionic-clonic activity decreased about 30% along the course, p <
      0.0001, yet correlated highly at both times, I = 0.69 to 0.88, p < 0.0005, as did
      their changes: these correlations demonstrate high-seizure generalization and its
      maintenance. EEG low-frequency persistence, the difference between total and
      spike EEG paroxysmal durations, doubled along the course (p = 0.041), but showed
      no association with any other seizure duration measure. This absence of
      association suggests that low-frequency activity and other seizure duration
      measures describe separate phenomena and should be expressed separately, rather
      than combined as the (traditional) total EEG paroxysmal duration.

PMID- 8750045
TI  - Haloperidol does not affect the level of serum-soluble interleukin-2 receptor in
      drug-free male schizophrenics.

PMID- 8750046
TI  - Age-related MRI abnormalities in bipolar illness: a clinical study.

PMID- 8750047
TI  - Comparison of home and laboratory based monitoring of NPT using the Rigiscan; a
      preliminary report.
AB  - Laboratory based and home based monitoring of nocturnal penile tumescence (NPT)
      with the Rigiscan device was compared in a consecutive series of 100 men
      monitored in the laboratory, and a further consecutive series of 100 men
      monitored at home. Recordings at home were significantly shorter and involved
      more interruptions than laboratory based records. With subgroups, matched for
      diagnosis or the reporting of waking erections as well as age, laboratory
      monitoring tended to produce more sustained erections. However, in spite of the
      matching of subgroups, this trend may have resulted from aetiological rather than
      methodological differences, and further comparison of the two methods in the same
      subjects is now warranted. In the meantime, home monitoring should be used with
      diagnostic caution.

PMID- 8750048
TI  - Nitric oxide synthase and vasoactive intestinal polypeptide colocalization in
      neurons innervating the human penile circulation.
AB  - The question which neurotransmitters mediate penile erection in humans is still
      unsettled. Although functional studies have established a role of vasoactive
      intestinal polypeptide (VIP) and nitric oxide (NO) in human penile smooth muscle
      relaxation, they did not allow a conclusion as to whether they are released by
      neurons or other cells. This article outlines the identification of numerous
      nitric oxide synthase (NOS) and VIP-containing axons in the human penis. More
      than 50% of the perivascular nerve fibres and more than 90% of the trabecular
      nerve fibres within the corpus cavernosum stained positive for both NOS and VIP.
      In contrast, endothelial cells stained only faintly for NOS-immunoreactivity,
      NOS/VIP-immunoreactivity was reduced (diabetes) or absent (lesion of the
      cavernous nerve) in penile tissue taken from patients with neurogenic impotence.
      These findings support the concept that NO and VIP act as neural comediators of
      penile erection in humans.

PMID- 8750049
TI  - Deep dorsal vein arterialization in arteriogenic impotence: use of the dorsal
      artery as a neoarterial source.
AB  - Deep dorsal vein (DDV) arterialization has developed as a treatment option for
      patients with arteriogenic impotence, especially in situations where artery-to
      artery bypass is not feasible. The inferior epigastric artery (IEA), harvested
      through a lower abdominal incision, has usually served as the neoarterial source.
      Using dynamic infusion cavernosometry and cavernosography (DICC) to evaluate
      arterial and venous erection factors and pudendal arteriography to define
      arterial anatomy, we have identified 16 patients with cavernosal artery (CA)
      obstruction and a normal dorsal artery (DA) to serve as the neoarterial source.
      All patients were less than 50 years old (mean 34.8 +/- 8.6 years). During DICC,
      the gradient between systemic and CA systolic occlusion pressures averaged 38.7
      mmHg. Two patients showed moderate and two minimal corporal veno-occlusive
      dysfunction (CVOD). From 1991-94, all 16 underwent microscopic DA-DDV
      arterialization. Four of these patients also underwent venous ligation procedures
      and three had IEA bypass to the other DA. With adequate follow-up in 15 men, the
      results for six are considered excellent or normal (40%); eight improved (53.3%)
      and one was unchanged. In the improved group are three men who did not respond
      adequately to maximum penile injection therapy before surgery but used small
      doses afterward with success. Of the three smokers in the series, two were
      improved and one unchanged. Excellent results were found in four of five men
      (80%) under age 30 but only one of five (20%) over age 40. Complications included
      two instances of penile shortening and one of glans hyperemia requiring
      reoperation. By avoiding an abdominal approach, operative times, morbidity and
      recovery were substantially shortened. This operative approach can provide an
      excellent treatment for nonsmokers with CA obstruction and a normal DA.

PMID- 8750050
TI  - Chronic penile denervation in the rat: effect on cavernous tissue morphology and
      function.
AB  - We evaluated the effects of chronic penile denervation on cavernous tissue
      morphology and function in 36 Sprague-Dawley rats. At age seven weeks, 18 animals
      underwent bilateral cavernous nerve neurectomy: 18 animals underwent sham
      operation as a control. A functional, biochemical and morphological assessment of
      the rats' penises was performed at 4 months. In denervated rats, intracavernous
      pressure failed to rise with electrostimulation of the pelvic plexus. However, a
      normal rise in pressure was found with direct intracavernous injection of sodium
      nitroprusside and papaverine. Sodium dodecylsulfate polyacrylamide (SDS) gel
      electrophoresis of the penile homogenate showed subtle differences between
      denervated and control animals. Based upon the histological findings there was no
      difference in staining of the cavernous tissue for acetylcholinesterase- and
      catecholamine-positive nerve fibers between experimental and control animals,
      since the innervation density was not quantified and the number of fibers was not
      counted. We conclude that chronic cavernous nerve neurectomy does not cause
      significant morphological or functional changes to the penile erectile tissue of
      rats.

PMID- 8750051
TI  - Permanent open shunt as a reason for impotence or reduced potency after surgical
      treatment of priapism in 26 patients.
AB  - A permanent open shunt as a cause of impotence or impaired potency after a shunt
      operation for priapism is an unusual situation. In this series we studied the
      persistence of an open shunt in 26 patients who had developed impotence or
      impaired potency after operative treatment for priapism. All patients had been
      examined by cavernosography on the suspicion of an open shunt, giving a positive
      finding in five of 26 cases, in all of which impotence was cured by closure of
      the shunt. In five patients without a permanent open shunt potency returned to
      normal only after 6-12 months.

PMID- 8750052
TI  - Clinical efficacy of Korean red ginseng for erectile dysfunction.
AB  - To investigate the efficacy in treating erectile dysfunction and to develop a
      natural drug without complications, the results of ginseng treatments are
      compared to placebo and other drug. A total of 90 patients with 30 patients in
      each group were closely followed. Changes in symptoms such as frequency of
      intercourse, premature ejaculation, and morning erections after treatment were
      not changed in all three groups (p > 0.05). However in the group receiving
      ginseng, changes in early detumescence and erectile parameters such as penile
      rigidity and girth, libido and patient satisfactions were significantly higher
      than that of other groups (p < 0.05). The overall therapeutic efficacies on
      erectile dysfunction were 60% for ginseng group and 30% for placebo and trazodone
      treated groups, statistically confirming the effect of ginseng (p < 0.05). No
      complete remission of erectile dysfunction was noted, but partial responses were
      reported. No cases of aggravation of symptoms were reported. AVS-penogram, which
      is a recording of penile hemodynamic changes during the natural erection after
      audiovisual erotic stimulation, is not changed after administration of ginseng.
      However if administered for a prolonged period of time, the cummulative effect on
      vascular flow might be seen. The administration of Korean red ginseng has shown
      to have superior effects compared to the placebo or trazodone. Definitely more
      researches are required to elucidate the mechanism of ginseng. The effects of
      saponin, extracted from ginseng, on smooth muscle of erectile tissues, can be
      evaluated using organ chamber or nitric oxide titration, thereby pinpointing the
      exact action mechanism of saponin. As more informations are available, possible
      breakthrough in treatment of erectile dysfunction could be arisen from active
      saponin extracted from red ginseng, bringing hopes to many sufferers of erectile
      dysfunction.

PMID- 8750053
TI  - Metabolic responses of rabbit corpus cavernosum tissue to various forms of
      stimulation.
AB  - The present study was designed to investigate the effect of various forms of
      stimulation on the levels of high energy phosphates (ATP + CP) in the rabbit
      corpora cavernosa. Prestimulation with the alpha agonist phenylephrine (200
      microM) for five minutes caused a significant decrease in both ATP and Creatine
      phosphate (CP) when compared with control tissue. Field stimulation (64 Hz) of
      the precontracted tissue induced an immediate decrease in tension by
      approximately 50%. The level of ATP + CP after field stimulated-relaxation was
      not significantly different from that from the initial prestimulation. Field
      stimulation (FS) from basal tone (2 g) caused a contraction and a significant
      decrease in both ATP and CP. Phentolamine (10 microM) (alpha-adrenergic
      antagonist) induced a significant decrease in the 2 g basal tension and a
      significant increase in the intracellular concentrations of both ATP and CP from
      that of control levels. In summary, the contractile response to both neuronal and
      pharmacologic stimulation was similar to that of other smooth muscle, producing a
      decrease in high energy phosphates. Field stimulated relaxation did not change
      the level of high energy phosphates from that of prestimulated levels. Finally,
      our data indicates that in the presence of the alpha blocker phentolamine (10
      microM), high energy phosphate levels (ATP + CP) increase significantly. This
      indicates that in the corpus cavernosum, there is significant basal tone that is
      linked to significant tonic alpha receptor stimulation and is maintained by a net
      consumption of ATP.

PMID- 8750054
TI  - Apoptosis.

PMID- 8750055
TI  - Immunogenicity of Vi capsular polysaccharide vaccine evaluated for three years in
      Korea.
AB  - The immunogenicity of a single dose of Salmonella typhi(S.typhi) Vi capsular
      polysaccharide(CPS) vaccine was evaluated before, and at 1, 3, 12, and 36 months
      after vaccination. Eighty-five adults(20-28 years of age) and sixty-four
      children(8-16 years of age) received a single dose of 25 micrograms Vi CPS
      vaccine intramuscularly, and antibody titers to Vi CPS were measured by passive
      hemagglutination. Of 149 vaccinees, 138(92.6%) showed seroconversion at 1 month
      after vaccination, and then 138 out of 141(97.9%) did at 3 months. Of 137
      vaccinees, 116(84.7%) maintained a persistent rise in Vi antibody titer 12 months
      after vaccination, and 55 out of 100(55.0%) had a 4-fold or greater rise at 36
      months. No significant adverse reactions were observed. Booster injection may be
      needed 3-5 years after vaccination.

PMID- 8750056
TI  - Expression of low density lipoprotein receptors in lymphoblasts induced by anti
      CD3 antibody in patients with hypercholesterolemia.
AB  - Familial hypercholesterolemia(FH) is a disease based on defects of low-density
      lipoprotein receptors(LDL-R). To interrupt and control the natural course of this
      disease, early identification of these patients is important. The routine lipid
      profile tests for hypercholesterolemia can not differentiate objectively FH from
      secondary hypercholesterolemia. The exact diagnosis of FH heterozygotes is
      especially essential because it is easier to develop premature coronary heart
      diseases compared with secondary hyper-cholesterolemia. A simplified rapid and
      precise method for the mass screening of FH patients and the differentiation
      between FH heterozygote and secondary hyperlipidemia was needed. For the test,
      lymphocytes were used as target cells in LDL-R assay. After a 5 day culture with
      anti-CD3 Ab as a mitogen, indirect immunofluorescence stain and flow cytometric
      analysis were applied. The results were as follows; 74 +/- 9% of the stimulated
      lymphoblasts from normal controls expressed LDL-R activity. Cultured, but
      unstimulated, lymphocytes of normal controls showed 27 +/- 8% positivity and
      total cultured lymphocytes showed positivity of 46 +/- 11% positivity.
      Lymphoblasts, unstimulated lymphocytes, and total cultured lymphocytes from hyper
      cholesterolemia without FH showed 74 +/- 10%, 25 +/- 10% and 50 +/- 17%,
      respectively, which showed no significant differences from normal control groups.
      FH Heterozygotes showed LDL-R positivity, 21 +/- 11% in lymphoblasts, 11 +/- 6%
      in unstimulated lymphocytes and 18 +/- 7% in total cultured lymphocytes. These
      data imply that adequately stimulated lymphocytes might be used for detecting
      defects in LDL-R and used to differentiate FH from secondary
      hypercholesterolemia.

PMID- 8750057
TI  - Expression of interleukin-6 in polymorphic reticulosis--immunohistochemical study
      of 5 cases.
AB  - Peripheral T cell lymphoma encompasses lymphomas with a variety of histologic
      appearances and clinical patterns. Recently, it has been suggested that almost
      all of the histologic features described under the name of polymorphic
      reticulosis(PR), lethal midline granuloma, and midline malignant reticulosis can
      be included in those generally described for malignant lymphomas of peripheral T
      cell origin(PTCL). There have been few studies of pathogenesis or tissue damage
      mechanism in PR patients. The need for a precise mechanism for tissue damage has
      important therapeutic implications. Using immunohistochemical methods with
      polyclonal anti IL-6 antibody, the authors describe 5 cases of PR with clinically
      and pathologically typical PR demonstrating a high expression of IL-6. According
      to classification, 2 cases of grade 1 PR showed the highest expressions, and 2
      cases of grade 2 PR with atypical lymphoid cells showed moderate activity, but
      one case progressed into frank lymphoma(grade 3) and lost IL-6 expression. This
      strongly implies that some cases of PR have a different mechanism of tissue
      damage from frank PTCL, despite the one disease spectrum. Further studies on more
      cases may help clarify the pathogenesis.

PMID- 8750058
TI  - The value of Helicobacter pylori IgG antibody in estimating the severity of
      gastritis in children.
AB  - A serologic test for antibodies is useful for diagnosis of Helicobacter
      pylori(H.pylori) infection in children. We evaluated the reliability of H.pylori
      IgG antibody titer in grading the severity of infection in children. We surveyed
      the sero-prevalence of H.pylori infection in 300 healthy school children (13 to
      15 years old). Thirty-four percent(102 of 300 children) were sero-positive for
      H.pylori. Of the 102 sero-positive children, 70 underwent gastroscopic
      examination. Ninety percent of sero-positive children(63 of 70 children) were
      proven to be H.pylori infected. All children with H.pylori infection had
      histologically proven gastritis, and its severity did not correlate with the IgG
      antibody titer. Although a serologic test is useful to identify H.pylori
      infection in children, it can not predict the severity of H.pylori associated
      gastritis.

PMID- 8750059
TI  - Expression of HLA-DR antigen in large bowel carcinoma.
AB  - One hundred large bowel carcinomas were studied immunohistochemically with regard
      to expression of HLA-DR antigen (DR). One or two sections from each tumor
      including surrounding normal mucosa were examined by a semiquantitative counting
      system for tumor cells and mucosal and stromal infiltrates of lymphocytes and
      mononuclear cells (MNCs) with DR expression and the results were applied Chi
      square test. The rate of presence of DR positive (DR+) lymphocytes in lymphoid
      nodules and DR+ lymphocytes/ MNC in the adjacent mucosa and stroma in DR+
      carcinoma (50%) was higher (P < 0.01) than in DR- carcinoma (21.9%). Thirty-six
      carcinomas (36%) were DR+. Three (75%) out of 4 DR+ poorly differentiated
      carcinomas and six (20%) out of 30 DR+ moderately differentiated carcinomas
      showed homogeneously strong DR+ expression. There was tendency for poorly
      differentiated carcinoma to be more homogeneous DR+ expression. According to
      Dukes' stage, four (80%) out of 5 carcinomas in Dukes' stage D were DR-. An
      increased infiltration of lymphocytes/MNCs into adjacent mucosa and stroma in
      large bowel carcinomas is possibly related with DR expression by carcinoma. From
      the results of this study, we postulated as follows: 1) DR+ tumor cells may act
      as antigen-presenting cells, 2) They may have an inhibitory effect for distant
      metastasis, 3) Poorly differentiated carcinoma expressed more DR+ homogeneously.

PMID- 8750060
TI  - Correlation between proliferating index and prognostic factors in papillary
      cystic tumors of the pancreas.
AB  - Fifteen cases of papillary cystic tumor of the pancreas (PCTP) were studied (14
      female patients, one male patient; mean age: 23.5 years). Most tumors developed
      in the head of the pancreas as a well circumscribed large mass. The tumor had a
      mean diameter of 6.7 cm(range; 2 to 15 cm). Histopathologically abundant delicate
      papillary fragments, monomorphic tumor cells and degenerative changes of the
      solid area of the tumor were characteristic. All but two cases had completely
      circumscribed capsules. Two cases had duodenal invasion; one of all cases had cul
      de sac metastasis. Compared with 12 non-aggressive tumors, the aggressive cases
      had larger tumor size (more than 9 cm) with a thicker capsule (more than 2 mm).
      In studies to investigate the prognostic index using nucleolar organizing region
      (NOR), proliferating cell nuclear antigen (PCNA) and flow cytometry as well as
      nuclear grade and mitotic index, we could not find the useful parameter to detect
      the malignant potential of PCTP. In the flow cytometric analysis of cellular DNA
      contents, two invasive cases and the only one case of the male patient among the
      non-aggressive group were aneuploid. In conclusion, although it is hard to
      predict the prognosis by microscopic findings only, those with a thick capsule
      and aneuploidy tend to be related to malignant potential.

PMID- 8750061
TI  - Light microscopic and electron microscopic features of cyclosporine
      nephrotoxicity in rats.
AB  - In order to clarify morphologic changes associated with cyclosporine (CS)
      nephrotoxicity, CS in ethyl alcohol at 25 mg/kg/day i.p. was administered to male
      Sprague-Dawley rats for periods of 1 to 8 weeks. Mean systolic BP was slightly
      increased in the CS group at 4 weeks (p < 0.05), but there was no difference
      compared to a control group at 8 weeks. Blood urea nitrogen was significantly
      elevated at 4 weeks and continued to rise (p < 0.005), whereas serum creatinine
      was elevated at 8 weeks. Microscopic examination of the kidneys from CS-treated
      rats at one week revealed cytoplasmic vacuolization in all segments of the
      proximal tubules, tubular inclusion bodies, and peritubular capillary congestion.
      Ultrastructurally, some vacuoles were neutral fat droplets, while others appeared
      as single membrane-bound structures due to dilatation of the endoplasmic
      reticulum. The tubular inclusion bodies were enlarged autolysosomes filled with
      distorted mitochondrial fragments. At two weeks, tubular regeneration was
      prominent, in addition to the above mentioned toxic tubulopathy. At four weeks,
      focal areas of interstitial fibrosis and tubular atrophy associated with cystic
      dilatation were seen. At 8 weeks, interstitial and intratubular
      microcalcification were present, in addition to patchy foci of interstitial
      fibrosis, but vascular lesions were not demonstrated. Although renal tubular
      changes characterized by vacuolization, inclusion bodies, and microcalcification
      and interstitial fibrosis are not specific for CS toxicity, these changes are
      commonly found in both humans and rats at high doses of CS.

PMID- 8750062
TI  - Expression of p53 protein, PCNA, and Ki-67 in osteosarcomas of bone.
AB  - Expressions of p53 protein, a product of the tumor suppressor gene were studied
      in osteosarcomas relating to various prognostic factors. Thirty-four
      osteosarcomas were investigated immunohistochemically with a monoclonal antibody
      clone PAb240, which recognizes a common conformational epitope of mutant p53
      proteins and another clone PAb1801, which reacts with both wild- and mutant-type
      p53 proteins. The results were compared with expressions of proliferating cell
      nuclear antigen (PCNA) and Ki-67 providing a simple method for the assessment of
      growth fractions of tumors. PAb240 stained nuclei and cytoplasm of tumor cells in
      8 of 34 osteosarcomas (23.5%), whereas PAb1801 reacted in all 34 osteosarcomas
      (100%). Fifteen tumors (44.1%) showed positivity for PAb1801 in more than half of
      the tumor cells. Twelve patients were alive and thirteen were dead. Tumors from 9
      patients (75%) who survived revealed only focal positive immunoreactions with
      PAb1801 and tumors from 6 patients (46.1%) who died revealed diffuse reactions.
      Twelve cases (35.3%) showed a high PCNA index (> 40%) and fibroblastic
      osteosarcomas revealed the highest PCNA positivity. Twenty-two cases (64.7%)
      revealed a very low Ki-67 index (less than 10%) and Ki-67 index showed a good
      correlation with PCNA positivity (r = 0.6247). Expressions of both wild-and
      mutant-type p53 protein, PCNA, and Ki-67 were not correlated with other clinical
      or pathological parameters.

PMID- 8750063
TI  - Availability of discographic computed tomography in automated percutaneous lumbar
      discectomy.
AB  - Automated percutaneous lumbar discectomy (APLD) has been developed since 1984
      when Gary Onik first attempted it. This procedure has many advantages and has
      been used widely in the treatment of protruded disc diseases. The success rate of
      APLD by authors from March 1988 to February 1993 when the discographic computed
      tomography (CT) had not been performed was 74%. In evaluating lumbar disc
      diseases, we have used discographic CT. According to the patterns of dye
      distribution in the disc, two different types of protrusion can be distinguished:
      broad dye base protrusion and narrow dye base protrusion. From April 1993 to July
      1994, 52 patients with protruded disc diseases were performed discographic CT. 23
      Patients had narrow dye base protrusion and 29 patients had broad dye base
      protrusion. 29 patients with a broad dye base on discographic CT were treated
      with APLD and evaluated. The success rate in these patients was 93% by Macnab's
      criteria. Thus, we suggest that it is mandatory to apply discographic CT to
      increase the success rate of APLD in patients with protruded disc diseases.

PMID- 8750064
TI  - Relationship between tissue plasminogen activator, plasminogen activator
      inhibitor and CT image in chronic subdural hematoma.
AB  - The present study was performed to investigate the relationship between the
      concentrations of tissue-type plasminogen activator (t-PA) and plasminogen
      activator inhibitor (PAI) and the CT images in 23 cases of chronic subdural
      hematomas (SDHs). The concentrations of t-PA and PAI-1 were quantified by enzyme
      linked immunosorbent assay (ELISA). Chronic SDHs were divided into five groups
      according to their appearance on computed tomography: high-density (n = 4),
      isodensity (n = 8), low-density (n = 5), mixed-density (n = 3), layering (n = 3)
      types. The volume of hematoma was measured with an image analyzing software
      program. The concentrations of t-PA were higher in layering (41.2 +/- 0.3 ng/ml,
      mean +/- standard error of the mean) and high-density (40.0 +/- 1.1 ng/ml) types
      compared to those of low-density (23.3 +/- 4.1 ng/ml) and iso-density (25.1 +/-
      3.7 ng/ml) types. The concentrations of PAI-1 were lower in layering (95.9 +/-
      1.0 ng/ml) and high-density (103.4 +/- 34.5 ng/ml) types compared to that of low
      density (192.5 +/- 2.6 ng/ml) type. So the ratio between t-PA and PAI-1 (t
      PA/PAI) was greater in layering and high-density types. The volume of hematoma
      was larger in mixed-density and layering types but statistically insignificant.
      These results presumably suggest that the ratio between t-PA and PAI
      concentration may contribute to the pathogenesis of the chronic SDH.

PMID- 8750065
TI  - Gamma knife radiosurgery for malignant tumors.
AB  - Between May 1990, and June 1994, 79 patients with malignant tumors were treated
      radiosurgically using a Leksell gamma unit at Asan Medical Center. Of these
      patients, 57 were metastatic brain tumor, 12 were glioblastoma multiforme (GM), 4
      were primitive neuroectodermal tumor, 3 were malignant germ cell tumor, 2 were
      recurrent lymphoma, and 1 was adenoid cystic carcinoma of the orbit. Among 57
      patients with metastatic tumors, 28 patients harboring 60 tumors were followed
      clinically and radiographically. The median marginal dose for these tumors was 30
      Gy and the median survival rate was 15 months. Twenty-one tumors disappeared and
      32 tumors decreased in size during 2 to 6 months after radiosurgery on computed
      tomographic or magnetic resonance imaging scans. All 12 patients with GM were
      treated with conventional radiation (6,240 approximately 6,500 cGy) after
      surgical resection or biopsy prior to radiosurgery (13 approximately 15 Gy to
      margin). The results were varied. Radiosurgical treatment of two recurrent
      lymphomas and three recurrent mixed germ cell tumors after radiation and
      chemotherapy provided rapid clinical improvement with disappearance of the tumor.
      However, new lesions appeared in two lymphomas and one mixed germ cell tumor
      within 3 to 4 months. One patient with adenoid cystic carcinoma of the orbit, who
      was treated radiosurgically prior to resection, is alive without recurrence 31
      months after the treatment. Gamma knife radiosurgery appears to be the best
      alternative method to surgical excision plus radiation therapy for single and
      multiple cerebral metastases. It also provides rapid palliation of symptoms due
      to recurrent malignant tumors. And it may have an adjuvant role in the treatment
      of some tumors delaying local recurrence, if given prior to resection. However,
      the preliminary results for the malignant gliomas were inconclusive.

PMID- 8750066
TI  - Cerebral venous thrombosis associated with maxillary and ethmoid sinusitis--a
      case report.
AB  - We herein report a young patient with cerebral venous thrombosis (CVT) with
      clinical and neuroradiological findings of the left maxillary and anterior
      ethmoid sinusitis. Serial brain MRIs showed cerebral venous infarct and
      thrombosis in the superior sagittal sinus (SSS). MR angiography demonstrated
      nonvisualization of SSS and bilateral transverse sinus. According to our
      knowledge, CVT associated with maxillary and ethmoid sinusitis has been reported
      very rarely. High index of suspicion and neuroimaging studies, especially brain
      MRI, and conventional or MR angiography are very important for the early
      diagnosis of CVT.

PMID- 8750067
TI  - Surgical video systems.
AB  - Surgical video systems (SVSs), which typically consist of a video camera attached
      to an optical endoscope, a video processor, a light source, and a video monitor,
      are now being used to perform a significant number of minimally invasive surgical
      procedures. SVSs offer several advantages (e.g., multiple viewer visualization of
      the surgical site, increased clinician comfort) over nonvideo systems and have
      increased the practicality and convenience of minimally invasive surgery (MIS).
      Currently, SVSs are used by hospitals in their general, obstetric/gynecologic,
      orthopedic, thoracic, and urologic procedures, as well as in other specialties
      for which MIS is feasible. In this study, we evaluated 19 SVSs from 10
      manufacturers, focusing on their use in laparoscopic applications in general
      surgery. We based our ratings on the usefulness of each system's video
      performance and features in helping clinicians provide safe and efficacious
      laparoscopic surgery. We rated 18 of the systems Acceptable because of their
      overall good performance and features. We rated 1 system Conditionally Acceptable
      because, compared with the other evaluated systems, this SVS presents a greater
      risk of thermal injury resulting from excessive heating at the distal tip of the
      laparoscope. Readers should be aware that our test results, conclusions, and
      ratings apply only to the specific systems and components tested in this
      Evaluation. In addition, although our discussion focuses on the laparoscopic
      application of SVSs, much of the information in this study also applies to other
      MIS applications, and the evaluated devices can be used in a variety of surgical
      procedures. To help hospitals gain the perspectives necessary to assess the
      appropriateness of specific SVSs to ensure that the needs of their patients, as
      well as the expectations of their clinicians, will be satisfied, we have included
      a Selection and Purchasing Guide that can be used as a supplement to our
      Evaluation findings. We have also included a Glossary of relevant terminology and
      the supplementary article, "Fiberoptic Illumination Systems and the Risk of Burns
      or Fire during Endoscopic Procedures," which addresses a safety concern with the
      use of these devices. While we made every effort to present the most current
      information, readers should recognize that this is a rapidly evolving technology,
      and developments occurring after our study was complete may not be reflected in
      the text. For additional information on topics related to this study, refer to
      the following Health Devices articles: (1) our Guidance Article, "Surgical Video
      Systems Used in Laparoscopy," 24(1), January 1995, which serves as an
      introduction to SVS terminology and includes a discussion of the significance of
      many SVS specifications; (2) our Evaluation, "Video Colonoscope Systems," 23(5),
      May 1994, which includes a detailed overview of video endoscopic applications and
      technology; and (3) our Evaluations of laparoscopic insufflators (21[5], May
      1992, and 24[7], July 1995), which address issues related to the creation of a
      viewing and working space inside the peritoneal cavity to facilitate
      visualization in laparoscopic procedures.

PMID- 8750069
TI  - Modified testing procedure for manual resuscitators to minimize the risk of
      barotrauma resulting from a malfunctioning exhalation valve.

PMID- 8750068
TI  - Shattering of glass injector vials in Abbott syringe systems.

PMID- 8750070
TI  - Western Medica oxygen regulator yokes incompatible with cylinder post valves.

PMID- 8750071
TI  - Use of pressure infusion with level 1 technologies L-10 gas eliminators and
      HotLine fluid warmers.

PMID- 8750072
TI  - The Draw-a-Person task in persons with mental retardation: what does it measure?
AB  - As a widely used, easy-to-administer, and nonthreatening task, the Draw-a-Person
      (DAP) holds particular promise as a nonverbal index of intelligence in persons
      with mental retardation. The DAPs of 108 adolescents and adults with mental
      retardation were reliably scored using Naglieri's cognitive and emotional
      disturbance scoring systems. Contrary to expectations, visual-motor skills
      emerged as the best predictor of DAP cognitive scores. Intelligence was
      correlated with DAP scores, but had considerably less predictive value than
      visual-motor skills. DAP emotional indicator scores were only modestly associated
      with social adaptation; even less support was found linking DAP emotional
      indicators to psychopathology. Findings point to considerable caution in using
      the DAP as an index of intelligence or as a screen for adjustment problems or
      specific psychopathology. Although related to intelligence, this popular task
      seems predominantly to measure visual-motor development in adults with mental
      retardation.

PMID- 8750073
TI  - Social skills and the stability of social relationships between individuals with
      intellectual disabilities and other community members.
AB  - Stability of social relationships may be an important indicator of lifestyle
      quality. Fifteen individuals with intellectual disabilities participated in an
      analysis of the relationship between their social skills (as measured via the
      Scales of Independent Behavior and the Assessment of Social Competence) and the
      stability of the social relationships they experienced with other community
      members, who were neither paid staff nor family members, across the course of 94
      consecutive weeks. A participant's social skills did a moderately good job of
      predicting the average social stability achieved by all of his or her social
      network members, but a poorer job of predicting the average social stability
      achieved by the participant's three most stable social network members. The
      findings suggest that the stability of a participant's most stable social network
      members is based not on the participant's social skills, but rather on other
      factors.

PMID- 8750074
TI  - Parent- and self-ratings of anxiety in children with mental retardation:
      agreement levels and test-retest reliability.
AB  - This study examined fears in children with and without developmental
      disabilities. Children assigned to classes designed as developmentally
      handicapped (D), integrated (or mainstreamed) (I), and regular (R) were assessed.
      In all, 82 children were tested and retested over a 2-week interval. Self ratings
      and parent ratings were obtained. Three instruments were used to assess specific
      fears, social anxiety, social competence, and behavior problems: the Fear Survey
      Schedule for Children--Revised, the Social Anxiety Scale for Children, and the
      Child Behavior Rating Form. Correlations between parent and child ratings were
      fair to good. Child-parent agreement was nonsignificantly higher for children
      without disabilities and for children with mild handicaps integrated into regular
      education programs than for children in classes designated as Developmentally
      Handicapped. Children's test-retest reliabilities were generally higher than
      those of parents. Children without disabilities showed significantly higher
      consistency over time than children with disabilities.

PMID- 8750075
TI  - The Nisonger CBRF: a child behavior rating form for children with developmental
      disabilities.
AB  - Although the rate of behavior and emotional problems of children with mental
      retardation is considerably higher than the rate among typically developing
      children, there is a shortage of tools for assessing persons with mental
      retardation. The Child Behavior Rating Form (CBRF) was modified by altering
      instructions and adding new items describing behavior problems known to occur in
      children with mental retardation. The adapted scale was named the Nisonger CBRF.
      Three hundred sixty-nine children being assessed at a University Affiliated
      Program for MR/DD were rated on the CBRF by their parents and teachers.
      Independent factor analyses of parent and teacher ratings produced two Social
      Competence subscales and six Problem Behavior subscales. These results were
      largely consistent across rater types and similar to prior findings with the
      CBRF. Internal consistency was generally high, parent-teacher agreement was
      satisfactory, and subscales from the Nisonger CBRF correlated highly with
      analogous subscales from the Aberrant Behavior Checklist. The Nisonger CBRF
      appears to be a promising new tool for assessing behavioral and emotional
      problems in children with mental retardation; however, further psychometric work
      is warranted.

PMID- 8750076
TI  - The Nisonger Child Behavior Rating Form: age and gender effects and norms.
AB  - The Nisonger CBRF is a new informant behavior rating scale that was adapted for
      assessing children and adolescents with mental retardation. A total of 369
      children referred to interdisciplinary diagnostic clinics for children with
      developmental disabilities were rated on the Nisonger Child Behavior Rating Form
      by their parents and teachers. Normative data (means, T scores, and percentiles)
      are presented Subscale scores were analyzed as a function of age and gender. Age
      influenced 3 of 8 subscales on the parent ratings and 1 subscale on the teacher
      ratings. Gender did not influence subscale scores. Age and gender results are
      discussed in relation to previous studies of subject variables.

PMID- 8750077
TI  - Current limits to reinforcer identification for some persons with profound
      multiple disabilities.
AB  - Fifteen persons with profound mental retardation were divided into two groups.
      One group was identified with chronic training needs by habilitative staff and
      the other group served as a control. In an attempt to identify a reinforcer, each
      participant received a preference assessment and a simple, low-effort treatment
      procedure. In Experiment 1, only individuals who approached at least one stimulus
      on 80% or more of the preference assessment trials ("high preference") showed
      reinforcement effects in treatment. However, three individuals showing high
      preference failed to show treatment effects. All persons identified with chronic
      training needs failed to show reinforcement effects. Experiment 2 analyzed
      characteristics of the two groups and found significant differences in overall
      movement and response latency. Limitations of the current reinforcement
      technology were apparent for identifying reinforcers in the group with chronic
      training problems. Research is suggested for evaluating training alternatives for
      people with profound multiple disabilities who move very little or who respond
      with very long latencies.

PMID- 8750078
TI  - An air-puff stimulus method for elicitation of ultrasonic vocalizations in rats.
AB  - Rat 22 kHz ultrasonic vocalizations (USVs) are thought to reflect an aversive
      behavioral state, perhaps a type of anxiety or fear, and have proven useful in
      the study of the neural mechanisms of these states. This paper describes a simple
      procedure for presentation of an aversive but non-painful air-puff stimulus for
      the elicitation of USVs from rats. When directed at the rat's dorsal or
      dorsolateral head and neck region, this stimulus reliably elicits ultrasonic
      vocalizations from nearly all rats tested and as such represents a valuable
      alternative to other stimuli such as aggressive encounters, electric shock, or
      acoustic startle. The USV response may attenuate with repeated testing, yet
      remains readily inducible and is therefore suitable for studies involving
      habituation. The materials for generating this stimulus and the accompanying
      testing procedure comprise an efficient method with which this aversively
      motivated rodent behavior can be examined. The potential utility of this
      technique in studies of aversively motivated behaviors and its relevance to
      studies of startle responding is discussed.

PMID- 8750079
TI  - A flexible PC-based physiological monitor for animal experiments.
AB  - We have developed a flexible physiological monitoring and analysis system for
      physiological studies in which data are obtained over extended periods. Our
      system uses low-cost personal computer hardware to concentrate data from existing
      multiple monitoring devices. All monitored parameters are displayed on a single
      screen and recorded in a single file. The system automates the process of
      physiological record keeping by providing continuous displays of vital signs. In
      addition, audible and visual alarms are produced when vital signs are outside of
      acceptable ranges, prompting the experimenter to take corrective actions. The
      central element of the system is a program running in a dedicated manner on an
      IBM PC-compatible computer. The program is written in the C language and makes
      use of a graphics library to display traces and analysis results in real time on
      any standard display for the PC. This program assigns the analog channels of an
      A/D board to particular physiological parameters by initially reading a
      configuration file, which also describes the alarm conditions and analysis
      routine for each parameter. All hardware specific code is isolated into well
      defined modules. The program is both highly flexible with regard to different
      sets of parameters and highly portable for different experimental and computer
      environments.

PMID- 8750080
TI  - Quantitative measurement of muscle strength in the mouse.
AB  - We have designed a special dynamometer for measuring mouse forelimb muscle
      strength and endurance. The device exploits a mouse's tendency to grasp a
      horizontal metal bar while suspended by its tail. A threshold value for the
      magnitude and duration of force that the mouse can exert is obtained by first
      allowing the animal to grasp the bar and then applying a steadily increasing
      downward force to the opposite end of a cable to which the mouse attaches. The
      bar is attached to a force transducer and pen recorder to produce a permanent
      record of the force produced by the mouse. Test results show that this
      dynamometer provides quantitative measurements of muscle strength and endurance
      in the mouse. Comparisons between experimental groups of normal and wobbler mice,
      a model for lower motor neuron disease, show that both the force exerted by the
      animals (muscle strength), and the duration of the pull (endurance), can be
      quantified and statistically analyzed. This technique can be used as an assay for
      quantitating the effects of in vivo drug treatments on murine neuromuscular
      disorders.

PMID- 8750081
TI  - A phase plane representation of rat exploratory behavior.
AB  - Rat spontaneous spatial behavior is considered to be stochastic and is therefore
      commonly analyzed in terms of cumulative measures. Here, we suggest a method
      which generates a moment-to-moment representation of this behavior. It has been
      proposed earlier that rat spatial behavior can be partitioned into natural units
      termed excursions (round trips) performed from a reference place termed the rat's
      home base. We offer a phase plane representation of excursions (plotting the
      rat's momentary location against its momentary velocity). The results reveal a
      geometrical pattern, typical of young age and early exposure. It consists of low
      velocity and intermittent progression while moving away from the home base
      (upstream segment), and high velocity while moving back to it (downstream
      segment). The asymmetry between the two segments defines a field of significance
      in the rat's operational world. This field undergoes regular transformations,
      revealing thereby the rat's strategy of occupancy of the environment. The
      presented dynamics could provide a framework for the interpretation of concurrent
      neural events associated with navigation and spatial memory.

PMID- 8750082
TI  - A digital feedback controller application for studying photoreceptor adaptation
      by 'voltage clamp by light'.
AB  - We present a new digital feedback application for the study of the sensitivity
      characteristics of photoreceptors. The amplitude of the recorded membrane voltage
      of a cell is steered by changing the incoming light intensity with a motor-driven
      circular, linear neutral-density wedge (CFW). The voltage response is sampled and
      fed to a software position controller of the CFW. The controller determines the
      position of the wedge according to the desired (command) value of the response.
      The light intensity changes during steady-state represent the sensitivity change,
      the time-course of adaptation.

PMID- 8750083
TI  - Determination of tetrahydro-beta-carbolines in rat brain by gas chromatography
      negative-ion chemical ionization mass spectrometry without interference from
      artifactual formation.
AB  - This paper describes a quantitative method for neuroactive alkaloids, 1-methyl
      1,2,3,4-tetrahydro-beta-carboline (MTBC) and 1,2,3,4-tetrahydro-beta-carboline
      (TBC), in rat brain by gas chromatography-negative-ion chemical ionization mass
      spectrometry (GC-NICIMS). After addition of tetradeuterated MTBC and TBC
      (internal standards), the samples were subjected to deproteinization, reaction
      with fluorescamine, solvent extractions, trifluoroacetylation and GC-NICIMS
      analysis. In contrast to the other previous methods, the artifactual formation
      during analysis did not interfere with the determination of MTBC and TBC because
      their precursor tryptamine was removed as a fluorescamine derivative from the
      analytical system at the first step of pretreatment. MTBC and TBC were
      specifically and reliably determined in the range of pg-ng/sample. Application of
      the proposed method has revealed that the MTBC and TBC contents in rat brain
      significantly increase after intraperitoneal administration of MTBC and TBC,
      indicating their ability to easily cross the blood-brain barrier.

PMID- 8750084
TI  - The spinal loop dialysis catheter: characterization of use in the unanesthetized
      rat.
AB  - To permit long-term measurement of time-dependent changes in levels of dialyzable
      drugs and transmitters in the spinal intrathecal (i.t.) space of the
      unanesthetized rat, we developed a dialysis catheter for chronic placement. This
      was accomplished by constructing a loop probe 9 cm in length from 0.3-mm-diameter
      dialysis tubing that was made impermeable except for the distal loop. This loop
      catheter was readily inserted though an incision in the cisternal membrane and
      passed to the lumbar enlargement. The ends of the catheter were then externalized
      on the top of the head. To permit i.t. injections, an additional i.t. catheter
      could also be inserted simultaneously by the same route. For dialysis, an
      external end of the loop catheter was connected to a syringe pump and perfused
      with artificial CSF (10 microliters/min) and the out flow collected. A series of
      studies were performed to demonstrate the characteristics and utility of this
      technique. (1) Stability of resting release: glutamate and glucose concentrations
      in spinal dialysate showed no significant changes from 3 to 10 days after
      implantation. (2) Spinal cord ischemia: ischemia induced by aortic occlusion or
      cardiac arrest evoked a time dependent increase in retrieved glutamate. (3)
      Spinal cord compression caused a time-dependent glutamate, aspartate and PGE2
      increase. (4) Noxious afferent stimulation induced by the injection of formalin
      into the hindpaw resulted in a rapid and transient increase in dialysate
      glutamate concentration. (5) Direct activation of spinal excitatory amino acids
      receptors by i.t. injection of kainic acid (1 microgram) evoked a significant
      increase in aspartate and taurine. (6) Continuous delivery of spinal opiate
      (alfentanil) via dialysis resulted in a maintained, concentration dependent
      elevation in the thermal escape latencies in the unanesthetized rat. The loop
      dialysis catheter provides a robust experimental tool for studying time dependent
      changes in the concentration of diffusible substances in spinal CSF over an
      extended post-implantation interval and allows comparison of these changes with
      concurrently assessed behavioral indices.

PMID- 8750085
TI  - Preservation of the structural integrity of a freshly lesioned or transplanted
      mouse neocortex and the immunoreactivity of cell-specific marker proteins in
      demineralized histological material.
AB  - Analysis of superficially lesioned or grafted brains poses the problem that their
      removal from the skull prior to histological processing often causes damage to
      the operated area and may lead to loss of the graft. Here, we propose an original
      approach to this problem, developed on mice whose cortices have been surgically
      lesioned and some grafted with fetal neural tissue. The experimental animals were
      killed 1, 3 or 6 days after operation. Our procedure was based on the softening
      of skulls by demineralization in Gendre's picric solution, followed by
      solidification of the wounded region by embedding in polyester wax. This
      permitted the preparation of serial sections from brains together with
      neurocrania. To check their immunoreactivity, the sections were later reacted
      with specific antisera for glial fibrillary acidic protein (GFAP), microtubule
      associated protein 2 (MAP2), calbindin, and the thermolabile cell-surface
      glycoprotein Thy-1. The histological material revealed excellent structural
      integrity and cytoarchitecture. In transplanted animals, the tiny graft,
      protected by the overlying bone, was found in the host cavity. Immunostaining
      showed typical localization of the chosen marker proteins. The anti-Thy-1
      antibody enabled us to distinguish between graft and host tissues, which
      differed, in our experiments, in their expression of two distinct allelic forms
      of the Thy-1 molecule. The method lends itself perfectly to histochemical study
      of the earliest stages of freshly operated superficial brain regions in small
      laboratory animals, and should also be applicable to the evaluation of other
      brain structures which are difficult to gain access to without being damaged.

PMID- 8750086
TI  - Loss of frequencies in autocorrelations and a procedure to recover them.
AB  - We show that the standard methods, like the autocorrelation of a discrete time
      series, such as a spike train, can often miss prominent oscillation frequencies.
      In particular, if a phenomenon involves bursting and oscillations at two or more
      frequencies, the higher frequencies, with a lesser number of spikes per burst,
      can be often missed by the conventional methods. It is argued that on should
      separate the intraburst phenomena from the interburst phenomena by identifying
      bursts as single events. The distribution of oscillation frequencies should then
      computed by evaluating the autocorrelation of these events. A method is also
      developed for situations where intraburst and interburst time scales overlap
      significantly. It is shown that the correct estimate of strengths of various
      frequencies is found by using different thresholds for burst identification. The
      method is applied to data from a neuron in the subthalamic nucleus of a
      Parkinsonian (MPTP-treated) monkey. The conventional analysis shows that the
      neuron oscillates at only 6 Hz, whereas the new analysis reveals the presence of
      an additional, predominant, oscillation frequency of 18 Hz.

PMID- 8750087
TI  - 3-dimensional morphometry of intact dendritic spines observed in thick sections
      using an electron microscope.
AB  - An experimental technique is described which allows observation of fixed neuronal
      dendrites at magnifications from 10-12 K. The method uses 4-7-microns-thick
      sections of Epon-embedded tissue with nerve cells that are first impregnated by
      the rapid Golgi technique and then stained with gold particles/aggregates using a
      modified gold-toning procedure. A relatively high acceleration voltage (200 kV)
      is employed to observe in fine detail the dendritic fragments of interest at
      different angular positions in space, by using a eucentric goniometer stage with
      a tilt angle of +/- 45 degrees. Image analysis methodology is proposed which
      permits estimation of 3-dimensional (3D) lengths and of the volume of observed
      intact dendritic spines. The advantages of the technique with respect to 3D
      reconstruction methodology are discussed.

PMID- 8750088
TI  - Three-dimensional reconstruction and surface rendering of the five different
      spectral types of cone pedicle in the turtle retina.
AB  - Pseudo-3-dimensional models and surface renderings of a small group of
      neighboring cone pedicles in the turtle retina, in which the 5 different spectral
      types are represented, have been made from scanned serial electron micrographs
      using a Macintosh personal computer, Autocad and Studio Pro software. The
      resultant computer generated images clarify the morphological differences between
      the spectral types and show how they are related to each other via telodendrial
      connections and different levels of ending in the neuropil of the outer plexiform
      layer (OPL). The double cone pedicles end highest in the neuropil and the single
      red and green pedicles lie slightly lower into the OPL with the single blue and
      ultraviolent (UV)-sensitive cone pedicles coming in from obliquely angled axons
      to assume positions between the others much more vitread in the OPL. Telodendria
      interconnect the double and single red and green cones but not the blue and UV
      sensitive cones.

PMID- 8750089
TI  - Laser exposure of Parylene-C insulated microelectrodes.
AB  - The polymer, Parylene-C, has proven to be a biocompatible insulation for
      microelectrodes. However, due to its inert nature, the removal of the insulation
      from the tips of microelectrodes is difficult. This paper describes the use of an
      ultraviolet laser system to micromachine Parylene-C insulation with photoablation
      to precisely expose an arbitrary shape recording or stimulating surface.

PMID- 8750090
TI  - Spike-train acquisition, analysis and real-time experimental control using a
      graphical programming language (LabView).
AB  - A solution is described for the acquisition on a personal computer of standard
      pulses derived from neuronal discharge, measurement of neuronal discharge times,
      real-time control of stimulus delivery based on specified inter-pulse interval
      conditions in the neuronal spike train, and on-line display and analysis of the
      experimental data. The hardware consisted of an Apple Macintosh IIci computer and
      a plug-in card (National Instruments NB-MIO16) that supports A/D, D/A, digital
      I/O and timer functions. The software was written in the object-oriented
      graphical programming language LabView. Essential elements of the source code of
      the LabView program are presented and explained. The use of the system is
      demonstrated in an experiment in which the reflex responses to muscle stretch are
      assessed for a single motor unit in the human masseter muscle.

PMID- 8750091
TI  - The twitch interpolation technique for study of fatigue of human quadriceps
      muscle.
AB  - The aim of the study was to examine if the twitch interpolation technique could
      be used to objectively measure fatigue in the quadriceps muscle in subjects
      performing submaximally. The 'true' maximum isometric quadriceps torque was
      determined in 21 healthy subject using the twitch interpolation technique. Then
      an endurance test was performed in which the subjects made repeated isometric
      contractions at 50% of the 'true' maximum torque for 4 s, separated by 6 s rest
      periods. During the test, the force response to single electrical stimulation
      (twitch amplitude) was measured at 50% and 25% of the estimated maximum torque.
      In 10 subjects, the test was repeated 2-4 weeks later. Twitch amplitudes at 50%
      of maximum torque declined exponentially with time in 20 of 21 subjects. The
      distribution of the exponential rate constant was skewed with a mean of 4.6 h-1
      and range of 0.3-21.5 h-1. After logarithmical transformation, the distribution
      of the exponential rate constant fitted closely to a normal distribution, and the
      inter-individual variation was SD = 1.15 compared to an intra-individual
      variation of 0.29. The coefficient of correlation for repeated determination was
      0.91 (P < 0.001, n = 10). In conclusion, the twitch technique can be used for
      objectively measuring fatigue of the quadriceps muscle.

PMID- 8750092
TI  - Investigation of the factors necessary for growth of hippocampal neurons in a
      defined system.
AB  - We have developed an in vitro system that combines the use of a defined medium
      with a chemically defined surface for the differentiation of embryonic rat
      hippocampal neurons. Cells were grown on silica substrates modified with two
      chemically distinct molecules: poly-D-lysine and an amine-containing
      organosilane. Cells were dissociated by mechanical or enzymatic methods and grown
      in serum-containing versus serum-free medium on these surfaces. Our results
      demonstrate that optimal survival and growth in serum-free medium occurs on the
      artificial surfaces. X-ray photoelectron spectroscopy (XPS) was used to analyze
      the surfaces both before and after cell cultures. In addition, surface properties
      such as elemental composition, the initial thickness of the substrate material,
      and the thickness of material deposited during the course of cell culture were
      quantified after cell removal. Taken together, the results from the cell culture
      and surface analysis demonstrate that the media, proteins deposited from the
      media onto the surface, surface composition, and properties intrinsic to neuronal
      membranes all interact in a complex fashion to determine whether or not the cells
      will adhere and survive in culture. In particular, the role of material deposited
      from the medium onto the culture substratum may be more important than have been
      previously appreciated. This system allow for the study of neuronal
      differentiation in a well-defined environment.

PMID- 8750093
TI  - Cuprolinic blue (quinolinic phthalocyanine) counterstaining of enteric neurons
      for peroxidase immunocytochemistry.
AB  - This report details a method for the use of Cuprolinic Blue (quinolinic
      phthalocyanine) as a counterstain for immunoperoxidase Phaseolus vulgaris (PHA-L)
      labeled fibers in gastrointestinal wholemounts. Cuprolinic Blue (in the presence
      of high MgCl2 concentration) forms a particularly stable blue chromophore with
      single-stranded RNA in neuronal Nissl substance and nucleoli. In contrast to the
      non-specific staining provided by traditional neuronal dyes. Cuprolinic Blue
      produces prominent enteric neuron staining with minimal coloration of the muscle
      and connective tissue surrounding the ENS plexuses. However, this specific
      staining pattern is not obtained when the dye is used as a neuronal counterstain
      for immunoperoxidase-labeled material unless it is applied before the DAB
      chromagen. The counterstaining of gut wholemounts is optimized by using 0.5%
      Cuprolinic Blue at 37 degrees C. A lower concentration of the dye and temperature
      is useful for the concomitant delineation of the PHA-L immunoperoxidase-labeled
      injection sites in brainstem sections. The protocols outlined for Cuprolinic Blue
      counterstaining of both enteric and central nervous system material are also
      appropriate for the localization of other immunocytochemically identified
      antigens.

PMID- 8750094
TI  - Adapters for combined intrapipette pressure pulses and patch pipette step
      movements during 'blind' cell search in brain slices.
AB  - A procedure is described for 'blind' cell search in brain slices based on
      pressure pulses instead of steady-state pressure applied to the patch pipette
      during its stepwise movements. For reproducibility of the pressure/movement
      pattern during the cell search, we have developed two adapters, one for
      electrically and the other for hydraulically driven micromanipulators which
      generate pressure pulses synchronized with patch-pipette step movements. Both
      adapters increase the intrapipette pressure prior to a step movement of the
      pipette, maintain the pressure during the pipette movement, and release it
      between steps, thus minimizing the possibility of 'blowing-away' the cells during
      the search. The hydraulic micromanipulator adapter converts this into a stepping
      one. Both adapters also allow simultaneous recording of pipette step movements
      and of intrapipette pressure. The use of these adapters allows standardization of
      the 'blind' cell search and greatly increases the success rate of cells
      detection.

PMID- 8750095
TI  - System for projection of a three-dimensional, moving virtual target for studies
      of eye-hand coordination.
AB  - Eye-hand tracking of moving visual objects in three-dimensional (3D) space is
      common in the behavioral repertoire of primates. However, behavioral and/or
      neurophysiological studies of this function are lacking mainly because devices do
      not exist that allow its investigation. We describe a device by which a spot of
      light can be presented in the immediate extrapersonal space of a subject and can
      be moved in various trajectories in 3D space. The target is a real image of a
      circular aperture produced by a system consisting of a light source, aperture,
      filters, several lenses and fold mirrors, and a large concave mirror to focus the
      final real image. Rapid, computer-controlled movement of the image is obtained by
      tilting a gimbal-mounted guide mirror (for x and y motion) and by translating a
      lens (for motion in the z direction). A second configuration of the system allows
      movement of a 3D image in the 3D space. Hand motion is monitored by means of a
      sonic, 3D, position-measurement system.

PMID- 8750096
TI  - Specific molecular mass detection of endogenously released neuropeptides using in
      vivo microdialysis/mass spectrometry.
AB  - The specific molecular detection of the endogenous neuropeptides methionine
      ([Met]5) enkephalin and neurotensin released in vivo in rat brain has been
      accomplished using microdialysis and mass spectrometry. Microdialysis probes were
      implanted in specific brain regions and were used to collect samples from brain
      extracellular fluids in unanesthetized, freely moving animals.
      Microelectrospray/tandem mass spectrometry was used to achieve molecular-specific
      identification of the neuropeptides with a sensitivity in the amol/microliters
      range. Measurements of the amounts of neuropeptides in the dialysates obtained
      from studies of KCl-stimulated release showed that [Met]5-enkephalin from the
      globus pallidus/ventral pallidum region was present at a level of approximately 4
      6 fmol/10 microliters of dialysate and neurotensin from the hypothalamus of
      approximately 500 amol in 10 microliters of dialysate. In this manuscript, we
      present the first data of a mass- and molecular-specific detection and
      quantitation of individual neuropeptides released in response to either
      intracerebrally or systemically administered compounds.

PMID- 8750097
TI  - The use of peroxidase substrate Vector VIP in electron microscopic single and
      double antigen localization.
AB  - Very few chromogens used in immunoperoxidase reactions can be combined to
      simultaneously localize two neural antigens with different labels at both light
      (LM) and electron (EM) microscopic levels. The objective of this study was to
      investigate the EM properties of a novel purple chromogen introduced by LM
      immunostaining by Vector Laboratories under the commercial name Vector VIP. The
      Vector VIP (VIP) was employed to demonstrate anterogradely transported Phaseolus
      vulgaris-leucoagglutinin (PHA-L), retrogradely transported cholera toxin subunit
      B (CTB) and acetylcholine synthesizing enzyme choline acetyltransferase (ChAT) in
      single and double antigen immunostaining in combination with the chromogen
      3,3'diaminobenzidine (DAB). The VIP reaction product proved resistant to loss
      during post-fixation in OSO4 and dehydration in acetone. In EM preparation, the
      VIP reaction product was granular in appearance and easily distinguishable from
      the diffuse reaction product of DAB. Compared to the chromogen benzidine
      dihydrochloride (BDHC), the VIP reaction procedure is much simpler, more
      sensitive and consistently generates the same texture of the electron-dense
      precipitate. This study demonstrates the usefulness of VIP as a chromogen for
      correlative LM and EM immunoperoxidase staining. The VIP can be used either in
      single or double immunostaining in combination with DAB. In addition, we have
      examined the EM properties of another commercial chromogen, peroxidase substrate
      Vector SG (SG). The blue-gray reaction product of this chromogen is strongly
      osmiophilic and the electron-dense precipitate appears amorphous.

PMID- 8750098
TI  - Hyperosmotic activation of transmitter release from presynaptic terminals onto
      retinal ganglion cells.
AB  - A method for evoking neurotransmitter release without light stimulation has been
      developed and applied to a retinal slice preparation of the tiger salamander
      (Ambystoma Tigrum). This method utilizes a micropipette containing hyperosmotic
      levels of sucrose in Ringer, positioned within the inner plexiform layer (IPL)
      under visual control. Intermittent pressure (between 0.1 and 2 bars) applied to
      the pipette evoked release of neurotransmitters which were evaluated with whole
      cell recording (WCR) technique applied to cells in the ganglion cell layer.
      Pharmacological studies were used to characterize the properties of the
      hyperosmotic sucrose-evoked response (HSER) and in some cases, we compared the
      HSER with synaptic currents evoked by light stimulation. The HSER typically
      consisted of both inhibitory and excitatory components with a reversal potential
      in between that for chloride (approximately -60 mV) and non-specific cation
      channels (approximately 0 mV). Relatively pure inhibition or excitation could be
      revealed through pharmacological techniques by blocking the inhibition with
      picrotoxin/strychnine or by blocking the glutamatergic neurotransmission with D
      AP7 (D-2-amino-7-phosphonoheptanoate) and NBQX (2,3-dihydroxy-6-nitro-sulfamoyl 
      benzo (F) quinoxaline). A comparison of light-evoked responses (LER) and the HSER
      suggested that they activate the same pool of releasable neurotransmitter.

PMID- 8750099
TI  - A new methodological approach to the study of habituation: the use of positive
      and negative behavioral indices of habituation.
AB  - This report details a new method to measure habituation in an open-field. In
      addition to the measurement of spontaneous locomotor activity, time spent per
      visit to the center zone (CZ) is also measured. Critically, a small object is
      placed in the CZ to modulate an animal's investigatory response. When an animal
      is first exposed to the open-field, the presence of the object does not affect
      the duration of its visits to the CZ but, if the animal is given one additional
      10-min exposure to the open-field, then the presence of the object substantially
      increases the duration of its visits to the CZ. The presence of the object,
      however, has no effect on the rat's locomotor activity. Thus, habituation could
      be observed by two different measures: a decrease in locomotor activity and an
      increase in an animal's investigatory response to a stimulus object. A basic
      problem with a reliance solely upon a decrease in locomotor activity to measure
      habituation is that it represents a negative change in behavior. The present
      method circumvents this shortcoming by incorporating a positive behavioral
      measure of habituation in conjunction with the measurement of locomotor activity.
      This modification of the open-field test offers substantial utility for studies
      of neurotoxicology and memory because one can assess concurrently treatment
      effects on motor activity, attention to an object and memory.

PMID- 8750100
TI  - Sampling variation caused by A/D cards due to external trigger.
AB  - In electrophysiological recording, a microcomputer-based analog-to-digital (A/D)
      card is an indispensable instrument for signal acquisition and analysis. In our
      studies, evoked responses sampled by our A/D card showed variation among
      different cycles. If several cycles had been averaged, the resultant waveform
      would have a smaller peak amplitude and a longer duration. To explain this
      phenomenon, a simulated sampling model of compound action potential was proposed.
      Our experimental data agreed very well with the prediction of the simulated
      model. The long and varied delay time between the external trigger and the first
      sampling in each cycle by our A/D card might be the main cause of such variation.
      This problem could not be solved by any post-sampled programming. Hence, for
      those electrophysiological laboratories which sampled evoked responses, to buy a
      new A/D card might be the most straightforward solution to the problem.

PMID- 8750101
TI  - A novel, rapid flat-mounting technique for visualizing antibody labeling in the
      retina.
AB  - Complete analysis of retinal tissue is difficult because it consists of a thin
      neural tissue spread across the back of a hemispheric surface. Conventional
      sectioning in a plane parallel to a central axis of symmetry produces a large
      number of samples, each containing only a small amount of the tissue of interest.
      Consequently, quantitative comparison of any feature of interest typically uses a
      small fraction of the sections from each retina, because analysis of the entire
      collection of sections is too time consuming. Such a sampling process can lead to
      misleading or erroneous conclusions. We present a new method which allows
      complete analysis of the retina using a small number of samples produced by
      sectioning flattened retinas. This procedure is straightforward as illustrated
      using an antibody against proliferating cell nuclear antigen (PCNA) to locate
      dividing cells in the teleost fish retina. Immunocytochemical staining on flat
      sectioned retinas was quantified using a computer-based image analysis system.
      When the cells of interest are randomly distributed, conventional sampling
      procedures can seriously under- or over-estimate their number. The new technique
      presented allows significantly more efficient examination and quantification of
      the entire retina as compared to conventional techniques.

PMID- 8750102
TI  - Optical imaging of intracellular chloride in living brain slices.
AB  - We developed an optical imaging technique to measure changes in intracellular
      levels of Cl- in neurons within the living brain slice. After rat brain slices
      were incubated with the permeant form of the Cl(-)-sensitive dye, 6-methoxy-N
      ethylquinolinium chloride (MEQ), neurons could be imaged within the hippocampus,
      cerebral cortex and cerebellum using fluorescence microscopy. Both soma and
      dendrites were clearly visible in pyramidal neurons, interneurons, Purkinje cells
      and cerebellar granule cells. Increased intracellular levels of Cl- were produced
      by bath application of the inhibitory neurotransmitter, gamma-aminobutyric acid
      (GABA). Within hippocampal pyramidal neurons and interneurons, GABA produced a
      concentration-dependent decrease in fluorescence (EC50 = 200 microM). The GABA
      response was mediated via the GABA receptor since it was blocked by picrotoxin
      and mimicked by the agonist, muscimol. Muscimol, which is not transported by the
      GABA re-uptake pump, was approximately 20-fold more potent than GABA. The method
      developed was also used to image intracellular Cl- levels with UV laser scanning
      confocal microscopy. Even greater resolution was obtained and deeper structures
      could be imaged in cerebral cortex and hippocampus. This is the first
      demonstration of optical imaging to measure intracellular Cl- dynamics in living
      brain slices using fluorescence microscopy and laser scanning confocal
      microscopy.

PMID- 8750103
TI  - Microcomputer-based pulse stimulator.
AB  - A low-cost PC-based 2-channel stimulator was designed. This device can generate
      regular current pulses for many neuroscience experiments. It can also generate
      irregular pulses for nerve stimulation, thus could possibly avoid the problem of
      sensitization or habituation in the central nervous system. The stimulation
      frequency (can be < 0.0005 Hz) and pulse duration (5 microseconds to 65 ms) of
      this device can be programmed by an interactive user interface. Furthermore, the
      output current (0-10 mA) can be continuously varied and was optically isolated to
      minimize stimulus artifact. Moreover, features such as low-power consumption (0.2
      mA of a 9 V battery) and high-compliance output (> 120 V) could accommodate the
      stimulator for widespread applications. A trial of nerve stimulation was
      illustrated besides the electrical specifications of the stimulator.

PMID- 8750104
TI  - In vivo microdialysis and gas chromatography/mass spectrometry for studies on
      release of N-acetylaspartlyglutamate and N-acetylaspartate in rat brain
      hypothalamus.
AB  - Microdialysis and gas chromatography/mass spectrometry was used for the
      measurement of extracellular N-acetylaspartate (NAA) and N
      acetylaspartylglutamate (NAAG) in rat hypothalamus. The sensitivity of the method
      for each of these compounds was approximately 5 pmol/30 microliters of dialysate.
      Baseline NAA concentrations in dialysate were estimated to be approximately 25
      pmol/36 microliters, while that for NAAG was at or below the detection limit of 5
      pmol/ 36 microliters. In vivo and in vitro calibrations of microdialysis probes
      showed that the recovery for NAA was approximately 10 percent. For NAAG, the in
      vitro recovery was 6.3%, and in vivo recovery, 11%. Depolarization stimulation
      using 100 mM KCl in the microdialysis perfusate was employed to measure
      extracellular NAA and NAAG concentrations. Extracellular NAA was elevated to
      approximately 70 pmol/36 microliters dialysate following depolarization. No
      significant elevation of NAAG was observed. By infusing known amounts of stable
      isotopically labeled NAAG-d3 via the microdialysis probe and measuring the
      isotopically labeled catabolic product, NAA-d3, in collected microdialysate, we
      were able to confirm the existence of one or more hydrolytic enzymes active
      towards NAAG in the hypothalamus. This finding suggest the possible involvement
      of active metabolic processes in the relationship between NAAG and NAA releases.

PMID- 8750105
TI  - Preparation of carbon-fibre microelectrode for extracellular recording of
      synaptic potentials.
AB  - A method is proposed for rapid and effective forming of the recording tips of
      carbon-fibre microelectrodes by trimming and treating the tip with electric
      current pulses. The tip is trimmed to the required length. The signal-to-noise
      ratio of carbon-fibre microelectrodes is improved at low-frequency range (less
      than 100 Hz) after the treatment. The same microelectrode may be used for several
      experiments because of the possibility to trim and treat the tips repeatedly.
      This method also allows one to readily fabricate 2- or multi-channel carbon-fibre
      microelectrodes with the vertical distance between recording tips from few tens
      to hundreds of micrometres. As an example, the process of fabrication of a 2
      channel microelectrode is described.

PMID- 8750106
TI  - Generating a phage display antibody library against an identified neuron.
AB  - The generation of monoclonal antibodies by conventional hybridoma technology is
      limited by the diversity of the clones and the difficulties of screening the
      antibodies and of their large-scale production from isolated clones. As an
      alternative approach, we have investigated the suitability of phage display
      libraries for the production of recombinant antibodies against an identified
      neuron. Mice were immunized with isolated leech Retzius (R) neurons. The spleen
      poly A+ RNA was isolated and first-strand cDNA was prepared. The variable regions
      of light- and heavy-chain IgG molecules were amplified by the polymerase chain
      reaction (PCR) and separate libraries of each were constructed and combined in
      the pComb8 vector to yield a combinatorial library of approximately 10(7)
      transformants. Single R neurons that were plated in culture bound approximately
      100 phages on a first screen and several thousand when the first batch was re
      screened. Of these, 96 individual phage colonies were isolated and used for
      immunocytochemistry with leech CNS ganglia: 41 exhibited general staining, 20
      showed no detectable staining and 30 stained selective subsets of neurons
      including (but not specific for) the R neuron. The phage display library approach
      thus simplifies the screening of large libraries with small numbers of (and even
      single) cells. However, the combinatorial antibodies with binding activity must
      still be tested individually by immunocytochemistry, which is further limited by
      their apparently low affinity.

PMID- 8750107
TI  - Patterns of neuropsychological impairment in mild dementia: a comparison between
      Alzheimer's disease and multi-infarct dementia.
AB  - The objective was to investigate the clinical and psychometric differences
      between patients with dementia of Alzheimer type (DAT) and patients with multi
      infarct dementia (MID), matched for age, sex, education, and severity. Sixteen
      patients with DAT, 16 patients with MID, and 30 healthy individuals, were drawn
      from a longitudinal study on aging and dementia. Subjects with medical or
      previous mental disorders were excluded. DAT and controls with focal brain
      abnormalities on magnetic resonance imaging (MRI) were excluded. Diagnosis of
      dementia was carried out according to DSM-III-R criteria. Dementia severity was
      staged using the Clinical Dementia Rating (CDR) scale, and only patients with a
      score of 0.5-1 on CDR were studied. The main outcome measures were quantitative
      clinical scales of the assessment of global mental status, depression and
      anxiety, as well as a wide battery of neuropsychological tests for the evaluation
      of executive/conceptual functions and memory, as well as attention verbal
      ability, and visuospatial skill functions. The performance of demented patients
      compared to normal controls was affected on all measurements except for
      depression and anxiety. DAT patients showed compared to MID patients a greater
      extent of impairment on tasks assessing verbal comprehension and memory while MID
      patients were more significantly impaired on measures of frontal lobe
      functioning. Clinically matched DAT and MID patients show a differential pattern
      of neuropsychological impairment when studied in an early stage of dementia and
      with a mild degree of severity. Such patterns might be of value for the
      development of clinical diagnostic criteria.

PMID- 8750108
TI  - Parkinson's disease epidemiology in the Northampton District, England, 1992.
AB  - In a population of 302,000, in a Midlands district of England, the estimated
      prevalence of idiopathic Parkinson's disease (IPD) increased from 108 to 121 per
      100,000 from 1982 to 1992. Individual general practice prevalence ranged quite
      widely. Webster ratings were significantly more often scored in 1992, but at a
      lower level of severity, suggesting earlier diagnosis. Incidence in 1992 was
      estimated as 12 per 100,000 per annum. Micrographia, when copying interlocking
      pentagons, was significantly related to Hoehn & Yahr scores. Over the 10-year
      period, there has been a considerable change in prescribing: a positive response
      to medication was confirmed as a good diagnostic indicator. Progression of
      symptoms and an increase of physical disability was noted in those of the 1982
      study alive in 1992.

PMID- 8750109
TI  - Plasma levels of the beta-carbolines harman and norharman in Parkinson's disease.
AB  - Several lines of evidence suggest that endogenous and exogenous toxins may play a
      major role in the pathogenesis of Parkinson's disease (PD). In vivo aromatic beta
      carbolines, like harman or norharman, may easily be formed by cyclization of
      indoleamines with e.g. aldehydes. Because of the structural similarity to MPTP,
      beta-carbolines have been proposed as endogenous toxins. For further elucidation
      of the role of beta-carbolines in neurodegenerative disorders, harman and
      norharman plasma levels were measured in 36 patients with PD and compared to an
      age- and sex-matched control group. Plasma levels of norharman in PD were
      significantly higher compared to the control group. Harman in the plasma of
      Parkinsonian patients was also elevated compared to controls, but this difference
      was not significant. Correlation of beta-carbolines with plasma levels of L-dopa,
      oral doses of bromocriptine and selegiline in treated Parkinsonian patients
      showed no significant results. On the one hand these results may suggest a
      possible role of beta-carbolines in the pathophysiological processes initiating
      PD, by, e.g., inducing mitochondrial respiratory inhibition like MPP+. One may
      speculate, however, that elevated levels of norharman and harman are due to an
      endogenous upregulation caused by unknown metabolic processes.

PMID- 8750110
TI  - Age at onset: the major determinant of outcome in Parkinson's disease.
AB  - Factors at presentation which influenced the course of the disease and response
      to treatment were assessed in 125 de novo patients with Parkinson's disease.
      Ninety-eight patients were available for re-assessment at 5 years. Older patients
      presented earlier after the onset of symptoms, deteriorated more rapidly, and
      were significantly more likely to develop dementia and impairment of balance.
      Increasing age and symmetrical disease predicted the new appearance of imbalance.
      Age of onset did not predict dyskinesia or end of dose failure. A low tremor
      score at baseline and female gender were predictive of the early appearance of
      dyskinesia. Patients who experienced end of dose failure were taking a
      significantly higher dose of levodopa. Once dose and duration of treatment were
      corrected for, no baseline features were predictive of end of dose failure. The
      dose of levodopa at 5 years was positively correlated to baseline disease
      severity as measured by the Columbia score. We conclude that the age of onset of
      symptoms of Parkinson's disease is a major determinant of the course of the
      disease and response to treatment.

PMID- 8750111
TI  - Frequency of CYP2D6 allelic variants in multiple sclerosis.
AB  - Recent reports have shown association between CYP2D6 polymorphism and neuronal
      degenerative diseases such as Parkinson's disease. We investigated the
      association between this polymorphism and the risk for developing multiple
      sclerosis (MS). Leucocyte DNA from 118 MS patients and a control group of 200
      unrelated healthy individuals was studied for the occurrence of 8 different
      CYP2D6 allelic variants by using allele-specific PCR amplification, XbaI and
      EcoRI RFLP analyses. The frequencies for these allelic variants in the MS and
      control groups were, respectively: CYP2D6wt 75.0% and 79.3%, CYP2D6A 0.4% and
      1.3%, CYP2D6B 11.4% and 12.0%, CYP2D6C 4.2% and 2.0%, CYP2D6D 3.0% and 2.3%,
      CYP2D6L 0.8% and 0.3%, CYP2D6L2 5.1% and 3.0%. The frequencies of subjects with
      high CYP2D6 activity (those carrying two or more functional genes) were 77.1% and
      73.5% in MS and control groups. The frequencies of subjects with absent CYP2D6
      activity (those lacking functional genes) were 3.4% and 4.5% in MS and control
      groups, respectively. These results indicate that mutations at the CYP2D6 gene do
      not seem to be a factor in determining susceptibility to MS.

PMID- 8750112
TI  - CSF oligoclonal bands, MRI, and the diagnosis of multiple sclerosis.
AB  - In this retrospective study, the results from investigations (MRI, evoked
      potentials, alkaline oligoclonal bands [OBs] in CSF) in 94 patients with clinical
      suspicion of demyelinative disease were evaluated to assess their impact on
      diagnosis. Forty-three patients were diagnosed as having definite MS, 10 probable
      MS, and 9 possible MS. MRI findings strongly suggestive of MS were evident in
      52/62 (84%) patients, while 47/62 (76%) patients demonstrated OBs in their CSF.
      In 63% of patients both abnormalities were present. Patients with no OBs in their
      CSF were on the average older, were more often male, had experienced their first
      symptoms at a later age, and suffered more often from the chronic-progressive
      form of the disease than those with a positive CSF finding.

PMID- 8750113
TI  - Can absence status epilepticus be of frontal lobe origin?
AB  - Five women with an unclassifiable nonconvulsive status epilepticus (NCSE)
      characterized by young age at onset, prolonged confusions, focal motor seizures,
      and both generalized spike-and-wave discharges and focal epileptic discharges on
      the EEG were studied with video-EEG monitoring. Electrographically, the NCSE
      originated from the left frontal lobe in 4 patients, and the left hemisphere with
      multifocal seizure discharges in 1 patient. Focal motor seizures seemed to
      originate from the left hemisphere in all 5 patients, particularly from its
      anterior part in 3 of them. Results show that the NCSE is complex partial status
      epilepticus of frontal lobe origin electroclinically mimicking absence status
      epilepticus once it reaches a full-blown phase.

PMID- 8750114
TI  - Spinocerebellar ataxia type 1: Clinical and neurophysiological characteristics in
      German kindreds.
AB  - Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative
      disorder caused by the expansion of an unstable (CAG)n repeat on chromosome 6p.
      We investigated 36 German families suffering from hereditary ataxias for the SCA1
      mutation and elaborated clinical and neurophysiological characteristics. SCA1
      accounts for 10-15% of dominant cerebellar ataxias in German kindreds. The
      clinical presentation is characterized by broad, even intrafamilial variability
      and multiple system involvement already in early stages. Slowed saccades, ptosis
      and facial weakness are more prevalent in SCA1 but were unspecific differences
      compared to non-SCA1 ataxias. Two electrophysiological parameters characterize
      SCA1: markedly prolonged central motor conduction time in motor evoked potentials
      and predominantly demyelinating polyneuropathy. Molecular genetic analyses are
      indispensable to diagnose SCA patients precisely. Extensive neurophysiological
      studies are recommendable in the clinical approach as they are suitable to
      discover subclinical damage of the nervous system. In contrast to the enormous
      variability of clinical signs in SCA1 neurophysiological findings are rather
      constant.

PMID- 8750115
TI  - Vibrameter testing facilitates the diagnosis of uremic and alcoholic
      polyneuropathy.
AB  - The diagnostic sensitivity of Vibrameter and tuning fork examination towards
      uremic and alcoholic neuropathy was tested in 75 patients. In 40 uremic and 35
      alcoholic patients, we compared the sensitivity of neurological examination,
      nerve conduction studies (NCS) and vibration thresholds assessed at the malleoli
      by means of Vibrameter and scaled tuning fork. Vibrameter results were correlated
      with NCS. Polyneuropathy was diagnosed in 52 patients, but in 16 patients
      diagnosis depended upon inclusion of Vibrameter testing in the examination
      protocol. In uremic patients, Vibrameter (47.5%) showed abnormalities as often as
      NCS (45%), and more often than clinical (32.5%) or tuning fork examination
      (2.5%). In alcoholic patients, Vibrameter revealed abnormalities more often (60%)
      than NCS (34.3%) or tuning fork (14.3%). Correlations between NCS and vibratory
      thresholds were low (-0.52 < or = Rs < or = -0.35). Vibrameter studies are far
      more sensitive than tuning fork tests. The technique complements NCS and refines
      the diagnosis of uremic and alcoholic neuropathies.

PMID- 8750116
TI  - Changes of local cerebral blood flow concomitant to lead-exposure in adult
      rabbits.
AB  - Lead is considered a pathogenic factor of atherosclerosis and arterial
      hypertension, which are main risk factors of cerebrovascular disease. The brain
      microvasculature preferentially accumulates lead and its function is sensitive to
      its toxic effect. Influence of inorganic lead-exposure (20 mg/kg-I group, 40
      mg/kg II group) for 10 days on local cerebral blood flow (lCBF) in hypothalamus
      (HYP) and cerebral cortex (CTX) of rabbits was studied by means of the hydrogen
      clearance method. Corresponding results were compared to sham operated group (III
      group). During lead-exposure lCBF was reduced in both investigated regions. The
      reduction of lCBF in HYP was reduced in both investigated regions. The reduction
      of lCBF in HYP was 12.9% (P < 0.05) in I and 19.9% (P < 0.001) in II group;
      corresponding changes in CTX were -16.9% (statistically non-significant -N) in I
      and 1.4% (NS) in II group. Present finding suggest that inorganic lead induces
      cerebral microvascular dysfunction with following changes in lCBF. These
      alteration have a biphasic character Although these disturbances reveal a
      tendency towards normalization, it is possible to presume that higher
      concentrations of ingested lead cause more severe injury to endothelium of brain
      microvasculature.

PMID- 8750117
TI  - Cerebral metabolism of oxygen and glucose in a patient with MELAS syndrome.
AB  - We studied cerebral oxygen and glucose metabolism as well as cerebral blood flow
      using positron emission tomography (PET) in a case with MELAS showing dementia,
      diabetes mellitus, ataxia and lactic acidosis without any signs of stroke. This
      case, confirmed to have a point mutation at position 3243 in the transfer RNA
      gene of mitochondrial DNA, developed a stroke-like episode 8 months after the PET
      study. Uncoupling was observed between cerebral oxygen metabolism and cerebral
      blood flow with reduced fractional oxygen extraction ratio, indicating
      "hyperemia", not ischemia. The "hyperemia" may be closely related to the
      malfunction of mitochondria in aerobic energy production. A drastic decrease in
      cerebral oxygen metabolism (CMRO2) was found globally in contrast to preserved
      cerebral glucose metabolism (CMRglu), resulting in a remarkable decrease in the
      metabolic ratio (CMRO2/CMRglu). The dissociation between cerebral glucose and
      oxygen metabolism may be characteristic of MELAS.

PMID- 8750118
TI  - Associated autoimmune diseases following complete remission of myasthenia gravis.

PMID- 8750119
TI  - Down side up--a prone and partial liquid asset.

PMID- 8750120
TI  - Hemodynamic effects of partial liquid ventilation with perfluorocarbon in acute
      lung injury.
AB  - OBJECTIVE: To assess the effect of partial liquid ventilation with
      perfluorocarbons on hemodynamics and gas exchange in large pigs with induced
      acute lung injury (ALI). DESIGN: Randomized, prospective, double-control,
      experimental study. Experimental intensive care unit of a university. MATERIALS:
      Eighteen large pigs (50 +/- 5 kg body weight) with an average anterior posterior
      thoracic diameter of 24 cm and induced acute lung injury. INTERVENTIONS: All
      animals were surfactant depleted by lung lavage to a PaO2 below 100 mmHg and
      randomized to receive either perflubron (n = 6) or saline (n = 6) in five
      intratracheal doses of 5 ml/kg at 20-min intervals, or no instillation (n = 6).
      MEASUREMENTS AND RESULTS: In all animals heart rate, arterial pressures,
      pulmonary pressures, cardiac output and blood gases were recorded at 20-min
      intervals. There was no deleterious effect on any hemodynamic parameter in the
      perflubron group, whereas systolic and mean pulmonary arterial pressure values
      showed a persistent decrease after the first 5 ml/kg of perflubron, from 48.7 +/-
      14.1 to 40.8 +/- 11.7 mmHg and from 39.7 +/- 13.2 to 35.2 +/- 12.0 mmHg,
      respectively. Perflubron resulted in a significant (ANOVA P < 0.01), dose
      dependent increase in PaO2 values from 86.3 +/- 22.4 to a maximum of 342.4 +/-
      59.4 mmHg at a dose of 25 ml/kg; the other groups showed no significant increase
      in PaO2. CONCLUSIONS: Tracheal instillation of perflubron in induced ALI results
      in a dose-dependent increase in PaO2 and has no deleterious effect on hemodynamic
      parameters.

PMID- 8750121
TI  - Contribution of bronchoalveolar lavage to the diagnosis of posttraumatic
      pulmonary fat embolism.
AB  - OBJECTIVE: To verify whether the determination of the percentage of cells
      recovered by bronchoalveolar lavage and containing fat inclusions is a useful
      diagnostic tool of posttraumatic pulmonary fat embolism. DESIGN: Prospective
      study. SETTING: Surgical Intensive Care Units in two university hospitals.
      PATIENTS: 56 successive trauma patients needing prolonged postinjury mechanical
      ventilation, including 4 with clinical definite fat embolism syndrome, 5 in whom
      the diagnosis had been clinically suspected but was impossible to confirm or
      exclude before bronchoscopy, and 47 with no clinical evidence of the syndrome.
      Control groups included 8 patients without previous trauma who developed ARDS and
      6 healthy surgical patients. METHODS: Bronchoalveolar lavage was performed within
      the first post-traumatic 3 days in trauma patients, at the beginning of the
      pulmonary disease in non trauma ARDS patients and just after anesthesic induction
      in healthy ortopedic patients. The magnitude of lipid content in alveolar cells
      was compared with the clinical pattern of the pulmonary fat embolism syndrome
      retrospectively evaluated at the seventh day postinjury in trauma patients.
      RESULTS: All the patients with definite fat embolism syndrome had more than 70%
      of lavage cells containing fat droplets. The group of patients in whom the
      diagnosis of the fat embolism syndrome was suspected had percentages of fat cells
      above 30% in 4 out of 5 patients. A percentage of fat cells above 30% was only
      observed in 7 out of the 47 patients without clinical evidence of the syndrome.
      The percentage varied between 0% to 35% in the group of non trauma ARDS patients
      and between 0 to 5% in healthy surgical patients. CONCLUSION: Lipid inclusions in
      alveolar cells are common during traumatic and non-traumatic respiratory failure.
      Determination of the percentage of cells recovered by bronchoalveolar lavage and
      containing fat droplets may contribute to the diagnosis of the fat embolism
      syndrome in mechanically-ventilated trauma patients with respiratory failure
      provided that the significant threshold would be 30%.

PMID- 8750122
TI  - Pharmacokinetics and pharmacodynamics of propofol/alfentanil infusions for
      sedation in ICU patients.
AB  - OBJECTIVE: Population pharmacokinetic analysis and pharmacodynamic profile of
      propofol/alfentanil infusions for sedation and analgesia of intensive care unit
      patients for up to 24 h. DESIGN: Institutional Review Board-approved prospective
      clinical trial. SETTING: The ten-bed intensive care unit of an university
      hospital. PATIENTS: 18 consecutive patients (ten men/eight women; age: 17-73
      years, mean 51.6 +/- 16.7 years, SD; body weight: 60-110 kg, mean 82.9 +/- 11.2
      kg, SD) requiring mechanical ventilation and prolonged sedation/analgesia after
      major surgery or trauma. INTERVENTIONS: Plasma propofol and alfentanil
      concentrations were measured at regular intervals during the long-term drug
      infusion using a high-performance liquid chromatography (propofol) and
      radioimmunoassay (alfentanil) analysis. The depth of sedation was controlled by
      monitoring a two-lead online EEG. Thus, drug application was computer controlled
      via a closed-loop EEG median-frequency feedback system. RESULTS: ICU long-term
      infusion population pharmacokinetics (open three-compartment model) revealed for
      propofol: central compartment distribution volume (V1): 31.2 +/- 5.3 l; steady
      state distribution volume (Vdss): 499 +/- 173 l; total clearance (Cltot): 1001-
      +/- 150 ml/min; redistribution half-life (t1/2 gamma): 90 +/- 23 min; elimination
      half-life (t1/2 beta): 558 +/- 218 minutes. For alfentanil: V1: 31.9 +/- 10.1 l;
      Vdss: 124 +/- 41 l; Cltot: 345 +/- 70 ml/min; t1/2 gamma: 36 +/- 15 min; t1/2
      beta: 275 +/- 94 min, respectively. CONCLUSIONS: The population pharmacokinetic
      analysis of propofol/alfentanil for ICU sedation therapy revealed increased
      volumes of drug distribution and decreased elimination characteristics as
      compared to pharmacokinetic data from short-term infusions in surgical patients.
      This can be attributed in part to altered distribution/redistribution processes
      and/or drug elimination under the condition of ICU therapy. No significant drug
      accumulation was observed. For future long-term sedation and analgesia of ICU
      patients with propofol/alfentanil, this altered pharmacokinetic behaviour should
      be taken into consideration to allow a more individualized and safer dosing of
      this drug combination.

PMID- 8750123
TI  - Cytokine and coagulation characteristics of retrieved blood after arthroplasty.
AB  - OBJECTIVES: To investigate cytokine and coagulation/fibrinolysis characteristics
      in blood retrieved from wounds using an autotransfusion system, and to compare
      the cytokine pattern in the retrieved blood with those in the systemic
      circulation and in the initial portion of drainage blood from the wound. DESIGN:
      Prospective controlled clinical study. SETTING: The postoperative ward of a
      University hospital. PATIENTS AND PARTICIPANTS: Blood retrieval was performed
      over a period of 4-6 h on patients who had just undergone arthroplasty (nine
      hips, one knee). In five other cases involving hip arthroplasties, the initial
      portion of drainage blood was studied. MEASUREMENTS AND RESULTS:
      Coagulation/fibrinolysis parameters were analyzed in blood retrieved using the
      Stryker Consta Vac system. Concentrations of tumor necrosis factor alpha (TNF),
      interleukin-1 beta (IL-1) and interleukin-6 (IL-6) were analyzed in the retrieved
      blood, in the systemic circulation of the patients at the beginning and at the
      end of blood retrieval and in the initial portion of drainage blood from the
      surgical area. In the retrieved blood, the activities of thrombin, kallikrein and
      plasmin were increased, antithrombin and free protein S were decreased, and in
      all samples IL-6 was >1000 pg/ml. Postoperative plasma concentrations of IL-6
      rose from a median value of 0 to 116 pg/ml (p <0.01). Four patients had
      circulating TNF concentrations (range: <15-50 pg/ml). Plasma IL-1 was not
      detected. TNF and IL-1 were detected in all samples of initial blood from the
      surgical area and IL-6 in one sample. CONCLUSION: Hypercoagulability and high
      concentrations of IL-6 were present in the retrieved blood. The cytokine pattern
      in the initial portion of blood from the surgical area differed from those in the
      retrieved blood and in the systemic circulation.

PMID- 8750124
TI  - Use of pulsed-field gel electrophoresis as an epidemiologic tool during an
      outbreak of Pseudomonas aeruginosa lung infections in an intensive care unit.
AB  - OBJECTIVE: A retrospective study was performed to evaluate the use of DNA
      polymorphism analysis by pulsed-field gel electrophoresis (PFGE) in assessing the
      rate of exogenous contamination during an outbreak of Pseudomonas aeruginosa lung
      infections in an intensive care unit ICU. Another goal was to determine the risk
      factors, involved in the outbreak. DESIGN: Rectal swabs and tracheal secretions
      were cultured from all patients upon admission and thereafter once a week
      throughout their stay in the ICU. Resistance patterns were determined in all P.
      aeruginosa isolates. We determined the serotypes, pyocin types, plasmid profiles
      and total DNA macrorestriction patterns for isolates. The restriction fragment
      length polymorphism (RFLP) of Dra I total DNA digest was studied by PFGE. A
      retrospective case-control study was performed to determine the risk factors for
      P. aeruginosa bronchopulmonary colonization. SETTING: The study was carried out
      in the medical ICU of Besancon University Hospital (France). RESULTS: The
      typability, stability and reproducibility of phenotypic markers were not
      completely satisfactory. Only the RFLP profile satisfied all the criteria for a
      good typing technique. In four of the 17 patients, P. aeruginosa strains with the
      same DNA pattern were found. Among the previously reported risk factors for
      hospital-acquired bronchopulmonary infections, only invasive procedures were
      determined by multivariate analysis to be significant in our study group. The
      oropharynx and the bronchial tract are the most likely endogenous sources.
      CONCLUSION: PFGE-RFLP is a valuable tool for the epidemiologic study of P.
      aeruginosa. This typing method revealed that exogenous contamination is not
      always the major source of P. aeruginosa lung infections in mechanically
      ventilated patients in ICUs.

PMID- 8750125
TI  - Tranexamic acid attenuates oleic-acid-induced pulmonary extravasation.
AB  - OBJECTIVE: Activation of fibrinolysis is implicated in the development of
      vascular injury in certain lung injuries. It has yet to be reported that
      activation of plasmin is involved in extravasation caused by oleic acid (OA). We
      examined whether or not plasmin is involved in pulmonary extravasation by OA.
      DESIGN: Prospective trial. SETTING: University laboratory. SUBJECTS: A total of
      78 guinea pigs (498.9 +/- 10.6 g). INTERVENTIONS: Evans blue (EB) was
      administered to anesthetized guinea pigs. Subsequently four protocols were
      followed: (1) After 1 min, 60 micro l/kg of OA was injected. Perfusion was
      performed 30, 60 or 90 min after OA injection to wash out intravascular EB. (2)
      After 1 min, 15, 30 or 60 micro l/kg of OA was injected. (3) Tranexamic acid (TA)
      (2 g/kg) or saline was administered 30 min before OA (15 micro l/kg) injection.
      (4) Diphenhydramine hydrochloride (2.9 mg/kg) or saline was administered 7 min
      before OA (15 micro l/kg) injection. MEASUREMENT AND RESULTS: Except in protocol
      1, the chest cavity was opened 90 min after OA injection. Perfusion was then
      performed. Airway was separated into four parts from trachea to distal bronchus.
      EB was extracted from the tissues and measured. OA caused an extravasation
      throughout airways in a time- and dose-dependent manner. Extravasation was more
      conspicuous in peripheral tissues. TA significantly attenuated extravasation,
      while diphenhydramine hydrochloride did not. CONCLUSIONS: It is suggested that
      plasmin, but not histamine, is involved in extravasation by OA. Inhibition of
      plasmin can be an effective strategy for treatment of this kind of lung injury.

PMID- 8750126
TI  - Alternating versus synchronous ventilation of left and right lungs in piglets.
AB  - OBJECTIVE: We tested whether alternating ventilation (AV) of each lung (i.e. with
      a phase difference of half a ventilatory cycle) would decrease central venous
      pressure and so increase cardiac output when compared with simultaneous
      ventilation (SV) of both lungs. THEORY: If, during AV, the inflated lung expands
      partly via compression of the opposite lung, mean lung volume will be smaller
      during AV than SV. As a consequence, mean intrathoracic pressure (as cited in the
      literature), and therefore, central venous pressure will be smaller. DESIGN: The
      experiments were performed in seven anaesthetized and paralyzed piglets using a
      double-piston ventilator. Minute ventilation was the same during AV and SV.
      Starting at SV, we alternated three times between AV and SV for periods of 10
      min. RESULTS: During AV, central venous pressure was decreased by 0.7 mmHg and
      cardiac output was increased by 10 +/- 4.4% (mean, +/-SD) compared with SV. AV
      also resulted in increased arterial pressure. During one-sided inflation with
      closed outlet of the opposite lung, a pressure rise occurred in the opposite
      lung, indicating compression. CONCLUSION: The higher cardiac output during AV
      than SV can be explained by the fact that central venous pressure is lower during
      AV. This lower central venous pressure is very probably due to the lower mean
      intrathoracic pressure caused by compression of the opposite lung during
      unilateral inflation.

PMID- 8750127
TI  - Glucose dynamics during continuous hemodiafiltration and total parenteral
      nutrition.
AB  - OBJECTIVE: To determine glucose balance during dextrose-free continuous
      hemodiafiltration with or without dextrose-containing ultrafiltrate replacement
      fluid and full nutritional support. DESIGN: Prospective, nonrandomized,
      observational study. SETTING: A 24-bed multiple trauma critical care unit in a
      level-I trauma center. PATIENTS: Seventeen multiple trauma patients with multiple
      organ dysfunction syndrome requiring hemodialysis for acute renal failure.
      INTERVENTIONS: Continuous hemodiafiltration effluent volume and glucose
      concentration were measured. Study days were classified according to whether
      dextrose was used in the ultrafiltrate replacement therapy. Use of dextrose in
      replacement therapy was determined clinically. Parenteral nutrition was not
      altered for potential glucose absorption from continuous hemodiafiltration.
      Ultrafiltrate replacement consisted of 5% dextrose in saline on 21 study days
      (D5YES) and dextrose-free solutions on 54 study days (D5NO). RESULTS: The D5YES
      group received 316 +/- 145 g glucose/day from the ultrafiltrate replacement
      fluid, in addition to glucose in total parenteral nutrition (total glucose intake
      = 942 +/- 229 g/day in D5YES, 682 +/- 154 g/day in D5NO) (p < 0.05). Glucose loss
      in continuous hemodiafiltration effluent was 82 +/- 61 g/day in D5YES and 57 +/-
      22 g/day in D5NO (P < 0.05), for a net glucose uptake of 8.1 +/- 2.1 mg/kg per
      min in D5YES and 5.4 +/- 1.5 mg/kg per min in D5NO (p < 0.05). Glucose loss was
      predictable when dialysate and ultrafiltrate replacement fluids were dextrose
      free (R2 = 0.77), but less so when dextrose was used as ultrafiltrate replacement
      (R2 = 0.47). CONCLUSION: Dextrose-free dialysate promotes glucose loss during
      continuous hemodiafiltration, but the loss is small and predictable. Use of a
      dextrose-containing ultrafiltrate replacement fluid results in a significant
      increase in glucose intake without a commensurate increase in glucose loss, and
      makes glucose loss in effluent less predictable.

PMID- 8750128
TI  - Superimposed inspiratory work of the Siemens Servo 300 ventilator during
      continuous positive airway pressure.
AB  - OBJECTIVE: To compare the superimposed inspired work of breathing (SIW) of the
      Siemens Servo 300 ventilator with the Siemens Servo 900 C ventilator. DESIGN:
      Comparisons made at continuous positive airway pressure (CPAP) levels of 0, 4,
      and 8 cmH2O, and at trigger sensitivities of -1 and -2 cmH2O, and flow
      triggering. SETTING: General intensive care unit in a University teaching
      hospital. PATIENTS: 7 patients receiving CPAP. At all levels of CPAP, the SIW was
      significantly less with the Siemens Servo 300 ventilator as compared to the
      Siemens Servo 900 C ventilator despite similar trigger sensitivities. No
      significant difference was found in the SIW of the Servo 300 ventilator when
      comparing trigger sensitivities of -1 cmH2O, -2 cmH2O, and flow triggering.
      Different levels of CPAP had no effect on SIW. CONCLUSIONS: The Siemens Servo 300
      ventilator entails less superimposed inspiratory work of breathing than the
      Siemens Servo 900 C ventilator.

PMID- 8750129
TI  - Short-term effects of methylene blue on hemodynamics and gas exchange in humans
      with septic shock.
AB  - OBJECTIVE: The aim of this study was to investigate the acute effects of
      methylene blue (MB), an inhibitor of the L-arginine nitric oxide pathway, in
      patients with septic shock. DESIGN: A prospective, open, single-dose study.
      SETTING: The medical ICU of a university hospital. PATIENTS: Six patients with
      severe septic shock. INTERVENTIONS: Complete hemodynamic values were recorded
      before and 20 min after the infusion of intravenous MB (3 mg kg(-1)). Arterial
      pressure was then monitored during the next 24 h or until death. MEASUREMENTS AND
      RESULTS: Methylene blue increased the mean arterial pressure from 69.7 +/- 4.5 to
      83.7 +/- 5.1 mmHg (p = 0.028) and the mean pulmonary artery pressure, from 34.3
      +/- 7.2 to 38.7 +/- 8.0 mmHg (p = 0.023). Systemic vascular resistance index was
      increased from 703.1 +/- 120.6 to 903.7 +/- 152.2 dyne.s.cm(-5).m(-2) (p = 0.028)
      and pulmonary vascular resistance index, from 254.6 +/- 96.9 to 342.2 +/- 118.9
      dyne.s.cm(-5) .m(-2) (p = 0.027). The PaO2/FIO2 decreased from 229.2 +/- 54.4 to
      162.2 +/- 44.1 mmHg (p = 0.028), without significant modification of
      intrapulmonary shunting. Heart rate, cardiac index, right atrial pressure, DO2,
      VO2, oxygen extraction and arterial lactate were essentially unchanged.
      Sequential measurements of arterial pressure demonstrated a return to baseline
      level in 2-3 h. All but one patients died, three in shock and two in multiple
      organ failure. CONCLUSIONS: MB induces systemic and pulmonary vasoconstriction in
      patients with septic shock, without significant decrease in cardiac index. The
      worsening of arterial oxygenation following MB injection may limit its use in
      patients with the adult respiratory distress syndrome. Larger studies are
      required to determine whether MB improves the outcome of patients with septic
      shock.

PMID- 8750130
TI  - Secondary exposure of medical staff to sarin vapor in the emergency room.
AB  - OBJECTIVE: To clarify the risk of secondary exposure of medical staff to sarin
      vapor in the emergency room, and to warn emergency room staffs of the hazard.
      DESIGN: Retrospective observational survey. SETTING: Emergency department of a
      university hospital in a metropolitan area of Japan. PARTICIPANTS: Fifteen
      doctors treating victims of a terrorist attack with sarin in the Tokyo subways on
      the day of the attack. MEASUREMENTS AND RESULTS: Of the 15 doctors who worked in
      the emergency room treating the victims, 13 became simultaneously aware of
      symptoms during the resuscitation of two victims who were exposed to sarin. Among
      11 doctors (73%) who complained of dim vision, the pupils were severely miotic
      (<2 mm) in 8 (73%). Other symptoms included rhinorrhea in eight (53%), dyspnea or
      tightness of the chest in four (27%), and cough in two (13%). Atropine sulfate
      was given to six, and pralidoxime was given to one of these six doctors. To
      decontaminate the emergency room of sarin vapor, ventilation was facilitated and
      all belongings of the patients were sealed up. None of the doctors noticed
      worsening of their symptoms thereafter. CONCLUSIONS: Careful attention to the
      risks of secondary exposure to toxic gas in the emergency room and prompt
      decontamination if such exposure should occur are necessary in the case of large
      scale disasters caused by sarin.

PMID- 8750131
TI  - Testicular choriocarcinoma revealed by a localized pulmonary edema: a case
      report.
AB  - We report the case of a young man hospitalized because of an acute pulmonary
      embolism presenting as a focal pulmonary edema, without evidence of left
      ventricular failure. This pulmonary embolism was caused by a testicular
      choriocarcinoma that entailed both a neoplastic venous involvement with pulmonary
      neoplastic embolism, and a compression of inferior vena cava with thrombosis and
      subsequent pulmonary thromboembolism. This case combines two unusual
      associations: (i) Pulmonary embolism causing a localized pulmonary edema, (ii)
      Neoplastic pulmonary embolism of a testicular choriocarcinoma.

PMID- 8750132
TI  - A case of life-threatening lactic acidosis after smoke inhalation - interference
      between beta-adrenergic agents and ethanol?
AB  - A 49-year-old male developed bronchospasm and severe lactic acidosis after
      exposition to fire smoke. The correction of lactic acidosis following beta
      adrenergic agents withdrawal, and the transitory increase in lactate after
      salbutamol reintroduction are consistent with hypersensitivity to salbutamol.
      However, the plasma lactate concentration (32.6 mmol/l) that we observed 9.5 h
      after admission is far above those currently seen after administration of beta
      adrenergic agents. We searched for causes able to potentiate the adverse effects
      of these drugs and we noticed that our patient had a high plasma ethanol level
      (2.4 g/l). Alcohol metabolism in the liver results in generation of high
      NADH/NAD+ ratios, thus reducing lactate liver clearance. This observation
      suggests that plasma lactate levels should be monitored closely in alcoholic
      patients treated with beta-mimetic agents.

PMID- 8750133
TI  - Arteriovenous fistulae complicating central venous catheterization: value of
      endovascular treatment based on a series of seven cases.
AB  - OBJECTIVES: To point out the usefulness and effication of endovascular treatment
      of arteriovenous fistulae complicating the insertion of central venous catheter.
      MATERIAL AND METHOD: Retrospective study of 7 cases treated between 1983 and
      1993. The central venous catheterization had involved the right internal jugular
      vein in 5 cases and the right subclavian vein in 2 cases. RESULTS: Isolated
      endovascular therapy was performed in 5 cases. Surgery was necessary in 1 case to
      remove an hematoma. In another case, occlusion of a large AVF was performed
      during intraoperative endovascular temporary occlusion of the AVF. The choice of
      the occluding agent was primarily dictated by the hemodynamic and anatomical
      conditions (releasable balloons, coils). Vertebro-vertebral fistulae (3 cases)
      could be treated with patency of this vessel. No complications were encountered.
      CONCLUSION: Endovascular approach is a reliable and safe method to perform
      occlusion of post catheter AVF.

PMID- 8750134
TI  - Postobstructive pulmonary edema induced by endotracheal tube occlusion.
AB  - Pulmonary edema is a well-described complication of upper airway obstruction,
      most commonly caused in adults by postanesthetic laryngospasm. The mechanism
      initiating the formation of postobstructive pulmonary edema is believed to be the
      markedly negative intrapleural pressure generated by a forceful inspiratory
      effort against an obstructed extrathoracic airway. We herein describe a young,
      male patient who developed pulmonary edema postoperatively, upon emergence from
      anesthesia, after performing repeated, forceful inspiratory maneuvers directed
      against an endotracheal tube on which he had bitten down, thereby occluding it.
      To our knowledge, such an etiology of postobstructive pulmonary edema has not
      previously been described.

PMID- 8750135
TI  - Mercury oxycyanide and mercuric cyanide poisoning: two cases.
AB  - BACKGROUND: Although cyanide poisoning can be serious or fatal, it is typically
      described as mild when the cyanide is ingested in the form of either mercuric
      cyanide or mercury oxycyanide. METHODS: We studied two patients with acute
      cyanide poisoning following ingestion of one of these two agents in each case.
      RESULTS: Both patients demonstrated features of life-threatening cyanide
      poisoning, including hemodynamic instability, severe lactic acidosis, and high
      blood cyanide concentration. One of the patients died, while the second
      demonstrated signs of mercury intoxication (acute renal failure and severe
      gastrointestinal symptoms), in addition to cyanide intoxication. CONCLUSION:
      Ingestion of either mercuric cyanide or mercury oxycyanide can result in life
      threatening cyanide intoxication.

PMID- 8750136
TI  - Pressure control ventilation and minitracheotomy in treating severe flail chest
      trauma.
AB  - OBJECTIVE: To evaluate pressure control ventilation (PCV) delivered through a
      minitracheotomy in treating severe flail chest trauma. DESIGN: Case report.
      SETTING: Intensive care unit of a trauma center. PATIENT: A 34-year-old woman
      affected by flail chest trauma and acute respiratory failure, who was initially
      treated with tracheal intubation to obtain internal pneumatic stabilization. The
      patient failed extubation and noninvasive mask treatment (pressure support
      ventilation plus PEEP) due to poor chestwall mechanics. INTERVENTIONS:
      Minitracheotomy was performed and ventilation was achieved with high levels of
      inspiratory pressure (PCV or assisted PCV) to overcome the resistance of the
      cannula (Mini-Trach II, Portex, ID 4 mm). Esophageal and carinal pressures were
      monitored. Ventilatory treatment was always performed with the full cooperation
      of the patient; the patient's glottic function was always intact. The patient was
      successfully treated with pressure control ventilation delivered through the Mini
      Trach. After 7 days of PCV, the patient was switched to assisted PCV. On the 20th
      day after admission, she was weaned from mechanical ventilation. CONCLUSIONS: We
      conclude that a suitable gas exchange and pneumatic stabilization in a flail
      chest condition can be achieved using minitracheostomic ventilation. At the same
      time, this treatment could reduce some side effects of traditional tracheal
      intubation.

PMID- 8750137
TI  - Haematological support of high-dose sequential chemotherapy: clinical evidence
      for reduction of toxicity and high response rates in poor risk lymphomas.
AB  - The toxicity and feasibility of a high-dose sequential (HDS) chemotherapy
      programme delivered with growth factor support were evaluated in patients with
      intermediate and high-grade non-Hodgkin's lymphoma (NHL) or with progressive
      Hodgkin's disease. The scheme includes the sequential administration of single
      cytotoxic drugs at very high doses followed by intensified treatment with
      circulating progenitor autograft. In some instances, the original HDS scheme,
      initially designed at the Milan Cancer Center, was partially modified and
      intensified with a preliminary debulking phase. The use of G-CSF (filgrastim)
      made toxicity in the high-dose phase acceptable and allowed good harvests of
      peripheral blood progenitor cells (PBPC); the use of PBPC in the final
      autografting phase resulted in low haematological toxicity. Of 71 patients with
      NHL treated at our institution with either the original or the intensified HDS
      version, the overall toxicity-related mortality was 5.6%, thus comparable to
      lethal toxicity commonly associated with conventional chemotherapy. Adequate PBPC
      harvests are crucial for good tolerability of the programme. Optimal harvests are
      generally obtained in patients without neoplastic marrow infiltration while
      patients with marrow disease often have a poorer mobilisation. However, an
      optimally time-spaced chemotherapy debulking might also restore sufficient
      mobilisation in these latter patients. In terms of therapeutic efficacy, HDS had
      produced promising results since the initial experience in relapsed patients.
      More recently, HDS was evaluated as first-line treatment in a series of 22
      consecutive patients, presenting with advanced-stage, intermediate-grade NHL
      other than diffuse large cell subtype. A CR rate of 82% was obtained following
      HDS, with a projected survival of 86% at five years. Thus, delivery of an
      intensive high-dose chemotherapy programme with haematopoietic growth factor
      support was found to be feasible and reasonably safe. The high anti-tumour
      efficacy of such a scheme makes it suitable for wider applicability in all those
      chemosensitive tumours where a dose increase might enhance the chance of cure.

PMID- 8750138
TI  - Practical applications for peripheral blood progenitor cells in the treatment of
      lymphomas and solid tumours.
AB  - Autologous blood progenitor cell (BPC) support is used in conjunction with high
      dose chemotherapy regimens and also permits the use of increasing dose-intensity
      schedules of conventional cytotoxic chemotherapy. However, our understanding of
      the optimal BPC support to be used in these different conditions is incomplete.
      These difficulties result from the use of different BPC collection procedures in
      different centres, to different patient populations and considerable variability
      between patients. For such treatment to be cost effective, greater knowledge is
      required about the best way of achieving mobilisation, collection, storage and
      engraftment of BPC. The use of G-CSF in combination with chemotherapy can yield
      sufficient BPC at a single apheresis to achieve haematopoietic reconstitution
      after high-dose therapy. This was partly achieved by accurate prediction of the
      optimum timing of cell collection, which coincided with the early exponential
      increase in white blood cells (WBC) after the chemotherapy induced nadir. BPC in
      apheresis product or whole blood from patients primed with chemotherapy and
      filgrastim (G-CSF) were found to be viable for 48 hours when stored at 4 degrees
      C. Patients receiving multicyclic ifosfamide, carboplatin and etoposide (ICE)
      chemotherapy received BPC in apheresis product or whole blood, which had been
      stored at 4 degrees C, on day 3 of each treatment cycle. Such an approach allowed
      a 200% increase in dose intensity without any increase in toxicity or the need
      for supportive care. Optimal use of BPC support may increase the effectiveness of
      chemotherapy for the common solid tumours.

PMID- 8750139
TI  - New strategies for the application of high-dose chemotherapy with haematopoietic
      support in paediatric solid tumours.
AB  - Because paediatric solid tumours are usually highly chemosensitive, conventional
      dose adjuvant chemotherapy has improved survival rates for the majority of
      paediatric patients. However, high-dose regimens are being explored for the
      treatment of tumours not curable by, or resistant to, conventional treatment. The
      use of high-dose melphalan and the BACT regime have produced encouraging results
      in neuroblastoma and Ewing's sarcoma, and non-Hodgkin's lymphoma respectively.
      Haematopoietic growth factors have also emerged as useful adjuncts both to
      conventional therapy and in megatherapy with bone marrow transplantation (BMT).
      Thus, granulocyte colony-stimulating factor (G-CSF) (filgrastim) given to
      children with disseminated neuroblastoma receiving intensive chemotherapy
      significantly reduced the duration of febrile neutropenia and led to
      significantly fewer cycles of chemotherapy requiring antibiotic support. Studies
      are currently underway to compare the use of autologous BMT with that of
      peripheral blood progenitor cell (PBPC) rescue in children with solid tumours
      receiving high-dose chemotherapy. The studies will explore the reduction in
      thrombocytopenia achievable with PBPC and also the effect of filgrastim on the
      duration of neutropenia and fever. It seems that haematopoietic growth factors
      have an important supportive role to play in the treatment of paediatric solid
      tumours.

PMID- 8750140
TI  - Overview of peripheral blood progenitor cell usage in France.
AB  - Peripheral blood progenitor cell (PBPC) transplantation offers a number of
      advantages over the use of bone marrow (BM) cells. Both the number and percentage
      of transplants performed with blood cells in France increased dramatically from
      1990 to 1992. This report presents an analysis of 573 patients who underwent
      autologous transplantation of PBPC without BM. Approximately 50% received total
      body irradiation (TBI) and 12% received busulphan (Bu). The 200 patients
      receiving haematopoietic growth factors (HGF) for mobilisation showed an increase
      in the number of CFU-GM and CD34+ cells collected. Multivariate analysis showed
      that granulocyte recovery was significantly influenced, positively, by the number
      of CFU-GM cells infused, and by the use of HGF both for PBPC mobilisation and
      after transplantation; and negatively by the use of Bu. Further studies are still
      required to establish whether PBPC, in addition to reducing the duration of
      marrow aplasia, will also lead to decrease in transplant-related mortality or
      morbidity.

PMID- 8750141
TI  - Potential strategies for improving the results of high-dose chemotherapy in
      patients with metastatic breast cancer.
AB  - High-dose chemotherapy (HDC) is the most effective approach for inducing complete
      remissions in patients with metastatic breast cancer, and although most patients
      will relapse, a small percentage (10%-15%) achieve durable remissions beyond five
      years. Additionally, HDC has produced five-year relapse-free survival rates in
      excess of 70% in patients with stage II breast cancer with > 10 nodes. The use of
      HDC in breast cancer remains controversial and randomised trials are required to
      assess the survival impact of this approach. The introduction of haematopoietic
      growth factors (HGF) and peripheral blood progenitor cells (PBPC) has advanced
      the use of HDC by reducing treatment-related mortality (from 20% to 5%) and by
      allowing the development of multiple cycles of intensive therapy. Based on tumour
      kinetic models we have hypothesised that multiple, rapidly cycled courses of high
      dose therapy may improve the rate of durable remission in metastatic breast
      cancer. The feasibility of this approach has been shown in a series of pilot
      studies in which one or more courses of high-dose cyclophosphamide and
      recombinant granulocyte colony-stimulating factor (G-CSF) (filgrastim) were given
      to obtain PBPC which were then used to support one or more courses of HDC. In
      successive studies the HDC component consisted of: a single course of
      carboplatin, etoposide and cyclophosphamide; four courses of carboplatin; tandem
      courses of thiotepa; or a sequence of melphalan and thiotepa. Promising response
      rates have been produced in advanced breast and ovarian cancer with the later
      generation of regiments. These results justify the conduct of prospective
      randomised trials.

PMID- 8750142
TI  - Rationale for high-dose chemotherapy and application of haematopoietic growth
      factors in acute myeloid leukaemia.
AB  - High-dose chemotherapy in acute myeloid leukaemia (AML) is more effective and not
      associated with a higher risk of lethal complications during the induction phase
      as compared with less intensive regimens. This seemingly paradoxical finding is
      explained by the more rapid reduction of the leukaemic cell mass and the faster
      restoration of normal haematopoesis. In the most recent study on double induction
      therapy by the German AML Cooperative Group involving 665 adult patients with AML
      the rate of complete remission was 66%-73%. Haematopoietic growth factors used as
      part of the anti-tumour regimen offer a number of advantages. These include
      acceleration of haematopoietic recovery and the potential to enhance the
      sensitivity of leukaemic blasts when given prior to and during cytostatic
      therapy. New perspectives to further enhance the intensity of antileukaemic
      therapy may emerge from the introduction of peripheral stem cell transplantation
      into the treatment strategy.

PMID- 8750143
TI  - High-dose chemotherapy for breast cancer: clinical advantages of autologous
      peripheral blood progenitor cells (PBPC) compared with autologous bone marrow
      transplantation (ABMT).
AB  - Peripheral blood progenitor cell (PBPC) autografts have a number of advantages
      over autologous bone marrow transplantation (ABMT) as haematopoietic support
      after high-dose chemotherapy in patients with breast cancer. These may include
      less contamination by tumour cells, reduced morbidity and mortality and
      additional dose escalation of chemotherapy. A dose-escalation study is described
      using recombinant granulocyte colony-stimulating factor (G-CSF; filgrastim)
      primed PBPC support and post-infusion filgrastim for patients with high-risk or
      metastatic breast cancer. The regimen involved the use of cyclophosphamide,
      thiotepa and carboplatin at five dose levels. The main problem to emerge was
      organ toxicity induced by chemotherapy or sepsis. Patients receiving higher
      levels of chemotherapy were therefore allocated or not to an additional regimen
      involving pentoxifylline, ciprofloxacin and dexamethasone in an attempt to
      inhibit tumour necrosis factor alpha (TNF-alpha) which is believed to be one of
      the principal mediators of chemotherapy-related organ toxicity. The incidence of
      bilirubin elevations, weight gain > 5% and veno-occlusive disease (VOD) was lower
      in patients receiving the 'anti-TNF' therapy. The simultaneous use of PBPC
      support and 'anti-TNF' therapy therefore allows a substantial increase in
      chemotherapy dosage. Further studies with larger patient numbers are required to
      show whether this decreased toxicity also produces increased patient survival.

PMID- 8750144
TI  - p53, myc, APC, hMSH2, ras, etc. in colorectal cancer - a never ending story!

PMID- 8750145
TI  - The Djerba statement: just another declaration, or a new beginning?

PMID- 8750146
TI  - Matrix metalloproteinase inhibition: a review of anti-tumour activity.
AB  - BACKGROUND: Matrix metalloproteinases are a homologous family of proteolytic
      enzymes. Collectively, these proteinases are capable of degrading all components
      of the extracellular matrix, including proteolytically resistant fibrillar
      collagens. Extracellular matrices constitute the principal barrier to tumour
      growth and spread, and there is now experimental evidence that malignant tumours
      utilise matrix metalloproteinases to overcome this barrier. Inhibitors of matrix
      metalloproteinases may therefore be of therapeutic value in the treatment of
      metastatic disease. DESIGN: This review describes the activity of matrix
      metalloproteinases inhibitors (MMPIs), in experimental tumour models and in phase
      I/II clinical studies. RESULTS: Studies with MMPIs in vitro have shown that these
      agents are not cytotoxic but can inhibit the degradation of extracellular matrix
      by tumour cells. In experimental tumour models in vivo, MMPI treatment caused
      inhibition of tumour growth and metastatic spread in both rodent syngeneic and
      human xenograft models. MMPIs have also been shown to inhibit angiogenesis, a
      process essential for the rapid growth of most malignancies. CONCLUSIONS: MMPI
      therapy has the potential to arrest tumour growth and spread. As a non-cytotoxic
      'tumourostatic' approach it may offer an ideal complement to surgery,
      radiotherapy and chemotherapy in the successful long-term treatment of metastatic
      disease.

PMID- 8750147
TI  - Cell cycle regulation and the function of cancer genes.

PMID- 8750148
TI  - Commitment demanded for lung cancer research.

PMID- 8750149
TI  - Evidence for a mutual regulation of p53 and c-myc expression in human colorectal
      cancer metastases.
AB  - BACKGROUND: Alterations of the c-myc and the p53 genes occur in a majority of
      human colorectal cancers, and functional interaction between these two genes has
      recently been suggested. PATIENTS AND METHODS: We analyzed p53 sequence and c-myc
      and p53 mRNA expression in 26 metastases and 4 advanced primaries of human
      colorectal cancer. RESULTS: Twenty-one of 30 tumors (=70%) carried mutations of
      the p53 gene. In these samples, c-myc and p53 were overexpressed in 70% (15/21)
      and 71% (14/20) of evaluable cases, respectively, while in tumors carrying only
      wild-type p53, overexpression of c-myc and p53 was observed in only 33% (3/9; p <
      0.05) and 22% (2/9; p < 0.01), respectively. Expression of p53 and c-myc were
      positively correlated (p = 0.014; r = 0.563) in tumors carrying a p53 mutation,
      but not in those with only wild-type p53. CONCLUSION: We conclude that c-myc
      might induce p53 expression in human colorectal cancer and that wild-type but not
      mutant p53 might be involved in a negative feedback regulation of c-myc
      expression. The abrogation of this normal control mechanism seems to be an
      essential step during colorectal tumorigenesis and metastatic progression.

PMID- 8750150
TI  - Treatment of recurrent and/or metastatic squamous cell head and neck carcinoma
      with a combination of vinorelbine, cisplatin, and 5-fluorouracil: a multicenter
      phase II trial.
AB  - PURPOSE: Vinorelbine has been demonstrated to be active against squamous cell
      carcinomas of the head/neck (SCHNC) and lung. This multicenter phase II trial was
      carried out to evaluate the activity and tolerability of the combination of
      vinorelbine, cisplatin, and 5-fluorouracil given on an outpatient schedule in a
      series of 80 patients with recurrent SCHNC. PATIENTS AND METHODS: Eighty patients
      with recurrent and/or metastatic SCHNC were treated with a combination of CDDP 80
      mg/m2on day 1, 5-FU 600 mg/m2 as a 4-hour infusion on days 2-5, and vinorelbine
      25 mg/m2 on days 2 + 8. This cycle was repeated every 28 days. Most patients had
      oral cavity, larynx, or oropharynx carcinoma (88%). Forty-seven had previously
      received surgery alone, two radiotherapy alone, and 31 surgery plus radiotherapy.
      Seventy-two patients had locoregional recurrency, and eight had distant
      metastases. RESULTS: According to an intent-to-treat analysis, complete response
      (CR) of a mean duration of 12.7+ months was achieved in 13% of cases (95% CI 5%
      21%), and partial response of 8.3+ months in 45% of patients (95% CI 33%-56%),
      for an overall response rate of 55% (95% CI 43%-65%). Nine patients (11%) showed
      no change, and 22 (28%) progressed. Five patients were not evaluable for response
      and toxicity. CR were seen more frequently in patients pretreated with only
      surgery than in those who had also received radiotherapy (15% vs. 9%; p = 0.7).
      No statistically significant differences in response rate according to site of
      primary tumor were found (p = 0.8, NS). The received dose intensities of 5-FU,
      CDDP, and VNR were 90%, 92%, and 82%, respectively. The overall survival of the
      series as a whole was 9.7+ months (range 4-27). Toxicity was generally
      acceptable. Grades 3 and 4 leukopenia were recorded in 11% and 5% of patients,
      respectively. Noteworthy was the occurrence of pain at the tumor site after
      vinorelbine administration in 5 patients. CONCLUSION: The combination regimen of
      CDDP, 5-FU and vinorelbine is quite active in the treatment of metastatic and/or
      recurrent SCHNC. This regimen should be tested as initial treatment in previously
      untreated patients and compared to a standard regimen in recurrent SCHNC.

PMID- 8750151
TI  - Evaluation of the optimal duration of chemotherapy in phase II trials for
      inoperable non-small-cell lung cancer (NSCLC).
AB  - PURPOSE: To determine the optimal duration of chemotherapy in phase II trials for
      patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: The time
      from start of treatment until achievement of response according to WHO criteria
      was determined retrospectively in 8 phase II trials. RESULTS: Response to
      chemotherapy consisting of 4 complete and 39 partial remissions was registered in
      43 of 333 patients. The median time from treatment start to response was 54 days.
      On day 84 on-study, 35 of the responding patients (81%) had achieved the
      response. Forty-three responses (98%) had occurred by day 168 and only one
      patient (2%) accomplished a response after 168 days of treatment. The responses
      had a median duration of 151 days (range 28-1559 days). CONCLUSIONS: The data
      indicate that patients with NSCLC included in phase II trials who have not yet
      achieved a response to chemotherapy after 168 days on study have a low likelihood
      (2%) of a subsequent response. Hence, treatment cessation at this point should be
      considered for non-responding patients. Continuation of treatment from day 84 to
      day 168 resulted in response in only 7 patients out of the total of 43 responses
      noted (16%). Thus, the toxic effects of the chemotherapy in addition to the
      inconvenience of hospital visits renders it questionable whether it is worthwhile
      to continue treatment in patients with inoperable non-small-cell lung cancer
      beyond day 84 in the absence of response.

PMID- 8750152
TI  - Randomised study using IFN-alpha versus IFN-alpha plus coumarin and cimetidine
      for treatment of advanced renal cell cancer.
AB  - BACKGROUND: Treatment results in patients with metastatic renal cell cancer (RCC)
      are still extremely unsatisfactory. Rates of response to IFN-alpha monotherapy
      and/or IL-2 mono/combination therapy vary between 10% and 20%. Coumarin (Cum)
      together with cimetidine (Cim) has yielded objective responses in 20%-33% of
      patients with RCC, according to two recent phase II studies. PATIENTS AND
      METHODS: In the present study 148 patients with metastatic RCC were randomised to
      receive either IFN-alpha (5 MU 5 x weekly s.c.) + coumarin (100 mg/d p.o.) +
      cimetidine (3 x 400 mg/d p.o.), or IFN-alpha-monotherapy (5 MU 5 x weekly s.c.).
      RESULTS: Of the 148 patients in the study 137 were evaluable for response. No
      differences in remission rates (RR IFN-alpha + Cum + Cim 17.1% and IFN-alpha
      20.8%) or survival times (median survival 9 months and 8 months, respectively)
      were found between these two treatment arms. CONCLUSIONS: This study confirms
      that INFN-alpha has antitumoral activity in RCC. Adding coumarin + cimetidine to
      IFN-alpha in the dose and regimen prescribed in this study did not increase
      response rates or survival.

PMID- 8750153
TI  - Bcl-2 protein expression in breast cancer in relation to established prognostic
      factors and other clinicopathological variables.
AB  - BACKGROUND: Bel-2 inhibits most kinds of programmed cell death and provides a
      selective survival advantage to various cell types. Bcl-2 is physiologically
      expressed in ductal epithelia of the normal breast. The biological significance
      of Bcl-2 (over)expression for the development and progression of breast cancer
      has still to be evaluated. PATIENTS AND METHODS: A series of 133 primary breast
      cancers was investigated for expression of the Bcl-2 protein by
      immunohistochemistry of paraffin-embedded tissue sections. Results were
      correlated with other variables of established or presumed predictive value.
      RESULTS: A significant positive correlation was observed between Bcl-2 expression
      and positivity for estrogen and progesterone receptors (p < 0.001). High
      proliferative activity as assessed by Ki-67 staining correlated inversely with
      Bcl-2 expression (p < 0.001). Bcl-2 immunostaining was not related to positivity
      for c-erbB-1. It was negatively associated with overexpression of c-erbB-2 (p =
      0.04), whereas a strong positive correlation was found with expression of c-erbB
      3 (p = 0.01). There was a significant inverse correlation between histological
      grading and immunoreactivity for Bcl-2 (p < 0.001). N0 tumors tended to be Bcl-2
      positive, but differences were not statistically significant. CONCLUSION: Bcl-2
      was detected predominantly in differentiated tumors. Expression was associated
      with other favorable histopathological features and predictors of positive
      clinical outcome. Loss of Bcl-2 expression seems to be linked to loss of hormonal
      regulatability, increased dedifferentiation and deregulated proliferation.

PMID- 8750154
TI  - Sequential biochemotherapy for metastatic colorectal cancer using fluorouracil,
      folinic acid, thymopentin and interleukin-2: clinical and immunological effects.
AB  - BACKGROUND: A phase II study was performed to evaluate the clinical and
      immunological effects of a regimen of fluorouracil (5-FU) and folinic acid (FA)
      combined with thymopentin (TP-5) and interleukin-2 (IL-2) in the treatment of
      patients with metastatic colorectal cancer. PATIENTS AND METHODS: Forty-five
      evaluable patients with measurable colorectal cancer and no prior therapy for
      metastatic disease were treated with 5-FU 400 mg/m2/d and FA 200 mg/m2/d i.v. on
      days 1-5, TP-5 50 mg s.c. on days 8-11, and IL-2 9 MU/m2 s.c. twice daily on days
      12-16. Cycles were repeated at 4-week intervals if toxicity had resolved.
      Immunological changes were evaluated in 13 patients and compared with a well
      matched series of 13 patients treated with the same regimen without TP-5.
      RESULTS: Two complete responses and 17 partial responses were seen (42%; 95%
      confidence interval, 28% to 56%). Fifteen patients (33%) had stable disease. The
      median time to progression was 8.5 months and the median survival 13 months.
      Treatment was reasonably well tolerated, and there was no overlapping toxicity or
      interference between chemotherapy and biotherapy. Hematological and immunological
      changes during treatment were qualitatively similar to those expected with IL-2
      +/- chemotherapy. Quantitatively, significant changes (higher levels of IL-2,
      CD25 and IFN-gamma, and lower levels of sIL-2R) were observed in patients given
      TP-5. CONCLUSION: The combination of 5-FU + FA and TP-5 + IL-2 is effective in
      advanced colorectal cancer with acceptable toxicity. Immunological data suggest
      that TP-5 may modulate the action of IL-2 in the clinical setting. However,
      improved treatment approaches are needed, and the interactions between thymic
      hormones and cytokines should be further explored.

PMID- 8750155
TI  - Vincristine, doxorubicin, cyclophosphamide, prednisone and etoposide (VACPE) in
      high-grade non-Hodgkin's lymphoma--a multicenter phase II study.
AB  - BACKGROUND: Patients with high-grade non-Hodgkin's lymphoma (NHL) can potentially
      be cured by intensive chemotherapy. However, many patients still die of their
      disease, which underscores the need to define patient groups with different long
      term prognoses and for more effective and possibly risk-adapted treatment
      approaches. PATIENTS AND METHODS: In this phase II study we investigated the
      feasibility and efficacy of a polychemotherapy consisting of 2 mg vincristine (V)
      on day 1, 25 mg/m2 doxorubicin (A) days 1-3, 800 mg cyclophosphamide (C) day 1,
      60 mg/m2 prednisone (P) days 1-7 and 120 mg/m2 etoposide (E) days 1-3. This cycle
      (VACPE) was repeated on day 22 for up to 5 cycles in stages I-III and 6 cycles in
      stage IV, respectively, followed by consolidating radiotherapy in 38/73 patients.
      A total of 75 patients with high-grade NHLs according to the Kiel classification
      were eligible, and 73 patients are evaluable for response. The predominant
      histological subtypes were centroblastic, pleomorphic T-cell and large-cell
      anaplastic lymphomas, 60% of the patients presented with stage III/IV, 55% with a
      poor performance status (ECOG > or = 2), 53% with B symptoms and 60% with a LDH
      level >200 U/l. RESULTS: 57/73 patients achieved CR (78%), and the overall
      response rate (CR-PR) was 95%. The median observation time is 40 months (10+
      74+). The 1-, 3- and 5-year overall survivals for the entire VACPE group were
      79%, 64% and 61%, respectively. Forty-one patients are in ongoing CR with a
      continuous complete remission rate (CCR) of 67%. Fourteen of the 16 patients who
      relapsed (88%) did so within the first 24 months. The predicted 1-, 3- and 5-year
      DFS for those patients who achieved CR is 83%, 67% and 67%, respectively. The
      early mortality was 3/73 (4.1%). In patients with reduced performance status the
      overall survival (OS) (ECOG > or = 2) was significantly reduced, with a predicted
      1-, 3- and 5-year survival of 62%, 49% and 49% versus 100%, 84% and 77% in
      patients with favorable performance status, respectively (p = 0.001). The
      predicted overall survival in stages III/IV is worse than in early stages with a
      1-, 3- and 5-year probability of 73%, 52% and 52% versus 90%, 86% and 78%,
      respectively (p = 0.02). Comparison of patient groups with cumulative risk
      factors shows a significant decrease in overall survival. Especially in patients
      with 0-2 risk factors versus those presenting with >2 risk factors, there is a
      significantly better 3- and 5-year survival (p = 0.002). In contrast to overall
      survival, there were no differences between the listed risk groups concerning the
      disease-free survival of complete responders. CONCLUSION: In conclusion, the
      VACPE regime is feasible and effective in high-grade NHLs and may also be
      administered on an outpatient basis. Despite encouraging data, however, a
      prospective randomized trial is warranted to define a possible superiority to
      standard CHOP. However, this regimen may be the basis for further randomized and
      risk adapted innovative approaches for high-grade NHLs.

PMID- 8750156
TI  - Chemotherapy combined with zidovudine and GM-CSF in human immunodeficiency virus
      related non-Hodgkin's lymphoma.
AB  - OBJECTIVE: The treatment of patients with non-Hodgkin's lymphoma related to the
      human immunodeficiency virus (HIV-NHL) is complicated by the underlying acquired
      immunodeficiency syndrome (AIDS). Patients without adverse prognostic factors (no
      AIDS prior to lymphoma, CD4+ lymphocyte counts greater than 100 x 10(6)/l and
      good performance status) can be cured of lymphoma and experience long-term
      survival. Our previous study with the intensive chemotherapy LNH84 regimen
      yielded a 63% complete response (CR) rate but median survival was only nine
      months, half of the patients died of AIDS and the other half of their lymphoma.
      We report here the results of a phase II study combining the same chemotherapy
      with zidovudine and GM-CSF. Our goal was to improve the treatment outcome over
      that of our previous study; GM-CSF was expected to decrease the hematological
      toxicity of chemotherapy and thus permit a dose intensity increase, while
      zidovudine was supposed to slow down the evolution of AIDS. DESIGN AND SETTING: A
      phase II non-randomized prospective clinical trial in 7 centres. PATIENTS AND
      METHODS: Thirty-two consecutive adult patients presenting HIV-NHL and performance
      status of less than three without active opportunistic infection underwent three
      cycles of doxorubicin 75 mg/m2, cyclophosphamide 1,200 mg/m2, vindesine 2 mg/m2
      for two days, bleomycin 10 mg for two days and prednisolone 60 mg/m2 for five
      days (ACVB). Chemotherapy was associated with zidovudine (5 mg/kg/d) and GM-CSF
      (5 mu g/kg/d). The induction phase was followed by a four-month consolidation
      phase. RESULTS: CR and PR > 75% were observed in 56% of patients; 25% of the
      patients died during the induction phase. These results were analogous to those
      of the previous study (63% and 14%, respectively). Neither hematological
      tolerance nor dose intensity were improved. With a mean follow-up of 23.5 months,
      median survival was 6.7 months. The rate of non-NHL AIDS-related death during CR
      was not reduced (22% in our study vs. 16% in our previous one). CONCLUSIONS: GM
      CSF failed to reduce significantly the cumulative hematological toxicity of
      chemotherapy and zidovudine. New antiviral agents without hematological toxicity
      would perhaps be useful in this setting.

PMID- 8750157
TI  - First-line systemic therapy for metastatic breast cancer and management of
      pleural effusion.

PMID- 8750158
TI  - Epirubicin + G-CSF as peripheral blood progenitor cells (PBPC) mobilising agents
      in breast cancer patients.
AB  - BACKGROUND: In an attempt to mobilise peripheral blood progenitor cells (PBPC)
      from patients with breast cancer, Epirubicin supported with G-CSF was tested.
      Another aim of the study was also to optimize the procedure so that the number of
      leukapheresis procedures could be reduced. These cells were subsequently
      reinfused as hematologic rescue after high-dose chemotherapy programs. PATIENTS
      AND METHODS: Twenty-nine patients received Epirubicin 150 mg/sqm + G-CSF at the
      dose of 5 micro/kg/bw s.c. daily, starting 24 hours after chemotherapy. Twelve
      had metastatic, eight inflammatory or locally advanced disease, and nine were
      treated in an adjuvant setting. RESULTS: The median numbers of CD34+ cells and
      CFU-GM collected were 12.9 x 106/kg/bw and 111.7 x 10(4)/kg/bw, respectively. The
      mean number of leukapheresis procedures per patient was 1.8 +/- 0.3 (range 1-3),
      and the mean day of the first procedure was the tenth +/- 1 (range 8-13) after
      Epirubicin. The minimum required target for one high-dose procedure was collected
      in a single leukapheresis in 13 patients. Moreover, in 9 cases one procedure was
      adequate for two high-dose courses (i.e. > or = 10 x 10(6)/kg/bw CD34+ cells).
      Response to Epirubicin was evaluable in 14/20 cases, with a response rate of 50%.
      CONCLUSIONS: Epirubicin delivered at 150 mg/sqm is a very effective mobilising
      agent for breast cancer patients; to ameliorate the response rate other active
      drug(s) should be added.

PMID- 8750159
TI  - Intermittent continuous infusion of ifosfamide and 5-fluorouracil in patients
      with advanced adenocarcinoma of the pancreas.
AB  - BACKGROUND: In advanced adenocarcinoma of the pancreas treatment with 5
      fluorouracil (5-FU) or ifosfamide results in response rates of approximately 20%.
      Continuous infusion of these drugs is on many grounds theoretically attractive
      and may therefore offer advantages over bolus or short-term infusion. PATIENTS
      AND METHODS: Sixteen patients with advanced adenocarcinoma of the pancreas with
      progressive measurable disease and no previous chemotherapy entered the study.
      After implantation of a subcutaneous infusion chamber patients were treated on
      days 1-12 with ifosfamide (1.0 g/m2/day) and 5-FU (300 mg/m2/day) as a continuous
      intravenous infusion using a portable infusion pump. Mesna (1.0 g/m2/day) was
      added as uroprotective agent from day 1-14. Courses were repeated every 4 weeks.
      RESULTS: Fifteen of the 16 patients were evaluable for response. One partial
      response was observed (response rate 7% [95% CI: 0%-32%]). Toxicity occurred in
      64% of the courses. Dose limiting toxic effects were grade 3 nausea/vomiting
      (WHO) in 3 patients, grade 2 mucositis in 1 patient and grade 4 leukopenia in 1
      patient. CONCLUSION: Intermittent continuous infusion with ifosfamide, mesna and
      5-FU is feasible on an outpatient basis. Although continuous infusion of
      ifosfamide may have a more favorable toxicity profile, the combination of 5-FU
      and ifosfamide in this schedule is no more effective than bolus or short-term
      infusion.

PMID- 8750160
TI  - Hepatitis C virus infection and autoimmune thrombocytopenic purpura.
AB  - BACKGROUND/AIMS: Chronic hepatitis C virus infections are often associated with
      extra-hepatic immunological manifestations, including various autoimmune
      disorders. The aims of this study were: (i) to determine the prevalence of
      hepatitis C virus markers in patients with autoimmune thrombocytopenic purpura,
      and (ii) to determine whether a relationship could exist between autoimmune
      thrombocytopenic purpura and hepatitis C virus infections. METHODS: One hundred
      and thirty-nine patients with autoimmune thrombocytopenic purpura (45 men, 94
      women, mean age 42 years, range 16-90) were studied. RESULTS: Anti-HCV antibodies
      were sought in their first and last available cryopreserved sera. In case of
      seropositivity, all their available cryopreserved sera were tested for anti-HCV
      antibodies and for HCV-RNA. Anti-HCV antibodies were detected in 14 of the 139
      patients (10%). Four patients had transient anti-HCV seropositivity due to
      passive transfer of anti-HCV antibodies secondary to the infusion of intravenous
      immunoglobulin concentrates. Three patients seroconverted during follow up, due
      to intravenous drug use in one case, transfusion of non-HCV-screened blood units
      in one case, and infusion of intravenous immunoglobulins in one case. Seven
      patients had chronic hepatitis C discovered at the same time as autoimmune
      thrombocytopenic purpura. In two of them, hepatitis C virus transmission was the
      consequence of autoimmune thrombocytopenic purpura treatment but, in five cases,
      hepatitis C virus infection predated autoimmune thrombocytopenic purpura, so that
      the role of hepatitis C virus in autoimmune thrombocytopenic purpura could be
      suggested. CONCLUSIONS: Whereas hepatitis C virus does not appear to be the main
      etiological agent of autoimmune thrombocytopenic purpura can be envisaged. On the
      other hand, treatment of autoimmune thrombocytopenic purpura or autoimmune
      thrombocytopenic purpura-related symptoms by blood product infusion can be
      complicated by hepatitis C virus transmission.

PMID- 8750161
TI  - Hepatitis C virus-specific B cell activation: IgG and IgM detection in acute and
      chronic hepatitis C.
AB  - BACKGROUND/AIMS/METHODS: Immunological responses to hepatitis C virus infection
      have not been fully studied. In an attempt to clarify some immunopathogenetic
      aspects of B cell activation during acute and chronic hepatitis C virus infection
      and to identify markers of chronicity or of recovery, the humoral response in
      hepatitis C virus-infected patients was studied. RESULTS: In children with acute
      jaundice, with negative markers of acute hepatitis A, B and E, six of 87 (6.9%)
      had detectable anti-HCV IgM, and only one (1.1%) had detectable anti-HCV IgG. In
      adults with acute jaundice, with negative markers of acute hepatitis A, B and E,
      ten of 23 (43.5%) had detectable anti-HCV IgM associated in eight patients with
      detectable anti-HCV IgG. In chronic hepatitis C virus-infected adult patients,
      all anti-HCV IgG seropositive, four of 14 (28%) patients had detectable HCV-IgM
      in serum. In vitro specific antibody production was inducible in a minority of
      patients. In acute and chronic hepatitis C virus-infection, IgM-HCV serology did
      not correlate with viremia as detected by polymerase chain reaction. CONCLUSIONS:
      Therefore, the polymerase chain reaction remains at the moment the only direct
      marker to demonstrate hepatitis C virus viral replication in patients with acute
      and chronic hepatitis while anti-HCV IgM analysis alone has only a limited
      diagnostic value in hepatitis C virus-infection.

PMID- 8750162
TI  - Genotype, slow decrease in virus titer during interferon treatment and high
      degree of sequence variability of hypervariable region are indicative of poor
      response to interferon treatment in patients with chronic hepatitis type C.
AB  - In a study assessing factors associated with a good or a poor response to
      interferon treatment in patients with chronic hepatitis type C, we analyzed serum
      samples taken from 26 interferon-treated patients and found further evidence that
      infection with genotype II is associated with a poor response. Whereas all seven
      patients with group III genotype tested showed a good response (normalization of
      alanine aminotransferase level for more than 6 months), only 10 of 19 (53%)
      patients infected with group II genotype showed a good response. We also observed
      that 16 of 17 (94%) patients who exhibited a rapid virus titer decrease during
      the first 2 weeks of treatment later showed a good response. In contrast, only
      three of nine (33%) patients with an initially slow viral decrease eventually
      showed a good response (p<0.04). None of the 26 control patients exhibited a
      marked virus decrease or normalization of serum alanine aminotransferase level.
      Interestingly, high degrees of sequence variability were seen in three patients
      with group II hepatitis C virus who responded poorly to the therapy. All three
      showed slow decreases in virus titer during the first 2 weeks of treatment. In
      contrast, patients with genotype II who showed a good response to treatment were
      seen to have very few mutations. In three patients with genotype III who had
      responded well to interferon treatment, all showed very little amino acid
      sequence variability in the hypervariable region compared with patients with
      genotype II who had responded poorly to interferon treatment. These data suggest
      that a slow decrease in virus titer during the beginning of interferon treatment
      and a high degree of sequence variability, both of which are often seen in
      patients with group II genotype, are associated with poor response to interferon
      treatment.

PMID- 8750163
TI  - Evaluation of a reverse hybridization assay for genotyping of hepatitis C virus.
AB  - BACKGROUND/AIMS: Several strains of the hepatitis C virus exist; distinct
      genotypes and subtypes can be identified by sequence comparison of the viral
      genomes. Recent evidence that the genotype/subtype of hepatitis C virus may
      influence the clinical course of chronic hepatitis C and the response to
      interferon-alpha therapy for this disease suggests that methods to identify the
      genotype may become clinically useful. In the present study we evaluated a
      recently introduced reverse hybridization assay. METHODS: HCV-RNA was isolated
      from serum samples from 61 consecutive patients attending our out-patient clinic
      and subsequently sequenced in the 5'-noncoding and the nonstructural-5 region by
      the dideoxynucleotide chain termination method. HCV-genotyping was performed by
      phylogenetic analysis of nonstructural-5 sequences. The amplification product for
      the reverse hybridization assay was obtained by "nested" polymerase chain
      reaction using biotinylated primers corresponding to the 5'-noncoding region. The
      assay is based on hybridization of the resulting polymerase chain reaction
      product with oligonucleotide probes immobilized as parallel lines on membrane
      strips. RESULTS: According to the phylogenetic analysis of the nonstructural-5
      region the prevalence of hepatitis C virus subtypes was as follows: 1a 18%, 1b
      51%, 2a 3%, 2b 3%, 2c 7% and 3a 18%. The reverse hybridization assay correctly
      identified each hepatitis C virus genotype (1, 2, and 3). However,
      differentiation of hepatitis C virus subtypes was insufficient. 1/11 HCV-1a
      isolates was incorrectly classified by the reverse hybridization assay as HCV-1b
      and vice versa 3/31 HCV-1b isolates as HCV-1a. Classification of hepatitis C
      virus subtypes 2a, 2b and 3a was correct, but 4/4 HCV-2c isolates were
      misinterpreted by the assay as HCV-2a. CONCLUSIONS: The reverse hybridization
      assay can differentiate between hepatitis C virus genotypes 1, 2, and 3, but is
      not completely reliable for hepatitis C virus subtyping.

PMID- 8750164
TI  - Survival and complications in a cohort of patients with anti-delta positive liver
      disease presenting in a tertiary referral clinic.
AB  - BACKGROUND/AIMS: Our aim was to evaluate the clinical outcome and survival of
      patients with anti-Delta positive liver disease in The Netherlands. METHODS: We
      evaluated those patients visiting our hospital between 1978 and 1993 with respect
      to clinical, virological and histological parameters. During the follow-up period
      the occurrence of complications of the liver disease and survival was determined.
      Thirty patients with a median age of 34 years (range 21-52) were included.
      RESULTS: During an average follow up of 4.8 years, nine patients died. The
      overall 5-year survival as estimated by Kaplan-Meyer analysis was 71%, which was
      comparable to hepatitis B cirrhosis patients. However, in the group without
      active hepatitis B replication (HBeAg-negative) a clear trend towards a worse
      survival was identified in Delta cirrhosis patients. Complications and deaths
      occurred exclusively in the patient group with cirrhotic liver disease. The
      complications (ascites, elevated bilirubin >34 micro mol/l), variceal bleeding
      and spontaneous bacterial peritonitis) occurred in 52% of the patients with a
      follow up of more than 6 months (n=27). Fifty-seven percent of those patients
      died. In our population anti-Delta positive liver disease affects predominantly
      young patients and is related to advanced liver disease. CONCLUSIONS: In view of
      the high death rate, liver transplantation should be considered when signs or
      symptoms of decompensated liver disease occur.

PMID- 8750165
TI  - Hepatitis E virus infection in a cohort of patients with acute non-A, non-B
      hepatitis.
AB  - BACKGROUND/AIMS: The aim of this study was to determine the frequency of
      hepatitis E virus infection in a cohort of patients with acute non-A, non-B
      hepatitis in Greece. METHODS: Serial serum samples of 198 patients with acute non
      A, non-B hepatitis and a single serum specimen from 316 healthy subjects were
      tested for IgG and IgM antibodies to hepatitis E virus (anti-HEV). RESULTS: Anti
      HEV IgG was found in 15/198 (7.6%) of acute non-A, non-B hepatitis patients and
      7/316 (2.2%) of healthy controls (p=0.007). Anti-HEV IgM was found in 2/198
      (1.0%) acute non-A, non-B hepatitis patients and in none of the healthy subjects.
      Neither anti-HEV IgM (+) case reported any risk factor and neither had travelled
      in areas endemic for hepatitis E virus infection. HEV-RNA was detected by reverse
      transcription polymerase chain reaction in one patient. The prevalence of anti
      HEV IgG was 7/45 (15.6%), 1/46 (2.2%), 5/30 (16.7%) and 2/77 (2.6%) in acute non
      A, non-B hepatitis reporting transfusion, intravenous drug use,
      occupational/hospitalization, and unknown transmission, respectively (p=0.007).
      Anti-HEV IgG was found in 13/122 (10.7%) and 2/76 (2.6%) of acute non-A, non-B
      hepatitis patients positive and negative for anti-HCV, respectively (p=0.03). A
      similar association was found with anti-HBc (p=0.007). The prevalence of anti-HEV
      IgG was significantly higher in cases reporting transfusion [OR=7.3, 95% C.I. 1.4
      37.7, p=0.017] and occupational/hospitalization [OR=6.8, 95% C.I. 1.2-38.2,
      p=0.029], as transmission category after controlling for age. CONCLUSIONS: These
      findings indicate that: (a) hepatitis E virus may be a cause - although not a
      frequent one - of sporadic or community-acquired acute non-A, non-B hepatitis in
      Greece; (b) hepatitis E virus may share transmission routes with hepatitis B and
      C viruses; and (c) the hypothesis that hepatitis E virus may be transmitted by
      parenteral routes deserves careful consideration.

PMID- 8750166
TI  - Kinetics of anti-M2 antibodies after liver transplantation for primary biliary
      cirrhosis.
AB  - BACKGROUND/AIMS: Orthotopic liver transplantation is currently considered as the
      treatment of choice for primary biliary cirrhosis in the terminal stage and, as
      for other autoimmune liver disease, the risk of recurrence of the disease within
      the graft has been raised. There is, however, some discrepancy about the risk of
      recurrence based on pathological analysis. In addition, pathological recurrence
      of primary biliary cirrhosis within the graft is not always associated with a
      rise in the serological markers of the disease. In order to clarify this
      situation, we have monitored antimitochondrial antibodies before and after
      transplantation. METHODS: Antimitochondrial antibodies were detected by indirect
      immunofluorescence (variation in antibody titers) and the antimitochondrial
      antibodies-2 by western blotting (variation in the number of peptides recognized
      in 16 primary biliary cirrhosis patients followed for at least 4 years after
      transplantation. RESULTS: Antimitochondrial antibody titers had normalized 1 year
      after transplantation in seven patients, declined in seven others and remained
      unchanged in two. Over the 4 years of follow up, four patients demonstrated a
      subsequent increase in antimitochondrial antibody titers. Western blot analysis
      demonstrated the loss of one or more bands in seven patients during the first
      operative year after transplantation and in three other patients thereafter; in
      six patients the western blotting profile remained identical to that obtained
      before transplantation. The important changes generally occurred during the first
      year post-transplantation, without significant changes thereafter, except for
      three patients who demonstrated a secondary reappearance of the initially lost
      band. Disappearance of all bands was never observed. There was no concordance
      between the normalization of antimitochondrial antibody titers (indirect
      immunofluorescence) and the reduction in the number of peptides recognized
      (western blotting). Serum bilirubin and alkaline phosphatase levels had
      normalized by 1 year after transplantation, and remained normal thereafter.
      Routine liver biopsies performed on a yearly basis did not disclose any pattern
      suggestive of primary biliary cirrhosis recurrence. CONCLUSIONS:
      Antimitochondrial antibody titers decreased in primary biliary cirrhosis patients
      after liver transplantation, although antimitochondrial antibodies-2 never
      disappeared as assessed by western blotting. In the present study these features
      were not associated with biochemical or histological (correction of
      histoclogical) evidence of primary biliary cirrhosis recurrence.

PMID- 8750167
TI  - Plasma endothelin levels in patients with cirrhosis and their relationships to
      the severity of cirrhosis and renal function.
AB  - BACKGROUND/AIMS: Increased plasma endothelin levels have been reported in
      patients with cirrhosis. However, the relationship between plasma endothelin
      concentrations and hyperdynamic circulation or renal functions has not been
      documented. METHODS: We measured the plasma endothelin-1 and endothelin-3
      concentrations using radioimmunoassay in 96 patients with cirrhosis (Pugh's A in
      26, Pugh's B in 45 and Pugh's C in 25) and compared these values to 56 age- and
      sex-matched healthy subjects. Systemic and portal hemodynamic measurements,
      effective renal plasma flow, creatinine clearance, plasma aldosterone
      concentration and plasma renin activity were recorded for each patient. RESULTS:
      Plasma endothelin-1 and endothelin-3 levels were significantly increased in
      patients with cirrhosis compared to healthy subjects. Additionally, plasma
      endothelin-1 and endothelin-3 values were higher in patients with cirrhosis and
      ascites than in those without ascites. Moreover, plasma endothelin-1 levels
      increased in relation to the severity of cirrhosis. On the other hand, modest
      negative correlations were found between endothelin-1 and creatinine clearance or
      effective renal plasma flow. CONCLUSIONS: Plasma endothelin-1 and endothelin-3
      levels are increased in patients with cirrhosis compared to healthy subjects. The
      increase in plasma endothelin-1 levels is related at least in part to the
      severity of cirrhosis. Increased endothelin-1 levels may possibly contribute to
      renal dysfunction in patients with cirrhosis.

PMID- 8750168
TI  - Weakness of mucosal barrier in portal hypertensive gastropathy of alcoholic
      cirrhosis. Effects of propranolol and enprostil.
AB  - BACKGROUND/AIMS: It has been suggested that the vulnerability of gastric mucosa
      is increased in patients with cirrhosis as a result of a PGE2 deficiency.
      Therefore, we evaluated whether PGE2 mucosal generation, and gastric potential
      difference - a reflection of the gastric mucosal barrier - were correlated to
      endoscopic features and whether these alterations could be alleviated. METHODS:
      The potential difference was measured before (basal) and after a stimulation test
      by aspirin. The serum levels of gastrin and glucagon were also determined.
      Finally, the effects of a 1-week administration of propranolol or enprostil were
      tested on potential difference. The endoscopic grade of portal hypertensive
      gastropathy was assessed according to McCormack et al. The results are presented
      respectively for controls, patients with mild gastropathy, and patients with
      severe gastropathy. Comparisons were made using variance or covariance analysis
      after adjustment with age. RESULTS: Basal potential difference was significantly
      different between the three groups: -30.6, -28.8, -24.9 mV, p <0.05,
      respectively. The effects of aspirin administration on potential difference
      parameters were significantly different between the three groups (irritability
      index: 35 +/- 25, 92 +/- 98, 114 +/- 74 mV2.min, p <0.05, respectively) when non
      responders to aspirin were excluded. PGE2 mucosal generation was significantly
      increased in both the antrum (9.8, 19.5, 19.7 ng/mg proteins, p<0.05,
      respectively) and in the corpus (8.1, 14.0, 20.2 ng/mg proteins, p<0.05,
      respectively). PGE2 generation was not related to potential difference. Glucagon
      serum levels were related to the grade of gastropathy. A 1-week administration of
      160 mg/d long-acting propranolol, 35 micro g/d enprostil or placebo did not
      significantly modify basal potential difference. CONCLUSIONS: Portal hypertensive
      gastropathy is characterized by a decreased potential difference proportional to
      the endoscopic severity. The gastric mucosa of patients with cirrhosis seems to
      be more susceptible to aspirin than that of healthy subjects. It appears that the
      role of PGE2 is controversial in portal hypertensive gastropathy. Propranolol and
      enprostil do not improve this decreased potential difference.

PMID- 8750169
TI  - A prospective evaluation of changes in neuropsychological and liver function
      tests following transjugular intrahepatic portosystemic stent-shunt.
AB  - BACKGROUND/AIMS: This study was designed to assess changes in: (a)
      neuropsychological tests, measures of memory, quality of life and scores for
      anxiety and depression; (b) liver function tests; and (c) the relationship
      between these following transjugular intrahepatic portosystemic stent-shunt.
      METHODS: Twenty-nine patients undergoing transjugular intrahepatic portosystemic
      stent-shunt for recurrent variceal haemorrhage, 12 matched patients with
      cirrhosis and variceal haemorrhage managed with variceal band ligation and 16
      normal controls were studied. Patients in any of the groups who were clinically
      encephalopathic were excluded from the study. Serial changes in the conventional
      liver function tests and Indocyanine green clearance, and psychometric function
      (Hospital Anxiety Depression Scale, Rivermead Behavioral Memory Test, Quality of
      Life and the memory and reaction sub-tests of the Cambridge Automated
      Neuropsychological Test Assessment Battery) were measured prior to and 1, 3, 9
      and 15 months following transjugular intrahepatic porto-systemic stent-shunt.
      RESULTS: Over a mean follow up of 9.1 months in the transjugular intrahepatic
      portosystemic stent-shunt group (range 3-28), one patient (3%) developed
      clinically detectable encephalopathy. Sixty-seven percent of patients with
      cirrhosis showed evidence of subclinical encephalopathy as compared with the
      control population. Significant deterioration occurred in the reaction sub-tests
      of the Cambridge Automated Neuropsychological Test Assessment Battery in
      patients, both in the transjugular intrahepatic portosystemic stent-shunt group
      and the controls with cirrhosis, during follow up. Transjugular intrahepatic
      portosystemic stent-shunt was followed by significant deterioration in levels of
      anxiety and psychological component of the quality of life. The Rivermead
      Behavioural Memory Test and the memory sub-test of the Cambridge Automated
      Neuropsychological Test Assessment Battery did, however, improve significantly at
      1 and 15 months after transjugular intrahepatic portosystemic stent-shunt,
      respectively. Serum alanine aminotransferase, bilirubin and indocyanine green
      clearance deteriorated significantly following transjugular intrahepatic
      portosystemic stent-shunt (p <0.001, p <0.001 and p <0.0001, respectively).
      Significant correlation was observed between changes in the indocyanine green
      clearance and changes in the complex and simple reaction time subtests of the
      Cambridge Automated Neuropsychological Test Assessment Battery (r = 0.6 and r =
      0.66, respectively). CONCLUSIONS: The results of this study showed that about 67%
      of patients with cirrhosis were subclinically encephalopathic and that temporary
      deterioration occurred in the Cambridge Automated Neuropsychological Test
      Assessment Battery during follow up, both in patients having transjugular
      intrahepatic portosystemic stent-shunt and in the controls with cirrhosis. These
      parallel the changes in the liver function tests and indocyanine green clearance.
      Temporary deterioration was also observed in the Quality of Life and Hospital
      Anxiety Depression Scale in the transjugular intrahepatic portosystemic stent
      shunt group, although the measures of memory improved. Further studies should
      address the biochemical mechanisms of these changes and the role of prophylactic
      measures.

PMID- 8750170
TI  - Elevated levels of serum carbohydrate deficient transferrin are not specific for
      alcohol abuse in patients with liver disease.
AB  - BACKGROUND: Serum carbohydrate deficient transferrin is a marker of chronic
      alcohol consumption; it increases above normal in healthy individuals after a
      daily alcohol intake of more than 60 g/d for more than 2 weeks. The influence of
      liver disease itself on carbohydrate deficient transferrin levels has not been
      sufficiently established. METHODS: We investigated serum levels of carbohydrate
      deficient transferrin in 196 consecutive patients admitted to our
      Gastroenterology and Hepatology Unit and correlated this parameter with the
      patients' statements about alcohol intake during the previous 2 weeks and with
      other markers of chronic alcohol consumption. RESULTS: In our patient population,
      carbohydrate deficient transferrin had the best overall performance with respect
      to sensitivity (88%), specificity (82%), and negative predictive value (98%), as
      compared to other markers, although specificity was much lower than previously
      reported in patients without liver disease. In the group of patients with liver
      disease, sensitivity and specificity were 90% and 73%, respectively, and in
      patients without liver disease, 80% and 88%. The negative predictive value was
      excellent (96% for patients with liver disease and 99% for patients without liver
      disease). CONCLUSIONS: Thus, in a patient with a negative interview for chronic
      alcohol abuse and normal carbohydrate deficient transferrin level, alcohol is
      unlikely to be the cause of liver disease, and further investigations to
      establish the etiology of liver disease are warranted. An increased carbohydrate
      deficient transferrin level, however, cannot be regarded as reliable evidence for
      chronic alcohol abuse in patients with liver disease.

PMID- 8750171
TI  - Tamoxifen inhibits hepatoma cell growth through an estrogen receptor independent
      mechanism.
AB  - BACKGROUND/AIMS: Tamoxifen has previously been shown to prolong the survival of
      patients with advanced stages of hepatocellular carcinoma and it has been
      suggested that it inhibits the growth of hepatoma cells through an estrogen
      receptor-dependent mechanism. We have studied the effects of the synthetic
      estrogen, mestranol, and the antiestrogen, tamoxifen, on the growth regulation of
      hepatoma cells in vitro. METHODS: Cells were maintained under fully estrogenized
      conditions and were deprived of estrogen shortly before conducting experiments.
      RESULTS: In the human hepatoma cell line Hep 3B, tamoxifen inhibited cell growth
      in a concentration and time-dependent manner with effective concentrations
      ranging from 0.1 microM to 10 microM. Mestranol inhibited cell growth at a
      concentration of 10 microM and had an additive effect with tamoxifen on growth
      inhibition. Expression of estrogen receptors in hepatoma cells was not detected
      by enzyme immunoassay, Northern blot analysis or reporter gene expression assay.
      Furthermore, the introduction of estrogen receptors into Hep 3B cells did not
      alter the effect of tamoxifen and mestranol on cell growth. CONCLUSIONS: This
      study suggests that tamoxifen inhibits the growth of Hep 3B hepatoma cells
      through an estrogen receptor-independent mechanism.

PMID- 8750172
TI  - Protective properties of amino acids in liver preservation: effects of glycine
      and a combination of amino acids on anaerobic metabolism and energetics.
AB  - BACKGROUND/AIMS/METHODS: In this study, we investigated the hepatoprotective
      effects of three storage solutions containing glycine (180 mM), glycylglycine
      (180 mM), and a mixture of 20 amino acids (combined concentration of 180 mM) on
      energy metabolism and levels of glucose and lactate (as an index of glycolytic
      flux) in rat livers. All effects were compared to those of livers flushed/stored
      with a modified University of Wisconsin solution. RESULTS: Glycine-treatment
      showed no improvement in liver energetics (ATP, ADP, AMP) and lactate
      accumulation; this solution had the lowest buffering capacity of the four tested
      (approximately 30% of the University of Wisconsin solution). The glycylglycine
      solution had the highest buffering capacity of the four solutions tested
      (including University of Wisconsin solution). Complete titration of the glycine-,
      combined amino acids-, and University of Wisconsin solutions (from 8.0 to pH =
      6.0) resulted in a minor decrease in glycylglycine buffer pH; pH dropped by 0.2
      pH units. In glycylglycine-treated livers, energetics showed an improvement over
      the first 1 h cold storage; ATP and 'energy charge' values remained high and ADP
      levels (and consequently total adenylate contents) were 0.7-2.4 micro mol/g
      greater than livers stored in University of Wisconsin solution. A 2-fold increase
      in lactate accumulation suggested that the improvement in liver energetics for
      the glycylglycine buffer was due to maintained flux through glycolysis brought
      about by enhanced buffering capacity. The solution containing a combination of
      amino acids exhibited maximum maintenance of liver energetics via increased
      glycolytic flux, despite its slightly inferior buffering capacity (85% of
      University of Wisconsin solution). ATP levels were maintained over the first 2 h
      storage and ADP levels (and consequently, total adenylate contents) were 1.2-2.1
      micro mol/g greater than University of Wisconsin solution-treated livers during
      the entire 24 h storage period. Energy charge values for livers treated with the
      combination of amino acids were also significantly higher than with glycine-,
      glycylglycine- and University of Wisconsin solution-treatment; even at 24 h,
      energy charge was 0.36 (comparable to only 4 h storage in University of Wisconsin
      solution). CONCLUSIONS: Our data suggest that a combination of amino acids may be
      required for maximum protection of the liver, and furthermore there may be
      several independent mechanisms, including buffering capacity, responsible for
      cytoprotection of the liver during cold storage.

PMID- 8750173
TI  - Reticuloendothelial system function in acute liver injury induced by D
      galactosamine.
AB  - AIMS/METHODS: Reticuloendothelial system function, as assessed by clearance of
      radiolabelled bacteria, was evaluated in acute liver injury induced by D
      galactosamine in rats, and compared with that after 70% liver resection model.
      RESULTS: Reticuloendothelial system function was significantly impaired in both
      instances, but the extent and the pattern of reticuloendothelial system
      impairment differed in the two models. While the elimination rate of the
      radiolabelled bacteria (k-value) decreased in both the liver resection and D
      galactosamine groups (19% and 52%, respectively), the corrected phagocytic index
      (alpha) increased in 70% liver resection (247%), indicatine increased activity
      among the remaining reticuloendothelial system cells of the liver. Estimation of
      subserosal organ blood flow showed decreased flow to the cecum and distal small
      intestine (correction of intesting) in both groups, whereas it was significantly
      increased (477%) in the remaining parts of the liver in the liver resection
      group. CONCLUSIONS: These findings show that reticuloendothelial system activity
      is deranged in both these groups, which may explain the increased occurrence of
      bacterial complications observed in corresponding clinical conditions.

PMID- 8750174
TI  - Recurrent episodes of acute hepatitis associated with LKM-1 (cytochrome P450 2D6)
      antibodies in identical twin brothers.
AB  - BACKGROUND/AIMS: Liver/kidney microsomal antibodies have been noted in liver
      disease of different etiology, e.g. in autoimmune hepatitis, chronic hepatitis C
      and D virus infection and in drug-induced liver disease. Unlike these, acute
      hepatitis of unknown etiology associated with high-titer liver/kidney microsomal
      1 antibodies (cytochrome P450 2D6) is reported in identical twin brothers.
      METHODS: Patients were studied using clinical, biochemical, serological and
      immunological methods, as well as liver biopsy. RESULTS: The acute icteric
      episodes were followed by spontaneous remission with complete normalization of
      liver function tests and liver histology. During the acute phase, serum titer for
      liver/kidney microsomal-1 antibodies (detected by indirect immunofluorescence,
      ELISA and Western blot analysis) was exceedingly high and decreased gradually
      thereafter. Hepatitis C and D virus infection were excluded by repeated
      serological testing; exposure to drugs or chemicals was not evident. Concomitant
      autoimmune disease was not detectable. HLA typing for class 1 and 2 antigens was
      positive for the HLA haplotype DQ2, but negative for HLA B4, B8, DR3 and DR4.
      CONCLUSIONS: The present observations might suggest a hitherto unreported form of
      acute hepatitis of unknown etiology, distinct from other liver diseases in which
      liver/kidney microsomal antibodies have been described so far.

PMID- 8750175
TI  - Complete response to interferon-alpha for acute hepatitis C after needlestick
      injury in a hemodialysis nurse.

PMID- 8750176
TI  - Simple fluorescent enzyme immunoassay for detection and quantification of
      hepatitis C viremia.
AB  - The viral load of hepatitis C virus, as reflected by hepatitis C virus viremia,
      has been shown to have important clinical implications. In this study the
      hepatitis C virus core protein level in serum was evaluated for the detection and
      quantification of hepatitis C virus viremia. Hepatitis C virus core protein in
      serum was detected using a simple and sensitive fluorescent enzyme immunoassay.
      Hepatitis C virus core protein was quantitated in 100 healthy subjects, 258
      patients with hepatitis C virus infection and 108 patients with non-hepatitis-C
      virus-related chronic liver diseases. HCV-RNA was determined using the branched
      DNA (bDNA) assay and reverse-transcription polymerase chain reaction. The
      detection limit of this fluorescent enzyme immunoassay was found between 10(4) -
      10(5) copies/ml HCV-RNA equivalent. There was a good correlation between the core
      protein and bDNA assay results (p <0.01). Hepatitis C virus core protein was
      detected in 81% of patients with hepatitis C virus infection (acute hepatitis
      4/5, chronic hepatitis 85/104, cirrhosis 64/73 and hepatocellular carcinoma
      56/76) but in none of the healthy subjects and patients with non-hepatitis C
      virus chronic liver diseases. The amount of hepatitis C virus core protein in
      patients with hepatitis-C-virus-related hepatocellular carcinoma was lower
      compared to chronic hepatitis and cirrhosis (p <0.05). All 26 patients treated
      with interferon-alpha showed parallel changes between HCV-RNA and core protein
      levels. This fluorescent enzyme immunoassay is simple and quick (assay time <3 h)
      with sensitivity at least matching the bDNA assay. Similar levels of hepatitis C
      virus core protein were detected in patients with chronic hepatitis and
      cirrhosis, but patients with hepatocellular carcinoma tended to have a lower
      level of hepatitis C virus core protein.

PMID- 8750177
TI  - Liver-directed gene therapy: molecular tools and current preclinical and clinical
      studies.

PMID- 8750178
TI  - Cholestatic hepatitis related to quinolones: a report of two cases.

PMID- 8750179
TI  - Are basal core-IgM antibodies to hepatitis C virus predictive of successful alpha
      interferon therapy?

PMID- 8750180
TI  - Is alpha-interferon treatment useful in children with non-B, non-C chronic
      hepatitis?

PMID- 8750181
TI  - Severe cholestasis and sicca syndrome after thiabendazole.

PMID- 8750182
TI  - Expression of variant CD44 epitopes in human astrocytic brain tumors.
AB  - Expression of CD44 and of specific splice-variants of CD44 has been causally
      related to metastatic behaviour in a variety of carcinomas and lymphomas. To
      elucidate whether, in principle, similar splice-variants could be involved in
      glioma cell invasion we examined the expression of CD44 and its splice-variants
      in a series of 38 primary human brain tumors (28 astrocytomas, WHO grade I-III
      and 10 glioblastomas, WHO grade IV) and in cell lines derived from 9
      glioblastomas. All brain tumors examined showed strong immunoreactivity for an N
      terminal epitope present on all CD44 isoforms known. Using a polyclonal antiserum
      raised against the complete sequence encoded by variant exons v3 to v10, CD44
      splice-variants could be detected irrespective of the grade of malignancy in many
      of the tumor samples at a low level and often restricted to only a few clustered
      tumor cells. Thus, the N-terminal epitope probably indicates the presence of the
      smallest and most ubiquitous isoform CD44s. Interestingly, all glioblastomas
      expressed CD44 variants whereas expression in astrocytomas WHO grade I, II, and
      III could only be detected in about half of the tumor samples. Using reverse
      transcriptase-PCR we were able to detect different CD44 splice-variants in the
      glioblastoma cell lines and in cultured primary astrocytic cells. Glioblastoma
      cells analyzed by flow cytometry showed the expected binding capacity for
      hyaluronic acid which could be increased twofold after pretreatment with
      hyaluronidase. The results presented show that there is low expression of CD44
      variants in human tumors of astrocytic origin. Expression of CD44 and its splice
      variants could contribute to the migration capacity of neoplastic astrocytes, and
      may be considered as a target for new diagnostic and therapeutic approaches in
      the clinical management of brain tumors.

PMID- 8750183
TI  - Schwann cell tumors express characteristic patterns of CD44 splice variants.
AB  - Members of the CD44 family of cell surface hyaluronate-binding proteins have been
      implicated in cell migration, cell-matrix interactions and tumor progression. To
      determine whether these proteins might play a role in the normal functions of
      Schwann cells and in their tumorigenesis, we examined the patterns of CD44
      expression in Schwann cells from rat peripheral nerve, rat Schwann cell tumor
      lines, and human schwannomas. Normal rat spinal nerves and primary Schwann cell
      cultures expressed standard CD44 (CD44s) but not alternatively spliced variant
      isoforms. In contrast, rat Schwann cell tumor lines expressed both CD44s and a
      number of variants, including proteins containing sequences encoded by exon v6.
      Furthermore, we found that these cell lines bind hyaluronate, and that their cell
      surface hyaluronate binding correlates with CD44 expression. All of the human
      schwannomas also expressed CD44 variants, especially epitopes encoded by exon v5,
      the border between v7 and v8, and v9-10. These data indicate that Schwann cells
      normally express CD44s, that Schwann cell tumors express both CD44s and
      particular variants of CD44, and that CD44s and possibly variants of CD44 are
      involved in hyaluronate recognition by Schwann cell tumors.

PMID- 8750184
TI  - Expression of CD44 splice variants in human primary brain tumors.
AB  - Expression of CD44, particularly of certain splice variants, has been linked to
      tumor progression and metastatic potential in a number of different animal and
      human cancers. Although differential expression of CD44 standard epitopes (CD44s)
      in human brain tumors has been reported, the expression of CD44 variant exon
      encoded sequences (CD44v) in primary brain tumors in situ has not been studied in
      detail. In the present study, the expression of CD44s and CD44v epitopes was
      analyzed immunohistochemically on frozen sections of primary brain tumors. In
      addition, the expression of CD44 on cultured glioma cells was investigated by
      immunofluorescence flow cytometry. The results demonstrate the presence of CD44s
      epitopes and of CD44 splice variants containing CD44v4, v5 and v10 sequences in
      various types of brain tumors. A subgroup of highly malignant gliomas showed a
      strong (focal) expression of CD44v5. CD44v6 was absent in all brain tumors
      examined. CD44s appeared to be the dominant form of CD44 expressed in primary
      brain tumors, its expression was not correlated with tumor grade. We envisage
      that CD44 isoforms, in particular CD44s, may contribute to the invasive character
      of primary tumors by interacting with hyaluronate, one of the most abundant
      molecules in the extracellular matrix of the brain.

PMID- 8750185
TI  - Expression of the CD44 adhesion molecule in tumours of the central and peripheral
      nervous system.

PMID- 8750186
TI  - Involvement of CD44 and its variant isoforms in membrane-cytoskeleton
      interaction, cell adhesion and tumor metastasis.
AB  - CD44s (standard form of CD44) is a transmembrane glycoprotein whose external
      domain displays extracellular matrix adhesion properties by binding both
      hyaluronic acid (HA) and collagen. The cytoplasmic domain of CD44s interacts with
      the cytoskeleton by binding directly to ankyrin. It has been shown that post
      translational modifications, such as phosphorylation (by protein kinase C),
      acylation (by acyl-transferase) and GTP-binding enhanced CD44's interaction with
      cytoskeletal proteins. Most importantly, the interaction between CD44s and the
      cytoskeletal protein, ankyrin, is required for the modulation of CD44s cell
      surface expression and its adhesion function. Recently, a number of tumor cells
      and tissues have been shown to express CD44 variant (CD44v) isoforms. Using RT
      PCR and DNA sequence analyses, we have found that unique CD44 splice variant
      isoforms are expressed in both prostate and breast cancer cell lines and
      carcinomas. Most importantly intracellular ankyrin is preferentially accumulated
      underneath the patched/capped structures of CD44 variant isoform in both breast
      and prostate cancer cells attached to HA-coated plates. We propose that selective
      expression of CD44v isoforms unique for certain metastatic carcinomas and their
      interaction with the cytoskeleton may play a pivotal role in regulating tumor
      cell behavior during tumor development and metastasis.

PMID- 8750187
TI  - The clinical significance of malfunction of the CD44 locus in malignancy.

PMID- 8750188
TI  - Hyaluronan: RHAMM mediated cell locomotion and signaling in tumorigenesis.
AB  - Extracellular matrix molecules and their receptors are important regulators of
      cell movement, adhesion and cytoskeletal organization. Adhesion molecules can
      also serve to mediate signal transduction and can influence, and sometimes
      direct, the events required for tumorigenesis. The extracellular matrix molecule,
      hyaluronan and its receptors have been implicated in transformation and
      metastasis, in particular the processes of tumor cell motility and invasion.
      RHAMM (receptor for hyaluronan mediated motility) is required for the cell
      locomotion of ras-transformed fibrosarcoma cells, cytokine stimulated fibrobasts
      and T lymphocytes, malignant B cells, and breast carcinoma cells. HA:RHAMM
      interactions promote cell locomotion via a protein tyrosine kinase signal
      transduction pathway that targets focal adhesions. The tyrosine kinase pp60c-src
      is associated with RHAMM in cells and is required for RHAMM mediated cell
      motility. It is possible that a RHAMM/src pathway induces focal adhesions to
      signal the cytoskeletal changes required for elevated cell motility seen in tumor
      progression, invasion and metastasis.

PMID- 8750189
TI  - Molecular mechanisms regulating the hyaluronan binding activity of the adhesion
      protein CD44.
AB  - In the present study, we describe the isolation and characterization of a cDNA
      clone designated B6F1.3, that appears to 'activate' the hyaluronan-binding
      capacity of CD44 upon transfection into the murine fibroblastoid cell line MOP8.
      Sequence analysis indicates that the putative regulatory molecule encoded by this
      clone is identical to the murine interleukin-2 receptor gamma chain (mIL-2R
      gamma), a recently described type 1 transmembrane protein that constitutes an
      integral component of the cell surface receptors that bind a number of cytokines
      including IL-2, IL-4, IL-7, IL-9, IL-15 and perhaps also IL-13. Mutations in this
      molecule have been shown to be responsible for X-linked severe combined
      immunodeficiency (XSCID) in humans. With the exception of bone marrow, the mIL-2R
      gamma chain was found to be expressed at high levels on all hemopoietic cell
      lines and tissue types examined. Non-hemopoietic tissues are generally negative.
      FACS analysis and Western blot analysis indicated respectively that B6F1.3 does
      not mediate its effects by upregulating the expression of CD44 or by altering the
      alternative splicing of the molecule. Removal of the cytoplasmic tail of the mIL
      2R gamma chain, including a Src homology region 2 (SH2) subdomain, abolished its
      ability to enhance CD44-mediated binding to hyaluronan suggesting the involvement
      of signal transduction events triggered via the cytoplasmic domain in the
      'activation' process. Determining whether activating molecules such as B6F1.3 are
      co-expressed within tumor cells may help improve the potential value of CD44 as a
      diagnostic marker of metastatic disease.

PMID- 8750190
TI  - Gene therapeutic approach to primary and metastatic brain tumors: I. CD44 variant
      pre-RNA alternative splicing as a CEPT control element.
AB  - Our laboratory and others have shown alternative splicing of up to ten exons at a
      discrete extracellular site to be primarily responsible for the generation of
      CD44 variant (CD44v) isoforms. Based on clear differences in the expression of
      these CD44v isoforms between normal and malignant tissues, we believe that
      elucidation of the mechanisms underlying the regulation of CD44 alternative
      splicing may provide a new gene therapeutic targeting approach based on CD44 pre
      mRNA processing in vivo. This strategy incorporates utilization of CD44
      alternative splicing control elements into a chimeric enzyme/prodrug therapy
      (CEPT), a novel modification of the virus-directed enzyme/prodrug therapy (VDEPT)
      approach for the treatment of brain metastases from tumors of systemic origin. As
      initial steps towards the development of a gene therapeutic approach based on
      targeting tumor cell expression of specific CD44v alternatively spliced isoforms,
      we have: (1) developed a novel in vivo assay system that allows the rapid
      analyses of potentially therapeutic CD44 alternative splicing minigene
      constructs; and (2) cloned the E. coli cytosine deaminase (CD) gene and fused its
      enzymatically active domain to alternatively spliced CD44 exons (CD44/CD).
      Deamination of cytosine by this CD44/CD chimeric fusion protein is demonstrated
      in E. coli cell lysates to be equal to that of wild type cytosine deaminase.

PMID- 8750191
TI  - Gene therapeutic approaches to primary and metastatic brain tumors: II. ribozyme
      mediated suppression of CD44 expression.
AB  - Glioblastomas are highly invasive intracerebral tumors that are known to express
      the CD44 cell adhesion molecule. Human glioma cell adhesion and invasion in vitro
      may in part be mediated by the interaction of CD44 with extracellular matrix
      proteins. To suppress the growth and invasive effects of CD44 expression on
      primary brain tumors we have designed two hammerhead ribozymes as potential gene
      therapeutic agents. Both ribozymes designed to target exon 2 of CD44 exhibited in
      vitro cleavage of in vitro transcribed CD44s and CD44R1 RNAs. The anti-CD44
      effect of these ribozymes results from directed RNA cleavage, requiring both a
      target sequence and an appropriate catalytic center. Further, following transient
      transfection of one of these ribozymes into the SNB-19 glioma cell line,
      significant in vivo cleavage activity against cellular CD44 transcripts was
      demonstrated by flow cytometrical analysis. These preliminary results suggest
      that CD44-directed hammerhead ribozymes may be useful as gene therapeutic agents.

PMID- 8750192
TI  - Molecular dissection of quantitative traits: progress and prospects.
AB  - QTL mapping is an increasingly useful approach to the study and manipulation of
      complex traits important in agriculture, evolution, and medicine. The molecular
      dissection of quantitative phenotypes, supplementing the principles of classical
      quantitative genetics, is accelerating progress in the manipulation of plant and
      animal genomes. A growing appreciation of the similarities among different
      organisms and the usefulness of comparative genetic information is making genome
      analysis more efficient, and providing new opportunities for using model systems
      to overcome the limitations of less-favorable systems. The expanding repertoire
      of techniques and information available for studying heredity is removing
      obstacles to the cloning of QTLs. Although QTL mapping alone is limited to a
      resolution of 0.1%-1.0% of a genome, use of QTL mapping in conjunction with a
      search for mapped candidate genes, with emerging technologies for isolation of
      genes expressed under conditions likely to account for the quantitative
      phenotype, and with ever more efficient megabase DNA manipulation and
      characterization bodes well for the prospect of isolating the genetic
      determinants of QTLs in the foreseeable future. In the words of Thoday (1961),
      "An extensive attack on quantitative genetics made from this point of view as
      well as the biometric approach should be a great help in answering questions
      concerning the nature of polygenes...."

PMID- 8750193
TI  - A radiation hybrid map of 40 loci for the distal long arm of human chromosome 8.
AB  - We generated a panel of 97 radiation hybrids from the cell line GM10156B, which
      contains only human chromosome 8 in a Chinese hamster ovary cell line background.
      Statistical analysis of the cosegregation of markers in the 97 radiation hybrids
      was used to construct a physical map delineating the order and intermarker
      distance of 40 8q24 loci. Twenty-one loci were ordered with maximum likelihood
      ratios greater than 1000:1. A high level of consistency was seen between our RH
      map and the published genetic map, suggesting that our panel will be a valuable
      resource for the rapid mapping of markers derived from human chromosome 8.

PMID- 8750194
TI  - An integrated map of human chromosome 6p23.
AB  - The human chromosomal band 6p23 is a Giemsa-negative (light) band that may be
      expected to be relatively gene rich. The genes for spinocerebellar ataxia type 1
      (SCA1), guanosine monophosphate reductase (GMPR), DEK involved in a subtype of
      acute myeloid leukemia (AML), and the folate-sensitive fragile site FRA6A, have
      already been mapped to 6p23. Recent linkage data have suggested evidence for a
      susceptibility locus for schizophrenia in the region. We have constructed a
      single YAC contig of approximately 100 clones spanning the entire 6p23 band from
      6p22.3 to 6p24.1 and covering 7.5-8.5 Mb of DNA. The YAC contig contains 55
      markers including genetically mapped STSs, physically mapped STSs, anonymous
      STSs, anonymous ESTs, and ESTs from the genes mapped to the region. The order of
      the genetically mapped STSs is consistent with their order in the contig and some
      of the markers not resolved on the genetic map have been resolved by the YACs.
      Four of the YACs from 6p23 and covering approximately 3 Mb of DNA have been used
      to isolate approximately 300 cosmids from a flow-sorted human chromosome 6 cosmid
      library, which have been organized into pockets. The proposed susceptibility
      locus for schizophrenia is most closely linked to D6S260, which is located within
      the YAC contig along with genetic markers < or = 5 cM on either side. Therefore,
      the presented materials are valuable reagents for characterization of the genomic
      region implicated in schizophrenia.

PMID- 8750195
TI  - Chromosomal localization and expressed sequence tag generation of clones from a
      normalized human adult thymus cDNA library.
AB  - Expressed sequence tags (ESTs) from 298 clones have been generated from a
      randomly primed, normalized human adult thymus cDNA library. We describe the
      chromosomal localization of 136 of these ESTs by PCR-based mapping to a human
      monochromosomal somatic cell hybrid panel. Data base similarities to known genes
      are also described. A subset (n = 18) of these randomly primed ESTs extended the
      sequence of ESTs from other tissues currently in dbEST. Of the nonrepetitive
      human adult thymus ESTs generated in this study, 237 (79.5%) have no similarity
      to current data base entries. This would suggest that our collection contains
      approximately 100 new coding regions from thymus tissue, a large proportion of
      which likely will represent the middle regions of genes. The mapped ESTs should
      prove useful as new gene-based markers for mapping and candidate gene hunting,
      particularly when anchored to a well-developed physical map of the human genome.

PMID- 8750196
TI  - Refined localization of the cerebral cavernous malformation gene (CCM1) to a 4-cM
      interval of chromosome 7q contained in a well-defined YAC contig.
AB  - Cerebral cavernous malformations (CCM) are vascular lesions present in some 20
      million people worldwide that are responsible for seizures, migraine, hemorrhage,
      and other neurologic problems. Familial cases ofCCM can be inherited as an
      autosomal dominant disorder with variable expression. A gene for CCM (CCM/)was
      recently mapped to a 33-cM segment of chromosome 7q in a large Hispanic family
      (Dubovsky et al.1995). Here, the collection of several new short tandem repeat
      polymorphisms (STRPs) within the region of interest on 7q and the refinement of
      the marker order in this region using both linkage analysis in CEPH families and
      especially YAC-based STS content mapping are described. Affected members of three
      Hispanic families share allele haplotypes indicating a common ancestral mutation
      within these families. Using the shared haplotype information along with analysis
      of crossovers in affected individuals from both the Hispanic and Caucasian
      families, the region likely to contain the CCMI gene has been reduced to a 4-cM
      segment of 7q between D7S2410 and D7S689. All markers within the refined
      chromosomal segment were located on a single YAC contig estimated to be
      approximately 2 Mb in size. Four potential candidate genes have been mapped to
      this region.

PMID- 8750197
TI  - Generation of a high-resolution genetic map and a YAC contig of the Lurcher locus
      on mouse chromosome 6.
AB  - Lurcher (Lc) is a semidominant mouse mutant that displays progressive
      neurodegeneration during perinatal development. This genetic lesion results in
      apoptotic neuronal death in a dosage dependent and cell autonomous manner in
      specific neurons during their terminal differentiation. To understand the
      molecular basis of the Lc mutation, we have adopted a positional cloning approach
      based on its location on mouse chromosome 6. To define the Lc locus, we have
      extended our previous analysis of an intersubspecific backcross between Mus m.
      castaneus and B6CBACa-Aw-j/A-Lc consisting of 504 animals (Norman et al. 1991).
      In addition, 580 animals of a generic backcross between Mus spretus and C57BL/6
      (The European Collaborative Interspecific Backcross) were utilized for the fine
      genetic mapping of the Lc locus. Using three RFLP markers and nine microsatellite
      markers in the vicinity of the Lc locus, we determined the order and relative
      genetic distances of these markers at a resolution of 0.1 cM. The Lc mutation was
      mapped between two flanking markers, D6Mit121 and D6Mit175, separated by a
      genetic distance of 0.5 cM. We then initiated the cloning of the genomic region
      surrounding these two markers by screening a YAC library and characterizing YAC
      end sequences for further screening. This effort has resulted in the construction
      of a YAC contig consisting of 14 YACs and spanning a 3-Mb region. Markers
      isolated from these YACs were used to further define the Lc locus, resulting in a
      physical map that places the Lc gene within an estimated 300-kb interval. This
      set of YACs and markers will serve as DNA sources for the identification of the
      Lc gene.

PMID- 8750198
TI  - An infrared fluorescent dATP for labeling DNA.
AB  - Near-infrared fluorescence provides a nonradioactive method of detection with
      high sensitivity and low background. An infrared fluorophore has been attached
      covalently to the nucleotide deoxyadenosine triphosphate (dATP) to provide a
      reagent for enzymatic labeling of various types of DNA molecules and for
      facilitating their detection with an automated DNA sequencing and analysis
      system. DNA sequencing reaction products can be labeled internally by performing
      limited polymerization utilizing infrared-labeled dATP (IR-dATP) as the sole
      source of adenine deoxynucleotide prior to a dideoxy-specific termination
      reaction. PCR products can be labeled fluorescently by the addition of limited
      quantities of IR-dATP to the amplification reaction. This latter strategy has
      been utilized for detection of short tandem repeat polymorphisms (STRPs) which
      are useful for gene mapping, genetic diagnostics, forensic analysis, and
      paternity testing. Restriction fragments can be labeled also by fill-in reactions
      of appropriate 5' overhangs. Diminutive amounts of such fluorescently labeled DNA
      molecules can be visualized rapidly and conveniently using infrared detection
      technology.

PMID- 8750199
TI  - RNA-primed PCR.
AB  - We show that RNA can serve as a primer in PCR. Use of rTth DNA polymerase is
      essential because it has strong reverse transcriptase activity. RNA primers can
      be obtained by in vitro transcription and are less costly than DNA primers, which
      are chemically synthesized. RNA-primed PCR also opens the possibility that a
      specific amplification reaction can be achieved in the absence of knowledge of
      the target nucleotide sequence.

PMID- 8750200
TI  - A highly efficient procedure for site-specific mutagenesis of full-length
      plasmids using Vent DNA polymerase.
AB  - Careful titration of Vent polymerase activity allows efficient amplification of
      full-length plasmids (12 kb). The high processivity and fidelity of this enzyme
      made oligonucleotide-directed site-specific mutagenesis of plasmids a straight
      forward process. Using only two primers, a mutagenic and a complementary, single
      base mutants of recombinant plasmids were obtained consistently with > 90%
      efficiency from a single round of PCR. This procedure also made site-specific
      deletion, insertion, and several bases mutagenesis facile and efficient.

PMID- 8750201
TI  - Differential subsequence conservation of interspersed repetitive Streptococcus
      pneumoniae BOX elements in diverse bacteria.
AB  - Evolutionary conservation of an interspersed repetitive DNA sequence, BOX, from
      Streptococcus pneumoniae was investigated to explore the mosaic nature of these
      elements. BOX elements consist of various combinations of three subunits, boxA,
      boxB, and boxC. Eight oligonucleotide probes were designed based on consensus DNA
      sequences of boxA, boxB, and boxC subunits. DNA hybridization studies and PCR
      using these probes/primers demonstrate that oligonucleotide sequences within the
      boxA subunit appear to be conserved among diverse bacterial species. The boxB and
      boxC subunits show only limited, if any, sequence conservation in bacteria other
      than S. pneumoniae. Intact BOX elements with boxA, boxB, and boxC subunits were
      only present in high copy number in pneumococcal strains. This pattern of
      differential conservation lends support to the modular nature of BOX repetitive
      elements in that boxA-like subsequences are effectively independent of boxB-like
      or boxC-like subunits in bacteria other than S. pneumoniae. Furthermore,
      dendrograms derived from repetitive sequence-based PCR (rep-PCR) fingerprints of
      S. pneumoniae isolates using the BOXA1R primer yielded clustering patterns that
      were similar to those obtained previously by other methods, suggesting that these
      repetitive sequence-based DNA fingerprints represent intrinsic properties of an
      S. pneumoniae strain's genome. Our results indicate widespread conservation of
      boxA-like subsequences in the bacterial kingdom, lend support to the mosaic
      nature of BOX in S. pneumoniae, and demonstrate the utility of boxA-based primers
      for rep-PCR fingerprinting of many microorganisms.

PMID- 8750202
TI  - Distribution of menaquinone-4, a therapeutic agent for osteoporosis, in bone and
      other tissues of rats.
AB  - [14C]Menaquinone-4 was administered orally once daily at a dose of 4 mg/kg for
      ten days to female rats of different ages to determine its blood and tissue
      distribution with particular attention to its distribution in bone. Animals aged
      10 and 30 months were either ovariectomized or sham-operated as a control, and
      young rats aged 7 weeks were used as untreated controls. Blood concentrations of
      radioactivity at 24h after each dose during repeated administration increased
      daily and approached a steady rate by the seventh dose. Higher concentrations of
      radioactivity in blood (plasma) were observed in older animals than in the
      younger ones, but there was little difference between ovariectomized rats (OVX
      rats) and sham-operated rats (Sham rats). In tissue samples collected at 1.5 h
      after administration, the liver, adipose tissue, spleen and adrenals showed
      higher concentrations of radioactivity than the other organs and the plasma. IN
      bone tissues, the bone marrow (BM) and cancellous tissue (CT) of the femur showed
      radioactivity concentrations which were higher than that in the plasma, and these
      increased during repeated administration. Finally, at 24 h after the last dose,
      the concentrations of radioactivity in bone tissues of older animals (BM, 5,807.2
      ng eq/g; CT, 5,264.8 ng eq/g in OVX rats aged 10 months and BM, 11,479.3 ng eq/g;
      CT, 4,023.0 ng eq/g in OVX rats aged 30 months) were several times higher than
      those in younger animals (BM, 2,771.6 ng eq/g; CT, 890.2 ng eq/g in 7-week-old
      untreated rats). The values in OVX rats were also higher than those in Sham rats.
      Furthermore, micro autoradiography studies of femur sections from OVX rats
      indicated that [14C] Menaquinone-4 localized in cancellous tissue where bone is
      known to be actively remodelled. The concentrations of radioactivity in
      cancellous tissue and bone marrow of OVX rats aged 10 and 30 months were
      comparable to the pharmacologically effective concentrations of Menaquinone-4
      (10(-6)-10(-5) M) in in vitro studies on bone formation. These findings suggest
      that orally administered Menaquinone-4 distributes specifically into the bone
      tissues of ovariectomized rats and this is consistent with its effect as a
      therapeutic agent for osteoporosis.

PMID- 8750203
TI  - Synthesis, properties and microbiological activity of hydrophobic derivatives of
      vitamin B12.
AB  - Long chain alkylcobalamins and long chain acyl-cyanocobalamins, two types of
      hydrophobic derivatives of vitamin B12, were synthesized. It was shown by TLC and
      determination of the partition coefficient between organic and aqueous phases
      that the hydrophobicity of alkylcobalamins and acyl-cyanocobalamins increased
      with the chain length of the alkyl or acyl group introduced into cobalamin. Long
      chain alkylcobalamins were easily converted to aquacobalamin by photoirradiation,
      but the first-order rate constant of photolysis decreased with the length of an
      alkyl group. Long chain acyl-cyanocobalamins were gradually hydrolyzed to
      cyanocobalamin in neutral or alkaline solution with the pseudo-first order rate
      constant increasing with the pH of the solution. Stabilization of acyl
      cyanocobalamins toward hydrolysis was achieved by introducing a methyl group into
      the alpha-position of an acyl group. All the long chain alkylcobalamins tested
      supported the growth of Escherichia coli 215, a cobalamin- or L-methionine
      auxotroph, and Lactobacillus leichmannii, although their activity as cobalamin
      was at most 28% and 15% that of cyanocobalamin for E. coli 215 and L.
      leichmannii, respectively.

PMID- 8750204
TI  - Changes in hepatic enzyme activities related to ethanol metabolism in mice
      following chronic ethanol administration.
AB  - Male mice of three strains, C57BL, DBA and C3H/He, were fed on commercial food
      with 10% (v/v) ethanol solution as drinking liquid ad libitum for eighty days,
      and the changes in the activities of enzymes in the metabolic pathway of ethanol
      in the liver were examined. C57BL and C3H/He mice showed a preference for
      drinking the 10% (v/v) ethanol solution, while DBA mice did not. The ethanol
      intake g/g of body weight of C3H/He mice showed the highest value among all three
      strains and that of C57BL mice tended to show higher value than that of DBA mice.
      The liver weights of C57BL and C3H/He mice increased significantly following
      chronic ethanol administration, but that of DBA did not. The cytosolic enzyme
      alcohol dehydrogenase (ADH) showed no changes in any of the strains following
      chronic ethanol administration. The microsomal ethanol-oxidizing system (MEOS) of
      C57BL mice exhibited approximately 2-fold higher activity compared to that of DBA
      and C3H/He mice but did not increase in any strain following chronic ethanol
      administration. However, the microsomal aniline hydroxylase activity in the liver
      increased significantly in C57BL and C3H/He mice following chronic administration
      of ethanol. The microsomal cytochrome P-450 content also tended to slightly
      increase in the same strains of mice. It seemed that cytochrome P-450IIE1 was
      induced in the liver microsomes of these strains. Total aldehyde dehydrogenase
      (ALDH) activities together with high-Km ALDH activity increased markedly in the
      microsomes of C57BL mice and tended to increase in C3H/He mice, while it did not
      change in DBA mice following chronic ethanol administration. In the mitochondria
      of C57BL, total ALDH activities increased slightly and high-Km ALDH activities
      tended to increase. These mitochondrial ALDH activities of C3H/He and DBA mice
      tended to increase following chronic ethanol administration. The cytosolic ALDH
      activity showed no changes in any strain of mice following chronic ethanol
      administration. It seemed that in the microsomes, the activities of enzymes
      related to oxidation of ethanol increased in C57BL and C3H/He mice, which tended
      to consume a large amount of ethanol, and did not in DBA mice which tended to
      consume a small amount of it. It seemed that the increases in activities of
      enzymes related to oxidation of acetaldehyde in the microsomes and in the
      mitochondria were responsible for the strain difference.

PMID- 8750205
TI  - Calcitonin reduced corticosterone-induced muscle proteolysis.
AB  - Two-experiments were conducted to clarify the effect of calcitonin (CT) on
      growth, muscle protein breakdown, plasma corticosterone (CTC) concentration and
      urinary calcium excretion in young growing rats treated with CTC. Rats received
      hormonal treatments for 6 days (Experiment 1) or 24 h (Experiment 2). Dose levels
      of CTC were 10 mg and 5 mg/100 g body weight/day in experiment 1 and 2,
      respectively, and that of CT was 100 m unit/100 g body weight/day in both
      experiments. Muscle protein degradation was evaluated by urinary N tau
      methylhistidine excretion. CT increased 24-h urinary calcium excretion but not 6
      day calcium excretion. CTC markedly inhibited growth, accelerated muscle protein
      degradation and increased calcium excretion in both experiments. However, very
      interestingly, CT minimized CTC-induced muscle proteolysis, and normalized the
      CTC-induced decrease in urinary calcium excretion. Furthermore, CT decreased the
      CTC-induced increase in the plasma CTC concentration. The present observations
      indicate that CT reduces CTC-induced muscle protein breakdown by reducing the
      plasma CTC concentration and that increased urinary calcium excretion due to CT
      treatment may also play a role in reducing CTC-induced muscle protein breakdown.

PMID- 8750206
TI  - The influence of dietary fatty acids and vitamin E on plasma prostanoids and
      liver microsomal alkane production in broiler chickens with regard to nutritional
      encephalomalacia.
AB  - Nutritional encephalomalacia (NE) in broiler chicken is considered as a
      peroxidative dysfunction caused by vitamin E-deficient diets. A feeding
      experiment was performed to investigate the consequences of feeding different
      fats in combination with increasing amounts of vitamin E on liver lipid
      peroxidation and plasma prostanoid pattern. Newly hatched chicks from hens on a
      vitamin E-poor diet were fed with either mainly linolenic, linoleic or oleic acid
      rich oils in a vitamin E-deficient (5 ppm) basic diet. The animals were
      supplemented with vitamin E on three levels (0, 20 or 120 ppm). On appearance of
      the first symptoms of NE after 8 days post-hatching, the animals were examined.
      Typical symptoms with a high incidence only occurred in the group fed linoleic
      acid and 5 ppm vitamin E. Plasma prostanoids and microsomal alkane production in
      liver as a measure of endogenous lipid peroxidation were determined. The dietary
      conditions affected plasma prostaglandin E2 and thromboxane A2, but not
      prostacyclin. However, it seems unlikely that the prostanoids are involved in the
      pathogenesis of NE. Liver lipid peroxidation increased in vitamin E deficiency.
      The level of alkanes depended on the type of fat supplied. The consequences of
      the different dietary fats in combination with vitamin E deficiency on
      peroxidative metabolism of broiler chickens are evident, indicating that a high
      level of oxidative stress is imposed by the linoleic acid-rich fat.

PMID- 8750207
TI  - Effects of spinach leaf protein concentrate on the serum cholesterol and amino
      acid concentrations in rats fed a cholesterol-free diet.
AB  - The effects of spinach leaf protein concentrate (SPPC) on serum and liver lipid
      concentrations and on serum free amino acid concentrations were examined in rats
      fed a cholesterol-free diet containing 2 and 10% fats. The serum total
      cholesterol, triacylglycerol and phospholipid concentrations in the rats fed an
      SPPC diet containing 2% corn oil were significantly lower than those of the rats
      fed a corresponding casein diet. When 10% corn oil or lard was used, the serum
      cholesterol-lowering effect of the SPPC became insignificant, but the serum and
      liver triacylglycerol concentrations were kept at significantly lower levels.
      Both the amounts of fecal neutral steroids and bile acids were significantly
      higher in the rats fed the SPPC than those of the casein-fed rats. The
      concentrations of serum threonine, serine, glutamine, glycine, cystine, and
      isoleucine were significantly higher in the rats fed the SPPC diet containing 2%
      corn oil compared with those of the control rats, but when the dietary fat was
      raised to 10%, only glycine showed a higher serum concentration. These results
      indicate that the SPPC has a stronger cholesterol-lowering effect at a lower
      dietary fat level, 2%, and the activity is partly due to the inhibition of
      intestinal absorption of cholesterol and bile acid, and partly due to an increase
      in the concentration of some of the serum amino acids.

PMID- 8750208
TI  - Yolk sac concentration of prostaglandin E2 in diabetic pregnancy: further clues
      to the etiology of diabetic embryopathy.
AB  - Fetal malformation associated with maternal diabetes occurs before the seventh
      week of pregnancy. Current hypotheses suggest that the diabetic milieu causes a
      reduction in phosphatidylinositol turnover, leading to a disruption in the
      arachidonic acid cascade and resulting in a deficiency of prostaglandins,
      particularly prostaglandin E2. This in turn results in a wide variety of
      congenital anomalies. This hypothesis has not been tested experimentally in
      humans. The yolk sac is thought to be the most important source of nutrition in
      early pregnancy. We sought to compare yolk sac prostaglandin levels in normal and
      diabetic women. Under ultrasonographic guidance, yolk sacs were aspirated form 8
      normal and 12 diabetic women ranging from 8 to 10 weeks gestational age prior to
      elective abortion. Prostaglandin E2 levels were determined using RIA. The mean
      prostaglandin E2 level in normal controls was 3605 pg/mL, and was undetected in
      all of the yolk sacs aspirated from diabetic women (P < 0.001). Yolk sac diameter
      in diabetic pregnancies was 1.2 mm larger than that of normal pregnancies. The
      functional and morphological changes demonstrated in this study may increase our
      understanding of the pathophysiology of diabetic embryopathy.

PMID- 8750209
TI  - Lipoxygenase products and expression of 5-lipoxygenase and 5-lipoxygenase
      activating protein in human cultured synovial cells.
AB  - 5-Lipoxygenase products are pro-inflammatory mediators. Their roles and cellular
      origin in chronic inflammatory rheumatisms such as rheumatoid arthritis (RA) are
      poorly understood. The expression of arachidonate 5-lipoxygenase (5-LOX,
      arachidonate: oxygen 5-oxydoreductase; EC 1.13.11.34) and the 5-lipoxygenase
      activating protein (FLAP) genes in osteoarthritis and RA synoviocytes was studied
      at the transcriptional level by reverse transcription-polymerase chain reaction
      (RT-PCR) methodology. Arachidonic acid metabolism was analyzed by reverse-phase
      high pressure liquid chromatography. 5-LOX and FLAP mRNA were detectable using RT
      PCR in all sources of synoviocytes tested. The expression of 5-LOX and FLAP mRNA
      led to the synthesis of 5-LOX metabolites. 12- and 15-LOX activities were also
      present. These LOX products can participate in inflammatory processes leading to
      joint destruction in RA.

PMID- 8750210
TI  - Prostaglandin F2 alpha, progesterone and oxytocin production by cultured bovine
      luteal cells treated with prostaglandin E2 and pregnancy-specific protein B.
AB  - The objectives of this experiment were to study the effects of pregnancy-specific
      protein B (PSPB) and prostaglandin E2 (PGE2) on bovine luteal cell progesterone
      (P4), prostaglandin F2 alpha (PGF2 alpha) and oxytocin production. Corpora lutea
      were collected during the mid- (days 10-12; n = 5) or late-luteal (days 17-18; n
      = 5) stages of the estrous cycle. Luteal cells were dispersed and accessory cells
      removed. Luteal cells (1.5 x 10(5)) were incubated in a 3 x 3 factorial
      arrangement and treated with PSPB (0, 2.5, or 5.0 micrograms) and PGE2 (0, 100,
      or 200 ng) in 500 microL of Ham's F-12 medium. All cells were incubated for 18 h
      before adding treatments. Samples were then collected at 6 h and 12 h. During the
      18 h pretreatment period, P4, PGF2 alpha, and oxytocin production was similar
      between the prospective treatment groups. The PSPB failed to increase P4
      production. The PGE2 x time interaction showed that P4 increased in response to
      PGE2 treatment at 6 h (P < 0.001) and 12 h (P < 0.03). Also, the stage x time
      interaction indicated that mid-stage cells produced more (P < .001) P4 than late
      stage cells during the pretreatment period at 6 h and 12 h. The PSPB did not
      alter PGF2 alpha production by mid-stage cells, but increased (P < .05) PGF2
      alpha by late-stage cells. Also, PGE2 stimulated (P < 0.001) PGF2 alpha secretion
      by both mid- and late-stage cells; luteal cells treated with 200 ng of PGE2
      produced more (P < 0.001) PGF2 alpha than 100 ng of PGE2. Oxytocin secretion was
      not changed by treatment with PGE2 or PSPB. Oxytocin production was greater (P <
      0.001) by mid-stage than late-stage cells during the pretreatment period at 6 h
      and 12 h. Oxytocin production was similar between the 6 h and 12 h culture times
      within stage of the cycle. These data indicate that PSPB does not change bovine
      luteal cell P4 or oxytocin production, but elevates PGF2 alpha in late-stage
      cells. The PGE2 increases both P4 and PGF2 alpha, but does not alter oxytocin
      production. Lastly, PSPB and PGE2 do not interact to promote P4 PGF2 alpha, or
      oxytocin production by cultured bovine luteal cells.

PMID- 8750211
TI  - Expression of insulin-like growth factor I mRNA in rat luteal tissue increases
      with functional regression of the corpus luteum.
AB  - The expression of insulin-like growth factor (IGF-I) messenger ribonucleic acid
      (mRNA) in rat corpora lutea (CL) was determined during the second half of
      pregnancy and early lactation, and the effect of prostaglandin F2 alpha on
      expression was examined during late pregnancy. Northern blot analysis revealed 4
      species of transcripts in CL. Radioactivity of dot blots was measured directly
      for quantitative analysis of expression. The expression in CL increased during
      the second half of pregnancy, peaked around parturition, and declined thereafter.
      The injection of 1 mg of prostaglandin F2 alpha at 1300 and 1800 h on day 18 of
      pregnancy, which decreased plasma progesterone concentration, doubled luteal
      expression of IGF-I mRNA 1 day later. These results suggest that functional
      regression of the corpus luteum is correlated with the increased expression of
      IGF-I mRNA in luteal tissue in rats.

PMID- 8750212
TI  - Effects of prostaglandin antagonist phloretin derivatives on mouse ear edema
      induced with different skin irritants.
AB  - Edema was induced in one ear of male mice of the CFLP strain with solutions of
      different skin irritants (croton oil 10 microL/35 micrograms, dithranol 10
      microL/30 micrograms, capsaicin 10 microL/40 micrograms or arachidonic acid to 10
      microL/2 mg per ear). Edema, determined by the edema-disk gravimetric technique,
      was inhibited in a dose-dependent manner by the intraperitoneally administered
      prostaglandin antagonists polyphloretin phosphate (PPP) or di-4-phloretin
      phosphate (DPP). With croton oil-induced mouse ear edema, DPP 10 mg/kg caused a
      38% inhibition, PPP 25 mg/kg a 33% inhibition. With dithranol-induced edema DPP
      0.5 mg/kg caused a 57% inhibition, while PPP 25 mg/kg was needed to exert a
      similar effect. Doses of DPP and PPP needed to cause a > 40% inhibition of edema
      were 10 mg/kg and 25 mg/kg, respectively, for capsaicin, and 25 mg/kg and 100
      mg/kg for arachidonic acid. The inhibition of the ear edema by the phloretin
      derivatives was: dithranol > croton oil > capsaicin > arachidonic acid. This
      probably reflects the different contributions of prostaglandins to the
      inflammation.

PMID- 8750213
TI  - Antithrombotic effects of peroxynitrite: inhibition and reversal of aggregation
      in human platelets.
AB  - The inhibition of platelet aggregation by peroxynitrite, a reactive oxygen
      species derived from the interaction of nitric oxide (NO) and superoxide, was
      examined in platelet-rich plasma. In this report, we have used a preparation of
      peroxynitrite that was free of H2O2 and MnO2. As such, peroxynitrite dose
      dependently (50-200 microM) inhibited aggregation of human platelets stimulated
      by ADP (5 microM), collagen (0.5 microgram), thrombin (0.5U/microL) and U46619 (1
      microM). In addition, peroxynitrite reversed platelet aggregation induced by
      collagen, ADP, and thrombin. Peroxynitrite, preincubated with platelet-poor
      plasma or albumin (7%) for 30 min, did not alter the inhibition of platelet
      aggregation. This suggested that the inhibitory action of peroxynitrite may be
      due to nitrosylation of proteins, which by themselves possess activity, rather
      than conversion to NO or NO donors. Furthermore, we show that peroxynitrite
      increased the cGMP level only at 200 microM concentrations, further suggesting
      that the action of peroxynitrite was not completely due to its conversion to NO
      or NO donors.

PMID- 8750214
TI  - Diabetes in the Eastern Mediterranean (Middle East) region: the World Health
      Organization responds to a major public health challenge.

PMID- 8750215
TI  - Nephropathy in type 1 diabetes: the role of genetic factors.
AB  - Diabetic nephropathy affects up to 30% of all patients with Type 1 (insulin
      dependent) diabetes and is associated with a high morbidity and mortality. A
      number of studies have suggested that, unlike retinopathy or neuropathy, the
      influence of hereditary factors on the development of nephropathy is strong. Much
      interest has focused on possible genetic markers indicating an increased risk for
      developing diabetic nephropathy. It is envisaged that patients with Type 1
      diabetes may be screened at diagnosis for increased susceptibility to nephropathy
      and subsequently have intensified follow up and possibly even prophylactic
      therapy in order to prevent progression to nephropathy. Two groups of candidate
      genes have so far been of particular interest: those implicated in the aetiology
      of hypertension, and those involved in the metabolism of glomerular basement
      membrane proteins. This article aims to review the evidence suggesting a role for
      hereditary factors, possible genetic models, and the genetic loci thought to be
      involved.

PMID- 8750216
TI  - The cost of insulin-dependent diabetes mellitus (IDDM) in England and Wales.
AB  - This study estimates the direct health and social care costs of insulin-dependent
      diabetes mellitus (IDDM) in England and Wales in 1992 to be 96 million pounds, or
      1021 pounds per person in a population with IDDM estimated at 94,000 individuals.
      These costs include insulin maintenance, hospitalization, GP and out-patient
      consultations, renal replacement therapy, and payments to informal carers.
      Expenditure is concentrated on younger age groups, with one-third of the total
      expended on those aged 0-24. Around one-half of the total costs can be directly
      attributed to IDDM, with the remainder associated with a range of complications
      of the disease. The single largest area of service expenditure is renal
      replacement therapy. The cost estimates are most sensitive to incidence rates of
      IDDM, numbers on dialysis and average duration of dialysis. A further 113 million
      pounds may be lost each year due to premature deaths resulting in lost productive
      contributions to the economy. The direct and indirect costs of IDDM are therefore
      significant. The cost of illness framework presented here should facilitate the
      economic evaluation of new and existing treatment regimens, which may improve
      value for money by reducing costs and/or increasing the quality or quantity of
      life for people with IDDM.

PMID- 8750217
TI  - Counting the cost of diabetic hospital admissions from a multi-ethnic population
      in Trinidad.
AB  - Many middle-income countries are experiencing an increase in diabetes mellitus
      but patterns of morbidity and resource use from diabetes in developing countries
      have not been well described. We evaluated hospital admission with diabetes among
      different ethnic groups in Trinidad. We compiled a register of all patients with
      diabetes admitted to adult medical, general surgical, and ophthalmology wards at
      Port of Spain Hospital, Trinidad. During 26 weeks, 1447 patients with diabetes
      had 1722 admissions. Annual admission rates, standardized to the World
      Population, for the catchment population aged 30-64 years were 1031 (95% CI 928
      to 1134) per 100,000 in men and 1354 (1240 to 1468) per 100,000 in women.
      Compared with the total population, admission rates were 33% higher in the Indian
      origin population and 47% lower in those of mixed ethnicity. The age-standardized
      rate of amputation with diabetes in the general population aged 30-64 years was
      54 (37 to 71) per 100,000. The hospital admission fatality rate was 8.9% (95%CI
      7.6% to 10.2%). Mortality was associated with increasing age, admission with
      hyperglycaemia, elevated serum creatinine, cardiac failure or stroke and with
      lower-limb amputation during admission. Diabetes accounted for 13.6% of hospital
      admissions and 23% of hospital bed occupancy. Admissions associated with
      disorders of blood glucose control or foot problems accounted for 52% of diabetic
      hospital bed occupancy. The annual cost of admissions with diabetes was
      conservatively estimated at TT+ 10.66 million (UK 1.24 million pounds). In this
      community diabetes admission rates were high and varied according to the
      prevalence of diabetes. Admissions, fatalities and resource use were associated
      with acute and chronic complications of diabetes. Investing in better quality
      preventive clinical care for diabetes might provide an economically advantageous
      policy for countries like Trinidad and Tobago.

PMID- 8750218
TI  - Microvascular function in type 2 (non-insulin-dependent) diabetes: improved
      vasodilation after one year of good glycaemic control.
AB  - Abnormalities of microvascular function may be important in the development of
      diabetic microangiopathy. The major functional abnormality identified in patients
      with Type 2 diabetes has been a marked limitation of microvascular vasodilation,
      which is present from the time of diagnosis. The effects of sustained
      improvements in glycaemic control on vasodilator capacity in Type 2 diabetes are
      unknown. Twelve Type 2 diabetic patients were studied prospectively for 1 year
      after diagnosis. The reduced maximum hyperaemic response to local heating of the
      foot skin present at the time of diagnosis remained unchanged after 3 months of
      improved glycaemic control (1.12 +/- 0.56 V at diagnosis vs 1.21 +/- 0.69 V at 3
      months, mean +/- SD; p = 0.25), but was improved after 1 year (1.42 +/- 0.91 V; p
      = 0.04 vs 3 months). The percentage increase in maximum hyperaemia correlated
      with the percentage decrease in HbA1c (rs = 0.53, p = 0.04). These results
      suggest that the early microvascular abnormalities demonstrated in Type 2
      diabetes are potentially reversible and provide a further reason for striving for
      optimal glycaemic control in this patient group.

PMID- 8750219
TI  - The urinary concentration of sialic acid is increased in non-insulin-dependent
      diabetic patients with microangiopathy: a possible useful marker for diabetic
      microangiopathy.
AB  - In order to investigate the relationship between urinary excretion of sialic acid
      and the severity of diabetic microangiopathy, urinary levels of sialic acid were
      determined in patients with non-insulin-dependent diabetes mellitus. The urinary
      molar ratio of sialic acid to creatinine in the diabetic patients was
      significantly higher than in the healthy controls (p < 0.01). Moreover, the
      urinary ratio was found to be gradually increased with the degree of diabetic
      microangiopathy. Urine molar ratio of sialic acid to creatinine in patients with
      proliferative diabetic retinopathy was significantly higher than in patients
      without retinopathy (p < 0.01). Urinary excretion in patients with
      macroproteinuria was also significantly higher than in patients without
      nephropathy (p < 0.01). Since urinary levels of sialic acid are proportionally
      increased with the severity of diabetic microangiopathy, the measurement of
      urinary sialic acid could become a useful biochemical means to monitor the degree
      of diabetic microangiopathy.

PMID- 8750220
TI  - Effect of treatment with an aldose-reductase inhibitor on symptomatic carpal
      tunnel syndrome in type 2 diabetes.
AB  - The aim of this study was to test the efficacy of the aldose-reductase inhibitor
      Tolrestat in the treatment of carpal tunnel syndrome in Type 2 diabetic patients.
      Seventeen patients were treated with Tolrestat (200 mg daily for 12 months)
      clinical and neurophysiological evaluations were performed at baseline, 6 and 12
      months; symptoms and blood glucose control were assessed at baseline, 2, 6, and
      12 months. Thirteen Type 2 diabetic patients suffering from symptomatic carpal
      tunnel syndrome served as controls. Neurophysiological studies showed improvement
      in the sensory conduction velocity of the median nerve between forefinger and
      wrist (baseline 37.5 +/- 4.3 vs 6 months 41.3 +/- 5.7 ms-1, p < 0.0005 and
      baseline vs 12 months 41.4 +/- 8.2 ms-1, p < 0.005) but not between wrist and
      elbow. The terminal latency index of the median nerve was unchanged.
      Paraesthesiae and pain improved in terms of intensity and frequency. Blood
      glucose control was not significantly changed. We conclude that treatment of this
      case series with Tolrestat appears to produce beneficial effect on the outcome of
      carpal tunnel syndrome in diabetic patients.

PMID- 8750221
TI  - Symptoms, hormones, and glucose fluxes during a gradual hypoglycaemia induced by
      intraperitoneal vs venous insulin infusion in Type I diabetes.
AB  - Intraperitoneal (IP) insulin infusion with programmable implantable pumps is
      associated with a reduction in hypoglycaemic events when compared to intensive
      diabetes management with subcutaneous insulin in patients with Type 1 diabetes
      mellitus. The mechanism may involve more physiological insulin kinetics, lower
      peripheral insulin levels or a specific hepatic action of portal insulin on
      hypoglycaemic counter regulation. To investigate the latter two hypotheses, we
      performed two hypoglycaemic clamps (controlled blood glucose decrement to 2.2
      mmol l-1) in random order in 12 Type 1 diabetic patients. Insulin was infused
      either IP or IV for 150 min, at rates chosen to generate similar peripheral
      insulin levels (1 mU/kg-1 min-1 IV or 2 mU/kg-1 min-1 IP, n = 6) to evaluate
      direct hepatic action, or at similar rates (1 mU/kg-1 min-1 IV and IP, n = 6) to
      evaluate IP indirect effects via lower peripheral insulinaemia. Hepatic glucose
      production and glucose utilization were measured by [6.6 2H] glucose dilution
      technique. Glucose production was lower (1.7 +/- 0.4 vs 0.5 +/- 0.4 mg kg-1 min
      1, p < 0.05), and utilization was similar at the end of the matched-insulinaemia
      IV and IP clamps, respectively. By contrast, glucose production was higher (1.7
      +/- 0.5 IV vs 2.7 +/- 0.3 IP mg kg-1 min-1, p < 0.01) and glucose utilization
      lower (4.4 +/- 1.0 IV vs 3.3 +/- 0.2 IP mg kg-1 min-1, p < 0.05) with IP delivery
      at the end of the matched-dose clamps. Counterregulatory hormones and
      hypoglycaemic symptoms increased similarly in all clamps. In summary, IP insulin,
      when compared to IV insulin at similar delivery rates, but not at similar
      insulinaemia, is associated with a less negative glucose balance (glucose
      production-glucose utilization) during hypoglycaemia. Such a mechanism may play a
      role in the reduced hypoglycaemic risk seen with IP implantable pumps.

PMID- 8750222
TI  - The effect of acute (60 minute) insulin stimulation upon human skeletal muscle
      glycogen synthase and protein phosphatase-1 in non-insulin-dependent diabetic
      patients and control subjects.
AB  - Previous studies have established that activation of muscle glycogen synthase
      (GS) is abnormal in non-insulin-dependent diabetes mellitus (NIDDM). Insulin
      mediated activation of GS depends upon protein phosphatase-1 (PP1), which
      dephosphorylates the relevant sites of GS. In order to determine whether defects
      in PP1 activation cause subnormal activation of GS or whether PP1 activation
      itself is normal, we administered a short insulin infusion to 8 NIDDM subjects
      and 8 healthy controls matched for gender, age, and body mass index (BMI). GS
      fractional activity and PP1 activity were determined in biopsies taken from the
      gastrocnemius muscle before and after 60 min insulin infusion (0.1 U kg h-1). In
      the NIDDM group, muscle GS fractional activity was 6.8 +/- 1.6 and 10.0 +/- 1.5%
      (mean +/- SEM) (p = 0.11) before and after insulin infusion. In the control
      group, muscle GS fractional activity increased from 7.3 +/- 2.0 to 13.3 +/- 2.7%
      (p < 0.02). PP1 activity had returned towards basal levels after insulin
      infusion; NIDDM group 156 +/- 24.7 to 184.1 +/- 28.1 U mg-1; control group 220.8
      +/- 30.1 to 233.8 +/- 29.8 U mg-1. In the NIDDM group there was a positive
      correlation between the increases in GS fractional activity and PP1 activity
      following insulin stimulation r = 0.77; p < 0.025). These data indicate that in
      vivo insulin-dependent activation of muscle PP1 is transient in normal subjects
      but is delayed in NIDDM. The defect in GS activation in NIDDM is likely to be
      proximal to PP1 in the pathway of transmission of the insulin signal.

PMID- 8750223
TI  - Pakistan national diabetes survey: prevalence of glucose intolerance and
      associated factors in Shikarpur, Sindh Province.
AB  - The prevalence of diabetes mellitus and impaired glucose tolerance (IGT) and
      their relationship to age and obesity was estimated in the rural town of
      Shikarpur in Sindh Province, Pakistan by a population-based survey in 1994. Oral
      glucose tolerance tests were performed in a stratified random sample of 967
      adults (387 men, 580 women) aged 25 years and above. The diagnoses of diabetes
      and IGT were made on the basis of WHO criteria. The response rate was 71% for men
      and 80% for women. The prevalence of diabetes was 16.2% (9.0% known, 7.2% newly
      diagnosed) in men, and 11.7% (6.3% known, 5.3% newly diagnosed) in women. The
      prevalence rose with age to a peak of 30% and 21% in 65-74 year-old men and women
      respectively. IGT was detected in 8.2% of men and 14.3% of women. Thus, total
      glucose intolerance (diabetes and IGT combined) was present in 25% of subjects
      examined. These results indicate that glucose intolerance in South Asians can no
      longer be regarded as a problem confined to migrant communities. Of the 72
      subjects previously known to have diabetes, none was using insulin treatment, but
      57 (79%) took oral hypoglycaemic agents. Central obesity and positive family
      history were strongly associated with diabetes, as was prevalence of
      hypertension. The association with central obesity was greater for women than for
      men, and suggests important, modifiable risk factor(s) related to lifestyle.

PMID- 8750224
TI  - High prevalence of diabetes mellitus and impaired glucose tolerance in the
      Sultanate of Oman: results of the 1991 national survey.
AB  - A national survey of glucose intolerance and cardiovascular disease risk factors
      in Oman has demonstrated a high prevalence of diabetes (10%) and impaired glucose
      tolerance (IGT, 13% in females and 8% in males). Prevalence of diabetes rose with
      age to a maximum of over 30% in both sexes. Prevalence of total glucose
      intolerance (diabetes and IGT combined) exceeded 50% in the seventh (females) and
      eighth (males) decade of life.

PMID- 8750225
TI  - Diabetes mellitus in Egypt: risk factors and prevalence.
AB  - Major sociodemographic changes have occurred in Egypt to promote the development
      of noncommunicable diseases. We have performed a cross-sectional, population
      based survey of persons > or = 20 years of age in Cairo and surrounding rural
      villages to describe the prevalence of diabetes risk factors, diagnosed diabetes,
      previously undiagnosed diabetes, and impaired glucose tolerance by age, sex,
      rural and urban residence, and socioeconomic status (SES). In the survey, we
      identified 6052 eligible households: 76% of household respondents completed a
      household examination and 72% of selected household respondents subsequently
      completed a medical examination. Exercise was assessed by questionnaire;
      adiposity by measurement of height, weight, and girths; and diabetes by history
      and 2-h 75 g oral glucose tolerance test. In rural areas, 52% of persons > or =
      20 years of age were sedentary, 16% were obese, and 4.9% had diabetes. In lower
      SES urban areas, 73% were sedentary, 37% were obese, and 13.5% had diabetes. In
      higher SES urban areas, 89% were sedentary, 49% were obese, and 20% had diabetes.
      The combined prevalence of diagnosed and undiagnosed diabetes in the Egyptian
      population > or = 20 years of age was estimated to be 9.3%. Approximately half
      the diabetes was diagnosed and the other half was previously undiagnosed. The
      prevalence of diabetes in Egypt is high, and the gradient in risk factors and
      disease from rural to urban areas and in urban areas from lower to higher SES
      suggest that diabetes is a major, emerging clinical and public health problem in
      Egypt.

PMID- 8750226
TI  - The insulin-dependent diabetic patient: perceptions and preferences.

PMID- 8750227
TI  - Frequency, severity and symptomatology of hypoglycaemia induced by human and
      porcine insulin -letter-.

PMID- 8750228
TI  - Effects of adenosine diphosphate on the structure of myosin cross-bridges: an X
      ray diffraction study on a single skinned frog muscle fibre.
AB  - Using a technique to obtain a detailed X-ray diffraction pattern from a single
      skinned frog muscle fibre, we studied the effects of ADP on the structure and
      arrangement of myosin heads. An imaging plate and a cooled-CCD X-ray detector
      were used to record the diffraction patterns. Addition of 1 mM ADP to a rigor
      fibre increased the intensity of the third-order meridional reflection of the
      myosin repeat by 50-85%. The intensity of the sixth-order meridional reflection
      also increased. After removing the ADP, these intensities decreased but did not
      return to the level before the ADP was added. No significant changes were
      observed in the intensities of the equatorial reflections and the actin layer
      lines. These results suggest that, upon ADP binding, the conformation of a myosin
      head changes without detaching from actin. The structural change may involve a
      relative motion between domains of the myosin head by the closure of the cleft to
      which an ADP molecule binds.

PMID- 8750229
TI  - Isolation and characterization of a kettin-like protein from crayfish claw
      muscle.
AB  - A 540 kDa protein was isolated from crayfish claw muscle (closer). The secondary
      structure mainly consisted of beta-sheet (70%). The rotary shadowed images were
      long filaments, 300-360 nm long. It is localized in the sides of the Z-lines
      extending to the I band and elongatable upon stretch of muscle. Immunological
      crossreactivities strongly suggested that this protein corresponds to kettin (500
      700 kDa) of insect striated muscle. In view of molecular shape and secondary
      structure, and immunological crossreactivities, it is suggested that this kettin
      like protein belongs to connectin/titin family of striated muscle.

PMID- 8750230
TI  - Intermediate filament proteins increase during chronic stimulation of skeletal
      muscle.
AB  - Chronic low-frequency electrical stimulation of rabbit fast-twitch skeletal
      muscle induces increased levels of two intermediate filament proteins, desmin and
      vimentin, during the first 3 weeks of stimulation. These increases occur over the
      same timecourse as reported shifts in alpha-actinin expression and increased Z
      disc width, but precede the fast-to-slow shifts in contractile proteins, which
      have been described by others. Desmin and vimentin levels increase during the
      first 2 weeks of stimulation, at which time the increase in desmin appears to
      plateau while vimentin continues to increase significantly through 3 weeks of
      stimulation. Absolute amounts of vimentin are lower than desmin at all time
      points, however increases in desmin and vimentin levels are strongly correlated
      during the stimulation period, suggesting that the two proteins are coordinately
      increased during the initial phases of muscle transformation. We suggest that
      rapid increases in the expression of intermediate filament proteins, which
      coincide with alterations in Z-disc structure, may indicate a fortification of
      the force-bearing ultrastructure of the muscle fibre in response to the increased
      activity that is induced by stimulation. The presence of vimentin and elevated
      levels of desmin expression suggest that mature skeletal muscle reverts toward a
      developmental program of intermediate filament protein expression during fast-to
      slow transformation.

PMID- 8750231
TI  - Porin-type 1 proteins in sarcoplasmic reticulum and plasmalemma of striated
      muscle fibres.
AB  - The location of porin-type 1 proteins in mammalian striated muscle has been
      assessed using immunogold electron microscopy with an anti-porin 31HL monoclonal
      antibody as the primary antibody. Gold particles were found on the mitochondrial
      outer membrane, the sarcoplasmic reticulum and plasmalemma in longitudinal
      sections of rat and rabbit skeletal muscle and rabbit and sheep cardiac muscle.
      The relative densities of gold particles in the mitochondrial outer membrane,
      sarcoplasmic reticulum and plasmalemma were 7:3:1 in white sternomastoid muscle,
      for example. Skeletal and cardiac sarcoplasmic reticulum vesicles, which had been
      fractionated by discontinuous sucrose density centrifugation, were subjected to
      SDS-polyacrylamide gel electrophoresis and Western blotting. The anti-porin 31HL
      monoclonal antibody detected a band of relative molecular mass (M(r)) 31,000 in
      all muscle sarcoplasmic reticulum vesicle fractions and also in liver
      mitochondria. The intensity of immunostaining of the sarcoplasmic reticulum
      fractions was 2.5-10% that of mitochondrial outer membranes per microgram of
      membrane protein blotted. Contamination of the sarcoplasmic reticulum fractions
      by mitochondrial outer membrane was < 0.75% as determined from the specific
      activity of monoamine oxidase. Thus, only a small part of the porin detected in
      sarcoplasmic reticulum vesicles can be attributed to mitochondrial contamination.
      These results show that porin-type1 immunoreactivity is not restricted to
      mitochondria but found in the sarcoplasmic reticulum and plasmalemma of both
      mammalian skeletal and cardiac muscle.

PMID- 8750232
TI  - Effects of alpha-cyano-4-hydroxycinnamic acid on fatigue and recovery of isolated
      mouse muscle.
AB  - Fatigue and recovery of mouse soleus and extensor digitorum longus muscles were
      investigated in standard saline and in saline containing the lactate + hydrogen
      ion transport blocker, alpha-cyano-4-hydroxycinnamic acid (cinnamate). The
      fatigue protocol was a series of brief isometric tetani which reduced isometric
      force by about 25%. Recovery was monitored by test tetani during recovery. Both
      muscles recovered completely in standard saline. Soleus muscle also recovered
      completely in the presence of cinnamate, whereas extensor digitorum longus hardly
      recovered at all. Force during fatigue and recovery can be described in a
      mathematical simulation in which force depends on intracellular inorganic
      phosphate and pH, and the only effect of cinnamate is to block lactate + hydrogen
      ion transport. The results of the simulation suggest that during the fatiguing
      series of tetani pH changes are small and have a negligible effect on force, but
      pH is a major determinant of the timecourse of recovery in extensor digitorum
      longus.

PMID- 8750233
TI  - Expression of myosin heavy chain and of myogenic regulatory factor genes in fast
      or slow rabbit muscle satellite cell cultures.
AB  - We investigated the myogenic properties of rabbit fast or slow muscle satellite
      cells during their differentiation in culture, with a particular attention to the
      expression of myosin heavy chain and myogenic regulatory factor genes. Satellite
      cells were isolated from Semimembranosus proprius (slow-twitch muscle; 100% type
      I fibres) and Semimembranosus accessorius (fast-twitch muscle; almost 100% type
      II fibres) muscles of 3-month-old rabbits. Satellite cells in culture possess
      different behaviours according to their origin. Cells isolated from slow muscle
      proliferate faster, fuse earlier into more numerous myotubes and mature more
      rapidly into striated contractile fibres than do cells isolated from fast muscle.
      This pattern of proliferation and differentiation is also seen in the expression
      of myogenic regulatory factor genes. Myf5 is detected in both fast or slow 6-day
      old cell cultures, when satellite cells are in the exponential stage of
      proliferation. MyoD and myogenin are subsequently detected in slow satellite cell
      cultures, but their expression in fast cell cultures is delayed by 2 and 4 days
      respectively. MRF4 is detected in both types of cultures when they contain
      striated and contractile myofibres. Muscle-specific myosin heavy chains are
      expressed earlier in slow satellite cell cultures. No adult myosin heavy chain
      isoforms are detected in fast cell cultures for 13 days, whereas cultures from
      slow cells express neonatal, adult slow and adult fast myosin heavy chain
      isoforms at that time. In both fast and slow satellite cell cultures containing
      striated contractile fibres, neonatal and adult myosin heavy chain isoforms are
      coexpressed. However, cultures made from satellite cells derived from slow
      muscles express the slow myosin heavy chain isoform, in addition to the neonatal
      and the fast isoforms. These results are further supported by the expression of
      the mRNA encoding the adult myosin heavy chain isoforms. These data provide
      further evidence for the existence of satellite cell diversity between two rabbit
      muscles of different fibre-type composition, and also suggest the existence of
      differently preprogrammed satellite cells.

PMID- 8750234
TI  - Comparison of the foetal development of muscle in normal and double-muscled
      cattle.
AB  - Muscle differentiation was studied in foetal Semitendinosus muscle from normal
      cattle and those with the 'culard' gene of muscular hypertrophy sampled at 90,
      130, 170 and 210 days of foetal life. The different fibre types were
      characterized by immunohistochemistry with antibodies specific to different
      isoforms of myosin heavy chains. The isoforms were separated by electrophoresis,
      identified by immunoblotting and quantified by ELISA. In double-muscled animals,
      there was a slower rate of differentiation in the first generation of cells, most
      markedly apparent at 90 days. At 130 days, differentiation was retarded mainly in
      the second generation, while at 170 days there was no longer any difference
      between the two animal types in the differentiation of first generation cells,
      which were totally slow in both. At the same stage however, type IIC fibres in
      double-muscled animals were much slower in appearing and continued to be so at
      210 days, albeit to a lesser extent. These findings show that differentiation of
      the muscle fibres occurs at a slower rate in double-muscled foetuses particularly
      during the first two-thirds of foetal life.

PMID- 8750235
TI  - Review: compilation and characteristics of dedicated transcription factors in
      Saccharomyces cerevisiae.

PMID- 8750236
TI  - The mae1 gene of Schizosaccharomyces pombe encodes a permease for malate and
      other C4 dicarboxylic acids.
AB  - The mae1 gene of the yeast Schizosaccharomyces pombe was identified on the basis
      of its ability to complement a mutant defective in the transport of malic acid.
      Analysis of the DNA sequence revealed an open reading frame of 1314 base pairs,
      encoding a polypeptide of 438 amino acids with a predicted molecular weight of 49
      kDa. A hydropathy profile of the predicted amino acid sequence revealed a protein
      with ten membrane-spanning or associated domains and hydrophilic N- and C-
      termini. The predicted secondary structure of the protein in similar to models
      proposed for other integral membrane proteins from both prokaryotes and
      eukaryotes. The S. pombe mae1 gene encodes a single mRNA of 1.5 kb. The mea1 gene
      is expressed constitutively and is not subject to catabolite repression as was
      previously reported for the malate permease systems of Candida utilis and
      Hansenula anomala. The mae1 gene was mapped 2842 bp 5' to the MFml gene on
      chromosome I. Transport assays revealed that the mae1 gene encodes a permease
      involved in the uptake of L-malate, succinate and malonic acid.

PMID- 8750237
TI  - Detection method for polygalacturonase-producing strains of Saccharomyces
      cerevisiae.
AB  - In the presence of glycerol or ethanol, SCPP (a strain of Saccharomyces
      cerevisiae that expresses pectinolytic activity) is capable of utilizing
      galacturonic acid or pectins for growth purposes. We now establish a relationship
      between the pectinolytic power of various strains of S. cerevisiae and their
      ability to grow on a pectin/glycerol-based medium. This property is further
      exploited for the detection of polygalacturonase-producing strains of S.
      cerevisiae.

PMID- 8750238
TI  - Analysis of copper-induced metallothionein expression using autonomously
      replicating plasmids in Candida glabrata.
AB  - Candida glabrata strains and a stable plasmid were developed that were suitable
      for analysis of copper-inducible expression from promoters of the three
      metallothionein (MT) genes. The two homologous MTII genes, MTIIa and MTIIb,
      encode the same polypeptide but are differentially induced by copper salts. MTIIb
      is more highly inducible than MTIIa and cells harboring a single MTIIb exhibit a
      greater resistance to copper salts compared to cells harboring a single MTIIa.
      The differential copper inducibility was mapped to sequences between -03 and -292
      upstream of the MT coding sequences. Expression of MTI is highly Cu-regulated,
      but this MT gene confers much less resistance than MTII genes.

PMID- 8750239
TI  - Nucleotide sequence of the GDS1 gene of Saccharomyces cerevisiae.
AB  - We have cloned and sequenced the GDS1 gene located on the right arm of chromosome
      XV of Saccharomyces cerevisiae. The gene codes for a 522 amino acid serine-rich
      protein with no obvious homology to proteins in the database. GDS1 gene was
      isolated as the multicopy suppressor of the glycerol-deficient phenotype caused
      by the nam9-1 mutation in the yeast nuclear gene encoding the mitochondrial
      ribosomal protein homologous to S4 proteins from various organisms. Disruption
      deletion of the GDS1 open reading frame leads to a partial impairment of growth
      on medium containing glycerol as the carbon source, indicating mitochondrial
      function of the gene product.

PMID- 8750240
TI  - The sequence of an 11.1 kb DNA fragment between ADH4 and ADE5 on the left arm of
      chromosome VII reveals the presence of eight open reading frames.
AB  - The complete sequence of a 11, 132 bp segment located on the left arm of
      chromosome VII of Saccharomyces cerevisiae has been determined and analysed.
      Eight open reading frames (ORFs) of at least 100 amino acids were identified.
      Five show similarities to known amino acid sequences. Another ORF encoding the
      chromosome segregation protein CSE1 is not entirely located in our sequenced
      fragment and is incomplete at its C-terminus. The two remaining ORFs do not
      display similarities to known sequences.

PMID- 8750241
TI  - Sequencing of an 18.8 kb fragment from Saccharomyces cerevisiae chromosome VI.
AB  - The nucleotide sequence of lambda phage clone 4121, which contains the 18.8 kb
      fragment of Saccharomyces cerevisiae chromosome VI left arm, was determined. This
      sequence had seven open reading frames (ORFs), four of which were identical to
      known genes (ACT1, YPT1, TUB2 and RPO41). Another three ORFs (4121orfR003,
      4121orfR004 and 4121orfRN001) were highly homologous to FET3 multi-copper
      oxidase, glucose transport protein, and hypothetical protein of YIL106w on
      chromosome IX, respectively. 4121orfRN01 is suggested to contain an intron.

PMID- 8750242
TI  - Molecular cloning and sequencing of the hcs gene, which encodes 3-hydroxy-3
      methylglutaryl coenzyme A synthase of Schizosaccharomyces pombe.
AB  - We have cloned and sequenced the hcs gene, which is thought to encode a 3-hydroxy
      3-methylglutaryl coenzyme A (HMG-CoA) synthase consisting of 447 amino acids,
      from the fission yeast Schizosaccharomyces pombe. The predicted amino acid
      sequence of the hcs product of S. pombe has homology with the HMG-CoA synthase of
      rat (47.8%), chicken (49.2%), hamster (47.1%) and human cells (46.9%). One of the
      hcs genes was replaced with a marker gene in the diploid cell. No viable hcs
      disrupted haploid was isolated after tetrad dissection, suggesting that the hcs
      gene is essential for growth. However the hcs-defective mutant could be grown on
      a medium containing 5 mg/ml mevalonate. These results strongly support that the
      hcs gene encodes HMG-CoA synthase and S. pombe contains a single copy of the hcs
      gene.

PMID- 8750243
TI  - Current awareness on yeast.

PMID- 8750244
TI  - Effects of pravastatin in heart transplant recipients: implications of
      Kobashigawa et al.
AB  - The recently published article by Kobashigawa et al. [1] regarding the benefit of
      using pravastatin in treating hypercholesterolemia in heart transplant recipients
      is reviewed. A comment on the implications of the researchers' findings follows.

PMID- 8750245
TI  - Reduction of coronary events: evidence from clinical trials.

PMID- 8750246
TI  - Lipid-lowering treatment: effects on endothelial dysfunction.
AB  - An association has been demonstrated between the extent of atherosclerotic
      involvement and vasodilatory capacity in coronary and cerebral circulation.
      Impairment of endothelium-dependent relaxation is inversely related to HDL
      concentrations in plasma. Angiographic studies in humans have shown improved
      vasodilation capacity of the coronary arteries after lipid-lowering treatment.

PMID- 8750247
TI  - Trials of the effects of drugs and hormones on lipids and lipoproteins.
AB  - Recent trials on the efficacy of drugs and hormones in lowering cholesterol and
      correcting lipoprotein profiles are reviewed. Emphasis is placed on the risk
      benefit ratio, which determines the clinical value of therapeutic regimens.
      Whereas 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors have set a
      standard for treatment of hyperlipidaemia, the role of hormone replacement
      therapy in postmenopausal women in the prevention of coronary artery disease has
      more recently become better defined.

PMID- 8750248
TI  - Selection of appropriate type and intensity of lipid-lowering therapy.
AB  - A wide consensus has been reached concerning the importance of lipid-lowering
      drug therapy in patients with dyslipidaemia with overt coronary heart disease.
      This consensus is also likely to be reflected in the more active treatment of
      other high-risk patient groups. The statin family of drugs has been tested in a
      large secondary prevention study, the Scandinavian Simvastatin Survival Study,
      and in angiographic trials. Their role in the treatment of hypercholesterolaemia
      and mixed hyperlipidaemia is increasing, whereas fibrates are increasingly
      limited to hypertriglyceridaemia.

PMID- 8750249
TI  - Trials of lipid-lowering therapy in primary prevention of coronary heart disease.
AB  - The effectiveness of lipid-regulating therapy in the primary prevention of
      coronary heart disease requires further investigation. The only data available
      are from trials conducted before the advent of more potent lipid-regulating
      agents, but several large trials currently in progress are expected to provide
      valuable evidence about the role of lipid-regulating intervention in primary
      prevention.

PMID- 8750250
TI  - Trials of lipid-lowering therapy in secondary prevention of coronary heart
      disease.
AB  - The Scandinavian Simvastatin Survival Study showed that a 35% decrease in LDL
      cholesterol was accompanied by a 42% reduction in coronary mortality. Even if the
      period of time is longer than 1 year for the divergence of survival curves in the
      simvastatin and placebo groups there are reasons to believe that the beneficial
      effect of lipid lowering is rapid. The effect may be mediated by stabilization of
      lipid-rich coronary lesions or by effects on endothelium. Lipid-lowering studies
      in the acute stage of coronary heart disease are suggested.

PMID- 8750251
TI  - Effects of lipid-lowering therapy on total and coronary mortality.
AB  - The results of several lipid-lowering randomized trials were released during the
      past year. The Scandinavian Simvastatin Survival Study has contributed
      significantly to the understanding of lipid-lowering on all-cause and coronary
      mortality outcome. An approximate 25% net difference in cholesterol between the
      simvastatin and placebo group produced a 30% reduction in total mortality in the
      simvastatin group (P < 0.01). No increase in noncardiovascular mortality or
      nonfatal diseases was observed. Although angiographic trials that study
      atherosclerosis are not designed to show the effect on clinical outcome, several
      new trials such as the Asymptomatic Carotid Artery Progression Study, the
      Multicentre Anti-Atheroma Study, the Canadian Coronary Atherosclerosis
      Intervention Trial and the Stanford Coronary Risk Intervention Project all add
      information that is consistent with the results from the Scandinavian Simvastatin
      Survival Study. The meta-analysis of randomized cholesterol-lowering trials also
      indicates that no excess of all-cause mortality is present when the degree of
      cholesterol reduction and treatment modality is adjusted. It is probable that the
      excess mortality from noncardiovascular causes found in unadjusted analyses is
      due to specific effects of hormones and fibrate drug treatments to reduce
      cholesterol. It is concluded that the lipid hypothesis is confirmed more solidly
      than ever before.

PMID- 8750252
TI  - Angiographic trials of lipid-lowering therapy: an update.
AB  - The value of specific LDL apheresis in drug-resistant cases of hyperlipidaemia is
      reviewed, as well as new data on the prevention of new lesion formation, efficacy
      of therapy based on initial lipid levels, and the consequences of lipid lowering
      in the angioplasty setting. Studies undertaken in the carotid and femoral bed are
      included, as is a brief discussion of the use of probucol as an adjunct to lipid
      lowering therapy. These studies have emerged on a backdrop of data focused more
      on reduction of clinical events than on morphologic changes. Studies on the
      clinical impact of lipid-lowering therapy are included to provide a linkage
      between the rationale and conclusions of the angiographic trials with the
      emerging demonstration that cholesterol lowering does indeed reduce both
      cardiovascular and total mortality without inducing significant noncardiovascular
      morbidity or mortality.

PMID- 8750253
TI  - Percentage change rather than plasma level of LDL-cholesterol determines
      therapeutic response in coronary heart disease.
AB  - We have analysed 11 trials which used quantitative angiography to assess the
      effects of lipid-lowering therapy on coronary atherosclerosis. Linear regression,
      weighted for the number of patients studied, showed that the change in per cent
      diameter stenosis was significantly correlated with per cent reduction in LDL
      cholesterol (r = 0.74, p < 0.0005), but not with the LDL-cholesterol
      concentration during the trials. These findings have important implications for
      the secondary prevention of coronary heart disease.

PMID- 8750254
TI  - Therapy and clinical trials.

PMID- 8750255
TI  - Nutrition.

PMID- 8750256
TI  - Genetics and molecular biology.

PMID- 8750257
TI  - Lipid metabolism.

PMID- 8750258
TI  - Hyperlipidaemia and cardiovascular disease.

PMID- 8750259
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 8750260
TI  - Therapy and clinical trials.

PMID- 8750261
TI  - Standards for specialist units undertaking blood and marrow stem cell transplants
      -recommendations from the EBMT. Accreditation Sub-Committee of the European Group
      for Blood and Marrow Transplantation (EBMT).

PMID- 8750262
TI  - Prevention of graft-versus-host disease with anti-CD5 ricin A chain immunotoxin
      after CD3-depleted HLA-nonidentical marrow transplantation in pediatric leukemia
      patients.
AB  - To determine if partial T cell depletion and intensive post-transplant
      immunosuppression is effective for the prevention of graft-versus-host disease
      (GVHD) in pediatric recipients of HLA-non-identical marrow transplants, 10
      children with leukemia received high-dose thiotepa, cyclophosphamide and total
      body irradiation followed by transplantation of CD3-depleted marrow from matched
      unrelated or one-antigen mismatched related adult donors. To maximize the number
      of stem cells infused, a large volume (1-1.51) of marrow was harvested from the
      donors. After immunopurging, the marrow infused contained a median of 3.7 x 10(6)
      CD34+ cells/kg, 1.4 x 10(6) CD3+ cells/kg, and 1.6 x 10(6) CD5+ cells/kg as
      assessed by flow cytometry. Cyclosporine, methylprednisolone and anti-CD4 ricin A
      chain immunotoxin (XZ-CD5) were used for prevention of GVHD post-transplant. All
      patients achieved an ANC > 0.5 x 10(9)/l. No patient developed capillary leak
      syndrome or renal failure from XZ-CD5. Five developed grade 2-4 acute GVHD, and
      all responded to treatment with steroids. Five of nine evaluable patients
      developed chronic GVHD. Two patients relapsed, but the most common cause of death
      was infection with or without chronic GVHD. Four patients survive 10+ to 27+
      months post-transplant. XZ-CD5 is well-tolerated in T cell-depleted marrow
      transplant recipients. However, partial T cell depletion and intensive post
      transplant immunosuppression did not prevent moderate acute GVHD or chronic GVHD.
      This may have been due to the high number of T cells infused with the marrow.

PMID- 8750263
TI  - Allogeneic bone marrow transplantation for primary myelofibrosis.
AB  - The published experience of allogeneic bone marrow transplantation for primary
      myelofibrosis (PMF) is limited. Three patients (24-49 years) with PMF received
      allogeneic marrow grafts from HLA-identical sibling donors after conditioning
      with 110 mg/m2 melphalan and 1050 cGy total-body irradiation (TBI). Donor marrow
      was not depleted of T cells, and graft-versus-host disease (GVHD) prophylaxis
      comprised cyclosporine and methotrexate. None of the patients was splenectomized
      prior to the transplant. Two patients received G-CSF post-transplant to hasten
      neutrophil recovery. One patient died of multi-organ failure 23 days post
      transplant. Hematopoietic recovery was relatively slow in the other two who had
      gradual resolution of the marrow fibrosis over several months. One of the two
      died of overwhelming pneumococcal sepsis within 2 weeks of stopping prophylactic
      penicillin 31 months post-transplant. The other patient is alive and well 20
      months post-transplant with a Karnofsky score of 100% and no fibrosis of the
      marrow. We conclude that PMF is correctable by allogeneic BMT. Hematologic
      recovery post-transplant is slow, but counts may normalize with time without the
      need for splenectomy.

PMID- 8750264
TI  - Risk factors for acute graft-versus-host disease in 291 consecutive HLA-identical
      bone marrow transplant recipients.
AB  - We analysed 35 risk factors for acute GVHD in 291 consecutive recipients of HLA
      identical sibling marrow transplants from 1975 to 1993. Of these, 16% developed
      moderate-to-severe acute GVHD following transplantation. In multivariate
      analysis, GVHD prophylaxis with monotherapy (MTX or CsA) (P = 0.015)
      seropositivity for several herpes viruses in the donor (P = 0.015) and
      seropositivity for CMV in the recipient (P = 0.037) before the transplants as
      well as early engraftment (P = 0.016), were the principal risk factors for GVHD.
      A high serum TNF-alpha level during conditioning therapy was also a significant
      risk factor in 75 recipients (P = 0.005). The risk of grades II-IV acute GVHD
      increased with the number of risk factors. Thus the cumulative incidence of acute
      GVHD was 1%, if no risk factor was present, 4% with one, 9% with two, 21% with
      three and 44% in patients with four risk factors. Factors reported to correlate
      with acute GVHD, such as age, diagnosis, female donor to male recipient, relative
      response and donor-responding capacity in MLC, MNS blood group antigen,
      splenectomy and bone marrow cell dose were not associated with acute GVHD in this
      study. Five-year survival was 24% in patients with grades II-IV GVHD vs 62% in
      patients with grades 0-I GVHD (P = 0.0001).

PMID- 8750265
TI  - Omission of day 11 methotrexate does not appear to influence the incidence of
      moderate to severe acute graft-versus-host disease, chronic graft-versus-host
      disease, relapse rate or survival after HLA-identical sibling bone marrow
      transplantation.
AB  - Sixty-five patients with haematological malignancy received high-dose
      chemotherapy or chemoradiotherapy followed by a T replete, HLA-identical sibling
      bone marrow transplant. All were scheduled to receive a standard
      cyclosporine/methotrexate immune suppressive regimen to minimise the risk of
      graft-versus-host disease post-transplant. Forty-six patients received all four
      scheduled doses of methotrexate, while in nineteen the day 11 dose was omitted
      due to marked oropharyngeal mucositis or febrile neutropenia. There was a slight
      increase in the incidence of acute graft-versus-host disease (GVHD) grades I-IV
      in those not receiving compared to those receiving day 11 methotrexate (84 vs 71%
      (P = 0.04)). However, there was no difference in the incidence of acute GVHD
      grades II-IV (14 vs 22%), in the incidence of chronic GVHD (38 vs 47%), in
      transplant-related mortality (21 vs 24%), in relapse rate (42 vs 51%), in 4-year
      survival (38 vs 48%), or in disease-free survival (38 vs 42%). These findings
      suggest that the day 11 methotrexate dose could be omitted without a major
      deleterious effect on the outcome of HLA-identical sibling marrow
      transplantation.

PMID- 8750266
TI  - Autografting for multiple myeloma: a 5-year experience at a single institution.
AB  - Over a 5-year period, we have performed 33 autologous bone marrow or PBPC
      transplantations for multiple myeloma. Nine patients were in complete remission
      and 24 in partial remission at time of transplantation. Conditioning regimens
      were BEM (BCNU, etoposide and melphalan) in 29, busulphan and cyclophosphamide in
      three and melphalan alone in one. Two patients (6%), died within 3 months of
      transplant-related mortality, seven (21.3%), died of disease progression at a
      median follow-up of 11 months (range 4-24). Twenty-four patients (72.7%) are
      alive at a median follow-up of 15 months (range 4-61). Of nine patients
      transplanted in CR, four have relapsed and are alive and five remain in CR. Of 24
      patients transplanted in PR, nine have died, six remain in PR, eight achieved CR
      and one has progressive disease. The overall median progression-free survival
      (PFS) is 31 months (95% CI = 20-42). For patients transplanted in PR the median
      PFS is 24 months (95% CI = 22-26), the median PFS for patients transplanted in CR
      has not yet been reached. The median PFS for patients achieving CR pre- or post
      transplantation was better than for patients neither achieving CR pre- nor post
      transplantation (P = 0.05). The median PFS was also significantly improved for
      patients requiring only primary therapy, compared to patients needing second-line
      therapy to achieve CR or stable PR prior to transplantation (31 vs 11 months, P =
      0.02).

PMID- 8750267
TI  - Addition of erythropoietin to granulocyte colony-stimulating factor after priming
      chemotherapy enhances hemopoietic progenitor mobilization.
AB  - Hemopoietic progenitor cell mobilization intended for autotransplantation is now
      feasible in many patients, following the administration of single cytokines (G
      CSF, GM-CSF, IL-3) or their combination. Erythropoietin (EPO) is a cytokine which
      showed an interesting activity also on non-erythroid progenitors, however the
      clinical relevance of this activity has not been sufficiently investigated yet.
      This retrospective study has attempted to assess the effectiveness of the
      combination of EPO plus G-CSF after priming chemotherapy to increase the number
      of blood progenitor cells, as compared to the results obtained by G-CSF alone.
      Thirty-four patients underwent priming chemotherapy followed by cytokine
      administration: 18 patients received G-CSF 5 micrograms/kg/day and 16 patients G
      CSF plus EPO 50 U/kg/day. The two groups were homogeneous as regards the main
      clinical characteristics which are thought to affect BPC mobilization. As for
      hemopoietic progenitor cell mobilization, we observed that the combination of EPO
      and G-CSF was more effective in comparison with G-CSF alone, with a median of 1.9
      fold for circulating MNC, 4.0-fold for CFU-GM, 4.7-fold for BFU-E and 2.8-fold
      increase for CD34+ cells. The results of apheresis collections revealed that the
      same group of patients showed better results for total blood progenitor cells/kg.
      The difference was statistically significant both for BPC mobilization and
      collection. Our findings suggest that EPO has a synergistic activity with G-CSF
      in mobilizing hemopoietic progenitors; the good results obtained, despite our
      pretreated patients, suggest that this cytokine combination has both biologic and
      clinical relevance.

PMID- 8750268
TI  - Long-term pulmonary sequelae after autologous bone marrow transplantation in
      children without total body irradiation.
AB  - We investigated the long-term pulmonary sequelae of 38 children surviving 3 to
      11.5 years (median 7 years) after high-dose chemotherapy (HDC) and autologous
      bone marrow transplantation (ABMT) without TBI. This cross-sectional study
      included patients with neuroblastoma (21), non-Hodgkin's lymphoma (7), Ewing's
      sarcoma (5), rhabdomyosarcoma (3), medulloblastoma (1) and ALL (1). They were
      asked and examined for clinical signs and underwent a physical examination with
      chest X-ray; 33/38 had pulmonary function tests (PFT) performed. No obstructive
      disease was found. Fifteen out of 32 evaluable PFT (47%) were abnormal with a
      pulmonary restrictive syndrome in 10, and borderline values in five patients.
      Four of these 15 patients were symptomatic with exertional dyspnea and two of
      four had abnormal chest X-rays. The etiology was mainly multifactorial,
      associating HDC with thoracic radiotherapy +/- scoliosis/kyphosis +/- previous
      thoracotomy +/- post-ABMT interstitial pneumonitis. Only 3/10 patients with a
      restrictive syndrome had HDC containing BCNU or busulfan as the only risk factor
      for lung disease. We conclude that the prevalence of late pulmonary sequelae
      after ABMT without TBI is moderate and rarely due to HDC alone, since most
      abnormal PFT can be explained by heavy pretreatment prior to ABMT. As symptoms
      are scarce even in advanced disease, repeated testing and very long-term follow
      up are needed.

PMID- 8750269
TI  - Human herpes virus-6 infection in marrow graft recipients: role in pathogenesis
      of graft-versus-host disease. Newcastle upon Tyne Bone Marrow Transport Group.
AB  - To investigate the hypothesis that target organ infection with human herpes virus
      6 (HHV-6) exacerbates the clinical severity of GVHD, skin and rectal biopsies
      from 34 allogeneic bone marrow transplant (BMT) recipients and 23 comparative
      autologous recipients were studied. Biopsies and heparinised blood samples were
      obtained from all patients prior to and at regular intervals after BMT, and
      whenever GVHD was suspected. HHV-6 antigen was detected in cryostat sections by
      immunohistochemistry, and HHV-6 DNA in peripheral blood leucocytes (PBL) and
      biopsies by nested PCR. Twenty-eight (90%) of the 31 patients who engrafted
      developed clinical GVHD, which was mild in five, moderately severe in nine and
      severe in 14. Overall, HHV-6 DNA was detected in PBl in 74% of autologous
      recipients and 76% of allogeneic recipients, and in biopsy tissue in 48% of autos
      and 71% of allos. However, HHV-6 DNA was detected in skin and/or rectal biopsies
      more frequently in allogeneic recipients with severe GVHD (92%) than in those
      with either moderate (55%) or mild GVHD (22%), suggesting an association (P =
      0.004) between HHV-6 DNA in biopsy tissue and GVHD severity. A significant linear
      trend (P = 0.03) was identified between detection of HHV-6 DNA in biopsy tissue
      obtained prior to or concomitant with the onset of GVHD and increased GVHD
      severity, suggesting that HHV-6 was causally linked to GVHD rather than
      reactivated as a consequence of GVHD therapy. Thus this study supports a role for
      HHV-6 in the initiation and/or exacerbation of GVHD, and suggests that the
      presence of HHV-6 DNA in the skin or rectum may be a factor in determining GVHD
      severity. If confirmed, these findings may have implications for the management
      of allogeneic BMT recipients.

PMID- 8750270
TI  - Various patterns of chimerism after allogeneic bone marrow transplantation for
      advanced chronic lymphocytic leukemia.
AB  - Chimerism studies after allogeneic BMT are performed to determine the donor
      and/or recipient origin of peripheral blood and marrow lymphoid and hematopoietic
      cells. These studies have been performed mostly in leukemias and aplastic anemia.
      We report DNA-based chimerism studies in three patients transplanted for advanced
      CLL from a histocompatible sibling. Following conditioning with chlorambucil,
      cyclophosphamide and TBI all three successfully engrafted. One has remained in
      continuous complete remission (CR) with a complete donor chimerism (CDC) for 110
      months post-BMT. Another was in mixed chimerism (MC) with minimal residual
      disease (MRD) at 3 months post-BMT but was in CR and in CDC at 6 months,
      suggesting that the persistent CLL cells has disappeared between these two
      studies. The third patient has been in persistent MC since BMT (24 months follow
      up), although he is in CR with no evidence of persistent CLL. We postulate that
      this patient's MC status is due to normal residual recipient lymphohematopoietic
      cells that survived the conditioning regimen. In conclusion, various patterns of
      chimerism can be observed in CLL patients after BMT while remaining in CR and
      with no evidence of residual CLL.

PMID- 8750271
TI  - Anti-body-dependent cellular cytotoxicity (ADCC) function of peripheral blood
      polymorphonuclear neutrophils (PMN) after autologous bone marrow transplantation
      (ABMT).
AB  - Rapid recovery of the number and function of polymorphonuclear neutrophils (PMN)
      is critical to recovery from bone marrow transplantation. Although it is
      relatively easy to measure PMN number recovery, the evaluation of the functional
      recovery of these cells has not been adequately examined. The ability of
      peripheral blood PMNs to perform antibody-dependent cellular cytotoxicity (ADCC)
      was assessed in 25 patients undergoing autologous bone marrow transplantation
      (ABMT). PMNs were evaluated at a single cell level for ADCC function as measured
      by their ability to form plaques in antibody-sensitized ox erythrocyte (oxE)
      monolayers. The PMNs demonstrated low or absent ADCC function in the first week
      after completion of high-dose chemotherapy, regardless of primary diagnoses or
      myeloablative regimens. Although recovery to a neutrophil count of
      500/microliters was prolonged in patients with AML (mean 40.2 days; range 25-67
      days), functional activity of PMNs appeared much earlier (mean 19.6 +/- 6.1 days;
      range 2-65 days) in this group of patients compared to the group of patients with
      other diagnoses in which recovery to a neutrophil count of 500/microliters and
      the recovery of functional activity of PMNs occurred at roughly the same time.
      This single cell assay provided a useful method for determining ADCC functional
      ability of recovering PMNs post-BMT since few cells were required for each assay.
      This approach may also be useful in determining optimal timing of immune
      therapies post-ABMT, relying on myeloid cells as effector cells.

PMID- 8750272
TI  - Erythrocyte repopulation after major ABO incompatible transplantation with
      lymphocyte-depleted bone marrow.
AB  - Forty-four out of 258 allogeneic BMT were performed across the major ABO barrier.
      Donor erythrocyte repopulation could be evaluated in 30 cases. Fifty-eight
      patients transplanted with an ABO compatible or minor incompatible graft served
      as the control group. All patients received a marrow graft depleted of
      lymphocytes by counterflow centrifugation. Less than 10(8) residual erythrocytes
      were present in the graft. Cyclosporin A was used as immunoprophylaxis after
      transplantation. Erythrocyte repopulation was measured using a fluorescent
      microsphere method. An adapted transfusion policy was applied. Eight out of 30
      patients (27%) with major ABO incompatibility had no detectable donor
      erythrocytes 2 months after BMT. Up to 3 months after BMT donor erythrocyte
      repopulation was significantly delayed in the ABO incompatible group (P < or =
      0.03). Significantly more erythrocyte transfusions were required in the ABO
      incompatible group (P < 0.001). Six patients with blood group O (20%) developed
      pure red cell aplasia which resolved in five without therapeutic intervention. In
      these six patients anti-A antibody titers were persistently high the first 3
      months after BMT. This was in contrast with 22 patients with timely recovery of
      erythropoiesis in whom anti-A and anti-B antibody titers showed a steady decrease
      after BMT. The incidence of immunohematological complications in these patients
      who received a lymphocyte depleted major ABO incompatible graft is similar (20%)
      to the incidence reported in the literature. Serious morbidity related to major
      ABO incompatibility did not occur.

PMID- 8750273
TI  - T cell reconstitution by haploidentical BMT does not restore the diversification
      of the Ig heavy chain gene in patients with X-linked SCID.
AB  - We previously examined the Ig heavy (H) chain gene of pretransplant patients with
      X-linked SCID (XSCID), having defects in the gene of the IL-2 receptor (R) gamma
      chain. In the present study, we analyzed two post-transplant XSCID patients, in
      whom T cell-depleted haploidentical BMT resulted in lymphoid split chimeras,
      i.e., donor functional T cells coexisting with recipient B cells. Although the
      recipient B cells produced IgM, no isohemagglutinin or Ag-specific Ab was
      detected. To investigate the cause of failure to produce Ab in the patients, we
      sequenced the complementarity determining region 3 (CDR3) and adjacent region of
      Ig H chain gene, which govern Ab specificity. Among the 64 post-transplant CDR3
      junctional sequences, combinatorial and junctional diversity were normal compared
      with those in age-matched controls. All of the post-transplant joining regions
      except one clone were equal to germline and the frequency of somatic mutation was
      significantly lower than that in age-matched controls. The results indicated that
      T cell reconstitution by BMT does not restore diversification of the Ig gene in
      the IL-2R gamma chain-deficient B cells, which might be associated with the
      defect in the Ag-specific Ab production.

PMID- 8750274
TI  - Specific T and B cell immunity to measles after allogeneic and autologous bone
      marrow transplantation.
AB  - Lymphocyte stimulation with measles virus antigen (MLY) and ELISA for measles IgG
      antibodies were performed on 60 patients after allogeneic bone marrow
      transplantation (BMT), and on 59 patients after autologous bone marrow
      transplantation (ABMT). The T cell response was significantly higher in the 75
      measles seropositive patients than in the 29 seronegative patients (P < 0.001),
      but not significantly different from the MLY in the 15 patients with uncertain
      serologic reactivity. When the patient group was divided according to type of
      transplant, the T cell response to measles was also significantly higher in
      seropositive patients than in seronegative patients after both ABMT (P < 0.001)
      and after BMT (P < 0.05). Twenty-three seronegative children who were measles
      vaccinated after BMT had a significantly higher T cell response to measles (7100
      c.p.m.) than 17 seronegative non-vaccinated children (100 c.p.m.; P < 0.01). No
      significant difference was seen in the T cell response in 12 seronegative
      children vaccinated after ABMT (2500 c.p.m.) compared to seven children not
      vaccinated (2800 c.p.m.; NS). Seroconversion after vaccination was more frequent
      in children after BMT (20/23; 87%) compared to ABMT (5/12; 42%; P < 0.05) but no
      significant difference was found in the T cell response. Therefore, most patients
      who lost IgG antibodies to measles after bone marrow transplantation also lost
      their T cell response to measles. A T cell response to measles developed in most
      patients who seroconverted after vaccination. Failure to develop antibodies to
      measles in ABMT patients after revaccination may depend on a persisting T cell
      immunity.

PMID- 8750275
TI  - Detection of tumor cells in the bone marrow of stage IV breast cancer patients
      receiving high-dose chemotherapy: the role of induction chemotherapy.
AB  - High-dose chemotherapy and hematopoietic support can produce long-term, disease
      free remissions in selected patients with metastatic breast cancer. Occult bone
      marrow involvement may contribute to late relapse. We used five anti-breast
      cancer monoclonal antibodies and flow cytometry with cytological analysis of
      sorted immunostained cells to detect tumor cells in the bone marrow in two
      cohorts of patients. The first (Upfront) cohort was treated with a single course
      of high-dose chemotherapy and autologous bone marrow support (ABMS) without
      induction chemotherapy. The second (AFM) cohort received induction chemotherapy
      with doxorubicin, 5-fluorouracil and methotrexate prior to high-dose chemotherapy
      and ABMS. Of the 15 Upfront patients, seven (47%) had immunostained cells in the
      harvested bone marrow by flow cytometry and 8/15 (53%) had positive cytologies.
      Of the 49 AFM patients studied, nine (18%) had immunostained cells in the bone
      marrow, and only 1/49 (2%) had positive cytologies. Induction chemotherapy
      significantly decreased bone marrow contamination as detected by flow cytometry
      and cytology in patients with breast cancer. The detection of immunostained cells
      in the bone marrow did not predict for relapse or overall survival.

PMID- 8750276
TI  - Detection of minimal residual disease and persistence of host-type hematopoiesis:
      a study in 28 patients after sex-mismatched, non-T cell-depleted allogeneic bone
      marrow transplantation for Philadelphia-chromosome positive chronic myelogenous
      leukemia.
AB  - We investigated the persistence of host-type hematopoiesis as defined by mixed
      chimerism (MC) in 28 male patients with chronic myelogenous leukemia (CML) who
      underwent opposite sex, non-T cell-depleted bone marrow transplantation (BMT) by
      amplification of Y-chromosome specific sequences, and correlated these results
      with the detection of minimal residual disease (MRD) by BCR/ABL mRNA
      amplification. Patients were studied at two time periods (> 3 months and > 24
      months post-BMT). All but two patients were conditioned with total body
      irradiation (TBI) and cyclophosphamide (CY). One patient received busulfan (Bu),
      thiothepa (Thio) and CY, another patient CY and Bu. Detection of MRD occurred
      exclusively among patients with a MC (significance P < 0.04). Six of 18 patients
      with MC had detectable MRD, four of these consecutively developed cytogenetic and
      hematological relapse. Of 28 patients studied more than 3 months post-transplant,
      18 (64%) had mixed chimerism and 10 (36%) had exclusively donor-derived blood
      cells. Nineteen patients were followed for their chimeric status between 24
      months and 136 months post-BMT. Four patients converted from MC to complete
      chimerism and 10 patients (53%) remained mixed chimeric. The high incidence of MC
      in patients who underwent BMT without T cell depletion was measured by using a
      PCR assay with a sensitivity of 0.001%. As previously described by other
      investigators patients with complete chimerism developed more acute GVHD grade I
      II (seven of 10 patients (70%) than patients with MC (nine of 18 patients (50%),
      not significant). This study also suggests that chimeric status might depend upon
      the regimen to prevent GVHD. One of four patients who received weekly
      methotrexate as GVHD prophylaxis developed MC, whereas in 11 of 18 patients
      receiving short course methotrexate and cyclosporine MC was detectable. All of
      six patients, prophylactically treated with a murine monoclonal antibody directed
      to the human alpha/beta T cell receptor in combination with cyclosporine, were
      mixed chimeras.

PMID- 8750277
TI  - Detection of clonal immunoglobulin gene rearrangements in the PBPC harvests of
      patients with acute lymphoblastic leukaemia.
AB  - We have used a fluorescently based PCR technique to detect rearrangements in the
      immunoglobulin heavy chain (IgH) gene in the presentation BM of five patients
      with adult ALL and have looked for similar rearrangements in their PBPC. Using
      this approach we have been able to demonstrate clonal rearrangements in the PBPC
      of two of five patients. Remission BM samples taken 6-12 weeks prior to
      leucapheresis failed to show a clonal rearrangement in either patient. The
      significance of these results is discussed.

PMID- 8750278
TI  - Effect of marrow processing on hematopoietic cell recovery in bone marrow
      harvests: focus on filtration.
AB  - Bone marrow processing requires a first step of filtration to remove small clots,
      bone fragments, fat cells and fibrin followed by centrifugation to separate
      mononuclear cells (MNC). These procedures cause a significant loss of cells
      potentially including hematopoietic stem cells (HSC). We therefore analyzed the
      cell recovery and phenotype of various fractions (whole marrow; filtered marrow;
      MNC collected after centrifugation; bone marrow fragments trapped by filtration)
      of bone marrow harvests (BMH) from patients with different hematological
      malignancies undergoing autologous bone marrow transplantation. Analysis of 25
      BMH showed that the mean percentage of WBC and MNC recovered after filtration was
      respectively 92.28 +/- 7.42% and 92.3 +/- 9.05% of the original BMH while after
      centrifugation the percentage was 20.23 +/- 6.47% and 75.7 +/- 12.81%. The
      percentage of cells present in the tissue fragments trapped in the filters
      obtained from five BMH was only 3.93 +/- 1.25% (WBC) and 5.65 +/- 2.2% (MNC) of
      those originally present in the harvest. Phenotypic analysis performed on the
      same samples showed that there is no selective loss of MNC or CD34+ cells in the
      filtration process. Our data indicate that processing of BMH, in particular
      filtration of tissue fragments, does not affect the recovery of HSC.

PMID- 8750279
TI  - Allogenic peripheral blood stem cell (PBSC) transplantation in two patients with
      graft failure.
AB  - Allogenic peripheral blood stem cells (PBSC) were used for graft failure after
      BMT in two patients. These PBSC were mobilized by G-CSF in the same donors,
      harvested and given without reconditioning to the patients. In one patient, PBSC
      with a very high T cell number were given unprocessed, in the other patient,
      CD34+ cells were positively enriched due to a 2-antigen difference. None of the
      patients had hyperacute GVHD. Trilineage engraftment was seen after 13 days.
      Acute GVHD grade II to III developed on days +31 in patient 1 and +16 in patient
      2, involving predominantly gut and liver, but sparing the skin. Thus, allogeneic
      PBSCT for graft failure did not cause hyperacute GVHD even with very high T cell
      numbers in patient 1, and graft failure with CD34 selected PBSC was successfully
      reversed even with a low number of T cells in patient 2.

PMID- 8750280
TI  - Severe migratory polyarthritis following in vivo CAMPATH-1G.
AB  - CAMPATH-1G is an IgG2b rat antihuman (CDw52) monoclonal antibody (MoAb) which is
      currently being used for T cell depletion in the setting of allogeneic bone
      marrow transplantation (BMT). In addition it elicits substantial lymphoid
      depletion, an effect which is being explored for remission induction in patients
      with lymphoid malignancies and for treating patients with various autoimmune
      disorders, in particular rheumatoid arthritis. Recently, in vivo CAMPATH-1G has
      been introduced to achieve increased immunosuppression in the pretransplant
      conditioning, for prevention of graft rejection following T cell depleted BMT.
      Here we describe a patient with T cell lymphoblastic lymphoma who received in
      vivo CAMPATH-1G as part of the pretransplant conditioning regimen and who, 6 days
      after the first dose, developed severe migratory polyarthritis. This is the first
      report of severe migratory polyarthritis as a very unusual complication following
      CAMPATH-1G MoAb administration.

PMID- 8750281
TI  - Successful bone marrow transplantation in a child with combined IgG subclass
      deficiency and neutropenia.
AB  - An 8-year-old boy with combined IgG1 deficiency and neutropenia underwent
      allogeneic BMT from his HLA-identical, MLC-negative sister, because
      immunoglobulin (Ig) infusions and prophylactic antibiotics failed to prevent life
      threatening infections. Conditioning was with busulfan and cyclophosphamide, MTX
      and CYA were given for the prophylaxis of GVHD. For 16 months after BMT no
      serious infections have occurred and serum IgG1 levels have returned to the
      normal range without Ig replacement. BMT may be appropriate treatment for
      patients with IgG subclass deficiency who rarely respond to conservative therapy.

PMID- 8750282
TI  - Invasive Candida guilliermondii infection: in vitro susceptibility studies and
      molecular analysis.
AB  - Candida guilliermondii is rarely isolated from humans. We describe a case of
      disseminated C. guilliermondii with associated purulent pericarditis, despite
      high-dose amphotericin B (AmB), in a 19-year-old female with aplastic anemia who
      underwent BMT. In vitro susceptibility studies of the 13 clinical isolates, two
      control strains and one environmental isolate revealed a minimum inhibitory
      concentration (MIC) range of (0.19-1.56 micrograms/ml) for AmB and (1.25-10
      micrograms/ml) for fluconazole. Pulsed-field gradient gel electrophoresis was
      performed to evaluate possible similarities between strains. This case is
      significant for several reasons, the high degree and prolonged duration of
      fungemia despite high-dose AmB and concomitant flucytosine, the change in in
      vitro susceptibility during therapy, the initial misidentification of the yeast
      isolate, and the invasiveness of the organism. The poor response to therapy may
      have been due to the severe and sustained neutropenia and the high MICs of C.
      guilliermondii to AmB.

PMID- 8750283
TI  - CD34+ cell subsets and platelet recovery after PBSC autograft.

PMID- 8750284
TI  - Transplantation with peripheral blood stem cells from unrelated donors without
      serious graft-versus-host disease.

PMID- 8750285
TI  - Hair growth after GVHD induction in BALB/c nude mice.

PMID- 8750286
TI  - Phase I study of high-dose ifosfamide, carboplatin and etoposide with autologous
      hematopoietic stem cell support.

PMID- 8750287
TI  - BMT for isolated central nervous system relapse in children with ALL.

PMID- 8750288
TI  - Ultrasonography in pregnancy and fetal abnormalities: screening or diagnostic
      test? IPIMC 1986-1990 register data. Indagine Policentrica Italiana sulle
      Malformazioni Congenite.
AB  - The aim of the present study was to assess the sensitivity of ultrasound
      diagnosis used as a screening test in detecting major congenital anomalies in the
      prenatal period in a large nation-based multicentre setting. Data from the IPIMC
      register were collected in the period 1986-1990. One hundred and thirty-five
      hospitals, located in 17 out of the 20 regions in Italy, participated in the
      register. Study cases were 3479 infants with major congenital anomalies diagnosed
      at birth or in the first week of life. Subjects with chromosomal anomalies or
      multiple defects were excluded. The sensitivity of ultrasound prenatal diagnosis
      was 49.5 per cent for central nervous system anomalies, 3.8 per cent for
      congenital heart diseases, 17.1 per cent for gastrointestinal tract defects, 46.6
      per cent for abdominal wall defects, 74.8 per cent for urinary tract anomalies,
      and 22.9 per cent for skeletal abnormalities. The detection rate for
      diaphragmatic hernia was 24.2 per cent. Overall, only 18 per cent of the defects
      diagnosed in utero were detected before 24 weeks' gestation. The sensitivity of
      prenatal diagnosis was 30.1 and 19.0 per cent in the northern, central, and
      southern regions, respectively. In light of its low sensitivity, ultrasonography
      as a screening test in the general population should be abandoned, although some
      improvement in its performance should be expected following adequate training of
      the ultrasound staff and the use of good technical equipment.

PMID- 8750289
TI  - Prevalence and clinical significance of anticardiolipin antibodies in pregnancies
      complicated by parvovirus B19 infection.
AB  - Anticardiolipin antibodies were measured in 60 pregnant women with acute
      parvovirus B19 infection. Test results for eight (13.3 per cent) women were
      positive for anticardiolipin antibody. Six of these eight women became negative
      later, yielding a prevalence of anticardiolipin antibodies of 3.3 per cent (2/60)
      6 months after acute parvovirus B19 infection. Anticardiolipin antibody
      positivity was not associated with an increased risk of abortion, fetal death, or
      maternal complications. This study suggests that there is an elevated frequency
      of anticardiolipin antibodies in pregnant women with acute parvovirus B19,
      probably representing an epiphenomenon. However, this is not associated with an
      adverse maternal or perinatal outcome.

PMID- 8750290
TI  - Prenatal identification of i(Yp) by molecular cytogenetic analysis.
AB  - An i(Yp) is a rare marker chromosome. We present a case of de novo 46,X,i(Yp)
      detected prenatally in an amniotic fluid specimen. Fluorescence in situ
      hybridization (FISH) studies using a panel of Y-specific biotinylated DNA probes
      identified the marker chromosome as i(Yp). Comparative genomic hybridization
      (CGH) studies further confirmed the diagnosis. Upon pregnancy termination,
      external examination of the fetus revealed a generally well-developed male fetus
      with slight facial dysmorphism and prominent rocker-bottom feet. The molecular
      cytogenetic data in this case proved very useful in genetic counselling and
      served as a good example illustrating the important role of molecular techniques
      for accurate identification of marker chromosomes.

PMID- 8750291
TI  - Elevated alpha-fetoprotein and human chorionic gonadotropin as a marker for
      placental trisomy 16 in the second trimester?
AB  - In a series of 2961 consecutive cases with second-trimester biochemical triple
      screening for Down's syndrome and neural tube defect (NTD), ten (0.3 per cent)
      showed an apparent increased risk for both conditions. Three cases had
      chromosomal abnormalities, namely trisomy 16 confined to the placenta. Since
      placental trisomy 16 as well as cases with increased alpha-fetoprotein (AFP) and
      human chorionic gonadotropin (hCG) are associated with (intrauterine growth
      retardation (IUGR), oligohydramnios, and fetal demise, at least some cases with
      this atypical biochemical profile could be explained by this chromosomal
      abnormality. From our results we recommend that in cases with increased risk for
      both Down's syndrome and NTD, fetal karyotyping should preferably be done on a
      placental biopsy, especially when ultrasound in the absence of anomalies
      demonstrates early IUGR.

PMID- 8750292
TI  - Repeat maternal serum testing for Down's syndrome screening using multiple
      markers with special reference to free alpha and free beta-hCG.
AB  - To determine the effect of routine repeat testing in serum screening for Down's
      syndrome, we compared estimates of the detection and false-positive rates. Five
      serum markers were measured--alpha-fetoprotein (AFP), unconjugated oestriol
      (uE3), human chorionic gonadotrophin (hCG), and its two subunits, free alpha and
      free beta-hCG. First and repeat test marker levels were available from 142 women
      whose samples had been routinely collected and stored in an antenatal serum bank.
      Different repeat testing policies were compared for various combinations of the
      markers. If all women had repeat tests using the four markers AFP, uE3, and free
      alpha and free beta-hCG, the detection rate for a 5 per cent false-positive rate
      was 69 per cent compared with 65 per cent if no women were repeated. Policies of
      repeating selected women gave similar results. The small gain in screening
      performance with repeat testing performed routinely is not worthwhile. If a woman
      does happen to have a repeat test, her risk estimate should, however, be based on
      both results, not just the second.

PMID- 8750293
TI  - Enhanced twin pregnancy detection within an open neural tube defect and Down
      syndrome screening protocol using free-beta hCG and AFP.
AB  - We have applied our multimarker approach of maternal serum alpha-fetoprotein
      (AFP) and free-beta human chorionic gonadotropin (hCG) for Down syndrome
      screening to multiple gestations to assess its efficacy for improved detection of
      twin and triplet pregnancies. This study matched 225 cases of twin pregnancy and
      39 cases of triplet pregnancy each with ten singleton pregnancies based on
      gestational week, race, time to receive sample, time of year of sample, and
      geographical area. The ratios of the MOM for each group at the tenth, 50th, and
      90th percentiles were compared by the Wilcoxon test. Risks for twins were
      calculated using Bayes' rule, the age-related incidence of twins, and the levels
      of AFP and free-beta hCG. The tenth, 50th and 90th percentiles of free-beta hCG
      MOMs in twin and triplet cases were 0.85, 1.99, and 4.51, and 1.38, 2.78, and
      4.07, respectively. For AFP, the MOMs at these percentiles were 1.26, 1.91, and
      2.99, and 2.02, 2.68, and 5.30, respectively. The twin and triplet distributions
      for each marker were statistically significantly different from the singleton
      distributions (P < 0.0001) and from each other (P = 0.0012). At a twin risk cut
      off of 1 in 50, 77.4 per cent of all twin gestations can be detected in a second
      trimester AFP and free-beta hCG screening protocol with 5.1 per cent of singleton
      pregnancies falsely identified as at risk for twins. Our dual marker protocol for
      mid-trimester pregnancy screening combining AFP and free-beta hCG can identify
      over 77 per cent of twin pregnancies in women less than 35 years of age. This
      benefit may contribute to an improved outcome of pregnancy by early detection of
      multiple gestation.

PMID- 8750294
TI  - Confined placental mosaicism in term placentae: analysis of 125 cases.
AB  - In order to determine the incidence of confined placental mosaicism (CPM) in term
      placentae and to show the presence of specific sites and the effect on fetal
      development, 125 placentae from uneventful pregnancies were analysed by
      cytogenetic methods. The incidence was at least 4.8 per cent and there were no
      specific sites on the placenta. Although the number of cases is still too small,
      we found CPM to be associated with intrauterine growth retardation in six cases.

PMID- 8750295
TI  - Immunohistochemical characterization of cells retrieved by transcervical sampling
      in early pregnancy.
AB  - Trophoblastic cells can be retrieved from the endocervix and the lower uterine
      segment in early pregnancy by aspiration or lavage (Rodeck et al., 1995). The
      feasibility of using this technique for prenatal diagnosis depends on how
      frequently fetal cells can be retrieved and whether such cells can be purified
      from the predominant maternal cell population. In this study, specimens retrieved
      from the lower uterine segment prior to elective first-trimester termination of
      pregnancy were examined histologically and characterized using a panel of
      monoclonal antibodies in an avidin-biotin-peroxidase technique. Lavage samples
      generally contained fewer cervical epithelial cells than aspirates. Syncytial
      fragments or cytotrophoblast were identified in 9 of 12 lavage samples but in
      only 4 of 10 aspirates. Trophoblast cells were reactive with various anti
      trophoblast monoclonal antibodies but the trophoblast cells present displayed
      considerable antigenic heterogeneity. For positive selection of trophoblast cells
      from these samples, it is likely that the best yield will be achieved by using a
      panel of carefully characterized monoclonal antibodies directed against various
      villous and extravillous trophoblast populations.

PMID- 8750296
TI  - Prenatal diagnosis of mosaic tetrasomy 12p/trisomy 12p by fluorescent in situ
      hybridization in amniotic fluid cells: a case report of Pallister-Killian
      syndrome.
AB  - A prenatally detected case of a rare mosaic tetrasomy 12p/trisomy 12p is
      reported, presenting as the well-known accessory isochromosome 12p and a
      supernumerary single 12p marker in 17/24 and 6/24 clones of cultured amniotic
      fluid cells, respectively. The chromosomal nature of both marker chromosomes was
      investigated in cultured amniotic fluid cells by fluorescent in situ
      hybridization with various probes: the 12-centromeric probes p alpha 12H8 and
      D12Z3, a whole chromosome 12 paint, and the chromosome 12p-specific paint M28.
      DNA analysis revealed a maternal origin of the extra 12p material. After
      counselling, the parents requested termination of pregnancy. Inspection and
      autopsy of the fetus revealed many of the dysmorphisms and internal structural
      abnormalities of the Pallister-Killian syndrome.

PMID- 8750297
TI  - Prenatal diagnosis of acute bladder distension associated with fetal
      sacrococcygeal teratoma--a case report.
AB  - A case report of sacrococcygeal teratoma prenatally diagnosed at 23 weeks of
      amenorrhea, subsequently causing dilatation of both lower and upper urinary
      tracts is presented. The importance of repeated ultrasonographic evaluation of
      fetuses with sacrococcygeal teratoma is discussed.

PMID- 8750298
TI  - Paralytic ileus in a fetus-neonate after maternal intake of benzodiazepine.
AB  - Paralytic ileus of the small bowel was diagnosed in a fetus at 32 weeks'
      gestation after referral because of polyhydramnios. The mother had taken
      clonazepam, a benzodiazepine, and carbamazepine during the entire pregnancy for
      epilepsy. All known causes for the ileus were ruled out and at 20 months the boy
      has developed normally. We conclude that maternal anticonvulsant drug intake was
      very likely the cause of the paralytic ileus. This side-effect is known in
      experimental and clinical pharmacology but has not yet been described in human
      fetuses.

PMID- 8750299
TI  - First-trimester diagnosis of Meckel-Gruber syndrome by transabdominal sonography
      in a low-risk case.
AB  - Meckel-Gruber syndrome is a rare autosomal recessive disorder often resulting in
      neonatal death within a few hours of life. The condition is usually diagnosed
      ultrasonographically in the second trimester and earlier diagnosis has been
      mainly confined to high recurrence risk pregnancies. We describe the earliest non
      invasive diagnosis of this condition at 12+2 weeks' gestation in a patient with
      no previous history using transabdominal ultrasound. Pregnancy termination was
      declined. Subsequent development of anhydramnios in the mid-trimester resulted in
      poor fetal visualization. We propose that first-trimester diagnosis of this
      condition is not only possible but preferable, as normal liquor volume
      facilitates visualization of fetal anatomy.

PMID- 8750300
TI  - Recurrent congenital toxoplasmosis in a woman with lupus erythematosus.
AB  - We describe the case of a patient with systemic lupus erythematosus, treated by
      corticosteroids, who presented during two successive pregnancies with serological
      reactivation of toxoplasmosis associated with fetal lesions. The first infected
      fetus died in utero with signs of hydrops. The second fetus was treated in utero
      with a combination of sulfadoxine and pyrimethamine, administered to the mother,
      and is now well. The increasing number of immunocompromised pregnant patients
      with immunity to Toxoplasma gondii may lead to a higher risk of reactivation of
      maternal toxoplasmosis and congenital infection.

PMID- 8750301
TI  - Prenatal diagnosis of Marfan syndrome: identification of a fibrillin-1 mutation
      in chorionic villus sample.
AB  - Marfan syndrome (MFS) is one of the most common heritable connective tissue
      disorders and is caused by mutations in a gene coding for fibrillin-1. All but
      one of over 30 published mutations have been unique and specific prenatal
      diagnostics can only be provided to families with a previously established
      mutation. We have earlier identified a 366 bp deletion of fibrillin mRNA in a
      three-generation British Marfan family. An affected female in the family together
      with her husband sought prenatal diagnosis. Chorionic villus sampling was
      performed at 11.5 weeks of gestation and total RNA was directly extracted from
      the sample. After reverse transcription and polymerase chain reaction (PCR) of
      the cDNA, the same deletion was identified in the chorionic villus sample (CVS)
      and the mother's sample in agarose gel electrophoresis. The fetal origin of the
      CVS was confirmed with polymorphic markers. In addition to the mutation analysis,
      CVS cells of the proband and a control fetus were cultured for biochemical
      studies of fibrillin polypeptides. The results of the biochemical investigation
      were in concordance with the molecular analysis.

PMID- 8750302
TI  - Detection of low-grade mosaicism in fetal cells isolated from maternal blood.
AB  - Recovering and analysing fetal erythrocytes from maternal blood is being pursued
      for non-invasive prenatal genetic diagnosis. We report the observation of
      46,XY/47,XXY mosaicism in fetal cells from a woman whose first-trimester
      chorionic villus sampling (CVS) initially showed only 46,XY. Only after
      exhaustive (500 cells) analysis were four XXY cells found in cultured villi.

PMID- 8750303
TI  - Prenatal molecular diagnosis of Gaucher disease.
AB  - Prenatal diagnosis of Gaucher disease, the most prevalent glycolipid storage
      disease, is based on a reliable enzyme assay of cells from amniocentesis or
      chorionic villous samples. However, this method cannot differentiate among the
      various forms of the disease. This report details four cases of prenatal
      diagnosis of Gaucher disease, three of which predate the use of molecular
      diagnosis. DNA mutation analysis to determine the genotype was predictive of the
      phenotypic status of the fetus and conformed to the genotype of an affected
      proband where available.

PMID- 8750304
TI  - The ultrasonic detection of an isolated craniosynostosis.
AB  - The prenatal detection of scaphocephaly, an isolated form of craniosynostosis, is
      presented. The diagnosis was made at 34 weeks of gestation in a woman with
      polyhydramnios. The ultrasound appearance and postnatal follow-up are presented.

PMID- 8750305
TI  - Inter-observer discrepancy in scoring signals on interphase FISH with an X
      library probe illustrated in a case of 47,XXX.

PMID- 8750306
TI  - Difficulties in prenatal detection of mosaic trisomy 8.

PMID- 8750307
TI  - Current awareness in prenatal diagnosis.

PMID- 8750308
TI  - Secondary prevention of allergic disease: an adjunct to primary prevention.

PMID- 8750309
TI  - Genetics of atopy.

PMID- 8750310
TI  - Glucocorticoids and growth in asthmatic children.
AB  - The effects of asthma and oral and inhaled glucocorticoid therapy on growth in
      children are reviewed. Previous reports have shown that asthma itself may delay
      the onset of puberty, an effect which may masquerade as growth suppression. Oral
      glucocorticoids appear to impair growth; however, lower doses and alternate-day
      therapy may have less risk of this effect. While a controversial topic, inhaled
      glucocorticoids in lower doses appear to be associated with a small risk of
      adverse effects on growth. Minimal data are available for higher doses.
      Knemometry, a relatively new technique used for measuring small changes in
      growth, has detected short-term effects with both oral and inhaled
      glucocorticoids therapy. However, a number of limitations are associated with
      short-term growth studies. Clinicians should be aware of the potential for growth
      impairment with glucocorticoid therapy so adequate monitoring can be undertaken
      and appropriate intervention introduced when deemed necessary.

PMID- 8750311
TI  - Leukotriene B4 and C4 generation by human leukocytes after ex vivo stimulation
      with Ca-ionophore and opsonized zymosan in children with atopic asthma.
AB  - The ex vivo release of leukotriene B4 (LTB4) and leukotriene C4 (LTC4) from
      leukocytes was evaluated after stimulation with both Ca-ionophore (Ca-I) and
      opsonized zymosan (OZ) in children with atopic asthma. Twenty-seven patients with
      asthma of varying severity were evaluated and divided into three groups: 1)
      moderate to severe asthma using inhaled steroids and symptom-free for the last 3
      weeks (n = 8), 2) mild asthma with sporadic symptoms, only using inhaled beta 2
      agonists < 3 times/week (n = 8), and 3) acute asthmatic attacks admitted to
      hospital (n = 11). A group of children without atopic disease or any other known
      disease served as controls (n = 15). Total serum IgE levels were significantly
      increased in the children with asthma compared with the control group. LTC4
      production was only significantly increased in the group of children with
      moderate to severe asthma after stimulation with Ca-I, when compared with
      controls. In the same group, a trend towards increased LTC4 production after
      stimulation with OZ was found. LTB4 was not significantly increased in any
      patient group compared with the control group. A significant correlation between
      LTC4 production after stimulation with Ca-I, but not OZ, and the relative blood
      eosinophil count was found in all subjects. LTC4 generation per eosinophilic cell
      after stimulation with Ca-I or OZ was not statistically different in any patient
      group compared with the controls. We conclude that the increased leukotriene (LT)
      levels found after the stimulation of peripheral white blood cells sampled from
      atopic children with asthma are mainly the result of increased numbers of LT
      producing cells, rather than due to increased releasability from these cells.

PMID- 8750312
TI  - Lack of correlation between NADPH-oxidase priming and elevated alkaline
      phosphatase activity in cord blood neutrophils.
AB  - Human neutrophils were isolated from cord blood drawn after Caesarean section
      deliveries without labour and from peripheral blood from healthy adults. The
      alkaline phosphatase (ALP) activity in the cell populations was compared with the
      release of respiratory burst products after activation with the chemoattractant n
      formyl-methionyl-leucyl-phenylalanine (fMLP). In contrast to cord blood
      neutrophils obtained from babies after normal vaginal deliveries, the Caesarean
      section neutrophils were not metabolically primed. However, like the neutrophils
      from vaginally delivered babies, the Caesarean section neutrophils showed an
      increased ALP activity compared to adult control neutrophils. These findings
      indicate that priming of cord blood neutrophils appears to be induced by labour
      and can be dissociated from increased ALP activity.

PMID- 8750313
TI  - Antiperinuclear factor in the diagnosis of juvenile rheumatoid arthritis.
AB  - The antiperinuclear factor (APF) was estimated by immunofluorescent microscopy in
      the sera of 32 children and adolescents with juvenile rheumatoid arthritis (JRA)
      in comparison to a group of 16 children and adolescents with other rheumatologic
      disorders and a group of 20 age-matched healthy subjects. The APF was detected in
      17 children with JRA (53%), in only one patient in the group of other
      rheumatologic disorders (6%), and in 2 healthy children (10%). Accordingly, APF
      had a sensitivity of 53%, a specificity of 92%, and a diagnostic efficiency of
      74% in our series. APF was found to have a higher diagnostic gain in rheumatoid
      factor (RF) seronegative cases than did the RF in APF negative cases, meaning a
      higher sensitivity of APF as compared to the RF. The APF seropositivity was
      neither altered by the use of corticosteroids nor influenced by the age, gender,
      duration of illness, or number of joints affected. Three out of 5 patients with
      JRA had the APF detected in their synovial fluid; they were running rather a
      severe course of illness. The use of the APF could be an aid in the diagnosis of
      JRA.

PMID- 8750314
TI  - Comparison of cytokine production in blood cell cultures of healthy children and
      adults.
AB  - The production of the cytokines IL-1-alpha, IL-1-beta, IL-2, TNF-alpha, and INF
      gamma was measured by a sensitive immunological assay in stimulated whole blood
      cell cultures from 52 healthy children (33 aged from 1 to 9 years and 19 aged
      between 10 and 17 years) and 67 healthy adults. When the higher absolute
      mononuclear cell counts in the peripheral blood samples of the children were
      taken into account, the relative production of all measured cytokines was lower
      in the cell cultures of the children than of the adults. In the group of the
      younger children (< 10 years) the differences were significant for all measured
      cytokines. In the group of older children (> or = 10 years) the values were
      higher than in the younger children but lower than in adults. The findings
      indicate that the cellular immunological competence is or can be reduced in
      children and adolescents, particularly young children below 10 years of age.
      There seems to be a gradual development of cytokine production during childhood.

PMID- 8750315
TI  - Cryptococcal meningitis in a child with hyperimmunoglobulin E syndrome.
AB  - A 13-year-old boy with hyperimmunoglobulin E (hyper-IgE) syndrome presented with
      headache, blurred vision, photophobia and bilateral papilledema due to
      cryptococcal meningitis. Treatment with amphotericin B, and S-fluorocytosine for
      several weeks and repeated lumbar punctures did not reduce the intracranial
      pressure, and a myeloperitoneal shunt was performed. The child was maintained on
      fluconazole for an additional six months. Patients with hyper-IgE syndrome are at
      increased risk of opportunistic fungal infections such as cryptococcal
      meningitis.

PMID- 8750316
TI  - Anatomy of the medial temporal lobe.
AB  - The medial temporal lobe concept is an example of neurojargon rich in clinical
      and behavioral meaning, but sparse in neuroanatomical meaning except for
      topography. Like the concept of anterior speech area, many know roughly where it
      is located and what its functional correlates are, but not a lot else. At least
      three anatomical entities qualify as components of the medial temporal lobe.
      These include the amygdaloid body, the hippocampal formation, and the
      parahippocampal cortices that cover them superficially and are visible on the
      external surface of the hemisphere. For the greater part of this century,
      topographical observations, dissection, and descriptive data from passive
      staining methods have formed the principal source of information about the
      anatomy of the medial temporal lobe. However, in the past two decades much new
      information has emerged from experimental neuroanatomical studies in nonhuman
      primates and from neuropathological studies in humans. With magnetic resonance
      imaging (MRI), previous neuroanatomical detail, which earlier may have seemed
      like descriptive minutia, has now come alive and assumed substantial relevance in
      neurological and psychiatric diagnosis. Some of the emerging concepts as they
      relate to the neuroanatomy of the primate brain are highlighted and summarized
      here.

PMID- 8750317
TI  - MRI-based hippocampal volumetrics: data acquisition, normal ranges, and optimal
      protocol.
AB  - The process of producing magnetic resonance (MR) volume measurements can be
      divided into considerations of acquisition and postprocessing of the MR data.
      With careful attention to both of these, precise and reproducible measurements
      can be achieved. A statistical description of hippocampal measurements in normal
      volunteers must be available for comparison if volumetrics are employed either
      for clinical or research purposes. A wide range in "normal" hippocampal volume is
      present in the studies of normal young adults that have been reported to date.
      This variability is most probably due to interinstitutional differences in
      hippocampal boundary criteria, and in the software employed for counting pixels
      in a defined region of interest (ROI). Because the numeric output from the volume
      measurement procedure is highly technique-dependent, the statistical description
      of "normal" should be determined or calibrated at each institution wishing to use
      these techniques.

PMID- 8750318
TI  - Hippocampal MRI volumetrics and temporal lobe substrates in medial temporal lobe
      epilepsy.
AB  - Forty-nine consecutive patients undergoing anteromedial temporal lobe resection
      for medically intractable temporal lobe seizures, and averaging 2 yr (range 6 mo
      to 4 yr) postoperative follow-up, were selected for a retrospective study. This
      study correlated magnetic resonance imaging (MRI) derived hippocampal
      volumetrics, preoperative demographics, postoperative seizure control, and tissue
      analysis, including hippocampal CA (cornu ammonis) field neuronal, and glial cell
      counts, and immunohistochemistry (IHC) evidence for dentate sprouting and
      reorganization. These measures were compared in hippocampi with or without an
      adjacent presumptive epileptogenic temporal lobe mass. Mesial temporal sclerosis
      (MTS) was defined as > 50% neuronal cell loss averaged across all CA fields with
      NPY (neuropeptide-y) and somatostatin reorganization. These patients may or may
      not include granule cell sprouting as determined by dynorphin staining. Patients
      were divided into two groups based on CA field neuronal cell counts, one
      averaging > 50% cell loss and one averaging < 50% cell loss. For the MTS group (N
      = 38), 89% had significant volumetric atrophy of the ipsilateral hippocampus, 74%
      had dentate reorganization, and complete seizure control was seen in 76% of these
      patients. In one subgroup of the < 50% cell loss group, patients with medial
      temporal lobe epilepsy caused by a mass in the medial temporal lobe (mass group)
      (N = 6), 33% demonstrated significant volumetric atrophy of the hippocampus
      ipsilateral to the mass, 0% had dentate sprouting, and seizures were completely
      controlled in 67%. For the second subgroup of the < 50% cell loss group, patients
      without mass lesions (N = 5) who were classified as the paradoxical medial
      temporal lobe epilepsy group (paradoxical group), 20% had ipsilateral hippocampal
      atrophy, 0% had dentate reorganization, and complete seizure control was seen in
      60% of these patients. In conclusion, for the MTS group, hippocampal atrophy
      proven by MRI volumetrics was highly predictive of significant neuronal cell loss
      and an excellent indicator of success. However, in patients who had a foreign
      mass, hippocampal atrophy was not necessarily indicative of significant neuronal
      cell loss and MRI volumetrics was not a factor in the determination of a
      successful outcome. Furthermore, patients without mass lesions who have normal
      volumetrics but demonstrate hippocampal disease through invasive electrode
      monitoring, are likely to have paradoxical medial temporal lobe epilepsy,
      seizures beginning at a later age, and a lower, but not insignificant, success
      rate than the classical mesial temporal sclerosis group.

PMID- 8750319
TI  - Morphometry in temporal lobe epilepsy.
AB  - We demonstrate a method for quantitating changes in volume and morphology of the
      temporal lobe in epilepsy. The temporal lobes of 10 neurologically normal
      subjects and six subjects with well defined left-sided mesial temporal epilepsy
      were studied. From high resolution T1-weighted magnetic resonance images, the
      grey and white matter were manually segmented over a predetermined extent. The
      volumes of the grey and white matter were determined. Using the segmented images,
      the grey matter/CSF surface and the white matter/grey matter surface were
      reconstructed, allowing estimates of the surface area and calculation of indices
      of curvature for the two surfaces. The index of curvature was calculated for each
      vertex of a polygonal mesh that was fitted to the surfaces. An index of grey
      matter thickness (grey matter volume/white matter surface area) was also
      calculated. There was a significant bilateral decrease in the total volume (p <
      .01), grey matter volume (p < .001) and grey matter thickness index (p < .05) in
      epileptic subjects. In addition, there was a bilateral decrease in white matter
      surface area (p < .05) and a small left-sided decrease in white matter volume (p
      < .05) in epileptic subjects. The average distributions of indices of curvature
      for both surfaces differed significantly (p < .05) between normal and epileptic
      subjects. In the grey matter/CSF surface of normal subjects, a large peak
      corresponding to surface concavity was present. The amplitude of this peak was
      significantly lower in epileptic subjects (p < .05 for the right hemisphere; p <
      .001) for the left hemisphere).

PMID- 8750320
TI  - The diagnosis of hippocampal sclerosis: other techniques.
AB  - Pathologically, hippocampal sclerosis (HS) is characterized by neuronal loss and
      gliosis affecting particularly the pyramidal neurons of CA1, CA3, and CA4 with
      relative sparing of the CA2 neurons. This can be identified in vivo with magnetic
      resonance (MR) imaging techniques that can reveal both morphological and signal
      abnormalities. The morphological changes are atrophy and loss of the normal
      internal architecture of the hippocampus as seen in coronal section. There is
      also T1- and T2-weighted signal abnormality in the hippocampus. Quantitative
      techniques are very good at measuring any single one of these features, but the
      spectrum of HS includes cases in which a single feature can occasionally be
      misleading. Also, quantitation focuses entirely on the hippocampus, and it is
      becoming clear that HS may exist in the presence of other brain pathology that
      may affect proper management of the patient. Therefore, quantitative measures
      should always be interpreted in the context of optimised imaging sequences and
      visual inspection. For routine clinical purposes, the relative reliance on
      quantitation (hippocampal volume or T2 measurements) depends entirely on the
      yield of visual inspection in any institution. This, in turn, depends on whether
      optimised imaging is performed and on the familiarity of the reporting specialist
      with the MRI features of HS. A technique which approaches 95-100% compared with
      pathology is essential in any epilepsy centre, and optimised visual analysis can
      achieve this. There are some cases where quantitation of a single feature can be
      misleading, so visual analysis should always be performed, and complements any
      quantitative study.

PMID- 8750321
TI  - New technical developments in magnetic resonance imaging of epilepsy.
AB  - Within the last several years a number of technical developments have been made
      in magnetic resonance imaging (MRI) that can potentially impact clinical and
      research MR imaging application in epilepsy. These include developments in
      instrumentation and in pulse sequences. Advances in instrumentation include
      higher capacity gradient systems and multiple receiver coils as directed to brain
      imaging. Advances in pulse sequence include use of fast or turbo-spin-echo
      techniques, variants of echo-planar imaging, and sequences such as fluid
      attenuation inversion recovery (FLAIR) targeted to specific applications of brain
      imaging. The purpose of this paper is to review several of these developments.

PMID- 8750322
TI  - Novel MR image contrast mechanisms in epilepsy.
AB  - A range of magnetic resonance (MR) parameters are introduced, which can give rise
      to image contrast by using suitable pulse sequences, and that can be measured
      quantitatively. Their relationship to tissue pathology is given as far as
      possible. Techniques for their measurement, and results from multiple sclerosis,
      stroke, and epilepsy are given. The parameters are proton density, T1, T2,
      transverse magnetisation decay, which gives estimates of extracellular water and
      myelin concentrations, magnetisation transfer ratio and T1sat, and diffusion
      (including trace and anisotropy measured from the tensor matrix).

PMID- 8750323
TI  - Curvilinear reconstruction of 3D magnetic resonance imaging in patients with
      partial epilepsy: a pilot study.
AB  - In an attempt to better delineate the abnormalities associated with focal
      cortical dysgenesis, we performed curvilinear reformatting of the cortex from 3D
      magnetic resonance (MR) images. Illustrative patients with partial seizures and
      conventional orthogonal MRI evaluation show that small regions of cortical
      thickening suggestive of focal dysplastic lesions may not be recognized. In three
      such patients the curvilinear reformatting demonstrated two additional focal
      abnormalities of the cortical gyri and better defined the two focal lesions found
      on conventional orthogonal MR images. This method promises to be a useful tool in
      the evaluation of epileptic patients with proven or suspected subtle structure
      cortical abnormalities, particularly focal neuronal migration disorders where
      cortical thickening, abnormal gyral pattern, and poor delineation of the gray
      white matter transition are the main findings.

PMID- 8750324
TI  - Clinical correlations: MRI and EEG.
AB  - Main structural correlates of epileptogenesis include hippocampal sclerosis,
      cortical dysgenesis, foreign tissue lesions, gliosis, and dual pathology (a
      combination of any two). These structural abnormalities are now increasingly
      defined with MRI, enabling systematic EEG correlative analyses. Hippocampal
      atrophy (HA) and increased T2 signal in medial temporal structures predict the
      presence of mesial temporal sclerosis with a high degree of sensitivity and
      specificity. In 50 patients with clinical evidence of temporal lobe epilepsy and
      isolated HA, ictal scalp EEG was concordant to the atrophic temporal lobe in 33,
      nonlateralizing in 12, obscured in 3, and bilateral in 2, but it was discordant
      in none. Earlier reports of higher levels of discordance may be ascribed to the
      presence of dual pathology or to differing MRI and EEG criteria for localization.
      In a more inclusive group of 101 patients with unilateral HA, ictal scalp EEG was
      obtained in 99. It was unlocalized in 53, localized elsewhere in 9, and localized
      to the atrophic temporal lobe in 38. Of those, 51 patients had intracranial EEG:
      12 were unlocalized, 29 were localized to the atrophic hippocampus, and 9 were
      localized elsewhere. There is thus a rare but definite subgroup of patients with
      unilateral HA who have EEG localization elsewhere than the atrophy. The
      successful cure of seizures in half these patients after removal of the EEG focus
      confirms the importance of this observation and emphasizes the search for more
      dual pathology that has remained undetected on MRI. About 10% of the patients
      with HA have significant atrophy bilaterally, and several series have confirmed
      that surgical success is predicted by removal of the EEG identified seizure onset
      area, not the more or less atrophic hippocampus. In patients with other kinds of
      dual pathology, including HA and foreign tissue lesions or cortical dysgenesis,
      EEG is also paramount in predicting the site of epileptogenesis for surgical
      intervention. EEG correlates of cortical dysgenesis are heterogeneous, but EEG
      has potential to provide accurate localization of the site of epileptogenesis in
      foreign tissue lesions also. In a study of 59 lesional patients, a small number
      of patients with low grade astrocytomas and oligodendrogliomas consistently
      localized by EEG to an area elsewhere than the lesion, and failed seizure control
      when the lesion was removed. Although MRI can demonstrate the structural
      correlate of the epilepsy in many situations, rare patients, particularly with
      certain tumors, cortical dysgenesis, and dual pathology, require EEG for accurate
      localization.

PMID- 8750325
TI  - Clinical applications: MRI, SPECT, and PET.
AB  - MRI, PET, and SPECT are all used to image abnormalities in the epileptic brain.
      Comparison of the techniques is difficult because they measure different aspects
      of the epileptic process--structure, metabolism, and perfusion. SPECT is the only
      one that can be systematically applied during seizures, while all three are used
      to image interictal abnormalities. Literature review suggests that of interictal
      techniques, PET has the highest diagnostic sensitivity in temporal lobe epilepsy
      (TLE) (84% vs. 66% for SPECT, 55% for qualitative MRI, 71% for quantitative MRI)
      while SPECT has the highest sensitivity in extratemporal epilepsy (ETE) (60% vs.
      43% for MRI and 33% for PET). The highest diagnostic sensitivity and specificity
      were achieved by ictal imaging with SPECT (90% in TLE, 81% in ETE). The
      techniques, however, were not always redundant. One reason for the wide
      discrepancy of results in TLE and ETE might be the differing pathologic
      substrates. A literature review of imaging findings associated with mesial
      temporal sclerosis (MTS), developmental lesion or tumor as the underlying
      abnormality associated with epilepsy supports this explanation. PET and MRI are
      much more sensitive to MTS than SPECT (100%, 95% vs. 70%). On the other hand, in
      developmental lesions the three techniques are equally sensitive (88-92%) and in
      tumors, MRI was most sensitive (96%) and SPECT least (82%). A study at NIH
      explains the differing sensitivities: using PET to measure both blood flow and
      metabolism revealed discrepant findings in the same patients. Preliminary
      evidence also indicates that the distribution of hyperperfusion on ictal SPECT
      can differentiate subtypes of TLE. Combining the results of refined imaging
      techniques holds great promise in epilepsy localization and diagnosis.

PMID- 8750326
TI  - MRI hippocampal volume and neuropsychology in epilepsy surgery.
AB  - A review is provided of recent findings on relationships between neurocognitive
      test data and magnetic resonance imaging (MRI)-determined hippocampal volumes in
      nonlesional temporal lobectomy patients. The difference between the right and
      left hippocampal volumes is correlated with postoperative verbal memory in left
      temporal lobectomy patients who do not have lesional pathology. MRI hippocampal
      volume data are not associated with measures of executive functioning or naming.
      Sex differences have been found for verbal memory outcome as women have better
      verbal memory following left temporal lobectomy. Sex differences have also been
      found in the relationships between verbal and visual memory, and hippocampal
      volume data. The systematic combination of MRI-acquired morphological data and
      neuropsychological test data may further our understanding of neurocognitive
      function, and provide clinically useful data for counseling epilepsy surgery
      patients. The current data are promising with regard to prediction of memory
      outcome following temporal lobectomy, but they do not yet allow for prediction of
      specific individual patient outcomes. Rather, the currently available data
      support counseling patients based on the memory outcome of others with similar
      characteristics.

PMID- 8750327
TI  - Clinical correlations with hippocampal atrophy.
AB  - There is now a consensus that magnetic resonance imaging (MRI) is a sensitive and
      specific indicator of mesial temporal sclerosis (MTS) in patients with partial
      epilepsy. MTS is the most common pathological finding underlying the
      epileptogenic zone in patients undergoing temporal lobe surgery for medically
      refractory partial seizures. MRI-based hippocampal volumetric studies (i.e.,
      quantitative MRI), has been shown to provide objective evidence for hippocampal
      atrophy in patients with MTS. The hippocampal volume in the epileptic temporal
      lobe has correlated with the neuronal cell densities in selected hippocampal
      subfields. A history of febrile seizures in childhood and age of unprovoked
      seizure onset have been associated with MRI-based hippocampal volumetry. There is
      conflicting evidence regarding the relationship between the duration of the
      seizure disorder and volumetry. Quantitative MRI has compared favorably to other
      noninvasive techniques (e.g., scalp-recorded EEG), in indicating the diagnosis of
      medical temporal lobe epilepsy (MTLE). MRI-identified hippocampal atrophy has
      also been a favorable prognostic indicator of seizure outcome after temporal lobe
      surgery. The presence of hippocampal atrophy appears to serve an in vivo
      surrogate for the presence of MTS.

PMID- 8750328
TI  - MRI in cerebral developmental malformations and epilepsy.
AB  - Cerebral developmental malformations are increasingly recognized as a major cause
      of developmental delay and epilepsy. The incidence of these developmental
      malformations in patients with epilepsy is not known, but epilepsy surgery data
      suggest that this pathology is commonly seen in children who undergo epilepsy
      surgery for intractable epilepsy. These malformations can be diagnosed by a
      combination of clinical, neurophysiological, and imaging techniques. However,
      imaging techniques such as MRI have been able to provide in vivo recognition of
      many of these malformations and have contributed to the recognition of specific
      syndromes. These malformations can be classified on an anatomical basis either
      into diffuse, unilateral, or generalized. However, a combination of imaging data
      in conjunction with genetics and embryology may be more appropriate in the
      future. Further technical developments promise to increase the sensitivity of MRI
      in detecting these malformations and may help to delineate the possible biology
      of these disorders.

PMID- 8750329
TI  - Increasing the yield from volumetric MRI in patients with epilepsy.
AB  - Volumetric magnetic resonance imaging has become a routine investigation in the
      management of patients with chronic partial epilepsy. However, even with the use
      of reformatted images, an underlying cause for epilepsy cannot be found in many
      of these patients. We show that further processing of the data, including three
      dimensional reconstruction and quantitative analysis of the volume and complexity
      of the images in three dimensions, reveals additional positive information in up
      to 75% of patients. This may be useful for surgical planning, prognostication,
      and understanding of the structure and development of the human brain.

PMID- 8750330
TI  - MR characteristics of neoplasms and vascular malformations associated with
      epilepsy.
AB  - We assessed the magnetic resonance (MR) imaging characteristics of two categories
      of epileptogenic substrates, neoplasms, and vascular malformations, to determine
      MR sensitivity and typical imaging features. A blinded retrospective analysis was
      performed on MR scans from 41 patients who had a neoplasm or vascular
      malformation surgically resected as treatment for medically refractory epilepsy.
      Abnormalities were assessed for sensitivity of MR detection, prediction of
      pathologic category, location, calvarial remodelling, signal intensity, and
      effect on adjacent tissue. Pathologic findings consisted of 33 tumors and 8
      vascular malformations. We correctly localized 100% of the 41 lesions and
      predicted the correct pathologic category for 95% of these lesions. Neoplastic
      and vascular lesions (NVLs) associated with epilepsy had certain characteristic
      features. The temporal lobe was the most common site for NVL, involved in 68%.
      NVL were located in the brain periphery in 85% and remodelled the calvarium in
      32%. NVL were associated with mass effect in 61%, volume loss in 1%, and no
      effect on adjacent tissue in 37%. NVL associated with epilepsy can be detected
      with high sensitivity using MR imaging. The temporal lobe location, cortical
      involvement, and calvarial remodelling are findings typical of NVL. MR
      characteristics can successfully predict the pathologic substrate of these
      lesions.

PMID- 8750331
TI  - Magnetic resonance imaging and epilepsy: neurosurgical decision making.
AB  - Advances in magnetic resonance imaging (MRI) techniques have had an important
      impact on the decision-making process leading to surgical resection for chronic
      seizures. The MRI is now obtained relatively early in the work-up, and, when it
      shows abnormality, it assumes a crucial role in the detection of specific
      surgically remediable syndromes. These syndromes, when diagnosed by MR and other
      confirmatory studies such as electroencephalography (EEG), positron emission
      tomography (PET), magnetoencephalography (MEG), and neuropsychological testing,
      define the essential part of the surgical plan; that is, removal of the disease
      substrate. The availability of a host of MR techniques enable us to investigate
      epilepsy not only as a structural pathology but as physiological pathology
      reflected in abnormal blood flow, metabolism, and synaptic transmission. The
      mainstay of surgical treatment is the removal of the anatomic pathology, but
      other MR techniques may be helpful in the delineation of dual pathology in
      lesional cases, in appreciation of the full extent of microscopic pathology in
      developmental lesions, and in the imposition of restrictions on the resection
      based upon functional mapping. Finally, functional and anatomic maps obtained
      preoperatively can be related directly to the spatial coordinates of the exposed
      brain in the operating room using MRI-based frameless stereotactic methods. The
      final outcome, then, is the removal of the disease substrate without injury to
      adjacent, functionally salient cortical regions.

PMID- 8750332
TI  - Overview--the role of NMR spectroscopy in epilepsy.
AB  - Nuclear magnetic resonance (NMR) spectroscopy permits noninvasive, serial
      measurements of several metabolites with important neurobiologic roles in
      localized brain regions in vivo. Over the last decade, this technique has been
      applied to investigations of both animals and humans with epilepsy. Several
      nuclei that include specific proton, phosphorus, and carbon isotopes provide NMR
      signals that measure specific compounds in vivo. This paper reviews the studies
      that have used these multinuclear NMR techniques to investigate the role of these
      methods in the diagnosis and pathogenesis of epilepsy.

PMID- 8750333
TI  - Application of high field spectroscopic imaging in the evaluation of temporal
      lobe epilepsy.
AB  - Previous spectroscopic imaging studies of temporal lobe epilepsy have used
      comparisons of metabolite content or ratios to lateralize the seizure focus.
      Although highly successful, these studies have shown significant variations
      within each of the groups of healthy subjects and patients. This variation may
      arise from the natural differences seen in metabolite concentration in gray and
      white matter, the complex anatomy seen about the hippocampus, and the large
      voxels typically employed at 1.5 T. Using a 4.1 T whole body system, we have
      acquired spectroscopic images with 0.5 cc nominal voxels (1 cc after filtering)
      to evaluate the regional variation in metabolite content of the hippocampus,
      temporal gray and white matter, midbrain, and cerebellar vermis. Using a
      threshold value of 0.90 for CR/NAA, a value 90% of all normal hippocampal voxels
      lay below, we have correctly identified the presence of epileptogenic tissue in
      patients with unilateral as well as bilateral seizures. By using comparisons to
      healthy values of the CR/NAA ratio, this method enables the visualization of
      bilateral disease and provides information on the extent of gray matter
      involvement.

PMID- 8750334
TI  - Application of spectroscopic imaging in epilepsy.
AB  - Functional and anatomical neuroimaging has had a dramatic effect on the
      evaluation of patients for seizure surgery. The demonstration by PET that the
      epileptogenic focus has interictal metabolic abnormalities has allowed a greater
      number of patients to come to seizure surgery, with fewer of these patients
      requiring intracranial electrode evaluations. Metabolic changes have also been
      demonstrated utilizing single voxel and whole brain 1H and 31P MRS imaging
      techniques with the interictal focus characterized by increased Pi, pH, and
      decreased PME and NAA. These findings can be used to accurately lateralize
      temporal lobe as well as frontal lobe epilepsy. Furthermore, there is evidence
      that these findings can be used to localize the seizure focus with the changes
      specific for the epileptogenic region; although, more diffuse changes both
      ipsilaterally and contralaterally have been seen. In patients with anterior
      hippocampal seizure foci the pH is significantly alkaline only in the ipsilateral
      hippocampus, whereas the increased Pi and decreased PME can be seen throughout
      the ipsilateral temporal lobe. When compared to controls the contralateral
      hemisphere is acidotic. Decreased NAA concentrations as well as NAA/Cr ratios
      have been demonstrated in the epileptogenic region in temporal and frontal lobe
      epilepsy. The decreased NAA has been correlated with the severity of cell loss,
      and may be a more sensitive measure than qualitative or quantitative measures of
      the hippocampal atrophy; however, the NAA decrease is more widespread than just
      the epileptogenic focus but may be maximal at the site of seizure initiation. In
      preliminary work, NAA maps of deviation from normality have suggested that the
      maximal change to coincide with the epileptogenic region. These results suggest
      that in focal epilepsy there is abnormal metabolic activity throughout the brain
      detectable by MRS, with patterns of metabolic asymmetry that are useful for
      seizure localization.

PMID- 8750335
TI  - Proton magnetic resonance spectroscopic images and MRI volumetric studies for
      lateralization of temporal lobe epilepsy.
AB  - We obtained 2D magnetic resonance (MR) spectroscopic images (MRSI) and MRI
      volumetric measurements (MRIV) of amygdala and hippocampus in 30 consecutive
      patients with temporal lobe epilepsy (TLE) being evaluated for surgical
      treatment. Both MRSI and MRIV lateralization showed good agreement with the
      current gold standard of clinical-EEG lateralization. Each exam separately
      correctly lateralized 25 out of 30 patients with no false lateralization.
      Combining both exams, lateralization could be achieved in 28 out of 30 patients.
      The two patients with no significant asymmetry had bitemporal EEG abnormalities,
      and bilateral damage on both MRIV and MRSI. There was a good correlation between
      the magnitude of the MRSI and MRIV asymmetry (Pearson coefficient = 0.83; p <
      .0001). Both MRSI and MRIV were normal in our patients with seizures originating
      outside the temporal lobes. Both MRIV and MRSI can lateralize TLE in 83% of
      patients. Combination of the two modalities allows lateralization in 93% of
      patients. Patients who cannot be lateralized generally have symmetrical
      bitemporal abnormalities; they are not incorrectly lateralized. The structural
      and chemical pathologic abnormalities seen in TLE seem to be associated with the
      seizure focus, and may be as, or even more, reliable than a few recorded seizures
      in predicting the side from which most seizures originate.

PMID- 8750336
TI  - N-acetylaspartate and epilepsy.
AB  - Proton magnetic resonance spectra include signals from N-acetylaspartate,
      creatine + phosphocreatine, and choline-containing compounds. Abnormalities in
      these signals can be used in the assessment of patients with intractable
      epilepsy. In particular, they provide a means of identifying metabolic
      abnormalities within the temporal lobes, detecting bilateral and diffuse
      pathology, and aiding lateralization of the seizure focus. The pathology
      demonstrated on MRS can also be related to cognitive dysfunction.

PMID- 8750337
TI  - Symbiosis between in vivo and in vitro NMR spectroscopy: the creatine, N
      acetylaspartate, glutamate, and GABA content of the epileptic human brain.
AB  - High resolution 1H NMR spectroscopy was used to analyze temporal lobe biopsies
      obtained from patients with epilepsy. Heat-stabilized cerebrum, dialyzed
      cytosolic macromolecules, and perchloric acid extracts were studied using one-
      and two-dimensional spectroscopy. Anterior temporal lobe neocortex was enriched
      in GABA, glutamate, alanine, N-acetylaspartate, and creatine. Subjacent white
      matter was enriched in aspartate, glutamine, and inositol. The N
      acetylaspartate/creatine mole ratio was lower in anterior temporal neocortex with
      mesial (0.66) than neocortical (0.80) temporal lobe epilepsy. Human brain biopsy
      samples were separated into crude and refined synaptosomes, neuronal cell bodies,
      and glia using density gradient centrifugation. Neuronal fractions were enriched
      in glutamate and N-acetylaspartate. Glial cell fractions were enriched in
      lactate, glutamine, and inositol. The creatine content was the same in biopsied
      epileptic cortex (8.8-8.9 mmol/kg) and normal in vivo occipital lobe (8.9
      mmol/kg). Glutamate content was higher in epileptic cortex at biopsy (10.1-10.5
      mmol/kg) than normal in vivo occipital lobe (8.8 mmol/kg). GABA content was
      higher in biopsies of epileptic cortex (2.3-2.2 mmol/kg) than in normal in vivo
      occipital lobe (1.2 mmol/kg). N-acetylaspartate content was lower in biopsied
      epileptic temporal cortex (5.8-6.8 mmol/kg) than normal in vivo occipital lobe
      (8.9 mmol/kg). Paired in vivo and ex vivo measurements are critical for a firm
      understanding of the changes seen in the 1H-spectra from patients with epilepsy.

PMID- 8750338
TI  - NMR studies of brain 13C-glucose uptake and metabolism: present status.
AB  - One of the common features of epilepsy is a change in glucose metabolism at the
      site of seizure activity during and between seizures. The noninvasive in situ
      study of glucose transport and metabolism by NMR can potentially provide detailed
      information about this phenomena. In this short review, we will discuss the
      principles of 13C-glucose NMR studies of the brain and compare the advantages and
      disadvantages of this method to those of 18F-deoxyglucose studies using positron
      emission tomography (PET).

PMID- 8750339
TI  - High-field MRS studies in brain slices.
AB  - We are applying multi-nuclear high-field (500 MHz) MR spectroscopy of
      metabolising whole tissue preparations of the mammalian brain to studies on
      individual components of convulsions, which include prolonged depolarization,
      metabolic deprivation, and the effects of excitotoxins. The responses of glial
      cells and neurones can be partially distinguished by following labelling patterns
      of metabolic intermediates from 13C-labelled glucose or acetate (which enters
      only glial cells). This approach clearly confirmed our earlier indications that
      the metabolic response to depolarization (40 mM extracellular K+) occurs
      essentially in glial cells. Some evidence for metabolic shuttling between glia
      and neurones was obtained from the changes in C3/C4 ratios of glutamate and
      glutamine, and the C2/C3 of GABA. Mechanisms for metabolic support of neurones by
      glia may be of importance in neuronal protection under such metabolic stress as
      occurs in epilepsy. Changes in free intracellular divalent cations ([Ca2+]i and
      [Zn2+]i) were monitored using the 19F-MRS indicator, 5FBAPTA. Large increases in
      [Ca2+]i and decreases in PCr were produced by excitotoxins (glutamate and NMDA),
      depolarization or ischemia, but intracellular Zn2+ appeared only after exposure
      to the excitotoxins. The NMDA receptor blocker, MK801, removed all of the
      responses to NMDA, but only prevented the appearance of Zn2+ observed with
      glutamate. These results indicate that the damage caused to neurones by such
      insults as convulsions is not due simply to the presence of excessive excitotoxic
      glutamate.

PMID- 8750340
TI  - Diffusion-weighted imaging in epilepsy.
AB  - Diffusion-weighted imaging (DWI) is a relatively new magnetic resonance imaging
      (MRI) technique that can be used to probe the microenvironment of water. Contrast
      in DWI depends on properties different from traditional T1 and T2 contrast, and
      is derived form the translational motion of water molecules. Since it is
      reasonable to think that a change in the microenvironment of water might be
      reflected in a change in water diffusion characteristics, the quantitative
      assessment of the (apparent) diffusion coefficient ADCw may represent a unique
      means of assessing tissue status. DWI has already shown great utility in the
      study of cerebral ischemia in animal models and has proved useful in the early
      identification of cerebral ischemia in patients. More recent reports have
      indicated a potential for DWI in studying epilepsy. Here, we briefly review some
      of what is known about the measurement of ADCw in ischemia and compare these
      results with what has recently been reported for epilepsy. In this manner we hope
      to better understand the underlying mechanisms behind changes in water diffusion
      associated with specific pathologies.

PMID- 8750341
TI  - Ictal imaging using functional magnetic resonance.
AB  - Magnetic resonance imaging (MRI) can now provide maps of human brain function
      with high spatial and temporal resolution. This noninvasive technique can also
      map the cortical activation that occurs during focal seizures, as demonstrated
      here by the results obtained using a conventional 1.5 T clinical MRI system for
      the investigation of a 4-year-old boy suffering from frequent partial motor
      seizures of his right side. FLASH images (TE = 60 ms) were acquired every 10 s
      over a period of 25 min, and activation images derived by subtracting baseline
      images from images obtained during clinical seizures. Functional MRI revealed
      sequential activation associated with specific gyri within the left hemisphere
      with each of five consecutive clinical seizures, and also during a period that
      was not associated with detectable clinical seizure. The activated regions
      included gyri that were structurally abnormal. These results demonstrate (a) that
      functional MRI can potentially provide new insights into the dynamic events that
      occur in the epileptic brain and their relationship to brain structure; and (b)
      that there is the possibility of obtaining similar information in the absence of
      clinical seizures, suggesting the potential for studies in patients were
      interictal electrical disturbances.

PMID- 8750342
TI  - The clinical neuroimmunotherapeutic role of melatonin in oncology.
AB  - In the past several years, interest in the immunophysiological role of the pineal
      gland and melatonin has grown to the extent that now their immunoregulatory role
      is widely recognized. Melatonin has immunoenhancing properties and it is able to
      counteract the immunodepression induced by acute stress, drug treatment (i.e.,
      anticancer drugs), and viral infections. Here we review the therapeutic efficacy
      of melatonin alone or in combination with interleukin-2 (IL-2) in cancer patients
      who did not respond to standard anticancer chemotherapies and/or refused any
      aggressive treatment. In this review, we summarize a series of reports from 1986
      through 1994 in which patients affected by metastatic solid tumors, metastatic
      non-small-cell lung cancer, advanced solid neoplasms, myelodysplastic syndrome,
      hepatocellular carcinoma, and advanced endocrine tumors were studied. The
      conclusion drawn from these studies is that melatonin protects against IL-2 and
      synergizes with the IL-2 anticancer action. This combined strategy represents a
      well tolerated intervention to control tumor growth. In most cases performance
      status and quality of life seem improved.

PMID- 8750343
TI  - Melatonin stimulates the activity of the detoxifying enzyme glutathione
      peroxidase in several tissues of chicks.
AB  - The pineal hormone melatonin has been shown to directly scavenge free radicals
      and to stimulate, in the mammalian brain, at least one enzyme, glutathione
      peroxidase, which reduces free radical generation. In the present studies, we
      examined the effect of melatonin on glutathione peroxidase activity in several
      tissues of an avian species. Melatonin (500 micrograms/kg), when injected into
      chicks, increased glutathione peroxidase activity within 90 min in every tissue
      examined. Tissue melatonin levels, measured by radioimmunoassay, also increased
      following its peripheral administration. Depending on the tissue, the measured
      increases in melatonin varied from 75% to 1,300% over the control values. The
      melatonin-induced increases in glutathione peroxidase activity varied with the
      tissue and were between 22% and 134%. These percentage increases in glutathione
      peroxidase activity were directly correlated with tissue melatonin content. These
      results suggest that melatonin induces the activity of the detoxifying enzyme,
      glutathione peroxidase, in several tissues in the chick. The findings also
      suggest that melatonin would reduce the generation of highly toxic hydroxyl
      radicals by metabolizing its precursor, hydrogen peroxide. Because of this
      ability to stimulate glutathione peroxidase activity, melatonin should be
      considered as a component of the antioxidative defense system in this avian
      species.

PMID- 8750344
TI  - Nocturnal plasma melatonin levels in patients suffering from chronic primary
      insomnia.
AB  - Polysomnographic sleep patterns and melatonin secretion were investigated in 10
      patients (age: 41.3 +/- 9.5 years) who suffered from chronic primary insomnia and
      complained predominantly about difficulties in maintaining sleep and in five
      healthy controls (age 27.2 +/- 0.7 years). Nocturnal plasma melatonin
      concentrations were obtained hourly, measured by direct radioimmunoassay and
      statistically compared between insomniacs and controls with age as a covariate.
      Plasma melatonin levels in the patient group tended to begin increasing earlier
      in the evening and were significantly (P < or = 0.01) lower during the middle of
      the night (peak value 82.5 +/- 26.5 pg/ml) than in the healthy controls (peak
      value 116.8 +/- 13.5 pg/ml). Among the patients, the most severely reduced
      nocturnal plasma melatonin levels were found in those patients with a history of
      sleep disturbance lasting for longer than five years (N = 6; age 41.8 +/- 11.7
      years; duration 15.3 +/- 5.9 years; peak value 72.1 +/- 25.0 pg/ml); whereas
      those chronic insomniacs affected for fewer than five years had relatively higher
      nocturnal levels (N = 4; age 40.6 +/- 6.5 years; duration 3.8 +/- 1.5 years; peak
      value 98.2 +/- 23.9 pg/ml). These results show that the circadian rhythm of
      melatonin secretion is disturbed in patients with chronic primary insomnia, and
      that the nocturnal plasma melatonin secretion is increasingly more affected the
      longer the patients are unable to maintain a regular sleep pattern.

PMID- 8750345
TI  - Permeability of pure lipid bilayers to melatonin.
AB  - Melatonin, the chief hormone of the pineal gland, has been reported to interact
      with a variety of different cells. This ubiquitously acting hormone has been
      found to interact with protein receptors both at the cell membrane and in the
      nucleus. Moreover, melatonin was recently shown to be a very potent hydroxyl
      radical scavenger. The present work focuses on the interaction of melatonin with
      pure lipid bilayers. It is shown that melatonin can cross multilamellar lipid
      vesicles, which are used here as model systems for the lipid phase of biological
      membranes. Thus, the data prove that melatonin can easily pass through the cell
      membrane and bath every part of the cell, as previously suggested in the
      literature. Melatonin lipid association constant was calculated based on the
      change of the hormone fluorescence intensity due to its penetration into the
      hydrophobic lipid phase. Though melatonin was recently shown to be highly soluble
      in aqueous media, its lipid association constant is rather high, indicating that
      the biological action of the hormone is likely to be at the membrane level,
      either via its interaction with membrane receptors, and/or as a lipoperoxidation
      radical scavenger.

PMID- 8750346
TI  - Inhibitory effects of melatonin on testosterone but not on androstenedione
      production during winter in the vespertilionid bat, Scotophilus heathi.
AB  - The possible effects of melatonin on testosterone and androstenedione production
      in vitro by testes of wild-caught bats, Scotophilus heathi, during different
      reproductive phases were investigated. Bats were captured during reproductive
      quiescent (April-August), recrudescent (September-October), breeding (November
      February), and winter dormancy (late December-January) phases. Testes were
      incubated in media-199 for 2 h at 37 degrees C with luteinizing hormone (LH) and
      with or without melatonin. Melatonin had no effect on LH-induced testosterone (T)
      or androstenedione (A) production during the quiescent, recrudescent, and
      breeding phases. However, it significantly (P < 0.05) suppressed LH-induced T
      production but had no effect on A during winter dormancy. Testicular 17 beta
      hydroxy steroid dehydrogenase (17 beta-HSD) activity was then measured in the
      testes from bats trapped during quiescence, breeding, and winter dormancy.
      Interestingly, melatonin along with LH caused suppression of 17 beta-HSD
      activities (3.56 +/- 0.03 unit/min/mg protein) when compared with levels of LH
      treated testes (7.10 +/- 1.15 unit/min/mg protein) during winter dormancy, while
      it had no significant effect on 17 beta-HSD activity during quiescence and
      breeding phases. These results suggest that in S. heathi, melatonin during winter
      dormancy suppresses LH-induced T production by the testes via the suppression of
      17 beta-HSD activity. This may be the reason for the decline in testicular
      activity during winter dormancy.

PMID- 8750347
TI  - Pharmacologic studies on the mechanism of melatonin-induced vasorelaxation in rat
      aorta.
AB  - The influence of several classes of drugs on the melatonin-induced vasorelaxation
      of isolated rat aorta were examined. Melatonin caused a dose-dependent relaxation
      of precontracted (30 mM KCl) aorta. This relaxant response was blocked by
      preincubating vessels with antagonists of vasoactive intestinal peptide.
      Substance P antagonists did not alter the response to melatonin. Pretreatment of
      vessels with 6-hydroxydopamine, lidocaine, or tetrodotoxin antagonized the
      relaxant response to melatonin. On the other hand, pretreatment with atropine +
      propranolol did not alter the response to melatonin. These experiments suggest
      that melatonin may exert part of its vasoactive actions by an interaction with
      perivascular nerve terminals.

PMID- 8750348
TI  - Daily variation in the content of indoleamines, catecholamines and related
      compounds in the pineal gland of Syrian hamsters kept under long and short
      photoperiods.
AB  - This study examined the diurnal changes in the content of 5-hydroxytryptophan (5
      HTP), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), N-acetylserotonin
      (NAS), melatonin, 5-methoxytryptophol (5-ML), noradrenaline (NA), dopamine (DA),
      and 3, 4-dihydroxyphenylacetic acid (DOPAC) in the pineal gland of Syrian
      hamsters kept under long (14L:10D) and short (10L:14D) photoperiods. The
      nocturnal increase in NAS and melatonin levels was dependent upon the prevailing
      photoperiod, with a prolonged duration when the night lengthened. In both
      photoperiods, NAS and melatonin contents increased several hours after the onset
      of darkness, and, in animals kept in short photoperiod, the levels of both
      compounds began to decrease before light onset. On the contrary, decreases were
      noted in 5-HT, 5-HIAA, and 5-ML contents during the night, which was directly
      proportional to the dark phase. 5-HTP levels did not show a rhythmic variation.
      Correlations between the mean values of 5-HT-related compounds showing daily
      rhythms were very high when group means were compared, but they decreased when
      values from individual animals were considered. In addition, when correlations
      were calculated on per-animal basis during the night phase, a weak negative
      correlation was found for 5-HT vs NAS and 5-HT vs melatonin, although the
      correlation of 5-HT with positively 5-HT-correlated compounds (5-HIAA and 5-ML)
      continued to be high. These results indicate that the nocturnal increase in the N
      acetyl transferase activity is the major factor generating the rhythm of pineal 5
      HT content, but that other photoperiod-dependent mechanisms (i.e., 5-HT synthesis
      or release) seem to be also implicated. On the other hand, this study shows that
      NA content in the Syrian hamster pineal gland does not exhibit daily variations,
      although marked nocturnal increases in the levels of DA and DOPAC were evident.
      These results suggest the existence of parallel daily alterations in pineal
      catecholamine synthesis and release, and suggest a role for DA in the pineal
      activation at night.

PMID- 8750349
TI  - Morphologic quantification of blood platelets by image analysis.
AB  - OBJECTIVE: For morphologic and functional investigations on the physiology and
      pathology of human blood platelets, their adhesion plays an important role. This
      feature is normally assessed concerning qualitative aspects, but there is a lack
      of quantitative investigations. STUDY DESIGN: We developed a model to quantify in
      vitro manipulations on thrombocytes by measuring their adhesion areas
      automatically. This was achieved by combining the VIDAS 2.5 image analysis system
      with reflection contrast microscopy (RCM). The evaluation was performed
      independent of the position of the grey value histogram by analyzing each
      digitized image corresponding to its individual mean grey value. RESULTS: The
      applicability and validity were verified from the example of a pharmacologic
      experiment administering the platelet stimulant oxidized low density lipoprotein
      (ox-LDL) to thrombocyte suspensions and confirming it by aggregometry. We
      assessed the temporal increase in adhesion area and mean total adhesion area of
      activated platelets, comparing unstimulated to stimulated ones. Ox-LDL
      accelerated the adhesion process and increased the adhesion area. CONCLUSION: The
      combination of RCM with consecutive image analysis provides useful parameters for
      in vitro examination on vital human platelets. Large amounts of data can be
      accumulated in a short time for an evaluation of influences of and on blood
      platelets.

PMID- 8750350
TI  - Quantitative image analysis of cell proliferation after balloon catheter injury
      in the rabbit carotid artery.
AB  - OBJECTIVE: To perform color image analysis to assess the course of morphometric
      and proliferative changes in the intima and media of rabbit carotid arteries
      following balloon injury. STUDY DESIGN: Proliferating smooth muscle cells were
      labeled with proliferating cell nuclear antigen and vizualized by
      immunohistochemical staining of histologic sections. Morphometry was performed on
      histologic cross-sections of injured arteries stained with hematoxylin. RESULTS:
      The development of intimal hyperplasia following an acute mechanical injury was
      detectable early on and was accompanied by a burst of cell proliferation. Medial
      cell proliferation peaked on day 3 after balloon injury, and the maximum of
      intimal cell proliferation was noted on day 7. CONCLUSION: The color image
      analysis method described here could be a useful tool in evaluating drugs for
      their ability to prevent restenosis.

PMID- 8750351
TI  - Small round cell tumors of bone and soft tissue. A morphometric and stereometric
      comparative analysis of 119 cases.
AB  - OBJECTIVE: To analyze the discriminative capability of morphometric assessment of
      nuclear morphology in the differential diagnosis of small round blue cell tumors
      (SRCTs) of bone and soft tissue. STUDY DESIGN: The study material consisted of
      glutaraldehyde-fixed, resin-embedded, semithin sections from 119 human tumors.
      Nuclear area, perimeter, maximum diameter, form factors and nuclear density were
      measured in at least 300 nuclei per case. RESULTS: Neuroblastoma (NB) (10 cases)
      showed the most regular pattern. Ewing's sarcoma (ES) (35 cases); atypical
      Ewing's sarcoma (AEs) (15 cases) and peripheral neuroectodermal tumors (PNET) (30
      cases) showed no significant differences regarding area, perimeter or form
      factors, but AEs showed a lower mean nuclear density that was statistically
      significant. Rhabdomyosarcomas (6 cases) and osteosarcomas (OS) (11 cases) were
      used as controls and showed several morphometric and stereometric differences
      with other SRCTs, whereas microcellular OSs (6 cases) shared features of SRCTs
      and conventional osteosarcomas. CONCLUSION: Morphometric characterization of
      nuclear features reveals differences between the distinct groups of SRCTs.
      Although overlapping occurred between all these groups at the individual case
      level, this study provides new support for the existence of morphologic links
      within the family of ES and PNET.

PMID- 8750352
TI  - Computer-assisted and visual methods of assessing cellular proliferation in
      tissue sections from non-Hodgkin's lymphoma a comparison.
AB  - OBJECTIVE: To compare computer-assisted and visual methods of assessing cellular
      proliferation using tissue sections from non-Hodgkin's lymphoma (NHL). STUDY
      DESIGN: The study group consisted of 20 specimens of NHL (10 indolent and 10
      aggressive). Three-micrometer serial sections were prepared and labeled for Ki-67
      (MIB1) and argyrophilic nucleolar organizer regions (AgNORs). Labeling was
      assessed by classic visual inspection and quantitative image analysis. RESULTS:
      Computer-assisted and visual Ki-67 labeling indices were significantly higher in
      aggressive than indolent NHL and were linearly related (r = .850, P < .0001).
      Although the visual and computer-assisted AgNOR counts were significantly higher
      in aggressive than indolent NHL, the correlation between these two counting
      methods was not significant (r = .407, P < .075). Linear regression analysis
      demonstrated a significant correlation between the Ki-67 visual labeling index
      and visual AgNOR count (r = .630, P < .003); however, no such relationship could
      be demonstrated between the remaining methods. CONCLUSION: The results of this
      study suggest that visual and computer-assisted methods of immunohistochemical
      and AgNOR analysis may not yield comparable results. This fact may be related to
      the method of analysis and the computer-assisted technique.

PMID- 8750353
TI  - Effects of radiotherapy on oral epithelium. Quantitative cytology using light and
      scanning electron microscopy.
AB  - OBJECTIVE: To determine the short- and long-term morphologic and morphometric
      effects of radiotherapy on exfoliated oral squames. STUDY DESIGN: Exfoliating
      squames were sampled from squamous carcinoma and contralateral clinically healthy
      sites from patients before and six weeks after radiotherapy and from patients who
      had received radiotherapy for oral squamous carcinoma five years previously.
      Morphologic and morphometric studies were undertaken using light and scanning
      electron microscopy (SEM). RESULTS: Six weeks after radiotherapy, nuclear area
      was significantly increased in cells from both healed tumor and contralateral
      sites. No differences were detected in cells from previous tumor and
      contralateral sites five years after radiotherapy. SEM revealed bizarre
      microplications in cells from malignant sites, and microplication widths were
      significantly increased. Occasional cells with atypical patterns were identified
      six weeks and five years after radiotherapy, but microplication dimensions were
      comparable to those of cells from contralateral clinically healthy sites.
      CONCLUSION: Radiotherapy produces a transient increase in nuclear area. Abnormal
      microplication patterns in cells from previous tumor sites five years after
      radiotherapy may reflect disordered maturation associated with radiation injury.

PMID- 8750354
TI  - Nuclear texture measurements in normal colorectal glands.
AB  - OBJECTIVE: To examine differences in epithelial cell nuclear texture along the
      length of normal, well-oriented colorectal glands. STUDY DESIGN: Histologically
      normal mucosa was obtained from four patients who had a family history of cancer
      and no hyperproliferation as assessed by bromodeoxyuridine immunohistochemistry.
      Serial sections were stained using the Feulgen technique and viewed to identify
      glands that were sectioned along their entire length. Two glands were sampled
      from each patient. Each gland was divided into three compartments based on
      epithelial cell counts along the length of the gland. Within each compartment, 10
      nuclei were randomly selected and their nuclear texture features measured using
      computerized image analysis. RESULTS: Analysis of variance demonstrated that
      significant differences exist in the nuclear texture of cells in the different
      compartments of the gland. Discriminant analysis selected three variables that
      were important and independent in the quantitative discrimination of the gland
      compartments. These features were related to the elliptical shape, optical
      density distribution and cooccurrence structure of the chromatin texture within
      the epithelial nuclei. CONCLUSION: It is clear that these differences are
      associated with the spatial variation in proliferation and differentiation status
      found within colorectal mucosal glands. Nuclear measurements from colorectal
      epithelium with near-normal architecture should therefore be stratified in
      relation to position within the gland. Nuclear texture and size measurements
      within defined compartments may provide a sensitive means of detecting early
      malignant transformation.

PMID- 8750355
TI  - DNA flow cytometry in node-positive breast cancer. Prognostic value and
      correlation with morphologic and clinical factors.
AB  - OBJECTIVE: To help clarify the possible usefulness of nuclear DNA content and S
      phase fraction (SPF) as additional prognostic factors in node-positive breast
      cancer patients because there is increased interest in the development of new
      factors that might provide more detailed prognostic information. STUDY DESIGN: We
      performed a DNA and SPF analysis by flow cytometry using a multivariate
      statistical model on a group of 139 node-positive breast cancer patients with
      clearly defined inclusion and exclusion criteria. RESULTS: The percentage of
      aneuploidy increased with the number of involved nodes. Aneuploid tumors were
      more often found among grade 3 and among receptor-negative tumors. Univariate
      analysis showed a strong effect on recurrence-free survival (RFS) for the number
      of involved nodes (P < .001) and for tumor size (P = .013). Grade 3 and receptor
      negative tumors showed a nonsignificant trend toward increased risk. The relative
      risk of aneuploid tumors was 1.19 (95% confidence interval, 0.75-1.87).
      Multivariate analysis revealed only the number of involved nodes to be an
      independent prognostic factor (P = .002); ploidy showed no effect (P = .684). SPF
      did not show any significant effect on RFS, even in a univariate analysis.
      CONCLUSION: These results suggest that nuclear DNA content and SPF correlate with
      morphologic factors. Their routine clinical use, however, in node-positive breast
      cancer patients receiving adjuvant therapy seems to have no clinical relevance
      and therefore can be omitted.

PMID- 8750356
TI  - P300 amplitudes vary inversely with continuum of risk in first degree male
      relatives of alcoholics.
AB  - First degree relatives of alcoholics show significantly reduced P300 amplitudes.
      This phenomenon is though to be a vulnerability marker of alcoholism. Relatives
      of alcoholics with higher family loading and early onset alcoholism are at
      greater risk for developing alcoholism. The high risk population may comprise
      subtypes differentiated by family history and/or age at onset of alcoholism, with
      differing risks, measurable in terms of the expression of the vulnerability
      marker. Four groups of alcohol-naive sons/male siblings of alcoholics (n = 64)
      were studied. The groups were constructed on the permutation of two defining
      characteristics: high family loading (two or more first degree alcoholic
      relatives) and early onset alcohol dependence (before 25 years) in the relatives.
      Comparison of P300 amplitude in an auditory paradigm showed significant inter
      group differences as well as progressive increase/normalization of amplitudes
      from the high loading-early onset group (HR1) to the low loading-late onset group
      (HR4), with the latter being indistinguishable from a separate group of (control)
      normals. There were no significant differences of P300 latency among the groups.
      We conclude that P300 amplitudes vary inversely with the presumed continuum of
      risk in those at high risk for developing alcoholism.

PMID- 8750357
TI  - Screening for CGG trinucleotide repeat expansion in the fragile X mental
      retardation 1 gene in schizophrenic patients.
AB  - Patients diagnosed using DSM-III-R criteria as having schizophrenia and other
      related disorders (n = 128) were assessed for CGG trinucleotide repeat expansion
      in the fragile X mental retardation 1 (FMR-1) gene. One subject, a woman with
      schizophreniform disorder, was found to have a premutation of the gene. Her case
      report is given. The present investigation supports the view that mutation or
      premutation of the FMR-1 gene is not of importance for the aetiology of the vast
      majority of schizophrenic patients.

PMID- 8750358
TI  - No evidence of linkage between manic depressive illness and the dopa
      decarboxylase gene or nearby region on chromosome 7p.
AB  - Dopa decarboxylase (DDC) is involved directly in the synthesis of dopamine and
      serotonin and indirectly in the synthesis of noradrenaline. The present study
      investigated two Danish families for linkage between manic depressive illness, a
      marker at the DDC locus which has been mapped to 7p11-p13 and 10 microsatellite
      markers covering chromosome 7q11-p15. No evidence of linkage was found assuming a
      dominant or a recessive mode of inheritance. We have earlier reported evidence
      against linkage between manic depressive illness and tyrosine hydroxylase and
      dopamine beta-hydroxylase. Mutations of major importance in the genes encoding
      the three enzymes involved in the synthesis of dopamine and noradrenaline seem
      less likely in the families we have studied. Further investigations of genetic
      and other pathophysiological mechanisms in relation to the monoamine hypotheses
      for manic depressive illness are still of relevance. There is a need for further
      linkage and association studies as well as a search for possible mutations in the
      relevant genes involved in the monoaminergic pathways to clarify their possible
      role in the aetiology of manic depressive illness.

PMID- 8750359
TI  - Dopamine D1, D2 and D3 receptor genes in alcohol dependence.
AB  - Hereditary factors play a substantial role in the etiology of alcohol dependence.
      Alcohol mediates its reinforcing effects by an activation of the mesolimbic
      dopamine system. These findings suggest that the genes encoding the dopamine
      receptor (DR) subtypes represent high-ranking candidates for susceptibility genes
      to addictive disorders. Our present population-based association study
      investigated whether sequence variants of the dopamine D1, D2 and D3 receptor
      genes confer susceptibility to alcohol dependence in 278 alcoholics, and
      clinically more homogeneous subgroups ascertained through positive family
      history, early age at onset, delirium, withdrawal seizures and antisocial
      tendencies. No evidence for an allelic association was found for the PCR-based
      TaqA RFLP fo the DRD2 gene and a Bsp1286I RFLP of the DRD1 gene. Without
      correction for multiple testing, we found a significantly increased allele
      frequency of a common DRD3 gene variant expressing a serine at position 9 in the
      extracellular N-terminal part of the receptor protein in 55 alcohol-dependent
      individuals with delirium (chi 2 = 4.1, df = 1, p = 0.042). Further studies have
      to examine whether this amino acid substitution or a nearby mutation confers
      genetic susceptibility to at least a subgroup of alcohol-dependent individuals
      with delirium.

PMID- 8750360
TI  - Genetic association between alleles of pancreatic phospholipase A2 gene and
      bipolar affective disorder.
AB  - Chromosome 12q is a region of interest for the genetics of bipolar affective
      disorder because of reports of apparent cosegregation between this disorder and
      Darier's disease in a small number of families. Findings from a recent linkage
      study suggest that this chromosomal region may contain a susceptibility gene for
      bipolar affective disorder. We have found evidence of an allelic association
      between bipolar disorder and a marker at the pancreatic phospholipase A2 gene
      (PLA2A) in this region (p < or = 0.01). These results are consistent with the
      linkage study, and warrant additional investigations.

PMID- 8750361
TI  - Anticipation in Swedish families with schizophrenia.
AB  - Nineteen parent-offspring pairs obtained from 14 two-generation families with
      available medical records and diagnosis of schizophrenia were studied to compare
      the ages of onset of the parent generation with those of the offspring
      generation. The mean age of onset for the parent generation was 37.3 +/- 6.0
      years and for the offspring generation was 20.8 +/- 4.4. The mean difference was
      thus 16.5 +/- 6.2, suggesting the occurrence of anticipation in schizophrenia (p
      < 0.001). Although some ascertainment biases (like reduced fertility in early
      onset parents or early detection of symptoms in offsprings of affected parents)
      may partially contribute to the occurrence of anticipation, this study replicates
      recent reports of anticipation in several neuropsychiatric disorders, some of
      which have been shown to be associated with unstable expansions of trinucleotide
      repeats in the genomic DNA.

PMID- 8750362
TI  - Clinical pharmacology of antiepileptic drug use: "clinical pearls about the
      perils of patty".
AB  - This Clinical Pharmacology Problem Solving (CPPS) Unit is for use with fourth- or
      fifth-year pharmacy students and third- or fourth-year medical students during
      conferences held when they are taking either a rotation in Neurology or Clinical
      Pharmacology. It may also be used for house staff teaching of residents in
      Neurology, Pediatrics, Internal Medicine, and Family Practice and fellows in
      Clinical Pharmacology. This material was prepared for a Teaching Clinic in
      Clinical Pharmacology taught by Claire M. Lathers, PhD, FCP, Hugh J. Burford,
      PhD, FCP, and Cedric M. Smith, MD, FCP, and sponsored by the American College of
      Clinical Pharmacology, September 19-20, 1992, Washington, DC. This workbook
      includes: (1) an introduction to the Clinical Pharmacology Problem Solving (CPPS)
      Unit; (2) the learning objectives of the clinical simulation; (3) a pretest; (4)
      four clinical episodes occurring over many years in the life of a patient; (5)
      answers to the pretest; (6) a posttest; (7) answers to the posttest.

PMID- 8750363
TI  - Concentration-guided strategies in drug development: experience with a
      cyclosporine analog in transplantation.
AB  - A concentration-guided study was designed to maintain adequate immunosuppression
      and avoid excessive drug exposure while determining steady-state relative
      bioavailability of two cyclosporine G (CyG) oral formulations in stable renal
      transplant patients. In period I (week 1), 26 patients taking cyclosporine A
      (CyA)-based immunosuppressive regimens entered the study. Doses were titrated to
      maintain trough concentrations within a predefined range, as measured by
      fluorescence polarization immunoassay (FPIA). Patients were given an oral
      solution of CyG in period II (weeks 2-3), and a microemulsion capsule formulation
      of CyG in period III (weeks 4-5), with dose titration as necessary to achieve
      trough concentrations in a predefined range, as measured by FPIA. Full
      pharmacokinetic profiles were obtained on the last day of each study period.
      Treatment with CyA was reinitiated in period IV (week 6) at the same doses as at
      study entry. All blood samples were analyzed at the conclusion of the study using
      CyG- and CyA-specific high-performance liquid chromatography (HPLC). When
      changing from oral solution to capsule for CyG, an average 19% dose reduction was
      necessary to compensate for the elevated trough concentrations resulting from the
      increased bioavailability of the capsule formulation. The concentration-guided
      strategy was successful in avoiding over-exposure, and resulted in comparable
      values for area under the concentration-time curve (AUC) for both formulations of
      CyG. Dose normalization of the pharmacokinetic parameters subsequently allowed
      calculation of the relative bioavailability. Specifically, a faster rate and
      greater extent of CyG absorption from the capsule than the oral solution were
      manifested as a slightly earlier time to peak concentration (tmax), an average
      44% increase in the maximum concentration (Cmax), and an average 29% increase in
      AUC. This experience demonstrated that a concentration-guided trial design
      allowed a drug development question for a compound with a narrow therapeutic
      index to be addressed safely and directly in the target patient population.

PMID- 8750364
TI  - Gender differences in exercise and recovery blood pressure responses in normal
      volunteers given diltiazem.
AB  - This preliminary phase I study was conducted in healthy volunteers to determine
      whether gender differences exist in the hemodynamic effects of diltiazem at rest,
      during exercise, and after exercise. At comparable serum concentrations of the
      drug, women demonstrated lower systolic and diastolic pressure during exercise
      and after exercise. ST slope after diltiazem administration in women became less
      positive during exercise and was gender specific. Heart rate and P-R interval
      changes were not gender dependent. Results of this study demonstrate that some
      hemodynamic responses to diltiazem are gender specific while others are not. It
      indicates that direct comparison studies may be required to detect such
      differences. In healthy women, hypotension after exercise and the effects of
      diltiazem are more synergistic than in men. Such a gender difference in response
      may be an important consideration in determining the correct dosages of this drug
      for treatment of hypertension.

PMID- 8750365
TI  - Ramipril decreases chlorthalidone-induced loss of magnesium and potassium in
      hypertensive patients.
AB  - A double-blind clinical trial was conducted to compare the efficacy of and
      electrolyte changes caused by ramipril-chlorthalidone combination treatment (5 mg
      + 25 mg) and chlorthalidone monotherapy (25 mg daily) in patients with
      hypertension. After a 4-week placebo period, 32 patients (mean age, 51 +/- 9
      years) with essential hypertension (average blood pressure of 181.4/104.5 +/-
      13.0/6.9 mmHg) were randomly assigned to receive combination therapy (group A, n
      = 17) or monotherapy (group B, n = 15). After 12 weeks of active treatment,
      systolic and diastolic blood pressure decreased by 16.1% and 13%, respectively,
      for patients taking combined therapy, and by 12.7% and 9.8%, respectively, for
      patients taking monotherapy. The difference was significant for between-group
      comparisons. There were no changes in serum sodium concentration, but a
      significant similar increase in 24-hour urinary sodium excretion was seen in both
      groups. Serum calcium levels increased slightly and 24-hour urinary calcium
      excretion decreased significantly in both groups, probably due to chlorthalidone
      administration. Serum potassium levels increased slightly in group A (from 4.16
      +/- 0.39 mmol/L to 4.30 +/- 0.42 mmol/L) and decreased slightly in group B (from
      4.18 +/- 0.32 mmol/L to 3.99 +/- 0.49 mmol/L). Urinary potassium excretion did
      not change significantly in group A, but increased by approximately 15% in group
      B. There was a decrease in 24-hour urinary magnesium excretion (from 4.01 +/-
      1.24 mmol/24 hours to 3.50 +/- 0.93 mmol/24 hours) in group A and an increase
      (from 3.49 +/- 0.98 mmol/24 hours to 4.35 +/- 1.12 mmol/24 hours) in group B. At
      the end of the trial these changes were significant in between-group comparisons.
      Consistent with the previously shown amelioration by ramipril of thiazide-induced
      metabolic side-effects, ramipril appears to improve magnesium balance during
      cotreatment with chlorthalidone.

PMID- 8750366
TI  - 5-fluorouracil modulates the toxicity of high dose methotrexate.
AB  - Pretreatment with 5-fluorouracil (FU) attenuated the toxicity of high dose
      methotrexate (MTX) in in vitro and in vivo models. Because dose intensification
      of the MTX reversed the fluoropyrimidine antagonism of MTX activity in these
      models, administering FU before the MTX offered the potential advantage of MTX
      dose intensity and low toxicity without the confounding effects of leucovorin
      rescue. The current study was conducted to determine the maximum dose of MTX
      tolerated after a priming dose of FU without leucovorin rescue, and to determine
      the toxicities of this combination. Subjects (n = 42) received a constant dose of
      FU followed in 2 hours by MTX; treatment was repeated every 3 weeks. Subjects
      initially received five doses of leucovorin (10 mg/m2 every 6 hours); this was
      reduced to two doses, then to zero doses (no rescue) if less than grade 2
      toxicity occurred in prior treatments. Cohorts of subjects received escalating
      doses of MTX in a Fibonacci fashion. At the 1250 mg/m2 dose level, almost all
      previously untreated subjects tolerated the elimination of leucovorin rescue,
      without the occurrence of severe toxicity; this was 6 to 8 times the MTX dose
      that generally requires leucovorin rescue to avoid severe and lethal toxicity.
      The 24- and 48-hour MTX levels were at a level that usually requires leucovorin
      rescue. Previously treated subjects were less tolerant; 400 mg/m2 of MTX was the
      approximate maximum tolerated dose. Prior FU exposure appeared to protect tissues
      normally susceptible to MTX toxicity, and allowed safe administration of high
      dose MTX without leucovorin rescue.

PMID- 8750367
TI  - Intrapulmonary and systemic pharmacokinetics of aerosolized pentamidine used for
      prophylaxis of pneumocystis carinii pneumonia in patients infected with the human
      immunodeficiency virus.
AB  - A study was conducted to determine the intrapulmonary and systemic
      pharmacokinetics of aerosolized pentamidine prophylaxis (APP) in patients
      infected with human immunodeficiency virus (HIV). 151 patients received high-dose
      (300 mg twice a month or 600 mg once a month) APP as part of a previously
      published clinical trial, and 29 additional patients received standard-dose (300
      mg once a month) APP. Serial blood samples were obtained from the first cohort:
      577 samples were obtained from 76 patients in the group given 600 mg once a
      month, and 554 blood samples were obtained from 75 patients in the group given
      300 mg twice a month. In 9 of the 151 patients, bronchoscopy and tri-lobar (right
      upper, middle, and lower lobe) bronchoalveolar lavage (BAL) were performed 6 and
      12 months after initiation of APP. Unilobar (right middle lobe) BAL was performed
      in the 29 patients infected with HIV who underwent bronchoscopy for diagnostic
      purposes. Pentamidine was measured using a chromatographic (HPLC) assay. The
      concentrations (mean +/- SD) of pentamidine in plasma in the groups given 300 mg
      twice a month and 600 mg once a month were 5.3 +/- 6.1 ng/mL and 8.8 +/- 9.6
      ng/mL, respectively, and accumulation did not occur. The BAL supernatant and
      alveolar cell pentamidine concentrations were not significantly different in the
      3 lobes and ranged from 16.5 +/- 7.7 ng/mL to 29.2 +/- 19.5 ng/mL and 1255 +/-
      1142 ng/mg protein to 1572 +/- 1161 ng/mg protein in the group given 300 mg twice
      a month; and from 5.5 +/- 2.9 ng/mL to 9.4 +/- 7.7 ng/mL and 339 +/- 201 ng/mg
      protein to 571+/- 681 ng/mg protein in the group given 600 mg once a month. The
      intropulmonary concentrations of pentamidine at 6 and 12 months were not
      significantly different. In 18 of the 29 patients who received 1 to 7 prior
      monthly doses of standard APP, drug concentrations in BAL increased linearly (y =
      2.05x) with the number of doses administered before bronchoscopy. These data
      indicate that intrapulmonary drug concentrations continue to increase for
      approximately 6 months after the initiation of APP, at which time steady state is
      achieved, and that administration of high dose APP is probably safe.

PMID- 8750368
TI  - Pharmacokinetics, absolute bioavailability, and absorption characteristics of
      lamivudine.
AB  - Lamivudine is a novel cytosine nucleoside analog, reverse transcriptase inhibitor
      that has shown activity against human immunodeficiency virus (HIV) types 1 and 2
      and hepatitis B virus in vitro. This study was conducted to compare the absolute
      bioavailability, pharmacokinetics, and absorption characteristics of oral
      solution, 100-mg capsule, and 100-mg tablet formulations of lamivudine with those
      of intravenous lamivudine. Twelve patients with HIV were enrolled in a single
      center, randomized, open-label, four-way cross-over study. Treatment arms
      consisted of 100 mg intravenous lamivudine (administered over 1 hour), 100 mg
      oral lamivudine (1 mg/mL), a 100-mg capsule, and a 100-mg tablet, each followed
      by a 3- to 14-day washout period. Serial blood samples over 24 hours were
      obtained after each dose administration. Serum concentration data were analyzed
      to determine pharmacokinetic parameter estimates including area under the curve
      (AUC), terminal half-life (t1/2), mean residence time (MRT) for each formulation,
      systemic clearance, oral clearance, and apparent volume of distribution (Vd).
      Absolute bioavailability and in vivo mean absorption time (MAT) and mean
      dissolution time (MDT) were calculated for the oral formulations. Deconvolution
      techniques were used to calculate the input rate for the oral solution, capsule,
      and tablet. The two one-sided t test was used to determine bioequivalency among
      oral formulations with respect to logarithmic transformed estimates of AUC and
      maximum peak concentration (Cmax). Mean (CV) systemic clearance and Vdss after
      intravenous administration of lamivudine were 22.6 L/h (15%) and 99 L (28%),
      respectively; mean t1/2 ranged from 8.41 to 9.11 hours for all formulations; and
      MRT ranged from 4.42 to 5.77 hours for all formulations. Mean absolute
      bioavailability ranged from 86% to 88% for the oral solution, capsule, and
      tablet. All oral formulations were considered bioequivalent for AUC and Cmax. The
      MAT was 1.32 hour for the oral solution, and MDT was 0.03 and -0.11 hours for the
      capsule and the oral solution, respectively. The oral formulations of lamivudine
      examined in this study demonstrated acceptable bioavailability for oral
      administration. The solid oral formulations (capsule and tablet) show rapid
      dissolution properties with an absorption rate similar to or exceeding those
      observed with the oral solution. This suggests that dissolution is not an
      important factor for the rate of absorption of lamivudine. The use of
      deconvolution techniques using PCDCON provides valuable insight into the
      absorption characteristics of lamivudine.

PMID- 8750369
TI  - Variability in the pharmacokinetics and pharmacodynamics of low dose aspirin in
      healthy male volunteers.
AB  - Data describing the pharmacokinetics and pharmacodynamics of low dose aspirin
      (acetylsalicylic acid; ASA) are limited. This single-center study was designed to
      determine the rate and extent of oral absorption of 80-mg ASA tablets in healthy,
      young male subjects and to assess the intra- and inter-subject variability of ASA
      pharmacokinetics and platelet aggregation effects. Ten subjects each received a
      single, open-label, oral 80-mg ASA dose on three separate days. Each dose was
      separated by a 2-week washout interval. Blood samples for pharmacokinetic
      determinations of ASA and its metabolite, salicylic acid (SA) and platelet
      aggregation studies were obtained at scheduled timepoints before and up to 24
      hours after each dose. Peak plasma ASA levels of 1 microgram/mL were achieved
      within 30 minutes. Peak plasma SA levels of approximately 4 micrograms/mL were
      attained in 1 hour. The terminal half-lives (t1/2) of ASA and SA were 0.4 and 2.1
      hours, respectively. Both ASA and SA pharmacokinetics and the platelet
      aggregation response to ASA exhibited considerable intra- and inter-subject
      variability. Inhibition of platelet aggregation was found to relate with ASA area
      under the plasma concentration versus time curve (AUC).

PMID- 8750370
TI  - Pharmacokinetic and pharmacodynamic evaluation of triamcinolone acetonide after
      intravenous, oral, and inhaled administration.
AB  - Triamcinolone acetonide (TCA) is a corticosteroid that is frequently used in the
      treatment of asthma. After inhalation, TCA can become systemically available when
      the inhaled formulation is swallowed, causing undesirable systemic effects. A
      clinical study was conducted to determine the systemic side effects of TCA after
      intravenous (2 mg as phosphate ester), oral (5 mg), and inhaled (2 mg)
      administration. Blood samples were collected at appropriate times over 24 hours,
      and TCA concentrations in plasma were measured by high-performance liquid
      chromatography and radioimmunoassay. Free drug concentrations were determined by
      ultrafiltration for correlating pharmacokinetics and pharmacodynamics. The free
      fraction of TCA (+/- standard deviation) was 29.0 +/- 1.3% and was independent of
      the investigated concentration range up to 1,000 ng/mL. Pharmacodynamic
      parameters were determined by monitoring lymphocytes, granulocytes, and cortisol.
      Pharmacokinetic/pharmacodynamic modeling was performed using a modified Emax
      model for lymphocytes and granulocytes. A novel linear release rate model was
      used to characterize the cortisol data. The E50 values determined from all three
      pharmacodynamic endpoints were not significantly different for the three
      treatments, indicating that these effects can be explained based on systemic
      steroid concentrations.

PMID- 8750371
TI  - The dose proportionality of the pharmacokinetics of ardeparin, a low molecular
      weight heparin, in healthy volunteers.
AB  - Ardeparin is a low molecular weight heparin currently being evaluated as an
      antithrombotic agent. The objective of this investigation was to assess the
      effects of dose on the pharmacokinetics of ardeparin after subcutaneous
      administration. Eighteen healthy subjects received doses of 30 U/kg, 60 U/kg, and
      100 U/kg antifactor Xa (aXa) of ardeparin by subcutaneous injection. Plasma
      antifactor IIa (aIIa) activity levels after the 30- and 60-U/kg doses of
      ardeparin were too low to reliably characterize the disposition of the drug.
      However, the pharmacokinetics of ardeparin could be characterized by using
      pharmacodynamic measurements of plasma aXa activity. The rate of absorption of
      ardeparin after subcutaneous administration did not change with increasing dose.
      The volume of distribution (Vd) of ardeparin was small, reflecting minimal
      distribution outside the intravascular space, and was independent of dose. The
      total clearance of ardeparin, however, decreased with increasing dose, and half
      life (t1/2) was prolonged at the higher doses. Within the observed dose range, a
      doubling of the ardeparin dose resulted in an area under the plasma aXa activity
      versus-time curve (AUC) that was approximately 25% greater than expected on the
      basis of linear disposition. The differences in AUC and clearance between the
      three doses suggest that the mechanism of elimination of ardeparin is saturable.

PMID- 8750372
TI  - Absence of a pharmacokinetic interaction between losartan and
      hydrochlorothiazide.
AB  - To support the use of a combination of losartan, a highly specific and selective
      AT1 angiotensin II receptor antagonist, and hydrochlorothiazide for treatment of
      hypertension, a pharmacokinetic drug interaction study was conducted. In this
      open-label, randomized, three-period, crossover study, patients with mild to
      moderate hypertension received a 12.5-mg tablet of hydrochlorothiazide, a 50-mg
      losartan tablet, or a combination tablet of 12.5 mg of hydrochlorothiazide and 50
      mg of losartan for 7 days. Twelve patients (age range, 35-55 years; mean age, 44
      years) were allocated to treatment. Drug interactions were evaluated by comparing
      the 24-hour area under the concentration-time curve (AUC24) for losartan and its
      active metabolite, E-3174, when losartan (50 mg) was given alone or in
      combination with 12.5 mg hydrochlorothiazide. The urinary recovery over the 24
      hour period of hydrochlorothiazide was compared for hydrochlorothiazide (12.5 mg)
      given alone or in combination with 50 mg losartan. A clinically significant
      interaction was defined as a treatment difference of more than 35%. There was no
      evidence of a clinically significant effect of hydrochlorothiazide on the
      pharmacokinetics of losartan or E-3174, as the geometric mean AUC24 ratio (90%
      confidence interval [CI]) was 1.02 (0.95, 1.09) for losartan and 1.02 (0.96,
      1.09) for E-3174. Based on urinary recovery over a 24-hour period of
      hydrochlorothiazide, losartan did not affect the pharmacokinetics of
      hydrochlorothiazide, as the geometric mean ratio of urinary hydrochlorothiazide
      recovery (90% CI) was 0.898 (0.79, 1.20). There was a minor (17%) decrease in the
      AUC24 of hydrochlorothiazide after administration of the combination tablet.
      Coadministration of hydrochlorothiazide and losartan was well tolerated.

PMID- 8750373
TI  - Distance from the Primary Health Center: a GIS method to study geographical
      access to health care.
AB  - Aerial distance from the dependent Primary Health Center is a crude but objective
      measure of geographical accessibility to Primary Health care facilities. This
      report describes a method for calculation of distances between the PHC and the
      population it serves using the data available from the local health authorities
      and the Swedish Central Statistical Bureau. The Swedish annual population
      registration records of 1991 and the property register available with the Central
      Statistical Bureau of Sweden formed the main data sources. By coupling the
      address in the population register to the property register each individual was
      mapped to the centroid of a property. The location of the PHCs as well as the
      areas covered by each were obtained from the local health authorities and mapped.
      By intersecting the population coverage with the PHC coverage the population for
      each PHC area was identified. Subsequently the distance to the PHC was calculated
      for each individual (property centroid). The population maps so generated can be
      linked to other databases to visualize and analyze the spatial dimension of
      health and disease. The methodology can be adapted for use with postal code
      districts, census enumeration tracts, or any other small area.

PMID- 8750374
TI  - A method for creating an enormous medical knowledge base.
AB  - Using a high-density knowledge representation method designed by us, we have
      developed the Enormous Knowledge Base of Disease Diagnosis Criteria (EKBDDC). It
      contains diagnostic criteria of 1001 diagnostic entities and describes nearly
      4000 items of diagnostic indicators. It is the core of a huge medical project-
      Electronic Brain Medical Erudite (EBME). This enormous knowledge base was
      implemented initially on a low-cost popular microcomputer, which can aid in
      prompting of typical disease and in teaching of diagnosis. This knowledge base
      will be constantly expanded and adapted to the need of diagnosing of atypical
      diseases. By means of a software interface it will be connected with the
      international medical information systems. We have also explored an assembling
      technique of medical knowledge base. To test the behavior of EBME we performed a
      series of trials with a total of 815 cases. The diagnostic accordance rates were
      89.7, 89.4, and 85%, respectively. It demonstrated that this system should be
      improved before clinical application.

PMID- 8750375
TI  - An automated patient registration and treatment randomization system.
AB  - Centralized patient registration and treatment randomization for multicenter
      clinical trials has many advantages over other approaches. Our Automated Patient
      Registration and Treatment Randomization system is a fully automated Interactive
      Voice Response, microcomputer-based application which can operate unattended and
      is continuously available to provide patient registration and treatment
      randomization. Several techniques are employed to ensure security of the system
      and validity and accuracy of the data. Several randomization methods were
      implemented to support different study designs including balanced block
      randomization, stratified permuted block scheme, and a sophisticated
      randomization design based on the minimization method and Zelen's adaptive
      randomization method for institution balancing.

PMID- 8750376
TI  - A system to project injury and illness incidence during military operations.
AB  - Modeling of medical resource requirements during military operations requires
      projections of disease and non-battle injury (DNBI) and wounded-in-action (WIA)
      rates. Historical data were extracted from unit diaries of infantry and support
      troops deployed during four previous combat engagements. A planning tool
      (FORECAS) was developed that uses the statistical distributions of DNBI and WIA
      incidence from previous operations to simulate injury and illness arrival rates
      under future scenarios. Output of the simulated data reflects the nuances of the
      empirical data.

PMID- 8750377
TI  - Financial effect of clinical decisions: case study of a dialysis center.
AB  - The purpose of this study was to specify the financial effect of clinical
      decisions in a dialysis center. A consecutive sample of 14,343 outpatient
      hemodialysis treatments (OHD), 16,111 continuous ambulatory peritoneal dialysis
      (CAPD), and 4,513 chronic cycler-assisted peritoneal dialysis (CCPD) days of
      treatment was analyzed. An activity-based cost calculation method was applied to
      the analysis of alternative treatments (service bundles). The weekly cost of OHD
      was higher ($338 versus $241/$242), and the contribution margin (reimbursement
      minus total cost) of CAPD/CCPD was much greater ($.48 versus $148/$147 per
      patient week). Clinical decision-making had an influence on less than 6.8% of OHD
      and 45.4%/46.6% of CAPD/CCPD related expenses. In comparison to activity-based
      cost calculation, conventional methods overestimated the overhead expense of CAPD
      by 3-48%. This study documented that most cost control opportunities reside in
      the usual process of care and less can be influenced by a direct interference
      with the patient-physician contacts. Paying for 1 week of renal replacement
      (capitation) could simplify the process of reimbursement and cost tracking.

PMID- 8750378
TI  - A quantitative color recognition measurement system using multimedia computer
      environment.
AB  - We developed a quantitative measurement system that tests the degree of dysgnosia
      resulting from Obsessive-Compulsive Disorder (OCD). The system outputs a
      stimulation word that had been set in advance using the voice output facility of
      the personal computer, then displays a color chart and waits for input from the
      subject. When the subject touches the CRT screen or clicks the mouse, the system
      records the response time and coordinates of input position. There were 30
      stimulation words in the system. After 30 measurements of response time and input
      coordinates, the system outputs a results file that includes each response time
      and input coordinates. This test is easier and simpler than other psychological
      tests such as MMPI. The influence of the examiner can be reduced to the minimum
      with this system because it is a computer-based automatic measurement system. To
      use the computer system, an examiner can easily standardize the environment of
      the illumination, etc. Moreover, the system can save labor in testing, and can
      manage large amounts of data easily using the file management facility.

PMID- 8750379
TI  - The significance of smooth and striated muscles in the sphincter function of the
      urethra in healthy women.

PMID- 8750380
TI  - Analyzing finasteride data.
AB  - Published data on the safety and efficacy of finasteride in the treatment of
      benign prostatic hyperplasia are studied and compared with published conclusions.
      The need for publishing correlation studies of both the benefits and side
      effects, to allow for informed physician and patient decisions, is detailed.

PMID- 8750381
TI  - Is detrusor instability in elderly males related to the grade of obstruction?
AB  - Analysis of 185 consecutive patients with BPH revealed concomitant detrusor
      instability in 20% of the patients. Of all patients 30.9% were not obstructed,
      51.8% were moderately obstructed and 17.3% were severely obstructed. Patients
      with detrusor instability during filling cystometry revealed no differences in
      average age, prostate volume or symptoms. Mean filling cystometry parameters
      revealed earlier sense of urge correlating with higher pressures at lower volumes
      in patients with detrusor instability. Pressure-flow analysis showed no
      differences between the patients with and without detrusor instability in bladder
      outflow obstruction parameters. Further analysis, however, revealed that the
      prevalence of patients with detrusor instability reaches a "steady state" at a
      moderate level of obstruction. On clinical epidemiological grounds, the
      conclusion is made that detrusor instability is developing in the early phase of
      obstruction. Probably detrusor instability and bladder outflow obstruction are
      concomitant, due to the aging process in many of these patients.

PMID- 8750382
TI  - Toward a new classification of overactive bladders.
AB  - Based on a large retrospective series, this study compares the International
      Continence Society's (ICS) classification of overactive bladders and a functional
      subtyping of our own, founded on clinical and urodynamic parameters. Functionally
      identical symptoms and urodynamic patterns were found within the Detrusor
      Hyperreflexia as well as the Unstable Detrusor categories. There are strong
      arguments for a revision of the current ICS classification system.

PMID- 8750383
TI  - Urodynamic and other effects of tolterodine: a novel antimuscarinic drug for the
      treatment of detrusor overactivity.
AB  - Tolterodine, a novel compound intended for treatment of urgency and urge
      incontinence, has been characterized as a potent muscarinic receptor antagonist
      in pharmacological in vitro and in vivo studies. In cats, tolerodine was shown to
      reduce bladder pressure at doses significantly lower than those affecting
      salivation. To predict clinical effectiveness, an open pilot study was performed
      in healthy male volunteers. Efficacy was measured by cystometry and by
      spontaneously reported effects after administration of a single oral dose of
      tolterodine, 6.4 mg, given as a water solution. Tolterodine had distinct
      inhibitory effects on urinary bladder function, both at 1 and 5 hours post-dose.
      At 1 hour, but not at 5 hours post-dose tolterodine also significantly reduced
      stimulated salvation. In addition to the objectively demonstrated changes in
      urodynamic parameters, most volunteers experienced voiding difficulties. No
      significant changes in blood pressure, heart rate, or near point of accommodation
      were registered. Tolterodine, in the dosage used, was both objectively and
      subjectively shown to exert a marked inhibitory effect on micturition in healthy
      subjects, and the data suggest a more pronounced effect on bladder function than
      on salivation.

PMID- 8750384
TI  - Irritable bladder syndrome in an animal model: a continuous monitoring study.
AB  - Irritable bladder syndrome (IBS) was induced in four female African green monkeys
      (Cercopithecus aethiops) by the use of intravesical instillation of acetone. The
      animals were housed in a modified metabolic cage for continuous micturition
      monitoring, and two uroflowmeters connected to a remote PC monitored the
      frequency, voided volumes, and peak flows. Before and after, urea absorption
      studies and urodynamics were obtained for each animal. Urea absorption increased
      significantly after acetone instillation and returned to baseline after 4 weeks
      (26 to 66 to 32%). Intravesical acetone instillation produced marked effects on
      bladder physiology in the first week. Bladder compliance dropped from a baseline
      of 10.47 to 0.58 ml/cm H2O. The voiding pattern changed from a normal pattern
      with a mean voided volume of 17.58 ml into marked increase in frequency and
      dribbling pattern with few voids (mean = 5.03 ml). Systematic behavioral
      observations were carried out for 4 hours per day utilizing an observation
      program on a laptop computer. Activity patterns, attention, sterotypic behaviors,
      and self-directed activities were recorded for each monkey. The animals
      demonstrated decreased frequency of activity and increased frequency in self
      directed activities (groom, scratch), behaviors consistent with an animal
      experiencing pain or discomfort. The findings suggested that IBS induction in
      monkeys is feasible and produces a clinical picture similar to interstitial
      cystitis in humans. It offers a suitable animal model to enhance the
      understanding of voiding dysfunction with its neural pathways and to test the
      different therapeutic modalities to control IBS.

PMID- 8750385
TI  - Regarding "Significance of rectal contractions noted on multichannel
      urodynamics," Combs AJ, Nitti VW (1995): Neurourology and Urodynamics 14:73-80.

PMID- 8750386
TI  - The World Wide Web: a review of an emerging internet-based technology for the
      distribution of biomedical information.
AB  - The Internet is rapidly evolving from a resource used primarily by the research
      community to a true global information network offering a wide range of databases
      and services. This evolution presents many opportunities for improved access to
      biomedical information, but Internet-based resources have often been difficult
      for the non-expert to develop and use. The World Wide Web (WWW) supports an
      inexpensive, easy-to-use, cross-platform, graphic interface to the Internet that
      may radically alter the way we retrieve and disseminate medical data. This paper
      summarizes the Internet and hypertext origins of the WWW, reviews WWW-specific
      technologies, and describes current and future applications of this technology in
      medicine and medical informatics. The paper also includes an appendix of useful
      biomedical WWW servers.

PMID- 8750387
TI  - HCFA's health care quality improvement program: the medical informatics
      challenge.
AB  - The peer-review organizations (PROs) were created by Congress in 1984 to monitor
      the cost and quality of care received by Medicare beneficiaries. In order to do
      this, the Health Care Financing Administration (HCFA) contracted with the PROs
      through a series of contracts referred to as "Scopes of Work." Under the Fourth
      Scope of Work, the HCFA initiated the Health Care Quality Improvement Program
      (HCQIP) in 1990, as an application of the principles of continuous quality
      improvement. Since then, the PROs have participated with health care providers in
      cooperative projects to improve the quality of primarily inpatient care provided
      to Medicare beneficiaries. Through HCFA-supplied administrative data and clinical
      data abstracted from patient records, the PROs have been able to identify
      opportunities for improvements in patient care. In May 1995, the HCFA proposed a
      new Fifth Scope of Work, which will shift the focus of HCQIP from inpatient care
      projects to projects in outpatient and managed care settings. This article
      describes the HCQIP process, the types of data used by the PROs to conduct
      cooperative projects with health care providers, and the informatics challenges
      in improving the quality of care received by Medicare beneficiaries.

PMID- 8750388
TI  - Willow: a uniform search interface.
AB  - The objective of the Willow Project is to develop a uniform search interface that
      allows a diverse community of users to retrieve information from heterogeneous
      network-based information resources. Willow separates the user interface from the
      database management or information retrieval system. It provides a graphic user
      interface to a variety of information resources residing on diverse hosts, and
      using different search engines and idiomatic query languages through networked
      based client-server and Transmission Control Protocol/Internet Protocol (TCP/IP)
      protocols. It is based on a "database driver'' model, which allows new database
      hosts to be added without altering Willow itself. Willow employs a multimedia
      extension mechanism to launch external viewers to handle data in almost any form.
      Drivers are currently available for a local BRS/SEARCH system and the Z39.50
      protocol. Students, faculty, clinicians, and researchers at the University of
      Washington are currently offered 30 local and remote databases via Willow. They
      conduct more than 250,000 sessions a month in libraries, medical centers and
      clinics, laboratories, and offices, and from home. The Massachusetts Institute of
      Technology is implementing Willow as its uniform search interface to Z39.50
      hosts.

PMID- 8750389
TI  - Implementation of physician order entry: user satisfaction and self-reported
      usage patterns.
AB  - OBJECTIVES: To evaluate user satisfaction, correlates of satisfaction, and self
      reported usage patterns regarding physician order entry (POE) in one hospital.
      DESIGN: Surveys were sent to physician and nurse POE users from medical and
      surgical services. RESULTS: The users were generally satisfied with POE (mean =
      5.07 on a 1 to 7 scale). The physicians were more satisfied than the nurses, and
      the medical staff were more satisfied than the surgical staff; satisfaction
      levels were acceptable (more than 3.50) even in the less satisfied groups.
      Satisfaction was highly correlated with perceptions about POE's effects on
      productivity, ease of use, and speed. POE features directed at improving the
      quality of care were less strongly correlated with satisfaction. The physicians
      valued POE's off-floor accessibility most, and the nurses valued legibility and
      accuracy of POE orders most. Some features, such as off-floor ordering, were
      perceived to be highly useful and reported to be frequently used by the
      physicians; while other features, such as "quick mode'' ordering and personal
      order sets, received little self-reported use. CONCLUSIONS: Survey of POE users
      showed that satisfaction with POE was good. Satisfaction was more correlated with
      perceptions about POE's effect on productivity than with POE's effect on quality
      of care. Physicians and nurses constitute two very different types of users,
      underscoring the importance of involving both physicians and nonphysicians in POE
      development. The results suggest that development efforts should focus on
      improving system speed, adding on-line help, and emphasizing quality benefits of
      POE.

PMID- 8750390
TI  - An expert system for performance-based direct delivery of published clinical
      evidence.
AB  - OBJECTIVE: To develop a system for clinical performance improvement through rule
      based analysis of medical practice patterns and individualized distribution of
      published scientific evidence. METHODS: The Quality Feedback Expert System (QFES)
      was developed by applying a Level-5 expert system shell to generate clinical
      direct reports for performance improvement. The system comprises three data and
      knowledge bases: 1) a knowledge base of measurable clinical practice parameters;
      2) a practice pattern database of provider-specific numbers of patients and
      clinical activities; and 3) a management rule base comprising "redline rules"
      that identify providers whose practice styles vary significantly. Clinical direct
      reports consist of a table of practice data highlighting individual utilization
      vs recommendation and selected pertinent statements from medical literature.
      RESULTS: The QFES supports integration of recommendations from several guidelines
      into a comprehensive and measurable quality improvement plan, analysis of actual
      practice patterns and comparison with accepted recommendations, and generation of
      a confidential individualized direct report to those who significantly deviate
      from clinical recommendations. The feasibility of the practice pattern analysis
      by the QFES was demonstrated in a sample of 182 urinary tract infection cases
      from a primary care clinic. In a set of clinical activities, four
      questions/procedures were associated with significant (p < 0.001) and unexplained
      variation. CONCLUSION: The QFES provides a flexible tool for the implementation
      of clinical practice guidelines in diverse and changing clinical areas without
      the need for special program development. Preliminary studies indicate utility in
      the analysis of clinical practice variation and deviations. Using data obtained
      through a retrospective chart audit, the QFES was able to detect overutilization,
      and to identify nonrandom differences in practice patterns.

PMID- 8750391
TI  - Portability issues for a structured clinical vocabulary: mapping from Yale to the
      Columbia medical entities dictionary.
AB  - OBJECTIVE: To examine the issues involved in mapping an existing structured
      controlled vocabulary, the Medical Entities Dictionary (MED) developed at
      Columbia University, to an institutional vocabulary, the laboratory and pharmacy
      vocabularies of the Yale New Haven Medical Center. DESIGN: 200 Yale pharmacy
      terms and 200 Yale laboratory terms were randomly selected from database files
      containing all of the Yale laboratory and pharmacy terms. These 400 terms were
      then mapped to the MED in three phases: mapping terms, mapping relationships
      between terms, and mapping attributes that modify terms. RESULTS: 73% of the Yale
      pharmacy terms mapped to MED terms. 49% of the Yale laboratory terms mapped to
      MED terms. After certain obsolete and otherwise inappropriate laboratory terms
      were eliminated, the latter rate improved to 59%. 23% of the unmatched Yale
      laboratory terms failed to match because of differences in granularity with MED
      terms. The Yale and MED pharmacy terms share 12 of 30 distinct attributes. The
      Yale and MED laboratory terms share 14 of 23 distinct attributes. CONCLUSION: The
      mapping of an institutional vocabulary to a structured controlled vocabulary
      requires that the mapping be performed at the level of terms, relationships, and
      attributes. The mapping process revealed the importance of standardization of
      local vocabulary subsets, standardization of attribute representation, and term
      granularity.

PMID- 8750392
TI  - A temporal analysis of QMR.
AB  - OBJECTIVE: To understand better the trade-offs of not incorporating explicit time
      in Quick Medical Reference (QMR), a diagnostic system in the domain of general
      internal medicine, along the dimensions of expressive power and diagnostic
      accuracy. DESIGN: The study was conducted in two phases. Phase I was a
      descriptive analysis of the temporal abstractions incorporated in QMR's terms.
      Phase II was a pseudo-prospective controlled experiment, measuring the effect of
      history and physical examination temporal content on the diagnostic accuracy of
      QMR. MEASUREMENTS: For each QMR finding that would fit our operational definition
      of temporal finding, several parameters describing the temporal nature of the
      finding were assessed, the most important ones being: temporal primitives, time
      units, temporal uncertainty, processes, and patterns. The history, physical
      examination, and initial laboratory results of 105 consecutive patients admitted
      to the Pittsburgh University Presbyterian Hospital were analyzed for temporal
      content and factors that could potentially influence diagnostic accuracy (these
      included: rareness of primary diagnosis, case length, uncertainty, spatial/causal
      information, and multiple diseases). RESULTS: 776 findings were identified as
      temporal. The authors developed an ontology describing the terms utilized by QMR
      developers to express temporal knowledge. The authors classified the temporal
      abstractions found in QMR in 116 temporal types, 11 temporal templates, and a
      temporal hierarchy. The odds of QMR's making a correct diagnosis in high temporal
      complexity cases is 0.7 the odds when the temporal complexity is lower, but this
      result is not statistically significant (95% confidence interval = 0.27-1.83).
      CONCLUSIONS: QMR contains extensive implicit time modeling. These results support
      the conclusion that the abstracted encoding of time in the medical knowledge of
      QMR does not induce a diagnostic performance penalty.

PMID- 8750393
TI  - Matching the level of evaluation to a project's stage of development.

PMID- 8750394
TI  - National Health Information Privacy Bill generates heat at SCAMC.

PMID- 8750395
TI  - Angiotensin II receptor antagonism: losartan - sites and mechanisms of action.
AB  - This review surveys the basic pharmacology of angiotensin II receptors and their
      antagonism; reviews the existing clinical experience with losartan, the first
      approved nonpeptide angiotensin II antagonist; suggests other possible clinical
      areas for angiotensin II receptor antagonism; and compares angiotensin-converting
      enzyme inhibition with angiotensin receptor antagonism.

PMID- 8750396
TI  - Effectiveness and safety of beclomethasone dipropionate, an intranasal
      corticosteroid, in the treatment of patients with allergic rhinitis.
AB  - There is an increasing trend toward topical intranasal corticosteroids as the
      preferred treatment for seasonal or perennial allergic rhinitis. This trend is
      based on the fact that the chronic, mucosal inflammation that accompanies
      allergic rhinitis responds to anti-inflammatory drugs such as topical
      corticosteroids. Intranasal corticosteroids, given before the natural antigen
      challenge, reverse preexisting inflammation and prevent nasal priming by
      antigens. One intranasal corticosteroid, beclomethasone dipropionate, has been
      available by prescription in the United States for more than a decade and has an
      established efficacy and safety profile in patients with allergic rhinitis.
      Beclomethasone dipropionate has become the standard to which other intranasal
      corticosteroid preparations are compared. In comparison with earlier
      corticosteroids (eg, hydrocortisone, prednisolone, dexamethasone, betamethasone)
      that caused adrenal suppression and other systemic adverse reactions, the actions
      of new corticosteroids, including beclomethasone dipropionate, are confined to
      the site of application. These drugs are also more rapidly metabolized, less
      irritating to the nasal mucosa, and have a longer duration of action. When given
      intranasally to relieve the sneezing, congestion, and rhinorrhea associated with
      seasonal and perennial allergic rhinitis, the newer corticosteroids have proved
      safe and effective. Despite the fact that topical nasal corticosteroids such as
      beclomethasone dipropionate are responsible for important improvements in the
      treatment of both allergic and nonallergic rhinitis as well as nasal polyposis
      and chronic sinusitis, these drugs may be underused, particularly in the
      pediatric population. Because of the concern of systemic side effects in younger
      children, less effective therapies are sometimes used.

PMID- 8750397
TI  - Drug interactions in transplantation.
AB  - Cyclosporine, tacrolimus, and mycophenolate are selective immunosuppressive
      agents commonly prescribed to prevent organ rejection. Drug interactions that
      increase their blood levels could expose transplant recipients to serious side
      effects, while drug interactions that decrease their blood levels may cause
      rejection episodes as a result of inadequate immunosuppression. Cyclosporine and
      tacrolimus are metabolized by the cytochrome P-450 enzyme system. Drugs that
      induce, inhibit, or compete for the same cytochrome P-450 enzyme could affect
      blood levels of these immunosuppressive agents.

PMID- 8750398
TI  - Risk of selected serious cardiac events among new users of antihistamines.
AB  - This retrospective cohort study examined the risk of selected serious cardiac
      events in new users of either astemizole or sedating antihistamines identified
      from the COMPASS Ohio Medicaid population of approximately 1 million active lives
      per year (1986-1992). (COMPASS is an automated claims database.) There were
      15,585 patients in the astemizole group and 30,105 in the sedating antihistamines
      group. Reports of ventricular arrhythmia or sudden death occurring within 30 days
      of the first antihistamine claim were identified from Medicaid claims. Medical
      records were obtained and reviewed by a clinician for validity of diagnoses.
      Records for patients without a full 30 days of follow-up were sought in the
      National Death Index. Death certificates were obtained for all patients who died
      within 30 days of the first antihistamine claim. Of 53 cases identified, 6 were
      in the astemizole group and 47 in the sedating antihistamines group. The relative
      risk for all selected cardiac events among astemizole users compared with
      sedating antihistamine users was 0.25 (95% confidence interval: 0.11 to 0.58),
      and this estimate did not change substantially when adjusted for age; sex; race;
      recent history of cardiovascular disease, arrhythmias, asthma/pulmonary disease,
      or malignant neoplasms; or concomitant prescription of other drugs. This study
      provided no evidence that astemizole users are at increased risk for cardiac
      events in the first month of use when compared with users of sedating
      antihistamines.

PMID- 8750399
TI  - Comparison of the onset and intensity of action of intramuscular meloxicam and
      oral meloxicam in patients with acute sciatica.
AB  - In this randomized, double-blind, double-dummy trial, 113 patients with acute
      sciatica were treated with a single 15-mg dose of meloxicam given intramuscularly
      (n = 54) or orally (n = 59). There was a significant improvement in induced pain
      (as measured by using the straight-leg-raising test) in both treatment groups at
      60 minutes (P < 0.005), and there was a significant difference in favor of the
      intramuscular formulation in terms of the time to maximum improvement of induced
      pain (P = 0.01). Changes in spontaneous pain were similar in both treatment
      groups and were significant versus baseline (P < 0.01) at 30 minutes after study
      drug administration. Global efficacy evaluations by both the patients and
      investigators confirmed that meloxicam 15 mg in an intramuscular or oral
      formulation was effective in relieving pain in patients with acute sciatica.
      Meloxicam was generally well tolerated, and the local tolerability of the
      intramuscular injection was found to be excellent on the basis of both clinical
      evaluation and assessment of creatine phosphokinase levels.

PMID- 8750400
TI  - Ondansetron for nausea and vomiting associated with moderately emetogenic cancer
      chemotherapy.
AB  - This multicenter, randomized, double-blind study compared the efficacy and
      tolerability of ondansetron 8 mg twice daily for 3 days with placebo in
      preventing nausea and vomiting in 81 patients receiving cyclophosphamide
      doxorubicin-based chemotherapy. The first dose of study drug was administered 30
      minutes before the initiation of chemotherapy. Patients received a rescue
      antiemetic if the investigator deemed it necessary or if the patient experienced
      more than two emetic episodes during the 3-day study. Sixty-one percent of
      patients treated with ondansetron compared with 6% of patients receiving placebo
      (P < 0.001) had no emetic episodes during the 3-day study. Among patients with at
      least one emetic episode, the mean time to emesis was 24 hours 18 minutes in the
      ondansetron group compared with 8 hours 1 minute in the placebo group (P <
      0.001). In the intent-to-treat analysis, 78% of patients in the ondansetron group
      and 29% of patients in the placebo group completed the study with no need for
      rescue therapy. Clinical laboratory and adverse-event profiles were similar
      between groups. The most common adverse event was headache, occurring in 23% of
      ondansetron patients and 24% of placebo patients. This study is the first double
      blind, placebo-controlled trial to demonstrate that ondansetron 8 mg twice daily
      is effective in the prevention of nausea and vomiting associated with
      cyclophosphamide-doxorubicin-based chemotherapy. The twice-daily regimen may
      encourage patient compliance and may be more cost-effective than regimens that
      need to be given three times daily.

PMID- 8750401
TI  - Onset of action of aqueous beclomethasone dipropionate nasal spray in seasonal
      allergic rhinitis.
AB  - Beclomethasone dipropionate nasal spray is widely used in the treatment of
      seasonal allergic rhinitis; however, the time of onset of action has not been
      determined. This study assessed the onset of action, level of relief, and
      efficacy of beclomethasone nasal spray in patients with seasonal allergic
      rhinitis. In a double-blind, randomized, placebo-controlled, parallel-group,
      multicenter, 7-day study, symptomatic patients were administered two inhalations
      of beclomethasone dipropionate (n = 80) or placebo (n = 81) into each nostril
      twice daily. Patients assessed the onset of action and level of relief at 6, 24,
      and 48 hours and at days 3 and 7. Investigators evaluated symptoms at days 0, 3,
      and 7 and response to therapy at days 3 and 7. The difference in the cumulative
      number of patients reporting relief of symptoms was statistically significant in
      favor of beclomethasone dipropionate by hour 24 (P = 0.05). Patients in the
      beclomethasone dipropionate group experienced a greater level of relief than
      patients receiving placebo at hour 24, and improvement increased over the 7-day
      study compared with a decrease in relief in the placebo group. Beclomethasone
      dipropionate was significantly more effective than placebo in reducing symptoms
      (P < or = 0.02), and patients in the beclomethasone dipropionate group showed a
      more favorable response to treatment than did patients in the placebo group (P <
      0.01). Adverse events were minor in both groups. Beclomethasone dipropionate
      nasal spray produced significant onset of relief of symptoms the first day of
      treatment; improvement was sustained and increased over the course of the study.

PMID- 8750402
TI  - Gastrointestinal blood loss induced by bromfenac sodium, aspirin, and placebo.
AB  - The effects of bromfenac sodium, aspirin, and placebo on gastrointestinal (GI)
      blood loss were compared. In a 22-day, randomized study, healthy men received
      treatment with either bromfenac sodium 300 mg/d, aspirin 3900 mg/d, or placebo
      for 10 days. On days 3 through 9 and days 20 through 22, all patients received
      placebo. Fecal blood was measured using the chromium 51-labeled red blood cell
      technique. Thirty-seven subjects entered the treatment period (13 in the aspirin
      group, 12 in the bromfenac sodium group, and 12 in the placebo group). The mean
      change in fecal blood loss during the treatment period compared with the baseline
      period was significantly greater in the aspirin group (8.00 +/- 4.17 mL/d) than
      in the bromfenac sodium group (1.63 +/- 1.01 mL/d). Blood loss in both the
      aspirin and bromfenac sodium groups was significantly greater than in the placebo
      group (-0.12 +/- 0.25 mL/d). It is concluded that bromfenac sodium 300 mg/d, a
      higher daily dose than the proposed daily dose, causes significantly less GI
      blood loss than aspirin 3900 mg/d.

PMID- 8750403
TI  - Effect of prostaglandin E1 on hepatic function after hepatectomy in patients with
      chronic liver disease.
AB  - We designed a clinical study to determine the effect of prostaglandin E1 (PGE1)
      on functional recovery of the liver after hepatectomy. Thirty-five patients with
      primary hepatic neoplasms accompanied by chronic liver disease were randomly
      divided into two groups: 13 patients received intravenous PGE1 at 0.06 micro g/kg
      per minute for 3 postoperative days (PGE1[+] group) and 22 patients did not
      (PGE1[-] group). All postoperative values of hepatic function tests were
      calculated as a ratio to each preoperative value. Significantly higher
      cholinesterase ratios were observed in the PGE1[+] group than in the PGE1[-]
      group 2 weeks postsurgery (P < 0.05). The alanine aminotransferase (ALT) ratios
      at 1 and 2 weeks postsurgery were 118% and 123% in the PGE1[+] group and 207% and
      175% in the PGE1[-] group, respectively. The ratio of the maximum postoperative
      ALT level was 503% in the PGE1[+] group and 792% in the PGE1[-] group (P < 0.05).
      We concluded that PGE1 would have the effect of conditioning the postoperative
      ALT elevation and cholinesterase deterioration and that the patient's
      postoperative course might be more favorable with the use of PGE1.

PMID- 8750404
TI  - Effect of cilazapril therapy on glucose and lipid metabolism in patients with
      hypertension.
AB  - The effects of long-term monotherapy with cilazapril, an angiotensin-converting
      enzyme inhibitor, on blood pressure, glucose tolerance, and serum lipid profiles
      were prospectively investigated in 66 patients with hypertension: 23 with normal
      glucose tolerance and 43 with glucose intolerance (including 9 patients with non
      insulin-dependent diabetes mellitus). The levels of plasma glucose, serum
      insulin, serum lipids, glycated hemoglobin A(lc) (Hb A(lc)), and fructosamine
      were determined before and during long-term (mean +/- SD, 26.2 +/- 1.2 weeks)
      therapy with cilazapril. A 75-g oral glucose tolerance test was performed before
      and during treatment. Significant reductions in both systolic and diastolic blood
      pressures in both patient groups were maintained during the study. Neither
      fasting nor post-glucose load venous plasma glucose levels were altered in either
      group of patients, and no patient with normal glucose tolerance developed
      diabetes mellitus during the study. There was no significant change in the
      insulinogenic index (delta serum insulin/delta venous plasma glucose at 30
      minutes post-glucose load) in either group, and glucose intolerance was slightly
      improved with significant reductions (P < 0.01) in Hb A(lc) and fructosamine in
      the patient group with impaired glucose tolerance. Serum total cholesterol (TC),
      low-density lipoprotein cholesterol, and triglyceride levels were significantly
      (P < 0.01) decreased and high-density lipoprotein cholesterol levels increased in
      patients with hypercholesterolemia (TC levels > or = 5.69 mmol/L). These results
      suggest that long-term cilazapril therapy may improve glucose and lipid
      metabolism in hypertensive patients with impaired glucose tolerance. Cilazapril
      also appears to be useful as an antihypertensive agent for hypertensive patients
      with either impaired glucose tolerance or hypercholesterolemia.

PMID- 8750405
TI  - Effects of lisinopril and bisoprolol on lipoprotein metabolism in patients with
      mild-to-moderate essential hypertension.
AB  - The short- and long-term effects of the angiotensin-converting enzyme inhibitor
      lisinopril and the cardioselective beta-blocker bisoprolol on serum lipids,
      lipoproteins, apolipoproteins, and lipoprotein(a) (Lp[a]) levels were
      investigated in patients with mild-to-moderate essential hypertension. Fifty-two
      patients completed the 12-month, randomized, multicenter trial. After
      administration of lisinopril (10 to 20 mg/d; n = 24) and bisoprolol (2.5 to 10
      mg/d; n = 28), systolic and diastolic blood pressures decreased significantly (P
      < 0.01) from baseline in both groups at 3, 6, and 12 months. The reduction in
      diastolic blood pressure was significantly (P < 0.05) greater in the lisinopril
      group than in the bisoprolol group only at 6 months. Heart rates dropped
      significantly in the bisoprolol group but not in the lisinopril group. No
      significant changes in lipids, lipoproteins, apolipoproteins, or Lp(a) levels
      were observed with either drug at 3, 6, or 12 months, and no significant
      differences were noted between the two drugs for these parameters. We conclude
      that lisinopril and bisoprolol are effective as antihypertensive drugs without
      adverse metabolic effects after short- and long-term treatment in patients with
      mild-to-moderate essential hypertension.

PMID- 8750406
TI  - Acid suppression by famotidine 20 mg twice daily or 40 mg twice daily in
      preventing relapse of endoscopic recurrence of erosive esophagitis.
AB  - Control of esophageal acid exposure is important in treating patients with
      gastroesophageal reflux disease (GERD). After complete healing of esophagitis,
      most patients will relapse within 6 months if left untreated. This multicenter,
      randomized, double-masked, placebo-controlled trial, conducted in the United
      States, examined whether two famotidine dosing regimens are effective in
      extending the time in remission for patients with moderate-to-severe erosive
      esophagitis. Of 172 patients enrolled, 31 received placebo, 69 received
      famotidine 20 mg twice daily (BID) , and 72 received famotidine 40 mg BID.
      Endoscopy was scheduled at baseline and at months 3 and 6. Patients assessed
      global heartburn and symptom relief at months 3 and 6 relative to the start of
      the study. Life table (Kaplan-Meier) relapse rates at 6 months were 22% (P <
      0.001 vs placebo) for famotidine 20 mg BID, 11% (P < 0.001 vs placebo) for
      famotidine 40 mg BID, and 62% for placebo. Compared with placebo, patients in the
      famotidine groups were significantly less likely to note global symptomatic
      deterioration, as measured by the distribution of global assessment responses.
      The incidence of clinical and laboratory adverse experiences was similar among
      treatment groups. For maintenance treatment of GERD, famotidine 20 mg BID and 40
      mg BID are more effective than placebo in extending the time in remission.

PMID- 8750407
TI  - Coprescribing of nonsteroidal anti-inflammatory drugs and cytoprotective and
      antiulcer drugs in Nova Scotia's senior population.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for the
      elderly and are commonly prescribed with cytoprotective or antiulcer drugs to
      prevent or treat gastrointestinal side effects. The objective of this study was
      to examine the utilization and drug costs of NSAIDs, and to examine
      coprescription of cytoprotective and antiulcer drugs with NSAIDs in the Nova
      Scotia population aged 65 years and older. The study used data from the Nova
      Scotia Seniors Pharmacare program database, which contains data on claims for all
      filled prescriptions to persons 65 years of age and older. We examined claims for
      the period April 1, 1993, to March 31, 1994. Aspirin accounted for the largest
      percentage of the total days supply of NSAIDs (25.2%), followed by diclofenac
      (18.8%) and naproxen (12.9%). Diclofenac accounted for the largest share of
      expenditures for NSAIDs (27.6%). Overall, 17.1% of the total days supply of
      NSAIDs were coprescribed with a cytoprotective or antiulcer drug. Histamine2
      blockers accounted for most coprescribed days supply (83.6%) followed by
      sucralfate (8.1%), misoprostol (4.5%), and omeprazole (2.3%). The appropriateness
      and cost-effectiveness of these coprescriptions must be examined.

PMID- 8750408
TI  - Retrospective drug utilization review and the behavior of Medicaid prescribers:
      an empirical marginal analysis.
AB  - The objectives of this study were to evaluate the effectiveness of drug
      utilization review (DUR) letter intervention on reducing the cost of medications
      under Medicaid. The target drugs in this study were six antiulcer agents
      prescribed for Alabama Medicaid recipients. The study group consisted of 100
      prescribers who received DUR intervention. A total of 3776 prescribers who did
      not receive DUR intervention served as the comparison group. Using an interrupted
      time series design, these 3876 prescribers were studied before and after the
      implementation of the DUR program. The study found that prescribers' behavior
      changed after the DUR letter were sent out, resulting in a reduction in the
      average marginal days of drug therapy and drug reimbursement per recipient. For
      the target drugs, there was an average savings of $112.73 per prescriber per
      month and a total of $136,370.82 savings per month for the Alabama Medicaid
      program.

PMID- 8750409
TI  - Measuring the impact of patient counseling in the outpatient pharmacy setting:
      the research design of the Kaiser Permanente/USC patient consultation study.
AB  - This article describes the research method used to measure the impact of three
      alternative models of patient counseling in the outpatient pharmacy setting. The
      study was conducted in pharmacies operated by the Southern California region
      Kaiser Permanente Medical Care Program. Both random assignment and large-scale
      geographic area research designs were used. The presentation of the research
      design includes discussions of data collection and patient sampling methods; the
      measurement of patient outcomes, including measures of health care costs and
      utilization, patient functional status, and quality of life. Demographic data are
      presented for the study population, including an analysis of potential biased
      selection of patients electing to participate in random assignment. Data are also
      presented documenting potential selection bias across geographically determined
      treatment groups in the geographic area design arm. Finally, the article presents
      the analysis plan for the study and discusses study limitations.

PMID- 8750410
TI  - Cost-effectiveness profiles with an expanding treatment population.
AB  - In trying to identify the therapeutic impact of a drug, clinical trials eliminate
      potentially confounding factors such as comorbidities, poor compliance and
      treatment errors in diagnosis, dosing, and drug interactions. Elimination of
      these variables means that attempts to use clinical data as the basis for
      predicting relative cost-effectiveness are fraught with difficulties. In this
      article a theoretical framework is proposed, which, for a single drug
      intervention, examines the relationship between assumed patterns of clinical
      effectiveness, costs of drug delivery, and the proportion of the prospective
      patient population being treated. Cost-effectiveness profiles are generated to
      represent both usual-treatment situations and situations where interventions to
      reduce misdiagnoses, adverse events, and noncompliance attempt to push clinical
      effectiveness to a maximum (given the existence of comorbidities). Without data
      describing effectiveness and cost profiles, and unless strict assumptions are
      made as to effectiveness and cost functions, profiles of cost-effectiveness
      cannot be predicted.

PMID- 8750411
TI  - Implicit memory.

PMID- 8750412
TI  - Recognition and selfhood.

PMID- 8750413
TI  - Memory and consciousness: an appreciation of Claparede and recognition et moiite.
AB  - Claparede's report of a case of amnesic syndrome is an early example of the
      cognitive neuropsychology paradigm, by which studies of brain-damaged patients
      are used to shed light on the nature of normal mental processes. The case
      illustrates the selective impairment of episodic memory, with procedural and
      semantic memory remaining intact. Moreover, the several demonstrations of
      preserved learning during amnesia comprise an early illustration of the
      dissociation between explicit and implicit memory. However, its greatest
      contemporary relevance is for theories of conscious recollection. Claparede
      underscored the role of the self, viewed as a knowledge structure, in conscious
      mental life, and he drew attention to three different modes of recognition:
      remembering, inferring, and knowing.

PMID- 8750414
TI  - Functional aspects of recollective experience in face recognition.
AB  - This article describes two experiments on awareness in recognition memory for
      novel faces. Two kinds of awareness, recollective experience and feelings of
      familiarity in the absence of recollective experience, were measured by
      "remember" and "know" responses. Experiment 1 showed that "remember" but not
      "know" responses were reduced by divided attention at study. Experiment 2 showed
      that massed versus spaced repetition of faces in the study list had opposite
      effects on "remember" and "know" responses. Massed repetition increased "know"
      responses and reduced "remember" responses. Spaced repetition increased
      "remember" responses and reduced "know" responses. The results of both
      experiments replicate previous findings from the verbal domain in the domain of
      face recognition, and hence they increase the ecological validity of this
      experimental approach to memory and awareness and the generality of its database.
      These findings are discussed from a rehearsal perspective on factors influencing
      the two states of awareness and in relation to the alternative "process
      dissociation" procedure.

PMID- 8750415
TI  - Affective discrimination and the implicit learning process.
AB  - A modified version of the mere exposure effect paradigm was utilized in an
      implicit artificial grammar learning task in an attempt to develop a procedure
      that would be more sensitive in assesing nonconscious learning processes than the
      methods currently utilized within the field of implicit learning. Subjects were
      presented with stimuli generated from a finite-state artificial grammar and then
      had to either (a) decide if novel items conformed to the rule structure of the
      grammar or (b) rate the degree to which they liked novel items. Because the
      latter task was the more indirect of the two procedures, subjects' ability to
      discriminate between well-formed and ill-formed items on this liking task was
      taken as a more sensitive piece of evidence of implicit learning, compared to
      performance on the rule conformity task. A subsequent test of subjects' explicit
      knowledge of the rules of the grammar showed that subjects do have some conscious
      knowledge of the artificial grammar, but subjects initially making liking
      decisions exhibited significantly less conscious rule knowledge than subjects
      initially making rule-conformity judgments. The findings are discussed in
      relation to the synergistic relationships among implicit perception, implicit
      memory, and implicit learning processes.

PMID- 8750416
TI  - A novel demonstration of enhanced memory associated with emotional arousal.
AB  - The relationship between emotional arousal and long-term memory is addressed in
      two experiments in which subjects viewed either a relatively emotionally neutral
      short story (presented as a brief slide show) or a closely matched but more
      emotionally arousing story and were tested for retention of the story 2 weeks
      later. Experiment 1 provides an essential replication of the results of Heuer and
      Reisberg (1990) and illustrates the common interpretive problem posed by the use
      of different stimuli (slides) in the neutral versus emotional stories. In
      Experiment 2, identical slides (and sequence) were used in both the neutral and
      arousal stories. Two different stories were created by varying the narration that
      accompanied each slide. In both experiments, subjects who viewed the arousal
      story both experienced a greater emotional reaction to the story than did the
      subjects who viewed the neutral story, and subsequently exhibited enhanced memory
      for the story. Subjects in Experiment 2 who viewed the arousal story also
      recalled more slides than did the subjects who viewed the neutral story. This
      effect was greatest for story phase 2, the phase in which the emotional slide
      narration occurred. Because this enhanced retention of the story slides cannot be
      explained by any differences in the slides themselves, the results provide new
      evidence to support the contention that emotional arousal influences long-term
      memory in normal human subjects.

PMID- 8750417
TI  - Measuring the relative magnitude of unconscious influences.
AB  - As an alternative to establishing awareness thresholds, stimulus contexts in
      which there were either greater conscious or greater unconscious influences were
      defined on the basis of performance on an exclusion task. Target words were
      presented for brief durations and each target word was followed immediately by
      its three-letter stem. Subjects were instructed to complete each stem with any
      word other than the target word. With this task, failures to exclude target words
      indicate greater unconscious influences, whereas successful exclusion indicates
      greater conscious influences. Conscious influences were dominant at long
      durations (e.g., 214 ms), but unconscious influences were dominant at short
      durations (e.g., 50 ms). Performance on the exclusion task successfully predicted
      both qualitative differences in Stroop priming and qualitative differences in
      recognition memory previously associated with the different effects of conscious
      and unconscious influences. Taken together, these results demonstrate that an
      exclusion task allows both unconscious and conscious influences to be defined in
      terms of significant deviations from baseline performance. As such, exclusion
      tasks provide a method for distinguishing conscious from unconscious influences
      that does not require establishing thresholds for null awareness.

PMID- 8750418
TI  - Auditory priming for nonverbal information: Implicit and explicit memory for
      environmental sounds.
AB  - Three experiments examined repetition priming for meaningful environmental sounds
      (e.g., clock ticking, tooth brushing, toilet flushing, etc.) in a sound stem
      identification paradigm using brief sound cues. Prior encoding of target sounds
      together with their associated names facilitated subsequent identification of
      sound stems relative to nonstudied controls. In contrast, prior exposure to the
      names alone in the absence of the environmental sounds did not prime subsequent
      sound stem identification performance at all (Experiments 1 and 3). Explicit and
      implicit memory were dissociated such that sound stem cued recall was higher
      following semantic than nonsemantic encoding, whereas sound priming was
      insensitive to manipulations of depth of encoding (Experiments 2 and 3). These
      results extend the findings of long-term repetition priming into the auditory
      nonverbal domain and suggest that priming for environmental sounds is mediated
      primarily by perceptual processes.

PMID- 8750419
TI  - Facilitation and interference in indirect/implicit memory tests and in the
      process dissociation paradigm: the letter insertion and the letter deletion
      tasks.
AB  - This paper introduced the letter insertion and letter deletion tasks. In these
      tasks participants are presented with letter strings and are instructed to insert
      or delete a letter to create a word. Experiment 1 demonstrated facilitation
      priming and established these tasks as sensitive indirect measures of memory.
      Experiments 2 and 3 demonstrated interference priming effects. In Experiment 4
      the process dissociation paradigm (Jacoby, 1991) was applied to investigate the
      contributions of automatic and consciously controlled processes to performance on
      the letter insertion task. In addition, performance in the exclusion condition
      demonstrated an interference effect caused by automatic retrieval. Potential
      applications for the letter insertion and letter deletion tasks are discussed.

PMID- 8750420
TI  - Dissociation of processes underlying spatial s-r compatibility: evidence for the
      independent influence of what and where.
AB  - The process-dissociation procedure was used to estimate the influence of spatial
      and form-based processing in the Simon task. Subjects made manual (left/right)
      responses to the direction of arrows (> or <) presented to the left or right of
      fixation. Manipulating the proportion of incongruent trials (e.g., a right
      pointing arrow presented to the left of fixation) affected both the size and
      direction of the Simon effect. To account for this pattern of data, we compared
      process estimates based on three possible relationships between spatial and form
      based processing: independence, redundancy, and exclusivity. The independence
      model provided the best account of the data. Most telling was that independent
      form-based estimates were superior at predicting observed performance on arrows
      presented at fixation and did so consistently across conditions (r's > .80). The
      results provide evidence that the form ("what") and spatial location ("where") of
      a single stimulus can have functionally independent effects on performance. They
      also indicate the existence of two kinds of automaticity--an associative
      ("implicit learning") component that reflects prior S-R mappings and a
      nonassociative component that reflects the correspondence between stimulus and
      response codes.

PMID- 8750421
TI  - Prevention of substance abuse????

PMID- 8750422
TI  - Sexual contact tracing outcome in adolescent chlamydial and gonococcal cervicitis
      cases.
AB  - BACKGROUND AND OBJECTIVE: Treatment of sex partners is an essential part of
      sexually transmitted diseases (STD) control. This study examined the efficacy of
      contact tracing via patient self-referral in gonococcal and chlamydial cervicitis
      cases among adolescents, compared with the effectiveness of provider-referral.
      STUDY DESIGN: Adolescent females with culture-proven chlamydial or gonococcal
      cervicitis were the study subjects. This cohort study was done in an urban non
      STD clinic setting. The subjects chose either provider-notification or self
      notification method to inform their sex partner(s) in 2 months preceding the
      interview date. RESULTS: Two hundred and sixty-five eligible subjects (91%
      African-American, 9% white) were identified. One hundred and ninety-eight sex
      contacts were reported by 165 (62%) cases; no contact was elicited in the
      remaining 100 (38%). The follow-up data revealed that 129/198 (66%) contacts were
      informed: 63 contacts by 61 index cases, 54 contacts of 47 cases by the case
      manager, 9 by both methods, and 3 by unspecified means. History of treatment was
      obtained in 54 contacts, including 37% (23/63) of patient-notified contacts and
      50% (27/54) of provider-notified contacts; these 54 contacts constituted 42% of
      informed contacts, or 27% of all named contacts. The mean number of sexual
      contacts treated per index case was 0.58 (27/47) for the provider-referral groups
      and 0.38 (23/61) for the self-referral groups. Successful contact tracing was
      documented in 19.3% (51/265) of all index cases, resulting in treatment of 54
      contacts. CONCLUSION: This study demonstrates the need for more effective partner
      treatment strategies in adolescent STD cases.

PMID- 8750423
TI  - Longitudinal stability and predictability of sexual perceptions, intentions, and
      behaviors among early adolescent African-Americans.
AB  - PURPOSE: To assess the stability and predictability of perceptions, intentions,
      and behaviors regarding intended sexual intercourse and condom use. METHODS: One
      hundred and nineteen African-American youth aged 9-15 years living in urban
      public housing provided information at baseline and 6 months later using a theory
      based and culturally- and developmentally-tailored instrument assessing
      perceptions, intentions, and sexual behaviors. RESULTS: Over the 6-month study
      interval, individual behaviors, intentions, and perceptions demonstrated
      considerable stability. Intentions regarding sexual intercourse in the next half
      year were predictive of subsequent coitus among the entire cohort and among the
      subset who were virgins at baseline. Youth who thought it likely that they would
      be sexually-active in the next 6 months were at significantly elevated risk of
      doing so, compared to youth who were uncertain or thought coitus unlikely.
      However, intentions regarding future coitus among the subset of youth who were
      sexually-experienced at baseline were not predictive of future coital behavior.
      CONCLUSIONS: These data suggest that social cognitive behavioral models that
      incorporate intentions and perceptions are appropriate as the theoretical basis
      for interventions targeting these young adolescents.

PMID- 8750424
TI  - Adolescents' perceptions of relative weight and self-reported weight-loss
      activities: analysis of 1990 YRBS (Youth Risk behavior Survey) national data.
AB  - PURPOSE: The purpose of the study was to examine, among public high school
      students across the United States, perceptions of relative weight-loss and its
      relationship to physical activity levels, time spent viewing television, and
      efforts to lose weight. METHODS: Self-reported data from the 1990 Youth Risk
      Behavior Survey (YRBS) were used to analyze these relationships. The YRBS was
      developed and administered by the Division of Adolescent and School Health
      (DASH), Centers for Disease Control and Prevention (CDC), to assess important
      health behaviors which contribute significantly to adverse health outcomes among
      American youth. A total of 10,870 black, Hispanic, and white respondents were
      included in this analysis. RESULTS: From this sample, 24.8% perceived themselves
      as being "too fat." Of that group, 76.4% were trying to lose weight. Females
      comprised 74.4% of those reporting that they were "too fat" and trying to lose
      weight. Gender differences in weight perceptions were significant (p < .001),
      with females (34.6%) being more likely than males (14.4%) to report being "too
      fat." Whites (26.0%) reported being "too fat" more often than did Hispanics
      (23.9%) and blacks (17.2%) (p < .001). Skipping meals and exercise were the most
      commonly reported weight loss strategies. Hispanics were most likely to skip
      meals, followed by whites and blacks. Whites were more likely than the other
      groups to use exercise as a means of losing weight. Adolescents who perceived
      themselves as "too fat" reported fewer days of strenuous activity (p < .001),
      fewer hours of strenuous exercise in physical education class (p < .001), and
      more hours spent viewing television on school days (p < .001) than others.
      CONCLUSIONS: One quarter of U.S. high school students perceive themselves as
      overweight; three-quarters of these students are trying to lose weight.
      Adolescents who perceive themselves as overweight are less physically active and
      spend more time viewing television than those who do not perceive themselves as
      overweight.

PMID- 8750425
TI  - Influences on adolescent eating behavior.
AB  - PURPOSE: The food consumption behavior of American adolescents often fails to
      meet dietary recommendations, indicating the need for investigation of the
      factors that influence this behavior. This study, guided by Bandura's Social
      Cognitive Theory, examined relationships between such behavior and other
      personal, environmental, and behavioral variables. METHODS: A paper-and-pencil
      instrument was administered to a sample of 242 high school students. "Pyramid,"
      fat, and sugar food scores were calculated to measure subjects' dietary diversity
      along with their consumption of fats and sugar/sweets. Statistical analyses were
      conducted to identify relationships between subjects' food scores and other study
      variables. RESULTS: Male and female subjects' pyramid scores were positively
      related (p < or = 0.05) to the number of meals they consumed daily. Some gender
      differences emerged in the data, as conformity to parents, snack consumption, and
      consumption of meals and snacks from home predicted males' Pyramid scores, while
      amount of physical exercise predicted pyramid scores of females. Both male and
      female subjects' fat and sugar scores were positively related (p < or = 0.05) to
      their consumption of meals and snacks from the school cafeteria and overall snack
      consumption and negatively related to their self-efficacy for making healthful
      food choices. Females' fat scores were further predicted by their consumption of
      fast food. CONCLUSIONS: Different aspects of adolescents' food consumption
      behavior may be influenced by different factors, which may vary between males and
      females. Therefore, nutrition and health professionals should tailor educational
      and treatment strategies according to both the gender of their patients and the
      specific desired dietary outcomes.

PMID- 8750426
TI  - Prevalence and correlates of psychopathology in pregnant adolescents.
AB  - PURPOSE: To investigate the prevalence and correlates of psychopathology, as
      measured by the Youth Self-Report Scale, in pregnant adolescents so that
      interventions during pregnancy may be tailored to treat the psychopathology and
      thereby improve maternal and child outcomes. METHODS: Scores on seven psychologic
      syndromes (withdrawn, delinquent, aggressive behaviors; anxiety/depression; and
      social, thought, and attention problems) were compared for groups of pregnant
      adolescents (n = 185), never pregnant teenagers (n = 126), and previously
      published normative samples of clinically referred (n = 518) and nonreferred (n =
      518) female adolescents using chi-square, Student's t-tests, analysis of
      covariance, or multiple logistic regression. Correlates of psychopathology were
      identified for the pregnant sample using odds ratios and 95% confidence limits.
      RESULTS: Pregnant adolescents exhibited less serious or lower rates of
      psychopathology than groups against which they were compared. Correlates of
      psychopathology included substance use during pregnancy, prior assault, maternal
      childbirth before age 18 years, ethnicity, > or = 3 sexual partners, and absence
      of a relationship with the baby's father. CONCLUSIONS: Although the prevalence of
      psychopathology was lower among pregnant patients, those who exhibit
      psychopathology are likely to engage in risky health behaviors that contribute to
      poor perinatal outcome.

PMID- 8750427
TI  - Glycemic control and transfer of health care among adolescents with insulin
      dependent diabetes mellitus.
AB  - PURPOSE: To describe glycemic control among older adolescents with insulin
      dependent diabetes mellitus (IDDM) as they move from pediatric to adult-focused
      health care. METHODS: Prospective cohort study conducted in a university medical
      center. Participants included 82 consecutive adolescents (50 males and 32
      females) with IDDM transferred from a pediatric to an adolescent/young adult
      diabetes clinic. Main outcome measures were the levels of total stable
      glycosylated hemoglobin (HbA1) obtained at each visit for up to one year before
      and after the transfer. RESULTS: The average age of transfer to the young adult
      clinic was 17.3 +/- 0.8 years. Mean age at onset of IDDM was 9.6 +/- 4.2 years
      (1.2 to 17.3) with duration of 7.7 +/- 3.9 years (0.7 to 16.1). Glycemic control
      remained unchanged following transfer (9.9% +/- 1.8 vs 10.2% +/- 1.9; t = 1.6; p
      = 0.125). Following transfer, both males and females maintained similar levels of
      glycemic control (9.8% +/- 1.7 and 10.7% +/- 1.8 respectively); although the
      difference between males and females was significant (t = -2.0; p = 0.048)
      following transfer, there was no difference in the degree of change by gender (t
      = -2.0; p = 0.8). In both pediatric and young adult clinics, there was no
      relationship between duration of IDDM (< 5 vs > or = 5 years) and HbA1.
      CONCLUSIONS: Transfer to an adult-focused diabetes program appears to have no
      negative impact on glycemic control.

PMID- 8750428
TI  - Factors influencing the intention to use condoms in Quebec sexually-inactive male
      adolescents.
AB  - PURPOSE: The purpose of this study was to determine whether attitudes and other
      variables would be associated with intention to use condoms in sexually-inactive
      male adolescents. METHODS: The survey was conducted from April to June 1989 on a
      sample of 879 sexually-inactive boys aged 12-19 years registered in secondary
      schools in Laval, Quebec. RESULTS: The major findings of the study were that: (1)
      information on condoms provided by peers was significantly associated with the
      intention to use condoms; (2) information provided by schools, while not
      significant in the final model, was positively associated with younger
      adolescents' intention to use condoms; and (3) sexually-inactive male adolescents
      in a less committed couple relationship had a greater intention to use condoms.
      CONCLUSIONS: The results of this study highlight the importance of peer
      instructors as a source of information on condoms, as well as that of teachers
      and health professionals from the school environment. Other channels of
      communication, however, need to be developed particularly for older sexually
      inactive adolescents who may be impervious to this latter source. The findings
      also underline the necessity to make sexually-inactive adolescents in stable
      couple relationships more aware of their potential vulnerability to STDs and AIDS
      should they commence sexual relations.

PMID- 8750429
TI  - Demographic and epidemiologic features of female adolescents in Turkey.
AB  - OBJECTIVES: To determine the average menarcheal age and menstrual cycle pattern,
      prevalence of dysmenorrhea, frequency of smoking, alcohol and drug use, sexual
      education level, and the gynecologic problems in female adolescents in Turkey.
      METHODS: A questionnaire consisting of 43 questions were given to 13,665 high
      school girls between the ages 13-18 years. RESULTS: The results showed that
      average menarcheal age was 13.28 +/- 1.09 years and 77.8% of the girls had
      menstrual cycles between 20-35 days; 10,688 (78.1%) of the girls complained about
      pain during their menstruation and 25.6% frequently missed school for this
      reason. That notwithstanding, only 0.4% of the adolescents with dysmenorrhea had
      sought medical consultation. Out of 13,665 girls, 19.7% smoked cigarettes, 14.9%
      used alcohol, and 0.63% used other drugs. Although 50.8% of the students believed
      that their knowledge about sexuality was adequate, on evaluating the results,
      this was not confirmed. Girlfriends were found to be the most important source of
      sexual knowledge. The study indicated that 88.8% of the girls wanted to have
      sexual education at schools and 60.5% of those preferred to take such a lecture
      together with boys. The study also revealed that 10.5% of the girls previously
      consulted a gynecologist and menstrual disorders (26.1%) and dysmenorrhea (23.4%)
      were the most common complaints. The results showed that 68.7% of the girls
      preferred a woman gynecologist and 66.3% wanted to be alone with the doctor
      during examination. CONCLUSION: We provided data about demographic and
      epidemiologic features of Turkish female adolescents.

PMID- 8750430
TI  - Cigarette smoking among junior and senior high school students in Japan.
AB  - PURPOSE: To estimate the smoking prevalence among junior and senior high school
      students in Japan. METHODS: We conducted a nationwide survey of adolescent
      smoking habits in 1990. Sample schools were selected by single random sampling.
      Self-administered anonymous questionnaires were sent to sample schools for all
      students to fill out. Seventy junior high schools and 33 senior high schools
      responded. A total of 57,189 students responded. RESULTS: The current smoking
      rate (the proportion of students who had smoked at least once during the previous
      month) was much higher among boys than girls. The current smoking rate among
      seventh graders was 4.0% for boys and 1.5% for girls, and it increased with age
      to reach 25.5% for boys and 4.9% for girls in the twelfth grade. The percentage
      of regular smokers in the seventh grade was less than 1% for both sexes, but it
      increased to 20.3% for boys and 2.2% for girls in twelfth grade. Among current
      smokers, the proportion of boys smoking 1-9 cigarettes per day decreased, and the
      proportion of boys smoking 10 or more cigarettes per day increased, as age
      increased. Most current smokers buy their cigarettes from cigarette vending
      machines or tobacconist shops. CONCLUSIONS: Since this survey reveals that
      smoking prevalence among students is not low even in junior high school, health
      education about smoking must start earlier and carry a greater emphasis within
      the curriculum. These results also indicate the importance of urging families to
      have greater concern for the smoking behavior of their children, of banning
      cigarette vending machines, and of preventing illegal sale of cigarettes to
      anyone under the age of 20 years.

PMID- 8750431
TI  - Ionic hydrogenation of 3-methoxy-14 alpha,15 alpha-methylenestra-1,3,5(10),8
      tetraen-17 alpha-ol: a correction.
AB  - 3-Methoxy-14 alpha,15 alpha-methylenestra-1,3,5(10),8-tetraen-17 alpha-ol on
      hydrogenation with triethylsilane/trifluoroacetic acid yielded 3-methoxy-14
      beta,15 beta-methylenestra-1,3,5(10)-trien-17 alpha-ol, not the 14 alpha,15 alpha
      methylene-9 beta product as previously described.

PMID- 8750432
TI  - The syntheses of 3-substituted perfluoroalkyl steroids.
AB  - The syntheses of three classes of C-3 perfluoroalkyl substituted steroids are
      described. They are the 3 beta-hydroxy-3 alpha-perfluoroalkylandrost-4-en-17-ones
      (5a-c), 3-perfluoroalkylandrosta-3,5-dien-3-ones (8a-c) and 3 beta-hydroxy-3
      alpha-perfluoroalkylandrost-5-en-17-ones (12a-c). Addition of a series of
      perfluoroalkylorganometallic reagents (RFLi; RF = C2F5, C3F7, or C4F9) to the 3
      position of silylated testosterone 2b afforded delta 4 perfluoroalkyl carbinols
      3. In Scheme 1, deprotection with HF and oxidation at the C-17 carbon with PCC
      produced delta 4 ketones 5. In Scheme 2 dehydration of 3 with 1,2
      phenylenephosphorochloridite and iodine afforded delta 3,5 dienes 6 which were
      deprotected and oxidized as above to the C-17 ketones 8. In Scheme 3
      isomerization of the double bond of 3 from the C-4 to the C-5 position using the
      allylic halogenation followed by treatment with lithium aluminum hydride led to
      the synthesis of the double bond isomer series 12. A new method for dehydration
      was developed. On average and within experimental error, 3 beta-hydroxy-3 alpha
      perfluoroalkylandrost-5-en-17 ones (12a-c) were better than the 3
      perfluoroalkylandrosta-3,5-dien-17-ones (8a-c) and 3 beta-hydroxy-3 alpha
      perfluoroalkylandrost-4-en-17-ones (5a-c) at inhibiting glucose-6-phosphate
      dehydrogenase.

PMID- 8750433
TI  - Chemical synthesis of 15 beta-hydroxytestosterone and its derivatives using a (4
      methoxyphenyl)methyl protecting group.
AB  - Reaction of 3 beta-hydroxyandrosta-5,15-dien-17-one with 4-methoxybenzyl alcohol
      followed by acetylation gave mainly 15 beta-[(4-methoxyphenyl)methoxy]-17
      oxoandrost-5-en-3 beta-yl acetate. This product was transformed by borohydride
      reduction and organosilyl derivatization into the orthogonally protected 17 beta
      (dimethylthexylsiloxy)-15 beta-[(4-methoxyphenyl)methoxy]androst-5-en-3 beta-yl
      acetate and 17 beta-(dimethylisopropylsiloxy)-15 beta-[4
      methoxyphenyl)methoxy]androst-5-en-3 beta-yl acetate. After deacetylation, these
      intermediates were submitted to Oppenauer oxidation and both yielded testosterone
      derivatives 17 beta-(dimethylthexylsiloxy)-15 beta-[(4
      methoxyphenyl)methoxy]androst-4- en-3-one and 17 beta-(dimethylisopropylsiloxy)
      15 beta-[(4-methoxyphenyl)- methoxy]androst-4-en-3-one. Removal of the (4
      methoxyphenyl)methyl group from position 15 by 2,3-dichloro-5,6-dicyano-1,4
      benzoquinone treatment gave the partially protected derivatives 17 beta
      (dimethylthexylsiloxy)-15 beta-hydroxyandrost-4-en-3-one and 17 beta
      (dimethylisopropylsiloxy)-15 beta-hydroxyandrost-4-en-3-one. After acidic
      deprotection, the dimethylthexylsilyl derivative yielded 15 beta
      hydroxytestosterone (15 beta,17 beta-dihydroxyandrost-4-en-3-one).
      Dimethylisopropylsilyl derivative was converted to the corresponding 15
      hemisuccinate and 15-hemiglutarate (17 beta-hydroxy-3-oxoandrost-4-en-15 beta-yl
      15-hemisuccinate and 15-hemiglutarate, respectively), which were designed as
      model haptens for immunoassay studies.

PMID- 8750434
TI  - Melatonin in the rat testis: evidence for local synthesis.
AB  - The vertebrate pineal gland rhythmically produces melatonin, a hormone involved
      in regulation of several physiological and behavioral processes. Melatonin is
      synthesized from serotonin essentially by two enzymatic steps involving N
      acetyltransferase (NAT) and hydroxyindole-O-methyltransferase activities. We have
      previously demonstrated the presence of melatonin binding sites in the rat
      testes, and an inhibitory effect of melatonin on testicular gonadotrophin
      stimulated androgen production. It is unknown whether these effects are mediated
      by melatonin synthesized locally or by melatonin from pineal origin. To assess
      the potential capacity of melatonin production by the testis, we used
      radiolabeled precursors to measure the activities of N-acetyltransferase and
      hydroxyindole-O-methyltransferase. The production of N-acetylserotonin was time
      dependent during over 10 min of incubation. Melatonin had a linear increase
      throughout the 30 min incubation period with S-adenosyl-L-[methyl-14C]methionine.
      Identities of melatonin and N-acetylserotonin were confirmed by thin-layer
      chromatography. The ability of the testis to synthesize melatonin during sexual
      maturation was also analyzed. When activity of NAT was expressed per mg of
      protein, the maximal activity was observed on day 40. In contrast, when activity
      of NAT is expressed by the testis, the amount of NAT increased to peak on day 40
      and remained elevated through day 70. We determined that both activities were
      predominantly localized in interstitial cells. NAT activity in seminiferous
      tubules was substantially decreased, representing 6.4% of NAT activity in
      interstitial cells. We concluded that rat testes are capable of synthesizing
      melatonin due to the presence of the enzymes necessary for the transformation of
      serotonin to melatonin.

PMID- 8750435
TI  - Distribution of hippocampal mineralocorticoid and glucocorticoid receptor mRNA in
      a glucocorticoid resistant nonhuman primate.
AB  - Glucocorticoids regulate the activity of the hypothalamic-pituitary-adrenal axis
      through both mineralocorticoid (MR) and glucocorticoid (GR) receptors in the
      hippocampus. In addition, glucocorticoids down-regulate hippocampal expression of
      MR and GR mRNA and protein, presumably decreasing their own effect. Marmosets are
      a New World primate characterized by extraordinarily high levels of circulating
      ACTH and cortisol. The relative glucocorticoid insensitivity of these animals to
      their massive levels of glucocorticoids was attributed to a decreased affinity of
      their GR for glucocorticoids, as well as a compromised ability of this receptor
      to transactivate glucocorticoid-responsive genes. The lack of mineralocorticoid
      excess, on the other hand, was attributed to a renal MR which responded poorly to
      cortisol, but normally to aldosterone. The purpose of this study was to examine
      MR and GR mRNA expression in the marmoset (Callithrix jacchus jacchus)
      hippocampus. Overall, steady state levels of both MR and GR mRNA were elevated in
      all of the hippocampal subfields of the marmoset, and this was obvious in rough
      comparisons with those of a typical glucocorticoid-sensitive Old World primate,
      the rhesus monkey (Macaca mulata). Notable were the extremely high levels of GR
      mRNA in the dentate gyrus and field CA3 of the marmoset. The GR mRNA density
      distribution of the marmoset also appeared to differ from that in the rhesus and
      from those previously reported in rats and humans. These findings suggest that
      there is a compensatory elevation of MR and GR mRNAs in the marmoset hippocampus,
      which appears to be the result of target tissue resistance to glucocorticoids and
      inappropriate down-regulation by the elevated, but ineffective, circulating
      cortisol.

PMID- 8750436
TI  - 15 beta-hydroxysteroids (part I). Steroids of the human perinatal period: the
      synthesis of 3 beta,15 beta, 17 alpha-trihydroxy-5-pregnen-20-one.
AB  - 15-Hydroxysteroids have long provided information about fetal well-being and
      fetal steroidogenesis. 3 beta,15 beta,-17 alpha-Trihydroxy-5-pregnen-20-one (1a)
      is a major 15 beta-hydroxylated metabolite unique to the human perinatal period.
      The synthesis of 3 beta, 15 beta, 17 alpha-trihydroxy-5-pregnen-20-one (1a) is
      reported here in the first of a series of publications on the chemical synthesis
      of 15 beta-hydroxylated steroids for use in the (a) development of new
      immunoassay techniques for application to newborn screening programs and fetal
      well-being; (b) development of new anti-androgenic drugs; and (c) study of
      androgen/estrogen interaction in late pregnancy. To this end, a method for the
      introduction of the 15 beta-hydroxy group onto the steroid nucleus was developed
      resulting in a nine-step stereoselective synthesis of 1a with an overall yield of
      26%. A high yielding selenation-dehydroselenation procedure was developed for the
      synthesis of 3 beta-hydroxy-5,15-androstadien-17-one (8) which avoided the
      previously reported Baeyer-Villiger rearrangement. The introduction of the 15
      beta-hydroxy group and the side chain was achieved by the addition of 2-lithio-2
      methyl-1,3-dithiane to give 20,20-trimethylenedithio-5,15-pregnadien-3 beta, 17
      beta-diol (9a) followed by its acid-catalyzed rearrangement to give 20,20
      trimethylenedithio-5, 16-pregnadien-3 beta,15 beta-diol (10a). Acetylation and
      cleavage of the dithioacetal gave 3 beta,15 beta-diacetoxy-5,16-pregnadien-20-one
      (11b) which was hydrogenated to give 3 beta,15 beta-diacetoxy-5-pregnen-20-one
      (12b). Reaction of the ketone (12b) with oxygen and then basic hydrolysis gave
      the desired product 1a.

PMID- 8750437
TI  - 15 beta-hydroxysteroids (part II). Steroids of the human perinatal period: the
      synthesis of 3 alpha,15 beta, 17 alpha-trihydroxy-5 beta-pregnan-20-one.
AB  - Steroids hydroxylated at C-15 have long provided useful information about the
      well-being of the fetus and feto-placental unit in human pregnancy. In an attempt
      to develop a new and reliable immunoassay method for use in newborn screening
      programs for congenital adrenal hyperplasia, we report the chemical synthesis of
      3 alpha,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (2) from 3 alpha
      hydroxy-5 beta-androstan-17-one (4) in 9 steps. In brief, 3 alpha-hydroxy-5 beta
      androst-15-en-17-one (6), was obtained from 4 by phenylselenation yielding 3
      alpha-hydroxy-16 alpha-phenylseleno-5 beta- androstan-17-one (5a) which on
      dehydroselenation gave 6. Introduction of the 15 beta-hydroxy group and the side
      chain was achieved by the addition of 2-lithio-2-methyl-1,3- dithiane followed by
      an acid-catalyzed rearrangement to give 20,20-trimethylenedithio-5 beta-pregn-16
      en- 3 alpha,15 beta-diol (8a). Acetylation then cleavage of the dithioacetal gave
      3 alpha,15 beta-diacetoxy-5 beta-pregn-16-en- 20-one (9) which on hydrogenation
      gave 3 alpha,15 beta-diacetoxy-5 beta-pregnan-20-one (10). Reaction of base and
      oxygenation of 10 gave a mixture of products which on basic hydrolysis gave 3
      alpha,15 beta,17 alpha-trihydroxy-5 beta- pregnan-20-one (2) in an overall yield
      of 8.8%.

PMID- 8750438
TI  - Preparation and properties of 3-(O-(2-carboxyethyl)oxime derivatives of steroid
      hormones.
AB  - Mixtures of 3E and 3Z isomers of 3-(O-(2-carboxyethyl)oxime (CEO) derivatives of
      testosterone and 17 alpha-methyltestosterone were prepared by reaction with (O-(2
      carboxyethyl))hydroxylamine. These isomers were separated after conversion into
      methyl esters, and mild alkaline hydrolysis recovered pure E/Z-isomers of 3-CEO
      derivatives of testosterone and 17 alpha-methyltestosterone. By the same method,
      after oximation, methylation, and separation, (20R)-20-hydroxypregn-4-en-3-one
      gave (3E,2OR)-20-hydroxypregn-4-en-3-one 3(O-(2-carboxyethyl)oxime and (3Z,20R)
      20-hydroxypregn-4-en-3-one 3-(O-(2-carboxyethyl))oxime methyl esters. The
      oxidation and subsequent hydrolysis of these compounds produced 3E and 3Z isomers
      of the 3-CEO derivative of progesterone. Pure E/Z-isomers of 3-CEO derivatives
      are designed for the development of immunoanalytical systems, which make use of
      the bridge heterology based on the geometric isomerism.

PMID- 8750439
TI  - Steroid transformations in pregnant mares: metabolism of exogenous progestins and
      unusual metabolic activity in vivo and in vitro.
AB  - The mare possesses unique steroid hormone metabolic activity during pregnancy in
      that peripheral 4-pregnene-3,20-dione (progesterone; P4) is undetectable by 220
      days gestation. This study examines in vivo metabolism of progestins by the
      pregnant mare and in vitro metabolic activity of maternal and fetal tissues.
      Pregnant mares (n = 3) received intravenous infusions of 3 beta-hydroxy-5-pregnen
      20-one (pregnenolone; P5), P4, 5 alpha-pregnane-3,20-dione (5 alpha-DHP), 3 beta
      hydroxy-5 alpha-pregnan-20-one (3 beta-5 alpha), deuterium labeled (D4)-P5, D4-3
      beta-5 alpha and vehicle. Anestrous mares (n = 2) were infused with P5, P4, and
      vehicle. Also, placenta, endometrium, fetal gonad, maternal and fetal liver, and
      adrenal from 4 animals were incubated in D4-P5, D4-5 alpha-DHP, or D4-3 beta-5
      alpha. Pregnant mares (in vivo) converted infused P5 predominantly to 5-pregnene
      3 beta,20 beta-diol (P5-beta beta), 5 alpha-DHP, 20 alpha-hydroxy-5 alpha-pregnan
      3-one (20 alpha-5 alpha), and 3 beta-5 alpha while only minor concentrations of
      P4 were detected. Infused P4 was converted primarily to 5 alpha-DHP and 20 alpha
      hydroxypregnanes and when 5 alpha-DHP served as a substrate, other 5 alpha
      pregnanes were formed. Infused 3 beta-5 alpha was either reduced to beta alpha
      diol or oxidized to 5 alpha-DHP. Regardless of treatment, anestrous mares were
      incapable of producing any 20 alpha-hydroxypregnanes but could convert P5 to P5
      beta beta and P4 in quantities similar to that of pregnant mares. In vitro,
      placenta converted D4-P5 to D4-P4 while D4-3 beta-5 alpha was oxidized to D4-5
      alpha-DHP. Endometrium converted substrate primarily to D4-20 alpha
      hydroxypregnanes. Both maternal and fetal liver produced D4-20 beta-hydroxy
      compounds regardless of substrate. Maternal and fetal adrenal were capable of
      conversion of D4-P5 to D4-P4 while fetal gonad did not perform any significant
      metabolism of substrate, though it produced P5. These data explain the absence of
      P4 and presence of other progestin metabolites in maternal circulation during mid
      and late pregnancy. Pregnenolone can be 5 alpha-reduced to 3 beta-5 alpha, and 3
      beta-5 alpha could be 3-oxidized to 5 alpha-DHP. It is 5 alpha-DHP that may serve
      as substrate for other 5 alpha-pregnanes.

PMID- 8750440
TI  - Effect of intraarticular pressure on patellar position. Computed tomography study
      in cadaveric specimens.
AB  - RATIONALE AND OBJECTIVES: The purpose of the study was to evaluate the effect of
      articular fluid distention on patellar position at different degrees of knee
      angulation. METHODS: Patellar position in 10 cadaveric knee specimens was
      determined with 30, 100, and 200 mm Hg joint distention at 45, 20, and 5 degrees
      of knee flexion using computed tomography. Patellar tilting and lateromedial and
      anteroposterior displacement of the patellar position were analyzed. RESULTS:
      Lateral tilting increased with greater articular distention and decreasing knee
      flexion. At 5 degrees of flexion and 200 mm Hg of distention, change in lateral
      tilting ranged from -7 to +5 degrees. At 45 degrees of flexion and increased
      distention, the patellar shift ranged from 6 mm medialization to 1 mm
      lateralization for 200 mm Hg, but the patellar position was more variable at 5
      degrees of flexion with increasing intraarticular pressure (range 7 mm
      medialization to 8 mm lateralization). With increasing articular pressure the
      patellae were increasingly displaced anteriorly with the most pressure-dependent
      changes at 45 and 20 degrees of knee flexion. CONCLUSIONS: Fluid distentions of
      the knee joint have unpredictable and varying effects on the patellar position
      and vary considerably among persons. When judging patellar position during
      arthroscopy and in patients with large joint effusions, the arthroscopist and
      radiologist should be aware of these effects.

PMID- 8750441
TI  - Color Doppler ultrasound and spectral analysis of tumor vessels in the
      differential diagnosis of solid breast masses.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the
      usefulness of color Doppler and spectral analysis of specific tumor vessels in
      the differentiation of benign from malignant breast masses. METHODS: Forty-eight
      patients with solid breast masses were evaluated with color Doppler ultrasound
      prospectively. When tumor vessels were visualized, spectral analysis was
      performed and peak systolic and end diastolic Doppler frequency shifts were
      recorded. Histology was obtained in all but two cases. RESULTS: In 28 out of 29
      malignant lesions tumor vessels were visualized. Thirteen of 19 benign lesions
      showed no demonstrable flow. The peak systolic Doppler frequency shifts recorded
      over the vessels of the malignant breast masses were significantly higher than
      those of the benign breast masses (P < 0.01). CONCLUSIONS: In our preliminary
      series, spectral Doppler analysis of tumor vessels shows promise in
      differentiating benign from malignant breast masses.

PMID- 8750442
TI  - Ultrasound demonstration of gallbladder wall thickening as a method to
      differentiate cirrhotic ascites from other ascites.
AB  - RATIONALE AND OBJECTIVES: Gallbladder wall thickness was measured by ultrasound
      in 16 patients with ascites caused by liver cirrhosis and in 16 noncirrhotic
      patients with ascites. This study was performed to evaluate if gallbladder wall
      thickening could differentiate cirrhotic ascites from ascites due to other
      causes. METHODS: Gallbladder thickness was measured by duplex ultrasound in 16
      cirrhotic patients with ascites and in 16 noncirrhotic patients with ascites.
      Measurements of portal vein flow and serum albumin also were performed. RESULTS:
      Gallbladder wall thickness was 0.76 +/- 0.21 cm in cirrhotic patients and 0.24 +/
      0.09 in noncirrhotic patients (P < 0.001, Student's t test for unpaired data).
      Gallbladder wall thickening was significantly more frequent in patients with
      cirrhotic ascites than in patients with noncirrhotic ascites (P < 0.001, chi
      square test). CONCLUSIONS: The authors feel that the ultrasound finding of
      gallbladder wall thickening in patients with ascites is highly predictive of
      liver cirrhosis diagnosis.

PMID- 8750443
TI  - The prostate: decreasing cost-effectiveness of biopsy with advancing age.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to determine the cost
      effectiveness of prostate biopsy at different excess prostate-specific antigen
      (PSA) levels as a function of age. METHODS: Medical decision analysis was
      performed with standard software (SMLTREE) to determine marginal effectiveness in
      quality adjusted life years (QALYs) and marginal cost-effectiveness in dollars
      per QALY of immediate prostate biopsy at different excess PSA levels between 0
      ng/mL and 20 ng/mL. The probability of clinically significant cancer with a
      positive biopsy (pD+Bx+) was assumed to decrease with age from 1.0 at age 50 to
      0.2 at age 70. Costs were based on charges at our hospital and were considered
      over a 2-year time frame. RESULTS: With our base case assumptions there was a
      decrease in QALYs and an increase in costs doing an immediate prostate biopsy at
      all excess PSA levels between 0 ng/mL and 20 ng/mL, compared with not biopsying
      the prostate at > or = 70 years. Doubling pD+Bx+ from 0.2 to 0.4 in the 70-and
      older age group resulted in a small increase in QALYs in biopsying the prostate
      at excess PSA levels between 0 ng/mL and 20 ng/mL. However, the marginal cost
      effectiveness of prostate biopsy was very high, ranging from $275,000/QALY
      biopsying at an excess PSA level of 0 ng/mL to $68,000/QALY biopsying at an
      excess PSA level of 20 ng/mL. This compared with it being more effective and less
      costly to biopsy at all excess PSA levels > or = 0 ng/mL in 50-year old patients.
      CONCLUSION: Immediate prostate biopsy is not cost-effective and can be
      detrimental in patients > or = 70 years of age at all excess PSA levels between 0
      ng/mL and 20 ng/mL.

PMID- 8750444
TI  - Application of pharmacokinetics to computed tomography: injection rates and
      schemes: mono-, bi-, or multiphasic?
AB  - OBJECTIVE: The objective of the current study was to test whether optimization of
      dose regimens for detecting focal liver lesions by computed tomography is
      possible by using the available time-density data of former studies published in
      the literature and a computer program so that the number of further clinical
      tests with the exclusive objective of optimizing injection schemes could be
      reduced. METHODS: Computed tomography enhancement data of the aorta and/or the
      liver obtained after injecting a conventional ionic and a nonionic contrast agent
      were used to calculate pharmacokinetic parameters and to simulate the time course
      of enhancement for a variety of different infusion regimens modifying contrast
      medium strength, dose, and injection rate. The study consisted of two parts. In
      the first part, mean relative enhancement curves of the aorta and of liver
      parenchyma (0 to 300 sec) using meglumine diatrizoate (306 mg iodine per mL, 300
      mg iodine per kg) were taken from the literature and their values were
      approximated using the computer program TOPFIT. In the second part, equivalent
      data for iohexol including a total of three strengths (240, 300, and 350 mg
      iodine per kg) and doses from 30 to 45 grams of iodine were used. "Validation" of
      the simulation method was obtained, first by comparing measured and calculated
      maximum intensities and times to reach maximum and, second, by using one
      injection scheme for the simulation of a second and comparing the results with
      actually measured data. RESULTS: The computer program TOPFIT allowed for
      excellent curve fitting of the measured density values. The data obtained in the
      first part of the study showed that after a dose of 300 mg I/kg and a rate of 2
      mL/sec maximal enhancement is achieved in the aorta after 30 seconds
      (approximately 100 HU) and in the liver after 50 seconds (approximately 30 HU).
      The higher the dose and the rate of infusion were, the higher was the
      enhancement. The difference in density between aorta and liver was proportional
      to the infusion rate approaching asymptotically approximately 90 HU at 8 mL/sec
      for a dose of 300 mg I/kg. Bi- or triphasic infusion schemes did not improve
      differences in enhancement. The curve fitting obtained in the second part of the
      study also confirmed the results reported in the literature. A "crossover"
      prediction of data was possible within the range of interindividual variations of
      pharmacokinetic parameters and thus validated the chosen approach of computer
      simulation. Furthermore, data sets selected randomly out of the simulation
      results could be used--within the limits of interindividual variability--to
      predict data determined in other clinical trials. CONCLUSION: The computer
      program TOPFIT appears useful for the optimization of time--density profiles in
      computed tomography. The number of further clinical studies with the objective of
      optimization could therefore possibly be reduced.

PMID- 8750445
TI  - Prospective optimization of patient selection for emergency cranial computed
      tomography: univariate and multivariate analyses.
AB  - RATIONALE AND OBJECTIVES: To determine if the clinical variables that are
      important for selecting patients for emergency cranial computed tomography (CT)
      are population dependent. METHODS: Prior to obtaining scans, physicians working
      in an emergency department in a level II trauma center completed a form
      describing the indication for the CT examination. These data were matched to the
      CT scan results and analyzed statistically using univariate and multivariate
      methods. These results were compared with a prior study at a level I trauma
      center. RESULTS: Of 551 patients having cranial CT, neurologic examination was
      positive in 340 and CT scan was positive in 122. The neurologic examination
      correlated strongly with the results of the CT scan (P < 0.00001). In this
      patient population, the most important clinical predictors of 17 abnormal CT
      scans from the 211 patients without positive neurologic examinations were seizure
      and a history of neoplasm. These high-yield variables differ from our prior
      retrospective study in which intoxication and amnesia were the important
      predictors in patients with negative examinations. The difference in predictors
      between the populations most likely results from different prevalences of trauma
      and ischemic disease. CONCLUSIONS: Abnormal neurologic examination is the most
      important criterion available to select patients for emergency cranial CT. Other
      variables (eg, seizure, amnesia, intoxication, and history of neoplasm) that help
      select patients without neurologic findings appear to be population dependent.

PMID- 8750446
TI  - Take-home informed consent for intravenous contrast media: do patients learn
      more?
AB  - RATIONALE AND OBJECTIVES: In 1978, Morrow et al published the results of a simple
      technique for raising radiation oncology patients' levels of awareness about
      medical options. They reported that providing written information at least 24
      hours in advance was an effective tool for increasing the baseline knowledge in
      this patient group. However, Morrow's cohort consisted exclusively of cancer
      patients receiving radiation therapy. The authors of this article are concerned
      with whether the encouraging results reported by Morrow are reproducible when
      applied to patients awaiting invasive radiologic procedures. METHODS: One hundred
      sixty consecutive outpatients awaiting contrast were block randomized into one of
      eight groups based on age, sex, and previous contrast exposure. For each group,
      half were given their consent form at least 24 hours prior, and the other half at
      the time of their procedure. All patients were tested at the time of their
      procedure to evaluate knowledge retention. RESULTS: Comparison between the two
      study groups showed no overall statistically significant differences either in
      knowledge (experimental group 4.7 +/- 1.32 versus 4.38 +/- 1.30 control group) or
      level of satisfaction. Additionally, individuals experienced with contrast failed
      to outperform those who had never previously been given contrast. There is no
      significant difference in the performance between the two sexes regardless of
      group. CONCLUSIONS: The providing of information 24 to 72 hours in advance of an
      invasive procedure does not have a beneficial effect over just providing the same
      information at the time of the study.

PMID- 8750447
TI  - Correlation of ultrasound bone velocity with dual-energy X-ray bone
      absorptiometry in rat bone specimens.
AB  - RATIONALE AND OBJECTIVES: To investigate bone mass measurements by ultrasound
      bond velocity (UBV) in bone specimens obtained from experimental animals.
      METHODS: The authors made UBV measurements in 40 femurs and tibias dissected from
      Sprague-Dawley rats (14 weeks-old, mean weight 290 g) and compared them with bone
      densitometric measurements made on the same material using dual-energy x-ray
      absorptiometry (DXA). RESULTS: The coefficient of variation for UBV measurements,
      based on values obtained in five femurs and five tibias at different times, was
      0.2% and 0.3% respectively. Regression studies yielded a correlation between UBV
      and bone mineral density in femur of r = 0.87 (P < 0.0001) and with bone mineral
      content of r = 0.65 (P < 0.0001); in the tibia similar levels of significance
      were obtained. The correlation between femur weight and UBV was r = 0.51 (P <
      0.0005) and with bone mineral content it was r = 0.79 (P < 0.0001). Partial
      correlation between UBV and femur bone mineral density, with respect to bone
      weight, was r = 0.68 (P < 0.001), and with femur bone mineral content was r =
      0.71 (P < 0.0001). In the tibia measurements were similarly significant.
      CONCLUSIONS: Measurements of bone mass made with ultrasound transmission velocity
      are precise correlate well with DXA measurements.

PMID- 8750448
TI  - An ecological view of psychological trauma and trauma recovery.
AB  - This paper presents an ecological view of psychological trauma and trauma
      recovery. Individual differences in posttraumatic response and recovery are the
      result of complex interactions among person, event, and environmental factors.
      These interactions define the interrelationship of individual and community and
      together may foster or impede individual recovery. The ecological model proposes
      a multidimensional definition of trauma recovery and suggests that the efficacy
      of trauma-focused interventions depends on the degree to which they enhance the
      person-community relationship and achieve "ecological fit" within individually
      varied recovery contexts. In attending to the social, cultural and political
      context of victimization and acknowledging that survivors of traumatic
      experiences may recover without benefit of clinical intervention, the model
      highlights the phenomenon of resiliency, and the relevance of community
      intervention efforts.

PMID- 8750449
TI  - Cumulative trauma: the impact of child sexual abuse, adult sexual assault, and
      spouse abuse.
AB  - The present study investigated the relationship between trauma symptoms and a
      history of child sexual abuse, adult sexual assault, and physical abuse by a
      partner as an adult. While there has been some research examining the correlation
      between individual victimization experiences and traumatic stress, the cumulative
      impact of multiple victimization experiences has not been addressed. Subjects
      were recruited from psychological clinics and community advocacy agencies.
      Additionally, a nonclinical undergraduate student sample was evaluated. The
      results of this study indicate not only that victimization and revictimization
      experiences are frequent, but also that the level of trauma specific symptoms are
      significantly related to the number of different types of reported victimization
      experiences. The research and clinical implications of these findings are
      discussed.

PMID- 8750450
TI  - Stress debriefing and patterns of recovery following a natural disaster.
AB  - Stress debriefing has been used extensively following traumatic events; however,
      there is little evidence of its effectiveness. This paper reports the effects of
      stress debriefing on the rate of recovery of 195 helpers (e.g., emergency service
      personnel and disaster workers) following an earthquake in Newcastle, Australia
      (62 debriefed helpers and 133 who were not debriefed). Post-trauma stress
      reactions (Impact of Event Scale) and general psychological morbidity (General
      Health Questionnaire: GHQ-12) were assessed on four occasions over the first 2
      years postearthquake. There was no evidence of an improved rate of recovery among
      those helpers who were debriefed, even when level of exposure and helping-related
      stress were taken into account. More rigorous investigation of the effectiveness
      of stress debriefing and its role in posttrauma recovery is urgently required.

PMID- 8750451
TI  - Posttraumatic stress reactions in volunteer firefighters.
AB  - Volunteer firefighters in NSW were surveyed for experiences of posttraumatic
      stress. Firefighters were asked to describe their experiences of stress and
      indices were obtained of psychological disturbance. Findings indicated that most
      firefighters felt that their safety had been threatened. One-quarter of
      firefighters indicated that they experienced significant levels of posttraumatic
      stress, although many respondents attributed their stress to personal events.
      Posttraumatic stress was associated with multiple and recent critical incidents.
      Findings are discussed in terms of etiological factors of posttraumatic stress
      and the need for appropriate intervention.

PMID- 8750452
TI  - Stress responses of emergency services personnel to the Loma Prieta earthquake
      Interstate 880 freeway collapse and control traumatic incidents.
AB  - A three-group quasi-experimental design contrasted the responses of rescue
      workers to the 1989 Loma Prieta earthquake Interstate 880 freeway collapse (n =
      198) with responses to critical incident exposure of Bay Area Controls (n = 140)
      and San Diego Controls (n = 101). The three groups were strikingly similar with
      respect to demographics and years of emergency service. The I-880 group reported
      higher exposure, greater immediate threat appraisal, and more sick days. The
      three groups did not differ on current symptoms. For the sample as a whole
      EMT/Paramedics reported higher peritraumatic dissociation compared with Police.
      EMT/Paramedics and California road workers reported higher symptoms compared with
      Police and Fire personnel. Nine percent of the sample were characterized as
      having symptom levels typical of psychiatric outpatients. Compared with lower
      distress responders, those with greater distress reported greater exposure,
      greater peritraumatic emotional distress, greater peritraumatic dissociation,
      greater perceived threat, and less preparation for the critical incident.

PMID- 8750453
TI  - Coping with Ottoman Turkish Genocide: an exploration of the experience of
      Armenian survivors.
AB  - This study explored the experiences of the survivors of the Ottoman-Turkish
      Genocide of the Armenians (1915-1923). Coping strategies, communication patterns
      and the impact of continuing Turkish denial of the events were the specific
      research areas. Semi-structured interviews were administered to 40 Genocide
      survivors, residing at two Armenian homes for older adults in the mid-Atlantic
      United States. Destruction of life, physical harm, deportation, pillaging, and
      loss of status were identified by respondents as stressors experienced. Religion,
      family, work, denial, and resignation were identified as coping methods and
      sources of survival. Most respondents had not discussed their experiences with
      others. When asked about their reactions to the Turkish denial, respondents
      expressed a range of negative affect, including resentment, hatred, and rage.
      When asked about sources of pride in their lives, respondents cited
      accomplishments such as surviving the Genocide, surviving as Armenians and
      procreating. The social, developmental, and psychiatric implications of the
      findings were discussed.

PMID- 8750454
TI  - Elimination of posttraumatic symptomatology by relaxation and visual-kinesthetic
      dissociation.
AB  - Five patients suffering from posttraumatic stress disorder and experiencing
      persistent intrusive imagery were treated with two sessions of relaxation
      training followed by two sessions of the visual-kinesthetic dissociation
      technique. Outcome was monitored using a multiple baseline design. Despite the
      briefness of the intervention, three of the patients showed an almost complete
      reduction in the frequency of their intrusive images and substantial changes on
      other measures of psychopathology. One patient showed partial improvement and one
      patient showed no improvement at all.

PMID- 8750455
TI  - The utility of the SCL-90-R for the diagnosis of war-zone related posttraumatic
      stress disorder.
AB  - A scale for assessing war-zone-related posttraumatic stress disorder (WZ-PTSD
      scale) was derived from the Symptom Checklist-90-R by identifying items that best
      discriminated Vietnam theater veterans with and without PTSD (N = 202). The 25
      item WZ-PTSD scale had excellent internal consistency, and signal detection
      analyses revealed that its diagnostic utility was comparable to or exceeded that
      of several established PTSD scales and measures of global distress. In a cross
      validation sample (N = 99), the diagnostic utility of the WZ-PTSD scale was
      stable, whereas other PTSD scales performed more poorly. The WZ-PTSD scale
      appears to be a valuable new measure of PTSD that can be particularly useful in
      archival data sets or in any situation where other PTSD measures are not
      available.

PMID- 8750456
TI  - Periodic limb movements of sleep in combat veterans with posttraumatic stress
      disorder.
AB  - Twenty-five veterans suffering from combat-related posttraumatic stress disorder
      were studied for 1-4 nights with all-night polysomnography. All subjects had
      sleep complaints. Analysis reveals that nineteen (76%) of the patients were found
      to have clinically significant periodic limb movements of sleep (PLMs) by the
      second night of study. PLMs are associated with sleep complaints in normals. For
      this reason the common assumption that sleep complaints in posttraumatic stress
      disorder are related only to the psychiatric disorder itself are challenged.

PMID- 8750457
TI  - Subjective versus objective sleep in Vietnam combat veterans hospitalized for
      PTSD.
AB  - Twenty-five Vietnam combat veterans with chronic severe posttraumatic stress
      disorder (PTSD) completed a sleep self-report questionnaire on admission to an
      inpatient treatment program. Between 1 and 2 months later each spent 3 or more
      nights in the sleep laboratory. When self-report and laboratory findings were
      compared, significant relationships were observed between sleep schedule items
      such as time-to-bed/time-out-of-bed and polysomnographic measures of sleep. In
      contrast, global ratings of sleep quality were generally unrelated to
      polysomnographic measures. These findings may have implications for survey
      research assessing sleep quality in traumatized populations.

PMID- 8750458
TI  - Quality of Life in Clinical Cancer Trials. Introduction.

PMID- 8750459
TI  - Trial-related quality of life: using quality-of-life assessment to distinguish
      among cancer therapies.
AB  - Issues in selecting quality-of-life (QOL) measures that are best suited to
      assessing differences among treatments in cancer clinical trials, as well as
      challenges to interpreting QOL outcome data, are discussed. When used in the
      context of randomized trials of cancer therapies, QOL assessments must provide an
      answer to the question, "Did the treatments differentially affect patient well
      being?" In order to detect differences in treatment efficacy against a background
      of great similarity, the broad concept of QOL needs to be refined to reflect
      "trial-related QOL." In many cases, this will entail emphasis on actual patient
      experience of symptoms and functional changes, as opposed to emphasis solely on
      evaluation and satisfaction. A model is proposed to identify cognitive,
      emotional, and sociocultural factors that influence a patient's QOL evaluation
      and that need to be considered in understanding the meaning of QOL data.

PMID- 8750460
TI  - Quality-of-life end points in cancer clinical trials: the U.S. Food and Drug
      Administration perspective.
AB  - Increasingly, quality-of-life (QOL) end points are being incorporated into
      randomized, controlled clinical trials in oncology. The Oncologic Drugs Advisory
      Committee (U.S. Food and Drug Administration) has recommended that beneficial
      effects on QOL and/or survival be the basis for approval of new anticancer drugs.
      Therefore, from a regulatory standpoint, for drugs that do not have an impact on
      survival, demonstration of a favorable effect on QOL is more important than most
      other traditional measures used to assess efficacy, such as objective tumor
      response. Trials incorporating QOL questions will be evaluated on the basis of
      how well they address the stated objectives. The clinical protocol should
      delineate investigators' hypotheses and choice of validated instruments and
      should specify a detailed statistical analysis plan describing strategies for
      handling missing data. The U.S. Food and Drug Administration welcomes the
      opportunity to explore with investigators the use of QOL instruments in the
      design of cancer clinical trials.

PMID- 8750461
TI  - Costs of quality-of-life research in Southwest Oncology Group trials.
AB  - Quality-of-life (QOL) research in Southwest Oncology Group (SWOG) trials has
      achieved increasing support over the past 5 years. The purpose of this paper is
      to estimate the cost of performing QOL research in SWOG trials. During the month
      of January 1995, we tracked staff time expended for QOL tasks at the SWOG's
      Operations Office and Statistical Center. Of interest was a description of
      average costs per patient enrolled in existing SWOG trials (both open and
      closed), including protocol development, ongoing data monitoring, and QOL data
      analysis. The findings emphasize the personnel-intensive nature of this research
      and highlight the role of "start-up" costs, especially in terms of programmer
      time. It is estimated that average monthly direct costs associated with
      implementing a QOL study and monitoring and analyzing QOL data over the life
      cycles of current and closed SWOG QOL protocols are $7304; a $443 per QOL patient
      total cost figure is also presented. Costs associated with initiating QOL
      research in cooperative groups are substantial (4-5-year start-up investment) but
      are expected to decline after systems for monitoring, retrieving, and analyzing
      QOL data are in place. Funding issues are addressed.

PMID- 8750462
TI  - Modeling health-related quality of life: the bridge between psychometric and
      utility-based measures.

PMID- 8750463
TI  - Taking quality of life into account in health economic analyses.
AB  - Cost-utility analysis is the most commonly used approach to incorporating quality
      of-life considerations into economic analyses in health care. This type of
      analysis produces a ratio of the incremental cost of one intervention over
      another to the incremental benefit produced, measured in quality-adjusted life
      years. To be suitable for use in calculating quality-adjusted survival, quality
      of life must be measured in the form of a utility. Direct utility assessment
      techniques are grounded in decision analytic theory and are conceptually complex
      and impractical for use in the clinical trial setting. Alternatives include
      global rating scale items with appropriate "transformations" and health state
      classification indices. The first cancer trials to collect economic data and
      utilities from patients using these techniques are now under way. These trials
      will serve to answer not only biological questions, but also health policy
      questions about whether the additional cost of the more expensive therapy is
      justified by the benefit it produces in both length and quality of life.

PMID- 8750464
TI  - Measuring quality of life in culturally diverse populations.

PMID- 8750465
TI  - Empirically selected instruments for measuring quality-of-life dimensions in
      culturally diverse populations.
AB  - We describe a process for developing and testing the cultural equivalence of
      quality-of-life (QOL) instruments that may be used across culturally diverse
      populations. QOL instruments dealing with satisfaction with various life domains,
      psychological distress, and physical health and functioning were reviewed by
      African-American and Hispanic community advisory boards, translated into Spanish
      and back-translated to ensure translation adequacy, administered to samples of
      100 patients from each of the ethnic minority populations by indigenous nurse
      interviewers, and examined for psychometric adequacy. Ten QOL measures showed
      adequate reliability and validity for further use in the assessment of QOL with
      African-American and Hispanic patients. Three other measures failed to meet the
      defined standards. A dimension shown to be particularly difficult to address
      across culturally diverse groups is family functioning. Procedures for achieving
      cultural equivalence of QOL measures have been shown to be practical and
      productive. Measures are identified that may be used with some confidence to
      assess varied dimensions of QOL with culturally diverse groups.

PMID- 8750466
TI  - Quality-of-life research in the Pediatric Oncology Group: 1991-1995.
AB  - Quality-of-life end points for cancer clinical trials have received much
      attention in the adult literature. However, within pediatric cancer clinical
      trials, the inclusion of these alternate end points has only recently been
      considered. We review the Pediatric Oncology Group's approach to research in this
      area and describe our guidelines and protocols that incorporate quality-of-life
      end points and several of the methodologic barriers that must be addressed.

PMID- 8750467
TI  - Model for quality-of-life research from the Cancer and Leukemia Group B: the
      telephone interview, conceptual approach to measurement, and theoretical
      framework.

PMID- 8750468
TI  - A cooperative group report on quality-of-life research: lessons learned.

PMID- 8750469
TI  - Cancer and Leukemia Group B (CALGB).

PMID- 8750470
TI  - Eastern Cooperative Oncology Group (ECOG).

PMID- 8750471
TI  - Gynecologic Oncology Group (GOG).

PMID- 8750472
TI  - North Central Cancer Treatment Group (NCCTG).

PMID- 8750473
TI  - Radiation Therapy Oncology Group (RTOG).

PMID- 8750474
TI  - Southwest Oncology Group (SWOG).

PMID- 8750475
TI  - Childrens Cancer Group (CCG).

PMID- 8750476
TI  - Pediatric Oncology Group (POG).

PMID- 8750477
TI  - Quality of life in clinical cancer trials: experience and perspective of the
      European Organization for Research and Treatment of Cancer.

PMID- 8750478
TI  - Assessment of quality of life in clinical trials of the British Medical Research
      Council.
AB  - This article describes aspects of the way the Cancer Therapy Committee of the
      British Medical Research Council incorporates quality-of-life (QOL) assessments
      in randomized clinical trials in patients with cancer. The steps taken in
      incorporating QOL assessments in individual trial protocols are described. The
      aspects described concern problems associated with choice of instruments, time of
      assessment, sample size, and analysis. A protocol for patients with small-cell
      lung cancer that compares oral etoposide with intravenous multidrug chemotherapy
      is used for illustration.

PMID- 8750479
TI  - United Kingdom Cancer Research Campaign approach to quality-of-life research in
      cancer clinical trials.
AB  - Clinical trials of new anticancer therapies form an important part of the
      research activity of the Cancer Research Campaign (United Kingdom), and quality
      of-life (QOL) end points are being increasingly used in the evaluation of new
      treatment approaches. The Campaign has a unique policy of supporting a broad
      range of scientific and clinical research, including psychosocial studies, and
      thus QOL research is generated in a variety of clinical settings. The focus of
      interest for the Cancer Research Campaign lies in QOL design and assessment
      rather than the routine application of QOL protocols. Clinical investigators are
      free to adopt in individual approach, but the Campaign operates a strict peer
      review system in protocol assessment. Some standardization of approach is being
      achieved through consensus of opinion and wide collaboration, both nationally and
      internationally.

PMID- 8750480
TI  - Health-related quality-of-life studies of the National Cancer Institute of Canada
      Clinical Trials Group.
AB  - Since 1989, the National Cancer Institute of Canada Clinical Trials Group (NCIC
      CTG) has been successful in implementing and completing health-related quality-of
      life (HQL) assessments as part of phase III clinical trials. Compliance rates for
      completing HQL instruments remain high, with a minimal amount of missing data. It
      is believed that this success is attributable not only to the high degree of
      commitment to measuring HQL by clinical trials investigators, nurses, data
      managers, and central office administrative staff, but also to the educational
      process that was instituted after the development of a CTG policy for measuring
      HQL. From inception to May 1995, a total of 27 clinical trials with HQL
      assessment have been initiated or completed. In the majority of trials, the core
      HQL instrument is the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire (EORTC QLQ-C30). In addition to answering specific
      questions about HQL in these clinical trials, the trials provide the opportunity
      to do research into the measurement of HQL. Thus, current clinical trials include
      research questions about the appropriate timing of assessments, the reliability
      and validity of the QLQ-C30 and other instruments, the role of HQL data in
      assessing toxicity, and the significance of the results of HQL assessments. It is
      anticipated that this activity not only will be a rich source of information
      about the effects of cancer and its treatment on HQL but also will lead to
      improvements in measuring HQL in oncology.

PMID- 8750481
TI  - [The role of transvaginal sonosalpingography in the evaluation of tubal patency].
AB  - The aim of this work was to evaluate transvaginal sonography (TVS) in the study
      of tubal patency as part of the investigation of female infertility. Fifteen
      women underwent tubal patency by ultrasonography while air and saline solution
      were instilled into the uterus to provide positive contrast. In three cases of
      TVS detection of tubal obstruction the findings were compared with
      hysterosalpingography, which confirmed the presence of the occlusion. In one case
      the exam was suspended for the excessive pelvic pain of the patient. In one
      patient TVS tubal control was impossible for the presence of large multiple
      uterine myomas. Transvaginal sonography with the use of a simultaneous
      intrauterine saline infusion offers certain advantages over
      hysterosalpingography, such as the elimination of iodinated contrast and ionizing
      radiation. TVS provides complete examination of the entire pelvis, thus
      delineating uterine and ovarian abnormalities, and it is more convenient and less
      expensive. It should be performed by an experience sonographist with standard
      sonographic equipment. In conclusion, tubal patency can be performed as an
      outpatient procedure in the routine infertility clinic.

PMID- 8750482
TI  - [Preliminary experience with a new tumor marker in obstetrics and gynecology: UGP
      (Urinary Gonadotropin Protein)].
AB  - AIM: To evaluate the use of UGP (urinary gonadotropin protein) as a tumor marker
      in gynaecologic and obstetric malignant diseases. MATERIALS AND METHODS: The
      study was carried out in the division of Gynaecology and Obstetrics of the
      Ospedali Riuniti in Bergamo. 63 patients, with obstetric or gynaecologic benign
      or malignant diseases, entered the study. 66 healthy volunteers were examined as
      a group-control. In both the groups UGP levels were determined in morning urine,
      using an immunoenzymatic commercial kit. RESULTS: Results, expressed in fmol
      UGP/ml of urin, show that UGP is produced by several neoplasms, but the false
      positive percentage is still high; a higher precision can be obtained with an
      accurate choice of the cut-off value and with a standardization of the analytical
      technics. Besides, the contemporary determination of UGP and CA 125 levels
      reduces the possibility of false-positive and false-negative results.
      CONCLUSIONS: More studies must be carried out to confirm the value of UGP as a
      tumor marker in obstetrics and gynaecology. Anyway, this recently purified
      protein can already be useful, in combination with the usual tumor markers, in
      the prompt diagnosis and management of primary neoplasms or recurrences, with a
      higher sensibility in comparison with traditional clinical and radiological
      examinations.

PMID- 8750483
TI  - [Variations in the pulsatile index of the uterine arteries in postmenopausal
      women receiving hormone replacement therapy].
AB  - The authors studied variations in the pulsatility index of the uterine arteries
      in postmenopausal women who had received hormone replacement treatment (HRT) for
      at least one year and compared them to those in a control group not receiving
      HRT. The results showed a significant variation in this index with the tendency
      to assume lower values compared to the control group, thus resulting in increased
      uterine vascularization, almost resembling that observed during the child-bearing
      period. This drop in the pulsatility index should probably be considered the
      anatomo-functional in patients not receiving HRT.

PMID- 8750484
TI  - [Fibroma in pregnancy].
AB  - In this paper, the authors discuss 51 cases of uterine fibromatosis complicating
      pregnancy. From resulting data, and from an evaluation of the literature data,
      there emerges the present tendency to effect a conservative therapy of fibromas
      complicating a pregnancy.

PMID- 8750485
TI  - [Ovarian tumors in menopausal patients].
AB  - In this paper, the authors discuss 22 cases of ovarian tumefaction in post
      menopausal age examining them clinically vaginal echography and dosages of CA 125
      and 19.9, finding a good correlation between this routine diagnosis and the
      suspician of ovarian neoplasia.

PMID- 8750486
TI  - [Acute pelvic inflammatory disease: comparison of therapeutic protocols].
AB  - Acute pelvic inflammatory disease is a serious medical and economic consequence
      of sexually transmitted diseases among young women. The aim of the study is to
      compare the efficacy and safety of gentamycin plus clindamycin with that of
      ceftazidime plus doxycycline in the treatment of hospitalized patients with acute
      pelvic inflammatory disease. A total of 78 patients with acute PID, hospitalized
      in II Obstretic and Gynecologic Clinic of II University of Naples (Italy),
      entered and randomized into two treatment groups: gentamycin plus clindamycin (N
      = 40) and ceftazidime plus doxycycline (N = 36). Patients were excluded if they
      were pregnant or were not over the age of 16 years of had a history of allergy to
      one of the drugs used in the Study of had hepatic disease or kidney trouble or
      had IUD. Acute PID was diagnosed by the following criteria: 1) lower abdominal
      pain; 2) cervical motion tenderness; 3) adnexal tenderness (all three should be
      present); plus at least one of the following additional criteria: a) temperature
      over 38 degrees C; b) leukocytosis (greater than 10.500 mm3); c) purulent
      material from the peritoneal cavity bt culdocentesis; d) inflammatory mass
      present on binomial pelvic examination and/or sonography; e) erythrocyte
      sedimentation rate > 15 mm/hr. Patients were enrolled into the study after
      obtaining informed consent, pretreatment and posttreatment cultures were obtained
      from the endocervix from Neisseria gonorrhoeae and Chlamydia trachomatis and
      aerobic-anaerobic bacteria. The study has shown that the acute PID has a
      polymicrobal origins. Both antibiotic regimens were very effective in the
      treatment of the PID: a complete recovery was obtained in over 90% of patients.

PMID- 8750487
TI  - [Bioelectric profiles and nutritional status in pregnancy: protocol of a
      multicentric project to measure bioimpedance in pregnancy].
AB  - This paper re-examines the criteria underlying weight increases suggested during
      pregnancy. The distinction is introduced between increase in the lean and fat
      masses in the evaluation of the total weight increase, in order to assess the
      real mother's needs and work out a correct diet. Since one of the main adjustment
      mechanisms by the increase of the circulating mass and, more in general, the
      increase of water in the extracellular compartment, authors propose to use
      impedance measurements to longitudinally monitor the changes in the mother's lean
      mass during pregnancy and at the moment of delivery. The operational protocol of
      a multicentric project is presented, which aims at thoroughly analyzing the
      characterization of the mother's lean mass and its possible changes during
      pregnancy by means of bioimpedance measurements. A sample of 800 pregnant women
      will undergo bioimpedance measurements, 400 of which longitudinally during the
      whole pregnancy and 400 immediately before and after delivery. This study will
      also propose food frequency questionnaires in order to better define the
      nutritional status of pregnant women; moreover, sideremia, transferrin and
      ferritin values will be collected to assess any iron deficiencies in the studied
      population.

PMID- 8750488
TI  - [Cytology based on the Pap test: a 5-year experience at the Department of
      Gynecology and Obstetrics of the Iseo Ospedale Civile].
AB  - The aim of our study was to examine the results we obtained; at the gynaecology
      and obstetrics Department of the Civil Hospital in Iseo, in order to judge the
      course of the cervical lesions during the last 5 years. The place of work was our
      department and service of colposcopy. The patients taking part in the study are
      women in most cases resident in the territory of our USSL and including all the
      different ages. We didn't use any criteria of selection and the women showed
      themselves spontaneously. The reading of pap-test was made at the only referring
      centre. The result was very satisfactory and it confirms the tendency to an
      increase of the dysplasia diagnosed during the early phase of manifestation and a
      decrease of the infiltrating neoplasia diagnosis. In conclusion, we can say that
      the pap-test showed itself to be an indispensable method in the early diagnosis
      of the lesions of the uterine neck. Finally, the early recognition of the
      dysplasie permitted us to carry out some preventive interventions, which are,
      therefore, less maimed for woman, as well as the demolition of the management
      costs of the oncological patient.

PMID- 8750489
TI  - [Episiotomy: clinical, technical and psychological aspects].
AB  - The authors investigate the validity of a selective and not on a basic episiotomy
      utilization. Recent retrospective reports proved episiotomy could have a
      protective effect on 1st and 2nd grade lacerations and a predisposing effect on
      3rd and 4th grade ones. As far as prevention of genital prolapse is concerned,
      few reports now exist that can confirm or deny this role attributed to episotomy.
      Concerning episiotomy efficacy in preventing neurologic damage risks to the fetus
      during labour, no difference was found in Apgar scores and in mortality rates in
      newborns with or without episiotomy, both in preterm labours and at term born
      babies. On the contrary episiotomy possible complications are fairly well
      documented, particularly dispaurenia and sexual dysfunctions on intercourse
      resumption after delivery.

PMID- 8750490
TI  - [Paget disease of the vulva].
AB  - The question of whether vulvar Paget's disease is an intraepidermal disease with
      potential to invade the underlying dermis or a tumor of adnexal origin with
      spread to the overlying epidermis remains to be resolved. The most common
      complaint is pruritus. The lesion is described as red, inflamed or erythematous.
      The delay in diagnosis is considerable in most cases. The disease can be
      diagnosed only by biopsy. The lesion frequently extends beyond the clinically
      apparent borders. The disease without underlying invasive carcinoma appears to
      remain as an intraepithelial malignancy for a long time. The high incidence of
      other malignancies (breast, colon, cervix, ovary) warrants careful examination in
      patients with Paget's disease of the vulva. Close follow-up for a longer period
      of time will be necessary before excluding recurrence. A major goal of
      conservative surgery is to preserve sexual function, normal anatomy and body
      image.

PMID- 8750491
TI  - [Giant pedunculated clustered uterine fibromyoma in hyaline and cystic
      degeneration. Limitations of clinical and instrumental diagnosis].
AB  - The authors report a case of a 46-year-old woman who was checked by integrated
      ultrasound examination, i.e. transabdominal and transvaginal, and by
      abdominopelvic CAT. The examinations, ascertained the presence of a probably
      malignant, voluminous, ovarian, multilobate abdominopelvic neoplasia. On opening
      the belly, it was found that the tumefaction was a voluminous, pedunculate
      uterine myofibroma in clusters starting from the rear isthmian wall while the
      adnexa were normal. The histological examination confirmed that it was a
      "fibromyoma in hyaline and cystic degeneration". The authors conclude that
      although the image diagnostics has reached an extremely high level of precision,
      it is not yet possible to make an absolutely certain diagnosis, either on the
      organ from which a pelvic neoplasia originates or on its biological nature.

PMID- 8750492
TI  - [Hystersoscopy: instrumentation and techniques].
AB  - This paper was presented at the 1st Update Course in Hysteroscopy and
      Microcolpohysteroscopy organised by LAMM and held at the 1st Institute of
      Obstetrics and Gynecology at Policlinico Umberto I in Rome. The paper is divided
      into three sections: the first section describes the technical instruments used
      during hysteroscopy (light source, means of distending the uterine cavity, optic
      systems); the second reports the technique used in hysteroscopic examination: in
      particular, the authors underline the importance where necessary (i.e. in young
      patients with stenosis of the cervical canal and in elderly patients with atrophy
      of the neck of the uterus or conglutination of the external uterine operning) of
      preceding dilatation of the cervical canal by the use of endovaginal
      prostaglandin derivatives in order to render it less traumatic. Moreover, the
      authors attempt to simplify the technique as much as possible so as to render it
      a routine or ambulatorial test; the third section describes complications of the
      hysteroscopic examination, in order of frequency, as well as methods of storing
      and disinfecting the instruments used in hysteroscopy.

PMID- 8750493
TI  - [Diagnosis of omphalocele by transvaginal echography].
AB  - In this paper, the authors discuss the utility of the trans-vaginal probe for an
      early diagnosis of fetal malformation, and specifically for the omphalocele.

PMID- 8750494
TI  - Advances in communication technologies: their application in health promotion and
      education.

PMID- 8750495
TI  - The school environment and health.

PMID- 8750496
TI  - The health and environment interface. Opportunities for prevention and education.

PMID- 8750497
TI  - Bringing people back to health.

PMID- 8750498
TI  - Mycobacterium kansasii infection in squirrel monkeys (Saimiri sciureus sciureus).
AB  - This report documents asymptomatic infections of Mycobacterium kansasii in four
      of five tuberculin positive squirrel monkeys (Saimiri sciureus sciureus). The
      mycobacterial DNA amplified by polymerase chain reaction (PCR) from a bronchial
      lymph node had no affinity for the species specific probes of M. tuberculosis, M.
      avium, and M. intracellulare, thus allowing the presumptive diagnosis of an
      atypical mycobacterial infection. Infection by Mycobacterium kansasii was
      confirmed by culture of bronchial lymph nodes from three monkeys. The source of
      the infection was never identified.

PMID- 8750499
TI  - Effects of age, sex, and heredity on measures of bone mass in baboons (Papio
      hamadryas).
AB  - Bone mass and bone density were estimated in 219 pedigreed baboons (Papio
      hamadryas) by radiographic morphometry of the left second metacarpal. Compact
      bone width (total bone width--medullary canal diameter) and bone ratio (compact
      bone width/total bone width) decreased with increasing age squared in both sexes.
      The heritability of medullary canal diameter was 0.64 +/- 0.11, of compact bone
      width was 0.40 +/- 0.15 and of bone ratio was 0.67 +/- 0.13. The results indicate
      baboons are a useful model for studies of age, sex and genetic effects on bone
      mass.

PMID- 8750500
TI  - Gastrin levels and gastric emptying times in rhesus monkeys with a history of
      acute gastric dilatation.
AB  - Abnormal gastric motility has been suggested as a possible causative factor for
      acute gastric dilatation observed in nonhuman primates. To evaluate gastric
      motility in a colony, fasting serum gastrin immunoreactivity and gastric emptying
      times were assessed in rhesus monkeys that had survived single episodes of acute
      gastric dilatation. These were paired with age- and weight-matched control
      monkeys from the same colony. Neither gastric emptying times nor gastrin assays
      were significantly different between the acute gastric dilatation and control
      groups.

PMID- 8750501
TI  - Simian varicella virus antibody response in experimental infection of African
      green monkeys.
AB  - The humoral immune response to simian varicella virus (SVV) was investigated
      following primary and secondary experimental infection of African green monkeys.
      Neutralization and immunoprecipitation assays were used to determine antibody
      titers to SVV throughout the course of infection. The immune response to specific
      viral polypeptides was analyzed by immunoprecipitation analysis. The results
      demonstrate that the simian varicella model offers a useful approach to
      investigate immune mechanisms in human varicella zoster virus (VZV) infections.

PMID- 8750502
TI  - Arterial vascularization of the gastrointestinal tract in Macaca fascicularis
      (cynomologus monkey).
AB  - We describe the origin, course, and distribution of the arteries responsible for
      vascularization of the subdiaphragmatic gastrointestinal tract of Macaca
      fascicularis as well as the characteristics of the celiac trunk and the superior
      and inferior mesenteric arteries, studied in a series of 50 animals. Detailed
      knowledge of these systems is an essential requirement if experimental surgery is
      to be successfully performed in these laboratory animals.

PMID- 8750503
TI  - Response of cynomolgus macaques to immunization against a synthetic peptide from
      the human zona pellucida.
AB  - This study tested immunogenicity of a synthetic peptide hZP3(327-341) from a
      human zona pellucida (ZP) glycoprotein. After antibody response to various
      peptide-carrier conjugates was assessed in mice, two female cynomolgus macaques
      were immunized with the peptide conjugated to keyhole limpet hemocyanin (KLH). A
      control macaque was immunized with KLH. The peptide was immunogenic in both
      species, and included both B and T cell epitopes since low to moderate titers of
      peptide-specific antibodies and a T cell proliferative response were measured.
      Profiles of ovarian steroid metabolites indicated unchanged ovarian function in
      the macaques, but only the control conceived when bred. Ovarian histology was
      normal except that immunoglobulin was bound to ZP in follicles of the peptide
      immune macaques. ZP from these females bound sperm and induced acrosome reactions
      at rates equal to those of an untreated control. The results support the
      feasibility of an immunocontraceptive vaccine based on autologous ZP peptides.

PMID- 8750504
TI  - Enumeration of lymphokine-secreting cells as a quantitative measure for cellular
      immune responses in rhesus macaques.
AB  - We investigated whether enumeration of lymphokine-secreting T cells can be used
      as a quantitative measure to determine the immunogenicity of foreign proteins in
      rhesus monkeys. In addition, it was assessed whether this approach can supplement
      and/or substitute for the well-established lymphoproliferation assay. Two
      candidate vaccine proteins (e.g., HIV-1 gp120 and HSV-2gD) were used as model
      antigens for immunization. PBMCs from immunized animals were antigenically
      stimulated and evaluated on their proliferative capacity and lymphokine release
      at the single cell level. The experiments showed a close quantitative correlation
      between antigen-triggered proliferative responses and the antigen-induced
      generation of IL-2 and IFN-gamma producing cells (pc). IL-4pc were found to
      appear relatively late after the initiation of antigen exposure. The data
      indicate that ELISPOT assays provide valuable tools for the assessment of the
      antigenicity of foreign proteins in vivo.

PMID- 8750505
TI  - Red cell polymorphisms in nonhuman primates: a review.
AB  - Development as well as current status of the knowledge of nonhuman primate blood
      groups are discussed together with some practical implications of the red cell
      antigen polymorphisms in anthropoid apes, Old and New World monkeys and
      prosimians. Recent data on molecular biology and genetics throw light on the
      relationships among simian and human red cell antigens and their evolutionary
      pathways.

PMID- 8750507
TI  - Quality of life.

PMID- 8750506
TI  - Characterization of the natural immune response of rhesus monkey CD4+ve T cells
      to the bacterial antigen streptolysin O (SLO).
AB  - Rhesus monkeys show a high proliferative T cell response to the bacterial
      exotoxin SLO without prior immunization. The present study was undertaken to
      characterize this naturally present SLO-responsiveness with particular emphasis
      on CD4+ve reactive T cells. It is demonstrated that the frequency of SLO-reactive
      cells in the circulation.ranges between 1 in 75 and 1 in 610 CD4+ve T cells as
      determined with limiting dilution analysis. It is also shown that induction of a
      good proliferative response requires Mhc-DR matching between T cell and the
      antigen presenting cells (APC). Stable and DR-restricted SLO-specific CD4+ve T
      cell lines were generated from CD8 depleted peripheral blood mononuclear cells
      (PBMC). The SLO-reactive CD4+ve cell lines are tentatively characterized as Th1
      like based on the predominant production of interferon-gamma (IFN-gamma) over IL
      4, although this seems contradicted by the IL-4 dependent growth of the lines.

PMID- 8750508
TI  - A bleomycin/ifosfamide/cisplatin regimen exhibits poor activity against
      persistent or recurrent squamous gynecologic cancers.
AB  - Persistent or recurrent squamous malignancies of the female genital tract are
      usually incurable by conventional therapy, and results of single agent
      chemotherapy have been disappointing. We undertook this study to confirm a
      previously reported response rate of 69%, using a regimen of bleomycin 30U,
      ifosfamide 5g/m2 with mesna 6g/m2, and cisplatin 50 mg/m2 (BIP) for recurrent
      cervical cancer. This regimen was used to treat persistent or recurrent squamous
      cancers in women with cervical cancer (n = 11), vaginal cancer (n = 1) and vulvar
      cancer (n = 1). Results were reviewed retrospectively and toxicities graded
      according to the criteria of the Gynecologic Oncology Group. No complete
      responses were seen. One patient had a partial response (10%, 95% confidence
      interval 0-28%). Five patients (50%), exhibiting stable disease during therapy
      with BIP, progressed after cessation of therapy. Of 9 women with symptoms after
      one cycle. Significant toxicities included neutropenic fever (3 grade 3, 3 grade
      4), emesis (1 grade 3), confusion (2 grade 4), vaginal bleeding (2 grade 3), and
      renal failure (1 grade 3). Eight patients were transfused with a total of 28
      units of red cells. After 23 months of follow-up, all patients were dead of
      disease. Mean survival was 10 months. Toxicity associated with this regimen can
      be significant, and results appear no better than those reported with single
      agent therapy.

PMID- 8750509
TI  - Malignant transformation in endometriosis of the urinary bladder: case report of
      clear cell adenocarcinoma.
AB  - Clear cell adenocarcinoma of the urinary bladder is a very rare neoplasm. This
      mullerian tumor frequently arises from ovarian endometriosis. We present a case
      of clear cell adenocarcinoma arising from endometriosis in the bladder; this is
      only the third such case report in the English language literature. Endometriosis
      involves the bladder in only approximately 1% of patients with this disease. The
      patient is a 40 year-old woman who has a history of adenocarcinoma arising from
      endometrial tissue in the bladder. Her tumor invaded the rectum, necessitating an
      anterior resection of the rectum as well as a partial cystectomy and a right
      oophorectomy. This case confirms that the relationship between endometriosis and
      clear cell adenocarcinomas of the female genital tract extends to the urinary
      bladder. Carboplatin chemotherapy was initiated in this patient.

PMID- 8750510
TI  - Pathological aspects of normal-sized ovarian carcinoma.
AB  - Twenty cases of ovarian carcinoma with normal-sized ovaries were examined
      histologically. Fifteen of them had metastatic disease of the peritoneal cavity
      and three of the remaining showed uterine involvement. Only in one case was the
      tumor confined to the ovary, but this patient had experienced systemic
      chemotherapy before surgery. The remaining case had metastasis of the stomach.
      Thus, "normal-sized" ovarian carcinoma has a great tendency to spread externally.
      Histology of the carcinoma was that of common epithelial carcinoma of the ovary
      with variable degrees of differentiation except for three cases of apparent
      ovarian metastasis. No cases of definite mesothelioma with ovarian involvement
      were encountered. A search for determinants of the peritoneal spread was
      performed using immunohistochemistry for p53 and bcl-2 proteins. However, no
      differences were found in the antigen expression between the group with and
      without peritoneal metastasis.

PMID- 8750511
TI  - Presenting symptoms of patients with endometrial carcinoma. Effect on prognosis.
AB  - The aim of the study was to determine the presenting symptoms of endometrial
      carcinoma (EC) patients and to assess their possible correlation with some of the
      standard prognostic factors and with survival. A review of the presenting
      symptoms of 181 EC patients indicated that 69.6% presented with postmenopausal
      bleeding while the remaining women presented with irregular bleeding (21.0%),
      abdominal pain (3.9%) and other (5.5%) symptoms. A significantly (p < 0.001)
      higher percentage of patients presenting with abdominal pain and other symptoms
      were diagnosed with advanced stage disease and they had a lower survival than
      those presenting with post-menopausal or irregular bleeding. Patients presenting
      with irregular bleeding had a significantly (p = 0.002) better survival than
      those presenting with postmenopausal bleeding. However, this effect disappeared
      once age was accounted for in a multivariate analysis. Our findings indicate that
      the type of presenting symptoms may occasionally serve as a preliminary
      prognostic indicator.

PMID- 8750512
TI  - Validity of colour and pulsed Doppler US and tumour marker CA 125 in
      differentiation between benign and malignant ovarian masses.
AB  - BACKGROUND: Colour and pulsed Doppler flow imaging have been proposed as methods
      that may be useful in differentiating benign from malignant ovarian masses. It
      has been hypothesised that the detection of neovascularisation with abnormal, low
      resistance blood flow peculiar to malignant tumours is possible, being
      characterised by angle-independent Doppler indices--PI and RI. The initial
      studies reported cut-off values of 1.0 for PI and 0.4 or 0.7 for RI, with values
      below the cut-off suggestive of malignancy. Tumour marker CA 125 SC was found to
      be elevated in 80-85% of patients with serous epithelial ovarian cancer (90% of
      all ovarian cancers) and in a lower percentage in other ovarian cancers, with
      levels over 35 U/ml suggestive of malignancy. In our study we wanted to determine
      whether colour and pulsed Doppler US and CA 125 SC could be used to differentiate
      benign from malignant ovarian masses and whether, by combining the methods, the
      results could even be improved. METHODS: Ovarian masses identified with
      sonography in 71 patients aged 35 years or more, were confirmed at surgery (n =
      61) or endoscopy (n = 4) or followed up to resolution with US (n = 6). Colour and
      pulsed Doppler US were used to identify intratumoral areas of vascularisation and
      to calculate the lowest PI and RI for each ovarian mass. CA 125 SC were measured.
      RESULTS: In 16 of 18 ovarian malignancies and 28 of 53 benign masses, areas of
      intratumoral vascularisation (colour flow) were detected with colour Doppler US
      (p = 0.002). Mean RI was lower in malignant than in benign masses (p = 0.198), as
      was PI (p = 0.248). Index values displayed considerable overlap between malignant
      and benign lesions and the differences were not significant. Mean CA 125 SC was
      higher in malignant than in benign masses (p = < 0.0001). For cut-off at 35 U/ml,
      SE, SP, PPV and NPV for identification of ovarian cancer were 83%, 74%, 79% and
      75% respectively. Either CA 125 SC > 35 U/ml or intratumoral colour Doppler
      signal was detected in all 18 patients with ovarian cancer, but neither of them
      was detected in 25 patients all of whom had benign tumours. Thus, combining the
      two methods, SE, SP, PPV and NPV for ovarian cancer were: 100%, 47%, 32% and 100%
      respectively. CONCLUSIONS: RI and PI values cannot be used to differentiate
      between benign and malignant ovarian tumours in women over 34 years of age. The
      determination of CA 125 serum level is useful in identification of ovarian cancer
      in women over 35 years of age. CA 125 SC under 35 U/ml together with the lack of
      detectable colour flow in the tumour, can reliably exclude ovarian malignancy in
      women over 35 years of age (NPV = 100%).

PMID- 8750513
TI  - Ichthyosis uteri associated with a uterine squamous papilloma.
AB  - A 60-year-old woman was admitted for postmenopausal vaginal bleeding.
      Hysterectomy specimens showed an intrauterine polypoid mass that was a typical
      papilloma microscopically, accompanying severe ichthyosis uteri. There was no
      sign of dysplasia or malignancy. We observed changes simulating koilocytosis in
      some of the papilloma cells, but these did not stain with antiHPV antibodies
      immunohistochemically.

PMID- 8750514
TI  - Endometrial adenocarcinoma and life expectancy in elderly women.
AB  - One hundred and six patients with endometrial adenocarcinoma, aged over 70 years,
      admitted to Gynaecologic Oncological department of Gynecology and Obstetrics
      Institute of Padua University, from 1/01/1974 to 31/12/1994, were studied. The
      life expectancy of these women was good, with a personalized abdominal or vaginal
      surgery, alone with or without lymphadenectomy, or, in advanced stages,
      associated with integrated therapies. In our case series an increasing frequency
      of this neoplasia in elderly women appears significant.

PMID- 8750515
TI  - Squamous cell carcinoma arising from mature cystic teratoma: a report of three
      cases.
AB  - Cases of squamous cell carcinoma arising from mature cystic teratomas of the left
      ovary are presented. Two of the carcinomas occurred in postmenopausal women 54
      and 71 years old and the third in a menstruating woman 42 years old. The two
      women with well-differentiated squamous cell carcinomas, who had extra ovarian
      extension of the tumor, died four and eight months postoperatively. The third
      woman with a poorly-differentiated squamous cell carcinoma, which was confined to
      the ovary, was alive two years after the operation. The special importance in the
      prognosis and spreading of tumors is emphasized.

PMID- 8750516
TI  - Primary ovarian lymphoma with liver metastases: report of one case.

PMID- 8750517
TI  - Pregnancy following treatment of an adolescent with Yolk sac tumour.
AB  - The Authors present the case of a patient suffering from a highly malignant
      tumour, Yolk sac tumour, who received a combined treatment of operation and
      chemotherapy. The treatment was applied selectively, i.e. surgery was as radical
      and as conservative as deemed necessary. The patient was cured and after getting
      married, she gave birth to a baby girl with pes varus. Because of lack of
      experience with Yolk sac tumours, which up to the cytologic era had had bad
      prognoses, and of insufficient knowledge with the consequences of chemotherapy on
      the generative and reproductive functions of the patients cured, we consider our
      case to be worthy of attention.

PMID- 8750518
TI  - Colposcopy monitoring in pregnancy complicated by CIN and early cervical cancer.
AB  - The aim of the study was the evaluation of the role of colposcopy in the
      diagnosis, monitoring and treatment qualification of CIN and early cervical
      cancer in pregnancy. Thirty pregnant women with these lesions aged 25-39 years
      were diagnosed and observed with the use of colposcopy as the first diagnostic
      step supplemented by cytology and directed biopsy. In 26 cases of CIN and 2 cases
      of microcarcinoma, conization was performed at the earliest 6 weeks after
      delivery. Three groups of lesions were distinguished: 1) progressive, including 2
      (6.6%) cases of CIN progressing to microcarcinoma; 2) regressive, including 6
      (20%) cases of CIN3a, and 3) stationary, including 20 (66%) cases of CIN1-3 and 2
      cases of microinvasion. The majority of women were followed up for 7-35 weeks,
      including the course of pregnancy and 6 weeks prior to treatment. The follow-up
      after treatment was determined firstly every 3, then 6 and finally every 12
      months. Concluding, colposcopy with directed biopsy and complementary cytology
      can be regarded as the best management strategy in the diagnosis of CIN and early
      cervical cancer in pregnancy, as well as in monitoring and treatment
      qualification of these patients after vaginal delivery. CIN of all grades, and
      some cases of early invasion which do not have progressive tendencies can be
      treated 6 weeks after delivery, chiefly by means of diagnostic-therapeutic
      conization.

PMID- 8750519
TI  - "Butterfly" operation vs triple incision technique in vulvar cancer. a comparison
      of morbidity and clinical outcome.
AB  - Two groups (group A = 25 cases and group B = 34 cases) of vulvar cancer patients,
      treated with a modified "butterfly" operation (MBO = group A) and a triple
      incision (TI = group B) technique, were evaluated retrospectively. The aim was to
      compare the two operative methods, regarding perioperative morbidity and clinical
      outcome. The histopathologic and clinical characteristics of the patients were
      comparable, in the two groups. The hospitalization period was significantly
      shorter in group B (TI), both when primary (22 vs 34 days, p < 0.01) or secondary
      (41 vs 55 days, p < 0.05) healing occurred. Local recurrences were quite similar
      in number (A = 5/25, B = 6/34) and were successfully treated. No relapses in the
      remaining skin bridges were observed in group B. The overall survival was similar
      in the two groups (A = 64%, B = 63%). However, LN positive cases had a better (p
      < 0.05) survival when treated by MBO (48% vs 23%).

PMID- 8750520
TI  - Sertoli-Leydig cell tumor of the ovary: a clinicopathologic study of 10 cases.
AB  - Ten patients with Sertoli-Leydig cell tumors of the ovary treated consecutively
      were analyzed retrospectively for clinicopathological characteristics, treatment
      modalities and survival. All patients were subjected to a surgical procedure
      including unilateral salpingoophorectomy (USO) in 5, total abdominal
      hysterectomy, bilateral salpingoophorectomy (TAH+BSO) in 2, TAH+BSO and
      omentectomy and pelvic and paraaortic lymphadenectomy and appendicectomy in 3
      patients. Following surgery, 5 patients were subjected to adjuvant VAC
      (vincristine+actinomycine-D+cyclophosphamide) chemotherapy. Sertoli-Leydig cell
      tumors constitued 0.6% of all ovarian neoplasms in our institution (10/1621). The
      mean age at diagnosis was 28.2 years. Of the patients, 8 had stage IA, one had IB
      and one had stage III disease at surgery. Bilaterality was observed in two
      patients (20.0%). Four patients had poorly-differentiated tumors, of whom 1 had a
      retiform pattern and 1 had a heterologue element, with marked mitosis whereas the
      others had well--or moderately--differentiated tumors. Only one patient presented
      with recurrence during pregnancy and died 16 months after initial surgery. Since
      most of the patients present with stage IA disease, a favorable outcome can be
      achieved in most of them and conservative surgery seems to be the treatment of
      choice in younger patients. However, late recurrences even in early stages,
      especially in patients with poorly-differentiated tumors, can be detected,
      resulting in a fatal outcome despite any form of aggressive therapy.

PMID- 8750521
TI  - Ovarian surface serous papillary carcinomas: a clinicopathologic study.
AB  - Between 1982 and 1992, 129 patients with malignant epithelial ovarian tumors were
      reviewed with identification of 10 patients having surface papillary serous
      carcinoma of the ovary and one having peritoneal papillary carcinoma. The gross
      operative specimens, histopathologic condition, and treatment records were
      reviewed. All patients had disease involving the omentum, and the abdominal and
      pelvic peritoneum, and they all corresponded to stage III, according to FIGO. The
      median age at presentation was 58-years (age range, 43 to 73 years). All patients
      had a total abdominal hysterectomy and bilateral salpingo-oophorectomy, and all
      received chemotherapy. The median survival time for all patients was 15 months.
      Three patients are alive 3 to 4 years after the initial diagnosis. In conclusion,
      surface serous ovarian cancers and peritoneal papillary serous cancers have
      common histologic appearance and the same responsiveness to surgical therapy and
      to chemotherapy and should be treated similarly.

PMID- 8750522
TI  - Breast cancer measurements with magnetic resonance imaging, ultrasonography, and
      mammography.
AB  - BACKGROUND: Accurate measurement of the size of breast cancers becomes more
      important as breast cancer therapy advances. This study reports the accuracy of
      magnetic resonance imaging (MRI), ultrasonography and mammography for measuring
      the largest breast cancer diameter in comparison to the pathology measurement.
      MATERIALS AND METHODS: Fourteen breast cancers were examined in 13 women with
      MRI, ultrasonography and mammography. The age range was 31-73 (mean 56). Six of
      the cancers were in premenopausal women. The MRI was performed with the
      intravenous injection of gadolinium based contrast agent and a three dimensional
      fast spoiled gradient echo sequence with fat suppression. The largest cancer
      diameter was measured with each imaging technique and compared to the largest
      cancer diameter measured at pathology. RESULTS: At pathological examination
      cancers ranged from 0.6 to 6 cm (mean 2.2) in largest diameter. MRI measurements
      had the highest correlation coefficient (r = 0.98) and the smallest standard
      error (0.34). Ultrasonography measurements had a correlation coeffient of r =
      0.45 and a standard error of 0.78. Mammography measurements had a correlation
      coefficient of r = 0.46 and a standard error of 1.04. CONCLUSIONS: MRI was more
      accurate than ultrasonography and mammography in measuring the largest cancer
      diameters in this group of women. This was particularly evident for several
      larger cancers, and a postchemotherapy cancer.

PMID- 8750523
TI  - Ovarian irradiation and prednisone following surgery and radiotherapy for
      carcinoma of the breast.
AB  - Following mastectomy, patients aged 35 to 76 years with operable breast cancer
      underwent postoperative irradiation of the chest wall and regional lymph nodes.
      They were then assigned at random to receive no further therapy (NT), ovarian
      irradiation (R) 2000 rads in 5 days, or ovarian irradiation in the same dosage
      plus prednisone (R + P) 7.5 mg daily for up to five years. A total of 703
      eligible patients received the randomly assigned treatment. The median follow up
      was 21 years with a range of 14 to 25 years. Overall, there was a delay in
      recurrence (p = 0.03) and survival was prolonged (p = 0.19) for patients who
      received R, but in neither case was the difference significant after adjusting
      for the multiplicity in our data. Overall, patients who received R + P
      experienced a significant delay in recurrence (p = 0.0003) and a significantly
      prolonged survival (p = 0.005), even after adjusting for multiple comparisons. In
      premenopausal patients who received R, the recurrence of breast cancer was
      delayed and survival prolonged, but not significantly. In premenopausal women
      aged 45 years or more, R + P therapy significantly prolonged survival (p =
      0.0004), while the delay in recurrence although significant (p = 0.02) was only
      marginally so after allowance for multiple comparisons. No value was demonstrated
      for ovarian irradiation with or without prednisone therapy in postmenopausal
      patients. A new finding in this review was that contralateral breast cancer as
      the first failure was reduced by R + P compared to NT in the overall group.

PMID- 8750524
TI  - Exercise during adolescence and its effects on mammary gland development,
      proliferation, and nitrosomethylurea (NMU) induced tumorigenesis in rats.
AB  - The purpose of this investigation was to determine the effects of moderate
      intensity exercise training during peripuberty on nitrosomethylurea (NMU) induced
      mammary tumorigenesis and to assess the effects of this activity on mammary
      epithelial cell proliferation and mammary gland development in rats. Female
      Sprague Dawley rats were divided into two groups, sedentary and exercised. The
      rats were exercised five times per week from 21 to 50 days of age on a
      progressive treadmill training program with a final workload of 18 m/min at 15%
      incline for 60 min a day. At fifty days of age eight rats from each group were
      sacrificed to determine the effects of exercise on mammary gland labelling index
      and development scores. The remaining animals were given NMU at a concentration
      of 50 mg/kg body weight. The experiment was terminated 24 weeks post carcinogen
      administration, and cancer incidence, multiplicity, and latency were analyzed.
      The total tumor number per group was reduced by exercise (58 vs. 33 carcinomas p
      < 0.05). This corresponded to a significantly higher number of tumors/animal in
      the sedentary rats compared to those that were exercised prior to NMU
      administration. However latency period (124.9 +/- 4.3 vs. 125.2 +/- 6.4) and
      final incidence (68.9% vs. 61.5%) were not significantly different in sedentary
      vs. exercised rats. There were no significant differences in mammary gland
      developmental scores (4.1 +/- 0.24 vs. 4.4 +/- 0.26) or labelling index of
      mammary epithelial cells in either ducts or lobuloaveolar units (ductal 41.5 +/-
      4.7 vs. 39.4 +/- 5.7; lobuloalveolar 38.5 +/- 4.1 vs. 47.7 +/- 5.7) between the
      two groups. The results of this study suggest that although exercise prior to
      carcinogen administration has an effect on mammary tumorigenesis, these effects
      do not appear to be related to exercise-induced changes in mammary gland
      development.

PMID- 8750525
TI  - In vitro effects of eicosanoid synthesis inhibitors in the presence of linoleic
      acid on MDA-MB-231 human breast cancer cells.
AB  - We investigated the effects of cyclooxygenase and lipoxygenase inhibitors in the
      presence of linoleic acid (LA), as well as the direct effects of prostaglandin E
      (PGE) and leukotriene B (LTB) on a human breast cancer cell line (MDA-MB-231) in
      vitro. Piroxicam, esculetin, and nordihydroguaiaretic acid (NDGA) suppressed cell
      growth and thymidine incorporation. However, a low concentration (1 microgram/ml)
      of indomethacin (INDO) stimulated cell growth and thymidine incorporation, while
      a high concentration of INDO (30 micrograms/ml) inhibited both. Esculetin and
      NDGA reduced the secretion of LTB, whereas piroxicam reduced the secretion of
      PGE. INDO reduced the secretion of PGE, but a low concentration of INDO increased
      the secretion of LTB. Consequently, cell growth was correlated with the PGE
      and/or LTB concentrations when the cells were treated with these cyclooxygenase
      or lipoxygenase inhibitors. On the other hand, exogenous PGE2 partially reversed
      the inhibition of thymidine incorporation caused by INDO, whereas LTB4 exerted a
      similar effect in the case of esculetin or NDGA. The reversibility of the
      piroxicam effect with PGE2 is not convincing. Therefore, it is suggested that the
      growth of MDA-MB-231 cells in vitro is affected by both the lipoxygenase and
      cyclooxygenase products, probably the other eicosanoids rather than PGE2 and
      LTB4.

PMID- 8750526
TI  - An analysis of the cost of clinical surveillance after primary therapy for women
      with early stage invasive breast cancer.
AB  - Routine surveillance for distant metastases in women with early stage breast
      cancer has limited clinical utility and can result in large medical care costs.
      In order to estimate breast cancer surveillance costs, we used the results of a
      survey administered to a random sample of physician members of the American
      Society of Clinical Oncology. The survey measured the frequency in which
      radiographic and laboratory tests are ordered for postmenopausal women with stage
      I or II breast cancer after the completion of surgery and radiation or adjuvant
      chemotherapy if indicated. There were 209 completed surveys representing a
      response rate of 48%. The volume of tests ordered was expressed in terms of
      Medicare's relative value units (RVUs) and 1993 cost equivalents. The mean total
      RVUs over 5 years post-diagnosis was 43.8 (interquartile range 30.1-54.2) which
      represents a cost of $1369 using the 1993 Medicare conversion factor of $31.249.
      A cumulative logistic regression model categorized RVUs according to intensity of
      care (minimal, average, and intensive). While medical oncologists compared to
      surgeons and radiation oncologists, and physicians practicing in the Northeast
      and Midwest, compared to those practicing in the South and West, were more likely
      to adopt an intensive practice style, these differences were not statistically
      significant (p = 0.1). None of the other provider characteristics evaluated,
      including gender, prior experience, and practice type, had a significant effect
      on physician practice in a multivariate model. The data showed a wide variation
      among providers in surveillance practice patterns that was largely unexplained by
      physician demographics. These results are consistent with the physician practice
      style hypothesis which suggests that wide variations in treatment patterns result
      from uncertainty regarding effectiveness of care.

PMID- 8750527
TI  - A case-control study of reproductive variables, alcohol, and smoking in
      premenopausal bilateral breast cancer.
AB  - Premenopausal bilateral breast cancer is characterized by a strong family risk,
      and, consequently, a high probability that inherited susceptibility genes may be
      segregating in these families. Determining whether risk factors that affect other
      breast cancer cases have a similar effect in the etiology of bilateral breast
      cancer is of interest. Therefore, as part of an ongoing genetic-epidemiologic
      study of premenopausal bilateral breast cancer, we conducted a case-control
      analysis of reproductive variables, benign breast disease, alcohol, and smoking.
      Cases had premenopausal bilateral breast cancer, and their unaffected sisters
      served as controls. A set of reproductive variables--including earlier age at
      menarche, nulliparity, and late age at first full term pregnancy--appeared to
      increase the risk of breast cancer; the corresponding confidence limits, however,
      were wide and straddled the null. In addition, other variables associated with
      increased premenopausal bilateral breast cancer risk were: use of oral
      contraceptives, history of benign breast disease, and high alcohol consumption.
      We found no positive association for smoking. Nulliparity and late age at first
      full-term pregnancy appeared to have different effects in women with family
      histories of breast cancer than in women without such a history. We detected no
      substantial effect modification for the other risk factors. In general, risk
      factors previously identified for breast cancer (usually postmenopausal,
      unilateral cases) appear also to increase the risk for premenopausal, bilateral
      breast cancer.

PMID- 8750528
TI  - Long term prognostic value of growth fraction determination by Ki-67
      immunostaining in primary operable breast cancer.
AB  - An immunohistochemical determination of the growth fraction (GF) with the Ki-67
      monoclonal antibody has been performed in a prospective series of 140 patients
      with primary operable breast carcinoma. GF ranged from 0% to 43% Ki-67 stained
      cells with a median value of 8%. High GF (> 8%) was significantly associated with
      axillary node involvement (p = 0.006), aneuploidy (p = 0.008), histologic grade
      (p = 0.03), and S-phase fraction > 5% determined by flow cytometry (p = 0.01).
      After a median follow-up of 6 years, the univariate analysis did not show
      significant correlation between high GF and worse relapse-free survival (p =
      0.10) or shorter overall survival. However, a multivariate analysis on relapse
      free survival, performed in 127 comparable patients, showed that GF was an
      independent predictive factor (p = 0.03) together with nodal status (p =
      0.00001), age under 45 years (p = 0.0008), and chemotherapy (0.006). In node
      negative patients, GF was still an independent prognostic indicator (p = 0.002)
      together with age under 45 years (p = 0.0003). Tumor proliferative activity
      evaluated by the monoclonal antibody Ki-67 appears to be an effective indicator
      of prognosis in breast cancer and could be of assistance in the decision making
      of adjuvant therapy in node negative patients.

PMID- 8750529
TI  - INT2 and ERBB2 amplification and ERBB2 expression in breast tumors from patients
      with different outcomes.
AB  - The relationships of INT2 and ERBB2 amplification and of ERBB2 overexpression in
      primary breast tumors to prognostic factors, recurrence, and survival have
      generated considerable controversy. The rationale for this study is that long
      term, recurrence-free survival is a more direct criterion for testing the
      validity of a tumor marker than correlation either with prognostic factors or
      with short-term recurrence and survival. We examined the association of
      recurrence with INT2 and ERBB2 amplification and ERBB2 expression by comparing
      primary breast tumors from patients surviving without recurrence for > or = 8.5
      years after diagnosis, the LTS group, to tumors from patients recurring within
      two years, the RR group. The RR (N = 63) and LTS (N = 61) samples were coded and
      examined for amplification by Southern blotting and for expression by
      immunohistochemistry. Comparison between the RR and LTS groups demonstrated that
      INT2 amplification was associated with a significantly (P = 0.018) higher (5.6
      fold) risk of recurrence, an association that remained significant after
      controlling for lymph node (LN), tumor size (TS), and histograde (HG) status.
      ERBB2 amplification and expression were not associated with a higher recurrence
      risk. Survival analyses within the RR group, however, demonstrated significantly
      shorter survival time among cases with than without ERBB2 amplification (P =
      0.018, median survival 16 vs 25 months), or ERBB2 expression (P = 0.019, median
      survival 15 vs 25 months), but not INT2 amplification. Univariate Cox
      proportional hazards regression models also demonstrated significantly shorter
      survival among cases with ERBB2 amplification (P = 0.016) or expression (P =
      0.049), that remained significant in multivariate analyses (P = 0.022) for ERBB2
      amplification. These results indicate a significant positive association between
      INT2 amplification and risk for tumor recurrence in the RR as compared to the LTS
      group. The relationship of ERBB2 amplification or overexpression to patient
      outcome is more complex. ERBB2 amplification and expression have a significant
      relationship with shorter survival among patients recurrent within two years, but
      their occurrence in tumors from women surviving without recurrence for > or = 8.5
      years suggests that ERBB2 status is not predictive of shorter survival for all
      breast cancers.

PMID- 8750530
TI  - Cell cycle expression of steroid receptors determined by image analysis on human
      breast cancer cell line: a hypothesis on the effects of antiestrogens.
AB  - Tamoxifen is the widespread anti-hormonal compound used for the treatment of
      human breast cancer. It is admitted that its effects are mediated via estrogen
      receptors (ER) but the molecular basis of its activity has yet to be clearly
      defined. In this work, we have developed a new image cytometry procedure in order
      to clarify the interactions between steroid receptors and tamoxifen at the cell
      cycle kinetic level. On untreated cells, an increase of ER level and a decrease
      of progesterone receptor (PR) level during the G0/G1 phase were demonstrated.
      Then, the ER and PR levels fell during the S-phase until the beginning of G2/M
      phase, where an increase was observed, especially for PR. These results suggest
      that ER is synthesized preferentially during the G0/G1 transition and PR during
      the S/G2 transition. After short-term tamoxifen treatment an augmentation of ER
      level was observed which was not dose-dependent, suggesting an increase in
      receptor translation rather than an augmentation of ER synthesis. PR level
      declined in the majority of the population leading to a selection of a subset of
      proliferating PR negative cells after treatment. These data demonstrate that the
      synthesis of steroid receptors is linked with the progression of cells through
      the cell cycle and indicate that tamoxifen blocks MCF-7 cells in G1 via its
      interactions with ER. Our multifluorescence imaging procedure appears to provide
      a rapid and quantitative approach which is useful for investigating alterations
      in steroid receptors after endocrine treatment.

PMID- 8750531
TI  - Differential distribution of ErbB-2 and pS2 proteins in ductal carcinoma in situ
      of the breast.
AB  - We examined the expression of ErbB-2 and pS2 proteins in 59 ductal carcinoma in
      situ (DCIS) of the breast, either pure DCIS or DCIS associated with invasive
      carcinoma, using immunohistochemical staining of paraffin-embedded sections.
      Positive staining for ErbB-2 and pS2 proteins was noted in 32% (19/59) and 46%
      (27/59) of DCIS, respectively. An inverse relationship between ErbB-2 and pS2
      status in DCIS was observed (p < 0.01). From the viewpoint of histological
      subtype, the prevalence of ErbB-2 protein expression was significantly higher in
      the comedo subtype than the cribriform-micropapillary subtype. The prevalence of
      immunoreactivity for ErbB-2 in solid subtype was intermediate between those of
      the other two groups. In contrast, the prevalence of pS2 expression was
      significantly lower in the comedo subtype than in the cribriform-micropapillary
      subtype. Again, the prevalence of pS2 protein expression in the solid subtype was
      intermediate between those of the other two subtypes. Our results suggest that
      DCIS is biologically heterogeneous with regard to such marker substances. This
      has possible implications for management of these lesions.

PMID- 8750532
TI  - Phase II study of mitoxantrone, 5-fluorouracil, and levo-leucovorin (MLF) in
      elderly advanced breast cancer patients.
AB  - We have carried out a phase II trial to evaluate the efficacy and toxicity of a
      combination therapy consisting of mitoxantrone 10 mg/sqm i.v. on day 1, levo
      leucovorin 250 mg/sqm administered over 2 hours and 5-fluorouracil 500 mg/sqm
      i.v. push after the first hour of levo-leucovorin infusion, on days 15-16 (MFL)
      in patients aged more than 65 years. 24 patients with advanced breast cancer
      entered the study: 16 aged 65-70 yrs, 4 patients 70-75 yrs, and 4 > 75 yrs.
      Median PS was 1 (range 0-2); sites of metastases were: bone 14 patients, viscera
      14 patients, soft tissue 11 patients, and CNS 1 patient. A median number of 6
      cycles (range 3-9) was administered. All patients were evaluable for response and
      toxicity; partial response was obtained in 12 (50%) patients (95% C.I 30-70),
      stable disease was observed in 9 patients (37.5%), while 3 patients (12.5%)
      progressed. Median progression-free survival and survival were 9 months (range 2
      14) and 14 months (range 5-36), respectively. Toxicity was generally mild and the
      most frequently observed side-effects were WHO gr. 1-2 leukopenia in 6/24 (25%)
      patients and gr. 1-2 emesis in 10/24 (41.6%) pts. 1 patient pretreated with
      doxorubicin cumulative dose of 240 mg/sqm showed clinical signs of congestive
      heart failure (NYHA grade 1) after the fifth cycle of treatment. MFL is a well
      tolerated regimen and could represent a safe and effective treatment in older
      advanced breast cancer patients.

PMID- 8750533
TI  - [Multicenter transversal study of tuberculosis and drug resistance in Madrid
      (October 1993-April 1994)].
AB  - BACKGROUND: The aim of this study was to know the demographic profile of the new
      cases of tuberculosis (TB) and evaluate the current status of resistance to
      antituberculous drugs in Madrid, Spain. METHODS: A transversal study was carried
      out in 8 hospitals (6 general hospitals) during 6 months. The clinical data of
      patients over 14 years old who presented a positive culture for Mycobacterium
      tuberculosis were collected in a protocolized method; the study on sensitivity to
      5 drugs was independently and centrally performed (proportions method). RESULTS:
      467 patients (339 from general hospitals), were included. In respect to the
      latter patients, 71% were under the age of 45 years and 36% presented coinfection
      with the human immunodeficiency virus (HIV). A sensitivity study was performed in
      419 strains. Forty strains showed resistance to one or more of the
      antituberculous drugs; 13 were from the same center (CIC) in which a nosocomial
      outbreak of multiresistent TB had been detected among HIV infected patients.
      Resistence to more than one drug was observed in 29 cases (6.9%) and to
      rifampicine (RIF) and isoniacide (INH) in 24 patients (5.7%). On excluding the
      patients from the CIC these values were 16 (4.1%) and 13 (3.3%), respectively.
      Ninety-two percent of the strains with resistence to RIF + INH were from HIV
      positive patients. The rate of primary resistence to iNH in the patients with TB
      without HIV infection was 2.7%. This rate was 9.3% in those with HIV infection,
      and was 5.7% on excluding CIC cases. In patients with HIV infection most of the
      strains with primary resistence to INH also presented primary resistance to RIF.
      CONCLUSIONS: More than one third of the patients with TB diagnosed in the general
      hospitals in Madrid, presented coinfection with HIV. In this population, the
      initial treatment for TB should probably begin with 4 drugs while awaiting the
      obliged sensitivity study.

PMID- 8750534
TI  - [Myocardial structure and study of arrhythmias during ambulatory
      electrocardiographic monitoring in mild essential hypertension].
AB  - BACKGROUND: The development of arrhythmias in patients with high blood pressure
      has been related to the presence of left ventricular hypertrophy. The aim of this
      study was to determine the presence and relationship between left ventricular
      hypertrophy and arrhythmias in patients with slight arterial hypertension.
      METHODS: One hundred and two individuals (54 males and 48 females), 51 of whom
      were hypertensive and 51 normotensive, were included in the study. None of the
      subjects had received antihypertensive treatment. Twenty-four hour
      electrocardiographic registry, echocardiogram and ambulatory blood pressure
      monitorization were performed. RESULTS: Fifty one percent of the hypertensive
      individuals had left ventricular hypertrophy (LVH) versus 18% of the normotensive
      subjects. Supraventricular and ventricular arrhythmias were equally frequent in
      the hypertensive and the normotensive subjects as were the episodes of ST
      depression (7.8% versus 9.8%, respectively). Both types of arrhythmias were
      correlated with the age of the hypertensive subject. Twenty-seven of the
      hypertensive subjects had white coat hypertension. The left ventricular mass in
      these subjects was similar to that of the hypertensive subjects with maintained
      hypertension and both were greater than the normotensive subjects. In regard to
      the frequency of LVH in the hypertensive subjects with maintained hypertension,
      15 (62.5%) did not differ from either the LVH in white coat hypertensive subjects
      11 (40.7%) or in regard to the frequency of supra and ventricular arrhythmias. On
      multivariate analysis both types of arrhythmias correlated with the index of
      ventricular mass in the hypertensive patients in both males and females.
      CONCLUSIONS: Left ventricular hypertrophy may develop early in hypertension
      although it is not related to a greater frequency of arrhythmias in patients with
      slight arterial hypertension.

PMID- 8750535
TI  - [Adverse reactions to different types of influenza vaccines].
AB  - BACKGROUND: The objective was to establish the rate of adverse reactions to the
      various influenza vaccines (whole, fractionated and subunits). METHODS: The
      prescription and the adverse reactions to 21,391 influenza vaccinations carried
      out in the Avila province, Spain, were studied using a questionnaire filled in at
      the moment when the vaccine was administered and one or two weeks afterwards. The
      statistical tests used were the residual chi 2 and the multivariate logistic
      regression analysis. RESULTS: Adverse reactions were observed in 28.8% of the
      cases. Local pain (18.8%) and redness (13.4%) were the most frequent reactions.
      3% of the vaccinated people had fever, 4.9% general malaise and 1.2% were
      confined in bed. Other adverse reactions were observed in 5.4% of the persons.
      The differences between the various vaccines were significant (whole vaccines
      with a rank, according to the trademark, 27.7% to 35.8%; fractionated, 27.3% and
      subunits, 24.4%). CONCLUSIONS: Inactivated whole and fractionated vaccines cause
      more adverse reactions, mainly local, than subunit vaccines. There are no
      differences in adverse sistemic reactions. Occupational prescription and vaccines
      administered to persons older than 65 were the lowest risk prescriptions.

PMID- 8750536
TI  - [Multidrug-resistant tuberculosis. Remarks and reflections on a controversial
      subject of current utmost importance].

PMID- 8750537
TI  - [Road to 2000].

PMID- 8750538
TI  - [Thymus carcinoid associated with type 1 multiple endocrine neoplasm syndrome].
AB  - Thymus carcinoid tumors are unusual and can be differentiated from thymomas by
      clinical, histological and prognostic characteristics. The clinicopathological
      findings of a new case of carcinoid tumor of the thymus associated with type 1
      multiple endocrine neoplasm, the presentation of which was conditioned by its
      metastasis, is herein presented.

PMID- 8750539
TI  - [Reflections on the clinical trial law].

PMID- 8750540
TI  - [Hepatocyte transplantation: current status].

PMID- 8750541
TI  - [AIDS and primary lateral sclerosis?].

PMID- 8750542
TI  - [Elevation of muscular enzymes in idiopathic hypoparathyroidism].

PMID- 8750543
TI  - [3,4-diaminopyridine in the treatment of myasthenic syndromes. Practical
      aspects].

PMID- 8750544
TI  - [Bacteremia caused by Achromobacter xylosidans].

PMID- 8750545
TI  - Quantitative analysis of the spinal cord motoneuron under chronic compression: an
      experimental observation in the mouse.
AB  - We investigated quantitative changes in spinal cord motoneurons following chronic
      compression using a mouse model of cervical cord compression. Twenty-five tip-toe
      walking Yoshimura (twy) mice with calcified mass lesions compressing the spinal
      cord posterolaterally at the C1-C2 vertebral levels were compared with five
      Institute of Cancer Research (ICR) mice that served as controls. Spinal cord
      motoneurons in the anterior grey horn between the C1 and C3 spinal cord segments
      were Nissl-stained and counted topographically and then analysed in relation to
      the extent of spinal cord compression. The number of motoneurons in C1-C3 spinal
      cord segments decreased significantly with a linear correlation with the
      transverse area of the spinal cord when the cord was compressed to 50-70% of
      control values. A significant reduction in the number of motoneurons occurred at
      the C2-C3 spinal cord segment compressed at the C1-C2 vertebral level. In
      contrast, at the level rostral to the C1 vertebra, the number of motoneurons
      increased significantly in proportion to the magnitude of compression. The
      current study demonstrates that a number of neurons, morphologically consistent
      with anterior horn cells, were observed at a rostral site absolutely free of
      external compression where no such cells normally exist.

PMID- 8750546
TI  - Intravenous immunoglobulin therapy in amyotrophic lateral sclerosis.
AB  - Seven consecutive patients with amyotrophic lateral sclerosis (ALS) were treated
      with intravenous immunoglobulins (IVIg; 0.4 g/kg per day for 5 consecutive days
      followed by monthly 2-day infusions at the same daily dosage) continued with oral
      cyclophosphamide (1-2 mg/kg per day), for 4-13 months (mean 8.1). Response to
      treatment was assessed by means of the Medical Research Council (MRC) rating
      scale for muscle strength on 40 muscles (10 per limb), a clinical scale for
      bulbar function and a modified Rankin disability scale. All patients continued to
      deteriorate during treatment on as regards both their MRC score and either their
      bulbar or Rankin score or both. The progression of the disease during treatment,
      expressed as the monthly variation in MRC score (mean = -2.71; SD = 1.36), was no
      slower than that estimated before therapy (mean = -1.81; SD = 0.93). Even if the
      results of this small, uncontrolled study do not permit the exclusion of an
      effect of IVIg on the progression of ALS, they also do not provide any evidence
      that this expensive form of therapy consistently slows the course of the disease.

PMID- 8750547
TI  - Dissection of the vertebral artery with cervical nerve root lesions.
AB  - Vertebral artery dissection may cause upper limb peripheral motor deficit. We
      report three young patients presenting with nuchal pain followed by a nearly
      painless proximal paresis of the arm several days later. The cause, as detected
      by colour-coded Duplex sonography and MRI, was an extracranial dissection of the
      vertebral artery. The proximity of the intervertebral segment to the vertebral
      artery and the nerve roots indicated that compression by an intramural haematoma
      was the likely cause of the disorder. Subsequent examinations during
      anticoagulation treatment showed almost complete disappearance of the intramural
      haematoma and of the neurological deficits within a few weeks. We believe that
      the occurrence of an upper limb peripheral motor deficit should be added to the
      spectrum of potentially misleading signs of vertebral artery dissection.

PMID- 8750548
TI  - Glucocorticoid-sensitive hereditary inclusion body myositis.
AB  - We report a hereditary muscle disorder with features of inclusion body myositis
      (IBM) in two adult sisters with slowly progressive asymmetrical muscle weakness.
      The findings of light microscopic and ultrastructural investigations of muscle
      biopsy specimens were consistent with a diagnosis of IBM. Both patients improved
      and stabilized on immunosuppressive treatment with corticosteroids and
      azathioprine. This differentiates our patients from other sporadic and familial
      cases of IBM. Clinical and histological features are described and compared with
      those of other previously reported families with IBM.

PMID- 8750549
TI  - Diaschisis of specific cerebellar lobules: pontine haematoma studied with high
      resolution PET and MRI.
AB  - Cerebellar glucose metabolism was studied in one patient with a hemipontine
      haematoma in order to investigate remote metabolic effects within the cerebellar
      lobules. In the patient, who suffered a circumscribed hemipontine haemorrhage,
      and in three normal subjects cerebellar glucose metabolisms was studied using 18F
      2-fluoro-2-deoxy-D-glucose and high-resolution positron emission tomography
      (PET). Regions of interest were placed on sagittal brain slices of co-registered
      magnetic resonance images for quantitative evaluation of glucose metabolism in
      each cerebellar lobule. Interruption of corticopontine fibres caused inactivation
      of pontine nuclei with subsequent contralateral cerebellar diaschisis, mainly in
      the anterior lobe and the posterior portion of the quadrangular lobule. Damage
      within the ponto-cerebellar part of the cortico-ponto-cerebellar pathway, e.g.
      pontine nuclei and crossing ponto-cerebellar fibres from contralateral pontine
      nuclei, led to ipsi- and contralateral cerebellar diaschisis within the
      semilunar, gracile and biventral lobules. High-resolution PET is capable of
      demonstrating bilateral diaschisis involving specific cerebellar lobules to a
      different degree that is consistent with the pontine anatomy of the cortico-ponto
      cerebellar pathway and with the location of the haemorrhagic lesion.

PMID- 8750551
TI  - Botulinum toxin in the therapy of gustatory sweating.
AB  - Three patients suffering from gustatory sweating following trauma to the
      preauricular region from a bullet wound or parotid gland surgery were treated by
      intracutaneous injection of botulinum toxin A. Within 2 weeks, gustatory sweating
      in the area injected completely ceased in all patients with no side-effects. The
      efficacy of treatment was confirmed by repeated Minor's iodine starch tests. So
      far, sweating has not recurred during a follow-up period of up to 8 months.
      Botulinum toxin appears to be a promising new drug for the treatment of this
      autonomic disorder.

PMID- 8750550
TI  - Neurological complications of liver transplantation.
AB  - We examined 199 consecutive patients who underwent 220 liver transplantations, to
      define the type, frequency and aetiology of posttransplant neurological
      complications and their prognostic value. We found neurological complications in
      63 patients (32%), mostly involving the central nervous system. The most frequent
      complications were mental status changes ranging from delirium to coma and
      seizures. The aetiology was multifactorial, cyclosporin A neurotoxicity being the
      main cause. Patients with neurological complications had a higher mortality rate
      than those without. In our series, neurological complications represented a major
      medical problem with increased morbidity and mortality.

PMID- 8750552
TI  - Guillain-Barre syndrome: a series observed at Riyadh Armed Forces Hospital
      January 1984--January 1994.
AB  - A consecutive series of 47 hospitalized cases of Guillain-Barre syndrome seen
      over a 10-year period was analysed with respect to: (1) age and sex; (2)
      antecedent events and seasonal distribution; (3) patterns of clinical
      presentation; (4) CSF and neurophysiological findings; (5) results of treatment
      with plasma exchange; and (6) outcome. Twenty-two were children, 20 middle-aged
      and 5 aged; 37 were male and 10 were female. The most frequent antecedent event
      was upper respiratory tract infections; a seasonal peak incidence was found in
      winter. Clinical, CSF and neurophysiological findings concurred with those in the
      Western literature; 79% of the cases were severe. Plasma exchange performed
      within the first 2 weeks of onset benefitted in the short-term outcome, i.e.
      improvement by 1 grade at 4 weeks, but the long-term benefit, i.e. the ability to
      regain independent locomotion, was questionable. Plasma exchange helped in
      curtailing the time to walking unaided but had no benefit on the duration of
      artificial ventilation. Factors associated with an adverse outcome were: age over
      15 years, severity of motor electrodiagnostic findings (especially a decreased
      distal CMAP amplitude and EMG signs of acute denervation), requirement for
      ventilation and slow progression (>3 weeks) to maximum deficit. After a mean
      follow-up of 11 months, 55% of the patients regained independent locomotion,
      which is a comparatively low proportion.

PMID- 8750553
TI  - Pain in multiple system atrophy.
AB  - Pain is a recognized feature of idiopathic Parkinson's disease (IPD) but has
      never been studied in multiple system atrophy (MSA), the commonest cause of
      atypical parkinsonism. We retrospectively analysed histories of pain in 100
      consecutive cases of clinically probable MSA. Details were obtained from the
      medical records of 100 patients with MSA, comprising 82 with the striatonigral
      degeneration (SND) type and 18 with the olivopontocerebellar atrophy (OPCA) type
      of MSA. Pain was reported in 47% of the MSA patients. It was classified as
      rheumatic in 64% of MSA patients reporting pain, sensory in 28%, dystonic in 21%,
      and levodopa-related in 16%, mostly related to off-period or diphasic dystonias.
      There was a mixed pain syndrome in 19% of these patients. Pain was significantly
      more commonly reported by females (P = 0.02), and by patients with levodopa
      induced dyskinesias (P = 0.02). No other clinical feature differentiated MSA
      patients who reported pain from those who did not. The mean delay between disease
      onset and onset of pain was 2.9 years, but pain was reported at the time of, or
      before, disease onset in about 30% of patients. The overall prevalence of pain in
      MSA was similar to that reported in IPD, but the distribution of pain categories
      was different.

PMID- 8750554
TI  - Bilateral suppression of the sympathetic nervous system in hemispheric brain
      infarction.
AB  - To assess sympathetic system function after hemispheric brain infarction rostral
      to the hypothalamus we investigated 24 patients with infarction in the territory
      of the middle cerebral artery. Anisocoria and basal lacrimal gland secretion were
      determined. The ninhydrin test was performed and the sympathetic skin response
      recorded in both hands and feet. The functions assessed by these tests were found
      to be reduced bilaterally. No significant lateralisation of the sympathetic
      nervous system could be demonstrated.

PMID- 8750555
TI  - Seizures at the onset of subarachnoid haemorrhage.
AB  - In a prospective study of 253 patients with subarachnoid haemorrhage, 16 (6.3%)
      had seizures at the onset of bleeding. None had a previous history of seizures.
      One was an alcoholic. None had metabolic imbalance. Hemiparesis, Hunt's grade >
      3, the amount of subarachnoid blood and the presence of an aneurysm were
      significantly more frequent in patients with seizures at the onset of
      subarachnoid haemorrhage. Although rebleeding and mortality or severe disability
      at discharge were more frequent in these patients, seizures were not a
      significant predictor of prognosis. One of the survivors with early seizures
      developed recurrent epileptic seizures 1 year later.

PMID- 8750556
TI  - Tumour necrosis factor alpha is elevated in serum and cerebrospinal fluid in
      multiple sclerosis and inflammatory neuropathies.
AB  - Tumour necrosis factor alpha (TNFalpha) is a peptide that is derived from T
      lymphocytes and macrophages and is used as a marker of activated cellular immune
      responses. TNFalpha was measured in paired sera and cerebrospinal fluid (CSF)
      from 30 patients with multiple sclerosis (MS) with worsening disability, 54
      patients with other neurological diseases, and 20 normal subjects. A sensitive
      enzyme-linked immunosorbent assay was used to determine the TNFalpha levels. We
      found significantly elevated serum and CSF levels in 12 (40%) and 6 (20%) MS
      patients, respectively, compared with healthy controls (P < 0.007 and P < 0.05).
      Among the 18 patients with neuropathy, we also found high serum and CSF TNFalpha
      values in 3 (17%) and 5 (28%) patients, respectively (P < 0.04 and P < 0.002).
      Our study shows that TNFalpha is probably involved in the pathogenetic mechanisms
      of MS and other inflammatory neurological diseases.

PMID- 8750557
TI  - Electrophysiological brainstem investigations in obstructive sleep apnoea
      syndrome.
AB  - Phasic inspiratory genioglossus activity prevents pharyngeal airway collapse in
      healthy subjects during sleep and is diminished or absent in obstructive sleep
      apnoea syndrome (OSAS), thus leading to pharyngeal obstruction. Case reports of
      OSAS after pontomedullary lesions indicate that impaired inspiratory genioglossal
      activity may result from brainstem lesions. We therefore investigated brainstem
      functions in 18 awake patients with OSAS using brainstem auditory evoked
      potentials, blink reflex, masseter reflex, masseter inhibitory reflex (in 11 of
      18 patients), magnetic evoked potentials of the tongue and electrooculography
      with vestibular testing. Fifteen of 18 patients showed no electrophysiological
      abnormalities. One patient had a left pontine and two patients a bilateral
      pontomesencephalic lesion, although a causal connection with OSAS was not
      conclusively confirmed. Our results do not support the assumption of a relevant
      structural brainstem lesion in OSAS patients with normal neurological findings.

PMID- 8750558
TI  - Neuropsychology of memory and SPECT in the diagnosis and staging of dementia of
      Alzheimer type.
AB  - We studied the role of neuropsychology and SPECT imaging in the diagnosis and
      staging of dementia of Alzheimer type (DAT) in 33 patients with mild disease and
      30 matched controls. Working, episodic, semantic and remote memory were assessed.
      For diagnosis, it was determined by logistic regression analysis that one of the
      memory tests (delayed verbal recall of the Doors and People Test) could correctly
      classify subjects as DAT or controls in 97% of cases. For staging, stepwise
      regression analysis using five of the memory tests could predict 70% of the
      variance in Mini Mental State Examination (MMSE) scores. The measures most useful
      for staging were tests of immediate recall, and tests of working, semantic and
      autobiographical memory. In a separate experiment, SPECT imaging on 31 of the
      above 33 patients and 24 different controls was used to address the issue of
      diagnosis and staging. 99Tc-HMPAO SPECT scans were analysed quantitatively to
      obtain measures of regional cerebral blood flow (rCBF). Logistic regression
      analysis showed that three of the SPECT regions of interest (left posterior
      temporal, right high frontal and right posterior temporal) could correctly
      classify subjects in 75% of cases. Of note was the fact that 39% of the DAT
      patients had normal SPECT scans. SPECT data were of limited use in modelling
      disease severity; only 38% of the variance in MMSE scores could be predicted from
      SPECT data. In addition, we found that the pattern of rCBF in DAT was much more
      heterogeneous than previously described.

PMID- 8750560
TI  - Are white matter lesions directly associated with cognitive impairment in
      patients with lacunar infarcts?
AB  - Forty-four patients (mean age 66, SD 8 years) with either clinical evidence of a
      focal lacunar syndrome (n = 36) or with disorders of memory or gait (n = 8) in
      the presence of a lacunar infarct on CT were studied for cognitive functioning
      and for the presence of white matter lesions on MRI. MR images were assessed by a
      neurologist and a neuroradiologist blinded to the clinical data. Thirty-six
      patients had one or more lacunar infarcts on CT or MRI (in the thalamus in 5, in
      the caudate nucleus in 3 and in the internal capsule or corona radiata in the
      remaining patients). Twelve patients had multiple infarcts. Severe lesions of the
      white matter were found in 13 patients, mild to moderate lesions in 20 patients.
      Scores on Digit Span, Digit Symbol and delayed recall of the 15-Words test were
      significantly lower in group with severe lesions, whilst there was a trend in the
      same direction for the Cognitive part of the Cambridge Examination of Mental
      Disorders in the Elderly, the Trailmaking B, Stroop colour interference test and
      the delayed visual reproduction of the Wechsler Memory Scale. These findings
      suggest that diffuse lesions of the white matter are an independent factor in the
      pathogenesis of intellectual dysfunction, also in patients with lacunar infarcts,
      but a truly independent analysis is difficult because the most severe involvement
      of the white matter tended to be associated with the largest number of lacunar
      infarcts.

PMID- 8750559
TI  - Acute infectious disorders of the spinal cord and its roots with gadolinium-DTPA
      enhancement in magnetic resonance imaging.
AB  - We studied three patients with myelomeningoradiculitis caused by Borrelia
      burgdorferi, herpes zoster virus or cytomegalovirus infection. All patients
      underwent MRI of the spinal cord with gadolinium-DTPA and showed enhancing
      lesions of the spinal cord or nerve roots that correlated with clinical signs.
      Gadolinium-DTPA enhancement may visualize lesions that suggest an inflammation
      associated with blood-brain-barrier alteration and indicate the diagnosis before
      serological results are available.

PMID- 8750561
TI  - Bedside screening for aphasia: a comparison of two methods.
AB  - A prospective study was carried out in 50 consecutive patients referred with
      suspected aphasia in order to compare the Frenchay Aphasia Screening Test (FAST)
      with the Sheffield Screening Test for Acquired Language Disorders (SST). The
      study included 32 men and 18 women with a mean (SEM) age 53.9 (2) years. The
      comprehension scores on the FAST were correlated with receptive skills on the SST
      r = 0.74 (P < 0.001). For expression, the correlation coefficient was r = 0.92 (P
      < 0.001) and the total scores of the two tests correlated closely r = 0.89 (P <
      0.001). There was a positive correlation between total score on the FAST and the
      Short Orientation, Memory and Concentration test (SOMC) r = 0.86 (P < 0.001), and
      the total scores on the SST and SOMC r = 0.91 (P < 0.001). The Barthel index also
      correlated positively with the FAST r = 0.59 (P < 0.001) and SST r = 0.63 (P <
      0.001). The study demonstrated that the two tests are simple, short and similar
      in their predictive value for the screening and diagnosis of aphasia. The SST was
      found to have additional advantages, as it does not require any special equipment
      or stimulus cards, and it was not affected by visual neglect.

PMID- 8750562
TI  - Intravascular malignant lymphomatosis with neurological symptoms.

PMID- 8750563
TI  - Sulfonylurea receptors and mechanism of sulfonylurea action.
AB  - Binding of hypoglycemic sulfonylureas and their analogues to the sulfonylurea
      receptor in the beta-cell plasma membrane mediates closure of the ATP-sensitive
      K+-channel (KATP-channel) and thereby stimulation of insulin release. The
      sulfonylurea receptor is a member of the traffic ATPase family with two
      intracellular nucleotide binding folds. The receptor binding site for
      hypoglycemic drugs is located at the cytoplasmic face of the plasma membrane.
      Mutations in the sulfonylurea receptor gene have been detected which cause
      familial hyper-insulinism. Non-beta-cell sulfonylurea receptors do not contribute
      to the therapeutic benefit of sulfonylureas, but might be involved in presumed
      adverse effects of sulfonylureas in the cardiovascular and the central nervous
      system.

PMID- 8750564
TI  - Functional diversity of the pineal hormone melatonin: its role as an antioxidant.

PMID- 8750565
TI  - Diabetes: many leads to PKC (protein kinase C)

PMID- 8750566
TI  - Insulin leads to a parallel translocation of PI-3-kinase and protein kinase C
      zeta.
AB  - Protein kinase C consists of a family of at least 12 isoforms which exhibit clear
      differences in their cofactor dependence and responsiveness to phospholipids.
      Insulin effects on PKC translocation/activation are now clearly established but
      responsiveness to this hormone was observed so far only for the classical PKC
      isoforms alpha and beta. While activation of the classical PKC's requires Ca2+
      and occurs mainly through Diacylglycerol (DAG), stimulation of the atypical
      isoform PKC-zeta appears to function through a different mechanism involving PI-3
      kinase activation. In the present study we used rat-1 fibroblasts stably over
      expressing human insulin receptor to investigate whether insulin can activate PKC
      zeta and whether such an effect might be related to insulin's effect on PI-3
      kinase. After stimulation of the cells with insulin (10(-7) mol/l) for one to ten
      minutes, a rapid translocation of PKC-zeta to the plasma membrane was detectable,
      as determined by immunoblotting of plasma membrane proteins with antibodies
      against PKC-zeta. In parallel immunoblots applying antibodies against the
      regulatory subunit of PI-3-kinase (p85), an insulin-induced translocation of p85
      was detectable within one minute after stimulation. The translocation of p85 was
      associated with an increase in PI-3-kinase activity at the plasma membrane. The
      data show that insulin stimulates translocation of PKC-zeta in rat-1 fibroblasts.
      The parallel kinetics of PI-3-kinase translocation/activation and PKC-zeta
      translocation are compatible with the idea that the insulin effect on PKC-zeta is
      transduced through PI-3-kinase activation.

PMID- 8750567
TI  - Intensive insulin therapy with insulin lispro in patients with type 1 diabetes
      reduces the frequency of hypoglycemic episodes.
AB  - In a randomized, open-label, controlled cross-over trial, 107 patients with type
      1 diabetes were treated with either regular human insulin or insulin lispro, a
      rapid-acting insulin analogue. After a lead-in period of 2 to 4 weeks, the
      patients were randomized to receive intensified insulin treatment with one of the
      insulins. NPH-human insulin was used for basal substitution in both groups. The
      crossover took place after 3 months of treatment. Efficacy and safety of the
      drugs were established by the assessment of hemoglobin A1c, pretest blood
      glucose, 1 and 2-hour postprandial glucose excursions, number of hypoglycemic
      episodes, daily insulin doses, body weight, insulin antibodies, and the number
      and severity of adverse events. A questionnaire comprised of four primary domains
      was used to measure some quality of life aspects of the patients. Both treatment
      regimens were well tolerated. While no differences were seen in the hemoglobin
      A1c values, there was a trend for a decrease in the pretest blood glucose levels
      and significant decreases of the 1 and 2-hour postprandial glucose excursions in
      the patients treated with insulin lispro. The number of hypoglycemic episodes was
      also significantly lower in the insulin lispro treatment period. The evaluation
      of the quality of life questionnaire revealed an improvement in the patients
      treatment satisfaction for the insulin lispro group. During treatment with
      insulin lispro, the basal insulin doses increased slightly. However, the total
      daily insulin doses decreased to a greater extent with insulin lispro as compared
      to regular human insulin. Human insulin-specific antibody binding values at
      endpoint were not different for the two treatments. In conclusion, intensive
      insulin treatment with insulin lispro therapy results in improved postprandial
      glycemic control and HbA1c levels at least equal to the treatment with regular
      human insulin but with less hypoglycemia and more treatment satisfaction for the
      patient.

PMID- 8750568
TI  - Heterogeneity of hypothalamic-pituitary-adrenal system response to a combined
      dexamethasone-CRH test in multiple sclerosis.
AB  - The endocrine system participates in the regulation of the immune and neural
      systems and therefore hormonal factors probably play an important role in the
      development and course of multiple sclerosis (MS). Specifically, the hypothalamic
      pituitary-adrenal (HPA) system seems crucial because (a) the inflammatory
      response is accompanied by HPA activation; (b) animal models with an inherited
      HPA defect are prone to developing experimental autoimmune encephalitis; and (c)
      most important, corticosteroids are still the most widely used treatment. We
      administered a recently developed neuroendocrine function test that combines
      dexamethasone suppression (1.5 mg orally at 2300 h) and corticotropin-releasing
      hormone (CRH) stimulation (100 micrograms i.v. at 1500 h the following day) and
      measured the response of plasma cortisol and corticotrophin (ACTH) secretion in
      19 patients with an acute exacerbation of MS. These patients had a significantly
      higher mean plasma cortisol response than age-matched controls (peak minus
      baseline; 48.1 +/- 10.5 ng/ml [mean +/- SEM] versus 19.8 +/- 4.2 ng/ml; p <
      0.05), but the corresponding ACTH values for the two groups were
      indistinguishable (13.4 +/- 1.4 pg/ml [mean +/- SEM] versus 11.3 +/- 1.4 pg/ml;
      n.s.). The response range in the patients was broader and we identified six
      patients with excessive cortisol release (peak minus baseline: 100.5 +/- 14.4
      ng/ml [mean +/- SEM]), whereas four patients failed to respond at all. The
      hormonal response patterns were not related to previous treatments with
      corticosteroids or other immunosuppressants or to psychopathological features.
      These results point to a heterogeneity of HPA system function, most likely at the
      corticosteroid receptor level, which has clinical implications for all those
      treatments that affect the HPA system and the course of MS.

PMID- 8750569
TI  - The effect of diltiazem on the manifestations of hyperthyroidism and thyroid
      function tests.
AB  - The aim of this study is to evaluate the effect of diltiazem on the symptoms and
      signs of hyperthyroidism and thyroid function tests and to assess whether
      diltiazem can be used associated with an anti-thyroid drug, propylthiouracil.
      Twenty-two patients with hyperthyroidism were included in a prospective,
      randomized and placebo controlled study. Group 1 (n:12) patients received
      diltiazem, 60 mg twice a day, for 30 days. Group 2 (n:10) patients received
      placebo for 30 days. The patients in both groups were given propylthiouracil, 100
      mg three times a day, for the last 20 days of the study period. The patients
      remained in the hospital during the first 10 days. A standardized hyperthyroid
      symptom score (HSS) and thyroid function tests including thyroid-stimulating
      hormone (TSH), free thyroxine (free T4), free triiodothyronine (free T3), total
      thyroxine (T4) and total triiodothyronine (T3) were evaluated before and after 10
      and 30 days of the study period. HSS decreased from 27.80 +/- 4.54 to 22.51 +/-
      4.04 after 10 days of diltiazem therapy in Group 1 (p < 0.01). But there was no
      change in HSS in Group 2 (p > 0.01). No significant changes in thyroid function
      tests have occurred in both groups after 10 days of treatment. Diltiazem can be
      used in patients with hyperthyroidism to alleviate adrenergic manifestations. It
      can also be safely combined with propylthiouracil.

PMID- 8750570
TI  - Norepinephrine induced calcitonin secretion in rat medullary thyroid carcinoma 6
      23 cells: interaction between intracellular calcium and cAMP.
AB  - Catecholamines are known to stimulate calcitonin secretion in C-cells by a
      receptor mediated pathway, but details regarding the postreceptor events are
      unknown. Since norepinephrine (NE) influences intracellular calcium concentration
      [Ca2+]i and cAMP levels in C-cells, we used different adrenergic agonists and
      antagonists to investigate the effect of NE on [Ca2+]i and cAMP accumulation, and
      on calcitonin secretion in rat MTC-6-23 cells. NE stimulated intracellular cAMP
      accumulation and calcitonin secretion dose-dependent, with 10(-7) mol/l causing
      maximal stimulation. The NE induced increase in cAMP accumulation/calcitonin
      secretion could be decreased to baseline by equimolar amounts of the beta
      adrenergic blocker propanolol. The alpha-blocker phentolamine did not
      significantly influence NE stimulated calcitonin secretion even at high
      concentrations. The beta-adrenergic agonist fenoterol proved to be as effective
      as NE in stimulating cAMP accumulation/calcitonin secretion. Activation of
      inhibitory G-proteins by the adenosine A1 receptor analogue N6
      phenylisopropyladenosine at 10(-6) mol/l completely blocked NE stimulated
      calcitonin secretion. NE stimulated calcitonin secretion was also completely
      blocked by the cAMP antagonist RpcAMPs. The calcium channel blocker verapamil
      significantly inhibited NE stimulated calcitonin secretion, but interestingly
      increased NE stimulated cAMP accumulation. We conclude that NE induced calcitonin
      secretion is mediated through beta-receptors coupled to adenylate cyclase via G
      proteins. cAMP and changes in [Ca2+]i are necessary for NE induced calcitonin
      secretion. There seems to be a complex interaction between the two pathways even
      regarding events occurring distal to cell membrane.

PMID- 8750571
TI  - Different immunophenotype and autoantibody production by peripheral blood and
      thyroid-derived lymphocytes in patients with Graves' disease.
AB  - Direct multi-colour flow cytometric analysis was employed in patients with
      Graves' disease (n = 10) to determine the immunophenotype in peripheral blood
      lymphocytes (PBL) at the time of diagnosis without treatment (PBLw) and prior to
      operation (PBLp) and in thyroid-derived lymphocytes (TL). Additionally, the
      secretion of anti-thyroperoxidase antibodies (anti-TPO) was measured during
      culture of isolated peripheral or thyroid-derived B cells. Among TL from patients
      with high serum levels of anti-TPO (6/10) a significantly (p < 0.01) higher
      percentage of B cells were detected compared to PBLp (TL: 21.7 +/- 7.2%; PBLp:
      13.2 +/- 4.5%). Enriched thyroid-derived B cells only from these patients also
      showed high spontaneous anti-TPO secretion during culture. The difference between
      peripheral and thyroid-derived natural killer (NK) cells was highly significant
      (p < 0.001; TL: 5.6 +/- 6.3%; PBLp: 13.6 +/- 5.5%). Two patients were found with
      a higher number of NK cells within TL. These patients were among those who had a
      low number of B cells infiltrating the thyroid gland. Regarding the expression of
      several other differentiation antigens, i.e. CD4 and CD8, gamma/delta TCR bearing
      T cells and CD45R0 on CD4+ T cells as a marker for memory cells, on TL no
      differences could be detected between patients with or without anti-TPO. In TL
      31.5 +/- 7.7% of CD3- cells expressed the HLA-DR antigen (vs. 6.1 +/- 2.4% in
      PBLp; p < 0.001). Half of these cells simultaneously expressed the activation
      antigen CD69. Surprisingly, the number of CD3+ TL bearing the IL-2 receptor
      (CD25) and transferrin receptor (CD71) was not increased. Taken together, the
      proportional distribution of B and NK cells within the thyroid correlates with
      the anti-TPO secretion in vivo and in vitro, suggesting different immune response
      regulation processes of TL.

PMID- 8750572
TI  - The long-term effect of low protein diet on the somatostatin hypothalamic
      neuronal system and the pituitary growth hormone cells in growing ewe.
AB  - Three-month old Polish Lowland female lambs were fed isocaloric diets containing
      14.2% (standard) or 8.1% of proteins for twenty weeks. Changes in body weight
      were characteristic for normal growth performance in all animals, but daily body
      gain calculated for the whole experimental period was significantly lower in
      lambs fed a low protein diet (87.9 +/- 13.5 and 158 +/- 13.8 g/day,
      respectively). Two series of blood collections (4 hrs with 15 min interval) were
      performed at age of 21 and 26 weeks in order to analyze the growth hormone (GH)
      concentration in the peripheral blood. The results obtained by radioimmunoassay
      showed that at both ages the mean concentration of GH was significantly higher in
      the group fed a low protein diet (4.84 +/- 2.23 and 3.68 +/- 1.86 vs 1.46 +/-
      0.72 and 1.48 +/- 0.44 ng/ml, respectively) and this difference was associated
      with significant elevation of the pulse amplitude (3.83 +/- 4.23 and 4.54 +/-
      3.06 vs 1.48 +/- 1.11 and 1.31 +/- 0.68 ng/ml, respectively). Using
      immunocytochemistry, the somatostatin in the hypothalamus and the GH in the
      pituitary cells were analyzed in all animals slaughtered at age of 8 months.
      Lowering the content of dietary proteins diminished markedly the content of
      immunoreactive somatostatin in the median eminence (ME) and augmented the
      concentrations of the immunoproduct in the somatostatin perikarya. In the
      pituitary gland, a marked increase of the number of GH-producing cells was
      observed. The results obtained indicate that chronic restriction of dietary
      proteins, irrespective of sufficient energy supply, augment the secretion of GH
      via a decrease in the hypothalamic somatostatin output due to the suppression of
      its axonal transport.

PMID- 8750573
TI  - Naloxone influence on the growth hormone, prolactin and thyrotropin response to
      thyrotropin releasing hormone in acromegalic patients.
AB  - In order to gain insight into the neuroendocrine mechanism underlying the
      paradoxical GH response to TRH in acromegalic patients, we have investigated the
      effect of an infusion of Naloxone (Nal, 1.6 mg/hr for two hours), on a TRH test
      performed both in responder (n = 9) and non-responder (n = 5) acromegalic
      patients. The response of GH, PRL and TSH to TRH injection were evaluated. NAL
      did not exert significant variations in the GH response, even if different
      patterns of GH response during NAL were observed in the group of TRH-responder
      patients. Similarly, TRH-induced PRL response was not significantly affected by
      the infusion of an opiate antagonist. On the contrary, a significant inhibition
      of the TSH response was observed in the group of TRH-responder patients (delta
      TSH after TRH 4.76 +/- 1.11 microU/ml, after NAL + TRH 2.81 +/- 0.99 microU/ml, p
      < 0.05). No significant effects were observed in the TRH non-responder patients
      (delta TSH after TRH 4.58 +/- 1.44 microU/ml, after NAL + TRH 6.26 +/- 3.27
      microU/ml). The differences observed in the two groups of patients could be
      ascribed to a different endogenous somatostatinergic tone and could furnish a
      prognostic indication in acromegalic patients.

PMID- 8750574
TI  - Luteinizing hormone pulse frequency is increased by arginine infusion in
      prepubertal sheep.
AB  - Puberty in sheep is initiated by a complex neuroendocrine interplay which
      cascades into an increased LH pulsatility at this time. Blood-borne amino acids
      have been proposed as metabolic signals for the stimulation of GnRH/LH secretion,
      a mandatory requirement for pubertal onset. In previous experiments we have
      demonstrated that a 1 h infusion of L-arginine (ARG) was capable of stimulating
      the LH secretion in prepubertal ewes. The aim of the present study was to further
      examine the effect of an intravenous infusion of ARG on LH secretion. Prepubertal
      ewes were infused for 6 h with 15 (Group ARG15, n = 5) or 30 g (Group ARG30, n =
      5) of L-ARG dissolved in 500 mL saline (pH 7.4), while saline was administered as
      control (Group S, n = 5). Since ARG is metabolized to ornithine (ORN), equimolar
      doses of L-ORN were additionally tested (Group ORN12 and ORN24, n = 5,
      respectively). Blood samples were obtained at 15 minute intervals during and
      after experimental infusions to characterize the LH pulsatile secretion. The
      resulting hormone data arrays were searched for significant fluctuations by the
      PULSAR program. The LH pulse frequency was found to be higher in groups of ARG
      treated than in saline or ORN infused sheep during the 6-h infusion period: 5.6
      +/- 1.0 (ARG15) vs. 5.0 +/- 0.5 (ARG30) vs. 2.0 +/- 0.9 (S, p < 0.01) vs. 3.4 +/-
      0.9 (ORN12) vs. 3.4 +/- 0.9 pulses/6 h (ORN24, p < 0.05). The total number of
      pulses was higher in ARG infused lambs than in saline or ORN infused animals:
      11.2 +/- 1.2 (ARG15) vs. 10 +/- 1.1 (ARG30) vs. 13.8 +/- 1.4 (S) vs. 5.8 +/- 1.7
      (ORN12) vs. 5.8 +/- 2.0 pulses/12h (ORN24), respectively. The LH mean secretion
      was comparable during both 6-h periods in all groups. Results of our experiments
      demonstrate increased LH pulse frequencies during ARG infusions, suggesting an
      action of ARG to stimulate hypothalamic GnRH release. Thus, ARG may be a critical
      determinant for enhanced LH pulsatility as a prerequirement for the onset of
      puberty in the sheep.

PMID- 8750575
TI  - Human follicular fluid levels of endothelins in relation to oocyte maturity
      status.
AB  - The levels of endothelins 1 and 2 (ET-1 and ET-2) have been examined in 415
      follicular fluids of 57 women participating in the IVF-ET programme in the
      University Women's Hospital, Marburg, in relation to the morphological appearance
      ("maturity") and fertilizability of harvested oocytes as well as to the levels of
      inhibin, FSH, IGF-1, estradiol and progesterone. Follicular aspiration was done
      transvaginally in all patients after down regulation with nafareline and ovarian
      stimulation using urofollitropin and menotropin. Ovulation was induced by hCG.
      ETs were measured by RIA using commercial kits supplied by Peninsula
      Laboratories, Belmont, CA. For FF samples, ET-1 and ET-2 RIAs were revalidated.
      Immunoreactive ET-1 was detectable in all follicular samples, the average level
      being 18.5 +/- 11.8 pg/ml, ET-2 was present only in 67.5% of the samples, the
      average level being 13.6 +/- 16.3 pg/ml. There was no significant difference in
      the average levels of ET-1 in the fluids of small, medium and large follicles.
      However, there was a significantly higher level of ET-2 in the fluids of medium
      compared to large follicles and there was a negative correlation of the ET-2
      levels to the volume of the follicle (p < 0.01) which suggests that ET-2 could
      play a role during the maturation of the ovarian follicles. Unlike ET-1, the mean
      concentrations of ET-2 were significantly higher in the fluids with oocytes which
      could be fertilized and cleaved than in those with oocytes which did not
      fertilize or cleave, thus indicating a role for ET-2 in the process of oocyte
      maturation. No correlations of ET levels were found with the levels of inhibin,
      FSH, estradiol and progesterone. However, ET-2 levels significantly correlated
      with the levels of IGF-1 (p < 0.001) indicating a possible synergistic effect of
      endothelins and IGF-system. In conclusion, this study is further evidence for a
      physiological role of the ETs in the human ovary.

PMID- 8750576
TI  - Decreased secretion of gonadotropins in a patient with Graves' disease.
AB  - A 56-year-old female with Graves' disease who presented with decreased secretion
      of gonadotropins is described. She was admitted to hospital because of her being
      in a state of confusion. One month before admission she had been diagnosed as
      having Graves' disease and was treated with methimazole since then. Plasma LH and
      FSH levels were undetectable, and their responses to LH-RH were extremely
      decreased in spite of undetectable levels of plasma estradiol and estriol. One
      year after treatment, both basal and stimulated values of LH and FSH reverted to
      normal as did those of TSH. Reversible suppression of gonadotropins as described
      herein has never been reported in cases of Graves' disease.

PMID- 8750577
TI  - Epstein-Barr virus serology in patients with autoimmune thyroiditis.
AB  - Elevated titers of antibodies against different antigens of Epstein-Barr virus
      (EBV) are found in some immunodeficient states, malignancies or in autoimmune
      disorders. We examined EBV serology in the group of 22 patients with autoimmune
      thyroiditis as compared with the group of 35 healthy volunteers. Titers of
      antibodies against viral capsid antigen (IgG-VCA) were more often found in the
      group of patients than in the control group (p = 0.000 35 for younger than 40
      years and p = 0.00115 for older than 40 years) and the positivity of antibodies
      against early antigen (IgG-EA-D/DR) was also significantly more often found in
      the group of patients (p = 0.0031 and p = 0.0019 respectively) than in the
      control group.

PMID- 8750579
TI  - Indications for hepatic ultrasonography in breast cancer staging and follow-up.
AB  - Retrospective analysis of the medical records of 6649 breast cancer patients seen
      over an 11-year period found 438 patients (6.6%) with liver metastases (LM) and
      432 patients (6.5%) with benign liver lesions (BLL). Liver ultrasonography (LUS)
      and liver function tests had been performed for all patients. LM were the first
      manifestation of metastatic spread in 20.1% of the 438 patients; median survival
      was related to the presence (6.7 mo.) or absence (12.2 mo.) of extrahepatic
      metastases (EHM). Liver function tests were normal in 20.5% of the patients in
      whom LM were first diagnosed by LUS. Most LM were hypoechoic (70.9%) BLL
      corresponded to cysts, hemangiomas, calcifications, and focal fatty infiltration.
      LUS appears indicated for (i) pretherapy disease staging, and in particular for
      detection of BLL, and (ii) follow-up of patients without EHM for early diagnosis
      of LM.

PMID- 8750578
TI  - Correlation of growth fraction by Ki-67 and proliferating cell nuclear antigen
      (PCNA) immunohistochemistry with histopathological parameters and prognosis in
      primary breast carcinomas.
AB  - The immunoreactivity for Ki-67 and PCNA was investigated in 487 patients with
      primary breast carcinomas using MIB-1 (Immunotech, France) and PC-10 (DAKO,
      Denmark) as primary antibodies. Formalin-fixed and paraffin-embedded tissue
      sections were used. The immunoreactivity for Ki-67 and PCNA was found to be
      independent of the length of fixation if the sections were pretreated in a
      microwave oven in citrate buffer and distilled water, respectively. The
      immunostaining was evaluated semiquantitatively. High Ki-67 score (more than 1%
      positive tumour cells) and PCNA over-expression (more than 25% positive tumour
      cells) were correlated with clinicopathological parameters such as large tumour
      size, high histological grade (poor differentiation), and absence of steroid
      hormone receptors, which are parameters of an aggressive phenotype of the tumour.
      In univariate analysis of survival data, both Ki-67 and PCNA were parameters of a
      poor overall survival in both lymph node-positive and -negative patients. In
      multivariate anlaysis using a Cox model stratified by nodal status, Ki-67 and
      PCNA failed to be of prognostic significance whereas classical histopathological
      parameters such as tumour size and histological grade turned out to be of
      independent prognostic significance in both lymph node-positive and -negative
      patients, while progesterone receptors were of independent prognostic
      significance only in lymph node-positive patients.

PMID- 8750581
TI  - Predicting axillary lymph node metastases in breast carcinoma patients.
AB  - Routine axillary dissection is primarily used as a means of assessing prognosis
      to establish appropriate treatment plans for patients with primary breast
      carcinoma. However, axillary dissection offers no therapeutic benefit to node
      negative patients and patients may incur unnecessary morbidity, including mild to
      severe impairment of arm motion and lymphedema, as a result. This paper outlines
      a method of evaluating the probability of harbouring lymph node metastases at the
      time of initial surgery by assessment of tumour based parameters, in order to
      provide an objective basis for further selection of patients for treatment or
      investigation. The novel aspect of this study is the use of Maximum Entropy
      Estimation (MEE) to construct probabilistic models of the relationship between
      the risk factors and the outcome. Two hundred and seventeen patients with
      invasive breast carcinoma were studied. Surgical treatment included axillary
      clearance in all cases, so that the pathologic status of the nodes was known.
      Tumour size was found to be significantly correlated (P < 0.001) to the axillary
      lymph node status in the multivariate anlaysis with age (P = 0.089) and vascular
      invasion (P = 0.08) marginally correlated. Using the multivariate model
      constructed, 38 patients were predicted to have risk of nodal metastases lower
      than 20%, of these only 4 (10%) patients had lymph node metastases. A comparison
      with the Multivariate Logistic Regression (MLR) was carried out. It was found
      that the predictive quality of the MEE model was better than that of the MLR
      model. In view of the small sample size, further verification of this model is
      required in assessing its practical application to a larger population.

PMID- 8750580
TI  - Lack of prognostic significance of the monoclonal antibody Ki-S1, a novel marker
      of proliferative activity, in node-negative breast carcinoma.
AB  - In a series of 205 node-negative breast cancers (NNBC), we determined staining by
      the novel antibody Ki-S1, a marker of tumor cell proliferation, in order to test
      its association with other prognostic variables and its prognostic significance.
      Ki-S1 was determined in routinely formalin-fixed paraffin-embedded tumor samples.
      Ki-S1 gave a nuclear staining in the majority of the carcinomas (188 of 205),
      with percentages of reacting nuclei ranging from 2% to 90% (median value of 7%).
      In 107 tumors frozen sections were available to also assess the Ki-67 antibody.
      Among these, 94 had a nuclear staining of cancer cells ranging from 5% to 80%
      (median value of 7%). In 46 tumors we also determined the MIB-1 antibody. The
      percentage of MIB-1 nuclear staining ranged from 1% to 50% (median value of 20%).
      There was no significant relationship between Ki-S1 and the other two cell
      kinetic markers. Ki-S1 labeling was significantly associated only with tumor size
      (p = 0.03). With a median follow-up of 6 years, Ki-S1 had no significant
      prognostic value for either relapse-free survival (RFS) or overall survival (OS)
      (Ki-S1 as continuous logarithmic variable; p = 0.86 and p = 0.23, respectively).
      For RFS the following variables had a significant prognostic value: Ki-67 (< or =
      10% vs > 10%; p = 0.037); progesterone receptor (PgR) expression (- vs+/++; p =
      0.041); tumor size (pT1 vs pT2-3; p = 0.042) and grading (GI vs GII-III; p =
      0.047). For OS, tumor size (p = 0.0044), age (continuous variable; p = 0.0060),
      and Ki-67 (p = 0.043) were significantly prognostic. In multivariate analysis
      (final model), only tumor size retained a significant and independent prognostic
      value for RFS (p = 0.0042). For OS, both tumor size (p = 0.0029) and age (< or =
      55 years vs > 55 years; p = 0.041) retained significance in the multivariate
      model. In conclusion, Ki-S1 does not seem to have prognostic relevance in this
      series of NNBC. Possible hypotheses to explain this observation are discussed.

PMID- 8750582
TI  - Expression and localization of inhibin/activin subunits and activin receptors in
      MCF-7 cells, a human breast cancer cell line.
AB  - Inhibins and activins are members of the transforming growth factor-beta (TGF
      beta) superfamily. Since TGF beta has been shown to be a potent proliferation
      inhibiting agent for the breast cancer cell line MCF-7, we determined whether
      this cell line (a) transcribes messenger RNAs coding inhibin/activin alpha-, beta
      A-, and beta B-subunits and activin receptors, and (b) produces inhibin and/or
      activin proteins. Messenger RNAs for alpha- and beta-subunits of inhibin/activin
      and activin receptor II in MCF-7 cells were detected and localized using the
      reverse transcription-polymerase chain reaction (RT-PCR) analysis and in situ
      hybridization, respectively. The identity of the RT-PCR products was confirmed by
      DNA sequencing of PCR products. Immunocytochemically, inhibin and activin were
      localized in these cells. Our findings that messenger RNAs encoding inhibin alpha
      subunit, inhibin/activin beta A-subunit, and activin receptor II were expressed,
      and inhibin/activin proteins were produced by MCF-7 cells, imply that these
      gonadal growth factors may have paracrine/autocrine functions in human breast
      cancer. Further, these observations suggest that these growth factors may be
      involved in regulating the growth and differentiation of human breast cancer
      cells.

PMID- 8750583
TI  - Elemental composition of bone minerals in women with breast cancer treated with
      adjuvant tamoxifen.
AB  - Oestrogen levels play a major role in conditioning the rates of bone changes in
      women. Tamoxifen is a synthetic oestrogen antagonist commonly used as an adjuvant
      therapy for breast cancer. The goal of the present study was to study the amount
      and the elemental composition of bone minerals in the appedicular skeleton of
      women with breast cancer treated with adjuvant tamoxifen, as well as to
      investigate the possibility of increased risk for osteoporosis. Forty-two
      patients, aged 41-65 years, without skeletal metastases were studied. The mean
      duration of tamoxifen administration on a daily dose of 20 mg was 21 months
      (range 1-59 months). It was found that neither the amount of phosphorus in hands
      (HBP) nor forearm bone mineral content (BMC) differ statistically from those of
      age-matched healthy subjects. This was confirmed by reassessing bone mineral
      status after 30 months in 17 postmenopausal patients treated with tamoxifen for a
      mean time of 52 months. In conclusion, our data support that long-term tamoxifen
      treatment has no adverse or protective effect on the amount and elemental
      composition of the appedicular skeleton.

PMID- 8750584
TI  - The luteal heat cycle of the breast in disease.
AB  - Wearing a special thermometric brassiere, selected women self-measured their
      breast surface temperature. These measurements were made during one hour each
      evening at home for one menstrual cycle under standard conditions of overclothing
      and room temperature. To stage their cycle they also collected daily samples of
      saliva in their freezer for immuno-assay of progesterone concentration in the
      laboratory. A total of 82 women participated, most having young families. This
      total included four groups, a control group (N = 25) and three 'disease' groups,
      namely: family history of breast cancer (14); benign breast disease (12); and a
      'cancer-associated' group (31) who had had previous cancer surgery. A significant
      breast temperature rhythm with a period at or about 28 days was found not only in
      the controls but also in the three groups of breasts designated 'disease'.
      Nevertheless, consistent rhythm abnormalities were found in all the disease
      groups. Most evident was a hyperthermia throughout the cycle, a reduction in the
      rhythm amplitude, and a tendency for the breast temperature rhythm to be manifest
      1-2 days earlier in the menstrual cycle.

PMID- 8750585
TI  - Abnormal expression of MDM-2 in breast carcinomas.
AB  - MDM-2 is a cellular oncoprotein that binds to the p53 protein and abrogates its
      growth-suppressing function. At least seven MDM-2 mRNAs and five proteins (p90,
      p85, p76, p74, and p57) have been reported in tissue culture. MDM-2 gene
      amplification occurs in human sarcomas and high-grade gliomas. MDM-2
      overexpression without gene amplification has been reported in leukemias and
      lymphomas. Here we report MDM-2 mRNA overexpression in 24 (73%) out of 33 cases
      of human breast carcinoma as compared with normal breast tissue. The MDM-2
      overexpression was seen in the absence of MDM-2 gene amplification. MDM-2 protein
      expression was studied by western blot analysis in 21 of these cases of
      carcinoma. We found complete concordance between MDM-2 mRNA overexpression and
      MDM-2 protein levels. MDM-2 proteins were overexpressed in 15 of 21 breast
      carcinoma tissue samples but not in normal breast tissue controls. Ten of these
      fifteen cases overexpressed MDM-2 p57 protein, two cases overexpressed both p57
      and p90, and three cases overexpressed only p90. MDM-2 overexpression was
      confirmed by immunohistochemistry. p53 overexpression was also studied by
      immunohistochemistry, 69% of breast carcinomas that overexpressed the MDM-2 mRNA
      had detectable nuclear p53 protein. These findings demonstrate that MDM-2
      oncoprotein expression is altered in primary human breast carcinomas at both mRNA
      and protein levels. In addition, our results suggest that MDM-2 p57 protein
      represents the main MDM-2 protein altered in breast carcinomas.

PMID- 8750586
TI  - Activities of adenosine deaminase, 5'-nucleotidase, guanase, and cytidine
      deaminase enzymes in cancerous and non-cancerous human breast tissues.
AB  - We measured activities of some DNA turnover enzymes in 9 breast tissues with
      stage II cancer, 6 breast tissues with stage IIIa cancer, and 9 non-cancerous
      adjacent breast tissues from the same patients with stage II cancer. We found
      higher Adenosine Deaminase (ADA) and 5'-Nucleotidase (5'NT) and lower Guanase
      (GUA) activities in the cancerous tissues compared with the non-cancerous ones.
      No meaningful differences were however found between Cytidine Deaminase (CD)
      activities. Regarding the correlation analysis, positive correlations were
      established between ADA and 5'NT activities of the cancerous tissues (r = 0.45
      for the tissues with stage II and r = 0.60 for the tissues with stage IIIa
      cancer). No meaningful correlations were however found between other enzyme
      activities. Relating to activity ratios, no meaningful differences were found
      between ADA/5'NT values in the tissues. GUA/CD ratios were however lower and the
      other ratios higher in the cancerous tissues. Results indicated that ADA and 5'NT
      activities increased and GUA activity decreased in the cancerous breast tissues
      but CD activities did not change in the tissues affected. It has been suggested
      that increased ADA and 5'NT together with decreased GUA activities might be a
      physiologic attempt of the cancer cells to provide more substrates needed by
      cancer cells to accelerate the salvage pathway activity. Furthermore, high ADA
      activity might also play part in the detoxication process of high amounts of
      toxic adenosine and deoxyadenosine substrates produced from accelerated purine
      metabolism in the cancerous tissues.

PMID- 8750587
TI  - Managed care: "new moves," moral uncertainty, and a radical attitude.

PMID- 8750588
TI  - Comments on the AMA report "Ethical issues in managed care".

PMID- 8750589
TI  - Interests, obligations, and justice: some notes toward an ethic of managed care.
AB  - In their commentary on the recent report on the ethics of managed care by the
      American Medical Association's (AMA) Council on Ethical and Judicial Affairs,
      Miles and Koepp offer two salient criticisms: For one thing, they fault the
      Council for not disclosing how intellectual, legal, and financial conflicts of
      interest may have influenced the Council's ethical opinions. Specifically, they
      point to the AMA's customary interest in preserving the fee-for-service system
      and in avoiding potential litigation that might arise from strictures imposed on
      rulings of the Council on Ethical and Judicial Affairs by the Federal Trade
      Commission (FTC). For another, Miles and Koepp decry the Council's focus on the
      ethical obligations of individual physicians to their own patients to the neglect
      of their obligations to the healthcare plan, the other patients in the plan, and
      to society at large. Specifically, they lament the lack of a well-developed ethic
      of distributive justice and collective governance suitable to the economic
      exigencies of allocating resources. In this commentary, I wish to examine more
      closely two issues raised by Miles and Koepp's critique. The first issue is the
      assumption that the existence of interests--and, therefore, the possibility of
      conflicts of interest--is relevant in assigning validity to the conclusions of an
      ethical deliberation and that full disclosure is helpful in determining that
      validity. The second issue is the proper ethical relationship that should obtain
      between the obligations of physicians, to their own patients with whom they have
      a covenant of trust, and the obligations they incur to a health plan or to
      society when they sign a contract as a participating physician. This is part of
      the more general question of the proper relationship between commutative and
      distributive justice when they are in conflict. A third issue, which neither
      Miles and Koepp nor I address is the ethical propriety or moral legitimacy of
      restraints imposed by the FTC on the ethical guidelines of a profession. Should
      the FTC's legal hegemony over competition overrule the integrity of professional
      ethics? Should it make any difference in the Council's ethical opinions? This is
      a subject for more extended treatment than I can give it here. Suffice it to say
      that the rulings of the FTC are legal, not ethical, rulings. As such, their
      validity must be subjected to the same critical examination as other ethical
      statements. The mere existence of an FTC ruling, its practical consequences
      notwithstanding, is no warrant for abandoning an ethical principle. This is
      particularly the case since the FTC has made the protection of competition its
      icon and endowed it with a quasi-ethical authority. My commentary is not an item
      by-item apologia for the Council's report. I do agree with, and wish to defend,
      its emphasis on the primacy of the physician's obligation to his or her patient
      even in a managed-care system. But I also agree with Miles and Koepp that a
      fuller development of an ethic of distributive justice is in order. I suspect
      they would frame their ethic differently than would I. I do not agree with them,
      however, that disclosure of interests would help to judge the ethical validity of
      the Council's opinions, except in a limited way. Lest I be suspected of a
      conflict of interest, I must state at the outset that I had no part in drafting
      the Council's report and that I have no personal or intellectual commitment to
      fee-for-service per se. The report did cite a work of mine, however, and I do
      have an interest in clarifying its relevance to the issues in question.

PMID- 8750590
TI  - A response to "Comments on the AMA report 'ethical issues in managed care'".

PMID- 8750591
TI  - The threat of the new managed practice of medicine to patients' autonomy.

PMID- 8750592
TI  - Managed care and the new medical paternalism.

PMID- 8750593
TI  - Disposable doctors: incentives to abuse physician peer review.
AB  - The following actual cases illustrate a disturbing trend in medicine, one that
      raises ethical issues that are especially important when considering how economic
      incentives and disincentives may affect the practice of medicine.

PMID- 8750594
TI  - Physician advocacy for patients under managed care.

PMID- 8750595
TI  - Medical ethics in the era of managed care: the need for institutional structures
      instead of principles for individual cases.

PMID- 8750596
TI  - The patient as commodity: managed care and the question of ethics.
AB  - Managed care has come to the fore in the medical landscape with such rapidity,
      vigor, and nearly evangelical zeal that startled witnesses to the transformation
      have reacted with awe and outrage. In this article we will take a sober look at
      the system that has in some markets all but consumed the fee-for-service
      relationships that characterized healthcare just five years ago and dominated the
      last failed debate on healthcare reform. We will look at selected arguments for
      and against the justice of such a system, raise pertinent ethical concerns about
      managed care, and suggest some normative guidelines that a society ought to
      develop as a way of regulating the medical commons. In the emerging debate about
      ethical conflicts in the rapidly developing market of managed healthcare, it is
      critical to remember that all care that is given to patients is managed by
      someone. The need for management is a function of how healthcare delivery is
      organized--relying on the intervention of a host of strangers, and, to some
      extent, the cooperation of a large industrialized state. Strangers must agree on
      the parameters of care that will address any given expressed need. Even the
      embodied experience of the patient is named, defined, and categorized not by the
      patient, but by a stranger, who then, by evaluating the patient's pain,
      treatment, and outcome, becomes part of the management and narrative of the case.
      Who owns the instruments, regulates the drugs, and pays the fees will be a
      critical factor in who sets the parameters and limits in healthcare. What makes
      the reality of management a subject of ethical discourse is the issue of power,
      the problem of the marketplace relationships that exist simultaneously, and the
      norms that ought to guide stranger-to-stranger interaction in a just social
      order.

PMID- 8750597
TI  - Conflicts of interest, conflicting interests, and interesting conflicts.

PMID- 8750598
TI  - Inner turmoil: an important consideration in conflicts of interest.

PMID- 8750599
TI  - Surrogates and uncertainty.

PMID- 8750600
TI  - More regarding "Circular Questioning".

PMID- 8750601
TI  - Blood-brain barrier transport of amino acids in healthy controls and in patients
      with phenylketonuria.
AB  - Blood-brain barrier permeability to phenylalanine and leucine in four patients
      with phenylketonuria and in four volunteers was measured five times by the double
      indicator method at increasing plasma concentrations of phenylalanine. Based on
      the permeability-surface area product (PS) from blood to brain (PS1) and on
      plasma phenylalanine levels, Vmax and the apparent Km for phenylalanine were
      determined. Statistically significant relationships between plasma phenylalanine
      and PS1 were established in three out of four volunteers, the average Vmax value
      being 46.7 nmol/g per min and the apparent Km 0.328 mmol/L. Owing to saturation
      of the carrier, such a relationship could not be established in the patients. In
      phenylketonuria, PS1 for phenylalanine and leucine decreased significantly by 55%
      and 46%, respectively. Transport from brain back to blood, PS2, decreased
      significantly and cerebral large neutral amino acid net uptake was generally
      decreased in patients with phenylketonuria. In conclusion, the transport of L
      phenylalanine across the human blood-brain barrier follows Michaelis-Menten
      kinetics. In phenylketonuria, brain permeability to large neutral amino acids is
      reduced by about 50% and net uptake appears decreased.

PMID- 8750602
TI  - Non-ketotic hyperglycinaemia presenting as pachygyria.
AB  - A 2-day-old infant with lethargy and hypoventilation had pachygyria and agenesis
      of the corpus callosum on CT scan. Increased concentrations of glycine in plasma
      and CSF, together with an increased CSF/plasma ratio, confirmed a clinical
      diagnosis of non-ketotic hyperglycinaemia. This is the first report of pachygyria
      in this disorder, although agenesis of the corpus callosum is well recognized,
      and non-specific gyral malformations have been described previously. The specific
      diagnosis of an inborn error of metabolism in infants with structural brain
      malformations is of critical importance for accurate genetic counseling.

PMID- 8750603
TI  - Fish odour syndrome: verification of carrier detection test.
AB  - An oral trimethylamine challenge test has been used to confirm the heterozygous
      status of patients with 'fish-odour syndrome'. By measuring the percentage of
      total urinary trimethylamine-related material excreted as the N-oxide, no
      discrimination could be made between obligate heterozygotes (parents of 'fish
      odour syndrome' patients) (n = 15; 96 +/- 2%, range 92-98%) and control
      individuals (parents of unaffected children) (n = 16; 96 +/- 2%, range 93-99%) on
      a normal diet. However, after ingesting a trimethylamine load (600 mg base) the
      obligate heterozygotes were clearly distinguishable (76 +/- 3%, range 71-79%)
      from controls (95 +/- 2%, range 91-99%) (t-test; p <0.001). One of a hundred
      apparently normal volunteers who were subsequently challenged with trimethylamine
      had a N-oxidation capacity which fell within the range found among the obligate
      heterozygotes.

PMID- 8750604
TI  - Identification of N-acetyl-S-(3-oxo-3-carboxy-n-propyl)cysteine in the urine of a
      patient with cystathioninuria using LC/APCI-MS.
AB  - A new cystathionine metabolite has been identified in the urine of a patient with
      cystathioninuria using liquid chromatography-mass spectrometry with an
      atmospheric pressure chemical ionization interface system (LC/APCI-MS). By this
      method a very intense quasi-molecular ion was observed as a base peak of
      synthetic N-acetyl-S-(3-oxo-3-carboxy-n-propyl)cysteine (NAc-OCPC). The
      quasimolecular ion [M + H]+ of NAc-OCPC observed in the urine of a patient with
      cystathioninuria was the same as that of the authentic compound (m/z 264). The
      retention time and Rf value on paper chromatography of the synthetic compound
      were the same as those of the urinary compound from the patient with
      cystathioninuria. From these results, this new cystathionine metabolite was
      identified as N-acetyl-S-(3-oxo-3-carboxy-n-propyl)cysteine.

PMID- 8750605
TI  - Clinical, biochemical, and molecular analysis of a maternally inherited case of
      Leigh syndrome (MILS) associated with the mtDNA T8993G point mutation.
AB  - We report a new case of Leigh disease (subacute necrotizing encephalomyelopathy)
      in a girl with mitochondrial DNA (mtDNA) mutation in the ATPase6 gene at
      nucleotide position 8993. Sequence analysis of mtDNA revealed a T-to-G
      transversion at nucleotide position 8993 in the ATPase6 gene. Southern blot
      restriction analysis of patient muscle mtDNA showed only a mutant pattern for the
      mutation 8993. Molecular analysis of seven subjects from the family showed that
      except for the father they all carried the 8993 mtDNA mutation in all studied
      tissues, with high percentages in the two symptomatic children and even in one
      asymptomatic boy.

PMID- 8750606
TI  - Biotinidase Km-variants: detection and detailed biochemical investigations.
AB  - We describe a simple method for the detection of biotinidase Km-variants and
      detailed biochemical investigations in 5 such patient. They were detected among
      103 patients with plasma biotinidase activity which ranged from undetectable to
      30% of the mean normal value. Two different types of biotinidase Km-variants were
      found. (1) In 3 infants biotinidase had a single 105-430-fold elevated Km for
      biocytin. Biotinidase showed very low activities (0.2-4% of the mean normal
      value) in the routine colorimetric assay and was not functional in vivo.
      Accordingly, these patients presented with classical clinical illness. (2) In two
      patients biotinidase showed biphasic kinetics indicating the presence of one
      component with a normal Km and reduced Vmax (1.7% and 12%), and another with 330-
      and 59-fold elevated Km, respectively. In these two patients, biotinidase proved
      to be at least partially functional in vivo. However, the first patient developed
      severe symptoms and biotin deficiency late, at the age of 10-15 years, and the
      second had marginal biotin deficiency at the age of 2 years but no clinical
      symptoms. Comparative studies revealed that both patients had more severe biotin
      deficiency than age-matched patients with similar levels of residual biotinidase
      activity and a single normal Km. Therefore, all patients with residual
      biotinidase activity should be evaluated for the presence of a Km-mutation, since
      such patients should be treated with biotin. These can easily be detected by
      including a second substrate concentration (1.5 mmol/L) in the routine
      colorimetric biotinidase assay which is performed with 0.15 mmol/L biotin.
      Increased activity with the higher substrate concentration indicates the presence
      of a Km-mutation. Detailed kinetic studies are needed to evaluate the distinct
      forms of Km-variants.

PMID- 8750607
TI  - Reversible metabolic myopathy in biotinidase deficiency: its possible role in
      causing hypotonia.
AB  - A 5-year-old girl diagnosed with biotinidase deficiency at 9 months of age
      demonstrated limb and axial hypotonia which improved on biotin therapy. In this
      patient, electromyographic (EMG) studies prior to treatment were compatible with
      a mild myopathic process. Serial EMGs performed on biotin therapy demonstrated a
      gradual resolution of the myopathy. This is the first documented case of a
      reversible myopathy in a patient with biotinidase deficiency, which may
      contribute to the clinical findings of hypotonia.

PMID- 8750608
TI  - Assignment of the human peroxisomal palmitoyl-CoA oxidase gene to chromosome
      17q23-qter by PCR technique.
AB  - Human peroxisomal palmitoyl-CoA oxidase plays a pivotal role in the beta
      oxidation of fatty acids. Its importance is reflected by the severity of the
      disease associated with its deficiency in man. The gene was previously mapped to
      chromosome 17q25 with a FISH technique and is now confirmed using a PCR
      technique.

PMID- 8750609
TI  - Pseudodeficiency of arylsulphatase A: strategy for clarification of genotype in
      families of subjects with low ASA activity and neurological symptoms.
AB  - A benign deficiency (pseudodeficiency) of the lysosomal enzyme arylsulphatase A
      (ASA) (EC 3.1.6.8) towards synthetic substrates complicates the diagnosis of
      metachromatic leukodystrophy (MLD). The pseudodeficiency is due to a single base
      substitution in the 3'-untranslated region of the ASA gene (1524+95 A-->G) and it
      has been reported that this mutation (PD2) always occurs on a chromosome carrying
      a second mutation in the ASA gene (PD1), which abolishes an N-glycosylation site
      (N350S). Analysis of the two PD mutations in the ASA gene separately was carried
      out in a large group of subjects with neurological symptoms and low ASA activity,
      including close relatives and MLD patients. The relationship between ASA enzyme
      activity and the different genotypes identified is presented. Evidence for the
      existence of an allele containing the PD2 mutation alone is presented. A strategy
      for cases with low ASA activity and neurological symptoms in families carrying a
      PD allele or both PD and MLD alleles is proposed.

PMID- 8750610
TI  - Elevated plasma chitotriosidase activity in various lysosomal storage disorders.
AB  - Recently a striking elevation of the activity of chitotriosidase, an endo beta
      glucosaminidase distinct from lysozyme, was found in plasma from patients with
      Gaucher type I disease (McKusick 230800). Plasma chitotriosidase originates from
      activated macrophages and this elevation is secondary to the basic defect in
      Gaucher disease. To investigate the specificity of this phenomenon, we have
      investigated 24 different lysosomal storage diseases. In 11 different diseases
      increased chitotriosidase activity in plasma was found (in 28% of the patients).
      None of these diseases showed elevations as high as in Gaucher disease.
      Chitotriosidase was not significantly elevated in plasma from 20 different non
      lysosomal enzymopathies or in plasma from patients with infectious diseases
      associated with hepatomegaly. The results show that marked elevation of
      chitotriosidase activity in plasma appears to be specific for Gaucher disease.
      The data further suggest that elevated levels of chitotriosidase activity in
      plasma from patients with unexplained diseases may be indicative for a lysosomal
      disorder.

PMID- 8750611
TI  - Genotyping of a patient homozygous for a rare apolipoprotein E1 [Gly127-->Asp;
      Arg158-->Cys] (Weisgraber allele).
AB  - We examined the apolipoprotein E polymorphism of an obese patient presenting non
      insulin-dependent diabetes, hypertension and moderate lipid disturbances. The
      apolipoprotein E genotyping carried out from leukocyte DNA using PCR
      amplification and restriction enzyme digestion demonstrated homozygosity for the
      rare apoE1[Gly127-->Asp; Arg158--> Cys] (Weisgraber allele). The nucleotide
      change results in a glycine to aspartic acid substitution at amino acid 127 in
      the apolipoprotein E2.

PMID- 8750612
TI  - Fatty acid content in lymphocytes from children with syndromic paucity of
      interlobular bile ducts, Alagille syndrome.
AB  - Fatty acid (FA) concentrations were studied in lymphocytes isolated from children
      with syndromic paucity of interlobular bile ducts (PILBD), Alagille syndrome. The
      aim of this study was to assess whether the specific FA changes previously
      observed in fibroblast cultures from such patients were also present in other
      tissues. Lymphocyte FA, obtained both from controls and patients were studied
      under two experimental conditions, either after separation of the mononuclear
      cells or after 48 hours of culture. Freshly isolated lymphocytes from patients
      presented few FA changes compared to the controls. However, when patient
      lymphocytes were placed in culture medium for 48 hours, FA changes were amplified
      compared to those observed in controls; the decrease in the sum of saturated and
      n-6 polyunsaturated FA of total lipids was significant only in patients, and the
      n-3 FA of phospholipids was strikingly increased in patients (p < or = 0.001),
      compared to controls. These results are related to those previously observed in
      fibroblast cultures and suggest that placing cells in culture could reveal a pre
      existing cellular abnormality in patients with PILBD.

PMID- 8750613
TI  - Lesch-Nyhan syndrome and its pathogenesis: normal nicotinamide-adenine
      dinucleotide but reduced ATP concentrations that correlate with reduced poly(ADP
      ribose) synthetase activity in HPRT-deficient lymphoblasts.
AB  - In hypoxanthine (guanine) phosphoribosyltransferase- (HPRT; EC 2.4.2.8) deficient
      lymphoblasts, ATP but not nicotinamide-adenine dinucleotide coenzyme
      concentrations are reduced by limited nutrition. Such reduced ATP concentrations
      are correlated with reduced poly(ADP-ribose) synthetase (polyADPRT; EC 2.4.2.30)
      activity; this reduces the breakdown of nicotinamide-adenine dinucleotide
      coenzymes and thus explains their normal intracellular concentrations. Since
      reductions in poly(ADP-ribose) synthetase activity reduce DNA repair, alterations
      in DNA could accumulate even in non-multiplying cells such as neurons, especially
      in the continuously active 'respiratory centre'. Our Lesch-Nyhan patients
      suffered respiratory deaths between 15 and 20 years of age.

PMID- 8750614
TI  - Metabolic coma with ketoacidosis and hyperglycaemia in 2-methylacetoacetyl-CoA
      thiolase deficiency.

PMID- 8750615
TI  - Biotinidase activity in patients with phenylketonuria.

PMID- 8750616
TI  - Plasma creatine kinase and cardiomyopathy in glycogen storage disease type III.

PMID- 8750617
TI  - Phenylketonuria mutations in southern Chinese detected by denaturing gradient gel
      electrophoresis in exon 7 of PAH gene.

PMID- 8750618
TI  - Interleukins and colony stimulating factors in human myeloid leukemia cell lines.
AB  - The present review has summarized the expression, production and effects of the
      human interleukins (IL) 1-11 and myelopoietic colony stimulating factors (CSF) in
      the established myeloid leukemia cell lines and in cells from patients with acute
      myeloid leukemia as well as the oncogene expression reported in these myeloid
      leukemia cell lines. The genetic dissection of leukemic myelopoiesis may provide
      new perspectives for the control of myeloid leukemias. Based on their expression
      of phenotypic markers (e.g., surface antigens, cytochemical staining, etc.),
      myeloid cell lines can be further subdivided into myelogenous, monocytic,
      erythroid and megakaryoblastic leukemia cell lines. Due to the close relationship
      of erythroid and megakaryoblastic progenitor cells and to the existence of a
      probably common precursor cell giving rise to these two different cell lineages,
      many megakaryoblastic cell lines express erythroid markers (e.g., expression of
      hemoglobin or glycophorin A) and conversely cell lines with a predominant
      erythroid profile might display megakaryoblastic features (e.g., platelets
      peroxidase or glycoproteins CD41, CD42b or CD61). The recent cloning of the
      specific cytokine: thrombopoietin (TPO) and its receptor generated a strong
      interest in these particular myeloid cell lines that are discussed in more detail
      in the present review. Both normal and leukemic megakaryocytopoiesis are
      stimulated by granulocyte-macrophage colony stimulating factor (GM-CSF), IL-3, GM
      CSF/IL-3 fusion protein, IL-6, IL-11 and TPO but inhibited by IL-4, interferon
      alpha (IFN-alpha) and IFN-gamma. Human megakaryoblastic leukemia cell lines have
      common biological features: high expression of the megakaryocytic specific
      antigen (CD41); high expression of early myeloid antigens (CD34, CD33 and CD13);
      constitutive expression of IL-6 and platelet-derived growth factor; a complex
      karyotype picture; expression of c-kit (the stem cell factor receptor); growth
      dependency or -stimulation by IL-3 and/or GM-CSF; and in vivo tumorigenicity in
      mice associated with marked fibrosis. Whereas numerous chemical and biologic
      agents induce granulocytic and/or monocytic differentiation of myeloid leukemia
      cell lines, only a few agents including phorbol myristate acetate, vitamin D3,
      IFN-alpha, IL-6 and thrombin have been reported to induce megakaryocytic
      differentiation in the megakaryoblastic leukemia cells.

PMID- 8750619
TI  - Myelopoiesis in myelodysplasia evaluated by multiparameter flow cytometry.
AB  - Evaluating the proliferative activity of the immature erythro- and myelopoiesis
      as well as the mature myelopoiesis in 21 MDS patients and 14 healthy controls by
      simultaneously staining bone marrow cells for surface phenotype and DNA content,
      we found the percentages of proliferating S-phase cells in the early stage of MDS
      were higher. With disease progression evaluated by the FAB classification this
      parameter decreased significantly for both the immature myelo- and
      erythropoiesis. Evaluation of the proliferative activity of the mature
      myelopoiesis defined by the CD66 antigen revealed no difference between the
      normal controls and the MDS patients. Using another assay simultaneously
      labelling bone marrow cells for three leucocyte differentiation antigens during
      treatment with GM-CSF and low-dose AraC the cells clearly differentiated in one
      case. In another patient the disease seemed to progress as evaluated by cells
      only expressing immature antigens. The above mentioned immunophenotypic changes
      persisted at least one month after termination of treatment. In conclusion, the
      evaluation of proliferation and differentiation of leucocyte subsets using
      multiparameter flowcytometric assays in myelodysplastic patients from different
      FAB groups before as well as during treatment with haemopoietic growth factors
      may prove valuable in the future.

PMID- 8750620
TI  - Angiogenesis in B cell lymphoproliferative diseases. Biological and clinical
      studies.
AB  - Angiogenesis is a necessary step in solid tumor progression (growth, invasion and
      metastasis) with which it correlates and is indicative of an unfavourable
      prognosis. We observed bone marrow angiogenesis in patients with active multiple
      myeloma (MM), though not in patients with non-active MM nor with monoclonal
      gammopathies of undetermined significance (MGUS). Microvessel density increased
      in parallel with the labeling index (LI%)--an indicator of plasma cell
      proliferating activity that correlates with prognosis--and defined a risk of MM
      progression in much the same way as LI% itself. Consequently, bone marrow
      angiogenesis could be an indication for unfavourable prognosis in MGUS and MM.
      Angiogenesis has also been demonstrated in lymph nodes involved by B cell non
      Hodgkin's lymphoma (B-NHL) belonging to the Working Formulation intermediate
      grade (diffuse subtypes), and high-grade categories, but not in the low-grade and
      intermediate-grade (follicular subtype) categories. It correlated with the B-NHL
      cell proliferating activity, since large increments in this activity have already
      been demonstrated in intermediate- and high-grade vs low-grade tumors. Active MM,
      intermediate-grade, diffuse subtypes, and high-grade B-NHLs correspond to the
      vascular phases of B cell lymphoproliferative diseases, and could thus be
      assimilated to locally invasive and metastatic solid tumors. Similarly to solid
      tumors during these stages of progression, tumor B cells are also capable of
      inducing angiogenesis, both directly and indirectly by activating the
      inflammation infiltrate--a possibility that was first demonstrated by means of B
      NHL implants onto the chick embryo chorioallantoic membrane. Anti-angiogenic
      therapy can be envisaged as a possible future development.

PMID- 8750621
TI  - TGF-beta and megakaryocytes in the pathogenesis of myelofibrosis in
      myeloproliferative disorders.
AB  - Myeloproliferative disorders are clonal disorders of the hematopoietic stem cell
      and comprise a spectrum of more or less well-defined clinical entities:
      polycythaemia vera, chronic myeloid leukemia, essential thrombocythaemia, and
      agnogenic myeloid metaplasia. Myelofibrosis, which contributes substantially to
      the impaired hematopoiesis, is commonly observed in myeloproliferative disorders
      but it represents the criterion of agnogenic myeloid metaplasia also termed
      idiopathic myelofibrosis. Although progress has been made in the elucidation of
      the pathogenesis of myelofibrosis, it still remains unclear. The aim of this
      review is to address the new insights that outline the potential role of TGF-beta
      in the promotion of myelofibrosis, through its release from
      megakaryocytes/platelets, particularly in agnogenic myeloid metaplasia.

PMID- 8750622
TI  - TCR delta gene rearrangements in acute myeloid leukemia with T-lymphoid antigen
      expression.
AB  - In this review we present our data concerning T-cell receptor (TCR) delta gene
      rearrangements in acute myeloid leukemia with coexpression of T-lymphoid features
      (CD2/CD4/CD7; Ly+ AML). We found a correlation between TCR delta gene
      rearrangements and coexpression of these T-lymphoid features. Ten of 66 Ly+ AML
      and only one of 44 AML cases without this coexpression exhibited TCR delta gene
      rearrangements (p = .028). In contrast, no correlation was observed between
      terminal deoxynucleotidyl transferase (TdT) expression and the occurrence of TCR
      delta gene rearrangements in AML. Rearrangements were found in two of 25 AML with
      and seven of 71 AML cases without TdT expression. Interestingly, nucleotide
      sequencing of junctional sites revealed up to 36 N-nucleotides in cases without
      or with only weak TdT expression indicating downregulation of TdT expression
      after the TCR rearrangement took place. Complete V delta 1J delta 1 and
      incomplete D delta 2J delta 1 gene rearrangements were observed most frequently
      in Ly+ AML. These recombination patterns were similar to patterns observed in
      acute T-lymphoblastic leukemia with coexpression of myeloid features (My+ T-ALL)
      suggesting transformation of a common myeloid/T-lymphoid progenitor cell in these
      cases.

PMID- 8750623
TI  - Human umbilical cord blood for hematopoietic progenitor cells transplantation.
AB  - Human umbilical cord blood (HUCB) represents a unique source of transplantable
      hematopoietic progenitor cells. HUCB from a newborn sibling has been used
      successfully for hematopoietic reconstitution of more than 50 children with
      congenital and malignant diseases. Moreover, 13 HUCB transplants have been
      performed from unrelated donors. Bone marrow transplantation (BMT) has rapidly
      progressed over the last two decades offering cure and prolonged disease free
      survival in patients with hemato-oncological malignancies, metabolic and genetic
      disorders. BMT is limited by the paucity of HLA-matched donors and the morbidity
      and mortality due to graft-versus-host disease (GVHD). HUCB could alleviate some
      of the problems associated with BMT and establishment of HUCB bank and registries
      could become an easily available source of suitable stem cells for
      transplantation. This review focuses on identifying current scientific problems
      and clinical achievement as well as noting the most recent developments in the
      field with special attention to the collection, processing, cryopreservation, and
      banking of HUCB. Progenitor cells from cord blood may provide an excellent
      vehicle for future gene therapy. As a result of relative immunodeficiency at
      birth, it is likely that partially matched unrelated cord blood transplants (CBT)
      would be successful due to a lower risk of GVHD related problems. Therefore, the
      establishment of large cord blood banks is of the utmost importance, in the
      future.

PMID- 8750624
TI  - Clinical course and outcome of patients with Hodgkin's disease who progress after
      autologous transplantation.
AB  - Twenty-six of fifty-eight patients undergoing autologous bone marrow
      transplantation (autoBMT) or peripheral stem cell transplantation (PSCT) for
      Hodgkin's disease had progression of lymphoma (Hodgkin's or non-Hodgkin's) during
      the course of their follow-up. The majority of progressions, 81% (21/26),
      occurred within the first year of transplant; 12% (3/26) occurred at three years
      or more. Three patients developed a non-Hodgkin's lymphoma; all B-cell tumors
      primarily involving the gastrointestinal tract. The majority of patients (23/26)
      received at least one therapy after progression and 65% (17/26) of patients
      received multiple therapies. One patient who received a second BMT is alive
      without evidence of disease at 49 months following the second autologous BMT. The
      median survival for the entire group is 11 months. Forty-six percent (12/26) of
      patients survived more than one year and twenty-three percent (6/26) survived
      more than two years after disease progression. Post-progression survival is
      significantly related to time to progression.

PMID- 8750625
TI  - Effects of BCR-ABL antisense oligonucleotides (AS-ODN) on human chronic myeloid
      leukemic cells: AS-ODN as effective purging agents.
AB  - We examined phosphorothioate oligodeoxyribonucleotides (ODNs) directed against
      bcr in exon 3 or exon 2, which are rearranged with exon 2 of abl (B3A2 and B2A2)
      at t(9;22) of chronic myelogenous leukemia (CML). Since these ODNs are designed
      to be CML cell specific, we studied their effects on the human CML cell line
      K562, which is known to have B3A2 rearrangement, and leukemic cells from
      patients, as well as normal hematopoietic stem cells in vitro. In vitro
      experiments were performed to determine a potential role of these two ODNs as ex
      vivo purging agents. Incubation of B3A2 antisense at 40, 80, and 120
      micrograms/ml with K562 CML cells for 72 hours at 37 degrees C resulted in 44%,
      56%, and 63% reduction of CFU-L as compared to controls. In contrast, B3A2 sense
      and B2A2 antisense had no significant growth inhibitory effect on K562 cells.
      Incubation of B3A2 and B2A2 antisense ODNs at concentration of 80 micrograms/ml
      at 37 degrees C for 36 hours with normal peripheral blood stem/progenitor cells
      (PBSC) resulted in 124% and 98% CFU-GM formation as compared to untreated
      controls, respectively. However, incubation of PBSC with B3A2 and B2A2 sense-ODNs
      resulted in a 22% and 44% reduction in CFU-GM, respectively. In order to
      determine the ex vivo purging effects of bcr-abl ODNs, the K562 cells were mixed
      with PBSC from normal donors at a ratio of 1:20 (CML:PBSC). The mixture of cells
      was then incubated with B3A2 antisense at 80 micrograms/ml for 36 hrs at 37
      degrees C. After incubation, no CML cells were detected by fluorescence in situ
      hybridization (FISH) as compared to untreated controls. These results were
      confirmed by RT-PCR using bcr-abl primers and mRNA isolated from the mixture of
      cells. Further, these results support the hypothesis that bcr-abl antisense ODNs
      are potentially effective agents for ex vivo purging of autologous stem cells
      before transplantation to eliminate/reduce the burden of leukemic cells. No
      significant toxicity to normal hematopoietic stem/progenitor cell population by
      the bcr-abl antisense ODNs was observed. Although unanticipated reductions in
      normal hematopoietic progenitor cells (CFU-GM) were observed with sense ODNs, no
      reduction in CFU-GM was observed with unrelated phosphorothioate ODN controls.

PMID- 8750626
TI  - Interleukin-1 and tumor necrosis factor alpha induce class 1 aldehyde
      dehydrogenase mRNA and protein in bone marrow cells.
AB  - Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) protect normal
      human hematopoietic progenitors from the toxicity of 4
      hydroperoxycyclophosphamide (4-HC). Aldehyde dehydrogenase Class 1 (ALDH-1) is
      the enzyme that inactivates 4-HC. Diethylaminobenzaldehyde (DEAB), a competitive
      inhibitor of ALDH-1, was shown to prevent the protective effects of IL-1 and TNF
      alpha. In this study, we examined the effect of IL-1 and TNF alpha on the
      expression of ALDH-1 in normal bone marrow as well as malignant cells. ALDH-1
      mRNA and protein were quantified using Northern and Western blotting,
      respectively. In addition, the ALDH-1 enzyme activity in untreated as well as IL
      1 and TNF alpha treated bone marrow cells was determined spectrophotometrically.
      The role of glutathione (GSH) in the protection against 4-HC toxicity was also
      studied. The results show that pretreatment with IL-1 and TNF alpha for 6 h or 20
      h increase the expression of ALDH-1 mRNA and protein, respectively, in human bone
      marrow cells. In contrast, IL-1 and TNF alpha treatment did not affect the ALDH-1
      expression in several leukemic and solid tumor cell lines, regardless of whether
      or not ALDH-1 is expressed constitutively. Furthermore, the ALDH-1 enzyme
      activity was significantly induced in bone marrow cells after 20 h pre-treatment
      with IL-1 and TNF alpha. Finally, the depletion of or inactivation of GSH did not
      affect the protection against 4-HC toxicity. In conclusion, inhibition of the
      protection from 4-HC toxicity by DEAB, together with the increase in ALDH-1
      expression and activity, provide strong evidence that IL-1 and TNF alpha mediate
      their protective action, at least partially, through ALDH-1.

PMID- 8750627
TI  - BCL6 gene rearrangement and other cytogenetic abnormalities in diffuse large cell
      lymphoma.
AB  - Evidence for rearrangement of the BCL6 gene at 3q27 has been documented in 20-30%
      diffuse lymphomas with a large cell component (DLLC), and was found to be of
      prognostic significance at the time of diagnosis. To incorporate these
      observations into current cytogenetic and clinical prognostic models, 76 cases of
      DLLC with known BCL6 status were analyzed. Cytogenetic indicators of progression,
      including trisomy 7, trisomy 12, del(6)(q21q25), and structural alterations of
      17p were less frequent in BCL6 rearranged DLLC compared to BCL6 germline tumors.
      Despite a 93% overall survival at median follow-up of 30 months, a trend for
      continued relapse resulted in a projected freedom from progression for the BCL6
      rearranged cohort of 66% at 4 years, compared to 39% for the BCL6 germline
      cohort. Six cases among the BCL6 rearranged group lacked additional cytogenetic
      indicators of progression and remained free of disease at follow-up in excess of
      7 years, whereas BCL6 rearranged cases with increasing numbers of cytogenetic
      aberrations showed decreased intervals free from progression of disease. These
      results suggest that BCL6 rearrangement should be combined with other known
      clinical and cytogenetic indicators in prognostic analyses of patients with DLLC.

PMID- 8750628
TI  - Clinical evaluation of 451 patients with HIV related non-Hodgkin's lymphoma:
      experience on the Italian cooperative group on AIDS and tumors (GICAT).
AB  - We report the clinical experience in 451 patients with HIV related non-Hodgkin's
      lymphoma (HIV-NHL) observed within the Italian Cooperative Group on AIDS and
      Tumors (GICAT: Gruppo Italiano Cooperativo AIDS e Tumori), a significant number
      of them being treated at the Aviano Cancer Center (ACC). High grade histology
      according to the Working Formulation, stages III-IV and B symptoms were detected
      in the majority of patients. The median survival was 6 months. Based on the Cox
      model, three factors appeared to influence survival: advanced stage, treatment
      received and failure to obtain complete remission (CR). In another study aimed at
      comparing between chemotherapy with or without G-CSF it was shown that G-CSF
      significantly reduced white blood cells (WBC) nadir duration, the mean delays
      between cycles, the mean hospitalization time for toxicity per patient treated,
      without increasing significantly the overall costs. Furthermore, of 77 GICAT
      patients treated at the ACC with (group A) or without (group B) long-lasting CR,
      performance status and the mean CD4+ cell count at time of NHL diagnosis were the
      only parameters of statistical relevance. Based on our data HIV related NHLs are
      highly aggressive malignancies which are associated with a poor prognosis per se,
      and because of the underlying HIV infection. Long-term survivals and possible
      cures can, nonetheless, be obtained in a subgroup of patients, who have a better
      performance status and a less advanced immune dysfunction related to HIV
      infection.

PMID- 8750629
TI  - 16-year experience at M. D. Anderson Cancer Center with primary Ki-1 (CD30)
      antigen expression and anaplastic morphology in adult patients with diffuse large
      cell lymphoma.
AB  - One hundred and seven adult cases of untreated diffuse large cell lymphoma (DLCL)
      were retrospectively analyzed for primary CD30 antigen expression, anaplastic
      morphology, and long-term prognosis. Tissue samples from 36 patients stained
      strongly for CD30, and of these, 22 showed anaplastic morphology. Patients with
      CD30-positive DLCL presented more frequently with skin involvement,
      constitutional symptoms, more advanced Ann Arbor stage disease, and at a younger
      age when compared to patients with CD30-negative DLCL. Both groups had a similar
      complete response rate (78%). Patients with CD30-positive DLCL had a favorable
      survival rate when compared to patients with CD30-negative DLCL, although the
      difference was not statistically significant (73% vs. 55%, p = 0.28). Among the
      CD30-positive DLCL patients, those with anaplastic morphology presented more
      frequently with extranodal disease and T-cell phenotype when compared to patients
      with non-anaplastic morphology, but both groups had similar rates of complete
      response and long-term survival. All 107 patients were treated initially with a
      doxorubicin-containing chemotherapy regimen. These findings suggest a favorable
      outlook for adult patients with DLCL that has primary CD30 antigen expression
      regardless of the presence or absence of anaplastic morphology. Which support our
      previous observations.

PMID- 8750630
TI  - Efficacy of delayed granulocyte colony-stimulating factor after full dose CHOP
      therapy in non-Hodgkin's lymphoma: a pilot study for a leukocyte count oriented
      regimen.
AB  - Bone marrow toxicity is a great challenge for physicians treating patients with
      non-Hodgkin's lymphoma (NHL) and prescribed chemotherapy. Granulocyte colony
      stimulating factor (G-CSF) prevents myelotoxicity, but the optimal timing and
      scheduling of G-CSF administration has not been ascertained. We investigated
      leukocyte count oriented G-CSF administration schedules, as related to full dose
      administration of cyclophosphamide, adriamycin, vincristine, and prednisolone
      (CHOP) chemotherapy, with shortened intervals. Thirty-eight Japanese patients
      with NHL were included in this study. The standard CHOP combination was
      administered in six cycles. Patients were given G-CSF in a dose of 2
      micrograms/kg/day, subcutaneously starting the day when total leukocytes were <
      3,000/microliters. When leukocyte count remained at > 3,000/microliters, G-CSF
      was started 10 days following CHOP. Treatment with G-CSF was discontinued after
      the leucocyte count reached > 10,000/microliters, and CHOP was started the next
      day (CHOP-G treatment; CHOP-G). Doses were not modified in any patient. Patients
      over 70 years of age received 2/3 of the standard dosage. In the first cycle of
      CHOP, the day of initiation of G-CSF was 9.6 days following CHOP in the first
      cycle and 7.7 to 8.5 days during 2 to 6 cycles. The mean duration of G-CSF
      injection was 7.4 days with a range from 6.8 to 8.0 days, in each CHOP cycle. The
      mean intervals of CHOP-G was 14.7 days during six consecutive courses, and there
      was no prolongation of the intervals, even in later cycles. In 23 patients who
      received all six cycles of CHOP-G, the overall response rate was 91.3% (73.9%
      complete remission; CR and 17.4% partial remission; PR). In 32 patients with
      intermediate grade NHL, the overall response rate was 84.4% (65.5% CR and 18.8%
      PR). Thus, the full dose CHOP with G-CSF, based on the leukocyte count oriented
      schedule, can be achieved with shortened intervals, an approach which will
      increase the quality of life (QOL) for the patients by reducing the days of
      treatment as well as the cost of G-CSF.

PMID- 8750631
TI  - Analysis of 14q+ derivative chromosomes in non-Hodgkin's lymphomas by
      fluorescence in-situ hybridization.
AB  - The most common chromosomal abnormality observed in non-Hodgkin's lymphomas (NHL)
      involves the structural alteration of the q arm of chromosome 14. It is not
      always possible, however, to fully analyse such derivative chromosomes by Giemsa
      banding. Therefore, we have applied the fluorescence in-situ hybridization (FISH)
      technique of chromosome painting to elucidate the origins of the der(14)
      chromosomes in 8 cases of NHL. In 2 NHL the der(14) appeared to be the product of
      the t(14;18)(q32;q21) translocation, but were not accompanied by the reciprocal
      der(18) chromosome. In 3 cases the breakpoint was at 14q32 but the translocated
      material appeared not to be from chromosome 18 and in 2 cases the breakpoint was
      centromeric to 14q32. One case with a t(14;18)(q32;q21) was also analysed as a
      control. Dual painting was carried out with paints for chromosome 14 and either
      chromosome 3, 8, 10, 11, 18 or 19. In the control and 2 other cases the
      translocated material was demonstrated to be from chromosome 18, in two cases it
      was from chromosome 3 and in 1 case there was an unusual insertion of chromosome
      11 material. We were unable to identify the origins of the translocated material
      in 1 NHL and in the final case the apparent der(14) was demonstrated not to
      contain chromosome 14 material. These data demonstrated the utility of the FISH
      technique for analysing malignant cell karyotypes, and in particular indicated
      the potential of this approach for identifying cases containing putative NHL
      associated oncogenes that may have been translocated adjacent to the
      immunoglobulin locus at 14q32.

PMID- 8750632
TI  - Bone marrow findings further support the hypothesis that essential mixed
      cryoglobulinemia type II is characterized by a monoclonal B-cell proliferation.
AB  - One-hundred-sixteen consecutive bone-marrow biopsies were taken from 76 patients
      with essential mixed cryoglobulinemia type II (type II cryo), whose median follow
      up was 97 months. Fifty-four out of fifty-six subjects who underwent ELISA and
      RIBA tests for HCV, were found to be positive. At conventional light microscopic
      examination, 64/76 patients showed discrete lymphoid infiltrates consisting of
      small elements with plasmacytoid differentiation and with frequent paratrabecular
      location. Thirty-nine biopsies were studied by immunohistochemistry that revealed
      the B-cell nature of the infiltrates (CD20+, CD45RA+, CD79 alpha+, CD3-, CD45RO
      ), with demonstrable monotypic Ig light-chain restriction in 22 cases. It is
      worthy of note that the lymphoid elements usually appeared protected against
      apoptosis, because of the strong expression of the bcl-2 oncogene product, and
      provided with a very low proliferative capacity, the Ki-67 index being lower that
      3%. The latter findings are in keeping with the indolent behaviour of the clonal
      lymphoid population observed in type II cryo and allow some speculation as to the
      need for environmental stimuli for its maintenance as well as further mutagenic
      events for its eventual transformation into an overt lymphoma.

PMID- 8750633
TI  - Phenotype of Hodgkin and Sternberg-Reed cells and expression of CD57 (LEU7)
      antigen.
AB  - Possible associations between the immunophenotype of Hodgkin (H) and Sternberg
      Reed (S-R) cells, the expression of CD57 (Leu 7) antigen, and the presence of
      Epstein-Barr virus (EBV) were investigated in lymph node specimens from 50 cases
      of Hodgkin's disease (HD), including 26 cases of mixed cellularity and 24 cases
      of nodular sclerosis. Tissues were fixed in 10% neutral formalin, or/and B5
      solution. H and S-R cells were CD30+, CD15+ (85% of the cases) and LCA (CD45). A
      proportion of neoplastic cells positive for either T-cell markers (CD3) or B-cell
      markers (CD20) was observed in 10% and 34% of the cases, respectively. Membrane
      positivity for CD57 antigen was found in H and S-R cells in 10 cases (8 cases of
      mixed cellularity, and 2 cases of nodular sclerosis). Such immunopositivity was
      only observed in B5-fixed sections. No staining for CD57 antigen was identified
      in H and S-R cells of any case with CD20 positive neoplastic cells. H and S-R
      cells of both CD57-positive and CD57-negative cases were further studied by
      immunohistochemistry for LMP1, by in-situ hybridization for EBER and by
      polymerase chain reaction (PCR) for EBV-DNA. No association was identified
      between the expression of CD57 antigen and the presence of EBV sequences,
      transcripts or proteins. Our findings do not support a B-cell origin for H and S
      R cells in CD57-positive cases of Hodgkin's disease and suggest that these
      neoplastic cells may be related to natural killer (NK) or T-cells expressing CD57
      antigen.

PMID- 8750634
TI  - Cyclosporine A in chronic lymphocytic leukemia: dual anti-leukemic and
      immunosuppressive role?
AB  - The association of hemolytic anemia and other autoimmune cytopenias with chronic
      lymphocytic leukemia (CLL) is well known. The etiology of these immune syndromes
      is still uncertain, despite evidence that the putative cell of origin of the B
      CLL cell produces naturally occurring autoantibodies. Cyclosporine A is effective
      in treating the immune manifestations associated with CLL and, occasionally, has
      shown anti-leukemic activity. We report two cases in which cyclosporine A
      treatment of autoimmune hemolytic anemia resulted in reduction of CLL cell
      burden. We then discuss the possible mechanism of action of cyclosporine A and
      the nature of the autoimmune processes involved.

PMID- 8750635
TI  - Expression and long-term prognostic value of CD34 in childhood and adult acute
      lymphoblastic leukemia.
AB  - Clinical and laboratory characteristics at diagnosis, and long-term (up to 7
      years) evolution, were analysed in 156 patients (66 adults and 90 children) with
      acute lymphoblastic leukemia (ALL), according to the expression of CD34. Eighty
      three patients had CD34+ and 73 patients CD34- blasts at diagnosis. In adults,
      CD34+ ALL was more often of B-lineage (p = .003). White blood cell counts were
      higher both in children with CD34-B-lineage ALL (p = .02) and adults with CD34-T
      lineage ALL (p - .05). Adult patients with CD34-T-lineage ALL were older (p =
      .04) and had more frequent splenic or liver enlargement (p = .02). Children with
      CD34+ ALL had a significantly (p = .04) longer event-free follow-up than CD34-
      children. Survival curves showed that after induction of remission, relapses were
      less frequent during the first 2 years for patients with CD34+ B-lineage ALL.
      After 2 years, however, event-free survival curves of CD34+ and CD34- patients
      merged. Thus it seems that CD34+ has no significant benefit for ALL patients.

PMID- 8750637
TI  - Isolated leukemia cutis and CNS involvement in combination with cytogenetic
      findings of trisomy 8--two case reports.
AB  - We describe two patients who showed a very similar, but atypical course of acute
      myelogenous leukemia. They demonstrated skin nodules, spinal fluid and CNS
      involvement whereas bone marrow and blood remained clear. Nonetheless both had
      cytogenetic findings of trisomy 8 in the marrow and were resistant to a
      combination of cytarabine, idarubicin, fludarabine, and granulocyte-colony
      stimulating factor.

PMID- 8750636
TI  - Is P-glycoprotein a sufficient marker for multidrug resistance in vivo?
      Immunohistochemical staining for P-glycoprotein in children and adult leukemia:
      correlation with clinical outcome.
AB  - Seventy-eight patients: 45 children, 33 adults and 27 normal healthy donors were
      enrolled in the study. Expression of P-glycoprotein (P-gp) was evaluated with
      three monoclonal antibodies (MAb's) directed to intra-(C219, JSB-1) and extra
      cellular (MRK-16) epitopes of P-gp and immunocytochemical (IC) APAAP staining
      method. Twenty-seven healthy donors peripheral blood mononuclear cells (PBMC)
      were investigated by means of IC and FACScan analysis. Positive staining for P-gp
      was detected in 31% children's and 33% adults' leukemia samples. No reactivity of
      three MAb's was observed with peripheral blood mononuclear cells (PBMC) by means
      of IC. Flow cytometry analysis with C219 MAb revealed staining for P-gp present
      on sub-population of lymphocytes and monocytes. P-gp (+) as well as P-gp (-)
      cases were compared in respect to clinical outcome, FAB classification and blood
      group. Complete remission (CR) was achieved in 12/14 (85%) children's and 9/11
      (81%) adults' P-gp (+) leukemia cases. Within the P-gp (-) leukemia cases CR was
      observed in 24/29 (82%) and 18/22 (81%), respectively. Partial remission,
      relapse, resistance and death were noticed in 14% children's and 18% adults' P-gp
      (+) samples. In P-gp (-) cases these parameters were observed in 17% and 18%,
      respectively. These results raise the question whether the expression of P-gp can
      be used as single prognostic marker to detect multidrug resistance (MDR
      phenomenon) in vivo?

PMID- 8750638
TI  - Molecular heterogeneity in childhood precursor B acute lymphoblastic leukemia
      with immunoglobulin heavy chain gene in germline configuration.
AB  - Four childhood acute leukemias with morphological, cytochemical and immunological
      characteristics correlating to precursor B lymphocyte and with germline
      configuration of the immunoglobulin heavy chain joining region were studied for
      the organization of the C mu segment. Two of the four lymphoblast samples
      retained the germline configuration of both JH and C mu regions. The other two
      samples showed delection of the entire JH region resulting in the rearrangement
      of the C mu region. In contrast to patients with C mu rearrangement, patients
      with C mu in germline form were not able to achieve complete remission after
      induction therapy. Study of the C mu region in patients with JH segment in
      germline configuration could separate subgroups in childhood precursor B acute
      lymphoblastic leukemia with different prognoses.

PMID- 8750639
TI  - Ocular masquerade syndrome in lymphoid blast crisis of chronic myeloid leukemia.
AB  - A 56-year-old woman presented with CML in lymphoid blast crisis. Complete
      remission with no suggestion of CML was achieved with chemotherapy. Twenty-six
      months later, an isolated ocular anterior chamber relapse of acute leukemia
      presenting as uveitis (ocular masquerade syndrome) was diagnosed and treated with
      radiotherapy. Ten months later, a second ocular relapse in the same location was
      diagnosed and treated with radiotherapy. Two months later, a systemic relapse
      into second chronic phase was diagnosed and is currently being treated with alpha
      interferon. Only one previous case of leukemic hypopyon in CML has been reported.
      This is also the first case of isolated ocular blast crisis relapse in CML to be
      described.

PMID- 8750640
TI  - Complex IgA gammopathy in Gaucher's disease.
AB  - A 55-year-old Jewish patient was simultaneously diagnosed as having Gaucher's
      disease and IgA multiple myeloma. Serum protein electrophoresis and
      immunoelectrophoresis showed two different IgA kappa type monoclonal spikes.
      After four years of observation, a rapid fatal course of disease developed
      together with expression of J chain protein and an additional IgA lambda
      paraprotein. Although dysproteinaemias and multiple myeloma have occasionally
      been reported in Gaucher's patients, such a complex gammopathy has to the best of
      our knowledge not yet been described.

PMID- 8750641
TI  - Unremitting severe autoimmune haemolytic anaemia as a presenting feature of
      Hodgkin's disease with minimum tumour load.
AB  - Two patients are reported who presented with severe autoimmune haemolytic anaemia
      (AIHA) of warm antibody type, with poor response to treatment. Extensive
      investigations failed to find a cause in both cases. In one case therapeutic
      splenectomy, one year after the initial presentation, showed Hodgkin's disease
      (HD) in the spleen but nowhere else. The second patient died of unremitting AIHA
      almost two years after the presentation and HD was found in only one mediastinal
      lymphnode at autopsy. These cases illustrate that a minimum tumour load of HD
      undetectable by the usual investigations can be associated with life-threatening
      AIHA.

PMID- 8750642
TI  - Successful chemotherapy including epirubicin in a pregnant non-Hodgkin's lymphoma
      patient.
AB  - We report a case of non-Hodgkin's lymphoma (NHL) successfully treated with
      combination chemotherapy during pregnancy. The histological diagnosis was large
      cell B-type NHL. Four courses of chemotherapy with epirubicin, vincristine and
      prednisolone were given before delivery. The patient is in complete remission and
      her baby, now four years old, has developed normally. To our knowledge, this is
      the first reported case of epirubicin administration during pregnancy and in
      which chemotherapy was given safely to NHL patients during the second and third
      trimester of pregnancy.

PMID- 8750643
TI  - Multiple myeloma following essential thrombocythemia.
AB  - The association of essential thrombocythemia (ET) and multiple myeloma (MM) is
      exceedingly rare, with only four such cases reported in the literature until now.
      In this paper, a patient is reported who developed IgA-lambda MM more than five
      years after the diagnosis of ET, for which she had received alpha interferon and
      radioactive phosphor (32P). She died shortly afterwards despite melphalan and
      prednisone therapy. In four of the five patients in whom the above association
      has been reported, including the present one, MM appeared some time after ET was
      initially recognized, with three of them having received alkylating drugs as
      their treatment for ET. MM was heterogeneous with respect to the M--component
      type and the clinical course. The possible etiological & pathogenetic link
      between both these entities is discussed.

PMID- 8750644
TI  - Tumor markers in the diagnosis, monitoring and therapy of pancreatic cancer:
      state of the art.
AB  - The present review focuses on the utility of serum tumor markers in screening,
      diagnosis, prognosis and monitoring of pancreatic cancer. Serum determination of
      all tumor markers studied offers no help in screening or early diagnosis of
      pancreatic cancer. For diagnosis, blood group-related antigens, in particular CA
      19-9, are considered the best indicators of this neoplasm. However, as occurs
      with other glycoproteic tumor markers, the circulating levels of CA 19-9 are
      significantly influenced by jaundice, probably because its liver metabolism is
      reduced. Therefore, the finding of elevated CA 19-9 levels in jaundiced patients
      has to be evaluated with caution. Since pancreatic cancer recurrences are not
      susceptible to treatment, the clinical role of widespread use of tumor marker
      determination in follow-up programs is limited and calls for a critical
      evaluation.

PMID- 8750645
TI  - Analysis of the temporal compressibility of breast tumour marker assays:
      development of a "near patient" assay.
AB  - The aim of this study was to investigate whether immunoassays for circulating
      MUC1 antigen in breast cancer could be compressed in time so that serum level
      results would be made available during the time of the patient's visit to clinic.
      Two assays were used: -The EMCA (Euro DPC) is a liquid phase immunoassay and the
      ELSA CA15-3 (CIS) is a double determinant solid phase immunoradiometric assay.
      The effects of shortened incubation times were investigated by assaying standards
      and unknown samples and comparing the results with those using the standard kit
      protocols. The binding kinetics of the monoclonal antibodies employed in the
      assays were analysed separately. We conclude that the EMCA assay can be shortened
      to 35 min and we have attributed this to the fast binding kinetics inherent in a
      liquid phase assay. This shortened assay may produce the basis for a useful "near
      patient" assay. By comparison, the solid phase ELSA CA15-3 assay cannot be
      compressed without loss in assay performance.

PMID- 8750646
TI  - Intraoperative fall in plasma levels of intact parathyroid hormone in patients
      undergoing parathyroid adenomectomy.
AB  - Intraoperative measurement of intact parathyroid hormone (PTH) can be used to
      evaluate the success of parathyroid surgery in primary hyperparathyroidism
      associated with parathyroid adenoma. To evaluate this approach we used a modified
      immunoradiometric assay (IRMA) to study the kinetic patterns of circulating PTH
      disappearance in 13 patients undergoing adenomectomy for single adenoma. The
      rapid and the standard assay for PTH measurement in plasma were used and
      compared. The two methods showed a highly significant correlation (r = 0.995; p <
      0.0001). We reported a decrease in PTH to 18.2 +/- 2.30 (mean +/- SEM) from
      baseline values at 15 minutes after successful parathyroid adenomectomy in the 13
      patients. The biphasic pattern of serum PTH clearance was calculated in 8 of the
      studied patients with a fast phase showing a half-life (T1/2) of 3.99 (SEM 0.464)
      minutes and a slow phase with a T1/2 of 91.0 (SEM 33.6) minutes. Half the amount
      of the basal values was reached between 4 and 9 minutes. Our study concludes that
      the modified IRMA for intraoperative measurement is feasible, reliable and
      sufficiently precise for low hormone values. Since it may yield information on
      the half-life of PTH in the circulation, it may play a role in the surgical
      guidance for total exeresis of hyperfunctioning tissue.

PMID- 8750647
TI  - Detection of Epstein-Barr virus genome in squamous cell carcinomas of the larynx.
AB  - Epstein-Barr virus (EBV) is a B-lymphotropic virus with a tumorigenic potential.
      EBV infection has been recognized as the main cause of nasopharyngeal carcinoma
      and Burkitt's lymphoma. The aim of our study was to determine the incidence of
      EBV in squamous cell carcinomas of the larynx. We employed for our analysis a
      sensitive polymerase chain reaction (PCR) assay, followed by restriction fragment
      length polymorphism (RFLP) for further confirmation of the specificity of the PCR
      amplification reaction. Our analysis revealed that 9 of 27 (33%) specimens
      harbored the EBV genome in the tumor tissue while only 4 (15%) specimens from
      adjacent normal tissue exhibited evidence of EBV infection. Three were EBV
      positive for both normal and tumor tissue. No association has been found with
      disease stage, histological differentiation and nodes at pathology. The
      relatively high incidence of EBV in the tumor tissue (33%) of patients with
      laryngeal cancer, as compared to the low (15%) incidence of the virus genome
      detected in the adjacent normal tissue of the patients, indicates a probable role
      of EBV in the development of the disease.

PMID- 8750648
TI  - Growth factors in human ovarian follicle fluid and growth factor receptors in
      granulosa-luteal cells.
AB  - The levels of oestradiol (E2), progesterone (P4), transforming growth factor
      alpha (TGF alpha), transforming growth factor beta 2 (TGF beta 2), insulin-like
      growth factor I (IGF-I), platelet-derived growth factor AB (PDGF-AB) and
      epidermal growth factor (EGF) were measured in follicular fluids obtained from
      patients undergoing ovarian stimulation as part of an in vitro fertilisation
      program. Each of the substances was detected in all of the fluid samples tested,
      except TGF alpha (which was detected in 90% of samples tested), PDGF-AB (70%) and
      EGF (2%). Comparisons were made between each of these factors, follicular
      maturity, successful oocyte recovery and the outcome of fertilisation and embryo
      transfer. No statistically significant correlations were found. The presence of
      receptors for EGF, IGF-I and PDGF in extracts from granulosa-luteal cells
      isolated from follicular fluids was detected by means of Western blotting. The co
      localisation of these growth factors and their receptors within the ovarian
      follicle suggests a likely role in control of follicular development.

PMID- 8750649
TI  - Prostate-specific antigen (PSA) and cancer-associated serum antigen (CASA) in
      distinguishing benign and malignant prostate disease.
AB  - The Prostate-Specific Antigen (PSA) and the Cancer-Associated Serum Antigen
      (CASA) assay for the MUC1 mucin were compared in the serum of 303 patients with
      malignant or benign prostatic disease. Using cutpoints of 4, 10, and 20
      micrograms/l, PSA was elevated in 93%, 81%, and 64% of patients with prostate
      cancer (n = 113), with corresponding specificities of 55%, 84%, and 96% in benign
      prostate disease (prostatic hyperplasia or prostatitis, n = 190). Using the
      recommended cutpoint of 4 Units/ml, CASA was elevated in 38% of patients with
      prostate cancer, with a specificity of 91% in benign disease. PSA and CASA showed
      a poor correlation in prostate cancer (r = 0.367) and benign disease (r = 0.158),
      and CASA was elevated in some PSA negative samples. Used together, PSA > or = 20
      micrograms/l and CASA > or = 4 kU/l gave perfect specificity in benign disease,
      with a corresponding sensitivity of 29% (positive and negative predictive values
      of 100% and 70%, respectively). However, this combination gave no improvement
      over the use of PSA alone, with sensitivity 47% when the cutpoint was raised to
      give perfect specificity. These data suggest that CASA is of little use as an
      adjunct to PSA in the differentiation of benign and malignant prostate disease.

PMID- 8750650
TI  - Reliability of volume or age-adjusted prostate specific antigen to improve
      diagnostic accuracy.
AB  - Prostate Specific Antigen (PSA), PSA density, PSA excess, and PSA age-specific
      range have been compared in 331 subjects (35 cancers, 296 benign) with equivocal
      findings at screening by PSA or palpation+transrectal ultrasonography. The
      specificity of PSA using a cut-off of 4 ng/ml was only 0.49. A cutoff of 10 ng/ml
      improved the specificity to 0.88 but the sensitivity decreased from 0.97 to 0.63.
      The sensitivity and specificity for PSA density (cutoff 0.15), PSA excess (cutoff
      -5), and age-specific range were 0.86 and 0.80, 0.80 and 0.82, and 0.91 and 0.67,
      respectively. Avoided benign biopsies vs missed cancers on the basis of PSA
      density, PSA excess and PSA age-specific range would have been 19 and 5, 26 and
      7, and 16 and 3, respectively. Methods adjusting for prostate volume allow a
      better interpretation of PSA values and may reduce the benign biopsy rate, but
      the consequent cost of delayed cancer diagnoses when the choice of biopsy is
      based only on these methods seems unacceptable.

PMID- 8750651
TI  - Third-generation PSA: ultrasensitive or ultraprecise assay?
AB  - The ultrasensitive PSA assay has been recently acknowledged as a useful tool for
      the monitoring of patients prostatectomized for prostatic cancer. We have
      evaluated a commercially available ultrasensitive PSA assay (Immulite Third
      Generation PSA-DPC-Los Angeles CA) in comparison with the routinely used PSA
      (Immulite PSA-DPC-Los Angeles CA). When evaluated with different approaches, the
      analytical sensitivity of ultrasensitive PSA ranged between 0.0029 and 0.0038
      ng/ml. The biological detection limit was 0.0098 ng/ml. Dilution of samples with
      low PSA levels showed a good recovery (from 88 to 113%) up to 1:128 dilution
      factor (final PSA levels ranging from 0.004 to 0.016 ng/ml in different samples).
      The assay precision was excellent in the low dose range, the highest interassay
      interadjustment CV among replicates being 5.84% when assaying serum samples with
      PSA lower than 1.0 ng/ml. Besides its role in the follow-up of prostatectomized
      patients, the evaluated ultrasensitive PSA could be reliably used for the
      detection of clinically meaningful PSA variations in the low dose range, and it
      could therefore be a candidate for the assessment of PSA velocity.

PMID- 8750652
TI  - Impact of kidney and liver metabolism on serum prostate specific antigen levels.

PMID- 8750653
TI  - Prostate specific antigen in non-serum samples from women.

PMID- 8750654
TI  - The natural history of arachnoid cysts: endoscopic and cine-mode MRI evidence of
      a slit-valve mechanism.
AB  - Arachnoid cysts are space-occupying lesions filled with CSF-like content and
      surrounded by a membrane resembling arachnoid matter. They are regarded as a
      development abnormality of the arachnoid, originating from a splitting or
      duplication of this membrane. However, precise etiology and natural history
      remain controversial. Different hypotheses have been developed including agenesis
      of brain structures, arachnoiditis, active fluid secretion, and pulsatile pump.
      We present a review of the literature concerning these items and report one case
      of a suprasellar arachnoid cyst in which a slit-valve mechanism was observed by
      means of cine-mode MRI preoperatively and confirmed during the endoscopic
      intervention.

PMID- 8750655
TI  - Modern management of spinal and spinal cord vascular lesions.
AB  - Spinal arteriovenous shunts affect all age groups from neonates to the elderly in
      connection with different entities. The authors present 7 illustrative cases of
      spinal and spinal cord vascular lesions with different etiology,
      angioarchitecture, symptoms, risks, and prognosis, but similar pathophysiology:
      spinal cord AVM, multifocal AVM with venous impairment, paraspinal arteriovenous
      fistulas in children, spinal dural AV fistula, and an arteriovenous malformation
      of the filum terminale. Therapy was consistent and demonstrated the benefit of
      combined treatment. Specific endovascular embolisation with a permanent liquid
      substance (NBCA) is the method of choice. In 5 of the 7 patients, the
      malformation was completely occluded in one therapeutic session. Two patients
      needed additional embolisation. Systemic or neurological symptoms improved or
      regressed completely in all cases. No patient has had more than 3 sessions of
      endovascular approach. The filum terminale AVM was treated by direct surgery due
      to the risks of endovascular approach. As shown by our observations, venous flow
      in the intrinsic network of the spinal cord is highly sensitive to hemodynamic
      changes. Thus, the hemodynamic balance must be maintained to obtain stable
      embolisation results, particularly if a considerable size reduction of the AV
      shunt has been achieved.

PMID- 8750656
TI  - Pitfalls in the pterional approach to the parasellar area (review).
AB  - The pterional approach is commonly employed in surgery of the anterior
      circulation and upper basilar artery aneurysms, as well as for the tumors of
      orbital, retroorbital, sellar, chiasmatic, subfrontal and prepontine areas and
      lesions around the sella especially for lesions behind the clivus. Also tumors
      arising from the medial sphenoid ridge, the superior orbital fissure, the
      anteromedial temporal surface, or the cavernous sinus region are approached
      through a pterional exposure. The surgical technique is based on the experience,
      training and observation of the neurosurgeon. One technique is not necessarily
      better than another. Regardless of the surgical technique, the end results depend
      on a rigorous, methodical, systematic, and step-by-step approach to the target,
      securing it with minimal injury to surrounding structures. In this study, we have
      analyzed the intraoperative anatomical findings of the Sylvian vein and fissure,
      lenticulostriatal artery, olfactory nerve, and recurrent artery of Heubner and
      showed the surgical pitfalls in 700 patients with different diagnoses that were
      operated on with the pterional approach. The findings were recorded during
      surgical interventions and through the slides and videotapes of the operations.
      Also, we have stressed the preservation of the frontotemporal branch of the
      facial nerve, the delicate retraction of frontal lobe, the cottonoid retraction
      in temporal lobe and the preservation of olfactory nerve functions.

PMID- 8750657
TI  - Surgical pitfalls in pinealoma surgery.
AB  - The author has treated 30 cases of pinealoma by the infratentorial
      supracerebellar approach with the patient in the sitting position. Long-term
      outcome has been excellent in 26 cases, poor in 1, and death in 3 cases.
      Postoperative deaths were due to: (i) high venous pressure in the jugular vein
      caused by a tourniquet placed around the neck to prevent air-embolism, making
      hemostasis more difficulty, (ii) the absence of retraction resulting in a narrow
      surgical field when acute brain swelling developed, and (iii) high coagulation
      and ablation of the precentral cerebellar vein causing diffusion thrombosis of
      deep veins. The details of these cases are presented in this article.

PMID- 8750658
TI  - The radiographic restoration of the ventricular system after third
      ventriculostomy.
AB  - Ten adult patients were treated by third ventriculostomy for idiopathic
      aqueductal stenosis. Idiopathic aqueductal stenosis was diagnosed according to MR
      imaging; aqueductal stenosis secondary to tumor, hemorrhage, and/or infection was
      excluded. Following a third ventriculostomy under a flexible neuroendoscope, all
      patients were reviewed at 1, 3, 6, 12, and 24 months, and MR images with
      ventricular measurements were repeated for evaluation of the radiographic
      restoration of the ventricular system. The ventricular structures arranged in
      order of restoration were the size of the III ventricle, the upward deviation of
      the brain stem, and the size of the lateral ventricle in response to third
      ventriculostomy. The restoration of the whole ventricle steadied within two
      years. Our results contribute new information regarding restoration of the
      ventricular system under aqueductal stenosis and produce evidence that third
      ventriculostomy is a reasonable treatment based upon the patient's physiological
      condition.

PMID- 8750659
TI  - Frameless neuronavigation in modern neurosurgery.
AB  - A fundamental effort in neurosurgery is to reduce surgical trauma.
      Microneurosurgical technique combined with precise localization of lesions, can
      minimize the invasiveness of neurosurgical procedures. This report summarizes the
      utility of frameless neuronavigator systems and examines their value in reducing
      operative invasiveness. The basic principle of neuronavigation is the virtual
      linkage between digitized neuroradiological data and real anatomical structures,
      allowing an excellent three-dimensional orientation by real-time graphic-anatomic
      interaction. As frameless graphic interactive neuronavigation is developed
      further, these devices should become an important component of the modern
      microneurosurgical armamentarium and reduce surgical morbidity.

PMID- 8750660
TI  - Prototype instruments for endoscopic microsurgery: technical note.
AB  - The authors describe a concept of converting microsurgical instruments into
      endoscopes and demonstrate prototype devices. These instruments combine the
      benefits of microsurgery (multiple instruments, tactile feedback, bimanual
      manipulation, magnification) with those of endoscopy (minimally invasiveness,
      indirect line of vision).

PMID- 8750661
TI  - Physiology of food poisoning microorganisms and the major problems in food
      poisoning control.
AB  - There remains considerable public concern regarding the current high level of
      food poisoning disease in Europe and the fact that, year by year, it continues to
      rise rather than fall. At the same time, there are strong and increasing demands
      from consumers for foods that are more convenient, fresher, more natural, less
      heavily processed (e.g. 'REPFEDS' and 'Sous Vide' foods, mildly heated and
      distributed at chill temperatures; Lund and Notermans, 1992), less heavily
      preserved (e.g. less acid, less salt, less sugar; Gould, 1995) and less reliant
      on additive preservatives than hitherto (e.g. sulphite, nitrite, organic acids
      and esters; Russell and Gould, 1991). Most of these trends result in a general
      reduction in the intrinsic preservation of foods. Furthermore, many food
      poisoning microorganisms escape the attention of preservation techniques
      altogether, reaching the consumer more or less directly from contaminated foods,
      most often foods of animal origin. It has therefore been argued that a
      substantial reduction in food poisoning in the near future will be difficult to
      achieve unless we obtain a greatly improved understanding of the physiology of
      the most important target organisms (Knochel and Gould, 1995). This knowledge
      must then be exploited in ways which effectively improve our means for the
      control of these hazards and reduce the risk to the consumer. A three year AAIR
      Concerted Action Programme (PL920630: 'Physiology of Food Poisoning
      Microorganisms') was therefore initiated in 1992 in order to bring together
      research groups working on the physiology and related aspects of food poisoning
      microorganisms. The principal objectives of the programme were: 1. To determine
      the physiological, biochemical and genetical bases of the organisms' survival of
      and responses to food-relevant stresses; 2. to determine the physiological and
      genetical factors influencing infectivity and toxinogenesis; 3. to understand the
      physiological bases of those synergistic systems that are already empirically
      applied or that have future potential; 4. to make a wide range of modern
      techniques in which particular members have expertise more widely available. As
      can be read in the subsequent contributions to this special issue, the area is a
      fruitful one for microbiological research and the Programme has been successful
      in bringing together disparate strands of the topic. It has also highlighted
      areas where this scientific knowledge may be better exploited in improving the
      microbiological safety of foods for the consumer.

PMID- 8750662
TI  - A survey of bacterial toxins involved in food poisoning: a suggestion for
      bacterial food poisoning toxin nomenclature.
AB  - There is at present no accepted nomenclature for bacterial protein toxins,
      although there have been several attempts at dividing them into groups by their
      mode of action. In this paper we will not try to describe all known bacterial
      protein toxins, but concentrate on the toxins involved in food poisoning.
      Although most of these toxins are enterotoxins (protein exotoxins with the site
      of action on the mucosal cells of the intestinal tract) there are also other
      toxins involved in food poisoning, like the neurotoxins. In Table 1 the most
      important food pathogens in Europe are listed. For most, but not all, of these
      food pathogens, toxins are virulence factors. Generally, we divide food poisoning
      into infections and intoxications, where Salmonella spp. and Shigella spp. are
      typical examples of infections and Clostridium botulinum and Staphylococcus
      aureus for intoxications. We consider it better to make four different groups of
      food pathogenic bacteria, according to Table 2. Today the first three groups are
      all defined as infections, although for both group 2 and 3 the bacterium itself
      does not harm the host directly. The bacterium in such locations is like an
      'enterotoxin factory'. The bacteria belonging to group 3 do not even interact
      with the epithelial cells in the intestine, while the bacteria of group 2 must
      colonise the epithelial cells prior to enterotoxin production.

PMID- 8750663
TI  - What problems does the food industry have with the spore-forming pathogens
      Bacillus cereus and Clostridium perfringens?
AB  - Spore-forming bacteria are special problems for the food industry. It is not
      always possible to apply enough heat during food processing to kill spores, thus
      we have to take advantage of knowledge of the spore-formers to control them. For
      the meat industry Clostridium perfringens might become a special problem,
      although this bacterium mainly causes food poisoning through food served in
      restaurants, hospitals or homes for elderly people (Cliver, 1987; Reynolds, 1987;
      Gondrosen et al., 1990). The reason for the food poisoning is always the same:
      meat-containing dishes stored after cooking with insufficient cooling and
      reheating (Granum, 1990). Even though it should be relatively easy to control
      this kind of food poisoning, C. perfringens is still one of the most common
      sources of foodborne diseases. Proper disinfection is necessary to control this
      type of food poisoning, as it is now clear that only kitchen strains of C.
      perfringens are able to produce the large amounts of enterotoxin necessary to
      cause food poisoning (Granum, 1990; Cornillot et al., 1995). Bacillus cereus is
      more difficult to control, specifically in the dairy industry, where it is now
      causing the main problems. Insufficient heating of rice-containing dishes has
      been known to cause B. cereus food poisoning of the emetic kind for a long time
      (Kramer and Gilbert, 1989), but will not be dealt with in this paper. There are
      several reasons for the problems in the dairy industry. First of all it seems to
      be impossible to completely avoid the presence of B. cereus in all milk samples.
      Secondly the spores are very hydrophobic (Husmark, 1993), and will attach to the
      surfaces of the pipelines of the dairy industry, where they might multiply and
      resporulate. A third problem is that pasteurisation heating is insufficient to
      kill the spores, while competition from other vegetative bacteria is eliminated.
      It seems that several B. cereus strains have become psychrotrophic over the
      years, making possible growth at temperatures as low as 4-6 degrees C (Granum et
      al., 1993a). None of the methods used to control hygiene in the dairy industry so
      far are able to control B. cereus. This is a continuously increasing problem for
      the industry but, with emerging knowledge, we should be able to control it. In
      this paper we will discuss the problems the food industry is facing with C.
      perfringens and B. cereus, and how these problems might be solved. We will also
      give our view on how research might ease these problems in the future.

PMID- 8750664
TI  - Emerging pathogens: Aeromonas spp.
AB  - Aeromonas spp. are Gram-negative rods of the family Vibrionaceae. They are normal
      water inhabitants and are part of the regular flora of poiquilotherm and
      homeotherm animals. They can be isolated from many foodstuffs (green vegetables,
      raw milk, ice cream, meat and seafood). Mesophilic Aeromonas spp. have been
      classified following the AeroKey II system (Altwegg et al., 1990; Carnahan et
      al., 1991). The major human diseases caused by Aeromonas spp. can be classified
      in two major groups: septicemia (mainly by strains of A. veronii subsp. sobria
      and A. hydrophila), and gastroenteritis (any mesophilic Aeromonas spp. but
      principally A. hydrophila and A. veronii). Most epidemiological studies have
      shown Aeromonas spp. in stools to be more often associated with diarrhea than
      with the carrier state; an association with the consumption of untreated water
      was also conspicuous. Acute self-limited diarrhea is more frequent in young
      children, in older patients chronic enterocolitis may also be observed. Fever,
      vomiting, and fecal leukocytes or erythrocytes (colitis) may be present (Janda,
      1991). The main putative virulence factors are: exotoxins, endotoxin (LPS),
      presence of S-layers, fimbriae or adhesins and the capacity to form capsules.

PMID- 8750665
TI  - Bacteriocins: modes of action and potentials in food preservation and control of
      food poisoning.
AB  - Lactic acid bacteria (LAB) play an essential role in the majority of food
      fermentations, and a wide variety of strains are routinely employed as starter
      cultures in the manufacture of dairy, meat, vegetable and bakery products. One of
      the most important contributions of these microorganisms is the extended shelf
      life of the fermented product by comparison to that of the raw substrate. Growth
      of spoilage and pathogenic bacteria in these foods is inhibited due to
      competition for nutrients and the presence of starter-derived inhibitors such as
      lactic acid, hydrogen peroxide and bacteriocins (Ray and Daeschel, 1992).
      Bacteriocins, are a heterogenous group of anti-bacterial proteins that vary in
      spectrum of activity, mode of action, molecular weight, genetic origin and
      biochemical properties. Currently, artificial chemical preservatives are employed
      to limit the number of microorganisms capable of growing within foods, but
      increasing consumer awareness of potential health risks associated with some of
      these substances has led researchers to examine the possibility of using
      bacteriocins produced by LAB as biopreservatives. The major classes of
      bacteriocins produced by LAB include: (I) lantibiotics, (II) small heat stable
      peptides, (III) large heat labile proteins, and (IV) complex proteins whose
      activity requires the association of carbohydrate or lipid moieties (Klaenhammer,
      1993). Significantly however, the inhibitory activity of these substances is
      confined to Gram-positive bacteria and inhibition of Gram-negatives by these
      bacteriocins has not been demonstrated, an observation which can be explained by
      a detailed analysis and comparison of the composition of Gram-positive and Gram
      negative bacterial cell walls (Fig. 1). In both types the cytoplasmic membrane
      which forms the border between the cytoplasm and the external environment, is
      surrounded by a layer of peptidoglycan which is significantly thinner in Gram
      negative bacteria than in Gram-positive bacteria. Gram-negative bacteria possess
      an additional layer, the so-called outer membrane which is composed of
      phospholipids, proteins and lipopolysaccharides (LPS), and this membrane is
      impermeable to most molecules. Nevertheless, the presence of porins in this layer
      will allow the free diffusion of molecules with a molecular mass below 600 Da.
      The smallest bacteriocins produced by lactic acid bacteria are approximately 3
      kDa and are thus too large to reach their target, the cytoplasmic membrane
      (Klaenhammer, 1993; Stiles and Hastings, 1991). However, Stevens et al. (1991)
      and Ray (1993) have demonstrated that Salmonella species and other Gram-negative
      bacteria become sensitive to nisin after exposure to treatments that change the
      permeability barrier properties of the outer membrane (see below). This review
      will focus on the mode of action of lantibiotics (class I) and class II LAB
      bacteriocins and their potentials in food preservation and control of food
      poisoning.

PMID- 8750667
TI  - Understanding physical inactivation processes: combined preservation
      opportunities using heat, ultrasound and pressure.

PMID- 8750666
TI  - Salmonella, Campylobacter and Escherichia coli O157:H7 decontamination techniques
      for the future.
AB  - Raw meat, particularly poultry meat, remains an important, and probably the major
      source of human infection with campylobacters and salmonellas. In spite of
      decades of effort it has so far proved extremely difficult to raise food animals
      free of these pathogens. For the foreseeable future, therefore, the most
      effective approach must be to decontaminate the final raw product. In this way
      numbers of these pathogens entering kitchens and commercial food processing
      premises will be reduced substantially, and hence opportunities for cross
      contamination onto ready-to-eat foods or for survival during cooking or other
      processes will be much lower. The ideal method of decontamination will have the
      following attributes: it will not change appearance, smell, taste or nutritional
      properties; it will leave no residues; it will pose no threat to the environment;
      it will encounter no objections from consumers or legislators; it will be cheap
      and convenient to apply; it will improve the shelf life by inactivating spoilage
      organisms as well as pathogens. Various techniques will be listed and their
      potential assessed (see Table 1).

PMID- 8750669
TI  - Physiology of the osmotic stress response in microorganisms.

PMID- 8750668
TI  - Growth/survival of psychrotrophic pathogens on meat packaged under modified
      atmospheres.

PMID- 8750670
TI  - Acid adaptation and food poisoning microorganisms.

PMID- 8750671
TI  - Membranes as a target for stress adaptation.

PMID- 8750672
TI  - The significance of bacteria in stationary phase to food microbiology.

PMID- 8750673
TI  - Yeast cell responses to water potential variations.

PMID- 8750674
TI  - Effect of sporulation temperature on some properties of spores of non-proteolytic
      Clostridium botulinum.

PMID- 8750675
TI  - Submerged bacterial colonies within food and model systems: their growth,
      distribution and interactions.

PMID- 8750676
TI  - Flow cytometry applications in physiological study and detection of foodborne
      microorganisms.

PMID- 8750677
TI  - Seroprevalence of Toxoplasma gondii in cattle, sheep and goats in Iran.
AB  - Serum samples from 2000 cows, 3311 sheep and 638 goats from Iran were examined
      for antibodies to Toxoplasma gondii by use of the latex agglutination (LAT) and
      indirect hemagglutination tests (IHAT). Antibodies to T. gondii were found in
      24.50% sheep and 19.25% of goats. Antibodies to T. gondii were not detected in
      cow sera by LAT and IHAT in 1:8 and 1:64 dilutions of bovine sera, respectively.
      Toxoplasma gondii was not found in tissues of 300 aborted fetuses from cows by
      direct microscopy and bioassay in mice.

PMID- 8750678
TI  - Detection of Cryptosporidium parvum oocysts in faeces: comparison of conventional
      coproscopical methods and the polymerase chain reaction.
AB  - Conventional and coproscopical methods were compared with the polymerase chain
      reaction (PCR) for the detection of Cryptosporidium oocysts in bovine faeces.
      Oocysts were not detected in samples seeded with 10,000 oocysts following formol
      ether sedimentation and examination using auramine phenol (AP) or by
      immunofluorescent (IF) staining. When oocysts were concentrated using sucrose
      flotation the threshold of detection was 4000 oocysts per gram for both staining
      methods. Following salt flotation 4000 oocysts per gram could be reliably
      detected by AP staining but the detection limit was increased to 6000 oocysts per
      gram using IF staining. The recovery of oocysts was significantly less than
      expected for all techniques. A specific PCR coupled with immunomagnetic particle
      separation (IMS) of samples detected five oocysts per ml of diluted faeces, which
      corresponds to 80-90 oocysts per gram. Even allowing for the dilution of formed
      faecal samples, required for IMS, this represents an increase in sensitivity of
      several orders of magnitude over the conventional corpodiagnostic methods.

PMID- 8750679
TI  - Light microscopy diagnosis of Babesia bovis and Babesia bigemina kinetes in the
      haemolymph of artificially infected Boophilus microplus engorged female ticks.
AB  - The length, width and position of the nucleus of Babesia bovis and Babesia
      bigemina kinetes from the haemolymph of Boophilus microplus engorged female ticks
      were recorded. Additionally, the shape of Babesia bovis kinetes were registered
      as curved, semi-curved or straight. To this aim Boophilus microplus tick larvae
      from a colony free of Babesia were fed on splenectomised calves artificially
      infected with either Babesia bovis or Babesia bigemina pathogenic strains. Six
      engorged female ticks showing an infection of at least ten mature kinetes of
      Babesia bovis in a sample of haemolymph 5 days after detachment were also
      monitored 7, 9 and 10 days after collection. The same procedure was followed with
      six engorged female ticks infected with Babesia bigemina. One hundred and twenty
      kinetes of each species of Babesia were evaluated. The mean length +/- standard
      deviation and ranges for Babesia bovis kinetes were 14.30 +/- 0.922 microns and
      11.9-16.3 microns, while the corresponding measures for the kinetes of Babesia
      bigemina were 11.27 +/- 0.900 microns and 9.0-13.1 microns (P < 0.001, t-test).
      The width was 3.33 +/- 0.315 microns, 2.6-4.0 microns for Babesia bovis and 2.24
      +/- 0.287 microns, 1.5-2.8 microns for Babesia bigemina kinetes (P < 0.001). The
      most common position of the nucleus was central for both species of Babesia. A
      total of 58% of Babesia bovis kinetes showed the typical curved tail. No effect
      of time post-collection and individual host ticks in the kinete of Babesia
      bigemina was found while an unexpected influence of individual host tick in the
      width of Babesia bovis kinetes was detected (P < 0.01, analysis of variance). The
      overlap in the sizes of kinetes from both species of Babesia makes it difficult
      to apply the results to ticks of unknown babesial infection status. This finding
      is further complicated by the intra-specific size variations of Babesia kinetes
      from different geographical origins.

PMID- 8750680
TI  - Conservation of merozoite membrane and apical complex B cell epitopes among
      Babesia bigemina and Babesia bovis strains isolated in Brazil.
AB  - Babesia merozoite polypeptides bear surface exposed and neutralization-sensitive
      B cell epitopes and have been shown to induce partial protection against
      experimental challenge. Variation in these epitopes has been examined in a
      limited number of strains. In this study, utilizing strains of Babesia bovis and
      Babesia begemina from Matto Grosso do Sul in Brazil, we examined the conservation
      of epitopes bound by monoclonal antibodies developed against Mexico strains of B.
      bovis and B. bigemina. Apical complex B-cell epitopes, previously shown to be
      species-specific but common among otherwise antigenically distinct strains, were
      also conserved between clones of the Mexico strains and the Matto Grosso do Sul
      strains of each Babesia species. Mexico strain polypeptides bearing these
      epitopes were recognized by sera from cattle infected with the Matto Grosso do
      Sul strains. Two distinct epitopes on the B. bovis neutralization-sensitive
      merozoite surface antigen-1 (MSA-1) were also conserved between the Mexico Mo7
      clone and the Matto Grosso do Sul strain, in contrast to previous studies which
      demonstrated variability among strains. Sera from cattle with B. bovis infections
      naturally acquired in Matto Grosso do Sul bound Mexico Mo7 MSA-1, demonstrating
      that conserved MSA-1 epitopes were recognized by the bovine immune system.
      Similarly, merozoite surface epitopes on the B. bigemina 45 kDa and 55 kDa
      glycoproteins were conserved on the Matto Grosso do Sul strain of B. bigemina.

PMID- 8750681
TI  - Morphology and development of Anaplasma marginale in midgut of engorged female
      ticks of Boophilus microplus.
AB  - Morphology and development of Anaplasma marginale were studied in midgut
      epithelial cells of adult Boophilus microplus females using light and
      transmission electron microscopy. Hemoparasite-free B. microplus larvae were used
      to infest Holstein calves experimentally inoculated with A. marginale. When A.
      marginale parasitemia varied from 0.4% to 4.3%, 140 engorged female ticks were
      collected and kept individually in steel wire tubes and incubated outdoors on
      Brachiaria decumbens grass pasture. Female ticks in groups of 20 were dissected
      14, 19, 26, 33, 40, 47 and 50 days after detachment. Engorged female ticks
      collected from an A. marginale-free calf were kept under the same conditions as
      control ticks. Gut sections of infected and control ticks were processed using
      light and electron microscopy. Infected gut sections were processed by the
      immunocytochemical peroxidase-antiperoxidase technique. Under light microscopy A.
      marginale colonies were found in midgut epithelial cells of engorged B. microplus
      females from 19 days on after detachment from donor calves. Colonies were 6.1
      10.3 microns in diameter, ovoid or irregular and contained round or shaped
      organisms. Two distinct morphological types of colonies (BM1 and BM2) were found.
      BM1 colonies had a dense matrix strongly stained in which organisms were barely
      visible; BM2 had large separated organisms densely stained inside a matrix which
      was lightly stained. A. marginale colonies immunocytochemically stained were
      found in gut tissue sections using light microscopy. Using transmission electron
      microscopy organisms of different morphologies were found in midgut epithelial
      cells of engorged females, suggesting sequential phases of development of A.
      marginale in the vector. Modifications occurred in colonies and in the organisms
      within them. No symbiotic rickettsiae were found in intestinal cells of control
      ticks.

PMID- 8750682
TI  - A mild Theileria parva parasite with potential for immunisation against East
      Coast fever.
AB  - Twenty-three Friesian cattle were inoculated subcutaneously anterior to the left
      prescapular lymph node with 1 ml of a mild isolate of Theileria parva. The cattle
      developed low macroschizont parasitosis but no clinical reaction was observed.
      Thirty-five days later the cattle were grouped into five groups and challenged
      with five different Theileria parva isolates (four cattle-derived Theileria and
      one buffalo-derived Theileria). The cattle were all solidly immune to challenge
      with the cattle-derived Theileria isolates but three out of five of the cattle
      challenged with the buffalo-derived parasite died of theileriosis. All ten non
      immunised control cattle developed severe theileriosis and were treated with
      buparvaquone (Butalex; Pitman-Moore).

PMID- 8750683
TI  - Experimental Taenia solium cysticercosis in pigs: characteristics of the
      infection and antibody response.
AB  - Pigs were infected with taeniid eggs to study the susceptibility to infection and
      reinfection of the animals of mixed breeds and of different ages, the viability
      and death of the metacestodes in the host tissue, and the antibody response which
      accompanies these events. Sixteen pigs were infected with Taenia solium eggs for
      this purpose. At necropsy metacestodes were counted in 2 kg of shoulder muscles
      and classified as vesicular or caseous, and all the metacestodes in brains were
      counted and classified. The results show that pigs inoculated at 49 and 60 days
      of age became infected to different degrees and reacted differently to the
      presence of parasites. In the brain the metacestodes remain viable for longer
      periods than in muscles. Enzyme-linked immunosorbent assay (ELISA) showed a
      significant rise in antibodies after infection, which started to decrease 92 days
      post-infection (p.i.). Pigs with viable cysts remained seropositive up to the end
      of the experiment (281 days p.i.). Antibody levels rose further after reinfection
      or after treatment. The results of Western blot were comparable to those of
      ELISA. Antigens of 13, 14 and 18 kDa were most frequently recognized in early
      infections and then started to decrease 92 days p.i., while the antigens of 42,
      50 and 24 kDa were recognized during later stages of infection (200 days p.i.).
      The results suggest that older animals are more resistant to the infection
      [corrected].

PMID- 8750684
TI  - Residual effect of injectable moxidectin against lungworm and gastrointestinal
      nematodes in calves exposed to high pasture infectivity levels in the
      Netherlands.
AB  - The residual effect of a 0.2 mg kg-1 injectable formulation of moxidectin against
      lungworm and gastrointestinal nematodes in cattle was studied in a grazing
      experiment in the Netherlands. Five groups of four calves were grazed between May
      and October 1991 and one similar group was used as permanently housed control
      group for the evaluation of the development of immunity against lungworm by
      challenge infections with 5000 larvae of all six groups. The main parameter used
      to determine the residual effect for lungworm was faecal larval counts.
      Additional information was derived from pasture larval counts, enzyme-linked
      immunosorbent assay (ELISA), respiration frequency, coughing score and,
      particularly for evaluating development of immunity, worm counts. For
      gastrointestinal nematode infections faecal egg counts and larval differentiation
      of faecal cultures were the main parameters used. Pasture larval counts and an
      ELISA for Ostertagia and Cooperia were used as additional parameters. In three
      treated groups lungworm larvae (re)appeared in the faeces after 67, 95 and 119
      days, respectively. This implies that a 100% residual effect did not last longer
      than 67-21 = 46 days. The treated group with patency starting on Day 95 was
      exposed to extremely high infection pressure and the ELISA indicated some host
      parasite interactions from 2-4 weeks after treatment. Thus some interaction
      between moxidectin treatment and high infection pressure delayed the onset of
      patency in comparison to another treated group under much lower infection
      pressure. In all treated groups, including the one under high infection pressure,
      lungworm disease was prevented and the worm counts demonstrated development of
      immunity. In contrast, severe lungworm disease occurred in two control groups
      grazing together with the 'high infection pressure' treated group. The faecal egg
      counts and differentiation of larvae from faecal cultures demonstrated a 100%
      residual effect of at least 3 weeks and indicated a high residual effect of
      approximately 5 weeks against Ostertagia. Moxidectin suppressed Cooperia faecal
      egg counts for over 98% and the results indicated a more than 95% residual effect
      on faecal egg output during 2-3 weeks. The ELISA results were indicative for a
      delay of 2 weeks in the acquisition of gastrointestinal nematode infections
      following moxidectin treatment.

PMID- 8750685
TI  - In vitro screening of Haemonchus contortus third stage larvae for ivermectin
      resistance.
AB  - The indiscriminate repeated use of ivermectin has resulted in the emergence of
      ivermectin resistant field strains of Haemonchus contortus in sheep in South
      Africa. There is a need for a rapid and cost effective in vitro test to detect
      such strains. Infective H contortus larvae known to be resistant to ivermectin,
      were incubated in vitro in a diluted concentration of the drug. Subsequently
      their ability to migrate was compared with that of larvae of isolates known to be
      susceptible to ivermectin. The criterion used to determine resistance was the
      ability of the larvae to migrate out of gelled agar after exposure to ivermectin
      using diluted propylene glycol as the control compound. The results obtained by
      this technique confirmed the results obtained with critical controlled tests;
      significant differences between the ivermectin sensitive and resistant isolates
      were demonstrated, thereby confirming that this in vitro technique may be used as
      a screening method to identify ivermectin resistant isolates of H. contortus.

PMID- 8750686
TI  - Epidemiological aspects of lungworm infections of goats in Morocco.
AB  - The results of a survey of lungworm infections in goats in the Middle Atlas and
      Rabat areas in Morocco during 1990-1992 are reported. Five species were recorded:
      Dictyocaulus filaria, Protostrongylus rufescens, Cystocaulus ocreatus, Muellerius
      capillaris and Neostrongylus linearis. The parasitological profile of
      protostrongylid species was represented by Muellerius (69-78%), Protostrongylus
      (16-25%) and Cystocaulus (5-6%) in the Rabat and Middle Atlas areas.
      Neostrongylus was virtually non-existent (under 1%) in both regions. Multigeneric
      infection involving several species of lungworms reached 54% in Rabat and 88% in
      Middle Atlas. Dictyocaulus infection of goats does not appear to be a serious
      problem. Infection rates of 40% and 50%, and average worm burdens of three and
      five worms per kid and adult goat were recorded in autumn in the Rabat area. A
      similar pattern was noted in Middle Atlas. In contrast, the incidence of small
      lungworm infections in goats is widespread at levels likely to be of economic
      significance. The level of infection was considerably higher than the
      Dictyocaulus infection and the infection rate was virtually 100% in both age
      groups in the two areas. The overall worm burdens averaged 77.03 +/- 22.6
      parasites per adult goat and 44.16 +/- 16.3 per kid in the Rabat area, whereas
      the corresponding figures in Middle Atlas were 51.48 +/- 16.65 and 34.06 +/- 2.69
      worms. The periods of high risk of infection by small lungworms were autumn,
      early winter and late spring-early summer. However, the heaviest infection by
      adult worms and the highest larval excretion were observed in late autumn and
      winter when molluscs were heavily infected. The periparturient period seemed to
      exert a positive influence on protostrongylid larval production. The output of
      first stage larvae (L1) of lungworms was significantly higher in goats than in
      sheep. Thus, goats may play a greater role in pasture contamination. The
      epidemiological factors influencing the seasonal fluctuations of lungworms are
      discussed and a timetable of recommended treatments is suggested.

PMID- 8750687
TI  - Involvement of excretion-secretion products from Fasciola hepatica inducing
      suppression of the cellular immune responses.
AB  - Normal rats i.p. injected with Fasciola hepatica excretor-secretor antigen (ESA)
      induced a population of spleen mononuclear (SpM) cells, which suppressed the
      delayed type hypersensitivity (DTH) response to parasite antigens as well as to
      non-related antigens (human serum albumin) by adoptive transfer. A similar effect
      was observed when the cell transfer was performed with SpM cells non-adherent to
      nylon wool. The DTH was not modified by cells transfer adherent to nylon wool in
      syngeneic receptor animals. The observed suppression depended on the
      concentration and inoculation moment of the antigen; 1.8 mg of protein ESA being
      enough to suppress the DTH response at the different days studied, before and
      after immunization with whole F. hepatica antigens. A marked suppression was
      observed when ESA was injected on day 7 pre-immunization. On the other hand,
      inoculation of ESA treated with 0.01 M sodium periodate (carbohydrate oxidant)
      diminished the suppressor effect found after the native ESA inoculation,
      indicating participation of ESA glucidic components in induced suppression.
      Inoculation of ESA fractions obtained from polyacrylamide gel elution with
      different MW range, showed that components between 12 and 23 kDa actively induced
      suppression to the DTH response to parasite antigens.

PMID- 8750688
TI  - Study on a new egg count technique for Macracanthorhynchus hirudinaceus and
      Ascaris suum.
AB  - This paper deals with a new egg count technique for Macracanthorhynchus
      hirudinaceus and Ascaris suum. The making of the new counter and the operation
      are described. The eggs of M. hirudinaceus in the upper, the middle and the lower
      levels of the sediment from swine feces were counted by the new egg count
      technique and the numbers of the eggs in the sedimentary liquids diluted two,
      four, six, eight and ten times were nearly similar. This indicates that the eggs
      dispersed evenly in the sediment and that the new technique is reliable.
      Comparison between the new technique and the McMaster technique shows that the
      number of the eggs counted by the new technique is more than that by the McMaster
      technique. The result show that the new technique has advantages because it
      requires only simple tools, water for flotation and a shorter time of operation.

PMID- 8750689
TI  - Demonstration of vertical transmission of Cowdria ruminantium, the causative
      agent of heartwater, from cows to their calves.
AB  - One of the most important questions about the epidemiology of heartwater in the
      field is how Cowdria ruminatium is transmitted within vertebrate host
      populations. In this study vertical transmission of C. ruminantium from cows to
      their calves was demonstrated. Twelve mixed-breed calves, born to dams living in
      a heartwater-endemic area of Zimbabwe, were tested post-natally for the presence
      of C. ruminantium. Vertical transmission was demonstrated to occur under natural
      field conditions using tests in which uninfected laboratory-reared Amblyomma
      ticks were fed on neonatal calves and subsequently either fed on, or inoculated
      into, susceptible small ruminants or tested by a polymerase chain reaction (PCR)
      assay. Prior to natural Amblyomma tick infestation, C. ruminantium infection in 5
      of the 12 calves was confirmed by tick transmission to small ruminants and 11 of
      the 12 calves tested positive based on PCR analysis of ticks fed on them. The
      role of colostral cells, as one mode of infection, was demonstrated by the
      transmission of C. ruminantium to three out of five goats inoculated
      intravenously with viable colostral cells collected from dams living in a
      heartwater-endemic area. The significance of vertical transmission is presented
      in relation to the epidemiology and control of heartwater.

PMID- 8750690
TI  - Colostrum from dams living in a heartwater-endemic area influences calfhood
      immunity to Cowdria ruminantium.
AB  - Two studies were carried out to determine whether colostrum from dams living in a
      heartwater-endemic area has an influence on calfhood immunity to Cowdria
      ruminantium infection. The initial study was conducted using Friesian calves
      originating from a heartwater-free herd. Experimental groups consisted of calves
      receiving colostrum from dams living in a heartwater-endemic area and known to be
      exposed to C. ruminantium (as determined by the indirect fluorescent antibody
      test) and calves receiving colostrum from dams located in a heartwater-free area.
      All calves were challenged at 3 days of age with a homologous C. ruminantium
      blood stabilate originating from the same area as the endemic colostrum. A
      significant difference in both the intensity of clinical reactions and percentage
      of fatal heartwater cases was noted between the two groups of calves. Three of
      the five calves receiving the colostrum free of C. ruminantium-specific
      antibodies succumbed to challenge, whereas none of the five calves receiving the
      colostrum from the heartwater-endemic area showed any clinical reactions. A
      second similar study was carried out using 12 mixed breed calves born in a
      heartwater-endemic area of Zimbabwe. The results from this study supported the
      findings of the first. The significant role of colostrum in calfhood immunity to
      C. ruminantium infection is discussed in relation to the epidemiology and control
      of heartwater.

PMID- 8750691
TI  - Prevalence of sarcoptic mange in fattening pigs sacrificed in a slaughterhouse of
      northeastern Spain.
AB  - A study was conducted in fattening pigs from NE Spain to determine the prevalence
      of sarcoptic mange. Pigs were sacrificed in a slaughterhouse in the province of
      Barcelona (Catalonia, NE Spain) in November 1990, April 1991, and October 1991.
      From 7906 pigs slaughtered on those dates, 818 ear scrapings were taken. The
      survey results indicate that 276 (33.7%) of 818 pigs sampled from 58 (86.6%) of
      67 herds were positive for Sarcoptes scabiei (De Geer). The presence of Sarcoptes
      induced skin lesions was examined in 816 pigs. Of the 660 pigs showing skin
      lesions, 244 (37.0%) were positive for mites. A sucrose flotation-concentration
      method was more effective than a direct examination technique to detect S.
      scabiei mites.

PMID- 8750692
TI  - Comparative evaluation of agar gel precipitation, counterimmunoelectrophoresis
      and passive haemagglutination tests for the diagnosis of Dicrocoelium dendriticum
      infection in sheep and goats.
AB  - The sensitivity and specificity of the agar gel precipitation test (AGPT),
      counter immunoelectrophoresis (CIEP) and passive haemagglutination test (PHT)
      were evaluated for the diagnosis of Dicrocoelium dendriticum infection in
      naturally infected sheep and goats. Two hundred and forty five sheep and goat
      sera samples were tested using phosphate buffered saline, pH 7.2 extracted adult
      fluke antigen. CIEP detected 69.8% of the infected animals and was found to be
      the most sensitive, followed by PHT which detected 50.0% of the infected sheep
      and goats. AGPT was found to be the least sensitive, detecting only 23.8% of the
      infected animals. The specificity of

PMID- 8750693
TI  - Worm establishment and egg production of Schistosoma japonicum in pigs infected
      by percutaneous methods or intramuscular injection.
AB  - Worm establishment and egg production were compared in Landrace/Yorkshire
      crossbred pigs infected with Schistosoma japonicum using 3 different infection
      techniques. S. japonicum worm establishment and overall egg production following
      intramuscular injection of cercariae suspended in Iscove's medium exceeded that
      in pigs infected by the leg immersion or the coverslip percutaneous technique.
      However, the egg production per mature female was similar for all three infection
      methods. The results support the use of intramuscular injection of medium
      suspended cercariae as an effective, safe, rapid and convenient infection method
      for studies on the population biology of S. japonicum in pigs when dermal
      cercarial penetration is not required.

PMID- 8750694
TI  - Efficacy of albendazole and fenbendazole against Giardia infection in cattle.
AB  - Efficacies of albendazole and fenbendazole in suppressing Giardia cyst output of
      infected calves were evaluated in two clinical trials. In the first trial, 18
      naturally infected calves were allocated to an untreated control group (n = 9)
      and an albendazole-treated group (n = 9). Calves in the treated group were given
      20 mg/kg-1 oral albendazole once daily for 3 days. Compared to controls, treated
      calves showed 98.5%, 97.6% and 90.8% reductions in cysts per gram of feces (cpg)
      1, 2 and 6 weeks respectively after the start of treatment. In a second trial, 13
      infected calves were allocated to an untreated control group (n = 6) and a
      fenbendazole-treated group (n = 7). Calves in the treated group were given 10 mg
      kg-1 fenbendazole orally twice daily for 3 days. Compared to the control group,
      treatments reduced cpg counts by 100%, 98.5% and 59.5% 1, 2, and 3 weeks
      respectively after the start of treatment. Both albendazole and fenbendazole
      appeared to be effective in suppressing cyst excretion by Giardia-infected
      calves.

PMID- 8750695
TI  - Pneumonia in cats caused by Pneumocystis carinii purified from mouse lungs.
AB  - Fourteen mice trapped in or near houses were infected with Pneumocystis carinii
      and the establishment of pneumonia was helped by injecting with cortisone acetate
      for 6 weeks. Then 16 cats were infected with P. carinii by injection of lung
      homogenate from the mice which contained from 1.3 x 10(5) to 2.6 x 10(5) P.
      carinii cysts. The infection resulted in severe cough and tachypnea in Cats 1-8
      injected with cortisone acetate, and a subclinical infection in Cats 9-16. In
      Cats 1-8, the main pathological finding was typical P. carinii pneumonia, but
      there only was slight swelling of the lungs in Cats 9-16.

PMID- 8750696
TI  - L-Arginine reverses the abolition of hypovolaemic decompensation by N-nitro-L
      arginine methyl ester and naloxone in conscious rabbits.
AB  - Graded caval occlusion in conscious rabbits caused a biphasic haemodynamic
      response. Phase I was characterized by a fall in systemic vascular conductance so
      that arterial pressure was maintained. When cardiac output had fallen to 65 +/-
      2% of its baseline level, phase II supervened. During phase II, conductance rose
      abruptly and arterial pressure fell to a life-threatening level (< or = 40 mm
      Hg). Fourth ventricular administration of either N-nitro-L-arginine methyl ester
      or naloxone prevented the occurrence of phase II. Fourth ventricular
      administration of L-arginine had no effect on the response to graded caval
      occlusion but was able to reverse the phase II blocking action of N-nitro-L
      arginine methyl ester and naloxone. It is concluded that central nitrergic and
      opioid mechanisms interact to cause the vasodilatation characteristic of the
      decompensatory phase II of the cardiovascular response to acute hypovolaemia.

PMID- 8750697
TI  - Protective effect of cystathionine on acute gastric mucosal injury induced by
      ischemia-reperfusion in rats.
AB  - We studied the protective effect of cystathionine on acute gastric mucosal injury
      induced by ischemia-reperfusion in rats. Under pentobarbital anesthesia, the
      celiac artery was clamped for 30 min and reperfused. Sixty minutes after the
      reperfusion, the total area of erosions and thiobarbituric acid-reactive
      substances in the stomach, as an index of lipid peroxidation, were measured and
      compared between control and cystathionine-treated groups. Intraperitoneal
      administration of cystathionine (1-20 mg/kg) 10 min before the ischemia
      significantly reduced both the total area of erosions and the level of
      thiobarbituric acid-reactive substances. When cystathionine (10 mg/kg) was
      administered orally, the significant reductions in the total area of erosions and
      level of thiobarbituric acid-reactive substances were also observed. There was a
      good correlation between the total area of erosions and the level of
      thiobarbituric acid-reactive substances. Cystathionine did not affect blood flow
      during ischemia-reperfusion. These results indicate that the protective effect of
      cystathionine on acute gastric mucosal injury induced by ischemia-reperfusion may
      be due to the scavenging action against superoxide radicals in vivo.

PMID- 8750698
TI  - Effects of repeated administration of selective adenosine A1 and A2A receptor
      agonists on pentylenetetrazole-induced convulsions in the rat.
AB  - The protective effects of the selective adenosine A1 receptor agonist 2-chloro
      N(6)-cyclopentyladenosine (CCPA), the selective adenosine A2A receptor agonist, 2
      hexynyl-5'-N-ethylcarboxamidoadenosine (2HE-NECA), and the non-selective agonist,
      5'-N-ethylcarboxamidoadenosine (NECA) were studied against lethal seizures
      induced by intraperitoneal (i.p.) injection of pentylenetetrazole (80 mg/kg). In
      acute studies there was a dose-dependent reduction of lethal seizures, as shown
      by the low dose's protecting 50% of animals (PD50): 0.11, 0.05 and 0.05 mg/kg
      i.p. for CCPA, 2HE-NECA and NECA, respectively. In the repeated administration
      studies the animals received either vehicle or drug i.p. twice daily for 12 days.
      The drug doses were twice the PD50 value: 0.3 mg/kg for CCPA or 0.1 mg/kg for
      both 2HE-NECA and NECA. 2HE-NECA and NECA maintained their protective activity
      against pentylenetetrazole-induced seizures (63% or 60% vs. 60% or 58% in acute
      studies, respectively). Conversely, repeated treatment with CCPA resulted in a
      marked decrease of its effects (67% vs. 30% in acute studies; P < 0.05). The data
      indicate that in addition to adenosine A1 the A2A receptors also appear to be
      involved in the protection from seizures. The anticonvulsant effects induced by
      repeated stimulation of adenosine A1 receptors are subject to tolerance, whereas
      effects depending on adenosine A2A receptor activation are maintained.

PMID- 8750699
TI  - Neuropeptide Y is a vasoconstrictor and adrenergic modulator in the hamster
      microcirculation by acting on neuropeptide Y1 and Y2 receptors.
AB  - The microvascular effects of neuropeptide Y, and two analogs with preferential
      affinity for different neuropeptide Y receptor subtypes, were assessed by
      intravital microscopy on the hamster cheek pouch. The interaction of neuropeptide
      Y and its analogs with noradrenaline was also studied. Superfusion with 0.1-300
      nM neuropeptide Y caused a concentration-dependent reduction in microvascular
      conductance that was paralleled by reductions in arteriolar and venular
      diameters. These effects of neuropeptide Y were equipotent with noradrenaline,
      but slower to develop and longer-lasting than that of noradrenaline. Neuropeptide
      Y did not affect permeability to macromolecules, as measured by extravasation of
      fluorescent dextran. The neuropeptide Y Y1 receptor agonist,
      [Leu31,Pro34]neuropeptide Y, mimicked neuropeptide Y with similar potency but
      shorter duration, while neuropeptide Y-(13-36), a neuropeptide Y Y2 receptor
      agonist, was at least 10-fold less potent than neuropeptide Y to induce a delayed
      and prolonged reduction in microvascular conductance. The joint superfusion of 1
      nM neuropeptide Y plus 0.1 mu M noradrenaline did not cause synergism, nor even
      summation of effects, but reduced the contractile effect of noradrenaline. No
      synergism was observed after a 10 min priming with 1 nM neuropeptide Y, followed
      by its joint application with 0.1 mu M noradrenaline, but a significant
      vasodilation and hyperemia ensued upon stopping noradrenaline application.
      Priming with 1 nM [Leu31,Pro34]neuropeptide Y prolonged noradrenaline
      vasoconstriction without evidence of hyperemia. In contrast, priming with 1 nM
      neuropeptide Y-(13-36) significantly antagonized noradrenaline vasoconstriction.
      These findings indicate that both neuropeptide Y receptor subtypes are present in
      arterioles and venules of the hamster, and suggest that their activation with
      neuropeptide Y induces a rapid (Y1 receptor subtype activation) and a delayed (Y2
      receptor subtype activation) vasocontractile response. The interaction with
      noradrenaline is complex, without evidence for synergism, but neuropeptide Y Y2
      receptor activation seems to antagonize noradrenaline and/or to facilitate auto
      regulatory vasodilation after the catecholamine-induced vasoconstriction.

PMID- 8750700
TI  - Metabotropic glutamate group II receptors are responsible for the depression of
      synaptic transmission induced by ACPD in the dentate gyrus.
AB  - The functional role of metabotropic glutamate (mGlu) receptors in the rat dentate
      gyrus was investigated. By using extracellular recording techniques in slices, it
      was found that the depression induced by the mGlu receptor agonist (1S,3R)-1
      amino-cyclopentane-1,3-dicarboxylate (ACPD) was mediated through the mGlu group
      II receptors. The mGlu receptor antagonist alpha-methyl-4-carboxyphenylglycine
      (MCPG) (500 mu M), active at group I and group II subtype receptors, was
      effective in antagonizing the ACPD (30 mu M) - induced depression of the
      excitatory field potentials. An antagonist selective for group I, (S)-4
      carboxyphenylglycine (4CPG), did not block the effects induced by ACPD, but by
      itself produced a dose-dependent depression of the field potentials. This ACPD
      like effect shown at high concentrations of 4CPG (300 mu M) is explained by its
      group II receptor agonistic properties and was blocked by bath application of
      MCPG (500 mu M). A selective agonist of group I, (S)-3-hydroxyphenylglycine (3
      HPG), did not cause any depression of synaptic transmission. However, the
      selective mGlu group II receptor agonist, (2S,3S,4S)-alpha
      (carboxycyclopropyl)glycine (L-CCG-I), induced a marked dose-dependent depression
      and its action was blocked by MCPG (500 mu M). Furthermore, the selective mGlu
      group III receptor antagonist, alpha-methyl-L-2-amino-4-phosphonobutyrate (MAP4)
      (500 mu M), was not able to antagonize the depression induced by ACPD (30 mu M),
      but was effective in blocking the action induced by the selective mGlu group III
      agonist, L-2-amino-4-phosphonobutyrate (L-AP4) (100 mu M). These results indicate
      that mGlu group II receptors, but not groups I or III, are involved in the
      depression of synaptic transmission in the dentate area of the hippocampus
      induced by ACPD.

PMID- 8750701
TI  - GYKI 52466 and related 2,3-benzodiazepines as anticonvulsant agents in DBA/2
      mice.
AB  - The behavioural and anticonvulsant effects of several 1-aryl-3,5-dihydro-4H-2,3
      benzodiazepin-4-ones (2,3-BZs) and of 11b-aryl-7,11-dihydro-3
      phenyl[1,2,4]oxadiazolo[5,4-a][2,3]benz odiazepin-6-ones (2,3-OBZs) were studied
      after intraperitoneal (i.p.) administration in DBA/2 mice, a strain genetically
      susceptible to sound-induced seizures. The seizures were evoked by means of
      auditory stimulation (109 dB, 12-16 kHz) in animals placed singly under a
      hemispheric Perspex dome. The 2,3-benzodiazepines studied after 30 min
      pretreatment were generally less potent than the related derivative 1-(4
      aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride
      (GYKI 52466) except 3,5-dihydro-7,8-dimethoxy-1-phenyl-4H-2,3-benzodiazepin-4-one
      (2,3-BZ-2) and 2,3-BZ-2M (3-methyl derivative of 2,3-BZ-2) which showed
      comparable activity. Thirty minutes after i.p. administration of 2,3
      benzodiazepines, the rank order of potency for anticonvulsant activity against
      clonus was 2,3-BZ-2 > GYKI 52466 > 2,3-BZ-2M > 2,3-BZ-1 > 2,3-BZ-3, > 2,3-OBZ-1,
      > 2,3-OBZ-2 2,3-OBZ-3. The intracerebroventricular (i.c.v.) injection of
      aniracetam on it own (12.5 - 100 nmol/mouse) had no convulsant activity, but it
      reversed the anticonvulsant effects of some 2,3-benzodiazepines. In particular,
      the pharmacological actions of GYKI 52466, 2,3-BZ-2 and 2,3-BZ-2M, which proved
      to be the most potent 2,3-benzodiazepine derivatives as anticonvulsants, were
      significantly reduced by an i.c.v. pretreatment with aniracetam (50 nmol/mouse).
      Concomitant treatment with aniracetam (50 nmol/mouse) shifted to the right the
      dose-response curves and significantly increased the ED50 values for GYKI 52466,
      2,3-BZ-2 and 2,3-BZ-2M. After 30 min pretreatment 2,3-BZ-2 showed a similar
      potency to GYKI 52466 in antagonizing seizures induced by i.c.v. administration
      of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), thus
      suggesting a clear involvement of AMPA receptors in the anticonvulsant activity
      of these compounds. In addition, 2,3-BZ-2 and 2,3-BZ-2M showed anticonvulsant
      properties longer lasting than GYKI 52466.

PMID- 8750702
TI  - Chloroethylclonidine increases the incidence of lethal arrhythmias during
      coronary occlusion in anesthetized dogs.
AB  - We studied the role of alpha1-adrenoceptors in the modulation of ventricular
      tachycardia and fibrillation in chloralose-anesthetized dogs subjected to 30 min
      left anterior descending coronary artery occlusion. Study groups were control,
      and those treated with the alpha1-adrenoceptor-subtype blockers WB4101 (0.5 mg/kg
      i.v.) or chloroethylclonidine (1.9 mg/kg i.v.). For the first set of experiments
      all animals were in sinus rhythm and heart rate was slower in the
      chloroethylclonidine-pretreated animals than the WB4101-treated group (P < 0.05).
      During occlusion, ventricular tachycardia and ventricular fibrillation incidence
      did not differ among control, WB4101 or chloroethylclonidine (3 dogs with
      ventricular fibrillation in each group and 0, 2 and 3 dogs respectively with
      ventricular tachycardia), but ventricular premature depolarizations were
      significantly reduced by both interventions, and nonsustained ventricular
      tachycardia was suppressed by WB4101. In a second set of experiments, animals
      were atrially paced at a cycle length of 300 ms, and divided into control, WB4101
      treated or chloroethylclonidine-treated, as above. Here, 9/10
      chloroethylclonidine-treated animals developed ventricular tachycardia and
      fibrillation during occlusion, whereas only 4/10 controls and 4/10 WB4101-treated
      animals did so (P < 0.05). In conclusion, during sinus rhythm, both types of
      alpha1-adrenoceptor subtype blockade significantly suppressed ventricular
      premature depolarizations and neither affected ventricular tachycardia and
      fibrillation. In contrast, when heart rate was held constant,
      chloroethylclonidine clearly enhanced the occurrence of ventricular fibrillation
      during occlusion. These results suggest the alpha1-adrenoceptor subtype blocked
      by chloroethylclonidine, but not that blocked by WB4101, is capable of increasing
      the incidence of lethal arrhythmias that occur at rapid atrial rates during
      ischemia.

PMID- 8750703
TI  - In vitro pharmacology of an angiotensin AT1 receptor antagonist with balanced
      affinity for AT2 receptors.
AB  - L-163,017 (6-[benzoylamino]-7-methyl-2-propyl-3-[[2'-(N-(3-methyl-1-butoxy)
      carbonylaminosulfonyl) [1,1']-biphenyl-4-yl]methyl]-3H-imidazo[4,5-b]pyridine)
      inhibited specific 125I-[Sar1, Ile8]angiotensin II binding to angiotensin AT1
      receptor (Ki = 0.11-0.20 nM) in rabbit aorta, rat adrenal and human angiotensin
      AT1 receptor in CHO (Chinese hamster ovary transformed) cells and to AT2 receptor
      (Ki = 0.14-0.23 nM) in rat adrenal and brain receptors. L-163,017 also had a high
      affinity in the presence of bovine serum albumin (2 mg/ml), for angiotensin AT1
      and AT2 receptors on human adrenal (Ki 3.9 and 4.3 nM), aorta (Ki 0.45 and 0.96
      nM) and kidney (Ki 3.6 and 2.3 nM). The much higher Ki values in human tissues
      were likely due to the presence of bovine serum albumin in the binding assay
      buffer since L-163,017 had Ki values of 0.13 +/- 0.04 and 2.0 +/- 0.04 nM in the
      absence and presence of bovine serum albumin, respectively, in inhibiting 125I
      [Sar1,Ile8]angiotensin II binding to angiotensin AT1 receptor in rat adrenal
      membranes. Scatchard analysis of 125I-[Sar1,Ile8]angiotensin II binding in the
      presence of bovine serum albumin (2 mg/ml) in rabbit aorta and bovine cerebellum
      indicated a competitive interaction of L-163,017 with angiotensin AT1 and AT2
      receptors (Ki values 2.5 and 2.1 nM respectively). L-163,017 inhibited
      angiotensin II-induced aldosterone release in rat adrenal demonstrating that L
      163,017 acted as a competitive antagonist (pA2 = 9.9) and lacked agonist
      activity. L-163,017 also inhibited angiotensin II responses in rat vascular
      tissues. The specificity of L-163,017 was shown by its lack of activity on the
      above functional responses produced by other agonists and in several binding
      assays.

PMID- 8750704
TI  - In vivo pharmacology of an angiotensin AT1 receptor antagonist with balanced
      affinity for AT2 receptors.
AB  - L-163,017 (6-[benzoylamino]-7-methyl-2-propyl-3-[[2'-(N-(3-methyl-1-butoxy)
      carbonylaminosulfonyl)[1,1']-biphenyl-4-yl]methyl]-3H-imidazo[4,5- b]pyridine) is
      a potent, orally active, nonpeptide angiotensin II receptor antagonist. Conscious
      rats and dogs were dosed p.o. and i.v.; in both species the plasma bioequivalents
      are similar at the angiotensin AT1 and AT2 receptor sites indicating balanced
      activity is maintained in vivo. L-163,017 prevents the pressor response to
      intravenous (i.v.) angiotensin II in the conscious rat, dog, and rhesus monkey. L
      163,017 also significantly reduces blood pressure in a renin-dependent model of
      hypertension, similar to an angiotensin converting enzyme inhibitor (Enalapril)
      and an angiotensin AT1 receptor-selective antagonist (L-159,282). These studies
      indicate that neither the angiotensin AT2 receptor nor bradykinin is important in
      the acute antihypertensive activity of angiotensin converting enzyme inhibitors
      or angiotensin II receptor antagonists.

PMID- 8750705
TI  - Sodium fluoride attenuates the negative inotropic effects of muscarinic M2 and
      adenosine receptor agonists.
AB  - Sodium fluoride increased the force of contraction in isolated guinea-pig
      papillary muscles concentration dependently, starting at 3 mmol/1. Sodium
      fluoride inhibited phosphorylase phosphatase activity in homogenates from guinea
      pig hearts, starting at 1 mmol/1. The positive inotropic effect of 3 mmol/1
      sodium fluoride was not accompanied by an increase in cAMP content in guinea-pig
      papillary muscles. In papillary muscles, carbachol or (-)-N(6)
      phenylisopropyladenosine reduced the positive inotropic effect of isoprenaline
      (10 nmol/1) or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (60 mu
      mol/1). These negative inotropic effects of carbachol and (-)-N(6)
      phenylisopropyladenosine were attenuated by additional sodium fluoride (3
      mmol/l). It is concluded that sodium fluoride can impair the signal transduction
      of muscarinic M2 (carbachol) and adenosine receptor (-)-N(6)
      phenylisopropyladenosine) agonists. This effect of sodium fluoride could support
      the hypothesis that the cardiac effects of muscarinic M2 and adenosine receptor
      agonists involve, at least in part, the activation of phosphatases.

PMID- 8750706
TI  - Differences between haloperidol- and pimozide-induced withdrawal syndrome: a role
      for Ca2+ channels.
AB  - We investigated the behavioral and biochemical events appearing in rats after
      withdrawal for 24 h or 8-12 days from two classical neuroleptics, haloperidol and
      pimozide. The neuroleptics were given for 14 days alone or shortly after
      injection of the Ca2+ channel blocker nifedipine. We have found that withdrawal
      effects after haloperidol and pimozide were different. After haloperidol
      treatment we observed an increase in cortical Ca2+ channel and limbic dopamine D1
      receptor density and an increase in spontaneous motor activity and apomorphine
      induced hyperactivity and stereotypy. In contrast no biochemical changes were
      observed during pimozide withdrawal, and locomotor activity and responses to
      apomorphine were depressed. Co-administration of nifedipine with haloperidol
      prevented the observed biochemical and behavioral symptoms of withdrawal.
      Nifedipine administration did not change the depressant effects of pimozide. Our
      results suggest that the voltage-dependent Ca2+ channel is involved in the
      observed withdrawal syndrome of neuroleptics, and that the absence of this
      syndrome after pimozide may be related to its considerable Ca2+ channel-blocking
      properties.

PMID- 8750707
TI  - Flupirtine protects neurons against excitotoxic or ischemic damage and inhibits
      the increase in cytosolic Ca2+ concentration.
AB  - We tested the effect of flupirtine against ischemic and excitotoxic neuronal
      damage as well as on the glutamate-induced rise in cytosolic calcium ion
      concentration (= [Ca2+]i). For in vivo experiments we used a model of focal
      cerebral ischemia in mice. The middle cerebral artery was permanently occluded
      and 48 h afterwards brain tissue was stained with neutral red, perfusion-fixed
      and the infarct surface was determined planimetrically. Pretreatment with
      flupirtine significantly reduced the infarct area (controls: 24.3 +/- 4.8 mm2, 1
      mg/kg flupirtine: 20.1 +/- 3.6 mm2 and 10 mg/kg flupirtine: 19.5 +/- 3.9 mm2; P <
      0.05), whereas postischemic application of flupirtine failed to reduce the
      infarct area. For in vitro studies, primary neuronal cultures were prepared from
      the hippocampi of newborn rats and excitotoxic damage was induced by exposing the
      cells to 500 mu M L-glutamate for 30 min. We could demonstrate that flupirtine (1
      10 microM) was capable of protecting neurons against glutamate-induced
      cytotoxicity. In order to elucidate the underlying mechanism of action, we tested
      the effect of flupirtine on the glutamate-induced rise in [Ca2+]i using the Ca2+
      indicator fura-2. L-Glutamate added in a final concentration of 100 microM to the
      cultured cells for 16 s caused a rise in [Ca2+]i from about 100 nM to 900 nM.
      Flupirtine (0.1-10 microM) reduced the glutamate-induced rise in [Ca2+]i
      concentration dependently.

PMID- 8750708
TI  - Felbamate neuroprotection against CA1 traumatic neuronal injury.
AB  - Traumatic brain injury is a leading cause of disability and death. Since the
      anticonvulsant felbamate provides hypoxic neuroprotection, we investigated
      whether felbamate would provide protection against traumatic neuronal injury as
      well. Traumatic injury to CA1 neurons in hippocampal slices was induced by fluid
      percussion, and CA1 evoked response was monitored. Pre-treatment with felbamate
      was strongly protective against neuronal injury, and permitted CA1 antidromic
      population spike recovery to a mean 94 +/- 1% (S.E.M.) of initial amplitude,
      compared to unmedicated slices which regained only 15 +/- 6%. The felbamate EC50
      for this protection was 136 mg/1, and significant protection was found at
      felbamate concentrations similar to those reported in felbamate monotherapy for
      seizures. Significant protection was also detected when felbamate was initiated
      15 min after trauma. Slices given brief post-trauma felbamate treatment could
      demonstrate long-term potentiation when assessed 8 h after trauma. These studies
      indicate that felbamate is neuroprotective against CA1 traumatic neuronal injury.

PMID- 8750709
TI  - Endothelin-1-induced in vitro cerebral venoconstriction is mediated by endothelin
      ETA receptors.
AB  - The in vitro effects of endothelin-1 on cerebral veins were studied using
      cylindrical segments, 5 mm long, from dog pial veins. Isometric responses to
      endothelin-1 (10(-12)-10(-7) M) and to the endothelin ET(B) receptor agonist, IRL
      1620 (Suc-[Glu9,Ala11,15]endothelin-1-(8-21), 10(-12) -10(-7) M), were recorded
      in veins under control conditions and pretreated with the endothelin ET(A)
      receptor antagonist, BQ-123 (cyclo-(D-Asp-Pro-D-Val-Leu-D-Trp), 10(-8) -10(-5)
      M), and the endothelin ETB receptor antagonist, BQ-788 (N-[N-[N-[(2,6-dimethyl-1
      piperidinyl)carbonyl]-4-methyl-L-leucyl]-1-(me thoxycarbonyl)-D-tryptophyl]-D
      norleucine monosodium, 10(-6) and 10(-5) M). The response to endothelin-1 was
      also recorded in veins pretreated with the nitric oxide synthesis inhibitor, N(G)
      nitro-L-arginine methyl ester (L-NAME, 10(-4) M), or the cyclooxygenase
      inhibitor, meclofenamate (10(-5) M), and in veins without endothelium or placed
      in medium without Ca2+ but with EDTA (0.1 mM). In control veins, endothelin-1
      produced a concentration-dependent contraction (EC50 = 2.0 x 10(-10) M; maximal
      contraction = 113 +/- 6 mg) and IRL 1620 induced no effects or a small
      contraction only with high concentrations (10(-8) - 10(-6) M) (EC50 = 1.5 x 10 (
      8) M; maximal contraction = 9 +/- 3 mg). BQ-123 shifted the response to
      endothelin-1 to the right in a parallel, concentration-dependent way, whereas BQ
      788, L-NAME or meclofenamate did not modify the response to endothelin-1.
      Compared with the control, veins in a medium without Ca2+ had similar EC50
      values, but a lower maximal contraction induced by endothelin-1 (57 +/- 10 mg, P
      < 0.05), and veins without endothelium exhibited similar EC50 values. Thus,
      endothelin-1 produces marked cerebral venoconstriction that could be mainly
      mediated by activation of endothelin ETA receptors, may be dependent on
      extracellular Ca2+, and may be independent of endothelium, nitric oxide and
      prostanoids.

PMID- 8750710
TI  - Effects of prostaglandin E2 on the intensity of bradykinin-evoked pain from skin
      and veins of humans.
AB  - Prostaglandin E2 increases bradykinin-induced spike activity from polymodal
      nociceptors of the skin and deep tissues in animals, suggesting sensitization of
      these receptors. To see whether these neurophysiological observations in animals
      correspond with increased pain intensity in humans, and whether also vascular
      nociceptors are sensitized, we studied in humans the effects of prostaglandin E2
      on the intensity of pain evoked by bradykinin via the nociceptive systems of skin
      and veins. In seven healthy subjects, bradykinin was injected into the skin and
      into a vascularly isolated hand vein segment, prior to and after local
      application of prostaglandin E2. Subsequent pain intensity was recorded
      continuously with an electronically controlled visual analogue scale.
      Prostaglandin E2 alone never elicited pain, but without exception increased the
      intensity of bradykinin-induced pain in a concentration-related manner at
      concentrations from 10(-9) to 10(-6) M, both in skin and veins. Thus, bradykinin
      is more painful after pretreatment with prostaglandin E2, suggesting
      sensitization of nociceptors of the skin, but also of hand veins in humans.

PMID- 8750711
TI  - 1S,3R-ACPD dose dependently induces a slow onset potentiation in the dentate
      gyrus in vivo.
AB  - It has been demonstrated by others in vitro that application of 1S,3R
      aminocyclopentane-2,3-dicarboxylic acid (ACPD) facilitates long-term potentiation
      and triggers a slow-onset potentiation in the hippocampus. This study examined
      the effect of ACPD in the dentate gyrus when applied in vivo. Weak tetanisation
      produced a short-term potentiation of field excitatory post-synaptic potential
      (EPSP) and population spike. A similar response was seen upon application of ACPD
      (40 microM in 5 microl vehicle) via the lateral cerebral ventricle 30 min prior
      to tetanus, whereas ACPD (80 microM/5 microl) facilitated short-term potentiation
      into long-term potentiation. (R,S)-alpha-Methyl-4-carboxyphenyl-glycine (MCPG 200
      mM/5 microl), completely inhibited this effect. ACPD had no effect on baseline
      recordings at 40 and 80 microM/5 miccrol, however 4 mM/5 microl ACPD induced a
      slow-onset potentiation of field EPSP and population spike which was maintained
      for over 4 h. MCPG or D-2-amino-5-phosphonopentanoate (AP5 20 mM/5 microl)
      applied prior to ACPD completely inhibited this effect. These results suggest
      that previously reported in vitro effects of ACPD in the CA1 region, also occur
      in the dentate gyrus in vivo. Furthermore, they confirm that activation of mGlu
      receptors by ACPD in vivo facilitates long-term potentiation, and indicate that
      in the dentate gyrus, ACPD-induced slow-onset potentiation is NMDA receptor
      dependent.

PMID- 8750712
TI  - Nitric oxide is involved in male sexual behavior of rats.
AB  - In male rats, whether sexually experienced or sexually naive, the intraperitoneal
      administration of L-arginine (the natural substrate for nitric oxide synthase)
      (10, 25, 50 mg/kg) both increased the percentage of copulating in sexually naive
      rats and improved the indexes of sexual performance in sexually experienced rats,
      whereas the intraperitoneal administration of N(G)-nitro-L-arginine methyl ester
      (L-NAME) (a potent inhibitor of nitric oxide synthase) (10, 25, 50 mg/kg) had
      opposite effects. In contrast, after intracerebroventricular administration, L
      arginine (25, 50, 100 microg/rat) had no effect - whether in naive or in
      experienced rats - whereas L-NAME completely prevented ejaculation in naive rats,
      at the dose of 100 microg/rat, but had no effect at all in experienced rats, up
      to the dose of 300 microg/rat. Finally, a direct relationship seems to exist
      between male copulatory performance and nitric oxide synthase activity in a
      discrete and defined brain area, the paraventricular nucleus of the hypothalamus:
      indeed, nitric oxide synthase mRNA expression in this nucleus in sexually potent
      rats is about twice that in sexually impotent rats. It is concluded that nitric
      oxide synthase is involved in the expression of male sexual activity, in spite of
      some inconsistencies that are hard to interpret.

PMID- 8750713
TI  - Are C-terminal octapeptide of cholecystokinin and [Leu11]gastrin-(5-17) different
      in stimulating acid secretion in isolated rabbit gastric glands?
AB  - In the present study we compared various CCK(B) receptor antagonists and tried to
      detect a difference in biological activity between the C-terminal octapeptides of
      cholecystokinin (CCK-8) and [Leu11]gastrin-(5-17) in isolated rabbit gastric
      glands. Binding experiments showed that different CCK(B)/gastrin receptor
      agonists bound with high affinity and that antagonists inhibited this binding in
      accordance with a CCK(B)/gastrin pharmacological profile. [Leu11]gastrin-(5-17),
      CCK-8 and cionin were found to induce [14C]aminopyrine accumulation to 25% above
      the basal level. Under the same experimental conditions, histamine induced a
      response twice as great as the response obtained with [Leu11]gastrin-(5-17) or
      CCK-8. [Leu11]gastrin-(5-17) (10(-7) M), CCK-8 (10(-8) M) and cionin (10(-8) M)
      appeared to be full agonists. CCK(B)/gastrin receptor antagonists including L
      365,260 (3R-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin++  +
      3-yl)-N-(3-methylphenyl) urea), L-364,718 (3S-(-)-N-(2,3-dihydro-1-methyl-2-oxo-5
      phenyl-1H-1,4-benzodiazepin++  +-3-yl)-1H-indole-2-carboximide) (a selective
      CCK(A) receptor antagonist), PD-135,158 (4([2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo
      2-[[[1.7.7-trimethyl-bicyclo[2. 2.1]hept-2-yl)oxy]carbonyl]amino]propyl]amino]-1
      phenylethyl] amino-4-oxo-[1S-1alpha.2beta[S*(S*)]4alpha]]-butano  nate N-methyl-D
      glucamine) (bicyclo system 1S-endo), YM-022 ((R)-1-[2,3-dihydro-1-(2'
      methylphenacyl)-2-oxo-5-phenyl-1H-1,4-++ +benzodiazepin-3-yl]-3-(3
      methylphenyl)urea) and JMV-180 (Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-O-CH2-CH2-C6H5)
      exhibited the same profile for inhibition of [Leu11]gastrin-(5-17) or CCK-8
      induced [14C]aminopyrine accumulation in rabbit gastric glands. These results
      suggested that [Leu11]gastrin-(5-17) and CCK-8 induced [14C]aminopyrine
      accumulation by the same mechanism. [Leu11]gastrin-(5-17)- or CCK-8-induced
      [14C]aminopyrine accumulation was inhibited by about 40% by the histamine H2
      receptor blocker cimetidine. These results are consistent with there being
      cooperativity between [Leu11]gastrin-(5-17) (or CCK-8) and histamine in the acid
      secretory pathway. Similarly, the CCK(B)/gastrin receptor antagonists were tested
      against histamine-induced [14C]aminopyrine accumulation and surprisingly, only
      compound L-365,260 appeared active and even more potent than cimetidine.

PMID- 8750714
TI  - Pharmacological dissociation of UTP- and ATP-elicited contractions and
      relaxations in isolated rat aorta.
AB  - Effects of UTP have been described in many tissues, but it is not clear whether
      these are due to purinoceptors. Specific receptors for UTP, 'pyrimidinoceptors',
      and 'nucleotide receptors' have also been proposed. We pharmacologically
      characterized the receptors involved in the ATP- and UTP-induced contraction
      under basal tone and the relaxation of raised tone elicited by noradrenaline in
      isolated rat aorta. The rank order of potency for the agonists for the
      contraction was alpha,beta-methylene ATP > > ATP, and the desensitization by
      alpha,beta-methylene ATP suggests that ATP contractions were mediated via P2X
      purinoceptors which were located on the vascular smooth muscle. The rank order of
      potency of the agonists for relaxation was 2-methyl-thio ATP > > ATP, which is
      suggestive of a P2Y purinoceptor. However, the relaxation seems to be unrelated
      to the classical P2Y subtype and a heterogeneous population of purinoceptors
      might therefore exist. The evidence comes from the distinct location and the
      different pharmacological effect of reactive blue 2 on 2-methyl-thio ATP and ATP
      receptors. 2-Methyl-thio ATP produced an endothelium-dependent relaxation while
      ATP-induced relaxation was produced via endothelium-dependent and endothelium
      independent mechanisms, unrelated to adenosine receptors. It is unlikely that UTP
      induced contractions and the endothelium-dependent relaxation were produced via
      purinoceptors since the pharmacology is not consistent with that of the classical
      P2 purinoceptors studied. Furthermore, UTP-sensitive receptors showed a
      pharmacological property that was also distinct from that of the 'nucleotide' or
      P2U receptor reported. The results suggest the presence of a heterogeneous
      population of purinoceptors and pyrimidinoceptors pharmacologically different
      from the receptors for ATP.

PMID- 8750716
TI  - Differential effects of phenytoin and sodium valproate on seizure-induced changes
      in gamma-aminobutyric acid and glutamate release in vivo.
AB  - The effects of intraperitoneal administration of the anticonvulsants phenytoin
      and sodium valproate were compared with ethosuximide on maximal electroshock
      seizure-related changes in rat hippocampal gamma-aminobutyric acid (GABA) and
      glutamate release in vivo as measured by microdialysis. There were immediate
      increases in GABA and glutamate in the 5 min post-ictal period, followed by a
      sustained reduction in GABA levels. Glutamate levels, however, were subsequently
      reduced until 20 min post-ictal before gradually increasing above basal. All
      animals displayed tonic hind-limb extension that was blocked by phenytoin (20
      mg/kg) and sodium valproate (400 mg/kg) but not ethosuximide (150 mg/kg).
      Phenytoin attenuated the immediate post-ictal increase observed in glutamate
      whilst sodium valproate enhanced GABA release and prevented its secondary post
      ictal inhibition. Ethosuximide was without effect on the post-ictal changes.
      These are the first data to show detailed seizure-induced amino acid changes and
      the in vivo effects of anticonvulsants on them in the seizure model.

PMID- 8750715
TI  - Effects of stress on the functional properties of pre- and postsynaptic 5-HT1B
      receptors in the rat brain.
AB  - Numerous studies have clearly shown that the turnover and release of serotonin (5
      hydroxytryptamine, 5-HT) are increased under acute stressful conditions. Inasmuch
      as this latter process is under the control of a feedback mechanism involving the
      stimulation of presynaptic 5-HT1B autoreceptors, we have investigated the
      possible effects of acute restraint (40 min) on the functional properties of 5
      HT1B receptors. The efficacy of the selective 5-HT1B receptor agonist 3-[1,2,5,6
      tetrahydropyrid-4-yl]pyrrolo-[3,2-b]pyrid-5-one (CP-93,129) in inhibiting in
      vitro the K+-evoked release of [3H]5-HT, was significantly reduced in stressed
      rats as compared to naive animals. Similarly, the responsiveness of 5-HT1B
      receptors inhibiting the release of [3H]acetylcholine (presynaptic 5-HT1B
      heteroreceptors), was reduced by restraint. These effects were observed in the
      hippocampus, but using the inhibitory effect of CP-93,129 on forskolin-stimulated
      adenylyl cyclase activity as an index of 5-HT1B receptor function, it could be
      shown that the 5-HT1B receptors located in the substantia nigra are also
      desensitized by stress. The number as well as the apparent affinity constant of 5
      HT1B binding sites labelled by [125I]iodocyanopindolol, as measured by
      quantitative autoradiography and membrane binding, were similar in naive and
      restraint-stressed rats suggesting that the stress-induced desensitization of 5
      HT1B receptors is not due to a reduced number of 5-HT1B binding sites. As stress
      is thought to be a causal factor for the etiology of anxiety and depression,
      these results support the potential involvement of 5-HT1B receptor dysfunction in
      the development of these neurological disorders.

PMID- 8750717
TI  - sigma2 Site-mediated inhibition of electrically evoked guinea pig ileum
      longitudinal muscle/myenteric plexus contractions.
AB  - Functional and binding studies were performed in order to characterize the
      relative efficacy and affinity of a number of compounds that bind to sigma sites.
      The ability of sigma site ligands to inhibit electrically evoked contraction of
      the guinea pig ileum longitudinal muscle/myenteric plexus preparation was
      compared to the affinities of these compounds for sigma1 sites (assessed by
      displacement of [3H](+)-pentazocine) and sigma2 sites (assessed by displacement
      of [3H]1,3-di-o-tolylguanidine (DTG) in the presence of 5 microM
      dextromethorphan). It was shown that the rank order of potencies for suppression
      of electrically evoked contractions of guinea pig ileum perfectly matched the
      rank order of affinities of these compounds for the sigma2 binding site, while
      correlating poorly with the sigma1 binding site. In addition, no significant
      correlations were found between the efficacy of the tested compounds to inhibit
      contraction of the guinea pig ileum preparation and previously reported
      affinities for muscarinic, dopamine D2 or MK-801 binding sites. Thus, the present
      study represents the first functional bioassay selectively sensitive to agents
      interacting with the sigma2 receptor subtype binding site, and provides a means
      with which to further elucidate the functional role of sigma2 sites.

PMID- 8750718
TI  - Effect of a new de-N-acetyl-lysoglycosphingolipid on some tumour models.
AB  - A new de-N-acetylated glycosphingolipid termed WILD20, a breakdown product of GM1
      obtained through alkaline hydrolysis, and characterized by nuclear magnetic
      resonance, mass spectrometry and elementary analysis, was found to inhibit
      phospholipase A2 via phosphokinase C translocation blockade. The substance
      inhibited various tumour cell lines in vitro, in synergy with doxorubicin and
      cisplatin. In vivo, it showed an antitumoral effect when both the tumour cells
      and WILD20 were injected at the same site (peritoneal cavity). Tumour cells,
      incubated with WILD20, showed a dose-dependent decrease of oncogenicity without
      impairment of viability. WILD20 also down-regulated tumour cell adherence to
      laminin and fibronectin. When peritumorally administered, WILD20 impaired tumour
      growth and potentiated the peritumoral effects of recombinant interleukin 2. The
      results obtained merit exploration of the therapeutical possibilities of this
      agent in human cancer patients.

PMID- 8750719
TI  - Changes in the regulation of 5-hydroxytryptamine release by alpha2-adrenoceptors
      in the rat hippocampus after long-term desipramine treatment.
AB  - In vivo microdialysis was used to measure the effects of long-term treatment of
      rats with desipramine upon the regulation by alpha2-adrenoceptors of serotonin (5
      hydroxytryptamine, 5-HT) release from the serotonergic neurons in the
      hippocampus. Rats were injected with saline or desipramine, 10 mg/kg, i.p., every
      12 h for 14 days. When added to the perfusion solution, brimonidine, an alpha2
      adrenoceptor agonist, significantly inhibited the K+-evoked release of 5-HT in
      the hippocampi of saline-treated, control rats. This action of brimonidine was
      prevented by pretreating the rats with idazoxan, an alpha2-adrenoceptor
      antagonist. Long-term desipramine treatment significantly reduced the inhibitory
      effect of brimonidine upon the K+-evoked 5-HT release. With long-term
      administration of desipramine, noradrenaline content in the hippocampi was
      significantly decreased as compared with that of the control rats, whereas the
      basal noradrenaline concentration in the dialysate was significantly increased.
      On the other hand, both the 5-HT content of the hippocampus and the basal 5-HT
      concentration in the dialysate were significantly increased. The present study
      suggests that long-term administration of desipramine causes a functional
      subsensitivity of the presynaptic alpha2-adrenoceptors that regulate serotonergic
      neuronal function in the rat hippocampus. It also supports the concept that
      changes in the sensitivity of alpha2-adrenoceptors that regulate neurotransmitter
      release play an important role in the mechanism of antidepressant drug action.

PMID- 8750720
TI  - Prevention of cyclosporine A-induced renal vasoconstriction by the endothelin
      receptor antagonist SB 209670.
AB  - Administration of endothelin to inactin-anesthetized rats resulted in a
      significant renal vasoconstriction as evidenced by a reduction in both renal
      plasma flow and glomerular filtration rate. Infusion of the novel nonpeptide
      endothelin ETA/ETB receptor antagonist, (+/-)-SB 209670, [(1RS-2SR,3RS)-3-(2
      carboxymethoxy-4-methoxy-phenyl)-5 -(prop-1-yloxy)indane-2-carboxylic acid],
      significantly attenuated the renal vascular effects of endothelin-1. Intravenous
      administration of cyclosporine A (50 mg/kg) caused a significant reduction in
      renal plasma flow and glomerular filtration rate and urine flow and a dramatic
      increase in renal vascular resistance. Concomitant infusion of (+/-)-SB 209670
      abolished the cyclosporine A-induced reduction in renal plasma flow and
      glomerular filtration rate and attenuated the cyclosporine A-induced fluid
      retention. The data indicate that endothelin is involved in the acute renal
      effects of cyclosporine A.

PMID- 8750721
TI  - The vesicular monoamine transporter is not regulated by dopaminergic drug
      treatments.
AB  - The number of neuronal synaptic vesicular monoamine transporters (vesicular
      monoamine transporter type 2; VMAT2) has been recently proposed as an index of
      monoamine presynaptic terminal density. The present study investigated the
      possible regulation of the vesicular monoamine transporter. Rats were treated for
      2 weeks with drugs known to influence dopaminergic neurotransmission, including
      those commonly used in the treatment of Parkinson's disease. Autoradiographic
      assays were performed using [3H]methoxytetrabenazine, [3H]raclopride, and [3H]WIN
      35,428 ([3H]2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane) to measure
      vesicular monoamine transporter, dopamine D2 receptor and synaptic plasma
      membrane dopamine re-uptake site bindings, respectively. None of the drug
      treatments significantly modified levels of vesicular monoamine transporter
      binding. In contrast, both dopamine D2 receptors and dopamine re-uptake sites
      were altered by some of the treatment regimens. These data extend preliminary
      results that suggest the vesicular monoamine transporter is not easily regulated
      and confirm the plasticity of dopamine D2 receptors and the dopamine re-uptake
      site. Measures of striatal vesicular monoamine transporter density may, thus,
      provide objective estimates of monoaminergic innervation in neurodegenerative
      diseases, unaffected by the use of symptomatic therapies.

PMID- 8750722
TI  - Carvedilol prevents low-density lipoprotein (LDL)-enhanced monocyte adhesion to
      endothelial cells by inhibition of LDL oxidation.
AB  - Cultured human umbilical vein endothelial cells oxidize low-density lipoproteins
      (LDL), assessed as increase in thiobarbituric acid reactive substance formation
      and oxidized LDL-induced cytotoxicity (lactate dehydrogenase (LDH) release).
      Endothelial cell-generated oxidized also enhances the adhesiveness of endothelial
      cells to monocytes. Carvedilol, a new vasodilating beta-adrenoceptor antagonist,
      inhibits the oxidation of LDL by endothelial cells and reduces oxidized LDL
      induced LDH release from endothelial cells in a concentration-dependent manner
      with IC50 values of 2.56 and 1.38 microM, respectively. Moreover, carvedilol
      inhibits oxidized LDL-induced adhesion of monocytes to the endothelial cells in a
      similar concentration-dependent manner. Under the same conditions, propranolol,
      atenolol, pindolol and labetalol had only weak or no consistent effects on both
      LDL oxidation by endothelial cells and adhesion of monocytes to the endothelial
      cells. Monoclonal antibodies against human intercellular adhesion molecule-1
      (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) or E-selectin (ELAM-1)
      partially blocked oxidized LDL-stimulated adhesion of endothelial cells to
      monocytes. The inhibitory effects of carvedilol on LDL oxidation and monocyte
      adhesion to endothelial cells may protect blood vessels from atherosclerotic
      processes associated with oxidized LDL-induced injuries.

PMID- 8750723
TI  - Alterations of alpha1-adrenoceptor subtypes in the hearts of thyroxine-treated
      rats.
AB  - Alterations in the cardiac alpha1-adrenoceptor and its subtypes in thyroxine
      treated rats were studied by means of radioligand binding assays, measurement of
      contractile response and reverse transcription-polymerase chain reaction (RT
      PCR). The results showed that in thyroxine-treated rats the cardiac alpha1
      adrenoceptor density (Bmax) was reduced from 51.6 +/- 6.0 fmol/mg in control to
      40.9 +/- 3.7 fmol/mg (P<0.01); and the percentage of high affinity sites for 5
      methyl-urapidil decreased from 23.3 +/- 2.0% in control to 10.8 +/- 2.0% in
      thyroxine-treated rats (P<0.05). The data indicated that the high-affinity sites
      for 5-methyl-urapidil (alpha1A-adrenoceptor) were reduced (from 12.0 to 4.4
      fmol/mg), but the low-affinity sites for 5-methyl-urapidil (alpha1B- plus alpha1D
      adrenoceptor) were not changed (from 39.6 to 36.5 fmol/mg). RT-PCR showed that
      steady-state levels of mRNA for alpha1A- and alpha1B-adrenoceptors were
      decreased, while that for alpha1D-adrenoceptor was raised in thyroxine-treated
      rats. In the isolated electrically driven left atria the phenylephrine-induced
      maximal contractions were reduced from 258 +/- 17 mg in control to 188 +/- 24 mg
      in thyroxine-treated rats (P<0.05). The pA2 values of 5-methyl-urapidil were
      reduced from 8.89 +/- 0.36 in control to the hyperthyroidism of 7.87 +/- 0.43 in
      thyroxine-treated rats (P<0.05). Chlorethylclonidine preincubation shifted
      concentration-response curves for phenylephrine to the right and reduced the
      maximal response to a lesser extent in thyroxine-treated rats than in control
      rats. Thus we concluded that the total number of cardiac alpha1-adrenoceptors is
      reduced in thyroxine-treated rats. The change is subtype selective, with alpha1A-
      and alpha1B-adrenoceptors being reduced in number and alpha1D-adrenoceptor being
      increased.

PMID- 8750724
TI  - Peripheral benzodiazepine receptor ligands in rat liver mitochondria: effect on
      cholesterol translocation.
AB  - Peripheral benzodiazepine receptors mediate cholesterol translocation between the
      outer and inner mitochondrial membranes in steroidogenic tissues. They are found
      in many other tissues too, including liver. We studied the effect of the
      peripheral benzodiazepine receptor ligands PK11195 [1-(2-chlorophenyl)-N-methyl-N
      (1-methylpropyl)isoquinoline-3-carboxa  mid e], Ro 5-4864 (4-chlorodiazepam),
      hemin, protoporphyrin IX and N-methyl protoporphyrin IX on cholesterol
      mitochondrial intermembrane transport of cholesterol in vitro in rat liver.
      Endogenous cholesterol translocation from outer to inner mitochondrial membranes
      was significantly increased by PK11195 and N-methyl protoporphyrin IX (140% and
      150% increase, respectively, at 1 microM, P<0.01). 5 microM protoporphyrin IX, 1
      microM Ro 5-4864 and 5 microM hemin was ineffective. When mitochondria were
      labeled with exogenous [4-14C]cholesterol, PK11195 and N-methyl protoporphyrin IX
      were the most effective in increasing total cholesterol incorporation and
      cholesterol translocation into inner membranes, and their effect was dose
      dependent. These data suggest that in liver the binding to peripheral
      benzodiazepine receptors is related to cholesterol translocation and the
      interaction of ligands with these receptors may play a role in the complex
      mechanism of regulation of cholesterol traffic between liver mitochondrial
      membranes.

PMID- 8750725
TI  - Antinociceptive effect of alpha-trinositol, a novel D-myo-inositol phosphate
      derivative, in the formalin test in rats.
AB  - The antinociceptive effect of alpha-trinositol was examined in rats using the
      formalin test following systemic, spinal and local subcutaneous administration.
      Injection of formalin into the paw evoked two phases (phase 1: 0-9 min; phase 2:
      10-60 min) of flinching behavior of the injected paw. Intrathecal administration
      of alpha-trinositol resulted in a dose-dependent suppression of the first (ED50:
      8 microg) and second (ED50: 9 microg) phase of formalin-evoked behavioral
      response. Similarly, intraperitoneal delivery showed a dose-dependent reduction
      of the first (ED50: 83 mg/kg) and second (ED50: 56 mg/kg) phase of the formalin
      test. Subcutaneous injection of 100 microg, but not 10 mu g, alpha-trinositol
      into the rat paw together with the formalin solution, had no effect on the first
      phase, but reduced by 20% the second phase of behavior. These data show that
      alpha-trinositol produces a suppression of acute and prolonged nociceptive
      behaviors with a central mechanism of action, although some peripheral component
      may contribute to the reduction of the late phase following systemic
      administration.

PMID- 8750726
TI  - The azapirone metabolite 1-(2-pyrimidinyl)piperazine depresses excitatory
      synaptic transmission in the hippocampus of the alert rat via 5-HT1A receptors.
AB  - The effects of acute and repeated treatment with 1-(2-pyrimidinyl)piperazine (1
      PP), a metabolite of the 5-HT1A receptor ligand azapirones, were investigated on
      hippocampal excitatory synaptic transmission. Recordings of the electrically
      evoked field population excitatory post-synaptic potentials (e.p.s.p.s.) were
      carried out in the stratum radiatum of the CA1 region of the dorsal hippocampus
      of alert rats. Acute i.p. administration of 1-PP transiently reduced the e.p.s.p.
      amplitude in a dose-dependent (0.25-1 mg/kg) manner. This effect was blocked by
      the 5-HT1A receptor antagonists spiroxatrine (1 mg/kg) and MDL 73005EF (8-[2-(2,3
      dihydro-1,4-benzodioxin-2-yl methylaminoethyl]-8-azaspirol[4,5]decane-7,9-dione
      methyl sulphonate, 2 mg/kg). Intrahippocampal administration of 1-PP (5 microg)
      evoked a transient reduction of the e.p.s.p. amplitude which was similar to that
      obtained with 5-HT (10 microg). 1-PP (0.25 mg/kg per day) administered for 9 days
      produced a gradual reduction in the daily pre-injection baseline e.p.s.p.
      amplitude coupled with a decrease in the acute response to the drug. The chronic
      baseline reduction was transiently reversed by spiroxatrine and full recovery to
      pretreatment levels was observed 4 days after the last 1-PP dose. These findings
      indicate that the previously reported reduction in the e.p.s.p. produced by the
      azapirone group of 5-HT1A receptor ligands may be mediated in part by their
      metabolite 1-PP through activation of 5-HT1A receptors.

PMID- 8750727
TI  - 17beta-Estradiol inhibits the voltage-dependent L-type Ca2+ currents in aortic
      smooth muscle cells.
AB  - To elucidate the mechanisms of estrogens-induced relaxation effects on vascular
      smooth muscle cells, the effects of estrogens and the related hormones were
      examined in cultured rat thoracic aortic smooth muscle cell lines (A7r5), using
      the whole-cell voltage clamp technique. The patch pipette was filled with 140 mM
      CsCl- or KCl-containing internal solution. With CsCl-internal solution, 17beta
      estradiol and synthetic estrogens, ethynylestradiol and diethylstilbestrol (0.1
      30 mu M) inhibited the Ba2+ inward current (IBa) through the voltage-dependent L
      type Ca2+ channel in a concentration-dependent and reversible manner. The potency
      of the inhibitory effects on IBa was 17beta-estradiol < ethynylestradiol <
      diethylstilbestrol. 17beta-Estradiol (10 mu M) appeared to reduce the maximal
      conductance of IBa with only a slight shift of voltage-dependency of inactivation
      and to affect IBa in a use-independent fashion. On the other hand, testosterone
      and progesterone (30 mu M) failed to affect IBa. At a holding potential of -40
      mV, both vasopressin and endothelin-1 (100 nM) activated a long-lasting inward
      current. After endothelin-1 (100 nM) activated the current, the additional
      application of vasopressin (100 nM) could not induce it furthermore, suggesting
      that each agonist activates the same population of the channels. The reversal
      potential of the current was about 0 mV and was not significantly altered by
      replacement of [Cl-]i or [Cl-]0 and the inward current was also observed even
      when extracellular cations are Ca2+, proposing that it was a Ca2+-permeable non
      selective cation channel (IN.S.). La3+ or Cd2+ (1 nM) completely abolished IN.S.,
      however, nifedipine (10 mu M) failed to inhibit it at all. Diethylstilbestrol (1
      30 mu M) suppressed the IN.S. evoked by both endothelin-1 and vasopressin in a
      concentration-dependent manner, while 17beta-estradiol, ethynylestradiol,
      progesterone and testosterone (30 mu M) failed to inhibit it significantly. In
      addition, at a holding potential of +0 mV, 17beta-estradiol by itself did not
      affect the holding currents, and did not inhibit K+ currents evoked by endothelin
      1 or vasopressin, possibly due to the Ca2+ release from the storage sites. These
      results suggest that 17beta-estradiol may play a role in regulating vascular
      tone, selectively by inhibiting the voltage-dependent L-type Ca2+ current in
      vascular smooth muscle cells.

PMID- 8750728
TI  - Intrastriatal injection of opioid receptor agonists inhibits apomorphine-induced
      behavior in 6-hydroxydopamine-treated mice.
AB  - The effects of intrastriatal (i.st.) injections of mu-, delta-, and kappa
      selective opioid receptor agonists on the augmentation of apomorphine-induced
      behaviors were determined in 6-hydroxydopamine-treated mice by using
      multidimensional behavioral analyses. 6-Hydroxydopamine (16 mu g/mu l, i.st.) was
      unilaterally injected into the striatum 30 min after pretreatment with
      desipramine (25 mg/kg, s.c). Mice were tested 14 days after injection of 6
      hydroxydopamine. Apomorphine (0.5 mg/kg, s.c.) produced a marked increase in
      linear locomotion, contralateral circling and/or rearing behavior in 6
      hydroxydopamine- but not vehicle-treated mice. Although the mu-selective opioid
      receptor agonist [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) (0.1 and 0.3 ng,
      i.st.) or the kappa-selective opioid agonist dynorphin A-(1-13) (0.1 and 0.3 mu
      g, i.st.) did not produce any significant effects on behavior, these peptides had
      an inhibitory effect on the apomorphine (0.5 mg/kg, s.c.)-induced increase in
      behavioral responses such as linear locomotion, contralateral circling and/or
      rearing behavior in 6-hydroxydopamine-treated mice. The inhibitory effects of
      DAMGO (0.3 ng, i.st.) and dynorphin A-(1-13) (0.3 mu g, i.st.) were fully
      reversed by selective opioid receptor antagonists such as beta-funaltrexamine (5
      mu g, i.c.v.) and (--)-(1R,5R,9R)-5,9-diethyl-2-(3-furyl-methyl)-2'-hydroxy-6,7
      benzomorph an (Mr2266) (10 mg/kg, s.c.), respectively. In contrast, the delta
      selective opioid receptor agonist [D-Pen2,L-Pen5]enkephalin (DPLPE) (0.03, 0.1 or
      0.3 mu g, i.st.) had no marked effects on the apomorphine (0.5 mg/kg, s.c.)
      induced behavior in 6-hydroxydopamine-treated mice. These results suggest that
      the stimulation of mu- and kappa- but not delta-opioid receptors plays an
      inhibitory role in the behavioral augmentation induced by the activation of
      postsynaptic dopamine receptors in the striatum sensitized with 6
      hydroxydopamine.

PMID- 8750729
TI  - A comparison of the effects of doxazosin and terazosin on the spontaneous
      sympathetic drive to the bladder and related organs in anaesthetized cats.
AB  - The effects of i.v. infusion of the alpha1-adrenoceptor antagonists doxazosin and
      terazosin (2 mg kg-1 h-1) on spontaneous hypogastric, renal and inferior cardiac
      nerve activity, spontaneous bladder contractions, blood pressure, heart rate and
      femoral arterial flow were investigated separately in alpha-chloralose
      anaesthetized cats. Both drugs caused a reduction in hypogastric nerve activity
      associated with no overt changes in spontaneous bladder contractions. Doxazosin
      was more potent than terazosin, in that there was a significant reduction in
      hypogastric nerve activity after 20 min (0.67 mg kg-1) of infusion, while for
      terazosin this occurred after 40 min (1.33 mg kg-1). Both drugs also caused
      significant falls in blood pressure of 34 +/- 3 mm Hg and 33 +/- 4 mm Hg after 60
      min. This was associated with no change in heart rate for doxazosin while
      terazosin caused an initial and significant increase in heart rate of 20 +/- 3
      beats min-1 by 5 min, declining by 30 min to 1 +/- 5 beats min-1. This terazosin
      induced tachycardia was associated with a significant increase in cardiac nerve
      activity of 128 +/- 22%. Both drugs caused increases in renal nerve activity
      however only for doxazosin was this increase significant. Femoral arterial
      conductance was also increased by both drugs, however, for doxazosin this
      increase was immediate and larger over the infusion period. These results
      demonstrate that alpha1-adrenoceptor antagonists can reduce sympathetic drive to
      the bladder and related organs.

PMID- 8750730
TI  - Buprenorphine blocks diffuse noxious inhibitory controls in the rat.
AB  - A C-fibre reflex elicited by electrical stimulation within the territory of the
      sural nerve was recorded from the ipsilateral biceps femoris muscle in
      anaesthetised rats. Such reflex responses can be inhibited by applying noxious
      conditioning stimuli to heterotopic areas of the body. These inhibitory processes
      have been termed diffuse noxious inhibitory controls. The responses were recorded
      before, during and after the immersion of the tail in a thermoregulated waterbath
      (at 50 degrees C) for 1 min. The C-fibre reflex responses were depressed by a
      maximum of 71 +/- 3% at 45 s after the start of such conditioning stimuli. A dose
      of 3 mu g/kg buprenorphine completely blocked the inhibition and post-stimulus
      effects triggered by the heterotopic noxious stimuli. In the 0.3-3 mu g/kg range,
      buprenorphine increased, in a dose-dependent manner, the magnitude of the
      inhibition. These doses did not produce any changes in the C-fibre reflex itself.
      The results are discussed in terms of the mechanisms underlying the analgesic
      properties of buprenorphine.

PMID- 8750731
TI  - Neuropeptide Y accounts for sympathetic vasoconstriction in guinea-pig vena cava:
      evidence using BIBP 3226 and 3435.
AB  - The ability of the novel, non-peptide, neuropeptide Y Y1 receptor antagonist,
      BIBP 3226 ((R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-argininami de), to
      antagonize neuropeptide Y- and sympathetic-mediated vasoconstriction was examined
      in isolated segments of the thoracic vena cava of guinea-pigs. Increasing
      concentrations (10(-9) - 10(-6) M) of BIBP 3226 caused a parallel and rightward
      shift in the neuropeptide Y dose-response curve but did not significantly change
      the effect of noradrenaline. The calculated pA2 value for BIBP 3226 was 8.0 +/-
      0.08, a value fully compatible with the reported affinity at rodent and human
      neuronal Y1 receptors. BIBP 3226 (10(-6) M) also readily reversed the established
      vasocontraction induced by neuropeptide Y. BIBP 3226 (10(-6) M) markedly
      inhibited the slow long-lasting contraction evoked by high frequency electrical
      field stimulation, leaving a rapid component which was abolished by phentolamine.
      Its enantiomer, BIBP 3435 ((S)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]
      argininami de), which exerts a much weaker action on neuropeptide Y Y1 receptors,
      had no such inhibitory effect. In propranolol-pretreated vessels, the
      vasoconstriction evoked by nerve stimulation was enhanced; then BIBP 3226
      inhibited the peak response by 44%, and the integrated contractile effect by 90%.
      We conclude that BIBP 3226 is a potent and competitive antagonist of neuropeptide
      Y Y1 receptor-mediated vasoconstriction in guinea-pig vena cava and that
      endogenous neuropeptide Y acting on the neuropeptide Y Y1 receptor is likely to
      account for the long-lasting component of the sympathetic vasoconstriction in
      response to high-frequency stimulation in this vessel.

PMID- 8750732
TI  - Fenspiride: an anti-inflammatory drug with potential benefits in the treatment of
      endotoxemia.
AB  - Using a model of endotoxemia triggered by the intravenous injection of bacterial
      lipopolysaccharide (0.1 and 1 mg/kg) to guinea-pigs, we investigated the
      interference of fenspiride, an anti-inflammatory drug recommended for the
      treatment of inflammatory diseases of the upper respiratory tract. Administered
      orally at 60 mg/kg, fenspiride reduced the lipopolysaccharide-induced early rise
      of tumor necrosis factor concentrations in serum (4.2 +/- 0.9 vs. 2.3 +/- 0.5
      ng/ml, P < 0.05) and in the bronchoalveolar lavage fluid (55.7 +/- 20 vs. 19.7 +/
      7.5 ng/ml, P < 0.05). The lipopolysaccharide-induced primed stimulation of
      alveolar macrophages, defined as their enhanced release of arachidonic acid
      metabolites as compared to cells from untreated controls upon stimulation with N
      formyl-methionyl-phenylalanine was also reduced by fenspiride (1551.5 +/- 183.7
      vs. 771.5 +/- 237.5 pg/mu g protein, P < 0.05 for thromboxane B2 and 12.6 +/- 4.9
      vs. 3.6 +/- 0.9 pg/ mu g protein, P < 0.05 for leukotriene C4). Finally,
      fenspiride reduced the increased serum concentrations of extracellular type II
      phospholipase A2 (3.9 +/- 1.2 vs. 1.2 +/- 0.1 nmol/ml per min, P < 0.01), the
      intensity of the neutrophilic alveolar invasion and the lethality due to the
      lipopolysaccharide. The protective effect of fenspiride may result from the
      inhibition of the formation of tumor necrosis factor, a major mediator of the
      effects of lipopolysaccharide.

PMID- 8750733
TI  - In vitro and in vivo pharmacology of S 16474, a novel dual tachykinin NK1 and NK2
      receptor antagonist.
AB  - Since tachykinins released from lung sensory nerve endings are thought to play a
      role in inflammatory diseases of airways via NK1 and NK2 receptors, dual
      tachykinin NK1 and NK2 receptor antagonists may have a great therapeutic
      potential. In vitro, the cyclopeptide S 16474 (cyclo-[Abo-Asp(D-Trp(Suc0Na)-Phe-N
      (Me)Bzl)]) bound to both human tachykinin NK1 and NK2 receptors expressed in two
      lines of transfected Chinese hamster ovary cells (IC50 values 85 nM and 129 nM,
      respectively), while showing a poor affinity for the rat tachykinin NK1 receptor.
      S 16474 inhibited the contractions induced by substance P in isolated rabbit vena
      cava (pA2 7.0) and by neurokinin A in rabbit pulmonary artery (pA2 5.6). In vivo
      in anaesthetized guinea-pigs, S 16474 was found to dose dependently inhibit the
      bronchoconstrictions induced by intravenously administered substance P,
      neurokinin A and capsaicin. Plasma extravasation evoked in bronchi by
      endogenously released tachykinins under vagus nerve stimulation was abolished by
      S 16474 (10 mu mol/kg i.v.). These results demonstrate clearly that S 16474 is a
      tachykinin receptor antagonist exhibiting, in vitro and in vivo, a dual
      inhibitory effect on NK1 and NK2 receptors.

PMID- 8750734
TI  - The subsensitivity of striatal glutamate receptors induced by chronic haloperidol
      in rats.
AB  - The aim of the present study was to investigate the influence of chronic
      treatment with haloperidol on the contralateral head turns and rotations induced
      by intrastriatal agonists of NMDA and non-NMDA receptors in rats. N-Methyl-D
      aspartate (NMDA, 500 ng/0.5 mu l), alpha-amino-3-hydroxy-5-methyl-4-isoxasole
      propionic acid (AMPA, 1000 ng/0.5 mu l) or kainic acid (50 ng/0.5 mu l), injected
      into the intermediate and caudal parts of the caudate-putamen, induced
      contralateral head turns and rotations. Haloperidol was given to animals in a
      dose of ca. 1 mg/kg per day in drinking water for 6 weeks. On day 5 of
      withdrawal, haloperidol decreased the number of contralateral head turns, but did
      not significantly influence the contralateral rotations induced by NMDA, AMPA and
      kainic acid. At the same time, haloperidol enhanced the stereotypy induced by
      apomorphine (0.25 mg/kg s.c.). The present results seem to suggest that, apart
      from supersensitivity to dopamine, chronic treatment with haloperidol also
      induces subsensitivity of striatal NMDA and non-NMDA receptors.

PMID- 8750735
TI  - Selectivity of action of staurosporine on Ca2+ movements and contractions in
      vascular smooth muscles.
AB  - We examined the effects of staurosporine, a protein kinase inhibitor, on Ca2+
      movements and contractions due to KCl and 12-deoxyphorbol 13-isobutyrate (DPB),
      which are thought to activate myosin light chain kinase and protein kinase C,
      respectively. In rabbit aortae, staurosporine inhibited contractions due to KCl
      (65.4 mM) and DPB (1 mu M) with IC50 values of 140.5 +/- 1.3 nM and 13.3 +/- 1.3
      nM, respectively. Calphostin C, a putative inhibitor of protein kinase C,
      inhibited DPB-induced contraction with much less effect on the KCl-induced one.
      On the other hand, wortmannin, an inhibitor of myosin light chain kinase, was 4
      times more potent on KCl-induced contraction than the DPB-induced one.
      Staurosporine at 100 nM decreased the rise in cytosolic Ca2+ due to KCl, whereas
      wortmannin did not affect it. In rabbit cerebral arteries permeabilized with beta
      escin, staurosporine at 100 nM, but not 30 nM, inhibited Ca2+ -induced
      contraction in the presence of 1 mM ATP. The results indicate that staurosporine
      preferentially inhibits a contraction dependent on protein kinase C than that
      dependent on myosin light chain kinase in vascular smooth muscles. Its ability to
      inhibit KCl-induced contraction involves inhibition of voltage-dependent Ca2+
      channels.

PMID- 8750736
TI  - L-N6-(1-iminoethyl)-lysine potently inhibits inducible nitric oxide synthase and
      is superior to NG-monomethyl-arginine in vitro and in vivo.
AB  - L-N6-(1-iminoethyl)-lysine is a novel inhibitor of nitric oxide (NO) synthase,
      which similar to aminoguanidine but unlike NG-monomethyl-L-arginine is 30-fold
      more selective for the inducible than for the constitutive isoform of the enzyme.
      Here, we characterized this inhibitor for the first time in intact cells and
      during infection of mice with a NO-sensitive parasite (Leishmania major). L-N6-(1
      iminoethyl)-lysine potently inhibited the activity of inducible NO-synthase in
      primary macrophages. After stimulation by interferon-gamma the IC50 of L-N6-(1
      iminoethyl)-lysine was 0.4 +/- 0.1 mu M and 10- or 30-fold lower than that of NG
      monomethyl-L-arginine or aminoguanidine, respectively. In vivo, L-N6-(1
      iminoethyl)-lysine (0.4-9 mM in the drinking water) suppressed inducible NO
      synthase activity and caused a dramatic exacerbation of leishmaniasis, despite a
      counterregulatory increase of inducible NO-synthase protein in the tissue. In
      contrast, considerably higher concentrations of NG-monomethyl-L-arginine (20-50
      mM) were required in order to achieve comparable effects. NG-monomethyl-L
      arginine, but not L-N6-(1-imino-ethyl)-lysine led to weight loss, reduced water
      and food consumption. We conclude that L-N6-(1-iminoethyl)-lysine should be used
      instead of NG-monomethyl-L-arginine for potent suppression of inducible NO
      synthase in vitro and in vivo.

PMID- 8750737
TI  - sigma1 Receptors in rat striatum regulate NMDA-stimulated [3H]dopamine release
      via a presynaptic mechanism.
AB  - The role of the sigma1 receptor in the regulation of N-methyl-D-aspartate (NMDA)
      stimulated [3H]dopamine release from rat striatal slices was examined. The sigma
      receptor agonist 1S,2R-(--)-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1
      pyrrolidinyl)cy clohexylamine (BD737) inhibited stimulated release in a
      concentration-dependent manner. The sigma1 receptor antagonist, 1
      (cyclopropylmethyl)-4-(2'-(4"-fluorophenyl)-2'-oxoethyl)piperidi ne HBr (DuP
      734), reversed inhibition of release by BD737. Haloperidol, di-o-tolylguanidine
      (DTG) and N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine
      (BD1008) reversed the BD737-mediated inhibition of release. Haloperidol and DTG
      also antagonized inhibition of stimulated release by (+)-pentazocine.
      Furthermore, BD737 and (+)-pentazocine inhibited stimulated release in the
      presence of tetrodotoxin, suggesting that sigma1 receptors regulating dopamine
      release are located on dopaminergic nerve terminals. These data suggest that
      sigma1 receptors may be important in the regulation of glutamate-stimulated
      dopamine release.

PMID- 8750738
TI  - Chronic forced swim stress of rats increases frontal cortical 5-HT2 receptors and
      the wet-dog shakes they mediate, but not frontal cortical beta-adrenoceptors.
AB  - We studied the effects of chronic forced swim stress on 5-HT2 receptors and beta
      adrenoceptors in the rat frontal cortex. The number of 5-HT2 receptors was
      increased immediately after the last chronic stress, but not after an acute
      stress. In vivo, the number of wet-dog shakes induced by a 5-HT2 receptor
      agonist, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), was increased
      24 h after the last chronic stress. However, the concentrations of 5-HT and 5
      hydroxyindole acetic acid (5-HIAA), measured by high pressure liquid
      chromatography (HPLC), were not altered by this stress. Binding sites for [3H]CGP
      12177, i.e., beta-adrenoceptor sites, were unchanged after both the acute and the
      chronic stress. These results suggest that, in the rat, the chronic forced swim
      stress increases the number of frontal cortical 5-HT2 receptors and the number of
      wet-dog shakes mediated by these receptors, while the number of frontal cortical
      beta-adrenoceptors is not increased by this treatment.

PMID- 8750739
TI  - alpha1-Adrenoceptor subtypes mediating antinatriuresis in Wistar and stroke-prone
      spontaneously hypertensive rats.
AB  - This study examined the alpha1-adrenoceptor subtypes involved in mediating
      adrenergically induced Na+ reabsorption in the kidney of pentobarbitone
      anaesthetised Wistar and stroke-prone spontaneously hypertensive rats (SHRSP).
      Close renal-arterial phenylephrine (50-100 mu g kg-1 h-1) administration in
      Wistars, with regulated renal perfusion pressure, caused small reductions in
      renal haemodynamics but large reductions, of 35%, 64% and 57% (all P < 0.05), in
      urine volume, absolute and fractional Na+ excretions. The magnitude of these
      excretory responses to phenylephrine were similar in the presence of the alpha1B
      adrenoceptor alkylating agent, chloroethylclonidine (10 mu g kg-1 h-1), but were
      blocked during administration of the alpha1A-adrenoceptor antagonist, 5
      methylurapidil (10 mu g kg-1 h-1). Phenylephrine infusion in the stroke-prone
      spontaneously hypertensive rats caused changes in renal haemodynamics and fluid
      excretion of comparable magnitude to that achieved in Wistars which was blocked
      by 5-methylurapidil but not chloroethylclonidine. These observations suggest that
      in Wistar and stroke-prone spontaneously hypertensive rats the adrenergically
      induced Na+ reabsorptive responses are mediated by alpha1A-adrenoceptors.

PMID- 8750740
TI  - Influence of the 21-aminosteroid U74389F on ischemia-reperfusion injury in the
      rat.
AB  - We examined the effects of the administration of 21-[4-(2,6-di-1-pyrrolidinyl-4
      pyrimidinyl)-1-piperazinyl]-pregna-1,4,9( 11)-triene-3,20-dione,
      monomethansulfonate (U74389F), a 21-aminosteroid and so-called lazaroid, that is
      characterized by an inhibitory activity against iron-dependent lipid
      peroxidation, on ischemia-reperfusion renal injury in a rat model. After either
      60 or 90 min of ischemia, plus 2 or 24 h of reperfusion, kidneys were assayed for
      glutathione, adenine nucleotides and lipid peroxidation products. 60 min of
      ischemia produced too little oxidative stress and/or too much spontaneous
      recovery to allow visualization of the protective effect of the drug. 90 min of
      ischemia followed by reperfusion induced significant glutathione oxidation, the
      free oxidized glutathione to total glutathione redox ratio (%) being enhanced
      from 4.6 +/- 0.7% before kidney clamping to 11 +/- 1 and 8.6 +/- 1.4% at 2 and 24
      h reperfusion, respectively. Treatment with the lazaroid provided significant
      protection against this oxidation (4.9 +/- 1.05% at 24 h reperfusion). Results of
      lipid peroxidation confirmed the antioxidant effect of the lazaroid. In
      conclusion this study provides evidence for a protective role of the tested
      lazaroid against ischemia-reperfusion renal injury in the rat.

PMID- 8750741
TI  - The role of 5-HT1D and 5-HT1A receptors in mediating 5-hydroxytryptophan induced
      myoclonic jerks in guinea pigs.
AB  - Systemic administration of 5-hydroxytryptophan (5-HTP) to guinea pigs causes
      species-specific, rhythmic, whole body jerks (myoclonic jerks), the frequency and
      amplitude of which were measured in an automated apparatus. The brain penetrant 5
      HT1D receptor agonist 3-(2-dimethylaminoethyl)-4-chloro-5-propoxyindole
      hemifumarate (SKF 99101H) (3-30 mg/kg i.p.) and the selective 5-HT1A receptor
      agonist (+/-)8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.3-3 mg/kg
      s.c.) dose dependently potentiated the frequency and intensity of myoclonic jerks
      caused by 5-HTP (100 mg/kg). Cotreatment of guinea pigs with 8-OH-DPAT (3 mg/kg
      s.c.) and SKF 99101H (30 mg/kg i.p.), which were inactive when given alone, gave
      a marked myoclonic jerk response. Conversely, the myoclonic jerk response to
      higher doses of 5-HTP (150 mg/kg i.p.) was dose dependently blocked by the 5-HT1D
      receptor antagonist GR 127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'
      methyl-4'-(5-methyl-1 ,2,4-oxadiazol-3-yl)[1,1'-biphenyl]4-carboxamide oxalate)
      (ED50 0.32 mg/kg i.p.) and the selective 5-HT1A receptor antagonist WAY 100635 (N
      [2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)
      cyclohexanecarboxamide trihydrochloride) (ED50 0.33 mg/kg i.p.). The response to
      5-HTP (150 mg/kg i.p.) was also blocked by ritanserin (0.01-0.3 mg/kg i.p.). Our
      data therefore confirm previous reports concerning the effects of 5-HT2A/2C
      receptor blockade on 5-HTP induced myoclonic jerks and suggest that both 5-HT1D
      and 5-HT1A receptors play an important role in mediating this behavioural
      response.

PMID- 8750742
TI  - Dexamethasone influences intimal thickening and vascular reactivity in the rabbit
      collared carotid artery.
AB  - Intimal thickening predisposes to atherosclerosis and is often associated with
      alterations of the vascular reactivity of the artery. We investigated whether
      dexamethasone inhibited the intimal thickening and reactivity changes induced by
      a silicone collar placed around the left rabbit carotid artery for 2 weeks. The
      sham-operated, right artery served as control. Dexamethasone (1 mg/kg/day), given
      in the drinking water (n = 10) or by a subcutaneous minipump (n = 10), abolished
      intimal thickening compared to that of both placebo groups (n = 10). Both
      dexamethasone and the collar suppressed the isometric force development of
      isolated segments elicited by KCl in organ chamber experiments. The collar raised
      the sensitivity to serotonin (5-hydroxytryptamine, 5-HT) and the maximum force
      development (Emax) after normalization for the KCl responses. Dexamethasone
      exerted complex effects on 5-HT contractions in sham arteries: the curves often
      became biphasic, and sensitivity and Emax of the first phase were depressed by
      dexamethasone. In contrast, dexamethasone raised the hypersensitivity of collared
      arteries to 5-HT even further. Collar and dexamethasone did not influence
      endothelium-dependent relaxations elicited by acetylcholine or the calcium
      ionophore A-23187. It is concluded that dexamethasone interfered with neo-intima
      formation in the collar model, presumably by inhibition of smooth muscle cell
      migration and/or proliferation, without restoring contractile behaviour.
      Therefore, the collar-induced alterations in the reactivity of the smooth muscle
      cells in the media appear to be unrelated to the process of intimal thickening.

PMID- 8750743
TI  - Inhibition of the vasopressin-enhancing effect on memory retrieval and relearning
      by a vasopressin V1 receptor antagonist in mice.
AB  - We have previously shown that [Arg8]vasopressin bilaterally administered into the
      ventral hippocampus of mice at a dose of 0.025 ng/animal 10 min prior to the
      retention session, improved long-term retrieval processes and relearning of a Go
      No-Go visual discrimination task. The purpose of the present study was to
      determine whether the vasopressin V1 receptor antagonist, -beta-mercapto
      beta,beta-cyclopentamethylenepropionyl1, O-Me-Tyr2,Arg8]vasopressin,
      d(CH2)5Tyr(Me)vasopressin), is able to block the behavioral effect of arginine
      vasopressin in the ventral hippocampus. We first tested the effect of three doses
      of d(CH2)5Tyr(Me)vasopressin (0.025, 1, and 6.3 ng/animal) in the same
      experimental conditions as used for arginine-vasopressin. The results showed a
      dose-dependent deleterious effect of the vasopressin V1 receptor antagonist on
      retrieval and relearning, suggesting the involvement of endogenous arginine
      vasopressin in the ventral hippocampus for these memory processes. Second, we
      tested the ability of d(CH2)5Tyr(Me)vasopressin to block the enhancing effect of
      experimentally administered arginine-vasopressin. The antagonist was injected at
      a dose of 0.025 ng, which had no intrinsic effect on behavior, or at a dose of 1
      ng, which had a weak deleterious effect on behavior, followed by administration
      of 0.025 ng of arginine-vasopressin. The results showed that even at the weakest
      dose (0.025 ng), d(CH2)5Tyr(Me)vasopressin blocked the enhancing effect of
      arginine-vasopressin on retrieval and relearning. Thus, as for other behaviors
      and structures, the antagonist microinjected into the ventral hippocampus
      prevents the enhancing effect of arginine-vasopressin on long-term retrieval and
      relearning. However, the exclusive involvement of the vasopressin V1 receptors
      remain to demonstrate vis-a-vis oxytocin receptors.

PMID- 8750744
TI  - Intermittent morphine treatment causes long-term desensitization of functional
      dopamine D2 receptors in rat striatum.
AB  - 3 weeks following cessation of intermittent morphine administration (10 mg/kg,
      s.c., once daily for 14 days), [3H]dopamine and [14C]acetylcholine release
      induced by 10 microM N-methyl-D-aspartate (NMDA) from superfused rat striatal
      slices appeared to be significantly higher than the release from striatal slices
      from saline-treated rats. A similar adaptive increase of the NMDA-evoked release
      of these neurotransmitters was observed in slices of the nucleus accumbens,
      whereas that of [3H]noradrenaline from hippocampal slices remained unchanged.
      Blockade of dopamine D2 receptors by 10 microM (--)-sulpiride enhanced NMDA
      induced [3H]dopamine and [14C]acetylcholine release from striatal slices from
      saline-treated animals, but was found to be ineffective in this respect following
      intermittent morphine treatment. Moreover, morphine administration appeared to
      cause a profound decrease in the apparent affinity of the full dopamine D2
      receptor agonist LY171555 (quinpirole) for these release-inhibitory dopamine D2
      receptors, indicating the occurrence of dopamine D2 receptor desensitization. It
      is suggested that such a desensitization of dopamine D2 receptors on dopaminergic
      nerve terminals as well as on cholinergic interneurons may play a pivotal role in
      the long-lasting nature of behavioural sensitization upon cessation of treatment
      with morphine and possibly other drugs of abuse.

PMID- 8750745
TI  - Characterization of muscarinic receptor and beta-adrenoceptor interactions in
      guinea-pig oesophageal muscularis mucosae.
AB  - Smooth muscles of a number of species contain both muscarinic M2 and M3 receptors
      in differing proportions and while muscarinic M3 receptors mediate contraction,
      the role of muscarinic M2 receptors is unclear. Muscarinic M2 receptor-mediated
      inhibition of adenylyl cyclase activity has been demonstrated in smooth muscle
      and since beta-adrenoceptor relaxation of this tissue is mediated via stimulation
      of adenylyl cyclase, an interaction between muscarinic M2 receptors and beta
      adrenoceptors in smooth muscle has been postulated. Such an interaction has been
      demonstrated in guinea-pig ileum and trachea using two different approaches. The
      present study investigates whether interactions between muscarinic M2 receptors
      and beta-adrenoceptors also occur in guinea-pig oesophageal muscularis mucosae.
      Using the technique of selective muscarinic M3 receptor alkylation, we were
      unable to demonstrate muscarinic M2 receptor-mediated re-contractions in
      oesophageal smooth muscle, as described previously in ileum. In addition, while
      increased functional antagonism of relaxant responses to isoprenaline could be
      demonstrated in tissues pre-contracted with oxotremorine M compared to histamine,
      muscarinic M2 receptor activation did not contribute to this effect, as described
      previously in trachea. These data suggest a lack of interaction between
      muscarinic M2 receptors and beta-adrenoceptors in guinea-pig oesophageal smooth
      muscle, but suggest an interaction between muscarinic M3 receptors and beta
      adrenoceptors.

PMID- 8750746
TI  - Serotonin outflow in the hypothalamus of conscious rats: origin and possible
      involvement in cardiovascular control.
AB  - The push-pull technique was used to investigate the effects of neuroactive
      compounds and experimentally induced blood pressure changes on the release of
      endogenous serotonin in the posterior hypothalamic area of the rat. Hypothalamic
      superfusion with artificial cerebrospinal fluid which contained 80 mM K+ or 1
      microM veratridine enhanced the rate of serotonin release. Superfusion with
      tetrodotoxin (5 microM) led to a pronounced decrease in the serotonin release
      rate. Increases in blood pressure elicited by intravenous infusions of
      noradrenaline (3-4 micro g/kg/min) or phenylephrine (10 microg/kg/min) enhanced
      the release of serotonin in the hypothalamus. Similarly, the serotonin release
      rate was enhanced by hypervolaemia. Decreases in blood pressure elicited by
      intravenous administration of nitroprusside (30-40 microg/kg/min) or
      chlorisondamine (3 mg/kg) reduced the release of serotonin. Likewise, the
      serotonin release rate was decreased by hypovolaemia. With one exception
      (hypothalamic superfusion with tetrodotoxin) neither neuroactive drugs, nor
      experimentally elicited blood pressure changes modified the release rate of the
      metabolite 5-hydroxyindoleacetic acid (5-HIAA). These findings show that changes
      in blood pressure lead to counteractive alterations in the release of serotonin.
      Thus, serotoninergic neurons of the posterior hypothalamus seem to be involved in
      the homeostasis of blood pressure by exerting a hypotensive function. At least in
      the hypothalamus, the concentration of 5-HIAA in the superfusate does not seem to
      be a reliable marker for the activity of serotoninergic neurons.

PMID- 8750747
TI  - Cardiovascular effects of gamma-MSH/ACTH-like peptides: structure-activity
      relationship.
AB  - Intravenous administration of gamma2-melanocyte-stimulating hormone (gamma2-MSH)
      to conscious rats causes a dose-dependent increase in blood pressure and heart
      rate, while the structurally related peptide adrenocorticotropic hormone-(4-10)
      (ACTH-(4-10)) is 5-10 times less potent in this respect. This prompted us to
      investigate which amino acid sequence is determinant for the cardiovascular
      selectivity of peptides of the gamma-MSH family. Lys-gamma2-MSH, most likely the
      endogenously occurring gamma-MSH analog, was as potent as gamma2-MSH in inducing
      increases in blood pressure and heart rate. Removal of C-terminal amino acids
      resulted in gamma-MSH-fragments which were devoid of cardiovascular activities.
      Removal of amino acids from the N-terminal side of gamma2-MSH resulted in
      fragments which were less potent, but had an intrinsic activity not different
      from that of gamma-MSH. Surprisingly, gamma-MSH-(6-12) was more potent than
      gamma2-MSH. The shortest fragment which displayed pressor and tachycardiac
      responses was the MSH 'core', His-Phe-Arg-Trp (= gamma-MSH-(5-8)), which is
      identical to ACTH-(6-9). This was corroborated by testing fragments of ACTH-(4
      10). We conclude that the message essential for cardiovascular effects resides in
      the gamma-MSH-(5-8)/ACTH-(6-9) sequence. Proper C-terminal elongation is required
      for full expression of cardiovascular activity of gamma2-MSH, as the sequence of
      Asp9-Arg10-Phe11 appears to play an important role in establishing intrinsic
      activity. The amino acids N-terminal to the MSH 'core' sequence appear to be
      essential for the potency of the peptides.

PMID- 8750748
TI  - Dose-response relationship between smoking and impairment of hearing acuity in
      workers exposed to noise.
AB  - The study included an inquiry and clinical examination of 443 reindeer herders
      (mean age 43 years) who frequently used noisy tools and vehicles, in particular
      snowmobiles and chain-saws. Age-adjusted hearing thresholds at 3 and 4 kHz
      deteriorated significantly with increased exposure to noise. There was the dose
      response relationship between the amount of smoking and the impairment of hearing
      acuity when exposure time to noise was used as covariance. The amount of smoking
      was not significant until very heavy smoking (more than 144,000 cigarettes, i.e.
      20 cigarettes/day for more than 20 years), and no smoking effect could be seen
      using the classification of current smoking habits. The results support the
      practice that screening of hearing acuity should be repeated more often in
      smokers than in non-smokers in noisy work so that hearing damage can be found in
      an incipient stage and noise-induced hearing loss effectively prevented.

PMID- 8750749
TI  - Reliable clinical determination of speech recognition scores using Swedish PB
      words in speech-weighted noise.
AB  - Results of speech recognition tests with competing sound obtained by the use of
      standard audiometric equipment will suffer from considerable systematic errors
      because of normal calibration variability. To avoid this, and to keep the
      reliability high, not only in investigative situations but also in clinical
      practice, it is highly recommended that test materials be used with speech and
      noise mixed in the recording. Considering this, a test material was developed
      consisting of six Swedish PB word lists and speech-weighted noise pre-mixed with
      a fixed speech-to-noise ratio and recorded on compact disc. This material was
      investigated for list equality, and normative recognition data were obtained. The
      material was found to be reliable and suitable for clinical use.

PMID- 8750750
TI  - Hearing-aid fitting in profoundly hearing-impaired children. Comparison of
      prescription rules.
AB  - Generally, the performance of a hearing-impaired child with his or her hearing
      aids is the major criterion in selection programmes for cochlear implantation.
      Thereto, it has to be considered whether the hearing-aid fitting is optimal. For
      this purpose, methods which prescribe hearing-aid gain are valuable, especially
      in young preverbal children. Three of these methods were evaluated by comparing
      the calculated and measured gain as a function of frequency in a selected group
      of profoundly hearing-impaired children (n = 16), all of whom were successful
      users of hearing aids. Fair agreement was found for the modified NAL rule
      applicable in profoundly hearing-impaired subjects and the DSL method (desired
      sensation level method).

PMID- 8750751
TI  - Application of cross-correlation function in the evaluation of objective MLR
      thresholds in the low and middle frequencies.
AB  - In this study, the cross-correlation function was applied in the evaluation of
      MLR thresholds in the low and middle frequencies. The parameters of the cross
      correlation function consist of the correlation coefficient at a lag-time of zero
      (RO), the maximum correlation coefficient (RM), and the latency delay on the lag
      time axis at the point of the maximum correlation coefficient (DL). The normal
      limits of the parameters of cross-correlation at the MLR threshold level, which
      was identified by visual detection across frequencies, were obtained in normal
      hearing and hearing-impaired subjects. The cross-correlation functions for two
      traces were also performed below threshold level. All cross-correlation
      parameters (RO, RM and DL) below threshold level were outside normal limits in
      91% of all the subjects. The incidence of the only RM or DL parameter value
      within normal limits was 6% or 3% of all cases at the subthreshold level.
      Correlation data allow precise measurements of the MLR threshold and enhance the
      sensitivity of the definition of the MLR threshold. In addition, our study
      provides quantifiable information for estimating MLR threshold.

PMID- 8750752
TI  - Prevalence of childhood hearing impairment in southern Finland.
AB  - The Department of Audiology in Helsinki University Central Hospital provides
      paedoaudiological services for the Province of Uusimaa, including Helsinki. Our
      purpose was to study the prevalences of hearing threshold loss in children born
      in the period 1973 to 1990. The material consisted of 353 hearing-disabled
      children. The pure-tone average (0.5, 1 and 2 kHz) of the better ear was the
      parameter for hearing threshold. In 36 subjects the hearing acuity was determined
      with the behavioural observation test or the brainstem electric response
      measurement. The number of hearing-impaired per birth year (hearing level > or =
      35 dB) ranged from 6 to 30 and the prevalence rate from 0.3 to 1.9 in 1000,
      totalling 1.1. After matching the hearing-impairment criteria with those of the
      previous reports from northern Sweden, Denmark and the European Community, we
      were able to compare the prevalences.

PMID- 8750753
TI  - The long-term effect of early telephone intervention on hearing aid success.
AB  - The purpose of the study was to determine if subjects who were contacted by
      telephone periodically during the first 3 months following hearing-aid dispensing
      would report greater satisfaction, more frequent hearing aid use, and fewer
      complaints at one year postdispensing than subjects who were not contacted
      frequently. Subjects were 55 hearing-impaired adults who purchased aids, 27 of
      whom were contacted periodically by phone. Results revealed that frequent
      telephone contact in the period soon after dispensing does not appear to be an
      effective mass management tool in this population, although its value cannot be
      ruled out for some types of clients.

PMID- 8750754
TI  - Aspects of short-term auditory memory as revealed by a recognition task on multi
      tone sequences.
AB  - Retention capacity and temporal aspects of auditory short-term memory have been
      investigated through a multi-tone sequence paradigm and recognition task. There
      were 37 normally hearing subjects, with (16) and without (21) musical education.
      They were required to judge whether or not a tonal sequence comprised a tone
      probe, which was presented following the sequence. The subjects' performance
      appears to be mainly dependent on the number of the sequence components (n =
      2,4,6), while sequence-probe interval (1,3,7 sec) represents a factor of minor
      weight. In addition, a strong recency effect has been shown for the last sequence
      component, also extending to the antecedent ones when sequence-probe interval is
      short. In contrast to studies on verbal short-term memory, no primacy effect has
      been demonstrated. Musically experienced subjects performed significantly better
      than naive counterparts. These results have proved to be repeatable in separate
      groups of subjects, and sensitive to auditory skills associated with musical
      practice. It is likely that tests of auditory memory based on tonal sequences
      could be useful in the clinical assessment of subjects with suspected central
      auditory dysfunction, or subjects who have had a cochlear implant after variable
      periods of auditory deprivation.

PMID- 8750755
TI  - Loudness discomfort levels and saturation levels in hearing aids prescribed for
      young persons.
AB  - Hearing aids were re-evaluated for 18 persons aged 11-16 years. Since these aids
      were fitted mainly using an informal test of aided loudness discomfort, the
      saturation levels were re-evaluated with a new magnitude-estimation procedure for
      measuring unaided and aided loudness discomfort levels. Sixteen subjects had used
      hearing aids capable of producing uncomfortably loud warble tones. New hearing
      aids were fitted according to the new loudness discomfort data and the NAL
      recommendation for insertion gain. When forced to choose between the previously
      prescribed hearing aids and the new aids after three weeks of real life
      comparison, most subjects preferred the new instruments, but three persons
      finally decided to wear hearing aids with saturation levels exceeding their
      loudness discomfort levels. The magnitude estimation procedure was found to be
      clinically feasible, although problems with the instruction caused uncertainty in
      some cases. Measured loudness discomfort levels increased 5-10 dB between test
      and retest sessions.

PMID- 8750756
TI  - Frequency specificity of ABRs.

PMID- 8750757
TI  - Bedside glucose monitoring: can it be a real, alternative in the daily hospital
      routine.

PMID- 8750758
TI  - Evaluation of bedside blood glucose monitoring by the phlebotomy team in an acute
      general care hospital.
AB  - A feasibility study was undertaken to evaluate laboratory phlebotomists
      performing bedside glucose monitoring (BGM) over a 3-month period on a medical
      and surgical floor. Specific questions included: feasibility of providing testing
      on a 24-h basis, accuracy, appropriate utilization, effect on patient care, and
      an analysis of cost. In all, 1975 tests were performed on 114 patients. BGM
      results were within 15% of the laboratory's result 97% of the time. Patient and
      physician satisfaction was high. Although the cost of BGM is slightly higher than
      a laboratory glucose test, its use appeared to reduce the length of hospital stay
      by 0.47 days. Practical information on initiating a highly successful BGM program
      is provided.

PMID- 8750759
TI  - Impact of metabolic activity of beta cells on cytokine-induced damage and
      recovery of rat pancreatic islets.
AB  - The influence of beta cell activity on cytokine-induced functional and structural
      impairments as well as the ability of those damaged cells to recover were
      investigated. Rat islets cultured for 4 days in the presence of 5, 10, and 30
      mmol/l glucose were exposed to interferon-gamma (IFN, 500 U/ml) and tumor
      necrosis factor-alpha (TNF, 250 U/ml) for the last 24 h. After cytokine removal
      islets were allowed to recover spontaneously in culture medium containing 10
      mmol/l glucose for a further 7 days. Cytokines significantly inhibited insulin
      release into culture medium, insulin storage, glucose-stimulated insulin
      secretion, protein, and DNA synthesis. In the presence of cytokines there was a
      six- to eightfold increase in nitrite production by the islets. The functional
      impairments were more pronounced in metabolically stimulated beta cells. In
      addition, cytokines caused membrane alterations as indicated by increased
      spontaneous chromium-51 release. The cytokines specifically induced the synthesis
      of two proteins (72 and 88 kDa, respectively). By immunoblotting, the 72-kDa
      protein was identified as heat shock protein. After a 1-week recovery period,
      insulin storage and stimulated insulin secretion of cytokine-treated islets were
      still significantly diminished. However, protein and DNA synthesis of cytokine
      exposed islets returned to pre-exposure levels. In conclusion, high beta cell
      activity increases islet susceptibility to TNF+IFN. Cytokine-induced, long
      lasting, inhibitory effects are primarily directed to beta-cell-specific
      functions, while general vital cell functions clearly recover after cytokine
      removal. The induction of certain proteins and the increased protein synthesis
      and replication rate after cytokine removal might reflect activated repair
      processes.

PMID- 8750760
TI  - Renal growth during pregnancy in insulin-dependent diabetic women. A prospective
      study of renal volume and clinical variables.
AB  - Kidney volume was measured during pregnancy in insulin-dependent diabetic women
      by an ultrasound technique and prognostic value of these measurements evaluated.
      A prospective study was performed on 87 pregnant women with insulin-dependent
      diabetes attending the maternity clinic of Aarhus Kommunehospital. Patients with
      proliferative retinopathy alone, hydronephrosis, or nephrotic syndrome were
      excluded. The patients were grouped according to onset and duration of diabetes
      and to vascular lesions; group I (n = 35, White class B+C), group II (n = 11,
      White class D0), group III (n = 26, White class D+), and group IV (n = 15, White
      class F+F/R). The patients visited the hospital every 2 weeks during pregnancy
      for general obstetric and glycaemic control and blood sampling. The volume of
      both kidneys was measured by a computerized nephrosonograph during the three
      terms of pregnancy, the puerperium and 4 months postpartum. The kidney volume
      increased significantly in all four groups from first to third trimester. In the
      third trimester the kidney volumes were 375 +/- 68 ml (I), 341 +/- 50 ml (II),
      362 +/- 63 ml (III), and 343 +/- 54 ml (IV). The kidney volume in the third
      trimester was positively correlated with creatinine clearance (r = 0.33, P <
      0.01) and inversely correlated with creatinine in serum (r = -0.27, P = < 0.02).
      Total kidney volume decrease (in percent) defined as the difference of maximal
      volume and value at 4 months postpartum was inversely correlated to albuminuria
      in the third trimester (r = -0.25, P < 0.05) and vascular lesions of the
      patients: (mean +/- SEM) 37 +/- 4% (I), 25 +/- 7% (II), 19 +/- 5% (III), and 11
      +/- 7% (IV), P < 0.01. In the puerperium, kidney volume decreased significantly
      from third trimester in groups I, II, and III, whereas we observed no change in
      group IV. Six of 15 women in groups II and III with kidney volume < 300 ml and
      normoalbuminuria in the first trimester developed persistent microalbuminuria
      after pregnancy (P < 0.02). The renal volume in insulin-dependent diabetic women
      increases significantly during pregnancy and is inversely related to the vascular
      lesions of the patients. The decrease in renal volume after pregnancy is related
      to the albuminuria at the end of pregnancy. Women with longstanding diabetes,
      White class D (= groups II+III), and kidney volume < 300 ml in the first
      trimester have a high risk of developing permanent microalbuminuria after
      pregnancy.

PMID- 8750762
TI  - Glucose metabolism and left ventricular dysfunction are normalized by insulin and
      islet transplantation in mild diabetes in the rat.
AB  - The aim of the present experimental study in the rat heart was to assess cardiac
      performance and metabolism in mild diabetes of 2 months' duration (postprandial
      blood sugar levels of 307 +/- 101 mg/dl and nearly normal fasting blood glucose
      of 102 +/- 40 mg/dl) using the working rat heart model at physiological workload
      with a perfusion time of 60 min. We also compared the effect of two forms of
      therapy for diabetes, islet transplantation and insulin therapy (s.c.), after 2
      months. A 36% reduction in glucose utilization is metabolically characteristic
      for the diabetic heart, mainly caused by a 55% reduced glucose uptake (P <
      0.001), but also by a nearly twofold increased lactate and pyruvate production (P
      < 0.001). This reduced carbohydrate metabolism is accompanied by a 37% reduction
      of oxygen uptake (P < 0.001) as well as a significant reduction in myocardial ATP
      and CP levels (P < 0.001), resulting in a significantly reduced cardiac output (P
      < 0.001). Moreover, the balance of energy reveals that the diabetic heart obtains
      46% of its energy requirements for 1 h from endogenous glycogen, whereas the
      control heart obtains 91% of its energy needs (i.e. preferentially) from
      exogenous glucose (only 9% from endogenous glycogen). Both investigated
      therapeutic interventions led to a complete reversibility of the hemodynamic and
      metabolic alterations, indicating that the cause of diabetic cardiomyopathy in
      this model of mild and short-term diabetes is due to a defect in cardiac
      carbohydrate metabolism, which is correctable by insulin administration.

PMID- 8750761
TI  - Effect of insulin on renal sodium handling and renal haemodynamics in insulin
      dependent (type 1) diabetes mellitus patients.
AB  - The effects of insulin on renal haemodynamics and renal sodium handling were
      studied in eight insulin-dependent (type 1) diabetic patients (aged 30 +/- 3
      years). Seven healthy men (aged 38 +/- 4 years) served as controls. The type 1
      diabetic patients were resistant to insulin-stimulated glucose disposal as
      estimated by a 45% lower metabolic (P < 0.01) clearance of glucose as compared
      with controls. However, type 1 diabetic patients were still sensitive to the
      distal tubular antinatriuretic effect of insulin, as indicated by an increase in
      distal sodium reabsorption (95.5 +/- 0.5% to 96.9% +/- 0.4%; P < 0.05) during
      insulin infusion compared with controls (95.5% +/- 0.6% to 97.4% +/- 0.3%; P <
      0.05). In control subjects insulin infusion was associated with 9% increases (P <
      0.05) in lithium clearance and in renal plasma flow, whereas no significant
      increases in lithium clearance and in renal plasma flow were observed in the type
      1 diabetic patients. In both groups, the changes in renal plasma flow in response
      to insulin infusion were positively correlated with that in lithium clearance (r
      = 0.80 and r = 0.90, respectively; P < 0.05-0.01). In conclusion, the present
      result demonstrates an intact distal tubular sodium retaining effect in
      conjunction with a blunted decrease in proximal tubular sodium reabsorption
      following insulin infusion, which could be the result of an impaired renal
      vasodilation in type 1 diabetes mellitus.

PMID- 8750763
TI  - Intestinally derived lipoprotein particles in non-insulin-dependent diabetic
      patients with and without hypertriglyceridaemia.
AB  - We have previously demonstrated alterations in apolipoprotein B-48 metabolism in
      the post-prandial state in patients with non-insulin-dependent diabetes mellitus.
      This study investigates the relationship between hypertriglyceridaemia and post
      prandial lipoprotein metabolism. Four groups of patients were examined: non
      insulin-dependent diabetic patients, with normal serum triglyceride levels (serum
      triglyceride < 2.1 mmol l-1; haemoglobin HbA1c 5.5% +/- 0.4%); poorly controlled,
      non-insulin-dependent diabetic patients with hypertriglyceridaemia (serum
      triglyceride > 2.1 mmol l-1; HbA1c 8.8% +/- 0.9%); non-diabetic subjects with
      serum triglycerides < 2.1 mmol l-1; and non-diabetic subjects with
      hypertriglyceridaemia (serum triglyceride > 2.1 mmol l-1). Subjects were studied
      fasting and following a high-fat meal (1300 kcal). The triglyceride-rich
      lipoprotein fraction was isolated by ultracentrifugation (d < 1.006 g ml-1).
      Apoprotein B-48, apoprotein B-100 and apoprotein E were separated on 4%-15%
      gradient gels and quantified as a percentage of the fasting concentration by
      densitometric scanning. Triglyceride-rich lipoprotein apolipoprotein B-48 and
      apolipoprotein B-100 post-prandial profiles demonstrated a maximum increase
      either at 2 h or rising still further to a peak at 6 h before falling in the
      diabetic groups and hypertriglyceridaemic non-diabetic subjects when compared
      with the normotriglyceridaemic control subjects whose levels decreased after 2 h
      (P < 0.05). A significantly different triglyceride-rich lipoprotein
      apolipoprotein E profile was also exhibited by the diabetic patients (P < 0.05).
      Levels of triglyceride-rich lipoprotein, cholesterol, triglyceride, total protein
      and apoprotein B were elevated in the hypertriglyceridaemic subjects, both
      diabetic and non-diabetic. These results indicate that hypertriglyceridaemia is
      associated with altered metabolism and composition of post-prandial triglyceride
      rich lipoprotein particles in both poorly controlled diabetic and non-diabetic
      subjects.

PMID- 8750764
TI  - Apolipoprotein AI-CIII-AIV genetic polymorphisms and coronary heart disease in
      type 2 diabetes mellitus.
AB  - The aim of this study was to verify whether or not the increased prevalence of
      coronary heart disease (CHD) commonly observed in patients with type 2 diabetes
      mellitus is related to a genetic background involving restriction fragment length
      polymorphisms (RFLPs) of apolipoproteins. On the basis of a case-control design,
      62 type 2 diabetic patients with CHD (confirmed by clinical history and
      electrocardiogram) and 62 age- and sex-matched diabetic subjects without CHD were
      enrolled. In each of them RFLPs of the apolipoprotein CIII gene (S1 or S2 allele)
      and AI promoter region (A or G allele), together with fasting plasma lipids and
      apolipoproteins levels, were assessed. The rare S2 allele was found significantly
      (P = 0.05) more frequently in patients with CHD, and its related S1S2 genotype
      was associated with higher plasma levels of total cholesterol (P = 0.01),
      triglycerides (P = 0.007) and apo B (P = 0.001) than the S1S1 genotype. The A
      allele was more frequent (P = 0.004) in patients without CHD and was associated
      with lower plasma cholesterol (P = 0.0001), low-density lipoprotein (LDL)
      cholesterol (P = 0.0001) and apo B (P = 0.005). The S1/A haplotype was more
      frequent (P = 0.05) in patients without CHD and was associated with the lowest
      plasma lipid levels. These results suggest that genetic factors, related to the
      apo AI-CIII-AIV gene cluster, could play a role in the development of CHD in type
      2 diabetic patients, probably through modification of their plasma lipid pattern.

PMID- 8750765
TI  - Quantitation of insulin stores in Langerhans islets by combined
      immunohistochemistry and computerized microspectrophotometric analysis.
AB  - Histology, size, and insulin content of Langerhans islets from normal and recent
      experimental hyperthyroid (REH) dogs were studied. Insulin localization in the
      islets was revealed by immunohistochemistry, and the remaining two variables were
      analyzed by computerized microspectrophotometry according to an original
      technique described here. Observed under the light microscope, the REH dog
      pancreas section shows larger than normal islets whose scarce beta-granules are
      mainly located near B-cell borders and grouped along capillaries. The brown areas
      occupied by insulin in Langerhans islets from REH and normal dogs (mean +/- SEM)
      are 5182 +/- 311 and 4236 +/- 287 microns2, the total mean insulin amount per
      respective islet section-as expressed in absorbance arbitrary units-is 1108 and
      1846, and the light absorbances per such area units are 0.214 +/- 0.070 and 0.436
      +/- 0.060, respectively. Measuring these variables in dog and human (large)
      pancreases by the conventional methods successfully used for small pancreases
      would have been technically impossible.

PMID- 8750766
TI  - Angiopathy affects circulating endothelin-1 levels in type 2 diabetic patients.
AB  - To evaluate the role of endothelin-1 (ET-1), a vasoconstrictor and mitogenic
      peptide synthesized by endothelial cells, on the endothelial dysfunction in non
      insulin-dependent diabetic (type 2) patients, we have measured the circulating ET
      1 levels in 25 patients with and without clinically evident vascular
      complications and in a control group. Circulating ET-1 levels were significantly
      higher in diabetic patients with angiopathy than in diabetics without angiopathy
      and in controls (7.02 +/- 2.9 pg/ml vs 4.4 +/- 1.1 pg/ml and 3.08 +/- 0.7 pg/ml,
      respectively; P < 0.001). No difference was demonstrated between diabetic
      patients without angiopathy and controls. These findings suggest that ET-1 may be
      a marker for arterial vascular disease only in patients with overt angiopathy. It
      is unclear whether it participates in the endothelial injury process or it is
      merely released from damaged endothelial cells.

PMID- 8750767
TI  - Epidemiology of known diabetes in Lombardy, north Italy. Clinical characteristics
      and methodological aspects.
AB  - Diabetes epidemiology can benefit in Italy from the large network of outpatient
      diabetic clinics and patients' facilities. A large investigation was carried out
      in 1988, in a certain area of northern Italy, to estimate the prevalence of known
      diabetes. Using four information sources, 4547 distinct patients were identified.
      Through the capture-recapture method we assessed completeness and estimated a
      prevalence of 3.3%. Prevalence of type 1 diabetes was 0.8 per 1000. Italian age
      standardised overall prevalence and developed-world standardised rates were 2.8%
      and 2.6%, respectively. A representative sample of 2358 patients was
      characterised through a standard questionnaire. Women were diagnosed about 6
      years later than men (58.8 +/- 0.4 vs 52.9 +/- 0.4, P < 0.0001), while the
      duration of the disease was very similar in both sexes (9.9 +/- 0.2 vs 9.5 +/-
      0.2). As regards diabetes therapy, 17.2% of the patients were on diet alone,
      62.1% on oral agents and 20.6% on insulin. Among the insulin-treated subjects
      more than half were on adjuvant therapy with tablets, and only 6.2% were treated
      with 3 injections/day. Less than half of all the known diabetic subjects had had
      an ophthalmoscopic examination in the previous 2 years.

PMID- 8750768
TI  - A novel mechanism of glipizide sulfonylurea action: decreased metabolic clearance
      rate of insulin.
AB  - To examine whether sulfonylureas inhibit the metabolic clearance rate (MCR) of
      insulin, 19 healthy young subjects participated in two experiments. In the first
      protocol (n = 10), a 3-h oral glucose load was performed with and without 2 mg of
      glipizide given 30 min before glucose ingestion. The total insulin response was
      60% greater with than without glipizide (5.9 +/- 0.6 vs 3.7 +/- 0.5 microU/ml; P
      < 0.001). However, the total C-peptide responses were virtually identical (4.7 +/
      0.5 vs 4.8 +/- 0.4 nmol/l) in both studies. In the second protocol (n = 9), the
      MCR of insulin was measured during 4-h euglycemic insulin clamps performed with
      and without glipizide. In the study with glipizide, the subjects ingested 5 mg of
      glipizide at 120 min. The steady-state plasma insulin concentration during the
      4th h, i.e., 1-2 h after glipizide ingestion, was significantly higher than
      during the 2nd h, i.e., before glipizide ingestion (99 +/- 22 vs 78 +/- 17
      microU/ml; P < 0.01). In addition, glucose uptake during the 4th h was greater
      (8.0 +/- 1.6 vs 6.4 +/- 1.5 mg/kg.min) and the MCR of insulin was reduced (503 +/
      126 vs 621 +/- 176 ml/m2.min; P < 0.01). We conclude that glipizide augments
      plasma insulin levels both by enhancing its secretion and by decreasing the MCR
      of insulin.

PMID- 8750770
TI  - Heredity and environment in phoneme articulation: hereditary and environmental
      contributions to articulation proficiency.
AB  - Large twin samples and recent applications of multiple regression techniques to
      behavioral genetics methodology makes possible evaluation of genetic and
      environmental contributions to the articulation proficiency of individual
      phonemes. Factor analysis of the articulation scores from 256 MZ and DZ twins and
      124 of their non-twin siblings (all children ranged from 2; 11 to 9; 8 years)
      were conducted to reduce a 50-item articulation test to a more manageable set of
      five articulation factors. The twins' factor scores were then analyzed using
      multiple regression procedures to determine the extent to which the individual
      factors resulted from genetic and/or environmental influences. The /r/ and
      /[symbol: see text], t[symbol: see text], d[symbol: see text]/ factors were found
      to have strong genetic components, while the /l, j, w/ factor was found to be
      strongly influenced by environmental sources of variation.

PMID- 8750769
TI  - Effects of Acipimox on the metabolism of free fatty acids and very low
      lipoprotein triglyceride.
AB  - The mechanism of triglyceride lowering by Acipimox, a nicotine acid analogue, was
      examined in a group of five moderately hypertriglyceridemic male rhesus monkeys.
      Two experiments were designed to examine the effect of the drug on lipid and
      glucose metabolism in nondiabetic, insulin-resistant animals. A single dose of
      Acipimox (8 mg/kg) given with a meal lowered the plasma free fatty acids (FFA)
      significantly at 4 h (0.102 +/- 0.008 vs 0.154 +/- 0.020 g/l; mean +/- SEM; P <
      0.03); however, FFA concentrations returned to control levels at 6 h. Chronic
      administration of Acipimox (16 mg/kg q. i. d.) for 2 months produced a 31%
      reduction in triglyceride concentration (P < 0.05) and a significant decrease in
      low density lipoprotein (LDL)-cholesterol (P < 0.04), without changes in insulin
      action as measured by the hyperinsulinemic euglycemic clamp. Fasting FFA
      concentrations were not significantly altered by chronic treatment (0.163 +/-
      0.013 versus 0.140 +/- 0.034 g/l). Fatty acid metabolic studies indicated
      increases in FFA transport (203.7 +/- 59.1 versus 136.1 +/- 26.6 microEq/min; P <
      0.05), while FFA fractional clearance rate (FCR) was unchanged. Very low density
      lipoprotein triglyceride (VLDL-Tg) metabolic experiments, using [3H]glycerol,
      showed increases in production and FCR with the drug. Increased VLDL-Tg
      clearance, in spite of increased production of VLDL, appears to be the mechanism
      by which triglycerides are lowered upon chronic Acipimox administration.

PMID- 8750771
TI  - Carriers of genetic disorder and the right to have children.

PMID- 8750772
TI  - Incidence of handicaps in multiple births and associated factors.
AB  - This study investigated the degree of risk of handicap in twins, triplets,
      quadruplets and quintuplets and associated factors, and examined the clustering
      tendency of handicaps. The sample was recruited from the Kinki University Twin
      and Higher Order Multiple Birth Registry. This panel consisted of 705 pairs of
      twins (1410 twins), 96 sets of triplets (287 triplets excluding 1 infant death),
      7 sets of quadruplets (27 quadruplets excluding 1 infant death), and 2 sets of
      quintuplets (10 quintuplets), all of whom were born after 1977. The incidence of
      handicap was 3.7% in twins, 8.7% in triplets, 11.1% in quadruplets, and 10.0% in
      quintuplets. The risk of producing at least 1 handicapped child was approximately
      1 in 13 pairs of twins (7.4%), 1 in 4 or 5 sets of triplets (21.6%), and 1 in 2
      sets of quadruplet and quintuplets (50%). There was a significantly higher
      clustering tendency of handicaps in twins and triplets compared with the expected
      frequency calculated from the incidence rate of handicap. Four significant risk
      factors for subsequent handicap were found by logistic regression: gestation
      number, shortening of gestational age, premature rupture of the membrane, and
      toxemia during pregnancy.

PMID- 8750773
TI  - Prenatal weight gain and the birthweight of triplets.
AB  - The objective of this study was to evaluate the association between maternal
      factors, including rates of gestational weight gain before and after 24 weeks'
      gestation, and adequacy of intrauterine growth for gestational age at birth of
      triplets, as a mean Z-score of the triplet set. The study design was a
      retrospective, anonymous, pilot telephone survey of mothers of triplets and an
      historical cohort analysis of their prenatal weight gain records. The statistical
      analyses performed included multiple regression analysis to formulate a model for
      mean triplet Z-score (a measure of birthweight-for-gestational age) and analysis
      of variance to confirm and simplify the components of this model. Factors
      significant in the final model and their beta coefficients included weeks'
      gestation (-0.124, p < 0.0001), rate of gain before 24 weeks' gestation (0.606, p
      = 0.005), and induced conception (-0.404, p = 0.01). Rate of gain > or = 1.5
      lbs/week before 24 weeks was significant in the analysis of variance (p = 0.009).
      Better intrauterine growth for gestational age is achieved in triplet gestations
      with maternal weight gains of > or = 1.5 lbs/week before 24 weeks' gestation.

PMID- 8750774
TI  - The placental cause of fetal growth retardation in twin gestations.
AB  - The retardation of fetal growth in twin as compared to singleton gestations may
      be due to maternal and/or placental factors. The separate birthweights and
      related placental weights of 487 dichorial twin pairs were recorded, and the
      heavier placental weights of firstborns in comparison with second-borns were
      found to be related to the heavier birthweights of firstborns compared to second
      borns. The lighter placental weights of firstborns compared to second-borns were
      found to be related to the lighter birthweights of firstborns compared to second
      borns. Obviously, the placenta itself may may very well be the cause of the
      retardation of fetal growth in twin gestations.

PMID- 8750775
TI  - Self-awareness in monozygotic twins: a relational study.
AB  - This study considers the replies to a 14-item questionnaire, by 27 monozygotic
      (MZ) and 38 dizygotic (DZ) pairs. Another sample consisting of 48 sets of parents
      of twins (24 of whom were MZ and 24 DZ, not necessarily corresponding to the
      couples of twins actually studied) was used, to answer a questionnaire directly
      related the one put to the twin pairs. The results of statistical tests performed
      (canonical correlation and Fisher's discriminant) indicate that only in MZ twins
      does self-awareness outweigh pair-awareness. This does not seem to be related to
      any difference between MZ and DZ twins in the education/upbringing received from
      their parents.

PMID- 8750776
TI  - Accommodating a twin pregnancy: maternal processes.
AB  - The object of this study was to develop a theory of the relationship between a
      mother and her unborn twins using a qualitative grounded theory methodology. Ten
      women participated in interviews during the last trimester of a twin pregnancy
      and again during the early postpartum period. Data provided by these women was
      analysed using the constant comparative method. Two additional informants were
      sampled in order to formulate and verify the tentative theory. For women in this
      study, the findings indicate that mothers from a relationship with their unborn
      twins within the wider context of accommodating the twin pregnancy in their
      lives. A woman accomplishes this process by immediately seeking information about
      twin pregnancy, by making room, in all senses, for two babies instead of one in
      her life, and by appraising her own pregnancy risk. A mother engages in self
      protective behaviors and in behaviors designed to protect the health of her
      unborn twins as a method of coping with the perceived risk of the twin pregnancy
      and with the twin pregnancy itself. As the twin pregnancy progresses, women move
      toward accepting the idea of being pregnant with twins. For women pregnant with
      twins, the birth of two infants confirms the reality of the pregnancy.

PMID- 8750777
TI  - Use of the systems D1S80, D17S30, ApoB, TC11, VWA, and SE33 for zygosity
      determination.
AB  - The usefulness of PCR systems (D1S80, D17S30, ApoB, TC11, VWA, and SE33) is
      discussed. The statistical evaluation shows that these systems--together with
      other systems--are well suited for zygosity testing.

PMID- 8750778
TI  - Improvement of myocardial function and metabolism in diabetic rats by the
      carnitine palmitoyl transferase inhibitor Etomoxir.
AB  - The effect of Etomoxir as a carnitine palmitoyl transferase I-inhibitor was
      investigated in normal and chronic diabetic rats. Etomoxir (18 mg/kg) was given
      daily for 8 days by intraperitoneal injection in order to inhibit the oxidation
      of fatty acids and to increase the metabolism of glucose. This carnitine
      palmitoyl transferase I-inhibitor significantly improved and almost normalized
      the decreased heart function in chronic diabetic rats. Additionally to the
      improvement of ventricular heart function, alterations in the conducting system
      of the diabetic heart were significantly ameliorated. The serum concentrations of
      glucose, glycerol, cholesterol, tricylglycerol, phospholipids, and beta
      hydroxybutyrate were significantly lower in comparison to untreated diabetic
      animals, while the serum concentration of free fatty acids markedly increased. In
      addition to the improvement of ventricular heart function, the carnitine content
      of heart and liver increased in the Etomoxir-treated rats. On the other hand, the
      lipid content of heart and liver increased in the Etomoxir-treated rats. On the
      other hand, the lipid content of heart and liver increased significantly. Thus,
      Etomoxir may be valuable not only as a potential anti-diabetic drug but also as a
      lipid-lowering agent for the treatment of diabetic related dyslipoproteinaemias
      and, in addition, as an agent in the treatment of diabetic cardiomyopathy.
      However, a long-term evaluation of the metabolic consequences of the blocked
      carnitine palmitoyltransferase I is necessary.

PMID- 8750779
TI  - Hepatic lipase secretion in human hepatoblastoma cell line Hep G2 is not related
      to cellular cholesterol homeostasis.
AB  - The human hepatoblastoma cell line Hep G2 releases the enzyme hepatic lipase
      during incubation with heparin. In this study, hepatic lipase activity was
      released by low concentrations of heparin, and the release was linear with time
      for up to about 10 hours. Preincubations of cells with LDL or compactin induced
      marked but differential changes in hepatic lipase secretion, cellular cholesterol
      content and low density lipoprotein receptor activity, suggesting that the
      secretion of hepatic lipase is regulated independently of cholesterol
      homeostasis.

PMID- 8750780
TI  - Should Graves' disease be considered a collagen disorder of the thyroid, skeletal
      muscle and connective tissue?
AB  - Graves' disease comprises hyperthyroidism, ophthalmopathy, pretibial myxedema and
      acropachy, which occur separately or in various combinations. We have used the
      indirect immunofluorescence test to investigate reactivity of sera from patients
      with autoimmune thyroid disorders with and without ophthalmopathy, with porcine
      extra ocular muscle (EOM) and control tissue substrates. Sera from 75% of
      patients with Graves' hyperthyroidism (GH) and ophthalmopathy, which we call
      thyroid-associated opthalmopathy (TAO), contained one or more antibodies reactive
      with EOM compared to 32% of those with GH without the eye disorder, 41% of
      patients with Hashimoto's thyroiditis (HT), and 16% of normals. Antibodies
      reactive with an EOM connective tissue antigen(s), seen as fluorescence of the
      interstitium and endomysium, were found in sera from 10% of patients with TAO and
      16% of those with GH, but not from any patient with HT or normal subject. Similar
      patterns of connective tissue reactivity were also found in lacrimal gland,
      skeletal muscle, kidney and salivary gland. Antinuclear antibodies were detected
      in sera from 31% of patients with TAO, but from only 8% with HT, in no patient
      with GH and in only 3% of normal subjects. The most common pattern was a fine
      speckled fluorescence, found in 45% of sera, consistent with reactivity against
      the Sm antigen or nuclear RNP. The finding of a high prevalence of ANA and, less
      often, anti-connective tissue antibodies in patients with thyroid autoimmunity
      and ophthalmopathy, is consistent with Graves' disease being a "collagen-like
      disorder". The reason why inflammation and resulting tissue damage is limited to
      the thyroid, connective tissue of the skin and orbit, skeletal muscle and,
      possibly, the lacrimal gland, is unclear. One possibility is cross reaction of
      ANA with tissue specific membrane proteins in these sites. The extent of
      immunologic abnormalities, and the resulting clinical features, in patients with
      Graves' disease may reflect the severity of a putative defect in immune
      regulation.

PMID- 8750781
TI  - Autoimmune endocrine ophthalmopathy and retrobulbar antigens.
AB  - Endocrine Ophthalmopathy (EO) is based on autoimmune processes that lead to
      lymphocyte infiltration of the retrobulbar space. In this study, antigenic
      character of retrobulbar adipose, connective and muscle tissue as well as of
      cultured fibroblasts and myoblasts were examined. Samples were obtained from EO
      patients (n = 13, 8 fem., age 26-82 years, median 47 years) undergoing orbital
      decompression surgery. Retrobulbar and abdominal tissue from 7 controls (4 fem.,
      48 - 74 y) was investigated, too. Tissues were homogenized and the proteins were
      separated by SDS-PAGE according to molecular weight. In order to recover the
      separated proteins in soluble form, an electroelution technique was employed.
      Twenty-two separated soluble protein fractions were used as antigenic stimuli for
      autologous peripheral blood mononuclear cells (PBMC) separated by Ficoll gradient
      centrifugation. Subsequently, the proliferation of T cells was measured by [3H]
      thymidine uptake. A marked T cell response to protein fractions with molecular
      weight of 6 - 10 kD and 19 - 26 kD was detected (p < 0.001). These autoantigens
      were found readily reproducible in adipose tissue in 8 out of 9 EO patients,
      stimulation index (SI) to antigen 6 - 10 kD 29 +/- 4.6 (mean +/- SEM); 19 - 26 kD
      5 +/- 1.4 and in 3 out of 4 patients using retrobulbar eye muscle tissue (SI: 6 -
      10 kD 23 +/- 4.2; 19 - 26 kD 6 +/- 2). Using the proteins of cultured fibroblasts
      as antigen, the autologous PBMC from 2 out of 4 tested EO-patients also responded
      (SI: 7 +/- 2; 4 +/- 1.4). Testing cultured retrobulbar myoblasts of an EO
      patient, a response to the 19 - 26 kD antigen was found only (SI: 8.0). In
      response to retrobulbar or muscle proteins, PBMC of 2 controls showed also a
      higher proliferation rate (SI: 16 +/- 3.5; 13 +/- 2.8), whereas, a response to
      abdominal adipose or muscle proteins (4 controls) was never found. Thus, two
      orbital antigens reacting with autologous T cells could be demonstrated and may
      play an important role in the immunopathogenesis of EO. According to these
      findings, retrobulbar fibroblast antigens are most likely the main T cell
      targets.

PMID- 8750782
TI  - Elucidation of autoimmune disease mechanism based on testicular and ovarian
      autoimmune disease models.
AB  - This paper describes several selected models of autoimmune disease of the gonads.
      Based on these findings, I have reviewed current knowledge concerning the
      tolerance mechanisms that normally prevent gonadal autoimmunity, the potential
      events that can overcome such mechanism to trigger autoimmune diseases. In
      addition we also summarize the immunopathology of orchitis and our understanding
      of the mechanisms responsible for the immunopathology of the disease. Recent
      studies indicate that pathogenic T cells capable of eliciting autoimmune diseases
      in these organs develop in both the neonatal and adult thymuses and they persist
      in the normal peripheral immune system. However, the function of the pathogenic T
      cells in adult mice is normally under the control of regulatory T cells which
      maintain peripheral tolerance, and important phenotypic differences are being
      defined between these two functional CD4+ T cell subsets. When the clonal balance
      of these T cell subsets is tipped in favor of pathogenic T cells, autoimmune
      diseases of the gonads could ensue. Pathogenic T cells responsible for autoimmune
      oophoritis can be activated through stimulation by non-ovarian peptides that
      cross-react with self ovarian peptides at the level of the T cell receptor. This
      novel form of antigen mimicry depends in part on the sharing, between unrelated
      peptides, the few critical amino acids required for activation of pathogenic T
      cells. Antibodies can bind to the ovarian target antigens during the development
      of autoimmune orchitis and autoimmune oophoritis. However, the precise role of
      antibody in these autoimmune diseases has not been critically explored. In this
      study, I have described a novel mechanism of autoantibody induction. Immunization
      of female mice with a pure T cell peptide from ZP3 can lead to the production of
      antibodies against ZP3 domains outside the immunogenic ZP3 peptide. Evidently,
      endogenous antigens from normal and pathologic ovaries may reach peripheral
      immune tissues, and provide the antigenic stimulus to trigger an autoantibody
      response. This occurs at the same time when activation of ZP3 specific T cells is
      detected, and it is not simply a consequence of tissue injury. Importantly, the
      autoantibodies react with native antigenic determinants, and are potentially
      important in autoimmune disease pathogenesis.

PMID- 8750783
TI  - Perspectives on ovarian dysfunction and autoimmunity.
AB  - Recent research has documented the fact that a series of factors appear to play
      an important role during early phases of ovarian formation and function. Within
      the field of reproductive medicine some of the areas of future research will
      encompass genetical aspects, the influence of local regulatory growth factors,
      the role of innervation, the role of the resident immune cells, and the potential
      role of hCG. The influence of these factors can be studied in animal models.

PMID- 8750784
TI  - Progress in the immunointervention of type-1 diabetes mellitus.
AB  - Immunointervention studies with immunosuppressive drugs (Cyclosporin A,
      Azathioprine) in type-1 diabetic patients after clinical diagnosis demonstrated
      that improvement of beta-cell function is not sufficient and longlasting. Since
      80 - 90 % of the beta-cell mass are already destroyed at onset of type-1
      diabetes, intervention studies with nicotinamide and insulin (parenteral or oral)
      were undertaken in the early phase of type-1 diabetes. However, immunomodulation
      is restricted to familial cases of type-1 diabetes (only 10% of all cases), since
      prediction of the disease is not possible in the general population. It cannot be
      excluded that the described immunintervention may only postpone but not hinder
      the manifestation of type-1 diabetes. Interventions with tolerance induction by
      BCG or GAD are promising, but did not yet result in prevention of type-1 diabetes
      in humans. Finally, the most effective strategy would be primary prevention by
      vaccination or exposure prophylaxis. Should type-1 diabetes prove to be a disease
      that is provoked through molecular mimicry, i.e. an immunization by an
      environmental antigen, then strategies to avoid contact with the environmental
      trigger (f.e. cow's milk protein) or to vaccinate against it (f.e. Coxsackie
      virus protein P2-c) could be adopted. If all these interventions are not
      effective in the long term run, research should be concentrated on molecular
      approaches after improvement in gene transfer technology.

PMID- 8750785
TI  - Insulin-dependent diabetes mellitus and glycosaminoglycans.
AB  - The influence of diabetic nephropathy on urinary glycosaminoglycan distribution
      was assessed in 96 patients with insulin-dependent diabetes mellitus (IDDM, 49
      female, age: 16 - 64 yrs, median 35; duration of IDDM: 0 - 43 yrs, median 13 yrs)
      in comparison to 103 healthy controls (57 female, 17 - 82 yrs, median 40 yrs).
      Glycosaminoglycan concentration of 24 h urine samples was determined by means of
      precipitation with cethylpyridinium chloride and potassium acetate in ethanol
      followed by a colorimetric test with carbazole. A marked difference (p = 0.0008)
      in urinary glycosaminoglycan excretion between patients (19.0, 12.4, 35.6 mg/24
      h, median, 25th, 75th percentile) and controls (15.8, 10.4, 21.6 mg/24h) could be
      detected. In patients with insulin-dependent diabetes mellitus of longer
      duration, glycosaminoglycan excretion was increased (<10 years: 17.3, 10.8, 30.5
      mg/24 h; > 10 yrs: 23.3, 16.0, 39.1 mg/24 h; p = 0.03). Furthermore, diabetic
      patients with manifest nephropathy and retinopathy exhibited a significantly
      higher glycosaminoglycan excretion compared to patients without nephropathy
      (40.8, 23.3, 42.2 versus 18.2, 11.4, 31.0 mg/24 h, p = 0.005) or retinopathy
      (31.9, 16.6, 41.6 versus 17.6, 11.2, 26.7 mg/24 h, p = 0.009). Thus, the results
      of this study demonstrate a close relationship between diabetic nephropathy and
      the renal glycosaminoglycan excretion.

PMID- 8750786
TI  - Structural analysis of histamine N-methyltransferase gene.
AB  - A clone encoding a part of rat histamine N-tele-methyltransferase gene of 11 kb
      was isolated. The clone contained 4 exons, encoding from 191 to the 3' end of
      cDNA. The last exon was 692 bases long and specified more than half of the HMT
      cDNA. A comparison of the sequences of rat and human cDNAs shows that more than
      one-third of the human 3' untranslated region does not correspond to the rat
      counterpart, but a homology was found between this region of human cDNA and the
      3' franking region of the rat gene. It was found that an exon was interrupted at
      4 residues after a glycine residue, which putatively corresponds to the conserved
      residue among methyltransferases.

PMID- 8750787
TI  - De Novo synthesis and posttranslational processing of L-histidine decarboxylase
      in mice.
AB  - We purified L-histidine decarboxylase from mouse mastocytoma cells and cloned
      mouse HDC cDNA, and found that the primary translated product (74 kD) is
      posttranslationally processed in its C-terminal region to yield a native HDC
      subunit (53 kD). Recombinant 74-kD, but not 53-kD HDC species was present mainly
      in the particulate fraction of Sf9 cells. The particulate 74-kD recombinant HDC
      was cleaved by porcine pancreatic elastase, and a homodimer of a 53-kD subunit
      having the identical catalytic properties to those of native HDC was solubilized.
      The particulate HDC from mouse stomach was partially purified and it was
      solubilized by porcine pancreatic elastase to yield the 53-kD subunit of HDC. We
      identified endogenous proteolytic activity, which converts the particulate
      recombinant 74-kD HDC to the soluble 53-kD HDC in the supernatant of mouse
      stomach. In mastocytoma cells, we demonstrated that the induction of HDC activity
      and HDC mRNA synergistically occurred upon treatment with dexamethasone + TPA,
      and also with cAMP + Ca2+. On a genomic DNA cloning, we found that two
      upregulations occurred via the involvement of the regulatory elements binding to
      the sequences from -132 to -53 and -267 to -53, respectively.

PMID- 8750788
TI  - Expression and characterization of human recombinant parental and mature L
      histidine decarboxylases.
AB  - Human recombinant 74 kD parental (rHDC74) and 54 kD mature (rHDC54) histidine
      decarboxylases (HDCs) have been expressed in Sf9 cells and characterized. By
      immunoblot analysis, rHDC74 and rHDC54 were shown to be localized predominantly
      in the particulate and soluble fractions, respectively. rHDC74 exhibited
      histamine-synthesizing activity equivalent to that of rHDC54. An active
      particulate HDC was also detected in the pellets obtained from 10,000 and 100,000
      g centrifugation of a cell lysate from the human basophilic leukemia cell line,
      KU-812-F (14 and 18% of the total activity, respectively). By four purification
      steps, rHDC54 was purified to homogeneity, as judged by silver staining of the
      SDS-polyacrylamide gel. The purified rHDC54 was eluted as a monomer form from a
      Superdex-200 FPLC column. The molecular mass of the enzyme was found to be
      approximately 54 kD on SDS-poly-acrylamide electrophoresis in the absence of 2
      mercaptoethanol. Taken together, these results suggest that human HDC functions
      as both 74 and 54 kD forms having equivalent HDC activity, which are localized in
      the particulate and soluble fractions, respectively, and that the latter form
      exhibits its activity as a monomer form.

PMID- 8750789
TI  - The role of HMT (histamine N-methyltransferase) in airways: a review.
AB  - Histamine N-methyltransferase (HMT) expressed in the epithelial and endothelial
      cells of the airways is a principal enzyme degrading histamine in the body. This
      brief review summarizes the recent advances in molecular biology related to the
      pathophysiological role of HMT in regulating airway functions.

PMID- 8750790
TI  - Role of histamine produced by macrophages in mouse bone marrow.
AB  - Promyelocytic HL-60 cells differentiated into mature cells when they were
      cultured in the presence of dimaprit (10(-4) M), a histamine H2 agonist. An
      injection of Escherichia coli lipopolysaccharide increased the activity of
      histidine decarboxylase in bone marrow cells in C3H/HeN mice to a much greater
      extent than in C3H/HeJ mice, which are resistant to various effects of
      lipopolysaccharide. Histamine production increased concomitantly. In WBB6/F1
      (W/W(v)) mice, which are genetically deficient in mast cells, histidine
      decarboxylase activity increased more than in C3H/HeN mice. Pure (>99%
      nonspecific esterase, CD14 and Mac-1 positive) macrophage populations were
      obtained from long-term culture of the bone marrow cells (bone marrow-derived
      macrophages, BMDM). Culture of the cells in the presence of lipopolysaccharide
      caused a slight, but dose-dependent increase in histidine decarboxylase
      associated histamine synthesis. Granulocyte/macrophage colony-stimulating factor
      (rmGM-CSF) or interleukin 3 (rmIL-3) potently increased lipopolysaccharide
      induced histamine formation.

PMID- 8750791
TI  - Effect of repeated cold stress on mouse stomach histidine decarboxylase.
AB  - The effect of repeated cold stress (RCS) on both mRNA level and enzyme activity
      of stomach histidine decarboxylase (HDC) was studied in ddY mice. Following 1-day
      treatment of RCS, stomach HDC activity, but not its mRNA level, increased two
      fold. Following 3-day treatment of RCS, which is the essential period for the
      induction of hyperalgesia in mice, HDC mRNA level and enzyme activity increased
      in the stomach. After cessation of RCS treatment, HDC mRNA level decreased and
      reached the level of non-RCS treated mice, but HDC activity did not. The stomach
      from the 1-day RCS-treated mouse contained proteolytic activity, which converts
      the in vitro-translated 74 kD HDC species into the 53 kD HDC species. These data
      demonstrate that RCS-treated mouse stomach induces both the de novo synthesis of
      the 74 kD HDC species and its proteolytic cleavage to 53 kD HDC species.

PMID- 8750792
TI  - Role of histamine H3 receptor on hypoxia-reoxygenation-induced cardiac
      dysfunction in guinea pigs.
AB  - Hypoxia elicited a remarkable decrease in contractility and heart rate in
      isolated right atria from guinea pigs, a decrease which recovered partially
      during reoxygenation. Histamine content increased during hypoxia and decreased
      during reoxygenation. However, hypoxia induced a marked degranulation of mast
      cells. Pretreatment with alpha-methylhistamine (100-300 nM) recuperated control
      level contractility and heart rate, and prevented the hypoxia-reoxygenation
      induced leakage of creatine phosphokinase (CPK). On the other hand, pretreatment
      with thioperamide (100-300 nM) decreased contractility and heart rate dose
      dependently, and prevented recovery during reoxygenation. These data shows that
      cardiac histamine may play an important role in the protection against hypoxia
      reoxygenation injury through the H3 receptor.

PMID- 8750793
TI  - Allergic airway response and potassium channels: histamine release and airway
      inflammation.
AB  - The possible involvement of potassium (K) channels in allergic airway responses
      was examined in ovalbumin (OA)-sensitized guinea pigs. An ATP-sensitive K channel
      opener (BRL-38227) inhibited OA inhalation-induced bronchoconstriction and airway
      plasma leakage. BRL-38227 also had an inhibitory effect on exogenous histamine-
      and leukotriene-induced responses. In contrast, BRL-38227 did not affect OA
      induced histamine release from minced lung tissues. Therefore, the ATP-sensitive
      K channel opener inhibits allergic bronchoconstriction and plasma leakage as a
      result of its effect on airway smooth muscle and postcapillary venules. Apamin, a
      small conductance Ca2+ -activated K channel (PK,Ca) blocker, significantly
      inhibited both OA-induced tracheal contraction and histamine release from lung
      tissues, suggesting that this compound reduces allergic airway responses via a
      mast cell stabilizing effect. We conclude that ATP-sensitive K channel opening
      and small conductance PK,Ca closure may be beneficial for preventing allergic
      airway responses.

PMID- 8750794
TI  - The mechanism of histamine production in allergic inflammation.
AB  - In the air pouch-type allergic inflammation model in rats, histamine produced in
      the late phase plays a role in downregulation of leukocyte infiltration into the
      pouch fluid. In the pouch fluid, we found two kinds of histamine production
      increasing factor (HPIF); HPIF-1, which induces histamine production in bone
      marrow cells, and HPIF-2, which enhances the activity of HPIF-1. Isoelectric
      point and molecular weight of HPIF-1 and HPIF-2 were estimated to be pI 4-5 and
      25-40 kD, and pI 7-8 and about 100 kD, respectively. The histamine-producing
      ability of bone marrow cells increased after the antigen challenge, but that of
      peripheral leukocytes decreased markedly 8 h after the antigen challenge.
      Pharmacological analysis indicated that HPIF-1 induces histamine production
      through activation of protein kinase C and tyrosine kinase. Differentiation of
      bone marrow cells to histamine-producing cells by HPIF-1 was also indicated. From
      these observations, the histamine production in the late phase of allergic
      inflammation is suggested to be regulated by the production of HPIF-1,
      proliferation/differentiation of histamine-producing cells, and infiltration of
      histamine-producing cells in blood circulation into the inflammatory site.

PMID- 8750795
TI  - Effects of the histamine H3 agonist (R)-alpha-methylhistamine and the antagonist
      thioperamide in vitro on monoamine oxidase activity in the rat brain.
AB  - The effects of an H3 agonist, (R)-alpha-methylhistamine (alpha-MeHA), and an H3
      antagonist, thioperamide, on monoamine oxidase (MAO) activity in rat hypothalamus
      were studied in vitro. Thioperamide was more potent in inhibiting MAO-B than MAO
      A activity; MAO-B activity in rat hypothalamic homogenates was competitively
      inhibited by thioperamide with a Ki value of 175 micronM. From this in vitro
      experiment, the conversion of N-telemethylhistamine to N-tele
      methylimidazoleacetic acid may be inhibited by thioperamide, suggesting that
      thioperamide may affect the regulation of histamine metabolism within
      histaminergic neurons. In contrast with the results obtained with thioperamide,
      alpha-MeHA inhibited MAO-A more potently than MAO-B activity; the Ki values for
      MAO-A and -B of hypothalamic homogenates were estimated to be 1.1 and 3.3 mM,
      respectively. The weak inhibitory effect of alpha-MeHA for MAO-B does not seem to
      be a major cause of changes in N-tele-methylhistamine concentrations.

PMID- 8750796
TI  - Homeostatic maintenance regulated by hypothalamic neuronal histamine.
AB  - By manipulating hypothalamic neuronal histamine, its effects on brain functions
      related to homeostatic energy balance were assessed in non-obese normal and
      genetically obese Zucker rats. Feeding behavior was suppressed and drinking was
      accelerated by either activation of H1 receptors or inhibition of H3 receptors in
      the ventromedial hypothalamic nucleus (VMH) and the paraventricular nucleus, each
      of which is a satiety center. Energy deficiency in the brain, i.e., intraneuronal
      glucoprivation, produced satiation through histaminergic activation of VMH
      neurons. Such low energy intake in turn induced glycogenolysis in the astrocytes
      to protect energy deficit in the brain. Histamine neurons in the mesencephalic
      trigeminal nucleus (Me5) regulated masticatory functions, particularly eating
      speed, and those in the VMH controlled intake volume at meals. Hypothalamic
      histamine neurons were activated by high ambient temperature and also by
      interleukin-1beta, an endogenous pyrogen, through prostaglandin E2 to maintain
      homeostatic thermoregulation. Behavioral and metabolic abnormalities of obese
      Zuckers were the result of a defect in hypothalamic neuronal histamine.
      Abnormalities produced by depletion of neuronal histamine from the normal
      hypothalamus mimicked those of obese Zuckers. Grafting the lean fetal
      hypothalamus into the obese pups attenuated those abnormalities.

PMID- 8750797
TI  - Ameliorating effects of histidine on learning deficits in an elevated plus-maze
      test in mice and the contribution of cholinergic neuronal systems.
AB  - We investigated the effects of histidine on scopolamine-induced learning deficits
      in the elevated plus-maze test in mice. In this test, transfer latency, the time
      mice took to move from the open arm to the enclosed arm, was used as an index of
      learning and memory. Intraperitoneal administration of scopolamine (0.5 mg/kg)
      prolonged the transfer latency on day 2 as compared with that in the saline
      treated group. Histidine loading (500, 800 and 1600 mg/kg) reversed the
      prolongation of the transfer latency induced by scopolamine. This ameliorating
      effect of histidine was abolished by alpha-fluoromethylhistidine, an inhibitor of
      histidine decarboxylase, suggesting that histidine itself has no such
      ameliorating effect. Moreover, the ameliorating effect of histidine was
      antagonized by a histamine H1-receptor antagonist, pyrilamine, but not by
      zolantidine, a histamine H2-receptor antagonist. Thus, histamine, a
      decarboxylated product of histidine, elicited an ameliorating effect on
      scopolamine-induced learning deficit via histamine H1 receptors in mice. In the
      biochemical study, histidine significantly decreased acetylcholine (ACh) levels
      in the cerebral cortex and diencephalon of mice, and also significantly decreased
      them in the midbrain at a dose of 500 mg/kg. Histidine significantly increased
      and decreased levels of metabolites of noradrenaline and serotonin, respectively,
      in the brains of mice. Levels of dopamine and its metabolites were not very
      affected by histidine in the brains of mice. These findings clearly indicate that
      there is a close relationship between histaminergic and cholinergic system in the
      brain, and that histamine may play certain important roles in learning and
      memory.

PMID- 8750798
TI  - Positron emission tomographic study of central histamine H1-receptor occupancy in
      human subjects treated with epinastine, a second-generation antihistamine.
AB  - Histamine H1-receptor occupancy in the human brain was measured in healthy young
      volunteers by positron emission tomography (PET) using [11C]doxepin. d
      Chlorpheniramine, a selective and classical antihistamine, occupied 76.8 +/- 4.2%
      of the averaged values of available histamine H1 receptors in the frontal cortex
      after its administration in a single oral dose of 2 mg. Epinastine, a non
      sedative antihistamine, occupied 13.2 +/- 18.5% of the available H1 receptors in
      the human frontal cortex after its administration in a single oral dose of 20 mg.
      There was significant correlation between H1 receptor occupancy by epinastine and
      its plasma concentration in each subject. PET data on the human brain were
      essentially compatible with those on H1-receptor occupancy in the guinea pig
      brain as determined by an in vivo binding technique, although for the same H1
      receptor occupancy, the dose was less in humans than in guinea pigs. Our PET
      studies demonstrated that receptor occupancy by a second-generation H1
      antagonist, epinastine, was less than 20% of the total H1 receptors, and that the
      low receptor occupancy was closely related to the low incidence of central side
      effects.

PMID- 8750799
TI  - AQ-0145, a newly developed histamine H3 antagonist, decreased seizure
      susceptibility of electrically induced convulsions in mice.
AB  - We studied the effect of AQ-0145, a newly developed histamine H3-receptor
      antagonist, on electrically induced convulsions in mice. AQ-0145 significantly
      decreased the durations of each convulsive phase. The anticonvulsant effect of AQ
      0145 was antagonized by mepyramine (pyrilamine) and ketotifen, centrally acting
      histamine H1-receptor antagonists. Thus, the blockade by histamine H1 antagonists
      of the AQ-0145-induced decrease in seizure susceptibility indicated that
      histamine released by AQ-0145 from the histaminergic nerve terminals interacts
      with the histamine H1 receptors of postsynaptic neurons. These findings fully
      support the hypothesis that the central histaminergic neuronal system is involved
      in the inhibition of seizures. It is suggested that the neuropharmacological data
      on histamine H3 ligands may provide clinical candidates for the CNS disorders in
      which histamine plays important roles in mental and behavioral functions. In this
      study, it was suggested that AQ-0145 was a new clinical candidate of H3 ligands.

PMID- 8750800
TI  - Childhood brucellosis in north-western Greece: a retrospective analysis.
AB  - Fifty-two cases of childhood brucellosis which occurred in north-western Greece
      during the 15-year period 1979-1993, are reviewed. It is believed that they
      represent very closely the total incidence of the disease in the region which has
      a population of 100,000 children aged 0-14 years old. Brucellosis-affected
      children were almost exclusively from goat- or shepherd families and of both
      sexes and all age groups. A broad spectrum of clinical manifestations ranging
      from malaise only to brain abscess was observed. Fever and arthralgia were the
      most common manifestations followed by malaise, myalgia, sweating, rash, cough,
      and gastro-intestinal, cardiac and CNS involvement. Splenomegaly was found more
      often than hepatomegaly and lymphadenopathy. Laboratory findings included
      anaemia, leukopenia, neutropenia, lymphocytopenia, monocytosis, eosinophilia,
      thrombocytopenia and pancytopenia. Leukocytosis and lymphocytosis were extremely
      rare and ESR and serum C-reactive protein levels were mildly elevated. All
      patients had positive Rose Bengal slide agglutination tests and standard tube
      agglutination titres of 1:160 or more. When performed, blood culture was often
      diagnostic. The children were treated with streptomycin for 2 weeks plus either
      tetracyclines or trimethoprim-sulphamethoxazole for 3 weeks. Treatment was well
      tolerated. Relapse was observed in one case. CONCLUSION: Brucellosis nowadays
      affects children in an occupational pattern. As symptoms, signs and first-line
      laboratory findings are not characteristic, agglutination tests and blood culture
      should be performed in any child with prolonged fever. Treatment is effective,
      but prevention of the disease by animal testing and education of high risk
      families is indicated.

PMID- 8750801
TI  - Familial idiopathic atrial fibrillation with bradyarrhythmia.
AB  - A 10-year-old boy is reported who presented with idiopathic atrial fibrillation
      and bradyarrhythmia. After history of intrauterine and postnatal bradycardia,
      atrial fibrillation was first documented electrocardiographically at 16 months of
      age. An underlying structural heart disease was not evident. At the age of 10
      years, implantation of a permanent ventricular demand pacemaker was indicated
      after syncope due to severe bradyarrhythmia. The family history revealed five
      persons of four generations with bradyarrhythmias. Idiopathic atrial fibrillation
      known since childhood was documented in three close relatives. A high grade AV
      block resulting in bradyarrhythmias and the occurrence of ST-T-changes in
      precordial leads could be demonstrated in all affected family members suggesting
      a diffuse general conduction abnormality in these patients. In this family,
      idiopathic atrial fibrillation seems to be transmitted as an autosomal dominant
      trait. CONCLUSION: Atrial fibrillation without underlying heart disease is
      extremely rare in children. Careful electrocardiographic follow-up of these
      patients and the evaluation of ECG recordings of all family members is
      recommended.

PMID- 8750802
TI  - Heparin as a cause of thrombus progression. Heparin-associated thrombocytopenia
      is an important differential diagnosis in paediatric patients even with normal
      platelet counts.
AB  - A 15-year-old boy developed deep vein thrombosis of the right leg 9 days after
      appendectomy. In spite of three courses of thrombolysis with streptokinase and
      effective heparinization the thrombosis progressed with additional occlusion of
      the left iliac vein. Although platelet counts were constantly normal, heparin
      associated thrombocytopenia was suspected as the cause of the new venous
      occlusions. This diagnosis was confirmed by detecting heparin-associated
      antibodies with the heparin-induced platelet activation test. Therapy was
      instituted replacing heparin by the low molecular weight heparinoid Orgaran.
      Bilateral recanalization occurred within 6 days. CONCLUSION: Heparin-associated
      thrombocytopenia must be considered if thrombosis occurs or progresses despite
      effective heparinization even in the absence of thrombocytopenia.

PMID- 8750803
TI  - Treatment of osteopenia in children with insulin-dependent diabetes mellitus: the
      effect of 1 alpha-hydroxyvitamin D3.
AB  - Twelve children (8 boys and 4 girls) with insulin-dependent diabetes mellitus
      (IDDM), aged 9-15 years, received 1 alpha-hydroxyvitamin D3 (1 alpha-OHD3) in a
      dose of 0.05 microgram/kg per day for 1 year. Duration of disease varied between
      2.8 and 9 years. Bone density was determined in the distal third of forearm using
      single photon absorptiometry, and was expressed as standard scores (+/- SD) with
      respect to sex- and age-matched controls. Bone density measurements and
      ultrasound studies of the kidneys were performed at 0, 6 and 12 months. Serum
      calcium, ionized calcium, phosphorus, magnesium, creatinine, alkaline
      phosphatase, glycosylated haemoglobin in morning blood samples and urinary Ca, P,
      Mg, and hydroxyproline were regularly determined. One patient was excluded from
      the study because of hypercalciuria and one because of lack of compliance. Bone
      density increased significantly after 6 and 12 months of 1 alpha-OHD3
      administration (P = 0.015, P < 0.001 respectively). None of the biochemical
      parameters changed significantly. CONCLUSION: Osteopenia is not uncommon in
      children and adolescents with IDDM. In 10 children with IDDM and osteopenia the
      administration of 1 alpha-OHD3 for 1 year corrected bone loss.

PMID- 8750804
TI  - The Rapunzel syndrome (trichobezoar) causing gastric perforation in a child: a
      case report.
AB  - The Rapunzel syndrome (RS), is a rare form of gastric trichobezoar extending
      throughout the bowel. We report on a patient with RS causing gastric perforation
      and discuss the aetiology, pathogenesis, diagnosis and treatment of this unusual
      syndrome. RS is found characteristically in girls with varying gastro-intestinal
      symptoms. The recommended treatment for large or complicated trichobezoars is
      surgery. Psychiatric follow up is essential to diminish the frequency of
      recurrence. CONCLUSION: Symptoms of trichobezoars are nonspecific and may mimic
      those of other pathological gastro-intestinal conditions. Early diagnosis and
      treatment of this condition is of prime importance and may avoid later fatal
      complications.

PMID- 8750805
TI  - Purpura fulminans in severe congenital protein C deficiency: monitoring of
      treatment with protein C concentrate.
AB  - This report describes the successful use of protein C concentrate to treat severe
      purpura fulminans in a homozygous protein C-deficient infant for 8 months until
      oral anticoagulation was initiated. While fresh frozen plasma was previously used
      in such cases to replace protein C in the acute phase, the availability of a
      monoclonal antibody purified protein C concentrate now allows specific
      replacement of protein C, avoiding problems of fluid overload. An occlusive
      hydrocolloid bandage proved to be effective in local treatment of skin lesions. D
      dimer, fibrin monomer, thrombin-antithrombin complex and prothrombin fragment 1 +
      2 were useful markers in monitoring and optimizing protein C replacement therapy.
      CONCLUSION: Diagnosis of protein C deficiency should be considered in a newborn
      with purpura fulminans. Early diagnosis and adequate replacement therapy is life
      saving. Today, administration of protein C is the acute as well as long-term
      therapy of choice.

PMID- 8750806
TI  - Recurrent bacterial meningitis.
AB  - To characterize recurrent bacterial meningitis in children, we reviewed the
      charts of all patients treated for more than one episode of bacterial meningitis
      at the Wurzburg University Children's Hospital from 1980 to June 1995. Twenty
      five children suffered 2-13 episodes of bacterial meningitis. Most patients were
      referred from other hospitals to our paediatric neurosurgical service. No
      immunodeficiency was found. In all patients, the cause of recurrent meningitis
      was an anatomical lesion with 13 intracranial defects including encephaloceles,
      skull fractures, Mondini dysplasias, neurenteric cyst, fibrous dysplasia,
      persistent craniopharyngeal duct, and 12 lumboscral defects with a dermoid cyst
      within the lumbosacral spine. A first episode of meningitis at school age did not
      exclude a congenital defect. In total, 84 episodes of meningitis were treated, a
      pathogen was isolated in 77%. The most common pathogen was Streptococcus
      pneumoniae, followed by Escherichia coli, Staphylococci and others. The pathogen
      isolated often gave a clue to the location of the defect. Personal history was
      often unrewarding and in some cases the search for the anatomical lesion required
      repeated imaging and explorative surgery. In 24 of 25 cases, final treatment of
      recurrent meningitis was by surgical intervention. CONCLUSION: In recurrent
      bacterial meningitis, excessive diagnostic and therapeutic procedures are
      indicated. An anatomical defect is a very probable cause.

PMID- 8750807
TI  - Propionylcarnitine excretion is not affected by metronidazole administration to
      patients with disorders of propionate metabolism.
AB  - Propionylcarnitine (PC) excretion has been measured during a clinical trial of
      metronidazole therapy in two patients with propionic acidaemia and two patients
      with methylmalonic aciduria. All patients were in good metabolic control and were
      receiving L-carnitine. While total propionate excretion was reduced by up to 40%
      in all four patients during metronidazole therapy, the excretion of
      propionylcarnitine remained largely unchanged. PC comprised up to 80% of total
      propionate excretion in patients with propionic acidaemia. CONCLUSION: These
      results suggest an extra-hepatic source and/or differing compartmentation for PC
      formation from those for the production of other metabolites of propionyl-CoA.

PMID- 8750808
TI  - Rotavirus infection and bradycardia-apnoea-episodes in the neonate.
AB  - Rotavirus (RV), a common cause of infectious enteritis in young children
      including neonates, has not been associated with central nervous symptoms in
      standard textbooks. However, involvement of the CNS has been reported recently in
      case reports and small series. From 786 neonatal admissions in 1991 we
      retrospectively analysed the records of 215 inpatient neonates (68 preterm and
      147 term infants) who developed diarrhoea during their stay on the neonatal ward
      and in whom stools were investigated for RV antigen by ELISA. All 215 neonates
      were continuously monitored for bradycardia-apnoea-episodes (BAE) at least 2 days
      before and during the entire diarrhoeal period. In neonates with RV antigen in
      stools (n = 114) we found a higher incidence of BAE compared to neonates with RV
      negative stools (33% vs 8%, P < 0.001 for bradycardia; 7% vs 0%, P < 0.05 for
      apnoea). Furthermore, bradycardia episodes of RV positive neonates were more
      often followed by cyanosis (11 vs 0%, P < 0.05) and intervention was more often
      necessary (31 vs 14%, P < 0.05) than in the RV negative neonates. CONCLUSION: RV
      infection was associated with a high incidence of BAE in neonates with diarrhoea
      during the acute phase of disease suggesting CNS involvement.

PMID- 8750809
TI  - Complement anaphylatoxin C3a and C5a formation in premature children with
      respiratory distress.
AB  - Premature children (n = 25) with respiratory distress (RD) were studied regarding
      complement activation and formation of the anaphylatoxins C3a and C5a. Blood
      samples were drawn on admission to the paediatric intensive care unit. In 18 of
      the patients RD was accompanied by other perinatal complications like
      pneumothorax or intracerebral haemorrhages. Seven of the premature children had
      RD without such complications. Preterm children with RD and with peri- and
      postnatal complications such as pneumothorax or intracerebral haemorrhage had
      increased concentrations in plasma of the anaphylatoxins C3a and C5a compared
      with preterm children with RD without these complications. There was a positive
      correlation between the plasma C3a and C5a concentrations in the preterm
      children. CONCLUSION: The present study indicates that isolated RD will appear
      without signs of complement activation and that complications like pneumothorax
      or intracerebral haemorrhages are associated with release of the anaphylatoxins
      C3a and C5a.

PMID- 8750810
TI  - Hyponatraemia and cerebral convulsion due to short term DDAVP therapy for control
      of enuresis nocturna.
AB  - Desmopressin (DDAVP) is frequently used in the treatment of primary isolated
      enuresis nocturna if other approaches have failed. We report a further case of
      hyponatraemia and cerebral convulsion due to water intoxication after intranasal
      DDAVP application by a 6 year-old boy with enuresis. CONCLUSION: Although adverse
      reactions in DDAVP (e.g. hyponatraemia) are rare, it should not be considered as
      the first choice treatment of enuresis nocturna and only be used with caution.

PMID- 8750811
TI  - Alport syndrome: clinical experience with 21 paediatric patients.
AB  - The clinical, histological and genetic features of Alport syndrome are presented
      and illustrated by our experience with 21 paediatric patients seen over the last
      22 years. From the 15 boys, 7 went into end-stage renal failure before the age of
      20 years. In the 6 girls, the symptomatology was limited to permanent haematuria
      and mild proteinuria. CONCLUSION: Alport syndrome should be included in the
      differential diagnosis of permanent haematuria even in the absence of any
      suggestive familial antecedent.

PMID- 8750812
TI  - Severe hypertension: an unusual presentation of Guillain-Barre syndrome in a
      child with brucellosis.
AB  - A 9-year-old girl suffered from protracted paroxysms of severe hypertension
      before she developed classical signs of Guillain-Barre syndrome. Significant
      brucella antibody titres were found in the serum and CSF. Complete recovery was
      observed after appropriate therapy. CONCLUSION: Brucella organisms should be
      sought as a possible aetiological agent of Guillain-Barre syndrome in patients
      living in or coming from endemic countries.

PMID- 8750813
TI  - Sleep disordered breathing: effects of adenotonsillectomy on behaviour and
      psychological functioning.
AB  - Children on the adenotonsillectomy waiting list aged 6 years or more were
      screened by questionnaire and overnight sleep monitoring to identify 12 with a
      moderate sleep and breathing disorder (SBD) group. They were matched by age and
      sex with 11 children who had a similar history of snoring and sleep disturbance
      but without an obvious sleep and breathing problem when monitored (snorer group)
      and also with a group of ten children most of whom were refered for an unrelated
      surgical procedure (control group). All children were studied before and 3-6
      months after surgery. Pre-operatively the SBD and snorer groups both had
      significantly more restless sleep than the control group. The SBD group also had
      significantly more (> 4%) dips in oxygen saturation than the other two groups.
      After surgery there were no longer any significant differences between the three
      groups. After adenotonsillectomy the SBD group showed a significant reduction in
      aggression, inattention and hyperactivity on the parent Conners scale, and an
      improvement in vigilance on the Continuous Performance Test. The snorer group
      also improved showing less hyperactive behaviour than pre-operatively and better
      vigilance. The control groups's behaviour and performance did not change
      significantly. There were no significant changes in the performance of the
      Matching Familiar Figures Test in any of the groups. CONCLUSION: Relief of mild
      to moderate sleep and breathing disorders in children is associated with improved
      behaviour and functioning. We confirm previous work which suggests that the
      relation between sleep disordered breathing and daytime problems in children is a
      causal one.

PMID- 8750814
TI  - Case of the month.

PMID- 8750815
TI  - Jugular phlebectasia in children.

PMID- 8750816
TI  - Unusual neurological presentation of dipylidiasis in a child.

PMID- 8750817
TI  - Use of crystalloid or colloid for partial exchange transfusion in polycythemic
      newborns.

PMID- 8750818
TI  - Bilateral pleural and pericardial effusions complicating insertion of a central
      venous catheter.

PMID- 8750819
TI  - Granulocyte-marophage colony-stimulating factor in human milk.

PMID- 8750820
TI  - Low molecular weight heparin for anticoagulation during haemodialysis in children
      -a preliminary study.

PMID- 8750821
TI  - Cloning and characterization of the rat GALR1 galanin receptor from Rin14B
      insulinoma cells.
AB  - Galanin is a ubiquitous neuropeptide that regulates a wide array of physiological
      processes via interaction with specific G protein-coupled receptors. A rat
      galanin receptor cDNA was cloned from the Rin14B insulinoma cell line. The
      isolated cDNA encodes a 346 amino acid G protein-coupled receptor that is 92%
      identical to the recently reported human GALR1 galanin receptor. [125I]Galanin
      binds with high affinity to two receptor states in COS1 cell membranes containing
      the rat GALR1 receptor, consistent with coupling of the receptor to a G protein
      in these membranes. N-terminal galanin fragments and the putative galanin
      receptor antagonists galantide, C7, M35 and M40 bind with high affinity to the
      rat GALR1 receptor. In contrast, C-terminal galanin fragments do not bind to this
      receptor. Galanin inhibits basal and forskolin-stimulated cAMP formation in CHO
      cells expressing the rat GALR1 receptor via a pertussis toxin-sensitive G
      protein. The GALR1 receptor is expressed in rat spinal cord, small intestine,
      Rin14B insulinoma cells and several brain regions, particularly ventral
      hippocampus, amygdala, supraoptic nucleus, hypothalamus, thalamus, lateral
      parabrachial nucleus and locus coeruleus. Cloning of the rat GALR1 galanin
      receptor cDNA will permit many new experimental strategies to be applied to
      studies of the structure and function of galanin receptors.

PMID- 8750822
TI  - Adrenalectomy reduces FGF-1 and FGF-2 gene expression in specific rat brain
      regions and differently affects their induction by seizures.
AB  - We have previously reported that limbic seizures regulate the gene expression of
      fibroblast growth factor-2 (basic, FGF-2) according to a specific spatio-temporal
      pattern. In the present paper we have investigated the role of adrenal hormones
      on seizure-induced elevation of fibroblast growth factor-1 (acidic, FGF-1) and
      FGF-2 gene expression. Adrenalectomy reduces FGF-2 mRNA expression in specific
      brain regions, such as frontal cortex, hippocampus and striatum, whereas FGF-1
      mRNA levels were decreased only in the frontal cortex. The injection of kainic
      acid in adrenalectomized rats produced a widespread increase of FGF-2 mRNA with a
      pattern similar to sham animals as indicated by in situ hybridization. In
      contrast, although kainate-induced elevation of FGF-1 mRNA in the hippocampus was
      not influenced by adrenalectomy, its induction in frontal cortex was prevented by
      this surgery procedure. Taken together, these data indicate that adrenal hormones
      play a role in the regulation of the gene expression for fibroblast growth
      factors, but different mechanisms are operative in their induction following
      seizure activity.

PMID- 8750823
TI  - Spontaneous and evoked glutamate signalling influences Fos-lacZ expression and
      pyramidal cell death in hippocampal slice cultures from transgenic rats.
AB  - Previously, we established that a spatially and temporally predictable pattern of
      spontaneous cell death occurs in pyramidal hippocampal neurons maintained in
      organotypic slice cultures. We have begun to examine the signalling events that
      may be relevant to this process by analyzing the expression of cellular immediate
      early genes (cIEGs). In the present studies, organotypic hippocampal cultures
      were generated from transgenic rats that carry a fos-lacZ fusion gene. beta
      Galactosidase activity in these rats accurately recapitulates Fos expression. An
      association was observed between cell death, as determined by propidium iodide
      (PI) staining, and Fos-lacZ expression. There was a consistent rise in beta
      galactosidase activity in vulnerable regions 1-2 days before the peak of
      spontaneous neuronal death. Long-term treatment with TTX, CNQX, or D,L-APV
      inhibited the spontaneous neuronal death as well as Fos-lacZ expression.
      Furthermore, Fos-lacZ induction and cell death could be evoked by removal of
      these receptor antagonists or by application of the excitotoxin, kainic acid. The
      association between cIEG expression and cell death, shown here and by others,
      suggests that these genes contribute to regulatory events involved with cell
      death and/or protection.

PMID- 8750824
TI  - Primary astroglial cultures derived from several rat brain regions differentially
      express mu, delta and kappa opioid receptor mRNA.
AB  - The existence of opioid receptors within glial cell membranes has been proposed
      by several laboratories based on biochemical and radioligand binding data. The
      recent cloning of the mu, delta and kappa receptors has enabled us to directly
      examine the issue of opioid receptor expression in rat brain astroglia by using
      solution hybridization/ribonuclease protection assays to analyze the total RNA
      obtained from primary cultures of cortical, striatal, cerebellar, hippocampal and
      hypothalamic astrocytes. The results indicate that all five glial cultures
      expressed mu, delta and kappa receptor mRNA. The rank order of receptor mRNA
      abundance, expressed collectively across all five cultures, was determined to be
      delta > or = kappa >> mu. An analysis of the glial distribution profile for each
      receptor type revealed that mu receptor mRNA levels were the most abundantly
      expressed in cortical cultures, while the greatest levels of delta receptor mRNA
      were found in the cortical and hypothalamic cultures, and significant kappa
      receptor mRNA levels were produced by the cortical, hypothalamic and cerebellar
      cultures. Furthermore, the five glial cultures each expressed different levels of
      total opioid receptor (mu + delta + kappa) mRNA. The rank order of total opioid
      receptor mRNA expression across different astroglial cultures was found to be
      cortex > hypothalamus > cerebellum = hippocampus > striatum. An analysis of the
      relative expression profiles for mu, delta and kappa receptor mRNA within each
      culture revealed that all cultures manifested relatively high levels of delta and
      kappa receptor mRNA, but relatively low levels of mu receptor mRNA. Generally,
      cortical, hippocampal and hypothalamic cultures were characterized by comparable
      levels of delta and kappa receptor mRNA, and little, if any, mu receptor mRNA.
      However, striatal cultures were characterized by a high level of delta receptor
      mRNA which was approximately twice and four times that of the kappa and mu
      receptor mRNA, respectively. In contrast, cerebellar cultures expressed
      predominantly kappa receptor mRNA at a level which was almost twice that of the
      delta receptor mRNA, and expressed very little mu receptor mRNA. These data show
      that primary astroglial cultures not only express mu, delta and kappa receptor
      mRNAs, but they do so in a manner dependent upon receptor type and brain region.
      This suggests a regional heterogeneity of astrocytes with respect to opioid
      receptor expression, a characteristic previously described only for neurons.
      Furthermore, it suggests the existence of an additional anatomical component in
      CNS opioid systems.

PMID- 8750825
TI  - Increased expression of synapsin I mRNA in defined areas of the rat central
      nervous system following chronic morphine treatment.
AB  - Chronic opiate administration leads to a selective regulation of several cellular
      proteins and mRNAs. This phenomenon has been viewed as a compensatory mechanism
      to the opiate signaling leading to the development of opiate addiction. In this
      study, in situ hybridization histochemistry experiments were employed to
      investigate the effect of chronic morphine treatment on synapsin I gene
      expression. We show here for the first time that prolonged morphine exposure
      causes a selective increase in the mRNA levels of synapsin I in several brain
      regions which are considered to be important for opiate action. Quantitative
      analysis of the signals, obtained by hybridization of digoxigenin-labeled
      antisense RNA probe, revealed a 5.8- and 7-fold increase of synapsin I mRNA
      levels in the locus coeruleus and the amygdala of morphine-treated rats,
      respectively, as compared with control untreated rats. Increased expression of
      synapsin I mRNA was also observed in the spinal cord of morphine-treated rats (by
      3.8-fold). Since opiates were shown to attenuate neurotransmitter release and
      reduce synapsin I phosphorylation, it is suggested that the increase in synapsin
      I levels would lead to the requirement of higher amounts of opiate agonists to
      obtain the opiate physiological effects. These results suggest that the increases
      in mRNA levels of synapsin I in these specific areas can be part of the molecular
      mechanism(s) underlying opiate tolerance and withdrawal.

PMID- 8750826
TI  - Expression of inducible cAMP early repressor (ICER) in hypothalamic magnocellular
      neurons.
AB  - Cyclic AMP-responsive genes are regulated both positively and negatively by a
      number of constitutively expressed nuclear proteins. These proteins bind to cAMP
      responsive DNA elements in their target genes and they are activated by protein
      kinase A-mediated phosphorylation. The cAMP response element modulator gene
      encodes for several constitutively expressed products. However, a second intronic
      promoter within the gene is inducible and produces another negatively acting
      transcription factor, inducible cAMP early repressor (ICER). ICER shows a diurnal
      pattern of expression in the pineal gland, but to date it has not been noted
      elsewhere in the brain. Here we show expression of ICER mRNA in hypothalamic
      magnocellular neurons following osmotic stimulation over a time course consistent
      with a modulatory effect on the expression of other immediate-early genes, such
      as c-fos. However, since ICER was not present in magnocellular neurons during
      parturition, its presence is not a prerequisite for the transient expression of c
      fos.

PMID- 8750827
TI  - Na+ channel beta 1 subunit mRNA expression in developing rat central nervous
      system.
AB  - The sodium channel beta 1 subunit (Na beta 1) is a component of the rat brain
      voltage-dependent sodium channel. We have used nonradioactive in situ
      hybridization cytochemical techniques to demonstrate that transcript levels of Na
      beta 1 are differentially upregulated during postnatal development of several CNS
      regions, with selective labeling of specific neuronal populations. In the
      hippocampus, labeling of the pyramidal cell layer (particularly in the CA3
      region) and dentate granule cells was initially observed at postnatal day 2 (P2)
      and P10, respectively, and became progressively more intense with maturation.
      Labeled cells were first observed in the hilus at P10. In the developing
      cerebellum, transient labeling was observed in the external granule cell layer
      beginning at P1 while label increased in the internal granule cell layer up to
      P21. Purkinje cells showed significant label beginning at P4 and increasing up to
      P21. Weak signal was seen in neurons of deep nuclei at P1 and increased up to
      P21. Na beta 1 labeling in the spinal cord was first observed in the ventral horn
      at P2, and the intensity of labeling in these large motoneurons gradually
      increased. In addition, there was a ventral-dorsal gradient in this region, with
      label appearing subsequently in neurons of Rexed laminae IX, VII and VIII, and in
      the dorsal horn (Rexed laminae I-VI). In these regions, the labeling reached a
      plateau within the first 2-3 weeks after birth and persisted into the adult rat.
      The time course and regional heterogeneity of Na beta 1 expression are consistent
      with the hypothesis that the expression of mature Na+ channels, including Na beta
      1, contributes to the development of circuitry that supports complex patterns of
      electrogenesis.

PMID- 8750828
TI  - Identification of a negative regulatory element in the 5'-flanking region of the
      human dopamine beta-hydroxylase gene.
AB  - Transient transfection experiments indicate that a 5'-flanking upstream domain,
      residing between -437 and -262 bp of the human dopamine beta-hydroxylase (DBH)
      gene, has a cell type-specific silencer function. This domain contains a putative
      silencer motif (which we designate DBH negative regulatory element, DNRE),
      showing sequence homology with the neural-restrictive silencer element (NRSE or
      RE-1) recently characterized in type II sodium channel, SCG10 and synapsin I
      genes. When the DNRE was placed at the proximal 262 bp of the homologous (DBH)
      promoter, it exhibited strong silencer activity both in DBH-expressing SK-N
      BE(2)C as well as in DBH-nonexpressing HeLa cells. In addition, the DNRE also
      exhibited modest silencer activity upon a heterologous tk (herpes simplex virus
      thymidine kinase) promoter in both cell lines. Electrophoretic mobility shift
      assay demonstrated that nuclear extracts from both SK-N-BE(2)C and HeLa cells
      contain protein(s) that specifically bind to the DNRE. Formation of this
      DNRE/protein complex was specifically inhibited by an excess of unlabeled DNRE or
      NRSE. Finally, a similar sequence motif residing in the corresponding upstream
      area of the rat DBH gene also had a negative regulatory function, indicating that
      the silencer function of the DNRE is conserved in human and rat DBH genes.

PMID- 8750829
TI  - Activation of heat shock factor 1 in rat brain during cerebral ischemia or after
      heat shock.
AB  - Recently, many studies have demonstrated the induction of stress proteins in the
      mammalian nervous system under various pathological conditions. These altered
      genetic programs may function to protect individual cells against stressful
      conditions. However, little is known about the molecular mechanisms regulating
      these stress responses in animals. We report here the activation of a heat shock
      factor (HSF) in the rat brain during cerebral ischemia or after heat shock. Gel
      mobility shift assays revealed an increase in DNA binding activity to the heat
      shock element (HSE) during the early phases of ischemia. Supershift experiments
      using specific antisera against HSF1 and HSF2 showed that the ischemia-induced
      HSE-binding activity was mainly due to HSF1. In the heat-shocked brain, HSF1 was
      also activated, and the HSE-binding activity was higher in the cerebellum than in
      the cerebral cortex or hippocampus; Western blot analysis also showed that HSF1
      was more abundant in the cerebellum than in the other two brain regions. Our
      results indicate that heat shock gene transcription is regulated by the
      activation of HSF1 in both cerebral ischemia and heat shock, and that different
      brain regions display differential sensitivities in their stress response. The
      cellular signals for heat shock gene transcription under in vivo pathological
      conditions will also be discussed.

PMID- 8750830
TI  - The expression of neuronal voltage-dependent calcium channels in human
      cerebellum.
AB  - Little is known about the comparative distribution of voltage-dependent calcium
      channel subtypes in normal human brain. Previous studies in experimental animals
      have predominantly focused on the regional expression of single alpha 1 genes. We
      describe the preparation of riboprobes and antisera specific for human alpha 1A,
      alpha 1B and alpha 1E subunits and their application in comprehensive mapping
      studies of the human cerebellum. Within the cerebellar cortex, these pore forming
      proteins were found to have differential localisations when examined in adjacent
      sections. The alpha 1A and alpha 1B subunits broadly colocalised and were both
      present, though at apparently different levels, in the molecular, Purkinje and
      granule cell layers whilst alpha 1E was predominantly expressed in Purkinje
      cells. In the dentate nucleus, an area which has received little attention in
      previous studies, alpha 1A was highly expressed in regions in which Purkinje cell
      nerve terminals form synapses with deep cerebellar neurones.

PMID- 8750831
TI  - Oligodendrocyte-reactive O1, O4, and HNK-1 monoclonal antibodies are encoded by
      germline immunoglobulin genes.
AB  - Natural or physiologic autoantibodies are present normally in serum, are
      polyreactive, are frequently of the IgM subtype, and are encoded by unmutated
      germline genes. We tested whether the oligodendrocyte-reactive O1, O4, A2B5, and
      HNK-1 IgM kappa monoclonal antibodies are natural autoantibodies by sequencing
      immunoglobulin (Ig) cDNAs and comparing these with published germline sequences.
      O1 VH was identical with unrearranged VH segment transcript A1 and A4. O4 VH had
      three and HNK-1 VH had six nucleotide differences from germline VH101 in the VH
      coding region. The D segment of O1 was derived from germline SP2 gene family. The
      D segments of O4 and HNK-1 were derived from DFL16 gene family. O4 JH and HNK-1
      JH were encoded by unmutated germline JH4, whereas O1 JH was encoded by germline
      JH1 with one silent nucleotide change. O1 and O4 light chains were identical with
      myeloma MOPC21 except for one silent nucleotide change. HNK-1 V kappa was
      identical with germline V kappa 41 except for two silent nucleotide changes. O1 J
      kappa, O4 J kappa and HNK J kappa were encoded by unmutated germline J kappa 2.
      In contrast, A2B5 VH showed seven nucleotide differences from germline V1,
      whereas no germline sequence encoding A2B5 V kappa was identified. O1 and O4, but
      not A2B5 were polyreactive against multiple antigens by direct ELISA. Therefore,
      O1, O4 and HNK-1 Igs are encoded by germline genes, and have the genotype and
      phenotype of natural autoantibodies.

PMID- 8750833
TI  - Expression of the neuropeptide Y Y1 receptor in human embryonic kidney 293 cells:
      ligand binding characteristics, in situ hybridization and receptor
      autoradiography.
AB  - The human neuropeptide Y Y1 receptor cDNA was transfected into human embryonic
      kidney 293 (HEK 293) cells and used to determine the selectivity of newly
      developed Y1 and Y2 radioligands in a model which expresses a single NPY receptor
      subtype. The Y1 receptor probe, [125I][Leu31,Pro34]PYY, binds with high afinity
      (KD of 0.4-0.6 nM) to Y1-transfected HEK 293 cells whereas the Y2 radioligand,
      [125I]PPY3-36 failed to demonstrate any significant labelling. Only non-selective
      (PYY) or selective Y1 receptor agonists behaved as potent competitors for
      [125I][Leu31,Pro34]PYY binding in transfected cells. Additionally, the efficacy
      of the transfection method used was evaluated at both the transcriptional and
      translational levels. In situ hybridization revealed the heterogeneous
      distribution of the NPY Y1 receptor mRNA expressed in transfected HEK 293 cells.
      Similarly, the levels of NPY Y1 binding sites per transfected cell varied as
      shown using [125I][Leu31,Pro34]PYY receptor autoradiography. Taken together,
      these results demonstrate that HEK 293 cells transfected with the NPY Y1 receptor
      cDNA expressed both the related receptor mRNA and protein albeit at different
      levels depending upon each transfected cell. Additionally, these data further
      establish the selectivity of the newly developed Y1 and Y2 radioligands.

PMID- 8750832
TI  - Differential expression of inducible transcription factors in basal ganglia
      neurons.
AB  - The dopamine receptor antagonist, haloperidol, produced a time-dependent
      differential induction of inducible transcription factors (ITFs) in rat striatal
      neurons: Fos, Fos B, Jun B, Jun D, Krox 20, and Krox 24, but not c-Jun, were
      induced in the caudate putamen and nucleus accumbens with varying time courses.
      The induction of Fos by haloperidol was stronger in anterior versus posterior
      regions of the striatum. In contrast, induction of Fos by the muscarinic agonist
      pilocarpine was stronger in the posterior regions of the striatum suggesting that
      muscarinic receptors do not play a role in the induction of ITFs in striatal
      neurons by haloperidol. Although c-Jun was not induced in caudate neurons by
      haloperidol it was strongly induced in these neurons following prolonged seizure
      activity. The differential pattern of Jun protein expression suggests that
      haloperidol induces a specific transcriptional program in basal ganglia neurons.
      These effects of haloperidol may be involved in producing its extrapyramidal side
      effects.

PMID- 8750834
TI  - Time course of the induction of VGF mRNA in the dorsal vagal complex in rats with
      cysteamine-induced peptic ulcers.
AB  - The time course of induction of VGF mRNA in the dorsal vagal complex of the
      medulla oblongata was investigated in rats with duodenal ulcer induced with
      cysteamine by in situ hybridization histochemistry. In control rats, weak VGF
      mRNA signals were detected in a few neurons in the nucleus tractus solitarii and
      dorsal motor nucleus of vagus. After the cysteamine administration (450 mg/kg,
      s.c.), VGF mRNA signals began to increase after 3 h, reached at peak level at 12
      h, and decreased slightly at 24 h, but remained high after 48 h. The time course
      of duodenal ulcer score was absent at 3 h, very low at 6 h, about grade 1 at 12
      h, and grade 2 or more at 24 and 48 h. The present results support the hypothesis
      that the increase of the central neuronal activity of the vagus nerve precedes
      ulcer generation in the duodenum.

PMID- 8750835
TI  - Adenovirus-mediated gene transfer of dopamine D2 receptor cDNA into rat striatum.
AB  - A robust feature of mammalian aging associated with diminished motor control is
      the loss of dopamine D2 receptors from the neostriatum. Decline in this
      neurotransmitter receptor is also observed in neurodegenerative disorders, such
      as Huntington's disease and late-stage Parkinson's disease. We have constructed a
      replication-deficient adenoviral vector to transfer rat dopamine D2 receptor cDNA
      to brain as a possible therapeutic strategy. Using tissue culture cells infected
      with this vector, we detected dopamine D2 receptor mRNA by Northern analysis and
      functional receptor protein in membrane preparations as specific binding of the
      dopamine D2 receptor ligand, [3H]spiperone. In vivo demonstration involved
      autoradiographic analysis of [3H]spiperone binding in rat striatum following
      injection of the adenoviral vector. Dopamine D2 receptor expression was amplified
      markedly above normal concentrations in the injection site, whereas no increased
      expression was observed in sites receiving control treatments. These results
      demonstrate the potential of gene therapy using adenoviral vectors to transfer
      neurotransmitter receptor proteins to the brain to reverse deficiencies in
      specific neurodegenerative disorders.

PMID- 8750836
TI  - Cellular localisation and co-expression of somatostatin receptor messenger RNAs
      in the human brain.
AB  - Genes for five high affinity somatostatin receptors, named sst1-5, have been
      cloned recently. In this study we describe the tissue distribution and cellular
      localisation of mRNA encoding sst1, sst3 and sst4 receptors in the human
      cerebellum, frontal cortex (Brodmann's area 11) and hippocampus. RT-PCR and in
      situ hybridisation studies indicated a distinct, but partially overlapping
      pattern of expression of the receptor mRNAs. In situ hybridisation studies using
      co-expression techniques with probes for sst1, sst3 and sst4 receptor mRNA on
      paraffin sections revealed the presence of neurones expressing more than one
      somatostatin receptor mRNA type in both the hippocampus and pyramidal cells of
      layer V of the frontal cortex.

PMID- 8750837
TI  - HSP70 heat shock protein induction following global ischemia in the rat.
AB  - Stress proteins, including the 70 kD heat shock protein (HSP70), are induced in
      injured cells. The present study was designed to characterize the cells injured
      by global ischemia in rat brain. Adult rats were subjected to forebrain ischemia
      using bilateral carotid occlusion and systemic hypotension. HSP70 protein
      immunostaining of brain sections was performed using the C92 monoclonal antibody
      one day later. HSP70 immunoreactive cells were found in many brain regions
      including cortex. HSP70 positive neurons in cortex were found in certain laminae,
      especially layers 2 and 3. Acid fuchsin positive neurons, cells presumed to be
      dead, were located only in the layers of cortex where HSP70 immunoreactive
      neurons were found and were infrequent compared to the large number of HSP70
      positive neurons. HSP70 immunoreactive glial cells were detected at the margins
      of ischemic areas, and were mostly OX42 immunoreactive microglia plus some GFAP
      immunoreactive astrocytes. In some animals HSP70 stained bipolar cells were
      detected in the striatum and in white matter which may be type 2 astrocytes.
      These findings confirm that global ischemia injures microglia and astrocytes, and
      that cells in a given ischemic region sustain varying degrees of injury--from the
      HSP70 stained neurons that likely survive the ischemia to acid fuchsin stained
      cells that die.

PMID- 8750838
TI  - Ontogeny of aromatase messenger ribonucleic acid and aromatase activity in the
      rat midbrain.
AB  - Estrogen formation catalyzed by neural aromatase is crucial for the sexual
      differentiation of the brain. Ontogenic expression of aromatase mRNA and
      aromatase activity were studied in male and female rat midbrains. Aromatase mRNA
      was transiently expressed in both sexes showing maximum levels on postnatal day
      (P)2 and being absent on P20 and in adults. Developmental expression of aromatase
      mRNA preceded that of aromatase activity. These data demonstrate that the
      capacity for estrogen formation is present during a distinct phase of midbrain
      development. Our findings suggest an active role for estrogens in the
      differentiation of midbrain neurons.

PMID- 8750839
TI  - Molecular cloning and expression of alpha parvalbumin in the guinea pig cochlea.
AB  - We have cloned and sequenced an alpha parvalbumin cDNA from the guinea pig
      cochlea. The deduced amino acid sequence shows greater identity with the rabbit
      sequence (86.3%) than with other mammalian sequences (< 82%). Using in situ
      hybridization and immunohistochemistry, alpha parvalbumin mRNA and protein were
      found in primary auditory neurons and inner hair cells, in agreement with RT-PCR
      data showing alpha parvalbumin mRNA expression in the spiral ganglion and the
      organ or Corti.

PMID- 8750840
TI  - Protein F1/GAP-43 and PKC gene expression patterns in hippocampus are altered 1-2
      h after LTP.
AB  - Three days after long-term potentiation (LTP) there is a decrease in the gene
      expression of protein F1 (GAP-43) and gamma-PKC in CA3 pyramidal cells that is
      correlated with the magnitude of LTP. We predicted these decreases would be
      preceded by an increment in gene expression. At 1 h, but not at 2 h after LTP,
      F1/GAP-43 and gamma-PKC mRNA hybridization were increased, but increases were
      also observed after control stimulation. At both 1 and 2 h after LTP, changes in
      F1/GAP-43 hybridization were positively correlated with gamma-PKC hybridization
      and negatively correlated with LTP magnitude. These data indicate that correlated
      alterations in F1/GAP-43 gene expression and synaptic efficacy can occur as early
      as 1 h after LTP and persist for days.

PMID- 8750841
TI  - Hydroxyl radical scavengers enhance nitric oxide-evoked acetylcholine release
      from mouse cerebral cortical neurons.
AB  - The effect of hydroxyl radical scavengers on acetylcholine (ACh) release evoked
      by nitric oxide (NO) generators and N-methyl-D-aspartate (NMDA) was investigated.
      Dimethylthiourea enhanced dose-dependently NO generators-evoked ACh release.
      Similarly, uric acid and mannitol significantly facilitated ACh release evoked by
      NO generators. The NMDA-induced ACh release was also significantly facilitated by
      hydroxyl radical scavengers. These scavengers themselves showed no effects on ACh
      release. These results suggest that hydroxyl radicals may modify the mechanism
      for NO-evoked ACh release.

PMID- 8750842
TI  - Fos is not involved in the regulation of the proenkephalin gene by haloperidol in
      the mouse striatum.
AB  - The aim of the study was to determine whether the haloperidol-produced induction
      of the c-fos gene in the mouse striatum is the cause of the increased expression
      of the striatal proenkephalin (PENK) gene after repeated haloperidol
      administration. Mice were treated with haloperidol (1 mg/kg, i.p., once daily),
      MK-801 (1 mg/kg, i.p., twice daily), or with both those drugs for 9 days.
      Pretreatment with MK-801 prevented the haloperidol-produced induction of the
      striatal c-fos mRNA. In animals injected with haloperidol for 9 days, levels of
      the striatal PENK mRNA were increased by 100%. Coadministration of MK-801 did not
      reduce that increase. These results suggest that Fos is not necessary for
      activation of the PENK gene expression, produced by chronic haloperidol
      application, in the striatum.

PMID- 8750843
TI  - Ethanol stimulates diazepam binding inhibitor (DBI) mRNA expression in primary
      cultured neurons.
AB  - Changes in expression of diazepam binding inhibitor (DBI) mRNA in cerebral
      cortical neurons following long-term ethanol (EtOH) exposure were examined. A
      significant increase in DBI mRNA expression was observed by the exposure of
      neurons to 50 mM EtOH for up to 5 days and to EtOH (1-100 mM) for 3 days. These
      EtOH-induced increases in DBI mRNA expression were further elevated after the
      additional cultivation of neurons under EtOH-free condition. beta-Actin mRNA
      expression was not altered by similar EtOH treatments. These results indicate
      that EtOH possesses the activity to increase the expression of DBI mRNA in
      cerebral cortical neurons.

PMID- 8750844
TI  - Light damage revisited: converging evidence, diverging views?
AB  - Are observations on ultraviolet (UV)- and visible light-induced ocular changes in
      animals relevant for human pathology? Different conclusions are drawn by
      different groups, depending on their perspective: while in the epidemiologist's
      view the evidence for those lesions is mostly limited or insufficient, laboratory
      scientists continually extend observations on radiation damage in animals.
      Consequently, there are diverging views on the necessity and specifications for
      eye protection. In this review, problems of epidemiological surveys and
      observations in humans and animal studies are discussed, and natural and
      artificial protection of the eye is outlined. The human and animal eye has an
      inherent potential for photochemical lesions due to chromophores including the
      visual pigments that are present at birth. Lifelong light exposure gives rise to
      additional absorbing molecules. With decreasing wavelengths of the
      electromagnetic spectrum the number of absorbing molecules rises; therefore, the
      likelihood of a photochemical reaction grows. As the spectral energy is
      augmented, more damage will occur. In our view, the knowledge gained from
      laboratory studies is a significant component of the total evidence from
      different fields-epidemiology, clinical observations, model studies and
      theoretical calculations-that UV radiation and short-wavelength visible light can
      cause acute and chronic changes in ocular structures. Such changes may comprise
      irreversible damage. Following recently issued recommendations of the major
      visual health organizations in the United States, protection against UV and blue
      light should be incorporated into the spectrum of safety considerations for
      sunglasses.

PMID- 8750845
TI  - Blood-aqueous barrier in pseudoexfoliation syndrome: evaluation by
      immunohistochemical staining of endogenous albumin.
AB  - BACKGROUND: Alterations of the integrity of the blood-aqueous barrier (BAB) are
      frequent findings in eyes with pseudoexfoliation syndrome (PSX). METHODS:
      Immunohistochemical staining for the demonstration of albumin was used to analyze
      the BAB in 10 eyes with PSX without previous intraocular surgery and in 10 age
      matched normal control eyes. RESULTS: In eyes with PSX, small amounts of albumin
      were detected along the anterior surface of the iris in 7, in the anterior
      chamber in 1, along the ciliary epithelium in 4, and in the trabecular meshwork
      in 9 of 10 eyes. PSX material was also immunoreactive. In the 10 normal control
      eyes, albumin was detected anterior to the iris stroma in 1 eye, in the anterior
      chamber in 2 eyes, in the trabecular meshwork in 1 eye, but not internal to the
      ciliary epithelium. CONCLUSIONS: Our findings indicate that impairment of the BAB
      in PSX can be localized at the level of the iris and, less frequently or to a
      lesser extent, at the level of the ciliary body.

PMID- 8750846
TI  - Immunohistochemical studies of glycosaminoglycans in nanophthalmic sclera.
AB  - BACKGROUND: It has been observed that there may be some connection between
      scleral collagen changes, glycosaminoglycan (GAG) changes and nanophthalmic uveal
      effusion. In a previous paper we reported increased dermatan sulfate (DS) and
      chondroitin sulfate (CS) contents in nanophthalmos sclera using biochemical
      analysis. In the present work we used immunohistochemical methods to assess the
      GAG changes in nanophthalmos sclera. METHODS: Scleral specimens from three
      nanophthalmic patients and five controls were processed to immunostaining with
      peroxidase-antiperoxidase (PAP) methods. Monoclonal antibodies for chondroitin
      (Ch), chondroitin-4-sulfate (C4S), chondroitin-6-sulfate (C6S), DS and keratan
      sulfate (KS) were used. The specimens were observed under a light microscope.
      RESULTS: Nanophthalmos scleral samples exhibited strong KS staining compared with
      the control specimens. Both the nanophthalmos and the control samples were
      stained with anti-Ch, anti-C4S, anti-C6S and anti-DS antibodies to the same
      intensity. CONCLUSION: Our results suggest that an increased or abnormal
      distribution of KS may contribute to abnormalities in collagen fibers.

PMID- 8750847
TI  - Indocyanine green angiography and age-related serous pigment epithelial
      detachment.
AB  - BACKGROUND: Fundus fluorescein angiography has shown that pigment epithelial
      detachment in age-related macular degeneration is often associated with choroidal
      neovascularisation (CNV). Indocyanine green angiography (ICG-A) provides a better
      visualisation of choroidal circulation and of CNV than fluorescein angiography
      (FA). METHODS: We studied the ICG angiograms of 58 eyes presenting age-related
      pigment epithelial detachment, either with signs of occult CNV (48 eyes) or
      without signs of CNV (10 eyes) on FA. In selected cases the neovascular complex
      defined on the ICG angiogram was photocoagulated. RESULTS: ICG-A revealed
      hyperfluorescence interpreted as CNV in 46 of 48 eyes with fluorescein
      angiographic signs of occult choroidal neovascularisation. The neovascular
      complex seen on the ICG angiogram was well delineated in 29 eyes and ill defined
      in 17 eyes. ICG-A revealed CNV in 2 of 10 eyes without signs of CNV on FA. In
      these two cases the neovascular complex was ill defined. Photocoagulation in
      selected cases resulted in stabilisation or even improvement of visual acuity and
      flattening of the pigment epithelial detachment in 9 of 18 cases. CONCLUSION: ICG
      A may offer a better definition of the neovascular complex associated with
      pigment epithelial detachment in age-related macular disease and be helpful in
      guiding laser treatment. In some cases FA still outlines more clearly the lesions
      to be treated. FA and ICG-A should thus be used concurrently to determine
      treatment strategy.

PMID- 8750848
TI  - HLA expression and tumor-infiltrating immune cells in uveal melanoma.
AB  - BACKGROUND: In uveal melanoma, both the amount of tumor-infiltrating cells and
      the level of expression of HLA antigens are quite variable. We hypothesized that
      low levels of HLA expression lead to a lack of antigen presentation, which might
      prevent proper immunologic recognition of the tumor. This lack of recognition
      might subsequently lead to low levels of tumor-infiltrating cells. METHODS: To
      test this hypothesis, we determined the type and number of tumor-infiltrating
      cells in tumor sections from 24 uveal melanomas. We applied monoclonal antibodies
      directed against different types of immune cells and compared the results with
      the expression of HLA class I and class II antigens on the tumor cells. RESULTS:
      Infiltrating immune cells were observed in all uveal melanomas (although in small
      amounts), with a predominance of T lymphocytes. Significant positive correlations
      were observed between the number of CD3+ cells (T lymphocytes) and monomorphic
      HLA class I expression, allele-specific HLA-A2 and Bw4 expression, and HLA class
      II expression. Furthermore, the number of CD4+ cells (T helper cells, monocytes/
      macrophages) and of CD11b+ cells (monocytes/macrophages) was significantly
      correlated with the level of monomorphic HLA class I expression. CONCLUSION:
      These data support our hypothesis that low levels of HLA expression (and
      therefore a lack of presentation of tumor-specific antigens) may lead to a low
      level of tumor infiltrate.

PMID- 8750849
TI  - Hypoxia precedes the development of experimental preretinal neovascularization.
AB  - BACKGROUND: Although the mechanism of preretinal neovascular growth in the cell
      injected rabbit eye model is not known, it has been proposed that the initial
      vasodilation and eventual development of neovascularization may be attributable
      to inflammatory mediators. However, an alternative explanation involving hypoxia
      has not been considered. The purpose of this study was to measure preretinal
      oxygen tension prior to the development of preretinal neovascularization in the
      cell-injected rabbit eye. METHODS: In the rabbit, intravitreous injections of
      250,000 homologous dermal fibroblasts were performed on one eye; the fellow
      (control) eye was injected with vehicle. Preretinal oxygen tension over the
      myelin wing was measured using 19F-NMR spectroscopy of a 30-microliters droplet
      of perfluorocarbon previously injected into the preretinal vitreous. RESULTS:
      Compared to control eyes, fibroblast-injected eyes showed a 1.7-fold decrease in
      preretinal oxygen tension from the first time studied (1 day after cell
      injection) through the development of visible neovascularization. Hypoxia
      occurred without coexisting ophthalmoscopic evidence of vascular occlusion or, on
      days 1 and 3 after cell injection, retinal detachment. CONCLUSION: This result
      demonstrates for the first time that preretinal hypoxia precedes the development
      of preretinal neovascularization in the fibroblast-injected rabbit eye.

PMID- 8750850
TI  - Evidence of cross-link formation of vitreous collagen during experimental ocular
      inflammation.
AB  - PURPOSE: To determine the mechanisms of vitreous changes during ocular
      inflammation. METHODS: We investigated vitreous changes, with special emphasis on
      collagen, in an experimental model of ocular inflammation induced by intravitreal
      injection of endotoxin (Escherichia coli) in rabbits. RESULTS: Inflammation
      caused gel contraction and loss of elasticity, accompanied by release of a water
      like liquid from the gel, and increases in the amount of insoluble material and
      high-molecular-weight components of vitreous collagen, presumably due to
      extensive cross-links of the collagen molecules. Those changes were partially
      inhibited by intravitreal injection of superoxide dismutase. CONCLUSIONS: The
      cross-links of vitreous collagen may promote vitreous gel contraction and release
      of a water-like liquid from the gel. Superoxide anion may play a role in this
      process.

PMID- 8750851
TI  - Intraocular silicone lenses in silicone oil: an experimental study.
AB  - BACKGROUND: To evaluate a potential effect of silicone oil on flexible silicone
      intraocular lenses, four lenses (STAAR AA-4203) were stored in silicone oil under
      sterile conditions for periods between 1 month and 3 years. METHOD: The edge and
      surface of the lenses were examined by scanning electron micrography and the
      findings compared with a lens of the same model which had been stored in Ringer's
      solution for 2 years. RESULTS: After 1 year of silicone oil exposure, droplets of
      different sizes adherent to the surface of the lens were found. These changes
      proceeded to a wave-like appearance of the surface after 2 and 3 years of
      storage, so that a continuous layer of silicone oil polymers is probably covering
      the intraocular lens. CONCLUSION: Optical interference has to be considered a
      possibility if it turns out that the droplets cannot be removed during silicone
      oil evacuation. Consequently silicone intraocular lenses without hydrophilic
      preparation of the surface should not be implanted in eyes undergoing combined
      anterior and posterior segment surgery with silicone oil tamponade or in eyes
      with high risk for vitreoretinal complications.

PMID- 8750852
TI  - Influence of oxygen free radicals and free radical scavengers on the growth
      behaviour and oxidative tissue damage of bovine retinal pigment epithelium cells
      in vitro.
AB  - PURPOSE: This investigation was carried out to ascertain whether oxygen free
      radicals can influence the growth behaviour and consecutive lipid peroxidation of
      retinal pigment epithelium (RPE) cells in vitro and whether scavengers can
      counteract these effects. METHODS: The experimental model was based on calf RPE
      cells. Hypoxanthine/xanthine oxidase (HX/XO) and superoxide dismutase/ catalase
      (SOD/CAT) served as the radical generating system and scavengers, respectively.
      The components were tested alone and in combination. Lipid peroxides were
      determined in culture supernatants by a thiobarbituric acid assay. RESULTS:
      Concentrations of up to 100 mumol/l of HX alone and 500/ 1000 microU of XO alone,
      as well as the application of the scavengers without the radical generating
      system (HX/XO), had no effect. Dose-related reduction of cell growth and increase
      of lipid peroxidation were found with HX/XO treatment (single dose of 500 and
      1000 microU/ml 24 h after seeding). After application of 500 or 1000 microU/ml of
      XO, CAT, when given alone (1200 U/ ml), counteracted the effect of the radicals
      on cell growth and lipid peroxidation; SOD (300 U/ml) had no effect. A
      combination of SOD and CAT was no better than the effect of CAT alone.
      CONCLUSION: The prevention of radical-induced reduction of cell growth and lipid
      peroxidation by scavengers supports trials of therapy using antioxidants and/or
      free radical scavengers for various ocular syndromes with RPE involvement.

PMID- 8750853
TI  - Inhibition of fibroblast proliferation by human iris pigment epithelial cells in
      vitro: preliminary results.
AB  - BACKGROUND: The interaction between different cells plays an important role in
      many physiological and pathological processes. Since the proliferation of
      fibroblasts is very much involved in the pathogenesis of eye diseases such as
      proliferative vitreoretinopathy, the failure of filtration in glaucoma surgery,
      etc., we attempted to ascertain whether iris pigment epithelial cells (IPE) have
      some modulating effect on fibroblast proliferation. METHODS: Human IPE were
      explanted and the third-passage culture was transferred into serum-free RPMI-1640
      medium. After 48 h of further incubation, the medium was collected and submitted
      to centrifugation; the supernatant was used as the conditioned medium of IPE (IPE
      CM). Cultured fibroblasts from Tenon's capsule were seeded in a 96-well plate and
      incubated with IPE-CM in different concentrations. The proliferation of
      fibroblasts was estimated by thymidine incorporation and cell counting. RESULTS:
      The incorporation of tritiated thymidine by fibroblasts was reduced to 56.68% of
      baseline with 1:16 diluted IPE-CM and to 13.63% and 8.20%, respectively, with 1:8
      and 1:2 diluted IPE-CM. These findings were in good accordance with the results
      of cell counting, performed in parallel. SDS-PAGE of IPE-CM revealed two specific
      bands with molecular weight 65 kDa and 40 kDa. CONCLUSION: IPE-CM showed an
      obvious dose-dependent inhibitory effect on fibroblast proliferation and was
      presumed to contain some active factors contributing to this effect.

PMID- 8750854
TI  - The use of tissue plasminogen activator in post-traumatic total hyphaema.
AB  - BACKGROUND: We wanted to evaluate whether intracameral injection of tissue
      plasminogen activator (tPA) is useful in managing traumatic hyphaema. METHODS:
      Two eyes with total hyphaema after a severe penetrating injury were treated with
      a single intracameral injection of 25 micrograms of tPA 5 and 14 days after the
      injury, respectively. RESULTS: Most of the blood coagulum dissolved within 24 h,
      and in one of the two eyes the intraocular pressure decreased from 45 to 8 mmHg.
      The other eye was hypotonic. No re-bleeding or complications related to the use
      of tPA were noticed. CONCLUSION: The results in these two cases suggest that tPA
      is a useful adjunct in managing total hyphaema.

PMID- 8750855
TI  - Limits of two-dimensional planimetry in the follow-up of glaucomatous optic
      discs.

PMID- 8750856
TI  - Overexpressed tau protein in cultured cells is phosphorylated without formation
      of PHF: implication of phosphoprotein phosphatase involvement.
AB  - Pyramidal neurons in affected regions of Alzheimer's disease (AD) brain contain
      neurofibrillary tangles (NFT), aggregates of paired helical filaments (PHF)
      composed mainly of phosphorylated microtubule-associated protein tau. To explore
      the role of tau phosphorylation in the aggregation of tau into PHF, we
      constructed mammalian cell culture systems producing high levels of intracellular
      phosphorylated tau. COS-1 fibroblast-like cells were transiently transfected to
      simultaneously express tau, MAP kinase (MAPK), and MAP kinase kinase (MAPKK), or
      alternatively to express tau and glycogen synthase kinase 3 (GSK3). B103 neuron
      like cells (which contain MAPK but little tau or GSK3) were stably transfected to
      express tau or tau and GSK3. In both systems, GSK3-transfected cells contained
      tau AT8/M (defined by AT8 staining and tau PHF-like mobility), but MAPK
      transfected cells required phosphatase inhibitors, such as okadaic acid (OKA) or
      calyculin (CAL), to produce tau AT8/M. In vitro, the same concentrations of CAL
      and OKA inhibit phosphatases 1 and 2A (PP1 and PP2A), except that 100-1000 times
      as much OKA is needed to inhibit PP1. Inducing tau phosphorylation at the AT8
      site in MAPK-transfected cells required 2-10 times more OKA than CAL, suggesting
      both PP1 and PP2A helped block the phosphorylation. Though levels of tau AT8/M
      reached 2-8% of total cellular proteins in COS-1 cells, the ratio of particulate
      to supernatant tau levels did not increase, and no tangles were observed; perhaps
      post-translational modifications or co-aggregating proteins are needed to induce
      PHF.

PMID- 8750857
TI  - Differential spatio-temporal expression of the insulin-like growth factor genes
      in regenerating sciatic nerve.
AB  - Previous studies have demonstrated that the regeneration of mammalian peripheral
      nerves is dependent on endogenous insulin-like growth factors (IGFs). In the
      present study, in situ hybridization was used to examine the temporal and spatial
      expression of the IGF-I and IGF-II genes in rat sciatic nerve after crush. Such
      expression was characterized in relation to Schwann cell proliferation and the
      presence of neurofilaments in returning axons during regeneration. The results
      show that both IGF-I and IGF-II mRNAs were increased in the sciatic nerve distal
      to the crush site. However, each transcript had a distinctly different temporal
      and spatial distribution during regeneration. IGF-I gene expression was intensely
      increased at the crush site within 4 days after nerve crush. Along the portion of
      the nerve distal to the crush site, a moderate increase was observed to reach
      maximal levels 10 days postcrush, and was decreased thereafter back towards
      baseline at 20 days postcrush. Furthermore, this increase was associated with the
      proliferation of Schwann cells, and the return toward baseline with the
      regeneration of axons containing neurofilaments. By contrast, IGF-II gene
      expression was unchanged at or near the site of injury, but unexpectedly was
      increased in more distal, intramuscular reaches of the nerves. This had a slower
      time course beginning 10 days postcrush, and was further increased at 20 days
      postcrush. These results show that the IGF-I and IGF-II genes are regulated by
      independent signals and probably play different roles during nerve regeneration.
      They support the hypotheses that IGF-I contributes to the initial sprouting and
      subsequent elongation of axons in nerves, whereas IGF-II enhances the
      regeneration of certain axons into neuromuscular branches of nerves, and/or the
      re-establishment of neuromuscular synapses.

PMID- 8750858
TI  - Chronic exposure to stress levels of corticosterone alters GABAA receptor subunit
      mRNA levels in rat hippocampus.
AB  - Chronic exposure to stress levels of corticosteroids alters many aspects of
      hippocampal function and may lead to neurodegeneration. Male rats were treated
      for 10 days with corticosterone (CORT) or vehicle pellets, and mRNA levels for
      six gamma-aminobutyric acid (GABAA) receptor subunits were measured. Effects of
      castration on subunit mRNA levels in CORT- and vehicle-treated animals were also
      examined. In situ hybridization studies demonstrated that mRNA levels for
      hippocampal GABAA receptor alpha 1, alpha 2, beta 1, beta 2, beta 3, and gamma 2
      subunits were differentially altered by CORT treatment. Levels of alpha 1 and
      alpha 2 mRNA decreased in the dentate gyrus, and beta 1 mRNA levels decreased in
      CA1 and dentate gyrus of CORT-, compared to vehicle-treated, animals. In
      contrast, beta 2 subunit levels increased in all hippocampal regions examined,
      beta 3 levels increased in the dentate gyrus, and gamma 2 levels increased in CA1
      CA3. The alpha 1, beta 1, and beta 2 mRNA levels all increased in the cingulate
      cortex of CORT-treated animals. There was no significant effect of gonadal state
      on any of the subunits examined, but there was a significant negative correlation
      between testosterone levels and mRNA levels of alpha 1, alpha 2 and beta 3 in
      specific regions. These data demonstrate that chronic exposure to stress levels
      of CORT produces complex changes in the mRNA levels of multiple GABAA receptor
      subunits, independently of the CORT-induced suppression of circulating
      testosterone.

PMID- 8750859
TI  - Differential expression of fetal and mature tau isoforms in primary cultures of
      rat cerebellar granule cells during differentiation in vitro.
AB  - The molecular mechanism(s) responsible for the differential expression of various
      tau protein isoforms as well as their functional role in morphogenesis,
      neurofibrillary tangle formation and neurodegeneration have not been completely
      clarified. We found that the expression of tau proteins in primary cultures of
      cerebellar granule cells from neonatal rat brain is a developmentally regulated
      process affecting tau synthesis at different levels. Changes in tau RNA splicing
      are clearly demonstrated by PCR data showing the switching on of the mRNA
      containing four internal repeats by DIV 6 and the switching off of the mRNA
      containing three internal repeats after DIV 12. The changes in mRNA levels of the
      different tau isoforms during development in vitro occur in parallel with changes
      in tau protein expression, both qualitatively and quantitatively, as shown by
      Western analysis of protein extracts from granule cells at different DIV with an
      anti-tau polyclonal antibody. Finally, as indicated by MAP2 and tau
      immunocytochemistry data, the switch in tau protein expression appears to be
      contemporary with neurite outgrowth and cell differentiation. Our data suggest
      that a differential expression of various tau proteins parallels the degree of
      cell maturation.

PMID- 8750860
TI  - Characterisation of GABAA receptor gamma subunit expression by magnocellular
      neurones in rat hypothalamus.
AB  - Gamma-aminobutyric acid (GABA) is known to inhibit the electrical and secretory
      activity of oxytocin and vasopressin neurones located in the supraoptic and
      paraventricular nuclei following osmotic, cardiovascular or suckling stimuli. To
      understand fully the nature of GABA actions on these magnocellular neurones it is
      important to define the heteropentameric GABAA receptor proteins they express. In
      the present study, single and dual labelling in situ hybridisation and
      immunocytochemical experiments were undertaken to define the GABAA receptor gamma
      subunits expressed by these cells. In situ hybridisation with 35S-labelled
      antisense oligonucleotides showed that all magnocellular neurones in the
      supraoptic and paraventricular nuclei of the female rat expressed mRNA encoding
      the gamma 2 subunit of the GABAA receptor but not the gamma 1 or gamma 3
      subunits. Immunocytochemical experiments using a specific polyclonal rabbit
      antibody directed against the gamma 2 subunit of the GABAA receptor showed that
      all hypothalamic magnocellular neurones were strongly immunoreactive for gamma 2
      subunit protein. Dual in situ hybridisation experiments using the gamma 2 subunit
      35 S-labelled oligonucleotide with alkaline phosphatase-labelled antisense
      oligonucleotides specific for either oxytocin or vasopressin revealed that
      essentially all oxytocin and vasopressin neurones in both the supraoptic and
      paraventricular nuclei expressed the gamma 2 subunit of the GABAA receptor.
      Similarly, sequential double immunoperoxidase staining revealed that all oxytocin
      and vasopressin neurones in both magnocellular nuclei of the hypothalamus were
      immunoreactive for the gamma 2 subunit. This study shows that only the gamma 2
      subunit of the GABAA receptor gamma subunit family is expressed by hypothalamic
      oxytocin and vasopressin neurones. In conjunction with our previous results,
      these findings indicate that individual magnocellular neurones express a
      complement of alpha 1, alpha 2, beta 2, beta 3 and gamma 2 subunits of the GABAA
      receptor. The observation of strong gamma 2 subunit expression by neurones known
      to also express alpha 1 and alpha 2 subunit proteins suggests that these
      magnocellular cells may express GABAA receptors with both benzodiazepine type-1
      and type-2 pharmacology.

PMID- 8750862
TI  - Differential regulation of mRNA levels encoding for the two isoforms of glutamate
      decarboxylase (GAD65 and GAD67) by dopamine receptors in the rat striatum.
AB  - The effects of in vivo administration of dopamine receptor agonists or
      antagonists on the mRNA levels encoding for the two isoforms of glutamate
      decarboxylase, GAD65 and GAD67, and for preproenkephalin were studied in regions
      of the rat dorsal striatum by radioactive in situ hybridization histochemistry.
      Changes in striatal mRNA levels after drug treatment were quantified by
      computerized densitometry on X-ray films. Chronic administration of the dopamine
      receptor agonist apomorphine or the D1 dopamine receptor agonist SKF-38393
      resulted in increased GAD65 mRNA levels in the dorsomedial, ventromedial,
      dorsolateral and ventrolateral sectors of the striatum. Apomorphine or SKF-38393
      treatment did not induce significant effects on GAD67 and preproenkephalin mRNA
      levels in striatum. On the other hand, chronic administration of the D2 dopamine
      receptor agonist quinpirole significantly decreased GAD67 in the dorsolateral and
      ventrolateral and preproenkephalin in the ventrolateral sectors of the striatum.
      Quinpirole treatment did not induce significant changes in GAD65 mRNA levels.
      Chronic administration of the dopamine receptor antagonist haloperidol resulted
      in a significant increase in GAD67 and preproenkephalin mRNA levels in the
      dorsomedial, dorsolateral and ventrolateral striatal sectors. Chronic treatment
      with the D2/D3 dopamine receptor antagonist sulpiride resulted in a significant
      increase in GAD67 in the ventromedial and ventrolateral and PPE in the
      dorsomedial and ventrolateral striatal sectors. Haloperidol or sulpiride did not
      induce significant changes in striatal GAD65 mRNA levels. Chronic administration
      of the D1 dopamine receptor antagonist SCH-23390 had no significant effect on
      GAD67, GAD65 or preproenkephalin mRNA levels. In the present experimental
      conditions, stimulation of dopamine receptors with apomorphine or SKF-38393
      resulted in increased GAD65 mRNA levels whereas blockade of dopamine receptors
      with haloperidol or sulpiride resulted in increased GAD67 mRNA levels. These
      results indicate that striatal GAD65 and GAD67 mRNA levels are differentially
      regulated by dopamine receptor subtypes.

PMID- 8750861
TI  - Increased levels of statin, a marker of cell cycle arrest, in response to
      hippocampal neuronal injury.
AB  - Injured neurons in the CNS are known to synthesize high levels of proliferation
      related oncogene products and heat shock proteins without dividing. Statin is a
      cell cycle regulated nuclear phosphoprotein, selectively associated with the non
      proliferative state in a wide variety of cell types. In the present study,
      neuronal statin was examined following lethal or sublethal neuronal injuries in
      the hippocampus of Alzheimer's disease patients, in rats receiving kainate
      lesions to the dorsal hippocampus and in entorhinal cortex lesioned rats.
      Immunolabelling of nuclear statin showed that statin immunoreactivity increased
      preferentially in CA1 pyramidal neurons of the hippocampus in Alzheimer's
      disease. In kainate lesioned rats, statin immunoreactivity was markedly induced
      in the CA3 hippocampal region in association with neuronal loss. Entorhinal
      cortex lesioned rats showed a transient induction of statin between 2 and 6 days
      post lesion in CA1 neurons. However, cell counts in entorhinal cortex lesioned
      rats remained unaltered in the CA1 and granule cell layers during the entire 30
      day time course, indicating that increased statin levels are not secondary to
      neuronal degeneration and are not necessarily accompanied by irreversible
      neuronal death. It is concluded that, in addition to proliferation related gene
      products, neuronal injury induces an increase in levels of statin, a nuclear
      marker of cell cycle arrest. Furthermore, statin may be a potentially useful
      marker of injurious neuronal stress, even under conditions that do not
      necessarily lead to irreversible cell death.

PMID- 8750863
TI  - Messenger RNAs encoding steroidogenic enzymes are expressed in rodent brain.
AB  - Using the reverse transcription polymerase chain reaction, mRNAs encoding
      steroidogenic P450s as well as NADPH-cytochrome P450 reductase (P450 reductase),
      adrenodoxin and the transcription factor steroidogenic factor 1 (SF-1) were all
      detected in rodent brain, but their distribution between brain regions varied.
      Adrenodoxin and P450 reductase were detected in all regions, suggesting the
      presence of both mitochondrial and microsomal P450s throughout the brain.
      Messenger RNAs encoding P450scc (CYP11A1) and P45017 alpha (CYP17) were also
      detected in all brain regions, this being the first report of CYP17 in the brain.
      P450c21 (CYP21) was detected only in the brain stem. P45011 beta (CYP11B1) and
      P450aldo (CYP11B2) are expressed in rat brain, but not in mouse brain; CYP11B1
      primarily in the cerebrum, whereas CYP11B2 was detected in all brain regions. In
      both species, highest levels of aromatase P450 (CYP19) mRNA were detected in the
      cerebrum. SF-1 expression was restricted to the cerebrum minus cortex. Thus,
      although SF-1 is required for high level expression of the steroidogenic enzymes
      in adrenals and gonads, other factors may influence the expression of these genes
      in the brain. If the mRNAs detected by RT-PCR are indeed translated into
      functional enzymes, these studies suggest that different brain regions have
      different capacities for local steroid hormone production and metabolism. This
      raises the technical challenge of locating the specific sites of synthesis as
      well as the function of such locally produced ligands.

PMID- 8750864
TI  - Type II brain sodium channel expression in non-neuronal cells: embryonic rat
      osteoblasts.
AB  - Although voltage-sensitive sodium channels play a central role in electrogenesis
      in neurons, rat brain sodium channels are also present in some glial cells. To
      determine whether rat brain sodium channel alpha-subunit isotypes are expressed
      in other cell types, we examined osteoblasts within the embryonic day 17 (E17)
      vertebral column with in situ hybridization and immunocytochemical methods. For
      in situ hybridization studies, riboprobes hybridizing to isoform-specific
      sequences in the 3'-noncoding region of sodium channel mRNAs (NCI, NCII and
      NCIII) were utilized. Sodium channel mRNA I and III were not detectable in
      osteoblasts of the vertebra centrum or neural arches in E17 rats. In contrast,
      sodium channel mRNA II was moderately expressed by osteoblasts in the developing
      vertebral column of E17 rats. In immunocytochemical experiments, antipeptide
      antibodies directed against conserved and isotype-specific regions of the sodium
      channel alpha-subunit were used. Antibody SP20, which recognizes a conserved
      region of the sodium channel, intensely stains osteoblasts in both the vertebra
      centrum and neural arches. Antibody SP11-I, which recognizes sodium channel I,
      exhibited negligible-to-low levels of immunostaining in vertebral column
      osteoblasts. Osteoblasts reacted with antibody SP11-II, which recognizes sodium
      channel II, displayed moderate levels of immunostaining. Antibody SP32-III, which
      recognizes sodium channel III, displayed negligible levels of staining in
      osteoblasts within vertebra centrum and neural arches. These results demonstrate
      that osteoblasts in situ within E17 vertebral columns express sodium channel II
      mRNA and protein. Together with previous electrophysiological observations, the
      present results suggest that functional sodium channels are expressed in
      osteoblasts in vivo. These results extend the range of non-neuronal cells known
      to express rat brain sodium channels.

PMID- 8750865
TI  - Changes in blood volume and pressure induce c-fos expression in brainstem neurons
      that project to the paraventricular nucleus of the hypothalamus.
AB  - Immunohistochemistry for c-fos was combined with retrograde tracing techniques to
      study the effects of acute reductions in arterial blood pressure due to
      hemorrhage (HEM) in conscious rats on activated neurons in the brainstem nucleus
      of the tractus solitarius (NTS) or ventrolateral medulla (VLM) which project to
      the paraventricular nucleus (PVN) of the hypothalamus. In an attempt to separate
      blood pressure effects from those associated with changes in blood volume, a
      similar approach was used to study the effects of drug-evoked hypotension using
      peripheral infusions of sodium nitroprusside (NP). Few differences were found in
      patterns or numbers of activated neurons (Fos-immunoreactive) in the NTS or VLM
      after HEM or NP treatment; only in the NTS at the level of the area postrema were
      significantly higher numbers of neurons that expressed Fos found in NP rats. In
      addition, a large proportion of PVN-projecting neurons in the NTS and VLM was
      activated whereas many activated neurons in the NTS and VLM did not project to
      the PVN. These results show that a decrease in blood pressure leads to the
      activation of NTS and VLM neurons but that a change in blood volume does not
      activate significantly greater numbers of neurons in these areas that project to
      the PVN or to other targets. Whereas substantial numbers of neurons in the NTS
      and VLM appear to transmit cardiovascular information to the PVN, many others
      likely transmit this information to other central targets.

PMID- 8750866
TI  - alpha 2-Adrenergic receptors in human spinal cord: specific localized expression
      of mRNA encoding alpha 2-adrenergic receptor subtypes at four distinct levels.
AB  - alpha 2-Adrenergic receptor (AR) subtype mRNA (alpha 2a, alpha 2b, alpha 2c)
      neuronal localization in human spinal cord has not been described. We therefore
      performed in situ hybridization to identify cell bodies at four levels of human
      spinal cord (cervical, thoracic, lumbar, sacral) containing alpha 2AR subtype
      specific mRNA. alpha 2AR mRNA is present in gray matter only (ventral > dorsal;
      sacral > cervical > thoracic = lumbar). In addition to alpha 2AR mRNA in cell
      bodies in thoracic and lumbar intermediolateral (sympathetic) and sacral
      intermediate (parasympathetic) cell columns (lamina VII), all levels in dorsal
      horn laminae I, II, V, and ventral horn lamina IX, we demonstrate alpha 2AR mRNA
      in dorsal horn laminae III and IV, and dorsal nucleus of Clarke, where alpha 2ARs
      have not been described. Previously unreported heterogeneity in alpha 2AR subtype
      distribution (alpha 2a and alpha 2bAR mRNA present, alpha 2cAR mRNA virtually
      absent) is found at all sites of alpha 2AR mRNA expression in human spinal cord,
      including locations known to mediate effects of alpha 2AR agonist drugs on
      nociception, autonomic function and motor tone. Cervical spinal cord demonstrates
      a predominance of alpha 2a mRNA signal, while thoracic, lumbar, and sacral spinal
      cord demonstrate an increasing predominance of alpha 2bAR mRNA. If confirmed at a
      protein level, these findings have profound implications for therapeutic
      strategies in managing human pain.

PMID- 8750867
TI  - beta-Amyloid regulates gene expression of glial trophic substance S100 beta in C6
      glioma and primary astrocyte cultures.
AB  - S100 beta, a calcium-binding protein synthesized by CNS astrocytes, has trophic
      effects in vitro (neurite extension and glial proliferation). In Alzheimer's
      disease and Down's syndrome, severely afflicted brain regions exhibit up to 20
      fold higher levels of S100 beta protein, and astrocytes surrounding neuritic
      plaques exhibit highly elevated levels of S100 beta immunostaining. A major
      constituent of plaques, beta-amyloid, has been reported to have neurotoxic and
      neurotrophic effects in vitro. In our study we examined the responses of CNS glia
      to beta-amyloid. C6 glioma cells and primary rat astrocyte cultures were treated
      with beta A(1-40) peptide at doses up to 1 microM. Weak mitogenic activity,
      measured by [3H]thymidine incorporation, was observed. Northern blot analysis
      revealed increases of S100 beta mRNA within 24 h in a dose-dependent manner.
      Nuclear run-off transcription assays showed that beta A(1-40) specifically
      induced new synthesis of S100 beta mRNA in cells maintained in serum, but under
      serum-free conditions, there was a general elevation of several mRNA species.
      Corresponding increases of S100 beta protein synthesis were observed by
      immunoprecipitation of 35S-labeled cellular proteins. To evaluate whether this
      effect of beta-amyloid was mediated via neurokinin receptors or by calcium
      fluxes, various agonists and antagonists were tested and found to be ineffective
      at stimulating S100 beta synthesis. In sum, these in vitro data suggest that in
      neuropathological conditions, beta-amyloid itself is an agent which may provoke
      chronic gliosis and the production of trophic substances by astrocytes.

PMID- 8750868
TI  - Application of quantitative RT-PCR to the analysis of dopamine receptor mRNA
      levels in rat striatum.
AB  - A quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) procedure
      has been developed which selectively amplifies and quantifies the two isoforms of
      the dopamine D2 receptor. Variability is corrected by the inclusion of a D2
      dopamine receptor mRNA standard within each reaction. The internal standard was
      generated by introducing a point mutation within a D2 cDNA clone that created a
      unique restriction site within the amplified region. An in vitro transcribed RNA
      for the internal mutant control is added to the RNA isolated from brain tissue
      and the mixture is subjected to RT-PCR, digestion with the restriction enzyme,
      separation of the products by PAGE, and quantification by direct analysis of
      radioactivity incorporated during the PCR step. The standard is amplified, in the
      same reaction as the experimental RNA, using the same primers and RT-PCR
      conditions. In this manner, the effects of contaminants of the RNA preparation
      which could affect the amplification procedure are assessed. To insure that the
      amplification is linear, the number of PCR cycles is minimized. This adaptation
      avoids 'competitive PCR' and provides for a linear response. Moreover, to obviate
      non-specific co-amplification, primer annealing steps are performed at or above
      the melting temperature for the primers, thus increasing signal-to-noise ratios.
      Finally, primer pairs have been designed which permit amplification of specific
      fragments for each of the five rat dopamine receptor subtypes. These fragments
      have unique sizes and so can be differentiated when simultaneously amplified in
      the same RNA preparations.

PMID- 8750869
TI  - Comparative expression of vasopressin and angiotensin type-1 receptor mRNA in rat
      hypothalamic nuclei: a double in situ hybridization study.
AB  - Angiotensin II (Ang) injected intracerebroventricularly stimulates
      neurohypophyseal vasopressin (AVP) release into the peripheral circulation. As we
      have shown previously, central actions of Ang II in the rat forebrain are
      mediated by the AT1A receptor subtype. In the present paper, we attempted to
      clarify the cellular localization of the AT1A receptor mRNA in the hypothalamic
      paraventricular (PVN) and supraoptic (SON) nuclei, in order to reappraise the
      conflicting data on the nature of the angiotensin II receptor involved in Ang
      induced vasopressin release. For this purpose, double in situ hybridization was
      performed using a radioactive AT1A receptor riboprobe and a digoxygenin labeled
      AVP oligoprobe, and immunohistochemical localization of the glial marker glial
      fibrillary acidic protein (GFAP) on the same brain slice. The results show
      neuronal expression of AT1A receptor mRNA mainly in dorsal and medial
      parvocellular parts of the PVN, its localization in some magnocellular PVN
      neurons and the absence of its expression in AVP producing neurons either in the
      PVN or in the SON. Thus, while indirect evidence indicates the involvement of the
      AT1A receptor subtype in the regulation of CRH and oxytocin release, the
      stimulation of vasopressinergic neurons is likely due to indirect mechanisms, or
      to a yet unknown type of angiotensin receptor.

PMID- 8750870
TI  - Sexually dimorphic expression of calcitonin gene-related peptide (CGRP) mRNA in
      rat medial preoptic nucleus.
AB  - Previous immunocytochemical analyses have identified a substantial, gonadal
      steroid-dependent sex difference in the number of cells expressing calcitonin
      gene-related peptide (CGRP) in the rat preoptic area. Using three 35S-labelled
      antisense oligonucleotide probes specific for both alpha and beta CGRP, the
      present study has examined CGRP mRNA expression within the medial preoptic
      nucleus (MPN) of intact and gonadectomised male and female rats. Cells expressing
      CGRP mRNA were found to be more numerous in the intact female (21 +/- 2
      cells/hemisection) compared with the male (6 +/- 1; P < 0.01) although the
      average CGRP mRNA content of MPN cells was not different between intact males (62
      +/- 7 silver grains/cell) and females (69 +/- 6 silver grains/cell). Gonadectomy
      resulted in a significant increase in the number of CGRP mRNA expressing cells
      detected in the male (12 +/- 1 cells/hemisection; P < 0.01) and an increase (P <
      0.05) in the mean CGRP mRNA content per cell in both males (99 +/- 12 silver
      grains/cell) and females (107 +/- 11 silver grains/cell). These results show that
      sex differences exist in the number of cells containing CGRP transcripts in the
      rat MPN although average CGRP mRNA content per cell is not different between
      males and females. Gonadal steroids appear to exert a tonic suppressive influence
      on the CGRP mRNA content of MPN cells in both males and females.

PMID- 8750871
TI  - Localization of mRNA for phosphatidylinositol 3-kinase in brain of developing and
      mature rats.
AB  - In the adult brain, the gene expression for phosphatidylinositol 3-kinase was
      weak in almost all neurons with relatively high levels in the olfactory bulb,
      hippocampus, and cerebellum. On the embryonic days high levels of the gene
      expression were found throughout the entire neuraxis, then decreased gradually to
      adult levels during postnatal development. The present finding suggests that
      phosphatidylinositol 3-kinase may contribute not only to neurogenesis but also to
      some important physiological roles in differentiating and mature neurons.

PMID- 8750872
TI  - Localization of novel receptor tyrosine kinase genes of the eph family, MDK1 and
      its splicing variant, in the developing mouse nervous system.
AB  - In the course of studies to identify new members of the eph family of receptor
      tyrosine kinases, MDK1 and one of its splicing variants lacking a kinase domain,
      MDK1-T1, were identified. To gain insight into the functions of these subtypes,
      expression patterns of their mRNAs in the developing mouse nervous system were
      examined by Northern blotting and in situ hybridization histochemistry.
      Colocalization of their mRNAs was observed, but the levels of expression of each
      mRNA were developmentally regulated. These findings suggest functional
      differences between full-length and truncated forms of MDK1 receptor tyrosine
      kinase.

PMID- 8750873
TI  - Basal expression of 35 kDa fos-related antigen in olfactory bulb.
AB  - Recently, there have been a number of reports showing a long-term increased
      expression of fos-related antigens (fra), molecular weight of 35 kDa, after brain
      injury or chronic treatment of rats with various drugs. We report elevated basal
      levels of this transcription factor in the olfactory bulb relative to other brain
      regions. The expression of this protein is further enhanced in the olfactory bulb
      as long as 3 months after a single injection of kainate, an effect similar to
      that we previously observed in the hippocampus. The AP-1 DNA binding activity in
      olfactory bulb from kainate-treated rats contains fra and jun immunoreactivity
      suggesting that the 35 kDa fra dimerizes with jun protein, probably junD, to bind
      to AP-1 sites. Elevated basal levels of this transcription factor in the
      olfactory bulb appear to be related to the constant reinnervation and
      synaptogenesis which occurs in this brain region. The 35 kDa fra may be involved
      in long-term genomic program changes required to adapt to an altered biochemical
      environment.

PMID- 8750874
TI  - Localization of Fas antigen mRNA induced in postischemic murine forebrain by in
      situ hybridization.
AB  - The expression of mRNA for the Fas antigen, a membrane-associated protein
      mediating apoptosis, was localized by in situ hybridization histochemistry in
      murine brains following 30 min of global cerebral ischemia. Six hours following
      the ischemia, many labeled cells were detected anew throughout the brain. The
      hybridization was seen in the small neural cells and in the cells along the walls
      of the ventricles and vessels, and became undetectable 24 h following the
      ischemia. These results suggest that the Fas antigen is expressed in the neuron,
      glia and periventricular cells of the post-ischemic brain.

PMID- 8750875
TI  - Prion disease associated with a novel nine octapeptide repeat insertion in the
      PRNP gene.
AB  - Some cases of spongiform encephalopathies are linked to mutations within the
      prion protein gene (PRNP). Repetitive octapeptide insertions of variable length
      in the PRNP gene are also associated with spongiform encephalopathies, mostly
      familial Creutzfeldt-Jakob disease (CJD). In this study we report on a novel
      insertion mutation comprising nine extra octapeptide repeats between codons 51
      and 91 of the PRNP gene. The affected patient showed a slowly progressive
      dementia of at least 6 years duration and ataxia.

PMID- 8750876
TI  - Synchronous patchy pattern of gene expression for adenylyl cyclase and
      phosphodiesterase but discrete expression for G-protein in developing rat
      striatum.
AB  - The ontogeny of the gene expression for striatal adenylyl cyclase (AC), 63 kDa
      calmodulin-dependent phosphodiesterase (63 kDa CaM-PDE) and olfactory G-protein
      (Golf), all of which are expressed predominantly in the striatum, was studied by
      in situ hybridization histochemistry. In the peri- and early postnatal striatum,
      the gene expression for striatal AC and 63 kDa CaM-PDE showed a patchy pattern
      corresponding to the striatal patchy compartments enriched in several molecules
      involved in cAMP-signaling system including DARPP-32 (a dopamine and cyclic
      adenosine 3':5'-monophosphate-regulated phosphoprotein with an apparent M(r) of
      32,000). On the other hand, Golf showed a homogeneous expression pattern
      throughout the striatal development. The present finding suggests that the gene
      expression for the three molecules directly involved in the cAMP-generating and
      degrading system is differentially regulated during the striatal development.

PMID- 8750877
TI  - The Xenopus laevis homologue to the neuronal cyclin-dependent kinase (cdk5) is
      expressed in embryos by gastrulation.
AB  - Phosphorylation of the neuronal cytoskeletal proteins NF-H, NF-M and tau is
      important for normal axonal development, and is involved in axonal injury and
      neurodegenerative diseases. In mammalian neurons, one kinase that phosphorylates
      these axonal cytoskeletal proteins is cyclin-dependent kinase 5 (cdk5). Cdk5 is a
      member of the family of cyclin-dependent kinases (cdks), whose other family
      members regulate mitosis. Unlike the other cdks, cdk5 is abundant in
      differentiated neurons. Embryos of the clawed frog Xenopus laevis have proved
      useful for studying other cyclin-dependent kinases, neurofilament proteins and
      tau during development. As a first step in studying the role of cdk5 and its
      effects on neurofilaments during Xenopus neural development, four cDNA clones
      were isolated by screening a frog brain cDNA library at lowered stringency with a
      cDNA probe to rat cdk5. The frog cdk5 clones encoded a protein of 292 amino acids
      that was 97% identical to rat cdk5. In situ hybridization demonstrated that the
      Xenopus cdk5 transcript, like that of mammals, was expressed in differentiated
      post-mitotic neurons. The high degree of sequence homology and shared neuronal
      expression suggests that the role of cdk5 in neurons is highly conserved between
      mammals and amphibians. Northern blot analysis indicated that during Xenopus
      development, cdk5 mRNA was first expressed between the midblastula transition and
      gastrulation, which both occur long before neuronal differentiation. These stages
      mark the transition from synchronous to asynchronous cell division and are the
      earliest stages of zygotic gene expression. This early expression of Xenopus cdk5
      mRNA implies a role for cdk5 during embryogenesis that is separate from its role
      as an axonal cytoskeletal protein kinase. These observations provide the
      foundation for exploiting X. laevis embryos to study the role of cdk5 both in the
      early stages of axonal differentiation and also in early embryogenesis.

PMID- 8750878
TI  - Regulation of angiotensinogen gene expression in the rat forebrain by adrenal
      steroids and relation to salt appetite.
AB  - The renin-angiotensin system (RAS) is present in the brain where it participates
      in regulation of fluid-electrolyte homeostasis and possibly plays a role in
      arousal of salt appetite. In the present studies using quantitative in situ
      hybridization histochemistry we examined the level of the angiotensinogen (ANG)
      mRNA in the forebrain areas associated with fluid-electrolyte balance in
      adrenalectomized (ADX) rats and ADX rats supplemented either with selective
      glucocorticoid type II receptor agonist RU 28362 or with the selective type I
      receptor agonist, aldosterone (ALDO). RU 28362 and ALDO were administered for 7
      days via Alzet 2001 osmotic minipumps at the rates of 10 micrograms/microliters/h
      and 1 microgram/microliter/h, respectively. Following adrenalectomy, rats were
      maintained on a standard rat chow, water and 3% NaCl ad lib. In situ
      hybridization was performed either with a synthetic [33P]- or [32P]-3' end
      labeled oligonucleotide probe and the level of ANG mRNA was detected by grain
      counting over a single cell or by quantitative film autoradiography,
      respectively. Seven days post ADX the ANG mRNA level in all studied forebrain
      areas -septum-diagonal band of Broca (SEPT/DBB), the areas immediately adjacent
      to the organum vasculosum of the lamina terminalis (OVLT), the median preoptic
      nucleus (MnPO), and the medial preoptic area (mPOA)-of ADX rats decreased by 50
      60%. ALDO treatment, which did prevent ADX-induced saline ingestion, did not
      prevent this decrease. However, supplementation with RU 28362 maintained normal
      levels of ANG mRNA in all the above regions of the brain. Thus the expression of
      the ANG gene in the studied areas of rat forebrain is predominantly under the
      control of the adrenal glucocorticoids via the type II receptor and not regulated
      by an ALDO dose that stabilizes natriuresis from the kidney.

PMID- 8750879
TI  - Effect of adrenal steroids on preproneurokinin-A gene expression in discrete
      regions of the rat brain.
AB  - An in situ hybridization histochemical procedure was developed to monitor the
      cellular distributions of the three major alternatively spliced alpha, beta and
      gamma species of mRNA encoding neurokinin molecules of the CNS. Two
      oligodeoxyribonucleotide probes were synthesized corresponding to common
      sequences of the alpha, beta, and gamma NK-A mRNA. The first experiment used rats
      that were sham-operated (Sham), adrenalectomized (ADX), and ADX rats treated with
      corticosterone (ADX+CORT). Intense labelling was observed within the habenula
      (Hb), while strong labelling was detected within the olfactory tubercle (OT), the
      lateral olfactory tubercle (LOT), the horizontal diagonal band of Broca (HDB),
      the bed nucleus of the stria terminalis (BNST), and the dorsal and ventral part
      of the caudate putamen (d-CP, v-CP). Moderate labelling of a number of cells was
      observed within the medial preoptic area (mPOA), the postero-dorsal part of the
      medial amygdala (MePD), and the dorsal and ventral part of the premamillary
      nucleus of the hypothalamus (PM-D; PM-V). ADX decreased NK-A mRNA in OT, LOT,
      HDB, BNST, CP compared to sham-operated rats, whereas CORT replacement elevated
      NK-A mRNA to above sham levels in OT, LOT, HDB, BNST and CP. There was no effect
      of ADX or CORT in Hb, while smaller, and often non-significant, effects of ADX
      and CORT replacement were found in other areas. Since there are two types of
      adrenal steroid receptors in brain, we next investigated the effects of agonists
      for type I and type II adrenal steroid receptors. ADX rats were given either
      aldosterone (ALDO, 10 micrograms/ml/h, Alzet minipumps) or RU 28362 (10
      micrograms/ml/h, Alzet minipumps) for 8 days. Type I receptor activation by ALDO
      partially reversed the ADX-induced decrease in NK-A mRNA, whereas type II steroid
      receptor activation by RU 28362 restored the decrease caused by ADX and caused an
      elevation of NK-A mRNA above sham levels in OT. These findings show that adrenal
      steroids regulate NK-A gene expression through both type I and type II receptors
      in a number of brain areas. The results are consistent with a role for adrenal
      steroids and neurokinins in the regulation of body fluid homeostasis.

PMID- 8750880
TI  - An orphan nuclear receptor, mROR alpha, and its spatial expression in adult mouse
      brain.
AB  - We have cloned cDNA encoding a mouse nuclear receptor mROR alpha which is a
      homolog of human retinoic acid receptor-related orphan receptor (hROR alpha).
      Cotransfection experiments revealed that mROR alpha activates transcription
      through a retinoic acid responsive element of the laminin B1 gene (lamRARE), but
      not through a RARE of RAR beta gene (beta RARE) or a synthetic palindromic
      thyroid hormone responsive element (TREpal). The most distal AGGTCA half-site
      among the three half-sites of lamRARE was sufficient for binding of mROR alpha
      and consequently for activation of transcription. Transactivation by mROR alpha
      was dependent on serum in culture medium after transfection, suggesting the
      presence of a possible ligand. Northern hybridization and in situ hybridization
      analyses revealed that mROR alpha is expressed in specific areas of the brain
      including thalamus and olfactory bulb as well as cerebellum where it is present
      at highest levels in Purkinje cells. In addition to regionally heterogeneous
      expression in brain, its expression was temporally regulated during
      differentiation of P19 cells into neural cells, but not into muscle cells. These
      observations suggest that mROR alpha plays important roles as a transcription
      factor not only in differentiation of neural cell lineages but also in the mature
      brain.

PMID- 8750881
TI  - Prenatal morphine exposure differentially alters expression of opioid peptides in
      striatum of newborns.
AB  - The biochemical and cellular mechanisms involved in the development and/or
      maintenance of morphine tolerance remain unclear. In the adult central nervous
      system (CNS) results are contradictory. For the neonate, a variety of drug
      induced deficits have been observed following prenatal addiction to opioids,
      although very little work on the biochemical and molecular level has been done.
      Therefore, the present study was carried out to investigate the effects of
      prenatal morphine treatment on the levels and expression of endogenous opioid
      peptides in brain regions of newborns. Dams were implanted with one morphine
      pellet (75 mg each) 1 week prior to the birth of pups. Changes in mRNA levels for
      the opioid peptides were determined by Northern blot analysis. Alterations in
      opioid peptide levels were determined by radioimmunoassays. Prenatal morphine
      treatment significantly increased proenkephalin mRNA levels and decreased met
      enkephalin levels in striatum of newborns. These data are in contrast to what is
      observed in the adult CNS. These data indicate that prenatal morphine treatment
      may increase met-enkephalin release and/or cause inhibition at the level of
      translation. In addition, increased transcription may be necessary to maintain
      equilibrium in the system when there is an increase in met-enkephalin release.

PMID- 8750882
TI  - Nerve growth factor-regulated properties of sensory neurones in Oct-2 null mutant
      mice.
AB  - The POU-domain transcription factor Oct-2 is expressed in both B lymphocytes and
      sensory neurones, where its expression is regulated by nerve growth factor (NGF).
      In order to define a possible role for Oct-2 in neurotrophin signalling, we
      examined the expression of an NGF-regulated channel (capsaicin-evoked ion
      fluxes), neuropeptides (substance P, calcitonin gene-related peptide), structural
      proteins (neurofilaments and peripherin) and receptors (trks) in dorsal root
      ganglion neurones derived from perinatal transgenic mice containing a defective
      Oct-2 structural gene. Northern blots show that central nervous tissue contains a
      larger than normal (> 10 kb) mRNA transcript corresponding in size to an Oct-2
      transcript encoding a defective protein. PCR analysis shows the absence of normal
      Oct-2 transcripts in dorsal root ganglia. In null mutants, capsaicin sensitivity,
      and neuropeptide and cytoskeletal protein expression were unaffected by the loss
      of Oct-2 expression. The number of sensory neurones and the gross morphology of
      CNS tissues that normally express high levels of Oct-2 were also examined and
      found to be normal in the null mutant. Heterozygous animals show normal
      thresholds of sensitivity to noxious heat and normal inflammatory responses. Oct
      2 does not therefore play an essential role in the NGF responsiveness of sensory
      neurones in these animals.

PMID- 8750883
TI  - Transcriptional activation of Alzheimer's beta-amyloid precursor protein gene by
      stress.
AB  - A neuropathological hallmark of Alzheimer's disease (AD) is the neuritic plaque,
      composed of an extracellular cluster of degenerating nerve terminals with a
      central core that is in part composed of deposits of a 4 kDa beta-amyloid
      peptide. Over-expression of the amyloid precursor protein (beta-APP) gene could
      be a contributing factor in the aberrant processing of the precursor protein,
      possibly leading to the formation of beta-amyloid. In AD the brain exhibits
      several features which indicate that neurons affected by AD exist under
      conditions of stress. Although the heat shock consensus sequence (CTCGACTTTTCTAG)
      located at position -317 bp is among the regulatory elements of the beta-APP
      gene, suggesting that this may act in the regulation of the beta-APP gene in
      response to stress, an induction of beta-APP as a result of interaction of this
      element with a heat shock factor has so far not been demonstrated. Moreover,
      there are conflicting reports in the literature regarding the up-regulation of
      beta-APP with stress. In this study we have used a fragment of the beta-APP
      promoter which includes the heat shock element, cloned into a luciferase
      expression vector pxP2 to transiently transfect cultured human NT2 and HeLa
      cells. Our findings directly demonstrate that transcription of the beta-APP gene
      is stimulated by various stresses--increase in temperature, treatment with
      ethanol and sodium arsenite. Gel mobility shift assays confirm the interaction of
      the heat shock element with a heat shock factor, induced as a result of stress.

PMID- 8750884
TI  - The role of signal transduction systems in mediating cell density dependent
      changes in tyrosine hydroxylase gene expression.
AB  - Cell density has been implicated in the regulation of neuronal gene phenotype.
      This study tested the interaction of signal transduction pathways and the
      expression of tyrosine hydroxylase (TH) mRNA with varying cell density.
      Increasing cell density in a parental, wild type PC12 cell line elevated steady
      state levels of TH mRNA. Three observations suggested that this induction is not
      related to the cyclic AMP dependent signalling pathway: (1) Forskolin stimulated
      the level of TH mRNA similarly at multiple densities. (2) PKA deficient mutant
      PC12 cell lines that have either one third (A123.7, AB11) or 3% (A126-1B2) of
      normal basal expression of TH mRNA still exhibit the same density induced
      elevation of TH mRNA levels as the wild type. (3) Different cell densities did
      not change cyclic AMP concentrations in the basal or in the receptor stimulated
      state. Increasing cell density did not change basal levels of inositol
      triphosphate (IP3) levels, which suggests that the phosphatidylinositol cascade
      (PI) is not responsible for density dependent changes in TH expression.
      Increasing confluence was highly correlated to [Ca2+]i in control (r = 0.70; P <
      0.0001), A123.7 (r = 0.92; P < 0.001), AB11 (r = 0.72; P < 0.0001) and A126 (r =
      0.42; P < 0.07). Taken together, the results show that neither cyclic AMP nor the
      PI cascade is involved in cell density induced changes in TH mRNA and suggest
      that altered [Ca2+]i may have a role.

PMID- 8750885
TI  - Role of amino acids in salivation and the localization of their receptors in the
      rat salivary gland.
AB  - The distribution of gamma-aminobutyric acid (GABA) receptor subunits such as
      GABAAR-gamma 1 and GABAAR-gamma 2, and alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) type receptor subunits such as GluR-1, GluR-2/3
      and GluR-4, and N-methyl-D-aspartic acid (NMDA) type subunits such as NR1 were
      investigated by immunocytochemistry. Furthermore, the roles of these amino acids,
      GABA and glutamate, on salivation were analyzed in the rat submandibular and
      sublingual glands. Some similarities were observed in the distribution patterns
      of GABAA type receptors and AMPA receptors. In the submandibular ganglion cells,
      collecting ducts and striated ducts, these subunits were expressed strongly;
      however, there were some differences in their expression patterns between the
      submandibular and sublingual gland acinar cells. Since these receptor subunits
      were expressed in the acinar cell bodies of the submandibular gland, they were
      not expressed in the acinar cells but were expressed in the myoepithelial cells
      in the sublingual gland. On the other hand, no NR1 expression was observed. To
      examine the roles of GABA and glutamate in salivation, the submandibular and
      sublingual glands were perfused partially with Ringer's solution via a facial
      artery to avoid systemic influence, and substrates were infused into the
      perfusion solution. No salivary secretion was evoked by GABA or glutamate
      infusion in the absence of electrical stimulation (2-3 V, 5 ms, 20 Hz). Salivary
      flow evoked by electrical stimulation of the chorda-lingual nerve caused
      significant inhibition by GABA (10(-6), 10(-5), 10(-4) and 10(-3) M) and the
      GABAAR agonist muscimol 10(-3) and 10(-6) M) (n = 6, P < 0.05). Such GABA-induced
      inhibition was antagonized by the GABAAR antagonists bicuculline (BCC; 10(-6) and
      10(-3) M) and picrotoxin (PTX; 10(-6) and 10(-3) M). On the other hand, salivary
      flow evoked by electrical stimulation (8-10 V, 5 ms, 20 Hz) of the superior
      cervical ganglion (SCG) was not affected by GABA. While high doses of glutamate
      (10(-1) M) and NMDA (10(-1) M) showed no effects on salivary flow despite
      application of electrical stimulation, AMPA at a high concentration (10(-1) M)
      significantly inhibited salivary secretion (n = 6, P < 0.05). These studies
      revealed that inhibitory and excitatory amino acid receptors such as GABAA and
      AMPA type receptors are coexpressed in the rat salivary glands, and that GABA
      inhibits salivary secretion via GABAA receptors which may act with acetylcholine.
      However, the role of glutamate in salivation remains unclear despite the presence
      of AMPA type receptors. The present findings suggest that glutamate does not act
      alone but with other substances such as peptides and/or other amino acids.

PMID- 8750886
TI  - Molecular and cellular analysis of rP1.B in the rat hypothalamus: in situ
      hybridization and immunohistochemistry of a new P-domain neuropeptide.
AB  - P-domain peptides, a new family of secretory polypeptides, have been identified
      mainly in the gastroenteropancreatic tract of humans, rodents, and amphibians as
      well as in amphibian skin. In the present study, with PCR and RNA analysis a
      transcript has been discovered in rat brain termed rP1.B. The deduced polypeptide
      consists of a single P-domain and its amino acid sequence matches that of rat
      intestinal trefoil factor (rITF). Thus far, rP1.B is the only P-domain peptide
      expressed in neuronal cells of the CNS. Immunostained magnocellular perikarya
      were visible in the paraventricular, supraoptic and periventricular nuclei.
      Parvocellular rP1.B neurons were found in the arcuate nucleus. Additionally,
      specific hybridization signals with radiolabeled transcripts were observed in the
      same regions. rP1.B in the rat hypothalamus may be involved in the control of
      hypothalamo-hypophysial functions.

PMID- 8750887
TI  - Expression of agrin mRNA is altered following seizures in adult rat brain.
AB  - Agrin mRNA is broadly distributed throughout the adult rat brain, consistent with
      its proposed role in synaptogenesis and the organization of synaptic proteins in
      the central nervous system. The present study examined the effect of neuronal
      activity on agrin mRNA expression in adult rat forebrain using the hilus lesion
      paradigm for seizure induction and in situ hybridization and polymerase chain
      reaction techniques for quantification and characterization of agrin mRNA
      content. Seizures induced rapid, prolonged, and region-specific changes in agrin
      mRNA expression with the most prominent alterations occurring in hippocampal and
      cortical neurons. However, there were no detectable perturbations in the relative
      abundance of alternatively spliced agrin transcripts in affected brain regions.
      Activity-dependent changes in agrin expression suggest a role for this protein in
      modifications of synaptic structure associated with functional synaptic
      plasticity.

PMID- 8750889
TI  - Elevated AP-1 transcription factor DNA binding activity at the onset of
      functional plasticity during development of rat sensory cortical areas.
AB  - The patterns of three transcription factor DNA binding activities, namely AP-1,
      Octamer and CREB, were examined in barrel and visual cortices of rat brain during
      early postnatal development, when activity-dependent plasticity of neuronal
      responses and connectivity was described. Main peak levels of AP-1 DNA binding
      activity have been observed at 21 days postnatally in both cortical areas. In
      addition, slightly elevated AP-1 levels were detected at 3-7 postnatal days in
      the barrel and in the visual cortex. In contrast, Octamer DNA binding activities
      were at the highest levels in both areas at 7 days postnatally, and CREB DNA
      binding activities were not appreciably modulated throughout the development. The
      AP-1 protein complex at 21 days postnatally was composed of JunD, JunB, Fra-2,
      FosB and to much lesser extent of c-Fos in both cortical areas. Treatment of 21
      day old rats with MK-801, an NMDA receptor antagonist, provoked a dramatic
      decrease in AP-1 DNA binding activities in the barrel cortex, but not in the
      visual cortex. Elevated AP-1 DNA binding activity can be taken as a good
      correlate of an onset of functional plasticity in the rat sensory cortex,
      although in the two primary sensory cortices examined it seems to be regulated in
      different ways.

PMID- 8750888
TI  - Expression of c-fos and hsp70 mRNA after traumatic brain injury in transgenic
      mice overexpressing CuZn-superoxide dismutase.
AB  - The aim of this study was to determine the role of oxidative stress on c-fos and
      hsp70 gene expression in transgenic (Tg) mice overexpressing CuZn-superoxide
      dismutase (SOD-1) following traumatic brain injury (TBI). hsp70 mRNA, as
      investigated using in situ hybridization, was induced around the lesion at 4 and
      24 h, but not at 1 and 48 h, in both Tg and non-transgenic (nTg) mice
      littermates. The degree of hsp70 induction was somewhat greater in nTg than Tg
      mice at 4 and 24 h after TBI. c-fos mRNA was induced throughout cortex,
      hippocampus, caudate putamen and the ventricular wall in Tg and nTg mice. TBI
      induced c-fos bilaterally in the cortex in both animals. There was a time
      dependent difference in cortical c-fos expression between nTg and Tg mice. The
      induction of c-fos mRNA in the striatum was greater in nTg at 24 h and decreased
      in both animals by 48 h. Edema of the injured cortex was significantly attenuated
      in Tg mice at all time points (1-48 h). These data show that the degree of hsp70
      induction and the degree, extent, and duration of c-fos induction produced by TBI
      are affected by levels of superoxide dismutase activity. It is proposed that
      superoxide radicals affect spreading depression and brain edema produced by TBI
      and that this effect may either directly or indirectly modulate the expression of
      the c-fos and hsp70 genes after TBI.

PMID- 8750890
TI  - Central glucoprivation evoked by administration of 2-deoxy-D-glucose induces
      expression of the c-fos gene in a subpopulation of neuropeptide Y neurons in the
      rat hypothalamus.
AB  - Central glucoprivation evoked by the intracerebroventricular administration of 2
      deoxy-D-glucose (2DG) induces eating and suppresses growth hormone (GH) secretion
      in rats. To elucidate the hypothalamic mechanism of these phenomena, the
      induction of c-fos gene expression was examined by in situ hybridization using
      rats with centrally administered 2DG. Autoradiography on X-ray film showed that c
      fos gene expression was transiently induced in discrete hypothalamic regions;
      namely the paraventricular nucleus, arcuate nucleus (ARC), the surrounding
      regions of the third ventricle dorsal to the ARC, and the periventricular nucleus
      (PeV). The time course of the expression was different in these nuclei. Double
      label in situ hybridization for c-fos mRNA and neuropeptide Y (NPY) or
      somatostatin mRNAs revealed that 20% of the NPY neurons in the ARC expressed the
      c-fos gene, while a small population of somatostatin neurons (6.1% in the ARC and
      2.6% in the PeV) expressed the c-fos gene following 2DG administration. Since NPY
      is an orexigenic neuropeptide and has an inhibitory effect on GH secretion, the
      data suggest that the activation of a subpopulation of NPY neurons in the ARC
      contributes, in part, to the increased food intake and suppression of GH
      secretion after central glucoprivation evoked by 2DG.

PMID- 8750891
TI  - Identification of rat serotonin 5-HT2C receptors as glycoproteins containing N
      linked oligosaccharides.
AB  - Antibodies against a portion of the rat 5-HT2C receptor third intracellular loop
      were generated and used to identify receptors solubilized from cell lines and rat
      brain. Western blots of CHAPS-soluble proteins were probed with affinity-purified
      anti-2C antibodies. The specificity of anti-2C was demonstrated with extracts
      prepared from NIH/3T3 fibroblasts which stably express functional rat 5-HT2C or 5
      HT2A receptors. Extracts from the 5-HT2C cell line, but not the 5-HT2A cell line,
      contained immunoreactive proteins with masses of 51-52 kDa and 58-68 kDa. In the
      brain, immunoreactive proteins were identified from choroid plexus extracts with
      masses of 51 kDa and 58-62 kDa. The major 58-62 kDa and minor 51 kDa proteins
      were not detected in extracts prepared from the hippocampus, striatum, or frontal
      cortex using the same amount of CHAPS-soluble protein. These results are
      consistent with previous studies demonstrating that 5-HT2C receptor binding sites
      and mRNA are most abundant in choroid plexus. The association of asparagine
      linked (N-linked) oligosaccharides with the receptors was examined next. The 5
      HT2C receptor cell line (3T3/2C) was grown in the presence of tunicamycin to
      metabolically inhibit N-linked glycosylation. Proteins from the cell extracts
      were detected with masses of 40 and 41 kDa. Extracts prepared from 3T3/2C cells
      (grown in the absence of tunicamycin) and from choroid plexus were incubated with
      N-glycosidase F to enzymatically remove available N-linked sugars. Immunoreactive
      proteins were detected with masses of 41 and 42 kDa from 3T3/2C cells and 41 kDa
      from choroid plexus. Neuraminidase, which cleaves sialic acid (N-acetylneuraminic
      acid) residues from glycoproteins, reduced the mass of the 51 and 58-62 kDa
      proteins from the choroid plexus to 50 and 54-58 kDa. In contrast, the 51-52 and
      58-68 kDa proteins from 3T3/2C cells were not affected by treatment with
      neuraminidase. These results demonstrate that 5-HT2C receptors contain N-linked
      sugars and suggest that sialic acid residues associate with 5-HT2C receptors in
      the choroid plexus. The oligosaccharide moieties, which contribute up to
      approximately 30% of the relative mass as judged by SDS-polyacrylamide gel
      electrophoresis, may impart functional properties to 5-HT2C receptors.

PMID- 8750892
TI  - Immunocytochemical localization of three subtypes of GABA transporter in rat
      retina.
AB  - Cellular distributions of three subtypes of GABA transporter (GAT1, GAT2, GAT3)
      in the eye were examined using polyclonal antisera for each subtype. GAT1 was
      present in the inner plexiform layer and proximal part of the inner nuclear
      layer, while GAT3 was distributed throughout the entire sensory retina, being
      predominant in the distal part of the inner plexiform layer and in the outer
      plexiform layer. GAT2 immunoreactivity was seen in the retina, including the
      retinal pigment epithelium layer and nerve fiber layer, also in the ciliary body
      epithelium. Confocal scanning laser fluorescence microscopy disclosed that the
      GAT1 immunoreactivity consisted of a number of small deposits in the inner
      plexiform layer and that GAT1-immunoreactive dots encircle immunonegative neurons
      in the inner nuclear layer. GAT2 immunoreactivity was present in the fiber bundle
      of the optic nerve and in the retinal pigment epithelium within the retina. GAT3
      immunoreactive cells had long processes running vertically throughout the sensory
      retina. GAT1 is suggested to be present mainly in the processes of amacrine cells
      and GAT3 to be distributed in Muller cells. We conclude that GAT1, GAT2 and GAT3
      are expressed in different cells, that they are involved in distinct GABAergic
      transmission in the retina, and that GAT2 may be involved in non-neuronal
      functions in the eye.

PMID- 8750893
TI  - Regulation of secretogranin II mRNA in rat neuronal cultures.
AB  - The regulation of SgII mRNA expression was investigated in primary cultures of
      neurons prepared from the hypothalamus and brainstem of 1-day-old rats. The
      administration of forskolin (FSK) resulted in a time- and dose-dependent increase
      in SgII mRNA expression, a 9-fold effect within 6 h being achieved with 10 microM
      FSK, which maximally increased cellular cAMP levels. SgII mRNA levels remained
      elevated for 24 h. Activation of protein kinase C with 100 nM phorbol 12
      myristate 13-acetate (PMA) also increased SgII mRNA expression, although
      induction with PMA was slower and more moderate (3.8-fold above control after 24
      h). Neither 10 microM 1,9-dideoxyforskolin nor 100 nM 4 alpha-phorbol 12,13
      didecanoate, inactive analogues of FSK and PMA respectively, had an effect on
      SgII mRNA. Depolarization of neuronal cultures with 50 mM KCl had a small and
      variable effect on SgII mRNA levels (1.8-fold above control) in neuronal cultures
      and did not influence induction with FSK. To investigate whether neuron-like
      regulation of SgII mRNA expression could be reproduced in PC12 cells, PC12 cells
      were treated with 100 nM nerve growth factor (NGF) for 7 days prior to challenge
      with FSK or PMA. Whereas NGF alone modestly increased SgII mRNA expression in
      PC12 cells (1.8-fold above control), it did not uncover a stimulatory effect of
      FSK or PMA. These studies indicate that SgII mRNA expression is enhanced by an
      increase in cellular cAMP and activation of protein kinase C in primary cultures
      of neurons and emphasize that SgII mRNA is regulated in a cell-specific manner.

PMID- 8750894
TI  - Dopamine D1 receptor, D2 receptor, proenkephalin A and substance P gene
      expression in the caudate nucleus of control and schizophrenic tissue: a
      quantitative cellular in situ hybridisation study.
AB  - The cellular expression of the mRNAs encoding the dopamine D1 receptor, dopamine
      D2 receptor and the neuropeptides enkephalin and substance P was determined in
      fresh frozen sections of human post-mortem caudate nucleus from control and
      schizophrenic brains using the technique of radioactive in situ hybridisation
      coupled with computer-assisted image analysis. Measurements of silver grain
      densities and mean cross-sectional somatic areas revealed no significant
      differences in the expression of any of these four gene transcripts. Further,
      cell count estimates revealed that each of these four mRNAs was expressed by
      approximately 20% of caudate cells (neurones and glia) in both control and
      schizophrenic tissue. These data demonstrate that the cellular expression of the
      dopamine D1 and D2 receptors and the neuropeptides enkephalin and substance P
      mRNAs are stable post mortem and that the relative cellular abundance of these
      mRNAs is not altered in the caudate nucleus of schizophrenic brains when compared
      to controls. These findings draw into focus the possible sites of action of
      clinically prescribed neuroleptics and suggest that chronic neuroleptic treatment
      of patients displaying negative schizophrenic symptoms may 're-set' an underlying
      neurochemical imbalance within the caudate nucleus.

PMID- 8750895
TI  - Regulation of neurotensin receptor mRNA expression by the receptor antagonist SR
      48692 in the rat midbrain dopaminergic neurons.
AB  - In this study, we demonstrated that the tyrosine hydroxylase-like immuno-reactive
      (possibly dopaminergic) neurons express neurotensin receptor mRNA in the rat
      substantia nigra and in the ventral tegmental area. Additionally, 2 weeks
      treatment with the neurotensin receptor antagonist SR 48692 increased mRNA levels
      in the substantia nigra. These data suggest that neurotensin receptor expression
      in the perikarya and in the terminal regions of dopaminergic neurons is regulated
      by its endogenous agonist in vivo.

PMID- 8750896
TI  - Protein kinase C inhibitor potentiates the agonist-induced GTPase activity in COS
      cell membranes expressing delta-opioid receptor.
AB  - In COS-7 cell membranes expressing cloned delta-opioid receptor, [D-Ser2,
      Leu5]enkephalin-Thr6, an opioid delta-agonist, showed no significant stimulation
      of high-affinity GTPase, while this agonist binding showed a guanine nucleotide
      sensitivity. Significant stimulation of GTPase activity by this agonist was
      observed only when the cells were pretreated with 0.1 microM calphostin C, a
      protein kinase C inhibitor, and when this inhibitor was further added to the
      reaction mixture at 1 microM. These findings suggest that protein kinase C is
      involved in the heterologous desensitization of delta-opioid receptor in the
      cells.

PMID- 8750897
TI  - Chronic opioid antagonist administration upregulates mu opioid receptor binding
      without altering mu opioid receptor mRNA levels.
AB  - Chronic administration of opioid antagonists has been shown to increase
      radioligand binding to brain opioid receptors. The present study was conducted to
      determine whether chronic exposure to the opioid antagonist naltrexone would
      similarly increase mu opioid receptor gene expression as measured by mRNA levels.
      Male Sprague-Dawley rats were administered naltrexone, 7-8 mg/kg/day, or saline
      by osmotic minipumps for 7 days. As expected, the density of mu opioid receptor
      binding sites was significantly higher in the brains of animals treated
      chronically with naltrexone as compared with saline-treated control animals.
      However, mu opioid receptor mRNA content determined by a solution hybridization
      RNase protection assay was not significantly altered in any brain region
      investigated. These results indicate that the upregulation of mu opioid receptors
      as measured by radioligand binding is not accompanied by increased levels of mu
      receptor mRNA.

PMID- 8750898
TI  - Metabolism of 2-thiobenzothiazoles in the rat. Urinary, fecal and biliary
      metabolites of 2-benzothiazyl sulfenamides.
AB  - Metabolic fates of 2-benzothiazyl sulfenamides, N-oxydiethylene-2-benzothiazyl
      sulfenamide and N-cyclohexyl-2-benzothiazyl sulfenamide in rats were studied
      using tracer technique. These compounds given orally to rats were excreted
      rapidly in the urine and feces. Five urinary metabolites, 2-mercaptobenzothiazole
      (MBT), its three conjugates, mercapturate, glucuronide and sulfate, and 2,2'
      dibenzothiazyl disulfide (BTDS) were confirmed. Furthermore, BTDS was found as a
      fecal metabolite. The sulfenamides were partly transformed in the stomach to
      BTDS, which was predominantly excreted into the feces. In the liver, the
      sulfenamides were mainly transformed to MBT and its conjugates. The S-glucuronide
      and S-sulfate conjugates were predominantly excreted into the bile. Mechanisms
      were discussed concerning the metabolite formation of sulfenamide derivatives in
      vivo and in vitro.

PMID- 8750899
TI  - N-Nitroso-N-(3-keto-1,2-butanediol)-3'-nitrotyramine. A new genotoxic agent
      derived from the reaction of tyrosine and glucose in the presence of sodium
      nitrite.
AB  - N-Nitroso-N-(3-keto-1,2-butanediol)-3'-nitrotyramine (NO-NTA) is a product of a
      model browning system in the presence of sodium nitrite. In this study, the
      chemical structure is confirmed by spectral studies, including UV, mass
      spectrometry, nuclear magnetic resonance and infrared spectroscopy. NO-NTA is
      strongly genotoxic to the rat hepatocyte and is moderately cytotoxic to mouse
      C3H10T1/2 cells. Results obtained in this study indicate that NO-NTA inflicted
      DNA damage through the formation of a DNA adduct. In addition, C3H10T1/2 cells
      were treated with NO-NTA and, following addition of 12-O-tetradecanoylphorbol-13
      acetate (TPA) as promotor, the increase of transformed foci indicated that NO-NTA
      could possibly be an initiator [corrected] of TPA tumor promotion. A transformed
      cell line from NO-NTA initiated and TPA promoted foci increased saturation
      density and growth ability in soft agar reactive to the control line. These
      results suggest that the formation of a genotoxic agent of nitroso-derivatives
      may take place in a nitrite-containing food system during processing and cooking.

PMID- 8750900
TI  - Methantheline improves the reactivation by HI 6 of human erythrocyte
      acetylcholinesterase inhibited by soman in vitro.
AB  - The effect of methantheline, a quaternary ammonium compound, on the reactivation
      by HI 6 of soman-inhibited human erythrocyte acetylcholinesterase (AChE) was
      investigated in vitro using purified human erythrocyte AChE or washed human
      erythrocytes. Methantheline itself was found to be a mixed competitive/non
      competitive inhibitor of AChE (Kii 360 +/- 70 mumol/l; Ki 240 +/- 10 mumol/l). In
      all experiments the enzyme was first inhibited by soman for 30 min under
      conditions preventing ageing (pH 10.0 degrees C) and then ageing was allowed by
      changing the pH to 7.3 and the temperature to 37 degrees C. Methantheline
      addition (0.36 or 3.6 mmol/l) at the start of ageing increased the portion of
      AChE which could be reactivated by HI 6 (0.32 mmol/l) added 5 min later, from
      24.6 +/- 1.0% (mean +/- SEM) of the original activity to 42.1 +/- 1.8% or 45 +/-
      2.9%, respectively. With HI 6 alone, the portion of AChE activity which could be
      reactivated 25 min after the start of ageing decreased rapidly with the delay of
      the oxime addition (100% of the original activity at immediate addition), the
      half-life being approximately 2.5 min. With methantheline alone (0.36 mmol/l) the
      AChE activity was lower after immediate addition (37% of the original value), but
      the loss of activity due to the increasing delay of methantheline addition
      exhibited a similar half-life as with HI 6. Finally, when methantheline (0.36
      mmol/l) was added at the start of ageing and HI 6 at various intervals thereafter
      the half-life of AChE activity loss due to the delay of HI 6 addition at least
      doubled, compared to incubations without methantheline.

PMID- 8750901
TI  - Treatment of organophosphate poisoning in pigs: antidote administration by a new
      binary autoinjector.
AB  - The therapeutic effectiveness of a new binary autoinjector containing 500 mg HI-6
      and 2 mg atropine sulphate was tested in anesthetized pigs poisoned by a lethal
      dose of soman i.v. (9 micrograms/kg per 20 min). Pharmacokinetics and
      pharmacodynamics of HI-6 were studied concomitantly on administration of HI-6
      alone, together with atropine sulphate, or together with atropine sulphate during
      soman intoxication. Cardiopulmonary parameters were monitored and serum
      concentrations of oxime and acetylcholinesterase (AChE) were measured in blood
      samples taken at intervals over a 6-h period postinjection. Five minutes after
      the start of soman infusion, mean AChE activity was decreased to 27 +/- 4.3% of
      baseline and signs of poisoning appeared. The antidotes, HI-6 and atropine
      sulphate, were then administered i.m. One minute after this injection there was a
      transient significant increase in AChE activity of 76 +/- 8.2% of baseline (p <
      0.01). It then again decreased and remained suppressed throughout the experiment.
      Mean respiratory rate was significantly decreased (p < 0.01) to 20 +/- 3.2% of
      baseline after 20 min of soman infusion and remained low during the rest of the
      experiment. The poisoning signs were counteracted 15-20 min after antidote
      therapy and all pigs survived soman intoxication without ventilatory assistance.
      Administration of either atropine or atropine and soman had no significant effect
      on the pharmacokinetics of HI-6 in anesthetized pigs.

PMID- 8750902
TI  - Fulvic and humic acids decrease the absorption of cadmium in the rat intestine.
AB  - Dissolved organic carbon (DOC) in drinking water is mainly composed of fulvic and
      humic acids, which may form complexes with metal ions. The influence of DOC on
      the intestinal absorption of Cd in the rat was investigated using an "isolated
      intestinal segment" technique in anaesthetised rats. The lumens of segments were
      exposed for 60 min to different concentrations of CdCl2 and DOC in intact
      animals. The fractional absorption (FA) was not dose dependent in the dosage
      interval 0.01-0.03 microgram Cd/kg. However, at 15 and 150 micrograms Cd/kg both
      FA and intracellular Cd distribution in the segments were dose dependent, which
      is in line with results from other studies performed on similar experimental
      models. In the presence of 1 and 10 mg DOC/l, FA of Cd was just half as high as
      FA in animals that received Cd alone (0.01 microgram/kg). Moreover, a higher
      percentage of Cd was associated with the metallothionein fraction in the
      intestinal segment of the DOC-dosed rats. An in vitro speciation experiment
      showed that only 0.2-7.9% of the Cd in the incubation solution was complexed to
      DOC. In deionized water, however, more than 99% of the Cd was complexed to DOC.
      This result indicates that the incubation solution contained substances that
      negatively affect complexation of Cd to DOC. Mechanisms other than complexation
      of Cd to DOC in the intestinal lumen may therefore be involved in the inhibitory
      effect of DOC on the absorption of Cd.

PMID- 8750903
TI  - Prediction of uptake of methyl mercury by rat erythrocytes using a two
      compartment model.
AB  - The uptake of methyl mercury (MeHg) by isolated rat erythrocytes was studied at
      37 degrees C using MeHg-cysteine (MeHgCySH), MeHg-glutathione (MeHgGSH), MeHg
      mercaptalbumin (MeHgMASH) and the mixture of MeHgCySH with MeHgGSH, MeHgCySH with
      MeHgMASH, MeHgGSH with MeHgMASH at different MeHg concentrations. The measured
      MeHg concentrations were analyzed according to the Akaike's information criterion
      in order to determine the suitable compartment model. After determining a two
      compartment model, a model-independent two-compartment model was developed from
      the kinetics of uptake of MeHg at a concentration of 1 mmol MeHg/l packed
      erythrocytes using MeHgCySH, MeHgGSH and MeHgMASH, respectively. The developed
      two-compartment model was validated by predicting the kinetics of uptake of MeHg
      by rat erythrocytes at different MeHg concentrations and different mixtures of
      MeHg-complexes. Then, the predicted values were compared with the measured
      values. The results suggested: 1) MeHg uptake appeared suitable to be described
      by a two-compartment model, while using MeHgGSH, MeHgMASH, MeHgCySH at lower
      concentrations and the mixtures of MeHg-complexes; 2) MeHgCySH uptake was slowest
      among three kinds of MeHg-complexes, although a postulated cysteine-facilitated
      MeHgCySH transport system might exist in erythrocyte membrane; 3) the mixture of
      MeHg-complexes might facilitate MeHgCySH uptake; 4) there might be a second MeHg
      intracellular compartment in rat erythrocytes.

PMID- 8750904
TI  - Inhalation toxicity of diborane in rats assessed by bronchoalveolar lavage
      examination.
AB  - Changes in bronchoalveolar lavage fluid (BALF) and blood were examined to assess
      the toxic effects of diborane (B2H6, CAS: 19287-45-7) on the lung. Male Wistar
      rats were exposed to diborane at 20 ppm (intended concentration) for 4 h (phase I
      study) to evaluate time-course changes up to 14 days, and at 10 or 1 ppm
      (intended concentrations) to assess the dose-effect relationship after 3 days
      (phase II study). BALF parameters [leukocyte counts, alpha 1-antitrypsin (alpha 1
      AT), superoxide dismutase (SOD), total protein, phospholipids etc.] were examined
      and biochemical and histopathological studies were also carried out. In the phase
      I study, neutrophils (%) in BALF increased on the day of exposure and then
      decreased gradually for 3 days. Rapid and marked increases in alpha 1-AT and SOD
      activity in BALF were detected on the day of exposure, and phospholipids had
      sharply increased on day 3. After 14 days, these parameters in the exposed rats
      had returned to their background level and alpha 1-AT decreased significantly. In
      the phase II study, total protein, alpha 1-AT activity and phospholipids in BALF
      showed dose-dependent increases, and serum alpha 1-AT activity increased
      significantly. Alveolar capillary and alveolar cell damage were confirmed in rats
      exposed to 20 ppm, 10 ppm or 1 ppm diborane for 4 h by evaluating the parameters
      examined. The protection system appeared to start operating immediately after
      exposure, and the recovery mechanism seemed to start operating 1 day after
      exposure and cease by day 14. The no-observed-effect level could not be observed.

PMID- 8750905
TI  - Olfactory toxicity of methyl iodide in the rat.
AB  - The monohalomethanes (methyl iodide, methyl bromide and methyl chloride) are
      widely used industrial methylating agents with pronounced acute and chronic
      toxicity in both experimental animals and man. Recently inhalation exposure of
      rats to methyl bromide has been shown to result in severe olfactory toxicity.
      This study examined the effects on the rat nasal cavity of inhalation of methyl
      iodide (100 ppm for 0.5-6 h), and demonstrated that methyl iodide is a more
      potent olfactory toxin than methyl bromide. Within the nasal cavity the olfactory
      epithelium was the principle target tissue, and it was only at high doses (600
      ppm.h) that limited damage to transitional epithelium occurred. The squamous and
      respiratory epithelia were consistently unaffected. Within olfactory epithelium
      the sustentacular cells were the primary cellular target and damage to sensory
      cells appeared to be a secondary event. Methyl iodide induced olfactory damage
      was reversible, and 2 weeks after exposure almost complete repair had taken
      place.

PMID- 8750906
TI  - Genotoxicity of wood dust in a human embryonic lung cell line.
AB  - Wood dust exposure has been found to be an occupational hazard, being linked to
      an enhanced incidence of various neoplasias. Here we performed an experiment to
      evaluate the ability of solvent extracts of natural woods to induce chromosome
      aberrations in respiratory cells in culture. Human embryonic lung cells, MRC-5,
      grown in Dulbecco's medium were exposed to various concentrations of the dust
      extracts of pesticide-free (untreated) beech, oak and pine woods. Three
      concentrations per extract with and without metabolic activation (S9) and 100
      metaphase cells per dose were examined for possible structural aberrations.
      Although no dose-dependent activity could be found with any extract in the
      presence of S9, most aberrations observed were of the chromatid type caused by
      oak wood. Dose-dependent chromosomal breaks caused by oak and chromatid breaks
      caused by both beech and oak were observed in the absence of S9. These data might
      support the early hypothesis that hard wood dust per se contains some in vivo
      genotoxic and thus possibly carcinogenic components.

PMID- 8750907
TI  - Tissue specific basal expression of soluble murine epoxide hydrolase and effects
      of clofibrate on the mRNA levels in extrahepatic tissues and liver.
AB  - The soluble epoxide hydrolase mRNA level in liver was increased eight-fold upon
      administration of the hypolipidemic drug and peroxisome proliferator clofibrate
      for 7 days to mice. The soluble epoxide hydrolase mRNA was back at control levels
      within 1-2 days after clofibrate withdrawal. The highest expression was in liver,
      intestine and kidney. Lower levels were found in heart and muscle and very low
      levels were found in testes, lung, brain and spleen. The mRNA levels were
      increased in liver, kidney and heart by clofibrate.

PMID- 8750908
TI  - In vitro biotransformation of 2-methylpropene (isobutene) in rat lung tissue in
      comparison with liver tissue.
AB  - The epoxidation of the gaseous alkene 2-methylpropene or isobutene was studied in
      vitro in rat lung tissue in comparison with rat liver. Pulmonary tissue appears
      to be less exposed to the toxic epoxide metabolite than is the case for hepatic
      tissue. The results are correlated with the low capacity of the mixed function
      oxidase system, expressed by means of the cytochrome P-450 content and the 7
      ethoxycoumarin O-deethylase activity, to form reactive intermediates. The
      activities of the principal epoxide detoxifying enzymes glutathione S-transferase
      and epoxide hydrolase represent only 5-10% of the values measured in rat liver.

PMID- 8750909
TI  - Detection of amphetamines in fingernails: an alternative to hair analysis.
AB  - After external decontamination, the extraction of amphetamine (AP), 3,4
      methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) from
      hair and fingernails was accomplished via hot alkaline hydrolysis (1 ml 1 N NaOH,
      10 min at 95 degrees C) in the presence of deuterated internal standards,
      followed by a three-step extraction procedure. The target drugs were derivatized
      by propionylation and analyzed by GC/MS operated in the electronic impact mode.
      Results indicated that AP, MDA and MDMA were present in both hair and
      fingernails. Their concentrations, slightly higher in fingernails than in head
      hair, were 10.2 and 12.0 ng/mg for AP, 8.0 and 9.7 ng/mg for MDA and 53.4 and
      60.2 ng/mg for MDMA in head hair and in fingernails, respectively.

PMID- 8750910
TI  - Molecular diversity of cyclic nucleotide-gated cation channels.
AB  - Cyclic nucleotide-gated cation channels (CNG channels) form a multi-gene family
      consisting of at least five distinct members (CNG1-5). Expression studies have
      indicated that only CNG1-3 are able to form functional homooligomeric channels.
      Although structurally related, the cDNAs of CNG4-5 fail to induce cyclic
      nucleotide-dependent currents when expressed alone. However, when co-expressed
      with CNG1-3 they confer some of the physiologically observed properties of native
      CNG channels which are absent from the homooligomeric CNG1-3 channels. CNG
      channels are expressed in several tissues and cell types pointing to a general
      function of these channels in a wide variety of cellular systems. There is now
      increasing evidence that a major function of CNG channels may consist in
      providing a second messenger-regulated pathway for Ca2+ influx.

PMID- 8750911
TI  - G-protein-coupled receptors in normal human erythroid progenitor cells.
AB  - Human erythroid progenitor cells were isolated from peripheral blood of healthy
      donors and amplified in a suspension culture system using recombinant growth
      factors (stem cell factor, interleukin-3, granulocyte-macrophage colony
      stimulating factor and erythropoietin) as well as conditioned medium from a human
      bone marrow stroma cell line to support cell proliferation. After 6-8 days of
      culture, the cell population consisted mainly of erythroid colony-forming cells
      (burst-forming units, BFU-Es and colony-forming units, CFU-Es). In these cells,
      we studied ligand-induced changes in intracellular Ca2+ concentration ([Ca2+]i)
      and cAMP formation as the primary effector systems of guanine nucleotide-binding
      protein (G protein)-coupled receptors. The results confirmed the functional
      expression of receptors for adenosine (type A2B), prostaglandin E1 and
      isoprenaline (beta-adrenoceptor), all of which stimulated adenylyl cyclase, as
      well as for ADP (purinoceptor types P2T and P2U), platelet-activating factor and
      thrombin all of which caused a transient increase in [Ca2+]i. The efficacy of
      adenosine and prostaglandin E1 in stimulating cAMP formation was more than 5
      times higher than that of isoprenaline, suggesting a low beta-adrenoceptor
      density. The response to adenosine and isoprenaline decreased by 80 and 55%
      respectively during maturation into the proerythroblast stage. Similarly,
      thapsigargin-sensitive intracellular Ca2+ stores and ligand-induced Ca2+ release
      declined by about 60% during the CFU-E-to-erythroblast transition. The overall
      functional expression pattern of G protein-coupled receptors differed from that
      in human erythroleukaemia cell lines or from that in platelets. Primary culture
      systems for nontransformed cells, such as the one presented here, thus will be
      indispensable for the study of the functional role of G protein-dependent
      signalling during haematopoiesis.

PMID- 8750912
TI  - Crosstalk between thrombin and adenylyl cyclase-stimulating agonists in
      proliferating human erythroid progenitor cells.
AB  - Human erythroid progenitor cells grown in a suspension culture system were used
      to study possible interactions between different guanine nucleotide-binding
      protein (G-protein)-coupled receptor-effector systems during normal cell
      differentiation. Agonist-stimulated adenylyl cyclase was not inhibited by any one
      of a panel of ligands (ADP, UTP, platelet-activating factor, thrombin, alpha2
      adrenoceptor agonists, interleukin 8, lysophosphatidic acid) most of which are
      known, in other cells, to reduce cAMP formation by a Gi-mediated, pertussis toxin
      sensitive mechanism. The first four of these ligands are also known to cause
      transient changes in intracellular [Ca2+] in erythroid cells. Rather than
      inhibiting, thrombin (but not ADP, UTP or PAF) specifically caused a fivefold
      increase in the maximum adenosine- or prostaglandin E1-stimulated cAMP formation,
      without any shift of the concentration/response curves. Thrombin did not enhance
      forskolin- and AlF4-stimulated cyclase activity and had only a marginal effect on
      isoprenaline-dependent stimulation. The effect of thrombin seemed to be unrelated
      to intracellular Ca2+ release but could be partially mimicked by phorbol ester
      (PMA)-induced stimulation of protein kinase C (PKC) and was inhibited by
      staurosporin or by inactivation of PKC after long-term incubation with PMA. The
      activity of thrombin was restricted to proliferating, colony-forming progenitor
      cells while proerythroblasts were completely unresponsive. Our results suggest
      that the interaction of thrombin with Gs-linked receptors requires
      phosphorylation of a target protein that is different from adenylyl cyclase, Gs
      or Gi but may be involved in the regulation of receptor desensitization.

PMID- 8750913
TI  - Blockade of human and porcine myocardial 5-HT4 receptors by SB 203186.
AB  - We investigated the blockade of the positive inotropic effects of 5
      hydroxytryptamine (5-HT) by SB 203 186 (piperidinoethyl-indole-3-carboxylate
      hydrochloride) and its affinity for 5-HT4 receptors of human right atrium and
      piglet left atrium. We also compared the blocking effects of SB 203 186 against 5
      HT-evoked tachycardia in anaesthetised adult Yucatan minipigs as well as new-born
      Camborough piglets. SB 203 186 caused competitive antagonism of the positive
      inotropic effects of 5-HT in electrically paced atrial preparations of man (pKB =
      8.9) and piglet (pKB = 8.5) at concentrations (up to 0.3 micromol/l) which were
      devoid of depressant or stimulant effects. The affinity of SB 203 186 for atrial
      5-HT4 receptors was 30-160 times higher than that of tropisetron. 5-HT caused
      tachycardia with similar potency and efficacy in Yucatan minipigs and new-born
      Camborough piglets. SB 203 186 (0.1-3 mg/kg, i.v.) surmountably antagonised 5-HT
      evoked tachycardia in anaesthetised Yucatan minipigs or new-born Camborough
      piglets with similar potency. The blocking potency of SB 203 186 in Yucatan
      minipigs was 17 times higher than that of tropisetron. Intraduodenally
      administered SB 203 186 (0.3-3 mg/kg) to new-born Camborough piglets produced
      blockade of 5-HT-evoked tachycardia which was maximal after 20 min and lasted for
      more than 3 h with 0.3 mg/kg. The antagonism produced by the SB 203 186
      administration in new-born Camborough piglets was dose-related and threefold
      greater through the intravenous route than through the intraduodenal route. We
      conclude that SB 203 186 is an antagonist with nanomolar affinity for both human
      and porcine atrial 5-HT4 receptor. The in vivo results demonstrate that the
      sinoatrial 5-HT4 receptors function is similar in new-born Camborough piglets and
      adult Yucatan minipigs. Both porcine breeds are valid models for human atrial 5
      HT4 receptors as demonstrated with the antagonist SB 203 186.

PMID- 8750914
TI  - Mutation of two conserved arginine residues in the glucose transporter GLUT4
      supresses transport activity, but not glucose-inhibitable binding of inhibitory
      ligands.
AB  - Two arginine residues (RR333/334) in the conserved GRR motif located in the
      endofacial loop between helix 8 and 9 of the glucose transporter GLUT4 were
      substituted for leucine and alanine, respectively. Reconstituted glucose
      transport activity of the construct (GLUT4-RR333/4LA) expressed in COS-7 or LM(TK
      ) cells was less than 10% of that of the wild-type GLUT4. In contrast, binding of
      the inhibitory ligand cytochalasin B and glucose-inhibitable photolabeling with
      IAPS-forskolin were not significantly affected. Exchange of a histidine residue
      (H337Q) previously believed to be involved in the binding of inhibitory ligands
      failed to affect any of the investigated parameters. These data suggest that
      positive charges in the GRR motif at the cytoplasmic surface of the transporter
      participate in the conformational changes of the carrier protein during the
      process of facilitated diffusion.

PMID- 8750915
TI  - Lead-induced blockage of kainate-sensitive receptor channels.
AB  - The effects of bivalent lead on ion channels activated by kainate and alpha-amino
      3-hydroxy-5-methyl-4-isoxazolpropionate (AMPA) were studied using Xenopus oocytes
      microinjected with mRNA from rat brain. Lead reduced kainate-induced membrane
      currents in a reversible and dose-dependent manner, without affecting membrane
      currents induced by AMPA. Lead decreased the kainate currents with a
      concentration of 0.1 micromol/1 to 0.93 +/- 0.01 and with a concentration of 100
      micromol/1 to 0.41 +/- 0.04 of the control values. The blocking effect of lead on
      kainate responses was voltage dependent. The inhibition was strongest at -90 mV
      to -70 mV and became weaker at more positive membrane potentials. The effect of
      lead on the kainate-induced membrane currents remained unchanged when the
      concentration of kainate was increased. Hence lead probably represents a
      noncompetitive channel-blocking agent for non-N-methyl-D-aspartate (NMDA)
      receptor channels activated by kainate.

PMID- 8750916
TI  - Kainate receptors are involved in the glutamate-induced indirect, purinergic
      inhibition of [3H]-noradrenaline release in rabbit brain cortex.
AB  - Activation of ionotropic but not metabotropic glutamate receptors causes an
      indirect inhibition of the release of noradrenaline in slices of rabbit brain
      cortex. The inhibition is mediated by adenosine which activates presynaptic
      adenosine A1-receptors. The present study characterizes the ionotropic receptor
      types through which glutamate itself produces this indirect inhibition. Rabbit
      brain cortex slices were preincubated with [3H]-noradrenaline, superfused with
      medium containing desipramine (1 microM) and stimulated electrically by trains of
      6 pulses at 100 Hz. Glutamate (100-3000 micro M) reduced the electrically evoked
      overflow of tritium by up to 58%. The effect did not differ 20 min and 60 min
      after addition of glutamate. Adenosine deaminase (1 U ml-1) as well as 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX; 30 microM) and D-gamma-glutamylamino
      methanesulfonate (GAMS; 30 micro M), both of which block kainate receptors,
      attenuated the glutamate-induced inhibition. The NMDA receptor antagonist 2-amino
      5-phosphonopentanoate (AP5; 100 micro M) and the AMPA receptor antagonist 6-nitro
      7-sulfamoylbenzo(f)-quinoxaline-2,3-dione (NBQX; 30 micro M) did not change the
      effect of glutamate. Given alone, CNQX and GAMS, but not AP5 and NBQX, slightly
      increased the evoked overflow of tritium; the increases were abolished in the
      presence of adenosine deaminase. The results indicate that activation of kainate
      but not NMDA and AMPA receptors is involved in the indirect, adenosine-mediated
      inhibition by exogenous glutamate of the release of noradrenaline in rabbit brain
      cortex slices. Moreover, as shown by the increase caused by CNQX and GAMS,
      endogenous excitatory amino acids inhibit the release of noradrenaline through
      the kainate receptor-adenosine mechanism and thus contribute to the purinergic
      inhibitory control of noradrenaline release in the brain.

PMID- 8750917
TI  - Characterization of 5-hydroxytryptamine release from isolated rabbit and rat
      trachea: the role of neuroendocrine epithelia cells and mast cells.
AB  - Rabbit or rat isolated tracheae were incubated in vitro, and the release of 5
      hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA)
      was determined by HPLC with electrochemical detection. Release of 5-HT from
      rabbit tracheae could be evoked by the calcium ionophore A 23187 and, in a
      calcium-dependent manner, by depolarizing concentrations of potassium (45
      mmol/l), but not by the mast cell degranulating drug compound 48/80. High
      potassium- and A 23187-evoked release of 5-HT was markedly higher from tracheae
      of newborn compared to adult rabbits. In rabbit tracheae, mechanical removal of
      the mucosa resulted in 80-90% reduction in tissue 5-HT and in a similar reduction
      in high potassium-evoked 5-HT release. 5-Hydroxytryptophan, but not tryptophan,
      caused a marked increase in the spontaneous outflow of 5-HT and 5-HIAA from
      tracheae of newborn rabbits, and the effect on 5-HT, but not that on 5-HIAA,
      required an intact mucosa. Furthermore, treatment with 5-hydroxytryptophan caused
      an increase in tissue 5-HT and 5-HIAA, and these effects required an intact
      mucosa. In tracheae of adult rabbits 5-hydroxytryptophan caused similar, although
      less profound, effects. Adrenaline (1 micromol/1) enhanced the release of 5-HT
      from newborn rabbit tracheae, and this effect was inhibited by 1 micro mol/l
      phentolamine or 1 micromol/1 prazosin, but not affected by 100 nmol/1
      propranolol. In rat tracheae, compound 48/80 evoked a large release of 5-HT,
      whereas depolarizing concentrations of potassium (45 mmol/1) had only a very
      minor effect. In rat tracheae, 5-hydroxytryptophan had small effects on the
      outflow and tissue contents of 5-HT and 5-HIAA in comparison to the effects on
      rabbit tracheae; and removal of the mucosa resulted in only a minor reduction in
      tissue 5-HT. In conclusion, neuroendocrine epithelial (NEE) cells and mast cells
      are the major source of 5-HT in tracheae of the rabbit and rat, respectively.
      Isolated tracheae of newborn rabbits appear to be a useful model to study 5-HT
      secretion from NEE cells. 5-HT secretion from NEE cells is activated by a rise in
      intracellular calcium, and calcium influx through voltage-regulated channels
      appears to be one activating pathway. 5-HT secretion from NEE cells can be
      stimulated via alpha-adrenoceptors.

PMID- 8750918
TI  - Inhibition of pacemaker current by the bradycardic agent ZD 7288 is lost use
      dependently in sheep cardiac Purkinje fibres.
AB  - The inhibition of the pacemaker current (if) in sheep cardiac Purkinje fibers by
      ZD 7288 [4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium++  +
      chloride] is lost use-dependently. This disinhibition of if was investigated by
      using the two-microelectrode voltage-clamp technique. The pulse protocol
      consisted of a rest period (holding potential of about -50 mV, 1-10 micromol/l ZD
      7288) followed by a train of test pulses (potential negative to -100 mV,
      stimulation frequency 0.05 Hz). At the beginning of the first test pulse there
      was an immediate reduction of if but inhibition was lost during continued
      stimulation. Activation of if is sigmoidal and the early delay in current
      activation was prolonged from 33 ms (no ZD 7288) to 424 ms (10 micromol/l ZD
      7288). Therefore hardly any disinhibition occurred during short test pulses
      (0.5s). During longer test pulses (5 s, -120 mV, 10 micromol/l) disinhibition
      developed with a time constant of about 2 s. The inhibition of if by ZD 7288 was
      lost voltage-dependently. With 10 micro mol/l ZD 7288 the half-maximal
      disinhibition occurred at -92 mV and the slope factor of the
      disinhibition/voltage curve (Boltzmann relation) was 4.8 mV. The voltage
      dependent disinhibition could be abolished largely by extracellular application
      of protease (0.5 mg/ml, 7 min). After prior disinhibition, reinhibition at the
      holding potential (about -50 mV) followed a bi-exponential time course indicating
      that inhibition may be produced by a fast (tau=0.7 min) and a slow component
      (tau=20-30 min). Increasing ZD 7288 concentration from 1 to 10 mu mol/l
      accelerated reinhibition, mainly by an increase of the amplitude (A) of the fast
      component. The ratio Afast/Aslow was 0.399 at 1 micromol/l and 2.65 at 10
      micromol/l ZD 7288. The reinhibition of if was unchanged by shifting the holding
      potential from -50 mV to -20 mV. Trials to wash out the effects of 10 micromol/l
      ZD 7288 gave two results. The inhibition of if was slightly reversed after a wash
      out of 1.5 h with drug-free solution. A second effect of the drug, the fast
      reinhibition, could be completely removed by wash-out. In summary if is inhibited
      by ZD 7288 at membrane potentials at which the virtual if gate is closed.
      Disinhibition occurs during long-lasting hyperpolarization but will hardly be
      operative in unclamped fibres under physiological conditions.

PMID- 8750919
TI  - Interaction of class III antiarrhythmic drugs with muscarinic M2 and M3
      receptors: radioligand binding and functional studies.
AB  - We have recently reported that class III antiarrhythmic drugs inhibit the
      muscarinic acetylcholine (ACh) receptor-operated K+ current (IK,ACh) in guinea
      pig atrial cells by different molecular mechanisms. The data obtained from the
      patch-clamp study suggest that D,L-sotalol inhibits IK,ACh by blocking the
      muscarinic receptors, whereas MS-551 inhibits the K+ current by blocking the
      muscarinic receptors and depressing the function of the K+ channel itself and/or
      the guanine nucleotide-binding protein (G protein). This study was undertaken to
      determine whether the class III antiarrhythmic drugs D,L-sotalol and MS-551
      interact with the muscarinic receptors of cardiac and peripheral tissues. Both
      drugs inhibited concentration dependently the specific [3H]N-methylscopolamine
      ([3H]-NMS) binding to membrane preparations obtained from guinea-pig atria and
      submandibular glands. The competition curves of these drugs for [3H]-NMS binding
      to glandular membranes were monophasic, suggesting competition with [3H]-NMS at a
      single site. Although the competition curve of D,L-sotalol for [3H]-NMS binding
      to atrial membranes was monophasic, that of MS-551 was biphasic and showed high-
      and low-affinity states of binding. D,L-Sotalol showed slightly, but
      significantly, higher affinity for cardiac-type muscarinic receptors (M2) than
      for glandular-type muscarinic receptors (M3). The inhibition constant (Ki) for MS
      551 in glandular membranes was also slightly greater than the high-affinity Ki
      value for the drug in atrial membranes. In guinea-pig left atria and ilea, D,L
      sotalol shifted the concentration-response curves for the negative inotropic
      effect and the contracting effect of carbachol in a parallel manner. The slopes
      of Schild plot were not significantly different from unity, suggesting
      competitive antagonism, and the pA2 for D,L-sotalol in left atria was slightly
      greater than that in ilea. MS-551 also shifted the concentration response curve
      for the negative inotropic effect of carbachol in atrial preparations to a
      greater extent than that for the contracting effect in ileal preparations,
      although MS-551 failed to show a pure competitive antagonism. These results
      suggest that both D,L-sotalol and MS-551 interact with cardiac M2 and peripheral
      M3 receptors, and that at high concentrations they exert anticholinergic activity
      in cardiac and peripheral tissues.

PMID- 8750920
TI  - The ryanodine binding sarcoplasmic reticulum calcium release channel in
      nonfailing and in failing human myocardium.
AB  - The ryanodine-sensitive Ca2+ release channel (RyaCRC) of the sarcoplasmic
      reticulum plays a key role in the intracellular Ca2+ handling in cardiomyocytes.
      Altered expression of the RyaCRC has been supposed to contribute to abnormal
      cellular Ca2+ handling and to myocardial dysfunction in dilated and ischemic
      cardiomyopathy. In the present study the 3H-ryanodine binding site in human
      myocardial homogenates was characterized and the density of the RyaCRC (which
      corresponds to the cardiac ryanodine receptor) was determined in nonfailing and
      in failing human myocardium. Homogenates were prepared from nonfailing left
      ventricular myocardium from the hearts of 5 organ donors (NF) and from failing
      myocardium from 14 explanted hearts of transplant recipients with end-stage heart
      failure resulting from dilated (DCM, n = 5) or ischemic (ICM, n = 9)
      cardiomyopathy. Radioligand saturation binding experiments revealed a specific,
      high-affinity 3H-ryanodine binding site (Kd-values: NF: 0.65 +/- 0.11 nmol/l,
      DCM: 0.66 +/- 0.09 nmol/l, ICM: 0.88 +/- 0.18 nmol/l; n.s.) in all preparations.
      Specific 3H-ryanodine binding depended on the free Ca2+ concentration in the
      assay. It was maximal at 3-100 micro mol/l Ca2+. The binding was inhibited by the
      RyaCRC antagonists ruthenium red (Ki-value: 0.32 [0.18-0.56] micromol/l, n = 5)
      and Mg2+ (Ki-value: 2.95 [1.23-7.11] mmol/l, n = 5). The RyaCRC density was 103.5
      +/- 11.9 fmol/mg protein in nonfailing myocardium. There was no significant
      change in the RyaCRC density in dilated or ischemic cardiomyopathy (112.4 +/-
      17.1 and 122.7 +/- 13.9 fmol/mg protein) compared to nonfailing control
      myocardium. In summary, 3H-ryanodine binds specifically and with high-affinity to
      the RyaCRC in human myocardium. There is no change in the RyaCRC density in
      failing myocardium of patients with DCM or ICM in comparison to non-failing
      controls.

PMID- 8750921
TI  - Ba2+ differentially inhibits the Rb+ efflux promoting and the vasorelaxant
      effects of levcromakalim and minoxidil sulfate in rat isolated aorta.
AB  - The K+ channel openers activate ATP-sensitive K+ channels (KATP) in vascular
      smooth muscle and induce relaxation. In this study, the relationship between
      these two effects was examined in rings of rat aorta using levcromakalim and
      minoxidil sulfate as the openers and Ba2+ as the K+ channel blocker; K+ channel
      opening was assessed by determining the rate constant of 86Rb+ efflux from the
      preparation. Ba2+ inhibited the 86Rb+ efflux stimulated by levcromakalim in a
      noncompetitive manner with an IC50 value of 29 microM and a Hill-coefficient of
      1.2. At concentrations >300 microM, Ba2+ increased the tension of rat aortic
      rings concentration-dependently. Levcromakalim relaxed contractions to Ba2+ (0.5
      and 1 mM) with potencies similar to those determined against KCl (25 mM) or
      noradrenaline as spasmogens (EC50 values 15-40 nM). The vasorelaxant effect
      against Ba2+ was inhibited by the KATP channel blockers, glibenclamide and
      tedisamil, and abolished in depolarizing medium (55 mM KCl). At 3 mM Ba2+,
      levcromakalim was still able to transiently induce complete relaxation; however,
      within 1 h oscillations in tension developed, leading to a stable level of only
      15% relaxation. A similar level of relaxation was achieved against 10 mM Ba2+
      whereas the combination of 0.5 mM Ba2+ and 3 microM tedisamil blocked the
      relaxant effect of levcromakalim completely. With minoxidil sulfate as the KATP
      channel opener the results of the 86Rb+ efflux and tension experiments were
      similar to those obtained with levcromakalim. It is concluded that Ba2+ is more
      potent in inhibiting the K+ channel opening than the vasorelaxant effects of the
      openers. On the basis of the 86Rb+ efflux experiments it is estimated that at
      least 97% of the channels opened by the activators can be blocked without major
      effects on vasorelaxation suggesting a dissociation between the two effects.
      However, if the block is pushed to extremes (> or = 99.95%) the vasorelaxant
      effect of the openers is also abolished suggesting a link between both effects.
      This paradoxon remains to be solved.

PMID- 8750922
TI  - Effects of mibefradil on intracellular Ca2+ release in cultured rat cardiac
      fibroblasts and human platelets.
AB  - The Ca2+ antagonist mibefradil at supratherapeutic concentrations induced a
      sustained increase of cytosolic Ca2+ in cultured rat cardiac fibroblasts and
      human platelets which lack sensitivity to K+ depolarization and Ca2+ channel
      block by verapamil or other Ca2+ antagonists. At concentrations above 10 microM,
      mibefradil elevated substantially cytosolic [Ca2+] without affecting the peak
      level of agonist-induced Ca2+ transients. These Ca2+-mobilizing actions of 10 or
      100 microM mibefradil stand in contrast to the Ca2+ antagonism and relaxation of
      vascular muscle at 1 microM concentrations. Since a substantial part of
      mibefradil-induced increase in cytosolic Ca2+ was independent of extracellular
      Ca2+, and in order to define better the mechanism of Ca2+ increase, we exposed
      permeabilized cultured rat cardiac fibroblasts and human platelets to mibefradil
      at concentrations sufficiently high to identify covert effects. In permeabilized
      fibroblasts or platelets mibefradil at concentrations above 10 microM activated
      dose-dependent Ca2+ release from intracellular Ca2+ stores. Verapamil had no
      effect at concentrations of up to 100 microM. Mibefradil-induced Ca2+ release was
      not affected by ryanodine, thapsigargin, removal of ATP or dithioerythreitol,
      indicating that neither Ca2+ - nor disulfide reagent-induced Ca2+ release were
      involved and that mibefradil did not release Ca2+ by inhibition of the Ca2+
      ATPase pump of endoplasmic reticulum. The rate, but not the amplitude, of
      mibefradil-induced Ca2+ release is increased up to fourfold in the presence of
      pentosan polysulphate or heparin, two potent inhibitors of inositol 1,4,5
      trisphosphate-induced Ca2+ release. Depletion of Ca2+ stores of permeabilized
      cells inositol 1,4,5-trisphosphate in the presence of thapsigargin completely
      blocked mibefradil-induced Ca2+ release, and depletion of Ca2+ stores by
      mibefradil prevented further Ca2+ release by inositol 1,4,5-trisphosphate.
      Mibefradil at supratherapeutic concentrations (> or = microM) thus mobilized Ca2+
      from an inositol 1,4,5-trisphosphate-sensitive Ca2+ pool in cultured rat cardiac
      fibroblasts and human platelets.

PMID- 8750923
TI  - The inhibitory modulation of guinea-pig intestinal peristalsis caused by
      capsaicin involves calcitonin gene-related peptide and nitric oxide.
AB  - The effect of capsaicin-induced stimulation of afferent neurons on peristalsis
      and the possible neural mediators involved in this action were examined in the
      guinea-pig isolated ileum. The intraluminal pressure threshold for eliciting
      peristaltic waves was used to quantify facilitation (decrease in threshold) or
      inhibition (increase in threshold) of peristalsis. Capsaicin (0.1-1 microM)
      caused an initial short-lasting stimulation of peristalsis followed by a
      prolonged inhibition of peristaltic activity. Capsaicin (1 microM) was
      ineffective when the gut segments had been pretreated with 3.3 microM capsaicin,
      which is indicative of an afferent neuron-dependent action of the drug. In
      contrast, the abolition of peristalsis caused by a high concentration of
      capsaicin (33 microM) was fully reversible on removal and reproducible on
      readministration of capsaicin, a feature characteristic of a nonspecific
      depression of smooth muscle excitability. Baseline peristalsis and the
      excitatory/inhibitory effect of capsaicin (1 microM) on peristalsis remained
      unaltered by a combination of the tachykinin NK1 receptor antagonist (+)-(2S, 3S)
      3-(2-methoxybenzylamino)-2-phenyl piperidine (CP-99,994; 0.3 microM) and the
      tachykinin NK2 receptor antagonist (L(-)-N-methyl-N[4-acetylamino-4-phenyl
      piperidine-2-(3,4- -dichlorophenyl)butyl]-benzamide (SR-48,968; 0.1 microM).
      Further experiments, performed in the presence of a low concentration of atropine
      (10 nM) showed that the calcitonin gene-related peptide (CGRP) antagonist human
      alpha-calcitonin gene-related peptide (8-37) [hCGRP(8-37); 10 microM] attenuated
      the delayed inhibitory effect of capsaicin on peristalsis, but did not influence
      baseline peristaltic activity and the capsaicin-induced facilitation of
      peristalsis. Blockade of nitric oxide (NO) synthesis by NG-nitro-L-arginine
      methylester (L-NAME, 300 microM) facilitated baseline peristaltic activity and
      reduced the delayed inhibition of peristalsis caused by capsaicin (1 microM)
      without affecting the initial peristalsis-stimulating action of capsaicin. The
      effects of L-NAME were prevented by L-arginine (1 mM). The data of the current
      study indicate that capsaicin-sensitive afferent neurons do not participate in
      the neural pathways subserving peristalsis in the guinea-pig small intestine, but
      modulate peristaltic activity upon stimulation with capsaicin. The initial
      stimulant action of capsaicin on peristalsis is independent of tachykinins acting
      via NK1 or NK2 receptors, while the delayed capsaicin-induced depression of
      peristalsis involves CGRP and NO.

PMID- 8750924
TI  - Chronic oral nicotine administration affects the circadian rhythm of dopamine and
      5-hydroxytryptamine metabolism in the striata of mice.
AB  - The effect of chronic oral administration of nicotine on the circadian rhythm of
      striatal dopamine (DA) and 5-hydroxytryptamine (5-HT) was studied in mice. Mice
      receiving nicotine in their drinking water and control mice drinking tap water
      were killed at 05:00, 11:00, 15:00 or 21:00 hours on the 50th day of chronic
      administration. The plasma concentrations of nicotine and cotinine, as well the
      striatal concentrations of DA, 5-HT and their metabolites 3,4
      dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), homovanilic acid
      (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were estimated. The largest plasma
      concentrations of nicotine and cotinine were found at 05:00, when they were more
      than double the concentrations found at the other times studied. This indicates
      that the mice, typically for nocturnal animals, consumed most of their daily
      drinking water at night. In the control mice, the striatal DA and 3-MT
      concentrations showed circadian variation and were lowest at 11:00. The 5-HIAA
      concentrations also varied, being highest at 11:00. In the nicotine-treated mice
      the circadian variations in striatal monoamines were altered and more pronounced
      than in the controls. The concentrations of DA, DOPAC, HVA and 5-HIAA were
      highest at 11:00 and that of 5-HT at 21:00. The striatal DA, DOPAC, HVA and 5
      HIAA concentrations in the nicotine-treated mice were significantly higher at
      11:00 and the 5-HT concentrations at 21:00 than in the control mice, and, in
      contrast to the control mice, in the mice treated with chronic nicotine no
      circadian rhythm was observed in the 3-MT. No elevation of striatal DA
      metabolites occurred in the nicotine-treated mice compared with the controls when
      the plasma nicotine concentration was at its peak at 05:00. This finding suggests
      development of tolerance to the nicotine-induced changes in striatal DA
      metabolism. Further, our findings suggest that the chronic administration of
      nicotine in the drinking water of mice alters the circadian pattern of striatal
      DA and, to a lesser extent, that of 5-HT, and thus may affect the functions
      regulated by these transmitters.

PMID- 8750925
TI  - Cytochromes of the P450 2C subfamily are the major enzymes involved in the O
      demethylation of verapamil in humans.
AB  - The calcium channel blocker verapamil [2,8-bis-(3,4-dimethoxyphenyl)-6-methyl-2
      isopropyl-6-azaoctanitrile+ ++] undergoes extensive biotransformation in man. We
      have previously demonstrated cytochrome P450 (CYP) 3A4 and 1A2 to be the enzymes
      responsible for verapamil N-dealkylation (formation of D-617 [2-(3,4
      dimethoxyphenyl)-5-methylamino-2-isopropylvaleronitrile], and verapamil N
      demethylation (formation of norverapamil [2,8-bis-(3,4-dimethoxyphenyl)-2
      isopropyl-6-azaoctanitrile]), while there was no involvement of CYP3A4 and CYP1A2
      in the third initial metabolic step of verapamil, which is verapamil O
      demethylation. This pathway yields formation of D-703 [2-(4-hydroxy-3
      methoxyphenyl)-8-(3,4-dimethoxyphenyl)-6-methyl-2-isopro pyl-6-azaoctanitrile]
      and D-702 [2-(3,4-dimethoxyphenyl)-8-(4-hydroxy-3-methoxyphenyl)-6-methyl-2
      isopro pyl-6-azaoctanitrile]. The enzymes catalyzing verapamil O-demethylation
      have not been characterized so far. We have therefore identified and
      characterized the enzymes involved in verapamil O-demethylation in humans by
      using the following in vitro approaches: (I) characterization of O-demethylation
      kinetics in the presence of the microsomal fraction of human liver, (II)
      inhibition of verapamil O-demethylation by specific antibodies and selective
      inhibitors and (III) investigation of metabolite formation in microsomes obtained
      from yeast strain Saccharomyces cerevisiae W(R), that was genetically engineered
      for stable expression of human CYP2C8, 2C9 and 2C18. In human liver microsomes
      (n=4), the intrinsic clearance (CLint), as derived from the ratio of Vmax/Km, was
      significantly higher for O-demethylation to D-703 compared to formation of D-702
      following incubation with racemic verapamil (13.9 +/- 1.0 vs 2.4 +/- 0.6 ml*min
      1*g-1, mean+/-SD; p<0.05), S-verapamil (16.8 +/- 3.3 vs 2.2 +/- 1.2 ml* min-1*g
      1, p<0.05) and R-verapamil (12.1 +/- 2.9 vs 3.6 +/- 1.3 ml*min-1*g-1; p<0.05),
      thus indicating regioselectivity of verapamil O-demethylation process. The CLint
      of D-703 formation in human liver microsomes showed a modest but significant
      degree of stereoselectivity (p<0.05) with a S/R-ratio of 1.41 +/- 0.17. Anti-LKM2
      (anti-liver/kidney microsome) autoantibodies (which inhibit CYP2C9 and 2C19) and
      sulfaphenazole (a specific CYP2C9 inhibitor) reduced the maximum rate of
      formation of D-703 by 81.5 +/- 4.5% and 45%, that of D-702 by 52.7 +/- 7.5% and
      72.5%, respectively. Both D-703 and D-702 were formed by stably expressed CYP2C9
      and CYP2C18, whereas incubation with CYP2C8 selectively yielded D-703. In
      conclusion, our results show that enzymes of the CYP2C subfamily are mainly
      involved in verapamil O-demethylation. Verapamil therefore has the potential to
      interact with other drugs which inhibit or induce these enzymes.

PMID- 8750926
TI  - Bradykinin upregulates immediate-early gene mRNA in human keratinocytes.
AB  - We investigated the effect of bradykinin on the expression of the proto-oncogenes
      c-fos, c-jun and c-myc and on cell proliferation in the human keratinocyte cell
      line, HaCaT. Analysis of mRNAs was done by Northern blotting with single-stranded
      DNA hybridization probes. Bradykinin caused a rapid and transient accumulation in
      c-fos and c-jun mRNAs. In contrast, c-myc mRNA increased more slowly. Moreover,
      we report that bradykinin was a weak stimulator of HaCaT cell proliferation
      whereas epidermal growth factor, which induced the same degree of mRNA elevation,
      was shown as a powerful mitogen. Thus, while in HaCaT cells bradykinin promotes
      the expression of the proto-oncogenes c-fos, c-jun and c-myc, other biochemical
      events appear to be necessary for cell division.

PMID- 8750927
TI  - Detection of lysyl oxidase gene expression in rat skin during wound healing.
AB  - Lysyl oxidase (LOX) initiates the crosslinking of the lysine-derived aldehyde and
      plays an essential role in maturation of collagen, for example in wound healing.
      Although the activity of this enzyme has been examined in various disorders, and
      a further intriguing aspect of the relationship between LOX and tumorigenesis has
      recently emerged, its gene expression pattern in tissues is still unknown. We
      examined LOX gene expression during wound healing in rat skin. In addition, type
      III collagen gene expression was studied to determine the formation of fibrils.
      The LOX mRNA level reached a peak by day 3 after injury, which was earlier than
      that of type III collagen, and continued at a high level until day 22. The type
      III collagen mRNA level began to rise from day 3 and had increased intensely by
      day 22. In situ hybridization revealed grains corresponding to LOX mRNA in the
      fibroblasts of the granulomatous tissue. These results suggest that LOX is
      produced before collagen synthesis in preparation for crosslinking in the early
      phase of wound healing.

PMID- 8750928
TI  - Defective calcium transport in vitiliginous melanocytes.
AB  - Melanocytes were successfully established from involved and uninvolved skin of a
      patient with acute acrofacial vitiligo. Cells from involved epidermis showed a
      fivefold decrease in the rate of radiolabelled 45Ca uptake compared with
      uninvolved and control cells. These results are similar to previous findings in
      keratinocytes from involved skin in patients with vitiligo. Since 6-biopterin is
      cytotoxic to melanocytes and calcium controls the redox status of the 6
      biopterin/(6R)5, 6, 7, 8-tetrahydrobiopterin equilibrium via the thioredoxin
      reductase/thioredoxin system, these results underline the importance of this
      electron transfer system for both melanocyte function and survival.

PMID- 8750929
TI  - Increased monoamine oxidase A activity in the epidermis of patients with
      vitiligo.
AB  - Human keratinocytes under in vitro conditions synthesize norepinephrine and
      epinephrine, whereas melanocytes lack this capacity. Keratinocytes established
      from lesional and nonlesional skin of patients with vitiligo synthesized four and
      two times more norepinephrine, respectively, than controls. Epinephrine synthesis
      was similar in keratinocytes from uninvolved epidermis and controls, but cells
      from involved skin had 6.5-fold less epinephrine than controls, indicative of low
      phenylehtanolamine-N-methyl transferase (PNMT) activity. Similar results were
      obtained in five patients with vitiligo who showed low epinephrine levels in
      involved epidermis. Both human keratinocytes and melanocytes expressed
      significant levels of monoamine oxidase A (MAO-A) activities as shown using 14C
      labelled 5-hydroxytryptamine as substrate and immunohistochemical staining with
      mouse monoclonal antibody. MAO-A activities in the total epidermis of patients
      with vitiligo were increased five- to ten-fold compared with skin of type-matched
      controls. Similar increases in MAO-A activities were also found in both
      keratinocytes and melanocytes established in vitro from vitiliginous epidermis.
      Based on these results, it can be concluded that defective catecholamine
      synthesis in the epidermis of patients with vitiligo leads to increased levels of
      norepinephrine with a concomitant increase in MAO-A activity.

PMID- 8750930
TI  - Immunoreactive analogues of erythrocyte ankyrin in human epidermal keratinocytes.
AB  - Using immunoblot and immunofluorescence analysis, we demonstrated the presence
      and localization of an immunoreactive form of erythrocyte ankyrin in human
      epidermal keratinocytes. Immunoblot analysis revealed that both human epidermis
      and cultured epidermal keratinocytes contained ankyrin-like proteins of molecular
      mass 210 kDa that crossreacted with antihuman erythrocyte ankyrin antibodies.
      Immunofluorescence microscopy revealed that the plasma membrane of epidermal
      keratinocytes was stained. Eccrine sweat gland cells and ductal cells were also
      stained. These results indicate that in human epidermal keratinocytes, eccrine
      sweat gland cells and ductal cells, an ankyrin-like protein is present as one of
      the membrane proteins. The present findings and our recent previous studies
      showing the presence of a spectrin-like protein (fodrin) and 4.1-like proteins in
      these cells enable us to suggest that a membrane skeletal protein lattice may
      exist in these cells.

PMID- 8750931
TI  - Protein kinase C-dependent modulation of stimulatory guanine nucleotide binding
      protein of fetal rat skin keratinocytes.
AB  - Although the protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate
      (PMA) has been known to induce heterologous desensitization of the epidermal
      adenylate cyclase, the precise mechanism of PMA action remains unknown. Effects
      of PMA on the receptor-G-protein-adenylate cyclase system of fetal rat skin
      keratinocytes (FRSK) were investigated. Choleratoxin catalysed the ADP
      ribosylation of 45 kDa and 52 kDa membrane proteins and islet activating protein
      (IAP) catalysed the ADP ribosylation of a 40 kDa membrane protein. Incubation of
      FRSK with PMA decreased the cholera toxin-catalysed ADP ribosylation of the
      membrane protein, but not the IAP-catalysed ADP ribosylation. The effect of PMA
      on the cholera toxin-catalysed ADP ribosylation was inhibited by the PKC
      inhibitor, H-7 (1-(5-isoquinolinesulfonyl)-2-methyl piperazine dihydrochloride).
      1-Oleoyl-2-acetylglycerol (OAG), a membrane-permeable diacylglycerol analogue,
      also decreased the cholera toxin-catalysed ADP ribosylation, but 4-0-methyl PMA,
      a very weak PKC activator, had no effect. Keratinocytes are known to express the
      guanine nucleotide binding proteins, Gsalpha, Gi2alpha, and Gi3alpha. Immunoblot
      analysis of the PMA-treated FRSK showed no detectable difference in the amount of
      Gsalpha, Gi2alpha, Gi3alpha, or the beta subunit of the G-protein. PMA
      significantly decreased the beta-adrenergic adenylate cyclase response and
      cholera toxin-induced cyclic AMP accumulation, while it markedly increased
      forskolin-induced cyclic AMP accumulation. These results indicate that phorbol
      esters affect the stimulatory guanine nucleotide binding protein (Gs) of FRSK via
      a PKC-dependent pathway.

PMID- 8750932
TI  - Proliferation and differentiation of cultured human follicular keratinocytes are
      not influenced by biotin.
AB  - In humans and in animals, biotin deficiency causes pathological changes in the
      skin and its appendages. High doses of biotin may also have beneficial effects on
      skin, hair and fingernails in humans and animals with normal biotin status.
      Therefore, we investigated the effects of low and high concentrations of biotin
      on proliferation and differentiation of cultured outer root sheath cells from
      human hair follicles as an in vitro model for skin. The activities of biotin
      dependent carboxylases were measured to evaluate the biotin status of the cells.
      In monolayer cultures of outer root sheath cells, proliferation and expression of
      the differentiation-specific keratins K1 and K10 were not influenced by extremely
      low concentrations of biotin (<2 x 10(-10) mol/l) or by pharmacological doses of
      biotin (10(-5) mol/l). Biotin deficiency of the cells was confirmed under the
      former condition by demonstrating decreased activities of the mitochondrial
      carboxylases. In organotypic cocultures of outer root sheath cells and dermal
      fibroblasts, in which stratified epithelia resembling epidermis were developed,
      the biotin concentration had no effect on the expression of all tested epidermal
      differentiation markers, including the suprabasal keratins K1 and K10, the
      hyperproliferation-associated keratin K16, involucrin and filaggrin.

PMID- 8750933
TI  - The effects of ultraviolet A and reactive oxygen species on the mRNA expression
      of 72-kDa type IV collagenase and its tissue inhibitor in cultured human dermal
      fibroblasts.
AB  - The effects of ultraviolet A (UVA) radiation and reactive oxygen species (ROS),
      generated with a xanthine and xanthine oxidase (XOD) system, on collagen
      enzymatic degradation involving the matrix metalloproteinase (MMP) and its tissue
      inhibitor of metalloproteinase (TIMP) were investigated using cultured human
      dermal fibroblasts. Total RNA was isolated and subjected to Northern blot
      analysis using cDNA clones for human interstitial collagenase (MMP-1), 72-kDa
      type IV collagenase (MMP-2) and TIMP-2. UVA irradiation resulted in an increase
      in MMP-1 mRNA up to 2.3-fold, but did not stimulate MMP-2 or TIMP-2 mRNA
      expression. In contrast, ROS induced by the xanthine and XOD system resulted in a
      dose-related increase in the level of MMP-2 mRNA up to 2.1-fold and a decrease in
      the level of TIMP-2 mRNA by 49% in the same fibroblasts. Catalase, used as
      scavenger, essentially prevented the ROS-induced alterations in MMP-2 and TIMP-2
      mRNA levels. These results suggest that ROS produced in the dermis may contribute
      to biological changes in the connective tissue matrix observed in photoaging skin
      by accelerating the MMP-2-related matrix degradation system.

PMID- 8750934
TI  - Sparfloxacin phototoxicity: potential photoaugmentation by ultraviolet A and B
      sources.
AB  - Sparfloxacin, a quinolone antibacterial agent, frequently elicits photosensitive
      skin reactions. Our clinical studies of patients treated with sparfloxacin have
      demonstrated that this photosensitivity is primarily phototoxic and that a marked
      erythematous response is induced by sequential irradiation with ultraviolet A
      (UVA) and B (UVB) but not UVA or UVB alone, suggesting potential synergism
      between UVA and UVB. We evaluated the phototoxicity of this agent using in vitro
      DNA breaking activity and in vivo murine cutaneous responses. Sparfloxacin
      induced DNA strand breaks in vitro and converted the supercoiled closed circular
      form of plasmid DNA to the open circular form by its photodynamic action. In
      mice, the topical application of sparfloxacin and subsequent irradiation with
      UVB, but not UVA, induced ear swelling responses. However, the UVB-induced ear
      swelling response was augmented by irradiation with UVA before or after UVB
      exposure. Such interaction between UVA and UVB in the production of ear swelling
      was further confirmed by systemic administration of sparfloxacin. Our study
      suggests that sparfloxacin is a unique phototoxic agent in that photosensitivity
      dermatitis is evoked by photoaugmentation between UVA and UVB.

PMID- 8750935
TI  - Plasma membrane fluidity of keratinocytes of normal and psoriatic skin: a study
      using fluorescence anisotropy of trimethylammoniumdiphenylhexatriene (TMA-DPH).
AB  - The aim of this study was to investigate plasma membrane fluidity in human
      keratinocytes using fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene
      (DPH) and its cationic derivative 1-[4-(trimethylamino)-phenyl]-6-phenyl-1,3,5
      hexatriene (TMA-DPH). Keratinocytes from normal or psoriatic skin were isolated
      using trypsin-EDTA or dispase. In keratinocytes isolated from normal skin, TMA
      DPH anisotropy values were higher than those observed using DPH; the difference
      must be related to the different localization of the two probes. In fact, DPH in
      whole cells localizes in plasma as well as intracellular membranes, yielding an
      average value of fluidity, while the cationic derivative TMA-DPH resides in the
      plasma membrane of the whole cells for a sufficient time for anisotropy
      measurements. Moreover, it has to be considered that plasma membrane is more
      ordered than intracellular membranes. The kinetics of incorporation of TMA-DPH
      was similar in keratinocytes isolated using trypsin-EDTA and those isolated
      using; dispase, however, the fluorescence anisotropy values were lower in
      keratinocytes isolated with dispase (0.260 +/- 0.01 vs 0.270 +/- 0.01, p =
      0.029). This difference is probably related to modifications of lipid-protein
      interactions after trypsin treatment. Since no damage to plasma membrane after
      incubation with dispase seems to have been reported, we decided to use this
      separation procedure to study plasma membrane fluidity in psoriasis, a human
      pathological condition characterized by excessive cell proliferation and
      incomplete differentiation. Lower anisotropy values (0.260 +/- 0.01 vs 0.270 +/-
      0.01, p = 0.001), indicating an increase in fluidity, were observed in
      keratinocytes isolated from skin of psoriatic patients than in epidermal cells
      isolated from normal human skin. We suggest that the measurement of fluorescence
      anisotropy in living cells is a convenient and useful tool to study membrane
      fluidity in human keratinocytes isolated from normal and diseased skin. Its
      application represents a technical advance because plasma membrane fluidity can
      be measured using very limited amounts of tissue, as obtained from biopsies.

PMID- 8750936
TI  - The role of nitric oxide in carotid chemoreception.
AB  - Immunocytochemical and histochemical studies of cat and rat carotid bodies have
      revealed a plexus of nitric oxide synthase (NOS)-positive nerve fibers associated
      with lobules of chemosensory type I cells as well as with the carotid body
      vasculature. NOS-positive fibers originate from (1) autonomic neurons located in
      the carotid body and distributed along the carotid sinus nerve (CNS) and IXth
      cranial nerve which terminate in the adventitial layer of carotid body blood
      vessels, and (2) from unipolar sensory neurons of the petrosal (IXth nerve)
      ganglion. Carotid bodies incubated with the NO precursor, 3H-arginine, yield 3H
      citrulline, the detectable coproduct of NO synthesis. Furthermore, electrical
      stimulation of the CNS or exposure of carotid bodies to hypoxic incubation media
      elevates 3H-citrulline formation. Millimolar concentrations of L-arginine inhibit
      chemoreceptor activity evoked by hypoxia, an effect which is reversed by the
      specific NOS antagonist, L-NG-nitroarginine methylester (L-NAME, 0.1 mM).
      Electrical stimulation of CNS C fibers elevates cyclic GMP in the carotid body
      vasculature and lobules of type I cells. Cyclic GMP production is reduced during
      stimulation in the presence of L-NAME, a finding consistent with the known
      ability of NO to activate a soluble form of guanylate cyclase. Further studies
      showed that brief (< 1 min) stimulation of CNS C fibers inhibits basal
      chemoreceptor discharge in a perfused/superfused in vitro carotid body
      preparation, whereas prolonged (> 5 min) stimulation is required to inhibit the
      response to hypoxia. The inhibitory effect is reversed by L-NAME. Our combined
      anatomical, neuropharmacological and electrophysiological data suggest that NO
      plays a dual role in mediating CNS inhibition, one via its actions on the organ's
      vasculature and the other through direct effects on the chemosensory type I
      cells. The former pathway involves cholinergic/NOS presumptive parasympathetic
      autonomic neurons, while the latter may be mediated by axon reflex or primary
      affarent depolarization of chemosensory nerve terminals.

PMID- 8750937
TI  - c-fos expression as a marker of central cardiovascular neurons.
AB  - Immunohistochemical detection of Fos, the protein product of the immediate-early
      gene c-fos, was evaluated as a functional marker of central neurons sensitive to
      a change of blood pressure/blood volume. Controlled hemorrhage and infusion of
      the hypotensive agent nitroprusside or hydralazine induced the appearance of Fos
      immunoreactivity (Fos-IR) in several prominent groups of central neurons: the
      piriform cortex, bed nucleus of the stria terminalis, islands of Calleja,
      subfornical organ, central nucleus of the amygdala, parabrachial nucleus,
      supraoptic and paraventricular nuclei, pontine A5, locus ceruleus, ventrolateral
      medulla, the nucleus of the solitary tract, area postrema, and intermediolateral
      cell column in the spinal cord. Elevation of blood pressure by infusion of
      phenylephrine caused the appearance of Fos-IR in fewer groups of neurons: the bed
      nucleus of the stria terminalis, central nucleus of the amygdala, parabrachial
      nucleus, the nucleus of the solitary tract and area postrema. The differential
      distribution of Fos neurons in hypotensive versus hypertensive animals
      underscores the potential application of Fos as a metabolic marker in identifying
      a network of neurons responding to a specific cardiovascular challenge. Further,
      simultaneous characterization of the transmitter phenotype of Fos-containing
      neurons offers an additional advantage of this method over other conventional
      tract-tracing techniques.

PMID- 8750938
TI  - Role of acetylcholine, corticoids and opioids in the rostral ventrolateral
      medulla in stress-induced hypertensive rats.
AB  - Hypertension was induced in Sprague-Dawley and Wistar rats by irregular foot
      shocks combined with a buzzing noise for 2 h twice a day for 1-2 weeks. The
      plasma catecholamine, corticosterone, angiotensin II, glucose and lipids were
      found to increase in parallel. The acetylcholine (ACh) and choline
      acetyltransferase in rostral ventrolateral medulla (rVLM) increased markedly).
      Microinjection of ACh or cholinergic agonists into rVLM induced a pressor effect,
      and microinjection of M receptor blockers had a depressor effect.
      Electrophysiological studies showed that the stress-induced hypertension was
      closely related to the activation of a cholinergic system in rVLM. Microinjection
      of corticoids into rVLM had led to a pressor response which could be blocked by
      Ru38486, spironolactone, cholinergic blockers or verapamil. Microinjection of
      morphine and mu- or delta-receptor agonists into rVLM caused bradycardia and a
      reduction of arterial pressure that could be blocked by naloxone.

PMID- 8750939
TI  - Relationship of rostral ventrolateral medullary neurons and angiotensin in the
      central control of blood pressure.
AB  - The rostral ventrolateral medulla (RVL) in the medulla oblongata contains a group
      of vasomotor neurons that regulate the level of arterial blood pressure. That
      these spinal-projecting neurons were spontaneously active, cardiac-locked and
      barosensitive further underlies their important role in generating a tonic
      sympathoexcitatory outflow. In pentobarbital anesthetized spontaneously
      hypertensive rats (SHR), the electrophysiological behaviours of these
      sympathoexcitatory cardiovascular neurons were significantly different from those
      of normotensive Wistar Kyoto rats (WKY). In SHR, there was an equal occurrence of
      slow-conducting single discharge units and fast-conducting double discharge units
      while the vast majority of RVL neurons was single discharge units in WKY.
      Further, the single discharge units of SHR had a higher firing rate and a more
      regular discharge pattern than those in WKY. The activity of a subpopulation of
      these RVL cardiovascular neurons was excited by iontophoretic application of
      angiotensin II, with the magnitude and duration of the excitation greater in SHR
      than in WKY. Besides, microinjection of [Sar1, Ile8]-angiotensin II, an
      angiotensin II antagonist, to RVL caused a greater decrease in the firing rate of
      a subpopulation of RVL cardiovascular neurons in SHR than in WKY. In both types
      of rats, the neuronal responses were significantly greater in double discharge
      units than in single discharge units. This was followed by a subsequent depressor
      response which was significantly greater in SHR than in WKY. These observations
      demonstrate that in SHR the altered spontaneous electrophysiological property of
      sympathoexcitatory neurons in the RVL and their augmented sensitivity to the
      tonic influence of brain angiotensin may contribute to the manifestation of
      hypertension in this strain of rats.

PMID- 8750940
TI  - Cardiovascular function of the paraventricular nucleus of the hypothalamus.
AB  - Recent evidence is showing that the paraventricular nucleus (PVN) of the
      hypothalamus plays a key role in autonomic regulation. Studies by the author of
      the PVN neurones that project to the spinal cord are reviewed. These neurones are
      inhibited by arterial baroreceptors and excited or inhibited by pulmonary/cardiac
      vagal afferents. Volume load or low dose atrionatriuretic peptide can stimulate
      vagal afferents to excite PVN-spinal neurones. Ibotenic acid-induced lesions of
      PVN-spinal neurones abolish a reflex increase in renal vascular conductance
      following volume load. This effect appears to be independent of the PVN
      vasopressin or oxytocin-containing neurones which directly excite spinal
      sympathetic neurones. It is suggested that different chemically coded PVN-spinal
      neurones produce differential effects on spinal cardiovascular neurones, either
      monosynaptically or via interneurones.

PMID- 8750941
TI  - beta-Adrenoceptors in endothelium of rabbit coronary artery and alteration in
      atherosclerosis.
AB  - The existence of beta-adrenoceptor (beta-AR) in endothelium of rabbit coronary
      artery and its alteration in atherosclerosis (AS) were determined by relaxation
      experiments in isolated preparations and in situ hybridization with a digoxigenin
      labelled beta 2-AR cDNA probe. The concentration-relaxing response curves for
      isoproterenol (ISO) and norepinephrine (NE) in the presence of phentolamine were
      shifted to the right, and the maximal relaxations were reduced by removing the
      endothelium. Nitric oxide synthase inhibitor L-NG-nitro-arginine reduced the
      maximal relaxation induced by ISO, while the cyclooxygenase inhibitor
      indomethacin showed no effect on relaxation. In situ hybridization showed that
      mRNA for beta-AR was detected not only in smooth muscles, but also in endothelial
      cells. Coronary artery AS was created by high cholesterol feeding and was
      confirmed histologically under light microscopy. The relaxation response to
      acetylcholine (ACh) was abolished or significantly diminished in AS preparations.
      The relaxation responses to ISO or NE, however, were potentiated in AS arteries,
      especially in those which showed diminished (but not abolished) ACh response. The
      relaxation induced by sodium nitroprusside was reduced significantly in the AS
      arteries. Those results suggest that beta-AR are present in endothelium of rabbit
      coronary artery, and that endothelium beta-AR-mediated vasorelaxation is
      potentiated in AS.

PMID- 8750942
TI  - A revisitation on the mechanism of action of KCl-induced vascular smooth muscle
      contraction: a key role of cation binding to the plasma membrane.
AB  - Aortic rings of Sprague-Dawley rats developed reproducible contractions in Ca
      free, nominally Mg-free (2 microM), Na-free, K solution, but not in Ca-free,
      nominally Mg-free, K-free, Na solution. Further reduction of the residual Mg by
      0.5 mM EDTA in the above solutions potentiated this K-induced contraction and
      allowed the development of a relatively small contraction in Na-rich medium,
      respectively. The amplitude of EDTA-enhanced, K-induced contraction was almost
      the same as the amplitude of contraction induced in K-rich ([K] = 142 mM), Ca
      containing (2.5 mM) solution. Such K-induced contraction was completely inhibited
      by 38 mM Na and by 3 mM of Mg (and Ni or Cd). Nifedipine (1 microM) also
      inhibited aortic smooth muscle contraction produced in K-EDTA, Ca-free solution.
      Modulators of Ca in sarcoplasmic reticulum (ryanodine, caffeine and
      norephinephrine), Ca-ionophore (A-23187) and protein kinase C inhibitor
      (Calphostin C) had no effect on EDTA-enhanced, K-induced contraction. It was
      suggested that K-induced contraction in rat aorta is not dependent on the
      increase in cytosolic Ca following membrane depolarization, is not a result of
      the release of Ca from intracellular stores, and is not due to change of Ca
      sensitivity upon the activation of protein kinase C. We propose that the
      competition of K for Mg and Na at external binding sites on the plasma membranes
      of the smooth muscle cells is primarily responsible for the development of
      vascular contraction.

PMID- 8750943
TI  - The role of intracellular pH in the control of adenosine output from red skeletal
      muscle.
AB  - More than 30 years ago, it was proposed that adenosine was released from skeletal
      muscle in response to a decrease in the oxygen supply-to-demand ratio. It has
      subsequently been confirmed that adenosine is released from red muscles in
      proportion to the contraction frequency, but the mechanism that controls its
      release remains controversial. There is no direct evidence for the involvement of
      oxygen insufficiency in the process, and there is some indirect evidence that it
      is not involved. On the other hand, there is direct evidence that a decrease in
      pH, with no change in oxygen supply-to-demand ratio, can stimulate adenosine
      release, and the amounts of adenosine released are well correlated with the pH
      change in all situations tested. A direct analysis of the role of hypoxia in
      adenosine release is therefore urgently needed.

PMID- 8750944
TI  - Signal transduction in the cardiac k-receptor.
AB  - The presence of k-binding sites in the heart suggests a regulatory role of k
      receptor in the cardiac functions. Recent studies have provided evidence that
      activation of cardiac k-receptor elevates intracellular free calcium ([Ca2+]i) by
      increasing mobilization of calcium from the intracellular store. The mobilization
      of intracellular calcium results from an increased production of inositol-1,4,5
      trisphosphate (IP3). The increase in [Ca2+]i may manifest in cardiac arrhythmias
      while the depletion of calcium from the intracellular store may reduce the
      contractility elicited upon depolarization. The responses of IP3/[Ca2+]i are
      significantly attenuated after development of tolerance to k-opioids due mainly
      to the impairment of postreceptor events. The attenuated responses of IP3/[Ca2+]i
      to k-receptor activation may be responsible for the failure of the k-agonists to
      induce cardiac arrhythmias and to reduce electrically induced calcium transients
      in the ventricular myocytes.

PMID- 8750945
TI  - The role of the autonomic nerves in the control of nasal circulation.
AB  - Patients suffering from allergic or vasomotor rhinitis usually show nasal mucosal
      hyperaemia, engorgement, hyperrhinorrhoea and obstruction of the nasal airway.
      The nasal mucosa is drained by two venous systems which are anatomically and
      functionally separate. The nasal mucosa receives tone discharges from the
      sympathetic nerves but not from the parasympathetic nerves. Sympathetic nerve
      stimulation causes constriction of the resistance vessels via the alpha
      adrenergic mechanism and constriction of the capacitance vessels via the alpha
      adrenergic mechanism and some non-adrenergic and non-cholinergic mechanism; the
      capacitance vessels are under more prominent sympathetic influence than the
      resistance vessels. Parasympathetic nerve stimulation causes non-cholinergic
      dilatation of both resistance and capacitance vessels; dilatation is more
      pronounced in the posterior venous system. Simultaneous optimal stimulation of
      the autonomic nerves resulted in vasoconstriction, especially of the capacitance
      vessels. Hence, nasal congestion may be related more to a withdrawal of
      sympathetic discharge than to an overactivity of the parasympathetic nerves.

PMID- 8750946
TI  - Hemodynamic mechanisms of neurogenic pulmonary edema.
AB  - Acute lung injury has been reported in man and animals with intracranial
      disorders, head trauma or cerebral compression. Early studies in our laboratory
      demonstrated that pulmonary hemorrhagic edema (PHE) of acute and fulminating type
      occurred accompanying severe hypertension and bradycardia (Cushing responses) in
      animals following cerebral compression (CC) or intracranial hypertension (ICH).
      The lung pathology was prevented by spinal transection and sympathoadrenergic
      blocking agents, but was not affected by decerebration, adrenalectomy, vagotomy
      and atropine. The effects of central sympathetic activation due to ICH on the
      systemic and pulmonary resistance and capacitance vessels were studied in dogs
      with a total heart bypass preparation. ICH caused an increase in vascular
      resistance with a reduction in the vascular capacity of the systemic and
      pulmonary circulation. The relative importance of hemodynamic changes was further
      analyzed with the measurement of aortic and pulmonary flows and the use of right
      and left heart bypass. The overall pattern of imbalance in the right and left
      cardiac output was characterized by an immediate fall in aortic flow accompanying
      a slower decline in pulmonary arterial flow. In rats with a right heart bypass,
      ICH produced severe pulmonary venous hypertension and PHE. In the left heart
      bypassed rats, ICH induced systemic hypertension, whereas no significant changes
      occurred in the lungs. Our studies reveal that: (1) ICH elicits vasoconstriction
      of the systemic and pulmonary resistance and capacitance vessels and (2) the
      major cause of volume and pressure loading in the pulmonary circulation is acute
      left ventricular failure resulting in a dramatic decrease in aortic flow.

PMID- 8750947
TI  - Imaging of childhood torticollis due to atlanto-axial rotatory fixation.
AB  - Atlanto-axial rotatory fixation is a rare cause of childhood torticollis. It may
      occur spontaneously or may be associated with trauma, upper respiratory tract
      infection or congenital abnormality of the cervical spine. Presentation is
      usually with persistent torticollis and "cock robin" deformity of the neck. In
      this paper the radiological experience in three patients is presented.
      Investigations included plain radiographs, plain anteroposterior tomography, CT
      and MRI. Displacement of the lateral mass of the atlas and the eccentric position
      of the odontoid peg can be seen in the plain films. CT scan can exclude fractures
      and confirm atlanto-axial rotation. The superimposition of CT images is
      demonstrated as a way of diagnosing subluxation. MRI offers better soft tissue
      differentiation and allows assessment of the integrity of the transverse
      ligament. This has an important bearing on the prognosis and may influence
      surgical treatment. It is important to recognise the plain film features of this
      uncommon condition and confirm the diagnosis with CT or MRI. The treatment
      options are discussed with particular reference to long term outcome.

PMID- 8750948
TI  - EEG, PET, SPET and MRI in intractable childhood epilepsies: possible surgical
      correlations.
AB  - Magnetic resonance imaging (MRI), single photon emission tomography (SPET), and
      positron emission tomography (PET) using [18F]fluorodeoxyglucose were used in
      combination with scalp and scalp-video EEGs in a group of 30 pediatric patients
      with drug resistant epilepsy (DRE) in order to identify patients who could
      benefit from neurosurgical approach. Seizures were classified according to the
      consensus criteria of The International League Against Epilepsy. In three
      patients infantile spasms (IS) were diagnosed; 13 subjects were affected by
      different types of generalized seizures, associated with complex partial seizures
      (CPS) in three. In the other 14 patients partial seizures, either simple (SPS) or
      complex, were present. A localized abnormality was demonstrated in one patient
      with IS and in three patients with generalized seizures. Of the group of 14
      subjects with CPS, MRI and CT were normal in 7, but SPET or PET indicated focal
      hypoperfusion or hypometabolism concordant with the localization of the EEG
      abnormalities. In 5 of the other 7 patients anatomical and functional imaging and
      EEG findings were concordant for a localized abnormality. It can be concluded
      that functional imaging combined with scalp EEGs appears to be superior to the
      use of only CT and MRI for selecting children with epilepsy in whom a surgical
      approach can be considered, in particular when CPS resistant to therapy are
      present.

PMID- 8750949
TI  - Cerebral hydatid cyst in children. Experience of 27 cases.
AB  - The authors present 27 cases of cerebral hydatid cyst (CHCy) treated between 1980
      and 1992. These cases of CHCy represent 2.8% of all cases of expansive
      nontraumatic lesions in children. Most of the patients were between 6 and 10
      years of age. There was a substantial prevalence of male patients-18 cases
      (66.6%). Most of the children with CHCy were from rural areas. The cysts were all
      located in the cerebral hemispheres (none in the posterior fossa). Usually two or
      three lobes were affected and the cysts were most often retrorolandic. Only 8
      patients (29.6%) also had pulmonary or hepatic infestation. All patients were
      operated on immediately the diagnosis was established. Operative mortality was
      very low (1 patient died immediately after surgery). There have been 11 cases of
      recurrence; all these patients have been reoperated on. Neurological sequelae
      were mainly partial and general seizures. Epilepsy developed postoperatively in
      five patients. Paresis, which usually disappears in time, was the most common
      motor disturbance. Two other important postoperative complications were subdural
      effusion and ventricular dilatation (six cases). There have been five cases of
      multiple recurrences (four of these patients have since died). Treatment with
      albendazole was used in three cases without significant results.

PMID- 8750950
TI  - Chronic ("normal pressure") hydrocephalus in childhood and adolescence. A review
      of 16 cases and reappraisal of the syndrome.
AB  - "Normal pressure" hydrocephalus (NPH) is generally considered to be a disorder of
      the adult and geriatric population. Only a few reports have described the
      possible occurrence of this condition in children. A series of 16 patients aged
      less than 20 years forms the basis of the present report. Among these 16
      patients, 11 had a clearly identified etiologic factor and 7 had had a shunt
      previously implanted. The majority of patients exhibited at least two elements of
      the adult's triad of psychomotor retardation (14 cases) and/or psychotic-like
      symptoms (4 cases), gait anomalies (8 cases), and sphincter disturbances (3
      cases). Six patients had their intracranial pressure (ICP) monitored. ICP values
      were estimated to be within the normal limits for age. All the 16 patients
      underwent shunting or shunt revision. Surgical results were as follows (mean
      follow-up 20 +/- 17.2 months): a good response to shunting was obtained in 12
      cases ("cured": 5, improved: 7), while the other 4 patients failed to improve. It
      seems likely that associated parenchymal disorders have played a major role in
      therapeutic failures. In children showing ventricular dilation on computed
      tomographic (CT) analysis and a clinical picture of subtle psychomotor
      deterioration, it may be difficult to distinguish an active disorder of the CSF
      dynamics from "arrested hydrocephalus." Since intracranial manometry cannot be
      undertaken as a routine procedure, less invasive methods such as cerebrospinal
      fluid (CSF) tap test, psychometric, or urodynamic tests deserve special attention
      as reliable predictors of outcome after shunting. Because most patients undergo
      shunting without prior assessment of their CSF pressure, the term "chronic
      hydrocephalus" is proposed as an alternative designation to "NPH," since there is
      little argument for maintaining an instrumentally based definition of the
      syndrome.

PMID- 8750951
TI  - Cranial burst fracture in infants: acute recognition and management.
AB  - In the past, the diagnosis of "growing skull fracture" or "diastatic fracture"
      has included a subset of injuries better referred to as "cranial burst fracture."
      Cranial burst fracture, typically associated with severe injury in infants less
      than 1 year of age, is a closed, widely diastatic skull fracture accompanied by
      acute cerebral extrusion outside the calvarium. We treated 11 such infants at the
      LeBonheur Children's Medical Center and 2 at the Children's National Medical
      Center from January 1986 through December 1994. Infants ranged in age from 1 to
      17 months, with an average age of 5.7 months. All presented with marked scalp
      swelling and a Glasgow Coma Scale score of 10 or less. Twelve had a history
      consistent with severe injury (motor vehicle accident, 7, abuse 5). The cause of
      injury in one patient remains unproven. Surgery (reduction of herniated cerebral
      tissue, repair of large dural laceration, and cranioplasty) was usually performed
      within 10 days of injury, a time period long enough to assure hemodynamic
      stability and resolution of acute cerebral swelling, yet sufficiently brief to
      avoid the chronic changes (scarring, parasitization of scalp vessels by damaged
      cortex) associated with a "growing skull fracture." Prompt repair of cranial
      burst fracture may prevent ongoing brain injury such as has been
      neuropathologically demonstrated in patients with "growing skull fracture."
      Magnetic resonance imaging establishes the diagnosis of cranial burst fracture in
      equivocal cases, rendering unnecessary a "waiting period" to see if scalp
      swelling resolves. Our experience, together with information in the
      neuropathological and neurosurgical literature, suggests that cranial burst
      fracture is associated with severe trauma, requires expeditious treatment, and
      has been underdiagnosed in the past, leading to "growing skull fracture," a
      condition requiring more extensive surgery.

PMID- 8750952
TI  - Symptomatic intracranial hemorrhage in full-term infants.
AB  - A retrospective analysis was undertaken in a consecutive series of 33 full-term
      infants (birth weight > 2500 g and a minimum of 37 weeks gestational age) with
      symptomatic intracranial hemorrhage (ICH) admitted to a regional neonatal
      intensive care unit from January 1986 to December 1992. Eleven infants were born
      in our institution; 17 were male. The estimated local incidence of symptomatic
      ICH for the inborn population was 4.9/10000 live births, with a regional
      incidence of 2.7/10000 live births. Twenty-four (72.3%) infants presented with
      seizures, apnea, or respiratory distress. Five (15.1%) children developed ICH
      associated with extracorporeal membrane oxygenation, ventriculoperitoneal
      shunting, and cardiac surgery. There were two deaths (6.1%) associated with a
      grade IV periventricular hemorrhage (PVH) and cardiac surgery. Nine infants
      (27.3%) showed PVH, while an additional nine children developed multifocal
      cortical hemorrhages. Eight infants (24.2%) showed extra-axial ICH, four children
      (12.1%) sustained lobar hemorrhages, and three children (9.1%) showed ICH
      associated with prenatal CNS abnormalities. Excluding five children with
      iatrogenic ICH, coagulopathies occurred in 9 of 28 infants (32.1%) and
      constituted a major determinant of the development of ICH. Neurosurgical
      intervention was limited to one infant with massive ICH and one child with
      hydrocephalus as a late sequela of ICH. Developmental follow-up was complete in
      32 children with a mean and median duration of 3.4 years. Full-term infants with
      ICH associated with risk factors for hypoxic-ischemic injury showed a
      significantly greater risk of developmental delay compared to infants with
      uncomplicated ICH.

PMID- 8750953
TI  - Syringohydromyelia as a complication of Goldenhar syndrome.
AB  - Goldenhar syndrome is a multifocal developmental disorder consisting of ocular,
      auricular and vertebral anomalies. A case of Goldenhar syndrome is presented with
      a previously undescribed association with syringohydromelia. The pertinent
      literature is reviewed and possible mechanisms of the pathogenesis of
      syringohydromyelia in this syndrome are discussed.

PMID- 8750954
TI  - Hyponatremia in central partial diabetes insipidus due to postoperative
      hypothalamic tumor.
AB  - We report the case of a 4-year-old boy with a postoperative hypothalamic tumor,
      who exhibited unusual water and electrolyte disturbance. This developed as a late
      manifestation during the course of central diabetes insipidus (DI), which started
      when the patient was 2 years old. Clinically, hyponatremia and DI appeared
      alternately within 1 day. The hyponatremia (lowest value Na+ 115 mmol/I) was
      associated with afebrile convulsions. Assessment of fluid status revealed that
      the patient had a reduced capacity for arginine vasopressin(AVP) secretion
      (partial DI), which was not physiologically regulated and which was not
      concomitantly sufficient to produce maximally concentrated urine and allow the
      production of maximally diluted urine. This defective osmoreceptor function in
      association with the previously existing reduced capacity for AVP release seemed
      to be responsible for the fluid disturbance in the patient. The administration of
      nasal 1-desamino-8D-arginine vasopressin (DDAVP) only when urine output was
      increased, instead of regular administration at a fixed time, prevented both
      worsening of hyponatremia and development of DI.

PMID- 8750955
TI  - Effect of inhibin, follistatin, or activin infusion into the lateral hypothalamus
      on operant behavior of rats fed lysine deficient diet.
AB  - To identify brain mechanisms which mediate hunger for amino acid (e.g. L-lysine;
      Lys) deficiency, rats were trained to bar press (FR30 schedule) to receive 50 mg
      pellets of a complete diet. Rats given a lysine deficient (Lys-def) diet ad
      libitum maintained a high rate of bar pressing but when allowed ad libitum access
      to 0.4 M Lys to drink had a significant decrease in pressing. Also, Lys
      continuously infused by minipump into the lateral hypothalamic area (LHA)
      inhibits pressing by rats given a Lys-def diet. The threshold maximal dose is
      between 0.1-0.5 nmol Lys/h. Therefore, animals lacking dietary Lys will work to
      receive complete diet, but replacement of Lys by voluntary consumption or by
      direct infusion into the LHA inhibits bar pressing for complete diet. The ratio
      of brain activin and inhibin may modulate motivation to work for a complete diet,
      since continuous inhibin or follistatin, but not activin, infusion into the LHA
      was found to inhibit bar pressing, which is normally quite strong in rats
      maintained on Lys-def diet. The inhibitory effect of LHA inhibin infusion was
      replicated, and concurrent availability of Lys solution ad libitum was additive
      with LHA inhibin infusion to depress responding further. This inhibitory effect
      of inhibin or follistatin did not result from altered ad lib. consumption of Lys
      def diet. Although LHA Lys infusion did decrease consumption of a concurrently
      available Lys solution, inhibin did not change ad libitum Lys consumption. This
      indicates that inhibin may work in the LHA to inhibit bar pressing for complete
      diet via other mechanisms than sensation of Lys deficiency.

PMID- 8750956
TI  - Pharmacologic characterization of refilling inositol 1,4,5-trisphosphate
      sensitive Ca2+ stores in NG108-15 cells.
AB  - Following mobilization with the inositol 1,4,5-trisphosphate (IP3)-generating
      agonist bradykinin, Ca2+ stores in neuroblastoma x glioma hybrid, NG108-15 cells
      require extracellular Ca2+ to refill. The process by which this store refills
      with Ca2+ was characterized by recording bradykinin-induced intracellular free
      Ca2+ concentration transients as an index of the degree of refilling of the
      store. Cyclopiazonic acid, a microsomal Ca2+ ATPase inhibitor, reversibly
      depleted intracellular Ca2+ stores in these cells, but did not recruit detectable
      Ca2+ influx, suggesting that these cells lack substantial capacitative Ca2+
      entry. The paucity of voltage-sensitive Ca2+ channels in undifferentiated NG108
      15 cells, suggested that a channel analogous to that proposed to mediate
      capacitative Ca2+ entry in nonexcitable cells might assist refilling IP3
      sensitive Ca2+ stores in these cells. The possibility that compounds shown
      previously to inhibit capacitative Ca2+ entry in nonexcitable cells might inhibit
      the refilling of the IP3-sensitive store in NG108-15 cells was explored. The IP3
      sensitive store was depleted by exposure to bradykinin, allowed to refill briefly
      in the presence of the test compound and then challenged again with bradykinin to
      evaluate the degree of refilling of the store. The imidazole derivatives,
      econazole (10 microM), L-651582 (10 microM) and SKF 96365 (20 microM), all
      completely blocked the bradykinin-induced Ca2+ response. Calmodulin antagonists,
      W-7 (100 microM) and trifluoperazine (10 microM), were also effective, although
      at concentrations well above those required to inhibit calmodulin. Because of the
      high concentrations required to inhibit bradykinin responses, the possibility
      that these agents might have additional effects was explored. Compounds were
      tested in a paradigm in which the store was preloaded with Ca2+ before treatment.
      All of these agents depleted, at least partially, the preloaded store. Econazole
      was the least effective of the compounds tested for releasing stores, although it
      was comparable to the other compounds for inhibition of refilling. Although NG108
      15 cells refill intracellular Ca2+ stores by a plasmalemmal Ca2+ leak, this leak
      shares a pharmacology similar to the capacitative Ca2+ entry pathway described
      for nonexcitable cells.

PMID- 8750957
TI  - Membrane-mediated inhibition of corticosterone on the release of arginine
      vasopressin from rat hypothalamic slices.
AB  - The arginine vasopressin (AVP) released from the hypothalamic slices containing
      paraventricular and supraoptic nuclei of Sprague-Dawley rats sectioned with
      vibratome and incubated in static microchambers was measured by radioimmunoassay.
      The effect of bovine serum albumin-conjugated corticosterone (B-BSA) on the AVP
      release was investigated. The results were as follows: (1) B-BSA, within 20 min,
      significantly inhibited AVP release in a dose-dependent manner from 10(-7) to 10(
      4) mol/l. (2) RU38486 (10(-4)-10(-3) mol/l) could partially block the inhibitory
      effect of B-BSA although it by itself did not change the AVP release. (3) With
      the elevation of Ca2+ concentration in the incubation medium, the AVP release was
      increased and the inhibitory effect of B-BSA enhanced; while in the absence of
      Ca2+, the AVP release decreased and the effect of B-BSA attenuated. (4) The
      inhibitory effect of B-BSA was enhanced in the presence of neomycin which itself
      had no influence on AVP release. These results indicated that the inhibitory
      effect of corticosterone is rapid and membrane-mediated which is non-genomic
      rather than classical genomic, and that the extracellular Ca2+ play a role in
      this rapid inhibitory effect.

PMID- 8750958
TI  - Tubulin stimulates adenylyl cyclase activity in rat striatal membranes via
      transfer of guanine nucleotide to Gs protein.
AB  - Previous studies of rat cerebral cortex and rat C6 glioma cells have demonstrated
      that dimeric tubulin is capable of activating the G proteins Gs and Gil via
      transfer of guanine nucleotide from tubulin to Gs alpha and Gil alpha. To provide
      further information regarding cytoskeletal modulation of adenylyl cyclase, the
      present study examined effects of tubulin on the activation of the enzyme in rat
      striatal membranes. Tubulin, prepared from rat brain by polymerization with the
      hydrolysis-resistant GTP analog 5'-guanylylimidodiphosphate (GppNHp) caused
      significant activation of adenylyl cyclase by approximately 130%. Furthermore,
      tubulin-GppNHp activated SKF 38393-sensitive adenylyl cyclase and potentiated
      forskolin-stimulated activity of the enzyme. When tubulin, polymerized with the
      hydrolysis-resistant photoaffinity GTP analog [32p]p3 (4-azidoanilido)-p1-5'-GTP
      ([32P]AAGTP), was incubated with striatal membranes, AAGTP was transferred from
      tubulin to Gs alpha as well as Gi alpha with the extents of nucleotide transfers
      being 7.6 +/- 0.8% and 17.8 +/- 1.4% of AAGTP originally bound to tubulin,
      respectively. These results indicate that, in rat striatum, the tubulin dimer
      participates in the stimulatory regulation of adenylyl cyclase by transferring
      guanine nucleotide to Gs alpha, supporting the hypothesis that tubulin
      contributes to the regulation of neuronal signal transduction.

PMID- 8750959
TI  - Role of calcium in sigma-mediated neuroprotection in rat primary cortical
      neurons.
AB  - Since unique calcium dynamics have been reported for toxic (40-80 M) and non
      toxic (5-10 microM) concentrations of glutamate, we evaluated the effect of
      neuroprotective sigma ligands on glutamate and potassium chloride (KCl)
      stimulated changes in [Ca2+]i using 12-15 day old primary rat neuronal cortical
      cultures. In approximately 80% of the neurons tested, 80 microM glutamate caused
      a sustained calcium flux previously shown to be associated with neurotoxicity.
      The majority of sigma ligands that were evaluated altered glutamate-induced
      calcium flux. For example, the primary effect of maximally neuroprotective
      concentrations of the sigma ligands dextromethorphan, (+)-pentazocine, (+)
      cyclazocine, (+)-SKF 10047, carbetapentane and haloperidol was a shift from a
      sustained, to either a biphasic or a monophasic transient calcium response
      indicative of neuroprotection. (+)-3-PPP, previously shown not to be
      neuroprotective in this model system, failed to alter glutamate-induced calcium
      flux. In contrast to glutamate, KCl (50 mM) produced changes in [Ca2+]i which
      were not neurotoxic to the neurons as measured by LDH release. The primary
      response observed in 59% of the neurons treated with 50 mM KCl alone was an
      initial spike in [Ca2+]i which abruptly declined then plateaued above basal
      levels throughout the 12 min of analysis (modified sustained response). The
      highly selective sigma ligands produced a shift from the modified sustained
      response to a monophasic transient calcium response. Again, (+)-3-PPP had no
      effect on KCl-induced calcium dynamics. Of the PCP-related sigma ligands only (+)
      SKF-10047 consistently attenuated the KCl-induced calcium flux. Collectively,
      these results indicate that modulation of [Ca2+]i through receptor and voltage
      gated calcium channels contributes significantly to sigma mediated
      neuroprotection.

PMID- 8750960
TI  - Release of excitatory and inhibitory amino acids from the locus coeruleus of
      conscious rats by cardiovascular stimuli and various forms of acute stress.
AB  - The release of amino acids in the locus coeruleus (LC) of conscious, freely
      moving rats was studied in time periods of 3 min by use of push-pull superfusion
      under basal conditions and during application of various experimental stimuli
      known to influence the activity of the LC-noradrenergic system. Tail pinch for 3
      min led immediately to a pronounced tetrodotoxin-sensitive increase in the
      release rates of the excitatory amino acids (EAA) glutamate (Glu) and aspartate
      (Asp) and to moderate increases in GABA and taurine (Tau) outflow. Immobilization
      stress for 9 min elevated the release of the EAA Glu and Asp, as well as that of
      the inhibitory amino acid GABA to a similar extent. A fall of blood pressure (BP)
      by nitroprusside or haemorrhage slightly enhanced the release rates of Glu and
      Asp. Noradrenaline-induced rise in BP, as well as hypervolaemia increased the
      release rate of GABA, but did not influence the release rates of Glu, Asp, Tau
      and arginine (Arg). The results provide direct evidence that the amino acid
      release pattern in the LC of conscious rats differs in response to various
      stimuli, according to the modality of the stimulus. A functional significance of
      excitatory and inhibitory amino acids in the regulation of LC activity during
      stress and haemodynamic changes is suggested.

PMID- 8750961
TI  - Aromatic L-amino acid decarboxylase immunoreactive cells in the rat striatum: a
      possible site for the conversion of exogenous L-DOPA to dopamine.
AB  - The efficacy of L-dihydroxyphenylalanine (L-DOPA) in ameliorating the symptoms of
      Parkinson's disease (PD) is attributed to its conversion to dopamine (DA) by the
      enzyme aromatic L-amino-acid decarboxylase (AADC) in the striatum. Although the
      site of this conversion in the DA-denervated striatum has yet to be identified,
      it has been proposed that L-DOPA could be converted to DA at non-dopaminergic
      sites containing AADC. In the present study, we used immunocytochemical
      techniques to examine the localization of AADC and DA in the striatum of rats
      with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal
      dopaminergic projection. In the DA-denervated striatum, we observed AADC
      immunoreactive (-IR) cells with morphological characteristics similar to a class
      of small aspiny interneuron. Although usually obscured by a dense plexus of AADC
      IR fibers, these cells could also occasionally be detected in the intact
      striatum. Acute administration of L-DOPA to DA-denervated animals elicited
      contralateral rotational behavior as well as a pronounced c-fos protein
      immunoreactivity in the striatum ipsilateral to the lesion. Following acute
      administration of L-DOPA, but not after acute saline, DA-IR cells were detected
      in the denervated striatum. These DA-IR cells are similar in morphology and were
      found in the same location as the AADC-IR cells. These results strongly suggest
      the existence of a class of AADC-containing striatal cells that can form DA from
      exogenous L-DOPA in the rat. In the DA deafferented striatum, DA produced by
      these cells from exogenous L-DOPA could be released to exert physiological
      effects on DA receptive tissue. It is possible that similar cells could
      contribute to the efficacy of L-DOPA in the treatment of Parkinson's disease.

PMID- 8750962
TI  - Role of nitric oxide, adenosine, N-methyl-D-aspartate receptors, and neuronal
      activation in hypoxia-induced pial arteriolar dilation in rats.
AB  - In this study, we tested the hypothesis that nitric oxide (NO) and adenosine
      (ADO) are the principal mediators of severe hypoxia-induced vasodilation. In
      addition, we examined whether activation of N-methyl-D-aspartate (NMDA) receptors
      and/or perivascular nerves plays a role. A closed cranial window and intravital
      microscopy system was used to monitor diameter changes in pial arterioles
      (approximately 40 microns) in anesthetized rats. The relative contributions of
      ADO, NMDA, NO, and neuronal activation to hypoxic cerebrovasodilation were
      assessed using the blockers 8-sulfophenyltheophylline (8-SPT), MK-801, nitro-L
      arginine methylester (L-NAME), and tetrodotoxin (TTX). Two experimental series
      were studied. In the first, we tested the effects of NOS inhibition, via topical
      L-NAME (1 mM), on moderate (PaO2 approximately 46 mmHg) then severe (PaO2
      approximately 34 mmHg) hypoxia-induced dilation. To confirm that L-NAME was
      affecting specifically NO-dependent responses, we also examined, in each
      experiment, the vasodilatory responses to topical applications of NOS-dependent
      (adenosine diphosphate (ADP); acetylcholine (ACh)) and -independent (sodium
      nitroprusside (SNP)) agents, in the presence of L-NAME or, in controls, the
      presence of D-NAME or no added analogue. In the second series, topical suffusions
      of ADP, ADO, and NMDA were sequentially applied, followed by 5 min exposure to
      severe hypoxia (PaO2 approximately 32 mmHg). Following return to normoxia, a
      suffusion of either 8-SPT (10 microM), MK-801 (10 microM), TTX (1 microM), or 8
      SPT+MK-801 was initiated (or, in controls, application of a drug-free suffusate
      was maintained), and the above sequence repeated. In control, TTX, and 8-SPT+MK
      801 experiments, baseline conditions were then restored and hypercapnia (PaCO2 =
      70-85 mmHg) was imposed. In the series 1 control groups, moderate and severe
      hypoxia elicited approximately 20% and 35-40% increases in diameter,
      respectively. L-NAME attenuated ADP- and ACh-induced dilations, did not alter the
      arteriolar responses to SNP or moderate hypoxia, but prevented further dilation
      upon imposition of severe hypoxia. This suggested that 45-50% of the severe
      hypoxia response was NO-dependent. In series 2, 8-SPT blocked the adenosine
      response and reduced severe hypoxia-induced dilation by 46%. MK-801 predictably
      blocked NMDA-induced relaxation and reduced the hypoxic response by 42%. When
      combined, 8-SPT and MK-801 affected hypoxic vasodilation additively. After TTX,
      the ADP and ADO responses were normal, but NMDA and hypoxia responses were
      completely blocked. Hypercapnia-induced dilation was unaffected by TTX or 8
      SPT+MK-801. The results imply that severe hypoxia-induced release of NO and ADO,
      and the accompanying pial arteriolar dilation, are wholly dependent on the
      capacity to generate action potentials in perivascular nerves. The similarity of
      the L-NAME and MK-801 effects on hypoxic cerebrovasodilation suggests that the NO
      dependency, to a large degree, derives from NMDA receptor activation.

PMID- 8750963
TI  - Significant changes in neuropeptide concentrations in the brain of normotensive
      (WKY) and spontaneously hypertensive (SHR) rats following knee joint
      monoarthritis.
AB  - Changes induced by chronic monoarthritis in the nervous system was studied by
      measuring concentrations of substance P (SP)-, neurokinin A (NKA)-, calcitonin
      gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivities in
      the brain and in the knee joints of control and monoarthritic normotensive (WKY)
      and spontaneously hypertensive (SHR) rats on day 21 after the induction of
      monoarthritis. Knee joint monoarthritis was induced by intra-articular injection
      of Freund's adjuvant into the right knee joint. The severity of arthritis was
      examined by measuring knee volumes and scratching behaviour and by X-ray. The
      right knee of both WKY and SHR monoarthritic rats had an increased volume and
      osteoporosis. SHR rats had more severe arthritis and increased scratching
      behaviour compared to the WKY. Tachykinins were significantly decreased in the
      hypothalamus of arthritic rats. In the pituitary higher concentrations of
      tachykinins and CGRP were found in the arthritic and/or control SHR rats than in
      the WKY. In the occipital cortex, striatum and hippocampus NPY was increased in
      monoarthritic rats. No correlation was found between neuropeptide concentrations
      in the brain and knee joints. Decrease of tachykinins and increase of CGRP to
      different degree in the hypothalamus and/or pituitary of the arthritic WKY and
      SHR rats indicates that these changes were selectively associated with the basal
      level of sympathetic tone and possibly related to the greater severity seen in
      SHR rats. The increase of NPY in the brain, not influenced by sympathetic tone,
      may be part of a general defence reaction to inflammation.

PMID- 8750964
TI  - Evidence to support the peripheral branching of primary afferent C-fibres in the
      rat: an in vitro intracellular electrophysiological study.
AB  - Intracellular voltage recordings were made in vitro at 36.5 +/- 1 degrees C from
      35 rat lumbar dorsal root ganglion (DRG) neurones with a peripheral conduction
      velocity (CV) in the C-fibre range (0.3-2.2 m/s). The peripheral nerve (PN) was
      stimulated in one of three different ways, each delivering single stimuli (0.1-1
      ms duration, 2-3-times threshold; maximum 50 V) at a low frequency (0.3 Hz). With
      each of the three stimulation methods used here a similar proportion of cells
      (approximately 30%) showed changes, either an abrupt latency change or a soma
      invasion by two action potentials (APs). Both of these changes were consistent
      with branching of primary afferent C-fibres in the PN.

PMID- 8750966
TI  - T-cell costimulatory molecules B7-1 (CD80) and B7-2 (CD86) are expressed in human
      microglia but not in astrocytes in culture.
AB  - The B7-1 and B7-2 expressed on the 'professional' antigen-presenting cells (APC)
      of the lymphoid system are counterreceptors for the T cell antigens CD28/CTLA-4.
      The B7/CD28 interaction provides a critical costimulatory signal in the decision
      between functional activation or clonal anergy of T cells. To investigate the
      biological role of B7 in the central nervous system, constitutive and cytokine
      induced expression of B7 was investigated in fetal human astrocytes and microglia
      in culture. B7-1 expression was minimally detectable in unstimulated microglia
      but was increased markedly following exposure to IFN-gamma or GM-CSF. B7-2 was
      expressed at a high level in untreated microglia and upregulated to a small
      degree by exposure to IFN-gamma or GM-CSF. In contrast, B7-1 and B7-2 were
      undetectable in astrocytes under unstimulated or IFN-gamma/GM-CSF-treated
      conditions. These results indicate that both B7-1 and B7-2 are expressed in
      cultured human microglia but not in astrocytes.

PMID- 8750965
TI  - Differential effects of hexachlorocyclohexane isomers on the GABA receptor
      chloride channel complex in rat dorsal root ganglion neurons.
AB  - The GABAA receptor-chloride channel complex has recently been demonstrated by
      patch clamp experiments to be the target of cyclodiene insecticides. We have now
      examined the effects of four isomers of hexachlorocyclohexane (HCH), alpha-, beta
      , gamma- and delta-HCH, on the GABAA receptor-chloride channel complex of rat
      dorsal root ganglion neurons using patch clamp techniques. When co-applied with
      10 microM GABA, 1 microM gamma-HCH slightly enhanced and then suppressed the GABA
      induced chloride current. The desensitization of the current was greatly
      accelerated by gamma-HCH in a dose-dependent manner. The acceleration of
      desensitization and the suppression of sustained component of current by gamma
      HCH occurred at lower concentration ranges than those for the suppression of peak
      current. When 10 microM delta-HCH was co-applied with 10 microM GABA, current was
      greatly enhanced and then suppressed, and the level of enhancement was much
      higher than that of gamma-HCH. alpha- and beta-HCH had little or no effect on the
      GABA-induced chloride current. The differential actions of these isomers on GABA
      activated chloride currents account for variable symptoms of poisoning in insects
      and mammals.

PMID- 8750967
TI  - Synergistic action of corticosterone on kainic acid-induced electrophysiological
      alterations in the hippocampus.
AB  - The present study investigates the effect of overexposure to high doses of the
      stress hormone corticosterone (CORT) on the electrophysiological changes produced
      in the hippocampus after local microinjection of KA. Extracellular recordings
      were performed in the CA1 area of mouse hippocampal slices prepared after a 7-day
      recovery period following KA microinfusion alone or combined with 3 days
      overexposure to CORT. The results showed that CORT shifts the KA response profile
      approximately 40-fold, since animals treated with a non-toxic dose of 0.01
      microgram KA and CORT exhibited epileptic activity and a shift on the paired
      pulse response similar to that observed in animals treated with high doses of KA
      (0.4 microgram). This synergistic action of CORT on the electrophysiological
      changes induced by KA was antagonized by the antiglucocorticoid RU486 whereas the
      antimineralocorticoid spironolactone was ineffective. These results suggest that
      CORT may play an important role in modulating the severity of KA-induced seizures
      in the hippocampal structure probably by GR-receptor mediated action.

PMID- 8750968
TI  - Hypertensive effect of tissue kallikrein in rostral ventrolateral medulla is
      mediated by brain kinins.
AB  - Microinjections of kallikrein, 0.5-2.0 units, in the rostral ventrolateral
      medulla (RVLM) of brain increased arterial pressure in Wistar-Kyoto (WKY) and
      spontaneously hypertensive rats (SHR). This effect was significantly greater in
      SHR. The kinin B2 receptor antagonist icatibant (Hoe 140) blocked the
      hypertensive responses to kallikrein in both groups and caused greater
      hypotension and bradycardia in SHR. These results suggest that local kinins in
      the RVLM act to alter cardiovascular function and may be involved in the
      maintenance of blood pressure in the SHR.

PMID- 8750969
TI  - Chronic cerebral hypoperfusion in the rat: temporal delineation of effects and
      the in vitro ischemic threshold.
AB  - Acute reductions in cerebral blood flow of up to 50% do not affect neuronal
      function although it has been shown that reductions of a similar magnitude
      maintained for 26 weeks do induce neuronal changes. In vitro rat hippocampal LTP
      was evaluated after 10 weeks of cerebral hypoperfusion. An assessment was also
      made of the possible 'robustness' of hippocampal CA1 pyramidal neurons to
      combined in vitro hypoxic/ischemic insults because of previously shown
      differences in hemodynamic autoregulatory curves. No differences were found
      between controlled and chronically hypoperfused animals in either study. It is
      concluded that the changes in neuronal function induced by reductions in cerebral
      blood flow of less than 50% take time to develop and do not induce adaptive
      changes in affected neurons. The mechanism for these changes remains to be
      elucidated.

PMID- 8750970
TI  - Glia-dependent neurotoxicity and neuroprotection in mesencephalic cultures.
AB  - Dopaminergic neurotoxicities of 6-hydroxydopamine (6-OHDA) and the
      lipopolysaccharide (LPS) were compared in rat mesencephalic cultures plated on
      poly-L-lysine or on glial monolayers. In the neuron-enriched cultures plated on
      polylysine, 6-OHDA killed 89% of the tyrosine hydroxylase (TH)-immunopositive
      neurons, but LPS was not neurotoxic. Conversely, in mixed neuron/glial cultures,
      6-OHDA killed only 27% of the TH-immunopositive neurons while LPS killed 70%. The
      mixed neuronal/glial mesencephalic culture offers a better in vitro model for
      studying possible mechanisms involved in Parkinson's disease.

PMID- 8750971
TI  - Inhibition of purified (Na+,K+)-ATPase activity from porcine cerebral cortex by
      NO generating drugs.
AB  - We tested the effects of several nitric oxide (NO) generating compounds on the
      activity of sodium-potassium adenosine 5'-triphosphatase [(Na+,K+)-ATPase]
      purified from porcine cerebral cortex. Sodium nitroprusside (SNP), S-nitroso-N
      acetylpenicillamine (SNAP), 3-morpholinosydnonimine (SIN-1) and (d1)-(E)-ethyl-2
      [(E)-hydroxyimino]-5-nitro-3-hexeneamide (NOR 3) inhibited the (Na+,K+)-ATPase
      activity dose dependently. Superoxide dismutase, a NO scavenger, and sulfhydryl
      (SH) compounds, reduced-form glutathione (rGSH) and dithiothreitol (DTT),
      prevented the inhibitory action of SNAP, SIN-1 and NOR 3 but not of SNP, when
      applied simultaneously with NO generating compounds, and this enzyme inhibition
      could be reactivated by the incubation with these SH compounds but not with SOD.
      The inhibitory action by SNP was magnified by simultaneous application of DTT.
      These results suggest that NO generating compounds, SNAP, SIN-1 and NOR 3 but not
      SNP, may release NO or NO-derived products and may inhibit (Na+,K+)-ATPase
      activity by interacting with a SH group at the active site of the enzyme.

PMID- 8750972
TI  - TrkA, TrkB and p75 mRNA expression is developmentally regulated in the rat
      retina.
AB  - We examined the cellular distribution of mRNAs coding for the neurotrophin
      receptors TrkA, TrkB and p75 in the rat retina during early postnatal
      development. At P0 (postnatal day 0), mRNAs coding for each of the three
      receptors were detected in the ganglion cell layer (GCL) and in the inner
      plexiform layer (IPL), the latter structure essentially containing retinal
      ganglion cell processes at this developmental stage. At P5, the innermost part of
      the inner nuclear layer (INL) also expressed TrkA, TrkB and p75 mRNAs. Finally,
      the GCL, IPL and the whole INL of P10 retinae were labeled by the three probes.
      The developmentally regulated expression of these receptors underlies a possible
      role for neurotrophins in the differentiation and survival of retinal cells.

PMID- 8750973
TI  - Molecular diversity of GABA-gated chloride channels in the rat anterior
      pituitary.
AB  - mRNA expression of GABA-gated Cl(-)-channels in rat antepituitary was evaluated
      by using an reverse-transcribed (RT)-polymerase chain reaction (RT-PCR) method
      with degenerate and specific oligonucleotides. The main result of our findings is
      that the antepituitary expresses mRNAs encoding alpha 4 and rho 1 GABA receptor
      subunits. These two subunits are believed to be, respectively, constituents of
      benzodiazepine-insensitive GABAA and GABAC receptors in the CNS. This molecular
      analysis is consistent with the pharmacological diversity of GABA receptors in
      pituitary cells.

PMID- 8750974
TI  - The vestibular nuclei of the rat project to the lateral part of the thalamic
      parafascicular nucleus (centromedian nucleus in primates).
AB  - To clarify the vestibular projections to the centromedian-parafascicular nuclear
      complex, the Phaseolus vulgaris leucoagglutinin (PHA-L) and horseradish
      peroxidase conjugated to wheat germ agglutinin (WGA-HRP), tracing studies have
      been done in rats. The data demonstrated that the lateral parafasicular nucleus
      received vestibular afferents mainly from the ventral part of medial vestibular
      nucleus, and the superior and inferior vestibular nuclei, with an ipsilateral
      predominance. These findings suggest the vestibular influence to the motor loop
      of the basal ganglia thalamocortical projections.

PMID- 8750975
TI  - Endocytosis of aminoglycoside antibiotics in sensory hair cells.
AB  - Immuno-gold electron microscopy was used to assess the uptake pathways of
      aminoglycoside antibiotic kanamycin (KM) in sensory hair cells. Accumulation of
      gold particles was evident on the plasma membrane as well as in large smooth
      vesicles beneath the apical surfaces of hair cells 12 h after a systemic
      administration of KM. Immuno-gold was exclusively localized in the vesicles 27 h
      post-injection. Cationic ferritin, a membrane-bound insoluble marker, was
      colocalized with KM in the vesicle structures after their simultaneous in vitro
      application. These results strongly suggest that KM is taken up into sensory hair
      cells via receptor-mediated endocytosis at their apical surfaces. In addition,
      the profound time lag between KM uptake and hair cell death suggests involvement
      of targeting mechanisms in cytotoxic signalling pathways of the drugs.

PMID- 8750976
TI  - Sympathetically-mediated cardiovascular responses induced by neurochemical
      microinjection in the brainstem lateral tegmental field of cat.
AB  - This study examines sympathetically-mediated cardiovascular responses arising
      from microinjections of AMPA and kynurenic acid in the medullary lateral
      tegmental field (LTF). The resulting behavior, which is predominantly inhibitory,
      is nearly identical to that reported for the para-ambiguual area lying just
      lateral to the LTF, and suggests that the two regions may share other
      cardiovascular control functions.

PMID- 8750977
TI  - Changes in expression of NR-1 and c-jun mRNA in rat lumbar spinal cord after
      neonatal common peroneal nerve crush.
AB  - We have examined the expression of the NR-1 subunit of the glutamate NMDA
      receptor and the immediate early gene c-jun in lumbar spinal cord following
      neonatal common peroneal nerve crush. The expression of these two genes was
      studied up to 12 days post-injury (crush occurring at neonatal day P2). The
      levels of both NR-1 and c-jun mRNA were increased in spinal cord ipsilateral to
      the site of crush, the induction of mRNA was shown to occur in a time-dependent
      manner, peaking at 5 days post-injury. The level of NR-1 mRNA showed the most
      substantial change following nerve crush, increasing 5 times from 4 h to 5 days
      post-crush. An increase in expression of NR-1 was also observed in spinal cord
      contralateral to the injury, although quantitatively this was a smaller effect.
      These results indicate that early postnatal injury causes a significant increase
      in the expression of NR-1 mRNA which is most marked at 5 days after injury. This
      period coincides with that of maximum cell death and indicates that the selective
      induction of NR-1 could underlie the mechanism of this cell death.

PMID- 8750978
TI  - [Gerontology and an aging population. Reduction in fundamental research].

PMID- 8750979
TI  - [Tardive dyskinesia: an increased risk of neuroleptics in elderly women].
AB  - Tardive dyskinesia is a side-effect of antipsychotic drugs. Elderly women with
      depression are at risk even on a low dosis. A case is presented in which a
      typical depression was treated with high dosis haloperidol resulting in orofacial
      dyskinesia and a less frequently seen grunting. Correct diagnosis, indication,
      dosis monitoring and regular evaluation of possible side-effects are the most
      important factors to prevent these serious invalidating conditions.

PMID- 8750980
TI  - [Standardized behavior assessment plays a minor role in arriving at indications
      for admission to a psychogeriatric nursing home].
AB  - To investigate the role which standardised, patient related data play in
      indicated admission to a psychogeriatric nursing home, we compared the data of
      120 indicated with those of 68 not-indicated patients. High scores on subscales
      'helplessness' and 'inactivity' of the Dutch version of the Stockton Geriatric
      Rating Scale were the best predictors of indicated admission to a certain extent
      (21.6%). Furthermore a history of cardiac diseases and the state of being
      unmarried increased the probability of indicated admission to a small degree.
      Only a limited percentage of the variance in the decision of the indication
      committee could be explained. The limited availability of data which are
      collected in a standardised way, especially data concerning the caregiving system
      and the absence of valid and reliable instruments for the investigation of
      indicated admission are the most probable causes of this fact.

PMID- 8750981
TI  - [Effectiveness of validation. A literature study].
AB  - This review-article reports on literature on the effectiveness of validation; and
      approach used for disoriented elderly. Literature has been searched for by means
      of several (computerized) indexes and references. By contacting Feil, who
      developed validation, unpublished articles and reports became available. This
      search resulted in 13 effect-studies, of which 7 are unpublished, 2 descriptive
      reports, and 1 research-proposal. The effect-studies have varying designs with
      different methodological restrictions causing bias. The analysis showed that the
      quality and therefore the evidential value of the effect-studies is limited. The
      better the study, the less validation appeared to be effective. It is concluded
      that the hypothesis, that validation has positive effects on disoriented elderly
      and their caregivers, has no or minimal scientific basis. Before validation is
      implemented more and more in Dutch health care, scientific research addressing
      its effects is indicated.

PMID- 8750982
TI  - [Perceived stress caused by informal caregiving. Construction of a scale].
AB  - We hypothesize that 'self-perceived pressure from informal care' is an important
      result of the appraisal process of caregivers. This pressure refers to the
      demands of the caregiving situation in comparison with the personal interests of
      the caregiver. For the measurement of this 'Self-Perceived Pressure from Informal
      Care' of informal caregivers of demented elderly (N = 167) a 9-item Rasch scale
      (SPPIC) was developed with a satisfying Index of Subject Separation (.66) and
      reliability (Rho = .79). Findings revealed that 'Self-Perceived Pressure from
      Informal Care' is one dimension which varies from less to more pressure.
      Perceived pressure did not differ for male and female caregivers, and for spouse
      and non-spouse caregivers. The associations of perceived pressure with the
      psychological and psychosocial complaints of the caregivers and with the
      stressors in the caregiving situation support the validity of the SPPIC (Pearson
      r = .26 - .53). This questionnaire can be used in research on the development of
      psychological complaints of caregivers, but also for measuring the effect of an
      intervention on caregivers.

PMID- 8750984
TI  - [Will modernization of elderly care finally start].

PMID- 8750983
TI  - [Informal care; a critical observation].
AB  - In this article the policy aimed at cutting down expenses for professional care
      and at optimizing the contribution of informal, unpaid care (e.g. family
      caregivers and volunteers) is questioned. After a brief outline of the non
      professional care system for the elderly, some problematic aspects of informal
      care are discussed, especially the influence of such care in terms of
      (over)burden, the quality of care and the consequences for the relationship
      between caregiver and person being cared for. Voluntary services are also
      questioned, particularly the lack of control, the power of volunteers and their
      knowledge, attitude and skills. It is concluded that expectations towards
      nonprofessional caregivers should not be too great. The importance of a finely
      tuned coordination and clear division of tasks in the care network is underlined.
      Finally a number of recommendations is made to settle the observed bottlenecks.

PMID- 8750985
TI  - [Age-dependent idiopathic macular foramen. Current concepts of the pathogenesis,
      diagnosis, and treatment].
AB  - Senile macular hole usually affects only one eye. It is caused by tangential
      contraction of the premacular vitreous cortex, particularly that in the foveolar
      area. Its early stages produce characteristic biomicroscopic findings. In
      approximately 50% of cases, spontaneous vitreofoveal separation and recovery of
      vision occurs. Differentiation between a stage 1 impending hole and a stage 2
      hole may be difficult. A stage 2 hole may begin as either a central foveolar
      dehiscence or as a foveolar tear. In both cases, the holes may be accompanied by
      a similar appearing prehole opacity (pseudo-operculum in the former, and an
      operculum in the latter cases) in 75 to 80% of the cases. The visual prognosis is
      probably better in patients whose hole begin in the center. Histopathological
      examination of the prehole opacity for evidence of retinal tissue at the time of
      surgery should provide us with important information concerning the relative
      frequency of the two types of hole development. Meanwhile, there is accumulating
      circumstantial evidence to suggest that the majority of macular holes begin as a
      central dehiscence with little loss of retinal tissue and enlarge as a result of
      centrifugal displacement and concentration of the retinal receptors around the
      hole, and that visual improvement following surgery occurs not only because of
      reattachment of the retina, but also centripetal movement of the retinal
      receptors. Results of a small randomized study of treatment of stage 1 impending
      holes, while inconclusive, suggest that surgery is of little benefit. Although
      uncontrolled pilot studies of surgical treatment of full-thickness holes are
      encouraging, we must await results of the randomized trials to know its value.

PMID- 8750986
TI  - [Binocular vision in idiopathic macular foramen. Pre- and postoperative
      findings].
AB  - In recent years idiopathic macular hole has become an increasingly frequent
      indication for vitrectomy. To our knowledge, the literature contains no studies
      comparing binocular vision before and after vitrectomy. We therefore carried out
      a prospective study not only on visual acuity following vitrectomy but also, for
      the first time, on binocular vision. Stereopsis and fusion were evaluated in 37
      patients with idiopathic macular holes (stage I-IV) using Bagolini striated
      glasses, the Titmus stereotest (contour stereopsis), the random dot test (global
      stereopsis), the Worth four-dot test and the phase-difference haploscope. The
      tests were performed preoperatively and 10-12 weeks after vitrectomy. Two
      patients with stage I macular hole showed no loss of stereopsis in conventional
      tests. One patient, however, exhibited suppression tendencies with partial
      exclusion. The 18 patients with stage II macular hole had a relative good visual
      acuity of 0.2-0.6, but subnormal binocular vision with marked suppression of
      foveal images. Postoperatively, the majority of these patients had symptom-free
      binocular vision and good stereopsis. Some, however, continued to experience
      foveal exclusion. Patients with macular hole stage III and IV (n = 17) had the
      poorest results. Although the postoperative visual acuity improved by 2 to 3
      points in some patients (n = 6), in approximately one third it remained limited
      to global peripheral binocular vision. In summary, our findings show that even in
      early stages (I and II), macular hole can cause not only reduced visual acuity
      but also impairment or, in stage II, even loss of binocular vision. Vitrectomy in
      these early stages often leads to an overall improvement in visual acuity and
      binocular vision, whereas in more advanced stages vitrectomy often does not
      affect visual acuity and binocular vision. This should be taken into account when
      weighing up the indications for surgery.

PMID- 8750987
TI  - [Surgical extraction of subretinal pseudotumors in age related macular
      degeneration. Clinical, morphologic and immunohistochemical results].
AB  - We extracted massive disciform subretinal lesions in eight eyes of seven patients
      with age-related macular degeneration via pars plana access. The lesions were 4
      12 mm. All eyes had additional pathological findings such as PVR detachments,
      vitreous hemorrhage or acute submacular hemorrhage, sometimes in combination with
      each other. In seven eyes the preoperative visual function was no better than
      perception of hand movements, in 1 eye 1/35. The postoperative visual acuity was
      in 1 eye 0.3, in 6 eyes between 1/50 and 1/10 and without improvement in 1 eye.
      An intraocular silicone oil tamponade (highly purified, 5000 cs) was used in all
      cases. In two eyes the postoperative complication was central submacular
      fibrosis, and in two eyes with large retinotomies over more than two quadrants
      there were PVR reactions that needed reoperation in one eye. One patient was
      operated on bilaterally with final visual acuities of 1/35 and 1/10. The
      morphological structure of the extracted disciform lesions was characterized by a
      central fibrotic zone surrounded by attached hematomas, which were organized from
      the central tissue. In the central parts histology showed single layers of
      pigmented cells arranged along a basal membranelike PAS-positive band. Cell
      differentiation revealed macrophages, fibroblasts, myofibroblasts, T-lymphocytes,
      and vascular cells with immunohistochemical positive stainings for CD 68,
      cytokeratin, vimentin, alpha-actin, UCHL-1, and factor VIII. The lesions were
      supplied by a main choroidal vessel with branches into the periphery of the
      tissue. This feeder vessel can cause severe intraocular hemorrhage when it
      ruptures during surgical tissue extraction. Further immunohistochemistry showed
      the presence of cell adhesion molecules such as fibronectin, VLA-2, VLA-5, and
      VLA-6, the vitronectin receptor, 1CAM-1, LFA-1, and the PDGF receptor B. Their
      presence reflects mechanisms of growth regulation. The surgical extraction of
      massive submacular disciform lesions is part of the treatment of selected cases
      of end stages in age-related macular degeneration.

PMID- 8750988
TI  - [Results of perifoveal argon laser coagulation of subfoveal choroid
      neovascularization in age related macular degeneration].
AB  - BACKGROUND: The treatment of patients with subfoveal choroidal neovascular
      membrane in age-related macular degeneration is unsatisfactory because only a
      limited number of patients are eligible. The aim of this study was to
      prospectively evaluate a new perifoveal treatment technique in patients with
      subfoveal choroidal neovascular membrane. METHODS: Between April 1992 and January
      1994, 385 patients underwent clinical examination and fluorescein angiography.
      Eligibility criteria were met by 21 (5.5%) patients (22 eyes): well or poorly
      defined subfoveal choroidal neovascular membrane (< or = 3.5 disc diameters),
      without fibrosis, with visual acuity < or = 0.25. Visual acuity, morphological
      findings and complications were studied. The follow-up period was 12-32 months.
      RESULTS: The visual acuity before laser treatment ranged from counting fingers up
      to 0.25 (median 0.06). At the end of the follow-up (median 18 months) 28% (6/21)
      of patients showed a better visual acuity, whereas 44% (9/21) were unchanged and
      28% (6/21) had deteriorated compared to visual acuity before treatment. In 71%
      (15/21) of eyes, resolution of the choroidal neovascular membrane was achieved
      with development of an atrophic laser scar. CONCLUSION: The visual outcome and
      the morphological findings after perifoveal laser treatment of subfoveal
      choroidal neovascular membrane in age-related macular degeneration show it to be
      an alternative method of treatment with favourable results. Due to inclusion
      criteria it is suitable only for a limited number of patients.

PMID- 8750990
TI  - [Central serous chorioretinitis. Therapy experience over 20 years with and
      without laser coagulation].
AB  - Since 1969, 1,179 eyes with central serous chorioretinopathy have been examined
      with fluorescein fundus angiography. The classic form with fluorescein leakage
      (type I) decreased in incidence from 86.4% to 55.4%, while an atypical form with
      frequent serous pigment epithelial detachment (type II) increased from 12.6% to
      33.0%, and the mixed form (type I + II) increased from 1 to 11.6%. In type I with
      delayed healing laser coagulation of the leakage was performed, which improved
      the visual acuity from 0.64 to 0.92 an average (n = 122), while in cases without
      laser coagulation the percentage improved only from 0.66 to 0.84 on average (n =
      34) with a statistically significant difference (t = 2.64, P < 0.01). Laser
      coagulation was especially beneficial in the mixed form (n = 16), in which the
      visual acuity improved from 0.42 to 0.86 on average. The proportion of women
      increased from 10.7 to 17.9%. The patient age tended to be higher in women more
      than in men.

PMID- 8750989
TI  - [In vivo fundus fluorescence measurements in patients with age related macular
      degeneration].
AB  - This study was performed to measure and characterize the intrinsic fluorescence
      of the ocular fundus in patients with age-related macular degeneration (AMD).
      METHOD: Fluorescence spectral measurements from discrete retinal locations were
      made using the fundus spectrophotometer with excitations at 470 and 510 nm. Two
      normal subjects and seven patients with different stages of AMD were
      investigated. RESULTS: The spectral characteristics of fundus fluorescence are
      consistent with those of lipofuscin in the retinal pigment epithelium (RPE). The
      fluorescence spectrum is broad, with a maximum at about 620 nm. The shape and
      intensity of the fluorescence spectra are affected by age, site of measurement,
      pathology, ocular media absorption, and excitation wavelength. Spectra from areas
      with drusen reveal an additional fluorophore, with maximum around 560 nm,
      probably emanating from drusen and Bruch's membrane. Measurements in atrophic
      reveal a decrease of lipofuscin fluorescence and/or a contribution likely due to
      choroidal and sclera collagen fluorescence. Fluorescence from lipofuscin is more
      efficiently excited at 510 nm, whereas that of drusen and subretinal structures
      is relatively more efficient with 470 nm excitation, allowing for discrimination
      of various fluorophores. CONCLUSION: The spectral characteristics of RPE
      lipofuscin could be identified and quantified in AMD patients. In addition, the
      spectra are affected by other fluorophores such as drusen and choroid
      contributions in atrophy. Fluorescence spectra measurements in AMD patients allow
      for discrimination of lipofuscin fluorescence, drusen fluorescence, and choroidal
      or scleral fluorescence. The non-invasive measurement of lipofuscin and drusen
      fluorescence in AMD may be helpful in monitoring the disease, understanding its
      evolution, and testing therapeutic concepts.

PMID- 8750991
TI  - [Endotamponade with silicon oil in severe proliferative retinopathy with attached
      retina].
AB  - Silicone oil as endotamponade in cases with attached retina is only indicated in
      a few very selected cases. These are cases with a high risk of intravitreal
      hemorrhage and a need for quick visual rehabilitation. We examined 23 patients,
      who had undergone pars plana vitrectomy and silicone oil filling. All patients
      were diabetics with proliferative retinopathy and recurrent intravitreal
      hemorrhage. In 14 cases it was the only eye; 11 eyes previously had a vitrectomy.
      We analyzed these cases for visual acuity, rubeosis, bleeding tendency,
      reproliferations, cataract development and glaucoma. The follow-up time was 32
      months. In 22 of 23 eyes quick visual rehabilitation was achieved, and the
      patients had at least ambulatory vision within the first week. In one case poor
      visual acuity was due to exudative maculopathy. No relevant bleeding occurred. In
      14 of 16 phacic patients we observed a cataract. Seven patients developed
      glaucoma, which was due to neovascularization in 5 cases. It was successfully
      treated in all cases and no visual loss occurred. In 5 cases we observed a
      peripheral traction retinal detachment, in one case a traction retinal detachment
      at the posterior pole. In selected cases silicone oil can prevent recurrent
      intravitreal hemorrhage, allowing rapid visual recovery. Considering the
      complications, the silicone oil should be removed as soon as possible.

PMID- 8750992
TI  - [Toxic substances with silicone oil after intraocular injections].
AB  - In articles about the analysis of intraocular silicone oil, mostly the amount and
      toxicity of low-molecular-weight components (LMWC) have been investigated. This
      study was intended to analyze the components of silicone oil following a longer
      intraocular application. We analyzed silicone oil removed from human eyes with
      PVR a few months postoperatively. The fraction of LMWC was further investigated
      and we separated 16 different components belonging to hexachlorhexanes (HCH),
      polybiphenyls (PCB) and dichlor-diphenyl-trichlorethane (DDT). All these
      substances are said to have a toxic and cancerogenic effect as well as weakening
      the immune system. The concentration of these organic chloride components
      measured in intraocular injected silicone oil is about the same as fatty tissue
      but exceeds the concentration in human blood enormously. Possible damage to the
      retina by these toxic substances is another reason for early removal of silicone
      oil if the situation of the retina is stable.

PMID- 8750993
TI  - [Primary vitrectomy in rhegmatogenous retinal detachment].
AB  - For therapy of uncomplicated rhegmatogenous retinal detachment, a buckling
      procedure is the standard surgical technique today. In complicated cases, e.g.,
      retinal redetachment after a failed buckling procedure, vitrectomy is
      established. Meanwhile it is being discussed whether or not certain retinal
      detachments, e.g., with atypically large tears, should be treated with primary
      vitrectomy. We studied retrospectively all primary vitrectomies for retinal
      detachment without proliferative vitreoretinopathy (PVR) that were operated upon
      during 1992 in Wurzburg Eye Hospital (32 patients). In 56% (18 eyes) of the
      patients a subtotal or total retinal detachment was seen preoperatively; in 47%
      (15 eyes) the macular region was detached. In 25% (8 eyes) large retinal tears
      were seen (> 1 h). The other patients showed atypical horseshoe tears partly
      central to the equator or multiple holes. Seventy-eight percent (25 eyes) of all
      cases were successfully vitrectomized with one operation and revealed good
      results using intraocular tamponade (SF-6/air mixture). Seven patients needed
      further vitrectomy partly using silicone oil as an intraocular tamponade. In
      cases of rhegmatogenous retinal detachment with atypical tears or non-identified
      holes, vitrectomy without the buckling procedure is a good alternative, because
      the rate of successful results is as high as what is achieved with buckling
      procedure in uncomplicated cases.

PMID- 8750994
TI  - [Long-term outcome after silicone oil removal].
AB  - In order to reduce the incidence of postoperative complications in silicone
      filled eyes, many authors recommend that silicone oil should be removed from the
      eye as soon as a stable retinal situation is achieved. Even in the eyes with
      completely attached retina and a clinically stable situation there is a risk of
      retinal redetachment and other complications after silicone oil removal. In a
      retrospective study we analyzed 324 cases after silicone oil removal regarding
      the postoperative redetachment rate and risk of complications from this
      procedure. The indication for primary surgery was retinal detachment with PVR in
      167 (51.5%) cases, proliferative diabetic retinopathy in 87 cases (26.8%),
      complications of penetrating ocular injuries in 48 cases (14.8%), giant tear
      retinal detachment in 9 cases (2.7%) and retinal detachment with a central hole
      in 13 cases (4%). At the time of silicone oil removal retina was completely
      attached in 277 eyes. Local retinal redetachment central to the encircling band
      existed in 47 eyes at the time of silicone removal. Follow-up time ranged from 6
      63 months. Silicone oil removal was combined with a cataract operation in 42
      cases (12.9%), penetrating keratoplasty in 9 cases (2.8%) and membrane peeling in
      54 eyes (16.7). In the postoperative period the retina detached in 39 (12%) eyes.
      In the eyes with preoperatively completely attached retinas, redetachment
      occurred in 23 eyes (8%), whereas in the group of eyes with an unstable
      preoperative retinal situation, the retina redetached in 16 eyes (34%). The
      duration of the silicone oil tamponade had no effect on the redetachment rate. In
      the group of eyes with an unstable preoperative retinal situation, preoperative
      laser photocoagulation at the cerelage buckle, as well as central to the local
      detachment, reduced the incidence of redetachment after silicone oil removal
      significantly (25% vs. 53%). In the group of eyes with a preoperatively stable
      retinal situation, this effect was not significant. Our results show that in eyes
      with completely attached retinas, the risk of complications and redetachment
      after silicone oil removal is relatively low. In selected cases, even in eyes
      with incompletely attached retinas, silicone oil could be removed. Nevertheless,
      a relatively high risk of postoperative complications has to be taken into
      consideration. In eyes with an incompletely attached retina, preoperative laser
      photocoagulation at the cerclage buckle, as well as central to the local
      redetachment significantly reduced the incidence of redetachment after silicone
      oil removal.

PMID- 8750995
TI  - [Changes in bulbus geometry after conventional detachment surgery. Study using
      video keratoscopy].
AB  - Conventional detachment surgery produces scleral indentation and can therefore
      lead to changes in the geometry of the bulbus. The aim of this research was to
      analyze the influence of scleral buckling (group A) and encircling elements
      (group B) on corneal topography, surgical induced astigmatism and axial length.
      In 19 cases with peripherally detached retinas we performed keratometry,
      videokeratoscopy and measured axial length preoperatively in the first week as
      well as 1 and 3 months postoperatively. Total preoperative astigmatism in group A
      was 0.49 D and in Group B 0.84 D. The surgically induced astigmatism calculated
      by vectoral analysis was in the first postoperative week 0.98 D and 1.92 D. 1
      month postoperatively it was 0.74 D and 1.26 D, and after 3 months 0.89 D and
      1.31 D. There was minimal change in the average axial length: 0.09 mm reduction
      in group A and 0.21 mm increase in group B after 3 months. Computerized
      videokeratoscopy was very effective in determining this slight, surgically
      induced astigmatism.

PMID- 8750996
TI  - [Evaluation of published recommendations for screening studies of retinopathy of
      prematurity].
AB  - PURPOSE: Evaluation of different and partially contradictory guidelines for
      screening for retinopathy of prematurity published in Germany. PATIENTS: The data
      on 1219 preterm infants examined in Bern (n = 900) and Berlin (n = 319) were
      analyzed. A total of 680 preterm infants (56%) had a birth weight below 1500 g.
      The remaining infants were examined because oxygen had to be supplied or surgery
      done before or around the estimated delivery time. RESULTS: Stage 3 retinopathy
      was found in 88/1219 (7.2%) preterm infants. Only 5/88 infants weighed more than
      1500 g at birth. Three of these infants had a birth weight below 2000 g and
      needed supplemental oxygen for a prolonged period of time. The other 2 infants
      had birth weights of more than 2000 g and were severely ill. Of 1219 preterm
      infants, 37 (3%) developed threshold retinopathy (according to the criteria of
      the multicenter trial); 35/37 infants weighed less than 1230 g at birth. The
      remaining 2 children (1650 g and 2185 g birth weight) were severely ill.
      CONCLUSIONS: Preterm infants should be screened for retinopathy of prematurity:
      (1) if the birth weight is below 1500 g; (2) if the birth weight is below 2000 g
      and oxygen supply was necessary for more than 30 days; (3) if infants are very
      sick or must undergo multiple surgery before term. The first examination should
      be scheduled for the 6th week postnatal and not before 31 weeks postmenstrual
      age.

PMID- 8750997
TI  - [Vitreous involvement in cytomegalovirus retinitis].
AB  - In our outpatient department we often see patients with vitreous inflammation.
      Recent reports emphasize that vitreous inflammation is very rare, so we looked
      for patients with cytomegalovirus (CMV) retinitis and vitreous inflammation. We
      investigated 359 HIV-positive patients for at least 1 year; all patients reached
      the stage of AIDS disease. We included patients without any retinal signs of CMV
      retinitis at the beginning or CMV recurrence during the study. A slit-lamp
      investigation, binocular funduscopy and b-picture ultrasound were done at regular
      intervals. The results show an increase in vitreous inflammation with the
      frequency of CMV retinitis recurrences. Patients very often develop retinal
      detachment. Vitreous inflammation is a critical factor when examining CMV
      retinitis. In the future a larger series of patients should be examined.

PMID- 8750998
TI  - [Traction vitreoretinal opticopathy in proliferative diabetic vitreoretinopathy].
AB  - In patients with proliferative diabetic vitreoretinopathy the authors noticed
      tractive vitreoretinal distortion of the optic disk to the nasal side. As a
      result of this distortion a reduction in visual acuity, pallor of the optic disk,
      and changes in the visual evoked potentials were registered. The disease in
      called "tractive vitreoretinal opticopathy." METHOD: We examined 15 diabetics
      with vitreoretinal traction and temporal pallor of the optic disk, as well as a
      reduction in visual acuity. Six patients were observed retrospectively and 9
      patients prospectively before and after vitrectomy. Pre- and postoperative
      examinations included visual acuity, visual field, fluorescence angiography, and
      the conduction of visual evoked potentials (VEP). RESULTS: Within a postoperative
      follow-up of 2-8 months (mean 6.5 months) a return of optical vitality combined
      with an increase in visual acuity could be seen in 14 of 15 patients. In
      addition, some of the patients showed an improvement in the amplitudes and a
      reduction in the latency of the VEP. CONCLUSIONS: The authors assume that the
      axoplasmatic flow in the optic nerve fibers is reduced according to vitreoretinal
      traction. Furthermore, the traction may cause elongation of the capillaries,
      resulting in reduced perfusion of the optic disk. For these reasons early
      vitrectomy in patients with tractive vitreoretinal opticopathy is recommended.

PMID- 8750999
TI  - [PDGF-induced effect on cytosolic free calcium concentration of cultured retinal
      pericytes].
AB  - Although the selective loss of retinal pericytes has long been known to be one of
      the earliest histopathological findings in diabetic retinopathy, only limited
      information is available concerning their function and cell biology. Recently, it
      has been shown that the interaction of endothelial cells and pericytes plays an
      important role in the maintenance of vascular integrity. Additionally, it has
      been suggested that pericytes have a contractile function. Platelet-derived
      growth factor (PDGF), released from endothelial cells, has been shown to be a
      potent mitogen and vasoconstrictor. Cytosolic free calcium ([Ca2+]i) has been
      shown to play a key role as a second messenger for PDGF, involved in the
      regulation of various cellular functions, e.g. cell proliferation and vascular
      contractility. In order to characterize the effect of different PDGF homodimers
      on cultured bovine retinal pericytes, we investigated PDGF-AA- and -BB-dependent
      alterations in [Ca2+]i was determined with the Ca(2+)-sensitive fluorescent probe
      Quin-2. Basal levels were 118 +/- 30 nM. Stimulation with PDGF-BB in
      concentrations ranging from 5 to 20 ng/ml led to a dose-dependent increase of
      [Ca2+]i with an EC50 of 5.8 ng/ml. Maximum stimulation, to about 280% of basal
      levels, occurred after 3-4 min. In contrast, PDGF-AA was not effective. The
      results suggest that PDGF-BB may influence the integrity and contractility of the
      retinal microvasculature via modulation of the intracellular calcium homeostasis
      of pericytes. Additionally, it can be speculated that cultured retinal pericytes
      express mainly PDGF-beta-type receptors.

PMID- 8751000
TI  - [Idiopathic juxtafoveolar telangiectasis. Long-term follow-up of visual acuity].
AB  - The beneficial effect of laser therapy on idiopathic juxtafoveolar telangiectasis
      is questionable. We therefore studied retrospectively the spontaneous course of
      the disease and tried to show a correlation between the initial angiographic
      findings and visual outcome. In addition, the results after laser therapy were
      compared with untreated patients. Thirteen patients (24 eyes) with idiopathic
      juxtafoveolar telangiectasis diagnosed by fluorescein angiography were reexamined
      after a mean time interval of 38 months. Argon laser coagulation had been
      performed in 6 patients. The initial extension of fluorescein leakage was divided
      angiographically into three different stages. The existence of secondary macular
      changes and peripheral involvement was noted. The mean visual acuity decreased
      from 0.71 to 0.62 over the follow-up period. No correlation could be found
      between the final visual outcome and initial extension of telangiectasis or
      existence of secondary changes. After laser coagulation the patients did not show
      a better visual outcome. Due to the relatively benign spontaneous course of
      idiopathic juxtafoveolar telangiectasis laser coagulation cannot be recommended
      in general. Only in exceptional cases (e.g., development of subretinal
      neovascularization) can laser coagulation be of benefit.

PMID- 8751001
TI  - [Social ophthalmologic aspects of retinitis pigmentosa].
AB  - Inherited retinal degenerations cause severe visual handicaps or blindness later
      in life. In typical rod cone dystrophy (retinitis pigmentosa) there is relevant
      visual loss in the third decade with implications for the patients' professional
      life, their mobility and their private life. For this reason, the disease is
      relevant for the individual patient as well as for society in general. We
      investigated social issues in 233 retinitis pigmentosa patients: 9.9% are not
      able to read any more; 40.9% have never had a driver's license and 27.8% quit
      driving because of a visual handicap. The mean reduction in the capacity for work
      is 86%; 12.7% are unable to work and therefore receive public financial support;
      22.6% are unable to work in their profession; 20.9% are receiving public support
      because of legal blindness. Against this background it seems to be important that
      ophthalmologists inform their patients thoroughly about the implications of the
      disease for their professional and private lives. Doing this, he/she should ask
      for support from social service professionals.

PMID- 8751002
TI  - [Incidence of ophthalmologic complications in acute intracranial hypertension].
AB  - Although Terson's syndrome has been diagnosed more frequently since the early
      1960s because of improved intensive-care facilities, these reports are single
      case reports or retrospective studies. Therefore, we examined prospectively 20
      patients (11 male, 9 female), aged between 23 and 77 years, with subarachnoid
      hemorrhages or rapid increase in intracranial pressure (ICP) of other origin
      (tumor-associated, post-traumatic) to evaluate ocular changes. In all patients
      the increase in ICP was confirmed by computed tomography. Additionally, in 16
      patients permanent monitoring of ICP was performed. Twelve patients presented
      with subarachnoid hemorrhage, 6 had a post-traumatic increase in ICP, and 2 more
      presented with a tumor-associated intracranial hemorrhage. A total of 8 patients
      (40%) presented with intraocular changes; 6 presented with uni- or bilateral
      intraretinal hemorrhage, 1 patient had a bilateral papilledema and 1 more patient
      had bilateral vitreal hemorrhage. When ocular hemorrhage occurred, the mortality
      was 2.5 times as high as in patients without ocular hemorrhage. For this
      prognostic feature of the ophthalmological status all patients with rapid
      increase in ICP should be monitored early for intraocular hemorrhage. The
      possibility of intraocular hemorrhage is elevated in high-degree subarachnoid
      hemorrhage, whereas a rapid increase in ICP also found when the pressure has
      other causes (tumor-associated, posttraumatic).

PMID- 8751003
TI  - [Prognostic factors in selected stab injuries of the posterior eye segment].
AB  - Vitreoretinal proliferation (PVR) is an important cause of severe visual loss in
      eyes with penetrating injuries. The aim of this work was to study the occurrence
      of early signs of PVR in eyes with penetrating injuries and no indication for
      vitrectomy within the first 14 days and to identify the factor that correlates
      most with high incidence and early onset of PVR. Furthermore, the aggressiveness
      of PVR in this group of patients was studied. We examined 51 patients (mean age
      36 years) with penetrating ocular injuries using indirect ophthalmoscopy and B-
      and A/B-scan-echography. The mean follow-up interval was 24 months. The factor
      that correlated most with high incidence and early onset of PVR was a scleral
      laceration length of > 6 mm. The incidence of PVR was at any time significantly
      higher in eyes with a scleral laceration length of > 6 mm than in eyes with a
      scleral laceration length of < 6 mm (P < 0.0313). A negative correlation was
      shown between the length of the scleral laceration and the time of onset of PVR
      (r = 0.3441; P = 0.0006). Four eyes (8%) underwent vitrectomy because of
      aggressive development of PVR. A scleral laceration length of > 6 mm is the most
      important risk factor for high incidence and early onset of PVR in eyes with
      penetrating injuries with no indication for vitrectomy within the first 14 days.

PMID- 8751004
TI  - [Reflection measurement during retinal laser coagulation in patients. Development
      of an automatically controlled dosimeter].
AB  - PURPOSE: Retinal laser coagulation has limited reproducibility, because every
      laser exposition is unpredictably affected by pigmentation and media opacities.
      This can lead to complications. A feedback-controlled dosimeter would make
      retinal laser treatment a safer, more reproducible and faster procedure. METHOD:
      A reflectometer was developed that allows monitoring of the reflection of laser
      light during standard photocoagulation. Hundreds of coagulations in rabbit eyes
      and about 12,000 coagulations in patients undergoing routine laser treatment were
      recorded. RESULTS: The results of the first reflectance measurements in humans
      are presented along with extensive animal studies. A typical reflectance history
      was found for different lesion intensities. The degree of retinal whitening
      correlates with reflectance characteristics. These characteristics allow an early
      prediction of lesion intensity. Motion during laser exposure affects each
      coagulation in a fashion similar to spot size and exposure time. CONCLUSION:
      Reflectometry is the currently most effective means of monitoring lesion
      development. An automatic dosimeter for retinal photocoagulation seems feasible.

PMID- 8751005
TI  - [Antigen pattern in choroid melanoma in correlation with immunoscintigraphy].
AB  - We have reported that the sensitivity of immunoscintigraphy in ocular melanoma is
      fairly low in comparison with (metastasizing) cutaneous melanoma. No significant
      correlation was found between the histological data for ocular melanoma and the
      immunoscintigraphic results. We therefore wanted to see whether we could
      demonstrate an antigen pattern that was different from that of cutaneous
      melanoma, which might explain our previous results. Our study comprised tumor
      tissue from 20 patients with ocular melanoma who had undergone previous
      immunoscintigraphic examination. Using immunohistochemical techniques, tumor
      immunoreactivity was investigated against 225.28S, the antibody used for
      immunoscintigraphy, on cryosections in 12 cases, and against anti-HMB-45, and
      anti-S-100 and anti-vimentin on paraffin sections in all 20 patients. In summary,
      there was marked immunohistochemical heterogeneity, and none of the antibodies
      examined showed a significant correlation with immunoscintigraphy. Even 225.28S
      that was used for the immunoscintigraphic examination did not retrospectively
      allow a predictable immunoscintigraphic outcome. When comparing our results with
      the literature on cutaneous melanoma we were also able to confirm differences in
      immunoreactivity with regard to the other antibodies. We conclude that the
      comparatively poor results in ocular immunoscintigraphy obtained with 225.28S are
      due to antigenic differences between ocular and cutaneous melanoma.

PMID- 8751006
TI  - [Adaptive procedures for measuring arterial blood flow velocity in retinal
      vessels using indicator technique].
AB  - There are highly significant differences in the measuring results of arterial
      blood velocity between the indicator and laser-Doppler techniques (up to 800%). A
      new measuring procedure for the analysis of indicator dilution curves was
      developed based on indicator model and experimental results. The use of this new
      measuring procedure results in reduced mean systematic error between the
      indicator and laser-Doppler techniques to values around 10%. With the
      introduction of adaptive measuring arrays for the creation of indicator dilution
      curves and the application of adaptive algorithms for centering and spectral
      normalizing of the dilution curves, improved reproducibility can be expected.

PMID- 8751007
TI  - [Case study of a solitary vitreous body cyst].
AB  - Vitreous cysts are rare and their origin unclear. We present a case of a 47-year
      old woman who, after undergoing retinal detachment surgery on several occasions,
      developed disturbing vitreous opacities with which she presented for possible
      vitrectomy. Besides the typical postoperative vitreous condensations and
      opacifications, a solitary spherical cystic structure was present in the anterior
      vitreous cavity. The cystic structure was attached at its posterior aspect onto a
      vitreous membrane and was otherwise floating within a vitreous body lacuna. The
      vitreous opacities and the cyst were removed by performing a pars plana
      vitrectomy. The patient's visual acuity improved from 0.5 to 0.7. We presume that
      the cyst was acquired in association with the retinal detachment or the
      operations.

PMID- 8751008
TI  - [Subretinal manifestations as the chief findings in parasitic diseases in
      germany].
AB  - The most frequent intraocular manifestations of parasitoses in Germany and world
      wide are retinochoroidal lesions of Toxoplasma gondii; worms are less frequent.
      In reports of four cases it is shown that demographic data, biomicroscopical
      hallmarks and the fecal wet-mounts are the most important parameters for a
      presumptive diagnosis, if no intraocular material can be isolated. The patients
      in this series lack systemic features and changes in the blood differential,
      probably due to the adequate alimentary state and lack of reinfestations.

PMID- 8751009
TI  - [Morphologic changes in the lens epithelium in patients with age-induced
      cataract, radiation and steroid cataract and cataract following eye contusion].
AB  - The lens epithelium of the human eye plays a crucial role in the pathogenesis of
      primary and secondary cataract. Sixty hematoxylin-eosinstained lens epithelia
      were examined using a light microscope. Cell parameters were compared to one
      another in the various age groups of patients, between patients with secondary
      cataract (radiation cataract, steroid cataract and traumatic cataract) and
      patients with senile cataract, and between male and female patients. The t-test
      was used for statistical comparison. The median cell density was 3116.5
      cells/mm2. The median nucleus-plasma ratio was 1:2.74. Patients with secondary
      cataract had a larger medium cell and nucleus area as well as a higher nucleus
      plasma ratio and a lower cell density than patients with senile cataract. A part
      from degenerative and proliferative cell changes we found various cell types. The
      age of patients and the cause of cataract correlate with morphometric changes of
      lens epithelium cells. However, there was no correlation between specific
      cytologic changes and causes of cataract.

PMID- 8751010
TI  - [Morphometry of the ciliary body using ultrasound biomicroscopy].
AB  - High-frequency ultrasound biomicroscopy (UBM) is a new method which allows in
      vivo visualisation of anterior segment structures with high resolution but
      limited penetration. Using this modality we wanted to examine the ciliary body
      and measure its total length and depth and look for correlations with the axial
      eye length. A special technique with external markers was developed to measure
      the total length of the ciliary body using two UBM pictures. In 83 patients the
      mean ciliary body length was 5.2 mm nasally and 5.7 mm temporally. The depth of
      the ciliary body was 1.2 mm nasally and 1.4 mm temporally. A correlation could be
      demonstrated between the axial eye length and the ciliary body measurements. As
      our measurements are reproducible and consistent with recent histological
      studies, high-resolution UBM can be regarded as a reliable method for in vivo
      visualisation and quantitative analysis of the ciliary body.

PMID- 8751011
TI  - [Centering the posterior chamber lens in autopsy eyes with and without
      pseudoexfoliation syndrome].
AB  - The pseudoexfoliation syndrome (PEX) is an important risk factor for cataract
      surgery. In this study we examined a series of 24 autopsy eyes with PEX that had
      undergone cataract surgery and intraocular lens (IOL) implantation. The eyes were
      grossed for IOL fixation and centration. The results were compared to a control
      group of 25 non-PEX autopsy eyes that matched the PEX series in age distribution,
      implant duration and anatomical parameters (i.e., axial length) (P > 0.18). The
      mean IOL decentration in all PEX eyes (0.75 +/- 0.38 mm) was significantly higher
      than in the control group (0.40 +/- 0.29 mm) (P = 0.0008). Analysis of subgroups
      with symmetrical bag/bag fixated IOLs also showed significant higher decentration
      in the PEX group (P = 0.04). The main reason for decentration was decentration of
      the entire capsular bag in the PEX eyes (0.28 +/- 0.19 vs 0.10 +/- 0.16 in
      controls; P = 0.001). Patients with PEX showed a higher amount of IOL
      decentration. The results indicate that the insufficient suspension apparatus of
      the lens and decentration of the entire capsular bag are the main reasons for IOL
      decentration in patients with PEX.

PMID- 8751012
TI  - [Neuroradiology in ophthalmology. 2].

PMID- 8751013
TI  - Thalidomide-induced neuropathy and genetic differences in drug metabolism.
AB  - A pharmacogenetic predisposition to thalidomide-induced neuropathy has been
      investigated. Differences of drug metabolism were examined in 16 patients with
      severe orogenital ulceration, who were treated with thalidomide (< or = 200
      mg/day) for 0.3-5.0 years. Eight had evidence of early peripheral neuropathy
      according to nerve conduction studies. Rates of C-hydroxylation, N-acetylation,
      and conjugation reactions with sulphate, glucuronide and glycine, were tested
      with the probe compounds debrisoquine, sulphadimidine, paracetamol and aspirin,
      respectively. Urinary drug metabolites were analysed by high pressure liquid
      chromatography. Results were compared with 16 healthy age- and sex-matched
      volunteers. Of the patients 6.25% and 13.3% of the controls had a poor
      Debrisoquine Hydroxylator Ratio (DMR); none of the patients with neuropathy had a
      poor DMR as compared to 12.5% without neuropathy. Of the patients 40.0% and 35.7%
      of the controls were slow acetylators; 28.6% with neuropathy were slow
      acetylators as opposed to 50% without neuropathy. Similarly, there were no
      significant differences in rates of conjugation between groups. All unaffected
      patients were active smokers, whereas only two of those with neuropathy smoked.
      Cumulative dose or duration of therapy were unrelated to risk of neuropathy. In
      conclusion, changes of nerve conductivity are a frequent and unpredictable
      adverse effect of thalidomide (< or = 200 mg/day), although smoking may have a
      protective action against their development. Nerve conduction studies are
      required before and during treatment, irrespective of the prescribed dose.

PMID- 8751014
TI  - Tonic versus phasic pain: dose-related effects of ketoprofen.
AB  - Only recently has a new experimental technique been developed which combines
      tonic and phasic painful stimulation. By means of this technique the non
      steroidal anti-inflammatory drug (NSAID) ibuprofen has been shown to produce a
      dose-related decrease in heterotopically applied phasic and tonic pain. The
      present study aimed to investigate the dose-related effects of the NSAID
      ketoprofen (50, 100, and 150 mg i.v.) when tonic and phasic stimuli were applied
      homotopically. Eighteen healthy volunteers participated in the double-blind,
      randomized, placebo-controlled study. After an initial training session subjects
      took part in four experiments, each of which was divided into three sessions
      (before, 30, and 120 min after drug administration). During each session 45
      painful phasic CO2 stimuli of three concentrations were presented to the left
      nostril in randomized order (duration 200 ms; interval 40 s; 45%, 52%, and 59%
      v/v CO2). The left nostril was additionally stimulated with a constant stream of
      dry air, which produced a tonic painful sensation described as dull and burning.
      Subjects rated the intensity of the painful stimuli by means of visual analogue
      scales. Chemosomatosensory event-related potentials (CSSERPs) were recorded in
      response to phasic painful CO2 stimuli. Ketoprofen reduced the subjects'
      estimates of tonic pain in a dose-related manner. In contrast, given the special
      conditions of homotopic application of tonic and phasic painful stimuli,
      estimates of phasic pain increased significantly, corresponding to a significant
      increase in CSSERP amplitudes. An explanation of this inverse effect of the drug
      on responses to tonic and phasic pain may be a lateralized interaction between
      both C-fiber and A delta-fiber systems at a spinal or peripheral level.

PMID- 8751015
TI  - Effects of lisinopril on congestive heart failure in normotensive patients with
      diastolic dysfunction but intact systolic function.
AB  - This study examined the effects of lisinopril on diastolic function in 12
      normotensive patients (mean age 72 years) with symptomatic congestive heart
      failure, intact left ventricular systolic function and abnormal diastolic
      function secondary to ischaemic heart disease in a placebo-controlled double
      blind crossover study, with each treatment dosed orally for 5 continuous weeks.
      Compared to placebo, lisinopril significantly decreased blood pressure, increased
      plasma renin activity without altering heart rate or plasma norepinephrine. There
      was no statistically significant improvement with lisinopril in radionuclide
      derived peak filling rate and time to peak filling rate, in Doppler
      echocardiographic measurements of the ratio of peak flow velocity in early
      diastole to the peak flow velocity of atrial contraction (E:A ratio) and in
      visual analogue scales of symptoms. Thus, although angiotension converting enzyme
      inhibitors may have an established role in the treatment of heart failure
      secondary to left ventricular systolic dysfunction, its use in patients with
      isolated diastolic dysfunction remains unclear.

PMID- 8751016
TI  - Lisinopril is neutral to insulin sensitivity and serum lipoproteins in essential
      hypertensive patients.
AB  - To investigate the effects of antihypertensive treatment with the angiotensin
      converting enzyme (ACE) inhibitor lisinopril on insulin sensitivity and related
      metabolic variables, the insulin sensitivity index (SI), determined with the
      Minimal Model Method of Bergman, fasting plasma insulin and glucose
      concentrations, serum total triglyceride and lipoprotein cholesterol fractions,
      and blood pressure were assessed in 24 lean, non-diabetic patients with essential
      hypertension. Following a double-blind, randomised crossover design, these
      parameters were measured after a 4-week run-in period, after 8 weeks of
      lisinopril or placebo, and after an additional 8 weeks on placebo or lisinopril,
      respectively. Furthermore, the level of physical fitness was estimated using the
      Conconi bicycle ergometer test. SI was low in this study population (5.6 vs 13.3
      x 10(-4).min-1.mU-1.l-1 in normal lean control subjects). It did not differ
      between the placebo run-in phase, the lisinopril phase, and the placebo crossover
      phase (5.8, 5.5, and 5.4 x 10(-4).min-1.mU-1.l-1, respectively). Moreover, during
      the administration of lisinopril, no significant changes occurred in fasting
      plasma insulin and glucose, areas under the glucose and insulin curves, glucose
      disappearance rate, serum total triglycerides, and cholesterol or lipoprotein
      cholesterol fractions. Heart rate at rest, body weight, and anaerobic threshold
      remained stable throughout the study. Compliance assessed by pill-counting
      exceeded 90% at all visits. These findings demonstrate that the ACE inhibitor
      lisinopril is neutral with regard to insulin sensitivity, plasma insulin and
      glucose, and lipoprotein metabolism in patients with essential hypertension.

PMID- 8751018
TI  - Diuretic-related hypokalaemia: the role of diuretics, potassium supplements,
      glucocorticoids and beta 2-adrenoceptor agonists. Results from the comprehensive
      hospital drug monitoring programme, berne (CHDM).
AB  - All 5,047 consecutive inpatients admitted to the Internal Medicine Division of a
      teaching hospital (Zieglerspital, Berne) between 1982 and 1985 were registered in
      accordance with the CHDM (Comprehensive Hospital Drug Monitoring) questionnaire
      of adverse drug reactions (ADRs). Of them, 2,439 were treated with at least one
      potassium losing diuretic. The hospital records of the patients were reviewed
      with particular regard to serum potassium levels, and on the basis of this
      evaluation, the patients were assigned to four different diuretic treatment
      groups, and the incidence of hypokalaemia related to diuretic treatment was
      estimated. The overall rate of occurrence of hypokalaemia was 21.1% at a serum
      potassium level < 3.5 mmol.l-1, and 3.8% < 3.0 mmol.l-1. Hypokalaemia of less
      than 3.5 mml.l-1 developed 24.9% (217/870) of patients treated with potassium
      losing diuretics alone; in 19.7% (101/513) treated with potassium losing
      diuretics in conjunction with potassium substitution, in 15.1% (66/438) treated
      with a combination of diuretics (potassium losing with potassium sparing), and in
      20.0% (12/60) treated with combined diuretics and potassium substitution. Only
      the differences between the first and the two subsequent groups were
      statistically significant. The overall incidence of hypokalaemia below 3.0 +
      mmol.l-1 was significantly lower in the patients on combined diuretics without
      potassium substitution than in the patients on potassium losing diuretics with
      potassium substitution. Oral or parenteral administration of glucocorticoids
      (prednisone 5 to 2,000 mg/d) was a significant risk factor for hypokalaemic
      events. beta 2-Adrenoceptor agonists had not effect. The patient's age, sex,
      renal function and numbers of drugs received were evaluated in a multivariate
      analysis, in order to take into account their influence on the risk of developing
      hypokalaemia. The number of drugs above 12 (and, less importantly, female sex)
      was the main risk factor for this ADR. The comparison between hypokalaemia and
      hyperkalaemia in this group of inpatients showed the significance of reduced
      renal function in the occurrence of hyperkalaemia.

PMID- 8751017
TI  - Antianginal effect of conventional and controlled release diltiazem in stable
      angina pectoris.
AB  - Two preparations of diltiazem, controlled release (CR) given twice a day (b.i.d.)
      and plain given 4 times a day (q.i.d.), were compared in a multicentre, double
      blind, crossover study in 41 patients with stable angina pectoris. Therapeutic
      efficacy was assessed with maximal exercise tests, patient recordings on
      nitroglycerine consumption and angina attacks. No significant differences between
      the CR and plain tablets were seen in any of the efficacy variables. Maximal
      workload significantly increased from 127 W on placebo to 146 W on CR tablets and
      to 147 W on plain tablets. Anginal attacks/week significantly decreased from 11.7
      on placebo to 4.9 on CR tablets and to 5.0 on plain tablets. Consumption of
      nitroglycerine tablets/week significantly decreased from 6.3 on placebo to 2.6
      and to 3.4 on CR and plain-tablets, respectively. The number or the seriousness
      of the adverse events did not differ between the groups. The results imply that
      diltiazem CR b.i.d. is equally potent and safe as conventional diltiazem q.i.d.
      in the control of stable angina pectoris.

PMID- 8751019
TI  - Pharmacodynamic modelling of the drug-induced downregulation of a beta 2
      adrenoceptor mediated response and lack of restoration of receptor function after
      a single high dose of prednisone.
AB  - Changes in beta 2-adrenoceptor function by chronic dosing of beta 2-mimetics and
      the possible influence of a single dose of prednisone have been studied as
      changes over time in the concentration-effect relationship of the beta 2
      adrenoceptor agonist terbutaline. Hypokalaemia was used as the specific beta 2
      adrenoceptor mediated effect. 8 healthy volunteers were given subcutaneous
      terbutaline 0.01 mg.kg-1 BW on 3 occasions over a 10-day experimental protocol: 1
      Control experiment on Day 1; 2 After 7 days of oral terbutaline 5 mg t.i.d. (Day
      8); and 3 After 8 days on oral terbutaline and 12 h after prednisone 100 mg
      orally (Day 10). The time course of the terbutaline concentrations and
      hypokalaemia was related using a pharmacokinetic-pharmacodynamic model. A sigmoid
      and a threshold Emax model were used to relate drug concentrations to effects.
      The oral terbutaline treatment caused a 35% increase in the distribution volume
      of SC terbutaline. After one week on oral terbutaline the concentration-effect
      relationship was shifted to the right and was steeper, with a higher EC50 of
      terbutaline and higher values for the apparent threshold concentration. These
      observations are compatible with a decrease in receptor numbers after 7 days of
      terbutaline in a system characterised by the presence of spare receptors. The
      data after prednisone pretreatment showed an apparent decline in the baseline
      plasma potassium concentrations that could be included in the Emax model. There
      was no change in the concentration-effect relationship 12 hours after prednisone.

PMID- 8751020
TI  - Comparison of the effects of atropine in vivo and ex vivo (radioreceptor assay)
      after oral and intramuscular administration to man.
AB  - The effects of an oral dose of atropine (0.03 mg/kg body weight) and an IM (0.02
      mg/kg) dose on the heart rate and salivary flow in seven healthy adult volunteers
      were compared to see whether the oral dose was sufficient to inhibit vagal
      reflexes of the heart. Atropine concentrations in plasma were determined by an M2
      selective radioreceptor assay, and the in vitro occupancy of porcine cardiac M2
      cholinoceptors was measured in parallel. In ligand-binding studies, atropine has
      been shown to have a comparable affinity for human and porcine cardiac M2
      cholinoceptors (Ki 4.0 and 5.9, respectively). Slight changes in heart rate after
      oral administration were not significant. After IM administration, however, the
      heart rate increased significantly, by a maximum of 22 beats.min-1 after 45 min.
      The slight increase in heart rate after the oral dose corresponded to a receptor
      occupancy in vitro near the lower limit of detection, whereas the significant
      increase in heart rate after the IM dose corresponded to a receptor occupancy of
      up to 47%. The maximum reduction in salivary flow was similar after the oral and
      IM doses (84.3 and 87.5%, respectively). The almost complete inhibition of
      salivary flow could be explained by the lower vagal tone in the salivary glands
      compared with to the heart. The difference in the effect on heart rate was
      probably due to lower absorption of the oral dose. Thus, an oral dose greater
      than 0.03 mg atropine/kilogram body weight is required to compensate for low
      gastrointestinal absorption and to overcome the high vagal tone of the heart.

PMID- 8751021
TI  - Effect of 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) enantiomers, major
      metabolites of phenytoin, on the occurrence of chronic-gingival hyperplasia: in
      vivo and in vitro study.
AB  - The purpose of this study was to assess the possible role of the (R)- and (S)-
      enantiomers of the phenytoin metabolite p-HPPH in the pathogenesis of gingival
      hyperplasia (GH). About 98% of circulating p-HPPH is in the (S)-form. There were
      significant differences between patients with and without GH in (R)-p-HPPH level
      (0.055 vs 0.042 microgram.ml-1), both enantiomer/racemate level ratios, and R/S
      enantiomeric ratio (0.0313 vs 0.0232); an increase in serum (R)-p-HPPH level was
      observed in patients with GH. In separate experiments, the effect of p-HPPH
      enantiomers on the proliferation of the normal human dermal fibroblast was
      studied. The in vitro study showed that (R)-p-HPPH selectively stimulated
      fibroblast growth. The results suggest that the least abundant metabolite, (R)-p
      HPPH, is the most toxic with respect to gingival hyperplasia.

PMID- 8751022
TI  - A double-blind controlled evaluation of the sebosuppressive activity of topical
      erythromycin-zinc complex.
AB  - In a double-blind randomised study, 14 volunteers applied 4% erythromycin plus
      1.2% zinc (Zineryt lotion) and 4% erythromycin lotions, each on half of the
      forehead twice daily for 3 months. The sebum output was evaluated at 3-week
      intervals using the photometric and the lipid-sensitive film methods. Evaluations
      of casual level (CL) and sebum excretion rate (SER) were made with a Sebumeter,
      and total area of lipid spots (TAS) was measured on Sebutapes. Compared to
      baseline values, the formulation of the erythromycin-zinc complex induced
      significant reductions in SER after 6 and 9 weeks, and in CL and TAS at 3, 6, 9
      and 12 weeks. The mean reduction in TAS was over 20% for four successive 1-h
      samplings on completion of the study. Significant reductions in CL, SER and TAS
      were observed for the erythromycin-zinc formulation compared to the control
      lotion at 6 and 9 weeks, and also at 3 weeks for SER and TAS, and at 12 weeks for
      CL and TAS. This study indicates that sebum output is significantly reduced by
      the erythromycin-zinc complex. This reduction is theoretically beneficial for the
      acneic patient.

PMID- 8751023
TI  - Relationship between time of intake of grapefruit juice and its effect on
      pharmacokinetics and pharmacodynamics of felodipine in healthy subjects.
AB  - In this randomised, cross-over study, in nine healthy males given felodipine ER
      10 mg PO 200 ml grapefruit juice was found to increase the plasma levels of
      felodipine even when the juice was taken 24 hours before the drug. Grapefruit
      juice drunk simultaneously with and 1, 4, 10 or 24 hours before the drug
      administration resulted in a 32-99% increase in mean Cmax values of felodipine,
      relative to concomitant water and felodipine intake. The effect on AUC was also
      significant when juice was taken up to 10 h before the drug. The effect of the
      interaction decreased with increasing time between juice and drug intake. All
      treatments produced a significant decrease in diastolic blood pressure and an
      increase in heart rate in comparison with morning basal values. The change in
      haemodynamic variables was approximately the same after all treatment
      combinations. Headache was reported more frequently after treatments including
      grapefruit juice.

PMID- 8751024
TI  - Pharmacokinetics and pharmacodynamics of a single dose of recombinant human
      growth hormone after subcutaneous administration by jet-injection: comparison
      with conventional needle-injection.
AB  - The pharmacokinetics and pharmacodynamics of recombinant human growth hormone
      (rhGH) were studied after a single subcutaneous dose given by jet-injection, and
      have been compared with the results obtained after conventional needle-injection.
      Twelve healthy male volunteers completed an open label, randomised, two-way
      crossover study, with a 7-day washout period between the two single sc doses.
      Pharmacokinetic parameters were derived from rhGH concentrations in blood samples
      collected regularly over 24 h after dosing on Day 1 of each period. To
      investigate the pharmacodynamics, additional samples were taken for the analysis
      of somatomedin C (IGF-I) and free fatty acids (FFA). A higher and earlier Cmax
      was found after jet-injection (ratio (%) jet-injected/needle-injected 124; 90%
      confidence interval 108-142). The AUC0-infinity for rhGH were similar (ratio (%)
      jet-injected/needle-injected 98; 90%-confidence interval 93-103). Both treatments
      were associated with a significant and similar rise in IGF-I. Both
      administrations of rhGH were associated with identical rhythmical changes in FFA.
      The study indicates that jet-injected and needle-injected rhGH are bioequivalent
      with respect to the amount absorbed. The criterion for bioequivalence is not met
      for the rate of absorption. It is unlikely that the latter finding will influence
      the pharmacodynamics of rhGH, since bioequipotency was established for the effect
      on IGF-I generation. Jet-injection was safe in use and was generally well
      tolerated.

PMID- 8751025
TI  - European postmarketing surveillance of ramipril in hypertension. 1. Feasibility
      and study cohort.
AB  - A prospective observational cohort study of the angiotensin inhibitor, ramipril,
      was undertaken in four countries within the European Community-Netherlands,
      United Kingdom, Germany and Belgium. A total of 10,377 consecutive patients with
      essential hypertension were recruited to the study with the aim of follow-up for
      one year. Overall 37% of doctors who agreed to participate in the study actually
      enrolled at least one patient. One third of the doctors who enrolled patients in
      the study entered two thirds of patients studied. Some 15% of participating males
      and 27% of females were aged over 70 years. Newly diagnosed hypertensives
      comprised 22% of the study cohort, the proportion being highest in UK and
      Netherlands, whereas 53% were established hypertensives of two or more years'
      duration, the proportion being highest in Germany and Belgium. There were
      substantial differences among the participating countries in the concurrent
      treatment these patients were receiving for hypertension, with two or more co
      therapies being most frequent in Germany and Belgium. There were also substantial
      differences in co-therapies for concurrent diseases among the participating
      countries, reflecting both standard therapeutic practices in local areas and
      differences in marketing of drugs in the different countries. This report
      describes the initial findings of this multinational study and emphasises the
      need to consider several major potentially confounding variables in the analysis
      of the outcome events both in this study and in other collaborative observational
      international monitoring schemes for adverse drug reactions.

PMID- 8751026
TI  - Flucloxacillin associated cholestatic hepatitis. An Australian and Swedish
      epidemic?
AB  - The clinico-pathological entity of flucloxacillin-associated cholestatic
      hepatitis is described and the recognition and documentation of cholestasis
      associated with flucloxacillin and with related isoxazolyl-penicillins
      (cloxacillin, dicloxacillin) is examined on an international basis, with
      particular reference to Australia. Data were obtained from the literature, from
      the Australian adverse drug reaction monitoring agency and from the Collaborative
      Centre for International Drug Monitoring (World Health Organisation) in Sweden.
      Approximately 600 cases of flucloxacillin-associated cholestatic hepatitis were
      collected, as well as 164 cases associated with other isoxazolyl penicillins.
      Jaundice and pruritus may first appear several weeks after administration of the
      drug has ceased and typically are severe and protracted. Liver tests may be
      abnormal for months after symptomatic recovery. Death is uncommon. Liver
      pathology shows centrizonal bile stasis with portal tract inflammation and
      variable loss of bile ducts. Approximately 1 in 15,000 users of flucloxacillin
      will develop the reaction. Increasing age (> 55 years) and prolonged intake (> 14
      days) are particular risk factors. Cholestasis associated with
      cloxacillin/dicloxacillin appears to be similar in nature but is less well
      defined. Recognition and reporting of the reaction have been uncommon in the
      United Kingdom inter alia and high in Sweden and Australia, although estimates of
      risk have been similar. In Australia, the remarkably high rate of reports appears
      to be the result of sustained publicity for the reaction. There is only a trickle
      of reports of cholestatic hepatitis in association with the use of cloxacillin
      and dicloxacillin from the USA and Canada. The high level of awareness of the
      reaction and consequential regulatory action so far have not resulted in a
      diminution of its occurrence in Australia.

PMID- 8751027
TI  - References used in a drug information centre.
AB  - The literature sources used in 461 consecutive problem-oriented questions
      submitted during 1993 to a Drug Information Centre were reviewed retrospectively.
      Journals were the most frequently used literature source (36% of all quotations).
      Commonly used medical and clinical pharmacology journals, together with standard
      textbooks, provided the necessary information to solve more than 50% of drug
      information requests. Most questions could be answered by including the
      complementary use of the question/answer database Drugline. Drug information
      access is important for the improvement of rational use of drugs. According to
      the present study, this activity is possible with a fairly limited number of
      sources.

PMID- 8751028
TI  - Rising dose study of safety and tolerance of flunarizine.
AB  - In a recent NIH-sponsored parallel-group placebo-controlled blinded study of
      flunarizine for the treatment of partial-onset seizures, the flunarizine serum
      concentration was controlled to a constant level among patients in order to
      reduce response variability. Flunarizine was found to exhibit modest anti
      epileptic efficacy. A potential criticism of this study is that the chosen
      controlled concentration was too low to determine optimal efficacy. As a
      participating center in this study we investigated the effect of higher doses of
      open-label flunarizine on seizure frequency in 16 patients with refractory
      partial seizures. Following the completion of the blinded placebo/flunarizine
      phase, all patients were initiated at the flunarizine dose calculated to result
      in a serum concentration of 60 ng.ml-1. The dose was subsequently increased each
      8-12 weeks to a maximum of 2.7 times the initial dose. On the initial maintenance
      flunarizine dose, seizure control was improved, with an average seizure reduction
      of 47% compared to pre-blinded-phase baseline. When higher doses were
      administered, adverse reactions were more common yet improved seizure control did
      not occur in most patients. These findings complement those of the concentration
      controlled NIH study and suggest that appropriate flunarizine doses were utilized
      in that study.

PMID- 8751030
TI  - A placebo controlled clinical trial investigating the efficacy of a homeopathic
      after-bite gel in reducing mosquito bite induced erythema.
AB  - A randomised, placebo controlled clinical trial was conducted to examine the
      efficacy of a homeopathic after-bite gel in the symptomatic relief of mosquito
      bites. Sixty eight healthy volunteers were bitten under laboratory conditions by
      Aedes aegypti mosquitoes at three spots, on the ventral aspect of the forearm.
      One bite was treated with the homeopathic after-bite gel, another bite with a
      placebo gel which was identical in appearance and smell to the homeopathic after
      bite gel, and the third bite remained untreated. Immediately after the bites and
      1, 3, 6, 26 and 31 hours post-bite, the length and width of the erythema were
      measured with a calliper, and photographs were taken of the bite sites from which
      the size of the erythema was subsequently determined. This was followed by
      assessment of the extent of itching with a verbal analogue scale, and finally
      treatment took place. For each spot the total erythema was calculated as the area
      under the plotted curve of the erythema at different time points (mm2*h) and the
      total sum of the itch scores was determined. For the bites treated with the
      homeopathic after-bite gel the median total erythema was 10.500 mm2*h. For the
      spots treated with the placebo gel and the untreated spots the median total
      erythema was 12.900 mm2*h and 13.300 mm2*h, respectively. The difference between
      the spots treated with the homeopathic after-bite gel and the untreated spots
      came close to significance (two-tailed P = 0.06), which was not the case for the
      difference between the spots treated with the homeopathic after-bite gel and the
      spots treated with placebo gel (P = 0.13). After pooling the data of a very
      similar previous pilot study and the present study (ntotal = 83), the homeopathic
      after-bite gel was significantly superior to no treatment (two-tailed P = 0.003)
      as well as to placebo gel (two-tailed P = 0.03). Comparing itching after the
      three treatments, no significant differences could be demonstrated. The extent of
      itching was positively correlated with the area of the erythema (r = 0.63).
      Treatment of mosquito bites with the homeopathic after-bite gel will reduce the
      erythema compared to no treatment. Comparison with the placebo gel suggests it is
      the plant extracts which are the active components of this gel.

PMID- 8751029
TI  - Czech and Slovak spirapril intervention study (CASSIS). A randomized, placebo and
      active-controlled, double-blind multicentre trial in patients with congestive
      heart failure.
AB  - A randomized, double-blind, placebo- and active-controlled multicentre study with
      spirapril, a new angiotensin-converting enzyme inhibitor (ACEI), has been
      conducted in patients with chronic congestive heart failure (CHF) of NYHA classes
      II-IV. After a placebo run-in period of 1-4 weeks, patients were randomly
      assigned to one of five treatment groups: placebo (n = 48), spirapril 1.5 mg (n =
      48), spirapril 3 mg (n = 53), spirapril 6 mg (n = 51) or enalapril 5/10 mg (n =
      48). The primary objective was to assess changes in exercise tolerance, and the
      secondary objective was an assessment of cardiovascular signs and symptoms,
      quality of life, ejection fraction and chest X-ray findings. Exercise tolerance
      increased in all groups; however, no statistically significant differences were
      found between any of the groups. There was a statistically significant reduction
      of mortality in the pooled spirapril groups compared with placebo, and a trend
      for reduction of serious cardiovascular adverse events as well as duration of
      hospitalization. These effects and improvements in lung congestion appeared to be
      dose dependent. In patients with moderate to severe heart failure, the
      combination with first-generation calcium channel blockers had an unfavourable
      effect on exercise capacity and clinical parameters. Spirapril might be an
      effective alternative to enalapril in the treatment of patients with CHF. The
      role of the exercise tolerance test in establishing efficacy of ACEIs in CHF and
      the widespread use of nifedipine in CHF is questioned.

PMID- 8751031
TI  - Reduced platelet phenolsulphotransferase activity towards dopamine and 5
      hydroxytryptamine in migraine.
AB  - OBJECTIVE: The sulphation of the neurotransmitters dopamine and 5
      hydroxytryptamine, and of the prototypical xenobiotic 4-nitrophenol, by
      phenolsulphotransferases was measured in platelet homogenates prepared from a
      group of migraine sufferers and a group of control subjects. RESULTS: The
      activity of the M form of phenolsulphotransferase, responsible for the sulphation
      of dopamine and 5-hydroxytryptamine was significantly reduced in the migraine
      population, by 28% with dopamine as substrate and by 20% with 5
      hydroxytryptamine. The activity of the P form of the enzyme towards 4-nitrophenol
      was the same in both groups. We also report that the selective inhibition of P
      form phenolsulphotransferase by red wine is much more potent than previously
      thought, with a 2000-fold dilution of dealcoholised red wine having the ability
      to inhibit sulphation by this enzyme by 50%. CONCLUSION: Our findings suggest
      that a reduced capacity for sulphation and inactivation of biogenic amines and
      catecholamines may be related to susceptibility to migraine.

PMID- 8751032
TI  - Effects of cimetidine on pharmacokinetics and pharmacodynamics of losartan, an
      AT1-selective non-peptide angiotensin II receptor antagonist.
AB  - This was a 2-period randomized, crossover study in 8 healthy males to determine
      the effects of cimetidine (400 mg q.i.d. for 6 days) on the pharmacokinetics and
      pharmacodynamic effects of the angiotensin II receptor antagonist, losartan (100
      mg). Cimetidine increased the AUC for losartan 18% without affecting the AUC for
      E-3174, the active metabolite of losartan. The increase in plasma renin activity
      following losartan was not affected by cimetidine (maximum mean increases 12.6
      and 12.1 ng Ang I.ml-1.h-1 without and with cimetidine, respectively). These
      results indicate that cimetidine does not appear to alter the pharmacokinetics or
      pharmacodynamics of losartan to a clinically significant extent.

PMID- 8751033
TI  - Increase in plasma propranolol caused by nicardipine is dependent on the delivery
      rate of propranolol.
AB  - The influence of a single oral dose of nicardipine 30 mg on the pharmacokinetics
      and pharmacodynamics of propranolol 80 mg given as a conventional release
      formulation and as a slow release formulation was studied in two separate groups
      of 12 healthy volunteers. Nicardipine doubled the area under the curve (AUC) and
      Cmax of propranolol when given as a conventional formulation, but increased it
      only slightly when given as a slow release formulation. This pharmacokinetic
      interaction did not result in clinically relevant changes in pharmacodynamic
      responses. These results indicate that the enhancement of the bioavailability of
      propranolol by coadministration of nicardipine is dependent on the delivery rate
      of propranolol, suggesting that the interaction is mainly due to short-term
      haemodynamic effects of nicardipine leading to saturation of hepatic enzymes or
      functional shunting.

PMID- 8751035
TI  - Limitations of the maximum entropy principle in devising drug input rate.
AB  - A computer program applying the principle of maximum entropy to the analysis of
      drug absorption rate has been developed. Plasma concentrations of amoxicillin
      obtained after oral and intravenous dosing have been analysed, together with
      simulated data corresponding to a complex input. Amoxicillin absorption rates
      devised by the program were similar to those obtained by a standard deconvolution
      method, although they were displayed as an almost continuous profile. However,
      improbable fluctuations were obtained with some data sets and the fraction
      absorbed was underestimated by 13%. With the simulated data, the maximum entropy
      program did not provide a better solution than the standard deconvolution
      procedure, and it was sensitive to the addition of random error and to the number
      of samples. The maximum entropy principle, as implemented in our computer
      program, may not have a better performance than standard deconvolution
      procedures, especially in human experiments where the number of blood samples is
      usually limited.

PMID- 8751034
TI  - Pharmacokinetics of thiopental after single and multiple intravenous doses in
      critical care patients.
AB  - Thiopental was administered to neurosurgical patients for cerebral protection and
      its pharmacokinetic parameters were determined after a single bolus of 540, 1000
      or 1500 mg (3 subjects) or after multiple doses of 250 mg (5 subjects) and 500 mg
      (2 subjects) every two hours for up to 7 days. The data were analysed by a two-
      or three-compartment model and linear kinetics. After a single iv bolus, the mean
      initial volume of distribution (V1) was 0.481 l.kg-1, and the steady-state volume
      of distribution (Vss) was 2.16 l.kg-1. The distribution (t1/2 alpha) and
      elimination (t1/2 beta) half-lives were 0.590 and 5.89 h, respectively, and the
      mean residence time (MRT) was 7.44 h. The clearance was 5.41 ml.min-1.kg-1. With
      repeated injections, the pharmacokinetic parameters for each patient were
      estimated taking into account all administered doses and blood samples, which
      were taken whenever possible daily at steady state and after the last dose. The
      variability observed in the pharmacokinetic parameters of thiopental reflected by
      the coefficient of variation (CV%) was wide but was of similar magnitude within
      patients (CVintra) as it was between patients (CVinter). The steady-state trough
      plasma concentration (Cmin obs) ranged from 4.8 to 30 mg.l-1 (mean 16.0 mg.l-1
      and median 14.3 mg.l-1). Peak concentrations (Cmax obs) ranged from 8.35 to 45
      mg.l-1 (25.4 mg.l-1, and median 23.3 mg.l-1). The values of V1 and Vss were
      similar to those obtained after a single dose. For V1, the mean was 0.333 l.kg-1.
      The mean Vss was 2.68 l.kg-1, with a CVintra of 12.6 to 56% and a CVinter of
      13.2%. A shorter distribution half-life t1/2 alpha was noted on multiple dosing;
      the mean value was 0.122 h. The elimination half-life t1/2 beta and the mean
      residence time became longer due to a decrease in clearance. For t1/2 beta the
      mean value was 16.3 h. The mean MRT was 21.9 h, CVintra 9.19 to 48.5%, and the
      CVinter 35.3%. The mean clearance was 2.16 ml.min-1.kg-1, CVintra 7.28 to 25.5%,
      and the CVinter 20.4%. This value is 50% lower than after a single dose.
      Identification of the kinetic parameters of thiopental allows simulation of the
      effects of doses on subsequent plasma levels and will permit a priori prediction
      of day to day adjustment of drug dosage.

PMID- 8751036
TI  - Transplacental transport of netobimin metabolites in ewes.
AB  - Neither netobimin (NTB) nor its metabolite albendazole (ABZ) were found in plasma
      after an oral administration of 20 mg/kg of NTB to pregnant ewes during the last
      third of gestation. ABZ metabolites, albendazole sulphoxide (ABZSO) and
      albendazole sulphone (ABZSO2) were found in plasma 30 min and 2 h, respectively,
      after administration. The maximal plasma concentration (Cmax) of ABZSO was
      detected at 11.6 +/- 1.0 h and for ABZSO2 at 16.5 +/- 2.3 h. The plasma levels of
      the latter remained constant for 36 h, and decreased as ABZSO was removed from
      the blood. Jugular plasma levels of both metabolites did not differ significantly
      from those observed in the ovarian vein, suggesting that there were no exchanges
      between foetal and placental tissues. Both metabolite concentrations were similar
      in the umbilical vein and artery and in the amniotic and allantoic fluids, their
      values were half the maternal plasma concentration, leading to the conclusion
      that there was transplacental movement of metabolites. Both metabolites reached
      the foetus and could be responsible for the teratogenicity of NTB in sheep.

PMID- 8751037
TI  - Theophylline pharmacokinetics and metabolism in rabbits following single and
      repeated administration of Capsicum fruit.
AB  - Pharmacokinetics and metabolism of theophylline were studied in three groups of
      male rabbits, after intravenous administration (12 mg/kg), with and without oral
      ground Capsicum fruit suspension. Compared with control values, plasma
      theophylline half-life of distribution and of elimination, areas under plasma
      curves, clearance and volume of distribution did not show any significant
      difference. On the contrary, the elimination rate constant (k1,0) is
      significantly different (0.01 < P < 0.05) after a single dose of capsicum and
      remained unchanged after a repeated dose. Concerning the metabolism of
      theophylline in rabbits, the results showed that the oral administration of a
      single dose of Capsicum fruit suspension does not significantly affect the
      urinary excretion of theophylline and its metabolites--1,3-dimethyluric acid (1,3
      DMU) and 1-methyluric acid (1-MU). On the other hand, after a repeated dose of
      Capsicum fruit for 7 days, the quantity of 1-MU was significantly reduced (0.01 <
      P < 0.05). In conclusion, it was found that a single dose of Capsicum fruit could
      affect pharmacokinetic parameters of theophylline (k1,0), while a repeated dose
      affected the metabolic pathway of xanthine oxidase.

PMID- 8751038
TI  - Effects of capsaicinoids on oxidative metabolism of caffeine in isolated rat
      hepatocytes.
AB  - The metabolism of caffeine was studied in isolated rat hepatocytes, in the
      absence and presence of capsaicinoids. Caffeine and four primary metabolite
      fractions were identified by high performance liquid chromatography: 1,7
      dimethylxanthine, 3,7-dimethylxanthine, 1,3-dimethylxanthine and 1,3,7
      trimethyluric acid. The incubation with the lowest concentrations (0.1 and 1
      microM) of capsaicinoids (natural extract, capsaicin, dihydrocapsaicin) showed a
      stimulatory effect on caffeine metabolism, which was further enhanced with
      capsaicin. At 10 microM, capsaicin stimulated the two pathways of metabolism of
      caffeine (N-demethylation and C-8 oxidation). In contrast, dihydrocapsaicin and
      the natural extract seem to inhibit the N-demethylation pathways without
      affecting the C-8 oxidation route. The inhibitory activity on the N-demethylation
      pathways and especially the N-7 demethylation pathway was pronounced at the first
      30 min of incubation. These results suggest that the two pathways (N
      demethylation and C-8 oxidation) are mediated by different isozymes of
      cytochromes P-450. This is in agreement with recent findings.

PMID- 8751039
TI  - Effect of the aluminium ion on hepatic elimination of quinine and quinidine.
AB  - A study of the influence of the aluminum ion on the blood and hepatic kinetics of
      two alkaloid stereoisomers--quinine and quinidine--after their p.o. and s.c.
      administration (80 mg/kg) to rats was carried out. It appeared that the mode of
      application of the stereoisomers had different effects on their resorbtion in
      control animals. In the case of s.c. application, blood concentrations of quinine
      in some time intervals reached significantly higher levels than those found for
      quinidine. Hepatic elimination of quinine appeared to be independent of the mode
      of its application, whereas the elimination of quinidine was significantly
      increased after its s.c. application. Pretreatment of rats with aluminium
      chloride (600 mg/kg, i.p.) 2 h before injecting one of the stereoisomers had a
      different effect on their concentrations in blood, and significantly higher
      effect on their bile elimination. The quinine concentrations in blood after its
      p.o. administration were not changed significantly, but after s.c. application
      these concentrations were increased in some time intervals. The presence of the
      aluminum ion caused a significant increase in the rate of hepatic elimination of
      quinine, whereas it had no significant effect on quinidine elimination.

PMID- 8751040
TI  - Effect of fluvastatin, an inhibitor of 3-hydroxy-3-methyl glutaryl CoA reductase,
      on drug-metabolizing enzymes in rats.
AB  - Fluvastatin (FV), a new cholesterol-lowering agent, has been studied for its
      effects on hepatic microsomal drug-metabolizing enzymes in male rats. FV was
      orally administered in dosages of 1, 5, and 30 mg/kg/day for 7 consecutive days.
      3-Hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activities were markedly
      decreased at all dose levels. The amount of microsomal protein and the contents
      of cytochromes P450 and b5 did not change. No induction of aniline hydroxylase,
      aminopyrine N-demethylase, testosterone hydroxylases (15 alpha-, 7 alpha-, 6 beta
      , 16 alpha-, and 16 beta-), and UDP-glucuronosyltransferase were found. On the
      other hand, 7-ethoxycoumarin o-deethylase activity was slightly increased and
      lauric acid omega-1-hydroxylase activity tended to be decreased after treatment
      with FV.

PMID- 8751041
TI  - Pharmacokinetics of the antiviral agent 3-deazaneplanocin A.
AB  - The pharmacokinetics of 3-deazaneplanocin A (c3Nep), a competitive inhibitor of S
      adenosyl-L-homocysteine (AdoHcy) hydrolase and novel antiviral agent, was
      investigated in female BALB/c mice. Animals were given a single intravenous dose
      of [3H]-c3Nep (0.1 mg/kg; 10 microCi), and blood and selected tissues were
      collected at various intervals thereafter for up to 72 h. The plasma
      concentration versus time data for c3Nep was best approximated by a two
      compartment open model with first order elimination. The elimination half-life
      was 12.8 min, the area-under curve (AUC) was 3.38 micrograms.min.ml-1. The
      distribution of c3Nep into tissues was not extensive. Following 30, 120 min, and
      24 h after dosing, the kidneys and the liver contained the highest amount of
      drug, but this amount did not exceed 1 microgram/g tissue. At these time periods,
      the majority of activity in the tissues represented labeled derivatives of c3Nep
      indicating that this compound was converted to stable metabolites. The presence
      of labeled conversion products in the blood confirmed that this drug is
      metabolized in vivo. The fact that c3Nep bound to plasma proteins in vitro may
      explain this drug's limited tissue distribution. The half-life and tissue
      distribution of c3Nep were different from those of carbocyclic 3-deazaadenosine,
      a related adenosine nucleoside antiviral drug and AdoHcy hydrolase inhibitor.

PMID- 8751042
TI  - Pharmacokinetics of pipecuronium in infants, children and adults.
AB  - In order to explain the reported shorter clinical duration of action of
      cumulative ED95 of pipecuronium in infants as compared to children or adults, the
      pharmacokinetic profiles of pipecuronium were compared in infants (n = 6; mean
      age 6.8 months; mean weight 7.3 kg) in children (n = 6; mean age 4.6 years; mean
      weight 19.2 kg) and in adults (n = 7; mean age 42 years; mean weight 58.2 kg).
      Equipotent doses (2 x ED95) of pipecuronium were injected i.v. as single bolus
      and arterial blood was sampled for 4-5 h. Pipecuronium was quantified by complex
      formation with [125I]-labelled rose bengal. Pharmacokinetic parameters were
      calculated using a two-compartment open model. The median for the distribution
      half-life of pipecuronium was 2.54 min (interquartile range: 1.0-2.5 min) in
      infants and 2.04 min (0.26-2.04 min) in children; both were significantly shorter
      than in adults (5.75 [3.7-9.7] min). The plasma clearance of pipecuronium was
      significantly decreased in infants (1.50 [0.6-1.5] ml.min-1.kg-1; P < 0.05) as
      compared to children and adults (2.27 [0.88-2.27] and 2.45 [1.7-3.2] ml.min-1.kg
      1, respectively). The total volume of distribution was similar in all three
      groups. We conclude that the pharmacokinetic features of pipecuronium are age
      dependent: differences as compared to adults consisted of a faster distribution
      in both infants and children and a slower elimination in infants. The
      pharmacokinetic profile of pipecuronium does not explain the faster recovery from
      neuromuscular blockade in infants as compared to children. Because of the low
      total plasma clearance in infants, pipecuronium dosage should be carefully
      monitored to avoid accumulation and prolonged paralysis.

PMID- 8751043
TI  - Non-linear renal and biliary clearances of antiviral polyoxometalates in rats.
AB  - The polyoxometalates, JM 1591 (K12H2[P2W12O48].24 H2O), JM 1596
      (K10[P2W18Zn4(H2O)2O68].20 H2O), and JM 2820 ([Me3NH]8[Si2W18Nb6O77]) have been
      shown to have potent activity against HIV-1 and HIV-2. The pharmacokinetics of JM
      1591, JM 1596 and JM 2820 after intravenous administration of 50 mg/kg were
      investigated in rats. Renal and biliary clearances of the three compounds were
      found to be dependent on unbound plasma polyoxometalate concentration. Computer
      modeling was performed by fitting nonlinear pharmacokinetic models simultaneously
      to unbound plasma concentration, urinary excretion rate and biliary excretion
      rate versus time data. The renal clearances of JM 1591 and JM 2820 were described
      by glomerular filtration, saturated active tubular secretion at all plasma
      concentrations observed and saturable active tubular reabsorption. The urinary
      excretion of JM 1596 was characterized by glomerular filtration, saturable active
      tubular secretion and apparent linear reabsorption. Biliary clearances of all
      three polyoxometalates were described by a Michaelis-Menten function.

PMID- 8751044
TI  - Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17 beta
      estradiol.
AB  - Naringenin, quercetin and kaempferol, which may be found in glycoside form in
      natural compounds such as grapefruit, are potent inhibitors of cytochrome P-450
      metabolism. The influence of these flavonoids on the metabolism of 17 beta
      estradiol was investigated in a microsome preparation from human liver. The
      flavonoids were added in concentrations of 10, 50, 100, 250 and 500 mumol/l to
      the microsome preparation. The metabolism of 17 beta-estradiol was concentration
      dependently inhibited by all the flavonoids tested. Addition of the flavonoids to
      the microsome preparation did not influence estrone formation, while a potent
      inhibition of estriol formation was observed. At the highest concentrations
      tested of the respective flavonoid, there was approximately 75-85% inhibition of
      estriol formation. However, naringenin was a less potent inhibitor of 17 beta
      estradiol metabolism as compared to quercetin and kaempferol. The most likely
      mechanism of action of the flavonoids on 17 beta-estradiol metabolism is
      inhibition of the cytochrome P-450 IIIA4 enzyme, which catalyzes the reversible
      hydroxylation of 17 beta-estradiol into estrone and further into estriol. These
      hydroxylation processes represent the predominant steps of the hepatic metabolic
      conversion of endogenous as well as exogenous 17 beta-estradiol. This interaction
      would be expected to inhibit the first-pass metabolism of 17 beta-estradiol, and
      this has recently been demonstrated after oral administration of 17 beta
      estradiol to women.

PMID- 8751047
TI  - The Leiden/Amsterdam center for drug research.

PMID- 8751045
TI  - Kinetics and metabolism of 2-chloro-2'-deoxyadenosine and 2-chloro-2'-arabino
      fluoro-2'-deoxyadenosine in the isolated perfused rat liver.
AB  - 2-Chloro-2'-deoxyadenosine (CdA), a newly developed anticancer drug, has been
      tested in phase II trials in the treatment of lymphoproliferative disorders. 2
      Chloro-2'-arabino-fluoro-2'-deoxyadenosine (CAFdA), an acid stable derivative of
      CdA with promising anti-lymphoproliferative activity, has been suggested as a
      potentially effective oral drug. In the present study, we investigated the
      metabolism of CdA and CAFdA in isolated perfused rat liver. The liver was
      recycled with a perfusate containing CdA or CAFdA (2-200 micrograms/ml) for 3.5
      h. The elimination half-lives were concentration-dependent for both CdA and
      CAFdA. The elimination rate of CAFdA was slower than that of CdA, suggesting that
      CAFdA is more stable than CdA against deglycosylation by hepatic enzymes. The
      amount of 2-chloroadenine (CAde), the major metabolite of CdA and CAFdA,
      increased proportionally with time and dose. The first passage effect was
      approximately 50% both for CdA and CAFdA. Less than 1% of CdA and CAFdA were
      recovered as intact drug in the bile during the experiment and less than 1% of
      CdA and 0.1% of CAFdA were found as CAde in the bile, respectively. The
      structural identity of metabolites present in the perfusates was verified
      utilizing electrospray ionization mass spectrometry.

PMID- 8751046
TI  - Disposition of a new rate-controlled formulation of prazosin in the treatment of
      hypertension during pregnancy: transplacental passage of prazosin.
AB  - Prazosin (PRZ) in conventional tablet form (P-CT) has the disadvantages of a
      relatively short terminal half-life, a slight solubility in water and the well
      recognized adverse effect of symptomatic orthostatic hypotension. The
      pharmacokinetic study of a new rate-controlled formulation of prazosin (Prazosin
      Gastrointestinal System: P-GS) was performed in 9 pregnant women during the third
      trimester of pregnancy. Patients had persistent elevation of blood pressure. The
      subjects gave their informed consent for oral administration of 1 daily dose of 5
      mg P-GS at 8 a.m. A first analysis period on day 1 enabled definition of the
      initial pharmacokinetic behavior of the drug, while the aim of a second was to
      evaluate its fate at plateau. The clinical course of both mother and fetus was
      subsequently monitored. This was an open, non-randomized study, each patient
      serving as her own control. For 3 patients, we aimed to determine the possible
      transplacental passage of PRZ at delivery. PRZ levels were measured by HPLC and
      data were analysed by noncompartmental linear pharmacokinetic methods. The data
      show: (i) P-GS was well tolerated by all patients and there were no significant
      changes in fetal heart rate during the study. (ii) A significant decrease in
      diastolic blood pressure was observed after the 36th hour following the first
      dose of P-GS while a reduction in systolic blood pressure was observed on day 4.
      (iii) An approximated relative bioavailability (f'P-GS) of 36.5% was calculated.
      P-GS appears to have a lower bioavailability than P-CT in women of similar
      gestational age. (iv) Both Cmax and AUC0-->infinity are significantly increased
      at plateau. Further, terminal half-life is increased with regard to the value
      determined with P-CT. No accumulation of PRZ was noted at steady-state. (v) P-GS
      is an example of an oral zero-order absorption product that offers one approach
      to control and improve the outcome of hypertensive therapy during pregnancy. This
      treatment could represent an alternative to methyldopa as a first treatment of
      pregnancy-associated hypertension. (vi) There is a slight transplacental passage
      of the drug (of the order of 10-20%).

PMID- 8751048
TI  - AIDS-like disease following mucosal infection of pig-tailed macaques with
      SIVsmmPBj14.
AB  - Following exposure of the rectal or vaginal mucosa to cell-free SIVsmmPBj14, four
      male and two female pig-tailed macaques developed a characteristic acute disease,
      including mucoid diarrhea, lymphopenia, and anorexia. Two macaques infected by
      the rectal route died within 14 days, and one female died of an AIDS-like disease
      at five months after inoculation. The three other animals have survived more than
      nine months, but all are exhibiting lymphadenopathy, thrombocytopenia, and
      progressive declines in percentages and numbers of CD4+ lymphocytes.

PMID- 8751049
TI  - Isolation and characterization of the first simian immunodeficiency virus from a
      feral sooty mangabey (Cercocebus atys) in West Africa.
AB  - The lineage of HIV-2-like viruses was studied in feral sooty mangabeys (SMs) by
      serological and genetic methods. Four feral sooty mangabeys were positive for
      simian immunodeficiency virus (SIV) antibodies and a new isolate, SIVsmSL92a, was
      obtained. Genetic analysis of gag genes showed that SIVsmSL92a was highly diverse
      and a distinct sequence subtype within the SIV sm/HIV-2 family. The results
      showed that SIVsm is the most diverse group of SIVs found thus far in a single
      monkey species.

PMID- 8751050
TI  - Origins of simian immunodeficiency virus infection in macaques at the New England
      Regional Primate Research Center.
AB  - A cohort of rhesus macaques (Macaca mulatta), obtained from the California
      Regional Primate Research Center (CRPRC) and necropsied in 1970-72 with lesions
      suggestive of simian immunodeficiency virus (SIV) infection, was identified at
      the New England Regional Primate Research Center (NERPRC). Polymerase chain
      reaction (PCR), DNA sequence analysis, and in situ hybridization were used to
      confirm the presence of SIV nucleic acids. This represents the earliest case of
      SIV infection at the NERPRC and suggests a common source for present day SIV
      isolates.

PMID- 8751051
TI  - VCAM-1 expression and leukocyte trafficking to the CNS occur early in infection
      with pathogenic isolates of SIV.
AB  - This study reports on the endothelial expression of vascular cell adhesion
      molecule-1 (VCAM-1) in the central nervous system (CNS) early after experimental
      infection of rhesus monkeys (Macaca mulatta) with pathogenic and nonpathogenic
      simian immunodeficiency virus (SIV). Diffuse endothelial expression of VCAM-1 was
      observed in the CNS in all animals receiving pathogenic SIV. These findings
      demonstrate the rapidity with which pathogenic SIV is able to enter the CNS and
      induce endothelial cell activation.

PMID- 8751053
TI  - Assessing genetic-based therapies for AIDS using the simian immunodeficiency
      virus.
AB  - A plasmid encoding the full-length infectious molecular proviral clone of
      SIVmac239 was generated. Virus derived from cells transfected with this clone
      replicated to high levels and was cytopathic for some transformed human CD4+ cell
      lines and primary rhesus macaque peripheral blood mononuclear cells. Since
      replication of SIV requires the functional expression of the viral encoded rev
      protein, transient co-transfection studies were initiated with the infectious
      proviral clone and a well-characterized trans-dominant negative HIV-1 rev mutant.

PMID- 8751052
TI  - Differences in viral distribution and cell adhesion molecule expression in the
      intestinal tract of rhesus macaques infected with pathogenic and nonpathogenic
      SIV.
AB  - We investigated SIV infection and expression of adhesion molecules in the small
      intestine of rhesus macaques infected with pathogenic SIV (SIVmac) or
      nonpathogenic clone (SIV1A11). There was a wider dissemination and marked
      difference in tissue localization of SIVmac relative to SIV1A11. Our results also
      indicate that viral pathogenicity is associated with increased migration of
      inflammatory cells expressing VLA-alpha 4, LFA-1 alpha, Mac-1 alpha, ICAM-1, and
      beta 2 integrin into the intestinal mucosa.

PMID- 8751054
TI  - Neutralising epitopes of simian immunodeficiency virus envelope glycoprotein.
AB  - Monoclonal and polyclonal antibodies with weak SIV neutralising activity bind to
      the V2 and V4 regions of gp120 or bind to the amino acids DWNND in gp41.
      Antibodies with the most potent neutralising activity recognise conformation
      dependent epitopes involving the V3 and V4 regions of gp120. Monoclonal
      antibodies that map to the V3 region of SIVmac failed to neutralise. However, one
      antibody to SIV AGM neutralised but only in the presence of soluble CD4.

PMID- 8751055
TI  - Fourth annual survey of worldwide HIV, SIV, and SHIV challenge studies in
      vaccinated nonhuman primates.

PMID- 8751056
TI  - Distribution of vestibulospinal synaptic input to cat triceps surae motoneurons.
AB  - We applied supramaximal, repetitive stimulation to the lateral vestibular nucleus
      (Deiters' nucleus, DN) at 200 Hz to evoke stead-state synaptic potentials in
      ipsilateral triceps surae motoneurons of the cat. The effective synaptic currents
      underlying these potentials were measured using a modified voltage-clamp
      technique. The steady-state effective synaptic currents evoked by activating DN
      were generally small and depolarizing (mean 2.5 +/- 2.6 nA). DN stimulation
      generated hyperpolarizing synaptic currents in 2 of the 34 triceps motoneurons
      studied. The effective synaptic currents from DN tended to be larger in putative
      type F motoneurons than in putative type S cells (type F mean 3.0 +/- 3.1 nA;
      type S mean 1.8 +/- 1.0 nA). There was a statistically significant difference
      between the inputs to putative type FF and putative type S motoneurons (mean
      difference 2.8 nA, t = 2.87, P < 0.01). The synaptic input from DN to medial
      gastrocnemius motoneurons had approximately the same amplitude as that from
      homonymous Ia afferent fibers. However, the distribution of DN input with respect
      to putative motor unit type was the opposite of that previously reported for Ia
      afferent input. Thus, the synaptic input from DN might act to compress the range
      of recruitment thresholds within the motoneuron pool and thereby increase the
      gain of its input-output function.

PMID- 8751057
TI  - Oxytocinergic innervation to the upper thoracic sympathetic preganglionic neurons
      in the rat. A light and electron microscopical study using a combined retrograde
      transport and immunocytochemical technique.
AB  - A combination of retrograde cell body labeling and immunohistochemistry was
      employed to elucidate how oxytocinergic fibers make contact with sympathetic
      preganglionic neurons (SPNs) in the rat spinal cord from T1 to T4. SPNs were
      labeled retrogradely using cholera toxin subunit B (CTb) or horseradish
      peroxidase-conjugated CTb. Oxytocin-immunoreactive (ir) fibers were found in the
      intermediate zone, including the sympathetic preganglionic subnuclei. In the
      central autonomic nucleus and the intercalated nucleus, brown-stained oxytocin-ir
      varicosities or terminals were frequently observed to stud black-stained
      dendrites of SPNs. Electron microscopical observations showed that oxytocin-ir
      terminals form synapses with dendrites or soma of the sympathetic preganglionic
      neurons. The terminals contained numerous small clear round vesicles and a few
      large, cored vesicles. These results clearly show that a large proportion of SPNs
      are innervated by oxytocin-containing fibers. The origin of these fibers is
      discussed, and it is concluded that they are probably descending fibers from the
      paraventricular nucleus of the hypothalamus.

PMID- 8751058
TI  - Vestibular responses of flocculus and vestibular nuclei neurons in mice (B6CBA).
      Variation of stimulus amplitude and frequency.
AB  - Vestibular nuclei (Vn) neurons and floccular Purkinje (P) cells of unanesthetized
      paralyzed mice (B6CBA) responding to horizontal angular acceleration in the dark
      (type I and type II neurons) were studied by extracellular recordings with
      micropipettes while varying either the frequency (and velocity) or the amplitude
      (and velocity) of the sinusoidal rotation, keeping the respective third parameter
      constant. Phase and sensitivity were analyzed by a Fourier analysis and a "best
      sine fitting" program. Recording sites were localized by means of small
      iontophoretically applied horseradish peroxidase markings. The neuronal response
      amplitude at fundamental frequency (determined from peristimulus time histograms)
      increased with the frequency and amplitude of the sinusoidal rotation for both Vn
      and floccular neurons (0.05-0.5 Hz; +/- 60 degrees amplitude). Stimulus
      frequency/response amplitude and stimulus amplitude/response amplitude curves of
      floccular neurons were distinctly lower in magnitude than those of Vn neurons (P
      < 0.01) Accordingly, the sensitivity (re velocity) curves of Vn neurons and P
      cells differed in magnitude significantly (decreasing slightly with increasing
      stimulus frequency and amplitude in Vn neurons and more or less independent of
      stimulus parameters in floccular P cells). Response amplitudes of type I and type
      II neurons did not differ from each other. Phase advance relative to head angular
      velocity in the midfrequency range in Vn neurons was very small, indicating a
      head velocity signal carried by the Vn neurons. In floccular P cells phase
      advance was only small at 0.1 Hz (amplitude +/- 35 degrees), but increased with
      augmenting frequency to 140 degrees at 0.5 Hz. With a constant stimulus frequency
      (0.3 Hz) and varied stimulus amplitude, phase advance was 90 degrees at +/- 20
      degrees amplitude and 60 degrees amplitude. Data are shown for the first time in
      which both the stimulus frequency and the stimulus amplitude have been varied in
      the same species and in the same neurons. The results demonstrate that the single
      data are in general well within the range of those found in other species, but
      they demonstrate further that phase behavior is dependent on the stimulus
      paradigm. The data provide the basis for comparative studies with mutant mice.

PMID- 8751059
TI  - Responses of flocculus and vestibular nuclei neurons in Weaver mutant mice (B6CBA
      wv/wv) to combined head and body rotation.
AB  - The responses of vestibular nuclei (Vn) neurons and floccular Purkinje (P) cells
      to natural stimulation of the horizontal canals were recorded in paralyzed Weaver
      mutant mice. The Weaver mice suffer from an almost complete postnatal
      degeneration of granule cells and a portion of the P cells (Sidman et al. 1965).
      Parallel fibers are never elaborated (Bradley and Berry 1978). Recording sites
      were localized by means of small, iontophoretically applied HRP markings. Phase
      and sensitivity were analyzed by a Fourier analysis and a "best sine fitting"
      program. As in the normal "control" mice (Grusser-Cornehls et al. 1995), the
      "simple spike" discharges of Vn and P cells in Weaver mutant mice are modulated
      sinusoidally upon sinusoidal stimulation. The neuronal response amplitude at
      fundamental frequency (determined from peristimulus time histograms, PSTHs
      increased with frequency (0.05-0.5 Hz) for both Vn and floccular neurons. The
      stimulus frequency/response amplitude and sensitivity (re velocity) curves for
      floccular neurons are distinctly lower in magnitude than those of Vn neurons (P <
      0.01). In our sample of neurons, the Vn neurons curves of the mutants display a
      remarkable be behavior: the mean value curve of type I neurons is shifted upward,
      indicating a loss of inhibition but that of type II, downward, demonstrating a
      downregulation in comparison with the control values. The difference between the
      two curves is statistically significant (P < 0.001). The mean value curve of all
      mutant Vn neurons depends on the different fractions of type I and type II
      neurons in the sample investigated. In our investigations, the mean value curves
      of both type I and type II neurons also exceed those of the normal controls. The
      phase shift relative to head angular velocity in the midfrequency range in Vn
      neurons was very similar to that in normal controls, but the phase advance in the
      range of 0.3-0.5 Hz was somewhat larger and the SD larger over the whole range
      tested. Concerning the phase relationship for floccular neurons, a major
      difference occurred in contrast to the normal controls: the phase lead and phase
      lag varied from neurons to neuron, in individual neurons from frequency to
      frequency, and in some neurons distinctly from trial to trail. It is hypothesized
      that an intact mossy fiber-granule cell-parallel fiber system plays an important
      role in an orderly information flow, transmitted through the P-cell axons, and
      that the morphological disruption has implications for target cell activity.
      There is a strong suggestion that the diverse behavior of type I and type II
      neurons in the Vn may have implications for the poor motor performance in Weaver
      mutant mice.

PMID- 8751061
TI  - Antibody-mediated lysis of the bovine subcommissural organ maintained in culture.
AB  - The subcommissural organ (SCO) is a brain gland that secretes glycoproteins into
      the cerebrospinal fluid (CSF). It is an ancient and conserved secretory structure
      of the brain, developing very early in ontogeny. However, the function of the SCO
      is unknown. The secretory cells of the SCO are arranged into a single or double,
      irregularly shaped layer located at the interface of the CSF and nervous tissue.
      This has prevented its selective surgical destruction. The present investigation
      was designed to destroy the secretory cells of 30-day-old explants of bovine SCO
      by use of an immunological approach. A membrane preparation enriched with plasma
      membrane of the secretory cells of the bovine SCO was obtained. This preparation
      was further processed to separate the structural proteins. A similar procedure
      was applied to obtain a fraction of integral proteins of the plasma membrane of a
      nonsecretory ciliated ependyma. Antisera were prepared against both preparations
      of integral proteins. The antiserum against the fraction obtained from the SCO
      cells immunostained the plasma membrane of the bovine SCO cells and in immunoblot
      it reacted with several proteins of the membrane preparation from SCO cells. When
      added to the culture medium this antibody bound to the apical plasma membrane of
      the secretory ependyma of the bovine SCO kept in culture; it caused the lysis of
      these cells when used together with complement. None of these properties were
      displayed by the antiserum raised against the integral proteins of the plasma
      membrane of the ciliated ependyma. This antiserum, however, immunostained the
      bovine ciliated ependyma neighboring the SCO. These results indicate that
      immunological surgery of the SCO in living animals may be possible to achieve.

PMID- 8751060
TI  - Distribution of Fos-like immunoreactivity in the caudal medullary reticular
      formation following noxious facial stimulation in the rat.
AB  - To investigate the topographic organization of nociceptive neurons in the caudal
      medullary reticular formation, the distribution of cells that exhibit c-fos
      expression was examined following a unilateral noxious facial stimulus:
      subcutaneous injection of formalin into the vibrissal pad of awake rats.
      Labelling for Fos-like immunoreactivity was present in a somatotopic distribution
      in a region of the lateral reticular formation adjacent to trigeminal nucleus
      caudalis, which corresponds approximately to lamina V of the medullary dorsal
      horn. Labelling in adjacent regions of the reticular formation showed no
      somatotopy but was predominantly ipsilateral. Contralateral labelling was
      concentrated ventrolaterally around the lateral reticular nucleus and dorsally
      near the nucleus of the solitary tract.

PMID- 8751062
TI  - Repeated administration of a selective dopamine D2 receptor agonist to 6-OHDA
      lesioned rats does not affect the survival and outgrowth of intrastriatal fetal
      mesencephalic grafts.
AB  - The objective of the present study was to investigate the effects of chronic
      activation of dopamine D2 receptors on the development of grafted fetal rat
      mesencephalic dopaminergic neurons. Therefore, unilaterally 6-hydroxydopamine -
      lesioned rats received intrastriatal mesencephalic cell suspension grafts and
      were subsequently chronically treated with the selective dopamine D2 receptor
      agonist LY 171555 (Quinpirole). After treatment for 6 consecutive weeks, the rats
      were processed for tyrosine-hydroxylase immunocytochemistry to assess the
      survival and outgrowth from grafted dopaminergic neurons. morphological analysis
      revealed that, like the volume and morphology of the graft, neither the number
      nor the cell area of grafted dopaminergic neurons was significantly different
      between vehicle- and LY 171555-treated animals. To obtain a quantitative estimate
      of the graft-derived dopaminergic reinnervation, a computerized image analysis
      system was used. Using this procedure, which was based on the densitometric
      measurement of tyrosine hydroxylase immunoreactivity in the area adjacent to the
      grafted tissue, it was found that the extent of graft-derived outgrowth also
      appeared to be unaffected upon chronic treatment with LY 171555. It is concluded
      that long-term concurrent administration of a dopamine D2 receptor agonist for 6
      consecutive weeks does not impair the survival and outgrowth of grafted rat fetal
      mesencephalic dopaminergic neurons.

PMID- 8751064
TI  - A metric for assessing acuity in positioning joints and limbs.
AB  - In this paper, we present a method for assessing the exactness of sensing and
      setting the positions of joints and limbs, using a measure we call target
      resolution. Target resolution, derived from information theory but ultimately
      based on variance, estimates the fewest number of discrete, equally spaced
      targets required within a range to provide the maximum possible information
      transfer from any target set. We argue that target resolution provides better
      insight into the exactness of position sense than does the usual measure of
      accuracy based on mean or constant error. Studies have shown that measures of
      mean error in setting or indicating positions of joints or limbs exhibit
      lability; they drift and show considerable sensitivity to factors such as
      previous positions of the limb and learning. We derive the equation for
      calculating target resolution and give example resolutions for several joints we
      have tested. Target resolution often gives a quite different impression of
      proprioceptive exactness than do measures of accuracy based on mean error.

PMID- 8751063
TI  - Synaptic interactions involving acetylcholine, glutamate, and GABA in rat
      auditory cortex.
AB  - Using electrophysiological techniques in the in vitro rat auditory cortex, we
      have examined how spontaneous acetylcholine (ACh) release modifies synaptic
      potentials mediated by glutamate and gamma-aminobutyric acid (GABA). Single
      stimulus pulses to lower layer VI elicited in layer III a four-component (A-D)
      extracellular field response involving synaptic potentials mediated by glutamate
      and GABA. The cholinesterases inhibitor eserine (10-20 microM) or the cholinergic
      agonist carbachol (25-50 microM) depressed by 10-50% the glutamatergic components
      A and C, and the GABAergic components B and D. Atropine reversed the depressive
      effects of eserine and carbachol. A novel finding was that the degree of
      depression of component A varied inversely with stimulus intensity. However,
      during partial pharmacological antagonism of GABAA receptors, depression of A
      varied directly, not inversely, with stimulus intensity. Normally, then,
      depression of A is offset by reduced GABAergic inhibition of A. We also tested
      for differential depression of responses mediated by N-methyl-D-aspartate (NMDA)
      versus non-NMDA glutamate receptors. Following physiological and pharmacological
      isolation of the responses, eserine depressed the non-NMDA, but not the NMDA,
      receptor-mediated potential. Since the isolated NMDA potential still could be
      depressed by carbachol, the data suggested that activation of NMDA receptors may
      reduce spontaneous ACh release. In support of this, preincubation of slices in
      NMDA (10-20 microM) largely prevented eserine's, but not carbachol's, depression
      of components A and B. These results permit three conclusions of relevance to
      cortical information processing: (1) spontaneous ACh release tonically depresses
      synaptic potentials mediated by glutamate and GABA; (2) ACh depresses responses
      to weak inputs to a greater degree than responses to strong inputs: (3)
      activation of NMDA receptors may "feedback" to reduce ACh release, a mechanism
      that could place regulation of local ACh release under glutamatergic afferent
      control.

PMID- 8751065
TI  - Long-lasting depression of motor-evoked potentials to transcranial magnetic
      stimulation following exercise.
AB  - We used transcranial magnetic stimulation to study the modulation of motor cortex
      excitability after rapid repetitive movements. Eleven healthy subjects aged 24-32
      years were evaluated. Serial motor-evoked potential (MEP) recordings were
      performed from the right thenar eminence every 5 min for a period of 20 min at
      rest and for a period of 35 min after repetitive abduction-adduction of the thumb
      at maximal frequency for 1 min. All subjects presented distinct changes in MEP
      amplitude after exercise with an approximately 55% mean maximal decrease compared
      with basal conditions and complete recovery 35 min after the end of the exercise.
      The time course of MEP amplitude changes presented the following trend: (1) a
      rapid decrease phase within the first 5 min; (2) a maximal depression phase of 10
      min duration (from the 5th to the 15th min); and (3) a slow recovery phase. No
      significant modifications in post-exercise MEP amplitude were found in
      ipsilateral non-exercised muscles. In order to determine the level where these
      changes take place, we recorded the M and F waves induced by median nerve
      stimulation at the wrist (all subjects) and MEPs in response to transcranial
      electrical stimulation (five subjects) at rest and during the decrease and
      maximal depression phases. None of these tests were significantly affected by
      exercise, indicating that the motor cortex was the site of change. Evaluation of
      maps of cortical outputs to the target muscle, performed in four subjects, showed
      an approximately 40% spatial reduction in stimulation sites evoking a motor
      response during the maximal depression phase. These data prove that exercise
      induces a reversible, long-standing depression of cortical excitability, probably
      related to intracortical presynaptic modulation, which transitorily reduces the
      motor representation area.

PMID- 8751066
TI  - Qualitative discrepancies between trunk muscle activity and dynamic postural
      requirements at the initiation of reaching movements performed while sitting.
AB  - Reaching movements are associated with widespread, nonfocal muscle activity. That
      activity is often assumed to play a postural role. We tested this assumption for
      the trunk muscles at the initiation of reaching movements with the following
      question. Does initial trunk muscle activity play a dynamic postural role by
      resisting the segmental interactive effects of the arm movement on the trunk?
      Seated subjects performed bilateral reaching movements while target direction was
      systematically varied. Muscle activity was recorded from flexors and extensors of
      the trunk and shoulder. Trunk muscle activity was compared with trunk torques
      calculated from simulations of reaching movements in which the trunk was modeled
      to stay still. Recorded trunk muscle activity was in qualitative agreement with
      torque predictions for only some target directions, suggesting that the target
      directions to counteract postural disturbances at the initiation of reaching
      movements.

PMID- 8751067
TI  - Contralateral and long latency effects of human biceps brachii stretch reflex
      conditioning.
AB  - Results from previous studies on monkeys and human subjects have demonstrated
      that the biceps brachii spinal stretch reflex (SSR) can be operantly conditioned.
      The extent to which conditioning paradigms influence contralateral SSRs or longer
      latency responses in the same limb has not been examined. Nine subjects were
      given 10 training sessions to either increase or decrease the size of their
      biceps brachii SSR. Group changes were compared to the mean of six baseline
      (control) sessions. Both groups showed progressive SSR changes over the training
      sessions. Up-trained subjects increased their SSR responses by an average of
      135.3% above baseline, with the last three sessions showing a 237.5% increase,
      while down-trained subjects reduced their average SSR responses by 43.4%, with a
      52.7% reduction over the last three sessions. ipsilateral longer latency
      responses showed average changes of 68.9% and -68.7% for up- and down-trainers,
      respectively. As in the case of SSRs, these responses changed progressively over
      sessions, with a 131.5% increase seen in the last three up-training sessions and
      an 82.4% reduction over the same period for down-trainers. Correlation
      coefficients between SSR and longer latency responses were high (R = 0.90, up
      trainers; R = 0.87, down-trainers). Contralateral SSR and longer latency
      responses, measured in the absence of feedback and at least 10 min after
      ipsilateral conditioning, showed directional changes that were similar to the
      trained side, but their magnitudes were not as profound. Collectively, these data
      suggest that unilateral SSR conditioning affects spinal circuits controlling
      contralateral SSRs and influences longer latency responses.

PMID- 8751068
TI  - A quantitative study of auditory-evoked saccadic eye movements in two dimensions.
AB  - We investigated the properties of human saccadic eye movements evoked by acoustic
      stimuli in the two-dimensional frontal plane. These movements proved to be quite
      accurate, both in azimuth and in elevation, provided the sound source spectrum
      had a broad bandwidth and a sufficiently long duration. If the acoustic target
      was a tone, the azimuth of the saccadic end points remained equally accurate,
      whereas the elevation of the response was related to the frequency of the tone,
      rather than to the physical position of the target. Saccade elevation accuracy
      also declined substantially for short-duration noise bursts, although response
      elevation remained highly correlated with target elevation. The latencies of
      auditory saccades depended on the amplitude, but not on the direction of the eye
      movement, suggesting a polar coordinate origin of auditory saccade initiation. We
      also observed that the trajectories of auditory saccades were often substantially
      curved. Both a qualitative and a model-based analysis showed that this curvature
      corrected for errors in the initial direction of the saccade. The latter analysis
      also suggested that the kinematic properties of auditory saccades could be
      described by the superposition of two overlapping saccadic eye movements,
      hypothesized to be based on binaural difference cues and monaural spectral cues
      in the auditory signal, respectively. It is argued that, although the audio
      oculomotor system has to operate in a feedforward way, it must nevertheless have
      access to an accurate representation of actual and desired eye position.
      Different models underlying the generation of auditory saccades are discussed.

PMID- 8751069
TI  - The role of anticipatory postural adjustments and gravity in gait initiation.
AB  - This study analyzes the anticipatory postural adjustments which precede heel-off
      by considering the participation of the gravitational and muscular actions about
      the ankle joints during the gait initiation process. The resultant moment about
      the ankle joints and the gravitational moment were calculated using a
      biomechanical model in five normal subjects for three different speed conditions.
      The results show that the variations of these two moments are correlated to the
      velocity at the end of the first step. Nevertheless, a significant variation of
      the ankle joints moment occurs at the beginning of the anticipatory phase,
      whereas the gravity effect is still insignificant. These findings show how the
      successive controls of the muscular actions acting during the anticipatory
      movement and of the gravity action acting principally during the step execution
      allow the subject to reach the velocity which has been initially and centrally
      decided, by the end of the first step.

PMID- 8751070
TI  - Stability properties of human reaching movements.
AB  - Through an experimental study of the stability properties of the human
      neuromuscular system while it performs simple point-to-point arm movements, this
      paper evaluates the concepts of equilibrium and virtual trajectories as a means
      of executing movement of the arm. Human subjects grasped the instrumented handle
      of a two-link robot manipulandum and performed specified point-to-point planar
      arm trajectories. Computer-controlled brakes were used to subtly change the
      movements by constraining the trajectory along an arc of radius equal to the
      length of one link of the manipulandum. Target points were arranged to lie along
      the arc so that the subject could complete the movement even when constrained.
      These situations were tested: (1) unconstrained throughout the movement, (2)
      constrained through the entire movement, and (3) initially constrained and then
      released during movement. Experimental results showed that the constraint evoked
      significant forces strongly oriented so as to restore the hand to the
      unconstrained hand path. In addition, when released from the constraint, these
      forces caused a strong tendency to return the hand to the unconstrained path
      before the end of the movement was reached. Such strong positional stability
      properties of the arm reinforce the notion that a moving attractor point
      dominates the dynamics of the arm during movement. Additionally, bounds on the
      shape of the virtual trajectory were found which indicate that the equilibrium
      point remains close to the actual movement produced. These results, showing that
      a controlled equilibrium point may be used for planning and coordinating
      multijoint movements, are consistent with an equilibrium point hypothesis.

PMID- 8751071
TI  - Phasic motor activity reduction occurring with horizontal rapid eye movements
      during active sleep in human.
AB  - We describe the phasic reduction of motor activity occurring with horizontal
      rapid eye movements (REMs) during active sleep in 15 children (12 healthy
      children and 3 patients with severe brain damage). A REM-related decrease in
      intercostal muscle activity was demonstrated by averaging integrated surface
      electromyograms. In the healthy subjects, this reduction had a mean latency from
      the REM onset of 37.1 ms and a duration of 225.9 ms. This phenomenon was also
      observed in the 3 patients who had lost cerebral function. We hypothesized a
      brainstem origin for the effect. A REM-related mentalis muscle activity loss,
      detected by averaging mentalis muscle twitches, was observed in 10 healthy
      children among the subjects. This loss began at 59.1 ms before the onset of REMs
      and lasted for 230.2 ms on average. In addition, a transient decrease in
      integrated REM activity surrounding mentalis muscle twitches (a twitch-related
      reduction of REMs) was observed. We discuss the similarity between REM-related
      phasic reduction of muscle activity obtained for intercostal and mentalis muscles
      and pontogeniculo-occipital (PGO) wave-related inhibitory postsynaptic potentials
      reported for feline lumbar and trigeminal motoneurons, respectively. We then
      assume the presence of a phasic event generator, functioning during active sleep
      in healthy humans, which triggers at least three generators; that is, the
      generator of PGO waves (or REMs), motor inhibition, and of motor excitation
      including muscle twitches.

PMID- 8751072
TI  - The effects of spaceflight on open-loop and closed-loop postural control
      mechanisms: human neurovestibular studies on SLS-2.
AB  - Stabilogram-diffusion analysis was used to examine how prolonged periods in
      microgravity affect the open-loop and closed-loop postural control mechanisms. It
      was hypothesized that following spaceflight: (1) the effective stochastic
      activity of the open-loop postural control schemes in astronauts is increased;
      (2) the effective stochastic activity and uncorrelated behavior, respectively, of
      the closed-loop postural control mechanisms in astronauts are increased; and (3)
      astronauts utilized open-loop postural controls schemes for shorter time
      intervals and smaller displacements. Four crew members and two alternates from
      the 14-day Spacelab Life Sciences 2 Mission were included in the study. Each
      subject was tested under eyes-open, quiet-standing conditions on multiple
      preflight and postflight days. The subjects' center-of-pressure trajectories were
      measured with a force platform and analyzed according to stabilogram-diffusion
      analysis. It was found that the effective stochastic activity of the open-loop
      postural control schemes in three of the four crew members was increased
      following spaceflight. This result is interpreted as an indication that there may
      be in-flight adaptations to higher-level descending postural control pathways,
      e.g., a postflight increase in the tonic activation of postural muscles. This
      change may also be the consequence of a compensatory (e.g., "stiffening")
      postural control strategy that is adopted by astronauts to account for general
      feeling of postflight unsteadiness. The crew members, as a group, did not exhibit
      any consistent preflight/postflight differences in the steady-state behavior of
      their closed-loop postural control mechanisms or in the functional interaction of
      their open-loop and closed-loop postural control mechanisms. These results are
      interpreted as indications that although there may be in-flight adaptations to
      the vestibular system and/or proprioceptive system, input from the visual system
      can compensate for such changes during undisturbed stance.

PMID- 8751074
TI  - Differential calcium signalling by m2 and m3 muscarinic acetylcholine receptors
      in a single cell type.
AB  - We have compared muscarinic acetylcholine receptor (mAChR) coupling to
      phospholipase C (PLC) and increases in cytoplasmic Ca2+ concentration [Ca2+]i in
      human embryonic kidney (HEK) cells, stably expressing either the human m3 or m2
      receptor subtype. In m3 mAChR-expressing cells, carbachol stimulated inositol
      phosphate (InsP) formation and increased [Ca2+]i with EC50 values of about 2
      microM and 30 nM, respectively. Maximal inositol 1,4,5-trisphosphate (InsP3)
      production (about fourfold) was rapid (15 s) and stable for 2 min. Maximal
      increases in [Ca2+]i were 300-350 nM and mainly, almost 90%, due to influx of
      extracellular Ca2+. The efficacy of pilocarpine for stimulating InsP and Ca2+
      responses was not significantly different from that of carbachol. All m3 mAChR
      mediated responses were pertussis toxin (PTX)-insensitive. In m2 mAChR-expressing
      cells, carbachol stimulated InsP formation and increased [Ca2+]i with EC50 values
      of about 20 microM and 7 microM, respectively. Maximal InsP formation was only 10
      15% of that observed in m3 mAChR-expressing cells, whereas maximal elevations of
      [Ca2+]i were similar in both cell types. Formation of InsP3 was rapid (15 s to 2
      min) and about twofold above basal. In contrast to m3 mAChR activation, [Ca2+]i
      increases induced by m2 mAChR activation were exclusively due to Ca2+
      mobilization from intracellular stores. The efficacy of pilocarpine for
      stimulating InsP and Ca2+ responses was 50% and 20% of the efficacy of carbachol,
      respectively. PTX treatment did not affect m2 mAChR-induced PLC stimulation, but
      reduced the m2 mAChR-mediated increases in [Ca2+]i to 50%. In conclusion, m3 and
      m2 mAChRs stably expressed in HEK cells can induce similar cellular responses;
      however, they do so by activating apparently distinct signalling pathways. While
      coupling of m2 mAChR to PLC occurs in a PTX-insensitive manner, coupling to
      mobilization of Ca2+ from intracellular stores is partly PTX-sensitive and this
      may occur at least partly independent of PLC activation.

PMID- 8751073
TI  - Regional differences in the density and subtype specificity of endothelin
      receptors in rabbit urinary tract.
AB  - We investigated the binding characteristics of endothelin (ET) receptors in
      rabbit ureter, bladder dome, bladder base, and urethra and compared the observed
      receptor properties with those of cloned human ETA and ETB receptors expressed in
      Chinese hamster ovary K-1 (CHO) cells. Receptor binding experiments with [125I]ET
      1 revealed the presence of a single class of specific, saturable, high affinity
      [125I]ET-1 binding sites in all of the regions of the studied urinary tract. The
      rank order of the densities (Bmax values) of [125I]ET-1 binding sites was: ureter
      "bladder dome > bladder base = urethra. ET-1 and ET-2 inhibited [125I]ET-1
      binding to the membrane particulates from the various regions of the urinary
      tract with single high affinity constants. A selective ETA receptor antagonist,
      BQ 123, and selective ETB agonists, ET-3 and sarafotoxin S6c (STXc), inhibited
      [125I]ET-1 binding to bladder dome, bladder base, and urethra with high and low
      affinity constants indicating the presence of both ETA and ETB receptor subtypes
      in these tissues. The subtype specificity of ET receptors in the rabbit tissues
      is confirmed with inhibition data obtained from similar binding studies in cloned
      human ETA and ETB receptors. The proportions of high affinity binding sites for
      ET-3, representing ETB receptors, were approximately 25%, 27%, and 46% in bladder
      dome, bladder base, and urethra, respectively. Corresponding values for STXc were
      approximately 17%, 28%, and 43% in bladder dome, bladder base, and urethra,
      respectively. In contrast to the findings for ET-3 and STXc, the proportions of
      high affinity binding sites for BQ 123, representing ETA receptors, in bladder
      dome, bladder base, and urethra were approximately 84%, 74%, and 60%,
      respectively. In ureter, these selective compounds inhibited [125I]ET-1 binding
      with either a low (ET-3 and STXc) or a high binding affinity (BQ 123), suggesting
      the presence of only a single receptor subtype (ETA) in this tissue. These data
      indicate that there are regional differences in the density and subtype
      specificity of ET receptors in the rabbit urinary tract.

PMID- 8751075
TI  - Reactive red 2: a P2y-selective purinoceptor antagonist and an inhibitor of ecto
      nucleotidase.
AB  - Effects of reactive red 2 and its parent compound acid red 33 were studied in rat
      vas deferens and guinea-pig taenia coli. In rat vas deferens, reactive red 2(1 to
      10 microM) shifted the concentration-response curve for the P2X-purinoceptor
      mediated contraction effect of alpha, beta-methylene ATP slightly to the right
      and progressively decreased the maximum (apparent antagonist Kd value 0.42
      microM). Acid red 33 (1000 microM) shifted the curve to the right without
      changing the maximum (apparent Kd 386 microM). The concentration-contraction
      curve of noradrenaline was not altered by reactive red 2. In the carbachol
      precontracted guinea-pig taenia coli, reactive red 2 (0.1 to 10 microM) shifted
      the concentration-response curve for the P2Y-purinoceptor-mediated relaxation
      effect of adenosine 5'-O-(2-thiodiphosphate) (ADP beta S) progressively to the
      right; only at the highest concentration of antagonist (10 microM) was the
      maximum slightly depressed; a pA2 value of 7.55 (Kd 0.028 microM) was derived
      from the shift. Acid red 33 (1000 microM) shifted the concentration-relaxation
      curve of ADP beta S to the right without changing the maximum (apparent Kd 171
      microM). Reactive red 2 (1 to 10 microM) also shifted the concentration-response
      curve for the relaxation effect of alpha, beta-methylene ATP, which is mediated
      by an unclassified P2-purinoceptor, progressively to the right but simultaneously
      decreased the maximum (apparent Kd 1.6 microM). The concentration-relaxation
      curve of 2-chloroadenosine was not altered by reactive red 2. Pieces of vas
      deferens and taenia coli degraded 76 and 66% of added ATP (10 microM) within 30
      min, respectively. Reactive red 2(0.1 to 100 microM) progressively reduced this
      degradation by up to 95%, with IC50 values of 3.9 +/- 0.6 and 3.9 +/- 2.3 microM,
      respectively. Acid red 33 (1000 microM) reduced the degradation by 30 and 20%,
      respectively. The results indicate that reactive red 2 is a relatively potent
      antagonist at both P2X-purinoceptors in rat vas deferens and P2Y-purinoceptors in
      guinea-pig taenia coli, with a 15 fold selectively for the P2Y-purinoceptor. It
      inhibits ecto-nucleotidase in both tissues. The dichloro-triazine residue that
      distinguishes the compound from acid red 33 greatly enhances the potency at both
      receptor subtypes as well as at the nucleotidase. As regards P2-purinoceptor
      subtypes, the results confirm the existence of two relaxation-mediating P2
      purinoceptors in guinea-pig taenia coli.

PMID- 8751076
TI  - Subtype determination of presynaptic alpha 2-autoreceptors in the rabbit
      pulmonary artery and human saphenous vein.
AB  - The pharmacological properties of the presynaptic a2-autoreceptors mediating
      inhibition of noradrenaline release were investigated in human saphenous vein and
      rabbit pulmonary artery. Segments of these blood vessels were incubated with
      [3H]noradrenaline and subsequently superfused with physiological salt solution
      containing uptake1 and uptake2 blockers. The potencies of a2-adrenoceptor
      antagonists in facilitating (pEC40) the electrically (2 Hz) evoked tritium
      overflow were determined. The order of potency and potency ratios of a2
      adrenoceptor antagonists obtained in our experiments were compared with the
      corresponding order of affinity and affinity ratios from radioligand binding
      studies in tissues and cells expressing only one of the alpha 2-adrenoceptor
      subtypes. In the rabbit pulmonary artery, oxymetazoline was a highly potent
      agonist at presynaptic a2-adrenoceptors, as reflected by its ability to inhibit
      at low concentrations the electrically evoked tritium overflow. However, in the
      human saphenous vein oxymetazoline behaved as a partial agonist, which, in
      interaction experiments with the a2-adrenoceptor agonist B-HT 920 (2-amino-6
      allyl-5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]-azepine), exhibited high potency in
      antagonizing the inhibitory effect of the latter drug on tritium overflow.
      Prazosin given alone at concentrations up to 1 mumol/l did not affect tritium
      overflow. The data obtained with oxymetazoline and prazosin make it very
      improbable that the a2-autoreceptors on the sympathetic nerves in both tissues
      are of the a2B- or a2C-subtype. In both blood vessels, rauwolscine given alone
      was highly potent in facilitating the electrically evoked overflow. In agreement
      with this, rauwolscine exhibited high potency in antagonizing the inhibitory
      effect of oxymetazoline on tritium overflow in the rabbit pulmonary artery and of
      B-HT 920 in the human saphenous vein. The ratio phentolamine/rauwolscine
      calculated from their potencies in increasing the electrically evoked tritium
      overflow was also used to discriminate between the various a2-adrenoceptor
      subtypes. Comparison of this potency ratio with the corresponding affinity ratios
      for a2-adrenergic binding sites on HT 29 cells, human platelets, bovine pineal
      gland, rat submaxillary gland, and cell lines transfected with the human a2 genes
      indicates that in the rabbit pulmonary artery and human saphenous vein the
      pharmacological characteristics of the autoreceptors conform best to those of a2A
      adrenoceptors. Finally, in both blood vessels the potencies of the antagonists
      BDF 6143 (4-chloro-2-(2-imidazolin-2-ylamino)-isoindoline), rauwolscine,
      corynanthine, phentolamine, idazoxan, SKF 104078 (6-chloro-9-[(3-methyl-2
      butenyl) oxyl]-3-methyl-1H-2,3,4,5-tetrahydro-3-benzazepine), and/or tolazoline
      in facilitating evoked noradrenaline release was determined. The potencies of
      these drugs which can discriminate between a2A- and a2D-adrenoceptors (but not
      between these and a2B/2C-adrenoceptors) were correlated significantly with their
      affinities for a2A, but not a2D, sites in radioligand binding studies. In
      conclusion, the present results suggest that the sympathetic nerves of the human
      saphenous vein and rabbit pulmonary artery are endowed with a2-autoreceptors of
      the a2A subtype.

PMID- 8751077
TI  - Nonexocytotic noradrenaline release and ventricular fibrillation in ischemic rat
      hearts.
AB  - In myocardial ischemia, nonexocytotic noradrenaline release has been identified
      as underlying mechanism of ischemia-evoked noradrenaline release. Nonexocytotic
      noradrenaline release can be suppressed by inhibitors of the neuronal
      noradrenaline carrier (uptake), such as desipramine. Utilizing this
      pharmacological intervention the role of local noradrenaline release in the
      genesis of ischemia-induced ventricular arrhythmias was studied. Regional
      ischemia was induced in rat isolated perfused hearts by ligature of the left
      anterior descending coronary artery, and the venous effluent obtained during the
      first 2 min of reperfusion was used to measure the release of endogenous
      noradrenaline by high-performance liquid chromatography methods. Coronary
      occlusion caused ventricular fibrillation in a well reproducible manner with an
      incidence of 70 to 80% during a 30 min observation period. Blockage of uptake1 by
      desipramine decreased the occurrence of ischemia-induced ventricular fibrillation
      to 60% (0.01 mumol/l) or 20% (0.1 mumol/l), and ventricular fibrillation was
      completely suppressed by 1 mumol/l desipramine. Likewise, desipramine (0.01-1
      mumol/l) concentration-dependently reduced endogenous noradrenaline release
      during 30 min of regional myocardial ischemia. Nisoxetine, a structurally
      unrelated inhibitor of uptake1, also suppressed ischemia-evoked ventricular
      fibrillation. In contrast to its antifibrillatory effect during regional
      myocardial ischemia, desipramine precipitated arrhythmias when ventricular
      fibrillation was induced by perfusing normoxic hearts with exogenous
      noradrenaline. Combination of desipramine (0.1 mumol/l) with exogenous
      noradrenaline (0.01 to 1 mumol/l) increased the incidence of ventricular
      fibrillation compared to noradrenaline perfusion alone. Under these conditions,
      uptake1-blockade is known to increase the extracellular concentration of the
      perfused noradrenaline. Finally, in the isolated, spontaneously beating papillary
      muscle of the left rat heart, desipramine (0.1 and 1.0 mumol/l) had no effect on
      the upstroke velocity of action potentials, the action potential duration and the
      effective refractory period. In conclusion, the findings demonstrate that
      nonexocytotic noradrenaline release is an important mediator of ischemia-induced
      ventricular fibrillation in isolated hearts of the rat. It is also documented
      that uptake1 inhibitors such as desipramine reveal their effects on ventricular
      fibrillation secondary to their action on transmembrane noradrenaline transport.

PMID- 8751078
TI  - Caffeine enhances sympathetic purinergic and noradrenergic transmission in the
      guinea-pig isolated vas deferens.
AB  - Intracellular recording techniques were used to monitor the resting membrane
      potential of smooth muscle cells and the excitatory junction potentials (EJPs)
      evoked by stimulation of the hypogastric nerve. Stimulation with trains of 15
      pulses at 1 Hz or 0.33 Hz evoked individual EJPs which increased in amplitude
      from the first pulse and reached a plateau after 6-8 pulses. Stimulation at 1 Hz
      resulted in EJPs facilitating to a plateau level of approximately 25 mV, whereas
      with stimulation at 0.33 Hz the EJPs only facilitated to a plateau level of about
      12 mV. With stimulation at 1 Hz, caffeine (3 mM and 10 mM), increased the
      amplitude of the first few EJPs in each train and decreased the extent of
      facilitation and reduced the amplitude of fully facilitated EJPs. In comparison,
      the amplitude of all EJPs evoked by stimulation at 0.33 Hz was increased by
      caffeine (3 mM and 10 mM). With 0.33 Hz stimulation, facilitation of the first
      few EJPs was observed in the presence of 3 mM caffeine but not in the presence of
      10 mM caffeine. In the presence of the alpha 2-adrenoceptor antagonist idazoxan,
      caffeine (3 mM and 10 mM) still enhanced the amplitude of EJPs early in trains of
      stimulation but there was no depression of EJPs later in the trains. Similarly,
      in reserpine-treated vasa deferentia, caffeine (3 mM) enhanced EJPs early in the
      train of stimulation at 1 Hz and there was no depression of EJPs at the end of
      the train. In addition to electrophysiological experiments, the effect of
      caffeine (0.1-30 mM) on the resting and stimulation-induced (S-I) efflux of
      radioactivity was investigated in guinea-pig isolated vasa deferentia previously
      incubated with [3H]-noradrenaline. Caffeine (10 mM) did not affect the resting
      efflux of [3H]-noradrenaline but significantly enhanced the S-I efflux by 150
      160%. The present findings suggest that caffeine enhances sympathetic purinergic
      and noradrenergic transmission at the sympathetic neuroeffector junction in the
      guinea-pig vas deferens. Moreover, the increased release of transmitter
      noradrenaline can modulate purinergic transmission by activation of alpha 2
      adrenoceptors located at sympathetic neuroeffector sites.

PMID- 8751079
TI  - Stimulation-induced 3H-L-citrulline accumulation in isolated longitudinal muscle
      myenteric plexus preparations of rat small intestine: a measure to characterize
      nitrergic neurons.
AB  - Nitric oxide (NO) synthase activity in rat isolated longitudinal muscle myenteric
      plexus preparations of the small intestine was determine by measuring the
      accumulation of 3H-L-citrulline during 30 min incubation with 3H-L-arginine. In
      untreated preparations a significant amount of 3H-L-citrulline accumulated in the
      tissue, about 2000 dpm/30 mg per 30 min, accounting for about 1.7% of the tissue
      radioactivity. Intermittent electrical field stimulation (15 Hz, 10 s trains with
      10 s intervals for total of 20 min) caused a threefold increase in 3H-L
      citrulline accumulation. The NO synthase inhibitor N omega-nitro-L-arginine
      methyl ester (L-NAME) reduced the spontaneous accumulation of 3H-L-citrulline by
      65% and prevented the electrically evoked increase. Removal of extracellular
      calcium or addition of tetrodotoxin blocked the electrically evoked increase in
      3H-L-citrulline accumulation without affecting spontaneous accumulation.
      Application of the calcium ionophore A 23187 (10 mumol/l) or 45 mmol/l) or 45
      mmol/l potassium caused a twofold increase in the accumulation of 3H-L
      citrulline. The muscarine receptor agonist oxotremorine (1 mumol/l) had no effect
      on spontaneous accumulation of 3H-L-citrulline, but inhibited the electrically
      evoked increase by about 50%, and this effect was blocked by scopolamine. A
      substantial amount of 3H-L-citrulline (15000 dpm) accumulated also in the
      incubation media, and this was increased 1.7-fold by the presence of A 23187 and
      2.7-fold by electrical stimulation. However, electrically evoked increase in 3H-L
      citrulline was not prevented by tetrodotoxin, in contrast to observation on
      tissue levels. In conclusion, during incubation with 3H-L-arginine tissue levels
      of 3H-L-citrulline in rat isolated longitudinal muscle myenteric plexus
      preparations, but not accumulation in incubation media may be used as a
      biochemical marker of the activity of nitrergic intestinal neurons which appear
      to be inhibited via muscarine receptors.

PMID- 8751081
TI  - Electrophysiological effects of dridocainide on isolated canine, guinea-pig and
      human cardiac tissues.
AB  - The cellular electrophysiological effects of dridocainide (EGIS-3966), a novel
      class I antiarrhythmic agent, was studied using conventional microelectrode
      techniques in canine cardiac Purkinje fibres and papillary muscle preparations
      obtained from humans and guinea-pigs. In each preparation, dridocainide (0.6-2
      mumol/l) decreased the maximum velocity of action potential upstroke (Vmax) in a
      frequency-dependent manner, although marked differences were observed in its
      effects in Purkinje fibre and ventricular muscle preparations. In canine Purkinje
      fibres, action potential duration measured at 50% and 90% of repolarization was
      decreased, while action potential duration measured at 10% of repolarization was
      increased by dridocainide. In addition, the plateau of the action potential was
      depressed by the drug. These changes in action potential configuration were not
      observed in guinea pig or human papillary muscles. The offset kinetics of the
      dridocainide-induced Vmax block were different in Purkinje fibres and in
      ventricular muscle: the slow time constant of recovery of Vmax was estimated to
      be 2.5 s in dog Purkinje fibre and 5-6 s in human and guinea-pig papillary
      muscle. In guinea-pig papillary muscle, the rate of onset of the Vmax block was
      0.15 and 0.2 per action potential in the presence of 0.6 and 2 mumol/l
      dridocainide, respectively. Dridocainide also decreased the force of contraction
      in this preparation. On the basis of the present results, dridocainide appears to
      possess mixed class I.C and I.A properties, with I.C predominance in human and
      guinea-pig ventricular muscle. Present results also indicate that results of
      conventional classification of class I drugs may depend on the parameters chosen,
      as well as on the preparation selected.

PMID- 8751080
TI  - Effect of SR 142801 on nitric oxide-dependent and independent responses to
      tachykinin NK3 receptor agonists in isolated guinea-pig colon.
AB  - We have determined the ability of the novel nonpeptide tachykinin (TK) NK3
      receptor antagonist, SR 142801, [(S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)
      piperidin-3-yl)propyl)-4-phenylpiperidin-4-yl)-N-methylaceta mide] in inhibiting
      the nitric oxide (NO)-independent prejunctional inhibition of cholinergic
      twitches and the NO-dependent relaxation produced by the NK3 receptor selective
      agonist, senktide, in the circular muscle of the guinea-pig proximal colon. Under
      moderate load (10 mN) and isometric recording of mechanical activity, single
      pulse electrical field stimulation (EFS) produced atropine- and tetrodotoxin
      sensitive twitch contractions of mucosa-free circular muscle strips from the
      guinea-pig proximal colon. In the presence of NK1 and NK2 receptor antagonists
      (SR 140333 0.01 microM and GR 94800 0.1 microM, respectively) the NK3 receptor
      selective agonist, senktide (EC50 33 pM) and the NK3 receptor preferring natural
      TK, neurokinin B (NKB, EC50 13 pM) produced a concentration-dependent slowly
      developing inhibition of cholinergic twitches. Senktide (1 nM) did not affect the
      contractile response to acetylcholine (1 microM) indicating that depression of
      evoked twitches occurs prejunctionally. The inhibitory effect of senktide was
      unaffected when evoked in the presence of the cyclooxygenase inhibitor (S)
      ketoprofen (10 microM), guanethidine (10 microM), naloxone (0.3 microM), the
      GABAB receptor antagonist 2-hydroxysaclofen (10 microM) or the combined
      application of the adenosine A1 and A2 receptor antagonists, 8-cyclopentyl-1,3
      dipropylxanthine (10 microM) and 3,7-dimethyl-1-propargylxanthine (30 microM)
      respectively. In the presence of NK1 and NK2 receptor antagonists, the NO
      synthase inhibitor L-nitroarginine (L-NOARG 30-100 microM) did not affect twitch
      inhibition induced by senktide (EC50 33 pM). The response to NKB (EC50 95 pM) was
      slightly reduced by L-NOARG, yet the bulk of the inhibitory effect of both
      agonists on cholinergic twitches was substantially independent of NO generation.
      SR 142801 (0.1-0.3 microM) produced a moderate rightward shift of the
      concentration-response curve to senktide without depression of the Emax to the
      agonist, yielding an apparent pKB value of 7.65. Under low resting tone (3 mN)
      and isotonic recording of mechanical activity, mucosa-free circular muscle strips
      from the guinea-pig proximal colon gained a high intrinsic tone suitable for
      testing the response to relaxant agents. In the presence of atropine (1 microM),
      guanethidine (3 microM), SR 140333 (0.01 microM) and GR 94800 (0.1 microM),
      senktide (EC50 50 pM) produced a concentration-dependent relaxation of the
      strips, which was blocked by L-NOARG. SR 142801 (0.01-0.1 microM) produced a
      large rightward shift of the L-NOARG-sensitive concentration-response curve to
      senktide yielding an apparent pKB value of 8.62. Under isometric recording
      condition, SR 142801 (0.1 microM) did not affect twitch inhibition produced by 3
      nM clonidine. Under isotonic recording condition, SR 142801 did not affect the L
      NOARG-sensitive relaxation produced by EFS. The present results indicate that NK3
      receptor stimulation produces a NO-dependent relaxation of the guinea-pig colon
      and a substantially NO-independent prejunctional inhibition of cholinergic
      twitches. The variable affinities of SR 142801 in antagonizing various senktide
      induced neuromodulatory effects in the guinea-pig intestine suggest a possible
      intraspecies heterogeneity of NK3 receptors in the enteric nervous system.

PMID- 8751082
TI  - CGRP inhibition of electromechanical coupling in the guinea-pig isolated renal
      pelvis.
AB  - We aimed at studying the mechanism(s) of the inhibitory effect exerted by
      calcitonin gene-related peptide (CGRP) on the spontaneous activity of the guinea
      pig isolated renal pelvis. In organ bath experiments, CGRP (1-100 nM) produced a
      concentration-dependent (EC50 8 nM) partial inhibition (Emax about 35% inhibition
      of motility index) of spontaneous contractions. The potassium (K) channel opener,
      cromakalim (3-10 microM) promptly suppressed the spontaneous contractions in a
      glibenclamide-(10 microM) sensitive manner. Glibenclamide (10 microM) did not
      affect the inhibitory action of CGRP. The calcium (Ca) channel agonist, Bay K
      8644 (1 microM), markedly enhanced the spontaneous activity of the renal pelvis
      and reduced the inhibitory effect of CGRP. The protein kinase A inhibitors Rp
      cAMPS (300 microM), H8 (100 microM) and H89 (10 microM), and the blockers of
      intracellular Ca handling by sarcoplasmic reticulum, ryanodine (100 microM) and
      thapsigargin (1 microM) did not affect the response to CGRP. The response to CGRP
      was likewise unaffected by the nitric oxide synthase inhibitor, L-nitroarginine
      (30 microM) and by the protein kinase G inhibitor, KT5823 (3 microM).
      Furthermore, the inhibitory action of CGRP was not modified by lowering the
      extracellular concentration of K (from 5.9 to 1.2 mM) nor by increasing (from 2.5
      to 3.75 mM) or decreasing (from 2.5 to 0.25 mM) the extracellular Ca
      concentration. Replacement of 80% glucose with 2-deoxyglucose (2-DOG) reduced the
      amplitude of spontaneous contractions, both in the absence and presence of 10
      microM glibenclamide. In the presence of 2-DOG, the inhibitory action of CGRP was
      enhanced at a similar extent, either in the absence or presence of glibenclamide.
      In sucrose gap, the effect of CGRP (0.1 microM for 5 min) was separately analyzed
      in the proximal (close to the kidney) and distal (close to the ureter) regions of
      the renal pelvis. Both preparations discharged spontaneous (pacemaker) action
      potentials having different shape, duration and frequently. CGRP had no effect on
      pacemaker potentials in the proximal renal pelvis while producing about 30%
      reduction of the frequency of pacemaker potentials and motility index in the
      distal renal pelvis. Cromakalim (3 microM) abolished pacemaker potentials in both
      regions of the renal pelvis. In conjunction with the results of previous studies
      in the guinea-pig ureter, the present findings document the existence of
      remarkable regional differences in the effector mechanisms initiated by CGRP
      receptor occupancy in the guinea-pig pyeloureteral tract. CGRP appears to be
      inherently unable to activate glibenclamide-sensitive K channels in the guinea
      pig renal pelvis, a mechanism which is central for its ability to suppress latent
      pacemakers in the ureter. Within the renal pelvis, the sensitivity to the
      inhibitory effect of CGRP appears in the more distal region, from which an
      'ureter-like' action potential is recorded.

PMID- 8751083
TI  - Electrophysiological analysis of the actions of pituitary adenylyl cyclase
      activating peptide in the taenia of the guinea-pig caecum.
AB  - The actions of pituitary adenylyl cyclase activating peptide (PACAP) on membrane
      potential and conductance were investigated in the taenia of the guinea-pig
      caecum. The possible role of PACAP in inhibitory transmission was also
      investigated. Membrane potentials of smooth muscle cells were measured by
      intracellular microelectrodes, in the presence of hyoscine and nifidepine (both
      10(-6)M. To determine conductance changes, current was passed from external plate
      electrodes using the technique of Abe and Tomita (1968). PACAP-27 caused a
      concentration dependent hyperpolarization of the muscle with a maximum of 12-15
      mV at 10(-6)M. The hyperpolarization caused by PACAP was associated with a
      substantial increase in membrane conductance. The hyperpolarization was abolished
      by apamin (10(-6)M), a blocker of small conductance, calcium-dependent, potassium
      channels, and was reduced to about 50% by suramin (10(-4)M), which is an
      antagonist of P2 receptors for purines. The hyperpolarization was not reduced by
      tetrodotoxin (2 x 10(-6)M), suggesting PACAP acts directly on the muscle. With
      continued exposure to PACAP, the hyperpolarization decayed back to resting
      membrane potential after several minutes, possibly due to receptor
      desensitization. Inhibitory junction potentials (IJPs) were markedly reduced in
      amplitude in the period of presumed receptor desensitization to PACAP, were
      abolished by tetrodotoxin, but were not affected by suramin. Apamin abolished the
      IJP and revealed a small excitatory junction potential. This study implies that
      PACAP released from nerve fibres in the taenia caeci hyperpolarizes the muscle
      via an opening of apamin-sensitive potassium channels. The action is probably
      through type I PACAP receptors.

PMID- 8751084
TI  - Large- and small-conductance Ca(2+)-activated K+ channels: their role in the
      nicotinic receptor-mediated catecholamine secretion in bovine adrenal medulla.
AB  - In cultured bovine adrenal chromaffin cells, charybdotoxin and iberiotoxin
      (inhibitors of the large-conductance Ca(2+)-activated K+ channel) as well as
      apamin (an inhibitor of the small-conductance Ca(2+)-activated K+ channel), at 1
      100 nM, suppressed carbachol-induced 86RB+ efflux, augmented carbachol-induced
      45Ca2+ influx via voltage-dependent Ca2+ channels and catecholamine secretion and
      had no effect on carbachol-induced 22Na+ influx via nicotinic receptors, a
      prerequisite for Ca2+ channel activation by carbachol. 45Ca2+ influx caused by
      high K+ (a direct activation of voltage-dependent Ca2+ channels) was also
      enhanced by these K+ channel inhibitors, with the concentration-response curves
      being similar to those for carbachol-induced 45Ca2+ influx. Dendrotoxin and mast
      cell degranulating peptide (inhibitors of voltage-dependent K+ channels), on the
      other hand, did not alter carbachol-induced 86Rb+ efflux or 45Ca2+ influx. These
      results suggest that the stimulation of nicotinic receptors eventually opens
      large- and small-conductance Ca(2+)-activated K+ channels, and that the blockade
      of these Ca(2+)-activated K+ channels results in gating of voltage-dependent Ca2+
      channels and thereby augments catecholamine secretion from bovine adrenal
      chromaffin cells.

PMID- 8751085
TI  - Evidence for a spinal origin of the effect of baclofen on the myocardial oxygen
      demand indexes.
AB  - In a previous study in anaesthetized rabbits we observed that electrical
      stimulation of the hypothalamic paraventricular nucleus (PVN) elicited
      substantial rises in the maximum rate of change of left ventricular pressure
      (dP/dtmax) and in myocardial oxygen demand indexes (rate-pressure product and
      triple product), similar to the changes observed during stress or physical
      effort. Baclofen, a selective GABA(B) receptor agonist, injected intravenously
      prevented these responses. In the present study, we show that low doses of
      baclofen (0.1, 0.3 and 1 microgram/kg), injected intrathecally (i.t.) at the T9
      level, reduced the myocardial oxygen demand during PVN stimulation. After 0.3
      microgram/kg baclofen i.t., the peak value of the triple product during
      stimulation was 140 +/- 20 compared with 193 +/- 20 before treatment. An i.t.
      injection (500 micrograms/kg), of saclofen a selective GABA(B) receptor
      antagonist, did not modify the resting haemodynamics significantly but attenuated
      the inhibitory effects of baclofen (3 mg/kg i.v.). These results suggest that the
      main site of the effects of baclofen is located within the spinal cord and that
      GABA(B) receptors probably mediate these effects by modulating the central
      control of cardiac function. In conclusion, baclofen might be a useful tool to
      prevent the centrally evoked increases of myocardial oxygen demand.

PMID- 8751086
TI  - Effects of the bradykinin antagonist, icatibant (Hoe 140), on pancreas and liver
      functions during and after caerulein-induced pancreatitis in rats.
AB  - It has been found earlier that the bradykinin antagonist, icatibant (Hoe 140),
      prevents the pancreatic oedema and the ensuing hypotension and
      haemoconcentration, and facilitates the removal of activated enzymes form the
      tissue during caerulein-induced acute pancreatitis. For a potential therapeutic
      use of the compound in clinical situations it is essential to investigate whether
      the associated increase in enzyme activities in the blood serum has any adverse
      effects on the pancreas itself or on other organs. Normal amylase secretion into
      the biliopancreatic duct stimulated by a low dose of caerulein (0.4 nmol kg-1 h
      1, i.v.) was not affect by icatibant (100 nmol kg-1, s.c.) Acute pancreatitis,
      induced by a high dose of caerulein (4 nmol kg-1 h-1 for 2 h, i.v.), resulted in
      elevations in the activities of amylase and lipase in the pancreatic tissue and
      in the blood serum lasting for at least 4 h after the end of the caerulein
      infusion. While the rise in enzyme activities in the blood serum was augmented in
      icatibant-treated rats only at the end of the caerulein-infusion, the enzyme
      accumulation in the pancreas was significantly reduced by icatibant for at least
      4 h after the end of the caerulein infusion. The secretion of amylase and lipase
      into the biliopancreatic duct was significantly increased only during the first
      20 min of acute pancreatitis; in rats pre-treated with icatibant, no significant
      increase could be observed. Twenty-four hours after induction of pancreatitis, a
      low-dose caerulein stimulation of the exocrine function of the pancreas led to a
      reduced but sustained secretion of amylase regardless of whether the animals had
      received icatibant or not. During the first 45 min of pancreatitis, blood glucose
      concentrations were significantly reduced, but returned to values not different
      from those obtained in saline-infused controls. This effect was not affected by
      icatibant. No changes in the response to an i.v. glucose tolerance test were
      found on the day after induction of acute pancreatitis. The serum activities of
      glutamic pyruvic transaminase and gamma-glutamyl transpeptidase determined up to
      24 h after induction of pancreatitis were not different from saline controls.
      icatibant had no effect on the activities of these enzymes. It is concluded that
      during caerulein-induced acute pancreatitis normal exocrine secretion of
      pancreatic enzymes into the pancreatic duct ceases almost immediately. Pre
      treatment with icatibant significantly reduces the accumulation of activated
      enzymes in the pancreatic tissue for several hours after induction of
      pancreatitis while a concomitant augmentation in enzyme activities in the blood
      serum lasts much shorter. There is no indication of adverse effects on the
      function of the endocrine or exocrine pancreas and that of the liver, either
      during the acute stages of pancreatitis or during the recovery period.

PMID- 8751087
TI  - Protein kinases in the locus coeruleus and periaqueductal gray matter are
      involved in the expression of opiate withdrawal.
AB  - The aim of this study was to evaluate the role played in the behavioral
      expression of morphine withdrawal syndrome by protein kinases in the locus
      coeruleus and the periaqueductal gray matter. Two different families of specific
      protein kinases have been investigated: serine/threonine and tyrosine kinases.
      Rats were implanted with cannulas into both the lateral ventricle and the locus
      coeruleus or the periaqueductal gray matter. Physical dependence was induced by
      chronic peripheral administration of morphine (from 7 to 30 mg/kg) and withdrawal
      syndrome was precipitated by injection of naloxone (2 micrograms) into the
      lateral ventricle. The administration of the serine/threonine kinase inhibitor 1
      (5-isoquinolinylsulfonyl)-2-methylpiperazine, H7 (1, 3, 10, and 30 nmol per side)
      into the locus coeruleus induced a strong attenuation of morphine withdrawal
      behavior. Signs related to the motor component of abstinence, such as jumping,
      rearing, and hyperactivity, were the most severely reduced. However, this effect
      was not dose-dependent, and the response was almost the same with all the doses
      used. A similar attenuation was observed after the injection of H7 (1, 3, and 10
      nmol per side) into the periaqueductal gray matter, but in this case motor signs
      were less strongly reduced and a larger number of signs were modified, mainly
      when using the highest dose. The administration of the tyrosine kinase inhibitor
      2-hydroxy-5-[N(2,5-dihydroxyphenyl)methyl]amino]-benzoic acid 3-phenylpropyl
      ester, KB23 (0.3, 1, and 3 nmol per side) into the locus coeruleus or the
      periaqueductal gray matter had no effect on the withdrawal syndrome behavior,
      except on teeth chattering. These results suggest that in the locus coeruleus and
      in the periaqueductal gray matter, serine/threonine kinases are implicated in the
      behavioral expression of morphine abstinence. In these brain structures, tyrosine
      kinases appear not to be involved.

PMID- 8751088
TI  - Inhibition of long-term potentiation in rat hippocampal slices by anandamide and
      WIN55212-2: reversal by SR141716 A, a selective antagonist of CB1 cannabinoid
      receptors.
AB  - It has been reported previously that delta 9-tetrahydrocannabinol and the
      synthetic cannabinoid agonist HU-210 [(--)-11-OH-delta 8-dimethylheptyl
      tetrahydrocannabinol] prevent long-term potentiation (LTP) induction in rat
      hippocampal slices. In this study we confirm that both WIN55212-2 ?R-(+)-(2,3
      dihydro-5-methyl-3-[?4-morpholinyl? methyl] pyrol [1,2,3-de]-1,4-benzoxazin-6-yl)
      (1-naphtalenyl) methanone monomethanesulphonate? (3 and 10 microM), another
      synthetic cannabinoid agonist, and anandamide (10 microM), considered to be the
      endogenous ligand of cannabinoid receptors, inhibit LTP formation in the Schaffer
      collateral-CA1 field complex. In addition, we show that SR141716A [N-(piperidin-1
      yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carboxamide
      hydrochloride] at 0.1-10 microM, a potent and selective antagonist of CB1
      cannabinoid receptors, concentration-dependently reversed the inhibition of LTP
      induced by both WIN55212-2 and anandamide. These data indicate that cannabinoid
      receptor agonists inhibit hippocampal LTP formation through CB1 receptor
      activation and that anandamide could be a candidate for an endogenous
      neuromessenger involved in memory processes.

PMID- 8751089
TI  - Functional serotonin 5-HT1D receptors and 5-HT1D beta receptor mRNA expression in
      human umbilical vein endothelial cells.
AB  - Pharmacological evidence has suggested the presence of 5-hydroxytryptamine (5-HT,
      serotonin), 5-HT(1D) receptors on endothelial cells but these receptors have
      never been identified unambiguously on this type of cells. We now report that
      human umbilical vein endothelial cells (HUVEC) express 5-HT(1D) receptors coupled
      to inhibition of cyclic AMP formation. 5-HT and 5-HT(1D) receptor agonists 5
      carboxamidotryptamine (5-CT) and sumatriptan were approximately equipotent at
      inhibiting forskolin-stimulated cyclic AMP accumulation in HUVEC (mean pEC50 7.6
      8.2, maximal effect 30% inhibition). The 5-HT(1A) receptor antagonist, 8-OH-DPAT
      was clearly less potent (pEC50 6.2) and less efficacious. The selective 5-HT(1D)
      receptor agonist, GR127935 (1 nM) markedly inhibited the effect of 5-HT (apparent
      pK(B) 10.8). Reverse transcription-polymerase chain reaction analysis showed the
      mRNA for 5-HT(1D beta) receptors to be expressed in HUVEC. These results
      demonstrate the presence of functional 5-HT(1D) receptors and the expression of 5
      HT(1D beta) receptor mRNA in HUVEC. They support the involvement of 5-HT(1D beta)
      receptors in endothelial-mediated responses to 5-HT.

PMID- 8751090
TI  - RU 24969-induced locomotion in rats is mediated by 5-HT1A receptors.
AB  - The locomotor response to RU 24969 (5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)
      1H-indole; 10 mg/kg, s.c.), a preferential 5-HT(1B) receptor agonist, was
      investigated in the rat, using two novel 5-HT(1A) receptor antagonists, WAY
      100635 (0.3 mg/kg and 1 mg/kg, s.c.) and SDZ 216-525 (0.3 mg/kg, s.c.), and the
      novel 5-HT(1B)/5-HT(1D) receptor antagonist, GR 127935 (1 mg/kg, s.c.). The
      antagonists per se did not alter spontaneous locomotion. Both selective 5-HT(1A)
      receptor antagonists blocked RU 24969-induced hyperlocomotion, whilst the 5
      HT(1B) receptor antagonist was without effect. These results suggest that RU
      24969-induced hyperlocomotion in the rat is mediated by 5-HT(1A) receptors.

PMID- 8751091
TI  - Probes and polymerase chain reaction for detection of food-borne bacterial
      pathogens.
AB  - DNA-hybridization and the polymerase chain reaction (PCR) are techniques commonly
      used to detect pathogenic bacteria. In this paper, the use of these techniques
      for detection of Salmonella, E. coli, V. cholerae, non-O1 Vibrio, Yersinia
      enterocolitica, Campylobacter, Listeria monocytogenes, Staphylococcus aureus,
      Bacillus cereus, Clostridium perfringens, and C. botulinum is reviewed with
      emphasis on application in food microbiology. In food control, DNA-techniques
      have most often been used in a 'culture confirmation' fashion, i.e. bacteria are
      enriched and sometimes even purified by traditional culture procedures and
      thereafter identified by the use of DNA-based methods. The most desirable
      approach is, however, to detect organisms directly in the food, but major
      problems remain to be solved before this can be routinely performed.

PMID- 8751092
TI  - Yeasts associated with Cheddar and Gouda making.
AB  - Sources of yeast contamination which may lead to contamination of the curd during
      Cheddar and Gouda cheese making, were examined in a single cheese factory. A
      total of 187 representative yeast isolates present in the factory environment, on
      working surfaces, the brine and on workers' hands and aprons were identified
      according to conventional methods and cellular long-chain fatty acid analyses.
      Product line samples were taken at critical control points in the manufacturing
      process and analysed after incubation at 25 degrees C for 96 h. The most
      prevalent isolates belonged to the genera Debaryomyces and Candida. Other genera
      encountered were Cryptococcus, Rhodotorula, Yarrowia, Pichia, Trichosporon,
      Torulaspora, Issatchenkia, Saccharomyces and Zygosaccharomyces. Characterization
      of the predominant yeast isolates indicated that the cheese brine was responsible
      for the largest variety and number of yeast isolates yielding a total of 64 yeast
      strains belonging to nine different genera.

PMID- 8751093
TI  - Taxonomy of lactic acid bacteria associated with vacuum-packaged processed meat
      spoilage by multivariate analysis of cellular fatty acids.
AB  - The taxonomy of lactic acid bacteria from vacuum-packaged processed meats is
      problematic, and atypical members of the leuconostocs and the Lactobacillus sake
      / curvatus group are often encountered. In order to resolve this problem the
      cellular fatty acid (CFA) content of 61 isolates from vacuum-packaged vienna
      sausages and 18 reference strains was determined by gas chromatography. The
      relationship between strains was derived by principal component analysis of data.
      The CFA profiles were highly reproducible. Although no relationships could be
      derived using only one or two differentiating CFAs, plots of the first two
      principal components based on only the six most variable CFAs allowed grouping of
      strains. The two genera (Leuconostoc and Lactobacillus) could not be clearly
      separated when analysed together, but differentiation of species within each of
      the genera was achieved when they were analysed independently. Examination of
      plots for the reference strains confirmed previously established relationships
      between these strains. From the plot of the Lactobacillus sake / Lactobacillus
      curvatus component of the study it was found that most atypical Lactobacillus
      sake / curvatus strains were closely related to the typical Lactobacillus sake
      isolates and reference strain, while the Lactobacillus curvatus strains formed an
      independent grouping. A small cluster of atypical strains, however, indicated
      that this relationship may not be true for all these strains. Among the
      leuconostocs only isolates of Leuconostoc mesenteroides could be clearly
      differentiated.

PMID- 8751094
TI  - Prevalence of vibrio cholerae and salmonella in a major shrimp production area in
      Thailand.
AB  - In 1992 and 1993, a 7 months study carried out in a major shrimp-producing area
      in Southern Thailand to study the prevalence of Vibrio cholerae and Salmonella. A
      total of 158 samples were examined including water, sediment, shrimp, pelleted
      feed, shrimp gut, and chicken manure. Salmonella was not recovered from any
      sample type studied. V. cholerae O1 was isolated from 2 (2%) and V. cholerae non
      O1 was isolated from 35 (33%) of 107 samples examined. The occurrence of V.
      cholerae was not significantly influenced by water salinity, temperature,
      dissolved oxygen or pH. There was no correlation between fecal coliform counts
      and the prevalence of V. cholerae. The results indicate that V. cholerae non-O1
      is ubiquitous in aquatic environments where shrimp culture is practised under a
      variety of environmental conditions. The public health significance of non-O1 V.
      cholerae in shrimp culture remains to be determined. V. cholerae O1 and
      Salmonella do not appear to constitute a hygienic problem even if chicken manure
      was used as fertilizer.

PMID- 8751095
TI  - Tissue plasminogen activator as a biochemical adjuvant in vitrectomy for
      proliferative diabetic vitreoretinopathy.
AB  - Tissue plasminogen activator (TPA) converts plasminogen to plasmin, thereby
      inducing fibrinolysis. In ophthalmologic surgery of subretinal hemorrhages, it is
      used to dissolve blood clots. As the blood-retina barrier of diabetic patients
      has broken down, plasminogen can enter the vitreous compartment in these cases.
      It is known that plasmin dissolves extracellular matrix protein in the vitreous
      interface. For that reason se used TPA in pars plana vitrectomy (ppV) of
      proliferative diabetic vitreous retinopathy (PDVR). Ten patients undergoing ppV
      for PDVR of stage A or B (Kroll classification) were included in a prospective
      study. At 15 min prior to vitrectomy, 100 microliters balanced salt solution was
      injected into the vitreous cavity. As randomized, the injection fluid contained
      either 25 micrograms TPA or only buffer solution. At this stage, the operating
      surgeon did not know whether TPA was injected or not. The grade of difficulty and
      complications of the operation were scored and documented. In all cases the
      operating surgeon correctly classified verum or placebo after surgery.
      Preparation of vitreous cortex and pathological membranes proved to be less
      difficult when TPA had been injected. Moreover, no severe bleeding occurred in
      this group in spite of marked PDVR. We conclude that TPA can be used in ppV
      without producing severe side effects. Disintegration of the vitreous interface
      causes a posterior detachment of the vitreous body, thus facilitating ppV.

PMID- 8751096
TI  - Severe occlusive retinal periphlebitis with vitreous hemorrhage in multiple
      sclerosis.
AB  - Severe ocular complications in multiple sclerosis are rare. A 43-year-old patient
      had a history of diplopia episodes and optic neuritis in the right eye between
      1979 and 1980. In 1984, multiple sclerosis had been diagnosed. The patient
      presented with visual deterioration in the right eye in 1992. Ophthalmoscopy and
      fluorescein angiography showed severe occlusive retinal periphlebitis with
      diffuse retinal hemorrhages and large areas of nonperfusion. At the time of
      presentation the patient was in general good health and presented no neurological
      sign. Examinations for other causes of periphlebitis were negative. Although
      treatment with laser therapy and corticosteroids was initiated, the patient
      developed recurrent vitreous hemorrhages that required pars plana vitrectomy. In
      1993 the patient suffered from a general deterioration of the disease course and
      was treated with systemic immunosuppressive medication. Vitreous hemorrhage is a
      rare complication of multiple sclerosis.

PMID- 8751097
TI  - Protein C, protein S, and antithrombin III in acute ocular occlusive diseases.
AB  - Hereditary and acquired deficiencies of protein C, protein S, and antithrombin
      III are important risk factors of thrombosis, especially in peripheral veins. In
      a prospective study, concentrations of these factors were measured to determine
      the prevalence of deficiencies of these proteins in ocular vascular occlusive
      disease. A total of 167 patients with acute retinal arterial (28%) or venous
      occlusion (55%) or ischemic optic neuropathy (17%) were included. Exclusion
      criteria were anticoagulant therapy, renal insufficiency, and hepatic disease.
      The mean values obtained for all patients were in normal range (protein C, 102 +/
      25%; protein S, 109 +/- 22%; antithrombin III, 23.6 +/- 3.1 IU/ml). Antithrombin
      III was pathologically reduced in one patient with branch venous occlusion.
      Proteins C and S were severely altered in two patients with central venous
      occlusion, in one individual with ischemic optic neuropathy, and in one patient
      with branch arterial occlusion. Subnormal values were found in 21 patients for
      antithrombin III (16.1-19.9 IU/ml), in 7 patients for protein C (55-65%). Two of
      these five patients with pathologic findings showed severe vascular
      manifestations in the form of current deep-vein thrombosis and multiple retinal
      occlusions. Their age was 30 and 53 years, respectively, and differed
      considerably from the mean age of the entire group (65 +/- 12 years). This study
      suggests that these proteins were important factors for the development of ocular
      vascular occlusive diseases in single patients. Although the prevalence is low,
      measurement of these parameters in young patients may be useful in preventing
      other vascular complications.

PMID- 8751098
TI  - Colour contrast sensitivity in patients with age-related Bruch's membrane
      changes.
AB  - Patients with bilateral drusen as a manifestation of early age-related macular
      degeneration (AMD) may have minor psychophysically detectable visual defects in
      the presence of normal visual acuity. In a variety of retinal diseases, one of
      the earliest changes in visual processing is an impairment of normal colour
      vision. This study was undertaken to evaluate colour vision deficits in patients
      with macular drusen and to determine whether changes in colour contrast
      sensitivity may occur over time. In a prospective study, colour vision in 84 eyes
      of 84 patients aged 55-84 years (mean, 68.89 +/- 6.23 years) with macular drusen
      and clear media was tested using a computer graphics technique. A total of 47
      patients were reviewed annually for up to 2 years and measurements were obtained
      at annual intervals. Colour contrasts sensitivity along protan, deutan and tritan
      colour confusion lines was determined at a foveal and a parafoveal region. The
      sensitivity to all stimuli showed large variations between patients. The
      thresholds for foveal blue-colour contrast sensitivity were elevated and
      increased during the review period. In contrast, there was no significant change
      in sensitivity with time for red and green at the foveal or parafoveal region.
      Tritan threshold changes suggest that the SW cone-receptor population is more
      susceptible to damage associated with early age-related macular disease than are
      red or green cones. The results indicate that blue colour contrast sensitivity
      determined over time may serve as a measure to assess the progression of age
      related maculopathy prior to the manifestation of atrophic or exudative macular
      lesions associated with visual loss.

PMID- 8751099
TI  - Clinical investigation of the combination of a scanning laser ophthalmoscope and
      laser Doppler flowmeter.
AB  - In this report we present the clinical applications of a new noninvasive method
      of imaging in high definition the topography of perfused retinal vessels. By the
      combination of a laser Doppler Flowmeter with a scanning laser system the retinal
      circulation can be visualized and quantified. The principles of measuring blood
      flow by laser Doppler flowmetry are based on the laser Doppler effect: laser
      light scattered by a moving particle is shifted in frequency. The scanning laser
      system is a modified laser scanning tomograph (technical data: retinal area of
      measurement, 2.7 x 0.7 mm; 10 degrees field with 256 points x 64 lines;
      horizontal digital resolution, 10 microns; wave-length, 670 nm; light power, 100
      micro W; data acquisition time, 2.048 s). Every line is scanned 128-times at a
      line-sampling rate of 4000 Hz. By the performance of discrete fast fourier
      transformation over 128 intensities of each retinal point the laser Doppler shift
      is calculated for each retinal point. With these data a 2-dimensional map of the
      retinal perfusion with 256 x 64-points is created. The brightness of the picture
      point is coded by the value of the Doppler shift. By this method we examined
      health eyes with normal intraocular pressure (IOP) and artificially increased IOP
      and eyes with glaucomatous optic nerve atrophy, proliferative diabetic
      retinopathy with areas of capillary occlusion, arterial hypertension with
      microinfarction of the retina, and central retinal artery occlusion. The
      application of "scanning laser Doppler flowmetry" (SLDF) leads to the
      visualization of perfused vessels and capillaries of the retina in high
      resolution. The examination of perfused retinal arterioles, veins, and
      capillaries by this method represents the anatomical situation. In SLDF the area
      of normal or impaired retinal circulation becomes visible (capillary
      nonperfusion, proliferative vascular structures), whereby the extent of the
      perfusion is proportional to the brightness of the imaged vessel; the brighter
      the vessels or capillaries, the higher the blood flow inside the vessels. Retinal
      areas with low capillary flow are "dark" and show no visible vessel. In imaging
      of an eye with central retinal artery occlusion, retinal arterioles, veins, or
      capillaries were invisible due to the lack of retinal perfusion. Only ciliary
      source vessels of the optic nerve head were bright and visible, indicating normal
      ciliary circulation. SLDF facilitates the visualization of perfused retinal
      capillaries and vessels in high resolution. The representation of the function of
      the retinal circulation by SLDF leads to an image similar to the anatomical
      situation. The two-dimensional mapping of local blood flow leads to a
      physiological picture of the retinal perfusion with visible vessels and
      capillaries.

PMID- 8751100
TI  - Extension of a recent therapy for dyslexia.
AB  - Recently, peculiarities of visual perception were found in dyslexic patients.
      Therefore, we investigated visual acuity, reading and spelling capabilities, as
      well as peripheral letter recognition in 54 children with reading and/or spelling
      problems. Subsequently, the children and their parents trained at home for
      approximately 0.5 h daily during 2-3 months. Training consisted of reading
      through a small aperture and of visuomotor coordination tasks. The mean results
      obtained in a reading test for all patients improved significantly after the
      training, but less so than those recorded in previous studies on children
      suffering from dyslexia. Although the therapy clearly improved performance, it
      was less specific than previously claimed.

PMID- 8751101
TI  - Eye movement in amyotrophic lateral sclerosis: a longitudinal study.
AB  - Eye muscles and the sphincter muscles of the bowel and bladder were formerly
      thought to be spared in amyotrophic lateral sclerosis (ALS), a neurodegenerative
      disorder. As frequent subclinical impairment of the anal sphincter muscles in ALS
      has recently been reported, We suspected an earlier and more frequent, if
      subclinical, involvement of the oculomotor system than hitherto described.
      Starting in 1993, we repeatedly studied oculomotor involvement in eight patients
      with (ALS) using routine orthoptic examination techniques as well as electro
      oculographic recordings of ocular movements. Three patients had consistently
      normal clinical examinations but progressive changes in electro-oculography
      (EOG). Three patients showed intermittent impairment of eye movements with normal
      EOG (one patient) or with progressive changes on EOG examination. In two
      patients, both clinical examination and EOG were progressively pathologic. These
      findings provide further evidence of early oculomotor involvement, e.g., prior to
      respiratory failure, in ALS than previously suspected. Since EOG changes seemed
      to be detectable in all but one patient, EOG changes may allow earlier,
      subclinical detection of impaired eye movement and thus reveal even an increased
      frequency of oculomotor impairment in ALS. Due to the heterogeneity of ALS the
      number of patients examined to settle finally the question of oculomotor
      involvement in ALS needs to be increased. Newly developed software will allow
      further interpretation and comparison of more data and, thus, should offer
      further help in detecting early changes.

PMID- 8751102
TI  - Long-term treatment of blepharospasm with botulinum toxin type A.
AB  - The treatment of essential blepharospasm with botulinum toxin has been known for
      a decade and is becoming increasingly more popular. To our knowledge, only a few
      longterm studies in major patient populations have been published. Of a total of
      more than 1,600 patients, results of treatment were evaluated in 115 patients (31
      men and 84 women) treated continuously for a minimum of 3 years and a maximum of
      8 years (mean, 5.7 years). Patients were divided into two groups. Group I
      represents the "good responders" and contains all patients who received only 4-10
      injections over that time (n = 55). Group II represents the "poor responders, "
      who received at least 20 injections over that period (n = 60). Group I received a
      mean of 7.1 injections, whereas group II had a mean of 24.4 injections (total,
      1,855). In group I the beneficial effect lasted for an average of 14.6 weeks
      (range, 2-52 weeks), whereas group II had a mean beneficial effect for only 6.8
      weeks (range, 0-18 weeks). The time of efficacy remained statistically stable
      even in the case of frequent treatment (up to 36 injections in group II).
      Systemic or severe long-lasting local side effects were never observed; the most
      frequent side effects were: group I-ptosis, 5.4%; tearing, 5.1%; double vision,
      1.8%; and lid lag, 1.5%; group II-ptosis, 4.3%; tearing, 3.3% lid lag, 1.9%, and
      double vision, 1.6%. The treatment of essential blepharospasm with botulinum
      toxin is a very effective therapy with minimal and transient complications. It
      may be used for long-term treatment without showing a decrease in efficacy.

PMID- 8751103
TI  - Tapered transition zone and surface smoothing ameliorate the results of excimer
      laser photorefractive keratectomy for myopia.
AB  - This report compares the results we obtained after photorefractive keratectomy
      (PRK) for myopia using different treatment modalities. PRK was performed on 35
      eyes (group 2; mean refraction, -5.7 +/- 2.3 D) using a tapered transition zone
      (TTZ), smoothing of the corneal surface, and somewhat more steroids than usual.
      The results were compared with those obtained in another group of patients (group
      1) with equally high myopia in whom these measures were not used. Quicker
      rehabilitation and stabilization of visual acuity (VA) and less regression were
      observed. An uncorrected VA of +/- 20/40 after 9 months was found in 94.4% of
      eyes in group 1 (P = 0.026). A refraction of +/- D after 9 months was found in
      89% of eyes in group 2 and in only 58% of eyes in group 1 (P = 0.024). Haze
      reduction was quicker and stronger in group 2, and fewer patients in this group
      suffered loss of best corrected VA. The results of PRK of myopia can be
      ameliorated thanks to improved technique and increased experience.

PMID- 8751104
TI  - Prophylactic Nd:YAG-laser iridotomy versus surgical iridectomy: a randomized,
      prospective study.
AB  - Both surgical iridectomy and YAG-laser iridotomy have been shown to prevent angle
      closure glaucoma. However, it remains unknown as to which procedure is superior.
      We therefore conducted a prospective randomized study, which compared the effect
      of the two methods on visual acuity, intraocular pressure, endothelial cell
      density, depth of the anterior chamber, and iris configuration as well as
      acceptance by the patients. A total of 30 patients, who were treated for acute
      angle-closure glaucoma in one eye, were subjected to either surgical iridectomy
      or Nd:YAG-laser iridotomy in the other eye according to a randomized protocol.
      All patients were followed for 12 months by examination at the 1st, 6th, and 12th
      month post treatment. No significant difference between the two treatments was
      found regarding visual acuity or intraocular pressure. The peripheral anterior
      chamber increased in depth following both methods, whereas the central depth of
      the anterior chamber was unaffected. A better gonioscopic visibility of the
      trabecular meshwork resulted from the increased width of the chamber angle.
      Whereas the number of endothelial cells remained constant in the patients treated
      with laser iridotomy, a small decrease was observed in the group of patients who
      underwent iridectomy (-7.2% after 12 months; difference not significant). The
      subjective acceptance by the patients was better in the group treated with laser
      iridotomy. We conclude that the two methods are equivalent with regard to
      intraocular pressure and visual acuity. The constant number of endothelial cells
      and the better acceptance by the patients suggest Nd:YAG-laser iridotomy to be
      the preferable method for prophylaxis of acute angle-closure glaucoma.

PMID- 8751105
TI  - Panophthalmitis with acute scleral necrosis after brachytherapy of a malignant
      melanoma of the ciliary body.
AB  - A 52-year-old man who presented with a large ciliochoroidal malignant melanoma
      was treated by application of a 106Ru plaque. At 8 days after removal of the
      plaque, severe panophthalmitis with rapidly progressive scleral necrosis at the
      site of the tumor made enucleation inevitable because of impending perforation of
      the globe. Microscopic examination revealed an intense inflammatory response and
      almost complete necrosis of the tumor and overlying sclera. Possible mechanisms
      for the occurrence of this rare complication are discussed.

PMID- 8751106
TI  - Immunohistological and ultrastructural study of the developing tendons of the
      avian foot.
AB  - The aim of the present report is to provide a detailed description of the
      morphogenesis and initial differentiation of the long tendons of the chick foot,
      the long autopodial tendons (LAT), from day 6 to day 11 of development. The fine
      structure of the developing LAT was studied by light and transmission electron
      microscopy. The characterization by immunofluorescent techniques of the
      extracellular matrix was performed using laser scanning confocal (tenascin,
      elastin, fibrillin, emilin, collagen type I, II, III, IV and VI) or routine
      fluorescence (tenascin, 13F4) microscopy. In addition, cell proliferation in
      pretendinous blastemas was analyzed by the detection of BrdU incorporation by
      immunofluorescence. The light microscopic analysis permitted the identification
      of different stages during LAT morphogenesis. The first stage is the formation of
      a thick ectoderm-mesenchyme interface along the digital rays, followed by the
      differentiation of the "mesenchyme lamina", an extracellular matrix tendon
      precursor, and ending with the formation and differentiation of the cellular
      condensation that forms the tendon blastema around this lamina. The
      immunofluorescence study revealed the presence and arrangement of the different
      molecules analyzed. Tenascin and collagen type VI are precocious markers of the
      developing tendons and remain present during the whole process of tendon
      formation. Collagen type I becomes mainly restricted to the developing tendons
      from day 7.5. Collagens type II and IV are never detected in the developing
      tendons, while a faint labeling for collagen type III is first detected at day 7.
      The analysis of the distribution of the elastic matrix components in the
      developing tendons is a major contribution of our study. Elastin was detected in
      the periphery of the tendons from day 8 and also in fibrils anchoring the tendons
      to the skeletal elements. At the same stage, emilin strongly stains the core of
      the tendon rods, while fibrillin is detected a little later. Our study indicates
      the existence of an ectoderm-mesoderm interaction at the first stage of the
      tendon formation. In addition, our results show the different spatial and
      temporal pattern of distribution of extracellular matrix molecules in developing
      tendons. Of special importance are the findings concerning the tendinous elastic
      matrix and its possible role in tendon maturation and stabilization.

PMID- 8751107
TI  - Histocytochemical and immunohistochemical studies related to the role of glycogen
      in human developing digestive organs.
AB  - To elucidate the role of glycogen in the epithelium of developing digestive
      organs, we investigated the appearance of glycogen and glycogen phosphorylase
      (GP) in these organs. We studied 64 externally normal human embryos at Carnegie
      stages 13-23 (5.1-28.0 mm in crown-rump length, 4-8 weeks of gestation) by
      histocytochemical staining for glycogen and immunohistochemical staining with
      antibodies against two isoenzymes of GP: brain-type (BGP) and muscle-brain-type
      (MBGP) GP. At stage 13, glycogen appeared in the epithelium of the digestive
      tract and the parenchyma of the pancreas. As development advanced, glycogen
      granules increased in number and size in these tissues, and they became evenly
      distributed in the epithelium of the digestive tract as either single particles
      or aggregates, as deduced by electron microscopy at late embryonic stages.
      Immunoreactivity specific both for BGP and for MBGP was detected in the digestive
      tract and the pancreas from stage 13. As development advanced, both BGP- and MBGP
      immunoreactive cells increased in number and in immunoreactivity, and the number
      of MBGP-immunoreactive cells became larger than that of BGP-immunoreactive cells.
      By contrast, in hepatic cells, which serve as a major storage site for glycogen
      in adults, glycogen was detected only from stage 20, in smaller amounts, without
      formation of aggregates, and no immunoreactivity specific for BGP or MBGP was
      apparent throughout the embryonic stages examined. Thus, in the epithelium of the
      digestive tract and the parenchyma of the pancreas, but not in hepatic cells, the
      appearance and localization of GP coincided almost exactly with that of glycogen.
      These observations suggest that glycogen in the epithelium of the digestive tract
      and the parenchyma of the pancreas has not only been synthesized but also
      degraded from an early embryonic period and may, thus, be related to active
      cellular metabolism that is specific for embryonic development, including
      proliferation of the epithelium and interactions between epithelium and
      mesenchyme.

PMID- 8751108
TI  - Distribution of alpha 2-adrenergic binding sites in the parabrachial complex of
      the rat.
AB  - The present study describes the distribution of alpha 2-adrenoceptors in the
      parabrachial and Kolliker-Fuse nucleus of the rat by employing the tritium
      labeled alpha 2-receptor antagonist rauwolscine ([3H]-RAUW) as a ligand. The [3H]
      RAUW binding was densitometrically quantified in five nuclei of the parabrachial
      (PB) complex in serial coronal sections. We found that cytoarchitectonically and
      anatomically distinct nuclei of the PB complex exhibit different numbers of [3H]
      RAUW-binding sites. The largest number of binding sites was observed over the
      external lateral PB and caudally over the waist area of the PB. Lower numbers of
      binding sites were found in the remaining lateral PB nuclei, followed by the
      medial PB and the Kolliker-Fuse nucleus. In addition we disclosed that the
      internal lateral PB contains a very low number of binding sites while the
      external medial PB is marked by dense [3H]-RAUW binding. Also, the affinities of
      the binding sites differed between the PB areas. High affinities were observed in
      the external lateral PB, the remaining lateral PB nuclei and in the waist area of
      the PB, while the medial PB and the Kolliker-Fuse nucleus exhibited only low
      affinities for the ligand. Furthermore, saturation curves demonstrated non-linear
      profiles, indicating the presence of more than one population of binding sites in
      the PB nuclei for the radioligand. Our data demonstrate that the PB exhibits a
      distinct distribution of alpha 2-adrenergic binding sites. These correlate well
      with the cytoarchitectonically defined nuclei of the PB complex and with the
      pattern of ascending axons from the medial nucleus of the solitary tract and the
      area postrema terminating in the PB. Since a large number of these projection
      neurons utilize adrenaline or noradrenaline as their transmitters, we conclude
      that solitary-parabrachial neurotransmission to the forebrain is, at least in
      part, mediated via alpha 2-adrenoceptors.

PMID- 8751109
TI  - Early development and organization of the retinopetal system in the larval sea
      lamprey, Petromyzon marinus L. An HRP study.
AB  - Development of the retinopetal system of the larval sea lamprey, Petromyzon
      marinus, was investigated following labelling of this system by injection of
      horseradish peroxidase into the orbit. This study extends our previous report on
      larval stages and provides a detailed description of the development of this
      system. We present quantitative and qualitative evidence suggesting that the
      retinopetal nuclei of Schober's M2-M5 nucleus, the mesencephalic reticular area
      and the tectum arise sequentially in that order, that the three retinopetal
      nuclei originate from a common anlage in the ventricular zone of the
      mesencephalic tegmentum and that the retinopetal cell population increases
      throughout the larval period. No neuronal death was observed. We also describe
      and discuss the significance of a transitory phase of retinopetal cell
      differentiation characterized by the presence of ventricular dendrites. Finally,
      we compare the development of retinopetal and retinofungal systems.

PMID- 8751110
TI  - Development of the retinal circulation in the pig.
AB  - Retinal angiogenesis was studied in 300 eyes of 150 porcine fetuses by means of
      semithin histologic sections and vascular corrosion casts. In the embryonic and
      early fetal period, the retina is avascular and nourished via diffusion from the
      choriocapillaris and the vascular tunic of the lens. The development of the inner
      vascular plexus of the retina occurs in three different stages. In the first
      stage (angioblast phase), during gestational weeks 6-7, mesenchymal precursor
      cells arising from the arterial and venous circle around the optic nerve invade
      the nerve fiber layer of the retina via the otic disc border. They form a network
      of angioblasts that gives rise to an immature capillary network in the second
      stage (angiogenesis phase). This vascular monolayer is located within the nerve
      fiber layer and reaches the ora serrata around gestational weeks 9-10. Initially,
      the immature retinal capillaries have an irregular appearance with wide lumina
      and relatively small intercapillary meshes. Subsequently, the lumina become
      smaller by involution and atrophy. In the third stage (maturation and remodeling
      phase) the immature blood vessels differentiate into retinal arterioles,
      capillaries and venules. From gestational week 11 onwards, the larger retinal
      arterioles are surrounded by a distinct periarteriolar capillary-free zone. The
      three stages start at the optic disc and extend centrifugally towards the retinal
      periphery. The development of the outer vascular plexus is essentially different
      from the angiogenesis of the inner vascular plexus. The outer retinal vessels
      that are located in the inner nuclear layer arise from previously developed
      capillaries and venules located in the inner vascular plexus. Moreover, the
      development of the outer vascular plexus starts at the macula and proceeds along
      with the maturation of the neural retina.

PMID- 8751111
TI  - Light and electron microscopical demonstration of methylene blue accumulation
      sites in taste buds of fish and mouse after supravital dye injection.
AB  - Electron microscopical data regarding methylene blue staining of taste buds in
      the epithelia of the goldfish lip and the cirumvallate papilla of the mouse
      tongue after supravital dye application are presented for the first time. The
      ultrastructural details were compared with the corresponding light microscopical
      findings. The dye was applied in different concentrations by injection or in
      crystalline from directly to the surface of the tissues. Both methylene blue and
      tissue were simultaneously fixed by immersion in a paraformaldehyde
      glutaraldehyde solution with the addition of phosphomolybdic acid. The ensuing
      dye precipitate was further stabilized by ammonium heptamolybdate. On the light
      microscopical level, the taste bud's receptive structures, i.e. the receptor area
      (fish) and the taste pit (mouse), exhibited the highest affinity for the dye.
      Additionally, the mucous material within the trenches around the circumvallate
      papillae in mice was intensely stained. On the electron microscopical level, the
      cationic phenothiazine dye bound to the receptor villi or to the mucus coating
      the receptive structures. In the case of higher dye concentrations, a staining of
      single taste bud cells took place starting apically and proceeding down to the
      base. Dye accumulations within the intercellular clefts between the epithelial
      cells or within other structures were observed only if the dye concentration was
      further increased. Since similar results were also obtained with the cationic
      phenazo dye Janus green, dye accumulation in the mucus covering the receptor
      villi may be representative of the general binding of organic cations, which are
      known to induce bitter taste sensations.

PMID- 8751112
TI  - Ontogeny, distribution and amine/peptide colocalization of chromogranin A- and B
      immunoreactive cells in the chicken gizzard and antrum.
AB  - The ontogeny and the distribution of chromogranin A (CgA)- and chromogranin B
      (CgB)-immunoreactive endocrine cells was studied in the chicken gizzard and
      gizzard-duodenal junction (also called pylorus or antrum) during embryonic and
      postnatal life. The same tissue sections were then double-immunostained to
      identify the CgA-and CgB-immunoreactive cells, with a panel of polyclonal
      antibodies raised against main gut amine/peptides. In the gizzard, positive cells
      were observed only in its two diverticula (proximal and distal caeca), where the
      first CgA- and CgB-immunoreactive cells were found on day 12 of incubation. They
      always remained moderate in number and co-stored mainly serotonin, gastrin/CCK
      and neurotensin. A few also co-stored somatostatin, but only during the embryonic
      period. Others co-stored PYY, but only after hatching. Co-localization with
      motilin was rare and never occurred with bombesin. In the chicken antrum, the
      first CgA- and CgB-immunoreactive cells were observed on day 12 of incubation and
      soon reached very high numbers. Antral positive cells showed almost the same co
      localization pattern as the gizzard diverticula. Despite their high chromogranin
      content, the antral cells had weak argyrophilia, whereas in the gizzard
      diverticula the two staining patterns corresponded.

PMID- 8751114
TI  - Myopia in teenagers. An eight-year follow-up study on myopia progression and risk
      factors.
AB  - A prospective 2-year study on myopia progression was commenced in 1984/85, with
      special attention to the rate of progression in a representative group of school
      children aged 9 to 12 years. A follow-up investigation of this group of myopic
      persons (now aged 17-20 years) was performed after 8 years, in order to describe
      the refractive error and possible risk factors for myopia progression over the
      period. The refractive error increased from -2.77 D to -5.14 D (mean values).
      PARAMETERS: age at debut, degree of myopia, intraocular pressure, changes at the
      fundus, status of phoria, nearpoint of convergence and accommodation were all
      measured at the start and related to the refractive error measured 8 years later.
      No single parameter, apart from age at debut, indicated that the individual would
      reach a high degree of myopia. The refractive error among the children with a
      debut below 7 years of age was -6.60 D, but only -3.72 D among those with a debut
      after 10 years. The change in refractive error over the 8-year period was not
      statistically related to the age at debut, neither did the rate of progression
      depend on the degree of myopia, the changes at the fundus, nor the intraocular
      pressure. However, children could be found who had a high rate of progression, by
      using a combination of these parameters.

PMID- 8751115
TI  - Myopia of adult onset. Can analyses be based on patient memory?
AB  - One hundred and fifty-one adult subjects (age 26-64 years) with simple myopia
      ('simple' = absence of significant astigmatism and anisometropia) were asked
      about their myopia onset, here defined as the age when first having spectacles to
      correct vision trouble for distance. A precise memory appeared in 148. Usually,
      they could substantiate their information by detailed accounts regarding how and
      when. Evidently, the first pair of glasses is a strong emotional experience.
      Accordingly, information appears to be reliable when properly asking the patient.
      The sample confirmed established knowledge: the earlier the onset, the higher the
      final myopia. Adult onset myopia is usually low, but occasionally intermediate or
      high myopia cases are encountered. Adult onset myopia appears more frequently
      than evident from textbooks and literature on refractive distribution. A
      frequency estimate based on Danish material thus suggests that at least 25-30% of
      all adult age myopia is also of adult onset.

PMID- 8751113
TI  - Postnatal development of the human primary motor cortex: a quantitative
      cytoarchitectonic analysis.
AB  - The postnatal development of the human primary motor cortex (area 4) was analyzed
      in 54 individuals ranging in age from birth to 90 years. Three parameters
      defining major cytoarchitectonic features (areal fraction, numerical density and
      mean area of cells) were measured in vertical columns extending from the pial
      surface to the border between cortex and underlying white matter. The data were
      compiled in profile curves that reveal or more detailed laminar pattern than the
      classical cytoarchitectonic descriptions. The most pronounced decreases in
      numerical density and areal fraction of Nissl-stained cells profiles during early
      postnatal ontogeny are observed in layer II. A clearly delineable layer IV, which
      is still recognizable in the newborn, disappears gradually during the first
      postnatal months. Although the width of the cortex as a whole increases during
      this period, layer V, the main source of pyramidal tract fibers, is the only
      lamina that also increases in relative thickness. The other layers remain stable
      or become relatively thinner. These results reveal specific laminar growth
      processes in area 4, which take place in parallel with the functional maturation
      of the cortical motor system.

PMID- 8751116
TI  - Adult onset myopia--oculometric features.
AB  - Adult onset myopia was investigated by ultrasound eye measurements and
      keratometry in 33 subjects (16 females, 17 males; age 32-62 years; age at myopia
      onset 18-50 years, mean value 26.2 years, SD 7.80). They were compared with 30
      subjects (15 females, 15 males; age 29-62 years) with myopia onset age 4-16 years
      (mean value 11.1 years, SD 2.89). Excluded were subjects with cataract and
      corneal pathology. In the adult onset group, myopia ranged a little lower than in
      early onset myopia (mean values -3.24 and -4.91 D, respectively), but high myopia
      was encountered in both groups (peak values -10 and -10.5 D). In both groups
      axial elongation was the main oculometric event. There was no evidence of a
      corneal/lenticular background in adult onset myopia. In accord with the higher
      myopia in the early onset group the eyes were also larger (as for axial and
      vitreous length, mid lens depth) than in those of adult onset. Adult onset myopia
      being axial of nature, the findings confirm what has been suggested from recent
      reports by other authors: that the eye has a potential for re-starting growth,
      even years after the presumed normal ocular growth arrest during early teenage
      years.

PMID- 8751117
TI  - Myopia of prematurity, clinical patterns. A follow-up of Danish children now aged
      3-9 years.
AB  - A discussion of myopia of prematurity is based on 16 low-birth weight children
      now aged 3-9 years. During their first months after delivery, retinopathy of
      prematurity had been observed in all but one subjects-here possibly missed due to
      incomplete control. Two subjects had cryotherapy. Two eyes out of 32 got blind;
      another 4 eyes became weak-sighted. The primary aim of the longitudinal study was
      to describe the variation in-and the course of-refraction, as apparent from
      serial examinations, the natural history so to say, to add new facets to our
      concept of myopia of prematurity and possibly to identify subgroups. Transient
      and fluctuating myopia being physiological in the first postnatal months, the
      diagnosis "myopia of prematurity' should not be forwarded too early. Some cases
      of early myopia which did not regress as usual over the first 6 months, later
      showed a reduction in degree of myopia over 1-2 years. Others pertained to the
      classical description of a stationary myopia, often of high degree, diagnosed in
      early childhood. Even in the favourable tail of the present distribution
      corrected visual acuity appeared subnormal according to age norms.

PMID- 8751119
TI  - Eye movements in normal subjects induced by vibratory activation of neck muscle
      proprioceptors.
AB  - Versional eye movements, induced by neck muscle vibration at 70 Hz in 8 normal
      subjects, were recorded with infrared reflection technique in each eye separately
      with one eye fixating a target and the other covered. The direction of eye
      movements was horizontal when the sternocleidomastoid muscle on one side of the
      neck and the splenius on the other side were activated, and downward when both
      splenii muscles were vibrated. The direction was the same as that of the illusory
      movements of the target also induced by the vibration. These findings would imply
      that the proprioceptive messages originating in the neck muscles are processed
      together with visual information of eye position in determining gaze direction.

PMID- 8751118
TI  - Correlating preferential looking visual acuity and visual behavior in severely
      visually handicapped children.
AB  - We developed a series of questions that reflects the functional abilities of
      severely visually handicapped children. The study population comprised 100
      patients aged 30 to 60 months (mean 43.23), mostly afflicted with retinopathy of
      prematurity. Visual acuity was measured by preferential looking. Preferential
      looking acuities of the patients ranged from 20/25 (0.8) to 20/6400 (0.003) (mean
      20/470 (0.04)). Ten activities were analyzed and correlated with preferential
      looking acuity. Among the selected visual activities, when children are not
      interested in television (p = 0.0001), toys (other than those that make sounds (p
      = 0.0001), and people (p = 0.001)), their preferential looking acuities were very
      low. For example, 73 out of 100 patients who were visually interested in
      television had preferential looking acuities (mean 20/245 (0.082)) that were
      significantly higher (p = 0.001) than 21 patients not interested in television
      (mean 20/2806 (0.007)). Patients with nystagmus (n = 79) had significantly lower
      preferential looking acuities (p = 0.0001) (mean 20/1114 (0.018)) than patients
      with no nystagmus (mean 20/57 (0.35)). When evaluating visual function in young,
      severely visually impaired patients, in addition to preferential looking testing,
      analyzing visual behavior within the environment is important to accurately
      evaluate their remaining visual abilities.

PMID- 8751120
TI  - Sensory adaptations in Duane's retraction syndrome.
AB  - Knowledge of the sensory status of patients with Duane's retraction syndrome is
      limited. Fourteen patients with type A Duane's retraction syndrome, aged 6 to 22
      years, were assessed prospectively and their sensory findings and the nature of
      their sensory symptoms detailed. All 14 patients had corrected monocular Snellen
      acuities of 6/9 or better. Six patients were asymptomatic and 5 of these had
      dense suppression on lateral versions, were free of diplopia and had variable
      stereopsis. The 5 bilateral cases were among the asymptomatic group. The
      remaining 8 patients had weak or absent suppression on lateral versions, variable
      horizontal diplopia and relatively normal stereopsis. Six were aware of diplopia
      but were never bothered by it and two spontaneously complained of symptoms
      related to abnormal binocularity (diplopia in one and asthenopia at near in
      both). It was not [corrected] possible to differentiate the 2 symptomatic cases
      from the former 6 on the basis of their sensory findings. Patients with type A
      Duane's retraction syndrome spontaneously complained of symptoms related to
      abnormal binocularity. The patients least likely to suffer sensory symptoms were
      bilateral cases or patients with dense suppression on lateral versions,
      irrespective of their stereoacuity levels.

PMID- 8751121
TI  - CO2 dependence of retinal arterial and capillary blood velocity.
AB  - OBJECTIVE: Blood flow to the brain is extremely sensitive to changes in PCO2.
      While animal studies show a similar potent PCO2 dependence in retinal and
      choroidal vessels, the PCO2-retinal blood flow relationship has never been
      adequately studied in humans. METHODS: Video scanning laser ophthalmoscopy after
      fluorescein angiography was used to analyze retinal arterial and capillary blood
      velocity under conditions of mild hypercapnia and hypocapnia. Control conditions
      (end-tidal PCO2 = 38.3 +/- 0.4 mmHg) were contrasted with hyperventilation
      induced hypocapnia (PCO2 = 34.0 +/- 0.4 mmHg) and hypercapnia (PCO2 = 42.3 +/-
      0.5 mmHg) created by PCO2 addition to inspired gas. RESULTS: Both larger vessel
      and macular capillary blood velocity was dependent upon PCO2: arteriovenous
      passage time fell as PCO2 rose, and both mean arterial dye velocity and capillary
      blood velocity rose as PCO2 rose (all p < 0.05). These changes in flow velocity
      occurred despite unchanged heart rate, arterial systolic and diastolic blood
      pressure, intraocular pressure, and calculated ocular perfusion pressure.
      Contrast sensitivity was also unchanged by PCO2 variation. CONCLUSIONS: The human
      retinal circulation, like the whole cerebral circulation, may be strongly
      dependent upon PCO2 in a manner that is unrelated to perfusion pressure and
      apparently outside strict autoregulatory controls.

PMID- 8751122
TI  - Increased levels of Epstein-Barr virus DNA in lacrimal glands of Sjogren's
      syndrome patients.
AB  - Many Sjogren's syndrome patients complain primarily of dry eye. Epstein-Barr
      virus DNA has recently been found in the lacrimal glands of Sjogren's syndrome
      sufferers and normal individuals, and lacrimal glands are thought to be a target
      organ for latent Epstein-Barr virus infection. In this study, we performed
      lacrimal and salivary gland biopsies on 9 Sjogren's syndrome patients. Extracted
      Epstein-Barr virus DNA was assayed by polymerase chain reaction and compared to
      that of healthy individuals. An increased level of Epstein-Barr virus DNA was
      observed in all of the lacrimal glands and 8 of the 9 salivary glands from the
      Sjogren's syndrome patients. However, the amount of genome in the lacrimal gland
      was more than 10 times that in the salivary glands, not only in the Sjogren's
      syndrome patients but also in the controls. This may explain the pathogenesis of
      dry eye in patients with Sjogren's syndrome, and why the lacrimal gland tends to
      be so prominently affected. It may also suggest a therapeutic approach for this
      and possibly other types of dry eye.

PMID- 8751123
TI  - Outcome monitoring in cataract surgery.
AB  - The short-term surgical results are reported in a consecutive series of 1473
      patients undergoing cataract surgery (60% planned extracapsular cataract
      extraction and 40% phacoemulsification) on an out-patient basis in a major
      university eye clinic. Preoperatively, 80% of all cases had a visual acuity of
      0.3 (6/18) or lower. On the first day after surgery, 51% of all patients had a
      corrected visual acuity of 0.5 (6/18) or better and 9% had a visual acuity of 1.0
      (20/20) or better. The unaided visual acuity was 0.5 (6/12) or better in 20% of
      all patients (78% of these after phaco-emulsification). The average postoperative
      refraction was -0.43 D (+/- 1.03 D SD, range -6.00 D to +5.00 D). A significant
      improvement in refractive error was achieved in many patients. The mean
      intraocular lens power prediction error was found to be +0.04D (+/- 0.84D). The
      surgically induced astigmatism (vector analysis) was found to be +4.91D (+/-
      2.08) in the extracapsular cataract extraction cases and +1.37D (+/- 1.38) in the
      phacoemulsification cases (p < 0.001). Capsular or zonular rupture and/or
      vitreous loss occurred in 43 (2.9%) of which 26 (1.8%) received an anterior
      chamber lens rather than the intended posterior chamber lens. The results of this
      study document the favorable results of modern cataract surgery.

PMID- 8751124
TI  - Socio-demographic trends in ocular cysticercosis.
AB  - There has been a gradual change in the socio-demographic trends of ocular/adnexal
      cysticerosis. We present the results of a 5-year study of 33 cases of
      ocular/adnexal cysticercosis and compare our observations with those reported by
      previous authors. The male:female ratio in our study was 2:1 and maximum number
      of patients (45%) belonged to the age-group of 31-40 years. Seventy percent of
      our patients were of low socio-economic status and 70% were strictly vegetarians.
      The most common location of cysticerci was in the vitreous (50% of all cases);
      orbital cysts were present in 5% and subconjunctival cyst in 3%. Most common
      extraocular site for associated cysticercosis was the brain (18%):
      Ultrasonography proved to be an effective and economical alternative to magnetic
      resonance imaging and computerized tomographic scanning for the detection of
      cysticerci in the orbit and in eyes with hazy media.

PMID- 8751125
TI  - The use of perfluorocarbon liquids in vitreoretinal surgery.
AB  - Two perfluorocarbon liquids (perfluoro-n-octane and perfluorodecaline) were
      evaluated as technical aids in vitreoretinal surgery in 42 patients.
      Perfluorocarbon liquids were found to stabilize the retina and simplify removal
      of repiretinal membranes, which in many cases permitted the subsequent use of an
      expanding gas instead of silicone oil at the conclusion of the operation. The
      infusion of a perfluorocarbon liquids allowed the drainage of subretinal fluid
      through peripheral retinal breaks obviating the need for a retinotomy in most
      cases. No difference could be observed between the two types of perfluorocarbon
      liquids, and there were no adverse effects associated with their use. The retina
      was centrally attached in 32 eyes (76%) at 3-10 months follow-up.

PMID- 8751126
TI  - Ultrasonographic findings in endophthalmitis.
AB  - Ultrasonographic findings are reported in 7 cases of endophthalmitis (6 of
      bacterial and 1 of fungal origin) resulting from perforating injuries (2 cases),
      severe corneal ulcers (2 cases) and open-eye surgery (3 cases). The most frequent
      ultrasonographic picture was characterized by a series of low reflectivity echoes
      in the vitreous with a high degree of mobility (7/7), fairly large endovitreal
      vacuoles (3/7) and hyaloid thickening (3/7). In one case the vitreous involvement
      was confined to only one quadrant. Choroidal thickening both of a homogeneous
      diffuse (2/7) and nodular-multifocal type (3/7) was found. Localized choroidal
      detachment (1/7) and exudative pre-equatorial retinal detachment (1/7) were
      detected in only two cases. Ultrasonography proved useful both for detecting
      involvement of the posterior segment and for monitoring the time course of the
      infection process.

PMID- 8751127
TI  - Retinal choroidal anastomosis in classic choroidal neovascularization
      demonstrated by indocyanine green angiography.
AB  - Pathologic retinal choroidal anastomoses are relatively rare. Until now, they
      have been described in age-related macular degeneration only in occult pigment
      epithelial detachments or following fibrous scarring. We report the occurrence of
      a retinal choroidal anastomosis with blood flow from an actively proliferating
      classic choroidal neovascular membrane into a retinal vein in a 72-year-old male
      with age-related macular degeneration. Indocyanine green videoangiography
      performed by scanning laser ophthalmoscope demonstrated the anastomosis, whereas
      it could not be identified clinically or with fluorescein videoangiography.

PMID- 8751128
TI  - Differential diagnosis of choroidal melanomas and nevi using scanning laser
      ophthalmoscopical indocyanine green angiography.
AB  - Fluorescein angiography is one of several standard ancillary diagnostic
      techniques in the evaluation of suspected malignant choroidal melanoma.
      Indocyanine green choroidal angiography has improved visibility of the choroidal
      circulation in comparison with fluorescein angiography. Studies concerning the
      use of indocyanine green angiography in the differentiation between nevi and
      melanomas have been few and the results inconclusive. A case of a choroidal
      melanoma (verified by histopathological examination) and a nevus in the same eye
      is documented by fluorescein and indocyanine green choroidal angiography
      performed by scanning laser ophthalmoscopy. This modality may be considered in
      the evaluation of a suspected malignant choroidal melanoma.

PMID- 8751129
TI  - Orbital presentation of ethmoid sinus adenocarcinoma.
AB  - Ethmoid sinus adenocarcinoma with orbital invasion is distinctly uncommon. This
      case presented with epiphora, whereas proptosis and decreased ocular motility
      were later signs. Treatment was delayed for 4 months, while misdiagnoses like
      dacryocystitis and thyroid eye disease were entertained. Even an incisional
      biopsy was not sufficient for a conclusive diagnosis and adenomatous
      differentiation was only present in a small proportion of tissue available after
      an excisional attempt. The aggressive behaviour including this patient's death of
      metastatic disease, underlines the importance of considering secondary invasion
      from a sino-nasal malignancy in uncharacteristic orbital disease.

PMID- 8751130
TI  - Subretinal tumour in a patient with a limited form of Wegener's granulomatosis.
AB  - In 1939 F. Wegener published a report concerning a peculiar febrile syndrome with
      necrotizing inflammation of the upper respiratory tract, focal glomerulonephritis
      and systemic angiitis (Wegener 1939). Clinically Wegener's granulomatosis can be
      divided into a limited and a generalized form. We describe a patient presenting
      with unilateral ocular symptoms suspicious of a neoplasm, one episode of angina
      pectoris and general malaise without any clinical signs of upper respiratory
      tract involvement. Before Wegener's granulomatosis was diagnosed by a positive
      titre of antineutrophil cytoplasmic antibodies and open lung biopsy,
      immunoscintigraphy for malignant melanoma showed a false positive result.
      Systemic treatment with corticosteroids and cyclophosphamide resulted in an
      improvement of the ocular symptoms within weeks.

PMID- 8751131
TI  - Squamous spindle cell carcinoma of the conjunctiva. Fatal outcome of a plerygium
      like lesion.
AB  - Squamous spindle cell carcinoma of the conjunctiva is an infrequent entity that
      behaves distinctly different from "ordinary' squamous cell carcinoma. This case
      report reviews the clinical and histopathological features of a lesion, that
      despite an insidious clinical appearance caused the patient's death 14 months
      following the initial excision. Data from previous reports are outlined.

PMID- 8751132
TI  - Aspergillus fumigatus scleritis.
AB  - We report a case of scleritis caused by Aspergillus fumigatus. The infection was
      successfully treated with antifungal drugs, cryotherapy and dura mater grafting.
      A 67-year-old man developed a scleral ulcer 2 months after suffering a trauma in
      his right eye caused by the branch of a tree. Diagnosis was made after biopsy of
      a scleral nodule. Scrapings showed hyphal fragments and cultures were positive
      for Aspergillus fumigatus. Although therapy with oral fluconazol and topical
      amphotericin B was begun, the scleritis continued to worsen, so cryotherapy and
      dura mater grafting were performed. The patient showed no signs of infection for
      8 months after discontinuation of antifungal drugs.

PMID- 8751133
TI  - Odontogenic orbital cellulitis. Report of a case and considerations on route of
      spread.
AB  - A case of orbitral cellulitis following dental extraction is described. Orbital
      extension of infection occurred via the retromaxillary infra-temporal fossa,
      which is an unusual feature.

PMID- 8751135
TI  - Learning phaco: self-sealing incision in phaco.

PMID- 8751134
TI  - An instrument for recording the ocular pulse wave.
AB  - An instrument for recording the ocular pressure pulse is described. Examples of
      recordings showing individual differences in the shape of the pulse curve are
      demonstrated. The properties of the instrument as to the frequency response in
      the range 0.5-10 Hz are established with the aim of correcting the recordings for
      instrumental errors.

PMID- 8751136
TI  - Force development and velocity of saccadic eye movements in normal subjects and
      strabismic patients.

PMID- 8751137
TI  - Molecular mechanisms of virus-induced carcinogenesis: the interaction of viral
      factors with cellular tumor suppressor proteins.
AB  - Accumulating evidence indicates that tumor viruses represent a major etiological
      factor in a significant portion of human cancers. These cancers include human
      papillomavirus induced anogenital cancers, hepatitis B and C virus associated
      hepatocellular carcinomas, nasopharyngeal carcinomas and lymphomas linked to
      Epstein-Barr virus infection, and human T cell leukemia virus associated adult T
      cell leukemias. This review summarizes the recent progress made in understanding
      the molecular mechanisms of viral carcinogenesis, with a particular focus on the
      interaction of viral factors with cellular tumor suppressor proteins. The
      functional inactivation of tumor suppressor proteins may represent a common
      strategy by which several tumor viruses contribute to malignant cell
      transformation.

PMID- 8751139
TI  - DNA diagnosis of human genetic individuality.
AB  - DNA studies of the human genome have shown polymorphic variation at thousands of
      sites, defining an absolute genetic uniqueness for each individual. There are
      many circumstances in which it may be desirable to diagnose this molecular
      individuality, as for instance, in criminal investigations or paternity testing.
      Several techniques can be used for this DNA diagnosis and we can choose among
      them the one that best suits the specific problem at hand. In this review we
      describe the main methodologies in current use to investigate human DNA
      polymorphisms, discussing the best application of each option, as well as their
      advantages and disadvantages.

PMID- 8751140
TI  - Molecular analysis at the Harvey Ras-1 gene in patients with long QT syndrome.
AB  - Patients with long QT syndrome (LQTS; MIM 1921500) frequently suffer from syncope
      and are threatened by sudden cardiac death due to ventricular arrhythmias,
      typically of the torsade de pointes type. Initial progress in revealing the
      molecular basis of the disease was made by the observation of genetic linkage of
      the disease locus to the Harvey Ras-1 gene (HRAS 1) on chromosome 11p15.5. More
      recently loci on chromosomes 3, 4, and 7 have also been found to be linked to
      LQTS, thus demonstrating heterogeneity in the causes for this disease. The
      present study performed sequence analysis on the HRAS 1 gene in patients with
      congenital and acquired LQTS to determine the frequency of HRAS 1 mutations in
      patients with this disease. In neither group were no mutations identified in the
      coding regions or in the splice donor and acceptor sites. Alleles characterized
      by a T to C transition in exon 1 and an insertion/deletion polymorphism upstream
      of exon 1 showed no significant difference in their frequencies between LQTS
      patients and normal controls. No quantitative influence of the such characterized
      genotypes on the QT duration was observed. These results demonstrate that
      structural mutations in the HRAS 1 gene are not a frequent cause of LQTS. Also,
      since there was no association of different alleles at the HRAS 1 locus with
      changes in QT duration, it appears unlikely that this gene is a major contributor
      to this disease.

PMID- 8751141
TI  - Expression of osteoblastic markers in cultured human bone and fracture callus
      cells.
AB  - We compared the expression of osteoblastic markers in cultured human cells
      isolated from fracture calluses of various histological states of development
      with that in cells from adult and fetal bone. Adult osteoblasts and all callus
      cells produced almost exclusively type I collagen, whereas fetal osteoblasts
      produced also considerable amounts of type III collagen in vitro. 1,25
      Dihydroxyvitamin D3 induced the synthesis of osteocalcin in all bone and callus
      cells but to varying extents. Fetal bone cells and early-stage callus cells
      synthesized less than 10% the amount of osteocalcin produced by adult bone cells.
      Late-stage callus cells produced intermediate levels of osteocalcin. Fetal bone
      cells and early-stage callus cells responded to parathyroid hormone with a less
      pronounced increase in intracellular cAMP than did adult bone cells. Late-stage
      callus cells showed the best response to parathyroid hormone. The activity of
      alkaline phosphatase was highest in fetal bone cells. These observations show
      that cells isolated from fetal bone and from fracture callus tissues express a
      pattern of markers clearly relating them to the osteoblastic lineage. On the
      basis of the different patterns of osteoblastic markers expressed in vitro we
      conclude that functionally distinct subtypes of osteoblasts do exist in different
      mineralized tissues and at different developmental stages.

PMID- 8751143
TI  - Astute observers discover anti-asthma drugs.

PMID- 8751142
TI  - Messenger RNA expression for a TSH receptor variant in the thymus of a two-year
      old child.
AB  - We recently described the presence of a thyroid-stimulating hormone receptor (TSH
      R) variant in orbital tissues. Although the presence of this TSH-R variant could
      provide the antigenic link between the thyroid and the orbit in Graves' disease
      and thyroid-associated ophthalmopathy (TAO), the etiopathophysiological
      significance of this finding remains to be elucidated. Graves' disease and TAO
      are autoimmune diseases which are likely to be caused by a breakdown of
      tolerance. We therefore investigated the presence of this variant TSH-R
      transcript in human thymus. Using primers specific for this variant in reverse
      polymerase chain reaction (PCR) experiments, Southern blotting, and sequencing of
      the PCR products we demonstrate the presence of this transcript in RNA extracted
      from normal human thymus of a 2-year-old child. We were also able to amplify this
      variant TSH-R transcript from a normal human thyroid cDNA library, but not from
      an epithelial thymus library. The presence of the variant TSH-R transcript in RNA
      prepared from normal human thymus suggests that induction of immunological
      tolerance against this variant TSH-R transcript in the thymus is possible. A lack
      of tolerance induction for this variant TSH-R transcript could provide an
      explanation for a possible antigenic link between Graves' disease and TAO.

PMID- 8751144
TI  - The research behind terbutaline.

PMID- 8751145
TI  - Factors behind the functional beta 2-adrenoceptor selectivity of terbutaline.

PMID- 8751138
TI  - Molecular basis of polymorphic drug metabolism.
AB  - Genetic polymorphisms with functional effects occur in many of the genes encoding
      drug metabolizing enzymes and are an important cause of adverse drug reaction.
      Recent advances in the understanding of the molecular genetics of drug
      metabolizing enzymes, particularly the cytochromes P450, has enabled the
      molecular basis of several polymorphisms to be elucidated and genotyping assays
      using the polymerase chain reaction to be developed. Polymorphisms in this
      category include those in the cytochrome P450 genes CYP2D6, CYP2C19, CYP2A6,
      CYP2C9 and CYP2E1, the glutathione S-transferase genes GSTM1 and GSTT1 and the N
      acetyltransferase gene NAT2. The molecular basis and importance to drug
      metabolism of the various polymorphisms as well as evidence for the existence of
      polymorphisms in other genes encoding drug-metabolizing enzymes such as the UDP
      glucuronosyltransferases, the sulphotransferases and the methyltransferases are
      discussed.

PMID- 8751146
TI  - beta-Adrenoceptor agonists after terbutaline.

PMID- 8751147
TI  - Terbutaline prodrugs and oral beta 2-agonist therapy.

PMID- 8751149
TI  - beta-Adrenoceptor agonists in future asthma therapy.

PMID- 8751148
TI  - Turbuhaler drugs involving terbutaline and other compounds.

PMID- 8751150
TI  - [International Journal of Food Research and Technology].

PMID- 8751151
TI  - Growth profiles and articular cartilage characterization in a goat model of Legg
      Calve-Perthes disease.
AB  - Numerous animal species, including the goat, have been evaluated as potential
      models for human Legg-Calve-Perthes disease (LCPD). These models disrupt the
      vasculature of the femoral head, causing it to collapse, and therefore do not
      mimic all the clinical patterns of the human disease. Baseline data regarding the
      weight and femoral length in the growing goat are not available. This study
      characterized the goat's normal growth for comparison with that of humans. The
      growth aberrations in the proximal femur created by surgically ablating the
      capital physis were described and compared with the aberrations observed in human
      LCPD cases. Age, weight, and femoral length (test and control) data were obtained
      for goats approximately 1 to 14 months of age. At 4 months of age, a
      craniolateral surgical approach was used to expose the cranial lateral capital
      physis so that it could be cauterized. Postoperative radiographs were evaluated
      by graphic analysis to assess the resultant changes in the morphology of the
      proximal femur. The articular cartilage of the femoral head and acetabulum was
      evaluated mechanically, using indentation testing, to determine the apparent
      modulus of elasticity, and histopathologically regarding its thickness and
      proteoglycan content. The proximal femurs of goats and humans exhibit similar
      morphology and growth patterns. There was a positive correlation between age,
      weight, and femoral lengths in the goat. The surgical procedure was effective in
      ablating the capital femoral physis as indicated by shorter femoral lengths and
      fragmented, flattened, and mushroomed femoral heads. The histopathological data
      revealed that the articular cartilage was significantly thicker in the operated
      hip joints at the ventrocaudal and cranial acetabula and the dorsal and ventral
      femoral heads. The test cartilage exhibited significantly less positive staining
      for proteoglycans in the dorsocaudal and the cranial acetabula as well as the
      ventral femoral head. The apparent modulus of elasticity, of the test cartilage
      was significantly lower than the control value at the dorsocaudal acetabulum.
      These data show that the surgical procedure produced morphological changes that
      mimic those in human LCPD. The increased thickness of the articular cartilage of
      the LCPD femoral head may account for the articular degeneration observed in
      older patients with LCPD, as increased cartilage thickness is associated with
      decreased tissue quality.

PMID- 8751152
TI  - Analysis of vocal fold function in the miniswine model.
AB  - Correlation of the vocal fold vibratory pattern with the postoperative surgical
      wound should demonstrate to the laryngologist the critical depth of injury at
      which the functional voice would be adversely affected. An animal model was
      selected to study these changes. Twelve adult miniswine were operated on in this
      prospective study. The right true vocal fold was surgically altered; the left
      true vocal fold was the control. An interval of 6 weeks was allowed for healing,
      and then changes in vocal fold function were studied by stroboscopy, photography,
      voice recording, and electroglottography. Laryngectomy provided tissue for
      histopathological correlation. The results showed that injury at the junction of
      the lamina propria and vocalis muscle consistently caused significant vibratory
      dysfunction resulting in poor phonation.

PMID- 8751153
TI  - A novel technique for long-term vascular access in the unrestrained rat.
AB  - A new system for long-term vascular access in the unrestrained rat (n = 380) is
      described that combines low cost with high reliability and free movement. It
      consists of a polyurethane catheter that is placed in the right atrium via the
      external jugular vein. A leather harness is applied to the animal and the
      catheter passed subcutaneously to the neck into the harness. The harness is
      connected to the outside of a swivel joint via a silicone tube in which the
      catheter runs. The catheter is connected to the inside of the swivel. The swivel
      is a modified conventional 5-mL glass syringe and is positioned in ball bearings
      and a Johnson joint. Swivel, ball bearings, and the Johnson joint are
      counterbalanced and can move up and down. With this system all catheters
      functioned well until they were electively removed after 28 days. Four catheter
      dislocations resulted from harness failure and three from a twisted catheter.
      Seven cases of septicemia and eight of thrombosis occurred. All animals gained
      weight (3.53 +- 0.37 [SEM] g/d) during the time the system was in place. The
      entire apparatus is simple and inexpensive to construct. The rotary portion of
      the swivel and the Johnson joint avoid twisting of the catheter, and the
      counterbalance enables the animal to move up and down. The low thrombogenicity of
      polyurethane further reduced complications. This system reduces stress for the
      animal during long-term investigations.

PMID- 8751154
TI  - Pulmonary arterial contribution to airway blood flow after lung transplantation
      in dogs.
AB  - Despite the improved success of lung transplantation, ischemia of the donor
      bronchus continues to be the most important factor influencing airway healing.
      Recent studies have shown that at the level of the mainstem bronchi the pulmonary
      contribution to the airway blood flow may be equivalent to or greater than the
      systemic contribution and could therefore assist early healing of the newly
      anastomosed bronchus and, in addition, might facilitate the improved healing
      associated with omentopexy. The aim of this study was to measure the pulmonary
      contribution to airway blood flow in dogs after allotransplantation of the left
      lung and to determine whether omentopexy might improve the healing process. Using
      the radioactive microsphere technique, we measured the pulmonary contribution to
      airway blood flow in 25 dogs 1 week after allotransplantation of the left lung.
      Half the dogs had an omental wrap around the anastomotic site. Results showed
      that pulmonary blood flow increased progressively from lower trachea to distal
      mainstem bronchus and supplied the left mainstem bronchus above as well as below
      the anastomotic site. Omentopexy did not increase flow or enhance healing.

PMID- 8751155
TI  - Glutamine metabolism in AS-30D hepatoma cells. Evidence for its conversion into
      lipids via reductive carboxylation.
AB  - A study was undertaken to assess the role of a physiological concentration of
      glutamine in AS-30D cell metabolism. Flux of 14C-glutamine to 14CO2 and of 14C
      acetate to glutamate was detected indicating reversible flux between glutamate
      and TCA cycle alpha-ketoglutarate. These fluxes were transaminase dependent. A
      flux analysis was compared using data from three tracers that label alpha
      ketoglutarate carbon 5, [2-14C]glucose, [1-14C]acetate and [5-14C]glutamine. The
      analysis indicated that the probability of flux of TCA cycle alpha-ketoglutarate
      to glutamate was, at minimum, only slightly less than the probability of flux of
      alpha-ketoglutarate through alpha-ketoglutarate dehydrogenase. The apparent Km
      for oxidative flux of [14C]glutamine to 14CO2, 0.07 mM, indicated that this flux
      was at a maximal rate at physiological, 0.75 mM, glutamine. Although oxidative
      flux through alpha-ketoglutrate dehydrogenase was the major fate of glutamine,
      flux of glutamine to lipid via reductive carboxylation of alpha-ketoglutarate was
      demonstrated by measuring incorporation of [5-14C]glutamine into 14C-lipid. In
      media containing glucose (6 mM), and glutamine (0.75 mM) 47 per cent of the lipid
      synthesized from substrates in the media was derived from glutamine via reductive
      carboxylation and 49 per cent from glucose. These findings of nearly equal fluxes
      suggest that lipogenesis via reductive carboxylation may be an important role of
      glutamine in hepatoma cells.

PMID- 8751156
TI  - The different inhibiting effect of cholera toxin on two leukemia cell lines does
      not correlate with their toxin binding capacity.
AB  - The murine leukemia cell lines L1210 and WEHI-3B show a very different
      sensitivity to the cholera toxin (CT). The in vitro growth of L1210 is completely
      inhibited by 10(-8) M CT, while WEHI-3B growth shows the same inhibition at 10(
      11) M. The analysis of membrane ganglioside pattern of the two cell lines shows
      that in L1210 cells the major component is the GM1a ganglioside while the
      monosialogangl oside fraction from WEHI-3B is entirely composed of gangliosides
      of the 'b' series among which GM1b is the more represented. The total cholera
      toxin binding capacity of the ganglioside extract from L1210 cells is more than
      hundred fold higher than that of WEHI-3B and this difference is also confirmed by
      the number of CT receptors/cell and by the binding of FITC-B subunit of CT on the
      cells. These surprising data are in conflict with the poor sensitivity to CT
      evidenced by L1210 compared to WEHI-3B cells. In order to clarify this
      discrepancy we investigated the cAMP accumulation, the cell viability and the
      clonogenicity of these two leukemia cell lines following the treatment with CT
      and forskolin (FRSK). The treatment of WEHI-3B cells with CT induces a dramatic
      increase of intracellular cAMP which highly correlates with cell death and the
      decrease of clonogenicity and this result is partially obtained by the treatment
      with FRSK. L1210 cells do not evidence significant cAMP accumulation neither with
      CT nor with FRSK treatment. These data suggest that the different inhibiting
      effect of CT on WEHI-3B and L1210 cells does not correlate with their different
      pattern of gangliosides and the related toxin binding capacity. Further they
      indicate that the growth inhibition of WEHI-3B cells is closely related with a
      cAMP-dependent cell killing mechanism, while the inhibition of L1210 growth
      (produced by high concentration of CT) is mediated by a cAMP independent
      mechanism.

PMID- 8751157
TI  - Enhanced expression of GTP-binding proteins in differentiated U937 monocytic
      cells: possible involvement of tyrosine kinase and protein kinase C.
AB  - Monocytic U937 cells were differentiated into mature macrophages in the presence
      of 100 nM phorbol 12-myristate 13-acetate (PMA) for 24 h at 37 degrees C. We
      investigated the alterations in the expression of GTP-binding proteins that take
      place during differentiation of these cells. A 40 KDa alpha-subunit of the
      inhibitory G-protein was identified by specific antibodies to Gi alpha-1/2 and Gi
      alpha-3 on Western blots and also by ADP-ribosylation catalyzed by pertussis
      toxin. The expression of the 40 KDa Gi alpha subunit was increased 3.4 fold in
      differentiated cells. The expression of a 43 KDa Gs alpha subunit identified by
      Western blotting using specific antibody to Gs alpha and by ADP-ribosylation in
      the presence of cholera toxin was increased approximately 2 fold in
      differentiated cells. A faintly recognizable 46 KDa Gs alpha subunit was also
      increased but to a lesser extent (1.3 fold). Small molecular weight GTP-binding
      proteins identified by [35S]GTP gamma S binding on nitrocellulose blots were also
      increased significantly. The PMA-induced expression of Gi alpha-1/2 and Gs alpha
      subunits was blocked to control level by both genistein and staurosporine,
      inhibitors of protein tyrosine kinase and protein kinase C, respectively.
      However, staurosporine was unable to block the PMA-induced expression of Gi alpha
      3; this was blocked only by genistein. These data suggest a role for tyrosine
      kinase and protein kinase C in the expression of G-proteins during
      differentiation of U937 cells.

PMID- 8751158
TI  - Characterization of the phosphatidylinositol-specific phospholipase C-released
      form of rat osseous plate alkaline phosphatase and its possible significance on
      endochondral ossification.
AB  - Alkaline phosphatase activity was released up to 100% from the membrane by
      incubating the rat osseous plate membrane-bound enzyme with phosphatidylinositol
      specific phospholipase C. The molecular weight of the released enzyme was 145,000
      on Sephacryl S-300 gel filtration and 66,000 on PAGE-SDS, suggesting a dimeric
      structure. Solubilization of the membrane-bound enzyme with phospholipase C did
      not destroy its ability to hydrolyse PNPP, ATP and pyrophosphate. The hydrolysis
      of ATP and PNPP by phosphatidylinositol-specific phospholipase C-released enzyme
      exhibited 'Michaelian' kinetics with K0.5 = 70 and 979 microM, respectively. For
      pyrophosphate, K0.5 was 128 microM and site-site interactions were observed (n =
      1.4). Magnesium ions were stimulatory (K0.5 = 1.5 mM) and zinc ions were a
      powerful noncompetitive inhibitor (Ki = 6.2 microM) of phosphatidylinositol
      specific phospholipase C-released enzyme. Phosphatidylinositol-specific
      phospholipase C-released alkaline phosphatase was relatively stable at 40 degrees
      C. However, with increasing temperature from 40-60 degrees C, the enzyme was
      inactivated rapidly following first order kinetics and thermal inactivation
      constants varied from 5.08 x 10(-4) min-1 to 0.684 min-1. Treatment of
      phosphatydilinositol-specific phospholipase C-released alkaline phosphatase with
      Chellex 100 depleted to 5% its original PNPPase activity. Magnesium (K0.5 = 29.5
      microM), manganese (K0.5 = 5 microM) and cobalt ions (K0.5 = 10.1 microM)
      restored the activity of Chelex-treated enzyme, demonstrating its metalloenzyme
      nature. The stimulation of Chelex-treated enzyme by calcium ions (K0.5 = 653
      microM) was less effective (only 26%) and occurred with site-site interactions (n
      = 0.7). Zinc ions had no stimulatory effects. The possibility that the soluble
      form of the enzyme, detected during endochondral ossification, would arise by the
      hydrolysis of the Pl-anchored form of osseous plate alkaline phosphatase is
      discussed.

PMID- 8751159
TI  - Molecular remodelling in hypertrophied hearts from polyomavirus large T-antigen
      transgenic mice.
AB  - Polyomavirus large T-antigen transgenic mice develop cardiac hypertrophy
      characterized by an increase in atrial natriuretic factor and beta-myosin heavy
      chain isoform expression. The aim of this study was to examine changes in proto
      oncogene expression in hypertrophied hearts from the transgenic mice. Expression
      of early growth response-1 (Egr-1) mRNA was detected in hearts from all 15
      transgenic mice, but was not detectable in 13 control mice. Reverse transcriptase
      polymerase chain reaction experiments using Egr-1-specific primers confirmed the
      increase in Egr-1 mRNA in enlarged hearts from the transgenic mice. Expression of
      c-jun, junD and Ha-ras mRNAs was increased in the transgenic hearts 3, 17 and 2.8
      fold respectively. Western blots showed an increase in c-myc, c-jun and ras
      protein in hypertrophied transgenic hearts. Immunofluorescence analyses confirmed
      an increase in Egr-1 and c-jun protein in transgenic cardiomyocytes.
      Proliferating cell nuclear antigen, Ki-ras and HSP 90 mRNAs were decreased 22,
      2.7 and 3-fold, respectively in the transgenic hearts. Not altered in most
      hypertrophied hearts was expression of c-fos, junB, p53, c-neu, c-myc, HSP70,
      HSP27, TGF-beta or IGF 1 mRNAs. Proto-oncogene and growth factor gene expression
      in hypertrophy induced by PVLT expression is modulated with some proto-oncogenes
      increased and others decreased in expression.

PMID- 8751160
TI  - Myristoylation of endothelial cell nitric oxide synthase is important for
      extracellular release of nitric oxide.
AB  - Endothelial cell nitric oxide synthase (NOS) is known to have a N-myristoylation
      consensus sequence. Such a consensus sequence is not evident in the macrophage,
      smooth muscle and neuronal NOS. A functional role for this N-terminal
      myristoylation is not clear yet. In the present study, we examined the effect of
      N-terminal myristoylation on the NOS activity determined by the conversion of L
      [3H]arginine to L-[3H]citrulline and extracellular NO release determined by
      nitrite production in the conditioned medium from the COS-7 cells transfected
      with wild-type bovine aortic endothelial cell (BAEC) NOS cDNA or non
      myristoylated BAEC-NOS mutant cDNA. NOS activity of wild type BAEC-NOS in COS-7
      cells was localized in the particulate fraction and that of mutant NOS was in the
      cytosolic fraction. In contrast, nitrite production from COS-7 cells transfected
      with wild type BAEC-NOS cDNA was greater than that of mutant cDNA in a time
      dependent and a concentration dependent manner. These results suggest that
      membrane localization of NOS with myristoylation facilitates extracellular
      transport of NO and leads to enhanced NO signaling on the vascular smooth muscle
      cells and the intravascular blood cells including neutrophils, macrophages and
      platelets.

PMID- 8751162
TI  - Quantitative contribution of the acid production to the intracellular
      acidification in human neutrophils stimulated by N-formyl-methionyl-leucyl
      phenylalanine.
AB  - A chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (fMLP), induced an
      acidification of cytosol by about 0.05 pH units in 30 sec followed by an
      alkalinization in human neutrophils. The quantitative contribution of acid
      production to the acidification was studied. The superoxide (O2-) production
      stimulated by fMLP was not involved in the acidification because the production
      of acids in neutrophils from patients with chronic granulomatous disease who do
      not produce O2-, was the same as that in normal neutrophils. The intracellular
      acidification was completely inhibited by deoxyglucose, suggesting that energy
      metabolism enhanced upon stimulation by fMLP might be the main source of the
      acidification. Although enhancement of the lactate formation by fMLP was 0.8
      nmol/10(6) cells, which could lower intracellular pH by 0.08 pH units, the
      lactate production could not explain the initial acidification because the
      production of lactate started at 1 min after the stimulation while the
      intracellular acidification began immediately after the stimulation.
      Mitochondrial respiratory inhibitors such as KCN and rotenone had no effects on
      the fMLP-induced intracellular acidification. The fMLP-induced production of CO2
      in 30 sec through the hexose monophosphate shunt was only 2.6 pmol/10(6) cells,
      which was calculated to decrease intracellular pH by only 0.0014. Thus, changes
      of energy metabolism induced by fMLP does not explain the acidification.

PMID- 8751164
TI  - Levels of superoxide dismutase mRNA in rat lens: effect of aging.
AB  - Superoxide dismutase, the enzyme catalyzing the dismutation of O2.- to H2O2 is
      known to be present in various ocular and nonocular tissues. In this
      communication we have determined the gene expression of this enzyme in rat
      lenses. The investigations have been conducted as a function of age using RNase
      protection assay. These in vitro assays for the corresponding mRNA suggested that
      the transcription of the gene is age variant, increasing as a function of age.
      The levels were significantly lower in the young lenses in comparison to the
      older lenses.

PMID- 8751161
TI  - Interferon modulates the messenger RNA of G1-controlling genes to suppress the G1
      to-S transition in Daudi cells.
AB  - Interferon (IFN) is one of the potent antiproliferative cytokines and is used to
      treat some selected cancers. IFN arrests the growth of Burkitt Lymphoma derived
      cell line Daudi cells in the G1 phase. G1-to-S progression is controlled by
      positive and negative regulatory genes. Therefore, we investigated the effects of
      IFN on G1-controlling genes. Expression of cyclin-dependent kinases (Cdks 2, 3,
      4, 5, 6), MO15/Cdk7, and cyclins E and H was studied to assess positive
      regulators, while p15Ink4B, p16Ink4, p18, p21Cip1, and p27Kip1 were assessed as
      negative regulators. Cdks 2, 4, 6 and cyclin E were markedly down-regulated.
      MO15/Cdk7 expression showed little change, but its regulatory subunit (cyclin H)
      was down-regulated like cyclin E. Expression of p15Ink4B and p16Ink4 was not
      observed. p18 was induced until 48 h and its expression returned to the initial
      level at 72 h. In contrast, p21Cip1 mRNA expression remained at the baseline
      level throughout IFN treatment, while the expression of p27Kip1 increased at 48
      and 72 h. Taken together, these data indicate that IFN changes the messenger RNA
      of G1-controlling genes towards the suppression of G1-to-S transition.

PMID- 8751163
TI  - Hyperplasia in the rabbit bladder urothelium following partial outlet
      obstruction. Autoradiographic evidence.
AB  - Previous experiments have shown that adult male rabbits subjected to partial
      outlet obstruction or overdistension and acutely labeled, 24 h later, in vivo or
      in vitro with 3H-Thymidine(3H-TdR) show high levels of incorporated radioactivity
      in bladder epithelium when they are visualized with autoradiography. To test the
      hypothesis that such labeling represents the onset of a wave of proliferation
      (that is, true hyperplasia), we injected 3H-TdR subcutaneously in two normal and
      three partially obstructed New Zealand White male rabbits on each of days One,
      Two or Three following obstruction. Bladders were excised on the seventh day(D)
      following obstruction or the sixth day after injection of normals. Under these
      conditions, cells labeled with 3H-TdR had the opportunity to proliferate, after
      labelling, for 6(OneD and Normals), 5(TwoD) or 4(ThreeD) days respectively. After
      processing tissues for autoradiography, normal bladders showed only trace levels
      of labeling. Animals exposed to 3H-TdR one day after obstruction, when large
      numbers of basal cells of the urothelium are known to incorporate 3HTdR (i.e.,
      synthesize DNA), showed labeling in most layers of the urothelium seven days
      after injection, but levels of labeling in bladders injected TwoD or ThreeD were
      lower than those injected OneD after obstruction. The smaller numbers of
      urothelial cells labeled by 3H-TdR in TwoD bladders were found in clusters where
      one or two alternate or adjacent layers of cells were labeled. Obstructed animals
      injected ThreeD after surgery showed even less labeling. This evidence clearly
      supports the hypothesis that DNA synthesis that occurs in the urothelium within
      24 h after obstruction is followed by proliferation, because by the seventh day,
      labeling can be found at all levels of the urothelium. The decline of labeling in
      TwoD and ThreeD animals suggests that the proliferative stimulus probably
      operates only during the first 24 h after insult. The data suggest that a
      substantial fraction of the urothelium enters one or more rounds of proliferation
      following obstruction and support the contention that hyperplasia does occur.

PMID- 8751165
TI  - ATP modulation of the ligand binding and signal transduction activities of the
      type C natriuretic peptide receptor guanylate cyclase.
AB  - The type C natriuretic peptide (CNP)-activated guanylate cyclase (CNP-RGC) is a
      single-chain transmembrane-spanning protein, containing both CNP binding and
      catalytic cyclase activities. Upon binding CNP to the extracellular receptor
      domain, the cytosolic catalytic domain of CNP-RGC is activated, generating the
      second messenger cyclic GMP. Obligatory in this activation process is an
      intervening signal transduction step which is regulated by ATP binding to the
      cyclase. This bridges the events of ligand binding and cyclase activation. A
      defined sequence motif (Gly499-Xa-Xa-Xa-Gly503), termed ATP regulatory module
      (ARM), is critical for this step. The present study shows that ATP not only
      amplifies the signal transduction step, it also concomitantly reduces the ligand
      binding activity of CNP-RGC. Reduction in the ligand binding activity is a
      consequence of the transformation of the high affinity receptor-form to the low
      affinity receptor-form. A single ARM residue Gly499 is critical in the mediation
      of both ATP effects, signal transduction and ligand binding activity of the
      receptor. Thus, this residue represents an ATP bimodal switch to turn the CNP
      signal on and off.

PMID- 8751166
TI  - The relationship between oxygen saturation and the clinical assessment of acutely
      wheezing infants and children.
AB  - The objective of this study was to determine the relationship between oxygen
      saturation (Sao2) and traditional clinical assessment measures in infants and
      young children presenting as outpatients with acute wheezing. To accomplish this,
      Sao2 before and after medication was compared in a post hoc analysis with the
      clinical response to treatment (respiratory rate and a standardized index of
      respiratory distress) in children who participated in a randomized, placebo
      controlled medication trial. The study was done in a pediatric emergency
      department and outpatient clinic, and the participants were 74, full-term
      previously well infants and young children, aged 1 to 36 months (mean age 16.1
      months), presenting with acute wheezing and participating in the randomized
      trial. The results showed that Sao2 was found to be inversely correlated with
      both respiratory rate (r = -0.29, P < or = 0.05) and an index of respiratory
      distress (r = -0.36, P < or = 0.01) prior to medication but not afterward. There
      was no significant difference in Sao2 when infants, who had a clinical response
      to treatment based on a priori criteria, were compared to nonresponders (mean
      difference per patient: responders = 0.86% vs nonresponders = 0.79%, P = 0.51).
      This was due to a large amount of individual variability in postmedication Sao2
      in both groups. We conclude that, before therapy, there are only weak
      correlations between SaO2 and both respiratory rate and an index of respiratory
      distress in acutely wheezing infants and children. After therapy, young children
      can appear clinically improved but measured oxygen saturation may be variable and
      not correlated with traditional clinical assessment measures.

PMID- 8751168
TI  - Lumbar puncture in the clinical evaluation of children with seizures associated
      with fever.
AB  - This study was prospectively conducted to determine the frequency and yield of
      lumbar punctures performed in children with fever and seizures and to identify
      the criteria that were used by emergency physicians in selecting patients for
      this diagnostic procedure. During the five-year period from 1988 to 1992, 200
      previously healthy children aged three months to five years were brought
      consecutively to the pediatric emergency department, after their seizure
      associated with fever. Lumbar puncture was performed in 51% of the cases and
      resulted in the detection of seven (3.5%) cases of meningitis, three (1.5%) of
      which were bacterial. An age less than 18 months, a febrile illness lasting over
      48 hours, suspicious symptoms and signs of meningitis, and complex seizure
      features had significant influence on the decision of performing a lumbar
      puncture. Most children with meningitis had lethargy, irritability, and vomiting,
      and all had complex seizure features.

PMID- 8751167
TI  - Characteristics of frequent pediatric emergency department users.
AB  - The purpose of this study was to examine the medical and demographic
      characteristics of patients who frequently seek emergency care at a pediatric
      emergency department (ED). Registration information of ED visits during the study
      period from 11/1/87 to 5/31/92 (4.6 years) was stored in a data base. Patients
      with 10 or more ED visits during this study period were considered to be
      "frequent" ED users. Outpatient and inpatient medical records of these patients
      were manually reviewed. Demographics, chronic conditions, and the acute
      conditions for each ED visit were coded and analyzed. During the study period,
      there were 79,049 ED patient visits under 21 years of age. Of the patients born
      after 1970, there were 47,451 visits by patients seen one or two times, 25,883
      visits by patients seen three to nine times, and 5178 visits by 357 patients seen
      in the ED ten times or more. Ninety-nine patients were seen more than 15 times,
      39 patients were seen more than 20 times, 17 patients were seen more than 25
      times, and 10 patients were seen more than 30 times. Two hundred sixty-five of
      the 357 frequent ED users (74%) had chronic disease conditions. Two hundred and
      twenty-three of them had good functional status, 25 had mild or moderate
      impairment in carrying out activities of daily living, and 17 had severe
      impairment of function. The most common chronic medical conditions were recurrent
      wheezing (226), neurologic conditions (33), gastrointestinal conditions (13),
      cardiac conditions (12), and endocrine conditions (9). The other 92 were assessed
      as healthy children. Patients' immunization status were up to date as of the last
      ED visit during the study period in 329 patients (92%). Pediatricians were the
      primary care providers in 339 patients (95%). Medical insurance status of
      patients follows: private insurance (38%), military (0.3%), Medicaid or state
      assistance (60%), and no insurance (1.4%). Polynesian ethnic groups were over
      represented in the cohort of frequent ED users. We conclude that cultural
      differences appeared to be an important factor associated with frequent ED use by
      healthy persons. Medical care resources as measured by immunizations, insurance,
      and identification of a primary care physician did not appear to be deficient in
      this cohort of frequent ED users. Since recurrent wheezing is a dominant chronic
      condition among frequent ED users, pediatric emergency medicine training programs
      may consider the inclusion of the chronic management of wheezing in their
      curriculum.

PMID- 8751169
TI  - Clinical effect of a quality assurance system for radiographs in a pediatric
      emergency department.
AB  - The objective of this study was to determine the clinical relevance and
      effectiveness of a quality assurance system used to identify discordant x-ray
      interpretations between emergency department pediatricians and pediatric
      radiologists in the emergency department of a large pediatric hospital. Of 5862
      patients who underwent 8174 radiographic studies during a one year period, 286
      patients with discordant radiographic diagnoses were identified. The incidence of
      discordant radiograph interpretation was determined to be 3.5% (286/8174
      studies). Of those patients with discordant diagnoses, 11.5% (33/286 discordant
      diagnoses) received immediate intervention by the emergency department, 64.0%
      (183) received subsequent intervention at their follow-up appointment or by the
      inpatient team caring for them, 9.4% (27) required no intervention, and 15.0%
      (43) had no evidence of necessary intervention documented on their medical
      record. While only 33/5862 (0.6%) patients receiving radiographs after routine
      working hours required immediate intervention by the emergency department, this
      intervention was potentially lifesaving. No adverse outcomes were identified in
      this group of patients who did not receive immediate interpretation of their
      radiographs by a radiologist. When 24-hour in-house radiology coverage is not
      provided, a quality assurance system that recalls patients identified with
      discordant radiographic diagnoses, who may require a change in management,
      appears to be an effective method of patient management only when discordant
      interpretations are identified and promptly acted upon.

PMID- 8751170
TI  - Emergency department presentation and management of pediatric heart transplant
      recipients.
AB  - The object of this study was to review and delineate the presenting complaints,
      signs, symptoms, and Emergency Department (ED) management of pediatric heart
      transplant recipients who presented to Loma Linda University Medical Center's
      (LLUMC) Emergency Department. A retrospective chart review was made of all of the
      pediatric heart transplant patients who presented to the ED at LLUMC from January
      1986 through February 1993. The department is part of a 600-bed university
      hospital with an associated 250-bed children's hospital that includes a pediatric
      heart transplant center and an ED that sees over 38,000 patients per year. The
      retrospective review collected information relating to chief complaint, physical
      findings, laboratory analysis, and diagnoses. Forty-seven patients (23%)
      presented to the ED for a total of 76 visits. The patients presented a median of
      278 days (range 19 days to 6.5 years) after transplantation. The most common
      chief complaints were related to the respiratory tract, and the most common
      diagnoses (55%) were related to infectious processes. Fever was present in 21% of
      the visits. Three of 13 blood cultures obtained were positive. Cardiac symptoms
      were present in 14% of the visits with two rejection episodes. Hospital admission
      was required for 22 (29%) of the ED visits. Results showed that pediatric heart
      transplant recipients are most likely to present to the ED with infections.
      Although infections from opportunistic organisms and bacteremia must be
      considered, most infections are similar to those in the nontransplanted child.
      Life-threatening conditions such as graft rejection are less likely.
      Nevertheless, the emergency physician should maintain caution in the evaluation
      of these patients. Close cooperation and consultation with the transplant team
      will assure the optimal outcome for these patients.

PMID- 8751171
TI  - Preferences of parents for pediatric emergency physicians' attire.
AB  - While several studies have evaluated patient/parent's preference for physicians'
      attire in pediatric clinics, pediatric wards, and in adult emergency settings,
      none has been done in a pediatric emergency department (PED). Furthermore,
      factors that may influence these preferences such as severity of illness, time of
      visit, and type of emergency department (ED) visit (surgical vs medical) have not
      been considered. This study was designed to evaluate parents' attitudes toward
      pediatric emergency department physicians' professional appearance. By way of a
      survey, the parents/guardians of 360 patients presenting to Children's Hospital
      Medical Center PED in Cincinnati, Ohio, were presented with eight photographs of
      physician pairs (male/female) dressed in different levels of attire ranging from
      a formal style (white laboratory coat, dress shoes, and tie) to surgical scrubs
      with tennis shoes. They were asked to choose the pair of practitioners they liked
      the most and the least, and to indicate whether their perception of competence
      was affected by physician attire. Preferences were analyzed by gender, age,
      responsible person, insurance group, type of visit, severity of illness, and time
      of visit. The results showed that, when asked which physicians they would prefer
      the most to evaluate their child in the PED, the majority of subjects chose
      photographs of physicians dressed most formally (158/360 [chi 2, P < 0.0001]).
      When asked which physician they preferred the least, 229 subjects chose the
      photograph of doctors wearing no white laboratory coat, no tie, and tennis shoes
      (chi 2, P < 0.0001). Neither severity of illness, time of visit, insurance group,
      age, race, or gender of the guardian or parent had a significant statistical
      effect on the most preferred or disliked attire. However, subjects visiting the
      ED between 7 AM and 11 PM clearly preferred the formal attire when compared with
      the 11 PM to 7 AM shift (chi 2, P = 0.016). A significant difference was noted
      between the preference of surgical scrubs by the parents of patients with
      surgical emergencies (42/90 [58%]) vs medical patients (30/270 [23%]) (chi 2, P <
      0.0001). Combining parents' selections, 75% preferred photographs of physicians
      wearing white laboratory coats, while 84% chose photographs of doctors who wore
      tennis shoes as the least liked physicians. Seventy-two percent of parents felt
      the physicians they preferred the most were not necessarily more capable than the
      other choices. Sixty-nine percent of subjects felt that it did not matter what
      their pediatric emergency physician was wearing. Formal attire was associated
      with "professional appearance" in 64% of the responses. Our study demonstrated
      that: 1) pediatric emergency physician's attire does not matter to most parents.
      However, when asked to choose, clear preferences for likes and dislikes become
      evident. 2) Parents/guardians prefer pediatric emergency physicians who wear
      formal attire, including white laboratory coat, and do not like casual dress with
      tennis shoes. 3) Severity of illness, insurance type, and age, race, and gender
      of guardians do not affect preferences. 4) Parents of patients with surgical
      emergencies are more likely to prefer doctors wearing surgical scrubs. 5) Parents
      visiting the ED during night shift (11 PM to 7 AM) showed less interest in formal
      attire. Our findings may assist in parent/physician interaction in a PED setting.

PMID- 8751172
TI  - Evaluation of an end-tidal CO2 detector during cardiopulmonary resuscitation in a
      canine model for pediatric cardiac arrest.
AB  - Our objective was to evaluate a colorimetric end-tidal CO2 detector in a canine
      model for pediatric cardiac arrest. In a prospective unblinded study, cardiac
      arrest was induced in 11 anesthetized and paralyzed puppies, weighing 5.0 to 6.1
      kg, by clamping the endotracheal tube (ETT) and discontinuing mechanical
      ventilation. During cardiopulmonary resuscitation (CPR), the detector and the
      capnometer were connected between the ETT and ventilator tubing. Color shades on
      the detector ranged from 1 (purple) to 6 (yellow) corresponding to increasing
      concentrations of CO2. End-tidal CO2 concentrations as indicated by detector
      color and capnometric reading were monitored and recorded throughout the study.
      The results showed that there was a significant correlation between the detector
      color score and capnometric readings (P < 0.001). A sudden rise in end-tidal CO2
      indicated by both the capnometer and the detector occurred at return of
      spontaneous circulation (ROSC) in seven or < 1 minute before ROSC in four
      animals. This association was significant (P = 0.0009). We conclude that these
      results demonstrate that, in a canine model for pediatric cardiac arrest, the
      detector readings correlate with capnometry during CPR and indicate ROSC.

PMID- 8751173
TI  - Felbamate overdose: a case report and discussion of a new antiepileptic drug.
AB  - Felbamate was approved in July 1993 for use alone or in combination with other
      antiepileptic drugs for partial seizures and Lennox-Gastaut syndrome. We report
      an overdose of felbamate in a teenage female patient who, in a suicide gesture,
      ingested eight times her maximum dose and suffered only mild side effects. This
      first report of a felbamate overdose is presented and followed by a discussion of
      felbamate's effectiveness, pharmacology, adverse effects, and drug interactions.

PMID- 8751174
TI  - Blunt urogenital trauma in prepubescent female patients: more than meets the eye!
AB  - Blunt traumatic injury to the urogenital region in the prepubescent girl is
      commonly evaluated in pediatric emergency departments (ED). The purpose of this
      study is: 1) to establish recommendations for an accurate, painless (both
      physically and psychologically), and timely diagnosis, and 2) to determine
      whether the ED examination can accurately determine the extent of the injury.
      Over a 24-month period (January 1991 through December 1992), 22 girls with blunt
      trauma to the urogenital region (mean age 5.7 years, range 2-9 years) were
      retrospectively evaluated. Initial ED evaluations were by both an emergency
      physician and a pediatric surgeon. All 22 patients underwent an examination under
      anesthesia (EUA) in the operating room to evaluate the extent of the injury and
      to repair the injury as needed. Follow-up was obtained in all patients and
      averaged 18 months. The findings at EUA demonstrated a significant disagreement
      with the preoperative ED evaluation. In only five patients was there agreement
      between the preoperative ED assessment and the findings during the EUA (24%
      concurrence). Thus, 16 patients (76%) had injuries of greater extent than was
      appreciated during the preoperative examination in the ED. Partial or complete
      disruption of the perianal sphincters occurred in six patients (27%) and was
      unrecognized preoperatively in each. Twenty-one of the 22 patients required
      suture repair of lacerations, the remaining patient did not require surgical
      therapy. Three patients had contusions or lacerations to the urethral area
      requiring repair and/or prolonged bladder catheter drainage for two to 14 days
      (average seven days). The average hospital stay was 19.3 hours. There were three
      minor wound complications following surgery: two required repeat EUA with
      suturing or cauterization, and one required no further therapy. This study
      clearly demonstrates that the ED examination, by both emergency physicians and
      pediatric surgeons, of young girls who have suffered blunt urogenital trauma
      grossly underestimates the severity of injuries when compared to the EUA in the
      operating room. EUA is safe and allows early discharge with minimal psychologic
      sequelae. Recommendations for mandatory EUA are made.

PMID- 8751175
TI  - Familial arteriovenous malformations in children.
AB  - Cerebral arteriovenous malformations are uncommon in children. Familial incidence
      of these lesions is reported in only 10 families. We report a family in which the
      two youngest siblings had this anomaly, and we review the literature. These cases
      represent a clinical situation that emergency physicians may encounter.

PMID- 8751176
TI  - Necrobacillosis: an unusual cause of purulent otitis media and sepsis.
AB  - Necrobacillosis is a rare systemic illness caused by the anaerobic gram-negative
      bacterium, Fusobacterium necrophorum. We describe a case of necrobacillosis in a
      previously healthy child who developed purulent otitis media with sepsis caused
      by F. necrophorum. This case demonstrates that not all cases of purulent ear
      drainage are caused by the usual otopathic organisms and emphasizes the
      importance of culturing ear discharge in a child with an unusual presentation.

PMID- 8751177
TI  - Pediatric emergency medicine fellow clinical work requirements.
AB  - A wide range of clinical requirements exists among PEM fellowship programs.
      Programs are equally split concerning the question of whether fellows should work
      with supervision or independently in the first year; a significant number of
      fellowship programs require continued supervision of fellows in subsequent years.
      Orientation for first year fellows and requirements for completion of PALS,
      advanced pediatric life support (APLS), ACLS, or ATLS courses prior to their
      first independent shift varied greatly. In particular, a minority of programs
      required ATLS completion even though a majority of overall fellowship programs
      operate in a hospital designated as a Level 1 Trauma Center. Programs in which
      first-year fellows worked independently had fewer attendings and were less likely
      to provide 24-hour coverage. Fellows appear to work a similar or less demanding
      schedule than PEM attendings in most fellowship programs, and most fellowship
      directors feel that their fellows should continue with their current schedule.

PMID- 8751178
TI  - The least expensive diagnostic tool.

PMID- 8751179
TI  - Syringe infusion pumps.

PMID- 8751180
TI  - Pediatric emergency medicine: legal briefs.

PMID- 8751181
TI  - Cough and drooling for two days.

PMID- 8751182
TI  - Efficacy of oral ketamine for providing sedation and analgesia to children
      requiring laceration repair.

PMID- 8751183
TI  - [Classification of primary headache and International Headache Society diagnostic
      criteria 1988: critical review].
AB  - Following a short analysis of leading principles of the classification and
      diagnostic criteria of headaches of the International Headache Society (IHS) and
      a brief description of its nosography of primary headaches, some still debated
      issues are discussed. The IHS classification shows a good inter-observer
      reliability both at one- and two-digit levels, even though validation studies are
      lacking. On the basis of researches carried out in recent years on the evolution
      of cluster headache, on chronic daily headache, on a possible third diagnostic
      level of migraine without aura, and on the painful phase of migraine with aura,
      some proposals of revision of the IHS classification are suggested.

PMID- 8751184
TI  - Causes and mechanisms of primary headaches: toward a bio-behavioral model.
AB  - Pathophysiological mechanisms of primary headache remain obscure, despite of
      numerous hypotheses that have been postulated for either migraine and cluster
      headache. Human experimental models are not available, however, observation of
      clinical features of migraine or cluster headache attacks support animal studies
      documenting the development of neurogenic inflammation in tissues receiving
      trigeminal innervation. The latter studies provided also the background for
      better understanding the mechanism of action of aborting drugs such as
      sumatriptan and dihydroergotamine. The debate is whether the primary cause of
      migraine and other neurovascular headaches is central or peripheral in origin.
      Trigger factors (stressful events) and personality traits in migraine patients
      suggest that activation of neurovascular systems is secondary to more complex
      events taking place in the central nervous system.

PMID- 8751185
TI  - Symptomatic headaches.
AB  - This paper is aimed to discuss some aspects of so-called symptomatic or secondary
      headaches with particular reference to the diagnostic criteria proposed by the
      IHS Classification Committee on headache disorders, cranial neuralgias and other
      head pain. Symptomatic headaches, in fact, represent an heterogenous group of
      conditions, sometimes with relevant clinical importance as warning symptoms of
      major intracranial pathology, sometimes benign in nature and with ill-defined
      clinical pictures and unclear relationship with the causative factor or event. It
      is therefore important to establish general principles for a more systematic
      approach to the problem of this group of headaches, also considering that some
      particular forms of secondary headaches, may be viewed as reliable "in-vivo"
      models for pathophysiological investigation in head pain.

PMID- 8751186
TI  - [Therapeutic guidelines for headache].
AB  - Guidelines have been recently introduced in clinical practice in order to improve
      the quality of patient care reducing health-care costs. In 1993 the Italian
      Headache Society has published the "Guidelines and recommendation for the
      treatment of migraine" based on a wide revision of the existing literature and a
      consensus conference of Italian headache experts. These guidelines include the
      information necessary to make a correct diagnosis and to identify the best
      symptomatic and/or prophylactic migraine treatment. Until now guidelines for the
      treatment of tension-type headache and cluster headache are not available.
      However we can refer to the "Treatment recommendations" proposed by the
      Educational Committee of the International Headache Society. These suggestions
      indicate common practice and give precise information about types and dosages of
      the drugs utilizable for the prophylaxis and for the treatment of attacks.

PMID- 8751187
TI  - [Centro-peripheral etiopathogenesis of primary headache triggered nasally].
AB  - The presence of endonasal pathological conditions or headache accompanying
      symptoms involving the nose, show a bi-directional link between the latter and
      endocranial structures. Instrumental diagnostic procedures allow demonstration of
      anatomical variants of the bone. Frequently, surgical procedures addressed to
      correct such variants seem to resolve both headache and breathing disturbances.
      However, hyperactivity of nasal mucosa and microcirculation might be responsible
      for cephalic disturbance as a consequence of activation of neuro-vascular systems
      (trigeminal, sympathetic, parasympathetic) and explain both pain and attendant
      accompanying symptoms during migraine and cluster headache attacks. Peripheral
      triggering or aggravating factors may, therefore, be responsible for or, at
      least, contribute to pathophysiological mechanisms of certain headaches.

PMID- 8751188
TI  - [Trigemino-vegetative physiopathology in the central dysnociceptive biorhythms in
      primary headache].
AB  - The Headache is a common symptom: 80% of the population suffers from headache at
      least one time per year. This work is a review of new theories on neurovascular
      pathophysiology of primary headaches in a particular manner on rhinogenic
      headache. Besides, the authors report the results of a study carried out in 2262
      children, who where attending the primary school, in order to investigate the
      relation between allergic rhinitis and headache in children. The present study
      suggests that the headache in allergic patients is related to nasal dysfunction
      always present in these cases.

PMID- 8751189
TI  - Pathogenesis and surgical treatment of neurovascular primary headaches.
AB  - The "neurovascular primary headaches" are syndromes also pertinent to
      otorhinolaringology when CT demonstrates a reduced volume of the
      "ethmoidosphenoidal subcribriform chamber" according to the endo-exocranial
      hemoangiokinetics of this area. It is emphasized that in drug-resistant headaches
      recovery or consistent definitive improvement can be achieved only after surgical
      correction of certain anatomical parameters (P. Bonaccorsi, V.J. Novak, S.
      Hoover). Bonaccorsi and Novak independently identified the actual
      pathophysiologic mechanism and trigger zone ("dysmorphism") for various types of
      neurovascular primary headaches. Patients (n = 446) with various types of
      headaches (migraine, cluster headache and so-called idiopathic or primary
      headaches) were operated upon between 1973 and 1994. Septal correction, resection
      of the middle and superior concha, ethmoidectomy, and sphenoidectomy on the
      corresponding headache side or occasionally on both sides were carried out. Most
      patients (356, 80%) were asymptomatic postoperatively, 45 (10%) had a sensation
      of pressure in the head on rare occasions but no further migraine, and 45 (10%)
      continued to experience headache that occurred only rarely and was mild and of
      short duration. The overall success rate was 90%. For cluster headache in 20
      patients, we observed the following postoperative results: 19 cured (98%), 1
      improved (2%).

PMID- 8751190
TI  - [Primary headache and orthognathorhinodontia in childhood].
AB  - The aim of the research was to study the interrelationship between the primary
      neurovascular headaches, the various levels dimension of nasal pyramid and the
      rapid palatal expansion. Twenty-five patients, of both sexes and on developmental
      age, were studied before and after the rapid palatal expansion. All patients
      showed palatal hypoplasia and were suffering from primary neurovascular headache.
      The research was based on the cephalometric and rhinomanometric data. The
      radiographic documentation of each patient consisted of three postero-anterior
      teleradiographic projection; the first before application of the disjunction
      device, the second immediately after disjunction and the third at the end of the
      contention period. The rhinomanometric evaluation studied the reduction of nasal
      resistance values before and after palatal expansion. In all patients a constant
      increase in the values relating both skeletal and dental structures was observed.
      The nasal septum, if deviated, appeared straightend. The nasal resistances were
      decreased. The concomitant headache symptomatology presented resolution or
      recovery in the 98% of treated patients. The results should confirm the
      hypothesis of the central-peripheral theory of "primary headaches" and the
      possibility to treat the primary headaches by rapid palatal disjunction in
      eliminating the stenosis at various levels of nasal pyramid.

PMID- 8751191
TI  - [Decompressive neurovascular nose and skull-base surgery in primary headache with
      a rhinogenic trigger].
AB  - The therapeutical results such as recoveries or substantial improvements obtained
      by neurovascular decompressive functional morpho-corrective rhino-skull base
      surgery on 2124 cases of primary headaches (migraine with aura, migraine without
      aura, cluster headache, chronic paroxysmal hemicrania, tension-type headache)
      obliges a thorough review of the classical chapter on "rhinogenous headaches"
      (Bonaccorsi, Novak, Blondiau, Bisschop, Hoover, Clerico). In fact all those
      headaches seemingly "primary", but having a "central-peripheral" etiopathogenesis
      proved by a well documented (CT) volumetric reduction of "ethmoidosphenoidal
      subcribriform chamber" according to hemoangiokinetics purposes of endo-exocranial
      anastomotic circulation of this area, should be included in the chapter of
      "rhinogenous headaches". This endo-exocranial anastomotic circulation is
      considered a "functional unit" owing to the continuity of rhino-ophthalmic
      encephalic trigeminal-vegetative and vascular circuits (Hannerz, Hardebo,
      Moskowitz). These morphological abnormalities of the rhino-skull base osteo
      vascular-mucous structures acquire physio-pathological significance only in
      patients with "low pain threshold and elevated central integrative capability",
      modulated and timed by the neurogenic biorhythms. It is described the surgery of
      rhino-skull base by "neurovascular decompressive septo-ethmoidosphenoidectomy"
      procedure, either conservative or radical till the III grade monolateral with
      trigeminal and vegetative selective neurotomy that permits to save olfaction and
      to remove even the controlateral pain decompressing the circulation and
      eliminating stasis even on the opposite side. Further, it is emphasized that the
      neurological deficit or central irritative symptomatology (visual aura, sensory
      motor paresis, epilepsy) disappears after surgical removal of the "peripheral
      rhinogenous trigger". It demonstrates a cause and effect relationship that is the
      central peripheral functional interdependence, even if it's included in the neuro
      transmissive, biochemical, neuro-endocrine, constitutional background which is
      controlled by the psychical, vegetative and dysnociceptive biorhythms.

PMID- 8751192
TI  - Argyrophilic nucleolar organizer regions (AgNOR) of resected intrahepatic
      cholangiocellular carcinomas.
AB  - BACKGROUND/AIMS: Thxe argyrophilic nucleolar organized resion (AgNOR) is loop DNA
      encoded for rRNA production on the nucleoli, which controls cell proliferation
      and protein synthesis (1,2). Based on numerous studies, it has been suggested
      that the AgNOR number correlates with both cellular kinetics and the malignant
      grade of the tumor. MATERIALS AND METHODS: The argyrophilic nucleolar organized
      regions (AgNOR) of 14 operated cases with intrahepatic cholangiocellular
      carcinoma (IHCCC) were examined. RESULTS: The number of AgNOR per nucleus (the
      AgNOR score) was found to be related to both the level of carcinoembryonic
      antigen (CEA) (r = 0.63, P = 0.016) and the size of the tumor (r = 0.62, P =
      0.017). Regarding the age, sex, the presence or absence of lymph node metastasis,
      the grade of TNM classification, and the main location of the tumor, no
      statistical significance was recognized. On the other hand, both histological
      difference and differentiation were observed to remarkably reflect the AgNOR
      score (P = 0.03). The cancer-free survival and survival rate showed no
      relationship to the AgNOR score, but patients with an AgNOR number lower than 2.0
      showed a poorer cancer-free survival rate as well as a poorer survival rate. Two
      patients with a long survival, who have been free from cancer for more than 5
      years, showed a low AgNOR score (1.6, 1.7). CONCLUSIONS: The AgNOR method is
      simple, low-cost and can easily be applied to paraffin-embedded sections.
      Therefore, this score is considered to be useful in identifiying malignant
      potentiality in intrahepatic cholangiocellular carcinoma.

PMID- 8751193
TI  - The low positive rate of serum alpha-fetoprotein levels in hepatitis C virus
      antibody-positive patients with hepatocellular carcinoma.
AB  - We analyzed the clinicopathological factors influencing the serum AFP levels at
      the time of diagnosis in 114 patients with resected HCC. The proportion of HCC
      patients with high serum AFP levels (> 100 ng/ml) has been steadily decreasing
      from a rate of 57.2% in 1980 to 33.3% in 1993. A significant relationship was
      noted between the serum AFP levels and the virus marker (p < 0.01) based on a
      multivariate analysis. The proportion of HCC patients with high serum AFP levels
      was significantly less in anti-HCV- positive HCC patients than in HBsAg-positive
      HCC patients (p < 0.01). The proportion of HBsAg-positive HCC patients has been
      steadily decreasing from a rate of 48% in 1980 to 15% in 1993. In contrast, the
      proportion of anti-HCV-positive HCC patients was 69% in 1993. It is thus assumed
      that the prevalence of anti-HCV-positive HCC patients is increasing recently,
      based on the fact that the incidence of HCC patients with high serum AFP levels
      is decreasing.

PMID- 8751194
TI  - A refined method of trans-thoracoabdominal hepatectomy for cirrhotic patients
      with hepatocellular carcinoma.
AB  - A hepatectomy in cirrhotic patients with hepatocellular carcinoma, located in
      either the posterior or superior part of the right lobe, inevitably requires a
      forced mobilization of the right lobe. Such a forced procedure causes a decreased
      hepatic blood flow resulting in postoperative morbidity and mortality, as well as
      an increased risk of the intrahepatic dissemination of cancer cells during the
      operation. We have thus refined the method of trans-thoracoabdominal hepatectomy
      to minimize those demerits of conventional transabdominal hepatectomies. The main
      characteristics of our refinements are as follows; (1) an optimal incision for
      the best short-cut to the hepatocellular carcinoma is determined by a three
      dimensional imaging of either helical computed tomography and/or magnetic
      resonance imaging before operation; (2) a complete view of the operative field is
      obtained by the pertinent use of rotating the operation table, on which the
      patient is placed in a left semi-lateral position; (3) this method is suitable
      for resecting a tumor located in the posterior segment such as a posterior
      segmentectomy. This refined method is considered to decrease the postoperative
      morbidity including post-operative hepatic dysfunction and is also useful for
      cirrhotic patients with hepatocellular carcinoma.

PMID- 8751195
TI  - A quick and simple technique for selective control of hepatic arterial bleeding.
AB  - A quick and simple technique for the selective control of hepatic arterial inflow
      is described for hepatic resections or hepatic hilar lymph node dissection which
      allows arterial hemostasis without causing splanchnic congestion.

PMID- 8751196
TI  - Morbidity and mortality after hepatic resection in the modern era.
AB  - BACKGROUND/AIMS: The purpose of this study was to clarify the risk factors
      associated with complications following hepatic resections and discuss the
      appropriate types of perioperative management. MATERIALS AND METHODS: A
      retrospective analysis was made of the complications in 355 patients undergoing
      hepatic resection between April 1985 and August 1992 at the Second Department of
      Surgery, Kyushu University Hospital. The patients were placed in two groups
      according to the occurrence of complications: patients with morbidity and/or
      mortality (187 patients); patients without either morbidity or mortality (168
      patients). RESULTS: The leading complications were the accumulation of fluid in
      the abdominal and pleural cavities along with septic complications. The only
      significant factory affecting morbidity and mortality among the preoperative
      medical conditions was the presence of diabetes while, in addition, the patients
      with morbidity and/or mortality had higher levels of perioperative transaminase
      and serum creatinine as compared with those in patients without either morbidity
      or mortality. CONCLUSIONS: The perioperative strategies for reducing morbidity
      include the strict control of diabetes to reduce septic complications as well as
      preserve renal function, which can protect against the refractory accumulation of
      fluid in the peritoneal and pleural cavities.

PMID- 8751197
TI  - Surgical results of spontaneously ruptured hepatocellular carcinoma.
AB  - Seventeen patients with ruptured hepatocellular carcinoma (HCC) underwent a
      hepatic resection from 1985 to 1992 at either Kyushu University Hospital or
      Iizuka Hospital in Japan. They all underwent elective surgical procedures except
      for one patient who experienced a repeated rupture during hospitalization. A
      comparative study between the patients with ruptured HCC and non-ruptured large
      HCC measuring more than 6 cm in size (n = 29) revealed that the 3-year disease
      free survival rate of the ruptured HCC group was 14.5% which was worse than that
      of the non-ruptured group at 39.9%. There was no difference in the rates of
      peritoneal dissemination, distant metastasis or intrahepatic recurrence between
      the two groups. Regarding the intrahepatic recurrence pattern, widespread
      multinodular recurrence frequently occured in the ruptured patients, which was
      thought to be caused by the high incidence of venous invasion in the primary
      tumor. The intratumor pressure of the ruptured HCC appeared to be elevated and is
      considered to be one of the main reasons for the high incidence of venous
      invasion.

PMID- 8751198
TI  - Influence of blood transfusion on postoperative long-term liver function in
      patients with hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: To research for possible adverse effects of blood transfusion on
      liver function at a relatively long term after hepatic resection, liver function
      tests at one and two years after the surgery were studied in patients with
      hepatocellular carcinoma. MATERIALS AND METHODS: Seventy-one patients with no
      evidence of cancer recurrence during two years after the surgery were selected
      for this retrospective analysis. Patients were divided into two groups depending
      on perioperative blood transfusion: those who received blood transfusion (BT(+),
      n = 38), and those without blood transfusion (BT(-), n = 33). RESULTS: There were
      no statistical difference in the preoperative clinical features including liver
      function tests except decreased prothrombin time index (P < 0.01) and larger
      amount of intraoperative blood loss (P < 0.01) in BT(+) group. Platelet counts at
      2 year after the surgery were significantly higher in the BT(-) group (P < 0.05).
      Two-way ANOVA showed no significant difference in liver function tests between
      the two groups. In multiple regression analysis, blood transfusion significantly
      correlated with serum total bilirubin at 1 year, but did not at 2 years after the
      surgery. CONCLUSIONS: The influence of blood transfusion in the patients with
      hepatocellular carcinoma was considered to be minimum within 2 years after
      hepatectomy.

PMID- 8751199
TI  - Early recurrence after surgery of hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: In 231 patients with hepatocellular carcinoma who underwent
      liver resection from 1986 to 1992 to determine the significance of alpha
      fetoprotein (AFP) levels. MATERIALS AND METHODS: There were 13 patients (5.6 per
      cent) with early recurrence within six months after hepatectomy. RESULTS:
      Preoperative serum alpha-fetoprotein (AFP) levels were significantly higher in
      patients with early recurrence (p < 0.01). Postoperative histological examination
      revealed that there were significant correlations between patients with early
      recurrence and intrahepatic metastasis (p < 0.01), and portal vein infiltration
      (p < 0.01). There were significant correlations between patients with early
      recurrence and preoperative diagnosis of intrahepatic metastasis (p < 0.01),
      however, preoperative diagnosis of portal vein infiltration could not be detected
      enough. Eight (73%) of 11 patients with over 1000 ng/ml of AFP and preoperative
      diagnosis of intrahepatic metastasis had early recurrence (p < 0.01).
      CONCLUSIONS: We found that patients of hepatocellular carcinoma with over 1000
      ng/ml of AFP and preoperative diagnosis of intrahepatic metastasis are the most
      important factors in the preoperative clinical data linked to early recurrence
      type of HCC after hepatectomy.

PMID- 8751200
TI  - Amebic liver abscess "a 5 year Mexican experience with a multimodality approach".
AB  - BACKGROUND/AIMS: Amebic liver abscess is a frequent problem in Mexico. The
      morbidity and mortality is reported to be high in different series. The aim of
      this study was to evaluate the morbidity and mortality of ALA in our center and
      evaluate our current management used. MATERIALS AND METHODS: Fifty patients were
      included in our study. Thirty-four (68%) were males, 16 (22%) were females. The
      age range was between 22 and 83 years (mean 50 years). The majority presented
      abdominal pain (95%), fever (82%) and hepatomegaly (72%). leukocytosis was
      observed in 72%, hypoalbuminaemia in 62%, thrombocytosis in 42%. The seroemeba
      reaction was positive in 90%. The diagnostic methods used were ultrasound in 42,
      computed tomography in 20 and isotope scan in 12. RESULTS: Medical treatment
      alone was used in 24 patients, 15 required percutaneous drainage and 11 surgery.
      Fifteen patients (38%) presented medical complications. The hospital stay raged
      between 5 and 44 days (mean 15 days). One patient died in a median follow up of
      31.4 months. Multimodality management was liberally used in our patients.
      Amebicidal drugs were used initially and controlled the disease in 24 patients,
      15 patients required percutaneous drainage because of lack of control of the
      disease or risk of complications and 11 patients required surgery to treat
      complications. CONCLUSION: With these approaches the morbidity and mortality of
      ALA in our center has remained low.

PMID- 8751201
TI  - A clinicopathologic study of primary cholesterol hepatolithiasis.
AB  - BACKGROUND/AIMS: We conducted the present study in order to clarify the
      clinicopathologic features of primary cholesterol hepatolithiasis and compare
      them with those in primary calcium bilirubinate hepatolithiasis. MATERIALS AND
      METHODS: We reviewed the clinicopathologic features of 24 patients with primary
      cholesterol hepatolithiasis. The clinical symptoms were mild, and the median
      duration of symptoms was 5 years. RESULTS: In 22 patients complete stone
      clearance was obtained using percutaneous cholangioscopic lithotomy, partial
      hepatectomy, or their combination. The patients showed excellent clinical outcome
      (median follow-up period, 6 years) despite the absence of bilioenteric drainage.
      Stones have recurred in 4 patients, who remain asymptomatic. The histopathologic
      findings in 7 hepatectomized patients were compared with those in 7 patents with
      calcium bilirubinate hepatolithiasis. The inflammatory changes around the stone
      containing duct, i.e., wall thickening, fibrosis, sludge formation, and glandular
      hyperplasia, were significantly milder in the cholesterol hepatolithiasis
      patients (p < 0.01 or p < 0.05). CONCLUSIONS: These clinical and histopathologic
      findings indicate that primary cholesterol hepatolithiasis should be regarded as
      a different clinical entity from calcium bilirubinate hepatolithiasis which has a
      close relationship with bile stasis and bacterial infection as etiological
      factors.

PMID- 8751202
TI  - Zinc absorption and its correlation with results of oral zinc tolerance testing
      in nonalcoholic liver cirrhosis; kinetic study.
AB  - BACKGROUND/AIMS: Liver cirrhosis is often complicated by symptoms of zinc
      deficiency, i.e., disturbances of taste and smell, skin eruptions, and other
      symptoms. We evaluated zinc absorption in patients with nonalcoholic liver
      cirrhosis to clarify the cause of zinc deficiency. METHODS AND MATERIALS: The
      absorption of zinc was calculated from the results of both the oral and
      intravenous zinc loading tests. RESULTS: Absorption was significantly reduced the
      cirrhotic patients, 20.4 +/- 10.7% as compared with the controls, 38.3 +/- 11.0%.
      In the cirrhotic patients with hepatocellular carcinoma, it was 17.8 +/- 9.3%,
      not significantly different from that of cirrhotics without hepatocellular
      carcinoma, 24.1 +/- 10.7%. CONCLUSIONS: Therefore, the development of
      hepatocellular carcinoma in patients with nonalcoholic liver cirrhosis had no
      influence on zinc absorption. Because a lower correlation between zinc absorption
      and the results of oral zinc tolerance testing was observed, the oral zinc
      tolerance test alone cannot be used as an accurate procedure for evaluating zinc
      absorption in liver cirrhosis. One should thus use both the intravenous as well
      as the oral zinc loading test when evaluating zinc absorption.

PMID- 8751203
TI  - Radiofrequency hyperthermia for malignant liver tumors: the clinical results of
      seven patients.
AB  - BACKGROUND/AIMS: Since 1991, we have performed radiofrequency hyperthermia
      combined with chemotherapy preliminarily for malignant liver tumors. MATERIALS
      AND METHODS: We were using the BSD-1000 Annular phased array system and monitored
      intratumoral, skin superficial and intrarectal temperature. The subjects
      consisted of five patients with hepatocellular carcinoma and two with metastatic
      liver cancer. All seven patients received therapy from once to five times, with a
      mean frequency of 3.3 +/- 1.3 (S.D) times. RESULTS: The maximum intratumoral
      temperature was 42.2 +/- 1.0 (S.D.) degrees of centigrade, the length that
      intratumoral temperature reached 41 degrees of centigrade was 17.1 +/- 6.9 (S.D.)
      minutes and the length that intratumoral temperature kept above 41 degrees of
      centigrade was 30.8 +/- 7.5 (S.D.) minutes. The skin superficial and intrarectal
      temperature were 39.3 +/- 1.1 (S.D.) degrees of centigrade, 40.3 +/- 1.8 (S.D.)
      degrees of centigrade, respectively. The most common complaints were nausea (28%)
      and dyspnea (14%). CONCLUSIONS: No severe side effects were observed, although
      one case experienced an abdominal skin burn. We thus found that it was possible
      to heat deepseated liver tumors safely.

PMID- 8751204
TI  - A case of intrahepatic stones with an anomalous intrahepatic portal venous
      system.
AB  - A 64-year-old woman who had undergone surgery for gallstones twice was admitted
      with epigastric pain and fever. Ultrasonography revealed gallstones in the
      dilated left lateral intrahepatic bile ducts. Abdominal computed tomography
      disclosed atrophy of the left lateral segment and the right lobe of the liver,
      and hypertrophy of the left medial segment and the caudate lobe. Percutaneous
      transhepatic cholangiography demonstrated that the stones were localized in the
      left lateral intrahepatic bile ducts, and that the choledochoduodenostomy
      previously established was patent. Percutaneous transhepatic portography revealed
      that the left portal vein was absent and the left medial segment was supplied by
      the right portal vein. Left lateral hepatic segmentectomy and release of the
      choledochoduodenostomy were performed. Postoperative recovery was good, and the
      patient is now well without any complaint. This report discusses the surgical
      treatment for intrahepatic stones under very complicated conditions and the
      relationship between intrahepatic stones and anomalous portal venous system.

PMID- 8751205
TI  - Case of bile duct carcinoma of the hepatic hilus with segmental obstructive
      cholangitis.
AB  - Cholangitis is a risk factor for posthepatectomy liver failure and therefore
      should be treated aggressively by urgent biliary drainage before definitive liver
      surgery for bile duct carcinoma. We present a case of bile duct carcinoma of the
      hepatic hilus with segmental cholangitis. The patient was a 38-year-old man.
      Percutaneous transhepatic biliary drainage (PTBD) was performed in the left
      anterior, right anterior, and right posterior segmental ducts to alleviate
      jaundice and to evaluate the biliary system. One month after PTBD, the patient
      developed high fever with leukocytosis, suggesting the onset of segmental
      cholangitis. An urgent repeat PTBD was carried out at the caudate and left medial
      segmental bile ducts. The bile juice was purulent, and the tube cholangiogram
      revealed miliary abscesses. After PTBD, cholangitis was subsided, and extended
      left hepatic lobectomy with caudate lobectomy was performed. The postoperative
      recovery was uneventful and the patient has been well for 13 months. We conclude
      that the onset of fever in patients with hilar bile duct cancer, PTBD catheters,
      and undrained biliary segments suggests the presence of segmental cholangitis.

PMID- 8751206
TI  - Intrahepatic cholangiocarcinoma with a long-term survival of 12 years after
      surgical resection: report of a case and review of the literature.
AB  - The prognosis of primary liver cancer, especially cholangiocarcinoma, is
      extremely poor. A long term, 12 years survivor of intrahepatic cholangiocarcinoma
      arising in a local dilatation of the intrahepatic bile duct is presented. A 40
      year-old male patient was presented with recurrent upper abdominal pain, fever,
      and jaundice. Computed tomography revealed a localized duct dilatation, and
      ultrasound clearly demonstrated a tumor mass arising within the bile duct. At
      surgery in March, 1982, the tumor mass was resected and histologically confirmed
      as a well differentiated papillary adenocarcinoma arising. In March, 1994, the
      patient is alive and cancer-free, 12 years after surgical resection. To our
      knowledge, there has been no report on a patient surviving more than 10 years
      after initial treatment. This case suggests that a localized cystic dilatation of
      the intrahepatic-bile duct on imaging modalities may harbor a bile duct
      carcinoma, and this in turn may contribute to early diagnosis of carcinomas and
      improved long term survival.

PMID- 8751207
TI  - Multiple angiomyolipomas of the liver (case report).
AB  - Angiomyolipoma of the liver is an extremely rare type of tumor and reported cases
      are few and far between. This case study reports on a 37-year-old woman who
      suffered from multiple angiomyolipomas of the liver. Ultrasonography (US) and
      computed tomography (CT) initially revealed the existence of two tumors located
      in the right lobe of the liver and measuring 20 x 15 mm and 8 x 7 mm in size. The
      patient underwent partial resections of the liver. Histopathologic examination of
      both the resected specimens revealed angiomyolipoma. This is the first reported
      case of multiple angiomyolipomas of the liver. Furthermore, the lesions of our
      case study were small in size and rich in fat component. Under such conditions,
      preoperative examination resulting in an angiomyolipoma diagnosis is difficult
      even with the aid of imaging modality and needle biopsy techniques.

PMID- 8751208
TI  - Serial measurement of serum C-reactive protein facilitates evaluation in
      alcoholic hepatitis.
AB  - BACKGROUND/AIMS: An ability to measure inflammatory activity in alcoholic
      hepatitis is desirable for assessing its natural history and therapeutic
      responses, but convenient and simple parameters are lacking. To determine whether
      acute phase proteins could be useful for this purpose, we studied serum CRP and
      several other acute phase proteins in a series of patients with alcoholic
      hepatitis. MATERIALS AND METHODS: We examined sequential sera from 72 patients
      with serum bilirubin greater than 5 mg/dl. RESULTS: The short-term mortality
      during the approximately 30 day study period was 18%. There was moderate to
      marked elevation of serum c-reactive protein at initial testing in all patients
      with alcoholic hepatitis. In consecutive sera within the first week of testing, a
      further rise in c-reactive protein was noted significantly more frequently among
      patients that did not survive subsequently. Serum c-reactive protein levels
      gradually declined in recovering patients but were still abnormal at the end of
      the study period. In contrast, serum haptoglobin levels were subnormal initially,
      as well as throughout the subsequent short-term course. Among other acute phase
      proteins, serum ceruloplasmin, transferrin, a-1 acid glycoprotein and a-2
      macroglobulin remained in the normal range. CONCLUSIONS: These results suggest
      that the expression of c-reactive protein but not haptoglobin is upregulated in
      alcohol-induced acute liver injury. Serial measurements of serum c-reactive
      protein should be useful in assessing the clinical activity of alcoholic
      hepatitis.

PMID- 8751209
TI  - Serum hyaluronate predicts response to interferon-alpha therapy in patients with
      chronic hepatitis C.
AB  - BACKGROUND/AIMS: The response to interferon therapy for chronic hepatitis is
      known to decrease with progression of the hepatic fibrosis. On the other hand,
      serum hyaluronate reflects hepatic sinusoidal capillarization or liver cirrhosis,
      and also serum type IV collagen, which is one of the main components of the
      basement membrane, rises with the progression of hepatic fibrosis. In this study,
      the relationship between the degree of hepatic fibrosis and the response to
      interferon-alpha was determined retrospectively in patients with chronic
      hepatitis C. In addition, whether the measurement of serum hyaluronate and type
      IV collagen before interferon-alpha therapy was useful for predicting the
      response to interferon-alpha therapy in chronic hepatitis C was determined.
      MATERIALS AND METHODS: Thirty-seven patients with elevated serum ALT levels for
      at least 6 months and histologically determined chronic hepatitis were studied.
      All patients were positive for anti-HCV and negative for hepatitis B surface
      antigen. Twenty-eight healthy adults with normal blood biochemical data, who were
      negative for hepatitis B antigen and HCV antibody tests, had limited alcohol
      intake were used as controls. The test group was given IFN-alpha by intramuscular
      injection for 14 days, and then were treated 3 times per week for 24 weeks.
      RESULTS: The extent of hepatic fibrosis, particularly, perisinusoidal fibrosis (P
      < 0.01) was significantly greater in nonresponders than in responders. The mean
      serum hyaluronate and type IV collagen levels were more elevated in nonresponders
      than in responders, especially, the serum hyaluronate level showed a significant
      difference (P < 0.01). Most of the patients having a serum hyaluronate level of
      more than 100 ng/ml were nonresponders who had chronic active hepatitis with
      bridging necrosis on liver biopsy. Serum hyaluronate and type IV collagen levels
      showed significant positive correlation with degree of the portal fibrosis (P <
      0.01), perisinusoidal fibrosis (P < 0.001) and focal necrosis (P < 0.01) in
      histological findings of liver biopsy specimens. CONCLUSION: These results
      suggest that serum hyaluronate and type IV collagen levels reflect the extent of
      the hepatic fibrosis in chronic hepatitis C and also that serum hyaluronate level
      predicts the response to interferon-alpha therapy in patients with chronic
      hepatitis C.

PMID- 8751210
TI  - Treatment of chronic hepatitis C with interferon-alpha in patients infected with
      the human immunodeficiency virus.
AB  - BACKGROUND/AIMS: The incidence of hepatitis C infection is increased in subjects
      with human immunodeficiency virus infection, although the relative frequency of
      hepatitis b infection is higher than that hepatitis c. The present study assessed
      the effect of IFN-a on chronic hepatitis C in HIV infected patients. MATERIAL AND
      METHODS: Twenty patients with chronic hepatitis C, nine positive for antibodies
      to the human immunodeficiency virus and eleven HIV-seronegative, were treated
      with interferon a-2b. RESULTS: Five HIV-positive patients responded to therapy
      with a complete (three) or partial (two) remission of hepatitis at the end of
      treatment. A sustained response was achieved in four patients. From the HIV
      negative patients eight responded with a complete (six) or partial (two)
      remission. The response was sustained in six patients. Hepatitis C virus-RNA
      became at least temporarily undetectable in three HIV-positive and six HIV
      negative patients. No severe toxicity of interferon treatment was seen in either
      the HIV-positive or the HIV-negative patients. CONCLUSION: The present results
      indicate that interferon treatment of chronic hepatitis C in HIV-positive
      patients is successful in a considerable number of individuals. However it might
      be inferior to the results in HIV-negative patients.

PMID- 8751211
TI  - Predictive factors for efficacy of interferon therapy in chronic hepatitis type
      C.
AB  - BACKGROUND/AIMS: It has recently become possible to quantify HCV-RNA in serum and
      to analyze the HCV-RNA genotype. In this study, we investigated the relationship
      among the response to interferon therapy, the HCV-RNA concentration, genotype and
      histological findings of the liver. PATIENTS AND METHODS: Sixty-three patients
      with chronic hepatitis type C received interferon alfa therapy for 24 weeks. The
      HCV-RNA concentration in serum was measured semiquantitatively with reverse
      transcript semi-nested polymerase chain reaction and classified as negative to
      +3. HCV-RNA genotype was analyzed using a mixture of four type specific primers.
      RESULTS: HCV-RNA concentration was significantly higher in patients with genotype
      II and CAH2B than genotype III, CPH and CAH2A (p < 0.05). At 24 weeks after the
      end of interferon therapy, HCV-RNA in serum disappeared in 24 of 63 patients
      (38%). Strong resistance to the therapy was noted in patients with both genotype
      II and a high concentration of HCV-RNA in serum (the efficacy was only 7%).
      Therapy efficacy decreased with the severity of liver histological findings,
      reaching only 20% in those with CAH2B. CONCLUSION: Both the concentration and
      genotype of HCV-RNA seem to be important factors in determining the efficacy of
      interferon therapy.

PMID- 8751212
TI  - The predictive value of serum laminin for the risk of variceal bleeding related
      to portal pressure levels.
AB  - BACKGROUND/AIMS: This paper presents the results of the radioimmunologic
      determination of laminin in serum of patients with alcoholic liver cirrhosis with
      a preserved hepatic function, trying to evaluate its predictive value for the
      risk of variceal bleeding, assessed by a portal pressure level equal to or higher
      than 12 mmHg. PATIENTS AND METHODS: Twenty alcoholic cirrhotic patients with a
      preserved hepatic function as assessed by the Child-Pugh classification, had
      their peripheral blood taken for radioimmunological determination of serum
      laminin and were submitted to hepatic vein catheterization for portal pressure
      measurement. RESULTS: A positive and significant correlation (r = 0.70, p <
      0.001) was found between serum laminin levels (mean value + SD = 2.70 + 1.13
      U/ml) and hepatic vein pressure gradient (mean HVPG + SD = 16.30 + 6.06 mmHg).
      Such correlation prompted us to find a value for the level of laminin that more
      closely represented a HVPG of 12 mmHg, a well known threshold pressure for
      esophageal varices bleeding. At a cut-off concentration for laminin of 2.19 U/ml,
      sensitivity was 73%, specificity 60%, the positive predictive value was 85% and
      the negative predictive value 43%. In this study population, with a prevalence of
      75% of a HVPG > or = 12 mmHg, the diagnostic accuracy for such levels of serum
      laminin was 70%. CONCLUSIONS: Although a valid attempt in having a non invasive
      parameter for the investigation of portal hypertension, peripheral serum laminin
      alone doesn't seem to be a reliable marker for predicting portal hypertension and
      to assess the risk of variceal bleeding in patients with alcoholic cirrhosis.

PMID- 8751213
TI  - Injection sclerotherapy for oesophageal varices: a ten-year experience.
AB  - BACKGROUND/AIM: Severe hemorrhage from oesophageal varices is one of the most
      serious complications in patients with liver cirrhosis and portal hypertension,
      affecting about 30-70% of the former. This paper reports the results of treatment
      of oesophageal varices by injection sclerotherapy. PATIENTS AND METHODS: 89
      patients with oesophageal varices were treated with sclerotherapy in Oulu
      University Hospital in the period 1982-1991. The indication was acute bleeding in
      74 cases and prophylaxis in 15. RESULTS: Three patients died of rebleeding before
      eradication of the varices and nine afterwards. Rebleeding was more common in the
      Child B and C groups than in Child A (p < 0.01). Rebleeding did not correlate
      with the amount of sclerosant used. The most common complication was oesophageal
      stricture, noted in 15 patients, although only two required dilatation. This
      correlated with the amount of sclerosant used (P < 0.05). 34% of the patients
      died during the follow-up, the overall mortality rate being 14% in Child A cases,
      35% in Child B cases and 92% in Child C cases. Mortality was 26% among the
      patients receiving prophylactic sclerotherapy (4/15) and 35% among those with
      bleeding varices 35% (26/74). Five patients were operated on for rebleeding
      problems, four as emergencies and one electively. Two emergency patients died.
      CONCLUSION: While the number of patients in our group receiving prophylactic
      sclerotherapy was small, our results follow the general survival trend for
      bleeding varices.

PMID- 8751214
TI  - Sclerotherapy-resistant esophageal varices with enormously enlarged cephalad
      collateral vessels predictable using portography.
AB  - BACKGROUND/AIMS: The most common cause of failure of sclerotherapy is recurrent
      bleeding before eradication is complete. We investigated factors which would make
      feasible prediction of cases where esophageal varices would be more difficult to
      eradicate. PATIENTS AND METHODS: Seven hundred and seventy patients underwent
      endoscopic injection sclerotherapy at Kyushu University Hospital from January,
      1982 to June, 1989. For 580 of these patients we used the same sclerosant and a
      transparent overtube. For 19 of 580 patients over two months were needed to
      eradicate the varices (group 2), while eradication was complete in less than one
      month in 64 patients (group 1). RESULTS: There was a tendency toward a lower
      platelet count and a higher indocyanine green retention rate in group 2, but with
      no statistically significant difference. The number of sessions required for
      eradication of the varices was 8.1 +/- 2.5 and the total volume of sclerosant
      used was 98.2 +/- 62.3 ml in group 2, and 3.0 and 47.0 +/- 10.9 ml, respectively,
      in group 1 (p < 0.01). There was no significant difference in the number of
      sessions between the patients with large-sized and moderate-sized varices. Based
      on the extent of cephalad collateral vessels on the venous phase of celiac or
      superior mesenteric angiography, the vascular pattern could be classified into
      three types; Grade III, the most developed type was present in 100% and 57.1% on
      celiac and superior mesenteric angiography in group 2, while the rates were 11.1%
      and 5.6% in group 1 (p < 0.05). CONCLUSIONS: This retrospective study shows that
      in patients with enormously enlarged cephalad collateral vessels it may be
      difficult to eradicate the varices, and in such cases, preoperative portography
      is most useful to predict whether or not esophageal varices can be eradicated.

PMID- 8751215
TI  - The use of transjugular intrahepatic portosystemic shunt and surgical portocaval
      H-shunt for the treatment of colorectal variceal bleeding.
AB  - Surgical portocaval H-shunt was performed after the thrombosis of a transjugular
      intrahepatic portosystemic shunt inserted for colorectal variceal bleeding. The
      surgical procedure successfully controlled the variceal bleeding. However, the
      patient developed postoperative liver failure and hepatic encephalopathy due to
      complete portal vein thrombosis and the absence of prograde portal flow. This
      case illustrates the potential risks of the serial use of transjugular
      intrahepatic portosystemic shunt and surgical portocaval shunt leading to
      complete portal vein thrombosis, hepatic encephalopathy and acute liver failure.

PMID- 8751216
TI  - Histological analysis of hepatocellular carcinoma treated by intraarterial
      combined immunochemotherapy.
AB  - BACKGROUND/AIMS: We have previously reported the efficacy of intraarterial
      combined immunochemotherapy for 24 patients with unresectable hepatocellular
      carcinoma. This therapy consists of recombinant interleukin-2, OK-432,
      adriamycin, cyclophosphamide, and famotidine. We observed a complete response
      (CR) in 4, partial response (PR) in 3, minor response (MR) in 7, no change (NC)
      in 7, and progressive disease (PD) in 3. The response rate (CR+PR+MR) was 58.3%.
      The overall 2-year survival rate was 52%. The present study was designed to
      analyze the phenotype of tumor infiltrating lymphocytes and apoptosis-related
      antigen (Ley and Fas antigen) expression in tumor cells. MATERIALS AND METHODS:
      The analysis of phenotype of tumor infiltrating lymphocytes and apoptosis-related
      antigen (Ley and Fas antigen) expression in tumor cells were performed by
      immunohistochemical stain using resected specimens. RESULTS: Lymphocytes markedly
      infiltrated into the tumor lesions in treated patients compared with untreated
      patients. Phenotypes of tumor infiltrating lymphocytes were CD8+ and HLA-DR+. Ley
      positive and Fas-positive tumor cells were observed as well. Furthermore, in the
      strong lymphocyte infiltrating area, the Fas antigen in tumor cells were strongly
      expressed. CONCLUSION: In conclusion, the antitumor effect of intraarterial
      combined immunochemotherapy may be related with the activation of tumor
      infiltrating lymphocytes. These lymphocytes may kill tumor cells in an apoptotic
      fashion. Fas ligand expression of TILs should be determined in future.

PMID- 8751217
TI  - Optimal locoregional immunochemotherapy after tumor-mass reduction for advanced
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: This paper will give a description of our attempts to optimize
      the locoregional immunochemotherapy for advanced hepatocellular carcinoma.
      MATERIALS AND METHODS: A locoregional immunochemotherapy consisting of continuous
      recombinant interleukin 2 infusion and intermittent low dose doxorubicin
      injection was administered to a series of patients. RESULTS: Seventeen Stage IV
      HCC patients followed the protocol; 11 received IL-2 infusion for more than 6
      months, while 6 patients were suspended within 6 months because of new lesions or
      side effects from IL-2. After suspending IL-2 infusion patients continued to
      receive ADR injections. In the former group, excellent direct effect on liver
      tumors accompanied by increase in peripheral NK activity was observed. During
      periods of higher NK and LAK activity, direct effects on liver tumors were
      observed as complete remission (CR) in 4 patients and partial remission (PR) in 2
      patients. However, long-term observation of NK activity revealed intractable
      decrease after the 6th to 8th month despite an increase in IL-2 dose.
      CONCLUSIONS: We have shown the clinical usefulness of our locoregional
      immunochemotherapy after tumor-mass reduction in extending survival periods for
      advanced HCC patients. However, clinical effects of IL-2 immunotherapy were not
      observed in all patients. Further clinical and experimental studies are required
      to obtain longer-lasting enhancement of NK and LAK activity so that patient
      survival can be improved.

PMID- 8751218
TI  - Locoregional immuno-chemotherapy in liver carcinoma--present and future.
AB  - Locoregional infusion therapy has several theoretical advantages over systemic
      therapy for the treatment of primary or metastatic liver tumors. At present,
      hepatic arterial infusion (HAI) chemotherapy clearly improves the response rate
      over systemic therapy (approximately 40-60% vs. 10-20%). However, no definite
      survival benefit has been demonstrated. We have utilized immuno-chemo-combined
      locoregional therapy to treat liver malignancies, and are convinced that such
      therapy will bring promising results in liver malignancies for the following
      reasons: First, the liver is a large immunologic organ and possesses a large
      amount of lymphocytes/macrophages (Kupffer cells), whose antitumor activities are
      enhanced in a tumor-bearing state. Our strategy is to anticipate growth
      inhibition of the tumor and use combined chemotherapy at relatively low doses so
      as not to impair the anti-tumor activities of the lymphocytes. Moreover, some
      kinds of chemotherapeutic agents induce immunoaugmentation when low to moderate
      doses are used. Based on these reasons, we have conducted a pilot study of IL-2
      based immunochemotherapy for the treatment of unresectable liver metastases, and
      have obtained promising results. In this review, we have tried to delineate the
      locoregional immuno-chemotherapy in liver malignancies at present and future
      perspectives.

PMID- 8751219
TI  - Pancreatic head carcinoma: is pancreatic resection indicated for patients with
      stage III pancreatic duct cancer?.
AB  - BACKGROUND/AIMS: This paper examines factors influencing the outcome of patients
      suffering from unresectable pancreatic carcinoma. MATERIALS AND METHODS: One
      hundred forty-three patients with pancreatic carcinoma were placed into three
      groups. Group A (n = 56) received pancreatic resection. Group B (n = 30) included
      patients deemed ineligible for pancreatic resection. Group C (n = 57) was made up
      of patients deemed ineligible for pancreatic resection who received combined
      locoregional immuno-chemotherapy. RESULTS: Twenty-two patients (36%) from Group A
      are still living. Average survival is 18.6 months. Survival was dependent on the
      stage of the disease, the site of origin, and the type of resection. All Group B
      patients are dead with an average survival of 4.5 months and poor quality of
      life. Thirty-two patients (56%) from Group C are alive. Average survival is 21
      months and they have a much greater quality of life index compared to Group A or
      B. CONCLUSION: Based on the above results, we believe that for patients with
      Stage III Pancreatic Duct Carcinoma, pancreatic resection should not be the
      initial treatment option. These patients should be treated first with
      Locoregional Combined Immunochemotherapy. Then depending upon their response,
      should be assigned to a subsequent pancreatic resection.

PMID- 8751220
TI  - Third segment cholangio-jejunostomy in the treatment of unresectable klatskin
      tumors.
AB  - BACKGROUND/AIMS: Cholangiocarcinoma of the hepatic hilum is a seldom curable
      lesion when detected and several methods of palliation have been suggested.
      Bismuth has proposed an intrahepatic cholangiojejunostomy on the third segment of
      the liver, which in his experience obtains effective biliary drainage with better
      quality of life compared with other forms of palliation. PATIENTS AND MATERIALS:
      We have used this technique in nine cases. We evaluate results, mortality and
      morbidity, in comparison with other authors' reported series. RESULTS: In the
      early postoperative period one patient died, two patients suffered from immediate
      postoperative complications, and jaundice resolved completely in six patients.
      Long term survival was influenced by the underlying disease. CONCLUSION: Our
      findings support Bismuth preference for this technique of surgical palliation for
      non resectable tumors of the biliary tract.

PMID- 8751221
TI  - Needle tract implantation of hepatocellular carcinoma after ultrasonically guided
      needle liver biopsy: a case report.
AB  - Cancer spread along the needle tract following fine needle biopsy is reported to
      be a rare complication. We report a case of subcutaneous implantation of
      hepatocellular carcinoma (HCC) following ultrasonically (US)-guided fine needle
      liver biopsy. The patient, a 53-year-old male was found to have a HCC at the
      medial segment of the liver confirmed by fine needle biopsy. Three year and four
      months after segmentectomy, the patient felt a subcutaneous growing lump at the
      previous biopsy site. The tumor was resected and confirmed histologically as HCC.
      We herein document other reports of such an occurrence following fine needle
      biopsy of HCC in Japan and consider this problem in liver biopsies.

PMID- 8751222
TI  - Diagnostic ERCP in the era of laparoscopic surgery.
AB  - BACKGROUND/AIMS: The purpose of this paper is to reassess the place and risks of
      ERCP in a diagnostic view. METHODS: Analysis of 196 non-operative ERCP performed
      in 196 patients aged 57 +/- 20 yrs. ERCP was performed for: unexplained
      cholestasis = 98; non tumoral pancreatic diseases = 43; suspected neoplasm of the
      pancreatic/biliary tract = 13; cholangitis = 12; unexplained abdominal pain = 30.
      Precut papillotomy was performed in 40 cases (20.4%). 10.7% were cirrhotics; 3.1%
      were gastrectomized. 164/196 received peri-operative broad-spectrum antibiotics.
      RESULTS: 108 had normal ERCP (group I); 74 had abnormal ERCP (group II); 12 had
      undetermined diagnosis after ERCP (group III). Strictly ERCP-induced mortality
      was nil; 2 patients died a few days after ERCP from: hemorrhage after
      transhepatic drainage (1); continuing severe cholangitis after failed CBD
      cannulation (1). Morbidity was: acute pancreatitis = 6 (3%) and fever = 4 (2%).
      No complication followed precut papillotomy. The 6 pancreatitis recovered within
      48 h to 5 days. Fevers alleviated with antibiotics within 12 to 48 h.
      Pancreatitis occurred in 5/6 after normal ERCP; fevers followed pathologic ERCP
      in 3/4 (NS). The high rate of precuts in this series did not increase morbidity.
      CONCLUSION: ERCP-related morbidity was 5.1 % and ERCP accurately diagnosed or
      unequivocally eliminated biliary-pancreatic disease in 92.9%. These results
      suggest that ERCP remains a useful and safe diagnostic tool.

PMID- 8751223
TI  - Laparoscopic sonography: a real alternative to cholangiography during
      laparoscopic cholecystectomy?
AB  - BACKGROUND/AIMS: The routine use of intraoperative cholangiography (CGP) during
      laparoscopic cholecystectomy (LC) is still under debate. Previous reports suggest
      that intraoperative sonography can replace CGP in the evaluation of common duct
      lithiasis during open cholecystectomy. The present study was performed to
      evaluate the possible role of sonography during LC. PATIENTS AND METHODS: 45
      patients were submitted to laparoscopic sonography of biliary tree during LC. In
      all cases, CGP was performed. RESULTS: In 37 cases, sonography did not show the
      presence of stones; in 7 cases, common bile duct stones were identified by
      sonography; one false negative was observed. A sensitivity of 87.5%, a
      specificity of 100% and an overall accuracy of 97.8% were obtained. A false
      positive was obtained with CGP with a sensitivity of 100%, a specificity 97.3%,
      and an overall accuracy of 97.8%. CONCLUSIONS: Laparoscopic sonography can
      represent an adequate substitute for CGP as a screening procedure during LC.

PMID- 8751224
TI  - Extensive lymph node clearance for cancer of the esophagus or cardia: merits and
      limits in reference to 5-year absolute survival.
AB  - BACKGROUND/AIMS: The present study evaluates both merits and limits of extensive
      lymph node clearance in the mediastinum and upper abdomen on patients operated on
      more than 5 years ago. MATERIALS AND METHODS: One hundred forty-four esophageal
      cancer patients underwent subtotal (n = 97) or distal (n = 47) esophageal
      resection more than 5 years ago. Twenty-six patients operated on in a curative
      attempt were given radiotherapy (n = 14) or radiochemotherapy (n = 12). RESULTS:
      Esophagectomy with extensive lymph node clearance was feasible in 102 of the 144
      patients (70.8%). In-hospital mortality was 1.4%. Thirty-six patients lived more
      than 5 years, ie. 25% of all the esophagectomized patients and 35.3% (36/102) of
      those who were operated on in a curative attempt. Five-year absolute survival was
      38.4% after combined therapy v.s. 34.2% after surgery alone (p > 0.05). In the
      latter instance, it was 57.1% for those patients with normal lymph nodes v.s.
      14.6% for those with metastatic lymph nodes, and it was 64% for those with non
      transmural tumors v.s. 19.6% for those with transmural tumors. One half of those
      patients who were not given adjuvant therapy following esophagectomy with
      extensive lymph node clearance died of neoplastic spread, namely distant
      metastases (27.6%), cervical spread (3.9%), and local recurrence (10.5%).
      CONCLUSIONS: Esophagectomy with extensive lymph node clearance is not feasible in
      30% of the patients in whom it is attempted, and it does not prevent further
      neoplastic spread in one half of those in whom it is feasible. It is capable of
      curing 15 to 20% of those patients with locally advanced neoplasms and shelters
      90% of the patients from local recurrence.

PMID- 8751225
TI  - Manometric study of the upper esophageal sphincter before and after endoscopic
      management of Zenker's diverticulum.
AB  - BACKGROUND/AIM: Zenker's diverticulum treatment was done by endoscopic management
      of the elderly and debilitated patients without general anesthesia.
      MATERIALS/METHODS: With this technique, the septum between the diverticulum and
      the esophageal lumen is sectioned with a diathermic knife. Since the upper
      esophageal sphincter (UES) is certainly included in the mass sectioned, this
      accounts for the success of the procedure. RESULTS: Manometric assessment of the
      UES was done in 5 patients before the endoscopic treatment. The mean pressure was
      54.6 cm H2O and the mean length of 3 cm. A significant (p < 0.05) reduction in
      maximum pressure occurred postoperatively--mean 26.8 cm H2O. There was no
      significant variation in length of the UES. CONCLUSION: The maintenance of this
      basal pressure may be explained by the preservation of the circular muscle
      structure of the region, with sphincter-like characteristics.

PMID- 8751227
TI  - Solitary versus multiple gallstones: the importance of total biliary protein
      concentration and other factors.
AB  - BACKGROUND: Nucleating and antinucleating factors play an important role in the
      pathogenesis of cholesterol crystal nucleation. PATIENTS AND METHODS: In 88
      gallstone patients (59 female, 29 male) bile was examined for total biliary
      protein and glycoprotein concentration, nucleation time and cholesterol
      saturation index. Gallstone density was measured by in vivo computed tomography.
      RESULTS: Total biliary protein concentration was positively correlated with the
      number of gallstones (r = 0.84, p < 0.01) and higher in radiologically detectable
      isodense gallstones as compared to non-isodense stones (p < 0.01). A negative
      correlation between total biliary protein concentration, glycoprotein
      concentration and nucleation time was observed (r = -0.45, p < 0.01 and r = 
      0.49, p < 0.05). Nucleation time was significantly shorter in the case of
      multiple versus solitary stones (2.6 +/- 1.3 versus 8.5 +/- 3.0 days, p < 0.01).
      Cholesterol saturation index and biliary cholesterol concentration were similar
      in both cases, however a negative correlation between cholesterol saturation
      index and stone density (r = -0.79, p < 0.01) was found. No correlation was found
      between cholesterol saturation index and nucleation time (r = -0.04, p > 0.1),
      independent of gallstone number. None of the examined parameters was related to
      sex, age, weight or gallbladder function. CONCLUSIONS: Multiple gallbladder
      stones seem to be associated with shorter nucleation time and higher biliary
      concentrations of total protein and glycoprotein than solitary stones.

PMID- 8751226
TI  - Endoscopic Nd-YAG laser therapy as palliative treatment for esophageal and
      cardial cancer.
AB  - BACKGROUND/AIM: Progressive dysphagia is the most important symptom in inoperable
      cases of carcinoma of the esophagus and cardia. Treatment for the relief of
      dysphagia is chosen based on the lowest mortality and morbidity. This paper
      describes alpha consecutive series of patients with esophageal or cardial cancer,
      without a documented tracheoesophageal fistula, who were referred for palliative
      laser therapy. Alternative palliative treatments are discussed, as well as
      factors involved in successful laser treatment. MATERIAL AND METHODS: Over a five
      year period, 104 patients were treated endoscopically with the Nd-YAG laser for
      symptomatic improvement dysphagia caused by malignant tumors of the esophagus or
      cardia. RESULTS: After the initial laser therapy, good improvement was achieved
      in 78 patients (75%) and fair improvement in 17 patients (16%). Eighty-three
      patients with significant improvement were followed until death. In 42 of these
      83 patients, the initial laser therapy was the only treatment given; the
      remaining 41 patients required either additional laser treatment or other
      palliative therapy. CONCLUSION: Laser treatment for palliation in esophageal and
      cardial cancer is promising. Given the proper circumstances, it may lay the
      framework for many other important treatment modalities.

PMID- 8751228
TI  - Left-sided gallbladder with anomalies of the intrahepatic portal vein and
      anomalous junction of the pancreaticobiliary ductal system: a case report.
AB  - A 66-year-old man was admitted for an early cancer in the gastric corpus. At
      laparotomy, the gallbladder was located on the left side of the round ligament
      and attached to the lateral segment of the liver. This finding was compatible
      with a left-sided gallbladder. Postoperative ultrasonograms and portograms
      demonstrated anomalies of the intrahepatic portal vein as follows; The left
      umbilical portion and the posterior point of the portal branch were lacking. The
      posterior point was seen as an umbilical portion. An endoscopic retrograde
      cholangiopancreaticogram showed the cystic duct entering into the right side of
      the common bile duct confluent to the accessory pancreatic duct. A left-sided
      gallbladder unassociated with visceral inversion is a rare congenital anomaly.
      Forty-one cases have been reported in Japan, five with anomalies of the
      intrahepatic portal vein and two with anomalous junction of the
      pancreaticobiliary ductal system. To our knowledge, our patient is the only case
      of the left-sided gallbladder which both congenital anomalies.

PMID- 8751229
TI  - Stimulated gastrinemia, parietal cell mass and stimulated acid secretion in
      autonomous chronic gastritis: Helicobacter pylori influence.
AB  - BACKGROUND/AIMS: In the present experience, an evaluation has been carried out of
      stimulated gastrinemia, parietal cell mass, and acid secretion in the course of a
      paradigmatic condition, such as autonomous chronic gastritis, in order to reveal
      possible changes induced by the presence of Helicobacter Pylori (HP). MATERIALS
      AND METHODS: We evaluated 153 patients with chronic gastritis of the antrum
      and/or body fundus, in different combinations not associated with peptic
      pathology. RESULTS: In the group of subjects with antral superficial chronic
      gastritis associated with normal body-fundic mucosa or with body-fundic
      superficial chronic gastritis, about 40% of the subjects in the HP positive group
      show gastrinemia values which are higher than the norm. The evaluation of
      parietal cell and stimulated acid secretion yielded no differences between the HP
      positive and HP negative groups: it emerges that these parameters vary
      exclusively according to the histologic state of the body-fundic mucosa. In the
      patients group with hypergastrinemia, the study has revealed no variations in
      parietal cell mass and acid secretion. CONCLUSION: Evidently the increase in
      gastrinemia in these subjects was not important enough to induce an increase in
      parietal cell mass and acid secretion. It emerges how the presence of HP does not
      imply substantial changes on the gastric cyto-functional parameters: these
      variations depend mainly on the histologic state of the gastric mucosa.

PMID- 8751230
TI  - Follow-up on 242 patients with peptic ulcer disease one year after eradication of
      Helicobacter pylori infection.
AB  - BACKGROUND/AIMS: From Dec. 1990 to Jan. 1993 we treated 306 patients with chronic
      peptic ulcer disease and gastric Helicobacter pylori infection with one of three
      triple therapy regimens comprising bismuth subnitrate suspension (B) 15 mg/ml,
      oxytetracycline (OT), and metronidazole (M). METHODS: Treatment I (101 patients):
      B 5 ml, OT 500 mg, and M 200 mg, all q.i.d. for 14 days. Treatment II (60
      patients): B 10 ml and OT 750 mg q.i.d., M 400 mg t.i.d. for 7 days. Treatment
      III (145 patients): B 10 ml and OT 500 mg q.i.d., M 400 mg t.i.d. for 10 days.
      Gastroscopy and 14C-urea breath test were performed 4 weeks and 1 year after
      cessation of therapy. RESULTS: According to the urea breath test, H pylori
      eradication rates at 4 weeks were 87.9%, 81.9%, and 95.0% for Treatment I, II and
      III, respectively. At one year, 4 out of 242 patients, who were H pylori negative
      at 4 weeks, had become H pylori positive, i.e., H pylori reinfection rate 1.7%,
      95% CI 0.5-4.2%. Only one of these "reinfected" patients had ulcer recurrence.
      Another patient had duodenal ulcer recurrence shortly after cessation of
      treatment in spite of being H pylori eradicated, i.e., ulcer recurrence rate
      0.8%, 95% CI 0.1-3.0%. CONCLUSIONS: During the first year after H pylori
      eradication by triple therapy, recurrence rates of H pylori infection and peptic
      ulcer are very low (below 4.2% and 3.0%, respectively).

PMID- 8751231
TI  - Relationship between hematogenic metastasis of gastric cancer and the maximum
      extent of venous invasion by cancer cells in the gastric wall.
AB  - BACKGROUND/AIMS: The prognosis or the incidence of hematogenic metastasis after
      operation in patients with gastric cancer with venous invasion by cancer cells is
      still unclear. MATERIALS AND METHODS: The correlation was examined between venous
      invasion by gastric cancer and the occurrence of hematogenic metastasis in
      patients with gastric cancer at stage t2 (tumor had invaded muscularis propria or
      subserosa). RESULTS: The incidence of venous invasion by cancer cells in 228
      patients with t2 gastric cancer was 53.5%, as determined histologically. Between
      1977 and 1993, 32 of these 22 patients died from hematogenic metastasis. Thirty
      of the 32 patients (93.8%) with hematogenic metastasis had evidence of venous
      invasion by cancer cells of the gastric wall. Furthermore, 17 of the 30 patients
      (56.7%) had venous invasion at the subserosal layer of the stomach (ssv).
      However, of 196 patients without hematogenic metastasis, 92 patients had venous
      invasion and only 8 of 92 patients (8.7%) had ssv. The mean maximum extent of ssv
      in 8 patients without hematogenic metastasis was 2.28 mm but it was 4.76 mm in 17
      patients with hematogenic metastasis (P = 0.028). CONCLUSION: Thus, the
      hematogenic metastasis of gastric cancer was very closely related to the presence
      of extensive venous invasion by cancer cells of the subserosal layer in the
      gastric wall.

PMID- 8751232
TI  - Management of gastric cancer patients with synchronous hepatic metastasis: a
      retrospective study.
AB  - BACKGROUND/AIMS: In order to improve the management of patients of gastric cancer
      with synchronous hepatic metastasis, their records were retrospectively studied.
      MATERIALS AND METHODS: From January 1981 to July 1993, 558 gastric cancer
      patients were admitted in our institute. Twenty-five with synchronous hepatic
      metastasis were used in this study. Among these 25 patients, six had hepatic
      metastasis alone and nineteen had some other additional noncurative prognostic
      factors. For the primary lesion, 12 patients received gastrectomy (total or
      distal subtotal) and 13 patients did not. For the hepatic metastasis, 12 patients
      had regional therapy (hepatectomy or hepatic arterial chemotherapy) and 13 had
      not. Both gastrectomy and regional therapy for hepatic metastasis were carried
      out in 6 patients who had hepatic metastasis alone. RESULTS: Five year cumulative
      survival rate was 9%. Survival rate of patients with hepatic metastasis alone was
      significantly better than the patients with additional noncurative factors (p <
      0.05). The two long term survivors in this study had no other noncurative factors
      except hepatic metastasis. CONCLUSIONS: Neither gastrectomy nor regional therapy
      for hepatic metastasis had beneficial effects on the patients with additional
      noncurative factors. Gastrectomy and regional therapy for hepatic metastasis
      should be performed in patients without additional noncurative factors.

PMID- 8751233
TI  - Synchronous and metachronous primary malignancies in organs other than the
      stomach in patients with early gastric cancer.
AB  - BACKGROUND/AIMS: We investigated the outcomes of patients with early gastric
      cancer, with special reference to the prognosis of patients with synchronous or
      metachronous primary malignancies in organs other than the stomach. PATIENTS AND
      METHODS: Among 890 patients with early gastric cancer, 97 (10.9%) had synchronous
      or metachronous primary malignancies in organs other than the stomach. Ten-year
      survival rates were compared between patients who had additional malignancies and
      patients who had early gastric cancer but no other malignant disease (control
      group). RESULTS: Synchronous primary malignancies were detected in 32 patients
      and metachronous primary malignancies were detected in 65 patients (17 had
      developed before gastrectomy and 48 developed after gastrectomy). Hepatic cell
      carcinoma, lung cancer and colorectal cancer were frequently detected between 2
      and 24 years after gastrectomy. The 10-year survival rate was 80.8% for 769
      patients in the control group but it was only 49.7% for the 92 patients with
      additional malignancies. Moreover, metachronous malignant disease was found more
      over 10 years after gastrectomy in 30 of the 48 cases (62.5%). CONCLUSIONS: These
      results suggest the importance of long-term follow-up for detection of
      metachronous carcinomas at sites other than the stomach for patients with early
      gastric cancer.

PMID- 8751234
TI  - Effects of omeprazole and lansoprazole on fasting and postprandial serum gastrin
      and serum pepsinogen A and C.
AB  - BACKGROUND/AIMS: The aim of this study was to examine effects of two H+/K(+)
      ATPase antagonists (omeprazole and lansoprazole) on fasting and postprandial
      serum gastrin and serum pepsinogens A and C. MATERIALS AND METHODS: In 8 healthy
      volunteers, either 20 mg of omeprazole or 30 mg of lansoprazole once daily for 7
      days were administered in a double blind and randomized design. After a two-week
      period to "wash out" the drug, each treatment was then crossed over. Fasting and
      postprandial serum gastrin and serum pepsinogens A and C levels were measured at
      baseline and at the end of the treatment. RESULTS: Omeprazole increased fasting
      levels of serum gastrin and serum pepsinogen A and C. A similar finding was
      observed after lansoprazole administration. The test meal increased serum gastrin
      level but did not serum pepsinogens A and C either before or after omeprazole and
      lansoprazole administration. In addition, the integrated meal stimulated
      incremental serum gastrin were not modified after omeprazole and lansoprazole
      administration. CONCLUSIONS: This data suggests that both omeprazole and
      lansoprazole increase fasting serum gastrin and serum pepsinogen A and C levels,
      but have no effects on postprandial serum gastrin and pepsinogens levels.

PMID- 8751235
TI  - Immunohistochemical detection of endotoxin in endotoxemic rats.
AB  - BACKGROUND/AIMS: Although there are various methods to detect endotoxin mainly
      after the intravenous injection of purified endotoxin in a host, its uptake and
      distribution among the various organs is not well understood. In the present
      study, the time course of the distribution and disappearance of endotoxin in
      various rat organs following injection via two different routes was evaluated by
      an immunohistochemical staining method using a newly developed monoclonal
      antibody against Factor C. MATERIALS AND METHODS: The time course of the
      distribution of lipopolysaccharide (LPS) into the liver, spleen, lung, and kidney
      after intravenous (i.v.) or intraperitoneal (i.p.) injection of LPS was studied
      by immunohistochemical staining using a newly developed monoclonal antibody
      against Factor C in rats. Moreover, plasma endotoxin levels were measured by a
      modification of a chromogenic endotoxin-specific assay. RESULTS: At 30 minutes
      after injection in the i.v. group and at 12 and 24 hours in the i.p. group,
      endotoxin was present on Kupffer cells by staining and on some sinusoidal
      endothelial cells in the liver as well as on macrophages in the marginal zone of
      the spleen. The plasma endotoxin levels in the i.v. group decreased gradually
      after injection. However, levels in the i.p. group gradually increased, reaching
      a maximum level at 6 hours after injection, and then gradually decreasing.
      CONCLUSION: These results suggest that, regardless of the route of injection,
      endotoxin can be detected by an immunohistochemical staining method using a
      monoclonal antibody against Factor C.

PMID- 8751236
TI  - The role of interleukin-6, interleukin-16, tumor necrosis factor-alpha and
      endotoxin in hepatic resection.
AB  - BACKGROUND/AIMS: The role of cytokines was investigated in patients undergoing
      hepatic resection. MATERIALS AND METHODS: Cytokines such as interleukin-16,
      interleukin-6 and tumor necrosis factor-alpha were serially measured both before
      and after hepatic resection. RESULTS: The levels of interleukin-16 and
      interleukin-6 increased immediately after operation, while that of tumor necrosis
      factor-alpha was only slightly elevated. The increase in interleukin-6 was more
      prominent than that in interleukin-16. The level of urinary polyamine was
      elevated at postoperative day 1, while the level of C-reactive protein reached a
      peak at postoperative day 3. Moreover, no endotoxin in either the peripheral or
      portal vein was ever detected in this series. Regarding the comparison between
      major (more than 2 segments) and minor (less than 1 segment) resections, no
      significant difference was found in the levels of interleukin-1 beta, interleukin
      6 or urinary polyamine. CONCLUSIONS: Therefore, interleukin-6 is considered to be
      a more sensitive marker of surgical stress than interleukin-1 beta and CRP, while
      both interleukin-6 and interleukin-16 are suggested to induce hepatic
      regeneration and the production of acute phase protein in the liver. Furthermore,
      the absence of any correlation between the volume resected and those cytokine
      levels suggests that some other as yet unidentified mechanism could be also
      related to the regulation of hepatic regeneration.

PMID- 8751237
TI  - Rat liver pit cells following administration of the glycopeptide preparation
      (Polyerga).
AB  - BACKGROUND/AIMS: Pit cells are specific liver population which has been shown to
      express NK activity against tumor and viral target cells. We investigated the
      influence of the glycopeptide preparation (Polyerga) as one of the biological
      response modifiers on liver pit cells of male Wistar rats. MATERIALS AND METHODS:
      The number of pit cells was counted by light and electron microscopy in perfusion
      fixed liver sinusoids. An electron microscopical cytochemical staining for
      endogenous peroxidase was done. RESULTS: After a single intramuscular injection
      of Polyerga, a 3-to 6-fold increase in the number of pit cells was observed
      within a period of 1 to 7 days. Wide contact without specific junctions between
      pit cells and Kupffer cells was frequently detected. Granules, rod-cored vesicles
      and their closely related structures empty vesicles as well as hypertrophied
      Golgi apparatus were accumulated in the cytoplasm of pit cells next to contact
      surface. The number of ribosomes and polysomes in pit cell cytoplasm was
      significantly increased, which suggests activated protein synthesis. CONCLUSIONS:
      These changes are considered to represent the morphological expression of pit
      cell activation. It is concluded that the glycopeptide preparation Polyerga can
      induce proliferation of activated pit cells in the rat liver.

PMID- 8751238
TI  - Duodenum-preserving resection of the head of the pancreas--modified procedures
      and long-term results-.
AB  - BACKGROUND/AIMS: Relief of chronic pancreatitis can be accomplished surgically or
      with medication. Surgical treatment of pancreatitis should preserve the endocrine
      and exocrine function of the pancreas. This paper details the results of our
      modified procedure for resecting the head of the pancreas. The advantage of this
      procedure is small resection, preservation of endocrine and exocrine function,
      complete relief of pain by the pancreatic duct drainage and maintenance of
      function of the duodenum and bile duct. PATIENTS AND METHODS: Duodenum-preserving
      resection of the pancreatic head with denervation of the body and tail of the
      pancreas was performed in 41 patients with severe chronic pancreatitis. RESULTS:
      Mortality after a median follow-up period of 36 months was 2.4%. Complete relief
      or alleviation of pain were found in 92% of patients and any other patients of
      recurrent pain due to postoperative pancreatitis was not found. Eighty-seven
      percent of patients had maintained more than preoperative body weight.
      Postoperative glucose tolerance was unchanged in 88% of patients. After long-term
      follow-up postoperative exocrine function had been maintained at preoperative
      condition. CONCLUSIONS: Our procedure can maintain endocrine and exocrine
      function of the pancreas, relieve pain well and prevent pain due to recurrent
      pancreatitis.

PMID- 8751239
TI  - Intraportal endovascular ultrasonography as a new diagnostic procedure in
      pancreatic surgery.
AB  - BACKGROUND/AIMS: This presents the results of a prospective study on the use of
      intraportal endovascular ultrasonography (IPEUS) as a screening tool for
      pancreatic carcinoma. PATIENTS AND METHODS: Twenty-four patients with pancreatic
      cancer (17 head, 7 body) were studied for portal vein invasion using intraportal
      endovascular ultrasonography (IPEUS). In 22 cases, IPEUS was performed
      intraoperatively from the superior mesenteric venous route with an 8-French, 20
      MHz intravascular ultrasound (IVUS) catheter, in two cases preoperatively from
      the percutaneous transhepatic route with a 6- French, 20 MHz IVUS catheter. The
      sonographic criterion for detection of portal venous invasion was obliteration of
      the echogenic band of the portal vein. The IPEUS results were compared with those
      of CT and portography. RESULTS: Vascular invasion was confirmed with resected
      specimens in nine cases and with operative findings in three patients. For
      diagnosis of portal venous invasion, the sensitivity, specificity, and overall
      accuracy of IPEUS were 100%, 91.7%, and 95.8% respectively. For portography, the
      equivalent values were 66.7%, 75%, and 70.8%, while those for CT were 75%, 66.7%,
      and 70.8%.

PMID- 8751240
TI  - Intraoperative quick immunoperoxidase staining: a useful adjunct to routine
      pathological diagnosis in pancreatic carcinoma.
AB  - BACKGROUND/AIMS: This paper presents the results of a study comparing
      conventional and quick immunostaining. This paper aims to introduce the
      reliability of the immunoperoxidase method for rapid intraoperative pathological
      diagnosis of pancreatic cancer and the quick staining method. MATERIALS AND
      METHODS: Intrapancreatic extension and intraperitoneal spread of pancreatic duct
      cell carcinoma were evaluated by both conventional and quick immunostaining using
      antibodies against cancer-associated antigens CA19-9, DUPAN-2, and CEA for
      intraoperative pathological examination during the course of laparotomy. RESULTS:
      For the surgical cut margin, malignant lesions were identified in six of 30 cases
      by H-E staining. However, cancer cells were detected in 14 of 30 cases by the
      immunostaining method. On peritoneal washing cytological examination, malignant
      cells were recognized in four of 27 cases by conventional cytology. In two other
      cases, positive immunocytochemical findings were noted, and these clinical
      courses were suggestive of the immunostaining results. CONCLUSIONS: This
      immunostaining method was particularly useful in defining cancer cells surrounded
      by dense fibrous connective tissue and a very small number of cancer cells within
      the mesothelium, in which malignant cells are usually difficult to identify by
      conventional staining. Thus, the application of such immunostaining, together
      with conventional staining, on the cryostat sections of biopsy or on the
      peritoneal washings may provide sensitive information for intraoperative
      pathological examination and for selection of the appropriate surgical method.

PMID- 8751241
TI  - Surgical techniques of cytology-guided pancreatectomy for occult neoplasm of the
      pancreas.
AB  - BACKGROUND/AIM: In recent years, we have succeeded in treating an occult cancer
      of the pancreas by making the most of cytodiagnosis for the pure pancreatic
      juice. MATERIALS AND METHODS: Even for the patients in whom obvious tumor was not
      depicted by imaging techniques, the pure pancreatic juice was collected during
      endoscopic retrograde pancreatography and it was cytologically examined. RESULTS:
      When cancer cell was detected, both the location of occult lesion and the range
      of pancreatectomy were determined by the intraoperative cytology for the
      pancreatic juice which was collected separately from the cranial and caudal
      segments (2-segmental cytology). More recently, using a balloon catheter, the
      pancreatic juice of the head, body and tail, (3-segmental cytology) was examined.
      The former method was effective to prevent the blind resection of the entire
      pancreas, and the latter provided us with the opportunities to preserve much more
      pancreatic function. CONCLUSIONS: This method was a useful aid in resecting
      potentially curable cancer of the pancreas. The present paper introduces the
      detailed techniques of this method.

PMID- 8751242
TI  - Segmental pancreatectomy for the diagnosis and treatment of small lesions in the
      neck or body of the pancreas.
AB  - BACKGROUND/AIMS: To avoid any profound deficit in the pancreatic functions as
      well as to successfully make a histological diagnosis of such lesions, we
      performed resections of a small segment of the pancreatic neck or body. This
      article discusses the practicality of this procedure as well as the complications
      and evaluation of the pancreatic functions after surgery. PATIENTS AND METHODS: A
      segmental pancreatectomy was performed in patients with small lesions of the
      pancreatic neck or body. There were a total of 24 patients including 11 with
      hyperplasia, 7 with chronic pancreatitis, 4 with mucinous or serous cystadenoma,
      and each one with islet cell carcinoma (low-grade malignancy) and carcinoma in
      situ. RESULTS: No major complications occurred following surgery. The pancreatic
      endocrine and exocrine functions were well maintained in all patients except for
      two with chronic pancreatitis. CONCLUSIONS: Based on our findings, a segmental
      pancreatectomy for small lesions in the pancreatic neck or body seems to be a
      safe and effective procedure for minimizing the postoperative deficit in the
      pancreatic functions, while it also allows for an accurate diagnosis of lesions
      that are often difficult to differentially diagnose for malignancy.

PMID- 8751243
TI  - Regional vascular resection using catheter bypass procedure for pancreatic
      cancer.
AB  - BACKGROUND/AIMS: To elucidate the indications for extended operation including
      main vessel resection in pancreatic cancer surgery, a clinical study was
      performed. The safety and clinical significance of portal vein resection in
      pancreatic cancer surgery have not yet been obtained in a large series. MATERIALS
      AND METHODS: Over a period of more than 10 years, 134 of 212 (63%) patients with
      pancreatic carcinoma underwent resection by extensive radical surgery. Portal
      vein resection was performed in 104 of 134 (78%) resected cases using catheter
      bypass procedure. The postoperative survival was investigated and a
      clinicopathological study was conducted. RESULTS: Operative death within 30 days
      after operation was observed in 11 of 134 (8%) resected cases. Postoperative
      survival rate correlated with the grade of portal vein invasion, which was
      diagnosed by preoperative or intraoperative portography. Survival for more than
      two years after operation was seen in cases of negative invasion on the margins
      of the resected specimens group even when portal system vein wall invasion was
      observed. CONCLUSION: Portal vein resection is performed safely using bypass
      procedure of the portal vein and is recommended to obtain a tumor-free surgical
      margin.

PMID- 8751244
TI  - DNA ploidy and S + G2M fraction (proliferative index) as prognostic determinants
      in human periampullary cancer.
AB  - BACKGROUND/AIMS: The aim of the present study was to investigate the relationship
      between pathological factors, DNA ploidy patterns, proliferative index and
      survival in a population of patients undergoing resection for adenocarcinoma of
      periampullary region. MATERIALS AND METHODS: DNA ploidy and proliferative index
      of periampullary cancer tissue was measured by flow cytometry in 73 patients who
      had undergone pancreatoduodenectomy. RESULTS: Seventy-four percent (n = 54) of
      cancers were diploid and 26% (n = 19) were aneuploid. The median survival time of
      patients with diploid cancers was 30.1 (s.d. 5.1) months and with aneuploid
      cancers was 16.0 (s.d. 2.9) months (p = 0.02). Kaplan-Meier survival curves
      showed that the patients with aneuploid cancers succumbed to recurrent disease
      within 40 months after surgery whereas 20% of patients with diploid cancers
      survived longer than 40 months. In patients with long survival (3 years) there
      was a significant difference between aneuploid and diploid cancers (p < 0.001).
      In the multivariate analysis, tumor location and tumor size are independent
      prognostic variables for the length of survival after resection of periampullary
      cancer. CONCLUSIONS: DNA ploidy pattern appears to be one important prognostic
      predictor in patients with "long term" survival after successful
      pancreatoduodenectomy for periampullary cancers.

PMID- 8751246
TI  - Role of angiography in carcinoma of the pancreas as a preoperative assessment.
AB  - BACKGROUND/AIM: One of the most important factors effecting the prognosis of
      pancreatic cancer is successful resection of the carcinoma. Proper staging is
      essential to such resections. This study attempts to prove the importance of
      angiographic diagnosis for surgery of the pancreas due to ductal carcinoma. Such
      diagnosis influences the determination for resection, which in turn impacts
      patient prognosis. MATERIAL AND METHODS: Angiograms of 54 patients who underwent
      extended pancreatectomy for ductal carcinoma were reviewed. Findings of the
      angiograms and portograms were classified to four types from the viewpoint of the
      grade of carcinoma invasion. The angiograms were then compared with pathological
      determination of carcinoma invasion and the results were compared with patient
      prognosis. RESULTS: When arterial invasion was not detectable or limited to
      intrapancreatic small branches, curative resectability and longer survival rates
      were expected. In patients with invasion to major arteries adjacent to the
      pancreas, some patient survival rates were significantly longer than others.
      CONCLUSION: We overestimated the degree of carcinoma invasion based on
      arteriography so often that we were not disappointed when aiming for curative
      resection even when contraindicated by arteriography. Angiography had an
      important role as a preoperative assessment in carcinoma of the pancreas in terms
      of curative resectability and survival expectancy.

PMID- 8751245
TI  - Surgical treatment of pancreatic ascites and pancreatic pleural effusions.
AB  - BACKGROUND/AIMS: Massive ascites and pleural effusions are uncommon but well
      documented complications of chronic pancreatitis. The present study reviews the
      results of surgical management of pancreatic ascites and pleural effusions of
      pancreatic origin. PATIENTS AND MATERIALS: From forty-nine patients with chronic
      pancreatitis presenting with ascites and/or pleural effusion of pancreatic
      origin, 31 were surgically treated. RESULTS: Nineteen had ascites only, ten
      pleural effusions and two presented with both conditions. Diagnosis of the
      internal pancreatic fistula was based on the findings of high amylase levels and
      elevated albumin content of the peritoneal and pleural exudates. Failure of
      medical therapy was the indication of surgical treatment in all patients.
      Thirteen were submitted to internal pancreatic drainage, 17 to external drainage
      and one to distal pancreatic resection. Eight of 17 externally drained patients
      were reoperated for intraperitoneal abscesses (2), infected pseudocyst (1), pain
      recurrence (3) and pancreatic fistula (2); whereas reoperation occurred in only
      one of the 13 patients submitted to internal drainage (p < 0.05). CONCLUSIONS:
      Internal pancreatic drainage was the ideal surgical treatment for patients with
      pancreatic ascites and/or pleural effusion that did not respond to medical
      treatment. When this was not feasible external drainage was successfully used as
      an alternative to pancreatic resection.

PMID- 8751247
TI  - Second primary lung cancer and relapse: treatment and follow-up.
AB  - During a 14-year period (1980-1993) second primary lung cancer or relapse was
      treated in 44 consecutive patients. Thirty-seven patients had synchronous (n =
      18) or metachronous (n = 19) second primary lung cancer. Ten synchronous tumors
      were ipsilateral and treated contemporarily with five pneumonectomies, three
      lobectomies and two double wedge resections. The bilateral synchronous lesions (8
      patients) were treated by staged bilateral thoracotomy (mean interval; 2 months).
      The first resection consisted of a lobectomy in six patients and wedge resection
      in two. The second one was a wedge resection in six patients and a lobectomy in
      two. In the metachronous presentation 15 patients (79%) were asymptomatic and
      detected by follow-up chest X-ray. In this group the first operation was a
      lobectomy in 12 patients, a wedge resection or segmentectomy in 6 and a
      pneumonectomy in 1. The second one was a wedge resection in nine patients, a
      lobectomy in six and completion pneumonectomy in four. Seven patients, all of
      them asymptomatic, had local recurrence from their primary lung cancer. The first
      lung resection was a lobectomy in five patients and a wedge resection in two. The
      second one was completion pneumonectomy in five patients and completion lobectomy
      in two. We had no operative death. The actuarial over-all 5-year survival rate
      after the second pulmonary resection for second primary lung cancer was 38.3%
      with a median survival time of 13.5 months. The synchronous presentation had a
      better survival than the metachronous one (46.2% and 25.9%), respectively). The
      actuarial overall 5-year survival rate for patients with relapse was 38.1% with a
      median survival time of 37 months. We may conclude that an aggressive surgical
      approach is safe, effective and warranted in patients with either a second
      primary lung cancer or relapse from their primary lung cancer. Moreover, for
      early detection of the second lesions, follow-up at a maximum of 6-monthly
      intervals should be continued for more than 5 years after the first resection.

PMID- 8751248
TI  - Is a third mediastinoscopy really useful?
AB  - The value of a second remediastinoscopy in the diagnostic assessment of new or
      recurrent lung cancer have never been evaluated before. We retrospectively
      reviewed our experience with a third mediastinoscopy in the staging of lung
      cancer to define its role. In 13 patients a third mediastinoscopy was performed;
      in all cases the indication was suspected or proven new or recurrent lung cancer.
      All accessible lymph nodes were sampled. The technical aspects of the procedure
      are described. Nine patients with a negative third mediastinoscopy underwent
      subsequent surgery, four patients were not operated on, based on the positive
      histology and concomitant diseases. There were no major complications.
      Reremediastinoscopy can be performed safely and has proven to be helpful in
      defining potential surgical candidates. Mediastinal involvement can be excluded
      in most.

PMID- 8751249
TI  - The risk of stroke in the early postoperative period following mitral valve
      replacement.
AB  - All patients (285) undergoing mitral valve replacement (MVR) with a Carpentier
      Edwards (C-E) bioprosthesis +/- coronary bypass grafts (CABG) were reviewed (109
      men and 176 women with a median age of 70 years). Overall, the 5-year survival
      rate was 58.9%, 62.7% for MVR (199 patients) and 50.1% for MVR+CABG (86
      patients). Late survival was adversely affected by the operative time variables
      of NYHA class IV, older (> or = 70 years) age, low (> or = 56%) ejection fraction
      (EF), and the additional performance of associated procedures+CABG with MVR (P <
      or = 0.001). The 5-year freedom from stroke rate was 89.2%, 89.1% for MVR and
      90.2% for MVR +/- CABG. Advanced heart class was the only significant variable
      associated with a greater risk of late stroke (P < or = 0.01). Neither chronic
      preoperative atrial fibrillation nor operative obliteration of the left atrial
      appendage increased or decreased the late risk of stroke in patients following
      MVR. Hazard function for stroke occurring in the first postoperative year (first
      48 h excluded to discount intraoperative events) demonstrated the highest rate
      within the first month (40%), rapidly diminishing thereafter. This pattern was
      reproduced in the 12-year hazard function in that the rate of stroke occurrence
      was greatest in the first year (6.7%) following implantation. The mean stroke
      rate over 12 years was 2.5%. Strokes following MVR +/- CABG are more likely to
      occur in older and more compromised patients, and the higher early rate is not
      reflected in the mean rate. A more aggressive approach to early anticoagulation
      with IV heparin, Coumadin, and possibly antiplatelet therapy is advocated to
      reduce this complication rate.

PMID- 8751250
TI  - Improved results with mitral valve repair using new surgical techniques.
AB  - From January 1987 to July 1994, 299 consecutive patients ranging from 4 to 80
      years of age underwent mitral repair for pure valve insufficiency due to
      degenerative disease (59%), rheumatic disease (23%), endocarditis (12%) or
      ischemic heart disease (6%). During the initial period, a variety of reparative
      methods were used following the principles originally described by Carpentier.
      More recently, in our institution other surgical techniques have been introduced:
      specifically, prolapse of the anterior leaflet was corrected either by replacing
      the chordae with polytetrafluoroethylene (PTFE) sutures or simply by anchoring
      the prolapsing free edge to the facing edge of the posterior leaflet ("edge-to
      edge" technique). Chordal transposition has also been used occasionally to
      correct the prolapse of the anterior leaflet. The hospital mortality rate was
      1.3%. According to actuarial methods, the overall survival rate was 94% at 7
      years, and freedom from reoperation was 86%. Significant incremental risk factors
      for reoperation were: no use of prosthetic ring, correction of the prolapse of
      the anterior leaflet by triangular resection or chordal shortening and ischemic
      etiology of the mitral insufficiency (freedom from reoperation at 7 years was
      61%, 56% and 51%, respectively). In the late postoperative period (mean follow-up
      3.6 years), 95% of the patients were in NYHA class I or II; four patients had
      thromboembolic episodes, two hemorrhagic complications and two endocarditis. No
      patient in whom the prolapse of the anterior leaflet was corrected by the
      recently introduced technique has required reoperation. The anterior mitral
      leaflet prolapse was therefore neutralized as an incremental risk factor for
      reoperation and this has contributed to the improved overall results of mitral
      valve repair.

PMID- 8751251
TI  - Can the location of the large septal artery be predicted?
AB  - The aim of this study is to establish anatomical landmarks for the trajectory of
      the large septal artery. Thirty hearts were dissected, 20 of which had no cardiac
      pathology and the remaining with different cardiac conditions. One large septal
      artery was located in 27 of these hearts, two large septal arteries in 2 and
      three large septal arteries in 1. For all cases there existed one large septal
      artery in the lower border of the anterior limb of the septomarginal trabecula.
      When more than one large septal artery was encountered, the first was located
      within the subendocardial outflow tract of the left ventricle, the second was in
      the lower border of the anterior limb of the septomarginal trabecula and the
      third 1.5 cm below the second.

PMID- 8751252
TI  - Semilunar valve switch in aortic insufficiency.
AB  - The use of the Ross procedure in young patients is gaining wider acceptance. The
      need for a foreign pulmonary valve that will require replacement, however, is a
      serious drawback. To circumvent this problem, we reimplanted the native aortic
      valve in the pulmonary position in four patients (ages 12, 15, 15 and 17 years
      old) operated on utilizing the Ross procedure for aortic insufficiency. One
      patient had congenital and three isolated rheumatic aortic insufficiency. The
      root replacement technique with coronary artery reimplantation was used. All
      patients did well initially with marked reduction of left ventricular dilatation
      and good function of the reimplanted native aortic valve. One patient, however,
      died a month later from rupture of a false aneurysm that developed at the
      pulmonary autograft to ascending aorta anastomosis. We feel that the use of the
      native aortic valve in the pulmonary position makes the Ross procedure more
      attractive and potentially curative. The diseased aortic valve works well in the
      pulmonary position because of lower pulmonary artery pressure and resistance.

PMID- 8751253
TI  - Residual cognitive dysfunctioning at 6 months following coronary artery bypass
      graft surgery.
AB  - Neuropsychological testing is a sensitive method for quantitative assessment of
      cognitive dysfunctioning following cardiopulmonary bypass (CPB). However, the
      methodological problems associated with this method, such as learning effects due
      to repeated testing and the effects of distress on test performance, have often
      been underestimated. In this study, these confounding effects were controlled for
      by including the spouses of patients, exposed to the same potential stress
      effects associated with the operation, as a nonsurgical control group. The
      experimental group consisted of 63 patients (40-75 years) undergoing elective
      coronary artery bypass graft (CABG) surgery. A battery of standardized
      neuropsychological tests was administered to both groups 2 weeks preoperatively
      and 1 week, 1 month, and 6 months postoperatively. Statistical testing of inter
      group differences in preoperative to postoperative changes in test performance
      revealed the following results: (1) For immediate memory and learning, in general
      test scores showed the same time course for both groups. (2) For recent memory,
      patients' scores showed a significant deterioration at 1 month after CABG surgery
      compared with the scores of spouses. This effect had not completely disappeared
      at 6 months postoperatively. (3) For attention and psychomotor speed as well as
      verbal fluency, patients' scores had deteriorated significantly at 1 week after
      surgery, with incomplete recovery at 6 months. These negative cognitive effects
      were not related to the patients' ages or CPB parameters (duration of CPB, aortic
      cross-clamp time, mean flow and arterial pressure during CPB and aortic cross
      clamping, and minimum nasopharyngeal temperature). No differences in self-ratings
      of mood over time were found between the patients and spouses. The results
      indicate that, when adequately controlling for the effects of learning and
      distress, some cognitive functions are still impaired at 6 months after CABG
      surgery.

PMID- 8751254
TI  - Different results of cardiac transplantation in patients with ischemic and
      dilated cardiomyopathy.
AB  - We retrospectively analyzed 275 consecutive transplanted patients, dividing them
      into group A (128 patients) affected by ischemic cardiomyopathy and group B (147
      patients) affected by dilated cardiomyopathy. The difference in demographic,
      clinical and hemodynamic preoperative and postoperative data between the groups
      was studied; group A patients presented at transplantation with a less
      compromised hemodynamic picture, requiring inotrope infusion and mechanical
      assistance less frequently. The influence of etiology on early postoperative
      complications was also analyzed: group A patients needed postoperative mechanical
      assistance, inotrope, infusion and prolonged mechanical ventilation more often,
      therefore requiring a longer stay in the intensive care unit (ICU). Hospital
      mortality was twice as high in group A. The older age of group A patients per se
      did not influence these results significantly. The long-term follow-up was then
      studied with particular attention to parenchymal functions, hemodynamics,
      coronary artery disease, metabolic and surgical complications, and survival. The
      complication rate was higher in group A, with more severe hypertension and higher
      cholesterol levels at 1 year, a higher prevalence of accelerated coronary artery
      disease (CAD) and a more frequent onset of insulin-dependent diabetes. Surgical
      and vascular complications were also more frequent. The final result was a better
      5-year actuarial survival rate for group B patients. Donor and recipient ages at
      the time of transplant did not influence this result. We conclude that ischemic
      patients, even if they are transplanted in better condition and operated more
      electively, have a more critical early and long-term postoperative course and a
      worse survival rate. These findings are not explained by advanced age, but could
      be due to the impact of atherosclerosis and metabolic impairments associated with
      ischemic disease.

PMID- 8751255
TI  - Nitric oxide release during hypothermic versus normothermic cardiopulmonary
      bypass.
AB  - Cardiopulmonary bypass (CPB) produces hemodynamic and inflammatory disorders
      involving changes in vascular permeability and regional blood flow and
      alterations of coagulation and complement systems. It has been reported that an
      abnormal release of vasoactive substances during CPB, like bradykinin or nitric
      oxide, could play a role. The aim of this study was to investigate the changes in
      nitric oxide (NO) release occurring in patients undergoing CPB, under both
      hypothermic and normothermic conditions. Forty patients (mean age 61.4 +/- 8.4
      years) undergoing coronary bypass surgery were studied. In 20 patients (group A)
      systemic hypothermic CPB and antegrade cold intermittent crystalloid cardioplegia
      were used. The remaining 20 cases (group B) underwent surgery under systemic
      normothermic CPB and with antegrade warm blood intermittent cardioplegia. Nitric
      oxide was measured as the nitrite plasma level (NPL) by the Gries reaction. The
      time course of changes in NPL were obtained by collecting five whole blood
      samples: before CPB, 10 and 30 min after the start of CPB, and 10 and 60 min
      after the end of CPB. Although there were no significant variations of NPL
      shortly after the start of CPB (10 min after), values measured 30 min after CPB
      commencement and 10 min after the end of CPB showed a significant increase (P <
      0.0001) in both groups. Considering the two groups separately, NPL changes seemed
      to be similar, so independent of temperature; however, in group B higher values
      of NPL were measured during (30 min) and after (60 min) CPB (P < 0.0001). In
      conclusion, during CPB there is a progressive increase, independent of
      temperature in NO release.

PMID- 8751256
TI  - The value of parasternal mediastinoscopy in staging bronchial carcinoma.
AB  - Computed tomography (CT) is the non-invasive staging procedure of choice for
      assessment of metastasis to mediastinal lymph nodes in patients with bronchial
      carcinoma. Cervical mediastinoscopy can provide histologic evidence of
      mediastinal spread to the peritracheal, tracheobronchial and subcarinal lymph
      nodes. Sub-aortic and para-aortic nodes cannot be sampled via this route. The
      present study was performed to assess the staging value of the parasternal
      mediastinoscopy as a separate entity. Cervical and parasternal mediastinoscopy
      was performed in 37 patients with a proven diagnosis of non-small cell carcinoma
      of the left upper lobe. In 16 patients lymph node or tumor tissue could be
      biopsied via the parasternal route, in 21 patients no parasternal biopsy was
      taken. Of the 16 cases with biopsies, only one was positive (6%). Histologic
      examination of lymph node biopsy tissue was false negative in one other patient
      (6%). Of the 21 patients without biopsies taken during parasternal
      mediastinoscopy, three (14%) had proven lymphogenic spread to the subaortic and
      para-aortic nodes, detected at thoracotomy. The parasternal procedure changed
      treatment in only one patient (3%). Diagnostic sensitivity was 20%. It is
      concluded that parasternal mediastinoscopy should not be used as a routine
      staging procedure in patients with left upper lobe lung cancer.

PMID- 8751257
TI  - Modification of minitracheostomy technique to limit bleeding complications.
AB  - Minitracheostomy is a commonly performed procedure usually carried out by junior
      medical staff. Though there are few problems associated with the technique of
      minitracheostomy, bleeding is often encountered. We now present a brief case
      report demonstrating the problems associated with bleeding. We also outline an
      alteration in insertion technique with the 'Minitrach' designed to diminish the
      risks of serious bleeding, and report on our results with this technical
      modification.

PMID- 8751258
TI  - Coronary artery bypass surgery for patients with left main coronary lesions due
      to Takayasu's arteritis.
AB  - Two patients with documented Takayasu's arteritis and severe left main coronary
      lesion were operated on. The first patient was a 17-year-old boy operated with a
      double saphenous vein coronary artery bypass graft in 1982, the patient survived
      12 years but died suddenly due to associated aortic insufficiency. The second
      case was a 46-year-old female patient who was successfully operated on.

PMID- 8751259
TI  - Strangulated iatrogenic diaphragmatic hernia: a late diagnosed complication.
AB  - Three cases of iatrogenic diaphragmatic herniation are reported following
      thoracic and high abdominal surgery. Each case presented at least 6 months after
      the original surgery with symptoms of acute upper gastrointestinal obstruction.
      Diaphragmatic herniation was not considered in the initial differential diagnosis
      which lead to a delay in their referral. We emphasise the importance of checking
      the diaphragm following upper abdominal surgery and care when closing a defect.

PMID- 8751260
TI  - Left main bronchus compression after aortic reconstruction for interruption of
      aortic arch.
AB  - A case of the left main bronchus obstruction after an aortic reconstruction for
      interruption of the aortic arch is reported. Clinical features and successful
      management are described, and a mechanism for this complication is speculated on.

PMID- 8751261
TI  - Rapid two-stage arterial switch operation.

PMID- 8751262
TI  - Cefetamet pivoxil: comparable evaluation with other orally available antibiotics
      against selected species of respiratory pathogens.
AB  - Cefetamet pivoxil, the prodrug ester of cefetamet, is a new third-generation
      cephalosporin with a broad spectrum of activity. The in vitro activity of
      cefetamet was superior to that of cefaclor, ceftibuten, amoxicillin plus
      clavulanic acid, and amoxicillin alone when tested against 403 strains of freshly
      isolated upper and lower respiratory tract pathogens. Cefetamet killed 100%
      Haemophilus influenzae and H. parainfluenzae, including beta-lactamase-producing
      strains, at < or = 0.25 mg/l, Streptococcus pyogenes and S. pneumoniae at < or =
      0.5 mg/l, S. agalactiae at < or = 0.1 mg/l, and streptococci at < or = 2.0 mg/l.
      Moreover, at < or = 4 mg/l (breaking point), cefetamet was also highly effective
      against Escherichia coli (94%), Klebsiella pneumoniae (92%), K. oxytoca (91%)
      and, at 1 mg/l, against Moraxella catarrhalis (90%), including beta-lactamase
      producing strains. Furthermore, time-killing analyses at 4 x MIC demonstrated
      that cefetamet was bactericidal against beta-lactamase-producing H. influenzae,
      M. catarrhalis, and K. pneumoniae within 6 h and S. pneumoniae within 4 h.
      Hydrolysis studies confirmed cefetamet's stability to TEM1 and SHV1, the most
      common enterobacterial beta-lactamases.

PMID- 8751263
TI  - Comparative evaluation of orally active antibiotics against community-acquired
      pathogens: results of eight European countries.
AB  - In this multicenter study conducted in eight European countries, 13,173 pathogens
      -all isolated from community-acquired infections in 1992 and 1993--were evaluated
      for their susceptibility to the following orally active antibiotics: penicillin
      G, ampicillin, amoxycillin plus clavulanic acid, cefaclor, cefuroxime, cefetamet,
      doxycycline and erythromycin. Ten centers in Italy, five in Germany, in the
      Netherlands and Switzerland, four in Greece and Spain, three in Hungary and one
      in Finland contributed to this study; ready-to-use standardized microtiter panels
      (Sceptor system, BBL, Heidelberg, Germany) were used throughout all assays. The
      most frequently encountered species were: Escherichia coli, Proteus mirabilis,
      Klebsiella pneumoniae and non-typhoid Salmonella spp., Enterobacter cloacae,
      Streptococcus agalactiae, Haemophilus influenzae, Citrobacter freundii,
      Staphylococcus pyogenes, Streptococcus pneumoniae, Proteus vulgaris, Moraxella
      catarrhalis and Shigella spp. The percentage of susceptible isolates was assessed
      for each of the above-mentioned countries and European-wide with all the data
      available. For many species, the percentage of resistant isolates did not differ
      markedly between the countries considered. However, one of the most striking
      exceptions was the high prevalence of high-level penicillin-G-resistant S.
      pneumoniae isolates in Hungary and Spain; some of the low-level penicillin-G
      resistant strains remained susceptible to cefuroxime, whereas complete cross
      resistance occurred for all other beta-lactams studied. The high frequency of
      ampicillin-resistant H. influenzae isolates in Spain deserves mentioning; this
      could be attributed mainly to the prevalence of a beta-lactamase, as the addition
      of clavulanic acid rendered these strains susceptible to ampicillin. The
      penicillin compounds exhibited the greatest activity against Gram-positive
      pathogens, whereas cefetamet was the most active agent against Gram-negative
      pathogens with a well-balanced spectrum of activity.

PMID- 8751264
TI  - Gentamicin- and methicillin-resistant Staphylococcus aureus: phenotypic and
      genotypic characterization of three putative nosocomial outbreak strains.
AB  - Nineteen representative isolates of gentamicin- and methicillin-resistant
      Staphylococcus aureus (MRSA) were found to comprise three phenotypes; these
      differed with regard to hydrolysis of nitrocefin and production of staphylococcal
      enterotoxin A or/and toxic shock syndrome toxin-1. All MRSA isolates produced a
      capsule and were susceptible to coumermycin, nitrofurantoin, novobiocin,
      trimethoprim, trimethoprim-sulfamethoxazole, teicoplanin and vancomycin. All MRSA
      isolates were resistant to co-amoxiclav, ciprofloxacin, clarithromycin,
      gentamicin, methicillin, norfloxacin, ofloxacin, oxacillin and polymyxin B.

PMID- 8751265
TI  - High-level gentamicin-resistant enterococci: in vitro activity of double and
      triple combinations of antimicrobial drugs.
AB  - The ability of double and triple combinations of antimicrobials with different
      mechanisms of action, such as teicoplanin, meropenem, gentamicin and
      sparfloxacin, to achieve synergisms was investigated in vitro on some moderate
      level gentamicin-resistant (MLGR: 8 < or = MIC < or = 256 mg/l) and high-level
      gentamicin-resistant (HLGR: MIC > 500 mg/l) enterococci. On MLGR strains, a
      constant synergistic effect was achieved by a combination of teicoplanin with
      gentamicin or with meropenem, while generally addition, sometimes close to
      synergism, was exhibited by gentamicin-meropenem, gentamicin-sparfloxacin and
      teicoplanin-sparfloxacin associations. Triple combinations of teicoplanin,
      meropenem and gentamicin, or teicoplanin, sparfloxacin and gentamicin, always
      showed a remarkable advantage in terms of synergism over double combinations. On
      HLGR enterococci, the only double association showing an additive effect,
      sometimes close to synergism, was teicoplanin plus meropenem, while the triple
      combination of teicoplanin with gentamicin and meropenem always showed a marked
      synergistic effect. An effect very close to synergism was also shown by the
      combination of teicoplanin with sparfloxacin and gentamicin.

PMID- 8751266
TI  - Meropenem resistance in Pseudomonas aeruginosa.
AB  - Two genetically distinct classes of meropenem-low-susceptibility Pseudomonas
      aeruginosa PAO2152 mutants, which arose spontaneously, were isolated. Two
      meropenem resistance genes, mpmA and mpmB, were mapped near ilvB/C and proC,
      respectively, on the P. aeruginosa PAO chromosome. The mpmA was thought to be
      identical to oprD2 because of the cross-resistance to carbapenems and the
      association with the loss of the outer membrane protein D2 (OprD2). The mpmB
      mutation conferred a 4-fold increase in resistance to meropenem, and cross
      resistance to various types of antimicrobial agents, e.g. carbenicillin,
      norfloxacin and chloramphenicol. However, the mpmB mutant was susceptible to
      imipenem. This mutant still possessed OprD2 and showed increased expression of a
      48-kD outer membrane protein, although its profiles of beta-lactamase activity
      and affinities of penicillin-binding proteins for beta-lactams were
      indistinguishable from those of the parent strain. The resistance gene mpmB was
      considered to be an allele of nalB (or cfxB or oprK) from the results of the
      transductional analysis. The mutation frequency of mpmA:mpmB was in the ratio of
      4:1. The same results were obtained in another clinically isolated P. aeruginosa
      strain. Meropenem resistance caused by both mpmA and mpmB mutations seemed to be
      due to the reduction in permeability of antibiotics through the outer membrane.
      These findings suggest a new pathway for the translocation of meropenem other
      than that mediated by OprD2 across the outer membrane. Thus, meropenem showed
      about 4- to 8-fold higher activity than imipenem against OprD2-deficient P.
      aeruginosa.

PMID- 8751267
TI  - Herpes simplex virus-inhibitory sulfated xylogalactans from the red seaweed
      Nothogenia fastigiata.
AB  - Two sulfated xylogalactans (F1 and F7), isolated from the red seaweed Nothogenia
      fastigiata, achieved a dose-dependent inhibition of the replication of herpes
      simplex virus type 1 (HSV-1) in Vero cells, with 50% effective doses in the range
      of 15.0-32.6 micrograms/ml, and without affecting cell viability at
      concentrations up to 200 micrograms/ml. The presence of sulfate groups in the
      molecule was essential for the antiviral properties of these polysaccharides. F7
      afforded significant inhibition in HSV-1 yield if added to the cell cultures
      simultaneously with virus inoculum, but had no effect when it was added after 1 h
      of infection. Analysis of the early events of the viral replicative cycle showed
      that the anti-HSV effect of F7 was due to a specific inhibition of virus
      attachment to the host cell whereas virus internalization was not impaired.

PMID- 8751268
TI  - Changes in erythrocyte membrane lipids in breast cancer after radiotherapy and
      chemotherapy.
AB  - CMF and radiation treatment alter the erythrocyte membrane architecture in breast
      cancer patients by inducing free radical formation in the system. The increased
      free radicals hydrolyze the unsaturated fatty acyl chains of membrane
      phospholipids and thus alter the membrane lipid profile. To assess the
      erythrocyte membrane damage caused by CMF chemotherapy and radiation treatment
      among breast cancer patients and to find a way which can protect them from the
      observed toxic manifestations form the basis of this study.

PMID- 8751269
TI  - Haemophilus influenzae type b exoproducts induce chemotaxis and macrolide
      antibiotic release by human polymorphonuclear leukocytes.
AB  - The capacity of phagocytes to concentrate macrolide antibiotics was suggested by
      previous reports. In this study, we evaluated the capacity of Haemophilus
      influenzae type b culture supernatants (HICS) to induce polymorphonuclear
      leukocyte (PMNL) migration and macrolide antibiotic delivery. Using a Boyden
      multiwell chamber and a chemotaxis assay under agarose combined with a bioassay
      to measure antibiotic levels in agar, we demonstrated the chemotactic activity of
      HICS. Preincubation of PMNL with either erythromycin or azithromycin did not
      affect PMNL chemotaxis. By the agar diffusion test, we established that HICS
      increased the release of antibiotic from PMNL when compared with spontaneous
      release. Furthermore, we determined that the antibiotics remain bioactive after
      release. These results suggest that HICS may have a modulatory effect on
      transport and delivery of macrolide antibiotics by PMNL at the infection site.

PMID- 8751270
TI  - Bacteriological epidemiology and treatment of bacterial vaginosis.
AB  - One hundred symptomatic women with clinical bacterial vaginosis (BV) were
      enrolled in this study. The bacteriological epidemiology of BV and efficacy of
      oral or vaginal administration of antimicrobial agents for treatment of BV were
      investigated. The epidemiology of BV was investigated before antimicrobial
      therapy. Fifty patients were treated with oral administration of metronidazole
      (MTN), 500 mg twice a day, and 50 patients with 2% clindamycin (CLDM) phosphate
      in a vaginal cream, 5 g once a day for 7 days. The major organisms occurring were
      Streptococcus agalactiae, Escherichia coli, Gardnerella vaginalis,
      Peptostreptococcus species, Bacteroides species, Prevotella species, and
      Mobiluncus species and opportunistic pathogens such as Staphylococcus epidermidis
      and Enterococcus faecalis. The therapeutic efficacy of CLDM cream on BV appeared
      to be preferable to oral MTN from clinical and bacteriological aspects. The
      clinical and bacteriological effectiveness of MTN and CLDM in the treatment of BV
      suggests that anaerobes might play a major role in causing the clinical symptoms
      in patients with BV.

PMID- 8751271
TI  - Electronic identification with injectable transponders in pig production: results
      of a field trail on commercial farms and slaughterhouses concerning injectability
      and retrievability.
AB  - A nationwide electronic system for the identification of all pigs is a means to
      achieve a tighter control of livestock and meat in the Netherlands. In order to
      examine the use of electronic identification transponders, two field trails were
      performed. Transponders supplied by three separate companies were tested on pigs
      on commercial farms. In phase 1, each device was examined on separate farms and
      in phase 2, the three devices were tested on each farm. A total of 3,436 and
      5,947 transponders from the different suppliers were injected in the base of the
      ear at weaning in phase 1 and 2 on seven and five farms, respectively. The
      following aspects were examined: technical labour for injection and reading,
      readability of the transponders, impact on tissues at the injection site, and
      retrieval of the transponder after slaughter. After instruction the farmer was
      well able to inject a transponder in a restrained piglet. The results show that
      in phases 1 and 2 1.6% to 7.3% of the transponders were unreadable at retrieval
      in the slaughter line, which is significantly (p < 0.05) higher than the required
      maximum loss of 1%. The 1.6% failure rate in phase 1 involved transponders from a
      single supplier. Loss of identification was associated with rejection after
      injection, expulsion during inflammation and technical failure. Three weeks after
      injection on average 0.6% of the piglets had an observable inflammation and at
      the time of retrieval pus was found around, on average, 1.2% of the transponders.
      An average of between 37% and 88% of the transponders were retrieved in the
      slaughter line from the base of the ear in phases 1 and 2. The other transponders
      were retrieved medial or caudal to this position. This positional variation meant
      that it was not consistently possible to remove the transponder from the carcass
      within the required 4 second time period. It was concluded that the systems
      should be improved before recommending their introduction on a large scale,
      because the variation in readability and location is too high.

PMID- 8751272
TI  - A retrospective evaluation of adverse reactions to trimethoprim-sulphonamide
      combinations in dogs and cats.
AB  - Adverse reactions to various trimethoprim-sulphonamide (T-S) combinations were
      studied retrospectively in dogs and cats referred to the Utrecht University
      Department of Clinical Sciences of Companion Animals during the period 1985-1994.
      Dermatological and systemic reactions were observed in 19 dogs and 2 cats.
      Specific histological reaction patterns were seen in 3 dogs with toxic epidermal
      necrolysis, in 1 dog and 1 cat with erythema multiforme, and in 1 dog with
      pemphigus foliaceus. Diagnostic criteria used in humans proved to be reliable in
      dogs and cats as well. Adverse reactions were observed within 7-14 days after
      administration and were most often due to sulphadiazine (76%) and sulphatroxazole
      (14%). The incidence of adverse reactions to T-S was 0.25%.

PMID- 8751273
TI  - Comparison of the histological changes in the dog after treatment with the
      progestins medroxyprogesterone acetate and proligestone.
AB  - Administration of progestins in the dog may result in overproduction of growth
      hormone, suppression of the hypothalamic-pituitary-adrenocortical axis, and
      insulin resistance. In this paper we present a comparison of the histological
      findings in control dogs and dogs treated with either medroxyprogesterone acetate
      (MPA) or proligestone (PROL). Depot preparations of MPA or PROL were administered
      (SC) at 3-week intervals in two groups of seven ovariohysterectomized beagle
      dogs, after which three dogs of each group were killed. After a 6-month period
      without hormone treatment during which recovery was studied, the remaining dogs
      received five additional injections at the same interval and were subsequently
      killed. Tissue samples of four intact female beagle dogs served as controls.
      Progestin treatment resulted in atrophy of the adrenal cortex. In both MPA- and
      PROL-treated dogs, the thickness of the combined zona fasciculata and reticularis
      was significantly smaller than in control animals. In the mammary glands of
      progestin-treated dogs there were well developed alveoli and normal ducts
      adjacent to foci of hyperplastic ductular epithelium. Five dogs in each treatment
      group had developed benign mammary tumours which varied from simple tubular and
      papillary adenomas to benign complex and mixed tumours, whereas no mammary
      tumours were observed in the control animals. In each treatment group, steroid
      induced hepatopathy was observed in the liver of three dogs. Vacuolation of the
      cells of the islets of Langerhans and the epithelium of the intercalated ducts
      was present in two dogs of each treatment group and was only observed after the
      second series of progestin administrations. Incidental findings included chronic
      pyelonephritis, aspecific dermatitis, and mucinous dysplasia of the gall bladder.
      No abnormalities were found in sections of spleen, lung, brain, or pituitary
      gland. There were no significant differences in the frequencies of the various
      abnormalities between MPA- and PROL-treated dogs. Our findings correspond with
      the clinical and biochemical results after treatment of dogs with MPA and PROL.
      The high incidence of mammary tumours might be associated with our recent finding
      that in the dog progestins induce ectopic production of growth hormone in the
      mammary gland. The dog might be a good model for further studies on hormonally
      induced breast cancers.

PMID- 8751275
TI  - The fetlock tunnel syndrome: a macroscopic and microscopic study.
AB  - Chronic changes of several structures in around the fetlock tunnel can be a cause
      of the so-called fetlock tunnel syndrome (FTS) in the horse. Forty-nine annular
      ligaments (AL) from dead horses without a known history or clinical evidence of
      lameness and/or digital tendon sheath problems in these legs and 30 AL biopsies
      from horses suffering from FTS were studied macroscopically and microscopically.
      Macroscopically, the normal AL had a shiny white appearance, whereas the affected
      AL were often thicker and less white. Microscopically, the normal AL were about
      +/- 1 mm thick and were composed of undulating, parallel bundles of collagen.
      Small blood vessels with a diameter of 0.03-0.12 mm were found. The affected AL
      showed an increased thickness of collagen bundles, a changed direction of
      longitudinal axis of collagen bundles, and irregularly dispersed fibroblast
      nuclei. The number of blood vessels had increased, the external diameter of
      arteriolae could be up to 0.3 mm and arterial wall changes were observed.
      Possible relationships between the histological findings and the aetiology of the
      FTS are discussed.

PMID- 8751274
TI  - Pharmacokinetics of amoxicillin/clavulanic acid combination after intravenous and
      oral administration in goats.
AB  - The intravenous and oral pharmacokinetics of an amoxicillin and clavulanic acid
      combination (20 mg/kg of sodium amoxicillin and 5 mg/kg of potassium clavulanate)
      were studied in six goats. After intravenous administration the pharmacokinetics
      of both drugs could be described by an open two-compartment model. Amoxicillin
      had a greater distribution volume (0.19 +/- 0.01 l/kg) than clavulanic acid (0.15
      +/- 0.01 l/kg), whereas the distribution and elimination constants were higher
      for the latter, which was eliminated more quickly than amoxicillin. After oral
      administration of both drugs their pharmacokinetic behaviour was best described
      by an open one-compartment model with first-order absorption. Elimination half
      lives were twice as long after oral (2.15 +/- 0.20 h and 1.94 +/- 0.16 h for
      amoxicillin and clavulanic acid respectively) than after intravenous
      administration (1.20 +/- 0.16 h and 0.86 +/- 0.09, respectively). An apparent
      'flip-flop' situation was evident in this study. Bioavailability was 27% for
      amoxicillin and 50% for clavulanic acid.

PMID- 8751276
TI  - The phytohaemagglutinin (PHA) skin test as an indicator of stress-induced changes
      in immune reactivity in pigs.
AB  - The present study describes two experiments to standardize the
      phytohaemagglutinin (PHA) skin test as an indicator of lymphocyte reactivity in
      pigs after exposure to stressful situations in practical pig husbandry. The first
      experiment was a dose-response experiment. No time dose interaction was found, so
      the pattern of the reaction was the same for all doses used, although the
      magnitude of the reaction differed. The second experiment was carried out to
      determine stress-induced changes in lymphocyte reactivity. One half of a group of
      48 pigs was exposed to stress (mixing, moving, and an increased stocking
      density). The immune reactivity to intradermally injected PHA of stressed animals
      differed significantly (P < 0.01) from that of unstressed controls. The reaction
      of stressed animals can be characterized by a delayed reaction with a lower peak.
      It can be concluded that frequent measurements are preferable to single
      measurements when the effects of stress on immunological processes are studied.

PMID- 8751277
TI  - Antimicrobial resistance of Escherichia coli isolates from the faecal flora of
      veterinarians with different professional specialties.
AB  - The prevalence of antibiotic resistant Escherichia coli isolates from faecal
      samples from 110 veterinarians with different specialties (predominantly working
      with cattle, swine, poultry, or small animals or working as a non-practitioner,
      e.g. in government or industry) was investigated. In 22% and 13% of the
      veterinarians E. coli isolates showed a high level of resistance to
      oxytetracycline and ampicillin respectively. A significantly higher percentage of
      cattle practitioners had a high level of antibiotic resistance against ampicillin
      than did swine practitioners. Furthermore, a significantly higher percentage of
      poultry practitioners had a high level of antibiotic resistance against
      oxytetracycline than did swine practitioners and non-practitioners. A
      significantly higher percentage of practitioners recently (within last 6 months)
      used antibiotics for personal intake than did the group of non-practitioners.
      There was no evidence for a relationship between personal intake of antibiotics
      and the occurrence of a high level of resistance to ampicillin or
      oxytetracycline. The prevalence of E. coli isolates, that were resistant to
      several antibiotics was highest in cattle and poultry practitioners and the
      lowest in swine practitioners. A possible explanation for the observed
      differences in high level resistance to oxytetracycline and ampicillin between
      veterinary specialty groups is a difference in exposure to antibiotics during
      practice.

PMID- 8751278
TI  - Pseudorabies virus eradication by area-wide vaccination is feasible.
AB  - This article reviews the rationale for using marker vaccines and companion
      diagnostic tests in the eradication of pseudorabies virus (PRV). Recent advances
      in vaccinology and epidemiology indicate that, despite the inability to induce
      complete immunity, vaccination is a useful tool in the battle against PRV. This
      review focuses on the effectiveness of vaccination under field conditions and on
      herd, management and regional factors that are associated with PRV introduction
      or transmission.

PMID- 8751280
TI  - Changes in the gonadotropin-releasing hormone pulse generator activity during the
      estrous cycle in the goat.
AB  - The hypothalamic GnRH pulse generator activity, which was assessed by the
      characteristic increases in the multiple unit activity (MUA) specifically
      associated with the pulsatile LH secretion (MUA volleys), was monitored
      throughout the estrous cycle of the female goat. Blood samples were collected
      daily for analysis of progesterone, estradiol and LH levels to monitor ovarian
      cyclicity. The frequency of the MUA volleys showed a reciprocal relationship with
      the plasma progesterone profile; being low during the luteal phase, whereas
      increased during the follicular phase until the onset of the subsequent luteal
      phase. On the other hand, the duration of the MUA volleys changed in parallel
      with plasma progesterone levels showing considerable prolongation in the luteal
      phase. More frequent blood sampling was carried out at 2-hour intervals for
      timing the LH surge during the follicular phase induced by prostaglandin F2alpha
      (PGF2alpha) administration. During the PGF2alpha-induced follicular phase, the
      MUA volley frequency was abruptly increased from 4 h after PGF2alpha injection,
      and this high frequency was maintained throughout the follicular phase except for
      the period around the preovulatory LH surge when the MUA volley frequency was
      lowered temporarily. These results were in accordance with our previous
      observation that the recurrence of MUA volleys continued with decreased frequency
      during the estradiol-induced LH surge in ovariectomized goats. The present study
      revealed that GnRH pulse generator activity changes dramatically during the
      estrous cycle in the goat, and it is suggested that GnRH pulse generator activity
      becomes fully potentiated following luteolysis to induce the final follicular
      development and to stimulate estradiol secretion, which eventually provokes
      another neural mechanism responsible for the induction of the LH surge.

PMID- 8751279
TI  - A transient effect of estrogen on calcium currents and electrophysiological
      responses to gonadotropin-releasing hormone in ovine gonadotropes.
AB  - Episodic release of luteinizing hormone (LH) by the pituitary gland is controlled
      by hypothalamic gonadotropin-releasing hormone (GnRH). In the period leading up
      to the preovulatory surge of LH, estrogen increases the number of pituitary
      receptors for GnRH and sensitises the gonadotropes to GnRH. The postreceptor
      events that are responsible for the increase in responsiveness to GnRH are not
      clearly delineated, but LH release is known to be Ca2+ dependent. The present
      study addressed the question as to whether or not estrogen may act to modify
      voltage-dependent Ca2+ entry in normal gonadotropes. Primary cultures enriched in
      gonadotropes or somatotropes were produced from anestrous female sheep.
      Conventional whole-cell patch-clamp recording was used to measure inward membrane
      current in the absence of GnRH treatment, with and without 10 nM estradiol-17beta
      (E2) treatment for 0 to 36 h. Nystatin-perforated whole-cell patch-clamp
      recording was used to record membrane voltage responses to GnRH. Ca2+ current
      density (ICa, pA/pF) began to increase after 2 h exposure to E2, and reached peak
      values of about 200% of control by 16-20 h (p < 0.005), then declined. If E2 was
      withdrawn at 24 h, ICa returned towards control values by 36 h. If E2 treatment
      was continued beyond 24 h, however, ICa fell to about 75% of control by 36 h (p <
      0.005). Actinomycin D prevented the enhancement of ICa. E2 was without effect on
      Na+ current density in gonadotropes, or on ICa in somatotropes. The proportion of
      ICa carried by L-type and N-type channels in gondadotropes was not changed by E2.
      Ovine gonadotropes respond to GnRH with membrane potential fluctuations driven by
      periodic activation of Ca2+-dependent K+ channels, and synchronised action
      potential generation. This response was found to be sensitive to E2. Responses
      were categorised according to the pattern of activity evoked by 10 nM GnRH.
      Without E2 treatment, 11/14 cells responded with oscillations and 3/14 cells
      responded with spiking (hyperpolarizations following single action potentials).
      After 20 h 10 nM E2, just 1/14 cells responded with hyperpolarizing oscillations
      while 13/14 cells showed spiking activity. The predominance of the spiking
      pattern in E2-treated cells is consistent with the increased Ca2+ flux, and with
      enhanced LH release. We conclude that E2 has a transient effect on gonadotropes
      to enhance voltage-gated Ca2+ channel function. The time-course and biphasic
      nature of the influence of E2 on ICa may be physiologically appropriate to the
      preovulatory LH surge. Enhanced Ca2+ influx may participate in increased Ca2+
      dependent hormone release, while the delayed inhibitory action of E2 on ICa may
      serve to limit the duration of the surge.

PMID- 8751282
TI  - Expression and distribution of two gonadotropin-releasing hormones in the catfish
      brain.
AB  - The expression of prepro-catfish GnRH mRNA and prepro-chicken GnRH-II mRNA was
      investigated by means of in situ hybridization. The differential distribution of
      cells expressing the respective mRNAs was compared with the distribution of cells
      immunoreactive for (1) catfish (cf) GnRH and chicken (c) GnRH-II and (2) both
      GnRH-associated peptides (GAPs). It was found that the prepro-cfGnRH mRNA
      expressing cells were located in the ventral forebrain, with a similar
      distribution of the cfGnRH- and cfGAP-immunoreactive perikarya. The prepro-cGnRH
      II mRNA expressing cells were exclusively located in the midbrain tegmentum, at
      the same position as a group of large cGnRH-II- and CIIGAP-immunoreactive
      perikarya. It was concluded that the peptidergic neurons in the ventral forebrain
      contain cfGnRH, whereas cGnRH-II perikarya are restricted to the midbrain. The
      proximal pars distalis of the pituitary, containing the gonadotropin cells, is
      innervated by fibers immunoreactive for both cfGnRH and cfGAP and originating
      from the cfGnRH neurons in the ventral forebrain. We could, however, not detect
      fibers innervating the pituitary that were immunoreactive for cIIGAP.

PMID- 8751281
TI  - Progesterone suppression of glutamic acid decarboxylase (GAD67) mRNA levels in
      the preoptic area: correlation to the luteinizing hormone surge.
AB  - The progesterone-induced LH surge in the estrogen-primed rat is thought to be
      mediated through interneurons since LHRH neurons reportedly lack steroid
      receptors. Along these lines, glutamate and gamma-aminobutyric acid (GABA)
      neurons are considered to be two of the major interneurons in the hypothalamus
      involved in the control of LHRH and LH secretion. Glutamate is a major excitatory
      amino acid neurotransmitter while GABA is a major inhibitory amino acid
      neurotransmitter in the control of LH secretion. Glutamate is converted in the
      brain to GABA by the rate-limiting enzyme glutamic acid decarboxylase (GAD).
      Regulation of GAD by steroid hormones would therefore appear to be a logical
      mechanism for the control of LHRH and LH secretion based on the changes in
      glutamate and GABA production which would result from such regulation. Therefore,
      the purpose of the present study was to determine whether the steroid hormone,
      progesterone, regulates the GAD enzyme in the hypothalamus at a time when it
      induces an LH surge. To accomplish this aim, northern and dot blot analysis were
      used to measure GAD65 and GAD67 mRNA levels in the preoptic area (POA) and medial
      basal hypothalamus (MBH) in ovariectomized (OVX) immature rats, OVX rats primed
      with 2 mu g of estradiol (E2) for 2 days, and OVX rats primed with 2 mu g of E2
      for 2 days and administered progesterone (1 mg/kg, 09.00 h) to induce an LH
      surge. The results of the study show that GAD67 mRNA levels were suppressed by
      progesterone in the POA at 12.00 h (at the start of the surge) (24.4% suppression
      vs. E2 only; p <0.01) in the first experiment. This suppression was confirmed in
      a second experiment as progesterone suppressed GAD67 mRNA levels in the POA at
      12.00 h (31.8% vs. E2 only; p <0.05) and also at 14.00 h (40% vs. E2 only; p
      <0.05) which correlates to the peak of the LH surge. The changes in GAD67 by
      progesterone were restricted to the POA, as GAD67 mRNA levels in the MBH were
      unaffected by the steroid treatment. Furthermore, the effect of progesterone on
      POA GAD67 mRNA levels was specific as it was blocked by prior treatment with the
      antiprogestin, RU486 (400 mu g). In the MBH, both GAD67 and GAD65 mRNA levels
      were increased by estradiol treatment at 16.00 h and this increase was prevented
      by progesterone administration in the presence of estrogen priming. In
      conclusion, these studies demonstrate that the mRNA for the key enzyme
      responsible for the conversion of the major excitatory amino acid
      neurotransmitter in the hypothalamus (glutamate) to the major inhibitory amino
      acid neurotransmitter (GABA), is regulated by the steroid hormone progesterone.
      Progesterone suppression of GAD67 mRNA levels in the POA, where LHRH neurons
      reside, and at a time immediately preceding and during the LH surge, could
      provide a mechanism for greater stimulation of LHRH neurons through enhanced
      excitatory glutamate production concomitant with deceased inhibitory GABA
      production in the POA.

PMID- 8751283
TI  - A revised critical period for the sexual differentiation of the sexually
      dimorphic nucleus of the preoptic area in the rat.
AB  - The volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of
      the rat is several times larger in males than in females. Several studies have
      established the importance of gonadal steroids perinatally in the sexual
      differentiation of the SDN-POA as well as a critical period for the permanent
      influences of exogenous androgen on the volume of the nucleus. Recent preliminary
      evidence from this laboratory had suggested, however, that the critical period
      for the effects of the removal of endogenous gonadal steroids on SDN-POA volume
      may not match that for the administration of exogenous gonadal steroids. A series
      of experiments was designed to examine further the effects of the removal of
      endogenous gonadal steroids on adult SDN-POA volume by castrating male rats at
      various ages. In spite of a rather clear definition of a postnatal critical
      period for the effects of exogenous steroid administration, the results of this
      study indicate that the volume of the SDN-POA is sensitive to the removal of
      endogenous gonadal steroids for a prolonged period of time, extending through at
      least day 29 postnatally. The data suggest that there may be multiple critical
      periods for the sexual differentiation of the SDN-POA and reinforce the concept
      that these critical periods are distinct from those for other sexually
      differentiated parameters.

PMID- 8751284
TI  - Lesions of the afferent catecholaminergic pathways inhibit the temporal
      activation of the CRH and POMC gene expression and ACTH release induced by human
      interleukin-1beta in the male rat.
AB  - A number of recent studies have suggested that interleukin-1beta (IL-1beta) is a
      major mediator contributing to the recruitment of the hypothalamo-pituitary
      adrenal (HPA) axis following infectious aggressions. Central catecholamines
      modulate the response of the HPA axis. To investigate the importance of the
      afferent catecholaminergic pathways in a pathophysiological situation, we used
      the intraperitoneal (i.p.) IL-1beta injection (mimicking peripheral infections)
      and we investigated the effects on the HPA responses to IL-1beta of bilateral
      neurotoxic (6-OHDA) deletion of the ventral noradrenergic ascending bundle (VNAB
      X). The VNAB is an essential stimulating pathway linking the brainstem and the
      paraventricular nucleus (PVN). We determined the time courses of a number of HPA
      variables up to 240 min after i.p. injection of IL-1beta. We followed: plasma
      ACTH and corticosterone (CORT) concentrations, AP POMC nuclear primary RNA
      transcripts, AP POMC nuclear intermediate transcript RNA, AP POMC cytoplasmic
      mRNA, and hypothalamus (HT) CRH cytoplasmic mRNA. Compared to sham-lesioned male
      rats, VNAB-X animals displayed: (1) a reduced increase in plasma ACTH, and to a
      lesser extent in CORT throughout the experimental period with a 85% inhibition at
      the peak (90 min); (2) an increase in AP POMC primary nuclear transcript and in
      AP POMC nuclear intermediate transcript RNAs which last 60 min, instead of
      sustained significantly higher levels up to 240 min; (3) a similar, although
      reduced inhibition in the corresponding POMC cytoplasmic mRNA; (4) an almost
      complete abolishment of the marked biphasic rise in HT CRH mRNA. In conclusion,
      activation of the HPA axis by peritoneal IL-1beta challenge involves CRH
      producing neurons, and afferent catecholaminergic innervation of the PVN plays a
      crucial role in the signaling machinery linking the peritoneal aggression to the
      HPA axis.

PMID- 8751285
TI  - A study on the role of circulating prostaglandin E2 in the adrenocorticotropin
      response to intravenous administration of interleukin-1beta in the rat.
AB  - It is almost generally agreed that prostaglandins (PGs), especially PGE2, may
      play a significant role in mediating corticotropin-releasing hormone (CRH) and
      adrenocorticotropin (ACTH) secretion by interleukin (IL)-1. The origin and site
      of action of PGE2 involved in this response appear to be within the brain, but
      the possibility has yet to be excluded that circulating PGE2, which increases
      after a systemic administration of IL-1, enters the brain to stimulate CRH and
      ACTH release. In this study, we attempted to answer the question utilizing in
      vivo experimental paradigms in conscious male rats. Intravenous bolus injection
      of recombinant human IL-1beta (3 mu g/kg) caused a prompt and robust rise in
      plasma ACTH (peak, 748 +/- 183 (-x +/- SE) pg/ml at 20 min), but this was not
      associated with a significant change in plasma PGE2 up to 120 min
      postadministration. Intravenous bolus injection of PGE2 at doses of 0.1 mg and
      1.0 mg/kg BW resulted in dose-dependent significant elevations of the plasma ACTH
      with peak levels being 155 +/- 27 pg/ml (at 10 min) and 343 +/- 35 pg/ml (at 20
      min), respectively. Peak PGE2 levels in the plasma which occurred 10 min after
      injecting either dose of PGE2 were 13,245 +/- 5,093 and 57,150 +/- 350 pg/ml,
      respectively. Thus the ACTH response which followed the plasma PGE2 levels of
      13,000-57,000 pg/ml was even lower than the ACTH response to IL-1beta which did
      not cause a significant rise in the plasma PGE2. We conclude from these results
      that circulating PGE2 is not involved in the ACTH response to intravenous
      administration of IL-1beta. It is thus very likely that the source and site of
      action of PGE2 mediating the hormonal response are in the brain. However, this
      study does not exclude a possible role for other circulating PGs in the IL-1beta
      stimulation of ACTH secretion in the rat.

PMID- 8751286
TI  - Regulation of neuropeptide Y and its mRNA by glucocorticoids in the rat adrenal
      gland.
AB  - The effects of glucocorticoids on adrenal neuropeptide Y (NPY) and NPY mRNA
      levels have been investigated on adult male rats of the Wistar strain
      subcutaneously injected twice a day with dexamethasone (5 mg/day), metyrapone (66
      mg/day) or solvent (NaCl 0.9%) for 2.5 days and sacrificed 2 h after the last
      injection. Dexamethasone induced a significant decrease in both the adrenal
      weight (30%) and the plasma corticosterone concentration (85%) but a significant
      increase of the adrenal NPY content (about 25%) as well as of its mRNA (0.8 kb)
      (> 100%), revealed by Northern blot analysis and by in situ hybridization.
      Dexamethasone was unable to affect significantly dopamine (DA), norepinephrine
      (NE) and epinephrine (E) content of the adrenals; in contrast, it induced a
      significant decrease (30%) of the plasma NE level. Metyrapone elicited a drop of
      the plasma corticosterone level (80%), but a rise (near 150%) of the plasma ACTH
      concentration associated with an increase (19%) of the adrenal weight, a
      significant increase (30%) in the amount of adrenal NPY as well as a rise (>
      200%) of NPY mRNA content of the adrenal. Such treatment increased DA and NE
      (40%), and decreased E (> 30%) content of the adrenals. Metyrapone-induced
      changes of catecholamine concentrations in the plasma were similar to that
      observed in the adrenal gland. Data suggest that the increase in adrenal NPY mRNA
      content induced by dexamethasone is more likely due to humoral effect rather than
      nervous effect of this synthetic glucocorticoid on the adrenal medulla. A neural
      mechanism as splanchnic nerve activation in response to severe corticosterone
      deficiency is a reasonable hypothesis to explain the increase in adrenal NPY mRNA
      induced by metyrapone, although there are probably other, nonneural mechanisms by
      which metyrapone could stimulate adrenal NPY. Present data are consistent with
      glucocorticoid regulation of NPY gene expression and/or steady-state level of NPY
      mRNA in the adrenal gland.

PMID- 8751287
TI  - Rapid and long-lasting increase in galanin mRNA levels in rat adrenal medulla
      following insulin-induced reflex splanchnic nerve stimulation.
AB  - Expression of the neuropeptide galanin in the adrenal gland is rapidly induced by
      reflex stimulation of the splanchnic nerve following insulin-induced
      hypoglycemia. Here, we examine the cellular localization and mechanism of galanin
      mRNA upregulation in the adrenal gland after insulin administration, by Northern
      blot and in situ histochemical hybridization analysis. A 5- to 16-fold increase
      in galanin mRNA levels, measured by Northern blot hybridization using a rat
      galanin cRNA probe, was observed after insulin-induced hypoglycemia. An increase
      in galanin mRNA levels could be detected as early as two hours after
      administration of a single dose (10 U/kg) of insulin (Iletin II), consistent with
      the increase in galanin peptide levels in the adrenal gland within 24 h of
      insulin shock. Insulin-induced galanin mRNA upregulation was confined to the rat
      adrenal: neither hypothalamic nor pituitary levels of GAL mRNA were altered by
      insulin treatment. Adrenal galanin mRNA levels were maximally increased by 4 h,
      remained maximally elevated for at least 48 h, and had returned to baseline 6
      days after insulin administration. In situ hybridization analysis localized
      galanin mRNA induction to scattered groups of chromaffin cells throughout the
      medulla. These data demonstrate that regulation of GAL biosynthesis in the
      adrenal medulla occurs at a pretranslational level, and in a subpopulation of
      chromaffin cells. Rapid and robust upregulation of galanin biosynthesis in
      chromaffin cells upon insulin-induced splanchnic nerve stimulation suggests a
      hormonal or paracrine role for galanin in the adrenomedullary response to
      hypoglycemic shock.

PMID- 8751288
TI  - Effects of tetrodotoxin on osmotically stimulated central and peripheral
      vasopressin and oxytocin release.
AB  - Tetrodotoxin (TTX) was used to (1) distinguish between axonal and
      dendritic/somatic release of vasopressin (VP) and oxytocin (OT) within the
      supraoptic nucleus (SON) and (2) to determine whether neuronal inputs trigger
      intranuclear peptide release in the response to osmotic stimulation.
      Microdialysis was used to administer TTX (10(-6) M or 10(-4)M) bilaterally into
      the SON with simultaneous monitoring of central and peripheral peptide release
      and mean arterial pressure in urethane-anesthetized male rats. Osmotic stimuli
      were given via the microdialysis probe (1 M NaCl-artificial CSF) or injected
      intraperitoneally (3.5 M NaCl; 600 mu l/100 g b.w.) SON perfusion with TTX did
      not alter basal intranuclear VP or OT release or the intranuclear peptide
      response to direct NaCl stimulation of the SON. However, TTX treatment abolished
      the effect of peripheral osmotic stimulation on central peptide release. Basal
      plasma peptide levels were significantly reduced by TTX, e.g. decreases of 94.8
      and 75.8% for VP and OT, respectively. TTX also blocked the peripheral endocrine
      and cardiovascular responses to both modes of osmotic stimulation. The TTX
      insensitivity of directly stimulated intranuclear release suggests nonsynaptic
      peptide release from dendrites and/or cell bodies. The ability of TTX to abolish
      the central peptide response to systemic osmotic stimulation demonstrates that
      intranuclear release is a part of a cascade produced by osmotic activation of
      multisynaptic pathways.

PMID- 8751289
TI  - Nongenomic effect of glucocorticoid on the release of arginine vasopressin from
      hypothalamic slices in rats.
AB  - The arginine vasopressin (AVP) released from the hypothalamic slices containing
      paraventricular and supraoptic nuclei of Sprague-Dawley rats sectioned with
      vibratome and incubated in static microchambers was measured by radioimmunoassay,
      and the rapid effect and its underlying mechanism of glucocorticoids (GC) on AVP
      release were investigated. The results were as follows: (1) AVP was steadily
      released at a rate of 9.1 +/- 1.2 pg/min/well for as long as 6 h. (2)
      Corticosterone (B), within 20 min, inhibited AVP release in a dose-dependent
      manner from 10(-7) to 10(-4) mol/l. (3) Cortisol, 17beta-estradiol, or
      testosterone (all in 10(-6) mol/l) to some extent also inhibited AVP release, but
      dexamethasone, aldosterone, progesterone, RU 38486 or cholesterol had no
      significant inhibition on AVP release. (4) The rapid inhibitory effect of B was
      not affected by actinomycin D, puromycin or colchicine. (5) RU 38486 (10(-5)-10(
      3) mol/l) could partially block the rapid inhibitory effect of B, although it did
      not by itself change AVP release. (6) With the elevation of Ca2+ in the
      incubation medium, the AVP release was increased and the rapid inhibitory effect
      of B enhanced; while in the absence of Ca2+ the AVP release decreased and the
      effect of B attenuated. (7) The rapid inhibitory effect of B was enhanced in the
      presence of neomycin, although the latter had no influence on AVP release. (8)
      Aminophylline did not affect the rapid inhibitory effect of B. These results
      indicated that the rapid inhibitory effect of GC might be a nongenomic rather
      than the classical genomic one, and that the extracellular Ca2+ play a role in
      the rapid effect of GC on AVP release. The significance of the rapid action of GC
      in the rapid negative feedback regulation of AVP release from hypothalamus of
      rats was discussed.

PMID- 8751290
TI  - Intramedullary blood vessels of the spinal cord express V1a vasopressin
      receptors: visualization by a biotinylated ligand.
AB  - The neurohypophysial peptide hormone [Arg8]vasopressin (AVP) has well documented
      pressor effects in the periphery. These are mediated by vasopressin receptors
      (VPRs) of the V1a subtype, expressed by vascular smooth muscle cells, which
      induce vascular contraction when activated. AVP also has effects on the
      vasculature of the brain, where it has been reported to induce both vasodilation
      and vasoconstriction. The responsiveness of blood vessels of the spinal cord,
      however, has received little attention. To determine the morphology and
      distribution of blood vessels within the spinal cord, vessels were vizualised
      using a mouse anti-rat smooth muscle alpha actin IgG as primary antibody and
      fluorescein isothiocyanate-conjugated anti-mouse IgG secondary antibodies. A
      complementary vizualisation strategy which detected the endogenous peroxidase
      activity of red blood cells within vessels was also utilised. The characteristics
      of the structures observed using both visualisation strategies were typical of
      blood vessels. VPRs were localized using recently characterized high affinity
      biotinylated analogue of AVP (PhAcAL(Btn)VP), which is selective for the V1a
      subtype of VPR. PhAcAL(Btn)VP:VPR complexes were subsequently visualized by
      avidin-Texas red. The pharmacological characteristics of these sites were
      established using selective analogues of vasopressin and oxytocin. This confirmed
      that V1a receptors were indeed being visualized. The structures observed
      following visualization of VPRs had the same morphology as the vasculature
      revealed by the anti smooth muscle alpha-actin antibody. It can therefore be
      concluded that the blood vessels of the spinal cord express VPRs and are
      potentially responsive to AVP. Furthermore, VPRs were detected on capillaries of
      the microvasculature. As these capillaries are devoid of smooth muscle, VPRs must
      be expressed by endothelial cells as well as by smooth muscle cells. This
      distribution of VPRs would enable AVP to regulate local blood flow. The source of
      the AVP could be the general circulation, or perhaps more likely, to be local
      release from vasopressinergic hypothalamic neurones which are known to innervate
      specific regions of the spinal cord.

PMID- 8751291
TI  - On the treatment of subependymal giant cell astrocytomas and associated
      hydrocephalus in tuberous sclerosis.
AB  - Between 1980 and 1992, 10 children affected by tuberous sclerosis and
      intraventricular subependymal giant cell astrocytomas were surgically treated at
      the Institute of Neurosurgery, Section of Pediatric Neurosurgery, Catholic
      University of Rome. Nine patients presented with signs and/or symptoms of
      intracranial hypertension; in all of them the neuroradiological investigations
      demonstrated the presence of a space-occupying lesion in the region of the
      foramen of Monro with secondary ventricular dilation. In the remaining patient, a
      5-month-old male infant, an intraventricular mass was discovered by means of an
      ultrasound examination performed after the first epileptic fit. Three patients
      underwent a ventriculoperitoneal CSF shunt as first surgical procedure; in 2 of
      them it was subsequently necessary to remove the intraventricular tumor due to
      the frequent occlusion of the CSF shunt device. Seven subjects underwent the
      direct surgical excision of the lesion. In all of them the procedure resulted in
      the control of the associated hydrocephalus. On the basis of such an experience,
      the authors conclude that the surgical removal of the intraventricular tumors in
      patients with tuberous sclerosis and hydrocephalus is the most appropriate
      treatment. In fact, in the series considered here, the removal of the tumor was
      not accompanied by significant morbidity, and was followed by improvement in
      clinical conditions. In particular, in cases in whom the occurrence of
      hydrocephalus was associated with a worsening in the seizure disorder, the tumor
      removal and the correction of intracranial hypertension was followed by a
      significant reduction in frequency or even by the disappearance of the seizures.
      However, in no case presenting with mental impairment was a significant
      improvement observed in mental performances as a consequence of the surgical
      treatment.

PMID- 8751292
TI  - Functional magnetic resonance imaging for cortical mapping in pediatric
      neurosurgery.
AB  - Currently there is considerable interest in applying functional imaging
      modalities to the problem of cortical localization. We present the case of a 15
      year-old boy with a seizure disorder related to a tumor in the dominant
      supplementary motor area. This case illustrates the usefulness of functional
      magnetic resonance imaging as a new imaging tool for localization of cortical
      function in younger patients. The functional magnetic resonance imaging provided
      an anatomically accurate topographic map of operative site and subcortical
      structures along with relevant functional cortex. This information was useful for
      both presurgical planning and intraoperative localization. Validation of the
      technique in this instance was confirmed with intraoperative cortical motor
      mapping and the postoperative result.

PMID- 8751293
TI  - Long-term complications of hydrocephalus.
AB  - Problems may still occur for patients treated for infantile hydrocephalus who
      graduate to become adults, including unsatisfactory follow-up. We have continued
      the supervision in an adult institution of 70 children originally treated in the
      Birmingham Children's Hospital between 1974 and 1978. In these patients, 33
      (16.4%) of a total of 201 shunt revision procedures and 5 of the 8 subtemporal
      decompressions for slit ventricle syndrome were performed after the age of 16
      years. Similarly, 7 shunt infections occurred in this age group. Two patients
      died from a blocked shunt. Other late complications included blindness (n = 1),
      endocarditis (n = 1), and renal and heart failure requiring consideration of
      organ transplantation (n = 1). Also 2 patients developed clinical features of
      arachnoiditis following earlier lumboperitoneal shunting. An overall good long
      term outcome was observed. The majority of children graduated from a normal
      school (63%) or a school for physically handicapped children (21%). 67% of the
      patients are socially independent, but live at home with their parents. A further
      16% have left their parents' home and live either on their own (10%) or with
      their partners (6%). It is clear that although a good social and educational
      outcome is expected, significant clinical problems do arise during adulthood for
      patients shunted in infancy, even after a long period of apparent stability.
      Regular follow-up by surgeons familiar with these problems is essential.

PMID- 8751294
TI  - Cerebrospinal fluid shunt failure: late is different from early.
AB  - Six hundred and seventy-one operations to insert or revise simple, linear
      cerebrospinal fluid shunts were performed in a single institution from 1976
      through 1989. The results were analyzed using actuarial techniques. Failures
      within the first 8 months were defined as 'early', and subsequent failures were
      'late'. Patient age did not quite attain significance as a determinant of the
      risk of late shunt failure (p = 0.054). The following factors had no effect on
      the risk of late failure: interval since last operation, etiology of
      hydrocephalus, identity of surgeon, burr hole site, type of valve, and whether
      the shunt was new or revised. Modes of shunt failure in the two phases were
      compared: there were proportionately more infections among early failures and
      proportionately more fractures/separations among late failures (chi-squared =
      42.9, d.f. = 6, p < 0.000005). Shunts failing during the early phase were more
      often revised by removal and replacement of the entire system, whereas shunts
      failing later were more often revised by replacement of valve and/or abdominal
      catheter (chi-squared = 33.7, d.f. = 3, p < 0.000005). The late phase of shunt
      survival conformed very closely to an exponential decay model with a constant
      monthly risk of failure of 0.5% (r2 = 0.98). Contrary to intuition, cerebrospinal
      fluid shunts did not encounter increasing monthly risks of failure as they grew
      older. The contempt of familiarity has discouraged study of the mechanisms of
      shunt failure. Experience suggests that most early shunt failures are
      attributable to infection and other technical misadventures, but the mechanisms
      of late failure are distinct and incompletely understood.

PMID- 8751295
TI  - Lumbosacral agenesis: clinical characteristics, imaging, and embryogenesis.
AB  - We report 5 cases of complete, or nearly complete, agenesis of the lumbar and
      sacral spine. In 1 case pregnancy was terminated at 23 weeks of gestation, and
      the others were livebirths. The surviving 4 patients were all infants of diabetic
      mothers. Imperforate anus was present in 2 of 4 liveborn patients and was
      suspected in the abortus. All liveborn cases were paraplegic, and all exhibited
      the 'Buddha' deformity of the lower extremities. One patient had congenital
      obstructive hydrocephalus, probably representing a variant of holoprosencephaly,
      requiring a ventriculoperitoneal shunt. No other nervous system anomaly was
      identified in any patient, and the other patients are showing normal cognitive
      development. We propose that these patients have defects which occurred during
      germ cell formation (i.e., during gastrulation), with interruption of the
      primitive streak resulting in combined failure of primary and secondary
      neurulation.

PMID- 8751296
TI  - Encephaloceles of the anterior cranial fossa.
AB  - From a total of 114 encephaloceles treated surgically at The Hospital for Sick
      Children in the 15 years to 1994, the case records of 17 patients with sincipital
      and 5 patients with basal defects were reviewed retrospectively. The condition
      was evident at birth in 64% of patients, while the remainder presented with
      either cerebrospinal fluid (CSF) rhinorrhea, nasal obstruction, or feeding
      difficulty. Hypertelorism affected 73% of patients. All encephaloceles were
      repaired transcranially, at a mean age of 2 years, usually by means of an
      intradural pericranial graft. Five children with gross hypertelorism underwent
      orbital translocation at the time of encephalocele repair. Of those not
      corrected, primary and secondary hypertelorism regressed in most instances where
      the encephalocele was treated before the age of 2 years. There were no deaths.
      The only case of CSF rhinorrhea occurred in a patient with a basal defect, in
      whom intradural repair was not possible because of adherence of diencephalic
      structures to the sac wall. Hypertelorism recurred in 1 patient after orbital
      translocation, requiring recorrection 2 years later. One patient with untreated
      secondary hypertelorism failed to regress after the encephalocele was excised at
      the age of 4 months. Developmental outcome was normal in 59% of children, whilst
      18% have mild mental or physical disability, and 23% are severely impaired. A
      child with a sincipital or basal defect and mild hypertelorism should have the
      encephalocele treated in early childhood to allow the facial skeleton to remodel
      with growth. When an encephalocele is accompanied by gross hypertelorism or a
      facial cleft, one-stage correction can be undertaken safely in early childhood
      with minimal mortality and acceptable morbidity.

PMID- 8751297
TI  - Chondroid chordoma of the lateral skull base.
AB  - Clinical, radiological, and pathologic features of an intracranial chondroid
      chordoma in a 9-year-old boy are described. This is the first reported case of a
      chordoma, the center of which was laterally situated in the cranial base, lying
      in or near jugular foramen and carotid canal, but without midline involvement.
      Although cranial chordomas in childhood are extremely rare, and all previously
      reported cases appeared to have arisen in the clivus, this location should not be
      considered ectopic. Forking at the rostral end of the notochord has been
      demonstrated in embryos, and would be the presumed embryological source for this
      tumor. This is also the first reported case of a chondroid chordoma in a child
      with immunohistochemical documentation distinguishing it from a chondrosarcoma.
      This chondroid chordoma contained two populations of cells: neoplastic cartilage
      and chordoid tissue in a myxoid stroma. The distinction between chordoma and
      chondrosarcoma and the implications on treatment will be discussed.

PMID- 8751298
TI  - Multiple arteriovenous malformations of spinal cord and brain in a child.
AB  - A case of concurrent intracranial and spinal cord arteriovenous malformations
      (AVMs) is described. A 3-year-old girl presented with paraparesis, bladder-bowel
      disturbances and bilateral dysesthesia of the lower extremities due to a spinal
      hematoma, resulting from a spinal AVM. Magnetic resonance imaging revealed a
      hematoma and abnormal vessels in the spinal cord. The AVM was embolized with
      polyvinyl alcohol particles and silk sutures and was surgically removed. Later,
      this girl presented with disturbance of consciousness due to an intraventricular
      hemorrhage, resulting from a cerebral AVM. The cerebral AVM was surgically
      resected. The coexistence of bleeding cerebral and spinal AVMs is very rare.

PMID- 8751299
TI  - Haemoglobin-based red cell substitutes: current status.
AB  - Chemically modified haemoglobin solutions represent a potential alternative to
      the transfusion of donor blood. The theoretical advantages of these products
      include an oxygen delivery potential greater than that of conventional plasma
      expanders, prolonged shelf-life, universal compatibility and the absence of
      pathogenic viruses. Principal concerns have been safety issues including renal
      toxicity, coagulopathy and vasoactivity. The proposed indications for these
      solutions are primarily resuscitation of patients in haemorrhagic shock and
      perioperative haemodilution during elective surgery. Three products have now
      undergone phase I safety trials in human subjects and phase II safety and
      efficacy trials are planned in the near future.

PMID- 8751300
TI  - Large-scale production and properties of immunoaffinity-purified human activated
      protein C concentrate.
AB  - Activated protein C (APC) is a highly specific serine proteinase which functions
      as an important naturally occurring antithrombotic enzyme. APC also has anti
      inflammatory properties. We have developed a large-scale process for the
      production of APC for therapeutic use starting with cryoprecipitate-poor human
      plasma. This report describes the process, its performance at the pilot plant
      scale, and the characteristics of immunoaffinity-purified human APC concentrate
      referred to as APC (human). The process consists of three chromatographic steps,
      an enzymatic conversion step, and incorporates a solvent/detergent treatment step
      for the inactivation of lipid-enveloped viruses. Solvent/detergent was shown to
      rapidly inactivate spiked HIV-1, as well as three marker viruses to nondetectable
      levels under process conditions. The immunoaffinity-purified protein C (PC)
      intermediate was enriched 13,600-fold over plasma and had a specific activity of
      231 U/mg. The overall yield of the process following enzymatic conversion of the
      PC intermediate to APC and its processing by anion exchange chromatography was
      36%. APC (human) was shown to be highly purified, functional and stable.

PMID- 8751301
TI  - No detectable alterations in immunogenicity following terminal severe dry-heat
      treatment of high-purity factor VIII (Liberate) and factor IX (HP9) concentrates.
AB  - We used monoclonal antibody ELISAs, antigen molecular size distribution,
      competition ELISA and neonatal mouse immune tolerance methods to detect potential
      neoantigen formation and increased immunogenicity following severe dry-heat
      treatment of high-purity factor VIII (Liberate) and factor IX concentrates. To
      provide positive controls, concentrates were heated in solution (70 degrees C for
      2 h) to produce denaturation on purpose. The competition ELISA applied to factor
      IX proved particularly useful for quantifying differences between the positive
      control and the dry-heated/unheated concentrates. None of the test systems
      employed by us indicated any detectable neoantigen formation or any alteration in
      immunogenicity following terminal severe dry-heat treatment of the high-purity
      concentrates, and this finding is supported by clinical experience so far.

PMID- 8751302
TI  - A combination of two distinct in vitro amplification procedures for DNA typing of
      HLA-DRB and -DQB 1 alleles.
AB  - The differential hybridisation of oligonucleotide probes to polymerase chain
      reaction (PCR)-amplified DNA has become a standard procedure for tissue typing.
      We describe a typing method in which differential ligation replaces differential
      hybridisation, which is a significant simplification of this strategy. After
      amplification by the PCR two labelled, sequence-specific oligonucleotides
      hybridise, in the fluid phase, to one strand of heat-denatured amplification
      product in juxtaposition. In the case of perfectly complementary sequences
      surrounding the gap, a thermostable ligase catalyses the ligation of the two
      oligonucleotides, otherwise they stay separated. The use of heat-resistant ligase
      enables easy repetition of the denaturation-annealing-ligation cycle in a
      thermocycler. The ligation products are detected by an enzyme linked
      immunosorbent assay. We tested this typing approach in a model system, the
      characterisation of three functional alleles of HLA-DRB3 using three probe pairs.
      No discrepancies were observed in typing 100 individuals of known genotypes. A
      total of 33 probe pairs combined with generic and group-specific amplification
      allowed the typing of alleles of HLA-DRB and -DQB1 loci at low resolution. We
      confirmed ligation-based typing results of 259 individuals with sequence-based
      HLA-DRB1 typing and HLA-DQB1 typing using PCR with sequence-specific primers
      (SSPs). In addition, more than 1,500 ligation-based HLA-DRB1 typings were
      concordant with SSP typing. Excellent signal-to-noise ratios in the enzyme-linked
      immunosorbent assay make ligation-based typing remarkably robust. The time
      requirement of 2.5 h post-PCR enables practicable typing of putative organ
      donors. The whole procedure is more easily amenable to automation than methods
      based on differential hybridisation requiring additional incubators and extra
      handling for hybridisation and washing.

PMID- 8751303
TI  - Neonatal alloimmune thrombocytopenia in Taiwan due to an antibody against a
      labile component of HPA-3a (Baka).
AB  - We report on two siblings who developed severe neonatal alloimmune
      thrombocytopenia (NAIT) due to an alloantibody against a labile component or
      components of the HPA-3a (Baka) antigen. The antibody reacted only with fresh,
      unfixed platelets by the solid-phase red cell adherence test, immunofluorescence
      test and mixed passive haemagglutination test. In the latter method, weakly fixed
      platelets also gave a weak positive reaction. Monoclonal-antibody-specific
      immobilization of platelet antigens and immunoblotting tests gave negative
      results. Our findings may possibly help to explain why in some cases of NAIT no
      platelet-specific antibody is demonstrable in tests with fixed or solubilized
      platelets.

PMID- 8751304
TI  - An enzyme-linked immunosorbent assay for the quantitative determination of anti-D
      in plasma samples and immunoglobulin preparations.
AB  - Here we present an enzyme-linked immunosorbent assay (ELISA) on microtiter plates
      for the quantitative determination of anti-D. This method is based on the
      solubilization of red blood cells sensitized with anti-D and the subsequent
      measurement of immunoglobulin G by ELISA. The measuring range of the assay is 40
      5,000 IU/ml and the lowest quantifiable concentration in plasma is 0.5 IU/ml. The
      interassay relative standard deviation for concentrations above 130 IU/ml ranges
      from 3.2 to 8.1% and below 50 IU/ml from 10.5 to 19.7%. Comparison of ELISA with
      automated hemagglutination shows that the results of the two assays correlate
      well: r = 0.992, n = 26. The assay was validated for donor plasma samples and
      anti-D immunoglobulin preparations and it can also be used in assessing the
      severity of Rh (D) hemolytic disease during pregnancy.

PMID- 8751305
TI  - DNA-based typing of human platelet antigen systems by polymerase chain reaction
      single-strand conformation polymorphism method.
AB  - Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP)
      method has been established to discriminate genotypes for the human platelet
      antigen (HPA) systems HPA-1, HPA-2, HPA-3, HPA-4, and HPA-5. Gene fragments which
      contain polymorphic sequences corresponding to the HPA-1, HPA-2, HPA-3, HPA-4,
      and HPA-5 systems were PCR-amplified with specific primers. The amplified DNA was
      denatured and subjected to non-denaturing polyacrylamide gel electrophoresis
      followed by silver staining. The results obtained by the PCR-SSCP method were in
      good agreement with those of the allotypes determined by serological typing.
      Furthermore, the results agreed with those obtained by other DNA-based typing
      methods such as PCR-allele-specific restriction enzyme analysis and PCR-sequence
      specific primer. These results indicate that PCR-SSCP is a simple and sensitive
      method for determining HPA genotypes and identifying unknown polymorphisms.

PMID- 8751306
TI  - PCR detection of a low viral load in a prothrombin complex concentrate that
      transmitted hepatitis B virus.

PMID- 8751307
TI  - Post-transfusion hyperhaemolysis in a patient with sickle cell disease: use of
      steroids and intravenous immunoglobulin to prevent further red cell destruction.
AB  - Delayed haemolytic transfusion reactions (DHTRs) are seen more frequently in
      patients with sickle cell disease (SCD) than in other groups of patients, and are
      characterised by a positive direct antiglobulin test and the appearance of
      previously undetected red blood cell (RBC) alloantibodies in the patient's serum.
      Recently a syndrome of post-transfusion hyperhaemolysis has been described in
      children with SCD, characterised by destruction of both autologous and transfused
      RBCs with negative serological findings: continuation of RBC transfusion
      exacerbated haemolysis further. We describe a case of life-threatening post
      transfusion hyperhaemolysis in an adult patient with SCD in whom severe anaemia
      necessitated further RBC transfusion, which was successfully performed in
      conjunction with intravenous immunoglobulin. This approach may be useful in the
      management of post-transfusion hyperhaemolysis in SCD as well as in the
      management of severe DHTRs.

PMID- 8751308
TI  - Incorrect diagnosis of hepatitis C with RIBA-3.

PMID- 8751309
TI  - Nomenclature for factors of the HLA system, 1995.

PMID- 8751310
TI  - Persistence of the typical spike-wave EEG pattern after surgical excision of a
      temporal lobe astrocytoma and apical lobectomy.
AB  - This is a report on a patient with intractable 'primary' generalized seizures and
      typical spike-wave EEG patterns, in whom an unexpected temporal lobe astrocytoma
      was detected by MRI studies. Clinical and electrophysiological studies were
      performed before and after surgical excision of the tumor and apical temporal
      lobectomy in an attempt to determine whether 'primary' generalized seizures and
      EEG patterns and the temporal lobe tumor were only coincident neurological
      disorders or were indeed related. Before resection, the patient consistently
      showed a typical spike-wave EEG pattern with no background and paroxysmal
      activities suggestive of 'secondary' bilateral synchrony in 10 consecutive
      conventional EEG recordings; neither spontaneous interictal nor ictal ECoG
      activities suggested focal temporal lobe epileptogenesis. After resection, the
      patient showed increased pentylenetetrazol (PTZ) convulsive threshold, and
      reduction in the number of 'primary' generalized seizures, although typical spike
      wave EEG discharges persisted. These observations suggest that 'primary'
      generalized seizures, EEG patterns and the temporal tumor were
      physiopathologically interrelated, and that both reticulocortical and
      corticoreticular mechanisms may participate together in the genesis of 'primary'
      generalized clinical and EEG activities.

PMID- 8751311
TI  - Analysis of static and kinetic abnormalities typical of torticollis, and
      postoperative changes.
AB  - The clinical pattern of torticollis and surgical results were evaluated. Head
      posture and range of motion were measured. The authors use a newly designed
      device consisting of an orthogonal system to which head position is referred.
      Preliminary data were obtained on 24 patients with torticollis and 21 healthy
      control subjects. The examination of posture shows that the head usually twists
      in opposite directions simultaneously around a vertical and a sagittal axis, and
      the deflection is greater in one direction. Head position affect body posture,
      with the trunk often compensating for head deviation. Although there are almost
      always abnormalities on EMG recordings of neck muscles, these do not indicate the
      degree and pattern of deformity. Because of the disorder of muscle innervation,
      head movements are affected, with an asymmetrical decrease in the range of motion
      in comparison with normals (p < 0.05). Movements are greater toward the direction
      of postural deviation. Eleven patients were studied before and after undergoing a
      bilateral C1-C3 rhizotomy and selective section of the XIth rootlets, which carry
      motor fibers to the sternocleidomastoid muscle. Head posture immediately improved
      (p < 0.05), with better appearance, despite some residual distortion (less than
      10%), and trunk alignment also improved . In contrast to posture, head range of
      motion was worse than before (p < 0.05). The most improved movement was rotation,
      followed by flexion/extension. Further improvements were observed at later follow
      up. Surprisingly, the range of motion gradually increased, surpassing
      preoperative limits (p < 0.05). Our study documents the usefulness of surgery in
      correcting torticollis. Posture is immediately affected; motion increases despite
      denervation, after an initial decline.

PMID- 8751312
TI  - Vascular effects of spinal cord stimulation in the monkey.
AB  - Because of clinical reports suggesting beneficial effects of electrical
      stimulation in peripheral vascular disease, studies have been conducted in the
      monkey. Regional blood flow was measured prior to, during and following the
      application of electrical currents to the spinal cord. The flow measurements were
      made using radioactive microspheres. In addition, tissue temperatures and venous
      and arterial concentrations of epinephrine and norepinephrine were measured. The
      results show that electrical stimulation increases blood flow to the skin and
      muscle. It is hypothesized that the effect is due to sympathetic inactivation
      secondary to the application of electrical currents.

PMID- 8751313
TI  - Effect of spinal cord stimulation on cerebral blood flow in cats.
AB  - Effects of electric spinal cord stimulation (SCS) on cerebral blood flow (CBF)
      were investigated in anesthetized adult cats. SCS was performed under various
      stimulus conditions for 1 h via a wire electrode inserted into the dorsal
      epidural space at various levels in the spinal cord. CBF was measured in the
      subcortex of the parietal lobe by hydrogen clearance method before, during, and
      after SCS. After the start of SCS in the high cervical cord with a frequency of
      20 Hz, CBF gradually increased up to 140% of the pre-SCS value, and remained high
      for 15 min after the end of SCS. SCS of the low cervical or midthoracic cord
      under the same condition caused no significant increase in CBF. Nor did SCS of
      the high cervical cord with frequencies of 200 and 2,000 Hz increase CBF. No CBF
      increase was observed after SCS of the high cervical cord with 20 Hz when the
      dorsal column was sectioned at the medullo-cervical junction. These results
      suggest that the ability of SCS to increase CBF is peculiar to high cervical cord
      stimulation with moderately low frequencies.

PMID- 8751314
TI  - Thalamic stereotaxis for chronic pain: ablative lesion or stimulation?
AB  - Twenty-five patients underwent 33 stereotactic procedures on the thalamus for the
      treatment of persistent pain of benign or malignant origin. There were 19
      ablative and 14 stimulation procedures. The thalamic targets were the centrum
      medianum (CM), the pulvinar, the nucleus ventralis posteromedialis and/or the
      nucleus ventralis posterolateralis. Ablative surgery was successful in 52.6% of
      the procedures, and chronic stimulation in 66%. Stimulation in the
      ventroposterior group of the thalamus was most effective for peripheral
      deafferentation pain while ablative stereotaxis on the CM may be more appropriate
      for patients with central pain or cancer pain. ??

PMID- 8751315
TI  - Special issue on drugs and the elderly: use and misuse of drugs, medicines,
      alcohol, and tobacco, Introduction.

PMID- 8751317
TI  - Screening and diagnosis of "alcohol abuse and dependence" in older adults.
AB  - A literature review reveals that research is warranted to improve screening for
      "alcohol abuse" in older adults and women. An examination of diagnostic criteria
      for "alcohol abuse dependence" reveals that older adults provide unique
      challenges to classification systems. There is a need to evaluate the sensitivity
      and specificity of several new screening instruments for the identification of
      "alcohol abuse" in the elderly. Routine screening of elderly and women presenting
      in primary care settings should be a priority for researchers and clinicians.

PMID- 8751316
TI  - Epidemiology of problem drinking among elderly people.
AB  - The prevalence of alcohol use and misuse declines with age, but misuse remains an
      important public health problem among older people. Between 2 and 4% of the
      United States elderly population meet DSM-III criteria for "alcohol abuse" or
      dependence. Up to 10% are "heavy" or problem drinkers. Alcohol use and misuse are
      both more common among men than women. Since the elderly population is expanding,
      we will see an increase in the absolute number of older problem drinkers over the
      next few decades even if the prevalence of problem drinking remains constant. It
      is incumbent on health care providers and administrators to plan for the
      prevention and treatment of alcohol problems among these people.

PMID- 8751318
TI  - Medical manifestations of alcoholism in the elderly.
AB  - Alcoholism may lead to a great many physical and mental problems in individuals
      of any age. Elderly alcoholics often have additional problems resulting from the
      interaction of age related changes in physiology and "heavy" alcohol intake. Some
      of the more important problems are: Impairment of the immune system with
      decreased ability to deal with infection or cancer. Increased incidence of
      hypertension, cardiac arrhythmia, myocardial infarction, and cardiomyopathy.
      Increased incidence of stroke. Alcohol dementia. Increased incidence of
      esophageal and other cancers. Cirrhosis and other liver disease. Malnutrition.
      There seems to be no area in which even moderate alcohol intake is of definite
      benefit, and some areas in which even small amounts are detrimental.

PMID- 8751320
TI  - Treatment approaches for older problem drinkers.
AB  - Recent research suggests that older adults with alcohol problems often drink in
      response to loneliness, depression, and poor social support networks. Although a
      variety of approaches such as psychodynamic, Twelve Step, social support,
      behavioral, and cognitive-behavioral, have been suggested, only those studies
      involving behavioral and cognitive-behavioral interventions have provided
      empirical support for treatment effectiveness. Some research also suggests that
      age-specific group treatment produces better outcomes than when older adults are
      placed in treatment with younger alcoholics.

PMID- 8751319
TI  - Early versus late onset of alcoholism in the elderly.
AB  - The age of onset of alcohol-related problems is a typology that is gaining
      prominence among clinicians. Findings from epidemiological studies suggest that
      there are a significant number of older alcoholics who first begin to drink
      alcohol "abusively" in their later years. While few demographic differences
      appear between late onset and early onset alcoholics, a number of studies have
      reported clinical differences between these groups that may affect the natural
      course and treatment outcome of the illness.

PMID- 8751321
TI  - Alcoholism and dementia.
AB  - This article reviews epidemiological, neurological, cognitive, and imaging data
      on alcohol-induced dementia. Recent studies indicate that "heavy alcohol use"
      (variously defined) is a contributing factor in 21-24% of cases of dementia.
      Research difficulties include lack of positive diagnostic criteria, few post
      mortem studies, and no accepted pathological mechanism. Sulcal widening and
      ventricular enlargement (occasionally reversible) are the strongest findings in
      patients with alcohol-induced dementia. There is evidence for peripheral
      neuropathy, ataxia, sparing of language, and improved prognosis when patients
      with alcohol-induced dementia are compared to other dements. Case examples,
      etiologic theories, and recommendations for research, training, and clinical
      practice are included.

PMID- 8751322
TI  - Misuse of prescription drugs.
AB  - The elderly person is at risk of drug misuse and related problems because of
      frequent use of prescription drugs, biologic factors, and social circumstances
      associated with aging. Confusion, falls, and aggravation of untoward emotional
      states are examples of the adverse consequences. Diagnosis of drug dependency
      states is difficult because of the overlap of general medical disorders and
      mental disorders and a lack of suitable diagnostic criteria for the aged. Two
      case examples of drug misuse are given, and the management of drug misuse and the
      treatment of drug dependence on an inpatient and outpatient basis are discussed.
      Future research directions are suggested.

PMID- 8751323
TI  - Interactions between alcohol and other drugs.
AB  - More than 75% of people age 65 and older use medications. Of the drugs most
      commonly used by older people, many have potential to interact adversely with
      alcohol. The absorption, distribution, metabolism, and effects of drugs or
      alcohol may be affected. The major adverse clinical outcomes of drug-alcohol
      interactions are altered blood levels of the medication or of alcohol, liver
      toxicity, gastrointestinal inflammation and bleeding, sedation and delirium,
      disulfiram-like reactions, and interference with the desired effect of
      medications. Since alcohol is commonly used by elderly people, educating patients
      about the potential for these interactions should be a routine part of health
      care visits.

PMID- 8751324
TI  - The elderly and the use of illicit drugs: sociological and epidemiological
      considerations.
AB  - Debates over the prevalence of elderly illicit drug addicts in the population
      divert our attention from this group as a viable study population. Due to their
      decelerated lifestyle, low crime rates, and our attitudes toward the elderly as
      nonstreet drug users, they are likely to remain hidden from the public eye. This
      paper reviews past trends in drug misuse among the elderly, the lifestyle of
      those addicted to drugs, the complications associated with drug misuse and aging,
      and the problems that the elderly face with traditional treatment programs. Given
      our aging society, is the study of elderly street addicts and users an important
      area of concern?

PMID- 8751325
TI  - Alcohol and drug misuse in the nursing home.
AB  - The misuse of alcohol or drugs is a common and frequently neglected problem among
      nursing home residents. The misuse of prescription medications is particularly
      prevalent, but tobacco, alcohol, and illicit drugs are all subject of misuse by
      nursing home residents. This article reviews the epidemiologic and clinical
      aspects of substance misuse in nursing homes, including alcohol, illicit drugs,
      tobacco, and pyscho-active medications. Regulations regarding the prescription of
      psycho-active drugs in nursing homes is also discussed.

PMID- 8751326
TI  - Alcohol use, drug use, and well-being in older adults in Toronto.
AB  - This paper reports a study of alcohol- and drug-use by older clients in relation
      to their health and well-being. The sample of 349 persons was drawn from adults
      aged 60 and over living in senior citizens apartments in Toronto. Interviews were
      done in several languages. The results indicated that males and those aged 60 to
      65 were less happy and healthy, had fewer social supports, and more alcohol
      related problems. Drug-related problems were less numerous but occurred equally
      for both sexes. These results indicate that new alcohol programs are needed for
      the elderly, and these should focus on males, especially the younger elderly in
      transition from work to retirement.

PMID- 8751327
TI  - Immunolocalization of dehydroepiandrosterone sulfotransferase in normal and
      pathologic human adrenal gland.
AB  - Dehydroepiandrosterone sulfotransferase (DHEA-ST) catalyzes the conversion of
      dehydroepiandrosterone (DHEA) to dehydroepiandrosterone sulfate (DHEA-S) in the
      adrenals. Both DHEA and DHEA-S are quantitatively the most important
      corticosteroids in human. In this study, DHEA-ST was immunolocalized in normal (5
      cases) and neoplastic human adrenal glands (33 cases), using a specific IgG
      fraction raised against the enzyme. DHEA-ST was present in almost all the zona
      reticularis cells and some cortical cells demonstrating lipid depletion in the
      zona fasciculata but not in the zona glomerulosa of the normal adrenal. This
      finding is consistent with adrenocorticotrophic hormone dependency of the enzyme
      expression. In adrenocortical adenoma, DHEA-ST immunoreactivity was observed in
      all the cases of Cushing's adenoma, adenoma associated with pre-Cushing's
      syndrome, nonfunctioning, hormonally inactive adenoma, and two of seven cases of
      aldosteronoma, but distribution of immunoreactivity was markedly heterogeneous
      among the adenoma cases. In attached non-neoplastic adrenal glands of the
      adenoma, intense and diffuse immunoreactivity was observed in the zona
      reticularis cells in all the cases of aldosteronoma and five of six of the
      nonfunctioning hormonally inactive adenoma, but DHEA-ST immunoreactivity was not
      observed or sporadic in the attached adrenal glands of Cushing's adenoma and
      adenoma with pre-Cushing's syndrome. These results in the attached adrenal gland
      may be correlated with decreased DHEA-ST expression due to autonomous neoplastic
      cortisol secretion and subsequent adrenocorticotrophic hormone suppression. In
      adrenocortical carcinoma, DHEA-ST was observed in all the cases, but the relative
      immunointensity of carcinoma cells was weak compared to that of the zona
      reticularis of the normal adrenal and adenoma.

PMID- 8751328
TI  - Estrogen and progesterone receptors and anti-gross cystic disease fluid protein
      15 (BRST-2) fail to distinguish metastatic breast carcinoma from eccrine
      neoplasms.
AB  - Cutaneous metastases of breast carcinoma can be histologically similar to primary
      skin tumors with eccrine differentiation. We compared the immunohistochemical
      staining characteristics of 15 metastatic breast carcinoma skin lesions in 12
      patients to those of a series of primary eccrine tumors using estrogen receptor,
      progesterone receptor, and anti-gross cystic disease fluid protein-15 markers.
      Anti-gross cystic disease fluid protein-15 positivity was noted in 7 of 15 breast
      carcinoma skin metastases, 0 of 5 benign eccrine tumors, 1 of 6 microcystic
      adnexal carcinomas, and 1 of 1 metastatic sweat gland adenocarcinoma. Estrogen
      receptor positivity was found in 1 of 15 metastatic breast carcinoma skin
      lesions, 0 of 5 benign eccrine tumors, 2 of 8 microcystic adnexal carcinomas, and
      1 of 1 metastatic sweat gland adenocarcinoma. Progesterone receptor positivity
      was identified in 15 of 15 metastatic breast carcinoma skin lesions, 2 of 5
      benign eccrine tumors, 5 of 8 microcystic adnexal carcinomas, and 1 of 1
      metastatic sweat gland adenocarcinomas. These results indicate that standard
      immunohistochemical staining for estrogen receptors, progesterone receptors, and
      gross cystic fluid protein-15 markers will not reliably distinguish primary (or
      metastatic) eccrine tumors from cutaneous metastases of breast carcinoma.

PMID- 8751329
TI  - Multifocal micronodular pneumocyte hyperplasia: a distinctive pulmonary
      manifestation of tuberous sclerosis.
AB  - We report a peculiar multifocal micronodular proliferation of pneumocytes
      occurring in a 24-yr-old woman with tuberous sclerosis and
      lymphangioleiomyomatosis. A computed tomographic scan of the chest demonstrated
      multiple minute nodules present throughout both lung fields. Histologically, the
      nodules were well demarcated, measured up to 1.6 mm in diameter, and were
      composed of thickened, fibrotic, alveolar septa lined by pleomorphic, type II
      pneumocytes. Positive immunohistochemical stains for keratin, BER-EP4, and
      surfactant, and negative immunohistochemical staining with an antibody
      recognizing Clara cells support an epithelial origin from type II pneumocytes.
      The absence of immunohistochemical staining for HMB45 suggests a histogenesis
      separate than the lesions of lymphangioleiomyomatosis. We failed to detect
      estrogen or progesterone receptors in either the lesions of
      lymphangioleiomyomatosis or the micronodular proliferations. Recognition of these
      unique lesions facilitates their distinction from other epithelial
      proliferations, particularly atypical bronchioloalveolar cell hyperplasia. This
      lesion appears to be a distinctive manifestation of tuberous sclerosis. It is
      probably hamartomatous.

PMID- 8751330
TI  - p53, retinoblastoma gene product, and cyclin protein expression in human
      papillomavirus virus DNA-positive cervical intraepithelial neoplasia and invasive
      cancer.
AB  - Human papillomavirus interacts with cyclin protein and tumor suppressor genes,
      p53, and retinoblastoma gene (Rb). Expression of these gene products was examined
      in 69 formalin-fixed, paraffin-embedded cervical biopsies by immunohistochemistry
      utilizing antibodies against p53, Rb, and proliferating cell nuclear antigen
      (PCNA) and by human papillomavirus DNA in-situ hybridization assays. Samples
      selected for this study included 27 normal/reactive atypia cases that were all
      human papillomavirus DNA in-situ hybridization negative, 37 cervical
      intraepithelial neoplasia (CIN) lesions, and 5 invasive carcinomas. The CIN and
      invasive carcinoma cases were all human papillomavirus DNA in-situ hybridization
      positive. p53 protein expression was detected in approximately one-third of the
      reactive atypia and CIN lesions and in 60% of invasive cancers. Neither the
      amount or the location of p53 staining was correlated with the histologic
      diagnosis. Rb staining was more frequently found in the CIN/invasive carcinoma
      cases compared to the normal/reactive atypia samples (39/42 [93%] versus 21/27
      [78%], respectively; P < 0.05 by chi 2. PCNA staining was detected in virtually
      all samples tested. However, the location of both PCNA and Rb staining differed
      when the normal/reactive atypia cases were compared to the CIN cases. Only 10% of
      the former group demonstrated Rb staining throughout the basal two-thirds layer
      or full thickness of the epithelium compared with 65% of the latter group (P <
      0.001 by chi2). Likewise, PCNA staining of the basal two-thirds or full-thickness
      of the epithelium was found in only 58% of normal/reactive atypia cases, but in
      97% of the CIN group (P < 0.001). Our results suggest that the location of Rb and
      PCNA staining is quite different between normal/reactive atypia cervical biopsies
      and CIN lesions.

PMID- 8751331
TI  - Congenital cystic adenomatoid malformation of the lung: insights into the
      pathogenesis utilizing quantitative analysis of vascular marker CD34 (QBEND-10)
      and cell proliferation marker MIB-1.
AB  - Congenital cystic adenomatoid malformation (CCAM) encompasses a spectrum of
      variably cystic developmental anomalies of the lung histologically characterized
      by immature lung tissue. The pathogenesis is uncertain, but many investigators
      favor a maturation arrest in bronchopulmonary development. To investigate this
      hypothesis, the vascular development and proliferation capacity of lung tissue
      with CCAM type I from nine infants ranging in age from 20 weeks gestation to 42
      days old were studied immunohistochemically utilizing CD34 for the former and MIB
      1 for the latter. Both markers were quantitated on an image analysis system. CCAM
      was hypovascular with a mean vascular index of 20.05% +/- 6.58 compared to 40.06%
      +/- 4.19 for the age-matched controls (P < 0.000001). The proliferation index of
      both epithelial and mesenchymal components was higher in CCAM (10.46 +/- 3.48)
      than in control tissue (7.14 +/- 1.88; P < 0.012). In contrast to the control
      lung tissue which showed a remarkable synchrony between the vascular development
      and proliferation throughout the parenchyma, focal asynchrony between the
      proliferation of the epithelial and stromal components was noted in CCAM. The
      vascularity in CCAM corresponds to that seen in early gestation. The cellular
      proliferation in CCAM is higher than in full-term infants and corresponds to late
      second trimester or early third trimester fetuses. These findings support the
      proposed pathogenesis of a maturation defect in lung embryogenesis.

PMID- 8751332
TI  - Immunohistochemical analysis of p53 mutations in bronchioloalveolar carcinoma and
      conventional pulmonary adenocarcinoma.
AB  - Mutations of p53 tumor suppressor gene have been shown to contribute to
      tumorigenesis in a variety of human cancers. Normally, p53 protein degrades
      rapidly and is not detected by immunohistochemical procedure, but mutant p53 and
      wild-type p53 stabilized by certain viral oncoproteins can accumulate to
      immunohistochemically demonstrable levels. Conventional pulmonary adenocarcinomas
      and bronchioalveolar carcinomas, although morphologically similar, exhibit
      different biological behavior and clinical prognosis. To explore the differences
      in the expression of p53 protein in these two tumor types, we performed
      immunohistochemistry on 10 conventional pulmonary adenocarcinomas and 12
      bronchioalveolar carcinomas on formalin-fixed and paraffin-embedded material,
      using the commercially available monoclonal antibody against the mutant p53
      protein. Intense nuclear staining was observed in 80% (8/10) of conventional
      pulmonary adenocarcinomas, whereas all 12 bronchioalveolar carcinomas were
      negative for p53 protein. These observations indicate that altered p53 protein
      (probably mutant) is overexpressed in conventional adenocarcinomas and may be
      involved in its tumorigenesis or progression. On the other hand, the lack of p53
      expression in bronchioalveolar carcinomas suggests that an alternative pathway is
      likely to be responsible for its tumorigenesis. Furthermore, p53 protein
      immunostaining may be useful as an adjunct in differentiating conventional
      pulmonary adenocarcinomas from bronchioalveolar carcinomas.

PMID- 8751333
TI  - Demonstration of Chlamydia trachomatis in inguinal lymphadenitis of
      lymphogranuloma venereum: a light microscopy, electron microscopy and polymerase
      chain reaction study.
AB  - Intravacuolar organisms in vacuolated macrophages were associated with areas of
      necrosis and suppuration in 12 patients with suppurative inguinal lymphadenitis.
      The intravacuolar organisms measured 0.2 to 2.0 micrometers in diameter, stained
      Gram negative with the Brown-Hopp's tissue Gram stain, faintly blue with
      hematoxylin and eosin stain, and black with the Warthin-Starry silver
      impregnation stain. The organisms lined vacuolar membranes and/or clumped in
      centers of vacuoles. Electron microscopy revealed elementary and reticulate
      bodies and intermediate forms characteristic of the genus Chlamydia. Cultures of
      three lymph nodes in McCoy cells grew Chlamydia trachomatis, lymphogranuloma
      venereum (LGV) serovars. Polymerase chain reaction using primers for chlamydial
      16S ribosomal DNA confirmed the organisms as Chlamydia in lymph nodes from nine
      patients. Recognition of chlamydial organisms by light microscopy in tissue
      sections of lymph nodes allows a definitive diagnosis of lymphogranuloma
      venereum.

PMID- 8751334
TI  - Recent advances in the pathology of ovarian tumors.

PMID- 8751335
TI  - Design of a new disposable ERG electrode.
AB  - A new electrode for electroretinography (ERG) has been produced. The new device
      made of gold filament was applied as corneal and noncorneal electrod. Flash ERG
      and pattern ERG were recorded in normal subjects using this new electrode and
      compared with those made by available electrodes. There were so significant
      differences in amplitude and latency between the new electrode placed on the
      cornea and the JET-type electrode. For pattern ERG there were no significant
      differences between the new electrode placed in the lower fornix and a gold-foil
      type electrode. As this new electrode is less expensive and more comfortable than
      the available electrodes, it is clinically useful.

PMID- 8751336
TI  - Visaline in the treatment of age-related macular degeneration: a pilot study.
AB  - Age-related macular degeneration (AMD) is the main cause of a reduction in visual
      acuity in patients over the age of 65 years. A positive influence of medical
      treatment (i.e. with vitamins and trace minerals) has been suggested but remains
      unproven. In this randomized, double-blind study, 20 patients in an early stage
      of AMD were included. Over a period of 6 months, 9 patients were treated with
      Visaline and 11 with a placebo. The effect of the treatment was not statistically
      different between the two groups, admittedly small in number, in terms of visual
      and retinal acuity, color vision, and contrast sensitivity. Despite the lack of
      such measureable differences, the patients' own subjective assessments, however,
      were much better in the Visaline-treated group. Due to the short duration of the
      observation time, we can not comment on a possible long-term effect.

PMID- 8751337
TI  - Experimental tolerance to perfluorodecalin used in prolonged intraocular
      tamponade.
AB  - The authors report the results of an experimental study of a series of 16 rabbit
      eyes that underwent prolonged tamponade by a liquid perfluorocarbon (LPFC). After
      vitreous compression by C3F8, a complete gas/LPFC exchange is performed and left
      in place for 48 h, 12 days and 21 days. Study of the retina by light and electron
      microscopy showed numerous lesions: vacuolization in the nerve fiber layer,
      progressive defects of the outer photoreceptor segments and presence of
      pseudomyelinic bodies in the inner plexiform layer. The axonal fiber loss is
      shown by a specific marker. The analysis of the results underlines the mechanical
      toxicity of LPFCs used in prolonged tamponade, which are too heavy for the
      neurosensory retina.

PMID- 8751338
TI  - Ocular infections: antibiotics and bacterial adhesion on biomaterials used in
      ocular surgery.
AB  - The in vitro antibacterial activity of ofloxacin, sagamycin and other antibiotics
      was evaluated against 85 bacterial isolates [coagulase-negative staphylococci
      (CNS), n = 37, Staphylococcus aureus, n = 28, and Pseudomonas aeruginosa, n = 20]
      obtained from patients with ocular infections. The antistaphylococcal activity of
      ofloxacin was quite elevated with a 90% minimal inhibitory concentration (MIC90)
      of 1.56 mg/l against CNS and S. aureus. Rokitamycin and erythromycin showed a
      good activity against methicillin-sensitive staphylococci, but were less active
      than ofloxacin and sagamycin against methicillin-resistant strains (MIC90 > 100
      mg/l). Sagamycin was highly effective against staphylococci (MIC90 0.78 mg/l) and
      appeared to be the most active compound against P. aeruginosa (MIC90 6.25 mg/l),
      followed by ofloxacin, tobramycin and gentamicin. In a successive part of the
      study, the adhesive properties of slime-producing staphylococci were tested on
      biomaterials used in ocular surgery. Intraocular lenses, Silastic sheetings,
      circling bands and grooved strips showed a high affinity for slime-producing
      strains, while round silicone sponges were not covered by bacterial biofilm. In
      the last part of our study, we demonstrated how subMIC levels of ofloxacin
      increased the adhesion of slime-producing staphylococci. Our data confirmed the
      excellent activity of ofloxacin and sagamycin against ocular pathogens and the
      key role of adhesion in promoting colonization and infections of biomaterials.

PMID- 8751339
TI  - Modification of the scleral openings to reduce tissue breakdown and exposure
      after hydroxyapatite implantations.
AB  - We compared the incidence of exposure of the hydroxyapatite implant after
      evisceration according to the position of scleral windows which allow rapid
      fibrovascularization into the implant. Three patients (10%) developed tissue
      breakdown and exposure of the hydroxyapatite, out of 30 patients who had external
      scleral windows located in a position just anterior to the insertion of each of
      the rectus muscles, whereas no patient developed exposure, out of 24 patients who
      had internal scleral windows located in a position just position just posterior
      to the insertion of each of the rectus muscles. Internal windows sealed with
      rectus muscles could prevent direct contact between implant and the overlying
      Tenon's capsule and conjunctiva. These findings seem to indicate that the rough
      spicular surface of the hydroxyapatite irritates and erodes the overlying Tenon's
      capsule and conjunctiva.

PMID- 8751340
TI  - Visual acuity after scleral buckling surgery.
AB  - We reviewed 745 cases of retinal detachment which had been successfully treated
      by scleral buckling and had presented without preoperative ocular problems
      precluding visual recovery. Final visual acuity (VA) was 0.5 or better in 517
      cases (69.4%). The main causes of final VA below 0.5 were photoreceptor
      dysfunction, macular pucker, cystoid macular edema, and intraoperative
      retrofoveal hemorrhage. Stepwise logistic regression analysis revealed that five
      variables predicted visual failure: patient's age of 71 years or more;
      preoperative VA reduced either to light perception counting fingers or to 0.1
      0.4; low or high macular detachment for more than 7 days; grade B preoperative
      proliferative vitreoretinopathy, and intraoperative hemorrhage.

PMID- 8751341
TI  - Keratitis solaris and sunbeds.
AB  - Keratitis solaris is caused by ultraviolet radiation in the range 200-320 nm. The
      threshold dose for keratitis solaris is 40 J/m2 for short-term exposure. We
      measured the emission spectra of 22 sunbeds in the range 250-500 nm with a high
      resolution double monochromator and calculated the exposure times for the
      threshold dose of keratitis solaris. Depending on the type of lamp used, the
      exposure times ranged from 90 s to 3.5 h. Lamps with short exposure times for
      keratitis solaris can induce keratitis solaris if protective goggles are not used
      (e.g., to achieve a uniform tan of the eye area) and if the eyes are opened
      briefly several times, perhaps, to look at a watch. Generally, sunbed users have
      no way of ascertaining the lamp type or its emission spectrum and of determining
      the exposure time for the threshold dose of keratitis solaris.

PMID- 8751342
TI  - Primary intraocular lymphoma mimicking late postoperative endophthalmitis.
AB  - We treated a 65-year old woman with diffuse uveitis and an intraocular mass. The
      diffuse uveitis resolved with the administration of corticosteroids, but the
      intraocular mass did not respond to treatment. A transscleral biopsy of the
      lesion was performed. Histopathological study revealed non-Hodgkin's large-cell
      lymphoma. Immunohistochemical analysis showed that the tumor cells were derived
      from B-cells. The intraocular mass diminished after radiation therapy. The
      transscleral biopsy proved useful in establishing the correct diagnosis.

PMID- 8751343
TI  - Early clinical and ultrastructural effects of diltiazem injection on rabbit
      extraocular muscles.
AB  - We injected diltiazem into the left lateral rectus muscles (LR) of 10 rabbits in
      order to examine the ultrastructural effects of diltiazem on rabbit extraocular
      muscles and estimate its advantages in clinical use as an alternative to the
      surgical therapy of strabismus. The animals were divided into two groups
      according to the time of evaluation following the injection. The LR muscles of
      both eyes of the first group were respected 60 min after the injection, for
      ultrastructural examination. The same procedure was done for the second group at
      the 24th hour. The right eyes were used as the control group. There was a medial
      shift 3-5 min following the injection in the left eyes of both groups. The
      ultrastructural examination revealed weakness in muscle contractility, probably
      as a result of inhibition of glycogen usage due to calcium accumulation. In this
      study, we examined the early clinical and ultrastructural effects of diltiazem.

PMID- 8751344
TI  - Effects of the passive transfer of anti-gB antibodies in a rabbit model of HSV-1
      induced keratitis.
AB  - The effectiveness of passively transferred antibodies directed against the
      secretory form of herpes simplex virus type 1 (HSV-1) glycoprotein B (gB1-s) was
      tested in a rabbit model of ocular HSV-1 infection. The animals were passively
      immunized through the intramuscular injection of a homologous polyclonal anti-gB1
      s antiserum at different times from the viral ocular challenge (i.e. at -24, 0,
      +24 and +48 h from infection). The effects observed in this trial were compared
      with those obtained in an active immunization trial, in which the animals were
      vaccinated with gB1-s before the ocular infection with HSV-1 (large variant). The
      results have shown that passive immunization appears quite effective in
      prophylactic utilization, whereas it is less effective when performed at 24 or 48
      h after inoculation. By contrast, active immunization of rabbits proved to be
      highly effective both in preventing the development of fatal encephalitis and in
      reducing the severity of corneal lesions.

PMID- 8751345
TI  - Anterior ischemic optic neuropathy associated with pulseless disease.
AB  - A 41-year-old man with pulseless disease presented with a sudden onset of visual
      loss in the right eye. The right fundus showed moderate optic disk swelling with
      mild pallor. Aortography demonstrated bilateral obstruction of the common carotid
      arteries and left subclavian artery, and only collateral vessels supplied the
      upper portion. Temporal artery biopsy revealed no inflammation. In addition, the
      patient originally had relatively small disks. This anatomical factor and marked
      hypoperfusion of the posterior ciliary artery presumably caused nonarteritic
      anterior ischemic neuropathy in this patient.

PMID- 8751346
TI  - Isolation and purification of plant nucleic acids. Genomic and chloroplast DNA.

PMID- 8751347
TI  - Isolation and purification of insect DNA.

PMID- 8751348
TI  - Isolation and purification of vertebrate DNAs.

PMID- 8751349
TI  - Statistical analysis of arbitrarily primed PCR patterns in molecular taxonomic
      studies.

PMID- 8751350
TI  - Molecular identification of phytopathogenic viruses.

PMID- 8751351
TI  - Improved PCR methods for identification of phytopathogenic viruses.

PMID- 8751352
TI  - PCR detection of HIV.

PMID- 8751353
TI  - The use of consensus PCR and direct sequence analysis for the identification of
      HPV.

PMID- 8751354
TI  - The identification of dengue virus using PCR.

PMID- 8751355
TI  - The design and application of ribosomal RNA-targeted, fluorescent oligonucleotide
      probes for the identification of endosymbionts in protozoa.

PMID- 8751356
TI  - Subtraction hybridization for the isolation of strain-specific Rhizobium DNA
      probes.

PMID- 8751357
TI  - The use of RAPD for generating specific DNA probes for microorganisms.

PMID- 8751358
TI  - ITS-RFLP matching for identification of fungi.

PMID- 8751359
TI  - Specific PCR primers for the identification of endomycorrhizal fungi.

PMID- 8751360
TI  - Single-strand conformational polymorphism (SSCP) for the identification of
      endomycorrhizal fungi.

PMID- 8751361
TI  - The use of RAPD for isolate identification of arbuscular mycorrhizal fungi.

PMID- 8751362
TI  - Establishing relationships between closely related species using total genomic
      DNA as a probe.

PMID- 8751363
TI  - Detection and characterization of Leishmania parasites by DNA-based methods.
      Southern blotting and PCR.

PMID- 8751364
TI  - The molecular identification of trypanosomes.

PMID- 8751365
TI  - Detection and identification of the four malaria parasite species infecting
      humans by PCR amplification.

PMID- 8751366
TI  - The use of degenerate primers in conjunction with strain and species
      oligonucleotides to classify Onchocerca volvulus.

PMID- 8751367
TI  - The use of synthetic DNA probes for the field identification of members of the
      Anopheles gambiae complex.

PMID- 8751368
TI  - PCR of the ribosomal DNA intergenic spacer regions as a method for identifying
      mosquitoes in the Anopheles gambiae complex.

PMID- 8751369
TI  - Restriction fragment length polymorphism (RFLP) analyses. Distinguishing African
      and European honey bees.

PMID- 8751370
TI  - Differential screening for the isolation of species-specific sequences in the
      Anopheles farauti complex.

PMID- 8751371
TI  - RAPD-PCR with parasitic hymenoptera.

PMID- 8751372
TI  - The use of selective enrichment for the isolation of species-specific DNA probes
      for insects.

PMID- 8751373
TI  - Report and abstracts of the Fourth International Workshop on Human Chromosome 2
      Mapping 1996.

PMID- 8751374
TI  - The RNA polymerase I transcription factor UBF and rDNA are located at the same
      major sites in both interphase and mitotic pig embryonic kidney (PK) cells.
AB  - Indirect immunolabeling with anti-UBF antibodies, in situ hybridization with an
      rDNA probe, and confocal scanning laser microscopy were used to study nucleolar
      organizer regions (NORs) during the cell cycle in pig embryonic kidney (PK)
      cells. The chromosomal distribution of the polymerase I transcription factor UBF
      and rDNA was compared with the number of silver-stained NORs (Ag-NORs) present
      and nucleolar size. It was shown, both at interphase and mitosis, that the
      majority of UBF and rDNA signals were located at the same foci and that the
      amounts of UBF and rDNA at any given site were in a striking positive
      correlation. At mitosis, only the NORs were labeled; at interphase, the signals
      for both UBF and rDNA were arranged in necklace-like structures around the
      nucleoli. No chromosomal NORs without Ag-proteins or UBF were present, indicating
      that all NORs in PK cells are active at interphase. It was concluded that (1) UBF
      and rDNA co-localize throughout the cell cycle in PK cells; (2) their association
      with mitotic NORs is determined by the number of rDNA repeats, rather than by any
      differential ability of NORs to recruit the transcription factor; and (3) the
      amount of UBF can be correlated with the size and activity of the nucleoli at
      interphase.

PMID- 8751375
TI  - Structure and chromosomal assignment of the murine sterol carrier protein 2 gene
      (Scp2) and two related pseudogenes by in situ hybridization.
AB  - The murine sterol carrier protein 2 gene (Scp2) has been mapped to chromosome 4C5
      ->D1 by in situ hybridization. This location is syntenic with the locus of SCP2
      on human chromosome 1p32. We found the overall structure of murine Scp2 to be
      identical to that of the human SCP2 gene. In addition, two Scp2 pseudogenes have
      been isolated and mapped to chromosomes 3H2-->4 and 9F.

PMID- 8751376
TI  - Sex-linkage of glucosephosphate isomerase-B and mapping of the sex-determining
      gene in channel catfish.
AB  - Sex-linkage of glucosephosphate isomerase-B (GPI-B) was observed in five
      experimental matings between heterozygous male and homozygous female channel
      catfish (Ictalurus punctatus). Offspring phenotypes for GPI-B were 40.8%
      heterozygous male and 43.0% homozygous female, while recombinant offspring were
      7.4% homozygous male and 8.8% heterozygous female. Thus, GPI-B and the sex
      determining gene (SDG) were linked and had a recombination rate of 16.2%. This
      linkage was designated I. punctatus linkage group XXIX. The gene-centromere
      distance (1.66 cM) of SDG, estimated in six gynogenetic families derived from XY
      females, indicated that SDG resides very close to the centromere. Based on
      estimates of these genetic distances, a chromosomal order of GPI-B-centromere-SDG
      was proposed. Additionally, joint segregation of GPI-A and SDG in two
      experimental matings indicated no genetic linkage between GPI-A and sex. These
      genetic relationships were compared to those reported in other teleost taxa with
      regard to evolutionary conservation of ancestral gene arrangements.

PMID- 8751377
TI  - Genetic mapping of the mouse stromal cell-derived factor gene (Sdf1) to mouse and
      rat chromosomes.
AB  - Stromal cell-derived factor 1 (SDF1) is a new member of the Cys-X-Cys chemokine
      family. The chromosomal location of Sdf1, the gene coding mouse SDF1, was
      determined by fluorescence in situ hybridization (FISH) and molecular linkage
      analysis. The mouse Sdf1 gene was localized to the R-band-positive F1 band of
      chromosome 6 by direct R-banding FISH. Interspecific backcross analysis
      identified the mouse Sdf1 gene locus at 0.8 cM terminal to D6Nit55 and 3.0 cM
      proximal to D6Mit12. With in situ hybridization using a mouse cDNA clone as a
      probe, the rat Sdf1 gene was localized to the R-band-positive band 4q42.1, where
      conserved linkage homology to mouse chromosome 6 has been identified. Although
      other Cys-X-Cys chemokine genes have been mapped on human chromosome 4, the
      chromosomal segment where the mouse and rat Sdf1 gene reside have no conserved
      linkage homology to human chromosome 4. This result suggests that SDF1 is a new
      chemokine class.

PMID- 8751378
TI  - Localization of ribosomal genes in human spermatogonia by fluorescent in situ
      hybridization and confocal microscopy.
AB  - The distribution of ribosomal RNA genes in nucleoli is still a matter of
      controversy. We have investigated the nucleolus of human type A spermatogonia,
      which displays a single, large fibrillar center. Silver-staining was used to
      localize the fibrillar center by light microscopy. Fluorescent in situ
      hybridization was performed on the same cell, using a 5.8-kb probe specific for a
      transcribed region of the ribosomal genes. The fluorescent area exactly
      corresponded to the silver-stained area. The three-dimensional distribution of
      rDNA was studied in horizontal and orthogonal sections using a confocal laser
      scanning microscope. The presence of the fluorescent signal throughout the whole
      silver-stained structure demonstrated that the fibrillar center, and at least a
      part of the dense fibrillar component, contained most of the rDNA.

PMID- 8751379
TI  - Assignment of GRSF1 encoding a poly(A)+ mRNA binding protein to human chromosome
      4q13.

PMID- 8751380
TI  - Localization of the human gene encoding the 13.3-kDa subunit of mitochondrial
      complex III (UQCRB) to 8q22 by in situ hybridization.
AB  - We have localized the human gene encoding the 13.3-kDa subunit of mitochondrial
      complex III (UQCRB) to chromosome 8 using both radioactive in situ hybridization
      and fluorescence in situ hybridization. The additional peak obtained with the
      former method is attributed to the higher sensitivity of this technique, which
      results in hybridization of the probe to the less conserved pseudogene. We
      therefore conclude that the functional gene is most likely located at 8q22.

PMID- 8751381
TI  - Double and triple in situ chromosomal labeling of human spermatozoa by PRINS.
AB  - The PRimed IN Situ (PRINS) labeling method allows rapid, specific detection of
      human chromosomes in situ. We have adapted the PRINS protocol to mature human
      sperm in combination with a 3 M NaOH protocol for simultaneous in situ
      decondensation and denaturation of sperm nuclei. Using fluorochrome-labeled dNTPs
      in a sequential PRINS reaction, the direct detection of two or three distinct
      chromosomes must be performed within a timespan of 3 h. The method was tested
      with primers specific for chromosomes 8, 9, 12, 13, 16, 18, and 21 and the X. The
      frequencies of disomy ranged from 0.11% to 0.34%. Chromosome-specific primers
      have been defined for most of the human chromosomes, including some that are
      indistinguishable by fluorescence in situ hybridization (FISH) with centromeric
      probes. Consequently, this new strategy constitutes a rapid and efficient
      alternative to FISH for detecting nondisjunction in human sperm.

PMID- 8751382
TI  - Genetic linkage mapping of the human steroid 5 alpha-reductase type 2 gene
      (SRD5A2) close to D2S352 on chromosome region 2p23-->p22.
AB  - Two steroid 5 alpha-reductase isoenzymes catalyze the conversion of testosterone
      into dihydrotestosterone, the more bioactive androgen, which is essential for
      male phenotypic sexual differentiation and for androgen-mediated growth of such
      tissues and organs as the prostate. Inherited mutations in SRD5A2 cause male
      pseudohermaphroditism. The SRD5A1 and SRD5A2 genes encoding the steroid 5 alpha
      reductase type 1 and type 2 isoenzymes have been previously assigned by in situ
      hybridization to 5p15 and 2p23, respectively. To map the SRD5A2 gene by linkage
      analysis, a novel RsaI RFLP detected in exon I and a TA repeat polymorphism found
      in exon V were genotyped in eight CEPH reference families. A two-point linkage
      analysis was performed between these polymorphisms and the chromosome 2
      microsatellite markers of Genethon and NIH/CEPH. The closest linkage was observed
      with D2S352 (Zmax = 24.06; thetamax = 0.001) in the region 2p23-->p22. To further
      define the localization of SRD5A2, a framework map, including nine Genethon
      markers flanking the polymorphic SRD5A2 locus, was built by multipoint linkage
      analysis. This led to a high-resolution genetic map of the region flanking the
      polymorphic SRD5A2 gene, including the nine Genethon markers and three NIH/CEPH
      markers, yielded the following order: tel-D2S48-D2S149-D2S320-D2S171-D2S165-
      [D2S352/SRD5A2]-D2S367-[D2S19/D2S177]-[ D2S391/CALM]-D2S378-cen.

PMID- 8751383
TI  - M32, a murine homologue of Drosophila heterochromatin protein 1 (HP1), localises
      to euchromatin within interphase nuclei and is largely excluded from constitutive
      heterochromatin.
AB  - Mice possess two structural homologues of Drosophila HP1, termed M31 and M32
      (Singh et al., 1991). We have previously shown that an M31-specific monoclonal
      antibody (MoAb), MAC 353, localises to constitutive heterochromatin (Wreggett et
      al., 1994). Here we report that a MoAb raised against the M32 protein (MAC 385)
      recognises a 22-kDa protein in murine nuclear extracts and that M32 is
      distributed in a fine-grain "speckled" pattern within interphase nuclei. M32 is
      also largely excluded from the large masses of constitutive heterochromatin that
      are labelled by MAC 353.

PMID- 8751384
TI  - Genomic cloning and localization to chromosome 11p15.5 of the human achaete-scute
      homolog 2 (ASCL2).
AB  - The mouse achaete-scute homolog-2 gene (Mash2), a member of the achaete-scute
      gene family, encodes a transcription factor that plays an important role in the
      development of the trophoblast. It has recently been reported that Mash2 is
      genomically imprinted and mapped to the distal region of mouse chromosome 7,
      where other imprinted genes, Ins2, Igf2 and H19 are located. We isolated a clone
      carrying the partial human homolog, ASCL2, from a human genomic phage library
      using a PCR product for the rat Ascl2-cDNA as a probe. By fluorescence in situ
      hybridization using a phage clone as a probe whose insert contained the partial
      human ASCL2, we assigned ASCL2 to human chromosome 11p15.5. Sequence comparisons
      of the human ASCL2 clone and the rat Ascl2-cDNA showed 86.9% identity spanning
      206 nucleotides and 85.3% deduced polypeptide-sequence identity over 68 residues.

PMID- 8751385
TI  - Identification and assignment of a new gene (D20S756) to human chromosome 20p13.

PMID- 8751386
TI  - Coding sequence and chromosome mapping of the human gene (CDC46) for replication
      protein hCdc46/Mcm5.
AB  - We have isolated the complete cDNA sequence encoding the human homolog of the
      yeast replication protein Cdc46/Mcm5. The cDNA was used as a probe for
      chromosomal fluorescence in situ hybridization (FISH), which localized the human
      Cdc46 gene (CDC46) to chromosome region 22q13.1-->q13.2. This is the fourth human
      Mcm gene whose chromosome region has been determined, and it is now apparent that
      human Mcm genes are widely distributed in the genome. As deduced from the cDNA
      sequence, human protein hCdc46 is composed of 734 amino acids and contains a
      central region that is almost 80% identical with the yeast protein.
      Immunoprecipitation experiments with hCdc46-specific antibodies confirm that
      essentially all nuclear hCdc46 proteins form a stable dimeric complex with
      protein P1Mcm3.

PMID- 8751387
TI  - Fluorescent in situ hybridization on archival G-banded slides.
AB  - We report a simple procedure that allows the application of chromosomal in situ
      suppression hybridization to standard G-banded and Entellan-mounted archival
      preparations that had been stored for 4-8 y. The procedure includes removing the
      cover slips in xylene, refixation in buffered formaldehyde-acetone mixture, and
      washing in 2 x SSC, Tween 20.

PMID- 8751388
TI  - MDM2 amplification in a primary alveolar rhabdomyosarcoma displaying a
      t(2;13)(q35;q14).
AB  - This report describes a case of rhabdomyosarcoma associated with a 2;13
      translocation and multiple double minute chromosomes. The origin of the amplified
      DNA was identified using comparative genomic hybridization, which pinpointed a
      unique spot at 12q13-->q14. Band 12q13 has been shown to contain several genes
      that are occasionally amplified in other sarcomas. Fluorescene in situ
      hybridization to tumor metaphases with probes specific for this region indicated
      that the double minutes contained the MDM2 gene but not the CDK4 gene. MDM2
      amplification was further quantified by Southern hybridization, which showed a
      mean value of 25 copies per haploid genome. This is the first example of MDM2
      amplification in a rhabdomyosarcoma.

PMID- 8751389
TI  - Analysis of CA repeat polymorphisms places three human gene loci on the 8p
      linkage map.
AB  - The gene loci for luteinizing hormone-releasing hormone (LHRH), the beta-3
      adrenergic receptor (ADRB3), and heregulin (HGL) have been assigned to the short
      arm of human chromosome 8, but the positions of these loci on the human genetic
      linkage map have not been previously reported. We have isolated simple tandem
      repeat polymorphisms (STRPs) for these loci. These STRPs enabled us to determine
      the genetic map locations for these genes.

PMID- 8751390
TI  - Identification and mapping of type 1 neurofibromatosis (NF1) homologous loci.
AB  - During the establishment of a YAC contig for the type 1 neurofibromatosis (NF1)
      region on human chromosome 17q11.2, several YAC clones were isolated which
      originated from a different chromosome but which retained strong homology to NF1
      coding regions (Marchuk et al., 1992). Fluorescence in situ hybridization (FISH)
      using these clones has identified NF1-homologous loci on several human
      chromosomes, including 2, 14, 15, 21, and 22. PCR amplification using primers
      originally designed to amplify NF1 exons has confirmed these chromosome
      localizations and, in addition, has revealed NF1-homologous sequences on
      chromosomes 12 and 20. Sequence analysis of the amplified products has
      demonstrated that (1) most of these loci have > 90% identity with NF1 sequences;
      (2) most of these loci represent nonprocessed pseudogenes; and (3) for the
      chromosome 12 locus, the two described regions of homology with NF1 have open
      reading frames. Finally, we have identified two novel alpha-satellite DNA repeat
      units in proximity to NF1-homologous sequences on chromosome 14. Their
      association suggests a mechanism for dispersion of the NF1-homologous loci based
      on alpha-satellite-mediated exchange between nonhomologous chromosomes.

PMID- 8751391
TI  - Assignment of the membrane-associated modulator of the Na(+)-sugar cotransport
      systems gene RSC1A1 to human chromosome 1p36.1 by in situ hybridization.

PMID- 8751392
TI  - Point mutation analysis of archived cytogenetic slide DNA.
AB  - Archived Giemsa-stained cytogenetic slide repositories represent valuable DNA
      resources for medical, scientific, and forensic studies. Sequencing readily
      identified a Charcot-Marie-Tooth disease point mutation in a 209-bp PCR amplified
      product. With optimal PCR primers and amplification conditions, our protocol
      quickly and reliably isolated sufficient DNA for at least 12 independent PCR
      amplification reactions for forensic and medical applications from single slides
      up to 5 years old.

PMID- 8751393
TI  - Conformal technique dose escalation for prostate cancer: biochemical evidence of
      improved cancer control with higher doses in patients with pretreatment prostate
      specific antigen > or = 10 NG/ML.
AB  - PURPOSE: Conformal radiation technology results in fewer late complications and
      allows testing of the value of higher doses in prostate cancer. METHODS AND
      MATERIALS: We report the biochemical freedom from disease (bNED) rates (bNED
      failure is Prostate Specific Antigen (PSA) > or = 1.5 ng/ml and rising) at 2 and
      3 years for 375 consecutive patients treated with conformal technique from 66 to
      79 Gy. Median follow-up was 21 months. Biochemical freedom from disease was
      analyzed for patients treated above and below 71 Gy as well as above and below 73
      Gy. Each dose group was subdivided by pretreatment PSA level (< 10, 10-19.9, and
      > or = 20 ng/ml). Dose was stated to be at the center of the prostate gland.
      RESULTS: There was significant improvement in bNED survival for all patients
      divided by a dose above or below 71 Gy (p = 0.007) and a marginal improvement
      above or below 73 Gy (p = 0.07). Subdividing by pretreatment PSA level showed no
      benefit to the PSA < 10 ng/ml group at the higher dose but there was a
      significant improvement at 71 and 73 Gy for pretreatment PSA 10-19.9 ng/ml (p =
      0.03 and 0.05, respectively) and for pretreatment PSA > or = 20 ng/ml (p = 0.003
      and 0.02, respectively). CONCLUSIONS: Increasing dose above 71 or 73 Gy did not
      result in improved bNED survival for patients with pretreatment PSA < 10 ng/ml at
      2 or 3 years. Further dose escalation studies may not be useful in these
      patients. A significant improvement in bNED survival was noted for patients with
      pretreatment PSA > or = 10 ng/ml treated above 71 or 73 Gy; further dose
      escalation studies are warranted.

PMID- 8751394
TI  - A pilot survey of sexual function and quality of life following 3D conformal
      radiotherapy for clinically localized prostate cancer.
AB  - PURPOSE: To assess the impact of high dose three-dimensional conformal
      radiotherapy (3D CRT) for prostate cancer on the sexual function-related quality
      of life of patients and their partners. METHODS AND MATERIALS: Sixty of 124
      consecutive patients (median age 72.3 years) treated with 3D CRT for localized
      prostate cancer were surveyed and reported being potent prior to treatment. The
      answers to survey questions assessing the impact of quality of life related to
      sexual function from these 60 patients and their partners forms the basis for
      this retrospective analysis. RESULTS: Following 3D CRT, 37 of 60 patients (62%)
      retained sexual function sufficient for intercourse. Intercourse at least once
      per month was reduced from 71 to 40%, whereas intercourse less than once per year
      increased from 12 to 35%. Following treatment, 25% of patients reported that the
      change in sexual dysfunction negatively affected their relationship or resulted
      in poor self-esteem. This outcome was associated with impotence following
      treatment (p < 0.01). Patients who had partners and satisfactory sexual function
      appeared to be at a higher risk of having a negatively affected relationship or
      losing self-esteem if they become impotent (p < 0.05). Partners of patients who
      reported a negatively affected relationship or loss of self-esteem appear to be
      less likely to return the survey instrument used (p = 0.02). CONCLUSIONS: More
      work is needed to evaluate the impact of radiotherapy and other treatments on the
      quality of life of patients and their partners to allow adequate informed consent
      to be given.

PMID- 8751395
TI  - 103Pd brachytherapy and external beam irradiation for clinically localized, high
      risk prostatic carcinoma.
AB  - PURPOSE: To summarize biochemical failure rates and morbidity of external beam
      irradiation (EBRT) combined with palladium (103Pd) boost for clinically localized
      high-risk prostate carcinoma. METHODS AND MATERIALS: Seventy-three consecutive
      patients with stage T2a-T3 prostatic carcinoma were treated from 1991 through
      1994. Each patient had at least one of the following risk factors for
      extracapsular disease extension: Stage T2b or greater (71 patients), Gleason
      score 7-10 (40 patients), prostate specific antigen (PSA) > 15 (32 patients), or
      elevated prostatic acid phosphatase (PAP) (17 patients). Patients received 41 Gy
      EBRT to a limited pelvic field, followed 4 weeks later by a 103Pd boost
      (prescription dose: 80 Gy). Biochemical failure was defined as a PSA greater than
      1.0 ng/ml (normal < 4.0 ng/ml). Patients whose PSA was still decreasing at the
      last follow-up were censored at that time. Patients whose PSA plateaued at a
      value greater than 1.0 were scored as failures at the time the PSA first
      plateaued. RESULTS: The overall, actuarial freedom from biochemical failure at 3
      years after treatment was 79%. In Cox proportional hazard multivariate analysis,
      the strongest predictor of failure was elevated acid phosphatase (p = 0.04),
      followed by PSA (p = 0.17), Stage (p = 0.23), and Gleason score (p = 0.6).
      Treatment-related morbidity was usually limited to temporary, RTOG Grade 1-2
      urinary symptoms. One patient, who had both a transurethral incision of the
      prostate (TUIP) and a transurethral resection of the prostate (TURP), developed
      low-volume urinary incontinence. The actuarial potency rate at 3 years after
      implantation was 77% for 46 patients who were sexually potent prior to implant.
      CONCLUSION: Biochemical freedom from failure rates following combined EBRT and
      103Pd brachytherapy for clinically localized, high-risk prostate cancer compare
      favorably with that reported after conventional dose EBRT alone. Morbidity has
      been acceptable.

PMID- 8751397
TI  - Pretreatment p53 immunoreactivity does not infer radioresistance in prostate
      cancer patients.
AB  - PURPOSE: To test, in a clinical context, the hypothesis that p53 aberrations,
      assessed by immunoreactivity, are related to radioresistance as suggested by
      several experimental studies. METHODS AND MATERIALS: Sixty patients with prostate
      cancer who underwent transurethral resection of the prostate or biopsy prior to
      definitive external beam therapy were retrospectively identified. The endpoint in
      the study was cancer specific survival. The nuclear accumulation of the aberrant
      p53 protein was evaluated by immunohisto-chemistry with the pantropic, monoclonal
      Ab-6 anti-p53 antibody (clone DO-1) on pretreatment biopsies. Immunoreactivity
      was related to stage, grade, and cancer-specific survival. RESULTS: There was a
      correlation between p53 immunoreactivity and low tumor stage (p < 0.001), but no
      relation between p53 status and grade was found. Moreover, no significant
      difference was found in cancer-specific survival between the p53 positive tumors
      (109 months) and the p53 negative tumors (99 months). CONCLUSIONS: No
      disadvantage regarding survival was seen for patients with p53 immunoreactive
      tumors, implicating that p53 immunoreactivity does not infer radioresistance in
      prostate cancer. This suggests that the p53 inactivation may be a less important
      determinant of tumor response to radiotherapy in some human cancers than in the
      previously studied experimental situations. Thus, other mechanisms may be more
      important in determining outcome after radiation. However, the series is small
      and data should be interpreted with caution.

PMID- 8751398
TI  - Definitive radiotherapy for carcinoma of the vagina: outcome and prognostic
      factors.
AB  - PURPOSE: Primary carcinoma of the vagina is an uncommon tumor. Because of the
      long-standing interest in this disease at our institution a substantial number of
      patients with this disease has been accumulated, and this retrospective review
      was performed to define disease outcome, to delineate significant prognostic
      factors, and to provide treatment guidelines. METHODS AND MATERIALS: This was a
      retrospective review of 301 patients with vaginal carcinoma (271 with squamous
      cell and 30 with adenocarcinoma) who received definitive radiotherapy between
      1953 and 1991. Prognostic factors for outcome (local control, pelvic control,
      metastatic relapse, survival, and complications) were evaluated using univariate
      and multivariate techniques. RESULTS: Patients disease was staged using the
      International Federation of Gynecology and Obstetrics (FIGO) system, and stages
      were distributed as follows: 0, 37 (12%); I, 65 (22%); II, 122 (40%); III, 60
      (20%); and, IVA, 17 (6%). Treatment varied according to stage, with brachytherapy
      predominating for early disease but external beam playing a prominent role for
      more advanced disease. Patients with in situ disease received brachytherapy alone
      or transvaginal orthovoltage irradiation. For Stage I, brachytherapy alone was
      used in 25, external beam and brachytherapy in 38, and transvaginal alone in 2.
      For Stage II, brachytherapy alone was used in 20, external and brachytherapy in
      66, and external irradiation alone in 36. For Stage III, external and
      brachytherapy was used in 15, and external alone in 45. Two patients with Stage
      IVA received brachytherapy alone, 10 received a combination of external and
      brachytherapy, and 6 received external irradiation alone. Total doses ranged from
      10 to 154 Gy (mean 74.7 Gy, median 70.0 Gy), but only 18 (6%) received less than
      55 Gy. At a median follow-up of 13 years, the 5-, 10-, 15-, 20-, and 25-year
      survival rates were 60%, 49%, 38%, 29%, and 23%, respectively. Beyond 5 years the
      survival rates relative to those for age-matched females in the general
      population were between 50 and 65%. Actuarial local recurrence rates were 23%,
      26%, and 26% at 5, 10, and 15 years. Actuarial pelvic relapse rates were 26%,
      30%, and 31% at 5, 10, and 15 years, and metastatic rates at those times were
      15%, 18%, and 18%. Adenocarcinoma (nonclear cell) was a significantly worse
      disease than squamous cell carcinoma. The major determinants of local control for
      squamous carcinoma were tumor bulk (specified by size in centimeters, or by FIGO
      stage), tumor site (upper lesions faring better than others), and tumor
      circumferential location (lesions involving the posterior wall faring worse).
      Tumor bulk was an important determinant of metastatic relapse, but failure to
      achieve local control was also an independently significant determinant of
      metastases. Salvage after first relapse was uncommon and the survival rate at 5
      years after relapse was only 12%. Serious complications occurred in 39 patients
      with an actuarial incidence of 19% at 20 years. CONCLUSION: Vaginal carcinoma
      poses a formidable therapeutic challenge. The disease is heterogeneous with
      respect to its prognostic factors. Nonclear cell adenocarcinoma has an extremely
      poor prognosis and should be distinguished from squamous carcinoma. Both external
      beam and brachytherapy play crucial roles in management and most patients with
      disease beyond in situ should receive a significant component of external
      irradiation prior to brachytherapy.

PMID- 8751396
TI  - Potency following conformal neutron/photon irradiation for localized prostate
      cancer.
AB  - PURPOSE: To assess the effect of conformal neutron/photon irradiation with or
      without neoadjuvant hormonal therapy on posttreatment potency. MATERIALS AND
      METHODS: Seventy-six patients with localized adenocarcinoma of the prostate,
      State T1 or T2 N0 M0, Gleason score < or = 7, were enrolled on a prospective
      Phase II study. Each patient received 9-10 Neutron + 38 Photon Gy. Twenty-eight
      patients received neoadjuvant hormonal therapy in conjunction with radiation
      therapy. Potency was assessed prior to starting treatment and was assessed at
      each subsequent follow-up visit. RESULTS: Fifty-two of patients (70%) were potent
      at the start of therapy. Thirty-eight of 52 (73%) had functional erections and 14
      of 52 (27%) had erections termed nonfunctional, which were of insufficient
      strength for intercourse. After treatment, 35 of 52 (67%) retained potency.
      Twenty-nine of 38 (76%) with functional erections pretreatment maintained this
      ability. Only 6 of 14 patients (43%) with nonfunctional erection pretreatment
      maintained their level of potency. Neoadjuvant hormonal therapy did not impact on
      the ability to maintain erections. Sixty-five percent of those patients receiving
      hormones retained erectile function, while 69% of those who did not receive
      hormones maintained erectile function. Age was not a significant factor in
      posttreatment potency, although a trend towards potency in younger patients was
      observed. (p = 0.74). CONCLUSION: The majority (67%) of patients maintained their
      level of erectile function following conformal sequential neutron photon
      irradiation. This is comparable to that achieved with photon irradiation alone.
      No significant change in potency was seen with neoadjuvant hormonal therapy or
      with increasing patient age.

PMID- 8751399
TI  - Fractionation in medium dose rate brachytherapy of cancer of the cervix.
AB  - PURPOSE: To establish an optimum fractionation for medium dose rate (MDR)
      brachytherapy from retrospective data of patients treated with different MDR
      schedules in comparison with a low dose rate (LDR) schedule. METHODS AND
      MATERIALS: The study population consists of consecutive Stage IB-IIA-IIB patients
      who received radiotherapy alone with full dose brachytherapy plus external beam
      pelvic and parametrial irradiation from 1986-1993. Patients also receiving
      surgery or chemotherapy were excluded. The LDR group (n = 102, median follow-up:
      80 months) received a median dose to Point A of two 32.5 Gy fractions at 0.44
      Gy/h plus 18 Gy of external whole pelvic irradiation. The MDR1 group (n = 30,
      median follow-up: 45 months) received a mean dose of two 32 Gy fractions at 1.68
      Gy/h. An individual dose reduction of 12.5% was planned for this group according
      to the Manchester experience, but only a 4.8% dose reduction was achieved. The
      MDR2 group (n = 10, median follow-up: 36 months) received a dose of two 24 Gy
      fractions at 1.65 Gy/h. The MDR3 group (n = 10, median follow-up 33 months)
      received a mean dose of three 15.3 Gy fractions at 1.64 Gy/h. And finally, the
      MDR4 group (n = 38, median follow-up: 24 months) received six 7.7 Gy fractions
      from two pulses 6 h apart in each of three insertions at 1.61 Gy/h. The median
      external pelvic dose to MDR schedules was between 12 and 20 Gy. The linear
      quadratic (LQ) formula was used to calculate the biologically effective dose
      (BED) to tumor (Gy10) and rectum (Gy3), assuming T1/2 for repair = 1.5 h.
      RESULTS: The crude central recurrence rate was 6% for LDR (mean BED = 95.4 Gy10)
      and 10% for MDR4 (mean BED = 77.0 Gy10) (p = NS). The remaining MDR groups had no
      recurrences. Grade 2 and 3 rectal or bladder complications were 0% for LDR
      (rectal BED = 109 Gy3) 83% for MDR1 (BED = 206 Gy3), and 30% for MDR3 (BED = 127
      Gy3). The MDR2 and MDR4 groups presented no complications (BED, 123 Gy3, and 105
      Gy3, respectively). The LQ formula appears to correlate with late complications
      of the different MDR regimens. A BED above 125 Gy3 was associated with Grade 2 +
      3 rectal complications. Adequate central tumor control may be compromised with a
      tumor BED below 90-95 Gy10. CONCLUSIONS: Medium dose rate brachytherapy at 1.6
      Gy/h to Point A has a marked dose rate effect. Increased fractionation is the
      cost of overcoming the less favorable therapeutic ratio for MDR than for LDR. A
      larger (25%) reduction of brachytherapy dose than previously reported is also
      necessary. Our most recently developed schedule for Stage I-II patients is three
      insertions on three treatment days with six 8.0 Gy brachytherapy fractionations,
      two on each treatment day, following or preceding an external whole pelvis dose
      of 18 Gy, and followed by additional external parametrial dose.

PMID- 8751401
TI  - Improved outcome in patients treated with postoperative radiation therapy for
      pathologic stage I/II endometrial cancer.
AB  - PURPOSE: To evaluate prognostic factors and treatment outcome for high risk
      pathological Stage I and II endometrial cancer patients treated with consistent
      postoperative radiation therapy (RT) in a single institution and to compare these
      results to series where RT was variably applied. METHODS AND MATERIAL: Between
      1986 and 1993, 98 pathologic Stage I and II endometrial cancer patients received
      postoperative RT at the Fox Chase Cancer Center. Papillary serous and clear cell
      histologies were excluded. Fifty-five patients underwent lymph node evaluation.
      In 17 patients, RT consisted of intracavitary brachytherapy alone to a median
      dose of 21 Gy, and in 81 patients, RT consisted of external beam RT to a median
      dose of 45 Gy followed by intracavitary brachytherapy to a median dose of 12 Gy.
      Intracavitary brachytherapy generally consisted of three high dose rate implants
      with the dose prescribed to a depth of 0.5 cm. Median follow up was 47 months.
      RESULTS: The 5-year overall survival (OS), disease free survival (DFS), and
      freedom from pelvic recurrence (FPR) rates were 83, 85, and 89%, respectively.
      Pelvic recurrence either as the sole pattern of failure or combined with distant
      metastases was seen in 2 and 7% of patients, respectively. Distant metastases
      alone occurred in 4% of the patients. Univariate analysis of prognostic factors
      including age, grade, capillary lymphatic space invasion, depth of myometrial
      invasion, type of lymph node evaluation, pathologic stage, the use of
      brachytherapy and the number of risk factors was performed for OS, DFS, FPR, and
      FDM. Capillary lymphatic space invasion was the only statistically significant
      predictor for reduced DFS. Absence of lymph node dissection as well as a higher
      number of risk factors showed a trend toward poorer DFS (p = 0.06 for both).
      Multivariate analysis revealed older age to be the only factor significant for
      reduced DFS, with the presence of capillary lymphatic space invasion and the
      absence of a lymph node dissection showing a trend toward poorer outcome (p =
      0.07). CONCLUSIONS: The results of this study suggest a continued role for the
      use of postoperative RT in the treatment of patients with high risk endometrial
      cancer and will be compared to other series with similar high-risk factors.

PMID- 8751400
TI  - Usefulness of tumor volumetry by magnetic resonance imaging in assessing response
      to radiation therapy in carcinoma of the uterine cervix.
AB  - PURPOSE: Clinical evaluation of tumor size in cervical cancer is often difficult,
      and clinical signs of radiation therapy failure may not be present until well
      after completion of treatment. The purpose of this study is to investigate early
      indicators of treatment response using magnetic resonance (MR) imaging for
      quantitative assessment of tumor volume and tumor regression rate before, during,
      and after radiation therapy. METHODS AND MATERIALS: Thirty-four patients with
      cervical cancer Stages IB [5], IIB [8], IIIA [1], IIIB [14], IVA [3], IVB [1],
      and recurrent [2] were studied prospectively with four serial MR examinations
      obtained at the start of radiation therapy, at 2-2.5 weeks (20-24 Gy), at 4-5
      weeks (40-50 Gy), and 1-2 months after treatment completion. Tumor volume was
      assessed by three-dimensional volumetric measurements using T2-weighted images of
      each MR examination. The volume regression rate was generated based on the four
      sequential MR studies. These findings were correlated with local control,
      metastasis rate, and disease-free survival. Median follow-up was 18 months
      (range: 9-43 months). RESULTS: The tumor regression rate after a dose of 40-50 Gy
      correlated significantly with treatment outcome. The actuarial 2-year disease
      free survival was 88.4% in patients with tumors regressing to < 20% of the
      initial volume compared with 45.4% in those with > or = 20% residual (p = 0.007).
      The incidence of local recurrence was 9.5% (2 out of 21) and 76.9% (10 out of
      13), respectively (p < 0.001). Analysis by initial tumor volume showed that this
      observation was valid in patients with initial volumes between 40 and 100 cm3.
      Analysis by FIGO stage confirmed this observation in all patients except those
      with Stage IB. CONCLUSION: Sequential tumor volumetry using MR imaging appears to
      be a sensitive measure of the responsiveness of cervical cancer to irradiation.
      Treatment response can be assessed as early as during the course of radiation
      therapy by measurement of initial tumor volume and regression rate at 40-50 Gy.
      In patients with large (> 40 cm3) and advanced (Stage > or = IIIA) tumors, this
      technique may be helpful in supplementing the clinical examination for response
      assessment. The identification of patients at high risk for treatment failure may
      ultimately lead to improved clinical outcome.

PMID- 8751402
TI  - Prognostic characteristics of surgical stage I endometrial adenocarcinoma.
AB  - PURPOSE: To evaluate and correlate the expression of pathologic characteristics,
      flow cytometric DNA content analysis, and estrogen and progesterone receptor
      levels with survival in patients with surgical Stage I endometrial carcinoma.
      METHODS AND MATERIALS: Hospital tumor registry records were surveyed, and this
      identified 232 patients diagnosed with endometrial adenocarcinoma between July 1,
      1989, and December 30, 1993. DNA content analysis was performed on either
      paraffin-embedded or fresh tissue samples. Survival was calculated from the date
      of diagnosis by the Kaplan-Meier method. Postoperative irradiation (whole pelvis
      external beam therapy and low dose rate vaginal cuff brachytherapy) was delivered
      to patients felt to be at high risk for failure. RESULTS: One hundred seventy-one
      patients had Stage I tumors and were available for analysis. Patients with Stage
      1C tumors had a statistically significant lower survival rate compared to
      patients with Stages IA or IB (p = 0.03 and p < 0.01, respectively). Patients
      with DNA content diploid tumors had a slightly increased (but nonsignificantly
      so) survival compared to patients with non-DNA content diploid tumors (p = 0.12).
      Logistic regression analysis failed to identify an independent prognostic factor
      that could predict for disease specific survival in patients with Stage I
      cancers. CONCLUSION: Logistic regression analysis did not identify a single
      independent prognostic factor in patients with Stage I tumors. Pathologic
      characteristics reported to predict survival advantage correlated with pathologic
      stage. Additional translational research is needed to identify molecular
      characteristics of tumors that may indicate more aggressive treatment for
      patients at high risk for recurrence.

PMID- 8751403
TI  - Radiation survival of two human cervical carcinoma cell lines after multifraction
      irradiation.
AB  - PURPOSE: Multifraction irradiation may contribute to radiation therapy treatment
      failure if selection of radiation resistant subpopulations occurs. We sought to
      determine whether surviving cells following daily fraction irradiation of two
      human cervical squamous cell carcinoma lines would express different radiation
      survival characteristics compared to the unirradiated parent. METHODS AND
      MATERIALS: A late-passage line (HTB35) and an early-passage line (RECA) received
      daily 2 Gy x-irradiation. Two new stable HTB35 cell lines were established after
      40 and 60 Gy (HTB35-40 and HTB35-60). A single line was established from RECA
      after 30 Gy (RECA-30). High dose rate (74 cGy/min) acute radiation survival
      curves were prepared from the three new lines and the unirradiated parents.
      Potentially lethal damage repair (PLDR) and sublethal damage repair (SLDR)
      responses were detailed for HTB35, HTB35-40 and HTB35-60. Low dose rate (1.27
      cGy/min) survival was measured for HTB35 and HTB35-60. Clones were derived from
      HTB35 and from HTB35-60 and the surviving fraction at 2 Gy (SF2) values were
      determined. RESULTS: The two parent lines (HTB35 and RECA) differed in acute
      radiation survival. The surviving lines following multifraction irradiation
      (HTB35-40, HTB35-60, and RECA-30) showed no change in acute radiation response
      compared to the appropriate parent. HTB35-40 and HTB35-60 were repair proficient,
      demonstrating similar PLDR and SLDR recovery ratios as the parent. Likewise,
      acute, low dose rate survival of HTB35 and HTB35-60 was similar. Nine clones
      derived from HTB35 lacked a consistent difference in SF2 compared to the original
      culture. A single clone of seven derived from HTB35-60 was consistently radiation
      resistant (SF2 = 0.81 +/- 0.06) compared to the original culture (SF2 = 0.50 +/-
      0.09). CONCLUSION: No evidence was obtained that cell lines generated following
      multiple daily fractions of x-irradiation in vitro possessed acute radiation
      survival or repair characteristics that were different from the unirradiated
      parent.

PMID- 8751404
TI  - Accelerated repopulation during fractionated irradiation of a murine ovarian
      carcinoma: downregulation of apoptosis as a possible mechanism.
AB  - PURPOSE: To test whether accelerated tumor clonogen repopulation occurs during
      continuous fractionated radiotherapy of a slow-growing mouse ovarian tumor, and
      if so whether the accelerated rate of repopulation is predicted by the
      pretreatment potential doubling time, and whether changes in apoptotic response
      are a possible mechanism for this change. METHODS AND MATERIALS: The rate of
      clonogen production during fractionated radiotherapy was followed using the tumor
      control assay, with an independent determination of the sensitivity to repeated
      dose fractions in vivo in the absence of repopulation. The pretreatment potential
      doubling time was measured by bromodeoxyuridine (BrdUrd) labeling and
      fluorescence measurements. The apoptotic and mitotic indices at various times
      during treatment were scored histologically. RESULTS: The slow-growing
      (pretreatment volume doubling time 6 days) ovarian tumor OCA responds to daily
      irradiation with 6 Gy under hypoxia by negligible tumor clonogen production in
      the first few days, followed by a change at about 9 days to accelerated
      repopulation, after which the effective clonogen doubling time Tclon was about 2
      days, near the pretreatment Tpot of 1.7 days. Alternative interpretations of the
      data, such as a change in radiosensitivity vs. a change in the repopulation rate
      or acceleration at 3 days as opposed to 9 days, were shown to be unlikely. This
      change was accompanied by a reduced apoptotic response (measured
      morphometrically). CONCLUSIONS: When sensitivity to fractionated doses has been
      corrected for in vivo, this slow-growing mouse tumor exhibits a change to
      accelerated clonogen production during a continuous radiotherapy regimen that is
      accompanied or preceded by a reduced histologic apoptotic response. Tclon during
      accelerated repopulation was slightly longer than the pretreatment Tpot.

PMID- 8751405
TI  - DNA supercoiling changes and nuclear matrix-associated proteins: possible role in
      oncogene-mediated radioresistance.
AB  - PURPOSE: Transfection with either H-ras or H-ras and c-myc has been shown to
      confer radioresistance in rat embryonal cells (REC). REC primary, transfected
      with either c-myc, H-ras or cotransfected with c-myc and H-ras (in ascending
      order of radioresistance and tumorigenicity), were used as an in vitro model
      system to determine if nuclear matrix-mediated higher order DNA organization
      contributes to oncogene-mediated radioresistance. METHODS AND MATERIALS: DNA
      damage induction and repair were measured by the alkaline and neutral filter
      elution assays. Analysis of the ability of DNA loop domains to undergo
      supercoiling changes in the presence of radiation-induced damage was determined
      by the fluorescent halo assay (FHA). Because DNA loops are organized by the
      nuclear matrix (NM), a study of NM-associated proteins by high resolution two
      dimensional gel electrophoresis was performed. RESULTS: Induction and repair
      rates of DNA single- and double-strand breaks were similar for the relatively
      radiosensitive c-myc transfected and the radioresistant c-myc + H-ras transfected
      cells. However, the degree of inhibition of DNA supercoil rewinding in the
      presence of radiation-induced damage was less in the radioresistant cells and was
      inversely correlated with survival. A progressive loss of NM-associated proteins
      was observed, which correlated with increasing radioresistance and tumorigenicity
      in these cell lines. In addition, some protein changes were consistent with the
      possibility that these changes could be involved in DNA anchoring. CONCLUSIONS:
      Increased radioresistance associated with increasing tumorigencity in these
      oncogene-transfected cell lines could be due to changes in NM-mediated DNA
      organization, possibly via differences in NM protein composition that occur
      following oncogenic transfection.

PMID- 8751406
TI  - Ultrasound image fusion for external beam radiotherapy for prostate cancer.
AB  - PURPOSE: To determine whether real-time ultrasound imaging and targeting system
      for the treatment of prostate cancer was feasible. The initial phase of this
      project included a study to develop and determine (a) software for the fusion of
      ultrasound images to standard x-rays obtained during simulation, and (b) the
      potential reduction in field size with real-time imaging. METHODS AND MATERIALS:
      During 13 patient simulations a transrectal ultrasound image was obtained.
      Orthogonal x-ray films were acquired with the rectal probe in place. Both the x
      ray and ultrasound images were digitized and a fusion image was created of the
      prostate position in relation to the probe, bladder, and rectum. The two
      dimensional area of the rectum, bladder, and prostate was determined in the
      lateral projection. Potential conformal blocks were designed for the lateral
      portals in a four-field treatment technique. RESULTS: The transrectal ultrasound
      probe enabled real-time prostate imaging. The lateral field size can be reduced
      to 6.08 x 5.68 cm2 +/- 0.62 x 0.48 cm2 from the standard 8 x 8 cm2 field. The
      posterior rectal wall was physically displaced out of the lateral field. The area
      of the rectum included in the lateral field is 1.75 cm2 +/- 0.85 cm2. CONCLUSION:
      The prostate position can be determined with certainty on a regular basis with
      transrectal ultrasonography. The amount of normal tissue in the high dose volume
      can be reduced. This approach may reduce acute and chronic morbidity and allow
      further dose escalation.

PMID- 8751407
TI  - An observer study for direct comparison of clinical efficacy of electronic to
      film portal images.
AB  - PURPOSE: To directly compare clinical efficacy of electronic to film portal
      images. METHODS AND MATERIALS: An observer study was designed to compare clinical
      efficacy of electronic to film portal images acquired using a liquid matrix ion
      chamber electronic portal imaging device and a conventional metal screen/film
      system. Both images were acquired simultaneously for each treatment port and the
      electronic portal images were printed on gray-level thermal paper. Four radiation
      oncologists served as observers and evaluated a total of 44 sets of images for
      four different treatment sites: lung, pelvis, brain, and head/neck. Each set of
      images included a simulation image, a double-exposure portal film, and video
      paper prints of electronic portal images. Eight to nine anatomical landmarks were
      selected from each treatment site. Each observer was asked to rate each landmark
      in terms of its clinical visibility and to rate the ease of making the pertinent
      verification decision in the corresponding electronic and film portal images with
      the aid of the simulation image. RESULTS: Ratings for the visibility of landmarks
      and for the verification decision of treatment ports were similar for electronic
      and film images for most landmarks. However, vertebral bodies and several
      landmarks in the pelvis such as the acetabulum and public symphysis were more
      visible in the portal film images than in the electronic portal images.
      CONCLUSION: The visibility of landmarks in electronic portal images is comparable
      to that in film portal images. Verification of treatment ports based only on
      electronic portal images acquired using an electronic portal imaging device is
      generally achievable.

PMID- 8751408
TI  - Abdomino-pelvic hyperthermia and intraperitoneal carboplatin in epithelial
      ovarian cancer: feasibility, tolerance and pharmacology.
AB  - PURPOSE: To investigate the feasibility, toxicity, and pharmacokinetics of
      intraperitoneal (i.p.) carboplatin (CB) with concomitant abdomino-pelvic
      hyperthermia (HT) in advanced ovarian cancer patients. METHODS AND MATERIALS:
      Patients with residual disease mainly confined to the peritoneal cavity after
      platinum based chemotherapy received an initial course of i.p. CB for baseline
      pharmacokinetics followed by three cycles of i.p. CB with concomitant regional
      hyperthermia. The goal of HT was to achieve at least 45 min of intraperitoneal
      temperature > 42 degrees but < 50 degrees C while maintaining normal tissue
      temperatures < 43 degrees C and systemic body temperatures < 38 degrees C. No
      analgesic premedication was used. Thermometry was recorded by multisensor
      fiberoptic probes placed within the peritoneal cavity, bladder, vagina, and oral
      cavity. RESULTS: Thirteen patients received a total of 31 sessions. Our
      intraperitoneal temperature goal could not be achieved because of patient
      intolerance. At best, we could maintain intraperitoneal temperatures > 40 degrees
      C, for more than 40 min in 7 of 31 sessions. The average values of thermal
      variables were T90 = 40 degrees C, TAVE = 41 degrees C, TMIN = 38.2 degrees C,
      and TMAX = 42.9 degrees C. The mean maximum systemic temperature was 38 degrees
      C. Acute thermal toxicities requiring early interruption of hyperthermia were
      systemic temperature exceeding 38 degrees C (11 of 31), abdominal pain or
      generalized distress (20 of 31), and vomiting (2 of 31). Hematological toxicities
      were not increased by hyperthermia. Pharmacokinetics were consistent with
      enhanced clearance of CB by HT. Lower radio frequencies (< 75 MHz) achieved
      better heat deposition in the peritoneal cavity than higher frequencies (> 75
      MHz). Two of the 13 patients (a Stage III and a Stage IV patient) are alive with
      no evidence of disease at 40 and 43 months from treatment. CONCLUSIONS:
      Intraperitoneal temperatures in the range of 40 degrees C maintained for
      approximately 40 min can be achieved within the described setting. The
      probability of successful induction of therapeutic intraperitoneal temperatures
      appears to be higher when frequencies below 75 MHz are used. Patients who are
      potentially platinum sensitive and have minimal residual disease could
      potentially benefit from the combined treatment under the conditions studied.
      However, this temperature-time range appears inadequate against platinum
      resistant disease, and/or bulky residual pelvic disease. Alternative approaches
      such as whole body hyperthermia and carboplatin are warranted to overcome some of
      the obstacles observed.

PMID- 8751409
TI  - A retrospective study of the effects of pelvic irradiation for gynecological
      cancer on anorectal function.
AB  - PURPOSE: To evaluate the prevalence of anorectal dysfunction following
      therapeutic pelvic irradiation. METHODS AND MATERIALS: Anorectal function was
      evaluated in 15 randomly selected patients (aged 47-84 years) who had received
      pelvic irradiation for treatment of carcinoma of the uterine body and cervix 5
      and 10 years earlier. The following parameters were assessed in each patient: (a)
      anorectal symptoms (questionnaire), (b) anorectal pressures at rest and in
      response to rectal distension, voluntary squeeze, and increases in intraabdominal
      pressure (multiport anorectal manometry with concurrent electromyography of the
      anal sphincters), (c) rectal sensation (rectal balloon distension) and, (d) anal
      sphincteric morphology (ultrasound). Results were compared with those obtained in
      nine female control subjects. RESULTS: Ten of the 15 patients had urgency of
      defecation and 4 also suffered fecal incontinence. Basal anorectal pressures
      measured just proximal to the anal canal (p = 0.05) and anorectal pressures
      generated in response to voluntary squeeze measured at the anal canal were less
      (p < 0.01) in the patients. The fall in anal pressures in response to rectal
      distension was greater in the patients (p < 0.05) and the desire to defecate
      occurred at lower rectal volumes (p < 0.05). The slope of the pressure/volume
      relationship in response to rectal distension was greater (p < 0.05) in the
      patients, suggestive of a reduction in rectal compliance. In 14 of the 15
      patients at least one parameter of anorectal motor function was outside the
      control range. There was no difference in the thickness of the anal sphincters
      between the two groups. CONCLUSION: Abnormal anorectal function occurs frequently
      following pelvic irradiation for gynecological malignant diseases and is
      characterized by multiple dysfunctions including weakness of the external anal
      sphincter, stiffness of the rectal wall, and a consequent increase in rectal
      sensitivity.

PMID- 8751410
TI  - Prostate volumes defined by magnetic resonance imaging and computerized
      tomographic scans for three-dimensional conformal radiotherapy.
AB  - PURPOSE: To compare the prostate volumes defined on magnetic resonance imaging
      (MRI), and noncontrast computerized tomographic (CT) scans used for three
      dimensional (3D) treatment planning. METHODS AND MATERIALS: Ten patients were
      simulated for treatment using immobilization and a retrograde urethrogram. 3D
      images were used to compare prostate volumes defined by MRI (4-6 mm thick slices)
      and CT images (5 mm thick slices). Prostate volumes were calculated in cm(3)
      using the Scanditronix 3D planning system. MRI/CT images were merged using bony
      anatomy to define the regions of discrepancy in prostate volumes. RESULTS: The
      mean prostate volume was 32% larger (range-5-63%) when defined by noncontrast CT
      compared to MRI. The areas of nonagreement tended to occur in four distinct
      regions of discrepancy: (a) the posterior portion of the prostate, (b) the
      posterior-inferior-apical portion of the prostate, (c) the apex due to
      disagreement between a urethrogram based definition and the location defined by
      MRI, (d) regions corresponding to the neurovascular bundle. CONCLUSION: There is
      a tendency to overestimate the prostate volume by noncontrast CT compared to MRI.
      Awareness of this tendency should allow us to be to more accurately define the
      prostate during 3-D treatment planning.

PMID- 8751411
TI  - The "critical volume tolerance method" for estimating the limits of dose
      escalation during three-dimensional conformal radiotherapy for prostate cancer.
AB  - PURPOSE: To describe the "Critical Volume Tolerance" (CVT) method for defining
      normal tissue tolerance during 3D-based dose escalation studies for prostate
      cancer. METHODS AND MATERIALS: The CVT method predicts the tolerance to radiation
      for "in series"-type functional units based on the assumption that tolerance
      depends on a critical threshold "low-volume high-dose region." The data used for
      describing this model were generated from 3D analysis of randomly selected
      patients with prostate cancer. Commonly used coplanar four-and six-field
      conformal (SFC) techniques were chosen as the comparison techniques. For purposes
      of comparison, rectal tolerance was assumed to be reached following whole pelvic
      irradiation using a four-field box technique to 50 Gy, followed by a conedown
      boost to 70 Gy using bilateral 9 x 9 cm 120 degree arcs as popularized by
      investigators from Stanford University (SUH). RESULTS: Based on the average dose
      volume histograms for the patients studied, the maximum safe increase in dose for
      the SFC technique compared to the SUH technique, would be 10% if 30% of the
      rectal volume was the critical dose limiting volume (CVT = 30%), 5% if the CVT =
      10%, or greater than 20% if the CVT = 40%. Commonly used four-field conformal
      techniques would not be expected to allow significant escalation of the dose
      without increasing the risk of complications. CONCLUSIONS: The CVT method is
      relatively simple, and data generated based on it can be used to support normal
      tissue complication probability equations. The CVT method can be verified or
      modified as partial tolerance data become available. Based on the CVT model,
      sophisticated treatment techniques should allow a modest increase in the total
      dose of radiation delivered to the prostate without an increase in late
      complications.

PMID- 8751412
TI  - Combined error of patient positioning variability and prostate motion uncertainty
      in 3D conformal radiotherapy of localized prostate cancer.
AB  - PURPOSE: To measure the patient positioning and prostate motion variability and
      to estimate its influence on the calculated 3D dose distribution in 3D conformal
      radiotherapy of patients with localized prostate carcinoma. METHODS AND
      MATERIALS: Patient positioning variability was determined retrospectively by
      comparing 54 orthogonal simulator films with 125 corresponding portal films from
      27 patients. Prostate motion variability was determined by 107 computed
      tomography (CT) examinations with a CT simulator in 28 patients during
      radiotherapy. RESULTS: In each observed direction, the patient positioning
      variability and prostate motion showed a normal distribution. This observation
      enabled the calculation of a combined error of both components. The standard
      deviation (1 SD) of the patient positioning error in three directions ranged from
      3.1 to 5.4 mm; the prostate motion variability was significantly greater in the
      anterior-posterior direction (1 SD = 2.8 mm) than in the mediolateral direction
      (1 SD = 1.4 mm). The 1 SD of the estimated combined error was in the anterior
      posterior direction 6.1 mm and in mediolateral direction 3.6 mm. CONCLUSION: The
      range of patient positioning variability and prostate motion were statistically
      predictable under the patient setup conditions used. Dose-volume histograms
      demonstrating the influence of the combined error of both components on the
      calculated dose distribution are presented.

PMID- 8751413
TI  - Major geometric variations between intracavitary applications in carcinoma of the
      cervix: high dose rate vs. low dose rate.

PMID- 8751414
TI  - Preoperative radiotherapy in rectal carcinoma--aspects of acute adverse effects
      and radiation technique.
AB  - PURPOSE: To explain a possible association between treatment technique and
      postoperative mortality after preoperative radiotherapy of rectal carcinoma, the
      dose distributions were compared in model experiments. METHODS AND MATERIALS:
      Preoperative radiotherapy with a three-beam technique delivered in five fractions
      to 25 Gy (5 Gy/daily for 5 or 7 days) was given to patients with primary
      resectable rectal carcinoma. The adverse effects of this treatment, both acute
      and late, have been low. In a parallel trial using an identical fractionation
      schedule and total dose but with a two-beam technique, the postoperative
      mortality was higher. Two-, three-, and four-beam techniques were analyzed in 20
      patients with computed tomography based, three-dimensional dose planning. Dose
      distributions and dose-volume histograms in the planning target volume (PTV) and
      in the organs at risk were considered. A numerical "biological" model was used to
      compare the techniques. RESULTS: The two-beam and the four-beam box techniques
      give the most homogeneous dose distributions in the PTV, although all techniques
      result in dose distributions that would be considered adequate, provided 16 MV or
      higher photon energies are used. Three- and four-beam techniques show advantages
      over the two-beam technique with respect to organs at risk, particularly the
      small bowel. With the two-beam technique and the upper beam limit at mid-L4, the
      volume of the bowel that receives > 95% of the prescribed dose, and hence, is
      included in the treated volume (TV), is more than twice as large as that with
      three- and four-beam techniques, and that of the total body between 1.5 and 2
      times as large. The results of the analyses using the biological model indicate
      that the three- and four-beam techniques result in less small bowel complication
      rates than the two-beam technique. The integral energy to the total body is
      similar for all treatment modalities compared. CONCLUSIONS: The volume of bowel
      included in the TV, rather than the energy imparted to the body, influences
      postoperative mortality, and emphasizes the importance of precise radiotherapy
      planning to minimize normal tissue toxicity.

PMID- 8751415
TI  - Evaluation of a pencil-beam dose calculation technique for charged particle
      radiotherapy.
AB  - PURPOSE: The purpose of this article is to evaluate a pencil-beam dose
      calculation algorithm for protons and heavier charged particles in complex
      patient geometries defined by computed tomography (CT) data and to compare
      isodose distributions calculated with the new technique to those calculated with
      conventional algorithms in selected patients with skull-base tumors. METHODS AND
      MATERIALS: Monte Carlo calculations were performed to evaluate the pencil-beam
      algorithm in patient geometries for a modulated 150-MeV proton beam. A modified
      version of a Monte Carlo code described in a previous publication (18) was used
      for these comparisons. Tissue densities were inferred from patient CT data on a
      voxel-by-voxel basis, and calculations were performed with and without tissue
      compensators. A dose calculation module using the new algorithm was written, and
      treatment plans using the new algorithm were compared to plans using standard ray
      tracing techniques for 10 patients with clival chordoma and three patients with
      nasopharyngeal carcinoma who were treated with helium lons at Lawrence Berkeley
      National Laboratory (LBL). RESULTS: Pencil beam calculations agreed well with
      Monte Carlo calculations in the patient geometries. The pencil-beam algorithm
      predicted several multiple-scattering effects that are not modeled by
      conventional ray-tracing calculations. These include (a) the widening of the
      penumbra as a function of beam penetration, (b) the degradation in the sharpness
      of the dose gradient at the end of the particle range in highly heterogeneous
      regions, and (c) the appearance of hot and cold dose regions in the shadow of
      complex heterogeneities. In particular, pencil-beam calculations indicated that
      the dose distribution within the target was not as homogeneous as expected on the
      basis of ray-tracing calculations. On average, for the 13 patients considered,
      only about 72% of the conedown target volume received at least 99% of the
      prescribed dose, whereas, 93% of the conedown volume was contained within the 95%
      isodose surface. This may be significant because in standard charged particle
      dose calculations, the dose across the spread-Bragg peak is assumed to be uniform
      and equal to the maximum or prescribed dose. CONCLUSIONS: Dose distributions
      computed with the pencil-beam model are more accurate than ray-tracing
      calculations, providing additional information to clinicians, which may influence
      the doses they prescribe. In particular, these calculations indicate that for
      some patients with skull-base tumors, it may be advantageous to prescribe proton
      doses to a lower isodose level than is commonly done.

PMID- 8751416
TI  - A simple and generally applicable method to estimate the peripheral dose in
      radiation teletherapy with high energy x-rays or gamma radiation.
AB  - PURPOSE: Many articles have been published on the measurement of the dose to
      points outside the primary beam, often called the peripheral dose (PD), for
      instance, to the gonads, for specific treatment machines and/or techniques. We
      investigated the possibilities for developing a generalized method based on the
      data from several publications. METHODS AND MATERIALS: The data from several
      publications were recalculated for a reference situation, then averaged, and the
      frequency distributions around the mean were determined. Published data were
      available for 60Co, 4, 6, 8, and 10 MV, and 18 to 25 MV for a large variety of
      treatment machines. Furthermore, an analysis of possible corrections for depth
      dependence, field elongation, irregularly shaped fields, wedges, and shielding
      blocks was carried out. RESULTS: The frequency distributions of all published PD
      values for square fields for photon energies of 4 MV to 25 MV showed a standard
      deviation of 33%. The PD values of 60Co are significantly different with a
      standard deviation of 25%. A difference in the leakage radiation between cobalt
      machines and linear accelerators can possibly explain this difference, especially
      for large distances, where leakage radiation predominates. Taking the uncertainty
      of the risk factors into consideration, we conclude that the use of average
      values is justified. Although statistically not significant, the peripheral dose
      appears to be dependent on photon energy with a minimum around 6 MV. CONCLUSIONS:
      It is possible to estimate the peripheral dose for photon energies of 4 MV to 25
      MV with an accuracy of +/- 33%; for 60Co, the accuracy is even better. The
      variation of the PD between different treatment machines is so small that it is
      justified to use average PD values, irrespective of the treatment machine.

PMID- 8751417
TI  - History of radiotherapy in Turkey.

PMID- 8751418
TI  - Radiotherapy in Macedonia.

PMID- 8751419
TI  - Radiation oncology in Spain: historical notes for the radiology centennial.

PMID- 8751420
TI  - The clinical significance of ratios of radiobiological parameters.
AB  - PURPOSE: Interindividual heterogeneity of the radiobiological characteristics of
      malignant and normal tissues hampers the derivation of radiobiological parameters
      from clinical data. Focusing on the ratio Dprolif, i.e., the dose to compensate 1
      day of treatment interruption, this article investigates the hypothesis that
      ratios of parameters might be less sensitive to interpatient heterogeneity and
      may constitute a more reliable description of the radiobiological properties of
      tissues than the parameters themselves. METHODS AND MATERIALS: Analytic
      calculations were performed in an idealized example in which the only source of
      heterogeneity was the number of clonogenic cells. Computer simulations were used
      to assess the effects of heterogeneity in radiosensitivity and in proliferative
      capacity. Treatment outcome was simulated in pseudopatients with increasing dose
      time correlation. RESULTS: Interindividual heterogeneity in clonogenic cell
      number, radiosensitivity, or proliferative ability results in a marked
      underestimation of the response parameters describing these processes. In
      contrast, the estimates of the ratio Dprolif were more stable. The coefficients
      of variation increased with increasing heterogeneity. However, this only became
      unacceptable when heterogeneity in radiosensitivity was marked, or when total
      dose and treatment time were closely correlated. CONCLUSION: Parameter ratios may
      provide more robust radiobiological information than single parameters estimated
      from clinical data except when interindividual heterogeneity is very large or
      when the treatment modalities are too highly correlated. As usual, caution is
      advised in the presence of patient selection, a correlation between treatment
      prescription and expected outcome, or limited ranges of dose-time treatment
      patterns.

PMID- 8751421
TI  - Magnetic resonance tumor volumetry in cervical cancer.

PMID- 8751422
TI  - PSA following irradiation for prostate cancer: the upcoming ASTRO symposium.

PMID- 8751423
TI  - Efficacy of adjuvant hyperthermia in the treatment of superficial recurrent
      breast cancer: confirmation and future directions.

PMID- 8751424
TI  - p53 protein expression or protein function?

PMID- 8751425
TI  - In vitro and in vivo radiation sensitivity of glioblastoma multiforme:
      correction.

PMID- 8751426
TI  - Ethics worries over execution twist to Internet's 'visible man'.

PMID- 8751428
TI  - Hushed tones of the whistleblower.

PMID- 8751427
TI  - Roche faces charges over Taq patent claim.

PMID- 8751429
TI  - Significance of birth-dates.

PMID- 8751430
TI  - Universal spelling.

PMID- 8751431
TI  - Natural resistance to HIV?

PMID- 8751432
TI  - A triumph for common scents.

PMID- 8751433
TI  - Breast cancer. What's mice got to do with it?

PMID- 8751434
TI  - Alzheimer's disease. Amyloid ox-tox transducers.

PMID- 8751435
TI  - Brain cannabinoids in chocolate.

PMID- 8751436
TI  - Transcriptional activation by BRCA1.

PMID- 8751437
TI  - Classic clues to NSF function.

PMID- 8751438
TI  - RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease.
AB  - Amyloid-beta peptide is central to the pathology of Alzheimer's disease, because
      it is neurotoxic--directly by inducing oxidant stress, and indirectly by
      activating microglia. A specific cell-surface acceptor site that could focus its
      effects on target cells has been postulated but not identified. Here we present
      evidence that the 'receptor for advanced glycation end products' (RAGE) is such a
      receptor, and that it mediates effects of the peptide on neurons and microglia.
      Increased expressing of RAGE in Alzheimer's disease brain indicates that it is
      relevant to the pathogenesis of neuronal dysfunction and death.

PMID- 8751439
TI  - A chemical-detecting system based on a cross-reactive optical sensor array.
AB  - The vertebrate olfactory system has long been recognized for its extraordinary
      sensitivity and selectivity for odours. Chemical sensors have been developed
      recently that are based on analogous distributed sensing properties, but although
      an association between artificial devices and the olfactory system has been made
      explicit in some previous studies, none has incorporated comparable mechanisms
      into the mode of detection. Here we describe a multi-analyte fibre-optic sensor
      modelled directly on the olfactory system, in the sense that complex, time
      dependent signals from an array of sensors provide a 'signature' of each analyte.
      In our system, polymer-immobilized dye molecules on the fibre tips give different
      fluorescent response patterns (including spectral shifts, intensity changes,
      spectral shape variations and temporal responses) on exposure to organic vapours,
      depending on the physical and chemical nature (for example, polarity, shape and
      size) of both the vapour and the polymer. We use video images of temporal
      responses of the multi-fibre tip as the input signals to train a neural network
      for vapour recognition. The system is able to identify individual vapours at
      different concentrations with great accuracy. 'Artificial noses' such as this
      should have wide potential application, most notably in environmental and medical
      monitoring.

PMID- 8751440
TI  - The PIE-1 protein and germline specification in C. elegans embryos.
AB  - Totipotent germline blastomeres in Caenorhabditis elegans contain, but do not
      respond to, factors that promote somatic differentiation in other embryonic
      cells. Mutations in the maternal gene pie-1 result in the germline blastomeres
      adopting somatic cell fates. Here we show that pie-1 encodes a nuclear protein,
      PIE-1, that is localized to the germline blastomeres throughout early
      development. During division of each germline blastomere, PIE-1 initially
      associates with both centrosomes of the mitotic spindle. However, PIE-1 rapidly
      disappears from the centrosome destined for the somatic daughter, and persists in
      the centrosome of the daughter that becomes the next germline blastomere. The PIE
      1 protein contains potential zinc-finger motifs also found in the mammalian
      growth-factor response protein TIS-11/NUP475 (refs 4-7). The localization and
      genetic properties of pie-1 provide an example of a repressor-based mechanism for
      preserving pluripotency within a stem cell lineage.

PMID- 8751441
TI  - Repression of gene expression in the embryonic germ lineage of C. elegans.
AB  - The distinction between soma and germline was recognized more than a century ago:
      somatic cells form the body of an organism, whereas germ cells serve to produce
      future generations. In Caenorhabditis elegans, the separation of some and
      germline occurs through a series of asymmetrical divisions, in which embryonic
      germline blastomeres divide unequally to produce one somatic daughter and one
      germline daughter. Here we show that after each asymmetrical division,
      embryonically transcribed RNAs are detected in somatic, but not germline,
      blastomeres. This asymmetry depends on the activity of the germline specific
      factor, PIE-1. In the absence of PIE-1, embryonically transcribed RNAs are
      detected in both somatic and germline blastomeres. Furthermore, ectopic
      expression of PIE-1 in somatic blastomeres can significantly reduce the
      accumulation of new transcripts in these cells. Taken together, these results
      suggest that germ-cell fate depends on an inhibitory mechanism that blocks new
      gene expression in the early embryonic germ lineage.

PMID- 8751442
TI  - Scavenger receptor-mediated adhesion of microglia to beta-amyloid fibrils.
AB  - A pathological hallmark of Alzheimer's disease is the senile plaque, containing
      beta-amyloid fibrils, microglia and astrocytes. Beta-amyloid fibrils exert a
      cytotoxic effect on neurons, and stimulate microglia to produce neurotoxins, such
      as reactive oxygen species. Mononuclear phagocytes, including microglia, express
      scavenger receptors that mediate endocytosis of oxidized low-density
      lipoproteins, and adhesion to glucose-modified extra-cellular matrix proteins.
      Here we report that class A scavenger receptors mediate adhesion of rodent
      microglia and human monocytes to beta-amyloid fibril-coated surfaces leading to
      secretion of reactive oxygen species and cell immobilization. Thus, class A
      scavenger receptors are potential therapeutic targets in Alzheimer's disease.

PMID- 8751443
TI  - Functional coupling between ryanodine receptors and L-type calcium channels in
      neurons.
AB  - In skeletal muscle, L-type Ca2+ channels act as voltage sensors to control
      ryanodine-sensitive Ca2+ channels in the sarcoplasmic reticulum. It has recently
      been demonstrated that these ryanodine receptors generate a retrograde signal
      that modifies L-type Ca2+ -channel activity. Here we demonstrate a tight
      functional coupling between ryanodine receptors and L-type Ca2+ channel in
      neurons. In cerebellar granule cells, activation of the type-1 metabotropic
      glutamate receptor (mGluR1) induced a large, oscillating increase of the L-type
      Ba2+ current. Activation occurred independently of inositol 1,4,5-trisphosphate
      and classical protein kinases, but was mimicked by caffeine and blocked by
      ryanodine. The kinetics of this blockade were dependent on the frequency of Ba2+
      current stimulation. Both mGluR1 and caffeine-induced increase in L-type Ca2+ 
      channel activity persisted in inside-out membrane patches. In these excised
      patches, ryanodine suppressed both the mGluR1- and caffeine-activated L-type Ca2+
      channels. These results demonstrate a novel mechanism for Ca2+ -channel
      modulation in neurons.

PMID- 8751444
TI  - Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of
      the CCR-5 chemokine receptor gene.
AB  - HIV-1 and related viruses require co-receptors, in addition to CD4, to infect
      target cells. The chemokine receptor CCR-5 (ref.1) was recently demonstrated to
      be a co-receptor for macrophage-tropic (M-tropic) HIV-1 strains, and the orphan
      receptor LESTR (also called fusin) allows infection by strains adapted for growth
      in transformed T-cell lines (T-tropic strains). Here we show that a mutant allele
      of CCR-5 is present at a high frequency in caucasian populations (allele
      frequency, 0.092), but is absent in black populations from Western and Central
      Africa and Japanese populations. A 32-base-pair deletion within the coding region
      results in a frame shift, and generates a non-functional receptor that does not
      support membrane fusion or infection by macrophage- and dual-tropic HIV-1
      strains. In a cohort of HIV-1 infected caucasian subjects, no individual
      homozygous for the mutation was found, and the frequency of heterozygotes was 35%
      lower than in the general population. White blood cells from an individual
      homozygous for the null allele were found to be highly resistant to infection by
      M-tropic HIV-1 viruses, confirming that CCR-5 is the major co-receptor for
      primary HIV-1 strains. The lower frequency of heterozygotes in seropositive
      patients may indicate partial resistance.

PMID- 8751445
TI  - Specific cytotoxic T cells eliminate B cells producing virus-neutralizing
      antibodies [corrected].
AB  - In medically important infections with cytopathic viruses, neutralizing
      antibodies are generated within 6-14 days. In contrast, such protective
      antibodies appear late (50-150 days) after infection with immunodeficiency virus
      (HIV) and hepatitis B virus (HBV) in humans, or lymphocytic choriomeningitis
      virus (LCMV) in mice. However, during these infections, non-neutralizing
      antibodies appear much earlier. It has been proposed that T cells suppress
      antibody responses generally and against viruses in vitro. Here we show that the
      suppression of neutralizing-antibody-producing B cells by this non-cytopathic
      virus, and their subsequent destruction by virus-specific cytotoxic T cells. Such
      specific B-cell elimination that leads to a delay in neutralizing-antibody
      production could help to establish persistent virus infections by non-cytopathic
      viruses.

PMID- 8751446
TI  - Deoxycytidyl transferase activity of yeast REV1 protein.
AB  - Mutagenesis induced by DNA damage in Saccharomyces cerevisiae requires the
      products of the REV1, REV3 and REV7 genes. The Rev3 and Rev7 proteins are
      subunits of DNA polymerase-zeta (Pol-zeta), an enzyme whose sole function appears
      to be translesion synthesis. Rev1 protein has weak homology with UmuC protein
      which facilitates translesion synthesis in Escherichia coli by an unknown
      mechanism. We show here that Rev1 protein has a deoxycytidyl transferase activity
      which transfers a dCMP residue from dCTP to the 3' end of a DNA primer in a
      template-dependent reaction. Efficient transfer occurred opposite a template
      abasic site, but approximately 20% transfer also occurred opposite a template
      guanine and approximately 10% opposite adenine or uracil; < or = 1% was seen
      opposite thymine or cytosine. Insertion of cytosine opposite an abasic site
      produced a terminus that was extended efficiently by Pol-zeta, but not by yeast
      Pol-alpha.

PMID- 8751447
TI  - Oxidative DNA damage through long-range electron transfer.
AB  - The possibility has been considered for almost forty years that the DNA double
      helix, which contains a pi-stacked array of heterocyclic base pairs, could be a
      suitable medium for the migration of charge over long molecular distances. This
      notion of high charge mobility is a critical consideration with respect to DNA
      damage. We have previously found that the DNA double helix can serve as a
      molecular bridge for photo-induced electron transfer between
      metallointercalators, with fast rates (> or = 10(10)s-1) and with quenching over
      a long distance (>40 A). Here we use a metallointercalator to introduce a
      photoexcited hole into the DNA pi-stack at a specific site in order to evaluate
      oxidative damage to DNA from a distance. Oligomeric DNA duplexes were prepared
      with a rhodium intercalator covalently attached to one end and separated
      spatially from 5'-GG-3' doublet sites of oxidation. Rhodium-induced photo
      oxidation occurs specifically at the 5'-G in the 5'-GG-3' doublets and is
      observed up to 37 A away from the site of rhodium intercalation. We find that the
      yield of oxidative damage depends sensitively upon oxidation potential and pi
      stacking, but not on distance. These results demonstrate directly that oxidative
      damage to DNA may be promoted from a remote site as a result of hole migration
      through the DNA pi-stack.

PMID- 8751448
TI  - Topology and reorganization of a human TFIID-promoter complex.
AB  - Transcription factor TFIID is a multiprotein complex composed of a TATA-box
      binding subunit, TBP, and several tightly associated factors (TAFs). Human TFIID
      promoter interactions are restricted to the TATA-box region on most core
      promoters but extend over a large promoter region downstream of the TATA box and
      the transcription start site on the Ad2ML promoter. TFIID downstream interactions
      are thought to be functionally relevant because they can be induced by
      transcriptional activators, which in some cases requires TFIIA, result in
      stabilization of the TFIID-promoter complex, and correlate with increased
      recruitment of the remaining general transcription factors. Here we examine the
      topological organization of human TFIID complexes bound to the Ad2ML promoter.
      Our data provide insight into the relative disposition of DNA and several TFIID
      subunits, as well as evidence for DNA wrapping by TFIID, and suggest a direct
      role of TFIIA in the stable positioning of promoter DNA relative to TAFs.

PMID- 8751449
TI  - A rapid method for determination of Aroclor 1260 in cattle adipose tissue.
AB  - A simple analytical procedure for the determination of Aroclor 1260 in cattle
      adipose tissue is described. The polychlorinated biphenyls residues are extracted
      from the tissue using a soxhlet extractor and the extracts are cleaned up using a
      florisil SEP-PAK cartridge. The residues are detected using a gas chromatograph
      equipped with an electron capture detector. The effect of extraction time of the
      Aroclor 1260 residues from the tissue has been investigated and a period of four
      hours is found to give satisfactory percent recoveries. Greater than 85 percent
      recoveries were obtained from adipose tissue spiked with Aroclor 1260. The method
      can be used to detect Aroclor 1260 residue levels as low as 0.10 parts per
      million. The method was used to analyze thirty-one cattle adipose tissue samples
      out of which twenty-six samples were taken from cattle suspected of exposure to a
      pasture containing electrical transformers and capacitors containing Aroclor
      1260. Five control samples were collected from cattle with no known exposure. All
      twenty-six samples were found to contain non-detectable Aroclor 1260 residues.

PMID- 8751450
TI  - Fate and residues of 14C-chloramphenicol in laying chickens.
AB  - Studies were conducted to determine the metabolic fate of chloramphenicol (CAP)
      in White Leghorn using the 14C-labelled compound. In one experiment birds were
      administered orally via intra-crop, a single dose of 100 mg (equivalent to 66 mg
      kg-1 body weight) of CAP containing 14 microCi 14C-CAP, and its absorption,
      elimination and distribution in plasma were recorded. Orally dosed 14C-compound
      was rapidly absorbed, efficiently distributed in plasma and eliminated in excreta
      (> 70% in 5 hr). After 5 h, CAP equivalent residues in issues were lower than 15
      micrograms g-1 for this treatment. In a second experiment birds were given intra
      crop dose of either 0.5 or 5 mg of CAP (each dose contained 2.5 microCi 14C-CAP)
      daily for five consecutive days followed by a seven day withdrawal period and
      elimination of 14C in excreta and eggs was monitored. More than 95% of the
      administered 14C was eliminated within the first 24 h after dosing. Radiocarbon
      (14C) was deposited preferentially in yolks compared to albumen or other tissues.
      Residues declined when feeding was stopped. Various metabolites were isolated and
      identified by a combination of TLC, LC, and LC-MS. The main metabolic route of
      CAP in laying hens appears to be the glucuronidation. Cleavage of the
      dichloroacetate moiety was only a minor route.

PMID- 8751451
TI  - A study on the effect of deoxynivalenol on serotonin receptor binding in pig
      brain membranes.
AB  - Central serotoninergic (5-hydroxytryptamine, 5HT) pathways are believed to be
      involved in the mechanisms of anorexia and/or emesis evoked by the trichothecene
      mycotoxin deoxynivalenol (DON). Using an in vitro membrane receptor binding
      assay, the competitive potency of DON was investigated against several
      radioactive ligands that have a high affinity for selective 5HT receptor
      subgroups. Receptor site densities and displacement profiles in twelve selected
      regions of pig brain were investigated. Overall, DON possessed only minimal
      efficacy to competently block any of the 5HT-ligands tested. IC50 values (50%
      inhibitory concentration) of at least 5 mM DON were required to inhibit binding,
      and in certain regions concentrations of 100 mM were ineffective. In comparison,
      several standard 5HT-antagonists showed 10(3)-10(5) times greater capability than
      DON to displace binding of these ligands. Because these results indicated DON
      possesses only weak affinity for the 5HT-receptor subtypes investigated here,
      this suggested that in vivo, unless relatively high concentrations of the toxin
      are present, its pharmacological effects may be mediated by mechanisms other than
      a functional interaction with serotoninergic receptors at the central level.

PMID- 8751452
TI  - The other side of affirmative action: reactions of nonbeneficiaries to sex-based
      preferential selection.
AB  - Researchers studied 162 male undergraduates in an experiment designed to
      investigate how the experience of unfair treatment affects the reactions of
      nonbeneficiaries of sex-based preferential selection in terms of responses to the
      work task, characterizations of the woman beneficiary, and prosocial orientation
      to the work setting. The basis of selection (merit or preference), the
      comparative ability of the participant and the selectee (superior, inferior,
      equal, or unknown) and the presence or absence of one type of explanatory
      justification for the selection decision (an ideological account) were
      systematically varied. Results indicated that preferential selection can produce
      negative reactions on the part of nonbeneficiaries. However, reactions to
      preferential selection were not always uniform, and procedural and distributive
      aspects of unfairness concerns were found to have consequences for different
      types of nonbeneficiary reactions. In addition, the mitigating effects of the
      ideological account were found to be limited to situations in which the
      beneficiary and nonbeneficiary were believed to be equally qualified.

PMID- 8751453
TI  - A new look at psychological climate and its relationship to job involvement,
      effort, and performance.
AB  - This study investigated the process by which employee perceptions of the
      organizational environment are related to job involvement, effort, and
      performance. The researchers developed an operational definition of psychological
      climate that was based on how employees perceive aspects of the organizational
      environment and interpret them in relation to their own well-being. Perceived
      psychological climate was then related to job involvement, effort, and
      performance in a path-analytic framework. Results showed that perceptions of a
      motivating and involving psychological climate were related to job involvement,
      which in turn was related to effort. Effort was also related to work performance.
      Results revealed that a modest but statistically significant effect of job
      involvement on performance became nonsignificant when effort was inserted into
      the model, indicating the mediating effect of effort on the relationship. The
      results cross-validated well across 2 samples of outside salespeople, indicating
      that relationships are generalizable across these different sales contexts.

PMID- 8751454
TI  - The evaluation gap in performance perceptions: illusory perceptions of groups and
      individuals.
AB  - Four laboratory studies documented systematic performance illusions for
      individuals and group members. After completing a task, most individuals
      typically rank their performance below the median (a negative performance
      illusion) and most group members rank their group performance above the median (a
      positive performance illusion). This evaluation gap surfaced in all studies;
      group members consistently assign their group a higher rank than individuals
      assign themselves. This gap contradicts a number of theories assuming that group
      biases merely extend individual biases.

PMID- 8751455
TI  - Meta-analysis of the relationships between Kerr and Jermier's substitutes for
      leadership and employee job attitudes, role perceptions, and performance.
AB  - A meta-analysis was conducted to estimate more accurately the bivariate
      relationships between leadership behaviors, substitutes for leadership, and
      subordinate attitudes, and role perceptions and performance, and to examine the
      relative strengths of the relationships between these variables. Estimates of 435
      relationships were obtained from 22 studies containing 36 independent samples.
      The findings showed that the combination of the substitutes variables and leader
      behaviors account for a majority of the variance in employee attitudes and role
      perceptions and a substantial proportion of the variance in in-role and extra
      role performance; on average, the substitutes for leadership uniquely accounted
      for more of the variance in the criterion variables than did leader behaviors.

PMID- 8751456
TI  - Effects of preparatory information on enhancing performance under stress.
AB  - Research conducted largely in medical and clinical settings suggests that
      receiving preparatory information prior to a stressful event can reduce negative
      responses to stress. Although results within this domain have been promising,
      little research has examined the efficacy of preparatory information on enhancing
      performance in a more applied task environment. This study examined the effect of
      preparatory information on reducing stress reactions and enhancing performance on
      a realistic decision-making task. Results indicated that those who received
      preparatory information prior to performing under high-stress conditions reported
      less anxiety, were more confident in their ability to perform the task, and made
      fewer performance errors than those who received no preparatory information.

PMID- 8751457
TI  - Thrombopoietin: expression of its receptor MPL and proliferative effects on
      leukemic cells.
AB  - The survival, proliferation, differentiation and function of normal hematopoietic
      cells are negatively and positively controlled by various cytokines. Survival and
      proliferation of leukemic cells appears to be influenced, at least in vitro, by
      several cytokines. Among the different hematopoietic cell lineages,
      megakaryocytopoiesis represents a complex and unique hematopoietic system that is
      thought to be supported by some well-known cytokines; however, the hypothetical
      lineage-specific main regulator of platelet production, termed thrombopoietin
      (TPO) had remained elusive. Recently, characterization of the proto-oncogene c
      mpl revealed structural homology with the hematopoietic cytokine receptor
      superfamily, specific expression on cells of the megakaryocytic lineage and
      functional involvement in megakaryocytopoiesis. Several groups purified and
      cloned the MPL ligand. Extensive in vitro and in vivo studies have shown that the
      MPL ligand has activity in stimulating both megakaryocytopoiesis and platelet
      production proving that this ligand is the long-sought growth factor TPO itself.
      The MPL receptor was found at the mRNA and/or protein level in 40-80% of primary
      acute myeloid leukemia (AML) cases in various series. MPL expression was not
      limited to certain morphological FAB types, although the highest percentages were
      seen in the M6 (erythroid) and M7 (megakaryocytic) subclasses. Among the
      myelodysplastic syndromes (MDS), MPL expression was detected in one third of the
      cases, in particular in refractory anemia with excess of blasts and chronic
      myelomonocytic leukemia. Lymphoid malignancies such as acute lymphoblastic
      leukemia (ALL), non-Hodgkin's lymphoma (NHL) and myeloma were MPL-negative. Among
      the large panel of human leukemia-lymphoma cell lines studied, MPL expression
      occurred predominantly in lines with erythro-megakaryocytic phenotypes. Nearly
      all primary and continuously cultured non-hematopoietic solid tumor samples were
      negative for MPL expression. A significant portion of AML cases and of erythroid,
      megakaryocytic and myeloid leukemia cell lines co-expressed TPO and MPL mRNA
      transcripts, although no biologically active TPO appeared to be secreted by these
      cells. In several studies TPO induced in vitro proliferation of 14-37% of primary
      AML cases, predominantly of the M2 and M7 subtypes. TPO significantly enhanced
      the cytokine-induced growth of AML cells in a substantial fraction of cases
      responsive to GM-CSF, IL-3, IL-6 or SCF. While none of 30 growth factor
      independent erythro-megakaryocytic leukemia cell lines responded to TPO with
      increased proliferation, TPO strongly augmented the growth of several
      constitutively cytokine-dependent cell lines (eg HU-3, M-07e, TF-1) which can be
      made TPO-dependent and used as bioassays. Neither in primary cells nor in cell
      lines did TPO appear to induce any signs of morphological, functional or
      immunological differentiation. Expression of the MPL receptor is not correlated
      with a proliferative response to TPO. In summary, extensive studies on normal
      human and animal cells demonstrated the specificity and function of the MPL
      receptor and proved that its ligand TPO is the major physiological regulator of
      megakaryocytopoiesis. The data reviewed here document the wide expression of the
      MPL receptor on AML cells and also suggest some proliferative effects on certain
      leukemia cells, apparently on non-megakaryocytic AML cells as well. Thus,
      experimental evidence supports the notion that TPO may contribute, at least in
      part, to leukemogenesis, especially in combination with other hematopoietic
      cytokines which is of clinical significance. TPO-responsive cell lines represent
      powerful tools for such analyses.

PMID- 8751458
TI  - The role of intracellular signalling pathways regulating thymocyte and leukemic T
      cell apoptosis.
AB  - Apoptosis plays a critical role during T cell development, both in the generation
      of functionally competent T cells in the thymus and the regulation of peripheral
      T cell populations. The fate of any T cell, whether it is developing in the
      thymus, or functioning in the peripheral immune system, is dependent on T cell
      receptor (TCR) specificity for antigens presented by MHC molecules and on the
      consequences of TCR-generated intracellular signalling pathways which lead to
      activation, anergy or apoptosis. This review describes data that have elucidated
      the way in which these highly regulated TCR-derived signalling pathways lead to
      such diverse final outcomes in thymocytes. Contributions to the induction of
      apoptosis in thymocytes by signalling pathways and receptors such as Fas, CD45
      and CD28 are summarized, particularly with regard to the analysis of relevant
      transgenic mice. Developments concerning regulation of apoptosis by bcl-2 family
      members and the possible effectors of apoptosis, proteases, are assessed.
      Finally, this information is contrasted with the relatively scarce data on
      signalling pathways in thymic-derived T-ALL cells together with potential
      explanations of how transformation might occur by perturbation of apoptotic
      mechanisms. Precise understanding of these pathways may lead to the development
      of novel therapeutic reagents.

PMID- 8751459
TI  - c-kit ligand stimulates tyrosine phosphorylation of the c-Cbl protein in human
      hematopoietic cells.
AB  - c-kit ligand (KL) is a hematopoietic growth factor that plays a major role in the
      survival, expansion and differentiation of hematopoietic progenitor cells of
      various lineages. The biological actions elicited by KL are initiated by binding
      to its cognate receptor, c-kit, which is a transmembrane tyrosine kinase. The
      resulting ligand/receptor complex rapidly activates the intrinsic kit receptor
      tyrosine kinase and subsequent phosphorylation of specific intracellular
      substrates that are involved in downstream signaling events. In the present
      studies, we demonstrate that KL stimulates the rapid tyrosine phosphorylation of
      the proto-oncogene, c-Cbl, in two KL-responsive human hematopoietic cell lines,
      MO7e and TF-1. In both these cell lines we found a constitutive in vivo
      association between c-Cbl and the adaptor protein Grb2 and demonstrate (in vitro)
      that c-Cbl binds primarily to the N-terminal SH3 domain of Grb2. Furthermore, the
      stoichiometry of this association was not significantly affected upon c-kit
      receptor activation. We also provide evidence that c-Cbl is not stably associated
      with the kit receptor either prior to or following KL stimulation. Our findings
      suggest that c-Cbl is an important component in the KL signaling pathway in human
      hematopoietic progenitor cells.

PMID- 8751460
TI  - Outcome of patients with acute myeloid leukemia who failed to respond to a single
      course of first-line induction therapy: a GIMEMA study of 218 unselected
      consecutive patients. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto.
AB  - The outcome of a cohort of 218 consecutive patients who failed to respond to a
      single course of standard daunorubicin plus ARAC (three + seven) induction
      regimen has been retrospectively evaluated to assess the characteristics of this
      group of AML patients and the effectiveness of second-line induction programs.
      Seventy-four of the 218 patients (33.9%) attained complete remission with salvage
      chemotherapies. The multivariate analysis of pretherapy characteristics of the
      patients showed that peroxidase positivity and age were the most important
      factors in determining whether or not the patient would have a favorable response
      to second-line induction regimen. In addition, comparison of marrow
      characteristics at diagnosis with those of marrow after the first-line therapy
      (marrow leukemic index, MLI) provided the greatest differences between second
      line CR and resistant patients. Finally, peroxidase positivity and MLI predicted
      for remission duration and overall survival. Allogeneic BMT, however, appeared
      the most important factor for survival and event-free survival of remitting
      patients. These results are of importance when considering that better defined
      prognostic factors provide an objective rationale for selecting appropriate
      strategies for the treatment of patients who do not respond to a single course of
      induction regimen.

PMID- 8751461
TI  - Isochromosome 7q and trisomy 8 are consistent primary, non-random chromosomal
      abnormalities associated with hepatosplenic T gamma/delta lymphoma.
AB  - Four patients with hepatosplenic T gamma/delta lymphoma, a rare but distinct
      entity of peripheral T cell lymphoma, are reported on. In each case, cytogenetic
      studies showed the presence of an Isochromosome 7q and a trisomy 8. A few
      chromosome studies have previously been reported in this lymphoma subtype but
      comparison with these published cases confirms that isochromosome 7q and trisomy
      8 are primary, non-random chromosomal abnormalities in hepatosplenic T
      gamma/delta lymphoma.

PMID- 8751462
TI  - Lack of TEL-AML1 fusion transcript resulting from a cryptic t(12;21) in adult B
      lineage acute lymphoblastic leukemia in Taiwan.
AB  - Cryptic t(12;21)(p12-13;q22) leading to TEL-AML1 fusion has recently been
      recognized as the most frequent genetic rearrangement in childhood acute
      lymphoblastic leukemia (ALL) in Western countries. More recently, we found a
      similar frequency of this abnormality in Chinese children with ALL in Taiwan. In
      this study, we assessed further the frequency of TEL-AML1 fusion as well as that
      of BCR-ABL in Chinese adults with ALL, using reverse transcriptase-polymerase
      chain reaction assays. Among the 81 cases with newly diagnosed B lineage ALL
      studied, none had the TEL-AML1 fusion whereas 30 had the BCR-ABL fusion. The lack
      of cases with the TEL-AML1 fusion together with the high frequency of BCR-ABL
      fusion could largely account for the poorer outcome of adult ALL as compared with
      childhood ALL.

PMID- 8751463
TI  - Simple method for detection of MYH11 DNA rearrangements in patients with
      inv(16)(p13q22) and acute myeloid leukemia.
AB  - The pericentric inversion on chromosome 16 [inv(16)(p13q22)] and related
      t(16;16)(p13;q22) are recurrent aberrations associated with acute myeloid
      leukemia (AML) M4 Eo. Both abberations result in a fusion of the core binding
      factor beta (CBFB) and smooth muscle myosin heavy chain gene (MYH11). A selected
      genomic 6.9-kb BamHl probe detects MYH11 DNA rearrangements in 18 of 19
      inv(16)/t(16;16) patients tested using HindIII digested DNA. The rearranged
      fragments were not detectable after remission in two cases tested, while they
      were present after relapse in one of these two cases tested.

PMID- 8751464
TI  - Detection and quantification of TEL/AML1 fusion transcripts by polymerase chain
      reaction in childhood acute lymphoblastic leukemia.
AB  - We investigated TEL/AML1 fusion mRNA in 108 children with acute lymphoblastic
      leukemia (ALL) (86 B-lineage ALL, 15 T-ALL, two mixed lineage ALL, and five other
      phenotypes) using reverse transcriptase-polymerase chain reaction (RT-PCR).
      TEL/AML1 transcripts were found in 14 patients (13%) including three relapsed
      patients, and were unexceptionally limited to B-lineage ALL patients. The
      incidence of TEL/AML1 transcripts among B-lineage ALL was 16% (14/86). The
      reciprocal AML1/TEL transcripts were detected in 12 (86%) of the 14 cases
      expressing a TEL/AML1 transcript. In three cases, the TEL gene was fused to exon
      3 of the AML1 gene, and to exon 2 in the remaining cases. To evaluate the amount
      of TEL/AML1 molecules for the quantification of a minimal residual disease (MRD),
      a plasmid vector which contained either a long TEL/AML1 PCR product (464 bp) or a
      short one (425 bp) was used as a competitor. We amplified RNAs obtained from bone
      marrow (BM) at complete remission or from peripheral blood stem cell (PBSC)
      harvests in two representative cases. For one PBSC harvest showing a positive
      result, a competitive PCR was carried out to quantify the amount of MRD. A 1:4
      dilution series of competitor vectors was constructed, and each vector was added
      to a PCR reaction which contain a constant amount of cDNA obtained from the PBSC
      harvest. An equivalent point was compared to that of corresponding samples at
      diagnosis. Using this method, MRD in the PBSC harvest was 3.9:10(3). Our results
      elucidated the incidence, lineage-specificity, and variant forms of TEL/AML1
      fusion transcripts in childhood ALL. Since the percentage of other chromosomal
      translocations in childhood ALL is not more than 5%, TEL/AML1 transcript would be
      the most feasible clone-specific marker for these patients. In addition, our
      method could be a powerful tool for quantification of the TEL/AML1 transcript and
      for the detection of MRD.

PMID- 8751465
TI  - Clonal evolution of immunoglobulin heavy chain rearrangements in childhood B
      precursor acute lymphoblastic leukemia after engraftment in SCID mice.
AB  - We grafted childhood B-precursor acute lymphoblastic leukemia (ALL) bone marrow
      (BM) cells into mice with severe combined immunodeficiency (SCID), in order to
      study the clonal evolution of immunoglobulin heavy chain (IgH) rearrangements in
      the absence of selective pressure by chemotherapy. BM cells from nine patients
      (six diagnosis samples and three relapse samples) were intravenously injected
      into SCID mice (three mice for each patient). All mice injected with cells from
      four patients developed a leukemia-like illness 12-40 weeks after injection. By
      PCR, new subclones that were the result of ongoing IgH rearrangement according to
      the mechanism operative in the injected cell populations (VH-replacement or VH to
      D-JH joining) were detected in the engrafted cell populations for all four
      patients. Subclones were mouse-specific, suggesting that subclone formation is a
      continuous process. Southern analysis after engraftment was unaltered as compared
      to the injected cells for one patient and revealed changes indicative of altered
      clonal composition for three patients. For two patients the observed changes
      possibly reflect the initial engraftment of a limited number of cells and
      occurred without changes in other parameters of the engrafted cell population,
      such as time needed for the development of leukemia, macroscopic organ
      involvement, immunophenotype and S-phase fraction. In one patient, we
      demonstrated the selective outgrowth of only a single cell type present at
      diagnosis, as characterized by IgH rearrangements. Our data show that evolution
      of clonal IgH rearrangements in B-precursor ALL may occur without the selective
      pressure of chemotherapy. Additionally, in some patients subclones present at
      diagnosis, as defined by IgH rearrangements, also possess different biological
      properties.

PMID- 8751466
TI  - The gene product of CBFB-MYH11.
AB  - The inversion(16)(p13;q22) gives rise to chimeric transcripts CBFB-MYH11. To date
      however, no reports have described the full length coding sequence cloned from
      patient material or the protein product derived from transcripts. We describe
      here the cloning and sequencing of the coding region of the fusion gene (type A)
      from patient cells. The sequence is identical to the included portions of the
      normal constituent transcripts. We report the study of CBFB and CBFB-MYH11
      protein using two anti-CBFB antisera. Twenty-two cases of inv(16) leukemia and a
      number of other cases of AML were examined. The predicted 70 kDa type A or 95 kDa
      type D CBFB-MYH11 peptide was detected in 20/22 cases of inv(16) AML. CBFB was
      expressed as a 21 kDa protein in all samples studied, including hematopoietic
      cell lines of all major lineages.

PMID- 8751467
TI  - A low rate of loss of heterozygosity is found at many different loci in childhood
      B-lineage acute lymphocytic leukemia.
AB  - We have carried out a screening for loss of heterozygosity (LOH) in 51 children
      with B-lineage acute lymphoblastic leukemia (ALL). Forty-six highly polymorphic
      microsatellite markers located in subtelomeric areas of every chromosome arm were
      analyzed in each patient. Allelic losses were encountered at 21 of the 46 loci
      tested (46%). The frequency of LOH at a given locus was usually < 10% and
      fractional allelic loss, calculated as the ratio of chromosomal arms displaying
      loss among all informative arms for each patient, ranged from 0.025 to 0.31
      (mean, 0.063). This study provides further evidence that deletional events are a
      major type of genetic alteration found in childhood ALL. The diversity of the
      loci displaying LOH suggests that, as in solid tumors, numerous tumor suppressor
      genes are likely to participate in leukemogenesis. However, the overall low
      frequency of LOH, as well as the absence of microsatellite instability suggest
      that the genetic instability is lower in childhood ALL than in most of the solid
      tumors.

PMID- 8751469
TI  - Effects of interleukin-13 on cytokine secretion by human acute myelogenous
      leukemia blasts.
AB  - Blast cells derived from patients with acute myelogenous leukemia (AML) were
      cultured in the presence of interleukin-13 (IL-13). IL-13 did not cause
      statistically significant alterations of AML blast proliferation when cells were
      cultured in medium alone or together with IL-4, granulocyte colony-stimulating
      factor and granulocyte-macrophage colony-stimulating factor. In contrast, IL-13
      inhibited constitutive AML blast secretion of IL-1 alpha, IL-1 beta, IL-6, tumor
      necrosis factor alpha, granulocyte colony-stimulating factor and granulocyte
      macrophage colony-stimulating factor. IL-4 caused a similar inhibition of
      constitutive cytokine secretion as IL-13, but IL-13 caused no additive inhibition
      in the presence of IL-4. In contrast to IL-4 which increased AML blast release of
      IL-1 receptor antagonist, IL-13 caused no significant alteration of blast release
      of the receptor antagonist. IL-13 inhibited cytokine secretion also in the
      presence of neutralizing IL-4 and IL-10 antibodies and when AML blasts were
      cultures in serum-free conditions. We conclude that IL-13 has a direct and
      nontoxic inhibitory effect on constitutive AML blast cytokine secretion.

PMID- 8751468
TI  - Heterogeneity of breakpoints at the transcriptional co-activator gene, BOB-1, in
      lymphoproliferative disease.
AB  - Chromosome 11q23 is frequently a site of chromosomal translocation in both acute
      leukemias and chronic lymphoproliferative disorders. In the former, an 8 kb
      region within the MLL gene is consistently involved, whereas in the latter
      breakpoints appear to be heterogeneous. In a B cell acute leukemia cell line with
      t(14;18)(q32.3;q21.3) we have previously demonstrated a reciprocal translocation
      between the LAZ3/BCL6 gene at 3q27 and the B cell specific transcriptional
      coactivator gene BOB-1 at 11q23.1, implicating BOB-1 as a potential proto
      oncogene. To confirm the chromosomal localization of BOB-1 we have mapped it by
      FISH to 11q23.1. It lay immediately telomeric of the ATM gene. We have also
      investigated the frequency of BOB-1 rearrangements in a panel of 32 cell lines
      and 71 patient samples. In one case of T cell prolymphocytic leukemia-a disease
      where 11q23 abnormalities are observed-a chromosomal rearrangement was identified
      3.3-0.9 kb centromeric of the 3' end of the gene. Thus, there is a heterogeneity
      of breakpoints associated with BOB-1 while the frequency of the gene's
      involvement in lymphoproliferative diseases is low.

PMID- 8751470
TI  - Increased levels of interleukin-6 (IL-6) in serum and spontaneous in vitro
      production of IL-6 by lymph node mononuclear cells of patients with angio
      immunoblastic lymphadenopathy with dysproteinemia (AILD), and clinical
      effectiveness of cyclosporin A.
AB  - Serum levels of cytokines and in vitro cytokine production by lymph node
      mononuclear cells (LNMC) were studied in four patients with angio-immunoblastic
      lymphadenopathy with dysproteinemia (AILD) or AILD-type T cell lymphoma. An
      increased level of serum interleukin-6 (IL-6) was detected on initial diagnosis
      in both of two patients examined. Spontaneous production of IL-6 by LNMC was
      detected in all four patients studied. Immunosuppressive therapy with cyclosporin
      A (CsA) was attempted in a 68-year-old man, who was refractory to intensive
      combination chemotherapy. The increased level of IL-6 in this patient decreased
      to normal within 3 weeks of CsA administration and the patient became symptom
      free. One and a half months later, the IL-6 level gradually increased along with
      clinical exacerbation. We also measured serum levels of IL-1 alpha, IL-2, IL-4,
      IFN-alpha, gamma and TNF-alpha in parallel with IL-6, but these factors were only
      sporadically detected. IL-6 production by LNMC was stimulated by IL-2 but
      inhibited by CsA. These observations suggest that IL-6 is one of the important
      cytokines to be involved in the pathophysiology of AILD and CsA is a useful
      reagent for relieving symptoms.

PMID- 8751471
TI  - The complement system is defective in chronic lymphatic leukemia patients and in
      their healthy relatives.
AB  - The present study was aimed at analyzing the existence of an impaired complement
      system in CLL patients. For this purpose, the serum levels of the serum
      complement proteins C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, C9, Factor B and
      properdin were repeatedly evaluated by means of radial immunodiffusion assay in
      26 CLL patients over a period of 2 years. At the time of diagnosis, 18 of the 26
      CLL patients showed low serum levels in at least one of these complement proteins
      as compared to a group of sex- and age-matched healthy subjects (P < 0.0001).
      Complement defects affected either the classical and/or the alternative pathway
      components, and in some case low levels of late components (C5-C9) were also
      observed. A reduced level of properdin was the most frequent abnormality (11/18).
      The presence of such abnormalities were correlated with the stage of the disease,
      and they were found in 100% of the patients (11) in advanced stages (Rai II-IV),
      and in 40% of patients (15) in early stages (0-1) (P < 0.004). Severe infections
      occurred in five patients; four of them were in advanced stages of the disease
      and had decreased levels of at least one complement component, whereas the
      remaining patient was in an early stage and had normal levels of complement
      components. These data support the notion that an impaired complement system
      might be involved in the pathophysiology of CLL and its infectious complications.
      Although more work is needed to sustain this hypothesis, we discuss the
      possibility on the basis of data obtained in the first-degree relatives of CLL
      patients, that in some CLL patients the complement deficit might reflect a
      genetic predisposition.

PMID- 8751472
TI  - Aggressive acute CD3+, CD56- T cell large granular lymphocyte leukemia with two
      stages of maturation arrest.
AB  - In the majority of clonal expansions of CD3+ large granular lymphocytes (LGL),
      referred to as T-LGL leukemia, patients have a chronic disease, often manifested
      by severe neutropenia, rheumatoid arthritis, and mild to moderate splenomegaly.
      The characteristic leukemic phenotype is CD3+, CD8+, CD16+, CD57+ and CD56-. Here
      we report an unusual case of T-LGL (CD3cyt+, CD3surface-, CD16+, CD56-) with
      clinicopathological features (acute presentation, large tumor mass, and systemic
      illness with highLGL counts at diagnosis) similar to those described for patients
      with CD3-natural killer (NK)-LGL leukemia. Two distinct stages of maturation
      arrest were observed: in the lymph node abnormal cells were CD4+, CD8+ whereas
      the majority of circulating leukemic cells expressed only CD8. TCR gamma (TCR
      gamma) gene configuration demonstrated that these originated from the same T cell
      clone, suggesting a maturation process between the two populations, or
      preferential passage of CD8 single positive cells into the blood.

PMID- 8751473
TI  - HL-60 leukemia cells produce an autocatalytically truncated form of matrix
      metalloproteinase-9 with impaired sensitivity to inhibition by tissue inhibitors
      of metalloproteinases.
AB  - 92-kDa type IV collagenase/gelatinase (matrix metalloproteinase-9; MMP-9;
      gelatinase B) expression and secretion has been shown to correlate with the
      invasive and metastatic potential of various malignant cells. MMP activity is
      tightly controlled by specific tissue inhibitors of metalloproteinases (TIMPs).
      We found the leukemic cell line HL-60 constitutively to release a 94-kDa
      gelatinase which we identified as MMP-9 shortened by nine amino acids at its N
      terminal end. An additional gelatinolytic activity was present in small amounts
      and identified as a 63-kDa fragment of MMP-9 generated by autocatalytical
      processing. Both enzymes were identical regarding their N-terminus, indicating C
      terminal truncation for the former. Incubation of cells with phorbol ester
      resulted in elevated amounts of both enzymes in conditioned media and in the
      secretion of TIMP-1. Both gelatinases were shown to be activated by trypsin and
      organomercurials and to possess similar activities towards various substrates.
      However, the 63-kDa enzyme differed from the 94-kDa enzyme in a significantly
      reduced inhibition by recombinant TIMP-1 and TIMP-2. Thus, the 63-kDa fragment of
      MMP-9 once activated may escape the regulatory influence of its specific
      inhibitors and may thereby promote matrix degradation during invasion of leukemic
      cells.

PMID- 8751474
TI  - Control genes in reverse transcriptase-polymerase chain reaction assays.

PMID- 8751475
TI  - TEL/AML1 fusion gene is a rare event in adult acute lymphoblastic leukemia.

PMID- 8751476
TI  - Soluble FAS (CD95) is not elevated in the serum of patients with myeloid
      leukemias, myeloproliferative and myelodysplastic syndromes.
AB  - Soluble receptors have been identified for most members of the TNF-receptor/NGF
      receptor superfamily. CD95 (Fas/Apo-1) is of particular importance, since its
      triggering may induce apoptosis in sensitive cells. Recently, a soluble form of
      the CD95 molecule was described which interacts with the CD95-CD95 ligand death
      pathway. Increased concentrations of soluble CD95 (sCD95) were previously
      detected in some patients with T and B cell leukemias and lymphomas. In the
      present study we investigated sCD95 in the serum of patients with myeloid
      leukemias, myeloproliferative and myelodysplastic syndromes. A total of 72
      patients was studied (29 AML, 17 MDS, 20 CML and six other myeloproliferative
      disorders). In AML with active disease, the levels of sCD95 tended to be
      elevated, but did not correlate with defined clinical or laboratory parameters.
      In the other disorders, the levels of sCD95 were not generally increased,
      although some patients had elevated levels. These data strongly suggest that
      sCD95 in AML patients is not derived from leukemic cells, but is possibly
      secreted or shed from reactive or stromal cells. This hypothesis is also
      supported by a group of eight patients with septicemia but not leukemia who had
      elevated sCD95 (P < 0.05). Furthermore, all three patients with elevated sCD95
      who had undergone chemotherapy for AML had major infections. Taken together, this
      study shows that measuring soluble Fas-receptor in myeloid leukemia is not
      diagnostically useful, but increased sCD95 may be associated with clinical
      complications like septicemias.

PMID- 8751477
TI  - Molecular and biologic characterization of a newly established Philadelphia
      positive acute lymphoblastic leukemia cell line (Z-33) with an autocrine response
      to GM-CSF.
AB  - We have recently established a new Philadelphia chromosome (Ph1)-positive acute
      lymphoblastic leukemia (ALL) cell line, designated Z-33. This line has L2
      morphology, ultrastructural characteristics of lymphoblasts and typical B lineage
      surface markers identical to those observed in the Ph1-positive ALL patient from
      whom the line was derived. In addition, a rearranged immunoglobulin heavy-chain
      gene (JH) band was found in Z-33 cells by Southern blot analysis, confirming B
      cell clonality. Cytogenetic analysis of the cell line revealed
      t(9;22)(q34;q11.2). Polymerase chain reaction (PCR)-amplified cDNA from Z-33
      cells demonstrated an e1-az BCR-ABL junction, and the p190BCR-ABL protein was
      detected in them by the immune complex kinase assay. Z-33 cells produce
      interleukin (IL)-1 beta, IL-6, granulocyte colony-stimulating factor (G-CSF),
      granulocyte-macrophage CSF (GM-CSF), tumor necrosis factor (TNF)-alpha, and
      transforming growth factor (TGF)-beta, Neither IL-1 beta, G-CSF, TNF-alpha, nor
      their corresponding antibodies affected the cell line's growth. In contrast, anti
      GM-CSF neutralizing antibodies suppressed Z-33 colony formation, and GM-CSF
      stimulated it in a dose-dependent fashion. In addition, receptor studies with
      biotinylated GM-CSF demonstrated specific binding to Z-33 cells, indicating that
      the cells express GM-CSF receptors. Taken together, our data suggest that the Ph1
      positive Z-33 ALL cells produce GM-CSF, express GM-CSF receptors, and show an
      autocrine proliferative response to this cytokine.

PMID- 8751478
TI  - Immunophenotypic and molecular genetic characterization of a case of CD8+ B cell
      chronic lymphocytic leukemia.
AB  - We report the case of a patient with chronic B lymphocytic leukemia, with stable
      clinical and hematological conditions in the absence of any treatment. The flow
      cytometry analysis of the patient's cells revealed a CD19+, CD5+, IgM+, IgD+,
      lambda chain-phenotype, along with an unusual expression of CD8 alpha/alpha
      homodimer. B cells did not stain with the anti CD8 beta monoclonal antibody
      T8/2T8 5H7. Molecular biology analyses confirmed the monoclonal rearrangements of
      immunoglobulin heavy and lambda light chain genes in the presence of a germline
      configuration of T cell receptor genes. Moreover, an abnormal configuration of
      the CD8A gene was found in the CD8+B lymphocytic clone. We suggest that the
      aberrant expression of the CD8 gene could be related to its abnormal
      configuration.

PMID- 8751479
TI  - Evidence for immunoglobulin heavy chain variable region gene replacement in a
      patient with B cell chronic lymphocytic leukemia.
AB  - Immunoglobulin heavy chain variable (V) gene replacement is an unusual
      recombinatorial event characterized by rearrangement of a germline V gene to a
      preformed VDJ gene complex. This phenomenon has occasionally been implicated in
      the emergence of clonal subpopulations during the course of acute lymphoblastic
      leukemia; it has also been found in murine precursor B cell lines. V gene
      replacement has never been described in lymphoproliferative disorders
      corresponding to more differentiated stages of B cell ontogeny. The present
      communication provides evidence for the operation of the same mechanism in B cell
      chronic lymphocytic leukemia (B-CLL). Genomic DNA and total cellular RNA
      extracted from peripheral blood mononuclear cells of a 48-year-old female patient
      diagnosed as having typical B-CLL were subjected to polymerase chain reaction
      (PCR) amplification aiming to detect rearranged clonal heavy and light chain
      variable genes (VH and VL, respectively). PCR consistently gave two VH
      amplification products, both at the DNA and the RNA level; similar analysis for
      the VL region revealed the presence of a single rearranged VK gene. Direct
      sequence analysis of the PCR products revealed that, except for a number of
      silent mutations, the single rearranged VK gene was identical to the germline A1
      A17 VK gene. The two rearranged VH gene segments belong to the VHl and VHIII gene
      families and are closely homologous, respectively, to the germline gene segments
      V1-18 and V3-30, which have been shown to be used by autoantibodies. Both
      rearranged VH genes showed identical in-frame D-N-JH junctions and JH gene usage
      (JH5b), whereas the VH-N-D junctions were different. The above findings indicate
      that, during the course of the disease of our patient, VH gene replacement took
      place giving rise to two different clonally related subpopulations. This raises
      the intriguing possibility that the recombinase machinery, which governs Ig
      recombinatorial processes, might be operative even at more advanced stages in B
      cell ontogeny.

PMID- 8751480
TI  - Acquired factor VIII inhibitor at the onset of prolymphocytic leukemia.

PMID- 8751481
TI  - Age distribution of childhood acute lymphoblastic leukemia cases suggests
      etiological clues.

PMID- 8751482
TI  - Peripheral blood identification of neoplastic cells and the tumoral growth
      fraction by double immunocytochemical study in a case of anaplastic CD30-positive
      large cell lymphoma.

PMID- 8751483
TI  - Overexpression of EVI-1 in blast crisis of chronic myeloid leukemia.

PMID- 8751484
TI  - The importance of completeness of revascularization during long-term follow-up
      after coronary artery operations.
AB  - Completeness of revascularization after coronary artery bypass operation has been
      shown to improve short- and medium-term outcome. The purpose of this study was to
      assess the independent contribution of completeness of revascularization to long
      term outcome. A total of 2057 patients with multivessel disease with complete
      revascularization and 803 with incomplete revascularization, mean age 57 +/- 9
      years, was studied. The patient groups were similar except for more prior
      myocardial infarctions, worse left ventricular function, and more three-vessel
      disease in the incomplete revascularization group. Complications of perioperative
      infarction and stroke were not different between those having complete versus
      incomplete revascularization. The hospital death rate for patients having
      complete revascularization during the period of study was 0.7% versus 1.5% for
      those having incomplete revascularization (p = 0.06). Length of hospital stay for
      the two groups of patients also was not different. At late follow-up (mean 11.7
      years for complete and 10.8 years for incomplete) patients who had incomplete
      revascularization had a significantly higher prevalence of recurrent angina.
      Multivariate analysis demonstrated the strongest predictors of incomplete
      revascularization to be number of vessels diseased and left ventricular function
      (ejection fraction). The multivariate correlates of survival were older age, left
      ventricular dysfunction, and completeness of revascularization. Completeness of
      revascularization correlated with improved overall patient survival, as well as
      survival in patients with normal left ventricular function. Furthermore, the
      curves continued to separate over time, such that the difference was greater at 8
      years than at 4 years, although by 12 years the curves started to converge.

PMID- 8751485
TI  - Repairing the degenerative mitral valve: ten- to fifteen-year follow-up.
AB  - From January 1969 to December 1992, mitral valve reconstructive operations were
      performed on 155 patients with degenerative mitral valve disease. There were 102
      male and 53 female patients, with a mean age of 60.5 +/- 9.2 years, a mean
      duration of symptoms of 3.8 +/- 2.7 years, and 34% were in atrial fibrillation.
      All patients were in New York Heart Association functional classes III and IV
      before operation. The degree of mitral regurgitation was severe in 94% and
      moderate in 6%, and 50.9% of patients had moderate to severe impairment of left
      ventricular function. Emergency operation was undertaken in 7.1% of cases; 19% of
      patients underwent additional procedures. All patients had posterior mitral
      leaflet pathology and 19 patients had anterior mitral leaflet pathology. Ring
      annuloplasty was used in only 3% of cases. The operative mortality rate was 3.9%,
      9% of patients had morbid events, and 4.5% of patients had repair failure within
      6 months. All patients have been followed up with serial echocardiography for a
      mean time of 5.2 +/- 0.3 years (range 0.5 to 24 years). Immediately after
      operation, 92.9% had no mitral regurgitation to mild mitral regurgitation. At
      last follow-up, 96.9% had no mitral regurgitation to mild mitral regurgitation by
      echocardiography and 98% of patients were in New York Heart Association
      functional classes I and II. The actuarial survival at 15 years was 46% +/- 11%,
      freedom from reoperation was 84.9% +/- 11%, freedom from infective endocarditis
      was 96.0% +/- 11%, freedom from thromboembolism was 90.4% +/- 11%, and freedom
      from all valve-related events was 36.7% +/- 11%. It is well documented that
      repair of degenerative mitral valves offers excellent short-term and medium long
      term benefits. This series represents the longest follow-up reported outside
      Europe. Our results beyond 10 years support our conclusion that an annuloplasty
      ring is not an absolute prerequisite for achieving successful repair of proven
      durability in most patients with degenerative mitral valve disease.

PMID- 8751486
TI  - Rifampicin antibiotic impregnation of the St. Jude Medical mechanical valve
      sewing ring: a weapon against endocarditis.
AB  - The Dacron sewing ring material of the St. Jude Medical mechanical heart valve
      (St. Jude Medical, Inc., St. Paul, Minn.) was passively impregnated with
      rifampicin (60 mg/ml) both in its unsealed state and after sealing by the methods
      of preclotting in blood, autoclaving in blood, and autoclaving in 20% albumin.
      Antistaphylococcal activity in the Dacron material was assessed immediately after
      rifampicin impregnation and at regular periods up to 5 days after implantation
      into the goat aorta. When the Dacron material had been sealed by autoclaving in
      blood and autoclaving in 20% albumin significant retention of antistaphylococcal
      activity was found after 5 days in vivo. Best results were obtained with the use
      of autoclaved blood (p < 0.05). We also compared these results with those
      obtained from impregnating commercially available gelatin-sealed (Gelseal) and
      collagen-sealed (Hemashield) Dacron material with rifampicin. Although
      antistaphylococcal activity was equivalent immediately after rifampicin
      impregnation, after 4 days in vivo the activity was negligible in Gelseal
      material (p < 0.05) and could not be demonstrated in Hemashield material.
      Rifampicin impregnation of the intact St. Jude Medical mechanical valve sewing
      ring may have an application in the prevention of prosthetic valve endocarditis
      and a clinical protocol is suggested.

PMID- 8751487
TI  - Is internal thoracic artery grafting suitable for a moderately stenotic coronary
      artery?
AB  - Grafting an internal thoracic artery to a coronary artery with moderate stenosis
      remains controversial. Competitive flow from the native coronary artery has been
      proposed as the cause of distal narrowing and ultimate failure of the internal
      thoracic artery graft. We investigated intraoperative phasic blood flow in
      internal thoracic arteries grafted to coronary arteries with various degrees of
      stenosis and the influence of stenosis on postoperative angiographic findings.
      One hundred patients who underwent coronary artery bypass grafting of an internal
      thoracic artery to the left anterior descending coronary artery were divided into
      three groups according to degree of coronary stenosis. Group 1 included 39
      patients who had 75% or less stenosis, group 2 included 34 patients with stenosis
      from 76% to 90%, and group 3 included 27 patients with stenosis greater than 90%.
      Mean flow and peak systolic flow of internal thoracic artery graft in group 1
      were lower than those in group 2 (p < 0.01, p < 0.05). Peak diastolic flow in
      group 1 showed no difference from flows in groups 2 and 3. In eight patients in
      group 1, internal thoracic artery flow showed a predominant diastolic peak with
      characteristic systolic reversal as a result of competitive flow from the native
      coronary artery. Angiography at 1 month showed that the internal thoracic artery
      graft was patent in every case. Relative contributions of native coronary artery
      and internal thoracic artery flow to distal perfusion differed among the three
      groups (p < 0.001). In group 1, 15% of patients showed native-dominant flow, 62%
      showed balanced flow, and 23% showed internal thoracic artery-dependent flow. In
      group 2, 9% of patients showed native-dominant flow, 29% showed balanced flow,
      and 62% showed internal thoracic artery-dependent flow. In group 3, 96% of
      patients showed internal thoracic artery-dependent flow. String sign of the
      internal thoracic artery graft developed in only three patients; in two of these
      patients internal thoracic arteries were grafted to coronary arteries with
      stenosis of 50% or less and in the other patient there was competitive flow from
      a diagonal vein graft. Eleven of 13 internal thoracic arteries grafted to
      coronary arteries with stenosis of 50% or less did not show string sign.
      Competitive flow from a moderately stenotic coronary artery did not predispose
      the patient toward string sign of the internal thoracic artery graft in the
      presence of substantial diastolic internal thoracic artery flow. We conclude that
      internal thoracic artery grafting is acceptable for a moderately stenotic
      coronary artery.

PMID- 8751488
TI  - Surgical prophylaxis of recurrent stroke in patients with patent foramen ovale: a
      pilot study.
AB  - Prevention of recurrent stroke in adults with patent foramen ovale represents a
      therapeutic challenge. Antiplatelet or anticoagulant treatment is widely
      introduced, but its exact indication is not known. In this pilot study, eight men
      and three women with previous ischemic cerebral events underwent direct surgical
      closure of the patent foramen ovale. Mean age was 39.4 (from 30 to 58) years. No
      coexisting cause of stroke was found after extensive investigations, including
      blood and coagulation tests, echocardiography, 24-hour three-lead
      electrocardiographic monitoring, extracranial and transcranial Doppler
      ultrasonography, and cerebral angiography. Criteria for operation also included
      at least two of the following: atrial septal aneurysm, multiple cerebral
      infarcts, a history of multiple cerebral events, and Valsalva strain before
      stroke. Before operation, one patient had two shunts (1 patent foramen ovale, 1
      intrapulmonary shunt). No intraoperative or postoperative complications occurred,
      but a few hours after operation transient arrhythmias developed in two patients
      without atrial fibrillation, hemodynamic instability, or embolism. During a
      median follow-up of 12.2 months, no patient had recurrent stroke. All patients
      prospectively underwent brain magnetic resonance imaging and contrast
      echocardiography with simultaneous transcranial Doppler ultrasonography. A
      residual right-to-left interatrial shunt, smaller than the preoperative one, was
      observed in only one patient, whereas no lesion was seen on magnetic resonance
      imaging. Our study suggests that surgical closure of patent foramen ovale in
      patients with presumed paradoxic embolism is safe, with no recurrent stroke in
      the first year of follow-up. Further studies are needed to evaluate the long-term
      prognosis of patients with versus without operation and to define the role of
      operation as an alternative to prolonged antithrombotic treatment.

PMID- 8751490
TI  - Influence of the size of aortic valve prostheses on hemodynamics and change in
      left ventricular mass: implications for the surgical management of aortic
      stenosis.
AB  - Discussion of aortic valve replacement has primarily concerned the choice between
      tissue and mechanical prostheses. Less emphasis has been placed on prosthesis
      size. Despite technical advances increasing prosthesis orifice area, small valves
      implanted in the unenlarged aortic root may not be significantly less obstructive
      than the stenotic native valves they replace. METHODS: In this work we studied 52
      patients (31 women, 21 men; mean age 59.2 years) in whom valve prostheses sized
      19, 21, 23, or 25 mm (30 bioprostheses and 22 tilting disc valves) had been
      implanted to replace stenotic aortic valves. Most patients with 19 or 21 mm
      prostheses were women. Doppler and conventional echocardiographic studies were
      performed in the 10 days preceding the operation and between 10 and 40 months
      (mean 18 months) after the operation. The patients receiving larger valve sizes
      had significantly larger body surface areas than those receiving smaller valve
      sizes (mainly women). RESULTS: No significant differences were observed between
      preoperative and postoperative diameters or left ventricular systolic function
      parameters, but left ventricular mass and mass index decreased in all four groups
      (albeit nonsignificantly in the 19 mm group, and with less statistical
      significance in the 21 mm group than in the 23 and 25 mm groups). Postoperative
      peak and mean transvalvular pressure drops were significantly greater in the 19
      mm group than in the other groups, and the 21 mm group had significantly greater
      transvalvular pressure drops than the 25 mm group. Postoperative effective valve
      area was significantly smaller in the 19 mm group than in the 21 mm group, and
      significantly smaller in the 21 mm group than in the 23 and 25 mm groups.
      CONCLUSION: We conclude that despite undeniable recent improvements in the design
      of artificial heart valves, 19 mm aortic prostheses continue to create
      significant obstruction of the left ventricular outflow tract and, possibly as a
      consequence of this, fail to bring about significant reduction in left
      ventricular hypertrophy.

PMID- 8751489
TI  - Tissue concentrations of endothelins and functional effects of endothelin
      receptor activation in human arteries and veins.
AB  - In the present study, the tissue content and functional effects of endothelin-1
      and endothelin-3 were examined in human vessels of importance in coronary bypass
      operations. Human coronary arteries (i.e., the left anterior descending coronary
      artery) were obtained from eight cardiac valve donors within 6 hours after death,
      pulmonary arteries were perioperatively obtained from 15 patients operated on
      because of lung tumors, and internal thoracic arteries and great saphenous and
      cephalic veins were obtained at coronary bypass operations from a total of 28
      patients. Endothelin-1 and endothelin-3 content was quantified by
      radioimmunoassay. For functional experiments, the vessels were mounted in organ
      baths for recordings of isometric contractions in response to endothelin-1,
      endothelin-3, and the endothelinA-receptor agonist sarafotoxin 6c. In all vessels
      investigated, the endothelin-1 content was higher than that of endothelin-3. The
      highest levels were found in the left anterior descending coronary artery,
      followed in declining order by the internal thoracic artery, pulmonary artery,
      saphenous vein, and cephalic vein. Endothelin-1 contracted all vessels in a
      concentration-dependent fashion. This effect was enhanced in the left anterior
      descending and internal thoracic arteries by inhibition of nitric oxide and
      prostaglandin formation. The contractile effect was attenuated in a concentration
      dependent fashion in all vessels by incubation with the endothelinA-receptor
      blocker BQ-123. Furthermore, contractions evoked by endothelin-1 in the left
      anterior descending coronary and pulmonary arteries were antagonized by the
      combined endothelinA- and endothelinB-receptor blocker bosentan. Endothelin-3
      contracted the left anterior descending coronary and pulmonary arteries and the
      saphenous vein, but not the internal thoracic artery, in a BQ-123-sensitive
      fashion. However, after inhibition with nitric oxide or prostaglandin, endothelin
      3 also contracted the internal thoracic artery, and the response in the left
      anterior descending coronary artery was enhanced. Sarafotoxin 6c evoked a BQ-123
      sensitive contraction of the left anterior descending coronary artery. It is
      concluded that endothelinA receptors mediate the major portion of the
      vasoconstriction observed on exposure to endothelin-1, endothelin-3, and
      sarafotoxin 6c in the left anterior descending coronary, pulmonary, and internal
      thoracic arteries and the saphenous vein. Furthermore, endothelinB-receptor
      activation, with subsequent formation of nitric oxide or prostaglandin (or both),
      counteracts the vasoconstrictor response to endothelin in the left anterior
      descending coronary and internal thoracic arteries, but not in the pulmonary
      artery or saphenous vein. The present findings therefore suggest that endothelinA
      receptor antagonism might prove beneficial in preventing possible endothelin
      induced coronary graft spasm.

PMID- 8751491
TI  - Donor-specific cellular immune response against human cardiac valve allografts.
AB  - We studied the presence of donor-specific T lymphocytes in explanted human
      cardiac valve allografts in vivo. From five of seven explants we propagated
      lymphocyte cultures in an interleukin-2 conditioned medium. Phenotyping revealed
      the presence of T-cell receptors in more than 95% of the lymphocytes obtained in
      each culture. Donor-specific cytotoxicity was demonstrated in three patients with
      known HLA status of the donor. Cytotoxicity was directed against only HLA class I
      in one patient, and against class I and/or class II in the others. These results
      indicate that donor-specific cellular reactivity can be induced by
      transplantation of human cardiac valve allografts.

PMID- 8751492
TI  - Repair of anterior leaflet prolapse: chordal transfer is superior to chordal
      shortening.
AB  - Several techniques are currently used to repair anterior leaflets with elongated
      or ruptured chordae. To evaluate the efficacy of these techniques, we analyzed
      the case histories of 108 patients operated on from 1989 through 1992 with
      degenerative mitral valve disease and prolapse of the anterior leaflet. The mean
      age was 59 +/- 15 years (range 18 to 87 years) and 74 (69%) were male. METHODS:
      Chordal shortening was performed in 31 (29%) and chordal transfer in 77 (71%) of
      the repairs. Of the transfers, 58 (75%) were from the posterior to the anterior
      leaflet and 16 (21%) were from the secondary to the primary position of the
      anterior leaflet. Three patients had both types of transfers. Seventy-one (66%)
      patients had isolated repairs and the remainder had associated procedures. The
      degree of preoperative mitral regurgitation was 3+ or greater for 107 (99%) of
      the patients, mean 3.4 for shortening and 3.7 for transfer. RESULTS: Four (4.0%)
      hospital deaths occurred, none after isolated repair. Follow-up of hospital
      survivors was 100% complete at a mean of 4.0 years. A total of 421 patient-years
      of follow-up were available for analysis. There were seven late deaths, for a 5
      year actuarial survival of 93%. Eleven patients underwent reoperation for
      recurrent mitral regurgitation. Five-year actuarial freedom from reoperation was
      90%-96% after chordal transfer and 74% after chordal shortening, p = 0.003.
      Independent predictors for reoperation include chordal shortening and
      preoperative New York Heart Association functional class III or IV. The mechanism
      of valve failure in six of seven patients undergoing reoperation after chordal
      shortening was rupture of the previously shortened chordae. CONCLUSIONS: We
      conclude that chordal transfer is superior to chordal shortening, providing a
      more predictable correction of mitral regurgitation and a lower incidence of
      reoperation. Reoperations after chordal shortening are a result of rupture of the
      previously shortened chordae.

PMID- 8751493
TI  - Inhaled nitric oxide improves lung allograft function after prolonged storage.
AB  - Morbidity caused by early allograft dysfunction, manifested by a progressive
      increase in pulmonary vascular resistance and a decrease in oxygenation, remains
      a serious problem in lung transplantation. Inhalation of nitric oxide, an
      essential homeostatic molecule, has been shown to have beneficial effects on a
      variety of acute lung injuries. The purpose of the present study was to
      investigate the effect of inhaled nitric oxide on posttransplant function of
      canine left lung allografts. Fourteen dogs underwent left lung
      allotransplantation. Donors received systemic heparin and prostaglandin E1
      followed by pulmonary artery flush with modified Euro-Collins solution. Donor
      left lungs were stored for 18 hours at 1 degree C and subsequently implanted.
      Immediately after reperfusion, the contralateral right main pulmonary artery and
      bronchus were ligated. The chest was closed and recipients turned to the supine
      position for the 6-hour assessment period. Hemodynamic and arterial and venous
      blood gas analyses were made at 15-minute intervals at an inspired oxygen
      fraction of 1.0 and 5 cm of water positive end-expiratory pressure. Animals were
      killed at the end of the assessment. Allograft myeloperoxidase activity assays
      and wet/dry weight ratios were done. In group I (n = 5), nitric oxide gas was
      administered continuously at concentrations of 60 to 70 ppm before reperfusion
      and throughout the 6-hour assessment period. In group II (n = 5), nitric oxide
      administration was initiated at the same concentration after reperfusion injury
      had developed. Group III animals (n = 4) received no nitric oxide. Significant
      improvement in gas exchange was apparent in group I. At the end of the 6-hour
      assessment period, mean arterial oxygen tension was 253.8 +/- 44.7 mm Hg and
      114.9 +/- 25.5 mm Hg in groups I and III, respectively (p < 0.05). Group II
      animals had no improvement in oxygenation with nitric oxide. Systemic
      hemodynamics were unaffected by nitric oxide. However, an immediate decrease in
      pulmonary vascular resistance was noted. Group I myeloperoxidase activity was
      significantly lower than that in control group III (0.24 +/- 0.06 versus 0.36 +/-
      0.04 units, respectively; p < 0.05).

PMID- 8751494
TI  - Effects of portal venous inoculation with donor splenocytes on lung allograft
      survival in dogs.
AB  - The effects of portal venous inoculation with donor splenocytes on lung allograft
      survival were evaluated in dogs. Within the dose range examined, portal venous
      inoculation with donor splenocytes alone did not affect the graft survival time.
      Although the mean graft survival time was prolonged by FK 506 treatment for 14
      days, the transplanted lungs were rejected within 12 days after termination of FK
      506 administration. However, when the recipients were given portal venous
      inoculation with donor splenocytes at the time of transplantation, the graft
      survival time after termination of FK 506 administration was significantly
      prolongated. In the recipients that received combined therapy of portal venous
      inoculation with donor splenocytes and FK 506 treatment, arterial oxygen tension
      and histologic architecture of the transplanted lungs remained within the normal
      range for a longer period than these measures did in control animals that
      received FK 506 treatment alone. Dose-response experiments revealed that 1 x
      10(8) cells/recipient was most effective in causing prolonged graft survival
      after termination of FK 506 treatment. On the basis of these results,
      perioperative portal venous inoculation with donor splenocytes can enhance the
      immunosuppressive effect of FK 506 in the canine lung transplantation model.

PMID- 8751495
TI  - Safe ex vivo coronary angiography with isosmotic contrast agent.
AB  - Plain-film coronary angiography of the cardiac explant on the operating table
      should be considered when conventional cardiac catheterization is desired but
      unavailable. We compared the effects of three contrast solutions on cold
      preserved, isolated guinea pig hearts. Hearts were excised, perfused for 30
      minutes, and arrested with Plegisol solution at 7 degree C. Twenty minutes after
      arrest, experimental hearts were perfused with one of three solutions:
      hyperosmolar Hexabrix solution (n = 6), hyperosmolar Renografin-76 solution (n =
      6), or diluted, isosmotic Omnipaque solution (n = 8). The hearts were flushed
      with cold Plegisol solution 5 minutes later. Control hearts received no contrast
      during arrest (n = 9). The hearts were reperfused after 1 hour of arrest, and
      coronary blood flow (in millimeters per minute), left ventricular developed
      pressure (in millimeters of mercury), and rate of developed pressure (in
      millimeters of mercury per second) were measured. Endothelium-dependent smooth
      muscle relaxation to bradykinin administration and endothelium-independent
      relaxation to sodium nitroprusside administration were also assessed. No
      significant difference in myocardial or endothelial function was noted between
      control hearts and hearts perfused with Omnipaque solution. Hearts perfused with
      Renografin solution or Hexabrix solution, however, were found to have
      significantly impaired endothelial and myocardial function. We conclude that an
      isosmotic contrast solution should be used for ex vivo coronary angiography in
      cold-preserved hearts to avoid impairment of endothelial and myocardial function.

PMID- 8751496
TI  - T-cell receptor expression in C57BL/6 mice that reject or are rendered tolerant
      to bm1 cardiac grafts.
AB  - To study the molecular immunologic features of allograft rejection and tolerance
      induction by intrathymic pretreatment we developed a murine model of cardiac
      transplantation. In this model the transplant recipient was the C57BL/6 mouse
      with its major histocompatibility phenotype H-2b. Donors of cells for intrathymic
      pretreatment and of hearts for grafting were mice of the bm1 mutation. The bm1
      mutation involves substitution of three amino acids in one of the alpha helixes
      of the class I H-2Kb molecule. Because of the discrete molecular configuration of
      the transplant antigen we hypothesized that there would be limited heterogeneity
      of receptor expression on C57BL/6 T cells responding to bm1 cardiac grafts and
      that intrathymic pretreatment would alter the T-cell repertoire of graft
      recipients by causing elimination of T cells responsible for graft rejection.
      Mice were given 0.3 ml of antilymphocyte serum intraperitoneally and had
      intrathymic injection of 25 x 10(6) bm1 splenocytes 12 to 21 days before
      transplantation with a bm1 cardiac graft. Flow cytometric analysis of lymph node
      and spleen cells was used to study the V beta T-cell repertoire of graft
      recipients. Cells were stained with monoclonal antibodies to CD3 and 13 V beta
      regions (n = 5, each group) of T cells in naive, sensitized, and tolerant
      animals. Untreated C57BL/6 mice (n = 9) rejected bm1 cardiac grafts a mean of
      20.4 days after transplantation. Twelve mice pretreated with antilymphocyte serum
      and intrathymic bm1 cells had permanent graft survival (> 100 days, p < 0.0001).
      Animals treated with antilymphocyte serum alone (n = 5) or pretreated animals
      undergoing third-party BALB/c grafts (n = 4) rejected grafts in the normal time
      frame. There was significant alteration of percentage receptor expression of V
      beta 5.1, 7, 12, 13, and 17a in sensitized and tolerant mice. Of interest, V beta
      7 expression was increased in the sensitized mice (3.8% to 8.3%,p = 0.005) and
      was virtually eliminated in tolerant mice (p = 0.005). In conclusion, these data
      suggest that V beta 7 is a critical receptor in the C57BL/6 response to
      subcutaneous bm1 cardiac grafts. Pretreatment of graft recipients with one dose
      of antilymphocyte serum and intrathymic bm1 cells appears to produce permanent
      tolerance to bm1 grafts with elimination of T cells expressing receptor chain V
      beta 7.

PMID- 8751497
TI  - Split transplantation of the trachea: a new operative procedure for extended
      tracheal resection.
AB  - Before tracheal transplantation can be applied clinically, several problems must
      be solved: immunosuppression, blood supply to grafts, and reliable long-term
      preservation of grafts. We have conducted experiments on tracheal transplantation
      to solve these problems. In the present study, we tried a new operative procedure
      to accomplish reliable revascularization of transplanted tracheal grafts. It has
      been reported that transplantation of a 10-ring length of trachea is difficult
      even with omentopexy. Long tracheal allografts can be transplanted with use of
      direct revascularization, but this technique is extremely troublesome. Thus we
      developed a new operative procedure, "split tracheal transplantation," in which
      grafts are divided at the midportion and covered with omentum, after
      demonstrating that the blood supply to tracheal grafts can be reestablished
      around the suture lines. Two groups of dogs were used. In group A (control, n =
      4), a 10-ring length of trachea was autotransplanted. The anastomotic sites and
      grafts were covered with omental pedicles. In group B (split tracheal
      transplantation, n = 10), tracheal grafts 10 rings long were autotransplanted.
      These grafts were divided at the midportion, a piece of omentum was inserted
      between the two halves, and the midportion was sutured. Grafts were observed
      regularly by bronchoscopy and examined histopathologically after the animals died
      or were killed. In some animals, microangiography of the bronchial circulation
      was done. In the control group, necrosis, stenosis, or malacia of the grafts was
      observed in three of the four animals. In the split transplantation group, all
      animals survived for at least 2 months, all grafts were incorporated, and none
      showed ischemia, stenosis, or malacia. Microscopic examination and
      microangiography revealed that neovascularization of the graft was promoted by
      omentum inserted at the midportion of the graft. Split transplantation of the
      trachea is an easy and reliable way to extend tracheal resection.

PMID- 8751498
TI  - Thoracoscopic laser bullectomy: a prospective study with three-month results.
AB  - One hundred forty-one patients were prospectively enrolled in a study of contact
      tip laser bullectomy at four institutions. Ninety-one have had both preoperative
      and postoperative testing at 3 months. Nonsmoking patients with disabling dyspnea
      at less than 50 yards and with a forced expiratory volume in 1 second of 35% or
      less were enrolled. Testing included formal pulmonary function tests, arterial
      blood gasses, computed tomographic scans, ventilation/perfusion scans,
      echocardiograms, electrocardiograms, 6-minute walk testing, transdiaphragmatic
      pressures, and quality of life and dyspnea index questionnaires. A modest 16%
      improvement was noted in forced expiratory volume in 1 second (0.69 to 0.80 L),
      and there was a 29% improvement in 6-minute walk distances (655.2 to 846.3 feet).
      Oxygen use was completely discontinued in 16%. Risk factors for mortality
      included age, 6-minute walk distances, low diffusing capacity for carbon
      monoxide, high carbon dioxide tension, and high base excess. Minor improvement
      was judged from the dyspnea index and the Medical Outcome Study Short Form-36.
      Preoperative predictors of good outcome included heterogeneous disease, lack of
      carbon dioxide retention, and no emaciation (weight < 40 kg). Comparison of our
      results with those in the literature suggests that the improvement seen with the
      contact neodymium:yttrium-aluminum-garnet laser is not as good as that provided
      by the stapled techniques for volume reduction.

PMID- 8751499
TI  - Hemodynamic alterations in bronchiectasis: a base for a new subclassification of
      the disease.
AB  - On the basis of the morphologic and hemodynamic features in 17 patients with
      bilateral bronchiectasis, a new subclassification is proposed. Accordingly, two
      types of bronchiectasis were recognized: perfused and nonperfused. Whereas
      perfused bronchiectasis has intact pulmonary artery flow and cylindrical
      bronchiectatic changes, the nonperfused type involves an absent pulmonary artery
      flow, retrograde filling of the pulmonary artery through the systemic
      circulation, and cystic bronchiectatic changes. A policy of unilateral resection
      of nonperfused bronchiectasis and preservation of the perfused type was adopted
      in 17 patients with bilateral bronchiectasis during an 8-year period. There were
      9 women and 8 men with an average age of 28.6 +/- 7 years (range 18 to 48 years).
      Fifteen patients had mixed bronchiectasis (perfused type on one side and
      nonperfused on the other side) and two had localized bilateral nonperfused type.
      The average duration of follow-up was 38.3 +/- 24.9 months (range 13 to 111
      months). In the 15 patients with mixed bronchiectasis, excellent (N = 8) or good
      (N = 7) results were achieved in all cases. On the other hand, the two patients
      with bilateral nonperfused bronchiectasis did not benefit from unilateral
      resection. This outcome implies that with perfused bronchiectasis the deranged
      function is likely to resolve with time. In the face of the general criticism of
      the traditional morphologic classification system, the proposed functional
      classification not only reflects the degree of severity of the disease process,
      but also predicts whether the involved lung will have a measure of respiratory
      function with regard to gas exchange. Thus the question of which side to resect
      and which to preserve is defined more precisely.

PMID- 8751500
TI  - Stenting in malignant obstruction of superior vena cava.
AB  - The treatment of patients with malignant superior vena caval obstruction with
      minimal morbidity has been made possible by the recent introduction of expandable
      metal stents as the sole palliative treatment or as an adjunct to other treatment
      modalities. To alleviate the distressing symptoms of superior vena caval
      obstruction, self-expanding metal stents were used successfully in 12 (Wallstent
      device in 6 and Gianturco device in 6 patients) of 13 patients. The diagnoses
      were small cell carcinoma (n = 4), squamous cell carcinoma (n = 4), non-Hodgkin's
      lymphoma (n = 1), and mesothelioma (n = 1), and a diagnosis of malignancy was not
      confirmed (although strongly suspected) in the remaining three cases. Eleven
      patients had immediate relief of obstruction and there was no change in one
      patient. Mean follow-up was 3.7 months (range 1 to 10 months). Excellent
      palliation was obtained in all but one patient in whom recurrent superior vena
      caval obstruction developed 3 months after stenting. Mean survival was 4.8 months
      (range 1 to 10 months). The ease of insertion with the use of local anesthesia
      with radiologic control, the self-expanding nature of the stent, and the lack of
      major complications on follow-up of up to 10 months are particular advantages.
      The self-expanding superior vena caval stents are a useful addition to our
      armamentarium in the management of malignant superior vena caval obstruction.

PMID- 8751501
TI  - Perioperative blood transfusions and decreased long-term survival in esophageal
      cancer.
AB  - We evaluated retrospectively the effect of perioperative blood transfusions on
      survival in esophageal cancer. The records of all patients who underwent
      esophageal resection (n = 316) at UCLA Medical Center from 1970 to 1993 were
      reviewed. Statistical analysis included univariate (log-rank chi 2) and
      multivariate (Cox proportional hazards) analyses with other known risk factors.
      High-volume blood transfusions (> 8 units) but not low-volume blood transfusions
      (1 to 8 units) were associated with a significant decrease in long-term survival
      (median survival: no transfusion, 22 months; low-volume blood transfusion, 14.5
      months, versus high-volume blood transfusions, 6.5 months; p < 0.01).
      Multivariate analysis revealed that the shorter survival with high-volume blood
      transfusions was a result of an increased number of postoperative complications.
      High-volume blood transfusions were not associated with increases in tumor
      recurrence or infectious complications. The association between shorter survival
      and high-volume blood transfusions in esophageal cancer may, therefore, be
      because of the circumstances necessitating transfusion rather than any
      immunosuppressive effects of the transfused blood. These findings suggest that
      the transfusion of blood does not by itself decrease the chance of cure after
      esophageal resection.

PMID- 8751502
TI  - Time trends and survival after operations for primary lung cancer from 1976
      through 1990.
AB  - To assess the time trends and survivals after operations for primary lung cancer,
      the cases of 845 consecutive patients who underwent thoracotomy between 1976 and
      1990 were retrospectively reviewed by groups corresponding to year of the
      operation (the early period was 1976 to 1980, n = 208; the middle period was 1981
      to 1985, n = 291, and the late period was 1986 to 1990, n = 346). The 5-year
      survivals at the early, the middle, and the late periods were 31.5%, 39.0%, and
      54.0%, respectively, with significant improvement particularly at the late period
      (p < 0.05 for the early period vs the middle period, p < 0.01 for the early or
      middle period vs the late period); the improvement was caused by increase in the
      ratio of patients with stage I disease (20.7% at the early period, 32.0% at the
      middle period, 44.2% at the late period), increase in the rates of complete tumor
      resection with lymph node dissection (57.2%, 68.0%, 74.3%, respectively), and
      decrease in the rates of operation-related death (3.8%, 3.4%, 0.9%,
      respectively). The postoperative prognosis of patients with stage II disease at
      the late period (5-year survival 74.8%) showed significant improvement compared
      with the other periods. Moreover, the prognosis of patients with stage IIIa, pN2
      disease (5-year survival 41.5%) showed significant improvement, which was caused
      by the significant decrease in patients with pT3 N2 M0 disease and poor
      prognosis.

PMID- 8751503
TI  - Cost of patient follow-up after potentially curative lung cancer treatment.
AB  - The two objectives of this study were to determine the range of recommended
      follow-up strategies for patients with lung cancer treated with curative intent
      and to estimate the cost of such follow-up. Ten articles delineating eight
      specific follow-up strategies were identified from a Medline search of the
      literature for 1980 through 1995. An economic analysis was done of the costs
      associated with the identified strategies. Charge data obtained from the Part B
      Medicare Annual Data file and the Hospital Outpatient Bill file were used as a
      proxy for cost. Follow-up intensity varied widely across strategies for 5 years
      of posttreatment follow-up. Medicare-allowed charges for 5-year follow-up ranged
      from a low of $946 to a high of $5645. When Medicare-allowed charges were
      converted to a proxy for actual charges by a conversion ratio of 1.62, the range
      was $1533 to $9145, a fivefold difference in charges. There was no indication
      that more intensive, higher-cost strategies increased survival or quality of
      life. The published literature, including textbooks, holds few answers in this
      area.

PMID- 8751504
TI  - Right ventricular ejection fraction in the preoperative risk evaluation of
      candidates for pulmonary resection.
AB  - The major determinants of postoperative morbidity and mortality after lung
      resection are the physiologic and functional statuses of the pulmonary and
      cardiac systems. In our previous study, serial measurements of right ventricular
      performance after pulmonary resection demonstrated significant right ventricular
      dysfunction in the postoperative period. This study evaluates the preoperative
      measurement of right ventricular ejection fraction as a predictor of
      postoperative complications. In addition to conventional cardiopulmonary
      functional tests, right ventricular function was assessed with a thermodilution
      technique at rest and during exercise in 18 patients before and 3 weeks after
      lobectomy or pneumonectomy. The patients were grouped according to severity of
      right ventricular functional defect: right ventricular ejection fraction of at
      least 45% (group Ia, n = 8), right ventricular ejection fraction less than 45%
      (group Ib, n = 10), exercise-induced increases in right ventricular ejection
      fraction (group IIa, n = 8), and exercise-induced decreases in right ventricular
      ejection fraction (group IIb, n = 10). Postoperative cardiopulmonary morbidity
      was recorded for two patients (25%) in group Ia, three patients (30%) in group
      Ib, no patients (0%) in group IIa, and five patients (50%) in group IIb.
      Postoperative hospital stay was 28.9 +/- 8.5 days in group Ia, 29.9 +/- 20.2 days
      in group Ib, 19.4 +/- 8.0 days in group IIa, and 37.5 +/- 15.9 days in group IIb
      (p < 0.05, group IIa vs group IIb). Although resection-induced changes in forced
      expiratory volume in 1 second did not differ significantly between group Ia and
      group Ib, these values appeared to be increased in groups IIa (not statistically
      significant) and IIb (significantly, p < 0.05). The measured postoperative values
      of forced expiratory volume in 1 second and vital capacity were significantly
      higher than the predicted postoperative values (p < 0.05) in group IIa, but not
      in groups Ia, Ib, and IIb. We conclude that evaluation of right ventricular
      performance is useful in determining which patients are at increased risk for
      medical complications after lung resection. Exercise-induced change in right
      ventricular ejection fraction may be a better indicator of high risk among
      candidates for pulmonary resection than the absolute value of this parameter.

PMID- 8751505
TI  - Delayed remission after thymectomy for myasthenia gravis of the purely ocular
      type.
AB  - Twenty-two cases of purely ocular myasthenia gravis were reviewed to evaluate the
      long-term effects of thymectomy. Remission rate increased gradually with time
      (11.8% at 3 years, 23.1% at 5 years, and 33.3% at 10 years). Analysis of factors
      influencing remission with time showed that patients with short duration of
      illness attained remission significantly earlier (p = 0.035 at 5-year follow-up).
      One of 22 patients with purely ocular myasthenia gravis (4.5%) had disease
      progression. Because ocular myasthenia gravis often progresses to the generalized
      type and because duration of illness before operation is one of important factors
      influencing remission, we conclude that thymectomy in the earlier stages of the
      disease is the preferred treatment for ocular myasthenia gravis, just as for
      generalized myasthenia gravis.

PMID- 8751506
TI  - Prognostic factors and long-term results after thymoma resection: a series of 307
      patients.
AB  - Three hundred seven cases of patients who underwent operation for thymoma (196 of
      whom had myasthenia gravis) were analyzed to assess the prognostic values of
      Masaoka clinical staging, completeness of resection, histologic classification,
      history of myasthenia gravis, and postoperative radiotherapy. According to the
      Masaoka staging system, 135 thymomas were stage I, 70 were stage II, 83 were
      stage III, and 19 were stage IV. According to the Verley and Hollmann histologic
      classification system, 67 thymomas were type 1, 77 were type 2, 139 were type 3,
      and 24 were type 4. Two hundred sixty patients underwent complete resection, 30
      underwent incomplete resection, and 17 underwent biopsy. Postoperative
      radiotherapy was performed mainly in cases of invasive or metastatic thymoma.
      Mean follow-up was 8 years; eight patients were unavailable for follow-up. The
      overall 10- and 15-year survivals were 67% and 57%, respectively. In univariate
      analysis, three prognostic factors were established: completeness of resection,
      Masaoka clinical staging, and histologic classification. Furthermore, among
      patients with stage III thymomas, survival was significantly higher for patients
      with complete resection than for patients with incomplete resection (p < 0.001).
      Completeness of resection should therefore be taken into account in clinical
      pathologic staging. We did not find any significant difference with respect to
      disease-free survival between patients who had postoperative radiotherapy and
      those who did not. In multivariate analysis, the sole significant prognostic
      factor was completeness of resection. On the basis of these findings, a new
      clinical-pathologic staging system is proposed.

PMID- 8751507
TI  - Video-assisted thoracoscopic treatment of spontaneous pneumothorax: technique and
      results of one hundred cases.
AB  - OBJECTIVE: This article describes the technique and results for an initial series
      of 100 pneumothoraces treated by video-assisted thoracoscopy. METHODS: From May
      1991 to November 1994, 97 patients (78 male and 19 female patients) aged 37.2 +/-
      17 years (range 14 to 92 years) underwent video-assisted thoracoscopy for
      treatment of spontaneous pneumothorax (primary in 75 patients, secondary in 22
      patients). RESULTS: The procedure was unilateral in 94 patients and bilateral in
      three patients (total 100 cases). Pleural bullae were resected with an endoscopic
      linear stapler; a lung biopsy was performed in the absence of any identifiable
      lesion. Pleurodesis was achieved by electrocoagulation of the pleura (n = 3),
      "patch" pleurectomy (n = 3), subtotal pleurectomy (n = 20), or pleural abrasion
      (n = 74), including conversion to standard thoracotomy in five. One of these five
      patients had primary pneumothorax and four had secondary pneumothorax. There were
      no postoperative deaths. A complication developed in 10 patients: five patients
      with a primary pneumothorax (6.6%) and five with a secondary pneumothorax
      (27.7%). The mean postoperative hospital stay was 8.25 +/- 3.2 days. Mean follow
      up is 30 months (range 7 to 49 months). Pneumothorax recurred in 3% of patients,
      all of whom were operated on at the start of our experience. Three percent of the
      patients had chronic postoperative chest pain. CONCLUSIONS: Video-assisted
      thoracoscopy is a valid alternative to open thoracotomy for the treatment of
      spontaneous primary pneumothorax. Its role for the management of secondary
      pneumothorax remains to be defined. In the long term, the efficacy of video
      assisted thoracoscopic pleurodesis and surgeon experience should yield the same
      results as standard operative therapy.

PMID- 8751508
TI  - Unifocalization for pulmonary atresia with ventricular septal defect and major
      aortopulmonary collateral arteries.
AB  - To extend the indications for corrective operation in patients with pulmonary
      atresia, ventricular septal defect, and major aortopulmonary collateral arteries,
      surgical procedures were done to unify the blood sources for pulmonary perfusion.
      Since December 1985, 50 patients have undergone unifocalization at ages from 2
      months to 26 years with a mean of 6 +/- 7 years. In total, 84 staged
      unifocalization procedures and 5 other palliative procedures were done in 49
      patients. These included several operative procedures: simple ligation of major
      aortopulmonary collateral arteries in 8; pulmonary angioplasty in 29 including
      reconstruction of the pulmonary arterial tree by direct anastomosis or
      interposition between the central pulmonary arteries and the intrapulmonary
      arteries; construction of artificial central pulmonary arteries with use of a
      xenograft pericardial tube graft in 36 with no native central pulmonary arteries
      detected; and construction of supplemental central pulmonary arteries also with
      use of a pericardial tube graft in 10. The pericardial tube graft, if used, was
      anastomosed to the intrapulmonary arteries on one end and connected to a
      prosthetic tube on the other end so as to perfuse the reconstructed pulmonary
      arteries. The anastomosis was made inside the lung through the divided interlobar
      fissure. Five patients died after operation among those undergoing these 89
      preparative operative procedures. Deaths were related either to bleeding caused
      by anticoagulation therapy administered to prevent thrombosis within the
      xenograft pericardial tube graft used or to progressive congestive heart failure
      as a result of an excessive amount of pulmonary blood flow. Twenty-six patients
      have undergone intracardiac repair after previous unifocalization. In 16 patients
      the artificial central pulmonary arteries surgically constructed were connected
      to each other and then an external conduit was placed. In another patient,
      intracardiac repair and unifocalization could be concomitantly achieved via a
      median sternotomy. The right ventricle to left ventricle systolic pressure ratio
      immediately after intracardiac repair in 27 patients ranged from 0.24 to 0.91
      with a mean of 0.54 +/- 0.17. One patient (4%) died shortly after intracardiac
      repair because of thrombosis within the pulmonary arteries. Postoperative
      catheterization showed that pulmonary vascular resistance was correlated
      significantly with the number of pulmonary vascular segments functioning rather
      than with the condition of the central pulmonary arteries. We conclude that
      surgical unifocalization is a feasible procedure before subsequent intracardiac
      repair, even in patients with critically hypoplastic or absent central pulmonary
      arteries.

PMID- 8751509
TI  - Proton magnetic resonance spectroscopy in the evaluation of children with
      congenital heart disease and acute central nervous system injury.
AB  - We studied nine infants and children, aged 1 week to 42 months, with severe acute
      central nervous system injuries associated with cardiac disease or corrective
      operations by means of single-voxel proton magnetic resonance spectroscopy to
      determine whether this technique would be useful in predicting neurologic
      outcome. Proton magnetic resonance spectroscopic data were acquired from the
      occipital gray and parietal white matter (8 cm3 volume, stimulated echo
      acquisition mode sequence with echo time of 20 msec and repetition time of 3.0
      seconds) a median of 9 days after operation (range 3 to 42 days). Data were
      expressed as ratios of areas under metabolite peaks, including N-acetyl
      compounds, choline-containing compounds, creatine and phosphocreatine, and
      lactate. Four patients had cerebral insults before operation, one had both a
      preoperative and a perioperative insult, three had perioperative insults, and one
      had a prolonged cardiac arrest 2 days after operation. Outcomes (Glasgow Outcome
      Scale scores) were assigned at discharge and 6 to 12 months after injury. Six
      patients were in a vegetative state or had severe impairment at discharge, and
      two still had severe impairment at 6- to 12-month follow-up. Proton magnetic
      resonance spectroscopy showed lactate in these two patients, along with markedly
      reduced ratios of N-acetyl compounds to creatine compounds. The other four
      patients with severe impairment recovered to a level of mild disability at follow
      up. Proton magnetic resonance spectroscopy showed no lactate in these four
      patients; however, one patient showed moderately reduced ratio of N-acetyl
      compounds to creatine compounds. The three patients who had mild or moderate
      impairment at discharge showed no lactate and mild or no changes in metabolite
      ratios; follow-up revealed normal or mild outcomes. Overall, we found that the
      presence of lactate and markedly reduced ratios of N-acetyl compounds to creatine
      compounds were predictive of severe outcomes at discharge and long-term follow
      up, whereas no lactate and mild or no changes in ratios suggested potential for
      recovery with at least a mild disability. Continuing investigations are in
      progress to determine the optimal selection of candidates and timing of proton
      magnetic resonance spectroscopic studies.

PMID- 8751510
TI  - Unusual forms of tracheobronchial compression in infants with congenital heart
      disease.
AB  - Three groups of unusual forms of tracheobronchial compression caused by vascular
      anomalies are presented. Three patients had an encircling right aortic arch with
      a left-sided descending aorta and ligamentum arteriosum (group 1), two patients
      had airway compression caused by a pincer effect between a malposed and enlarged
      ascending aorta and the descending aorta (group 2), and three patients had airway
      compression after an arterial switch operation for transposition of the great
      arteries (group 3). Symptoms developed in all patients before the age of 4
      months, and six of them had multiple failed attempts at extubation before the
      surgical intervention directed at relieving the airway compression. Fiberoptic
      endoscopy was used in all patients as a first-line diagnostic tool and was 100%
      accurate in establishing the diagnosis. The operations performed were aortic
      uncrossing in group 1, dissection and aortopexy of the right or left main
      bronchus in group 2, and dissection of the left main bronchus and lysis of
      adhesions in group 3. In group 1 there was one early death, resulting from
      aspiration, and one late death 4 years later, resulting from an unrelated cause.
      In this group, bronchomalacia was noted after the operation and resolved
      gradually in the year after the intervention. In group 2, one patient died of an
      aortobronchial fistula after placement of a bronchial stent. Group 3 patients had
      good postoperative results. Two of them are completely symptom-free and one has
      residual bronchomalacia and may need placement of a bronchial stent.

PMID- 8751511
TI  - Pedicled pericardium for repair of right ventricular outflow tract and pulmonary
      arterial stenoses in tetralogy of Fallot: a six-year experience.
AB  - From June 1988 through June 1994, 20 children with symptomatic tetralogy of
      Fallot, associated with hypoplastic or stenotic pulmonary arteries in 19 cases,
      were operated on in our institution. Mean age at operation was 49.5 +/- 43 months
      (ranging from 10 months to 12.5 years). Mean weight was 13.5 +/- 6.5 kg (range
      6.2 to 30 kg) and mean body surface area was 0.6 +/- 0.2 m2. Mean preoperative
      hematocrit value was 47.6% +/- 11.1%, and mean preoperative arterial oxygen
      saturation ratio was 75.7 +/- 9.5. Six patients (30%) had prior systemic
      pulmonary arterial shunts. Pulmonary arterial stenoses were congenital or
      iatrogenic (or both) and were located principally on the left pulmonary artery
      (63%), on the pulmonary bifurcation (15%), or separately on the left and right
      pulmonary arteries (21%). In all children the pulmonary arterial tree was
      repaired with the patient's own pedicled pericardium. Mean follow-up is 36 +/-
      25.2 months (range 1 to 71 months). Hospital mortality rate was 0%. There was one
      late death, and two children were lost to long-term follow-up. No child required
      reoperation. Seventeen children returned for evaluation, consisting of physical
      examination, electrocardiogram, chest roentgenogram, and Doppler echocardiogram,
      and 11 underwent late catheterization or magnetic resonance imaging of the chest
      to evaluate the pulmonary arterial repair. All children were in New York Heart
      Association class I or II. Right ventricular function was normal by
      echocardiography in 100% with a mean right ventricular systolic pressure of 39.37
      +/- 8.4 mm Hg. Mild to moderate pulmonary regurgitation was present in the
      majority of patients. The results of pulmonary arterial repair were good in 100%.
      There was no residual stenosis, and we observed uniform enlargement of the
      repaired pulmonary arteries over a 5-month to 6-year follow-up period. These
      results are of particular interest inasmuch as other materials previously used
      for repair of pulmonary arteries do not grow and may even shrink, resulting in
      residual stenosis.

PMID- 8751512
TI  - Aortic valve replacement with a pulmonary autograft in infants with critical
      aortic stenosis.
AB  - Seven patients with critical aortic stenosis underwent aortic valve replacement
      with a pulmonary autograft (the Ross operation) between the ages of 5 weeks and 9
      months. The operation was considered mandatory for survival because of continued
      severe heart failure or valve avulsion. Six of the patients had undergone
      unsuccessful previous palliations, such as commissurotomy, balloon dilation, and
      transventricular valvotomy, performed singly (n = 1) or in combination (n = 5).
      The other patient with a severely hypoplastic aortic valve ring underwent the
      Ross procedure as a primary operation. Two operative deaths occurred. In both
      cases severe endocardial fibroelastosis was detected at autopsy. One late death 1
      year after the operation resulted from progressive hypertrophic cardiomyopathy
      and pulmonary hypertension. The rest of the patients are doing well, without
      medications. Apart from trivial regurgitation in two patients, the pulmonary
      autograft is performing well.

PMID- 8751513
TI  - Fetal model of single ventricle physiology: hemodynamic effects of oxygen, nitric
      oxide, carbon dioxide, and hypoxia in the early postnatal period.
AB  - BACKGROUND: In patients with single ventricle physiology, the distribution of
      flow to the systemic and pulmonary circulations, which are in parallel, largely
      depends on the relative resistances in the respective vascular beds. Although
      neonatal palliation in patients with single ventricle physiology has become more
      common, medical management during the perinatal and perioperative periods is
      often based primarily on personal and institutional experience and is complicated
      by the transition to postnatal life and the effects of cardiopulmonary bypass.
      The lack of an animal model that suitably mimics single ventricle physiology has
      impeded progress in this area. OBJECTIVE: The purpose of the current study was to
      investigate the effects of respiratory manipulations on pulmonary hemodynamics in
      the early neonatal period in a reproducible model of single ventricle physiology
      created in utero. METHODS: A 10 mm Damus-Kaye-Stansel aortopulmonary anastomosis
      was created in fetal sheep (n = 14) at 140 +/- 1.2 days' gestation, with
      pulmonary blood flow provided through a 5 mm aortopulmonary shunt after ligation
      of the main pulmonary artery distally. Two to 3 days after delivery at term,
      lambs (n = 11) underwent an open sternotomy and 30 minutes of deep hypothermic
      circulatory arrest. Both before and after bypass, respiratory manipulations,
      including administration of nitric oxide (80 ppm), 100% oxygen, 10% oxygen, and
      5% carbon dioxide, were performed and hemodynamic variables were measured.
      RESULTS: Nitric oxide and oxygen caused a decrease in pulmonary vascular
      resistance and an increase in the pulmonary/systemic blood flow ratio, both
      before and after bypass. Hypoxia and carbon dioxide produced a significant rise
      in pulmonary vascular resistance and a significant drop in the ratio of pulmonary
      to systemic blood flow. CONCLUSIONS: Oxygen, nitric oxide, and carbon dioxide all
      appear to be useful means of manipulating pulmonary vascular resistance and
      pulmonary/systemic blood flow ratio in neonatal lambs with single ventricle
      physiology, but further investigation is necessary to understand their dose
      responsive effects and the effects of prolonged administration.

PMID- 8751515
TI  - Protamine-induced hypotension in heart operations: application of the concept of
      ventricular-arterial coupling.
AB  - Protamine sulfate often causes hypotension during heparin neutralization. The
      concept of ventricular-arterial coupling was applied to determine whether a
      negative inotropic effect or a vasodilating effect of protamine was the major
      contributing factor to this hypotension. Thirty-five patients who underwent
      cardiac operations were studied during operation by measuring instantaneous left
      ventricular pressure and aortic flow to examine the end-systolic pressure-volume
      relationship. We obtained end-systolic elastance and effective arterial elastance
      values in a beat-to-beat fashion with a single-beat estimation method. In 28 of
      the 35 patients (80%), mean arterial pressure decreased more than 10 mm Hg with
      protamine infusion. Parameters were compared at the following three points:
      before a decrease in mean arterial pressure (control), at maximally decreased
      mean arterial pressure (maximum), and at a middle point between control and
      maximum values (midpoint). At both midpoint and maximum, mean arterial pressure
      decreased significantly (control 79.6 +/- 12.6 mm Hg, midpoint 66.5 +/- 10.8 mm
      Hg, maximum 52.7 +/- 9.9 mm Hg; p < 0.01). Similar changes were observed in
      effective arterial elastance (control 2.00 +/- 0.75 mm Hg/ml, midpoint 1.60 +/-
      0.53 mm Hg/ml, maximum 1.31 +/- 0.46 mm Hg/ml; p < 0.01). Although the decrease
      in end-systolic elastance at midpoint (control 3.08 +/- 1.61 mm Hg/ml, midpoint
      2.92 +/- 1.68 mm Hg/ml) did not reach statistical significance, end-systolic
      elastance significantly decreased at maximum (2.63 +/- 1.46 mm Hg/ml; p < 0.01).
      Continuous measurements showed that the decreases in mean arterial pressure and
      effective arterial elastance always preceded the depression of end-systolic
      elastance and that afterload reduction by vasodilating effect of protamine was
      the mechanism most likely to have initiated the hypotension. Delayed decrease in
      contractility may be ascribed to reduced coronary perfusion pressure caused by
      vasodilation or to a direct effect of protamine.

PMID- 8751514
TI  - Changes in autonomic response of the cerebral circulation after normothermic
      extracorporeal circulation.
AB  - Patients who undergo cardiopulmonary bypass frequently have neuropsychologic
      dysfunction. This study was undertaken to determine whether altered cerebral
      perfusion and vascular responses may in part lead to these neuropsychologic
      changes. Pigs were placed on normothermic cardiopulmonary bypass for 2 hours.
      Basal cerebral blood flow and in vivo responses to administration by internal
      carotid artery of neuronally released vasoactive substances were evaluated before
      and 5 to 15 minutes after termination of cardiopulmonary bypass. Another group of
      pigs were placed on cardiopulmonary bypass for 2 hours and then perfused off
      bypass for 1 additional hour. In vitro responses of cerebral arterial
      microvessels (100 to 175 microns) from both groups were examined in a pressurized
      (40 mm Hg) no-flow state with videomicroscopy. Vessels from uninstrumented pigs
      served as control preparations for in vitro studies. Cerebrovascular resistance
      and cerebral perfusion were maintained constant during cardiopulmonary bypass and
      after separation from bypass. The internal carotid artery infusion of
      acetylcholine (cholinergic agonist) caused increased internal carotid artery
      blood flow before cardiopulmonary bypass but decreased blood flow after
      cardiopulmonary bypass. After 2 hours of cardiopulmonary bypass, the increase in
      internal carotid artery blood flow induced by isoproterenol (a beta-adrenoceptor
      agonist) was reduced, whereas the response to sodium nitroprusside (a guanylate
      cyclase activator) was unchanged. In vitro acetylcholine-induced microvascular
      vasodilation was converted to a contractile response and isoproterenol elicited
      less relaxation after 2 hours of cardiopulmonary bypass. One hour of cerebral
      perfusion after cardiopulmonary bypass caused a further reduction in
      isoproterenol-induced relaxation but had no further effect on the cholinergically
      mediated response. In vitro relaxation responses to sodium nitroprusside and
      forskolin (an adenylate cyclase activator) were similar in all experimental
      groups, suggesting that second-messenger mechanisms remain intact after
      normothermic cardiopulmonary bypass. In conclusion, basal cerebrovascular
      resistance and internal carotid artery blood flow are maintained if the systemic
      circulation and pressure are supported with fluid administration after
      cardiopulmonary bypass. Agonist-induced vasodilation of cerebral microvessels to
      cholinergic and beta-adrenoceptor stimulation are selectively impaired after
      normothermic cardiopulmonary bypass, whereas second-messenger mechanisms remain
      intact.

PMID- 8751516
TI  - Biocompatibility of heparin-coated extracorporeal bypass circuits: a randomized,
      masked clinical trial.
AB  - Cardiopulmonary bypass circuits cause morbidity during cardiac operations. Plasma
      proteins and cellular components are stimulated by contact with the
      cardiopulmonary bypass circuit and can cause bleeding and postperfusion syndrome.
      This is especially true in patients undergoing reoperative cardiac procedures,
      which carries a higher risk of postoperative bleeding and prolonged ventilation
      compared with primary cardiac surgical procedures. Recently, cardiopulmonary
      bypass circuit surfaces have been coated with antithrombotic agents to improve
      their biocompatibility. This study evaluated the effect of a heparin-coated
      cardiopulmonary bypass system (Duraflo II, Baxter Bentley Healthcare Systems,
      Irvine, Calif.) on thrombin formation, platelet stimulation, and leukocyte
      activation in patients undergoing reoperative coronary artery bypass grafting or
      valve operation. Fifty patients were selected and randomly assigned to a standard
      noncoated control system (n = 26) or the Duraflo heparin-coated system (n = 24).
      Similar heparin doses were used in both groups (3 mg/kg). The heparin-coated
      group used a completely heparin-coated bypass circuit including the cardiotomy
      reservoir; arterial filters were heparin-coated in both groups. Samples were
      obtained before cardiopulmonary bypass, 30 minutes into cardiopulmonary bypass, 5
      minutes after crossclamp removal, and 5 minutes after protamine administration.
      Thrombin formation (thrombin-antithrombin III by enzyme-linked immunosorbent
      assays) and platelet activation (beta-thromboglobulin by enzyme-linked
      immunosorbent assays; P-selectin expression by flow cytometry) were assayed.
      Leukocyte activation was determined by quantitative and qualitative analysis of
      arterial filters by scanning electron microscopy in six patients from each group.
      In both circuits, thrombin values increased markedly 30 minutes into
      cardiopulmonary bypass compared with baseline values (p < 0.001) (heparin-coated,
      7 +/- 5 to 96 +/- 115 ng/ml; noncoated, 10 +/- 9 to 115 +/- 125 ng/ml). Platelet
      activation as measured by beta-thromboglobulin (heparin-coated, 104 +/- 100 to
      284 +/- 166 IU/ml; noncoated, 81 +/- 74 to 288 +/- 277 IU/ml) and P-selectin
      expression (heparin-coated, 1.5% +/- 1.5% to 6.4% +/- 6.1%; noncoated, 1.4% +/-
      1.1% to 6.2% +/- 4.3%) also significantly increased 30 minutes into
      cardiopulmonary bypass compared with baseline values (p < 0.001). Platelet
      activation and thrombin generation did not differ between the two circuits at any
      time. Granulocyte activation and platelet deposition did not differ between the
      two circuits when arterial filters were evaluated. Both groups had similar
      heparin and protamine administration, blood transfusions, postoperative alveolar
      arterial oxygen gradient, time to extubation, length of intensive care unit stay,
      and overall morbidity and mortality. Clinical outcome and blood loss did not
      differ between the groups. We conclude that heparin-coated cardiopulmonary bypass
      circuits did not improve biochemical or clinical markers of biocompatibility in a
      reoperative patient population.

PMID- 8751517
TI  - Effects of failure of the right side of the heart and increased pulmonary
      resistance on mechanical circulatory support with use of the miniaturized HIA-VAD
      displacement pump system.
AB  - This experimental study was designed to assess the influence of failure of the
      right side of the heart or pulmonary hypertension, or both, on the performance of
      a novel miniaturized left ventricular assist device. In small-sized dogs (n = 50)
      ischemic global left ventricular failure was induced and support was provided by
      the HIA-VAD displacement pump (stroke volume 10 or 25 ml) installed as a left
      ventricular assist device. In three groups of animals (n = 10 each) pulmonary
      hypertension was created before induction of global left ventricular failure.
      During left ventricular assist device support temporary ischemic failure of the
      right side of the heart was induced in four groups of animals (n = 10 each). In
      the group subjected to left ventricular failure, support with the left
      ventricular assist device, and right ventricular failure during left ventricular
      assist, left atrial pressure and cardiac index were significantly lower than in
      the group subjected to left ventricular failure and left ventricular assist alone
      (2 +/- 6 versus 11 +/- 6 mm Hg and 1.6 +/- 0.4 versus 1.0 +/- 0.4 L/(min/m2),
      respectively, p < 0.05). In the group subjected to pulmonary hypertension, left
      ventricular failure, and left ventricular support, left atrial pressure dropped
      to values near zero but cardiac index remained unaltered as compared with results
      with the same regimen without pulmonary hypertension. However, when right
      ventricular failure was added (that is, pulmonary hypertension, left ventricular
      failure, left ventricular support, and right ventricular failure during support
      with the left ventricular assist device) left atrial pressure dropped to negative
      values (p < 0.05) and cardiac index progressively deteriorated. When, in an
      additional group of dogs, biventricular support was installed in the latter
      regimen, circulation was initially well supported but oxygenation deteriorated in
      60% of cases. We conclude that (1) adequate right ventricular function was
      indispensable during support with the left ventricular assist device, (2) the
      combination of pulmonary hypertension and right ventricular failure led to the
      "low left ventricular assist device output syndrome," and (3) biventricular
      mechanical support in the presence of pulmonary hypertension may be complicated
      by the alveolar leakage syndrome.

PMID- 8751518
TI  - Leukocyte depletion results in improved lung function and reduced inflammatory
      response after cardiac surgery.
AB  - Leukocyte depletion during cardiopulmonary bypass has been demonstrated in animal
      experiments to improve pulmonary function. Conflicting results have been
      reported, however, with clinical depletion by arterial line filter of leukocytes
      at the beginning of cardiopulmonary bypass. In this study, we examined whether
      leukocyte depletion from the residual heart-lung machine blood at the end of
      cardiopulmonary bypass would improve lung function and reduce the postoperative
      inflammatory response. Thirty patients undergoing elective heart operations were
      randomly allocated to a leukocyte-depletion group or a control group. In the
      leukocyte-depletion group (n = 20), all residual blood (1.2 to 2.1 L) was
      filtered by leukocyte-removal filters and reinfused after cardiopulmonary bypass,
      whereas in the control group an identical amount of residual blood after
      cardiopulmonary bypass was reinfused without filtration (n = 10). Leukocyte
      depletion removed more than 97% of leukocytes from the retransfused blood (p <
      0.01) and significantly reduced circulating leukocytes (p < 0.05) and
      granulocytes (p < 0.05) compared with the control group. Levels of the
      inflammatory mediator thromboxane B2 determined at the end of operation (p <
      0.05) were significantly lower in the depletion group than in the control group,
      whereas no statistical differences in interleukin-6 levels were found between the
      two groups. After operation, pulmonary gas exchange function (arterial oxygen
      tension at a fraction of inspired oxygen of 0.4) was significantly higher in the
      leukocyte-depletion group 1 hour after arrival to the intensive care unit (p <
      0.05) and after extubation (p < 0.05). There were no statistical differences
      between the two groups with respect to postoperative circulating platelet levels
      and blood loss, and no infections were observed during the whole period of
      hospitalization. These results suggest that leukocyte depletion of the residual
      heart-lung machine blood improves postoperative lung gas exchange function and is
      safe for patients who are expected to have a severe inflammatory response after
      heart operations.

PMID- 8751519
TI  - Applicability of intermittent global ischemia for repeat coronary artery
      operations.
AB  - Despite the increasing popularity of cardioplegic techniques there is no
      consensus as to the optimal myocardial protective technique for first-time or
      repeat coronary artery bypass grafting. Intermittent global ischemia was used in
      159 consecutive patients (142 male; 17 female) undergoing repeat coronary artery
      bypass grafting during a 6-year period (1987 to 1992). The median age of the
      patients was 60 years (90% confidence interval: 47 to 70 years) and the median
      interval from the first operation was 9 years (90% confidence interval: 2 to 14
      years). One third of the patients required emergency (within 24 hours) or urgent
      (within 7 days) operations because of failure of symptoms to resolve with medical
      therapy. Compared with events at the initial operation there was an increased
      prevalence of impaired ventricular function (ejection fraction < 50%) and
      increased use of the internal thoracic artery (48% versus 9%). Two of 12 patients
      who required emergency operations died in the hospital, which resulted in an
      overall mortality rate at 30 days of 1%. Intraaortic balloon pump support was
      required in five patients (3%) and cardiac dose inotropic support in 21% of
      patients for up to 24 hours after operation. There was definite
      electrocardiographic evidence of infarction in 11 patients (7%). The mean
      postoperative blood loss, without aprotinin, was 627 ml (standard deviation 327
      ml) and two patients required reexploration because of bleeding. Five patients
      had a hemiparesis (3%) and a further four patients (3%) had a mild or transient
      postoperative focal neurologic deficit. The median postoperative hospital stay
      was 9 days (90% confidence interval: 7 to 20 days) although 10% of patients
      required a hospital stay in excess of 21 days. No patient was lost to follow-up.
      The median (and interquartile range) period of follow-up was 1.6 (1 to 3) years.
      Eight patients died in the follow-up period, which resulted in an estimated
      survival of 80% at 5 years. At a mean follow-up period of 2 years (and with or
      without antianginal medication) 83% of patients had no or minimal angina, 12% had
      angina on moderate exertion, and 5% had angina on minimal exertion. In comparison
      with other current series of repeat coronary revascularization our results
      suggest that repeat coronary artery bypass grafting can be done with intermittent
      global ischemia with early and intermediate results at least equivalent to those
      obtained with cardioplegic methods.

PMID- 8751520
TI  - Effects of myocardial ischemia on the release of cardiac troponin I in isolated
      rat hearts.
AB  - BACKGROUND: The twofold aim of this experimental study was (1) to verify the
      correlation between the duration of ischemia and concentration of cardiac
      troponin I and (2) to compare the release of cardiac troponin I with histologic
      findings. METHODS: Experiments were done on 18 rat hearts, which were perfused
      according to the Langendorff method, immediately after excision in group I
      (control group) and after immersion for 3 hours (group II) and 6 hours (group
      III) in St. Thomas' Hospital solution at 4 degrees C. During reperfusion, the
      release of cardiac troponin I, creatine kinase isoenzyme MB, and lactate
      dehydrogenase, the recovery of left ventricular pressure, and heart rates were
      compared among the three groups. After the experiment, three samples of
      myocardium (left ventricle, right ventricle, and septum) were taken for
      histologic examination. RESULTS: Cardiac troponin I concentration was
      significantly higher in group III than in groups I and II and in group II
      compared with group I. Cardiac troponin I concentration increased as the ischemic
      period increased. The relation between cardiac troponin I release and ischemic
      duration tended to be linear. Creatine kinase MB and lactate dehydrogenase
      concentrations did not differ from one group to the other. Left ventricular
      pressure was not significantly different among the groups. In the control group,
      no heart had more than 10% of the myocytes affected. One of six hearts in group
      II and three of six in group III had more than 10% of myocytes affected.
      CONCLUSION: This experimental study showed (1) that cardiac troponin I is an
      early marker of ischemic injury and (2) that cardiac troponin I concentration
      increases as the ischemic period increases. Early cardiac troponin I release
      appears to correlate with the extent of ischemic injury in rats undergoing buffer
      perfusion.

PMID- 8751521
TI  - The effect of temperature management during cardiopulmonary bypass on neurologic
      and neuropsychologic outcomes in patients undergoing coronary revascularization.
AB  - Several studies suggest that normothermic ("warm") bypass techniques may improve
      myocardial outcomes for patients undergoing cardiac operations. Normothermic
      temperatures during cardiopulmonary bypass may, however, decrease the brain's
      tolerance to the ischemic insults that accompany all cardiac procedures. To
      assess the effect of bypass temperature management strategy on central nervous
      system outcomes in patients undergoing coronary revascularization, 138 patients
      were randomly assigned to two treatment groups: (1) hypothermia (n = 70),
      patients cooled to a temperature less than 28 degrees C during cardiopulmonary
      bypass, or (2) normothermia (n = 68), patients actively warmed to a temperature
      of at least 35 degrees C. Patients underwent detailed neurologic examination
      before the operation, on postoperative days 1 to 3 and 7 to 10, and at
      approximately 1 month after operation. In addition, a battery of five
      neuropsychologic tests was administered before operation, on postoperative days 7
      to 10, and at the 4- to 6-week follow-up visit. Patients in the normothermic
      treatment group were older (65 +/- 10 vs 61 +/- 11 years in the hypothermic
      group), had statistically less likelihood of preexisting cerebrovascular disease,
      and had higher bypass blood glucose values (276 +/- 100 mg/% vs. 152 +/- 66 mg/%
      in the hypothermic group). All other patient characteristics and intraoperative
      variables were similar in the two treatment groups. Seven of 68 patients in the
      normothermic group were found to have a central neurologic deficit, compared with
      none of the patients cooled to 28 degrees C (p = 0.006). Performance on at least
      one neuropsychologic test deteriorated in the immediate postoperative period in
      more than one half of all patients in both treatment groups but returned to
      preoperative levels approximately 1 month after the operation in most (85%). This
      pattern was not related to bypass temperature management strategy. We conclude
      that active warming during cardiopulmonary bypass to maintain systemic
      temperatures > or = 35 degrees C increases the risk of perioperative neurologic
      deficit in patients undergoing elective coronary revascularization.

PMID- 8751523
TI  - Is the heart a source for elevated circulating endothelin levels during aorta
      coronary artery bypass grafting surgery in human beings?
AB  - Reports have shown increased systemic levels of endothelins during coronary
      artery bypass grafting in human beings. It was not known whether increased
      endothelin levels during coronary artery bypass grafting reflect a general
      systemic response to the surgical procedure or increased myocardial production of
      endothelins in response to ischemia and reperfusion. We therefore measured
      endothelin levels in the right atrium and proximal aorta of 15 patients
      undergoing coronary artery bypass grafting for anginal syndrome immediately
      before aortic crossclamping and again after cessation of cardiopulmonary bypass.
      In five patients, we also measured coronary sinus levels of endothelins during
      cardiopulmonary bypass circulation. We found that endothelin levels were elevated
      throughout the surgical procedure. Right atrial endothelin levels were
      significantly elevated after cessation of cardiopulmonary bypass circulation with
      respect to values immediately before aortic crossclamping (11.1 +/- 3.1 vs 14.2
      +/- 3.7 pg/ml, p = 0.008), whereas endothelin levels in the proximal aorta did
      not rise significantly (10.5 +/- 2.3 vs 11.6 +/- 2.4 pg/ml, p > 0.5). Coronary
      sinus endothelin levels tended to decline temporarily during cardiopulmonary
      bypass circulation (11.1 +/- 2.1 pg/ml before aortic crossclamping, 7.9 +/- 1.9 1
      minute after release of aortic crossclamp, and 9.9 +/- 2.1 pg/ml after release of
      partial aortic crossclamping, p = 0.06). We conclude that the rise in right
      atrial endothelin levels during coronary artery bypass grafting reflects systemic
      production and secretion of endothelins, probably by vasculature or organs distal
      to the proximal aorta, and is not the result of increased myocardial production
      and secretion of endothelins.

PMID- 8751522
TI  - Low-dose and high-dose aprotinin improve hemostasis in coronary operations.
AB  - Prophylactic aprotinin therapy has become a popular method to reduce bleeding
      associated with cardiac operations. Today essentially two dose regimens are used,
      a high-dose regimen with administration throughout the complete operative
      procedure and a low-dose regimen with administration only during bypass. In
      unblinded studies both regimens were found to be equally effective. This double
      blind placebo-controlled study in 115 patients undergoing elective coronary
      artery bypass grafting was done to confirm these results without potential
      investigator bias. Intraoperative hemoglobin loss was significantly reduced (p <
      0.01) by 42% in the high-dose group and by 17% in the low-dose group compared
      with loss in control subjects. Blood loss 6 hours after operation was 377 ml in
      the low-dose and 266 ml in the high-dose group compared with 630 ml in the
      placebo group (p < 0.05 and p < 0.001, respectively). The average number of
      transfusions with packed red blood cells was reduced 31% in the low-dose group
      and 45% in the high-dose group, but the reductions were not significant. In a
      subgroup of patients, markers for coagulation and fibrinolysis were studied to
      investigate whether a different extent of activation existed. Fibrinolysis as
      measured by D-dimer levels was completely inhibited by the high-dose regimen, but
      was only partly suppressed in the low-dose group as compared with findings in the
      placebo group. Thrombin generation during cardiopulmonary bypass as reflected by
      F1 + 2 levels was lower in patients treated with aprotinin, but the difference
      was not significant. Concentrations of thrombin inactivated by antithrombin III
      were not different between the groups. The observation that low-dose aprotinin
      significantly improved hemostasis but did not inhibit hyperfibrinolysis supports
      our previous finding that low-dose aprotinin mainly protects platelet adhesive
      function. The better result obtained with high-dose aprotinin may indicate the
      contribution of hyperfibrinolysis to bleeding after cardiopulmonary bypass.
      Because high-dose aprotinin is administered outside the period of full
      heparinization and might therefore increase the risk of thromboembolic
      complications, we propose a modification of the low-dose schedule to increase
      aprotinin levels sufficient for plasmin inhibition before release of the aortic
      crossclamp.

PMID- 8751524
TI  - Aprotinin and aortic cannula thrombosis.

PMID- 8751525
TI  - Recurrent thrombosis of biventricular-support devices associated with accelerated
      intravascular coagulation and increased heparin requirements.

PMID- 8751526
TI  - Does inhaled nitric oxide suppress endogenous nitric oxide production?

PMID- 8751527
TI  - Evans blue and gentian violet: alternatives to methylene blue as a surgical
      marker dye.

PMID- 8751528
TI  - Erosion of inlet cannula of left ventricular assist device manifested as
      innocuous bleeding in stable patient: lessons learned in prevention of
      catastrophic consequences.

PMID- 8751529
TI  - Descending branch of lateral femoral circumflex artery as a free graft for
      myocardial revascularization: a case report.

PMID- 8751530
TI  - Cytomegalovirus pneumonia after cardiovascular operations.

PMID- 8751531
TI  - Myocardial infarction after a maze procedure for idiopathic atrial fibrillation.

PMID- 8751532
TI  - Tricuspid papillary fibroelastoma causing syncopal episodes.

PMID- 8751533
TI  - Multiple small fenestrations created during construction of the total
      cavopulmonary circulation: subsequent course and spontaneous closure.

PMID- 8751534
TI  - Late follow-up of tricuspid valve replacement for unguarded tricuspid anulus.

PMID- 8751535
TI  - The benefit of heparin-bound circuits.

PMID- 8751536
TI  - Transcervical approach (Dartevelle technique) for resection of lung tumors
      invading the thoracic inlet, sparing the clavicle.

PMID- 8751537
TI  - Human cytokine responses to cardiac operations: prebypass factors.

PMID- 8751538
TI  - Samuel Robinson (1875-1947).

PMID- 8751539
TI  - Stage IB1 vs IB2 carcinoma of the cervix: should the new FIGO staging system
      define therapy?

PMID- 8751540
TI  - Radical hysterectomy--the treatment of choice for early-stage cervical carcinoma.

PMID- 8751541
TI  - Radical hysterectomy for stage IB1 vs IB2 carcinoma of the cervix: does the new
      staging system predict morbidity and survival?
AB  - Two hundred twenty-nine patients with Stage IB cervical cancer treated with
      radical hysterectomy were assigned to the new FIGO substages IB1 (n = 181) and
      IB2 (n = 48) based on clinical tumor diameter. Our purpose was to determine the
      impact of the new staging system for IB1 and IB2 cervical cancer on nodal status
      and survival. Additionally, we analyzed the morbidity of radical hysterectomy in
      light of the new staging system. The complications were similar between the two
      groups. Para-aortic lymphadenectomy was the only independent predictor of
      complications (P = 0.00026). Stage IB2 patients did have a significantly worse 5
      year survival (72.8%) when compared with IB1 (90.0%) (P = 0.0265). Multivariate
      stepwise logistical regression analysis indicated that the new staging system did
      not have an independent impact on survival. Stage acts through nodal status in
      its impact on survival. Positive lymph nodes, tumor diameter, and Ponderal Index
      are all independent predictors of survival (P = 0.0001). Patients with Stage IB2
      carcinoma of the cervix undergoing radical hysterectomy showed no significant
      increase in morbidity when compared with patients with Stage IB1 disease treated
      with the same procedure.

PMID- 8751542
TI  - Academic medicine: as threatened as most would have us believe?
AB  - All academic health centers (AHCs) are threatened by the complexity of health
      care reform and by the speed with which it is occurring. We have been forced in
      all areas of our academic and clinical life to reassess the way in which we have
      traditionally operated. We must, in fact, do more than reassess. We must change
      fundamentally. This is true whether one considers medical education, biomedical
      research, or clinical services. Practically speaking, health care reform forced
      on us by the business community of America realistically means downsizing unless
      faculties are willing to change and pursue novel contemporary opportunities. It
      means less money and the need to do more with what we have. Educationally, we
      must emphasize the training of generalist physicians. On the research side, it
      means interdepartmental collaboration around core program project initiatives. It
      means a sharing of resources (including space) and the need to develop quality
      relationships with industry and philanthropic organizations. On the clinical
      side, we must develop a fully integrated, highly competitive, cost-efficient
      physician/hospital organization, and most AHCs must become part of a larger
      integrated delivery system to protect not only clinical but academic interests.

PMID- 8751543
TI  - Expression and function of autocrine motility factor receptor in human
      choriocarcinoma.
AB  - OBJECTIVE: Our purpose was to determine whether human choriocarcinoma cells
      express autocrine motility factor receptor (AMF-R) and to study its function in
      this tumor system. STUDY DESIGN: The expression and localization of AMF-R were
      compared in choriocarcinoma and normal placental trophoblasts using both cell
      lines and tissue sections. In addition, migratory properties of choriocarcinoma
      cells and normal placental cells was determined. RESULTS: Using
      immunofluorescence and immunoperoxidase staining, we have detected the expression
      of AMF-R in choriocarcinoma cells with receptor clustering on the cell surface,
      while term placenta cells expressed AMF-R less intensely with no receptor
      clustering. In choriocarcinoma tissues, AMF-R was strongly expressed in malignant
      cytotrophoblasts cells while adjacent normal villous trophoblast cells and
      necrotic regions were weakly or negatively stained. Choriocarcinoma cells
      responded to AMF-R stimulation with increased cell motility, while term placental
      cells were unresponsive. CONCLUSION: Human choriocarcinoma cells express
      functional cell surface AMF-R in vitro and in choriocarcinoma tissue suggesting
      that this receptor may play an important role in cancer cell motility.

PMID- 8751544
TI  - Paclitaxel delivered as a 3-hr infusion with cisplatin in patients with
      gynecologic cancers: unexpected incidence of neurotoxicity.
AB  - In an effort to develop a paclitaxel plus cisplatin combination chemotherapy
      regimen which can be easily employed in the outpatient setting, 38 patients
      (median age, 59; range, 39-72) with gynecological malignancies (20 ovarian; 6
      primary peritoneal; 12 endometrial) seen at the Cleveland Clinic Foundation from
      June 1993 to May 1995 were administered 170 cycles of paclitaxel (135 or 175
      mg/m2) over 3 hr followed by cisplatin (starting dose 75 mg/ m2). Of the 33
      patients with elevated CA-125 levels prior to the initiation of chemotherapy, all
      experienced > 50% decreases in this antigen level, while 23/33 (70%) had > 90%
      reductions. In general, nonneurologic side effects were mild in severity and
      easily manageable. Unfortunately, 71% of the patients developed neurologic
      toxicity, with one-fifth of the treated population experiencing severe neurotoxic
      side effects (grade 3-4). We conclude that paclitaxel administered over 3 hr at a
      dose of 135 or 175 mg/m2, followed by cisplatin (75 mg/m2), is a highly active
      regimen in gynecologic malignancies. Unfortunately, in our experience, the
      incidence and severity of neurotoxicity with this regimen is considerably greater
      than that reported with paclitaxel administered over 24 hr in combination with
      cisplatin. As a result of the observed toxicity profile, this drug delivery
      schedule for cisplatin and paclitaxel cannot be recommended for general clinical
      use.

PMID- 8751545
TI  - Intraabdominal lymphatic mapping to direct selective pelvic and paraaortic
      lymphadenectomy in women with high-risk endometrial cancer: results of a pilot
      study.
AB  - OBJECTIVE: To determine the feasibility of intraperitoneal lymphatic mapping of
      the uterine fundus as a means of identifying target sites for lymph node biopsy
      during staging laparotomy and to develop preliminary experience with the
      technique. METHODS: Fifteen women with high-risk endometrial tumors were entered
      on this Institutional Review Board-approved pilot study. At laparotomy, isosulfan
      blue dye (1.0 ml) was injected into the subserosal myometrium at three sites: the
      superior midpoint of the fundus, 2 cm inferiorly on the anterior wall, and 2 cm
      inferiorly on the posterior wall. Dye uptake into lymphatic channels was observed
      for 10 min. The retroperitoneal spaces were opened. Blue lymphatic channels and
      nodes within the pelvic and paraaortic regions were identified. Nodes
      demonstrating dye uptake were biopsied as separate specimens: the locations of
      these nodes were carefully recorded. Hysterectomy and selective lymphadenectomy
      were then performed as usual. RESULTS: Lymphatic channels coursing into the broad
      ligament and along the ovarian vessels were identified from all uteri injected.
      Deposition of dye into grossly identifiable lymph nodes was seen in 10 of 15
      cases (67%). A total of 31 nodes demonstrated dye uptake. The locations of these
      nodes included paraaortic sites in 12, common iliac in 6, and pelvic in 13. No
      dye-containing paraaortic nodes were seen below the origin of the inferior
      mesenteric artery. Lymphatic channels coursing above the renal vessels were seen
      routinely. Microscopic nodal metastases to sentinel nodes were identified in 2 of
      4 women with proven lymphatic spread. CONCLUSIONS: Lymphatic mapping of the
      uterine fundus is feasible and can identify targets for selective nodal biopsy in
      some women. Preliminary observations confirm that the lymphatic network draining
      the uterus is complex and involves both pelvic and paraaortic nodes. Lymphatic
      channels that parallel the ovarian vessels were not observed to enter nodes until
      reaching the level of the midabdomen. Further experience and refinement of
      techniques may lead to the development of a selective lymphadenectomy based upon
      direct visualization of the lymphatic drainage of the uterus rather than the
      current random sampling.

PMID- 8751546
TI  - Markov texture parameters as prognostic indicators in endometrial cancer.
AB  - BACKGROUND: Texture is a descriptive property of a surface distinct from color
      and shape. Image analysis allows gray-scale images to have their optical texture
      measured and analyzed. The authors, utilizing image analysis, prospectively
      studied Markov texture parameters to determine their relevance as prognostic
      indicators of disease recurrence in endometrial cancer. METHODS: Seventy-four
      consecutive patients, surgically treated, with endometrial cancer, were evaluated
      for their DNA index (DI), time to recurrence, peritoneal cytology, depth of
      invasion, lymphovascular space invasion, FIGO stage, grade, histology, as well as
      21 Markov parameters. DI and the Markov parameters were quantified using image
      analysis. RESULTS: Median follow-up for the study population was 31 months with a
      range from 1 to 44 months. Fifteen patients had recurrence of their cancer and 12
      patients died from disease during the observation period of the study. Eleven
      Markov parameters showed significant correlation with increasing FIGO stage (P <
      0.05), while 14 Markov parameters showed significant correlation with survival (P
      < 0.05). Three Markov parameters, difference entropy (P = 0.025), information
      measure B (P = 0.01), and diagonal moment (P = 0.046), were demonstrated to be
      independent prognostic indicators along with the more traditional prognostic
      indicators, stage (P = 0.006), grade (P = 0.029), and depth of myometrial
      invasion (P = 0.03). CONCLUSION: Image analysis is able to quantify optical
      texture. Utilizing bivariate correlations and multivariate analysis, three of
      these parameters were demonstrated to be independent prognostic indicators in
      endometrial cancer, specifically difference entropy, information measure B, and
      diagonal moment.

PMID- 8751547
TI  - A phase I/II study of dose-intense paclitaxel with cisplatin and cyclophosphamide
      as initial therapy of poor-prognosis advanced-stage epithelial ovarian cancer.
AB  - Epithelial ovarian cancer patients with bulky residual tumor have a poor response
      to therapy and limited survival. We investigated the addition of dose-intense
      paclitaxel to cisplatin and cyclophosphamide for patients with FIGO III/IV
      epithelial ovarian cancer. Paclitaxel dose was intensified from 135 to 250 mg/m2
      and administered in combination with cisplatin at > or = 75 mg/m2 and
      cyclophosphamide at 750 mg/m2. Thirty-one of 36 patients (86%) and 25 (70%) had >
      or = 2 and > or = 3 cm residual disease after surgery, respectively. One-third
      had stage IV disease, and 80% had grade 3 tumors. The maximally tolerated doses
      (MTD) were paclitaxel at 250 mg/m2, cisplatin at 75 mg/m2, and cyclophosphamide
      at 750 mg/m2 on a 21-day cycle with G-CSF, 10 micrograms/kg/day. Administered
      dose intensity at the MTD was > or = 86%. Reversible grade 3 peripheral
      neuropathy occurred in 28% of patients and fever during neutropenia in 2/352
      cycles (0.5%). The pathologic response rate is 36% with an additional 25% having
      minimal microscopic disease. Median progression-free and overall survivals for
      patients receiving paclitaxel at 250 mg/m2 at a median potential follow-up of 22
      months have not been reached for the cohort nor for the > or = 3-cm subgroup.
      This regimen should be evaluated in a prospective, randomized clinical trial.

PMID- 8751548
TI  - Prognostic value of p53 and proliferating cell nuclear antigen expression in
      endometrial carcinoma.
AB  - The degree of expression of p53 and proliferating cell nuclear antigen (PCNA) was
      measured in archival samples from 221 patients managed surgically for endometrial
      carcinoma between 1979 and 1983. With use of primary antibodies to the p53
      protein (DO7) and PCNA (PC10), immunoperoxidase nuclear staining of paraffin
      embedded tissue was performed. The computerized CAS200 Image Analysis System was
      used to determine the percentage of nuclear area stained. There was no evidence
      to conclude that progression-free survival differed with respect to PCNA
      expression. In contrast, intense p53 expression (66% or more nuclear area
      stained) was significantly associated with compromised progression-free survival
      both in the analysis of all stages (P < 0.001) and in the subset of patients with
      stage I disease (P < 0.001). Intense expression of p53 was significantly
      associated with other prognostic indicators, including stage, grade, depth of
      myometrial invasion, histologic subtype, cytologic findings, DNA ploidy, and HER
      2/neu expression. Multivariate analysis identified four independent prognostic
      factors for progression-free survival in endometrial carcinoma: intense p53
      expression, histologic subtype, DNA ploidy status, and HER-2/neu expression. When
      none of these four independent factors are present, the 4-year progression-free
      survival is 96%. In contrast, it is 63% when one or more of these factors are
      present (P < 0.001) and 40% when two or more factors are present (P < 0.001).

PMID- 8751549
TI  - Fallopian tube cancer: incidence and role of lymphatic spread.
AB  - Lymphatic spread pattern in 17 cases of adenocarcinoma of fallopian tube is
      reported. Median age of the patients was 48 years. All patients underwent
      surgical staging including total abdominal hysterectomy, bilateral salpingo
      oopherectomy omentectomy, and appendectomy. Systematic pelvic and paraaortic
      lymphadenectomy was feasible in 15 cases. Majority of the patients (11 of 17
      cases, 64%) had advanced disease and showed serous adenocarcinoma (83%). Lymph
      nodes were involved in 10 of 17 cases (59%). Node metastases rate increased
      significantly (P < 0.01) with intraperitoneal stage of disease and with grading.
      Interestingly, positive nodes were also found in 2 cases (33%) of 6 patients with
      disease still limited to fallopian tube. Overall, patients with negative nodes
      had a median survival of 76 months, compared with only 33 months if node
      metastases were found. In conclusion, combined pelvic and para-aortic
      lymphadenectomy seems to be necessary for staging and perhaps for prognosis of
      this disease.

PMID- 8751550
TI  - Use of V-Y flap for vulvar reconstruction.
AB  - Less extensive surgical treatment has become possible for limited vulvar cancer.
      However, primary closure is advisable only when the defect is minimal and tissue
      replacement is always needed in radical excisions. Local flaps are always
      considered the first choice because of their characteristics of similarity to the
      resected area. The V-Y island flaps from the medial side of thigh constitute one
      of the numerous options. Clinical experience and anatomical studies demonstrate
      that this procedure is extremely safe thanks to the rich subcutaneous vascular
      network. After illustrating the theoretical bases and the indications of this
      surgical procedure, we report our experience. The V-Y technique is reliable,
      ensures good healing, and provides almost normal sensation. We conclude that, in
      most instances, it can be considered a good option for vulvar reconstruction for
      its versatility and rapidity of execution.

PMID- 8751551
TI  - DNA index by flow cytometric analysis: an additional prognostic factor in
      advanced ovarian carcinoma without residual disease after primary operation.
AB  - Patients with no macroscopic residual disease after primary cytoreductive
      operation are considered to have the most favorable prognosis among subjects with
      advanced ovarian carcinoma. Nevertheless, approximately half of these patients
      eventually die of recurrent disease. The identification of more cogent prognostic
      factors within this subcategory of patients might allow for improved design of
      postoperative adjuvant treatment. The prognostic significance of several clinical
      and pathologic factors, including DNA content, was evaluated in 27 patients
      afforded complete cytoreduction at primary operation who were participants in
      prospective clinical trials of adjuvant chemotherapy for advanced ovarian
      carcinoma. After a median follow-up of 120 months, 14 patients were alive without
      evidence of disease and 13 had died of progressive disease. DNA index provided
      statistically significant prognostic information on the outcome (P = 0.02).
      Eleven of the 16 patients with a DNA index more than 1.3 died of tumor (8-year
      survival, 35%), whereas only 2 of the 11 with a DNA index less than 1.3 died (8
      year survival, 79%). In addition, menopausal status was of borderline
      significance for predicting survival (P = 0.04). The prognostic impact of the DNA
      index became progressively more evident with longer follow-up. Confirmation of
      this observation in larger sample populations may provide useful information for
      designing future clinical trials for this prognostically favorable subset of
      patients who have optimal reduction with advanced ovarian epithelial carcinoma.

PMID- 8751552
TI  - p53 protein overexpression in early stage endometrial cancer.
AB  - Overexpression of p53 protein has been reported to correlate with a poor
      prognosis in endometrial cancer. Most endometrial adenocarcinomas are clinical
      stage I at the time of diagnosis and the majority of women to die of this
      neoplasm had stage I disease at initial presentation. The aim of our study was to
      evaluate the prognostic significance of p53 overexpression in early stage
      endometrial carcinoma. Ninety-two patients with surgically treated endometrial
      adenocarcinoma FIGO stage I were examined for overexpression of
      immunohistochemically detected mutant p53 protein. Follow-up time ranged from 0.4
      to 137.8 months (mean, 34.8). Thirteen women died of their tumor. A nuclear
      staining reaction for p53 was observed in eight cases. Women with p53 protein
      overexpression showed a significant poorer overall survival in univariate
      analysis (relative risk, 4.78; 95% confidence interval, 1.56-14.61; P = 0.006,
      Wald test) and also in multiple analysis adjusted for grading (relative risk,
      4.39; 95% confidence interval, 1.39-13.90; P = 0.01, Wald test). Histological
      grading and histologic stage did not correlate with p53 protein overexpression (P
      = 0.26, P = 1.0, respectively, exact chi 2 test). Immunohistochemically detected
      p53 protein overexpression in early stage endometrial adenocarcinoma could aid in
      predicting prognosis and subsequently have some impact on adjuvant therapy.

PMID- 8751553
TI  - Expression of CD44 and variant isoforms in cervical intraepithelial neoplasia.
AB  - The cell adhesion molecule CD44 and its variant isoforms have been found to be
      related to invasive and metastatic character of cancer cells. Their expression in
      gynecologic precancerous lesions has not yet been reported. Mouse monoclonal
      antibodies directed against a common epitope (CD44s) and exons 4v, 6v, and 9v
      were used to study the expression of CD44 and variant isoforms by
      immunohistochemistry in cervical intraepithelial neoplasia (CIN). Twenty tissue
      samples with normal cervical epithelium and 57 samples with CIN of different
      histological grades and different HPV status were included in this study. The
      standard CD44, CD44-4v, CD44-6v, and CD44-9v were expressed in normal cervical
      epithelium and in precancerous lesions. In distinct contrast to the normal
      epithelium, however, the standard CD44, CD44-4v, and 6v showed a reduced
      expression in precancerous lesions, whereas CD44-9v was significantly
      overexpressed. Expression of CD44 standard and CD44-4v was correlated with the
      histological grade but not with the HPV status. Compared with mild and moderate
      dysplasia, severe dysplasia and carcinoma in situ are associated with low
      expression of CD44s (P = 0.007) and of CD44-4v (P = 0.03). These observations
      reveal dynamic changes in CD44 expression during neoplastic cell transformation
      in cervical intraepithelial neoplasia.

PMID- 8751554
TI  - Ifosfamide and doxorubicin in the treatment of advanced leiomyosarcomas of the
      uterus: a Gynecologic Oncology Group study.
AB  - This is a Phase II groupwide study of the Gynecologic Oncology Group (GOG) to
      determine the toxicity and efficacy of a combination of ifosfamide and
      doxorubicin in patients with advanced or metastatic leiomyosarcomas of the uterus
      who had not received other chemotherapy. Thirty-five women were entered into this
      study; 1 patient was ineligible (primary not documented), leaving 34 patients
      treated with ifosfamide, 5.0 g/m2/24 hr, and mesna, 6.0 g/m2/36 hr, by continuous
      IV infusion preceded by doxorubicin, 50 mg/m2 iv over 15 min. Each course of
      therapy was repeated every 3 weeks if counts allowed. One patient was inevaluable
      for response, leaving 34 evaluable for toxicity and 33 evaluable for response of
      chemotherapy. GOG grade 3 or 4 granulocytopenia occurred in 17 patients (48.6%),
      2 patients developed granulocytopenic fever (5.7%), and 1 died of sepsis. Two
      patients developed grade 3 thrombocytopenia, and 1 died of cardiotoxicity. There
      were nine partial and one complete responses for an overall response rate of
      30.3%; the response duration averaged 4 months. The combination of ifosfamide and
      doxorubicin is toxic but has moderate activity in patients with advanced or
      metastatic leiomyosarcoma of the uterus.

PMID- 8751556
TI  - P53 expression in adenomyosis in endometrial carcinoma patients.
AB  - Histopathologic changes ranging from simple cystic hyperplasia to carcinoma in
      situ may be observed in adenomyotic foci in patients with endometrial carcinoma.
      These changes can be an area of concern and physicians should be aware of their
      clinicopathologic significance. We studied a total of 94 patients, including
      endometrial carcinoma with (28 patients) and without adenomyosis (56 patients),
      and control group of adenomyosis cases (10 patients) without endometrial
      carcinoma. The histopathological changes in adenomyosis in patients with
      endometrial carcinoma varied from endometrial glands resembling the basal
      endometrium (13 of 28) through simple hyperplasia (8 of 28) to complex atypical
      hyperplasia, resembling carcinoma in situ (7 of 28). Formalinfixed paraffin
      embedded tissues from 55 patients (45 endometrial carcinomas and 10 control
      adenomyosis) were stained with monoclonal antibodies against P53. P53 positivity
      was not detected in adenomyosis cases without endometrial carcinoma but was
      present in 7 of the endometrial carcinoma-related cases. P53 positivity was found
      in 14 of 45 endometrial carcinomas studied. In all of the adenomyosis-positive
      cases, the endometrium was also positive. In conclusion, adenomyosis with a range
      of hyperplastic to atypical changes is not uncommon in adenocarcinoma patients.
      Our findings regarding P53 positivity in adenomyosis are consistent with the
      hypothesis that hyperplastic and atypical changes in adenomyosis might be due to
      a carcinogenic field effect in the vicinity of endometrial carcinoma rather than
      by direct invasion.

PMID- 8751555
TI  - CUMC-6, a new diploid human cell line derived from a squamous carcinoma of the
      uterine cervix.
AB  - A new cell line, CUMC-6, has been derived from an invasive nonkeratinizing
      squamous cell carcinoma of the uterine cervix in a 31-year-old patient. It has
      been maintained in long-term culture for 61 months, and passaged over 300 times.
      Monolayer-cultured cells were polygonal in shape, showing a pavement-like
      arrangement and a tendency to pile up without contact inhibition. The epithelial
      nature of the cultured CUMC-6 cells was confirmed by transmission electron
      microscopy which demonstrated the presence of desmosomes and tonofilaments. The
      subcutaneous injection of cultured cells into nude mice gave rise to fast-growing
      tumors. The transplanted tumor showed similar histological features, but poor
      differentiation compared to the original tumor. Cultured CUMC-6 cells produced
      human chorionic gonadotropin beta-subunit (beta-HCG) and alpha-fetoprotein (AFP).
      Cytosol estrogen and progesterone receptors were not measured in this cell line.
      The results of isozyme analyses were distinct from the HeLa cell line. Repeated
      chromosome analysis from passage 6 to 300 revealed that most metaphases of this
      cell line contained diploid number of chromosomes. The structural abnormality
      consistently observed in this cell line was the elongation of short arm of
      chromosome 1. The G- or R-banded pattern of this chromosome suggested inv dup (1)
      (1pter-->1p34[symbol: see text] 1p21-->1p34[symbol: see text] 1p34-->1qter).
      Human leukocyte antigen (HLA) typing of CUMC-6 cells indicated the presence of
      DR12 and DQw3. Analysis of the DNA extracted from the CUMC-6 cells showed the
      presence of human papillomavirus (HPV) type 16 and 18 DNAs. The results of
      oncogene analyses using Southern blotting technique revealed amplification and
      rearrangement of oncogene c-myc and no amplification of oncogene L-myc. Using the
      polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)
      technique, we have screened CUMC-6 cells for p53 mutation in exons 4 to 9. No
      mobility shift was observed in this cell line. These results suggest that
      chromosome 1 abnormality, oncogene alteration, and HPV infection work together in
      cervical tumorigenesis.

PMID- 8751557
TI  - Retrospective review of gynecologic oncology patients with therapy-induced
      neutropenic fever.
AB  - We reviewed the course and outcome of gynecologic oncology patients with
      neutropenic fever (NF), and identified low-risk patients who might be candidates
      for outpatient management. Charts from patients with the discharge diagnosis of
      NF from 1990 to 1994 were reviewed for variables related to the febrile
      neutropenic episode. Outcome was evaluated in terms of the duration of
      neutropenia, length of hospital stay, NF treatment result, incidence of positive
      blood cultures, dose reduction in the subsequent course of chemotherapy, and
      death. Statistical associations between variables and outcome parameters were
      examined by the Student t test and chi 2 or Fisher's exact tests as indicated.
      Multivariate analysis by logistic regression was done to determine independent
      significance of variables. Forty-five episodes of NF were identified involving 40
      patients. The median duration of neutropenia following the diagnosis of NF was
      2.5 days. The source of fever was unexplained by exam or cultures in 25/45 (56%)
      episodes. There were two (4%) deaths. In 16/45 episodes, patients had been
      treated with at least one prior regimen of chemotherapy (median, eight courses).
      Episodes of NF in patients receiving second-line chemotherapy were associated
      with a prolonged time of neutropenia (> 3 days, P = 0.058); however, this did not
      translate into increased hospital stay, treatment failure, or death. Thirteen of
      45 (29%) NF episodes developed in patients while already hospitalized for medical
      or surgical conditions. In this group, cultures were positive in 64% of cases.
      The remaining 32 NF episodes developed in patients while at home. Patients who
      developed outpatient NF (ONF) had positive cultures in 23% of cases (P = 0.08)
      and had a median hospital stay of 4 days. No patient with ONF who remained
      hemodynamically stable during the first 12 hr of admission suffered serious
      morbidity. In a multivariate analysis, only bacteremia approached statistical
      significance in predicting a longer hospital stay (P = 0.07), and no variable
      studied was predictive of prolonged NF in the ONF group. Our retrospective
      analysis indicates that patients with ONF who remain stable during the initial 12
      hr of hospitalization might safely be discharged home with appropriate
      antibiotics. Prospective study of outpatient management of NF is required to
      confirm these findings.

PMID- 8751558
TI  - The prognostic significance of surgery, tumor size, malignancy grade, menopausal
      status, and DNA ploidy in endometrial stromal sarcoma.
AB  - To evaluate the prognostic significance of DNA ploidy in endometrial stromal
      sarcoma, the traditional clinical and histopathological prognostic variables and
      DNA ploidy in 48 patients with histologically verified endometrial stromal
      sarcoma were analyzed. Evaluable flow cytometric DNA histograms from paraffin
      embedded tissue from the tumor were obtained in 47 patients. In univariate
      analysis, malignancy grade (P < 0.001), cellular atypia (P < 0.001), tumor
      diameter (P = 0.001), and mitotic count (P = 0.002) were highly significant. Also
      menopausal status (P = 0.011), FIGO stage (P = 0.035), and free resection margins
      at primary surgery (P = 0.026) obtained significance, while vessel invasion and
      age did not. DNA ploidy was not significant. In Cox multivariate analysis, free
      resection margins at primary surgery were found to be the most important
      prognostic factor (P < 0.001), followed by malignancy grade (P = 0.002), tumor
      diameter (P = 0.019), and menopausal status (P = 0.019). DNA ploidy did not
      obtain significance. Free resection margins at primary surgery, malignancy grade,
      tumor diameter, and menopausal status are important prognostic factors in
      endometrial stromal sarcoma.

PMID- 8751559
TI  - Expression and localization of alpha v integrins and their ligand vitronectin in
      normal ovarian epithelium and in ovarian carcinoma.
AB  - In an extension of a previous in vitro study [Carreiras et al., Int. J. Cancer
      63, 530-536 (1995)] and in an effort to understand the adhesive interactions
      mediated by integrins within epithelial ovarian tumors, the presence of the alpha
      v and beta 3 subunits and that of vitronectin (Vn) in ovarian carcinomas at
      various stages of differentiation and in normal ovarian epithelium were
      comparatively investigated. The study was performed on material from 34 patients.
      By immunofluorescence, cryostat sections were analyzed for their expression of
      alpha v (34 cases), beta 3 (19 cases), and Vn (29 cases). alpha v was expressed
      in normal epithelium and in highly differentiated tumors as well as in a majority
      of moderately and poorly differentiated carcinomas with identical staining
      pattern. beta 3 subunit and Vn were also expressed in normal cases and highly
      differentiated carcinomas. However, they were lacking in most of the less
      differentiated tumors. The analysis of cases which were simultaneously tested for
      the presence of alpha v, beta 3, and Vn revealed that a large proportion of
      normal ovarian epithelium and highly differentiated tumors simultaneously
      expressed alpha v, beta 3, and Vn; in contrast, in all moderately and poorly
      differentiated carcinomas either beta 3 or Vn was absent. The potential role of
      the alpha v beta 3/Vn system in ovarian epithelium functions is discussed. It is
      also speculated that modifications of this system in ovarian carcinomas might
      contribute to tumor progression.

PMID- 8751560
TI  - Prognostic significance of c-erB-2 mRNA in ovarian carcinoma.
AB  - The oncogene specific mRNA of c-erbB-2 was detected by the S1 nuclease protection
      assay in 95 ovarian cancer specimens. In 79 primary carcinomas, we found 16 (20%)
      with strong expression, 13 (17%) with weak expression, 4 (5%) with very weak
      expression, and 46 (58%) with no expression. In 3 of 16 recurrencies (19%) a
      strong expression of c-erbB-2 mRNA was detected, in 2 (12%) weak expression was
      detected, and in 11 (69%) no expression of c-erbB-2 mRNA was detected. Kaplan
      Meier analysis revealed no significant association between strong expression of c
      erbB-2 mRNA and survival of the 79 patients with primary cancer. However, in the
      subgroup of patients with FIGO (International Federation of Gynecology and
      Obstetrics) stages III and IV (n = 60) a shorter median survival time (12 months)
      was obtained for patients with strong c-erbB-2 mRNA expression compared to
      patients with no, very weak, and weak c-erbB-2 mRNA expression (25 months, P =
      0.04). In addition, strong expression of c-erbB-2 mRNA did not depend on
      histologic grade, histologic type, and FIGO stage. Adverse prognostic factors
      include histologic type (serous carcinoma), high grade, high stage (FIGO stages
      III and IV), and residual of tumor after surgery. From our results we conclude
      that for all patients (FIGO stages I-IV) strong expression of c-erbB-2 mRNA is
      not a prognostic parameter, but in the subpopulation of patients with FIGO stage
      III and IV only, an association between strong c-erbB-2 mRNA expression and
      shorter median survival time was found, although statistical significance was
      weak (P = 0.04).

PMID- 8751561
TI  - A phase II trial of paclitaxel in patients with advanced or recurrent
      adenocarcinoma of the endometrium: a Gynecologic Oncology Group study.
AB  - OBJECTIVE: To determine the efficacy and toxicity of paclitaxel in advanced or
      recurrent adenocarcinoma of the endometrium. METHODS: Thirty patients with
      advanced or recurrent endometrial cancer with measurable disease not previously
      treated with chemotherapy were treated with paclitaxel, 250 mg/m2, over 24 hr
      with G-CSF, 5 mcg/kg/day, from Days 2 to 12. The cycle was repeated every 21
      days. Patients who had received previous pelvic radiation were treated at an
      initial paclitaxel dose of 200 mg/m2. Twenty-eight patients were evaluable for
      response, and 29 patients for toxicity. All patients were Gynecologic Oncology
      Group performance status 0,1, or 2. RESULTS: Complete responses were observed in
      4 (14.3%) and partial responses in 6 patients (21.4%) for a response rate of
      35.7%. Severe (grade 3 or 4) leukopenia or thrombocytopenia was seen in 18 and 2
      patients, respectively. Grade 3 or 4 gastrointestinal toxicity was seen in 5,
      neurotoxicity in 3, anemia in 2, and cardiac toxicity in 1 patients. Alopecia was
      reported in 16 patients. CONCLUSIONS: This dose and schedule of paclitaxel are
      active in patients with advanced or recurrent adenocarcinoma of the endometrium
      and should be considered for inclusion in phase III trials.

PMID- 8751562
TI  - Sensitization of human ovarian tumor cells by subtoxic CDDP to anti-fas antibody
      mediated cytotoxicity and apoptosis.
AB  - Treatment of drug-sensitive or resistant tumor cells with combination of anti-Fas
      antibody and drugs (e.g., CDDP) results in augmented cytotoxicity and synergy.
      This study examined a possible underlying mechanism of synergy achieved by anti
      Fas and CDDP. Three human ovarian tumor cell lines were selected for the studies,
      namely, the CDDP-sensitive A2780 and CDDP-resistant variants AD10 and C30 tumor
      cells. All three lines express Fas but are resistant to cytotoxicity by anti-Fas
      antibody. Treatment of tumor cells with monoclonal mouse antihuman Fas (IgM)
      antibody and CDDP resulted in significant augmentation of cytotoxicity and
      synergy in all three lines. The magnitude of synergy was a function of the
      concentrations of both the anti-Fas antibody and the CDDP used. Pretreatment of
      tumor cells first with CDDP, but not with anti-Fas and then treatment with anti
      Fas, resulted in synergy, suggesting that CDDP sensitizes the cells to anti-Fas
      mediated cytotoxicity. This was corroborated by inhibiting synergy by the
      addition of neutralizing anti-Fas (IgG) antibody. Sensitization of tumor cells by
      CDDP resulted in upregulation of surface Fas expression which was dependent on de
      novo protein synthesis. Findings similar to those obtained in cytotoxicity were
      also obtained in apoptosis as determined by DNA hypoploidy and DNA fragmentation.
      The effect of CDDP-mediated sensitization to anti-Fas and cytotoxicity was
      compared to CDDP-mediated toxicity. The addition of the antioxidant butylated
      hydroxyanisole (BHA) inhibited CDDP-mediated cytotoxicity in both AD10 and C30
      but not in A2780 ovarian tumor cells. However, BHA did not inhibit upregulation
      of Fas expression by CDDP in all three lines and further BHA did not inhibit the
      synergy achieved with combination of subtoxic concentrations of CDDP and anti-Fas
      (IgM) antibody. These findings revealed that CDDP exerts its cytotoxic effect and
      its sensitization to Fas cytotoxicity by different mechanisms. Since cytotoxic T
      lymphocytes (CTL) express Fas ligand and kill Fas+ target cells, a significant
      potentiation of tumor cell killing will be achieved following sensitization of
      tumor cells to Fas signaling by subtoxic concentrations of CDDP. These findings
      suggest a new approach for augmenting CTL-mediated immune interventions in the
      therapy of resistant ovarian tumor cells.

PMID- 8751563
TI  - Vulvar Merkel cell tumor with glandular and squamous differentiation.
AB  - A case of a Merkel cell tumor of the vulva is presented. In addition to the
      typical microscopic, immunohistochemical, and ultrastructural features of Merkel
      cell tumor, there were areas of squamous and glandular differentiation. This is
      the ninth reported case of a vulvar Merkel cell tumor, and the first where
      squamous and glandular differentiation were seen. The findings support an origin
      of Merkel cell tumors from pluripotential stem cells.

PMID- 8751564
TI  - Missed hysteroscopic detection of uterine carcinoma before endometrial resection:
      report of three cases.
AB  - Endometrial ablation or resection using hysteroscopy appears to be an effective
      treatment for menorrhagia resistant to medical therapy. Three patients with
      endometrial adenocarcinoma missed in the preoperative hysteroscopic and
      histological assessment and subjected to endometrial resection were collected in
      a multicenter study. One case was an early adenocarcinoma in the background of
      late proliferative endometrium in a 39-year-old woman. In the other two patients,
      ages 51 and 68, the adenocarcinoma developed in a polyp in a background of simple
      hyperplasia. Since hysteroscopy with endometrial biopsy might not be able to
      exclude the presence of an early intrauterine cancer, appropriate selection and
      accurate evaluation of patients are imperative before ablative surgery.
      Endometrial resection is preferred over endometrial laser ablation since it
      provides additional tissue for histologic examination.

PMID- 8751565
TI  - Lymphoproliferative disorder involving the cervix in a patient being treated with
      FK-506.
AB  - FK-506 is an immunosuppressive agent used mainly to prevent allograft rejection
      in organ transplant patients. Recently, it has been applied as a treatment for
      patients with autoimmune disorders. An entity called posttransplant
      lymphoproliferative disorder (PTLD) is a well-recognized result of
      immunosuppression in transplant patients receiving long-term immunosuppression.
      This disorder is a complication of treatment with FK-506 in 0.7 to 1.6% of
      transplant patients and is usually of B-cell origin. A majority of patients have
      serologic evidence of EBV infection. We report a case of a patient receiving long
      term FK-506 therapy for multiple sclerosis who developed lymphoproliferative
      disorder involving the cervix. We will discuss the possible role of FK-506
      initiation of this tumor.

PMID- 8751566
TI  - Adenocarcinoma of the cervix presenting as ovarian cancer: diagnostic
      considerations.
AB  - Patients with adenocarcinoma of the cervix usually present with either abnormal
      vaginal bleeding or abnormal papanicolaou smears. Rarely, they may present with
      an abdominopelvic mass. We report two patients with occult cervical
      adenocarcinoma who presented with an abdominopelvic mass and vaginal bleeding
      which simulated a primary ovarian cancer.

PMID- 8751567
TI  - Rapid growth of an ovarian clear cell carcinoma expressing LH/hCG receptor
      arising from endometriosis during early pregnancy.
AB  - The complete clinical course of a case of ovarian clear cell carcinoma expressing
      luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor arising from
      endometriosis in a pregnant woman is presented. A 31-year-old woman visited a
      private clinic in May 1993 for screening tests for infertility. Transvaginal
      ultrasonography revealed no abnormal findings in the uterus or ovaries. Her
      menstrual cycle was regular; however, a slight luteal insufficiency was noted.
      She had been treated with clomiphene, and soon became pregnant. She was diagnosed
      to be at 5 weeks gestation in June, and at the same time, an ovarian tumor with
      the diameter of 5 cm was identified. Since the tumor had grown rapidly and was 9
      cm in diameter 1 week later, she was referred to our hospital. When she was
      admitted to our hospital at 9 weeks gestation, the tumor diameter was 14 cm and
      we found the solid portion within the ovarian tumor. The levels of the tumor
      markers CA125 and CA19-9 were 106 and 51 U/ml, respectively. The crown-rump
      length of the fetus (24 mm) was compatible with the gestational age, and fetal
      heartbeat was confirmed. Under the diagnosis of ovarian carcinoma, right salpingo
      oophorectomy was performed at 10 weeks of gestation. Postoperative histological
      examination revealed a clear cell carcinoma and endometriosis of the right ovary.
      Immunohistochemically, the clear cell carcinoma stained positively for LH/hCG
      receptors and estrogen receptors, but not progesterone receptor. No malignant
      cells were detected by ascitic cytology. Exploratory specimens obtained at the
      time of operation from the left ovary and pelvic lymph nodes exhibited no
      malignant cells. Based on these findings, the pregnancy was allowed to proceed,
      and she delivered a 3010-g male baby at 39 weeks of gestation. She had no signs
      of recurrence for 2 years after the operation.

PMID- 8751568
TI  - Spontaneous rupture of the urinary bladder: a late complication of radiotherapy-
      case report and review of the literature.
AB  - The spontaneous intraperitoneal rupture of the urinary bladder is an extremely
      rare life-threatening event. There are often difficulties in establishing the
      diagnosis. A patient with spontaneous perforation of the urinary bladder, 15
      years after pelvic radiotherapy for carcinoma of the cervix is reported. Aspects
      of etiology, clinical presentation, diagnosis, and management are described.
      Special emphasis is placed on surgical management as it relates to long-term
      outcome.

PMID- 8751569
TI  - Endometriosis with myxoid change simulating mucinous adenocarcinoma and
      pseudomyxoma peritonei.
AB  - A case of endometriosis with myxoid change is presented here which raised concern
      for metastatic adenocarcinoma and pseudomyxoma peritonei. This is the second case
      similar to the one described previously in the literature. A 51-year-old woman
      underwent repair for an umbilical hernia. The tissue sections of the hernia
      specimen contained isolated pools of mucin surrounded focally by cuboidal-type
      epithelium. Subsequent CT scan of the abdomen and pelvis revealed a large right
      adenexal mass. These clinicopathologic findings raised strong suspicion for
      adenocarcinoma and pseudomyxoma peritonei. Intraoperative frozen section of the
      right ovary showed an endometriotic cyst. She underwent hysterectomy, bilateral
      salpingoophrectomy, partial omentectomy, and lysis of adhesions. Permanent
      sections revealed foci of endometriosis in both ovaries and cervix. Pools of
      acellular mucin were present in the omentum and bladder peritoneum. There was no
      evidence of malignancy in any of the specimen. The case illustrates that
      endometriosis with myxoid change can simulate with mucinous adenocarcinoma and
      pseudomyxoma peritonei.

PMID- 8751570
TI  - New surgical approach to invasive cervical cancer.

PMID- 8751571
TI  - Phase II trial with neoadjuvant chemotherapy.

PMID- 8751572
TI  - Incidence and effects on survival of abdominal wall metastases at trocar.

PMID- 8751573
TI  - A tale of two cities--one surgeon's perspective.

PMID- 8751574
TI  - Bombesin-mediated AP-1 activation in a human gastric cancer (SIIA).
AB  - BACKGROUND: Bombesin, a gut tetradecapeptide homologous to the mammalian gastrin
      releasing peptide (GRP), stimulates the growth of the human gastric cancer line
      SIIA through specific GRP receptors (GRP-Rs); the cellular mechanisms are not
      known. The purpose of our study was to (1) confirm functional GRP-R in SIIA and
      (2) determine whether bombesin alters the expression and binding activity of the
      AP-1 transcription factors, c-jun and jun-B. METHODS: SIIA cells were treated
      with bombesin, and intracellular calcium mobilization was measured by means of
      fura-2 spectrofluorometry. To assess changes in c-jun and jun-B, RNA and protein
      were extracted for Northern and Western blots, respectively; nuclear protein was
      extracted for gel mobility shifts to determine AP-1 binding activity. RESULTS:
      SIIA cells mobilized intracellular calcium in response to bombesin, exhibiting a
      functional cell-surface GRP-R. Bombesin treatment increased expression of both c
      jun and jun-B mRNA by 0.5 hours, with maximal expression at 1 hour; concomitant
      increases in steady-state levels of c-Jun and JunB protein were identified.
      Moreover, bombesin increased binding of the AP-1 proteins as shown by gel shifts.
      CONCLUSIONS: The SIIA human gastric cancer possesses functional GRP-R coupled to
      the calcium second messenger pathway. Further, bombesin stimulates expression of
      c-jun and jun-B mRNA and protein and increases binding activity of AP-1 proteins.
      Delineating the cellular pathways involved in bombesin-mediated gene activation
      will provide important insights into the mechanisms responsible for normal and
      neoplastic gut growth.

PMID- 8751575
TI  - Thyroid hormone and the gut: selective transcriptional activation of a villus
      enterocyte marker.
AB  - BACKGROUND: Thyroid hormone (T3) is an important regulator of gut mucosal growth,
      differentiation, and barrier function, but its mechanism of action in the
      gastrointestinal tract is largely unknown. The present studies were carried out
      to define the molecular mechanisms by which T3 alters gut gene expression.
      METHODS: In vivo: Adult, male, Sprague-Dawley rats were given three daily
      injections (intraperitoneal) of either saline solution or 30 micrograms/kg
      triiodothyronine. Small intestinal tissues were harvested, and Northern blot
      analyses were performed by using specific radiolabeled cDNA probes. In vitro: HT
      29 cells were transfected with reporter plasmids and treated with or without T3,
      and chloramphenicol acetyltransferase activity was measured. RESULTS: The T3
      induced changes in enterocyte gene expression occurred in villus enterocytes and
      not in crypt cells and were independent of food intake. Northern analyses with an
      intron-specific probe revealed that the T3 induction in intestinal alkaline
      phosphatase (IAP) expression occurs at the level of transcription. Transient
      transfection assays revealed no T3-induced changes under basal conditions but
      marked increases (sixfold, p < 0.001) when a T3-receptor (TR beta-1) plasmid was
      cotransfected. Furthermore, T3 was found to induce greater IAP reporter gene
      activity in differentiated (+ sodium butyrate) compared with undifferentiated HT
      29 cells. CONCLUSIONS: T3 induces IAP expression at the level of gene
      transcription. Both in vivo and in vitro, IAP transcriptional activation occurs
      to a greater extent in differentiated enterocytes than in undifferentiated crypt
      cells. Transactivation of the IAP gene by T3 is mediated via a DNA cis-element(s)
      located within the 2.4 kb segment present in the reporter gene.

PMID- 8751576
TI  - Cytokine-induced nitric oxide synthase gene transcription is blocked by the heat
      shock response in human liver cells.
AB  - BACKGROUND: Previously we demonstrated that the heat shock response (HSR)
      inhibits cytokine-stimulated nitric oxide (NO) synthesis and inducible NO
      synthase (NOS2) expression in hepatocytes. In this study we sought to determine
      the molecular basis of this inhibition using a human liver cell line. METHODS:
      After induction of the HSR by sodium arsenite or hyperthermia, the AKN-1 human
      liver cell line was treated with cytokines to stimulate NOS2 expression and NO
      production. Western blot analysis for hsp70 was performed, and NOS2 mRNA and 24
      hour NO synthesis were quantitated. Cytokine-induced NOS2 promoter activity of
      AKN-1 cells transfected with a 7.0 kilobase NOS2 promoter luciferase construct
      and NO production of AKN-1 cells transduced with the NOS2 gene were measured.
      RESULTS: Sodium arsenite or hyperthermia induced the synthesis of hsp70 protein
      in AKN-1 cells, indicating activation of the HSR. Cytokines stimulated high
      levels of NOS2 mRNA and NO production. However, prior induction of the HSR
      significantly inhibited NOS2 expression and NO synthesis. Cytokine-stimulated
      NOS2 promoter activity of transfected AKN-1 cells was decreased by 77%, but the
      HSR did not affect NOS2 enzyme activity in transduced AKN-1 cells. CONCLUSIONS:
      These findings indicate that the HSR inhibits cytokine-induced NOS2 expression
      and NO synthesis in AKN-1 cells by preventing NOS2 promoter activation. Effects
      on NOS2 protein translation or stability were not observed. These data suggest
      that the HSR, which is expressed in the liver after trauma, shock, or ischemia
      reperfusion, blocks NOS2 gene expression at the transcriptional level.

PMID- 8751577
TI  - Thiol-mediated redox regulation of neutrophil apoptosis.
AB  - BACKGROUND: Intracellular glutathione, an endogenous antioxidant, protects
      cellular function against oxidative stress. Because oxidative stress has been
      implicated in neutrophil apoptosis, we hypothesized that reduced thiol levels may
      induce apoptosis through an alteration in cellular redox state. METHODS: Human
      polymorphonuclear leukocytes (PMNs), were incubated with medium or with
      increasing concentrations of the reduced glutathione (GSH)-depleting agents
      diethylmaleate and diamide and buthionine sulfoximine, an inhibitor of GSH
      synthesis. Apoptosis was assessed by means of flow cytometry with propidium
      iodide DNA staining and confirmed morphologically. GSH was measured
      colorimetrically, and tyrosine phosphorylation was assessed by means of
      immunoblotting. RESULTS: Diethylmaleate and diamide induced a dose-dependent
      reduction in GSH and a corresponding increase in PMN apoptosis. This effect could
      be reversed with N-acetylcysteine, suggesting that diethylmaleate induces
      apoptosis through the depletion of GSH. The antioxidant pyrolidine
      dithiocarbamate had no effect. Because oxidants can mediate intracellular
      signaling via tyrosine phosphorylation, we therefore evaluated the effects of the
      tyrosine kinase inhibition on diethylmaleate-induced PMN apoptosis. Both
      genistein and herbimycin A reduced diethylmaleate-induced apoptosis and tyrosine
      phosphorylation. CONCLUSIONS: Sulfhydryl oxidation by diethylmaleate alone
      induces apoptosis, providing evidence of a redox-sensitive, thiol-mediated
      pathway of apoptosis. Furthermore, tyrosine phosphorylation appears to play an
      important role in this process. Because apoptosis is a critical mechanism
      regulating PMN survival in vivo, manipulation of PMN intracellular thiols may
      represents a novel therapeutic target for the regulation of cellular function.

PMID- 8751578
TI  - Protein expression of p53, bcl-2, and KI-67 (MIB-1) as prognostic biomarkers in
      patients with surgically treated, clinically localized prostate cancer.
AB  - BACKGROUND: Protein expression in the primary tumor of the tumor suppressor gene
      p53 and the proto-oncogene bcl-2 have been shown to be prognostic biomarkers of
      cancer recurrence after radical prostatectomy in patients with clinically
      localized prostate cancer. Cancer cell proliferation as measured by
      immunohistochemical markers such as the MIB-1 antibody for Ki-67 has recently
      been suggested to be of prognostic value in prostate cancer. The goal of this
      study was to determine the clinical use of p53, Ki-67 (MIB-1), and bcl-2
      immunohistochemical protein expression in the primary tumor as combined
      predictors of disease progression after radical prostatectomy (RP). METHODS:
      Protein expressions of p53, Ki-67, and bcl-2 were evaluated in archival paraffin
      embedded RP specimens from 162 patients monitored from 1 to 10 years (mean, 4.5
      years) and correlated to stage, grade, race, and serologic (prostate-specific
      antigen) recurrence after operation. RESULTS: Expression was detected in 112
      (69.1%), 44 (27.2%), and 62 (38.3%) of 162 patients for p53 (1+ or greater), bcl
      2 (1+ or greater), and Ki-67 (2+ or greater), respectively. Biomarker expressions
      were not correlated to age and race; however, all increased with increasing stage
      and grade. The degree of expression by percentage of malignant cells staining
      correlated to recurrence for p53 and Ki-67 but not for bcl-2. All three markers
      were correlated to raw and Kaplan-Meier recurrence by means of univariate
      analysis with recurrence estimates at 6 years of 60.7% versus 24.2%, 84.2% versus
      38.6%, and 72.4% versus 30.6% comparing positive versus negative expression of
      p53, bcl-2, and Ki-67, respectively. p53 and bcl-2 remained as independent
      prognostic markers by Cox multivariate regression analysis. Although Ki-67 did
      not remain an independent marker, it added prognostic use in certain subsets of
      patients. CONCLUSIONS: p53, bcl-2, and Ki-67 (MIB-1) appear to be important
      biomarkers to predict recurrence in patients with clinically localized prostate
      cancer after RP, and all three biomarkers deserve further study.

PMID- 8751579
TI  - Differentiation of medullary thyroid cancer by C-Raf-1 silences expression of the
      neural transcription factor human achaete-scute homolog-1.
AB  - BACKGROUND: Human achaete-scute homolog-1 (hASH1), a fetal neural transcription
      factor, is highly expressed in neuroendocrine tumors such as medullary thyroid
      cancer (MTC). Although hASH1 probably plays a part in the growth and development
      of these tumors, its precise role and mechanism are unknown. METHODS: To further
      elucidate the function and regulation of hASH1 in neuroendocrine tumor
      differentiation, we used a model of MTC tumor differentiation mediated by the
      ras/raf-1 signaling pathway. The MTC TT cells alone or transduced with a beta
      estradiol activatable raf-1 construct (TT: delta Raf-1:ER) were treated with beta
      estradiol or carrier. Northern analysis and nuclear run-off assays were performed
      to determine the hASH1 messenger RNA (mRNA) levels and transcription rate,
      respectively. RESULTS: The TT: delta Raf-1:ER cells treated with beta-estradiol
      underwent marked biochemical and morphologic changes, including cell rounding,
      increase in calcitonin transcription, loss of RET proto-oncogene expression, and
      cessation of cell growth. During this differentiation process expression of hASH1
      mRNA was silenced. Nuclear run-off experiments revealed that this decrease in
      steady-state hASH1 mRNA by raf-1 activation resulted predominantly from
      transcriptional inhibition. CONCLUSIONS: Silencing of hASH1 in parallel with loss
      of RET is associated with development of a mature C-cell differentiation pattern.
      Mechanisms leading to transcriptional silencing of hASH1 may be crucial in
      regulating the proliferative capacity or differentiation status of MTC.
      Downstream targets of hASH1 could play a role in C-cell proliferation and
      progression to MTC.

PMID- 8751580
TI  - Active immunotherapy of pancreatic cancer with tumor cells genetically engineered
      to secrete multiple cytokines.
AB  - BACKGROUND: Vaccination of tumor-bearing animals with tumor cells genetically
      engineered to secrete cytokines including interleukin-2 (IL-2) and interferon
      gamma (IFN-gamma) has been shown to induce effective tumor-specific immune
      responses capable of inhibiting local and metastatic disease. Previous
      unsuccessful attempts to enhance this immune response by means of the secretion
      of multiple cytokines possessing different immunologic mechanisms of action may
      have been due to the inherent inefficiency of the gene transfer systems used. We
      postulated that tumor cells genetically engineered by means of a novel gene
      transfer method resulting in high level secretion of both cytokines would be more
      effective than tumor cells secreting a single cytokine in inhibiting the growth
      of existing tumors. METHODS: Nonimmunogenic, murine pancreatic cancer cells
      (Panc02) were engineered to secrete IL-2, IFN-gamma, IL-2 and IFN-gamma, or
      neomycin phosphotransferase. Mice were inoculated with 5 x 10(5) parental Panc02
      tumor cells subcutaneously. Beginning 3 days later, animals then received a
      series of four weekly vaccinations with irradiated Panc02/Neo, Panc02/IL2,
      Panc02/IFN, or Panc02/IL-2/IFN. RESULTS: Treatment with Panc02/Neo, Panc02/IL-2,
      or Panc02/IFN resulted in 0%, 40%, and 30% tumor-free survival, respectively. In
      contrast, 80% of animals vaccinated with Panc02/IL2/IFN were free of tumor at 100
      days. All animals free of disease were resistant to subsequent tumor challenges.
      CONCLUSIONS: These data show that vaccination with tumor cells that secrete high
      levels of multiple cytokines was more effective in treating established
      pancreatic tumors and represents an improvement over existing single cytokine
      strategies.

PMID- 8751581
TI  - Angiogenesis induced by acidic fibroblast growth factor as an alternative method
      of revascularization for chronic myocardial ischemia.
AB  - BACKGROUND: The effect of periadventitial administration of acidic fibroblast
      growth factor (FGF) on coronary microvascular reactivity and blood flow was
      examined in the collateral-dependent and normally perfused myocardium. METHODS:
      Ameroid constrictors were placed on the proximal left circumflex (LCx) coronary
      artery in 14 pigs. In seven pigs acidic FGF (10 micrograms) was administered into
      the perivascular space of the proximal LCx artery by using an ethylene vinyl
      acetate copolymer slow release device. After 7 to 9 weeks coronary arterial
      microvessels (70 to 150 microns) were studied in a pressurized (40 mm Hg) no-flow
      state with video microscopy. RESULTS: Relaxation mediated by beta-adrenoceptors
      and induced by isoproterenol (p < 0.05), and endothelium-dependent relaxation
      induced by adenosine 5' diphosphate (ADP) (p < 0.05) of isolated microvessels
      from the collateral-dependent LCx region were markedly reduced compared with the
      respective responses of vessels from the normally perfused left anterior
      descending (LAD) artery region. Relaxation induced by the adenylate cyclase
      activator forskolin and the guanylate cyclase activator sodium nitroprusside were
      unaltered. Chronic treatment with acidic FGF normalized responses to
      isoproterenol (p < 0.001 versus nontreated LCx) and ADP (p < 0.001 versus
      nontreated LCx) in the collateral-dependent LCx region, whereas responses to
      forskolin and sodium nitroprusside were not changed. Blood flow in the collateral
      dependent LCx region (0.49 +/- 0.24 ml/min/gm) was less than that in the normally
      perfused LAD region (0.80 +/- 0.24 ml/min/gm, p < 0.05). Treatment with acidic
      FGF improved perfusion in the LCx region (0.80 +/- 0.06 ml/min/gm, p < 0.05) but
      did not significantly affect blood flow in the LAD territory (0.89 +/- 0.09
      ml/min/gm). CONCLUSIONS: The periadventitial delivery of acidic FGF normalizes
      vasomotor regulation by beta-adrenergic and endothelium-dependent mechanisms and
      improves myocardial perfusion to the collateral-dependent myocardium. This may
      have implications regarding the treatment of patients with severe coronary artery
      disease who are not ameneable to conventional methods of revascularization.

PMID- 8751582
TI  - Coenzyme Q10 protects coronary endothelial function from ischemia reperfusion
      injury via an antioxidant effect.
AB  - BACKGROUND: Cardiac ischemia reperfusion (I/R) injury causes coronary vascular
      dysfunction. Coenzyme Q10 (CoQ), which preserves cardiac mechanical function
      after I/R, recently has been recognized as a free radical scavenger. We
      hypothesized that CoQ protects coronary vascular reactivity after I/R via an
      antioxidant mechanism. METHODS: Rats were pretreated with either CoQ (20 mg/kg
      intramuscular and 10 mg/kg intraperitoneal [CoQ group]) or a vehicle (Control)
      before the experiment. Isolated perfused rat hearts were subjected to 25 minutes
      of global normothermic ischemia and 40 minutes of reperfusion. The reperfusion
      induced oxidative burst was directly assessed by lucigenin enhanced
      chemiluminescence. Coronary flow was measured at equilibration and after
      reperfusion with or without bradykinin, an endothelium-dependent vasodilator, and
      sodium nitroprusside (SNP), an endothelium-independent vasodilator. The effect of
      intracoronary infusion of hydrogen peroxide (H2O2 0.1 mumol/gm body weight given
      over 5 minutes), simulating the free radical burst after I/R, also was evaluated.
      RESULTS: I/R decreased the bradykinin-induced change in coronary flow (-5% +/- 4%
      versus 26% +/- 3% at equilibration; p < 0.05) and the SNP-induced change (+20% +/
      6% versus +56% +/- 5% at equilibration; p < 0.05). The coronary vasculature
      after H2O2 infusion revealed a similar loss in vasodilatory responsiveness (+4%
      +/- 4% in response to bradykinin, +35% +/- 8% in response to SNP; p < 0.05 versus
      equilibration). Pretreatment with CoQ improved BK-induced vasorelaxation after
      I/R (+12% +/- 2%; p < 0.05 versus control I/R) or H2O2 infusion (18% +/- 4%; p <
      0.05 versus control I/R) but failed to improve SNP-induced vasorelaxation. The
      CoQ pretreatment decreased the I/R-induced maximal free radical burst (9.3 +/-
      0.8 x 10(3) cpm versus 11.5 +/- 1.1 x 10(3) cpm; p < 0.05) during the early
      period of reperfusion. CONCLUSIONS: Endothelium-dependent vasorelaxation is more
      sensitive than endothelium-independent relaxation to I/R injury. Via a direct
      antioxidant effect, CoQ preserved endothelium-dependent vasorelaxation by
      improving tolerance to I/R injury.

PMID- 8751583
TI  - Perfluorocarbon supplementation and postischemic cardiac function.
AB  - BACKGROUND: During induced ischemia for cardiac surgery inefficient anaerobic
      energy mechanisms predominate. Sustaining aerobic metabolism with perfluorocarbon
      supplemented blood cardioplegia theoretically could lead to improved postischemic
      recovery. Therefore we studied functional recovery after myocardial ischemia,
      comparing perflubron (C8F17Br) supplemented blood cardioplegia to standard blood
      cardioplegia. METHODS: Nineteen dogs underwent 15 minutes of 37 degrees C global
      ischemia on cardiopulmonary bypass, followed by 90 minutes of cardioplegic arrest
      by use of blood cardioplegia with or without perflubron and then 30 minutes of 37
      degrees C reperfusion. During ischemia myocardial oxygen tension, temperature,
      and pH were measured. Postischemic left ventricular recovery was assessed by
      means of preload recruitable stroke work, exponential end-diastolic stress-strain
      regression, and preservation of adenosine triphosphate and energy charge.
      RESULTS: The addition of perflubron, a new shorter half-life, lecithin-emulsified
      perfluorocarbon, provided superior myocardial protection when compared with
      standard blood cardioplegia. This benefit was evidenced by significantly
      increased recovery of preload recruitable stroke work slope (71% +/- 8% versus
      42% +/- 9%), decreased myocardial edema, and enhanced end ischemic myocardial
      oxygen and pH levels. CONCLUSIONS: The reliable oxygen delivery system and
      endothelial-preserving properties of the perfluorocarbons may prove to be an
      invaluable asset in addition to standard blood cardioplegia in the preservation
      of postischemic ventricular function. These data support the further
      investigation of perfluorocarbon-enriched blood cardioplegia.

PMID- 8751584
TI  - Long-term survival of rat to mouse cardiac xenografts with prolonged blockade of
      CD28-B7 interaction combined with peritransplant T-cell depletion.
AB  - BACKGROUND: The hCTLA4Ig/mCTLA4Ig fusion protein of the extracellular domain of
      human/mouse CTLA4 and the Fc portion of the human/mouse immunoglobulin G1 block
      the CD28/B7 costimulatory T-cell activation pathway. We evaluated the effect of
      prolonged B7-CD28 blockade, T-cell depletion, or both on rat to mouse cardiac
      xenografts. METHODS: C57BL/6 (H-2b) mice receiving infant Wistar Furth (RT1u) rat
      cardiac xenografts were treated with anti-CD4 (GK1.5) and anti-CD8 (2.43)
      monoclonal antibodies (mAb; 0.2 mg intravenous each) on days -2 and 0, hCTLA4Ig
      or mCTLA4Ig every other day from day 0 until day 14 and then twice a week until
      day 50 or day 100, or both. Changes in cellular reactivity were assayed by mixed
      lymphocyte culture and cell-mediated cytotoxicity and the development of
      cytotoxic antibodies was serially measured after transplantation. RESULTS: Either
      human CTLA4Ig or murine CTLA4Ig alone led to significant prolongation of rat to
      mouse cardiac xenografts (median survival time [MST], 22 or 26 days, respectively
      [p = 0.008], versus control). hCTLA4Ig given for 50 days in combination with two
      doses of anti-CD4/CD8 monoclonal antibodies further prolonged graft survival
      (MST, 61 days; p versus control < 0.0001). In this combination, when hCTLA4Ig was
      continued until day 100, the graft survival was further prolonged (MST, 119
      days). mCTLA4Ig for 100 days plus anti-CD4/CD8 similarly prolonged rat xenograft
      survival (MST, 94 days). However, all cardiac xenografts eventually failed,
      primarily from humoral rejection. Cytotoxic antibody titers rose rapidly only in
      animals rejecting a graft, and suppressed cell-mediated immunity had completely
      recovered in rejecting recipients. CONCLUSIONS: Blockage of the CD28-B7
      costimulatory interaction can inhibit both humoral and cell-mediated immune
      responses and result in the prolonged acceptance of rat to mouse cardiac
      xenografts. Longer administration of CTLA4Ig and anti-CD4/CD8 monoclonal
      antibodies further prolongs but does not achieve indefinite survival of rat
      cardiac xenografts.

PMID- 8751585
TI  - Induction of specific tolerance through mixed hematopoietic chimerism prevents
      chronic renal allograft rejection in a rat model.
AB  - BACKGROUND: Chronic rejection is the leading cause of late graft loss in kidney
      transplantation. We tested the ability of mixed hematopoietic chimerism to
      prevent chronic renal allograft rejection in an established rat model and
      described possible mechanisms responsible for this tolerance. METHODS: Mixed
      hematopoietic chimerism was established in lethally irradiated F-344 rats by
      reconstitution with Lewis bone marrow. Four groups (n = 5 each) received
      orthotopic kidney transplants: (1) allograft controls, (2) isograft controls, (3)
      experimental chimeras, and (4) specificity control. After 120 days kidney grafts
      were examined histologically, immunohistochemically, and for cytokine interferon
      gamma, interleukin-2 (IL-2), IL-4, and IL-10 gene transcripts by means of reverse
      transcriptase polymerase chain reaction techniques. RESULTS: Allograft control
      group exhibited severe parenchymal fibrosis; isograft control and chimera groups
      failed to develop this lesion. Immunohistochemical analysis revealed increased
      CD8+ lymphocytes and ED-1+ monocyte-macrophages infiltrating the
      tubulointerstitium of control allografts. Interferon-gamma and IL-2 were absent
      in isografts. IL-4 was absent and IL-10 was positive in all grafts. Chimeras
      promptly rejected third-party allografts. CONCLUSIONS: Induction of specific
      tolerance through mixed hematopoietic chimerism prevents chronic renal allograft
      rejection. These results support the hypothesis of an immunologic basis of
      chronic rejection and advance previous observations that the induction of
      specific tolerance enables long-term solid organ transplantation without the use
      of immunosuppression.

PMID- 8751586
TI  - Insulin-like growth factor-I attenuates delayed graft function in a canine renal
      autotransplantation model.
AB  - BACKGROUND: Insulin-like growth factor-I (IGF-I) has been shown to accelerate
      recovery in animal models of ischemic or toxic acute renal injury. Ischemic renal
      injury is frequently encountered after cadaveric transplantation manifested as
      delayed graft function. This study was performed to determine whether perfusion
      of kidneys with preservation solution supplemented with IGF-I would improve the
      course of renal injury in a canine autotransplantation model of delayed graft
      function. METHODS: Dogs underwent unilateral nephrectomy with kidneys perfused
      and stored in Euro-Collins solution supplemented with vehicle (n = 11) or IGF-I
      (n = 8). After 24 hours of kidney preservation, a contralateral nephrectomy was
      performed and the stored kidney was autotransplanted. Renal function was examined
      for 5 days after the transplantation, and an inulin clearance was obtained at the
      time of death. RESULTS: Compared with dogs that received kidneys preserved in the
      vehicle, dogs receiving the IGF-I preserved kidneys had significantly lower daily
      serum creatinine and blood urea nitrogen levels during the course of 5 days after
      transplantation. Inulin clearance at death was nearly double in the IGF-I treated
      animals compared with the vehicle-treated controls (1.37 +/- 0.16 ml/min/kg
      versus 0.77 +/- 0.13 ml/min/kg; p < 0.05). CONCLUSIONS: Perfusion and storage of
      kidneys with preservation solution supplemented with IGF-I can attenuate the
      course of delayed graft function in a canine renal autotransplantation model. IGF
      I may have potential for use in cadaveric human renal transplantation.

PMID- 8751587
TI  - Intestinal intraepithelial lymphocytes influence the production of somatostatin.
AB  - BACKGROUND: We have previously demonstrated that intestinal intraepithelial
      lymphocytes (iIELs) inhibit lymphocyte proliferation. Because somatostatin also
      prevents lymphocyte proliferation, we hypothesized that iIELs may influence
      production of somatostatin. METHODS: Isolates of intestinal epithelium that were
      obtained from Brown Norway (BN) rats and contained an iIEL-enriched population
      (defined as CD45+) were incubated with irradiated Lewis splenocytes for
      allogeneic stimulation. BN rat splenocytes incubated with irradiated Lewis
      splenocytes served as a control. Supernatants were harvested after 4 days and
      assayed for somatostatin by using a radioimmunoassay. RESULTS: The somatostatin
      level in the intestinal epithelium-conditioned supernatant was significantly
      higher than that of the control group (176 +/- 60 versus 10 +/- 2 fmol/ml; p <
      0.05). Removal of the CD45+ cell subset resulted in a fifteenfold reduction in
      somatostatin levels. The CD45+ cell lysates had significantly higher levels of
      somatostatin than did CD45+ depleted cells (1304 +/- 531 versus 128 +/- 41
      fmol/ml; p < 0.05). CONCLUSIONS: The isolates of intestinal epithelium produced
      significant amounts of somatostatin. Removal of the CD45+ cells caused a
      significant loss of somatostatin production. Intracellular levels of somatostatin
      appeared to be highest in the CD45+ subpopulation. These data suggest that iIELs
      (that is, CD45+ cells) may have a significant influence on the production of
      somatostatin and may be a source of somatostatin production. Production of
      somatostatin by iIELs may help modulate immune responses in gut-associated
      lymphoid tissue.

PMID- 8751588
TI  - Expression of the somatostatin receptor subtype-2 gene predicts response of human
      pancreatic cancer to octreotide.
AB  - BACKGROUND: Somatostatin inhibits proliferation of many solid tumors. The current
      study examines whether inhibition of the growth of pancreatic cancer by the
      somatostatin analog, octreotide, requires tumor expression of somatostatin
      receptors. METHODS: We studied five human pancreatic cancer cell lines, Capan-1,
      Capan-2, CAV, MIA PaCa-2, and Panc-1. Solid tumors were established in nude mice
      (n = 20/cell line) by flank injection of tumor cells. Subcutaneous octreotide
      (500 micrograms/kg/day) was administered by osmotic pumps to 10 of the animals in
      each group, and the other 10 received control infusions of saline solution. On
      day 36, the tumors were excised and weighed. Plasma levels of the putative
      trophic peptides cholecystokinin, epidermal growth factor (EGF), insulin-like
      growth factor-1 (IGF-1), and insulin were assessed by radioimmunoassay. Each of
      the five cell lines was assayed for the presence of cell surface somatostatin
      receptors by using whole cell competitive binding assays with 125I-somatostatin.
      Expression of the somatostatin receptor subtype-2 (SSR2) gene was determined with
      reverse transcriptase-polymerase chain reactions. Southern blot hybridization was
      used to assess the presence of the SSR2 gene. RESULTS: Octreotide inhibited tumor
      growth in the MIA PaCa-2 group (512 +/- 75 mg control versus 285 +/- 71 mg
      treated; p < 0.05) but had no significant effect on tumor weight in the other
      four cell lines. Plasma levels of cholecystokinin, epidermal growth factor,
      insulin-like growth factor-1, and insulin were not altered by chronic octreotide
      infusion. Cell surface somatostatin receptors and SSR2 gene expression were
      detected only in the MIA PaCa-2 tumors. The gene for the SSR2 receptor was found
      in all five tumor lines. CONCLUSIONS: Octreotide-mediated inhibition of
      pancreatic cancer growth is dependent on expression of somatostatin receptors.
      The expression of somatostatin receptors should be considered in the design and
      interpretation of clinical trials with somatostatin analogs for treatment of
      pancreatic cancer.

PMID- 8751589
TI  - Pentagastrin selectively modulates levels of mRNAs encoding apical H/K adenosine
      triphosphatase and basolateral Na-K-Cl cotransporter in rat gastric fundic
      mucosa.
AB  - BACKGROUND: Gastrin regulates gastric acid secretion and gastric mucosal cell
      proliferation. We hypothesized that pentagastrin administration would affect mRNA
      levels of two membrane proteins that are important during stimulated states of
      HCl secretion, the basolateral Na-K-Cl cotransporter (BSC) and the apical H/K
      adenosine triphosphatase (H/K). METHODS: Two groups of Fischer rats received
      intraperitoneal injections of pentagastrin (2.5 or 25 micrograms/kg) every 8
      hours for three doses. A third group served as controls. An additional group
      received pentagastrin plus the gastrin receptor antagonist (GRA) L740,093. Fundic
      mucosae were subjected to semiquantitative Northern analysis of mRNAs encoding
      H/K and BSC. The mRNA for Na/K adenosine triphosphatase (Na/K), a transport
      protein not involved directly in acid secretion, also was evaluated. RESULTS:
      Administration of pentagastrin caused dose-dependent increases in levels of mRNAs
      encoding H/K and BSC but had no significant effect on levels of Na/K mRNA.
      Administration of GRA prevented the pentagastrin-induced changes in mRNA levels
      for these transporters. CONCLUSIONS: Pentagastrin administration selectively up
      regulates levels of mRNA encoding membrane proteins involved in acid secretion.
      The up-regulation of the mRNAs encoding BSC during pentagastrin stimulation
      indicates that regulation of basolateral Cl- movement may be as important as the
      regulation of apical H+ movement under stimulated states.

PMID- 8751590
TI  - Adenosine scavenging: a novel mechanism of chloride secretory control in
      intestinal epithelial cells.
AB  - BACKGROUND: Adenosine released by cells during ischemia typically serves as a
      feedback inhibitor of further organ work. However, in ischemic intestine,
      adenosine appears to act via stimulatory A2b receptors to increase work in the
      form of chloride ion (Cl-) secretion. This unusual response may contribute to
      luminal fluid sequestration in intestinal ischemia. In nonischemic cells feed
      forward activation of Cl- secretion does not occur despite the fact that
      adenosine may be continuously generated during normal cell metabolism. Thus we
      postulated that intestinal epithelia normally control the disposition of
      adenosine to prevent inappropriate activation of secretion. METHODS: Model T84
      intestinal epithelia were studied by means of electrophysiologic and isotopic
      techniques. RESULTS: Dipyridamole and nitrobenzylthioinosine (inhibitors of
      nucleoside transport) and iodotubercidin (an inhibitor of adenosine kinase)
      caused adenosine to accumulate extracellularly and induced a Cl- secretory
      response that was prevented by adenosine receptor blockade. Uptake of exogenous
      adenosine was restricted to the basolateral compartment and was blocked by
      nucleoside transport inhibitors. CONCLUSIONS: Adenosine released from nonischemic
      intestinal epithelial cells is scavenged by a basolaterally restricted adenosine
      transporter. This system maintains extracellular adenosine levels below the
      prosecretory threshold and thus limits adenosine-elicited activation of Cl-
      secretion (and hence diarrhea) under normal conditions).

PMID- 8751591
TI  - Tissue-specific regulation of glutamine synthetase gene expression in acute
      pancreatitis is confirmed by using interleukin-1 receptor knockout mice.
AB  - BACKGROUND: Acute pancreatitis causes a pronounced depletion of plasma and muscle
      glutamine pools. In several other catabolic disease states expression of the
      enzyme glutamine synthetase (GS) is induced in lung and muscle to support
      glutamine secretion by these organs. The hormonal mediators of GS induction have
      not been conclusively identified. We used mice deficient for the expression of
      the type 1 interleukin-1 receptor (IL-1R1 knockout mice) to investigate the
      expression of GS during acute edematous pancreatitis. METHODS: Acute edematous
      pancreatitis was induced in adult male wild-type and IL-1R1 knockout mice by
      means of the intraperitoneal administration of cerulein, and their conditions
      were monitored. Five organs, including lung, liver, gastrocnemius muscle, spleen,
      and pancreas, were assayed for relative GS messenger RNA (mRNA) content by
      Northern blotting. RESULTS: The ultimate severity of pancreatitis was reduced by
      IL-1R1 deficiency. GS mRNA levels increased during progression of pancreatitis in
      lung, spleen, and muscle tissue from each group. No consistent increase in GS
      mRNA level was observed in liver. IL-1R1 deficiency did not affect GS mRNA
      expression in lung tissue but consistently retarded GS induction in the spleens
      of knockout animals. IL-1R deficiency altered the kinetics of GS induction in
      muscle. CONCLUSIONS: Cerulein-induced experimental pancreatitis causes an
      induction in GS mRNA levels in a tissue-specific fashion. IL-1R1 deficiency
      reduced the ultimate severity of the condition and altered the induction of GS
      mRNA in the spleen and muscle.

PMID- 8751592
TI  - Active immunotherapy with transiently transfected cytokine-secreting tumor cells
      inhibits breast cancer metastases in tumor-bearing animals.
AB  - BACKGROUND: Metastatic disease remains the most frequent cause of treatment
      failure in the management of patients with breast cancer. A novel method that
      allows delivery of a gene into primary tumor cells was used to generate tumor
      cell vaccines to inhibit metastasis formation in tumor-bearing hosts. METHODS:
      Inoculation of 2.5 x 10(4) 4T1 murine breast cancer cells into the footpads of
      BALB/c mice reliably leads to tumor growth and pulmonary metastases. Interleukin
      2 (IL-2)-secreting 4T1 cells (4T1-pMP6A/IL-2) and control transduced 4T1 cells
      (4T1-pMP6A) were generated by lipofection with a cationic liposome complexed to
      an adeno-associated viral plasmid bearing the IL-2 gene (pMP6A/IL-2). Unmodified
      4T1 cells were inoculated into the footpads on day 0, and weekly immunization
      with phosphate-buffered saline solution or 2 x 10(6) irradiated 4T1, 4T1-pMP6A,
      or 4T1-pMP6A/IL-2 cells commenced on day 21. Hindlimb amputation was performed
      when tumors measured 6 mm in diameter. Mice were killed 24 days after amputation,
      and metastatic disease was determined by weighing lungs at time of harvest.
      RESULTS: A significant reduction was seen in the pulmonary metastatic load of
      mice receiving IL-2 gene-modified tumor cell immunization (4T1-pMP6A/IL2) when
      compared with mice given control immunizations. CONCLUSIONS: These results
      suggest that active immunization strategies with cytokine gene-modified tumor
      cells generated by clinically relevant gene delivery systems may prove useful in
      inhibiting the development of metastases from primary breast cancer.

PMID- 8751593
TI  - Cytokine production and antitumor effect of a nonreplicating, noncytopathic
      recombinant vaccinia virus expressing interleukin-12.
AB  - BACKGROUND: Cancer gene therapy with interleukin-12 (IL-12) has generated much
      interest because of the potent antitumor effects of this cytokine. The purpose of
      this study was to construct a nonreplicating, noncytopathic recombinant vaccinia
      virus (irecVV) encoding murine IL-12 (ivKT0327mIL-12) and to assess its biologic
      activity and antitumor effects. METHODS: ivKT0327mIL-12 was constructed by
      inserting the genes encoding mIL-12 into the VV genome by homologous
      recombination. Psoralen and long-wave ultraviolet light were used to render the
      virus incapable of replication or cell lysis. Cytokine production was assessed by
      infecting tumor cell lines and measuring mIL-12 in the culture supernatants by
      using a bioassay. C57BL/6 mice were injected subcutaneously in a randomized,
      blinded fashion with 5 x 10(5) MCA 101 fibrosarcoma cells or 5 x 10(5) PAN 02
      pancreatic tumor cells infected in vitro with either ivKT0327mIL-12 or ivKT033, a
      control irecVV containing no cytokine genes. Emergence of tumor and tumor size
      were measured. RESULTS: Tumor cells infected with ivKT0327mIL-12 produced large
      amounts of biologically active mIL-12 (up to 793 ng/10(6) cells/24 hr) but
      continued to proliferate in vitro with no cytopathic effect. Mice injected with
      MCA 101 infected with ivKT0327mIL-12 had significantly delayed tumor emergence (p
      < 0.03) and decreased tumor size (p < 0.003) compared with mice injected with
      ivKT033-infected MCA 101. Tumor growth was also significantly smaller in a
      similar experiment with PAN 02 (p < 0.01). CONCLUSIONS: Tumor cells infected with
      irecVV encoding mIL-12 express high levels of biologically active mIL-12 in vitro
      and exhibit delayed tumor establishment, significant tumor growth inhibition, or
      both, in vivo.

PMID- 8751594
TI  - Interleukin-10 prevents death in lethal necrotizing pancreatitis in mice.
AB  - BACKGROUND: Cytokines derived from macrophages may play an integral role in the
      evolution of acute pancreatitis. Interleukin-10 (IL-10), a potent
      antiinflammatory cytokine, prevents the activation of macrophages and their
      release of inflammatory cytokines. The aim of this study was to determine whether
      treatment with IL-10 decreased the severity of experimental acute pancreatitis.
      METHODS: Thirty female Swiss Webster mice were divided into three groups. Acute
      pancreatitis was induced by using a choline-deficient, 0.5% ethionine
      supplemented (CDE) diet. Group A (controls) received CDE diet alone. Group B was
      pretreated with 10,000 units of intraperitoneal IL-10 at the onset of feeding and
      every 8 hours thereafter. Group C received IL-10 33 hours after beginning the CDE
      diet and every 8 hours thereafter. One half of the animals in each group was
      killed at 54 hours; the remaining living animals were killed at 80 hours. Serum
      amylase levels (units per liter) were determined at 54 and 80 hours. Pancreata
      were harvested and fixed in formalin. Histologic characteristics were graded on a
      scale from 0 to 4 (normal to most abnormal) in a blinded fashion by two
      investigators. RESULTS: Serum amylase level and histologic score (edema,
      inflammation, hemorrhage, and necrosis) were significantly reduced when IL-10 was
      administered either prophylactically or therapeutically (p < 0.01). At 54 hours
      all animals were alive. Mortality was reduced at 80 hours in both groups treated
      with IL-10 compared with those fed the CDE diet alone (p < 0.001). CONCLUSIONS:
      These results suggested that macrophages play an integral role in determining the
      severity of acute pancreatitis in this animal model. The finding that IL-10
      decreased inflammation and prevented death, even when given after acute
      pancreatitis was established, suggests that it may have potential for clinical
      use.

PMID- 8751595
TI  - Interleukin-12 treatment restores normal resistance to bacterial challenge after
      burn injury.
AB  - BACKGROUND: Preliminary studies in this laboratory have shown that treatment with
      interleukin-12 (IL-12), a cytokine that induces expression of the T-helper-1
      lymphocyte phenotype, in an animal model of burn injury increased survival after
      a septic challenge. The purpose of this study was to define the efficacy of IL-12
      therapy and to explore its mechanism of action. METHODS: Adult male A/J mice were
      subjected to 25% full-thickness scald or sham burn. Starting on day 3 after burn,
      groups of mice received five daily injections of IL-12, interferon-gamma (IFN
      gamma), or saline solution. Some animals received anti-IFN-gamma monoclonal
      antibody. At day 10 most animals underwent cecal ligation and puncture (CLP) and
      were observed for survival. Some animals were killed at day 10, and CD4-enriched
      splenocytes were stimulated with anti-CD3 antibody or concanavalin A and were
      studied for cytokine production and mRNA expression. RESULTS: IL-12 treatment, 25
      ng daily for 5 days, increased survival of the burn group after CLP to that of
      the sham burn control group. Anti-IFN-gamma antibody, 500 micrograms,
      administered 1 day before IL-12 treatment, reduced the efficacy of IL-12. IFN
      gamma treatment, 7000 units, moderately increased survival. IL-12 had no effect
      on survival of the sham burn group. At the time of CLP IL-12 therapy had induced
      a marked decrease in CD4+ lymphocyte IL-4 and a moderate increase in IFN-gamma
      production and mRNA expression without affecting IL-2. CONCLUSIONS: IL-12 is the
      most effective therapy so far tested in this burn plus CLP model. It acts at
      least in part through IFN-gamma. However, IFN-gamma therapy was not as effective
      as IL-12.

PMID- 8751596
TI  - Perception of breast cancer risk among women in breast center and primary care
      settings: correlation with age and family history of breast cancer.
AB  - BACKGROUND: A great deal of information about breast cancer risk is available to
      the public. The accuracy of impressions formed from this information is unknown.
      METHODS: A total of 750 women attending a breast center and 112 women attending a
      primary care office completed written surveys of their perceptions of average
      population risk, personal lifetime risk, and personal 10-year risk of getting
      breast cancer. Data sufficient to apply the Gail model were obtained, and a
      calculated estimate of risk was generated. Ratios of perceived to calculated risk
      were correlated with the respondent's age, family history of breast cancer, and
      location in a breast center or primary care office. RESULTS: Women in both
      practice settings overestimated population risk by more than twofold. Eighty
      percent overestimated personal lifetime risk by more than 50% and 35% by more
      than fivefold. Only 7% significantly underestimated risk. Ten-year risk estimates
      were even more inaccurate, with 69% overestimating risk by more than fivefold,
      46% by more than 10-fold, and 17% by more than 20-fold. Results from a primary
      care population were nearly identical. Women at the extremes of age were most
      inaccurate in estimating risk. It was surprising that family history had little
      impact on perception of personal risk. CONCLUSIONS: Women in both breast center
      and primary care settings have a fals:ly high perception of both short-term and
      long-term breast cancer risk. Health care providers should recognize these
      misconceptions and be aware that many women may benefit from risk counseling.

PMID- 8751597
TI  - Use of notebook computers for third-year surgical students.
AB  - BACKGROUND: Computer-aided instruction has become increasingly popular in medical
      education. Notebook computers (NCs) are attractive, convenient microcomputers. We
      hypothesized that use of NCs by third-year surgical students would enhance their
      performance of educational activities. METHODS: During the 1994-1995 academic
      year 25 student volunteers used NCs during the surgery clerkship. NC software
      included questions for self-examination, anatomy self-instruction program, word
      processing and electronic mail (e-mail) for recording and sending history and
      physicals (H & Ps) to faculty for review, and MEDLINE search software. Identical
      software was available to all students at on-campus computer centers. All
      students were asked to record the number of hours that they used the self
      examination and anatomy programs, number of H & Ps performed and reviewed by
      faculty, and number of literature searches performed. NC users were interviewed
      regarding the value of NC use and their rating of software programs. RESULTS: NC
      users (n = 25) used the self-examination and anatomy programs more often,
      performed more literature searches, and had a greater percentage of their H & Ps
      reviewed by faculty compared with non-NC users (n = 143) (p < 0.05 for all
      outcomes). Most NC users agreed that NC use was enjoyable and valuable, and they
      believed that all students should have NCs during the surgery clerkship. Students
      rated software in order of preference: e-mail > self-examination > MEDLINE search
      > anatomy program. CONCLUSIONS: NC use enhanced performance of educational
      activities in the surgery clerkship. Effort toward developing educational
      software for surgical students is warranted because students are likely to use
      such programs.

PMID- 8751598
TI  - Nitric oxide-associated regulation of hepatocyte glutathione synthesis is a
      guanylyl cyclase-independent event.
AB  - BACKGROUND: In a system of rat hepatocytes in primary culture, inhibition of
      cytokine-mediated nitric oxide (NO) production has been shown to be protective in
      states of oxidative stress. In the absence of oxidative injury, inhibition of NO
      synthesis has been associated with decreased intracellular levels of reduced
      glutathione. METHODS: To further characterize the role of NO in hepatocyte
      glutathione metabolism, cytokine-mediated NO synthesis was inhibited by addition
      of a competitive substrate inhibitor. Reduced glutathione, NO metabolites, and
      enzyme activity and steady-state mRNA levels of the rate-limiting enzyme for
      reduced glutathione (GSH) synthesis, gamma-glutamylcysteine synthetase, were
      determined in the presence and absence of the substrate inhibitor. A diffusible
      cyclic guanosine monophosphate (cGMP) analog, 8-bromo-cGMP, was added in selected
      instances to determine the potential role of soluble guanylyl cyclase in
      glutathione metabolism. RESULTS: Inhibition of cytokine-induced NO synthesis was
      associated with depletion of glutathione. These levels were restored in the
      presence of pharmacologic concentrations of a NO donor. Along with decreased
      glutathione levels, gamma-glutamylcysteine synthetase enzyme activity and steady
      state mRNA levels were also decreased with inhibition of NO synthesis. Addition
      of 8-bromo-cGMP did not alter glutathione content or gamma-glutamylcysteine
      synthetase enzyme activity and steady-state mRNA levels. CONCLUSIONS: In this
      system of cultured rat hepatocytes, cytokine-mediated NO synthesis may be
      protective in states of oxidative stress through regulation of glutathione
      synthesis.

PMID- 8751599
TI  - Vascular inducible nitric oxide synthase gene therapy: requirement for guanosine
      triphosphate cyclohydrolase I.
AB  - BACKGROUND: Human inducible nitric oxide synthase (iNOS) gene transfer inhibits
      myointimal hyperplasia in vitro. However, unstimulated vascular smooth muscle
      cells (SMC) do not synthesize tetrahydrobiopterin (BH4), an essential cofactor
      for iNOS, which may be an obstacle to successful vascular iNOS gene therapy. We
      investigated the capacity of gene transfer of guanosine triphosphate (GTP)
      cyclohydrolase I (GTPCH), the rate-limiting enzyme for BH4 biosynthesis, to
      supply cofactor for iNOS activity. METHODS: A human GTPCH expression plasmid
      (pCIS-GTPCH) was transfected into rat aortic SMC (RAOSMC) and BH4-deficient
      NIH3T3 cells engineered to stably express human iNOS (3T3-iNOS). GTPCH activity
      and intracellular biopterins were assessed as a measure of successful
      transfection, and the capacity of GTPCH to reconstitute iNOS activity was used to
      determine whether BH4 was made available to the iNOS protein. RESULTS: The pCIS
      GTPCH-transfected 3T3 cells had demonstrable GTPCH activity as compared with
      control cells (169.3 +/- 6.6 pmol/hr/mg versus 0, p < 0.001). Intracellular
      biopterin levels were also increased in transfected 3T3 and SMC (60.6 +/- 2.6 and
      101.7 +/- 28.3 pmol/mg, respectively, versus less than 4 in control cells). GTPCH
      reconstituted near-maximal iNOS activity in 3T3-iNOS cells despite a gene
      transfer efficiency of less than 1%. GTPCH and iNOS enzymes did not have to
      coexist in the same cell for the synthesized BH4 to support iNOS activity.
      CONCLUSION: GTPCH gene transfer reconstitutes iNOS activity in BH4-deficient
      cells despite poor transfer efficiency. GTPCH can deliver a cofactor to targeted
      cells even if it is synthesized in neighboring cells, and may be a means to
      concurrently deliver BH4 with iNOS in vivo.

PMID- 8751600
TI  - Nitric oxide regulates insulin secretion in the isolated perfused human pancreas
      via a cholinergic mechanism.
AB  - BACKGROUND: The purpose of this study was to determine whether nitric oxide
      regulates insulin secretion in the isolated perfused human pancreas. METHODS:
      Single-pass perfusion was performed in four pancreata with a modified Krebs
      medium. Sequential 10-minute infusions (separated by 10-minute basal periods) of
      (1) 25 nmol/L acetylcholine, (2) 2.5 mumol/L acetylcholine, and (3) 16.7 mmol/L
      glucose were initially infused. Then 0.1 mumol/L of NG-monomethyl-L-arginine
      (NMMA) was infused during a period of 10 minutes, and steps (1) through (3) were
      repeated. The change in insulin secretion from basal levels during each
      stimulation was calculated and compared with that seen after NMMA infusion.
      RESULTS: Infusion of 25 nmol/L and 2.5 mumol/L acetylcholine resulted in a
      significant stimulation of insulin secretion before NMMA infusion (p < 0.05) and
      after NMMA infusion for acetylcholine at 25 nmol/L (p < 0.05). There was a
      significant decrease in acetylcholine-induced insulin secretion after NMMA
      infusion for acetylcholine at 25 nmol/L and 2.5 mumol/L compared with before NMMA
      infusion (p < 0.05). Infusion of 16.7 mmol/L glucose significantly stimulated
      insulin secretion before and after NMMA infusion, but there was no significant
      difference seen with insulin secretion before and after NMMA infusion. Insulin
      secretion was significantly inhibited during NMMA infusion (p < 0.05).
      CONCLUSIONS: These data show that infusion of the nitric oxide synthase inhibitor
      NMMA suppressed cholinergic-stimulated insulin secretion but did not affect
      glucose-stimulated insulin secretion. We conclude that nitric oxide regulates
      insulin secretion in the isolated perfused human pancreas.

PMID- 8751601
TI  - Effects of diabetes and uremia on mesenteric vascular reactivity.
AB  - BACKGROUND: Diabetes and uremia are comorbid conditions that have significant
      effects on cardiovascular physiology. These studies were designed to examine the
      effects of diabetes and uremia on vascular reactivity. METHODS: Sprague-Dawley
      rats were divided into control (C), diabetic (D), uremic (U), and diabetic/uremic
      (D + U) groups. Diabetes (D, D + U groups) was induced with an injection of
      streptozotocin. Uremic (U, D + U groups) was produced by seven-eighths
      nephrectomy. Serum glucose, blood urea nitrogen, creatinine, creatinine
      clearance, and protein excretion were measured at baseline and before
      microvascular studies at 4 or 8 weeks after injection. Vascular reactivity was
      studied in isolated, pressurized, and superfused segments of mesenteric
      arterioles (300 microns). Changes in internal vessel diameter were measured in
      response to phenylephrine (10(-8) to 10(-4) mol/L), acetylcholine (10(-9) to 10(
      5) mol/L), and nitroprusside (10(-9) to 10(-2) mol/L). RESULTS: Results at 4 and
      8 weeks were similar in all groups. Vasoconstrictor responses to phenylephrine
      and endothelium-independent vasodilator responses to nitroprusside were not
      altered in any experimental group. Endothelium-dependent vasodilator responses to
      acetylcholine were significantly depressed in both diabetic groups (D and D + U,
      p < 0.01 versus control), and there were no differences between the two diabetic
      groups. CONCLUSIONS: Streptozotocin-induced diabetes results in impairment of
      endothelial-dependent (nitric oxide mediated) vasodilator responses in mesenteric
      resistance vessels, which are unaffected by coexisting uremia. Uremia has little
      effect on mesenteric vascular reactivity in this model.

PMID- 8751602
TI  - Calcium-dependent second-messenger regulation of low-density lipoprotein
      oxidation by human aortic smooth muscle cells.
AB  - BACKGROUND: We postulated that the response of vascular smooth muscle cells
      (SMCs) to oxidized low-density lipoprotein (LDL) may be modulated through calcium
      and 3', 5' cyclic adenosine monophosphate (Ca+2-cAMP) second-messenger activity.
      METHODS: Changes in cytosolic calcium [Ca+2]i in aortic SMCs exposed to native (N
      ) and oxidized (Ox-) LDL were measured with a Fura 2-AM indicator. The influence
      of cAMP on this response was determined by incubating the cells with either
      forskolin or 8-bromo-cAMP (stimulatory) or galanin (inhibitory). The cells were
      then activated by an initial preincubation with N- or Ox-LDL, and the subsequent
      cellular oxidation of N-LDL was measured. The effect of cAMP mediators alone or
      in conjunction with calcium antagonism was studied. RESULTS: Exposure of SMCs to
      Ox-LDL resulted in a marked elevation of [Ca+2]i(306 +/- 12 nmol/L) compared with
      that in the control group (192 +/- 15 nmol/Liter; p < 10(-6)). This response was
      augmented by cAMP stimulation (406 +/- 8 nmol/L; p < 10(-6)) but reduced by cAMP
      inhibition (247 +/- 8 nmol/L; p < 10(-6)). The activation of intracellular
      signaling by initial Ox-LDL priming increased the subsequent oxidation of N-LDL
      (0.40 +/- 0.02 nmol malondialdehyde versus 0.24 +/- 0.02 nmol MDA control; p <
      10(-4)). This response was enhanced by cAMP (0.45 +/- 0.03 nmol MDA; p < 10(-4))
      and inhibited by galanin (0.26 +/- 0.02; p < 10(-4)). The cAMP effect was
      reversed by the blockade of calcium mobilization via membrane channels and
      reticular release. CONCLUSIONS: Oxidized LDL-induced Ca+2-cAMP signaling
      modulates the cellular oxidation of N-LDL. This finding suggests a mechanism
      through which the scavenger uptake of modified LDL may potentially be regulated.

PMID- 8751603
TI  - The obligate role of protein kinase C in mediating clinically accessible cardiac
      preconditioning.
AB  - BACKGROUND: Cardiac preconditioning is an adaptation of cardiomyocytes that
      promotes tolerance to a subsequent ischemic insult. Adenosine receptor signaling
      is proposed as a mediator of preconditioning, but its mechanism of protection
      remains unknown. We hypothesized that protection against hypoxia-reoxygenation
      (H/R) injury could be conferred in a rat ventricle by adenosine-mediated protein
      kinase C (PKC) activation and that adenosine-mediated cardioprotection could be
      extended to human ventricular muscle. METHODS: Isolated rat and human ventricular
      muscle (VM) strips were subjected to 30 minutes of hypoxia and 60 minutes of
      reoxygenation (H/R control). The VM was pretreated with 125 mumol/L adenosine, an
      adenosine antagonist ((p-Sulfophenyl) theophylline [SPT] 50 mumol/L) and
      adenosine (adenosine + SPT), or with a PKC inhibitor (chelerythrine, 10 mumol/L)
      and adenosine (adenosine + chelerythrine) before H/R Developed force (DF) and
      tissue creatine kinase (CK) activity were assessed at end reoxygenation. Human
      trabeculae were obtained from diseased explanted hearts at cardiac
      transplantation and were also subjected to H/R injury. Human VM was pretreated
      with adenosine (125 mumol/L) before H/R injury. Results are expressed as mean +/-
      standard error of mean. RESULTS: In the rat, adenosine pretreatment conferred
      protection of DF against H/R injury (adenosine, 62% +/- 6%; H/R control, 27% +/-
      2%, p < 0.05). Adenosine + SPT or adenosine + chelerythrine eliminated the
      functional recovery conferred by adenosine. This recovery of contractile function
      was associated with greater tissue CK activity (adenosine, 415 +/- 40 units/gm;
      H/R control, 78 +/- 13 units/gm, p < 0.05). The protective effects of adenosine
      against H/R were present in the human ventricle and with recovery of DF in
      adenosine (66% +/- 5%) and H/R control (24% +/- 4%), p < 0.05. CONCLUSIONS:
      Adenosine, a clinically accessible agonist, induces protection against H/R injury
      through a PKC-mediated mechanism in the rat ventricle. Further, the protection
      conferred by adenosine against H/R extends to the human ventricle.

PMID- 8751604
TI  - Elevation of intracellular cyclic adenosine monophosphate inhibits the epidermal
      growth factor signal transduction pathway and cellular growth in pancreatic
      adenocarcinoma cell lines.
AB  - BACKGROUND: The epidermal growth factor (EGF) signal transduction pathway,
      frequently activated in pancreatic cancer, is an important regulator of cellular
      growth and transformation. This study examined whether activation of the cyclic
      adenosine monophosphate protein kinase A pathway may inhibit the EGF signal
      transduction pathway in pancreatic cancer cell lines. METHODS: Human pancreatic
      cancer lines BxPC-3 and AsPC-1 were stimulated with EGF, forskolin, or both.
      Forskolin is a compound that increases cyclic adenosine monophosphate levels.
      Assays of cell lines were then obtained for cellular growth (MTT assay),
      anchorage-independent growth (soft agar), and EGF-induced mitogen-activated
      protein kinase activation as measured by an in-gel kinase assay. RESULTS:
      Treatment with forskolin resulted in inhibition of EGF-induced activation of
      mitogen-activated protein kinase activity (BxPC-3 78% inhibition and AsPC-1 70%
      inhibition, p < 0.005), diminished cellular proliferation (BxPC-3 92% inhibition
      and AsPC-1 86% inhibition, p < 0.001), and formation of colonies in soft agar
      (BxPC-3 98% inhibition and AsPC-1 76% inhibition, p < 0.001). Forskolin did not
      inhibit EGF receptor autophosphorylation or tyrosine kinase signaling in response
      to EGF. CONCLUSIONS: Forskolin-induced inhibition of mitogen-activated protein
      kinase is associated with diminished pancreatic cancer cell proliferation in
      vitro. Use of strategies to increase cyclic adenosine monophosphate levels may
      have therapeutic application in pancreatic cancer.

PMID- 8751605
TI  - Diethylmaleate attenuates endotoxin-induced lung injury.
AB  - BACKGROUND: Alterations in the cellular redox state play a critical role in cell
      signaling and cell activation, suggesting that administration of sulfhydryl
      reactive agents may have important modulatory effects on the inflammatory
      response. We postulated that intracellular thiol depletion may attenuate the
      pulmonary inflammatory response after intratracheal administration of endotoxin
      (LPS) and that this attenuation would supersede the reduction in antioxidant
      defenses associated with depletion of the endogenous antioxidant, glutathione.
      METHODS: Sprague Dawley rats were administered diethylmaleate (6 mmol/kg
      intraperitoneally), a rapidly acting glutathione-depleting agent, followed by
      intratracheal administration of LPS. Lung injury was assessed by measuring the
      transpulmonary flux of 125-I albumin and expressed as a permeability index.
      RESULTS: Administration of diethylmaleate reduced lung glutathione levels from
      1310 +/- 114 to 185 +/- 48 nmol/gm. This was associated with a reduction in the
      permeability index after LPS treatment (LPS, 0.22 +/- 0.03 versus LPS +
      diethylmaleate, 0.03 +/- 0.01). Bronchoalveolar lavage fluid polymorphonuclear
      neutrophil counts were markedly reduced in animals pretreated with diethylmaleate
      (LPS, 90.5 +/- 24 x 10(6) versus LPS + diethylmaleate, 1.9 +/- 0.4 x 10(6)).
      Peripheral blood polymorphonuclear neutrophils isolated from animals treated with
      diethylmaleate had equivalent chemotactic responses to n-formyl-methionyl-leucyl
      phenylalanine and normal up-regulation of CD11b as determined by flow cytometry.
      Levels of bronchoalveolar lavage fluid tumor necrosis factor-alpha were
      unaffected. CONCLUSIONS: Diethylmaleate attenuates LPS-induced lung injury
      through a reduction in lung polymorphonuclear neutrophil sequestration. Normal
      peripheral blood neutrophil chemotactic responses and CD11b expression suggest
      that thiol depletion might mediate this effect through inhibition of endothelial
      cell adhesion molecule activity.

PMID- 8751606
TI  - Pentoxifylline maintains vascular endothelial cell function during hyperdynamic
      and hypodynamic sepsis.
AB  - BACKGROUND: Although pentoxifylline produces various beneficial effects after
      endotoxemia or sepsis occurs, it is not known whether this agent attenuates the
      depressed endothelial cell function during sepsis. Therefore the aim of this
      study was to determine whether pentoxifylline maintains vascular endothelial cell
      function (i.e., improves the release of endothelium-derived nitric oxide) during
      hyperdynamic and hypodynamic stages of polymicrobial sepsis. METHODS: Rats were
      subjected to sepsis by cecal ligation and puncture (CLP), after which 3 ml/100 gm
      body wt normal saline solution was injected subcutaneously in these and rats in a
      sham-operated group. At 1 hour after the onset of sepsis, pentoxifylline (50
      mg/kg body wt) or an equal volume of normal saline solution was infused
      intravenously during a 30 minute period. At 10 and 20 hours after CLP was
      performed (10-hour CLP, hyperdynamic sepsis; 20-hour CLP, hypodynamic sepsis),
      the thoracic aorta was isolated, cut into rings, and placed in organ chambers.
      Norepinephrine (2 x 10(-7) mol/L) was used to achieve near maximal tension. Dose
      responses for an endothelium-dependent vasodilator, acetylcholine, and an
      endothelium-independent vasodilator, nitroglycerine, were carried out. The
      changes in percentage relaxation in the aortic rings by these agonists were then
      determined. RESULTS: Endothelium-dependent (acetylcholine-induced) vascular
      relaxation decreased significantly at 10 and 20 hours after CLP. Administration
      of pentoxifylline, however, maintained acetylcholine-induced vascular relaxation
      at both time points. In contrast, no significant reduction in nitroglycerine
      induced vascular relaxation was seen in rats with sepsis irrespective of
      pentoxifylline treatment. CONCLUSIONS: Because pentoxifylline prevented
      endothelial cell dysfunction at 10 and 20 hours after CLP occurred, this agent
      appears to be a useful agent for maintaining vascular endothelial function during
      the hyperdynamic and hypodynamic stages of polymicrobial sepsis.

PMID- 8751607
TI  - Injury induces rapid changes in hepatocyte nuclear factor-1: DNA binding.
AB  - BACKGROUND: Transcriptional regulation in the liver plays a critical role in
      mediating the acute phase response to injury. The molecular mechanisms driving
      these transcriptional events, however, are poorly defined in vivo. The liver
      specific transcription factor hepatocyte nuclear factor (HNF)-1 binds to the 5'
      upstream region of many acute phase genes. To explore the connection between
      injury and transcriptional regulatory mechanisms, we investigated the effect of
      injury on HNF-1 binding activity. METHODS: Liver nuclear extracts were prepared
      from animals after burn or anesthetized sham burn injury. HNF-1 binding activity,
      affinity, and off rate were assessed by electrophoretic mobility shift analysis.
      RESULTS: HNF-1 binding activity decreased by 28% 1 1/2 hours after injury. The
      dissociation constant for HNF-1 increased from 0.6 nm to 11.8 nm at 1 1/2 hours
      after burn injury partly because of an increase in off rate for the HNF-1: DNA
      complex. CONCLUSIONS: Burn injury leads to a significant decrease in HNF-1
      binding activity as a result of decreased affinity of HNF-1 for DNA. These injury
      induced alterations in binding of a liver-specific transcription factor for its
      DNA binding site represent a mechanism for rapidly modulating acute phase gene
      transcription in vivo.

PMID- 8751608
TI  - Hypoxemia/reoxygenation down-regulates interleukin-8-stimulated bactericidal
      activity of polymorphonuclear neutrophil by differential regulation of CD16 and
      CD35 mRNA expression.
AB  - BACKGROUND: The purpose of this study was to determine the effects of
      hypoxemia/reoxygenation (H/R) on the regulation of interleukin-8 (IL-8)
      stimulated human polymorphonuclear neutrophil (PMN) bactericidal activity.
      METHODS: Venous human whole blood was rendered normoxic (Pvo2 saturation 60% to
      80%), hypoxemic (Pvo2 saturation, less than 15%), or H/R (Pvo2 saturation more
      than 97%) by dialyzing the blood against a gas mixture of N2/H2/CO2 +/- 30% O2.
      Two hundred microliter aliquots from each study group were incubated with IL-8
      (50 ng/ml) for 45 minutes before fluorescein isothiocyanate-conjugated mouse
      antihuman CD16 or CD35 antibodies were added. Bactericidal activity was measured
      with the release of 51Cr from labeled bacteria at 1:1, 5:1, and 10:1 PMN-target
      ratios. Steady-state mRNA levels for CD16 and CD35 were quantified by Northern
      blot analyses. RESULTS: H/R reduced PMN bactericidal activity compared with
      hypoxemic levels for staphylococcus aureus (48 +/- 5.6 versus 27 +/- 3.3) and
      Escherichia coli (58 +/- 7.1 versus 33 +/- 4.2). H/R reduced the surface
      expression of CD16 but not CD35 (mean channel fluorescence CD16, 610 +/- 70
      versus 310 +/- 30 for hypoxemia versus H/R; p < 0.01). After H/R was performed,
      IL-8 decreased mRNA levels for CD16 but not for CD35 compared with levels seen
      during hypoxemia + IL-8. CONCLUSIONS: H/R down-regulates IL-8-stimulated PMN
      bactericidal activity by decreasing steady-state mRNA levels and surface
      expression of CD16. PMN bactericidal capability after H/R + IL-8 is primarily
      complementary and not Fc gamma receptor dependent.

PMID- 8751609
TI  - Sepsis increases endocytosis of endotoxin into hepatocytes.
AB  - BACKGROUND: Chylomicrons bind endotoxins and accelerate their clearance from
      plasma to the liver. This results in reduced mortality from septic shock in a
      rodent model. We hypothesized that the clearance of the LPS-chylomicron (LPS-CM)
      complex by hepatocytes is due to receptor-mediated endocytosis and that sepsis up
      regulates this process. METHODS: Three groups of Sprague-Dawley rats; (1)
      control; (2) pretreated with 10 micrograms/kg LPS 24 hours before treatment; and
      (3) pretreated with 17-alpha-ethinyl estradiol (EE, 5 mg/kg subcutaneously for 3
      days), were infused with labeled I125-LPS alone or with I125-LPS bound to
      chylomicron. Livers were removed 2.5, 15, and 30 minutes after LPS injection, and
      hepatic endosomes were isolated from the liver homogenates by serial
      ultracentrifugation in sucrose gradients. RESULTS: The injection of I125-LPS-CM
      complexes resulted in higher levels of endosomal I125-LPS in all groups, as
      compared with I125-LPS alone. In addition, the endosomal uptake of I125-LPS was
      markedly increased by both LPS and EE pretreatments. CONCLUSIONS: These data
      strongly suggest a primary role for receptor-mediated endocytosis in the
      increased clearance of LPS when bound to chylomicron. In addition, exposure to
      LPS appears to increase the accumulation of LPS in endosomes by a mechanism
      similar to that of EE, which is known to up-regulate receptor-mediated
      lipoprotein uptake. This endogenous pathway for the catabolism of endotoxins may
      provide a teleological explanation for the hypertriglyceridemia observed during
      sepsis.

PMID- 8751610
TI  - Soluble intercellular adhesion molecule-1 provokes polymorphonuclear leukocyte
      elastase release by CD18.
AB  - BACKGROUND: Elevated levels of soluble intercellular adhesion molecule-1 (sICAM
      1) correlate with the development of postinjury multiple organ failure. Soluble
      ICAM-1 secretion is known to be induced in endothelial cells and monocytes by
      diverse inflammatory stimuli. We have found that incubation of quiescent
      polymorphonuclear leukocytes (PMNs) with sICAM-1 elicits elastase release and,
      more recently, that cross-linking CD18 receptors on PMNs also produces elastase
      release. Consequently, our study hypothesis was that sICAM-1 provokes PMN
      elastase release through its interaction with CD18. METHODS: To obtain sICAM-1,
      Chinese hamster ovarian cells transfected with human ICAM-1 were lysed and
      centrifuged at 150,000 g for 1 hour; the supernatant was passed over an ICAM-1
      affinity column, eluted with 0.1 mmol/L glycine HCl, and concentrated with
      dialysis filter. Human PMNs (2.5 x 10(5)) were saturated with specific monoclonal
      antibodies for the beta 2 subunits (CD11a, CD11b, CD18) or nonspecific monoclonal
      antibodies for 30 minutes on ice before a 1-hour incubation with sICAM-1 (75
      ng/ml) at 37 degrees C. Elastase activity was measured by the cleavage of n
      methoxysuccinyl-A-A-P-V-p-nitroanilide. RESULTS: Neutrophil incubation with sICAM
      1 resulted in 19.2% +/- 2.8% of total PMN elastase, compared with 2.4% +/- 0.5%
      in the controls. Blockade of CD18 abrogated sICAM-1 provoked elastase release
      with monoclonal antibodies to CD18 (TS1/18, 31H8) resulting in 4.3% +/- 1.0% and
      5.5% +/- 1.4% elastase release, respectively. Blockade of CD11a, CD11b, and
      nonspecific antibody controls had no effect on sICAM-1 induced elastase release.
      CONCLUSIONS: In vitro, sICAM-1 provokes PMN elastase release through CD18. This
      may represent a mechanism by which elevated levels of circulating sICAM-1,
      released from local injury sites, provoke distal organ dysfunction.

PMID- 8751612
TI  - Cytokine-induced increases in endothelial permeability occur after adhesion
      molecule expression.
AB  - BACKGROUND: Transmigration of neutrophils (PMNs) through endothelial cell tight
      junctions is a critical stage in the tissue injury of ischemia-reperfusion (I/R).
      Although cytokines are released in I/R, it is unclear whether cytokines directly
      increase permeability or this phenomenon requires both expression of cell
      adhesion molecules and PMN adhesion-activation. METHODS: We exposed confluent
      monolayers of human umbilical vein endothelial cells to physiologic
      concentrations of interleukin-1 (10 pg/ml) and tumor necrosis factor-alpha (10
      pg/ml) in the absence of PMNs. Tight junction permeability was quantified with
      both transendothelial electrical resistance and albumin flux, whereas expression
      of endothelial-leukocyte adhesion molecule-1 was measured by flow cytometry (t
      test p < 0.05). RESULTS: Stimulation with tumor necrosis factor-alpha or
      interleukin-1 produced maximal transendothelial electrical resistance decreases
      at 12 hours with return to baseline at 24 hours. Increases in albumin flux began
      at 6 hours, with maximum effects at 24 hours. These changes occurred soon after
      maximal expression of endothelial-leukocyte adhesion molecule-1 at 4 hours.
      CONCLUSIONS: Cytokines induced increases in both cell adhesion molecule
      expression and endothelial permeability. This sequence of events is consistent
      with direct cytokine effects on cytoarchitecture, because it occurred without the
      adhesion-activation of PMNs.

PMID- 8751611
TI  - Metallothionein and HSP-72 are induced in the liver by hemorrhagic shock and
      resuscitation but not by shock alone.
AB  - BACKGROUND: Previous reports have indicated that HSP-72 and metallothionein mRNA
      undergo induction in the liver after resuscitated hemorrhagic shock. In this
      study we investigated whether unresuscitated shock triggers induction and whether
      protein induction also occurs. METHODS: Rats were subjected to resuscitated and
      unresuscitated shock protocols of varying severity; livers were isolated and
      processed for Northern, Western, and immunohistochemical analysis. Cadmium
      binding assay was used to measure metallothionein protein. RESULTS:
      Unresuscitated shock led to no induction of HSP-72 or metallothionein. Severe
      resuscitated shock led to prompt induction of HSP-72 mRNA and protein in
      hepatocytes, up to 20-fold over sham group; metallothionein mRNA induction
      appeared later than HSP-72 and did not lead to elevated protein levels. Mild
      resuscitated shock had little effect. CONCLUSIONS: These findings indicate
      resuscitated severe shock, not shock alone, leads to induction of HSP-72 and
      metallothionein in the liver. Metallothionein expression lags behind HSP-72
      expression.

PMID- 8751613
TI  - Endothelial cells modulate smooth muscle cell morphology by inhibition of
      transforming growth factor-beta 1 activation.
AB  - BACKGROUND: We have previously demonstrated in a coculture model that endothelial
      cells (ECs) exert regulatory control over smooth muscle cell (SMC) morphology.
      This study was performed to test the hypothesis that ECs inhibit transforming
      growth factor-beta 2 (TGF-beta 1) activation through the release of plasminogen
      activator inhibitor (PAI-1). METHODS: Bovine SMCs were cultured on a thin,
      semipermeable membrane, either alone or opposite ECs in coculture (SMC/EC).
      Conditioned media and cell lysates at 1, 5, and 21 days were assayed for TGF-beta
      1 and PAI-1 by enzyme-linked immunoabsorbent assay. Cell proliferation rates,
      protein, and DNA content were measured and compared with SMC morphology. RESULTS:
      Activation of TGF-beta 1 was significantly decreased (1.2% versus 18.9% active
      TGF-beta 1 p < 0.05) and PAI-1 was increased (659 pg/ml versus 343 pg/ml p <
      0.05) in SMC/EC medium on day 1, compared with the medium of SMC alone.
      Significantly higher levels of PAI-1 were measured in cell lysates of cocultured
      ECs (128 pg/micrograms DNA) than in cocultured SMCs (5.8 pg/micrograms DNA, p <
      0.05). SMC/EC coculture prevented the SMC hill-and-valley growth morphology seen
      in SMCs cultured alone. CONCLUSIONS: In a model designed to study SMC/EC
      interactions, it was seen that ECs can alter growth characteristics of SMCs by
      producing PAI-1, which interferes with the plasminogen pathway of TGF-beta 1
      activation. This suggests that reduced EC PAI-1 production could play a role in
      alteration of SMC phenotype in vivo.

PMID- 8751614
TI  - Differential effects of platelet-derived growth factor isotypes on human smooth
      muscle cell proliferation and migration are mediated by distinct signaling
      pathways.
AB  - BACKGROUND: Platelet-derived growth factor (PDGF) is a potent mitogen and
      chemoattractant for vascular smooth muscle cells (SMCs). Three isotypes of PDGF
      (BB, AB, and AA) have been identified; each of these isotypes may have differing
      effects on the behaviour of vascular SMCs. In this study we evaluated the
      influence of PDGF isotypes on proliferation and migration of human venous SMCs
      and explored the signaling pathways through which these effects are mediated.
      METHODS: Proliferation was measured by a 72-hour assay of cell number, and
      migration was evaluated by a 4-hour microchemotaxis assay. The effects of PDGF
      isotypes on the activities of the signaling proteins mitogen-activated protein
      kinase (MAP-K), p 125 focal adhesion kinase (p125FAK), and tensin were measured
      by immunoprecipitation of these proteins and subsequent phosphorylation on myelin
      basic protein (in MAP-K) and Western blotting with antiphosphotyrosine (in tensin
      and p125FAK). RESULTS: All three isotypes stimulated SMC proliferation (PDGF-BB >
      AB > AA). PDGF-BB and -AB, but not -AA, stimulated chemotaxis. All three isotypes
      activated MAP-K with an intensity that corresponded to their proliferative
      effects. PDGF-BB and -AB tyrosine phosphorylated tensin and p125FAK, whereas PDGF
      AA had no effect on either of these proteins. CONCLUSIONS: For human vascular
      SMCs the physiologic effects and the signaling pathways that mediate these
      effects are specific for each of the three PDGF isotypes. These data also suggest
      an association between MAP-K and SMC proliferation and between the proteins,
      p125FAK and tensin, and migration.

PMID- 8751615
TI  - Vascular endothelial growth factor and heparin in a biologic glue promotes human
      aortic endothelial cell proliferation with aortic smooth muscle cell inhibition.
AB  - BACKGROUND: Incomplete luminal endothelialization may contribute to small
      diameter vascular graft failure. Vascular endothelial growth factor (VEGF) can be
      used to stimulate endothelialization without provoking smooth muscle cell (SMC)
      proliferation. Heparin and VEGF in a fibrin glue (FG) were investigated for their
      ability to promote selective human aortic endothelial cell (HAEC) proliferation
      and human aortic smooth muscle cell (HASMC) inhibition. METHODS: HAECs and HASMCs
      were seeded on FG containing VEGF (2.5, 10, 30, 100 ng/ml) or VEGF and heparin
      (5, 50, 500 units/ml). Proliferation assays were performed with tritiated
      thymidine on days 1 and 3. Results were analyzed by ANOVA, with p < or = 0.05
      significant. RESULTS: HAEC proliferation on FG with 10, 30, and 100 ng/ml VEGF
      was significantly greater than FG alone at days 1 and 3. The addition of 50
      units/ml heparin to VEGF significantly increased HAEC proliferation to greater
      than FG with VEGF alone at day 1. Human aortic SMC proliferation was not
      stimulated by the addition of VEGF. The addition of 5, 50, and 500 units/ml
      heparin significantly inhibited HASMC proliferation regardless of VEGF
      concentration. DISCUSSION: VEGF at 10 ng/ml combined with heparin at 50 units/ml
      exhibited maximal stimulation of HAECs with inhibition of HASMCs. VEGF and
      heparin in a biologic glue may improve patency by selectively promoting HAEC
      proliferation without HASMC growth on synthetic vascular bypass grafts.

PMID- 8751616
TI  - Butyrate inhibits seeding and growth of colorectal metastases to the liver in
      mice.
AB  - BACKGROUND: The short-chain fatty acid butyrate inhibits growth of colorectal
      carcinoma cells in vitro. Mevalonate, a short-chain fatty acid structurally and
      metabolically related to butyrate, is important in signal transduction and is
      essential for cell growth. We investigated butyrate's effects on seeding and
      growth of colorectal tumor cells metastatic to the liver in vivo and hypothesized
      that butyrate's antiproliferative effects are associated with inhibition of
      mevalonate-mediated cell growth. METHODS: Hepatic metastases were induced by
      injecting 1 x 10(5) MC-26 (N-methyl-N-nitrosourea-induced murine colorectal
      carcinoma) cells into the spleen of BALB/c mice. Mice were treated with a
      continuous intravenous infusion of butyrate (2 gm/kg/day) for 7 days starting 24
      hours before tumor cells were injected. Study variables included liver weight and
      number of hepatic surface metastases. Proliferation studies on MC-26 cells were
      performed in vitro to examine the effects of butyrate alone or combined with
      mevalonate or mevastatin (an inhibitor of mevalonate synthesis). RESULTS:
      Butyrate reduced seeding and growth of colorectal tumor cells in vivo. Mevalonate
      diminished butyrate's antiproliferative action in vitro, whereas mevastatin
      potentiated this effect. CONCLUSIONS: These studies (1) show that butyrate
      inhibits seeding and growth of hepatic colorectal metastases in vivo, (2)
      associate butyrate's antiproliferative effects with inhibition of mevalonate
      mediated cell growth, and (3) indicate that 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitors may have synergistic antiproliferative effects when combined
      with butyrate.

PMID- 8751617
TI  - Inhibition of breast cancer progression by an antibody to a thrombospondin-1
      receptor.
AB  - BACKGROUND: Thrombospondin-1 (TSP-1) is a matrix-bound adhesive glycoprotein.
      Breast carcinoma cells exhibit increased expression of a novel TSP-1 receptor. We
      evaluated the role of this receptor in breast cancer adhesion and progression.
      METHODS: Adhesion assays were performed to evaluate MDA-MB-231 breast cancer cell
      adhesion to TSP-1 in vitro in the presence of either nonimmune immunoglobulin
      G(IgG) or anti-TSP-1 receptor IgG. Receptor-mediated tumor cell progression was
      evaluated in athymic nude mice. Mice were inoculated with MDA-MB-231 breast
      cancer cells and randomized to treatment with intraperitoneal injections of
      saline solution, nonspecific IgG antibody, or an anti-TSP-1 receptor antibody
      every other day for 20 days. Mice were killed at 21 days. The peritoneal cavity
      was examined grossly for primary tumor implantation. The liver and lungs were
      examined histologically for micrometastases. RESULTS: MDA-MB-231 breast cancer
      cells adhered to TSP-1 in vitro. This adhesion was inhibited to 10% of control by
      anti-TSP-1 receptor antibody (p < 0.005). Anti-TSP-1 receptor antibody inhibited
      in vivo breast cancer progression. Mice treated with control IgG antibody or
      saline solution alone exhibited extensive intraperitoneal seeding. Only one mouse
      treated with the anti-TSP-1 receptor antibody exhibited any intraperitoneal tumor
      seeding (p < 0.01). CONCLUSIONS: These data suggest that TSP-1 and its receptor
      play an important role in breast cancer progression.

PMID- 8751618
TI  - Posterior transpetrosal approach to aneurysms of the basilar trunk and
      vertebrobasilar junction.
AB  - Aneurysms of the basilar trunk and vertebrobasilar junction represent an
      exceptional challenge to the neurosurgeon. Surgical access to these deep and
      confined lesions is hampered by the direct proximity of highly vulnerable neural
      structures such as the brainstem and cranial nerves, as well as by the structure
      of the petrous bone, which blocks direct surgical approach to these aneurysms. A
      number of surgical tactics consisting of different supra- and infratentorial
      approaches have been applied over the years to gain access to these treacherous
      lesions. Only recently have lateral approaches, such as the anterior
      transpetrosal, the retrolabyrinthine-transsigmoidal, and the combined
      supra/infratentorial-posterior transpetrosal approaches, directed through parts
      of the petrous bone, been reported for surgery of basilar trunk and
      vertebrobasilar junction aneurysms. Because detailed reports of direct operative
      intervention using the transpetrosal route for these rare and difficult lesions
      are scarce, the authors present their surgical experiences in nine patients with
      basilar trunk and vertebrobasilar junction aneurysms, in whom they operated via
      the supra/infratentorial-posterior transpetrosal approach. In eight patients,
      including one with a giant partially thrombosed basilar trunk aneurysm, direct
      clipping of the aneurysm via the transpetrosal route was possible. In one patient
      with a giant vertebrobasilar junction aneurysm, the completely calcified aneurysm
      sac was resected after occlusion of the vertebral artery. In total, one patient
      died and another experienced postoperative accentuation of preexisting cranial
      nerve deficits. Two patients had transient cerebrospinal fluid leakage, and the
      postoperative course was uneventful in the remaining seven. Postoperative
      angiography demonstrated complete aneurysm clipping in eight patients and relief
      of preoperative brainstem compression in the patient with the giant
      vertebrobasilar junction aneurysm. It is concluded that the supra/infratentorial
      posterior transpetrosal approach allows excellent access to the basilar artery
      trunk and vertebrobasilar junction and can be considered the approach of choice
      to selected aneurysms located in this area.

PMID- 8751619
TI  - Use of a split dura for revascularization of ischemic hemispheres in moyamoya
      disease.
AB  - A new technique of indirect revascularization using the dural arterial supply to
      provide donor vessels is presented together with the results of an assay
      performed to determine the angiogenic activity of the dura. At surgery, a portion
      of the dura near the branches of the middle meningeal artery was split into outer
      and inner layers, and the split surface of the outer layer was attached to the
      cortical surface. This procedure, combined a with standard
      encephaloduroarteriosynangiosis, was applied to 25 hemispheres in 18 patients
      with pediatric moyamoya disease (mean age 6 years). All of the patients were
      symptom free by 1.5 years after surgery. The follow-up period ranged from 1 to 12
      years (mean 6.5 years). Thirteen (81%) of 16 patients were able to lead normal
      lives and three were mildly handicapped due to mental retardation that existed
      preoperatively. Postoperative superselective angiograms demonstrated effective
      cortical revascularization through the dural arteries as well as from the scalp
      arteries. A histological study of the dura in cases of moyamoya disease showed an
      increased number of blood vessels in the outer layer. Angiogenic activity
      determined by chorioallantoic membrane assay was higher in the split surface of
      the dura than in the internal surface of the dura (the natural interface between
      the dura and cortex). The split duroencephalosynangiosis described in this report
      is a useful addition to indirect revascularization techniques, allowing extension
      of the area of revascularization in the ischemic hemispheres of patients with
      moyamoya disease.

PMID- 8751620
TI  - Clinical significance of the flow gap in carotid magnetic resonance angiography.
AB  - Magnetic resonance (MR) angiography offers a safe, noninvasive alternative to
      conventional angiography in patients with suspected carotid stenosis; however, it
      tends to overestimate the severity of stenosis. Loss of the MR signal with a
      resulting flow gap is a frequent finding in cases of high-grade stenosis. The
      authors undertook this study to define the range of carotid stenosis associated
      with a flow gap on two-dimensional time-of-flight (2DTF)-MR angiography. Blinded
      evaluations were made of 102 common carotid bifurcations in 51 patients who had
      undergone both conventional angiography and 2DTF-MR angiography. The percent of
      diameter stenosis was calculated from the conventional angiogram using the method
      adopted by the Asymptomatic Carotid Atherosclerosis Study (ACAS) trial. An MR
      flow gap was noted if there was a segment of the vessel that was completely free
      of signal with a reappearance of the signal distally. According to conventional
      angiography, the minimum percentage of stenosis associated with a flow gap is
      56%. Flow gaps were present in 20 of 22 arteries (sensitivity 91%) with stenosis
      of 60% or more and in two of the 66 arteries (specificity 97%) with less than 60%
      stenosis. Flow gaps were present in all arteries with stenosis of 70% or more.
      Complete occlusion was correctly identified in 10 of 10 cases. These results
      demonstrate that the presence of a flow gap on 2DTF-MR angiography is a reliable
      marker of clinically significant carotid stenosis (measuring 60% or more), with
      sensitivity and specificity comparable to duplex carotid ultrasound. In addition,
      MR angiography can be used to screen the intracranial circulation for significant
      vascular pathology in patients being considered for carotid endarterectomy.

PMID- 8751621
TI  - Predicting length of hospital stay and cost by aneurysm grade on admission.
AB  - To determine the relationship between clinical grade on admission and treatment
      cost after aneurysm rupture, the authors retrospectively examined the length of
      hospital stay (LOS) and total hospitalization costs (excluding professional fees)
      for 543 patients admitted for aneurysm surgery between 1983 and 1993. The overall
      median LOS was 18 days, with a range of 1 to 165 days. Increased median LOS
      correlated with Hunt and Hess Grades 0 to IV on admission (p < 0.001). Median LOS
      for Grade V patients was reduced, in part, because of early mortality. Increased
      treatment cost also correlated with worse admission clinical grade (p < 0.001). A
      significant proportion of total expenditures occurred early in the
      hospitalization for patients in all clinical grades. Identification of additional
      factors affecting the cost of aneurysm treatment is indicated to complement
      treatment outcome studies.

PMID- 8751622
TI  - Terson's syndrome in spontaneous subarachnoid hemorrhage: a prospective study in
      60 consecutive patients.
AB  - Sixty consecutive patients with spontaneous subarachnoid hemorrhage (SAH) were
      prospectively studied by means of indirect funduscopy to address the question of
      incidence and prognostic implications of Terson's syndrome (TS) after SAH.
      Terson's syndrome was diagnosed in 10 (16.7%) of 60 patients and was associated
      with subarachnoid rebleeding in seven of 10. No correlation was found between
      anatomical localization of the ruptured aneurysm and TS laterality. Case fatality
      was nine (90%) of 10 in patients with TS compared to five (10%) of 50 in non-TS
      patients. It is concluded that TS is not infrequent (16.7%) in spontaneous SAH
      and has a poor prognosis, often heralding subarachnoid rebleeding.

PMID- 8751623
TI  - Superselective intraarterial papaverine administration: effect on regional
      cerebral blood flow in patients with arteriovenous malformations.
AB  - In this study the authors determined the effect of papaverine on regional
      cerebral blood flow (rCBF) in the angiographically normal arteriolar beds of
      patients with arteriovenous malformations (AVMs) who underwent transfemoral
      superselective angiography. Middle cerebral artery (MCA) branch vessels were
      catheterized during 10 procedures performed in nine patients. The mean (+/-
      standard deviation) largest AVM diameter was 4.4 +/- 1 cm. Regional CBF was
      measured by recording the washout of a bolus of xenon-133 injected through the
      microcatheter. In a dose-ranging study. rCBF and MCA pressure in two patients
      were repeatedly measured after 3-minute infusions of papaverine at 0.07, 0.7, and
      7 mg/minute. In a single-dose study, an additional eight patients received only
      the highest dose of papaverine administered over a 3-minute period. In the dose
      ranging study, CBF increased from baseline in a dose-dependent fashion. In the
      single-dose study, papaverine increased in rCBF 103%, from 48 +/- 11 to 95 +/- 23
      ml/100 g/minute at an MCA pressure of 55 +/- 23 mm Hg. Increase in rCBF was
      linearly related (y = 2.2x - 17, r2 = 0.84; p = 0.001) to baseline MCA pressure
      (range 22-84 mm Hg). Papaverine increases rCBF in a direct proportion to baseline
      MCA pressure, even at low baseline pressures. Selective infusion of vasodilators
      should be investigated in acute cerebral hypotension to facilitate either primary
      or collateral recruitment of CBF by aiding spontaneous autoregulatory
      vasodilation. In addition, rCBF monitoring may be useful in determining the most
      effective intraarterial dose of papaverine while minimizing complications due to
      hyperemia.

PMID- 8751624
TI  - Hospital resource utilization in the treatment of cerebral aneurysms.
AB  - The authors reviewed clinical and financial data for all patients treated for
      nontraumatic subarachnoid hemorrhage (SAH) and unruptured cerebral aneurysms at
      their institution between June 1993 and December 1994. This study sought to
      identify specific areas of high resource utilization that may be amenable to
      reduction of expenditures without compromising quality of care. Detailed hospital
      financial data were correlated with clinical grade and course. Areas of high
      resource use were identified based on patient charges and category-specific
      loaded hospital cost. Patients were divided into four groups: Group 1, surgically
      treated unruptured aneurysms (28 patients); Group 2, acute SAH (42 patients);
      Group 3, SAH with vasospasm (32 patients); and Group 4, SAH with negative
      angiogram (10 patients). Total cost per patient (mean +/- standard deviation in
      thousands of U.S. dollars) was highest for Group 3 (38.4 +/- 21.3; vs. Group 1,
      12.7 +/- 8.8; Group 2, 22.6 +/- 20.9; and Group 4, 25.0 +/- 33.5) and correlated
      with hospital length of stay, Hunt and Hess grade, and Fisher grade. Areas of
      highest hospital cost were not always reflected in patient charges. The three
      areas of highest cost accounted for 48.5% of the total cost and were: 1)
      intensive care unit (ICU) room (Group 1, 2.5 +/- 3.5; Group 2, 7.0 +/- 9.2; Group
      3, 11.0 +/- 7.8; and Group 4, 7.9 +/- 14.1); 2) arteriography (Group 1, 1.7 +/-
      1.2; Group 2, 2.1 +/- 1.5; Group 3, 4.1 +/- 2.1; and Group 4, 2.2 +/- 0.7); and
      3) ICU medicosurgical supplies (Group 1, 1.7 +/- 0.8; Group 2, 2.0 +/- 1.5; Group
      3, 3.7 +/- 1.7; and Group 4, 2.0 +/- 3.0). It is concluded that cost containment
      strategies should be based on cost rather than charge and novel approaches will
      be required to reduce the cost of treating patients with SAH. Such approaches
      might include preventing vasospasm, reducing ICU stay, selective use of
      arteriography, and reducing the cost of supplies.

PMID- 8751625
TI  - Age and outcome after aneurysmal subarachnoid hemorrhage: why do older patients
      fare worse?
AB  - Advanced age is a recognized prognostic indicator of poor outcome after
      subarachnoid hemorrhage (SAH). The relationship of age to other prognostic
      factors and outcome was evaluated using data from the multicenter randomized
      trial of nicardipine in SAH conducted in 21 neurosurgical centers in North
      America. Among the 906 patients who were studied, five different age groups were
      considered: 40 years or less, 41 to 50, 51 to 60, 61 to 70, and more than 71
      years. Twenty-three percent of the individuals enrolled were older than 60 years
      of age. Women outnumbered men in all age groups. Level of consciousness (p =
      0.0002) and World Federation of Neurological Surgeons grade (p = 0.0001) at
      admission worsened with advancing age. Age was also related to the presence of a
      thick subarachnoid clot (p = 0.0001), intraventricular hemorrhage (p = 0.0003),
      and hydrocephalus (p = 0.0001) on an admission computerized tomography scan. The
      rebleeding rate increased from 4.5% in the youngest age group to 16.4% in
      patients more than 70 years of age (p = 0.002). As expected, preexisting medical
      conditions, such as diabetes (p = 0.028), hypertension (p = 0.0001), and
      pulmonary (p = 0.0084), myocardial (p = 0.0001), and cerebrovascular diseases (p
      = 0.0001), were positively associated with age. There were no age-related
      differences in the day of admission following SAH, timing of the surgery and/or
      location, and size (small vs. large) of the ruptured aneurysm. During the
      treatment period, the incidence of severe complications (that is, those
      complications considered life threatening by the reporting investigator)
      increased with advancing age, occurring in 28%, 33%, 36%, 40%, and 46% of the
      patients in each advancing age group, respectively (p = 0.0002). No differences
      were observed in the reported frequency of surgical complications. No age-related
      differences were found in the overall incidence of angiographic vasospasm;
      however, symptomatic vasospasm was more frequently reported in the older age
      groups (p = 0.01). Overall outcome, assessed using the Glasgow Outcome Scale at 3
      months post-SAH, was poorer with advancing age (p < 0.001). Multivariate analysis
      of overall outcome, adjusting for the different prognostic factors, did not
      remove the age effect, which suggests that the aging brain has a less optimal
      response to the initial bleeding. Age as a risk factor is a continuum; however,
      there seems to be a significant increased risk of poor outcome after the age of
      60 years.

PMID- 8751627
TI  - Experience with use of extended length peritoneal shunt catheters.
AB  - The placement of a ventriculoperitoneal (VP) shunt is the current treatment of
      choice for diversion of cerebrospinal fluid associated with hydrocephalus.
      Although there are a host of reported potential abdominal complications related
      to the procedure, they are notably uncommon. The authors report their experience
      with the primary insertion of an extended length open-ended peritoneal tubing
      (120 cm) undertaken expressly to avoid the need for a lengthening procedure
      because of growth of the patient. In a review of new insertions of VP shunts
      using the extended length tubing over a 14-year period at Childrens Hospital of
      Los Angeles, a total 998 shunts were placed in 952 patients, with a mean follow
      up period of 6.7 years. The patients experienced a total of 52 distal shunt
      revisions for a variety of malfunction etiologies. In patients ranging in age
      from premature neonate to 20 years, there was no increase in the distal
      complication rate, and specifically no complications were experienced that were
      directly related to the use of the extended length tubing. The authors conclude
      that the use of an extended length peritoneal shunt catheter is not associated
      with an increase in complications and eliminates the need to lengthen the
      peritoneal catheter for growth of the patient.

PMID- 8751626
TI  - Ventriculostomy infections: the effect of monitoring duration and catheter
      exchange in 584 patients.
AB  - The investigators undertook a retrospective analysis of ventriculostomy
      infections to evaluate their relationship to monitoring duration and prophylactic
      catheter exchange. In 1984, the results of an epidemiological study of
      ventriculostomy-related infection were published. One of the conclusions of the
      paper was that the incidence of ventriculostomy-related infections rose after 5
      days of monitoring. This led to the recommendation that catheters be
      prophylactically changed at 5-day intervals if prolonged monitoring was required.
      A recent randomized prospective study on central venous catheters showed no
      reduction in infection with prophylactic catheter exchanges. This has led the
      authors to reexamine their experience with ventriculostomy infections. Data on
      584 severely head injured patients with ventriculostomies were prospectively
      collected in two data banks, The Traumatic Coma Data Bank and The Medical College
      of Virginia Neurocore Data Bank. These data were retrospectively analyzed for
      factors associated with ventriculostomy related infections. It was found that
      there is a relationship of ventriculitis to monitoring duration but it is not
      simple or linear. There is a rising risk of infection over the first 10 days, but
      infection then becomes very unlikely despite a population that continues to be at
      risk. Patients in whom catheters were replaced prior to 5 days did not have a
      lower infection rate than those whose catheters were exchanged at more than 5-day
      intervals. Based on these data, it is recommended that ventriculostomy catheters
      for intracranial pressure monitoring be removed as quickly as possible, and in
      circumstances in which prolonged monitoring is required, there appears to be no
      benefit from catheter exchange.

PMID- 8751628
TI  - Quantitative analysis of cerebrospinal fluid spaces in children with occipital
      plagiocephaly.
AB  - The etiology of occipital plagiocephaly (OP) is not fully understood. The authors
      have observed that many infants with this condition have external hydrocephalus.
      This study was undertaken to quantify cerebrospinal fluid (CSF) space caliber in
      children with OP and to compare these measurements to those derived from normal
      age-matched controls to further elucidate the pathogenesis of this condition.
      Thirty-one infants with isolated unilateral OP (mean age 6 months) were studied.
      Infants with multiple cranial suture abnormalities, impaired neurological
      function, developmental delay, and associated craniofacial anomalies were
      excluded. Twenty normal infants were evaluated as controls. The volumes of the
      sylvian fissures, frontal and occipital subarachnoid spaces, as well as the cross
      sectional areas of the suprasellar and perimesencephalic cisterns, were
      calculated from computerized tomography (CT) studies. Ventricular size was also
      assessed. Generalized subarachnoid space dilation was observed in 29 (93.5%) of
      the 31 children with OP. Head circumference was significantly greater in the case
      group (71.4 vs. 50.8 percentile; p = 0.0002 by analysis of variance). The sylvian
      fissure volume was significantly larger in the case group (5.8 ml vs. 0.7 ml in
      controls, p < 0.0001). The volume of the contralateral sylvian fissure was
      greater than that ipsilateral to the side of OP (7.1 ml vs. 4.5 ml, p = 0.001).
      Frontal subarachnoid space volume was greater in infants with OP (27.5 ml vs. 0.6
      ml in controls, p < 0.0001). Both the suprasellar and perimesencephalic cisterns
      were of greater caliber in the case group (p = 0.007 and p < 0.0001,
      respectively). No difference in ventricular size or occipital subarachnoid space
      volume was noted between groups. The extraventricular CSF spaces in
      neurologically unimpaired infants with OP are significantly larger than those in
      age- and sex-matched controls. Enlarged subarachnoid spaces may increase the
      compliance and malleability of the calvaria and sutures, predisposing to
      positional deformity. External hydrocephalus may be a fundamental etiological
      factor in OP.

PMID- 8751629
TI  - Are peripheral neurectomies of value in the treatment of trigeminal neuralgia? An
      analysis of new cases and cases involving previous radiofrequency gasserian
      thermocoagulation.
AB  - The indications, advantages, complications, and benefits of peripheral neurectomy
      in patients with trigeminal neuralgia were studied in detail in 40 patients
      treated between 1982 and 1991. Twenty-eight patients had previously received
      radiofrequency thermocoagulation: peripheral neurectomy was performed for pain
      recurrence. These patients had excellent or good pain relief for at least 5 years
      postsurgery. Of the 12 patients who had peripheral neurectomy as their only
      procedure, seven had an excellent result and five had a good result. Five of the
      patients had recurrence of pain after 2 years but responded well to a second
      neurectomy. Elderly patients who experienced pain in the first and second
      divisions of the trigeminal distributions were the best candidates. Peripheral
      neurectomy is an effective, safe procedure for elderly patients who suffer from
      trigeminal neuralgia and have a limited life span.

PMID- 8751630
TI  - Indications and results of combined anterior-posterior approaches for spine tumor
      surgery.
AB  - Spinal instrumentation currently allows gross-total resection and reconstruction
      in cases of malignancies at all levels of the spine. The authors analyzed the
      results in 110 patients who underwent surgery for primary and metastatic spinal
      tumors over a 5-year period (1989-1993) at a single institution. Major primary
      sites of tumor included breast (14 cases), chordoma (14 cases), lung (12 cases),
      kidney (11 cases), sarcoma (13 cases), plasmacytoma (10 cases), and others (36
      cases). Prior to surgery, 55 patients (50%) had received prior treatment. Forty
      eight patients (44%) were nonambulatory, and severe paraparesis was present in 20
      patients. Fifty-three patients (48%) underwent combined anterior-posterior
      resection and instrumentation. 33 (30%) underwent anterior resection with
      instrumentation, 18 (16%) underwent anterior or posterior resection alone, and
      the remaining six patients (5%) underwent posterior resection and
      instrumentation. Major indications for anterior-posterior resection included
      three-column involvement, high-grade instability, involvement of contiguous
      vertebral bodies, and solitary metastases. Postoperatively, 90 patients improved
      neurologically. The overall median survival was 16 months, with 46% of patients
      surviving 2 years. Fifty-three patients (48%) suffered postoperative
      complications. Despite the high incidence of complications, the majority of
      patients reported improvement in their quality of life at follow-up review. Our
      findings suggest that half of all patients with spinal malignancies require
      combined anterior-posterior surgery for adequate tumor removal and stabilization.

PMID- 8751631
TI  - Bilateral multilevel laminectomy with or without posterolateral fusion for
      cervical spondylotic myelopathy: relationship to type of onset and time until
      operation.
AB  - The authors retrospectively evaluated the relationship of several preoperative
      factors in 69 patients who had myelopathy due to multilevel cervical spondylosis
      without ossification of the posterior longitudinal ligament treated with Kirita's
      bilateral wide laminectomy. In 34 patients with focal instability or
      malalignments, posterolateral fusion was also combined. The clinical results at
      an average follow-up period of 3.5 years (range 1-10 years) after operation in
      the groups that had and had not undergone fusion were equally satisfactory, and
      preoperative focal instability was believed to be the sole useful indication for
      adding posterolateral fusion. The patients were classified in three groups
      according to the acuteness of the onset. The type of onset and time until
      operation were found to be the factors most strongly related to prognosis, and
      clinical outcome was correlated with the duration after onset when plotted as
      days in the acute, months in the subacute, and years in the insidious onset
      groups. Wide laminectomy with or without posterolateral fusion is a simple
      operation that is recommended, provided that it is performed early enough
      according to the type of onset.

PMID- 8751632
TI  - Chronic intrathecal delivery of baclofen by a programmable pump for the treatment
      of severe spasticity.
AB  - The aim of this study was to determine the efficacy, safety, and cost
      effectiveness of intrathecal baclofen delivered by a programmable pump for the
      chronic treatment of severe spasticity. Sixty-six patients with severe spasticity
      of spinal cord origin that was refractory to oral baclofen or who experienced
      intolerable side effects with this form of the drug were screened. The first nine
      participated in a double-blinded, randomized, placebo (normal saline)-controlled
      trial to determine response to a bolus dose of intrathecal baclofen. Subsequent
      patients were enrolled in an open-label treatment protocol without a placebo
      trial. All passed the screening, and the pump was implanted in 59 patients.
      Spasticity scores and medical costs before and after surgery were analyzed. In
      all patients, the mean Ashworth score for rigidity decreased from 4.3
      preoperatively to 1.4 (p < 0.0005) with use of intrathecal baclofen. The spasm
      frequency score decreased from a mean of 3.6 to 0.5 (p < 0.0005). Activities of
      daily living, sleep, and skin integrity improved, and pain was eradicated in
      some. Constipation occurred in six patients. A reduction in dosage was
      necessitated by muscular hypotonia in three ambulatory patients, areflexic
      bladder and urinary retention in three others, and nausea, dizziness, and
      drowsiness in one. Catheter-related problems occurred 19 times in 15 patients.
      One pump was explanted because of infection in the pump pocket, and one was
      removed after it eroded through the skin. There were no pump failures. The use of
      intrathecal baclofen resulted in a decrease in the average length of subsequent
      hospitalizations. It is concluded that intrathecal baclofen delivered by an
      implanted programmable pump is a safe, effective, and cost-efficient method for
      treatment of severe intractable spinal spasticity.

PMID- 8751633
TI  - Long-term effects of continuous intrathecal opioid treatment in chronic pain of
      nonmalignant etiology.
AB  - In the present retrospective investigation, the long-term effects of continuous
      intrathecal opioid therapy via implantable infusion pump systems were examined in
      120 patients with chronic, nonmalignant pain syndromes. The follow-up period was
      6 months to 5.7 years (mean 3.4 years +/- 1.3 standard error of the mean).
      Deafferentation pain and neuropathic pain showed the best long-term results, with
      68% and 62% pain reduction (visual analog scale), respectively. The mean morphine
      dosage initially administered was 2.7 mg/day (range 0.3-12 mg/day); after an
      average of 3.4 years, it was 4.7 mg/day (range 0.3-12 mg/day). In a long-term
      observation of 28 patients who received intrathecal morphine for longer than 4
      years. 18 patients (64.3%) had a constant dosage history and 10 patients (35.7%)
      showed an increase in morphine dosage to more than 6 mg/day 1 year after dosage
      determination. In seven cases, a tolerance developed: in four patients the
      tolerance was controlled by means of "drug holidays"; but in three patients it
      was necessary to remove the pump systems. Explantation of the pump system
      occurred in 22 additional cases for other reasons. Throughout the follow-up
      period, 74.2% of the patients profited from the intrathecal opiate therapy: the
      average pain reduction after 6 months was 67.4% and, as of the last follow-up
      examination, it was 58.1%. Ninety-two percent of the patients were satisfied with
      the therapy and 81% reported an improvement in their quality of life. The
      authors' 6-year experience with administration of intrathecal opioid medications
      for nonmalignant pain should encourage the use of this method in carefully
      selected patients.

PMID- 8751634
TI  - Activation of the complement cascade and increase of clusterin in the brain
      following a cortical contusion in the adult rat.
AB  - The aim of the present study was to examine the glial cell response and the
      possible involvement of the complement cascade following a cerebral cortical
      contusion. The lesion was produced using a standardized weight-drop technique in
      adult rats. The blood-brain barrier was damaged, as demonstrated by a decrease of
      immunoreactivity for a tight junction protein normally expressed by endothelial
      cells of small vessels in the central nervous system. Increased immunoreactivity
      for microglial (OX42) and astroglial cells (glial fibrillary acidic protein), as
      well as macrophages expressing ED1-immunoreactivity (IR) were found in the
      vicinity of the lesion at all postoperative survival times (2-14 days). In the
      present study complement factor C3d- and C9-IR was found around the lesion,
      indicating that activation of the complement cascade had taken place.
      Furthermore, immunoreactivity for the putative complement inhibitor clusterin
      (sulfated glycoprotein-2) was found in some of the injured neurons. The
      contralateral hemisphere showed no evidence of the reaction found in the
      ipsilateral hemisphere. The balance between complement activation and complement
      inhibitors may have an impact on the degenerative components in the brain
      following traumatic injury and in particular on the events leading to nerve cell
      death.

PMID- 8751635
TI  - Blood-brain barrier breach following cortical contusion in the rat.
AB  - Adult Fisher 344 rats were subjected to a unilateral impact to the dorsal cortex
      above the hippocampus at 3.5 m/second, resulting in a 2-mm cortical depression.
      This caused severe cortical damage and neuronal loss in hippocampus subfields
      CA1, CA3, and hilus. Breakdown of the blood-brain barrier (BBB) was assessed by
      injecting the protein horseradish peroxidase (HRP) 5 minutes prior to or at
      various times after injury (5 minutes, 1, 3, 6, and 12 hours, 1, 2, 5, and 10
      days). Animals were killed 1 hour after HRP injection and brain sections were
      reacted with diaminobenzidine to visualize extravascular accumulation of the
      protein. Maximum staining occurred in animals injected with HRP 5 minutes prior
      to or 5 minutes after cortical contusion. Staining at these time points was
      observed in the ipsilateral cortex of the impact area and areas adjacent to it,
      as well as in the ipsilateral hippocampus. Some modest staining occurred in the
      dorsal contralateral cortex near the superior sagittal sinus. Cortical HRP
      staining gradually decreased at increasing time intervals postinjury. By 10 days,
      no HRP staining was observed in any area of the brain. In the ipsilateral
      hippocampus, HRP staining was absent by 3 hours postinjury and remained so at the
      6- and 12-hour time points. Surprisingly, HRP staining was again observed in the
      ipsilateral hippocampus 1 and 2 days after cortical contusion, indicating a
      biphasic opening of the BBB following head trauma and a possible second wave of
      secondary brain damage days after the contusion injury. These data indicate that
      regions not initially destroyed by cortical impact, but evidencing BBB breach,
      may be accessible to neurotrophic factors administered intravenously both
      immediately and days after brain trauma.

PMID- 8751636
TI  - The Q10 ratio for basal cerebral metabolic rate for oxygen in rats.
AB  - Previously the authors showed that hypothermia exerts a greater effect on the
      cerebral metabolic rate for oxygen (CMRO2) that is associated with the
      maintenance of cellular viability, or "basal" CMRO2, than on electroencephalogram
      (EEG)-associated CMRO2 or "functional" CMRO2. On the basis of their findings, the
      authors hypothesized that the ratio of CMRO2 over a 10 degrees C temperature
      range (Q10) for basal CMRO2 was greater than that for functional and total CMRO2.
      They tested their hypothesis by determining the Q10 for basal CMRO2 from 38
      degrees C to 28 degrees C. They measured whole-brain cerebral blood flow (CBF)
      and CMRO2 in six rats during progressive hypothermia at a brain temperature of 38
      degrees C and, after induction of an isoelectric EEG signal (50 microV/cm) with
      thiopental sodium, they repeated the measurements at 38 degrees C, 34 degrees C,
      30 degrees C, and 28 degrees C. In a control group (five rats), six sequential
      measurements of CBF and CMRO2 were made while the animals were anesthetized by
      0.5% isoflurane/70% N2O/30% O2 at a brain temperature of 38 degrees C over a time
      span equivalent to the hypothermic group, that is, approximately 3 hours. The Q10
      for basal CMRO2 calculated over 38 degrees C to 28 degrees C was 5.2 +/- 0.92.
      However, the decrease in basal CMRO2 between 38 degrees C and 28 degrees C was
      nonlinear on a log plot, revealing a two-component response: a high temperature
      sensitivity component between 38 degrees C and 30 degrees C with a Q10 of 12.1,
      and a lower temperature sensitivity component between 30 degrees C and 28 degrees
      C with a Q10 of 2.8. The combined overall Q10 for basal CMRO2 between 38 degrees
      and 28 degrees C was 5.2. The energy-requiring processes associated with these
      high and low temperature sensitivity components of basal CMRO2 have yet to be
      identified.

PMID- 8751637
TI  - Microsurgically produced bifurcation aneurysms in a rabbit model for endovascular
      coil embolization.
AB  - The authors present a detailed account of the microsurgical production of
      bifurcation aneurysms in chinchilla rabbits for basic studies of endovascular
      coil embolization of aneurysms. End-to-side anastomoses of both common carotid
      arteries (CCAs) were performed, and a venous pouch was fitted into the newly
      created bifurcation. These experimental aneurysms closely mimic human cerebral
      aneurysms in size and hemodynamic features. Sixty-three animals underwent
      operation. Fifteen animals died in the course of the experiment and 15 were
      excluded because of a CCA occlusion within the carotid bifurcation. Electrical
      detachable platinum coils, also known as Guglielmi detachable coils (GDCs), and
      tungsten mechanical detachable coils (MDCs) were used for the endovascular
      occlusion of 26 bifurcation aneurysms (16 rabbits were treated with GDCs and 10
      with MDCs). Initially, complete angiographic obliteration (95%-100% occlusion of
      the aneurysm) was achieved in nine rabbits and incomplete obliteration (< 95%
      occlusion) was seen in 17 animals. Final angiography 3 to 6 months later
      demonstrated complete occlusion in only four and partial occlusion in 22
      aneurysms. At present, the histopathological examination of 17 embolized
      aneurysms has revealed incomplete obliteration of all aneurysms, even in those
      three cases that were thought to be completely embolized according to
      angiographic criteria. A general overestimation of the radiological degree of
      aneurysm obliteration was found.

PMID- 8751638
TI  - Reconstruction of the posterior inferior cerebellar artery in the treatment of
      giant aneurysms. Report of two cases.
AB  - Two techniques of revascularizing the posterior inferior cerebellar artery (PICA)
      during aneurysm surgery are presented. One involves transposition of the PICA to
      the vertebral artery proximal to the aneurysm using a superior temporal artery
      (STA) as a graft. This is used in cases in which the PICA has branched off from
      the wall of the giant vertebral artery aneurysm. The other technique involves end
      to-end anastomosis of the PICA after excision of a giant distal PICA aneurysm
      located at the cranial loop near the roof of the fourth ventricle. The
      reconstructions of the PICA described here are surgical procedures designed to
      preserve normal blood flow in the PICA in patients treated for giant aneurysms
      involving that artery.

PMID- 8751639
TI  - Aneurysm formation and rupture at the site of anastomosis following bypass
      surgery. Case report.
AB  - Four years after undergoing a superficial temporal artery-middle cerebral artery
      bypass procedure, this patient presented with a ruptured aneurysm at the
      anastomosis site. The ruptured aneurysm caused subarachnoid and intracerebral
      hemorrhages and was treated by surgically clipping its neck. Characteristics of
      the aneurysm included: 1) a relatively large size (8 x 6 x 6 mm): 2) a thickened
      wall; 3) a location apart from the suture line; 4) a projection in a direction
      consistent with hemodynamic stress; and 5) a time interval from bypass surgery to
      rupture that lasted 4 years. These features, along with the well-known fact that
      hemodynamic stress can cause aneurysms, led the authors to believe that this
      aneurysm was a true one. The authors present a case of this unusual complication
      following bypass surgery and provide a brief review of the literature.

PMID- 8751640
TI  - Giant intracranial aneurysm and fibromuscular dysplasia in an adolescent with
      alpha 1-antitrypsin deficiency.
AB  - Recent studies have suggested that a deficiency of alpha 1-antitrypsin may be a
      genetic risk factor for the development of intracranial aneurysms and arterial
      fibromuscular dysplasia. The authors report a 16-year-old girl with a history of
      lung disease who suffered a cerebral hemorrhage due to the rupture of a giant
      intracranial aneurysm arising from the middle cerebral artery. This fusiform
      aneurysm was associated with fibromuscular dysplasia of the intimal type. She was
      found to have an unusual alpha 1-antitrypsin deficiency (PiMP phenotype). This
      case provides further evidence of an underlying arteriopathy in alpha 1
      antitrypsin deficiency.

PMID- 8751641
TI  - Rotational obstruction of nondominant vertebral artery and ischemia. Case report.
AB  - A 70-year-old man presented with repeated vertebrobasilar insufficiency for 3
      years. Four-vessel angiography revealed complete occlusion of the nondominant
      left vertebral artery on head turning to the right. Three-dimensional
      computerized tomography angiography demonstrated atlantoaxial joint dislocation
      when the head was turned to the right, in accordance with simultaneous occlusion
      of the left vertebral artery caused by stretching of the artery at C1-2. After
      posterior fixation of C1-2 by a Halifax interlaminar fixation system, the patient
      had no further episodes. Hemodynamic function associated with nondominant
      vertebral artery occlusion contributed to the symptoms in this case.

PMID- 8751642
TI  - Idiopathic orbital inflammation with intracranial extension. Case report.
AB  - Idiopathic orbital inflammation or orbital pseudotumor with intracranial
      extension is a rare condition. It consists of a nonspecific infiltrate of the
      fatty tissue of the orbit that extends through one or more foramina into the
      adjacent intracranial tissue. The lesion mimics an infectious or neoplastic
      lesion. The authors present a case involving the youngest patient yet reported
      with the broadest intracranial extension. Only 17 previous cases have been
      reported. The principal symptoms include decreased visual acuity and proptosis.
      Extension commonly develops through the superior orbital fissure into the middle
      cranial fossa and the cavernous sinus. The initial treatment is a regimen of high
      dose steroids, with radiotherapy given in unresponsive cases.

PMID- 8751643
TI  - A surgical technique to avoid postoperative enophthalmos in the cranioorbital
      approach. Technical note.
AB  - The authors describe a surgical technique to avoid postoperative enophthalmos
      when using the cranioorbital approach. To perform osteotomies with a less
      demanding technique, two separate bone flaps were created: 1) a free
      frontotemporal bone flap and 2) en bloc removal of the superior and lateral
      orbital rims: Because the latter bone flap includes both the orbital roof and the
      posterolateral wall of the orbit with the greater wing of the sphenoid bone,
      unnecessary bone defects in the lateral orbital wall are avoided. The technique
      has been performed in seven patients treated for medially located skull base
      neoplasms or complex anterior circulation aneurysms without postoperative
      enophthalmos or other cosmetic problems. The authors believe this cranioorbital
      approach, with its simpler, less invasive surgical technique, offers a definite
      advantage by avoiding postoperative enophthalmos.

PMID- 8751645
TI  - Early postoperative neuroimaging.

PMID- 8751644
TI  - Bridged craniotomy for stable fixation of a bone flap. Technical note.
AB  - Postoperative depression of the bone flap is a common and bothersome problem in
      craniotomies. In this paper, a simple technique to avoid this deformity is
      described. The key to this technique is to leave uncut a part of each osteotomy
      approximately 5 mm in width as a "bridge" to the bone flap, which is then
      subsequently cut with the aid of a chisel. This technique provides stable
      fixation of the bone flap and satisfactory cosmetic results with little
      additional operating time.

PMID- 8751646
TI  - Forestier's disease.

PMID- 8751647
TI  - Anterior cervical foraminotomy.

PMID- 8751648
TI  - Anterior cervical foraminotomy.

PMID- 8751649
TI  - Villonodular synovitis.

PMID- 8751650
TI  - Parkinson's disease.

PMID- 8751652
TI  - Of towerites, trenches, and troglodytes.

PMID- 8751653
TI  - A history of radiology and radiation oncology at Thomas Jefferson University.
AB  - The Departments of Radiology and Radiation Oncology have evolved during the last
      100 years from a small combined facility into two large comprehensive departments
      characterized by the highest quality of patient care. Both departments, now under
      the direction of David C. Levin and Walter J. Curran, Jr., are leaders in
      graduate education and research productivity. As a result, both departments
      clearly represent another golden age in the history of radiology at Thomas
      Jefferson University.

PMID- 8751654
TI  - Coauthors' contributions to major papers published in the AJR: frequency of
      undeserved coauthorship.
AB  - OBJECTIVE: Over half of the major papers published in the American Journal of
      Roentgenology (AJR) have five or more coauthors. This project was designed to
      evaluate the specific contributions of coauthors and the prevalence of undeserved
      authorship in major papers from institutions in the United States. MATERIALS AND
      METHODS: Questionnaires were mailed to the first author of 275 major papers from
      institutions in the United States that were published in the AJR in 1992 and
      1993. Questions focused on coauthors' contributions to research design, data
      collection, data analysis, and manuscript preparation, and on undeserving
      authorship. RESULTS: One hundred ninety-six (72%) of the surveys were returned.
      Ninety-nine percent of first authors, 75% of second authors, fewer than half of
      third authors, and one third of fourth authors and beyond were said to have
      contributed to at least three of the following: research design, data collection,
      data analysis, and manuscript preparation (p < .02). A strong correlation was
      indicated between authorship position and contribution (r = -.69, p < .001), with
      a mean overall contribution of 63 +/- 17% (mean +/- SD) for the first author, 20
      +/- 12% for the second author, 10 +/- 7% for the third author, 7 +/- 6% for the
      fourth author, and 5 +/- 5% for all other authors. Coauthors were listed in
      decreasing order of contribution in 70% of articles. However, the last author was
      the second major contributor in 10% of articles with three or more authors. The
      incidence of "undeserved" coauthors increased from 9% on papers with three
      authors to 30% on papers with more than six authors (mean, 17%; r = .97; p <
      .001). Undeserved authorship was attributed largely to individuals who
      contributed only cases (29%) or who created a sense of obligation or fear in the
      first author (40%). Manuscripts were more likely to include an undeserved
      coauthor when the first author was a nontenured staff member (45%) than when he
      or she was tenured faculty (28%) (p < .02). When decision about authorship were
      made at project conception, there were fewer coauthors (3.9 versus 5.4, p < .02)
      and a lower incidence of manuscripts with undeserving coauthors (23% versus 47%,
      p < .01). The final manuscript was read by all coauthors in 80% of manuscripts,
      and all coauthors were thought to understand the manuscript to the extent they
      could publicly defend it in 78% of manuscripts. The most commonly cited reason
      that otherwise honest individuals accept undeserved authorship was academic
      promotion. CONCLUSION: Undeserved authorship is a common and serious problem that
      is motivated primarily by academic promotion policies. The first two authors are
      said to account for the preponderance of work in almost all major papers.

PMID- 8751655
TI  - Three-dimensional CT: real-time interactive volume rendering.

PMID- 8751656
TI  - A nuclear medicine review manual on the Internet.

PMID- 8751657
TI  - Malpractice issues in radiology. Perceptual errors.

PMID- 8751658
TI  - Diagnostic radiologists' nonhospital practices: high-technology and other
      characteristics of radiology offices.

PMID- 8751659
TI  - Distinction of masses involving the sella and suprasellar space: specificity of
      imaging features.

PMID- 8751660
TI  - Staging of arteriovenous malformations using three-dimensional time-of-flight MR
      angiography and volume-rendered displays of surface anatomy.

PMID- 8751661
TI  - Reconstructive myofascial skull-base flaps: normal appearance on CT and MR
      imaging studies.
AB  - On imaging studies, the tendon and fractured coronoid process are clues to the
      presence of a temporalis myofascial flap. A large, bulky muscle and subcutaneous
      fat are characteristic of a free flap with microvascular anastomosis. The
      enhancing, thin, curvilinear pericranial flap bridges an osseous defect of the
      anterior skull base. Familiarity with these features is essential to avoid
      misdiagnosis of normal flap as tumor and to identify tumor recurrence.

PMID- 8751662
TI  - Plain radiographic and MR imaging appearances of familial dermal cylindroma.

PMID- 8751663
TI  - Merkel cell carcinoma: CT findings in 12 patients.
AB  - OBJECTIVE: The purpose of this report is to determine CT imaging findings in
      patients with Merkel cell carcinoma. MATERIALS AND METHODS: Fifty-three CT scans
      in 12 patients with biopsy-proven Merkel cell carcinoma were retrospectively
      reviewed with regard to size, location, and attenuation of primary skin lesions
      and visceral and lymph node metastases. Findings that were present in 12 patients
      form the basis of this report. RESULTS: Primary skin lesions were manifested on
      CT scans in four patients as cutaneous nodules that were hyper- or isodense in
      relation to muscle. Sites of metastases included regional lymph nodes (n = 6),
      distant lymph nodes (n = 11), the liver (n = 3), and subcutaneous fat (n = 4). We
      also found metastases in the mediastinum, the peritoneum, the adrenal gland, and
      the lung. Usually nodal and subcutaneous metastases were slightly hyperdense.
      Subcutaneous linear stranding was associated with the lesions. CONCLUSION: CT is
      useful in the staging of Merkel cell carcinoma.

PMID- 8751664
TI  - Polyhedral microcalcifications on mammograms: prevalence and morphometric
      analysis.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence and the
      mammographic appearance of polyhedral microcalcifications. MATERIALS AND METHODS:
      Prospectively, we evaluated screening mammograms in 2000 women for polyhedral
      microcalcifications. The number of polyhedral microcalcifications on routine and
      magnification views was established, and a quantitative analysis was done to
      determine if the shape of the polyhedral microcalcifications varied in the
      different projections. The ratio between the longer axis (R) and the shorter axis
      (r) was calculated. RESULTS: Two radiologists detected at least two polyhedral
      microcalcifications on one projection in 58 (3%) women. The number of polyhedral
      microcalcifications detected ranged from 2 to 47 (mean, 8.2) for screening
      mammograms and from 2 to 62 (mean, 13.4) on magnification views. Polyhedral
      microcalcifications were bilateral in 22 cases, scattered in one breast in 19
      cases, segmental in 10 cases, and grouped in a cluster in seven cases. Lateral
      projections showed more rhombohedral microcalcifications, and craniocaudal
      projections showed more square microcalcifications. CONCLUSION: The frequency of
      polyhedral microcalcifications is 3%. The shape of polyhedral microcalcifications
      varies: craniocaudal views show them to be square and lateral views show them to
      be rhombohedral.

PMID- 8751665
TI  - Pseudoaneurysm of the breast.

PMID- 8751666
TI  - Calcifications in axillary lymph nodes caused by fat necrosis.

PMID- 8751667
TI  - Prevalence of pathologically proven intrapulmonary lymph nodes and their
      appearance on CT.
AB  - OBJECTIVE: The objective of this study was to assess the prevalence of
      pathologically proven intrapulmonary lymph nodes and to evaluate their appearance
      on CT. MATERIALS AND METHODS: Over a 15-year period (1980-1994), 184 patients
      underwent minithoracotomies for evaluation of CT-detected peripheral pulmonary
      abnormalities. Of these 184 patients, 96 had well-circumscribed peripheral
      pulmonary nodules. The size, position, and radiographic features of all
      pathologically proven intrapulmonary lymph nodes were independently assessed by
      two experienced radiologists. RESULTS: The nodules in 17 (18%) of the 96 patients
      with well-circumscribed peripheral pulmonary nodules were pathologically proven
      to be intrapulmonary lymph nodes. Two of the 17 patients had two nodules; the
      remaining patients had solitary nodules. The maximum diameter of the nodules
      varied from 7 to 12 mm. All the nodes were located within 20 mm of a visceral
      pleural surface. Twelve of the nodules were located in the lower lobes, and the
      remaining nodules were located in the right middle lobe. CONCLUSION: Although
      intrapulmonary lymph nodes are not a well-known entity, our results indicate that
      they are discovered in a significant number of patients who undergo
      minithoracotomies for the evaluation of CT-detected pulmonary nodules. Although
      these lymph nodes do not possess any specific CT appearance, they should be
      considered in the differential diagnosis of single (or multiple) parenchymal
      nodules, particularly those found in the lower lobes.

PMID- 8751668
TI  - Thin-section CT findings of the lungs: experimentally induced bronchial and
      pulmonary artery obstruction in pigs.
AB  - OBJECTIVE: The purpose of this study was to investigate whether a mosaic pattern
      of lung attenuation, or lobular low attenuation, is revealed on CT imaging after
      induction of bronchial and pulmonary artery obstruction in pigs. MATERIALS AND
      METHODS: Eight anesthetized and ventilated pigs, four for bronchial obstruction
      and four for pulmonary artery obstruction, were examined with thin-section CT.
      Bronchial obstruction was induced at the subsegmental level using 2- to 3-mm
      radiopaque silicon spheres at 14 sites. Pulmonary artery obstruction was induced
      at 11 sites by dislodging 2- to 3-mm silicon spheres at the level of the superior
      vena cava. CT scans were obtained at end expiration immediately after the
      obstruction in all pigs (n = 8) and after 1 day (n = 3), 3 days (n = 5), 7 days
      (n = 4), 14 days (n = 4), and 28 days (n = 3). RESULTS: Of the 14 sites of
      bronchial obstruction, six sites (43%) on the immediate scans showed a lobular
      distribution of low attenuation distal to the spheres, which changed to
      atelectasis, consolidation, or normal on follow-up CT. Of the four sites that did
      not show changes in lung attenuation on immediate CT scans, two sites showed
      lobular low attenuation after 1 day. The mean attenuation value +/- SD for the
      lobular low attenuation was -737 H +/- 122 and that of the adjacent lung was -522
      H +/- 53 (p = .0077). None of the pulmonary artery obstruction sites showed
      visible change in lung attenuation, and mean attenuation values for obstructed
      sites and unobstructed sites did not show significant differences when scanned as
      many as 28 days after the immediate scans. CONCLUSION: Lobular low attenuation on
      thin-section CT was induced by bronchial obstruction, but we found no change in
      lung attenuation due to obstruction of the pulmonary arteries as many as 28 days
      after the immediate scans.

PMID- 8751669
TI  - Diagnosis of diaphragmatic trauma with helical CT in a swine model.
AB  - OBJECTIVE: The purpose of this study was to determine whether diaphragmatic
      injury can be accurately diagnosed with helical CT in a swine model. The
      hypothesis of our study was that thin-section helical CT with sagittal and
      coronal reformations can reliably detect injury of the diaphragm. MATERIALS AND
      METHODS: The study was performed in a swine model because of the similarity of
      the swine thorax to the human thorax. Ten swine had a limited abdominal helical
      CT (enteral contrast; 3-mm collimation; pitch, 1) before and after surgical
      creation of a 6-cm posterolateral laceration in the left hemidiaphragm. A repeat
      scan was obtained after 5 cm of gastric fundus was sutured through the
      laceration. The gastric fundus was used because it is the most commonly herniated
      viscus in human diaphragmatic injury. No IV contrast was used. Control,
      laceration, and herniation scans were reconstructed with 1.0-mm overlap and
      reformated in axial, sagittal, and coronal planes. Three observers scored each
      reformation as control or injury (defined as laceration or herniation) in a
      blinded and randomized fashion. RESULTS: Using helical CT, the observers were
      able to distinguish diaphragmatic injury from controls (p < .0001). The
      sensitivity and specificity were 92% and 87%, respectively, for sagittal
      reformations; 85% and 87%, respectively, for coronal reformations; and 73% and
      80%, respectively, for axial reformations. Sagittal reformations proved superior
      to coronal or axial reformations (p = .01). The results were independent of
      individual observers: We found no significant difference in accuracy among the
      three observers. CONCLUSION: Helical CT can accurately detect diaphragmatic
      injury in a swine model.

PMID- 8751671
TI  - Pulmonary arteriovenous malformation.

PMID- 8751670
TI  - Intracavitary urokinase therapy as an adjunct to percutaneous drainage in a
      patient with a multiloculated empyema.

PMID- 8751673
TI  - Pulmonary perfusion and angiography: evaluation with breath-hold enhanced three
      dimensional fast imaging steady-state precession MR imaging with short TR and TE.

PMID- 8751672
TI  - Transcatheter instillation of urokinase into loculated pleural effusion: analysis
      of treatment effect.
AB  - OBJECTIVE: Our objective was to evaluate the usefulness of intracavitary
      instillation of urokinase in the treatment of loculated pleural effusion.
      SUBJECTS AND METHODS: We analyzed CT and sonographic scans of 31 patients with
      loculated pleural effusion treated with intracavitary urokinase. When the
      drainage was less than 100 ml/day, urokinase was instilled through the catheter
      until the drainage was less than 50 ml/day. Response to the treatment was
      assessed on follow-up chest radiographs and classified into three groups:
      completely effective (lung expansion > 80%), partially effective (20-80%), and
      ineffective (< 20%). The sonographic pattern of pleural fluid was classified as
      anechoic, linear septated, or honeycomb, and the thickness of the parietal pleura
      was measured on CT scans. RESULTS: Of the 16 patients in whom treatment was
      completely effective, sonography showed an anechoic appearance in 12 and a linear
      septated appearance in four, and the thickness of the parietal pleura on CT scans
      was 2 mm in six, 3 mm in seven, and 4 mm in three. Of the nine patients in whom
      treatment was partially effective, sonography showed an anechoic appearance in
      six and a linear septated appearance in three, and the thickness of the parietal
      pleura on CT scans was 3 mm in five and 4 mm in four. Of the six patients in whom
      treatment was ineffective, sonography showed a linear septated appearance in one
      and a honeycomb appearance in five, and the thickness of the parietal pleura on
      CT scans was 3 mm in one, 4 mm in two, 5 mm in one, and 6 mm in two. CONCLUSION:
      Urokinase instillation through a percutaneous catheter was effective in the
      treatment of loculated pleural effusion in most patients but was not effective in
      patients whose pleural fluid had a honeycomb appearance on sonography or whose
      parietal pleura had a thickness of more than 5 mm on CT scans.

PMID- 8751674
TI  - Endovascular catheter biopsy of a pulmonary artery sarcoma.

PMID- 8751675
TI  - Side-exiting coaxial needle for aspiration biopsy.

PMID- 8751676
TI  - A comparison of the Gallini IBI and TSK Surecut biopsy needles.

PMID- 8751677
TI  - Pulseless foot after stab wound to the calf: clue to a therapeutically important
      arterial variant.

PMID- 8751678
TI  - CT-guided drainage of multilocular pelvic and gluteal tuberculous abscesses.

PMID- 8751679
TI  - Intraarticular foot and ankle injections to identify source of pain before
      arthrodesis.
AB  - OBJECTIVE: The purpose of our study was to evaluate the usefulness of diagnostic
      joint injections in patients with foot and ankle pain when the radiologist
      attempts to identify the source of pain. This study also correlated the results
      of injection with outcome after arthrodesis. MATERIAL AND METHODS: We
      retrospectively reviewed the records of 22 patients who had a foot or ankle joint
      injected to identify a source of pain and who later underwent arthrodesis of the
      painful joint. All patients had long-term foot and ankle symptoms of variable
      causes. Twenty-four joints were assessed: 13 subtalar, five talonavicular, four
      ankle, one calcaneocuboid, and one metatarsocuneiform. All patients had plain
      radiographs, 11 had CT studies, and five had bone scans. Contrast material was
      used to assess adequate positioning of the needle inside the joint before
      injection. All joints were injected under fluoroscopic control. Steroid was added
      in eight joints. After injection, patients were assessed for relief of symptoms.
      Patients subsequently underwent arthrodesis on the basis of the results of the
      injection. RESULTS: In 20 patients (22 joints), long-term follow-up showed that
      injections allowed us to correctly identify the source of pain and successfully
      guide arthrodesis. Of these 20 patients, 17 had significant pain relief after
      injection and fusion, whereas three patients had mild or no response. With one of
      these patients, we injected other joints and changed surgical plans. One of the
      two remaining patients had more pain relief after injection than after
      arthrodesis. The other patient had no relief after injection, but subsequent
      fusion because of persistent pain was successful. We found imaging studies to be
      less useful than diagnostic injections when we were attempting to identify the
      source of pain. CONCLUSION: Intraarticular injection of anesthetic in painful
      foot and ankle joints helped us confirm the source of pain in 20 of 22 patients,
      which in turn led to successful arthrodesis and good outcomes for these patients.

PMID- 8751680
TI  - MR imaging of posterior tibial tendon dysfunction.
AB  - OBJECTIVE: The purpose of this study was to describe the MR findings of posterior
      tibial tendon dysfunction. MATERIALS AND METHODS: MR images and medical records
      were reviewed for 11 patients with surgically proven posterior tibial tendon
      abnormalities (i.e., tears or tenosynovitis) and for six patients with clinical
      evidence of posterior tibial tendon dysfunction. Our study group included 16
      women and one man from 37 to 70 years old (mean, 53.5 years old). MR examinations
      used T1-weighted and T2-weighted spin-echo sequences in the oblique axial and
      sagittal planes. RESULTS: Abnormal MR findings were observed in all 17 patients.
      The spectrum of MR abnormalities included fluid in the tendon sheath of a normal
      tendon interpreted as isolated paratenonitis (tenosynovitis, n = 3); tendon
      thickening and surrounding fluid with normal tendon signal interpreted as
      tendinosis (degeneration, n = 1); tendon thickening with increased linear or
      heterogeneous intrasubstance signal interpreted as partial tear (n = 11); tendon
      discontinuity with fluid-filled tendon sheath interpreted as complete rupture (n
      = 2). In 11 patients, the posterior tibial tendon was explored at surgery. In
      these patients, MR imaging accurately showed two cases of isolated paratenonitis,
      one case of tendinosis, four partial tears, and two complete ruptures. In the
      remaining two patients, the presumed MR diagnosis did not correlate very closely
      with the surgical findings: one patient with isolated paratenonitis shown by MR
      imaging had tendinosis found at surgery; however, the surgery in this patient
      followed the MR examination by 10 months, a time during which degeneration might
      have occurred. The other patient had an MR diagnosis of partial tear, which was
      not found at surgery; however, tendon degeneration was severe and a small tear
      not reaching the tendon surface could have been missed at inspection. MR imaging
      characteristics of severe tendinosis and partial tear may overlap. CONCLUSION: MR
      imaging is effective for detecting abnormalities related to posterior tibial
      tendon dysfunction. Familiarity with the appearance of these changes facilitates
      accurate characterization.

PMID- 8751681
TI  - Elastofibroma dorsi: radiologic findings in 12 patients.
AB  - OBJECTIVE: We report radiologic findings in 12 patients with elastofibroma dorsi
      to heighten radiologist awareness of the imaging characteristics of these benign,
      often asymptomatic lesions. Because these lesions can usually be diagnosed on the
      basis of their imaging characteristics, increased awareness of these
      characteristics will decrease misdiagnosis of these lesions as malignancies and
      avoid unnecessary biopsies and surgeries. MATERIALS AND METHODS: We
      retrospectively reviewed the radiology and pathology of nine patients with
      surgically excised elastofibromas and the radiology of three patients with
      radiologically diagnosed elastofibromas. RESULTS: Twenty-one elastofibromas were
      imaged in 12 patients. Female-to-male ratio was 5:1; mean age was 65 years old.
      Of the nine patients in whom both sides of the chest wall were imaged, all (100%)
      had bilateral elastofibromas. Nineteen elastofibromas (90%) had the typical CT
      and MR appearances described in the literature: a poorly circumscribed,
      heterogeneous soft-tissue mass, with tissue of attenuation or signal intensity
      similar to that of skeletal muscle interlaced with strands of fat. One
      elastofibroma imaged twice over a 4-year period showed interval growth. All
      elastofibromas were sub- or infrascapular or in both locations. Of the 21
      elastofibromas imaged, only four were perceived by the initial interpreting
      radiologist, and of these, only one was correctly diagnosed. CONCLUSION: Our
      study shows that many radiologists may not be aware of the diagnosis of
      elastofibroma, as few of the cases in our series were perceived or correctly
      diagnosed by the interpreting radiologist. Our cases show many of the classic
      findings of elastofibromas described in the literature. In addition, our series
      shows that elastofibromas are commonly bilateral, a feature that has not been
      strongly emphasized in the literature but one that is helpful in making the
      radiologic diagnosis. The finding of a similar contralateral lesion, when
      present, virtually eliminates malignancy from the differential diagnosis and
      further supports the presumptive diagnosis of elastofibromas. Increased awareness
      of the characteristic appearance and location of these benign, often asymptomatic
      lesions will increase radiologic diagnosis, decrease the need for biopsy, and
      decrease surgical removal of elastofibromas as presumed malignancies.

PMID- 8751682
TI  - Ribbing disease (multiple diaphyseal sclerosis): imaging and differential
      diagnosis.
AB  - OBJECTIVE: This study describes the clinical presentation and the course of
      Ribbing disease in six patients and illustrates imaging features on plain
      radiography, conventional and computed tomography, and 99mTc-methylene
      diphosphonate bone scans. MATERIALS AND METHODS: Between 1982 and 1990, six
      female patients presented with painful bony lesions that were believed to be
      Ribbing disease. Ten bones were affected: both tibiae in three patients, a
      unilateral tibia in one, both femora in one, and a unilateral femur in one. Plain
      radiographs and either conventional or computed tomography were available for all
      patients and 99mTc-methylene diphosphonate bone scans, for five patients. All
      patients underwent open biopsy and/or surgical decompression. RESULTS: The
      diagnosis was reached in all patients through a combination of clinical findings
      (lack of systemic signs of infection or laboratory values suggesting metabolic
      bone disease), imaging, histologic evaluation, and specimen cultures. Radiographs
      and tomographic studies showed benign-appearing endosteal and periosteal cortical
      thickening. Intense uptake of radionuclide tracer was confined to the shaft of
      all involved bones. All pathologic specimens revealed nonspecific changes that
      included a slow increase in the mass of cortical and endosteal bone. These
      specimens also assisted in excluding neoplastic or infectious causes for the new
      bone formation. CONCLUSION: Ribbing disease is a rare disorder that, on imaging
      studies, may simulate stress fracture, chronic infection, bone-forming neoplasia,
      or a systemic metabolic or endocrine disorder. Clinical and imaging features may
      suggest the correct diagnosis.

PMID- 8751683
TI  - Axillary nerve injury after anterior glenohumeral dislocation: MR findings in
      three patients.
AB  - OBJECTIVE: We performed this study to demonstrate the MR imaging findings that
      indicate an anterior dislocation has caused an axillary nerve injury. CONCLUSION:
      MR images of the shoulder can show findings indicating that an axillary nerve
      injury has been caused by an anterior shoulder dislocation. All MR examinations
      should be evaluated for these findings, particularly if the patient has a history
      of anterior shoulder dislocation.

PMID- 8751684
TI  - Subtle fractures about the knee: innocuous-appearing yet indicative of
      significant internal derangement.

PMID- 8751685
TI  - Complications after anterior cruciate ligament reconstruction: radiographic and
      MR findings.

PMID- 8751686
TI  - Infected aortic aneurysm and vertebral osteomyelitis after intravesical bacillus
      Calmette-Guerin therapy.

PMID- 8751687
TI  - Esophageal occlusion caused by thoracic spine fracture or dislocation: CT
      diagnosis.

PMID- 8751688
TI  - Mastocytosis of the axial skeleton presenting as an epidural mass lesion: MR
      imaging appearance.

PMID- 8751689
TI  - Functional abnormalities of the esophagus: a prospective analysis of radiographic
      findings relative to age and symptoms.
AB  - OBJECTIVE: The prevalence and severity of functional abnormalities of the
      esophagus seen on fluoroscopic examination were compared with the age and
      symptoms of the patients. SUBJECTS AND METHODS: The esophagus was examined
      radiographically in 139 consecutive outpatients 19-84 years old. All patients
      completed a data sheet about their symptoms, and medical records were reviewed to
      determine the main indication for the examination. Videofluoroscopy was used to
      evaluate primary peristalsis, proximal escape, and tertiary activity in the
      esophagus. The severity of proximal escape and activity was classified. RESULTS:
      Patients were categorized into three age groups: 39 years old or younger (n =
      33); from 40 to 60 years old (n = 55); and 61 years old or older (n = 51).
      Abnormal esophageal motility, defined as disruption of peristalsis on two or more
      of five swallows, was found in 24% of patients 39 years old or younger, 36% of
      patients from 40 to 60 years old, and in 49% of patients 61 years old or older (p
      > .05). However, evaluation of the number of disrupted peristaltic swallows by
      age revealed 18% abnormal swallows in patients 39 years old or older, 27% in
      patients from 40 to 60 years old, and 37% in patients 61 years old or older (p <
      .01). Proximal escape and tertiary contractions increased significantly with the
      age of the patient. Regardless of age, proximal escape was seen in 79% of
      swallows and tertiary contractions were seen in 48% of swallows with disrupted
      peristalsis. The prevalence and severity of proximal escape and tertiary
      contractions increased in the older patients. Symptoms had no correlation with
      status of esophageal motility (p > .05). In 22 patients with secondary diseases,
      including rheumatoid arthritis and diabetes mellitus, those diseases showed no
      correlation with the status of esophageal motility. CONCLUSION: The prevalence of
      functional abnormalities of the esophagus increased with age. Most patients with
      abnormal swallows showed proximal escape with or without tertiary activity.
      Patients' symptoms and other diseases did not correlate with the status of their
      esophageal motility.

PMID- 8751690
TI  - Comparison of tailored and empiric scan delays for CT angiography of the abdomen.
AB  - OBJECTIVE: Scan delays for CT angiography of the abdomen are currently
      individualized by matching a scan delay to the transit time of a test bolus of IV
      contrast material to the abdominal aorta. We sought to determine whether this
      procedure improves the extent and uniformity of aortic enhancement when compared
      with the use of a standard scan delay that is determined empirically. SUBJECTS
      AND METHODS: CT angiography of the upper abdomen (either the entire abdominal
      aorta or the aorta spanning the length of both kidneys for dedicated renal
      studies) was obtained in 48 patients who were considered to have normal cardiac
      function as determined by their referring physicians. Patients were randomized to
      undergo CT angiography that used either a standard scan delay of 20 or 22 sec
      (group 1, n = 26) or a tailored scan delay (group 2, n = 22), all other imaging
      parameters being identical. Tailored delays were determined by measuring contrast
      transit time to the abdominal aorta with software from the SmartPrep system. For
      each patient, aortic attenuation was measured at three different anatomic levels,
      and a lower threshold of 160 H was considered optimal. The number of attenuation
      values above this threshold, the mean attenuation, and the attenuation changes
      for each unit length along the abdominal aorta were then compared for the two
      groups of patients. RESULTS: Fifty-eight (74%) of 78 aortic attenuation values in
      group 1 and 55 (88%) of 69 in group 2 were above 160 H. Mean attenuation values
      were 192.2 H +/- 8.1 (+/-SE) in group 1 and 199.2 H +/- 10.1 in group 2. These
      values and the attenuation changes for each unit length along the abdominal aorta
      3.7 H/cm +/- 1.7 for group 1 and 2.2 H/cm +/- 2.0 for group 2- were not
      significantly different. CONCLUSION: Tailoring the scan delay for CT angiography
      of the abdomen in patients considered to have normal cardiac function requires
      additional IV contrast agent, time, and patient imaging and does not improve the
      extent or uniformity of aortic enhancement over that obtained with a standard,
      empiric scan delay.

PMID- 8751691
TI  - CT evaluation of infradiaphragmatic air in patients treated with mechanically
      assisted ventilation: a potential source of error.
AB  - OBJECTIVE: The purpose of this study was to describe the CT features of
      infradiaphragmatic air that may develop in patients after mechanically assisted
      ventilation, its location, its pathway of transdiaphragmatic dissection, and its
      extension into the abdomen. MATERIALS AND METHODS: We retrospectively evaluated
      six consecutive adult patients with pneumomediastinum associated with positive
      end-expiratory pressure therapy who developed intraabdominal air and were imaged
      with CT in our institution-between 1993 and 1995. Abdominal CT examinations were
      reviewed and correlated with the clinical findings, follow-up examinations, and
      exploratory laparotomies in four patients. RESULTS: In four patients, air present
      in the anterior mediastinum (endothoracic fascia) was seen to extend into the
      anterior abdominal wall within the extraperitoneal space. In a fifth patient, the
      air was located extraperitoneally and intraperitoneally. In the remaining
      patient, air was present exclusively in the peritoneal cavity. In only two
      patients did we detect small amounts of air in the posterior retroperitoneum. In
      five patients, we also detected subcutaneous emphysema and/or air dissection into
      the muscle planes of the anterolateral abdominal wall. CONCLUSION: In patients on
      mechanically assisted ventilation, anterior mediastinal air can dissect through
      the diaphragm into the anterior abdominal extraperitoneal space. This anterior
      pathway of infradiaphragmatic extension of air can be erroneously diagnosed as
      intraperitoneal air, which may lead to unnecessary exploratory laparotomies.
      Also, anterior mediastinal air can enter the peritoneal cavity, particularly in
      patients with a history of median sternotomy.

PMID- 8751692
TI  - Dynamic contrast-enhanced MR imaging of perianal fistulas.
AB  - OBJECTIVE: The objective of this study was to prospectively compare dynamic
      contrast-enhanced MR imaging with MR sequences previously described for assessing
      perianal fistulas in order to determine the best MR protocol for their
      evaluation. SUBJECTS AND METHODS: MR examinations of 42 consecutive patients with
      clinically suspected perianal fistulas were independently evaluated by two
      experienced observers blinded to the findings of digital rectal examination. The
      observers' evaluations occurred before definitive surgical exploration. All
      patients had body-coil MR imaging examinations, including the following sequences
      that were ranked for anatomic and pathologic information: spin-echo T1-weighted,
      short inversion time inversion recovery, and dynamic contrast-enhanced MR imaging
      in the coronal plane; and spin-echo T2-weighted imaging in the axial plane.
      Surgical findings were accepted as the gold standard and were recorded
      independently by the surgeon, who was unaware of the findings of the MR
      assessment. MR findings were subsequently correlated with digital rectal
      examination before surgery and with clinical follow-up. RESULTS: MR imaging
      correctly allowed our blinded observers to predict the surgical anatomy of
      perianal disease in 37 of the 42 patients (accuracy, 88%). For detection of the
      presence and site of an enteric fistulous entry, MR imaging had a sensitivity of
      97%, a specificity of 67%, a positive predictive value of 88%, and a negative
      predictive value of 89%. On MR imaging examination, eight patients had no
      fistula, 12 had simple intersphincteric fistulas, and 22 had complex fistulas. MR
      imaging revealed all 14 perianal abscesses and fluid collections found at
      surgery. Digital rectal examination before surgery failed to reveal abscesses or
      important secondary tracks in eight of the 22 complex fistulas. For anatomic and
      pathologic depiction of fistulas, dynamic contrast-enhanced MR imaging ranked as
      the best sequence for 22 of 34 fistulas. The short inversion time inversion
      recovery sequence, which was unable to distinguish small abscesses from perianal
      inflammation and showed spurious high signal in old fibrotic tracks, led our
      observers to misdiagnose five cases. In four patients for which initial surgery
      did not confirm enteric entry sites that our observers had predicted by MR
      imaging, follow-up has confirmed the observers' diagnoses. The observers'
      evaluations of the MR examinations agreed in 37 (88%) of the 42 cases.
      CONCLUSION: MR imaging is more accurate than digital rectal examination before
      surgery in detecting complex features of perianal fistulas. MR imaging is
      noninvasive, is highly accurate, and has low interobserver variability. With MR
      imaging, observers may better predict outcome than with initial surgical
      exploration. MR assessment that includes dynamic contrast-enhanced MR imaging and
      axial T2-weighted sequences (examination time, 20 min) provides the anatomic and
      pathologic information required to guide surgical management.

PMID- 8751693
TI  - CT differentiation of tuberculous peritonitis and peritoneal carcinomatosis.
AB  - OBJECTIVE: The purpose of this study was to determine the potential of CT for
      distinguishing tuberculous peritonitis from peritoneal carcinomatosis in 135
      clinically or pathologically proven cases. MATERIALS AND METHODS: Abdominal CT
      scans in 135 patients of tuberculous peritonitis (n = 42) and peritoneal
      carcinomatosis (n = 93) with documented omental, mesenteric, or peritoneal
      pathology were retrospectively reviewed. CT findings were evaluated in each group
      of patients for the morphologic appearance of mesenteric or omental abnormalities
      as well as for visualization of the spleen and liver, the lymph nodes, and
      ascites. Statistical comparisons using multivariate logistic regression analysis
      were performed to adjust for the differences in CT findings between the two
      groups. RESULTS: Mesenteric changes were more commonly seen in patients with
      tuberculous peritonitis (98%) than in patients with peritoneal carcinomatosis
      (70%) (p < .01). Micronodules (less than 5 mm in diameter) were noted in
      approximately one half of patients with tuberculous peritonitis or peritoneal
      carcinomatosis, but macronodules (> or = 5 mm in diameter) were much more
      frequently seen in patients with tuberculous peritonitis (52%) than in patients
      with peritoneal carcinomatosis (12%) (p < .01). The omentum appeared to be more
      irregularly infiltrated in peritoneal carcinomatosis patients (p < .01). The thin
      omental line covering the infiltrated omentum was seen in 13 patients with
      tuberculous peritonitis but in only four patients with peritoneal carcinomatosis
      (p < .01). In peritoneal or extraperitoneal masses in patients with tuberculous
      peritonitis, a low-density center was seen in 18 cases (43%) and calcification
      was noted in six cases (14%). The prevalences of splenomegaly and splenic
      calcification were higher in patients with tuberculous peritonitis. Using
      multivariate analysis, we calculated the sensitivity of CT for predicting
      tuberculous peritonitis and peritoneal carcinomatosis as 69% and 91%,
      respectively. CONCLUSION: Although most CT findings that we analyzed overlap
      these diseases, using a combination of CT findings increased our ability to
      distinguish tuberculous peritonitis from peritoneal carcinomatosis.

PMID- 8751694
TI  - Saline MR peritoneography.
AB  - OBJECTIVE: Our objective was to describe a new method for the evaluation of
      peritoneal surfaces in patients with intraperitoneal carcinomatosis and
      sarcomatosis. CONCLUSION: Fast spin-echo T2-weighted imaging in conjuction with
      intraperitoneally instilled saline permits detailed evaluation of peritoneal
      surfaces, omentum, and mesenteries. The detection of tumor implants is
      facilitated by their visualization against the saline background. Additionally,
      normal and abnormal saline distribution patterns can be identified. This
      technique may also be useful in predicting response to intraperitoneally
      instilled chemotherapy.

PMID- 8751695
TI  - Multiple-phase helical CT of the liver for detecting small hepatomas in patients
      with liver cirrhosis: contrast-injection protocol and optimal timing.
AB  - OBJECTIVE: Helical CT scanners allow multiple-phase sequential scans of the
      entire liver to be obtained during a single bolus injection of contrast material.
      The purpose of this study was to compare two injection protocols and to establish
      timing that would optimize detection of hepatomas less than 3 cm in diameter.
      SUBJECTS AND METHODS: Triple-phase helical CT of the liver was evaluated in 217
      patients who had liver cirrhosis and were referred for known or suspected
      hepatomas. Proof of individual neoplasms was based on biopsy results, surgical
      findings, or findings of other imaging studies. Sixty percent nonionic contrast
      material, infused at 2 or 4 ml/sec, was followed by sequential arterial-phase,
      portal-venous phase, and equilibrium-phase helical scans of the liver. Aortic and
      hepatic enhancement curves were constructed by measuring CT attenuation. The CT
      attenuation values of individual tumor lesions were also measured. We compared
      the degree of enhancement of normal structures and tumors obtained with four scan
      protocols (injection at 2 ml/sec with a 30-sec scan delay [n = 54], injection at
      2 ml/sec with a 35-sec scan delay [n = 47], injection at 4 ml/sec with a 20-sec
      scan delay [n = 56], and injection at 4 ml/sec with a 25-sec scan delay [n = 60]
      and determined the optimal injection protocol and timing for CT acquisition.
      RESULTS: Peak aortic and hepatic enhancement was obtained earlier with the 4
      ml/sec protocol (at 24 sec and 61 sec versus 36 sec and 90 sec for the 2-ml/sec
      protocol). The peak attenuation value of the aorta was higher with the 4-ml/sec
      protocol (330 H versus 186 H for the 2-ml/sec protocol). However, peak hepatic
      attenuation was similar for both protocols (98 H for the 4-ml/sec protocol versus
      92 H for the 2-ml/sec protocol). Liver-tumor contrast was highest in the arterial
      phase with both protocols. The next highest contrast was obtained during the
      equilibrium phase. Liver-tumor contrast in the portal-venous phase was
      significantly lower than that in the other two phases. Tumor enhancement was
      significantly higher in scans obtained using the 4-ml/sec protocol with a delay
      time of 25 sec than those obtained with a delay time of 20 sec. In 109 hepatomas,
      35 tumors were only seen or were most conspicuous during the arterial phase, four
      tumors were most conspicuous during the equilibrium phase, and one tumor was most
      conspicuous during the portal-venous phase. CONCLUSION: Arterial-phase helical CT
      of the liver after 4-ml/sec injection of contrast material significantly improves
      detection of hepatomas less than 3 cm in diameter when performed in addition to
      delayed scanning. Portal-venous phase helical CT is of limited value in detecting
      small hepatomas.

PMID- 8751696
TI  - Percutaneous RF interstitial thermal ablation in the treatment of hepatic cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate the usefulness of RF
      interstitial thermal ablation for treating hepatic cancer. SUBJECTS AND METHODS:
      Fifty patients, 39 who had 41 hepatocellular carcinoma nodules and 11 who had 13
      hepatic metastatic nodules, underwent RF interstitial thermal ablation. In all
      but one, a thermal necrosis volume greater than the tumoral nodule volume was
      created to obtain total tumor destruction. One large tumor was treated for
      debulking purposes. RESULTS: Hepatocellular carcinoma nodule destruction was
      achieved in a mean of 3.3 sessions of RF interstitial thermal ablation. During a
      mean follow-up of 22.6 months (range, 3-66 months), 16 (41%) of 39 patients had
      recurrences; two (5%) of these patients showed local recurrences and the
      remaining 14 (36%) had new lesions. Nine of these 16 patients underwent further
      RF interstitial thermal ablation that proved effective. RF interstitial thermal
      ablation was also successfully repeated in four patients who had a second
      recurrence. With RF interstitial thermal ablation, we treated 54 hepatocellular
      carcinoma nodules in 39 patients. Eleven (28%) of the 39 patients died: five from
      hepatic failure due to advanced cancer and six from causes other than cancer.
      Autopsy was performed on three patients who died from causes other than cancer,
      one had had two new courses of RF interstitial thermal ablation for two new
      lesions. Gross examination failed to detect two treated tumor nodules; histologic
      examination of three other treated tumor nodules showed total necrosis in two
      nodules and a 3-mm focus of viable cancer cells in the other nodule. Cumulative
      survival curves showed the median survival time to be 44 months. The survival
      rate for the first year was 0.94, 0.86 for the second year, 0.68 for the third
      year, and 0.40 for the fourth and fifth years. In the patients treated for
      metastatic nodules, posttreatment imaging studies showed necrosis that varied
      from 80% to 100% in all cases. Pathologic studies performed on two patients who
      underwent surgery after RF interstitial thermal ablation showed 100% necrosis in
      one case and 80% necrosis in the other. CONCLUSION: RF interstitial thermal
      ablation is a useful percutaneous treatment for hepatic cancer.

PMID- 8751697
TI  - Segmental hepatic necrosis after blunt abdominal trauma: CT findings.

PMID- 8751698
TI  - Helical CT of renal masses: the value of delayed scans.
AB  - OBJECTIVE: Routine scanning techniques used for helical CT of the abdomen result
      in dense cortical opacification of the kidney, whereas the medulla and collecting
      system are not well opacified, which potentially compromises detection of renal
      masses. The purpose of this retrospective study was to determine if additional
      delayed views (taken approximately 2-4 min after the start of injection of
      contrast material) are necessary for the detection and characterization of renal
      masses. MATERIALS AND METHODS: Early (60-70 sec after the start of the injection
      of contrast material) and delayed scans of 40 patients with suspected renal
      masses were blindly evaluated by two observers. The patients harbored a total of
      187 renal masses (including 62 solid masses). Each region of the kidney (upper,
      middle, and lower pole) was scored for the presence of a mass. Scoring was done
      as a binary decision and also as a five-point confidence score for receiver
      operating characteristic analysis. RESULTS: We found 97 regions that contained
      renal masses and 114 regions that did not. Receiver operating characteristic
      analysis revealed the observers to have significantly greater confidence in
      detection of renal masses on the delayed scans. The binary data showed the two
      observers to have a sensitivity of 97% for delayed scans versus 77% (p = .0002)
      and 89% (p = .027), respectively, for the early scans. For the first observer,
      early and delayed scans were of equal specificity, but for the second observer,
      the delayed scans yielded greater specificity (94% versus 85%, p = .024). On the
      early scans, both observers were significantly more likely to miss a neoplastic
      lesion than a nonneoplastic lesion. The less experienced of the two observers
      also tended to have greater difficulty in characterizing the lesions on the early
      scans. CONCLUSION: Because of the significant risk of missing a renal mass,
      especially a neoplasm, on early cortical-phase scans, additional delayed scans
      appear justified when a renal mass is suspected on the basis of other imaging
      tests or clinical history.

PMID- 8751699
TI  - Traumatic occlusion of the renal artery: helical CT diagnosis.
AB  - OBJECTIVE: Eight patients with traumatic occlusion of the renal artery were
      retrospectively reviewed to assess the diagnostic contribution of helical CT and
      to determine whether the information it provides can replace angiographic data in
      patient evaluations. MATERIALS AND METHODS: We reviewed the medical records and
      imaging studies of eight patients with renal artery occlusion caused by blunt
      abdominal trauma. All patients were scanned using a helical protocol that
      included an 8-mm collimation with a 1:1 pitch and a monophasic IV injection of
      iodinated contrast material. The timing of the imaging studies, the type of
      surgical treatment, and the patient outcome were tabulated. Evaluated data
      included the location of the occlusion as depicted by helical CT and angiography,
      whether a CT nephrogram was obtained, the presence of a peripheral rim effect,
      and the nature of associated injuries. RESULTS: Helical CT revealed occlusion of
      a main renal artery in seven patients and obstruction of a main branch in one
      patient. In all cases the occlusion occurred within the proximal 2 cm of the
      renal artery. In five patients, the findings were depicted equally well by
      helical CT and angiography. In two patients, the helical CT findings were
      confirmed by surgery and autopsy, respectively. Significant associated injuries
      were revealed in seven patients. The CT nephrogram was absent in seven patients
      and partially present in one patient. The peripheral rim effect was seen in six
      patients. CONCLUSION: Basic contrast-enhanced helical CT can reliably reveal
      traumatic occlusion of the renal artery and depict the level of obstruction.

PMID- 8751700
TI  - Aspiration and sclerotherapy of symptomatic simple renal cysts: value of two
      injections of a sclerosing agent.
AB  - OBJECTIVE: The purpose of our study was to determine whether two injections of
      sclerosant were more effective than a single injection in treating symptomatic
      simple renal cysts. SUBJECTS AND METHODS: We reviewed our results obtained by
      simple aspiration, by aspiration and a single sclerosant injection, and by
      aspiration followed by two injections of sclerosing agent over 48 hr. We used 95%
      alcohol because of its capacity to safely sclerose the epithelial lining of renal
      cyst walls without damaging the renal parenchyma. After 1-3 min of contact with
      the alcohol, the epithelial cells lining the cyst become fixed and nonviable; the
      cyst capsule is penetrated only after 4-12 hr. Longer contact of alcohol with the
      epithelial cell lining should theoretically result in the nonviability of more
      epithelial cells and therefore in a lower recurrence rate of cysts after
      aspiration and sclerotherapy. Our subjects were 46 patients, 30 men and 16 women,
      treated over a 13-year period. They ranged in age from 38 to 75 years old (mean
      age, 47 years). Fifty-two cysts were treated. Twenty patients (20 cysts) had
      simple aspiration only, 15 patients (19 cysts) had a single injection of
      sclerosant after aspiration, and 11 patients (13 cysts) had two sclerosant
      injections after aspiration. RESULTS: Of the 20 patients who had simple
      aspiration only, 16 cysts had recurred after 2 years. In the single-injection
      group of patients, we found six recurrences after 2 years. No recurrence has
      occurred in the group of patients who had two sclerosant injections after
      aspiration. CONCLUSION: Our findings suggest that the results of treating
      symptomatic simple renal cysts are better in terms of recurrence with two
      successive injections of 95% alcohol, probably because of the nonviability of
      more epithelial cells lining the cyst as a result of a longer period of contact
      with the alcohol. Our sonographic finding of pseudotumors at the sites of
      previously aspirated giant cysts in two patients is recorded.

PMID- 8751701
TI  - Conventional color Doppler velocity sonography versus color Doppler energy
      sonography for the diagnosis of acute experimental torsion of the spermatic cord.
AB  - OBJECTIVE: We compared color Doppler velocity sonography and color Doppler energy
      sonography for the diagnosis of spermatic cord torsion in a canine model and
      determined the degree of torsion necessary to acutely halt testicular blood flow.
      MATERIALS AND METHODS: Spermatic cord torsion was created in five dogs by
      exposing and rotating the ipsilateral testis 0 degree, 180 degrees, 270 degrees,
      360 degrees, 450 degrees, and 540 degrees. Detorsion followed. The testicles were
      scanned at each torsion stop using both color Doppler velocity sonography and
      color Doppler energy sonography. Doppler parameters were optimized (by phantom
      and test scans) and maintained at a tolerable noise level throughout the
      experiment. Readers who were unaware of the degree of torsion compared flow in
      the rotated and contralateral control testes. RESULTS: Flow became undetectable
      by color Doppler velocity sonography and color Doppler energy sonography at 450
      degrees in four of five cases and at 540 degrees in one of five cases. We found
      no significant difference between the velocity and the energy techniques for
      detecting this absence of flow (p > .05, Wilcoxon test). We found a significant
      difference in degree of flow for both techniques when comparing controls and all
      degrees of torsion combined (p < .006, Mann-Whitney test), but significance was
      achieved at lesser degrees of torsion with the velocity technique than with the
      energy technique (180 degrees and 360 degrees, respectively, Wilcoxon test).
      CONCLUSION: Color Doppler energy sonography was not significantly more sensitive
      than color Doppler velocity sonography for the diagnosis of spermatic cord
      torsion in this model. Complete occlusion of arterial inflow occurred at 450-540
      degrees of torsion.

PMID- 8751702
TI  - Endodermal sinus tumor of the ovary: imaging evaluation.
AB  - OBJECTIVE: Endodermal sinus tumor of the ovary is a rare complex malignant tumor
      that occurs in young women. We performed this study to determine the imaging
      characteristics of this tumor. CONCLUSION: Endodermal sinus tumor of the ovary
      presents as a large complex abdominal mass that can be predominantly cystic and
      should be considered in the differential diagnosis of complex abdominal masses in
      girls and young women. In addition, upon encountering a mass with these imaging
      characteristics in the proper clinical setting, serum alpha-fetoprotein levels
      should be measured to help make a presurgical diagnosis and to obtain a baseline
      value.

PMID- 8751703
TI  - Tumefactive extramedullary hematopoiesis of the kidney in a patient with
      idiopathic thrombocytopenic purpura.

PMID- 8751704
TI  - Vascular enhancement with superparamagnetic iron oxide.

PMID- 8751705
TI  - Condyloma acuminatum of the bladder.

PMID- 8751706
TI  - Underdiagnosis of parathyroid adenomas by sonography.

PMID- 8751707
TI  - Idiopathic spontaneous hemomediastinum and bilateral hemothorax.

PMID- 8751708
TI  - MR imaging of focal hepatic injury due to use of surgical retractors.

PMID- 8751709
TI  - Breast pseudoaneurysm after core biopsy.

PMID- 8751710
TI  - New approach in the diagnosis of and therapy for Hughes-Stovin syndrome.

PMID- 8751711
TI  - Tumoral calcinosis.

PMID- 8751712
TI  - The life sciences forum--a call for contributions.

PMID- 8751713
TI  - Constitutive expression of hepatic cytochrome P450 genes.
AB  - Cytochromes P450 are a superfamily of heme proteins involved in oxidative
      metabolism of endogenous chemicals such as steroid hormones and human-made
      xenobiotics including drugs and environmental pollutants. Hundreds of P450s have
      been demonstrated by cDNA and gene cloning in animals, plants, fungi, and
      bacteria. Most of the mammalian xenobiotic-metabolizing P450s, found within the
      eight subfamilies comprising the CYP2 family, are constitutively expressed in the
      liver. Transcriptional activation of individual P450 genes in the liver commences
      at distinct stages of development. Some P450 genes are preferentially expressed
      in one sex. The mechanisms of liver-specific expression of the P450 genes are
      quite diverse. Recent studies have found that several different liver-enriched
      transcription factors including HNF-1 alpha, HNF-3, HNF-4, and C/EBP beta, and
      the more ubiquitously expressed factors Sp1, GABP alpha/beta, and NF2d9 are
      responsible for governing the transcription of P450 genes. In some cases, more
      than one factor can influence expression depending on the developmental stage of
      the animal, and ubiquitously expressed factors such as Sp1 have been found to
      cooperate with liver-enriched factors to maximally activate transcription of P450
      genes. STAT protein- and phospholipase A2-mediated signal transduction have also
      been implicated in sex-dependent expression of certain P450 genes. These studies
      indicate that P450 genes, even within the same subfamily in the same mammalian
      species, can have unique regulatory circuits.-Gonzalez, F. J., Lee, Y.-H.
      Constitutive expression of hepatic cytochrome P450 genes.

PMID- 8751714
TI  - Liver regeneration versus direct hyperplasia.
AB  - Liver cell growth can be induced in two distinct patterns: compensatory
      regeneration and direct hyperplasia. In the former, DNA synthesis is preceded by
      a loss of liver cells such as seen after partial resection of the liver or cell
      necrosis, whereas in direct hyperplasia, DNA synthesis is stimulated without cell
      loss. During the past decade, considerable advances have been made in
      understanding molecular mechanisms of the compensatory regeneration. There is
      increasing evidence that hepatocyte proliferation induced by some primary
      mitogens is mediated by patterns of growth factor modulation and signal
      transduction different from those of compensatory regeneration. Indeed, whereas
      activation of transcription factors such as NF-kappa B and increased expression
      of immediate early genes such as c-fos, c-jun, egr-1, and c-myc are induced
      during compensatory regeneration, such changes are not observed during
      hyperplasia induced by certain primary mitogens. In addition, although
      experimental evidence suggests a critical role for growth factors such as
      hepatocyte growth factor and transforming growth factor-alpha for the progression
      into cell cycle of competent hepatocytes in compensatory regeneration, these
      growth factors do not appear to play a major role in direct hyperplasia. One
      class of primary mitogens may trigger their actions through tumor necrosis factor
      alpha, and the other by activation of nuclear hormone receptors. The differences
      in molecular events observed between liver regeneration and direct hyperplasia
      may affect differently the initiation step of chemical hepatocarcinogenesis.
      Whereas the former supports initiation by chemicals, the latter does not. A
      similar lack of effect on promotion of carcinogen-altered cells has also been
      observed after acute treatment with some primary mitogens. Definition of the
      mechanisms by which primary mitogens stimulate liver cell proliferation may
      elucidate the nature of the signals responsible for triggering the entry into
      cell cycle. Furthermore, due to their low toxicity, primary liver mitogens could
      have significant clinical applications in gene transfer and liver
      transplantation.

PMID- 8751715
TI  - The functional significance of brain metallothioneins.
AB  - Metallothioneins (MTs) are ubiquitous low molecular weight proteins characterized
      by their abundant content of cysteines. Two MT isoforms, MT-I and MT-II, are
      expressed coordinately in all mammalian tissues. In the CNS, MT-I and MT-II are
      conspicuously absent from neuronal populations, yet abundant in fibrous and
      protoplasmic astrocytes. A newly identified brain-specific MT gene, MT-III, is
      predominantly expressed in zinc-containing neurons of the hippocampus and absent
      from glial elements. MTs have been implicated as regulator molecules in gene
      expression, homeostatic control of cellular metabolism of metals, and cellular
      adaptation to stress. MTs store and release essential metals, such as zinc and
      copper, maintaining the low intracellular concentration of free essential metals.
      Thus, MTs fulfill a regulatory capacity and influence transcription, replication,
      protein synthesis, metabolism, as well as other zinc-dependent biological
      processes. Because MT-III is particularly abundant in zinc-containing neurons of
      the hippocampus, it is likely to play an important role in neuromodulation by
      zinc-containing neurons and to act as a sink for free zinc. It may also play an
      etiologic role in various pathophysiological conditions associated with increased
      extracellular zinc. Studies demonstrating that MT-III prevents neuronal sprouting
      in vitro, appears to be down-regulated in Alzheimer's disease, and that MT-III
      "knockout" mice appear highly sensitive to kainateinduced seizures have focused
      growing attention on the etiologic role of MT-III in neurodegeneration.-Aschner,
      M. The functional significance of brain metallothioneins.

PMID- 8751716
TI  - From legumes to leukocytes: biological roles for sulfated carbohydrates.
AB  - Carbohydrates attached to proteins and lipids characteristically display complex
      and heterogeneous structures. However, it is becoming increasingly clear that
      carbohydrates with definite biological functions also exhibit unique structural
      features. A number of glycoproteins and glycolipids have been shown to bear
      oligosaccharides containing sulfate. Often, addition of a sulfate moiety turns a
      relatively common structural motif into a unique carbohydrate with the potential
      to be recognized by a specific receptor or lectin. This is clearly the case in
      three systems in which sulfated oligosaccharides have been shown to play a well
      defined biological role: 1) control of the circulatory half-life of luteinizing
      hormone, 2) symbiotic interactions between leguminous plants and nitrogen-fixing
      bacteria, and 3) homing of lymphocytes to lymph nodes. The rapidly growing list
      of glycoproteins and glycolipids identified as bearing sulfated oligosaccharides
      suggests that sulfated carbohydrates play important biological roles in numerous
      other systems as well.-Hooper, L. V., Manzella, S. M., Baenziger, J. U. From
      legumes to leukocytes: biological roles for sulfated carbohydrates.

PMID- 8751717
TI  - Lipid mediator networks in cell signaling: update and impact of cytokines.
AB  - Biomembranes serve barrier functions and serve as a store for precursors of
      rapidly generated, structurally diverse intracellular and extracellular lipid
      derived mediators (LM). Cell activation is accompanied by remodeling of membrane
      components that appear to be essential in signal transduction. Phospholipases
      (PLA2, PLC, PLD, sphingomyelinase) are pivotal in the generation of these LM
      including eicosanoids, platelet activating factor (PAF), diacylglycerides,
      ceramide, and other newly discovered bioactive autacoids. Cytokines exert a
      dramatic multilevel impact both in regulating enzymes in individual LM pathways
      and in generating LM central to their action. Here, we provide an overview and
      update of recent progress in this area with emphasis on the effect of cytokines
      on LM networks. The generation of eicosanoids (prostaglandins, leukotrienes, and
      lipoxins), oxygenated lipids, and PAF remain the focus of rational drug design
      targets given their established roles in cell-cell communication and as mediators
      in inflammation and pathophysiologic events. Key enzymes in these pathways are
      cloned, sequenced, and their subcellular organization is investigated with
      surprising findings implicating involvement of the nuclear membrane at the
      functional level. Several LM receptors are identified and cloned, and results
      from transgenic animals have emerged for several key enzymes. Novel bioactive
      eicosanoids were discovered, including 15-epi-lipoxins, isoprostanes, and
      isoleukotrienes, that offered new concepts to consider in formation of LM and the
      actions of nonsteroidal anti-inflammatory drugs. Together, these findings
      indicate that LM play critical and essential roles in both signal transduction
      and cell-cell communication and will continue to be important pathways to be
      considered in novel therapeutic approaches.-Serhan, C. N., Haeggstrom, J. Z.,
      Leslie, C. C. Lipid mediator networks in cell signaling: update and impact of
      cytokines.

PMID- 8751718
TI  - Phospholipases: structural and functional motifs for working at an interface.
AB  - Phospholipases form a ubiquitous class of enzymes optimized to catalyze the
      hydrolysis of phospholipids. Because their products are often second messengers,
      they are highly regulated by the cell. For a given ester bond, there are separate
      secreted as well as cytoplasmic phospholipases with different substrate
      specificities and modes of regulation. As it becomes available, structural
      information provides a view of interfacial catalysis for several of these
      phospholipases on a molecular level. Recent structural advances include solution
      structures of a pancreatic phospholipase A2 in the absence and presence of a
      micellar interface, crystal structures of a bacterial phosphatidylinositol
      phospholipase C whose active site is reminiscent of ribonuclease, and a Ca2+
      lipid binding domain with high homology to regions in several cytoplasmic
      phospholipases that can model the way those proteins interact with the membrane
      surface. Phospholipases also have a wide and complex array of regulatory
      mechanisms involving cytoplasmic proteins, notably G-proteins, as well as
      different effector lipids (e.g., phosphatidylinositol-4,5-biphosphate, or PIP2)
      or Ca2+. Deconvolution of these interactions is necessary to understand their
      roles in different signal transduction pathways.-Roberts, M. F. Phospholipases:
      structural and functional motifs for working at an interface.

PMID- 8751719
TI  - Chromatin and transcription.
AB  - The compaction of DNA into chromatin in the eukaryotic nucleus poses many
      obstacles to transcription. Individual nucleosomes as well as higher order
      structures limit access of cis-acting regulatory elements to trans-acting
      factors. The structural nature of this inhibition and the mechanisms by which
      chromatin is remodeled to facilitate the regulation of gene expression have
      remained puzzles for many years. Recent advances highlight the intimate and
      dynamic interplay between transcription proteins and components of chromatin,
      providing new clues to long-standing questions. A transcriptional adaptor complex
      has been discovered to house histone acetylase activity. A chromatin remodeling
      "machine" has been found to be part of the RNA polymerase II holoenzyme.
      Identification of new factors that affect the organization of functional
      chromatin domains in yeast, flies, and mammals provides new insights into the
      organization of higher order chromatin structures, as well as the nature of
      boundaries that restrict these domains. These compelling discoveries and others
      define a new and exciting threshold for our understanding of the many connections
      between chromatin and transcription.

PMID- 8751720
TI  - Regulation of tumor growth and metastasis by thrombospondin-1.
AB  - Thrombospondin-1 (TSP1) is an extracellular matrix glycoprotein that influences
      cell adhesion, motility, and growth. Based on its effects on tumor and
      endothelial cell behavior, this member of the thrombospondin gene family has
      attracted interest as a potential regulator of tumor growth and metastasis.
      Initial studies have confirmed that increased TSP1 expression suppresses growth
      or metastasis of some tumors in vivo and inhibits angiogenesis. These activities
      are cell type specific, however, since overexpression of TSP1 in some tumors
      causes increased tumor progression. One basis for these apparently conflicting
      observations may be the complexity of the protein. TSP1 interacts specifically
      with several cell-surface receptors, heparan sulfate proteoglycans, growth
      factors, and other matrix components. These multiple binding specificities,
      combined with the ability of TSP1 to activate latent transforming growth factor
      beta and inhibit several proteases, suggest that exposure to TSP1 may initiate
      several intracellular signals. The integration of these signals may allow varied
      responses to TSP1. Furthermore, these signals may be received by the tumor cells,
      endothelial cells responsible for neovascularization, stromal cells, or cells of
      the host immune system. TSP1 influences specific behaviors of each cell type.
      Relating these phenomena to the molecular interactions of TSP1 observed in vitro
      may lead to novel therapeutic strategies for controlling cancer progression and
      metastasis.-Roberts, D. D. Regulation of tumor growth and metastasis by
      thrombospondin-1.

PMID- 8751721
TI  - Involvement of interleukin-1 beta-converting enzyme in apoptosis of bFGF-deprived
      murine aortic endothelial cells.
AB  - Apoptosis (programmed cell death) is an essential physiological process that is
      genetically regulated and contributes to the balance between cell growth,
      differentiation, and the maintenance of normal cells. Recent studies show that
      deprivation of growth factor induces apoptosis in endothelial cells. However, the
      molecular mechanisms regulating apoptosis remain unclear. In this study, we
      demonstrate that deprivation of basic fibroblast growth factor (bFGF) increased
      the expression of interleukin-1 beta-converting enzyme (ICE) protein, and
      subsequently induced apoptosis in murine aortic endothelial (MAE) cells. In
      contrast, the proteins of the tumor suppressor p53 and c-myc were undetected
      during apoptosis. This apoptosis was suppressed by the tetrapeptide ICE
      inhibitor, Ac-YVAD-CMK. Overexpression of murine ICE, in addition, induced
      apoptosis in MAE cells using gene transfer techniques. These results strongly
      suggest that ICE may mediate apoptosis in bFGF-deprived endothelial cells, and
      the suppression of ICE function could represent a novel approach for the
      protection of endothelial cells from damages.-Kondo, S., Kondo, Y., Yin, D.,
      Barnett, G. H., Kaakaji, R., Peterson, J. W., Morimura, T., Kubo, H., Takeuchi,
      J., Barna, B. P. Involvement of interleukin-1 beta converting enzyme in apoptosis
      of bFGF-deprived murine aortic endothelial cells.

PMID- 8751722
TI  - Substantial decrease of heat shock protein 90 in ventricular tissues of two
      sudden-death pigs with hypertrophic cardiomyopathy.
AB  - We recently developed a pig model with naturally occurring hypertrophic
      cardiomyopathy (HCM). To further characterize the biochemical features of high
      frequency of sudden death affected by this disease, the protein profiles of
      ventricular tissues were analyzed on normal, HCM, and HCM with sudden-death pigs.
      By sodium dodecylsulfate-polyacrylamide gel electrophoresis, a protein
      corresponding to an apparent molecular mass of 90 kDa (p90) was found to be
      markedly decreased in the HCM-affected tissues of sudden-death pigs, but not in
      HCM or normal pigs. Further study showed that the primary decrease of p90 in HCM
      pigs with sudden death was located mainly in the interventricular septum. As
      determined by the molecular mass and isoelectric point on 2-dimensional gels and
      Western immunoblot with a specific 90 kDa heat shock protein (HSP90) monoclonal
      antibody, the unknown protein was identified as HSP90. Our findings indicate for
      the first time that substantially decreased heart HSP90 is associated with HCM
      pigs with sudden death. Although the role that HSP90 may play in protecting pigs
      with HCM from sudden death is still nuclear, the model itself may provide further
      insight into understanding the role of heat shock proteins in cardiac sudden
      death.-Lee, W.-C., Lin, K.-Y., Chiu, Y.-T., Lin, J.-H., Cheng, H.-C., Huang, H.
      C., Yang, P.-C., Liu, S.-K., Mao, S. J. T. Substantial decrease of heat shock
      protein 90 in ventricular tissues of two sudden-death pigs with hypertrophic
      cardiomyopathy.

PMID- 8751723
TI  - Superiority of in vitro over in vivo calibrations of BCECF in vascular smooth
      muscle cells.
AB  - We measured intracellular pH (pHi) in single vascular smooth muscle cells (VSM)
      cultured from rabbit abdominal aorta, using 2',7'-biscarboxyethyl
      5(6)carboxyfluorescein (BCECF) on a microscope-based fluorimetric system. We
      previously found substantial errors introduced by using high K+/nigericin to
      calibrate intracellular BCECF (1). We also previously demonstrated that the
      necessary correction (pHcor) to the high K+/nigericin-calibrated pHi was linearly
      dependent on pHi, increasing with increasing pHi (2). When the nigericin
      calibration data were corrected using this pHcor, the new corrected calibration
      was similar to the result of calibrating BCECF in vitro (higher Rmax, lower Rmin,
      and lower pK). Therefore, in this study the possibility is considered that in
      vitro calibrations might provide better estimates of pHi. Our best estimate for
      the absolute level of pHi derives from a null method for bracketing steady-state
      pHi. In VSM cells, using only in vitro calibrations to estimate steady-state pHi
      leads to less error (only approximately 0.08 different from null estimates) than
      using nigericin calibrations alone (approximately 0.2 different from null
      estimates). Unlike high K+/nigericin calibrations, the error, pHcor, introduced
      by using an in vitro calibration is pHi independent. Using high K+/nigericin or
      in vitro calibrations, along with the respective pHcor on the same experimental
      days in the same cells, gave the same estimate of pHi whether in the steady
      state, in acid-loaded cells, or in alkali-loaded cells. Similarly, when
      appropriately corrected, both methods gave indistinguishable calibration curves.
      Thus, the two methods are entirely equivalent from the standpoint of accuracy.
      Because nigericin is toxic, expensive, and complicated in its use, we suggest
      that in vitro calibrations, along with simple null determinations to assess the
      small, constant correction factor, be used to calibrate intracellular BCECF.
      Boyarsky, G., Hanssen, C., Clyne, L. A. Superiority of in vitro over in vivo
      calibrations of BCECF in vascular smooth muscle cells.

PMID- 8751724
TI  - Evidence from transgenic mice that glucokinase is rate limiting for glucose
      utilization in the liver.
AB  - To study the role of glucokinase (GK) in the control of glucose metabolism in the
      liver, transgenic mice were generated in which GK was overexpressed under control
      of the P-enolpyruvate carboxykinase gene promoter. Whereas the expression of the
      GK gene in starved control mice was blocked, this promoter was able to direct the
      expression of the enzyme to the liver of starved transgenic mice. Furthermore,
      starved transgenic mice showed levels of GK activity fourfold higher than those
      of starved control and similar to those of fed control. This activation of GK led
      to an increase in the intracellular concentration of glucose 6-phosphate, which
      was also related to an induction of glycogen accumulation. In addition, L
      pyruvate kinase (L-PK) activity increased in transgenic mice, which when starved
      showed similar levels of activity to control fed mice. The induction of L-PK
      caused an increase in the hepatic lactate concentration. Furthermore, hepatocytes
      in primary culture from transgenic mice incubated with 20 mM glucose produced
      levels of lactate threefold higher than controls, but no difference was noted
      when the hepatocytes from control and transgenic mice were incubated with 2 mM
      glucose. These results demonstrated in vivo that the activation of GK is a rate
      limiting step in the induction of glycolysis and glycogen synthesis. These
      changes in liver glucose metabolism led to a marked reduction in blood glucose
      (30%) and insulin (40%) concentrations. Furthermore, transgenic mice showed lower
      levels of blood glucose after an intraperitoneal glucose tolerance test,
      indicating that GK overexpression caused an increase in blood glucose disposal by
      the liver. All these findings show the key role of liver GK in the control of
      whole-body glucose homeostasis.-Ferre, T., Riu, E., Bosch, F., Valera, A.
      Evidence from transgenic mice that glucokinase is rate limiting for glucose
      utilization in the liver.

PMID- 8751725
TI  - Abnormal glutathione and sulfate levels after interleukin 6 treatment and in
      tumor-induced cachexia.
AB  - Excessive urea excretion associated with a negative nitrogen balance and massive
      loss of skeletal muscle mass (cachexia) is a frequent life threatening
      complication in malignancies and HIV infection. As these patients have often
      elevated interleukin-6 (IL-6) and abnormally low cystine levels, we have now
      determined the intracellular levels of glutathione and other cysteine derivatives
      in the liver and muscle tissue of IL-6-treated or tumor-bearing C57BL/6 mice. IL
      6 treatment or inoculation of the MCA-105 fibrosarcoma caused a significant
      increase in hepatic gamma-glutamyl-cysteine synthetase activity and a decrease in
      the sulfate level, glutamine/urea ratio, and glutamine/glutamate ratio,
      suggesting that a decrease of the proton generating cysteine catabolism in the
      liver may increase carbamoyl-phosphate synthesis and urea formation at the
      expense of net glutamine synthesis. Treatment with cysteine, conversely, caused
      an increase in sulfate, glutamine/urea ratios, and glutamine/glutamate ratios and
      may thus be a useful therapeutic tool in clinical medicine. In contrast to the
      liver, muscle tissue of tumor-bearing mice showed decreased glutathione and
      increased sulfate levels, suggesting that the cysteine pool may be drained by an
      increased cysteine catabolism in this tissue. The findings indicate that tumor
      cachexia is triggered initially by IL-6 and is later sustained by processes
      driven by an abnormal cysteine metabolism in different organs.-Hack, V., Gross,
      A., Kinscherf, R., Bockstette, M., Fiers, W., Berke, G., and Droge, W. Abnormal
      glutathione and sulfate levels after interleukin 6 treatment and in tumor-induced
      cachexia.

PMID- 8751726
TI  - Dominant expression of a 1.3 Mb human Ig kappa locus replacing mouse light chain
      production.
AB  - Expression studies of multigene families, such as the immunoglobulin (Ig) loci,
      are difficult because of their large size and the necessity to introduce germline
      configured regions into an animal. Antibody diversity from Ig gene miniloci is
      limited by the number of variable (V) region genes and the need for distal
      regulatory elements to control expression. Here, we show germline transfer into
      mice of a 1300 kb human Ig kappa light chain locus on a yeast artificial
      chromosome that resulted in early DNA rearrangement and highly efficient human
      light chain expression. The human locus was assembled from a 300 kb authentic
      region using contig extension by addition of cosmid multimers to supplement the
      variable gene cluster. This resulted in the addition of about 100 V region genes
      in germline configuration from different families. In transgenic animals with Ig
      kappa disruption, this large human kappa locus replaced the endogenous locus, and
      subsequent down-regulation of Ig lambda light chain contribution led to a
      dominant expression of the rearranged human genes. Contrary to expectation,
      rather than providing a solely selective advantage for ensuring repertoire
      formation controlled by the sheer number of introduced genes, the lambda/kappa
      ratio in serum appears to be the result of competition for early surface Ig
      expression maintained in the developing B cell.-Zou, X., Xian, J., Davies, N. P.,
      Popov, A. V., Bruggemann, M. Dominant expression of a 1.3 Mb human Ig kappa locus
      replacing mouse light chain production.

PMID- 8751727
TI  - New advances in sex preselection.
AB  - OBJECTIVE: To review the current developments in the field of preconceptual sex
      selection and to discuss the moral dilemmas that accompany the scientific
      progress. DESIGN: A survey of the major publications on sex preselection.
      RESULTS: Examination of current methods of preconceptual gender selection
      revealed that in vivo methods such as timing of intercourse, the use of ovulation
      induction medications, and artificial insemination do not appear to affect the
      sex ratio to a clinically significant degree. In vitro separation of X- and Y
      bearing spermatozoa by gradient techniques have been reported to alter
      significantly the sex ratio at birth. However, these trials were noncontrolled,
      and molecular biological techniques could not validate that these methods indeed
      change the Y- to X-bearing spermatozoa ratio sufficiently for clinical use.
      Nevertheless recent scientific advances have made highly reliable preconceptual
      sex selection possible by using preimplantation diagnosis or sperm separation by
      flow cytometry combined with IVF. At present, these methods have been used to
      avoid sex-linked disorders. Both involve the invasive procedure of IVF and thus
      are held by most as inappropriate for nonmedical indications. However,
      improvement in flow cytometry output of sexed spermatozoa might provide in the
      near future sufficient sorted gametes for artificial insemination. This technique
      then will provide an available noninvasive method of sexing for social purposes.
      CONCLUSIONS: Reliable preconceptual sex selection is currently possible only by
      preimplantation diagnosis, or sperm separation by flow cytometry combined with
      IVF. Both methods involve invasive procedures and are at present exclusively used
      for medical indications. It may be that in the near future, an improvement in
      flow cytometry output of sexed spermatozoa will provide sufficient sorted gametes
      for artificial insemination. In such a case, the medical community will be forced
      to take a stand, whether this reliable noninvasive method of sexing will be
      allowed for social purposes.

PMID- 8751728
TI  - The defense against endometriosis.

PMID- 8751729
TI  - Evidence for heterogeneous etiologies of adrenal dysfunction in polycystic ovary
      syndrome.
AB  - OBJECTIVE: To examine the hypothesis that, in polycystic ovary syndrome (PCOS),
      ovarian steroids induce adrenal enzyme dysfunction or adrenal androgen
      hyperresponsiveness to ACTH. DESIGN: Prospective controlled clinical study.
      SETTING: Reproductive endocrinology unit of an academic medical center. PATIENTS:
      Twelve women with PCOS who had adrenal androgen excess were compared with five
      weight-matched ovulatory women. In half of the women with PCOS, prestudy
      screening was suggestive of mild 3 beta-hydroxysteroid dehydrogenase (HSD)
      deficiency. INTERVENTIONS: Basal and adrenal dynamic blood sampling before and
      after GnRH agonist (GnRH-a) administration for 6 months. MAIN OUTCOME MEASURES:
      Basal E2 and androgen levels as well as dexamethasone-suppressed, ACTH-stimulated
      17 alpha-hydroxyprogesterone, 17 alpha-hydroxypregnenolone, and androgen levels
      before and after ovarian suppression. RESULTS: Although none of the subjects with
      PCOS proved to have mild 3 beta-HSD deficiency, the majority of them (58%) met
      the criteria for 17,20 lyase hyperactivity before and after GnRH-a therapy. As a
      group, the remaining subjects with PCOS exhibited an elevated DHEAS response to
      ACTH before GnRH-a treatment, which may have normalized after GnRH-a treatment.
      CONCLUSION: Adrenal androgen excess in PCOS may be heterogeneous in etiology,
      whereas 17,20 lyase hyperactivity appears to be an intrinsic adrenal disorder,
      adrenal androgen hyperresponsiveness to ACTH may be ovarian induced. Reliance on
      historical controls may lead to overdiagnosis of mild 3 beta-HSD deficiency.

PMID- 8751730
TI  - Peritoneal endometriosis and "endometriotic" nodules of the rectovaginal septum
      are two different entities.
AB  - OBJECTIVE: To compare histologically and stereologically the endometriotic nodule
      of the rectovaginal septum to peritoneal endometriosis. DESIGN: Morphometric
      investigation, cytokeratin and vimentin content, and steroid receptor evaluation
      were performed on endometriotic tissue from the peritoneum (n = 52) and
      rectovaginal nodules (n = 68). SETTING: An academic teaching hospital. PATIENTS:
      Biopsies were taken from 120 patients undergoing a laparoscopy for infertility
      and/ or pelvic pain (52 from typical black peritoneal endometriotic implants and
      68 from endometriotic nodule of the rectovaginal septum). None of the patients
      were treated. RESULTS: Mitotic activity was found to be significantly different
      in peritoneal and rectovaginal endometriosis. The evaluation suggested that the
      stroma is not mandatory for the invasion of glandular epithelium in the
      rectovaginal nodule, which is, like a adenomyoma, a circumscribed nodular
      aggregate of smooth muscle and glandular elements. Cytokeratin and vimentin
      content as well as the estrogen receptor (ER) and P receptor (PR) content were
      significantly lower in both types of lesion when compared with eutopic
      endometrium. But vimentin immunoreactivity in epithelium, as well as the ER and
      PR content, were significantly lower in nodules when compared with black
      peritoneal lesions. CONCLUSION: It is suggested that the rectovaginal
      endometriotic nodule is a different disease from peritoneal endometriosis and
      must be called rectovaginal adenomyosis or rectovaginal adenomyoma. Its
      histopathogenesis probably is not related to the implantation of regurgitated
      endometrial cells but to the metaplasia of Mullerian rests.

PMID- 8751731
TI  - Proliferative activity of the endometrium throughout the menstrual cycle in
      infertile women with and without endometriosis.
AB  - OBJECTIVE: To assess whether changes in endometrial proliferation in patients
      with endometriosis contribute to ectopic endometrial implantation. DESIGN:
      Endometrial biopsies from patients with endometriosis were stained
      immunohistochemically and compared with endometrium of a control group (n = 111).
      The newly developed monoclonal antibody Ki-S3 was used as a marker of cellular
      proliferation in surface and glandular epithelia and in stromal cells. SETTING:
      Female Infertility Clinic, Research Centre of Obstetrics, Gynecology, and
      Perinatology, Moscow, Russia, and Institute of Pathology, Christian-Albrechts
      University, Kiel, Germany. PATIENTS: One hundred thirty-nine women with
      endometriosis and 111 women without endometriosis, all being infertile.
      INTERVENTION: Collecting endometrial samples during diagnostic and therapeutic
      laparoscopy. MAIN OUTCOME MEASURE: Number of proliferating cells in endometrial
      stroma, glandular, and surface epithelia. RESULTS: Endometrial proliferation
      showed a characteristic cyclic dependency with greatest activity in the
      follicular phase. Although epithelial proliferation ceased completely during the
      luteal phase, the number of proliferating cells in the stroma increased again
      toward the end of the menstrual cycle after its maximum at ovulation. No
      significant differences could be found between both investigated groups.
      CONCLUSIONS: Endometriosis is not due to an altered proliferative activity in
      eutopic endometrium. Proliferating stromal cells at the end of the menstrual
      cycle may reflect increasing numbers of immunocompetent cells. Endometrium of
      patients with endometriosis reveals almost the same cyclical changes as
      endometrium of patients without endometriosis does. Further attention to cells
      and cell-mediated reactions in the extrauterine milieu is required to elucidate
      the pathogenesis of endometriosis.

PMID- 8751732
TI  - Analysis of the karyotype and desoxyribonucleic acid content of uterine myomas in
      premenopausal, menopausal, and gonadotropin-releasing hormone agonist-treated
      females.
AB  - OBJECTIVE: To correlate the cytogenetics and the DNA content in uterine myomas.
      DESIGN: Prospective study in treated and untreated females. SETTING: Tertiary
      University Center. PATIENTS: Premenopausal, menopausal, and GnRH-agonist (GnRH-a)
      treated patients. INTERVENTION: Myomectomy or hysterectomy. MAIN OUTCOME MEASURE:
      Karyotype analysis and the DNA content measured by microfluorescence technique
      and expressed in fluorescence units. RESULTS: The mean DNA content in cells from
      karyotypically normal and karyotypically abnormal myomas, respectively, was 37.4
      +/- 6.9 and 30.4 +/- 1.8 fluorescence units in premenopausal females, 30.3 +/-
      5.3 and 28.7 +/- 0.9 fluorescence units in menopausal females, and 31.6 +/- 2.7
      and 32.9 +/- 5.8 fluorescence units in GnRH-a-treated females. CONCLUSIONS: Forty
      percent of the myomas evaluated demonstrated an abnormal karyotype and had a
      significantly lower DNA content than the chromosomally normal myomas. After GnRH
      agonist treatment, the DNA content was decreased in the euploid myoma group only.

PMID- 8751733
TI  - Endometrial thickness is predictive of histologic endometrial maturation in women
      undergoing hormone replacement for ovum donation.
AB  - OBJECTIVE: To determine if ultrasonographic endometrial pattern or thickness is
      predictive of histologic endometrial maturation in women undergoing hormone
      replacement for ovum donation. DESIGN: Ultrasonographic endometrial thickness and
      pattern were determined and compared with histologic assessment of endometrial
      maturation. PATIENTS: Forty-six women underwent 52 preparatory cycles for ovum
      donation. Transvaginal ultrasound (US) was performed after 14 days of E2
      replacement and, after 12 days of P, an endometrial biopsy was performed. In 12
      cycles, a continuous dose of 2 mg/d E2 was administered. In cycles with out-of
      phase biopsies (dated earlier than day 24) and in the last 34 cycles, all women
      received an escalating dose of E2 before initiation of P. Additionally, the 46
      women underwent 55 ETs with USs performed on cycle day 15. RESULTS: Six women had
      abnormal biopsies in their first preparatory cycle on the continuous E2 protocol,
      which normalized with the escalating protocol. All other women had normal
      biopsies. Women with abnormal biopsies had significantly thinner endometrium (<
      or = 6 mm) but similar endometrial patterns compared with women with normal
      biopsies. In women having US in preparatory and transfer cycles, there were no
      differences in endometrial thickness or pattern between examinations.
      CONCLUSIONS: Endometrial thickness > or = 7 mm in hormone replacement cycles
      predicts in phase endometrial histology and can replace the endometrial biopsy.

PMID- 8751734
TI  - Lactose metabolism and time to pregnancy.
AB  - OBJECTIVE: To investigate whether, in the absence of galactosemia, relatively
      high intestinal lactase activity or low activity of an enzyme involved in
      galactose catabolism reduces fertility, as it does in the presence of
      galactosemia. DESIGN: Retrospective cohort study. SETTING: Healthy women selected
      from the community. PATIENTS: Fifty-three married women. INTERVENTION: Urinary
      galactose after an oral lactose challenge (a measure of intestinal lactase
      activity), erythrocyte galactose-1-phosphate uridyltransferase (transferase)
      activity, and transferase polymorphisms by isoelectric focusing. MAIN OUTCOME
      MEASURE: Pregnancy rate (number of pregnancies divided by number of months at
      risk) in the 12 months after stopping use of birth control to become pregnant.
      RESULTS: Relatively high urinary galactose was not related to a decreased rate of
      pregnancy during the first 12 months (> or = 24.6 compared with < or = 14.3 mg:
      relative risk [RR] = 1.9; 95% confidence interval [CI] = 0.86 to 4.0). Relatively
      high transferase activity was not related to an increased rate of pregnancy (> or
      = 19.5 compared with < or = 17.2 mumol/h per g hemoglobin: RR = 1.1; 95% CI =
      0.56 to 2.4). Low-activity transferase polymorphisms were not related to a
      decreased rate (RR = 1.2; 95% CI = 0.58 to 2.5). CONCLUSION: Our study does not
      support the hypothesis that the biologic variation in galactose metabolism that
      exists in the general population influences infertility.

PMID- 8751735
TI  - Hormone replacement therapy modifies the capacity of plasma and serum to regulate
      prostacyclin and endothelin-1 production in human vascular endothelial cells.
AB  - OBJECTIVE: To determine if hormone replacement therapy (HRT) modifies the ability
      of plasma or serum to regulate the synthesis of vasodilatory prostacyclin and
      that of vasoconstrictive endothelin-1 by cultured human umbilical vein
      endothelial cells. DESIGN: Plasma and serum collected before and during the sixth
      treatment cycle of HRT from 13 healthy postmenopausal women were added to
      cultured endothelial cells. SETTING: Helsinki University Central Hospital,
      Department of Obstetrics and Gynecology, Helsinki, Finland. PATIENTS: Thirteen
      postmenopausal women (> or = 1 year since their last menstruation, FSH level > 40
      mIU/mL [conversion factor to SI unit, 1.00], clear vasomotor symptoms) that
      suffered from incapacitating menopausal symptoms necessitating the initiation of
      HRT were studied. INTERVENTIONS: A combined regimen consisting of 2 mg oral E2
      for 12 days followed by 2.0 mg oral E2 + 1.0 mg norethisterone acetate for 10
      days and 1.0 mg E2 for 6 days. MAIN OUTCOME MEASURES: The releases of
      prostacyclin, as assessed by its metabolite 6-keto-prostaglandin F1 alpha, and
      that of endothelin-1 by cultured human umbilical vein endothelial cells in the
      presence of 10% plasma or 10% serum collected from the study subjects. RESULTS:
      Hormone replacement therapy enhanced the ability of plasma to stimulate
      prostacyclin production by 21% +/- 6% (mean +/- SEM) during the E2 +
      norethisterone acetate phase and tended to do so also during the E2-only phase
      (11% +/- 10%) but caused no change in endothelin-1 release. In contrast, HRT
      decreased the ability of serum to stimulate prostacyclin production by 12% +/- 5%
      during the E2-only phase and increased that of endothelin-1 by 8% +/- 4% during
      the E2 + norethisterone acetate phase. CONCLUSION: Because plasma flushes
      endothelial cells in vivo, our data on the HRT-induced stimulation of the
      capacity of plasma to enhance the production of vasoprotective prostacyclin
      without a concomitant change in endothelin-1 release in cultured human umbilical
      vein endothelial cells may provide one new explanation for the cardiovascular
      protection of HRT.

PMID- 8751736
TI  - Pregnancy rates after communal growth of preimplantation human embryos in vitro.
AB  - OBJECTIVE: To evaluate the effect of communal growth of preimplantation human
      embryos on pregnancy rates in IVF-ET. DESIGN: Prospective randomized study.
      SETTING: In Vitro Fertilization Unit, Bikur Cholim Hospital, Jerusalem, Israel.
      PATIENTS: Ninety-one women undergoing 91 cycles of IVF-ET. INTERVENTION: In 42
      cycles (control) embryos were grown singly, in 49 cycles (study) embryos were
      grown in groups until transfer. MAIN OUTCOME MEASURES: Proportion of women
      achieving pregnancy in study and control groups. RESULTS: Communal growth of
      embryos resulted in significantly improved pregnancy rates. Intrauterine transfer
      of embryos grown in groups produced 43% pregnancy rates per transfer, whereas,
      with embryos grown individually, 24% pregnancy rates were obtained (odds ratio =
      2.4). CONCLUSIONS: Our study suggests that, in IVF, the potential of
      preimplantation human embryos to produce pregnancy tends to increase when embryos
      are grown in groups.

PMID- 8751737
TI  - Effect of in vitro fertilization on human chorionic gonadotropin serum
      concentrations and Down's syndrome screening.
AB  - OBJECTIVE: To investigate the association between IVF and Down's syndrome
      screening analytes (alpha-fetoprotein [AFP] and hCG) during the second trimester.
      DESIGN: Retrospective analysis. SETTING: University-based tertiary care
      infertility clinic. PATIENTS: Data on 41 consecutive singleton IVF pregnancies
      and 4,935 naturally occurring singleton pregnancies. RESULTS: Maternal serum hCG
      concentrations were elevated (mean 1.52 multiples of the median [MoM]) in IVF
      pregnancies, whereas there were no significant differences in AFP levels (mean
      1.02 MoM). The mean maternal age was higher in the subjects than in controls
      (33.8 compared with 28.7 years). In relation to Down's syndrome risk assessment,
      the pattern of the two markers, together with maternal age, indicated high risk
      more often in the study subjects than in the controls. In vitro fertilization
      patients had a false-positive rate of 26.8% compared with 6.6% in women without
      fertility problems. CONCLUSION: The increased false-positive rate in Down's
      syndrome screening is related not only to advanced maternal age but also, in
      part, to the elevated hCG concentrations observed in pregnancies after assisted
      reproduction. The mechanism behind increased hCG production remains to be
      elucidated, but it may be an effect associated with infertility or the procedures
      by which these women conceive. To provide an objective assessment of an
      individual patient's risk of fetal abnormality, the impact of IVF on hCG
      biochemistry should be studied further in larger samples and adjustments made if
      appropriate.

PMID- 8751738
TI  - Laparoscopically assisted gamete intrafallopian transfer with local anesthesia
      and intravenous sedation.
AB  - OBJECTIVE: To determine the length of procedure, length of recovery, patient
      tolerance, complications, and pregnancy rate (PR) of laparoscopically assisted
      GIFT performed during local anesthesia with i.v. sedation. DESIGN: A
      retrospective study. SETTING: Freestanding private ambulatory surgical center.
      PATIENTS: Thirty-one consecutive couples with infertility. INTERVENTIONS:
      Laparoscopically assisted GIFT during local anesthesia with i.v. sedation. MAIN
      OUTCOME MEASURES: Surgery time, recovery time, patient tolerance, PR, miscarriage
      rate, and complications. RESULTS: Cannulation of at least one fallopian tube was
      achieved successfully in all patients. The average surgery time was 64 +/- 12
      minutes (mean +/- SD). The average recovery time was 92 +/- 30 minutes. The PR
      was 39% with an ongoing PR of 32%. There were no intraoperative or postoperative
      complications. CONCLUSION: Local anesthesia with IV sedation for GIFT using a two
      puncture laparoscopic technique was well tolerated by the patients. Our ongoing
      PR of 32% compares very favorably with other series using general anesthesia.

PMID- 8751739
TI  - Clinical parameters influencing human zona pellucida thickness.
AB  - OBJECTIVES: To assess which clinical parameters influence human oocyte zona
      pellucida (ZP) thickness. PATIENTS: Sixty-five couples undergoing 75 IVF-ET
      cycles. MAIN OUTCOME MEASURE: Zona pellucida thickness of 827 oocytes measured 16
      to 20 hours after in vitro insemination under inverted light microscope. RESULTS:
      Zona pellucida thickness was 18.9 +/- 3.8 microns (mean +/- SD) for unfertilized,
      16.4 +/- 3.1 microns for fertilized, and 15.1 +/- 2.4 microns for polyspermic
      oocytes (significantly different). Among our patients, a few underwent two (or
      even three) IVF-ET cycles, and the mean ZP thickness was, in most cases, not
      significantly different from one cycle to the other(s). Regression analyses were
      calculated between ZP thickness and available clinical parameters, i.e., the age
      of the women, the duration of stimulation, the cumulus maturity, the number of
      retrieved oocytes, the number of hMG doses, the maximum E2 level, and the
      follicular volume. A significant linear decreasing relationship exists between
      the mean ZP thickness of each patient and the maximum E2 level and an increasing
      one with the hMG dose. Relationships with the other parameters appeared to be
      nonsignificant. CONCLUSION: The ZP thickness is basically an individual feature
      that influences the fertilization rate. Nevertheless, it may be influenced
      slightly by the hormonal treatment during stimulation.

PMID- 8751740
TI  - Effect of abnormal hypo-osmotic swelling test on fertilization rate and pregnancy
      outcome in in vitro fertilization cycles.
AB  - OBJECTIVE: To assess the value of the hypo-osmotic swelling test in predicting
      fertilization, pregnancy, implantation, miscarriage, and live birth rates in IVF
      ET cycles. DESIGN: Prospective study. SETTING: Academic tertiary referral center
      for fertility treatment. PATIENTS: Three hundred twenty-six couples having IVF-ET
      for tubal damage or male factor infertility with the female partner < 38 years of
      age. INTERVENTIONS: Each male had a hypo-osmotic swelling test performed between
      4 and 8 weeks before IVF-ET. MAIN OUTCOME MEASURES: Fertilization, implantation,
      miscarriage, and live birth rates. RESULTS: Eighty of 326 men had abnormal hypo
      osmotic swelling tests. An abnormal test was not associated with lower
      fertilization rates (odds ratio [OR] = 1.14; 95% confidence interval [CI] = 0.97
      to 1.14) or pregnancy rate (OR = 0.98; CI = 0.50 to 1.96). However, although
      couples with a normal test had a miscarriage rate of 26.9% (14/52), in the group
      with an abnormal test the miscarriage rate was 50.0% (7/14) (OR = 0.37; CI = 0.09
      to 1.49). This resulted in a reduction in the live birth rate from 14.1% in the
      group with a normal test to 11.8% in patients with an abnormal test (OR = 1.23;
      CI = 0.45 to 3.87). CONCLUSIONS: The hypo-osmotic swelling test has little value
      in predicting fertilization in IVF-ET procedures. However, an abnormal test may
      help predict adverse outcome if pregnancy is achieved.

PMID- 8751741
TI  - Status of the coagulation and fibrinolytic systems in ovarian hyperstimulation
      syndrome.
AB  - OBJECTIVE: To elucidate characteristic changes of plasma hemostatic markers in
      ovarian hyperstimulation syndrome (OHSS) cycles. DESIGN: Prospective study.
      SETTING: The IVF-ET program of the Department of Obstetrics and Gynecology, The
      University of Akita, School of Medicine. PATIENTS: Forty cycles of 40 IVF
      patients, including 12 cycles in which a severe form of OHSS occurred.
      INTERVENTIONS: Blood samples were taken during IVF treatment to determine the
      levels of blood markers that reflect activation of the coagulation and
      fibrinolytic systems. MAIN OUTCOME MEASURES: Thrombin-antithrombin III complexes,
      plasmin-alpha 2 antiplasmin complexes, and other hemostatic markers related to
      the coagulation and fibrinolytic system activation. RESULTS: In the OHSS cycles,
      the levels of thrombin-antithrombin III and plasmin-alpha 2 antiplasmin complexes
      in the plasma began to rise within a few days after hCG administration and
      demonstrated significantly higher levels during the midluteal phase. In OHSS
      cycles with pregnancy, elevation of these markers continued for > or = 3 weeks
      after the onset of disease. There were some characteristic changes in OHSS cycles
      in other hemostatic markers, such as a decrease in the levels of antithrombin III
      and prekallikrein and shortened activated partial thromboplastin time.
      CONCLUSION: These data demonstrate the status of the coagulation and fibrinolytic
      systems in OHSS cycles and provide insight into the mechanism of activation in
      the hemostatic system.

PMID- 8751742
TI  - Autologous granulosa cell coculture demonstrates zygote suppression of granulosa
      cell steroidogenesis.
AB  - OBJECTIVE: To determine if embryos can modulate steroid hormone production by
      luteinized granulosa cells. DESIGN: Granulosa cells obtained from follicular
      aspirates were cultured alone or in the presence of a two-pronuclear zygote. The
      production of E2 and P by these cultures was evaluated by RIA. SETTING: In Vitro
      Fertilization Unit in an academic research environment. PATIENTS: Sixteen women
      undergoing IVF. INTERVENTIONS: Standard IVF-ET treatment cycle using leuprolide
      acetate for pituitary desensitization before hMG or urofollitropin for ovarian
      stimulation. MAIN OUTCOME MEASURES: Estradiol and P concentration in culture
      media of luteinized granulosa cells alone or granulosa cells cocultured with a
      two-pronuclear embryo. RESULTS: Both E2 and P production by luteinized granulosa
      cells was reduced when cultured in the presence of an embryo. CONCLUSIONS: Human
      embryos secrete a factor that regulates granulosa cell steroidogenesis.

PMID- 8751743
TI  - The effect of antioxidant treatment on human spermatozoa and fertilization rate
      in an in vitro fertilization program.
AB  - OBJECTIVE: To study the possible influence of antioxidant treatment on human
      spermatozoa and the fertilization rate in an IVF program. DESIGN: Prospective
      study. SETTING: In Vitro Fertilization Unit, Serlin Maternity Hospital, and the
      Laboratory of Male Fertility, Bar-Ilan University, Ramat-Gan, Israel. PATIENTS:
      Fifteen fertile normospermic male volunteers who had low fertilization rates in
      their previous IVF cycles. INTERVENTIONS: Vitamin E (alpha-tocopherol) 200 mg
      daily by mouth for 3 months. MAIN OUTCOME MEASURES: Lipid peroxidation potential
      (amount of malondialdehyde [MDA]), quantitative ultramorphologic analysis of
      spermatozoa, and fertilization rate per cycle. RESULTS: The high MDA levels
      significantly decreased from 12.6 +/- 9.4 nmol/10(8) spermatozoa to normal levels
      of 7.8 +/- 4.2 nmol/10(8) spermatozoa after 1 month of treatment. The
      fertilization rate per cycle increased significantly from 19.3 +/- 23.3 to 29.1
      +/- 22.2 after 1 month of treatment. No additional effects on MDA levels and
      fertilization rate were observed after completion of treatment. With regard to
      the quantitative ultramorphologic analysis, none of the sperm cell subcellular
      organelles were affected significantly by vitamin E treatment. CONCLUSION:
      Vitamin E may improve the fertilization rate of fertile normospermic males with
      low fertilization rates after 1 month of treatment, possibly by reducing the
      lipid peroxidation potential, and with no change of the quantitative
      ultramorphologic analysis of subcellular organelles.

PMID- 8751744
TI  - Therapeutic cup insemination with cryopreserved donor sperm: prognostic value of
      cervical mucus score at insemination and the number of motile sperm in mucus at
      24 hours.
AB  - OBJECTIVE: To examine the prognostic value of cervical mucus score at
      insemination and the number of motile sperm in mucus 24 hours after therapeutic
      cup insemination with cryopreserved donor sperm. DESIGN: Retrospective analysis.
      SETTING: Academic tertiary medical center. PATIENTS: One hundred thirty-eight
      women with confirmed bilateral tubal patency who received therapeutic cup
      inseminations with cryopreserved donor sperm between 1986 and 1993.
      INTERVENTIONS: All insemination cycles were monitored with serial daily urinary
      LH determinations with a single (n = 312) insemination or two inseminations (n =
      212) performed on and/or 1 day after the day of LH surge detection. A single
      examiner assigned cervical mucus scores in all insemination cycles and recorded
      the number of motile sperm in mucus 24 hours after the first insemination in dual
      insemination cycles. MAIN OUTCOME MEASURE: Pregnancy rate during various cervical
      mucus and motile sperm scores. RESULTS: Ninety-one women conceived (66%) and
      seven of these achieved two pregnancies. The overall pregnancy rate per
      insemination cycle was 18.7%. Age and day of insemination were the only variables
      identified as having significant influence on cycle outcome. Pregnancy occurred
      with decreasing frequency as patient age increased and was nearly twice as likely
      after insemination on the day after the urinary LH surge as on the day of surge
      detection. CONCLUSIONS: Insemination the day after the urinary LH surge is
      superior to the day of surge detection. Cervical mucus score and the number of
      motile sperm in mucus 24 hours after therapeutic cup insemination with
      cryopreserved donor sperm do not correlate with cycle outcome.

PMID- 8751745
TI  - Computer-assisted semen analysis parameters in men with varicocele: is surgery
      helpful?
AB  - OBJECTIVE: To assess sperm characteristics and fertility before and after
      varicocelectomy using computer-assisted semen analysis (CASA). DESIGN:
      Preoperative and postoperative sperm parameters of infertile men with varicocele
      were analyzed statistically and the outcome of pregnancy was determined. SETTING:
      Department of Infertility Management and Assisted Reproduction, Jaslok Hospital
      and Research Centre, Bombay. PATIENTS: Semen samples of 49 men with varicocele
      related infertility were analyzed using CASA. INTERVENTIONS: Sperm parameters of
      26 men who underwent varicocelectomy were evaluated 3, 6, and 9 months
      postoperatively. Conception, occurring either naturally or therapeutically, was
      recorded. MAIN OUTCOME MEASURES: Evaluation of improvement of sperm parameters
      after surgery. RESULTS: Sperm count, motility parameters, curvilinear velocity,
      straightline velocity, lateral head displacement, and normal morphology were
      significantly lower in men with varicocele. Postoperatively, there was
      significant improvement in count, motility, and normal morphology, with a
      decrease in proportion of acrosome-deficient heads and tapering forms. After
      varicocelectomy, 46.2% of the men had normal semen parameters, with the overall
      pregnancy rate being 50%. CONCLUSIONS: Computer-assisted semen analysis provides
      the potential for accurate quantitative evaluation of semen in men with
      varicocele. Varicocelectomy results in improvement in semen quality with
      pregnancy rates of 50%.

PMID- 8751746
TI  - Motility and other characteristics of human sperm can be measured by computer
      assisted sperm analysis of samples stained with Hoechst 33342.
AB  - OBJECTIVE: To develop methods for using a DNA-specific dye to discriminate
      between motile and nonmotile sperm and static particulate matter in fresh and
      diluted semen, using computer-assisted sperm analysis (CASA) with the Hamilton
      Thorne IVOS, TOX version (Hamilton-Thorne Research, Beverly, MA). DESIGN: Donor
      semen was divided for treatment as fixed stained sperm (Hoechst 33342 stain;
      Sigma Chemical Company, St. Louis, MO), fresh motile and nonmotile stained sperm,
      and unstained control sperm. SETTING: Normal human volunteers in an academic
      research and medical environment. PATIENTS: Selected healthy student volunteers.
      INTERVENTIONS: Delivered semen to the laboratory within 1 hour of collection.
      MAIN OUTCOME MEASURE: Semen quality measured by CASA. RESULTS: Fixed or fresh
      human sperm stained with Hoechst 33342 dye should be diluted to < or = 50 x 10(6)
      sperm/mL to count sperm accurately. Motile and nonmotile sperm were stained
      suitably with 5 to 10 micrograms/mL of dye when diluted with a simple diluent,
      but the dye concentration should be increased to 40 micrograms/mL when egg yolk
      is in the diluent. CONCLUSIONS: The DNA-specific dye, Hoechst 33342, can be used
      to discriminate between motile and nonmotile sperm and other particulate matter
      when evaluated by CASA with instrumentation equipped with suitable optics.

PMID- 8751747
TI  - Evaluation for antisperm antibodies after storage of sperm in TEST-yolk buffer.
AB  - OBJECTIVE: To determine if TEST-yolk buffer, consisting of TES (N-tris
      [hydroxymethyl]-methyl-2-aminoethanesufonic acid), Tris
      (Tris[hydroxymethyl]aninomethane), and chicken egg yolk, affects the presence of
      antisperm antibodies on the sperm surface as detected by the immunobead test.
      DESIGN: A prospective study of antisperm antibodies on sperm surface before and
      after incubation in TEST-yolk buffer. Direct immunobead test and indirect
      immunobead test were done the day of collection of the semen sample to detect the
      presence of human immunoglobulin class G (IgG) and immunoglobulin class A (IgA);
      immunobead tests were repeated on the same sperm samples after 24 hours of
      storage in TEST buffer. SETTING: Academic tertiary institution. PARTICIPANTS:
      Patients undergoing evaluation for infertility. RESULTS: There was no significant
      difference in the outcome of the direct immunobead test after extending semen
      samples with TEST-yolk buffer for 24 hours at 4 degrees C. Eleven samples that
      were initially negative for IgG and 13 samples that were negative for IgA
      remained negative after 24-hour storage in TEST-yolk buffer. Eleven samples that
      were positive for IgG and nine samples that were positive for IgA by the direct
      immunobead test the first day remained positive the next day. Five extended sperm
      samples used in the indirect immunobead test with IgG positive serum gave
      positive results and four of five used with IgA positive serum gave positive
      results. CONCLUSIONS: These findings suggest that TEST-yolk buffer can be used to
      extend semen without affecting the presence of antibodies on the sperm surface as
      indicated by the direct immunobead test. The higher variability of the indirect
      immunobead tests indicates there may be some alteration of sperm antigens after
      storing in TEST-yolk buffer. These findings indicate that TEST-yolk buffer can be
      used to store semen for batched processing of samples or as a transport medium
      for delivery to a central laboratory for antibody testing.

PMID- 8751748
TI  - Glass wool column filtration versus mini-Percoll gradient for processing poor
      quality semen samples.
AB  - OBJECTIVE: To compare the quality and number of spermatozoa recovered from
      laboratory-induced severe oligozoospermic specimens processed by mini-Percoll
      gradient and glass wool column filtration. DESIGN: Both sperm-processing
      procedures were compared in similar sperm samples adjusted to contain equal low
      numbers of motile spermatozoa using either dilution (oligozoospermia) or with the
      addition of killed sperm (oligoasthenozoospermia). The spermatozoa processed by
      both procedures samples were evaluated for motility, response to hypo-osmotic
      swelling test, and the hemizona assay. PATIENTS: Five healthy fertile sperm
      donors. SETTING: Private Andrology Laboratory and University Hospital. MAIN
      OUTCOME MEASURE: Sperm motility, hypo-osmotic swelling test, and hemizona assay
      results determined the efficacy of the sperm-processing procedures. RESULTS: The
      concentration of sperm recovered after both procedures was not affected by either
      preparation or processing methods. Glass wool-processed sperm had higher motility
      in oligoasthenozoospermic samples, bound tightly to hemizonae in higher mean
      numbers, and demonstrated a higher percentage of membrane-intact spermatozoa in
      oligozoospermic samples. CONCLUSION: Laboratory-prepared oligozoospermic samples
      subjected to glass wool filtration yielded more functionally intact spermatozoa
      than mini-Percoll gradient processing.

PMID- 8751749
TI  - Polymerase chain reaction-based detection of bacteria in semen.
AB  - OBJECTIVE: To determine if the presently used bacterial detection techniques
      provide accurate and complete profiles of microorganisms found in human semen.
      DESIGN: Routine bacterial cultures and molecular biology techniques using
      polymerase chain reaction (PCR), with a universal eubacterial primer, cloning,
      then sequence analysis were used to detect bacteria (culturable or nonculturable)
      in the semen. SETTING: University and hospital-based research laboratory.
      PATIENTS: Thirty infertile men and nine semen donors, all with no symptoms of a
      urinary tract infection, donated semen for the study. INTERVENTIONS: None. MAIN
      OUTCOME MEASURES: Detection of bacteria using routine cultures and molecular
      biology techniques. RESULTS: Using PCR, we found > 10(4) bacteria/mL in the semen
      of 66% of the infertile asymptomatic men and 66% of the semen donors. This
      contrasts with our routine culture results which detected "significant"
      bacteriospermia in only 27% of the infertile men and in none of the preselected
      semen donors. From four of these semen specimens, DNA sequence analysis
      identified an average of nine different bacterial species per specimen, with
      close to 90% of the species being anaerobes. CONCLUSIONS: These data indicate
      that the present microbiologic detection methods underestimate the incidence of
      significant bacteriospermia, particularly anaerobic bacteria. The molecular
      biologic methods should help researchers confirm or refute the role of infection
      in male infertility.

PMID- 8751750
TI  - Ectopic growth of endometrium depends on its structural integrity and proteolytic
      activity in the cynomolgus monkey (Macaca fascicularis) model of endometriosis.
AB  - OBJECTIVE: To identify factors influencing the development of endometrial
      autografts in a monkey model of endometriosis. DESIGN: Prospective, comparative
      study. SETTING: Animal research unit. SUBJECTS: Thirty regularly cycling
      cynomolgus monkeys in three groups of 10 each. INTERVENTIONS: Endometrium was
      minced and spilled into the cul-de-sac in group 1. In group 2, the tissue
      additionally was digested enzymatically. In group 3, the tissue was incubated
      with a protease inhibitor. MAIN OUTCOME MEASURES: Staging laparotomies after 3
      weeks and 3 months. RESULTS: In groups 1, 2, and 3, moderate or severe disease
      was seen in eight, two, and four monkeys, respectively, after 3 weeks and in
      eight, three, and two monkeys, respectively, at 3 months. CONCLUSIONS: An intact
      structure leads to ectopic implantation of endometrial fragments in most cases.
      Conversely, enzymatic digestion of endometrial fragments and treatment with
      proteinase inhibitor impair ectopic growth. Intrinsic endometrial factors that
      influence extracellular matrix remodeling may play a role in the pathogenesis of
      human endometriosis.

PMID- 8751751
TI  - Endometrial stripe thickness as a predictor of ectopic pregnancy.
AB  - OBJECTIVE: To evaluate the potential utility of endometrial stripe thickness in
      predicting pregnancy outcome in women with an hCG less than a discriminatory
      zone. DESIGN: Retrospective case review. SETTING: University emergency
      department. PATIENTS: Women who presented with symptomatic early pregnancies
      after a spontaneous conception with an hCG level less than a discriminatory zone
      evaluated to rule out an ectopic pregnancy (EP). INTERVENTIONS: Measure
      endometrial stripe thickness by transvaginal ultrasound. MAIN OUTCOME MEASURES:
      Initial endometrial stripe thickness was correlated to eventual pregnancy
      outcomes. RESULTS: The mean initial endometrial stripe thickness of patients
      eventually diagnosed with an intrauterine pregnancy (13.42 +/- 0.68 mm),
      spontaneous abortion (9.28 +/- 0.88 mm), and an EP (5.95 +/- 0.35 mm) were all
      statistically different from each other. Ninety-seven percent of pregnancies
      found to have an endometrial stripe thickness < or = 8 mm were abnormal (EP or
      spontaneous abortion). CONCLUSIONS: This study suggest a role of the evaluation
      of the endometrial stripe thickness in the detection of abnormal pregnancies in
      patients presenting for evaluation of a symptomatic early pregnancy with an hCG
      below a discriminatory zone. Initial endometrial stripe thickness measured in
      patients with an EP is significantly thinner than in those with an intrauterine
      pregnancy.

PMID- 8751753
TI  - Yeast infection of sperm, oocytes and embryos after intravaginal culture for
      embryo transfer.
AB  - OBJECTIVE: To report a case of an embryo culture infected with Candida albicans
      after intravaginal culture. DESIGN: Case report. SETTING: Private infertility
      practice and university medical center. PATIENT: A couple with tubal and male
      factor infertility. INTERVENTIONS: Superovulation, oocyte recovery, Percoll sperm
      preparation, and intravaginal culture of sperm and oocytes in a tissue culture
      tube. MAIN OUTCOME MEASURES: Yeast infection of sperm, oocyte, and embryo
      culture. RESULTS: Candida albicans infection occurred in the sperm, oocyte, and
      embryo culture when cultured in a sealed tube in the vagina. Candida albicans
      also was found in the prepared sperm suspension culture in a separate tube kept
      in a 37 degrees C incubator. CONCLUSIONS: Infection of the embryo culture with C.
      albicans probably occurred when contaminated sperm was added at the time of
      insemination. Sperm preparation by the Percoll gradient centrifugation failed to
      eliminate C. albicans in the semen.

PMID- 8751752
TI  - Pulmonary edema: a complication of local injection of vasopressin at laparoscopy.
AB  - OBJECTIVE: To report a case of pulmonary edema after local injection of
      vasopressin at laparoscopy. SETTING: University teaching hospital. PATIENT: A 24
      year-old woman who underwent a laparoscopic myomectomy. INTERVENTION: Injection
      of vasopressin (10 mL of 0.5 U/mL) into the uterine wall overlying the myoma.
      RESULTS: Bradycardia, atrioventricular block, and pulmonary edema. CONCLUSIONS:
      The use of vasopressin can be associated with severe cardiopulmonary
      complications.

PMID- 8751754
TI  - Ovulation induction in clomiphene-resistant anovulatory women with normal
      dehydroepiandrosterone sulfate levels: beneficial effects of the addition of
      dexamethasone during the follicular phase.
AB  - OBJECTIVE: To evaluate the effect on ovulation of a 10-day course of
      dexamethasone (DEX) initiated concurrently with a 5-day course of clomiphene
      citrate (CC) in CC-resistant patients with normal DHEAS levels. DESIGN:
      Retrospective review. SETTINGS: Patients from the clinical practice of the
      authors at the Medical College of Georgia, Augusta, Georgia. PATIENTS: Thirteen
      oligomenorrheic women with normal DHEAS levels who failed to ovulate on a
      graduated regimen of CC up to a dose of 150 mg for 5 days. INTERVENTIONS: Ten-day
      course of DEX initiated concurrently with a 5-day course of CC; ovulation and
      pregnancy outcomes recorded. MAIN OUTCOME MEASURE: Pregnancy. RESULTS: Eleven of
      13 women had evidence of ovulation. Five clinical pregnancies were achieved.
      CONCLUSION: These initial data support improvements in follicular development
      with an overlapping follicular phase regimen of CC and DEX in patients with
      normal DHEAS levels and a previous poor response.

PMID- 8751755
TI  - Endometriosis and polycystic ovary syndrome: enhanced stimulatory effect of
      peritoneal fluid on progesterone release from human granulosa-lutein cells.
AB  - OBJECTIVE: To compare the activity of peritoneal fluid (PF) from women with and
      without endometriosis or polycystic ovary syndrome (PCOS) on P release from
      cultured human granulosa-lutein cells. DESIGN: Case-control study. SETTING:
      Medical school and hospital. PATIENTS: Women with mild to moderate endometriosis
      or PCOS and controls undergoing laparoscopic sterilizations. MAIN OUTCOME
      MEASURES: Human granulosa-lutein cells, obtained from the IVF clinic, were
      cultured with increasing volumes of steroid-extracted PF samples with and without
      hCG. Progesterone concentrations in the media after 72 hours culture were
      measured by RIA. RESULTS: Peritoneal fluid stimulated P release in a dose
      dependent manner and, at the highest dose, the response was enhanced
      significantly by PF from women with endometriosis and PCOS compared with control
      samples. The effects of PF plus hCG were not simply additive. There was a large
      potentiation of the response, which was greater in women with endometriosis and
      PCOS. CONCLUSIONS: Peritoneal fluid contains factors that stimulate P release and
      potentiate the response to hCG. The increased activity of PF associated with
      endometriosis and PCOS in part may have some significance in abnormal ovarian
      function associated with these syndromes.

PMID- 8751756
TI  - Sex determination by simultaneous application of polymerase chain reaction and
      fluorescent in situ hybridization on the same blastomere of a pre-embryo.
AB  - OBJECTIVE: To describe an investigation of the feasibility of carrying out
      polymerase chain reaction (PCR) and fluorescent in situ hybridization on the same
      single human cell for sex determination. DESIGN: To develop protocol for a
      clinical diagnostic test in preclinical trials. SETTING: Infertile human
      volunteers in a clinical environment. PATIENTS: Polyploid embryos were obtained
      from patients treated by IVF at the Advanced Institute of Fertility.
      INTERVENTIONS: Seventeen blastomeres biopsied from human polyploid embryos were
      analyzed for sex determination by simultaneous application of PCR and fluorescent
      in situ hybridization. MAIN OUTCOME MEASURE: Presence of an X- or X and Y
      chromosome band after agarose gel electrophoresis of PCR products and presence of
      an X- or X and Y-chromosome fluorescent probe signal after fluorescent in situ
      hybridization following PCR analysis. RESULTS: By PCR, all 17 blastomeres were
      amplified and, by fluorescent in situ hybridization, 12 (70.6%) blastomeres
      produced signals that were consistent with PCR results. Two blastomeres showed
      only X signals, although by PCR they had both X and Y-chromosome bands.
      CONCLUSIONS: The sequential use of PCR and fluorescent in situ hybridization on
      the same blastomere can be applied to improve the accuracy of sex determination
      before fresh ET.

PMID- 8751757
TI  - The "P-C" world of medicine: a commentary on the current medical scene.

PMID- 8751758
TI  - ASA physical status and age are not factors predicting morbidity, mortality, and
      survival after pancreatoduodenectomy.
AB  - To evaluate the effects of age and physical status on postoperative
      complications, American Society of Anesthesiologists-Physical Status score (ASA
      score) and age were analyzed in patients undergoing pancreatoduodenectomy (PD).
      Medical records and follow-up results of 69 patients who had undergone PD from
      1980 to 1993 at one institution were examined. Clinical variables affecting
      morbidity and mortality rates were analyzed, and compared between two-aged groups
      (> or = 70 years (n = 18) and < 70 (n = 51)). Univariate Cox regression analysis
      of 69 patients showed that ASA score and age were not significant factors
      affecting postoperative morbidity, mortality, and survival. The clinical
      variables including ASA score, gender, operative time, blood loss, stage, and
      location of carcinoma were similarly distributed between the two-aged groups. The
      mortality rate in patients less than 70 years of age was 5.9 per cent (3/51),
      whereas there was no mortality in patients more than 70 years of age. The
      morbidity, mortality, and cumulative survival rates were statistically similar in
      the two age groups. The results suggest that ASA-physical status and age are not
      limiting factors for PD and do not predict survival. The procedure is safe and
      worthwhile even in patients more than 70 years of age with the ASA score up to
      III.

PMID- 8751759
TI  - Spontaneous duodenal perforation in neonates: a case report and review of
      literature.
AB  - Although duodenal perforation in neonates is an extremely rare entity, it should
      be suspected in any case with signs of viscus perforation. If found in the
      absence of possible causes, duodenal perforation is considered to be spontaneous.
      It is believed to be of multifactorial origin. Once found primary closure with or
      without omental patching is the treatment of choice. In this article we describe
      one case of spontaneous perforation and analyze the possible causes.

PMID- 8751760
TI  - Treatment and prognosis of primary malignant small bowel tumors.
AB  - Primary malignant tumors of the small bowel are a heterogeneous group of tumors
      and are uncommon compared to tumors in other locations of the gastrointestinal
      tract. These tumors have been traditionally associated with a poor prognosis. The
      charts of 53 patients with primary malignant small bowel tumors at major Eastern
      Virginia Medical School teaching hospitals were retrospectively reviewed. Patient
      characteristics and presenting symptoms and signs were nonspecific. No single
      radiographic or endoscopic procedure was performed on every patient, and the
      diagnosis was suspected preoperatively in only 50 per cent of the patients.
      Tumors were most common in the ileum, and the most common histologic types were
      adenocarcinoma (53 per cent) and carcinoid (32 per cent). In univariate analysis,
      factors determining survival included histologic type, location of tumor, and
      stage. There was also a trend toward worse survival in patients receiving
      chemotherapy or radiation therapy, possibly due to patient selection factors. In
      multivariate analysis, only histology and stage significantly influenced
      survival. The overall 10-year survival of the entire group was 44 per cent. Small
      bowel tumors have a variable prognosis. A high index of suspicion and more
      frequent use of enteroclysis may lead to earlier detection and improved survival.

PMID- 8751761
TI  - Primary malignant melanoma of the esophagus: diagnostic value of endoscopic
      ultrasonography.
AB  - Primary malignant melanomas of the esophagus have been clinically diagnosed as
      exophytic tumors by esophagography and esophagoscopy. We first applied endoscopic
      ultrasonography to the tumors; the tumors were demonstrated as "submucosal
      tumors" and smooth-surfaced with clear margins, and their internal echo
      architectures depended upon the tumor sizes. We consider the disease can be
      clinically diagnosed by the above three diagnostic modalities.

PMID- 8751762
TI  - Superficial fine needle aspiration by clinicians: a survey of utilization.
AB  - Quality assurance is as much concerned with cost, turnaround time, and use of
      resources as with test reliability and outcome. The cytopathologist needs to be
      aware of the knowledge base and expectations of clinicians who perform fine
      needle aspiration (FNA) biopsies of superficial lesions without technical
      assistance. To this end, a single correct answer multiple choice questionnaire
      was sent to 82 procedure-oriented clinical faculty members. Completed answer
      sheets from 35 faculty members were analyzed. The score for fee and turnaround
      time was 63.2 per cent and for knowledge of technique 70.6 per cent. The overall
      score for use of FNA was 64.7 per cent and for specimen handling was 45.6 per
      cent. Of those 65 per cent of participants who made comments, 30 per cent
      stressed importance of shorter turnaround time and 27 per cent emphasized the
      need for training in this area of endeavor. It is concluded that the quality of
      diagnosis can be improved by placing greater emphasis on training and education,
      the provision of written material, courses or tutorials in technique, written and
      verbal feedback regarding specimen adequacy, and by making more extensive use of
      electronic transmission of results.

PMID- 8751763
TI  - Intrahepatic arterial chemoembolization for hepatocellular carcinoma and
      metastatic neuroendocrine tumors in the era of liver transplantation.
AB  - Surgical resection has been the standard approach for primary and metastatic
      liver tumors. Long-term survival, however, is limited because of recurrence or
      hepatic decompensation. Failure of chemotherapeutic regimens or liver
      transplantation (OLT) to prevent recurrence has resulted in the need for
      multimodality therapies. We report our experience with preoperative hepatic
      arterial chemoembolization (CET) followed by OLT in highly select patients. Over
      a 33-month period, 23 of 41 patients (56%) referred with primary (n = 16) or
      metastatic neuroendocrine (n = 7) liver tumors met eligibility requirements.
      Despite mild, self-limited chemical hepatitis, CET was well tolerated in all but
      three elderly patients who succumbed to liver failure. Four of five patients
      ultimately received OLT. Three are alive and free of disease at a mean followup
      of 17 months, one died of recurrent hepatocellular carcinoma, and one (NET)
      remains well at 33 months with elevated glucagon levels but no measurable
      disease. All NET patients are alive with resolution of hormonal symptoms. Four of
      five noncirrhotic patients died of disease, and one has progressive tumor growth.
      Although OLT following CET achieves superior survival, its application is limited
      to a minority of patients with such tumors. Careful pretreatment staging and
      patient selection combined with caution in the use of CET in elderly cirrhotic
      patients is critical to the success of such therapies.

PMID- 8751764
TI  - The effects of octreotide on healing of small bowel anastomosis.
AB  - Octreotide (OCT) is a somatostatin analog used for its inhibitory action on
      multiple GI functions. Although octreotide has numerous clinical benefits, it has
      also been shown to inhibit postresectional hyperplasia of small bowel and hepatic
      regeneration. Because octreotide inhibits both trophic and anabolic hormones, we
      hypothesize that the use of octreotide may be detrimental in patients with a
      recent bowel anastomosis. To test this hypothesis, 60 male rats were randomized
      to four equal groups following small bowel anastomosis. Group I = control; Group
      II = 10 mg/day of hydrocortisone succinate; Group III = 2.5 micrograms/kg/day
      octreotide (equivalent of a clinical dose); Group IV = 25 micrograms/kg/day
      octreotide. Hydrocortisone was used as a negative control because it is known to
      have inhibitory effects on small bowel anastomotic healing. On postoperative Day
      7, bursting pressures were measured. Serum T-kininogen levels, as a marker for
      systemic inflammation, and hydroxyproline content from the anastomotic segments
      were obtained. These results indicate that in the rat small bowel model,
      octreotide did not have any deleterious effect on anastomotic strength, systemic
      inflammation, and collagen content, even at high doses. Hydrocortisone, as
      expected, showed significant detrimental effects on bursting strength, as well as
      decreasing systemic inflammation. These findings have significant clinical
      implications, as octreotide could be used without jeopardizing the intestinal
      anastomosis.

PMID- 8751765
TI  - Stereotactic breast biopsy: improved tissue harvesting with the Mammotome.
AB  - The current study was performed to determine whether the Mammotome, a new breast
      biopsy instrument, is better at harvesting breast tissue percutaneously than an
      automated Tru-Cut (ATC) device. A total of 345 stereotactic breast biopsies were
      performed with the Mammotome. The Mammotome specimens were clinically evaluated
      on a five-point specimen scale that reflected the quality and quantity of the
      specimens and the rapidity of collection. In selected cases, specimen weights
      from both techniques were measured. In addition, by examining the lesion site
      post-biopsy, biopsies were categorized as incisional or excisional. Specimens
      obtained with the Mammotome were two times heavier than when obtained with the
      Biopty gun (34.3 mg vs. 17.2 mg, P < or = 0.0002). When aggregate Mammotome
      specimen weights were regressed against number of specimens submitted, average
      weight per specimen was 31.9 mg (P < or = 0.0001). When compared with the ATC
      device on the specimen scale, the Mammotome specimens were rated "Average" in 2.1
      percent, "Good" in 13 percent, and "Very Good" in 84.9 percent. Also, 51.9
      percent of the biopsies with the Mammotome were judged to be incisional; 48.1
      percent, excisional. Three minor complications were encountered. The Mammotome
      more quickly harvests more breast tissue compared with ATC technology.

PMID- 8751766
TI  - Metastatic breast carcinoma presenting as cholecystitis.
AB  - We report two cases of metastatic breast cancer presenting as cholecystitis. Each
      patient had undergone a mastectomy years earlier. Biopsy of the gallbladder
      removed during cholecystectomy revealed metastatic infiltrating ductal carcinoma
      in one patient and infiltrating lobular carcinoma in the other.

PMID- 8751767
TI  - Carcinoma of the breast metastatic to the ureter presenting with flank pain and
      recurrent urinary tract infection.
AB  - Urinary tract infection in the female patient is not an uncommon finding. Flank
      pain associated with urinary tract infection is usually due to calculus disease
      or pyelonephritis. In patients with history of breast carcinoma, metastasis to
      the periureteral area with resulting obstruction should be considered. The
      incidence of metastatic breast carcinoma presenting in this fashion is as high as
      7.8 per cent. This case shows a patient with metastatic lobular carcinoma of the
      breast with ureteral obstruction, causing flank pain and recurrent urinary tract
      infection. This report emphasizes the importance of long-term follow-up in
      patients with history of breast cancer, especially invasive lobular carcinoma,
      and the high degree of suspicion required to diagnose and institute proper
      therapy.

PMID- 8751768
TI  - Spontaneous pneumothorax in the AIDS population.
AB  - Spontaneous pneumothorax (SP) in patients with acquired immunodeficiency syndrome
      (AIDS) has become the leading cause of nontraumatic pneumothorax in the urban
      population. However, the appropriate treatment, especially the role of surgical
      intervention, remains controversial. A retrospective study of 33 patients with
      AIDS who were treated for 38 episodes of SPs (5 bilateral SPs) at our institution
      was conducted. The study consisted of 25 males (76%) and 8 females (24%) with a
      mean age of 38 years. Concurrent Pneumocystis carinii pneumonia was detected in
      29/33 patients (88%). Three forms of treatment were utilized for the 38
      pneumothoraces (5 of which required two modalities): closed tube thoracostomy,
      28/38 (group 1); observation alone, 10/38 (group 2); and operative procedures,
      5/38 (group 3). There were eight hospital deaths, four following resolution of
      the SP. Follow-up was available for 14 patients, 11 of whom died a median of 3
      months post-discharge. Three patients were alive 1, 3, and 18 months post
      discharge. AIDS-related SP is strongly associated with Pneumocystis carinii
      pneumonia and is predictive of a short-term survival. The treatment should be
      individualized, and, although resolution of the pneumothorax can be expected, the
      coexisting AIDS-related illnesses determine the outcome.

PMID- 8751769
TI  - Acute cholecystitis resulting from hemobilia after tru-cut biopsy: a case report
      and brief review of the literature.
AB  - Acute cholecystitis following hemobilia is very rare, with only five cases
      reported in the literature. A case report of a 22-year-old woman who underwent a
      liver biopsy for staging of Hodgkin's lymphoma and developed cholecystitis due to
      hemobilia is presented. The incidence of hemobilia has increased with the advent
      of more invasive hepatobiliary procedures, but the mortality has been decreasing
      due to better recognition and therapy. Acute cholecystitis associated with
      hemobilia is very rare, but will be seen with increasing frequency; and a high
      index of suspicion needs to be maintained to ensure timely diagnosis and
      treatment.

PMID- 8751770
TI  - Retroperitoneal and abdominal wall emphysema after transanal excision of a rectal
      carcinoma.
AB  - The use of transanal excision to remove rectal carcinomas is a relatively new
      application of this surgical procedure, which may require full thickness
      excision. Retroperitoneal and abdominal wall emphysema are potential
      complications of surgical procedures that breach the wall of the colon and
      rectum. Computed tomographic scans provide the clearest diagnostic picture of
      developing emphysema, and prompt diagnosis through accurate interpretation of the
      scans is essential to minimize morbidity and mortality. When the diagnosis is
      made early and no active infection accompanies the emphysema, the preferred
      approach to initial treatment is nonsurgical. This article presents a case in
      which local transanal excision was performed on a 70-year-old male to remove a
      superficial adenocarcinoma from the lower rectal wall. He developed postoperative
      retroperitoneal and abdominal wall emphysema. Conservative treatment is
      discussed.

PMID- 8751771
TI  - Technique of sacral hernia repair.
AB  - After sacrectomy, a hernial defect may develop through the pelvic floor at the
      reconstructed sacral bed. This complication has not previously been described. We
      describe a technique for repair of such a defect using a prosthetic patch.
      Accurate and safe repair of this hernia requires correct preoperative diagnosis
      and planning, including a thorough knowledge of pelvic floor anatomy.

PMID- 8751772
TI  - Presacral drainage in penetrating extraperitoneal rectal injuries: is it
      necessary?
AB  - The objective was to evaluate the need for presacral drainage in low velocity
      penetrating rectal injury. Standard management of penetrating injuries to the
      extraperitoneal rectum from high velocity injury consists of debridement,
      diversion, drainage, and distal washout. A retrospective, descriptive review of
      penetrating rectal injury from 1983 to 1993 was undertaken. Independent variables
      included age, sex, injury severity score, mechanism of injury, caliber of weapon,
      associated injuries, pre-/intra-/postoperative antibiotics, length of stay, and
      presacral drainage. Dependent variables included wound infection and intra
      abdominal abscess. Twenty-two consecutive patients met inclusion criteria. Mean
      injury severity score was 14.2 (SD +/- 2.3). Proximal colostomy was performed on
      20; distal washout in 12 (60%). Eight (40%) of the 20 underwent presacral
      drainage; 12 (60%) did not. Use of presacral drainage was based on attending
      surgeon's preference. Groups were comparable regarding all independent variables.
      Routine use of presacral drainage in managing low velocity rectal wounds may not
      be necessary. Absence of drainage did not increase infectious complications.

PMID- 8751773
TI  - Spermatic cord hematoma: case report and literature review.
AB  - Spermatic cord hematoma is a rare diagnosis. The etiology may be idiopathic,
      traumatic, secondary to anticoagulation therapy, or as an extension of a
      retroperitoneal hemorrhage. It has been misdiagnosed as an incarcerated inguinal
      hernia, a testicular torsion, or a tumor. A review of the English literature is
      presented. An additional case is presented here as a complication of
      anticoagulation therapy after aortic valve replacement. Risk factors for a
      spermatic cord hematoma may warrant an ultrasound examination.

PMID- 8751774
TI  - Colon perforation, bilateral pneumothoraces, pneumopericardium,
      pneumomediastinum, and subcutaneous emphysema complicating endoscopic
      polypectomy: anatomic and management considerations.
AB  - A case of colonoscopic polypectomy complicated by perforation, pneumoperitoneum,
      bilateral pneumothoraces, pneumopericardium, pneumomediastinum, and subcutaneous
      emphysema is presented. The anatomic basis for the various clinical presentations
      of extraluminal air following colonoscopy as well as the option of conservative
      therapy of select cases of perforation is discussed.

PMID- 8751775
TI  - Testicular atrophy and neuropathy in herniorrhaphy.
AB  - This study is based upon our collective experience with more than 3000 open
      herniorrhaphies, dissection of 99 cadavers from the external approach, and 39
      cadavers from open dissections, including 14 laparoscopic dissections. These
      observations may be of use in avoiding pitfalls in hernioplasty, either from the
      classic external surgical approaches or those from within, whether
      transperitoneal or preperitoneal.

PMID- 8751776
TI  - Sven Ivar Seldinger.

PMID- 8751777
TI  - The preparation of advanced practice nurses. Current issues.
AB  - The changes and challenges that nurses face today are preparation for the future.
      Incorporating ongoing refinements in practice directed toward improving patient
      outcomes and maintaining the willingness to be visionary in the preparation of
      nurses for the advanced practice nurse role bode well for the future. This
      article addresses the history of, need for, and educational preparation of
      advanced practice nursing.

PMID- 8751778
TI  - Nurse midwifery. Advanced practice nursing?
AB  - This article traces the roots and history of nurse-midwifery in the United States
      in order to demonstrate the reality of midwifery as a profession in its own
      right. From its beginnings in the late 1920s, the profession has gradually
      evolved from its clear roots in nursing to an identity of its own expressed
      through its professional organization, the American College of Nurse-Midwives. A
      review of other countries' experiences with midwifery reflect much of the U.S.
      process and results. The future challenge for both professions is to determine
      how they can exist in harmony, recognizing that they are complementary roles.

PMID- 8751780
TI  - Primary care across clinical settings.
AB  - This article discusses the role of the Family Nurse Practitioner. It is a
      personal account of the nurse practitioner role across the clinical spectrum of
      office, infirmary, hospital, and home care settings. General information is
      provided on professional liability, prescriptive authority, and other practice
      issues. An evaluation of the multi-faceted role of the nurse practitioner is
      provided.

PMID- 8751779
TI  - The role of the psychiatric nurse practitioner.
AB  - Policy, organizational management, and research roles have received little
      attention in this article because the focus has been on the practice role. It
      must be noted, however, that psychiatric nurse practitioners often assume these
      roles. Many psychiatric nurse practitioners have discovered that their expertise
      in communication and systems assessment prepares them well for policy and
      management positions. The influence of public and private policy on practice and
      the lives of mentally ill persons has led psychiatric nurse practitioners to
      become active in the public policy arena. Similarly, psychiatric nurse
      practitioners' grounding in practice and training in research allows for
      participation in planning and conducting studies that will inform policy makers
      as the mental health reform process continues. The psychiatric nurse practitioner
      title and role have evolved in response to regulatory desire for consistent
      titling of advanced practice nurses and community need for practitioners with the
      skills in assessment, psychotherapy, psychopharmacology, and care management.
      Nursing academic institutions are working to develop new programs to prepare the
      psychiatric nurse practitioners of the future in the wide range of skills needed
      for this role. Practice subspecialties and settings vary, but in all instances
      the psychiatric nurse practitioner offers a blend of nursing and psychiatric
      specialty care that, in many cases, is substitutive for that of a psychiatrist.
      In the current era of health-care reform, fiscal constraint, and burgeoning
      health-care technology, the practice, research, and policy roles available to and
      occupied by psychiatric nurse practitioners are many. The primary threat to full
      actualization of the psychiatric nurse practitioners' potential is that advanced
      practice nursing will choose to be wedded to anachronistic ideologies regarding
      nurse practitioners and clinical specialists.

PMID- 8751781
TI  - Nurse-managed primary care center.
AB  - The authors look at many aspects of a nurse-managed primary care center within an
      academic institution, as administrators and practicing clinicians. This article
      presents the history of the development of the center, the profile of clients and
      services, the education and preparation for the role of nurse practitioner and
      scope of practice, reimbursement, legal issues such as collaborative practice and
      barriers to practice, and risk management. Problems faced by many nurse-managed
      centers are addressed, especially the need for flexibility, with personal
      accounts of how they have been dealt with at this center. An evaluation of the
      center and its practice model is offered.

PMID- 8751782
TI  - The advanced practice nurse in an acute care setting. The nurse practitioner in
      adult cardiac surgery care.
AB  - Growing numbers of nurse practitioners are shifting practice to the acute care
      setting. Nurse practitioners are responding to the demand by hospitals for more
      efficient, cost effective, and safe patient care. An Adult Cardiac Surgery
      program in New York City uses acute care nurse practitioners in providing patient
      care through the hospital course. This article explores one such practice.

PMID- 8751783
TI  - Nurse practitioner in a rural setting.
AB  - The author details her experiences as a nurse practitioner in rural southeast
      Missouri. The passage of Missouri House Bill 564 encouraged greater utilization
      of nurse practitioners to provide primary care. This article shares some of the
      frustrations, joys, and trials by fire of the author. Among the issues presented
      are practice issues, prescriptive authority, professional liability, evaluation
      of practice, and changes for the future.

PMID- 8751784
TI  - The nurse practitioner in the school setting.
AB  - This article discusses primary care as it is provided in a school-based health
      center by a nurse practitioner and a health care team. The description of the
      practice includes the population served, the range of services, obstacles to
      care, future goals, and job satisfaction of the nurse practitioner.

PMID- 8751785
TI  - The psychiatric clinical specialist in the home care setting.
AB  - The Psychiatric Clinical Specialist (PCS) in home care is a richly diverse
      clinical role that combines all aspects of a traditional Clinical Nurse
      Specialist with the challenging components of a Case Manager. Independent
      functioning, creativity, and dedication are vital to the success of such an
      endeavor. The rewards are many, including the opportunity to provide holistic
      nursing care to clients and their families within the natural setting of the
      home. As more clients return home after shortened hospital stays, the need for
      ongoing research to demonstrate the effectiveness of home care for the
      psychiatric client is an urgent issue to be addressed. The advanced practice PCS
      in home care is in a vital position to take on this cause.

PMID- 8751786
TI  - Case management in the community setting.
AB  - This article describes a federally funded nurse managed community health
      organization that treats the elderly. The innovative community-focused model uses
      the nurse as case manager to provide health promotion, screening, and early
      interventions to clients enrolled in the Community Nursing Organization (CNO). It
      explains the advantages of integrating advanced practice nurses into the nursing
      staff to provide both direct care to clients and teaching/conculation to the
      nursing staff. The CNO demonstrates that advanced practice nurses possess
      autonomous practice skills and are able to integrate preventive and curative care
      across practice sites.

PMID- 8751787
TI  - The clinical nurse specialist in geriatrics in Utrecht, The Netherlands.
AB  - The Clinical Nurse Specialist (CNS) position is relatively new in The
      Netherlands; of all the hospitals, only 25% have active CNSs. In University
      Hospital Utrecht, there are five CNSs, with one in geriatrics. The goal of the
      author is to further develop nursing knowledge in geriatrics. Emphasis is given
      to patient care, education, innovation, and research. Since the beginning the CNS
      history in 1992, much has been achieved.

PMID- 8751788
TI  - Independent nurse practitioner. Advanced nursing practice in Brisbane, Australia.
AB  - Within the last decade, changes have been witnessed in nursing practice,
      including Queensland, Australia. These changes occurred when nursing underwent
      restructuring in most states of Australia. The result was that the focus moved to
      recognize clinical expertise rather than years of service. This change in focus
      provided a career path for professional nursing practice. The author presents her
      own experiences and discusses all of the important aspects of advanced practice
      nursing in this country.

PMID- 8751789
TI  - The nurse anesthesia profession. A past, present, and future perspective.
AB  - The author presents a very detailed description of the history of the nurse
      anesthetist, including a time line of important dates in history. Discussion of
      the present state of affairs in nurse anesthesia centers around the practice
      setting, requirements for attaining Certified Registered Nurse Anesthetist (CRNA)
      status, and educational qualifications and capabilities. The article ends with a
      brief history and current status of the American Association of Nurse
      Anesthetists as well as a discussion about the future of the CRNA.

PMID- 8751790
TI  - Legal aspects of nurse anesthesia practice.
AB  - The legality of nurse anesthesiology practice has followed the history of the
      profession. Initial challenges to the legality of the practice were the primary
      legal focus, whereas current legality involves anti-trust, reimbursement, and
      vicarious liability issues. The profession has prevailed in the courts but
      continues to be the subject of legal debate. This article reviews the legal
      history of the profession and uses case law to validate the various legal
      challenges in the areas of malpractice, licensure law, and practice issues.

PMID- 8751791
TI  - Clinical aspects of nurse anesthesia practice: monitoring and decision making.
AB  - This article discusses how nurse anesthetists use clinical monitoring to make
      decisions that guide anesthetic administration. The importance of both didactic
      and clinical knowledge in making appropriate clinical decisions is examined. A
      multi-system approach is applied to investigate the various types of clinical
      monitoring used to observe the patient undergoing general or regional anesthesia.

PMID- 8751792
TI  - Clinical aspects of the preanesthetic evaluation.
AB  - The ultimate goal of preanesthetic evaluation and preparation of the patient is
      reduction of morbidity and mortality of surgery and anesthesia. Using advanced
      practice nursing skills of therapeutic communication, physical assessment, and
      attainment of a health history, the CRNA plans and implements the safest possible
      plan of anesthetic care.

PMID- 8751793
TI  - Clinical aspects of CRNA practice. General anesthesia.
AB  - General anesthesia is a state of reversible, descending depression of the central
      nervous system that is induced by inhalational or intravenous drugs. Components
      of general anesthesia include hypnosis, analgesia, amnesia, and muscle
      relaxation. Recognized anesthesia providers include CRNAs and anesthesiologists.
      Improvements in pharmacologic agents, technology, and education of providers have
      sharply reduced morbidity and mortality associated with anesthesia.

PMID- 8751794
TI  - Clinical aspects of CRNA practice. Regional anesthesia.
AB  - Regional techniques have become increasingly popular for anesthesia and analgesia
      for surgical patients. It is also frequently used for the patient with
      nonsurgical pain such as cancer. New discoveries in physiology, pharmacology,
      pain modulation and transmission as well as pain management therapies are a
      dynamic field of study in regional anesthesia and analgesia. Nurse-anesthetists
      provide regional techniques as part of their armamentarium of clinical skills.

PMID- 8751795
TI  - Clinical aspects of nurse anesthesia practice. Sedation and monitored anesthesia
      care.
AB  - Safe monitoring of patients receiving sedation mandates that all care givers
      recognize the potential physiologic trespass of sedatives, hypnotics, and opioid
      like drugs on cerebral or respiratory systems. They must be ready to recognize
      this affront immediately, have necessary resuscitative equipment available,
      possess prerequisite skills to intervene in adverse changes, and know when to
      seek additional help. The long history of CRNA practice has helped to define
      nursing roles in this important form of perioperative care.

PMID- 8751796
TI  - [Epidemiology of hepatocellular carcinoma].
AB  - Hepatocellular carcinoma (HCC), which constitutes the majority of primary liver
      cancer, is endemic to certain areas of the world. The incidence rate varies
      considerably from area to area, and the difference between Mozambique, South
      Africa, and northern Europe in the age group of 25 to 34 years is more than 500
      fold in males. It now seems that the area along the Yangtse River to the north of
      Shanghai, China, has an incidence rate just as high as Mozambique. Such
      differences are due to the predominant etiologic factors such as aflatoxin B1,
      and hepatitis B and C virus infections. While the hepatitis B infection rate is
      decreasing among HCC patients, hepatitis C infection has been increasing in the
      population and in HCC patients in some countries, such as Japan, Italy and Spain.
      Regardless of the area, males are more prone to HCC than females, and this ratio
      is also changing with time in some countries because of the change in the
      relative proportion of hepatitis B and C among patients. The known etiologic
      factors, such as hepatitis B, hepatitis C, Budd-Chiari syndrome and chemical
      carcinogens, are briefly reviewed.

PMID- 8751797
TI  - [Chemotherapy of small cell lung cancer].
AB  - Chemotherapy of small cell lung cancer is reviewed. Combination chemotherapy with
      cisplatin/etoposide (PE) or CAV (cyclophosphamide, adriamycin and vincristine)
      alternating with PE was established as standard regimens. Dose intensive
      chemotherapy, such as weekly regimens or using G-CSF, is being investigated. In
      patients with limited disease (LD), combined modality treatment is proven to
      produce favorable results, but the best sequence or fractionation of thoracic
      radiotherapy is unknown. More progress in the treatment of small cell lung cancer
      is expected.

PMID- 8751798
TI  - [Chemotherapy for recurrent ovarian cancer].
AB  - The standard treatment for ovarian cancer is cytoreductive surgery followed by
      platinum-based combination chemotherapy. Although high response rates of this
      treatment are reported, 40-60% of patients achieving a complete response may
      relapse. Therefore, second-line chemotherapy is required. Second-line
      chemotherapy of patients with recurrent ovarian cancer should be based on their
      sensitivity to first-line chemotherapy and the platina-free interval. Patients
      who respond to the platina-based chemotherapy still may be sensitive to further
      platina-based chemotherapy. Patients who do not respond to the platina-based
      chemotherapy or who have relapses shortly after first-line chemotherapy should be
      considered clinically resistant to further platina-based chemotherapy. For such
      patients the chemotherapy regimen should be changed. These regimens include
      paclitaxel and hexamethylmelamine. The effect of intraperitoneal chemotherapy may
      depend on the size of the largest residual tumor nodule and the patient's
      sensitivity to previous chemotherapy.

PMID- 8751799
TI  - [Salvage therapy for refractory testicular cancer].
AB  - Cisplatin-based conventional chemotherapy followed by surgery can cure 80-70% of
      disseminated testicular cancers. Effective salvage therapy is required for the
      remaining 20-30% of patients. High-dose chemotherapy (HDCT) combined with
      autologous stem-cell rescue for refractory testicular tumor results in about 10
      20% durable complete responses. Hematologic toxicity is severe, and about 10%
      treatment-related deaths were reported in early investigations. Early salvage
      therapy or first-line therapy using HDCT is under investigation to improve
      treatment efficacy of the refractory or poor-risk testicular cancer. One of the
      important findings of these trials is that a platinum analogue may be critical to
      HDCT for cisplatin-refractory cases. Recent basic research has showed that
      platinum-containing anticancer drug provokes a complex response in the cancer
      cells. It is hoped that investigation of the mechanism of cisplatin-resistance or
      development of a new platinum complex will overcome the limitations of salvage
      chemotherapy for this disease. Finally, several investigators reported that
      highly selected chemorefractory patients, even with positive tumor markers, have
      definite potential for cure with surgical resection of localized metastatic
      disease. Thus, salvage surgery may be indicated for patients refractory to all
      potentially curative chemotherapeutic regimens.

PMID- 8751800
TI  - [Head and neck cancer].
AB  - Before CDDP was clinically used, combination chemotherapy regimens like BLM +
      MMC, VCR + MTX-LV + BLM, VCR + MTX-LV + BLM + MMC had been used for recurrent
      tumors of the head and neck. In a phase II study with CDDP, we experienced two
      patients with long-term survival (12, 15+) who were treated with CDDP as a second
      line chemotherapy for recurrent tumors. Cisplatin was evaluated as a potentially
      curative agent. After that, CDDP based regimens have been used as neo-adjuvant
      setting (first-line chemotherapy). So it became quite difficult to make up a
      second-line chemotherapy since CDDP based regimens have been used as the first
      line chemotherapy. We conducted basic research on second-line chemotherapy for
      recurrent head and neck cancer: (1) cross-resistance studies on head and neck
      cancer cell lines resistant to CDDP, 5-FU, MTX and BLM; (2) second line
      chemotherapy for CDDP + PEP combination chemotherapy, which was developed by us,
      in human KB cell line; and (3) effects of etoposide plus mitomycin C on head and
      neck squamous cell carcinoma in monolayer and multicellular tumor spheroid. Based
      on our long-term experience with chemotherapy for head and neck cancer, and the
      results of the above-mentioned basic research, we established a policy to select
      second-line chemotherapy for recurrent head and neck cancer, especially in cases
      previously treated with chemotherapy.

PMID- 8751801
TI  - [Non-Hodgkin lymphoma].
AB  - In a prospective randomized trial conducted by SWOG, CHOP has shown equivalent
      efficacy to second and third generation combinations, while the toxic death rate
      by CHOP was the smallest among regimens studied. The group thus concluded that
      CHOP remains the best available treatment. However judging from past results it
      is not definitive that CHOP is standard. Many investigators therefore have
      studied to obtain higher efficacy than by CHOP. Regimens for higher dose
      intensity with the support of G-CSF, and high dose chemotherapy with the support
      of autologous hematopoietic stem cells, are under way and current results are
      reviewed.

PMID- 8751802
TI  - [Dual biochemical modulation therapy using 5-FU, leucovorin and cisplatin on
      human rectal carcinoma xenografts in nude mouse].
AB  - This study examined a combined treatment for colorectal carcinoma, the dual
      biochemical modulation therapy, consisting of 5-FU, Leucovorin (LV) and Cisplatin
      (CDDP). We compared its anti-tumor effects with other treatments: 5-FU alone,
      CDDP alone and 5-FU with LV. Primary diffuse infiltrated colorectal carcinoma is
      well known for its biological malignancy and its lack of response to
      chemotherapy. We used SRM cells from a cell line of carcinoma of the rectum, and
      subcutaneously injected them into nude mice. The anti-tumor effects were
      estimated from the growth rate, inhibition rate and thymidylate synthetase
      inhibition rates in the tumor tissue. Results indicated that even if the
      concentration of 5-FU and LV were reduced by half, these combined with CDDP were
      more effective than other therapies. Dual biochemical modulation therapy is
      particularly promising because the reduction of the dosages would reduce the side
      effects while still serving as an excellent anti-tumor therapy.

PMID- 8751803
TI  - [Administration method and recurrence-preventing effect of medroxyprogesterone
      acetate (MPA) as a postoperative adjuvant endocrine therapy for stage III breast
      cancer. Kitakyushu Collaborative Study Group for Breast Cancer].
AB  - By a collaborative study undertaken by 11 medical institutions in the Kita-Kyushu
      area, we evaluated the clinical efficacy of the combination of
      medroxyprogesterone acetate (MPA) and Tamoxifen (TAM) as a postoperative adjuvant
      endocrine therapy for Stage III breast cancer. First, 1 course of CAF therapy was
      administered; then, in combination with the basic therapy of 5-FU 200 mg/day p.
      o. for 3 years, ER (+) patients were treated with either 2-week sequential
      therapy of TAM (30 mg/day) and MPA (800 mg/day) or TAM (30 mg/day), and ER (-)
      patients received either MPA (800 mg/day) or 5-FU alone. Neither survival nor
      disease-free rates of the 92 analyzable patients were different between these
      treatment groups. Furthermore, the blood levels of MPA and cortisol had no
      correlation with survival and disease-free periods. We studied the effect of MPA
      on the natural inhibitors of blood coagulation, but found no difference from the
      result in healthy adults. It was, however, shown that MPA had a bone marrow
      protecting effect.

PMID- 8751805
TI  - [Investigation of retention time of intravesical instillation therapy with
      pirarubicin (THP)].
AB  - The effective and less side effect retention time of intravesical instillation
      therapy with Pirarubicin (THP) was investigated for the treatment of urinary
      bladder tumor. Fifty-seven cases of urinary bladder tumor were treated by
      intravesical instillation therapy with THP (20 mg/40 ml) a total of 6 times, with
      the first instillation at the time of surgery and the other 5 at a rate of three
      times a week thereafter. The retention time was 30 minutes, and it was allowed to
      last 10 or 60 minutes for comparison in some cases. Tumor and normal tissue were
      examined in the first instillation, and normal tissue in the sixth instillation.
      Infiltration to the bladder wall of THP was observed under fluorescence
      microscopy. Although the amount of tumor uptake was larger than normal tissue in
      the first instillation, no satisfactory infiltration was obtained. Repeated
      administration of THP with the retention time of 30 minutes enhanced the uptake
      and increased the infiltration in many cases, and side effects were scarcely
      noted. Retention time of 10 minutes was unsatisfactory, while the retention time
      of 60 minutes was discontinued in the early stage of treatment due to severe
      irritative bladder symptoms. Therefore, a retention time of 30 minutes is
      adequate in the case of repeated administration of THP in a short period.

PMID- 8751804
TI  - [Comparative clinical study of adjuvant postoperative chemotherapy (5-FU,
      Tegafur, 5-FU + MMC) in curatively resected cases of gastric cancer. Study Group
      on 5-FU Oral Adjuvant Chemotherapy in Gastric Cancer].
AB  - A multi-center collaborative study was conducted in curatively resected gastric
      cancer patients at Stages II and III to compare oral 5-FU (Group A), oral Tegafur
      (Group B) and i.v. MMC + oral 5-FU (Group C). From May 1982 to April 1985, 1,012
      cases were enrolled at 55 institutions. Some 138 (13.8%) were excluded, and 874
      were analyzable. In the analysis of background factors, Group B had more cases
      with tumor of large diameter and advanced Stage. Adverse effects were relatively
      mild in all groups, and there was no problem in drug tolerance. Five-year
      survival rate was 67.6%, 62.4% and 68.6% in Groups A, B and C, respectively,
      reflecting no significant difference among them. It was 85.0%, 83.0% and 81.1% in
      Stage II and 52.5%, 51.0% and 59.0% in Stage III of Groups A, B and C,
      respectively. No significant difference was found, but Stage III of Group C
      showed a slightly higher survival rate. Supportive clinical study will be
      required to assess the usefulness of MMC as an introduction therapy. We found no
      difference in efficacy between 5-FU and Tegafur as maintenance therapy. The life
      prolongation effect of fluoropyrimidines in comparison with surgery alone should
      be studied separately.

PMID- 8751806
TI  - [Comparative trial of granisetron alone and granisetron plus methylprednisolone
      for prevention of nausea and vomiting during cancer chemotherapy].
AB  - A crossover clinical trial between granisetron alone and granisetron combined
      with methylprednisolone (MPL) was undertaken for the prevention of nausea and
      vomiting during chemotherapy, including cisplatin, in 12 patients with advanced
      primary and metastatic lung cancer. The antiemetic effect was obtained in 91.7%
      (11/12 cases) of patients receiving granisetron alone compared to 100% (12/12
      cases) of patients receiving the combination of granisetron plus MPL. Complete
      control of anorexia was achieved in 91.6% (11/12 cases) of patients receiving the
      combination compared to 58.3% (7/12 cases) of patients receiving granisetron
      alone. Moreover there was a significant improvement of delayed clinical symptoms
      including nausea, vomiting, and anorexia in the patients receiving the
      combination of granisetron plus MPL. Our data suggest that the antiemetic effect
      of the combination of granisetron plus MPL is superior to granisetron alone in
      patients receiving cancer chemotherapy.

PMID- 8751807
TI  - [A case of recurrent breast cancer responding to long-term treatment with 5'-DFUR
      combined with MPA].
AB  - A 55-year-old woman with recurrent breast cancer treated with sequential
      mastectomies, chemo-and hormonal therapy of UFT, CPM and TAM, achieved remission.
      Six months later she was admitted with a diagnosis of carcinomatous pleurisy. A
      large pleural effusion was drained followed by administration of ADM, which
      improved her effusion and accompanying dyspnea. The effusion recurred but the
      patient desired outpatient treatment. Thus, we prescribed oral 5'-DFUR and MPA.
      One month later, her cough had improved and her sputum cytology was negative,
      while on chest radiograph the pleural effusion had decreased and the patch-like
      shadows in her right lung field had disappeared. She was considered as a case of
      PR. At one year and 3 months after starting concomitant 5'-DFUR and MPA the
      pleural effusion disappeared. The patient has received this outpatient treatment
      for 2 years without adverse reactions.

PMID- 8751808
TI  - [An elderly case of squamous cell lung cancer showing partial response by daily
      administration of oral etoposide].
AB  - We report an elderly case of squamous cell lung cancer showing partial response
      by daily administration of oral etoposide. The 86-year-old man had been diagnosed
      as squamous cell lung cancer (Stage II, T2N1M0) in September 1992. He had
      received no active treatment, because he was too old and had pulmonary emphysema.
      Dyspnea became gradually worse due to complete atelectasis of right lung in
      December 1994. After treatment with oral etoposide (50 mg/day) for 10 days,
      atelectasis was reduced and a partial response was obtained. No severe side
      effect except leukopenia was noted.

PMID- 8751809
TI  - [Biliary and pancreatic excretion of etoposide].
AB  - Although biliary excretion of Etoposide is thought to be one of the main
      excretory routes, less investigation has been performed in human because of the
      clinical difficulties of bile collection. In the present study, the biliary and
      pancreatic excretion of Etoposide was examined through the hepaticus- or
      pancreaticus drainage in two pancreatoduodenectomized patients. The drug (95 mg)
      was infused for 30 min. Blood, bile and pancreatic juice were taken consecutively
      during and after infusion. Etoposide in the samples was measured as an unchanged
      type by HPLC. Etoposide was detected in the bile at the same level or more of the
      blood, their correlation being significant during the observation period.
      Recovery of the unchanged drug from the hepatic bile in the present series was
      2.7-3.0% during the period of 3.5 hrs. And total recovery was estimated as 3.5
      4.0% from AUC of the further extended concentration curve. Pancreatic excretion
      of Etoposide was minimum, its ratio with blood concentration being 2-3%. Recovery
      for 3.5 hrs. was less than 0.02%. From the data obtained, the biliary excretion
      of Etoposide was discussed together with its metabolites.

PMID- 8751810
TI  - [A case of AFP (alpha-fetoprotein) producing gastric cancer successfully treated
      with FEP (5-FU, Epirubicin, cisplatin) therapy by continuous venous daily
      infusion of 5-FU and low-dose CDDP].
AB  - We reported our experience with a case of AFP producing gastric cancer with liver
      metastasis successfully treated with FEP therapy by continuous daily venous
      infusion of 5-FU and low-dose CDDP. A 59-year-old male was diagnosed with liver
      metastasis 2 months after partial gastrectomy of gastric cancer and then
      admitted. The patient received five courses of 24-hour continuous infusion of
      CDDP (5 mg/day, on day 1, 2, 3, 4, 5) and 5-FU (250 mg/day, on day 1, 3, 5) and
      bolus infusion of Epirubicin (10 mg/day, on day 3). No remarkable side effect was
      encountered. Complete response at the liver metastasis was observed by CT scan.
      Serum AFP level was down from 614 ng/ml to the normal range of 0.5 ng/ml after
      the therapy. The patient has been well for 10 months with complete remission.

PMID- 8751811
TI  - [A case of hepatocellular carcinoma treated by intra-arterial infusion
      chemotherapy using THP-adriamycin].
AB  - A 46-year-old male with unresectable hepatocellular carcinoma (HCC) comprised of
      severe liver dysfunction was treated by intra-arterial infusion chemotherapy
      through an implantable reservoir. During 39 months, a total amount of THP-ADR 420
      mg, ADR 70 mg and CDDP 350 mg was infused. Through the therapy, the tumor size on
      the lateral segment was well controlled, and serum AFP and PIVKA-II levels were
      also lowered. No severe side effect was observed. The patient was treated on an
      outpatient basis, and a good quality of life during therapy was maintained. This
      case suggests that THP-ADR may play an important role in a combined intraarterial
      chemotherapy for advanced HCC.

PMID- 8751812
TI  - [A case of recurrent multiple HCC after surgical resection showing regression by
      two TAEs using 5-FU and zinostatin stimalamer].
AB  - A-68-year-old man had hepatocellular carcinoma (HCC) in the area of S6 segment
      which was resected surgically. Three months after surgery, multiple recurrent
      lesions were found in both lobes of the liver. A transcatheter arterial
      embolization (TAE) with 5-FU and zinostatin stimalamer (SMANCS) was done. After
      TAE, the tumor mass disappeared in the right lobe and reduced to 10% in the left
      lobe. Although mass lesions remained unchanged for 3 months, the increased of AFP
      (143.9 ng/ml) was noticed after 4 months. Ten months after the second TAE with 5
      FU and SMANCS, the disappearance of tumor masses was confirmed by diagnostic
      images.

PMID- 8751813
TI  - [Successful treatment of recurrent endometrial stromal sarcoma by radiotherapy
      and intra-arterial chemotherapy with CDDP and ADM].
AB  - Endometrial stromal sarcoma (ESS) is a rare uterine malignancy. We describe a
      case of an ESS recurrence arising near a stump after hysterectomy. The 47-year
      old patient had the operation at another hospital because of myoma uteri as a
      preoperative diagnosis. Since the postoperative pathological diagnosis was ESS,
      CYVADIC was administered as adjuvant chemotherapy. But 3 years later, an isolated
      recurrent tumor was found locally near a stump in the pelvis. The patient
      underwent a combination of an intra-arterial chemotherapy and radiotherapy.
      Cisplatin and Adriamycin was administered in 20 mg/m2 everyday for 5 days and 60
      mg for 1 day, respectively. On the other hand, the tumor irradiation dose was 50
      Gy for 5 weeks. After this combination therapy, the recurrent tumor size grew
      smaller on CT. This result suggests that the combination of intra-arterial
      administration of cisplatin and Adriamycin, and radiation is an effective therapy
      for a localized recurrent tumor of ESS.

PMID- 8751814
TI  - [A case of alpha-fetoprotein producing mediastinal germ cell tumor treated with
      preoperative chemotherapy].
AB  - A 20-year-old male was treated with 3 courses of cisplatin combined chemotherapy,
      with a clinical diagnosis of mediastinal germ cell tumor. Although alpha
      fetoprotein (AFP), which alone had been high (893 ng/ml on admission) among tumor
      markers examined, normalized after chemotherapy, the size of the tumor remained
      unchanged. The patient underwent total resection of the tumor and has been
      followed with no evidence of recurrence for 18 months. Pathological examination
      suggested that the tumor was an immature teratoma with extensive proliferation of
      fibrous element. Neither other elements of germ cell tumor nor AFP producing
      cells were found. Preoperative chemotherapy is usually effective in treatment of
      germ cell tumors. However, it is important to recall that measurements of tumor
      volume occasionally do not provide information on the tumor's response.

PMID- 8751815
TI  - [Immunohistochemical localization of thymidine phosphorylase in primary lung
      cancer].

PMID- 8751816
TI  - Application of structural concepts to evaluate the potential carcinogenicity of
      natural products.
AB  - The expert structure-activity relational system CASE/MULTICASE was used to obtain
      an assessment of the possible carcinogenicity of selligueain A, a plant-derived
      sweetener. Based upon a series of authoritative data bases it was predicted that
      this chemical had some marginal potential for being a 'non-genotoxic' rodent
      carcinogen. The relevance of this potential to possible human health risks is
      problematic. Still, given the fact that successful sweetener may be widely
      consumed, should this chemical be developed further, experimental determinations
      of its potential carcinogenicity appear in order.

PMID- 8751818
TI  - Comparison of structure-activity relationships derived from two methods for
      estimating octanol-water partition coefficients.
AB  - This study examines several established linear relationships between 96-hour
      acute toxicity to fish (as log LC50) and octanol-water partition coefficient (as
      log Kow) with regard to the effect of using a different method of calculating log
      Kow. For all seven classes of compounds examined here, the linear equation
      parameters, viz., slope, intercept, r2, and standard error of the estimated log
      LC50, were about the same for the two methods. As expected, the accuracies of
      predictions for individual compounds were often different for the two methods,
      but seldom remarkably so.

PMID- 8751817
TI  - A novel QSAR approach for estimating toxicity of phenols.
AB  - Toxicity values (log IGC50(-1)) for 60 phenols tested in the 2-d static
      population growth inhibition assay with the ciliate Tetrahymena pyriformis were
      tabulated. Each chemical was selected so the series formed uniform coverage of
      the hydrophobicity/ionization surface. A high quality hydrophobicity-dependent
      (log Kow) structure-toxicity relationship (log IGC50(-1) = 0.741 (log Kow)-1.433;
      n = 17; r2 = 0.970; s = 0.134; F = 486.55; Pr > F = 0.0001) was developed for
      phenols with pKa values > 9.8. Similarly, separate hydrophobicity-dependent
      relationships were developed for phenols with pKa values of 4.0, 5.1, 6.3, 7.5,
      and 8.7. Comparisons of intercepts and slopes, respectively, revealed phenols
      with pKa values of 6.3 to be the most toxic and the least influenced by
      hydrophobicity. These relationships were reversed for the more acidic and basic
      phenols. Plots of toxicity versus pKa for nitro-substituted phenols and phenols
      with log Kow values of either 1.75 or 2.50 further demonstrated bilinearity
      between toxicity and ionization. In an effort to more accurately model the
      relationship between toxicity and ionization, the absolute value function [6.3
      pKa] was used to model ionization affects for derivatives with pKa values between
      0 and 9.8. For derivatives with pKa value > 9.8, a value of 3.50 was used to
      quantitate ionization effects. The use of log Kow in conjunction with this
      modified pKa (delta pKa) resulted in the structure-toxicity relationship (log
      IGC(50)-1 = 0.567 (log Kow)-0.226 (delta pKa)-0.079; n = 54; r2 = 0.926; s =
      0.215; F = 321.06; Pr > F = 0.0001). Derivatives with a nitro group in the 4
      position typically did not model well with the above equation.

PMID- 8751819
TI  - Attentional persistence for features of hierarchical patterns.
AB  - Priming for perceptual wholes and parts was examined in 4 experiments involving
      patterns arranged in a spatial hierarchy (D. Navon, 1977). Previous studies have
      demonstrated "level-specific priming" across successive trials for these patterns
      (L. C. Robertson, R. Egly, M. R. Lamb, & L. Kerth, 1993; L. M. Ward, 1982), and
      studies in neuropsychology have shown an absence of this priming effect in
      patient groups with parietal damage (R. Rafal & L. C. Robertson, 1994). The
      present experiments demonstrate that level-specific priming is linked to the
      spatial frequency differences between global and local forms in hierarchical
      patterns. They also show that level-specific priming is present even when the
      stimulus as a whole changes location. The effects last for up to 3 s without
      diminution and are not affected by changes in color, polarity, or contrast. These
      findings are discussed as they relate to spatial attention, object perception,
      and memory.

PMID- 8751820
TI  - Self-knowledge of an amnesic patient: toward a neuropsychology of personality and
      social psychology.
AB  - The authors present the case of W.J., who, as a result of a head injury,
      temporarily lost access to her episodic memory. W.J. was asked both during her
      amnesia and following its resolution to make trait judgments about herself.
      Because her responses when she could access episodic memories were consistent
      with her responses when she could not, the authors conclude that the loss of
      episodic memory did not greatly affect the availability of her trait self
      knowledge. The authors discuss how neuropsychological evidence can contribute to
      theorizing about personality and social processes.

PMID- 8751821
TI  - Seasonal study of the fungal biota of the fur of dogs.
AB  - During a one year period, 944 dogs from the Municipal kennel of Barcelona were
      examined to detect animals with suspected dermatophytosis. Only a few animals
      (1.8%) presented skin lesions but none of them had dermatophytosis. A
      representative number of dogs without visible skin lesions (n = 172), selected at
      random, were used to carry out a seasonal study of the mycobiota of their fur.
      Fifteen isolates belonging to the genera Microsporum and Trichophyton were
      isolated from 14 of the 172 (8.1%) dogs without lesions. The identity of these
      fungi was Microsporum gypseum (6/15), Trichophyton terrestre (4/15), M. canis
      (2/15), M. cookei (2/15) and Trichophyton ajelloi (1/15) (one strain each of M.
      gypseum and T. ajelloi were isolated from one dog). Species of Penicillium (%
      prevalence = 89.5%), Alternaria (86.6%), Cladosporium (84.9%), Aspergillus
      (77.3%), Scopulariopsis (65.7%) and Chrysosporium (64.5%) were the most
      prevalent. No significant differences in the fungal biota were observed with
      respect to age, gender, hair length or between mixed and pure breed dogs. A large
      number of isolates, including species belonging to the genera Beauveria,
      Chrysosporium, Malbranchea and Scopulariopsis, that macroscopically and/or
      microscopically resemble dermatophytes and may be mistaken for them, produced a
      red color change in Dermatophyte Test Medium. No significant seasonal difference
      was detected among the isolates belonging to the most frequently encountered
      genera, with the exception of Scopulariopsis (higher in summer and autumn) and
      Chrysosporium (higher in summer). Species from other genera, with lower
      occurrence also presented significant differences in their seasonal distribution.
      Arthrinium, Aureobasidium, Chaetomium and Phoma spp. presented maximum prevalence
      peaks in spring, Fusarium, Paecilomyces, Phoma and Rhizopus spp. in summer and
      Geotrichum and Mucor spp. in autumn. The Microsporum and Trichophyton species
      were more frequently isolated in summer.

PMID- 8751822
TI  - A study of dermatophytoses in Hamadan, the governmentship of West Iran.
AB  - In order to determine the extent and causative agents of dermatophytoses in the
      Hamadan region of West Iran; a study was made during a 9-month period from
      October 1991 to June 1992. A total of 7495 individuals were studied of whom 681
      (9%) were suspect of having cutaneous mycoses. Among them dermatophytoses were
      the commonest infections (259/681 = 38%). Of 259 individuals infected with
      dermatophytes, tinea capitis were observed in 163 (62.9%); t. corporis in 27
      (10.4%); t. manuum and t. cruris in 19 (7.3%) each; t. barbae and faciei in 14
      (5.4%); t. pedis in 13 (5%) and t. unguium in 4 (1.5%). A total of 144 patients
      yielded dermatophyte cultures. The frequency of the isolated species in
      decreasing order was as follows: Trichophyton verrucosum, 78 (54.1%); T.
      schoenleinii, 48 (33.3%); Microsporum canis, 8 (5.5%); Epidermophyton floccosum,
      5 (3.5%); T. mentagrophytes and M. gypseum, 2 (1.4%) each; T. tonsurans, 1
      (0.7%). In conclusion, the most prevalent dermatophytosis in this region was t.
      capitis with the infecting agent of T. schoenleinii.

PMID- 8751823
TI  - Acute effect of aflatoxin B1 on different inbred mouse strains II.
AB  - The acute effects of Aflatoxin B1(AFB1) were evaluated on C57B1/6, CBA/J, and
      Balb/c mice challenged with a single intraperitoneal dose of the mycotoxin (60
      mg/Kg animal weight). 90 mice per strain were divided into three groups of 30
      animals each: the intoxicated group and control groups I and II. Intoxicated mice
      were injected intraperitoneally with AFB1 dissolved in corn oil, while control I
      mice received corn oil only (0.01 ml/g) by the same route. Lots of 10 animals
      from the intoxicated and control groups were sacrificed 24, 72 and 168 hours
      after challenge. Control mice II remained untreated and were used as standards of
      normality for biochemical (hepatic and renal function) and hematological
      evaluation. AFB1 was detected in the liver of C57B1/6 and CBA/J mice 24 hours
      (1.46 and 0.75 ng/g, respectively), 72 hours (2.30 and 0.08 ng/g, respectively),
      and 168 hours (2.18 and 0.25 ng/g, respectively) after challenge. The mycotoxin
      was also observed in the liver of B10A mice (6.20 ng/g) 72 hours post-injection.
      The most evident histological lesions were observed 168 hours after treatment in
      C57B1/6 and B10A mice. Serum levels of alkaline phosphatase in intoxicated
      C57B1/6 and B10A mice were significantly higher than those of control I and II
      animals. The histopathologic lesions and biochemical changes were very discrete
      in Balb/c and CBA/J mice. It is included that strains C57B1/6 and B10A are more
      susceptible than strains CBA/J and Balb/c to the acute effects of AFB1. Such
      difference probably reflects each strain's ability to biotransform and eliminate
      AFB1 and its metabolites.

PMID- 8751824
TI  - Cryptococcosis as an opportunistic infection in immunodeficiency secondary to
      paracoccidioidomycosis.
AB  - We describe the case reports of two patients with immunodeficiency secondary to
      paracoccidioidomycosis (PCM) and opportunistic Cryptococcus neoformans
      infections. Secondary immunodeficiency likely occurred as a consequence of the
      intestinal loss of proteins and lymphocytes associated with malabsorption
      syndrome due to obstructed lymphatic drainage. Both patients had had severe
      abdominal involvement during the acute PCM disease. Immunological evaluation
      showed cellular and humoral immunity impairment. Cryptococcosis manifested as
      relatively well circumscribed lesions: osteolytic lesions of the skull in one
      patient, and pulmonary nodules in the other. The latter was treated surgically
      and with amphotericin B, whereas the other was treated with the combination
      amphotericin-B and flucytosine. Both patients had a good response to treatment
      with complete regression of the lesions. They have now 2 and 4 years of follow-up
      with maintenance therapy and no indication of reactivation of the infection. PCM
      also did not reactivate. The clinical and immunological characteristics of these
      patients are discussed and compared to the opportunistic C. neoformans infections
      of AIDS and transplant patients.

PMID- 8751825
TI  - Study of the role of iron in the anticryptococcal activity of human serum and
      fluconazole.
AB  - Anticryptococcal activity of human serum and apotransferrin in RPMI 1640 was
      studied in vitro. The effects of varying concentrations of FeCl3 on this activity
      was investigated. Possible synergy of serum and apotransferrin with fluconazole
      was also measured. The fungistatic activity of human serum, whether lyophilized,
      stored at 4 degrees C, fresh frozen or purchased from commercial sources vs.
      Cryptococcus neoformans was comparable. There was no significant loss of
      fungistatic activity after freezing and thawing the serum up to 10 times. The
      fungistatic activity of human serum was similar when tested in different tissue
      culture media with the exception of Medium 199. The addition of apotransferrin
      (2.0 or 0.2 mg/ml) to RPMI 1640 had an inhibitory effect on cryptococcal growth.
      This effect was reversed by 20 microM, of FeCl3 at both apotransferrin
      concentrations. By contrast, addition of FeCl3 to human serum and RPMI 1640 did
      not reverse inhibition of growth. Fluconazole synergized with the human serum
      preparations described, but not with pooled commercial serum, for fungicidal
      activity. Synergistic activity of fluconazole and human serum was not affected by
      the addition of FeCl3. Apotransferrin did not show any synergistic fungicidal
      activity with fluconazole.

PMID- 8751826
TI  - Isolation of opportunistic fungi from bronchoalveolar lavage of compromised hosts
      in Isfahan, Iran.
AB  - In this study, bronchoalveolar lavage (BAL) specimens from 247 immunocompromised
      patients were investigated for the incidence of opportunistic fungi. In the
      direct examination and culture of the specimens, 5 (2.02%) of filamentous fungi
      and 55 (22.26%) yeasts were isolated and identified as follows: Aspergillus
      fumigatus (2), A. terreus (1), A. nidulans (1), Mucor sp. (1), Candida albicans
      (29), C. glabrata (3), C. Parapsilosis (1), Trichosporon beigelii (1), Candida
      sp. (13) and unknown yeasts (8). In addition, one strain of Nocardia asteroides
      and two strains of Streptomyces sp. were isolated.

PMID- 8751827
TI  - Bovine mastitis due to algae of the genus Prototheca.
AB  - Protothecosis was described in many animals, with bovine mastitis being the main
      form. The increasing number of isolations of Prototheca spp. from bovine mastitis
      cases indicates the need of a detailed evaluation of this problem. Besides this,
      these algae do not respond to treatment with the antimicrobians most frequently
      applied, leading to elimination of the affected animals, as the best method to
      control the disease. In two dairy farms in the State of Sao Paulo, Brazil, a
      total of 155 lactating cows and 52 dry cows were examined. Milk samples were
      aseptically collected from lactating cows with clinical or subclinical mastitis.
      From dry cows, secretion samples from all quarters were collected. All samples
      were then taken to microbiological exams. At dairy farm 1, Prototheca spp. was
      isolated from 14.95% milk samples from lactating cows, (all of them cases of
      subclinical mastitis), and from 8.06% samples from dry cows. At dairy farm 2,
      Prototheca spp. was isolated from 5.1% milk samples and there were ten cases of
      clinical mastitis due to this agent. Although clinical mastitis has been
      considered the main form of occurrence of this pathology until now, it is
      important to consider Prototheca spp. as subclinical mastitis pathogen.
      Prototheca zopfii was the main specie isolated. In this study a high rate of
      intramammarian infections, as clinical or subclinical mastitis during lactation
      as well as in dry period, was observed, high lighting the importance of suitable
      diagnosis, so that control and preventive measures can be implemented to avoid
      dissemination of the agent.

PMID- 8751828
TI  - Candida albicans stress mannoproteins expression in superficial and systemic
      candidiasis. Stress mannoproteins in Candida albicans.
AB  - The presence of heat shock mannoproteins (HSMPs) reactive with sIgA was
      demonstrated in several C. albicans strains. The subculture of the C. albicans
      isolated from mucosal surfaces on Sabouraud's dextrose agar at 25 degrees C
      switched off the HSMP expression. A re-expression of the HSMPs was obtained in
      the same medium by shifting the temperature of incubation to 37 degrees C.
      However, expression of HSMPs in two strains isolated from deep infections was
      maintained during several subcultures on Sabouraud's dextrose agar at 25 degrees
      C. A glycoprotein of 200 kDa seemed to be the main HSMP reacting with vaginal
      sIgA. The data presented in this study suggest that factors other than
      temperature can influence the expression of C. albicans HSMPs and therefore these
      antigens should be referred as stress mannoproteins.

PMID- 8751829
TI  - Development of an L6 myoblast in vitro model of moniliformin toxicosis.
AB  - L6 myoblasts were used as an in vitro model to investigate the role of
      moniliformin and its interaction with monensin in turkey knockdown syndrome and
      sudden death syndromes in poultry. Cell viability and microscopic and
      ultrastructural alterations noted in L6 myoblasts cultured in the presence of
      moniliformin (0.0-0.3 microgram/microliter) were compared to those observed in
      parallel cultures also containing one of the following compounds: selenium (0
      0.004 ng/microliter), thiamine (0-0.3 microgram/microliter), or pyruvate (0-0.46
      microgram/microliter). Marked dilation of the RER, membranous whorls, glycogen
      deposition, membrane-bound cytoplasmic inclusions and necrosis were observed in
      myoblasts exposed to 0.03-0.30 microgram moniliformin/microliter medium.
      Supplementation of medium with thiamine and pyruvate, or selenium, provided
      significant protection to cells exposed to 0.0-0.3 microgram/microliter or 0.0
      0.15 microgram moniliformin/microliter, respectively. Dose-dependent differences
      in protein and ATP production were not detected. Myoblasts grown in medium
      containing 0-0.15 microgram moniliformin/microliter and 7.5-50.0 microM A23187,
      beauvericin or monensin had degrees of cytotoxicity similar to parallel cultures
      receiving only an ionophore. L6 myoblasts were a useful model of moniliformin
      toxicosis. The findings of this study suggest cytotoxicity due to moniliformin in
      L6 myoblasts may be due in part to oxidative damage and altered pyruvate
      metabolism, and that moniliformin does not predispose myoblasts to ionophore
      toxicosis. This study supports the results of in vivo investigations in poultry
      that moniliformin and monensin do not act synergistically to induce knockdown or
      monensin toxicosis.

PMID- 8751830
TI  - Purified moniliformin does not affect the force or rate of contraction of
      isolated guinea pig atria.
AB  - Chronic exposure to moniliformin results in the development of myocardial
      hypertrophy and degeneration. The cause of this hypertrophy is unknown. However,
      moniliformin-induced hypoxia or altered function of cardiac pyruvate
      dehydrogenase, rather than direct cardiostimulation have been proposed as
      potential mechanisms. Isolated guinea pig atria were used in a cumulative
      concentration-response model to evaluate the direct effect of moniliformin on the
      rate and force of atrial contraction. Moniliformin did not affect the rate or
      force of atrial contraction. These results are consistent with the hypothesis
      that moniliformin does not have a cardiostimulatory effect. Therefore cardiac
      stimulation. e.g. stimulation of beta-adrenergic receptors, is unlikely to be the
      cause of the myocardial hypertrophy observed in poultry chronically intoxicated
      with moniliformin.

PMID- 8751831
TI  - Absence of detectable fumonisins in the milk of cows fed Fusarium proliferatum
      (Matsushima) Nirenberg culture material.
AB  - Fumonisins, a group of mycotoxins produced by the ubiquitous fungi Fusarium
      moniliforme and F. proliferatum, were first identified about eight years ago.
      They have been shown to cause a variety of health effects in animals, including
      epidemiological evidence of esophageal cancer in humans. Cattle are less
      sensitive to ill effects than horses and swine. Fumonisins are common
      contaminants of low quality grain fed to cattle. Culture material containing
      fumonisins (FB1, FB2, and FB3) was mixed into the total diet and fed for 14 days
      to two midlactation Jersey cows to determine if fumonisins are excreted in milk.
      The dietary equivalent of fumonisin was approximately 75 ppm and the two cows
      consumed an average of 3 mg fumonisin B1/kg body weight (bwt)/day. Fumonisins
      were not detected in any of the milk samples by two analytical laboratories using
      methods with a sensitivity of 5 ng/ml. Except for transient diarrhea at the
      beginning of the contaminant feeding period and an increase in serum cholesterol,
      clinical and hematologic changes were not observed in the animals. The appearance
      or carry over of fumonisins from feed to milk in dairy cows does not appear to be
      significant and likely not a hazard or food safety concern for humans.

PMID- 8751832
TI  - Differential inhibition of IL-1 alpha and TNF-alpha generation by ammonium
      metavanadate in murine macrophages.
AB  - The relationship between immunotoxicity of ammonium metavanadate (NH4VO3) and
      levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) was
      studied with a NH4VO3-treated murine macrophage-like cell line, 1774 and resident
      peritoneal macrophages (PEM) obtained from treated mice. Lipopolysaccharide (LPS)
      induced elevation of extracellular TNF-alpha in PEM and 1774 cells was not
      markedly affected by prior treatment with vanadate. However, PEM from treated
      mice at 10 mg V/kg (10V) had a significantly lower level of LPS-induced
      intracellular TNF-alpha. NH4VO3-treated 1774 cells at 3.6 (V1) and 7.2 micrograms
      V/10(7) cells (V2) had significantly higher levels of intracellular TNF-alpha
      than the PO4 and V3 (10.8 micrograms V/10(7) cells) groups. Although the four PEM
      groups showed no marked difference in extracellular IL-1 alpha levels, PEM from
      treated mice at 2.5V and 10V had significantly lower levels of intracellular IL-1
      alpha than those from control groups. 1774 cells from PO4 and NH4Cl groups showed
      significant increases in intracellular IL-1 alpha following treatment with LPS.
      However, 1774 cells with prior treatment with vanadate revealed significant
      reduction in levels of LPS-induced intracellular IL-1 alpha when compared to
      control groups. Therefore, the previously reported reduced resistance of vanadate
      treated mice to Listeria monocytogenes could be attributed to an inhibitory
      effect on the production of IL-1 alpha in macrophages.

PMID- 8751833
TI  - Effect of perchloroethylene and its metabolites on intercellular communication in
      clone 9 rat liver cells.
AB  - Gap junction intercellular communication (IC) is thought to be important in
      chemical carcinogenesis as abnormalities in IC have been found in cancer cells.
      Perchloroethylene (PERC) is metabolized in rodent liver to dichloroacetic acid
      (DCA) and trichloroacetic acid (TCA), which are rodent liver carcinogens. Chloral
      hydrate (CH) and trichloroethanol (TCEth) are kidney metabolites. We used Lucifer
      yellow scrape-load dye transfer as a measure of IC to look at the effect of PERC,
      DCA, TCA, CH, and TCEth on Clone 9 cell cultures (normal rat liver cells). Four
      independent experiments were performed for each chemical using exposure times of
      1, 4, 6, 24, 48, and 168 h. Concentrations for each chemical varied and were
      based on preliminary data on effect and cytotoxicity. To compare the relative
      effectiveness of each chemical to cause biological change, we identified the
      lowest concentration and shortest time to significantly reduce dye transfer. DCA
      caused a significant change at 10 mM at 6 h; TCA, 1 mM at 1 h; CH and TCEth, 1 mM
      at 24 h; and PERC, 0.01 mM at 48 h. Over a 24-h treatment period, the relative
      efficiencies, as defined by the concentration needed to produce 50% reduction in
      IC, were PERC (0.3 mM) >> TCA (3.8 mM) > TCEth (6.6 mM) = CH (7.0 mM) >> DCA (41
      mM). Time-course data indicated that PERC, DCA, and TCA produced reduction in IC
      in a similar fashion, but 5 mM CH or TCEth exhibited variances from these results
      and may indicate specific cell responses to these chemicals. The mechanism(s)
      responsible for inhibition of IC by these structurally related chemicals needs to
      be established.

PMID- 8751834
TI  - Repeated oral benzene exposure alters enzymes involved in benzene metabolism.
AB  - Benzene is a known carcinogen and hematopoietic toxin in humans and experimental
      animals. The effect of acute, high-dose exposure to benzene on hepatic
      bioactivation and detoxication enzymes has been defined, while little is known
      about the effect of repeated, low-dose benzene exposure on these enzymes. Our
      objective was to determine whether repeated, oral benzene exposure alters enzymes
      involved in benzene metabolism. Specifically, we were concerned with cytochrome P
      450-2E1, a bioactivation enzyme, and glutathione transferase and aldehyde
      dehydrogenase, two detoxifying enzymes. Female CD-1 mice were treated by gavage
      for 3 wk with benzene doses of 5 mg/kg (0.064 mmol/kg) or 50 mg/kg (0.646
      mmol/kg) in corn oil. These doses of benzene produced 0.048 and 0.236 mumol
      muconic acid/d, respectively. We found that repeated exposure to 50 mg
      benzene/kg/d decreased P-450-2E1 activity by 34% and induced glutathione
      transferase activity by 30% without affecting aldehyde dehydrogenase activity.
      These changes in enzyme activities may serve a protective role against repeated
      exposure to benzene.

PMID- 8751835
TI  - Measurement of the urinary benzene metabolite trans,trans-muconic acid from
      benzene exposure in humans.
AB  - The concentration of the urinary benzene metabolite trans, trans-muconic acid was
      measured after exposure to benzene contained in environmental tobacco smoke
      (ETS). Volunteers were exposed to environmental tobacco smoke at different
      exposure levels and for different exposure durations. Urine samples were
      collected preexposure and postexposure for 24 h on exposure days. To determine
      background levels, urine samples were also collected on three individual days
      when no exposure to ETS occurred. Urinary muconic acid was elevated following
      benzene exposure in ETS compared to an individual's background level and can be a
      useful biomarker in control, characterized studies of sub-parts-per-million (sub
      ppm) benzene exposures. However, the use of muconic acid as a bio-marker of
      benzene exposure at sub-ppm levels in the general population is problematic
      because of variability in the time between exposure and excretion and in an
      individual's background excretion rate. Urinary muconic acid associated with
      benzene in ETS exposure was excreted within 12 h of the exposure. A higher
      proportion of the benzene dose following environmental exposure in the sub-ppm
      range was excreted as urinary muconic acid (mean of 25%, range 7.2-58%) than
      found in either animal or occupational studies at higher benzene doses. The
      higher proportion of benzene excretion as urinary muconic acid at low benzene
      exposure indicates that the relationship between exposure and metabolism by the
      ring opening pathway is nonlinear in humans, and extrapolation from high doses to
      environmental benzene exposure potentially underestimates health risks mediated
      by the ring opening metabolic pathway that produces muconic acid, as has been
      suggested by previous animal data.

PMID- 8751836
TI  - Urinary chromium concentrations in humans following ingestion of safe doses of
      hexavalent and trivalent chromium: implications for biomonitoring.
AB  - In this study, we evaluate the significance of increased urinary chromium
      concentrations as a marker of chromium exposure and potential health risk. Six
      human volunteers ingested trivalent chromium [Cr(III)] and hexavalent chromium
      [Cr(VI)] at doses that are known to be safe but are much higher than typical
      dietary levels. The following dosing regimen was used: d 1-7, 200 micrograms/d
      chromium picolinate (a dietary supplement); d 8-10, Cr(VI) ingestion at the U.S.
      Environmental Protection Agency (EPA) reference dose (RfD) of 0.005 mg/kg/d; d 11
      13, no dose; d 14-16, Cr(III) ingestion at the U.S. EPA RfD of 1.0 mg/ kg/d; and
      d 17-18, postdose. Urine voids were collected throughout the dosing periods and
      analyzed for chromium. Our findings are as follows: (1) ingestion of 200
      micrograms/d of chromium picolinate yielded significantly elevated urine
      concentrations such that each participant routinely exceeded background, (2)
      ingestion of the Cr(VI) RfD (0.005 mg/kg/d) yielded individual mean urinary
      chromium levels (1.2-23 micrograms/L) and a pooled mean urinary chromium level
      (2.4 micrograms/L) that significantly exceeded background, and (3) ingestion of
      the Cr(III) RfD yielded no significant increase in urinary chromium
      concentrations, indicating that little, if any, absorption occurred. Our work
      identified three critical issues that need to be accounted for in any future
      studies that will use urinary chromium as a marker of exposure. First, a minimum
      urinary chromium concentration of approximately 2 micrograms/L should be used as
      a screening level to critically identify individuals who may have experienced
      elevated exposures to chromium. Second, if Cr(III) levels in soils are known to
      be less than 80,000 ppm and the Cr(III) is insoluble, urinary chromium
      concentrations are not an appropriate marker of exposure. Third, newer forms of
      chromium supplements that contain organic forms of Cr(III) must be considered
      potential confounders and their contribution to residential chromium uptake must
      be carefully evaluated.

PMID- 8751837
TI  - Pulmonary microsomal metabolism of benzo[a]pyrene following exposure of rats to
      silica.
AB  - Because some evidence suggests that there may be an increased incidence of lung
      cancer in silicosis and because previous studies have shown that exposure of rats
      to silica alters the pulmonary cytochrome P-450 system, we studied the effects of
      exposing rats to silica on the lung microsomal metabolism of benzo[a]pyrene
      (BaP). Rats were exposed to silica by intratracheal administration, lung
      microsomes were obtained 2 wk later from untreated and silica-treated animals,
      and the amounts of microsomal tissue and metabolites formed during the in vitro
      microsomal metabolism of BaP were measured. When the formation of BaP metabolites
      in equal amounts of lung microsomal tissue from the 2 treatment groups is
      compared, 3-OH BaP, BaP 4,5-diol, and BaP 9,10-diol are reduced by 45-70%, but
      the formation of BaP 7,8-diol or the BaP-quinones is not significantly altered
      following exposure to silica. In fact, the ratio of the BaP diols and BaP
      quinones, potentially toxic metabolites, to the relatively nontoxic 3-OH BaP
      produced by equal amounts of lung microsomal tissue is increased more than
      threefold following exposure of rats to silica. Since exposure of rats to silica
      leads to increased levels of lung microsomal protein, the amounts of BaP
      metabolites that could be produced by all microsomal tissue in the lungs were
      calculated. In silica-treated animals, the calculated total lung production of 3
      OH BaP, BaP 4,5-diol, and BaP 9,10-diol tends to be increased by 1.2- to 2.0
      fold, but BaP 7,8-diol and the BaP quinones are increased by 3.5-fold. These
      results demonstrate that exposure of rats to silica may alter the capacity of the
      lungs to metabolize benzo[a]pyrene, and the greatest effect seems to be enhanced
      accumulation of BaP 7,8-diol and the BaP quinones.

PMID- 8751838
TI  - Behavioral, neurochemical, and neuromorphological effects of deltamethrin in
      adult rats.
AB  - The neurotoxic action of a synthetic pyrethroid, a deltamethrin formulation
      (Decis), was studied in adult rats. Adult male albino rats received deltamethrin
      in formulation at a dose of 7.0 mg/kg body weight/d in corn oil orally for 15 d.
      Deltamethrin-exposed rats exhibited a decrease in body weight from d 9 onward,
      which was significantly lowered at d 15 of exposure. Administration of
      deltamethrin markedly increased the wet weight of the hippocampus and pons
      medulla region without much affecting the weight of frontal cortex, corpus
      striatum, hypothalamus, and cerebellum. A significant increase in the activity of
      monoamine oxidase was observed in frontal cortex, hippocampus, and cerebellum,
      and acetylcholinesterase activity was markedly increased in frontal cortex,
      corpus striatum, hippocampus, cerebellum, and pons medulla. The activity of
      Na+,K(+)-ATPase showed marked decrease in frontal cortex, hippocampus, and
      cerebellum following deltamethrin exposure. The polyamine concentration in brain
      regions was significantly affected, and all three polyamines showed marked
      alterations in the cerebellum. Deltamethrin significantly increased the
      spontaneous locomotor activity and aggressive behavior. Maze learning was
      markedly decreased. Morphological changes in Purkinje neurons in the cerebellum
      were observed in deltamethrin-exposed rats. Results suggest significant
      neurochemical and neuromorphological changes, which may culminate in perturbed
      synaptic function following deltamethrin exposure in rats.

PMID- 8751839
TI  - The state of the stent: current practices, controversies, and future trends.
AB  - Stent use has been increasing steadily over the last 5 years and might be viewed
      as the "second wind" of angioplasty. A large number of different stents are now
      available, and many trials have been designed to assess their safety and
      efficacy. But do comparisons of the various stents serve a useful purpose-i.e.,
      do they address real medical questions? Many issues remain unresolved, such as
      who should and should not be stented, what the actual costs are of this modality,
      and what the future holds in terms of multifunctional devices. In addition,
      research is under way to explore such areas as techniques for stent guidance, the
      role of anticoagulation and adjunctive therapies, treatment of patient subsets
      (e.g., those with ischemic syndromes or challenging coronary anatomy), and
      synergistic approaches (e.g., directional atherectomy, radiotherapy, laser
      angioplasty). The results of such studies are likely to change the face of
      interventional cardiology.

PMID- 8751840
TI  - Carotid stent-supported angioplasty: a neurovascular intervention to prevent
      stroke.
AB  - Obstructive carotid artery disease is responsible for 60% of strokes in the
      United States and is the third major cause of death. Stent-supported carotid
      artery angioplasty has the potential to prevent stroke in thousands of patients
      and offers a number of potential advantages over surgical revascularization
      (carotid endarterectomy). Results of the prospective observational study at the
      University of Alabama at Birmingham indicate that carotid stent-supported
      angioplasty is safe and probably effective in reducing stroke in patients with
      high-risk cerebrovascular disease. Technical success was achieved in 99% of 146
      procedures; 210 stents were placed in 152 vessels, with only 1 instance of stent
      thrombosis. The rate of major in-hospital complications was unexpectedly low-only
      1 death and 2 major strokes. Seven patients suffered minor strokes, but only 2
      were left with minor weakness. When compared with a projected complication rate
      of 6% had these patients undergone carotid endarterectomy, stenting resulted in
      fewer major events. At 6-month follow-up, 69 of 74 patients were evaluated by
      angiography or ultrasound, which detected 8 cases of stent deformation and a
      restenosis rate of < 5%. Because of these instances of stent deformation, use of
      the Palmaz (biliary) stent was discontinued. Although 1 patient had a transient
      ischemic attack, no strokes occurred during follow-up. To date, carotid stenting
      is an investigational procedure. Cardiovascular interventionalists, industry, and
      the FDA are encouraged to validate this approach through clinical testing.
      However, improvements in technique, devices, and adjunctive therapies are needed
      before the method can be tested in randomized trials.

PMID- 8751841
TI  - Subacute stent thrombosis and the anticoagulation controversy: changes in drug
      therapy, operator technique, and the impact of intravascular ultrasound.
AB  - Clinical trials have shown that stents are superior to other catheter-based
      coronary interventions in terms of reduced complications and improved long-term
      efficacy. With utilization of high-pressure balloon inflation and intravascular
      ultrasound (IVUS) guidance, stent implantation can now be performed safely
      without anticoagulation (i.e., with lower rates of stent thrombosis and vascular
      complications). In 2 recent prospective clinical trials, stent thrombosis
      occurred in 3.5% of cases despite anticoagulant therapy, which resulted in an
      average of 7% vascular and bleeding complications. Initial use of IVUS during
      traditional stent deployment showed that 80% of stents were underexpanded and led
      to the hypothesis that stent thrombosis might be decreased as a result of optimal
      stent placement under IVUS guidance without the need for anticoagulation. In a
      prospective clinical trial to test this hypothesis, three factors were found to
      reduce stent thrombosis: full stent expansion, complete apposition to the vessel
      wall, and full lesion coverage. Predictors of thrombotic risk in this era of high
      pressure stent deployment without anticoagulation include low ejection fraction,
      residual dissections, slow flow, multiple stents per lesion, and smaller
      postprocedure stent luminal diameter. To optimize stent expansion, stent dilation
      should be performed using a mean inflation pressure of 18 atm with a noncompliant
      or minimally compliant balloon sized to the vessel being treated (B/V ratio =
      1.1). Controversy still remains about the best poststent antiplatelet regimen,
      and results of a recent trial should indicate whether heparin coating provides
      additional protection from stent thrombosis.

PMID- 8751842
TI  - Intravascular ultrasound to discern device-specific effects and mechanisms of
      restenosis.
AB  - Restenosis continues to be the "Achilles heel" of transcatheter interventions.
      While attempts to reduce restenosis by inhibiting cellular proliferation through
      pharmacologic or mechanical means have been unsuccessful, stents, which inhibit
      acute recoil and chronic remodeling, have been shown convincingly to reduce
      restenosis in 2 randomized clinical trials. Intravascular ultrasound (IVUS)
      allows transmural, tomographic imaging of coronary arteries in humans in vivo to
      subdivide restenosis into the two basic underlying components: tissue
      proliferation and arterial remodeling. In studies performed at the Washington
      Hospital Center, in nonstented lesions 73% of late lumen loss was due to arterial
      remodeling (a decrease in arterial, or external elastic membrane cross-sectional
      area) and 27% was due to tissue growth (an increase in plaque plus media cross
      sectional area). These findings were confirmed by 2 other studies: the Optimal
      Atherectomy Restenosis Study (OARS) and the Serial Ultrasound analysis of
      REstenosis (SURE) Trial. IVUS was also used to study the mechanisms by which
      stents reduce restenosis. Stents created a larger final lumen cross-sectional
      area and, for all practical purposes, abolished arterial remodeling to offset a
      stent-related increase in neointimal tissue accumulation. Neointimal hyperplasia
      is solely responsible for in-stent restenosis and therefore appears to be a pure
      model for studying strategies to limit tissue proliferation.

PMID- 8751843
TI  - Local catheter-based intracoronary radiation therapy for restenosis.
AB  - Intracoronary radiation therapy was shown to be effective in limiting "restenosis
      like" phenomena by inhibiting neointima formation after balloon angioplasty in
      porcine coronary arteries. Using the same treatment doses, both gamma and beta
      emitters demonstrated similar results, despite differences in isotope
      characteristics (e.g., penetration, activity, dose rate, and treatment time). In
      addition, intracoronary radiation delivered via a catheter-based system prior to
      coronary stenting reduced neointimal hyperplasia in the porcine model and may
      further reduce restenosis when coupled with stent implantation. Radioactive
      stents are of value, especially in large vessels, because of their low activity
      and proximity to the vessel wall. Adventitial labeling and immunostaining have
      suggested that the mechanisms by which radiation reduces restenosis are (1)
      inhibition of smooth muscle cell proliferation in the adventitia and (2)
      favorable effects on vessel remodeling. Technical radiation considerations are
      also discussed, including isotope selection, treatment dose, homogeneous
      dosimetry, treatment time, and total body dose to the patient and healthcare
      personnel. New catheter-based delivery systems for intracoronary use are
      currently being developed and are described. Preliminary clinical and
      angiographic studies using endovascular radiation after balloon angioplasty in
      both stented and nonstented peripheral and coronary arteries indicate favorable
      long-term results. In response to the growing enthusiasm for this approach,
      larger populations must be studied to determine whether this new therapy will
      influence the restenosis rate and clinical events after angioplasty and, in a
      broader sense, the field of interventional cardiology.

PMID- 8751844
TI  - Aggressive intervention for myocardial infarction: angioplasty, stents, and intra
      aortic balloon pumping.
AB  - Primary percutaneous transluminal coronary angioplasty (PTCA) is not used in all
      hospitals capable of performing it because the data regarding results are either
      not known or not easily interpreted. Unlike pharmaceutical trials, which receive
      $30-50 million in research funds, virtually all trials of PTCA have been
      unfunded. Nevertheless, several groups have conclusively proved the benefit of
      primary PTCA over thrombolysis. In a 1995 meta-analysis, PTCA proved superior to
      thrombolytic therapy in reducing death and reinfarction. The Global Utilization
      of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries
      (GUSTO-IIB) substudy confirmed this fact with 94% certainly. Other studies were
      designed to refine the angioplasty technique. In the Primary Angioplasty in
      Myocardial Infarction (PAMI-I) study, acute catheterization was used to stratify
      patients and identified a low-risk population whose mortality equaled that of
      patients treated electively. Compared with clinical risk factors, angiographic
      findings enhanced the power to predict mortality three-fold. The high-risk subset
      with acute myocardial infarction (MI) was also randomized to treatment with or
      without prophylactic intra-aortic balloon pumping (IABP). Although IABP caused no
      complications, it had no positive effect on primary endpoints (death, recurrent
      MI, and reocclusion) and did not improve left ventricular function at 6 months.
      One limitation of primary PTCA is a high rate of late restenosis (30-50% at 6
      months). In a pilot study we are examining the role of stents in conjunction with
      primary PTCA. Early results indicate that in the 69% of patients eligible for
      stent placement, in-hospital events were uncommon (no deaths, no reinfarctions,
      low rate of recurrent ischemia) and the need for repeat revascularization was
      infrequent.

PMID- 8751845
TI  - Glycoprotein IIb/IIIa receptor inhibitors: putting the EPIC, IMPACT II, RESTORE,
      and EPILOG trials into perspective.
AB  - Clinical evaluation of the antiplatelet glycoprotein (GP) IIb/IIIa receptor
      antagonists has now extended over nearly a decade. The largest experience to date
      with this new class of agents has been in the prevention and management of
      complications of percutaneous coronary intervention. Four trials involving 3
      different agents in the setting of coronary intervention are discussed: the
      Evaluation of c7E3 in Preventing Ischemic Complications (EPIC) and the Evaluation
      of PTCA to Improve Long-term Outcome by c7E3 GPIIB/IIIA Receptor Blockade
      (EPILOG) trials of the antibody fragment abciximab (ReoPro); the Integrilin to
      Minimize Platelet Aggregation and Prevent Coronary Thrombosis II (IMPACT II)
      trial evaluating the peptide Intergrilin; and the Randomized Efficacy Study of
      Tirofiban for Outcomes and Restenosis (RESTORE) trial studying the nonpeptide
      mimetic tirofiban (Aggrastat). All 3 agents reduced the incidence of clinically
      relevant endpoint events but to differing degrees and for varying durations. The
      increased rates of bleeding complications seen in the EPIC trial appear to be
      lessened by the use of competitive GP IIb/IIIa inhibitors and by studious
      titration of heparin and careful groin management. The findings in IMPACT II and
      EPILOG suggest that the entire spectrum of patients who undergo coronary
      intervention benefit from GP IIb/IIIa blockade. Based on the results of these
      trials, platelet GP IIb/IIIa integrin blockade appears to be instrumental in
      improving clinical outcomes following percutaneous intervention, with clinical
      benefit extending to all patient categories. Bleeding risks can be minimized by
      minor changes in standard patient care algorithms. Dosing strategies and
      treatment duration still need to be refined, especially for the competitive
      antagonists. The role of these agents as adjuncts in stenting and rotational
      atherectomy and as adjunctive therapy in other disease settings requires further
      study.

PMID- 8751846
TI  - Evolution of the filmless cardiac angiography suite: promise and perils of the
      evolving digital era.
AB  - Although cineangiography has been in use for 35 years, it has important
      limitations. Films are expensive to produce, cannot be readily copied or
      transmitted electronically, are bulky, and require a large storage space. Digital
      angiography will soon replace film for archiving cardiac catheterization images,
      ultimately offering powerful new capabilities at a reduced cost. The transition
      toward the filmless angiogram is characterized by both great promise and
      important risks. Current nonfilm archiving systems (such as super-VHS videotape
      or analog optical disks) have not met the needs of the cardiovascular community,
      owing to poor image quality and resolution inferior to that of cine films. Analog
      storage media can result in a standard error in lesion measurements exceeding 1
      mm and have a suboptimal signal-to-noise ratio. While digital media record
      adequate image detail, proprietary formats preclude the universal compatibility
      supplied by cine film. As a consequence of incompatibility, referred patients
      must undergo repeat catheterization prior to surgery or intervention. To resolve
      the compatibility problem, a committee established by the American College of
      Cardiology in conjunction with manufacturers (DICOM) has developed a standardized
      digital recording format using CD-ROM to transfer images between medical centers.
      The availability of this standardized interchange medium will have a positive
      impact on research as well as on patient care by eliminating barriers to image
      exchange throughout the cardiovascular community. Support for the DICOM approach
      by practitioners is vital to the transition to digital future.

PMID- 8751847
TI  - The beta-particle-emitting radioisotope stent (isostent): animal studies and
      planned clinical trials.
AB  - Radiation delivered by intravascular stent is an appealing approach to prevent
      neointimal hyperplasia, since it nonselectively kills dividing cells. In
      particular, beta-particle-emitting radioisotope stents may prove to be an ideal
      means of local irradiation in that 95% of the dose is delivered within 4 mm of
      the stent edge and the dose drops off rapidly to < 1/1,000 of the original dose
      at 5 months postimplantation. In the in vitro smooth muscle cell model, one can
      observe a zone of growth inhibition around radioactive stent wires that averages
      about 6 mm at very-low-activity levels (0.006 microCi/cm of wire). In vivo
      studies in animal models, including porcine iliac and coronary arteries and
      rabbit iliac arteries, have shown the effectiveness of radioisotope stents in
      inhibiting neointimal proliferation. Proliferating endothelial cells appear to be
      relatively radioresistant. A computer model was employed to look at the radiation
      dose delivered as a function of distance from the stent. With very-low-activity
      stents, presumably, DNA of the smooth muscle cells is damaged as they migrate
      through the "electron fence" on the way to the neolumen, diminishing the
      population of myofibroblasts and reducing hyperplasia. Catheter-based radiation
      therapies may disable these cells before they migrate, although such an approach
      may not inhibit early recoil or late contraction. Based on the characteristics of
      beta emissions (i.e., rapid drop-off, minimal leaching), radioisotope stents
      containing phosphorus-32 appear to be safe. A randomized triple-blind clinical
      trial is planned to assess restenosis at 6 months in native coronary arteries
      treated with radioisotope stents.

PMID- 8751848
TI  - Mutational hot spots in the mitochondrial microcosm.

PMID- 8751849
TI  - The second National Research Council report on forensic DNA evidence.

PMID- 8751850
TI  - How rapidly does the human mitochondrial genome evolve?
AB  - The results of an empirical nucleotide-sequencing approach indicate that the
      evolution of the human mitochondrial noncoding D-loop is both more rapid and more
      complex than is revealed by standard phylogenetic approaches. The nucleotide
      sequence of the D-loop region of the mitochondrial genome was determined for 45
      members of a large matrilineal Leber hereditary optic neuropathy pedigree. Two
      germ-line mutations have arisen in members of one branch of the family, thereby
      leading to triplasmic descendants with three mitochondrial genotypes. Segregation
      toward the homoplasmic state can occur within a single generation in some of
      these descendants, a result that suggests rapid fixation of mitochondrial
      mutations as a result of developmental bottlenecking. However, slow segregation
      was observed in other offspring, and therefore no single or simple pattern of
      segregation can be generalized from the available data. Evidence for rare mtDNA
      recombination within the D-loop was obtained for one family member. In addition
      to these germ-line mutations, a somatic mutation was found in the D-loop of one
      family member. When this genealogical approach was applied to the nucleotide
      sequences of mitochondrial coding regions, the results again indicated a very
      rapid rate of evolution.

PMID- 8751852
TI  - Succinyl CoA: 3-oxoacid CoA transferase (SCOT): human cDNA cloning, human
      chromosomal mapping to 5p13, and mutation detection in a SCOT-deficient patient.
AB  - Succinyl CoA: 3-oxoacid CoA transferase (SCOT; E.C.2.8.3.5) mediates the rate
      determining step of ketolysis in extrahepatic tissues, the esterification of
      acetoacetate to CoA for use in energy production. Hereditary SCOT deficiency in
      humans causes episodes of severe ketoacidosis. We obtained human-heart SCOT cDNA
      clones spanning the entire 1,560-nt coding sequence. Sequence alignment of the
      human SCOT peptides with other known CoA transferases revealed several conserved
      regions of potential functional importance. A single approximately 3.2-kb SCOT
      mRNA is present in human tissues (heart > leukocytes >> fibroblasts), but no
      signal is detectable in the human hepatoma cell line HepG2. We mapped the human
      SCOT locus (OXCT) to the cytogenetic band 5p13 by in situ hybridization. From
      fibroblasts of a patient with hereditary SCOT deficiency, we amplified and cloned
      cDNA fragments containing the entire SCOT coding sequence. We found a homozygous
      C-to-G transversion at nt 848, which changes the Ser 283 codon to a stop codon.
      This mutation (S283X) is incompatible with normal enzyme function and represents
      the first documentation of a pathogenic mutation in SCOT deficiency.

PMID- 8751851
TI  - Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor,
      and familial persistent hyperinsulinemic hypoglycemia of infancy.
AB  - Familial persistent hyperinsulinemic hypoglycemia of infancy is a disorder of
      glucose homeostasis and is characterized by unregulated insulin secretion and
      profound hypoglycemia. Loss-of-function mutations in the second nucleotide
      binding fold of the sulfonylurea receptor, a subunit of the pancreatic-islet beta
      cell ATP-dependent potassium channel, has been demonstrated to be causative for
      persistent hyperinsulinemic hypoglycemia of infancy. We now describe three
      additional mutations in the first nucleotide-binding fold of the sulfonylurea
      receptor gene. One point mutation disrupts the highly conserved Walker A motif of
      the first nucleotide-binding-fold region. The other two mutations occur in
      noncoding sequences required for RNA processing and are predicted to disrupt the
      normal splicing pathway of the sulfonylurea-receptor mRNA precursor. These data
      suggest that both nucleotide-binding-fold regions of the sulfonylurea receptor
      are required for normal regulation of beta-cell ATP-dependent potassium channel
      activity and insulin secretion.

PMID- 8751853
TI  - Germ-line mutations in the neurofibromatosis 2 gene: correlations with disease
      severity and retinal abnormalities.
AB  - Neurofibromatosis 2 (NF2) features bilateral vestibular schwannomas, other benign
      neural tumors, and cataracts. Patients in some families develop many tumors at an
      early age and have rapid clinical progression, whereas in other families,
      patients may not have symptoms until much later and vestibular schwannomas may be
      the only tumors. The NF2 gene has been cloned from chromosome 22q; most
      identified germ-line mutations result in a truncated protein and severe NF2. To
      look for additional mutations and clinical correlations, we used SSCP analysis to
      screen DNA from 32 unrelated patients. We identified 20 different mutations in 21
      patients (66%): 10 nonsense mutations, 2 frameshifts, 7 splice-site mutations,
      and 1 large in-frame deletion. Clinical information on 47 patients from the 21
      families included ages at onset and at diagnosis, numbers of meningiomas, spinal
      and skin tumors, and presence of cataracts and retinal abnormalities. We compared
      clinical findings in patients with nonsense or frameshift mutations to those with
      splice-site mutations. When each patient was considered as an independent random
      event, the two groups differed (P < or = .05) for nearly every variable. Patients
      with nonsense or frameshift mutations were younger at onset and at diagnosis and
      had a higher frequency and mean number of tumors, supporting the correlation
      between nonsense and frameshift mutations and severe NF2. When each family was
      considered as an independent random event, statistically significant differences
      between the two groups were observed only for mean ages at onset and at
      diagnosis. A larger data set is needed to resolve these discrepancies. We
      observed retinal hamartomas and/or epiretinal membranes in nine patients from
      five families with four different nonsense mutations. This finding, which may
      represent a new genotype-phenotype correlation, merits further study.

PMID- 8751854
TI  - Decrease in the CGGn trinucleotide repeat mutation of the fragile X syndrome to
      normal size range during paternal transmission.
AB  - The fragile X syndrome, the most common inherited form of mental retardation, is
      caused by the expansion of a CGGn trinucleotide repeat in the FMR-1 gene.
      Although the repeat number usually increases during transmission, few cases with
      reduction of an expanded CGGn repeat back to the normal size range have been
      reported. We describe for the first time a family in which such reduction has
      occurred in the paternal transmission. The paternal premutation (delta = 300 bp)
      was not detected in one of the five daughters or in the son of this daughter,
      although he had the grandpaternal RFLP haplotype. Instead, fragments indicating
      the normal CGGn repeat size were seen on a Southern blot probed with StB12.3. PCR
      analysis of the CGGn repeat confirmed this; in addition to a maternal allele of
      30 repeats, an allele of 34 repeats was detected in the daughter and, further, in
      her son. Sequencing of this new allele revealed a pure CGGn repeat configuration
      without AGG interruptions. No evidence for a somatic mosaicism of a premutation
      allele in the daughter or a normal allele in her father was detected when
      investigating DNA derived from blood lymphocytes and skin fibroblasts. Another
      unusual finding in this family was lack of the PCR product of the microsatellite
      marker RS46 (DXS548) in one of the grandmaternal X chromosomes, detected as
      incompatible inheritance of RS46 alleles. The results suggest an
      intergenerational reduction in the CGGn repeat from premutation size to the
      normal size range and stable transmission of the contracted repeat to the next
      generation. However, paternal germ-line mosaicism could not be excluded as an
      alternative explanation for the reverse mutation.

PMID- 8751855
TI  - Genetic heterogeneity in hereditary breast cancer: role of BRCA1 and BRCA2.
AB  - The common hereditary forms of breast cancer have been largely attributed to the
      inheritance of mutations in the BRCA1 or BRCA2 genes. However, it is not yet
      clear what proportion of hereditary breast cancer is explained by BRCA1 and BRCA2
      or by some other unidentified susceptibility gene(s). We describe the proportion
      of hereditary breast cancer explained by BRCA1 or BRCA2 in a sample of North
      American hereditary breast cancers and assess the evidence for additional
      susceptibility genes that may confer hereditary breast or ovarian cancer risk.
      Twenty-three families were identified through two high-risk breast cancer
      research programs. Genetic analysis was undertaken to establish linkage between
      the breast or ovarian cancer cases and markers on chromosomes 17q (BRCA1) and 13q
      (BRCA2). Mutation analysis in the BRCA1 and BRCA2 genes was also undertaken in
      all families. The pattern of hereditary cancer in 14 (61%) of the 23 families
      studied was attributed to BRCA1 by a combination of linkage and mutation
      analyses. No families were attributed to BRCA2. Five families (22%) provided
      evidence against linkage to both BRCA1 and BRCA2. No BRCA1 or BRCA2 mutations
      were detected in these five families. The BRCA1 or BRCA2 status of four families
      (17%) could not be determined. BRCA1 and BRCA2 probably explain the majority of
      hereditary breast cancer that exists in the North American population. However,
      one or more additional genes may yet be found that explain some proportion of
      hereditary breast cancer.

PMID- 8751856
TI  - The relationship between trinucleotide (GAA) repeat length and clinical features
      in Friedreich ataxia.
AB  - Friedreich ataxia (FA) is associated with the expansion of a GAA trinucleotide
      repeat in the first intron of the X25 gene. We found both alleles expanded in 67
      FA patients from 48 Italian families. Five patients from three families were
      compound heterozygotes with expansion on one allele and an isoleucine-
      >phenylalanine change at position 154 on the other one. We found neither
      expansions nor point mutations in three patients. The length of FA alleles ranged
      from 201 to 1,186 repeat units, with no overlap with the normal range, and showed
      a negatively skewed distribution with a peak between 800 and 1,000 repeats. The
      FA repeat showed meiotic instability with a median variation of 150 repeats. The
      lengths of both larger and smaller alleles in each patient inversely correlated
      with age at onset of the disorder. Smaller alleles showed the best correlation,
      accounting for approximately 50% of the variation of age at onset. Mean allele
      length was significantly higher in patients with diabetes and in those with
      cardiomyopathy.

PMID- 8751857
TI  - CAG trinucleotide RNA repeats interact with RNA-binding proteins.
AB  - Genes associated with several neurological diseases are characterized by the
      presence of an abnormally long trinucleotide repeat sequence. By way of example,
      Huntington's disease (HD), is characterized by selective neuronal degeneration
      associated with the expansion of a polyglutamine-encoding CAG tract. Normally,
      this CAG tract is comprised of 11-34 repeats, but in HD it is expanded to > 37
      repeats in affected individuals. The mechanism by which CAG repeats cause
      neuronal degeneration is unknown, but it has been speculated that the expansion
      primarily causes abnormal protein functioning, which in turn causes HD pathology.
      Other mechanisms, however, have not been ruled out. Interactions between RNA and
      RNA-binding proteins have previously been shown to play a role in the expression
      of several eukaryotic genes. Herein, we report the association of cytoplasmic
      proteins with normal length and extended CAG repeats, using gel shift and UV
      crosslinking assays. Cytoplasmic protein extracts from several rat brain regions,
      including the striatum and cortex, sites of neuronal degeneration in HD, contain
      a 63-kD RNA-binding protein that specifically interacts with these CAG-repeat
      sequences. These protein-RNA interactions are dependent on the length of the CAG
      repeat, with longer repeats binding substantially more protein. Two CAG repeat
      binding proteins are present in human cortex and striatum; one comigrates with
      the rat protein at 63 kD, while the other migrates at 49 kD. These data suggest
      mechanisms by which RNA-binding proteins may be involved in the pathological
      course of trinucleotide repeat-associated neurological diseases.

PMID- 8751858
TI  - Polymorphism in the interferon-alpha gene family.
AB  - A pronounced genetic polymorphism of the interferon type I gene family has been
      assumed on the basis of RFLP analysis of the genomic region as well as the large
      number of sequences published compared to the number of loci. However, IFNA2 is
      the only locus that has been carefully analyzed concerning gene frequency, and
      only naturally occurring rare alleles have been found. We have extended the
      studies on a variation of expressed sequences by studying the IFNA1, IFNA2,
      IFNA10, IFNA13, IFNA14, and IFNA17 genes. Genomic white-blood-cell DNA from a
      population sample of blood donors and from a family material were screened by
      single-nucleotide primer extension (allele-specific primer extension) of PCR
      fragments. Because of sequence similarities, in some cases "nested" PCR was used,
      and, when applicable, restriction analysis or control sequencing was performed.
      All individuals carried the interferon-alpha 1 and interferon-alpha 13 variants
      but not the LeIF D variant. At the IFNA2 and IFNA14 loci only one sequence
      variant was found, while in the IFNA10 and IFNA17 groups two alleles were
      detected in each group. The IFNA10 and IFNA17 alleles segregated in families and
      showed a close fit to the Hardy-Weinberg equilibrium. There was a significant
      linkage disequilibrium between IFNA10 and IFNA17 alleles. The fact that the
      extent of genetic polymorphism was lower than expected suggests that a majority
      of the previously described gene sequences represent nonpolymorphic rare mutants
      that may have arisen in tumor cell lines.

PMID- 8751859
TI  - mtDNA polymorphism in East Asian Populations, with special reference to the
      peopling of Japan.
AB  - Nucleotide sequences of the major noncoding (D-loop) region of human mtDNA from
      five East Asian populations including mainland Japanese, Ainu, Ryukyuans,
      Koreans, and Chinese were analyzed. On the basis of a comparison of 482-bp
      sequences in 293 East Asians, 207 different sequence types were observed. Of
      these, 189 were unique to their respective populations, whereas 18 were shared
      between two or three populations. Among the shared types, eight were found in
      common between the mainland Japanese and Koreans, which is the largest number in
      the comparison. The intergenic COII/tRNA(Lys) 9-bp deletion was observed in every
      East Asian population with varying frequencies. The D-loop sequence variation
      suggests that the deletion event occurred only once in the ancestry of East
      Asians. Phylogenetic analysis revealed that East Asian lineages were classified
      into at least 18 monophyletic clusters, though lineages from the five populations
      were completely intermingled in the phylogenetic tree. However, we assigned 14 of
      the 18 clusters for their specificity on the basis of the population from which
      the maximum number of individuals in each cluster was derived. Of note is the
      finding that 50% of the mainland Japanese had continental specificity in which
      Chinese or Koreans were dominant, while < 20% of either Ryukyuans or Ainu
      possessed continental specificity. Phylogenetic analysis of the entire human
      population revealed the closest genetic affinity between the mainland Japanese
      and Koreans. Thus, the results of this study are compatible with the
      hybridization model on the origin of modern Japanese. It is suggested that
      approximately 65% of the gene pool in mainland Japanese was derived from the
      continental gene flow after the Yayoi Age.

PMID- 8751861
TI  - Localization of the familial Mediterranean fever gene (FMF) to a 250-kb interval
      in non-Ashkenazi Jewish founder haplotypes. The French FMF Consortium.
AB  - Chromosome 16p13.3 harbors a gene (MEF) associated with familial Mediterranean
      fever (FMF), a recessive disease very common in populations of Mediterranean
      ancestry. In the course of positional cloning of MEF, we genotyped 26 non
      Ashkenazi Jewish FMF pedigrees (310 meioses) with 15 microsatellite markers, most
      of which were recently developed by Genethon. Identification of recombination
      events in the haplotypes allowed narrowing of the MEF interval to a region
      between D16S3124 (telomeric) and D16S475 (centromeric). Two markers, D16S3070 and
      D16S3275, a microsatellite marker isolated from a YAC that also contains
      D16S3070, showed no recombination with the disease. Linkage disequilibrium and
      haplotype analysis highlighted the existence of a founder haplotype in our
      population. The core ancestral alleles were present in 71% of MEF-bearing
      chromosomes at loci D16S3070 and D16S3275. Furthermore, identification of
      historical crossing-over events in these pedigrees indicated that MEF is located
      between these two loci, which are both contained in a 250-kb genomic fragment.

PMID- 8751860
TI  - Evidence that specific mtDNA point mutations may not accumulate in skeletal
      muscle during normal human aging.
AB  - It is unclear at present whether specific mtDNA point mutations accumulate during
      normal human aging. In order to address this question, we used quantitative PCR
      of total DNA isolated from skeletal muscle from normal individuals of various
      ages to search for the presence and amount of spontaneous mtDNA point mutations
      in two small regions of the human mitochondrial genome. We observed low levels of
      somatic mutations above background in both regions, but there was no correlation
      between the amount of mutation detected and the age of the subject. These results
      contrasted with our finding of an age-related increase in the amount of the mtDNA
      "common deletion" in these very samples. Thus, it appears that both somatic mtDNA
      point mutations and mtDNA deletions can arise at low frequency in normal
      individuals but that, unlike deletions, there is no preferential amplification or
      accumulation of specific point mutations in skeletal muscle over the course of
      the normal human life span.

PMID- 8751862
TI  - A second locus for Rieger syndrome maps to chromosome 13q14.
AB  - Rieger syndrome is a genetically and phenotypically heterogeneous disorder
      typically characterized by malformations of the eyes, teeth, and umbilicus. The
      syndrome is inherited as an autosomal dominant trait and exhibits significant
      variable expressivity. One locus associated with this disorder has been mapped to
      4q25. Using a large four-generation pedigree, we have identified a second locus
      for Rieger syndrome located on chromosome 13q14.

PMID- 8751863
TI  - Homozygosity mapping of the gene for Chediak-Higashi syndrome to chromosome 1q42
      q44 in a segment of conserved synteny that includes the mouse beige locus (bg).
AB  - Chediak-Higashi syndrome (CHS) is an autosomal recessive disorder characterized
      by hypopigmentation or oculocutaneous albinism and severe immunologic deficiency
      with neutropenia and lack of natural killer (NK) cell function. Most patients die
      in childhood from pyogenic infections or an unusual lymphoma-like condition. A
      hallmark of the disorder is giant inclusion bodies seen in all granule-containing
      cells, including granulocytes, lymphocytes, melanocytes, mast cells, and neurons.
      Similar ultrastructural abnormalities occur in the beige mouse, which thus has
      been suggested to be homologous to human CHS. High-resolution genetic mapping has
      indicated that the bg gene region of mouse chromosome 13 is likely homologous to
      the distal portion of human chromosome 1q. Accordingly, we carried out
      homozygosity mapping using markers derived from distal human chromosome 1q in
      four inbred families or probands with CHS. Our results indicate that the human
      CHS gene maps to an 18.8-cM interval in chromosome segment 1q42-q44 and that
      human CHS therefore is very likely homologous to mouse bg.

PMID- 8751864
TI  - Genetic and physical mapping of the Chediak-Higashi syndrome on chromosome 1q42
      43.
AB  - The Chediak-Higashi syndrome (CHS) is a severe autosomal recessive condition,
      features of which are partial oculocutaneous albinism, increased susceptibility
      to infections, deficient natural killer cell activity, and the presence of large
      intracytoplasmic granulations in various cell types. Similar genetic disorders
      have been described in other species, including the beige mouse. On the basis of
      the hypothesis that the murine chromosome 13 region containing the beige locus
      was homologous to human chromosome 1, we have mapped the CHS locus to a 5-cM
      interval in chromosome segment 1q42.1-q42.2. The highest LOD score was obtained
      with the marker D1S235 (Zmax = 5.38; theta = 0). Haplo-type analysis enabled us
      to establish D1S2680 and D1S163, respectively, as the telomeric and the
      centromeric flanking markers. Multipoint linkage analysis confirms the
      localization of the CHS locus in this interval. Three YAC clones were found to
      cover the entire region in a conting established by YAC end-sequence
      characterization and sequence-tagged site mapping. The YAC contig contains all
      genetic markers that are nonrecombinant for the disease in the nine CHS families
      studied. This mapping confirms the previous hypothesis that the same gene defect
      causes CHS in human and beige pheno-type in mice and provides a genetic framework
      for the identification of candidate genes.

PMID- 8751865
TI  - Linkage disequilibrium analysis in young populations: pseudo-vitamin D-deficiency
      rickets and the founder effect in French Canadians.
AB  - Pseudo-vitamin D-deficiency rickets (PDDR) was mapped close to D12S90 and between
      proximal D12S312 and distal (D12S305, D12S104) microsatellites that were
      subsequently found on a single YAC clone. Analysis of a complex haplotype in
      linkage disequilibrium (LD) with the disease discriminated among distinct founder
      effects in French Canadian populations in Acadia and in Charlevoix-Saguenay-Lac
      Saint-Jean (Ch-SLSJ), as well as an earlier one in precolonial Europe. A simple
      demographic model suggested the historical age of the founder effect in Ch-SLSJ
      to be approximately 12 generations. The corresponding LD data are consistent with
      this figure when they are analyzed within the framework of Luria-Delbruck model,
      which takes into account the population growth. Population sampling due to a
      limited number of first settlers and the rapid demographic expansion appear to
      have played a major role in the founding of PDDR in Ch-SLSJ and, presumably,
      other genetic disorders endemic to French Canada. Similarly, the founder effect
      in Ashkenazim, coinciding with their early settlement in medieval Poland and
      subsequent expansion eastward, could explain the origin of frequent genetic
      diseases in this population.

PMID- 8751866
TI  - Linkage disequilibrium between an allele at the dopamine D4 receptor locus and
      Tourette syndrome, by the transmission-disequilibrium test.
AB  - Dopaminergic abnormalities are implicated in the pathogenesis of Tourette
      syndrome (TS) and chronic multiple tics. We used the transmission-disequilibrium
      test (TDT) method to test for linkage disequilibrium between a specific allele
      (the seven-repeat allele (DRD4*7R) of the exon 3 VNTR polymorphic site) at the D4
      dopamine receptor locus (DRD4) and expression of chronic multiple tics and TS.
      This particular allele had been shown in functional studies to have different
      binding properties compared with the other common alleles in this DRD4
      polymorphic system. We studied 64 family trios (consisting of an affected person
      and two parents, at least one heterozygous for DRD4*7R), including 12 nuclear
      family trios and 52 trios from four large TS kindreds. The DRD4*7R allele was
      transmitted significantly more frequently than expected (chi 2 TDT ranging from
      8.47 [P < .004] to 10.80 [P = .001], depending on breadth of disease definition
      and inclusion or exclusion of inferred genotypes). Confirmation of this finding
      will depend on either replication in other samples or the identification of a
      transmitted functional mutation within this sample.

PMID- 8751867
TI  - Linkage analysis of juvenile myoclonic epilepsy and microsatellite loci spanning
      61 cM of human chromosome 6p in 19 nuclear pedigrees provides no evidence for a
      susceptibility locus in this region.
AB  - Linkage analysis in separately ascertained families of probands with juvenile
      myoclonic epilepsy (JME) has previously provided evidence both for and against
      the existence of a locus (designated "EJM1"), on chromosome 6p, predisposing to a
      trait defined as either clinical JME, its associated electroencephalographic
      abnormality, or idiopathic generalized epilepsy. Linkage analysis was performed
      in 19 families in which a proband and at least one first- or two second-degree
      relatives have clinical JME. Family members were typed for seven highly
      polymorphic microsatellite markers on chromosome 6p: D6S260, D6S276, D6S291,
      D6S271, D6S465, D6S257, and D6S254. Pairwise and multipoint linkage analysis was
      carried out under the assumptions of autosomal dominant inheritance at 70% and
      50% penetrance and autosomal recessive inheritance at 70% and 50% penetrance. No
      significant evidence in favor of linkage to the clinical trait of JME was
      obtained for any locus. The region formally excluded (LOD score < -2) by using
      multipoint analysis varies depending on the assumptions made concerning
      inheritance parameters and the proportion of linked families, alpha-that is, the
      degree of locus heterogeneity. Further analysis either classifying all unaffected
      individuals as unknown or excluding a subset of four families in which
      pyknoleptic absence seizures were present in one or more individuals did not
      alter these conclusions.

PMID- 8751868
TI  - Evidence for major gene inheritance of Alzheimer disease in families of patients
      with and without apolipoprotein E epsilon 4.
AB  - Apolipoprotein E (APOE) genotype is the single most important determinant to the
      common form of Alzheimer disease (AD) yet identified. Several studies show that
      family history of AD is not entirely accounted for by APOE genotype. Also, there
      is evidence for an interaction between APOE genotype and gender. We carried out a
      complex segregation analysis in 636 nuclear families of consecutively ascertained
      and rigorously diagnosed probands in the Multi-Institutional Research in
      Alzheimer Genetic Epidemiology study in order to derive models of disease
      transmission which account for the influences of APOE genotype of the proband and
      gender. In the total group of families, models postulating sporadic occurrence,
      no major gene effect, random environmental transmission, and Mendelian
      inheritance were rejected. Transmission of AD in families of probands with at
      least one epsilon 4 allele best fit a dominant model. Moreover, single gene
      inheritance best explained clustering of the disorder in families of probands
      lacking epsilon 4, but a more complex genetic model or multiple genetic models
      may ultimately account for risk in this group of families. Our results also
      suggest that susceptibility to AD differs between men and women regardless of the
      proband's APOE status. Assuming a dominant model, AD appears to be completely
      penetrant in women, whereas only 62%-65% of men with predisposing genotypes
      develop AD. However, parameter estimates from the arbitrary major gene model
      suggests that AD is expressed dominantly in women and additively in men. These
      observations, taken together with epidemiologic data, are consistent with the
      hypothesis of an interaction between genes and other biological factors affecting
      disease susceptibility.

PMID- 8751870
TI  - Family study and segregation analysis of Tourette syndrome: evidence for a mixed
      model of inheritance.
AB  - To investigate the transmission of Tourette syndrome (TS) and associated
      disorders within families, complex segregation analysis was performed on family
      study data obtained from 53 independently ascertained children and adolescents
      with TS and their 154 first-degree relatives. The results suggest that the
      susceptibility for TS is conveyed by a major locus in combination with a
      multifactorial background. Other models of inheritance were definitively
      rejected, including strictly polygenic models, all single major locus models, and
      mixed models with dominant and recessive major loci. The frequency of the TS
      susceptibility allele was estimated to be .01. The major locus accounts for over
      half of the phenotypic variance for TS, whereas the multifactorial background
      accounts for approximately 40% of phenotypic variance. Penetrance estimates
      suggest that all individuals homozygous for the susceptibility allele at the
      major locus are affected, whereas only 2.2% of males and 0.3% of females
      heterozygous at the major locus are affected. Of individuals affected with TS,
      approximately 62% are heterozygous and approximately 38% are homozygous at the
      major locus. While none of the families had two parents affected with TS, 19% of
      families had two parents affected with the broader, phenotype, which includes TS,
      chronic tic disorder, or obsessive-compulsive disorder.

PMID- 8751869
TI  - Genetic variability in the tumor necrosis factor-lymphotoxin region influences
      susceptibility to rheumatoid arthritis.
AB  - The major histocompatibility complex class III tumor necrosis factor-lymphotoxin
      (TNF-LT) region (6p21.3) was investigated as a possible susceptibility locus for
      rheumatoid arthritis (RA). Inheritance of five TNF microsatellite markers was
      determined in 50 multiplex families. Overall, 47 different haplotypes were
      observed. One of these, the TNF a6, b5, c1, d3, e3 (H1) haplotype, was present in
      35.3% of affected, but in only 20.5% of unaffected, individuals (P < .005). This
      haplotype accounted for 21.5% of the parental haplotypes transmitted to affected
      offspring and only 7.3% not transmitted to affected offspring (P = .0003). The
      TNF a6 and TNF c1 alleles were individually associated with RA (P = .0005 and
      .0008, respectively), as were the HLA-DRB1 "shared epitope" (SE) (P = .0001) and
      HLA-DRB1*0401 (P = .0018). Both univariate and bivariate conditional logistic
      regression analysis showed significant effects of TNF c1 and SE in increasing
      risk to RA (P < .001). Stratification by the presence of SE indicated an
      independent effect of the TNFc1 allele (P = .0003) and the HLA A1, B8, DR3
      extended haplotype (always TNFa2, b3, c1, d1, e3) (P = .0027) in SE
      heterozygotes, while the H1 haplotype was associated with RA in SE homozygotes (P
      = .0018). The TNF-LT region appears to influence susceptibility to RA, distinct
      from HLA-DR.

PMID- 8751872
TI  - Genome scanning for linkage: an overview.
AB  - Several different methods for linkage analysis are shown to arise from a single
      likelihood function L for the observed allele-sharing data at multiple markers in
      a chromosomal region. These include classical parametric lod score methods,
      nonparametric or "model-free" affected pedigree-member (APM) methods, and the
      Gaussian process method. Setting the methods in the context of the likelihood
      function L clarifies their underlying assumptions. A test statistic derived from
      L, the efficient score statistic, is introduced. It is asymptotically equivalent
      to the lod score, but it can be easier to compute when the penetrances and
      frequencies of alleles of the trait gene are not known. APM test statistics and
      the Gaussian lod score are shown to be special cases of efficient score
      statistics. This unified framework facilitates exploration of a range of models
      for the effects of a putative trait-predisposing gene, and it facilitates
      sensitivity analyses to examine the consequences of model misspecification.

PMID- 8751871
TI  - Quantitative variation in obesity-related traits and insulin precursors linked to
      the OB gene region on human chromosome 7.
AB  - Despite the evidence that human obesity has strong genetic determinants, efforts
      at identifying specific genes that influence human obesity have largely been
      unsuccessful. Using the sibship data obtained from 32 low income Mexican American
      pedigrees ascertained on a type II diabetic proband and a multipoint variance
      components method, we tested for linkage between various obesity-related traits
      plus associated metabolic traits and 15 markers on human chromosome 7. We found
      evidence for linkage between markers in the OB gene region and various traits, as
      follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1
      (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin
      level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514
      explained 56% of the total phenotypic variation in extremity skinfolds. Variation
      at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and
      approximately 73% of phenotypic variation in split proinsulin concentration,
      respectively. Weaker evidence for linkage to several other obesity-related traits
      (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was
      observed for a genetic location, which is approximately 15 cM telomeric to OB. In
      conclusion, our study reveals that the OB region plays a significant role in
      determining the phenotypic variation of both insulin precursors and obesity
      related traits, at least in Mexican Americans.

PMID- 8751873
TI  - Selected locus and multiple panel models for radiation hybrid mapping.
AB  - We develop two new types of models for whole-genome radiation hybrid mapping
      using the general multipoint framework. The first, selected locus models, are
      appropriate for mapping markers in the region of a selectable locus that was used
      in creation of the hybrids. The models allow for strong retention of the
      selectable locus, with retention rates decreasing with increasing distance from
      the selectable locus in both directions. We illustrate the application of these
      models with 10 chromosome 17 sequence-tagged site (STS) markers and the thymidine
      kinase (TK) locus typed on a whole-genome hybrid panel in which TK was used in
      the selection process. The second set of models are appropriate when loci typed
      on two or more independent panels are to be used to build maps. Maps can be built
      assuming interlocus distances are independent or proportional between the panels,
      and the hypothesis of proportional distances can be tested. We illustrate the
      application of these models by using 27 chromosome 21 STS markers typed on two
      hybrid panels created with radiation doses of approximately 10,000 and
      approximately 50,000 Rads.

PMID- 8751874
TI  - A pseudolikelihood approach to correcting for ascertainment bias in family
      studies.
AB  - The Cannings and Thompson approach to correcting for ascertainment bias in family
      studies is extended to settings with multiple ascertainment. The extension is
      based on maximizing a pseudolikelihood. Two approaches to computing standard
      errors for the maximum pseudolikelihood estimate are described. One is especially
      simple to compute, while the other is more generally applicable. Simulation
      experiments suggest that the standard-error computations can be quite accurate.

PMID- 8751875
TI  - Evidence of linkage disequilibrium between schizophrenia and the SCa1 CAG repeat
      on chromosome 6p23.

PMID- 8751876
TI  - The genetic basis of Muir-Torre syndrome includes the hMLH1 locus.

PMID- 8751877
TI  - De novo duplication in Charcot-Marie-Tooth type 1A.

PMID- 8751878
TI  - Differentiation of the glucocerebrosidase gene from pseudogene by long-template
      PCR: implications for Gaucher disease.

PMID- 8751879
TI  - The genetics of traditional living: Y-chromosomal and mitochondrial lineages in
      the Sinai Peninsula.

PMID- 8751880
TI  - Nonsyndromic cleft lip with or without cleft palate: new BCL3 information.

PMID- 8751881
TI  - Nonsyndromic cleft lip with or without cleft palate: erratum.

PMID- 8751882
TI  - Immunoregulatory mechanisms of T-cell-dependent shock induced by a bacterial
      superantigen in mice.

PMID- 8751883
TI  - Opsonization of Cryptococcus neoformans by human anticryptococcal
      glucuronoxylomannan antibodies.
AB  - Cryptococcal meningitis occurs in 6 to 8% of human immunodeficiency virus
      infected individuals. Despite the availability of powerful antifungal agents that
      are active against Cryptococcus neoformans, these drugs generally fail to cure
      cryptococcal infections in immunocompromised hosts. Alternative approaches to
      prevention and therapy of cryptococcosis are urgently needed. Complement promotes
      phagocytosis of C. neoformans, but human antibodies to cryptococcal capsular
      polysaccharide have not been shown to function as complement-independent
      opsonins. The goal of our studies was to characterize the in vitro biological
      function of human antibodies to glucuronoxylomannan (GXM) from individuals
      immunized with a GXM-tetanus toxoid (GXM-TT) vaccine. We studied sera from nine
      vaccinees that manifested good serologic responses to GXM-TT. The results
      indicate that GXM-TT-elicited antibodies promote phagocytosis of C. neoformans by
      both murine J774 cells and human peripheral blood mononuclear cells (PBMCs). The
      two sera with the highest titers of anti-GXM immunoglobulin G2 antibodies were
      the most opsonic. When PBMC Fc gamma RIIa receptors were blocked, a 75% decrease
      in phagocytosis occurred following incubation of the PBMCs with C. neoformans
      opsonized with these sera. Our data indicate that, in the absence of complement,
      human anti-GXM-TT antibodies are opsonic and that antibodies of the
      immunoglobulin G2 isotype are effective opsonins.

PMID- 8751884
TI  - cis Elements and trans factors are both important in strain-specific regulation
      of the leukotoxin gene in Actinobacillus actinomycetemcomitans.
AB  - Actinobacillus actinomycetemcomitans, the etiologic agent of localized juvenile
      periodontitis, produces a potent leukotoxin that kills human neutrophils. The
      production of leukotoxin RNA can vary more than 50-fold among isolates of A.
      actinomycetemcomitans, and strains expressing high levels of leukotoxin RNA are
      most often found at sites of periodontal disease. To assess the relative
      contributions of transcription factors and promoter sequences in setting the
      disparate levels of leukotoxin RNA found, we have undertaken classical cis/trans
      analyses. First, the leukotoxin promoter regions from moderately leukotoxic (Y4)
      and minimally leukotoxic (ATCC 33384) strains of A. actinomycetemcomitans were
      cloned, sequenced, and compared with the previously sequences leukotoxin promoter
      region of the high-producer strain JP2. The Y4 and ATCC 33384 promoter regions
      each contain a 528-bp segment that is absent from JP2. Interestingly, the
      analysis of various deletion constructs in A. actinomycetemcomitans indicated
      that Y4, despite the large insertion, initiates leukotoxin RNA synthesis at the
      same promoter as JP2 does. To perform cis/trans analyses, these three leukotoxin
      promoter regions were cloned into a plasmid upstream of the reporter gene beta
      galactosidase. Each plasmid was transformed into JP2, Y4, and ATCC 33384, and the
      beta-galactosidase levels were determined. The results indicated that the
      sequences responsible for down-regulating leukotoxin RNA levels in Y4 relative to
      JP2 are found within the transcribed region of the Y4 leukotoxin operon.
      Importantly, in ATCC 33384, strain-specific trans factors and promoter sequence
      differences are equally significant in determining the lower levels of leukotoxin
      RNA. We hypothesize that either strain ATCC 33384 has a negative regulatory
      protein (which is missing or mutated in JP2/Y4) or that JP2 and Y4 carry an
      activator that is missing or mutated in ATCC 33384.

PMID- 8751886
TI  - Interactions between Campylobacter jejuni and lipids.
AB  - We previously showed that motility plays several key roles in Campylobacter
      jejuni pathogenesis, including increasing the efficiency of C. jejuni attachment
      to host epithelial cells. To further characterize C. jejuni attachment, we first
      examined the role of carbohydrates. Experiments with Chinese hamster ovary (CHO)
      cell mutants with defined defects in complex carbohydrate biosynthesis revealed
      that oligosaccharide sequences probably play a subordinate role in C. jejuni
      attachment to eukaryotic cells. Simple sugars such as mannose, fucose, glucose, N
      acetylglucosamine, maltose, and galactose also did not significantly alter the
      binding of C. jejuni to CHO cells. Thin-layer chromatography overlay analysis
      with lipids extracted from CHO cells suggested that C. jejuni binds to lipids.
      Lipid binding was further investigated using a receptor-based enzyme-linked
      immunosorbent assay. Hydrophobic interactions were determined to play a minor
      role in binding, since tetramethylurea, a strong inhibitor of hydrophobic
      interactions, did not significantly decrease binding between C. jejuni and
      lipids. The interaction was dissected further by comparing the binding of C.
      jejuni to lipids and their derivatives. The results showed that binding was
      greatest to the entire lipid structure and decreased in affinity when portions of
      the lipid were removed. Thin-layer chromatography overlay analysis showed that
      lipids with unsaturated fatty acids were bound with the highest affinity. Our
      results suggest that C. jejuni may interact with lipids in host cell membranes.
      However, lipids only partially inhibited C. jejuni binding to CHO cells,
      suggesting that multiple interactions occur between the bacteria and host cells.

PMID- 8751885
TI  - Anti-interleukin-4 modulation of the Th2 polarized response to the parasitic
      nematode Brugia pahangi.
AB  - Lymphatic filariasis is a chronic disease characterized by a pronounced Th2 bias
      in the immune response and impaired antigen (Ag)-specific Th1 responses. We have
      used a mouse model of filariasis to investigate the role of the infective form
      (the third-stage larvae [L3]) in modulating the immune response. Subcutaneous
      infection of BALB/c mice with L3 of Brugia pahangi has a profound effect on Th
      cell function. By day 12 post-infection, spleen cells from these mice exhibited a
      dramatic reduction in concanavalin A-driven proliferation and interleukin-2 (IL
      2) and gamma interferon (IFN-gamma) secretion in comparison with uninfected
      controls. However, exposure to L3 did not render the mice completely
      unresponsive; these animals mounted a strong Th2 response to the parasite,
      characterized by elevated levels of IL-4, IL-5, and IL-10 and parasite-specific
      serum immunoglobulin G (IgG), IgG1, and IgE. Treatment of spleen cells from L3
      infected mice with neutralizing anti-IL-4 or recombinant IL-2 resulted in a
      dramatic increase in concanavalin A-induced proliferation and IL-2 and IFN-gamma
      production. Despite their defective polyclonal Th1 response, cells from L3
      infected mice proliferated when stimulated with Ag, and this response was blocked
      by anti-IL-4. However, anti-IL-4 treatment failed to induce Ag-specific IL-2 or
      IFN-gamma production, indicating that B.pahangi-primed Th1 cells do not appear to
      be present or are still unable to respond even in the absence of IL-4.

PMID- 8751888
TI  - Hepatic tissue culture model for study of host-parasite interactions in alveolar
      echinococcosis.
AB  - An in vitro model for growth and differentiation of the metacestode tissue of the
      tapeworm Echinococcus multilocularis is described. This model simulates the
      organotropism of the parasite toward the liver of the intermediate host. In the
      presence of collagen-embedded primary hepatocytes from rats and humans, which can
      be kept in culture for 2 to 3 months, the parasitic vesicles grew by exogenous
      budding and multiplied about 12-fold within 3 weeks. In contrast, without the
      hepatocytes, the metacestodes rapidly degenerated. Development of protoscolices
      was seen only in the presence of rat hepatocytes but not in coculture of the
      metacestodes with hepatocytes of human origin, thus reflecting the in vivo
      situation during infection of rodents and in alveolar echinococcosis in humans.
      The experiments indicated that growth of the metacestodes and development of
      protoscolices depended on soluble low-molecular-weight factors released by the
      hepatocytes. The in vitro-grown metacestodes did not differ morphologically from
      the larvae found in infected intermediate hosts, and their infectivity was
      completely maintained. This report describes the first in vitro model of alveolar
      echinococcosis and will be the basis for future studies on host-parasite
      interactions of this important zoonosis.

PMID- 8751887
TI  - Differential regulation of cytokine and cytokine receptor mRNA expression upon
      infection of bone marrow-derived macrophages with Listeria monocytogenes.
AB  - Cytokine and cytokine receptor mRNA expression was analyzed by PCR-assisted
      amplification of RNA extracted from bone marrow-derived macrophages (BMM phi) at
      different time points after infection with Listeria monocytogenes. The mRNAs for
      the cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, and tumor necrosis
      factor alpha (TNF-alpha) were induced early after infection, whereas IL-6 mRNA
      appeared later and even nonhemolytic Listeria strains, which are unable to grow
      inside eukaryotic cells, induced the same cytokine mRNAs at levels similar to
      those of the wild-type strain. In most cases, the amounts of cytokines determined
      by various bioassays correlated with the level of mRNA induction. Inhibition of
      phagocytic uptake of L. monocytogenes by cytochalasin D treatment resulted in
      adherent bacteria which still induced the proinflammatory cytokines. In BMM phi,
      the level of IL-1 receptor II mRNA was unaffected, whereas mRNA expression of the
      two subtypes of tumor necrosis factor receptors (TNF-RI and TNF-RII) was
      differentially regulated upon infection: transcription of TNF-RI was reduced, and
      that of TNF-RII mRNA was induced. Similar to the decreased TNF-RI mRNA
      expression, gamma interferon receptor mRNA was downregulated in L. monocytogenes
      infected BMM phi. This dose- and time-dependent induction or downregulation of
      cytokine receptor mRNA following L. monocytogenes infection of BMM phi was not
      observed upon infection of established macrophage-like cell lines J774 and
      P388D1. Induction of IL-6 mRNA as well as IL-1 alpha/beta and TNF-alpha mRNAs
      upon L. monocytogenes infection of BMM phi occurs independently of autocrine TNF
      alpha signaling via TNF-RI or TNF-RII, as shown by infection of TNF-RI- and TNF
      RII-deficient macrophages derived from mutant B6 x 129 mice. In contrast to gamma
      interferon receptor mRNA, both TNF receptor subtype mRNAs were not influenced by
      L. monocytogenes infection of hybrid (B6 x 129) mouse macrophages. Whereas the
      proinflammatory cytokine mRNAs were even induced after infection with the
      nonpathogenic species L. innocua, no alteration of cytokine receptor mRNA
      expression was observed after challenge of BMM phi with this nonpathogenic
      species, suggesting that the modulation of cytokine and cytokine receptor
      expression by L. monocytogenes could be an important way of inhibition of
      macrophage stimulation.

PMID- 8751889
TI  - Partial characterization of a cell proliferation-inhibiting protein produced by
      Helicobacter pylori.
AB  - Despite the induction of an immunological reaction, Helicobacter pylori
      associated gastritis is a chronic disease, suggesting that this microbe can evade
      the host immune defense. Previous studies by our group showed that H. pylori
      suppresses the in vitro proliferative response of human mononuclear cells to
      mitogens and antigens. Here we demonstrate that the antiproliferative activity of
      H. pylori also affects the proliferation of various mammalian cell lines (U937,
      Jurkat, AGS, Kato-3, HEP-2, and P388D1). This effect is detectable in the first
      16 h of incubation and maximal between 24 and 48 h. In addition, the presence of
      H. pylori significantly diminished the protein synthesis of cells in the first 6
      h of incubation, comparable to the results with cycloheximide and diphtheria
      toxin. The urease enzyme, the cagA gene product, and the vacuolizing cytotoxin of
      H. pylori were excluded as causative agents of the antiproliferative effect by
      using isogenic knockout mutant strains. The inhibitory effect was not due to a
      lytic activity of this bacterium. The results reported here indicate that the
      responsible factor is a protein with an apparent native molecular mass of 100 +/-
      10 kDa. Our work implicates the presence of a protein factor in H. pylori (termed
      PIP [for proliferation-inhibiting protein]) with antiproliferative activity for
      mammalian cells, including immunocompetent and epithelial cells. Thus, it is
      reasonable to presume that this property may contribute to the pathogenesis of H.
      pylori-induced diseases. It may be involved on the one hand in immune response
      evasion and on the other hand in the suppression of epithelial repair mechanisms.

PMID- 8751890
TI  - The Escherichia coli K-12 gntP gene allows E. coli F-18 to occupy a distinct
      nutritional niche in the streptomycin-treated mouse large intestine.
AB  - Escherichia coli F-18 is a human fecal isolate that makes type 1 fimbriae,
      encoded by the fim gene cluster, and is an excellent colonizer of the
      streptomycin-treated mouse intestine. E. coli F-18 fimA::tet, lacking type 1
      fimbriae, was constructed by bacteriophage P1 transduction of the fim region of
      the E. coli K-12 strain ORN151, containing the tetracycline resistance gene from
      Tn10 inserted in the fimA gene, into E. coli F-18. E. coli F-18 fimA::tet was
      found to occupy a distinct niche in the streptomycin-treated mouse intestine when
      fed in small numbers (10(4) CFU) to mice, along with large numbers (10(10) CFU)
      of E. coli F-18, as defined by the ability of the E. coli F-18 fimA::tet strain
      to grow and colonize only 1 order of magnitude below E. coli F-18. The same
      effect was observed when mice already colonized with E. coli F-18 were fed small
      numbers of E. coli F-18 fimA::tet. Experiments which show that the E. coli K-12
      gene responsible for this effect is not fim::tet but gntP, which maps immediately
      downstream of the fim gene cluster, are presented. gntP encodes a high-affinity
      gluconate permease, suggesting that the distinct niche in the mouse large
      intestine is defined by the presence of gluconate. The data presented here
      support the idea that small numbers of an ingested microorganism can colonize the
      intestine as long as it can utilize an available nutrient better than any of the
      other resident species can.

PMID- 8751891
TI  - Escherichia coli F-18 and E. coli K-12 eda mutants do not colonize the
      streptomycin-treated mouse large intestine.
AB  - The Escherichia coli human fecal isolates F-18 and K-12 are excellent colonizers
      of the streptomycin-treated mouse intestine. E. coli F-18 and E. coli K-12 eda
      mutants (unable to utilize glucuronate, galacturonate, and gluconate) were
      constructed by insertional mutagenesis. Neither the E. coli F-18 eda nor the E.
      coli K-12 eda mutant was able to colonize the streptomycin-treated mouse
      intestine, whether they were fed to mice together with their respective parental
      strains or alone. Complementation of the eda mutants with pTC190 (containing a
      functional E. coli K-12 eda gene) completely restored the colonization ability of
      both eda mutants. Relative to their parental strains, the E. coli F-18 eda mutant
      and the E. coli K-12 eda mutant grew poorly in cecal mucus isolated from mice fed
      either normal mouse chow or a synthetic diet containing sucrose as the sole
      carbon source, yet the mutants and parental strains demonstrated identical growth
      rates in minimal medium with glucose as the carbon source. E. coli F-18 edd eda
      and E. coli K-12 edd eda double mutants colonized the streptomycin-treated
      intestine when fed to mice alone; however, when fed simultaneously with their
      respective parental strains, they were poor colonizers. Since the edd gene is
      involved only in gluconate metabolism via the Entner-Doudoroff pathway, these
      results implicate the utilization of gluconate and the Entner-Doudoroff pathway
      as important elements in E. coli colonization of the streptomycin-treated mouse
      large intestine.

PMID- 8751892
TI  - Involvement of superoxide and myeloperoxidase in oxygen-dependent killing of
      Staphylococcus aureus by neutrophils.
AB  - We have used a quantitative assay that measures independent rate constants for
      phagocytosis and killing of Staphylococcus aureus to investigate the involvement
      of superoxide and myeloperoxidase in bacterial killing by human neutrophils. To
      inhibit superoxide-dependent processes, superoxide dismutase was cross-linked to
      immunoglobulin G and the conjugate was attached to the surface of S. aureus via
      protein A in its cell wall. Myeloperoxidase was inhibited with azide, and
      myeloperoxidase-deficient neutrophils were used. Adding the NADPH oxidase
      inhibitor diphenyleneiodonium, to prevent superoxide production, decreased the
      killing rate to 25%, indicating that oxidative killing mechanisms predominate in
      this system. The rate constant for killing of S. aureus with superoxide dismutase
      attached was 70% of that for control bacteria linked to inactivated enzyme.
      Superoxide dismutase had no effect in the presence of diphenyleneiodonium. The
      rate of killing was decreased to 33% in the presence of azide and to 40% with
      myeloperoxidase-deficient neutrophils. Superoxide dismutase had no effect in the
      presence of azide. On the assumption that the oxidative and nonoxidative
      components of killing can be considered separately, the oxidative rate was
      decreased by almost half by superoxide dismutase and was about six times lower
      when myeloperoxidase was inactive. We conclude that myeloperoxidase-dependent
      processes are strongly favored by human neutrophils as their prime mechanism of
      oxidative killing of S. aureus and that superoxide makes a direct contribution to
      killing. Our results also suggest that superoxide acts in conjunction with a
      myeloperoxidase-dependent pathway.

PMID- 8751893
TI  - Experimental vaccination against group B streptococcus, an encapsulated
      bacterium, with highly purified preparations of cell surface proteins Rib and
      alpha.
AB  - Encapsulated bacteria cause some of the most common diseases in humans. Although
      the polysaccharide capsules of these pathogens have attracted the most attention
      with regard to vaccine development, recent evidence suggests that bacterial
      surface proteins may also be used to confer protective immunity. We have analyzed
      this possibility in group B streptococcus (GBS), an encapsulated bacterium that
      is the major cause of invasive bacterial disease in the neonatal period. Previous
      work has shown that the majority of GBS strains causing invasive infections
      express the Rib protein, and that most strains lacking Rib express a protein
      designated alpha. Here we report that active immunization with highly purified
      preparations of Rib or alpha protected mice against lethal infection with strains
      expressing the corresponding protein. Vaccination with the Rib protein protected
      against two strains of capsular type III and two strains of type II, and
      vaccination with the alpha protein protected against one strain of type II and
      one strain of type Ib. The mice vaccinated with Rib or alpha showed a good
      immunoglobulin G response to the immunogen. These data suggest that a vaccine
      against GBS disease may be based on cell surface proteins and support the notion
      that proteins may be used for immunization against encapsulated bacteria.

PMID- 8751894
TI  - Requirement for exported proteins in secretion through the invasion-associated
      type III system of Salmonella typhimurium.
AB  - The inv and spa loci of Salmonella typhimurium encode a type III protein
      secretion system which is essential for the ability of this microorganism to gain
      access to cultured epithelial cells. These loci are located at centisome 63 in
      the Salmonella chromosome. We have carried out a functional analysis of several
      genes of these loci and have found that two exported proteins encoded in this
      region, InvJ and SpaO, are required for secretion through the invasion-associated
      type III secretion system. These findings suggest the existence of a hierarchy in
      the export process, since mutations in other targets of this secretory system
      have no effect on protein secretion. We have also shown that the spaO, spaP,
      spaQ, and spaR genes are required for protein secretion and for the ability of S.
      typhimurium to gain access to cultured epithelial cells. In addition, we
      investigated the ability of an invJ S. typhimurium mutant strain to present the
      SipB protein to the bacterial surface and demonstrated that, in contrast to
      Spa32, its putative Shigella homolog, InvJ is not involved in the surface
      presentation of the Sip proteins.

PMID- 8751895
TI  - Cytokines and antibody subclass associated with protective immunity against blood
      stage malaria in mice vaccinated with the C terminus of merozoite surface protein
      1 plus a novel adjuvant.
AB  - A blood-stage malaria antigen comprising the C terminus of merozoite surface
      protein 1 fused to glutathione S-transferase, combined with an adjuvant
      formulation containing squalane, Tween 80, and pluronic L121 (AF), administered
      subcutaneously protected mice against death from a lethal Plasmodium yoelii
      infection. The protection induced by this antigen-adjuvant combination was
      compared with that induced by the antigen plus saponin in terms of survival from
      the lethal infection and clearance of parasitemia. The levels of gamma interferon
      and interleukin-4 in spleens were measured as indicators of Th1 and Th2 cell
      activation, and antibody classes and subclasses were determined by
      immunofluorescence. With a 10-micrograms dose of antigen and AF as adjuvant, all
      mice recovered, but with saponin as the adjuvant, there were only a few
      survivors. With 30 micrograms of antigen plus AF, the peak parasitemias were 10
      fold lower than those with 10 micrograms; with saponin, survival was slightly
      improved. The levels of both gamma interferon and interleukin-4 rose more rapidly
      and to higher levels with AF as the adjuvant than with saponin, and the same was
      true for immunoglobulin G1 (IgG1), IgG2a, and IgG2b subclasses. Thus, in terms of
      both cytokine production and antibody levels, AF is a more potent adjuvant for a
      malaria vaccine than is saponin.

PMID- 8751896
TI  - Molecular characterization of a Campylobacter jejuni 29-kilodalton periplasmic
      binding protein.
AB  - Campylobacter jejuni, a gram-negative, microaerophilic, spiral bacterium, is a
      common cause of human gastrointestinal disease. Although investigators commonly
      use C. jejuni glycine-hydrochloride extracts in assays to determine the products
      that promote the binding of the organism to eukaryotic cells, the proteins
      contained within these extracts remain ill defined. Characterization of these
      proteins will provide a better understanding of C. jejuni gene regulation and
      organization. An antiserum was raised against a C. jejuni 29-kDa gel-purified
      protein detected in glycine-hydrochloride extracts. This antiserum was used to
      screen an expression library of C. jejuni. A reactive clone that contained an
      open reading frame of 256 amino acids was identified. The cloned gene was
      transcribed and translated, and the product was exported to the periplasmic space
      in Escherichia coli XL1-Blue. The translated C. jejuni product, designated P29,
      exhibited significant similarity to the histidine and lysine-arginine-ornithine
      periplasmic binding proteins (HisJ and LAO, respectively) of Salmonella
      typhimurium. The C. jejuni gene encoding the P29 protein complemented an S.
      typhimurium HisJ mutant but not a LAO mutant when provided in trans. These data
      suggest that the C. jejuni gene encoding the P29 protein is a homolog of the S.
      typhimurium hisJ gene.

PMID- 8751897
TI  - Monoclonal antibodies that recognize a common pneumococcal protein with
      similarities to streptococcal group A surface glyceraldehyde-3-phosphate
      dehydrogenase.
AB  - Monoclonal antibodies (MAbs) against clinical isolates of Streptococcus
      pneumoniae were produced in a search for common pneumococcal proteins. One of the
      fusions generated two MAbs, 174,B-8 (immunoglobulin G2a) and 177,D-8
      (immunoglobulin G1), which by Western blotting (immunoblotting) stained with a
      main band of 40 kDa found in all isolates of S. pneumoniae examined. Cross
      reactivity studies with streptococci other than pneumococci revealed very weak or
      moderate reactions with the MAbs. The 40-kDa protein was isolated by
      immunoaffinity chromatography and subsequent preparative Western blotting. N
      terminal amino acid sequencing showed 90% amino acid sequence homology with a
      surface-located glyceraldehyde-3-phosphate dehydrogenase from Streptococcus
      pyogenes. This protein has also been reported to exhibit binding to mammalian
      proteins such as fibronectin, which may serve as host receptors. The epitopes for
      MAbs 174,B-8 and 177,D-8 reacting with the pneumococcal analog were not
      accessible to antibody binding in live bacteria but were exposed after heat
      killing. The MAbs showed negligible cross-reactions with S. pyogenes.

PMID- 8751898
TI  - Fungal beta-glucan interacts with vitronectin and stimulates tumor necrosis
      factor alpha release from macrophages.
AB  - beta-Glucans are polymers of D-glucose which represent major structural
      components of fungal cell walls. It was shown previously that fungi interact with
      macrophages through beta-glucan receptors, thereby inducing release of tumor
      necrosis factor alpha (TNF-alpha). Additional studies demonstrated that
      vitronectin, a host adhesive glycoprotein, binds to fungi and enhances macrophage
      recognition of these organisms. Since vitronectin contains a carbohydrate-binding
      region, we postulated that vitronectin binds fungal beta-glucans and subsequently
      augments macrophage TNF-alpha release in response to this fungal component. To
      study this, we first determined the release of TNF-alpha from alveolar
      macrophages stimulated with fungal beta-glucan. Maximal TNF-alpha release
      occurred with moderate concentrations of beta-glucan (100 to 200 micrograms/ml),
      whereas higher concentrations of beta-glucan (> or = 500 micrograms/ml) caused
      apparent suppression of the TNF-alpha activity released. This suppression of TNF
      alpha activity by high concentrations of beta-glucan was mediated by the
      particulate beta-glucan binding soluble TNF-alpha, through the lectin-binding
      domain of the cytokine, rendering the TNF-alpha less available for measurement.
      Next, we assessed the interaction of vitronectin with beta-glucan. Binding of
      125I-vitronectin to particulate fungal beta-glucan was dose dependent and
      specifically inhibitable by unlabeled vitronectin. Furthermore, treatment of beta
      glucan with vitronectin substantially augmented macrophage TNF-alpha release in
      response to this fungal component. These findings demonstrate that fungal beta
      glucan can directly modulate TNF-alpha release from macrophages. Further, these
      studies indicate that the host adhesive glycoprotein vitronectin specifically
      binds beta-glucan and augments macrophage cytokine release in response to this
      fungal element.

PMID- 8751899
TI  - Identification of surface-exposed linear B-cell epitopes of the nonfimbrial
      adhesin CS31A of Escherichia coli by using overlapping peptides and antipeptide
      antibodies.
AB  - As a first step toward the design of an epitope vaccine, by using the nonfimbrial
      adhesin CS31A of Escherichia coli as a carrier, a low-resolution topological and
      epitope map of the CS31A subunit was developed by using solid-phase peptide
      synthesis and polyclonal rabbit antibodies raised against both native and
      denatured proteins. Peptides constituting antigenic epitopes on the major subunit
      (ClpG) of the multimeric CS31A antigen were identified by examining the binding
      of the antibodies to 249 overlapping nonapeptides covering the amino acid
      sequence of ClpG. With antibodies raised against denatured ClpG subunit, seven
      major epitope regions, corresponding to residues 10 to 18, 45 to 58, 88 to 107,
      148 to 172, 187 to 196, 212 to 219, and 235 to 241, were located. Most of the
      epitopes were hydrophilic and were located in variable regions, residing largely
      in loop regions at the boundaries of secondary structural elements of ClpG. In
      contrast, antibodies raised against native CS31A antigen reacted only with the
      peptide AVNPNA (positions 179 to 184), demonstrating that this peptide was the
      only linear B-cell epitope of the native protein. The different immunogenic
      profiles of native CS31A antigen and denatured ClpG indicated that the
      denaturation process resulted in marked conformational changes in the protein,
      which could expose epitopes hidden or absent in native CS31A. To identify the
      surface-exposed epitopes, nine peptides covering the dominant antigenic regions
      of ClpG were synthesized and used to prepare site-specific antibodies.
      Antipeptide antibodies were tested, in a competitive enzyme-linked immunosorbent
      assay (ELISA), for cross-reactivity with native CS31A and denatured ClpG subunit.
      Four of these antipeptide antibodies bound to the native protein in an
      accessibility ELISA, indicating that residues 44 to 56, 174 to 190, 185 to 199,
      and 235 to 249 were surface exposed on CS31A. These data indicate that an
      immunodominant surface-exposed linear epitope was present in the region from
      positions 179 to 184 of ClpG in the native CS31A antigen on intact bacterial
      cells and suggest that the four surface-exposed epitopes constitute potential
      sites for insertions or substitutions with heterologous peptides.

PMID- 8751900
TI  - Construction and characterization of a potential live oral carrier-based vaccine
      against Vibrio cholerae O139.
AB  - The rfb region from Vibrio cholerae O139 strain MO45 was cloned from cosmid gene
      banks established in Escherichia coli HB101, using an immunoblot assay for
      screening of the correct clones. Immunoblot analysis of lipopolysaccharide (LPS)
      preparations revealed the presence of two types of positive clones: (i) those
      expressing only a short core-linked O polysaccharide (SOPS) and (ii) those also
      expressing a highly polymerized capsular polysaccharide (CPS) not bound to the E.
      coli K-12 LPS core. In addition, the latter clones appear to contain a locus
      which may encode a putative regulator of SOPS and CPS chain length. Further
      characterization in E. coli showed that CPS constitutes a barrier against large
      particles such as the bacteriophage Ffm but not against bacteriophage lambda or
      P1. In addition, a portion of the K-12 LPS core may not be substituted with SOPS.
      Loci associated with the two clonal types were transferred into V. cholerae CH19,
      an rfbAB deletion mutant of CVD103-HgR deficient in the production of the
      homologous Inaba O polysaccharide. This resulted in the stable expression of
      SOPS, alone or together with CPS, that was indistinguishable from that of wild
      type V. cholerae O139. Strains CH25 and CH26, which correspond to CH19 bearing
      the V. cholerae O139 rfb region integrated into the chromosome, were found to be
      genetically stable and essentially identical to the parent CVD103-HgR with
      respect to physiological properties such as cell motility, mercury resistance,
      toxicity, and production of the cholera toxin B subunit. Rabbits immunized with
      CH25 elicited high titers of anti-O139 SOPS- and CPS-specific serum antibodies.
      These strains possess characteristics desirable in candidate live oral vaccines
      against V. cholerae O139.

PMID- 8751901
TI  - Inducible immunity to Trichomonas vaginalis in a mouse model of vaginal
      infection.
AB  - We studied the protective effect of subcutaneous immunization with Trichomonas
      vaginalis in a mouse model of vaginal infection. BALB/c mice were immunized with
      various doses of T. vaginalis (4.5 x 10(5), 9 x 10(6), and 1 x 10(8) organisms
      per ml) suspended in Freund's complete adjuvant 56 days prior to vaginal
      infection and were given booster injections of the same doses of T. vaginalis in
      Freund's incomplete adjuvant 4 weeks later. Control mice were immunized and given
      booster injections of phosphate-buffered saline suspended in Freund's complete
      and incomplete adjuvants. The mice were tail bled and vaginal washes were
      performed at weekly intervals for 4 weeks to determine the isolation of T.
      vaginalis and the serum and vaginal antibody reactivity. Mice which had been
      immunized and given booster immunizations had significantly fewer intravaginal
      infections and had increased serum and vaginal antibody responses compared with
      those of control mice (P < 0.01). Mice that were vaginally infected, treated with
      metronidazole, and then reinfected vaginally did not develop protective immunity.
      Subcutaneous immunization with whole T. vaginalis organisms appears to confer
      protection against intravaginal challenge with T. vaginalis, protection which is
      not achieved as a result of prior vaginal infection.

PMID- 8751902
TI  - Variation in repeat number within the alpha C protein of group B streptococci
      alters antigenicity and protective epitopes.
AB  - Variable expression of repeating units of the protective alpha C proteins among
      clinical isolates of group B streptococci (GBS) may have implications for vaccine
      development. In this study, alpha C protein genes containing various numbers of
      repeats (1,2,9, and 16) were cloned in a T7 overexpression vector in Escherichia
      coli. Expression was induced by isopropyl-beta-D-thiogalactopyranoside, and
      proteins were purified by anion-exchange, gel filtration, or affinity
      chromatography or by isoelectric focusing. Rabbits were immunized with purified 1
      ,2-,9-, or 16-repeat proteins. All proteins appeared to be highly immunogenic.
      Enzyme-linked immunosorbent assay inhibition with 9-repeat protein as the coating
      antigen and 9-repeat-antigen-elicited antiserum showed that a 200-fold-higher
      concentration of 1-repeat antigen than of 9- or 16-repeat antigen was required
      for 50% inhibition of antibody-antigen binding. The concentration of 2-repeat
      antigen required for 50% inhibition was intermediate relative to the
      concentrations of 1- and 9-repeat antigens. These results suggested that
      antibodies to 9-repeat antigen recognized predominantly a conformational
      epitope(s) contained in proteins with higher numbers of repeats (9 or 16) but
      lost considerable binding affinities for an epitope(s) contained in alpha C
      proteins with fewer repeats (1 or 2). Similar results were obtained with
      antiserum to 16-repeat antigen. However, antibodies to 1- and 2-repeat antigens
      recognized 1-,2-,9-,and 16-repeat antigens with equal binding affinities. This
      finding suggested that 1- and 2-repeat-elicited antibodies recognized an
      epitope(s) on individual repeats. Loss of repeating units from the alpha C
      proteins may result in decreased protection because the loss of epitopes
      (including conformational epitopes) gives the microorganisms the opportunity to
      escape host antibodies. If 1- and 2-repeat-elicited antibodies bind all alpha C
      proteins with equal affinity, regardless of their repeat number, they may prevent
      GBS strains with fewer repeats from escaping host immunity. Protection data
      obtained with antisera to the proteins with different repeat numbers support this
      hypothesis: mouse pups challenged with GBS strain A909 were better protected when
      immunized with 1- or 2-repeat-elicited antiserum (76 and 75%, respectively) than
      when immunized with 9- or 16-repeat-elicited antiserum (41 and 48%,
      respectively).

PMID- 8751903
TI  - Seroprevalence and specificity of human responses to the Plasmodium falciparum
      rhoptry protein Rhop-3 determined by using a C-terminal recombinant protein.
AB  - Rhoptry proteins participate in invasion of erythrocytes by malaria parasites.
      Antibodies to some of these proteins can inhibit invasion and partially protect
      monkeys from disease. To examine human serological responses to the 110-kDa
      component (Rhop-3) of the high-molecular-weight rhoptry protein complex, two cDNA
      clones corresponding to Rhop-3 were identified by immunologic screening. A
      recombinant protein representing the C-terminal one-third of the Rhop-3 was used
      to assess the seroprevalence to this protein in geographically isolated
      populations with different patterns of malaria transmission. The immunoglobulin G
      (IgG) positivity rate for the recombinant Rhop-3 in an enzyme-linked
      immunosorbent assay was 30% in an area of Papua New Guinea where malaria is
      holoendemic. In Kenya, the prevalence rates were 43 and 36%, respectively, in an
      area of hyperendemicity and an area of seasonal transmission. By contrast, rates
      of IgG seroprevalence to an extract of Gambian strain of Plasmodium falciparum
      were 48, 90, and 97% respectively, in these populations. In these areas, the
      pattern of antibody recognition of Rhop-3 is more similar (1.7-fold maximum
      difference) than the parasite extract (5-fold difference). The difference in
      seroresponses may represent antigenic polymorphism in different parasite strains,
      while their similarity for the Rhop-3 fragment may represent conservation of this
      protein. Recombinant- and parasite extract-specific IgG was not found in
      individuals infected only with Plasmodium vivax. Cross-reactivity was seen in the
      IgM assay. In Mombasa (Kenya), maternal and cord Rhop-3-specific IgG activities
      were similar. Fetal antigen-specific IgM reactivity was generally undetectable
      for all antigens.

PMID- 8751904
TI  - Potent CD14-mediated signalling of human leukocytes by Escherichia coli can be
      mediated by interaction of whole bacteria and host cells without extensive prior
      release of endotoxin.
AB  - How invading microorganisms are detected by the host has not been well defined.
      We have compared the abilities of Escherichia coli and lipopolysaccharides (LPS)
      purified from these bacteria to prime isolated neutrophils for phorbol myristate
      acetate-stimulated arachidonate release, to trigger respiratory burst in 1%
      blood, and to increase steady-state levels of tumor necrosis factor alpha mRNA in
      whole blood. In all three assays, bacteria were > or = 10-fold more potent than
      equivalent amounts of LPS and could trigger maximal cellular responses at ratios
      as low as one bacterium per 20 to 200 leukocytes. Both E. coli and LPS-triggered
      responses were enhanced by LPS-binding protein and inhibited by an anti-CD14
      monoclonal antibody and the bactericidal/permeability-increasing protein (BPI).
      However, whereas O polysaccharide did not affect the potency of isolated LPS,
      intact E. coli carrying long-chain LPS (O111:B4) was less potent than rough E.
      coli (J5). Furthermore, material collected by filtration or centrifugation of
      bacteria incubated under conditions used to trigger arachidonate release or
      chemiluminescence was 5- or 30-fold less active, respectively, than whole
      bacterial suspensions. Extracellular BPI (not bound to bacteria) inhibited
      bacterial signalling, but BPI bound to bacteria was much more potent. Taken
      together, these findings indicate that E. coli cells can strongly signal their
      presence to human leukocytes not only by shedding LPS into surrounding fluids but
      also by exposing endotoxin at or near their surface during direct interaction
      with host cells.

PMID- 8751905
TI  - Helicobacter pylori and Porphyromonas gingivalis lipopolysaccharides are poorly
      transferred to recombinant soluble CD14.
AB  - Helicobacter pylori and Porphyromonas gingivalis are gram-negative bacteria
      associated with chronic inflammatory diseases. These bacteria possess
      lipopolysaccharides (LPSs) that are able to activate human monocytes to produce
      tumor necrosis factor alpha but fail to activate human endothelial cells to
      express E-selectin. With Escherichia coli LPS, tumor necrosis factor alpha
      activation requires membrane-bound CD14 and E-selectin expression requires
      soluble CD14 (sCD14). Therefore, the ability of H. pylori and P. gingivalis LPSs
      to transfer to and bind sCD14 was examined by using immobilized recombinant sCD14
      and human serum or recombinant LPS-binding protein (LBP). H. pylori and P.
      gingivalis LPSs were transferred to sCD14 when serum or LBP was present. However,
      the transfer of these LPSs to CD14 in serum was significantly slower than the
      transfer of E. coli LPS. Quantitation of the transfer rates by Michaelis-Menten
      kinetics yielded K(m) values of 6 and 0.1 nM for H. pylori and E. coli LPSs,
      respectively. The amount of P. gingivalis LPS required to obtain half-maximum
      binding to CD14 was approximately 10-fold greater than the amount of E. coli LPS
      required. The slower transfer rates displayed by these LPSs can be explained by
      the poor binding to LBP observed in direct binding assays. These results are
      consistent with the proportionately lower ability of these LPSs to activate
      monocytes compared with E. coli LPS. However, the ability of H. pylori and P.
      gingivalis LPSs to bind LBP and transfer to sCD14 demonstrates that the lack of
      endothelial cell CD14-dependent cell activation by these LPSs occurs distal to
      sCD14 binding.

PMID- 8751906
TI  - Interleukin-12 regulation of host defenses against Coccidioides immitis.
AB  - We have previously reported on the alternate regulation of gamma interferon (IFN
      gamma) and interleukin-4 (IL-4) in inbred mouse strains which differ in their
      susceptibility to Coccidioides immitis. The genetically resistant DBA/2 mice
      manifest a predominant T-helper 1 (Th1) response, with early production of IFN
      gamma, whereas susceptible BALB/c mice show an early production of the Th2
      cytokine IL-4. Since IL-12 is one cytokine that can act early during host
      defenses to promote the differentiation of cytokine production towards IFN-gamma
      and thus may promote expression of a protective immune response, we investigated
      the role of IL-12 in resistance to C. immitis. Administration of recombinant IL
      12 to the susceptible mouse strain before and after systemic (intraperitoneal)
      challenge with C. immitis significantly ameliorated the course of the disease, as
      measured by a reduction in the fungal load in the lungs, liver, and spleen.
      Analysis of the cytokine mRNA in lungs from infected BALB/c mice revealed that
      the protective effect of recombinant IL-12 was accompanied by a shift from a Th2
      to a Th1 response. The importance of IL-12 in resistance to this fungus was
      further established by showing that neutralization of endogenous IL-12 in the
      resistant DBA/2 mouse strain led to a significant increase in the fungal burden
      in pulmonary and extrapulmonary tissues. These results establish that IL-12 plays
      a pivotal role in the host defense against systemic challenge with C. immitis.

PMID- 8751907
TI  - Immunization of Aotus nancymai with recombinant C terminus of Plasmodium
      falciparum merozoite surface protein 1 in liposomes and alum adjuvant does not
      induce protection against a challenge infection.
AB  - Merozoite surface protein 1 (MSP-1) of Plasmodium falciparum is an antimalarial
      vaccine candidate. The highly conserved 19-kDa C-terminal processing fragment of
      MSP-1 (MSP-1(19)) is of particular interest since it contains epitopes recognized
      by monoclonal antibodies which inhibit the invasion of erythrocytes in vitro. The
      presence of naturally acquired anti-MSP-1(19) antibodies in individuals exposed
      to malaria has been correlated with reduced morbidity, and immunization with an
      equivalent recombinant P. yoelii antigen induces substantial protection against
      this parasite in mice. We have expressed P. falciparum MSP-1(19) in Escherichia
      coli as a correctly folded protein and immunized Aotus nancymai monkeys by using
      the protein incorporated into liposomes and adsorbed to alum. After vaccination,
      the sera from these animals contained anti-MSP-1(19) antibodies, some of which
      competed for binding to MSP-1(19) with monoclonal antibodies that inhibit
      parasite invasion of erythrocytes in vitro. However, after challenge with either
      a homologous or a heterologous strain of parasite, all animals became parasitemic
      and required treatment. The immunization did not induce protection in this animal
      model.

PMID- 8751908
TI  - Decreased interleukin-4 and increased gamma interferon production by peripheral
      blood mononuclear cells of patients with Lyme borreliosis.
AB  - Spontaneous and Borrelia burgdorferi-stimulated proliferation of peripheral blood
      mononuclear cells (PBMCs) and their interleukin-4 (IL-4), gamma interferon (IFN
      gamma), and NO production were measured in 36 patients with second- or third
      stage Lyme borreliosis (LB) and 11 control subjects. Spontaneous proliferation of
      PBMCs was significantly higher (P = 0.0003) in the LB patients than in the
      control subjects. Spontaneous production of IL-4 was significantly lower in
      patients than in control subjects (P = 0.0007), but spontaneous production of IFN
      gamma was slightly higher in patients. The proliferative response of PBMCs to
      stimulation with B. burgdorferi was significantly higher (P = 0.01) in patients.
      The B. burgdorferi-induced production of IFN-gamma (P = 0.002) was also
      significantly higher in patients. The spontaneous and B. burgdorferi-induced
      production of NO showed no significant difference between patients and control
      subjects. These findings indicate that the activation of PBMCs in patients with
      late LB is enhanced in vivo. Furthermore, the production of IL-4 is effectively
      suppressed spontaneously, whereas the production of IFN-gamma by PBMCs is
      slightly increased spontaneously and significantly enhanced during stimulation
      with B. burgdorferi in vitro. The "spontaneous" or disease-induced alterations in
      cytokine levels of patients, in this case suppression of a Th2-type cytokine
      production and activation of a Th1-type cytokine production, may contribute to
      the pathogenesis of LB.

PMID- 8751909
TI  - Porphyromonas gingivalis genes isolated by screening for epithelial cell
      attachment.
AB  - Porphyromonas gingivalis is associated with chronic and severe periodontitis in
      adults. P. gingivalis and the other periodontal pathogens colonize and interact
      with gingival epithelial cells, but the genes and molecular mechanisms involved
      are unknown. To dissect the first steps in these interactions, a P. gingivalis
      expression library was screened for clones which bound human oral epithelial
      cells. Insert DNA from the recombinant clones did not contain homology to the P.
      gingivalis fimA gene, encoding fimbrillin, the subunit protein of fimbriae, but
      showed various degrees of homology to certain cysteine protease-hemagglutinin
      genes. The DNA sequence of one insert revealed three putative open reading frames
      which appeared to be in an operon. The relationship between P. gingivalis
      attachment to epithelial cells and the activities identified by the screen is
      discussed.

PMID- 8751910
TI  - CD8 T-cell recognition of macrophages and hepatocytes results in immunity to
      Listeria monocytogenes.
AB  - CD8 T cells are effective mediators of specific immunity to infection by Listeria
      monocytogenes, a bacterial pathogen that initially infects macrophages in the
      spleen and liver and subsequently spreads to hepatocytes and unidentified
      parenchymal cells in the spleen. To identify the in vivo target cells of L.
      monocytogenes-immune CD8 T cells, adoptive transfer assays were performed with
      bone marrow chimeric or transgenic host mice which had been manipulated to alter
      the major histocompatibility complex molecules expressed on macrophages or
      hepatocytes. L. monocytogenes-immune CD8 T cells mediate significant immunity in
      BDF1-->beta 2 M-/- chimeras, comparable to that seen in unmanipulated BDF1
      recipients. L. monocytogenes-immune CD8 T cells also mediate significant
      antilisterial immunity in parent-->F1 chimeras when the CD8 T cells are syngeneic
      with the bone marrow donor. These data demonstrate that bone marrow-derived
      macrophages are major targets for L. monocytogenes-immune CD8 T cells in adoptive
      transfer assays. Interestingly, significant immunity was observed in parent-->F1
      chimeras when the L. monocytogenes-immune CD8 T cells were not syngeneic with the
      bone marrow donor, suggesting that recognition of Listeria-infected non-bone
      marrow-derived cells such as hepatocytes may also occur in vivo. Consistent with
      this possibility, H-2Kb-restricted CD8 T cells specific for the listeriolysin O
      molecule mediate significant immunity in the liver, but not the spleen, in
      transgenic mice expressing H-2Kb only on hepatocytes. In addition, Listeria
      specific CD8 T cells lyse Listeria-infected hepatocyte-like cells in vitro. Thus,
      Listeria-infected hepatocytes can be recognized by CD8 T cells in vivo and in
      vitro.

PMID- 8751911
TI  - Tolerance to appetite suppression induced by peptidoglycan.
AB  - Physiologically realistic peptidoglycan (PG) fragments, derived from Neisseria
      gonorrhoeae, were shown previously to dose-dependently suppress food consumption
      and body weight gain in rats following single intraperitoneal injections. The
      present study, examining the effects of repeated daily injection of PG, provides
      additional support to our underlying hypothesis, i.e., that soluble PG fragments
      contribute to the loss of appetite commonly associated with bacterial infections.
      An initial intraperitoneal injection of purified, soluble, macromolecular,
      extensively O-acetylated PG fragments (S-O-PG) (240 micrograms/kg of body weight)
      decreased overnight food consumption in male Lewis rats (150 g) by approximately
      35% relative to animals receiving diluent alone (P < 0.05). However, subsequent
      daily injections of S-O-PG resulted in progressively smaller effects on food
      consumption until, by the fourth day, rats were completely nonresponsive
      (tolerant) to S-O-PG-induced hypophagia. Rats that developed tolerance to the
      effects of S-O-PG on appetite were also tolerant to three other known hypophagic
      agents, lipopolysaccharide (LPS), muramyl dipeptide, and interleukin-1, when
      challenged one day after establishment of S-O-PG tolerance. Similarly, rats
      developed tolerance to repeated injections of muramyl dipeptide or LPS and were
      cross-tolerant to S-O-PG when challenged 1 day later. However, 30 days after
      establishment of S-O-PG tolerance, rats remained nonresponsive to S-O-PG but
      regained full responsiveness to LPS-mediated hypophagia. Thus, at least two
      mechanisms of tolerance to S-O-PG hypophagia exist: an early tolerance which is
      nonspecific and a late tolerance which is specific for S-O-PG. Late, but not
      early, tolerance to S-O-PG-mediated suppression of appetite was associated with
      an increase in specific anti-PG antibody activity as measured in an enzyme-linked
      immunosorbent assay.

PMID- 8751912
TI  - Novel pathogenic mechanism of microbial metalloproteinases: liberation of
      membrane-anchored molecules in biologically active form exemplified by studies
      with the human interleukin-6 receptor.
AB  - Certain membrane-anchored proteins, including several cytokines and cytokine
      receptors, can be released into cell supernatants through the action of
      endogenous membrane-bound metalloproteinases. The shed molecules are then able to
      fulfill various biological functions; for example, soluble interleukin-6 receptor
      (sIL-6R) can bind to bystander cells, rendering these cells sensitive to the
      action of IL-6. Using IL-6R as a model substrate, we report that the
      metalloproteinase from Serratia marcescens mimics the action of the endogenous
      shedding proteinase. Treatment of human monocytes with the bacterial protease led
      to a rapid release of sIL-6R into the supernatant. This effect was inhibitable
      with TAPI [N-(D,L-[2-(hydroxyaminocarbonyl)methyl]-4-methylpentanoyl) L-3-(2'
      naphthyl)-alanyl-L-alanine, 2-aminoethyl amide], a specific inhibitor of the
      membrane-bound intrinsic metalloproteinase, but not with other conventional
      proteinase inhibitors. sIL-6R-liberating activity was also detected in culture
      supernatants of Staphylococcus aureus, Pseudomonas aeruginosa, and Listeria
      monocytogenes, organisms that are known to produce metalloproteinases. sIL-6R
      released through the action of S. marcescens metalloproteinase retained
      biological activity and rendered IL-6-unresponsive human hepatoma cells sensitive
      to stimulation with IL-6. This was shown by Northern (RNA) blot detection of
      haptoglobin mRNA and by quantitative measurements of de novo-synthesized
      haptoglobin in cell supernatants. Analysis of immunoprecipitated, radiolabeled
      sIL-6R revealed that the bacterial protease cleaved IL-6R at a site distinct from
      that utilized by the endogenous protease. These studies show that membrane
      anchored proteins can be released in active form through cleavage at multiple
      sites, and they uncover a novel mechanism via which microbial proteases possibly
      provoke long-range biological effects in the host organism.

PMID- 8751913
TI  - Characterization of a P1-deficient strain of Streptococcus mutans that expresses
      the SpaA protein of Streptococcus sobrinus.
AB  - The Streptococcus sobrinus SpaA protein and the Streptococcus mutans P1 protein
      share 66% sequence homology at the amino acid level. To determine if the SpaA
      protein can be expressed in S. mutans and functionally replace the P1 protein,
      the spaA gene of S. sobrinus 6715 was isolated from plasmid pX1303 and inserted
      into the Escherichia coli-Streptococcus shuttle vector pVA838. The resulting
      plasmid pX1600 was transformed into the P1-deficient strain S. mutans 834 that
      has defects in saliva-mediated aggregation and in the ability to adhere to saliva
      coated hydroxyapatite surfaces. Western blot (immunoblot) analysis of cellular
      protein fractions of S. mutans 834 (pX1600) detected in mutanolysin-solubilized
      cell walls a major protein of 210 kDa with an electrophoretic mobility similar to
      that of S. sobrinus SpaA protein and a minor 210-kDa protein and a major 64-kDa
      protein in the extracellular protein fraction. Analysis of virulence traits
      showed that expression of SpaA protein by S. mutans 834(pX1600) cells had
      restored the ability of the S. mutans 834 cells to aggregate in the presence of
      saliva or salivary agglutinin but not to adhere to saliva-coated hydroxyapatite.
      This cell aggregation was inhibited specifically by antisera to S. sobrinus SpaA
      protein. These results indicate that SpaA plays a role in the virulence of S.
      sobrinus by specifically interacting with fluid-phase salivary agglutinin to
      mediate cell aggregation.

PMID- 8751914
TI  - The galactosyl-(alpha 1-4)-galactose-binding adhesin of Streptococcus suis:
      occurrence in strains of different hemagglutination activities and induction of
      opsonic antibodies.
AB  - The occurrence of the galactose-(alpha 1-4)-galactose-specific adhesin in
      Streptococcus suis, a pig and human pathogen causing sepsis, meningitis, and
      other serious infections, was studied. Poly- and monoclonal anti-bodies to the
      purified adhesin, as well as pigeon ovomucoid, a specific probe for the adhesin
      activity, detected one single protein band in extracts of S. suis. The adhesin
      was detected in all 23 strains studied, representing pathogenic serotypes (1, 2,
      4, 5, 7, 8, and nontypeable) and including several weakly hemagglutinating or
      nonhemagglutinating strains and phase variants. The amount of adhesin detected
      was not correlated with the hemagglutination activity of the intact bacteria.
      Extraction of cells showing no binding of pigeon ovomucoid by ultrasonic
      treatment resulted in extracts with pigeon ovomucoid binding activity, suggesting
      that the adhesin was not accessible to the probe on the intact cells. Analysis of
      the amount of capsular polysaccharide revealed an inverse relationship between
      the hemagglutination activity and expression of capsular polysaccharide, thus
      suggesting a factor influencing adhesin accessibility. The purified adhesin was
      highly immunogenic and induced in preliminary experiments bactericidal activity
      in mice. Thus, the adhesin, with its specific binding mechanism to host cells and
      a proposed pathogenic role, is widely expressed among strains of different
      serotypes and therefore appears to represent a novel promising candidate for the
      development of a vaccine against S. suis.

PMID- 8751915
TI  - DNA sequence analysis and restriction fragment length polymorphisms of the P1
      gene of Haemophilus influenzae biogroup aegyptius associated with Brazilian
      purpuric fever.
AB  - Brazilian purpuric fever (BPF) is a fulminant pediatric disease caused by
      specific strains of Haemophilus influenzae biogroup aegyptius. A conserved
      epitope on the P1 protein of strains of H. influenzae biogroup aegyptius is seen
      on most virulent isolates. The P1 protein from a Brazilian case-clone strain of
      H. influenzae biogroup aegyptius was analyzed by cloning and sequencing the gene.
      Three major variable regions are present within the P1 gene of the BPF clone in
      an architecture similar to that of the previously sequenced P1 genes from H.
      influenzae. The DNA sequence data of the P1 gene provided information for
      restriction fragment length polymorphism analyses among strains of H. influenzae
      biogroup aegyptius. Using PCR for amplification of the P1 gene, we found that
      AlwI restriction of this gene allowed for a highly accurate segregation of
      virulent strains of H. influenzae biogroup aegyptius associated with BPF. The
      strong association of virulent phenotypes with specific AlwI restriction patterns
      of the P1 gene provides a basis for the convenient and accurate identification of
      strains of H. influenzae biogroup aegyptius which cause BPF.

PMID- 8751916
TI  - Persistent hepatitis and enterocolitis in germfree mice infected with
      Helicobacter hepaticus.
AB  - Helicobacter hepaticus has been associated with naturally occurring hepatitis in
      certain inbred strains of mice, and in A/JCr mice it has been linked to the
      development of hepatic adenomas and adenocarcinomas. H. hepaticus was orally
      inoculated into 30 axenic, outbred female mice, and the mice were studied
      longitudinally to fulfill Koch's postulates and to ascertain the pathogenic
      potential of the organism under defined germfree conditions. Ten cage contact
      mice were also housed in the same germfree isolator to study transmission
      patterns, and 10 germfree mice were maintained in separate isolators as controls.
      Mice serially euthanized from 3 weeks through 24 months postinoculation (p.i.)
      were surveyed by culture and PCR for H. hepaticus in liver and intestinal
      tissues. Tissues were analyzed for histopathological changes, and sera were
      assayed for the presence of immunoglobulin G antibody to H. hepaticus and changes
      in the liver enzyme alanine aminotransferase. Inoculated mice and cage contact
      mice were persistently infected with H. hepaticus as identified by culture and
      PCR, in both the intestine and, less frequently, the liver, for the duration of
      the 2-year study. Animals developed persistent chronic hepatitis, and in some
      animals enterocolitis was noted. Hepatocellular carcinoma was diagnosed in one H.
      hepaticus-infected mouse. The level of H. hepaticus serum antibody was highest in
      experimentally infected mice at 12 to 18 months p.i.; this corresponded in
      general to the time interval when the highest levels of alanine aminotransferase
      were recorded. Although cage contact mice became persistently infected with H.
      hepaticus, lesions were less severe and the levels of serological biomarkers
      utilized in the study were lower. The H. hepaticus-infected mouse will provide an
      ideal model to study putative bacterial virulence determinants and how they
      interact with the host to induce chronic inflammation and tumorigenesis.

PMID- 8751917
TI  - Inhibition of human peripheral blood mononuclear cell proliferative response by
      glycosphingolipids from metacestodes of Echinococcus multilocularis.
AB  - The effect on human peripheral blood mononuclear cells (PBMCs) of neutral
      glycosphingolipids extracted from metacestodes of the parasite Echinococcus
      multilocularis was investigated. Neutral glycosphingolipids inhibited
      [3H]thymidine uptake by human PBMCs upon stimulation by mitogens such as
      phytohemagglutinin A and pokeweed mitogen or by allogeneic Burkitt B cells. This
      effect was dose dependent and was related to a decrease in interleukin 2 (IL-2)
      synthesis, the expression of IL-2 receptors (CD25) being unmodified. Addition of
      exogenous recombinant IL-2 restored the cell proliferation. Partial inhibition of
      immunoglobulin G (IgG), IgA, and IgM synthesis was observed in the supernatant of
      cell culture in association with the inhibitory effect. Identification of active
      subfractions contained in the neutral glycosphingolipid fraction was also studied
      in relation to cell viability. The free ceramide fraction had an inhibitory
      effect, in part related to cell lysis, particularly at high concentration, while
      the monogalactosylceramides had a paradoxical effect: as an activator at low
      concentrations and as an inhibitor at high concentrations, with limited cell
      survival. The immunogenic neutral glycosphingolipids containing at least two
      carbohydrate residues, all having a structure based on Gal beta 1-->6Gal, were
      inhibitors of PBMC proliferation and showed good cell survival. These results
      suggest that parasite neutral glycosphingolipids may play an immunologically
      relevant role in alveolar hydatid disease.

PMID- 8751919
TI  - Characterization of a novel hemagglutinin of diarrhea-associated Escherichia coli
      that has characteristics of diffusely adhering E. coli and enteroaggregative E.
      coli.
AB  - Escherichia coli 73-1 (serotype O73:H33) and 5-2 (serotype O89:H-) isolated from
      patients with diarrhea adhered to tissue culture cells (HeLa and HEp-2) as well
      as coverslips (plastic and glass) in a diffuse pattern. Adherence of strain 73-1
      was mediated by a 110-kbp plasmid designated pEDA1 and correlated with D-mannose
      resistant hemagglutinin (MRHA) detected with bovine, sheep, or human
      erythrocytes. The MRHA region was duplicated on pEDA1 and mediated the production
      of the 57-kDa outer membrane protein whose N-terminal amino acid sequence was
      hydrophobic. In accordance with MRHA and adherence, the 57-kDa outer membrane
      protein was observed best at 37 degrees C and to a lesser extent at 25 degrees C.
      In human intestine, adherence to mucus and colonic epithelium was obvious. No
      detectable pili were observed. The enteroaggregative E. coli heat-stable
      enterotoxin 1 (EAST1) gene, whose nucleotide sequence was 99.1% homologous to
      that of enteroaggregative E. coli, was present adjacent to the MRHA region on
      pEDA1. Strain 5-2 also exhibited MRHA activities and adherence and had sequences
      corresponding to those of the MRHA region and EAST1 gene. The data suggest that
      strain 73-1 (and strain 5-2), which has characteristics of both diffusely
      adhering E. coli and enteroaggregative E. coli, possesses a novel hemagglutinin
      associated with diffuse adherence.

PMID- 8751918
TI  - Porcine 987P glycolipid receptors on intestinal brush borders and their cognate
      bacterial ligands.
AB  - Certain strains of enterotoxigenic Escherichia coli adhere to piglet intestinal
      epithelial cells by means of the 987P fimbriae. The 987P fimbrial structure
      consists of a helical arrangement of three fimbrial proteins, namely, the major
      subunit FasA and two minor subunits, FasF and FasG. FasG, which is located at the
      fimbrial tip and at various positions along the fimbriae, mediates 987P binding
      to glycoprotein receptors. In this study, we isolated and analyzed the structure
      of piglet glycolipid brush border receptors and characterized their cognate
      ligands on the 987P fimbriae. Two major glycolipid bands recognized by 987P
      fimbrial probes in thin-layer chromatography overlay assays were further purified
      by high-performance thin-layer chromatography and shown to comigrate with control
      galactosylceramide containing hydroxylated fatty acids and with sulfatide. Their
      structures were confirmed by fast atom bombardment mass spectrometry, which
      detected homologous series of ceramide monohexoside and sulfatide with
      hydroxylated fatty acyl chains ranging from h16:0 to h24:0. Assembled 987P
      fimbriae, pre- and postassembly dissociated fimbrial subunits, and Fab fragments
      of specific anti-FasG, -FasF, and -FasA were used to inhibit 987P-mediated
      bacterial binding to the two identified piglet glycolipids and corresponding
      isoreceptor controls. Only assembled fimbriae and anti-FasG Fab fragments were
      significantly able to inhibit bacterial binding to sulfatide, indicating that in
      addition to glycoproteins, FasG recognizes a specific glycolipid of piglet brush
      borders. In contrast, only anti-FasA Fab fragments were significantly able to
      inhibit bacterial binding to galactosylceramide with hydroxylated fatty acids and
      piglet hydroxylated ceramide monohexoside, indicating that FasA may determine a
      third type of ligand-receptor interaction in the piglet intestines. Since these
      bacterial adhesins recognize their respective glycolipid receptors only after
      being assembled in their final fimbrial quaternary structure, adhesin binding may
      involve cooperative interactions and the subunits by themselves may have very low
      binding affinities. Alternatively, conformation-sensitive domains of these
      subunits present in the assembled fimbriae may be required for glycolipid
      binding.

PMID- 8751920
TI  - Identification of an outer membrane protein involved in utilization of hemoglobin
      haptoglobin complexes by nontypeable Haemophilus influenzae.
AB  - A recombinant plasmid containing a 6.5-kb fragment of nontypeable Haemophilus
      influenzae (NTHI) chromosomal DNA was shown to confer a hemoglobin-haptoglobin
      binding phenotype on Escherichia coli. Use of a mini-Tn10kan transposon for
      random insertion mutagenesis of this recombinant plasmid allowed localization of
      the NTHI DNA responsible for this hemoglobin-haptoglobin-binding phenotype to a
      3.5-kb PstI-XhoI fragment within the 6.5-kb NTHI DNA insert. When this
      mutagenized NTHI DNA fragment was used to transform the wild-type NTHI strain,
      the resultant kanamycin-resistant mutant exhibited significantly decreased
      abilities to bind hemoglobin-haptoglobin and utilize it as a source of heme for
      aerobic growth in vitro. This mutant also lacked expression of a 115-kDa outer
      membrane protein that was present in the wild-type parent strain. Transformation
      of this mutant with wild-type NTHI chromosomal DNA restored the abilities to bind
      and utilize hemoglobin-haptoglobin and to express the 115-kDa outer membrane
      protein. Nucleotide sequence analysis of the relevant NTHI DNA revealed the
      presence of a gene, designated hhuA, that encoded a predicted 117,145-Da protein.
      The HhuA protein exhibited features typical of a TonB-dependent outer membrane
      receptor and had significant identity with the hemoglobin receptors of both
      Haemophilus ducreyi and Neisseria meningitidis.

PMID- 8751921
TI  - The late chlamydial inclusion membrane is not derived from the endocytic pathway
      and is relatively deficient in host proteins.
AB  - Chlamydiae are obligate intracellular parasites which multiply within infected
      cells in a membrane-bound structure termed an inclusion. Newly internalized
      bacteria are surrounded by host plasma membrane; however, the source of membrane
      for the expansion of the inclusion is unknown. To determine if the membrane for
      the mature inclusion was derived by fusion with cellular organelles, we stained
      infected cells with fluorescent or electron-dense markers specific for organelles
      and examined inclusions for those markers. We observed no evidence for the
      presence of endoplasmic reticulum, Golgi, late endosomal, or lysosomal proteins
      in the inclusion. These data suggest that the expansion of the inclusion
      membrane, beginning 24 h postinoculation, does not occur by the addition of host
      proteins resulting from either de novo host synthesis or by fusion with
      preexisting membranes. To determine the source of the expanding inclusion
      membrane, antibodies were produced against isolated membranes from Chlamydia
      infected mouse cells. The antibodies were demonstrated to be solely against
      Chlamydia-specified proteins by both immunoprecipitation of [35S]methionine
      labeled extracts and Western blotting (immunoblotting). Techniques were used to
      semipermeabilize Chlamydia-infected cells without disrupting the permeability of
      the inclusion, allowing antibodies access to the outer surface of the inclusion
      membrane. Immunofluorescent staining demonstrated a ring-like fluorescence around
      inclusions in semipermeabilized cells, whereas Triton X-100-permeabilized cells
      showed staining throughout the inclusion. These studies demonstrate that the
      inclusion membrane is made up, in part, of Chlamydia-specified proteins and not
      of existing host membrane proteins.

PMID- 8751922
TI  - Elimination of the listeriolysin O-directed immune response by conservative
      alteration of the immunodominant listeriolysin O amino acid 91 to 99 epitope.
AB  - A major H2-Kd-presented epitope for antilisterial cytotoxic T lymphocytes (CTLs)
      is the nanomer peptide which corresponds to the amino acid 91 to 99 (aa91-99)
      sequence from listeriolysin O (LLO). Although the LLO sequence contains at least
      five additional nanomer peptides which also satisfy the H2-Kd binding motif, aa91
      99 is the only LLO-derived target peptide that is recognized by antilisterial
      CTLs following infection of BALB/c mice with Listeria monocytogenes. In order to
      investigate further the immunodominance of the LLO aa91-99 epitope following
      endogenous processing of LLO, we introduced a point mutation in hly (the gene for
      LLO) which results in a conservative Y-to-F substitution for the anchor residue
      at position 2 within the aa91-99 sequence. This "92F" L. monocytogenes mutant
      produces biologically active LLO and is phenotypically indistinct from wild-type
      L. monocytogenes in terms of intracellular growth in vitro and virulence in vivo.
      BALB/c mice actively immunized with the 92F L. monocytogenes mutant are protected
      against challenge with wild-type L. monocytogenes. Antilisterial CTLs from mice
      immunized with the 92F mutant lyse targets infected with L. monocytogenes;
      however, these CTLs do not lyse target cells pulsed with either the LLO aa91-99
      peptide, other LLO-derived peptides which satisfy the H2-Kd binding motif, or a
      peptide corresponding to the LLO aa91-92F-99 sequence. Target cells pulsed with
      the LLO aa91-92F-99 peptide are, however, lysed by wild-type LLO aa91-99-specific
      cytotoxic cells. Thus, a conservative amino acid change in the first anchor
      residue of the immunodominant aa91-99 sequence of LLO eliminates the induction of
      the cytotoxic cell response to this epitope as well as to any of the other
      candidate LLO-derived peptides which fit the H2-Kd binding motif. The lack of
      anti-LLO-specific CTLs following immunization with the 92F mutant does not
      appear, however, to influence the protective antilisterial immune response.

PMID- 8751923
TI  - Two pathogenicity islands in uropathogenic Escherichia coli J96: cosmid cloning
      and sample sequencing.
AB  - Many of the virulence genes of pathogenic strains of Escherichia coli are carried
      in large multigene chromosomal segments called pathogenicity islands (PAIs) that
      are absent from normal fecal and laboratory K-12 strains of this bacterium. We
      are studying PAIs in order to better understand factors that govern virulence and
      to assess how such DNA segments are gained or lost during evolution. The
      isolation and sample sequencing of a set of 11 cosmid clones that cover all of
      one and much of a second large PAI in the uropathogenic E. coli J96 are
      described. These PAIs were mapped to the 64- and 94-min regions of the E. coli K
      12 chromosome, which differ from the locations of three PAIs identified in other
      pathogenic E. coli strains. Analysis of the junction sequences with E. coli K-12
      like DNAs showed that the insert at 94 min is within the 3' end of a
      phenylalanine tRNA gene, pheR, and is flanked by a 135-bp imperfect direct
      repeat. Analysis of the one junction recovered from the insert at 64 min
      indicated that it lies near another tRNA gene, pheV. To identify possible genes
      unique to these PAIs, 100 independent subclones of the cosmids were made by PstI
      digestion and ligation into a pBS+ plasmid and used in one-pass sample DNA
      sequencing from primer binding sites at the cloning site in the vector DNA.
      Database searches of the J96 PAI-specific sequences identified numerous instances
      in which the cloned DNAs shared significant sequence similarities to adhesins,
      toxins, and other virulence determinants of diverse pathogens. Several likely
      insertion sequence elements (IS100, IS630, and IS911) and conjugative R1 plasmid
      and P4 phage genes were also found. We propose that such mobile genetic elements
      may have facilitated the spread of virulence determinants within PAIs among
      bacteria.

PMID- 8751924
TI  - Cloning, nucleotide sequence, and expression of the Brucella melitensis omp31
      gene coding for an immunogenic major outer membrane protein.
AB  - The gene coding for the major outer membrane protein (OMP) of 31 to 34 kDa, now
      designated Omp31, of Brucella melitensis 16M was cloned and sequenced. A B.
      melitensis 16M genomic library was constructed in lambda GEM-12 XhoI half-site
      arms, and recombinant phages expressing omp31 were identified by using the anti
      Omp31 monoclonal antibody (MAb) A59/10F09/G10. Subcloning of insert DNA from a
      positive phage into pGEM-7Zf allowed the selection of a plasmid bearing a 4.4-kb
      EcoRI fragment that seemed to contain the entire omp31 gene under control of its
      own promoter. omp31 was localized within a region of the EcoRI insert of
      approximately 1.1 kb. Sequencing of this region revealed an open reading frame of
      720 bp encoding a protein of 240 amino acids and a predicted molecular mass of
      25,307 Da. Cleavage of the first 19 amino acids, showing typical features of
      signal peptides for protein export, leaves a mature protein of 221 amino acids
      with a predicted molecular mass of 23,412 Da. The predicted amino acid sequence
      of B. melitensis 16M Omp31 showed 35.2% identity with the RopB OMP of Rhizobium
      leguminosarum bv. viciae 248 and 34.3% identity with Omp25 of B. abortus 544. As
      in Brucella spp., Omp31 was located in the outer membrane of recombinant
      Escherichia coli, but its reported peptidoglycan association in Brucella cells
      was not detected in E. coli. The ability of Omp31 to form oligomers resistant to
      sodium dodecyl sulfate denaturation at low temperatures, a characteristic
      described for several bacterial porins, was observed in both B. melitensis and
      recombinant E. coli. The epitope recognized by the anti-Omp31 MAb A59/10F09/G10,
      for which a protective activity has been suggested, has been delimited to a
      region of 36 amino acids of Omp31 covering the most hydrophilic part of the
      protein. The availability of recombinant Omp31 and the identification of the
      antigenic determinant recognized by MAb A59/10F09/G10 will allow the evaluation
      of their potential protective activity and their potential for the development of
      subcellular vaccines against brucellosis.

PMID- 8751925
TI  - Binding of resting platelets to Candida albicans germ tubes.
AB  - The binding of resting platelets to Candida albicans germ tubes was studied by
      means of an affinity column in which germ tubes were physically immobilized.
      Adhesion of platelets to the column was dependent on both the germ tube
      concentration and the number of platelets applied. It was found that the
      interaction of C. albicans germ tubes with platelets is specific and should be
      mediated by a fungal protein receptor. The results obtained by scanning electron
      microscopy confirmed that resting platelets can fix directly onto germ tubes. In
      addition, this study showed that attachment of platelets onto C. albicans is
      associated with morphological changes. Platelets lost their discoid shape, became
      globular, generated spikes or pseudopods, and then flattened on the yeast cells.

PMID- 8751926
TI  - Staphylocidal action of thrombin-induced platelet microbicidal protein is
      influenced by microenvironment and target cell growth phase.
AB  - Thrombin-induced platelet microbicidal protein (tPMP) is a small, cationic
      peptide released from rabbit platelets following exposure to thrombin in vitro.
      This peptide exerts potent in vitro microbicidal activity against a broad
      spectrum of bloodstream pathogens, including Staphylococcus aureus. It is known
      that the microbicidal actions of other cationic antimicrobial peptides (e.g.,
      neutrophil defensins) are influenced by environmental factors and target cell
      growth phase. However, whether these parameters affect tPMP microbicidal activity
      has not been studied. Thus, we assessed the in vitro bactericidal activity of
      tPMP against two tPMP-susceptible strains, Bacillus subtilis ATCC 6633 and S.
      aureus 502A, in various target cell growth phases or under various
      microenvironmental conditions. The conditions studied included differing
      bacterial growth phase (logarithmic versus stationary), temperature (range, 4 to
      42 degrees C), pH (range, 4.5 to 8.5), cationicity (range, 0.1 mM to 2 M),
      anionicity (range, 0.08 to 5 microM), and neutral carbohydrates ranging in
      molecular weight (MW) from 180 to 37,700 (range, 50 to 500 mM) as well as rabbit
      platelet-free plasma and serum. tPMP staphylocidal activity was greater against
      logarithmic- than stationary-phase cells. tPMP bactericidal activity against both
      B. subtilis and S. aureus was directly correlated with temperature and pH, with
      microbicidal activity exhibited near the physiological range (37 to 42 degrees C
      and pH 7.2 to 8.5, respectively). The presence of cations (Na+, K+, Ca2+, and
      Mg2+) decreased tPMP bactericidal activity in a time- and concentration-dependent
      manner, with complete inhibition at monovalent or divalent cation concentrations
      of > or = 250 or > or = 10 mM, respectively. Staphylocidal activity of tPMP was
      also inhibited by the polyanions polyanetholsulfonic acid and polyaspartic acid,
      at 0.1 and 0.4 microM, respectively. Coincident exposure with low-MW
      carbohydrates (glucose, sucrose, and melezitose) did not affect tPMP
      staphylocidal activity. However, higher-MW carbohydrates (raffinose and dextrans)
      decreased tPMP activity in a manner directly proportional to their concentration
      and MW. Solute-mediated inhibition of tPMP bactericidal activity was independent
      of solute osmolality but directly related to the duration of tPMP-solute
      coexposure. tPMP enhanced the staphylocidal activities of platelet-free plasma
      and heat-inactivated serum, while the activity of normal serum was not affected.
      These collective observations suggest that tPMP retains antimicrobial activities
      under physiological conditions which are likely to be relevant to host defense in
      vivo.

PMID- 8751927
TI  - Analysis of a genomic DNA expression library of Mycobacterium tuberculosis using
      tuberculosis patient sera: evidence for modulation of host immune response.
AB  - DNA obtained from a human sputum isolate of Mycobacterium tuberculosis, NTI
      64719, which showed extensive dissemination in the guinea pig model resulting in
      a high score for virulence was used to construct an expression library in the
      lambda ZAP vector. The size of DNA inserts in the library ranged from 1 to 3 kb,
      and recombinants represented 60% of the total plaques obtained. When probed with
      pooled serum from chronically infected tuberculosis patients, the library yielded
      176 recombinants with a range of signal intensities. Among these, 93 recombinants
      were classified into 12 groups on the basis of DNA hybridization experiments. The
      polypeptides synthesized by the recombinants were predominantly LacZ fusion
      proteins. Serum obtained from patients who were clinically diagnosed to be in the
      early phase of M. tuberculosis infection was used to probe the 176 recombinants
      obtained. Interestingly, some recombinants that gave very strong signals in the
      original screen did not react with early-phase serum; conversely, other whose
      signals were extremely weak in the original screen gave very intense signals with
      serum from recently infected patients. This indicates the differential nature of
      either the expression of these antigens or the immune response elicited by them
      as a function of disease progression.

PMID- 8751928
TI  - Uptake of Streptococcus pneumoniae by respiratory epithelial cells.
AB  - Although Streptococcus pneumoniae is the leading cause of community-acquired
      pneumonia in humans, the mechanism whereby the organism penetrates lung tissue is
      poorly understood. In the present study we have examined the capacity of
      pneumococci to penetrate A549 cells, a human lung alveolar carcinoma (type II
      pneumocyte) cell line. Not all clinical S. pneumoniae isolates initially tested
      were capable of penetration of the cells, as judged by resistance to
      extracellular antibiotics. The presence of a polysaccharide capsule also
      significantly reduced the capacity to both adhere to and penetrate A549 cells.
      Electron micrographs showed the presence of pneumococci enclosed within vacuoles
      of intact A549 cells, but bacteria were also seen free in the cytoplasm of
      damaged cells. Ongoing bacterial DNA, RNA, or protein synthesis was not essential
      for uptake of pneumococci by A549 cells, and uptake was not diminished by
      pretreatment of the pneumococci with trypsin. However, inhibition of A549
      microfilament assembly with cytochalasin D abolished the phenomenon.

PMID- 8751929
TI  - Immune mechanisms and protective antigens of Vibrio cholerae serogroup O139 as a
      basis for vaccine development.
AB  - We have characterized 11 isolates of Vibrio cholerae O139 Bengal with regard to
      properties deemed to be relevant for development of a vaccine against O139
      cholera. For most strains two colony variants, A and B, which are nonhemolytic
      and hemolytic, respectively, were detected on blood agar. The A and B variants
      were associated with high- and low-level production of soluble hemagglutinin
      protease, respectively. However, on Luria-Bertani agar both types formed opaque
      colonies, which has been shown to be associated with capsule formation.
      Interestingly, under the stationary tube-shaken flask culture conditions in yeast
      extract-peptone water medium which were used to stimulate the production of
      cholera toxin (CT) and toxin-coregulated pili, B variants constitutively produced
      CT and TcpA, two ToxR-regulated proteins, at 28 and 37 degrees C, whereas the
      production of these proteins by A variants was downregulated at the higher
      temperature. One of the strains, 4260B, having a well-exposed O antigen and
      capsule and the capacity to produce large amounts of TcpA, CT, and mannose
      sensitive hemagglutinin pili but minimal amounts of the proteolytic soluble
      hemagglutinin, was selected to produce antibacterial antisera and as a challenge
      strain in protection studies using the rabbit ileal loop model. Rabbit antisera
      to live, heat-killed, or formalin-killed O139 vibrios or to purified O139
      lipopoly-saccharide (LPS) as well as monoclonal antibodies (MAbs) to O139 LPS
      agglutinated all O139 isolates. However, when A and B variants of strain 4260
      were tested for sensitivity to vibriocidal activity of these antibody
      preparations, only the B variant was killed. All of the antisera against live or
      killed O139 vibrios conferred passive protection against fluid accumulation
      induced by the challenge strain. The protective effects of the antisera were
      correlated to anti-LPS antibody titers rather than to titers against whole
      bacteria that had been grown for toxin-coregulated pilus expression. This
      protection was considerably higher than that conferred by antisera to classical,
      EI Tor, or recombinantly produced (classical) CT or CTB. Furthermore, MAbs to
      O139 LPS and CTB-CT exhibited a strong synergistic protection against O139
      challenge irrespective of the level of sensitivity of challenge strains to O139
      LPS MAbs in vibriocidal assays in vitro.

PMID- 8751930
TI  - Attenuated Salmonella vaccine-induced suppression of murine spleen cell responses
      to mitogen is mediated by macrophage nitric oxide: quantitative aspects.
AB  - Previous reports from our laboratory have shown that 7 days after infection of
      C3HeB/FeJ mice with an attenuated strain of Salmonella typhimurium, there is
      profound suppression of responses to B- and T-cell mitogens and suppression of
      the capacity of spleen cells to mount a primary, in vitro plaque-forming-cell
      (PFC) response to sheep erythrocytes. Inhibition of the PFC response was shown to
      be mediated by nitric oxide (NO), as NG-monomethyl-L-arginine (NMMA) gave
      complete reversal of suppression. The experiments reported here examined the role
      of NO in suppression of the response to the mitogen concanavalin A (ConA). In
      contrast to the PFC system, it was found that addition of NMMA to ConA-stimulated
      immune spleen cells resulted in less than 20% reversal of suppression. However,
      addition to NMMA resulted in a 50% reversal of suppression in cocultures of
      immune and normal spleen cells at a ratio of 1:4. A complete restoration of ConA
      induced responses was achieved in cocultures incubated in medium containing a
      reduced concentration of L-arginine plus 1.25 mM NMMA. Investigation of why NMMA
      alone was not 100% effective in reversing suppression showed that addition of
      ConA significantly augmented production of nitrite and gamma interferon (IFN
      gamma) in cocultures containing immune cells. Addition of anti-IFN-gamma reduced
      nitrite levels in the cultures, although results with the combination of anti-IFN
      gamma and NMMA were not significantly better than results with NMMA alone. These
      findings suggest that suppression in cultures stimulated with ConA is difficult
      to reverse completely with NMMA alone because of an overproduction of NO, which
      can be offset by either reducing the L-arginine concentration or blocking IFN
      gamma. The quantitative relationship between nitrite levels and suppression in
      cocultures was examined. It was found that suppression did not correlate directly
      with the nitrite concentration but rather with the log10 of the nitrite
      concentration. Nitrite levels above 15 microM gave almost complete suppression,
      and levels between 1 and 10 microM gave a wide range of suppression. These
      results strongly support NO as the suppressor factor in Salmonella-induced
      immunosuppression of responses to ConA and, by inference, suppression of
      responses to mitogens induced by other microbes. The results show that
      involvement of NO cannot always be demonstrated by simple addition of NMMA to
      suppressed mitogen-stimulated spleen cell cultures.

PMID- 8751931
TI  - T lymphocytes in the murine vaginal mucosa are phenotypically distinct from those
      in the periphery.
AB  - The results from both clinical studies of women with recurrent vulvovaginal
      candidiasis and a murine model of experimental vaginitis indicate that systemic
      cell-mediated immunity may not represent a dominant host defense mechanism
      against vaginal infections by Candida albicans. Recent experimental evidence
      indicates the presence of local vaginal immune reactivity against C. albicans.
      The present study was designed to examine T-lymphocyte subpopulations in the
      vaginal mucosae of naive CBA/J mice. Vaginal lymphocytes (VL) were isolated by
      collagenase digestion of whole vaginal tissues. Cell populations were identified
      by flow cytometry, and the results were compared with those for both lymph node
      cells (LNC) and peripheral blood lymphocytes (PBL). The results of flow cytometry
      showed that 45% +/- 10% of lymphocytes in the vaginal mucosa are CD3+ compared
      with 75% +/- 5% in LNC and 50% +/- 5% in PBL. The majority (85%) of CD3+ VL are
      CD4+ and express the alpha/beta T-cell receptor (TCR), similar to the results for
      LNC and PBL. In contrast to LNC and PBL, VL contain a significantly higher
      percentage (15 to 20%) of gamma/delta TCR+ cells, 80% or more of which appear to
      express CD4. In addition, while CD4-CD8 cell ratios in LNC and PBL were 3:1 and
      6:1, respectively, only 1% of VL expressed CD8, resulting in a CD4-CD8 cell ratio
      of > 100:1. Finally, while LNC and PBL recognized two epitope-distinct (GK 1.5
      and 2B6) anti-CD4 antibodies, VL recognized only 2B6 anti-CD4 antibodies. Further
      analysis of VL showed that Thy-1 cells, but not CD4 cells, were reduced after
      intravaginal injection of complement-fixing anti-Thy-1.2 and GK 1.5 anti-CD4
      antibodies, respectively. Taken together, these data suggest that T lymphocytes
      in the vaginal mucosae of mice are phenotypically distinct from those in the
      periphery and that CD4+ VL have an uncharacteristic or atypical expression of the
      CD4 receptor.

PMID- 8751932
TI  - Gastric invasion by Trypanosoma cruzi and induction of protective mucosal immune
      responses.
AB  - Trypanosoma cruzi is an intracellular parasite transmitted from a reduviid insect
      vector to humans by exposure of mucosal surfaces to infected insect excreta. We
      have used an oral challenge murine model that mimics vector-borne transmission to
      study T. cruzi mucosal infection. Although gastric secretions have microbicidal
      activity against most infectious pathogens, we demonstrate that T. cruzi can
      invade and replicate in the gastric mucosal epithelium. In addition, gastric
      mucosal invasion appears to be the unique portal of entry for systemic T. cruzi
      infection after oral challenge. The mucosal immune responses stimulated by T.
      cruzi gastric infection are protective against a secondary mucosal parasite
      challenge. This protective mucosal immunity is associated with increased numbers
      of lymphocytes that secrete parasite-specific immunoglobulin A. Our results
      document the first example of systemic microbial invasion through gastric mucosa
      and suggest the feasibility of a mucosal vaccine designed to prevent infection
      with this important human pathogen.

PMID- 8751933
TI  - Role of lipopolysaccharide in colonization of the mouse intestine by Salmonella
      typhimurium studied by in situ hybridization.
AB  - An avirulent, streptomycin-resistant Salmonella typhimurium strain, SL5319, and
      its lipopolysaccharide (LPS)-deficient mutant strain, SL5325, differ in their
      ability to colonize the large intestines of streptomycin-treated mice. When fed
      to mice independently, the strains colonize equally well, but when fed together,
      the LPS-deficient mutant is outcompeted by the wild-type strain during
      establishment in the gut (J.J. Nevola, B.A.D. Stocker, D.C. Laux, and P.S. Cohen,
      Infect. Immun. 50:152-159, 1985). In the present study, the spatial distribution
      in the intestinal mucosal layer of the two strains was visualized by specific
      hybridization to bacterial rRNA in histological sections of mouse colon and
      cecum. The first day after infection, 9.8% of the smooth SL5319 cells observed in
      mucus were found to be associated with the mouse epithelial cells, but three days
      after infection, the corresponding fraction of adhering bacteria was reduced to
      2.1%. The LPS-deficient S. typhimurium strain was confined to the part of the
      mucosal layer closest to the colonic lumen and was not observed to adhere to the
      epithelium either at day 1 or 3 after infection. Quantitative determinations of
      the distance from the S. typhimurium cells to the epithelial wall confirmed that
      the average distance for the rough S. typhimurium SL5325 was much larger than for
      its smooth counterpart, S. typhimurium SL5319. Quantification of the
      hybridization signal from bacteria isolated from the cecal mucus revealed that
      the two strains had the same ribosome concentration, indicating that they have
      the same potential for growth in the intestinal environment. On the basis of
      these observations, we suggest that the better colonization ability of the strain
      carrying wild-type LPS is due to the better abilities to penetrate the intestinal
      mucosal layer and to subsequently bind to the epithelial cells in vivo.

PMID- 8751934
TI  - Group B streptococcal beta-hemolysin expression is associated with injury of lung
      epithelial cells.
AB  - Group B streptococci (GBS) are the leading cause of serious bacterial infection
      in newborns. Early-onset disease is heralded by pneumonia and lung injury, and
      the lung may serve as a portal of entry for GBS into the bloodstream. To examine
      a potential role for GBS beta-hemolysin in lung epithelial injury, five wild-type
      strains varying in beta-hemolysin expression were chosen, along with five
      nonhemolytic (NH) and five hyperhemolytic (HH) variants of these strains derived
      by chemical or transposon mutagenesis. Monolayers of A549 alveolar epithelial
      cells were exposed to log-phase GBS or stabilized hemolysin extracts of GBS
      cultures, and cellular injury was assessed by lactate dehydrogenase (LDH) release
      and trypan blue nuclear staining. Whereas NH strains produced no detectable
      injury beyond baseline (medium alone), hemolysin-producing strains induced LDH
      release from A549 cells in direct correlation to their ability to lyse sheep
      erythrocytes. HH strains were also associated with marked increases in trypan
      blue nuclear staining of A549 monolayers. The extent of LDH release produced by
      HH strains was significantly reduced in the presence of dipalmitoyl
      phosphatidylcholine, a known inhibitor of hemolysin and the major phospholipid
      component of human surfactant. Electron microscopic studies of A549 cell
      monolayers exposed to HH GBS mutants revealed global loss of microvillus
      architecture, disruption of cytoplasmic and nuclear membranes, and marked
      swelling of the cytoplasm and organelles. We conclude that GBS hemolysin
      expression correlates with lung epithelial cell injury and may be important in
      the initial pathogenesis of early-onset disease, particularly when pulmonary
      surfactant is deficient.

PMID- 8751935
TI  - Adhesion of Helicobacter pylori to polarized T84 human intestinal cell monolayers
      is pH dependent.
AB  - Epithelial cells, which form tight polarized monolayers on porous substrates,
      constitute ideal model systems to study bacterial adhesion and invasion. The
      binding of Helicobacter pylori to the apical membrane of T84 cells, an epithelial
      cell line derived from a human colon carcinoma, was assessed biochemically and
      morphologically. Attachment was rapid, and binding remained constant over time,
      with a significant (P < 0.01, Mann-Whitney U test) ca. fourfold increase at pH
      5.4 (76% +/- 22%) compared with pH 7.4 (18% +/- 7%). In contrast, adhesion of
      enteropathogenic Escherichia coli was not enhanced at pH 5.4. The transepithelial
      electrical resistance of the T84 cell monolayers was not affected by pH or by H.
      pylori. Following binding, H. pylori induced a reorganization of the brush border
      as reflected by actin condensation, facilitating the intimate association of the
      bacteria with the apical plasma membrane. H.pylori was not internalized, as shown
      by confocal microscopy. Some bacteria, found in deep invaginations of the apical
      membrane, were probably inaccessible to gentamicin, thus accounting for the
      observed tolerance to the antibiotic. These data provide the first evidence that
      an acidic environment favors Helicobacter adhesion and that binding is followed
      by survival of the survival of the bacteria in pockets of the apical membrane.

PMID- 8751936
TI  - NYVAC-Pf7: a poxvirus-vectored, multiantigen, multistage vaccine candidate for
      Plasmodium falciparum malaria.
AB  - The highly attenuated NYVAC vaccinia virus strain has been utilized to develop a
      multiantigen, multistage vaccine candidate for malaria, a disease that remains a
      serious global health problem and for which no highly effective vaccine exists.
      Genes encoding seven Plasmodium falciparum antigens derived from the sporozoite
      (circumsporozoite protein and sporozoite surface protein 2), liver (liver stage
      antigen 1), blood (merozoite surface protein 1, serine repeat antigen, and apical
      membrane antigen 1), and sexual (25-kDa sexual-stage antigen) stages of the
      parasite life cycle were inserted into a single NYVAC genome to generate NYVAC
      Pf7. Each of the seven antigens was expressed in NYVAC-Pf7-infected culture
      cells, and the genotypic and phenotypic stability of the recombinant virus was
      demonstrated. When inoculated into rhesus monkeys, NYVAC-Pf7 was safe and well
      tolerated. Antibodies that recognize sporozoites, liver, blood, and sexual stages
      of P. falciparum were elicited. Specific antibody responses against four of the
      P.falciparum antigens (circumsporozoite protein, sporozoite surface protein 2,
      merozoite surface protein 1, and 25-kDa sexual-stage antigen) were characterized.
      The results demonstrate that NYVAC-Pf7 is an appropriate candidate vaccine for
      further evaluation in human clinical trials.

PMID- 8751938
TI  - The alpha-hemolysin of Streptococcus gordonii is hydrogen peroxide.
AB  - The alpha-hemolysin of viridans group streptococci, which causes greening of
      intact erythrocytes, is a potential virulence factor as well as an important
      criterion for the laboratory identification of these bacteria; however, it has
      never been purified and characterized. The alpha-hemolysin of Streptococcus
      gordonii CH1 caused characteristic shifts in the A403, A430, A578, and A630 of
      sheep hemoglobin. A spectrophotometric assay was developed and used to monitor
      purification of alpha-hemolysin during extraction in organic solvents and
      separation by reverse-phase high-performance liquid chromatography (HPLC). The
      alpha-hemolysin was identical to hydrogen peroxide with respect to its effects on
      erythrocyte hemoglobin, oxygen-dependent synthesis by streptococci, insensitivity
      to proteases, inactivation by catalase, differential solubility, failure to
      adsorb to ion-exchange chromatography resins, and retention time on a reverse
      phase HPLC column. The amount of hydrogen peroxide present in HPLC-fractionated
      spent culture medium was sufficient to account for all alpha-hemolytic activity
      observed.

PMID- 8751939
TI  - Epitopes recognized by human T lymphocytes in the ROP2 protein antigen of
      Toxoplasma gondii.
AB  - The ROP2 protein of Toxoplasma gondii possesses immunological and biological
      properties which have led to its proposal as a vaccine candidate. To identify
      epitopes recognized by human T cells in the ROP2 antigen, we submitted the
      sequence of this protein to three reported T-cell epitope prediction algorithms.
      Three sequences that were predicted by all three methods were selected (sequences
      197 to 216, 393 to 410, and 501 to 524), and the corresponding peptides were
      synthesized. The peptides were first tested in a proliferation assay with a DPw4
      restricted, ROP2-specific human T-cell clone, and the peptide corresponding to
      residues 197 to 216 was shown to stimulate the T-cell clone. The three peptides
      were further tested in proliferation assays with peripheral blood mononuclear
      cells from a panel of T. gondii-seropositive and -seronegative individuals. We
      found that cells from a high proportion of the seropositive donors (64%)
      recognized at least one of the three peptides. The most frequently recognized
      ones were peptides 197 to 216 (45%) and 501 to 524 (36%). None of the
      seronegative donors responded to any peptide. These results show that the ROP2
      antigen of T. gondii contains T-cell epitopes recognized by a high percentage of
      the immune population and further strengthen its potential as a vaccine
      candidate.

PMID- 8751937
TI  - Activation of human monocytic cells by Treponema pallidum and Borrelia
      burgdorferi lipoproteins and synthetic lipopeptides proceeds via a pathway
      distinct from that of lipopolysaccharide but involves the transcriptional
      activator NF-kappa B.
AB  - There is increasing evidence that lipoproteins of Treponema pallidum and Borrelia
      burgdorferi are key inflammatory mediators during syphilis and Lyme disease. A
      principal objective of the present study was to identify more precisely
      similarities and divergences among lipopolysaccharide (LPS)- and lipoprotein
      lipopeptide-induced immune cell signaling events. Like LPS, purified native B.
      burgdorferi OspA and synthetic analogs of OspA, OspB, and two T. pallidum
      lipoproteins (Tpp47 and Tpp17) all induced NF-kappa B translocation in THP-1
      human monocytoid cells. Acylation of OspA and the synthetic peptides was
      requisite for cell activation. Polymyxin B abrogated only the response to LPS. By
      using 70Z/3-derived pre-B-cell lines either lacking or expressing human CD14 (the
      LPS receptor), it was observed that expression of human CD14 imparted
      responsiveness to LPS but not to OspA or spirochetal lipopeptides (assessed by
      induction of NF-kappa B and expression of surface immunoglobulin M). Finally, the
      biological relevance of the observation that T. pallidum lipoproteins
      lipopeptides induce both NF-kappa B and cytokine production in monocytes was
      supported by the ability of the synthetic analogs to promote human
      immunodeficiency virus replication in chronically infected U1 monocytoid cells;
      these observations also suggest a potential mechanism whereby a syphilitic
      chancre can serve as a cofactor for human immunodeficiency virus transmission.
      The combined data lend additional support to the proposal that spirochetal
      lipoproteins and LPS initiate monocyte activation via different cell surface
      events but that the signaling pathways ultimately converge to produce
      qualitatively similar cellular responses.

PMID- 8751940
TI  - A live (delta aroA) Aeromonas salmonicida vaccine for furunculosis preferentially
      stimulates T-cell responses relative to B-cell responses in rainbow trout
      (Oncorhynchus mykiss).
AB  - We have previously described (L. M. Vaughan, P. R. Smith, and T. J. Foster,
      Infect. Immun. 61:2172-2181, 1993) the construction of a kanamycin-resistant
      aromatic-dependent mutant of Aeromonas salmonicida, the causative agent of
      furunculosis, and its use as a live vaccine. Here we describe the construction of
      an unmarked aroA deletion mutant and examine the nature and magnitude of immune
      responses in rainbow trout (Oncorhynchus mykiss) to this vaccine strain. Good
      proliferative and antibody responses were elicited by using a range of vaccine
      doses from 2 x 10(6) to 2 x 10(9) live bacteria per fish, and a clear vaccine
      dose effect was apparent. A significant positive effect of using live bacteria to
      prime for lymphocyte proliferation and antibody production was apparent. However,
      the problem of directly comparing the vaccine doses of live and killed bacterial
      preparations is discussed, since some replication of live bacteria in vivo is
      expected. Most importantly, the live vaccine preferentially stimulated enhanced T
      cell responsiveness, as evidenced by significantly greater increases in T-cell
      proliferation than in B-cell proliferation, compared with responses by the
      respective cell populations from fish given a killed vaccine. The manner in which
      live vaccines elicit strong cell-mediated immune responses and the relevance to
      fish vaccine design are discussed.

PMID- 8751941
TI  - Correlation of plasmids with infectivity of Borrelia burgdorferi sensu stricto
      type strain B31.
AB  - The correlation of plasmid profiles with infectivity was investigated by using
      five clones of Borrelia burgdorferi sensu stricto strain B31 (ATCC 35210).
      Plasmid profiles were determined by pulsed-field and two-dimensional gel
      electrophoresis. The 50% infectious dose (ID50) in hamsters was determined. The
      ID50 of the clone that possessed a full complement of eight linear and three
      circular plasmids was 10(3) cells. The loss of the 27.5- and 40-kb linear
      plasmids did not decrease the infectivity of these cells. Rather, the loss of the
      27.5-kb linear plasmid was associated with a more disseminated infection. A
      moderate decrease of the ID50 from 10(3) to 10(5) cells correlated with the loss
      of the 9.0-kb circular plasmid and the 27.5-kb linear plasmid. A major loss of
      infectivity (ID50 > 10(3) cells) occurred with cells that lost the 24.7- and 27.5
      kb linear plasmids and the 9.0-kb circular plasmid. A 3.0-kb HindIII fragment of
      the 24.7-kb linear plasmid was used as a probe to determine the presence of the
      homologous sequences in the three genospecies of Lyme disease spirochetes. An
      analysis of 21 infectious strains of B. burgdorferi sensu stricto, B. garinii,
      and B. afzelii revealed a consistent association of infectivity with strains
      possessing a linear plasmid (size range, 24 to 36 kb) that hybridized with the
      HindIII fragment. Western immunoblotting with hamster antisera against infectious
      B31 clone C-3 revealed two proteins with molecular masses of 28 and 43 kDa that
      were absent in the noninfectious B31 clone C-1. Additionally, a 14-kDa protein
      was absent in C-1 but present in infectious clone C-9 as shown by two-dimensional
      polyacrylamide gel electrophoresis.

PMID- 8751942
TI  - Rapid and complete fusion of macrophage lysosomes with phagosomes containing
      Salmonella typhimurium.
AB  - The virulence of Salmonella typhimurium for mice results, in part, from its
      ability to survive after phagocytosis by macrophages. Although it is generally
      agreed that intracellular bacteria persist in membrane-bound phagosomes, there
      remains some question as to whether these phagosomes fuse with macrophage
      lysosomes. This report describes the maturation of phagosomes containing S.
      typhimurium inside mouse bone marrow-derived macrophages. Macrophages were
      infected briefly and incubated for various intervals; then they were examined by
      fluorescence microscopy for colocalization of bacteria with lysosomal markers.
      These markers included LAMP-1, cathepsin L, and fluorescent proteins or dextrans
      preloaded into lysosomes by endocytosis. By all measures, phagosomes containing
      S. typhimurium merged completely with the lysosomal compartment within 20 min of
      phagocytosis. The rate of phagosome-lysosome fusion was similar to the rate for
      phagocytosed latex beads. Phagolysosomes remained accessible to fluid-phase
      probes and contained lysosomal markers for many hours. Moreover, a large
      percentage of the wild-type bacteria that were viable 20 min after infection
      survived longer incubations inside macrophages, indicating that the survivors
      were not a minor subpopulation that avoided phagosome-lysosome fusion. Therefore,
      we conclude that S. typhimurium survives within the lysosomal compartments of
      macrophages.

PMID- 8751944
TI  - The hemagglutinin of Staphylococcus saprophyticus is a major adhesin for
      uroepithelial cells.
AB  - The 160-kDa hemagglutinin of Staphylococcus saprophyticus also serves as a
      fibronectin-binding protein, and the two activities may be present on different
      parts of the molecule. Bacteria expressing the 160-kDa hemagglutinin bound in
      large numbers to histological sections of human ureters, whereas
      nonhemagglutinating bacteria did not bind. Binding was decreased by an antiserum
      to the 160-kDa protein and by a preparation of sheep erythrocyte membranes.
      Fibronectin had no effect. We therefore conclude that binding of S. saprophyticus
      to uroepithelial cells is mediated by the hemagglutinating activity of the 160
      kDa surface protein.

PMID- 8751943
TI  - Invasive phenotype of Trypanosoma cruzi restricted to a population expressing
      trans-sialidase.
AB  - Trypanosoma cruzi expresses a developmentally regulated trans-sialidase
      implicated in the pathogenesis of Chagas' disease. On inhabitation of the
      extracellular milieu of cultured cells by infective trypomastigotes, the enzyme
      is restricted to a small (20 to 30%) population of parasites. The biological
      significance of trans-sialidase expression on this subset, termed TS+, and not on
      the majority (70 to 80%) of morphologically similar trypanosomes, named TS-, is
      unknown. To determine the roles of the TS+ and TS- subsets in T. cruzi invasion,
      we prepared pure populations of TS- and TS+ trypanosomes using magnetic beads
      coated with a monoclonal antibody specific for the tandem repeat unit of the
      trans-sialidase C terminus. After removal of nonadherent TS- trypomastigotes, the
      TS+ trypomastigotes were isolated from the beads by specific elusion with a
      synthetic peptide epitope of the trans-sialidase monoclonal antibody.
      Confirmation of TS+ and TS- phenotypes was obtained by immunofluorescence,
      immunoblotting, and sialidase or sialyl transferase activity measurements. The
      TS+ trypanosomes were highly invasive, as they attached to, penetrated, and
      thrived in cultured mammalian cells much more efficiently than did unfractionated
      parasites. The critical role of the trans-sialidase in invasion was underscored
      by the observation that infection was neutralized by human antibodies to
      transsialidase. What's more, the TS- parasites, in sharp contrast to their TS+
      counterparts, were extremely inefficient in invading epithelial cells and
      fibroblasts. Further, introduction of small amounts of exogenous trans-sialidase
      into suspensions of nonpenetrating TS- parasites converted them to a highly
      invasive phenotype indistinguishable from that of the TS+ population. Rescue of
      the invasive phenotype was specific for the T. cruzi enzyme, for it didn't happen
      with bacterial and viral sialidases. The in vitro results were confirmed in the
      murine model of Chagas' disease, as TS- trypomastigotes were relatively avirulent
      while TS+ trypomastigotes were more virulent than unfractionated parasites.

PMID- 8751945
TI  - Murine granulated metrial gland cells are susceptible to Chlamydia psittaci
      infection in vivo.
AB  - Granulated metrial gland (GMG) cells are the most numerous lymphoid cells in the
      uteroplacental unit in rodent pregnancy. In an experimental murine model of
      abortion-causing infection, we have studied the responses of GMG cells to
      Chlamydia psittaci. Chlamydial inclusions have been found within GMG cells, both
      in apparently healthy cells and in cells with degenerative changes. Establishing
      the existence of GMG cells infected by C. psittaci opens a new and interesting
      chapter in the study of these cells.

PMID- 8751946
TI  - Transforming growth factor beta is protective in host resistance against Listeria
      monocytogenes infection in mice.
AB  - The role of transforming growth factor beta (TGF-beta) in host resistance against
      Listeria monocytogenes infection was studied with mice. The constitutive
      expression of TGF-beta 1 mRNA was observed in the spleens and livers of mice
      before and after infection. Injecting the mice with anti-TGF-beta 1 peptide serum
      resulted in diminished antilisterial resistance, whereas the administration of
      human platelet-derived TGF-beta 1 enhanced the resistance. Moreover, mice were
      protected against lethal infection when treated with TGF-beta 1. These results
      suggest the TGF-beta 1 might be involved in antilisterial resistance. On the
      other hand, injecting the mice with TGF-beta 1 resulted in a decrease in the
      titers of endogenous gamma interferon, tumor necrosis factor alpha, and
      interleukin-6, which are crucial in antilisterial resistance, in sera and in
      extracts of spleen and liver. Thus, a complicated mechanism might be involved in
      the role of TGF-beta 1 in host resistance against L. monocytogenes infection.

PMID- 8751947
TI  - Influence of Actinobacillus pleuropneumoniae and its metabolites on porcine
      alveolar epithelial cells.
AB  - The effect of Actinobacillus pleuropneumoniae and its metabolites on the
      viability of porcine alveolar epithelial cells was studied by using a neutral-red
      uptake test. Alveolar epithelial cells were obtained from 5-week-old colostrum
      deprived pigs. The purity of these cells as assessed by the modified Papanicolaou
      stain was 90 to 95%. Incubation of these cells with 10(6) CFU of a biotype 1
      serotype 1 strain resulted in death of the alveolar epithelial cells within 1.5
      h. A cytotoxic effect was also seen when alveolar epithelial cells were incubated
      with sterile culture supernatants of biotype 1 serotype 1, biotype 1 serotype 10,
      and biotype 2 serotype 2 strains or with ApxI, ApxII, or ApxIII produced by
      recombinant Escherichia coli. Incubation of alveolar epithelial cells with a
      knockout mutant of the biotype 1 serotype 1 parent strain which is unable to
      secrete Apx toxins or with its supernatant did not result in death of these
      cells. These results indicate that cytotoxicity is at least in part due to
      production of Apx toxins.

PMID- 8751948
TI  - Influence of anti-Actinobacillus actinomycetemcomitans Y4 (serotype b)
      lipopolysaccharide on severity of generalized early-onset periodontitis.
AB  - The objective of this study was to determine if a relationship exists between
      antibody reactive with the Actinobacillus actinomycetemcomitans serotype b
      lipopolysaccharide (LPS) and severity of periodontal disease in generalized early
      onset periodontitis (G-EOP). The concentration of antibody reactive with A.
      actinomycetemcomitans serotype b LPS was determined for 102 G-EOP subjects.
      Analysis of the relationship between antibody reactive with A.
      actinomycetemcomitans serotype b LPS and measures of periodontal attachment loss
      indicated that the patients with the highest concentrations of antibody reactive
      with A. actinomycetemcomitans serotype b LPS had significantly less attachment
      loss. These high-responder subjects also had anti-A. actinomycetemcomitans
      serotype b LPS with significantly higher relative avidity. The results suggest
      that antibody reactive with A. actinomycetemcomitans serotype b LPS is protective
      in G-EOP patients.

PMID- 8751949
TI  - Absolute identification of muramic acid, at trace levels, in human septic
      synovial fluids in vivo and absence in aseptic fluids.
AB  - This is the first report of a study employing the state-of-the-art technique of
      gas chromatography-tandem mass spectrometry for absolute identification of
      muramic acid (a marker for peptidoglycan) at trace levels in a human or animal
      body fluid or tissue. Daughter mass spectra of synovial fluid muramic acid peaks
      (> or = 30 ng/ml) were identical to those of pure muramic acid. Absolute chemical
      identification at this level represents a 1,000-fold increase in sensitivity over
      previous gas chromatography-mass spectrometry identifications. Muramic acid was
      positively identified in synovial fluids during infection and was eliminated over
      time but was absent from aseptic fluids.

PMID- 8751950
TI  - Role of gamma-delta T cells in murine Chlamydia trachomatis infection.
AB  - The role of gamma-delta T cells in host resistance to Chlamydia trachomatis was
      characterized by using a murine model of pneumonia caused by the mouse
      pneumonitis agent (MoPn), murine C. trachomatis. At days 3 and 7 after infection,
      gamma-delta T-cell-deficient knockout mice had significantly higher levels of
      MoPn in the lungs than did immunologically intact controls. At day 20,
      paradoxically, gamma-delta T-cell-deficient mice were more resistant to MoPn than
      were controls. This increased resistance was not due to an increased production
      of toxic cytokines or interleukin-10 in controls on that day. Gamma-delta T cells
      play a role in protection early in MoPn infection, but they may be deleterious
      later in infection, as has been observed in models of salmonella and trypanosome
      infection.

PMID- 8751951
TI  - Outer membrane protein B1, an iron-repressible protein conserved in the outer
      membrane of Moraxella (Branhamella) catarrhalis, binds human transferrin.
AB  - Moraxella (Branhamella) catarrhalis is a gram-negative human mucosal pathogen,
      which primarily causes otitis media in young children. However, this bacterium is
      also a common cause of lower respiratory tract infections in adults with
      underlying lung disease. Our previous data have shown that M. catarrhalis
      expresses iron-repressible outer membrane proteins in response to iron
      limitation. We have extended these observations to demonstrate that one of these
      proteins, termed outer membrane protein (OMP) B1, binds human transferrin. Using
      a newly developed monoclonal antibody to OMP B1, we determined that this protein
      is conserved in the iron-stressed outer membranes of all clinical isolates of M.
      catarrhalis tested to date. Furthermore, our data have confirmed that children
      infected with M. catarrhalis have immunoglobulin G antibodies to OMP B1 in their
      convalescent sera. These current data suggest that OMP B1 is immunogenic and
      expressed in vivo and may be involved in an iron uptake mechanism utilized by M.
      catarrhalis.

PMID- 8751952
TI  - Iron availability affects entry of Listeria monocytogenes into the enterocytelike
      cell line Caco-2.
AB  - The influence of iron on the entry of Listeria monocytogenes into Caco-2 cells
      was studied. Iron availability was found to modify the surface hydrophobicity and
      protein profile of L. monocytogenes, with the result that cell invasion strongly
      increased upon bacterial growth in iron-rich medium. The enhanced invasive
      capability of iron-overloaded L. monocytogenes cells correlates to the higher
      level expression of the inlAB virulence genes, which were positively iron
      regulated at the transcriptional level.

PMID- 8751953
TI  - Phospholipid metabolism induced by Clostridium perfringens alpha-toxin elicits a
      hot-cold type of hemolysis in rabbit erythrocytes.
AB  - GTP and AIF4- significantly stimulated the late phosphatidic acid (PA) formation
      induced by Clostridium perfringens alpha-toxin in rabbit erythrocyte lysates.
      Pertussis toxin blocked the PA production. AIF4- markedly enhanced
      phosphatidylethanol production induced by alpha-toxin in the presence of ethanol.
      GTP[gamma S] stimulated the PA formation and hemolysis induced by alpha-toxin,
      and GDP[beta S] inhibited them. An H-to-G mutation at position 126 (H126G)
      induced the PA formation and hemolysis in a Co2+ concentration-dependent manner.
      H148G induced neither the PA formation nor hemolysis. These results suggest that
      the toxin-induced hemolysis is due to activation of phospholipid metabolism
      systems through GTP-binding protein.

PMID- 8751954
TI  - Urease activity does not contribute dramatically to persistence of Mycobacterium
      bovis bacillus Calmette-Guerin.
AB  - Multiplication of BCGure-, an isogenic urease-negative mutant of Mycobacterium
      bovis BCG constructed by allelic exchange (J. M. Reyrat, F. X. Berthet, and B.
      Gicquel, Proc. Natl. Acad. Sci. USA 92:8768-8772, 1995), was examined in human
      macrophages and mice. Although ureolytic activity was not essential to BCGure
      growth, a slight decrease in the multiplication and persistence of the mutated
      strain compared with wild-type BCG was observed in lungs of infected mice.

PMID- 8751955
TI  - Apoptosis of lymphocytes in mice induced by infection with Rickettsia
      tsutsugamushi.
AB  - Histological examinations of mice infected with either a lethal (Karp) or a self
      limitating (Gilliam) strain of Rickettsia tsutsugamushi were performed. Tingible
      body macrophages in the spleen and necrotizing lymphadenitis in regional lymph
      nodes were prominent only in the former. Apoptotic legions in the lymphocytes of
      these organs were clearly demonstrated by histochemical and electron
      microscopical examinations.

PMID- 8751957
TI  - Treatment with the antigranulocyte monoclonal antibody RB6-8C5 impairs resistance
      of mice to gastrointestinal infection with Listeria monocytogenes.
AB  - Treatment with the antigranulocyte monoclonal antibody (MAb) RB6-8C5 increased
      the severity of infection in mice intragastrically inoculated with Listeria
      monocytogenes. Most MAb RB6-8C5-treated mice died when inoculated
      intragastrically with as few as 4 x 10(4) L. monocytogenes bacteria, whereas most
      control mice survived intragastric inoculation with 4 x 10(8) L. monocytogenes
      bacteria. The increased severity of infection in MAb RB6-8C5-treated mice
      appeared to result from listerial multiplication in the spleen and liver rather
      than from local proliferation in the intestinal tract or mesenteric lymph nodes.

PMID- 8751956
TI  - Immune response to Shigella sonnei in U.S. Marines.
AB  - Pre- and postdeployment serum samples obtained from U.S. marines in Operations
      Desert Shield and Desert Storm were tested for antibodies to Shigella sonnei.
      High predeployment levels of immunoglobulin A (IgA) and/or IgG antibodies to S.
      sonnei lipopolysaccharide antigen in serum and seroconversions were accompanied
      by higher IgA and/or IgG antibody response to Shigella invasion plasmids (Ipa).
      The results suggest exposure to S. sonnei in predeployment troops and frequent
      exposure to this bacterial agent during deployment.

PMID- 8751958
TI  - Xeroderma pigmentosum knockout mice: an immunologic tale.

PMID- 8751959
TI  - Analysis of desmosomal cadherin-adhesive function and stoichiometry of desmosomal
      cadherin-plakoglobin complexes.
AB  - Desmosomes are intercellular adhesive junctions that associate with the
      intermediate filament cytoskeleton. The two major classes of transmembrane
      desmosomal glycoproteins, desmogleins and desmocollins, are widely considered to
      function as adhesion molecules. This assumption is based in part on their
      homology to the cadherin family of calcium-dependent homophilic adhesion
      molecules. In addition, autoantibodies from pemphigus patients bind directly to
      desmoglein family members and are thought to cause epidermal blistering by
      inhibiting the function of these cadherins. To directly test the ability of the
      desmosomal cadherins to mediate adhesion, desmoglein-1 (Dsg1), desmocollin-2
      (Dsc2a) and plakoglobin were expressed in mouse L cell fibroblasts. Similar to
      catenin:classical cadherin complexes, plakoglobin:Dsc2a complexes exhibited an
      approximately 1:1 stoichiometry; however, plakoglobin:Dsg1 complexes exhibited a
      6:1 stoichiometry. When L cells expressing the desmosomal cadherins were tested
      for the ability to aggregate in suspension, L cells expressing E-cadherin
      exhibited extensive aggregation, but L cells expressing Dsg1 or Dsc2a did not
      aggregate. In addition, L cells co-expressing Dsg1, Dsc2a, and plakoglobin failed
      to aggregate. The cytoplasmic domain of E-cadherin is thought to play a central
      role in the adhesive function of E-cadherin by providing a link to the actin
      cytoskeleton. Therefore, two chimeric cadherins comprising the cytoplasmic domain
      of E-cadherin and the extracellular domain of either Dsg1 or Dsc2a were expressed
      in L cells. Both chimeras formed a complex with alpha- and beta-catenin.
      Nevertheless, neither of these chimeras supported aggregation of L cells when
      expressed individually or when co-expressed. These data suggest that the
      extracellular domains of the desmosomal cadherins exhibit functional properties
      distinct from those of the classical cadherins, such as E-cadherin.

PMID- 8751960
TI  - Evidence against a role for human T-cell lymphotrophic virus type I (HTLV-I) in
      the pathogenesis of American cutaneous T-cell lymphoma.
AB  - We used a standard polymerase chain reaction (PCR)/Southern blot assay
      (sensitivity > 10(-5)) to detect human T-cell lymphotrophic virus type I (HTLV-I)
      proviral pX, pol, and env genes in the lesional skin of 42 American patients with
      cutaneous T-cell lymphoma (CTCL). As in some prior reports using similar methods,
      a variable proportion of PCR tests were positive (seven of 42 for pX, three of 42
      for pol, and two of 37 for env), resulting in an overall positive test rate of 12
      of 121 (10%). To determine the significance of these positive test results, we
      performed several additional studies. D1S80 polymorphism analysis of CTCL cases
      and HTLV-I PCR analysis of non-CTCL dermatosis controls showed no evidence that
      positive PCR tests resulted from sample mislabeling, gross HTLV-I contamination,
      or human endogenous retroviruses. We then modified the standard PCR assay to
      incorporate ultraviolet (UV) light to destroy low-level PCR contamination. With
      this modified assay (sensitivity > 10(-5)), only three of 12 previously positive
      cases were still positive, suggesting that the earlier positives were due to
      trace contamination of PCR reagents or trace contamination of sample DNA. This
      interpretation was also supported by: (i) a match between pX and pol sequences
      cloned from one PCR-positive specimen and the MT4-positive control, (ii) our
      inability to confirm HTLV-I in any PCR-positive case using genomic dot blotting
      (sensitivity > 10(-2)), and (iii) negative PCR results when new samples from two
      of the remaining positive cases were analyzed. Finally, we used our modified UV/
      PCR/Southern blot assay to test an additional 28 cases of American CTCL for pX.
      All of them were negative. Although these studies of 70 cases of American CTCL do
      not exclude the possibility that another virus is involved in the pathogenesis of
      this disease, they provide strong evidence against a role for HTLV-I.
      Furthermore, they emphasize the need for special strategies to control for false
      positive PCR tests that can result from even trace levels of contamination with
      viral DNA. As a consequence, associations between diseases and viruses should be
      viewed skeptically if they are based primarily on conventional PCR data.

PMID- 8751961
TI  - Failure to detect human T-lymphotropic virus type-I proviral DNA in cell lines
      and tissues from patients with cutaneous T-cell lymphoma.
AB  - Previous molecular studies investigating the presence of HTLV-I proviral DNA in
      cell lines and tissue samples of patients with cutaneous T-cell lymphoma (CTCL)
      have reported a detection rate ranging from 0-92%. Despite the lack of
      epidemiologic data linking HTLV-I infection with CTCL, the molecular data still
      invite speculation regarding the precise role of HTLV-I in the pathogenesis of
      CTCL. To determine the detection rate of HTLV-I proviral DNA among CTCL patients
      referred to our medical center, we analyzed Epstein-Barr virus-transformed cell
      lines established from peripheral blood of seven CTCL patients and 43 tissue
      samples from 22 patients with different stages of disease. Genomic DNA was
      polymerase chain reaction-amplified with primers within the HTLV-I tax gene
      region. Amplification products were probed with nested oligonucleotide probes by
      Southern blot analysis. No HTLV-I proviral sequences were detected in the samples
      (0/50). Using HTLV-I/II pol primers, no HTLV-I pol gene sequences were detected.
      In tissues from one patient, HTLV-II pol and tax gene sequences were detected;
      however, HTLV-II proviral integration was not detected by Southern blot analysis
      of the genomic DNA. Our data suggest: (i) HTLV-I does not appear to be a primary
      etiologic agent in CTCL; and (ii) HTLV-II pol and tax gene sequences can be
      detected in a minority of CTCL patients, but this does not necessarily imply an
      etiologic role.

PMID- 8751962
TI  - Quantification of Pro alpha 1(I) collagen mRNA in skin biopsy specimens: levels
      of transcription in normal skin and in granuloma annulare.
AB  - The synthesis of type I collagen, the major component of the skin, is known to be
      modulated in aging and in various skin diseases and treatments. In vivo analysis
      of type I collagen expression, however, is difficult because of the low cell
      density of the dermis and the small amount of RNA obtainable from skin biopsy
      specimens. We present here a quantitative polymerase chain reaction method for
      the quantification of pro alpha 1(I) collagen mRNA in skin punch biopsy
      specimens. The targeted mRNA and a synthetic RNA as an internal standard were co
      amplified together with the same primers. Collagen synthesis was found to decline
      after birth, so that the amount of pro alpha 1(I) collagen mRNA in the skin of 5-
      to 58-y-old donors was 17-37% of that in fetal skin. Slot-blot hybridization also
      indicated that the amount of pro alpha 1(I) collagen mRNA was much lower in adult
      skin than in fetal skin. In samples from lesional skin of two granuloma annulare
      patients, the number of pro alpha 1(I) mRNA molecules was increased 4- or 5-fold
      compared with values from nonlesional skin of the same patients. The method
      presented is a highly sensitive polymerase chain reaction application, requiring
      only very small amounts of total RNA.

PMID- 8751963
TI  - Infrequent mutation of p16INK4 in sporadic melanoma.
AB  - Loss of heterozygosity of chromosome region 9p21 occurs commonly and early in
      sporadic melanoma, suggesting the involvement of a tumor suppressor gene at this
      locus in the pathogenesis of this neoplasm. Although germline mutations and
      deletions of the p16INK4 gene located at 9p21 have been reported in familial
      melanoma, the relative contributions of mutation and deletion in sporadic
      melanoma are at present unclear. In this study, we investigated 26 cases of
      sporadic cutaneous melanoma (14 of which demonstrated loss of heterozygosity at
      9p21) for mutations of p16INK4. One tumor with allelic loss of 9p contained a CC-
      >TT mutation at codons 57/58, altering an arginine to a stop codon, consistent
      with bi-allelic inactivation of p16INK4 in this case. No mutations were
      identified in any of the other melanomas, or in one benign intradermal nevus with
      atypical features and two Spitz nevi that also showed loss of heterozygosity of
      9p. The inactivation of both copies of p16INK4 in the one case of melanoma adds
      support to the theory that p16INK4 is important in the development of sporadic
      cutaneous melanoma, although allelic loss or other methods of inactivation of
      p16INK4 rather than point mutation appears to be numerically more important. The
      low frequency of mutation of p16INK4 in cases of sporadic melanoma with loss of
      heterozygosity of 9p is, however, also consistent with there being another tumor
      suppressor gene near this locus that is involved in some cases of sporadic
      melanoma.

PMID- 8751964
TI  - Imbalance in the antioxidant pool in melanoma cells and normal melanocytes from
      patients with melanoma.
AB  - In order to evaluate the free radical defense systems of melanocytes and their
      possible correlation with melanoma, we have studied in cultured normal human
      melanocytes (20), normal melanocytes from melanoma patients (15), and melanoma
      cells (40) the fatty acid pattern of membrane phospholipids as a target of
      peroxidative damage and the superoxide dismutase and catalase activities, vitamin
      E, and ubiquinone levels as intracellular antioxidants. Cells were cultured in
      the same medium and analyzed at III or IV passage. Compared to the values
      obtained in normal human melanocytes, melanoma cells showed on average: a) higher
      levels of polyunsaturated fatty acids, b) increased superoxide dismutase and
      decreased catalase activities, higher vitamin E, and lower ubiquinone levels.
      Among the normal melanocytes from melanoma patients studied, two groups were
      differentiated: a) cultures (7) with enzymatic and non-enzymatic antioxidants
      level similar to those of normal human melanocytes; b) cultures (8) with
      antioxidant patterns similar to those observed in melanoma cells. Polyunsaturated
      fatty acids were also increased in the latter group. The results indicate that in
      melanoma cells and in a percentage of normal melanocytes from melanoma patients,
      an imbalance in the antioxidant system can be detected that can lead to
      endogenous generation of reactive oxygen species and to cellular incapability of
      coping with exogenous peroxidative attacks. These alterations could be correlated
      with the malignant transformation of cells and with the progression of the
      disease.

PMID- 8751965
TI  - Nitric oxide is generated on the skin surface by reduction of sweat nitrate.
AB  - Nitric oxide (NO) is known to be synthesized by mammalian cells from L-arginine
      by a group of NO synthase enzymes. We now show that NO is generated from human
      skin and propose a different mechanism of production. Whereas enzymatic NO
      synthesis is inhibited by monomethyl L-arginine, this arginine analog, when
      infused into the brachial artery at concentrations sufficient to inhibit
      endothelial NO synthase activity, has little effect on hand skin NO production.
      Hand skin NO production is increased by topical acidification of the skin surface
      and greatly increased by the addition of nitrite solutions. We propose that NO
      generation from skin derives from sweat nitrite (the concentration of which was
      found to average 3.4 microM in six subjects) due to chemical reduction consequent
      to the acidic nature of sweat. Sweat contains nitrate in appreciable amounts, and
      skin commensal bacteria can synthesize nitrate reductase enzyme. Patients on long
      term tetracycline antibiotics showed significantly reduced skin NO synthesis,
      although topical antiseptic and antibiotics had little effect on NO generation in
      the short-term. We propose that NO generation from skin is dependent on bacterial
      nitrate reduction to nitrite and subsequent reduction by acidification. We
      speculate that this has a physiologic role in the inhibition of infection by
      pathogenic fungi and other susceptible microorganisms and may affect cutaneous T
      cell function, keratinocyte differentiation, and skin blood flow.

PMID- 8751966
TI  - Oleic acid and linoleic acid are the major determinants of changes in
      keratinocyte plasma membrane viscosity.
AB  - Keratinocytes were grown in medium with no essential fatty acids as well as in
      media with specially selected fatty acid augmentations. Gas chromatographic
      determinations of 21 fatty acids in the phospholipids were correlated with plasma
      membrane viscosity obtained by electron paramagnetic resonance studies (n = 24).
      Using standard procedures from multivariate analysis, we derived an expression
      that modeled the viscosity data as a function of four key fatty acid levels:
      [formula see text] where the fatty acids are given in mole percent of total
      lipids and are identified as two number sequences: number of carbons followed by
      number of double bonds. No other fatty acid made a significant contribution to
      the regression equation. The range of viscosity was very large, varying from 60
      to 120 cP over the sample population. The results are interpreted to indicate
      that polyunsaturated fatty acids are replaced with monounsaturated fatty acids by
      the keratinocytes and that dihomogamma-linolenic acid (20:3, n-6) plays an
      important role in membrane viscosity when essential fatty acids are available in
      the growth medium of these adult human cultured keratinocytes.

PMID- 8751967
TI  - Inhibitors of sphingolipid synthesis modulate interferon (IFN)-gamma-induced
      intercellular adhesion molecule (ICAM)-1 and human leukocyte antigen (HLA)-DR
      expression on cultured normal human keratinocytes: possible involvement of
      ceramide in biologic action of IFN-gamma.
AB  - To elucidate the participation of sphingosine and ceramide in the biologic action
      of cytokines on epidermal keratinocytes, we studied whether inhibitors of
      sphingolipid synthesis modulate interferon (IFN)-gamma-induced intercellular
      adhesion molecule (ICAM)-1 and human leukocyte antigen (HLA)-DR expression on
      cultured normal human keratinocytes. Pretreatment of keratinocytes with L
      cycloserine or fumonisin B1, but not 1-phenyl-2-decanoylamino-3-morpholino-1
      propanol (PDMP), significantly suppressed both ICAM-1 and HLA-DR expression
      induced by IFN-gamma. Because the synthesis of all kinds of sphingolipids is
      blocked by L-cycloserine and all except that of sphinganine by fumonisin B1,
      whereas PDMP inhibits the synthesis of glucosylceramide and glycosphingolipids,
      the result suggests the participation of ceramide and/or sphingosine in IFN-gamma
      induced ICAM-1 and HLA-DR expression. Exogenous C2-ceramide reversed the effects
      of L-cycloserine and fumonisin B1. On the other hand, sphingosine reversed the
      effect of L-cycloserine, but not of fumonisin B1. These results indicate that
      ceramide participates in this pathway, as fumonisin B1, but not L-cycloserine,
      inhibits the synthesis of ceramide from sphingosine. In addition, reverse
      transcriptase polymerase chain reaction showed that L-cycloserine reduced the
      mRNA for ICAM-1, HLA-DR alpha, and HLA-DR beta induced by IFN-gamma, and C2
      ceramide and sphingosine antagonized the effect of L-cycloserine. Furthermore,
      the degradation rate of fluorescent sphingomyelin into ceramide in keratinocytes
      was increased by IFN-gamma, suggesting that IFN-gamma activates sphingomyelin
      hydrolysis in keratinocytes. These observations suggest the possible role of
      ceramide in IFN-gamma-induced ICAM-1 and HLA-DR expression on keratinocytes.
      Ceramide may function as an endogenous modulator mediating the cytokine signals
      in keratinocytes.

PMID- 8751968
TI  - Enhanced inflammation and immunosuppression by ultraviolet radiation in xeroderma
      pigmentosum group A (XPA) model mice.
AB  - Xeroderma pigmentosum group A (XPA) gene-deficient mice were developed by gene
      targeting in mouse embryonic stem cells. To examine whether these XPA-model mice
      display photodermatologic abnormalities similar to those in human xeroderma
      pigmentosum, we investigated the effects of acute ultraviolet radiation on the
      homozygous (-/-) mice compared to the wild type (+/+) and heterozygous (+/-)
      mice. A single irradiation with ultraviolet B or topical psoralen plus
      ultraviolet A treatment induced stronger and longer lasting ear swelling in the (
      /-) mice than in the (+/+) and (+/-) mice. Histologic changes including epidermal
      necrosis, cell infiltration, and sunburn cell formation after ultraviolet B
      radiation were more prominent in the (-/-) model mice than in the control mice.
      The (-/-) model mice showed damage of ADPase(+)Langerhans cells at a lower
      ultraviolet B dose than did the control mice. Moreover, the reappearance of
      ADPase(+)Langerhans cells after ultraviolet B radiation was delayed in the (-/-)
      mice compared to the control mice. Although contact hypersensitivity was induced
      equally in all mice, ultraviolet B-induced local and systemic immunosuppression
      were greatly enhanced in the (-/-) model mice. The data suggest that the XPA gene
      deficient mice may be a useful model of human XPA, because the responses to UV
      radiation in the mice were very similar to those in the patients with XPA.
      Moreover, it is possible that enhanced ultraviolet immunosuppression is involved
      in the development of skin cancers in xeroderma pigmentosum.

PMID- 8751969
TI  - A simple method for diagnosing xeroderma pigmentosum variant.
AB  - Patients with xeroderma pigmentosum variant have been diagnosed based on a post
      replication repair assay using their cells together with their clinical
      manifestations. We present here an alternative simple method for the diagnosis of
      xeroderma pigmentosum variant that measures three cellular markers for DNA repair
      by autoradiography, unscheduled DNA synthesis, recovery of RNA synthesis, and
      recovery of replicative DNA synthesis after ultraviolet irradiation. Fibroblasts
      from a patient are plated on three coverslips parallel with normal cells
      (control). Unscheduled DNA synthesis, recovery of RNA synthesis, and recovery of
      replicative DNA synthesis after ultraviolet irradiation in the patient's cells
      are compared with those of adjacent normal cells by counting numbers of grains on
      nuclei for each coverslip. Of the hereditary photosensitive disorders including
      xeroderma pigmentosum, Cockayne syndrome, and newly established ultraviolet
      sensitive syndrome, only xeroderma pigmentosum variant cells exhibit normal
      unscheduled DNA synthesis, normal recovery of RNA synthesis, but reduced recovery
      of replicative DNA synthesis (approximately 50% of that of control cells). This
      reduction of DNA synthesis is enhanced in the presence of caffeine. Because each
      disorder yields a different combination of these three markers, this method also
      provides a systematic basis for the diagnosis of these diseases.

PMID- 8751970
TI  - Epidermal protein kinase C-beta 2 is highly sensitive to downregulation and is
      exclusively expressed in Langerhans cells: downregulation is associated with
      attenuated contact hypersensitivity.
AB  - Treatment of mice with multiple topical applications of 12-O-tetradecanoylphorbol
      13-acetate (TPA) or diacylglycerol resulted in a preferential decrease in
      epidermal protein kinase C-beta 2 (PKC-beta 2) compared with PKC-alpha as
      determined by western analysis. When PKC-alpha was decreased by 40%, PKC-beta 2
      could no longer be detected, suggesting that PKC-beta 2 is more sensitive to
      downregulation, and/or specific epidermal cell types that contain PKC-beta 2 are
      more sensitive to TPA/diacylglycerol. To address this issue, we isolated
      Langerhans cells (LCs) from epidermal cell suspensions with immunomagnetic beads
      and an antibody to the class II major histocompatibility complex. Northern blot
      analysis revealed a PKC-beta 2 signal in isolated LCs that was 40-fold greater
      than that observed in unfractionated epidermal cells, and no PKC-beta 2 signal
      was detected in epidermal cells depleted of LCs, indicating that PKC-beta 2 is
      expressed exclusively in LCs within the epidermis. Western blot analysis
      confirmed the presence of PKC-beta 2 in LCs. PKC-beta 2 was highly sensitive to
      downregulation, because a single application of TPA resulted in a 90% loss of PKC
      beta 2 within 6 h without a decrease in the number of LCs. To determine whether
      the decreased level of PKC-beta 2 within LCs was associated with an alteration in
      contact hypersensitivity, we treated mice with only a single application of TPA,
      and 6 hours later mice were sensitized with 2,4-dinitrofluorobenzene on the same
      dorsal area. Subsequent challenge revealed a 60% decrease in contact
      hypersensitivity in TPA-treated mice. These data indicate that (i) within the
      epidermis, PKC-beta 2 is highly sensitive to downregulation and is exclusively
      expressed in LCs, and (ii) the downregulation of PKC-beta 2 is associated with
      impaired LC function with respect to contact hypersensitivity.

PMID- 8751971
TI  - Interferon-gamma inducible protein (IP-10) expression is mediated by CD8+ T cells
      and is regulated by CD4+ T cells during the elicitation of contact
      hypersensitivity.
AB  - To investigate the potential roles of CD4+ and CD8+ T cells during contact
      hypersensitivity, we examined the T-cell-dependent expression of proinflammatory
      cytokine genes in the responses to dinitrofluorobenzene and oxazolone. Whole cell
      RNA was isolated from challenged ear tissue and analyzed for level of cytokine
      gene expression by Northern blot and densitometry analysis. Expression of
      interleukin 1 beta and the three chemokine genes (IP-10, JE, and KC) examined was
      dependent on the hapten dose used for sensitization and correlated with the
      immune response, i.e., ear swelling, elicited. Antibody-mediated depletion of
      CD8+ T cells before sensitization resulted in the absence of IP-10 expression
      following hapten challenge, indicating the ability of immune CD8+ T cells to
      mediate IP-10 expression. Depletion of CD4+ T cells resulted in higher levels of
      IP-10 and KC expression during elicitation of contact sensitivity, suggesting
      CD4+ T cells inhibit the expression of these proinflammatory genes. Depletion of
      CD4+ T cells resulted in contact hypersensitivity responses of higher magnitude
      and depletion of CD8+ T cells resulted in responses of lower magnitude. Transfer
      of CD8+ T-cell-depleted immune cells resulted in low, but detectable levels of IP
      10 expression, indicating the ability of some oxazolone-immune CD4+ T cells to
      mediate IP-10 expression. These results indicate the differential induction of
      proinflammatory cytokine gene expression during elicitation of contact
      hypersensitivity in which expression of IP-10 is primarily mediated by immune
      CD8+ T cells and inhibited by immune CD4+ T cells.

PMID- 8751972
TI  - Interleukin 4-induced proliferation in normal human keratinocytes is associated
      with c-myc gene expression and inhibited by genistein.
AB  - We studied the effect of IL-4 on the proliferation of cultured normal human
      keratinocytes. Keratinocyte proliferation was stimulated by IL-4 and inhibited by
      anti-IL-4 antibody in a concentration-dependent manner. Anti-IL-6 antibody did
      not inhibit normal human keratinocyte proliferation, suggesting that the IL-4
      could directly induce proliferation of these cells. IL-4 significantly induced
      cell cycle G0/G1 to S phase progression. The keratinocyte proliferation by IL-4
      was mediated through one of the growth control genes, c-myc protooncogene. The
      expression of c-myc mRNA was significantly increased after IL-4 treatment of the
      keratinocytes, suggesting that c-myc plays a key role in the control of
      proliferation. The signal transduction pathways induced by IL-4 in the
      keratinocytes were studied with inhibitors of signal transduction. Genistein, a
      tyrosine kinase inhibitor, suppressed the level of the induced c-myc mRNA
      expression, but H7, a serine/threonine kinase inhibitor, and okadaic acid, a
      protein phosphatase 1 and 2A inhibitor, did not block the induced c-myc gene
      expression. Taken together, these results suggest that IL-4 stimulates the
      proliferation of keratinocytes in vitro by promoting a transition from G0/G1 to S
      phase of the cell cycle. Induction of c-myc after IL-4 treatment could indicate
      an important role for c-myc in the proliferation of keratinocytes. Our
      observations also suggest that tyrosine kinases may be involved in IL-4-induced
      proliferation.

PMID- 8751973
TI  - HLA-DR5 and DQB1*03 class II alleles are associated with cutaneous T-cell
      lymphoma.
AB  - Cutaneous T-cell lymphoma (CTCL) may present with eczematous lesions, mycosis
      fungoides (MF), or as exfoliative erythroderma with circulating atypical cells,
      Sezary syndrome (SS). The "malignant" T cells are epidermotropic and clonal, but
      whether they respond to antigen stimulation is unknown. Because CD4+ lymphocytes
      recognize antigen presented by histocompatibility locus antigen (HLA) class II
      molecules, and HLA association have been found in autoimmune skin diseases, we
      determined by allele-specific oligonucleotide typing whether HLA-DR or DQ alleles
      were associated with CTCL and its two variants MF (n = 47) and SS (n = 23).
      Phenotypic frequencies were compared by chi-square and Fisher exact test, and p
      values were corrected independently for either 12 DR or 15 DQ alleles. HLA-DR5,
      previously associated with MF, was significantly increased in all 70 CTCL
      patients (31.5%) versus controls (11%) (uncorrected p value [Pnc] = 0.000038,
      odds ratio [OR] = 3.9, 1.9 < OR < 8.1), in MF patients (34%) (Pnc = 0.000047, OR
      = 3.62, 1.9 < OR < 10), and in SS patients (26%) (Pnc = 0.03, OR = 3, 0.9 < OR <
      9.3). HLA-DQB1*03 alleles (0301, 0302, and 0303) were increased in 72% of all
      CTCL patients versus 49% of controls (corrected p value [Pc] = 0.014, OR = 2.7,
      1.4 < OR < 5.1), in SS (82%) (Pc = 0.05, OR = 4.7, 1.4 < OR < 5), and in MF (67%)
      (Pnc = 0.024, OR = 2.15, 1 < OR < 4.5). DQB1*0502 was strongly increased in SS
      patients (Pc = 0.045, OR = 7.75, 1.25 < OR < 48). Although HLA-DQB1*0603 and HLA
      DR6 (1301, 1302, and 1402) were decreased in all groups, the decreases were not
      statistically significant. These data suggest that certain HLA-DRB and DQB1
      alleles, also associated with other T-cell-mediated skin diseases, may
      participate in the pathogenesis of or susceptibility to CTCL.

PMID- 8751974
TI  - Apoptosis is the predominant form of epithelial target cell injury in acute
      experimental graft-versus-host disease.
AB  - Cutaneous and mucosal epithelial cells are primary targets of injury in acute
      graft-versus-host disease (GVHD), the principal complication of allogeneic bone
      marrow transplantation. Recent experimental data in skin suggest that early
      lesion may precede morphologic evidence of direct infiltration by effector cells.
      The purpose of this study was to further elucidate the mechanism and kinetics of
      epithelial injury in acute GVHD produced in mouse strains (B10.BR/CBA) receiving
      bone marrow transplants across minor histocompatibility loci. Skin and tongue
      mucosa of hosts receiving CD8 T-cell-enriched, whole T-cell-enriched, or T-cell
      depleted bone marrow transplants were sequentially harvested and studied
      histologically and by the terminal uridine deoxynucleotidyl transferase end
      ligation technique to detect apoptotic cells. Apoptosis involving putative stem
      cells is the predominant form of cellular injury in acute experimental GVHD.
      Although apoptosis correlated with the onset of lymphocyte infiltration
      relatively late in CD8-mediated disease, apoptosis was bimodal in whole T-cell
      mediated disease, with an early peak that preceded histologic evidence of
      lymphocyte infiltration. These findings establish a central role for apoptosis in
      epithelial cell injury in acute GVHD and indicate that T-cell composition of the
      donor marrow inoculum may influence the pattern and kinetics of epithelial
      damage.

PMID- 8751975
TI  - Defective integrin alpha 6 beta 4 expression in the skin of patients with
      junctional epidermolysis bullosa and pyloric atresia.
AB  - Junctional epidermolysis bullosa (JEB) is a heterogeneous group of rare inherited
      skin disorders in which defects in cell adhesion components cause incomplete
      formation of hemidesmosomes. We have immunohistochemically examined the skin from
      ten JEB patients (JEB gravis, n = 4; JEB mitis, n = 3; JEB plus pyloric atresia
      [JEB/PA], n = 3) using monoclonal antibodies specific for the integrin adhesion
      receptors alpha 3 beta 1 and alpha 6 beta 4, and for the alpha 3, beta 3, and
      gamma 2 subunits of the basement membrane ligand, laminin 5. Consistent with our
      previous reports, only the JEB gravis patients without associated pyloric atresia
      expressed reduced or absent epitopes for laminin-5 subunits in their epidermal
      basement membrane. In contrast, all three JEB/PA cases showed abnormalities in
      integrin alpha 6 beta 4, but not in laminin 5, expression in their basal
      epidermal cells. Integrin beta 4 subunit was undetectable in the biopsied
      epidermis of these JEB/PA individuals using five different monoclonal antibodies
      that recognize both intra- and extracellular epitopes. The absence of the beta 4
      subunit in the epidermis of JEB/PA specimens was confirmed by Western blot
      analysis of tissue extracts. Epidermal expression of the integrin alpha 6 subunit
      was variable in the JEB/PA patients. Abnormal integrin alpha 6 beta 4 expression
      may define the subset of JEB cases with pyloric atresia. These results strongly
      implicate a functional role for alpha 6 beta 4 in the formation of complete
      hemidesmosomes and in stable adhesion of basal keratinocytes to the basement
      membrane in vivo.

PMID- 8751976
TI  - The immune response to class I-associated tumor-specific cutaneous T-cell
      lymphoma antigens.
AB  - In order to determine whether the neoplastic T cells from patients with cutaneous
      T-cell lymphoma express tumor-specific antigens that can serve as the targets of
      an immune response, we took advantage of family-specific monoclonal antibodies,
      magnetic bead technology, and recombinant cytokines, which provided the
      previously precluded ability to isolate and expand populations of purified tumor
      and autologous CD8 cytotoxic T cells. Four patients with advanced cutaneous T
      cell lymphoma had CD8 cells that specifically killed autologous tumor in a class
      I limited fashion. Tumor cell cytolysis could be specifically enhanced by pre
      culture with autologous gamma-irradiated tumor. The cytolytic T cells produced
      tumor necrosis factor-alpha in response to stimulation with autologous tumor. The
      presence of tumor-specific cytotoxic T cells recognizing distinctive class I
      associated molecules on cutaneous T-cell lymphoma tumor cells suggests that
      infiltration of early lesions by CD8 cells reflects host immunity to the
      neoplasm. These studies provide the foundation for the development of tumor
      vaccines through the use of cytotoxic T cells to isolate and characterize tumor
      associated cutaneous T-cell lymphoma peptides.

PMID- 8751977
TI  - Photosensitization of uroporphyrin augments the ultraviolet A-induced synthesis
      of matrix metalloproteinases in human dermal fibroblasts.
AB  - Porphyria cutanea tarda is characterized by severe connective tissue damage in
      sun-exposed skin. The regulated synthesis and degradation of the extracellular
      matrix by various matrix metalloproteinases (MMPs) determine its amount and
      composition within the skin. In this study, we therefore asked whether long-wave
      ultraviolet irradiation (340-450 nm) in conjunction with uroporphyrin I could
      modulate the synthesis of MMPs with substrate specificities for dermal (collagens
      I, III, V; proteoglycans) and basement membrane components (collagens IV, VII;
      fibronectin; laminin) and whether synthesis of the counteracting tissue inhibitor
      of metalloproteinases is also affected. After irradiation of uroporphyrin
      pretreated fibroblasts, specific mRNAs of MMP-1 and MMP-3 increased concomitantly
      up to 2.7-fold compared with ultraviolet-irradiated cells and up to 10-fold
      compared with mock-irradiated or uroporphyrin I-treated controls. In contrast,
      mRNA levels of tissue inhibitor of metalloproteinases remained unaltered. Similar
      results were obtained by immunoprecipitation. Gelatin and casein zymography
      revealed increased proteolytic activity of MMP-2 and MMP-3 in blister fluids of
      patients with porphyria cutanea tarda, indicating that similar events may occur
      in vivo. Using deuterium oxide as enhancer and sodium azide as quencher of
      singlet oxygen, we could increase or reduce MMP synthesis, suggesting that
      singlet oxygen is the major intermediate in the upregulation of MMPs after
      irradiation of uroporphyrin-pretreated fibroblasts. Taken together, our results
      show that ultraviolet irradiation alone, and to a greater extent in conjunction
      with uroporphyrin I, results in an unbalanced synthesis of MMPs that may
      contribute to the destruction of the dermis and basement membrane, leading to
      blistering and accelerated photoaging in porphyria cutanea tarda patients.

PMID- 8751978
TI  - Stimulation of fibroblast cell growth, matrix production, and granulation tissue
      formation by connective tissue growth factor.
AB  - Connective tissue growth factor (CTGF) is a 36-to 38-kDa peptide that is
      selectively induced by transforming growth factor-beta (TGF-beta) in fibroblastic
      cell types. We compared the biologic activities of CTGF with TGF-beta on
      fibroblasts in culture and in animal models of fibroplasia. CTGF was active as a
      mitogen in monolayer cultures of normal rat kidney fibroblasts. CTGF did not
      stimulate anchorage-independent growth of NRK fibroblasts, however, or inhibit
      the growth of mink lung epithelial cells, distinguishing CTGF's growth-regulatory
      activities from those of TGF-beta. In NRK fibroblasts, both TGF-beta and CTGF
      significantly increased the transcripts encoding alpha 1 type I collagen, alpha 5
      integrin, and fibronectin. Stimulation of type I collagen and fibronectin protein
      synthesis by TGF-beta and CTGF was confirmed by pulse labeling of cells with
      [35S]methionine. Subcutaneous injection of TGF-beta and CTGF into neonatal NIH
      Swiss mice resulted in a large stimulation of granulation tissue and fibrosis at
      the site of injection. In situ hybridization studies revealed that TGF-beta
      injection induced high levels of CTGF mRNA in the dermal fibroblasts at the
      injection site, demonstrating that TGF-beta can induce the expression of CTGF in
      connective tissue cells in vivo. No CTGF transcripts were detected in the
      epidermal cells in either control or TGF-beta-injected skin or in fibroblasts in
      control (saline-injected) skin. These results demonstrate that, like TGF-beta,
      CTGF can induce connective tissue cell proliferation and extracellular matrix
      synthesis.

PMID- 8751979
TI  - Activation of keratinocyte nicotinic cholinergic receptors stimulates calcium
      influx and enhances cell differentiation.
AB  - Human epidermal keratinocytes synthesize, secrete, and degrade acetylcholine and
      use their cell-surface nicotinic and muscarinic cholinergic receptors to mediate
      the autocrine and paracrine effects of acetyl-choline. Because acetylcholine
      modulates transmembrane Ca2+ transport and intracellular metabolism in several
      types of cells, we hypothesized that cholinergic agents might have similar
      effects on keratinocytes. Nicotine increased in a concentration-dependent manner
      the amount of 45Ca2+ taken up by keratinocytes isolated from human neonatal fore
      skins. This effect was abolished in the presence of the specific nicotinic
      antagonist mecamylamine, indicating that it was mediated by keratinocyte
      nicotinic acetylcholine receptor(s). The sequences encoding the alpha 5 and alpha
      7 nicotinic receptor subunits were amplified from cDNA isolated from cultured
      keratinocytes. These subunits, as well as the alpha 3, beta 2, and beta 4
      subunits previously found in keratinocytes, can be components of Ca(2+)-permeable
      nicotinic receptor channels. To learn how activation of keratinocyte nicotinic
      receptors affected the rate of cell differentiation, we measured the nicotinic
      cholinergic effects on the expression of differentiation markers by cultured
      keratinocytes. Long-term incubations with micromolar concentrations of nicotine
      markedly increased the number of cells forming cornified envelopes and the number
      of cells staining with antibodies to suprabasal keratin 10, transglutaminase type
      I, involucrin, and filaggrin. The increased production of these differentiation
      associated proteins was verified by Western blotting. Because nicotinic
      cholinergic stimulation causes transmembrane Ca2+ transport into keratinocytes,
      and because changes in concentrations of intracellular Ca2+ are known to alter
      various keratinocyte functions, including differentiation, the subcellular
      mechanisms mediating the autocrine and paracrine actions of epidermal
      acetylcholine on keratinocytes may involve Ca2+ as a second messenger.

PMID- 8751980
TI  - High-dose ultraviolet A1 (UVA1), but not UVA/UVB therapy, decreases IgE-binding
      cells in lesional skin of patients with atopic eczema.
AB  - In order to further elucidate the mechanisms by which high-dose ultraviolet A1
      (UVA1) therapy leads to improvement in patients with atopic eczema, we assessed
      skin sections from patients before and after high-dose UVA1 therapy (n = 5) or
      conventional UVA/UVB therapy (n = 4) for changes in Langerhans cells and mast
      cells expressing the high-affinity IgE receptor Fc epsilon RI and in surface
      bound IgE by histochemical and immunohistochemical techniques. The two treatment
      groups exhibited different patterns of changes in the number of Fc epsilon RI+,
      CD1a+, and mast cells within the dermis: The density of both Langerhans cells and
      mast cells was decreased after high-dose UVA1 therapy, but not after UVA/UVB
      therapy. High-dose UVA1 and UVA/UVB therapy significantly increased the number of
      CD1a+ cells within the epidermis, but only high-dose UVA1 reduced the relative
      number of IgE+ intraepidermal Langerhans cells typically found in atopic eczema.
      Reduction of numbers of dermal Langerhans cells and mast cells, as well as
      relative numbers of intraepidermal IgE+ Langerhans cells, was closely linked to
      significant clinical improvement by high-dose UVA1, but not UVA/UVB therapy.
      These studies support the notion that IgE-binding cutaneous cells are involved in
      the pathogenesis of atopic eczema. We propose that UVA1 radiation exerts its
      effects in atopic eczema, at least in part, by inhibiting Langerhans cell
      migration out of the epidermis and, in particular, by reducing the number of IgE
      bearing Langerhans cells and mast cells in the dermis.

PMID- 8751981
TI  - Rapid normalization of epidermal integrin expression after allografting of human
      keratinocytes.
AB  - Allogeneic keratinocyte grafts have beneficial effects on skin wounds, but the
      underlying interactions between graft and woundbed remain to be explored in
      detail. The epidermal integrins play a pivotal role in mediating cell-to-cell and
      cell-to-matrix interactions. In unwounded epidermis, alpha 2 beta 1-, alpha 3
      beta 1-, alpha 6 beta 4-, alpha 5 beta 1-, and alpha v beta 5-integrins are
      confined to basal cells. During healing of incisional wounds, these integrins are
      also expressed in suprabasal cells, where they remain detectable even after
      epidermal integrity is fully reestablished. We examined the integrin subunits
      alpha 2, alpha 3, alpha 6, alpha 5, and alpha v in partial thickness burn wounds
      grafted with allogeneic keratinocytes and asked whether the effect of allogeneic
      keratinocyte grafts, i.e., fast reepithelialization, is reflected by an
      accelerated reversion to a normal integrin pattern. Biopsies were taken after
      wound debridement before grafting and 10 d after transplantation. After 10 d, a
      stratified epidermis had developed in all cases and integrins were mainly
      restricted to the basal cell layer of the neo-epidermis. alpha 2-, alpha 3-,
      alpha 6-, and alpha v-subunits were present at basal and/or lateral cell borders,
      duplicating the integrin pattern in normal epidermis. The findings indicate that
      grafting accelerates the shift of the epidermis from an inflammatory to a
      regenerative state, as reflected by the reversion of the integrin pattern from a
      "spread-and-migrate" to the "steady-state" phenotype.

PMID- 8751982
TI  - A limited role for retinoic acid and retinoic acid receptors RAR alpha and RAR
      beta in regulating keratin 19 expression and keratinization in oral and epidermal
      keratinocytes.
AB  - Different types of stratified squamous epithelia-for example, the
      "orthokeratinized" epidermis, the "parakeratinized" gingiva, and the
      "nonkeratinized" oral lining mucosal epithelia-are formed by intrinsically
      distinct keratinocyte subtypes. These subtypes exhibit characteristic patterns of
      keratin protein expression in vivo and in culture. Keratin 19 is an informative
      subtype-specific marker because the basal cells of only nonkeratinizing epithelia
      express K19 in vivo and in culture. Epidermal keratinocytes normally do not
      express K19, but can be induced to do so in culture by retinoic acid (RA).
      Keratinocyte subtypes express the retinoic acid receptor (RAR) beta at levels
      roughly correlated with their level of K19 expression in culture and their
      potential for forming a nonkeratinized epithelium in vivo. We tested the
      hypothesis that the level of RAR beta expressed by a keratinocyte determines its
      K19 expression and its form of suprabasal differentiation. Normal human epidermal
      and gingival keratinocytes stably overexpressing either RAR beta or RAR alpha
      were generated by defective retroviral transduction. Overexpression of either
      receptor enhanced the RA inducibility of K19 in conventional culture, in that the
      proportion of the transductants becoming K19+ in response to RA was markedly
      increased compared with controls. The pattern of differentiation of the
      epithelium formed in organotypic culture, assessed by basal K19 and suprabasal
      K1, K4, and filaggrin expression, however, was unaltered by RAR overexpression.
      Thus, the susceptibility of keratinocytes to regulation of K19 expression by
      retinoids is conditional, and levels of neither RAR beta nor RAR alpha are
      limiting to the intrinsic mechanism that specifies alternate differentiation
      pathways for stratified squamous epithelia.

PMID- 8751984
TI  - Increased expression of the 72-kDa heat shock protein and reduced sunburn cell
      formation in human skin after local hyperthermia.

PMID- 8751983
TI  - A novel H1 mutation in the keratin 1 chain in epidermolytic hyperkeratosis.
AB  - We report a novel mutation in a case of epidermolytic hyperkeratosis that results
      in a proline for arginine substitution in the penultimate residue position of the
      H1 subdomain of the keratin 1 chain, which is near the beginning of the rod
      domain. This causes a severe clinical disease classified as PS-2. Therefore, the
      H1 subdomain is probably equally important for the maintenance of keratin
      intermediate filament integrity as the rod domain. Since earlier concepts had
      implied that mutations in the H1 subdomain produce milder disease, this case
      suggests that attempts to correlate mutations with disease presentation remain
      problematic.

PMID- 8751985
TI  - No correlation between cytomegalovirus and alopecia areata.

PMID- 8751986
TI  - An evaluation of possible mechanisms underlying amiodarone-induced pulmonary
      toxicity.
AB  - The effectiveness of amiodarone in the treatment of cardiac arrhythmias is
      limited due to the development of pulmonary toxicity. Although the biochemical
      and morphologic characteristics associated with amiodarone-induced pulmonary
      toxicity (AIPT) are well-defined, the mechanisms underlying this disorder remain
      unknown. This review focuses on proposed mechanisms of AIPT, in particular (i)
      direct cellular damage; (ii) the role of phospholipidosis; (iii) the correlation
      between drug burden and toxicity; (iv) the role of the immune system; (v) the
      generation of oxidants; (vi) changes in membrane properties; and (vii)
      miscellaneous biochemical considerations. Additional discussion of the role of
      amiodarone's primary metabolite, desethylamiodarone, in AIPT and the involvement
      of preexisting lung dysfunction in the susceptibility to AIPT is included. With a
      clearer understanding of the possible contributions of these mechanisms to AIPT,
      it may be possible to develop strategies to alleviate toxicity and prolong the
      usefulness of amiodarone in the treatment of cardiac arrhythmias.

PMID- 8751987
TI  - Molecular recognition in vitamin D-binding protein.
AB  - Vitamin D-binding protein (DBP) or group-specific component (Gc) is a relatively
      abundant serum protein with multiple functions, the majority of which are
      initiated by the highly specific recognition and binding of a ligand by this
      protein. During the past decade and a half, several structure-functional studies
      have been carried out to shed light on the physiological significance of the
      multiple functions of DBP. Results of these studies are discussed.

PMID- 8751988
TI  - Adhesive interactions in the hematopoietic system: regulation by cytokines.

PMID- 8751989
TI  - Catabolic hormones and growth hormone resistance in acquired immunodeficiency
      syndrome and other catabolic states.

PMID- 8751990
TI  - Effect of surgically induced endometriosis on pregnancy and effect of pregnancy
      and lactation on endometriosis in mice.
AB  - Endometriosis, a disease of women and nonhuman primates in which endometrial
      tissue grows outside the uterus, can be mimicked surgically in rats and mice. The
      disease is related to infertility in women, and surgical induction of
      endometriotic lesions reduces fertility in rats according to some studies.
      Conversely, pregnancy appears to have a beneficial effect on endometriosis in
      women and some rat studies. Our objective was to evaluate a new mouse model of
      surgically induced endometriosis with respect to the effects of pregnancy on
      endometriosis and the effects of endometriosis on pregnancy. Female B6C3F1 mice
      were divided into four groups. Those in Group A and B underwent induction surgery
      for endometriosis and hemi-ovariectomy, those in Group C underwent sham surgery
      and hemi-ovariectomy, and animals in Group D received no surgery at all. Three
      weeks later, Group A, C, and D were bred. Eighteen days later one half of the
      dams in Groups A, B, and C only were sacrificed, and evaluations included
      endometriotic lesion diameter, number of pups, fetal weight, and various organ
      weights. The remaining dams delivered, and, 18 days after parturition, dams and
      pups were sacrificed. Evaluations included gestation length and those listed
      above. Endometriotic lesion diameter was significantly reduced in pregnant
      animals when compared with nonpregnant controls, but the reduction was not a full
      regression. Lactation returned the mean lesion diameter to pre-pregnancy
      dimensions. When effects of endometriosis on pregnancy were evaluated, no effects
      on the litter size, pup weight, or gestation length were found, but trends toward
      increased resorptions and malformations were evident. Thus, in the mouse model of
      induced endometriosis, pregnancy produced a significant reduction in
      endometriotic lesion diameter while fertility was largely unaffected by the
      surgically induced endometriosis. The mouse model of endometriosis thus appears
      more resistant than the rat model to effects of endometriosis on fertility.

PMID- 8751991
TI  - Identification of formaldehyde as the metabolite responsible for the mutagenicity
      of methyl tertiary-butyl ether in the activated mouse lymphoma assay.
AB  - Methyl tertiary-butyl ether (MTBE), which is added to gasoline as an octane
      enhancer and to reduce automotive emissions, has been evaluated in numerous
      toxicological tests, including those for genotoxicity. MTBE did not show any
      mutagenic potential in the Ames bacterial assay or any clastogenicity in
      cytogenetic tests. However, it has been shown to be mutagenic in an in vitro gene
      mutation assay using mouse lymphoma cells when tested in the presence, but not in
      the absence, of a rat liver-derived metabolic activation system (S-9). In the
      present study, MTBE was tested to determine if formaldehyde, in the presence of
      the S-9, was responsible for the observed mutagenicity. A modification of the
      mouse lymphoma assay was employed which permits determination of whether a
      suspect material is mutagenic because it contains or is metabolized to
      formaldehyde. In the modified assay, the enzyme formaldehyde dehydrogenase (FDH)
      and its co-factor, NAD+ are added in large excess during the exposure period so
      that any formaldehyde produced in the system is rapidly converted to formic acid
      which is not genotoxic. An MTBE dose-responsive increase in the frequency of
      mutants and in cytotoxicity occurred without FDH present, and this effect was
      greatly reduced in the presence of FDH NAD+. The findings clearly demonstrate
      that formaldehyde derived from MTBE is responsible for mutagenicity of MTBE in
      the activated mouse lymphoma assay. Furthermore, the results suggest that the
      lack of mutagenicity/clastogenicity seen with MTBE in other in vitro assays might
      have resulted from inadequacies in the test systems employed for those assays.

PMID- 8751992
TI  - Preweaning diet programs postweaning plasma thyroxine concentrations in baboons.
AB  - We tested the hypothesis that breast- and formula-feeding of infant baboons
      affect postweaning plasma thyroid hormone concentrations and that differences in
      thyroid hormone concentrations are associated with long-term effects of infant
      diet on lipoprotein concentrations and cholesterol metabolism. Newborn baboons
      were breast-fed (n = 12) or fed formulas with a high polyunsaturated/saturated
      (P/S) fat ratio (n = 11) or with a low P/S ratio (n = 12) similar to baboon
      breast milk. Baboons were weaned at 14 weeks of age to a high cholesterol,
      saturated fat diet. Plasma thyroid hormone concentrations were measured in this
      group of baboons until about 223 weeks of age. Thyroid hormones were also
      measured at 400 weeks in a second group of adult baboons (n = 80) that as infants
      were either breast-fed or fed formulas with varying levels of cholesterol.
      Baboons breast-fed as infants averaged 11% higher (P < 0.03) thyroxine (T4)
      concentrations from 34 to 400 weeks of age compared with those fed formulas. From
      70 to 400 weeks of age breast-fed baboons had 10% lower T3/T4 ratios (P < 0.03).
      Breast- versus formula-feeding did not affect postweaning T3 and fT3
      concentrations. Postweaning thyroid hormone concentrations were not significantly
      affected by the P/S ratio or the cholesterol level of the infant formulas. The
      rank correlation of the means of the sire progeny groups for T4 and HDL-C
      concentrations was statistically significant (rn = -0.83; P < 0.05). Partial
      correlations of T4 concentrations with body weight, feed intake, or measures of
      cholesterol metabolism were not significant. T4 concentrations were significantly
      correlated with T3 concentrations (r = 0.42; P < 0.02), and T3 concentrations
      were correlated with bile acid synthesis rate (r = 0.47; P < 0.01), acyl-CoA
      cholesterol acyltransferase (r = 0.66; P < 0.001), and plasma HDL1-C levels (r = 
      0.49; P < 0.007). These effects suggest that altered thyroid hormone homeostasis
      may partially mediate the long-term differences in cholesterol metabolism caused
      by breast-versus formula-feeding.

PMID- 8751993
TI  - Ethanol-induced changes in insulin-like growth factors and IGF gene expression in
      the fetal brain.
AB  - Brain growth retardation is a major feature of the fetal alcohol syndrome (FAS).
      Insulin-like growth factors (IGF-I and IGF-II) have been shown to exert
      significant metabolic and growth-promoting effects. Previously, we showed that
      circulating levels of IGF-I as well as hepatic gene expression of both IGFs were
      decreased in newborn offspring of rats fed ethanol during pregnancy. This study
      investigated the effects of maternal ethanol ingestion on fetal rat brain growth
      and on levels of IGF-I and IGF-II, as well as their mRNAs, in fetal brain. IGF
      binding protein (IGFBP) levels also were determined. Rats were fed 5% w/v ethanol
      in a liquid diet during gestation (EF group). Weight-matched animals were pair
      fed equicaloric control diet (PF group) or were fed ad libitum (AF group). The
      mean fetal brain weight of EF offspring was 13% and 16% lower (P < 0.01) than
      that of PF and AF offspring, respectively. Body weight of EF pups was decreased
      to a greater extent, resulting in higher brain to body weight ratios in EF pups
      than in either control group (P < 0.05). IGF-I levels in EF pups decreased by 33%
      and 41% compared with the corresponding PF and AF values (P < 0.01). IGF-I mRNA
      levels decreased by 27% and 40% compared with PF and AF values, respectively. A
      positive correlation was observed between brain IGF-I level and brain weight (r =
      0.561, P < 0.01). IGF-II levels were not affected despite a 50% decrease in IGF
      II expression. In PF animals, the fetal brain IGF-I and IGF-II mRNA levels were
      reduced by 28% and 21%, apparently in response to undernutrition. IGF-binding
      proteins levels were low in the EF group but not statistically significant
      compared with control values. The diminished fetal brain concentration of IGF-I
      and decreased gene expression of IGFs may play a role in brain growth retardation
      associated with FAS.

PMID- 8751994
TI  - 5-hydroxytryptaminergic receptor-mediated regulation of growth hormone secretion
      in Holstein steers occurs via alpha 2-adrenergic-dependent and -independent
      mechanisms.
AB  - In vitro and in vivo experiments were used to determine the relationship between
      5-hydroxytryptaminergic and alpha 2-adrenergic receptors in regulation of growth
      hormone secretion in cattle. Activation of 5-hydroxytryptaminergic receptors (10(
      8), 10(-6), 10(-4) M quipazine) or alpha 2-adrenergic receptors (10(-8), 10(-6),
      10(-4) M clonidine) had no effect on secretion of growth hormone from perifused
      anterior pituitary cells. In vivo, quipazine (0.2 mg/kg body wt, i.v.) and
      clonidine (8 micrograms/kg body wt, i.v.), when injected separately, each
      maximized secretion of growth hormone in Holstein steers. However, concurrent
      administration of quipazine and clonidine at these doses additively increased
      secretion of growth hormone (mean areas under curves = 439, 914, 1425, and 2359
      +/- a pooled SEM of 246 ng.ml-1.min for vehicle, clonidine, quipazine, and
      quipazine plus clonidine treatments, respectively). Blockade of 5
      hydroxytryptaminergic receptors with cyproheptadine (0.2 or 1.0 mg/kg body wt,
      s.c., 0740 hr) decreased basal concentrations of growth hormone but had no effect
      on the ability of clonidine (8 micrograms/kg body wt, i.v., 0840 hr) to increase
      secretion of growth hormone (mean areas under curves = 591, 1218, 363, 1087, and
      1002 +/- a pooled SEM of 177 ng.ml-1.min for vehicle-vehicle, vehicle-clonidine,
      0.2 mg cyproheptadine-vehicle, 0.2 mg cyproheptadine-clonidine and 1.0 mg
      cyproheptadine-clonidine treatments, respectively). Blockade of alpha 2
      adrenergic receptors with either yohimbine (5 mg/kg body wt, s.c., 0740 hr) or
      idazoxan (20 mg/kg body wt, s.c., 0740 hr) suppressed both basal and 5
      hydroxytryptaminergic receptor-stimulated (0.2 mg quipazine/kg body wt, i.v.,
      0840 hr) secretion of growth hormone (mean areas under curves = 568, 1252, 410,
      and 558 +/- a pooled SEM of 108 ng.ml-1.min for vehicle-vehicle, vehicle
      quipazine, yohimbine-vehicle, and yohimbine-quipazine treatments, respectively,
      and means of 553, 1468, 194, and 686 +/- a pooled SEM of 221 ng.ml-1.min for
      vehicle-vehicle, vehicle-quipazine, idazoxan-vehicle, and idazoxan-quipazine
      treatments, respectively). We conclude that two mechanisms in the central nervous
      system mediate 5-hydroxytryptaminergic receptor-stimulated secretion of growth
      hormone in cattle; one independent and another dependent on alpha 2-adrenergic
      receptors, possibly via regulation of basal growth hormone secretion. In
      contrast, alpha 2-adrenergic receptor-induced secretion of growth hormone occurs
      independently of 5-hydroxytryptaminergic receptors.

PMID- 8751995
TI  - Effect of route of administration and dose on diabetes-induced protection against
      cisplatin nephrotoxicity.
AB  - The kidneys of diabetic rats exhibit resistance to the actions of a variety of
      nephrotoxic chemicals. Using the streptozotocin (STZ) diabetic rat as a model,
      the experiments in this study examined the effect of the diabetic state on
      bioavailability, renal accumulation and renal toxicity following intraperitoneal
      (i.p.) and intravenous (i.v.) injection of cisplatin at various doses. Comparison
      of the areas under the plasma concentration versus time curves up to 220 min
      after cisplatin injection (5 mg/kg body wt) demonstrated that bioavailability of
      cisplatin was significantly impaired in STZ diabetic versus nondiabetic rats
      after the i.p. route of administration, but not after the i.v. route. Regardless
      of the route of cisplatin injection, both renal cortex platinum level and renal
      toxicity as quantified by blood urea nitrogen (BUN) increase, were significantly
      lower in STZ diabetic versus nondiabetic rats. Thus, while decreased
      bioavailability probably plays a role in the protection seen after i.p.
      injection, renal mechanisms must also be involved since protection was also noted
      after i.v. injection despite equal bioavailability. To determine whether the
      protection can be overcome by increasing the dose of cisplatin, renal platinum
      and BUN levels in STZ diabetics and nondiabetics were compared after i.p. and
      i.v. cisplatin injections at 2.5, 5, 7.5, and 10 mg/kg body wt. The results
      demonstrate that the diabetes-induced renal protection can be partially reversed
      by increased cisplatin dose, but only by the i.v. route. Reversal was accompanied
      by increased renal platinum accumulation. These results suggest that STZ diabetes
      alters the tubular cells in a manner that confers protection that more closely
      resembles tolerance than absolute inherent resistance to the nephrotoxic actions
      of cisplatin.

PMID- 8751996
TI  - Copper deficiency increases total protein and apolipoprotein A-I synthesis in the
      rat small intestine.
AB  - This study was designed to determine whether an enhanced intestinal synthesis of
      apolipoprotein (apo) A-I is associated with the hyperapolipoproteinemia observed
      in copper-deficient rats. Male weanling Sprague-Dawley rats were assigned to two
      dietary treatments, Cu deficient (0.6 ppm Cu) and Cu adequate (6.0 ppm Cu) for 6
      weeks. In vivo studies were then performed after rats were injected with a
      flooding dose of 150 microM [3H]phenylalanine (PHE, 50 microCi/ml/100 g body wt).
      Three rats from each treatment were sacrificed at 5, 10, 15, 30, and 60 min
      postinjection. The small intestine was rapidly rinsed and frozen in liquid N2. In
      vitro studies were performed by labeling freshly isolated 6-cm segments from
      duodenum, jejunum and ileum with [3H]PHE (33 microCi/ml, 49.7 Cl/mmol) in PHE
      free minimum essential medium for 7 and 14 min. In vivo and in vitro intestinal
      samples were sonicated, solubilized in 1% Triton X-100, and centrifuged to
      provide the detergent soluble fraction for the isolation of nascent apo A-I and
      total protein. Radioactivities associated with nascent apo A-I isolated by
      immunoprecipitation and SDS-PAGE, and with total protein precipitated by
      trichloroacetic acid, were measured to determine the influence of Cu deficiency
      on nascent apo A-I and total protein synthesis. In the Cu-deficient small
      intestine, the synthesis of total protein was measured only in the duodenum and
      was enhanced after 1 hr for the in vivo studies. Moreover, total protein
      synthesis was enhanced at both 7 and 14 min of the in vitro studies for all three
      small intestinal segments of the Cu-deficient rats. Apo A-I synthesis was
      measured only at the jejunum and was also enhanced by Cu deficiency in the in
      vitro studies. Thus, an increase in intestinal apo A-I synthesis may contribute
      to the elevated plasma apo A-I level in Cu-deficient rats.

PMID- 8751997
TI  - Lipopolysaccharide alters aggrecan metabolism in the growth plate.
AB  - In this study, we examined the influence of lipopolysaccharide (LPS) on aggrecan
      metabolism and structure in the growth plate. Two experimental approaches were
      used: (i) in vivo administration of LPS to 10-day-old chicks; and (ii) in vitro
      addition of LPS to explant culture of normal chick growth plate. Twelve-day-old
      male broiler chicks were killed 48 hr after intravenous injection of LPS (3
      mg/kg) or saline (control), and growth plate from the femur or tibia was cultured
      or frozen. Tissue for explant culture was (i) cultured for 5 days with daily
      medium change (glycosaminoglycan release into the medium estimates proteoglycan
      breakdown rates), or (b) incubated with 35SO4 to determine the rate of
      proteoglycan synthesis. Proteoglycan structure was determined by associative (0.5
      M sodium acetate) and dissociative (4 M guanidine HCl) Sepharose CL2B
      chromatography. Explant culture of growth plate from LPS-injected chicks (in
      vivo) showed a decrease (P < 0.05) in the rate of proteoglycan synthesis. There
      were a greater proportion of small monomers and a reduced ability to aggregate in
      growth plate from LPS-injected chicks. In vitro addition of LPS (100
      micrograms/ml) to explant culture medium reduced proteoglycan synthesis (P <
      0.02), and the rate of release was increased (P < 0.001). In addition, the total
      and newly synthesized proteoglycans released into the medium from LPS-treated
      explant culture had a reduced aggregation and a majority of monomers that were
      smaller than control. These results demonstrate that LPS disrupts the normal
      metabolism and structure of growth plate aggrecan, and we hypothesize that this
      may adversely influence longitudinal growth.

PMID- 8751998
TI  - Mitochondrial mismatch analysis is insensitive to the mutational process.
AB  - Mismatch distributions are histograms showing the pattern of nucleotide (or
      restriction) site differences between pairs of individuals in a sample. They can
      be used to test hypotheses about the history of population size and subdivision
      (if selective neutrality is assumed) or about selection (if a constant population
      size is assumed). Previous work has assumed that mutations never strike the same
      site twice, an assumption that is called the model of infinite sites.
      Fortunately, the results are surprisingly robust even when this assumption is
      violated. We show here that (1) confidence regions inferred using the infinite
      sites model differ little from those inferred using a model of finite sites with
      uniform site-specific mutation rates, and (2) even when site-specific mutation
      rates follow a gamma distribution, confidence regions are little changed until
      the gamma shape parameter falls well below its plausible range, to roughly 0.01.
      In addition, we evaluate and reject the proposition that mismatch waves are
      produced by pooling data from several subdivisions of a structured population.

PMID- 8751999
TI  - Phylogenetic evidence for horizontal transmission of group I introns in the
      nuclear ribosomal DNA of mushroom-forming fungi.
AB  - Group I introns were discovered inserted at the same position in the nuclear
      small-subunit ribosomal DNA (nuc-ssu-rDNA) in several species of
      homobasidiomycetes (mushroom-forming fungi). Based on conserved intron sequences,
      a pair of intron-specific primers was designed for PCR amplification and
      sequencing of intron-containing rDNA repeats. Using the intron-specific primers
      together with flanking rDNA primers, a PCR assay was conducted to determine
      presence or absence of introns in 39 species of homobasidiomycetes. Introns were
      confined to the genera Panellus, Clavicorona, and Lentinellus. Phylogenetic
      analyses of nuc-ssu-rDNA and mitochondrial ssu-rDNA sequences suggest that
      Clavicorona and Lentinellus are closely related, but that Panellus is not closely
      related to these. The simplest explanation for the distribution of the introns is
      that they have been twice independently gained via horizontal transmission, once
      on the lineage leading to Panellus, and once on the lineage leading to
      Lentinellus and Clavicorona. BLAST searches using the introns from Panellus and
      Lentinellus as query sequences retrieved 16 other similar group I introns of nuc
      ssu-rDNA and nuclear large-subunit rDNA (nuc-lsu-rDNA) from fungal and green
      algal hosts. Phylogenetic analyses of intron sequences suggest that the mushroom
      introns are monophyletic, and are nested within a clade that contains four other
      introns that insert at the same position as the mushroom introns, two from
      different groups of fungi and two from green algae. The distribution of host
      lineages and insertion sites among the introns suggests that horizontal and
      vertical transmission, homing, and transposition have been factors in intron
      evolution. As distinctive, heritable features of nuclear rDNAs in certain
      lineages, group I introns have promise as phylogenetic markers. Nevertheless, the
      possibility of horizontal transmission and homing also suggest that their use
      poses certain pitfalls.

PMID- 8752000
TI  - Phylogenetic evidence from the IRBP gene for the paraphyly of toothed whales,
      with mixed support for Cetacea as a suborder of Artiodactyla.

PMID- 8752001
TI  - Large differences in substitutional pattern and evolutionary rate of 12S
      ribosomal RNA genes.
AB  - We demonstrate using Drosophila, periodical cicadas, and hominid primates, that
      the molecular clock based on animal mitochondrial small-subunit (12S) rRNA genes
      ticks at significantly different relative rates depending on which taxa and which
      region of the gene are examined. Drosophila, which are commonly used as model
      taxa, are evolving in a highly peculiar manner with the majority of sites in the
      3' half of the 12S gene apparently invariant. The analogous 3' half of the
      mitochondrial large-subunit rRNA gene (16S) appears to be similarly constrained.
      It is surprising that these regions that are already highly constrained in all
      animals should be even more constrained in Drosophila, especially when the
      Drosophila mitochondrial genome as a whole does not display a similar rate
      slowdown. This extreme 12S rate slowdown is not apparent in periodical cicadas or
      hominid primates and appears to be related to strong structural and functional
      constraints rather than a depressed mutation rate. Finally, the slow average rate
      of evolution in the third domain of Drosophila does not imply that the few
      variable sites lack multiple hits.

PMID- 8752002
TI  - Phylogenetic performance of mitochondrial protein-coding genes in resolving
      relationships among vertebrates.
AB  - A large number of studies in evolutionary biology utilize phylogenetic
      information obtained from mitochondrial DNA. Researchers place trust in this
      molecule and expect it generally to be a reliable marker for addressing questions
      ranging from population genetics to phylogenies among distantly related lineages.
      Yet, regardless of the phylogenetic method and weighting treatment, individual
      mitochondrial genes might potentially produce misleading evolutionary inferences
      and hence might not constitute an adequate representation neither of the entire
      mitochondrial genome nor of the evolutionary history of the organisms from which
      they are derived. We investigated the performance of all mitochondrial protein
      coding genes to recover two expected phylogenies of tetrapods and mammals.
      According to these tests, mitochondrial protein-coding genes can be roughly
      classified into three groups of good (ND4, ND5, ND2, cytb, and COI), medium
      (COII, COIII, ND1, and ND6), and poor (ATPase 6, ND3, ATPase 8, and ND4L)
      phylogenetic performers in recovering these expected trees among phylogenetically
      distant relatives. How general our findings are is unclear. Simple length
      differences and rate differences between these genes cannot account for their
      different phylogenetic performance. The phylogenetic performance of these
      mitochondrial genes might depend on various factors that play a role in
      determining the probability of discovering the correct phylogeny such as the
      density of lineage creation events in time, the phylogenetic "depth" of the
      question, lineage-specific rate heterogeneity, and the completeness of taxa
      representation.

PMID- 8752003
TI  - The apportionment of dinucleotide repeat diversity in Native Americans and
      Europeans: a new approach to measuring gene identity reveals asymmetric patterns
      of divergence.
AB  - The purpose of this paper is to assess the extent of gene identity and
      differentiation at 33 dinucleotide repeat loci (377 total alleles) within and
      among three European and three Native American populations. In order to do this,
      we show that a maximum-likelihood method proposed for phylogenetic trees (Cavalli
      Sforza and Piazza 1975) can be used to estimate gene identity (Nei 1987) with
      respect to any hierarchical structure. This method allows gene differentiation to
      be evaluated with respect to any internal node of a hierarchy. It also allows a
      generalization of F- and G-statistics to situations with unequal expected levels
      of differentiation. Our principal finding is that levels of genetic
      differentiation are unique to specific populations and levels of nesting. The
      populations of European origin show very little internal differentiation;
      moreover, their continental average is close to the total population defined by
      the aggregate of Europeans and Native Americans. By contrast, the Native American
      populations show moderate levels of internal differentiation, and a great
      distance between their continental average and the total. The results of analyses
      of subsets of loci that were selected to have high gene diversities in either
      Europeans or Native Americans closely parallel those from the total set of loci.
      This suggests that the principal results are unlikely to be caused by a European
      ascertainment bias in locus selection. In summary, our findings demonstrate that
      partitions of gene diversity into within- and between-populations components are
      heavily biased by the populations analyzed and the models fitted. Optimistically,
      however, more information is available to analyze population history and
      evolution by quantifying, as we have done, the uniqueness of patterns of
      differentiation.

PMID- 8752004
TI  - Evidence from milk casein genes that cetaceans are close relatives of
      hippopotamid artiodactyls.
AB  - The inferred transition from terrestrial hoofed mammal to fully aquatic cetacean
      has been intensively studied with fossil evidence. However, large sections of
      this remarkable evolutionary sequence are missing. Phylogenetic analysis of
      extant taxa may help to fill in some of these gaps. In this report, kappa-casein
      (exon 4) and beta-casein (exon 7) milk protein genes from cetaceans and other
      placental mammals were PCR-amplified, sequenced, and aligned to previously
      published sequences. Phylogenetic analyses of the casein data suggest that
      hippopotamid artiodactyls are more closely related to cetaceans than to other
      artiodactyls (even-toed hoofed mammals). An analysis of the nuclear casein
      sequences combined with published mitochondrial cytochrome b DNA sequences also
      supports the Cetacea/Hippopotamidae sister group. This affinity implies that some
      of the aquatic traits of cetaceans were derived in the common ancestor of Cetacea
      and Hippopotamidae. An extant "missing link" to Cetacea may have been overlooked
      by science since the description of the semiaquatic Hippopotamus in 1758.
      Paleontological information is grossly inconsistent with this hypothesis. If the
      casein phylogeny is accurate, large gaps in the fossil record as well as
      extensive morphological reversals and convergences must be acknowledged.

PMID- 8752005
TI  - Phylogenetic analysis of carbamoylphosphate synthetase genes: complex
      evolutionary history includes an internal duplication within a gene which can
      root the tree of life.
AB  - Carbamoylphosphate synthetase (CPS) catalyzes the first committed step in
      pyrimidine biosynthesis, arginine biosynthesis, or the urea cycle. Organisms may
      contain either one generalized or two specific CPS enzymes, and these enzymes may
      be heterodimeric (encoded by linked or unlinked genes), monomeric, or part of a
      multifunctional protein. In order to help elucidate the evolution of CPS, we have
      performed a comprehensive phylogenetic analysis using the 21 available complete
      CPS sequences, including a sequence from Sulfolobus solfataricus P2 which we
      report in this paper. This is the first report of a complete CPS gene sequence
      from an archaeon, and sequence analysis suggests that it encodes an enzyme
      similar to heterodimeric CPSII. We confirm that internal similarity within the
      synthetase domain of CPS is the result of an ancient gene duplication that
      preceded the divergence of the Bacteria, Archaea, and Eukarya, and use this
      internal duplication in phylogenetic tree construction to root the tree of life.
      Our analysis indicates with high confidence that this archaeal sequence is more
      closely related to those of Eukarya than to those of Bacteria. In addition to
      this ancient duplication which created the synthetase domain, our phylogenetic
      analysis reveals a complex history of further gene duplications, fusions, and
      other events which have played an integral part in the evolution of CPS.

PMID- 8752006
TI  - Nuclear-encoded rDNA group I introns: origin and phylogenetic relationships of
      insertion site lineages in the green algae.
AB  - Group I introns are widespread in eukaryotic organelles and nuclear-encoded
      ribosomal DNAs (rDNAs). The green algae are particularly rich in rDNA group I
      introns. To better understand the origins and phylogenetic relationships of green
      algal nuclear-encoded small subunit rDNA group I introns, a secondary structure
      based alignment was constructed with available intron sequences and 11 new
      subgroup ICI and three new subgroup IB3 intron sequences determined from members
      of the Trebouxiophyceae (common phycobiont components of lichen) and the
      Ulvophyceae. Phylogenetic analyses using a weighted maximum-parsimony method
      showed that most group I introns form distinct lineages defined by insertion
      sites within the SSU rDNA. The comparison of topologies defining the phylogenetic
      relationships of 12 members of the 1512 group I intron insertion site lineage
      (position relative to the E. coli SSU rDNA coding region) with that of the host
      cells (i.e., SSU rDNAs) that contain these introns provided insights into the
      possible origin, stability, loss, and lateral transfer of ICI group I introns.
      The phylogenetic data were consistent with a viral origin of the 1512 group I
      intron in the green algae. This intron appears to have originated, minimally,
      within the SSU rDNA of the common ancestor of the trebouxiophytes and has
      subsequently been vertically inherited within this algal lineage with loss of the
      intron in some taxa. The phylogenetic analyses also suggested that the 1512
      intron was laterally transferred among later-diverging trebouxiophytes; these
      algal taxa may have coexisted in a developing lichen thallus, thus facilitating
      cell-to-cell contact and the lateral transfer. Comparison of available group I
      intron sequences from the nuclear-encoded SSU rDNA of phycobiont and mycobiont
      components of lichens demonstrated that these sequences have independent origins
      and are not the result of lateral transfer from one component to the other.

PMID- 8752007
TI  - The divergent domains of the NEFA and nucleobindin proteins are derived from an
      EF-hand ancestor.
AB  - The human protein NEFA (DNA binding, EF-hand, Acidic region) has previously been
      isolated from a KM3 cell line and immunolocalized on the plasma membrane, in the
      cytoplasma, and in the culture medium. Sequence analysis of a cDNA clone encoding
      NEFA identified a hydrophilic domain, two EF-hands, and a leucine zipper at the C
      terminus. These characters are shared with nucleobindin (Nuc). In this paper we
      have further characterized NEFA and probed its evolutionary origins. Circular
      dichroism (CD) spectra of recombinant NEFA indicated a helical content of 51% and
      showed that the EF-hands are capable of binding Ca2+. Experiments with
      recombinant NEFA and synthesized peptides revealed that the leucine zipper cannot
      form a homodimer. The leucine zipper may allow heterodimer formation of NEFA and
      an unknown protein. Phylogenetic analyses suggest that this protein is derived
      from a four-domain EF-hand ancestor with subsequent duplications and fusions. The
      leucine zipper and putative DNA-binding domains of NEFA have evolved secondarily
      from existing EF-hand sequences. These analyses provide insights into how complex
      proteins may originate and trace the precursor of NEFA to the common ancestor of
      eukaryotes.

PMID- 8752009
TI  - Evolution of mammalian X-linked and autosomal Pgk and Pdh E1 alpha subunit genes.
AB  - The phylogeny and substitution rates of the mammalian X chromosome-located and
      autosomal phosphoglycerate kinase and pyruvate dehydrogenase genes were
      investigated. Compatibility analysis was used to show reticulate evolution in
      these genes. Analysis of the marsupial, mouse, and human phosphoglycerate kinase
      genes suggests that at least two recombination events have taken place, one
      occurring about the time of the placental-marsupial split involving exons 1-5 and
      the other before the primate-rodent split involving exons 9-10. Similar analysis
      of the pyruvate dehydrogenase genes indicates a recombination event involving
      exons 2-3 at a time before the primate-rodent split and a gene conversion between
      exons 3-4 in the human somatic and testis-specific pyruvate dehydrogenase genes
      after the primate-rodent split. This demonstrates that genetic exchange can occur
      between paralogous genes at widely separated chromosomal locations. Estimation of
      nucleotide substitution rates in these genes confirmed a higher substitution rate
      in the pyruvate dehydrogenase genes. In the phosphoglycerate kinase genes, there
      is no difference between the substitution rates in mice and humans and between
      the X chromosome- and autosome-located genes. A greater substitution rate was
      noted in the mouse autosomal pyruvate dehydrogenase gene when compared with the
      other mouse and human genes. This may be a result of either directional natural
      selection or a relaxation of functional constraint at this specific gene.

PMID- 8752008
TI  - A molecular and evolutionary study of the beta-globin gene family of the
      Australian marsupial Sminthopsis crassicaudata.
AB  - Beta-globin gene families in eutherians (placental mammals) consist of a set of
      four or more developmentally regulated genes which are closely linked and, in
      general, arranged in the order 5'-embryonic/fetal genes-adult genes-3'. This
      cluster of genes is proposed to have arisen by tandem duplication of ancestral
      beta-globin genes, with the first duplication occurring 200 to 155 MYBP just
      prior to a period in mammalian evolution when eutherians and marsupials diverged
      from a common ancestor. In this paper we trace the evolutionary history of the
      beta-globin gene family back to the origins of these mammals by molecular
      characterization of the beta-globin gene family of the Australian marsupial
      Sminthopsis crassicaudata. Using Southern and restriction analysis of total
      genomic DNA and bacteriophage clones of beta-like globin genes, we provide
      evidence that just two functional beta-like globin genes exist in this marsupial,
      including one embryonic-expressed gene (S.c-epsilon) and one adult-expressed gene
      (S.c-beta), linked in the order 5'-epsilon-beta-3'. The entire DNA sequence of
      the adult beta-globin gene is reported and shown to be orthologous to the adult
      beta-globin genes of the North American marsupial Didelphis virginiana and
      eutherian mammals. These results, together with results from a phylogenetic
      analysis of mammalian beta-like globin genes, confirm the hypothesis that a two
      gene cluster, containing an embryonic- and an adult-expressed beta-like globin
      gene, existed in the most recent common ancester of marsupials and eutherians.
      Northern analysis of total RNA isolated from embryos and neonatals indicates that
      a switch from embryonic to adult gene expression occurs at the time of birth,
      coinciding with the transfer of the marsupial from a uterus to a pouch
      environment.

PMID- 8752010
TI  - Higher ribosomal RNA substitution rates in Bacillariophyceae and Dasycladales
      than in Mollusca, Echinodermata, and Actinistia-Tetrapoda.
AB  - Molecular evolutionary rates within two protistan and three metazoan taxa were
      estimated using divergence times derived from fossil records. The results
      indicate that the small-subunit rRNA sequences within Dasycladales (Chlorophyta)
      and Bacillariophyceae evolved at a rate approximately two to three times faster
      than that estimated within Echinodermata, Mollusca, and Actinistia-Tetrapoda. It
      was concluded that this twofold discrepancy demonstrates actual taxonomic
      differences in the fixation rate of mutations in the small-subunit rRNA.

PMID- 8752011
TI  - The amino acid sequences of two alpha chains of hemoglobins from Komodo dragon
      Varanus komodoensis and phylogenetic relationships of amniotes.
AB  - To elucidate phylogenetic relationships among amniotes and the evolution of alpha
      globins, hemoglobins were analyzed from the Komodo dragon (Komodo monitor lizard)
      Varanus komodoensis, the world's largest extant lizard, inhabiting Komodo
      Islands, Indonesia. Four unique globin chains (alpha A, alpha D, beta B, and beta
      C) were isolated in an equal molar ratio by high performance liquid
      chromatography from the hemolysate. The amino acid sequences of two alpha chains
      were determined. The alpha D chain has a glutamine at E7 as does an alpha chain
      of a snake, Liophis miliaris, but the alpha A chain has a histidine at E7 like
      the majority of hemoglobins. Phylogenetic analyses of 19 globins including two
      alpha chains of Komodo dragon and ones from representative amniotes showed the
      following results: (1) The a chains of squamates (snakes and lizards), which have
      a glutamine at E7, are clustered with the embryonic alpha globin family, which
      typically includes the alpha D chain from birds; (2) birds form a sister group
      with other reptiles but not with mammals; (3) the genes for embryonic and adult
      types of alpha globins were possibly produced by duplication of the ancestral
      alpha gene before ancestral amniotes diverged, indicating that each of the
      present amniotes might carry descendants of the two types of alpha globin genes;
      (4) squamates first split off from the ancestor of other reptiles and birds.

PMID- 8752012
TI  - Molecular phylogeny of macaques: implications of nucleotide sequences from an 896
      base pair region of mitochondrial DNA.
AB  - We determined the nucleotide sequences of an 896-base pair region of
      mitochondrial DNA (mtDNA) from 20 primates representing 13 species of macaques, a
      baboon, and a patas. We compared these sequences and the homologous sequences
      from four macaques and a human against each other and deduced the phylogenetic
      relationships of macaques. The results from the phylogenetic analyses revealed
      five groups among the macaques: (1) Barbary macaque, (2) two species of Sulawesi
      macaques, (3) Japanese, rhesus, Taiwanese, crab-eating, and stump-tailed
      macaques, (4) toque, pig-tailed, and lion-tailed macaques, and (5) Assamese and
      bonnet macaques. The phylogenetic position of Tibetan macaque remains ambiguous
      as to whether it belongs to the fourth or fifth group. Phylogenetic trees
      revealed that Barbary macaque diverged first from the other Asian macaques.
      Subsequently, the four groups of Asian macaques diverged from one another in a
      relatively short period of time. Within each group, most of the species diverged
      in a relatively short period of time following the divergence of the groups.
      Assuming that the Asian macaques diverged from the outgroup Barbary macaque three
      million years ago (MYA), the divergence times among groups of Asian macaques were
      estimated at 2.1-2.5 MYA and within groups at 1.4-2.2 MYA. The intraspecific
      nucleotide diversity observed among three rhesus macaques was so large that they
      did not form a monophyletic cluster in the phylogenetic trees. Instead, one of
      them formed a cluster with Japanese and Taiwanese macaques, whereas the other two
      formed a separate cluster. This implies that either polymorphisms of mtDNA
      sequences that existed before the divergence of these three species (ca. 700,000
      years ago) have been retained in rhesus macaques or introgression has occurred
      among the three species.

PMID- 8752013
TI  - Relative rates of nuclear DNA evolution in human and Old World monkey lineages.
AB  - Rates of substitution were compared between humans and Old World monkeys for
      sequences in or adjacent to 19 genes. The comparison of 21,299 sites in noncoding
      regions indicates that the substitution rate is approximately 43% greater in the
      Old World monkey lineage. However, 83% of the compared sites are in the region of
      the beta-globin gene family. Outside this region there is no consistent pattern
      of rate difference between the two lineages. Comparison of the coding regions of
      16 genomically dispersed genes, involving 1,592 synonymous sites and 5,275
      nonsynonymous sites, showed a faster rate of substitution in the human lineage at
      the nonsynonymous sites of the prion gene, but otherwise no evidence of rate
      difference between the two lineages. It is concluded that rate differences
      between these two lineages may be specific to certain regions of the genome
      rather than being a general phenomenon. This conclusion needs to be confirmed by
      comparison of a larger number of genomically dispersed sequences. It is, however,
      consistent with the results of DNA-DNA hybridization experiments, which show no
      difference in evolutionary rate between the two lineages.

PMID- 8752014
TI  - Impact of a smoking ban on a locked psychiatric unit.
AB  - BACKGROUND: This study prospectively evaluated the impact of a complete smoking
      ban on a locked psychiatric unit. METHOD: The setting was a 16-bed inpatient unit
      with 83% (134/162) involuntary patients, no off-unit smoking area, no possibility
      of granting smoking passes, and a mean length of stay of 2 weeks. The effect of a
      complete smoking ban was measured by surveys of both staff and patients before
      and after the ban. In addition, objective indicators of ward disruption were
      measured, including rates of aggression, use of p.r.n. medications, need for
      seclusion and restraints, elopement, and discharges against medical advice.
      RESULTS: Although staff initially expressed concern about the ban's potential
      negative impact, after it began, t tests revealed that staff were significantly
      (p < .05) less concerned about patients' needing more medication, becoming
      restless, being too fragile to cope with withdrawal, leaving the unit against
      medical advice, or trying to elope. Staff were significantly (p < .02) more
      positive about the ban than were patients. Although patients, overall, had
      negative views toward the new policy, their opinions were somewhat less negative
      after its implementation. Rates of assaultive behavior, use of seclusion and
      restraints, use of p.r.n. medication, and against-medical-advice or elopement
      discharges did not change after the ban was in effect. When polled, 78% (40/51)
      of the staff voted to keep the ban. CONCLUSION: This study found that staff
      anticipated negative consequences to a total smoking ban; however, their
      attitudes changed after it began. The ban had no significant impact on the ward
      milieu, and although patients were not in favor of it, they felt less negative
      over time.

PMID- 8752016
TI  - Effect of fluvoxamine on total serum cholesterol levels during weight reduction.
AB  - BACKGROUND: The effect of fluvoxamine versus placebo on serum cholesterol levels
      in obese women undergoing behavior therapy for weight reduction was evaluated.
      METHOD: Forty obese female outpatients undergoing 13 weeks of a behaviorally
      oriented treatment program for weight reduction were randomly assigned to double
      blind treatment with fluvoxamine 100 mg/day (N = 18) or placebo (N = 22). Total
      serum cholesterol levels were measured before and after the 13-week study period.
      RESULTS: Patients of the two treatment groups did not differ in age, weight, body
      mass index, cholesterol levels before treatment, and the extent of weight
      reduction during treatment. Cholesterol levels were significantly lower after
      fluvoxamine treatment than before, whereas cholesterol levels remained unaltered
      after placebo administration. Patients with initially high total cholesterol
      levels (> or = 200 mg/dL) showed a significantly larger reduction than patients
      with desirable cholesterol levels. However, there was no interaction between
      treatment and initial cholesterol level. CONCLUSION: The results might suggest a
      cholesterol-lowering effect of fluvoxamine.

PMID- 8752015
TI  - A pharmacoeconomic model of outpatient antipsychotic therapy in "revolving door"
      schizophrenic patients.
AB  - BACKGROUND: The discrepancy between supply and demand in health care today
      requires that psychiatrists and other providers of patient care expand their
      traditional role from one of patient advocate to one of allocator of care. In
      this new role, the care provider must consider not only the efficacy and safety
      of a therapeutic regimen, but also its impact on society in terms of quality of
      life and cost-effectiveness. METHOD: A variety of pharmacoeconomic analysis
      methodologies have been used to assess the economic and quality of life
      consequences of alternate treatment strategies. A clinical decision analysis
      model that takes into account compliance rates and associated rehospitalization
      was used to compare the direct treatment costs associated with alternate
      outpatient neuroleptic strategies for "revolving door" schizophrenic patients.
      The antipsychotic treatment options considered were traditional oral neuroleptics
      (e.g., haloperidol), depot neuroleptics (e.g., haloperidol decanoate), and
      "atypical" oral agents (e.g., risperidone). RESULTS: The results of this decision
      analysis model (based on a set of reasonable outcome probabilities and costs)
      suggest that, under five sets of cost and outcome assumptions, switching to the
      depot route in a patient with a history of relapse and rehospitalization may
      reduce total direct treatment costs by approximately $650 to $2600/year compared
      with an atypical agent and approximately $460 to $1150/year compared with a
      traditional oral neuroleptic. Under a sixth set of assumptions-namely, a
      compliance rate with atypical oral drug (80%) equal to that with the depot agent
      and an average wholesale price of the atypical drug 25% lower than current
      wholesale price-the atypical oral drug treatment option would be approximately
      $700 less than treatment with a depot agent, and $1860 less than treatment with a
      traditional neuroleptic. CONCLUSION: The decision analysis model presented here
      indicates that, under a variety of assumptions, switching a revolving door
      patient to a depot medication for outpatient maintenance therapy could result in
      lower total direct treatment costs over the first year. This finding was
      consistent, although to varying degrees, under differing probability and cost
      assumptions. The proposed model can be used in other clinical circumstances, such
      as treatment-refractory patients or those with severe negative symptoms, as well
      as with other associated outcome probabilities and costs. Application of this
      model in different clinical scenarios associated with different outcome
      probabilities and treatment costs, however, may well provide different results.

PMID- 8752017
TI  - Diazepam versus alprazolam for the treatment of panic disorder.
AB  - BACKGROUND: Alprazolam has proven efficacy as a treatment for panic disorder, but
      the place of other benzodiazepines is less well established. METHOD: To compare
      the efficacy and tolerability of diazepam and alprazolam for the disorder, a
      placebo-controlled, double-blind trial was undertaken in two sites. Two hundred
      forty-one subjects with panic disorder or agoraphobia with panic attacks were
      randomly assigned to flexible doses of diazepam, alprazolam, or placebo for 8
      weeks. RESULTS: At the end of the trial, over 60% of subjects taking either
      diazepam or alprazolam were at least moderately improved compared with less than
      30% of those taking placebo. On all measures of efficacy, subjects taking
      diazepam and alprazolam showed an equally favorable response. Despite some
      sedation early in the trial, both drugs were tolerated well. More severely ill
      subjects responded less well to either benzodiazepine. CONCLUSION: The results
      indicate that diazepam is an effective alternative to alprazolam for the
      treatment of panic disorder.

PMID- 8752018
TI  - Lithium-associated cognitive and functional deficits reduced by a switch to
      divalproex sodium: a case series.
AB  - BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance
      treatment of bipolar disorder. Although much has been written about the
      management of the more common adverse effects of lithium, such as polyuria and
      tremor, more subtle lithium side effects such as cognitive deficits, loss of
      creativity, and functional impairments remain understudied. This report
      summarizes our experience in switching bipolar patients from lithium to
      divalproex sodium to alleviate such cognitive and functional impairments. METHOD:
      Open, case series design. RESULTS: We report seven cases where substitution of
      lithium, either fully or partially, with divalproex sodium was extremely helpful
      in reducing the cognitive, motivational, or creative deficits attributed to
      lithium in our bipolar patients. CONCLUSION: In this preliminary report,
      divalproex sodium was a superior alternative to lithium in bipolar patients
      experiencing cognitive deficits, loss of creativity, and functional impairments.

PMID- 8752019
TI  - Pathological gambling in hospitalized substance abusing veterans.
AB  - BACKGROUND: Previous studies have suggested that pathological gambling and
      substance abuse may be more likely to occur together than expected by chance. We
      examined this possibility as well as explored psychosocial and diagnostic
      variables that may be associated with this coincidence. METHOD: Of 276 patients
      who were administered the South Oaks Gambling Screen, 134 subjects were
      interviewed using a semistructured comprehensive psychiatric questionnaire. Data
      analysis utilized Student t tests or analysis of variance routines. RESULTS: The
      rate of comorbid pathological gambling in the sample was 33% (92 of 276). A high
      rate of comorbid substance abuse and pathological gambling was associated with a
      positive history of childhood experiences of gambling in the family group (p =
      .001) and with larger family size (p = .001). In addition, current alcohol
      consumption was significantly higher (p = .007) in the pathological gambling
      group. CONCLUSION: Comorbidity of substance abuse and pathological gambling is
      common in substance abuse patients in a VA hospital. Substance abuse treatment
      programs should identify patients with pathological gambling and include
      treatment interventions that address both problems.

PMID- 8752020
TI  - Structured psychiatric interview and ambulatory sleep monitoring in young
      psychophysiological insomniacs.
AB  - BACKGROUND: The presence of psychiatric disorders (according to DSM-III-R), the
      discriminating power of a psychiatric structured interview, and sleep monitoring
      were investigated in psychophysiological insomnia. METHOD: Forty young (20-40
      years old) patients, selected for putative psychophysiological insomnia,
      underwent a psychiatric structured interview and home ambulatory sleep monitoring
      for 2 nights. The results were compared with those of a group of nine young
      normal sleepers. RESULTS: 48% of the insomniacs showed some psychiatric
      disorders, while 52% did not meet DSM-III-R criteria for a psychiatric diagnosis.
      Both groups, but not the controls, showed a slight first-night effect in the
      sleep analysis. The sleep structure of all insomniacs was found to be disturbed,
      mainly in sleep continuity, but essentially the two groups showed no significant
      differences. When we used a stepwise logistic regression analysis, the number of
      sleep stage shifts (indicating sleep instability) was the best variable in
      discriminating the insomniacs from controls, but not the patients with
      psychiatric disturbances from those without psychopathologies. CONCLUSION: The
      evaluation of young insomniacs with a structured psychiatric interview rather
      than with ambulatory sleep monitoring seems to be most useful in discriminating
      between patients with only psychophysiological insomnia and patients with both
      insomnia and an associated diagnosis of another mental disorder.

PMID- 8752021
TI  - The suppression of nightmares with guanfacine.

PMID- 8752022
TI  - Near syncope associated with concomitant clozapine and cocaine use.

PMID- 8752023
TI  - Zolpidem for the treatment of agitation in elderly demented patients.

PMID- 8752024
TI  - Critique of fluoxetine study in PTSD.

PMID- 8752025
TI  - Breakthrough panic after amantadine treatment in a Parkinson's disease patient.

PMID- 8752026
TI  - New perspectives in the management of depression. Symposium highlights from ECNP,
      Venice, September 1995.

PMID- 8752028
TI  - Upper dorsal thoracoscopic sympathectomy for palmar hyperhidrosis: improved
      intermediate-term results.
AB  - PURPOSE: The purpose of this study was to examine the immediate and mid-term
      results of thoracoscopic upper dorsal (T2-T3) sympathectomy for primary palmar
      hyperhidrosis. METHODS: From June 1993 to October 1994 we performed 106
      sympathectomies on 53 patients with palmar hyperhidrosis. Thirty-four female
      patients and 19 male patients ranging in age from 15 to 44 years, (mean 23.1
      years) were studied. Both sides were operated during the same surgical procedure.
      The T2-T3 ganglia were resected by electrocuting with a hook and were removed for
      histologic examination. Follow-up for a mean of 19.25 months was obtained on 52
      patients (104 operated limbs). RESULTS: All limbs were completely dry at the end
      of the procedure, and hyperhidrosis did not recur during the whole follow-up
      period. Short-term postoperative complications (mainly atelectasis, pneumonia,
      pneumothorax, and hemothorax) occurred in six (11.3%) patients. Long-term
      sequelae were observed in 43 (81.1%) patients and included Horner's syndrome (9
      patients, 17.3%, one side only in each patient), neuralgia (7 patients, 13.5%),
      and compensatory hyperhidrosis (35 patients, 67.3%). These sequelae were not
      permanent in all cases, and the degree of severity was variable. Six (11.5%)
      patients, three of whom regretted being operated, were dissatisfied with their
      results: one because of Horner's syndrome, one because of persisting neuralgia,
      and four because of compensatory sweating. CONCLUSIONS: Despite the large number
      of postoperative long-term sequelae, 88.5% of patients expressed subjective
      satisfaction from the procedure. Obtaining 100% of dry hands on mid-term follow
      up makes this approach rewarding.

PMID- 8752027
TI  - Inhibition of white blood cell adhesion at reperfusion decreases tissue damage in
      postischemic striated muscle.
AB  - PURPOSE: To determine the impact of white blood cell (WBC)-endothelium adhesion
      on tissue damage in the setting of ischemia-reperfusion injury in striated
      muscle. METHODS: The cremaster muscle of four groups of anesthetized Sprague
      Dawley rats was subjected to 4 hours of global, warm (37 degrees C) ischemia and
      2 hours of reperfusion. At reperfusion two groups of animals received intravenous
      injections of monoclonal antibodies directed against either CD11b/CD18 (1B6) or
      ICAM-1 (1A29). The remaining two groups of animals received saline injections
      (NoRx) or nonreactive IgG1. In vivo light microscopic techniques were used to
      determine WBC adherence (number of WBCs per 100 microns postcapillary venules) at
      different intervals of reperfusion. Muscle viability was assessed with computer
      assisted image analysis by measuring the optical intensity of transilluminated
      muscles after incubation with nitroblue tetrazolium. RESULTS: Our results (mean
      +/- SEM) demonstrate a significant increase in the number of adherent WBCs
      relative to baseline (8.0 +/- 0.5) after 4 hours of global ischemia in animals
      receiving NoRx or IgG1. The significant increase occurred at 30 minutes of
      reperfusion (17.6 +/- 0.6 and 17.4 +/- 0.4 for NoRx or IgG1, respectively) and
      was sustained for the duration of the experiment. This increase in adherence was
      attenuated by 1B6 and 1A29 (12.2 +/- 2.2 and 12.4 +/- 0.8, respectively; p < 0.05
      compared with NoRx and IgG1). The decrease in WBC adhesion was associated with a
      decrease in reperfusion injury to the muscle, as indicated by lower optical
      intensity values for the 1B6 and 1A29 groups (123 +/- 3 and 129 +/- 2) compared
      with the NoRx and IgG1 groups (151 +/- 2 and 158 +/- 4). CONCLUSIONS: Our data
      support an important role for WBCs in the pathogenesis of ischemia-reperfusion
      injury. Interfering with the WBC-endothelium interactions by using monoclonal
      antibodies directed against WBCs and endothelial cell adhesion molecules may help
      to limit ischemia-reperfusion injury.

PMID- 8752029
TI  - Acute platelet deposition after carotid endarterectomy in sheep: vein patch
      compared with gelatin-sealed Dacron and polytetrafluoroethylene patch closure.
AB  - PURPOSE: Patch angioplasty is commonly used to close the arteriotomy after
      carotid endarterectomy is performed. The purpose of this study was to determine
      whether any significant variations were present in platelet deposition for
      different patch sizes and materials. METHOD: The study measured 111-indium
      labeled uptake in the sheep to compare thrombus deposition for three different
      patch materials: autologous vein, gelatin-sealed Dacron, and
      polytetrafluoroethylene and for 6- and 12-mm patch widths. Platelet uptake was
      measured on the patch itself and on the artery wall that was opposite to the
      patch and that had undergone endarterectomy. Scanning electron microscopy was
      used to confirm the localization of the labeled platelets on the patch and on the
      surface that had undergone endarterectomy. RESULTS: Although considerable
      variation was seen among animals, platelet accumulation was lowest in the vein
      patches compared with the prosthetic patches (p < 0.01), but the deposition on
      the gelatine-sealed Dacron was not significantly different from that on
      polytetrafluoroethylene patches. Platelet deposition on the artery wall that had
      undergone endarterectomy was considerably less than on the patch but was higher
      when a synthetic patch was used rather than a vein patch (p < 0.05). CONCLUSIONS:
      Acute thrombus deposition after carotid endarterectomy was considerably less for
      vein patch closure than for synthetic patches. A 6-mm patch width caused less
      thrombus deposition both on the patch itself and on the artery wall compared with
      a 12-mm patch, but the difference was proportional to the patch width.

PMID- 8752030
TI  - Management of recurrent carotid stenosis: should asymptomatic lesions be treated
      surgically?
AB  - PURPOSE: The purpose of this study was to determine factors that may influence
      patient selection for surgery in recurrent carotid stenosis (RCS) and to contrast
      the results of primary and secondary carotid endarterectomy (CENDX) with regard
      to operative morbidity and stroke prevention. METHODS: Forty-eight patients who
      underwent CENDX for RCS (RCS-OP group) were compared with a contemporaneous group
      of 40 patients who on at least one post-CENDX duplex ultrasonography study had a
      greater than 50% stenosis but did not undergo operation (RCS-NO-OP group). This
      latter group was drawn from 1053 follow-up duplex studies in 348 patients who
      underwent primary CENDX between the years 1983 and 1993. Each of these two groups
      was compared with a metanalysis of six key series derived from the literature.
      RESULTS: No significant differences were seen in the demographics or the
      incidence of risk factors between the two groups except for a higher incidence of
      coronary artery disease (p < 0.03) and peripheral vascular disease (p < 0.001) in
      the RCS-OP group. The operation-specific stroke rate was 2.1%, and the 30-day
      mortality was also 2.1%. Symptomatic RCS was the indication in 56% of cases.
      Important anatomic differences were found between groups. The
      duplex/arteriographic degree of stenosis was greater than 90% in 75% of the
      patients in the RCS-OP group, whereas only 10% of the patients in the RCS-NO-OP
      group had greater than 80% stenosis, most being in the 50% to 80% range. An
      unexpected finding was the sudden progression to occlusion in 10 (25%) of 40 in
      the RCS-NO-OP group, with 2 (5%) of 10 of the occlusions presenting as unheralded
      strokes. Overall, a stroke without an antecedent transient ischemic attack
      occurred in 3 (7.5%) of 40 of patients in the RCS-NO-OP group, all in patients
      with greater than 75% stenosis on their last documented scan preceding the
      stroke. CONCLUSION: Given the relatively low stroke rate with surgery in the RCS
      OP group (2.1%) and the higher incidence of unheralded strokes (7.5%) in the RCS
      NO-OP group, a more aggressive approach may be warranted in patients with
      asymptomatic high-grade (> 75%) RCS, a strategy not unlike that adopted for
      primary CENDX.

PMID- 8752031
TI  - Intraoperative salvage in patients undergoing elective abdominal aortic aneurysm
      repair: an analysis of cost and benefit.
AB  - PURPOSE: Although autologous blood procurement has become a standard of care in
      elective surgery, recent studies have questioned its cost-effectiveness. We
      therefore reviewed our 3-year experience with intraoperative cell salvage in
      patients who underwent elective abdominal aortic aneurysm repair. METHODS: A 3
      year retrospective chart review of elective abdominal aortic aneurysm (infrarenal
      and suprarenal) repair was performed. Transthoracic repairs were excluded.
      RESULTS: Estimated blood lost was 1748 +/- 1236 ml, or 35% of baseline blood
      volume (5012 +/- 689 ml). Overall, 164 (89%) received red blood cell (RBC)
      transfusions (3.5 +/- 2.0 U/patient). The cost per patient for cell salvage was
      $315 +/- $97, representing 31% of all RBC costs and 24% of total blood component
      costs. Mean salvage volume infused was 578 +/- 600 ml; at a mean hematocrit level
      of 55.7% the RBC volume infused from salvage during surgery was 313 +/- 328 ml
      (representing 27% of total RBC volume lost during the hospital stay). This mean
      RBC volume salvaged represented the equivalent of 1.6 blood bank RBC units. The
      mean blood bank costs saved by using cell salvage was $248, or 79% of the $315
      actually spent for salvage. We found no decrease in percentage of patients
      undergoing transfusion until salvage volumes that were infused exceeded 750 ml,
      or the equivalent of two blood bank units; all of these patients who benefitted
      had estimated blood lost > or = 1000 ml. CONCLUSIONS: We conclude that use of
      intraoperative cell salvage was most beneficial for patients who had estimated
      blood loss greater than or equal to 1000 ml and cell salvage volumes infused
      greater than or equal to 750 ml. Patients who are estimated to lose less than
      1000 ml receive little benefit yet incur substantial costs from intraoperative
      cell salvage.

PMID- 8752032
TI  - Value of single photon emission computerized imaging in the treatment of patients
      undergoing carotid endarterectomy.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical relevance of
      regional cerebral blood flow by single photon emission computerized imaging
      (SPECT) in patients undergoing carotid endarterectomy (CEA). METHOD: Eighty-four
      patients were included in this study; 74 were undergoing CEA. All 74 operative
      cases had SPECT scans before and after surgery. The first 30 patients undergoing
      CEA also had computed tomography scans for comparison. Findings were correlated
      during surgery with carotid stump pressures. RESULTS: No deaths and no strokes
      occurred. Four complications were seen. In the first 30 patients with computed
      tomography scans, 20 had positive SPECT scans, whereas the computed tomography
      scan was negative. A 100% linear correlation was seen with operative stump
      pressures, and decreased regional cerebral blood flow was noted on SPECT scan
      before surgery (48 abnormal with mean 26 mm). These patients received shunts
      during CEA. CONCLUSION: SPECT scans add useful physiologic data to anatomic
      images and provide factual or objective information that is valuable in treating
      patients undergoing CEA. A positive SPECT scan is predictive of poor collateral
      circulation and may possibly identify those "at risk," if they have no symptoms,
      and those who will require shunting during surgery. SPECT scans may facilitate
      case selection in severe bilateral carotid stenosis and deferment of operation in
      elderly patients at high risk. After surgery SPECT scans will document the value
      of successful CEA in reestablishing normal regional cerebral blood flow. Finally,
      SPECT scans have potential value for reevaluating patients who have complete
      carotid occlusion for external carotid/internal carotid artery bypass.

PMID- 8752033
TI  - Cultured human endothelial cells seeded on expanded polytetrafluoroethylene
      support thrombin-mediated activation of protein C.
AB  - PURPOSE: Reduction of the thrombogenicity of synthetic vascular grafts by
      endothelialization has been suggested. The purpose of this study was to examine
      some of the non-thrombogenic properties of cultured adult human great saphenous
      vein endothelial cells seeded on expanded polytetrafluoroethylene (ePTFE) grafts.
      METHODS: Endothelialized grafts, control grafts, and wells were incubated with
      thrombin. Assays of thrombin loss from solution, thrombin coagulant activity, and
      protein C activation on the surface were obtained. The presence of thrombomodulin
      was confirmed with immunohistochemistry. RESULTS: Significantly more thrombin was
      found on the ePTFE grafts or wells that underwent endothelialization, and larger
      amounts were lost from the thrombin solution compared with the control group.
      Thrombin enzyme activity on the endothelialization group was almost completely
      represented by activation of protein C and only to a minor extent by activity
      towards fibrinogen. CONCLUSIONS: It is concluded that endothelial cells seeded on
      ePTFE retain the possibility to inhibit thrombin coagulant activity and to
      activate protein C. These findings provide support for the clinical applicability
      of cultured autologous endothelium on ePTFE grafts.

PMID- 8752034
TI  - Selective use of the intensive care unit after nonaortic arterial surgery.
AB  - PURPOSE: The purpose of this study was to determine whether the institution of a
      clinical protocol combining 6 hours of recovery room observation and guidelines
      for intensive care unit (ICU) admission would allow selected patients to be
      safely transferred directly to a surgical floor after nonaortic arterial
      reconstruction. METHODS: After a clinical pathway was formed, 134 consecutive
      patients undergoing 154 nonaortic arterial operations were prospectively enrolled
      in this study. Patients requiring ICU care and the responsible factors were
      identified. Comparisons of risk factors and demographics were made between those
      patients who did and did not require ICU care. RESULTS: Twelve (7.8%) patients
      spent a total of 27 days in the ICU (range 1 to 11 days). As per our guidelines
      four patients were transferred to the ICU for invasive monitoring, and four were
      sent to the ICU because of refractory hemodynamic instability or arrhythmia in
      the postanesthetic recovery room. An additional four patients were transferred to
      the ICU after having been on the surgical floor for 24 to 72 hours because of the
      following perioperative complications: prolonged chest pain (one), pneumonia
      (one), heart failure (one), and graft occlusion requiring a urokinase infusion.
      Patients admitted to the ICU were more likely to have heart disease (p = 0.02)
      and to have had an operation other than carotid endarterectomy (p = 0.04) than
      those who were not. The 30-day mortality rate was 1.4%. CONCLUSIONS: The
      implementation of a clinical protocol similar to the one used in this study will
      allow many patients undergoing nonaortic vascular surgery to avoid the use of the
      ICU. This approach will conserve hospital and financial resources without
      adversely affecting patient morbidity and mortality rates.

PMID- 8752035
TI  - Improved method to create the common ostium variant of the distal arteriovenous
      fistula for enhancing crural prosthetic graft patency.
AB  - PURPOSE: Successful use of the distal adjunctive arteriovenous fistula (dAVF) for
      the enhancement of prosthetic graft patency rates in the crural position is
      critically dependent on the qualitative and quantitative aspects of the arterial
      and venous runoff. Precise technical performance of the fistula is equally vital
      to secure optimal results. The purpose of this study was to determine current
      prosthetic graft patency and limb salvage rates using a modified version of the
      common ostium dAVF. METHODS: The standard method to create the common ostium
      variant of dAVF has been modified to improve apposition of the "otomy" sites of
      the artery and vein, avoid twisting and stenosis by terminating the fistula
      suture line at the artery-vein junctures, reshaping the ovoid ostium to a
      rectangular shape, and finally, use of multiple interrupted heel-toe sutures.
      RESULTS: Since 1979 we have created 290 fistulas in 281 patients who required leg
      revascularization procedures. In different time periods we have documented
      improving graft patency and limb salvage rates. Fistula patency, reflected by
      annual attrition rates of 13% to 26% per year, continues as a challenge for long
      term results. Current 3-year secondary cumulative graft patency and limb salvage
      rates by life table analysis are 61% and 74%, respectively. The conduit material
      may play a role with regard to steal phenomena and the need for banding
      techniques. CONCLUSION: Configuration of the adjunctive dAVF may impact on
      prosthetic graft patency in the crural position. In addition, the type of graft
      material used for bypass may be instrumental in preventing or precipitating the
      steal phenomenon. These issues require further study to better understand flow
      dynamics, patterns of intimal hyperplasia, and blood distribution as a function
      of conduit material and impedance of the arterial and venous runoff.

PMID- 8752036
TI  - Blunt injury to the internal carotid artery at the base of the skull: six cases
      of venous graft restoration.
AB  - PURPOSE: Blunt injuries to the internal carotid artery (ICA) at the base of the
      skull are uncommon but potentially dangerous lesions whose management remains
      unclear. We report a new surgical approach of the intrapetrosal portion of the
      ICA that was used in six patients with the help of an ear, nose, and throat
      surgeon. METHODS: During a 70-month period, seven consecutive patients (four
      women, three men; mean age, 35.7 years; range, 21 to 59 years) were admitted, six
      after a motor vehicle accident and one after a cervical manipulation. All
      patients had a neurologic deficit. An arteriographic scan revealed four
      unilateral ICA lesions: two false aneurysms, one tight stenosis, and one
      dissection; two cases of bilateral ICA dissection were mentioned, and one case of
      ICA dissection was associated with a contralateral ICA thrombosis. RESULTS: One
      patient died before surgery, and six patients underwent a unilateral venous graft
      restoration, reaching the vertical portion of the intrapetrosal ICA in two
      patients and the horizontal portion in four. A shunt was used in one patient.
      Failure to recognize the end of the ICA lesion was responsible for one
      postoperative asymptomatic graft thrombosis (17%), but this difficulty was
      overcome by using intraoperative angioscopy in the other patients. No deaths and
      no new strokes were noted during postoperative and midterm follow-up (mean follow
      up, 34 months). Five postoperative facial pareses occurred and were totally
      regressive within 3 to 6 months in four patients; one total deafness was
      recorded. CONCLUSION: Venous graft restoration of traumatic ICA lesions at the
      base of the skull can safely be performed with such an approach, thus producing
      highly satisfactory results. Before undergoing surgery, the patient must be aware
      of the risk of facial and auditive disorders, which are generally temporary.

PMID- 8752037
TI  - Value of toe pulse waves in addition to systolic pressures in the assessment of
      the severity of peripheral arterial disease and critical limb ischemia.
AB  - PURPOSE: Although pressure measurements are useful in the assessment of the
      severity of the arterial obstruction, they do not completely identify limbs with
      and without critical limb ischemia. Our objective was to test whether addition of
      the measurements of toe pulse waves (PW), which depend on distal perfusion, to
      pressure measurements could improve the determination of the severity of arterial
      disease and the presence of critical limb ischemia. METHODS: We measured toe
      pressure (TSP) and ankle/brachial index (ABI) and recorded PW with
      photoplethysmography in 358 limbs of 182 patients. RESULTS: TSP, ABI, and PW
      amplitude were lower in 67 limbs with rest pain, skin lesions, or both, with mean
      differences of 29 mm Hg, 0.12, and 16 mm, respectively (p < 0.01). Similarly, in
      the subgroup of 107 limbs with TSP < or = 30 mm Hg, TSP, and PW amplitude, but
      not ABI, were lower in 53 limbs with rest pain, skin lesions, or both, with mean
      differences of 10 mm Hg and 7 mm (p < 0.01). Multiple logistic regression showed
      that after controlling was done for TSP and ABI, the odds ratio for the presence
      of rest pain, skin lesions, or both associated with PW amplitude < or = 4 mm was
      4.3 (95% confidence interval 1.7, 11.0; p < 0.01). In the subgroup with TSP < or
      = 30 mm Hg, this odds ratio was 3.5 (95% confidence interval 1.0, 11.6; p <
      0.05). CONCLUSIONS: The findings indicate that addition of PW recording to
      pressure measurements is likely to increase the accuracy of assessment for
      critical limb ischemia.

PMID- 8752038
TI  - Role of magnetic resonance imaging in the diagnosis of osteomyelitis in diabetic
      foot infections.
AB  - PURPOSE: The role of magnetic resonance imaging (MRI) in the diagnosis of
      osteomyelitis in foot infections in diabetics was investigated. The accuracy,
      sensitivity, and specificity of MRI, plain radiography, and nuclear scanning were
      determined for diagnosing osteomyelitis, and a cost comparison was made. METHODS:
      Twenty-seven patients with diabetic foot infections were studied prospectively.
      All patients underwent MRI and plain radiography. Twenty-two patients had
      technetium bone scans, and 19 patients had Indium scans. Nineteen patients had
      all four tests performed. Patients with obvious gangrene or a fetid foot were
      excluded. RESULTS: The diagnosis of osteomyelitis was established by pathologic
      specimen (n = 18), bone culture (n = 3), or successful response to medical
      management (n = 6). Osteomyelitis was confirmed in nine of the pathologic
      specimens. The diagnostic sensitivity, specificity, and accuracy for MRI was 88%,
      100%, and 95%, respectively, for plain radiography it was 22%, 94%, and 70%,
      respectively, for technetium bone scanning it was 50%, 50%, and 50%,
      respectively, and for Indium leukocyte scanning it was 33%, 69%, and 58%,
      respectively. The data were analyzed statistically with the two-tailed Fisher's
      exact test. MRI was the only test that was statistically significant (p < 0.01).
      CONCLUSIONS: MRI appeared to be the single best test for the diagnosis of
      osteomyelitis associated with diabetic foot infections. It had a better
      diagnostic accuracy than conventional modalities and appeared to be more cost
      effective than the frequently used Indium scan.

PMID- 8752039
TI  - Survival after aberrant right subclavian artery-esophageal fistula: case report
      and literature review.
AB  - Development of a fistula between an aberrant right subclavian artery and the
      esophagus is a rare cause of heretofore fatal hematemesis. We report the first
      known survivor of this devastating complication of the most common aortic arch
      anomaly. Intraoperative esophagogastroduodenoscopy, intraesophageal balloon
      tamponade, and arteriography were the keys to successful management. This lesion
      should be suspected in the setting of bright red, "arterial" hematemesis.
      Prolonged nasogastric and/or endotracheal intubation should be avoided in
      patients with a known aberrant right subclavian artery or other aortic arch
      anomaly.

PMID- 8752040
TI  - True infrapopliteal artery aneurysms: report of two cases and literature review.
AB  - Aneurysms of the infrapopliteal arteries are rare and commonly associated with
      trauma. Most appear as false aneurysms. Because they are quite rare events, we
      describe for the first time in the English-language literature two cases of a
      combination of true aneurysms of the popliteal and tibial arteries. Symptoms at
      initial examination are calf mass and distal ischemia. Clinical features,
      radiographic findings, surgical management, and a review of the literature on
      true infrapopliteal aneurysms are discussed.

PMID- 8752042
TI  - Spontaneous rupture of left external iliac vein: case report and review of the
      literature.
AB  - Iliac vein rupture is rare and primarily results from major trauma or occurs
      during pelvic surgery. Spontaneous nontraumatic rupture is even more unusual,
      with only 14 cases reported in the literature. We report an additional case,
      summarize all of the cases, and discuss the possible causes and treatment of
      iliac vein rupture and the role of anticoagulants in postoperative management.

PMID- 8752041
TI  - Percutaneous treatment of acute iliac artery injury after intraaortic balloon
      counterpulsation.
AB  - We report on a novel approach to correcting iliac artery occlusions caused by
      aortic counterpulsation. Two patients who had leg ischemia after retrieval of an
      intraaortic balloon pump underwent angiograms that showed occlusion of the right
      external iliac artery because of dissection (one case) or thrombosis (one case).
      Percutaneous self-expandable stents were implanted in the occluded vessels, and
      they fully restored normal iliac patency with no complications and satisfactory
      midterm follow-up results. We conclude that iliac artery occlusion induced by
      aortic counterpulsation can be safely treated by implanting self-expandable
      stents in cases of acute iatrogenic dissection.

PMID- 8752044
TI  - Vision of relevant technologic progress for the next two decades.

PMID- 8752043
TI  - Congenital factor VII deficiency in a patient with an abdominal aortic aneurysm.
AB  - A patient with congenital factor VII deficiency underwent surgery for an
      inflammatory abdominal aortic aneurysm. No references in the literature have been
      found on the management of this coagulation defect in patients who require
      vascular surgery. We present one such case, with special reference to the
      perioperative management of factor VII replacement therapy.

PMID- 8752045
TI  - Medical control of abdominal aortic aneurysm expansion rate.

PMID- 8752046
TI  - Regarding "percutaneous transluminal angioplasty for emboligenic arterial lesions
      after radiotherapy of axillary arteries".

PMID- 8752047
TI  - Regarding "should percutaneous transluminal angioplasty be recommended for
      treatment of infrageniculate popliteal artery or tibioperoneal trunk stenosis?".

PMID- 8752049
TI  - Regarding "complications of peripheral arteriography".

PMID- 8752048
TI  - Angioembolization of multiple intrasplenic pseudoaneurysms as a result of blunt
      trauma.

PMID- 8752050
TI  - A new carotid clamp that facilitates distal internal carotid exposure.

PMID- 8752051
TI  - Progressive enlargement of a Miller vein cuff.

PMID- 8752052
TI  - Regarding "laparoscopic vascular surgery: four case reports".

PMID- 8752054
TI  - Can Canada afford type of care afforded to MP?

PMID- 8752055
TI  - Can Canada afford type of care afforded to MP?

PMID- 8752053
TI  - Endovascular repair of subclavian artery aneurysm.

PMID- 8752056
TI  - Physicians pay for health-card fraud.

PMID- 8752057
TI  - Choose better device to treat asthma and put on a happy face.

PMID- 8752058
TI  - Clinical significance of pravastatin study results.

PMID- 8752059
TI  - Heart-rending case in Britain ends in girl's death.

PMID- 8752060
TI  - Appropriate scrutiny of excimer-laser eye surgery.

PMID- 8752061
TI  - Neurologic injury after vaccination in buttocks.

PMID- 8752062
TI  - Prevention. How much harm? How much benefit? 4. The ethics of informed consent
      for preventive screening programs.
AB  - Preventive interventions may have few or unproven benefits, or they may even be
      harmful. Since three of the fundamental precepts of Western biomedical ethics are
      beneficence, non-maleficence and respect for individual autonomy, failure to
      obtain truly informed consent for many current preventive interventions may be
      unethical. However, there are many impediments to obtaining such consent.
      Physicians need to be aware of an immense amount of up-to-date, complex
      information. It may be difficult for patients to assimilate this information, and
      there is rarely time for physicians to become informed and to inform their
      patients. Clinical practice guidelines may be helpful, but not all are based on
      evidence, and recommendations are often conflicting. Medical institutions, as
      well as individual clinicians, can help solve these dilemmas. Authors and journal
      editors can make a commitment to report and publish well-referenced evidence
      based guidelines. Organizations such as the Canadian Task Force on the Periodic
      Health Examination and the US Preventive Services Task Force can develop
      balanced, evidence-based patient-information material. Faculty at all levels of
      medical education can increase their emphasis on the ethics of prevention.
      Individual clinicians should avoid making clinical decisions on the basis of
      relative reductions of morbidity or mortality, should use evidence-based clinical
      practice guidelines rather than those based on authority whenever possible,
      should make use of patient-information material and, most important, should have
      a consistent policy of obtaining informed consent from patients before they
      participate in potentially harmful preventive programs.

PMID- 8752063
TI  - Bioethics for clinicians: 2. Disclosure.
AB  - In the context of patient consent, "disclosure" refers to the provision of
      relevant information by the clinician and its comprehension by the patient. Both
      elements are necessary for valid consent. Disclosure should inform the patient
      adequately about the treatment and its expected effects, relevant alternative
      options and their benefits and risks, and the consequences of declining or
      delaying treatment. The clinician's goal is to disclose information that a
      reasonable person in the patient's position would need in order to make an
      informed decision. Therefore, clinicians may need to consider how the proposed
      treatment (and other options) might affect the patient's employment, finances,
      family life and other personal concerns. Clinicians may also need to be sensitive
      to cultural and religious beliefs that can affect disclosure.

PMID- 8752064
TI  - How many general surgeons do you need in rural areas? Three approaches to
      physician resource planning in southern Manitoba.
AB  - OBJECTIVE: To assess critically the results of using three different approaches
      to planning for the number of general surgeons in rural areas. DESIGN: Estimates
      of the number of general surgeons needed using a ratio approach, a and a
      population-needs-based approach. SETTING: Rural southern Manitoba. OUTCOME
      MEASURE: Number of general surgeons needed. RESULTS: The ratio approach supported
      the recruitment of 7.8 to 14.5 additional general surgeons to rural southern
      Manitoba. The repatriation approach suggested that the area might support five
      additional general surgeons, if residents could be persuaded to undergo their
      surgery closer to home. The population-needs-based approach suggested that the
      health status of area residents was similar to that of residents of other areas
      of the province and that they had a higher rate of surgery than residents of
      other areas; no additional surgeons were apparently needed. CONCLUSIONS: Each
      method has certain advantages, and none is necessarily useful in isolation.
      Hence, the most effective approach to planning for general surgeons is likely a
      combination of all three methods. Other factors that may be important include the
      type of payment structure and the need for professional groups to monitor
      variations in rates of surgery.

PMID- 8752065
TI  - The alluring myth of private medicine.
AB  - Canada's medicare system has provided Canadians with high-quality health care for
      almost three decades. Now Canadian health care appears to be at risk of losing
      the single-payer system, which is the premise on which medicare is built. As
      medicare comes under increasing financial pressure, many are calling for the
      introduction of private care as a means of bolstering our health care system and
      maintaining its quality. Although it appears alluring to some politicians,
      physicians and commentators, privatization could very well lead to the demise of
      the principles and practices of the Canadian health care system as we know it,
      with little clear benefit to the public or physicians.

PMID- 8752066
TI  - The benefits of privatization.
AB  - The promise of a universal, comprehensive, publicly funded system of medical care
      that was the foundation of the Medical Care Act passed in 1966 is no longer
      possible. Massive government debt, increasing health care costs, a growing and
      aging population and advances in technology have challenged the system, which can
      no longer meet the expectations of the public or of the health care professions.
      A parallel, private system, funded by a not-for-profit, regulated system of
      insurance coverage affordable for all wage-earners, would relieve the
      overstressed public system without decreasing the quality of care in that system.
      Critics of a parallel, private system, who base their arguments on the politics
      of fear and envy, charge that such a private system would "Americanize" Canadian
      health care and that the wealthy would be able to buy better, faster care than
      the rest of the population. But this has not happened in the parallel public and
      private health care systems in other Western countries or in the public and
      private education system in Canada. Wealthy Canadians can already buy medical
      care in the United States, where they spend $1 billion each year, an amount that
      represents a loss to Canada of 10,000 health care jobs. Parallel-system schemes
      in other countries have proven that people are driven to a private system by
      dissatisfaction with the quality of service, which is already suffering in
      Canada. Denial of choice is unacceptable to many people, particularly since the
      terms and conditions under which Canadians originally decided to forgo choice in
      medical care no longer apply.

PMID- 8752067
TI  - Zoonotic diseases in Canada: an interdisciplinary challenge.
AB  - Although zoonotic diseases are generally rare in Canada, a wide range of
      pathogens can be transmitted from animal reservoirs to humans through insect
      vectors or direct contact with wild and domestic animals. Across the country
      researchers with backgrounds ranging from wildlife biology to parasitology and
      epidemiology are tracking a variety of zoonotic diseases, some of which are
      causing increasing concern among public health officials.

PMID- 8752068
TI  - New draft code for research involving humans proved a major challenge.
AB  - A new draft code of conduct for research involving humans aims to bring a fresh
      vision to the ethics field. The code is a joint endeavour of the Medical Research
      Council, the Natural Sciences and Engineering Research Council and the Social
      Sciences and Humanities Research Council and supersedes all three agencies'
      earlier ethics statements. Once the draft code is revised and approved, likely by
      the end of the year, investigators will have a more refined understanding of the
      ethical limits of acceptable research.

PMID- 8752069
TI  - The Jenkins of Charlottetown.
AB  - For nearly a century residents of Prince Edward Island were served by three
      physicians known collectively to the community as Dr. Jenkins. Father John, son
      Stephen and grandson Jack, each of whom won acclaim for service to medicine, war
      service and political work, practised a total of 89 years, from 1856 to 1945.
      This article looks back at a distinguished family's career in medicine.

PMID- 8752070
TI  - Physicians and the minefield surrounding informed consent.
AB  - Most of the legal cases that follow the informed-consent standard set in recent
      court cases have involved surgical procedures. However, issues concerning a
      pregnant British Columbia mother who contracted chicken pox and whose child was
      subsequently born with severe medical complications demonstrate the complexity of
      medical decision making and the inadequacy of established legal requirements,
      especially when consent has dimensions beyond technical considerations usually
      associated with medical procedures. The problem physicians face, says lawyer
      Karen Capen, is to find a way to balance a range of professional responsibilities
      and the overriding fiduciary obligation to patients in matters associated with
      informed decision making and consent.

PMID- 8752071
TI  - Eye bank's success due to vision of its founders.
AB  - In 1955, the Eye Bank of Canada introduced Canadians to the idea of postmortem
      tissue donation. The long-time administrator of the bank's Ontario Division, Anne
      Wolf, recalls the organization's early days and how the management of donated
      corneas became a family affair.

PMID- 8752072
TI  - Education, practice reviews needed to reduce surgical intervention, Quebec report
      says.
AB  - Clinical uncertainty may be the reason for large variations in the rates of
      tonsillectomy, adenoidectomy and myringotomy in Quebec, a report prepared for the
      provincial government states. Methods used in other jurisdictions, such as
      informing physicians about geographic differences in intervention rates and
      developing clinical practice guidelines, could reduce the variations and save
      millions of dollars, researchers suggest.

PMID- 8752073
TI  - Cross-cultural perspectives on menopause.
AB  - Numerous physical and psychological symptoms have been attributed to the hormonal
      changes of menopause. Symptoms have also been attributed to loss of fertility,
      redefining of roles, empty nest syndrome, loss of femininity, and changes of
      status. Cross-cultural studies allow researchers to examine the contribution of
      physiological, psychological, and sociocultural influences to the experience of
      menopausal symptoms. Such research is complicated by differences between cultures
      in the definition of menopause, reproductive histories, symptom expression, and
      beliefs as to what constitutes status. A review of five important cross-cultural
      studies indicates that there are enormous differences in the experience of
      menopause among women in the same culture and among cultures. Menopausal symptoms
      seem to be caused by a combination of physical changes, cultural influences, and
      individual perceptions and expectations.

PMID- 8752074
TI  - Long-term persisting cognitive sequelae of traumatic brain injury and the effect
      of age.
AB  - This study examined the notion that mild to moderate traumatic brain injury (TBI)
      may have persistent effects that become evident upon neurocognitive testing in a
      phase in which the effects of physiological aging become manifest. Neurocognitive
      performance was tested in 25 middle-aged and 20 old subjects who had sustained
      mild to moderate TBI, on average, several decades earlier. The TBI subjects
      regarded themselves as normal and healthy. The performance of the TBI subjects
      was inferior to that of matched healthy controls on all aspects of primary and
      secondary memory and on the majority of tests used to measure speed of
      performance. There was no interaction between the effects of TBI and those of
      age, and the performance of middle-aged TBI subjects was similar to that of old
      controls. The results are taken to indicate that TBI sustained earlier in life
      may cause permanent sequelae in specific domains of cognitive functioning and
      that it might attenuate the age-related decline in cognitive functioning. Most
      striking, however, was that these deficits were not perceived as a limiting
      factor in everyday life, which suggests that coping strategies may be important.

PMID- 8752075
TI  - The case for a dissociative interpretation of pseudoepileptic seizures.
AB  - A pseudoepileptic seizure (PES) can be considered as a paroxysmal behavior
      pattern that mimics epilepsy and is initiated by psychological mechanisms. There
      is no evidence that the symptomatology of PES forms a specific syndrome. This
      paper presents evidence for the explanatory value of the concept of dissociation
      in at least a subgroup of PES. Characteristics of patients with PES and possible
      factors in the etiology of PES are reviewed. Based on the dissociation
      hypothesis, some suggestions are offered to explain the relatively high
      comorbidity of PES and epilepsy.

PMID- 8752076
TI  - Life domains, alcoholics anonymous, and role incumbency in the 3-year course of
      problem drinking.
AB  - This study examined the course of problem drinking among 439 individuals over 3
      years, using a life domains perspective that distinguishes life stressors and
      social resources in different contexts. More severe chronic financial stressors
      both predicted and were predicted by more alcohol consumption and drinking
      related problems. Among social resources, Alcoholics Anonymous was the most
      robust predictor of better functioning on multiple outcome criteria. Support from
      friends and extended family also predicted better outcomes; this effect was
      stronger for individuals who were low on primary role incumbency (i.e., who were
      unemployed and/or did not have a spouse/partner).

PMID- 8752077
TI  - Planned versus actual duration of drug abuse treatment. Reconciling observational
      and experimental evidence.
AB  - The purpose of the study was to evaluate the associations of planned versus
      actual duration of drug abuse treatment with psychosocial outcomes and drug use
      at follow-up. A randomized trial was conducted in a modified therapeutic
      community in which 444 clients were assigned to programs with planned durations
      of either 3 or 6 months. Outcomes were psychosocial measures assessing changes in
      mood and in stage of behavior change between admission and exit and return to
      drug use and patterns of use 2 to 6 months after exit. Planned duration was not
      associated with any of the outcomes. A longer actual length of stay was, however,
      associated with greater improvements in the mood variables; lower rates of drug
      use at follow-up; and, among those using drugs at follow-up, a longer time from
      exit to first drug use. Intention-to-treat analyses supported these results.
      Randomized controlled trials are needed to distinguish the effects of planned
      duration and actual length of stay.

PMID- 8752078
TI  - The relationship between parental communication deviance and relapse in
      schizophrenic patients in the 1-year period after hospital discharge. A pilot
      study.
AB  - The present pilot study examined the ability of parental communication deviance
      (CD) to predict relapse in schizophrenic patients in the 1-year period after
      hospital discharge. Measures of CD were obtained from verbatim transcripts of
      family problem-solving discussions for 20 schizophrenic patients and their
      parents at an initial assessment and before the patients' hospital discharge.
      Relapse was assessed using the Brief Psychiatric Rating Scale at 3-month
      intervals after discharge. Findings indicated that parental CD measured at an
      assessment immediately before the patient's release from the hospital was
      moderately correlated (r = .49, p < .05) with relapse in the 1-year follow-up
      period. Results are discussed with respect to the possible role of parental CD as
      an environmental stressor in the period after discharge. Potential contributors
      to parental CD, including genetically transmitted cognitive deficits and stress
      resulting from resuming the care-giver role, are also discussed.

PMID- 8752079
TI  - Major depressive disorder in Taiwan defined by the Chinese diagnostic Interview
      Schedule.
AB  - The lifetime prevalence rate of major depressive disorder (MDD), as defined by
      the Chinese Diagnostic Interview Schedule, is 1.14% in Taiwan. This is
      significantly lower than the lifetime prevalence rates reported in Western
      studies and similar to other studies in the Chinese population using similar
      methods for assessing cases of MDD. Epidemiological data from 136 MDD cases were
      analyzed to provide possible explanations for this difference in lifetime
      prevalence rates. The low rate of broken families in Chinese culture, low
      comorbidity rate, and older age of onset of MDD may suggest a reality of low
      lifetime prevalence rates of MDD in Taiwan.

PMID- 8752080
TI  - A preliminary study of the relationship among personality, cognitive
      vulnerability, symptom profile, and outcome in major depressive disorder.

PMID- 8752081
TI  - Written disclosure in posttraumatic stress disorder: is it beneficial for the
      patient?

PMID- 8752082
TI  - The efficacy of short-term treatment for improving quality of life: a pilot
      study.

PMID- 8752083
TI  - Psychosocial factors and chronic depression.

PMID- 8752084
TI  - Direct analysis of nematode cis- and trans-spliceosomes: a functional role for U5
      snRNA in spliced leader addition trans-splicing and the identification of novel
      Sm snRNPs.
AB  - Most nuclear pre-mRNAs in nematodes are processed by both cis- and trans
      splicing. In trans-splicing, the 5' terminal exon, the spliced leader sequence
      (SL), is derived from a trans-splicing specific Sm snRNP, the SL RNP. Because U
      snRNPs are required cofactors for trans-splicing, and because this processing
      reaction proceeds via a two-step reaction pathway identical to that of cis
      splicing, it has long been assumed that trans-splicing is catalyzed in a complex
      analogous to the cis-spliceosome. However, similarities or differences between
      cis- and trans-spliceosomes have not been established. In particular, the role of
      U5 snRNP in trans-splicing has been unclear. Here, we have used affinity
      selection to analyze the U snRNA constituents of nematode cis- and trans
      spliceosomes. We find that U5 snRNP is an integral component of the trans
      spliceosome and, using site-specific crosslinking, we show that U5 snRNP
      establishes specific Interactions with the SL RNA exon. We also identify two
      novel Sm snRNPs that are enriched in both cis- and trans-spliceosomes. Finally,
      we provide evidence that a SL RNP-containing multi-snRNP (SL, U4, U5, and U6
      RNPs) may be a functional precursor in trans-spliceosome assembly.

PMID- 8752085
TI  - Multiple requirements for nematode spliced leader RNP function in trans-splicing.
AB  - The 5' exon donor in nematode trans-splicing, the SL RNA, is a small
      (approximately 100 nt) RNA that resembles cis-spliceosomal U snRNAs. Extensive
      analyses of the RNA sequence requirements for SL RNA function have revealed four
      essential elements, the core Sm binding site, three nucleotides immediately
      downstream of this site, a region of Stem-loop II, and a 5' splice site. Although
      these elements are necessary and sufficient for SL RNA function in vitro, their
      respective roles in promoting SL RNA activity have not been elucidated.
      Furthermore, although it has been shown that assembly of the SL RNA into an Sm
      RNP is a prerequisite for function, the protein composition of the SL RNP has not
      been determined. Here, we have used oligoribonucleotide affinity to purify the SL
      RNP and find that it contains core Sm proteins as well as four specific proteins
      (175, 40, 30, and 28 kDa). Using in vitro assembly assays; we show that
      association of the 175- and 30-kDa SL-specific proteins correlates with SL RNP
      function in trans-splicing. Binding of these proteins depends upon the sequence
      of the core Sm binding site; SL RNAs containing the U1 snRNA Sm binding site
      assemble into Sm RNPs that contain core, but not SL-specific proteins.
      Furthermore, mutational and thiophosphate interference approaches reveal that
      both the primary nucleotide sequence and a specific phosphate oxygen within a
      segment of Stemloop II of the SL RNA are required for function. Finally,
      mutational activation of an unusual cryptic 5' splice site within the SL sequence
      itself suggests that U5 snRNA may play a primary role in selecting and specifying
      the 5' splice site in SL addition trans-splicing.

PMID- 8752086
TI  - The ion-induced folding of the hammerhead ribozyme: core sequence changes that
      perturb folding into the active conformation.
AB  - The hammerhead ribozyme undergoes an ion-dependent folding process into the
      active conformation. We find that the folding can be blocked at specific stages
      by changes of sequence or functionality within the core. In the the absence of
      added metal ions, the global structure of the hammerhead is extended, with a
      large angle subtended between stems I and II. No core sequence changes appear to
      alter this geometry, consistent with an unstructured core under these conditions.
      Upon addition of low concentrations of magnesium ions, the hammerhead folds by an
      association of stems II and III, to include a large angle between them. This
      stage is inhibited or altered by mutations within the oligopurine sequence lying
      between stems II and III, and folding is completely prevented by an A14G
      mutation. Further increase in magnesium ion concentration brings about a second
      stage of folding in the natural sequence hammerhead, involving a reorientation of
      stem I, which rotates around into the same direction of stem II. Because this
      transition occurs over the same range of magnesium ion concentration over which
      the hammerhead ribozyme becomes active, it is likely that the final conformation
      is most closely related to the active form of the structure. Magnesium ion
      dependent folding into this conformation is prevented by changes at G5, notably
      removal of the 2'-hydroxyl group and replacement of the base by cytidine. The
      ability to dissect the folding process by means of sequence changes suggests that
      two separate ion-dependent stages are involved in the folding of the hammerhead
      ribozyme into the active conformation.

PMID- 8752087
TI  - A misfolded form of 5S rRNA is complexed with the Ro and La autoantigens.
AB  - In both vertebrate and invertebrate cells, the 60-kDa Ro autoantigen is bound to
      small cytoplasmic RNAs known as Y RNAs. In Xenopus oocytes, the 60-kDa Ro protein
      is also complexed with a class of 5S rRNA precursors that contain internal
      mutations. Because these 5S rRNA precursors are processed inefficiently and
      degraded eventually, the Ro protein may function in a quality control pathway for
      5S rRNA biosynthesis. We have investigated the sequence and secondary structure
      determinants in the mutant 5S rRNAs that confer binding by the 60-kDa Ro protein.
      The mutant 5S rRNAs fold to form an alternative helix that is required for
      recognition by the 60-kDa Ro protein. Mutations that disrupt the alternative
      helix eliminate Ro protein binding, whereas compensatory changes that restore the
      helix are bound efficiently by the Ro protein. When the structure of the mutant
      RNA was probed using dimethylsulfate and oligonucleotide-directed RNase H
      cleavage, the results were consistent with the formation of the alternative
      structure. The La protein, which is also complexed with the mutant 5S rRNA
      precursors, protects similar sequences from nuclease digestion as does the 60-kDa
      Ro protein. Thus, the binding sites for these two proteins are either nearby on
      the RNA, or the two proteins may be complexed through protein-protein
      interactions. When the human Ro protein is expressed in the yeast Saccharomyces
      cerevisiae, the protein binds wild-type 5S rRNA precursors, suggesting that a
      population of wild-type precursors also folds into the alternative structure.

PMID- 8752088
TI  - Small RNA-divalent domains.
AB  - From a potentially completely sampled set of randomized 23-mer sequences, we
      selected RNAs that bind a Zn-column and also show KD approximately 100-400 microM
      for free Zn2+, probably relying on one or two direct ion coordinations.
      Comparison of selected sequences with previously known divalent sites suggests
      three or four small RNA motifs repeatedly found to interact with divalent ions.
      We suggest that the GC cluster, the augmented GC cluster, and the E element may
      be useful generalized ion-binding structures. Such structures may help identify
      similar divalent sites in sequenced RNAs and serve as substructures for design of
      functional RNA metallodomains.

PMID- 8752089
TI  - Mammalian splicing factor SF1 is encoded by variant cDNAs and binds to RNA.
AB  - Mammalian splicing factor SF1 consists of a single polypeptide of 75 kDa and is
      required for the formation of the first ATP-dependent spliceosomal complex. Three
      cDNAs encoding variant forms of SF1 have been isolated and four highly related
      cDNAs have been found in current databases. Comparison of the cDNA sequences
      suggests that different SF1 mRNAs are generated by alternative splicing of a
      common pre-mRNA. In agreement with this idea, at least three mRNAs that are
      differentially expressed in different cell types have been detected by northern
      blot analysis. All SF1 cDNAs identified encode proteins with a common N-terminal
      half that contains two structural motifs implicated in RNA binding (an hnRNP K
      homology [KH] domain and a zinc knuckle), but the proteins differ in the length
      of a proline-rich region and have distinct C-termini. Three SF1 isoforms
      expressed in insect cells via baculovirus transfer vectors show comparable
      activities in the assembly of a pre-splicing complex. Consistent with the
      presence of a KH domain and a zinc knuckle, we show that SF1 binds directly to
      RNA. This interaction appears to be largely sequence-independent with a
      preference for guanosine- and uridine-rich sequences. The KH domain of SF1 is
      embedded in a 160-amino acid sequence that is shared with human Sam68, a target
      of Src during mitosis, as well as Caenorhabditis elegans GLD-1 and mouse Qkl,
      both of which play roles during cellular differentiation. The presence of this
      shared region in SF1 suggests functions in addition to its role in pre
      spliceosome assembly.

PMID- 8752090
TI  - The Sm binding site targets U7 snRNA to coiled bodies (spheres) of amphibian
      oocytes.
AB  - Using cytoplasmic and nuclear injection assays, we show that U7 snRNA constructs
      are targeted rapidly and specifically to the coiled bodies (spheres) in the
      germinal vesicle (GV) of the amphibian oocyte, including those coiled bodies
      attached to the lampbrush chromosomes at the histone gene loci. Because the U7
      snRNP is required for removing the 3' end of histone pre-mRNA, we suggest that a
      major function of coiled bodies is to recruit U7 snRNPs to the histone gene loci,
      before they associate with the pre-mRNA. Targeting to coiled bodies requires the
      specific U7 Sm binding site; replacement of the U7 Sm site by that of U2 snRNA
      reduces this targeting dramatically. No other part of the molecule is required,
      and the U7 Sm binding site alone is sufficient to direct nuclear import of an
      unrelated RNA sequence and its specific targeting to coiled bodies. Injected U7
      constructs displace the endogenous U7 in the coiled bodies, the amount of
      injected U7 that ends up in coiled bodies being roughly equal to the amount of
      endogenous U7 snRNA.

PMID- 8752091
TI  - Identification of cis-acting signals in the giardiavirus (GLV) genome required
      for expression of firefly luciferase in Giardia lamblia.
AB  - Giardiavirus (GLV) is a 6,277-bp double-stranded RNA virus of Giardia lamblia,
      one of the earliest eukaryotic divergents from the prokaryotes. Our previous
      success in GLV-mediated transfection of G. lamblia has provided an effective way
      of monitoring the mechanisms underlining GLV gene replication and mRNA
      translation in this organism. Here we have investigated the cis-acting signals in
      the GLV genome that regulate replication, transcription, and translation of an
      inserted firefly luciferase gene in GLV-infected G. lamblia. By modifying the two
      terminal regions of a full-length GLV cDNA clone used to flank a luciferase gene,
      various in vitro chimeric transcripts were generated and introduced into GLV
      infected G. lamblia via electroporation. Expression of luciferase (+) strand and
      (-) strand RNAs in the transfected cells was monitored and the luciferase
      activity assayed. The results indicated that the 5'-untranslated region (UTR) of
      366 nt and the 3'-terminal 2,022 nt of the viral transcript are both needed for
      optimal expression of the two RNA strands. Although the entire 5'-UTR is needed
      for the chimeric mRNA synthesis, both the primary sequence and the secondary
      structure at the 3' end of GLV transcript are essential for the synthesis of (-)
      strand RNA. When the 5' end of GLV transcript was extended 265 nt into the capsid
      protein open reading frame and fused with that of luciferase, there was no change
      in the level of luciferase chimeric RNA, but a 5,000-fold increase of luciferase
      activity was observed that may be attributed to an enhanced translational
      efficiency of the chimeric mRNA in G. lamblia.

PMID- 8752092
TI  - Identification and characterization of yeast mutants that overcome an
      experimentally introduced block to splicing at the 3' splice site.
AB  - An experimentally introduced secondary structure in exon 2 adjacent to the 3'
      splice site of a yeast ACT-Escherichia coli lacZ fusion gene abolishes splicing
      in vivo and inhibits beta-galactosidase production. We have devised a genetic
      screen to isolate both cis and trans-acting mutants that restore beta
      galactosidase activity. Two cis-acting mutants potentially destabilize the stem
      in the region close to the 3' splice site. One trans-acting mutant, designated
      rss1-1, partially restores beta-galactosidase activity by both increasing the
      splicing efficiency and stabilizing the precursor and lariat intermediate. The
      trans-acting suppression activity of rss1-1 is specific for a particular
      structure because another artificially introduced secondary structure, which also
      blocks splicing, is not suppressed by this mutant allele. We have cloned the gene
      encoding the trans-acting mutant protein. The RSS1 gene is located on
      Saccharomyces cerevisiae chromosome V and is a single copy, essential gene. The
      predicted RSS1 protein has marked similarity to members of the putative ATP
      dependent RNA helicase family. At the nonpermissive temperature, the rss1-1
      mutant allele decreases the steady-state levels of several endogenous messenger
      RNAs and increases the ratio of pre-mRNA to mRNA of specific messages. RSS1 is
      likely to play an interesting role in RNA processing.

PMID- 8752093
TI  - Role of proteoglycans in neural development, regeneration, and the aging brain.

PMID- 8752094
TI  - Tryptophan hydroxylase: cloning and expression of the rat brain enzyme in
      mammalian cells.
AB  - A cDNA encoding full-length tryptophan hydroxylase was produced by reverse
      transcriptase-PCR from rat brain mRNA and expressed transiently in a human
      fibroblast cell line. Catalytic activity was low unless transfected cells were
      grown in the presence of FeSO4. Recombinant tryptophan hydroxylase was found
      almost exclusively within the soluble compartment of the cell and was dependent
      on tryptophan and tetrahydrobiopterin for activity. The catalytic activity of
      recombinant tryptophan hydroxylase was stimulated > 25-fold by Fe(II) and to a
      somewhat lesser extent by the polyanions heparin and phosphatidylserine. The
      enzyme was inhibited by desferrioxamine and dopamine, both of which complex iron.
      When extracts from transfected cells were subjected to sucrose gradient
      centrifugation and analytical gel filtration, the recombinant enzyme behaved the
      same as the native enzyme from brain. A monoclonal antibody against phenylalanine
      hydroxylase that cross-reacts with brain tryptophan hydroxylase was capable of
      immunoprecipitating the recombinant hydroxylase from solution. These data
      indicate that recombinant tryptophan hydroxylase expressed in mammalian cells is
      assembled into tetramers of approximately 220,000 daltons. Its catalytic and
      physical properties appear to be very similar to those of the native enzyme from
      brain.

PMID- 8752095
TI  - Characterization of a cerebellar granule cell-specific gene encoding the gamma
      aminobutyric acid type A receptor alpha 6 subunit.
AB  - The alpha 6 subunit of gamma-aminobutyric type A receptors is a marker for
      cerebellar granule cells and is an attractive candidate to study cell-specific
      gene expression in the brain. The mouse alpha 6 subunit gene has nine exons and
      spans approximately 14 kb. The largest intron (intron 8) is approximately 7 kb.
      For a minority of mRNAs, a missplice of the first exon was identified that
      disrupts the signal peptide and most likely results in the production of
      nonfunctional protein. The gene is transcribed from a TATA-less promoter that
      uses multiple start sites. Using transgenic mice, it was found that the proximal
      0.5 kb of the rat alpha 6 gene upstream region confers expression on a beta
      galactosidase reporter gene. One founder gave rise to a line with cerebellar
      granule cell-specific expression, although expression varied with lobule region.
      Other founders had ectopic but neuron-specific expression, with beta
      galactosidase found in cerebellar Purkinje cells, neocortex, thalamus,
      hippocampus, caudate-putamen, and inferior colliculi. Thus, we have defined a
      region containing the basal promoter of the alpha 6 subunit gene and that confers
      neuron-specific expression.

PMID- 8752096
TI  - Expression and deletion mutagenesis of tryptophan hydroxylase fusion proteins:
      delineation of the enzyme catalytic core.
AB  - cDNAs encoding the full-length sequence for tryptophan hydroxylase, and deletion
      mutants consisting of the regulatory (amino acids 1-98) or catalytic (amino acids
      99-444) domains of the enzyme, were cloned and expressed as glutathione S
      transferase fusion proteins in E. coli. The recombinant fusion proteins could be
      purified to near homogeneity within minutes by affinity chromatography on
      glutathione-agarose. The full-length enzyme and the catalytic core expressed very
      high levels of tryptophan hydroxylase activity. The regulatory domain was devoid
      of activity. The full-length enzyme and the catalytic core, while adsorbed to
      glutathione-agarose beads, obeyed Michaelis-Menten kinetics, and the kinetic
      properties of each recombinant enzyme for cofactor and substrate compared very
      closely to native, brain tryptophan hydroxylase. Both active forms of the
      glutathione S-transferase-tryptophan hydroxylase fusion proteins had strict
      requirements for ferrous iron in catalysis and expressed much higher levels of
      activity (Vmax) than the brain enzyme. Analysis of full-length tryptophan
      hydroxylase and the catalytic core by molecular sieve chromatography under
      nondenaturing conditions revealed that each fusion protein behaved as a
      tetrameric species. These results indicate that a truncated tryptophan
      hydroxylase, consisting of amino acids 99-444 of the full-length enzyme, contains
      the sequence motifs needed for subunit assembly. Both wild-type tryptophan
      hydroxylase and the catalytic core are expressed as apoenzymes which are
      converted to holoenzymes by exogenous iron. The tryptophan hydroxylase catalytic
      core is also as active as the full-length enzyme, suggesting the possibility that
      the regulatory domain exerts a suppressive effect on the catalytic core of
      tryptophan hydroxylase.

PMID- 8752097
TI  - Three dynamin-encoding genes are differentially expressed in developing rat
      brain.
AB  - Dynamin proteins are members of a recently described family of GTPases involved
      in receptor-mediated processes. To date, three different dynamin-encoding genes
      have been identified in mammalian tissues. Dynamin I is expressed only in
      neurons, whereas dynamin II is ubiquitously expressed. A third isoform, dynamin
      III, was originally isolated from a rat testis cDNA library and shown to be
      testis-specific. However, here we report the cloning and characterization of
      dynamin III from brain and lung, demonstrating a more extended pattern of
      expression for this isoform. In addition, we have investigated the temporal
      pattern of expression of these three genes during brain development. We find that
      both dynamin I and dynamin III mRNA levels are up-regulated during embryogenesis,
      whereas dynamin II mRNA levels remain unchanged. From these results, we conclude
      that dynamin III is not a testis-specific isoform and, furthermore, that rat
      brain expresses three different dynamin-encoding genes that are differentially
      regulated during development. Therefore, this large isoform diversity of dynamin
      proteins in brain predicts a significant complexity in the understanding of
      dynamin-based processes in this tissue.

PMID- 8752098
TI  - Cloning and characterization of aplycalcin and Aplysia neurocalcin, two new
      members of the calmodulin superfamily of small calcium-binding proteins.
AB  - We report here the sequences of two new proteins from Aplysia, aplycalcin and
      Aplysia neurocalcin. These proteins belong to a family of calcium-binding
      proteins, found primarily in vertebrate brain and retina, that have been proposed
      to play a role in calcium-dependent regulation of enzymes in signal transduction
      pathways. Like other members of this family, the Aplysia proteins have consensus
      sequences for myristoylation, bind calcium, and translocate from cytosol to
      membrane when the calcium level is raised above the resting intracellular
      concentration. Both proteins are relatively enriched in Aplysia nervous system,
      but are also found to a significant degree in other tissues. The expression of
      mRNA for these proteins in Aplysia nervous tissue is regulated during
      development, roughly paralleling the reported emergence of several forms of
      synaptic plasticity. The messages are present at low levels in stage 11, show a
      large increase by late stage 12, and decline to a plateau of approximately 30% of
      the peak value afterward. On the basis of the properties of these proteins and by
      analogy with proposed functions of some of the retinal homologues, we suggest
      that these proteins may play a role in mediating calcium-dependent processes in
      neuronal function. The presence of both proteins in other tissues may suggest
      analogous roles for the proteins in other cell types.

PMID- 8752099
TI  - 2',3'-Cyclic nucleotide 3'-phosphodiesterase binds to actin-based cytoskeletal
      elements in an isoprenylation-independent manner.
AB  - 2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNP) is an isoprenylated protein
      enriched in myelin and oligodendrocytes but also present in several other tissues
      at low levels. CNP binds avidly to membranes and in addition possesses several
      characteristics of cytoskeletal proteins. The role of isoprenylation in the
      association of CNP with the cytoskeleton was analyzed by ectopic expression in L
      cells of epitope-tagged CNP1 and a non-isoprenylated mutant CNP1. Using nonionic
      detergent extraction, drug-mediated cytoskeletal disruption, and
      coimmunoprecipitation with an anti-actin antibody, we show that CNP1 is
      associated with actin-based cytoskeletal elements independently of its
      isoprenylation status. A control protein, p21c-H-ras, which is also modified by
      isoprenylation at its carboxyl-terminus, does not bind to cytoskeletal structures
      as judged by the same criteria. We present a model that accounts for the
      association of CNP1 with membranes and the cytoskeleton.

PMID- 8752100
TI  - Neurotrophin-3 and brain-derived neurotrophic factor activate multiple signal
      transduction events but are not survival factors for hippocampal pyramidal
      neurons.
AB  - Expression of the neurotrophin-3 (NT-3) receptor (TrkC) and the effects of NT-3
      on signal transduction were investigated in highly enriched populations of
      embryonic rat hippocampal pyramidal neurons grown in bilaminar cultures. PCR
      analysis revealed that the predominant trkC isoform is K1, which lacks an insert
      in the kinase domain. Polyclonal TrkC-specific antibodies stained > 90% of the
      neurons and revealed a single approximately 145-kDa protein in immunoblots of
      extracts from adult hippocampus and pyramidal neuron cultures. Addition of NT-3
      (50 ng/ml) to these cultures induced the tyrosine phosphorylation of TrkC but not
      TrkB, as determined by anti-phosphotyrosine staining of immunoprecipitates; thus,
      all the effects of NT-3 are mediated through TrkC. NT-3 also increased the
      tyrosine phosphorylation of 42-, 44-, 49-, 55-, 95-, and 145-kDa proteins; the
      pattern induced by brain-derived neurotrophic factor (BDNF) was similar but not
      identical to that induced by NT-3, suggesting that subtle differences may exist
      in signaling by TrkB and TrkC receptors. Immunoprecipitation of p21ras from 32P
      prelabeled cells showed that NT-3 increased the level of the GTP-bound form of
      the protein threefold over the control within 5 min. Mitogen-activated protein
      (MAP) kinase activity was maximally elevated by NT-3 within 2 min and then
      returned slowly toward baseline over the next 60 min. Tyrosine phosphorylation of
      phospholipase C-gamma increased rapidly after NT-3, suggesting that this enzyme
      becomes activated. Consistent with this, the neurotrophin rapidly increased
      protein kinase C activity as well as intracellular Ca2+ levels. The effects of
      both NT-3 and BDNF on Ca2+ levels were attenuated in Ca(2+)-free medium,
      suggesting that both neurotrophins increase Ca2+ flux across the plasma membrane
      as well as release from internal stores. NT-3 also increased c-Fos expression in
      > 80% of the cells; the effect peaked at 30 min and declined to baseline by 120
      min. Despite the activation of ras-MAP kinase and phosphoinositide signaling
      pathways, neither NT-3 nor BDNF alone or in combination could sustain hippocampal
      pyramidal neurons deprived of glial support. We conclude that in this system NT-3
      and BDNF do not appear to be acting as classical "neurotrophic" factors and that
      activation of the MAP kinase pathway is insufficient for the promotion of
      neuronal survival.

PMID- 8752101
TI  - Cultured leptomeningeal cells secrete cerebrospinal fluid proteins.
AB  - To extrapolate the function of the leptomeninges, we examined the profile of the
      proteins secreted from the cultured leptomeningeal cells prepared from 1-2-day
      old rats. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis
      of the medium conditioned with the cultured cells, 20-25 differentially
      distinctive protein bands were noted. Through several chromatographic procedures
      (Sephadex G-75, Mono Q, and 7C8-300), altogether 18 proteins were purified to
      homogeneity, and the partial amino acid sequence of each protein was determined.
      Homology search revealed that the major proteins included prostaglandin-D
      synthase or beta-trace protein, insulin-like growth factor (IGF)-II, IGF-binding
      protein-2, apolipoprotein E, beta 2-microglobulin, cystatin C, transferrin,
      peptidyl-prolyl cis-trans isomerase or cyclophilin C, secreted protein acidic and
      rich in cysteine, ubiquitin, lysozyme C, extracellular superoxide dismutase, and
      collagen alpha-1 (III). Most of these proteins are known to be the major brain
      derived protein constituents of CSF and are thought to play important roles in
      certain biological events in the brain. Considering the morphological features,
      the present findings suggest the importance of the leptomeninges as an origin of
      such proteins in CSF.

PMID- 8752102
TI  - Characterization of inhibitor-sensitive and -resistant adenosine transporters in
      cultured human fetal astrocytes.
AB  - The kinetic characteristics of [3H]adenosine uptake, the extent to which
      accumulated [3H]adenosine was metabolized, the effects such metabolism had on
      measurements of apparent Michaelis-Menten kinetic values of KT and Vmax, and the
      sensitivities with which nucleoside transport inhibitors blocked [3H] adenosine
      accumulations were determined in cultured human fetal astrocytes. KT and Vmax
      values for accumulations of [3H]-labeled purines using 15-s incubations in the
      absence of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)
      adenine (EHNA) and the adenosine kinase inhibitor 5'-iodotubercidin (ITU) were
      6.2 microM and 0.15 nmol/min/mg of protein for the high-affinity and 2.6 mM and
      21 nmol/min/mg of protein for the low-affinity components, respectively. In the
      presence of EHNA and ITU, where < 4% of accumulated [3H] adenosine was
      metabolized, transport per se was measured, and kinetic values for KT and Vmax
      were 179 microM and 5.2 nmol/min/mg of protein, respectively. In the absence of
      EHNA and ITU, accumulated [3H]adenosine was rapidly metabolized to AMP, ADP, and
      ATP, and caused an appearance of "concentrative" uptake in that the intracellular
      levels of [3H]-labeled purines (adenosine plus its metabolites) were 1.4-fold
      higher than in the medium. No apparent concentrative accumulations of
      [3H]adenosine were found when assays were conducted using short incubation times
      in the absence or presence of EHNA and ITU. The nucleoside transport inhibitors
      dipyridamole (DPR), nitrobenzylthioinosine (NBI), and dilazep biphasically
      inhibited [3H]-adenosine transport; for the inhibitor-sensitive components the
      IC50 values were 0.7 nM for NBI, 1.3 nM for DPR, and 3.3 nM for dilazep, and for
      the inhibitor-resistant component the IC50 values were 2.5 microM for NBI, 5.1
      microM for dilazep, and 39.0 microM for DPR. These findings, in cultured human
      fetal astrocytes, represent the first demonstration of inhibitor-sensitive and 
      resistant adenosine transporters in nontransformed human cells.

PMID- 8752103
TI  - Physiologic levels of beta-amyloid activate phosphatidylinositol 3-kinase with
      the involvement of tyrosine phosphorylation.
AB  - The beta-amyloid protein (A beta) peptide plays an important role in Alzheimer's
      disease, but the potential actions of physiologic levels of A beta (225-625 pM)
      have not been explored. We recently showed that picomolar doses of A beta can
      stimulate tyrosine phosphorylation of neuronal cells and now show that leads to
      the activation of the lipid kinase phosphatidylinositol 3-kinase (PI3 kinase).
      Three independent lines of evidence support the hypothesis that A beta is
      activating PI3 kinase through a tyrosine kinase-mediated mechanism.
      Immunoblotting studies show that A beta induces tyrosine phosphorylation of p85
      as well as association of the p85 subunit of PI3 kinase with tyrosine
      phosphorylated proteins. Studies of membrane proteins show that A beta induces a
      translocation of p85 to membrane-bound glycoproteins, which are likely to be
      receptors. Finally, direct studies of PI3 kinase activity in both anti
      phosphotyrosine immunocomplexes and wheat germ agglutinin precipitates show that
      A beta increases formation of the product of PI3 kinase. Wortmannin, a selective
      inhibitor of PI3 kinase, blocks this A beta-stimulated PI3 kinase activity. Thus,
      physiologic levels of A beta stimulate tyrosine phosphorylation and PI3 kinase
      activity.

PMID- 8752104
TI  - Functional expression of P-glycoprotein in an immortalised cell line of rat brain
      endothelial cells, RBE4.
AB  - The presence of P-glycoprotein in the cell plasma membrane limits the penetration
      of many cytotoxic substances into cells that express the gene product. There is
      considerable evidence also to indicate that P-glycoprotein is expressed as part
      of the normal blood-brain barrier in the luminal membranes of the cerebral
      capillary endothelial cells, where it presumably performs a protective function
      for the brain. This report describes the functional expression of P-glycoprotein
      in an immortalised cell line, RBE4, derived from rat cerebral capillary
      endothelial cells. The expression of P-glycoprotein is demonstrated by western
      immunoblotting and by immunogold and fluorescent staining with monoclonal
      antibodies. The cellular accumulation of [3H]colchicine and [3H]-vinblastine is
      investigated and shown to be enhanced by the presence of azidothymidine,
      chlorpromazine, verapamil, cyclosporin A, and PSC 833 ([3'-keto-Bmt1]-[Val2]
      cyclosporin) at 50 or 100 microM concentration. It is concluded that the RBE4
      cell line is a valuable tool for investigating the mechanisms of P-glycoprotein
      activity both in the blood-brain barrier and in multidrug resistance in general.

PMID- 8752105
TI  - Angiotensin II regulation of intracellular calcium in astroglia cultured from rat
      hypothalamus and brainstem.
AB  - This study examines the angiotensin II (Ang II) regulation of intracellular free
      calcium concentration ([Ca2+]i) in astroglia cultured from the hypothalamus and
      brainstem of the adult rat. Bath perfusion or rapid puffer application of
      angiotensin II (Ang II) (1-100 nM) increased [Ca2+]i in both polygonal and
      stellate astroglia when measured using fura-2 imaging fluorescence microscopy.
      Ang II increased [Ca2+]i in 96.1 and 95.6% of the polygonal and stellate glial
      cells, respectively. In normal Tyrode's solution (containing 2 mM CaCl2), the Ang
      II-stimulated increase in [Ca2+]i characteristically showed a biphasic response,
      i.e., an initial rapid transient peak followed by a sustained, steady-state
      plateau of free Ca2+. In both cell types, the selective Ang II type 1 receptor
      subtype (AT1) antagonist losartan (1 microM) inhibited the Ang II-stimulated
      increase in [Ca2+]i. The selective AT2 antagonist PD 123319 (1 microM) did not
      inhibit the Ang II-stimulated increase in [Ca2+]i in either cell type. To define
      the sources of Ca2+ that participate in the Ang II-stimulated increase in [Ca2+]i
      in astroglia, experiments were performed in a nominally Ca(2+)-free Tyrode's
      solution. In either cell type, this resulted in only an initial transient
      increase of Ca2+ and no sustained plateau of Ca2+ when challenged with Ang II.
      Thapsigargin (5 microM), cyclopiazonic acid (10 microM), and ryanodine (10
      microM), but not caffeine (1-10 mM), inhibited the initial rise in [Ca2+]i. The
      plateau increase of [Ca2+]i caused by Ang II (100 nM) was reversibly inhibited by
      both cadmium (100 microM) and nifedipine (10 microM); in contrast, gadolinium
      (100 microM) had no effect on the plateau increase of [Ca2+]i. These results
      indicate that Ang II, in physiological concentrations, can activate AT1 receptors
      to stimulate both Ca2+ release from intracellular stores and Ca2+ influx from the
      extracellular space to increase [Ca2+]i of polygonal and stellate astroglia.

PMID- 8752106
TI  - Characterization of pituitary adenylate cyclase-activating polypeptide 38
      (PACAP38)-, PACAP27-, and vasoactive intestinal peptide-stimulated responses in
      N1E-115 neuroblastoma cells.
AB  - In this study, the effects of three related peptides, pituitary adenylate cyclase
      activating polypeptide 38 (PACAP38), PACAP27, and vasoactive intestinal peptide
      (VIP), on cyclic AMP (cAMP) accumulation and intracellular Ca2+ concentration
      ([Ca2+]i) were compared in N1E-115 cells. PACAP38 and PACAP27 stimulated cAMP
      accumulation up to 60-fold with EC50 values of 0.54 and 0.067 nM, respectively.
      The effect of VIP on cAMP accumulation was less potent. The binding of 125I
      PACAP27 to intact cells was inhibited by PACAP38 and PACAP27 (IC50 values of 0.44
      and 0.55 nM, respectively) but not by VIP. In fura-2-loaded cells, both PACAP38
      and PACAP27 increased [Ca2+]i with EC50 values around 10 nM. The interactions of
      these three peptides with ionomycin, a Ca2+ ionophore, and 4 beta-phorbol 12
      myristate 13-acetate (PMA), an activator of protein kinase C, were also
      determined. Ionomycin increased the cAMP accumulation caused by all three
      peptides. With low concentrations of PACAP38 or PACAP27, the effect of PMA was
      inhibitory, whereas at higher concentrations of PACAP (> 1 nM), the effect of PMA
      was stimulatory. Similar to other agents that elevate cAMP, PACAP38 was an
      effective stimulator of neurite outgrowth. These results show that (a) PACAP27
      and PACAP38 stimulate cAMP accumulation and increase [Ca2+]i through the type I
      PACAP receptors in N1E-115 cells, (b) ionomycin enhances cAMP accumulation by all
      three peptides, and (c) activation of protein kinase C has a dose-dependent
      stimulatory or inhibitory effect on the PACAP38- or PACAP27-stimulated cAMP
      accumulation.

PMID- 8752107
TI  - Low glutathione and high iron govern the susceptibility of oligodendroglial
      precursors to oxidative stress.
AB  - We have previously shown, using qualitative approaches, that oligodendroglial
      precursors are more readily damaged by free radicals than are astrocytes. In the
      present investigation we quantified the oxidative stress experienced by the cells
      using oxidation of dichlorofluorescin diacetate to dichlorofluorescein as a
      measure of oxidative stress; furthermore, we have delineated the physiological
      bases of the difference in susceptibility to oxidative stress found between
      oligodendroglial precursors and astrocytes. We demonstrate that (a)
      oligodendroglial precursors under normal culture conditions are under six times
      as much oxidative stress as astrocytes, (b) oxidative stress experienced by
      oligodendroglial precursors increases sixfold when exposed to 140 mW/m2 of blue
      light, whereas astrocytic oxidative stress only doubles, (c) astrocytes have a
      three times higher concentration of GSH than oligodendroglial precursors, (d)
      oligodendroglial precursors have > 20 times higher iron content than do
      astrocytes, and (e) oxidative stress in oligodendroglial precursors can be
      prevented either by chelating intracellular free iron or by raising intracellular
      GSH levels to astrocytic values. We conclude that GSH plays a central role in
      preventing free radical-mediated damage in glia.

PMID- 8752108
TI  - Modulation of zeta-protein kinase C by cyclic AMP in PC12 cells occurs through
      phosphorylation by protein kinase A.
AB  - Although cyclic AMP (cAMP) has been reported to cross talk with the protein
      kinase C (PKC) system, effects of elevated intracellular cAMP on the activities
      of specific PKC isoforms have not been studied. We report findings from a
      permeabilized cell assay that was used to examine changes in the activity of the
      atypical PKC isoforms brought about by exposure of PC12 cells to agents that
      elevate intracellular cAMP. We found that increases in intracellular cAMP led to
      rapid stimulation of atypical PKC activity, 40-70% above control, for a sustained
      period of time, a response that occurred independent of the phorbol 12-myristate
      13-acetate (PMA)-sensitive PKC isoforms. Changes in intracellular cAMP levels
      resulted in a dose-dependent redistribution of zeta-PKC to the cytoplasm with a
      concomitant increase in the phosphorylation state of the enzyme. Incubation of
      purified zeta-PKC with increasing concentrations of PKA likewise caused a twofold
      increase in the phosphorylation state of zeta-PKC. In contrast to the positive
      effect that PKA-mediated phosphorylation had on the activity of zeta-PKC, the
      enzyme displayed reduced binding to ras when phosphorylated. Taken together,
      these findings are consistent with the hypothesis that protein phosphorylation of
      PKC acts as a positive effector of its enzyme activity and may serve as a
      negative modulator for interaction with other proteins.

PMID- 8752109
TI  - Retinoic acid increases hydroxyindole-O-methyltransferase activity and mRNA in
      human Y-79 retinoblastoma cells.
AB  - Hydroxyindole-O-methyltransferase (HIOMT) plays an important role as the final
      enzyme in the synthesis of melatonin. Here we present the first evidence that
      retinoic acid (RA) stereoisomers are potent regulators of HIOMT in the human
      retinoblastoma-derived Y-79 cell line. Treatment with all-trans-, 13-cis-, and 9
      cis-RA induced a gradual 10-fold increase in HIOMT activity and mRNA, without
      changing the levels of mRNA encoding glyceraldehyde-3-phosphate dehydrogenase,
      actin, S-antigen, and interphotoreceptor retinoid-binding protein. These findings
      point to the possibility that RA may play a physiological role in the regulation
      of human HIOMT.

PMID- 8752110
TI  - Cyanide-induced apoptosis and oxidative stress in differentiated PC12 cells.
AB  - Terminally differentiated PC12 cells are a useful neuron-like model for studying
      programmed cell death in response to nerve growth factor (NGF) deprivation. This
      in vitro model was used to investigate the mechanism by which cyanide-induced
      histotoxic hypoxia produces neuronal degeneration. Treatment of undifferentiated
      PC12 cells with 0.1 mM KCN for 24 h did not produce cell death. In contrast,
      treatment of differentiated PC12 cell cultures with 0.1 mM KCN for 24 h increased
      cell death by 43% when compared with control cultures, as measured by trypan blue
      dye exclusion and lactate dehydrogenase release assays. The Ca2+/Mg(2+)-dependent
      endonuclease inhibitor aurintricarboxylic acid and the transcriptional inhibitor
      actinomycin D partially attenuated hypoxic toxicity, suggesting roles for
      endonuclease activation and transcription in this model of neuronal death.
      Extracted DNA from cyanide-treated neurons demonstrated cleavage into
      oligonucleosomal fragments on gel electrophoresis. Transmission electron
      microscopic analysis showed morphological changes consistent with apoptotic cell
      death, including membrane blebbing and convolution, as well as chromatin
      condensation and margination to the nuclear membrane. Addition of either
      ascorbate or catalase to the cultures partially attenuated the loss of cell
      viability induced by cyanide, and decreased the incidence of apoptotic cells
      after treatment, based on the in situ detection of DNA strand breaks. The ability
      of cyanide to elevate intracellular oxidant species was determined by
      microfluorescence in differentiated PC12 cells loaded with the oxidant-sensitive
      dye 2',7'-dichlorofluorescin. Exposure of cells to 0.1 mM KCN produced a rapid
      generation of oxidants that was blocked approximately 50% by ascorbate or
      catalase. These observations indicate that cyanide induces apoptosis in
      terminally differentiated, and not undifferentiated, PC12 cells, and that
      antioxidants significantly reduce the incidence of cyanide-induced apoptosis.

PMID- 8752111
TI  - A novel transmembrane protein with epidermal growth factor and follistatin
      domains expressed in the hypothalamo-hypophysial axis of Xenopus laevis.
AB  - Through the use of a screening strategy designed to isolate novel cDNAs encoding
      proteins concerned with pituitary secretion in Xenopus laevis, we discovered
      clone X7365, which encodes a transmembrane protein with a signal peptide, two
      follistatin modules, a unique epidermal growth factor domain, and a short
      cytoplasmic region. RNA expression analyses indicated that the X7365 transcript
      is enriched in neuroendocrine tissues. Immunohistochemical studies demonstrated
      that, in addition to being expressed in the optic tectum and in astrocytes in the
      optic nerve, the X7365 protein is concentrated in a discrete population of
      hypothalamic magnocellular neurons. Axons projecting to the median eminence and
      the neurointermediate lobe of the pituitary were also immunopositive, suggesting
      that X7365 functions in the regulation of magnocellular neurosecretion.

PMID- 8752112
TI  - Extracellular calcium has distinct effects on fast and slow components of the
      depolarization-induced secretory response from chromaffin cells.
AB  - An increase in extracellular Ca2+ concentration from 0.25 to 10 mM enhanced
      secretion of norepinephrine and epinephrine induced by a high extracellular K+
      concentration (75 mM). The increment in extracellular Ca2+ concentration also
      increased the observed peak inward Ca2+ current in response to long (10-s)
      depolarizing pulses from a holding potential of -55 mV to +5 mV, from about -26
      to -400 pA. However, the total amount of Ca2+ influx into the cell only increased
      when the extracellular Ca2+ concentration was raised from 0.25 to 1 mM and then
      remained constant up to 10 mM extracellular Ca2+. ATP is cosecreted with
      catecholamines following a depolarizing stimulus. Kinetic studies indicated that
      ATP secretion had two components with time constants, in the presence of 2.5 mM
      extracellular Ca2+, of approximately 4 and 41 s, being the fast component of
      secretion produced by the exocytosis of approximately 220 chromaffin granules.
      The results suggest that, for a given depolarizing stimulus, the size and rate of
      release for the fast and slow components of secretion are dependent on
      extracellular Ca2+ concentration.

PMID- 8752113
TI  - Development of NADPH-diaphorase in the avian retina: regulation by calcium ions
      and relation to nitric oxide synthase.
AB  - Nitric oxide plays an important role as an intercellular messenger in the CNS. In
      the present work we measured NADPH-diaphorase activity, which is considered to be
      a marker of cells producing nitric oxide, in homogenates of the developing chick
      retina. The enzyme activity can be detected beginning in 8-day-old embryonic
      retinas with no further quantitative variations throughout development. Arginine
      analogues inhibit approximately 65% of the activity in embryonic retinas and 50%
      in posthatched retinas. The enzyme is stimulated 50% by 2 mM calcium chloride in
      retinas from 8 to 14 embryonic days, but this effect decreases to 20% in 17-day
      embryonic retinas and practically disappears in posthatched animals. The
      stimulation by calcium is completely blocked by arginine analogues. The decrease
      in enzyme activity at posthatched retinas is not due to stimulation by endogenous
      calcium or the presence of insufficient amounts of calmodulin, because addition
      of EGTA or calmodulin, respectively, did not restore the stimulation to levels
      observed at embryonic stages. Inhibition of NADPH-diaphorase activity by NG-nitro
      L-arginine or L-NG-(iminoethyl) ornithine is concentration dependent with IC50
      values of approximately 1 mM at all stages studied. However, in the presence of
      calcium, the inhibition by both analogues is shifted to the left and is
      apparently biphasic at all developmental stages, including in posthatched
      animals, with IC50 values in the low micromolar range. NADPH-diaphorase was also
      detected by histochemistry in specific groups of cells in the early embryonic
      retina and in subsets of amacrine and ganglion cells, as well as in
      photoreceptors, in more developed retinas. The results indicate that different
      isoforms of nitric oxide synthase are present in the chick retina and that a
      calcium-dependent isoform is predominant in early periods of development.

PMID- 8752114
TI  - Inactivation of brain tryptophan hydroxylase by nitric oxide.
AB  - Tryptophan hydroxylase, the initial and rate-limiting enzyme in the biosynthesis
      of the neurotransmitter serotonin, is inactivated by nitric oxide (NO) and by the
      NO generators sodium nitroprusside, diethylamine/NO, S-nitroso-N
      acetylpenicillamine, and S-nitrosocysteine. The inactivation occurs in an oxygen
      free environment and is enhanced by dithiothreitol and ascorbic acid. Protection
      against the effect of NO on tryptophan hydroxylase is afforded by oxyhemoglobin,
      reduced glutathione, and exogenous Fe(II). Catalase partially protects the enzyme
      from NO-induced inactivation, whereas both superoxide dismutase and uric acid are
      without effect. These findings indicate that tryptophan hydroxylase is a target
      for NO and suggest that critical iron-sulfur groups in this enzyme serve as the
      substrate for NO-induced nitrosylation of the protein, resulting in enzyme
      inactivation.

PMID- 8752115
TI  - Neurochemical evidence that postsynaptic nucleus accumbens D3 receptor
      stimulation enhances cocaine reinforcement.
AB  - The mechanism by which two D3 receptor-preferring agonists, 7
      hydroxydipropylaminotetralin (7-OH-DPAT) and quinelorane, modulate cocaine
      reinforcement was examined by monitoring nucleus accumbens dopamine levels with
      in vivo microdialysis while rats intravenously self-administered the following
      four different drug solutions consecutively: (1) cocaine; (2) a combination of
      cocaine plus a low dose of either agonist; (3) either agonist alone; and finally,
      (4) a physiological saline solution. Both 7-OH-DPAT (4 micrograms/infusion) and
      quinelorane (0.25 microgram/infusion) decreased cocaine (0.25 mg/infusion) intake
      in a manner indicating an enhancement of cocaine reinforcement and simultaneously
      decreased the cocaine-induced elevations in nucleus accumbens dopamine levels by
      > 50%. Subsequent self-administration of either 7-OH-DPAT (4 micrograms/infusion)
      or quinelorane (0.25 microgram/infusion) alone resulted in significant, but
      stable, increases in drug intake, with a concurrent decrease in nucleus accumbens
      dopamine levels to approximately 50% below nondrug baseline levels. These
      findings indicate that postsynaptic D3 receptor stimulation in the nucleus
      accumbens enhances the reinforcing properties of cocaine. In a second experiment,
      local application of 7-OH-DPAT via reverse dialysis (30 and 100 nM perfusate
      concentrations) dose-dependently decreased nucleus accumbens dopamine efflux to
      76 +/- 3.9 and 61 +/- 6.3% of baseline, respectively, whereas there was no effect
      of this agonist on dopamine efflux in the ipsilateral striatum of these same
      animals. Coperfusion with the D3 receptor-preferring antagonist nafadotride dose
      dependently blocked the effect of 7-OH-DPAT on nucleus accumbens dopamine efflux.
      These results suggest that, at low concentrations, 7-OH-DPAT selectively
      activates D3 receptors in vivo.

PMID- 8752117
TI  - Effects of steroid exposure on ligand binding and functional activities of
      diverse nicotinic acetylcholine receptor subtypes.
AB  - Nicotinic acetylcholine receptors (nAChR) are diverse members of the ligand-gated
      ion channel superfamily of neurotransmitter receptors and play critical roles in
      chemical signaling throughout the nervous system. The present study tests whether
      nAChR are potential targets for steroids. Acute or short-term (5 min) preexposure
      to steroids such as progesterone (which acts most potently), estradiol,
      corticosterone, or dexamethasone inhibits function of human muscle-type (alpha 1
      beta 1 gamma delta) or ganglionic (alpha 3 beta 4) nAChR measured using 86Rb+
      efflux assays in TE671/RD clonal or SH-SY5Y neuroblastoma cells. Absolute (high
      nanomolar to intermediate micromolar range) and rank-order potencies for steroid
      mediated functional inhibition are similar across nAChR subtypes but differ for
      some steroid derivatives. At concentrations that produce blockade of nAChR
      function, steroids do not affect binding of radioligands such as 125I-labeled
      alpha-bungarotoxin or [3H] acetylcholine to muscle-type or ganglionic nAChR or to
      neuronal toxin-binding nAChR that contain alpha 7 subunits (alpha 7-nAChR).
      Steroid-mediated blockade of nAChR function is insurmountable by increasing
      agonist concentrations, and cell-impermeant progesterone:bovine serum albumin
      conjugates have full potency as inhibitors of ganglionic or muscle-type nAChR
      function. Chronic (48 h) exposure to progesterone or estradiol, but not the other
      steroids, also produces blockade of nAChR function, without significant effects
      on numbers of nAChR radioligand-binding sites. Collectively, these results
      suggest that steroids act noncompetitively at extracellular sites to inhibit
      nAChR function with unique potencies for different steroid-nAChR subtype
      combinations. Thus, nAChR could be among the targets mediating physiologically
      relevant effects of steroid action in the nervous system.

PMID- 8752116
TI  - Mechanism of catecholamine synthesis inhibition by neuropeptide Y: role of Ca2+
      channels and protein kinases.
AB  - We have previously demonstrated that neuropeptide Y (NPY) inhibits depolarization
      stimulated catecholamine synthesis in rat pheochromocytoma (PC12) cells
      differentiated to a sympathetic neuronal phenotype with nerve growth factor
      (NGF). The present study uses multiple selective Ca2+ channel and protein kinase
      agonists and antagonists to elucidate the mechanisms by which NPY modulates
      catecholamine synthesis as determined by in situ measurement of DOPA production
      in the presence of the decarboxylase inhibitor m-hydroxybenzylhydrazine (NSD
      1015). The L-type Ca2+ channel blocker nifedipine inhibited the depolarization
      induced stimulation of DOPA production by approximately 90% and attenuated the
      inhibitory effect of NPY. In contrast, the N-type Ca2+ channel blocker omega
      conotoxin GVIA inhibited neither the stimulation of DOPA production nor the
      effect of NPY. Antagonism of Ca2+/calmodulin-dependent protein kinase (CaM
      kinase) greatly inhibited the stimulation of DOPA production by depolarization
      and prevented the inhibitory effect of NPY, whereas alterations in the cyclic AMP
      dependent protein kinase pathway modulated DOPA production but did not prevent
      the effect of NPY. Stimulation of Ca2+/phospholipid-dependent protein kinase
      (PKC) with phorbol 12-myristate 13-acetate (PMA) did not affect the basal rate of
      DOPA production in NGF-differentiated PC12 cells but did produce a concentration
      dependent inhibition of depolarization-stimulated DOPA production. In addition,
      NPY did not produce further inhibition of DOPA production in the presence of PMA,
      and the inhibition by both PMA and NPY was attenuated by the specific PKC
      inhibitor chelerythrine. These results indicate that NPY inhibits Ca2+ influx
      through L-type voltage-gated Ca2+ channels, possibly through a PKC-mediated
      pathway, resulting in attenuation of the activation of CaM kinase and inhibition
      of depolarization-stimulated catecholamine synthesis.

PMID- 8752118
TI  - Alterations in serotonin parameters in brain of thiamine-deficient rats are
      evident prior to the appearance of neurological symptoms.
AB  - Biochemical alterations of serotoninergic parameters have been demonstrated in
      experimental thiamine deficiency. In addition, hypophagia and hypothermia, two
      physiological processes associated with changes in the serotonin [5
      hydroxytryptamine (5-HT)] system, are manifest early during the progression of
      thiamine deficiency. The binding of selected 5-HT radioligands was therefore
      investigated in discrete brain regions of pyrithiamine-induced thiamine-deficient
      rats. Using quantitative receptor autoradiography, the binding of 8-hydroxy-2-(di
      n-[3H]propylamino) tetralin, a ligand used to label the somatodendritic 5-HT1A
      autoreceptor of the dorsal raphe nucleus, was found to be unaffected in this
      region, suggesting that the structural integrity of the 5-HT cell bodies is
      maintained throughout the course of pyrithiamine treatment. Increased binding of
      [3H]-ketanserin was observed in regions considered vulnerable as well as in some
      considered to be nonvulnerable during the course of thiamine deficiency. These
      binding changes, which appear to represent changes in the density of the
      postsynaptic 5-HT2A receptor population rather than the "tetrabenazine-sensitive"
      vesicular monoamine transporter, are evident before the appearance of
      histopathologic lesions and coincide with altered tissue concentrations of 5-HT.
      These data suggest that 5-HT neurons, although structurally intact, are
      functionally affected early during the progression of thiamine deficiency. These
      alterations, which are likely a part of adaptive neuronal change consequent to
      thiamine dysfunction, may be important in the physiological manifestations and
      the learning deficits commonly encountered in experimental thiamine deficiency.

PMID- 8752119
TI  - Differential regulation of hippocampal neurotrophins during aging in rats.
AB  - Neurotrophins are a family of neurotrophic factors with considerable structural
      homology. We used sensitive and specific two-site enzyme immunoassays to assess
      age-associated changes in levels of three neurotrophins++-+-nerve growth factor
      (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3)--in
      the hippocampus of Fischer 344 rats. Expressions of these proteins and their
      mRNAs were compared in the same animals. More than 200 ng of BDNF per gram of
      tissue was detected in the hippocampus of 2-month-old rats. This amount was two
      and 100 times greater than that of NT-3 and NGF, respectively. The levels of BDNF
      and NT-3 increased further 2-6 months after birth, whereas NGF content declined
      during this period, and the altered protein levels of all three neurotrophins
      were maintained 6-18 months postnatally. In contrast to the patterns of protein
      expression, BDNF mRNA levels increased during both of these periods, and the NT-3
      mRNA levels appeared to decline. Changes in the expression of BDNF mRNA and NGF
      protein were opposite to those reported to occur in Alzheimer's disease. These
      results suggest that, during normal aging in rats, neurotrophin expression is
      regulated independently at both the mRNA and posttranslational levels. Any
      deficiency in their regulation might contribute to neurodegenerative disorders.

PMID- 8752121
TI  - Receptor-mediated activation of G proteins is increased in postmortem brains of
      bipolar affective disorder subjects.
AB  - Guanine nucleotide binding proteins (G proteins) have been implicated in the
      pathophysiology of bipolar affective disorder. In the present investigation
      receptor-mediated G protein activation and changes in G protein trimeric state
      were examined in frontal cortical membranes obtained from postmortem brains of
      bipolar affective disorder subjects and from age-, sex-, and postmortem interval
      matched controls. Stimulation of cortical membranes with serotonin,
      isoproterenol, or carbachol increased guanosine 5'-O-(3-[35S]thiophosphate)
      ([35S]GTP gamma S) binding to specific G alpha proteins in a receptor-selective
      manner. The abilities of these receptor agonists to stimulate the binding of
      [35S]GTP gamma S to the G alpha proteins was enhanced in membranes from bipolar
      brains. Immunoblot analyses showed increases in the levels of membrane 45- and 52
      kDa G alpha S proteins but no changes in the amounts of G alpha i, G alpha o, G
      alpha Z, G alpha q/11, or G beta proteins in membrane or cytosol fractions of
      bipolar brain homogenates. Pertussis toxin (PTX)-activated ADP-ribosylations of G
      alpha i and G alpha o were enhanced by approximately 80% in membranes from
      bipolar compared with control brains, suggesting an increase in the levels of the
      trimeric state of these G proteins in bipolar disorder. Serotonin-induced,
      magnesium-dependent reduction in PTX-mediated ADP-ribosylation of G alpha i/G
      alpha o in cortical membranes from bipolar brains was greater than that observed
      in controls, providing further evidence for enhanced receptor-G protein coupling
      in bipolar brain membranes. In addition, the amounts of G beta proteins that
      coimmunoprecipitated with the G alpha proteins were also elevated in bipolar
      brains. The data show that in bipolar brain membrane there is enhanced receptor-G
      protein coupling and an increase in the trimeric state of the G proteins. These
      changes may contribute to produce exaggerated transmembrane signaling and to the
      alterations in affect that characterize bipolar affective disorder.

PMID- 8752122
TI  - Activity of ionotropic glutamate receptors in retinal cells: effect of
      ascorbate/Fe(2+)-induced oxidative stress.
AB  - The effect of oxidative stress induced by the oxidant pair ascorbate/Fe2+ on the
      activity of ionotropic glutamate receptors was studied in cultured chick retina
      cells. The release of [3H]GABA and the increase of the intracellular free Na+
      concentration ([Na+]i), evoked by glutamate receptor agonists, were used as
      functional assays for the activity of the receptors. The results show that the
      maximal release of [3H]GABA evoked by kainate (KA; approximately 20% of the
      total) or AMPA (approximately 11% of the total) was not different in control and
      peroxidized cells, whereas the EC50 values determined for peroxidized cells (33.6
      +/- 1.7 and 8.0 +/- 2.0 microM for KA and AMPA, respectively) were significantly
      lower than those determined under control conditions (54.1 +/- 6.6 and 13.0 +/-
      2.2 microM for KA and AMPA, respectively). The maximal release of [3H]GABA evoked
      by NMDA under K+ depolarization was significantly higher in peroxidized cells
      (7.5 +/- 0.5% of the total) as compared with control cells (4.0 +/- 0.2% of the
      total), and the effect of oxidative stress was significantly reduced by a
      phospholipase A2 inhibitor or by fatty acid-free bovine serum albumin. The change
      in the intracellular [Na+]i evoked by saturating concentrations of NMDA under
      depolarizing conditions was significantly higher in peroxidized cells (8.9 +/-
      0.6 mM) than in control cells (5.9 +/- 1.0 mM). KA, used at a subsaturating
      concentration (35 microM), evoked significantly greater increases of the [Na+]i
      in peroxidized cells (11.8 +/- 1.7 mM) than in control cells (7.1 +/- 0.8 mM). A
      saturating concentration (150 microM) of this agonist triggered similar increases
      of the [Na+]i in control and peroxidized cells. Accordingly, the maximal number
      of binding sites for (+)-5-[3H]methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten
      5,10- imine 11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate ([3H]MK-801)
      was increased after peroxidation, whereas the maximal number of binding sites for
      [3H]KA was not affected by oxidative stress. These data suggest that under
      oxidative stress the activity of the ionotropic glutamate receptors is increased,
      with the NMDA receptor being the most affected by peroxidation.

PMID- 8752120
TI  - Detection and quantitation of perlecan mRNA levels in Alzheimer's disease and
      normal aged hippocampus by competitive reverse transcription-polymerase chain
      reaction.
AB  - Our previous studies have implicated perlecan, a specific heparan sulfate
      proteoglycan, in the pathogenesis of fibrillar beta-amyloid protein (A beta)
      accumulation and persistence in Alzheimer's disease (AD) brain. In the present
      investigation, we determined if perlecan mRNA was present in rodent and human
      brain tissue and whether perlecan persistence in A beta amyloid deposits in AD
      hippocampus may be partly due to increased perlecan expression and/or decreased
      perlecan degradation. To detect and to quantify low-abundance perlecan mRNA in
      rodent and postmortem human brain tissue, regions of perlecan domain I (503 and
      366 bp) containing the unique heparan sulfate glycosaminoglycan attachment sites
      were analyzed by reverse transcription (RT) and polymerase chain reaction (PCR).
      Perlecan mRNA was detected in rodent brain, kidney, and liver and in human AD and
      normal aged frontal cortex. Different-size transcripts of perlecan domain I were
      found, suggesting the existence of alternatively spliced variants of perlecan or
      closely related gene products. Quantitative competitive RT-PCR using a mutant
      perlecan domain I internal standard was used to determine perlecan mRNA levels in
      total RNA isolated from the hippocampus of 10 AD (mean +/- SEM duration of
      illness, 11.3 +/- 1.4 years) and 10 normal aged controls. No significant
      difference in perlecan mRNA levels from the hippocampus of AD (1.12 +/- 0.29
      amol/500 ng of total RNA) versus normal aged controls (1.09 +/- 0.30 amol/500 ng
      of total RNA) was found, indicating that perlecan expression remained at steady
      state levels. These results therefore suggest that perlecan persistence in A beta
      amyloid deposits in late-stage AD may be primarily due to decreased perlecan
      degradation and removal.

PMID- 8752123
TI  - Changes of activity and isozyme pattern of phosphofructokinase in the brains of
      patients with Alzheimer's disease.
AB  - A severe reduction of the in vivo cerebral glucose consumption rate is generally
      found in patients with Alzheimer's disease. In postmortem studies changes in the
      activities of key regulatory glycolytic enzymes, including 6-phosphofructokinase
      (PFK), have been reported in Alzheimer's disease brains, but the results obtained
      so far are inconsistent and controversial. We reevaluated the activity of PFK in
      brain tissue from clinically and neuropathologically confirmed cases of
      Alzheimer's disease using optimized tissue disintegration and assay methods and
      determined the PFK isozyme pattern. PFK activity in brains from patients with
      Alzheimer's disease was significantly increased in frontal and temporal cortex
      and unchanged in the other brain areas studied when compared with control brains.
      All three PFK isozymes were detected in each of the brain areas studied. In
      brains of Alzheimer's disease patients the level of the C-type PFK was slightly
      reduced at the expense of the M- and L-type subunits. The data presented do not
      support the results of other groups, which reported up to a 90% reduction of PFK
      activity in Alzheimer's disease. In contrast, the data presented clearly rule out
      the suggestion that changes of PFK activity might be one of the causes for the
      reduced glucose consumption in Alzheimer's disease brains.

PMID- 8752124
TI  - Neurotoxicity of a carboxyl-terminal fragment of the Alzheimer's amyloid
      precursor protein.
AB  - We have previously shown that a recombinant carboxyl-terminal 105-amino-acid
      fragment (CT105) of the amyloid precursor protein (APP) induced strong non
      selective inward currents in Xenopus oocytes. Here we investigated the toxic
      effect of CT105 peptide on the cultured mammalian cells. The CT105 peptide
      induced a significant lactate dehydrogenase (LDH) release from cultured rat
      cortical neurons and PC12 cells in a concentration (from 10 microM)- and time
      (from 48 h)-dependent manner. The toxic effect of CT105 was more potent than that
      of any fragments of amyloid beta protein (A beta). However, CT105 peptide did not
      affect the viability of U251 human glioblastoma cells. In contrast to CT105, A
      beta increased LDH release only slightly even at 50 microM but significantly
      inhibited 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction
      at submicromolar concentrations. Among the various neuroprotective drugs tested,
      only cholesterol, which alters membrane fluidity, could attenuate the
      cytotoxicity of CT105 significantly. The CT105 peptide formed multiple self
      aggregates on solubilization. Pretreatment with a sublethal concentration of
      CT105 did not significantly alter the susceptibility of cells to hydrogen
      peroxide and glutamate. Endogenous CT peptides were found not only in the cell
      lysates but also in the conditioned medium of PC12 cells. These results imply
      that CT peptide can directly attack the cell membrane probably by making pores or
      nonselective ion channels, whereas A beta impairs the intracellular metabolic
      pathway first. Thus, it is thought that both CT and A beta, which are formed
      during the processing of APP, may participate in the neuronal degeneration in
      Alzheimer's disease by different mechanisms.

PMID- 8752125
TI  - Polymerization of tau into filaments in the presence of heparin: the minimal
      sequence required for tau-tau interaction.
AB  - Paired helical filaments isolated from the brains of patients with Alzheimer's
      disease are composed of a major protein component, the microtubule-associated
      protein termed tau, together with other nonprotein components, including heparan,
      a glycosaminoglycan, the more extensively sulfated form of which is heparin. As
      some of these nonprotein components may modulate the assembly of tau into
      filamentous structures, we have analyzed the ability of the whole tau protein or
      some of its fragments to self-assemble in the presence of heparin. Different tau
      fragments, all of them containing some sequences of the tubulin-binding motif,
      can assemble in vitro into filaments. We have also found formation of polymers
      with the 18-residue-long peptide corresponding to the third tubulin-binding motif
      of tau. This suggests that the ability of tau for self-assembly could be
      localized in a short sequence of amino acids present in the tubulin-binding
      repeats of the tau molecule.

PMID- 8752126
TI  - Structural motifs encoded by individual exons of the human neurokinin-1 receptor
      gene interact differentially with selective agonists and antagonists.
AB  - Three chimeric receptors were constructed by exchanging exons between human
      neurokinin NK1 and NK3 receptor genes. The N-terminal sequences of these chimeric
      receptors are encoded by exon 1, exon 1-2, or exon 1-3 of the NK1 receptor gene,
      whereas the remaining C-terminal sequences of these chimeric receptors are
      encoded by corresponding exons of the human NK3 receptor gene. Substance P bound
      with high affinities to all three chimeric receptors, suggesting that in addition
      to the common structures composed of conserved amino acid residues among
      neurokinin receptors, structural elements encoded by the first exon of the human
      NK1 receptor gene may also play an important role for substance P binding. On the
      contrary, potent NK1 antagonists L703,606 and SR140,333 did not show any
      detectable binding to these chimeric receptors. In accordance, sequences encoded
      by exon 4, and possibly exon 5, are likely to contain important structural motifs
      that may directly or indirectly influence the binding of these antagonists.
      Further comparison of the binding affinities of highly selective NK1 agonists,
      [Sar9, Met(O2)11] substance P, substance P methyl ester, and septide, revealed
      that each agonist may interact differently with the human NK1 receptor. These
      results show that the exon-exchanging technique can be a useful tool for studying
      structure-function relationships of receptors in which exon-intron junctions are
      fully conserved among receptor subtypes.

PMID- 8752127
TI  - Investigations into the mechanism of action of a novel nitric oxide generator on
      cellular respiration.
AB  - Nitric oxide may regulate cellular respiration by competition with oxygen at
      mitochondrial cytochrome oxidase. Using an astrocyte-derived cell line, we have
      compared the mechanism of action of the nitric oxide-generating compound
      Roussin's black salt with that of sodium nitroprusside on cellular oxygen
      consumption. Intense light exposure induced the release of large quantities of
      nitric oxide from both of the donor compounds. However, in room light only
      Roussin's black salt generated low levels of the radical. Simultaneous
      measurement of oxygen consumption and of nitric oxide production demonstrated
      that sodium nitroprusside only had inhibitory actions when exposed to intense
      light (nitric oxide release), whereas Roussin's black salt had inhibitory actions
      in room light. Extracellular haemoglobin did not prevent the inhibition of
      respiration rate induced by Roussin's black salt even though stimulation of
      nitric oxide release on light exposure was markedly reduced. Preincubation of
      cells with Roussin's black salt and subsequent measurement of levels of light
      liberated nitric oxide demonstrated that the compound was rapidly internalised.
      The uptake of sodium nitroprusside was minimal. These data suggest that, in
      contrast to sodium nitroprusside, the cellular internalisation of Roussin's black
      salt allows site-directed nitric oxide release and very effective inhibition of
      cellular respiration.

PMID- 8752128
TI  - Fimbria-fornix transections selectively down-regulate subtypes of glutamate
      transporter and glutamate receptor proteins in septum and hippocampus.
AB  - The effects of CNS axotomy on glutamate transporter and glutamate receptor
      expression were evaluated in adult rats following unilateral fimbria-fornix
      transections. The septum and hippocampus were collected at 3, 7, 14, and 30 days
      postlesion. Homogenates were immunoblotted by using antibodies directed against
      glutamate transporters (GLT-1, GLAST, and EAAC1) and glutamate receptors (GluR1,
      GluR2/3, GluR6/7, and NMDAR1), and they were assayed for glutamate transport by D
      [3H]aspartate binding. GLT-1 was decreased at 7 and 14 days postlesion within the
      ipsilateral septum and at 7 days postlesion in the hippocampus. GLAST was
      decreased within the ipsilateral septum and hippocampus at 7 and 14 days
      postlesion. No postlesion alterations in EAAC1 immunoreactivity were observed. D
      [3H]Aspartate binding was decreased at 7, 14, and 30 days postlesion within the
      ipsilateral septum and 14 days postlesion in the hippocampus. GluR2/3 expression
      was down-regulated at 30 days postlesion within the ipsilateral septum, whereas
      GluR1, GluR6/7, and NMDAR1 immunoreactivity was unchanged. In addition, no
      alterations in glutamate receptor expression were detected within hippocampal
      homogenates. This study demonstrates a selective down-regulation of primarily
      glial, and not neuronal, glutamate transporters and a delayed, subtype-specific
      down-regulation of septal GluR2/3 receptor expression after regional
      deafferentation within the CNS.

PMID- 8752129
TI  - Differential regulation of phenylethanolamine N-methyltransferase expression in
      two distinct subpopulations of bovine chromaffin cells.
AB  - Chromaffin cells were isolated from bovine adrenal glands and fractionated into
      two distinct subpopulations by density gradient centrifugation on Percoll. Cells
      in the more dense fraction stored epinephrine (E) as their predominant
      catecholamine (81% of total catecholamines), contained high levels of
      phenylethanolamine N-methyltransferase (PNMT) activity, and exhibited intense
      PNMT immunoreactivity. This population of chromaffin cells was termed the E-rich
      cell population. Cells in the less dense fraction, the norepinephrine (NE)-rich
      cell population, stored predominantly NE (75% of total catecholamines). Although
      the NE-rich cells had only 3% as much PNMT activity as did the E-rich cells, 20%
      of the NE-rich cells were PNMT immunoreactive. This suggested that the PNMT
      positive cells in the NE-rich cell cultures contained less PNMT per cell than did
      E-rich cells and may not be typical adrenergic cells. The regulation of PNMT mRNA
      levels and PNMT activity in primary cultures of E-rich and NE-rich cells was
      compared. At the time the cells were isolated, PNMT mRNA levels in NE-rich cells
      were approximately 20% of those in E-rich cells; within 48 h in culture, PNMT
      mRNA in both populations declined to almost undetectable levels. Treatment with
      dexamethasone increased PNMT mRNA levels and PNMT activity in both populations.
      In E-rich cells, dexamethasone restored PNMT mRNA to the level seen in freshly
      isolated cells and increased PNMT activity twofold. In NE-rich cells,
      dexamethasone increased PNMT mRNA to levels twice those found in freshly isolated
      cells and increased PNMT activity sixfold. Cycloheximide blocked the effects of
      dexamethasone on PNMT mRNA expression in NE-rich cells but had little effect in E
      rich cells. Angiotensin II, forskolin, and phorbol 12,13-dibutyrate elicited
      large increases in PNMT mRNA levels in E-rich cells but had no effect in NE-rich
      cells. Our data suggest that PNMT expression is regulated differently in the two
      chromaffin cell subpopulations.

PMID- 8752131
TI  - Tau is widely expressed in rat tissues.
AB  - The microtubule-associated protein tau, a major component of paired helical
      filaments in Alzheimer's disease, had been thought to be a neuron-specific
      protein. We investigated various rat tissues using both reverse transcriptase
      coupled polymerase chain reaction and immunoblotting. tau was found to be widely
      expressed in many tissues besides the nervous system: at relatively high levels
      in the heart, skeletal muscle, lung, kidney, and testis and at low levels in the
      adrenal gland, stomach, and liver. In terms of the tau isoform expression,
      tissues fall into three classes: those expressing predominantly small tau, those
      expressing predominantly big tau, and those expressing both at comparable levels.
      The phosphorylation state of tau varied among the tissues, as shown by
      differences in the extents of changes in the reactivities with Tau 1 and
      electrophoretic mobilities after dephosphorylation. It is notable that tau in
      many nonneural tissues was highly phosphorylated at Ser396 (according to the
      numbering of the 441-residue human tau isoform). Thus, tau is widely expressed in
      rat tissues.

PMID- 8752130
TI  - Slow axonal transport of soluble actin with actin depolymerizing factor, cofilin,
      and profilin suggests actin moves in an unassembled form.
AB  - We examined the axonal transport of actin and its monomer binding proteins, actin
      depolymerizing factor, cofilin, and profilin, in the chicken sciatic nerve
      following injection of [35S]methionine into the lumbar spinal cord. At intervals
      up to 20 days after injection, nerves were cut into 1-cm segments and separated
      into Triton X-100-soluble and particulate fractions. Actin and its binding
      proteins were then isolated by affinity chromatography on DNase I-Sepharose and
      by one- and two-dimensional polyacrylamide gel electrophoresis. Fluorographic
      analysis showed that the specific activity of soluble actin was two to three
      times that of its particulate form and that soluble actin, cofilin, actin
      depolymerizing factor, and profilin were transported at similar rates in slow
      component b of axonal flow. Our data strongly support the view that the mobile
      form of actin in slow transport is soluble and that a substantial amount of this
      actin may travel as a complex with actin depolymerizing factor, cofilin, and
      profilin. Along labeled nerves the specific activity of the unphosphorylated form
      of actin depolymerizing factor, which binds actin, was not significantly
      different from that of its "inactive" phosphorylated form. This constancy in
      specific activity suggests that continuous inactivation and reactivation of actin
      depolymerizing factor occur during transport, which could contribute to the
      exchange of soluble actin with the filamentous actin pool.

PMID- 8752132
TI  - Carbachol inhibits insulin-stimulated phosphatidylinositol 3-kinase activity in
      SH-SY5Y neuroblastoma cells.
AB  - SH-SY5Y human neuroblastoma cells express muscarinic M3 receptors as well as
      insulin receptors, thus offering the opportunity to investigate possible cross
      talk following activation of two distinct intracellular signal transduction
      pathways that convert the precursor phosphatidylinositol (PI) to its 3' phosphate
      or its 4' phosphate, respectively. In this study, the effect of carbachol on
      insulin-stimulated PI 3-kinase (PI3K) activity was examined in SH-SY5Y cells.
      Insulin addition to the cell medium induced a 10-26-fold increase in anti
      phosphotyrosine-immunoprecipitable PI3K activity. Preincubation with 1 mM
      carbachol inhibited the insulin-stimulated PI3K activity in a time-dependent
      manner, with half-maximal and maximal inhibition times of 4 and 15 min,
      respectively. Atropine blocked the inhibitory effect of carbachol. Although
      carbachol did not change the amount of 85-kDa subunit protein regulatory unit
      associated with tyrosine-phosphorylated proteins, either in control or in insulin
      stimulated cells, it appears to decrease the amount of associated 110-kDa
      catalytic subunit protein in the latter instance. Because PI3K activity from SH
      SY5Y cells has been shown to be inhibited in vitro in the presence of cytidine
      diphosphodiacylglycerol (CDP-DAG) or phosphatidate (PA), we examined the presence
      of these lipids in SH-SY5Y cells that had been treated with carbachol. Formation
      of both lipids was increased in a time-dependent manner following carbachol
      addition, and their increased levels are proposed to account for the observed in
      vivo inhibition of PI3K. Addition of the cell-permeable homologue didecanoyl-CDP
      DAG to intact cells inhibited insulin-stimulated PI3K activity up to 75%, with an
      IC50 of 0.5 microM, a result that further supports a proposed lipid-mediated
      inhibition of PI3K. Exogenously added didecanoyl-PA, however, did not affect PI3K
      activity. The possibility that stimulation of the PI 4-kinase-mediated signal
      transduction pathway leads to down-regulation of the PI3K-mediated signal
      transduction pathway in vivo, via inhibition of PI3K by CDP-DAG or by other
      consequences of phosphoinositidase C-linked receptor activation, is discussed.

PMID- 8752133
TI  - Connexin43 is another gap junction protein in the peripheral nervous system.
AB  - That many cells express more than one connexin (Cx) led us to examine whether Cxs
      other than Cx32 are expressed in the PNS. In addition to Cx32 mRNA, Cx43 and Cx26
      mRNAs were detected in rat sciatic nerve by northern blot analysis. Cx43 mRNA,
      but not Cx26 mRNA, was expressed in both the primary Schwann cell culture and
      immortalized Schwann cell line (T93). The steady-state levels of the Cx43 mRNA in
      the primary Schwann cell culture increased 2.0-fold with 100 microM forskolin,
      whereas that of Po increased 7.0-fold. Immunoreactivity to Cx43 was detected on
      western blots of cultured Schwann cells, T93 cells, and sciatic nerves but not on
      blots of PNS myelin. Immunohistochemical study using human peripheral nerves
      revealed that anti-Cx43 antibody stained cytoplasm around nucleus of Schwann
      cells but not myelin, confirming western blot results. Although Po expression was
      markedly decreased by crush injury of the sciatic nerves, Cx43 expression showed
      no apparent change. Developmental profiles showed that Cx43 expression in the
      sciatic nerve increased rapidly after birth, peaked at about postnatal day 6, and
      then decreased gradually to a low level. In adult rats, the Cx43 mRNA value was
      much lower than that of Cx32. These findings suggest that Cx43 is localized in
      Schwann cell bodies and that, compared with Po, its expression is less influenced
      by axonal contact and cyclic AMP levels. The high expression on postnatal day 6
      indicates that Cx43 may be related to PNS myelination. Cx43 is another gap
      junction, but its function appears to differ from that of Cx32, as judged by the
      differences in their localization and developmental profiles.

PMID- 8752134
TI  - Shift of the cellular oxidation-reduction potential in neural cells expressing
      Bcl-2.
AB  - Expression of the protooncogene bcl-2 inhibits both apoptotic and in some cases
      necrotic cell death in many cell types, including neural cells, and in response
      to a wide variety of inducers. The mechanism by which the Bcl-2 protein acts to
      prevent cell death remains elusive. One mechanism by which Bcl-2 has been
      proposed to act is by decreasing the net cellular generation of reactive oxygen
      species. To evaluate this proposal, we measured activities of antioxidant enzymes
      as well as levels of glutathione and pyridine nucleotides in control and bcl-2
      transfectants in two different neural cell lines-rat pheochromocytoma PC12 and
      the hypothalamic GnRH cell line GT1-7. Both neural cell lines overexpressing bcl
      2 had elevated total glutathione levels when compared with control transfectants.
      The ratios of oxidized glutathione to total glutathione in PC12 and GT1-7 cells
      overexpressing bcl-2 were significantly reduced. In addition, the NAD+/NADH ratio
      of bcl-2-expressing PC12 and GT1-7 cells was two- to threefold less than that of
      control cell lines. GT1-7 cells overexpressing bcl-2 had the same level of
      glutathione peroxidase, catalase, superoxide dismutase, and glutathione reductase
      activities as control cells. PC12 cells overexpressing bcl-2 had a twofold
      increase in superoxide dismutase and catalase activity when compared with matched
      control transfected cells. The levels of glutathione peroxidase and glutathione
      reductase in PC12 cells overexpressing bcl-2 were similar to those of control
      cells. These results indicate that the overexpression of bcl-2 shifts the
      cellular redox potential to a more reduced state, without consistently affecting
      the major cellular antioxidant enzymes.

PMID- 8752135
TI  - Repetitive and transient increases in hippocampal neural cell adhesion molecule
      polysialylation state following multitrial spatial training.
AB  - Polysialylated neurons, located at the inner border of the dentate granule cell
      layer, have been demonstrated to exhibit time-dependent change in their frequency
      at 10-12 h following training in the Morris water maze, a spatial learning
      paradigm. Such a change was not observed in animals required to locate a visible
      platform or in those rendered amnesic with scopolamine. This frequency response
      was capable of rapid reactivation following further training stimuli in a manner
      that was independent of circadian influence. These learning-associated
      modulations in neural cell adhesion molecule (NCAM) polysialylation state did not
      increase in magnitude despite improved performance, suggesting their activation
      is required for processing information rather than contributing to previously
      stored, task-associated memory. An increase in NCAM polysialylation appears to be
      a universal learning response to both spatial and nonspatial paradigms as similar
      time-dependent changes occurred following training in a one-trial, step-through,
      passive avoidance response subsequent to water maze training.

PMID- 8752136
TI  - L-[3H]nitroarginine and L-[3H]arginine uptake into rat cerebellar synaptosomes:
      kinetics and pharmacology.
AB  - Characteristics of the transport of the nitric oxide synthase substrate L
      arginine and its inhibitor, NG-nitro-L-arginine (L-NOARG), into rat cerebellar
      synaptosomes were studied. Uptake of both L-arginine and L-NOARG was linear with
      increasing amount of protein (up to 40 micrograms) and time of incubation (up to
      5 min) at 37 degrees C. Uptake of both compounds reached a steady state by 20
      min. Maximal uptake of L-NOARG (650 pmol/mg of protein) was three to four times
      higher than that of L-arginine (170 pmol/mg of protein). L-NOARG uptake showed
      biphasic kinetics (Km1 = 0.72 mM, Vmax 1 = 0.98 nmol/min/mg of protein; Km2 =
      2.57 mM, Vmax2 = 16.25 nmol/min/mg of protein). L-Arginine uptake was monophasic
      with a Km of 106 microM and a Vmax of 0.33 nmol/min/mg of protein. L-NOARG uptake
      was selectively inhibited by L-NOARG, NG-nitro-L-arginine methyl ester, and
      branched-chain and aromatic amino acids. L-Alanine and L-serine also inhibited L
      NOARG uptake but with less potency. Uptake of L-arginine was selectively
      inhibited by NG-monomethyl-L-arginine acetate and basic amino acids. These
      studies suggest that in rat cerebellar synaptosomes, L-NOARG is transported by
      the neutral amino acid carrier systems T and L with high affinity, whereas L
      arginine is transported by the basic amino acid carrier system y+ with high
      affinity. These data indicate that the concentration of competing amino acids is
      an important factor in determining the rates of uptake of L-NOARG and L-arginine
      into synaptosomes and, in this way, may control the activity of nitric oxide
      synthase.

PMID- 8752138
TI  - Presence of pituitary adenylate cyclase-activating polypeptide receptors in Y-79
      human retinoblastoma cells.
AB  - Cytochemical analysis demonstrated that a high percentage of human Y-79
      retinoblastoma cells displayed a specific labeling by the biotinyl derivative of
      pituitary adenylate cyclase-activating polypeptide (PACAP), a novel neuropeptide
      of the secretin-vasoactive intestinal peptide (VIP) family of peptides. In cell
      membranes, the two molecular forms of PACAP, the one with 38 (PACAP 38) and the
      other with 27 (PACAP 27) amino acids, displaced the binding of 125I-PACAP 27 with
      IC50 values in the picomolar range and increased adenylyl cyclase activity by 100
      fold with EC50 values of 27 and 180 pM, respectively. VIP, human peptide
      histidine-isoleucine, glucagon, and secretin were much less effective and potent
      in both receptor assays. The PACAP receptor antagonists PACAP 6-27 and PACAP 6-38
      and an antiserum directed against the stimulatory G protein Gs inhibited the
      PACAP stimulation of adenylyl cyclase. In intact cells, both PACAPs and VIP
      failed to stimulate the phosphoinositide hydrolysis, whereas in cell membranes
      PACAP 38, but not the other peptides, produced a modest increase (40%) of
      inositol phosphate formation with an EC50 value of 22 nM. However, this effect
      was not antagonized by either PACAP 6-38 or PACAP 6-27. These data demonstrate
      the presence in human Y-79 retinoblastoma cells of specific PACAP receptors and
      provide further evidence that PACAP may act as a neurotransmitter/neuromodulator
      in mammalian retina.

PMID- 8752137
TI  - Further identification of neurokinin receptor types and mechanisms of calcium
      signaling evoked by neurokinins in the murine neuroblastoma C1300 cell line.
AB  - It has been suggested that murine neuroblastoma C1300 cells express endogenous
      neurokinin NK2 receptors with features that differ from those of NK2 receptors
      characterized in other systems. In this study, we have further characterized the
      neurokinin receptor types present in this cell line. RNA blots showed that mRNAs
      of NK2 and NK3 receptors, but not of NK1 receptors, were expressed in C1300
      cells. The increase in the cytosolic calcium concentration ([Ca2+]i) induced by
      0.33 microM neurokinin A was completely inhibited by SR 48968, an NK2 receptor
      antagonist, whereas the partial response to 0.33 microM neurokinin B was
      unaffected, and the response was completely inhibited by SR 142801, and NK3
      receptor antagonist. In addition, the [Ca2+]i increase by 0.33 microM senktide,
      an NK3 receptor agonist, was inhibited by SR 142801 but not by SR 48968. These
      findings indicated that C1300 cells endogenously express functional NK2 and NK3
      receptors. It was also demonstrated that NK2 and NK3 receptors can be activated
      independently by 3.3 microM neurokinin A in the presence of 1.0 microM SR 142801
      or 1.0 microM senktide, respectively. Therefore, the mechanisms of Ca2+ signaling
      mediated by endogenous NK2 and NK3 receptors were investigated. The independent
      activation of NK2 or NK3 receptors induced not only the [Ca2+]i increase, but
      also stimulated the formation of inositol trisphosphates; both these responses
      were inhibited by U73122, a phospholipase C (PLC) inhibitor. In addition, NK2 and
      NK3 receptor-mediated [Ca2+]i increase was partially attenuated in the absence of
      extracellular Ca2+ or in the presence of nickel, an inorganic Ca2+ influx
      blocker, but was unaffected by nifedipine and omega-conotoxin, L- and N-type
      voltage-dependent Ca2+ channel blockers, respectively. Furthermore, the
      depolarization by 60 mM K+ did not affect the [Ca2+]i. These findings suggested
      that the NK2 and NK3 receptor-mediated [Ca2+]i increase was due to the activation
      of PLC and was dependent on the mobilization of internal Ca2+ and the entry of
      extracellular Ca2+ through voltage-independent channels. This study showed that
      the C1300 cell line is a useful system with which to investigate pharmacological
      functions and signaling pathways of endogenous NK2 and NK3 receptors.

PMID- 8752139
TI  - The dual peptidase inhibitor RB101 induces a long-lasting increase in the
      extracellular level of Met-enkephalin-like material in the nucleus accumbens of
      freely moving rats.
AB  - This study was carried out to analyze the extracellular levels of Met-enkephalin
      like material in the nucleus accumbens, a brain structure involved in the effects
      of opioids on motor activity and reward processes, using microdialysis in awake
      and freely moving rats, combined with a sensitive radioimmunoassay. The levels of
      Met-enkephalin-like material were measured after administration of a dual
      inhibitor of enkephalin-degrading enzymes, RB101, to evaluate its in vivo
      protecting effects. The basal levels of Met-enkephalin-like immunoreactivity in
      the nucleus accumbens were approximately 1.2 pg/30 min or 2.2 fmol/30 min (37
      pM). Perfusion of KCI (100 mM) produced a 17-fold increase in the level of Met
      enkephalin-like material in this structure. During the 8-h perfusion, which
      started at 9 a.m., a spontaneous increase of the basal level of Met-enkephalin
      like material in the nucleus accumbens occurred between 4 and 4:30 p.m.,
      suggesting the existence of variation in opioid peptide secretion, at least in
      this structure. Intraperitoneal injection of RB101 induced a dose-dependent and
      long-lasting (210-min) increase in the extracellular levels of Met-enkephalin
      like material. A prolonged effect was also observed in the behavioral studies in
      which the inhibitor increased global motor activity of rats 210 min after
      injection. These data represent the first direct evidence that dual inhibitors of
      enkephalin-degrading enzymes increase in vivo the extracellular levels of Met
      enkephalin-like material in awake and freely moving rats.

PMID- 8752140
TI  - Functional coupling of the delta-, mu-, and kappa-opioid receptors to mitogen
      activated protein kinase and arachidonate release in Chinese hamster ovary cells.
AB  - To examine whether the mitogen-activated protein kinase (MAPK) cascade and
      phospholipase A2 (PLA2) are involved in the signal transduction mechanism of the
      opioid receptor, the delta-, mu-, and kappa-opioid receptors were stably
      expressed from cDNA in Chinese hamster ovary cells. Activation of the delta-, mu
      , and kappa-receptors by agonists induced a rapid and transient increase in MAPK
      activity accompanied by reduced electrophoretic mobility of the 42-kDa isoform of
      MAPK (p42), probably owing to phosphorylation. The opioid receptor-mediated
      increase in MAPK activity was suppressed not only by pretreatment with genistein,
      a tyrosine protein kinase inhibitor, but also by prolonged exposure to phorbol 12
      myristate 13-acetate and pretreatment with GF 109203X, a selective protein kinase
      C (PKC) inhibitor, suggesting the involvement of PKC as well as tyrosine protein
      kinase. Furthermore, stimulation of the delta-, mu-, and kappa-receptors with
      opioid agonists in the presence of A23187, a calcium ionophore, resulted in an
      increase in arachidonate release, suggesting that PLA2 is activated by the opioid
      receptors when the intracellular Ca2+ concentration is elevated. Both MAPK
      activation and increase in arachidonate release mediated by the opioid receptors
      were abolished by pretreatment with pertussis toxin, suggesting that these
      responses are mediated by Gi or Go types of GTP-binding regulatory proteins.

PMID- 8752141
TI  - Time-dependent increase in release of arachidonic acid following passive
      avoidance training in the day-old chick.
AB  - We have investigated the role of arachidonic acid, a putative retrograde
      messenger, in a one-trial aversive learning task in the day-old chick. The left
      and right intermediate medial hyperstriatum ventrale (IMHV) in the chick
      forebrain have previously been implicated in the formation of memory for this
      task. Using an ex vivo technique we have determined the concentrations of various
      fatty acids liberated from prisms prepared from these brain regions at different
      time points up to 24 h following passive avoidance training. At 30, 60, and 75
      min posttraining the concentration of arachidonic acid, but not of other fatty
      acids, in prisms prepared from the left IMHV, but not the right IMHV, was
      enhanced compared with that in chicks trained on a nonaversive water-coated bead.
      To test whether arachidonic acid liberation from the left IMHV was receptor
      stimulated we showed that (a) liberation of endogenous arachidonic acid from
      homogenate prepared from the left and right IMHV of untrained chicks was
      stimulated by depolarization with KCl (50 mM) and that (b) glutamate agonists of
      the NMDA and metabotropic subtypes of glutamate receptor stimulated release of
      preloaded [14C] arachidonic acid from prisms prepared from the left IMHV but not
      the right IMHV. These results indicate that arachidonic acid is liberated from
      the left IMHV following passive avoidance training in the day-old chick and may
      play a role as a retrograde messenger in this memory task.

PMID- 8752142
TI  - Clusterin (Apo J) protects against in vitro amyloid-beta (1-40) neurotoxicity.
AB  - Clusterin is a secreted glycoprotein that is markedly induced in many disease
      states and after tissue injury. In the CNS, clusterin expression is elevated in
      neuropathological conditions such as Alzheimer's disease (AD), where it is found
      associated with amyloid-beta (A beta) plaques. Clusterin also coprecipitates with
      A beta from CSF, suggesting a physiological interaction with A beta. Given this
      interaction with A beta, the goal of this study was to determine whether
      clusterin could modulate A beta neurotoxicity. A mammalian recombinant source of
      human clusterin was obtained by stable transfection of hamster kidney fibroblasts
      with pADHC-9, a full-length human cDNA clone for clusterin. Recombinant clusterin
      obtained from this cell line, as well as a commercial source of native clusterin
      purified from serum, afforded dose-dependent neuroprotection against A beta (1
      40) when tested in primary rat mixed hippocampal cultures. Clusterin afforded
      substoichiometric neuroprotection against several lots of A beta (1-40) but not
      against H2O2 or kainic acid excitotoxicity. These results suggest that the
      elevated expression of clusterin found in AD brain may have effects on subsequent
      amyloid-beta plaque pathology.

PMID- 8752143
TI  - Brain S-adenosylmethionine levels are severely decreased in Alzheimer's disease.
AB  - S-Adenosylmethionine is an essential ubiquitous metabolite central to many
      biochemical pathways, including transmethylation and polyamine biosynthesis.
      Reduced CSF S-adenosylmethionine levels in Alzheimer's disease have been
      reported; however, no information is available regarding the status of S
      adenosylmethionine or S-adenosylmethionine-dependent methylation in the brain of
      patients with this disorder. S-Adenosylmethionine concentrations were measured in
      postmortem brain of 11 patients with Alzheimer's disease. We found decreased
      levels of S-adenosylmethionine (-67 to -85%) and its demethylated product S
      adenosylhomocysteine (-56 to -79%) in all brain areas examined (cerebral cortical
      subdivisions, hippocampus, and putamen) as compared with matched controls (n =
      14). S-Adenosylmethionine and S-adenosylhomocysteine levels were normal in
      occipital cortex of patients with idiopathic Parkinson's disease (n = 10),
      suggesting that the decreased S-adenosylmethionine levels in Alzheimer's disease
      are not simply a consequence of a chronic, neurodegenerative condition. Reduced S
      adenosylmethionine levels could be due to excessive utilization in polyamine
      biosynthesis. The severe reduction in levels of this essential biochemical
      substrate would be expected to compromise seriously metabolism and brain function
      in patients with Alzheimer's disease and may provide the basis for the
      observations of improved cognition in some Alzheimer's patients following S
      adenosylmethionine therapy.

PMID- 8752144
TI  - Identification by differential display of annexin-VI, a gene differentially
      expressed during melanoma progression.
AB  - To identify genes involved in the melanocyte to malignant melanoma conversion, we
      have applied differential display to the comparison of syngeneic murine B16F10
      (metastatic melanoma) and Melan-a-immortalized melanocyte cell lines.
      Approximately 7000 bands were analyzed, revealing approximately 80 to be
      differentially displayed. Reverse Northern blotting and subsequent Northern
      blotting confirmed the reproducible differential expression of four transcripts.
      Three B16F10-specific bands encode novel genes or partially sequenced cDNAs of
      unknown function. One Melan-a-specific band was found to be identical to the 3'
      end region of the mouse Annexin VI mRNA and shown to have a reduced message
      expression in B16F10 relative to Melan-a. Differential expression was confirmed
      at the protein level with Western blotting using a rabbit polyclonal antiserum.
      Immunohistochemistry of human melanoma specimens with this antiserum revealed a
      decrease or loss of Annexin VI expression as melanomas progressed from a benign
      to a more malignant phenotype. Our results provide further evidence for a
      potential role of Annexin VI in tumor suppression.

PMID- 8752145
TI  - Tyrphostin AG 1478 preferentially inhibits human glioma cells expressing
      truncated rather than wild-type epidermal growth factor receptors.
AB  - The effects of a new epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitor, tyrphostin AG 1478, were tested on three related human glioma cell
      lines: U87MG, which expressed endogenous wild-type (wt) EGFR, and two
      retrovirally infected U87MG cell populations which over-expressed either wt
      (U87MG.wtEGFR) or truncated EGFR (U87MG. delta EGFR). Although AG 1478 inhibited
      cell growth, DNA synthesis, EGFR tyrosine kinase activity, and receptor
      autophosphorylation of each cell line in a dose-dependent manner, it was
      significantly more potent in U87MG. delta EGFR cells than in the other two cell
      lines. The increased inhibitory response of U87MG. delta EGFR cells was due to a
      greater sensitivity of the constitutively autophosphorylated Mr 140,000 and
      155,000 delta EGFR species to AG 1478. These results suggest that AG 1478 is a
      relatively specific inhibitor of the delta EGFR, and this finding may have
      important therapeutic implications since the delta EGFR occurs frequently in
      glioblastomas and in breast, lung, and ovarian cancers.

PMID- 8752146
TI  - Gain-of-function p53 mutations enhance alteration of the T-cell receptor
      following X-irradiation, independently of the cell cycle and cell survival.
AB  - Missense mutations are by the far the most common types of mutations found in p53
      of human tumors, suggesting that mutant p53 proteins function either by
      abrogating wild-type function or by gaining new oncogenic functions. To
      distinguish between the dominant-negative effect and gain of new function of p53
      missense mutants, we measured the ability of transfected missense mutant p53s in
      p53-null Jurkat cells to alter T-cell receptor (TCR) surface expression. The TCR
      is a key signal transduction moiety common to T lymphocytes and is one of the
      major sites for aberrations in T-cell leukemias/lymphomas. Three p53 mutants
      (248trp, 249ser, and 273his) enhanced the frequency of TCR mutants after graded
      doses of X-radiation compared to null p53 parent- and wild-type p53-possessing
      normal lymphocytes; the parent Jurkat and normal lymphocyte showed no difference.
      These enhancements were not the results of a change in radiosensitivity or in G1
      checkpoint arrest characteristics. Therefore, the creation of this mutator
      phenotype by missense-type p53 mutations implies that a more direct mechanism,
      apart from changes of cell cycle kinetics or cell death, may be responsible for
      the selection of certain p53 point mutations, which eventually result in the
      tumorigenesis of the cell.

PMID- 8752147
TI  - delta 12-Prostaglandin-J2 is cytotoxic in human malignancies and synergizes with
      both cisplatin and radiation.
AB  - We have been investigating the synergistic cytotoxic interactions between
      tamoxifen (TAM) and cisplatin (DDP) in human malignant cell lines. Recent data
      have demonstrated that TAM activates phospholipase D, which can increase the
      production of prostaglandin D2. Prostaglandin D2 has been shown to have growth
      inhibitory properties in several malignant cell lines. delta 12-Prostaglandin-J2
      (delta 12-PG J2) is a derivative of prostaglandin D2 that has been shown to have
      similar inhibitory properties. We hypothesized that TAM may increase the
      production of delta 12-PG J2, which in turn may synergize with DDP. To begin our
      investigation of this interaction, we sought to determine if delta 12-PG J2 was
      cytotoxic and synergistic in our melanoma system and then expanded our
      observations to include a wide range of malignant cells. We have demonstrated
      that delta 12-PG J2 is cytotoxic to multiple malignant cell lines including
      melanoma, ovarian, prostate, colon, pancreas, small cell lung cancer, and breast
      cancer lines. The IC50s ranged from 0.70 microM (small cell lung cancer) to 3.30
      microM (DDP-resistant melanoma). Additionally, delta 12-PG J2 exhibited
      synergistic cytotoxicity with both DDP and ionizing radiation. These data suggest
      that delta 12-PG J2 should be further evaluated in an in vivo model to confirm
      activity.

PMID- 8752148
TI  - Elevated soluble Fas (sFas) levels in nonhematopoietic human malignancy.
AB  - Fas is a widely expressed membrane-anchored protein that induces apoptosis.
      Soluble Fas (sFas), generated by alternative mRNA splicing, can antagonize cell
      surface Fas function. We have investigated sFas in 104 cancer patients with
      nonhematopoietic malignancies using a Fas-specific ELISA and immunoprecipitation.
      Our studies demonstrate an elevated 40-42-kDa sFas species in both patient serum
      and tumor explants. These observations provide the first evidence that sFas is
      increased in patients with solid tumors in a manner reflective of disease stage
      and tumor burden and argue that sFas can be synthesized and released both
      systemically and locally within the tumor microenvironment.

PMID- 8752149
TI  - Inactivation of the CDKN2 gene by homozygous deletion and de novo methylation is
      associated with advanced stage esophageal squamous cell carcinoma.
AB  - We examined the genomic status of the CDKN2 gene including de novo methylation of
      5' CpG islands in primary and metastatic tumor samples from 31 patients with
      esophageal squamous cell carcinoma. One somatic frame shift mutation (1 of 31;
      3.2%) was identified by PCR-single strand conformational polymorphism analysis
      and DNA sequencing. Homozygous deletion and de novo methylation of the gene were
      confirmed in 5 (16%) and 6 (19%) of 31 patients, respectively. Homozygous
      deletion and de novo methylation were significantly associated with silencing of
      gene expression (P < 0.01). Aberrations of the CDKN2 gene were detected in tumors
      with lymph node metastasis and muscular invasion (12 of 22; 54%) and in none of
      stage I tumors (0 of 9.0%; P < 0.05). These results suggest that homozygous
      deletion and de novo methylation are predominant mechanisms of inactivation of
      the CDKN2 gene and may be associated with metastatic and invasive phenotypes of
      esophageal squamous cell carcinoma.

PMID- 8752150
TI  - bfl-1, a bcl-2 homologue, suppresses p53-induced apoptosis and exhibits potent
      cooperative transforming activity.
AB  - The bcl-2 family of genes code for proteins that contain anti-apoptotic or pro
      apoptotic activity. The human bfl-1 gene contains an open reading frame for a 175
      amino acid Bcl-2 family protein. Among the various Bcl-2 family members, the Bfl
      1 protein shares the highest homology with the mouse A1 protein. These two
      proteins share three conserved domains, Bcl homology (BH)1, BH2, and BH3, with
      other Bcl-2 family proteins. Unlike other Bcl-2 family members, Bfl-1 contains a
      GIn-rich NH2-terminal region and lacks an NH (19K homology) domain 1. We
      demonstrate that the Bfl-1 protein suppresses apoptosis induced by the p53 tumor
      suppressor protein in a manner similar to other Bcl-2 family members such as Bcl
      2, Bcl-xL and EBV-BHRF1. In addition, the bfl-I gene cooperates efficiently with
      the Ela oncogene in transformation of primary rodent epithelial cells. Our
      results suggest that the human bfl-1 gene may play an important role in
      carcinogenesis.

PMID- 8752151
TI  - Type of estrogen receptor determines response to antiestrogen therapy.
AB  - Failure of tamoxifen treatment for unresectable hepatocellular carcinomas (HCCs)
      might be caused by variant estrogen receptors (ERs) in some of these tumors. We
      therefore planned a study in which antihormonal therapy was done with 80 mg/day
      tamoxifen or 160 mg/day megestrol according to the presence of wild-type or exon
      5-deleted variant ER transcripts. Growth rate (evaluated by MRI) of HCCs
      characterized by variant ER transcripts was 4 times more rapid than that of HCCs
      with wild-type ERs. Tumor volume in all patients with wild-type ERs was halved
      after 9 months of tamoxifen treatment, whereas megestrol in patients with variant
      ERs only slowed down tumor growth. Choosing antihormonal treatment according to
      the presence of wild-type or variant ERs in the tumor definitely improves the
      response rate to tamoxifen; in patients with tumors bearing variant ERs,
      megestrol causes only a temporary inhibition of tumor growth.

PMID- 8752152
TI  - Two distinct amplified regions at 17q11-q21 involved in human primary breast
      cancer.
AB  - Chromosomal segment 17q11-q21 is a commonly amplified region in human breast
      carcinomas. Several lines of evidence suggest that ERBB2 is the gene responsible
      for the emergence of this amplicon, but four novel genes (called MLN 50, MLN 51,
      MLN 62, and MLN 64) in 17q11-q21 have recently been found to be amplified and
      overexpressed in breast cancer cell lines. We investigated 98 primary breast
      tumors for amplification of these five loci. Twenty-five tumors (25.5%) showed
      amplification of at least one of these markers, but most amplifications did not
      encompass all of the tested loci. The genes most frequently amplified were ERBB2
      and MLN 64 (22 of 25 amplified cases). MLN 64 was always coamplified with ERBB2,
      and to a similar level. Amplification of these five genes always leads to
      overexpression of their mRNA; we observed no cases of overexpression without
      amplification in any of these genes. Our results suggest that: (a) an
      independent, amplified region defined by MLN 62 (also called CART1 or TRAF4) is
      located in 17q11-q12; (b) in addition to ERBB2, MLN 64 is a major target for the
      17q12-q21 amplicon; and (c) these MLN genes could be of pathogenetic significance
      in breast cancer.

PMID- 8752153
TI  - Regulation of vascular endothelial growth factor expression in human colon
      carcinoma cells by cell density.
AB  - To determine the effect of cell density on vascular endothelial growth factor
      (VEGF) expression and the mechanism of this effect, four human colon cancer cell
      lines were grown as sparse or confluent monolayers or as spheroids. VEGF mRNA
      increased > 2-fold in cells grown as confluent monolayers or spheroids compared
      with cells grown as sparse monolayers. Semiquantitative reverse transcription-PCR
      demonstrated a 2-fold increase in the larger VEGF mRNA isoform (189 bp) in
      confluent cells. Sparse cells grown in conditioned medium from confluent cells
      demonstrated a > 2-fold increase in VEGF mRNA. These data suggest that VEGF
      expression may be regulated by an unidentified soluble factor.

PMID- 8752154
TI  - Rapamycin inhibits constitutive p70s6k phosphorylation, cell proliferation, and
      colony formation in small cell lung cancer cells.
AB  - The serine/threonine kinase p70s6k was found to be constitutively phosphorylated
      in H 69, H 345, and H 510 small cell lung cancer cells as judged by the retarded
      electrophoretic mobility of both isoforms of this kinase. Pretreatment of H 69, H
      345, and H 510 cells with the potent immunosuppressant rapamycin led to p70s6k
      dephosphorylation in a concentration-dependent manner; half-maximum and maximum
      effects were achieved at 0.3 and 3 nM rapamycin, respectively. Rapamycin
      inhibited growth of H 69, H 345, and H 510 cells in liquid culture at similar
      concentrations to those required for inducing dephosphorylation of p70s6k.
      Furthermore, rapamycin markedly reduced the basal colony forming ability of H 69,
      H 345, and H 510 cells in semisolid media. Thus, constitutively
      phosphorylated/active p70s6k plays an important role in promoting the growth of
      small cell lung cancer cells. Furthermore, the rapamycin-sensitive p70s6k pathway
      may provide a novel target for therapeutic intervention in small cell lung
      cancer.

PMID- 8752155
TI  - Antisense epidermal growth factor receptor transfection impairs the proliferative
      ability of human rhabdomyosarcoma cells.
AB  - Human rhabdomyosarcoma cells express membrane epidermal growth factor receptor
      (ECF-R), which could confer responsiveness to EGF and transforming growth factor
      alpha (TGF-alpha) of autocrine or paracrine origin. To study the role played by
      this growth factor circuit in the proliferation and differentiation of myogenic
      neoplastic cells, human rhabdomyosarcoma EGF-R-expressing cells (RD/18 clone)
      have been transfected with a plasmid containing a fragment of the EGF-R cDNA in
      the antisense orientation. In vitro growth and differentiative ability were
      studied on six antisense-transfected clones (AS) in comparison to parental RD/18
      cells and to cells transfected with the plasmid containing only the neomycin
      resistance gene (NEO). A reduced EGF-R membrane expression was found in AS clones
      by decreased immunofluorescence with an anti-EGF-R monoclonal antibody. All AS
      transfectants had a greatly impaired proliferative ability, even when cultured in
      fetal bovine serum-containing medium. Proliferation of AS clones was completely
      blocked in medium supplemented with 2% horse serum. The differentiation ability
      of AS clones was heterogeneous, ranging from clones with a percentage of myosin
      positive cells higher than controls to clones with a negligible myosin
      expression. Therefore, the growth impairment determined by the loop interruption
      is not sufficient to switch on the differentiation program. The role played by
      EGF-R in the proliferation of human rhabdomyosarcoma cells suggests that this
      receptor could constitute a target for a therapeutic approach.

PMID- 8752156
TI  - 2B1 antigen characteristically expressed on extracellular matrices of human
      malignant tumors is a large chondroitin sulfate proteoglycan, PG-M/versican.
AB  - 2B1 is a monoclonal antibody against a large proteoglycan isolated from human
      yolk sac tumor (M. Sobue et al., Histochem. J., 21: 455-460, 1989). The antigen
      is expressed in a variety of embryonal tissues as well as most if not all
      malignant tumor tissues. However, the expression in normal adult tissues is
      limited to some tissues, such as the smooth muscle layers of the aorta. We
      characterized the 2B1 antigen isolated from the conditioned medium of human
      malignant fibrous histiocytoma and found that immunological and biochemical
      properties are identical to those of a large chondroitin sulfate proteoglycan, PG
      M/versican. Partial amino acid sequences of peptides obtained from the core
      protein by V8 protease digestion and subsequent SDS-PAGE were detected in the
      reported amino acid sequence of human PG-M/versican with a complete identity.
      Furthermore, 2B1 was distinctly reactive to the expressed protein by transfection
      of the cDNA for the shortest form into mouse cells. The results indicate that the
      antigen is the PG-M core protein, and the epitope may be in one of the globular
      domains. It is thus likely that PG-M/versican is one of the extracellular matrix
      components characteristic of human malignant tumors.

PMID- 8752157
TI  - Protease inhibitors induce specific changes in protein tyrosine phosphorylation
      that correlate with inhibition of apoptosis in myeloid cells.
AB  - To investigate early signaling events responsible for regulation of programmed
      cell death or apoptosis, we studied campothecin (a topoisomerase I inhibitor)
      mediated apoptosis in the human promyelocytic leukemia cell line HL60. We
      demonstrate a tight correlation between protection of HL60 cells from apoptosis
      associated internucleosomal DNA fragmentation by specific protease inhibitors or
      protein phosphatase inhibitors, with early tyrosine phosphorylation of a single
      protein substrate with a molecular weight of approximately 42,000. Exposure to
      protease inhibitors that did not protect HL60 cells from DNA fragmentation did
      not result in phosphorylation of this substrate. Likewise, a protein tyrosine
      kinase inhibitor that did not interfere with specific phosphorylation did not
      prevent DNA fragmentation. Taken together, these results suggest that
      phosphorylation of a Mr 42,000 substrate constitutes an important signaling event
      that may participate in regulation of the apoptotic response.

PMID- 8752158
TI  - Combined analysis of inherited polymorphisms in arylamine N-acetyltransferase 2,
      glutathione S-transferases M1 and T1, microsomal epoxide hydrolase, and
      cytochrome P450 enzymes as modulators of bladder cancer risk.
AB  - Foreign compound-metabolizing enzymes may modify the risk of chemically induced
      cancer. We wanted to examine enzymes with putative relevance in urinary bladder
      cancer using molecular genetic analyses of heritably polymorphic enzymes.
      Arylamine N-acetyltransferase (NAT2); glutathione S-transferases (GSTs) M1 and
      T1; microsomal epoxide hydrolase; and cytochrome P-450 enzymes (CYP) 1A1, 2C19,
      2D6, and 2E1 were analyzed in 374 cases and in 373 controls in a hospital-based
      case-control study in Berlin. Slow acetylation was a significant risk factor in
      heavy smokers [odds ratio (OR), 2.7; 95% confidence interval (CI), 1.0-7.4], with
      the greatest risk noted for the allele NAT2*5B. GSTM1 deficiency was a risk
      factor independent of smoking and occupation (OR, 1.6; CI, 1.2-2.2). GSTT1 was
      associated with cancer risk in the nonsmoker subgroup (OR, 2.6; CI, 1.1-6.0). The
      two amino acid polymorphisms that are known in microsomal epoxide hydrolase were
      not associated with bladder cancer risk. CYP2D6 activity was rejected as a risk
      factor by phenotyping and by detailed molecular genetic analyses. CYP2C19 may
      have a role in bladder cancer risk, but polymorphisms in CYP1A1 and 2E1 had no
      statistically significant impact. Deficiencies in both NAT2 and GSTM1 failed to
      show significant synergistic or antagonistic interactions. In conclusion,
      molecular genetic analysis of a large sample specified the increased bladder
      cancer risk of those who are deficient in NAT2 and GSTM1; the other traits proved
      to be of minor impact.

PMID- 8752160
TI  - TuAg.1 is the liver isoform of the rat colon tumor-associated antigen pE4 and a
      member of the immunoglobulin-like supergene family.
AB  - TuAg.1 is a tumor-associated membrane glycoprotein first identified in rat
      hepatocellular carcinoma by monoclonal antibodies (mAbs) 324.5 and 324.9. This
      oncofetal antigen is also expressed by hepatocytes in cell culture but not normal
      adult hepatocytes in vivo. Affinity chromatography and preparative continuous
      elution slab-gel electrophoresis were used to separate TuAg.1 from co-purified
      actin and immunoglobulin. TuAg.1 was recovered as a series of bands Mr 82,000
      90,000, which were pooled and subjected to CNBr digestion for primary amino acid
      sequence analysis. Computer database analysis of TuAg.1 peptide sequence revealed
      homology to the rat colon carcinoma-associated antigen pE4, a member of the
      immunoglobulin gene superfamily. Oligonucleotide primers derived from sequences
      shared by TuAg.1 and pE4 were used in reverse transcription-PCR to amplify tumor
      specific products corresponding to TuAg.1 cDNA. Northern blot analysis with one
      of these products confirmed the oncofetal expression of transcripts related to
      TuAg.1/pE4 and indicated an RNA species of different size expressed only in
      normal liver. Identity between TuAg.1 and pE4 was further confirmed by
      immunochemical analysis with mAb 324.5 and mAb E4. Both antibodies were reactive
      with the same protein on transplantable hepatocellular carcinoma AS30D but
      recognized different epitopes. The reactivity of human tumor cells with mAb 324.5
      and 324.9 indicates the presence of a related TuAg.1 molecule expressed in human
      neoplasia as well.

PMID- 8752159
TI  - Characterization of purified human recombinant cytochrome P4501A1-Ile462 and 
      Val462: assessment of a role for the rare allele in carcinogenesis.
AB  - Human cytochrome P4501A1 (CYP1A1) occurs extrahepatically and is polymorphic, the
      common form having Ile at position 462 and the rare form having Val. The rare
      allele has been associated with enhanced susceptibility to lung cancer. To
      resolve its role in cancer we have constructed CYP1A1-Val462 cDNA by site
      directed mutagenesis from CYP1A1-Ile462, as confirmed by sequencing and allele
      specific PCR. Both alleles were expressed in Escherichia coli, and CYP1A1-Ile462
      and -Val462 were purified to electrophoretic homogeneity. The secondary
      structures of both forms were virtually identical, with high alpha helix content,
      as assessed by circular dichroism. The P450s stereoselectively and
      regioselectively catalyzed the metabolism of (R)- and (S)- warfarin, in
      reconstituted systems, with very similar profiles. Both P450s produced (R)-6- and
      8-hydroxy-warfarin with Km values of 0.40 +/- 0.06 and 0.43 +/- 0.05 mM,
      respectively, and Vmax values of 84.0 +/- 6.8 and 137.7 +/- 8.9 pmol/min/nmol
      CYP1A1-Val462, respectively, 1.0 +/- 0.1 and 1.0 +/- 0.1 mM, respectively, and
      46.7 +/- 2.5 and 80.0 +/- 4.4 pmol/min/nmol CYP1A1-Ile462, respectively.
      Reconstituted CYP1A1-Val462 catalyzed ethoxyresorufin metabolism at a slightly
      but significantly higher rate than did CYP1A1-Ile462; Vmax values were 4.4 +/-
      0.6 and 3.1 +/- 0.3 nmol/min/nmol CYP1A1, respectively. However, with the
      carcinogen benzo(a) pyrene as substrate, reconstituted CYP1A1-Ile462 together
      with epoxide hydrolase produced 7,8- and 9,10-dihydrodiols at comparable rates
      than did CYP1A1-Val462. Thus, the apparently greater susceptibility of the CYP1A1
      Val462 genotype to lung cancer is probably not related to greater extents of
      carcinogen bioactivation.

PMID- 8752161
TI  - Human N-acetylation of benzidine: role of NAT1 and NAT2.
AB  - These studies were designed to assess metabolism of benzidine and N
      acetylbenzidine by N-acetyltransferase (NAT) NAT1 and NAT2. Metabolism was
      assessed using human recombinant NAT1 and NAT2 and human liver slices. For
      benzidine and N-acetylbenzidine, Km and Vmax values were higher for NAT1 than for
      NAT2. The clearance ratios (NAT1/NAT2) for benzidine and N-acetylbenzidine were
      54 and 535, respectively, suggesting that N-acetylbenzidine is a preferred
      substrate for NAT1. The much higher NAT1 and NAT2 Km values for N-acetylbenzidine
      (1380 +/- 90 and 471 +/- 23 microM, respectively) compared to benzidine (254 +/-
      38 and 33.3 +/- 1.5 microM, respectively) appear to favor benzidine metabolism
      over N-acetylbenzidine for low exposures. Determination of these kinetic
      parameters over a 20-fold range of acetyl-CoA concentrations demonstrated that
      NAT1 and NAT2 catalyzed N-acetylation of benzidine by a binary ping-pong
      mechanism. In vitro enzymatic data were correlated to intact liver tissue
      metabolism using human liver slices. Samples incubated with either [3H]benzidine
      or [3H]N-acetylbenzidine had a similar ratio of N-acetylated benzidines (N
      acetylbenzidine + N',N'-diacetylbenzidine/ benzidine) and produced amounts of N
      acetylbenzidine > benzidine > N,N'-diacetylbenzidine. With [3H]benzidine, p
      aminobenzoic acid, a NAT1-specific substrate, increased the amount of benzidine
      and decreased the amount of N-acetylbenzidine produced, resulting in a decreased
      ratio of acetylated products. This is consistent with benzidine being a NAT1
      substrate. N-Acetylation of benzidine or N-acetylbenzidine by human liver slices
      did not correlate with the NAT2 genotype. However, a higher average acetylation
      ratio was observed in human liver slices possessing the NAT1*10 compared to the
      NAT1*4 allele. Thus, a combination of human recombinant NAT and liver slice
      experiments has demonstrated that benzidine and N-acetylbenzidine are both
      preferred substrates for NAT1. These results also suggest that NAT1 may exhibit a
      polymorphic expression in human liver.

PMID- 8752162
TI  - Effects of hyperthermic isolated limb perfusion with recombinant tumor necrosis
      factor alpha and melphalan on the human fibrinolytic system.
AB  - This study was undertaken to determine the effects on systemic fibrinolysis of
      hyperthermic isolated limb perfusion with recombinant tumor necrosis factor alpha
      (r-TNF-alpha) and melphalan, with or without pretreatment with recombinant IFN
      gamma (r-IFN-gamma). Twenty patients were treated with r-TNF-alpha and melphalan;
      four patients, treated with melphalan only, served as controls. Of the twenty
      patients treated with both r-TNF-alpha and melphalan, eight received r-IFN-gamma
      for two days before the perfusion and as a bolus into the perfusion circuit. A
      significant leak of r-TNF-alpha from the perfusion circuit to the systemic
      circulation was observed in all r-TNF-alpha-treated patients (mean maximum TNF
      alpha, 87,227 ng/liter versus 31 ng/liter in controls; P < 0.002). In these
      patients, but not in controls, there was an almost instantaneous rise in systemic
      tissue plasminogen activator activity (from 0.26 to 5.28 IU/ml in 90 min),
      causing activation of fibrinolysis. After a delay of 90 min, plasminogen
      activator inhibitor-1 (PAI-1) antigen rose to high levels in the r-TNF-alpha
      treated group (mean maximum PAI-1, 1652 ng/ml versus 211 ng/ml in controls; P <
      0.02), associated with a sharp decrease of tissue plasminogen activator activity
      and a slower decrease of plasminogen-antiplasminogen complexes (from 5.28 to 0.02
      IU/ml in 2 h and from 1573 to 347 micrograms/liter in 22 h, respectively). No
      additional effect of IFN-gamma pretreatment on fibrinolysis could be
      demonstrated. These results suggest that in isolated limb perfusion with r-TNF
      alpha and melphalan an initial activation of systemic fibrinolysis, induced by
      leakage of r-TNF-alpha from the perfusion circuit, is set off by a subsequent
      inhibition of the fibrinolytic system by PAI-1. This large increase in PAI-1
      could place the patient at risk for deposition of microthrombi in the systemic
      circulation.

PMID- 8752163
TI  - Uterine expression of vascular endothelial growth factor is increased by
      estradiol and tamoxifen.
AB  - Vascular endothelial growth factor (VEGF) is an endothelial-specific mitogen with
      potent angiogenic activity. Because vascular growth accompanies normal
      endometrial regeneration and may also be involved in uterine tumor growth, we
      studied VEGF regulation by 17 beta-estradiol (E2) and tamoxifen, two agents that
      can increase uterine cell proliferation and tumor incidence. In immature,
      ovariectomized rats, E2 elevates uterine VEGF mRNA transiently, with a peak
      induction of 15-20-fold within 1 h. A maximum response is produced at a dose of 4
      micrograms/kg E2, and induction is specific for estrogenic steroids. E2-dependent
      VEGF induction is inhibited by actinomycin D but not puromycin, suggesting that
      the effect is due at least in part to direct estrogen receptor regulation of VEGF
      transcription. PCR amplification and DNA sequencing indicated that VEGF188,
      VEGF164, and VEGF120 are all induced by E2, but the latter two are the
      predominant forms in the uterus. In situ hybridization shows a predominantly
      stromal expression of VEGF mRNA. The antiestrogens tamoxifen, 4-OH tamoxifen, and
      nafoxidine produce similar increases in uterine VEGF mRNA levels within 6 h, with
      1 mg/kg tamoxifen producing a maximum response of 15-20-fold. The tamoxifen
      response was also inhibited by actinomycin D but not by puromycin, again
      suggesting direct transcriptional regulation of VEGF expression by antiestrogens.
      These findings raise the possibility that estrogen and antiestrogen effects on
      uterine edema, proliferation, and tumor incidence may involve local increases in
      tissue VEGF production.

PMID- 8752164
TI  - Homozygous rapid arylamine N-acetyltransferase (NAT2) genotype as a
      susceptibility factor for lung cancer.
AB  - The polymorphic arylamine N-acetyltransferase (NAT2) is supposed to be a
      susceptibility factor for certain malignancies. A phenotyping study in 389 lung
      cancer patients revealed a similar distribution of rapid and slow acetylators by
      the caffeine test to that in 657 reference subjects (odds ratio, 1.05; 95%
      confidence limits, 0.81, 1.36; not significant). A separate group of 155 lung
      cancer patients was studied by genotyping NAT2 and was compared with a matched
      reference group of 310 unrelated patients and with 278 healthy volunteers. The
      NAT2 genotype was characterized by PCR-RFLP at nucleotide positions 191, 282,
      341, 481, 590, 803, and 857. For evaluation of nucleotide 341, a 3'-mismatch
      primer was used. Homozygous wild-type genotypes NAT2*4/*4 were confirmed by DNA
      sequencing. Genotypes for rapid acetylation amounted to 43.9% among lung cancer
      and 41.6% among reference patients (odds ratio, 1.10 95% confidence limits, 0.73,
      1.65; not significant). Discrimination into homozygous and heterozygous carriers
      of allele NAT2*4 revealed a distinct over-representation of NAT2*4/*4 genotypes
      amid lung cancer patients (odds ratio, 2.36; 95% confidence limits, 1.05, 5.32; P
      = 0.018). Logistic regression analysis considering sex, age, and smoking provided
      an odds ratio of 3.04 (95% confidence limits, 1.37, 6.75; P = 0.003). Hence,
      carriers of the NAT2*4/*4 genotype, with its especially high acetylation
      capacity, are at significantly increased risk to lung cancer.

PMID- 8752166
TI  - Benzo(a)pyrene diol epoxide-induced chromosomal aberrations and risk of lung
      cancer.
AB  - Benzo(a)pyrene is considered a classic DNA-damaging carcinogen and is one of a
      multitude of polycyclic aromatic hydrocarbons commonly found in tobacco smoke and
      in the ambient environment. In this report, we describe the characteristics of
      chromosomal aberrations induced in vitro by activated benzo(a)pyrene diol epoxide
      (BPDE) in lymphocyte cultures of 172 normal individuals ages 19-95 years and
      present the analysis of a pilot case-control study of 33 lung cancer patients and
      96 selected controls without history of cancer and frequency matched on age (50
      85 years) to the cases. The BPDE-induced chromosomal aberrations were
      predominantly single chromatid breaks, with few isochromatid breaks or exchange
      figures. In the 172 normal subjects, the frequencies of both spontaneous and BPDE
      induced chromatid breaks were not correlated with age, sex, ethnicity, or tobacco
      use. However, the frequency of BPDE-induced chromatid breaks was significantly
      correlated with the frequency of spontaneous chromatid breaks (r = 0.19, P <
      0.05). In addition, Hispanics had significantly higher mean BPDE-induced
      chromatid breaks than did non-Hispanic whites (P < 0.01). From the case-control
      analyses, the frequency of BPDE-induced chromosomal aberrations was significantly
      higher in cases (mean, 0.67 breaks/cell) than in controls (mean, 0.41
      breaks/cell; P < 0.0001). An adjusted odds ratio of 6.53 (95% confidence
      interval, 3.74-11.4) for lung cancer was associated with increased frequency of
      these chromosomal aberrations. The higher rate of BPDE-induced chromosomal
      aberrations may be due to inefficient DNA repair. These findings warrant
      additional molecular epidemiological studies. The BPDE mutagen sensitivity assay
      will facilitate epidemiological studies of genetic susceptibility to smoking
      related cancers.

PMID- 8752165
TI  - Interleukin 2 production in vitro by peripheral lymphocytes in response to human
      papillomavirus-derived peptides: correlation with cervical pathology.
AB  - Human papillomavirus (HPV) is believed to be the major cause of cervical cancer.
      To investigate whether a cellular immune response, especially a T helper type 1
      response, is related to the natural defense against HPV-related cervical lesions,
      the interleukin 2 response of peripheral blood lymphocytes in vitro to
      overlapping peptides from HPV-16 E6 and E7 oncoproteins was compared with the
      degree of cervical cytological abnormality among 140 women in a cross-sectional
      study. We compared 66 women diagnosed with low-grade squamous intraepithelial
      lesions (LSIL), 21 with high-grade squamous intraepithelial lesions (HSIL), and
      28 with invasive cervical cancer with 25 women who were cytologically normal but
      previously HPV-16 DNA positive. The fraction showing strong interleukin 2
      production against HPV-16 peptides was greatest among cytologically normal women
      (35%) and declined with increasing disease severity [LSIL] (20%), HSIL, (17%),
      and cancer patients (7%); X2 test P for the trend = 0.02], whereas the responses
      against a recall influenza antigen were not significantly different among groups.
      Our finding suggests that a T helper lymphocyte type 1 response to HPV antigens
      is associated with disease status. This result may reflect a targeted effect of
      the disease on immune function or a protective effect of the immune response
      against disease progression.

PMID- 8752167
TI  - Combination chemotherapy and photodynamic therapy with N-(2-hydroxypropyl)
      methacrylamide copolymer-bound anticancer drugs inhibit human ovarian carcinoma
      heterotransplanted in nude mice.
AB  - This study characterizes the efficacy and toxicity of: (a) free Adriamycin and N
      (2-hydroxypropyl) methacrylamide (HPMA) copolymer-Adriamycin conjugate (P-A); (b)
      free and HPMA copolymer-meso-chlorin e6 monoethylene diamine disodium salt (Mce6)
      conjugate (P-C) and light-induced photodynamic therapy; and (c) combinations of
      the HPMA copolymer conjugates (P-A and P-C) in the destruction of human
      epithelial ovarian carcinoma heterotransplanted in the nude mouse (OVCAR-3).
      Eight-week-old female nu/nu mice were injected in both flanks with 0.04-0.05 cm3
      OVCAR-3 solid tumor dispersed in media. When bilateral tumors reached a minimum
      volume of 0.18 cm3 (one axis, 2.0-mm minimum) and demonstrated consistent growth,
      the experiments were initiated. Drugs were given i.v. unless otherwise noted.
      Tumor-bearing mice were allocated to the following protocols: (a) Adriamycin at 1
      mg/kg, P-A at 30 mg/kg (2.2 mg/kg Adriamycin equivalent), and controls (n = 6
      each); (b) Mce6 and light (2 h after administration: 650 nm light for 15 min to
      deliver 220 J/cm2) at 1.25, 2.5, 5, and 10 mg/kg (n = 6 each), 2.5 mg/kg i.p. (n
      = 4), and controls (n = 6); (c) P-C at 12.5, 25, and 75 mg/kg (1.5, 2.9, and 8.7
      mg/kg Mce6 equivalent, respectively with light (18 h after administration; 650 nm
      light for 15 min to deliver 220 J/cm2), P-C at 25 mg/kg (2.9 mg/kg Mce6
      equivalent) with no light administration, and controls (n = 7 each); and (d) a
      combination of P-A (30 mg/kg, 2.2 mg/kg adriamycin equivalent) and P-C (12.5 and
      75 mg/kg, 1.5 mg/kg and 8.7 mg/kg Mce6 equivalent, respectively) with and without
      light (n = 7 each; 18 h after administration; 650 nm light for 15 min to deliver
      220 J/cm2) and controls (n = 12). Tumor volumes and animals weights were assessed
      for significant differences from the treated and controls groups by Student's t
      test. Adriamycin (1 mg/kg) and P-A (30 mg/kg. 2.2 mg/kg Adriamycin equivalent)
      caused less than a 10% weight loss, and treated tumor volumes (day 10-32) were
      significantly less than those of controls (all P < 0.045). Mce6 (2.5-10 mg/kg
      i.v.), caused tumor regression in 80% of tumors and a shock syndrome in 17-83%.
      i.p. dosing (2.5 mg/kg) was uniformly fatal. Mce6 at 1.25 mg/kg did not show
      reproducible efficacy. P-C with light (25 and 75 mg/kg, 2.9 and 8.7 mg/kg Mce6
      equivalent, respectively) demonstrated significant tumor destruction (P < 0.003)
      but not complete ablation. The combinations of P-A (30 mg/kg, 2.2 mg/kg
      Adriamycin equivalent) plus P-C (12.5 and 75 mg/kg; 1.5 mg/kg and 8.7 mg/kg of
      Mce6 equivalent, respectively) with light resulted in tumor volumes that were
      significantly less than control tumor volumes and the tumor volumes of mice
      receiving either P-A (30 mg/kg, 2.2 mg/kg Adriamycin equivalent) or P-C with
      light (12.5 or 75 mg/kg. 1.5 or 8.7 mg/kg Mce6 equivalent, respectively) alone
      (all P < 0.02). P-C (75 mg/kg, 8.7 mg/kg Mce6 equivalent) added to P-A (30 mg/kg,
      2.2 mg/kg Adriamycin equivalent) resulted in complete tumor ablation. Free Mce6
      demonstrates a narrow margin of safety, which is extended by incorporation into
      HPMA copolymers. P-A demonstrates safety and efficacy in vivo. The combined
      chemotherapy and photodynamic therapy of P-A (30 mg/kg, 2.2 mg/kg Adriamycin
      equivalent) with P-C and light (12.5 and 75 mg/kg 1.5 and 8.7 mg/kg Mce6
      equivalent, respectively) was nontoxic and allowed us to attain a significant
      improvement in tumor cures than those obtained by P-A or P-C with light alone.

PMID- 8752168
TI  - Intrathecal chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea encapsulated
      into hybrid liposomes for meningeal gliomatosis: an experimental study.
AB  - 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), one of the chloroethyl nitrosoureas,
      is effective against malignant glioma. To develop its use in intrathecal
      chemotherapy, we encapsulated BCNU in hybrid liposomes composed of
      dimyristoylphosphatidylcholine and micellar surfactants (Tween 20) and dissolved
      it in artificial cerebrospinal fluid (lipo-BCNU). We then studied the toxicity of
      hybrid liposomes and cellular proliferation inhibition of lipo-BCNU in vitro. We
      found that 3 mM hybrid liposomes did not affect the viability of human
      endothelial cells and that lipo-BCNU inhibited the proliferation of human glioma
      cell lines U-105MG, U-251MG, and U-373MG, and rat glioma cell lines C6 and 9L in
      a concentration-dependent fashion. Wistar rats that were administered lipo-BCNU
      intracisternally showed no weight loss, neurological symptoms, or histological
      changes of the brain and spinal cord. A Wistar rat model of meningeal gliomatosis
      was established by intracisternal inoculation of 0.1 ml cell suspension
      containing 1 x 10(6) or 5 x 10(6) viable C6 glioma cells. Two days after
      inoculation, lipo-BCNU (BCNU, 2.5 mg/kg) was administered intracisternally. When
      1 x 10(6) glioma cells were inoculated (experiments 1 and 2), the median survival
      times were 24.5 and 26 days in the control groups and 32 and 45 days in the lipo
      BCNU-treated groups. respectively. When 5 x 10(6) glioma cells were inoculated
      (experiments 3-6), the median survival times were 17-29.5 days in the control
      groups and 23-44 days in the treated groups, respectively. Significantly
      prolonged survival was obtained in three of six experimental groups. After the
      administration of 1 ml lipo-BCNU (BCNU, 4.67 mM) or 1 ml BCNU solubilized with 5%
      dextrose/water (BCNU, 4.67 mM) into the cisterna magna of dogs, the cisterna
      magna cerebrospinal fluid was sampled, and the BCNU concentrations were assayed
      by high-performance liquid chromatography. The half-life of the lipo-BCNU was
      longer than that of BCNU solubilized with 5% dextrose/water. These results
      suggest that the intrathecal administration of lipo-BCNU may be possible for the
      treatment of meningeal gliomatosis.

PMID- 8752169
TI  - Determinants of tamoxifen sensitivity control the nature of the synergistic
      interaction between tamoxifen and cisplatin.
AB  - The cytotoxic effect of tamoxifen (TAM) was investigated in the T-289 melanoma
      cell line, as well as the 289 DDP3 cisplatin (DDP)-resistant and the 289 TAM6 TAM
      resistant variant melanoma cell lines to determine the effect of drug resistance
      on synergy. T-289 melanoma cells were made DDP or TAM resistant through chronic
      exposure to increasing concentrations of the respective drugs. Whereas DDP
      resistance could be overcome by increasing the concentration of TAM, the
      development of TAM resistance completely abolished synergy. TAM resistance was
      not related to the development of estrogen receptors, decreased TAM uptake, or
      the increased expression of the mdr-1 gene. TAM did not inhibit the action of
      Topoisomerase 1; however, TAM did induce apoptosis in the 289 melanoma cells. In
      contrast, TAM did not induce apoptosis in the TAM-resistant variant 289 TAM6
      cells. To our knowledge, these are the first data associating TAM resistance with
      the inhibition of apoptosis.

PMID- 8752170
TI  - Intravenous RMP-7 selectively increases uptake of carboplatin into rat brain
      tumors.
AB  - Rats implanted with RG-2 gliomas were administered i.v. RMP-7 and
      [14C]carboplatin. Changes in the permeability of the blood-brain barrier to
      carboplatin were determined using quantitative autoradiography. i.v. infusions of
      RMP-7 induced an increase in the permeability of the vascular barrier within the
      tumor to carboplatin. Additionally, permeability of brain tissue proximal to, but
      clearly outside the tumor mass, was also increased. Progressively less uptake of
      [14C]carboplatin was observed as distance from the tumor border increased. The
      increases in permeability induced by RMP-7 occurred in a dose-related fashion. No
      increase in carboplatin level was observed in several nonbrain tissues, including
      sciatic nerve, retina, heart, lung, liver, kidney, and spleen. Finally, the
      permeabilizing effects of RMP-7 were shown to occur independent of histaminergic
      or hypotensive mechanisms. These data provide additional insight into the
      permeabilizing effects and mechanism of RMP-7 and offer additional support for
      the therapeutic utility of this novel compound as an adjunctive treatment for
      human gliomas.

PMID- 8752171
TI  - Dual modes of death induced by etoposide in human epithelial tumor cells allow
      Bcl-2 to inhibit apoptosis without affecting clonogenic survival.
AB  - The Bcl-2 oncoprotein, which is expressed in a variety of human malignancies,
      blocks apoptosis induced by chemotherapeutic drugs, including the topoisomerase
      II inhibitor, etoposide. To determine the significance of Bcl-2 in etoposide
      induced death of human epithelial tumor cells, HeLa S3 cells were transfected
      with human bcl-2 cDNA in the pSFFV expression vector, and stable Bcl-2-expressing
      clones established. In agreement with previous studies, Bcl-2 inhibited loss of
      cell viability (by trypan blue exclusion), the appearance of morphologically
      apoptotic cells, and the amount of low molecular weight DNA extracted after
      etoposide exposure (25 microns, 4 h). The degree of inhibition, compared to wild
      type and vector control-transfected clones, differed according to the level of
      Bcl-2 protein expressed in the two clones studied. However, when cell survival
      was assessed by colony-forming assays, no significant differences were detected
      at any of the etoposide concentrations used. Although Bcl-2 inhibited etoposide
      induced apoptosis, it had no effect on the formation of giant, multinucleated
      cells characteristic of mitotic catastrophe. Consequently, the ability of Bcl-2
      to prevent apoptosis caused by chemotherapeutic drugs may not necessarily
      translate into increased survival of cells that express Bcl-2.

PMID- 8752173
TI  - Microsatellite instability correlates with reduced survival and poor disease
      prognosis in breast cancer.
AB  - Size changes in microsatellite sequences have been detected in many types of
      cancer, but the influence of this form of genetic instability on disease
      progression remains unclear. We determined the incidence of microsatellite
      instability in breast cancer by comparing PCR-amplified sequences from paraffin
      embedded samples of normal and tumor tissue from affected individuals. This
      analysis showed that at least 30% of breast cancers exhibit microsatellite
      instability (MI). Of importance, MI correlated with indicators commonly
      associated with poor disease prognosis, including lymph node status, tumor size,
      and advanced tumor stage. Individuals with MI+ tumors also showed significantly
      reduced disease-free and overall survival. These data contrast with studies
      showing that MI correlates with improved prognosis in colon and gastric cancers.
      We propose that defects resulting in MI promote disease progression and result in
      a poor prognosis in breast cancer.

PMID- 8752172
TI  - A soluble insulin-like growth factor I receptor that induces apoptosis of tumor
      cells in vivo and inhibits tumorigenesis.
AB  - By a frame-shift mutation, we have engineered a human IGF-I receptor (IGF-IR)
      cDNA that produces a receptor 486 amino acids long (plus the 30 amino acids of
      the signal peptide). This receptor, which we have designated as 486/STOP, is
      partially secreted into the medium of cells in culture and markedly inhibits the
      autophosphorylation of the endogenous IGF-IRs as well as the activation of the
      signaling pathway. The 486/STOP receptor acts as a strong dominant negative for
      several growth functions: (a) it inhibits the growth of cells in monolayers; (b)
      it inhibits the growth of transformed cells in soft agar; (c) it induces
      extensive apoptosis in vivo; and (d) it inhibits tumorigenesis in syngeneic rats.
      This is the first demonstration that a dominant negative of the IGF-IR can induce
      massive apoptosis of tumor cells in vivo.

PMID- 8752174
TI  - Increased brain tumor microvessel permeability after intracarotid bradykinin
      infusion is mediated by nitric oxide.
AB  - Nitric oxide (NO), a free radical gas implicated in a wide variety of biological
      reactions, is a novel signaling molecule that may regulate vasodilation, cerebral
      blood flow, and vascular permeability. This study was performed to determine
      whether NO mediates the selective increase in brain tumor microvessel
      permeability after intracarotid infusion of bradykinin in the RG2 rat glioma
      model. Intracarotid infusion of bradykinin selectively increased the transport of
      radiolabeled alpha-aminoisobutyric acid and dextran into brain tumors. Transport
      into normal brain was not increased. The administration of an NO synthase
      inhibitor, NG-nitro-L-arginine methyl ester, significantly inhibited the
      increased transport into tumors for both tracers. The inhibitory effect of NG
      nitro-L-arginine methyl ester on the response to bradykinin was reversed by L
      arginine. The expression of two NO synthase (NOS) isoforms in cultured RG2 glioma
      cell lines and intracerebral RG2 glioma was examined by immunohistochemistry and
      Western blot analysis. High levels of expression of neuronal NOS were detected in
      cultured and intracerebral RG2 cells but not in normal brain tissue, except in
      rare neuronal cells. The endothelial form of NOS was also expressed in cultured
      RG2 cells, but not as strongly as neuronal NOS expression. In intracerebral RG2
      gliomas, expression of endothelial NOS in the tumor was detected at higher levels
      than in normal brain. These findings indicate that RG2 rat gliomas express high
      levels of NOS, which regulate the production of NO, compared with normal brain.
      We suggest that the selective permeability increase in brain tumor microvessels
      after bradykinin infusion is mediated by NO. Furthermore, the absence of high
      levels of NOS in normal brain may account for the attenuated permeability
      response to bradykinin in normal brain microvessels.

PMID- 8752175
TI  - Complete inhibition of angiogenesis and growth of microtumors by anti-vascular
      endothelial growth factor neutralizing antibody: novel concepts of angiostatic
      therapy from intravital videomicroscopy.
AB  - In the present study, we evaluated the effects of a neutralizing antivascular
      endothelial growth factor (anti-VEGF) antibody on angiogenesis and growth of
      tumor spheroids using an intravital microscopic technique permitting noninvasive,
      in vivo and in situ study of tumor angiogenesis and tumor growth in conscious
      mice. Tumor spheroids of the human rhabdomyosarcoma cell line A673, with a
      diameter between 600 and 1000 microns, were implanted in dorsal skinfold chambers
      inserted on Beige nude/xid mice. Tumor cells were prelabeled with a fluorescent
      vital dye [(5-(and-6)-((4-chloromethyl)benzoyl)amino)tetramethylrhodamine], which
      allowed estimation of the growth of the implanted tumor spheroids. Treatment
      (i.p.) with the monoclonal antibody A4.6.1, specific for VEGF, completely
      inhibited neovascularization of the microtumors and suppressed their growth to
      the extent that tumors implanted in treated animals leveled off at a volume less
      than 1 mm3, i.e., the anti-VEGF antibody dramatically changed the growth
      characteristics of the tumor line from being a rapidly growing malignancy to a
      dormant microcolony.

PMID- 8752176
TI  - An experimental model of bone metastasis by human lung cancer cells: the role of
      parathyroid hormone-related protein in bone metastasis.
AB  - In the formation of bone metastasis, osteoclastic bone resorption is necessary
      before the expansion of tumor cells from bone marrow to bone, and several
      cytokines, which possess osteoclast-stimulating activity, could be involved in
      this step. In this paper, we describe a bone metastasis model in nude mice using
      human lung squamous cell carcinoma-derived cells (HARA), in which the parathyroid
      hormone-related protein (PTHrP) gene, one of the most potent osteoclast
      activating factors, is strongly expressed. The injection of HARA cells (1 x
      10(5)) into the left cardiac ventricle resulted in tumor colonies exclusively in
      the skeletal system at 4 and/or 8 weeks after inoculation. An anti-PTHrP antibody
      injected via a tail vein reduced the incidence of bone metastases, number of
      tumor colonies, and tumor volume after the inoculation of HARA cells. The
      injection of another line of human lung squamous cell carcinoma-derived cells (QG
      56), in which the PTHrP gene is not expressed, resulted in no bone metastasis.
      These findings suggest that PTHrP plays an important role in the formation of
      bone metastasis.

PMID- 8752177
TI  - Inhibition of hamster mesothelioma tumorigenesis by an antisense expression
      plasmid to the insulin-like growth factor-1 receptor.
AB  - We evaluated the effect of antisense insulin-like growth factor (IGF) receptor
      transcripts on the proliferation and tumorigenicity in an SV40-induced,
      immunocompetent hamster mesothelioma model (H9A). Expression of IGF-1 and IGF-1
      receptor (IGF-1R) genes was identified from H9A RNA using reverse transcription
      PCR and Northern analysis. H9A cells were electroporated with inducible
      expression vectors (under the transcriptional control of heat shock promoter
      HSP70) containing a cDNA fragment corresponding to base pairs 1-309 of IGF-1R in
      the sense or antisense orientation to generate the respective clones A3 sense or
      B9 antisense. The expression vector in genomic DNA was detected with PCR analysis
      as a 173-bp fragment on ethidium bromide gels. The effects of the expression
      vectors were then evaluated in vitro under active (at 39 degrees C) or inactive
      (at 34 degrees C) conditions. At 39 degrees C, the B9 antisense transfectants
      demonstrated significantly less proliferation than A3 sense transfectants (P2 <
      0.02). At 34 degrees C, cell growth of A3 sense- and B9 antisense-transfected
      cells was not significantly different. In vivo tumorigenicity was evaluated in
      hamsters inoculated with 10(5) A3 sense- or B9 antisense-transfected cells. The
      A3 sense clones resulted in greater numbers of tumors in vivo compared to the B9
      antisense clone (P2 = 0.0001). When genomic DNA from tumors that developed in A3
      sense and B9 antisense animals was analyzed for the expression vectors, a 173-bp
      fragment amplified from the expression vector was identified in the sense tumors
      but not in antisense B9 or wild-type H9A tumors, indicating a loss of the vector
      from the antisense clones that proliferated in vivo. The inhibitory effect of IGF
      1R antisense transcripts on hamster mesothelioma demonstrated in this study by
      decreased growth and tumorigenicity in vitro and in vivo may have implications
      for the therapy of human mesothelioma.

PMID- 8752178
TI  - Presence of an insulin-like growth factor I autocrine loop predicts uterine
      fibroid responsiveness to tamoxifen.
AB  - Uterine leiomyoma is an estrogen-responsive tumor, and the present studies
      examine the ability of the antiestrogen tamoxifen to modulate leiomyoma cell
      growth. Tamoxifen is an effective form of hormonal therapy for breast cancer,
      although the mechanism by which tamoxifen inhibits tumor growth is not well
      understood and may involve mechanisms other than the action of tamoxifen as an
      estrogen antagonist. Tamoxifen was found to inhibit the proliferation of three of
      five leiomyoma-derived cell lines (ELT cell lines) in vitro, including an
      estrogen receptor-negative cell line. The ability of tamoxifen to decrease
      leiomyoma growth was found to correlate with expression of insulin-like growth
      factor I (IGF-I) by the tumor cells, suggesting that the inhibitory effects of
      tamoxifen were associated with expression of this growth factor. The existence of
      an IGF-I autocrine loop in the cells was investigated, because transcripts for
      both IGF-I and its cognate receptor were expressed in the tamoxifen-responsive
      cell lines. An IGF-I RIA demonstrated secreted IGF-I protein in serum-free medium
      conditioned by the IGF-I-expressing cell line ELT 3, and this same medium
      supported the growth of IGF-requiring MCF-10A cells, indicating the presence of
      biologically active IGF-I in the conditioned medium. Exogenous IGF-I stimulated
      ELT 3 cell proliferation, confirming that this growth factor is mitogenic for
      leiomyoma cells. IGF-I neutralizing antibody inhibited ELT 3 growth, indicating
      that the levels of IGF-I produced by the leiomyoma cells were physiologically
      significant. These data demonstrate the existence of an IGF-I autocrine loop in
      tamoxifen-sensitive leiomyoma cells, supporting the hypothesis that the presence
      of an IGF-I autocrine loop predicts uterine fibroid responsiveness to tamoxifen.

PMID- 8752179
TI  - Parathyroid hormone-related protein gene expression in human squamous carcinoma
      cells is repressed by mutant isoforms of p53.
AB  - Parathyroid hormone-related protein (PTHrP) is a normal secretory product of a
      variety of squamous epithelia, including epidermal keratinocytes. Only a subset
      of squamous carcinomas, however, express the gene at levels sufficient to cause
      humoral hypercalcemia. In the present study, comparison of PTHrP expression
      levels with p53 functional status in a series of squamous carcinoma lines has
      revealed an association between expression of specific mutant isoforms of p53 and
      very low levels of PTHrP mRNA. Evaluation of p53 isoforms with mutations in
      codons 248 and 273 showed them to be capable of repressing PTHrP gene expression
      in a high-expressing, p53-negative squamous line by approximately 50%.
      Conversely, inactivation of an endogenous mutant p53 with E1B proteins resulted
      in an increase in PTHrP expression in a low-expressing cell line. Subsequent
      analysis of promoter-specific PTHrP transcripts in a p53-negative squamous line
      transfected with mutant p53 isoforms suggested that down-regulation occurred
      primarily at the two TATA-based promoters. Direct testing of a murine PTHrP
      reporter construct in transient transfection assays confirmed the capacity of the
      248 and 273 mutants to repress this TATA-based promoter, although only about half
      as effectively as wild-type p53.

PMID- 8752180
TI  - E-cadherin expression in human breast cancer cells suppresses the development of
      osteolytic bone metastases in an experimental metastasis model.
AB  - The molecular mechanisms by which human cancer cells spread to bone are largely
      unexplored. The process likely involves cell adhesion molecules (CAMs) that are
      responsible for homophilic and heterophilic cell-cell interactions. One relevant
      CAM may be the calcium-dependent transmembrane glycoprotein E-cadherin. To
      investigate the involvement of E-cadherin in breast cancer metastasis to bone, we
      used an in vivo model in which osteolytic bone metastases preferentially occur
      after injections of cancer cells directly into the arterial circulation through
      the left ventricle of the hearts of nude mice. We have found that E-cadherin
      negative human breast cancer cells MDA-MB-231 (MDA-231) develop radiographically
      detectable multiple osteolytic bone metastases and cachexia in this model.
      However, MDA-231 breast cancer cells that were transfected with E-cadherin cDNA
      showed a dramatically impaired capacity to form osteolytic metastases and induce
      cachexia. Histological and histomorphometrical analyses of bones of mice bearing
      mock-transfected MDA-231 revealed aggressive metastatic tumor, whereas metastatic
      tumor burden was significantly decreased in the bones of mice bearing E-cadherin
      expressing MDA-231. Nude mice bearing E-cadherin-transfected MDA-231 breast
      cancer cells survived longer than mice bearing mock-transfected MDA-231 breast
      cancer cells. Anchorage-dependent and -independent growth in culture and tumor
      enlargement in the mammary fat pad of nude mice were unchanged between mock
      transfected and E-cadherin-expressing MDA-231, suggesting that these differences
      in metastatic behavior are not due to an impairment of cell growth and tumor
      igenicity. Our results show the suppressive effects of E-cadherin expression on
      bone metastasis by circulating breast cancer cells and suggest that the
      modulation of expression of this CAM may reduce the destructive effects of breast
      cancer cells on bone.

PMID- 8752181
TI  - Prediction of the infarct-related artery in acute myocardial infarction by a
      scoring system using summary ST-segment and T-wave changes.
AB  - We developed a scoring system to predict the artery responsible for an acute
      myocardial infarction (AMI) using ST-segment and T-wave changes on the initial
      electrocardiogram (ECG) using data from 228 patients (development set) with
      symptoms compatible with AMI and tested in a similar group of 223 patients (test
      set) from the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI-5)
      Trial. Using stepwise logistic regression we were able to accurately predict the
      left anterior descending (LAD), right, or left circumflex (LC) coronary artery as
      the infarct-related artery using 2 variables: (1) the summation of the ST-segment
      elevation in leads V1 to V4; and (2) the summation of the T-wave negativity in
      leads I, aVL, and V5. In the development set, these 2 variables demonstrated
      respective sensitivity and specificity of 98% and 90% for LAD lesions, 82% and
      85% for right narrowings, and 82% and 84% for LC narrowings. In the test set, the
      sensitivity and specificity were 97% and 95% for LAD lesions, 85% and 86% for
      right lesions, and 73% and 60% for LC coronary artery lesions. Information easily
      obtained on the ECG can accurately predict the likelihood of the LAD, right, or
      LC artery as the infarct-related artery. This may be useful in the decision to
      administer thrombolytic treatment.

PMID- 8752182
TI  - Distortion of the terminal portion of the QRS on the admission electrocardiogram
      in acute myocardial infarction and correlation with infarct size and long-term
      prognosis (Thrombolysis in Myocardial Infarction 4 Trial).
AB  - Previous studies have shown an association between distortion of the terminal
      portion of the QRS (QRS[+] pattern: emergence of the J point > or = 50%. of the R
      wave in leads with qR configuration or disappearance of the S wave in leads with
      an Rs configuration) on admission and in-hospital mortality in acute myocardial
      infarction (AMI). However, the mechanism for this association is not known. We
      assessed the relation between QRS(+) pattern and coronary angiographic findings,
      infarct size, and long-term prognosis in the Thrombolysis In Myocardial
      Infarction 4 trial. Patients were allocated into 2 groups based on the presence
      (QRS[+], n = 85) or absence (QRS[-], n = 293) of QRS distortion. The QRS(+)
      patients were older (mean +/- SD: 61.1 +/- 10.6 vs 57.5 +/- 10.6 years, p =
      0.004), had more anterior AMI (49% vs 37%, p = 0.04), and less previous angina
      (42% vs 54%, p = 0.05). QRS(+) patients had larger infarct size as assessed by
      creatine kinase release over 24 hours (209 +/- 147 vs 155 +/- 129, p = 0.003),
      and predischarge sestamibi (MIBI) defect (17.9 +/- 15.9% vs 11.2 +/- 13.4%, p
      <0.001). When adjusting for difference in baseline characteristics, p values for
      the differences in 24-hour creatine kinase release were 0.03 and 0.64 for
      anterior and nonanterior AMI, respectively, and for MIBI defect size 0.03 and
      0.02, respectively. One-year mortality (18% vs 6%, p = 0.03) was higher and the
      weighted end point of death, reinfarction, heart failure, or left ventricular
      ejection fraction <40% (0.33 +/- 0.37 vs 0.24 +/- 0.32, p = 0. 13), tended to be
      higher in the anterior AMI patients with QRS(+). No difference in clinical
      outcome was found in patients with non-anterior AMI. These findings suggest that
      this simple electrocardiographic definition of presence of QRS(+) pattern on
      admission may provide an early estimation of infarct size and long-term
      prognosis, especially in anterior AMI.

PMID- 8752183
TI  - Value of dobutamine stress echocardiography in determining the prognosis of
      patients with known or suspected coronary artery disease.
AB  - Although the accuracy of dobutamine stress echo (DSE) for detecting coronary
      artery disease (CAD) has been established, its role in determining prognosis is
      less well defined. The purpose of this study was to evaluate the prognostic
      significance of DSE in patients with known or suspected CAD. Follow-up was
      obtained on 291 patients an average of 15 months after clinically indicated DSE.
      Studies were stratified with respect to resting and inducible wall motion
      abnormalities into 1 of 4 responses: normal, ischemic, fixed, and mixed. Hard end
      points of nonfatal myocardial infarction and cardiac death were tabulated for
      outcome. Statistically significant differences in the incidence of hard cardiac
      end points were noted for 2 of 4 DSE responses. A normal DSE was associated with
      a statistically lower likelihood of a hard cardiac event than was a DSE
      demonstrating resting or inducible abnormalities (p = 0.001). DSE with a mixed
      response (resting abnormality with additional inducible ischemia) was associated
      with a higher likelihood of cardiac events by multivariate analysis (p = 0.003).
      By multiple logistic regression analysis of dobutamine response, age, and cardiac
      risk factors, only a mixed response on DSE was independently associated with the
      occurrence of a hard cardiac event in the follow-up period. In addition, left
      ventricular dysfunction on the resting echocardiogram was associated with a worse
      prognosis in patients with major noncardiac disease. We conclude that dobutamine
      response is an independent predictor of cardiac events compared with traditional
      risk factor analysis and that DSE can identify high- and low-risk subsets of
      patients with known or suspected CAD.

PMID- 8752184
TI  - Cost-effectiveness of pravastatin in secondary prevention of coronary artery
      disease.
AB  - This study analyzed the cost-effectiveness of pravastatin in secondary prevention
      of coronary artery disease (CAD). The projected risk model in 445 male patients
      with established CAD and moderately elevated serum low-density lipoprotein
      cholesterol used results data from 2 placebo-controlled plaque regression trials:
      Pravastatin Limitation of Atherosclerosis in the Coronary Arteries and
      Pravastatin, Lipids, and Atherosclerosis in the Carotids. Framingham Heart Study
      data were used to project the risk of mortality 10 years after myocardial
      infarction (MI) for incremental male patients in the placebo group who had MI. A
      Markov process was used to estimate life-years saved, and decision analysis was
      used to estimate cost. Depending on the patient-risk profile, the midrange
      estimated cost per life-year saved with pravastatin in secondary prevention of
      CAD varied from $7,124 to $12,665, which is favorable compared with other widely
      accepted medical interventions.

PMID- 8752185
TI  - Comparison of dobutamine transesophageal echocardiography and dobutamine magnetic
      resonance imaging for detection of residual myocardial viability.
AB  - A dobutamine-induced contraction reserve in akinetic but viable myocardium,
      observed by echocardiography or magnetic resonance imaging (MRI), is a reliable
      indicator of myocardial viability. However, the comparative diagnostic accuracy
      of these 2 techniques is unknown. Therefore, 43 patients with myocardial
      infarction (infarct age > or = 4 months) and regional akinesia underwent
      dobutamine transesophageal echocardiography (TEE) and dobutamine MRI (10 microg
      dobutamine/ min/kg). Both imaging techniques were compared with the reference
      standard 18F-fluorodeoxyglucose positron emission tomography (FDG PET). An
      infarct region was considered viable if a dobutamine contraction reserve could be
      assessed visually by TEE or quantitatively by MRI in > or = 50% of segments
      graded "a" or dyskinetic at rest. Infarct regions were graded viable by PET if
      FDG uptake was > or = 50% of the maximal FDG uptake in a region with normal wall
      motion by left ventriculography. A dobutamine contraction reserve was found in 21
      of 43 patients (49%) by TEE and MRI. A viable infarct region by FDG PET was
      diagnosed in 26 of 43 patients (60%). FDG uptake and dobutamine TEE were
      concordant in 36 of 43 patients (84%) and dobutamine MRI and FDG PET were
      concordant in 38 of 43 patients (88%). Sensitivity and specificity of dobutamine
      TEE and dobutamine MRI for FDG PET-defined myocardial viability were 77% versus
      81% and 94% versus 100%, respectively. Both imaging techniques yielded similar
      results for the detection of myocardial viability as defined by FDG uptake, with
      a slightly higher sensitivity and specificity for the quantitatively evaluated
      dobutamine contraction reserve by MRI.

PMID- 8752186
TI  - Efficacy and tolerability of lovastatin in 459 African-Americans with
      hypercholesterolemia.
AB  - A paucity of substantive data from clinical drug trials is available specifically
      evaluating the effects of therapy for hypercholesterolemia in African-Americans,
      even though a substantial number are candidates for medical advice and
      intervention for high blood cholesterol. The efficacy and safety of lovastatin in
      459 African-Americans with hypercholesterolemia were studied in the Expanded
      Clinical Evaluation of Lovastatin study, a multicenter, double-blind, diet- and
      placebo-controlled trial. This trial involved 8,245 patients who were randomly
      assigned, regardless of race, to receive placebo or lovastatin at doses of 20 mg
      once daily, 40 mg once daily, 20 mg twice daily, or 40 mg twice daily for 48
      weeks. Among African-Americans, lovastatin produced sustained, dose-related (p
      <0.001) decreases in low-density lipoprotein cholesterol (20% to 38%), total
      cholesterol (14% to 28%), and triglycerides (8% to 15%). From 75% to 96% of
      African-Americans treated with lovastatin achieved the National Cholesterol
      Education Program goal of low-density lipoprotien cholesterol <160 mg/di, and
      from 33% to 71% achieved the goal <130 mg/di. The safety profile of lovastotin in
      African-Americans was generally favorable. A relatively high incidence of
      creatine kinase levels greater than the upper limit of normal was observed in
      African-Americans during the study, i.e., 63% in the placebo group and similar
      levels in lovastatin treatment groups. Lovastatin is highly effective and
      generally well tolerated as therapy for primary hypercholesterolemia in African
      Americans.

PMID- 8752187
TI  - Atrial fibrillation with left atrial spontaneous contrast detected by
      transesophageal echocardiography is a potent risk factor for stroke.
AB  - Nonrheumatic atrial fibrillation (AF) frequently coexists with other risk factors
      for cerebral ischemia. This study was originally designed to determine which
      combinations of clinical and echocardiographic abnormalities were most closely
      associated with the risk of cerebral ischemic events. Patients with cerebral
      ischemic events (n = 214) and community-based control subjects (n = 201)
      underwent transesophageal echocardiography and carotid artery imaging. Adjusted
      odds ratios (ORs) were determined using multiple logistic regression analysis.
      Independent risk factors for cerebral ischemia included diabetes, carotid
      stenosis, aortic sclerosis, left ventricular dysfunction, left ventricular
      hypertrophy, left atrial (LA) spontaneous contrast, and proximal aortic atheroma.
      Nonrheumatic AF in combination with LA spontaneous contrast and LA enlargement
      showed a strong association with cerebral ischemic events (OR 33.7 [95%
      confidence interval 4.53 to 251]). In subjects with sinus rhythm or nonrheumatic
      AF, LA enlargement was not associated with an increased risk of cerebral ischemic
      events in the absence of LA spontaneous contrast. However, only 2 patients and 1
      control subject had nonrheumatic AF without LA spontaneous contrast or LA
      enlargement. Therefore, study of a larger number of subjects is required to
      address the issue of whether nonrheumatic AF itself carries increased risk. The
      combination of nonrheumatic AF with LA spontaneous contrast is a potent risk
      factor for cerebral ischemia. Ascertaining the risk factor in nonrheumatic AF
      requires adequate examination for underlying cardiac, aortic, and carotid
      vascular disease. Transesophageal echocardiography may contribute to this
      assessment.

PMID- 8752188
TI  - Safety and tolerability of long-term propafenone therapy for supraventricular
      tachyarrhythmias. The Propafenone Multicenter Study Group.
AB  - An important issue regarding the long-term use of antiarrhythmic drugs concerns
      the safety of these agents, particularly with regard to cardiac toxicity.
      Propafenone is an effective drug for preventing supraventricular tachyarrhythmia,
      but the incidence of side effects during longterm therapy in patients with such
      arrhythmias has not been adequately reported. A total of 480 patients received
      oral propafenone as therapy for symptomatic atrial fibrillation, atrial flutter,
      or supraventricular tachycardia. During the follow-up (mean 14.4 months), 290
      patients (60%) discontinued propafenone therapy, but in only 70 patients (15%)
      was the reason for discontinuation an adverse drug reaction. Overall, 284
      patients (59%) experienced at least 1 adverse reaction, and the incidence was
      related to dose and age >65 years. The overall incidence of side effects was not
      related to structural heart disease; however, cardiovascular toxicity including
      arrhythmia aggravation, congestive heart failure, and serious conduction
      disturbances occurred more often in those with heart disease (20% vs 13%).
      Sixteen patients died during drug therapy, but in only 1 case was the drug
      considered contributory. For patients with a supraventricular arrhythmia,
      propafenone was well tolerated and was infrequently discontinued because of side
      effects. The incidence of serious cardiac toxicity when propafenone was used to
      treat supraventricular arrhythmia was low, and these side effects were more
      frequent in patients with structural heart disease.

PMID- 8752189
TI  - Transesophageal echocardiographic evaluation of left atrial appendage function
      and spontaneous contrast formation after chemical or electrical cardioversion of
      atrial fibrillation.
AB  - Changes in left atrial (LA) appendage pulsed-wave Doppler velocities and changes
      in grades of spontaneous contrast occur immediately after electrical
      cardioversion of atrial fibrillation (AF) using transesophageal echocardiography
      (TEE). The effect of sequential ineffective electrical cardioversion attempts or
      chemical cardioversion on these parameters is unknown. TEE was performed in 23
      patients with chronic AF. Doppler velocities and grades of spontaneous contrast
      were assessed before and after each cardioversion attempt until sinus rhythm was
      achieved. Doppler emptying and filling velocities were significantly decreased
      after electrical (0.39 +/- 0.14 vs 0.27 +/- 0.16 [p = 0.01] and 0.43 +/- 0. 18 vs
      0.30 +/- 0.14 m/s [p = 0.01]) or chemical cardioversion to sinus rhythm (0.65 +/-
      0.18 vs 0.31 +/- 0.06 [p = 0.03] and 0.64 +/- 0.22 vs 0.44 +/- 0.17 m/s [p =
      0.04]). Spontaneous contrast developed in 1 of 3 patients after chemical
      conversion to sinus rhythm and was present in 11 of 20 patients before electrical
      cardioversion, developing in 4 patients and intensifying in 2 patients
      immediately after successful cardioversion. These phenomena were not seen after
      ineffective electrical or chemical cardioversion attempts. This suggests that
      restoration of sinus rhythm is in itself responsible for these phenomena, not the
      method by which sinus rhythm is achieved.

PMID- 8752190
TI  - Impact of medical therapy on pulmonary hypertension in patients with congestive
      heart failure awaiting cardiac transplantation.
AB  - Pulmonary artery (PA) hypertension in transplant recipients increases mortality
      from right heart failure following heart transplantation. We examined the impact
      of long-term medical therapy on the severity of PA hypertension in patients with
      end-stage congestive heart failure on a transplant waiting list. The initial and
      final, quarterly right heart catheterization data on 60 patients (50 men, aged 50
      +/- 9 years, New York Heart Association class III to IV) awaiting heart
      transplantation were analyzed and the patients divided into 2 groups: group A,
      those with persistent elevated systolic PA pressures throughout the 10-month
      follow-up (n = 31 of 60), and group B, those who had any decrease in systolic PA
      pressure during that period (n = 29 of 60). Group A had no change in
      hemodynamics. Group B had a significant decrease( +/- SD) in right atrial (11 +/-
      7 to 5 +/- 4 mm Hg), PA (57 +/- 11 to 37 +/- 11 mm Hg), and PA wedge (25 +/- 9 to
      14 +/- 7 mm Hg) pressures, with increases in cardiac output (3.8 +/- 0.9 to 4.7
      +/- 1.1 L/min) and ejection fraction (18 +/- 6% to 27 +/- 11%) (p < 0.05). The
      combined end point of transplant or death occurred in 28 of 31 patients (90%) in
      group A versus 14 of 29 (50%) in group B (p = 0.0004). Ischemic etiology was
      present in 71 % of patients in group A versus 68% with idiopathic dilated
      cardiomyopathy in group B (p = 0.003). The reversibility of PA hypertension
      rather than its initial severity is predictive of patient clinical outcome.
      Idiopathic, as opposed to ischemic, cardiomyopathy responds better to medical
      therapy.

PMID- 8752191
TI  - Value of systolic pulmonary venous flow reversal and color Doppler jet
      measurements assessed with transesophageal echocardiography in recognizing severe
      pure mitral regurgitation.
AB  - We evaluated the value of color and pulsed Doppler transesophageal
      echocardiographic parameters and of V waves in estimating the severity of mitral
      regurgitation (MR) in 62 consecutive patients (38 men and 24 women, aged 39 to 80
      years) with angiographically proven chronic pure MR (15 grade I/II, 47 grade
      III/IV). Twenty patients were examined before cardiac surgery under general
      anesthesia. Sensitivity, specificity, and positive and negative predictive values
      of systolic pulmonary venous flow reversal for the presence of grade III/IV MR
      were 87%, 93%, 98%, and 64%, respectively, these were for jet areas > or = 8.0
      cm2--66%, 100%, 100%, and 48%, for jet lengths > or = 50 mm--70%, 87%, 94%, and
      48%, for enlarged V waves--86%, 38%, 83%, and 43%, and for either flow reversal
      or a jet area > or = 8.0 cm2--96%, 93%, 98%, and 88%. We conclude that a
      combination of measurements improved the negative predictive value considerably,
      which is of importance in a population with a high pretest probability of severe
      MR. Enlarged V waves are not reliable in predicting severe MR. The optimal cutoff
      value for jet area and jet length was lower in anesthesized patients than in
      conscious patients; in anesthesized patients, sensitivity, specificity, and
      positive and negative predictive values of jet area > or = 5.0 CM2 for grade
      III/IV MR were 67%, 100%, 100%, and 50%, respectively; these were 87%, 100%,
      100%, and 71% for flow reversal. Because the results of mitral repair are often
      evaluated with transesophageal echocardiography during surgery, our findings have
      clinical implications for evaluation of severe MR in anesthesized patients:
      pulmonary venous flow direction is the first-choice measure; jet area can be used
      when a low cutoff point is chosen.

PMID- 8752192
TI  - Effects of diltiazem on left ventricular systolic and diastolic function in
      hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HC) is characterized by impaired diastolic function,
      and left ventricular (LV) outflow tract obstruction in about one-fourth of
      patients. Verapamil improves diastolic properties, but may have dangerous adverse
      effects. This study investigates the effects of diltiazem on hemodynamics and LV
      function in 16 patients with HC who were studied with cardiac catheterization and
      simultaneous radionuclide angiography. Studies were performed during atrial
      pacing (15 beats above spontaneous rhythm) at baseline and during intravenous
      diltiazem administration (0.25 mg x kg(-1) over 2 minutes, and 0.014 mg x kg(-1)
      x min(-1). Diltiazem induced a systemic vasodilation (cardiac index: 3.4 +/- 1.0
      to 4.0 +/- 1.0 L x min(-1) x m(-2), p = 0.003; aortic systolic pressure: 116 +/-
      16 to 107 +/- 19 mm Hg, p = 0.007; systemic resistance index: 676 +/- 235 to 532
      +/- 193 dynes x s x cm(-5) x m(-2), p = 0.006), not associated with changes in
      the LV outflow tract gradient. The end-systolic pressure/volume ratio decreased
      (30 +/- 42 to 21 +/- 29 mm Hg x ml(-1) x m(-2); p = 0.044). Pulmonary artery
      wedge pressure (11 +/- 5 to 15 +/- 6 mm Hg, p = 0.006), and peak filling rate
      increased (4.1 +/- 1.3 to 6.0 +/- 2.4 stroke counts x s(-1), p = 0.004). The time
      constant of isovolumetric relaxation tau decreased (74 +/- 40 to 59 +/- 38 ms, p
      = 0.045). The constant of LV chamber stiffness did not change. Thus, active
      diastolic function is improved by the acute administration of diltiazem by both
      direct action and changes in hemodynamics and loading conditions. LV outflow
      tract gradient does not increase despite systemic vasodilation. In some patients,
      however, a marked increase in obstruction and a potentially harmful elevation in
      pulmonary artery wedge pressure do occur. Passive diastolic function is not
      affected.

PMID- 8752193
TI  - QT dispersion and arrhythmic events in idiopathic dilated cardiomyopathy.
AB  - QT dispersion was measured in the 12-lead standard electrocardiogram in 107
      patients with idiopathic dilated cardiomyopathy (IDC) and 100 age- and sex-
      matched controls without structural heart disease. All 107 study patients with
      IDC were prospectively followed in order to determine possible associations
      between QT dispersion and arrhythmic events, i.e., sustained ventricular
      tachycardia, ventricular fibrillation, or sudden death. QT dispersion, rate
      corrected QT dispersion, and adjusted QTc dispersion, which takes account of the
      number of leads measured, were significantly greater in patients with IDC than in
      controls. During 13 +/- 7 months follow-up, arrhythmic events occurred in 12 of
      107 study patients with IDC (11%). QT dispersion was increased in patients with
      versus without arrhythmic events during follow-up (76 +/- 17 vs 60 +/- 26 ms;
      p=0.03). QTc dispersion and adjusted QTc dispersion were not significantly
      different between patients with and without arrhythmic events (80 +/- 21 vs 75 +/
      35 ms, and 27 +/- 6 vs 24 +/- 10 ms, respectively). Thus, although QT dispersion
      was increased in patients with IDC and arrhythmic events during follow-up, its
      usefulness for arrhythmia risk prediction was limited by the large overlap of QT
      dispersion between patients with and without arrhythmic events.

PMID- 8752194
TI  - Assessment of left ventricular outflow in hypertrophic cardiomyopathy using
      anyplane and paraplane analysis of three-dimensional echocardiography.
AB  - This study analyzes the alterations in size and geometry of the left ventricular
      (LV) outflow tract that occur in hypertrophic cardiomyopathy (HC) using
      transthoracic 3-dimensional echocardiography. Transthoracic 3-dimensional
      echocardiography was performed in 17 patients with HC (4 after myectomy) and in
      10 normal subjects. Images were acquired with the rotational approach, with
      electrocardiographic and respiratory gating. From the 3-dimensional datasets,
      short-axis parallel slicing of the LV outflow tract at a 1mm distance was
      performed at the onset of systole. For each slice, cross-sectional area and
      maximal and minimal diameter were calculated. Reconstruction of the LV outflow
      tract could be displayed in 3 dimensions in all patients, allowing orientation
      and clear definition of the irregular geometry. In patients with HC, the minimal
      LV outflow tract cross-sectional area was smaller than in normal subjects (2.3 +/
      1.0 vs 5.0 +/- 0.9 cm(2), p < 0.0001). The ratio between maximal and minimal
      cross-sectional areas was higher in patients with HC than in normal subjects (2.6
      +/- 0.9 vs 1.4 +/- 0.2, p <0.0001). The ratio between maximal and minimal
      diameter of the smallest cross section of the LV outflow tract was also
      significantly higher in patients with HC than in normal subjects (1.6 +/- 0.3 vs,
      1.2 +/- 0. 1, p <0.001); a value of 1.36 separated normal subjects from HC
      patients without previous myectomy. In conclusion, precordial 3-dimensional
      echocardiography allows detailed qualitative and quantitative information on the
      LV outflow tract. Patients with HC are characterized by a highly eccentric and
      asymmetric shape of the LV outflow tract, and by a smaller minimal cross
      sectional area than that seen in normal subjects.

PMID- 8752195
TI  - Regional right ventricular dysfunction detected by echocardiography in acute
      pulmonary embolism.
AB  - This study analyzed the regional pattern of right ventricular (RV) dysfunction on
      transthoracic echocardiograms in patients with and without acute pulmonary
      embolism. Quantitative (centerline) and qualitative (wall motion score) analyses
      of segmental RV free wall motion were performed on a "training" cohort of 41
      patients (group 1), including 14 patients with acute pulmonary embolism, 9
      patients with primary pulmonary hypertension, and 18 normal subjects. Patients
      with acute pulmonary embolism had a distinct regional pattern of RV dysfunction,
      with akinesia of the mid-free wall (centerline excursion: -0.2 +/- 0.8 mm, p =
      0.0001 vs normal) but normal motion at the apex (centerline excursion: 5.7 +/-
      0.8 mm, p = NS vs normal). In contrast, patients with primary pulmonary
      hypertension had abnormal wall motion in all regions (p <0.03 vs normal). This
      echocardiographic finding of normal wall motion at the apex and abnormal wall
      motion in the mid-free wall in acute pulmonary embolism was then tested in a
      "validation" cohort of 85 patients (group 2), consisting of hospitalized patients
      with RV dysfunction from any cause, including 13 patients with acute pulmonary
      embolism. The finding had a 77% sensitivity and a 94% specificity for the
      diagnosis of acute pulmonary embolism, with a positive predictive value of 71%
      and a negative predictive value of 96%. Thus, a distinct echocardiographic
      pattern of regional RV dysfunction, in which the apex is spared occurs in acute
      pulmonary embolism. This finding should raise the level of clinical suspicion for
      the diagnosis of acute pulmonary embolism.

PMID- 8752196
TI  - Coronary artery calcium detected by digital fluoroscopy and risk factors in
      healthy subjects.
AB  - Coronary artery calcium detected by digital fluoroscopy is closely associated
      with known risk factors of coronary artery disease in asymptomatic low-risk
      populations. Even in the absence of significant luminal narrowing, this may not
      be an innocent finding, and subjects with coronary calcium may be at greater risk
      for developing obstruction and clinical disease.

PMID- 8752197
TI  - Safety, tolerability, and efficacy of a glucose-insulin-potassium-magnesium
      carnitine solution in acute myocardial infarction.
AB  - Fifty-four patients with AMI were treated with a front-loaded 15-hour infusion of
      hypertonic glucose, insulin, potassium, magnesium, and L-carnitine in addition to
      usual therapy. This metabolic solution was well tolerated, free of serious side
      effects, and reduced the incidence of morbid events.

PMID- 8752198
TI  - Usefulness of transdermal scopolamine for vasovagal syncope.
AB  - We studied short-term effectiveness of transdermal scopolamine in a group of
      patients with unexplained syncope provoked during head-up tilt testing. This
      double-blind randomized trial of transdermal scopolamine demonstrated no
      significant effect of preventing vasovagal syncope.

PMID- 8752199
TI  - Excessive papillary muscle traction and dilated mitral annulus in mitral valve
      prolapse without mitral regurgitation.
AB  - This study demonstrated excessive papillary muscle displacement during peak
      systole but normal mitral annulus function during the cardiac cycle in patients
      with mitral valve prolapse and no mitral regurgitation. The excessive papillary
      muscle displacement may play an important role in the pathogenesis of the
      superior displacement of mitral leaflets in patients with mitral valve prolapse.

PMID- 8752200
TI  - Racial and gender differences in endothelin-1.
AB  - In summary, ET-1 levels were significantly increased in black men compared with
      white men. This racial difference could have important research implications if
      increased ET-1 levels are linked to left ventricular hypertrophy and other
      cardiovascular diseases, and it may serve as a foundation for future studies.

PMID- 8752201
TI  - Magnetic deflection forces from atrial septal defect and patent ductus arteriosus
      occluding devices, stents, and coils used in pediatric-aged patients.
AB  - Magnetic deflection forces and imaging artifact were assessed for 13 pediatric
      interventional cardiology devices. The magnetic deflection forces incurred by
      these devices are small compared with physiologic forces experienced in the
      cardiovascular system.

PMID- 8752202
TI  - Acute myocardial infarction complicating viper bite.
AB  - An acute myocardial infarction was induced by Vipera palaestinea venom in a young
      patient. The diagnosis was confirmed by cardiac catheterization, which showed a
      segmental contraction abnormality but normal coronary arteries.

PMID- 8752203
TI  - Sudden death while playing tennis due to a tear in ascending aorta (without
      dissection) and probable transient compression of the left main coronary artery.

PMID- 8752204
TI  - Prospective study of extraction atherectomy in patients with acute myocardial
      infarction.
AB  - Although percutaneous transluminal coronary angioplasty (PTCA) has been an
      effective treatment for primary reperfusion in acute myocardial infarction,
      patients with thrombolytic ineligibility, thrombolytic failure, cardiogenic
      shock, and vein graft occlusion remain at high risk for complications with PTCA
      treatment. The transluminal extraction catheter may be useful for treatment for
      such patients owing to its ability to aspirate thrombus. At 2 clinical centers,
      extraction atherectomy was prospectively evaluated in 100 patients (age 62 +/- 10
      years). High-risk features included thrombolytic failure in 40%, postinfarct
      angina in 28%, presence of angiographic thrombus in 66%, presence of cardiogenic
      shock in 11%, and a saphenous vein graft occlusion in 29%. Procedural success,
      defined as a final residual stenosis <50% and Thrombolysis in Myocardial
      Infarction 2 or 3 grade flow, was seen in 94%. Events during the hospitalization
      included death in 5%, bypass surgery in 4%, and blood transfusion in 18%. In a
      substudy, patients enrolled at William Beaumont Hospital (n = 65) underwent
      elective predischarge angiography, which revealed a patent infarct-related vessel
      in 95%. These patients were also followed for 6 months with angiographic follow
      up in 60%. Target vessel revascularization was necessary in 38%, and 6-month
      mortality was 10%. Although long-term vessel patency was 90%, angiographic
      restenosis occurred in 68%. Acute myocardial infarction patients can be treated
      with extraction atherectomy with a high technical success rate and a low
      incidence of complication. Infarct artery patency at 1 week and 6 months was
      excellent; however, angiographic restenosis remains a problem. Extraction of
      thrombus in this high-risk group of patients is associated with low in-hospital
      mortality and a high rate of vessel patency at 6 months.

PMID- 8752205
TI  - Serpentine proteins slither into the wingless and hedgehog fields.

PMID- 8752206
TI  - A signaling pathway to translational control.

PMID- 8752207
TI  - The role of the genome project in determining gene function: insights from model
      organisms.

PMID- 8752208
TI  - TGFbeta1 inhibits the formation of benign skin tumors, but enhances progression
      to invasive spindle carcinomas in transgenic mice.
AB  - TGFbeta1 has been implicated in cell cycle control and carcinogenesis. To address
      the exact function of TGFbeta1 in skin carcinogenesis in vivo, mice with TGFbeta1
      expression targeted to keratinocytes were subjected to long-term chemical
      carcinogenesis treatment. TGFbeta1 showed biphasic action during multistage skin
      carcinogenesis, acting early as a tumor suppressor but later enhancing the
      malignant phenotype. The transgenics were more resistant to induction of benign
      skin tumors than controls, but the malignant conversion rate was vastly
      increased. There was also a higher incidence of spindle cell carcinomas, which
      expressed high levels of endogenous TGFbeta3, suggesting that TGFbeta1 elicits an
      epithelial-mesenchymal transition in vivo and that TGFbeta3 might be involved in
      maintenance of the spindle cell phenotype. The action of TGFbeta1 in enhancing
      malignant progression may mimic its proposed function in modulating epithelial
      cell plasticity during embryonic development.

PMID- 8752209
TI  - MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is
      functionally mutated in colorectal carcinoma.
AB  - The MAD-related (MADR) family of proteins are essential components in the
      signaling pathways of serine/threonine kinase receptors for the transforming
      growth factor beta (TGFbeta) superfamily. We demonstrate that MADR2 is
      specifically regulated by TGFbeta and not bone morphogenetic proteins. The gene
      for MADR2 was found to reside on chromosome 18q21, near DPC4, another MADR
      protein implicated in pancreatic cancer. Mutational analysis of MADR2 in sporadic
      tumors identified four missense mutations in colorectal carcinomas, two of which
      display a loss of heterozygosity. Biochemical and functional analysis of three of
      these demonstrates that the mutations are inactivating. These findings suggest
      that MADR2 is a tumor suppressor and that mutations acquired in colorectal
      carcinomas may function to disrupt TGFbeta signaling.

PMID- 8752210
TI  - The Cdk-activating kinase (CAK) from budding yeast.
AB  - Activation of the cyclin-dependent kinases to promote cell cycle progression
      requires their association with cyclins as well as phosphorylation of a threonine
      (residue 161 in human p34cdc2). This phosphorylation is carried out by CAK, the
      Cdk-activating kinase. We have purified and cloned CAK from S. cerevisiae. Unlike
      CAKs from other organisms, Cak1p is active as a monomer, has full activity when
      expressed in E. coli, and is not a component of the basal transcription factor,
      TFIIH. A temperature-sensitive mutation in CAK1 confers a G2 delay accompanied by
      low Cdc28p protein kinase activity and shows genetic interactions with altered
      expression of the gene for the major mitotic cyclin, CLB2. Our data raise the
      intriguing possibility that p40MO15-cyclin H-MAT1, identified as the predominant
      CAK in vertebrate cell extracts, may not function as a physiological CAK.

PMID- 8752211
TI  - Civ1 (CAK in vivo), a novel Cdk-activating kinase.
AB  - Cyclin-dependent protein kinases (Cdks) play key roles in regulating cell
      division and gene expression. Most Cdks require binding of a cyclin and
      phosphorylation by a Cdk-activating kinase (CAK) to be active. We report the
      identification of Civ1 (CAK in vivo), a novel CAK activity in S. cerevisiae. Civ1
      is most similar in sequence to the Cdks, but unlike them is active as a monomer
      and may thus be the founding member of a novel family of kinases. Civ1 binds
      tightly to and phosphorylates Cdc28, thereby allowing its subsequent activation
      by the binding of a cyclin. The CIV1 gene is essential for yeast cell viability,
      and Cdc28 phosphorylation and activity are conditionally inhibited in a civ1-4
      temperature-sensitive mutant. Civ1 is the only CAK for which there are genetic
      data indicating that its activity is physiologically relevant in vivo.

PMID- 8752212
TI  - Structure of the FGF receptor tyrosine kinase domain reveals a novel
      autoinhibitory mechanism.
AB  - The crystal structure of the tyrosine kinase domain of fibroblast growth factor
      receptor 1 (FGFR1K) has been determined in its unliganded form to 2.0 angstroms
      resolution and in complex with with an ATP analog to 2.3 angstrosms A resolution.
      Several features distinguish the structure of FGFR1K from that of the tyrosine
      kinase domain of the insulin receptor. Residues in the activation loop of FGFR1K
      appear to interfere with substrate peptide binding but not with ATP binding,
      revealing a second and perhaps more general autoinhibitory mechanism for receptor
      tyrosine kinases. In addition, a dimeric form of FGFR1K observed in the crystal
      structure may provide insights into the molecular mechanisms by which FGF
      receptors are activated. Finally, the structure provides a basis for
      rationalizing the effects of kinase mutations in FGF receptors that lead to
      developmental disorders in nematodes and humans.

PMID- 8752214
TI  - The Spemann organizer signal noggin binds and inactivates bone morphogenetic
      protein 4.
AB  - Signals released by the Spemann organizer of the amphibian gastrula can directly
      induce neural tissue from ectoderm and can dorsalize ventral mesoderm to form
      muscle. The secreted polypeptide noggin mimics these activities and is expressed
      at the appropriate time and place to participate in the organizer signal. Neural
      induction and mesoderm dorsalization are antagonized by bone morphogenetic
      proteins (BMPs), which induce epidermis and ventral mesoderm instead. Here we
      report that noggin protein binds BMP4 with high affinity and can abolish BMP4
      activity by blocking binding to cognate cell-surface receptors. These data
      suggest that noggin secreted by the organizer patterns the embryo by interrupting
      BMP signaling.

PMID- 8752213
TI  - Dorsoventral patterning in Xenopus: inhibition of ventral signals by direct
      binding of chordin to BMP-4.
AB  - Chordin (Chd) is an abundant protein secreted by Spemann organizer tissue during
      gastrulation. Chd antagonizes signaling by mature bone morphogenetic proteins
      (BMPs) by blocking binding to their receptors. Recombinant Xenopus Chd binds to
      BMP-4 with high affinity (KD, 3 x 10(-10) M), binding specifically to BMPs but
      not to activin or TGF-beta1. Chd protein is able to dorsalize mesoderm and to
      neuralize ectoderm in Xenopus gastrula explants at 1 nM. We propose that the
      noncell-autonomous effects of Spemann's organizer on dorsoventral patterning are
      executed in part by diffusible signals that directly bind to and neutralize
      ventral BMPs during gastrulation.

PMID- 8752215
TI  - The Xenopus dorsalizing factor noggin ventralizes Drosophila embryos by
      preventing DPP from activating its receptor.
AB  - noggin is expressed in the Spemann organizer region of the Xenopus embryo and can
      promote dorsal cell fates within the mesoderm and neural development within the
      overlying ectoderm. Here, we show that noggin promotes ventral development in
      Drosophila, specifying ventral ectoderm and CNS in the absence of all endogenous
      ventral-specific zygotic gene expression. We utilize constitutively active forms
      of the dpp receptors to demonstrate that noggin blocks dpp signaling upstream of
      dpp receptor activation. These results suggest a mechanistic basis for the action
      of Spemann's organizer during Xenopus development and provide further support for
      the conservation of dorsal-ventral patterning mechanisms between arthropods and
      chordates.

PMID- 8752216
TI  - G proteins are required for spatial orientation of early cell cleavages in C.
      elegans embryos.
AB  - Heterotrimeric G proteins are signal-transducing molecules activated by seven
      transmembrane domain receptors. In C. elegans, gpb-1 encodes the sole Gbeta
      subunit; therefore, its inactivation should affect all heterotrimeric G protein
      signaling. When maternal but no zygotic gpb-1 protein (GPB-1) is present,
      development proceeds until the first larval stage, but these larvae show little
      muscle activity and die soon after hatching. When, however, the maternal
      contribution of GPB-1 is also reduced, spindle orientations in early cell
      divisions are randomized. Cell positions in these embryos are consequently
      abnormal, and the embryos die with the normal number of cells and well
      differentiated but abnormally distributed tissues. These results indicate that
      maternal G proteins are important for orientation of early cell division axes,
      possibly by coupling a membrane signal to centrosome position.

PMID- 8752217
TI  - Cortexillins, major determinants of cell shape and size, are actin-bundling
      proteins with a parallel coiled-coil tail.
AB  - Cortexillins I and II of D. discoideum constitute a novel subfamily of proteins
      with actin-binding sites of the alpha-actinin/spectrin type. The C-terminal
      halves of these dimeric proteins contain a heptad repeat domain by which the two
      subunits are joined to form a two-stranded, parallel coiled coil, giving rise to
      a 19 nm tail. The N-terminal domains that encompass a consensus actin-binding
      sequence are folded into globular heads. Cortexillin-linked actin filaments form
      preferentially anti-parallel bundles that associate into meshworks. Both
      cortexillins are enriched in the cortex of locomoting cells, primarily at the
      anterior and posterior ends. Elimination of the two isoforms by gene disruption
      gives rise to large, flattened cells with rugged boundaries, portions of which
      are often connected by thin cytoplasmic bridges. The double-mutant cells are
      multinucleate owing to a severe impairment of cytokinesis.

PMID- 8752218
TI  - The alpha(1,3)fucosyltransferase Fuc-TVII controls leukocyte trafficking through
      an essential role in L-, E-, and P-selectin ligand biosynthesis.
AB  - alpha(1,3)Fucosylated oligosaccharides represent components of leukocyte
      counterreceptors for E- and P-selectins and of L-selectin ligands expressed by
      lymph node high endothelial venules (HEV). The identity of the
      alpha(1,3)fucosyltransferase(s) required for their expression has been uncertain,
      as has a requirement for alpha(1,3)fucosylation in HEV L-selectin ligand
      activity. We demonstrate here that mice deficient in alpha(1,3)
      fucosyltransferase Fuc-TVII exhibit a leukocyte adhesion deficiency characterized
      by absent leukocyte E- and P-selectin ligand activity and deficient HEV L
      selectin ligand activity. Selectin ligand deficiency is distinguished by blood
      leukocytosis, impaired leukocyte extravasation in inflammation, and faulty
      lymphocyte homing. These observations demonstrate an essential role for Fuc-TVII
      in E-, P-, and L-selectin ligand biosynthesis and imply that this locus can
      control leukocyte trafficking in health and disease.

PMID- 8752219
TI  - An essential cytoskeletal linker protein connecting actin microfilaments to
      intermediate filaments.
AB  - Typified by rapid degeneration of sensory neurons, dystonia musculorum mice have
      a defective BPAG1 gene, known to be expressed in epidermis. We report a neuronal
      splice form, BPAG1n, which localizes to sensory axons. Both isoforms have a
      coiled-coil rod, followed by a carboxy domain that associates with intermediate
      filaments. However, the amino terminus of BPAG1n differs from BPAG1e in that it
      contains a functional actin-binding domain. In transfected cells, BPAG1n coaligns
      neurofilaments and microfilaments, establishing this as a cytoskeletal protein
      interconnecting actin and intermediate filament cytoskeletons. In BPAG1 null
      mice, axonal architecture is markedly perturbed, consistent with a failure to
      tether neurofilaments to the actin cytoskeleton and underscoring the
      physiological relevance of this protein.

PMID- 8752220
TI  - A deubiquitinating enzyme interacts with SIR4 and regulates silencing in S.
      cerevisiae.
AB  - The SIR2, SIR3, and SIR4 proteins are required for silencing of transcription at
      the silent mating type loci and at telomeres in yeast. Using protein affinity
      chromatography, we show that SIR2, SIR3, and two proteins of 69 and 110 kDa
      tightly associate with SIR4. Surprisingly, the 110 kDa SIR4-binding protein is
      identical to UBP3, one of several previously described yeast enzymes that
      deubiquitinate target proteins. Deletion of the UBP3 gene results in markedly
      improved silencing of genes inserted either near a telomere or at one of the
      silent mating type loci, indicating that UBP3 is an inhibitor of silencing. We
      discuss possible roles for UBP3 in controlling the activity or assembly of the
      SIR protein complex.

PMID- 8752222
TI  - Improving the use of contraceptives: the challenge continues.

PMID- 8752221
TI  - The invariant U5 snRNA loop 1 sequence is dispensable for the first catalytic
      step of pre-mRNA splicing in yeast.
AB  - We have developed an in vitro reconstitution system to investigate the role of U5
      snRNA in the two catalytic steps of pre-mRNA splicing. The invariant U5 loop 1 is
      known to interact with exon sequences at the 5' splice site before the first
      catalytic step. Remarkably, analysis of U5 mutations in vitro reveals that the
      first transesterification occurs accurately in the absence of the U5 loop.
      Therefore this sequence is not an essential component of the spliceosomal active
      site for the first catalytic step. The second catalytic step, although strongly
      dependent on the presence of a U5 loop to tether the exon 1 splicing
      intermediate, is surprisingly tolerant of mutations in the invariant sequence.

PMID- 8752223
TI  - Compliance with contraceptives and other treatments.
AB  - OBJECTIVE: To define some of the issues unique to compliance with oral
      contraceptives, and some comparisons with other preventive and therapeutic
      treatments. DATA SOURCES: Reports of compliance with medical treatment were used,
      with a focus on studies using microelectronic monitoring to assess compliance.
      Studies included the general population and a variety of demographically
      different groups. METHODS OF STUDY SELECTION: Twenty-nine studies of medication
      compliance (including surveys and clinical trials with specific interventions),
      across a broad range of medical disorders, were selected for comparison with
      reports of oral contraceptive compliance. TABULATION, INTEGRATION, AND RESULTS:
      Rates of compliance with contraceptive methods are low, but differ little from
      rates of compliance with other medical treatments. Several questions might be
      used to ascertain the likelihood that an individual is willing to use an oral
      contraceptive as prescribed (eg, willingness to take a daily pill, to return for
      follow-up, and to report adverse effects). CONCLUSIONS: Studies of a variety of
      medical disorders have shown that no consequence is so severe that all patients
      can be assumed to comply with the prescribed treatment plan. Inadequate
      compliance often diminishes treatment efficacy, which suggests the need for
      alternative methods that do not require daily compliance.

PMID- 8752224
TI  - How effective are contraceptives? The determination and measurement of pregnancy
      rates.
AB  - OBJECTIVES: To provide an overview of contraceptive effectiveness and its
      determinants as well as reasons for the gap between the actual and expected
      number of unplanned pregnancies for various categories of users; to provide some
      guidelines for more precise, consistent terminology and measurements for use in
      future research; and to provide specific counseling guidelines; using combined
      oral contraceptives (OCs) as the example. DATA SOURCES: Fifty-three articles on
      contraceptive effectiveness were reviewed, with a particular focus on pregnancy
      rates among OC users and the quality of use contributing to those rates.
      Definitions and measurement of contraceptive effectiveness, its components, and
      its determinants were examined and discrepancies explored. METHODS OF STUDY
      SELECTION: Papers discussed were selected because they had special relevance.
      Only a few of the papers discussed in this article were quantitative studies of
      contraceptive behavior and effectiveness. Others were review articles,
      discussions of the appropriate measurement of various components of
      effectiveness. Others provided conceptual frameworks for studying method
      effectiveness. All published studies of OC compliance were reviewed. TABULATION,
      INTEGRATION, AND RESULTS: Comparing the definitions and measurement of both
      compliance and effectiveness revealed important inconsistencies. However, some
      trends did emerge, and these papers did provide a framework for the following
      discussion. The findings were used to develop a more coherent set of definitions,
      measurement approaches, and counseling strategies. Characteristics of the user,
      the method, and the service delivery system all play a role in contraceptive
      effectiveness. However, it is the quality of use, ie, the user's own behavior,
      that is the immediate determinant of the effectiveness of any short-term
      contraceptive method. The mean pregnancy rate for better-than-average users is
      4%; for poorer-than-average users, it is 8%. CONCLUSIONS: The range of
      contraceptive effectiveness rates is closely associated with user
      characteristics. Oral contraceptive users need to know that their own chance of
      becoming pregnant will vary with their fecundability, when and how frequently
      they have sexual intercourse, and, especially, how consistently and correctly
      they take their pills. The likelihood that any one user will take OCs correctly
      and consistently also is associated with her life-style, socioeconomic status,
      age, and other factors. Further research is needed to determine how forgiving OCs
      are of various pill-taking errors, to determine the impact of dual method use
      (eg, OCs and condoms), and to assess the effects of user, method, and
      programmatic characteristics on correct and consistent use and, in turn, on
      effectiveness.

PMID- 8752225
TI  - Measuring contraceptive effectiveness: a conceptual framework.
AB  - We present a conceptual model that outlines the four measures of how well a
      contraceptive method works: 1) efficacy, 2) effectiveness, 3) perfect-use
      pregnancy rate, and 4) typical-use pregnancy rate. Moreover, we illustrate how
      four variables influence these measures: 1) capacity to conceive, 2) frequency
      and timing of intercourse, 3) degree of compliance, and 4) inherent protection of
      the method. Because of inter-individual as well as intra-individual variability
      of the first three variables, generalizing results from a contraceptive clinical
      trial to other populations is problematic. There is a hierarchy of
      generalizability of the four outcome measures, with the typical-use pregnancy
      rate the least generalizable but the easiest to measure, and efficacy the most
      generalizable but the most difficult to measure. These four variables should be
      considered in the design and analysis of future contraceptive clinical trials.
      Finally, this article illustrates why the terms "pregnancy rate" and "failure
      rate" are not synonymous and why we recommend that the latter term not be used.

PMID- 8752226
TI  - Physician-patient interaction in reproductive counseling.
AB  - OBJECTIVE: To review the scientific and clinical bases for effective patient
      counseling in contraceptive care. DATA SOURCES: All articles and chapters in the
      Annotated Bibliography of Doctor Patient Communication of the Task Force on
      Doctor and Patient of the American Academy on Physician and Patient were searched
      and included. This is an expert-derived data base based on MEDLINE review from
      1969 to 1994 and including expert-selected additions from PsychLit and a variety
      of other social science data bases, books, and reviews. METHODS OF STUDY
      SELECTION: Expert consensus was used from the Committee on Bibliography of the
      American Academy on Physician and Patient. TABULATION, INTEGRATION, AND RESULTS:
      The doctor-patient interaction is the main determinant of the accuracy and
      completeness of patient data, diagnostic accuracy, efficiency in the encounter,
      compliance, patient understanding of problems, and patient and physician
      satisfaction. Yet this critical skill is inadequately taught and practiced, with
      serious consequences for patient care and physician job satisfaction. Use of the
      14 structural elements (preparing the environment, preparing oneself,
      observation, greeting, introduction, detecting and overcoming barriers to
      communication, surveying problems, negotiating a priority problem, developing a
      narrative thread, establishing the life context of the patient, establishing a
      safety net, presenting findings and options, negotiating plans, and closing) and
      three functions (gathering information, developing a therapeutic relationship,
      and patient education) and their associated behaviors improves encounter results
      significantly. Other helpful activities are patient activation, facilitating
      partnership, review of findings and plans, eliciting and responding to patients'
      attitudes and emotions about contraception and fertility, and use of empathy and
      positive regard. CONCLUSIONS: The use of scientifically derived, empirically
      validated interview skills substantially improves outcomes in contraceptive and
      other patient education and counseling. Use of appropriate structure and
      functions of the encounter, patient participation and partnership, review of
      patient understanding and reactions, and relating to the patients' attitudes and
      emotions about the subject each improve the outcomes of contraceptive care.

PMID- 8752227
TI  - Through the patient's eyes: strategies toward more successful contraception.
AB  - OBJECTIVE: To review the literature focusing on studies of patient satisfaction
      and patient involvement in the design of care and to suggest strategies for
      involving patients effectively in their care. While addressing issues in
      contraception and adherence to contraceptive regimens, we write from the
      perspective of general physicians who manage patients with a broad variety of
      problems. By learning systematically what patients want, need, and experience in
      health and illness, we can use such information in the redesign and improvement
      of care. DATA SOURCES: Individual anecdote, focus groups of patients, patient
      survey data, and a literature review were used. METHODS OF STUDY SELECTION: The
      literature review used an English-language search of MEDLINE from 1970 to 1996,
      with search terms including patient satisfaction, consumer participation, patient
      participation, self-care, contraception, and contraceptive behavior. Previous
      studies conducted by the authors were also reviewed. TABULATION, INTEGRATION, AND
      RESULTS: Patients report that providers who solicit patients needs and
      preferences for involvement in decision making, who encourage family involvement,
      and who tailor educational efforts to the individual adult learning style of the
      patient engender greater patient satisfaction, adherence to recommended
      therapies, and improved patient outcomes. Recent trends in the United States,
      such as the growing use of alternative therapies, the self-help movement, and
      consumerism have influenced patient attitudes and behaviors toward seeking care
      and are changing their behavior. We discuss several strategies to improve patient
      involvement in their care, including the use of patient diaries and contracts,
      pre- and post-visit preparation and communication, the involvement of patients in
      educating providers, and the use of information technologies to enhance
      communication between patients and providers. CONCLUSIONS: Patient involvement in
      the redesign of care may help promote greater effectiveness of contraceptive
      strategies.

PMID- 8752228
TI  - Adolescents and the contraceptive pill: the impact of beliefs on intentions and
      use.
AB  - OBJECTIVES: To determine which beliefs about the contraceptive pill predict
      adolescent females' intentions to use the pill and their actual pill use, and to
      examine how intentions toward other birth control methods influence adolescents'
      intentions to use the pill and their eventual pill use. METHODS: Three hundred
      forty-five adolescents were interviewed about their beliefs regarding the
      consequences of using the pill and about their intentions to use the pill and
      other contraceptive methods. Follow-up interviews were conducted 1 year later,
      during which subjects reported their sexual activity and oral contraceptive use
      over the course of the year. RESULTS: Concerns about health and physical
      appearance differentiated subjects who intended to use the pill from those who
      did not, those who reported actually using the pill at all from those who did
      not, and those who did or did not use the pill consistently. The impact of
      beliefs differed between sexually active subjects and those who first had sex
      after the initial interview. Intentions to use withdrawal were negatively related
      to subjects' use of the pill (beta = -0.19, P < .05), although intentions to use
      condoms were unrelated to pill use. Intentions toward abortion were unrelated to
      either intentions to use the pill or eventual pill use. CONCLUSIONS: Female
      adolescents' beliefs about the contraceptive pill predicted their initial
      intentions to use the pill and their actual pill use over the course of a year.
      Adolescents may view withdrawal-although apparently not condoms-as an alternative
      to pill use. Abortion appears to be a backup to pill use rather than a
      substitute.

PMID- 8752229
TI  - Adolescent contraceptive behavior: the impact of the provider and the structure
      of clinic-based programs.
AB  - OBJECTIVE: To characterize general trends in research on the impact of provider
      variables on adolescent contraceptive behavior and to identify useful frameworks
      for designing clinic-based programs aimed at reducing unintended adolescent
      pregnancy. DATA SOURCES: A computerized search of Psychological Abstracts,
      Sociological Abstracts, and MEDLINE identified English-language articles from
      1990 to 1995 on adolescent contraceptive behavior in the United States. All
      relevant citations within these articles also were examined. METHODS OF STUDY
      SELECTION: Studies were selected that focused on any aspect of provider
      characteristics as they relate to adolescent contraceptive behavior. TABULATION,
      INTEGRATION, AND RESULTS: Based on a conceptual integration of the articles,
      three general research issues on provider characteristics were identified; 1) the
      effectiveness of adolescent-based clinic programs and provider variables that
      discriminate successful versus unsuccessful programs, 2) the effects of parental
      notification policies on adolescent clinic use, and 3) whether the presence of
      clinics promotes sexual activity on the part of adolescents. Issues that must be
      considered in the structuring of provider-based programs include the strategic
      focus of the program, the target behaviors, the target population, and the
      structuring of educational materials. CONCLUSION: The effectiveness of adolescent
      based clinic programs is mixed. Parental notification of adolescent use of a
      clinic can, in some cases, decrease the likelihood of clinic use. There is little
      convincing evidence that the presence of adolescent clinics promotes sexual
      activity.

PMID- 8752230
TI  - Factors affecting the consistent use of barrier methods of contraception.
AB  - OBJECTIVES: To discuss the major issues involved in the consistent and effective
      use of barrier methods of contraception. DATA SOURCES: Major research and review
      articles on barrier methods published within the last 10 years were considered.
      One major source of articles was Family Planning Perspectives. METHODS OF STUDY
      SELECTION: This paper is a focused review and integration of recent literature
      rather than a comprehensive literature review. Only selected articles published
      since 1986 that are pertinent to the issues raised are included. TABULATION,
      INTEGRATION, AND RESULTS: All barrier methods have common characteristics that
      influence their patterns of use. The correct and consistent use of such methods
      is determined by the complex interaction of characteristics of the methods
      themselves, characteristics of users, and the situational context. Method
      characteristics include the extent of interference with sexual spontaneity and
      enjoyment, the amount of partner cooperation required, and the ability of the
      method to protect against human immunodeficiency virus and other sexually
      transmitted diseases. User characteristics include motivation to avoid unintended
      pregnancy, ability to plan, comfort with sexuality, and previous contraceptive
      use. Stage of sexual career, relationship characteristics, and physical and
      sexual abuse are important situational influences. CONCLUSIONS: Even though most
      barrier methods can be obtained without a prescription from a provider,
      clinicians have an extremely important role in promoting effective and consistent
      method use. Four major ways to improve the use of barrier methods currently
      available include: 1) improve method characteristics and the distribution
      systems; 2) change consumers' perceptions of method attributes; 3) train
      consumers to use methods correctly and overcome-perceived negative
      characteristics of the methods; and 4) change values about the perceived
      importance of method characteristics. There also is an urgent need for the
      development of better barrier methods.

PMID- 8752231
TI  - Literacy and contraception: exploring the link.
AB  - OBJECTIVE: To describe what is known about the relation of literacy skills to
      contraceptive use and to suggest directions for future research. An overview of
      what is known about the literacy skills of Americans and the prevalence of
      inadequate functional health literacy is presented. Information about reading
      requirements for various methods of contraception and advice from health
      educators on dealing with low-literate populations are described. DATA SOURCES:
      MEDLINE, PsychInfo, and ERIC searches for the last 20 years were completed using
      the terms literacy, literacy and health, family planning, health status,
      educational status, risk factors, contraception, and pregnancy. METHODS OF STUDY
      SELECTION: The primary literature searches identified 125 articles. After
      reviewing abstracts for these articles, we excluded 79, because they contained no
      specific mention of literacy or educational status relating to contraception.
      TABULATION INTEGRATION, AND RESULTS: We were unable to identify and study
      specifically devoted to the relation between functional literacy and actual use
      of contraceptives. Forty-six with relevant background or related information were
      identified: literacy and health (19), adult literacy (nine), literacy and
      contraception (11), and literacy and family planning (seven). Over one-third of
      English-speaking and 62% of Spanish-speaking patients had inadequate or marginal
      functional health literacy in a study conducted at two urban public hospitals.
      Studies by health educators have demonstrated that information for many types of
      contraceptives is frequently above the patient's reading level. Available
      epidemiologic information on the relation between educational status and
      unplanned pregnancy is also presented. CONCLUSIONS: Although no study has
      specifically addressed how functional health literacy affects contraceptive use,
      it is reasonable to hypothesize that functional health literacy influences
      contraceptive knowledge, attitudes, and behaviors. Future research should focus
      on the relation between functional health literacy and actual use of various
      contraceptives.

PMID- 8752232
TI  - The effect of human immunodeficiency virus infection and drug use on birth
      characteristics.
AB  - OBJECTIVE: To explore the effect of human immunodeficiency virus (HIV) infection
      and drug use on birth weight, length, and gestational duration at delivery.
      METHODS: Subjects had a history of injection drug use or a sexual partner who was
      an injection drug user, were Scottish, and their HIV serostatus during pregnancy
      was known. Control pregnancies were matched for age, parity, ethnic group, year
      of delivery, and postal code sector of home address. In addition, some were
      matched for smoking and housing deprivation score. Birth weights were
      standardized for gestational age by expressing them as z scores with a mean of
      zero and a standard deviation of unity. Statistical analysis was by univariate
      and multiple regression with multilevel modeling. RESULTS: Regression analysis
      for birth weight, gestational age, and gestation-adjusted birth weights (z score)
      included 789 pregnancies in 693 women. Human immunodeficiency virus
      seropositivity was associated with a z score that was 0.27 lower (P = .03), but
      there was no significant difference in gestational duration at delivery. Current
      oral or injection drug use were associated with a reduction in standardized birth
      weight (z score -0.27, P = .06, and z score -0.28, P = .04, respectively), and
      injection drug use with a reduction in occipitofrontal circumference only (1.8 cm
      reduction, P = .05). Injection drug use, but not the other factors, had an effect
      on gestational age at delivery (1.54 weeks earlier, P < .001). CONCLUSION:
      Although HIV seropositivity is associated with a small reduction in standardized
      birth weight, this effect is less than that attributable to smoking and may not
      be of clinical significance. The effect seems to be associated with placental
      size. Opiate use, regardless of route, had a small association with reduced birth
      weight, suggesting a specific drug effect. However, only injection drug use had a
      strong association with early delivery, and this effect was likely to be
      clinically significant at the population level.

PMID- 8752233
TI  - The effects of maternal position and cardiac output on intrapulmonary shunt in
      normal third-trimester pregnancy.
AB  - OBJECTIVE: To assess the effect of pregnancy, maternal position, and cardiac
      output on intrapulmonary shunting (Qs/Qt) in normotensive nulliparous women near
      term. METHODS: Ten normotensive nulliparas between 36 and 38 weeks' gestation
      underwent pulmonary artery catheterization (via the subclavian route) and radial
      artery canalization. Baseline assessments were made with subjects in the left
      lateral recumbent position after a 30-minute stabilization period. Measurements
      were obtained sequentially in the left lateral, right lateral, supine, knee
      chest, sitting, and standing positions. Each position change was followed by a 10
      minute pre-measurement stabilization period. Cardiac output was measured via the
      thermodilution technique. Blood samples were obtained simultaneously from the
      pulmonary and radial arteries and analyzed in duplicate for oxygen content with a
      blood gas analyzer. Qs/Qt was calculated using the classic shunt equation.
      Statistical analysis was performed by analysis of variance of repeated measures
      of Qs/Qt and maternal position. The relationship of Qs/Qt to maternal cardiac
      output was evaluated by the correlation coefficient. Significance was defined as
      P < .05. RESULTS: Directly measured Qs/Qt averaged 15.3% in left lateral, 15.2%
      in right lateral, 13.9% in supine, 12.8% in knee-chest, 13.8% in sitting, and
      13.0% in standing positions. There was no statistically significant correlation
      between Qs/Qt and cardiac output (R2 = 0.11, not significant). CONCLUSION: This
      is the first report of directly measured Qs/Qt in normal pregnant women in the
      third trimester. Qs/Qt values reported in pregnancy are higher than those
      reported in nonpregnant individuals.

PMID- 8752234
TI  - Dose ranging study of the oxytocin antagonist atosiban in the treatment of
      preterm labor. Atosiban Study Group.
AB  - OBJECTIVE: To evaluate the minimal effective dose regimen of the oxytocin
      antagonist atosiban in the treatment of acute preterm labor and the effect of a
      bolus on uterine activity within the first 2 hours compared with no bolus and the
      same infusion rate. METHODS: A randomized, double-blind (except the ritodrine
      group), parallel group, multicenter study compared four different intravenous
      atosiban regimens (6.5 mg bolus plus 300 micrograms/minute, placebo bolus plus
      300 micrograms/minute, 2mg bolus plus 100 micrograms/minute, and 0.6 mg plus 30
      micrograms/minute) and intravenous ritodrine with respect to the cessation of
      uterine contractions for 1 hour or more during infusion, four or fewer
      contractions per hour in the last hour of therapy, and discontinuation because of
      adverse experiences. Three hundred two patients were enrolled. RESULTS: The
      lowest dose of atosiban (0.6 mg plus 30 micrograms/minute) was significantly less
      effective than ritodrine with respect to cessation of contractions and four or
      fewer contractions per hour in the last hour of therapy. Other atosiban regimens
      were comparable to ritodrine, except for the drug discontinuation rate for
      adverse experiences. Bolus therapy with high-dose atosiban resulted in a
      significantly greater proportion of patients who stopped contracting within the
      first 2 hours of treatment (17 of 63) compared with those not receiving a bolus
      (six of 58, P = .017). Because of adverse experiences, the study drug was
      discontinued in one of 244 atosiban patients and 15 of 58 ritodrine patients.
      CONCLUSION: Atosiban's effect on uterine activity in preterm labor was enhanced
      by bolus infusion and was similar to the effect of ritodrine, but with fewer side
      effects.

PMID- 8752235
TI  - Unexplained elevated maternal serum alpha-fetoprotein levels and pregnancy
      outcome in twins.
AB  - OBJECTIVE: To evaluate whether elevated maternal serum alpha-fetoprotein (MSAFP)
      levels in uncomplicated twin gestations are associated with an increased risk for
      pregnancy complications and adverse outcomes. METHODS: A retrospective data-base
      analysis was conducted of 267 women with twin pregnancies delivered between
      January 1988 and October 1994, of whom 42 had elevated MSAFP levels and 225 had
      normal levels. We evaluated rates of preterm delivery (defined as gestational age
      less than 34 weeks at delivery), birth weight less than 1500 g, twin-to-twin
      birth weight discordance, small for gestational age (SGA) infants (defined as
      birth weight below the tenth percentile for gestational age), and fetal
      malformations. Also assessed were potentially confounding variables such as
      obstetric and medical histories as well as sociodemographic factors. RESULTS:
      Among nulliparous women, an unexplained elevation in MSAFP levels was associated
      with a statistically significant increased risk for preterm delivery. Among
      multiparous women, this association is suggested by the data, but not
      significantly so. An unexplained elevation in MSAFP level was also associated
      with a significantly increased risk for birth weight less than 1500 g, but this
      was related to the increased rate of preterm births. No appreciably increased
      risk was apparent for SGA infants, fetal malformations (other than neural tube
      defects and abdominal wall defects), or twin-to-twin birth weight discordance.
      CONCLUSION: In twin pregnancies, an unexplained elevation in MSAFP level may
      increase the risk for preterm delivery but not other adverse pregnancy outcomes.

PMID- 8752236
TI  - Nasogastric enteral feeding in the management of hyperemesis gravidarum.
AB  - OBJECTIVE: To report our experience in treating hyperemesis gravidarum with
      nasogastric enteral feeding. METHODS: Seven women (ages 17-36 years, mean 27
      years) presented with intractable nausea, vomiting, dehydration, and weight loss
      (mean 13 lb) and were hospitalized for management of symptoms and nutritional
      support. An 8-Fr Dobbhoff nasogastric feeding tube was placed and nutritional
      supplement was administered as a continuous infusion, starting at a rate of 25
      mL/hour. The rate of infusion was increased in an incremental fashion until daily
      caloric requirements were met. RESULTS: Nausea and vomiting improved within 24
      hours after nasogastric tube placement. Enteral feedings were well tolerated, and
      all patients were discharged from the hospital within 8 days. Enteral feedings
      were continued, in an outpatient setting, for a mean of 43 days (range 5-174).
      Ultimately, all patients resumed oral feeding and discontinued enteral feeding.
      Subsequently, all patients gave birth to full-term, normal-weight babies.
      CONCLUSION: Enteral feeding via nasogastric tube seems to be effective in
      relieving intractable nausea and vomiting and in providing adequate nutritional
      support. Enteral nutrition should be considered as an alternative to total
      parenteral nutrition in the management of hyperemesis gravidarum.

PMID- 8752237
TI  - Third-trimester arterial blood gas and acid base values in normal pregnancy at
      moderate altitude.
AB  - OBJECTIVE: To report arterial blood gas and acid base values of normal
      nulliparous patients at moderate altitude for commonly used maternal positions.
      METHODS: Ten normotensive nulliparous women between 36 and 38 weeks' gestation
      volunteered to undergo radial and pulmonary artery cannulation as part of a
      larger study. Following instrumentation, baseline assessments were made in the
      left lateral recumbent position after a 30-minute stabilization period.
      Sequential measurements were then obtained in the left lateral, right lateral,
      supine, knee-chest, sitting, and standing positions. Blood samples were analyzed
      in duplicate for oxygen content on a blood gas analyzer. Statistical analysis was
      performed by analysis of variance of repeated measures with significance defined
      at P < or = .05. RESULTS: There was no significant difference in arterial blood
      gas or acid base values between any positions in this antepartum population of
      term healthy women. The composite mean values were as follows: pH 7.46, arterial
      carbon dioxide pressure (PaCO2) 26.6 mmHg, arterial oxygen pressure 88.3 mmHg,
      bicarbonate 18.2 mEq/L, saturated arterial hemoglobin level 0.96. CONCLUSION:
      Arterial blood gas and acid base values are not altered by maternal position in
      the late third trimester of pregnancy. The PaO2 in these women studied at
      moderate altitude was lower than previously reported for healthy pregnant women
      studied at sea level. Appropriate interpretation of arterial blood specimens of
      pregnant women should take into account both the pregnancy and altitude at which
      the women reside.

PMID- 8752239
TI  - Preterm delivery and perinatal death among black and white infants in a Chicago
      area perinatal registry.
AB  - OBJECTIVE: To explore associations between race, preterm delivery, etiologic
      classification of preterm delivery, and perinatal mortality. METHODS: The study
      population consisted of 13,010 black and 19,007 white mother-infant pairs
      delivered at Chicago-area hospitals in 1988-1989 categorized as term or preterm
      births. Preterm births were further divided by severity and etiology. Black-white
      differences in perinatal mortality within groups were calculated and adjusted for
      birth weight and other potential confounding variables. RESULTS: Black women were
      nearly twice as likely as whites to experience preterm (before 37 weeks'
      gestation) and very preterm (before 32 weeks' gestation) delivery associated with
      premature rupture of membranes (PROM) or classified as idiopathic. Although black
      infants were also found to have twice the perinatal mortality risk of white
      infants (relative risk [RR] 2.1, 95% confidence interval [CI] 1.7-2.5), the
      overall preterm perinatal mortality rates did not differ between black and white
      women (RR 1.0, 95% CI 0.8-1.2). However, among preterm births, perinatal
      mortality was not uniform within categories of medical etiology. The mortality
      risk was the same for black and white infants born preterm following
      polyhydramnios or placental complications (RR 1.1, 95% CI 0.6-1.9), the same for
      black and white infants born preterm after labor induction (RR 1.1, 95% CI 0.6
      1.9), and higher for black infants classified as idiopathic preterm deliveries
      (RR 1.6, 95% CI 1.1-2.3). In contrast, mortality rates tended to be lower for
      black infants born preterm following PROM-amnionitis (RR 0.8, 95% CI 0.5-1.2).
      The idiopathic disparity was explained by a differential birth weight
      distribution (adjusted RR 1.1, 95% CI 0.7-1.9); however, the apparent survival
      benefit among black infants born preterm following PROM increased even further
      after adjustment for birth weight (adjusted RR 0.4, 95% CI 0.2-0.7). CONCLUSION:
      Black infants born preterm after PROM appear to have a survival advantage
      compared with their white counterparts, an effect not observed within other
      etiologic categories of preterm delivery.

PMID- 8752238
TI  - Latent labor with an unknown uterine scar.
AB  - OBJECTIVE: To determine if avoiding the augmentation of ineffective contractions
      in women with unknown uterine scars would decrease the risk of cesarean for
      protraction disorders, compared with awaiting the onset of spontaneous labor.
      METHODS: Term gravidas with one or two unknown uterine scars in early labor were
      randomized to nonintervention (N = 101) and intervention (N = 96) groups.
      Nonintervention subjects were discharged if cervical change did not occur within
      4 hours. Intervention subjects were admitted. Contractions that persisted for 4
      hours without cervical change were augmented with oxytocin. RESULTS: Intervention
      subjects received oxytocin significantly more often (82 versus 55%, P < .001) and
      had a statistically significantly higher rate of uterine scar separation (5
      versus 0%, P = .03). There was no difference between the two groups in length of
      active labor (4.0 versus 4.25 hours) or incidence of cesarean delivery (16 versus
      17%). CONCLUSION: The augmentation of ineffective contractions during latent
      labor in gravidas with an unknown uterine scar does not increase the rate of
      cesarean delivery, but it is significantly more likely to result in uterine scar
      separations.

PMID- 8752240
TI  - The nonreactive nonstress test: predictive value for neonatal anemia in the
      isoimmunized pregnancy.
AB  - OBJECTIVE: To assess the value of the fetal nonstress test (NST) in predicting
      neonatal transfusion in pregnancies complicated by red cell isoimmunization.
      METHODS: We retrospectively reviewed the records of all patients evaluated for
      isoimmunization in pregnancy for the period January 1992 to December 1994. In
      addition to prenatal care, serial ultrasonography, and invasive testing when
      indicated, patients had NSTs two times per week. Nonstress tests were interpreted
      as either reactive or nonreactive using standard criteria. Results of the last
      NST before delivery were analyzed. Neonatal outcome data were obtained
      prospectively and by chart review. RESULTS: Sixty patients with isoimmunization
      were identified during the study period. Fifty-one patients (85%) had reactive
      NSTs until delivery, and nine (15%) had nonreactive NSTs that prompted delivery.
      Twelve of 51 (23.5%) patients with reactive NSTs and seven of nine (77.8%)
      patients with nonreactive NSTs required neonatal transfusion (P = .003, odds
      ratio 11.4 [95% confidence interval (CI) 1.7-120.2]). The mean (standard error of
      the mean; range) hematocrit (%) at birth was 38.9 (3.0; 21.3-52.0) in patients
      with reactive NSTs and 28.3 (3.8; 14.5-45.0) in those with nonreactive NSTs (P <
      .05). A nonreactive NST had a 77.8% positive predictive value (95% CI 49.0-100)
      in identifying the need for neonatal transfusion. CONCLUSION: These findings
      indicate that a nonreactive NST is predictive of subsequent neonatal transfusion
      in patients with isoimmunization. The antepartum fetal NST is a useful adjunct in
      the management of isoimmunized pregnancies.

PMID- 8752241
TI  - Hyperechogenic fetal bowel and elevated serum alpha-fetoprotein: a poor fetal
      prognosis.
AB  - OBJECTIVE: To evaluate the clinical significance of increased fetal bowel
      echogenicity in women with elevated maternal serum alpha-fetoprotein (MSAFP)
      during the second trimester. METHODS: The study group comprised six pregnant
      women with elevated second-trimester MSAFP (greater than 2.5 multiples of the
      median), whose ultrasonographic evaluations indicated hyperechogenic fetal bowel.
      They were compared with six pregnant women whose fetuses, during routine second
      trimester ultrasonographic screening for fetal anomalies, were found to have a
      hyperechogenic bowel without elevated MSAFP, according to natural history,
      pregnancy outcome, and associated features. RESULTS: All six fetuses with the
      combination of elevated MSAFP and echogenic bowel were growth-restricted; four
      died in utero and one of the two live-born infants died during the neonatal
      period. The single survivor in this group was born prematurely; necrotizing
      enterocolitis was diagnosed at 30 days of life and surgery was performed. None of
      the cases had associated congenital anomalies. Only one of the six controls had
      associated anomalies (trisomy 21), and this pregnancy was terminated. The
      pregnancy course of the remaining five fetuses was normal; all were appropriate
      for gestational age and were delivered at term. No perinatal mortality occurred
      in this group; however, in one infant, cerebral palsy was diagnosed at 10 months
      of age. CONCLUSION: Fetal bowel hyperechogenicity found in women with elevated
      second-trimester MSAFP levels is associated with poor fetal outcome, particularly
      fetal growth restriction with fetal and neonatal death, and should be considered
      an ominous prenatal finding.

PMID- 8752242
TI  - Three-dimensional ultrasound in the evaluation of fetal head and spine anomalies.
AB  - OBJECTIVE: To test the application of three-dimensional (3-D) ultrasound for the
      antenatal diagnosis of fetal head and spinal anomalies. METHODS: Twenty-five
      fetuses with head or spinal anomalies and ranging in gestational age from 16 to
      33 weeks were studied prospectively: 11 with a control nervous system anomaly
      (neural tube defect [n = 4], encephalocele [n = 2], hydrocephalus [n = 4], and
      anencephaly [n = 1]), 13 fetuses with a family history or suspicion of cleft lip
      or palate, and one with a cloverleaf skull malformation. A volume scan was
      performed after the two-dimensional examination was complete. The mechanical
      transducer scans up to 40 degrees in less than 4 seconds, acquiring the data for
      a pyramid-shaped tissue volume. Three matched and dynamically linked images
      representing the X, Y, and Z planes are displayed simultaneously. When one image
      is manipulated, the remaining images are updated automatically to maintain a 90
      degrees difference. After the ideal three orthogonal planes are identified, a 3-D
      image can be reconstructed. A variable number of scan images are possible,
      depending on the volume size and the data acquisition time. Processing time for
      the reconstruction depends on volume size, the number of scan images included,
      and the degrees of rotation of the final image. RESULTS: The three orthogonal
      planes proved most helpful delineating the exact nature and anatomic level of the
      defect. No examination was delayed or required repetition because of suboptimal
      fetal positioning. The enhanced confidence achieved by our being able to
      delineate the precise anatomic level and extent of the defect improved patient
      counseling. The 3-D reconstructions clarified and documented the true magnitude
      of the defects and on occasion allowed a diagnosis not possible by either two
      dimensional or nonreconstructed 3-D imaging. CONCLUSION: Our experience with 3-D
      ultrasound suggests that it is an advance in high-quality ultrasound. Its
      greatest advantage is that it allows the user to view simultaneously the three
      orthogonal planes.

PMID- 8752243
TI  - A prospective study of the association between isolated fetal pyelectasis and
      chromosomal abnormality.
AB  - OBJECTIVE: To determine the incidence of chromosomal abnormalities among fetuses
      with isolated pyelectasis. METHODS: Between March 1991 and March 1994, 121 cases
      of isolated fetal pyelectasis were identified at our institution. Pyelectasis was
      defined as a renal pelvis anteroposterior diameter of at least 4 mm before 33
      weeks' gestation, and at least 7 mm at 33 weeks or thereafter. Once identified,
      women were offered antenatal genetic testing; if they declined, consent was
      sought for umbilical cord blood studies at delivery. RESULTS: Chromosomal
      evaluation was available in 99 women. Two chromosomal abnormalities were
      identified: one trisomy 21 and one mosaic 46, XY/47, XYY. The ages of the women
      were 32 and 28 years, respectively. Calculation of adjusted risks for Down
      syndrome and all chromosomal abnormalities indicated a 3.9-fold increase in Down
      syndrome risk and a 3.3-fold increase in risk for all chromosomal abnormalities
      in the presence of isolated fetal pyelectasis. CONCLUSION: Isolated fetal
      pyelectasis is associated with increased risk, over that related to age, for both
      Down syndrome and all chromosomal abnormalities. These factors may be valuable in
      counseling individual patients regarding the appropriateness of amniocentesis.

PMID- 8752244
TI  - Acetic acid visualization of the cervix: an alternative to cytologic screening.
AB  - OBJECTIVE: To investigate the value of acetic acid visualization of the cervix as
      an alternative to cytologic screening. METHODS: A prospective study was conducted
      in a squatter area in Cape Town, South Africa, on 2426 women who underwent
      speculum examination, naked-eye inspection of the cervix after application of
      acetic acid, and cytologic smear. The smears were stained and processed at the
      screening site. Patients with a positive reading after acetic acid or a smear
      indicating a high-grade squamous intraepithelial lesion (SIL) were referred for
      immediate colposcopy, biopsy, and when indicated, treatment by large loop
      excision of the transformation zone. Therefore, histology was obtained on all
      patients with a positive acetic acid test or a positive cytology. RESULTS:
      Seventy-six women with positive reactions to acetic acid. Among the 2350 women
      with negative reactions, 254 had positive cervical smears; only 11 of these had
      histologic high-grade SIL. In contrast, 20 of the 61 women with positive cytology
      and positive acetic acid test had high-grade SIL on histology. Therefore, the
      acetic acid reaction enabled the observer to detect 20 of the 31 women (64%) who
      exhibited a high-grade SIL both on cytology and histology. CONCLUSION: In
      locations where access to cytopathology is limited, naked-eye visualization of
      the cervix after application of diluted acetic acid warrants consideration as an
      alternative in the detection of cervical premalignant lesions.

PMID- 8752245
TI  - Ovarian cancer incidence (1989-1991) and mortality (1954-1993) in The
      Netherlands.
AB  - OBJECTIVE: To examine ovarian cancer incidence and mortality in the Netherlands,
      and to relate trends in mortality to changes in parity and use of oral
      contraceptives. METHODS: Age-standardized and age-specific incidence and
      mortality rates are presented using incidence data from the Netherlands Cancer
      Registry, 1989-1991, and mortality data from the Netherlands Central Bureau of
      Statistics, 1954-1993. RESULTS: In the period 1989-1991, age-standardized
      incidence of ovarian cancer was 14.9 per 10(5) woman-years. The majority (89%) of
      these tumors had an epithelial origin. Two-thirds of all newly diagnosed ovarian
      cancers already showed extension to the pelvis or beyond at diagnosis. From the
      period 1954-1958 to 1969-1973, age-standardized mortality rates increased from
      10.6 to 13.1 per 10(5) woman-years. Thereafter, a decline was noted to 11.4 per
      10(5) woman-years in the period 1989-1993. Age-specific mortality rates showed a
      pattern of rising mortality in the elderly, whereas mortality in the younger age
      categories was declining. The number of live births has declined gradually, and
      oral contraceptive use has increased. CONCLUSION: Incidence of ovarian cancer is
      high in the Netherlands, but comparable to other countries in north-western
      Europe and North America. Mortality rates are rising in the elderly and declining
      in the young. Further research is needed concerning the effects of oral
      contraceptives, fertility drugs, and hormone replacement therapy on the incidence
      and mortality of ovarian cancer.

PMID- 8752246
TI  - Prognostic significance of gross myometrial invasion with endometrial cancer.
AB  - OBJECTIVE: To determine if intraoperative estimation of gross myometrial invasion
      is sufficiently precise to guide surgical aggressiveness in staging patients with
      endometrial cancer. METHODS: Between September 1987 and September 1995, 236 women
      with endometrial cancer had visual estimation of gross myometrial invasion during
      surgical staging which included pelvic and para-aortic lymphadenectomy. RESULTS:
      In 213 patients (90.3%), the depth of gross myometrial invasion correctly
      predicted the microscopic depth of invasion on permanent histopathologic
      sections. Statistically significant associations were found between gross depth
      of myometrial invasion and tumor grade (P < .001), histopathology (P = .014),
      cervical metastases (P < .001), adnexal metastases (P < .001), omental metastases
      (P < .001), malignant pelvic cytology (P < .001), pelvic lymph node metastases (P
      < .001), para-aortic lymph node metastases (P = .001), and surgical stage (P <
      .001). Patients with more than 50% gross myometrial invasion were more likely to
      have poorly differentiated malignancies; nonendometrial histologies; malignant
      pelvic cytology; higher surgical stage; and cervical, adnexal, omental, pelvic
      lymph node, and para-aortic lymph node metastases. Patients with more than 50%
      gross myometrial invasion had a 6.4-fold higher prevalence of pelvic lymph node
      metastases, a 6.9-fold higher prevalence of para-aortic lymph node metastases,
      and a 6.7-fold higher prevalence of advanced surgical stage than patients with
      less than 50% myometrial invasion. CONCLUSION: Patients with endometrial cancer
      and more than 50% myometrial invasion on gross visual intraoperative estimation
      are at marked risk for extrauterine metastases, including pelvic and para-aortic
      lymph node metastases. Such patients should be considered for more aggressive
      surgical staging, including pelvic and para-aortic lymphadenectomy.

PMID- 8752247
TI  - A randomized controlled trial of postoperative nasogastric tube decompression in
      gynecologic oncology patients undergoing intra-abdominal surgery.
AB  - OBJECTIVE: To evaluate the effect of nasogastric decompression after extensive
      intra-abdominal surgery in gynecologic oncology patients. METHODS: Over a 1-year
      period, 110 gynecologic oncology patients undergoing extensive intra-abdominal
      surgery were enrolled in a randomized controlled trial of postoperative
      nasogastric tube versus intra-operative orogastric tube decompression. RESULTS:
      The nasogastric and orogastric groups were similar in age, case distribution,
      surgery length, and blood loss. The nasogastric group had significantly longer
      times to first passage of flatus and tolerance of a clear liquid diet than did
      the orogastric group. However, both groups were similar in time to tolerance of a
      regular diet and hospital stay. On average, the nasogastric tube was maintained
      for 3.2 +/- 2.1 days (range 1-8) after surgery. The average daily nasogastric
      output was 440 +/- 283 mL (range 68-1565). No patient in the orogastric group
      required a nasogastric tube postoperatively, but one patient in the nasogastric
      group had a nasogastric tube reinserted for recurrent nausea and vomiting. Use of
      a nasogastric tube led to significantly more subjective complaints, eg, ear pain,
      painful swallowing, and nasal soreness, but did not significantly reduce the
      incidence of abdominal distention or nausea and vomiting. Major complications,
      eg, pneumonia, atelectasis, gastrointestinal bleeding, and wound breakdown or
      infection, occurred equally in both groups. However, the incidence of febrile
      morbidity was significantly greater in the nasogastric group. There were no known
      anastamotic complications or aspirations in either group. Postoperative changes
      in hematological indices and electrolytes were comparable in both groups.
      CONCLUSION: Postoperative nasogastric tube decompression in gynecologic oncology
      patients undergoing extensive intra-abdominal surgery does not appear to provide
      any substantial benefit but significantly increases patient discomfort. As a
      result of this study, we have eliminated postoperative nasogastric decompression
      except in highly selected circumstances, such as extensive bowel surgery in
      patients with prior irradiation or substantial edema from bowel obstruction.

PMID- 8752249
TI  - The effect of knot geometry on the strength of laparoscopic slip knots.
AB  - OBJECTIVE: To evaluate and compare the strength of six different knot geometries
      used in laparoscopic slip knots. METHODS: The strength of six extracorporeal slip
      knots used in laparoscopic surgery was measured using a tensiometer. Two multiple
      throw laparoscopic square knots (the intracorporeal two-turn flat square knot and
      the extracorporeal sliding square knot) were used as controls. Each knot type was
      tied five times, and each type was tied in random order by the same primary and
      assisting surgeons using a laparoscopic pelvic surgery training model. One-way
      analysis of variance was performed to detect significant differences in knot
      strengths, and the variability in knot strength for each knot type was determined
      by Tukey's multiple comparison test. RESULTS: A statistically significant effect
      for knot geometry was identified. The mean knot strengths +/- standard deviation
      (SD), measured in newtons, from strongest to weakest, were: 4S knot (28.01 +/-
      11.45), fisherman's knot (22.45 +/- 6.89), modified Roeder knot (19.86 +/- 9.30),
      Roeder knot (15.77 +/- 7.02), Weston knot (7.28 +/- 7.96), and Duncan knot (6.55
      +/- 0.95). The mean knot strengths for the multiple-throw control square knots
      were as follows: intracorporeal two-turn flat square knot (41.21 +/- 2.69) and
      extracorporeal sliding square knot (27.81 +/- 16.27). The intracorporeal two-turn
      flat square knot (control) was significantly stronger (P < .05) than all slip
      knots except the 4S and fisherman's knot. CONCLUSION: The 4S and fisherman's
      knots are the strongest laparoscopic slip knots and are the only slip knots
      similar in strength to multiple-throw square knots.

PMID- 8752248
TI  - Tumor markers and transvaginal ultrasonography in the diagnosis of endometrioma.
AB  - OBJECTIVE: To evaluate the accuracy of CA 19.9 plasma levels (with or without CA
      125 levels) combined with transvaginal ultrasonography in the differential
      diagnosis of endometrioma. METHODS: One hundred eighteen consecutive
      premenopausal nonpregnant women had laparoscopy or laparotomy between November
      1994 and November 1995 because of the presence of a persistent adnexal mass. They
      underwent transvaginal ultrasonography and measurement of CA 19.9 and CA 125
      plasma levels within 2 days before surgery. The ultrasonographic impression and
      the tumor marker values were compared with the histopathologic diagnosis. The
      overall agreement between the test result and the actual outcome was calculated
      using the kappa statistic. RESULTS: Transvaginal ultrasonography had a strong
      agreement between test result and surgery (kappa value 0.84), whereas the
      combined methods were associated with a lower kappa value (range 0.24-0.80).
      CONCLUSION: Transvaginal ultrasonography used alone is the most cost-effective
      method in the preoperative differential diagnosis of endometrioma.

PMID- 8752250
TI  - Abortion at 18-22 weeks by laminaria dilation and evacuation.
AB  - OBJECTIVE: To evaluate the complications of late second-trimester abortions (18
      22 weeks) by laminaria dilation and evacuation, and the obstetric outcome of
      subsequent pregnancies. METHODS: Dilation of the cervix was achieved by repeated
      laminaria tent replacement. Evacuation was carried out in the outpatient clinic
      using general anesthesia. After the first menstrual period, all patients were
      invited for examination and thereafter were asked to report the outcome of
      subsequent pregnancies. RESULTS: One hundred seventy-one late second-trimester
      abortions were performed. Cervical dilation was satisfactory in 158 women (92%).
      Operative sonography was required in nine (5%) women. One had uterine atony.
      Follow-up from 150 (88%) women indicated no infection, but one woman required
      repeat curettage for retained products of conception. There was no indication of
      cervical injury on cervical internal os measurements remote from abortion. Of the
      50 patients who conceived and elected to continue the subsequent pregnancies, two
      had premature deliveries unrelated to cervical incompetence, and all others
      reached term. CONCLUSION: Late second-trimester termination by laminaria dilation
      and evacuation is safe and probably not associated with future adverse pregnancy
      outcome.

PMID- 8752251
TI  - Relative morbidity of abdominal hysterectomy and myomectomy for management of
      uterine leiomyomas.
AB  - OBJECTIVE: To compare the morbidity of total abdominal hysterectomy and abdominal
      myomectomy in the surgical management of uterine leiomyomas. METHODS: Hospital
      records were reviewed for all women who underwent hysterectomy (n = 89) or
      myomectomy (n = 103) between May 1, 1988, and May 1, 1993, for the preoperative
      diagnosis of leiomyoma. RESULTS: There were significant differences between the
      two groups for average age (hysterectomy 39.2 years, myomectomy 34.4 years; mean
      difference 4.8, 95% confidence interval [CI] of difference 3.7-5.9), uterine size
      (hysterectomy 15.2, myomectomy 11.5 weeks; mean difference 3.8, 95% CI of
      difference 2.0-5.4) and use of a GnRH agonist (hysterectomy 23.6%, myomectomy
      55.3%; relative risk [RR] 0.4, 95% CI 0.3-0.6). Myomectomy was associated with
      decreased estimated blood loss (hysterectomy 796 mL, myomectomy 464 mL; mean
      difference 331, 95% CI 121-542) and febrile morbidity (risk of temperature 38C or
      48 or more hours postoperatively: for hysterectomy 49.4%, for myomectomy 32%; RR
      1.5, 95% CI 1.1-2.2). Using multivariate linear regression, estimated blood loss
      was similar between the groups after controlling for uterine size. There was no
      difference in blood transfusion rates. There were two ureteral, one bladder, one
      bowel, and one femoral nerve injury in the hysterectomy group, and there were no
      intraoperative visceral injuries in the myomectomy group. CONCLUSION: Myomectomy
      compares favorably to hysterectomy in the surgical management of leiomyomas, with
      a possible decreased risk for visceral injury and infection.

PMID- 8752253
TI  - Cost analysis of shared oocyte in vitro fertilization.
AB  - OBJECTIVE: To estimate the cost per woman delivered of a shared oocyte in an in
      vitro fertilization (IVF) program, and to compare these costs with those of a
      routine IVF program. METHODS: The cost of 23 shared oocyte cycles was analyzed
      retrospectively and compared with the cost of routine IVF. RESULTS: The cost per
      woman delivered in the shared oocyte program was approximately $22,000, compared
      with $66,000 in the routine IVF program. CONCLUSION: Shared IVF is a very cost
      effective program and others donors and recipients an otherwise unavailable
      opportunity.

PMID- 8752252
TI  - Soluble tumor necrosis factor receptors and interleukin-6 levels in patients with
      severe preeclampsia.
AB  - OBJECTIVE: To investigate whether serum and amniotic fluid (AF) levels of soluble
      tumor necrosis factor receptors and interleukin-6, markers of immune activation
      and endothelial dysfunction, are altered in patients with severe preeclampsia.
      METHODS: Plasma was collected before induction of labor, at delivery, and
      postpartum from 19 patients with severe preeclampsia. Amniotic fluid was also
      obtained in early labor from these patients. Similar samples were obtained from
      an antepartum control group matched for gestational age and a term control group
      without preeclampsia. All plasma and AF samples were assayed for p55 and p75
      soluble tumor necrosis factor receptors and for interleukin-6 by specific enzyme
      linked immunoassays. Levels in preeclamptic patients and the control groups were
      compared. RESULTS: Levels of both receptors were significantly elevated in AF and
      all maternal plasma samples except those collected 24 hours postpartum for
      patients with preeclampsia relative to levels in controls. Interleukin-6 was
      detected more frequently and in higher concentrations in the plasma collected
      before labor for preeclamptic patients compared with controls, but no difference
      was noted in interleukin-6 detection rates or plasma concentrations at delivery.
      Conversely, AF concentrations of interleukin-6 were significantly reduced in
      patients with preeclampsia. CONCLUSION: The increased levels of soluble tumor
      necrosis factor receptors found in patients with severe preeclampsia may
      represent a protective response to increased tumor necrosis factor activity and
      be a marker for immune activation. Increased interleukin-6 concentrations in
      maternal plasma before labor suggest the involvement of this cytokine as well in
      the altered immune response and its contribution to endothelial cell dysfunction.

PMID- 8752254
TI  - Continuous and cyclical clodronate therapies and bone density in postmenopausal
      bone loss.
AB  - OBJECTIVE: To evaluate the effectiveness of different clodronate regimens in
      postmenopausal osteoporosis. METHODS: In groups of 20, 60 women were randomly
      assigned to one of three treatments: oral calcium, 1000 mg/day; oral calcium plus
      oral clodronate, 400 mg/day; oral calcium plus oral clodronate, 400 mg/day for 30
      days, followed by a 60-day period of calcium supplement alone. This last regimen
      was repeated four times in the 12-month study period. RESULTS: Patients who
      received calcium alone showed a decline in spinal bone mass, both after 6 and 12
      months (P < .03 and P < .005, respectively); femoral density in this group also
      decreased after 6 and 12 months (P < .002 and P < .05, respectively). On the
      other hand, both clodronate-treated groups had increased levels of lumbar bone
      mass compared with controls, both after 6 and 12 months of therapy. However, at
      the end of the study, patients treated with cyclical clodronate had higher spinal
      bone mass compared with those treated continuously (3.32 +/- 0.71 versus 0.43 +/-
      0.89%, P < .02). After 6 months, femoral bone density was significantly higher
      both in subjects treated with clodronate, both cyclically and continuously (P <
      .01), compared with controls. Continuous clodronate treatment resulted in a clear
      fall in biochemical indices of bone resorption, together with a consequent
      decrease in osteocalcin at 6 (P < .02) and 12 months (P < .003) and a significant
      increase in parathyroid hormone after 12 months (P < .001) of therapy.
      CONCLUSION: One-year treatment with clodronate induces a gain in bone mass,
      especially in the spine. The continuous regimen does not result in any further
      benefit in lumbar bone density over the cyclical one, probably because of a
      greater suppression of bone turnover.

PMID- 8752255
TI  - Hot flushes, menstrual status, and hormone levels in a population-based sample of
      midlife women.
AB  - OBJECTIVE: To determine the frequency of hot flushes in a population sample of
      453 pre-, peri-, and postmenopausal women (aged 48-59 years), and to investigate
      the relationship of hot-flush reporting with menstrual status, serum levels of
      estradiol (E2), inhibin, and FSH, history of premenstrual complaints, and
      physical and life-style factors. METHODS: We used a population-based sample.
      Interviews were conducted in the women's homes. RESULTS: Frequency of hot-flush
      reporting was associated with menstrual status (P < .001). Twenty-nine percent of
      women who had more than 3 and less than 12 months of amenorrhea, and 37% of
      postmenopausal women experienced hot flushes several times a day. In total, 13%
      of premenopausal women, 37% of perimenopausal women, 62% of postmenopausal women,
      and 15% of women on hormone therapy reported having had at least one hot flush in
      the previous 2 weeks. Follicle-stimulating hormone levels were higher in women
      who experienced hot flushes at least once a day or more (P < .001); E2 levels
      were higher in women experiencing one or no hot flushes per week (P < .001). The
      women in the perimenopausal group who experienced hot flushes had higher FSH
      levels (P = .008) and were more likely to have reported premenstrual complaints
      at the first interview 3 years earlier (P = .03). In the postmenopausal group,
      there was no significant difference with any of the variables studied between the
      women who were experiencing hot flushes and those who were not. CONCLUSION:
      Reporting of hot flushes is greatest 3 months or more after the final menstrual
      period. The frequency of hot flushes is associated with increasing FSH,
      decreasing E2, and a history of premenstrual complaints.

PMID- 8752256
TI  - Access to physicians, obstetric care use, and adequacy of prenatal care for
      Medicaid patients in Maine: 1985-1989.
AB  - OBJECTIVE: To document trends in prenatal care utilization and provider
      participation in the Maine Medicaid program for the period 1985-1989, and to
      examine the effect of physician availability on adequacy of care. METHODS: Five
      years of Medicaid claims data and 3 years of claims data linked to birth
      certificates were analyzed. RESULTS: Large decreases in overall physician
      participation in the Medicaid program were due to reductions in the number of
      family physicians and general practitioners, whereas the number of obstetricians
      increased during this time. Large increases in provider caseloads resulted from
      an increase in recipient enrollment. The number of prenatal visits per patient, a
      measure of access, increased during this time. Adequacy of care was not
      associated with physician availability after controlling for maternal age,
      maternal education, out-migration for care, and type of location (rural versus
      urban). Important differences by type of location that emerged included less
      physician availability in rural areas but a higher likelihood of receiving
      adequate care. Women from low-availability areas were more likely to seek care
      outside of their primary care area of residence. Women living in rural areas who
      out-migrated for care were not more likely to receive inadequate prenatal care.
      CONCLUSION: Access to prenatal care for Medicaid recipients may have increased
      from 1985 to 1989 despite decreased overall physician participation in the
      program, perhaps because of more participating obstetricians. In addition,
      adequacy of care was not associated with physician availability in this
      population. Women residing in rural areas experienced lower physician
      availability and greater out-migration for care with no adverse effect on
      adequacy of prenatal care.

PMID- 8752257
TI  - Uterine allergy: a cause of preterm birth?
AB  - OBJECTIVE: To identify the origin of eosinophils in cases of eosinophil
      associated preterm delivery. METHODS: From an established set of 465 consecutive
      non-anomalous singleton infants delivered at 22-32 weeks' gestation, we retrieved
      161 cases of preterm delivery following spontaneous onset of preterm labor, 78
      cases with maternal preeclampsia, 33 cases of abruption, and 193 cases of
      premature rupture of membranes (PROM). Charts were reviewed, and the placenta,
      umbilical cord, and membranes were examined histologically. In cases with
      extravascular eosinophils showing evident gradient toward the amniotic cavity,
      the origin of the eosinophils (fetal or maternal) was determined by the proximity
      to fetal or maternal vessels. RESULTS: Histologic evidence of an eosinophilic
      gradient toward the amniotic cavity was present only in the fetal (including
      umbilical cord and chorion) compartments. This eosinophilic gradient was present
      in 19% (90 of 465) of preterm delivery cases and was significantly more common in
      cases of PROM (54 of 193, 28%) and preterm labor (34 of 161, 21%) than abruption
      (two of 33, 6%) and preeclampsia (none of 78) (P < .001). In 84 of 90 cases
      (93%), the eosinophilic gradient was present along with multiple histologic
      indicators of acute intrauterine inflammation. CONCLUSION: An eosinophilic
      gradient toward the amniotic cavity, present in nearly a fifth of cases of
      preterm delivery, is probably of fetal origin, making it unlikely that a maternal
      "allergy-like" mechanism is a cause of preterm delivery.

PMID- 8752258
TI  - Differences between office and 24-hour ambulatory blood pressure measurement
      during pregnancy.
AB  - OBJECTIVE: To compare blood pressure (BP) measurements in ambulatory pregnant
      women with well-taken office readings. METHODS: A cohort of 209 nulliparous
      pregnant women who underwent 24-hour ambulatory BP monitoring throughout
      pregnancy was studied; 62 of these women were also studied 12 weeks after
      delivery. In addition, 30 nulligravid, nonpregnant women were studied as
      controls. RESULTS: The 24-hour median systolic and diastolic ambulatory pressures
      were higher than office pressures during pregnancy (the differences between the
      office and ambulatory systolic and diastolic BP measurements were +5 and +5.5
      mmHg at 18 weeks, +3 and +6.5 mmHg at 28 weeks, and +5 and +5.5 mmHg at 36 weeks,
      P < .001). Ambulatory BP showed a consistent rise over the three measurement
      points, resulting in higher levels of pressure at 36 weeks than those found 12
      weeks after delivery (the difference between ambulatory BP at these measurement
      points was +5 and +1 mmHg). At the postpartum measurement point, the relationship
      between ambulatory and office BP was similar to that in other surveys in
      nonpregnant women of comparable ages and in our own control group of
      nulligravidas (the difference between ambulatory and office BPs after delivery
      was +1.5 and +2 mmHg, a nonsignificant difference). CONCLUSION: There are
      important differences between ambulatory and office BPs measured throughout
      pregnancy, findings that could not be explained by activity or our present
      knowledge of cardiovascular hemodynamics in pregnancy. Ambulatory BP readings
      must be considered different entities than office BP readings. Care should be
      taken in predicting obstetric outcome from the results of ambulatory BP
      recordings.

PMID- 8752259
TI  - Development of spontaneous endometriosis in baboons.
AB  - OBJECTIVE: To determine the incidence of spontaneous endometriosis over a 32
      month period in baboons with initially normal pelves. METHODS: In this
      observational longitudinal study, which was performed at the Institute of Primate
      Research, Nairobi (Kenya), 24 baboons with laparoscopically confirmed normal
      pelves underwent 67 serial laparoscopies (mean 2.8 +/- 1.9, median 3, range 1-6)
      after 1-3 months (n = 8), 4-6 months (n = 11), 7-9 months (n = 9), 10-12 months
      (n = 17), 13-15 months (n = 6), 16-18 months (n = 4), 19-21 months (n = 3), 22-24
      months (n = 4), 25-27 months (n = 1), and 30-32 months (n = 4). During each
      laparoscopy, the pelvis was examined for the presence of endometriosis. The
      number, size, and type of endometriotic implants were noted on a pelvic map, and
      the endometriosis score and stage were tabulated according to the revised
      classification of the American Fertility Society. Taking into account the
      variable length of follow-up, we used life-table analysis to calculate the
      cumulative incidence of endometriosis. RESULTS: The cumulative incidence of
      minimal endometriosis (proven by histology) was 64% up to 32 months of follow-up.
      The eight baboons that developed proven endometriosis were followed over longer
      periods of time and had undergone more laparoscopies than the animals that did
      not develop the condition. CONCLUSION: There is a high incidence of minimal
      endometriosis in baboons, which increases with the time of follow-up and the
      number of repeat laparoscopies.

PMID- 8752260
TI  - Anterior vaginotomy: abdominal delivery without a uterine incision.
AB  - To determine whether planned anterior vaginotomy is a logical and safe means of
      avoiding a uterine scar with term abdominal delivery. I recorded the
      complications of the technique and whether vaginal birth after anterior
      vaginotomy occurred. Thirteen anterior vaginotomies were done when the vagina had
      advanced during prolonged second stage. The procedure appears safe, although one
      patient had a postpartum bladder flap hematoma and one had gross hematuria
      postpartum. Three had postpartum endometritis and one was given a blood
      transfusion. In the six with records of follow-up pregnancies, two had elective
      cesareans, four attempted vaginal birth after vaginotomy with two failures
      (delivered by cesarean). The two successful procedures were uncomplicated. I
      conclude that unintended anterior vaginotomy should be coded. Such coding and
      analysis are required before it can be recommended that anterior vaginotomy
      replace cesarean after considerable vaginal advancement occurs. Vaginal
      advancement (and cervical retraction) during the second stage of labor requires
      further study.

PMID- 8752261
TI  - Protecting the pelvic floor: obstetric management to prevent incontinence and
      pelvic organ prolapse.
AB  - OBJECTIVES: To review the literature regarding the effects of childbirth on the
      muscles, nerves, and connective tissue of the pelvic floor, review the evidence
      to support an association between childbirth and anal incontinence, urinary
      incontinence, and pelvic organ prolapse; and present recommendations for the
      prevention of these sequelae. DATA SOURCES: Sources were identified from a
      MEDLINE search of English-language articles published from 1984 to 1995.
      Additional sources were identified from references cited in relevant research
      articles. METHODS OF STUDY SELECTION: We studied articles on the following
      topics: anatomy of the pelvic floor association of childbirth with neuromuscular
      injury, biomechanical and morphologic alterations in muscle function, and
      connective tissue structure and function; the long-term effects of childbirth on
      continence and pelvic organ support; and the effects of obstetric interventions
      on the pelvic floor. TABULATION, INTEGRATION, AND RESULTS: Articles were reviewed
      and summarized. An overview of the structure and function of the pelvic floor was
      developed to provide a context for subsequent data. Childbirth was found to be
      associated with a variety of muscular and neuromuscular injuries of the pelvic
      floor that are linked to the development of anal incontinence, urinary
      incontinence, and pelvic organ prolapse. Risk factors for pelvic floor injury
      include forceps delivery, episiotomy, prolonged second-stage of labor, and
      increased fetal size. Cesarean delivery appears to be protective, especially if
      the patient does not labor before delivery. CONCLUSION: The pelvic floor plays an
      important role in continence and pelvic organ support. Obstetricians may be able
      to reduce pelvic floor injuries by minimizing forceps deliveries and
      episiotomies, by allowing passive descent in the second stage, and by selectively
      recommending elective cesarean delivery.

PMID- 8752262
TI  - The alphabet of academic medicine.
AB  - Today, academicians in obstetrics and gynecology are required to assume
      leadership roles in teaching, patient care, research, and administration. The
      junior faculty member facing these challenges needs a guide to help him or her
      adjust to the culture of the academic department. These lessons can be described
      in an alphabet of academic medicine.

PMID- 8752263
TI  - The effect of capitated and fee-for-service remuneration on physician decision
      making in gynecology.

PMID- 8752264
TI  - Ebola bar creates monkey shortage.

PMID- 8752265
TI  - Foxy logic on gene pursuit.

PMID- 8752266
TI  - Sacred cows, science and uncertainties.

PMID- 8752267
TI  - Competition for brain space.

PMID- 8752268
TI  - Synapses get smarter.

PMID- 8752269
TI  - Retrovirus restriction revealed.

PMID- 8752270
TI  - Chemokines and HIV replication.

PMID- 8752271
TI  - Transmission dynamics and epidemiology of BSE in British cattle.
AB  - A comprehensive analysis of the bovine spongiform encephalopathy (BSE) epidemic
      in cattle in Great Britain assesses past, present and future patterns in the
      incidence of infection and disease, and allows a critical appraisal of different
      culling policies for eradication of the disease.

PMID- 8752272
TI  - Two different areas within the primary motor cortex of man.
AB  - The primary motor area (M1) of mammals has long been considered to be
      structurally and functionally homogeneous. This area corresponds to Brodmann's
      cytoarchitectural area 4. A few reports showing that arm and hand are doubly
      represented in M1 of macaque monkeys and perhaps man, and that each subarea has
      separate connections from somatosensory areas, have, with a few exceptions, gone
      largely unnoticed. Here we show that area 4 in man can be subdivided into areas
      '4 anterior' (4a) and '4 posterior' (4p) on the basis of both quantitative
      cytoarchitecture and quantitative distributions of transmitter-binding sites. We
      also show by positron emission tomography that two representations of the fingers
      exist, one in area 4a and one in area 4p. Roughness discrimination activated area
      4p significantly more than a control condition of self-generated movements. We
      therefore suggest that the primary motor area is subdivided on the basis of
      anatomy, neurochemistry and function.

PMID- 8752273
TI  - Redistribution of synaptic efficacy between neocortical pyramidal neurons.
AB  - Experience-dependent potentiation and depression of synaptic strength has been
      proposed to subserve learning and memory by changing the gain of signals conveyed
      between neurons. Here we examine synaptic plasticity between individual
      neocortical layer-5 pyramidal neurons. We show that an increase in the synaptic
      response, induced by pairing action-potential activity in pre- and postsynaptic
      neurons, was only observed when synaptic input occurred at low frequencies. This
      frequency-dependent increase in synaptic responses arises because of a
      redistribution of the available synaptic efficacy and not because of an increase
      in the efficacy. Redistribution of synaptic efficacy could represent a mechanism
      to change the content, rather than the gain, of signals conveyed between neurons.

PMID- 8752274
TI  - A diffusible coupling signal from the transplanted suprachiasmatic nucleus
      controlling circadian locomotor rhythms.
AB  - The mammalian suprachiasmatic nuclei (SCN) transmit signals to the rest of the
      brain, organizing circadian rhythms throughout the body. Transplants of the SCN
      restore circadian activity rhythms to animals whose own SCN have been ablated.
      The nature of the coupling signal from the grafted SCN to the host brain is not
      known, although it has been presumed that functional recovery requires re
      establishment of appropriate synaptic connections. We have isolated SCN tissue
      from hamsters within a semipermeable polymeric capsule before transplantation,
      thereby preventing neural outgrowth but allowing diffusion of humoral signals.
      Here we show that the transplanted SCN, like neural pacemakers of Drosophila and
      silkmoths, can sustain circadian activity rhythms by means of a diffusible
      signal.

PMID- 8752275
TI  - Activation of Raf by ionizing radiation.
AB  - The critical pathways through which ionizing radiation induces malignant
      transformation and cell death are not well defined. Raf-1, a cytoplasmic serine
      threonine protein kinase, mediates the transmission of mitogenic signals
      initiated at the cell membrane to the nucleus, resulting in the activation of
      transcription factors that regulate cell growth and proliferation. Moreover, Raf
      1 overexpression and activation increases the survival response of mammalian
      cells to the toxic effects of ionizing radiation by an as-yet unknown mechanism
      (refs 3, 4 and V. Soldatenkov et al.; manuscript submitted). Somewhat analogous
      to mitogen-induced signalling, radiation stimulates protein-tyrosine kinase(s)
      and transcription factors. No direct biochemical link has been established,
      however, between radiation-stimulated protein tyrosine phosphorylation and
      downstream signals. Here we report a series of radiation-responsive events in
      which protein-tyrosine phosphorylation is followed by membrane recruitment, then
      tyrosine phosphorylation and activation of Raf-1 in vivo. Our results show that
      radiation-stimulated protein-tyrosine kinase(s) modify Raf-1, and implicate Raf-1
      in the ionizing-radiation signal-transduction pathway.

PMID- 8752276
TI  - Cooperation of the tumour suppressors IRF-1 and p53 in response to DNA damage.
AB  - Normally growing cells promptly cease DNA synthesis when exposed to genotoxic
      stresses, such as radiation, and this cell-cycle arrest prevents the accumulation
      of mutations. The transcription factor interferon regulatory factor (IRF)-1 is
      essential for the regulation of the interferon system, inhibits cell growth, and
      manifests tumour-suppressor activities. Here we show that mouse embryonic
      fibroblasts (EFs) lacking IRF-1 are deficient in their ability to undergo DNA
      damage-induced cell-cycle arrest. A similar phenotype has been observed in EFs
      lacking the tumour suppressor p53 (refs 8, 9), although the expression of IRF-1
      and p53 are independent of one another. Furthermore, we show that transcriptional
      induction of the gene encoding p21 (WAF1, CIP1), a cell-cycle inhibitor, by gamma
      irradiation is dependent on both p53 and IRF-1, and that the p21 promoter is
      activated, either directly or indirectly, by both in a transient cotransfection
      assay. These two tumour-suppressor transcription factors therefore converge
      functionally to regulate the cell cycle through the activation of a common target
      gene.

PMID- 8752277
TI  - Two distinct actions of retinoid-receptor ligands.
AB  - Signalling by all-trans retinoic acid is mediated through RXR-RAR retinoid
      receptor heterodimers, in which RXR has been considered to act as a
      transcriptionally silent partner. However, we show here that in cultured NB4
      (ref. 6) human acute promyelocytic leukaemia cells treated with either an RAR
      alpha-selective agonist alone, or certain RAR-alpha antagonists in combination
      with an RXR agonist, receptor-DNA binding is induced in vivo, resulting in
      expression of the target genes of retinoic acid as well as acute promyelocytic
      leukaemia protein (PML) relocation to nuclear bodies and differentiation before
      apoptosis. These results indicate that RAR-alpha ligands can induce two separate
      events: one enables RXR-RAR-alpha heterodimers to bind to DNA in vivo and allows
      RXR agonists to act; the other induces transcriptional activity of RAR-alpha. The
      availability of receptor-specific synthetic retinoids that can induce distinct
      receptor functions has potential in extending the therapeutic repertoire of
      retinoids.

PMID- 8752278
TI  - Dimeric ligands define a role for transcriptional activation domains in
      reinitiation.
AB  - Eukaryotic transcriptional activators mediate transcriptional induction through
      stabilization of the preinitiation complex, probably through direct interactions
      with basal transcription factors. In vitro studies on the role of an activator in
      the maintenance of on-going transcription (reinitiation) have been contradictory,
      suggesting that, after formation of a preinitiation complex, an activator may or
      may not be necessary for transcription to be maintained. We have developed a
      means of regulating transcription in living cells through the use of both
      homodimeric and heterodimerizing synthetic ligands that allow the ligand
      dependent association and disassociation of a transcriptional activation domain
      with a promoter. Here we report that maintaining the transcription of endogenous
      genes in vivo, in both yeast and human cells, requires the continuous presence of
      the activation domain. The use of synthetic ligands as a transcriptional on-off
      switch represents a powerful means of controlling the transcription in vitro and
      in vivo for both experimental and therapeutic purposes.

PMID- 8752279
TI  - Positional cloning of the mouse retrovirus restriction gene Fv1.
AB  - Vertebrate evolution has taken place against a background of constant retrovirus
      infection, and much of the mammalian genome consists of endogenous retrovirus
      like elements. Several host genes have evolved to control retrovirus replication,
      including Friend-virus-susceptibility-1, Fv1, on mouse chromosome 4 (refs 3, 4).
      The Fv1 gene acts on murine leukaemia virus at a stage after entry into the
      target cell but before integration and formation of the provirus. Although
      restriction is not absolute, Fv1 prevents or delays spontaneous or experimentally
      induced viral tumours. In vitro, Fv1 restriction leads to an apparent 50-1,000
      fold reduction in viral titre. Genetic evidence implicates a direct interaction
      between the Fv1 gene product and a component of the viral preintegration complex,
      the capsid protein CA (refs 7-9). We have now cloned Fv1: the gene appears to be
      derived from the gag region of an endogenous retrovirus unrelated to murine
      leukaemia virus, implying that the Fv1 protein and its target may share
      functional similarities despite the absence of nucleotide-sequence homology.

PMID- 8752280
TI  - The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1
      entry.
AB  - Chemokines are chemotactic cytokines that activate and direct the migration of
      leukocytes. There are two subfamilies, the CXC and the CC chemokines. We recently
      found that the CXC-chemokine stromal cell-derived factor-1 (SDF-1) is a highly
      efficacious lymphocyte chemoattractant. Chemokines act on responsive leukocyte
      subsets through G-protein-coupled seven-transmembrane receptors, which are also
      used by distinct strains of HIV-1 as cofactors for viral entry. Laboratory
      adapted and some T-cell-line-tropic (T-tropic) primary viruses use the orphan
      chemokine receptor LESTR/fusin (also known as fusin), whereas macrophage-tropic
      primary HIV-1 isolates use CCR-5 and CCR-3 (refs 7-11), which are receptors for
      known CC chemokines. Testing of potential receptors demonstrated that SDF-1
      signalled through, and hence 'adopted', the orphan receptor LESTR, which we
      therefore designate CXC-chemokine receptor-4 (CXCR-4). SDF-1 induced an increase
      in intracellular free Ca2+ and chemotaxis in CXCR-4-transfected cells. Because
      SDF-1 is a biological ligand for the HIV-1 entry cofactor LESTR, we tested
      whether it inhibited HIV-1. SDF-1 inhibited infection by T-tropic HIV-1 of HeLa
      CD4 cells, CXCR-4 transfectants, and peripheral blood mononuclear cells (PBMCs),
      but did not affect CCR-5-mediated infection by macrophage-tropic (M-tropic) and
      dual-tropic primary HIV-1.

PMID- 8752281
TI  - The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T
      cell-line-adapted HIV-1.
AB  - A putative chemokine receptor that we previously cloned and termed LESTR has
      recently been shown to function as a co-receptor (termed fusin) for lymphocyte
      tropic HIV-1 strains. Cells expressing CD4 became permissive to infection with T
      cell-line-adapted HIV-1 strains of the syncytium-inducing phenotype after
      transfection with LESTR/fusin complementary DNA. We report here the
      indentification of a human chemokine of the CXC type, stromal cell-derived factor
      1 (SDF-1), as the natural ligand for LESTR/fusin, and we propose the term CXCR-4
      for this receptor, in keeping with the new chemokine-receptor nomenclature. SDF-1
      activates Chinese hamster ovary (CHO) cells transfected with CXCR-4 cDNA as well
      as blood leukocytes and lymphocytes. In cell lines expressing CXCR-4 and CD4, and
      in blood lymphocytes, SDF-1 is a powerful inhibitor of infection by lymphocyte
      tropic HIV-1 strains, whereas the CC chemokines RANTES, MIP-1 alpha and MIP-1
      beta, which were shown previously to prevent infection with primary, monocyte
      tropic viruses, are inactive. In combination with CC chemokines, which block the
      infection with monocyte/macrophage-tropic viruses, SDF-1 could help to decrease
      virus load and prevent the emergence of the syncytium-inducing viruses which are
      characteristic of the late stages of AIDS.

PMID- 8752282
TI  - Introduction: rotavirus--from basic research to a vaccine.

PMID- 8752283
TI  - Summary of the Fifth Rotavirus Vaccine Workshop.

PMID- 8752284
TI  - The epidemiology of rotavirus diarrhea in the United States: surveillance and
      estimates of disease burden.
AB  - The decision to develop rotavirus vaccines was predicated on the extensive burden
      of rotavirus disease among children worldwide. US reports on nationwide
      hospitalizations (1979-1992) and deaths (1968-1991) due to diarrhea and weekly
      reports of rotavirus infection by 74 laboratories were reviewed to estimate the
      burden of rotavirus disease, identify epidemiologic trends, and consider methods
      for evaluating an immunization program when a vaccine becomes available. From
      1968 to 1985, diarrhea-related deaths among US children <5 years old declined
      from 1100 to 300/year. This decline was associated with the disappearance of
      winter peaks for diarrhea-related deaths previously associated with rotavirus
      infection among children 4-23 months old. From 1979 to 1992, however,
      hospitalizations for diarrhea averaged 186,000/year and retained their winter
      peaks, which have been linked to rotavirus infections. Each year an estimated
      54,000-55,000 US children are hospitalized for diarrhea, but <40 die with
      rotavirus. A rotavirus vaccine program will require improved surveillance,
      including the timely collection of data from sentinel hospitals, in which a
      diagnosis of rotavirus can be established or ruled out for all children
      hospitalized for diarrhea.

PMID- 8752285
TI  - Hospital admissions attributable to rotavirus infection in England and Wales.
AB  - Laboratory reports and data on hospital admissions were used to estimate the
      number of hospitalizations due to group A rotavirus infection in England and
      Wales. Between January 1990 and December 1994, there were 75,059 laboratory
      reports of rotavirus infection, and 66,062 of these were in children <5 years
      old; rotavirus represented 39% of all pathogens identified in fecal specimens
      from this age group. Between April 1993 and March 1994, 1904 hospital admissions
      coded as "infectious intestinal disease" and 2354 coded as "noninfective
      gastroenteritis" occurred in children <5 in the North Thames region (a health
      authority representing 13% of the population in England and Wales). By modeling
      admission and laboratory reporting data, it was estimated that 54% of
      hospitalizations for intestinal infectious disease and 34% for noninfective
      gastroenteritis were attributable to rotavirus. By extrapolation of the North
      Thames data, it was estimated that 17,810 rotavirus-related hospitalizations
      (5/1000 children <5 years old) occurred in England and Wales during the same
      period. Effective vaccines have the potential to substantially reduce the number
      of hospital admissions due to group A rotavirus infection.

PMID- 8752286
TI  - The impact of rotavirus disease in Venezuela.
AB  - Information concerning the disease burden of rotavirus, particularly in
      developing countries, has important implications for the use and for monitoring
      the impact of rotavirus vaccines. Although rotavirus has been recognized as the
      most frequent cause of hospitalization in the world, national estimates and
      specific information about the incidence of hospitalization for rotavirus
      gastroenteritis are very limited. Consequently, estimates of the incidence of
      hospitalization among children during the first 2 years of life in Venezuela were
      determined by extrapolation of data from a community-based study carried out in
      Caracas.

PMID- 8752287
TI  - Serum, fecal, and breast milk rotavirus antibodies as indices of infection in
      mother-infant pairs.
AB  - Sixty-eight mother-infant pairs were followed for 12-17 months after birth.
      Rotavirus infections in children were detected by EIA of weekly fecal antigen and
      anti-rotavirus IgA levels, by EIA of anti-rotavirus IgG in sera at birth, 6, or
      12-17 months of age, and by anti-rotavirus EIA IgA and neutralizing antibody (NA)
      in monthly samples of maternal breast milk. Primary rotavirus infection was
      detected in 26 children (in 15 [58%] by fecal excretion, 12 [46%] by IgG
      seroconversion, and 22 [85%] by elevations of IgA anti-rotavirus antibodies [IgA
      coproconversion] in consecutive fecal specimens). Rotavirus "challenge" was
      detected by rises in levels of NA in breast milk in 9 (47%) of 19 mothers,
      including 5 (26%) from pairs in which there was no other evidence of rotavirus
      infection. Reinfections were detected in 2 children by rotavirus excretion and in
      4 by coproconversion. IgA coproconversion is the most sensitive technique for
      detection of symptomatic and asymptomatic rotavirus infection in young children.

PMID- 8752288
TI  - Review of G and P typing results from a global collection of rotavirus strains:
      implications for vaccine development.
AB  - Candidate rotavirus vaccines have been prepared with reassortant strains
      specifically to protect against the 4 major rotavirus G serotypes (G1 -4). Many
      studies using P (VP4) genotyping methods have indicated that, worldwide,
      rotavirus strains of the 4 common G serotypes are each associated with 1 P
      genotype: GI, G3, and G4 are associated with P[8], and G2 is associated with
      P[4]. In contrast, G and P genotyping of rotavirus in specimens from India
      revealed that a high percentage of the childhood diarrhea strains belong to
      genotype P[6], and the most common strain had an unusual G serotype, G9.
      Similarly, in all regions surveyed in Brazil, apparent reassortants of genotype
      P[8], G5 were found in children with gastroenteritis. These studies indicate that
      while rotavirus strains have limited diversity in many settings, reassortment
      between common and uncommon serotypes or animal strains can arise in some
      settings and, thus, lead to unusual diversity.

PMID- 8752289
TI  - Advances in molecular biology: impact on rotavirus vaccine development.
AB  - The first candidate rotavirus vaccine was a live attenuated oral vaccine made by
      the classical empirical method of serial passage of virus in tissue culture
      cells. Current tetravalent vaccine candidates that are in the final stages of
      efficacy testing in the United States were made by genetic reassortment. This
      article briefly highlights how advances in the basic understanding of the
      molecular biology of rotaviruses have facilitated vaccine development. New
      approaches for second-generation vaccines and improvements in vaccine efficacy
      based on further exploitation of the tools and knowledge of rotavirus molecular
      biology and pathogenesis are discussed.

PMID- 8752290
TI  - Molecular determinants of immunity and pathogenicity of rotavirus infection in
      the mouse model.
AB  - Rotavirus-induced diarrhea is responsible for the death of approximately 800,000
      children per year. Jennerian and modified Jennerian anti-rotavirus vaccines
      currently being tested have a moderate protective effect against rotavirus
      disease. Optimization of these vaccines, development of more efficient rationally
      designed vaccines, and identification of other strategies to prevent or treat
      rotavirus disease will rely on a thorough understanding of the host-virus
      relationship and especially on the immune mechanisms developed by the host
      against rotavirus. Recent advances in our understanding of the mouse model of
      rotavirus infection will enhance the understanding of human rotavirus disease.

PMID- 8752291
TI  - Mechanisms of protection against rotavirus in humans and mice.
AB  - Immune responses following either natural or experimental rotavirus infection
      provide protection against subsequent rotavirus illnesses, and the mechanisms
      involved have been examined in humans and animals. In adult volunteers challenged
      with human rotaviruses, protection has been shown to correlate with serum and
      intestinal antibodies; however, titers of no specific antibody could be used
      reliably as a marker of protection, including neutralizing antibody to the
      challenge virus. Studies in children confirmed these general associations between
      antibody titers and protection, but the serotype specificity of antibody and its
      role in protection remained unclear. Studies in mice suggested antibody, CD8
      cells, and a third, undetermined, factor as mediators of protection. Antibody
      appeared to be most important, both in resolution of infection and protection
      against subsequent infection, but its activity was not serotype specific. CD8
      cells helped resolve rotavirus infection but were less important in protection
      against reinfection. The third factor remains to be identified.

PMID- 8752292
TI  - Host factors associated with protection against rotavirus disease: the skies are
      clearing.
AB  - Over the past several years, a number of studies have clarified aspects of
      rotavirus immunology and vaccinology previously considered controversial. In this
      review, studies that address the following questions will be summarized: Which
      host factors are responsible for recovery from acute rotavirus infection? Are the
      host factors responsible for recovery from acute infection the same as those
      necessary for prevention of infection? What is the relative importance of the
      nature of the inoculum (e.g., homologous or heterologous host virus and live or
      inactivated virus), route of inoculation, or virus serotype in vaccine
      development? What is the immunologic basis by which infection with 1 viral
      serotype protects against challenge with another serotype (heterotypic
      protection)?

PMID- 8752293
TI  - Efficacy of a quadrivalent rhesus rotavirus-based human rotavirus vaccine aimed
      at preventing severe rotavirus diarrhea in infants and young children.
AB  - The most extensively explored strategy for rotavirus vaccination has been the
      Jennerian approach, which uses an antigenically related rotavirus strain from an
      animal host as the immunogen to induce protection against the 4 epidemiologically
      important group A rotavirus VP7 serotypes. Because this approach has shown
      limited efficacy, a modified Jennerian approach was developed with the goal of
      achieving broader antigenic coverage. Four VP7 serotypes were incorporated into a
      quadrivalent vaccine comprised of three rhesus-human rotavirus reassortants, each
      with 10 rhesus rotavirus genes and 1 human rotavirus gene that encodes VP7
      serotype 1, 2, or 4 specificity; the rhesus rotavirus itself provides coverage
      for VP7 serotype 3. This approach appears quite promising for preventing severe
      rotavirus diarrhea, including those episodes that lead to dehydration. Additional
      strategies under development stress the role not only of human rotavirus VP7 but
      also of human rotavirus VP4, the other outer capsid protein that also induces
      neutralizing antibodies.

PMID- 8752294
TI  - The development of multivalent bovine rotavirus (strain WC3) reassortant vaccine
      for infants.
AB  - Laboratory and clinical studies have been directed toward development of a
      vaccine against rotavirus gastroenteritis in infants. First, bovine rotavirus
      strain WC3, which did not induce neutralizing antibodies to predominant human
      rotavirus (HRV) serotypes, was determined to be safe and immunogenic; however, it
      was not protective in all efficacy trials. HRVs adapted to cell culture retained
      some virulence for infants, but when further attenuated by cold adaptation, they
      were poorly immunogenic. Reassortant rotaviruses were designed to express HRV
      surface proteins VP7 (G) or VP4 (P) while retaining a bovine WC3 genome
      background. Reassortants containing either HRV surface protein and as few as four
      bovine rotavirus genes were safe in infants. A monovalent WC3 reassortant of
      serotype G1 specificity was 64%-100% protective in placebo-controlled trials. A
      quadrivalent WC3 reassortant vaccine with components of HRV G1, G2, G3, and P[8]
      specificity induced 67% protection against all rotavirus disease in a multicenter
      efficacy trial.

PMID- 8752295
TI  - Review of rotavirus vaccine trials in Finland.
AB  - Oral rotavirus vaccines, including bovine rotavirus strains RIT 4237 and RIT
      4256, rhesus rotavirus (RRV) vaccine, rhesus-human rotavirus vaccine reassortants
      (D x RRV, DS-1 x RRV, and tetravalent RRV), and human nursery rotavirus strain
      M37, have been evaluated in 5353 Finnish infants for safety, immunogenicity, and
      efficacy against rotavirus gastroenteritis. Bovine rotavirus vaccines were
      nonreactogenic in infants, whereas RRV-based and M37 vaccines were occasionally
      associated with febrile reactions 2-5 days after vaccination. All vaccines showed
      dose-dependent immunogenicity. Vaccine efficacy correlated with overall
      immunogenicity but not with the vaccine virus G serotype. For each vaccine,
      protective efficacy was better against severe rotavirus disease than against any
      rotavirus-associated gastroenteritis. Maximal protective efficacy against any
      rotavirus gastroenteritis in subjects with demonstrable vaccine immunogenicity
      was approximately 75%. To achieve similar protection in all vaccinees, efforts
      should be focused on enhancing the immunogenicity of oral rotavirus vaccines.

PMID- 8752296
TI  - Virus-like particles as a rotavirus subunit vaccine.
AB  - Rotavirus subunit vaccines are being evaluated for use in humans. The virus-like
      particles (VLPs) for these vaccines are produced in insect cells coinfected with
      combinations of baculovirus recombinants expressing bovine RIF VP2 and simian
      SA11, VP4, VP6, or VP7 rotavirus proteins. VLPs were administered parenterally to
      mice and rabbits, and the immunogenicity and protective efficacy of the vaccines
      were evaluated. Rabbits vaccinated with VP2/4/6/7 or VP2/6/7 VLP combinations
      developed high levels of rotavirus-specific serum antibody and fecal IgG but not
      fecal IgA. The induction of fecal IgG was associated with total or partial
      protection from oral challenge with ALA rotavirus. Heterotypic serum and fecal
      neutralizing antibody was induced in mice vaccinated parenterally with G1 VP2/6/7
      or VP2/4/6n VLPs. VLPs were highly immunogenic when administered in QS21
      adjuvant, inducing serum neutralizing antibody titers comparable to those induced
      by SA11 virus. VLPs are effective immunogens when administered parenterally and
      may be an effective subunit vaccine.

PMID- 8752297
TI  - Protection against rotavirus infections by DNA vaccination.
AB  - DNA vaccines encoding for murine rotavirus proteins VP4, VP6, or VP7 were tested
      in adult BALB/c mice for their ability to induce immune responses and protect
      against rotavirus challenge. A gene gun was used to inoculate vaccines into the
      epidermis. Rotavirus-specific serum antibodies, as measured by ELISA, and virus
      specific cytotoxic T lymphocyte responses were generated by each of the three
      vaccines, but virus-neutralizing antibodies were detected only in mice that were
      inoculated with DNA vaccines encoding for VP4 and VP7. Efficacy of the vaccines
      was determined by challenge with 100 ID50 of homotypic rotavirus. Each of the
      three vaccines was effective in protecting mice against infection after rotavirus
      challenge as determined by reduction (P < .001) in virus excretion in mice
      receiving the DNA vaccines. These results demonstrate that DNA vaccination has
      potential as a new approach for control of rotavirus infections.

PMID- 8752298
TI  - Group A rotavirus veterinary vaccines.
AB  - Group A rotaviruses cause diarrhea in young livestock and poultry; consequently,
      vaccination strategies have focused on induction of active or passive immunity.
      Gnotobiotic pigs and calves serve as useful models to evaluate induction of
      active immunity by candidate animal or human rotavirus vaccines. However, live
      attenuated rotavirus vaccines lacked efficacy when administered orally to calves
      and pigs in the field, presumably because colostral antibodies inhibited vaccine
      virus replication. The widespread occurrence of rotavirus antibodies in colostrum
      led to strategies for maternal rotavirus vaccination to boost lactogenic immunity
      and transfer passive antibodies to the neonate via colostrum and milk. The
      variable success of maternal rotavirus vaccines in the field is influenced by
      vaccine dose, strain, inactivating agent, adjuvant, route of administration, and
      environmental rotavirus exposure levels. The use of genetically engineered
      rotavirus-like particle vaccines in cows to boost antibodies in mammary
      secretions shows promise. Such subunit vaccines possess potential advantages over
      existing vaccines.

PMID- 8752299
TI  - Influence of breast-feeding and oral poliovirus vaccine on the immunogenicity and
      efficacy of rotavirus vaccines.
AB  - To be practical and cost effective, rotavirus vaccines will have to be
      administered to infants with routine childhood vaccinations. Rotavirus vaccine
      studies were reviewed to evaluate the effect of breast-feeding and concurrent
      oral poliovirus vaccination (OPV) on the immunogenicity and efficacy of oral
      rotavirus vaccines. Both breast-feeding and OPV appeared to interfere, to some
      degree, with the serum immune response to rotavirus vaccines; however, the
      effects were usually not statistically significant and were largely overcome by
      administering three doses of rotavirus vaccine rather than one. Available data
      show no decrease in the protective efficacy of rotavirus vaccine in breast-fed
      children or in children receiving concurrent OPV, but larger sample sizes will be
      required to definitely rule out any effect.

PMID- 8752300
TI  - Selected regulatory and scientific topics for candidate rotavirus vaccine
      development.
AB  - Various aspects of the development of rotavirus vaccine candidates are discussed.
      As is true with other vaccines, comprehensive testing must be done to detect the
      possible presence of adventitious agents in the vaccine and seed preparations.
      Consideration must also be given to other biologic materials that come in contact
      with the vaccine preparation during production to prevent the introduction of
      contaminants. The clinical testing of rotavirus vaccines from early safety and
      immunogenicity studies through final efficacy studies is also discussed. Issues
      surrounding coadministration of investigational rotavirus vaccines with US
      licensed vaccines are ideally addressed before initiation of efficacy trials.
      Other subjects discussed are identification of correlates of protection,
      multivalent vaccines, foreign efficacy trials, safety data, and statistical
      considerations. Sponsors of investigational vaccines are urged to contact the
      Food and Drug Administration for guidance during the development process,
      especially before the investigational new drug application and pivotal efficacy
      trial stages.

PMID- 8752301
TI  - Rotavirus vaccines--from licensure to disease reduction.
AB  - Rotavirus infection produces a serious health burden in the United States,
      causing an estimated > 100,000 hospitalizations and > 100 deaths annually. This
      health burden is comparable to that for measles, pertussis, mumps, and varicella
      before vaccines for these diseases were routinely given to children. Rotavirus
      vaccines have the potential to significantly reduce a serious public health
      problem in the United States. However, while development and licensure of
      vaccines is a major breakthrough, it represents only the first step in disease
      prevention. Vaccines must be recommended by major immunization advisory
      committees, financed in both the public and private sectors, and successfully
      integrated into the existing vaccination schedule. Vaccines must reach all
      targeted children, and monitoring systems must be established or adapted to
      better determine vaccine safety and disease impact. Reevaluation of disease
      prevention strategies must be ongoing and fueled by new information on safety and
      disease reduction.

PMID- 8752302
TI  - Genomic instability induced by ionizing radiation.
AB  - Genomic instability is characterized by the increased rate of acquisition of
      alterations in the mammalian genome. These changes encompass a diverse set of
      biological end points including karyotypic abnormalities, gene mutation and
      amplification, cellular transformation, clonal heterogeneity and delayed
      reproductive cell death. The loss of stability of the genome is becoming accepted
      as one of the most important aspects of carcinogenesis, and the numerous genetic
      changes associated with the cancer cell implicate genomic stability as
      contributing to the neoplastic phenotype. Multiple metabolic pathways govern the
      accurate duplication and distribution of DNA to progeny cells; other pathways
      maintain the integrity of the information encoded by DNA and regulate the
      expression of genes during growth and development. For each of these functions,
      there is a normal baseline frequency at which errors occur, leading to
      spontaneous mutations and other genomic anomalies. This review summarizes the
      current status of knowledge about radiation-induced genomic instability. Those
      events and processes likely to be involved in the initiation and perpetuation of
      the unstable phenotype, the potential role of epigenetic factors in influencing
      the onset of genomic instability, and the delayed effects of cellular exposure to
      ionizing radiation are discussed.

PMID- 8752303
TI  - Gamma-ray-induced cell killing and chromosome abnormalities in the bone marrow of
      p53-deficient mice.
AB  - Resistance to the lethal effects of ionizing radiation has been demonstrated in a
      wide variety of cell types with defects in the p53 gene (thymocytes, splenic B
      and T cells, in vitro hemopoietic colony-forming cells and intestinal cells of
      the mouse, embryo cells of the rat, and human Burkitt's lymphoma cells). In
      contrast, Slichenmeyer et al. (Cancer Res. 53, 4164-4167, 1993) found no evidence
      of resistance in fibroblasts derived from p53 null mice. The aim of our study was
      to compare the radiation response of hemopoietic colony-forming cells (in vitro
      CFC) and of fibroblastoid colony-forming cells or units (CFU-F) within the same
      tissue (marrow) in p53 null mice (-/-), heterozygotes (+/-) and wild-type animals
      (+/+). We have also tested the hypothesis that, in proliferating cells, radiation
      induced cell killing is mediated through chromosome damage by examining the
      relationship between these end points in hemopoietic cells of the three mouse
      types. Both in vitro CFC and CFU-F of -/- mice were resistant to cell killing
      compared with +/+ and +/- mice whose cellular sensitivities were
      indistinguishable. The resistance was characterized by a broader "shoulder" on
      the cell survival curve, i.e. a higher extrapolation number but similar D0 values
      using the multitarget model or a lower alpha coefficient using the linear
      quadratic model. The frequency of chromosomally abnormal marrow cells after
      irradiation was similar for the three genotypes. However, marrow cells with
      aberrations carried more aberrations in -/- mice than in +/+ or +/- mice such
      that the total number of aberrations per 100 cells was higher in -/- mice. Since
      there were no differences in the yields of aberrations between genotypes in
      spleen lymphocytes or in CFU-F (both noncycling at the time of irradiation) and
      less mitotic inhibition in -/- marrow cells than in +/+ or +/- cells, the
      chromosomal radiosensitivity of -/- marrow hemopoietic cells might be related to
      reduced cell cycle delay allowing insufficient time for repair, but other
      explanations have been considered. We postulate that the radiation resistance of
      both hemopoietic CFC and CFU-F in -/- mice is a consequence of the failure of
      DNA/chromosome damage to trigger apoptosis or permanent cell cycle arrest to the
      same extent as in the +/+ or +/- mice: hence the lack of correlation between
      chromosome damage and cell death in the three mouse types.

PMID- 8752304
TI  - Radiation inactivation of human prostate cancer cells: the role of apoptosis.
AB  - Radiation-induced apoptosis detected by gel electrophoresis was measured in cells
      of three human prostate carcinoma cell lines (TSU, PC-3 and DU-145) and compared
      to their intrinsic radiosensitivities as measured by clonogenic assays. The
      intrinsic radiosensitivities of each cell line were defined by their alpha and
      beta coefficients and their surviving fraction at 2 Gy, derived from complete
      survival curves. The temporal expression and kinetics of radiation-induced
      apoptosis for DU-145 cells, the human prostate carcinoma cell line which
      expressed the highest rate of radiation-induced apoptosis, was characterized
      further by differential sedimentation and the immunofluorescence assay (Apoptag)
      which was specific for 3'-OH ends in cellular DNA. Cell viability was measured
      microscopically with trypan blue staining. Cell survival after various doses was
      computer-fitted to either a simple linear or a linear-quadratic equation. Twenty
      four hours after a 10-Gy dose of 137Cs gamma rays, DNA fragmentation to
      nucleosome multimers was strongly expressed in only DU-145 cells. In this cell
      line, when centrifugation at 12,000g for 10 min was used to separate fragmented
      from large molecular weight DNA, the proportion of DNA in the supernatant
      increased to a maximum of approximately 17% of the total by 10-12 h after
      radiation treatment. Cell death 24 h after irradiation measured by trypan blue
      exclusion assays followed single-hit kinetics up to 80 Gy. The proportion of
      cells which were labeled with Apoptag displayed single-hit kinetics and yielded
      the same inactivation coefficient as measured by trypan blue. Together, these
      data indicate that the rapid (24 h) inactivation of irradiated DU-145 cells
      results from apoptosis and accounts for about 5% of the single-hit killing
      measured by clonogenic assay. Temporal studies of radiation-induced killing of DU
      145 cells distinguished this rapid mechanism of cell death from the major
      mechanism (72-144 h). These may correlate with apoptosis and proliferative cell
      death, respectively. Of the three prostate cancer cell lines investigated, only
      DU-145 cells displayed significant levels of radiation-induced DNA fragmentation
      and rapid cell death, with characteristics of apoptosis. This mechanism of cell
      death was complete by 24 h after irradiation and was well separated in time from
      the death of cells by the major mechanisms which occurred after 72 h, and
      accounted for about 5% of cell inactivation by a single-hit mechanism.

PMID- 8752305
TI  - Apoptosis and delayed expression of c-jun and c-fos after gamma irradiation of
      Jurkat T cells.
AB  - The purpose of this study was to determine the role of radiation-induced
      expression of c-jun and c-fos in radiation-induced apoptosis of cells of the
      Jurkat T-cell line. Doses of 10-20 Gy caused a massive number of cells to undergo
      apoptosis within the first 24 h. This was accompanied by extensive increases in c
      jun mRNA levels and moderate increases in c-fos levels, both occurring at the
      time of onset of internucleosomal DNA fragmentation. Increased c-jun and c-fos
      expression was maximum at 8 h after irradiation with a 10-fold increase in c-jun
      and a 2-fold increase in c-fos mRNA levels. In comparison, stimulation of the
      Jurkat cells with PMA resulted in rapid induction of c-jun and c-fos within 1 h.
      The late induction of c-jun and c-fos was not preceded by induction of tumor
      necrosis factor-alpha (TNF-alpha) or the bifunctional repair endonuclease and
      nuclear redox factor Ref-1; rather a slow decrease in Ref-1 mRNA levels was found
      over the first 24 h. Our results showed that radiation-induced c-jun and c-fos
      expression is a late response in Jurkat cells, and is most likely a secondary
      effect not necessary for radiation-induced apoptosis. Furthermore, apoptosis was
      induced by the RNA synthesis inhibitor actinomycin D, which does not induce c-jun
      or c-fos expression. This demonstrates that massive late induction of c-jun and c
      fos is not a general requirement for apoptosis in Jurkat cells.

PMID- 8752306
TI  - Heat-induced changes in intracellular sodium and membrane potential: lack of a
      role in cell killing and thermotolerance.
AB  - Hyperthermia induces transient changes in intracellular free sodium levels and
      membrane potential. The possible role of these changes in cell killing by
      hyperthermia and thermotolerance has been evaluated using Chinese hamster ovary
      IS1 and HeLa cells. Intracellular sodium was measured with Sodium Green and SBFI,
      while membrane potential was measured with the oxonol dye diBAC4(3). Heating at
      either 42.0 or 45.0 degrees C caused nearly the same decrease in free [Na+]i from
      about 20 mM in unheated cells to 5-7 mM in heated cells. However, survival
      differed by over two orders of magnitude after heating for 30 min at these two
      temperatures. In addition, blockage of the heat-induced decrease in [Na+]i using
      ouabain and/or amiloride did not affect the survival curves for heated cells.
      Hyperthermia also induced a membrane hyperpolarization of 15 mV after 15 min at
      42.0 degrees C or 35 mV after 15 min at 45.0 degrees C which could be blocked
      with ouabain and amiloride. Both the free [Na+]i and membrane potential recovered
      to near baseline levels within 30-40 min after heating. Induction of
      thermotolerance using a 45.0 degrees C, 10-min heat treatment also was not
      affected by ouabain and/or amiloride. Finally, thermotolerant cells experienced
      the same heat-induced changes in free [Na+]i and membrane potential as non
      thermotolerant cells. We conclude that the heat-induced changes in free [Na+]i
      and membrane potential are not directly related to cell killing by hyperthermia
      or thermotolerance.

PMID- 8752307
TI  - Sequencing of combined hyperthermia and photodynamic therapy.
AB  - Photodynamic therapy (PDT) and hyperthermia are two alternative tumor treatment
      modalities currently being investigated in clinical trials. It has been suggested
      that, due to the differences in cell-killing mechanisms, synergetic tumor
      responses may be achieved if the two modalities are combined in appropriate
      sequences. This hypothesis is tested in the current study by delivering graded
      PDT doses during a transient tumor reoxygenation period after a hyperthermia
      treatment, or delivering graded hyperthermia doses when the tumor becomes acidic
      and hypoxic after a PDT treatment. The results indicate that the latter
      combination sequence has a profound effect on tumor response. While treating the
      tumors with PDT followed by hyperthermia evokes a synergetic tumor response,
      reversing the sequence results only in an additive effect. Possible mechanisms
      associated with tissue oxygenation are discussed.

PMID- 8752308
TI  - Binding of radioprotective thiols and disulfides in Chinese hamster V79 cell
      nuclei.
AB  - Binding of thiols of varying charge (Z) in nuclei prepared in suspension was
      determined to assess the extent to which histones, Mg2+ spermine and chromatin
      structure influence counter-ion condensation of cationic thiols and co-ion
      depletion of anionic thiols at DNA. The nuclei were prepared in suspension
      buffer, washed and incubated in buffer containing thiol and graded amounts of
      Mg2+ and spermine. The nuclei were separated from the incubation medium by
      centrifugation through silicone oil, and the thiols were determined in the
      nuclear pellet and in the incubation buffer by labeling with monobromobimane and
      HPLC. Measurements of the water content of nuclei indicated that chromatin was
      fully condensed in buffer containing 5 mM MgCl2 and 115 mM KCl. Under these
      conditions nuclei incubated in 1 mM substrate had concentrations of 0.80 +/- 0.21
      mM glutathione (Z = -1), 1.05 +/- 0.12 mM 2-mercaptoethanol (Z = 0), 0.95 +/-
      0.15 mM cysteine (Z = 0), 0.75 +/- 0.29 mM cysteamine (Z = +1), 2.5 +/- 0.3 mM WR
      1065 (Z = +2), 3.4 +/- 0.5 mM WR-35980 (Z = +3) and 12 +/- 2 mM WR-33278
      (disulfide of WR-1065, Z = +4), respectively. Spermine up to 1 mM in the presence
      of 5 mM Mg2+ had little effect upon the binding of these thiols and disulfide,
      but did suppress the binding of 0.1 mM WR-33278, the results indicating that WR
      33278 and spermine compete for the same sites with comparable affinity. From the
      results observed and the assumption that deviations from the bulk solution
      concentration (1 mM) result from counter-ion condensation within 3 nm of DNA, we
      estimate that WR-1065 (Z = +2), WR-35980 (Z = +3) and WR-33278 (Z = +4) were
      concentrated near DNA 6-, 8- and 20-fold, respectively, in the presence of
      histones, 5 mM Mg2+ and 1.0 mM spermine.

PMID- 8752309
TI  - The effect of the mass and initial chemical form of neptunium on its molecular
      associations in blood and liver.
AB  - The present investigation was aimed at establishing the distribution of neptunium
      in blood and liver cells as a function of the mass and chemical form of the
      radionuclide injected. Four groups of rats received intravenous injections of
      237Np(V), 237Np(IV), 239Np(V) or 239Np(IV). Twenty-four hours after injection of
      the radionuclide, subcellular structures of the liver were separated by
      ultracentrifugation and serum and liver cytosol were subjected to gel permeation
      chromatography. The intracellular distribution of neptunium in liver depends on
      the mass of the radionuclide injected; the relative specific activity for 237Np
      compared to 239Np was 2 in nuclei and 0.5-0.9 in cytosol. By contrast, the
      initial chemical form of the radionuclide has no significant effect on its
      intracellular distribution. In cytosol, neptunium was bound mainly by two
      proteins of molecular weight 450 and 200 kDa, respectively. The former was
      identified as ferritin, but the latter remains unidentified. In this compartment,
      no effect of mass or chemical form was seen. In blood, the bulk of the
      radionuclide was bound to transferrin whatever the mass and initial chemical form
      injected.

PMID- 8752310
TI  - Boron neutron capture irradiation of the rat spinal cord: histopathological
      evidence of a vascular-mediated pathogenesis.
AB  - A histopathological study was carried out on the spinal cord of rats after boron
      neutron capture (BNC) irradiation. Rats were irradiated with thermal neutrons
      alone or in combination with borocaptate sodium (BSH) or p-boronophenylalanine
      (BPA). Spinal cords were examined 1 year after irradiation, or at earlier times
      in rats developing myelopathy. Considered overall, the pathology of the spinal
      cord after BNC irradiation was comparable with that reported previously after X
      irradiation of the spinal cord in the identical strain of rat. When BSH was used
      as the neutron capture agent, the biologically effective dose of radiation
      delivered to the CNS parenchyma was a factor of -2.7 lower than that delivered to
      the vascular endothelium. In effect, the blood vessels were selectively
      irradiated using this BNC modality. The resultant pathology was similar to that
      observed after irradiation with thermal neutrons alone or in the presence of BPA,
      situations in which the CNS vasculature was not selectively irradiated. This
      points to the vascular endothelium as being the critical target cell population,
      damage to which results in the development of the lesions seen in the spinal cord
      after BNC irradiation and, by inference, after irradiation with more conventional
      modalities.

PMID- 8752311
TI  - Dose-response effects of radiation on the permeability of endothelial cells in
      culture.
AB  - Increased permeability is an early and universal response of the vasculature to
      radiation injury, yet the biological basis of this reaction is poorly understood.
      The present study determined the time course and the dose-response relationship
      of radiation-induced hyperpermeability in cultured bovine pulmonary artery
      endothelial (BPAE) cells. BPAE cells were grown to a confluent monolayer on
      microcarrier beads, and column chromatography methods were used to evaluate
      permeability to two low molecular weight compounds: sodium fluorescein (NaFlsc,
      mol. wt. = 342) and cyanocobalamin (B12, mol. wt. = 1355). This is a novel in
      vitro model to study mechanisms and modifiers of radiation-induced permeability
      of endothelial cells under flow conditions using nonradioactive tracers. Cell
      covered beads were exposed to a single dose of 10 Gy Of 137Cs gamma rays and
      placed in the column, and permeability was measured every 30 min for 3 h. There
      was a time-dependent increase in permeability to both tracers, reaching
      significance by 2 h. Increased permeability was accompanied by perturbations in F
      actin distribution in the BPAE cells as determined by rhodamine-phalloidin
      fluorescence microscopy. Neither catalase nor captopril ameliorated this
      hyperpermeability, but dibutyryl cAMP partially prevented it. At 3 h after 0, 1,
      2, 5 and 10 Gy irradiation, permeability values of 11.8 +/- 2.1, 13.9 +/- 2.2,
      20.9 +/- 3.6, 24.8 +/- 2.8 and 27.2 +/- 3.3 (10(-5) cm/s, +/- SEM), respectively,
      were observed using NaFlsc. The increase was significant (P < 0.05) at 2 Gy or
      higher. Permeability to B12 was significantly elevated after 5 or 10 Gy. These
      results suggest that permeability of endothelial cells to low molecular weight
      solutes increases within 3 h after therapeutic doses of radiation, and that cAMP
      ameliorates this response.

PMID- 8752312
TI  - The effect of low-dose irradiation on proliferation of mammalian cells in vitro.
AB  - The effect of low doses of gamma radiation on proliferation of Raji lymphoma
      cells and Chinese hamster fibroblasts in vitro has been investigated. It is shown
      that irradiation in the dose range between 2 and 20 cGy (maximum at 10 cGy)
      stimulates growth of cultured cells due to the shortening of the lag phase of
      cell growth, with the duration of the doubling time being unchanged.
      Preirradiation of growth medium in this dose range also stimulates cell
      proliferation, though to a lesser extent than irradiation of cells and the medium
      does. The stimulatory effect manifests itself in an increase in the cell number
      as well as in the size and number of colonies.

PMID- 8752313
TI  - Sonochemical formation of gold particles in aqueous solution.
AB  - Gold(III) ions in aqueous solutions of NaAuCl4 were reduced to form gold
      particles by ultrasonic irradiation. The rate of formation of gold particles was
      accelerated in the presence of certain organic additives such as surfactants,
      water-soluble polymers and aliphatic alcohols and ketones. The rates of formation
      of gold particles from 1 mM Au(III) ions in pure water were 3 microM min-1 under
      argon atmosphere and approximately zero under air, and in solutions containing
      additive the rates were 9-133 microM min-1 under argon and 8-40 microM min-1
      under air. Surfactants stabilized the particles as colloidal state for more than
      several months. The rates of formation of both hydrogen atoms and hydroxyl
      radicals were estimated to be equal to 25 microM min-1 in the sonolysis of pure
      water under argon. Three reaction pathways leading to the reduction of metal ions
      were proposed: (1) reduction by hydrogen atoms; (2) reduction by reducing
      radicals formed via reactions of hydroxyl radicals or hydrogen atoms with the
      additives; (3) reduction by radicals formed from thermal reaction of the
      additives at the interfacial region between cavitation bubbles and bulk solution
      and/or in the cavities. The order of the contribution of these three pathways to
      the reduction of gold ions was (3) > (2) > (1) in most cases. The number averages
      of the size of gold particles formed in surfactant solutions under argon
      atmosphere were about 10 nm with a fairly narrow size distribution.

PMID- 8752314
TI  - Cataract in atomic bomb survivors based on a threshold model and the occurrence
      of severe epilation.
AB  - This report re-examines the relationship of radiation dose to the occurrence of
      cataracts among 1742 atomic bomb survivors seen in the years 1963-1964 for whom
      the degree of epilation and Dosimetry System 1986 (DS86) doses are known. Of
      these individuals, 67 had cataracts. A relative risk model with two thresholds,
      one for the epilation group and the other for the no-epilation group, has been
      fitted to the data using a binomial odds regression approach and a constant
      relative biological effectiveness (RBE) for neutrons of 10. Among these models, a
      linear-linear (L-L) dose-response relationship with two thresholds presents the
      best fit. Under the L-L threshold model based on DS86 eye organ dose estimates
      for the epilation and no-epilation groups, the slope estimate for the epilation
      group was 1.6-2.0 times greater than that for the no-epilation group, but no
      statistical difference between the two slope estimates was noted. The estimated
      threshold for the epilation group was 0.86 Sv and 1.54 Sv for the no-epilation
      group, but again the difference between the two threshold estimates is not
      statistically significant. When an L-L relative risk model with two thresholds
      was fitted to the data assuming the dose estimates to be in error by 35%, or when
      the data were restricted to the 1105 individuals exposed in Japanese houses at
      distances of less than 2500 m, where the DS86 doses are thought to be most
      reliable, the results were almost the same as those for the individuals for whom
      unadjusted DS86 eye organ dose estimates were used.

PMID- 8752315
TI  - Chromosomal abnormalities in neutron-induced acute myeloid leukemias in CBA/H
      mice.
AB  - Acute myeloid leukemias (AMLs) induced in CBA/H mice by 1 MeV fission neutrons
      have been examined for chromosomal abnormalities by G-band analysis. In common
      with X-ray- and alpha-particle-induced AMLs in CBA/H mice, more than 90% (16/17)
      of the myeloid leukemias had chromosome 2 abnormalities, in this case, all
      interstitial deletions. Chromosome 2 breakpoints were not wholly consistent, but
      clustering in three specific G-band regions was observed. Very distal (H-region)
      breakpoints were more common in the neutron AMLs than in X-ray- or alpha-particle
      induced leukemias. These data indicate that neutron-induced AMLs in CBA/H mice
      are not characterized by a specific chromosome deletion but that a variety of
      chromosome 2 deletion types are associated with the disease. Trisomy of
      chromosome 1(12.5% AMLs) and aneusomy of chromosomes 6 (31% AMLs) and Y (37.5%
      AMLs) were noted. While chromatid breakage was observed occasionally in neutron
      induced AML, no clear indications of persistent chromosomal instability or high
      levels of stable chromosomal change were apparent.

PMID- 8752316
TI  - Strain-dependent susceptibility to radiation-induced mammary cancer is a result
      of differences in epithelial cell sensitivity to transformation.
AB  - Variations in sensitivity to radiation-induced mammary cancer among different
      strains of mice are well known. However, the reasons for these variations have
      not been determined. In the present study, the cell dissociation assay was used
      to determine the radiation-induced transformation frequencies in sensitive BALB/c
      mice and resistant C57BL mice as well as the resistant hybrid B6CF1 independent
      of host environment. The influence of host environment on the progression of
      transformed cells to the neoplastic phenotype was also examined. Results
      demonstrated that the variations in sensitivity among these sensitive and
      resistant mice are a result of inherent differences in the sensitivity of the
      mammary epithelial cells to radiation-induced transformation. Under the
      conditions used, host environment played no role in the initiation of transformed
      cells by radiation or in the progression of these cells to the neoplastic
      phenotype.

PMID- 8752317
TI  - Comment on "Incidence of salivary gland tumors among atomic bomb survivors, 1950
      1987. Evaluation of radiation-related risk" by Land et al. (Radiat. Res. 146, 28
      36, 1996)

PMID- 8752318
TI  - Lung cancer risks: comparing radiation with tobacco.

PMID- 8752319
TI  - The archaeal flagellum: a unique motility structure.

PMID- 8752320
TI  - A modular family 19 chitinase found in the prokaryotic organism Streptomyces
      griseus HUT 6037.
AB  - The specificity of chitinase C-1 of Streptomyces griseus HUT 6037 for the
      hydrolysis of the beta-1,4-glycosidic linkages in partially acetylated chitosan
      is different from that of other microbial chitinases. In order to study the
      primary structure of this unique chitinase, the chiC gene specifying chitinase C
      1 was cloned and its nucleotide sequence was determined. The gene encodes a
      polypeptide of 294 amino acids with a calculated size of 31.4 kDa. Comparison of
      the amino acid sequence of the deduced polypeptide with that of other proteins
      revealed a C-terminal catalytic domain displaying considerable sequence
      similarity to the catalytic domain of plant class I, II, and IV chitinases which
      form glycosyl hydrolase family 19. The N-terminal domain of the deduced
      polypeptide exhibits sequence similarity to substrate-binding domains of several
      microbial chitinases and cellulases but not to the chitin-binding domains of
      plant chitinases. The previously purified chitinase C-1 from S. griseus is
      suggested to be generated by proteolytic removal of the N-terminal chitin-binding
      domain and corresponds to the catalytic domain of the chitinase encoded by the
      chiC gene. High-performance liquid chromatography analysis of the hydrolysis
      products from N-acetyl chitotetraose revealed that chitinase C-1 catalyzes
      hydrolysis of the glycosidic bond with inversion of the anomeric configuration,
      in agreement with the previously reported inverting mechanism of plant class I
      chitinases. This is the first report of a family 19 chitinase found in an
      organism other than higher plants.

PMID- 8752321
TI  - Three transport systems for the osmoprotectant glycine betaine operate in
      Bacillus subtilis: characterization of OpuD.
AB  - The accumulation of the osmoprotectant glycine betaine from exogenous sources
      provides a high degree of osmotic tolerance to Bacillus subtilis. We have
      identified, through functional complementation of an Escherichia coli mutant
      defective in glycine betaine uptake, a new glycine betaine transport system from
      B. subtilis. The DNA sequence of a 2,310-bp segment of the cloned region revealed
      a single gene (opuD) whose product (OpuD) was essential for glycine betaine
      uptake and osmoprotection in E. coli. The opuD gene encodes a hydrophobic 56.13
      kDa protein (512 amino acid residues). OpuD shows a significant degree of
      sequence identity to the choline transporter BetT and the carnitine transporter
      CaiT from E. coli and a BetT-like protein from Haemophilus influenzae. These
      membrane proteins form a family of transporters involved in the uptake of
      trimethylammonium compounds. The OpuD-mediated glycine betaine transport activity
      in B. subtilis is controlled by the environmental osmolarity. High osmolarity
      stimulates de novo synthesis of OpuD and activates preexisting OpuD proteins to
      achieve maximal glycine betaine uptake activity. An opuD mutant was constructed
      by marker replacement, and the OpuD-mediated glycine betaine uptake activity was
      compared with that of the previously identified multicomponent OpuA and OpuC
      (ProU) glycine betaine uptake systems. In addition, a set of mutants was
      constructed, each of which synthesized only one of the three glycine betaine
      uptake systems. These mutants were used to determine the kinetic parameters for
      glycine betaine transport through OpuA, OpuC, and OpuD. Each of these uptake
      systems shows high substrate affinity, with Km values in the low micromolar
      range, which should allow B. subtilis to efficiently acquire the osmoprotectant
      from the environment. The systems differed in their contribution to the overall
      glycine betaine accumulation and osmoprotection. A triple opuA, opuC, and opuD
      mutant strain was isolated, and it showed no glycine betaine uptake activity,
      demonstrating that three transport systems for this osmoprotectant operate in B.
      subtilis.

PMID- 8752322
TI  - Interaction between FtsZ and inhibitors of cell division.
AB  - The interaction between inhibitors of cell division and FtsZ were assessed by
      using the yeast two-hybrid system. An interaction was observed between FtsZ and
      SulA, a component of the SOS response, and the interacting regions were mapped to
      their conserved domains. This interaction was reduced by mutations in sulA and by
      most mutations in ftsZ that make cell refractory to sulA. No interaction was
      detected between FtsZ and MinCD, an inhibitory component of the site selection
      system. However, interactions were observed among various members of the Min
      system, and MinE was found to reduce the interaction between MinC and MinD. The
      implications of these findings for cell division are discussed.

PMID- 8752323
TI  - The C terminus of the AddA subunit of the Bacillus subtilis ATP-dependent DNase
      is required for the ATP-dependent exonuclease activity but not for the helicase
      activity.
AB  - Comparison of subunit AddA of the Bacillus subtilis AddAB enzyme, subunit RecB of
      the Escherichia coli RecBCD enzyme, and subunit RecB of the Haemophilus
      influenzae RecBCD enzyme revealed several regions of homology. Whereas the first
      seven regions are common among helicases, the two C-terminally located regions
      are unique for RecB of E. coli and H. influenzae and AddA. Deletion of the C
      terminal region resulted in the production of an enzyme which showed moderately
      impaired levels of ATP-dependent helicase activity, whereas the ATP-dependent
      exonuclease activity was completely destroyed. The mutant enzyme was almost
      completely capable of complementing E. coli recBCD and B. subtilis addAB strains
      with respect to DNA repair and homologous recombination. These results strongly
      suggest that at least part of the C-terminal region of the AddA protein is
      indispensable for exonuclease activity and that, in contrast to the exonuclease
      activity, the helicase activity of the addAB gene product is important for DNA
      repair and homologous recombination.

PMID- 8752325
TI  - Identification of a new inhibitor of essential division gene ftsZ as the kil gene
      of defective prophage Rac.
AB  - A gene function carried by a plasmid, causing arrest of cell division in
      Escherichia coli, has been identified as the product of a short open reading
      frame of the prophage Rac, previously designated orfE, expressed only under
      conditions of prophage induction. Because Rac carries a killing function
      expressed under conditions of zygotic induction, an orfE-defective Rac+ strain
      was constructed. This strain had lost the killing function, indicating that orfE
      is kil. Division inhibition by kil was specifically relieved by overexpression of
      essential division gene ftsZ. The kil gene product acts independently of the min
      operon, and its effects are increased in conditions of high cyclic AMP (cAMP)
      receptor protein-cAMP complex levels in the cell. Furthermore, at high levels of
      expression, kil product distorts the rod shape of the cells. These features
      distinguish kil-encoded protein from the inhibitory product of gene dicB, which
      occupies a similar genetic location in Kim (Qin), another defective prophage of
      Escherichia coli.

PMID- 8752324
TI  - Molecular basis of the magnesium deprivation response in Salmonella typhimurium:
      identification of PhoP-regulated genes.
AB  - The PhoP-PhoQ two-component system is essential for virulence in Salmonella
      typhimurium. This system controls expression of some 40 different proteins, yet
      most PhoP-regulated genes remain unknown. To identify PhoP-regulated genes, we
      isolated a library of 50,000 independent lac gene transcriptional fusion strains
      and investigated whether production of beta-galactosidase was regulated by PhoP.
      We recovered 47 lac gene fusions that were activated and 7 that were repressed
      when PhoP was expressed. Analysis of 40 such fusions defined some 30 loci,
      including mgtA and mgtCB, which encode two of the three Mg2+ uptake systems of S.
      typhimurium; ugd, encoding UDP-glucose dehydrogenase; phoP, indicative that the
      phoPQ operon is autoregulated; and an open reading frame encoding a protein with
      sequence similarity to VanX, a dipeptidase required for resistance to vancomycin.
      Transcription of PhoP-activated genes was regulated by the levels of Mg2+ in a
      PhoP-dependent manner. Strains with mutations in phoP or phoQ were defective for
      growth in low-Mg2+ media. The mgtA and mgtCB mutants reached lower optical
      densities than the wild-type strain in low-Mg2+ liquid media but displayed normal
      growth on low-Mg2+ solid media. Six PhoP-activated genes were identified as
      essential to form colonies on low-Mg'+ solid media. Cumulatively, our experiments
      establish that the PhoP-PhoQ system governs the adaptation to magnesium-limiting
      environments.

PMID- 8752326
TI  - Generation of an endogenous DNA-methylating agent by nitrosation in Escherichia
      coli.
AB  - Escherichia coli ada ogt mutants, which are totally deficient in O6-methylguanine
      DNA methyltransferases, have an increased spontaneous mutation rate. This
      phenotype is particularly evident in starving cells and suggests the generation
      of an endogenous DNA alkylating agent under this growth condition. We have found
      that in wild-type cells, the level of the inducible Ada protein is 20-fold higher
      in stationary-phase and starving cells than in rapidly growing cells, thus
      enhancing the defense of these cells against DNA damage. The increased level of
      Ada in stationary cells is dependent on RpoS, a stationary-phase-specific sigma
      subunit of RNA polymerase. We have also identified a potential source of the
      mutagenic agent. Nitrosation of amides and related compounds can generate
      directly acting methylating agents and can be catalyzed by bacteria] enzymes. E.
      coli moa mutants, which are defective in the synthesis of a molybdopterin
      cofactor required by several reductases, are deficient in nitrosation activity.
      It is reported here that a moa mutant shows reduced generation of a mutagenic
      methylating agent from methylamine (or methylurea) and nitrite added to agar
      plates. Moreover, a moa mutation eliminates much of the spontaneous mutagenesis
      in ada ogt mutants. These observations indicate that the major endogenous mutagen
      is not S-adenosylmethionine but arises by bacterially catalyzed nitrosation.

PMID- 8752327
TI  - Identification of sigma S-regulated genes in Salmonella typhimurium:
      complementary regulatory interactions between sigma S and cyclic AMP receptor
      protein.
AB  - sigma S (RpoS)-regulated lacZ transcriptional fusions in Salmonella typhimurium
      were identified from a MudJ transposon library by placing the rpoS gene under the
      control of the araBAD promoter and detecting lacZ expression in the presence or
      absence of arabinose supplementation. Western blot (immunoblot) analysis of
      bacteria carrying PBAD::rpoS demonstrated arabinose-dependent rpoS expression
      during all phases of growth. sigma S-dependent gene expression of individual gene
      fusions was confirmed by P22-mediated transduction of the MudJ insertions into
      wild-type or rpoS backgrounds. Analysis of six insertions revealed the known
      sigma S-regulated gene otsA, as well as five novel loci. Each of these genes is
      maximally expressed in stationary phase, and all but one show evidence of cyclic
      AMP receptor protein-dependent repression during logarithmic growth which is
      relieved in stationary phase. For these genes, as well as for the sigma S
      regulated spvB plasmid virulence gene, a combination of rpoS overexpression and
      crp inactivation can result in high-level expression during logarithmic growth.
      The approach used to identify sigma S-regulated genes in this study provides a
      general method for the identification of genes controlled by trans-acting
      regulatory factors.

PMID- 8752329
TI  - Effects of lysine-to-glycine mutations in the ATP-binding consensus sequences in
      the AddA and AddB subunits on the Bacillus subtilis AddAB enzyme activities.
AB  - The N-terminal regions of both subunits AddA and AddB of the Bacillus subtilis
      AddAB enzyme contain amino acid sequences, designated motif I, which are commonly
      found in ATP-binding enzymes. The functional significance of the motif I regions
      was studied by replacing the highly conserved lysine residues of the regions in
      both subunits by glycines and by examination of the resulting mutant enzymes with
      respect to their enzymatic properties. This study shows that the mutation in
      subunit AddB hardly affected the ATPase, helicase, and exonuclease activities of
      the AddAB enzyme. However, the mutation in subunit AddA drastically reduced these
      activities, as well as the kcat for ATP hydrolysis. The apparent Km for ATP in
      ATP hydrolysis did not significantly deviate from that of the wild-type enzyme.
      These results suggest that the lysine residue in motif I of subunit AddA of the
      AddAB enzyme is not essential for the binding of the nucleotide but has a role in
      ATP hydrolysis, which is required for the exonuclease and helicase activities of
      the enzyme.

PMID- 8752328
TI  - Synthesis of the osmoprotectant glycine betaine in Bacillus subtilis:
      characterization of the gbsAB genes.
AB  - Synthesis of the osmoprotectant glycine betaine from the exogenously provided
      precursor choline or glycine betaine aldehyde confers considerable osmotic stress
      tolerance to Bacillus subtilis in high-osmolarity media. Using an Escherichia
      coli mutant (betBA) defective in the glycine betaine synthesis enzymes, we cloned
      by functional complementation the genes that are required for the synthesis of
      the osmoprotectant glycine betaine in B. subtilis. The DNA sequence of a 4.1-kb
      segment from the cloned chromosomal B. subtilis DNA was established, and two
      genes (gbsA and gbsB) whose products were essential for glycine betaine
      biosynthesis and osmoprotection were identified. The gbsA and gbsB genes are
      transcribed in the same direction, are separated by a short intergenic region,
      and are likely to form an operon. The deduced gbsA gene product exhibits strong
      sequence identity with members of a superfamily of specialized and nonspecialized
      aldehyde dehydrogenases. This superfamily comprises glycine betaine aldehyde
      dehydrogenases from bacteria and plants with known involvement in the cellular
      adaptation to high-osmolarity stress and drought. The deduced gbsB gene product
      shows significant similarity to the family of type III alcohol dehydrogenases. B.
      subtilis mutants with defects in the chromosomal gbsAB genes were constructed by
      marker replacement, and the growth properties of these mutant strains in high
      osmolarity medium were analyzed. Deletion of the gbsAB genes destroyed the
      choline-glycine betaine synthesis pathway and abolished the ability of B.
      subtilis to deal effectively with high-osmolarity stress in choline- or glycine
      betaine aldehyde-containing medium. Uptake of radiolabelled choline was unaltered
      in the gbsAB mutant strain. The continued intracellular accumulation of choline
      or glycine betaine aldehyde in a strain lacking the glycine betaine-biosynthetic
      enzymes strongly interfered with the growth of B. subtilis, even in medium of
      moderate osmolarity. A single transcription initiation site for gbsAB was
      detected by high-resolution primer extension analysis. gbsAB transcription was
      initiated from a promoter with close homology to sigma A-dependent promoters and
      was stimulated by the presence of choline in the growth medium.

PMID- 8752330
TI  - asmB, a suppressor locus for assembly-defective OmpF mutants of Escherichia coli,
      is allelic to envA (lpxC).
AB  - A novel genetic scheme allowed us to isolate extragenic suppressor mutations that
      restored mutant OmpF assembly. One group of these mutations, termed asmB for
      assembly suppressor mutation B, permitted mutant OmpF assembly in a non-allele
      specific manner. Genetic mapping analyses placed the asmB mutations at the 2-min
      region of the Escherichia coli K-12 chromosome. Further analyses revealed that
      the asmB mutations map within the envA (lpxC) gene, which encodes an enzyme
      needed for the synthesis of the lipid A moiety of lipopolysaccharide (LPS).
      Nucleotide sequence analysis showed that the asmB mutations caused a change from
      F-50 to S (F50S substitution) (asmB2 and asmB3) or a G210S substitution (asmB1)
      in EnvA. Cells bearing the asmB alleles displayed increased sensitivity to
      various hydrophobic compounds and detergents, suggesting an alteration within the
      outer membrane. Direct examination (of the LPS showed that its amounts were
      reduced by the asmB mutations, with asmB1 exerting a greater effect than asmB2 or
      asmB3. Thus, it appears that the asmB mutations achieve mutant OmpF assembly
      suppression by reducing LPS levels, which in turn may alter membrane fluidity.

PMID- 8752331
TI  - Plasmid-amplified comS enhances genetic competence and suppresses sinR in
      Bacillus subtilis.
AB  - The establishment of genetic competence in Bacillus subtilis is controlled by a
      vast signal transduction network involving the products of genes that function in
      several postexponential-phase processes. Two of these proteins, SinR and DegU,
      serve as molecular switches that influence a cell's decision to undergo either
      sporulation or genetic competence development. In order to determine the roles of
      SinR and DegU in competence control, multicopy suppression experiments with
      plasmid-amplified comS, SinR, and degU genes were undertaken. Multicopy comS was
      found to elevate competence gene transcription and transformation efficiency in
      both wild-type and sinR mutant cells but not in degU mutant cells. Multicopy degU
      failed to suppress comS or sinR mutations. No suppression of comS or degU by
      multicopy sinR was observed. The expression of a comS'::'lacZ translational
      fusion and srf-lacZ operon fusion was examined in sinR cells and cells bearing
      plasmid-amplified sinR. The expression of comS'::'lacZ gene fusion was reduced by
      the sinR mutation, but both comS'::'lacZ and srf-lacZ were repressed by multicopy
      sinR. Cells bearing plasmid-amplified sinR were poorly competent. These results
      suggest that sinR is required for optimal comS expression but not transcription
      from the srf promoter and that SinR at high concentrations represses srf
      transcription initiation.

PMID- 8752332
TI  - A methyl-accepting protein involved in multiple-sugar chemotaxis by Cellulomonas
      gelida.
AB  - Tethered-cell and capillary assays indicated that L-methionine is required by
      Cellulomonas gelida for its normal cell motility pattern and chemotaxis and that
      S-adenosylmethionine is involved in sugar chemotaxis by this cellulolytic
      bacterium. In addition, in vivo methylation assays showed that several proteins
      were methylated in the absence of protein synthesis. The incorporated methyl
      groups were alkali sensitive. Of special interest was the observation that the
      methylation level of a 51,000-Mr protein increased two- to fivefold upon addition
      of various sugar attractants and decreased after the removal of the attractants.
      The increase was less pronounced in mutants defective in sugar chemotaxis and
      appeared to be specifically involved with sugar chemotaxis. Furthermore, cell
      fractionation and in vitro methylation assays demonstrated that the 51,000-Mr
      protein is located in the cytoplasmic membrane. These results suggest that a
      specific methyl-accepting chemotaxis protein is involved in multiple-sugar
      chemotaxis by C gelida. During chemotaxis, the changes of methylesterase activity
      in C gelida cells were similar to those in Escherichia coli RP437 cells, as
      determined by a continuous-flow assay for methanol evolution. Thus, the mechanism
      of methyl-accepting chemotaxis protein-mediated chemotaxis of the gram-positive
      C. gelida appears to be similar to that of the gram-negative E. coli rather than
      to that of other gram-positive bacteria, such as Bacillus subtilis.

PMID- 8752333
TI  - Interaction of the trp RNA-Binding attenuation protein (TRAP) of Bacillus
      subtilis with RNA: effects of the number of GAG repeats, the nucleotides
      separating adjacent repeats, and RNA secondary structure.
AB  - The 11-subunit trp RNA-binding attenuation protein of Bacillus subtilis, TRAP,
      regulates transcription and translation by binding to several (G/U)AG repeats
      present in the trp leader and trpG transcripts. Filter binding assays were used
      to study interactions between L-tryptophan-activated TRAP and synthetic RNAs.
      RNAs that contained GAG and/or UAG repeats were tested while the length and
      sequence of the nucleotides separating adjacent trinucleotide repeats were
      altered. TRAP-RNA complexes formed with transcripts containing GAG repeats were
      more stable than those with transcripts containing UAG repeats or alternating GAG
      and UAG repeats. The stability of TRAP-RNA complexes also increased substantially
      when the number of GAG repeats was increased from five to six and from six to
      seven. A gradual increase in complex stability was observed when the number of
      GAG repeats was increased from 7 to 11. The optimal spacer between adjacent
      trinucleotide repeats was found to be 2 nucleotides, with A and U residues
      preferred over G and C residues. TRAP binding was specific for single-stranded
      RNA; TRAP could not bind to RNA containing GAG repeats base paired in a stable
      RNA duplex. Overall, our findings suggest that each L-tryptophan-activated TRAP
      subunit can bind one (G/U)AG repeat and that multiple TRAP subunit-RNA binding
      site interactions are required for stable TRAP-RNA association.

PMID- 8752334
TI  - A resolvase-like protein is required for the site-specific integration of the
      temperate lactococcal bacteriophage TP901-1.
AB  - The integration system of the temperate lactococcal phage TP901-1 was
      characterized in Lactococcus lactis subsp. cremoris LM0230 and MG1363 with the
      use of deletion derivatives of the integration vector pBC143 (B. Christiansen, M.
      G. Johnsen, E. Stenby, F. K. Vogensen, and K. Hammer, J. Bacteriol. 176:1069
      1076, 1994). The phage-encoded elements necessary for integration were localized
      on a 2.8-kb NsiI-EcoRI fragment including the phage attachment site, attP. This
      fragment was DNA sequenced, and sequence analysis revealed three putatively
      expressed open reading frames, Orf1, Orf2, and Orf3 By the introduction of
      mutations within the orf1, orf2, and orf3 genes, it was shown that only Orf1 was
      necessary for the integration process. Furthermore, it was found that Orf1, attP,
      and a 425-bp region upstream of the orf1 gene are sufficient for integration.
      Orf1 contains 485 amino acids and is located just upstream of attP. The N
      terminal 150 to 180 amino acids of Orf1 showed 38 to 44% similarity to the
      resolvase group of site-specific integrases, while no similarity to known
      proteins was found in the C-terminal end. Bacteriophage TP901-1 therefore
      contains a unique integration system that does not resemble the Int class of site
      specific integrases usually found in temperate bacteriophages. The constructed
      integration vector, pBC170, integrates into the chromosomal attachment site very
      efficiently and forms stable transformants with a frequency corresponding to 20%
      of the transformation efficiency.

PMID- 8752335
TI  - The hupTUV operon is involved in negative control of hydrogenase synthesis in
      Rhodobacter capsulatus.
AB  - The hupT, hupU, and hupV genes, which are located upstream from the hupSLC and
      hypF genes in the chromosome of Rhodobacter capsulatus, form the hupTUV operon
      expressed from the hupT promoter. The hupU and hupV genes, previously thought to
      belong to a single open reading frame, encode HupU, of 34.5 kDa (332 amino
      acids), and HupV, of 50.4 kDa (476 amino acids), which are >/= 50% identical to
      the homologous Bradyrhizobium japonicum HupU and HupV proteins and Rhodobacter
      sphaeroides HupU1 and HupU2 proteins, respectively; they also have 20 and 29%
      similarity with the small subunit (HupS) and the large subunit (HupL),
      respectively, of R. capsulatus [NiFe]hydrogenase. HupU lacks the signal peptide
      of HupS and HupV lacks the C-terminal sequence of HupL, which are cleaved during
      hydrogenase processing. Inactivation of hupV by insertional mutagenesis or of
      hupUV by in-frame deletion led to HupV- and Hup(UV)- mutants derepressed for
      hydrogenase synthesis, particularly in the presence of oxygen. These mutants were
      complemented in trans by plasmid-borne hupTUV but not by hupT or by hupUV, except
      when expressed from the inducible fru promoter. Complementation of the HupV- and
      Hup(UV)- mutants brought about a decrease in hydrogenase activity up to 10-fold,
      to the level of the wild-type strain B10, indicating that HupU and HupV
      participate in negative regulation of hydrogenase expression in concert with
      HupT, a sensor histidine kinase involved in the repression process. Plasmid-borne
      gene fusions used to monitor hupTUV expression indicated that the operon is
      expressed at a low level (50- to 100-fold lower than hupS).

PMID- 8752336
TI  - A positive control mutant of the transcription activator protein FIS.
AB  - The FIS protein is a transcription activator of rRNA and other genes in
      Escherichia coli. We have identified mutants of the FIS protein resulting in
      reduced rrnB P1 transcription activation that nevertheless retain the ability to
      bind DNA in vivo. The mutations map to amino acid 74, the N-terminal amino acid
      of the protein's helix-turn-helix DNA binding motif, and to amino acids 71 and 72
      in the adjoining surface-exposed loop. In vitro analyses of one of the activation
      defective mutants (with a G-to-S mutation at position 72) indicates that it binds
      to and bends rrnB P1 FIS site I DNA the same as wild-type FIS. These data suggest
      that amino acids in this region of FIS are required for transcription activation
      by contacting RNA polymerase directly, independent of any other role(s) this
      region may play in DNA binding or protein-induced bending.

PMID- 8752337
TI  - Identification and characterization of additional flagellin genes from Vibrio
      anguillarum.
AB  - Previously, the flagellar filament of Vibrio anguillarum was suggested to consist
      of flagellin A and three additional flagellin proteins, FlaB, -C, and -D. This
      study identifies the genes encoding FlaB, -C, and -D and a possible fifth
      flagellin gene that may encode FlaE. The flagellin genes map at two separate DNA
      loci and are most similar to the four polar flagellin genes of Vibrio
      parahaemolyticus, also located at two DNA loci. The genetic organization of these
      two loci is conserved between both organisms. For each gene, in-frame deletions
      of the entire gene, the 5' end, and the 3' end were made. Mutant analysis showed
      that each mutation, except those in flaE, caused a loss of flagellin from the
      filament. However, no obvious structural loss in the filament, as determined by
      electron microscopy, and only slight decreases in motility were seen. Virulence
      analysis indicated that all but two of the mutations gave a wild-type phenotype.
      The 5'-end deletions of flaD and flaE decreased virulence significantly (>10(4)
      fold) of infections via both the intraperitoneal and immersion routes. These
      results indicate that, like FlaA, FlaD and FlaE may also be involved in
      virulence.

PMID- 8752338
TI  - Oxygen taxis and proton motive force in Azospirillum brasilense.
AB  - The microaerophilic nitrogen-fixing bacterium Azospirillum brasilense formed a
      sharply defined band in a spatial gradient of oxygen. As a result of aerotaxis,
      the bacteria were attracted to a specific low concentration of oxygen (3 to 5
      microM). Bacteria swimming away from the aerotactic band were repelled by the
      higher or lower concentration of oxygen that they encountered and returned to the
      band. This behavior was confirmed by using temporal gradients of oxygen. The
      cellular energy level in A. brasilense, monitored by measuring the proton motive
      force, was maximal at 3 to 5 microM oxygen. The proton motive force was lower at
      oxygen concentrations that were higher or lower than the preferred oxygen
      concentration. Bacteria swimming toward the aerotactic band would experience an
      increase in the proton motive force, and bacteria swimming away from the band
      would experience a decrease in the proton motive force. It is proposed that the
      change in the proton motive force is the signal that regulates positive and
      negative aerotaxis. The preferred oxygen concentration for aerotaxis was similar
      to the preferred oxygen concentration for nitrogen fixation. Aerotaxis is an
      important adaptive behavioral response that can guide these free-living
      diazotrophs to the optimal niche for nitrogen fixation in the rhizosphere.

PMID- 8752339
TI  - Clonally diverse rfb gene clusters are involved in expression of a family of
      related D-galactan O antigens in Klebsiella species.
AB  - Klebsiella species express a family of structurally related lipopolysaccharide O
      antigens which share a common backbone known as D-galactan I. Serotype
      specificity results from modification of D-galactan I by addition of domains of
      altered structure or by substitution with O-acetyl and/or alpha-D-Galp side
      groups with various linkages and stoichiometries. In the prototype, Klebsiella
      serotype O1, the his-linked rfb gene cluster is required for synthesis of D
      galactan I, but genes conferring serotype specificity are unlinked. The D
      galactan I part of the O polysaccharide is O acetylated in Klebsiella serotype
      O8. By cloning the rfb region from Klebsiella serotype O8 and analyzing the O
      polysaccharide synthesized in Escherichia coli K-12 hosts, we show that, like
      rfbO1, the rfbO8 region directs formation of unmodified D-galactan I. The rfbAB
      genes encode an ATP-binding cassette transporter required for export of polymeric
      D-galactan I across the plasma membrane prior to completion of the
      lipopolysaccharide molecule by ligation of the O polysaccharide to lipid A-core.
      Complementation experiments show that the rfbAB gene products in serotypes O1 and
      O8 are functionally equivalent and interchangeable. Hybridization experiments and
      physical mapping of the rfb regions in related Klebsiella serotypes suggest the
      existence of shared rfb genes with a common organization. However, despite the
      functional equivalence of these rfb gene clusters, at least three distinct clonal
      groups were detected in different Klebsiella species and subspecies, on the basis
      of Southern hybridization experiments carried out under high-stringency
      conditions. The clonal groups cannot be predicted by features of the O-antigen
      structure. To examine the relationships in more detail, the complete nucleotide
      sequence of the serotype O8 rfb cluster was determined and compared with that of
      the serotype O1 prototype. The nucleotide sequences for the six rfb genes showed
      variations in moles percent G+C values and in the values for nucleotide sequence
      identity, which ranged from 66.9 to 79.7%. The predicted polypeptides ranged from
      64.3% identity (78.4% total similarity) to 94.3% identity (98.0% similarity). The
      results presented here are not consistent with dissemination of the Klebsiella D
      galactan I rfb genes through recent lateral transfer events.

PMID- 8752341
TI  - An 18-base-pair sequence is sufficient for termination of rolling-circle
      replication of plasmid pT181.
AB  - pT181 and related plasmids of gram-positive bacteria replicate by a rolling
      circle mechanism. The replication initiator protein of pT181, RepC, has origin
      specific nicking-closing activities. Replication of the plasmid pT181 leading
      strand initiates by covalent extension of the RepC-generated nick, and the origin
      of replication contains signals for both initiation and termination of DNA
      replication. We have investigated the sequence requirements for the initiation
      and termination steps by using plasmids containing two pT181 origins. In vitro
      replication experiments showed that 18- and 24-bp synthetic oligonucleotides
      containing the RepC nick site were active in the termination of replication.
      However, initiation of replication required a larger region which also includes
      the RepC binding site. Plasmids containing the 18- and 24-bp region were also
      found to be nicked by the RepC protein. Our results demonstrate that sequence
      requirements for initiation and termination of pT181 replication overlap, but
      while the RepC binding site is required for initiation, it is dispensable for
      termination.

PMID- 8752340
TI  - Regulation of glycerol metabolism in Pseudomonas aeruginosa: characterization of
      the glpR repressor gene.
AB  - The operons of the glp regulon encoding the glycerol metabolic enzymes of
      Pseudomonas aeruginosa were hitherto believed to be positively regulated by the
      product of the glpR regulatory gene. During nucleotide sequence analysis of the
      region located upstream of the previously characterized glpD gene, encoding sn
      glycerol-3-phosphate dehydrogenase, an open reading frame (glpR) was identified
      which encodes a protein of 251 amino acids that is 59% identical to the Glp
      repressor from Escherichia coli and could be expressed as a 28-kDa protein in a
      T7 expression system. Inactivation of chromosomal glpR by gene replacement
      resulted in constitutive expression of glycerol transport activity and glpD
      activity. These activities were strongly repressed after introduction of a
      multicopy plasmid containing the glpR gene; the same plasmid also efficiently
      repressed expression of a glpT-lacZ+ transcriptional fusion in an E. coli glpR
      mutant. Analysis of the glpD and glpF upstream region identified conserved
      palindromic sequences which were 70% identical to the E. coli glp operator
      consensus sequence. The results suggest that the operons of the glp regulon in P.
      aeruginosa are negatively regulated by the action of a glp repressor.

PMID- 8752342
TI  - Isolation, characterization, and expression of the Corynebacterium glutamicum
      betP gene, encoding the transport system for the compatible solute glycine
      betaine.
AB  - Corynebacterium glutamicum accumulates glycine betaine under conditions of high
      osmolarity. Previous work revealed the existence of a high-affinity glycine
      betaine permease which is osmotically regulated. In the present study, the
      corresponding gene was cloned. The betP gene, encoding the glycine betaine uptake
      carrier, was isolated by heterologous complementation of mutant strain
      Escherichia coli MKH13. From sequence analysis it is predicted to encode a
      protein of 595 amino acids. This protein shares 36% identity with the choline
      transport system BetT and 28% identity with the carnitine transport system CaiT
      of E. coli, as well as 38% identity with a protein with an unknown function from
      Haemophilus influenzae. Analysis of hydropathy indicated a common structure for
      all four transport proteins. After heterologous expression of betP in E. coli
      MKH13, the measured Km values for glycine betaine and the cotransported Na+ were
      similar to those found in C. glutamicum, whereas the modulation of activity by
      osmotic gradients was shifted to lower osmotic values.

PMID- 8752343
TI  - The expression of a plasmid-specified exported protein causes structural plasmid
      instability in Bacillus subtilis.
AB  - The rolling-circle plasmid pGP1 was used to study the effects of the expression
      of a plasmid-specified exported protein on structural plasmid stability in
      Bacillus subtilis. pGP1 contains a fusion between the Bacillus licheniformis penP
      gene, encoding a C-terminally truncated penicillinase, and the Escherichia coli
      beta-galactosidase (lacZ) gene. Two processes affected the accumulation of pGP1
      variants with deletions in the penP-lacZ region. First, divergent transcription
      from genes upstream of penP-lacZ increased pGP1 deletion frequencies up to about
      10-fold. Second, the removal of the PenP signal peptide resulted in completely
      stable plasmids, indicating that the entry of the PenP fragment into the protein
      export pathway is an important factor in the instability of pGP1. On the basis of
      these results, we propose a model in which the temporary anchoring of the plasmid
      to the membrane through the cotranscriptional and cotranslational entry of PenP
      into the protein export pathway creates domains of local hypersupercoiling, which
      we assume to be targets for deletion formation.

PMID- 8752344
TI  - Characterization of methyltransferase and hydroxylase genes involved in the
      biosynthesis of the immunosuppressants FK506 and FK520.
AB  - FK506 and FK520 are 23-membered macrocyclic polyketides with potent
      immunosuppressive and antifungal activities. The gene encoding 31-O-demethyl
      FK506 methyltransferase, fkbM, was isolated from Streptomyces sp. strains MA6858
      and MA6548, two FK506 producers, and Streptomyces hygroscopicus subsp.
      ascomyceticus, an FK520 producer. The nucleotide sequence of the fkbM gene
      revealed an open reading frame encoding a polypeptide of 260 amino acids.
      Disruption of fkbM in Streptomyces sp. strain MA6548 yielded a mutant that
      produced 31-O-demethyl-FK506, confirming the involvement of the isolated genes in
      the biosynthesis of FK506 and FK520. Heterologous expression of fkbM in
      Streptomyces lividans established that fkbM encodes an O-methyltransferase
      catalyzing the methylation of the C-31 hydroxyl group of 31-O-demethyl-FK506 and
      FK520. A second open reading frame, fkbD, was found upstream of fkbM in all three
      aforementioned species and was predicted to encode a protein of 388 residues that
      showed a strong resemblance to cytochrome P-450 hydroxylases. Disruption of fkbD
      had a polar effect on the synthesis of the downstream fkbM gene product and
      resulted in the formation of 9-deoxo-31-O-demethyl-FK506. This established the
      product of fkbD as the cytochrome P-450 9-deoxo-FK506 hydroxylase, which is
      responsible for hydroxylation at position C-9 of the FK506 and FK520 macrolactone
      ring.

PMID- 8752345
TI  - Catechol dioxygenases from Escherichia coli (MhpB) and Alcaligenes eutrophus
      (MpcI): sequence analysis and biochemical properties of a third family of
      extradiol dioxygenases.
AB  - The nucleotide sequence of the Escherichia coli mhpB gene, encoding 2,3
      dihydroxyphenylpropionate 1,2-dioxygenase, was determined by sequencing of a 3.1
      kb fragment of DNA from Kohara phage 139. The inferred amino acid sequence showed
      58% sequence identity with the sequence of an extradiol dioxygenase, MpcI, from
      Alcaligenes eutrophus and 10 to 20% sequence identity with protocatechuate 4,5
      dioxygenase from Pseudomonas paucimobilis, with 3,4-dihydroxyphenylacetate 2,3
      dioxygenase from E. coli, and with human 3-hydroxyanthranilate dioxygenase.
      Sequence similarity between the N- and C-terminal halves of this new family of
      dioxygenases was detected, with conserved histidine residues in the N-terminal
      domain. A model is proposed to account for the relationship between this family
      of enzymes and other extradiol dioxygenases. The A. eutrophus MpcI enzyme was
      expressed in E. coli, purified, and characterized as a protein with a subunit
      size of 33.8 kDa. Purified MhpB and MpcI showed similar substrate specificities
      for a range of 3-substituted catechols, and evidence for essential histidine and
      cysteine residues in both enzymes was obtained.

PMID- 8752346
TI  - Identification of a Cryptococcus neoformans gene that directs expression of the
      cryptic Saccharomyces cerevisiae mannitol dehydrogenase gene.
AB  - The Mtl gene from Cryptococcus neoformans, which confers the ability of
      Saccharomyces cerevisiae Sc4l YJO to grow on mannitol with substantial NAD
      dependent mannitol dehydrogenase activity, was identified. Purifications and
      characterizations of this enzyme show that it is found in polyploid strain BB1,
      and the peptide sequence of the enzyme helped identify the saccharomyces gene
      encoding this mannitol dehydrogenase activity. On the other hand, the Mtl gene of
      C. neoformans encodes a 346-amino-acid protein which is not mannitol
      dehydrogenase but a regulatory element which is active in a heterologous fungus.

PMID- 8752347
TI  - Isolation, purification, and in vitro characterization of recessive-lethal-mutant
      RNA polymerases from Escherichia coli.
AB  - The beta subunit of prokaryotic RNA polymerase shares significant sequence
      similarity with its eukaryotic and archaeal counterparts across most of the
      protein. Nine segments of particularly high similarity have been identified and
      are termed segments A through I. We have isolated severely defective Escherichia
      coli RNA polymerase mutants, most of which are unable to support bacterial
      growth. The majority of the substitutions affect residues in one of the conserved
      segments of beta, including invariant residues in segments D (amino acids 548 to
      577), E (amino acids 660 to 678), and I (amino acids 1198 to 1296). In addition,
      recessive-lethal mutations that affect residues highly conserved only among
      prokaryotes were identified. They include a substitution in the extreme amino
      terminus of beta, a region in which no substitutions have previously been
      identified, and one rpoB mutation that truncates the polypeptide without
      abolishing minimal polymerase function in vitro. To examine the recessive-lethal
      alleles in vitro, we devised a novel method to remove nonmutant enzyme from RNA
      polymerase preparations by affinity tagging the chromosomal rpoB gene. In vitro
      examination of a subset of purified recessive-lethal RNA polymerases revealed
      that several substitutions, including all of those altering conserved residues in
      segment I, severely decrease transcript elongation and increase termination. We
      discuss the insights these mutants lend to a structure-function analysis of RNA
      polymerase.

PMID- 8752348
TI  - Evidence that the PBP 5 synthesis repressor (psr) of Enterococcus hirae is also
      involved in the regulation of cell wall composition and other cell wall-related
      properties.
AB  - psr has been reported by M. Ligozzi, F. Pittaluga, and R. Fontana, (J. Bacteriol.
      175:2046-2051, 1993) to be a genetic element located just upstream of the
      structural gene for the low-affinity penicillin-binding protein 5 (PBP 5) in the
      chromosome of Enterococcus hirae ATCC 9790 and to be involved in the repression
      of PBP 5 synthesis. By comparing properties of strains of E. hirae that contain a
      full-length, functional psr with those of strains that possess a truncated form
      of the gene, we have obtained data that indicate that psr is involved in the
      regulation of several additional surface-related properties. We observed that
      cells of strains that possessed a truncated psr were more sensitive to lysozyme
      catalyzed protoplast formation, autolyzed more rapidly in 10 mM sodium phosphate
      (pH 6.8), and, in contrast to strains that possess a functional psr, retained
      these characteristics after the cultures entered the stationary growth phase.
      Cellular lytic properties did not correlate with differences in the cellular
      contents of muramidase-1 or muramidase-2, with the levels of PBP 5 produced, or
      with the penicillin susceptibilities of the strains. However, a strong
      correlation was observed with the amounts of rhamnose present in the cell walls
      of the various strains. All of the strains examined that possessed a truncated
      form of psr also possessed approximately one-half of the rhamnose content present
      in the walls of strains that possessed a functional psr. These data suggest that
      psr is also involved in the regulation of the synthesis of, or covalent linkage
      to the cell wall peptidoglycan of, a rhamnose-rich polysaccharide. These
      differences in cell wall composition could be responsible for the observed
      phenotypic differences. However, the multiple effects of psr suggest that it is
      part of a global regulatory system that, perhaps independently, affects several
      cell surface-related properties.

PMID- 8752349
TI  - Rhodobacter capsulatus CycH: a bipartite gene product with pleiotropic effects on
      the biogenesis of structurally different c-type cytochromes.
AB  - While searching for components of the soluble electron carrier (cytochrome c2)
      independent photosynthetic (Ps) growth pathway in Rhodobacter capsulatus, a Ps-
      mutant (FJM13) was isolated from a Ps+ cytochrome c2-strain. This mutant could be
      complemented to Ps+ growth by cycA encoding the soluble cytochrome c2 but was
      unable to produce several c-type cytochromes. Only cytochrome c1 of the
      cytochrome bc1 complex was present in FJM13 cells grown on enriched medium, while
      cells grown on minimal medium contained at various levels all c-type cytochromes,
      including the membrane-bound electron carrier cytochrome cy. Complementation of
      FJM13 by a chromosomal library lacking cycA yielded a DNA fragment which also
      complemented a previously described Ps- mutant, MT113, known to lack all c-type
      cytochromes. Deletion and DNA sequence analyses revealed an open reading frame
      homologous to cycH, involved in cytochrome c biogenesis. The cycH gene product
      (CycH) is predicted to be a bipartite protein with membrane-associated amino
      terminal (CycH1) and periplasmic carboxyl-terminal (CycH2) subdomains. Mutations
      eliminating CyCH drastically decrease the production or all known c-type
      cytochromes. However, mutations truncating only its CycH2 subdomain always
      produce cytochrome c1 and affect the presence of other cytochromes to different
      degrees in a growth medium-dependent manner. Thus, the subdomain CycH1 is
      sufficient for the proper maturation of cytochrome c1 which is the only known c
      type cytochrome anchored to the cytoplasmic membrane by its carboxyl terminus,
      while CycH2 is required for efficient biogenesis of other c-type cytochromes.
      These findings demonstrate that the two subdomains of CycH play different roles
      in the biogenesis of topologically distinct c-type cytochromes and reconcile the
      apparently conflicting data previously obtained for other species.

PMID- 8752350
TI  - Quorum sensing in Vibrio fischeri: evidence that S-adenosylmethionine is the
      amino acid substrate for autoinducer synthesis.
AB  - Synthesis of the autoinducer signal involved in the cell density-dependent
      activation of Vibrio fischeri luminescence is directed by luxI. The autoinducer
      is N-(3-oxohexanoyl)homoserine lactone, and little is known about its synthesis.
      We have measured autoinducer synthesis by amino acid auxotrophs of Escherichia
      coli that contained luxI on a high-copy-number plasmid. Experiments with cell
      suspensions starved for methionine or homoserine show that either methionine or S
      adenosylmethionine but not homoserine or homoserine lactone is required for
      autoinducer synthesis. The S-adenosylmethionine synthesis inhibitor cycloleucine
      blocks methionine-dependent autoinducer synthesis. Thus, it appears that S
      adenosylmethionine rather than methionine is the molecule required for
      autoinducer synthesis. The amount of 15N-labeled methionine incorporated into the
      autoinducer by growing cultures of a homoserine and a methionine auxotroph was
      measured by mass spectrometry. The labeling studies show that even in the
      presence of homoserine, almost all of the autoinducer produced contains the 15N
      label from methionine. Thus, it appears that S-adenosylmethionine serves as the
      amino acid substrate in the luxI-dependent synthesis of the V. fischeri
      autoinducer.

PMID- 8752351
TI  - Cell division gene ftsQ is required for efficient sporulation but not growth and
      viability in Streptomyces coelicolor A3(2).
AB  - We show that the cell division gene ftsQ of Streptomyces coelicolor A3(2) is
      dispensable for growth and viability but is needed during development for the
      efficient conversion of aerial filaments into spores. Combined with our previous
      demonstration that ftsZ of S. coelicolor is not needed for viability, these
      findings suggest that cell division has been largely co-opted for development in
      this filamentous bacterium. This makes S. coelicolor an advantageous system for
      the study of cell division genes.

PMID- 8752352
TI  - Requirement for genes with homology to ABC transport systems for attachment and
      virulence of Agrobacterium tumefaciens.
AB  - Transposon mutants of Agrobacterium tumefaciens which were avirulent and unable
      to attach to plant cells were isolated and described previously. A clone from a
      library of Agrobacterium tumefaciens DNA which was able to complement these
      chromosomal att mutants was identified. Tn3HoHo1 insertions in this clone were
      made and used to replace the wild-type genes in the bacterial chromosome by
      marker exchange. The resulting mutants were avirulent and showed either no or
      very much reduced attachment to carrot suspension culture cells. We sequenced a
      10-kb region of this clone and found a putative operon containing nine open
      reading frames (ORFs) (attA1A2BCDEFGH). The second and third ORFs (attA2 and
      attB) showed homology to genes encoding the membrane-spanning proteins (potB and
      potH; potC and potI) of periplasmic binding protein-dependent (ABC) transport
      systems from gram-negative bacteria. The homology was strongest to proteins
      involved in the transport of spermidine and putrescine. The first and fifth ORFs
      (attA1 and attE) showed homology to the genes encoding ATP-binding proteins of
      these systems including potA, potG, and cysT from Escherichia coli; occP from A.
      tumefaciens; cysA from Synechococcus spp.; and ORF-C from an operon involved in
      the attachment of Campylobacte jejuni. The ability of mutants in these att genes
      to bind to host cells was restored by addition of conditioned medium during
      incubation of the bacteria with host cells.

PMID- 8752354
TI  - Dynamic aspects of colicin N translocation through the Escherichia coli outer
      membrane.
AB  - Colicin N is a bacteriocin that kills sensitive Escherichia coli cells. After
      binding to the cell surface-exposed receptor, a short period exists when a
      significant number of the cell-associated colicin N molecules are sensitive to
      external enzymes. Two colicin N populations are discriminated by proteases: the
      susceptible pool bound to OmpF porin on the cell surface and another population
      corresponding to protease-inaccessible colicin N. During translocation, colicin N
      reaches the periplasmic space and proteolytic cleavage of the colicin occurs only
      when the outer membrane barrier is permeabilized.

PMID- 8752353
TI  - Genetic control of the resistance to phage C1 of Escherichia coli K-12.
AB  - Escherichia coli K-12 lytic phage C1 was earlier isolated in our laboratory. Its
      adsorption is controlled by at least three bacterial genes: dcrA, dcrB, and btuB.
      Our results provide evidence that the dcrA gene located at 60 min on the E. coli
      genetic map is identical to the sdaC gene. This gene product is an inner membrane
      protein recently identified as a putative specific serine transporter. The dcrB
      gene, located at 76.5 min, encodes a 20-kDa processed periplasmic protein, as
      determined by maxicell analysis, and corresponds to a recently determined open
      reading frame with a previously unknown function. The btuB gene product is known
      to be an outer membrane receptor protein responsible for adsorption of BF23 phage
      and vitamin B12 uptake. According to our data the DcrA and DcrB proteins are not
      involved in these processes. However, the DcrA protein probably participates in
      some cell division steps.

PMID- 8752355
TI  - Demonstration of a folded monomeric form of porin PhoE of Escherichia coli in
      vivo.
AB  - The porins in the outer membranes of gram-negative bacteria are trimeric
      proteins. A folded monomeric form of the Escherichia coli porin PhoE, with a
      higher electrophoretic mobility than that of the denatured protein, has recently
      been detected in in vitro folding studies. To investigate the possible biological
      significance of the folded monomer, we attempted to detect this form in vivo.
      After pulse-labeling, folded monomers could be detected by immunoprecipitation.
      Furthermore, folded monomers were detected in a preparation of mutant PhoE
      porins, in which the subunit interactions were weakened by a E-66-->R
      substitution. Together, these results show that the folded monomer is not an in
      vitro folding artifact but an integral part of the native trimer.

PMID- 8752356
TI  - Salmonella typhi contains identical intervening sequences in all seven rrl genes.
AB  - Salmonella typhi Ty2 rrl genes contain intervening sequences (IVSs) in helix-25
      but not in helix-45 on the basis of observed 23S rRNA fragmentation caused by IVS
      excision. We have confirmed this and shown all seven IVSs to be identical by
      isolating genomic DNA fragments containing each of the seven rrl genes from S.
      typhi Ty2 by use of pulsed-field gel electrophoresis; each rrl gene was amplified
      by PCR in the helix-25 and helix-45 regions and cycle sequenced. Thirty
      independent wild-type S. typhi strains, tested by genomic PCR and DraI
      restriction, also have seven rrl genes with helix-25 IVSs and no helix-45 IVSs.
      We propose that IVS homogeneity in S. typhi occurs because gene conversion drives
      IVS sequence maintenance and because adaptation to human hosts results in limited
      clonal diversity.

PMID- 8752357
TI  - Insertional inactivation of the gene for collagen-binding protein has a
      pleiotropic effect on the phenotype of Staphylococcus aureus.
AB  - This report describes phenotypical changes caused by the insertional inactivation
      of the gene for the collagen-binding protein in Staphylococcus aureus PH100.
      Insertional inactivation resulted in reductions in the amount of fibronectin
      binding protein in PH100 and the ability of intact cells to aggregate in the
      presence of fibronectin. However, the capacity of PH100 to adhere to immobilized
      fibronectin remained the same.

PMID- 8752359
TI  - Experimental rejection of a nonadaptive explanation for increased cell size in
      Escherichia coli.
AB  - Populations of Escherichia coli that have been serially propagated for thousands
      of generations in glucose minimal medium show heritable increases in both cell
      size and growth rate. We sought to test the hypothesis that the increased cell
      size of the derived genotypes could be explained solely by their faster growth.
      The regression of cell size on growth rate differed significantly between
      populations having ancestral and derived genotypes, with the latter producing
      larger cells over almost the entire range of growth rates. Thus, the
      physiological coupling between cell size and growth rate has been evolutionarily
      altered.

PMID- 8752358
TI  - A germination-specific spore cortex-lytic enzyme from Bacillus cereus spores:
      cloning and sequencing of the gene and molecular characterization of the enzyme.
AB  - A gene (sleB) encoding a 24-kDa germination-specific spore cortex-lytic enzyme,
      probably an N-acetylmuramyl-L-alanine amidase, was cloned from Bacillus cereus,
      and its nucleotide sequence was determined. It was indicated that the enzyme is
      produced as a 259-residue protein with a signal sequence of 32 residues and is
      present in dormant spores in its active form. Sulfhydryl reagents inactivated the
      enzyme, but mutation of a single cysteine of the protein, Cys-258, to Gly did not
      cause complete inactivation of the enzyme, suggesting that the residue does not
      function as the catalytic center of enzyme.

PMID- 8752360
TI  - History of training programs in allergy and immunology in Florida.

PMID- 8752361
TI  - Allergy and immunology training in Florida. Current and future.

PMID- 8752362
TI  - The history of bone marrow transplantation. Experience at All Children's
      Hospital.

PMID- 8752363
TI  - Treatment of asthma.

PMID- 8752364
TI  - Current treatment of allergic rhinitis and sinusitis.
AB  - Sinusitis is an infectious, inflammatory disease. Aggressive, multifaceted
      treatment is often required for control, with emphasis on anti-inflammatory
      therapy. Medical and surgical treatment is similar in children and adults, but
      more aggressive therapy, particularly surgery, is more controversial in the
      former.

PMID- 8752366
TI  - Stinging insect allergy in Florida.

PMID- 8752365
TI  - Allergic skin diseases.

PMID- 8752367
TI  - The HIV experience in Florida.

PMID- 8752368
TI  - The Florida environment. Important outdoor aeroallergens.

PMID- 8752370
TI  - Food allergy.

PMID- 8752369
TI  - House dust mite allergy in Florida.

PMID- 8752372
TI  - Drugs, alcohol and liability.

PMID- 8752371
TI  - Immunotherapy. When indicated and how it works.

PMID- 8752373
TI  - Set the record straight.

PMID- 8752374
TI  - [Current concepts and implications for future research on Rhodococcus equi].

PMID- 8752375
TI  - [Symbiotic relationship between Orientia tsutsugamushi and vector mites].

PMID- 8752376
TI  - [Molecular structure and toxic action of Clostridium botulinum neurotoxin].

PMID- 8752377
TI  - [Iron uptake mechanisms of pathogenic bacteria].

PMID- 8752378
TI  - [Adaptive responses and signal transduction in bacteria].

PMID- 8752379
TI  - [Strategy to overcome AIDS by cell-mediated immunity].

PMID- 8752380
TI  - [Role of the M protein of Streptococcus pyogenes and its regulation].

PMID- 8752381
TI  - [The 16S-23s rRNA intergenic spacer regions of mycoplasmas].

PMID- 8752382
TI  - [Novel utilization of antibiotics--a finding method of damaged parts in
      bacteria].

PMID- 8752383
TI  - [The role of capsule in staphylococcal infection and immunity].

PMID- 8752384
TI  - [Medical science of AIDS--perspective].

PMID- 8752385
TI  - [An application of the atomic force microscopy technique to observe
      microorganisms].

PMID- 8752386
TI  - [How does Staphylococcus aureus adapt to environmental stresses?].

PMID- 8752387
TI  - [The founders of neurology. Moritz Heinrich Romberg and Hiroshi Kawahara].
AB  - Moritz Heinrich Romberg was born on November 11, 1795 in Meiningen, Thuringen,
      Sachsen (Germany at present). He had completed his medical studies at Berlin. He
      was greatly influenced by Johann Christian Reil at the University of Berlin,
      Johann Peter Frank in Wien, and Christoph Wilhelm Hufeland, the director of das
      Konigliche Poliklinische Institut, Charite Krankenhaus of the University, and
      devoted himself to the study of nervous diseases. Romberg can be looked on as the
      first great neurologist in the modern sense of the word, because he began the
      neurological propaedeutics in Berlin, and published the first systematic book on
      neurology. The year 1995 is the bicentennial anniversary of his birth. Hiroshi
      Kawahara was born at Ohmura, Nagasaki, in 1865. His medical studies were pursued
      at the University of Tokyo under the guidance of Prof. Elwin von Baelz. He was
      the first neurologist in Japan, to give particular attention to the neurological
      diseases. In 1897, Kawahara described two brother cases belonging to a family
      suffering from muscle atrophy, and characterized it as having sex-linked
      recessive inheritance, adult onset, prominent fasciculation of the tongue and
      four limbs, and relatively benign course of illness. The Kawahara's paper on this
      familial disease later known as "bulbo-spinal muscle atrophy" or "Kennedy-Alter
      Sung disease" is the first description in the world. The textbook written by him
      in 1897 is the first publication dealing with a variety of diseases of the
      nervous system in Japan.

PMID- 8752389
TI  - [Regional cerebral blood flow during migraine].
AB  - Previous studies have shown that migraine with aura is associated with the
      reduction of regional cerebral blood flow (rCBF). However, the question of
      whether the reduction of rCBF during migraine aura is caused by cerebral
      vasospasm or is secondary to the neural depression (spreading depression) is
      still disputed. We measured rCBF by high resolution SPECT method during the
      attack of migraine and examined whether the reduction in flow corresponds to the
      cerebral vascular territory. Fourteen patients with migraine with aura (7 men and
      7 women, 34.7 +/- 17.8 years) were studied. In all the patients rCBF was measured
      during the interictal period and in four patients rCBF was measured during the
      aura of migraine. SPECT measurements of rCBF was performed using Tc-99m-PAO (740
      MBq) as a tracer. During the aura of scintillation scotoma in the unilateral
      visual field rCBF was reduced in the opposite occipital, temporal and thalamic
      regions which corresponded clearly to the region of the posterior cerebral
      arterial territory. The reduction of rCBF was by 31 approximately 49% compared
      with the opposite hemisphere. Cerebral spinal fluid lactate level during the
      headache measured in one patient was higher (38 mg/dl) than the interictal period
      (12 mg/dl). Our data indicated that the reduction of rCBF during the aura is
      caused by ischemia probably due to the cerebral vasospasm and is not secondary to
      the neuronal depression. It was also suggested that the primary site of rCBF
      reduction during the visual aura is the occipital association cortex which is
      reported to be responsible for the visual hallucination.

PMID- 8752388
TI  - [The objective and perspective of recording electrical activity from the central
      nervous system].
AB  - In 1929 Hans Bergr successfully recorded electrical activity from the human brain
      using surface scalp electrodes. Since, the EEG has brought significant
      contributions to the fields of clinical neurology and neurophysiology. As a
      clinical diagnostic tool, the EEG has provided information for functional as well
      anatomical (structural) brain disturbances. As a functional diagnosis, the EEG is
      far superior to other functional tests such as PET, SPECT or functional MRI
      because of its excellent temporal resolution representing moment to moment
      changes in the level of consciousness. However, the progress has been hampered
      due to difficulty in quantifying EEG data because of its extreme dynamics and
      variability, which perhaps reflects yet unknown brain functions. This difficulty
      will be overcome by improved quantification methods and statistical measures
      using various computer applications including topographic mapping, power spectrum
      analysis, covariance, correlation or coherence function. Because of its poor
      spacial resolution, the EEG has relinquished its place to CT and MRI scans as an
      anatomical diagnostic tool. The surface recorded electrical activity is greatly
      attenuated and distorted by the time it reaches to the scalp. This is due to the
      inhomogeneous tissues (CSF, dura, skull, scalp) that intervene between the
      recording electrodes and cortical surface. Because the human body or head
      consists of electroconductive media of various geometries, current distortion,
      far-field potentials or paradoxical lateralizations further complicate the
      interpretation of EEG in postulating the location of anatomical generator sources
      from surface recorded EEG. Advanced computer technology is in progress to
      quantify the EEG data by taking into account the factors of conductivity,
      geometry shape and individual head size. This will improve the accuracy of
      localizing current generator sources in relationship to brain anatomy. By solving
      these problems in a methodical fashion, EEG will become the revelation for
      understanding the functional anatomy of brain and will step closer to Berger's
      dream, "EEG is a window of human mental activity".

PMID- 8752390
TI  - [Autonomic nervous activity in migraine].
AB  - The autonomic nervous function in patients with migraine was studied during
      headache free intervals. (I) Hemodynamic test. The following observations were
      made: (1) a decrease in overshoot in Valsalva's maneuver; (2) orthostatic
      hypotension; (3) low levels of plasma norepinephrine; (4) failure in elevation of
      the plasma norepinephrine level after head-up tilting; (5) dilatation of the
      pupils after instillation in the eyes of 1.25% epinephrine; (6) a long recovery
      time in test by bolus injection of l-norepinephrine. These data suggest that
      patients with migraine show sympathetic hypofunction together with denervation
      hypersensitivity of the iris and arteries. (II) Neuropeptides. Blood samples were
      taken after 30 minutes supine rest in a quiet room and the level of substance-P
      (SP), calcitonin gene-related peptide (CGRP), endothelin-1 (ET-1), and human
      atrial natriuretic peptide (hANP) were determined by radioimmunoassay. The level
      of SP, CGRP, and hANP in classic migraineurs during headache-free intervals were
      significantly lower than that of controls. There was no significant difference in
      the level of ET-1 between migraineurs and controls. These data suggest that
      neuropeptides such as SP, CGRP and hANP are closely related to the
      pathophysiology of migraine. (III) L-arginine infusion test. To examine whether
      or not NO is involved in the pathophysiology of migraine, L-arginine, a precursor
      of NO, was administered. The magnitude of blood pressure decrease in migraineurs
      was significantly greater than that of controls. Although plasma levels of CGRP
      decreased significantly in controls following L-arginine infusion, those of CGRP
      did not change in migraine patients. These data suggest that NO and CGRP may be
      involved in pathophysiology in migraine.

PMID- 8752391
TI  - [Tension type headache with special reference to muscle abnormality].
AB  - Muscle contraction headache (tension-type headache; MCH) usually begins when a
      patient is looking down or bending their neck. In the case of MCH patients, EMG
      activity of the posterior neck muscles at a sitting posture is significantly
      higher than the controls when the orbito-meatal line is horizontal or bending
      downward. Comparing with the controls, blood flow of the posterior neck muscle
      decreases sharply when the head is bent downward. Decrease of the muscle blood
      flow continues if the muscle is passively contracted. However, in the case of
      active contraction, blood flow recovers reflexly in 30 seconds. This explains why
      postural muscle contraction is important. When a patient is ordered to bend her
      neck down at the orbitomeatal line 30 degrees from horizontal, patient complains
      of a dull feeling at her posterior neck muscles in 30 seconds. In two minutes
      dull headache appears at the occipital area, soon becoming more intense and
      spreading to the forehead and temporal area. Once she looks up, muscle
      contraction of the neck disappears though she still feels headache. After the
      local anesthesia is applied to the occipital tender point, her headache
      disappears completely. From this experiment, MCH is a referred pain from
      occipital tender point which is the insertion point of occipital neck muscles.
      Patients with poor stability of cervical bone, and relatively heavy head weight
      compared with their neck are susceptible to MCH. Psychological stress decreases
      blood flow of the muscle and aggravates ischemic muscle contraction. Other risk
      factors include hypotension, anemia, and weak muscle power.

PMID- 8752392
TI  - [Tension-type headache: 5-hydroxytryptamine and related substances].
AB  - There are many reports concerning platelet dysfunction and abnormalities of
      platelet 5-hydroxytryptamine (5-HT) in migrainous patients. In recent years,
      platelets are considered good models of monoamine neurons. Levels of
      neurotransmitters in platelets are suggested to reflect those in the nervous
      system. We reported alteration of platelet neurotransmitters and other biogenic
      substances in migraine and tension-type headache. In patients with tension-type
      headache, the concentrations of platelet 5-HT and norepinephrine were
      significantly lower than in the controls. However, the activity of platelet
      superoxide dismutase was normal in the patients with tension-type headache, while
      the activity of platelet superoxide dismutase in the patients with migraine was
      lower than the controls. A recent study has shown that migraine is associated
      with a generalized disorder of mitochondrial oxidative phosphorylation and this
      may constitute a threshold for the triggering of migraine attacks. Some patients
      with migraine had a mutation in mitochondrial gene. None of the patients with
      tension-type headache had the mutation. the point mutation in the mitochondrial
      gene of these patients may play an important role in the pathogenesis of their
      migraine attacks.

PMID- 8752393
TI  - [Functional MRI of the brain].
AB  - An introduction to functional MRI (fMRI) of the brain was described. Basically
      there are two methods in fMRI; one is using extrinsic substance and the other
      intrinsic substance. The blood oxygen level dependent contrast method, which uses
      intrinsic substance, is used commonly at present. This method is based on the
      idea that the signal intensity changes due to the oxygenation of hemoglobin (Hb)
      in the blood vessels. Oxy-Hb has a diamagnetic property which does not affect the
      signal intensity of water proton. On the other hand, deoxy-Hb is paramagnetic and
      shortens the T2 relaxation time of the water proton. By the activation of brain,
      blood flow increases around the activated area with a little increase of oxygen
      consumption, resulting in an increase of oxy-Hb in the capillary of this area.
      Consequently signal increase occurs in the activated area of the brain on MRI due
      to the decrease of deoxy-Hb. The fMRI was measured by pulse sequences sensitive
      to the T2 changes such as echo planar imaging (EPI) on 1.5 T systems or gradient
      echo imaging (GRE) on high-filed magnetic systems (3.0-4.0 T). It becomes
      possible to get fMRI on conventional MRI scanners using GRE pulse sequence. Many
      activation tasks are adopted for fMRI; not only simple tasks such as motor,
      photic and sensory stimulations but also complex tasks such as hearing of words,
      word generation, imagination, coordination motion, etc. A rapid increase of
      signal intensity was observed in the primary cortical area corresponding to each
      task, and the activated area is visualized by the subtraction imaging or
      statistically treated imaging. The fMRI has big advantages to get brain
      functional imaging because of non-invasive measurement, using intrinsic
      substance, highly spatial and temporal resolution and easy measurement on
      conventional clinical devices. Therefore, the fMRI will be used more and more
      widely in future, especially by introducing the EPI technique to the clinical MRI
      scanners.

PMID- 8752395
TI  - [Surgery for intractable epilepsy--selection and presurgical evaluation].
AB  - Success in epilepsy surgery depends upon the exact localization of epileptogenic
      lesion identified by recordings of scalp and/or intracranial EEG and observation
      of clinical seizures in addition to the neuroimaging techniques such as CT, MRI,
      SPECT, PET. Thinking of the postoperative outcome in the literatures regarding
      epileptic seizures according to surgical procedure, main candidates for surgery
      are patients with intractable symptomatic localization-related epilepsies.
      Walker's criteria (1974) are generally agreed as selection criteria of candidate
      for epilepsy surgery. In our hospital, candidates for temporal lobe resection are
      selected according to the following criteria: 1) presence of an epileptogenic
      region presumably within the temporal lobe, 2) appropriate drug treatment for at
      least 5 years, 3) complex partial seizures more frequently than once a week, 4)
      adolescent or adult patients over 15 years of age with no persistent psychiatric
      symptoms, and 5) patients capable of social rehabilitation if recurrent seizures
      subside. Presurgical evaluation consists of noninvasive and invasive evaluation.
      Noninvasive evaluation includes neuro-psychological tests including Wada test,
      neuroimagings, interictal and ictal long-term intensive EEG/CCTV monitoring by
      the scalp EEG using 10/20 electrode placement as well as sphenoidal electrode to
      catch at least 3 spontaneous seizures. Invasive evaluation is interictal and
      ictal long-term intensive EEG/CCTV monitoring by intracranial electrodes for two
      weeks. The presurgical evaluation is performed by the team composed of
      neurosurgeon, neurologist, neuropsychiatrist, and neuropediatrician to decide the
      localization of epileptogenic lesions for resection. Outcome concerning seizure,
      neuropsychological aspects, and QOL is followed for more than 3 years after
      operation. Surgery for epilepsy should not be done without strict presurgical
      evaluation.

PMID- 8752394
TI  - [Diagnosis and clinical assessment of abnormal eye movements].
AB  - Abnormal eye movements and nystagmus are, when present, useful for diagnosis of
      localization of the lesion. Observations of mortality and range of eye movements,
      pursuit and saccadic eye movements, ability of visual fixation, nystagmus and
      involuntary eye movements as well as head and eye position, palpebral fissures,
      ptosis, pupils are important for assessment of eye movements. Anatomical pathways
      important for horizontal eye movements locate in the caudal pons and for vertical
      eye movements, in the rostral mesencephalon. In those structures two types of
      saccade related neurons--burst cells and pause cells-are present and generate
      premotor saccadic commands. The gaze directed nystagmus results from the central
      vestibular disorder, not from the peripheral labyrinthine lesion. Bruns'
      nystagmus characterized by low-frequency, large amplitude nystagmus on looking
      ipsilaterally and high-frequency, small-amplitude nystagmus on looking
      contralaterally, is seen in the brainstem lesion. Ocular bobbing consists of
      rapid downward movement of the eyes followed by a slower return to the primary
      position and is a sign of pontine lesion. Opsoclonus, multidirectional saccadic
      oscillation with out intersaccadic interval and flatter-like oscillation, purely
      horizontal saccadic oscillation are seen in patients with cerebellar and
      brainstem lesions and may be due to dysfunction of pause cells.

PMID- 8752396
TI  - [A clinicopathological study of the Guillain-Barre syndrome--fifteen Japanese
      postmortem cases].
AB  - The postmortem findings of the ventral roots and ventral horn cells of 15
      Japanese cases of Guillain-Barre syndrome are reported. In 5 cases there was
      predominant axonal involvement with severe axon loss in the lumber ventral root.
      Eight cases showed predominantly segmental demyelination, and two cases were the
      intermediate form with both segmental and axonal changes. Macrophage invasion in
      the ventral roots predominantly occurred in the cases with axonal involvement.
      Large-sized motor neuron loss and reactive astrogliosis were also seen in the
      cases with axonal degeneration. These findings indicate that approximately 30% of
      Japanese autopsied cases were "axonal form", the incidence of which was higher
      than that reported in European and North American countries, but was lower than
      that in Chinese endemic acute motor axonal neuropathy.

PMID- 8752397
TI  - [Electrodiagnostic features in inflammatory demyelinating polyneuropathy].
AB  - Demyelinating conduction block is an important hallmark to distinguish chronic
      inflammatory demyelinating polyneuropathy (CIDP) from hereditary neuropathies,
      motor neuron disease and other axonal type neuropathies. The electrodiagnostic
      criteria of partial conduction block proposed by Asbury and Cornblath, more than
      20% drop in CMAP amplitude between proximal and distal sites (e.g. elbow and
      wrist), may be inadequate, because 20% to 30% drop sometimes occurs in cases with
      hereditary demyelinating neuropathies. Rhee et al showed that pure temporal
      dispersion can produce amplitude reduction up to 50% without conduction block.
      This reduction between elbow and wrist is equivalent to 2% drop/cm. Since lesions
      are multifocal in CIDP, more than 2% drop/cm in relatively short segments could
      be a convincing finding of conduction block of CIDP or multifocal motor
      neuropathy. Our inching study has revealed that chance of lesion is equal from
      distal to proximal along the nerves of CIDP. However, it is not true in AIDP;
      most distal sites, roots, and physiological entrapment sites are more fragile,
      and early demyelination and secondary axonal degeneration start there. Axonal
      degeneration easily makes demyelinating conduction changes; therefore, in
      diagnosis of axonal form of AIDP, the possibility of early Wallerian degeneration
      has to be ruled out by careful follow-up, and delayed F-wave or long-latency
      units definitely go against the primary axonal pathology.

PMID- 8752398
TI  - [Potassium channel dysfunction at the lesion site in multifocal motor neuropathy
      as revealed by threshold electrotonus].
AB  - Multifocal motor neuropathy presents as a treatable muscular atrophy and is
      characterized by persistent conduction block and fasciculations or myokymia.
      Although the pathological findings at the lesion site revealed perivascular
      demyelination with little evidence of remyelination, the mechanism of conduction
      block is still unknown. We explored the threshold electrotonus, which registers
      membrane potential changes through threshold variation, at the lesion site. The
      findings were consistent with focal potassium channel dysfunction, with some
      evidence of depolarization block. The disrupted blood-nerve barrier and lack of
      Schwann cell-mediated extracellular potassium regulation may predispose the
      membrane depolarization, thereby accounting for the conduction block and
      fasciculations. Sensory nerve fibers are known to have more inward rectifiers,
      which take up the extracellular potassium, than motor fibers, and this may
      explain the sparing of these fibers.

PMID- 8752399
TI  - [Antiglycolipid antibody in inflammatory neuropathy].
AB  - Antiglycolipid antibody is frequently detected in the acute phase sera from
      patients with acute inflammatory demyelinating polyneuropathy (Guillain-Barre
      syndrome, GBS). The titer is highest in the serum sample taken first after the
      neurological onset, and decreases with clinical improvement. Antiglycolipid
      antibody may play a role in the pathogenetic mechanism of GBS. GM1 and GD1b are
      the antigens most commonly recognized. Monoclonal anti-GD1b antibody specifically
      bound to the paranodal myelin of the peripheral nervous system. Serum anti-GD1b
      antibody may cause demyelinative neuropathy by binding to the paranodal myelin of
      the peripheral nervous system. Anti-GQ1b IgG antibody is specifically raised in
      almost all the sera from Fisher syndrome and GBS with ophthalmoplegia. Anti-GQ1b
      monoclonal antibody immunostained specifically the paranodal myelin of the
      extramedullary portion of oculomotor, trochlear and abducens nerves, but no such
      staining was observed in the other peripheral nerves. Anti-GQ1b antibody may
      cause conduction block in the cranial nerves innervating the muscles for
      extraocular movement by binding to the paranodal myelin of those nerves. Anti
      GalNAc-GD1a antibody is detected in the patients with GBS with very low or
      inexcitable compound muscle action potentials. The sera from patients with GBS
      subsequent to mycoplasma infection had antigalactocerebroside antibody. Further
      study on antiglycolipid antibody is needed for understanding the pathogenetic
      mechanism of GBS.

PMID- 8752401
TI  - [Anti-ganglioside antibodies in CIDP and related disorders].

PMID- 8752400
TI  - [Pathogenesis of Guillain-Barre syndrome and Fisher's syndrome: molecular mimicry
      between antecedent infectious agents and components of nerve tissues].
AB  - Sera from patients with Guillain-Barre syndrome (GBS) following Campylobacter
      jejuni infection have autoantibody to GM1 ganglioside. We have investigated
      whether GM1-oligosaccharide structure is present in the lipopolysaccharide (LPS)
      of C. jejuni (PEN 19) that was isolated from a GBS patient. The LPS showing the
      binding activity of cholera toxin, which specifically recognizes the GM1
      oligosaccharide, was purified by a column chromatography. Proton NMR methods have
      revealed that the LPS has the oligosaccharide structure [Gal beta 1-3GalNAc beta
      1-4 (NeuAc alpha 2-3) Gal beta 1-], which is identical to the terminal
      tetrasaccharide of GM1 ganglioside. Fisher's syndrome (FS) is very frequently
      associated with anti-GQ1b ganglioside antibody. We isolated C. jejuni from 2
      patients with FS subsequent to enteritis. Crude LPS fractions were extracted from
      the bacteria and separated by thin-layer chromatography. Monoclonal antibodies to
      GQ1b ganglioside (GMR 13 and 7F5) reacted with both LPS fractions, indicating
      that the LPSs bear GQ1b epitope. These findings strongly support that "molecular
      mimicry" between infectious agents and components of nervous system function in
      the development of post-infection disorders.

PMID- 8752403
TI  - [Guillain-Barre syndrome and infection].

PMID- 8752402
TI  - [The effect of anti-GM1 antibodies on ionic channel in myelinated nerve].

PMID- 8752405
TI  - [Pathophysiology of involuntary movements--dystonia and myoclonus from viewpoint
      of brain activities].
AB  - Cortical myoclonus (CM) and focal dystonia (FD) are commonly characterized by co
      contraction of agonist and antagonist muscles, enhancement by intentional
      movement, strong influence by sensory input, and spread to adjacent muscles. On
      the other hand, they are different in the nature of movements, speed of muscle
      contraction, speed of spread, and drug effects. There are abundant data
      indicating that CM is due to pathological hyperexcitability of the sensorimotor
      cortex (S1-M1), while, in FD, no definitive evidence to suggest cortical
      hyperexcitability has been found. Changes in regional cerebral blood flow (rCBF)
      studied by positron emission tomography (PET) during movements in patients with
      dystonia were inconsistent with regard to S1-M1, but the frontal cortex including
      the rostral SMA was shown to be overactivated, suggesting the thalamocortical
      disinhibition based on the basal ganglia disorders.

PMID- 8752404
TI  - [Pathophysiology of involuntary movements--dystonia and myoclonus.
      Symptomatological view].
AB  - Among involuntary movements, dystonia is defined as abnormal posturing produced
      by slow sustained muscle contractions. On the contrary, myoclonus is
      characterized by sudden shock-like contractions of a muscle or a group of
      muscles. The electromyogram (EMG) in dystonia shows continuous activity lasting 5
      seconds or more. The muscles usually co-contract in the antagonists. In myoclonus
      the muscle bursts on EMG last usually between 10 and 50 ms. In some cases the
      bursts last longer, but they are 200 ms at most. Thus, the characteristics of
      myoclonus is quite different from those of dystonia. There are, however, unusual
      combination of dystonia and myoclonus. Myoclonic dystonia, in which myoclonic
      jerks are so severe that crucial dystonic posturing may be ignored, has been
      reported. Essential tremor, writing tremor and writer's cramp (writing dystonia)
      and myoclonic writer's cramp are sometimes seen in one family in various
      combination. It is suggested that there may be pathophysiological relationship
      between dystonia and myoclonus, although these two movement disorders have
      different clinical characteristics.

PMID- 8752406
TI  - [Electromyographic analysis of cortical myoclonus and focal dystonia].
AB  - We have done a few physiological studies on six patients with cortical reflex
      myoclonus and three patients with unilateral focal dystonia caused by a discrete
      cerebrovascular lesion in the basal ganglia. The silent period after magnetic
      cortical stimulation was normal or slightly prolonged in all the patients with
      cortical myoclonus. In contrast, in patients with focal dystonia, it was
      shortened in the muscles on the contralateral side to the lesion, whereas normal
      in duration on the ipsilateral side. Excessive inputs from the disinhibited
      supplementary motor cortex to the primary motor cortex due to a lesion of the
      basal ganglia must cause this shortening in the dystonic hand muscles.
      Excitability recovery of the motor cortex after hypersynchronous activation by
      magnetic stimulation should be prolonged in the myoclonic patients. Cortico
      cortical inhibition of the motor cortex studied with paired magnetic stimulation
      technique was disturbed in both the patients with myoclonus and those with
      dystonia. This result suggested that the disinhibition of the motor cortex is
      present in both disorders. Based on these results, we conclude that the motor
      cortex is similarly disinhibited in both disorders, but recovery function from
      hypersynchronous activation is different between these two groups.

PMID- 8752407
TI  - [Pathophysiologies of dystonia and myoclonus--consideration from the standpoint
      of treatment].
AB  - Pathophysiologies of disorders with dystonia or myoclonus were studied by
      evaluating the effects of treatment. Naturally, the main lesion of the dystonia
      responding to levodopa is in the nigrostriatal dopamine neuron. The target of
      stereotaxic operations is ventrolateral palladium for postural dystonia and the
      nucleus ventralis oralis posterior (Vop) thalamus for action dystonia. Torsion
      dystonia with lesion in the striatum and/or the pallidum causes axial torsion, it
      may be postural through the descending pathway and action through Vop.
      Stereotaxic operations on these pathways have shown to be effective. Focal
      dystonia is a reflection of abnormal co-activation of cortical motor neurons,
      occurring in a particular voluntary movement. Botulinus toxin injected into the
      affected muscle should be effective. Of myoclonus with epilepsy, cortical reflex
      myoclonus or cortical induced reticular myoclonus responds to valproic acid.
      However, no antiepileptic drugs are effective on those with primary brainstem
      lesion. Reticular reflex myoclonus due to asphyxia responds to ventralis
      intermedius thalamotomy. Idiopathic myoclonus associated with dystonia is
      particular because it responds to ventrolateral thalamotomy. Myoclonus except for
      idiopathic myoclonus with dystonia is associated with atonic NREM suggesting
      dysfunction of the dorsal raphe serotonergic neuron or the brainstem nucleus
      reticularis gigantocellularis, the causative neuron for experimental uremic
      myoclonus. Treatment for these neurons is necessary.

PMID- 8752408
TI  - [Epidemiology of syringomyelia in Japan--the nationwide survey].
AB  - The nationwide epidemiological survey of syringomyelia was carried out in Japan
      by sending inquiries to neurologists, child neurologists, neurosurgeons and
      orthopedic surgeons for the period of 1991 and 1992. A total of 1,243 cases of
      syringomyelia were ascertained. Among them, 622 were men and 619 women, and the
      average age of onset was 28 years old. The classification by Barnett et al was
      used, presenting syringomyelia with Chiari malformation in 684 cases (51.2%),
      dysraphism in 47 (3.7%), post traumatic syringomyelia in 139 (11%), post-spinal
      arachnoiditis in 76 (6%), spinal cord tumor in 132 (10.5%) and others in 204. Its
      predominant clinical course was slowly progressive, but 202 cases (17.9%) showed
      rather stable course including spontaneous resolution in 29 cases. The main
      initial symptoms were numbness in 522 cases (42%), motor disturbance in 504
      (40.5%), and pain in 296 (23.8%). Neurologic signs noted in the abnormality of
      deep tendon reflexes in 836 cases (67.3%), motor disturbance in 763 (60.4%) and
      positive pathological reflexes in 383 (30.1%). Sensory disturbance was found in
      942 cases (75.8%) and the dissociated type were 559 out of them (59.3%). It is
      noteworthy that 982 out of 1,243 were documented by MRI and surgical operations
      such as foramen magnum decompression, syringo-subarachnoid shunt and others were
      performed in 829 cases. Syringobulbia was confirmed on MRI in 101 cases of
      syringomyelia in which spinal cord tumors were most frequently associated.

PMID- 8752409
TI  - [Hydrodynamics of syringomyelia].
AB  - Abnormality of CSF hydrodynamics is an important factor of the pathogenesis of
      syringomyelia. Recent development of cine-MRI visualized real time CSF movement
      in the syrinx or subarachnoid space. In the present study, twenty cases of
      syringomyelia associated with Chiari I malformation, 10 cases of syringomyelia
      associated with spina bifida aperta, and 10 cases of syringomyelia associated
      with spina bifida occulta were studied with MRI and cine-MRI. The result
      demonstrated that hydrodynamics of these three groups were different to each
      other. Chiari I malformation showed CSF hydrodynamic abnormality at the foramen
      magnum and marked flow void in the syrinx. On the other hand, myelomeningocele
      showed hydrocephalus and less prominent flow void in the syrinx. Spinal lipoma
      which is the majority of spina bifida occulta showed no abnormality of CSF
      hydrodynamics. In conclusion, the selection of treatments should be
      individualized depending on the hydrodynamical abnormality of each patient.

PMID- 8752410
TI  - [Neuropathology of syringomyelia].
AB  - Eighteen autopsy cases of syringomyelia were studied neuropathologically. In 5
      cases associated with Chiari type I malformation, the syrinx was irregular in
      shape and communicated with the subarachnoid space at the entry zone of the
      posterior nerve roots. The central canal above the level of the syrinx was patent
      in 2 but closed in 3 out of 5 cases. In cases associated with Chiari type I
      malformation, communication between the syrinx and the subarachnoid space was
      considered to play an important role in the pathogenesis of syringomyelia. In 6
      cases associated with Chiari type II malformation, the syrinx central canal, and
      the central canal was patent from the 4th ventricle to the syrinx in all cases.
      In these cases, direct continuity between the 4th ventricle and the syrinx was
      essential for the development of the syrinx. In cases associated with posterior
      fossa or spinal canal tumors, the local circulatory disturbance and/or edema due
      to the tumors were thought to cause the syrinx.

PMID- 8752411
TI  - [Neurological manifestations of syringomyelia].
AB  - The subjects were among the patients registered at the Nagoya University
      Hospital, Aichi Medical University Hospital and Nagoya National Hospital between
      1972 and 1995. There were 21 males and 21 females in this series. Symptoms began
      at 10 to 55 years of age. Cranial nerves were involved in 57% of the cases. The
      bulbar lesion was usually unilateral and on the same side as the cervical lesion.
      In regard to the cardinal signs of syringomyelia, segmental dissociated sensory
      loss was present in 95% of cases, segmental atrophy of upper limbs in 90%, and
      loss of sweating in 48%. Advanced cases became chair-bound because of spastic
      paralysis. However, they usually had no bulbar palsy nor sphincter disturbances,
      and the life expectancy was close to normal with adequate nursing. In twenty-one
      cases undergoing operation of posterior fossa decompression, the side of greater
      tonsilar herniation corresponded to the dominant side of cervical lesion.

PMID- 8752412
TI  - [Surgical treatment of syringomyelia].
AB  - Eighty cases of surgically treated syringomyelia were retrospectively reviewed.
      The cases were classified into following 4 types, type 1: syringomyelia with
      Chiari malformation (54 cases), type 2: syringomyelia with basal arachnoiditis
      (15 cases), type 3: syringomyelia with an obstruction of the foramen Magendie (1
      case), and type 4: syringomyelia with spinal arachnoiditis (14 cases). Foramen
      magnum decompression (FMD) was performed in patients with type 1, in type 2
      fourth ventricle-subarachnoid shunt was additionally performed. Gardner's
      operation was performed in patients with type 3. Syrinx-peritoneal shunt was
      performed in patients with type 4. Surgical procedures for syringomyelia which we
      selected were thought to be appropriate, based on postoperative syrinx collapse
      rate in MRI. However, postoperative clinical course was much different in each
      type of syringomyelia after the collapse of syrinx had been equally achieved.
      Neurological disorders were stopped in deterioration after surgery in all cases
      of type 1. However, motor weakness was still deteriorated in half cases of type
      2, and in 60% of type 4. When clinical severity of the patients with type 1 and
      2, based on the distribution of dissociated sensory loss and motor weakness, were
      classified into 5 grades. The rate of improvement of patient's symptoms and signs
      was higher in the lower grades. We concluded that a surgical treatment for
      syringomyelia was essentially a preventive one, therefore it should be done in
      early stage of disorders.

PMID- 8752413
TI  - [Surgical treatment for syringomyelia associated with Chiari malformation].
AB  - Two major surgical procedures, i.e., foramen magnum decompression (FMD) and
      syringo-subarachnoid shunt (S-S shunt) have been performed as the treatment for
      syringomyelia with Chiari malformation in our department. FMD was done
      principally in patients with symptoms due to Chiari malformation and for small
      size or localized syrinx, and S-S shunt was applied to patients with main
      symptoms due to syringomyelia, especially with local pain and for large syrinx in
      size. Eighty patients of syringomyelia with Chiari malformation were surgically
      treated. FMD was performed in 38 patients, and S-S shunt in 39 patients as the
      first operation. FMD were done with craniectomy of posterior fossa, C1
      laminectomy and resection of epidural band, but without opening dura, and S-S
      shunt were done with hemipartial laminectomy and DREZtomy. The clinical outcome
      was evaluated, comparing the two major surgical procedures. Satisfactory
      neurological improvement was obtained in the two groups, but S-S shunt group took
      better improvement than FMD group. These results suggest that both procedures are
      effective, but should be selected by preoperative clinical and radiological
      findings.

PMID- 8752414
TI  - [Problems found in genetic diagnosis of DMD/BMD].
AB  - The method to understand the result of the multiplex PCR amplification of the
      dystrophin gene has been discussed. In dystrophin Kobe, a very small intra-exon
      deletion was identified in exon 19 when the amplified product was not detected in
      its corresponding position. Also, an insertion mutation was identified in exon 44
      of the dystrophin gene named dystrophin Yakumo. In this case the amplified
      product from exon 44 was not localized to the its expected position, but a larger
      fragment was identified. In one case of BMD all exons were amplified by multiplex
      PCR. However, thorough examination disclosed the presence of point mutation at
      the last nucleotide of exon 13.

PMID- 8752415
TI  - [Genetic analysis of facioscapulohumeral muscular dystrophy (FSHD)].
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscular
      disorder which is characterized by progressive weakness and atrophy of the
      facial, shoulder-girdle and upper arm muscles, and occasional subsequent pelvic
      girdle and lower limb involvement. The gene responsible for FSHD has been
      localized to chromosome 4q35-qter, although a few 4q-unlinked families are known.
      To examine FSHD-associated DNA rearrangements in the Japanese population, we
      performed Southern blot analysis of the genomic DNA, using the p13E-11 and pFR-1
      probes. Most of the Japanese FSHD patients (> 95%) had specific smaller (< 28 kb)
      EcoRI fragments which cosegregated with the disease. Restriction enzyme maps of
      the polymorphic EcoRI fragment detected by the probes have revealed that the
      disease occurs due to a deletion of the integral numbers of the 3.3kb KpnI
      tandemly repeated fragments (D4Z4) which contain homeobox-like sequences. Indeed,
      we cloned and characterized the FSHD-associated EcoRI fragments (the shortest
      fragment identified to date: 10kb) from two severely affected patients
      (unrelated). The 10kb fragment were identical and contained only one 3.3kb KpnI
      repeat unit. Although we still do not know whether truncation deletion of the
      D4Z4 region could produce FSHD directly or indirectly (position effect), we now
      beginning to understand FSHD. In the next step, FSHD gene products (mRNA and
      protein) responsible for the disease should be investigated.

PMID- 8752416
TI  - [Recent progress, genetic diagnosis and its problem on congenital muscular
      dystrophies (Fukuyama and non-Fukuyama types)].
AB  - Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive
      muscular dystrophy associated with an anomaly of the brain. We performed genetic
      linkage analyses using consanguineous FCMD families and localized the FCMD locus
      to chromosomes 9q31-33. We further defined the locus within a region of 5 cM and
      also found strong linkage disequilibrium between FCMD and mfd220. We suspect that
      the FCMD gene could lie within one megabases of the mfd220 locus located on 9q31.
      This achievement made prenatal and carrier diagnosis in families carrying FCMD
      feasible. However, in principle, it is impossible to diagnose whether a patient
      has FCMD or not, since this is an indirect genetic diagnosis by polymorphisms
      analysis. It has been discussed whether FCMD and Walker-Warburg syndrome (WWS)
      belong to the same disease entity or not. We analyzed a family in which 3
      siblings were affected with either FCMD or WWS. The results suggested that both
      FCMD and WWS siblings shared the identical combination of mutations on either
      allele of the FCMD locus. Some WWS cases could be caused by mutations in the FCMD
      gene. A novel clinical entity of merosin-negative CMD was proposed out of
      classical, non-Fukuyama CMD cases. This condition mapped to 6q2, the merosin gene
      region. CMD researches are in rapid progress.

PMID- 8752417
TI  - [Severe childhood autosomal recessive muscular dystrophy].
AB  - Dystrophin is associated with several novel sarcolemmal proteins via the cysteine
      rich/C-terminal domains. The dystrophin-associated proteins are classified into
      three groups: (1) alpha- and beta-dystroglycan, (2) adhalin, 35DAG and A3b, and
      (3) members of the syntrophin family. Dystrophin interacts with F-actin via the N
      terminal domain. Alpha-dystroglycan binds laminin-2, a major component of the
      basal lamina. These findings indicate that the dystrophin-glycoprotein complex
      (DGC) links the subsarcolemmal cytoskeleton with the basal lamina, thus providing
      mechanical stability to the sarcolemmal. The DGC may also play a role in signal
      transduction. We have reported previously the deficiency of adhalin in skeletal
      muscle of Arab patients afflicted with severe childhood autosomal recessive
      muscular dystrophy (SCARMD). SCARMD is now known to affect other races including
      Europeans and Japanese. Although the phenotype of this disease can mimic Duchenne
      muscular dystrophy in severe cases, it is sometimes quite mild. SCARMD is
      genetically heterogeneous. Recently, adhalin gene mutations have been
      demonstrated in European, Arab and Japanese families with SCARMD. Another locus
      is on chromosome 13q, however, the mutated gene remains elusive. In the advanced
      stages of SCARMD, the expression of laminin is disturbed, suggesting that adhalin
      deficiency may cause the dysfunction of the DGC as a laminin receptor, which may
      eventually lead to muscle cell death.

PMID- 8752418
TI  - [Mitochondrial encephalomyopathies: 3243 mutation as a central matter].
AB  - Molecular diagnosis for mitochondrial diseases offers a powerful means to clarify
      that mitochondrial DNA (mtDNA) defects have different characteristics from those
      of nuclear DNA. Regarding the relationship between genotype and phenotype, there
      is a dual heterogeneity. It means that one mutation, for example, a 3243
      mutation, has several clinical phenotypes, including MELAS (mitochondrial
      myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), myopathy
      only, diabetes and/or deafness and even CPEO (chronic progressive external
      ophthalmoplegia). Conversely, one phenotype, for instance, MELAS has several
      genetypes; 3243, 3271, and 3291 mutations. The second unique event in
      mitochondrial DNA mutation is heterogenous distribution of mutant mtDNA in a
      mitochondrion or a cell that is called heteroplasmy. The extend of heteroplasmy
      seems different from tissue to tissue providing clues to explain the variability
      of tissue impairment and heterogenous clinical symptoms. The above evidence
      suggests that we should take care in selecting tissues to be tested. The third
      problem remained is on maternal inheritance. It makes the genetic counselling on
      mitochondrial diseases at clinics difficult and laborious. In conclusion, mtDNA
      analysis must be used as a last resort to get final diagnosis.

PMID- 8752419
TI  - [Psycho-social effects of DNA diagnosis].
AB  - (1) A VIEWPOINT OF PATIENTS/FAMILIES WITH MUSCULAR DYSTROPHY (MD). The results of
      questionnaire survey about DNA diagnosis in the members of JMDA, performed in
      1992, were as following: The rate having a knowledge of DNA diagnosis (ca one
      third) did not differ between in patients and families, but more families accept
      DNA diagnosis, especially prenatal examinations, than patients. (2) AN ATTITUDE
      OF DOCTORS TOWARD DNA DIAGNOSIS OF MD. Eighty percent of doctors having answered
      a questionnaire were of the opinion that DNA examinations in MD should be met by
      health insurance coverage. Genetic counselors work in just 24% of the
      institutions. Most doctors' consultation seems still content-oriented than person
      oriented. (3) PRESENT PROBLEMS. Informed-choice and DNA privacy should be
      respected more. Nonofficial laboratories are keeping DNA materials of patients.
      They impose voluntary but not legal controls upon themselves. Official quality
      control for DNA examinations also will be required. (4) THE FUTURE PROSPECTS. One
      of the resolutions of present ethical and economical issues is establishing DNA
      Medicine Foundation for MD with a DNA Bank, which will be conducted medical staff
      and patient/family group under the support of the Ministry of Health.

PMID- 8752420
TI  - [Familial amyloidotic polyneuropathy (FAP) type I and the therapies].
AB  - Since autonomic dysfunction in familial amyloidotic polyneuropathy (FAP) Type I
      is recognized in the early stage of FAP patients and restricts their daily life,
      we developed various therapies for various autonomic manifestations: Loading
      glucose was often effective for faintness caused by hypoglycemia and
      erythropoietin was also good therapy for orthostatic hypotension as well as
      anemia found in the end stage of FAP patients. Stoma and nasal drop of L-threo
      DOPS were useful to control diarrhea and orthostatic hypotension. Duplex
      ultrasonography of the 4 vessels revealed that reverse flow was always recognized
      in FAP patients with faintness, which was effectively treated by the
      administration of L-threo-DOPS. Orthotopic liver transplantation revealed
      effective therapy for autonomic dysfunction in FAP patients. Precise analysis of
      protein metabolism in FAP patients revealed that among apolipoproteins, only
      apolipoprotein AII decreased as the progression of the disease and high density
      lipoprotein gained the negative charge by agarose electrophoresis study.
      Concerning low density lipoprotein (LDL) study, only variant transthyretin in the
      circulation associated with LDL in FAP patients, suggesting that LDL may play an
      important role in the amyloid formation of FAP.

PMID- 8752421
TI  - [Variable clinical manifestations of familial amyloid polyneuropathy and living
      related liver transplantation].
AB  - Familial amyloid polyneuropathy (FAP) is clinically characterized by
      polyneuropathy and autonomic failure but it shows diverse clinical pictures in
      different families. We presented clinical and molecular biological findings for a
      peculiar family in which type I FAP and spinocerebellar ataxia type 1 (SCA-1)
      coexist. Type IV FAP which is also called familial amyloidosis, Finnish type
      (FAF), shows the triad of corneal lattice dystrophy, cranial neuropathy and
      various skin changes. Recently, 3 FAF families were reported in our country, and
      their clinical pictures and gene abnormalities closely resembled those seen in
      Finnish patients with this disease. FAP had long been considered to be a
      genetically determined incurable disorder. Since it has been shown that the
      precursors of amyloid fibrils (variant forms of transthyretin) in this disorder
      are produced mainly in the liver, successful results of liver transplantation
      (LT) were reported in several countries. In our country there are many FAP
      patients, but LT from a cadaveric donor is still not possible. We, therefore,
      performed a partial LT for 3 FAP patients using a graft taken from healthy family
      members, resulting in good outcomes. It seems likely that this partial LT is a
      very promising therapeutic approach for FAP patients.

PMID- 8752422
TI  - [Protein and DNA sequencing analyses of transthyretin in familial amyloidotic
      polyneuropathy].
AB  - Recent advances in protein chemistry and the molecular biology of amyloid
      proteins have led to knowledge of the primary etiology of FAP. The protein
      product of the gene in question was identified, then the chromosomal location and
      point mutations in the gene were determined. Diagnosis of the disorder now can be
      made at the protein and DNA levels. Recombinant techniques for producing variant
      proteins have been established and a transgenic mouse that carries the mutated
      gene have been produced. Liver transplantation, a curative therapy for FAP, has
      been used for some patients. Procedures for the diagnosis of TTR-related FAP and
      the elucidation of TTR abnormality are summarized as follows: TTR-related FAP
      should be considered when biopsies of abdominal fat, the gingiva, stomach, rectum
      and sural nerves demonstrate amyloid deposits that are specifically stained by
      anti-TTR antiserum. Analysis of the TTR gene based on RFLP and single strand
      conformational polymorphism is useful for detecting the genetic mutations
      identified so far. Even when no known mutations have been detected, protein
      sequence analysis of serum TTR and nucleotide sequence analysis of the TTR gene
      have shown new variant TTRs. These advances in FAP research herald a new era in
      our investigation of the molecular biology of inherited neuropathy.

PMID- 8752423
TI  - [Clinical, pathologic and molecular genetic studies of patients with hereditary
      motor and sensory neuropathy (HMSN)].
AB  - Clinical, pathologic and molecular genetic studies of Japanese HMSN patients were
      reported. Among 26 HMSN I probands tested, the PMP22 gene region was duplicated
      in 18 (69%). A proband of HNPP, whose PMP22 gene region was deleted, was
      described. A proband with HMSN I was found to have a mutant allele that caused a
      substitution of arginine for glycine at amino acid 93 of PMP22. The mutation was
      located in the transmembrane portion of PMP22. The patient's sural nerve showed
      decrease of large myelinated fibers and frequent segmental demyelination and
      remyelination. A family with HMSN IB was found to have a mutant allele that
      caused a substitution of histidine for arginine at amino acid 98 of Po. The
      mutation was located in the extracellular domain of Po. The sural nerve from a
      proband showed uncompaction of major dense lines, wide-spaced major dense lines,
      and thin myelin sheath relative to axon size. One family of HMSN X with a mutant
      allele that caused a substitution of leucine for serine at amino acid 26 of Cx32
      was found. The mutation was located in the fist transmembrane portion of Cx32. A
      variety of genetic abnormalities, probably underlying pathologic changes of the
      peripheral nerve, found among Caucasians were also noticed among Japanese.

PMID- 8752424
TI  - [Molecular pathology of Charcot-Marie-Tooth disease type 1A: abnormal expression
      of PMP-22].
AB  - In the majority of Charcot-Marie-Tooth disease type 1A (CMT1A) patients, the
      peripheral myelin protein 22 (PMP-22) gene maps within 1.5 megabase duplication
      on chromosome 17p11.2-12. The PMP-22 gene dosage is believed to be a major
      determining factor in the molecular pathology of CMT1A. Median nerve conduction
      velocities were below 35 m/sec in 17 CMT1A patients examined. Northern blot
      analysis showed that the mean relative ratio of PMP-22 mRNA levels in biopsied
      nerves of 5 patients with CMT1A is significantly higher than that in disease
      controls. Immunohistochemical analysis demonstrated that Schwann cell cytoplasm
      including onion bulbs as well as the myelin sheath was positive for PMP-22 in
      some patients with CMT1A, while PMP-22 was expressed only on compact portion of
      the myelin sheath in non-CMT1A patients and normal subjects. A minority of CMT1A
      are known to carry dominant and recessive point mutations in PMP-22. Some
      patients with Dejerine-Sottas syndrome (DSS) also have dominant and recessive
      point mutations in PMP-22. Instead of being two completely distinct disease
      entities, DSS and CMT1A form a spectrum of inherited PMP-22 related neuropathies,
      including hereditary neuropathy with liability to pressure palsies which carries
      a deletion of the PMP-22 gene.

PMID- 8752425
TI  - [Mutation of the myelin Po gene in hereditary motor and sensory neuropathy].
AB  - Charcot-Marie-Tooth neuropathy type 1 (CMT1) or hereditary motor and sensory
      neuropathy (HMSN1) is the most common inherited peripheral neuropathy. Most cases
      show dominant inheritance. CMT1 loci map to chromosome 17 (CMT1A), chromosome 1
      (CMT1B), another unknown autosome (CMT1C) and the X chromosome (CMTX). CMT1A has
      been demonstrated to be associated with a large DNA duplication of 17 p11.2
      including the peripheral myelin protein-22 gene (PMP22) or a point mutation of
      PMP22. Myelin protein zero (Po), the major structural protein of peripheral
      myelin, is another integral myelin membrane protein like PMP22. We have mapped
      the locus of the Po gene to chromosome 1q22-q23 in the region of the CMT1B locus,
      investigated Po as a candidate gene in three families with CMT1B and identified
      that Po is a gene responsible for CMT1B. Dejerine-Sottas disease (HMSN3) has been
      considered as another demyelinating disease. However, we have demonstrated that a
      de novo mutation of Po gene is responsible for some sporadic cases with HMSN3.
      The term "Dejerine-Sottas disease" may have represented the severely affected and
      sporadic cases with CMT. Identification of the primary defect in the diseases
      enables us to classify the peripheral neuropathies based on their etiologies.

PMID- 8752426
TI  - [Multiple system atrophy (MSA)].
AB  - The clinical and pathological features of 47 cases of multiple system atrophy
      (MSA) were analyzed. The mean age of onset was 56.7 (range 40 to approximately
      76) years and mean survival was 5.7 (range 1.5 to approximately 12) years.
      Parkinsonism occurred in 31 cases. Helpful early points to the diagnosis included
      rigid-akinetic type, rapid progression, failure to respond to L-DOPA and other
      signs such as autoromic dysfunction, cerebellar ataxia and pyramidal signs, but
      these were not always present. T2 weighted MR images demonstrated decreased
      signal in the putamen and/or slit-hyperintensity in the outer margin of the
      putamen. These clinical and MRI findings are useful in the differential diagnosis
      between Parkinson's disease and MSA. Glial cytoplasmic inclusions (GCIs) were
      found in all 21 cases, but not in control brains. Several types of neuroral
      inclusion were also observed; large neuroral cytoplasmic, small neuroral
      cytoplasmic and nuclear inclusions. GCIs were labeled by antiubiquitin, anti
      alpha and beta-tubulin and antitau antibodies. Large neuronal cytoplasmic
      inclusions (NCIs) observed in the pontine nuclei were positive with only
      antiubiquitin antibody.

PMID- 8752427
TI  - [Progressive supranuclear palsy].
AB  - Progressive supranuclear palsy (PSP) was a distinct clinicopathological syndrome
      described by Steele, Richardson and Olszewski in 1964. In 1974, Narabayashi and
      the present author described a syndrome of levodopa unresponsive pure akinesia or
      freezing without rigidity or tremor affecting gait, hand writing and speech. In a
      series of subsequent reports in Japan, evidence has indicated that pure akinesia
      often represents a pre-oculomotor form of PSP. In this sense, the syndrome of
      pure akinesia/PSP is proposed. The pathogenesis and etiology of PSP and related
      conditions remain to be cleared.

PMID- 8752428
TI  - [Diffuse Lewy body disease].
AB  - Diffuse Lewy body disease (DLBD), which we have proposed since 1976, has received
      great attention among both researchers and clinicians. Recently, it was reported
      by some English and American research groups that DLBD is the second most
      frequent dementing illness in the elderly, following Alzheimer-type dementia
      (ATD). Our recent research of 79 autopsied dementia cases in a hospital disclosed
      that DLBD (15.4%) was the second most common degenerative dementia, following ATD
      (43.6%). In 1980 we proposed Lewy body disease, and classified it into three
      types: brain stem type, transitional type, and diffuse type. Diffuse type of LBD
      is now called DLBD. In 1990 we divided DLBD into two forms: common form and pure
      form. The common form of DLBD has more or less Alzheimer pathology, and pure form
      has none. Very recently, we proposed the cerebral type of LBD, in which numerous
      Lewy bodies are found in the cerebral cortex and amygdala, but no PD pathology is
      present in the brain stem. Therefore, LBD is now classified as follows: [table:
      see text]

PMID- 8752429
TI  - [Cerebrovascular parkinsonism--clinicopathologic study].
AB  - We investigated the existence, clinical symptoms, and brain pathology of
      cerebrovascular parkinsonism. In this study, clinicopathological criteria of
      cerebrovascular parkinsonism was defined as follows: 1) at least 2 or more
      symptoms from the following 4 symptoms: tremor, rigidity, akinesia or
      bradykinesia, and short stepped gait or freezing, 2) no depigmentation, no Lewy
      body at the substantia nigra, no other degenerative disease, and 3) existence of
      cerebrovascular lesions. Among consecutive 4,000 autopsy series in the elderly,
      clinicopathologically confirmed cerebrovascular parkinsonism was found in 24
      patients with mean age of 80 years. Cerebrovascular parkinsonism was
      characterized by the short-stepped gait as initial symptoms, absence of the
      resting tremor, lead-pipe rigidity, the symmetry of findings, and negative
      response to levodopa. Pseudobulbar palsy was observed in 54%, pyramidal findings
      in 63% of the cases. Most cases had multiple vascular lesions of the basal
      ganglia, but the distribution of lesions was not different from that in the cases
      of progressive subcortical vascular encephalopathy of Binswanger type without
      parkinsonism. Diffuse pallor and the loss of oligodendrocytes in the frontal
      white matter observed in the cerebrovascular parkinsonism suggested that the
      symptoms of parkinsonism resulted from the white matter damages in the frontal
      lobe.

PMID- 8752430
TI  - [Corticobasal degeneration: symptomatological, brain-imaging and
      electrophysiological studies].
AB  - Eight cases of clinically diagnosed corticobasal degeneration (CBD) were studied
      with reference to their symptomatology, brain-imagings and electrophysiological
      findings. The diagnosis was based on the combination of limb-kinetic apraxia
      (cortical sign), akinetic-rigid sign (extrapyramidal) and their unilateral
      predominance. Magnetic resonance imaging (MRI) and 123I-IMP or 99mTc-HMPAO SPECT
      findings were used to reinforce the diagnosis. The age at onset of 8 cases (4
      males, 4 females) was 61 to 80 years (mean 66). Other common symptoms on
      admission consisted of dysequilibrium (8 cases), dysarthria (8), grasp reflex
      (6), supranuclear gaze palsy (6), tremor (6), limb dystonia (6) and alien limbs
      (5). MRI revealed parietal (3 cases) or frontoparietal (3) atrophy. SPECT showed
      decrease in cerebral blood flow in frontoparietal (3 cases) or
      frontoparietotemporal lobes (5). SPECT surpassed MRI to detect unilateral
      predominance of the lesions. With magnetic stimulation of the head and neck
      central motor conduction time (CMCT) was normal, while motor inhibitory periods
      (IPs) were significantly shorter in CBD patients compared with those in normal
      controls and the patients with Parkinson's disease. In 3 patients with reflex
      myoclonus, giant SEPs were not evoked, though with positive C-reflex, suggesting
      an elevated excitability of cerebral cortex unrelated to the production of giant
      SEPs.

PMID- 8752431
TI  - [Intravascular malignant lymphomatosis].
AB  - Based on our personal experience of two cases of intravascular malignant
      lymphomatosis (IML) and a review of 128 cases in the literature, the
      possibilities for clinical diagnosis and successful treatment of this condition
      are discussed. IML usually presents with hemiparesis or progressive dementia and
      then with disturbances of consciousness. Paraparesis and dysuria due to spinal
      cord involvement are not rare. Since increased levels of blood sedimentation
      rate, CRP, serum LDH, and CSF protein are often observed in the patients, a
      diagnosis of IML must be included among the list of differential diagnoses when
      these findings are encountered in a patient presenting with clinical features
      similar to those of cerebrovascular diseases or multiinfarct dementia. The
      diagnosis must be confirmed histologically, so that an appropriate treatment can
      be initiated early in the course of the disease. Skin biopsy is indicated when
      skin eruption is present. Autopsy records of patients have revealed involvement
      of intravascular lymphoma to the kidney, adrenals, lungs and liver in more than
      80% of cases. It is suggested therefore that biopsies are performed for these
      organs. Muscle biopsy can also be useful for making a diagnosis. Since autopsy
      studies have revealed swelling of the adrenals in some cases, including ours, CT
      or MRI images of the adrenals might be of importance. Regarding treatment,
      chemotherapy must be indicated. However, this has so far shown either no or only
      a temporary efficacy, partly because of the delay in reaching a diagnosis. A cure
      for IML could be expected through early initiation of combined treatment with
      various chemotherapeutic agents in the near future.

PMID- 8752432
TI  - [Neuroimaging findings in intravascular malignant lymphomatosis].
AB  - We reviewed the neuroimaging studies of five patients with intravascular
      malignant lymphomatosis (IML). All five patients had cerebral symptoms and three
      had spinal cord or root symptoms. Initial brain CTs, in two patients at the onset
      of cerebral symptoms, were normal. Brain MR imaging, conducted in four patients
      during the course of IML, showed multiple white matter lesions which were
      hyperintense on T2-weighted images. Some of the lesions involved cerebral
      cortices, and some had mass effect. Serial MR imaging was performed in three
      patients, and the lesions decreased in size during steroid or CHOP therapy. Gd
      DTPA-enhanced study which was conducted in one patient demonstrated enhancement
      of the white matter lesions. Review of the literature revealed various CT or MR
      findings; single or multiple cortical or subcortical lesions with or without mass
      effect, periventricular lesions, and spinal cord lesions. Lesions may or may not
      be enhanced. Because neuroimaging findings are non-specific, correct diagnosis is
      difficult to make by imaging studies alone. One should always consider the
      possibility of IML in the interpretation of radiological images.

PMID- 8752433
TI  - [Pathology of intravascular malignant lymphomatosis].
AB  - On the basis of six necropsied cases of intravascular malignant lymphomatosis
      (IML), we elucidated its pathological characteristics. In the brain of IML,
      multiple softened areas of various size were observed, dominantly in the white
      matter of the cerebral hemisphere, which showed bilateral distribution with no
      relation to the supply area of the large vessels and intermingled fresh and old
      lesions. The spinal cord was one of the most often involved areas in IML,
      particularly at the lumbosacral segmental level. The origin of the tumor cells,
      based upon the findings that the tumor cell of all our cases were positive for SL
      26, LN1, and LN2, were considered to be B-cell. We speculated that not only the
      circulatory failure due to the tumor cells which filled the vascular lumen, but
      also circulatory disturbances due to thrombosis, thickening of the intima and
      angiitis were significant findings for the necrosis in IML. IML is an important
      disease as the fourth type of central nervous system involvement due to malignant
      lymphoma, in addition to primary malignant lymphoma of the brain, meningeal
      lymphomatosis, compression of the spinal cord caused by extradural metastasis of
      lymphoma.

PMID- 8752434
TI  - [Molecular genetic analysis of intravascular malignant lymphomatosis cells].
AB  - In this study, we examined the VDJ region of the immunoglobulin heavy chain (IgH)
      gene in intravascular malignant lymphomatosis (IML). The VDJ regions were
      amplified using the polymerase chain reaction (PCR) with consensus primers of the
      V and J regions of the IgH gene. Specimens from all the IML cases produced a
      monoclonal band. Specimens from metastatic carcinomas, brain tumors and normal
      tissues produced no monoclonal amplification. By cloning and sequencing the
      amplified VDJ regions, we have determined nucleotide sequences of rearranged
      regions of the IgH genes. In addition, we also examined tumor suppressor genes.
      The polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)
      analysis revealed no abnormal migration in exons 5 to 8 of the p53 gene, exon 2
      of the p16 gene and exon 2 of the p21 gene. These findings suggested that
      mutation of p53, p16 and p21 genes is rarely related with the tumorigenesis of
      IML. The presence of Epstein-Barr virus (EBV) was also analyzed using PCR. EBV
      DNA was detected in one of five IML specimens. This result indicates that IML may
      be associated with EBV.

PMID- 8752435
TI  - [Progress and view of the studies on intravascular malignant lymphomatosis].

PMID- 8752436
TI  - [Molecular genetics of myotonic dystrophy].
AB  - The gene for myotonic dystrophy (DM) was found to be an expansion of an unstable
      CTG repeat located in the 3'-UTR of the putative protein kinase gene. In the
      general population 5 approximately 37 copies of the repeat are present, but in DM
      patients the repeat number varies from 50 up to thousands of copies. We have
      determined the copy number of the CTG repeat and made a haplotype using the
      closely linked markers to the CTG repeat in 93 Japanese DM families. The absolute
      linkage disequilibrium was observed in patients from both populations, between
      the DM gene and the linked markers. These data strongly suggest a common origin
      of Caucasian and Japanese DM alleles. The genetic analysis of apparently sporadic
      occurrence of DM in a family in which two asymptomatic members have been shown to
      have a number of repeats corresponding to premutation alleles, 44 and 46 CTG
      alleles. These data strongly suggest that (CTG) 19 approximately 37 may act as a
      predisposing allele for successive DM generations and that there is a premutation
      allele for DM, as predicted in a multistep model for etiology of this disorder.

PMID- 8752437
TI  - [Myotonin protein kinase].
AB  - The mutation underlying myotonic dystrophy is the expansion of polymorphic CTG
      repeat in the 3'-noncoding region of the myotonin protein kinase (MtPK) gene
      mapping to chromosome 19q13.3. A full-length cDNA of human MtPK was cloned and
      expressed in COS-1 cells. MtPK is recovered from the COS cell extract as a 70 kDa
      protein, which coincides with the size deduced from the predicted amino acid
      sequence. Biochemical characteristics of MtPK expressed in COS cells and its
      expression are investigated.

PMID- 8752438
TI  - [Abnormalities of N-linked oligosaccharide moieties of glycoproteins in patients
      with myotonic dystrophy].
AB  - Myotonic dystrophy (MyD) is an inheritant disease which results from an abnormal
      expansion of trinucleotide repeat of myotonin protein kinase. MyD has been
      considered as one of membrane diseases as several functional disturbances were
      detected on the plasma membranes in patients with MyD. We reported here that some
      proteins and tissues in patients with MyD took only incomplete processing of N
      glycans. The characteristic feature of the oligosaccharide moieties was so unique
      that N-glycans of glycoproteins such as immunoglobulin G, proteins on the
      erythrocyte membrane and the insulin receptor revealed reduced content of N
      acetylneuraminic acid and galactose. In other words, these glycoproteins in
      patients with MyD had N-linked oligosaccharides which terminated with N
      acetyglucosamine at the non-reducing ends. These specific defect of glycosylation
      may indicate the disturbances of the sarcoplasmic reticulum or the Golgi
      apparatus and be one of the factors which construct the membrane disorder
      observed in patients with MyD.

PMID- 8752439
TI  - [Respiratory failure: respiratory disorder during sleep in patients with myotonic
      dystrophy].
AB  - Myotonic dystrophy (MyD) patients have been reported to show severe nocturnal
      desaturation related to sleep respiratory disorders. However, the reason of
      respiratory failure in MyD has remained unclear. In this study, ten patients with
      MyD underwent overnight polysomnography to evaluate the mechanisms which would
      cause respiratory failure, compared with Duchenne muscular dystrophy (DMD)
      patients in these three views: 1) sleep-related nocturnal desaturation, 2)
      histopathological evaluation of respiratory muscles, and 3) abnormalities of
      respiratory center. Nocturnal desaturation was more prominent in MyD rather than
      DMD. Apnea-hypopnea index (AHI) was higher in MyD than DMD. Type of respiratory
      disorder during sleep was mainly central apnea-hypopnea pattern, including Cheyne
      Stokes respiration. In histopathological findings, central core change in
      respiratory muscle related to respiratory muscle fatigue was found less
      frequently in MyD than DMD. In respiratory center function, MyD showed
      hyporesponse to both alveolar hypercapnic and hypoxic stimulation. However, DMD
      showed normal response to both stimulations. We concluded that respiratory
      failure in patients with MyD would be attributed to respiratory center disorder
      rather than respiratory muscle weakness, which is the main cause of respiratory
      failure in patients with DMD.

PMID- 8752440
TI  - [Prognosis for myotonic dystrophy].
AB  - Although the genetic basis of myotonic dystrophy (MD) has recently been
      clarified, data on prognosis and causes of death are few. To assess the relation
      between the age of onset and the degree to which activities of daily living (ADL)
      were affected, we studied statistically 586 patients with MD, who were registered
      in the database in hospitals of Japan in 1985. Many of the young onset patients
      had a long duration of illness, and many of the long-term patients showed the
      more severely affected ADL. When we adjusted the duration of illness, using the
      Mantel extension method, many patients whose age of onset was older had poorer
      ADL than the younger onset ones. To clarify the causes of death in MD, we
      collected data on 72 patients who succumbed to it from answers to questionnaires
      sent to all councilors of the Japanese Society of Neurology and the Japanese
      Society of Child Neurology in 1994. Before their deaths, among 32 MD cases unable
      to sit up, 16 (50%) died from respiratory involvement (respiratory failure and
      pneumonia), 8 (25%) from dysphagia (i.e., aspiration pneumonia and choking) and 2
      (6%) from cardiac involvement. Moreover, among 25 cases that could sit up, 9
      cases (36%) died from dysphagia, 4 (15%) from respiratory involvement and 2 (8%)
      from cardiac involvement. Dysphagia and cardiac involvement are often the causes
      of death in the early stage. To avoid these complications, management of
      swallowing and careful cardiac control is essential in patients with MD.

PMID- 8752441
TI  - [A view for understanding the pathogenesis of multiple sclerosis].
AB  - There are 2 hypotheses for understanding the pathogenesis of multiple sclerosis
      (MS), viral and autoimmune ones. Although antibodies to many viruses are
      elevated, an MS-specific virus has not been found and none of conventional
      viruses has been definitely located in MS lesions. Thus, viruses, if involved,
      seem to be indirect. Autoimmune encephalomyelitis (EAE) has represented main
      aspects of MS such as inflammatory demyelinating plaques, spontaneous onset,
      remission and relapse. This was proven by transgenic mice that express T cell
      receptor genes of myelin basic protein (MBP)-specific encephalitogenic T cells
      (Goverman et al, 1993). The animals developed spontaneous EAE and relapsed when
      kept in the conventional condition. Otherwise, it was necessary to inject
      bacterial antigens, when they were kept in an SPF condition. We have shown that
      MBP89-101 specific encephalitogenic T cell clones are polyreactive (Kozovska et
      al, submitted). In MS, T cell responses to MBP and proteolipid protein (PLP) have
      been studied and certain T cell immunodominant regions are suggested. Some of the
      MHC-class II-restricted and MBP peptide-specific T cell clones responded to
      several viral antigens (Wucherpfenning and Strominger, 1995). Thus, it is highly
      probable that autoaggressive T cells are polyreactive and activated by viral and
      other antigens. I believe that this is the central mechanism operating in MS.
      Before reaching this conclusion, we must show that the MBP- or PLP-specific
      polyreactive T cells are indeed encephalitogenic. In order to prove this, we must
      establish an animal model, humanized mice.

PMID- 8752442
TI  - [Multiple Sclerosis--diagnosis and its problems].
AB  - Multiple sclerosis (MS) is an inflammatory central nervous system (CNS)
      demyelinating disease, though the etiology still remains unknown. To make a
      diagnosis of MS is largely based on clinical features which are characterized by
      multiplicity of CNS symptoms and signs in time and space. However, there have
      been some questions and problems about the diagnosis of MS. There are a great
      diversity of MS clinical forms, such as relapsing and remittent type, chronic
      progressive type (primary or secondary), Devic type or Balo type, so on. In
      particular, optic-spinal form of MS is undoubtedly common in Japan and other
      Asian countries, compared with American and Northern European countries. To make
      a correct diagnosis of MS, it is important to rule out other diseases mimicking
      MS, such as tumors, cerebrovascular diseases, several myelopathies, collagen
      diseases, sarcoidosis, Wilson disease, so on. Nevertheless, it is hard to
      differentiate MS from some other MS-mimicking diseases, for example CNS Sjogren
      disease and antiphospholipid antibody syndrome. Since MRI detects demyelinating
      lesions within CNS with high sensitivity, MRI examination has a great impact on
      the diagnosis, etiological investigation and therapeutic trial of MS.

PMID- 8752443
TI  - [Multiple sclerosis viewed from the point of HTLV-I associated myelopathy].
AB  - Several interesting facts are observed in multiple sclerosis (MS) when it was
      viewed from the point of HTLV-I-associated myelopathy (HAM). The distribution of
      the two diseases is completely segregated each other and deeply related to races
      as shown in the figure. Both diseases have significant linkage to HLA; HAM being
      linked to HLA-DR1 with relative risk 3.8 whereas MS being linked to HLA-DR2 with
      relative risk 3.3. The clinical features of 363 HAM patients and 479 MS patients
      were compared using statistical multivariate analysis and patients with MS and
      HAM appeared in two distinct clusters. From the neuropathological point of view,
      MS is a disorder specifically related to demyelination and HAM is a disorder
      closely related to T-cell mediated inflammation. The biggest difference between
      HAM and MS is that the causative agent is known in HAM but not in MS. The studies
      on HAM will hopefully help to understand the pathomechanisms of MS.

PMID- 8752444
TI  - [Immunotherapy of multiple sclerosis: the use of magnetic resonance imaging in
      the evaluation of clinical trials].
AB  - Magnetic resonance imaging (MRI) is being used increasingly as a measure of
      outcome in monitoring the efficacy of treatment for multiple sclerosis (MS). A
      major advantage of MRI is that it easily detects subclinical disease activity and
      thus serial MRI provides an objective and sensitive tool. In the treatment of
      acute attacks, corticosteroids are widely used to speed recovery from disability.
      Recently, methylprednisolone administered in megadose pulses was reported to
      reduce the conversion rate of patients with optic neuritis to MS. The beneficial
      effect of treatment was most apparent in patients with abnormal MRI scans. Among
      the immunosuppressive or immunomodulatory drugs that have been used to prevent
      progression or reduce relapses, interferon beta 1b is the first medication
      confirmed to reduce accumulations of MRI detected lesions. In a cyclosporin
      treatment trial, MRI studies failed to show a significant benefit. Other
      therapies that require further definitive study include intravenous
      cyclophosphamide and oral methotrexate or azathioprine. A multicenter double
      blind clinical trial with mizoribine is in progress in Japan and the results will
      be known some time during the first half of 1997.

PMID- 8752445
TI  - [Suppression of experimental autoimmune encephalomyelitis with antibodies against
      adhesion molecules].

PMID- 8752446
TI  - [Multiple sclerosis: update on current therapies].
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the
      central nervous system (CNS). It is widely accepted that MS is caused by an
      autoimmune response against myelin. The most common treatment for acute attacks
      or active state of exacerbation of MS is intravenous pulsed methylpredonine
      therapy followed by immunosuppressive agents, such as corticosteroid or
      azathioprine. Recently, recombinant interferon beta-1b, or natural form of
      interferon beta-1a has been reported to have an effect in MS. We reported
      preliminary results on a new method of lymphocytapheresis using a leucocyte
      adsorption column to treat MS patients in active state. In some MS patients,
      immediate improvement was observed following lymphocytapheresis. The more
      selective therapeutic trials including monoclonal antibodies against chimeric
      CD4, anti-antigen receptors antibody, anti-adhesion molecules antibody, and the
      induction of tolerance to myelin basic protein, or immunity to TCR antagonist
      peptides were reported in several institutes based on new strategies in
      immunotherapy.

PMID- 8752447
TI  - [Spinal neural mechanisms in voluntary movements].
AB  - Spinal circuits are utilized not only in reflex movements but also in voluntary
      movements. Their functions are many-fold such as reciprocal inhibition, output
      control of motoneurones, integration of central and peripheral inputs in
      motoneurones, or increase in selectivity of muscle contraction etc. The brain
      controls the activity of spinal circuits depending on the movements required, by
      controlling the activity of interneurones in the reflex pathways. In the case of
      the soleus, the activity of reciprocal Ia inhibition and Ib inhibition increases
      during voluntary contraction of the antagonists. The increase in both inhibition
      takes place during contraction as weak as 1-2% of the maximum, suggesting that
      the interneurones can be fired by the descending commands alone without any
      peripheral inputs. Such central control is beneficial in suppressing stretch
      reflexes in the antagonistic muscles which follows voluntary movements. On the
      other hand, the activity of recurrent inhibition of the soleus is enhanced during
      weak contraction of the muscle, but depressed during medium strength contraction
      and strongly depressed during strong contraction. Such supraspinal control of
      Renshaw cells improves the balance between the preciseness in controlling
      movements and the crude muscle power required. Importance of spinal circuitry
      during voluntary movement should be emphasized.

PMID- 8752448
TI  - [Analysis of cortical excitation and inhibition using transcranial magnetic
      stimulation].
AB  - The method of magnetic transcranial stimulation of the motor cortex produces both
      excitatory and inhibitory effect. Definition of excitability and inhibitory
      threshold represents clinically useful indicator. In order to reduce variability
      of the thresholds, it is important to notice mental activity, posture, type of
      magnetic stimulator, involuntary movement, muscle tonus and age. Excitability
      threshold was elevated in patients with stroke and reduced in patients with
      epilepsy. Enhancement of motor excitability by subthreshold magnetic stimulation
      of the motor cortex prior to voluntary movement was observed during simple
      reaction time measurement. Reaction time can be divided into a period of resting
      condition and the premotion facilitatory effect in the 50 approximately 60 ms
      after the target stimuli. In patients with Parkinson's disease, the prolongation
      of reaction time is due to a prolongation of a period of premotion facilitatory
      effect. Jerk-locked MEP is a useful technique to evaluate a change of motor
      excitability after voluntary or involuntary movement. To record jerk-locked MEP,
      magnetic stimulation of the motor cortex is delivered at varying intervals after
      the onset of the EMG activity. We classified the cortical reflex myoclonus into
      three forms according to changes of motor excitability after C reflex.

PMID- 8752449
TI  - [Motor reorganization in the motor cortex].
AB  - Plasticity within the human central motor system has been studied with
      transcranical magnetic stimulation in patients with peripheral and central
      nervous diseases. In 4 patients with a complete upper limb palsy due to traumatic
      cervical root avulsion, surgical anastomosis of intercostal to musculocutaneous
      nerves was performed to restore function in the biceps brachii muscle. The motor
      unit discharges became independent from respirations gradually over 1 to 2 years.
      Motor cortex mapping of the reinnervated biceps muscle showed a gradual change
      over 4 to 33 months from the area of the intercostal muscles to that of the arm
      area, which was more lateral on the motor cortex. These findings suggest that
      reorganization of the motor cortex to arm flexor muscles occurs following
      peripheral nerve anastomosis. In 8 patients with chronic cerebral infarction with
      hemiplegia. Four of 8 patients did not show MEPs in paralytic hand muscles by
      contralateral cortex stimulation, but showed small MEPs by ipsilateral cortex
      stimulation. These cases had the huge cortical infarction unilaterally in CT.
      Another four of 8 patients showed small MEPs in paralytic hand muscles by
      contralateral cortex stimulation, but no MEPs by ipsilateral cortex stimulation.
      These cases had the subcortical infarction unilaterally in CT. These findings
      suggest that reorganization of motor cortex following unilateral cerebral
      infarction.

PMID- 8752450
TI  - [The role of the basal ganglia in movement control].
AB  - It is now widely accepted that the basal ganglia (BG) are functionally organized
      with several segregated loops which start at a certain area in the cortex and
      project back to the same area in the cortex through the thalamus. The detailed
      functional organization of the BG motor loop has been described and used
      successfully to explain the mechanism of hypo- and hyper-kinetic disorders caused
      by BG disorders. Recent physiological and anatomical studies have provided new
      information concerning the function of these nuclei. The indirect pathway from
      the striatum to the external globus pallidus and then to the internal globus
      pallidus may be much more important than previous thought. The subthalamic
      nucleus may transmit excitatory input from the cortex as well as acting as a
      driving force on the globus pallidus. The role of BG output on the thalamus may
      not be to transfer information to the cortex via thalamocortical neurons, but
      rather to modulate the activity of cortico-thalamocortical loops. By varying it's
      discharge rate, the BG can change the membrane potentials of thalamocortical
      neurons which may result in focusing the activity of a specific cortico-thalamo
      cortical loop and/or switching it to another.

PMID- 8752451
TI  - [Noninvasive study of cortical neuronal mechanism in voluntary movements: role of
      basal ganglia and cerebellum].
AB  - Voluntary movements can be classified into the two categories depending on how
      those are initiated; ones initiated internally, and others triggered or paced by
      external stimuli. Central neuronal mechanisms involved in those preparation and
      execution could be represented by movement-related cortical potentials (MRCP) or
      Bereitschaftspotential (BP), and contingent negative variation (CNV),
      respectively. The both potentials, as the field potentials, can be recorded with
      long time constant, and represent transient changes of the membrane potentials of
      the cortical neurons. In patients with the lesion at the cerebellar efferent
      system, the BP disappeared completely whereas the late CNV was normally seen. In
      patients with parkinsonism, in contrast, the late CNV was significantly smaller
      in amplitude in severe than in mild symptom group. Recent subdural recording in
      epilepsy patients demonstrated that the BP and late CNV were commonly generated
      from the primary and supplementary motor areas, and that late CNV also arose from
      the frontal association cortices (mesial, basal and lateral prefrontal areas). It
      is therefore suggested that subcortical generating mechanism is different for the
      late CNV and BP although both commonly share at least some cortical generators,
      and that the basal ganglia are most likely responsible for the generation of the
      late CNV and the cerebellar efferent system for the generation of the BP.

PMID- 8752452
TI  - [Movement-related cortical potentials (MRCPs) and voluntary movement--clinical
      usefulness of MRCPs].
AB  - The gradient of negative slope (Ns') changed in parallel with the velocity of
      step movement in normal individuals. We can not evaluate the MRCPs without
      considering this factor among patients and/or subjects. We recorded the MRCPs of
      thirty nine patients with cerebellar ataxias and sixteen patients with Parkinson
      disease (PD). Goniometer was attached on the patient's wrist to measure the
      velocity of the wrist movement. In the patients with spinocerebellar degeneration
      with denate nucleus lesion (Machado-Joseph disease, DRPLA, MERRF, dyssynergia
      cerebellaris myoclonica, galactosialidosis), the gradients of Ns' were reduced,
      although the movements themselves were as fast as normal control. In the patients
      with spinocerebellar degeneration without this lesion, the MRCPs were able to
      record as normal control, and their gradients of Ns' became steeper according to
      the increase of the movement angular velocity. On the contrary, in the patients
      with Parkinson disease, the gradients of Ns' were steeper in the patients with
      slow movement than in those with fast movement. The MRCP helps us to investigate
      the pathophysiology of the movement disorders. It is desirable that physiological
      data on the MRCP are extensively accumulated.

PMID- 8752453
TI  - [Molecular genetics of Huntington's disease].
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder which is
      clinically characterized by chorea, cognitive decline, and emotional disturbance;
      it is inherited in an autosomal dominant manner. The HD gene maps to chromosome
      4p16.3. Our linkage analysis demonstrated a significant genetic linkage between
      Japanese HD families and the flanking markers, D4S127, D4S43. The molecular basis
      of the disease is an expansion of CAG repeat in the huntingtin gene. We performed
      molecular analysis of the repeat in Japanese HD patients and normal controls. The
      size of the CAG repeat ranged from 37 to 95 repeats in affected subjects and from
      seven to 29 in normal controls. A significant correlation was found between the
      age of onset and the CAG expansion. The length of the expanded repeat is unstable
      in meiotic transmission and large increases occur in paternal transmission. At
      the same time the CCG repeat polymorphism adjacent to the CAG repeat was analysed
      and haplotypes of HD chromosomes were identified. Striking linkage disequilibrium
      was found between the CAG repeat expansion and an allele of (CCG)10 in Japanese
      HD chromosome. It is distinct from that described previously in western
      populations. Western HD chromosomes strongly associate with an allele of (CCG)7.

PMID- 8752454
TI  - [Prevalence and founder effect of Huntington's disease in the San-in area of
      Japan].
AB  - After the DNA diagnosis, we evaluated the prevalence of Huntington's disease (HD)
      in the San-in area of Japan, and confirmed the founder effect. The population of
      the area was 1,387,000 on October 1st, 1993. There were 10 patients with HD in
      the San-in area, who were diagnosed clinically. They all had involuntary
      movement, mental disturbance, changes of character and atrophy of the caudate
      nucleus. However, one of the patients showed no positive family history of HD.
      The other nine patients had members with HD in their families, although those
      family members of the patients had already died. The expansion of the CAG repeat
      was observed in nine of the patients. In the patient who had no positive family
      history, expansion of the CAG repeat was not seen. According to the nine patients
      with expansion of the CAG repeat, the prevalence was 0.65/100,000. Haplotypes
      using polymorphism markers of D4S111 and D4 S136 were studied. The haplotypes
      which were observed in only 2.7% of the normal population were shown in all nine
      HD patients. Thus, the obvious disequilibrium was seen. These results suggested a
      common ancestor of these HD patients.

PMID- 8752455
TI  - [Ethical aspect of predictive gene diagnosis].
AB  - Progress of gene diagnosis has made it possible to predict whether a man develops
      any particular disease. The typical case is Huntington's disease. However,
      predictive gene diagnosis profits anything? Not a few persons at risk of the
      disease do not want to receive predictive diagnosis. Some investigators assert
      that if informed consent is available, there is no problem to do the test.
      However, to force the client to decide whether to receive or not the diagnosis is
      a great cruelty for them. Investigators must recognize their pitiable states.
      Predictive gene diagnosis offers an important problem whether precognition in
      general is really worthwhile. Cicero told us "It is no use to foresee the future,
      if there is no profit", and today this sentence is still alive. Today's medicine
      has inclined to neglect patients themselves. Men, who have paid the highest
      respect for reason and almighty sciences, must remember the following
      philosophical prose of Alexander Pope: "Know then thyself, presume not God to
      scan; The proper study of Mankind is Man."

PMID- 8752456
TI  - [Some problems on neuropathology of Huntington disease].
AB  - The most striking neuronal loss in the brains of Huntington disease (HD) occurs
      in the striatum, predominant in the caudate nucleus. However, pathogenesis of
      this disease is supposed to be mainly based on the process of "simple atrophy" in
      the whole brain neurons and their axons. Therefore, although the autopsied brains
      of HD are atrophic and their weight are light, histopathology based on the
      classical method shows few abnormal findings in the cerebrum. Against this fact,
      "numeric atrophy" of the neurons occurs in the striatum of chorea acanthocytosis.

PMID- 8752457
TI  - [Huntington's disease: trinucleotide disease or polyglutamine disease?].
AB  - Huntington's disease (HD) is associated with expansion of an unstable CAG repeat.
      Using antibodies against the synthetic peptide corresponding to the sequence of
      HD gene IT15, we have identified the HD gene product in normal lymphocytes as a
      approximately 350kDa protein by immunoblot analysis. Moreover, when a modified
      SDS-PAGE using a low concentration of methylenbisacrylamide was run longer,
      abnormal immunoreactive bands larger than normal ones were found exclusively in
      HD samples. We also found double bands in HD brain homogenate samples. Recently
      on the other CAG repeat diseases, such as SCA1 and DRPLA, abnormal gene products
      were also reported. These results demonstrate the existence of the expanded CAG
      repeat gene products and open a possibility that the expanded polyglutamine
      stretch may really participate in the pathological process of the CAG repeat
      diseases.

PMID- 8752458
TI  - [Deficiency of human ciliary neurotropic factor (CNTF) is not causally related to
      amyotrophic lateral sclerosis (ALS)].
AB  - Ciliary neurotrophic factor (CNTF) promotes the survival of motor neurons in
      vitro and in vivo. A recent report showed that disruption of the CNTF gene in
      mice caused motor neuron degeneration. We have found a null mutation in the human
      CNTF gene. The mutated allele shows a G to A transition producing a new splice
      acceptor site and the resulting mRNA species codes for an aberrant protein.
      Analysis of tissue samples demonstrated that the mutated allele expressed only
      the mutated mRNA species. In 391 Japanese people tested, 61.9% were normal
      homozygotes, 35.8% heterozygotes and 2.3% mutant homozygotes. The distribution of
      the three genotypes is similar in healthy and neurological disease subjects
      including ALS patients. Our findings indicate that CNTF deficiency is not
      causally related to ALS.

PMID- 8752459
TI  - [Familial amyotrophic lateral sclerosis and mutations in the Cu/Zn superoxide
      dismutase gene].
AB  - Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder affecting
      primarily upper and lower motor neurons. In all cases of ALS, approximately 5-10%
      of cases are familial (FALS). Missense mutations in the Cu/Zn superoxide
      dismutase (SOD1) gene on chromosome 21 have been demonstrated in some families of
      FALS since 1993. We have also identified a novel missense mutation (substitution
      of Thr for Ala4) in exon 1 in a Japanese FALS family, and clarified the
      pathological findings of a patient in this family were typical of FALS with
      posterior column involvement. However, the mechanism by which the mutations in
      SOD1 lead to ALS is unknown. It is now clear that the mutations in SOD1 reduce
      total SOD activities only by 30-60%, and there is doubt whether a reduction in
      enzymatic function of this magnitude suffices to cause the neuronal loss.
      Recently, transgenic mice expressing the mutant SOD1 demonstrate motor neuron
      degeneration despite an increased level of SOD activity. The process of motor
      neuron degeneration in FALS might be mediated by some novel functions of the
      mutant SOD1 protein.

PMID- 8752460
TI  - [Disappearance of ALS from Guam: implications for exogenous causes].
AB  - The author reports the disappearance of amyotrophic lateral sclerosis (ALS) from
      Guam over past 30 years, which coincided with rapid changes in the ecology,
      socioeconomy, and westernization of the life style. This slow but steady decline
      is believed to be the consequences of radical changes from food collection to
      wage-based life style and dietary improvement in recent years and elimination of
      exogenous factors. Those risk factor(s) are believed to be the environmental
      trace metals which must have triggered the accelerated oxidative stresses in the
      motor neurons of genetically susceptible population. Changing Epidermiology: 1.
      The annual incidence of 70/100,000 in 1960s down to 7/100,000 in 1990s, and
      remained unchanged for past 15 years. 2. Upward shift of age at onset by 10 years
      and at death by 8 years and even out of sex ratio. 3. Birth cohort analysis
      showed less risks for those born after 1920. No ALS cases born after 1945. 4. No
      increase in the incidence of ALS among non-Chamorros transients of Guam and
      Marianas during W.W.II. 5. Long-term resident non-Charmorro and half-Chamorros on
      Guam are also affected. 6. Charmorro migrants to U.S. Mainland are affected after
      long absence from Guam. 7. Incubation period for both ways is estimated to be 18
      approximately 20 years. 8. Other forms of dementias like Alzheimer disease (AD)
      and vascular dementias are on the rise and the leading cause of death is cerebro-
      and cardiovascular diseases. 9. ALS is also declining in past 10 approximately 15
      years in Kii peninsula, and West New Guinea. Changing Ecology of Guam: 1. One
      third of Island land was used for construction of huge military bases after
      W.W.II. 2. Urbanization of villages including concrete houses, deep well water
      supply, sewage, and electrification. 3. Tourism boom: high-rise hotels,
      development of 7 golf courses and other recreational facilities resulted in loss
      of flora and erosions of soil. Socioeconomic Changes: 1. Shift in population
      demography; Efflux of Chamorros and influx of aliens; Chamorros less than 50% by
      1990. 2. Tourists passed 1 million in 1994. 3. Automobiles 1 car/1.5 person. 4.
      Westernization: After W.W.II, almost free access to Military Commissary for
      imported food and appliances. 5. Life style: from food collection to wage-based
      society. Genetic Studies: 1. Familial aggregations, but no clear-cut Mendelian
      inheritance. 2. Segregation analysis: no absolute genetic or environmental cause
      but additive gene component may play a role in genetic susceptibility and basis
      for geographical clustering. 3. Absence of Apo-E or Mu/Zn SOD genes. 4. Recent
      discovery of mtDNA Complex I deficiency in Parkinsonism-dementia cases suggests
      mitochondrial DNA abnormality. Comparative Environmental Studies: 1.
      Environmental studies in three hyperendemic areas in the Western Pacific--Kii,
      Marianas, and west New Guinea, where strikingly high incidences of ALS is known
      to occur, found the identical geochemical environment--low Ca, Mg, and Zn and
      high A1, Mn, Fe, Si, in the garden soil and drinking water. 2. Exogenous
      etiologic factors that are absent from primitive culture of Auyu and Jackai
      tribes in West New Guinea were eliminated. 3. Cycad neurotoxicity has been
      excluded. 4. Suspected exogenous agents that are common in these 3 hyperendemic
      areas are (a) locally grown vegetables, starchy roots, and reef fish; (b) surface
      water containing soluble organic minerals from red laterites; (c) rain water that
      is chemically pure and lack of essential minerals. Pathogenic Speculation:
      Chronic dietary deficiency since birth in Ca, Mg and Zn induced excessive
      absorption of divalent cations which accelerates oxidant-mediated neuronal
      degenerations in a genetically susceptible population. The process is probably
      carried through interactions between cytoskeletal abnormality of the neuron,
      aging process, abnormal proteins, and mitochondrial dysfunction.

PMID- 8752461
TI  - [MR imaging of the brain of amyotrophic lateral sclerosis].
AB  - To investigate imaging characteristics of amyotrophic lateral sclerosis (ALS),
      the author reviewed magnetic resonance (MR) images of the brain of 50 ALS
      patients. MR images demonstrated abnormal foci in the internal capsule in nine
      patients, representing degeneration of the corticospinal tract (CST). These foci
      were hyperintense relative to cortical gray matter on T2-weighted images and
      still hyperintense relative to white matter on proton-density-weighted images. In
      contrast, normal hyperintense foci in the internal capsule representing fibers of
      the CST were isointense to gray matter on T2-weighted images and iso- or
      hypointense to white matter on proton-density-weighted images. T2-weighted images
      showed low signal within the motor cortex in three patients, indicating
      degeneration of the cortex. The images also demonstrated hyperintense lesions in
      the white matter of the precentral gyri in all of them, indicating degeneration
      of the CST. Other studies, however, reported that low signal within the motor
      cortex in aged normal controls was frequently observed. Therefore, the low signal
      was a useful finding only for young ALS patients. T2-weighted images of a patient
      showed hyperintense lesions in the body of the corpus callosum, representing
      degeneration of the commissural fibers interconnecting the motor cortices
      bilaterally.

PMID- 8752462
TI  - [Dysphagia in amyotrophic lateral sclerosis--the mechanism and managements].
AB  - Amyotrophic lateral sclerosis (ALS) raises progressive dysphagia that causes
      aspiration. This diseases affects oral phase first and then pharyngeal phase of
      swallowing. Aspiration pneumonia by dysphagia becomes major problem from clinical
      aspect to cause aggravation of vital prognosis. We explain the mechanism of
      dysphagia from deglutition dynamics and discuss the clinical managements. Several
      functional operations such as cricopharyngeal myotomy, laryngeal suspension and
      so forth, have been applied to prevent aspiration, with satisfactory results in
      cases with mild dysphagia. However, in cases of ALS patients with severe
      aspiration, the results are poor. Then we have to divide airway from digestive
      tract completely to prevent aspiration by laryngectomy. However, the larynx is a
      multi-functional organ, loss of the larynx does improve the swallowing but loose
      phonatory function. We need to evaluate a deglutition function before starting of
      treatments of dysphagia. Besides, we also need to put hopes and life style of
      patients in consideration. We have to be very careful to choose the way of
      surgical treatment and the time of operation. We can conclude that laryngectomy
      is useful for vital prognosis and amelioration of QOL in ALS patients.

PMID- 8752463
TI  - [Reappraisal of amyotrophic lateral sclerosis with dementia].
AB  - Amyotrophic lateral sclerosis (ALS) with dementia is characterized by rapidly
      progressive dementia and motor neuron involvement. The age at onset in 12
      sporadic cases ranged from 43 years to 78 years. The initial symptoms are
      dementia, such as uninhibited behavior and personality change in most patients.
      Both dementia and motor neuron involvement appear within 1 or 2 years of the
      onset. The clinical picture of motor neuron disturbance was bulbar-type ALS. In
      ALS-dementia, lower motor neuron sign is predominant than upper motor neuron
      sign. The pattern of dementia indicated impaired frontal lobe function, confirmed
      by frontal sign such as perseveration, forced grasping and utilization behavior.
      These neurological signs are significant in association with the frontal lesion
      on CT, MRI and single photon emission computed tomography. The pathological
      findings show frontotemporal atrophy, mild non-specific neuronal loss of cortical
      superficial layer, fibrous gliosis of subcortical white matter, degeneration of
      substantia nigra and motor neuron involvement. The clinicopathological findings
      resembled those of dementia of frontal type and are distinct from those of
      Alzheimer's disease. We thus consider that the combination of motor neuron
      disease and dementia is a new clinicopathological entity, quite distinct from ALS
      or other dementias, as Yuasa and Mitsuyama proposed earlier.

PMID- 8752464
TI  - [CT and MRI: what you see and don't see].
AB  - CT and MRI have become indispensable methods for the diagnosis of stroke or the
      investigation for the disease. The use of these auxiliary diagnostic procedures,
      especially of MRI, has made possible the accurate diagnosis of lesions of the
      posterior cranial fossa. The flow void in MRI has made it feasible to infer
      severe stenosis or occlusion of the main arteries before undertaking angiography.
      The silent stroke or white matter abnormalities in the vicinity of the lateral
      ventricle observed in CT or MRI have become a serious clinical problem and these
      are generally considered risk factors for stroke. Obviously, CT and MRI have
      proven effective in this area, yet their findings do not always make it readily
      possible to infer the nature of cerebral arteries involved. Recently, here have
      been attempts to classify infarcts in the region of perforating branches of the
      middle cerebral artery. With the diversification of therapeutic approaches for
      stroke in the days to come, the effort to encourage such insight on the basis of
      non-invasive testing will be increasingly important.

PMID- 8752465
TI  - [MRA].
AB  - With the recent development of MR techniques, it has become possible to obtain
      angiographic images (MRA) of relatively good quality with use of MR. The major
      indications of MRA have been to elucidate the MR findings on spin echo images
      when vascular lesions are suspected and to use MRA for conventional angiography
      when the latter is contra-indicated or additional information is needed. Follow
      up studies of vascular diseases can be easily performed with MRA. The sensitivity
      of this technique for cerebral aneurysms is 73.6%, whereas specificity is 76.2%.
      The sensitivity and specificity for cerebrovascular diseases are 88.7% and 97.4%
      for stenoses of more than 50.0%. Because of rather limited diagnostic accuracy,
      this technique cannot be applied freely for screening of cerebral diseases,
      especially in mass survey for unruptured cerebral aneurysms. There have been many
      new techniques proposed for improvement of spatial resolution of MRA, including
      magnitisation transfer contrast (MTC), tilted optimized non-satulation excitation
      (TONE) and high resolution images. With full development of these new techniques,
      MRA will be used more freely in the diagnosis of vascular diseases.

PMID- 8752466
TI  - [The current role of cerebral angiography in diagnosis of cerebrovascular
      disease].
AB  - The role of cerebral angiography in diagnosis of cerebrovascular disease has
      changed considerably because of the increasing availability of neuroimaging (CT,
      MRI), especially MR angiography (MRA). MRA has almost entirely taken the place of
      cerebral angiography as a screening procedure in evaluation of the cervical
      carotid arteries and main trunks of intracranial arteries. However, detection of
      accurate morphological changes of arterial walls requires cerebral angiography,
      especially in cases of arteritis, arterial dissection and aneurysm of smaller
      than 3 mm in diameter. Cerebral angiography is still needed in order to obtain a
      more precise three dimensional concept of the vascular lesion, esp. in vascular
      malformations, their detailed blood supply, venous drainage and even for a mere
      (but definitive) diagnosis in some cases. Angiography is essential in
      preoperative surgical planning, for evaluation of residual AVM after surgery,
      etc. Technically, intraarterial stereoscopic DSA and serial cerebral angiography
      in stereoscopic magnification are most useful for angiographic diagnosis.
      Intravenous DSA has no advantage over MRA and is therefore no longer a useful
      diagnostic procedure. Cerebral angiography is also useful for evaluation of
      cerebral circulation which is most useful in conjunction with SPECT study.
      Although interventional neuroradiology has made a significant stride in the past,
      it requires further technical improvements and more skillful performance in the
      future.

PMID- 8752467
TI  - [Three dimensional CT angiography using helical scanning].
AB  - Thirty-seven intracranial aneurysms were examined with three dimensional CT
      angiography (3D-CTA) using helical scanning. The raw data were acquired using a
      helical CT scanner (X vigor, Toshiba). The collimation was 1 mm or 2 mm, and the
      table speed was 1 mm or 2 mm/rotation. The contrast medium (iohexol 350) of 1.2
      1.5 ml/body weight kg was intravenously injected at an initial rate of 1.5 ml/sec
      and a second rate of 1.0 ml/sec. The scan delay time was 40-45 sec after the
      injection of the contrast medium. The 3D-CTA was compared with cerebral
      angiography (CAG) in the detectability of aneurysms. The 3D-CTA was equal or
      superior to CAG in 22 aneurysms. The 3D-CTA was less useful in the most aneurysms
      adjacent to the bone such as aneurysms of internal carotid artery. The
      subtraction 3D-CTA was useful in the detection of those aneurysms which could not
      clearly be detected on the 3D-CTA.

PMID- 8752468
TI  - [Diffusion MRI for evaluating cerebrovascular disease].
AB  - There are several new magnetic resonance (MR) technologies, which will provide
      data about the pathogenesis, circulatory state and cellular effects of ischemic
      stroke. Among them, diffusion MRI is the most promising one. This technology
      clearly reveals, within minutes of stroke onset, ischemic lesions which
      ultimately progress to infarct. The early ischemic lesions demonstrated by
      diffusion MRI represent regions with slower water diffusions perhaps due to
      intracellular water accumulation or shrinkage of the extracellular spaces
      resulting from ionic pump failure, spreading depression, or other mechanisms. The
      diffusion MRI can show not only irreversible but also reversible ischemic
      lesions, and therefore has a potential to discriminate salvageable tissues from
      irreversibly damaged tissues before a therapeutic intervention with thrombolytic
      and/or cytoprotective agents. The diffusion MRI can highlight only a fresh
      lesion, because water diffusion is decreased during several days after stroke
      onset. Diffusion MRI is extremely prone to motion artifacts, a major concern
      against clinical application. This problem can be solved by combination with an
      ultrafast technique, echo planar (EP) imaging. The EP diffusion MRI will become a
      rapid, reliable, objective and essential emergency diagnostic test in a clinical
      setting that will guide the development and application of acute therapeutic
      intervention.

PMID- 8752469
TI  - [Positron emission tomography and single photon CT in the diagnosis of
      cerebrovascular disorders].
AB  - The positron emission tomography (PET) and single photon emission CT (SPECT)
      revealed the pathophysiology of ischemic brain in the transaxial images. There
      are several limitations in PET studies by continuous inhalation method using
      oxygen-15 labeled gases. There has been a suspicion about the constancy between
      the red cell volume and plasma volume in the ischemic brain. We measured plasma
      volume by PET using Cu-62 labeled human serum albumin in cases of internal
      carotid artery occlusion. There was no remarkable plasma volume alterations
      between the ischemic and non-ischemic hemisphere. Powers et al demonstrated the
      relationships between the intracranial perfusion pressure changes and vascular or
      metabolic adaptations. The important issue in acute stage of stroke is to
      differentiate the truly alive and completely destroyed tissue. Cerebral blood
      flow change might be affected during acute stage by diaschisis. Recent
      examination using benzodiazepine receptor imaging by SPECT might have a potential
      to depict the damaged tissues, because cortical neuronal cell bodies have a lot
      of the receptors and an ischemic insult induces the loss of the receptors. The
      relationship of crossed cerebellar hypoperfusion (CCH) and supratentorial
      circulatory conditions is attractive, because supratentorial hypometabolism of
      oxygen induced more severe CCH in internal carotid artery occlusion. Therefore,
      we can predict the supratentorial oxygen metabolism by CCH in a case of internal
      artery occlusion. We have a lots of tools to explore the pathophysiological
      states of ischemic brain. These must be dedicated to develop the more effective
      therapeutic procedures.

PMID- 8752470
TI  - [Acetazolamide reactivity on SPECT correlates with PET parameters].

PMID- 8752471
TI  - [Ultrasonic assessment of cerebrovascular disease].
AB  - The aim of this paper of the symposium of the 36th Scientific Meeting of Japanese
      Society of Neurology is to clarify the general status of ultrasonic assessment in
      the imaging modality of cerebrovascular disease (CVD). Although there are many
      ultrasonic techniques, we want to address the carotid ultrasonography and
      transcranial ultrasonography. Cervical carotid atherosclerosis is known to be a
      major cause of brain infarction and Duplex ultrasonography is the best imaging
      tool. This method made it possible to visualize the living human arterial wall
      and to visualize the intraplaque characters. This was most advantage among
      several modalities. Few and really disadvantages of this method are examiner
      dependent results and narrow visual window. On the basis of these ultrasonic
      data, many investigations of nature of stroke have been performed. Transcranial
      ultrasonography have been accepted as a new method for non-invasive intracranial
      vascular imaging. There are the transcranial Doppler, transcranial tomography and
      the transcranial color flow imaging. Using these transcranial methods, we can
      evaluate the intracranial lesions. Transcranial color flow imaging made it
      possible to obtain real images of major arteries of circle of Willis. In
      conclusion, ultrasonic modality is a useful tool for assessing the risk of
      cerebrovascular disease or atherosclerosis, especially in chronic situations.

PMID- 8752472
TI  - [Ultrasound diagnosis of cerebral vascular disease--supplementary presentation
      with special reference to intracranial vessels].
AB  - This study was carried out on patients with chronic cerebral vascular disease
      (CVD) to determine to what extent the intracranial vascular morphology and
      intracranial hemodynamics can be estimated from the common carotid artery blood
      flow (CF) and middle cerebral artery blood flow velocity (MV) determined by the
      ultrasound Doppler method. TCCAD (transcranial Doppler with computer aided
      design) was obtained based on MV information and its clinical implications were
      assessed. CF was 4.88 +/- 0.96 ml/sec for the patients with complete occlusion of
      the internal carotid artery or middle cerebral artery. MV ranged form 40 to 100
      cm/sec and CF was 6.5 ml/sec or more for the majority of patients whose cerebral
      angiographic findings were unremarkable. In patients with complete occlusion of
      the internal carotid artery, however, MV was increased, while CF was decreased.
      It is clear from these results that the MV measurement was taken of blood flow
      increasing contralaterally to the direction of blood flow. Based on TCCAD, the
      vascular course of the middle cerebral artery M1 portion was classified into
      basilar, straight, and dorsal types in CVD patients. The frequency of the dorsal
      type was 0 and the proportion of the basilar type was significantly increased in
      patients under 50 years of age. These findings suggest that cerebral
      arteriosclersis progresses fast in CVD patients under 50.

PMID- 8752473
TI  - [Clinical application of magnetoencephalography for brain infarction].
AB  - Magnetoencephalography (MEG) is a noninvasive functional imaging technique that
      provides information regarding neuronal activity with high spatial resolution.
      Analyses of spikes and slow waves in various brain disorder have performed using
      spontaneous magnetic field, and functional mapping studies have performed using
      evoked magnetic field. The goal of this study was to determine the
      characteristics of MEG findings in these two magnetic fields for ischemic stroke
      patients. In the first examination, we recorded the spontaneous magnetic activity
      with a 37-channel neuromagnetometer and counted the number of equivalent current
      dipoles (neuromagnetic sources) which were divided into 6 groups with different
      frequencies of every 4 Hz. There were much more dipoles below 8 Hz in stroke
      patients than in normal controls, which tended to distribute in the hypoperfusion
      area near the infarct. In the second examination, we recorded auditory evoked
      responses for tone burst stimuli and analyzed the localization of dipoles for the
      100-m.sec. component after the onset of the stimuli. The dipoles lay near the
      Heschl gyrus in most of control group. On the contrary, they often distributed
      apart from the Heschl gyrus in stroke patients with severely damaged regional
      oxygen metabolism measured by positron emission tomography, indicating an
      inappropriate response for auditory stimuli. In conclusion, MEG brought
      interesting informations for the brain function of stroke patients.

PMID- 8752474
TI  - [High-altitude pulmonary edema in Japan].
AB  - To understand the pathophysiology of high-altitude pulmonary edema (HAPE), we
      examined the pathway of adaptation to high altitude in lifelong of Tibet. The
      Tibetan natives had higher exercise performance, but lower maximal oxygen uptake
      and lower blood lactate concentrations than did acclimatized Han newcomers.
      Clinical and basic studies done to determine the pathophysiologic characteristics
      of 47 patients with HAPE and of subjects susceptible to HAPE. The altitude of
      onset was 2,680 m to 3,190 m above sea level. Results of hemodynamic studies and
      the presence of protein-rich edema fluid indicated that HAPE is noncardiogenic
      and is a type of increased permeability edema. The levels of IL-1 beta, IL-6, IL
      8, and TNF-alpha in bronchoalveolar lavage fluid from subjects with HAPE were
      high on admission. The subjects susceptible to HAPE had much greater increases in
      an index of pulmonary vascular resistance than did the controls, which resulted
      in much higher levels of pulmonary arterial pressure during both acute hypoxia
      and hypobaria. The subjects susceptible to HAPE also has blunted hypoxic
      ventilatory drives. We studied whether human leukocyte antigen DR-6 functions as
      a genetic predisposition to HAPE. The frequency of DR-6 was increased in the
      subjects susceptible to HAPE, which suggests that they have a constitutional
      abnormality in the pulmonary circulatory, and ventilatory responses to hypoxia
      and hypobaria, and that genetic factors may be involved in the development of
      HAPE.

PMID- 8752475
TI  - [Prediction of lung cancer deaths and the role of lung cancer screening in
      Japan].
AB  - In Japan, the number of lung cancer deaths has increased continuously since 1950,
      and in 1993 it was the leading cause of cancer deaths in males. This increase has
      been especially noteworthy among older people. In contrast, lung cancer deaths
      have started to decrease in the UK and the US, where anti-smoking activities have
      been strong since the 1970s. Obviously, smoking is the most important risk factor
      for lung cancer. Smoking can explain almost all case of squamous and small cell
      carcinoma. For adenocarcinoma, however, major unknown risk factors remain to be
      defined. Because the effectiveness of lung cancer screening is limited, it is
      necessary to integrate all available methods, including newly developed
      techniques, to prevent lung cancer deaths.

PMID- 8752476
TI  - [Prevention of lung cancer through smoking control activities in Japan].
AB  - Three kinds of smoking cessation programs have been developed by the Osaka Cancer
      Prevention and Detection Center. The first program is "Smoking Quit Contest," in
      which self-help materials are mailed to applicants and prizes are given by lot to
      those who succeed in quitting. The second program is a "Smokebusters" smoking
      cessation program designed for outpatients. The third program is designed for
      people undergoing screening during routine health check-ups, which are widely
      conducted in communities and workplace in Japan. To reduce lung cancer mortality
      in Japan, smoking cessation programs such as those described here should be
      widely implemented and the prevalence of smoking among men in Japan should be
      reduced at least to the levels in the U.S. and in western Europe.

PMID- 8752477
TI  - [Can improvement in therapy decrease the rate of death due to lung cancer?].
AB  - The incidence of lung cancer is increasing, and therapy for patients with this
      disease is not satisfactory. Surgery is done for patients with clinical (c)-stage
      I, II, and resectable stage IIIA non-small cell lung cancer (NSCLC).
      Chemotherapy, alone or in combination with radiotherapy, is given to patients
      with unresectable stage IV and stage III NSCLC, respectively. Chemotherapy is an
      important therapeutic modality for patients with small cell lung cancer (SCLC).
      CDDP + VP-16 (PVP) and CPA + ADM + VCR (CAV) alternating PVP regimens are
      standard treatment for patients with SCLC. Chemotherapy and radiotherapy are
      given to patients with limited disease. To develop more effective treatments, we
      are investigating (1) the schedule and timing of radiotherapy, (2) combination
      chemotherapy including new drugs, (3) dose-intensive chemotherapy, and (4) new
      strategies such as gene therapy. Radiotherapy is commonly used sequentially and
      the standard fractionation is 2 Gy/fr/day. We are studying other timings, such as
      concurrent and alternating, and other schedules, such as hyperfractionation and
      accelerated hyperfractionation. Promising new drugs include paciltaxel,
      docetaxel, vinorelbine, and CPT-11. These are now used in combination with
      platinum. To evaluate dose-intensive chemotherapy for SCLC, we are conducting a
      phase III study comparing CODG + G-CSF with CAV/PVP.

PMID- 8752478
TI  - [Introduction and prospect of peripheral blood stem cell transplantation].
AB  - The number of hematopoietic stem cells circulating in peripheral blood increases
      remarkably during the recovery of marrow function after myelosuppressive
      chemotherapy. In peripheral blood stem cell transplantation, these stem cells are
      collected and cryopreserved, and then used to restore marrow function after
      myelodisruptive (high-dose) anticancer therapy, Marrow recovery is faster with
      this procedure than with autologous bone marrow transplantation. Recently, this
      procedure has been used after high-dose chemotherapy for chemosensitive solid
      tumors such as breast cancer. We used high-dose chemotherapy with etoposide and
      carboplatin, followed by peripheral blood stem cell transplantation, to treat 5
      patients with intrathoracic malignant tumors, including small cell lung cancer
      Neutrophils recovered (> 500 microliters) with 9 to 11 days and platelets
      recovered (> 5,000 microliters) within 8 to 13 days after the transplantation. No
      other serious complication was seen. Current topics regarding this procedure,
      problems to be solved, and prospects for further development are discussed.

PMID- 8752479
TI  - [Molecular approach to lung cancer].
AB  - Lung cancer is associated with a number of cytogenetic abnormalities, such as
      chromosomal deletions on 3p, 12q, and 17p, which suggest the involvement of
      multiple tumor suppressor genes. These findings led to the discovery of the
      inactivation of the Rb and p53 genes in lung cancer. Recent remarkable progress
      in molecular biology should add a number of genes to the list of tumor suppressor
      gene involved in the pathogenesis of lung cancer. In addition, dominant oncogenes
      as well growth factors and their receptors have been shown to be involved in this
      process. Our understanding of the molecular pathogenesis of this fatal disease
      will now allow us to design new strategies to better diagnose and treat lung
      cancer. In this symposium, we discuss how the molecular oncological approach can
      be used to reduce the rapidly increasing rates of death due to lung cancer.

PMID- 8752480
TI  - [Future directions of gene therapy for lung cancer].
AB  - Failure to achieve sustained therapeutic responses with conventional medical
      therapies has presented a challenge to gene therapy as a new approach to lung
      cancer. We used an allo-major histocompatibility complex class I gene (H-2Kb),
      and a gene encoding the thymidine kinase of herpes simplex virus type (HSV1-TK)
      as a drug sensitivity gene. The H-2Kb gene-transfected clones of mouse tumor
      cells were rejected completely by syngeneic DBA/2 mice. Furthermore, the mice
      that had rejected the H-2Kb gene-transfected clone became immune to and rejected
      the parental mouse tumor cells. Transfer of the retroviral vector-mediated HSV1
      TK gene led to ganciclovir-dependent cytotoxicity in human lung cancer cells both
      in vivo and in vitro. Although these findings may lead to gene therapy to control
      lung cancer, further study is needed to determine the proper gene for targeting
      distant tumor cells, and the cell-specific promoter/enhancer sequences that
      regulate the tumor cell-specific expression of the transduced gene.

PMID- 8752481
TI  - [Sign and symptoms in Japanese patients with obstructive sleep apnea: present
      status and problems].
AB  - We studied 176 patients with habitual snoring (HS) and obstructive sleep apnea
      (OSA) to find out whether Japanese patients with OSA differ from those in western
      countries. The prevalence and pathophysiology of hypertension may substantially
      differ between OSA patients in Japan and in western countries: body mass index
      may be more closely associated with hypertension in western patients. No
      statistical relationship was found between obesity and hypertension in Japanese
      patients. Although the reason is unknown, thinner body builds in Japanese
      patients could account for this difference. However, if Japanese patients
      complain of severe obesity or excessive daytime sleepiness, or both, and have a
      saw-tooth sign in the flow-volume curve or hypertension, or both, a
      polysomuography should be indicated.

PMID- 8752482
TI  - [Portable home monitoring system in screening for sleep-disordered breathing].
AB  - Screening for sleep-disordered breathing is often done in an interview and with a
      questionnaire. This method is indirect and it appears to underestimate the
      prevalence of sleep apnea syndrome. Recently, several devices such as the Medilog
      and Vitalog portable monitoring systems were developed. However, these devices
      are difficult for patients to operate by themselves, because they include EEG
      monitoring or measurement of chest and abdominal movement. Therefore, we
      developed a portable monitoring system that is easier to operate. This system can
      be used to assess three variables: oronasal airflow, tracheal sound, and
      electrical activity of the heart. It stores the time of the onset of apnea, apnea
      duration, and R-R intervals with a built-in microcomputer. Apnea episodes, total
      apnea time, mean apnea time, and R-R interval are analyzed with a host computer.
      The sensitivity an specificity of this system are 92.5% and 87.5%, respectively,
      with an apnea index (AI) of less than 10 episodes/h. Using this device, we found
      that the prevalence of sleep apnea syndrome among Japanese industrial workers who
      had an AI of more than 10 episodes was 7.5%. Moreover, from 1984 to 1994 we used
      this device to monitor 1019 outpatients who complained of sleep disturbances such
      as snoring, abnormal breathing during sleep, and excessive daytime sleepiness,
      and found sleep apnea (AI > or = 10) in about 50% of these patients. This
      monitoring system is useful for screening of outpatients with sleep apnea and for
      epidemiological studies of sleep apnea. However, it may be necessary to include a
      non-invasive system for monitoring oxygen saturation in the portable sleep
      monitor, to detect hypoventilation during sleep.

PMID- 8752483
TI  - [How to set up a sleep laboratory in a community general hospital].
AB  - In Japan, sleep-related disorders (SRD) have been handled by only a few
      university teams, and mainly on a research basis, because polysomnography (PSG)
      is labor-intensive, expensive, and unprofitable. Although public consciousness of
      SRDs has been raised by mass-media campaigns, the situation is far from ore that
      would meet patient's demands. We have done 1476 PSG tests over about five years,
      and diagnosed more than 600 cases of SRDs. Therapy included nasal continuous
      positive airway pressure in 170 cases, prosthetic mandibular advancement in 55
      cases, and uvulopalatopharyngoplasty and related operations in 97 cases. We
      describe how we set up a sleep laboratory and a care system, and how to
      circumvent problems. Several points related to the selection of patients for PSG
      in daily clinical practice can be clarified with our data. Computerized sleep
      respiratory analyser might save time and money, but their advantages and
      disadvantages should be studied. The approach to SRDs should be comprehensive and
      systematic, and polysomnographers play an important role. We need programs
      organized by scientific institutions to train polysomnographers. Research should
      continue not only on scientific aspects of SRDs but also on the way patients with
      SRDs are cared for. Reasonable insurance coverage of the costs of nosal
      continuous positive airway pressure and of PSGs is essential for widespread
      access to these services.

PMID- 8752484
TI  - [Current problems in the Diagnosis and stage classification of sleep apnea
      syndrome].
AB  - We examined the relationship between daytime symptoms and respiratory disturbance
      indices during sleep in 60 patients with sleep apnea syndrome who had an apnea
      index of more than 5/hr for at least one night. Daytime hypersomnolence, morning
      headache, and a history of traffic accidents did not correlated strongly with
      apnea index or with nocturnal desaturation. The same was true of daytime blood
      pressure and nocturnal micturition. Both hemoglobin concentration and the mean
      pulmonary arterial pressure in the daytime correlated significantly with indices
      of nocturnal desaturation and not with apnea index, but this might reflect the
      positive correlation between those variables and the base-line level of daytime
      PaO2, in which case it would not be a direct consequence of nocturnal
      desaturation. These data suggest that diagnostic criteria should not be based on
      apnea index or desaturation alone. Long-term follow-up data on Japanese patients
      is needed to establish more rational diagnostic criteria and stage classification
      for sleep apnea syndrome.

PMID- 8752485
TI  - [Non-surgical treatment of obstructive sleep apnea].
AB  - We studied the clinical usefulness of nasal continuous positive airway pressure
      (CPAP) treatment of obstructive sleep apnea syndrome (OSAS). The subject were 56
      men with OSAS. Their mean age, apnea index, and SaO2 were 51 +/- 8 years, 48 +/-
      18, and SaO2 were 51 +/- 8 years, 48 +/- 18, and 81 +/- 7%, respectively. After
      titration of CPAP, they underwent nasal CPAP treatment at home every night.
      Symptoms, blood pressure, pulmonary function, compliance with the prescription
      and complications of treatment were evaluated every one or two months in an
      outpatient clinic. Blood pressure decreased significantly from 135 +/- 15 mmHg
      (systolic) and 88 +/- 14 mmHg (diastolic) to 126 +/- mmHg (systolic) and 78 +/- 6
      mmHg (diastolic) in 51 cases after two weeks of treatment. No significant change
      in pulmonary function except for blood gases was observed after longterm
      treatment. Excessive daytime sleepiness disappeared and sleep quality improved
      after treatment in most cases. Thirty-six of 43 patients continued to use nasal
      CPAP for 34 +/- 16 months and 33% complied with the prescription. Although nasal
      mask discomfort and dryness of the nose and mouth occurred in several cases,
      there were no serious complications. These findings suggest that nasal CPAP is
      useful for treatment of patients with OSAS. However, the problem remains that the
      cost of nasal CPAP is not reimbursed by the public health insurance system in
      Japan.

PMID- 8752486
TI  - [Surgical treatment of obstructive sleep apnea and snoring].
AB  - Over the past three years, surgery was performed on 149 patients (55 children and
      94 adults) who complained of snoring and symptoms related to sleep apnea
      syndrome, at Fujita Health University's Second Hospital. Treatment in children
      was adeno-tonsillectomy. Treatment in adults was uvulo-palato-pharyngoplasty, and
      midline laser grossectomy or nasal surgery, or both. The apnea hypopnea index was
      (AHI) was defined as the frequency of apneic and hypopneic events per hour.
      Pathological apnea (sleep apnea syndrome) was defined as an AHI of 10 in adults
      and an AHI of 5 in children. Marked improvement was defined as a 75% reduction in
      AHI or a postoperative AHI below 10 in adults and below 5 in children.
      Improvement was defined as a 50% to 74% reduction in AHI. Slight improvement was
      defined as a 29% to 49% reduction in AHI. No improvement was defined as a
      reduction in AHI of less than 25%. Of the 55 children, the AHI in 35 was above
      5:30 (86%) improved markedly with the treatment; 3 (8%) improved; 1 (3%) improved
      slightly, and 1 (3%) did not improve. Of the 94 adults, the AHI in 84 was above
      10:40 (48%) improved markedly with the treatment; 12 (14%) improved; 14 (17%)
      improved slightly and 18 (21%) did not improve.

PMID- 8752487
TI  - [Treatment of obstructive sleep apnea syndrome with a mandibular positioning
      device and other nonsurgical modalities].
AB  - The therapeutic approach to a patient with obstructive sleep apnea syndrome
      (OSAS) must be individualized because of the heterogeneity in the pathogenesis of
      the disorder. Although nasal continuous positive airway pressure (CPAP) is
      effective no matter what the pathogenesis, risk factors for this disorder should
      be identified in each patient. Nasal CPAP will be discussed by others. Weight
      loss is one of the best nonsurgical treatments of OSAS and it should be strongly
      recommended to obese patients with the disorder, even though only a few achieve
      satisfactory weight reduction. Sleeping in the lateral position or upright may be
      effective in some patients with OSAS. Acetazolamide, medroxyprogesterone, or
      protriptyline may also have a role in some patients, although the efficacy must
      be weighed against the considerable side effects. The cross-sectional area of the
      oropharynx measured by computed tomography in patients with OSAS was
      significantly lower than that in control subjects. Lateral cephalograms revealed
      a retarded mandible in many patients. A dental device designed to advance the
      mandible 2 to 7 mm and to eliminate the airway obstruction at the base of tongue
      was used in 20 consecutive patients (17 men and 3 women, average age 53.8 years)
      to treat the obstructive sleep apnea. The body mass index of the patients was
      27.6 +/- 4.2 kg/m2 (mean +/- SD). The device moved the mandible forward (p =
      0.038) and increased the airway space in the lower part of the oropharynx (p =
      0.031) as assessed with lateral cephalograms. After nightly use of the device for
      24 to 211 days, overnight polysomnography was performed for two nights: without
      the device for the first night and with it for the second night. The apnea index
      was reduced from an average of 30.7 to 18.5 events/hour (60.4% of the
      pretreatment value, p = 0.004). The number of desaturations (more than 5%
      decrease from the base line SaO2) decreased and the lowest level of SaO2
      increased: from 26.5 to 14.4 events/hour (p = 0.009) and from 63.6 to 70.1% (p =
      0.005), respectively. Not every patient improved sufficiently. Eleven of 20
      patients were classified as good responders, because of a reduction in apnea
      index of at least 50% of the pretreatment value, and the remaining nine patients
      were classified as poor responders. Use of the device reduced the severity
      ratings of snoring and excessive daytime sleepiness not only in the good
      responders but also in the poor responders. No serious complications were
      observed. The mandibular positioning device is an effective treatment for some
      patients with OSAS. The effectiveness of the device should be predicted from
      polysomnographic and cephalometric data, and from CT measurements of the upper
      airway and other characteristics of the patients.

PMID- 8752488
TI  - [Diagnosis and treatment of sleep apnea syndrome in Japan --comparison with other
      countries].
AB  - The prevalence of sleep apnea syndrome (SAS) in Japan has been reported to be
      about 1-2%, which is almost the same as that reported in western countries.
      However, an epidermiological survey of SAS recently performed by institutes
      participating in the Japanese Society of Sleep-Disordered Breathing showed that
      only 1,425 patients were newly diagnosed in 1993, which suggests that there are
      many latent or undiagnosed cases in Japan, because SAS is newly diagnosed in
      75,000 patients every year in the USA. Here we reported on issues related to the
      diagnosis and treatment of SAS in Japan and in other countries.

PMID- 8752489
TI  - [A new system for classifying bronchial asthma].
AB  - Classification of bronchial asthma with Rackemann's system or Swineford's system
      is too simple to be clinically useful. We developed a new system for classifying
      patients with asthma. Patients were assigned a "0" or a "1" for each of five
      criteria: the presence or absence of (1) steroid dependence, (2) allergy, and (3)
      sensitivity to aspirin, and whether or not their asthma was judged to be (4)
      hereditary and (5) infectious. For example, patients who were sensitive to
      aspirin and whose asthma was judged to be of the infectious type were classified
      as 00101. A total of 434 patients with asthma were studied (185 males and 249
      females, ranging in age from 10 to 93 years). The patients were classified into
      32 subtypes (shown in an accompanying table), and the data were compared to the
      results of classification by other methods. The present system may be more useful
      than those of Rackeman or Swineford, because it takes heredity and sensitivity to
      aspirin into account. A total of 103 patients could not be classified by
      Swineford's system: those in classes 00000, 00010, 00100, 00110, 10000, 10010,
      10100, and 10110. We expect this new system for classifying bronchial asthma to
      be clinically useful.

PMID- 8752490
TI  - [Classification of asthma based on genetics].
AB  - Genetic factors may contribute to the development of bronchial asthma. However,
      results of traditional epidemiological studies have not clarified exactly which
      genes are involved. Recent advances in molecular genetics have resulted in the
      discovery of some candidate genes. Although there is still only a little
      information about the role of these genes in the development of asthma, we
      attempted to classify asthma based on genetics and here we present one example of
      such a classification. Classification of asthma based on genetics may be useful
      in screening for people susceptible to asthma and in developing prophylactic
      procedures. It may also enhance our understanding of the mechanisms of asthma and
      may promote the development of new therapeutic strategies.

PMID- 8752491
TI  - [Classification of bronchial asthma based on immunological mechanisms].
AB  - A classification of bronchial asthma based on immunological mechanisms is
      proposed. For this classification, asthma was divided into antigen-dependent and
      antigen-independent types. Antigen-dependent asthma was classified into antibody
      dependent and antibody-independent sub-types. Antibody-dependent asthma was
      further subdivided into IgE-mediated, IgG-mediated, immune complex-mediated, and
      complement-mediated sub-types. Diisocyanate asthma was considered to be an
      example of antibody-independent asthma. Exercise-induced asthma and drug-induced
      asthma, such as aspirin-induced asthma, were included in the sub-type of antigen
      independent asthma.

PMID- 8752492
TI  - [Classification for bronchial asthma from the viewpoint of autonomic nerve
      function and airway hyperreactivity].
AB  - In the present study, patients with asthma ware evaluated in order to find out if
      the emotional stress itself causes their asthmatic attack or not, and to
      elucidate the mechanisms underlining it. 41.8% of the 55 patients demonstrated
      asthmatic attack during hypnosis evaluated their symptoms and significant
      decrease in their air flow. The non-responders showed significant increase ind
      the serum DBH level (p < 0.05) during the hypnosis compared with their baseline
      value, while the responders did not show any significant change in the serum
      concentration. However, the responders shows significant increase in serum
      histamine concentration during (p < 0.01) and 40 min (p < 0.05) after the
      hypnosis. These data suggest that the increased sympathetic nerve activity during
      the hypnosis suppresses the release of chemical mediators from inflammatory cells
      and autonomic nerve terminals in the airways.

PMID- 8752493
TI  - [Aspirin-induced asthma as an important type of bronchial asthma].
AB  - Aspirin-induced asthma (AIA) should be recognized as an important types of
      bronchial asthma for the following reasons. 1) The pathogenesis of AIA is
      specific. Inhibition of cyclooxygenase a (key enzyme for the production of
      prostanoids from arachidonic acid) by non-steroidal antiinflammatory drugs
      (NSAID) is an important trigger of asthma attacks. 2) The frequency of AIA is not
      low. It is estimated to be 9.8% in adults with chronic asthma. 3) Some clinical
      features of AIA are characteristic. Naso-sinus complications, such as rhinitis,
      chronic sinusitis, nasal polyposis, and anosmia, are commonly found in patients
      with AIA. 4) Glucocorticoids with succinate ester, which are commonly used to
      treat asthma attacks, induce asthma symptoms or provoke severe asthma attacks in
      70% to 80% of patients with AIA. 5) Some patients with AIA are hypersensitive to
      some agents in addition to NSAID, e.g., tartrazine (15.1%), sodium benzoate
      (14.3%), and parabens (12.0%). 6) Patients with latent AIA are in danger of
      having fatal or near-fatal asthma attacks if they take NSAID. We should educate
      patients to eliminate the risk posed by NSAID and other agents that may induce
      asthma attacks, and should enlighten doctors and pharmacists, who are not
      specialists in allergy or respiratory disease, about AIA. 7) Asthma in these
      patients will be less severe if their condition is correctly diagnosed and they
      receive appropriate medical treatment.

PMID- 8752494
TI  - [Involvement of G proteins between receptors and KCa channels in the regulation
      of airway tone by the autonomic nervous system].
AB  - The mechanical tone of the airways is regulated by the autonomic nervous system,
      partly via the activity of ion channels. Ca(2+)-activated K+ (KCa) channels are
      densely distributed on tracheal smooth muscle cells. We found that beta
      adrenergic agonists can augment KCa channel activity via the alpha subunit of the
      stimulatory GTP-binding (G) protein of adenylyl cyclase, Gs, linked with beta
      receptors, and that muscarinic agonists can suppress the activity of this channel
      via the inhibitory G protein of adenylyl cyclase (pertussis toxin-sensitive G
      protein), Gi, linked with muscarinic receptors. These results show that there is
      a dual regulation system of KCa channels, which involves stimulation of the two
      receptors. Records of isometric tension from guinea pig tracheas incubated with
      pertussis toxin and cholera toxin show that regulation of KCa channels mediated
      by Gi and Gs may be important in the mechanical antagonism by the two receptor
      agonists, and they show that G proteins coupling between receptors and KCa
      channels may be important in beta-adrenergic bronchodilation in the treatment of
      asthma. In a previous study in eight atopic asthmatic patients, pretreatment with
      a beta-agonist abolished allergen-induced bronchoconstriction with no increment
      in mean plasma histamine, results that are similar to those obtained with
      cromyolyn sodium, a membrane stabilizer. The membrane-delimited reaction may be a
      key process in the autonomic regulation of airway tone. In immediate asthmatic
      reactions (IAR), histamine release from mast cells, contraction of airway smooth
      muscle, and transmitter release from post-ganglionic neurons within
      parasympathetic ganglia are believed to be caused by membrane hypopolarization.
      Because activation of KCa channels leads to hyperpolarization, beta-agonists that
      cause membrane hyperpolarization (short acting beta-agonists) may antagonize IAR
      at the level of the cell membrane. In late asthmatic reactions (LAR), short
      acting beta-agonists do not have marked effects. However, recent reports have
      indicated that long-acting beta-agonists that do not cause hyperpolarization can
      inhibit LAR. Cromakalim, an ATP-sensitive K+ channel activator, reduces the
      "morning dip" when it is given orally to patients with nocturnal asthma. These
      findings show that activation of K+ channels may be useful in therapy of
      bronchial asthma.

PMID- 8752495
TI  - [Classification of asthma according to etiology, pathophysiology, and treatment:
      effects of antiallergic drugs].
AB  - Selective inhibitors of mediators are among recently developed antiallegic drugs.
      Studies of the effects of these inhibitors on different types of asthmatic
      reactions can clarify the heterogeneity of asthma. Heterogeneity may be found
      both among patients and among types of asthmatic reactions. Although the
      differences among patients with regard to mediators of spontaneous asthma attacks
      is still unclear, the differences among asthmatic reactions induced by some well
      defined stimuli are known. For example, leukotrienes are dominant in asthmatic
      reactions induced by analgesics, and histamine is dominant in bronchoconstriction
      induced by alcohol. Types of asthma may be classified according to the main
      contributing mediator.

PMID- 8752496
TI  - [Classification of bronchial asthma according to steroid and immunosuppressive
      treatment].
AB  - In long-term management of bronchial asthma, severity is classified according to
      the need for steroid treatment. In mild asthma, no chronic steroid treatment is
      needed; bronchodilators alone can relieve symptoms. In patients with moderate
      asthma, continuous inhaled steroids are necessary. In severe asthma, both oral
      and inhaled steroids are necessary. Patients resistant to steroids are included
      among those with severe asthma. Patients who need 10 mg or more of prednisolone
      per day to control their asthma are classified as steroid resistant. However,
      steroid resistance has also been defined in terms of the reversibility of the
      forced expiratory volume 1 second (FEV1) after 1 to 2 weeks of oral steroids. The
      mechanism of steroid resistance remains to be clarified; functional derangement
      and a reduction in the number of steroid receptors on lymphocytes have been
      postulated as mechanisms. Turner-Warwick classified asthmatics according to the
      way that peak flow is affected by therapy. In her classification, patients with
      "brittle" asthma are likely to be steroid resistant and those with "irreversible"
      asthma are likely to be steroid resistant and those with "irreversible" asthma
      are likely to be steroid dependent. This classification implies that response to
      steroid therapy may be predicted from measurements of peak expiratory flow.
      Therefore, although the response to steroid therapy may not be useful in
      classifying the pathogenesis of asthma, it is one of the most important ways to
      classify the severity of asthma.

PMID- 8752497
TI  - [Evaluation of a respiratory care unit on a 45-bed hospital ward].
AB  - With a limited number of beds for patients undergoing medical and surgical
      treatment for respiratory diseases, we set aside 6 of 45 beds on one floor to be
      used as a respiratory care unit. During the past 5 years, 1820 patients (1225
      medical and 595 surgical) were admitted to the respiratory care unit; they were
      treated for an average of 5.02 days. Of the patients being treated medically, 451
      received mechanical ventilatory support. The majority of those patients had acute
      exacerbations of chronic respiratory failure due to emphysema or to sequelae of
      pulmonary tuberculosis. Acute respiratory distress associated with asthma or with
      pneumonia were also relatively common, as was the adult respiratory distress
      syndrome. A total of 119 patients on home oxygen therapy are being seen as out
      patients, and the respiratory care unit was found to be quite useful whenever
      they needed intensive management. Only 148 (8.1%) of the patients admitted to the
      respiratory care unit died before discharge, and the ratio of cost to performance
      was good. The respiratory care unit was most effective in allowing for continuity
      of care from the onset of respiratory distress, and including exacerbations,
      surgical interventions, postoperative management, and out-patient care.

PMID- 8752498
TI  - [Bronchoscopy in the diagnosis of diffuse pulmonary infiltrates, and
      corticosteroid treatment in patients with acute respiratory failure].
AB  - Forty patients with acute respiratory failure underwent fiberoptic bronchoscopy
      for evaluation of diffuse pulmonary infiltrates. Immunohematological diseases
      were the commonest underlying conditions; they were present in 48% of patients.
      Twenty-five percent of patients had pulmonary disease. Fiberoptic bronchoscopy
      was done 2.2 days after confirmation of the pulmonary lesion. Seventy-three
      percent of patients had already received antibiotics and 28% required mechanical
      ventilation at the time of fiberoptic bronchoscopy. Arterial blood gas analysis
      done just before fiberoptic bronchoscopy revealed that PaO2 and PaCO2 were 62
      Torr and 36 Torr, respectively. A specific diagnosis was made in 29 patients
      (73%): pneumonia in 13; pulmonary fibrosis in 4; summer-type hypersensitivity
      pneumonitis in 3; and leukemic cell infiltration in 2. Fifty-two percent of
      patients were successfully treated with specific therapy. The complications of
      fiberoptic bronchoscopy were bleeding in 3 patients, pneumothorax in 3 patients,
      and exacerbation of respiratory failure in one patient. There were no procedure
      related deaths, and fiberoptic bronchoscopy was judged to be safe and useful in
      the diagnosis of pulmonary infiltrates in patients with acute respiratory
      failure. Twenty-five patients (68%) received high doses of methylprednisolone.
      The average initial dose was 851 +/- 373 mg, and more than 100 mg was
      administered for 8 +/- 6 days. Seventeen of these patients recovered from the
      pulmonary disease. A controlled randomized study is needed to reevaluate the role
      of corticosteroids in the treatment of acute respiratory distress syndrome.

PMID- 8752499
TI  - [Non-invasive evaluation of pulmonary hemodynamics by pulsed Doppler
      echocardiography in patients with chronic obstructive pulmonary disease].
AB  - Pulsed doppler echocardiography is reported to be a reliable method for
      evaluating pulmonary hemodynamics in patients with cardiovascular diseases, but
      not with chronic obstructive pulmonary disease (COPD) because of the difficulty
      in obtaining an appropriate echo-window in such patients. We examined 23 patients
      with COPD by doppler echocardiography (Hewlett-Packard, HP77020CV) with a 2.5 MHz
      transducer via the subcostal approach in a supine position. The right side of the
      heart catheterization was performed simultaneously in sixteen of these patients.
      The remaining 7 patients received the same procedure within one week of the
      doppler echocardiography. Adequate ejection flow pattern from the right ventricle
      was obtained in all the patients. Significant negative linear relationships were
      found between pulmonary arterial pressure and acceleration time (r = -0.67) and
      ejection time (r = -0.52). These findings show that doppler echocardiography can
      be useful when evaluating pulmonary hemodynamics even in patients with COPD.

PMID- 8752500
TI  - [Mechanical ventilation and long-term respiratory care in the intensive care unit
      of a general hospital].
AB  - We studied the need for mechanical ventilation in 265 patients with respiratory
      failure who came to our medical ICU over the past 3 years. The time required for
      weaning from mechanical ventilation and the percentage of patients who needed
      oxygen therapy or mechanical ventilation at home after their condition was no
      longer acute were also studied. Of the patients treated in the medical ICU, 143
      (54%) required mechanical ventilation; 104 (39%) had acute respiratory failure
      and the others had acute exacerbations of chronic respiratory failure. Some
      causes of acute respiratory failure were aspiration pneumonia, bronchial asthma,
      and drug use. Three-fourths of those with chronic respiratory failure had
      pulmonary emphysema, sequela of pulmonary tuberculosis, or idiopathic
      interstitial pneumonia. In patients with chronic respiratory failure, success in
      weaning could be predicted from the respiratory index (PaO2/FIO2), the serum
      albumin level, and the length of time that they were ventilated with more than
      60% oxygen. Thirteen patients with chronic respiratory failure died while
      receiving mechanical ventilation. Of those who survived, 11 underwent
      tracheostomies, and 4 of those 11 were mechanically ventilated at home with
      portable devices. Ten other survivors received home oxygen therapy. Chest
      physicians bear the greatest responsibility for managing mechanical ventilation
      in medical emergencies. Moreover, the prognosis for patients with chronic
      respiratory failure can be improved with a long-term program for respiratory care
      that includes home mechanical ventilation and home oxygen therapy.

PMID- 8752501
TI  - [Long-term mechanical ventilation in Japan, with special reference to home
      mechanical ventilation].
AB  - Some patients in respiratory care units are difficult to wean from mechanical
      ventilation, and may be candidates for home mechanical ventilation (HMV). HMV may
      improve these patients' quality of life and decrease medical expenses. Since
      1987, six nationwide questionnaire surveys were done to study the status of long
      term mechanical ventilation (defined as mechanical ventilation for at least 90
      days) and HMV in Japan. In 1994, an additional questionnaire regarding opinions
      about HMV was sent to physicians, patients undergoing HMV, their families, and
      people in companies that deal with home ventilators. From 1987 to 1994, the
      number of patients who had been mechanically ventilated for at least 90 days
      increased from 368 to 956. According to the 1994 survey, 565 of those patients
      were not candidates for HMV, 235 of them were candidates for HMV but could not be
      shifted (reasons are given below), and 156 were shifted to HMV. The reasons that
      some patients who were considered to be candidates for HMV could not be shifted
      included a lack of caregivers at home (58.1%), the cost of a ventilator (44.5%),
      lack of proper health insurance (39.8%), problems with ventilator maintenance and
      delays in obtaining repairs (37.7%), and inadequacies in the system for providing
      medical care in the home (33.1%). Despite the problems entailed in shifting to
      HMV, many patients undergoing HMV (77.8%) and members of their families (83.3%)
      expressed a desire to continue this therapy. Many physicians (94.0%) said they
      believed that HMV improves the quality of life of patients with chronic
      respiratory failure. Some companies intend to begin renting ventilators for HMV.
      The use and development of HMV in Japan would be promoted if the national health
      insurance covered the costs of this therapy.

PMID- 8752502
TI  - [Inhibitory non-adrenergic, non-cholinergic nerves and nitric oxide].
AB  - We studied the role of nitric oxide and inhibitory non-adrenergic, non
      cholinergic (i-NANC) nerves in the regulation of airway responsiveness in
      anesthetized and mechanically ventilated cats. Vagal stimulation caused marked
      bronchodilation in the cats with sustained bronchoconstriction in the presence of
      atropine and propranolol. The bronchodilation evoked by vagal stimulation was
      completely abolished by hexamethonium (2 mg/kg). L-NG-nitroarginine methyl ester
      (L-NAME; 8 mg/kg + 2 mg/kg/min) significantly suppressed the relaxation evoked by
      vagal stimulation; the effect was particularly noticeable soon after the
      stimulation. Hexamethonium significantly increased airway responsiveness to
      serotonin: the PC200 decreased from 0.346 mg/ml (GSEM 1.23) without hexamethonium
      to 0.44 mg/ml (GSEM 1.63) with hexamethonium (p < 0.05). L-NAME shifted the dose
      response curve to serotonin significantly to the left: the PC200 decreased from
      0.261 mg/ml (GSEM 1.,40) without L-NAME to 0.056mg/dl (GSEM 1.38) with L-NAME (p
      < 0.05). Inhalation of citric acid (20%) caused marked bronchodilation during
      serotonin-induced bronchoconstriction. This bronchodilation occurred in the
      presence of atropine and propranolol and was inhibited by hexamethonium,
      therefore it was probably caused by a reflex mediated by i-NANC nerves.
      Furthermore, the bronchodilation induced by i-NANC nerves was significantly
      suppressed by L-NAME. These results suggest that nitric oxide is an important i
      NANC transmitter that can modulate airway responsiveness.

PMID- 8752503
TI  - [Nitric oxide synthase in lung epithelial cells in culture].
AB  - To identify the molecular nature of nitric oxide synthase (NOS) and its
      regulation and function in the airway, NOS activity and NOS mRNA expression were
      measured in cultured lung epithelial cell. All epithelial cells exhibited
      constitutive NOS activity that was calcium-dependent, and inducible, lesser
      calcium-dependent activity in the presence of interferon-gamma, interleukin-1
      beta, tumor necrosis factor-alpha, and lipopolysaccharide. Two distinct NOS mRNA
      species (neuronal and inducible) were found with the reverse transcription
      polymerase chain reaction. The co-existence of constitutive and inducible NOS in
      human alveolar and bronchial epithelial cells indicates that nitric oxide may
      have many roles in normal and diseased lungs.

PMID- 8752504
TI  - [Effect of endogenous and inhaled nitric oxide on pulmonary microcirculation].
AB  - The sites of action of endogenous and inhaled nitric oxide (NO) were reassured
      during hypoxic pulmonary vasoconstriction. Lungs of 21 adult cats were perfused
      in situ with autologous blood in zone-3 conditions. Capillary pressures were
      measured by the double-occlusion techniques and pressures in arterioles and
      venules 70-100 microns in diameter were measured by the servo-null micropuncture
      technique, both during normoxia (FiO2 = 0.3) and during hypoxia (FiO2 = 0.02).
      The effects of NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), an inhibitor
      of NO synthase, and of inhaled NO (5-100 ppm) were also measured. The PO2 of the
      prefusate decreased from 187.6 +/- 5.3 mmHg during normoxia to 25.7 +/- 1.3 mmHg
      during hypoxia, and further decreased to 20.8 +/- 2.2 mmHg during hypoxia with 50
      ppm NO (p < 0.05, compared with hypoxia only). Increases in pulmonary vascular
      pressure drop in response to hypoxia were 4.8 +/- 1.0 cmH2O and 9.1 +/- 1.4 cmH2O
      in non-treated and L-NAME-treated lungs, respectively (p < 0.05). L-NAME
      significantly increased hypoxic construction in the venous segment. The
      concentration of exhaled NO increased from 13 +/- 4 ppb during normoxia to 18 +/-
      4 ppb during hypoxia (p < 0.1). Inhaled NO lowered not only pulmonary artery
      pressure but also capillary pressure in a dose-dependent manner, which reduced
      hypoxic pulmonary vasoconstriction. Pulmonary veins were more sensitive to
      inhaled NO than were arteries. Inhaled NO (50 ppm) dilated vessels smaller than
      70 to 100 microns in diameter, by 39% (p < 0.05), and dilated venules greater
      than 100 microns in diameter by 26% (p < 0.05), but did not significantly dilate
      arterioles greater than 100 microns in diameter (11%). Inhaled NO did not
      significantly change the ratio of wet weight to dry weight. We conclude that both
      endogenous and inhaled NO attenuate hypoxic pulmonary vasoconstriction, with
      significant pulmonary venous dilation. The main site of action of inhaled NO is
      vessels smaller than 100 microns in diameter and venules greater than 100 microns
      in diameter. Inhaled NO (5-100 ppm) does not cause interstitial edema.

PMID- 8752505
TI  - [Increased production of nitric oxide in the immediate and late asthmatic
      responses in models of guinea pig experimental asthma].
AB  - Nitric oxide is produced in mammalian airways by constitutive and inducible
      nitric oxide synthase, and endogenous nitric oxide can be detected as exhaled
      gas. Patients with asthma have large numbers of airway epithelial cells and
      inflammatory cells that contain nitric oxide synthase, and nitric oxide levels in
      exhaled air are high during immediate asthmatic responses. To examine the
      dynamics of nitric oxide synthase in the tracheas of guinea pigs, cumulative dose
      response studies of 5-HT were done on tracheal strips, in the presence or absence
      of arginine and its analogues. This assay indicated that relative the activity of
      nitric oxide synthase was greater 6 hr after the challenge than immediately
      after, which suggests that nitric oxide is involved in the pathogenesis of
      bronchial asthma attacks.

PMID- 8752506
TI  - [Basic evaluation of nitric oxide inhalation therapy].
AB  - We studied the site of action of nitric oxide (NO) and the dose-response
      relationship between inhaled NO and PaO2. We also measured nitrosyl-hemoglobin
      (Hb-NO) levels in arterial and mixed venous blood and NO2 levels in our NO
      inhalation system to confirm the safety of NO inhalation. In an ovine model of
      ARDS induced by lung lavage, pressure-flow plots indicated that the site of
      action of inhaled NO was close to the alveoli. During hypoxia, pulmonary artery
      pressure decreased as the concentration of inhaled NO increased; PaO2 peaked at
      10-20 ppm NO. The levels of Hb-NO in arterial and mixed venous blood during
      inhalation of 40-60 ppm NO under hypoxic conditions were greater than the levels
      under normoxic conditions, but Hb-NO still accounted for less than 0.1% of the
      total Hb. Less than 0.1 ppm on NO2 was generated during inhalation of 5 ppm NO.
      In conclusion, inhaled NO can dilate pulmonary vessels near alveoli without
      lowering the O2 carrying capacity of blood. In the present system, only a
      negligible amount of NO2 was produced.

PMID- 8752507
TI  - Current status of nitric oxide inhalation.
AB  - Nitric oxide (NO) is an important endothelium-dependent relaxing factor. In some
      pulmonary hypertensive states such as ARDS, the production of endogenous NO may
      be impaired. Nitric oxide inhalation selectively dilates the pulmonary
      circulation. Significant systemic vasodilation does not occur because NO is
      inactivated by rapidly binding to hemoglobin. In an injured lung with pulmonary
      hypertension, inhaled NO produces local vasodilation of well-ventilated lung
      units and may "steal" blood flow away form unventilated regions. This reduces
      intrapulmonary shunting and may improve systemic arterial oxygenation. Several
      observations require further study: 1. The hemodynamic and respiratory effects of
      NO inhalation vary, both among patients and within the same patient over the
      course of an illness. 2. Occasionally, sudden discontinuation of inhaled NO
      produces problematic pulmonary vasoconstriction. 3. NO inhalation may affect
      pulmonary structure and function and endogenous NO synthesis and transduction.
      Inhaled nitric oxide may have both beneficial and detrimental effects. 4. The
      safety and clinical efficacy of long-term NO administration remain unclear.
      Several randomized prospective clinical trials are beginning to address these
      issues. Potentially, inhaled NO may be a valuable therapy in a wide variety of
      patients with pulmonary hypertension and/or lung injury.

PMID- 8752508
TI  - [Airway epithelium and nitric oxide].
AB  - To measure the generation of nitric oxide (NO) by airway epithelial cells and to
      study the physiological role of NO in the regulation of epithelial functions, we
      studied ciliary motility of rabbit cultured tracheal epithelium in vitro and ion
      transport across tracheal mucosa in vivo. Isoproterenol dose-dependently
      increased ciliary beat frequency, as measured by photoelectric methods. Perfusion
      of tracheal mucosa with tachykinins increased the diffusion potential for
      chloride ions, as measured in the presence of amiloride under open-circuit
      conditions: the rank order of potency was neurokinin A > substance P >>
      neurokinin B. These responses to isoproterenol and to tachykinins were attenuated
      by pretreatment with NG-nitro-L-arginine methylester, and this attenuation was
      reversed by L-arginine. In contrast, NG-nitro-D-arginine methylester and D
      arginine had no such effects. NO concentrations in the medium and perfusate were
      measured in realtime with an amperometric sensor specific to this molecule, and
      immersion of the electrode allowed detections of a polarographic current under
      unstimulated conditions. Addition of isoproterenol, neurokinin A, or substance P
      caused a rapid and dose-dependent increase in NO concentration. Histochemical
      examination for NADPH diaphorase activity in cultured epithelium showed strong
      staining within the cytoplasm. These results suggest that NO is spontaneously
      released from airway epithelial cells and that generation of this molecule may
      contribute to airway epithelial ciliary motility and chloride ion secretion
      mediated by beta-adrenoceptors and by tachyinin NK2 receptors.

PMID- 8752509
TI  - [Role of nitric oxide in asthma-like symptoms induced by diesel exhaust particles
      in mice].
AB  - Asthma-like symptoms were induced in mice by repeated intratracheal instillation
      of diesel exhaust particles. Nitric oxide synthase (NOS) and superoxide dismutase
      (SOD) in airways were studied with immunocytochemical methods, and the role of
      nitric oxide was examined with the NOS inhibitor L-NMMA. Diesel exhaust particles
      increased the staining of cNOS in airway epithelial cells by an anti-cNOS
      antibody. Macrophages in the mucous membrane were stained clearly, but an anti
      iNOS antibody did not stain airway epithelial cells. Diesel exhaust particles
      caused a 4-fold increase in the total number of macrophages, neutrophils,
      eosinophils, and lymphocytes in bronchoalveolar lavage fluid. Diesel exhaust
      particles decreased the staining of Cu, Zn-SOD, and Mn-SOD in epithelial cells by
      their respective anti-SOD antibodies. Diesel exhaust particles doubled the
      concentration of nitric oxide in exhaled air. These particles increased
      respiratory resistance, and this increase was suppressed by pretreatment with the
      NOS inhibitor L-NMMA. These results suggest that diesel exhaust particles can
      decrease the scavenging of O2- in airways, which may increase
      hyperresponsiveness. In mice exposed to diesel exhaust particles, the increase in
      NOS staining in airway epithelium, the increase in the nitric oxide concentration
      in exhaled air, and the decrease in respiratory resistance caused by L-NMMA
      indicate that nitric oxide may increase airway hyperresponsiveness.

PMID- 8752510
TI  - [Lung injury and pulmonary vascular endothelial cell injury].
AB  - Pulmonary vascular endothelial cells are an important barrier that helps keep
      lung tissue intact. These cells are exposed to potentially injurious cells and to
      harmful mediators that are produced in or released into the blood. The
      endothelial cells may then be stimulated and injured. Stimulated and injured
      pulmonary vascular endothelial cells can themselves produce and release injury
      promoting mediators. Using isolated perfused rat lungs and cultured human
      pulmonary endothelial cells, we assessed the effect of neutrophil-derived
      injurious mediators, leukotoxin, and neutrophil elastase on the pulmonary
      endothelium. Both mediators caused high-permeability pulmonary edema in the
      isolated lungs and caused dose-dependent and time-dependent damage in the cell
      cultures. Injury due to leukotoxin was suppressed in the presence of LNMMA or
      superoxide dismutase and injury due to neutrophil elastase was suppressed by
      neutrophil elastase inhibitors. These data indicate that these mediators cause
      lung injury via different mechanisms and that they may synergistically evoke
      clinical lung injury.

PMID- 8752511
TI  - [The role of interstitial hyaluronan in acute lung injury].
AB  - The pulmonary interstitium may affect the movement of water, macromolecules, and
      inflammatory cells between capillaries and lymphatics. Hyaluronan (hyaluronic
      acid), a glycosaminoglycan of the interstitial matrix, helps to retain water in
      the lung interstitium and to exclude proteins. Marked reduction of interstitial
      hyaluronan by infusion of hyaluronidase decreased the resistance to fluid
      transport and decreased water retention in the interstitium, and thus accelerated
      lymphatic removal of fluid filtered across capillary walls. However, reduction of
      hyaluronan increased the accumulation of neutrophils in the lung and exacerbated
      acute lung injury caused by pancreatic elastase. Interstitial hyaluronan may
      protect against acute inflammatory changes in elastase-induced lung injury.

PMID- 8752512
TI  - [Acute lung injury and chemical mediators].
AB  - The essential abnormality in acute lung injury is an increase in pulmonary
      permeability. The mechanisms involved are complex, and may include direct effects
      on endothelial cells; the actions of neutrophils, macrophages, and lymphocytes;
      and chemical mediators generated by these cells. Neutrophils are known to be
      important in acute lung injury, and the mediators they produce, especially
      protease and oxidants, may be responsible for endothelial cell injury. We studied
      the roles of neutrophil elastase and oxygen radicals in acute lung injury by
      Escherichia coli endotoxin in sheep with lung lymph fistulae. The results of
      these and other studies indicate that these substances are related to the
      increase in pulmonary permeability during the late phase of injury.

PMID- 8752514
TI  - [Pathophysiology and Diagnosis of the acute respiratory distress syndrome].
AB  - We studied methods for diagnosing the acute respiratory distress syndrome (ARDS)
      based on its characteristic abnormalities. A gamma-ray external counting method
      with Tc-99m human serum albumin revealed that pulmonary microvascular
      permeability was abnormally high in patients with ARDS. With this method, ARDS
      could be distinguished from cardiogenic pulmonary edema. Levels of interleukin-8
      in bronchoalveolar fluid from patients with septic ARDS, reexpansion pulmonary
      edema, and inhalation burn injury were abnormally high. In 21 patients with acute
      lung injury, 15 of whom had ARDS, plasma concentrations of three inflammatory
      markers were measured: thiobarbituric acid reactive material which reflects cell
      membrane lipid peroxidation; 7S collagen, a component of basement membrane; and
      the soluble form of P-selectin, an adhesion molecule. Levels of all three were
      abnormally high in patients with ARDS, and correlated with the degree of lung
      injury and with the outcome in these patients. We conclude that these
      measurements in plasma or bronchoalveolar lavage fluid may enable us to assess
      the severity of ARDS.

PMID- 8752513
TI  - [Role of adhesion molecules in the development of acute lung injury].
AB  - Polymorphonuclear neutrophils (PMN) play a central role in the development of
      acute lung injury. Sequestered and activated PMN in the lungs produce
      inflammatory mediators such as reactive oxygen intermediates and proteases, which
      increase endothelial permeability. The interaction of PMN and endothelial cells
      mediated by adhesion molecules is a crucial step in PMN-mediated injury. These
      molecules mediate the adhesion of PMN to endothelial cells, and the migration of
      PMN into the interstitium. In these steps, PMN are also activated by adhesion
      molecules. We examined the role of adhesion molecules in the PMN-mediated
      increase in endothelial permeability in vivo with a rat model of lung injury, and
      in vivo with an assay of endothelial monolayer permeability.

PMID- 8752515
TI  - [Diagnosis of acute respiratory distress syndrome: analysis of bronchoalveolar
      lavage fluid].
AB  - To better understand the pathogenesis of acute respiratory distress syndrome
      (ARDS), we analyzed bronchoalveolar lavage fluid (BALF) from patients with ARDS
      (n = 89, survival rate = 56.2%), who were admitted to our intensive care units
      over the past 7 years. ARDS was diagnosed when the lung injury score proposed by
      Murray et al was greater than 2.5. The BALF had very high centrations of albumin,
      a marker of permeability edema, along with remarkably high neutrophil counts,
      percent neutrophils, neutrophil-elastase, and interleukin-8, markers of
      neutrophil-related lung injury. In addition, the level of IL-8 in BALF was higher
      in non-survivors than in survivors. Levels of thrombin-antithrombin complex
      fibrin degenerative product and soluble thrombomodulin (recently recognized as a
      natural anticoagulant combined with vascular endothelial cells) were very high in
      BALF from patients with ARDS. Moreover, the level of soluble thrombomodulin in
      BALF was higher in non-survivors than in survivors. There were significant
      relationships between these neutrophil-related markers and markers of abnormal
      coagulation. The results of the BALF analysis suggest that accumulation and
      activation of neutrophils can affect thrombomodulin on vascular endothelial
      cells, which can activate thrombin and cause the coagulopathy seen in ARDS.

PMID- 8752516
TI  - [Interstitial pneumonia associated with collagen vascular diseases: histological
      findings, and cells in bronchoalveolar lavage fluid].
AB  - Collagen vascular diseases are systemic inflammatory disorders, and autoimmune
      abnormalities play an important role in their pathogenesis. The lungs are often
      involved and the manifestations can be quite heterogenous. Cases of interstitial
      pneumonia associated with collagen vascular disease must be distinguished from
      infection, malignancy, cardiac failure, and renal failure. The diversity of
      interstitial pneumonia can be seen in the results of computerized tomography and
      in cells found in bronchoalveolar lavage fluid (BALF). We examined the
      heterogeneity of interstitial pneumonia diagnosed by open lung biopsy, and
      evaluated the diagnostic accuracy of BALF cell findings by comparing then with
      results of histological studies. Three patterns of BALF cell findings were
      defined, and were used to study the heterogeneity of the interstitial pneumonia
      associated with collagen vascular diseases: sarcoidosis, usual interstitial
      pneumonia (UIP), and bronchiolitis obliterans organizing pneumonia (BOOP). In 36
      patients with collagen vascular diseases, interstitial pneumonia was diagnosed by
      open lung biopsy: 15 patients had rheumatoid arthritis, 3 had systemic lupus
      erythematosus, 9 had systemic sclerosis, 6 had dermatomyositis/polymyositis, and
      4 had Sjogren's syndrome. As disease controls, 78 patients with idiopathic
      pulmonary fibrosis and 12 with idiopathic BOOP diagnosed by open lung biopsy were
      used. BAL was done before the biopsy. In most patients, the interstitial
      pneumonia associated with systemic sclerosis was UIP and the BALF cell pattern
      was a UIP-pattern. In addition, BALF UIP-patterns were associated with histologic
      findings of UIP in samples obtained by open lung biopsy. In contrast, other
      collagen vascular diseases tended to be associated with a BALF BOOP-pattern,
      which included various histological findings. Thus, the BALF BOOP-pattern, is
      associated with BOOP, with cellular interstitial pneumonia, with lymphocytic
      interstitial pneumonia, and with UIP. The BALF sarcoidosis-pattern is rare in
      patients with interstitial pneumonia associated with collagen vascular diseases.

PMID- 8752517
TI  - [Clinical and immunological study of airway disease in collagen vascular
      disease].
AB  - We studied the clinical and immunological characteristics of patients with
      bronchiolar diseases associated with collagen vascular disease (15 patients with
      rheumatoid arthritis and 1 primary Sjogren's syndrome). Histological examinations
      showed that 9 patients had follicular bronchiolitis and 7 had bronchiolitis
      obliterans. Follicular bronchiolitis was characterized by hyperplasia of bronchus
      associated lymphoid tissue, and immunohistochemical studies revealed that the
      pattern of distribution of T cells and B cells in bronchus-associated lymphoid
      tissue from patients with follicular bronchiolitis was similar to that in diffuse
      panbronchiolitis, which may be used as a representative model of chronic
      respiratory infection. In addition, bacterial cultures of sputum samples were
      positive in 44% of patients with follicular bronchiolitis and in 71% of patients
      with bronchiolitis obliterans. These results suggest that antigen stimulation is
      involved in the development of bronchiolar diseases associated with collagen
      vascular disease.

PMID- 8752518
TI  - [Interstitial lung disease in patients with connective tissue diseases].
AB  - Interstitial lung disease is a significant prognostic factor in connective tissue
      diseases. To further clarify clinical and immunological features of interstitial
      lung disease, we studied 894 consecutive patients with connective tissue diseases
      first evaluated between 1970 and 1993. Interstitial lung disease was found in 101
      of 181 (56%) patients with systemic sclerosis, 92 of 183 (50%) with overlap
      syndrome, 35 of 76 (46%) with polymyositis/dermatomyositis, and 13 of 444 (3%)
      with systemic lupus erythematosus (p < 0.05, systemic lupus erythematosus vs.
      other connective tissue diseases). The presence of interstitial lung disease
      correlated with decreased survival in systemic sclerosis and in
      polymyositis/dermatomyositis, but not in overlap syndrome or in systemic lupus
      erythematosus. Interstitial lung disease in patients with connective tissue
      diseases was classified into two types: acute (n = 8) and chronic (n = 233).
      Among the 8 patients with acute disease, 4 (all with dermatomyositis) died of
      respiratory failure and 3 (all with systemic lupus erythematosus) responded to
      corticosteroids. Among the 233 patients with chronic interstitial lung disease,
      20 had polymyositis/dermatomyositis with anti-aminoacyl tRNA synthetase
      antibodies and 40 had overlap syndrome with anti-U1 RNP antibodies. Respiratory
      failure in these patients was not frequent and occurred late in the course of the
      disease. As a cause of death, respiratory failure was associated with
      autoantibodies to topoisomerase I and aminoacyl tRNA synthetase but not anti-U1
      RNP. Autoantibodies to aminoacyl tRNA synthetases were detected before the
      development of interstitial lung disease in 9 patients with
      polymyositis/dermatomyositis. We conclude that the clinical features of
      interstitial lung disease associated with connective tissue diseases vary with
      the type of connective tissue disease, and that analysis of autoantibodies can be
      useful in establishing a diagnosis and in forecasting the course and outcome.

PMID- 8752519
TI  - [Pulmonary manifestation of collagen vascular diseases: role of cytokines in
      interstitial pneumonia associated with collagen vascular diseases].
AB  - Although the pathological patterns of interstitial pneumonia associated with
      collagen vascular disease (CVD-IP) resemble those of usual interstitial pneumonia
      in idiopathic interstitial pneumonia (IIP), the clinical features of CVD-IP and
      IIIP are quite different. We evaluated the differences between these conditions,
      with regard to the expression of genes in cells obtained by bronchoalveolar
      lavage. The reverse transcription-polymerase chain reaction was used to measure
      the levels of mRNA for IL-1 beta, TNF-alpha, IL-8, TGF-beta, PDGF-B, and IGF-1,
      and no significant differences were found between patients with CVD-IP and those
      with IIP. However, differential display analysis revealed a fragment that can be
      considered to have been derived from an unknown gene mRNA, and this was found
      only in patients with pulmonary fibrosis associated with progressive systemic
      sclerosis. Expression of specific genes may differentiate CVD-IP from IIP.

PMID- 8752520
TI  - [Expression of bc1-2 protein in collagen vascular diseases with pulmonary
      interstitial involvement].
AB  - Expression of bc1-2 protein was studied immunohistochemically in 25 patients with
      collagen vascular diseases and in 10 patients with idiopathic interstitial
      pneumonia. The collagen vascular diseases included rheumatoid arthritis (n = 9),
      progressive systemic sclerosis (n = 9), polymyositis/dermatomyositis (n = 4),
      Sjogren's syndrome (n = 2), and systemic lupus erythematosus (n = 1). All 35
      patients underwent open lung biopsy; cellular infiltration, fibrosis, and
      lymphoid aggregation were scored according to Cherniack's classification. T
      lymphocytes (CD43: DFT-1) and B lymphocytes (CD20:L-26) were also evaluated.
      Expression of bc1-2 protein was dominant in T lymphocytes infiltrating the
      alveolar interstitium and in B lymphocytes in the mantle zone of lymphoid
      follicles. In collagen vascular diseases, the degree of expression of bc1-2
      protein in those T lymphocytes was closely related to the alveolar lymphocyte
      infiltration score. However, these findings were not marked in the patients with
      idiopathic interstitial pneumonia, and were not related to the underlying disease
      in the patients with collagen vascular diseases. The expression of bc1-2 protein
      in T lymphocytes was not related to fibrosis or to lymphoid aggregation.
      Expression of bc1-2 protein in B lymphocytes did not correlate with pathological
      scores or with underlying disease. Bc1-2 protein has been recognized as an
      oncogene that suppresses apoptosis. Marked expression of bc1-2 protein in T
      lymphocytes from patients with collagen vascular diseases indicates that
      oversuppression of apoptosis may be related to the pathogenesis of pulmonary
      interstitial involvement in these conditions. Further clinicopathological studies
      focusing on apoptosis in collagen vascular diseases and in idiopathic
      interstitial pneumonia are needed.

PMID- 8752522
TI  - [What is brain's senility?].
AB  - Japan is the nation of the highest longevity in the world, average length of life
      being 76.57 years old for man and 82.98 for woman in 1994, according to the
      Ministry of Health and Welfare of Japan. How to cope with normal or abnormal
      senility is the matter of utmost interest at present time. Therefore, this
      symposium was very important, and was open not only for physicians, but for
      citizens. The five expert lecturers made the excellent presentations on these
      difficult topics from basic to clinical standpoints. The participants were all
      impressed by these up-to-date talks and discussions throughout the sessions.

PMID- 8752521
TI  - [Pulmonary involvement of collagen vascular diseases: studies on prognostic
      factors from basic and clinical viewpoints].
AB  - In 715 patients with collagen vascular diseases, interstitial lung disease and
      pulmonary hypertension were found to be important causes of death (37.5% and 6%,
      respectively). The prognosis of interstitial lung disease associated with
      collagen vascular disease was better than that of idiopathic interstitial
      pneumonia; patients with the latter were more likely to experience exacerbations.
      A distinct subgroup of patients with dermatomyositis and interstitial lung
      disease with a rapidly progressive course was characterized by mild muscle
      symptoms, low levels of creatine phosphokinase and negative tests for anti-Jo-1
      antibody. CT scores and analysis of bronchoalveolar lavage fluid proved to be of
      some value in predicting outcome. Measurement of IL-6 in bronchoalveolar lavage
      fluid and local immunostaining for this pro-inflammatory cytokine were helpful in
      evaluating responses to therapy.

PMID- 8752523
TI  - [Aging brains and the dementias].
AB  - Dementia has been defined generally as an acquired persistent impairment of
      intellectual function caused by organic brain diseases. The rapidly increasing
      incidence of dementias has been claimed on the basis of epidemic studies in Japan
      as well as in Western developed countries. These observations are justified by
      the facts that most dementias are found in people over the age of 65 years, and
      that the elderly population is increasing rapidly resulting in both absolute
      numbers and percentage of the population. In Japan, it is estimated that 1.5
      million of demented persons are present. The purpose of this paper is to describe
      clinical manifestations and morphological alterations of aged and demented
      individuals, diagnostic process to differential diagnosis to provide
      knowledgeable approach to management, and adequate care of the demented
      individuals. In aged brain, there are a variety of morphological changes. Some of
      these are usually observed in aged brains; atrophy of the brains, loss of
      neurons, accumulations of lipofuscin. Others observed in pathologically aged
      brains, or accelerated aging brains are Alzheimer's neurofibrillary tangles,
      senile plaques, and granulovacuolar degeneration. Psychiatric manifestations
      associated with aging and dementing diseases are described. It should be realized
      that clinical manifestations of the demented reflect primarily the topography of
      the organic lesions in the brain, and functional alterations, and are influenced
      by psychological and socio-environmental factors.

PMID- 8752524
TI  - [Image analysis in patients with dementia].
AB  - There are a number of noninvasive imaging methods in patients with dementia,
      including X-ray CT, MRI, SPECT and PET. Anatomical imaging using CT and MRI is
      often used for assessing severity of brain atrophy, which is commonly seen in
      patients with dementia. However, the early detection of brain abnormalities seem
      to be limited with these methods. Brain functional studies using radionuclide
      techniques have been recently developed with introduction of a variety of new
      radiopharmaceuticals. Among them, brain perfusion SPECT which is clinically
      available in most of the hospitals, is considered as a powerful means for
      accurate diagnosis and assessment of severity of dementia. Hypoperfusion is
      commonly seen in bilateral parieto-temporal cortex (association cortex) in
      patients with Alzheimer's disease. Frontal hypoperfusion is seen in the advanced
      cases of Alzheimer's disease. This disease is easily differentiated with multi
      infarct dementia where multiple asymmetrical hypoperfusion is seen in the brain
      cortex on SPECT. More importantly, such functional abnormality is often observed
      in patients with normal findings in CT or MRI, indicating clinical value of brain
      perfusion SPECT for early detection of Alzheimer's disease. Bilateral
      hypoperfusion is noted in the frontal cortex in patients with Pick disease.
      Recently biochemical imaging can be obtained with positron emission tomography
      (PET) using various physiological tracers labeled with C-11, N-13, O-15, and F
      18. Cerebral perfusion, metabolism and receptor functions can be quantitatively
      measured in vivo. The PET study nicely demonstrated that hypometabolism in
      bilateral parieto-temporal cortex in patients with Alzheimer's disease.
      Furthermore, glucose metabolism is considered to be further suppressed compared
      to perfusion, indicating suppression of brain synaptic function in this disease.
      In conclusion, brain functional imaging using SPECT and PET is useful for the
      detection and evaluation of a variety of dementia.

PMID- 8752525
TI  - [Neurochemical aspect of brain aging--neuronal death and decreased synaptic
      functions].
AB  - Several diseases related to brain aging seem to be due to neuronal loss and
      decreased synaptic functions. Therefore it is important to clarify the cellular
      and molecular mechanism of age-related-neuronal death and -reduction in synaptic
      activities in the brain. I here review recent advances in cellular and molecular
      studies on neuronal death and the decrease in synaptic functions. Neuronal death
      is caused not only with physiological aging but also by several pathological
      states such as 1) results from abnormal metabolism of beta APP (Alzheimer's
      disease), 2) increased level of extraneuronal glutamate and intracellular Ca2+/NO
      (cerebral ischemia), and 3) appearance of neurotoxic MPP+ (1-methyl-4-phenyl
      pyridinium ion) (Parkinson's disease) etc. From neurotoxicological aspect of
      neuro-glial interaction, I introduce recent findings on signaling pathways of NO
      synthase induction in glial cells and cytotoxic action of NO in neurons.
      Furthermore I also describe and discuss our findings obtained in the brain of old
      rats as well as in senescence accelerated mice (accelerated aging substrain of
      AKR/J-mouse) regarding age-related changes in synaptic activity and
      neurotransmittor receptor-mediated signaling system.

PMID- 8752526
TI  - [Clinical aspects of dementia].
AB  - Differential diagnosis of dementing diseases is very important to rule in the so
      called treatable dementia. The new DSM-IV criteria for dementia include memory
      disturbances and one or more of aphasia, apraxia, or frontal lobe dysfunctions as
      essentials. Alzheimer disease requires, in addition, slowly progressive course
      and ruling out other brain or systemic diseases. Vascular dementia requires focal
      neurological or neuroimaging signs. Other diseases which cause dementia include
      chronic subdural hematoma, infection and brain tumor. CT or MRI can readily
      diagnose them if suspected and they may be treated. Systemic diseases associated
      with treatable dementia include electrolyte disturbances, hypothyroidism, vitamin
      deficiency, alcohol or drug intoxication, syphilis and HIV infection. Prevention
      of dementia seems to be the future problem as we could prevent cerebrovascular
      diseases by treating hypertension.

PMID- 8752527
TI  - [Aging of brain and the maintenance of the function].
AB  - Some diseases develop dementia, but they may be dementia-like-situation, such as
      depression and drugs induced one. There are many causes as an etiology of
      dementia. Among them a lots of diseases are treatable dementia, like chronic
      subdural hematoma, normal pressure hydrocephalus, brain abscess, syphilis,
      herpetic encephalitis, Wilson's disease, hypothyroidism, parathyroid disease,
      vitamin B12 deficiency, pellagra etc. In examination of patients with dementia,
      exact history taking, physical examination and laboratory examination should be
      done carefully. In the patients with Alzheimer's dementia and cerebrovascular
      disease's dementia, as many risk factors are known, we must try to treat and
      exclude each risk factor and protect the dementia. Inactivity of physical and
      mental function is reported to induce the dementia, so activation of them could
      prevent the development and the progression of dementia. In future the methods of
      the prevention of apoptosis and cell death would be found in order to prevent the
      dementia. Free radical scavenger, nerve trophic factor, cytokine, antagonist of
      glutamate etc. will have the possibility to become the medicine for the dementia.
      The nerve transplantation, nerve transmitter, nerve peptide etc. might serve as
      the allopathic treatment for the dementia.

PMID- 8752528
TI  - [Development of collagen vascular diseases and production of autoantibodies in
      HTLV-I env-pX transgenic rats].
AB  - Human T lymphocyte virus type I (HTLV- I) is now known to be associated with a
      number of diverse clinical disorders, not only adult T cell leukemia but also
      HTLV- I associated myelopathy/tropical spastic paraparesis, HTLV- I -associated
      arthropathy, HTLV- I uveitis, and probably Sjogren's syndrome, T cell alveolitis,
      polymyositis, and infective dermatitis. To investigate virus-host interactions
      and pathogenetic mechanisms in these diverse disorders, inbred rat, which is
      susceptible to HTLV- I infection and develops HAM/TSP-like disease by HTLV- I
      infection, was used as a host of HTLV- I gene transfer model. HTLV- I LTR-env-pX
      LTR construct was injected to rat ova, and two lines of the transgenic rat (env
      pX rat) were established. Both lines of env-pX rats expressed HTLV- I env and pX
      genes in various tissues, and developed a wide spectrum of collagen vascular
      diseases, including chronic destructive arthritis similar to rheumatoid
      arthritis, necrotizing arteritis mimicking polyarteritis nodosa, myositis,
      myocarditis, and chronic sialoadenitis and dacryoadenitis resembling Sjogren's
      syndrome in humans. Thrombosis and thymic atrophy were also observed. These rats
      showed hyper-gamma globulinemia and a number of autoantibodies, including high
      titered rheumatoid factors, anti-dsDNA antibodies and anti-cardiolipin antibodies
      were presented in the serum. Results suggest that the HTLV- I env-pX gene may
      play a pathogenic role in development of collagen vascular diseases associated
      with autoimmune phenomenon. The env-pX rat appears to be a suitable animal model
      for elucidating pathogenetic mechanisms implicated in HTLV- I -induced diseases
      and also in various collagen vascular diseases of unknown etiology in humans.

PMID- 8752529
TI  - [Function of human immunodeficiency virus type 1 nef gene product in virus
      replication].
AB  - We comparatively analyzed the replication kinetics of wild-type (wt) and nef
      mutant human immunodeficiency virus type 1 (HIV-1) in several CD4-positive cell
      lines, in order to clarify the molecular function of Nef protein. The delayed
      growth of nef mutant virus was observed at the initial stage of replication in
      all cell lines examined. This phenomenon was greatly amplified in the absence of
      vpu gene. In order to determine the infection stage in viral replication cycle
      which is specifically affected on virus replication rate in the presence of the
      Nef protein, we first examined the difference between wt and nef mutant viruses
      in the virus production rate from transfected cells, and found that the both
      viruses were produced with equal efficiency. This result showed that Nef protein
      could be dispensable for virion production. Therefore, early infection stages
      were focused by single-round infection assay, and the nef mutant virus was found
      to be much less infectious than wt virus. This indicated that the effect of Nef
      protein was exhibited in the early phase of a virus replication cycle, during
      viral adsorption to integration. By entry assay using wt and nef mutant virions,
      it was revealed that the Nef protein was required for efficient viral entry.
      These data suggest that the Nef protein might play a role in efficient
      incorporation of the Env protein into the virions, leading to enhanced viral
      infectivity.

PMID- 8752530
TI  - [A novel nonsense point mutation in the arylsulfatase B gene with a severe type
      Maroteaux-Lamy syndrome].
AB  - Maroteaux-Lamy syndrome (MLS, also known as Mucopolysaccharidosis VI) is an
      inherited lysosomal disease due to a deficiency of the enzyme arylsulfatase B
      (ASB). Clinically, severe, intermediate and mild types are classified according
      to the symptoms and the age of onset. In recent years, several cases have been
      reported in which various mutations have been found by sequence analysis of ASB
      cDNA or genomic DNA. All of these mutations were reported occurred in single
      patients. Here I report a severe type MLS patient. A new point mutation was found
      on ASB gene which resulted in a stop codon at ASB peptide 421 (Glu). Due to this
      point mutation, a peptide fragment composed of 112 amino acids should have been
      deleted out. This point mutation was confirmed as a homoallele by direct sequence
      analysis of genomic DNA. Expression experiment on this point mutation revealed
      that the mutant produced neither mature ASB protein nor enzyme activity.

PMID- 8752531
TI  - [The mechanism of distant metastases of alveolar hydatid disease].
AB  - The mechanism of the distant metastasis of echinococcosis was investigated using
      jirds (Meriones unguiculatus) by inoculation of fractions obtained from
      echinococcal lesions formed in the peritoneal cavity of cotton rats (Sigmoid
      hispidus). Protoscoleces, cysts, and germinal cells were fractionated from the
      peritoneal lesions of the cotton rats injected peritoneally with echinococcal
      germinal cells. Each fraction (protoscoleces; 500 pieces, cysts; 50 pieces,
      germinal cells; 2 x 10(7) cells) suspended in 0.2 ml of PBS was injected into
      either the left inguinal vein (IV group) or the mesenteric vein (MV group) of
      seven week-old jirds. Eight weeks after the injection, the jirds were sacrificed
      and examined macroscopically and microscopically. In IV group, one of 10 jirds
      had echinococcal lesions in lung, bilateral adrenal, brain, para-aortic lymph
      node and left inguinal lymph node by inoculation of only germinal cells. Another
      one had lung lesions formed by cysts inoculated. In MV group, both intrahepatic
      and pulmonary echinococcal lesions by inoculation of germinal cells were observed
      in 3 out of 5 jirds. Cysts inoculated formed intrahepatic lesions in all 5 jirds.
      However, protoscoleces inoculated through both routes never formed echinococcal
      lesions in any organs. The typical lesions of echinococcosis were observed in all
      lesions without protoscoleces and calcification. These results indicate that
      germinal cells in intrahepatic echinococcal lesions might invade into the
      intrahepatic vein and metastasize to other organs.

PMID- 8752532
TI  - Changes in brain neurotransmitters in hypothalamus related to feeding behavior in
      LEC rat.
AB  - In the present study, neurotransmitters related to the regulation of food intake
      were investigated in hypothalamus of LEC rats. The experiment was conducted using
      LEC and LEA (control) rats aged 4, 10 and 20 weeks. Cu concentration in
      hypothalamus of LEC rats aged 4 weeks was lower than that in the control, and
      similar to the control in 10 weeks of age. In contrast, Cu concentration of LEC
      rats aged 20 weeks was significantly higher (p < 0.01) than that in the control.
      The acetylcholine release from lateral hypothalamus of LEC rats aged 4 weeks was
      significantly higher (p < 0.05) than that in the control, but no significant
      difference of acetylcholine release was found between LEC and control rats aged
      10 and 20 weeks. The metabolism of serotonin (5-HT) in hypothalamus of LEC rats
      was facilitated in 20 weeks of age. Furthermore, the 5-hydroxytryptophan,
      precursor of 5-HT in LEC rats aged 10 weeks was significantly higher (p < 0.05)
      than that in the control. No significant difference was found in norepinephrine
      (NE), dopamine (DA), 3, 4-dihydroxyphenyl acetic acid and homovanilic acid
      concentrations in each age of hypothalamus, except a significant decrease in NE
      concentration in LEC rats aged 10 weeks (p < 0.05). The daily and total food
      intake were suppressed in LEC rats from a young age. Furthermore, blood glucose,
      albumin and total cholesterol concentrations in LEC rats were lower than those in
      the control rats. The present study demonstrated that age dependent changes in Cu
      concentration and the metabolism of neurotransmitters related to the regulation
      of food intake occurred in hypothalamus of LEC rats. These results suggest that
      suppression of the food intake observed in LEC rats is not only due to hepatitis
      but also due to suppressive effects of feeding regulation center in central
      nervous system.

PMID- 8752533
TI  - [The long-term effect of day care rehabilitation on individuals with dementia].
AB  - In the treatment of senile dementia, rehabilitation rather than drugs, could
      result in more positive long-term effects. A Day Care program designed for
      individuals with Senile Dementia of the Alzheimer type (SDAT) and Vascular
      Dementia (VD:MID and BD), activates the brain through memory training, creative
      arts therapy, physical activity, and social interaction. The objective of this
      study is to determine if Day Care can modify the patients intellectual decline or
      even alter the natural course of the dementing illness. 135 SDAT and 213 VD
      patients were studied over three years. ADL (Activities of Daily Living)
      measurements were evaluated by the Barthel Index and cognitive measurements by
      the NM-scale. The Wilcoxon test and the Sign test were carried out using the BI
      and NM-scale scores. These results indicated a decline or arrest in the
      progression of SDAT and VD as determined by the multiple logistical models. The 8
      variables (risk factors, medication, age at onset, self-rehabilitation, family
      support, sex, grade of dementia and Day Care) influence on the survival curves
      was calculated using the Kaplan-Meire Life table method. The Cox proportional
      hazard analysis was then used to examine the relationship between the 8 variables
      and dementia. The significantly positive results from these four analyses of the
      ADL and cognitive measurements indicate that Day Care programs clearly retards
      the progression of intellectual decline in dementia patients and improves the
      quality of life (QOL) in all cases. In VD patients the mortality rate was notably
      decreased through Day Care. These results make one consider the benefits of
      introducing such programs into society as a strong treatment against the onset of
      dementia developing into severe, dehabilitating dementia. However a healthy diet,
      a physically and mentally active life, as well as early diagnosis, are the best
      preventions against dementia.

PMID- 8752534
TI  - [Non-photic entrainment of human circadian clock--effects of forced sleep-wake
      schedule on the circadian rhythm in plasma melatonin].
AB  - The present study was performed in order to have better understanding of the
      human circadian system. Two hypotheses concerning with the human circadian system
      have been advanced. One is a two self-sustained oscillator hypothesis, and the
      other is a two process hypothesis. Both hypotheses are based on a phenomenon
      called internal desynchronization. A major difference between the two hypothesis
      is that sleep or wakefulness does not affect the circadian oscillation in the two
      process hypothesis, while a mutual interaction between sleep (wakefulness) and
      the circadian oscillation is not excluded in the two oscillator hypothesis. On
      the other hand, social sues such as a sleep-wake schedule and regular contact
      with others have been considered as a major time cues (zeitgeber) for the human
      circadian rhythm. However, lights brighter than 5,000 lux was recently
      demonstrated to be capable of resetting the human circadian rhythm, and it is now
      a matter of debate whether the resetting effect of social cues is due to the
      light-dark cycle inevitably associated with a sleep-wake schedule. In the present
      study, the effects of forced sleep-wake schedules on the circadian rhythm in
      plasma melatonin and rectal temperature were examined in subjects under temporal
      isolation, which are not explained by the two process hypothesis. As a result,
      the forced sleep-wake schedule of 24.0-hour period in dim light condition (below
      200 lux) entrained the circadian rhythms in 3 out of 8 subjects. The forced
      schedule in extremely dim light condition (below 5 lux) was also capable of
      entraining the circadian rhythm. On the other hand, the forced schedule of 23.5
      hour period showed no entrainability. It is concluded that the non-photic
      entrainment is operating in the human circadian clock, which supports the two
      self-sustained oscillator hypothesis.

PMID- 8752535
TI  - [Histopathological prognostic factors in 146 patients with renal cell carcinoma:
      comparison between incidental and non-incidental cases].
AB  - To characterize the prognostic factors among pathological structural pattern,
      cell type, infiltration, and incidental or non-incidental renal cell carcinoma
      (RCC), we reviewed the records of 146 patients with RCC who underwent nephrectomy
      at our institute. The patients were 26 to 86 years old (mean age 58). The men-to
      women ratio was 3.2:1. The tumor originated in the right kidney in 83 patients
      and in the left in 63. The solid pattern was associated with poorer survival than
      other patterns (p < 0.01). Spindle or pleomorphic cell type had poorer survival
      than common type (p < 0.01). The number of incidentally discovered RCC has
      increased since 1986, and survival is better than in non-incidental RCC, because
      of smaller tumor size, low stage tumor (stages 1, 2; 83.6%), and fewer papillary
      or solid type. In addition, there were no spindle or pleomorphic cell type, grade
      3 or INF gamma-positive case. Survival is good even when the tumor is large.

PMID- 8752536
TI  - [Immunohistochemical examination for p53 overexpression in Ta bladder cancer with
      disease progression].
AB  - To evaluate the significance of p53 overexpression on the progression of bladder
      cancer, seven patients with Ta bladder cancer who eventually progressed to the
      invasive stage ( > or = stage T1) were immunohistochemically analyzed. The
      immunohistochemical study was performed using the p53 protein antibody on
      formalin-fixed, paraffin-embedded tissue sections from all primary and recurrent
      tumors. In three patients, immunoreactivity was detected only at the time of
      disease progression, suggesting that p53 mutation may be related to the disease.
      However, since no staining could not be found in stage Ta bladder cancer, the
      patient with a risk of progression could not be detected by this
      immunohistochemical study.

PMID- 8752537
TI  - [Combined hormone-chemotherapy for stage D2 prostatic cancer: starting time of
      chemotherapy in relation to hormone therapy].
AB  - We retrospectively analyzed 29 patients with stage D2 prostatic cancer who had
      been treated with chemotherapy at the urological clinic of Tokyo Medical and
      Dental University Hospital between 1983 and 1992 to evaluate the efficacy of
      chemotherapy for advanced prostatic cancer. The patients were divided into three
      groups according to the starting time of chemotherapy in relation to hormone
      therapy; 9 patients who received chemotherapy more than four weeks after the
      initial hormone therapy (group H), 9 patients who received chemotherapy only or
      in combination with the hormone therapy more than four weeks previously (group
      C), and 11 patients in whom both therapies were started within four weeks (group
      HC). Follow-up period ranged from four to 108 months averaging 35. Combination
      chemotherapy including cisplatin was administered one to 17 times with the median
      of five. The five-year survival rates estimated by Kaplan-Meier method were 18%
      in group H, 28% in group C, and 78% in group HC, respectively (HC vs. C: p <
      0.05, HC vs. H: p = 0.059). These findings indicate that a combination
      chemotherapy including cisplatin may improve the prognosis of patients with
      advanced prostatic cancer when it is started with the initial hormone therapy
      simultaneously.

PMID- 8752538
TI  - Effect of alpha-blockers on epididymal sperm concentration, motility and
      testicular productivity in the rat.
AB  - The present study was undertaken to determine whether alpha-blockers affect
      epididymal sperm parameters and testicular spermatogenesis. Sprague-Dawley rats
      were given orally a 1 mg/kg body weight dose of Bunazosin, a selective alpha
      adrenoreceptor antagonist, daily for one month as a short-term administration
      group and three months as a long-term administration group. Using a micropuncture
      technique, epididymal sperm concentration and sperm motility were measured.
      Epididymal sperm concentrations were significantly increased in the Bunazosin
      group, but progressive motility of spermatozoa were not altered. Daily testicular
      sperm production was also increased after administration of Bunazosin. There were
      no differences in epididymal sperm concentration and daily sperm production
      between the one-month group and three-month group. An epididymal wide storage
      capacity and short transit time after administration of the alpha-blocker could
      increase the sperm concentration in the cauda epididymidis. Because there were no
      differences in the epididymal sperm parameters and daily testicular sperm
      production between the two groups, these changes may occur at 1 month after
      administration of the alpha-blocker. Moreover, the alpha-blocker might affect
      testicular function.

PMID- 8752539
TI  - [Bilateral renal cell carcinoma with extension into the vena cava associated with
      von Hippel-Lindau disease: a case report and review of the literature].
AB  - We report a case of bilateral renal cell carcinoma with extension into the
      inferior vena cava associated with von Hippel-Lindau (VHL) disease. A 52-year-old
      woman was referred to our hospital for further examination of bilateral renal
      masses which were found on abdominal ultrasound examination. The diagnosis was
      confirmed with renal angiography, abdominal computed tomography (CT), abdominal
      magnetic resonance-CT (MRI), cavography and head MRI. Right adjunctive
      nephrectomy and removal of the tumor thrombus were performed. She has been
      treated with interferon-alpha after the operation. The analysis of her DNA by
      using single strand conformational polymorphism revealed a VHL gene abnormality.

PMID- 8752540
TI  - [A case of renal cell carcinoma with an extremely high serum carcinoembryonic
      antigen level].
AB  - A case of renal cell carcinoma with extremely high serum carcinoembryonic antigen
      (CEA) levels is presented. A 57-year-old female complained of left flank pain.
      Computerized tomographic (CT) scan revealed left renal tumor and laboratory
      examination revealed an extremely high serum level of CEA (815 ng/ml). No
      abnormal findings were recognized in gastrointestinal or genital systems. Radical
      nephrectomy was done. The histology was renal cell carcinoma (RCC, intermediate
      type, mixed type, pleomorphic cell type, G3 > G2, INF gamma, pT2, pV0). Tumor
      cells were positive for CEA by ABC-peroxidase staining. Levels of tumor markers
      decreased after operation. However, CEA levels rose again and lymph node
      metastases appeared. She died 6 months after operation.

PMID- 8752541
TI  - Renal oncocytoma treated by surgical enucleation: a case report.
AB  - We experienced a case of renal oncocytoma, in a 46-year-old woman. At a health
      examination, ultrasonography revealed a right renal tumor, and she was admitted
      to our hospital for evaluation. From the ultrasonogram, computerized tomography
      (CT) and angiography, we suspected a renal oncocytoma, but renal cell carcinoma
      was not completely ruled out. Since the location of the tumor seemed suitable for
      a local resection, we scheduled a surgical enucleation, but we intended to switch
      to a radical nephrectomy if examination of a frozen-section suggested renal
      cancer. Because the frozen findings were suggestive of an oncocytoma without
      malignancy, the surgical enucleation procedure was completed as scheduled.
      Pathological findings of the resected specimens were characterized by granular
      eosinophilic cytoplasm, and rounded nuclei without nuclear pleomorphism or
      mitotic figures. Electron microscopic studies revealed an increased number of
      mitochondria. The patient was accordingly diagnosed as having renal oncocytoma.
      We also reviewed the literature to elaborate procedures for a preoperative
      diagnosis and therapy for renal oncocytoma.

PMID- 8752542
TI  - [Unilateral multicystic dysplastic kidney in an adult: report of a case].
AB  - A case of unilateral multicystic dysplastic kidney in a 52-year-old woman is
      reported. Two abnormal round-like calcifications in left upper quadrant abdomen
      were found on upper gastrointestinal roentgengraphy for health screening. The
      computerized tomographic (CT) scan revealed a very small left kidney which was
      not enhanced and the ring and diffuse calcifications in it. It was not visualized
      by drip infusion pyelography. Left nephrectomy was performed. The kidney, which
      was very small, had two cysts the walls of which were calcified. The left ureter
      and renal vessels were absent. Histological appearance shows typical multicystic
      dysplastic kidney (MCDK). Literature is reviewed. However, the therapy for MCDK
      is still controversial.

PMID- 8752543
TI  - [Extirpation of total urinary tract as a final treatment for asynchronous
      multicentric urothelial cancer: a case report].
AB  - A 48-year-old male patient underwent transurethral resection (TUR) for solitary
      bladder tumor in January 1985. Pathological finding of the specimen was non
      invasive transitional cell carcinoma (TCC) G2 > G1. Following the operation,
      prophylactic intravesical instillation of antitumor agents, intrapelvic
      irradiation, and hyperthermia were done for the recurrences. In June 1987, left
      renal pelvic tumor revealed, and nephroureterectomy was performed. Histological
      examination of renal pelvic tumor showed TCC G1. Five months later, multiple
      bladder tumors and right renal pelvic tumor were detected. A total cystectomy,
      partial nephrectomy and nephrostomy were performed in February and March 1988.
      Pathology of the bladder and right kidney were TCC G3. One month after these
      operations, tumors recurred in the rest of the right kidney. Complete remission
      was achieved after systemic chemotherapy with methotrexate, vinblastine,
      doxorubicin and cisplatin (M-VAC). In January 1992, right renal pelvic tumor
      recurred again. After two cycles of M-VAC therapy, the rest of the right kidney
      was extirpated. Postoperative hemodialysis has been uneventful. He has lived
      without tumor recurrence for three years after the introduction of hemodialysis.

PMID- 8752544
TI  - [Emphysematous cystitis: a case report].
AB  - Emphysematous cystitis is a rare condition in which gas-forming organisms produce
      gas in the bladder wall and lumen. We present a case of emphysematous cystitis
      with neurogenic bladder. The patient was a 78-year-old man who complained of
      dysuria and lower abdominal soft mass. Urine culture yielded Klebsiella
      pneumoniae and Enterococcus faecalis. A plain X-ray film of upright position
      showed a large air-fluid level. The gas was demonstrated in the bladder wall and
      lumen on CT scan. These findings were compatible with that of emphysematous
      cystitis. The symptoms were improved and the intraluminal gas had disappeared on
      radiography after treatment with antibiotics. We reviewed 20 cases of
      emphysematous cystitis reported in the Japanese literature and reported clinical
      characteristics of 21 patients including ours here.

PMID- 8752545
TI  - [Primary transitional cell carcinoma of the prostatic urethra: a case report].
AB  - A case of primary transitional cell carcinoma of the prostatic urethra is
      reported. A 60 year-old male, with a chief complaint of difficult urination
      consulted our clinic on March, 1994. Urethrography and endoscopic examination
      revealed the solitary tumor of the prostatic urethra and transurethral resection
      was performed. Histologically, the tumor was Grade 2 transitional cell carcinoma
      without submucosal invasion. The post-operative course was uneventful and no
      recurrence has been seen. To our knowledge, including our case, 10 cases of
      primary transitional cell carcinoma of the prostatic urethra have been reported
      in the Japanese literature.

PMID- 8752546
TI  - [Polyorchidism: a case report and review of the literature].
AB  - An 11-year-old boy visited our department complaining of left scrotal painless
      mass from 6 months ago. The small mass was palpable beside the left testis.
      Ultrasonography shows isoechoic round shaped mass 5 mm in diameter. At surgery,
      the mass was connected with the left testis and epididymal head and sharply
      excised from them. Histological examination showed normal testicular
      architecture, but spermatogenesis was not found. We report the 18th case of
      polyorchidism in Japan and made some discussion about polyorchidism.

PMID- 8752547
TI  - [A case of labial adhesions with urinary retention].
AB  - A 69-year-old woman was admitted to our hospital complaining of urinary
      retention. On examination, the labia was found to be fused extensively, with a
      pinhole opening at the midline. The adhesions were separated under spinal
      anesthesia. One year after operation, there remains no recurrence. Etiological
      factor in labial adhesions are thought to include a combination of local
      inflammation and estrogen deficiency. In our case, the patient had hip joint
      disease. Hip joint disease is shown to influence the formation of adhesions by
      interfering with perineal hygiene and decreasing sexual activity.

PMID- 8752548
TI  - Healthy People 2000 Goal 1.12: primary care physicians and exercise counseling.
AB  - The Healthy People 2000 Goal 1.12 was designed to increase to 50% the number of
      primary care physicians who regularly counsel their patients concerning the
      appropriate frequency, duration, type and intensity of exercise. To assess the
      overall progress in relation to this goal, a survey of 212 physicians was
      conducted in an eight county region of northern Mississippi. Fifty-nine
      physicians completed and returned the survey. The findings indicate that 90% of
      the physicians perceive exercise to be important and that they are discussing
      exercise with approximately 50% of their patients aged 40 and older. However, the
      average length of the counseling segment is two minutes or less. It is therefore
      probable that the appropriate frequency, duration, type and intensity of exercise
      may not be adequately discussed during physician-based exercise counseling.

PMID- 8752549
TI  - Case records of the Department of Medicine University of Mississippi Medical
      Center. Acute panniculitis secondary to fungal infection, most likely Aspergillus
      species.

PMID- 8752550
TI  - A 5-year prospective multicenter follow-up report on overdentures supported by
      osseointegrated implants.
AB  - This report presents the results of a 5-year prospective multicenter study
      including nine centers worldwide. A total of 30 patients received 117 Branemark
      implants in the maxillae, and 103 patients received 393 implants in the
      mandibles. According to the protocol, all integrated maxillary implants were to
      be loaded; however, only two of four mandibular implants were planned for support
      of the overdentures, leaving the remaining implants covered by mucosa as backup
      for possible implant failures. Thirty-five patients (26.3%) who were provided
      with 127 implants (24.9%) were withdrawn from the study. Six patients treated in
      the maxilla lost all their implants and resumed wearing complete dentures. The
      cumulative success rates for implants and for overdentures supported by two
      implants in the edentulous mandible were 94.5% and 100%, respectively. The
      corresponding cumulative success rates for implants and for overdentures
      supported by an optimal number of implants in the maxilla were 72.4% and 77.9%,
      respectively. Significantly better jawbone characteristics at the time of implant
      surgery were considered to contribute to the better cumulative success rates in
      the mandibles. Mean marginal bone loss was 0.8 mm (SD 0.8) and 0.5 mm (SD 0.8)
      for loaded implants during a 5-year period of time in the maxillae and mandibles,
      respectively. Measurements of the clinical height of the abutment cylinders
      indicated a mean recession (0.2 mm) of peri-implant mucosa during the follow-up
      period in the mandibles. Conversely, hyperplasia was observed in the maxillae.

PMID- 8752552
TI  - Clinical effectiveness of implant-supported single-tooth replacement: the Toronto
      Study.
AB  - Forty-one patients received 49 single-tooth implants placed in different jaw
      locations. One implant was not osseointegrated at stage 2 surgery. Three
      successfully osseointegrated implants were not available for follow-up. Forty
      five implants were monitored for 1 to 8 years after loading. Each one of the
      implants met all of the traditionally accepted success criteria, except for nine
      individual implants that did not meet the proposed bone level criterion. No
      success criteria exist for natural teeth adjacent to implants. Although
      preliminary results are favorable, extensive long-term studies are needed to
      determine which specific criteria comprise optimal functional and esthetic
      results with minimal risk of morbidity.

PMID- 8752551
TI  - Immediate implantation of pure titanium implants into extraction sockets of
      Macaca fascicularis. Part I: Clinical and radiographic assessment.
AB  - Immediate implants have the advantages of few surgical exposures, short treatment
      time, and maintenance of alveolar bone height and width. The purpose of this
      study was to compare immediate implants with conventional implants (implants
      placed into ossified extraction sites) in adult monkeys. Forty-eight implants
      were placed and allowed to heal for a 6-month period. Following a 7-month loading
      period, the monkeys were sacrificed, and implant sections were evaluated
      histologically. Clinical and radiographic measurements showed few significant
      differences between immediate and control implants.

PMID- 8752553
TI  - Crevicular fluid enzymes from endosseous dental implants and natural teeth.
AB  - Several neutrophil-derived enzymes that are present in the gingival crevicular
      fluid have been evaluated for use as risk markers for periodontal disease
      progression. However, very little information is available about the presence of
      these enzymes in peri-implant tissues. The purpose of this cross-sectional study
      was to compare levels of enzymes in gingival crevicular fluid between natural
      teeth and endosseous dental implants and between well-integrated and failing
      implants. Scores of plaque and gingivitis were recorded for 68 integrated
      implants, five failing implants, and 34 natural teeth in 12 completely edentulous
      and 18 partially edentulous subjects. Samples of gingival crevicular fluid were
      obtained from these sites using filter paper strips and were assayed for levels
      of neutral protease, neutrophil elastase, myeloperoxidase, and beta
      glucuronidase. Neutral protease levels were higher (P = .066) at moderately to
      severely inflamed implant sites (Gingival Index of 2, 3) compared to mildly or
      noninflamed sites (Gingival Index of = 0, 1). Despite the small number (n = 5) of
      failing implants evaluated in this study, levels of neutrophil elastase,
      myeloperoxidase, and beta-glucuronidase were significantly higher (P < or = .001)
      around failing implants compared to successful implants. Neutral protease levels
      were also elevated around failing implants, but the difference was not
      statistically significant. Results of this study indicate that neutrophil
      elastase, myeloperoxidase, and beta-glucuronidase levels in GCF appear to be good
      candidates for study as risk markers of implant failure.

PMID- 8752554
TI  - Determination of cantilever length-anterior-posterior spread ratio assuming
      failure criteria to be the compromise of the prosthesis retaining screw
      prosthesis joint.
AB  - The maximum cantilever length-anterior-posterior spread (CL-AP) ratio is often
      used as an indication of the ability to cantilever in completely implant
      supported prostheses. The CL-AP ratios were determined assuming that failure
      occurs when the prosthesis retaining screw-prosthesis joint was compromised by
      either compressive (exceeding the pretorque value) or tensile (opening of the
      joint via plastic deformation) vertical forces using the Skalak model. Geometric
      arrangements of three, four, five, and six implants were analyzed. Force
      variables were 143, 200, and 400 N for the applied force, the pretorque value,
      and the joint tensile yield strength, respectively. The pretorque value was
      always exceeded before the yield strength. Allowable CL-AP ratios were (1) lower
      than those previously reported and (2) found to be 0.5 to 1.8, 0.7 to 1.6, 1.1 to
      1.7, and 1.8 for three, four, five, and six implants, respectively. Although
      implant distributions with the highest AP often provide adequate occlusion, the
      results of this study indicate that the use of a single CL-AP ratio alone is not
      necessarily a good indicator of the ability to cantilever.

PMID- 8752555
TI  - Eight-year clinical retrospective study of titanium plasma-sprayed and
      hydroxyapatite-coated cylinder implants.
AB  - A total of 1,202 press-fit cylinder implants were placed in 479 patients from
      March 1986 to March 1994. The patients' ages ranged from 14 to 88 years. The
      implants included 889 titanium plasma-sprayed implants and 313 hydroxyapatite
      coated implants. There were no statistically significant differences in the
      distribution of hydroxyapatite-coated and titanium plasma-sprayed implants based
      on implant location, type of restoration, age, and sex. Although differences in
      long-term success rates based on simple percentages were also not statistically
      significant, cumulative survival rates based on life table analysis up to 96
      months were 92.7% for titanium plasma-sprayed systems and 77.8% for
      hydroxyapatite-coated systems. Graphical interpretations of these data revealed
      interesting contrasts, including the timing and results of implant failure, which
      are discussed in detail.

PMID- 8752556
TI  - Factors affecting crestal bone loss with dental implants partially covered with a
      porous coating: a finite element analysis.
AB  - Limited crestal bone loss has been observed around dental implants partially
      covered with a porous coating. The results of a two-dimensional finite element
      analysis suggested that for this implant design, the observed crestal bone loss
      is the result of low stresses acting on bone around the uncoated superior region
      of the implant, causing disuse atrophy of bone. This finite element study
      investigated the effect on crestal bone loss of varying the design of the
      prosthesis connecting pairs of implants, the length of the uncoated region of the
      implant, and the friction at the noncoated coronal portion of the implant and
      adjacent host bone.

PMID- 8752557
TI  - Loaded and nonloaded titanium versus hydroxyapatite-coated threaded implants in
      the canine mandible.
AB  - A commercially pure titanium threaded implant was compared to a hydroxyapatite
      coated threaded implant of similar geometric design and dimensions in the canine
      model. Bilateral posterior implants supported fixed prostheses, and some implants
      in the same mandibles served as unloaded control implants. Implants were
      evaluated clinically, radiographically, and histomorphometrically at the light
      microscope level to detect any differences in bone response to loaded conditions.
      No statistically significant differences were found between the two implant
      designs under loaded or nonloaded conditions with regard to mobility, probing
      depth, percentage of osseointegration, and crestal bone position.

PMID- 8752558
TI  - A comparative study of one implant versus two replacing a single molar.
AB  - A comparative study between one and two Branemark implants replacing a single
      molar was conducted. Forty-seven individuals comprised two groups of 22 patients
      treated with one implant and 25 with two implants. A total of 72 implants were
      placed, 66 (92%) in the mandible and six (8%) in the maxilla. After the first
      year of function, the success rate was 99%, with only one implant lost. Between
      the second- and third-year follow-ups, 100% of the implants continued to function
      in the remaining 46 patients, giving a 3-year cumulative success rate of 99%. The
      marginal bone loss between 1 and 3 years of function was 0.10 mm (SD 0.20) for
      the group with one implant and 0.24 mm (SD 0.20) for the group with two implants.
      No changes were observed in the Sulcus Bleeding Index during the 3-year follow
      up. Prosthesis mobility or screw loosening was the most frequent complication and
      was predominant in the group using one implant (48%), but was substantially
      reduced in the group using two implants (8%). These mechanical problems, using
      one implant only, seem to be preventable using a stronger screw joint (CeraOne
      abutment). Precise centric occlusal contact was established and maintained over
      the study period, which was thought to contribute to the very high success rate
      for the single-implant-supported molars, despite their high degree of mechanical
      problems. This study suggests that implant-supported molars can be effective
      therapy, and the results confirm the biomechanical analysis that two implants
      provide more advantageous support than does one.

PMID- 8752559
TI  - Use of wide implants and double implants in the posterior jaw: a clinical report.
AB  - As experience with osseointegrated implants has grown, greater use has been made
      of placement in the posterior jaw. To reduce the risk of implant failure and
      increase the ability of posterior implants to tolerate the occlusal forces, it is
      beneficial to create a wider base either by using wider (eg, 5-mm) implants or by
      placing two or even three standard implants at one site. In the present series,
      unpaired 5-mm Nobelpharma implants were placed in 38 sites in the mandible and 21
      sites in the maxilla. All implants were uncovered and restored with ceramometal
      crowns, with follow-up ranging from 3 to 26 months (mean 16 months) postloading.
      Two implants in one patient failed and were replaced successfully at 14 months.
      At 20 sites, pairs of 5-mm implants were placed and restored, and with a loading
      period of 3 to 26 months (mean 14 months), all of these implants were successful.
      At 34 sites, a 5-mm implant was paired with a 3.75-mm or 4-mm implant. With a
      loading period of 3 to 24 months (mean 13 months), one implant 5 mm wide and 8 mm
      long failed and was replaced successfully at 13 months, and an implant 4 mm wide
      and 10 mm long failed and was not replaced. The failure rate for this group of
      implants therefore was 3%. Double 3.75-mm or 4-mm implants were placed at 149
      sites in the mandible and 13 sites in the maxilla. All of these double-root
      implants were uncovered and restored with ceramomental crowns. With follow-up
      ranging from 4 to 78 months (means 37 months) postloading, there were five
      implant failures in four patients, for a failure rate of 1.2%. The failure rate
      for all 5-mm implants was 2.3%, and that for all double implants was 1.6%. The
      use of either 5-mm or double implants necessitates changes in surgical technique,
      and both are highly dependent for their success on proper surgical execution.

PMID- 8752560
TI  - The TIME technique: a new method for localized alveolar ridge augmentation prior
      to placement of dental implants.
AB  - Sufficient bone volume is still considered the most important prerequisite for
      the osseointegration of dental implants. The TIME technique (autogenous bone
      grafting combined with stabilization using a titanium mesh) for localized
      alveolar ridge augmentation was evaluated in 20 patients who had insufficient
      bone volumes for the primary placement of dental implants. Different clinical
      recordings were evaluated at TIME stage 1 (augmentation surgery) and at TIME
      stage 2 (reentry surgery with mesh removal and simultaneous dental implant
      placement). In most patients, single- or extended-tooth gaps (up to four units)
      were augmented with autogenous bone harvested from the chin or retromolar area.
      With the exception of temporary disturbances of tooth sensibility, no morbidity
      at the donor sites was observed. In one patient, the stabilizing titanium
      micromesh had to be removed prematurely because of graft infection. At the
      reentry surgery, the bone grafts were found to be completely incorporated in 75%
      of the patients. In 15% of the patients, only minimal graft resorption was
      observed (less than 10% of the graft volume). Subsequently, 28 implants could be
      placed in 19 patients. The stabilizing titanium mesh was best suited for vertical
      ridge augmentations. Another feature of the mesh was the excellent tissue
      compatibility, with little clinical or histologic inflammation, even when the
      mesh had become exposed.

PMID- 8752562
TI  - Engineered bar design for a midface defect: a case report.
AB  - This case report describes the design process for engineering an implant-retained
      bar to support maxillary dental and facial prostheses for a patient missing his
      midface, including the maxilla, bilaterally. A computer-driven finite element
      analysis program was used to anticipate the forces and moments on each implant to
      distribute occlusal forces as evenly as possible. The implants, and later the
      prosthesis, were used to support the upper lip in the absence of bony support.
      The completed restorations greatly improved the patient's speech, eating, and
      appearance.

PMID- 8752561
TI  - The use of a provisional restoration in implant dentistry: a clinical report.
AB  - Provisional restorations in implant dentistry have rarely been considered an
      important stage in treatment. The definitive restoration is commonly fabricated
      in the laboratory with very little clinical input. The potential for error in the
      selection of abutments, framework design, appropriate vertical dimension of
      occlusion, occlusal profile, and finally the esthetic interpretation is
      significant. These static and dynamic variables can be identified clinically and
      communicated to the laboratory. It is suggested that all fixed detachable implant
      procedures incorporate a provisional phase to allow the diagnosis of static and
      dynamic clinical variables that determine the final design of the prosthesis.
      Implant restorations should be designed with a clinical basis that can be
      confirmed from a functional provisional restoration.

PMID- 8752563
TI  - [The clinical significance of the magnitude of esophageal dilatation in
      idiopathic achalasia].
AB  - The relationship between the diameter of the esophageal body and the clinical
      profile of the disease and response to treatment was analyzed in 151 patients
      with idiopathic achalasia by pneumatic dilation of the cardias. Of the 151
      patients, 46 presented an esophageal diameter < or = 3 cm (group I), 78 a
      diameter > 3 cm up to a maximum of 5 cm (group II) and 27 presented a diameter >
      5 cm (group III). The result of pneumatic dilatation of the cardias under
      endoscopic control was analyzed in 117 patients with a minimum follow up of one
      year after the last dilatation session. Of all the clinical parameters studied,
      significant statistical differences were only found in group III in respect to
      the time of symptom evolution and the presence of regurgitation. Manometric data
      in basal pressure of the esophageal body and in contraction wave width were lower
      in groups I and III, respectively. The remaining variables were similar in the
      three groups although group III showed a trend to older age and the frequency of
      pulmonary complications with lesser thoracic pain and registry of a strict
      pattern. Endoscopic pneumatic dilation carried out in all the cases was effective
      in 83% of the patients and was similar in the three study groups. The rate of
      complications (perforation) was also similar. The therapeutic efficacy of
      pneumatic dilatation was accompanied by a significant reduction in esophageal
      diameter. It was concluded that the increase in esophageal diameter in idiopathic
      achalasia is associated with chronological, clinical and functional parameters
      which suggest greater disease evolution but do not determine significant changes
      in the therapeutic response to endoscopic pneumatic dilatation.

PMID- 8752564
TI  - [The efficacy of excluding anti-HVC-positive donors by ELISA 2 in the prevention
      of posttransfusion hepatitis].
AB  - To assess the efficacy of blood donor screening with a second generation ELISA
      for the detection of anti HCV the incidence of post transfusion hepatitis was
      prospectively determined in 190 patients submitted to cardiovascular surgery. An
      increase greater than 100 U/l of transaminases of serum activity was detected in
      five patients (2.6%), being found in four patients at 3 months of the transfusion
      and in one patient at 6 months. Serologic markers for HAV, HBV, HCV, CMV and EBV
      were not identified in any of these cases of post transfusion hepatitis and it is
      therefore assumed that they may have been caused by an, as yet unidentified,
      agent. It is concluded that second generation ELISA screening for anti HCV is
      very effective in the prevention of post transfusion hepatitis C.

PMID- 8752565
TI  - [Ribavirin treatment in patients with chronic hepatitis C refractory to
      interferon-alpha].
AB  - Four patients with chronic hepatitis C who did not respond to treatment with
      alpha interferon were treated with oral ribavirin at a dose of 1.000-1.200 mg/day
      for 6 months. A marked, although transitory, decrease was observed in the
      transaminase values which returned to pre-treatment values on termination of the
      same. Normal transaminase values were only obtained at some point in the
      treatment in two patients. Ribavirin was well tolerated with very slight anemia
      being detected in all the cases. These results, which are superposable to those
      of other authors who have studied the effects of this antiviral agent in chronic
      hepatitis C, suggest that ribavirin may play a role in the treatment of this
      disease. Given the existing data, this role would be one of a drug associated
      with interferon with which it may have a synergic action rather than as a
      monotherapy.

PMID- 8752566
TI  - [Abdominal pseudotumor and Whipple's disease].
AB  - Whipple's disease is an uncommon systemic disease which most often affects the
      intestine but may involve any other organ. The case of a woman who consulted for
      weight loss, fever of unknown origin, cutaneous eruptions and increase in the
      abdominal perimeter is presented. The ascitic fluid showed exudate infected by E.
      coli suggesting spontaneous bacterial peritonitis associated with chronic liver
      disease. Antibiotic treatment and diuretics were administered after which
      abdominal exploration demonstrated the presence of a mesogastric mass.
      Echographic and tomographic studies were unable determine the origin of the mass
      with the final diagnosis being achieved by exploratory laparotomy and biopsy.

PMID- 8752567
TI  - [Digestive hemorrhage due to duodenal angiodysplasia in the periampullary area].
AB  - A case of digestive hemorrhage due to duodenal angiodysplasia at the level of the
      Vater papilla is presented. Diagnosis was achieved by analysis of the surgical
      resection sample.

PMID- 8752568
TI  - [Acute pancreatitis caused by valproic acid: apropos a case].
AB  - Acute pancreatitis is a rare, albeit severe, secondary effect of valproic acid
      which is probably due to an idiosyncratic reaction. Diagnosis is based on high
      clinical suspicion. A new case of pancreatitis by valproic acid an a review of
      the literature are presented. The authors suggest that strict clinical control of
      the patient be carried out and pancreatic enzymes be monitored on appearance of
      symptoms suggestive of this complication.

PMID- 8752569
TI  - [Leukocytoclastic vasculitis as the form of presentation of hepatocarcinoma].
AB  - The clinical case of a 45-years old patient with previous diagnosis of alcoholic
      cirrhosis who was admitted to study the appearance of a picture consisting in
      erythematoviolescent lesions in the lower limbs and advanced renal failure is
      presented. Anatomopathologic study of the cutaneous lesions suggested the
      diagnosis of leukocytoclastic vasculitis. This fact was of special clinical
      interest on having taken into consideration the cytologic demonstration of
      hepatocarcinoma superimposed to the established chronic liver disease of the
      patient. The rarity of leukocytoclastic vasculitis as the initial clinical
      manifestation of a hepatocarcinoma versus the most common forms of presentation
      is herein discussed.

PMID- 8752570
TI  - [The interferon treatment of hepatitis C in the liver transplant patient].

PMID- 8752571
TI  - [Immunohistochemistry and in situ hybridization in the identification of the
      hepatitis C virus in liver tissue].

PMID- 8752572
TI  - [Hepatitis C virus genotypes].

PMID- 8752573
TI  - [Gastric tuberculosis. A first case].

PMID- 8752574
TI  - [Pneumothorax secondary to the placement of a nasogastric tube in a patient with
      a decreased level of consciousness].

PMID- 8752575
TI  - Immunocytochemical visualization of the mGluR1a metabotropic glutamate receptor
      at synapses of corticothalamic terminals originating from area 17 of the rat.
AB  - Pre-embedding immunogold histochemistry was combined with Phaseolus vulgaris
      leucoagglutinin anterograde tract tracing in order to analyse the relationship
      between the subcellular localization of the GluR1a metabotropic glutamate
      receptors and the distribution of corticothalamic synapses in the dorsal lateral
      geniculate nucleus (dLGN) and the lateral posterior nucleus (LP) of the rat. The
      injection of the tracer into area 17 labelled two types of corticothalamic
      terminals: (i) the small boutons constituting the majority of the labelled fibres
      which form asymmetrical synapses both in the dLGN and LP; and (ii) the giant
      terminals typically participating in glomerulus-like synaptic arrangements and
      found exclusively in the lateral posterior nucleus. The small corticothalamic
      terminals often established synapses with mGluR1a-immunopositive dendrites, with
      immunometal particles concentrated at the periphery of their postsynaptic
      membranes. In contrast, the synapses formed by giant boutons in the lateral
      posterior nucleus were always mGluR1a-immunonegative. We conclude that the
      corticothalamic fibres forming the small synaptic terminals are the most likely
      candidates for the postulated mGluR-mediated modulation of visual information
      flow by corticothalamic feedback mechanisms.

PMID- 8752576
TI  - The effects of neonatal dorsal root section on the survival and dendritic
      development of lumbar motoneurons in the rat.
AB  - Peripheral nerve crush during the early neonatal period results in the death of a
      large proportion of affected motoneurons and abnormal dendritic development in
      those which survive. The present study reports the effects of neonatal dorsal
      root section on motoneurons supplying the extensor digitorum longus muscle of the
      rat. This lesion did not result in motoneuron death, but did disrupt subsequent
      dendritic development. In cells retrogradely labelled with cholera toxin subunit
      B conjugated to horseradish peroxidase, there was little change in adult
      dendritic morphology in the transverse plane, where abnormalities associated with
      loss of efferent contact and cell death have been found. However, there was a
      caudal expansion of the dendritic field, an effect seen following nerve crush but
      not after blockade of neuromuscular transmission alone. The results show that
      disruption of dorsal root sensory inputs alone can affect the dendritic
      development of motoneurons but does not cause their death. In conjunction with
      our earlier findings, it is clear that both afferent and efferent connections are
      required for normal dendritic development, and disruption of either has a
      characteristic effect on survival and dendritic morphology.

PMID- 8752577
TI  - A cholecystokinin-B receptor antagonist potentiates GABAergic and glycinergic
      inhibition in the nucleus of the solitary tract of the rat.
AB  - In both rodent and primate in vivo models, cholecystokininB (CCKB) antagonists
      such as PD134,308 have anxiolytic effects that may involve the potentiation of
      GABAergic transmission. We have investigated this interaction using exogenous
      application of GABA and whole cell patch recording techniques in neurons of the
      nucleus of the solitary tract (NTS) in brainstem slice preparations. In the
      presence of PD143,308 the magnitude of the GABA-evoked decrease in membrane input
      resistance was enhanced by 41.2 +/- 3.1% and the duration of the response was
      prolonged by 34.8 +/- 2.2%. Also, PD134, 308 potentiated glycine-evoked decreases
      in membrane input resistance, increasing the amplitude of the response by 62.8 +/
      4. 85 and prolonging the duration of the response by 23.5 +/- 3.6%. The effect
      of PD134,308 persisted in the presence of tetrodotoxin, after reversal of the
      transmembrane gradient of chloride ions and under conditions of exaggerated GABAA
      receptor desensitization. Our results demonstrate that at least part of the
      functional link between PD134,308 and the GABAA response occurs postsynaptically.

PMID- 8752578
TI  - Neurite outgrowth on non-permissive substrates in vitro is enhanced by ectopic
      expression of the neural adhesion molecule L1 by mouse astrocytes.
AB  - Axonal regrowth in the lesioned central nervous system (CNS) of adult mammals is,
      in part, prevented by non-permissive properties of glial cells and myelin. To
      test if ectopic expression of the neurite outgrowth promoting recognition
      molecule L1 will overcome these non-permissive influences and promote neurite
      outgrowth, L1 was expressed in astrocytes of transgenic mice using regulatory
      sequences of the glial fibrillary acidic protein (GFAP) gene. Northern blot
      analysis of different transgenic lines revealed different levels of
      transgenically expressed L1. Cultured astrocytes derived from transgenic animals
      displayed L1 immunoreactivity at the cell surface and in situ hybridization and
      immunocytochemical analysis of optic nerves from adult transgenic mice localized
      L1 expression to astrocytes. Expression of L1 protein by transgenic astrocytes
      was significantly upregulated in lesioned optic nerves. When mouse small
      cerebellar neurons or chick dorsal root ganglion neurons were cultured on
      cryosections of lesioned optic nerves or astrocyte monolayers from transgenic
      mice, respectively, neurite outgrowth was increased up to 400% on tissue sections
      and 50% on astrocytes compared with similar preparations from non-transgenic
      mice. The increase in neurite outgrowth on tissue sections or astrocyte
      monolayers from different transgenic lines was proportional to the different
      levels of L1 expression. Moreover, increased neurite outgrowth on these
      substrates was specifically inhibited by polyclonal L1 antibodies. In vivo,
      rescue of severed axons was enhanced in transgenic versus wild type animals,
      while regrowth of axons was slightly, but not significantly, increased. Together,
      our observations demonstrate that L1 promotes neurite outgrowth when expressed
      ectopically by astrocytes and that L1 is able to overcome, at least partially,
      the non-permissive substrate properties of differentiated CNS glial cells in
      vitro.

PMID- 8752579
TI  - Synergistic neurite-outgrowth promoting activity of two related axonal proteins,
      Bravo/Nr-CAM and G4/Ng-CAM in chicken retinal explants.
AB  - In the developing chicken retina, optic fibres migrating to the tectum express on
      their surfaces several cell adhesion molecules, including Bravo/Nr-CAM and G4/Nr
      CAM and G4/Ng-CAM. We have previously described differential distribution along
      the retinotectal projection and differential modulation by environmental cues for
      Bravo and G4 and here we further compare the characteristics of these
      immunoglobulin superfamily molecules. From day 6 of embryonic development (E6) to
      20 (E20), Bravo and G4 were found to coexist in the retinal optic fibre layer.
      However, while G4 staining was confined to that layer, as development proceeded
      Bravo staining spread to plexiform layers and some radial structures of the
      retina. G4 displayed a dose-dependent neurite-outgrowth promoting activity for E6
      retinal explants, while Bravo did not support neurite growth. Surprisingly, when
      the retinal explants were grown on mixtures of the two molecules, a much more
      vigorous growth of neurites was seen, revealing a synergistic effect. We propose
      that Bravo and G4, as well as other axonal surface molecules, affect axonal
      growth in different ways when they are present in combination than when they are
      alone.

PMID- 8752580
TI  - Reversible inhibitory effects of interferon-gamma and tumour necrosis factor
      alpha on oligodendroglial lineage cell proliferation and differentiation in
      vitro.
AB  - We have investigated the effects of the two prominent inflammatory cytokines,
      interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), on
      oligodendroglial lineage cell development and survival. Purified oligodendrocytes
      and oligodendrocyte precursors obtained from neonatal rat brain primary cultures
      were subcultured in a defined, serum-free medium and exposed to IFN-gamma (1-100
      U/ml, TNF-alpha (25-100 ng/ml) or both (100 U/ml and 50 ng/ml respectively) from
      day 1 to day 3 or from day 3 to day 6. While cell survival was not affected in
      any of the conditions tested, IFN-gamma dose-dependently inhibited [3H]thymidine
      or bromodeoxyuridine incorporation (by up to 50%) and the reduction of the
      tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide
      (MTT; by up to 33%). TNF-alpha synergized with IFN-gamma, but was ineffective by
      itself. Moreover, IFN-gamma totally antagonized the induction by basic fibroblast
      growth factor and platelet-derived growth factor of the proliferation of the
      oligodendroglial lineage cell population under study. IFN-gamma also blocked the
      differentiation of oligodendrocyte precursors, as evidenced by cell morphology,
      immunostaining for early and late differentiation markers (galactocerebroside and
      myelin basic protein respectively) and activity of ceramide galactosyl
      transferase. Again, the effect of IFN-gamma was potentiated by TNF-alpha, which
      was ineffective when tested alone. The inhibitory activity of IFN-gamma was
      rapidly reversible: 3 days after removal of the cytokine, administered from day 1
      to day 3, complete recovery of cll proliferation and differentiation could be
      documented. The cytokine-induced arrest in the expression of differentiation
      antigens was accompanied by perturbations in the expression of the corresponding
      mRNAs, revealed by a semiquantitative reverse transcription-polymerase chain
      reaction method. In particular, the message for myelin basic protein (and, in the
      case of treatment from days 3 to 6, also that for myelin associated glycoprotein)
      was decreased in cultures exposed to IFN-gamma, and further depressed in cultures
      treated with IFN-gamma and TNF-alpha, while TNF-alpha alone was ineffective. The
      above observations may help explain the role of IFN-gamma and TNF-alpha in the
      pathogenesis of inflammatory demyelinating diseases, in which increases in the
      levels of these substances have been described. In particular, in the case of
      multiple sclerosis, our results may bear on the problem of defective
      remyelination and are consistent with the frequent relapsing-remitting course of
      the disease.

PMID- 8752581
TI  - Peripheral, but not central, nervous system abnormalities are reversed by
      pancreatic islet transplantation in diabetic Lewis rats.
AB  - Neuroelectrophysiological recordings represent a non-invasive and reproducible
      method of detecting central and peripheral nervous system alterations in diabetes
      mellitus. In order to evaluate whether the normalization of metabolic control
      obtained by pancreatic islet transplantation could reverse diabetic
      neuroelectrophysiological alterations, or prevent further deterioration, we used
      an experimental model in which pancreatic islets (n = 1200) were injected into
      the portal vein of inbred Lewis rats (used as islet donors as well as
      recipients). Islets were injected 4 months after diabetes induction, since
      previous work had shown functional but not morphological damage at the nervous
      tissue level at this stage of the disease. Visual (V), brainstem auditory (BA)
      and somatosensory (S) evoked potentials (EPs) were measured in streptozotocin
      induced, islet-recipient diabetic rats (n = 7), streptozotocin-induced diabetic
      rats (n = 16) and non-diabetic control rats (n = 12). Metabolic parameters and
      electrophysiological recordings were evaluated before diabetes induction, before
      transplantation and 4 months later. After transplantation, glycaemic levels
      returned to normal values within 1 week and remained so until the end of the
      study, as confirmed by a normal oral glucose tolerance test and by an increase in
      body weight. Electrophysiological recordings were altered in diabetic animals
      before transplantation. Four months after transplantation EP recordings improved,
      with a detectable gradient from the peripheral to the central structures. SEPs
      were significantly improved in the peripheral tarsus-L6 tract and the L6-cortex
      tract (P < 0.005 and P < 0.01 versus diabetic rats) and were ameliorated without
      achieving statistical significance in the central L6-cortex tract. BAEP latency
      values tended to improve in transplanted rats, but the differences versus non
      transplanted diabetic animals failed to reach significance. VEP values remained
      clearly pathological and even deteriorated after transplantation. These results
      show that normalization of metabolic control by pancreatic islet transplantation
      can reverse some of the already established neuroelectrophysiological alterations
      at the peripheral nervous system level, but does not affect other alterations at
      the central nervous system level.

PMID- 8752582
TI  - Potentiated cAMP rise in metabotropically stimulated rat cultured astrocytes by a
      Ca2+-related A1/A2 adenosine receptor cooperation.
AB  - Adenosine agonists favoured an intracellular Ca2+ rise in cultured type 1
      astrocytes if the metabotropic glutamate receptors were concomitantly stimulated
      by (2S, 1's, 2's)-2-(carboxycyclopropyl)glycine (L-CCG-I; group II agonist),
      quisqualate (group I agonist) or 1-aminocyclopentane-trans-1, 3-dicarboxylic acid
      (t-ACPD; groupI/II agonist). Since the generation of a Ca2+ signal reflected a
      newly adopted adenosine A1 receptor action, we tested the possible consequence
      that the established opposing control of the cellular cAMP content by inhibitory
      A1 and stimulatory A2 receptor activation was also altered. During metabotropic
      receptor stimulation by LCCG-I, quisqualate or t-ACPD, the non-selective
      adenosine agonist 2-chloroadenosine (Cl-adenosine) caused a potentiated cAMP
      increase which markedly exceeded that produced by Cl-adenosine alone. This cAMP
      potentiation resulted from altered and Ca2+-dependent A1/A2 receptor cooperation.
      It was abolished by A1 receptor blockade and could not be achieved in the
      presence of t-ACPD by the A1 agonist R(-)N6-(2-phenylisopropyl)-adenosine or by
      the A2 agonist 5'-N-ethyl carboxyamidoadenosine alone, but obtained using their
      combination. The cAMP potentiation was blocked by intracellular Ca2+ chelation
      and the required A1 receptor action could be mimicked by a Ca2+ signal generated
      by the P2y receptor agonist adenosine 5'-(beta-thio)diphosphate. The results
      support the conclusion that nanomolar concentrations of adenosine may influence
      astrocyte reactions by stimulating Ca2+ and cAMP-dependent signalling cascade.

PMID- 8752583
TI  - Growth of callosal terminal arbors in primary visual areas of the cat.
AB  - In kittens ranging in age between postnatal day (P) 5 and P150, callosal axons
      originating near the 17/18 border were anterogradely labelled with biocytin and
      reconstructed from serial sections. At the end of the first postnatal week most
      of the axons begin to invade the cortex near the 17/18 border with multiple
      branches; some axons already span the grey matter up to layer 1. Branches tend to
      grow into the grey matter in loose bundles </=100 microm in diameter, separated
      by empty spaces of comparable width. In the following weeks additional branches
      are produced in the grey matter; this appears to blur the initial bundled
      distribution, although by the end of the first postnatal month the branches are
      distributed in discrete patches similar to the adult terminal columns. Although a
      few boutons (presumably synaptic boutons) are found in the white matter/subplate
      region at earlier ages, they appear in the grey matter from P12 onwards. Their
      number per axon increases with age, reaching adult values about the end of the
      first month. Subsequently the number of boutons continues to increase and remains
      above adult values at P50, P65 and P80; it then decreases, reaching adult levels
      by P150. During the first month boutons tend to be more numerous in the
      infragranular layers, but then the trend reverses in favour of the supragranular
      layers. In most cases, the distribution of boutons spares layer IV partially or
      completely. From the onset boutons are distributed in radial columns whose
      diameter increases with age. They maintain selective laminar and columnar
      distributions through the period of rapid and exuberant increase. These
      distributions do not appear to be sharpened further by the reduction in the
      number of boutons to adult levels. On the whole, callosal terminal arbors
      differentiate through stages of exuberant, albeit progressively constrained,
      growth involving both progressive and regressive events. Comparisons with
      previous work suggest that visual activity might finely shape the arbor, from the
      onset of synaptogenesis onwards.

PMID- 8752584
TI  - Activation of nucleotide receptors inhibits high-threshold calcium currents in
      NG108-15 neuronal hybrid cells.
AB  - A P2U (UTP-sensitive) nucleotide receptor has previously been cloned from NG108
      15 neuroblastoma x glioma hybrid cells and it has been shown that activation of
      this receptor inhibits the M-type K+-current. We now report that UTP also
      inhibits Ca2+-currents in differentiated NG108-15 cells, but probably through a
      different nucleotide receptor. UTP (100 microM) inhibited the peak of the high
      threshold current by 28.4 +/- 3.1% (n = 28) with no effect on the low-threshold
      current. Two components of high-threshold current were identified: one inhibited
      by 100 nM omega-conotoxin (CgTx) and one inhibited by 2 microM nifedipine and
      enhanced by 1 microM BAY K8644. UTP inhibited the former by 31.0 +/- 3.1%, with
      an IC50 of 2. 8 +/- 1.1 microM, and the latter 34.2 +/- 6.1% with an IC50 of 1.7
      +/- 1.3 microM. Pertussis toxin pretreatment prevented inhibition of the CgTx
      sensitive, nifedipine-resistant but not CgTx-resistant current. Inhibition was
      not prevented by intracellular BAPTA (20 mM) or cAMP (1mM). Effects of UTP on
      both currents were imitated by UDP, ATP, ADP, AP4A and ATPgammaS but weakly or
      not at all by 2-MeSATP, GTP, AMP-CPP or ITP. Since the receptors which inhibit
      Ca2+-currents are activated by ATP, it is suggested that they might mediate auto
      inhibition of transmitter release by ATP if present on purinergic nerve
      terminals. KEYWORDS: nucleotides, UTP, ATP, calcium currents, neuroblastoma cells

PMID- 8752585
TI  - Inability of rhesus monkey area V1 to discriminate between self-induced and
      externally induced retinal image slip.
AB  - Retinal image slip can result from an eye movement across a stationary object or
      alternatively from motion of the object while the eyes are stationary. The
      ability to discriminate between these two kinds of retinal image slip is
      necessary for the perception of a stable visual world. In order to determine if
      this ability is already present in monkey visual area V1, we asked if single V1
      units are able to differentiate between externally and self-induced retinal image
      slip. Externally induced retinal image slip was realized in the 'object motion'
      condition (OMC) by moving a behaviourally irrelevant visual stimulus ('object': a
      bar or a large random dot pattern) across the receptive field while the monkey
      fixated a small, stationary target. Conversely, self-induced retinal image slip
      of comparable size was evoked in the 'ego motion' condition (EMC) by asking the
      monkey to pursue the target, moving at the speed of the object in the OMC, while
      the object was kept stationary. We recorded 221 units from visual area V1, 51,
      (23%) of them directionally selective, and compared their responses to self
      induced and externally induced retinal image slip. Many of them seemed to give
      some preference to externally induced retinal image slip. However, on closer
      examination it became clear that this seeming preference could be attributed to
      the fact that oculomotor performance was less precise in the EMC than in the OMC,
      causing a larger deviation from the optimal retinal image trajectory in the EMC.
      We show that the impact of eye position errors can be eliminated by the use of a
      position-invariant stimulus, such as large-field random dot patterns. We then
      show that the impact of both eye position errors and deviation of eye velocity
      from target velocity in the EMC can be eliminated by moving the stimulus in a
      given OMC trial according to an inverted replica of the eye movement trajectory
      in the preceding EMC trial, guaranteeing identical retinal stimulation in the OMC
      and the EMC. If identical retinal stimulation was ensured, none of the V1 units
      tested was able to differentiate between externally and self-induced retinal
      image slip. We conclude that V1 does not contribute to the perception of a world
      which is stable despite eye movements.

PMID- 8752586
TI  - BDNF and NT-3, but not NGF, prevent axotomy-induced death of rat corticospinal
      neurons in vivo.
AB  - Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) have been
      identified as survival factors for adult axotomized rat corticospinal neurons
      (CSN) in vivo. Axotomy of corticospinal neurons at the level of the internal
      capsule induced death of 46% of the CSN within the first week after axotomy. The
      surviving population of CSN displayed severe atrophy with mean cross-sectional
      area 49% of their unlesioned contralateral counterparts 7 days after axotomy.
      Using in situ hybridization to assess the expression of the receptors for the
      family of neurotrophins, we found trkB and trkC but not trkA mRNA expression in
      CSN. Intraparenchymal application of BDNF or NT-3 at doses of 12 microg/day for 7
      days via an osmotic minipump fully prevented the axotomy-induced death of CSN.
      Interestingly, no neuronal atrophy was seen after BDNF application while NT-3 had
      only a partial effect on the size of the axotomized CSN. Nerve growth factor did
      not prevent death or cell atrophy, consistent with lack of trkA mRNA expression
      in these neurons. These findings show that BDNF and NT-3 are survival factors for
      adult rat CSN in vivo, and may contribute to the development of therapeutic
      strategies aiming at the prevention of CSN degeneration in human motor neuron
      diseases.

PMID- 8752587
TI  - Blockade of A2a adenosine receptors positively modulates turning behaviour and c
      Fos expression induced by D1 agonists in dopamine-denervated rats.
AB  - In rats with unilateral 6-hydroxydopamine lesions of the dopaminergic
      nigrostriatal pathway, administration of the A2a adenosine antagonist SCH 58261
      alone did not induce any motor asymmetry but strongly potentiated the
      contralateral turning behaviour induced by the dopamine D1 agonist SKF 38393. SCH
      58261 also increased the number of Fos-like positive nuclei induced by SKF 38393
      in the 6-hydroxydopamine-lesioned striatum. Intense potentiation of D1-dependent
      turning behaviour and c-Fos expression was also observed after administration of
      the A2a/A1 antagonist CGS 15943. Administration of the A1 adenosine receptor
      antagonist DPCPX induced a small potentiation of D1-mediated contralateral
      turning while c-Fos expression induced by SKF 38393 was not modified. The results
      suggest that endogenous adenosine acting on A2a receptors can exert an inhibitory
      influence on the functional expression of D1-mediated responses in dopamine
      denervated rats, and propose new possible therapeutic approaches in the treatment
      of Parkinson's disease.

PMID- 8752588
TI  - Differential long-lasting potentiation of the NMDA and non-NMDA synaptic currents
      induced by metabotropic and NMDA receptor coactivation in cerebellar granule
      cells.
AB  - Whole-cell patch-clamp recordings in rat cerebellar slices were used to
      investigate the effect of metabotropic glutamate receptor activation on mossy
      fibre-granule cell synaptic transmission. Transient application of 20 microM 1S,
      3R-aminocyclopentane-1, 3-dicarboxylic acid simultaneously with low-frequency
      NMDA receptor activation induced long-lasting non-decremental potentiation of
      both NMDA and non-NMDA receptor-mediated synaptic transmission. Potentiation
      could be prevented by application of the metabotropic glutamate receptor
      antagonist (+)-O-methyl-4-carboxyphenyl-glycine at 500 microM.
      Characteristically, NMDA potentiation was two to three times as large as non-NMDA
      current potentiation, occurred only in a slow subcomponent, and was voltage
      independent. This result demonstrates a pivotal role of NMDA receptors in the
      metabotropic potentiation of transmission, which may be important in regulating
      cerebellar information processing. KEYWORDS: cerebellum, LTP, metabotropic
      receptors, NMDA receptors, patch-clamp, rat

PMID- 8752589
TI  - The distribution of brain-derived neurotrophic factor and its receptor trkB in
      parvalbumin-containing neurons of the rat visual cortex.
AB  - We analysed the distribution of brain-derived neurotrophic factor (BNDNF) and its
      receptor trkB in the adult rat visual cortex, paying particular attention to a
      GABAergic neuronal subpopulation - the parvalbumin-positive cells. We found
      expression of trkB in the cell body and apical dendrite of pyramidal neurons and
      in the cell body of non-pyramidal neurons. Double labelling experiments revealed
      extensive colocalization of parvalbumin and trkB immunoreactivity in non
      pyramidal neurons. Interestingly, the trkB-positive pyramidal neurons appeared
      surrounded by parvalbumin-labelled boutons. The use of double
      immunohistochemistry and in situ hybridization histochemistry showed that
      parvalbumin-positive neurons express trkB mRNA. BDNF mRNA was found in several
      cells. Coexpression of BDNF mRNA and parvalbumin immunoreactivity was extremely
      rare. These data strongly suggest that BDNF synthesized by cortical neurons acts
      as a postsynaptically derived factor for parvalbumin-positive neurons in the
      adult rat visual cortex.

PMID- 8752591
TI  - Pre-exposure to subtoxic levels prevents kainic acid lesions in organotypic
      hippocampal slice cultures: effects of kainic acid on parvalbumin-immunoreactive
      neurons and expression of heat shock protein 72 following the induction of
      tolerance.
AB  - The effects of kainic acid on the survival of principal neurons and parvalbumin
      immunoreactive (PARV-IR) neurons, and on the expression of heat shock protein 72
      immunoreactivity (HSP72-IR) were investigated in organotypic hippocampal slice
      cultures. Untreated cultures displayed an organotypic organization and the
      development and morphology of PARV-IR neurons in the hippocampus paralleled that
      reported to occur in vivo, with the exception of the hilar region of the dentate
      gyrus which exhibited a marked lack of PARV-IR neurons. No constitutive
      expression of HSP72 was found in untreated cultures. The lesion of CA3 neurons
      and the reduction in numbers of PARV-IR neurons in both CA3 and CA1 after chronic
      exposure to 5 microM kainic acid were similar to those reported to occur in vivo.
      Exposure to 1 microM doses of kainic acid resulted in a widespread appearance of
      HSP72-IR and the induction of tolerance to a previously toxic dose of kainic
      acid. These results suggest the presence of endogenous neuroprotective
      mechanisms, activated by a stress response which induces HSP72, and is
      reminiscent of the induced tolerance reported to occur after a mild ischaemic
      insult.

PMID- 8752590
TI  - Calcium signalling in mouse Bergmann glial cells mediated by alpha1
      adrenoreceptors and H1 histamine receptors.
AB  - The presence of adrenergic and histaminergic receptors in Bergmann glial cells
      from cerebellar slices from mice aged 20-25 days was determined using fura-2 Ca2+
      microfluorimetry. To measure the cytoplasmic concentration of Ca2+ ([Ca2+]i),
      either individual cells were loaded with the Ca2+-sensitive probe fura-2 using
      the whole-cell patch-clamp technique or slices were incubated with a membrane
      permeable form of the dye (fura-2/AM) and the microfluorimetric system was
      focused on individual cells. The monoamines adrenalin and noradrenalin (0.1-10
      microM) and histamine (10-100 microM) triggered a transient increase in [Ca2+]i.
      The involvement of the alpha1-adrenoreceptor was inferred from the observations
      that monoamine-triggered [Ca2+]i responses were locked by the selective alpha1
      adreno-antagonist prazosin and were mimicked by the alpha1-adreno-agonist
      phenylephrine. The monoamine-induced [Ca2+]i signals were not affected by beta-
      and alpha2-adrenoreceptor antagonists (propranolol and yohimbine), and were not
      mimicked by beta- and alpha2-adrenoreceptor agonists (isoproterenol and
      clonidine). Histamine-induced [Ca2+]i responses demonstrated specific sensitivity
      to only H1 histamine receptor modulators. [Ca2+]i responses to monoamines and
      histamine did not require the presence of extracellular Ca2+ and they were
      blocked by preincubation of slices with thapsigargin (500 nM), indicating that
      the [Ca2+]i responses were recorded after application of aspartate, bradykinin,
      dopamine, GABA, glycine, oxytocin, serotonin, somatostatin, substance P, taurine
      or vasopressin. We conclude that cerebellar Bergmann glial cells are endowed with
      alpha1-adrenoreceptors and H1 histamine receptors which induce the generation of
      intracellular [Ca2+]i signals via activation of Ca2+ release from inositol-1,4,5
      trisphosphate-sensitive intracellular stores.

PMID- 8752592
TI  - BDNF down-regulates neurotrophin responsiveness, TrkB protein and TrkB mRNA
      levels in cultured rat hippocampal neurons.
AB  - Regulation of Trk receptors by their ligands, the neurotrophins, was investigated
      in dissociated cultures of embryonic day 18 rat hippocampal neurons. Cultures
      were exposed to brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3)
      or NT-4/5 for 24 h upon plating followed by factor washout. As determined by
      immunohistochemical staining and phosphotyrosine blotting, the functional
      responses to acute stimulation with BDNF, NT-3 and NT-4/5, including c-Fos
      induction and phosphorylation of Trk and extracellular signal-regulated kinase
      (ERK) proteins, were significantly decreased after 6 days in culture by prior
      exposure to BDNF. As determined by Western and Northern blot analysis
      respectively, there was a parallel down-regulation of TrkB protein as well as of
      trkB and trkC mRNA levels in BDNF-pretreated cultures. Exposure to NT-3 or NT-4/5
      at the same concentrations as BDNF did not down-regulate any of the measured
      cellular responses or TrkB protein and/or trkB and trkC mRNA levels. Regulation
      of hippocampal neuronal Trkb protein does not appear to be just a development
      phenomenon, as infusion of BDNF into the hippocampus of adult rats for 6 days
      produced an 80% decrease in levels of full-length TrkB protein. We thus show that
      exposure of hippocampal neurons to BDNF, both in culture and in the adult brain,
      results in down-regulation of TrkB. At least in vitro, this leads to long-term
      functional desensitization to BDNF, NT-3 and NT-4/5, as well as down-regulation
      of trkB and trkC mRNA.

PMID- 8752593
TI  - Lemniscal input to identified neurons of the central nucleus of mouse inferior
      colliculus: an intracellular brain slice study.
AB  - Intracellular recordings were performed in 34 neurons in the central nucleus of
      the inferior colliculus in brain slice preparations of the mouse. Sixteen neurons
      recorded were stained intracellularly by injection of biocytin and identified as
      multipolar. After electrical stimulation of the lateral lemniscus, 32 of 34
      neurons exhibited postsynaptic potentials (PSPs). Onset latencies of the PSPs
      were 5.0 +/- 2.8 ms (range 2-12 ms), presumably reflecting the lack of a
      significant monosynaptic input to most of the neurons recorded. An excitatory PSP
      (EPSP), often followed by a late inhibitory PSP (IPSP), was present in all
      neurons which received synaptic input. The IPSPs usually had a reversal potential
      positive to the cell's resting membrane potential, thus working as shunting
      inhibitors. Superfusion of the slice with the GABAA antagonist bicuculline
      resulted in blockade of the IPSP and pronounced prolongation of the EPSP. In 50%
      of these cases, paroxysmal depolarizing shifts were observed in the presence of
      bicuculline. Blocking the non-NMDA glutamate receptors with 6,7
      dinitroquinoxaline-2,3-dione resulted not only in the total disappearance of
      EPSPs but also of late IPSPs, indicating that the latter depend on the
      glutamatergic EPSPs. Furthermore, all neurons recorded must receive substantial
      innervation from sources within the inferior colliculus, together constituting a
      complex neuronal network in the inferior colliculus with an important role of the
      inhibitory neurotransmitter GABA in controlling network properties.

PMID- 8752594
TI  - GAP-43 mRNA in mouse motoneurons undergoing axonal sprouting in response to
      muscle paralysis of partial denervation.
AB  - To test the hypothesis that collateral sprouting of motoneurons can occur without
      the intervention of metabolic changes in the cell body, we examined the levels of
      growth-associated protein 43 (GAP-43) mRNA in mouse motoneurons induced to sprout
      by muscle inactivity (following marcaine or botulinum toxin treatment) or by
      partial denervation. GAP-43 mRNA was selected as an appropriate marker for cell
      body metabolic changes because it is expressed at low levels in mature
      motoneurons, but is strongly expressed during developmental or regenerative
      axonal growth in motoneurons. Sprouting motoneurons were identified by retrograde
      labelling with fluorescent tracers applied to the muscle in which sprouting
      occurred. Both a full-length cDNA probe and an oligonucleotide probe were used
      for in situ hybridization. We were unable to detect any significant increases in
      GAP-43 mRNA levels in fluorescent motoneurons after any treatment, except 4 days
      after partial denervation (but not at 2 or 8 days). This amounted to a 1.6-fold
      increase in signal level compared to control motoneurons, while presumed
      axotomized motoneurons in the same spinal cords displayed on average an 8. 7-fold
      increase. We conclude that collateral sprouting can occur in motoneurons without
      a detectable increase in cell body levels of GAP-43 mRNA. The modest increase
      observed in the 4-day partial denervation situation may be a response to the more
      vigorous and extensive nodal axonal sprouting occurring in these motoneurons. Our
      results do not deny a role for pre-existing GAP-43 in collateral sprouting, but
      support the hypothesis that sprouting can occur in motoneurons without
      necessarily requiring increase GAP-43 mRNA levels in the cell body.

PMID- 8752595
TI  - Glial cell line-derived neurotrophic factor: the lateral cerebral ventricle as a
      site of administration for stimulation of the substantia nigra dopamine system in
      rats.
AB  - The direct application of recombinant human glial cell line-derived neurotrophic
      factor (rhGDNF) to the deep structures of the nigrostriatum has been shown
      previously to augment dopamine function and inhibit loss of substantia nigra
      neurons in rodent models of Parkinson's disease. The present studies were
      designed to determine whether administration of rhGDNF into the lateral
      ventricle, a more clinically accessible intracranial target, is capable of
      augmenting dopamine function of the nigrostriatal pathway in normal rats. Single
      bolus intracerebroventricular (i.c.v) injections of rhGDNF increased locomotor
      activity and decreased food and water consumption and body weight gain in a dose
      dependent manner. rhGDNF increased concentrations of dopamine and dopamine
      metabolites in the substantia nigra, ventral tegmental area and hypothalamus, but
      had no significant effects in the striatum. rhGDNF had no effect on striatal or
      substantia nigral serotonin (5-HT) and 5-hydroxyindoleacetic acid levels, but
      these levels were significantly increased in the ventral tegmental area and
      hypothalamus respectively. The augmentation of the dopamine and 5-HT systems was
      detected 2 weeks but not 3 days or 6 weeks after rhGDNF administration. After a
      repeat injection of i.c.v rhGDNF (6 weeks after the initial injection),
      substantia nigral dopamine, 5-HIAA and noradrenalin levels were increased. These
      results indicate that i.c. v administration of rhGDNF has an influence on adult
      rat dopamine neurons. This route of administration may be useful for stimulating
      dopamine neurons in Parkinson's disease.

PMID- 8752597
TI  - Diversity of postsynaptic amplitude and failure probability of unitary excitatory
      synapses between CA3 and CA1 cells in the rat hippocampus.
AB  - Different CA3 cells may have dissimilar effects on a CA1 pyramidal cell. In order
      to test this idea, we studied the amplitude distribution of excitatory
      postsynaptic currents (EPSCs) in response to weak electrical stimulation of
      presynaptic axons in the rat hippocampal slice. We accepted the response
      populations as representative for the effect of, in most cases, a single axon
      when the EPSCs appeared at a certain threshold stimulation strength, with the
      subsequent lack of increase in amplitude with further stimulation increase. By
      comparing the EPSC amplitude distributions obtained from different synaptic
      inputs to the same CA1 cell, we found differences in the failure probability and
      the EPSC amplitude, each of which contributed to differences in the mean response
      amplitude. We conclude that not only the number but also the specific subset of
      active CA3 cells is important for the synaptically driven discharge of a given
      CA1 cell.

PMID- 8752596
TI  - The extraneuronal transporter for monoamine transmitters exists in cells derived
      from human central nervous system glia.
AB  - From studies on sympathetically innervated peripheral tissues it is well known
      that both neuronal and non-neuronal transport systems contribute to the
      inactivation of released monoamine transmitters. The close proximity between
      synapses and glia cell processes in the CNS leads to the so far unresolved
      question whether non-neuronal transporters are involved in the inactivation of
      centrally released monamine transmitters such as noradrenaline, dopamine and 5
      hydroxytryptamine. 1-Methyl-4-phenylpyridinium (MPP+) is a prototypical substrate
      of the extraneuronal monoamine transporter (uptake2). [3H]MPP+ was found to
      accumulate in various human glioma cell lines. [3H]MPP+ transport was
      characterized in more detail in HTZ146 human glioma cells. The Ki values of
      various compounds for the inhibition of initial rates of [3H]MPP+ transport into
      HTZ146 cells were closely correlated with known Ki values for the inhibition of
      the extraneuronal monoamine transporter (P < 0.01, r = 0.991, n = 7). The rank
      order of inhibitory potencies was decynium 22 > corticosterone > cyanine 863 > O
      methylisoprenaline > quinine > clonidine > quinidine. [3H]MPP+ accumulation was
      investigated not only in various CNS tumour cell lines but also in primary
      cultures of human astrocytes and rat cerebral cortex slices. In all tested
      experimental systems, accumulation was sensitive to cyanine-related inhibitors of
      the extraneuronal monamine transporter. These findings suggest that the
      extraneuronal monamine transporter exists in glia cells. Furthermore, it was
      shown that MPP+ is able to make use of the extraneuronal monoamine transporter
      not only to enter but also to leave glia cells. This finding suggests that the
      extraneuronal monoamine transporter may play a key role in the mechanism of 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity.

PMID- 8752598
TI  - Naturally occurring (programmed) and radiation-induced apoptosis are associated
      with selective c-Jun expression in the developing rat brain.
AB  - Expression of the different members of transcription factors Fos and Jun was
      examined in the developing rat brain. Constitutive expression of c-Fos, Fos
      related antigens, Jun B and Jun D, as revealed with immunohistochemistry, is
      higher and more widely distributed in the developing rat brain than in the adult.
      Selective strong c-Jun expression is observed in the cytoplasm and nuclei of
      apoptotic cells during the whole process of naturally occurring (programmed) cell
      death. Cells expressing strong c-Jun immunoreactivity are undetermined cells,
      neurons and astrocytes. Selective c-Jun expression is also observed following
      ionizing radiation in rats aged 3 days. Induction of c-jun mRNA, as revealed with
      in situ hybridization, occurs between 5 and 15 min following gamma-irradiation.
      Strong c-Jun protein expression appears at 2 h, peaks at 6 h and decreases
      thereafter to reach normal levels 48 h after gamma-ray exposure. Strong c-Jun
      protein expression is coincidental with endonuclease activation, as revealed with
      the method of in situ labelling of nuclear DNA fragmentation, and is restricted
      to apoptotic cells. Cycloheximide injection at the time of irradiation blocks c
      Jun expression, indicating that c-Jun immunoreactivity is attributable to de novo
      protein synthesis. These observations demonstrate in vivo selective strong c-Jun
      expression associated with programmed cell death and ionizing radiation-induced
      apoptosis in the developing rat brain.

PMID- 8752599
TI  - Trimeric G proteins control regulated exocytosis in bovine chromaffin cells:
      sequential involvement of Go associated with secretory granules and Gi3 bound to
      the plasma membrane.
AB  - Regulated secretion requires both calcium and MgATP. Studies in diverse secretory
      systems indicate that ATP is required to prime the exocytotic apparatus whereas
      Ca2+ triggers the final ATP-independent fusion event. In this paper, we examine
      the possible role of trimeric G proteins in these two steps of exocytosis in
      chromaffin cells. We show that in the presence of low concentrations of Mg2+,
      mastoparan selectively stimulates G proteins associated with purified chromaffin
      granule membranes. Under similar conditions in permeabilized chromaffin cells,
      mastoparan inhibits ATP-dependent secretion but is unable to trigger ATP
      independent release. This inhibitory effect of mastoparan on secretion was
      specifically reversed by anti-Galphao antibodies and a synthetic peptide
      corresponding to the carboxyl terminus of Galphao. In contrast, mastoparan
      required millimolar Mg2+ for the activation of plasma membrane-bound G proteins
      and stimulation of ATP-independent secretion in permeabilized chromaffin cells.
      The latter effect was completely inhibited by anti-Galphai3. By confocal
      immunofluorescence and immunoreplica analysis, we provide evidence that in
      chromaffin cells Go is preferentially associated with secretory granules, while
      Gi3 is essentially present on the plasma membrane. Our findings suggest that
      these two trimeric G proteins act in series in the exocytotic pathway in
      chromaffin cells: a secretory granule-associated Go protein controls the ATP
      dependent priming reaction, whereas a plasma membrane-bound Gi3 protein is
      involved in the late calcium-dependent fusion step, which does not require ATP.

PMID- 8752600
TI  - Effects of thyrotropin-releasing hormone on GABAergic synaptic transmission of
      the rat hippocampus.
AB  - The effect of thyrotropin-releasing hormone (TRH), a neuropeptide physiologically
      present in the mammalian hippocampus, on spontaneous, miniature and evoked
      GABAergic postsynaptic currents was investigated using whole-cell patch-clamp
      recording from pyramidal cells and interneurons of the rat hippocampal thin slice
      preparation. Bath application of 10 microM TRH induced an increase in the
      frequency of spontaneous postsynaptic currents from 1.07 +/- 0.68 to 3.16 +/-
      0.73 Hz in pyramidal neurons and interneurons of the stratum lacunosum-moleculare
      (SL-M). In tetrodotoxin solution TRH did not change miniature postsynaptic
      currents. Application of TRH to minislices containing only the CA1 region still
      produced an increase in the spontaneous postsynaptic current frequency,
      indicative of an action by TRH upon a GABAergic circuitry. Paired recordings from
      one pyramidal cell and one stratum lacunosum moleculare interneuron displayed
      synchronous events whose frequency rose after TRH application, suggestive of a
      common, TRH-sensitive input. In a small subset of cells TRH induced the
      appearance of highly rhythmic large postsynaptic currents at a frequency of
      approximately 2 Hz, as confirmed by autocorrelation analysis. Postsynaptic
      currents electrically evoked by focal stimulation of stratum lacunosum-moleculare
      were depressed from 90 +/- 27 to 44 +/- 15 pA after application of TRH. This
      phenomenon was solely due to an increase in the number of synaptic failures. It
      is proposed that the effect of TRH on the GABAergic system was primarily exerted
      on a subset of interneurons controlling the activity of pyramidal cells as well
      as stratum lacunosum-moleuclare interneurons.

PMID- 8752601
TI  - Noradrenalin enhances the activity of cochlear nucleus neurons in the rat.
AB  - The cochlear nucleus of rats is heavily innervated by noradrenergic fibres from
      the locus coeruleus. The physiological meaning of this innervation is poorly
      understood. Therefore, iontophoretically applied noradrenalin was tested on
      single neurons of the cochlear nucleus in urethane-anaesthetized rats.
      Iontophoresis of noradrenalin had a dual effect. During application noradrenalin
      led to moderate inhibition of tone-evoked activity in 37% of the tested neurons.
      In contrast, approximately 20-30 s after the onset of iontophoresis a long
      lasting increase in discharge activity was found in most neurons. Data from
      iontophoresis of the alpha1-receptor agonist phenylephrine and the alpha2
      receptor agonist clonidine suggest that the fast moderate inhibition is mediated
      by alpha2-receptors while the pronounced long-lasting elevated neuronal firing is
      mediated by alpha1-receptors. However, these data do not exclude the possibility
      that part of the response to noradrenalin is also mediated by beta-receptors.
      Electrical stimulation of the locus coeruleus resulted in an increase in
      discharge activity comparable with iontophoresis of noradrenalin or
      phenylephrine. Thus, activation of the locus coeruleus predominantly increases
      spontaneous and tone-evoked neuronal firing in the cochlear nucleus of the rat.
      This alpha-receptor-mediated enhanced discharge activity may serve to increase
      the sensitivity of acoustic processing mechanisms or to lower the threshold for
      short-latency acoustic reflexes.

PMID- 8752603
TI  - The chemotactic attraction of human sperms to the oocyte: a maturing concept.

PMID- 8752602
TI  - Heterotopic pregnancy after ovulation induction and assisted reproductive
      technologies: a literature review from 1971 to 1993.
AB  - OBJECTIVE: To review and analyze records on heterotopic pregnancy occurring after
      ovulation induction and assisted reproductive technologies. DATA IDENTIFICATION:
      Case reports in the English literature related to the topic were identified
      through a computerized bibliography search up to December 1993. CONCLUSIONS: The
      incidence of heterotopic pregnancies increased in recent years because of the
      escalating use of new reproductive technologies in infertile patients and has
      stabilized at approximately 1:100 pregnancies with these procedures. The main
      reasons for development of such a condition in these patients are past tubal or
      pelvic disease and multiple ovulations or multiple ET. Progress has been made in
      diagnosis of heterotopic pregnancy during the last two decades, mainly because of
      development of ultrasonographic techniques, especially transvaginal
      ultrasonography. Treatment of heterotopic pregnancy should be prompt to avoid
      maternal morbidity and mortality from extensive intraperitoneal bleeding. No
      increased intrauterine fetal mortality due to hemoperitoneum has been proven in
      the present review, except in advanced cornual pregnancies. More experience is
      needed for application of new treatment modalities such as salpingocentesis,
      which are used successfully for ectopic pregnancy, in treatment of heterotopic
      pregnancy. With early diagnosis and skillful treatment, the outcome of the
      intrauterine pregnancy is favorable and its survival rate should increase in the
      future.

PMID- 8752604
TI  - Moments in the life of Patrick Steptoe.

PMID- 8752605
TI  - Elevated concentration and biologic activity of monocyte chemotactic protein-1 in
      the peritoneal fluid of patients with endometriosis.
AB  - OBJECTIVE: To estimate the concentration and the biologic activity of monocyte
      chemotactic protein-1 (MCP-1) in the peritoneal fluid (PF) of women with and
      without endometriosis. DESIGN: A case control study was conducted. SETTING:
      Gynecology clinic and Laboratories of endocrinology of reproduction and
      immunology. PATIENTS: Women presenting for infertility, pelvic pain, or tubal
      ligation in which endometriosis was diagnosed at laparoscopy (n = 36) and normal
      fertile controls presenting for tubal ligation (n = 21). INTERVENTIONS:
      Collection of PF via laparoscopy. MAIN OUTCOME MEASURES: Determination of PF
      concentrations of MCP-1 by an ELISA and evaluation of its monocyte chemotactic
      activity using a human hystiocytic cell line (U937). RESULTS. The concentration
      of MCP-1 (median, range of values) was increased in the PF of endometriosis
      patients (283, 0 to 1,930 pg/mL; conversion factor to SI unit, 0.155) compared
      with the control group (140, 0 to 435 pg/mL). The most significant elevation of
      MCP-1 levels was found in the stage II of the disease (371, 200 to 1,930 pg/mL).
      An increased chemotactic activity for monocytes (mean number of migrating
      cells/mm2 +/- SD) also was found in stages I (1,460 +/- 312) and II (1,541 +/-
      336) of the disease when compared with fertile controls (393 +/- 56). Forty
      percent to 53% of this activity was inhibited in the presence of an antibody
      specific to MCP-1. CONCLUSIONS: These observations are consistent with previous
      data indicating increased leukocyte chemotaxis in the PF of patients with
      endometriosis and suggest that MCP-1 may play a relevant role in the peritoneal
      inflammatory reaction associated with the disease.

PMID- 8752606
TI  - Frequency of factors associated with habitual abortion in 197 couples.
AB  - OBJECTIVE: To determine the frequency of factors associated with habitual
      abortion in 197 couples. DESIGN: Prospective cohort study. SETTING: The British
      Columbia Recurrent Pregnancy Loss Program, located in a tertiary care academic
      center. INTERVENTIONS: Diagnostic screening protocol. MAIN OUTCOME MEASURES:
      Genetic, endocrine, infectious, anatomical, and autoimmune factors associated
      with habitual abortion. RESULTS: A structural genetic factor was identified in
      3.5% of the couples. An endocrine factor, including luteal phase deficiency and
      hypothyroidism, was identified in 20% and an infectious factor was identified in
      0.5% of the couples. An anatomical factor, including various mullerian tract
      anomalies and severe intrauterine adhesions, was found in 16% and an autoimmune
      factor, including the antiphospholipid antibody syndrome and the undifferentiated
      connective tissue syndrome, was identified in 20% of the couples. Eighty-four
      couples who completed the diagnostic screening protocol were classified as having
      unexplained habitual abortion. Of these 84 couples, 65% were subclassified as
      primary, 27% were subclassified as secondary, and 7% had unclassified unexplained
      habitual abortion. CONCLUSIONS: This large-scale study identified genetic,
      endocrine, infectious, anatomical, or autoimmune factors in approximately 60% of
      couples with habitual abortion.

PMID- 8752607
TI  - Complications of laparoscopy--operative and diagnostic.
AB  - OBJECTIVE: To assess the characteristics and rates of complications for operative
      laparoscopy and diagnostic laparoscopy. DESIGN: Retrospective review. SETTING:
      Tertiary-care university hospital. PATIENTS: Two thousand three hundred twenty
      four patients undergoing operative laparoscopy or diagnostic laparoscopy.
      INTERVENTIONS: Operative laparoscopy including lysis of adhesions, tubal surgery,
      ovarian surgery, uterine surgery, or destruction of endometriosis. MAIN OUTCOME
      MEASURES: Complication rates for operative and diagnostic laparoscopies were
      tabulated and compared. RESULTS: The overall major complication rate for this
      series of 2,324 laparoscopies was 0.22%. There were five major and 15 minor
      complications. In the operative laparoscopy group, there were more complications
      from Veress needle and trocar insertion (n = 15) than from the actual operative
      procedures (n = 3). There were more total complications in the operative
      laparoscopy group (n = 18) than in the diagnostic laparoscopy group (n = 3).
      CONCLUSION: Operative laparoscopy is efficacious for a variety of gynecologic
      surgical procedures.

PMID- 8752608
TI  - Prospective study showing that antisperm antibodies are not associated with
      pregnancy losses.
AB  - OBJECTIVE: To obtain prospective data on the relationship between presence of
      antisperm antibodies in maternal sera and first trimester pregnancy losses.
      DESIGN: First trimester sera obtained from diabetic and nondiabetic women
      recruited within 21 days of conception were analyzed using the indirect
      immunobead test for immunoglobulin (Ig)G, IgA, and IgM antisperm antibodies.
      Regional binding also was considered: sperm head, midpiece, and sperm tail.
      Results were correlated with pregnancy outcome. SETTING: Five university centers.
      PATIENTS: One hundred eleven women who experienced pregnancy loss (55 diabetic;
      56 nondiabetic) were matched 2:1 with 104 diabetic and 116 nondiabetic women
      (controls) who subsequently had a normal liveborn infant. INTERVENTION: None.
      MAIN OUTCOME MEASURE: Pregnancy outcome (spontaneous abortion, liveborn)
      correlated with presence or absence of antisperm antibodies. RESULTS: Analyzing
      samples without knowledge of clinical status, no differences were observed with
      respect to IgG, IgA, and IgM binding when a positive test was defined as 50% of
      sperm showing antibody binding. Likewise, no association was found for IgG and
      IgM antisperm antibodies at 20% binding. The only positive finding was observed
      for IgA antisperm antibodies at 20% binding (Fisher's Exact test). This one
      positive finding merely could reflect multiple comparisons. No significant
      differences between groups were observed when analysis was stratified according
      to location of antibody binding (head, midpiece, tail tip, entire sperm). When
      the sample was stratified into those having and not having a prior loss, a
      relationship between antisperm antibodies and pregnancy loss still was not
      evident. CONCLUSION: Further work is necessary to determine whether IgA antisperm
      antibodies truly are associated with pregnancy loss or whether antisperm
      antibodies play any role in repetitive aborters. Findings in this study suggest
      that antisperm antibodies do not play a major role in pregnancy loss.

PMID- 8752609
TI  - Immediate postpartum insertion of the norplant contraceptive device.
AB  - OBJECTIVE: To determine the safety and efficacy of Norplant (Wyeth-Ayerst
      Laboratories, Philadelphia, PA) insertion immediately postpartum. DESIGN:
      Prospective study of 14 women receiving Norplant immediately postpartum compared
      with controls (n = 6) having a bilateral tubal ligation. Subjects were followed
      for 3 months postpartum, and data were analyzed by analysis of variance and chi2.
      SETTING: Academic Health Sciences Center. PATIENTS: Female subjects 18 to 35
      years old who had an uncomplicated term pregnancy, normal spontaneous vaginal
      delivery, and did not breast-feed. INTERVENTION: A brief interview, physical
      exam, and blood and urine samples were evaluated during a 12-week postpartum
      period. MAIN OUTCOME MEASURES: Major complaints, serum chemistry panels,
      hematologic and coagulative measures, serum E2, P, levonorgestrel, PRL, LH, FSH,
      and urinary estrone-3 conjugates and pregnanediol-3-glucuronide concentrations.
      RESULTS: Serum levonorgestrel peaked at approximately 2,000 pg/mL (6,400 pmol/L)
      during the 1st week after Norplant insertion, declining to approximately 250
      pg/mL (800 pmol/L) by the 8th week. Significant differences between Norplant and
      control groups included bleeding irregularities, headaches, alopecia, and
      abdominal discomfort. Serum electrolytes, metabolic markers, and blood components
      were within normal limits. Serum E2, P, and urinary steriod biomarkers indicated
      that steroid secretion was suppressed severely in the Norplant group compared
      with controls who exhibited normal postpartum ovarian activity. CONCLUSION:
      Norplant inserted immediately postpartum appears to be a safe and effective
      method of contraception. However, the long-term hypoestrogenic state and
      contraceptive efficacy beyond the 3-month postpartum period as observed in this
      study are concerns that need further clinical evaluation.

PMID- 8752610
TI  - Efficacy of selection criteria for ovarian reserve screening using the clomiphene
      citrate challenge test in a tertiary fertility center population.
AB  - OBJECTIVE: To examine selection criteria for ovarian reserve screening. DESIGN:
      Retrospective study. PATIENTS: Two hundred nineteen women underwent testing for
      ovarian reserve for woman's age > 35 years, any age with unexplained infertility,
      one ovary, or a poor response to hMG. INTERVENTIONS: Clomiphene citrate challenge
      test. MAIN OUTCOME MEASURES: Frequency of abnormal ovarian reserve screening,
      menstrual cycle parameters, response to hMG, and pregnancy outcome by screening
      criteria. RESULTS: One hundred eighty-four (84.0%) women had a normal ovarian
      reserve screening test; 35 (16.0%) had an abnormal ovarian reserve screening
      test. Twenty-six had abnormal ovarian reserve screening when screened by age, 14
      for unexplained infertility, 5 for poor response to hMG, and 6 for one ovary.
      Fifteen women with abnormal ovarian reserve screening had more than one
      indication for screening. For women attempting pregnancy (n = 182), 49 of 148
      (33.1%) with normal ovarian reserve screening became pregnant compared with 2 of
      34 (5.9%) with abnormal ovarian reserve screening. Within each screening
      category, women with abnormal ovarian reserve had menstrual cycle parameters
      associated with a short follicular phase, required more hMG, and responded poorly
      to hMG. CONCLUSIONS: One of six women undergoing ovarian reserve screening had an
      abnormal test, which was associated a poor reproductive outcome. Age was the most
      important single criteria. Selected ovarian reserve screening is simple and
      inexpensive and should be offered to all fertility patients meeting the specific
      screening criteria listed above.

PMID- 8752611
TI  - Pituitary function is altered during the same cycle in women with polycystic
      ovary syndrome treated with continuous or cyclic oral contraceptives or a
      gonadotropin-releasing hormone agonist.
AB  - OBJECTIVE: To determine if continuous oral contraceptive (OC) therapy was
      superior to a cyclic regimen in achieving persistent pituitary suppression of LH
      in patients with polycystic ovary syndrome (PCOS). DESIGN: Fourteen women (ages
      16 to 41 years) with PCOS received one of three treatment groups: continuous OC
      therapy (30 micrograms ethinyl E2 plus 150 micrograms desogestrel), cyclic OC
      therapy, or monthly injections of a GnRH agonist (GnRH-a, leuprolide acetate
      depot 3.75 mg) for 3 months. Basal hormone levels were obtained before initiating
      therapy, on days 15 to 17 of the 3rd month of treatment (study 1) and again on
      days 26 to 28 of the 3rd month (study 2). A GnRH stimulation test was also
      performed during study 1 and study 2. RESULTS: After 3 months of treatment, LH
      levels were decreased significantly in all groups with less effective suppression
      observed in the cyclic OC group compared with the continuous OC or GnRH-a groups.
      A significant rise in LH was found only in the cyclic OC group after 5 to 7 days
      of placebo treatment (study 1 versus study 2). An increase in T was also observed
      in the cyclic OC group during study 2, whereas the continuous OC and GnRH-a
      groups showed continued inhibition of T levels. Although there was no significant
      difference in LH area under the curve (AUC) measurements after GnRH stimulation
      in study 1 versus study 2, the LH AUC was significantly greater in both studies
      in the cyclic OC group compared with the continuous OC or GnRH-a groups.
      CONCLUSIONS: Increased LH secretion during the week of placebo in the cyclic OC
      group was associated with a concomitant increase in T. The striking rise in LH
      secretion after GnRH stimulation in the cyclic OC group may represent increased
      pituitary sensitivity in patients receiving cyclic OCs regardless of the phase of
      the treatment cycle, perhaps secondary to increased pituitary stores of LH in
      these women.

PMID- 8752612
TI  - Finasteride in the treatment of hirsutism: new therapeutic perspectives.
AB  - OBJECTIVE: To determine of the clinical and hormonal effects of finasteride
      (Proscar; Merck, Sharp, and Dohme, Rahway, NJ) in the treatment of idiopathic
      hirsutism and hirsutism in patients with polycystic ovary syndrome (PCOS).
      DESIGN: Controlled clinical study. SETTING: Istitute of Obstetrics and
      Gynecology, University of Naples "Federico II." PATIENTS: Ten women affected by
      idiopathic hirsutism and 15 women with PCOS. INTERVENTIONS: Finasteride was
      administered orally at a daily dose of 5 mg for a period of 6 months. MAIN
      OUTCOME MEASURES: Rating of hirsutism with the Ferriman-Gallwey method; serum
      androgen assays. RESULTS: Finasteride produced a reduction in the average
      hirsutism scores ( > 50% in all patients), whereas no change was observed in
      serum T, androstenedione, and DHEAS levels. A significant reduction was measured
      in serum dihydrotestosterone and 3 alpha, 17 beta-androstenediol glucuronide
      levels. CONCLUSIONS: This study demonstrates that symptomatic hirsutism has to be
      considered as a skin disease associated with the increased activity of the 5
      alpha-reductase. It also indicates that the selective 5 alpha-reductase
      inhibitor, finasteride, is very effective and well tolerated in the treatment of
      both idiopathic hirsutism and of hirsutism in patients with PCOS.

PMID- 8752613
TI  - Characterization of intraperitoneal cytokines and nitrites in women with severe
      ovarian hyperstimulation syndrome.
AB  - OBJECTIVE: To assess the potential involvement of cytokines and nitrites in the
      hyperpermeability characterizing the ovarian hyperstimulation syndrome (OHSS).
      DESIGN: A controlled clinical study comparing peritoneal fluid (PF) from patients
      with severe OHSS and from non-OHSS controls. SETTING: Women hospitalized with
      severe OHSS in three tertiary medical centers. PATIENTS: Twelve patients with
      severe OHSS necessitating paracentesis and 20 non-OHSS controls. INTERVENTIONS:
      The criteria for ultrasound-guided paracentesis were tense ascites, hydrothorax,
      hemoconcentration, or oliguria. MAIN OUTCOME MEASURES: Interleukin (IL) 1 beta IL
      1 receptor agonist, IL-2, IL-6, IL-8, and tumor necrosis factor alpha (TNF alpha)
      levels in PF were assayed by ELISA; nitrites were measured by the "Griess"
      reaction. Estradiol and P were determined by RIA. RESULTS: Ovarian
      hyperstimulation syndrome patients had significantly higher PF IL-6 (3,523 versus
      30 pg/mL), TNF alpha (14 versus 4.2 pg/mL), and IL-8 (1,695 versus 900 pg/mL). In
      the serum, only IL-6 levels were significantly higher (375 versus 11 pg/mL).
      Conversely, nitrite levels were significantly lower in PF of OHSS patients (0.5
      versus 34 nmol/mL). Interleukin 1 levels were higher and IL-1 receptor antagonist
      levels were lower in OHSS patients, suggesting potentially increased biologic
      potency of IL-1. CONCLUSION: These findings suggest that these substances could
      be involved in mediating the capillary hyperpermeability characterizing this
      syndrome.

PMID- 8752614
TI  - Vascular endothelial growth factor expression in cycling human endometrium.
AB  - OBJECTIVE: To determine the spatial distribution of vascular endothelial growth
      factor protein in human endometrium and to assess temporal fluctuations in
      vascular endothelial growth factor gene expression and variant isoform production
      by stromal and epithelial cells during the menstrual cycle. DESIGN: Prospective
      study design. PATIENTS: Early proliferative endometrial biopsies were obtained
      from women undergoing gynecologic surgery for benign conditions; secretory stage
      biopsies were obtained from patients undergoing routine infertility
      investigations without evidence of luteal insufficiency. MAIN OUTCOME MEASURE:
      Immunohistochemical detection of vascular endothelial growth factor protein in
      endometrial biopsies, analyses of vascular endothelial growth factor RNA
      expression, and isoform production in intact endometrium and isolated endometrial
      stromal and epithelial cells. RESULTS: Strong vascular endothelial growth factor
      immunoreactivity was detected in the glandular epithelial cells of the secretory
      endometrium with no discernible immunoreactivity in stroma cells. The
      proliferative endometrium demonstrated prominent glandular immunoreactivity and
      faint, inconsistent stromal cell immunoreactivity. Preincubation of the antibody
      with excess cognate peptide abolished all immunoreactivity. A threefold to
      sixfold increase in vascular endothelial growth factor messenger RNA expression
      occurs in secretory versus proliferative endometrial samples. Endometrial stromal
      and epithelial cell isolates from both phases of the menstrual cycle express
      VEGF121, VEGF165, and VEGF189 isoforms, however, vascular endothelial growth
      factor variant 206 was not detected. CONCLUSIONS: Expression of vascular
      endothelial growth factor in the endometrium throughout the menstrual cycle
      suggests that vascular endothelial growth factor may promote the vascular growth,
      maintenance, and hyperpermeability required for adequate receptivity in the
      cycling human endometrium.

PMID- 8752615
TI  - Immunohistochemical characterization of stromal leukocytes in ovarian
      endometriosis: comparison of eutopic and ectopic endometrium with normal
      endometrium.
AB  - OBJECTIVE: To compare stromal leukocyte subpopulations in different phases of the
      menstrual cycle in eutopic and ectopic endometrium from women with ovarian
      endometriosis and in control endometrium. DESIGN: Retrospective
      immunohistochemical study. SETTING: Department of Pathology, Royal Victoria
      Infirmary, Newcastle-upon-Tyne, United Kingdom. PATIENTS: Paraffin-embedded
      tissue blocks from 30 patients with endometriosis and 30 control blocks from
      patients undergoing hysterectomy for nonendometrial pathology were retrieved from
      archive files. MAIN OUTCOME MEASURE: Quantitative assessment of defined stromal
      leukocyte subpopulations in eutopic, ectopic and control endometrium at different
      stages of the menstrual cycle. RESULTS: In the proliferative and early secretory
      phases, ectopic endometrium contained elevated numbers of CD45+, CD3+, and CD43+
      cells but reduced percentages of CD68+ macrophages. The proportions of granulated
      cells were reduced in ectopic endometrium throughout the cycle. No differences
      were noted between eutopic endometrium from women with endometriosis and control
      endometrium. CONCLUSION: Differences between eutopic and ectopic leukocyte
      subpopulations with the exception of large granular lymphocytes may be due to the
      lack of cyclicity demonstrated by endometriotic lesions.

PMID- 8752616
TI  - Inhibition of oxidative modification of proteins by RU486.
AB  - OBJECTIVES: To elucidate further the antioxidant properties of RU486. We
      determined whether it can protect biologic molecules such as proteins (albumin,
      low-density lipoprotein [LDL] and oxidized LDL) from damage by pre-existing lipid
      peroxides. DESIGN: In vitro study. INTERVENTIONS: We tested the effects of RU486
      on the formation of fluorescent oxidatively modified proteins by pre-existing
      lipid peroxides. We used two model systems, the incubation of oxidized linoleic
      acid with serum albumin and the incubation of human LDL with copper. MAIN OUTCOME
      MEASURES: The formation of modified protein was established by determining
      fluorescence at excitation wavelength of 330 nm and emission wavelength between
      390 and 500 nm. Modified protein has a characteristic emission between 425 and
      430 nm. RESULTS: The addition of increasing amounts of RU486 inhibited the
      formation of fluorescent oxidatively modified protein products in both model
      systems. CONCLUSION: These results provide evidence that RU486 not only can
      prevent the formation of lipid peroxide, but also can block the formation of
      fluorescent protein adducts in the presence of pre-existing lipid peroxides.

PMID- 8752617
TI  - Seeking medical help for subfecundity: a study based upon surveys in five
      European countries.
AB  - OBJECTIVE: To study care-seeking behavior for infertility treatment in different
      European countries. DESIGN: Multicenter surveys of randomly selected women in the
      child bearing age. SETTING: Five countries participated in the study: Denmark,
      Germany, Italy, Poland, and Spain. Data were collected from 1991 to 1993 as part
      of a concerted action. PATIENTS: Population-based samples of women 25 to 44 years
      of age. The sample sizes ranged from 442 women in Poland to 2,729 in Italy.
      Participation rates ranged from 54% in Germany to 87% in Denmark. Data were
      collected by means of a highly structured questionnaire used at a face-to-face
      interview. MAIN OUTCOME MEASURES: Waiting time to pregnancy, time, and type of
      treatment for infertility. RESULTS: Less than half of the infertile couples seek
      medical help in most European countries. The lowest proportion seeking help was
      found in Poland and the highest in Denmark. CONCLUSION: The increasing demand for
      infertility treatment is expected to continue, because the potential unmet need
      is outspoken in most European countries.

PMID- 8752618
TI  - Laboratory criteria for menopause in women using oral contraceptives.
AB  - OBJECTIVE: To evaluate laboratory criteria for menopause in women talking oral
      contraceptives (OC). DESIGN: Prospective, uncontrolled pilot study. SETTING: San
      Francisco General Hospital, San Francisco, California, and Magee-Womens Hospital,
      Pittsburgh, Pennsylvania. PATIENTS: Twenty-eight menopausal women. INTERVENTIONS:
      Fourteen menopausal women received triphasic 35 micrograms ethinyl E2 and 180-215
      250 micrograms norgestimate, and 14 menopausal women received monophasic 30
      micrograms ethinyl E2-150 micrograms desogestrel. MAIN OUTCOME MEASURES: Serum
      FSH, LH, and E2 levels were evaluated on days 14 and 28 (day 7 of the pill-free
      interval) of the third cycle of pills. RESULTS: Twelve women in each group
      completed the study. Fifteen (62.5%) subjects still had a serum FSH < 30 mIU/mL
      (30 IU/L) on the 7th day of the pill-free interval of the third pill package. All
      subjects had a serum FSH:LH ratio > 1 and 20 of 21 (95%) subjects had E2 < 20
      pg/mL (73 pmol/L) at the end of the pill-free interval of the third cycle.
      CONCLUSIONS: Measuring FSH on the 7th day of the pill-free interval is not a
      sensitive test for menopause. Serum FSH:LH ratio > 1 or E2 < 20 pg/mL (73 pmol/L)
      on the 7th day of the pill-free interval may be a more appropriate marker of
      menopause in women using OC in the later reproductive years.

PMID- 8752619
TI  - Perinatal outcome of twin pregnancies obtained after in vitro fertilization:
      comparison with twin pregnancies obtained spontaneously or after ovarian
      stimulation.
AB  - OBJECTIVE: To compare the perinatal outcome of IVF-ET twin pregnancies to twin
      pregnancies conceived spontaneously or after ovarian stimulation without IVF-ET.
      DESIGN: Retrospective analysis. PATIENTS: Three groups of patients: those who
      conceived after IVF-ET (n = 72), after ovarian stimulation without IVF-ET
      (stimulation group, n = 82), or spontaneously (spontaneous group, n = 164). MAIN
      OUTCOME MEASURES: High blood pressure, premature rupture of membrane, threatened
      premature labor, prematurity, low birth, small-for-gestational-age, cesarean
      section, and perinatal mortality. RESULTS: Patients of the IVF-ET group were
      older and of higher socioeconomic class. We did not find any significant
      difference in the data analyzed, with the exception of the rate of emergency
      cesarean sections. In the IVF-ET group the prematurity rate (38.9%), small-for
      gestational-age (18%), and perinatal mortality (3.47%) were not statistically
      different with respect to the stimulation group (45.1%, 23.2%, and 3.05%,
      respectively) or the spontaneous group (39.6%, 22.7%, and 4.27%, respectively).
      CONCLUSIONS: Twin pregnancies account for 20% to 25% of all IVF-ET pregnancies.
      Their risk of adverse perinatal outcome does not seem to be increased when
      compared with spontaneous pregnancies or to pregnancies obtained after ovarian
      stimulation but without IVF-ET. However, a reduction in the proportion of
      multiple pregnancies, including twin gestation, should be a goal for IVF-ET
      teams.

PMID- 8752621
TI  - Reinsemination of one-day-old oocytes by use of intracytoplasmic sperm injection.
AB  - OBJECTIVE: To evaluate the possible advantages of reinseminating oocytes by use
      of intracytoplasmic sperm injection (ICSI). DESIGN: Clinical study. SETTING: In
      vitro fertilization unit with research facilities. PATIENTS: Fifty-seven couples
      who were part of our regular IVF program. INTERVENTIONS: Nonfertilized oocytes
      from IVF cycles with no or very low fertilization were microinjected with
      spermatozoa approximately 25 hours after oocyte pick-up. MAIN OUTCOME MEASURES:
      Fertilization and pregnancy rates. RESULTS: A mean fertilization rate of 46.5%
      was obtained when reinseminating the oocytes on day 2 using the ICSI procedure.
      Of 57 cycles with completely or almost completely failed fertilization, 29
      patients received ET after reinsemination by ICSI. Two of these transfers
      resulted in pregnancies (6.9% per ET) and two healthy babies were born.
      CONCLUSION: Despite this relative success, considering both the extra work
      involved and the potential genetic risk, it is doubtful whether ICSI on day 2
      should be recommended as a routine procedure. For training and research purposes,
      however, this approach can be of value.

PMID- 8752622
TI  - Deleterious effect of the presence of hydrosalpinx on implantation and pregnancy
      rates with in vitro fertilization.
AB  - OBJECTIVE: To determine the effect of the presence of a unilateral or bilateral
      hydrosalpinx on the outcome with IVF-ET. DESIGN: Retrospective analysis of
      clinical and laboratory data. SETTING: Hospital-based private IVF center.
      PATIENTS: Eight hundred forty-six patients with tubal disease younger than age 40
      years undergoing 1,766 stimulation cycles. In 118 cycles, a hydrosalpinx was
      noted sonographically (group I) whereas, in 1,648 cycles, no such image was
      documented. MAIN OUTCOME MEASURES: Pregnancy and implantation rates. RESULTS:
      Group I displayed a significantly lower pregnancy rate per transfer than group II
      (16.84% versus 36.83%) and a lower implantation rate (3.92% versus 11.53%).
      CONCLUSION: The presence of hydrosalpinx adversely affects the outcome of IVF.

PMID- 8752620
TI  - Normal pregnancies resulting from testicular sperm extraction and
      intracytoplasmic sperm injection for azoospermia due to maturation arrest.
AB  - OBJECTIVE: To see whether testicular sperm extraction could be used to perform
      intracytoplasmic sperm injection (ICSI) for men with nonobstructive azoospermia
      caused by maturation arrest. DESIGN: Uncontrolled prospective trial of an attempt
      to find occasional elongated spermatids or spermatozoa in testes of azoospermic
      patients with maturation arrest and to use these haploid cells for ICSI. SETTING:
      European university-based center for reproductive medicine and private American
      community hospital. PATIENTS: Thirty-eight azoospermic males without obstruction
      and with biopsy-documented maturation arrest, seven of whom elected, with their
      wives, to undergo scrotal exploration and testicular sperm extraction with ICSI
      in an attempt to become pregnant. INTERVENTIONS: Histologic evaluation of
      spermatid development in 38 patients with azoospermic maturation arrest.
      Testicular sperm extraction with ICSI in seven random volunteers from this group.
      MAIN OUTCOME MEASURES: Presence or absence of mature spermatids in the testis
      biopsy specimen of patients with azoospermic maturation arrest. Fertilization,
      cleavage, and pregnancy after testicular sperm extraction and ICSI in patients
      with azoospermic maturation arrest. RESULTS: All seven patients with azoospermic
      maturation arrest had occasional sperm found with testicular sperm extraction.
      Five had sufficient numbers (between 6 and 30) for ICSI, and those five had ETs.
      In four, the partners became pregnant. In all 38 patients examined, the
      maturation defect was in meiosis rather than in spermiogenesis. CONCLUSION:
      Nonobstructive azoospermia caused by maturation arrest may be treated with
      testicular sperm extraction with ICSI apparently as successfully as Sertoli cell
      only.

PMID- 8752623
TI  - Birth of healthy children after preimplantation diagnosis of common aneuploidies
      by polar body fluorescent in situ hybridization analysis. Preimplantation
      Genetics Group.
AB  - OBJECTIVE: To perform preimplantation diagnosis of common aneuploidies by polar
      body analysis and fluorescent in situ hybridization technique using probes
      specific for chromosomes X, 18, and 13/21. DESIGN: The first and/or second polar
      bodies were removed and studied by fluorescent in situ hybridization to detect
      and avoid fertilization and transfer of oocytes with common aneuploidies.
      SETTING: The Reproductive Genetics Institute's IVF program at Illinois Masonic
      Medical Center. PATIENTS: One hundred ninety-three couples of advanced maternal
      age (34 to 46 years) under-going IVF treatment volunteered to be part of a
      clinical trial on preimplantation polar body diagnosis of common aneuploidies.
      INTERVENTIONS: Using micromanipulation procedures, the first and second polar
      bodies were removed after their extrusion from the oocytes. MAIN OUTCOME MEASURE:
      Fluorescent in situ hybridization signals specific for chromosomes X, 18, and
      13/21. RESULTS: In 235 IVF cycles performed in 193 couples, 1,293 oocytes were
      biopsied and subjected to fluorescent in situ hybridization analysis, with
      fluorescent in situ hybridization results available in 993 oocytes (76.8%). Of
      993 oocytes with fluorescent in situ hybridization results, 665 (67%) were
      predicted to be normal based on the chromosomes studied; 460 embryos resulting
      from these oocytes were transferred in 187 treatment cycles, resulting in 12
      births of healthy children and 18 ongoing pregnancies after confirmation of the
      polar body diagnosis by chorionic villus sampling or amniocentesis. CONCLUSION:
      Polar body fluorescent in situ hybridization analysis may be used for
      preimplantation diagnosis of common aneuploidies in IVF patients of advanced
      maternal age.

PMID- 8752624
TI  - Transvaginal Doppler study of uterine artery blood flow in in vitro fertilization
      embryo transfer cycles.
AB  - OBJECTIVE: To verify whether uterine artery impedance, measured as pulsatility
      index and resistance index is related to the outcome of in IVF-ET cycles. DESIGN:
      Prospective study of infertile women participating in an IVF-ET program. SETTING:
      University Hospital. PATIENTS: Two hundred women (24 to 40 years of age), who had
      one to three good quality embryos transferred to the uterus after a standardized
      IVF cycle. INTERVENTION: Transvaginal color Doppler and a blood sample on the day
      of ET. MAIN OUTCOME MEASURES: Uterine artery pulsatility index and resistance
      index, endometrial thickness, serum E2 and P concentrations, clinical pregnancy
      rate (PR). RESULTS: Pulsatility indices and resistance indices were lower in
      conception (2.45 +/- 0.54 and 0.85 +/- 0.04, respectively) than in nonconception
      cycles (2.66 +/- 0.39 and 0.87 +/- 0.04, respectively), although the overlap of
      the values is considerable. Overall PR was 35% per ET, and it decreased
      significantly when pulsatility index was > 3.0 (15%) and resistance index > 0.92
      (13%), being lowest when pulsatility index was > 3.3 and resistance index > 0.95
      (10%). Such a high impedance was detected in 9% of nonconception cycles.
      CONCLUSION: In IVF-ET cycles the uterus is likely to be unreceptive when uterine
      artery pulsatility index is > 3.3 and resistance index > 0.95 before ET, but this
      occurs only in 9% of the cycles.

PMID- 8752625
TI  - Distinct expression levels of cytokines and soluble cytokine receptors in seminal
      plasma of fertile and infertile men.
AB  - OBJECTIVE: To compare the levels of interleukin (IL) 1 beta, IL-6, tumor necrosis
      factor (TNF) alpha, and soluble TNF (sTNF) receptors types I and II, and IL-1
      receptor antagonist in seminal plasma of fertile and infertile men. DESIGN:
      Prospective and comparative study. SETTING: Andrology clinic of a university
      hospital. PATIENTS: Four groups of normogonadotropic men: group 1, donors with
      proven fertility (controls, n = 15); group 2, azoospermic men (n = 12); group 3,
      infertile men with oligoteratoasthenospermia (n = 20); and 11 men with
      oligoteratoasthenospermia and genital infection (n = 11). INTERVENTIONS: None.
      MAIN OUTCOME MEASURE: Measurement of cytokines and cytokine-soluble receptors in
      the semen by specific commercial kits. RESULTS: The levels of IL-1 beta, TNF
      alpha, and IL-6 were similar in seminal plasma of controls and infertile men. The
      mean level of sTNF-I receptor in the seminal plasma of group 4 was 2.4 +/- 0.2
      ng/mL, which was significantly lower than observed in seminal plasma of group 1
      (3.88 +/- 0.5 ng/mL), the group 3 (4.1 +/- 0.4 ng/mL), or group 2 (3.03 +/- 0.35
      ng/mL). The soluble receptor of TNF-II could not be detected in any group.
      Interleukin 1ra was 120 +/- 10 pg/mL in seminal plasma of group 1, but increased
      levels were detected in group 2 (420 +/- 180 pg/mL), group 3 (480 +/- 90 pg/mL),
      and even higher (760 +/- 120 ng/mL) in group 4 patients. CONCLUSIONS: During
      genital infection cytokines and various soluble receptors of immunoregulatory
      cytokines are expressed distinctly in seminal plasma. These factors also may be
      involved in the regulation of sperm cell functions and thus may affect male
      fertility. Our results may indicate local production of these factors in the
      secondary sex glands, independently of spermatogenesis.

PMID- 8752626
TI  - Role of hypoestrogenism or sex steroid antagonism in adhesion formation after
      myometrial surgery in primates.
AB  - OBJECTIVE: To determine the contribution of estrogen in the development of pelvic
      adhesions during myometrial surgery. DESIGN: A randomized, prospective study in
      the nonhuman primate. SETTING: A primate colony, Department of Obstetrics and
      Gynecology, Eastern Virginia Medical School. INTERVENTIONS: All primates were
      assigned prospectively to one of three treatment groups: [1] GnRH analogue (GnRH
      a), [2] mifepristone, or [3] vehicle control. After 3 months of treatment, a
      standard uterine fundal hysterotomy, for full thickness endometrial biopsy, was
      performed at the time of exploratory laparotomy, with subsequent scoring of utero
      omental adhesions to the hysterotomy site at a future staging procedure based
      upon adhesion area, vascularity, and tenacity. Serum was drawn on the day of
      surgery for E2 determination. Endometrial height, from the surface interface
      between the endometrium and myometrium, was used as a bioassay of estrogen
      activity. RESULTS: The hypoestrogenic (GnRH-a) group and the mifepristone group
      had significantly fewer utero-omental adhesions compared with the normally
      cycling control monkeys as measured by a lower adhesion score. Similarly, the
      endometrial thickness was significantly reduced in the GnRH-a and mifepristone
      groups (one-third) compared with the cycling controls, demonstrating the effects
      of either hypoestrogenism or noncompetitive estrogen antagonism. Serum E2 on the
      day of surgery was predictive of the postoperative adhesion score by both a
      regression analysis and analysis of covariance. CONCLUSIONS: The actions of E2
      seem to have a dramatic effect on the formation of pelvic adhesions after
      myometrial surgery.

PMID- 8752627
TI  - Use of recombinant human follicle-stimulating hormone for in vitro fertilization
      embryo transfer after severe systemic immunoglobulin E-mediated reaction to
      urofollitropin.
AB  - OBJECTIVE: To report the successful use of recombinant human FSH in a patient
      with a history of a severe systemic immunoglobulin E (IgE)-mediated reaction to
      urofollitropin. SETTING: University hospital. PATIENT: A 38-year-old infertility
      patient who had experienced a whole-body rash with hives, tachycardia, fever, and
      other symptoms after urofollitropin administration, with confirmation of IgE
      mediated sensitivity to urofollitropin by intradermal skin testing. INTERVENTION:
      In vitro fertilization-ET after the use of recombinant human FSH to stimulate
      ovarian follicular development. RESULTS: Establishment of a clinical pregnancy.
      CONCLUSIONS: Our case provides evidence for the involvement of nongonadotropin
      proteins as the direct cause of some adverse reactions from conventional urine
      derived human FSH preparations.

PMID- 8752628
TI  - Triggering of ovulation by a gonadotropin-releasing hormone (GnRH) agonist in
      patients pretreated with a GnRH antagonist.
AB  - OBJECTIVE: To determine if GnRH-agonist (GnRH-a) could induce a LH surge in
      patients where a GnRH antagonist was used to prevent premature spontaneous LH
      surge. DESIGN: Pilot study. PATIENTS: Five patients treated with ovarian
      stimulation and IUI for idiopathic infertility. MAIN OUTCOME MEASURES:
      Luteinizing hormone, FSH, and P plasma levels. RESULTS: A LH and FSH surge as
      well as a P rise were obtained in the five patients studied. CONCLUSION: A GnRH-a
      successfully can induce an LH surge after GnRH antagonist administration. The
      effect of the antagonist on the quality of the GnRH-a-induced LH surge as well as
      the oocyte quality remain to be evaluated.

PMID- 8752629
TI  - Glucocorticoid administration during transfer of frozen-thawed embryos: a
      prospective, randomized study.
AB  - OBJECTIVE: To establish whether there is any improvement in pregnancy and
      implantation rates after administration of "low-dose," long-acting
      glucocorticoids during transfer of cryopreserved-thawed embryos. SETTING: An IVF
      unit in a university hospital. DESIGN: Prospective, randomized study. Ninety-nine
      consecutive transfer cycles of frozen-thawed embryos to the uterine cavity of
      randomly chosen women diagnosed as having tubal factor infertility only. Fifty
      two patients underwent transfer of frozen-thawed embryos and received 0.5 mg of
      dexamethasone; 47 women (control group) did not receive the drug during transfer.
      PATIENTS: Normal ovulatory patients with tubal factor infertility. INTERVENTIONS:
      Oral dexamethasone administration before, during and after transfer of thawed
      embryos. MAIN OUTCOME MEASURES: Pregnancy and implantation rates. RESULTS: The
      pregnancy rate was 13.5% (7/52) in patients treated with the "low-dose" regimen
      of dexamethasone compared with 12.8% (6/47) in the control group. The
      implantation rate was similar. CONCLUSION: Our results demonstrated that the use
      of 0.5 mg dexamethasone for an immuno-suppressive effect, administered for a
      short period to patients diagnosed as having "pure" tubal factor infertility, did
      not improve the implantation or pregnancy rates.

PMID- 8752630
TI  - Fertilization and embryo cleavage after intracytoplasmic spermatid injection in
      an obstructive azoospermic patient with defective spermiogenesis.
AB  - OBJECTIVE: To achieve fertilization and cleavage by spermatids without tails from
      testicular biopsy. DESIGN: Clinical trial. SETTING: Reproductive unit of a
      university teaching hospital. PATIENT: A patient of obstructive azoospermia with
      defective spermiogenesis. INTERVENTION: Testicular biopsy after scrotal
      exploration and spermatid injection into the cytoplasm of oocyte. MAIN OUTCOME
      MEASURES: Fertilization and cleavage. RESULTS: Four of 13 spermatid injections
      achieved normal fertilization and 2 of them cleaved. CONCLUSION: Intracytoplasmic
      spermatid injection may be a possible treatment for patients of defective
      spermiogenesis who have no viable spermatozoa available.

PMID- 8752631
TI  - Risks for transmission of hepatitis C virus during artificial insemination.
AB  - OBJECTIVE: To identify risks of hepatitis C virus transmission by semen from
      infected donors. DESIGN: Case report. SETTING: Assisted fertility clinic.
      PATIENTS: Hepatitis C virus-infected semen donor and recipients of his donations.
      INTERVENTION: Testing for hepatitis C virus by serology and polymerase chain
      reaction. MAIN OUTCOME MEASURES: Detection of hepatitis C virus antibodies and
      viral RNA. RESULTS: Hepatitis C virus RNA was detected in the semen donation
      before but not after purification; none of the recipients of the donors samples
      were found to have antibodies to hepatitis C virus. CONCLUSIONS: Hepatitis C
      virus RNA can be detected in semen donations from infected donors; purification
      of donations before insemination significantly reduces the amount of viral RNA in
      the semen pellet.

PMID- 8752632
TI  - Efficacy of recombinant follicle-stimulating hormone.

PMID- 8752633
TI  - In vitro fertilization patient population on which to base predictive testing?

PMID- 8752634
TI  - Transgenic sperm or deadly missiles?

PMID- 8752635
TI  - The efficacy of "tubal sperm perfusion"?

PMID- 8752636
TI  - Multiple gestation after "high-order" oocyte transfer.

PMID- 8752637
TI  - Time to pregnancy-after ectopic.

PMID- 8752638
TI  - Albumin for ovarian hyperstimulation?

PMID- 8752639
TI  - Differential age of the endometrium.

PMID- 8752640
TI  - Laparoscopic-assisted resection of colon.

PMID- 8752641
TI  - The future of dental education.

PMID- 8752642
TI  - [Denturology].

PMID- 8752643
TI  - Infection control procedures--who should decide what cannot be used?

PMID- 8752644
TI  - The law and ethics regarding infection control in treating HIV-positive patients.

PMID- 8752645
TI  - Continuing investigation and controversy regarding risk of transmission of
      infection via dental handpieces.
AB  - Current epidemiologic evidence indicates that infectious diseases, specifically
      blood-borne pathogens such as hepatitis B, hepatitis C and HIV, are not
      transmitted from patient to patient via dental instruments. However, ongoing
      laboratory investigations suggest that potential pathogens may be retained within
      dental handpieces, creating a theoretical risk of cross infection. Controversy
      regarding certain laboratory study results and the clinical implications of these
      studies continues. Guidelines and regulations for infection control should be
      rational, and based on a realistic response to a documented risk. Dental
      professionals should be aware of continuing research focusing on these issues.

PMID- 8752647
TI  - Danger of inter-patient cross-contamination from saliva ejector suck back.

PMID- 8752646
TI  - Dental unit water contamination.
AB  - Bacteria-laden biofilms located on the lumen surface of dental unit water lines
      have resulted in the persistent and widespread microbial contamination of dental
      unit water supplies. These biofilms are resistant to chemical disinfection. As
      such, they act as reservoirs that facilitate the continuous re-contamination of
      dental unit water. The microbial populations of the biofilms found in dental unit
      water lines include opportunistic pathogens of unknown significance. Strategies
      to control the contamination are discussed.

PMID- 8752648
TI  - Successive cusp build-up: an improved placement technique for posterior direct
      resin restorations.

PMID- 8752649
TI  - Dental office ergonomics: how to reduce stress factors and increase efficiency.
AB  - Ergonomics, the science that studies human stress and strain related to
      activities, has one primary objective-to prevent work related musculoskeletal
      disorders, or symptoms that aggravate these disorders. Smart business owners have
      adopted the practice of ergonomics as an integral element in their ongoing
      strategies to increase productivity and ensure reduced workers' compensation
      liability. In British Columbia, however, potentially expensive ergonomic draft
      regulations created by the province's Workers' Compensation Board in 1993, have
      been put on hold. These ergonomic standards-described as the stiffest in the
      world -were to have been implemented across the province in early 1995.
      Nonetheless, ergonomic practices are alive and thriving in Canadian businesses
      that are devoted to ensuring a reduction in work-related injuries and salvaging
      potentially lost productivity. Although it is difficult to document lost
      productivity, Ontario's Workers' Compensation Board reported that it received 707
      repetitive stress injury claims from office workers in 1992, with a per person
      cost of $7,703. In addition to these costs, each claimant took about 93 days off
      work. In dentistry, poor working habits, along with repetitive tasks, such as
      scaling and root planing, contribute greatly to musculoskeletal disorders, stress
      claims and lost productivity. Our tendency is to adapt awkward and illogical
      physical postures to access the oral cavity. The key objective for clinicians is
      to find a position that allows them to achieve optimum access, visibility,
      comfort and control at all times. With the professional goal to deliver the
      highest quality of care for a reasonable profit, the practice of ergonomics
      becomes a core focus in determining how to achieve practice success with less
      stress.

PMID- 8752650
TI  - Time is on our side.

PMID- 8752651
TI  - Adenoviral-mediated herpes simplex virus-thymidine kinase gene transfer in vivo
      for treatment of experimental human melanoma.
AB  - To assess the efficacy of an in vivo adenoviral-mediated cytotoxic gene therapy,
      human melanomas were established in nude mice and transduced with herpes simplex
      virus-thymidine kinase (tk) followed by treatment with ganciclovir (GCV). In
      initial experiments, adenovirus (adv) containing the beta-galactosidase reporter
      gene was employed to determine melanoma cell infectivity in vitro. In comparison
      to murine melanoma cell lines B16 and K1735-M2, human A375-SM cells exhibited up
      to a 10-fold greater susceptibility to adenoviral transduction, similar to the
      degree of infectivity found for human epidermal HaCaT cells. In addition, human
      A375-SM melanoma cells exhibited a greater sensitivity in vitro to the cytotoxic
      effects of transduction with tk-adv and treatment with GCV, which was mediated by
      a strong bystander effect. In vivo, intratumoral injection of relatively large
      human melanomas (160 mm3) with 1.2 X 109 pfu of tk-adv, followed by
      intraperitoneal GCV treatment (60 mg/kg twice daily) over 4 days, typically
      resulted in a 50% reduction in melanoma growth rate compared to mock or untreated
      controls. Moreover, histometrical analysis employing a rigorous computerized
      imaging system revealed that the residual viable tumor area in the tk-adv/GCV
      treated group was only one-fifth that of solvent controls. These data show that
      adv is a highly efficient in vivo gene delivery system to treat experimental
      human melanomas. In comparison to a previous murine melanoma study, human
      melanomas appeared to exhibit a greater sensitivity to this cytotoxic treatment
      in vivo, which may hold significant promise for development of effective gene
      therapy modalities to treat melanoma in humans.

PMID- 8752652
TI  - Increased epidermal growth factor receptor in fsn/fsn mice.
AB  - Epidermal growth factor receptors (EGF-Rs) are elevated in active human psoriatic
      lesions, but decrease in resolving lesions. Similar biologic responses in EGF-R
      levels have been demonstrated within human psoriatic skin grafted onto mice. We
      tested the hypothesis that flaky-skin mice (fsn/fsn), one proposed genetic animal
      model of psoriasis, would display EGF-R levels comparable to human psoriatic
      epidermis and show similar biologic responses. EGF-R levels were characterized in
      unperturbed sites in fsn/fsn skin and +/? skin by enzyme-linked immunosorbent
      assay, 125I-EGF binding, and immunostaining. Altered EGF-R levels were noted
      after mild trauma (tape stripping) or under resolving conditions (30 doses of 50
      mJ/CM2 ultraviolet B, 2.5 mg/kg oral cyclosporin A, or daily 30 microg/ml topical
      EGF). Increased EGF-R immunostaining was observed in involved flaky epidermal
      sites before treatment. To determine whether a hyperproliferative (Koebner)
      reaction could be induced, we tape stripped fsn/fsn tail and non-flaky dorsal
      sites. EGF-R levels in dorsal epidermis increased by days 3-4 after injury by
      enzyme-linked immunoabsorbent assay methods. When fsn/fsn mice received one of
      three different treatments for 6 weeks, the skin returned to a normal phenotype
      both grossly and microscopically. Immunoreactive EGF-R in treated, but not
      untreated, sites decreased to either normal or nondetectable levels. These data
      indicate that fsn/fsn mice exhibit an EGF-R profile identical to that of lesional
      and nonlesional human psoriatic epidermis. Modulations of the flaky phenotype in
      response to injury and three different treatments suggest that fsn/fsn is a
      useful in vivo model for examining new treatment modalities for psoriasiform skin
      diseases.

PMID- 8752653
TI  - Expression of the human alpha2 integrin subunit in mouse melanoma cells confers
      the ability to undergo collagen-directed adhesion, migration and matrix
      reorganization.
AB  - Previous studies have shown that cultured human and other mammalian cell require
      the alpha2 beta1 integrin receptor to reorganize and contract 3-dimensional
      extracellular matrix lattices containing collagen type I. This function is of
      prime importance for the later phases of wound healing, in which fibroblasts
      reorganize and contract extracellular matrix components newly deposited in the
      granulation tissue. It is also known that highly aggressive human melanoma cells
      have acquired this function, possibly enhancing their invasive potential. To
      further study alpha2 beta1-mediated functions, we expressed the human alpha2 and
      beta1 chains of integrins in mouse melanoma cells (BULT). The parental cell line
      was unable to exert known alpha2 beta1-mediated functions: The cells did not
      adhere, spread, or migrate on collagen type I, and they did not reorganize 3
      dimensional collagen I lattices. Transfection of the human alpha2 chain was
      sufficient to confer not only specific adhesion to collagen type I in static
      adhesion assays, but also the ability to exert complex functions such as
      migration on collagen and efficient reorganization of collagen-I-containing
      matrices. Coexpression of the human beta1 chain did not further enhance these
      functions in BULT melanoma cells. This was underscored by the observation that
      alpha1-specific monoclonal antibodies were able to completely block the newly
      introduced functions, whereas beta1-specific antibodies had no such effect.
      Moreover, in transfectants expressing both the human alpha2 and beta1 chains, the
      human alpha2 chain did not preferentially associate with the human beta1 chain as
      compared with mouse beta-chains. This may indicate that the molecular structures
      guiding the physical association of the human alpha2 chain with beta chains are
      extremely highly conserved between the species.

PMID- 8752654
TI  - CD23-mediated nitric oxide synthase pathway induction in human keratinocytes is
      inhibited by retinoic acid derivatives.
AB  - Retinoids exert various functions including anti-proliferative and anti
      inflammatory effects on many cell types including keratinocytes and are widely
      used in skin diseases, such as psoriasis and acne. We have previously shown that
      human keratinocytes express low affinity immunoglobulin E receptor
      (FcepsilonRII/CD23) when stimulated with interleukin-4. Immunoglobulin E ligates
      CD23 and induces the production of nitrites (reflecting the mobilization of the
      nitric oxide [NO]-pathway) and tumor necrosis factor-alpha by human
      keratinocytes. Here, 13-cis and all-trans retinoic acid (RA) were shown to reduce
      the production of nitrites by immunoglobulin E-activated keratinocytes by 80% in
      a time- and concentration-dependent fashion. As a consequence, RA derivatives
      also reduced the production of tumor necrosis factor alpha by these cells by 70%.
      The level of inducible NO synthase activity in activated human keratinocytes was
      significantly decreased upon treatment of the cells with RA derivatives
      (inhibition by 60% of the mean inducible NO synthase activity with 13-cis RA, 2
      microM). Treatment for 24 h with RA derivatives almost completely abolished
      transcription of inducible NO synthase-specific mRNA in activated keratinocytes.
      Therefore, RA derivatives downregulate tumor necrosis factor-alpha release and
      the NO-transduction pathway through the inhibition of inducible NO synthase
      transcription. Together, our data provide evidence for inhibition of the NO
      pathway by 13-cis and all-trans retinoic acid on CD23-activated human
      keratinocytes. These data may clarify the mechanism of the anti-inflammatory
      activity of RA derivatives in skin diseases.

PMID- 8752655
TI  - Interleukin-12 prevents ultraviolet B-induced local immunosuppression and
      overcomes UVB-induced tolerance.
AB  - Ultraviolet (UV) light abrogates contact hypersensitivity (CHS) responses and
      induces hapten-specific tolerance. Because Th-1 cells are critically involved in
      CHS and are induced to develop by the cytokine interleukin (IL)-12, we asked
      whether IL-12 might overcome UV-induced local immunosuppression. C3H/HeN mice
      exposed to low doses of UV light over 4 d and hapten sensitized through the
      irradiated skin area with dinitrofluorobenzene showed profound inhibition of the
      CHS response, which was completely prevented upon intraperitoneal injection of
      murine recombinant IL-12 (rIL-12) after the last UV exposure. UV-treated mice
      resensitized 14 d after the first challenge displayed hapten-specific tolerance,
      whereas UV-exposed mice injected with rIL-12 before the first sensitization
      exhibited a vigorous CHS response. Furthermore, mice that were initially
      sensitized through UV-exposed skin also produced a significant CHS reaction when
      they received rIL-12 before resensitization. Adoptive transfer of spleen and
      lymph node cells from UV-irradiated mice treated with rIL-12 had no effect on the
      CHS response in recipient mice, whereas transfer of cells from UV-treated mice
      inhibited the immune response. These findings demonstrate that rIL-12 can prevent
      UV-induced local immunosuppression and overcome UV-induced hapten-specific
      tolerance.

PMID- 8752656
TI  - Transforming growth factor-alpha induces interleukin-6 in the human keratinocyte
      cell line HaCaT mainly by transcriptional activation.
AB  - There is ample evidence that several cytokines, including transforming growth
      factor-alpha (TGF-alpha), interleukin (IL)-6, and IL-8 are upregulated in
      psoriasis, suggesting a pathogenic role for these cytokines. The sequence of
      these events, however, has not been elucidated. Recently it has been reported
      that TGF-alpha induces IL-6 in thymocytes through posttranscriptional regulation;
      therefore, we were interested in whether TGF-alpha can also induce IL-6 in human
      keratinocytes. Thus, we stimulated the human keratinocyte cell line HaCaT with
      TGF-alpha and tested supernatants for IL-6 activity. TGF-alpha resulted in a
      significant induction of the release of IL-6. This was also confirmed by northern
      blot analysis, which revealed a transient increase in IL-6 mRNA. This increase
      was unlikely due to enhanced mRNA stability, because we could not observe
      induction of IL-6 -specific transcripts by TGF-alpha in the presence of
      actinomycin D. To determine whether IL-6 induction by TGF-alpha is
      transcriptionally regulated, we transfected fragments of the IL-6 upstream
      region, subcloned into a plasmid just upstream of the chloramphenicol acetyl
      transferase coding region, into HaCaT cells. A 238-bp fragment and a 123-bp
      fragment, both containing nuclear factor (NF)-IL-6 and NFkappaB sites, exhibited
      significant induction of chloramphenicol acetyl transferase activity upon
      treatment with TGF-alpha. Because IL-6 transcription is known to be regulated by
      activation of NFkappaB and NF-IL-6, we analyzed the activation of these DNA
      binding proteins by electrophoretic mobility shift assays. NF-IL-6 binding to a
      32P-labeled NF-IL-6 binding sequence was enhanced 20 min after TGF-alpha
      stimulation and returned to basal levels within 90 min, whereas NFkappaB binding
      activity was enhanced after 20 min and returned to normal 60 min after
      stimulation. We conclude that TGF-alpha induces IL-6 in HaCaT cells and, in
      contrast to thymocytes, may do so by transcriptional activation, possibly through
      activation of NFkappaB and NF-IL-6.

PMID- 8752657
TI  - Comet assay demonstrates a higher ultraviolet B sensitivity to DNA damage in
      dysplastic nevus cells than in common melanocytic nevus cells and foreskin
      melanocytes.
AB  - We used the single cell gel electrophoresis assay (comet assay) to study
      ultraviolet B (UVB)-induced DNA damage in pigment cells. This assay detects DNA
      damage, mainly DNA strand breaks and alkali labile sites in the DNA molecule. We
      studied the effect of biologically relevant doses (comparable to 2-3 MED (minimal
      erythemal dose) for in vivo irradiated full-thickness skin) of monochromatic UVB
      light of 302 nm on cultured melanocytes derived from foreskin, common melanocytic
      nevi, and dysplastic nevi. We were able to demonstrate a linear dose-response
      relationship between UV dose and the migration coefficient of the comet tail in
      all three types of pigment cells. Nevus cells originating from dysplastic nevi
      showed the highest sensitivity to UVB irradiation: 65% higher induction of DNA
      damage compared to the induction in foreskin melanocytes. Common melanocytic
      nevus cells were most resistant and showed a 30% lower induction of DNA damage in
      comparison to foreskin melanocytes. Differences in chromatin structure and cell
      cycle profile may influence the results of the comet assay. Control experiments
      with x-ray irradiation, which is well known to produce direct DNA strand breaks
      via radical formation, revealed only small differences between the three types of
      melanocytic cells. It is unlikely, therefore, that intrinsic nuclear
      characteristics may account for the observed differences.

PMID- 8752658
TI  - Pharmacological disruption of hair follicle pigmentation by cyclophosphamide as a
      model for studying the melanocyte response to and recovery from cytotoxic drug
      damage in situ.
AB  - Here we show that cyclophosphamide induces disruption of follicular
      melanogenesis, which is characterized by abnormal transfer of pigment granules to
      ectopic hair bulb locations, extrafollicular melanin incontinence, disordered
      formation of melanosomes, and inhibition of melanosome transfer into precortical
      keratinocytes. This is in contrast to dexamethasone-induced termination of
      follicle melanogenesis, which activates premature but predominantly normal
      catagen development. Cyclophosphamide-induced pigmentation disruption was
      accompanied by significant alterations of biochemical and biophysical markers of
      melanogenesis, compared to control mice treated either with vehicle or with
      topical dexamethasone. Electron paramagnetic resonance spectroscopy shows a
      decline in the melanin signal and predominant eumelanin production. Tyrosine
      hydroxylase activity of tyrosinase and dihydroxyphenylalanine oxidation drop
      rapidly, while DOPAchrome tautomerase activity increases and dihydroxyindole
      carboxylic acid conversion factor activity remains unchanged in cyclophosphamide
      treated mice compared to controls. These observations emphasize the key role of
      tyrosinase as opposed to postdihydroxyphenylalanine oxidase steps in normal and
      pathological termination of melanogenesis and shows that tyrosinase is the most
      sensitive target of the melanogenic apparatus for pharmacological regulation.
      Follicle pigmentation recovers only during the subsequent hair cycle, i.e., after
      a new anagen hair bulb has been constructed, which points to the existence of a
      relatively chemoresistant melanoblast-like cell population residing in the
      noncycling part of the hair follicle.

PMID- 8752659
TI  - Activation of Raf-mitogen-activated protein kinase signaling pathway by 1,25
      dihydroxyvitamin D3 in normal human keratinocytes.
AB  - The biologic effects of the vitamin D hormone 1,25-dihydroxyvitamin D3
      (1,25(OH)2D3) are believed to be mediated by an intracellular vitamin D receptor,
      which after ligand binding acts as a transcription factor modulating expression
      of a variety of genes. Besides having a well-known role in calcium metabolism,
      this hormone is an important regulator of proliferation in a majority of normal
      and neoplastic cells. Keratinocytes provide a convenient model for investigating
      the growth-related effects of vitamin D in normal cells. Growth of keratinocytes
      may be either stimulated or inhibited by 1,25(OH)2D3, depending on the degree of
      cell differentiation. We show here that 1,25(OH)2D3 stimulates DNA synthesis via
      sequential activation of Raf and the mitogen-activated protein kinase. Activation
      of these kinases is independent on protein and mRNA synthesis and is preceded by
      rapid tyrosine phosphorylation of an adaptor protein p66 (Shc) and formation of a
      complex between p66 Shc, a bridging molecule Grb2, and a Ras activator, mSos.
      Vitamin D receptor protein associates with Shc, indicating that this steroid
      hormone is able to signal through the transcription-independent pathways similar
      to those used by peptide hormones and cytokines.

PMID- 8752660
TI  - Epidermal keratinocyte production of interferon-gamma immunoreactive protein and
      mRNA is an early event in allergic contact dermatitis.
AB  - Previous work has indicated the importance of cytokine cascades in the induction
      of contact dermatitis, but there is little information on the cellular
      localization of cytokines in human skin, particularly during the early phases of
      the inflammatory response to contact allergens. Using in situ hybridization for
      mRNA and immunocytochemistry on biopsies from a series of 16 patients with known
      allergic contact dermatitis, we examined the kinetics of early cytokine
      production after challenge with relevant or irrelevant antigen. We show that
      epidermal keratinocytes from patients challenged in vivo with allergen, but not
      irrelevant antigen, rapidly synthesize (within 4 h) mRNA for interferon-gamma and
      produce immunoreactive interferon-gamma. Interleukin-1alpha and interleukin-8
      mRNA were also detected but showed no correlation with relevant antigen
      challenge. This study demonstrates that keratinocytes can produce interferon
      gamma and that this production is linked to challenge with relevant antigen in
      allergic contact dermatitis. These findings indicate that keratinocytes may
      amplify allergen-specific T-lymphocyte-triggered interferon-gamma dependent
      responses and might partially explain the speed of reaction in this common
      disease and other delayed hypersensitivity reactions involving the skin.

PMID- 8752661
TI  - Adhesive and migratory behaviors of nevus cells differ from those of epidermal
      melanocytes and are not linked to the histological type of nevus.
AB  - It has been postulated that acquired nevi undergo life span continuous evolution
      from junctional, presumably in radial expanding phase at the dermal epidermal
      junction, to compound and then to dermal nested nevi. In an attempt to correlate
      the morphology of nevi with biological data, we have investigated whether
      migratory and adhesive phenotypes of nevus cells could account for histological
      patterns and possible spatiotemporal changes in nevi. Nevus cells were cultured
      from compound and dermal nevi and compared to normal epidermal cultured
      melanocytes from children and adults. AR nevus cells showed similar in vitro
      adhesive and migratory indexes on laminin-1, laminin-5/nicein, fibronectin, or
      collagen IV substrates, suggesting that these intrinsic characteristics do not
      account for the tendency to dermal nesting and/or to radial growth along the
      dermal-epidermal junction. The cells from epidermal and dermal parts of compound
      nevi migrated similarly across a reconstituted basement membrane. The results
      show that intrinsic adhesive and migratory behaviors of nevus cells were not
      associated with a histological type of nevus. Interestingly, differences in
      migratory phenotype and intercellular adhesion capacities between nevus cells and
      normal melanocytes indicated that they could represent different melanocytic cell
      subpopulations. Finally, melanocytes from adults and children expressed similar
      levels of the same integrins as all nevus cells but showed differences in
      function of both alpha3 and alpha6 integrin subunits and in migratory/adhesive
      behaviors, which may suggest different states of melanocyte maturation.

PMID- 8752662
TI  - CD44 expression on epidermal melanocytes.
AB  - We examined CD44 expression on melanocytes to begin to understand what role CD44
      might have in the normal behavior of melanocytes and to provide a basis for
      comparing CD44 expression in melanoma cells. CD44 was expressed on the entire
      surface of melanocytes and accentuated at the tips of dendritic processes. Two
      predominant forms of CD44 are expressed on cultured human foreskin melanocytes.
      One form has the covalent addition of chondroitin sulfate, whereas the other form
      has no chondroitin sulfate. Both use the hematopoietic, or CD44H, core protein.
      Using polymerase chain reaction primers that span the site where alternative
      splicing of CD44 occurs, we found only the cDNA coding CD44H. 12-O
      Tetradecanoylphorbol 13-acetate increases the size of the chondroitin sulfate
      chain(s) attached to CD44 but not the proportion of CD44 molecules that carry
      chondroitin sulfate. Ninety percent of proteoglycans on melanocytes are
      chondroitin sulfate proteoglycans, and the CD44 chondroitin sulfate proteoglycan
      represented 10% of that total. These data show that CD44H is expressed as a "part
      time" chondroitin sulfate proteoglycan on normal cultured melanocytes.

PMID- 8752663
TI  - 1alpha,25-dihydroxyvitamin D3 rapidly inhibits fibroblast-induced collagen gel
      contraction.
AB  - 1alpha,25-Dihydroxyvitamin D3 (1,25-D3) inhibits the proliferation of fibroblasts
      in vitro in monolayer culture. We investigated the effect of 1,25-D3 on normal
      murine and human fibroblasts cultured in collagen type I gels, which more closely
      resembles the in vivo situation in the dermis. In this culture system 1,25-D3 had
      no effect on fibroblast proliferation; however, the fibroblast-induced collagen
      gel contraction was inhibited in a time- and concentration-dependent manner in
      the nanomolar concentration range. 25-Hydroxyvitamin D3 and 24,25
      dihydroxyvitamin D3 were inactive. 1,25-D3 had no effect in fibroblasts lacking a
      functional vitamin D receptor. Pretreatment of fibroblasts in monolayer culture
      for 5 min was sufficient to trigger the inhibition of collagen gel contraction.
      Nifedipine increased collagen gel contraction and counteracted the effect of 1,25
      D3. The inhibition of collagen gel contraction by 1,25-D3 is supposed to be
      mediated by the vitamin D receptor because a functional vitamin D receptor is
      required, and vitamin D metabolites with low affinity to the vitamin D receptor
      were inactive. Brief pretreatment of fibroblasts was sufficient to trigger the
      inhibitory effect of 1,25-D3, suggesting a nongenomic effect. A genomic mode of
      action could not be ruled out, however, because the inhibition was first measured
      after 24 h. The antagonism of the calcium channel antagonist nifedipine probably
      represents the sum of two opposite effects rather than supporting evidence for a
      nongenomic mode of action of 1,25-D3. In conclusion, 1,25-D3 has a specific and
      rapidly triggered inhibitory effect on fibroblast-induced collagen gel
      contraction.

PMID- 8752664
TI  - Abnormal expression of sphingomyelin acylase in atopic dermatitis: an etiologic
      factor for ceramide deficiency?
AB  - Previously, we demonstrated that there is a marked reduction in the amount of
      ceramide in the stratum corneum of both lesional and nonlesional forearms in
      atopic dermatitis (AD), suggesting that an insufficiency of ceramides in the
      stratum corneum is an etiologic factor in atopic dry and barrier-disrupted skin.
      In this study, we investigated, as a possible mechanism involved in the ceramide
      deficiency, whether sphingomyelin (SM) metabolism is altered in AD as compared to
      normal controls. In stripped stratum corneum and biopsied whole epidermis of
      patients with AD, SM hydrolysis as measured at pH 4.7 using [choline-methyl
      14C]sphingomyelin as a substrate were markedly increased by 27- and 7-fold,
      respectively. Radio-thin-layer chromatography of the reaction products revealed
      that, whereas the SM hydrolysis in age-matched normal controls were associated
      with sphingomyelinase (SMase) that degrades SM to yield ceramides and
      phosphorylcholine (PC), most of the SM hydrolysis detected in AD were
      attributable not to the SMase but to a hitherto undiscovered epidermal enzyme, SM
      acylase, which releases free fatty acid and sphingosyl-PC (Sph-PC) instead of
      ceramides. The potential of this acylase-like enzyme to generate Sph-PC through
      SM hydrolysis was corroborated by thin-layer chromatographic analysis of the
      reaction products obtained using porcine kidney acylase, followed by high
      performance liquid chromatography-mass spectrometry. Furthermore, Sph-PC was also
      detected by high-performance liquid chromatography-mass spectrometry after
      incubation of SM with atopic stratum corneum samples. On the other hand, the
      stratum corneum of patients with contact dermatitis or chronic eczema exhibited
      neither increased SM hydrolysis nor the generation of Sph-PC upon radio-thin
      layer chromatographic analysis. These findings suggest that SM metabolism is
      altered in AD, resulting in a decrease in levels of ceramides, which could be an
      etiologic factor in the continuous generation of atopic dry and barrier disrupted
      skin observed in AD.

PMID- 8752665
TI  - Human dermal fibroblast cells express prolactin in vitro.
AB  - This study demonstrates the synthesis and release of prolactin (PRL) from dermal
      fibroblasts (>98%) in vitro, suggesting a potential local source of PRL in skin.
      PRL release was first detected in confluent cultures (0.25 x 10(6) plated cells)
      on or before day 18 and increased to a maximal level of 2 ng/72 h by day 30.
      Medroxyprogesterone acetate and estradiol (E2) had no effect on PRL release, but
      prostaglandin E2 (PGE2) reduced the time required for PRL induction to 6-9 days.
      The steroids and PGE2 together were synergistic, reaching maximal values of
      approximately 10 ng/72 h after 2 or more weeks of treatment. Dibutyryl-cyclic
      AMP, a second messenger in prostaglandin signal transduction, was also
      synergistic with medroxyprogesterone acetate and E2, but induced significant PRL
      expression in the absence of the steroids (28 and 12 ng/72 h, respectively). The
      increase in PRL release was not a result of increased cell proliferation, because
      the PRL-secreting cultures had 32.2 +/- 8.8% less DNA (N = 3 individuals, 93%
      confidence limit) than control cultures after 3 weeks of treatment with dibutyryl
      cyclic AMP, medroxyprogesterone acetate, and E2. Dermal fibroblast PRL was
      immunologically and electrophoretically identical to decidual and pituitary PR
      Ls, and Northern blot analysis demonstrated a PRL mRNA size of 1.15 kb. Maximal
      PRL release from fibroblast cells was 32.0 +/- 6.1 ng/72 h (mean +/- SD at 95%
      confidence limit) for a donor population representing both males (n = 15) and
      females (n = 7) between the ages of 20-week gestation to 52 years. In contrast to
      term decidual fibroblast cells that also express PRL, dermal fibroblasts did not
      co-express insulin-like growth factor-binding protein-1.

PMID- 8752666
TI  - Synchronous measurements of blood pressure and red blood cell velocity in
      capillaries of human skin.
AB  - We have devised a system for analyzing the temporal coherence of capillary
      pressure (CP) and capillary red blood cell velocity (CBV) variations in humans.
      The system is designed to measure human blood pressure in skin capillaries by
      direct cannulation while simultaneously measuring red blood cell velocity in the
      same capillary by video microscopy. The servo-nulling pressure measurement system
      allows the dynamic recording of capillary pressure with a flat frequency response
      of about 12 Hz. Computerized data acquisition is synchronized with the frame code
      of a U-matic video recorder, which records the capillaroscopic picture for later
      computerized off-line analysis of capillary red blood cell velocity. Measurements
      of simultaneously recorded CP and CBV in healthy volunteers show synchronized
      pulsation. Minimal pulsatile variations in CP values result in marked variations
      of CBV. In addition, minor fluctuations (3-4 cycles per minute) in CP are
      accompanied by marked changes in CBV. This system may help provide information
      about microvascular pathophysiology in skin diseases before and after treatment.

PMID- 8752667
TI  - Human keratinocytes express EMMPRIN, an extracellular matrix metalloproteinase
      inducer.
AB  - Increased levels of matrix metalloproteinases are associated with tissue
      degradation and remodeling during tumor invasion and wound healing. In both
      processes, there is evidence that cell interactions between fibroblasts and tumor
      cells or keratinocytes lead to increases in metalloproteinase production. We have
      previously isolated and purified a tumor cell surface protein, EMMPRIN
      (extracellular matrix metalloproteinase inducer), which stimulates production of
      interstitial collagenase, gelatinase A, and stromelysin-1 by fibroblasts, and we
      have obtained cDNA clones that encode the EMMPRIN protein from LX-1 human lung
      carcinoma cells. In this study we report immunolocalization of EMMPRIN around the
      surface of human keratinocytes in vitro and in vivo, and isolation of cDNAs that
      encode the entire open reading frame for EMMPRIN from a human keratinocyte
      library. Comparison of the EMMPRIN cDNAs from normal human keratinocytes and LX-1
      human tumor cells by nucleotide sequence analysis, expression of the recombinant
      proteins, and in vitro translation using the cDNAs from the two sources indicate
      that they express very similar forms of EMMPRIN. Native EMMPRIN isolated directly
      from extracts of keratinocytes, however, is slightly smaller in size and is
      present at a lower concentration compared with that from LX-1 tumor cells. These
      results establish the presence of EMMPRIN in the normal epidermis and raise the
      possibility of its involvement in regulation of matrix remodeling at the
      epidermal-dermal interface.

PMID- 8752668
TI  - Growth regulatory proteins that repress differentiation markers in melanocytes
      also downregulate the transcription factor microphthalmia.
AB  - Expression of basic fibroblast growth factor cDNA or dominantly acting oncogenes,
      e.g., E1A, in immortalized mouse melanocytes leads to autonomous growth in vitro,
      depigmentation, and in the case of the oncogenes, tumorigenesis. Because
      downregulation of pigmentation is a common event in human metastatic melanoma
      cells grown in culture, we determined the molecular basis of depigmentation in a
      mouse melanocyte model system. We tested the effect of E1A mutants deficient in
      their ability to neutralize several regulatory proteins and determined changes in
      melanogenic gene expression. We identified Microphthalmia as the affected,
      downregulated transcription factor in melanocytes rendered amelanotic by E1A,
      basic fibroblast growth factor, or the oncogenes ras or neu, and in an amelanotic
      cell variant of Cloudman S91 mouse melanoma. Against expectations, sequestration
      of p300, a transcriptional adaptor that mediates responses to cyclic adenosine
      monophosphate, was not required for the full transforming effects of E1A. Our
      results suggest that in addition to controlling tyrosinase (albino locus) and
      tyrosinase-related protein 1 (TR-P1/gp75/brown locus), both known to possess the
      DNA consensus site for binding the Microphthalmia protein, this transcription
      factor also controls other melanocyte-specific genes such as pink-eyed dilution
      and Pmel 17 (silver), but not tyrosinase-related protein 2 (slaty locus).
      Furthermore, these findings show that microphthalmia is downregulated not only by
      experimentally introduced dominantly acting oncogenes but also by the aberrant
      expression of basic fibroblast growth factor and by spontaneous tumorigenic
      transformation.

PMID- 8752669
TI  - The gene encoding collagen alpha1(V)(COL5A1) is linked to mixed Ehlers-Danlos
      syndrome type I/II.
AB  - The Ehlers-Danlos syndrome (EDS) is a heterogeneous group of inherited connective
      tissue disorders in which cutaneous fragility and ligamentous laxity often
      combine with vascular, gastrointestinal, and skeletal deformities. There is
      considerable phenotypic overlap between the more common forms of EDS (types I and
      II), in which specific molecular defects have not yet been identified. Recently,
      genetic linkage has been demonstrated between the COL5A1 gene, which encodes the
      alphal chain of type V collagen, and EDS type II in a large British kindred.
      Using a polymorphic intragenic simple sequence repeat at the COL5A1 locus, we now
      demonstrate tight linkage to EDS type I/II in a three-generation family, giving a
      LOD score (log10 of the odds for linkage) of 4.07 at zero recombination. The
      variation in expression in this family suggests that EDS types I and II are
      allelic, and the linkage data support the hypothesis that mutation in COL5A1 can
      cause both phenotypes.

PMID- 8752670
TI  - IgA antibodies in chronic bullous disease of childhood react with 97 kDa basement
      membrane zone protein.
AB  - Chronic bullous disease of childhood (CBDC) is an autoimmune blistering disease
      occurring in prepubertal children. Both CBDC and its adult counter-part, linear
      IgA bullous dermatosis (LABD), are characterized by linear deposition of IgA
      along the cutaneous basement membrane zone (BMZ). Circulating IgA antibody in
      LABD has been found to bind to a 97-kDa BMZ antigen, whereas the antigen in CBDC
      has not been well characterized. The purpose of this study was to evaluate the
      immunoreactivity of BMZ IgA antibodies in a series of CBDC patients. We evaluated
      12 sera from patients with CBDC with circulating IgA anti-BMZ antibodies on
      indirect immunofluorescence (IIF), which stained the epidermal side of split skin
      with titers ranging from 1:20 to 1:640. Immunoblotting was performed against two
      preparations of BMZ proteins: one enriched with the two bullous pemphigoid
      antigens (BP230, BP180) and one enriched with the LABD antigen (LABD97). Eight of
      the twelve sera reacted with a 97-kDa protein that co-migrated with the protein
      detected in many LABD sera. The intensity of the reaction on immunoblot
      correlated with serum antibody titers. There was no consistent pattern of
      reactivity of the IgA anti-BMZ antibodies with either the BP230 or BP180
      antigens, although two sera reacted with several higher molecular mass proteins
      (160-200 kDa). The significance of this reactivity was examined with
      immunoblotting using BMZ-affinity-purified antibodies, and ELF using
      nitrocellulose-eluted antibodies. One serum also contained anti-BMZ IgA
      antibodies that reacted with a 180-kDa protein, corresponding to BP180. We
      conclude that IgA antibodies in CBDC sera recognize a 97-kDa BMZ antigen present
      on the epidermal side of BMZ split skin that co-migrates with the antigen
      previously identified in LABD. These findings suggest that CBDC and LABD are the
      immunologically related disorders occurring in different age groups.

PMID- 8752671
TI  - c-myb proto-oncogene is expressed by quiescent scleroderma fibroblasts and,
      unlike B-myb gene, does not correlate with proliferation.
AB  - Systemic sclerosis (scleroderma) is characterized by excessive deposition of
      extracellular matrix constituents. Although it has been proposed that tissue
      fibrosis is due to increased fibroblast synthesis of various collagen
      polypeptides, there is some experimental evidence that patients with systemic
      sclerosis have a defect in the control of fibroblast growth. The myb family of
      genes includes, among others, the c-myb proto-oncogene and the structurally
      related gene, B-myb, which are both implicated in the regulation of
      differentiation and/or proliferation of hematopoietic and nonhematopoietic cells.
      To elucidate the molecular basis responsible for scleroderma fibroblast
      proliferation, we therefore elected to investigate the expression of c-myb and B
      myb genes in scleroderma and control cells. Using the reverse transcriptase
      polymerase chain reaction technique, we detected c-myb transcripts in scleroderma
      skin fibroblasts rendered quiescent by serum deprivation. Under the same
      experimental conditions, c-myb message was not found in normal skin fibroblasts,
      but, after serum stimulation, c-myb RNA was clearly evident from 3 to 72 h in
      both normal and pathologic cells. Treatment of these cells with c-myb antisense
      oligonucleotides caused downregulation of c-myb expression, and the inhibition of
      scleroderma fibroblast proliferation was 42%, whereas in normal fibroblasts the
      inhibition was weaker (22%). In contrast to c-myb, in normal and scleroderma
      fibroblasts the level of expression of B-myb correlated with cell proliferation
      assessed by cell count, and densitometric analysis showed that B-myb message was
      1.5-5 times higher in most of pathologic cells studied. The antisense B-myb
      oligonucleotides had a weaker antiproliferative effect compared with antisense c
      myb, inhibiting scleroderma and normal fibroblasts by 23% and 13%, respectively.
      These data suggest that the B-myb and c-myb genes may play a role in scleroderma
      fibroblast proliferation and function.

PMID- 8752672
TI  - Improved resolution of magnetic resonance microscopy in examination of skin
      tumors.
AB  - Magnetic resonance imaging has become increasingly important for visualization
      and tissue differentiation of internal organs. Because of limited resolution,
      investigation of skin has been of little diagnostic value so far. We combined a
      homogeneous magnetic field of 9.4 T, as used in magnetic resonance spectroscopy,
      with gradient fields of 11.7 G/cm and an imaging unit to obtain a voxel
      resolution of 40 x 40 x 300 microm(3). With this magnetic resonance microscopy
      unit, we studied normal skin, 12 nevocellular nevi, 20 basal cell carcinomas, 8
      melanomas, and 8 seborrheic keratoses after excision in vitro. The specimens were
      visualized in spin-echo images. The proton relaxation times T1 and T2 were
      determined for the different skin layers and tumor tissues. Interpretation of the
      spin-echo images was based on comparison with the correlating histology.
      Epidermis, dermis, subcutaneous tissue, and hair follicle complexes could be
      distinguished. Stratum corneum and hairs emitted no signal. All tumors presented
      as distinct, signal-rich, homogeneous structures within the dark, signal-poor
      dermis. Their shape corresponded to their outline in the histologic sections.
      Buds of superficial basal cell carcinomas could be resolved. The proton
      relaxation times T1 and T2 were significantly different among all skin layers and
      tumors. Our results demonstrate that with sufficient resolution, differentiation
      of skin tumors is possible using magnetic resonance imaging.

PMID- 8752673
TI  - Human cutaneous dendritic cells migrate through dermal lymphatic vessels in a
      skin organ culture model.
AB  - The capacity to migrate from peripheral tissues, where antigen is encountered, to
      lymphoid organs, where the primary immune response is initiated, is crucial to
      the immunogenic function of dendritic cells (DC). The skin is a suitable tissue
      to study migration. DC were observed to gather in distinct nonrandom arrays
      ("cords") in the dermis upon culture of murine whole skin explants. It is assumed
      that cords represent lymphatic vessels. Using a similar organ culture model with
      human split-thickness skin explants, we investigated migration pathways in human
      skin. We made the following observations. 1) Spontaneous emigration of Langerhans
      cells took place in skin cultured for 1-3 d. Nonrandom distribution patterns of
      strongly major histocompatibility complex class II-expressing DC (cords) occurred
      in cultured dermis. A variable, yet high (>50%) percentage of these DC
      coexpressed the Birbeck granule-associated antigen "Lag." Ultrastructurally, the
      cells corresponded to mature DC. 2) Electron microscopy proved that the dermal
      structures harboring the accumulations of DC (i.e., cords) were typical lymph
      vessels. Moreover, markers for blood endothelia (monoclonal antibody PAL-E,
      Factor VIII-related antigen) and markers for cords (strong major
      histocompatibility complex class II expression on nonrandomly arranged, hairy
      appearing cells) were expressed in a mutually exclusive pattern. 3) On epidermal
      sheets we failed to detect gross changes in the levels of expression of adhesion
      molecules (CD44, CD54/ ICAM-1, E-cadherin) on keratinocytes in the course of the
      culture period. The reactivity of a part of the DC in the dermal cords with
      Birbeck granule-specific monoclonal antibody "Lag" suggests that the migratory
      population is composed of both epidermal Langerhans cells and dermal DC. We
      conclude that this organ culture model may prove helpful in resolving pathways
      and mechanisms of DC migration.

PMID- 8752674
TI  - Cloning of mouse type VII collagen reveals evolutionary conservation of
      functional protein domains and genomic organization.
AB  - Type VII collagen is the major component of anchoring fibrils, attachment
      structures necessary for stable association of the dermal-epidermal basement
      membrane to the underlying dermis. The critical role of the anchoring fibrils in
      providing integrity to the cutaneous basement membrane zone is attested to by
      demonstration of mutations in the type VII collagen gene (COL7A1) in patients
      with dystrophic epidermolysis bullosa. To gain insight into the evolutionary
      conservation of the type VII collagen gene, in this study we have cloned the
      entire mouse type VII collagen cDNA and elucidated the intron-exon organization
      of the corresponding gene, Col7a1. The coding region of the cDNA consists of 8832
      nucleotides encoding a polypeptide of 2944 amino acids with a calculated
      molecular mass of approximately 295 kDa. Computer analysis predicted the presence
      of an 18-amino acid signal peptide. Comparison of the deduced mouse alpha1(VII)
      collagen polypeptide with the corresponding human sequence indicated 84.7%
      identity and 90.4% homology at the amino acid level. In addition, the domain
      organization, including imperfections and interruptions within the collagenous
      domain consisting of Gly-X-Y repeat sequences, was highly conserved. The unit of
      evolutionary period between the full-length human and mouse polypeptides was
      calculated to be 6.5 million years, however, suggesting relatively rapid
      evolutionary divergence in comparison to other collagen genes. Elucidation of the
      intron-exon organization of the mouse Col7a1 gene revealed 118 distinct exons,
      the same number as present in the human gene. These data indicate a high degree
      of structural conservation between the human and mouse type VII collagen,
      supporting the critical role of this collagen as the major component of the
      anchoring fibrils.

PMID- 8752675
TI  - The in situ repair kinetics of epidermal thymine dimers and 6-4 photoproducts in
      human skin types I and II.
AB  - We assessed the in situ time-dependent loss of epidermal thymine dimers and 6-4
      photoproducts in skin types I and II after exposure to two minimal erythema doses
      of solar-simulating radiation on previously unexposed buttock skin. Using
      quantitative image analysis, we evaluated biopsy sections stained with monoclonal
      antibodies. We then made comparisons, in the same volunteers, with unscheduled
      DNA synthesis, which is a direct marker of overall excision repair. Removal of
      thymine dimers was slow (half-life = 33.3 h), with high levels of lesions still
      present 24 h post-irradiation; some lesions were still present at 7 d. In
      contrast, removal of 6-4 photoproducts was rapid (half-life = 2.3 h), the decay
      kinetics of which correlated better with the decline in epidermal unscheduled DNA
      synthesis (half-life = 7.1 h). These data show that as in mouse, monkey, and in
      vitro models, the 6-4 photolesion is repaired preferentially in human epidermis
      in situ. They also raise the possibility that poor thymine dimer repair may be a
      feature of skin types I and II, who are more prone to skin cancer than are types
      III and IV. There was an inverse relationship between the onset of erythema and 6
      4 photoproduct repair, suggesting that this repair process initiates erythema.

PMID- 8752676
TI  - Novel fibroblast-specific monoclonal antibodies: properties and specificities.
AB  - Specific detection of fibroblasts has been one of the unsolved problems in cell
      biology. Because monoclonal antibodies (MoAbs) might provide an easy and
      reproducible method of fibroblast detection, we have produced a panel of MoAbs
      raised against cell surface proteins of human dermal fibroblasts. Using flow
      cytometry and immunohistochemistry, we have shown that two of these MoAbs,
      FibAS01 and FibAS02, react exclusively with human fibroblasts. They do not react
      in vitro with human keratinocytes, endothelial cells, or blood cells.
      Immunohistologic experiments investigating the binding pattern of the MoAbs
      FibAS01 and FibAS02 in cryostat sections of different tissues confirmed the flow
      cytometric results. In human skin, the antibodies exclusively labeled
      fibroblasts. In other human tissues such as lymph nodes, placenta, kidney,
      muscle, thyroid gland, gall bladder, cartilage, and tendon, the specificity for
      fibroblasts was borne out. Neither antibody reacts with fibroblasts from mouse,
      rat, or pig. The isotype was defined as an IgG1 for both. By western blot
      analysis, both antibodies detected a molecule of 60-65 kDa under reducing and
      nonreducing conditions. By immunoelectron microscopy, we observed the antigens on
      the cell surface without any clustering at specific sites. These data demonstrate
      that the two MoAbs, FibAS01 and FibAS02, exclusively recognize human fibroblasts.

PMID- 8752677
TI  - Expression of E and P-cadherin by melanoma cells decreases in progressive
      melanomas and following ultraviolet radiation.
AB  - The purpose of our study was to determine whether the degree of E- and P-cadherin
      expression in melanomas correlates with the invasive behavior of the clinical
      lesions from which the cell lines were derived. Cadherins comprise a family of
      calcium-dependent cellular adhesion molecules expressed on most cell types that
      form solid tissues. In the human epidermis, melanocyte cadherin expression may
      function to maintain the integrity of the epidermal-melanin unit. Employing both
      immunofluorescence microscopy and fluorescence-activated cell sorter analysis, we
      localized and quantitated E- and P-cadherin expression on melanoma cell lines
      derived from primary or metastatic lesions using the monoclonal antibodies HECD-1
      and NNC-CAD-299, respectively. Human epidermal melanocytes isolated from neonatal
      foreskin were evaluated by similar techniques and served as a biologic control.
      Melanoma cell lines were isolated from primary or metastatic lesions of patients
      described as having "early," "intermediate," or "advanced disease." Melanoma E-
      and P-cadherin immunofluorescence, as quantified by fluorescence-activated cell
      sorter, varied inversely with disease progression. Selected log mean ratios of E
      cadherin fluorescence, as compared to human epidermal melanocytes (arbitrarily =
      1), ranged from 1.04 in the WM 35 melanoma cell line (low invasive potential) to
      0.1 and 0.02 in the WM 983A and 1361A melanoma cell lines (derived from primary
      lesions with metastases), respectively. Although values for P-cadherin
      fluorescence were less, the trend of decreasing cadherin amounts with more
      advanced disease was observed. Melanoma cells appear to express E- and P-cadherin
      levels inversely related to disease progression. Ultraviolet radiation
      significantly decreased E- and P-cadherin expression in the human epidermal
      melanocytes and P-cadherin expression in the WM 35 melanoma cell line (p < 0.05).
      Although not statistically significant, E-cadherin expression in the WM 35
      melanoma cell line decreased substantially. Thus, ultraviolet radiation may have
      a direct effect on human epidermal melanocytes and melanoma cell attachment
      through cadherins within the epidermis or tumor nodules.

PMID- 8752678
TI  - Antioxidant enzymes in psoriatic fibroblasts and erythrocytes.
AB  - Antioxidant enzyme activities in fibroblasts and erythrocytes prepared from
      normal and psoriatic patients were measured and compared. The most significant
      differences were noted in superoxide dismutase (SOD) activities. A dramatic (5.2
      fold) increase in Mn-SOD activity along with a lesser (1.8-fold) increase in CuZn
      SOD activity was observed in fibroblasts from lesional and nonlesional psoriatic
      skin. The increase of Mn-SOD activity was correlated with an increase of both
      protein and mRNA. A slight (1.2-fold) increase in CuZn-SOD activity was also
      found in psoriatic as compared to normal red blood cells, while Mn-SOD activity
      was not present in these cells. In contrast, both glutathione peroxidase and
      catalase activities were only slightly (1.3-fold) increased in psoriatic
      fibroblasts, with no appreciable change noted in psoriatic erythrocytes.
      Likewise, glutathione levels were observed to be similar in normal and psoriatic
      cells. The increases in SOD activities did not appear to correlate with the
      severity of the disease as expressed by the Psoriatic Area Severity Index score
      or with plasma inflammatory markers. These results demonstrate that antioxidant
      enzyme activities, particularly Mn-SOD in fibroblasts and CuZn-SOD in
      erythrocytes, are significantly elevated in cells from psoriatic patients.

PMID- 8752679
TI  - Lack of induction of IL-10 expression in human keratinocytes.

PMID- 8752681
TI  - Genetic basis of Bart's syndrome: a glycine substitution mutation in the type VII
      collagen gene.
AB  - Bart's syndrome was initially described as a genodermatosis characterized by
      congenital localized absence of the skin, together with blistering and nail
      abnormalities. Recent analysis of Bart's original kindred demonstrated
      ultrastructural abnormalities in the anchoring fibrils and linkage of the
      inheritance of the disease to the region of chromosome 3 near the type VII
      collagen gene (COL7A1). We have performed mutation analysis in this family by
      using electrophoretic heteroduplex analysis followed by direct nucleotide
      sequencing of DNA. These results disclosed a G-to-A transition within exon 73 of
      COL7A1, which results in a glycine-to-arginine substitution within the triple
      helical domain of type VII collagen in affected individuals. In this family,
      these findings demonstrate that Bart's syndrome is a clinical variant of dominant
      dystrophic epidermolysis bullosa.

PMID- 8752680
TI  - A novel subepidermal blistering disease with autoantibodies to a 200-kDa antigen
      of the basement membrane zone.
AB  - Several components of the basement membrane zone (BMZ) have been identified as
      antigenic targets in autoimmune bullous diseases. We report a novel disease with
      autoantibodies to a BMZ antigen that is different from the targets described so
      far. The patient suffering from this disorder showed tense bullae and severe
      mucous membrane involvement rapidly responding to oral tetracyclines and
      colchicine. Histopathologic findings resembled those of dermatitis herpetiformis.
      Direct immunofluorescence microscopy showed linear deposits of IgG and C3 at the
      BMZ. By indirect immunofluorescence studies on split human skin, using both 1 M
      NaCl and suction blistering for dermal-epidermal separation, IgG antibodies
      localized exclusively to the dermal side of the split. The antibodies were mainly
      of the IgG4 subclass. By Western blot analysis of epidermal and dermal extracts,
      the patient's serum unequivocally reacted with a dermal antigen of 200 kDa. It
      did not recognize bullous pemphigoid antigens, the autoantigen of epidermolysis
      bullosa acquisita, purified preparations of laminin-1 and laminin-5, or the
      recently described 105-kDa BMZ antigen. By immunoblotting of concentrated
      conditioned SCC-25 medium, the patient's antibodies reacted with a band of 200
      kDa and several hands of lower molecular weight. No reactivity was seen with
      extracts of cultured human fibroblasts. By indirect immunogold electron
      microscopy, immunoreactants localized to the lower lamina lucida. After clearance
      of skin lesions, both indirect immunofluorescence and Western blot analysis
      became negative. This patient suffers from a novel autoimmune bullous disease
      with autoantibodies to a 200-kDa antigen of the BMZ.

PMID- 8752682
TI  - [Double filtration and immunoadsorption plasmapheresis in Guillain-Barre
      syndrome].
AB  - We studied the effect of double filtration and immunoadsorption plasmapheresis in
      Guillain-Barre syndrome retrospectively in 70 patients. Thirty three patients had
      plasmapheresis, of whom 23 had double filtration and 10 immunoadsorption. The
      rest of 37 patients consisted of a control group. Clinical disability was
      evaluated using the functional grading scale by Hughes. In patients having a
      maximum disability of grade 4 and 5, the double filtration plasmapheresis group
      showed statistically significant improvement at 3 months after the treatment.
      There was no significant difference in prognoses between the immunoadsorption
      plasmapheresis and control groups. In mildly-illed patients having grade 2 and 3,
      the prognoses were not different between the three groups. In Guillain-Barre
      syndrome, double filtration plasmapheresis, as well as well-established plasma
      exchange, had benefit for severely-illed patients.

PMID- 8752683
TI  - [Corticobasal degeneration: a combined clinical, PET and pathological study].
AB  - We report 2 cases of corticobasal degeneration (CBD) with reference to the
      clinical and pathological features and neuroimaging including MRI, positron
      emission tomography (PET) and single photon emission tomography (SPECT). Case 1
      was a 66-year-old right-handed woman. Her spontaneity had been gradually
      impaired, and she showed a progressive course of naming difficulty, memory
      disturbance, and right unilateral spatial neglect in addition to the right hemi
      parkinsonism and bilateral pyramidal tract signs. Cortical and subcortical
      atrophy was predominant in the left hemisphere on MRI. As compared with the right
      side, both cerebral blood flow (CBF) and oxygen metabolism (CMRO2) were decreased
      in the left hemisphere on the PET which was performed 4 years after onset. She
      showed further clinical deterioration, and exhibited a bilateral parkinsonism 6
      years after the onset. The follow-up SPECT revealed diffusely bilateral
      hypoperfusion except for the basal ganglia and occipital lobes 6 years after the
      onset. Case 2 was a 56-year-old right-handed woman. She exhibited a progressive
      course of bilateral parkinsonism, hallucinations and vertical eye movements
      disturbance. She died of infection 42 months after the onset of the initial
      symptoms. Bilateral frontal atrophy was seen on X-ray CT and MRI. PET revealed a
      diffuse moderate decrease in CBF and CMRO2 particularly in the frontal cortex,
      central semiovale, paraventricular white matter and cingulate gyrus bilaterally.
      Pathological examination disclosed a mild frontal atrophy, and there was diffuse
      neuronal loss, gliosis, and achromasia in the cerebral cortices. There was
      moderate neuronal cell loss and gliosis in the thalamus, whereas the globus
      pallidus, striate and substantia nigra were severely affected. Neuronal
      inclusions termed corticobasal inclusions were present in the substantia nigra,
      nuclei raphes, and Meynert's nuclei, and none of these regions contained Pick's
      cell. PET and SPECT studies revealed an asymmetrical decrease in CBF and CMRO2 in
      the initial stage and diffuse bilateral decrease in the advanced stage in Case 1,
      whereas Case 2 showed a bilateral decrease in the late stage. This may indicate
      that the patterns of hypoperfusion and/or hypometabolism differs according to the
      clinical stages of CBD.

PMID- 8752684
TI  - [Imaging and pathological studies on the esophageal dysfunction in patients with
      myotonic dystrophy].
AB  - The purpose of this study is to clarify a correlation between the esophageal
      dysfunction and suffocation after meals in patients with myotonic dystrophy (MD)
      and to find how to prevent such accidents. Using imaging methods, we examined
      eight patients with MD (six of them had difficulty in swallowing), four patients
      with other neuromuscular diseases (Fukuyama-type congenital muscular dystrophy,
      congenital myopathy, Machado-Joseph disease, and Duchenne's muscular dystrophy),
      and two healthy control subjects. We also investigated material from an autopsy
      of another patient with MD who died of suffocation. In all patients with MD,
      fluoroscopy and computed tomography showed dilatation of the esophagus,
      particularly in the proximal third, and residual contrast media in the esophagus
      15 to 40 minutes after swallowing. In histologic studies, morphologic changes
      were confined to the esophageal striated muscle in a patient with MD. These
      results indicate that regurgitation from the esophagus to the trachea happens
      more than 40 minutes after swallowing in patients with MD and that histological
      alterations of striated muscle are primary causes of the esophageal dysfunction.
      From these findings, we propose that patients with MD should not lie down at
      least 40 minutes after meals whether they complain of difficulty in swallowing or
      not.

PMID- 8752685
TI  - [A case of agammaglobulinemia with chronic enteroviral meningomyelitis].
AB  - We report a 30-year-old man with agammaglobulinemia and chronic aseptic
      meningomyelitis. The patient was diagnosed as having X-linked recessive
      agammaglobulinemia at 4 years of age and gammaglobulin supplementation was
      started. He had TIA-like episodes several times since 25 years of age. He
      developed difficulty in micturition and impotence at 29 years of age.
      Neurological examination revealed bilateral deafness, contracture of knee joints,
      slight weakness and areflexia in the lower extremities, Babinski sign and
      dysuria. There was sensory disturbance in the lower extremity on the left. There
      was not consciousness disturbance or meningeal irritation sign. The cerebrospinal
      fluid findings included pleocytosis and increase in protein. Enterovirus RNA was
      detected in the cerebrospinal fluid by the modified polymerase chain reaction
      (PCR) method. MRI of lower spinal cord showed syrinx formation in the lumbosacral
      cord and CT of the brain showed bilateral temporal lobe atrophy and
      temporoparietal subdural fluid collection on the left. 123I-IMP SPECT showed
      decrease in the cerebral blood flow in the whole brain. EEG showed diffuse slow
      activity, suggesting the subclinical encephalopathy. Chronic enteroviral
      meningoencephalitis with agammaglobulinemia (CEMA) is one of the complications of
      agammaglobulinemia. However, myelitis without apparent encephalopathy is very
      rare. To our knowledge, there have been no reports of spinal sylinx formation in
      CEMA.

PMID- 8752686
TI  - [A case of cerebral infarction due to dissection in a branch of the middle
      cerebral artery].
AB  - A 65-year-old man developed left drop hand, dysarthria and emotional
      incontinence. Brain CT and MRI revealed multiple cerebral infarctions in the
      cortex and subcortical white matter of the right temporal and parietal lobes
      which were in the distribution of the right middle cerebral artery. Cerebral
      angiography disclosed segmental narrowing (string sign) and two pseudoaneurysms
      in the right angular artery which were diagnosed as dissecting aneurysm of a
      branch of the middle cerebral artery. In this case, cerebral angiography was more
      useful than MRI in diagnosis of dissecting aneurysm of a branch of the middle
      cerebral artery. This was a very rare case of dissecting aneurysm of the middle
      cerebral artery localized in one of its branches.

PMID- 8752687
TI  - [Systemic vascular change associated with moyamoya-like cerebrovascular disease
      and microvascular coronary artery disease].
AB  - A 34-year-old man with hypertension and diabetes mellitus developed dizziness and
      visited our institute. He had history of headache with numbness of the right hand
      since age 15 years and left occipital lobe infarction at age 28 years. The
      cerebral angiogram showed several changes peculiar to advanced stage of moyamoya
      disease (spontaneous occlusion of the circle of Willis), i.e. segmental stenoses
      or occlusions of bilateral internal carotid arteries, left vertebral artery and
      left posterior cerebral artery with abnormal vascular networks at the bilateral
      basal ganglia. He was also diagnosed to have asymptomatic ischemic heart disease.
      The coronary angiogram showed diffuse sclerotic lesions of left anterior
      descending and right coronary arteries without significant stenosis, which
      suggested the presence of microvascular lesion as a cause of myocardial ischemia.
      Coronary disease has been rarely reported as a complication of moyamoya disease,
      and microvascular coronary artery disease has never been described. Moyamoya
      disease should be regarded as a part of systemic vascular disorders, and the
      evaluation of extracerebral cardiovascular system is necessary to clarify
      pathophysiology of this disease.

PMID- 8752688
TI  - [Removal ability of IgG anti-GQ1b antibody in immunoadsorption therapy for Fisher
      syndrome--comparison of the removal ability between tryptophane column and
      phenylalanine column].
AB  - Anti-GQ1b antibody seems to be a pathogenetic factor in the development of Fisher
      syndrome (FS). Although several patients received immunoadsorption therapy (IAT),
      whether it can remove the autoantibody has not yet been clarified. We treated two
      patients with FS by IAT using tryptophane column (TR-C) and phenylalanine column
      (PH-C) (TR-C; 9 times altogether in 2 patients, PH-C: twice altogether in 2
      patients), and compared the removal ability of IgG anti-GQ1b antibody and
      immunoglobulin between TR-C and PH-C. TR-C removed the IgG anti-GQ1b antibodies,
      IgG, IgA and IgM more than PH-C did. TR-C removed the IgG anti-GQ1b antibody more
      selectively than non-specific immunoglobulin. In practicing IAT on FS, the use of
      TR-C rather than PH-C is recommended in view of the removal ability of the
      autoantibody.

PMID- 8752689
TI  - [An adult case of homocystinuria probably due to methylenetetrahydrofolate
      reductase deficiency--treatment with folic acid and the course of coagulation
      fibrinolysis parameters].
AB  - We report a rare male case of homocystinuria probably due to
      methylenetetrahydrofolate-reductase deficiency. The onset of his disorder was at
      19 years of age, and he had no family history. He initially developed gait
      disturbance, and then generalized seizure in several months, which made him
      admitted to our hospital. Neurological examinations revealed mental dysfunction,
      spastic paraplegia, cerebellar ataxia, and sensory disturbance in his feet. MRI
      showed multiple increased intensities on T2-weighted images in the cerebral white
      matter. EMG revealed neurogenic changes. These symptoms and signs slowly
      progressed, and he then developed thrombophlebitis in his lower extremities.
      Thrombin-antithrombin III complex (TAT) and D-dimer remained high continuously,
      and plasma homocysteine level was more than ten times higher than the normal
      range. Plasma cystathionine level was high and methionine level was low. The
      serum folic acid, vitamin B12, and methylmalonic acid in the urine were normal.
      Megaloblastic anemia was not seen. Based on these data, he was diagnosed to have
      homocystinuria probably due to methylenetetrahydrofolate-reductase deficiency.
      Treatment with high doses of folic acid, pyridoxine and cobalamin normalized
      plasma cystathionine and methionine levels, and markedly decreased plasma
      homocysteine, although it remained about three times higher than the normal
      range. Thereafter, both TAT and D-dimer levels also markedly decreased. The
      administration of folic acid reduced elevated plasma homocysteine as well as the
      coagulation--fibrinolysis factors. This implies that they may serve as useful
      markers for effective treatment of this disease.

PMID- 8752690
TI  - [Familial Binswanger-type encephalopathy with Sneddon syndrome].
AB  - We reported a family with early onset cerebrovascular disease. Patient 1 (a 36
      year-old man) demonstrated a combination of livedo reticularis and cerebral
      infarction as previously described as Sneddon syndrome. He also showed transient
      focal neurologic symptoms and mild dementia. Patient 2 (an elder sister of
      Patient 1) was suffering from migraine. Their father and paternal uncle died of
      cerebral infarction, which had developed in their thirties or forties. Patients 1
      and 2 showed MRI findings compatible with encephalopathy with Binswanger-type.
      Contrary to the previous reports on Binswanger-type encephalopathy, both of these
      patients demonstrated decreased levels of fibrinogen as well as those of factor
      V, together with negative antiphospholipid antibody. Thus, juvenile onset,
      autosomal dominant inheritance, the diversity of clinical findings and the
      coagulopathy in this family were characteristic features. The level of thrombin
      antithrombin III complex (TAT) was markedly increased in Patient 1. Treatment
      with antithrombin (argatroban 20mg i.v. everyday for 28 days) not only reduced
      the level of TAT but also improved the livedo reticularis and neurological
      findings. Although gene analysis has not been performed yet on this family, this
      condition is similar to cerebral autosomal dominant arteriopathy with subcortical
      infarct and leukoencephalopathy (CADASIL), which involve juvenile cerebral
      infarction and dementia as well as migraine.

PMID- 8752692
TI  - [A case of diaphragmatic paralysis following herpes zoster].
AB  - We report a case of diaphragmatic paralysis after herpes zoster. A 82-year-old
      woman developed shortness of breath on effort after about two months of a typical
      herpes zoster eruptions affecting the C4 and C5 dermatomic areas on the right
      side. A chest x-ray showed an elevated right diaphragm. The diaphragmatic evoked
      potential by stimulation of the right phrenic nerve at the posterior border of
      the sternocleidomastoid muscle was not elicited. Chest CT and cervical MRI were
      normal. The viral antibody titers of herpes zoster were elevated in the serum.
      Cervical herpes zoster should be considered as a possible cause of
      hemidiaphragmatic paralysis.

PMID- 8752691
TI  - [A case of familial amyotrophic lateral sclerosis with markedly decreased
      accumulation on 123I-MIBG myocardiac scintigraphy and atonic bladder].
AB  - A 63-year-old Japanese woman with familial amyotrophic lateral sclerosis (ALS)
      showed cardiac hypofunction and neurogenic bladder. Her autonomic function was
      evaluated by means of 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy
      and urodynamic study. (1) MIBG scintigraphy: Both early and late imagings showed
      severe defects of myocardial 123I-MIBG accumulation despite the normal
      accumulation of 201thallium. (2) Urodynamic study: Atonic bladder was observed on
      cystometry. These data indicate that both sympathetic and parasympathetic nerve
      functions were disturbed, suggesting the possibility that autonomic disturbance
      in familial ALS may differ from those in sporadic ALS, in which increased
      sympathetic nervous function has been reported.

PMID- 8752693
TI  - [A case report of thoracic aortic and common carotid artery dissecting aneurysm
      diagnosed by duplex ultrasound examination].
AB  - A 61-year-old man was admitted to our hospital because of sudden consciousness
      disturbance, aphasia and right-side hemiparesis. On admission his blood pressure
      was 124/74mmHg, and his pulse was a regular rate of 46 beats per minute.
      Electrocardiogram was normal. Thirty minutes after the onset brain computed
      tomographic (CT) scan showed no abnormality. Fifty minutes after the onset
      cervical ultrasound examination with color-coded Doppler demonstrated a
      subintimal dissection with a false channel of the left common carotid artery.
      Eighty minutes after the onset thoracic CT scan demonstrated the false lumen in
      ascending and descending thoracic aortic artery. Cervical CT scan showed a
      dissection with a false channel of the left common carotid artery. We could
      diagnose him as cerebral infarction due to thoracic aortic and common carotid
      artery dissection by means of ultrasound examination within 80 minutes after the
      onset. He spontaneously and fully recovered three days later. We emphasize the
      usefulness of noninvasive technique such as cervical ultrasound examination with
      color-coded Doppler in the diagnosis and follow-up of common carotid artery
      dissection.

PMID- 8752694
TI  - [Late-onset adrenomyeloneuropathy perplexed with spondylosis. A case report].
AB  - We reported a 60-year-old man with late-onset adrenomyeloneuropathy (AMN). He had
      been well until 10 years before entry, when he noticed numbness in the legs with
      gait difficulty; symptoms worsened gradually with additional urinary disturbance.
      Transient improvement occurred after cervical and lumbar spinal operation under
      the diagnosis of spinal spondylosis, while his spastic gait got worse.
      Neurological examination on admission disclosed bilateral horizontal nystagmus,
      ataxic and spastic gait, increased patellar tendon reflexes, Chaddock sign, and
      impaired deep sense in the lower limbs with positive Romberg sign. Abnormal
      laboratory data included hypofunction of the adrenal cortex and elevated
      saturated very long chain fatty acids (VLCFAs). Serum cholestanol level was
      normal and anti-HTLV-1 antibody was negative. T2-weighted MRI showed a high
      signal intensity lesion in the occipital white matter along the optic radiation.
      Electrophysiological tests suggested a brainstem lesion on auditory brainstem
      response, thoracic or lumbar lesion on somatosensory evoked potential, and
      peripheral neuropathy on nerve conduction study. In the present case, it should
      be emphasized that the determination of serum VLCFAs unveiled the diagnosis of
      AMN in old patients with spinal spondylosis or without apparent clinical symptoms
      of adrenocortical insufficiency.

PMID- 8752695
TI  - [Tracheal deformity observed in tracheostomized Duchenne muscular dystrophy
      patients who can speak with appropriately inflated cuff of tracheal tube].
AB  - Respiratory failure occurring during late adolescence is a major cause of death
      in Duchenne muscular dystrophy (DMD). A number of respiratory assistance
      techniques including tracheostomy and positive pressure mechanical ventilation
      have been utilized not only to prolong DMD patients' life but also to improve
      quality of their life. It is surprising that most of the tracheostomized DMD
      patients can speak under positive pressure ventilatory assistance. Preserved
      functions of glosso-pharyngo-laryngeal muscles in these patients presumably make
      it possible to control the air leak around tracheal tube, which does not
      necessitate tight inflation of the tube cuff. Recently we noticed that some
      patients are still able to speak even when the cuff is fully inflated. In order
      to understand the mechanism of this phenomenon, we visualized the topographical
      relationship between trachea and the tube cuff using computed tomography by
      filling the cuff with aqueous contrast medium. We obtained following findings: 1)
      Trachea is flat and deviated from normal midline position, and 2) the tube cuff
      is located eccentrically in trachea resulting in compression of one side of the
      inner wall and leaving open space on the other side. We conclude that the
      tracheal malposition and deformity underlie this strange phenomenon and tight
      inflation of the cuff to prevent air leak may result in unfavorable complications
      in DMD patients.

PMID- 8752696
TI  - [Mononeuritis multiplex associated with measles virus infection].
AB  - We describe a 19-year-old patient who developed mononeuritis multiplex associated
      with measles virus infection. On April 30th, 1995, he suffered from fever and
      skin eruption, which disappeared ten days later. Thirteen days later, he noticed
      weakness of the fingers of both hands and forearms, and pain on both elbow
      joints. He was admitted to our hospital on June 12th, 1995. Neurologic
      examination revealed weakness and sensory disturbance, confined to the distal
      aspects of the right radial nerve and left median nerve. The electrodiagnostic
      findings confirmed those of axonal neuropathy in the right radial and left median
      nerves. Routine laboratory studies were normal. The cerebrospinal fluid test and
      EEG were normal. The IgG and IgM antibody titers against measles virus continued
      to be elevated in serum over four months after the onset, while they were not
      elevated in the cerebrospinal fluid. The corticosteroid therapy was mildly
      effective. Although the pathogenesis of this case is unclear, we speculate that
      the mononeuritis multiplex was caused by vasculitis related to the persistent
      measles virus infection in both elbow areas.

PMID- 8752697
TI  - [Changes in NK activities and TGF- beta concentrations in the peritoneal cavity
      in endometriosis and their interaction related with infertility].
AB  - The purpose of this study was to clarify the relationship between NK activity and
      TG-beta in the immune system in endometriosis. We investigated (1) the changes in
      the NK activity and concentration of TGF-beta in human peritoneal fluid (HPF),
      and (2) the effects of HPF and TGF-beta on the development of early mice embryos.
      In a rat model of experimental endometriosis, we observed the effects of tissue
      culture supernatants of peritoneum on NK activity in rat spleen cells, and
      obtained the following results. (1) NK activity of peripheral lymphocytes in
      healthy women was significantly suppressed in the presence of HPF of
      endometriosis. (2) The concentrations of TGF-beta was significantly higher in HPF
      of endometriosis than in HPF of healthy women. (3) Both HPF of endometriosis and
      TGF-beta significantly inhibited the development of early mice embryos. (4) The
      supernatants prepared from the intact peritoneum of the rat model showed marked
      inhibition of NK activity compared to control rats, although the peritoneum was
      obtained from a region distant from the implanted endometrium. These results
      suggest that ectopic endometrial tissues may cause a change in the cell-mediated
      immune system and subsequently exert an adverse effect on human reproduction.

PMID- 8752698
TI  - [Expression of the small molecular weight matrix metalloproteinase in adenomyosis
      of the mouse uterus].
AB  - The etiology and the pathogenesis of adenomyosis, which is a benign disease
      featuring ectopic proliferation and invasion of the endometrial stromas and
      glands into the myometrium, as seen with malignant tumor cells, are still
      unknown. Adenomyosis induced in mice by intrauterine pituitary isografts was
      analyzed to study the relationship between adenomyosis and matrix
      metalloproteinase. Under zymography, adenomyosis showed a gelatiolytic band of 20
      30kDa, which was inhibited by EDTA. We then compared matrix metalloproteinase,
      which is a small protein, with the known pump-1 (MMP7) utilizing RT-PCR and
      southern blotting hybridization. The PCR product from pump-1 mRNA was clearly
      detected in both adenomyosis and normal uterus, as in postpartum uterus and
      kidney in which pump-1 is expressed. These results were confirmed by southern
      blotting hybridization, and closely resembled the results obtained with RT-PCR.
      Our study suggests that the small molecular weight matrix metalloproteinase,
      which is virtually identical to pump-1, may play important roles in adenomyosis
      at the level of gene transcription, activation, inhibition or otherwise.

PMID- 8752699
TI  - [Involvement of stimulatory effect of prostaglandin F2 alpha on superoxide
      radical production by macrophages in corpus luteum regression].
AB  - The effect of prostaglandin F2 alpha (PGF2 alpha) on superoxide radical
      production by macrophages was studied in pseudopregnant rats. Peritoneal
      macrophages prepared on day 7 or 13 of pseudopregnancy (psp) were incubated with
      various doses of PGF2 alpha for 90 min, and the production of superoxide radical
      was measured by the cytochrome C reduction method. PGF2 alpha significantly
      stimulated superoxide radical production by macrophages on day 13 of psp, but not
      on day 7 of psp. The pretreatment of macrophages with an inhibitor of protein
      kinase C (H7), Ca2+ channel blocker (Verapamil), Ca2+ chelators (EGTA, BAPTA),
      and an inhibitor of GTP-binding protein (pertussis toxin) prevented the
      stimulatory effects of PGF2 alpha on superoxide radical production. In
      conclusion, PGF2 alpha stimulated superoxide radical production by macrophages
      through the intracellular signal transduction pathway including activation of
      protein kinase C through the GTP-binding protein and Ca2+ influx, which would
      play important roles in the luteolytic process in psp rats.

PMID- 8752700
TI  - [Changes in bone mineral content and bone metabolism during pregnancy and
      puerperium].
AB  - In order to clarify the bone metabolism of women during both pregnancy and
      puerperium, we studied the changes in bone mineral content and bone biochemical
      parameters. Bone mineral content was measured by ultrasound bone densitometry,
      and serum calcium (Ca), ionized calcium (i-Ca), intact parathyroid hormone (i
      PTH), intact osteocalcine (i-OC), urinary pyridinoline (Pyr) and
      deoxypyridinoline (D-Pyr) were measured concomitantly. 1. In the 3rd trimester
      bone stiffness was decreased (p < 0.05) compared the 1st and 2nd trimesters, but
      was slightly increased in the puerperal group. 2. Serum i-OC was decreased during
      pregnancy but significantly increased (p < 0.01) in the puerperium. The
      Pyr/Creatinine (Cre) and D-Pyr/Cre ratios were both increased in pregnant and
      puerperal women. 3. Serum Ca, i-Ca and i-PTH were within the normal range during
      pregnancy and the puerperium. These results suggest that in the 2nd and 3rd
      trimesters bone resorption would be increased, and in the puerperium bone
      formation would be increased. In pregnant and puerperal women serum Ca, i-Ca and
      i-PTH are within the normal range, but the turnover rate for Ca metabolism would
      be relatively increased.

PMID- 8752702
TI  - [Simplified avidity assay of rubella IgG antibody in rubella virus infection].
AB  - Simplified avidity assay of rubella IgG antibody with urea was evaluated to
      distinguish primary rubella from reinfection. In this method urea washing was
      done once for 10 minutes. The avidity index (AI) was calculated as the optical
      density percentage for the urea-washed well when compared to that of the non
      treated well. We examined 292 sera from 50 patients with primary infection
      collected 6 to 2,259 days after the rash appeared, 29 sera from 11 patients with
      rubella reinfection and 69 sera from 68 pregnant women without fetal infection
      and having a high hemagglutination inhibition (HI) antibody. In primary infection
      AI increased gradually from 0%, and reached a plateau of about 60% four months
      after the rash appeared, whereas the mean AIs of patients after reinfection and
      with high HI antibody were as high as 87.1% and 89.9%, respectively. These
      results indicate that the simplified avidity assay in rubella IgG antibody is
      also valuable in diagnosing recent primary rubella in pregnant women with a high
      HI antibody.

PMID- 8752701
TI  - [Quantitative changes in leukotriene B4 release in neutrophilic leukocytes
      activated by Ca ionophore during pregnancy--normal pregnancy and preeclampsia].
AB  - The amount of Leukotriene B4 (LTB4) released from neutrophilic leukocyte
      activated by calcium ionophore was measured to examine neutrophilic functions
      regarding the changes during normal pregnancy and differences between normal
      pregnant women and preeclamptic women. In addition, we examined the arachidonic
      acid (AA) content and fatty acid composition of neutrophilic phospholipid in
      normal pregnant women. In a normal pregnancy, the amount of LTB4 released
      decreased significantly with gestation. In preeclamptic women, the amount of LTB4
      released was significantly higher than that in normal pregnant women, but there
      was no significant difference from non-pregnant women. Normal pregnant women
      showed a significantly decreased AA content with gestation. Regarding other fatty
      acids, as to fatty acid composition, there was increased saturated fatty acid and
      decreased unsaturated fatty acid with gestation. The results suggested that the
      LTB4 released was inhibited more in pregnant women than in non-pregnant women,
      and pregnant women also had decreased AA content. In addition, changes in fatty
      acid compositions showed signs of decreased fluidity of the cell membrane. This
      phenomenon is thought to be due to a mechanism to inhibiting the activation of
      neutrophilic leukocytes accompanied by a decrease in the amount of LTB4 released.
      Conversely, no similar inhibition was observed in preeclamptic women, and the
      failure of this mechanism seemed to contribute to the development of
      preeclampsia.

PMID- 8752703
TI  - [A study on the plasma fibrinogen decrease induced by danazol].

PMID- 8752704
TI  - [A case of pregnancy complicated with myelodysplastic syndrome].

PMID- 8752705
TI  - [A case of primary gestational ovarian choriocarcinoma].

PMID- 8752706
TI  - [A case report of pregnancy complicated with adult Still's disease].

PMID- 8752707
TI  - [Placental site trophoblastic tumor of the uterus: usefulness of 3-dimentional
      computed tomography in diagnosis].

PMID- 8752708
TI  - [Recent progress in treatment of osteoporosis].
AB  - Osteoporosis is a multifactorial disease. Understanding the genetic and
      environmental background of this disease is essential for prevention and
      treatment. We examined the relationship between polymorphisms of the estrogen
      receptor gene, bone mineral density, and markers of boe metabolism in
      postmenopausal women. Restriction fragment length polymorphisms of the estrogen
      receptor (ER) gene and its relation to bone mineral density were examined in 238
      postmenopausal healthy women (66.7 +/- 0.9 yr, mean +/- standard error of the
      mean) in Japan. In those with the PPxx genotype, Z score values of bone mineral
      density were significantly lower than those for other genotypes (lumbar spine; p
      = 0.005, total body; p = 0.013). Dinucleotide repeat polymorphisms in the
      upstream region of ER gene were related to bone mineral density and to bone
      metabolic markers. These data suggest that some variation of the ER gene linked
      to these genetic markers is associated with the pathogenesis of postmenopausal
      osteoporosis. In addition, we focused on the role of vitamin K as a nutritional
      factor for bone metabolism. Japanese fermented beans, Natto, contain larage
      amounts of vitamin K2. We found a significant positive correlation between the
      level of vitain K2 in serum and the habit of eating Natto in postmenopausal women
      in the Toyo area. Natto may contribute to the prevention of osteoporosis.

PMID- 8752709
TI  - [Hypertension].

PMID- 8752710
TI  - [Clinical characteristics and therapeutic strategy for acute myocardial
      infarction in the elderly].
AB  - Many randomized studies have revealed that reperfusion therapy is an epochmaking
      treatment for acute myocardial infarction (AMI). However, it is no clear whether
      it is equally beneficial in the elderly or not. In this study, we elucidated the
      clinical characteristics and effectiveness of reperfusion therapy and discussed
      the optimal treatment for AMI in the elderly. The study population comprised
      1,891 consecutive patients with AMI. The reinfarction rates and the rates of
      Killip class III or IV on admission increased with age. The mortality was
      significantly higher in the older subgroups. In the patients with first AMI
      within 24 hours of the onset and who underwent emergency catheterization, those
      accompanied by hypercholesterolemia or with habitual smoking were significantly
      fewer in the older group. Although the Q-wave MI rate, the peak CPK level and the
      reperfusion rate were no different, the low cardiac output condition, multi
      vessel disease and short-term mortality were significantly greater in the older
      group. The patients over 80-year-old were subdivided into three groups; those
      treated conventionally (G-C), those treated with intracoronary thrombolysis (G-T)
      and those treated with direct PTCA (G-A). The overall mortality did not differ
      among the three groups. However, in patients hospitalized after 1990, the
      mortality in G-A was significantly lower than in G-C. The prevalence of bleeding
      complications between G-A and G-T did not differ. The patients in G-A showed
      greater improvement of the left ventricular wall motion and lower incidence of
      postinfarctional angina than other groups. Reperfusion therapy by direct PTCA
      appears to be the optimal strategy for treatment of elder patients with AMI.

PMID- 8752711
TI  - [New vistas in the treatment of Parkinson disease].

PMID- 8752712
TI  - [Urinary incontinence].

PMID- 8752713
TI  - [Laparoscopic surgery in the elderly].

PMID- 8752714
TI  - [Double cancer in elderly patients with hematologic malignancies].
AB  - The occurrence of multiple malignancy was studied in 674 patients with
      hematologic malignancies who were admitted to this department during the past 10
      years. Of the 674 patients, 205 were aged 65 years or older, and 56 (8.3%) had
      another cancer. The frequency of multiple malignancy was significantly higher in
      older patients than in younger patients: 44 (21.5%) vs. 12 (2.6%). The major
      hematologic conditions in patients with multiple malignancy were multiple
      myeloma, myelodysplastic syndromes, non-Hodgkin's lymphoma, and chronic
      myelogenous leukemia. The major sites of cancers other than hematological
      malignancies were the stomach, colon, breast, and esophagus. Many of the older
      patients had gastric cancer or colon cancer, and gastric cancer was common in the
      younger patients. The multiple malignant neoplasms were synchronous in as many as
      20 of the 44 older patients. There was only one such case among the younger
      patients. Of the 56 patients, nine had received alkylating agents, and one has
      received etoposide. In brief, elderly patients with hematologic malignancies are
      likely to have multiple malignant neoplasms. If they are synchronous, the
      patient's prognosis may be adversely affected, because simultaneous management of
      multiple malignant neoplasms is not easy.

PMID- 8752715
TI  - [Ischemic stroke in elderly patients with paroxysmal atrial fibrillation].
AB  - We compared the rate of ischemic strokes in elderly patients (those aged 65 years
      or more) who had paroxysmal atrial fibrillation (E-PAf) with those of younger
      patients (less than 65) with paroxysmal atrial fibrillation (Y-PAf) and of
      elderly patients with chronic atrial fibrillation (E-CAf) in a retrospective
      study. A total of 95 E-PAf patients (mean age 73.6), 79 Y-PAf patients (mean age
      52.4), and 95 E-CAf patients (mean age 73.6) were studied. The incidence of all
      ischemic strokes in E-PAf patients (4.8%/yr) was significantly lower than in E
      CAf patients (8.3%/yr) and higher than in Y-PAf patients (2.5%/yr) (p < .01). We
      found the same tendency in the occurrence of brain embolism. Brain embolism
      occurred in 2.7% of E-PAf patients per year which was significantly lower than in
      E-CAf patients (5.1%/yr) and higher than in Y-PAf patients (1.3%/yr) (p < .01). E
      PAf patients suffered more brain thrombosis than Y-PAf patients, but they had
      nearly the same incidence as did E-CAf patients. Fifty-seven E-PAf patients had
      only one attack of atrial fibrillation and the remaining 38 had more than two
      attacks. Patients with many attacks of atrial fibrillation had significantly
      higher rate of brain embolism than did those who had only one attack (4.6 v.s.
      0.8%/yr) (p < .005). Those two groups did not differ with regard to the rate of
      brain thrombosis.

PMID- 8752716
TI  - [A case of endocrine cell carcinoma in the duodenal bulb].
AB  - A 73-year-old man was admitted to our hospital due to weight loss and melena.
      Roentgenograms and endoscopy showed a Borrmann type 2 tumor occupying the entire
      duodenal bulb. Histological findings of the lesion (H-E stain) showed poorly
      differentiated adenocarcinoma. Almost the entire specimen showed positive
      staining granules for Grimelius stain. Ultrastructurally, remarkable endocrine
      granules covered a layer of the limited membrane (membrane-bound granule) in the
      tumor cell. We diagnosed endocrine cell carcinoma. Since it was difficult to
      operate due to age and invasion to the fundus of the gall-bladder and the
      pancreatic head, we treated this case by chemotherapy.

PMID- 8752717
TI  - [Familial hypertrophic cardiomyopathy generating a marked left ventricular
      pressure gradient in an 82-year-old woman].
AB  - Familial nonobstructive hypertrophic cardiomyopathy in 78-year-old woman was
      diagnosed in 1988. Since then she has been treated with a beta-blocking drug and
      a calcium antagonist. Her clinical condition was NYHA I or II for several years.
      Echocardiography revealed asymmetric septal hypertrophy in 1988 (interventricular
      septal thickness = 21 mm, posterior wall thickness = 10 mm). Systolic anterior
      motion of the mitral valve was first observed at the end of 1992. The left
      ventricular pressure gradient also gradually increased; it was about 138 mmHg in
      1993 (age 82 yrs). The left ventricular ejection time index increased from 376
      msec in May, 1992 to 459 msec in May, 1994. In September, 1994, the patient's
      condition gradually deteriorated (NYHA IV), and she was admitted to our hospital.
      To attenuate the left ventricular pressure gradient, 150 mg of disopyramide was
      administered. Her condition markedly improved: the left ventricular pressure
      gradient decreased from 180 mmHg to 76 mmHg, and the left ventricular ejection
      time index decreased from 485 msec to 419 msec. These results indicate that a
      left ventricular pressure gradient can be generated rapidly even in a very old
      patient, and that disopyramide may be useful to attenuate the left ventricular
      pressure gradient.

PMID- 8752718
TI  - [Superantigens and immunological diseases].

PMID- 8752719
TI  - [Standard range of peak expiratory flow in normal, healthy Japanese subjects].
AB  - The measurement and analysis of the standard range of peak expiratory flow (PEF)
      in normal, healthy Japanese is necessary at any cost to facilitate bringing the
      Japanese Guidelines for Bronchial Asthma smoothly into effect. In a study as part
      of The Bronchial Asthma Group of the Comprehensive Research Project (Terumasa
      Miyamoto, Chairman of the Planning and Evaluation Committee) under the auspices
      of the Ministry of Health and Welfare, we measured PEF in 2,785 healthy Japanese
      volunteers (1,407 males aged 15-84 years and 1,738 females aged 15-80 years) who
      had no history of smoking, respiratory and/or thoracic diseases, or wheezing with
      four different peak flow meters (e.g., mini-Wright, Assess, Personal Best and
      Vitalograph). As a result of comparing PEF measured by the four meters in the
      same subjects over a short interval of time, we noted significant differences on
      analysis of variance. Accordingly, the equation for prediction should account for
      variables in gender and the type of peak flow meter used. A comparison of cubic
      equations for prediction suggests that the PEF of both Japanese men and women is
      similar to that of the British but is different from that of the Chinese.

PMID- 8752720
TI  - [Trends in the prevalence rate of wheezing in school children].
AB  - Questionnaire surveys of children in all public primary schools in Osaka
      Prefecture have been conducted every other year from 1975 to 1993 (10 times in
      total). The number of schools ranged from 848 to 1,009 and those of the pupils
      from 514,656 to 871,008 (7,128,443 in total responded to each survey). 1. The
      prevalence rate of wheezing was 3.0 +/- 0.1% which was almost constant during the
      period, 1975-1983 and thereafter increased to reach 4.7% in 1993. The rate for
      1st-graders was highest early in the period, but the rate increased with grade
      since about 1985, resulting in a lack of prevalence difference among the 1st to
      5th graders. 2. Their persistent conditions of wheezing were investigated
      according to the individual questionnaires. The increase in the prevalence rate
      from 1985 was found to be caused by the lowering in the remission rate of
      wheezing in addition to the increases in persistent states and new developments
      of the symptoms. 3. Aiming to clarify the correlation between the prevalence rate
      and the air pollution in their places of residence, the prevalence rate was
      compared among various areas. The rates were slightly higher in the business and
      industry area than the residential ones in the suburbs, but increase in the
      prevalence rate from 1985 was commonly found in the respective areas.

PMID- 8752721
TI  - [A statistical investigation of the influence of allergic factors on intractable
      asthma by multiple logistic regression].
AB  - The relationships of the development of intractability in bronchial asthma with
      17 factors, namely 1) sex, 2) age, 3) age of onset, 4) period from onset, 5)
      severity of asthma, 6) type of asthma, 7) family history of asthma within the
      third degree of consanguinity, 8) history of smoking, 9) past history of atopic
      dermatitis, 10) past history of allergic rhinitis, 11) past history of chronic
      sinusitis, 12) past history of nasal polyp, 13) necessity of oral beta-adrenergic
      agonists, 14) necessity of inhaled beta-adrenergic agonists, 15) necessity of
      oral xanthine agents, 16) necessity of inhaled anticholinergic agents and 17)
      necessity of inhaled corticosteroids, were analyzed by multiple logistic
      regression in 160 asthmatic patients. Evaluation of each factor according to the
      relative risk indicated that asthmatic patients tended to become intractable with
      the following categories (relative risk--reference category): more than 40 years
      old (5.2 in the fifth and sixth decades, 4.4 in the seventh and eighth decades-
      the third and fourth decades); the fifth decade or later onset (7.3--the first
      decade); non-atopic type (2.1--atopic type); positive family history of asthma
      (2.8--negative one); an ex- and current smoker (3.1--no smoker); negative past
      histories of atopic dermatitis and allergic rhinitis (4.1 in the former, 2.4 in
      the latter--positive one respectively); positive past histories of chronic
      sinusitis and nasal polyp (5.1 in the former, 6.6 in the latter--negative one
      respectively). Especially, relative risk in asthmatic patients with simultaneous
      positive past histories of chronic sinusitis and nasal polyp was about 16 times
      as high as in ones without both histories. This finding suggested these histories
      strongly participated in the development of intractability in bronchial asthma.

PMID- 8752722
TI  - [Pollen dispersion of Cryptomeria japonica in autumn].
AB  - To clarify the significance of pollen dispersion of Cryptomeria japonica in
      autumn, the distribution pattern of pollen dispersion using specimens collected
      from 1987 to 1995 by Durhum collector was examined. After the dispersion period
      in the spring, the pollen count was suddenly decreased. The total pollen count
      from October to December showed no relation to the total pollen count for that of
      in spring of the same year; but it was closely correlated (r = 0.877) with the
      total pollen count during the dispersion period in the spring of the next year.
      In particular, accurate correlation between the total pollen count during
      November and that in January to May of the following year was observed with the
      correlation index of r = 0.909. Patients with a pollinosis probably for
      Cryptomeria japonica were also observed in the autumn. These results suggest that
      we can forecast the degree of pollen dispersion of Cryptomeria japonica in the
      coming year from the total pollen count during November of the year before.

PMID- 8752723
TI  - Effect of benzodiazepine on antigen-induced eosinophil infiltration into guinea
      pig conjunctiva.
AB  - The effect of benzodiazepine (BZP) on experimental allergic conjunctivitis was
      studied. Male Hartley guinea pigs were sensitized with ovalbumin (OVA) and then
      homologous anti-OVA serum was injected intravenously into guinea pigs for passive
      sensitization. BZP was administered at a dose of 5 mg/kg by intraperitoneal
      injection (i.p.) according to the following schedule respectively; a single,
      repeated twice a day for 3 days, repeated twice a day for 3 days plus a single
      and repeated twice a day for 7 days. OVA challenge was performed to the
      conjunctiva, 20 minutes later, conjunctival edema during the early phase response
      (EPR) was observed and again at 6 hours later, both eosinophil infiltration into
      the conjunctiva and the platelet activating factor (PAF) serum level during the
      late phase response (LPR) were examined. BZP did not inhibit the development of
      conjunctival edema during the EPR. A single dose of BZP did not inhibit, but
      repeated doses of BZP for 3 or 7 days significantly suppressed eosinophil
      infiltration during the LPR. And after repeated doses of BZP for 7 days, all PAF
      serum levels during the LPR were under the lower detection limit of the assay.
      These results suggest that BZP has an inhibitory effect on antigen-induced
      eosinophil infiltration into the conjunctiva during the LPR.

PMID- 8752724
TI  - [Inhibitory effect of a thromboxane A2 receptor antagonist, AA-2414, on active
      oxygen production by alveolar macrophages and polymorphonuclear leukocytes in
      guinea pigs].
AB  - We examined the effect of a thromboxane A2 receptor antagonist, AA-2414, on
      active oxygen production by guinea pig alveolar macrophages and peritoneal
      polymorphonuclear leukocytes and the xanthine-xanthine oxidase (X-XOD) system.
      The production of active oxygen was detected by luminol-dependent
      chemiluminescence (CL). AA-2414 inhibited CL of alveolar macrophages induced by
      zymosan, platelet activating factor (PAF) and phorbol myristate acetate (PMA)
      with IC50 values of 25, 8.8 and 5.6 microMs, respectively. In addition, AA-2414
      reduced CL of polymorphonuclear leukocytes induced by PMA (IC50: 15 microMs). On
      the other hand, AA-2414 had no inhibitory effect on CL in the X-XOD system.
      Superoxide dismutase (SOD) reduced CL in all three of these systems. These
      results suggest that the active oxygen species involved in these systems is
      mainly the superoxide anion (O2-) and that the inhibitory action of AA-2414 on CL
      in guinea pig leukocytes is dependent on inhibiting the production of O2- in
      guinea pig leukocytes.

PMID- 8752725
TI  - [Inhibitory effect of Kanpo-medicines: saiboku-to, syouseryu-to, sairei-to on
      Dermatophagoides farinae antigen-induced IL2 responsiveness in lymphocytes from
      patients with bronchial asthma and their comparison].
AB  - We had previously reported that antigen-induced IL2 responsiveness by lymphocytes
      can be used to identify etiological allergens and to monitor the clinical
      activity in atopic diseases. The effect of Kanpo-Medicines; Saiboku-to, Syoseiryu
      to, Sairei-to, antiallergic agents, on Dermatophagoides farinae (Df) antigen
      induced interleukin 2 (IL2) responsiveness from patients with bronchial asthma
      was studied and compared among 3 Kanpo-medicines. Allergen-sensitized patient
      mononuclear cells pretreated with 30-30,000 ng/ml doses of Saiboku-to for 16
      hours failed to induce responsiveness to IL2 on stimulation with Df antigen in 8
      patients out of 11 (73%). The cells treated with 30 micrograms/ml of Syoseiryu-to
      also failed to introduce the response in 6 out of 10 (60%) with less frequency
      compared with Saiboku-to. Sairei-to also suppressed the response on stimulation
      with a 10 micrograms/ml dose alone in 1 x 10(-3)-1 x 10(-4)ng/ml doses examined
      in 6 patients out of 17 (35%) with much less frequency and % inhibition. Also
      Saiboku-to and Sairei-to not Syoseiryu-to inhibited purified protein derivatives
      (PPD)-induced IL2 responsiveness. However. These agents failed to suppress the
      Con A-induced IL2 responsiveness. Antigen-presenting adherent cells were more
      susceptible to any Kanpo-medicines studied rather than IL2-responding T cells
      except Sairei-to. These results indicated that Kanpo-medicines studied have a
      weak immuno-suppressive property resulting in inhibiting antigen-induced IL2
      responsiveness. Suppressive effects of each Kanpo-medicine seemed to depend on
      combinations and doses of their elements (Syouyaku). Decreased suppressive effect
      of higher doses of any Kanpo-medicine was likely to be mitogenic effects of each
      element on T cells.

PMID- 8752726
TI  - [Immunodiagnosis and blood biochemical diagnosis of visceral candidiasis and the
      cutoff limits of positive].
AB  - Visceral candidiasis is nonspecific in the clinical presentation and a
      microbiological diagnosis is often difficult to make. Currently, several
      techniques are available for detection of the antigen and antibody and/or fungal
      product. We report the results of an investigation in immunodiagnosis and blood
      biochemical diagnosis of visceral candidiasis and suggest the cutoff limits of
      positive, from these findings and those reported by others. The efficiency and
      specificity were 36.4% approximately 60% and 94% approximately 100% for the
      mannan detection kit from Kyokuto Co., Ltd. and 57.1% approximately 100% and 25%
      approximately 69.6% for the CAND-TEC, and 28.6% and 91.7% for PASTOREX CANDIDA.
      For kits using a blood biochemical assay; the efficiency and specificity were 10%
      approximately 56.7% and 91.4% approximately 100% with detection of D-arabinitol
      (cutoff limits; 20 mumol/ml < or =), and 70% approximately 75% and 91.7%
      approximately 100% for Fungal Index (cutoff limits; 60pg/ml < or =). We
      investigated the evaluation of LA test to detect candidal mannan antigen in sera
      obtained from experimental gastric candidiasis of mice with or without treatment.
      There was a good correlation between the change of the titer of mannan antigen
      and the severity of infections, and gastric lesions healed histopathologically 3
      weeks after disappearance of mannan antigen in sera obtained from mice treated
      with an antifungal agent. These findings indicate that the antifungal therapy is
      necessary for more than 3 weeks after the candidal mannan antigen disappeared
      from sera.

PMID- 8752727
TI  - [The antigen (CANDTEC antigen) detected by CAND TEC test for diagnosis of
      candidiasis].
AB  - Most guinea pigs inoculated with 5.4 x 10(9) of C. albicans intraperitoneally,
      produce CANDTEC antigen (GPCANDTECAG) in sera. The antigen is heat-labile (at 56
      degrees C for 30 min) as is that in humans. According to gel filtration, the
      molecule size of the antigen from guinea pigs was 4000KDa or more. ELISA revealed
      the antigen-positive gel fractions to contain a small amount of mannan from the
      yeasts and C3. ELISA using rabbit anti-GPCANDTECAG serum indicated that the two
      CANDTEC antigens from guinea pigs and humans shared determinants. Gel filtration
      indicated that the CANDTEC antigen from patients was from 4000KDa to 3000KDa. In
      the antigen-positive gel fractions, IgM was detected by ELISA, but mannan and C3
      were not detected. However, immunoblotting analysis on the antigen-positive
      fraction revealed a unique band of 200KDa, stained with concanavalin A-ALP. These
      findings indicate that CANDTEC antigens in guinea pigs and humans are immune
      complexes formed after infection of Candida, although the antigens have different
      components.

PMID- 8752728
TI  - [Sero-diagnosis for pulmonary aspergillosis--its utility in early diagnosis].
AB  - The clinical utility of Pastorex Aspergillus, a commercially available
      circulating aspergillus galactomannan antigen detection kit was evaluated. In
      animal models of pulmonary aspergillosis, it was extremely sensitive for
      detection of not only A. fumigatus antigen but also antigens of A. flavus and A.
      niger both in serum and urine. In a preliminary study in autopsied or clinically
      proven cases with aspergillus infections a high positive rate of antigen
      detection was obtained when it was applied prospectively. A total of 1,373
      clinical samples obtained from patients with suspected aspergillus infection were
      examined. Among 67 patients giving antigen-positive results in their clinical
      samples including serum, urine, sputum and others, 17 patients proved to have
      aspergillus infection by histological or cultural studies. Sixteen patients were
      judged to be suspicious of aspergillus infection. Measurement of serum (1 --> 3)
      beta-D glucan by G-test in these cases was well correlated to the results of the
      antigen detection test. However, the serum showed often antigen-negative even
      when it was examined at the peak of illness. The rapid clearance of the antigen
      from circulation was considered to be one of the reasons for this phenomenon. In
      these cases, antigen detection in samples other than serum, such as urine,
      sputum, and pleural fluid was also useful. In conclusion, when using Pastorex
      Aspergillus to obtain the early diagnosis of aspergillus infection frequent
      examination in different types of samples is recommended.

PMID- 8752730
TI  - [Plasma (1-->3)-beta-D-glucan determination for screening deep mycosis].
AB  - Plasma (1-->3)-beta-D-glucan determination has been developed for the diagnosis
      of fungemia and deep mycosis to make up for the low yield of blood culture. This
      method uses Factor G, a coagulation enzyme of the horseshoe crab that is highly
      sensitive to this glucan. Since (1 -->3)-beta-D-glucan is a characteristic fungal
      cell-wall constituent which is common to virtually all fungi, the method aims to
      screen fungal infections as a whole. This is advantageous today when new fungi
      are appearing one after another as a causative agent of opportunistic deep fungal
      infections. Plasma (1-->3)-beta-D-glucan concentrations in 60 normal individuals
      were less than 10pg/ml. With a cutoff value at 20pg/ml, the sensitivity of the
      test was 90%, and the specificity was 100%. No cases of fungal colonization
      showed values above the cutoff level. In addition to invasive candidiasis,
      aspergillosis, and cryptococcosis, trichosporonosis was also found positive with
      the test. Glucanemia was not associated with primary cryptococcosis, probably
      because the growth of the organism is checked by the competent immunity in these
      afebrile patients. Levels of plasma (1-->3)-beta-D-glucan were variable in
      aspergilloma, indicating that the disease is essentially a colonization, but that
      (1-->3)-beta-D-glucan may appear in the blood when cavitary walls are invaded,
      depending on the integrity of local or systemic immunity. In addition to being
      useful for diagnosis, the test is also helpful in initiating early treatment of
      deep mycosis with improved survival.

PMID- 8752729
TI  - [Serological diagnosis for cryptococcosis by the detection of beta-glucan and
      capsular polysaccharide].
AB  - Cryptococcosis is definitely diagnosed microbiologically or pathologically. As
      adjunctive diagnosis, serological and genetic diagnosis could be a promising
      method for rapid diagnosis of cryptococcosis. Capsular polysaccharides such as
      glucuronoxylomannan were used as antigens for serodiagnosis and very high
      sensitivity and specificity were obtained in pulmonar cryptococcosis. Polymerase
      chain reaction for URA5 gene was examined but the sensitivity was not high enough
      for clinical use.

PMID- 8752731
TI  - [Detection of minimal residual leukemia using polymerase chain reaction method].
AB  - Until recently, it was impossible to identify leukemia cells making up less than
      1% of a bone marrow sample, which is designated as minimal residual disease
      (MRD). Owing to the development of the polymerase chain reaction (PCR) MRD can be
      detected at the 10(-5) level by amplifying the leukemia-specific DNA
      rearrangement (BCR/ABL, PML/RARA etc.) or clone-specific DNA sequences (IgH chain
      CDR-III etc.). Here, our studies on MRD of acute lymphoblastic leukemia and acute
      promyelocytic leukemia are presented, and their technical problems and clinical
      significance are discussed.

PMID- 8752732
TI  - [Chromosome analysis and FISH method].
AB  - In hematologic malignancies activation of oncogenes or inactivation of tumor
      suppressor genes are thought to be responsible for its carcinogenesis, just like
      other solid tumors. As these genetic changes are detected as chromosome
      abnormalities, cytogenetic analysis has been used as a tool for diagnosis and
      follow up after therapy. The fluorescence in situ hybridization (FISH) method is
      a new technic which enables us to detect genetic changes both in mitotic and
      interphase cells. It is a useful method in the clinical field which covers the
      disadvantages in cytogenetic analysis, RT-PCR and Southern blotting. We
      practically used the FISH method in diagnosis and follow-up observation of
      minimal residual disease in several kinds of hematologic malignancies. By the
      morphology-FISH method, the relationship between cell morphology and genetic
      changes could be analyzed simultaneously. The FISH method was also applied to
      probe mapping to identify a novel breakpoint cluster region in the 11q23 area in
      adult hematological disease. FISH method is a rapid and powerful tool both in
      clinical and basic study in hematologic disorders.

PMID- 8752733
TI  - [CD45 gating of acute leukemia].
AB  - Flow cytometry is a powerful tool for immunophenotyping of acute leukemia. Gating
      of leukemic cells is currently performed on the two dimensional display of
      forward scatter (FSC) and side scatter (SSC). However, this gating method can not
      discriminate leukemic cells from contaminated normal cells. Therefore, we used a
      CD45 monoclonal antibody to detect leukemic cells (CD45dlm cells) in combination
      with the SSC parameter. This CD45-SSC gating method was very useful for
      immunotyping of AML and ALL, especially leukemia with a low percentage of blasts.
      We recommend this new gating method for more accurate immunophenotyping of acute
      leukemia.

PMID- 8752734
TI  - The results of the "essential laboratory tests" applied to new outpatients--re
      evaluation of diagnostic efficiencies of the test items.
AB  - We have analyzed diagnostic efficiencies of the individual "Essential laboratory
      test" items when these tests were applied to 520 new outpatients in the division
      of comprehensive medicine in a teaching hospital. The integration of these test
      results with history-taking and physical examination resulted in 544 primary
      clinical diagnoses which corresponded to the patient's illness complained and in
      361 additional diagnoses unrelated to their chief complaints but found by chance
      by the addition of the test results. Clinical usefulness of these test items were
      variable depending on the disease category, demonstrating a superior diagnostic
      efficiency in infectious or inflammatory diseases, liver and biliary tract
      diseases, hematological disorders or metabolic diseases such as hyperlipidemia
      and diabetes mellitus, but a lesser degree of usefulness in gastro-intestinal or
      neurogenic diseases. Urine urobilinogen could not establish its clinical
      usefulness because of extremely low diagnostic sensitivity even in liver
      diseases. The leukocyte differential count provided confirmatory information for
      infectious or inflammatory diseases and was helpful for the estimation of the
      etiologic nature of infectious diseases. This study failed to terminate a
      controversy for the adoption of sialic acid instead of erythrocyte sedimentation
      rate (ESR) in the "Essential laboratory test" items, since the former test showed
      lower sensitivity, even though higher specificity, in infectious or inflammatory
      status than ESR. Low albumin globulin ratio (A/G) revealed equivalent diagnostic
      sensitivity and specificity to the elevated levels in alpha 1 and/or alpha 2
      globulin fractions in infectious or inflammatory status, being helpful for the
      evaluation of patient's general condition at a glance. Incidental analysis for
      diagnostic values of cholinesterase and random blood glucose for the detection of
      fatty liver and diabetes mellitus, respectively, suggested that these two tests
      may be included in the "Essential laboratory tests". Simultaneous measurement of
      serum creatinine and blood urea nitrogen levels was recommended for the
      ambulatory screening of renal insufficiency, rather than the measurement either
      alone. The results in this study provide scientific bases on the usefulness of
      the individual test items and should be taken into account in the next version of
      the "Essential laboratory tests".

PMID- 8752735
TI  - [Clinical significance of serum soluble interleukin-2 receptor (sIL-2R)
      determination in patients with rheumatoid arthritis].
AB  - It has been recently shown that soluble interleukin-2 receptor (sIL-2R) is
      related to the pathogenesis of autoimmune diseases. We determined serum levels of
      sIL-2R in patients with rheumatoid arthritis (RA). Fifty-three patients (3 males
      and 50 females from 35 to 70 years old) and sex- and age-matched 50 healthy
      subjects were included in this study. The sIL-2R concentrations positively
      correlated with Lansbury index of RA (r = 0.602, p < 0.01). There was a
      significant correlation between sIL-2R levels and the prevalence of CD3+.HLA-DR+
      lymphocytes (r = 0.420, p < 0.01).

PMID- 8752736
TI  - [Clinical evaluation of hepatitis C virus RNA quantification by competitive
      reverse-transcription PCR].
AB  - We have quantified the hepatitis C virus (HCV) RNA by competitive reverse
      transcription PCR method (Amplicor) HCV quantification monitor kit) in sera with
      positive HCV antibody measured by means of the second generation HCV antibody
      assay. Among the visitors to PL Tokyo Health Control Center for their health
      examination and the patients to National Defense Medical College Hospital, 123
      HCV antibody-positive cases were examined. A positive but low correlation between
      the amount of HCV-RNA and the titer of HCV antibody (r = 0.508, p value < 0.0001)
      was obtained. HCV-RNA was not detectable in 19 HCV antibody-positive cases. Among
      them, 10 cases showed normal ALT values. In the cases with more than 1000
      copies/ml of HCV-RNA, the greater the amount of HCV-RNA the higher ALT values
      were observed, while the titer of HCV antibody was not correlated to ALT. This
      study demonstrated the dissociation and low correlation between HCV-RNA amount
      and antibody-titers in some patients, which may recommend direct quantification
      of RNA for clinical evaluation of the patients with positive-HCV antibody. The
      quantification of HCV-RNA by such rapid and simple methods can be applicable for
      the determination of HCV-RNA amount in routine laboratory works.

PMID- 8752737
TI  - [Mutation detection enhancement (MDE) gel electrophoresis method for analysis of
      the von Willebrand factor gene].
AB  - We conducted electrophoresis using Mutation Detection Enhancement (MDETM) gel (AT
      Biochem) on the von Willebrand factor (vWF) gene from three unrelated patients
      with type 2A von Willebrand disease and one type 3 patient whose point mutations
      we had identified earlier. The mutations were located on the 3'region of exon 28
      in the vWF gene in which three known polymorphisms were included. To eliminate
      any influence of the polymorphisms, 671bp including two AluI sites amplified by
      polymerase chain reaction (PCR) from the region of the vWF gene was digested with
      the restriction enzyme AluI and three fragments (283, 148, and 240bp) were
      obtained. Three polymorphisms were contained in the 283bp fragment and four
      mutations were found in the remaining fragments. Following MDETM gel
      electrophoresis, three of the four cases showed heteroduplex formations. One
      mutation was not detected, although the mutation was found to be heterozygous by
      the restriction analysis of MspI. Failure to detect this mutation may be
      attributed to the fact that it was located on the extreme end of the 148bp
      fragment of the 5' region. The results of this study suggest the MDETM gel
      electrophoresis method is useful in detecting gene mutations or polymorphisms in
      heterozygous subjects. Furthermore, this technique is more convenient than other
      methods for a base mismatch detection since specific apparatus or radioisotopes
      are not required.

PMID- 8752738
TI  - [Responses of cytokines, acute phase proteins, and polymorphonuclear cell
      elastase to surgical stress in the patients with esophageal cancer].
AB  - The serum levels of cytokines (interleukin-1 beta; IL-1 beta, interleukin-6; IL
      6, tumor necrosis factor alpha; TNF alpha), and acute phase proteins (CRP, alpha
      1-antitrypsin; alpha 1-AT, alpha 1-acid glycoprotein; alpha 1-AG, fibrinogen;
      FBG, pancreatic secretory trypsin inhibitor; PSTI), and the plasma concentration
      of polymorphonuclear cell elastase; PMN-E and white blood cell counts were
      measured in 18 patients with esophageal cancer who underwent radical
      esophagectomy through right thoracotomy and reconstruction with gastric tube.
      Peripheral venous blood samples were obtained before and just after operation,
      and on the 1st, 2nd, 3rd, 7th and 14th post-operative day. The serum
      concentrations of IL-6 just after operation were significantly correlated with
      volume of blood loss during operation and duration of thoracotomy. Plasma PMN-E
      levels just after operation seemed to be correlated with those factors, but its
      correlation was not statistically significant. Serum IL-6 levels began to
      increase markedly just after operation, and reached the maximum by the 1st post
      operative day. This elevation preceded that of acute phase proteins, indicating
      that IL-6 may induce the production of acute phase proteins in vivo. Furthermore,
      peak serum values of IL-6 after operation were correlated with volume of blood
      loss and duration of thoracotomy. These results suggest that elevation of IL-6
      and PMN-E levels may reflect the degree of surgical stress, and the measurement
      of IL-6 and PMN-E is useful for the early detection of an inflammatory response.

PMID- 8752739
TI  - [Two cases of lupus nephritis having a high titer of anti-(histone-DNA) complex
      antibody without IgG anti-dsDNA antibody].
AB  - IgG antibody specific to double-stranded DNA (dsDNA) has been recognized as a
      predictive indicator of the renal involvement in systemic lupus erythematosus.
      However, we recently experienced two cases of overt lupus nephritis without IgG
      anti-dsDNA antibody. In both cases, high titers of antibody to the histone dimer
      (H2A-H2B)-dsDNA complex were detected. They responded well to the corticosteroid
      therapy, with a cytotoxic agent in one case, and the titers of anti-(histone-DNA)
      antibody was decreased along with the improvement of proteinuria. Based on the
      recent reports suggesting a pathogenic role of this antibody in lupus nephritis,
      we suggest that measurement of the anti-(histone-DNA) antibody is necessary in
      lupus nephritis patients, especially when IgG anti-dsDNA antibody is not
      detectable.

PMID- 8752740
TI  - [Unusual hepatic fibrosis in three cases of Down syndrome].
AB  - We report three infants with Down syndrome who had hepatic fibrosis, which is
      rare in this syndrome. Liver specimens were obtained by biopsy or autopsy. In one
      patient, the peripheral blood contained blastoid cells, a typical hematological
      feature of the transiently abnormal myelopoiesis of Down syndrome. Ascites and
      hepatosplenomegaly were found in all patients. The intralobular hepatic fibrosis
      was pericellular and perisinusoidal, and the narrowing of the central veins
      resembled that in venoocclusive disease of the liver. We found some
      megakaryocytes in the liver, which were stained for von Willebrand factor and
      platelet glycoprotein IIb/IIIa. In one specimen, collagen type IV and alpha
      smooth muscle actin were stained by immunohistochemical methods, so the fibrosis
      in this case was probably caused by cells such as Ito cells derived from
      myofibroblasts. Overall, the findings suggest that megakaryocytes in the liver of
      these three patients produce collagen-stimulating cytokines such as transforming
      growth factor beta, and that Ito cells were involved in the hepatic fibrosis we
      observed.

PMID- 8752741
TI  - [A case of leiomyomatosis in pelvic lymph nodes].
AB  - We report a rare case of leiomyomatosis in iliac lymph nodes, which was found in
      a woman operated with a diagnosis as keratinizing epidermoid carcinoma of the
      cervix. A 39-year-old Japanese female, married, who had received hormonal therapy
      in her past history, visited the Department of Obstetrics and Gynecology at Kinki
      University Hospital, with a chief complaint of bloody discharge. Colposcopy and
      biopsy suggested a diagnosis of keratinizing epidermoid carcinoma of the cervix.
      A radical hysterectomy and bilateral salpingo-oophorectomy with pelvic lymph
      nodes dissection was performed. Histopathological examination showed a
      keratinizing epidermoid carcinoma of the cervix. An intramural leiomyoma nodule
      (0.5cm in diameter) was detected in the fundus of the uterus.
      Histopathologically, this was a typical benign leiomyoma. The lymph nodes were
      free of neoplasms. But bilateral iliac lymph nodes were enlarged up to soybean
      size. Microscopically, the iliac lymph nodes contained a large amount of well
      differentiated smooth muscle tissue (11/30). Immunohistochemical investigation
      showed a positive reaction for smooth muscle actin and desmins in the spindle
      cells proliferated in the lymph nodes; no cytokeratin positivity was detected.
      Leiomyomatosis of lymph node may rise through metaplasia of intranodal decidua or
      endometriosis by myofibroblasts or smooth muscle cells, reflecting the
      multipotentiality of the pelvic subcoelomic mesenchyme that can be found in the
      peripheral sinus of lymph nodes.

PMID- 8752742
TI  - [Prostate cancer screening in the primary care consultation].

PMID- 8752743
TI  - [The advantages and disadvantages of decentralizing team management].

PMID- 8752744
TI  - [Cardiovascular risk factors in schoolchildren of the city of Cuenca].
AB  - OBJECTIVE: To calculate the levels of different cardiovascular risk factors among
      9 and 10 year old schoolchildren in the city of Cuenca. DESIGN: An observational
      crossover study (cross-sectional). SETTING: The community: three state schools in
      the city of Cuenca. PARTICIPANTS: 156 boys and 151 girls doing 4th and 5th year
      EGB (basic). MEASUREMENTS AND MAIN RESULTS: As well as socio-demographic
      variables, the following anthropometric variables were determined: weight,
      height, body mass index (Khosla-Lowe index), systolic and diastolic blood
      pressure. After collecting samples of venous blood after 12 to 14 hours fasting,
      overall cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were
      determined. The average levels of the lipidic parameters measured in mgrs/dl for
      men and women respectively were 182.4 and 187.2 for overall cholesterol, 110.9
      and 117.0 for LDL-cholesterol, 60.9 and 58.1 for HDL-cholesterol and 53.4 and
      61.3 for triglycerides. These differences were statistically significant in all
      the parameters except overall cholesterol. Neither the pressure levels nor the
      anthropometric variables showed significant differences between genders.
      CONCLUSIONS: The lipid levels found in our study for both for male and female
      schoolchildren display the highest cardiovascular risk levels yet observed in
      Spain. The blood pressure levels are also among the highest published in our
      country.

PMID- 8752745
TI  - [An analysis of long-term computerized prescriptions for those over and under 65
      at a health center].
AB  - OBJECTIVES: To analyse the origin, diagnoses and types of medicine used in
      computerised long-term prescription at our centre, which are classified by age
      distribution; and to extract, if possible, use parameters for monitoring internal
      activities. DESIGN: Descriptive study. SETTING: Zumaia Health Centre (Guipuzcoa).
      PATIENTS: 976 patients divided into those over and those under 65, included in
      the programme of long-term treatment cards. MEASUREMENTS AND MAIN RESULTS: 54% of
      patients were over 65 and 46% under. Average medicines per patient were 3.24 and
      2.23, respectively. 34% of long-term prescription originated in primary care,
      although primary care was only the main indicator to a significant degree in
      group K (CIAP) diagnoses for under-65's. The commonest diagnoses belonged to
      group K, independently of the origin of the prescription. The most prescribed
      medicines were those in groups M and C (IMC), significantly higher in the over
      65's. CONCLUSIONS: Only one third of the prescriptions originated in PC. A
      significant reversal of this tendency was observed in young people with chronic
      group K pathologies. The indication of long-term treatment for psychological
      problems often escapes the public health system; when the PC doctor indicates
      this treatment, he/she usually does so on the basis of symptomatic conditions.
      Monitoring new cases could help us find the efficacy of the corrective measures
      introduced, both at the level of structural innovations and changes in care
      procedure.

PMID- 8752746
TI  - [Drug-to-drug interactions and pharmaceutical advice].
AB  - OBJECTIVE: To describe suspects of drug interactions in primary health care.
      DESIGN: Descriptive and transversal study during 1 month. SETTING: Urban health
      center, primary care, Madrid (Spain). PATIENTS AND OTHER PARTICIPANTS: Patients
      were treated simultaneously with more than 1 drug (145), 2 general practitioners
      (GP) and 1 pharmacist. INTERVENTIONS: GP registered in a sheet-form data from
      diagnostic and pharmacological treatments. The pharmacist checked the sheet-forms
      to detect drug interactions, and later assessed to the GP about it. The proposals
      were classified in 3 ways: no change in treatment; to modify or stop the current
      treatment, and to monitor plasmatic level or clinical parameters. MEASUREMENTS
      AND MAIN RESULTS: 333 drug interactions were detected in 145 patients. The 67.5%
      of interactions produced by 7 groups of drugs: theophylines, diuretics, antacids,
      benzodiacepines, betablockers, NSAID's and ACE's. GP accepted 74% of pharmacist's
      proposals (recommendations). CONCLUSIONS: Seven types of drugs were involved in
      the main interactions in primary care. The drug interactions increased as more
      drugs takes a patient in an accelerated trend. Older than 55 were the most
      affected. GP accepted 3/4 of the recommended pharmacist proposals.

PMID- 8752747
TI  - [The development of a test for evaluating the knowledge of and attitudes on human
      immunodeficiency virus infection in primary health care professionals].
AB  - OBJECTIVE: To compose both a multiple choice test (MCT) to evaluate primary care
      professionals' understanding of HIV infection and a scale to measure their
      attitudes towards it. DESIGN: Validation of questionnaires. SETTING: Ciutat Vella
      health district (City of Barcelona) and university teaching hospitals in
      Barcelona. PARTICIPANTS: 11 residents specialising in contagious disease, 12
      residents from other specialties, 32 general practitioners and 34 nurses from
      primary care, and 64 sixth-year medical students. INTERVENTIONS: A self-filled,
      anonymous questionnaire, completed under supervision. MEASUREMENTS AND MAIN
      RESULTS: All subjects answered a MCT with 21 questions of 4 reply options about
      their understanding of HIV infection, as well as a Likert-type 5-point attitudes
      scale containing 10 items. One question on the MCT was eliminated because of Lack
      of discrimination. The test of understanding gave the PC professionals sufficient
      guarantees of reliability and validity. CONCLUSIONS: A useful questionnaire for
      assessing PC professionals' understanding and attitudes towards HIV infection has
      been gained.

PMID- 8752748
TI  - [The work situation of specialists in family and community medicine educated in
      Asturias].
AB  - OBJECTIVE: To find out the employment situation and the career level of family
      doctors (FD) trained through residency in Asturias. DESIGN: A descriptive
      crossover study carried out with a self-filled questionnaire returned by mail.
      SETTING: All of Spain. PARTICIPANTS: FDs trained through residency in Asturias up
      to 1993. MEASUREMENTS AND MAIN RESULTS: 178 (89%) of the 200 FDs located replied.
      8 who had not finished their course were excluded. Between 1979 and 1983 42
      people began their training (24.7%); 42(24.7%) between 1984 and 1987; and 86
      (50.5%) between 1988 and 1991. 96 worked in health centres (56.4%); 30 in
      hospital casualty (17.6%); 9 in administration and management (5.2%); 16 were
      unemployed (9.4%) and 8 in other posts (4.7%). 49 FD had a permanent post
      (28.8%); 32 of these had started their training before 1984. 63 (37.5%) chose
      family and community medicine (FCM) as a vocation. Of these, 26 began their
      training between 1979 and 1983, 17 between 1984 and 1987 and 20 after 1988. A
      significant relationship was found between starting training in 1984 or before
      and choosing FCM as a vocation; and also between starting FCM training in 1984 or
      before and having a stable job. CONCLUSIONS: The more recent FCM students had
      less vocational motivation for their choice of FCM and greater difficulty in
      obtaining a stable job, which may lead to progressive disenchantment with FCM.

PMID- 8752749
TI  - [The follow-up of a patient cohort with arterial hypertension in primary care].
AB  - OBJECTIVE: To establish effectiveness of the hypertension program basing on the
      detection degree, decreasing of blood pressure and control of hypertension.
      DESIGN: Intervention study. SETTING: Primary care. PATIENTS: A group > or = 14
      years of age, treated by the primary health care and selected at random (3,349).
      Here we found all the patients with hypertension (237). INTERVENTION AND MAIN
      RESULTS: Hypertension program approval of the public health department. Criteria
      followed are those suggested in report V of the Joint National COMMITTEE: Global
      prevalence of hypertension is 7.1% and in the group > or = 65 years of age 51.3%.
      Average decrease of the systolic blood pressure is 18.9 mmHg and that of the
      diastolic blood pressure 13.5 mmHg, both with p < 0.001. Decrease for patients
      with mild hypertension was 5.4-13.8 mmHg for systolic and 6.7-11.8 for diastolic.
      Patients with moderate hypertension 17.3-22.5 and 12.2-15.7 mmHg respectively and
      patients with severe hypertension 27.6-43.0 and 15.0-23.0 mmHg. The 39.7% of
      hypertensive patients have systolic < 140 mmHg and 70.0% have diastolic < 90 mmHg
      at the end of monitoring period. CONCLUSIONS: Actual application of hypertension
      program by our primary care system allows detection of elderly patients with high
      blood pressure, major decrease of blood pressure, together with a greater
      decrease even whether they high at the beginning of the monitoring.

PMID- 8752750
TI  - [The Methadone Maintenance Program for intravenous heroin addicts. What
      information do primary care physicians have?].
AB  - OBJECTIVES: To find the profile of the heroin addict included in the Methadone
      Maintenance Programme (MMP) and the standard of information which primary care
      doctors have about these patients. DESIGN: A descriptive crossover study.
      PATIENTS AND OTHER PARTICIPANTS: All the drug addicts included in the MMP,
      located at the Drug Dependency Care Centre (DDCC) of the Segovia Red Cross (53
      patients) and their respective local doctors (22 doctors). INTERVENTIONS:
      Reviewing medical records in the DDCC archives and a closed questionnaire
      submitted to the local doctors. MEASUREMENTS AND MAIN RESULTS: The patients
      included in the MMP were, on average: male, aged 28,4 ( +/- 5,4 years), single,
      urban dwellers, unemployed, polydependent, with average time taking heroin 8.4
      years ( +/- 4,5) and with family history of drug-taking in 47,1% of cases. The
      reason for demanding the MMP was legal problems in 41.5% of cases. 9.4% were
      referred to the DDCC by health clinics. 15,7% of local doctors referred their
      drug addicts to the DDCC. 89,5% of local doctors never received medical
      information from the DDCC. CONCLUSIONS: Legal problems were more important
      motives than health for requesting inclusion in the MMP. The poor coordination
      between primary care and the DDCC is notorious, which suggests we should try to
      establish greater collaboration between the two areas to tackle this problem.

PMID- 8752751
TI  - [A brief review of the debate over social inequalities in health].

PMID- 8752753
TI  - [The opinions of family medicine residents in Andalucia on some aspects related
      to their specialty].

PMID- 8752752
TI  - [The approach to generalized pruritus in primary care].

PMID- 8752754
TI  - [Immunity to rubella in pregnant women in the health area of Toledo].

PMID- 8752755
TI  - [The incomprehensible decisions of scientific committees].

PMID- 8752756
TI  - [Detection of K-ras point mutations in the stool of patients with colorectal
      tumors].
AB  - Using mutant-allele-specific amplification procedure, patients with colorectal
      tumors were analyzed for K-ras point mutations in the stool and the tumor tissue.
      K-ras mutation of DNA purified from the stool was detected in 10 of 40 (25.0%)
      cancer patients, and in 3 of 10 (30.0%) adenoma patients. Otherwise, in the cases
      whose tumors contained the mutations, it was detected with the frequency of 71.4%
      in cancers, and 100% in adenomas. This frequency tended to decrease in the
      cancers of distal colon or small size, but there was no significant. This study
      suggested that stool analysis of genetic alterations would develop diagnostic
      method for colorectal cancer.

PMID- 8752757
TI  - [Percutaneous microwave coagulation therapy for hepatocellular carcinoma--study
      on its therapeutic effect in surgical cases].
AB  - Six patients with hepatocellular carcinoma were subjected to percutaneous
      microwave coagulation therapy (PMCT) by ultrasonic guiding. The size of the main
      tumor in the present cases was limited to not more than 2 cm. From 18 to 48 days
      after PMCT, each patient was subjected to surgery and pathological examination.
      By macroscopic observation, the PMCT area including both non-tumor and tumor
      regions looked yellowish white, and the boundary was clearly recognized. In the
      histological examination, the coagulation area surrounded by fibrous capsule was
      found, and deletion of nuclei and changes in stainability were observed in the
      marginal region. These changes indicated obvious coagulation necrosis, but the
      changes became less intense toward the center in the area, and in some portions,
      the tissue was indistinguishable from viable cells by light microscopy. In 2
      cases out of the 6, part of the tumor remained outside the coagulation area.
      Since only the area determined by the microwave electrode is coagulated to cause
      necrosis on PMCT, sufficient safety margin should be required.

PMID- 8752758
TI  - [Hepatocellular carcinoma following interferon therapy].
AB  - We experienced six patients with resected hepatocellular carcinoma (HCC)
      following interferon (IFN) therapy. Hepatitis virus C-RNA in polymerase chain
      reaction was positive in all patients prior to the IFN therapy. HCV-RNA became
      negative in two patients following IFN therapy, and was re-positive at the time
      of detection of HCC. In histological studies prior to the IFN therapy, pre
      cirrhosis was diagnosed in four out of six patients and chronic active hepatitis
      2B (CAH2B) in one according to the Europian classification. In non-cancerous
      portion of the liver, cirrhosis developed in five patients, and CAH2B in one.
      There was no significant correlation among the interval of HCC detection
      following IFN therapy, tumor size, tumor location, and histological findings.
      Patients should be carefully followed up by serum alpha fetoprotein levels or
      ultrasonography of the liver during and following IFN therapy.

PMID- 8752759
TI  - [The influence of endoscopic injection sclerotherapy (EIS) on respiro-circulatory
      condition in patients with portal hypertension--the effect of oxygen
      administration].
AB  - We studied the influence of EIS on the respiro-circulatory condition of patients
      with portal hypertension. Subjects were fifty patients with portal hypertension
      who were successfully injected more than 5.0 ml of sclerotant into varices. A
      prospective randomized controlled trial was proposed to elucidate the effect of
      prophylactic administration of pure oxygen. Twenty-five patients inhaled pure
      oxygen (O2), remaining twenty-five patients did not during EIS. Respiro
      circulatory function of patients was evaluated by monitoring O2 saturation, pulse
      rate and blood pressure during EIS. PaO2 was measured before and after EIS in
      seven patients without O2. EIS by the 5% ethanolamine oleate with iopamidol (EOI)
      was performed under X-ray monitoring. O2 saturation in patients without O2
      inhalation was lowered, whereas that in patients with O2 inhalation was stable
      during EIS. O2 saturation during injection of EOI and after EIS in patients
      without O2 inhalation was significantly lower than that in patients with O2
      inhalation. Pulse rate was significantly lower and a rise in blood pressure was
      smaller in patients given O2. No significant differences of PaO2 was noted before
      and after EIS. In conclusion, the monitoring of O2 saturation, pulse rate and
      blood pressure is necessary during EIS. Prophylactic administration of pure
      oxygen may be useful for prevention of hypoxic state and respiro-circulatory
      stabilization during EIS.

PMID- 8752761
TI  - [A case of ulcerative colitis associated with common variable immunodeficiency].

PMID- 8752760
TI  - [A case of gastric carcinoid tumor associated with type A gastritis treated with
      distal gastrectomy].

PMID- 8752762
TI  - [Combined hepatocellular and cholangiocellular carcinoma: a case report with
      invasion to the left hepatic duct of hepatocellular carcinoma].

PMID- 8752763
TI  - [Drug-induced purpura in a patient with chronic hepatitis C due to interferon
      therapy].

PMID- 8752764
TI  - [A case of primary sclerosing cholangitis associated with Sjogren's syndrome and
      chronic pancreatitis].

PMID- 8752765
TI  - [A case of biloma treated with a expandable metallic stent].

PMID- 8752766
TI  - [A case report: resection of the uncinate process of the pancreas for ultra-small
      pancreatic mucin-producing carcinoma of the branch type].

PMID- 8752767
TI  - [Anesthesia mechanisms: nerve excitation and temperature].
AB  - Depolarization of a nerve membrane produces heat while repolarization absorbs
      heat. This is equivalent to the phase transition of water where freezing of water
      produces heat and melting of ice absorbs heat. In this context, high temperature
      (as in water) supports resting potential and low temperature (as in ice) supports
      action potential. When assessed by the equilibrium between the two phases,
      anesthetized state is the high temperature state. Nevertheless, low temperature
      supports anesthesia. The two opposing facts confuse the understanding of
      anesthesia mechanisms. The inconsistency arises from the two effects of heat on
      nerve excitation. One is one the equilibrium between the resting and active
      states of the excitation machinery, and the other is on the reaction rate
      process. This review annotLatsz why low temperature facilitates anesthesia while
      high temperature supports the resting state of nerves.

PMID- 8752768
TI  - [Assessment of cardiac functions in patients for coronary artery bypass graft
      using transesophageal echocardiography before and after cardiopulmonary bypass].
AB  - We evaluated cardiac functions in 7 patients for elective coronary artery bypass
      graft surgery before and after cardiopulmonary bypass (CPB) using transesophageal
      echocardiography (TEE). There was no significant difference in the ratio of end
      systolic meridional wall stress (ESS) and end-systolic area (ESA), which is a
      good indicator of cardiac contractility, before and after CPB period. However,
      left ventricular stroke work index (LVSWI) decreased after CPB compared to that
      before CPB. There was a positive correlation between the ESS/ESA ratio after
      induction of anesthesia and left ventricular ejection fraction at the pre
      operative study. As the ESS/ESA ratio represents cardiac contractility and the
      ESS is a reliable indicator of afterload, we thought it possible to assess
      cardiac contractility and precise afterload by using TEE during perioperative
      period.

PMID- 8752769
TI  - [Distribution of irrigating fluid to intracellular and extracellular fluid space
      during transurethral prostatectomy I--Estimation of irrigating fluid absorbed by
      measuring serum osmolality].
AB  - Twenty-three patients undergoing transurethral resection of the prostate (TURP)
      under spinal anesthesia were studied. The irrigating fluid widely used in Japan
      is a hypo-osmolar solution with 3% sorbitol (Uromatic S, 170 mOsm.kgH2O-1,
      Baxter). The blood loss and the distribution of the irrigating fluid absorbed
      were computed from serum osmolality, blood urea nitrogen, and hematocrit using
      the equation we had formulated. The blood loss, the total fluid absorbed (ABS),
      and the volumes distributed to intracellular space (delta ICF) and extracellular
      space (delta ECF) were 419 +/- 677 ml, 1,582 +/- 1,446 ml, 384 +/- 348 ml and 778
      +/- 1,279 ml (mean+/-SD), respectively. The correlation coefficient of delta OSM
      (difference between pre- and post-surgical serum osmolality) vs ABS and that of
      delta OSM vs delta ICF were high (0.98, 0.98) but that of delta Na (difference
      between pre- and postsurgical serum sodium) vs ABS was low (0.56). The linear
      regression equations of ABS vs delta OSM and delta ICF vs delta OSM were ABS (L)
      = 0.362 x delta OSM and delta ICF (L) = 0.088 x delta OSM, respectively. These
      equations means that one mOsm.kgH2O-1 reduction of the serum osmolality is the
      result of 362 ml of irrigating fluid absorbed, 88 ml of which shifting into the
      intracellular space.

PMID- 8752770
TI  - [Analgesic mechanism of ketamine].
AB  - The present study was conducted to investigate the mechanism of antinociceptive
      action of ketamine in rats. Intraperitoneally administered ketamine showed
      antinociception in the tail flick (TF) and mechanical paw pressure (MPP) tests in
      a time- and dose-dependent manner. However, intrathecal ketamine, 50-1,000
      micrograms, did not exert any antinociceptive effect in TF and MPP tests. In
      contrast to the antinociceptive actions of intraperitoneal ketamine in TF test in
      intact rats, ketamine did not produce any effect in spinally transected rats.
      Further, pretreatment with an intrathecal serotonin antagonist, methysergide, and
      an intrathecal alpha 2 adrenergic antagonist, yohimbine, abolished the
      antinociceptive effects of intraperitoneal ketamine in the TF and the MPP tests.
      The monoamine levels (noradrenaline, MHPG, 5-HT, 5-HIAA) in the spinal cord,
      which were measured by high performance liquid chromatography, increased after
      the intraperitoneal administration of ketamine. We conclude that the
      antinociceptive effects of ketamine involve an activation of the monoaminergic
      (noradrenergic and serotonergic) descending inhibitory system, and that spinal
      ketamine does not affect the responses to the acute noxious stimuli.

PMID- 8752771
TI  - [The effect of droperidol and sevoflurane on serotonin-induced
      bronchoconstriction in dog].
AB  - Serotonin is a potent bronchoconstrictor, but the site of bronchoconstriction has
      not been determined. The present study was performed in dogs to clarify the site
      of bronchoconstriction induced by serotonin as well as to clarify the
      bronchodilating effect of droperidol and sevoflurance on the serotonin-induced
      bronchoconstriction by means of deflation flow-volume curve (DFVC) method,
      passive expiratory flow volume curve (PEFVC) method and respiratory system
      impedance measurement by forced oscillation method. Infusion of serotonin (60
      micrograms.kg-1.min-1) induced a significant decrease in maximal expiratory flow
      at 10% of maximal expiratory volume (DEF10) by DFVC method and a significant
      increase in respiratory system impedance (Z). After droperidol (0.1 mg.kg-1)
      injection, DEF10 and Z returned to the control level and they remained unchanged
      even after the termination of serotonin infusion. Respiratory system compliance
      and resistance by PEFVC were unchanged by both serotonin and droperidol infusion
      or sevoflurane. Inhalation of 5% sevoflurane during serotonin infusion caused no
      significant change in DEF10. These findings indicate that serotonin-induced
      bronchoconstriction involves the small airway as well as the large airway. It is
      suggested that droperidol reversed serotonin-induced small airway constriction
      probably due to the antagonism of serotonin receptor in the airway.
      Bronchodilating effect of sevoflurane is probably limited in the small airway
      constricted by serotonin.

PMID- 8752772
TI  - [Relationship among the heart, vasculature and blood volume at perioperative
      period: the influence of volatile anesthetics].
AB  - Ventricular pressure-volume relationship enables us to understand the
      relationship among the heart, vasculature, and blood volume, since it provides,
      on a single plane, the preload, afterload, and cardiac contractility, which are
      major determinants of stroke volume. In addition, it is also possible to estimate
      cardio-vascular matching, namely the optimum of cardio-vascular interaction, by
      an analysis of ventricular pressure-volume relationship. Volatile anesthetics
      cause circulatory depression due primarily to decreases in cardiac contractility
      and stressed blood volume. The optimal treatment for it is to restore these
      decreases produced by volatile anesthetics. Thus, an increase in afterload by
      vasoactive agents may cause deterioration of cardio-vascular matching. A
      rationale for optimal perioperative circulatory management can be deduced from
      understanding a quantitative interaction among the heart, vasculature, and blood
      volume.

PMID- 8752773
TI  - [Transesophageal echocardiography (Part 1): Basic concepts in two-dimensional
      imaging and M-mode].
AB  - Transesophageal echocardiography has features suitable for intraoperative use. It
      enables intraoperative evaluation of cardiac or thoracic aortic lesions before
      and after surgical intervention. It also provides real-time information on
      cardiac performance throughout the operation without interfering with surgical
      procedures. Anatomical relationship of the esophagus and the heart allows the use
      of high frequency ultrasound, which is advantageous to increase the resolution of
      echo images. An ultrasound beam emitted by a transducer is absorbed, reflected
      and scattered as it progresses in inhomogeneous living tissues. The reflected
      ultrasound waves reach the transducer, and their mechanical vibrations are
      converted to electronic signals. These signals are further processed by the
      ultrasound imaging system, and echo images are displayed on a video screen.
      Ultrasound imaging techniques include M-mode, two-dimensional imaging and Doppler
      techniques. M-mode is the most basic technique, which displays a scroll of the
      echo signals along a single ultrasound beam on a video screen. It has higher
      temporal resolution than other modes, and is therefore useful for precise timing
      of events and quantitative measurements of size or distance within the cardiac
      cycle. Two-dimensional mode produces a real-time cross-sectional view of cardiac
      structures, which can be easily interpreted. It is suited to visualization of
      anatomic structures.

PMID- 8752775
TI  - [Changes of respiratory system compliance by closure of congenital abdominal wall
      defects and postoperative complications].
AB  - We treated four neonates with congenital abdominal wall defects and performed
      pulmonary function testing before and after closure of abdominal wall defects.
      Pulmonary mechanics were measured by passive occlusion technique. Static
      respiratory system compliance (Crs) was 0.61 +/- 0.16 ml.cmH2O-1 .kg-1 (mean +/-
      SD) preoperatively and decreased to 0.31 +/- 0.03 ml.cmH2O-1.kg-1
      postoperatively. Two cases with a marked decrease in Crs after the abdominal wall
      closure seemed to have longer intubation time and N.P.O period and to have more
      complications than with the other two cases. Our experience provides an evidence
      that Crs measurement could be a useful index in decision-making of the treatment
      of neonates with congenital abdominal wall defects.

PMID- 8752774
TI  - [Acute brain expansion during emergency neck clipping surgery for cerebral
      aneurysms in a patient with dilated cardiomyopathy].
AB  - A 61-year-old male with coma and undiagnosed dilated cardiomyopathy received
      emergency cerebral aneurysm surgery. Anesthesia was induced with thiamylal,
      fentanyl and vecuronium and maintained with 66% N2O and 1.0% isoflurane. Five
      hundred ml of 20% mannitol was infused in 30 min. At the end of the infusion,
      hypotension occurred. Immediately after the injection of ephedrine, acute brain
      swelling was observed. The operation was switched to external decompression. Post
      operative echocardiography revealed the presence of dilated cardiomyopathy (DCM).
      The ejection fraction was 34%. Two weeks later, the second operation was
      scheduled. The anesthesia was induced with fentanyl, midazolam and vecuronium and
      maintained with N2O and 0.7% isoflurane. Nitroglycerine, lidocaine, PGE1,
      dopamine and dobutamine were infused throughout the operation. Five hundred ml of
      20% mannitol was infused in 60 min. There were no considerable hemodynamic
      changes and no episode of brain expansion during operation. We conclude that the
      rapid infusion of mannitol can trigger acute cardiac failure and brain edema in
      patients with DCM.

PMID- 8752776
TI  - [The effect of continuous epidural infusion of combination of buprenorphine and
      bupivacaine for postoperative pain relief using a portable 0.5 ml.h-1 type
      infuser with patient control module].
AB  - Using a portable 0.5 ml.h-1 type infuser with Patient Control Module (Baxter
      infuser BB+ PCM), we compared patients receiving continuous epidural infusion
      with patients using self controlled analgesia system for postoperative analgesia
      after upper abdominal surgery. Twenty-one patients were randomized into three
      groups: group I (n = 7) received 20 micrograms.h-1 of buprenorphine (Bu) with
      additional 20 micrograms of Bu; group II (n = 7) 20 micrograms.h-1 of Bu plus 1
      mg.h-1 of bupivacaine (Bup) with additional 20 micrograms of Bu plus 1 mg of Bup;
      group III (n = 7) 20 micrograms.h-1 of Bu plus 2 mg.h-1 of Bup with additional 20
      micrograms of Bu plus 2 mg of Bup. In all three groups, patients received
      supplemental Bu 0.1 mg intramuscularly as needed. During 48-hours
      postoperatively, we evaluated verbal descriptor pain scale, sedative scale,
      visual analogue scale, supplemental doses of Bu, and side effects. Total doses of
      Bu during the first 12 hours were significantly larger than those during other 12
      hour period in all the groups (P < 0.05). In each period during the 12 to 48
      hours after operation, the percentage of the patients who needed no supplemental
      Bu was 71.4-100%, which is higher than during the 0 to 12-hours (47.7%). There
      was no significant difference in verbal descriptor pain scale, sedative scale,
      visual analogue scale, and the incidence of side-effect among the three groups.
      Continuous epidural infusion with Bu using a portable 0.5 ml.h-1 type infuser
      with patient control module was effective for alleviating postoperative pain
      except in the first 12-hour period. However, addition of Bup to Bu did not
      improve the quality of postoperative epidural analgesia.

PMID- 8752777
TI  - [Anesthetic management of 6 cases with dilated cardiomyopathy for non-cardiac
      surgery].
AB  - We report anesthetic management of 6 cases (5 patients) with dilated
      cardiomyopathy for noncardiac surgery. The severity of their cardiomyopathy
      evaluated by left ventricular ejection fraction (LVEF) utilizing echocardiography
      was different in each case. The management of anesthesia was divided into 3 steps
      according to the LVEF. In cases with LVEF over 0.45, it was possible to perform
      regular anesthetic management by carefully selecting and controlling anesthetic
      agents. In 2 cases with LVEF from 0.2 to 0.4, anesthetic management was
      difficult. Some vasoactive drugs (e.g. dopamine) and intensive monitoring devices
      (e.g. pulmonary artery catheter) were needed to optimize anesthetic course. In
      one case with LVEF less than 0.2, we discussed much about surgical indication.
      Because of the malignant nature of the tumor, we agreed to proceed. IABP was
      inserted preoperatively and this proved to be life-saving during the procedure.
      It is important to have an inter-departmental discussion on these severely
      compromised cases.

PMID- 8752778
TI  - [An elderly patient with traumatic acute subdural hematoma who "talked and
      deteriorated"].
AB  - A 62-year-old man was transferred to our hospital 20 min after a motor vehicle
      accident. The CT scan on admission revealed mixed density area of acute subdural
      hematoma, but he was asymptomatic on physical examination. Course observation
      without brain edema therapy resulted in severe disturbance of consciousness 2
      hours after the traffic accident. The CT scan at this time showed the enlargement
      of the hematoma, and midline shift. Emergent external decompression was performed
      4 hours after the head trauma, but he died of heart failure on the 8 th day after
      the operation. We consider that the important factors for saving this patient
      were rapid diagnosis by repeated CT scan and conservative brain edema therapy
      early in the post-traumatic period.

PMID- 8752779
TI  - [Pre-emptive analgesia from intravenous administration of opioid: no effect with
      pentazocine].
AB  - The influence of timing of administration of preoperative pentazocine on pain and
      analgesic requirements after surgery was studied in 46 patients undergoing total
      abdominal hysterectomy. Twenty-three patients received thiamylal 5 mg.kg-1 on
      induction of anesthesia, followed by pentazocine 30 mg or 60 mg before surgical
      incision (group A). Twenty-three control patients received pentazocine 30 mg or
      60 mg, 5 min after abdominal incision (group B). The visual analogue scales for
      pain 24 h after operation were 6.0 cm at 30 mg dose in group A or 5.3 cm at 60 mg
      dose in group A and 5.7 cm at 30 mg dose in group B or 4.7 cm at 60 mg dose in
      group B. There were no differences in the visual analogues scales. Pentazocine
      consumption in the first 24 h after surgery was 67.5 mg at 30 mg dose in group A
      or 52.5 mg at 60 mg dose in group A and 70.9 mg at 30 mg dose in group B or 51.8
      mg at 60 mg dose in group B. We conclude that postoperative pentazocine
      consumption and pain scores are no different when pentazocine is given before or
      after skin incision for abdominal hysterectomy and that there is no clinically
      useful pre-emptive analgesic effect with these doses of pentazocine.

PMID- 8752780
TI  - [A reused suction catheter was broken and produced a tracheobronchial foreign
      body].
AB  - We present a rare case involving a broken suction catheter that became lodged in
      the tracheobronchial tree. An eight-month-old infant was scheduled for
      hernioplasty. Following intubation with a 4 French (Fr.) endotracheal tube, a 5
      Fr. reused suction catheter was applied for suctioning a moderate amount of
      secretion. This catheter had been resterilized by ethylene oxide gas (EOG).
      Insertion of the catheter into the tube was not done smoothly, and we could not
      obtain any secretion. During the extraction of the suction catheter by force, the
      catheter broke. The distal fragment (20 cm length) seemed to have been lodged in
      the tracheobronchial tree. Prior to its removal by bronchoscopy, the endotracheal
      tube was extubated. Fortunately the remaining part of the catheter come out with
      the tube. Ten cm of the fractured catheter was included in the tube and 5 cm
      protruded from the tube. The catheter of smaller diameter is easy to be broken
      even by weaker force. After resterilization by EOG for once, there was no change
      in length and force at breaking point. Elongation of the broken catheter (85.5%)
      was less compared with the new sample (155%). At the breaking point, half of the
      cross section was very smooth and looked as if it had been cut by a razor, while
      the other half appeared to have been broken by pulling. The break may have
      started from the crack which had occurred at the insertion or resterilization.
      Therefore, we should restrict the reuse of small suction catheters, and should
      always utilize the catheter of the largest size possible.

PMID- 8752781
TI  - [Intraoperative TEE revealed the mitral valve vegetation and the operation was
      cancelled].
AB  - Intraoperative transesophageal echocardiography (TEE) was performed on a 53-yr
      old man scheduled for the venous graft in the left leg under general anesthesia.
      The TEE revealed the severe mitral valve vegetation and because of the finding,
      the operation was cancelled. Preoperative transthoracic echocardiography showed
      mitral valve regurgitation only, and not mitral valve vegetation. TEE was useful
      not only in assessing global and regional cardiac function, but also in
      visualizing anatomic abnormalities of the heart and their influence on cardiac
      performance.

PMID- 8752782
TI  - [A new colorimetric CO2 indicator Colibri].
AB  - A new colorimetric carbon dioxide (CO2) indicator Colibri is a disposable,
      compact and light weighted device. Colibri does not need to be calibrated and is
      easily usable in an emergency. It indicates blue with CO2 below 4 mmHg and
      becomes yellow with CO2 above 40 mmHg. In comparison with EASY CAP, Colibri
      functions for a longer period and it has a humidifier and a bacterial filter.
      Colibri is useful for emergency situations and anesthetic care.

PMID- 8752783
TI  - [Evaluation of the training of the anesthesiologist].
AB  - In order to evaluate both the knowledge and the degree of competence acquired by
      anesthesiology trainees, we constructed a checklist and began using it in January
      1994. Twenty-one trainees participated in a 3-month program ending in February
      1995. By means of the checklist, we attempted to evaluate the extent of their
      individual attainment. The total number of anesthesia administered was 50.9 +/-
      7.8 cases. The total anesthesia time was 212.0 +/- 32.8 hours, and 76.2 % of the
      anesthesia methods applied involved either nitrous oxide-sevoflurane or nitrous
      oxide-isoflurane. Using a 5-level rating scale, the self-assessment by the
      supervising doctor tended to be one point higher than the assessment by the
      trainees. We plan to improve this checklist to improve the results of training.

PMID- 8752785
TI  - [A report on the present status of education in cardiopulmonary resuscitation].

PMID- 8752784
TI  - [Experience of Anesthesia in northern Iraq after the Gulf War].
AB  - After the Gulf war, I had a chance to train young local doctors in northern Iraq
      for two years. There were many problems in practicing anesthesia; lack of
      medicine, lack of oxygen supply, haphazard power failure, no monitors functioning
      during operation. The facility for anesthesia is not enough for the training of
      these young anesthetists. Therefore, the further training in a well equipped
      hospital in another country is mandatory for them. Unfortunately there is no such
      training programme for them at the moment. Japanese medical society should
      implement a training program in Japan, in order to provide the full training
      course for overseas doctors to get a consultant degree.

PMID- 8752786
TI  - Angioscopic evaluation of atherosclerotic plaques: validation by histomorphologic
      analysis and association with stable and unstable coronary syndromes.
AB  - OBJECTIVES: We validated coronary angioscopic observations with histologic
      assessment of material removed by atherectomy. BACKGROUND: Up to now, angioscopic
      findings have been primarily descriptive, and the clinical significance still
      needs to be substantiated. The proposed Ermenoville classification is relevant
      but has not yet been validated by histomorphologic analysis. METHODS: We compared
      angioscopic findings in patients with different coronary syndromes and used
      atherosclerotic material retrieved by directional coronary atherectomy to
      validate the angioscopic observations. Coronary angioscopy was performed in 63
      patients (56 men, 7 women) with stable (26 patients) and unstable angina (37
      patients) before and after directional coronary atherectomy. The identity of
      atherectomized material was confirmed by ex vivo visualization with the
      angioscope and by postatherectomy angioscopy. Angioscopic and histologic findings
      could be compared in 44 of 63 patients. RESULTS: Angioscopic findings were
      grouped into gray-white and yellow lesions (gray-yellow, deep yellow, yellow-red
      or yellow-pink). We found that patients with unstable angina had predominantly
      yellow lesions (89%). In patients with stable angina, gray-white (43%) or yellow
      (57%) lesions were similarly distributed. Ruptured yellow plaques and red or pink
      thrombi were identified in 11% of patients with stable angina and 39% of patients
      with unstable or early postmyocardial infarction angina. Histologically, gray
      white lesions represented fibrous plaque without degeneration in 64% and with
      degeneration in 36% of patients. Gray-yellow lesions were associated
      predominantly with degenerated plaque (64%) and, to a lesser extent, with fibrous
      plaque (14%) or atheroma (14%). Deep yellow and yellow-red lesions represented
      either atheroma (53%) or degenerated plaque (42%). CONCLUSIONS: Our study
      establishes a histomorphologic basis for classification and interpretation of
      angioscopic findings. Yellow plaque color is closely related to degenerated
      plaque or atheroma and is associated with unstable coronary syndromes.

PMID- 8752787
TI  - Calcium antagonists and mortality in patients with coronary artery disease: a
      cohort study of 11,575 patients.
AB  - OBJECTIVES: This study sought to establish the risk ratio for mortality
      associated with calcium antagonists in a large population of patients with
      chronic coronary artery disease. BACKGROUND: Recent reports have suggested that
      the use of short-acting nifedipine may cause an increase in overall mortality in
      patients with coronary artery disease and that a similar effect may be produced
      by other calcium antagonists, in particular those of the dihydropyridine type.
      METHODS: Mortality data were obtained for 11,575 patients screened for the
      Bezafibrate Infarction Prevention study (5,843 with and 5,732 without calcium
      antagonists) after a mean follow-up period of 3.2 years. RESULTS: There were 495
      deaths (8.5%) in the calcium antagonist group compared with 410 in the control
      group (7.2%). The age-adjusted risk ratio for mortality was 1.08 (95% confidence
      interval [CI] 0.95 to 1.24). After adjustment for the differences between the
      groups in age and gender and the prevalence of previous myocardial infarction,
      angina pectoris, hypertension, New York Heart Association functional class,
      peripheral vascular disease, chronic obstructive pulmonary disease, diabetes and
      current smoking, the adjusted risk ratio declined to 0.97 (95% CI 0.84 to 1.11).
      After further adjustment for concomitant medication, the risk ratio was estimated
      at 0.94 (95% CI 0.82 to 1.08). CONCLUSIONS: The current analysis does not support
      the claim that calcium antagonist therapy in patients with chronic coronary
      artery disease, whether myocardial infarction survivors or others harbors an
      increased risk of mortality.

PMID- 8752788
TI  - Whatever happened to the calcium antagonist controversy?

PMID- 8752789
TI  - Plasma immunoreactive endothelin concentration correlates with severity of
      coronary artery disease in patients with stable angina pectoris and normal
      ventricular function.
AB  - OBJECTIVES: The present study tested the hypothesis that plasma immunoreactive
      endothelin concentration correlates with the severity and extent of coronary
      atherosclerosis. BACKGROUND: Plasma endothelin-1 concentration is increased in
      patients with unstable coronary syndromes and advanced atherosclerosis. This
      finding, together with other clinicopathologic observations, suggests that
      endothelins may participate in the atherogenic process. However, the relation
      between plasma immunoreactive endothelin and coronary artery disease in patients
      with stable angina pectoris remains controversial. METHODS: Ninety consecutive
      patients undergoing coronary angiography for the investigation of exertional
      chest pain and 49 normal control subjects were prospectively studied. Eleven
      patients had normal coronary angiographic findings (group I), 65 had coronary
      artery stenoses (group II), and 14 had coronary artery disease plus symptoms
      indicating atheroma in other vascular territories (group III). Computerized
      angiography was used to determine the extent, severity and morphology of coronary
      stenoses. Plasma immunoreactive endothelin was measured by radioimmunoassay.
      RESULTS: Mean (+/- SD) plasma endothelin concentration (pg/ml) was significantly
      higher in patients than in control subjects (7.29 +/- 4.07 vs. 3.48 +/- 1.29, p <
      0.0001). Endothelin levels were higher in patients of group III than in those of
      groups II and I (9.43 +/- 5.48, 7.20 +/- 3.72 and 4.94 +/- 2.89, respectively, p
      = 0.02). In patients of group II, plasma endothelin correlated with the maximal
      degree of stenosis in each patient (r = 0.25, p = 0.04) and with the number of
      stenoses with > or = 70% diameter narrowing (r = 0.36, p = 0.002). The highest
      plasma endothelin levels were found in patients with total occlusions (8.65 +/-
      3.78 vs. 6.46 +/- 3.51 p = 0.02). CONCLUSIONS: Plasma immunoreactive endothelin
      concentration is increased in patients with chronic stable angina. The higher
      levels occur in patients with severe stenoses and total coronary occlusion.

PMID- 8752790
TI  - Prognostic significance of transient ischemic episodes: response to treatment
      shows improved prognosis. Results of the Total Ischemic Burden Bisoprolol Study
      (TIBBs) follow-up.
AB  - OBJECTIVES: The Total Ischemic Burden Bisoprolol Study (TIBBS) follow-up examined
      cardiac event rates in relation to transient ischemia and its treatment.
      BACKGROUND: It is unclear whether transient ischemia on the ambulatory
      electrocardiogram has prognostic implications in stable angina and whether
      medical treatment can improve the prognosis. METHODS: The TIBBS trial was an 8
      week, randomized, controlled comparison of the effects of bisoprolol and
      nifedipine on transient ischemic episodes in patients with stable angina
      pectoris. Of the 545 patients screened, 520 (95.4%) could be followed up. Rates
      of cardiac and noncardiac death, nonfatal acute myocardial infarction, hospital
      admission for unstable angina and need for coronary artery bypass graft surgery
      or percutaneous transluminal coronary angioplasty were recorded. RESULTS: A total
      of 145 events occurred in 120 (23.1%) of 520 patients. Patients with more than
      six episodes had an event rate of 32.5% compared with 25.0% for patients with two
      to six episodes and 13.2% for patients with less than two episodes (p < 0.001).
      Hard events (death, acute myocardial infarction, hospital admission for unstable
      angina pectoris) were more frequent in patients with two or more ischemic
      episodes (12.2% vs. 4.7%, p = 0.0049). Patients with a 100% response rate of
      transient ischemic episodes during the TIBBS trial had a 17.5% event rate at 1
      year compared with 32.3% for non-100% responders (p = 0.008). Patients receiving
      bisoprolol during the TIBBS tria had a lower event rate (22.1%) at 1 year than
      patients randomized to nifedipine (33.1%, p = 0.033). CONCLUSIONS: In patients
      with stable angina pectoris, frequent episodes of transient ischemia are a marker
      for an increased event rate. A 100% response to medical treatment reduces the
      event rate. The greater reduction of ischemia with bisoprolol than nifedipine
      during the TIBBS trial translated into an improved outcome at 1 year.

PMID- 8752791
TI  - An emergency department-based protocol for rapidly ruling out myocardial ischemia
      reduces hospital time and expense: results of a randomized study (ROMIO).
AB  - OBJECTIVES: We tested the hypothesis that an emergency department-based protocol
      for rapidly ruling out myocardial ischemia would reduce hospital time and expense
      but maintain diagnostic accuracy. BACKGROUND: Patients with a missed diagnosis of
      myocardial infarction have a high mortality rate; however, providing routine
      hospital care to low risk patients may not be time- or cost-effective. METHODS:
      One hundred low risk patients were entered into the study and randomized either
      to an emergency department-based rapid rule-out protocol (n = 50) or to routine
      hospital care (n = 50). Patients receiving routine care were managed by their
      attending physicians. The rapid protocol included serum enzyme testing at 0, 3, 6
      and 9h, serial electrocardiograms with continuous ST segment monitoring and, if
      results were negative, a predischarge graded exercise test. Study patients were
      also compared with 160 historical control subjects. RESULTS: Myocardial
      infarction or unstable angina occurred in 6% of patients within 30 days; no
      diagnoses were missed. By intention to treat analysis (n = 50 in each group), the
      hospital stay was shorter and charges were lower with the rapid protocol than
      with routine care (p = 0.001). Among patients in whom ischemia was ruled out,
      those assigned to the rapid protocol had a shorter hospital stay (median 11.9 vs.
      22.8 h, p = 0.0001) and lower initial ($893 vs $1,349, p = 0.0001) and 30-day
      ($898 vs. $1,522, p = 0.0001) hospital charges than did patients given routine
      care. In historical control subjects, the hospital stay was longer (median 34.5
      h, p = 0.001 vs. either group) and charges greater (median $2,063, p = 0.001, vs
      rapid protocol, p = 0.02, vs. routine care group). CONCLUSIONS: In low risk
      patients who present to the emergency department with chest pain, the rapid
      protocol ruled out myocardial infarction and unstable angina more quickly and
      cost-effectively than did routine hospital care.

PMID- 8752792
TI  - Effective risk stratification using exercise myocardial perfusion SPECT in women:
      gender-related differences in prognostic nuclear testing.
AB  - OBJECTIVES: This study was designed to evaluate the incremental prognostic value
      over clinical and exercise variables of rest thallium-201/exercise technetium-99m
      sestamibi single-photon emission computed tomography (SPECT) in women compared
      with men and to determine whether this test can be used to effectively risk
      stratify patients of both genders. BACKGROUND: To minimize the previously
      described gender-related bias in the evaluation of coronary artery disease in
      women, there is a need to identify a noninvasive testing strategy that is able to
      accurately and effectively risk stratify women. METHODS: We identified 4,136
      consecutive patients (2,742 men, 1,394 women) who underwent dual-isotope SPECT.
      The incremental value of nuclear testing was determined using both a stepwise Cox
      proportional hazards model and Kaplan-Meier survival analysis. Receiver operating
      characteristic curve analysis was performed to determine test discrimination for
      high risk patients in men and women. RESULTS: The patient population was followed
      up for 20 +/- 5 months for events (cardiac death or nonfatal myocardial
      infarction). During this time, 63 myocardial infarctions and 32 cardiac deaths
      occurred in the men, and 31 myocardial infarctions and 14 cardiac deaths occurred
      in the women. Nuclear testing significantly stratified both men and women
      irrespective of their rest electrocardiogram. Cox proportional hazards analysis
      revealed that nuclear testing added incremental prognostic value in both men and
      women after inclusion of the most predictive clinical exercise variables (overall
      chi-square 89 in men vs. 120 in women, p < 0.005). Kaplan-Meier survival analysis
      demonstrated that nuclear testing further stratified men and women with both
      intermediate to high and low prescan likelihoods of coronary artery disease (p <
      0.005 for all). Receiver operating characteristic curve analysis demonstrated
      superior discrimination for the nuclear scan results in identifying high risk
      women than men (area under the curve: 0.84 +/- 0.03 vs 0.71 +/- 0.03 in men, p <
      0005). The odds ratio comparing event rates in patients with women than in men,
      suggesting superior stratification using nuclear testing in women. CONCLUSIONS:
      Dual-isotope myocardial perfusion imaging yields incremental prognostic value in
      both men and women. This modality identifies low risk women and men equally well
      but relatively high risk women more accurately than relatively high risk men and,
      thus, is able to stratify women more effectively than men.

PMID- 8752793
TI  - Does stress echocardiography predict the site of future myocardial infarction? A
      large-scale multicenter study. EPIC (Echo Persantine International Cooperative)
      and EDIC (Echo Dobutamine International Cooperative) study groups.
AB  - OBJECTIVES: We sought to assess whether the site of future myocardial infarction
      can be predicted on the basis of induced dyssynergy ("area at risk") recognized
      by stress echocardiography. BACKGROUND: The severity and extent of stress-induced
      dyssynergy are strong predictors of subsequent major cardiac events. However,
      high grade stenotic lesions are not strictly associated with the site of future
      coronary occlusions. METHODS: From the stress echocardiography multicenter trials
      data bank, we selected 70 patients (56 men; mean age +/- SD 58 +/- 11 years)
      meeting the following inclusion criteria: 1) dipyridamole (n = 53) or dobutamine
      (n = 17) stress echocardiography; 2) a spontaneously occurring infarction, with
      no intercurrent revascularization procedure between the initial study and the
      infarction; and 3) a follow-up rest echocardiogram obtained 41 +/- 90 days after
      the infarction. RESULTS: A complete ischemia-infarction mismatch (infarct-related
      dysfunction in a patient with negative stress test results) occurred in 29
      patients (41%). A partial mismatch (ischemic dysfunction in a territory different
      from the infarct area) occurred in nine patients (13%). A match (ischemia-related
      and infarction-related dyssynergy involving the same region) occurred in 32
      patients (46%). The average time interval between the stress examination and the
      occurrence of infarction or reinfarction was 144 +/- 160 days in patients with a
      match and 439 +/- 622 days in patients with a mismatch (p < 0.05). CONCLUSIONS:
      Induced ischemia (imaged as transient dyssynergy by pharmacologic stress
      echocardiography) inconsistently identifies the site of future infarction. The
      majority of spontaneous coronary occlusions leading to infarction are unheralded
      by induced ischemia. However, most infarctions occurring within 1 year of stress
      testing are in the area identified as ischemic during testing.

PMID- 8752794
TI  - Stress echocardiography in elderly patients with coronary artery disease:
      applicability, safety and prognostic value of dobutamine and adenosine
      echocardiography in elderly patients.
AB  - OBJECTIVES: Our aim was to determine the applicability, safety and prognostic
      value of adenosine and dobutamine stress echocardiography in patients > or = 70
      years old. BACKGROUND: These tests are sometimes mandatory because of
      difficulties and inaccuracies in interpreting traditional electrocardiographic
      stress tests. Furthermore, if these tests could be used to avoid coronary
      arteriography and cardiac catheterization, they would become essential in the
      care of the elderly, whose numbers are increasing. METHODS: We performed coronary
      arteriography and dobutamine and adenosine stress echocardiographic tests in 120
      patients (72 men) > or = 70 years old who entered the hospital because of chest
      pain and had known or suspected coronary artery disease. The stress tests were
      performed on separate days, within 2 weeks of coronary arteriography. Both the
      arteriograms and the echocardiograms were analyzed by two experts who had no
      knowledge of the patients' other data or the other interpreter's report. Tests
      were judged to have positive or negative results, and the patients were followed
      up for the development of cardiac events. Univariate and multivariate analyses
      and other statistical modalities were applied for comparisons. RESULTS:
      Documented coronary artery disease was found in 89 patients. During the 14 +/- 7
      of follow-up, cardiac events developed in 50 patients, including 3 (7.9%) of 38
      patients with negative dobutamine and 12 (20.7%) of 58 patients with negative
      adenosine test results. Demonstration of any abnormality on stress
      echocardiography was an independent factor for cardiac events, both for
      dobutamine (relative risk 7.3) and for adenosine (relative risk 3.0). Both
      cessation of dobutamine or adenosine tests and diagnosis of disease in two or
      more coronary vessels were also independent predictors. ST segment depression >
      or = 1mm was related to future events only with the dobutamine test. CONCLUSIONS:
      These echocardiographic stress tests proved safe and well tolerated. They
      successfully stratified this cohort of elderly patients with coronary artery
      disease to low or high risk subgroups for subsequent cardiac events.

PMID- 8752795
TI  - Predictive value of low dose dobutamine transesophageal echocardiography and
      fluorine-18 fluorodeoxyglucose positron emission tomography for recovery of
      regional left ventricular function after successful revascularization.
AB  - OBJECTIVES: This study was designed to assess the predictive value of myocardial
      viability diagnosed by dobutamine transesophageal echocardiography and fluorine
      (F)-18 fluorodeoxyglucose positron emission tomography for left ventricular
      functional recovery after revascularization in patients with chronic left
      ventricular dysfunction. BACKGROUND: The identification of akinetic but viable
      myocardium is of particular importance for the selection of patients with a
      compromised left ventricle who will benefit from coronary revascularization.
      METHODS: Multiplane rest and dobutamine transesophageal echocardiography
      (dobutamine, 5 and 10 microg/min per kg) studies and F-18 fluorodeoxyglucose
      positron emission tomographic studies at rest were performed in 2 patients with
      1) previous myocardial infarction and regional akinesia, 2) a stenosed infarct
      related coronary artery, and 3) a patent infarct-related vessel after
      revascularization. A basally akinetic segment was considered viable by
      transesophageal echocardiography if dobutamine-induced contractile reserve could
      be observed. Viability by positron emission tomography was defined as F-18
      fluorodeoxyglucose uptake > or = 50% of the maximal uptake in a region with
      normal wall motion. Recovery of regional left ventricular function 4 to 6 months
      after revascularization was diagnosed by transesophageal echocardiography if > or
      = 50% of segments akinetic at baseline had improved wall thickening. RESULTS:
      Dobutamine transesophageal echocardiography identified viable infarct regions in
      25 (59%) of 42 patients, and F-18 fluorodeoxyglucose positron emission tomography
      in 30 (71%) of 42 patients, yielding diagnostic agreement in 86% of patients.
      Sensitivity and specificity for prediction of left ventricular functional
      recovery in individual patients was 92% and 88%, respectively, for dobutamine
      transesophageal echocardiography versus 96% and 69% for F-18 fluorodeoxyglucose
      positron emission tomography. Segments remaining akinetic after revascularization
      had a significantly lower (p < 0.001) F-18 fluorodeoxyglucose uptake (48 +/- 15%)
      than that (73 +/- 15%) of segments with recovery of regional left ventricular
      function. CONCLUSIONS: Both dobutamine transesophageal echocardiography and F-18
      fluorodeoxyglucose positron emission tomography were highly sensitive in
      predicting functional recovery of chronically kinetic or dyskinetic myocardium
      after successful revascularization. Thus, dobutamine transesophageal
      echocardiography is a clinically valuable alternative to F-18 fluorodeoxyglucose
      positron emission tomography for assessing residual viability and predicting
      functional recovery after revascularization.

PMID- 8752796
TI  - Electrophysiologic effects of ischemic preconditioning on QT dispersion during
      coronary angioplasty.
AB  - OBJECTIVES: The aim of this study was to examine the effect of ischemic
      preconditioning on the manner of ventricular repolarization by assessing the
      change in QT dispersion during coronary angioplasty. BACKGROUND: QT interval
      dispersion reflects regional variations in ventricular repolarization and cardiac
      electrical instability. Previous studies have suggested that increased QT
      dispersion is associated with an increased incidence of malignant ventricular
      arrhythmias, whereas brief episodes of myocardial ischemia can render the heart
      more resistant to subsequent ischemic episodes, a phenomenon called ischemic
      preconditioning. METHODS: To assess the effects of ischemic preconditioning on
      myocardial repolarization by examining the change in QT dispersion during
      coronary angioplasty, we studied 47 consecutive patients (39 men and 8 women;
      mean age 57 +/- 16 years). QT dispersion was measured after each balloon
      inflation during coronary angioplasty. Statistical analysis was performed by
      using repeated measurement of analysis of variance. RESULTS: There were
      significant differences in QT dispersion as the number of balloon inflations
      increased (mean +/- SD 52 +/- 14, 42 +/- 11, 36 +/- 9, 31 +/- 10 and 29 +/- 11
      ms, respectively [p < 0.01], for the first, second, third, fourth and fifth
      balloon inflations). The magnitude of decrease in QT dispersion was significant
      in the first and second balloon inflations, then became insignificant with later
      inflations. CONCLUSIONS: These data indicate that the gradual decrease in QT
      dispersion provoked by coronary artery occlusion and reperfusion during coronary
      angioplasty may be associated with electrophysiologic effects of ischemic
      preconditioning on myocardium in the human heart.

PMID- 8752797
TI  - Primary stent implantation without coumadin in acute myocardial infarction.
AB  - OBJECTIVES: We tested the feasibility and efficacy of primary stent implantation
      without Coumadin in 74 patients within 8 h of the onset of acute myocardial
      infarction. BACKGROUND: Although stent implantation in patients with effort
      angina provides better short- and long-term outcomes than balloon angioplasty, it
      is not clear whether primary stent implantation is applicable or effective in
      acute myocardial infarction. METHODS: Primary sent implantation was attempted
      when 1) the lesion was not located distally in the main coronary branches, 2) the
      coronary artery did not show any severe calcification or excessive bending
      proximal to the lesion on fluoroscopy, and 3) the arterial diameter was > or =
      2.5 mm. The results (group S) were compared with those of primary balloon
      angioplasty (group P). Poststenting regimens contained ticlopidine and aspirin
      without Coumadin. Poststenting inflation was performed with > or = 12 atm.
      RESULTS: Stent implantation was successful in 72 patients. Stent thrombosis was
      noted in only one patient who was not given ticlopidine, aspirin or Coumadin. The
      rates of restenosis and frequency of major clinical events during the hospital
      period in groups S and P were 0% versus 13.2% (p = 0.007) and 2.8% versus 18.6%
      (p = 0.009), respectively. Kaplan-Meier analysis demonstrated that cumulative 90
      day clinical event-free rates in groups P and S were 98.1 +/- 16.0% versus 79.4
      +/- 43.7% (p = 0.0068), and that 180-day rates were 86.5 +/- 38.4% versus 64.2 +/
      49.7% (p = 0.014). CONCLUSIONS: Primary stent implantation can improve clinical
      outcomes of patients with acute myocardial infarction when the stent is dilated
      adequately and antiplatelet drugs are used.

PMID- 8752798
TI  - Ten-year follow-up of percutaneous transluminal coronary angioplasty for proximal
      left anterior descending coronary artery stenosis in 351 patients.
AB  - OBJECTIVES: We sought to evaluate the short- and long-term results of balloon
      angioplasty for stenoses in the proximal left anterior descending coronary
      artery. BACKGROUND: Both the supposedly high rate of acute complications and
      relatively poor long-term results of balloon angioplasty for stenoses in the
      proximal left anterior descending coronary artery have led to a search for
      alternative interventional techniques. METHODS: We analyzed the success rates and
      long-term follow-up results in 351 consecutive patients who underwent balloon
      angioplasty for stenosis of the left anterior descending coronary artery proximal
      to its first side branch. The power of the study was >80% in detecting a
      difference of 9% in the proportion of patients who survived at 10 years, assuming
      an 80% survival rate in the control group. RESULTS: There were 60 ostial and 291
      nonostial stenoses. Follow-up lasted a median of 85 months (range 0 to 137) and
      was 100% complete. The angiographic success rate was 90.9%. The clinical success
      rate was 86.3%. Nine patients (2.6%) died, 17 (4.8%) needed emergency coronary
      artery bypass graft surgery, and 10 (2.8%) developed a myocardial infarction.
      Several patients had subsequent complications. The success and complication rates
      were not significantly different for patients with ostial and nonostial stenoses.
      Ten years after balloon angioplasty, freedom from mortality was 80%, freedom from
      cardiac death was 87%, freedom from myocardial infarction was 84%, freedom from
      vessel-related reinterventions was 66%, and freedom from angina pectoris was 33%.
      There were more reinterventions for ostial stenoses, with a 1-year relative risk
      of ostial versus nonostial stenoses for related reinterventions of 1.7 (95%
      confidence interval 1 to 2.8, p = 0.049). CONCLUSIONS: More than 10 years ago,
      balloon angioplasty for stenoses in the proximal left anterior descending
      coronary artery, either ostial or nonostial, had a high success rate. Although
      the long-term results are satisfactory, ostial stenoses are associated with a
      higher early clinical restenosis rate requiring more reinterventions.

PMID- 8752799
TI  - Long-term clinical outcome after stent implantation in saphenous vein grafts.
AB  - OBJECTIVES: We sought to determine the role of stent implantation in vein grafts
      by evaluating the long-term clinical outcome and estimated event-free survival at
      5 years in 62 patients and by comparing our data with those of other treatment
      modalities previously reported. BACKGROUND: Patients with recurrent angina after
      coronary artery bypass graft surgery pose a problem. Stent implantation has been
      advocated in an effort to avoid repeat operation and to address the limitations
      of balloon angioplasty. METHODS: Patients undergoing stenting of a vein graft
      were entered into a dedicated data base. They were screened for death,
      infarction, bypass surgery and repeat angioplasty. Procedure-related events were
      included in the follow-up analysis. Survival and event-free survival curves were
      constructed by the Kaplan Meier method. RESULTS: A total of 93 stents (84
      Wallstent and 9 Palmaz-Shatz) were implanted in 62 patients. During the in
      hospital period seven patients (11%) sustained a major cardiac event: two deaths
      (3%), two myocardial infarctions (3%) and three urgent bypass surgeries (5%). The
      clinical success rate, therefore, was 89%. During the follow-up period (median
      2.5 years, range 0 to 5.9), another five patients (8%) died, 14 (23%) sustained a
      myocardial infarction, 12 (20%) underwent bypass surgery, and 14 (23%) underwent
      angioplasty. The estimated 5-year survival and event-free survival rates (free
      from infarction, repeat surgery and repeat angioplasty) were (mean +/- SD) 83 +/-
      5% (95% confidence interval [CI] 73% to 93%) and 30 +/- 7% (95% CI 16% to 44%),
      respectively. CONCLUSIONS: The in-hospital outcome of patients who underwent
      stent implantation in a vein graft is acceptable, but the long-term clinical
      outcome is poor. It is unlikely that mechanical intervention alone will provide a
      satisfactory or definite answer for the patient with graft sclerosis over the
      long term.

PMID- 8752800
TI  - Comparison of angioscopy, intravascular ultrasound imaging and quantitative
      coronary angiography in predicting clinical outcome after coronary intervention
      in high risk patients.
AB  - OBJECTIVES: The purpose of this study was to identify qualitative or quantitative
      variables present on angioscopy, intravascular ultrasound imaging or quantitative
      coronary arteriography that were associated with adverse clinical outcome after
      coronary intervention in high risk patients. BACKGROUND: Patients with acute
      coronary syndromes and complex lesion morphology on angiography are at increased
      risk for acute complications after coronary angioplasty. Newer devices that
      primarily remove atheroma have not improved outcome over that of balloon
      angioplasty. Intravascular imaging can accurately identify intraluminal and
      intramural histopathologic features not adequately visualized during coronary
      arteriography and may provide mechanistic insight into the pathogenesis of abrupt
      closure and restenosis. METHODS: Sixty high risk patients with unstable coronary
      syndromes and complex lesions on angiography underwent angioscopy (n = 40) and
      intravascular ultrasound imaging (n = 46) during interventional procedures. In 26
      patients, both angioscopy and intravascular ultrasound were performed in the same
      lesion. All patients underwent off-line quantitative coronary arteriography.
      Coronary interventions included balloon (n = 21) and excimer laser (n = 4)
      angioplasty, directional (n = 19) and rotational (n = 6) atherectomy and stent
      implantation (n = 11). Patients were followed up for 1 year for objective
      evidence for recurrent ischemia. RESULTS: Patients whose clinical presentation
      included rest angina or acute myocardial infarction or who received thrombolytic
      therapy within 24 h of procedure were significantly more likely to experience
      recurrent ischemia after intervention. Plaque rupture or thrombus on preprocedure
      angioscopy or angioscopic thrombus after intervention were also significantly
      associated with adverse outcome. Qualitative or quantitative variables on
      angiography, intravascular ultrasound or off-line quantitative arteriography were
      not associated with recurrent ischemia on univariate analysis. Multivariate
      predictors of recurrent ischemia were plaque rupture on preprocedure angioscopy
      (p < 0.05, odds ratio [OR] 10.15) and angioscopic thrombus after intervention (p
      < 0.05, OR 7.26). CONCLUSIONS: Angioscopic plaque rupture and thrombus were
      independently associated with adverse outcome in patients with complex lesions
      after interventional procedures. These features were not identified by either
      angiography or intravascular ultrasound.

PMID- 8752801
TI  - Cost-efficacy modeling of catheter reuse for percutaneous transluminal coronary
      angioplasty.
AB  - OBJECTIVES: Our goal was to provide the range of cost savings associated with
      various catheter reuse strategies. BACKGROUND: Percutaneous transluminal coronary
      angioplasty catheters are commonly reused in several countries outside the United
      States. However, the cost-effectiveness of such reuse strategies has not been
      evaluated. METHODS: Three theoretical models of catheter reuse were constructed
      using the actual costs for treating patients with coronary angioplasty at the
      Cleveland Clinic. Costs were calculated based on the number of balloon catheters,
      the amount of contrast agent used and the rates for urgent revascularization that
      were observed in a prospective Canadian study on catheter reuse. RESULTS: The
      median cost to treat a lesion by means of coronary angioplasty using new
      catheters was $8,800 per patient. In reuse models, the potential to reduce cost
      depended on the number of balloon catheters used and the rates of urgent
      revascularization. The "best care" scenario offered a potential savings of $480
      (5.5% of total in-hospital cost), whereas the "worst case" scenario resulted in
      an increased cost of $1,075 (12.2% of total in-hospital cost) compared with the
      single-use strategy. Cost of the "likely case" scenario was similar to that of
      the single-use strategy. Sensitivity analyses identified the different rates of
      revascularization and cost of balloon catheters required to offset potential
      savings in each strategy. CONCLUSIONS: Although reusing coronary angioplasty
      catheters may reduce total in-hospital costs, even a modest increase in
      complications requiring urgent revascularization may offset any potential
      savings. However, if an increase in complications and procedure time can be
      avoided, the reuse strategy has significant economic potential and, ultimately,
      may be extended to other percutaneous coronary interventional equipment.

PMID- 8752802
TI  - Should percutaneous transluminal coronary angioplasty catheters be reused?

PMID- 8752803
TI  - Which patient benefits from early angiotensin-converting enzyme inhibition after
      myocardial infarction? Results of one-year serial echocardiographic follow-up
      from the Captopril and Thrombolysis Study (CATS).
AB  - OBJECTIVES: In this study we sought to investigate the effect of intervention
      with captopril within 6 h of the onset of myocardial infarction on left
      ventricular volume and clinical symptoms of heart failure in relation to infarct
      size during a 1-year follow-up period. BACKGROUND: Remodeling of the heart starts
      in the early phase of myocardial infarction and is associated with an adverse
      prognosis. Angiotensin-converting enzyme inhibition started in the subacute or
      late phase after myocardial infarction has been shown to improve prognosis.
      METHODS: In the Captopril and Thrombolysis Study, 298 patients with a first
      anterior myocardial infarction treated with intravenous streptokinase were
      randomized to receive either oral captopril (25 mg three times a day) or placebo.
      The left ventricular volume index was assessed by two-dimensional
      echocardiography within 24 h, on days 3, 10 and 90 and after 1 year. RESULTS: A
      small but significant increase in left ventricular volume indexes was observed
      after 12 months. Using a random coefficient model, no significant treatment
      effect on left ventricular volumes could be detected. In contrast, when survival
      models were used, the occurrence of left ventricular dilation was significatnly
      lower in captopril-treated patients (p = 0.018). In addition, the incidence of
      heart failure was lower in the captopril group (p < 0.03). This effect appeared
      early and was most obvious in patients with a medium-sized infarct (p = 0.04) and
      was not present in large infarcts. CONCLUSIONS: Very early treatment with
      captopril after myocardial infarction significantly reduces the occurrence of
      early dilation and the progression to heart failure. These data underscore the
      importance of early treatment. Furthermore, patients with intermediate infarct
      size benefit the most from this treatment strategy.

PMID- 8752804
TI  - What is the risk of sudden cardiac death in patients presenting with
      hemodynamically stable sustained ventricular tachycardia after myocardial
      infarction?
AB  - OBJECTIVES: This study sought to determine the long-term risk of sudden cardiac
      death in patients with hemodynamically stable sustained ventricular tachycardia
      complicating coronary artery disease. BACKGROUND: The prognosis and risk of
      sudden cardiac death in patients with a history of myocardial infarction and
      ventricular tachyarrhythmias have not been clearly defined. Prior studies are
      limited by a short follow-up period and by inclusion of patients with
      heterogeneous cardiac diseases and presenting arrhythmias. METHODS: A
      retrospective cohort analysis was performed on data from 124 patients, followed
      up for a mean of 36 +/- 30 months, who received electrophysiologically guided
      therapy for hemodynamically stable ventricular tachycardia after remote
      myocardial infarction. RESULTS: Seventy-eight patients were treated
      pharmacologically (medical group), and 46 patients underwent map-guided
      subendocardial resection (surgical group). Nine patients (7.3%) died suddenly, 5
      (4.0%) died of noncardiac causes, 9 (7.3%) died of a perioperative complication,
      and 20 (23.4%) died of other cardiac causes. At 1, 2 and 3 years, sudden death
      occurred at cumulative rates of 2 +/- 1%, 3 +/- 2% and 7 +/- 3%, whereas total
      mortality was 20 +/- 4%, 28 +/- 4% and 32 +/- 5% (mean +/- SD). Sudden cardiac
      death (p = 0.047) and total mortality (p = 0.036) were higher in patients with
      multivessel disease and were similar for both treatment groups. CONCLUSIONS:
      Although the overall mortality in postinfarction patients presenting with
      hemodynamically stable ventricular tachycardia treated with
      electrophysiologically guided antiarrhythmic therapy is high, the risk of sudden
      death in these patients appears to be low (average 2.4%/year).

PMID- 8752805
TI  - Efficacy of intravenous ibutilide for rapid termination of atrial fibrillation
      and atrial flutter: a dose-response study.
AB  - OBJECTIVES: Currently available antiarrhythmic drugs have limited efficacy for
      short-term, rapid termination of atrial fibrillation and atrial flutter.
      BACKGROUND: Ibutilide fumarate is an investigational class III antiarrhythmic
      agent that prolongs repolarization by increasing the slow inward sodium current
      and by blocking the delayed rectifier current. It can be administered
      intravenously and has a rapid onset of electrophysiologic effects. METHODS: The
      efficacy and safety of ibutilide were studied in 200 patients with atrial flutter
      > 3 h in duration or atrial fibrillation 3 h to 90 days in duration. Patients
      were randomized to receive a single intravenous dose of placebo or an infusion of
      ibutilide fumarate at 0.005, 0.010, 0.015 or 0.025 mg/kg body weight over 10 min.
      Conversion was defined as termination of the atrial arrhythmia during or within
      60 min after infusion. Forty-one patients received placebo and 159 received
      ibutilide (0.005 mg/kg [n = 41], 0.010 mg/kg [n = 40], 0.015 mg/kg [n = 38] or
      0.025 mg/kg [n = 40]). RESULTS: The arrhythmia terminated in 34% of drug-treated
      patients. The rates of successful arrhythmia termination were 3% for placebo and
      12%, 33%, 45% and 46%, respectively, for 0.005-, 0.010-, 0.015- and 0.025-mg/kg
      ibutilide. The placebo and 0.005-mg/kg ibutilide groups had lower success rates
      than all other dose groups (p < 0.05). The mean time to termination of the
      arrhythmia was 19 min (range 3 to 70) from the start of infusion. Successful
      arrhythmia termination was not affected by enlarged left atrial diameter,
      decreased ejection fraction, presence of valvular heart disease or the use of
      concomitant medications (beta-adrenergic blocking agents, calcium channel
      blocking agents or digoxin). Arrhythmia termination was not predicted by the
      magnitude of corrected QT interval prolongation but was associated with a shorter
      duration of atrial arrhythmia. The most frequent adverse events in ibutilide
      treated patients were sustained and nonsustained polymorphic ventricular
      tachycardia (3.6%). All patients with sustained polymorphic ventricular
      tachycardia were successfully treated with direct current cardioversion and had
      no recurrence. The occurrence of proarrhythmia did not correlate with ibutilide
      plasma concentration. CONCLUSIONS: These data demonstrate that ibutilide is able
      to rapidly terminate atrial fibrillation and atrial flutter.

PMID- 8752806
TI  - Reversal of reentry and acceleration due to double-wave reentry: two mechanisms
      for failure to terminate tachycardias by rapid pacing.
AB  - OBJECTIVES: We sought to demonstrate mechanisms by which rapid pacing can cause
      conduction block without terminating reentry. BACKGROUND: Rapid pacing can fail
      to terminate or can accelerate tachycardias in patients. Mechanisms for these
      responses are poorly understood. METHODS: We studied reentry in the canine atrial
      tricuspid ring and a left ventricular ring in vitro in 12 preparations.
      Activations were recorded from 10 sites around the ring, and monophasic action
      potentials were recorded from critical sites of block. Rapid pacing at cycle
      lengths that intermittently caused conduction block was performed at multiple
      sites. RESULTS: Action potential alternans contributed to block of an orthodromic
      impulse during rapid pacing. When pacing continued for two stimuli after
      orthodromic block, a second episode of block could reverse the direction of
      tachycardia. Continued pacing at this site was likely to produce block of an
      antidromic impulse, which may initiate double-wave reentry. Double-wave reentry
      could be sustained or nonsustained. Its cycle length was 56% to 77% of the single
      wave cycle length. The ratio of double-wave cycle length to single-wave cycle
      length was inversely correlated with the relative excitable gap (p < 0.01).
      Double-wave reentry can be a mechanism for persistent cycle length alternation
      during tachycardia. CONCLUSIONS: Successful termination of reentry by rapid
      pacing required block of an othrodromic impulse and stopping pacing within one
      stimulus after orthodromic block. Reversal of reentry makes the circuit resistant
      to termination from this site of pacing. Antidromic block can cause acceleration
      due to double-wave reentry when there is a substantial excitable gap.

PMID- 8752807
TI  - Adenosine: potential modulator for vasovagal syncope.
AB  - OBJECTIVES: This study examined the hypothesis that adenosine could provoke a
      vasovagal response in susceptible patients. Mechanisms of the vasovagal response
      were further explored by studying the adenosine-mediated reactions. BACKGROUND:
      Increased sympathetic activity is frequently observed before vasovagal syncope.
      Recent studies have demonstrated that adenosine, in addition to its direct
      bradycardiac and vasodilatory effects, can increase sympathetic discharge by
      activating cardiovascular afferent nerves. METHODS: The effects of adenosine and
      head-up tilt-table testing with or without isoproterenol were prospectively
      evaluated in 85 patients examined for syncope after negative results of
      electrophysiologic testing (51 men and 34 women, mean [+/- SD] age 61 +/- 17
      years). Adenosine bolus injections of 6 mg and 12 mg were sequentially
      administered to patients in the upright position. The same protocol was
      implemented in 14 normal control subjects (7 men and 7 women, mean [+/- SD] age
      38 +/- 10 years). RESULTS: Transient hypertension or tachycardia was observed in
      57 (67%) and 20 (24%) patients after administration of 6 mg and 12 mg of
      adenosine, respectively, during the immediate phase (first 15 s), suggesting
      direct sympathetic activation. Hypotension and reflex tachycardia were observed
      in all patients during the delayed phase (15 to 60 s after adenosine injection),
      suggesting baroreceptor unloading. A vasovagal response was induced in 22 (26%)
      and 29 (34%) patients after adenosine administration and during tilt-table
      testing. Inducibility of a vasovagal response by these two methods was comparable
      (p = 0.12). Of the control subjects, one (7%) had a vasovagal response after
      adenosine administration and one (7%) had a positive response during tilt-table
      testing. CONCLUSIONS: These observations support the idea that adenosine is an
      endogenous modulator of the cardiac excitatory afferent nerves. Sympathetic
      activation by adenosine can be direct (i.e., cardiac excitatory afferent nerves)
      and indirect (i.e., vasodilation and reflex sympathetic activation). Adenosine
      could be an important modulator in triggering a vasovagal response in susceptible
      patients during examination for syncope.

PMID- 8752809
TI  - The DD genotype of the angiotensin-converting enzyme gene is associated with
      increased mortality in idiopathic heart failure.
AB  - OBJECTIVES: The aim of the present study was to investigate the association
      between the homozygous DD (deletion) genotype of the angiotensin-converting
      enzyme gene and survival and cardiac function in patients with idiopathic
      congestive heart failure. BACKGROUND: The DD genotype gene is a linkage marker
      for an etiologic mutation at or near the angiotensin-converting enzyme gene and
      has been associated with increased risk for the development of coronary artery
      disease, left ventricular hypertrophy and left ventricular dilation after
      myocardial infarction. We investigated the association between this angiotensin
      converting enzyme genotype and mortality in a population-based cohort of patients
      with idiopathic congestive heart failure. METHODS: The genotype was determined in
      193 patients recruited from a large unselected population of patients with
      congestive heart failure (n = 2,711). The patients were studied with
      echocardiography, and survival data were obtained after 5 years of follow-up. A
      control group from the general population (n = 77) was studied by a similar
      procedure. RESULTS: The frequency of the D allele was not significantly different
      in the study and control groups (0.57 vs 0.56, p = NS). Long-term survival was
      significantly worse in the patients with the DD genotype than in the remaining
      patients (5-year survival rate 49% vs. 72%, p = 0.0011 as assessed by log rank
      test). The independent importance of the DD genotype for prognosis was verified
      by a multivariate Cox proportional hazards analysis, by which the odds ratio for
      mortality and the DD genotype was 1.69 (95% confidence interval 1.01 to 2.82).
      The only significant difference in cardiac function data between the two groups
      was an increase in left ventricular mass index in the DD group (153 +/- 57 vs 134
      +/- 44 g/m2, p = 0.019). CONCLUSIONS: Angiotensin-converting enzyme gene DD
      polymorphism was associated with poorer survival and an increase in left
      ventricular mass in patients with idiopathic heart failure. The results suggest a
      possible pathophysiologic pathway between angiotensin-converting enzyme gene
      polymorphism, angiotensin-converting enzyme activity, myocardial hypertrophy and
      survival. Therefore, the DD genotype may be a marker of poor prognosis in
      patients with congestive heart failure.

PMID- 8752808
TI  - Digoxin reduces cardiac sympathetic activity in severe congestive heart failure.
AB  - OBJECTIVES: This study evaluated the effect of digoxin on cardiac sympathetic
      activity in patients with congestive heart failure. BACKGROUND: Digoxin favorably
      alters autonomic tone in heart failure. Whether it reduces cardiac sympathetic
      drive in the setting of heart failure is unknown. METHODS: Digoxin (0.25 mg
      intravenously) was administered to 12 patients with severe heart failure and
      elevated left ventricular end-diastolic pressure (> 14 mm Hg, Group A), 5
      patients with less severe heart failure who had normal left ventricular end
      diastolic pressure (> 14 mm Hg, Group B) and 6 patients with normal ventricular
      function. Seven additional patients with heart failure were studied as a time
      control group. Cardiac and total body norepinephrine spillover, systemic arterial
      pressure, left ventricular filling pressure and peak positive first derivative of
      left ventricular pressure were all assessed before and 30 min after
      administration of digoxin. RESULTS: In Group A there were no changes in
      hemodynamic variables or total body norepinephrine spillover after digoxin
      administration; however, there was a significant reduction in cardiac
      norepinephrine spillover (263 +/- 70 to 218 +/- 62 pmol/min, mean +/- SEM, p <
      0.001). In contrast, in Group B, digoxin caused a significant increase in cardiac
      norepinephrine spillover that was not associated with any hemodynamic changes or
      a change in total body spillover. There were no hemodynamic changes or a change
      in total body spillover. There were no hemodynamic or spillover changes in the
      time control or normal ventricular function group. CONCLUSIONS: Digoxin, in the
      absence of detectable inotropic or hemodynamic effects, caused a reduction in
      cardiac norepinephrine spillover in patients with heart failure who had elevated
      filling pressures. This finding suggests a potentially beneficial primary
      autonomic action of digoxin in patients with severe heart failure.

PMID- 8752810
TI  - Kinetics of oxygen consumption during and after exercise in patients with dilated
      cardiomyopathy. New markers of exercise intolerance with clinical implications.
AB  - OBJECTIVES: This study analyzed the kinetics of oxygen consumption during and
      after a maximal cardiopulmonary exercise test in patients with dilated
      cardiomyopathy. The prognostic information derived from indexes of recovery was
      also studied. BACKGROUND: Previous studies have examined the kinetics of oxygen
      consumption during a short recovery period in a limited number of patients. To
      our knowledge, no study has examined the prognostic information derived from
      indexes of recovery. METHODS: We studied 153 patients and 55 control subjects. We
      calculated the ratio between total oxygen consumption during exercise and
      recovery, the half-recovery time of peak oxygen consumption, the time constant of
      recovery, the recovery time and the ratio between duration of exercise and
      recovery time. RESULTS: Recovery of oxygen consumption was significantly delayed
      in patients, and this delay was related to the degree of exercise intolerance.
      After a median follow-up period of 439 days, for the total study group, percent
      of predicted peak oxygen consumption (p = 0.003) and ejection fraction (p = 0.03)
      were independent predictors of survival. In a subgroup of patients with moderate
      exercise intolerance (percent peak oxygen consumption > 40%), the ratio between
      total oxygen consumption during exercise and recovery (p = 0.013) and the
      ejection fraction (p = 0.013) were independent predictors of survival.
      CONCLUSIONS: The kinetics of oxygen consumption during recovery was delayed in
      patients with dilated cardiomyopathy. Although indexes of recovery were not
      prognostic markers in the total study group, the ratio between total oxygen
      consumption during exercise and recovery was an independent prognostic marker in
      patients with moderate exercise intolerance.

PMID- 8752811
TI  - Renal vasodilatory effect of endothelial stimulation in patients with chronic
      congestive heart failure.
AB  - OBJECTIVES: This study sought to examine the vasodilatory response of the renal
      circulation to endothelial stimulation in patients with chronic heart failure.
      BACKGROUND: Renal blood flow is often reduced in patients with chronic congestive
      heart failure and may lead to deterioration of renal function. Stimulation of
      renal endothelium has been shown to cause renal vasodilation in animals and in
      isolated human renal artery. The vasoregulatory role of the renal endothelium in
      patients with heart failure has not been evaluated. METHODS: Renal vasodilatory
      effect of endothelial stimulation with acetylcholine was assessed and compared
      with that of endothelial independent vasodilation with nitroglycerin. Both drugs
      were infused into the main renal artery. Renal artery cross-sectional area was
      measured with intravascular ultrasound and renal blood flow velocity with the aid
      of an intravascular Doppler technique. RESULTS: Both drugs caused a significant
      and comparable increase in renal artery cross-sectional area (maximal increase
      [mean +/- SE] 14 +/- 5% with acetylcholine, 15 +/- 5% with nitroglycerin; both
      changes < 0.05 vs. baseline). Acetylcholine also caused a significant reduction
      in renal vascular resistance (maximal reduction 55+/- 6%) and increase in renal
      blood flow (maximal increase 136 +/- 54%). In contrast, nitroglycerin
      administration showed no significant effect on renal vascular resistance and
      blood flow. CONCLUSIONS: Stimulation of endothelium-derived nitric oxide with
      acetylcholine results in a significant vasodilatory effect on both conductance
      and resistance renal blood vessels and leads to a marked reduction in renal
      vascular resistance and enhancement of renal blood blow. Nitroglycerin, an
      exogenous nitric oxide donor, caused a selective vasodilatory effect on renal
      conductance but not on resistance blood vessels and failed to increase renal
      blood flow. These data suggest the possibility that stimulation of endogenous
      nitric oxide production in the kidney could be used as a therapeutic target for
      enhancement of renal flow in patients with heart failure.

PMID- 8752812
TI  - Prognostic value of noninvasive testing one year after orthotopic cardiac
      transplantation.
AB  - OBJECTIVES: We sought to evaluate the prognostic value of routine noninvasive
      testing--stress thallium-201 imaging, rest two-dimensional echocardiography and
      rest equilibrium radionuclide angiography--1 year after cardiac transplantation.
      BACKGROUND: Coronary artery vasculopathy is the most important cause of late
      death after orthotopic cardiac transplantation. Several clinical variables have
      been identified as risk factors for development of coronary vasculopathy.
      Traditional noninvasive diagnostic testing has been shown to be relatively
      insensitive for identifying patients with angiographic vasculopathy. METHODS:
      Results of prospectively acquired noninvasive testing in 47 consecutive
      transplant recipients alive 1 year after transplantation were related to
      subsequent survival. Other clinical variables previously shown to be associated
      with the development of coronary artery vasculopathy were also included in the
      analysis. RESULTS: The 5-year survival rate after cardiac transplantation was
      81%. By univariate analysis, echocardiography (chi-square 9.21) and stress
      thallium-201 myocardial perfusion imaging (chi-square 16.76) were predictive for
      survival, whereas rest equilibrium radionuclide angiography was not. Clinical
      contributors to survival were donor age (chi-square 4.56), number of human
      leukocyte antigen mismatches (chi-square 3.06) and cold ischemic time (chi-square
      3.23). By multivariate analysis, stress myocardial imaging remained the only
      significant predictor of survival (risk ratio 0.27; 95% confidence interval 0.06
      to 0.89). CONCLUSIONS: Normal thallium-201 stress myocardial perfusion imaging 1
      year after cardiac transplantation is an important predictor of 5-year survival.

PMID- 8752813
TI  - Left ventricular systolic and diastolic function assessed with two-dimensional
      and doppler echocardiography in "white coat" hypertension.
AB  - OBJECTIVES: The aim of this study was to investigate left ventricular function in
      subjects with "white coat" hypertension, defined as office arterial diastolic
      pressure > or = 90 and ambulatory daytime pressures < 140/90 mm Hg. BACKGROUND:
      The white coat arterial pressure response may, by influencing left ventricular
      function, have a confounding effect in studies of heart disease. METHODS: Two
      dimensional and Doppler echocardiography combined with the calibrated subclavian
      arterial pulse tracing, were used to assess variables of left ventricular
      function in 26 subjects with white coat hypertension (office arterial diastolic
      pressure > or = 90 and < 115 mm Hg and ambulatory daytime diastolic pressure > or
      = 90 mm Hg) and 32 normotensive subjects. RESULTS: In subjects with white coat
      hypertension, systolic arterial pressure during the echocardiographic examination
      was significantly higher than ambulatory daytime systolic pressure. This pressure
      response was positively related to the ratio of the systolic to diastolic
      pulmonary venous flow peak velocities and to the peak velocity of flow reversion
      during atrial systole; it was inversely related to the ratio of early to late
      mitral flow peak velocities. Left ventricular stroke volume, ejection fraction
      and velocity of circumferential fiber shortening did not differ in the study
      groups, but left ventricular external work and end-systolic wall stress were
      increased in the white coat group. CONCLUSIONS: The arterial pressure response in
      subjects with white coat hypertension is associated with increased left
      ventricular external work, increased end-systolic wall stress and alterations of
      left ventricular filling but normal ejection fraction and velocity of
      circumferential fiber shortening.

PMID- 8752814
TI  - Initial results of combined anterior mitral leaflet extension and myectomy in
      patients with obstructive hypertrophic cardiomyopathy.
AB  - OBJECTIVES: The purpose of this study was to describe the clinical and functional
      results of combined anterior mitral leaflet extension and myectomy in patients
      with hypertrophic obstructive cardiomyopathy. BACKGROUND: Septal myectomy is the
      most commonly performed surgical procedure in patients with hypertrophic
      cardiomyopathy and left ventricular outflow tract obstruction. Because of the
      role of the mitral valve in creating the outflow tract gradient, mitral valve
      replacement or plication is performed in selected cases in combination with
      myectomy, often with better hemodynamic results than those of myectomy alone.
      Mitral valve leaflet extension, in which a glutaraldehyde-preserved autologous
      pericardial patch is used to enlarge the mitral valve along its horizontal axis,
      is a novel surgical approach in patients with hypertrophic obstructive
      cardiomyopathy. METHODS: Eight patients with hypertrophic obstructive
      cardiomyopathy were treated with mitral leaflet extension and myectomy.
      Preoperative and postoperative data (New York Heart Association functional class,
      number of drugs prescribed, width of the interventricular septum, severity of
      mitral valve regurgitation severity of systolic anterior motion of the mitral
      valve and outflow tract gradient) were compared with those of 12 patients
      undergoing myectomy alone. RESULTS: Preoperative evaluation demonstrated that
      mitral regurgitation and systolic anterior motion of the mitral valve were more
      severe in the group undergoing mitral valve extension (p < 0.001 and p < 0.05,
      respectively). There were no deaths associated with either surgical procedure.
      Two patients, both treated by myectomy alone, died during the follow-up period.
      Postoperatively, patients treated with mitral valve extension had less mitral
      regurgitation (p < 0.005), less residual systolic anterior motion (p < 0.001),
      greater improvement in functional class (p = 0.05) and greater reduction in the
      number of drugs (p < 0.005) and in septal thickness (p < 0.05). CONCLUSIONS:
      Mitral leaflet extension in combination with myectomy is a promising new surgical
      approach that may provide superior results to those of myectomy alone. Further
      studies are needed to determine the clinical value of this procedure.

PMID- 8752816
TI  - Follow-up of coil occlusion of patent ductus arteriosus.
AB  - OBJECTIVE: We sought to determine the prevalence and fate of residual ductal
      shunting following coil occlusion of patent ductus arteriosus. BACKGROUND:
      Although transcatheter coil occlusion of patent ductus arteriosus has gained
      popularity, few follow-up data have been reported. METHODS: A review of 75
      patients who underwent coil occlusion was performed. Residual shunting was
      investigated by Doppler echocardiography in follow-up. Angiograms were reviewed
      to obtain minimal ductal diameter and ductal angiographic type. RESULTS: Residual
      shunts were found in 31 patients (41%) on the day of the procedure, and of these,
      spontaneous closure was noted in 17 (55%) at 2 weeks to 20 months of follow-up.
      Of the 75 patients studied, 5 (7%) required a second coil procedure, and 10 (13%)
      remained with persistent residual shunts at most recent follow-up. Actuarial
      analysis estimated a 6 +/- 5% prevalence of residual shunts 20 months after a
      single coil procedure and 3 +/- 3% after all coil procedures. Minimal ductal
      diameter was associated with immediate complete ductal occlusion by a single
      coil. These patients had significantly smaller (p = 0.003) minimal ductal
      diameters (1.2 +/- 0.7 mm) than those who required two coils during their initial
      procedure to achieve immediate occlusion (1.9 +/- 0.7 mm), those who required a
      second coil procedure (2.0 +/- 0.9 mm), those who had spontaneous closure of
      residual shunts (1.9 +/- 0.7 mm) and those with persistent residual shunts (2.0
      +/- 0.9 mm). No association was identified between ductal angiographic type and
      outcome of coil occlusion. No late adverse clinical events of coil occlusion or
      evidence of recanalization was found. CONCLUSIONS: Small residual shunts are
      common after coil embolization of patent ductus arteriosus, but most close
      spontaneously. Actuarial analysis estimates complete closure in 94% at 20 months,
      and reintervention was required in only 7% of patients.

PMID- 8752815
TI  - Dynamic subaortic obstruction: a disease of the mitral valve suitable for
      surgical repair?

PMID- 8752817
TI  - Late ventricular geometry and performance changes of functional single ventricle
      throughout staged Fontan reconstruction assessed by magnetic resonance imaging.
AB  - OBJECTIVES: We sought to test the hypothesis that late ventricular geometry and
      performance changes occur in functional single ventricles as they progress
      through staged Fontan reconstruction. BACKGROUND: Indexes of ventricular geometry
      and performance are important in evaluating the functional state of the heart.
      Magnetic resonance imaging determines these indexes in complex ventricular shapes
      with minimal geometric assumptions. Previous studies have shown that 1 week after
      hemiFontan, the mass/volume ratio markedly increases. METHODS: Multiphase,
      multislice, spin echo (n = 5) and cine (n = 30) magnetic resonance imaging was
      performed in 35 patients with a functional single ventricle (1 week to 12 years
      old) at various stages of Fontan reconstruction (15 in the pre hemiFontan stage,
      11 after [6 to 9 months] the hemiFontan procedure and 9 after [1 to 2 years] the
      Fontan procedure). Volume and mass were calculated at end-systole and end
      diastole. Ventricular output was then obtained. Ventricular centroid motion was
      also calculated. RESULTS: No difference was noted (power > 72%) from the pre
      hemiFontan stage to 6 to 9 months after the hemiFontan procedure in (mean +/- SD)
      end-diastolic volume (104 +/- 24 vs. 123 +/- 40 cc/m2), mass (171 +/- 46 vs. 202
      +/- 61 g/m2), ventricular output (7.9 +/- 2.2 vs. 6.6 +/- 2.4 liters/min per m2)
      or centroid motion (6.9 +/- 2.8 vs. 6.7 +/- 2. mm/m2). Patients in the Fontan
      group demonstrated a marked decrease in all indexes, indicating significant
      volume unloading and decrease in mass and ventricular performance. Mass/volume
      ratio was not significantly different among all three groups. CONCLUSIONS: No
      geometric and performance changes from the volume-loaded stage are noted 6 to 9
      months after the hemiFontan procedure; however, major changes occur 1 to 2 years
      after the Fontan procedure. The dramatic changes in the mass/volume ratio seen
      early after the hemiFontan procedure were not detected at 6 to 9 months.
      Furthermore diminution of mass, volume and ventricular performance are present at
      least 2 years after the Fontan procedure.

PMID- 8752818
TI  - Integrated backscatter for quantification of left atrial spontaneous echo
      contrast.
AB  - OBJECTIVES: This study was designed to develop a quantitative method of
      spontaneous echo contrast (SEC) assessment using integrated backscatter and to
      compare integrated backscatter SEC measurement with independent qualitative
      grades of SEC and clinical and echocardiographic predictors of thromboembolism.
      BACKGROUND: Left atrial SEC refers to dynamic swirling smokelike echoes that are
      associated with low flow states and embolic events and have been graded
      qualitatively as mild or severe. METHODS: We performed transesophageal
      echocardiography in 43 patients and acquired digital integrated backscatter image
      sequences of the interatrial septum to internally calibrate the left ventricular
      cavity and left atrial cavity under different gain settings. Patients were
      independently assessed as having no, mild or severe SEC. We compared intensity of
      integrated backscatter in the left atrial cavity relative to that in the left
      ventricular as well as to the independently assessed qualitative grades of SEC.
      Fourier analysis characterized the temporal variability of SEC. The integrated
      backscatter was compared with clinical and echocardiographic predictors of
      thromboembolism. RESULTS: The left atrial cavity integrated backscatter intensity
      of the mild SEC subgroup was 4.7 dB higher than that from the left ventricular
      cavity, and the left atrial intensity of the severe SEC subgroup was 12.5 dB
      higher than that from the left ventricular cavity. The left atrial cavity
      integrated backscatter intensity correlated well with the qualitative grade.
      Fourier transforms of SEC integrated backscatter sequences revealed a
      characteristic dominant low frequency/high amplitude spectrum, distinctive from
      no SEC. There was a close relationship between integrated backscatter values and
      atrial fibrillation, left atrial size, left atrial appendage flow velocities and
      thrombus. CONCLUSIONS: Integrated backscatter provides an objective quantitative
      measure of SEC that correlates well with qualitative grade and is closely
      associated with clinical and echocardiographic predictors of thromboembolism. The
      relationship between integrated backscatter measures and cardioembolic risk will
      be defined in future multicenter studies.

PMID- 8752819
TI  - Myocardial dysfunction after resuscitation from cardiac arrest: an example of
      global myocardial stunning.
AB  - OBJECTIVES: This study investigated the effect of prolonged cardiac arrest and
      subsequent cardiopulmonary resuscitation on left ventricular systolic and
      diastolic function. BACKGROUND: Cardiac arrest from ventricular fibrillation
      results in cessation of forward blood flow, including myocardial blood flow.
      During cardiopulmonary resuscitation, myocardial blood flow remains suboptimal.
      Once the heart is defibrillated and successful resuscitation achieved, reversible
      myocardial dysfunction, or "stunning," may occur. The magnitude and time course
      of myocardial stunning from cardiac arrest is unknown. METHODS: Twenty-eight
      domestic swine (26 +/- 1 kg) were studied with both invasive and noninvasive
      measurements of ventricular function before and after 10 or 15 min of untreated
      cardiac arrest. Contrast left ventriculograms, ventricular pressures, cardiac
      output, isovolumetric relaxation time (tau) and transthoracic Doppler
      echocardiographic studies were obtained. RESULTS: Twenty-three of 28 animals were
      successfully resuscitated and postresuscitation data obtained. Left ventricular
      ejection fraction showed a significant reduction 30 min after resuscitation (p <
      0.05). Regional wall motion analysis revealed diffuse, global left ventricular
      systolic dysfunction. Left ventricular end-diastolic pressure increased
      significantly in the postresuscitation period (p < 0.05). Isovolumetric
      relaxation time (tau) was significantly increased over baseline by 2 h after
      resuscitation (p < 0.05). Similar findings were noted with the Doppler
      echocardiographic analysis, including a reduction in fractional shortening (p <
      0.05), a reduction in mitral valve deceleration time (p < 0.05) and an increase
      in left ventricular isovolumetric relaxation time at 5 h after resuscitation (p <
      0.05> By 24 h, these invasive and noninvasive variables of systolic and diastolic
      left ventricular function had begun to improve. At 48 h, all measures of left
      ventricular function had returned to baseline levels. CONCLUSIONS: Myocardial
      systolic and diastolic dysfunction is severe after 10 to 15 min of untreated
      cardiac arrest and successful resuscitation. Full recovery of this
      postresuscitation myocardial stunning is seen by 48 h in this experimental model
      of ventricular fibrillation cardiac arrest.

PMID- 8752820
TI  - Transvascular catheter infiltration of the ductus arteriosus with formalin in the
      newborn lamb: a novel method of establishing and maintaining ductal patency.
AB  - OBJECTIVES: This study sought to establish and maintain patency of the ductus
      arteriosus by a new method of transvascular formalin infiltration of the ductus
      arteriosus wall. BACKGROUND: Maintaining patency of the ductus arteriosus
      postnatally is necessary with many forms of congenital heart disease to ensure
      survival until definitive surgical repair. A variety of approaches have to date
      met with variable success. METHODS: Seven newborn lambs underwent catheterization
      at 1 to 5 days of age. A functionally closed ductus arteriosus was traversed with
      a specially designed porous balloon catheter, and the wall was infiltrated with
      10% formalin. The ductus was then further dilated with either a 7- or 8-mm
      diameter balloon. RESULTS: The ductus arteriosus wall was successfully
      infiltrated and dilated in all animals. Two lambs were euthanized within 24 h
      with congestive heart failure from a large ductus, and one lamb was electively
      euthanized 5 days after transvascular infiltration. Four lambs underwent serial
      follow-up catheterizations, one of which required repeat balloon dilation 47 days
      after infiltration. At latest follow-up (mean age [+/- 1 SD] 83 +/- 34 days,
      range 33 to 108), the pulmonary/systemic flow ratio (2.7 +/- 1.2) was unchanged
      from immediately after infiltration (1.9 +/- 0.5, p > 0.1). The narrowest
      diameter of the ductus arteriosus (4.3 +/- 0.4 mm vs. 6.9 +/- 2.6 mm, p > 0.1)
      and its ratio to that of the adjacent descending aorta (0.5 +/- 0.1 vs 0.4 +/-
      0.1, p > 0.1) were also unchanged at latest follow-up. No systemic toxicity was
      observed. At postmortem study, the ductus was patent, and histologic analysis
      showed variable intimal and medial destruction, endothelial regeneration, loss of
      elastic tissue and calcification. Adjacent pulmonary artery and aorta were
      normal. Based on the small sample size and the observed maximal effect size of
      70%, the power of the study is at most 40% to detect significant differences.
      CONCLUSIONS: To our knowledge, this is the first time that transvascular formalin
      infiltration of the ductus arteriosus wall has been applied successfully to
      maintain ductal patency in the newborn lamb. This method may provide a means of
      palliation for neonates with certain forms of congenital heart disease.

PMID- 8752821
TI  - Tumor necrosis factor-alpha is released from the isolated heart undergoing
      ischemia and reperfusion.
AB  - OBJECTIVES: The purpose of this study was to examine whether tumor necrosis
      factor-alpha (TNF-alpha) is released directly from the ischemic myocardium
      undergoing reperfusion. BACKGROUND: Tumor necrosis factor-alpha is a protein
      hormone produced by systemic leukocytes (primarily by activated macrophages). It
      has been implicated as a systemic mediator in the development of septic shock and
      other pathologic conditions. Serum TNF-alpha has also been detected in a variety
      of cardiac disease states and after myocardial ischemia-reperfusion injury.
      METHODS: Nine isolated rat hearts undergoing 30 min of perfusion, followed by
      warm cardioplegic arrest, 1 h of global ischemia and 30 min of reperfusion, were
      investigated using the modified Langendorff model. RESULTS: Significant amounts
      of TNF-alpha (752 +/- 212 pmol/ml) were detected in the effluent during the first
      minute of reperfusion. Tumor necrosis factor-alpha levels correlated with
      postischemic deterioration in peak systolic pressures (r = 0.7882, p = 0.012),
      dP/dt max (r = 0.6795, p = 0.044), time-pressure integral (r = 0.7661, p =
      0.0016) and postischemic creatine kinase levels (r = 0.8367, p = 0.005). The
      deterioration in coronary flow, however, was inversely correlated with TNF-alpha
      levels (r = -0.7581, p = 0.018). CONCLUSIONS: To our knowledge, this study is the
      first to suggest that the isolated rat myocardium synthesizes and releases TNF
      alpha in response to ischemia and reperfusion, which directly correlates with the
      postischemic deterioration in myocardial mechanical performance and the amount of
      cellular necrosis.

PMID- 8752822
TI  - Sequelae of Kawasaki disease in adolescents and young adults.
AB  - Kawasaki disease is an acute vasculitis of unknown etiology that predominantly
      affects children <5 years of age. Structural damage to the coronary arteries
      after the acute, self-limited illness is detected by echocardiography in
      approximately 25% of untreated patients. The long-term effects of the acute
      coronary arteritis are unknown. To define the spectrum of clinical disease in
      young adults that can be attributed to Kawasaki disease in childhood, we
      performed a retrospective survey of cases reported in the English and Japanese
      published data of adult coronary artery disease attributed to antecedent Kawasaki
      disease. The mean age at presentation with cardiac sequelae was 24.7 +/- 8.4
      years (range 12 to 39) for the 74 patients identified with presumed late sequelae
      of Kawasaki disease. Symptoms at the time of presentation with cardiac sequelae
      included chest pain/myocardial infarction (60.8%), arrhythmia (10.8%) and sudden
      death (16.2%). These symptoms were precipitated by exercise in 82% of patients.
      One-third of the patients in whom a chest radiograph was taken had ring
      calcification. Angiographic findings included coronary artery occlusion (66.1%).
      Extensive development of collateral vessels was reported in 44.1% of patients.
      Autopsy findings included coronary artery aneurysms (100%) and coronary artery
      occlusion (72.2%). The acute vasculitis of Kawasaki disease can result in
      coronary artery damage and rheologic changes predisposing to thrombus formation
      or progressive atherosclerotic changes that may remain clinically silent for many
      years. Coronary artery aneurysms and calcification on chest radiography were
      unusual features in this group of patients. A history of antecedent Kawasaki
      disease should be sought in all young adults who present with acute myocardial
      infarction or sudden death.

PMID- 8752823
TI  - The root of all evil.

PMID- 8752824
TI  - Recertification--its time has come.

PMID- 8752825
TI  - Tilt table testing for assessing syncope. American College of Cardiology.

PMID- 8752826
TI  - Effect of smoking status on response to thrombolytic therapy.

PMID- 8752827
TI  - Prognostic value of coronary calcification--I.

PMID- 8752828
TI  - Prognostic value of coronary calcification--II.

PMID- 8752829
TI  - Antibody penetration into the cells of mice and men.

PMID- 8752830
TI  - Psoriasin: a novel chemotactic protein.
AB  - Inflammatory skin disorders such as psoriasis show a preferential epidermal
      infiltration of neutrophils and T lymphocytes. This observation raises a question
      as to which factors determine the appearance and composition of leukocyte tissue
      infiltrations. Previously, we described a low molecular mass calcium-binding
      protein (psoriasin, molecular mass 11,457 Da, pI 6.77) belonging to the S1OO
      family that is highly upregulated in psoriatic keratinocytes and whose expression
      patterns implied a role in the inflammatory response. Here we report that human
      psoriasin is a potent and selective chemotactic inflammatory protein for CD4+ T
      lymphocytes and neutrophils at concentrations of about 10(-11) M. Psoriasin is
      not structurally related to the alpha or the beta chemokine subfamilies or to
      lymphotactin, a member of a newly described class of chemokines. Thus, we have
      observed a chemotactic protein outside the chemokine subfamilies that could be an
      important new inflammatory mediator.

PMID- 8752832
TI  - Human stratum corneum lipids have a distorted orthorhombic packing at the surface
      of cohesive failure.
AB  - The cohesive strength of the stratum corneum is determined by its unique
      molecular composition and structural architecture. Whereas the structure
      responsible for corneocyte cohesion has been visualized at the microscopic level,
      the structure of the intercellular domain has not been characterized at the
      molecular level. In this report, new insight into the molecular architecture of
      the stratum corneum has been provided by atomic force microscopy and x-ray
      photoelectron spectroscopy. The surface layer of human stratum corneum was
      stripped, yielding the characteristic polygonal corneocytes shown by scanning
      electron microscopy as well as low resolution atomic force microscopy. With
      atomic force microscopy, the resolution was increased to allow imaging of the
      molecular architecture of the stratum corneum. With the high resolution image, a
      repetitive pattern characteristic of lipids in an ordered state was visualized.
      The lattice appeared to be orthorhombic where the lattice distances were about
      5.5 and 9 angstroms, and the lattice angle was close to 90 degrees. The atomic
      composition of the superficial layers was 82% carbon, 16.5% oxygen, and 1.4%
      nitrogen as determined by x-ray photoelectron spectroscopy. The high nitrogen
      content compared to the calculated stratum corneum lipid composition and measured
      model lipid composition suggests that proteins were detected. In summary,
      although proteins are present, the fracture plane of the stratum corneum is
      largely composed of lipids that appear to have a distorted orthorhombic packing.

PMID- 8752831
TI  - Clouston syndrome (hidrotic ectodermal dysplasia) is not linked to keratin gene
      clusters on chromosomes 12 and 17.
AB  - Clouston syndrome is an hidrotic form of ectodermal dysplasia, inherited as an
      autosomal dominant trait with high penetrance. The main features of the disorder
      are alopecia, severe dystrophy of the nails, and palmoplantar hyperkeratosis. A
      molecular abnormality of keratin has long been hypothesized to be the basic
      defect in this disorder. We have performed linkage analyses between the disorder
      and markers close to the keratin gene clusters on chromosomes 12 and 17 and have
      excluded linkage to these candidate regions in three apparently unrelated
      families. In addition, linkage has been excluded to four other candidate regions
      including 1q2l, 17q23-qter, 18q2l, and 2Oql2. These data indicate that Clouston
      syndrome is not due to a defect in keratin or in a subset of keratin-associated
      proteins.

PMID- 8752834
TI  - Disease severity measures in a population of psoriasis patients: the symptoms of
      psoriasis correlate with self-administered psoriasis area severity index scores.
AB  - Because of the difficulty and expense of objectively measuring psoriasis
      severity, very little information exists on the severity of psoriasis in
      populations. We determined severity in a psoriasis patient population using the
      validated self-administered psoriasis area and severity index (SAPASI). This
      population consisted of 578 university dermatology clinic psoriasis patients, and
      data were analyzed from 317 (55%) questionnaire respondents. The majority of our
      sample was women (57%), and non-Caucasians represented a larger portion (8 %) in
      our sample compared with some previous studies. In our population, the reported
      frequencies of skin and joint symptoms were as follows: pruritus (95 %), skin
      burning (81 %), joint pain (69%), arthritis (51%), and psoriatic arthritis (20%).
      The SAPASI was significantly associated with severity of pruritus, burning, joint
      pain, and psoriatic arthritis. There was a significant negative correlation
      between the number of treatments employed and the SAPASI. This study provides
      results of a detailed measurement of the severity of psoriasis in a psoriasis
      patient population and relates this severity to population characteristics.

PMID- 8752833
TI  - Lanceolate hair (lah): a recessive mouse mutation with alopecia and abnormal
      hair.
AB  - A new autosomal recessive mutation of the house mouse developed generalized
      alopecia associated with breakage of abnormal hair shafts. This mutation, named
      'lanceolate hair' (symbol: lah), arose in a mutagenesis experiment using
      ethylnitrosourea. Hair shafts were short with a focal degeneration at the
      breakpoint characterized by a pronounced enlargement at the apex, resembling a
      lance head. Plucked hair fibers were 2.0 to 3.5 mm in length with a normal base,
      suggesting that there was a synchronized developmental defect. Histologic
      examination of anagen follicles revealed abnormal cornification of the matrix
      region with degeneration resulting in the focal hair shaft deformity. Catagen
      follicles showed pronounced follicular dystrophy but telogen follicles were
      almost normal. There was a marked, persistent thickening of the epidermis
      associated with a non-scarring, relatively non-inflammatory ichthyosiform
      dermatitis. These features are found in the Netherton's syndrome of the human,
      for which this mouse mutation may represent a model. The lah mutation has been
      localized to the centromeric end of mouse Chromosome 18.

PMID- 8752835
TI  - Genetic heterogeneity of familial primary cutaneous amyloidosis: lack of evidence
      for linkage with the chromosome 10 pericentromeric region in Chinese families.
AB  - Primary cutaneous amyloidosis is a relatively common skin disease in Southeast
      Asia, South America, and the Republic of China. Although most cases are sporadic,
      some patients have a family history, suggesting that genetic factors may play a
      role in its pathogenesis. Some patients with multiple endocrine neoplasia type 2A
      also have a clinical picture of primary cutaneous amyloidosis. It is thus
      suggested that the gene of familial primary cutaneous amyloidosis is linked to
      the pericentromeric region of chromosome 10, the location of the RET proto
      oncogene. We have carried out linkage analysis in seven families with cutaneous
      amyloidosis using four dinucleotide repeat markers from the RET region. Negative
      lod scores at all recombination frequencies were obtained. We thus conclude that
      there is no evidence for linkage between Chinese families with primary cutaneous
      amyloidosis and the pericentromeric region of chromosome 10. The distinct genetic
      basis, plus their apparent phenotypic differences in sex ratio, age of onset, and
      sites of cutaneous lesions, suggests that familial primary cutaneous amyloidosis
      includes clinical subtypes attributable to genetic heterogeneity.

PMID- 8752836
TI  - Th2 suppressor cells are more susceptible to sphingosine than Th1 cells in murine
      contact photosensitivity.
AB  - Murine contact photosensitivity (CPS) to 3,3',4',5-tetrachlorosalicylanilide
      (TCSA) is a cutaneous delayed-type hypersensitivity reaction in which both
      positive and negative regulatory pathways exist. The latter pathway is mediated
      by antigen-specific, CD4+ suppressor T cells (CPS-Ts) that are Th2 cells. We
      examined the effects of sphingosine and synthetic cell-permeable analogs of
      ceramide on the cellular kinetics of CPS-Ts and immune lymph node cells from TCSA
      photosensitized mice (CPS-LNC), along with other murine T-cell populations. The
      addition of sphingosine at 10 or 3 microM to in vitro cultures suppressed DNA
      synthesis of CPS-Ts and Th2 clones, including D10 cells and 24-2 cells, but not
      that of CPS-LNC or Thl clones, including 23-1-8 and 28-4 cells. This suggested
      that sphingosine exerts its inhibitory effects preferentially on the
      proliferation of Th2 cells. Although suppressing DNA synthesis, sphingosine
      augmented the production and mRNA expression of interleukin-4 (IL-4) and enhanced
      the expression of the IL-4 receptor in CPS-Ts. In addition, the ability of
      sphingosine to induce signal transduction of CPS-Ts was confirmed by elevation of
      the intracellular free Ca++ concentration. Because CPS-Ts exposed to sphingosine
      exhibited a lower G2M/G1 ratio than control, these seemingly ambivalent phenomena
      may be caused by retardation of the G1 to S phase progression, a cell-cycle
      dysregulation known to augment cytokine production. In contrast to sphingosine,
      cell-permeable ceramide did not affect the proliferation of these cells when
      stimulated with mitogen/antigen and did not augment IL-4 production by CPS-Ts.
      Our study suggests that sphingosine modifies the Th1/Th2 balance by
      preferentially affecting the cellular kinetics of Th2.

PMID- 8752837
TI  - The gene for multiple familial trichoepithelioma maps to chromosome 9p21.
AB  - Multiple familial trichoepithelioma (MFT) is an autosomal dominant skin disease
      characterized by the presence of many small tumors predominantly on the face. To
      map the causative gene, we performed linkage analysis with microsatellite markers
      in three American families. We found a significant linkage of a gene for MFT to
      chromosome 9p2l. The maximum combined lod score was 3.31 at D9S171 at theta = 0.
      The disease locus was defined to a 4-cM region between IFNA and D9S126. Because
      several tumor suppressor genes including p16 and p15 have been mapped to this
      region, the gene for MFT may also be a tumor suppressor.

PMID- 8752839
TI  - Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory
      effects in atopic dermatitis.
AB  - Increased cyclic AMP-phosphodiesterase activity in peripheral blood leukocytes is
      associated with the immune and inflammatory hyperreactivity that characterizes
      atopic dermatitis. Atopic phosphodiesterase has high sensitivity to a variety of
      enzyme inhibitors, suggesting an increased therapeutic advantage. The objective
      of this study was to use in vitro assays to identify a potent phosphodiesterase
      inhibitor and then to investigate its effectiveness in treating atopic
      dermatitis. Leukocyte enzyme activity was measured by radioenzyme assay, whereas
      prostaglandin E2 and interleukins 10 (IL-10) and 4 (IL-4) were measured in 24-h
      culture supernatants of mononuclear leukocytes by immunoassays. The effect of a
      topical phosphodiesterase inhibitor on atopic dermatitis lesional skin was
      assessed by double-blind, paired comparisons of active drug and placebo ointments
      applied to symmetrically involved sites over a 28-d period. Using in vitro,
      assays, we demonstrated the ability of selective high-potency phosphodiesterase
      inhibitors to reduce prostaglandin E2, IL-10, and IL-4 production in atopic
      mononuclear leukocyte cultures. We selected the Type 4 phosphodiesterase
      inhibitor, CP80,633, based on its inhibitory potency, for clinical testing by
      topical, bilateral paired comparisons in 20 patients with atopic dermatitis and
      demonstrated significant reductions of all inflammatory parameters.
      Phosphodiesterase inhibitors modulate several pathways contributing to the
      exaggerated immune and inflammatory responses, which characterize atopic
      dermatitis. This in vivo demonstration of anti-inflammatory efficacy may provide
      a useful alternative to the over-reliance on corticosteroid therapy in atopic
      disease.

PMID- 8752838
TI  - Localization and regulation of expression of the FAR-17A gene in the hamster
      flank organs.
AB  - A quantitative in situ hybridization study was carried out to determine the
      precise localization and androgen regulation of the flank organ regulated (FAR
      17A) mRNA expression in the different cellular components of the hamster flank
      organs. Although FAR-17A mRNA was highly expressed in the epithelial cells of the
      sebaceous glands, it was also found in the outer root sheath of the hair
      follicles and in melanocytes. The changes in FAR-17A mRNA levels, in the size of
      the flank organ and sebaceous gland areas as well as in the weight of the seminal
      vesicles and prostate, were compared following castration and after 5alpha
      dihydrotestosterone treatment. FAR-17A mRNA levels were already significantly
      decreased 1 d after castration, in parallel with a concomitant decrease in the
      number of labeled cells with the FAR-17A probe. A maximal decrease was found 7 d
      after castration. The other parameters were significantly reduced later. After 7
      d of treatment with dihydrotestosterone, all values returned to those found in
      intact animals. Similar stimulatory effects on these parameters were observed
      after treatment with the adrenal sex steroid precursor dehydroepiandrosterone.
      These data show that all of the components of the flank organs (sebaceous glands,
      hair follicles, and melanocytes) express the flank organ regulated (17A) type
      gene (FAR-17A) gene and that its expression is stimulated by treatment with
      either dihydrotestosterone or dehydroepiandrosterone. Moreover, FAR-17A mRNA
      levels respond to androgen stimulation more rapidly than the standard morphologic
      parameters, revealing that the FAR-17A gene could be a more sensitive and cell
      specific marker to study the mechanisms of androgen action in the skin.

PMID- 8752840
TI  - PUVA (5-methoxypsoralen plus UVA) enhances melanogenesis and modulates expression
      of melanogenic proteins in cultured melanocytes.
AB  - PUVA (combination of psoralens and ultraviolet A radiation) is a potent inducer
      of melanogenesis in normal human skin. The molecular mechanisms underlying this
      effect are poorly characterized. This study was undertaken to investigate the
      action of PUVA on melanogenesis in S91 murine melanoma cells and in cultured
      normal human melanocytes. Tyrosinase and DOPAchrome tautomerase (DCT) activities
      as well as melanin neosynthesis were measured in PUVA-treated pigment cells. To
      determine whether a correlation exists between PUVA-induced melanogenesis and
      expression of melanogenic enzymes, we analyzed the levels of tyrosinase, DCT, and
      tyrosinase-related protein-1 (TRP-1 or gp75) by western blotting in PUVA-treated
      cells. We demonstrate that UVA upregulates tyrosinase activity and melanin
      content with 5-methoxypsoralen at 1 microM. This phenomenon depends on the energy
      delivered during phototreatment. In both human and mouse cells, stimulation of
      melanogenesis correlated with an increase of the amount of tyrosinase. In PUVA
      treated S91 cells, tyrosinase mRNA was increased, but no stimulation of DCT
      activity occurred in these cells, in agreement with the unchanged amount of DCT
      protein in cell extracts. On the contrary, in melanocytes treated with PUVA, a
      decrease in DCT protein was observed. Finally, the amount of TRP-1 protein was
      not affected by PUVA in either S91 cells or melanocytes. These results show that
      melanogenesis induced by PUVA is related to an increase in expression of
      tyrosinase. In melanocytes, melanogenesis and DCT are negatively correlated,
      which suggests that PUVA favors the metabolic pathway of dark-eumelanins with
      high UV-protective properties. This study also suggests that PUVA regulates
      tyrosinase, DCT, and TRP-1 expression in a noncoordinate manner.

PMID- 8752841
TI  - The majority of autologous cytolytic T-lymphocyte clones derived from peripheral
      blood lymphocytes of a melanoma patient recognize an antigenic peptide derived
      from gene Pmel17/gp100.
AB  - Anti-melanoma cytolytic T-lymphocyte (CTL) clones were derived from peripheral
      blood lymphocytes of HLA-A2 melanoma patient LB265 after stimulation with the
      autologous tumor cell line LB265-MEL, which showed high expression of melanocyte
      lineage specific genes. Of 55 CTL clones, 46 recognized HLA-A2-restricted
      antigens. These 46 CTL clones were studied for their ability to specifically
      release tumor necrosis factor in the presence of COS cells cotransfected with the
      HLA-A2 gene and the cDNA of either tyrosinase, Melan-A/MART1, Pmel17/gpl00,
      gp75/TRP1, or MSH receptor. Six CTL clones recognized the Melan-A/MART1 antigen,
      whereas the remaining 40 CTL clones recognized a Pmel17/gp100 antigen. These 40
      anti-PmelI7/gpl00 CTL clones were all able to lyse T2 cells pulsed with the
      antigenic peptide YLEPGPVTA, as previously reported. The T-cell receptor beta
      chain hypervariable region was sequenced and found to be identical in the 15 CTL
      clones analyzed. Taken together, these data show a high frequency of Pmell7/gp100
      specific T cells in autologous antitumor CTL clones derived from peripheral blood
      of a melanoma patient.

PMID- 8752842
TI  - An active focus of high prevalence of fogo selvagem on an Amerindian reservation
      in Brazil. Cooperative Group on Fogo Selvagem Research.
AB  - Fogo Selvagem (FS) is an autoimmune disease characterized by subcorneal vesicles
      and antidesmoglein-1 autoantibodies. Previous epidemiologic data have linked the
      onset of FS to exposure to an environmental antigen(s). This investigation
      describes a unique human settlement with an extraordinarily high prevalence of
      FS. This community is made up of Amerindians belonging to the Terena tribe, which
      has settled on the Limao Verde reservation in the state of Mato Grosso do Sul in
      Brazil. Twenty-six well-characterized FS cases have been identified within a
      total population of 998, yielding a prevalence of 2.6%. Seventeen of the patients
      (65 %) were males, and over 50% were older than 30 y of age. The incidence of the
      disease shows temporal periodicity, i.e., years with several cases of FS
      alternating with years with no cases. Over one-half of the cases occurred in
      genetically related family members. Another Terena reservation, the
      Ipegue/Taunay, located 90 km west of the Limao Verde reservation, was also
      evaluated as a control group. This reservation, with a population of 2203, had no
      recorded cases of FS. Thus, the Limao Verde reservation represents a new focus of
      FS in which the disease exhibits temporal, geographic, and familial clustering.
      These results suggest that the environmental antigen or antigens precipitating FS
      are endemic to the Limao Verde reservation. This reservation appears to be an
      ideal population for carrying out sero-epidemiologic, genetic, and environmental
      studies aimed at disclosing the etiology of FS.

PMID- 8752843
TI  - The accumulation of protoporphyrin IX in plaque psoriasis after topical
      application of 5-aminolevulinic acid indicates a potential for superficial
      photodynamic therapy.
AB  - The success reported for the treatment of superficial skin carcinomas by
      photodynamic therapy with topical application of the photosensitizer precursor 5
      aminolevulinic acid has therapeutic implications for the treatment of other skin
      disorders. This paper describes the accumulation of the photosensitizing agent
      protoporphyrin IX in areas of plaque psoriasis by monitoring of the fluorescence
      emission induced by low-intensity laser excitation at 488 nm. We present results
      from 15 patients with a total of 42 plaques and show that the characteristic
      fluorescence emission of protoporphyrin IX increases in intensity within the 6-h
      period following application of 5-ami-nolevulinic acid, suggesting that there is
      a potential for superficial photodynamic therapy. The rate of increase and
      maximum intensity of fluorescence emission was not directly related to the
      applied quantity of the precursor. The variability of the fluorescence intensity
      was as great between plaques at different sites on the same patient as between
      different patients. Also, the effect of plaque occlusion following application
      appeared insignificant. Although there was only limited enhancement of emission
      from areas of skin surrounding the plaque, a significant buildup of sensitizer
      was detected after several days in some areas of psoriasis that received no
      application.

PMID- 8752844
TI  - Surface electrical capacitance as a noninvasive index of epidermal barrier in
      cultured skin substitutes in athymic mice.
AB  - Restoration of an epidermal barrier is a definitive requirement for wound
      closure. To determine formation of an epidermal barrier as a function of
      hydration of the stratum corneum, we measured surface electrical capacitance
      (SEC) of the epidermis in cultured skin substitutes (CSS) in vitro and after
      grafting to athymic mice. CSS were prepared from human keratinocytes and
      fibroblasts attached to collagen-glycosaminoglycan substrates. On culture days 3,
      7, 14, 17, and 21, SEC was measured in situ. CSS (n = 18; mean +/- SEM) showed a
      time-dependent decrease of SEC (picoFarads, "pF") from 4721 +/- 28 pF on day 3 to
      394 +/- 117 pF on day 14, and subsequent increase to 1677 +/- 325 pF on day 21.
      After 14-d incubation, parallel CSS samples (n = 5) or murine autografts (n = 5)
      were grafted orthotopically to athymic mice. After grafting, CSS showed decreases
      in SEC from 910 +/- 315 pF at 2 wk to 40 +/- 10 pF at 4 wk with no significant
      decreases thereafter. Control values for murine autograft were 870 +/- 245 pF at
      2 wk, and 87 +/- 30 pF at 4 wk. SEC values for native murine skin (n = 10) were
      91 +/- 18 pF, and for native human skin (n = 10) were 32 +/- 5 pF. The data
      demonstrate that SEC decreases with time in culture and that healed or intact
      skin has approximately 10- to 100-fold lower SEC than CSS in vitro. This
      noninvasive technique provides a quantitative index of epidermal barrier in CSS
      in vitro and demonstrates the development of functional epidermal barrier during
      healing of wounds treated with cultured skin substitutes.

PMID- 8752845
TI  - Platelet-activating factor biosynthesis induced by various stimuli in human HaCaT
      keratinocytes.
AB  - Platelet-activating factor (PAF) is a potent inflammatory mediator that is
      thought to play a role in cutaneous inflammation. These studies used mass
      spectrometry to examine the molecular species of PAF precursor
      glycerophosphocholine lipids (GPC) as well as the biosynthesis of PAF and other
      sn-2 acetyl-GPC in a human keratinocyte-derived cell line (HaCaT keratinocytes).
      Approximately 28% of HaCaT keratinocyte GPC consisted of 1-alkyl species, and the
      relative amounts of the sn-1 alkyl constituents of the PAF precursor 1-alkyl-2
      acyl-GPC were as follows: hexadecyl > octadecenyl > octadecyl. Ionophore (A23187)
      stimulated HaCaT keratinocytes synthesized both PAF (1-hexadecyl, 1-octadecenyl,
      and 1-octadecyl species) and less potent 1-acyl analogs (1-palmitoyl, 1-oleoyl,
      and 1-stearoyl species). PAF production was rapid and maximal by 10 min. The
      major species of sn-2acetyl-GPC at 2.5 min were 1-hexadecyl-2-acetyl-GPC (2.2
      ng/10(6) cells) and 1-palmitoyl-2-acetyl-GPC (2.4 ng/10(6) cells). HaCaT
      keratinocytes also synthesized PAF and 1-acyl PAF analogs when stimulated with
      the peptide growth factor endothelin-1 and the nonhydrolyzable PAF receptor
      agonist carbamyl-PAF. Both 1-hexadecyl-2- acetyl-GPC and 1-palmitoyl-2-acetyl-GPC
      stimulated intracellular calcium mobilization in HaCaT cells, indicating that
      these sn-2 acetyl-GPC act in autocrine fashion. These studies revealed that the
      human keratinocyte-derived cell line HaCaT can synthesize significant amounts of
      PAF and 1-acyl analogs in vitro from both nonspecific (A23187) and specific
      (endothelin-1, carbamyl-PAF) stimulation, suggesting a role for this inflammatory
      lipid mediator in keratinocyte pathophysiology.

PMID- 8752846
TI  - Spontaneous autoimmune skin lesions of MRL/n mice: autoimmune disease-prone
      genetic background in relation to Fas-defect MRL/1pr mice.
AB  - The autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mouse is characterized by the lpr
      mutation, which is a defect in the Fas antigen. Since Fas mediates apoptosis,
      this defect results in CD4-CD8- double negative T-cell proliferation, lupus
      nephritis, and macroscopic lupus erythematosus-like skin lesions. The control
      counterpart of MRL/lpr mouse is the MRL/Mp-+/+ (MRL/n) mouse, which lacks the lpr
      mutation and is almost normal during the first 6 mo of life. The lpr mutation,
      however, accelerates autoimmune phenomena in MRL/lpr mice. Thus, it is important
      to investigate autoimmune diseases like systemic lupus erythematosis in relation
      to the autoimmune disease-prone genetic background of MRL/n mice. We found that
      skin lesions in aged MRL/n mice had unique characteristics. The first
      characteristic is spontaneous occurrence, and the second is epidermal cell
      nuclear immunostaining with IgGs by direct immunofluorescence. The skin lesions
      in aged MRL/n mice showed milder inflammation than in MRL/lpr mice. A homogeneous
      pattern of epidermal cell nuclear staining was always associated with nuclear
      staining in kidney cells and also correlated with the in vitro binding of sera to
      keratinocytes cultured from newborn MRL/n mice. These results suggest that the
      skin lesions of aged MRL/n mice are a good model for certain types of cutaneous
      lupus erythematosus and also can provide new insights into the long-standing
      controversy whether epidermal cell nuclear staining occurs in vivo.

PMID- 8752847
TI  - Involucrin is a covalently crosslinked constituent of highly purified epidermal
      corneocytes: evidence for a common pattern of involucrin crosslinking in vivo and
      in vitro.
AB  - Involucrin (hINV) is an important structural component of the keratinocyte
      cornified envelope that is expressed early in the keratinocyte differentiation
      process and is thought to be a component of the initial envelope scaffolding. We
      have previously shown that cyanogen bromide (CNBr) cleavage of cornified
      envelopes isolated from cultured foreskin keratinocytes releases several discrete
      involucrin-immunoreactive peptides. In this study, we compare the pattern of
      release of immunoreactive hINV fragments from envelopes prepared from human
      breast skin and foreskin, and from spontaneous and induced envelopes prepared
      from cultured keratinocytes. We also identify one of the released products.
      Envelopes prepared from human breast skin or foreskin, or spontaneous or induced
      envelopes prepared from cultured cells differ significantly in structure. The
      envelopes isolated from epidermis appear to be structurally complete, whereas
      spontaneous envelopes appear less complete and the induced envelopes appear to be
      the least complete. In spite of these structural differences, CNBr cleavage
      releases an identical quartet of hINV-immunoreactive peptides migrating between
      68 and 81 kDa from each preparation. Immunoblots indicate that the quantity of
      hINV-immunoreactive material released per microg of envelope protein is as
      follows: induced > spontaneous > foreskin > breast skin. The fastest migrating
      peptide (68 kDa) comigrates with a peptide that is released after CNBr cleavage
      of bacterially produced-recombinant hINV. Amino-terminal amino acid sequencing of
      this peptide from recombinant hINV and from the cornified envelopes yields the
      sequence G-Q-L-K-H-L-E-Q-Q-E-G-Q-P-K-H. These results suggest that this fragment
      is the 275-amino acid segment of hINV beginning at G311 and extending to K585,
      and that this peptide is not crosslinked to another protein. These results
      indicate that a population of the envelope-associated hINV present in cultured
      and in vivo keratinocytes is crosslinked in the amino-terminal half. It is
      possible that this species represents an early intermediate in the involucrin
      crosslinking process.

PMID- 8752849
TI  - Targeted expression of insulin-like growth factor to human keratinocytes:
      modification of the autocrine control of keratinocyte proliferation.
AB  - Somatomedin C/insulin-like growth factor-I (IGF-I) is required for the
      proliferation of keratinocytes in vitro. In skin, the cells known to synthesize
      IGF-I are melanocytes and fibroblasts of the dermis. To investigate the role of
      IGF-I as a mediator of keratinocyte proliferation, we have used retroviral
      mediated gene transfer to introduce the gene encoding human IGF-I into diploid
      human keratinocytes, thus causing these cells to produce a growth factor they
      normally do not express. Modified cells synthesized and secreted significant
      levels of IGF-I (560 ng/10(7) cells/24 h) in vitro. Cells expressing IGF-I were
      no longer dependent on exogenously added IGF-I or insulin for their sustained
      growth in vitro under serum-free conditions. The growth of these cells did
      require added epidermal growth factor (EGF) and bovine pituitary extract. The
      addition of an antibody that neutralizes IGF-I inhibited cell growth, suggesting
      that IGF-I must be secreted by the cells to promote cell proliferation. To
      investigate the role of IGF-I in vivo, we grafted modified keratinocytes
      expressing IGF-I onto athymic mice. Grafts of epithelial sheets of modified cells
      formed a stratified epithelium comparable to control grafts of unmodified cells.
      When analyzed for keratin 16 expression and by quantitative staining for the
      nuclear proliferation antigen Ki-67, however, modified epithelia showed an
      increase in these markers of proliferation when compared with grafts of
      unmodified cells. This study demonstrates that genetic modification can be used
      to modify the autocrine control of keratinocyte proliferation. The de novo
      synthesis of IGF-I by keratinocytes could sustain keratinocytes growth in vitro
      and stimulate proliferation in vivo without significantly altering epidermal
      differentiation. These data further support the role of IGF-I as a paracrine
      mediator of epidermal proliferation and as a potential signal of mesenchymal
      epithelial interactions.

PMID- 8752848
TI  - Dermatophytes contain a novel lipid-like leukocyte activator.
AB  - In the early phase of dermatophytosis, neutrophils are regularly detected
      microscopically in the infected skin. Although neutrophil recruitment may at
      least in part occur indirectly by complement activation, we asked whether
      dermatophytes might release chemoattractants for neutrophils. We cultivated
      various strains of different dermatophytes and tested fungal extracts for the
      presence of neutrophil chemotactic activity. As a result, we detected neutrophil
      chemotactic activity only in diethylether extracts, but not in aqueous extracts.
      We purified this lipid-like leukocyte activator (LILA) to apparent homogeneity by
      reversed-phase high performance liquid chromatography and found that purified
      LILA does not show ultraviolet absorption at wavelengths > 210 nm. Biologic
      studies revealed that LILA is as effective as formyl-methionyl-leucyl
      phenylalanine in eliciting neutrophil chemotaxis, degranulation, and activation
      of the respiratory burst. Desensitization experiments in chemotaxis and
      degranulation with leukotriene B4, platelet-activating factor, or 5-oxo
      eicosanoids revealed that LILA does not cross-desensitize with any of these other
      lipid-like attractants and thus possibly acts via a distinct as yet postulated
      neutrophil receptor. It is hypothesized that LILA, similarly to formylated
      methionyl peptides in bacteria, represents a dermatophyte- and possibly fungus
      specific lipid compound that allows the host phagocytes to specifically recognize
      fungal infection. This system would be similar to the recognition of bacteria by
      phagocytes via N-formylated methionyl peptides, which represent a characteristic
      and unique system to identify bacteria.

PMID- 8752851
TI  - Successful treatment of chronic leg ulcers with epidermal equivalents generated
      from cultured autologous outer root sheath cells.
AB  - The outer root sheath cells of hair follicles can substitute for interfollicular
      epidermal keratinocytes, as during healing of skin wounds when these cells
      migrate onto the denuded area and contribute to epidermal regeneration. Using
      improved culture techniques, we generated epidermal equivalents from cultured
      outer root sheath cells of patients suffering from recalcitrant chronic leg
      ulcers, primarily of vascular origin. In such epidermal equivalents, tissue
      organization as well as immunolocalization of epidermal differentiation products
      (keratin 10, involucrin, filaggrin) and integrins were indistinguishable from
      normal epidermis. As determined by the number of bromodeoxyuridine-incorporating
      cells, the basal layer contained a large compartment of proliferative cells
      irrespective of donor age. FACS analysis of the outer root sheath cells, used to
      prepare the epidermal equivalents, disclosed a fraction of small cells with
      enhanced expression of beta1-integrin, a potential stem cell marker. in contrast
      to acute wounds, a major definitive take of grafted cultured autologous
      keratinocytes has not been convincingly demonstrated in chronic wounds. In a
      pilot study, grafting of epidermal equivalents generated in vitro from autologous
      outer root sheath cells on 11 ulcers in five patients resulted in a definitive
      take rate of about 80%, with subsequent complete healing within 2 to 3 wk of five
      out of seven ulcers grafted with densely arranged cultures. This improvement in
      the treatment of chronic leg ulcers with cultured autologous keratinocytes
      probably depends on the large compartment of proliferative cells as well as on a
      well-developed horny layer which prevents disintegration of the grafts. Practical
      advantages of the new technique are its noninvasiveness, the lack of need for
      surgical facilities or anesthesia, and a short immobilization period after
      grafting.

PMID- 8752850
TI  - Evaluation of human skin reconstituted from composite grafts of cultured
      keratinocytes and human acellular dermis transplanted to athymic mice.
AB  - This study evaluates the use of composite grafts of cultured human keratinocytes
      and de-epidermalized, acellular human dermis to close full-thickness wounds in
      athymic mice. Grafts were transplanted onto athymic mice and studied up to 8 wk.
      Graft take was excellent, with no instances of infection or graft loss. By 1 wk,
      the human keratinocytes had formed a stratified epidermis that was fused with
      mouse epithelium, and by 8 wk the grafts resembled human skin and could be freely
      moved over the mouse dorsum. Immunostaining for keratins 10 and 16 and for
      involucrin revealed an initial pattern of epithelial immaturity, which by 8 wk
      had normalized to that of mature unwounded epithelium. Mouse fibroblasts began to
      infiltrate the acellular dermis as early as 1 wk. By 8 wk fibroblasts had
      completely repopulated the dermis, and blood vessels were evident in the most
      superficial papillary projections. Dermal elements, such as rete ridges and
      elastin fibers, which were present in the starting dermis, persisted for the
      duration of the experiment. Grafts using keratinocytes from dark-skinned donors
      as opposed to light-skin donors had foci of pigmentation as early as 1 wk that
      progressed to homogenous pigmentation of the graft by 6 wk. These results
      indicate that melanocytes that persist in vitro are able to resume normal
      function in vivo. Our study demonstrates that composite grafts of cultured
      keratinocytes combined with acellular dermis are a useful approach for the
      closure of full-thickness wounds.

PMID- 8752852
TI  - Identification of a 168-kDa mucosal antigen in a subset of patients with
      cicatricial pemphigoid.
AB  - This study describes the presence of antibodies in sera from patients with
      cicatricial pemphigoid specific for a 168-kDa antigen expressed by buccal mucosa.
      Six cicatricial pemphigoid sera unreactive, with epidermal or dermal proteins in
      immunoblot assay were tested on mucosal protein extracts. Four of these sera
      labeled a mucosal 168-kDa antigen (M168) under reducing conditions. An additional
      cicatricial pemphigoid serum with circulating antibodies to 180-kDa bullous
      pemphigoid antigen (BPAg2) also labeled M168. None of these cicatricial
      pemphigoid sera reacted with the alpha, beta, or gamma subunits of laminin-5.
      Nitrocellulose elution studies showed that the M168 antigen is a basement
      membrane antigen and labeled the epidermal side of salt-split skin.
      Immunoaffinity-purified anti-M168 antibodies did not bind to the 230-kDa bullous
      pemphigoid antigen (BPAg1) or to the 180-kDa BPAg2. None of the control sera from
      healthy individuals or from bullous pemphigoid, pemphigus vulgaris, or pemphigus
      foliaceus patients reacted with Ml68. This study demonstrates the specificity of
      some cicatricial pemphigoid sera against a 168-kDa antigen that is different from
      the laminin-5 subunits and shares no epitopes with the antigens of bullous
      pemphigoid (BPAg1, BPAg2) or the epidermolysis bullosa acquisita.

PMID- 8752853
TI  - Genetic heterogeneity in lamellar ichthyosis.

PMID- 8752854
TI  - HIV-1 transmission to lymphoid cells from epidermal cell cultures derived from
      skin biopsies of AIDS patients.

PMID- 8752855
TI  - Advice for preventing sexual misconduct charges.

PMID- 8752856
TI  - Brian McCardel, MD.

PMID- 8752857
TI  - CME today looks to the future.

PMID- 8752858
TI  - Assisted suicide revisited.

PMID- 8752859
TI  - [Management of MRSA-harboring patients: focused on mupirocin].

PMID- 8752860
TI  - [Susceptibilities of bacteria isolated from patients with respiratory infectious
      diseases to antibiotics (1994)].
AB  - Bacteria isolated from lower respiratory tract infections were collected in
      cooperation with institutions located throughout Japan, since 1981. IKEMOTO et
      al. have been investigating susceptibilities of these isolates to various
      antibacterial agents and antibiotics, and characteristics of the patients and
      isolates from them each year. Results obtained from these investigations are
      discussed. In 23 institutions around the entire Japan, 492 strains of presumably
      etiological bacteria were isolated mainly from the sputum of 421 patients with
      lower respiratory tract infections from October 1994 to September 1995. MICs of
      various antibacterial agents and antibiotics were determined against 70 strains
      of Staphylococcus aureus, 101 strains of Streptococcus pneumoniae, 92 strains of
      Haemophilus influenzae, 61 strains of Pseudomonas aeruginosa (non-mucoid
      strains), 25 strains of Pseudomonas aeruginosa (mucoid strains), 48 strains of
      Moraxella subgenus Branhamella catarrhalis, 14 strains of Klebsiella pneumoniae
      etc., and the drug susceptibilities of these strains were assessed except for
      those strains that died during transportation. 1. S. aureus. S. aureus strains
      for which MICs of oxacillin were higher than 4 micrograms/ml (methicillin
      resistant S. aureus) accounted for 51.4%, but the frequency of the drug resistant
      bacteria decreased comparing to the previous year's 56.0%. Vancomycin showed the
      highest activity against S. aureus with MIC80 of 0.5 microgram/ml. 2. S.
      pneumoniae. Most of the drugs tested showed potent activities against S.
      pneumoniae. Imipenem of carbapenems showed the most potent activity with MIC80
      was 0.063 microgram/ml. Erythromycin and clindamycin showed low activities with
      MIC80s > or = 256 micrograms/ml. Among these strains, however, 46.5% and 68.3% of
      strains, were quite sensitive toward these agents, respectively, with MICs of
      0.063 microgram/ml. 3. H. influenzae. The activities of all drugs were potent
      against H. influenzae tested. Cefmenoxime a cephem, showed the most potent
      activity, the MICs of this drug against all of the 92 strains were 0.063
      microgram/ml. Ofloxacin also showed a potent activity, and inhibited about 96% of
      strains with MIC of 0.063 microgram/ml. 4. P. aeruginosa (mucoid strains).
      Tobramycin showed the most potent activity against P. aeruginosa (mucoid strains)
      with MIC80 of 0.5 microgram/ml. Gentamicin, arbekacin and ciprofloxacin showed
      next potent activities, and their MIC80s were 2 micrograms/ml. 5. P. aeruginosa
      (non-mucoid strains). Tobramycin showed the most potent activity against P.
      aeruginosa (non-mucoid strains) with MIC80 of 2 micrograms/ml. Comparing to the
      activities against P. aeruginosa (mucoid strains), the activities of all the
      drugs tested were lower against P. aeruginosa (non-mucoid strains). 6. K.
      pneumoniae. Carumonam showed the most potent activity against K. pneumoniae with
      MIC80 of 0.063 microgram/ml. Cefozopran showed the next most potent activity with
      MIC80 of 0.125 microgram/ml. Ampicillin and cephems except cefpodoxime,
      cefozopran and cefditoren showed low activities and their MIC80s were > or = 16
      micrograms/ml, and their MICs were all higher than > or = 4 micrograms/ml. 7. M.
      (B.) catarrhalis. Imipenem and ofloxacin showed the most potent activities
      against M. (B.) catarrhalis, their MIC80s were 0.063 microgram/ml. Erythromycin
      and minocycline showed the next highest activities with their MIC80s at 0.25
      microgram/ml. Also, we investigated year to year changes in the background of
      patients, the respiratory infectious diseases, and the etiology of bacteria.
      Patients characteristics, in this period of investigation showed varieties of
      infectious diseases found in patients in a high age bracket, and the patients
      over age 60 accounted for 62.0% of all the cases. Different lower respiratory
      tract infectious were distributed as follows: chronic bronchitis and bacterial
      pneumonia accounted for the greatest number of cases with 35.6%, 27.1%,
      respectively, followed by

PMID- 8752861
TI  - [Isolation rate of E. coli from surgical infections and their susceptibilities].
AB  - Escherichia coli isolated from surgical infections during the period from July
      1983 to June 1995 were investigated in a multicenter study involving 19 hospitals
      in Japan, and the following results were obtained. 1. Although the isolation rate
      of E. coli was not high from postoperative infections, it was most frequently
      isolated from primary infections throughout the study period. E. coli, Klebsiella
      spp. and anaerobic bacteria were predominant from fresh infections. From the
      cases that had previous antibiotics treatment, Enterococcus spp. were the most
      predominant isolates followed by MRSA and Pseudomonas spp. in this order. 2.
      Against E. coli, cefozopran, carumonam and aztreonam had the strongest activity,
      followed by cefmenoxime, imipenem, latamoxef, gentamicin and ofloxacin. Recently,
      we have noticed that antibiotic resistant E. coli strains particularly against
      cefazolin are increasing year by year.

PMID- 8752862
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from patients with urinary tract infections (1994). I.
      Susceptibility distribution].
AB  - The frequencies of isolation and susceptibilities to antimicrobial agents were
      investigated on 567 bacterial strains isolated from patients with urinary tract
      infections in 10 hospitals during the period of June 1994 to May 1995. Of the
      above total bacterial isolates, Gram-positive bacteria accounted for 26.8% and a
      majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for
      73.2% and most of them were Escherichia coli. 1. Enterococcus faecalis.
      Ampicillin (ABPC) and imipenem (IPM) showed the highest activities against E.
      faecalis isolated from patients with urinary tract infections. The MIC90s of them
      were 1 microgram/ml. Vancomycin (VCM) was also active with the MIC90 of 2
      micrograms/ml. Piperacillin (PIPC) and biapenem (BIPM) were also active with the
      MIC90s of 4 micrograms/ml and 8 micrograms/ml, respectively. The others were not
      so active with the MIC90s of 16 micrograms/ml or above. 2. Staphylococcus aureus
      including MRSA. VCM showed the highest activities against S. aureus isolated from
      patients with urinary tract infections. Its MIC90 was 1 microgram/ml against both
      S. aureus and MRSA. Arbekacin (ABK) was also active with the MIC90 of 2
      micrograms/ml. The others except minocycline (MINO) were not so active with the
      MIC90s of 64 micrograms/ml or above. 3. Staphylococcus epidermidis. MINO showed
      the strongest activity against S. epidermidis isolated from patients with urinary
      tract infections. Its MIC90 was 0.25 microgram/ml. ABK was also active with the
      MIC90 of 1 microgram/ml. Cephems were active with the MIC90s of 2 approximately
      16 micrograms/ml, but penicillins and quinolones were not so active with the
      MIC90s and 64 approximately 128 micrograms/ml. 4. Citrobacter freundii.
      Gentamicin (GM) showed the highest activities against C. freundii isolated from
      patients with urinary tract infections. Its MIC90 was 1 microgram/ml. IPM was
      also active with the MIC90 of 2 micrograms/ml. Cefpirome (CPR) and cefozopran
      (CZOP) were also active with the MIC90s of 4 micrograms/ml and 8 micrograms/ml.
      The others were not so active with the MIC90s of 32 micrograms/ml or above. 5.
      Enterobacter cloacae. IPM showed the highest activities against E. cloacae. Its
      MIC90 was 0.5 microgram/ml. GM and amikacin (AMK), ciprofloxacin (CPFX) and
      tosulfloxacin (TFLX) were also active with the MIC90s of 4 micrograms/ml.
      Penicillins and cephems except latamoxef (LMOX), cefmenoxime (CMX), CPR and CZOP
      showed lower activities with the MIC90s of 256 micrograms/ml or above. 6.
      Escherichia coli. Most of antimicrobial agents were active against E. coli. CPR,
      CZOP, IPM, carumonam (CRMN), CPFX and TFLX showed the highest activities against
      E. coli. The MIC90s of them were 0.125 microgram/ml or below. Cefotiam (CTM),
      flomoxef (FMOX) CMX, ceftazidime (CAZ), and LMOX were also active with the MIC90s
      of 0.25 microgram/ml. Penicillins were not so active with the MIC90s of 128
      micrograms/ml or above. 7. Klebsiella pneumoniae. CRMN showed the highest
      activities against K. pneumoniae. Its MIC90 was < or = 0.125 microgram/ml. CZOP
      was also active with the MIC90 of 0.25 microgram/ml. Penicillins were not so
      active with the MIC90s of 128 micrograms/ml or above. 8. Proteus mirabilis. P.
      mirabilis was susceptible to a majority of drugs. CMX, CAZ, LMOX, CRP,
      cefpodoxime (CPDX), CRMN, CPFX and TFLX showed the highest activities against P.
      mirabilis isolated from patients with urinary tract infections. The MIC90s of
      them were 0.125 microgram/ml or below. MINO was not so active with the MIC90 of
      128 micrograms/ml. 9. Pseudomonas aeruginosa. Most of the agents were not so
      active against P. aeruginosa. IPM showed MIC90 of 8 micrograms/ml. The others
      were not so active with the MIC90s of 16 micrograms/ml or above. CPFX showed
      MIC50 of 0.5 microgram/ml.

PMID- 8752863
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from patients with urinary tract infections (1994). II.
      Background of patients].
AB  - Clinical background was investigated on 628 bacterial strains isolated from
      patients with urinary tract infections (UTIs) in 10 hospitals during period from
      June, 1994 to May, 1995. 1. Distributions of sex, age and urinary tract
      infections Among over sixties males, the majority was taken by complicated
      urinary tract infections. Among females, the uncomplicated urinary tract
      infections was most frequent without a relation of age. As for over 40 females,
      the increase of complicated UTI was admitted. 2. Distribution of sex, age and
      pathogens isolated from UTIs In uncomplicated UTIs, Escherichia coli was most
      frequently isolated without a relation of age, and next Enterococcus faecalis and
      CNS. In complicated UTIs without indwelling catheter, E. coli, Pseudomonas
      aeruginosa and E. faecalis were isolated the most frequent. In complicated UTIs
      with indwelling catheter, P. aeruginosa was most frequently isolated, and next E.
      faecalis and Staphylococcus aureus. 3. Administration of antimicrobial agents and
      pathogens isolated from UTIs In uncomplicated UTIs, pathogens, after
      administration of antibiotics, isolated from patients have obviously decreased
      from 216 to 32 isolates. And also, pathogens of complicated UTIs without
      indwelling catheter, have decreased from 127 to 50 isolates. However, in
      complicated UTIs with indwelling catheter, pathogens after or before
      administration of antibiotics, were not revealed an obvious change. 4. Pathogens
      and UTIs with or without factor and operation In uncomplicated UTIs with or
      without factor and operation, E. coli was mainly detected. In complicated UTIs
      without indwelling catheter and with factor and operation E. faecalis was mainly
      detected, and next E. coli, S. aureus and P. aeruginosa. Without factor and
      operation, E. coli was mainly detected. In complicated UTIs with indwelling
      catheter and with factor and operation, P. aeruginosa, E. faecalis and S. aureus
      were mainly detected at 23.5%, 15.0%, 15.0%, respectively. Without factor and
      operation, Proteus spp. 22%, and next E. faecalis and P. aeruginosa 10% and 12%,
      were detected, respectively. The distribution of pathogens, in the case of
      Proteus spp. and P. aeruginosa has been obviously varied by the influence of
      factor and operation.

PMID- 8752864
TI  - [Antibacterial activities of combination uses of isepamicin and beta-lactams in
      vitro against clinically isolated strains. Part 3. The results against
      Pseudomonas aeruginosa].
AB  - We investigated antibacterial activities of combination uses of isepamicin (ISP)
      and beta-lactams in vitro against Pseudomonas aeruginosa, and the following
      conclusions were obtained. 1. ISP + piperacillin, ISP + ceftazidime, ISP +
      aztreonam, ISP + imipenem and ISP + panipenem against P. aeruginosa showed strong
      combined effects. 2. The minimum inhibitory concentrations (MICs) of these
      combinations were low and dependent on concentrations of ISP. And strong
      antibacterial activities were observed at ISP concentrations of sub-MIC levels.
      These results were similar to the results of previous reports, parts 1 and 2. 3.
      Concentrations of ISP sufficient to lower MIC90 values when by combined with beta
      lactam agents were 4 approximately 8 micrograms/ml. These effects made it
      possible to lower the ISP dose to 400 mg at a single dose and the enhancement of
      activities by combinations resulted in strong antibacterial activities against
      multiple drug resistant stains at sub-MIC levels of ISP. Strong antibacterial
      activities were also obtained against beta-lactams-resistant strains of ISP
      susceptible strains when ISP was combined with beta-lactam agents. 4. All results
      reported in parts 1 approximately 3 indicated that no antagonisms were produced
      by combining ISP + penicillins, ISP + cephems, ISP + monobactams and ISP +
      carbapenems against Staphylococcus aureus, Enterobacteriaceae and P. aeruginosa.
      These combinations showed strong antibacterial activities that were enhanced
      synergistically with wider spectra.

PMID- 8752865
TI  - [Transferability of cefozopran to cerebrospinal fluid in rabbits with meningitis
      caused by Staphylococcus aureus].
AB  - The transferability of cefozopran (CZOP) to cerebrospinal fluid (CSF) was studied
      employing rabbits with experimental meningitis caused by Staphylococcus aureus.
      The mean plasma concentration was 293 +/- 17.6 micrograms/ml at 15 minutes after
      intravenous administration of CZOP at a dose level of 100 mg/kg. The mean
      concentration in CSF reached its maximum, 16.5 +/- 2.74 micrograms/ml at 60
      minutes after administration. Pharmacokinetic parameters calculated from these
      values were as follows: Cmax (CSF/plasma) 5.72%, AUC (CSF/plasma) 6.61% between
      15 and 60 minutes, 9.38% between 15 and 120 minutes and 11.2% between 15 and 180
      minutes, T 1/2 for CZOP in CSF: 138 minutes, T 1/2 (CSF/plasma): 2.81. In
      comparison to those of beta-lactams that were obtained in the same way, the
      transferability of CZOP to CSF was moderate but concentration in CSF was high,
      hence, in consideration of the antimicrobial potency against the main pathogens
      of meningitis, it appears worthwhile of running clinical trials for CZOP.

PMID- 8752866
TI  - Variations in glutelin and high molecular weight endosperm proteins among
      subspecies of rice (Oryza sativa L.) detected by two-dimensional gel
      electrophoresis.
AB  - Variations in endosperm polypeptides among 16 cultivars of rice were analyzed by
      two-dimensional gel electrophoresis. One glutelin alpha-subunit (alpha 8) with a
      molecular mass of 32.5 kDa was exclusively present in indica cultivars. By
      contrast, the glutelin alpha 3 subunit, with a molecular mass of 32 kDa, was
      present only in japonica and javanica cultivars. Glutelin alpha-subunits alpha 5a
      and alpha 5b, which have a molecular mass of 32 kDa and slightly different
      isoelectric points, differed among rice subspecies, i.e. the former was detected
      in japonica cultivars and the latter was detected in indica cultivars. Internal
      amino acid sequences of the indica-specific glutelin alpha-subunits alpha 5b and
      alpha 8, were analyzed with a gas-phase protein sequencer. Of 46 amino acid
      residues determined, only two residues differed, and they corresponded with the
      sequences deduced from type I and type II cDNAs of glutelin subfamily A,
      respectively. Nine polypeptides of higher molecular mass (35-90 kDa) also
      differed. In particular, two of these polypeptides designated B and C which were
      identical to Wx proteins with molecular masses of 58 kDa were strongly expressed
      in indica endosperms, but only weakly expressed in japonica and javanica. F1
      seeds obtained from a cross between japonica and indica cultivars showed an
      intermediate intensity of Wx proteins and contained all nine glutelin alpha
      subunits including both the japonica and indica types. In this experiment, Wx
      proteins designated B and C and glutelin alpha-subunits could be used to identify
      differences between japonica and indica cultivars.

PMID- 8752867
TI  - The secondary structure and phylogenetic relationship deduced from complete
      nucleotide sequence of mitochondrial small subunit rRNA in yeast Hansenula
      wingei.
AB  - We have accomplished the nucleotide sequence of the 1537 bp mitochondrial gene
      coding for small subunit (SSU) rRNA of yeast Hansenula wingei, and also
      determined the 5'- and 3'-termini by S1 nuclease mapping. Eight universally
      conserved (U) elements of the SSU rRNA were identified. Comparison of U regions
      among five fungal mitochondrial SSU rRNA shows the striking similarity between H.
      wingei and Saccharomyces cerevisiae. The construction of the secondary structure
      revealed a core structure similar to the counterpart of Escherichia coli 16S
      rRNA. The secondary structure also enabled us the specify seven variable (V)
      regions differing from those of other mitochondrial SSU rRNAs in size, sequence
      and possible secondary structure. Molecular phylogenetic evaluation based on U
      regions of five fungi indicates that mitochondria of H. wingei and S. cerevisiae
      diverged from the same lineage. This suggests that the evolution of mitochondria
      encoded genes does not directly correlate with the alteration of mitochondrial
      genetic system: genome size, gene organization and codon usage.

PMID- 8752868
TI  - A ubiquitin-protein ligase (E3) mutation of Saccharomyces cerevisiae suppressed
      by co-overexpression of two ubiquitin-specific processing proteases.
AB  - To isolate mutations related to the ubiquitin system, I constructed a plasmid
      carrying the YUH1 and UBP1 genes (genes of ubiquitin-specific processing
      proteases) whose expressions were under the control of the galactose-inducible
      GAL1-GAL10 promoter. Cells of a strain carrying the plasmid were mutagenized with
      ethyl methanesulfonate. One mutant, which showed galactose-dependent growth at a
      high temperature (37 degrees C), was isolated from about 380,000 mutagenized
      colonies. The mutation responsible for galactose-dependent growth at 37 degrees C
      was a single nuclear recessive mutation designated as uby1-1. UBP1 and YUH1 as
      well as the GAL1-GAL10 promoter are required to suppress uby1-1. At the
      restrictive temperature, a uby1-1 mutant did not arrest at a specific phase of
      the cell cycle, but still lost viability. Even at the permissive temperature (30
      degrees C), the uby1-1 mutant grew somewhat slowly and showed pleiotropic
      phenotypes including hypersensitivity to stresses such as cadmium and canavanine,
      and sporulation defects. The genomic DNA fragments in a single-copy plasmid which
      complemented uby1-1 were isolated. Chromosomal mapping, sequencing and subcloning
      analyses indicated that the gene complementing uby1-1 is RSP5, which encodes a
      ubiquitin-protein ligase (E3) homologous to E6-AP (E6 associated protein).
      Deletion, complementation and linkage analyses revealed that UBY1 and RSP5 are
      the same gene. Therefore, the E3 protein encoded by RSP5 (UBY1) is required for
      vegetative growth, sporulation and stress response. The present procedure using
      suppression by co-overexpression of two cloned genes will be useful to isolate
      mutations of related genes and to analyze biochemical pathways and gene
      interactions.

PMID- 8752870
TI  - New DNA data collected and processed at DNA Data Bank of Japan.

PMID- 8752869
TI  - RNA editing of transcripts of the gene for apocytochrome b (cob) in rice
      mitochondria.
AB  - RNA editing was examined in rice mitochondrial apocytochrome b (cob) transcripts.
      Nineteen C-U conversions were found, and most of them changed the polypeptide
      sequence encoded by genomic DNA sequence. Evidence for partial and excess editing
      was also found.

PMID- 8752871
TI  - [Functional mapping of the brain in a patient before neurological surgery by
      superposition of activation SPECT and MR images].

PMID- 8752872
TI  - [Clinical study of intraspinal neoplasms in children].
AB  - The authors report a series of 10 children under 15 years of age with primary
      intraspinal neoplasm who underwent surgical resection from 1981 to 1994. The
      tumors consisted of 4 intramedullary tumors (myxopapillary ependymoma, pilocytic
      astrocytoma, subpial liporna, cavernous angioma), 2 intradural extramedullary
      tumors (2 neurinomas), and 4 extradural tumors (ganglioneuroma, chordoma,
      osteochondroma, rhabdomyosarcoma). The initial symptoms in these patients were
      gait disturbance (50%), weakness of lower extremities (50%), pain (40%), weakness
      of upper extremities (10%), and tetraparesis (10%). The neurological findings on
      admission in these patients revealed motor paresis (90%), sensory disturbance
      (60%), abnormality of deep tendon reflex (60%), pathological reflex (30%),
      neurogenic bladder (30%), and Lasegue's sign (10%). All patients were treated
      surgically; laminectoy was performed in 8 patients, laminoplasty in one patient,
      and transoral approach in one patient. Five patients (50%) underwent a grossly
      total resection, 3 (30%) had a subtotal resection, and 2 (20%) had a partial
      resection. Mean follow-up period was 5.6 years. One (10%) patient died due to
      recurrence and dissemination of the tumor at eight months after surgery in a case
      of rhabdomyosarcoma. 9 (90%) have had no recurrent tumor and have improved
      neurologically. In 4 patients (40%) spinal deformity developed, and 2 patients
      required operative treatment for the spinal deformity. We emphasized the
      advantage of laminoplasty to prevent postoperative spinal deformity in children.

PMID- 8752873
TI  - [The operation for malignant tumors in the frontal skull base: combined
      transbasal & transfacial approach].
AB  - The authors have previously reported on an extensive transbasal approach, through
      which a supraorbital bar is osteotomized. This operative technique has been
      applied by the authors not merely to benign but also to malignant tumors in the
      frontal skull base. However, in the operation for malignant tumors of the frontal
      base, it is important to resect en-bloc the tumors and surrounding tissues, such
      as dura of the skull base and the orbital contents. The authors describe the
      operative mode of the combined transbasal & transfacial approach and its good
      results in 19 cases with malignant tumors in the frontal skull base, and 3 types
      of en-bloc resection in this operative approach (from type A to C) are
      introduced. Type A of en-bloc resection in the combined transbasal & transfacial
      approach was performed in 11 cases with the tumors invading the ethmoid sinuses.
      Type B was performed in 4 cases with tumors extending to the orbit. Type C was
      performed in 4 cases with tumors extending to the orbit and the maxillary sinuses
      on the affected side. These operative modes are useful in skull base surgery.

PMID- 8752874
TI  - [Acute epidural hematoma of posterior fossa: comparative analysis between 20
      cases in adults and 10 cases in children].
AB  - A comparative study of the clinical features was made among 30 patients, 10
      children (less than 14) and 20 adults (older than 15) with traumatic acute
      epidural hematoma of the posterior fossa (PFEDH). The characteristic findings in
      both groups were as follows: 1) PFEDH accounted for 15% of 200 epidural hematoma
      cases. Incidence of PFEDH was 23.3% (10/43) in children and 12.7% (20/157) in
      adults. Thus, PFEDH is more common in children than in adults. 2) In seven out of
      10 children, PFEDH was confined to the posterior fossa but in the other three
      children, PFEDH extended to the supratentorial area. On the other hand, in all
      the adult cases PFEDH extended over the supratentorial space. 3) Hematoma density
      was high in 5 out of 10 children and 18 in out of 20 adults. Mixed (including
      low) density occurred at a higher rate in children (50%) than in adults (10%). 4)
      Brain contusion associated with PFEDH was found by CT scan in 12 adult cases and
      one child case. Subarachnoid hemorrhage was found by CT scan in 4 adult cases.
      Subdural effusion was found by CT scan in 1 adult case. Thus, intracranial
      complications associated with PFEDH occurred in a significantly higher number in
      adults than in children. 5) 20 cases (4 children, 16 adults) of 30 underwent
      surgery, and 10 cases (6 adults, 4 children) were given conservative treatment.
      Results (GOS); GR was observed in 22 cases (in all 10 children and in 12 adults),
      and MD in 8 cases. There were no SD, VS or cases ending in death.

PMID- 8752875
TI  - [Postoperative olfactory dysfunction in interhemispheric approach for ruptured
      anterior communicating artery aneurysms].
AB  - Between 1969 and 1994 we treated 450 patients with ruptured anterior
      communicating artery aneurysms, of which 434 cases (96.4%) were operated on via
      the interhemispheric approach (IH), namely, until 1979 mainly, via bifrontal
      craniotomy, subfrontal and interhemispheric approach (SIH) and, since 1979, via
      posterior interhemispheric approach (PIH). Postoperative olfactory dysfunction is
      one of the main disadvantages of IH. The mechanisms and the incidence of this
      disadvantage were studied in both approaches. The causes of postoperative anosmia
      in SIH were as follows: sectioning of olfactory tracts intentionally or not,
      avulsion of olfactory bulbs and probability of ischemic or minor mechanical
      insults to olfactory tracts. However, these matters rarely occur in PIH because
      of little exposure of olfactory nerves. The mechanisms of postoperative anosmia
      in PIH were considered to be as follows: sinking of frontal lobes due to
      excessive drainage of cerebrospinal fluid and over-retraction of frontal lobes.
      The incidence of postoperative anosmia decreased from 27.0% via SIH to 5.5% via
      PIH.

PMID- 8752876
TI  - [Recanalization of dural sinus occlusion following the disappearance of dural
      arteriovenous fistula: report of a case].
AB  - A 73-year-old female was admitted to our hospital because of disturbed
      consciousness and left-sided motor weakness. Computed tomographic scans
      demonstrated a hemorrhagic infarction in the right parietal region. Right carotid
      angiograms showed both the posterior portion of the superior sagittal sinus (SSS)
      and the entire left transverse sinus simultaneously occluded. Left carotid
      angiograms revealed an enlarged occipital artery, which had direct communications
      to the left sigmoid sinus and the superior petrosal sinus. These findings were
      consistent with dural arteriovenous fistula (D-AVF). The laboratory examinations
      yieled normal results. The patient was managed conservatively with glyceol and
      anticonvulsants for four weeks and eventually recovered with complete resolution
      of hemiparesis. Follow-up angiography carried out 6 weeks later showed the SSS,
      partially stenotic, but recanalized with no evidence of venous congestion. The D
      AVF still remained opacified, but there was a marked reduction in retrograde flow
      to the sigmoid sinus. Further repeated angiograms obtained at 10 months after the
      onset confirmed complete recanalization of the SSS and disappearance of the D
      AVF. From the timing of the angiographies, we considered that the sinus occlusion
      was caused by the high arterial flow to the fistula and its disappearance made
      recanalization of SSS possible.

PMID- 8752877
TI  - [Saccular aneurysm associated with fenestration of the distal segment of basilar
      artery].
AB  - A 32-year-old man who presented with subarachnoid hemorrhage was found to have a
      saccular aneurysm arising from the proximal end of the fenestration formed at the
      distal third of basilar artery. The aneurysm dome was directed anteriorly and
      measured 3mm in diameter. It was successfully clipped via subtemporal
      transtentorial approach and the patient returned to his previous job. Basilar
      artery fenestration is angiographically found in 0.23-0.6%. The fenestration is
      most frequently located in the proximal basilar trunk close to the vertebro
      basilar junction. In this report a rare case with an aneurysm associated with
      fenestration in the distal part of the basilar artery will be presented.

PMID- 8752879
TI  - [Intraorbital conjunctival cyst after a penetrating orbital injury: a case
      report].
AB  - We report a case of intraorbital conjunctival cyst following a penetrating
      orbitocranial injury. The patient was a 28-year-old male who was hospitalized
      with exophthalmos, retrobulbar pain and upper gaze disturbance of his left eye.
      When he was 4 years old, a thin iron rod had penetrated intracranially through
      the inner angle of his left orbit. He was hospitalized and treated conservatively
      for about two weeks. The left eye ball was intact and visual acuity was normal,
      although bloody fluid had continuously flowed out from the left inner angle of
      the conjunctival wound for a few days. He had been febrile to 39 degrees C and
      complained of headache for one week. Subsequentry, the symptoms gradually
      improved through conservative therapy. When he was a junior high school student,
      he noticed exophthalmos of his left eye. However, he had never been examined
      closely, until he was 28 years old. We suspect that he had suffered from
      meningitis caused by the penetrating orbitocranial injury, and had fortunately
      improved under the conservative therapy. On admission to our hospital, a
      craniogram showed fracture of the left orbital roof, and coronal and three
      dimensional computed tomography (CT) scans clearly demonstrated the orbital
      fracture. CT revealed a cystic mass in the retrobulbar space, and a porencephalic
      cyst in the medial basal frontal lobe. On magnetic resonance imaging (MRI) scans,
      both cysts were of low intensity on T1-weighted imaging, and of high intensity on
      T2-weighted images. Coronal and sagittal MRI scans showed that the two cysts were
      connected with each other through the fracture in the orbital roof. We diagnosed
      therefore that the orbital cyst was a herniated porencephalic cyst of the frontal
      lobe. Surgery was performed by a transcranial approach. The porencephalic cyst
      adhered to the fractured lesion of the frontal base but did not extend into the
      orbita. The intraorbital cyst was totally removed by opening the orbital roof
      including the fractured lesion. The cyst contained milky fluid. Postoperatively,
      the exophthalmos, retrobulbar pain and upper gaze disturbance showed gradual
      improvement. On histological examination, the cyst was found to be lined by non
      keratinized stratified squamous epithelium and was diagnosed as a conjunctival
      cyst. This case was considered to be one of traumatic conjunctival cysts caused
      by a penetrating orbitocranial injury. Orbital conjunctival cysts have been
      reported to comprise about 10% of orbital epidermoid and dermoid cysts. Of these
      cysts, traumatic conjunctival cysts are rare, and only a few cases have been
      described. The etiology and therapy of orbital conjunctival cysts are discussed.

PMID- 8752878
TI  - [A case of middle cranial fossa meningioma extending into the infratemporal
      fossa: an approach to the pterygoid extension of the sphenoid sinus via the
      infratemporal fossa].
AB  - A case of middle cranial fossa meningioma extending into infratemporal fossa and
      the pterygoid process is presented. The patient had a sphenoid sinus extending
      inferolaterally into the pterygoid process, which is known as pterygoid extension
      of the sphenoid sinus. This type of variation of the sphenoid sinus allowed a
      safe and well-oriented approach to the pterygoid process via the infratemporal
      fossa. The tumor extending into the pterygoid process was removed successfully
      without damaging any surrounding structures, e.g. maxillary nerve or Vidian
      nerve. However, pterygoid extension of the sinus is seen in only 40% of cases.
      Therefore, close preoperative examination with bone window CT scan is mandatory
      before employing this approach.

PMID- 8752880
TI  - [Myelopathy caused by hypertrophy of the posterior longitudinal ligament of the
      cervical spine in a patient with long-term hemodialysis].
AB  - A 48-year-old female was admitted to our hospital because of progressive gait
      deterioration over a period of 4 months. She had been treated by hemodialysis for
      14 years after bilateral nephrectomy. She originally suffered achondroplasia.
      Otherwise she was a healthy woman. Neurological examination showed weakness and
      hypesthesia below C5, accelerated deep tendon reflexes and inability in walking.
      T1 weighted magnetic resonance imaging revealed severe cord compression from C4
      to C6 due to an epidural isointensity mass located in the ventral surface of the
      dura. This mass was enhanced by a contrast medium. Anterior decompression
      followed by an autogenous vertebral bone graft at C4/5 and C5/6 was performed.
      The posterior longitudinal ligament was remarkably thickened resulting in severe
      cord compression. Histologically this thick ligament contained amyloid deposition
      both in the superficial and deep layers. Ossification was not noticed in the
      ligament. Diagnosis of hypertrophy of the posterior longitudinal ligament (HPLL)
      was made. HPLL is known to be frequently associated with herniated intervertebral
      discs or segmental ossification of the posterior longitudinal ligament (OPLL).
      Myelopathy in this patient with long-term hemodialysis was aggravated by HPLL
      without ossification due to imbalance of systemic metabolism such as amyloidosis.
      The authors report a unique case of HPLL caused by amyloidosis as one of the
      complications of chronic hemodialysis with special emphasis on its
      pathophysiology and management.

PMID- 8752881
TI  - [Acoustic neurinoma located exclusively in cerebellopontine angle cistern
      ("cisternal" acoustic neurinoma): a case report].
AB  - This is a case report of acoustic neurinoma which was located exclusively in the
      cerebellopontine angle (CPA) cistern and which did not extend into the internal
      auditory meatus ("cisternal" acoustic neurinoma). The 43-year-old female patient
      had signs of the left trigeminal nerve impairment including left face neuralgia.
      However, she did not have any neurootological symptom. No abnormal bony changes
      in the internal auditory meatus (IAM) were found by high-resolution bone-window
      CT. MRI showed a left CPA tumor of 25mm not extending into the IAM. The tumor was
      totally removed by the lateral suboccipital approach. It originated from the
      vestibular nerve medial to the porus acusticus and was located exclusively in the
      CPA cistern. No tumor extension into the IAM was confirmed. The cochlear nerve
      was involved in the tumor capsule and could not be preserved. The pathological
      diagnosis was that it was a neurilemmoma. Early diagnosis of "cisternal" acoustic
      neurinoma is difficult because it does not show neurootological symptoms in the
      early stage. The lateral suboccipital approach is appropriate for the removal of
      a "cisternal" acoustic neurinoma. However, in spite of the good preoperative
      hearing, the preservation of hearing is difficult because of the large tumor
      size.

PMID- 8752882
TI  - [The cases of acute spontaneous subdural hematoma].
AB  - In this paper, 10 cases of acute spontaneous subdural hematoma (ASSDH) among 149
      cases of all acute subdural hematoma (ASDH) were reported with a review of 36
      cases in the literature. The age of the patients with ASSDH ranged from 48 to 90
      years (mean age of 71.9 years), and the average age of ASDH patients was 52.4
      years. The male to female ratio of ASSDH and ASDH was 3:7 and 5:2, respectively.
      ASSDH patients were older than ASDH patients, and ASSDH patient tended to be
      female. Four cases of ASSDH patients had the past history of dementia. The
      outcome of 5 cases of ASSDH with general complications was fatal. During
      operation in all cases except one, spurting arterial rupture from a branch of the
      cortical artery adjacent to the Sylvian fissure was observed. It was presumed in
      the literature that the mechanism of the arterial rupture is gliding movement of
      the brain, tearing an arterial twig with dural attachment, or the existence of
      the junction of an arterial twig as an anatomically weak point. Hypertension,
      alcoholism, dementia, past history of subdural hematoma or subarachnoid
      hemorrhage may be important influencing factors in this mechanism.

PMID- 8752883
TI  - [A case of atlanto-axial rotatory fixation associated with Jefferson's fracture].
AB  - The authors present a case of atlanto-axial rotatory fixation associated with
      Jefferson's fracture. A 52-year-old man was admitted to our hospital complaining
      of severe neck pain and torticollis after a traffic accident. Cervical x-ray
      films showed fracture of the atlas. CT scans demonstrated traumatic subarachnoid
      hemorrhage and atlanto-axial rotatory fixation. The patient was managed with
      skull traction and reposition was achieved. Although he was maintained in a halo
      device for 4 months, rotary fixation recurred. He underwent posterior fusion
      between the atlas and axis. We review the literature and discuss the diagnostic
      problems and methods of treatment for atlanto-axial rotatory fixation.

PMID- 8752884
TI  - [Surgical approach for cervical dumbbell type neurinoma: posterior approach by
      partial hemilaminectomy with preservation of a facet joint].
AB  - We report on a case harboring a cervical dumbbell type neurinoma. The tumor was
      completely removed by a modified posterior approach, consisting of partial
      hemilaminectomies of C2 and C3 with preservation of the facet joint. The
      operative field under microscope was limited by the preserved facet joint of
      C2/3. However, sufficient bulk reduction of the epidural and paravertebral mass
      enabled us to obtain a good operative field. The paravertebral mass, which
      extended anteriorly to just beside the posterior aspect of the carotid sheath,
      was removed through the lateral space. The operative field was easily widened
      beside the right facet joint of C2/3 with partial removal of the posterior part
      of the transverse process of C2 and C3. The transit portion of the tumor to the
      normal nerve fiber was also identified through this space. The intracanalicular
      mass was removed by the partial hemilaminectomies of C2 and C3 without
      compressing the dural sac. Following sufficient reduction of the bulk, the right
      vertebral artery was identified at the anteromedial margin of the enlarged
      intervertebral foramen. Finally the intradural part of the tumor was removed
      through this space. Our modified posterior approach is a less invasive method to
      the bony elements of the cervical vertebrae and may minimize the incidence of
      postoperative instability and angular deformity. This approach also eliminates
      the necessity of long postoperative immobilization using a rigid cervicothoracic
      brace.

PMID- 8752885
TI  - [Structure of cytochrome c oxidase from Paracoccus denitrificans at 2.8A
      resolution].

PMID- 8752886
TI  - [Structures of metal centers of bovine heart cytochrome c oxidase].

PMID- 8752887
TI  - [Virus-induced apoptosis as a host defence mechanism].

PMID- 8752888
TI  - [Reaction mechanism of HIV-1 integrase].

PMID- 8752889
TI  - [In vitro studies of chromatin structure and transcriptional regulation].

PMID- 8752890
TI  - [Inactivation of X-chromosome and Xist gene].

PMID- 8752891
TI  - [Modified cyclodextrins as molecule-recognition sensors].

PMID- 8752892
TI  - [Transposon tagging using transgenic plants].

PMID- 8752893
TI  - Sophisticated strategies for information encounter in the lymph node: the
      reticular network as a conduit of soluble information and a highway for cell
      traffic.
AB  - The lymph node is the crossroad in which soluble signals and cells carried by
      lymph meet lymphocytes emigrating from blood. Efficient interactions among these
      elements depend on the reticular network, which comprises reticular fibers,
      related extracellular matrix components, and associated fibroblastic reticular
      cells. This network provides a three-dimensional scaffold for attachment of APCs
      and pathways for the migration of T cells to these APCs. In addition, the network
      constitutes a miniature conduit system for bulk flow delivery of soluble
      molecules to distinct sites in the paracortex, particularly the high endothelial
      venule. The delivered mediators, such as chemokines, regulate the phenotype of
      the high endothelial venule, the recruitment of lymphocytes, and the behavior of
      the recruited lymphocytes. Thus, the reticular network is a multifunctional
      infrastructure that facilitates encounters of cells with other cells and factors
      necessary for effective and efficient immune surveillance.

PMID- 8752894
TI  - Defective Rho GTPase regulation by IL-1 beta-converting enzyme-mediated cleavage
      of D4 GDP dissociation inhibitor.
AB  - GTPases of the Rho family regulate many aspects of inflammatory cell activity,
      including motility, formation of toxic oxygen metabolites, and generation of
      proinflammatory cytokines. Defective regulation of such signaling pathways leads
      to a variety of acute and chronic inflammatory disorders, although the mechanisms
      by which this occurs have not been well defined. We describe in this work
      specific proteolytic cleavage of D4 GDI, a critical regulator of Rho GTPase
      activity in inflammatory leukocytes, by IL-1 beta-converting enzyme (ICE).
      Cleavage of D4 GDI by ICE occurs at Asp55, leading to the formation of the
      truncated D4 that is unable to effectively bind and regulate GTPases of the Rho
      family. Our data suggest that activation of ICE protease(s) at inflammatory sites
      leads to defective Rho GTPase regulation. Release of these critical regulatory
      proteins may contribute substantially to the inflammatory response at these
      sites, exacerbating and perpetuating the resulting tissue damage.

PMID- 8752895
TI  - The weak CD8+ CTL response to an influenza hemagglutinin epitope reflects limited
      T cell availability.
AB  - One of the two class I MHC (H-2Kd)-restricted immunogenic regions identified on
      the influenza virus strain A/Japan/57 (H2N2) hemagglutinin (HA) encompasses two
      distinct, partially overlapping epitopes. These epitopes map to residues 204 to
      212 (JHA 204-212) and 210 to 219 (JHA 210-219), respectively. When we
      investigated the magnitude of the CTL responses of H-2d BALB/c mice to these two
      epitopes, we found that the JHA 204-212 nonamer epitope is immunodominant,
      eliciting vigorous CTL responses in BALB/c mice immunized with A/Japan/57 virus.
      In contrast, the CTL response to the JHA 210-219 decamer epitope was weak and
      variable. The subdominance of the JHA 210-219 was not due to low affinity binding
      of JHA 210-219 to H-2Kd or to inefficient processing of this epitope in vivo.
      Rather, an analysis of CTL precursor (pCTL) frequency by limiting dilution showed
      that the frequency of pCTL to the JHA 210-219 epitope was at least 10-fold lower
      than the frequency of pCTL to the JHA 204-212 epitope, implying that the low and
      variable response to the JHA 210-219 epitope was due to a limited number of CD8+
      T cell precursors directed to JHA 210-219. This hypothesis was further supported
      by the finding of limited heterogeneity in reactivity pattern displayed by short
      term bulk cultures of the JHA 210-219-specific CTLs for cross-reactive epitopes.
      Implications of these findings for vaccine design and for T lymphocyte function
      and repertoire development are discussed.

PMID- 8752896
TI  - Sequential acquisition of mitochondrial and plasma membrane alterations during
      early lymphocyte apoptosis.
AB  - When cells undergo nuclear apoptosis (chromatin condensation, DNA fragmentation),
      they already manifest at least three alterations that can be quantified
      cytofluorometrically at the single-cell level: 1) a loss of mitochondrial
      transmembrane potential (delta psi m), 2) an increased production of superoxide
      anions, and 3) the aberrant exposure of phosphatidylserine (PS) residues on the
      outer plasma membrane leaflet. This latter alteration allows for the phagocytic
      recognition/elimination of apoptotic cells. In this work, we show that cells
      first undergo the delta psi m disruption and that PS exposure only affects cells
      that already have a low delta psi m. Pharmacologic modulation of apoptosis with
      inhibitors of macromolecule synthesis or proteases, as well as with drugs
      stabilizing the delta psi m, indicates that delta psi m disruption and PS
      exposure are coregulated. Interventions on apoptosis-regulatory genes (p53, bcl
      2) confirm the coregulation of delta-psi-m disruption, PS exposure, and nuclear
      signs of apoptosis. In all conditions in which apoptosis is prevented, the delta
      psi m remains stable and PS cannot be detected on the cell surface. Reactive
      oxygen species do not contribute to PS exposure, based on two lines of evidence.
      First, among thymocytes undergoing apoptosis in response to dexamethasone, delta
      psi mlow cells first expose PS and then hyperproduce superoxide anion. Second,
      exogenous sources of reactive oxygen species or the superoxide anion-generating
      drug menadione fail to cause rapid PS exposure. Instead, direct interventions on
      mitochondria using inhibitors of the respiratory chain or the F1 ATP synthase
      cause PS exposure in cells subsequent to delta psi m disruption. This effect is
      also obtained in anucleate cells, indicating that the nucleus does not intervene
      in the sequence of events coupling mitochondrial dysfunction to PS exposure.
      Altogether, these data underline the functional impact of mitochondrial
      alterations on the apoptotic process.

PMID- 8752897
TI  - IFN-alpha induces autoimmune T cells through the induction of intracellular
      adhesion molecule-1 and B7.2.
AB  - Insulin-dependent diabetes is an autoimmune disease characterized by the loss of
      the insulin-producing beta cells and the appearance of autoreactive (anti-islet)
      T cells. The mechanism by which these autoimmune T cells become activated has not
      been resolved. We demonstrate that the expression of IFN-alpha by the pancreatic
      beta cells leads to the development of CD4+ T cells that proliferate in the
      presence of islet Ags. These autoreactive T cells have a Th1 phenotype and are
      able to lyse islet cells, possibly through an indirect, cytokine-mediated
      mechanism. We also demonstrate that the pancreatic infiltrating leukocytes in the
      transgenic mice express increased levels of 87.2 and ICAM-1 and that IFN-alpha
      can directly induce these two costimulatory molecules on nontransgenic splenic
      APCs. Treatment of the transgenic mice with Abs against these costimulatory
      molecules demonstrated that B7.2 is essential for the induction of autoreactive T
      cells, whereas ICAM-1 contributes to but is not essential for the formation of
      these autoreactive cells. As B7.2 and ICAM-1 are able to synergize to provide
      costimulatory signals to naive T cells under conditions of limiting Ag, we
      propose that IFN-alpha expression normally contributes to the development of an
      anti-viral cellular immune response, but that uncontrolled expression of this
      cytokine will induce autoimmunity.

PMID- 8752898
TI  - T cell regulation in adult transplantation tolerance.
AB  - An encounter of the mature immune system with Ag usually leads to an immune
      response. If Ag is administered with CD4- and CD8-specific mAbs, the outcome of
      the response can be tolerance. This form of tolerance is peripheral, Ag specific,
      and maintained lifelong, and is associated with the suppression of nontolerant
      cells by CD4 cells of the tolerant host. Here we demonstrate that the degree of
      suppression is dependent on the number of suppressor cells. A neutralizing anti
      IL-4 Ab was partially able to inhibit suppression, indicating a role for IL-4 in
      the regulation of Th1 rejection responses.

PMID- 8752899
TI  - Tyrosine phosphorylation of Shc is not required for proliferation or viability
      signaling by granulocyte-macrophage colony-stimulating factor in hematopoietic
      cell lines.
AB  - The receptor for human granulocyte-macrophage (GM)-CSF (GMR) is a heterodimer,
      consisting of an alpha-chain (GMR alpha) and a beta-chain (GMR beta). While GMR
      alpha is capable of binding GM-CSF, GMR beta is necessary for signal
      transduction. Phosphorylation of one or more tyrosine residues in GMR beta is an
      early event in signaling. We have recently demonstrated that tyrosine 750 (Y750)
      in GMR beta is a site of GM-CSF-induced phosphorylation and this site may
      contribute to the maintenance of cellular viability in response to GM-CSF. To
      investigate possible contributions made by additional GMR beta cytoplasmic
      tyrosine residues to receptor function, we mutated other selected tyrosine
      residues to phenylalanine and tested for any defects in signaling. in the present
      study, we show that Y577 is required for phosphorylation of Shc and an Shc
      associated p140 in response to GM-CSF. Y577 is also required for association of
      Shc with GRB2. Y577 does not appear to be necessary for GM-CSF-induced
      proliferation and survival. GMR beta with a mutated Y577 is able to transduce
      signals leading to the activation of the Raf-1 pathway and the Jak-Stat pathway.
      Interestingly, mutation of Y750 reduced detectable GM-CSF-induced tyrosine
      phosphorylation of GMR beta, suggesting that the reduction of Shc phosphorylation
      associated with that mutant might be actually due to a failure to phosphorylate
      Y577. These data indicate that the phosphorylation of Shc in response to GM-CSF
      is not required for proliferation or viability signaling in these cells.

PMID- 8752900
TI  - Type I (CD64) and type II (CD32) Fc gamma receptor-mediated phagocytosis by human
      blood dendritic cells.
AB  - Three classes of Fc receptors for IgG, Fc gamma RI (CD64), Fc gamma RII (CD32),
      and Fc gamma RIII (CD16), are expressed on blood leukocytes. Although Fc gamma R
      are important phagocytic receptors on phagocytes, most reports suggest that
      dendritic cells lack Fc gamma R-mediated phagocytosis and express significant
      levels of only CD32. We now report that phagocytically active forms of both CD64
      and CD32 are expressed significantly on at least one subset of human blood
      dendritic cells. Countercurrent elutriation and magnetic bead selection were used
      to rapidly enrich subsets of blood dendritic cells (CD33brightCD14-HLA
      DRbrightCD83-) and monocytes (CD33brightCD14brightHLA-DRdimCD83-). Upon culture
      for 2 days, dendritic cells became CD83-positive and markedly increased HLA-DR
      expression, whereas monocytes did not express CD83 and exhibited reduced levels
      of HLA-DR. Constitutive CD64 expression was identified on this circulating
      dendritic cell population, but at a lower level than on monocytes. CD64
      expression by dendritic cells and monocytes did not decrease during 2 days in
      culture, and was up-regulated on both cell types following incubation with IFN
      gamma. Freshly isolated blood dendritic cells performed CD64- and CD32-mediated
      phagocytosis, although at a lower level than monocytes. Dendritic cells generated
      by culture of adherent mononuclear cells in granulocyte-macrophage CSF and IL-4
      also up-regulated CD64 following IFN-gamma stimulation, and mediated CD64
      dependent phagocytosis. These results indicate that both CD64 and CD32 expressed
      on blood dendritic cells may play a role in uptake of foreign particles and
      macromolecules through a phagocytic mechanism before trafficking to T cell
      reactive areas.

PMID- 8752901
TI  - Regulation of the B cell response to T-dependent antigens by classical pathway
      complement.
AB  - Mice deficient in complement components C3 (C3 -/-) and C4 (C4 -/-) were found to
      have a profound defect in their Ab response to a T-dependent Ag (bacteriophage
      (phi X174). Characterization of the deficient mice demonstrated a diminished
      level of peanut agglutinin+ germinal centers and a failure in isotype switching
      despite normal B cell signaling in vitro. The nature of the defect was found to
      lie at the B cell level, as the T cells were primed in C3- and C4-deficient mice
      as well as those in wild-type mice. These results, and the finding that the
      defect could be partly reversed by a 10-fold increase in Ag dose, support the
      hypothesis that covalent attachment of complement ligands, i.e., C3b and C3d to
      the Ag-Ab complex, increases its immunogenicity.

PMID- 8752902
TI  - Delayed-type hypersensitivity in mast cell-deficient mice: dependence on
      platelets for expression of contact sensitivity.
AB  - Previous studies of cutaneous T cell-mediated responses in mice have obtained
      pharmacologic, morphologic, and immunologic evidence pointing to a critical role
      for local mast cells in release of the vasoactive amine serotonin (5-HT) to
      mediate early, initiating events that are required for elicitation of these
      responses. However, the role of mast cells in initiating these T cell-mediated
      cutaneous responses has been questioned due to the presence of relatively intact
      delayed-type hypersensitivity responses, such as contact sensitivity (CS), in
      mast cell-deficient mice whose skin contains only 1 % normal mast cell numbers.
      The contribution of other potential local sources of 5-HT, such as circulating
      platelets, at the site of a delayed-type hypersensitivity or CS response in these
      mast cell-deficient strains, has not been investigated. Therefore, we studied the
      effect of systemic platelet depletion, produced with an anti-platelet Ab, on
      blood and tissue levels of 5-HT, and on in vivo T cell-mediated cutaneous
      sensitivity responses, in W/Wv and Sl/Sld mast cell-deficient mice. The results
      showed that: 1) platelet depletion severely reduced whole blood 5-HT; 2) tissue
      levels of 5-HT, in mast cell-deficient mice, depended in large part on the
      presence of circulating platelets, and 3) specific depletion of platelets
      markedly suppressed CS responses in both W/Wv and Sl/Sld mast cell-deficient
      mice, and only moderately reduced CS in normal +/+ congenic mast cell-sufficient
      controls, but did not decrease CS in beige mice, with platelet granules that are
      defective in storage of 5-HT. We concluded that platelets may provide 5-HT
      crucial for the initiation of cutaneous T cell-mediated immune responses, such as
      CS.

PMID- 8752903
TI  - Th1 development of naive CD4+ T cells is inhibited by co-activation with anti-CD4
      monoclonal antibodies.
AB  - Co-activation of CD4+ T cells by anti-CD4 mAb strongly enhances the proliferation
      of these T cells. We have analyzed the influence of CD4-mediated co-activation on
      Th cell differentiation. Our data demonstrate that activation of high density
      (HD)-CD4+ T cells by immobilized anti-CD3 mAb in combination with immobilized
      anti-CD4 mAb led to a strong inhibition of Th1 differentiation and to a variable
      but significant induction of Th2 development. Priming of highly enriched Mel
      14highCD4+ T cells in the presence of anti-CD4 mAb also resulted in a pronounced
      suppression of secondary IFN-gamma production, indicating that the Th1
      development of naive CD4+ T cells is inhibited by co-activation via CD4. In
      contrast to HD-CD4+ T cells, CD4-induced costimulation of MEL-14highCD4+ T cells
      did not result in a primary and secondary IL-4 production. Hence, these results
      suggest that a MEL-14low population within the HD-CD4+ T cell fraction was the
      source of the endogenous IL-4 and imply, in addition, that co-activation via CD4
      inhibits the development of Th1 cells from naive CD4+ T cells independently from
      endogenous IL-4. This assumption is further corroborated by the fact that neither
      the application of neutralizing anti-IL-4 mAb nor the use of T cells from IL-4
      knockout mice could prevent CD4-mediated inhibition of Th1 development. The Th1
      inhibiting effect of anti-CD4 mAb could not be reversed by the application of the
      Th1 inducer IL-12. On the contrary, the secondary IL-4 production of HD-CD4+ T
      cells as an indicator of Th2 differentiation, which was promoted by anti-CD4 mAb,
      was enhanced even in the presence of IL-12. Therefore, our results suggest that
      co-activation of naive CD4+ T cells by anti-CD4 mAb directly and selectively
      inhibits Th1 differentiation of naive dense CD4+ T cells.

PMID- 8752904
TI  - Gamma delta TCR+ hybridomas derived from mice preimmunized via the portal vein
      adoptively transfer increased skin allograft survival in vivo.
AB  - C57BL/6 mice receiving pretransplant immunization with C3H.SW spleen cells via
      the portal vein, but not the vena cava, show Ag-specific delayed rejection of
      allogeneic C3H.SW skin grafts. This delayed rejection is not seen if
      preimmunization is performed in gamma delta TCR knockout (C57BL/6-Tcrdtm1Mom)
      mice. gamma delta TCR+ and alpha beta TCR+ hybridoma cells were prepared from
      Peyer's patch cells harvested from C57BL/6 mice 4 days following portal venous
      immunization with 100 x 10(6) irradiated C3H.SW spleen cells and skin grafting
      with C3H.SW tail skin. After recloning, these hybridoma cells were tested for
      cytokine production in vitro following restimulation with irradiated C3H.SW
      spleen cells and for their ability to delay rejection of C3H.SW skin grafts after
      adoptive transfer to C57BL/6 mice. Delayed graft rejection was a function of
      cells that showed preferential production of IL-10, not IFN-gamma, in vitro,
      independent of the source (vena cava or portal vein immunized mice) or the TCR
      phenotype of the hybridoma. Simultaneous infusion of anti-IL-10 mAb abolished
      this graft prolongation effect of transferred gamma delta TCR+ hybridomas.
      Hybridoma cells producing IL-10 on restimulation could polarize cytokine
      production from freshly stimulated mesenteric lymph node away from production of
      IL-2 and IFN-gamma, and toward IL-4, IL-10, and TGF-beta production. This
      immunoregulation by hybridoma cells in vivo and in vitro was observed even for
      third party Ag-stimulated mice/cells as long as the hybridoma cells themselves
      received stimulation with their specific Ag.

PMID- 8752905
TI  - The role of the B7-1a molecule, an alternatively spliced form of murine B7-1
      (CD80), on T cell activation.
AB  - B7 molecules (CD80 (B7-1) and CD86 (B7-2/B70)) on APCs provide costimulatory
      signals for T cell proliferation. We previously described the presence of an
      alternatively spliced form of murine CD80 (previously termed MB7-2 and renamed as
      B7-1a) that completely lacks the second Ig-like domain coded by exon 3 in
      activated murine B cells. in this study, we first examined whether B7-1a mRNA can
      be detected in vivo by RNase protection assay. The expression of B7-1a mRNA was
      only detected in lymphoid organs although the level of expression was lesser than
      that of CD80 mRNA. However, we demonstrated that the expression of B7-1a mRNA
      like CD80 mRNA was considerably augmented in spleen cells treated with either LPS
      in vitro or OVA/CFA conjugate in vivo. We next determined the functional activity
      of B7-1a using Chinese hamster ovary (CHO) cells transfected by B7 genes. When
      resting T cells were cocultured with CHO cells expressing B7-1a molecules in the
      presence of PMA/ionomycin, T cell proliferation was not detected, while CHO cells
      either expressing CD80 or CD86 could promote the proliferation of resting T
      cells. in contrast to resting T cells, CHO cells expressing B7-1a could support
      the proliferation of activated T cells. Thus, costimulatory activity of B7-1a
      molecules was dependent upon the activation stage of T cells. Therefore the IgV
      like region of CD80 contains a critical region for functional interaction with
      its ligands and can transduce a costimulatory signal for T cell proliferation.

PMID- 8752906
TI  - Differential effect of the immunomodulator AS101 on B7-1 and B7-2 costimulatory
      molecules: role in the antitumoral effects of AS101.
AB  - The CD28 receptor on T cells with its ligand B7, representing the best
      characterized example of costimulation, has recently been demonstrated to
      interact with two different ligands: B7-1 and B7-2. AS101 (ammonium
      trichloro[dioxoethylene-O,O']tellurate), a synthetic immunomodulator with minimal
      toxicity, was previously shown to stimulate both mouse and human cells to
      proliferate and secrete a variety of cytokines. We recently found that treatment
      of advanced cancer patients or tumor-bearing mice with AS101 results in a clear
      predominance of Th1 responses with a concomitant decrease in Th2 response. Our
      present study demonstrates that AS101 differentially affects B7-1 and B7-2
      molecule expression on mouse macrophages: it up-regulates B7-1 expression in a
      dose-dependent manner without affecting B7-2 expression, which leads to a
      profound macrophage costimulatory activity of purified T cells with soluble anti
      CD3. Our results also demonstrate the differential inhibitory effect of IL-10 on
      T cell activation in the presence of AS101-stimulated accessory cells (AC). We
      show that when stimulated with AS101, AC-dependent T cell activation was more
      resistant to inhibition by IL-10 compared with AC stimulated by LPS. This was due
      to the partial resistance of AS101-stimulated macrophages to the down-regulation
      of B7-1 expression by IL-10. In vivo studies with AS101-treated tumor-bearing
      mice revealed that the predominance in Thl responses--marked by an increase in
      IFN-gamma and a decrease in IL-4--may be associated in part with the ability of
      AS101 to up-regulate B7-1 expression, which is also related to its antitumoral
      effects. These results suggest that AS101 may be clinically effective in
      conditions involving dysfunctional cytokine production.

PMID- 8752907
TI  - Bcmd governs recruitment of new B cells into the stable peripheral B cell pool in
      the A/WySnJ mouse.
AB  - The A/WySnJ mouse provides a genetic model for studying new B cell selection into
      the stable peripheral B cell pool. Unlike the related A/J strain, the A/WySnJ has
      a single, autosomal codominant gene defect, Bcmd, resulting in a profound
      peripheral B cell deficiency. Here, continuous in vivo bromodeoxyuridine labeling
      and immunofluorescence analysis showed normal bone marrow B cell genesis but
      excessive B cell loss from the marrow and each peripheral pool in A/WySnJ. The
      A/WySnJ immature B220low/HSAhigh splenic B cell pool was 79% smaller, had a 69%
      slower renewal rate, and its cells had a 29% shorter average half-life than A/J.
      The A/WySnJ mature B220high/HSAlow splenic B cell pool was 92% smaller, had an
      83% slower renewal rate, and its cells had a 56% shorter average half-life. In
      reciprocal chimeras, the A/WySnJ marrow failed to repopulate the peripheral B
      cell pool in A/J mice, whereas the A/J marrow fully reconstituted the A/WySnJ
      mice. Histochemistry revealed disordered splenic architecture in A/WySnJ, with
      few primary lymphoid follicles and a second abnormal phenotype, mastocytosis.
      There was no common genetic basis for B cell deficiency and mastocytosis in the
      F2 progeny of an (A/WySnJ x CAST/Ei)F1 intercross. We conclude that Bcmd is
      expressed in bone marrow cells, most likely B cells, where it hinders short-lived
      B cell maturation to a long-lived phenotype with the potential to form memory B
      cells.

PMID- 8752908
TI  - Peripheral blood dendritic cells express Fc epsilon RI as a complex composed of
      Fc epsilon RI alpha- and Fc epsilon RI gamma-chains and can use this receptor for
      IgE-mediated allergen presentation.
AB  - Originally limited to basophils and mast cells, the spectrum of high affinity IgE
      receptor (Fc epsilon RI-bearing cells has expanded recently to include Langerhans
      cells, dermal dendritic cells (DC), monocytes, and eosinophils. As a result of
      studies on the distribution, structure, and function of Fc epsilon RI on APCs, we
      discovered a minor nonbasophil, nonmonocyte PBMC population that can bind IgE via
      Fc epsilon RI. This receptor occurs on the surface of these cells as a multimeric
      structure containing Fc epsilon RI alpha- and Fc epsilon RI gamma-chains but,
      unlike its counterpart on basophils, lacking Fc epsilon RI beta. Further
      experiments revealed that these Fc epsilon RI alpha gamma-expressing cells
      closely resemble peripheral blood DC by immunophenotype (HLA-DRhigh, HLA-DQhhigh;
      CD4+, CD11a+, CD32+, CD33+, B7/2 (CD86)+; CD11blow, CD14low, CD40low, CD54low,
      CD64low) and cell morphology. These features allowed us to isolate Fc epsilon RI
      expressing DC from the peripheral blood and to investigate their
      immunostimulatory properties. We found Fc epsilon RI-positive DC to be efficient
      stimulators of both primary (allogeneic MLR) and Fc epsilon RI/IgE-dependent,
      secondary T cell responses at low cell numbers. Thus, Fc epsilon RI-expressing DC
      may not only amplify established type I allergic immune reactions but, unlike Fc
      epsilon RI-positive semiprofessional APCs, may be able to prime naive T cells to
      common and/or cryptic epitopes of IgE-reactive Ags.

PMID- 8752909
TI  - Chemical denaturation and modification of ovalbumin alters its dependence on
      ubiquitin conjugation for class I antigen presentation.
AB  - Class I presentation of microinjected native OVA by a temperature-sensitive
      ubiquitin conjugation mutant, ts85, but not wild-type murine cells, was markedly
      inhibited following incubation at a nonpermissive temperature. In contrast, the
      nonpermissive temperature did not affect class I presentation of a minimal OVA
      peptide expressed in the cytosol. Therefore, these results provide a second
      example in which a temperature sensitive mutation in the ubiquitin conjugation
      pathway inhibits MHC class I presentation of native OVA. Surprisingly, incubation
      at the nonpermissive temperature did not inhibit class I presentation of
      chemically denatured and alkylated OVA microinjected into the cytosol of mutant
      cells. Similarly, the presentation of endogenously synthesized OVA (which is
      expressed from a recombinant vaccinia virus and, presumably, is misfolded in the
      cytosol) was also not inhibited in both mutant cell lines. Methylation of the
      lysine groups in denatured OVA, which blocks ubiquitin conjugation, reduced but
      did not eliminate the presentation of denatured OVA, providing evidence for both
      ubiquitin-dependent and ubiquitin-independent pathways for class I presentation.
      In contrast, a proteasome inhibitor blocked class I presentation of all forms of
      OVA, while a control peptide aldehyde was not inhibitory. These results indicate
      that modification of the structure of a protein can influence its requirements
      for ubiquitin conjugation for efficient class I presentation, with the key
      alteration possibly being the loss of proper conformation. However, regardless of
      the form of the Ag, the proteasome appears to be required for generating peptides
      from both endogenously synthesized and microinjected OVA for class I
      presentation.

PMID- 8752910
TI  - TCR triggering of anergic CD4 T cells in murine AIDS induces apoptosis rather
      than cytokine synthesis and proliferation.
AB  - Murine AIDS (MAIDS) induced by infection of C57BL/6 mice with a mixture of
      retroviruses known as LP-BM5 is characterized by lymphadenopathy, splenomegaly,
      and T and B cell dysfunction. By labeling with bromodeoxyuridine in vivo, we
      found vigorous CD4 T cell proliferation during the initial stages of infection,
      yet a loss in their ability to function both in vivo and in vitro. In addition, a
      significant fraction of the CD4 T cell population in infected mice undergoes
      spontaneous apoptosis in vivo. Upon in vitro stimulation with anti-CD3 plus PMA,
      anergic CD4 T cells from mice with MAIDS fail to progress through the cell cycle
      (G0/G1 arrest), and a fraction of the cells undergoes apoptosis. The addition of
      IL-2 along with TCR-mediated stimulation not only fails to rescue CD4 T cells
      from apoptosis, but enhances activation-induced cell death. To further understand
      the regulation of the suicide pathway(s) of anergic CD4 T cells vs the cytokine
      synthesis pathway(s) of normal CD4 T cells, we evaluated their expression of Bcl
      2 protein. As infection progresses, the expression of Bcl-2 among CD4 T cells
      declines and drops further when CD4 T cells are restimulated through the TCR in
      vitro. These results suggest that this CD4 T cell immunodeficiency in MAIDS
      includes a TCR-induced program of activation-induced cell death and an uncoupling
      from cytokine synthesis pathways and proliferation of CD4 T cells. The decline in
      Bcl-2 expression may be in part responsible for this reprogramming.

PMID- 8752911
TI  - CD28 costimulation prevents cell death during primary T cell activation.
AB  - CD28 has been demonstrated to play an important role in augmenting T cell
      proliferation and effector function. Costimulation through CD28 has also been
      reported to enhance human T cell survival. in this report, we have further
      investigated the role of CD28 in regulating T cell survival by comparing the
      survival characteristics of T cells from wild-type and CD28-deficient mice. CD28
      costimulation of anti-CD3-activated cells augmented the viability of T cells from
      wild-type but not from CD28-deficient mice. CTLA4Ig treatment reduced wild-type T
      cell viability to a level comparable with CD28-deficient T cells. The ability of
      CD28 to enhance survival during T cell activation correlated positively with its
      ability to up-regulate the protein product of the cell survival gene bcl-xL. No
      differences in the expression of either Bcl-2 or Fas were observed between wild
      type and CD28-deficient T cells. The CD28-dependent enhancement of cell survival
      during in vitro activation was found to be independent of Fas expression, as CD28
      costimulation enhanced T cell survival to comparable levels in both wild-type and
      lpr animals. Cell death in CD28-deficient animals and in wild-type animals
      treated with CTLA4Ig displayed the morphologic characteristics of apoptosis.
      Additionally, inhibitors of ICE proteases could reverse cell death induced by TCR
      engagement in the absence of CD28 costimulation. Thus, CD28 costimulation not
      only enhances the proliferative expansion of cells activated through the TCR but
      also increases the likelihood that individual cells survive during T cell
      activation.

PMID- 8752912
TI  - The effect of IL-2 treatment on transcriptional attenuation in proto-oncogenes
      pim-1 and c-myb in human thymic blast cells.
AB  - IL-2 is the major mitogenic cytokine for mature human T cells. This growth factor
      has been shown previously to induce the expression of a number of genes,
      including structural proteins, proto-oncogenes, and metabolic enzymes. Multiple
      mechanisms, including increases in mRNA stability, protein synthesis, and new
      transcriptional initiation, have been studied to determine how IL-2 induces such
      a wide variety of genes. The following studies show that a release of
      transcriptional attenuation is important in IL-2-induced gene expression. A
      thymic blast cell system was developed and used to demonstrate that IL-2-deprived
      cells have a marked attenuation of transcription in the 3' ends of the pim-1 and
      c-myb genes. IL-2 stimulation removes this attenuation and leads to read-through
      transcription. This effect is gene-specific, as demonstrated by the fact that
      GAPDH is not attenuated in unstimulated cells. The IL-2-mediated relief of
      attenuation occurs within 1 h of IL-2 stimulation and is insensitive to the
      translation inhibitor cycloheximide, suggesting that new protein synthesis is not
      necessary. Further, the effect is insensitive to the immunosuppressant
      cyclosporin A, but is sensitive to rapamycin and the tyrosine kinase inhibitor
      genistein. These studies demonstrate that release of transcription attenuation is
      a mechanism used to induce gene expression in response to IL-2 treatment.

PMID- 8752913
TI  - Introduction of exogenous antigens into the MHC class I processing and
      presentation pathway by Drosophila antennapedia homeodomain primes cytotoxic T
      cells in vivo.
AB  - The homeodomain of the Antennapedia molecule (AntpHD) spontaneously crosses
      cellular membranes and can be used to deliver up to 50 additional amino acids to
      the cytoplasm. We exploited this approach to deliver antigenic peptides to the
      MHC class I processing and presentation pathway. AntpHD-based fusion peptides
      expressing the 170-179 HLA-Cw3 CTL epitope (pCw3) were produced in bacteria.
      Incubation of these fusion peptides with H-2d target cells resulted in efficient
      delivery to the cytosol as indicated by protease resistance and confocal
      microscopy. Moreover, this introduction of an exogenous Ag resulted in
      sensitization of the cell to lysis by a CTL clone specific for the 170-179 HLA
      Cw3-derived peptide. Sensitivity of the Ag processing to brefeldin A but not to
      chloroquine is consistent with the delivery of AntpHD fusion peptides to the
      conventional class I-associated processing pathway. Immunization of DBA/2 (H-2d)
      mice with AntpHD pCw3 fusion peptide in the presence of SDS primed H-2Kd
      restricted HLA-Cw3-specific CTL. Similar results were obtained with AntpHD fusion
      peptides expressing the 147-156 influenza nucleoprotein peptide. The strategy
      outlined in this paper provides a new approach for introducing molecules into the
      MHC class I Ag-presenting pathway. This approach has clear relevance to the
      design of synthetic peptide-based vaccines.

PMID- 8752914
TI  - p70 S6 kinase sensitivity to rapamycin is eliminated by amino acid substitution
      of Thr229.
AB  - Rapamycin, which forms a complex with FK506-binding protein and FK506-binding
      protein-rapamycin-associated protein, induces immunosuppression through an as yet
      undefined pathway. Our previous studies demonstrated that rapamycin inactivates
      p7Os6k, which results in the inhibition of translation of ribosomal proteins.
      Here, we analyzed the mechanism of inactivation of p70s6k by rapamycin using site
      directed mutagenesis of the phosphate acceptor site. We introduced a point
      mutation at Thr229 in the catalytic subdomain VIII of p7Os6k because Thr229 of
      p7Os6k corresponds to the phosphorylation site of mitogen-activated protein
      kinases by mitogen-activated protein kinase kinase and to the autophosphorylation
      site of protein kinase A whose phosphorylation is required for its full
      activation. Thr229 of rat p70s6k was substituted by either a neutral amino acid
      Ala (T229A) or by an acidic amino acid Glu (T229E). T229A-P70s6k, expressed in
      COS cells, migrated faster in SDS-polyacrylamide gels than wild-type p70s6k, and
      this mutation completely ablated the catalytic activity of the kinase. In
      contrast, T229E-p70s6k migrated more slowly in SDS-polyacrylamide gels, but
      demonstrated partial kinase activity (approximately 20% compared with the wild
      type). These data indicate that the negative charge at Thr229 which is normally
      achieved by phosphorylation of the residue, is important for the catalytic
      function of p70s6k. Further, the residual activity of T229E-p70s6k was not
      affected by rapamycin, implying that rapamycin-induced inactivation of p70s6k may
      be caused by dephosphorylation or impaired phosphorylation of Thr229.

PMID- 8752915
TI  - Characterization of a T cell line specific to an anti-Id antibody related to the
      carbohydrate antigen, sialyl SSEA-1, and the immundominant T cell antigenic site
      of the antibody.
AB  - The stage-specific embryonic Ag-1 (SSEA-1) is a carbohydrate Ag and regarded as
      an onco-developmental Ag. Sialyl SSEA-1 Ag, the sialylated form of SSEA-1, is
      frequently expressed in human cancer cells as well as in murine cancer cells. A
      mAb, FH-6, was shown to specifically recognize the Ag. We have generated five
      anti-Id Abs directed to the paratope-related idiotopes of the FH-6 Ab. One of
      these anti-Id Abs, Id-F2, increased the survival of host mice that were
      inoculated with Meth-A cells expressing the sialyl SSEA-1 Ag. To clarify the
      exact mechanism underlying the antitumor effect of the anti-Id Ab, we established
      a T cell line that recognized Id-F2 in association with MHC class II molecules.
      The T cell line was CD4+V beta 8+, and produced IL-2, exhibiting helper activity
      for B cells. The VH CDR2 region of the Id-F2 amino acid sequences turned out to
      be strongly immunogenic to T cells. When the immune complexes, consisting of the
      sialyl SSEA-1 Ag, FH-6, and Id-F2, were formed at the Meth-A cell-surface, the T
      cell line showed a strong proliferative response. The possible roles played by
      such T cell subsets in the anti-tumor effect are discussed.

PMID- 8752916
TI  - Self-MHC-restricted peptides recognized by an alloreactive T lymphocyte clone.
AB  - Alloreactive T lymphocytes are readily detected in unprimed animals although they
      have never encountered the alloantigen before. This well-established phenomenon
      is usually explained with the assumption that a self-MHC molecule complexed with
      a defined peptide resembles the allo-MHC molecule with another peptide and
      induces the corresponding T cell specificities. Here, for the first time and in
      support of this hypothesis, self-MHC-restricted peptides are described for a T
      cell clone that was induced with allo-MHC. The allo-MHC-specific CTL clone 2C was
      derived from a H-2b mouse and recognizes H-2Ld complexed with the naturally
      occurring endogenous peptide LSPFPFDL. H-2Kb was shown to be involved in positive
      selection of its TCR, and peptides associated with this MHC molecule are
      implicated in the process. To identify such peptides, positional scanning with
      random peptide libraries combined with an iterative approach was employed.
      Several active peptides were found and the most efficient, SIYRYYGL, was chosen
      for further studies. Recognition by 2C of the two MHC-peptide adducts H-2Ld +
      LSPFPFDL and H-2Kb + SIYRYYGL is mediated by the same TCR and appears to be
      similarly efficient as concluded from inhibition experiments with an Id-specific
      Ab. CTLs from SIYRYYGL-primed H-2b mice respond to H-2Ld + LSPFPFDL. This
      reciprocal cross-reactivity suggests that structural features are shared by the
      two MHC-peptide complexes.

PMID- 8752917
TI  - A novel population of CD4+CD56+ myelin-reactive T cells lyses target cells
      expressing CD56/neural cell adhesion molecule.
AB  - CD56 is a member of the neural cell adhesion molecule family expressed on cells
      of the central nervous system and also on NK cells. Previous studies suggest the
      involvement of CD56 in effector-to-target cell conjugation mediated by NK cells.
      It was shown recently that CD56 is also expressed by subpopulations of CD8+ and
      CD4+ T cells. The present study describes the functional characteristics of
      CD4+CD56+ T cell lines established from blood of multiple sclerosis patients by
      stimulation with myelin basic protein (MBP). CD4+CD56+, MBP-specific T cell lines
      were able to lyse MBP-pulsed target cells in an HLA class II-restricted fashion.
      At the same time, they mediated MHC-unrestricted lysis of CD56+ target cells such
      as CD56+ lymphoid or glial tumor cells, but not of the typical NK target, K562. A
      number of experimental results including separation of CD4+CD56+ T cells into
      CD56 high and low expressing populations, cold target inhibition, as well as
      killing of CD56-transfected cells indicate that homotypic CD56 interactions are
      involved in the MHC-unrestricted lysis. CD56 interactions are not sufficient but
      are required for effector/target interaction. Our findings raise the possibility
      that CD4+CD56+ T cells sharing properties of both typical Ag-specific Th0-like T
      cells and NK cells might be involved in damage of tissues expressing CD56/neural
      cell adhesion molecule, such as the central nervous system. Thus, we provide
      evidence for a novel mechanism that could lead to organ-specific autoreactivity.

PMID- 8752918
TI  - IL-12 is a central mediator of acute graft-versus-host disease in mice.
AB  - Distinct forms of graft-vs-host disease (GVHD) occur in (C57B1/6 x DBA/2)F1
      (BDF1) mice inoculated with either C57B1/6 or DBA/2 parental spleen cells, and it
      has been suggested that this reflects differential activation of CD4+ Th cell
      subsets. Transfer of B6 cells produces an acute GVHD, during which an early
      period of lymphoid hyperplasia precedes immunosuppression, weight loss, and
      mortality, and a Th1 pattern of cytokines is produced. Conversely, transfer of
      DBA/2 cells induces a chronic GVHD, in which no weight loss or mortality is
      observed, but an autoimmune, SLE-like GVHD develops in association with a Th2
      pattern of cytokines. Recent work indicates that IL-12 plays a central role in
      the polarization of Th cell-dependent responses, and here we have examined its
      role in polarizing GVHD, by administering or depleting IL-12 during the afferent
      phase of both the acute and chronic forms of GVHD in BDF1 mice. In vivo
      neutralization of endogenous IL-12 ameliorated acute GVHD, in association with
      reduced splenic NK cell activity, IFN-gamma production, immunosuppression, weight
      loss, and mortality. Conversely, administration of exogenous murine rIL-12
      exacerbates this disease and converts the chronic GVHD into a lethal acute GVHD
      like syndrome. These results indicate that IL-12 plays an important role in the
      development of acute, but not chronic, GVHD and suggest that differential
      production of IL-12 early in the disease may underlie these distinct outcomes of
      the GVHD in BDF1 mice injected with different parental cells.

PMID- 8752919
TI  - Specific inhibition of T lymphocyte coactivation by triggering integrin beta 1
      reveals convergence of beta 1, beta 2, and beta 7 signaling pathways.
AB  - T cell coactivation is a dynamic process subject to integrin-dependent positive
      and negative regulation. Costimulation of human peripheral blood T cells by CD3
      mAb OKT3 in conjunction with anti-alpha 4 has been shown to be down-regulated by
      the anti-beta 1.1 epitope-specific mAb 18D3. As expected, maximal costimulation
      induced by alpha 4-specific mAb L25 was inhibited (70%) by the addition of
      soluble mAb 18D3. Surprisingly, soluble mAb 18D3 inhibited maximal proliferation
      induced by the costimulatory alpha 4 beta 7-specific mAb ACT-1 by 40%, thus
      demonstrating that one integrin subfamily can regulate the activity of another.
      To determine whether mAb 18D3 could regulate more than alpha 4-associated
      integrin-mediated costimulation, non-alpha 4 integrins were tested. mAb 18D3
      inhibited maximal proliferation induced by alpha 4-specific mAb 3D6, and an alpha
      4-specific mAb 16. This clearly demonstrates that a variety of integrin
      costimulatory molecules (of the beta 1, beta 2, and beta 7 subfamilies) can be
      regulated negatively by mAb 18D3. To analyze the specificity of this negative
      regulation, other cell surface costimulatory molecules were tested for
      susceptibility to mAb 18D3. Although Abs specific for CD4, CD26, CD28, CD44,
      CD45RA, or CD45RO were sufficient to activate T cells when co-immobilized with
      anti-CD3 mAb, all were refractory to the inhibitory effects of mAb 18D3.
      Inhibition of T cell activation directly correlated with diminished IL-2
      production. This suggests that mAb 18D3 selectively regulates integrin-dependent
      T cell activation by delivering a negative effect at some common point utilized
      by various integrin subfamilies.

PMID- 8752921
TI  - Non-T cell-derived IL-4 plays an important role in IgE production induced by
      antigen resensitization and is resistant to FK506.
AB  - The present study investigates the role of non-T cell-derived IL-4 in IgE
      production. It is well known that IL-4 is generally produced by T cells and
      induces IgE production. We have demonstrated that non-T cells also produce IL-4
      in vivo by injection with Ag following passive sensitization of mice with IgE. In
      contrast to its known potent immunosuppressive effects on T cells, FK506 only
      partially inhibited IL-4 produced by non-T cells; therefore, FK506 was found to
      be a useful tool for identifying a cell source of IL-4 production. We used this
      observation to examine the role of non-T cell-derived IL-4 in IgE production. The
      production of a high titer of IgE was induced by priming BALB/c mice with Ascaris
      suum extract and further enhanced by secondary immunization. The IgE production
      in this model was dependent on IL-4, since both primary and secondary IgE
      production were completely suppressed by injection with anti-IL-4 Ab. Although
      primary IgE production was completely inhibited by FK506, secondary IgE
      production was not inhibited. Furthermore, IL-4 induction in plasma was only
      partially inhibited by FK506 when the A. suum extract-primed mice were
      resensitized with Ag. These results indicate that IL-4 produced by non-T cells
      plays a crucial role in secondary IgE production.

PMID- 8752920
TI  - Requirement of Fas(CD95), CD45, and CD11a/CD18 in monocyte-dependent apoptosis of
      human T cells.
AB  - Our previous studies demonstrated that upon activation, monocytes (Mo) were able
      to sensitize peripheral blood T (PBT) cells to apoptosis induced by treatment
      with PMA. However, it is unknown what gene products provide the death signal to
      the sensitized PBT cells and how activated Mo enable PBT cells to become
      susceptible to apoptosis. Here, we show that PBT cells, but not Mo, express
      functional Fas ligand upon treatment with PMA. Moreover, this Mo-dependent T cell
      apoptosis could be blocked by a Fas-Ig fusion protein, as well as by a nonlytic
      mAb against Fas molecule. These results strongly suggest involvement of Fas-Fas
      ligand interaction in the death of PBT cells. Unlike Fas-induced apoptosis,
      however, Mo-dependent T cell death was completely inhibited by overexpression of
      the Bcl-2 protein, and PMA alone was sufficient to trigger apoptosis in T cells
      when Mo were included in culture. Furthermore, anti-CD11a, anti-CD18, or anti
      CD45/CD45RA mAbs; could prevent PBT cells from death triggered by PMA plus Mo,
      suggesting that these Ags participate in the apoptotic process. The participation
      of CD45RA in the death of PBT cells was further demonstrated by the observation
      that the J45.01 cell line, a CD45-deficient variant of Jurkat cells, did not
      undergo apoptosis by this Mo-dependent mechanism. When transfected with cDNA
      encoding CD45RA, J45.01 cells acquired apoptotic response to PMA stimulation in
      the presence of Mo to a similar, but lesser, degree than normal Jurkat cells.

PMID- 8752922
TI  - Molecular mimicry between an immunodominant amino acid motif on the 47-kDa
      lipoprotein of Treponema pallidum (Tpp47) and multiple repeats of analogous
      sequences in fibronectin.
AB  - Molecular mimicry, resulting from structural similarities between self
      determinants on host Ags and an organism's antigenic determinants (epitopes), can
      incite autoimmune events in certain bacterial and viral diseases. In the course
      of comprehensively mapping the 47-kDa lipoprotein (Tpp47) of Treponema pallidum
      subsp. pallidum using an overlapping synthetic peptide strategy, we identified a
      major immunoreactive epitope (411PGTEYT416) that exhibited considerable motif
      identity with multiple repeats of analogous linear sequences found in mammalian
      fibronectins. To further explore the importance of this motif as a probable
      instigator in the induction of polyspecific cross-reactive Abs, mimetic variants
      were synthesized for immunologic studies. Mimetics with ala (A) replacements in
      each amino acid position were used to determine which residues were critical for
      Ab binding. Animals immunized with two mimetics (PGTEYT or PGSEYT) coupled to
      tetanus toxoid exhibited: 1) modified responses when challenged with viable T.
      pallidum; and 2) classical Arthus reactions when challenged intradermally with
      either motif linked to a different carrier. The cross-reactive nature of the Ab
      responses to both mimetics was confirmed in a variety of ELISAs using mimetics,
      fibronectins, and collagens. Inhibition-ELISA studies with both fibronectin and
      an unrelated mimetic of the RGD motif suggest that intra- and intermolecular
      epitope spreading occurs following mimetic immunization and involves additional
      self-epitopes. These observations suggest that although molecular mimicry plays a
      pivotal role in initially triggering the anti-fibronectin and anti-collagen
      responses associated with disseminated syphilis, expansion of those autoimmune
      responses may be due to other self-epitopes once tolerance is abrogated.

PMID- 8752923
TI  - High affinity antibodies against Lex and sialyl Lex from a phage display library.
AB  - Our previous studies of seven murine mAbs against the carbohydrate Lex Ag
      demonstrated that they were all encoded by VH441 and V kappa 24B. To obtain
      higher affinity Abs, and to ascertain whether their L chains could be encoded by
      other genes, we constructed a phage display library in a modified pComb 8 vector.
      The library contained random L chains, and Fd segments enriched in VH domains
      encoded by the VHX24 gene family. We selected phage with an Lex-BSA Ag, and
      obtained two Fab mAbs, clones 23 and 24, whose affinities were more than 100-fold
      higher than hybridoma mAb PM81. Both new mAbs were encoded by VH441, and their L
      chains were encoded by genes of the V kappa Ox1 and V kappa 9 families. In
      contrast to hybridoma mAb PM81, which binds only Lex, clones 23 and 24 bound
      sialyl Lex (SLex) as well as Lex, and clone 23 also binds the backbone
      carbohydrate structure nLacCer. Analysis of the binding of these three mAbs to
      synthetic glycolipids that contained structural modifications indicated that they
      recognize different aspects of the Lex structure, and suggested that they bind to
      limited regions of the oligosaccharide.

PMID- 8752924
TI  - Determinants of polyreactivity in a large panel of recombinant human antibodies
      from HIV-1 infection.
AB  - A considerable part of the Ab repertoire is given over to polyreactive Abs
      capable of interacting with multiple antigenic species. Neither the function of
      these Abs nor the molecular basis for their activity is known. To address the
      latter problem, we have compared the amino acid sequences of a large panel (n =
      70) of polyreactive human monoclonal Fab fragments and conducted a series of
      engineering experiments on a prototype polyreactive Fab. The Fab fragments were
      retrieved from combinatorial IgG libraries prepared from the bone marrow of long
      term asymptomatic HIV-1 seropositive donors. The general features displayed by
      the panel of IgG polyreactive Abs include 1) skewed VH family usage with a
      predominance of VH1 and VH4 clones and a paucity of the normally prevalent VH3
      family; 2) use of a variety of different VH germ-line genes within the context of
      the family usage and no restriction in D or JH gene usage; 3) skewed VL gene
      usage: 75% of Fabs used one of two germ lines; and 4) extensive somatic
      modification of both heavy and light chains. The importance of the heavy chain,
      in particular the heavy chain CDR3 (HCDR3), in dictating the polyreactive
      phenotype was demonstrated for the prototype Fab by chain shuffling and CDR
      transplantation experiments. in addition, and most strikingly, a constrained
      peptide based on the HCDR3 sequence was shown to be polyreactive and to inhibit
      binding of the parent Ab to a panel of Ags. A role for conformational flexibility
      in polyreactivity was suggested by a marked temperature dependence of Ab
      recognition of Ag. One Ab was shown to be polyreactive at 37 degrees C, but was
      apparently monoreactive at 4 degrees C. We hypothesize that Ab polyreactivity is
      associated with conformationally flexible HCDR3 regions in the context of certain
      favorable framework configurations.

PMID- 8752925
TI  - Lack of association of secretory component with IgA in J chain-deficient mice.
AB  - J chain has been proposed to play a role in the mucosal transport of polymeric
      Igs (pIg) by the polymeric Ig receptor (pIgR). We have previously reported the
      generation of J chain-deficient mice. These mice exhibited elevated serum IgA and
      depleted biliary and fecal IgA levels compared with wild-type mice. We report
      here that, unlike the IgA levels in bile and feces, IgA levels in local mucosal
      and glandular secretions were not depressed in J chain-deficient mice. Breast
      milk, intestinal mucosal surface, and nasal wash IgA levels in the mutant mice
      were similar to wild-type mice while bronchoalveolar lavage IgA levels were
      higher in the J chain-deficient animals. Western blot analysis with an Ab to
      secretory component (SC), the portion of the pIgR that remains bound to pig in
      secretions, and immunoprecipitation with Abs directed against IgA showed that
      secreted IgA was associated with SC in wild-type but not J chain-deficient mice.
      The IgA in wild-type secretions was polymeric while the secretions of J chain
      deficient mice contained IgA monomers and other nonpolymeric IgA forms. Thus, J
      chain is not essential for IgA transport by intestinal, mammary, or respiratory
      epithelia but is necessary for the stable association of pIgA with SC. Further,
      we suggest that J chain-deficient IgA is transported into secretions by a
      different mechanism than wild-type IgA.

PMID- 8752926
TI  - A negatively charged anchor residue promotes high affinity binding to the MHC
      class II molecule I-Ak.
AB  - An allele-specific peptide-binding motif for the murine MHC class II molecule I
      Ak has proven elusive. Here we demonstrate that the I-Ak molecule preferentially
      binds peptides that contain negatively charged amino acids at the primary anchor
      position (Asp or Glu at P1), and that I-Ak can also bind peptides with polar
      residues at P1 (Cys, Ser, Asn, Gin, or Thr), although with lower affinity. This
      preference for a negatively charged anchor residue is so pronounced that
      polyalanine peptides containing a single Asp can bind to I-Ak. Eight naturally
      processed peptides were found to use an Asp, as demonstrated by a drop in the I
      Ak binding affinity of these peptides after Ala substitution. The chemical
      identity of the amino acid in the anchor position was also important in
      determining the ability of peptide-I-Ak complexes to resist denaturation on SDS
      polyacrylamide gels. The P1 binding pockets of HLA-DR and H-2E molecules are
      reported to be large and hydrophobic, and these class II molecules prefer to bind
      peptides with large aliphatic or aromatic side chains at P1. Our results suggest
      that the structure of the I-Ak P1 binding pocket is different. Based on sequence
      comparisons, we suggest that the P1 binding pockets of H-2A molecules may prove
      more polymorphic than the P1 binding pockets of H-2E molecules, and that this
      additional polymorphism will cause H-2A molecules to display larger intra-allelic
      differences in peptide binding specificities.

PMID- 8752927
TI  - Somatically mutated B cell pool provides precursors for insulin antibodies.
AB  - Antibodies to insulin are products of autoreactive B lymphocytes that escape
      inactivation or clonal deletion and are examples of "clonal ignorance." To
      understand the genetic origin of Abs from clonally ignorant B cells, the roles of
      somatic mutation and germ-line V(H) structures were examined for two murine IgG1
      mAb that bind human and rodent insulin. Engineered mAb constructs that express
      germ-line or mutated V(H) genes show that somatic mutations introducing aspartic
      acid in or adjacent to CDRH2 play a key role in insulin binding. When either of
      the two anti-insulin V(H) regions is returned to its germ-line (unmutated)
      sequence, neither mAb binds insulin and the germ-line-encoded mAb are not
      polyreactive. Reconstruction of the somatic evolution of insulin binding in both
      mAbs shows that a single mutation in CDRH2 is sufficient to generate anti-insulin
      activity from a nonbinding precursor. When the role of somatic mutation in the
      binding of rodent insulin is examined, autoreactivity is associated with single
      mutations in both Abs. Together these findings indicate that, despite a low
      mutation frequency, IgG insulin Abs may not be derived directly from germ-line
      (unmutated) precursors. The requirement for somatic mutation as a prerequisite
      for measurable insulin binding suggests these Abs have their origin in a
      previously mutated B cell pool as a consequence of the individual's immune
      history. Low avidity interaction with endogenous insulin may play a role in
      selection of these B cells and contribute to the origin of clonal ignorance.

PMID- 8752929
TI  - Enhanced growth of murine melanoma in ultraviolet-irradiated skin is associated
      with local inhibition of immune effector mechanisms.
AB  - We have developed a model for studying the role of local immunologic mechanisms
      in tumor development, in which injection of K1735 melanoma cells into the UV
      irradiated ears of C3H mice results in a significantly higher incidence of tumors
      than injection into unirradiated ears. This effect of UV irradiation is
      immunologically mediated. We hypothesized that UV blocks the efferent arm of the
      immune response, thereby facilitating tumor development within the irradiated
      site. We demonstrate that elicitation of a delayed type hypersensitivity response
      to alloantigen is diminished in UV-irradiated ears. in addition, tumor rejection
      is impaired in melanoma-immune mice challenged in UV-irradiated ears, even though
      such mice exhibit systemic immunity when challenged in a nonirradiated site. The
      ability of immune lymphoid cells to inhibit melanoma growth when mixed with tumor
      cells and injected into the ears was inhibited by prior UV irradiation of the
      ears, indicating that the activity of immune effector cells is abrogated in the
      UV-irradiated microenvironment. Analysis of lymphoid cells in growing tumors
      indicated that the number of CD8+ T lymphocytes was reduced in the UV-irradiated
      site. We conclude that efferent immune responses are impaired in UV-irradiated
      tissue and suggest that the impairment may involve reductions in both the number
      and the activity of immune effector cells. These studies illustrate that
      conditions in the local microenvironment during the early stages of tumor growth
      may profoundly influence the outcome of the host-tumor interaction.

PMID- 8752928
TI  - Isolation of a neutralizing human RSV antibody from a dominant, non-neutralizing
      immune repertoire by epitope-blocked panning.
AB  - We isolated a large panel of human Abs directed against the respiratory syncytial
      virus (RSV) Ag from combinatorial phage display libraries. Following initial
      differentiation of the Fabs by BstNI restriction patterns, DNA sequence analysis
      revealed 10 different classes of VH paired with more than 35 different VL genes.
      All the Fabs bound with high affinity to the F Ag. However, most Fabs competed
      with the binding of a representative member of this group, suggesting that the
      Fabs recognized a common epitope on the F Ag, and none of them neutralized virus
      in vitro. To suppress repetitive isolation of these non-neutralizing Abs, a
      representative Fab was included during panning to block this common epitope on
      the F Ag. By this "epitope-blocked panning" approach, two novel Fabs, encoded by
      unique VH and VL genes, were isolated from a previously screened library.
      Competition binding analysis confirmed that the Fabs recognized epitopes distinct
      from that of the previously isolated Fabs. One of these Fabs, 516, neutralized
      RSV in cell culture. These activities of Fab-516 were retained upon its genetic
      conversion to a mAb (IgG1) and expression in mammalian cells. Our results suggest
      that the RSV F glycoprotein presents a dominant, non-neutralizing epitope to the
      human immune system, which may serve in evasion of host defenses. However, less
      prevalent, fusion-inhibiting Abs were revealed by blockade of this epitope during
      the panning process.

PMID- 8752930
TI  - Multiple HLA-A alleles can present an immunodominant peptide of the human
      melanoma antigen Melan-A/MART-1 to a peptide-specific HLA-A*0201+ cytotoxic T
      cell line.
AB  - The majority of HLA-A*0201-restricted tumor-infiltrating lymphocytes from
      melanoma patients recognize a peptide, MT(27-35), derived from the Melan-A/MART-1
      Ag. This study reports that six variants of HLA-A2 and the HLA-A28 subtype A*6901
      can present peptide MT(27-35). A CTL line specific for peptide MT(27-35) was
      generated by in vitro stimulation of PBL of an HLA-A*0201+, healthy donor with
      peptide-pulsed, activated autologous B lymphoblasts. This CTL line was shown to
      recognize peptide MT(27-35) after endogenous processing on Melan-A/MART-1+/HLA
      A2+ tumor cells. Moreover, a panel of B lymphoblastoid cell lines (BLCLs)
      expressing A*0202, A*0204, A*0205, A*0206, A*0209, and with lower efficiency
      A*6901, could be sensitized to lysis upon incubation with the relevant peptide.
      As demonstrated by the levels of ED50 and CD8 dependency of lysis, HLA-A*0204 and
      HLA-A*0205 presented the peptide as efficiently as HLA-A*0201, while the other
      four alleles were less efficient. Peptide-binding studies suggest that TCR-
      rather than peptide-binding affinity determines the T cell recognition levels of
      peptide-pulsed EBV-BLCLs expressing A*0201, A*0204, A*0206, and A*0209. Peptide
      pulsed BLCLs expressing HLA-A*0207 or two additional subtypes of HLA-A28 were not
      recognized. MT(27-35)-specific CTL could also be raised from donors expressing
      HLA-A*0205. These findings have implications on the applicability of peptide
      vaccination with peptide MT(27-35) on melanoma patients.

PMID- 8752931
TI  - In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii
      succumb to a lethal immune response dependent on CD4+ T cells and accompanied by
      overproduction of IL-12, IFN-gamma and TNF-alpha.
AB  - To examine the function of IL-10 synthesis during early infection with the
      intracellular protozoan Toxoplasma gondii, IL-10 knockout (KO) mice were
      inoculated with an avirulent parasite strain (ME-49). In contrast to control
      littermates that displayed 100% survival, the IL-10-deficient animals succumbed
      within the first 2 wk of the infection, with no evidence of enhanced parasite
      proliferation. The mortality in the IL-10 KO mice was associated with enhanced
      liver pathology characterized by increased cellular infiltration and intense
      necrosis. Levels of IL-12 and IFN-gamma in sera of infected IL-10-deficient
      animals were four- to sixfold higher than those in sera from control mice, as
      were mRNA levels for IFN-gamma, IL-1 beta, TNF-alpha, and IL-12 in lung tissue.
      Similarly, macrophages from IL-10 KO mice activated in vitro or in vivo with T.
      gondii produced higher levels of TNF-alpha and IL-12 than macrophages from
      control animals. Moreover, spleen cells from IL-10 KO mice infected with T.
      gondii secreted more IFN-gamma than splenocytes from nondeficient animals. In
      vitro depletion experiments indicated that CD4+ lymphocytes are the major source
      of the latter cytokine in the spleen cell populations, and in vivo depletion with
      anti-CD4 Abs protected the IL-10 KO mice from parasite-induced mortality.
      Together the data suggest that endogenous IL-10 synthesis plays an important role
      in vivo in down-regulating monokine and IFN-gamma responses to acute
      intracellular infection, thereby preventing host immunopathology.

PMID- 8752932
TI  - Calpain is the target antigen of a Th1 clone that transfers protective immunity
      against Schistosoma mansoni.
AB  - A CD4+ clone (clone B), characterized as Th1 based on its selective production of
      IFN-gamma and IL-2, was established from C57Bl/6 mice protectively immunized
      against Schistosoma mansoni by intradermal vaccination with soluble worm Ags,
      plus bacillus Calmette Guerin. In agreement with previous results demonstrating
      an IFN-gamma-dependent cell-mediated protective mechanism in this vaccination
      model, Ag-elicited peritoneal macrophages from syngeneic recipients of this clone
      were activated to kill schistosome larvae (schistosomula) in vitro. Moreover,
      recipients of clone B displayed significant resistance against cercarial
      challenge. By screening a battery of lambda(gt11) clones from an adult worm cDNA
      library, one recombinant (25B) was identified that stimulated clone B
      specifically. Analysis of the 25B cDNA insert revealed a nucleotide sequence
      identical with that of the large subunit of schistosome calpain, a Ca2+-activated
      neutral proteinase. By expressing the products of PCR subcloning, we identified a
      146-amino acid region of the 25B gene containing immunologic activity equivalent
      to the whole polypeptide. Overlapping peptides spanning this region were
      synthesized, and a core epitope was identified with the sequence EWKGAWCDGS.
      Since clone B responds to supernatants from cultured schistosomula, we postulate
      that the recognition of calpain released by invading larvae and resulting
      induction of Th1 cytokines accounts for the protection mediated by the adoptively
      transferred clone. Our findings thus implicate calpain as a target of protective
      immunity in schistosomes and provide the first example of a candidate vaccine Ag
      for this parasite identified on the basis of T cell reactivity.

PMID- 8752933
TI  - Exacerbated viral hepatitis in IFN-gamma receptor-deficient mice is not
      suppressed by IL-12.
AB  - Both IL-12 and IFN-gamma have been implicated as principal inducers of type 1
      immune responses required for the elimination of intracellular pathogens, such as
      viruses. We examined the in vivo antiviral role of both cytokines during
      coronavirus-induced hepatitis in a mouse hepatitis virus (MHV) model. The absence
      of IFN-gamma function in mice with a targeted disruption of the IFN-gamma R alpha
      chain gene (IFN-gamma R -/-) resulted in increased susceptibility to coronaviral
      hepatitis associated with augmented viral replication and increased
      hepatocellular injury. The mutant mice showed a type 1 lymphokine response
      characterized by the normal high IFN-gamma and low IL-4 production. Unlike MHV
      infected wild-type mice, however, the mutant IFN-gamma R -/- mice showed no
      increase in IL-12 p4O gene expression, similar to that in naive animals. IL-12
      treatment failed to restore host resistance in IFN-gamma R -/- mice, but
      significantly protected MHV-susceptible C57BL/6 mice against lethal infection,
      although less than IFN-gamma treatment. Mice protected by IL-12 or IFN-gamma
      showed resistance against an otherwise lethal second MHV infection. Our data
      demonstrate that despite reduced IL-12 gene expression and defective IFN-gamma R
      function, virus-induced IFN-gamma production can occur. Furthermore, they
      emphasize the pivotal antiviral role of IFN-gamma in protection against acute
      coronavirus-induced hepatitis.

PMID- 8752934
TI  - Recombinant polyepitope vaccines for the delivery of multiple CD8 cytotoxic T
      cell epitopes.
AB  - Development of epitope-based CD8 alpha beta CTL vaccines requires effective
      strategies for codelivery of large numbers of individual epitopes. We have
      designed an artificial "polyepitope" protein containing 10 contiguous minimal CTL
      epitopes, which were restricted by five MHC alleles and derived from five
      viruses, a parasite, and a tumor model. A recombinant vaccinia virus coding for
      this protein was capable of inducing MHC-restricted primary CTL responses to all
      10 epitopes. Mice immunized with this recombinant vaccinia showed protection
      against murine cytomegalovirus, Sendai virus, and a tumor model. This simple
      generic approach to multiepitope delivery should find application in CTL-based
      vaccine design.

PMID- 8752935
TI  - Mice lacking the TNF receptor p55 fail to resolve lesions caused by infection
      with Leishmania major, but control parasite replication.
AB  - TNF is involved in host resistance to several pathogens. Recently it was found
      that mice lacking the p55 receptor for TNF (TNFRp55 -/-) do not control growth of
      the intracellular bacteria, Listeria monocytogenes and Mycobacterium
      tuberculosis. Here we report that the course of infection in TNFRp55 -/- mice
      with another intracellular pathogen, the protozoan parasite Leishmania major, is
      also quite different from normal mice. TNFRp55 -/- mice developed larger lesions
      than control mice and failed to resolve these lesions. However, they were able to
      eliminate parasites within the lesions. Histologic analysis indicated that at
      late stages lesions from TNFRp55 -/- mice appeared similar to lesions associated
      with cutaneous graft-vs-host disease. Both TNFRp55 -/- and control mice developed
      a normal Th1-type response during infection. We also found that IFN-gamma
      activated macrophages from TNFRp55 -/- mice produced nitric oxide and killed L.
      major in vitro, which correlated with the ability of TNFRp55 -/- mice to
      eliminate the parasites in vivo. The production of nitric oxide by macrophages
      from TNFRp55 -/- mice required the presence of the parasites, however, since in
      their absence TNF could only synergize with IFN-gamma for nitric oxide production
      when added to normal, but not TNFRp55 -/-, macrophages. These results indicate
      that neither macrophage microbicidal activity nor nitric oxide production is
      absolutely dependent on the p55 receptor for TNF. Furthermore, they uncover a
      previously undefined role for TNFRp55 in resolution of parasite-induced
      inflammatory lesions.

PMID- 8752936
TI  - Single chain Ig/gamma gene-redirected human T lymphocytes produce cytokines,
      specifically lyse tumor cells, and recycle lytic capacity.
AB  - To enable construction of CTL with known predefined Ab specificity for adoptive
      immunotherapy, we constructed a chimeric scFv/gamma gene composed of the variable
      regions of a mAb joined to the Fc(epsilon)RI signaling receptor gamma-chain of
      mast cells. Introduction of this chimeric receptor into CTL rendered these
      lymphocytes specific for renal cell carcinoma. This approach combines the
      specificity of tumor-selective Abs with the efficacy of CTL to destroy tumor
      cells. We not only demonstrated that the transduced CTL functionally express the
      scFv/gamma receptor for a prolonged period of time (4.5 mo of in vitro culture),
      but also showed high levels of Ab-dictated lysis of renal cell carcinoma similar
      to that of normal CTL, and importantly, we demonstrated that these CTL can
      recycle their lytic activity. Moreover, these scFv/gamma-expressing T lymphocytes
      produce cytokines upon stimulation with the relevant target cell. These results
      together with the donor independence of our gene transduction protocol
      demonstrate the feasibility of redirecting T lymphocytes for cancer treatment.

PMID- 8752937
TI  - Counter-receptors on human basophils for endothelial cell adhesion molecules.
AB  - Ligands on human basophils for the endothelial adhesion molecules intercellular
      adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), mucosal
      addressin cell adhesion molecule-1 (MAdCAM-1), and E-selectin were investigated.
      Adhesion of basophils to endothelial cells was inhibited by mAb recognizing CD18,
      CD11a, and/or CD11b, with the pattern and magnitude of inhibition dependent upon
      the activation state of the basophils and endothelium. Adhesion to recombinant
      VCAM-1 was completely inhibited by mAb recognizing alpha 4 integrin and partially
      by mAb to the beta 1 or beta 7 subunit; surface expression of these integrins was
      also detected. Adhesion to recombinant MAdCAM-1 expressed on Chinese hamster
      ovary cells was completely inhibited by mAb recognizing alpha 4 and/or beta 7
      integrins. Adhesion to recombinant E-selectin was completely inhibited by
      basophil pretreatment with neuraminidase and partially inhibited by endo-beta
      galactosidase. By flow cytometry, bimodal patterns of expression of sialyl-Lewis
      X- and sialyl-dimeric-Lewis X were observed, and adherent cells tended to be
      sialyl-dimeric-Lewis X positive. Thus, basophils express beta 1, beta 2, and beta
      7 integrins along with sialylated surface ligands that may interact with the
      endothelium during basophil recruitment responses.

PMID- 8752938
TI  - Human fibroblasts express functional IL-2 receptors formed by the IL-2R alpha-
      and beta-chain subunits: association of IL-2 binding with secretion of the
      monocyte chemoattractant protein-1.
AB  - Expression of IL-2R was examined on human fibroblasts isolated from different
      tissues. By specific binding assay it is shown that [125I]IL-2 bound to
      subconfluent adult bone marrow and embryonic skin and lung fibroblasts. The
      presence of binding sites for IL-2 was also confirmed by immunofluorescence and
      flow cytometry analysis using mAbs specific for the p55 IL-2R alpha (anti-CD25),
      p75 IL-2R beta, and p64 IL-2R gamma subunits. Fibroblasts also constitutively
      transcribed the genes coding for IL-2R alpha and IL-2R beta and accumulated their
      respective mRNAs but failed to exhibit the IL-2R gamma-chain on the mRNA and
      protein level. Although addition of IL-2 to fibroblast cultures did not
      significantly alter growth kinetics of these cells, the IL-2R complex displayed
      by fibroblasts appeared to be functional in that addition of IL-2 to these cells
      led to enhanced expression of the JE gene coding for the monocyte chemoattractant
      protein-1 (MCP-1). Enhancement of fibroblast MCP-1/JE gene expression by IL-2
      appeared to result from delayed MCP-1/JE mRNA decay rather than as a consequence
      of an acceleration of the MCP-1/JE gene transcription rate. IL-2 had, however, no
      effect on the expression of other cytokine genes including IL-1, IL-5, IL-6, IL
      7, IL-8, IL-9, granulocyte-macrophage-CSF, macrophage-CSF or TNF. These
      observations suggest that the range of cellular targets of IL-2 is broader than
      originally appreciated. IL-2 may thus serve to integrate fibroblasts and
      monocytes into a coordinated response of the connective tissue initiated by T
      lymphocytes.

PMID- 8752939
TI  - Neutrophil adhesion to 24-hour IL-1-stimulated endothelial cells under flow
      conditions.
AB  - In this study, we examine neutrophil adhesion under flow conditions to cultured
      HUVEC stimulated for 4 or 24 h with IL-1. Interactions are measured using
      videomicroscopy and a parallel-plate flow system which is capable of
      distinguishing primary adhesion and rolling from secondary (firm) adhesion. We
      find that after 24 h, E-selectin does not contribute to primary adhesion, in
      contrast to a significant contribution after 4 h. Endothelial cell P-selectin
      does not contribute at either time point. Blocking or removing L-selectin from
      the neutrophil surface decreases adhesion 50 to 70% at either time point, and
      neuraminidase treatment of neutrophils decreases adhesion by 85%. These results
      suggest that after a 24-h stimulation, primary adhesion depends on a distinct
      selectin-like interaction in which a HUVEC receptor binds carbohydrates on
      neutrophil glycoproteins, including L-selectin. We also find that secondary
      adhesion in this system can be inhibited 90% with Ab blockade of CD18/ICAM-1
      interactions after a 24-h stimulation, and that a combination of IL-1 and IL-4
      selectively down-regulates the pathway for primary adhesion at 24 h. These
      results demonstrate that neutrophils adhere using different receptor pathways
      following 4- and 24-h stimulations, and provide experimental data characterizing
      some properties of the receptors involved. One of the pathways that is evident at
      24 h appears to be a novel selectin-like interaction.

PMID- 8752940
TI  - IFN-gamma-induced MHC class II gene expression is suppressed in endothelial cells
      by dextran sulfate.
AB  - IFN-gamma-activated endothelial cells actively participate in initiating immune
      responses by interacting with immunocompetent cells via class II MHC proteins. In
      this study, dextran sulfate, a synthetic heparin analogue, was shown to
      selectively inhibit IFN-gamma-induced surface expression of HLA-DR molecules by
      human umbilical cord vascular endothelial cells, but not other cytokine-induced
      molecules such as ELAM-1 or ICAM-1. Inhibition occurred regardless of whether
      dextran sulfate was added 24 h before, at the same time as, or 24 h after IFN
      gamma stimulation of cells. In addition, both high (500 kDa) and low (5 kDa)
      molecular mass dextran sulfate molecules were able to block class II expression,
      whereas treating cells with naturally occurring polysulfated glycosaminoglycans
      such as heparin, heparan, and chondroitin sulfate did not produce any suppressive
      effects. Radiolabeling of cells with [35S]methionine followed by
      radioimmunoprecipitation using anti-HLA-DR alpha mAb demonstrated that
      biosynthesis of class II proteins was specifically blocked. RT-PCR and Southern
      blotting were utilized to examine transcription of the HLA-DR alpha gene and
      demonstrated an absence of HLA-DR alpha mRNA from dextran sulfate-treated and IFN
      gamma-induced cells. Dextran sulfate also prevented transcription of the gene
      encoding CIITA, a transactivator protein required for IFN-gamma-inducible
      expression of class II genes. Thus, dextran sulfate apparently inhibited this
      step or an earlier one in the intracellular signaling pathway for IFN-gamma in
      human endothelial cells, subsequent to IFN-gamma binding to its cell surface
      receptor.

PMID- 8752941
TI  - Human Thy-1 is cytokine-inducible on vascular endothelial cells and is a
      signaling molecule regulated by protein kinase C.
AB  - Thy-1 is a glycosylphosphatidylinositol-anchored member of the Ig superfamily
      whose function, particularly in the human, remains unknown. We have demonstrated
      that human Thy-1 is expressed on endothelial cells (EC) both in situ and on the
      surface of cultured human umbilical vein EC and dermal microvascular EC (DMEC).
      The expression of the molecule decreased with serial passage but was restored by
      treatment of EC with PMA and phorbol-12,13-dibutyrate (PBu), which increased Thy
      1 by up to 100-fold in a dose-dependent manner. This increase was first
      detectable at 12 h post-stimulation, peaked at 48 h, and was maintained at 72 h.
      In PBu-stimulated DMEC, Western blotting revealed Thy-1 to be a 29-kDa molecule,
      while Northern analysis demonstrated an increase in steady-state Thy-1 mRNA. Thy
      1 expression was also induced on DMEC by treatment with TNF. Inhibition studies
      showed that the induction of Thy-1 by PBu and TNF was protein synthesis
      dependent. The up-regulation of Thy-1 by PBu, but not TNF, was inhibited by the
      protein kinase C inhibitor RO31-8220, suggesting the presence of protein kinase C
      dependent and -independent pathways for Thy-1 expression. To investigate the
      function of Thy-1 on human EC, we studied changes in intracellular calcium
      concentration ([Ca2+]i) following cross-linking of Thy-1 on human umbilical vein
      EC. This resulted in a rapid transient rise of [Ca2+]i in EC. Our results
      demonstrate for the first time the presence of Thy-1 on cultured human EC. The
      expression on EC, the inducibility by TNF, and the ability to transmit signals
      suggest that Thy-1 may have an important role in inflammatory responses.

PMID- 8752942
TI  - Inhibition of human complement by a C3-binding peptide isolated from a phage
      displayed random peptide library.
AB  - We have screened a phage-displayed random peptide library for binding to C3b, the
      proteolytically activated form of complement component C3, and have identified a
      novel peptide that suppresses complement activation. This phage-displayed peptide
      bound to C3, C3b, and C3c, but not to C3d, indicating that it binds to the C3c
      region of C3. A synthetic 27-amino acid peptide corresponding to the phage
      displayed peptide also bound to C3 and C3 fragments and inhibited both the
      classical and alternative pathways of complement activation. The inhibition of
      complement activation was reversible. Studies with overlapping peptides indicated
      that the functional activity was located in the cyclic 13-amino acid N-terminal
      region (ICVVQDWGHHRCT) of the parent peptide. Reduction and alkylation of this 13
      residue synthetic peptide destroyed its inhibitory activity. Analysis of the
      mechanism of inhibition revealed that the peptide inhibited C3 cleavage in normal
      human serum as well as when the alternative pathway was reconstituted with
      purified complement components, and the observed inhibition was not due to
      sterically hindered access to the C3a/C3b cleavage site. Further, the peptide did
      not inhibit the cleavage of factor B, indicating that it did not affect the
      interaction of CA with factor B or the formation of C3b,Bb. The peptide also had
      no effect on the binding of properdin to C3, demonstrating that the observed
      inhibition of C3 cleavage in normal human serum was not due in part to its effect
      on the properdin-stabilized C3 convertase, C3b,Bb,P. These results indicate that
      the peptide we have identified interacts with C3 to inhibit its activation.

PMID- 8752943
TI  - Stimulus-specific inhibition of intracellular adhesion molecule-1 gene expression
      by TGF-beta.
AB  - Astrocytes and microglia, the two major glial cells within the central nervous
      system, can function as immune effector cells upon activation. Intercellular
      adhesion molecule-1 (ICAM-1), a cell surface glycoprotein involved in
      extravasation into inflamed tissue and Ag-specific activation of T lymphocytes,
      can be induced in astrocytes and microglia by numerous stimuli. In this study, we
      investigated the role of TGF-beta, an immunosuppressive cytokine, in regulating
      ICAM-1 expression in glial cells. We previously demonstrated that TNF-alpha, IL-1
      beta, IFN-gamma, or IFN-gamma plus LPS (IFN-gamma/LPS) can enhance ICAM-1
      expression in astrocytes, while microglia express ICAM-1 only in response to IFN
      gamma or IFN-gamma/LPS. TGF-beta alone has a minimal effect on constitutive ICAM
      1 expression in either astrocytes or microglia, but inhibits, in a time-dependent
      manner, TNF-alpha- or IL-1 beta-induced ICAM-1 mRNA and protein expression in
      astrocytes. Interestingly, TGF-beta has no effect on IFN-gamma- or IFN-gamma/LPS
      induced ICAM-1 expression in astrocytes or microglia. Inhibition of TNF-alpha- or
      IL-1 beta-induced ICAM-1 mRNA levels by TGF-beta in astrocytes was not due to
      degradation of ICAM-1 message, rather, inhibition was mediated at the
      transcriptional level. Similar results were observed in two human astroglioma
      cell lines, CRT and STT; TGF-beta inhibited TNF-alpha- and IL-1 beta-induced ICAM
      1 expression, but IFN-gamma induction of ICAM-1 was unaffected. These results
      indicate that TGF-beta suppresses ICAM-1 expression in glial cells in a stimulus
      specific manner.

PMID- 8752944
TI  - Accelerated amyloid deposition in mice treated with the aspartic protease
      inhibitor, pepstatin.
AB  - The development of amyloidotic diseases is believed to be determined in large
      part by the structure and metabolism of the amyloid subunit protein. The amino
      terminal region of serum amyloid A (SAA), the subunit precursor protein in
      reactive amyloidosis, appears to confer fibrillogenic potential. Here we present
      data consistent with the hypothesis that amyloid A fibrillogenesis is favored
      when proteolysis of the amino-terminal region of SAA is impaired. Murine tissue
      extracts were found to contain pepstatin-inhibitable protease activity that
      cleaved mouse SAA2 between Glu8 and Ala9. Tissues obtained from mice that had
      been treated with pepstatin for 3 days lacked this activity. To investigate a
      possible relationship between inhibition of aspartic proteases and
      amyloidogenesis, mice were treated with pepstatin while concurrently undergoing a
      standard amyloid induction protocol (repeated casein injections). Pepstatin
      treated mice showed amyloid deposition significantly sooner than the control
      group, which had received only casein. During the preamyloidotic phase, pepstatin
      treated mice had higher concentrations of SAA in serum and spleen than control
      mice. In addition, clearance of injected 125I-labeled SAA from plasma was
      significantly delayed. Based on these findings, it is reasonable to postulate
      that inhibition of aspartic protease activity can lead to an accumulation of
      amino-terminally intact SAA molecules and thereby accelerate amyloid fibril
      formation.

PMID- 8752946
TI  - Analysis of the fine B cell specificity during the chronic/relapsing course of a
      multiple sclerosis-like disease in Lewis rats injected with the encephalitogenic
      myelin oligodendrocyte glycoprotein peptide 35-55.
AB  - We have recently shown that a single injection of myelin oligodendrocyte
      glycoprotein (MOG), or the MOG35-55 peptide, produces a relapsing-remitting
      neurologic disease with extensive plaque-like demyelination. Given the features
      that this new autoimmune demyelinating model has in common with the
      clinicopathologic manifestations of multiple sclerosis, we have examined the Ab
      reactivity to native MOG and MOG35-55 peptide during the course of the disease in
      Lewis rats. Following immunization with MOG35-55, varied clinical symptoms were
      observed; these included hind and foreleg paralysis and various degrees of
      balance impairment. Disease progression also varied: 3 out of 21 animals had a
      single mild disease episode; 4 out of 21 had a mild relapsing-remitting disease;
      and 14 out of 21 had severe relapsing-remitting disease. Ab reactivity to MOG35
      55 and native MOG was first detected in all rats 4 wk postimmunization and
      persisted throughout the 12 wk of observation. The Ab response was highly
      restricted with no reactivity to other peptides encompassing different
      extracellular segments of MOG. Fine epitope mapping showed that Ab from serum and
      cerebrospinal fluid of injected rats reacted strongly to MOG37-46 and to a lesser
      extent to MOG43-50. Although significant levels of anti-MOG Abs appeared
      necessary for the development of demyelinating lesions, their presence in blood
      and cerebrospinal fluid alone was not sufficient to produce severe clinical
      symptoms. These results demonstrate that the MOG35-55 peptide is highly
      encephalitogenic and can induce strong T and B cell responses. It is probably the
      complex interaction between these T and B cells that determines the severity of
      disease in individual rats.

PMID- 8752945
TI  - Role of IL-15, IL-2, and their receptors in the development of T cell alveolitis
      in pulmonary sarcoidosis.
AB  - Recent data suggest that the newly discovered cytokine IL-15 cooperates with IL-2
      in driving T cell-mediated immune responses. The aim of this study was to
      determine the role of IL-15 in the regulatory networks leading to the development
      of T cell alveolitis in the lung of patients with sarcoidosis. We demonstrated
      that alveolar macrophages (AMs) isolated from the bronchoalveolar lavage of
      patients with active sarcoidosis expressed IL-15 mRNA and membrane and
      cytoplasmic IL-15, while AMs from healthy subjects and patients with inactive
      sarcoidosis did not. Pulmonary CD4+ T cells from sarcoid patients were equipped
      with the IL-2R subunits, which are able to bind IL-15, i.e., the IL-2R beta/IL-2R
      gamma complex, and proliferated in response to IL-15. Interestingly, the T cell
      proliferation elicited by IL-15 was comparable with that determined by IL-2.
      Following the addition of graded amounts of IL-15, IL-2-pulsed T cells showed a
      significant increase in their stimulation. TNF-alpha up-regulated the IL-15
      mediated proliferative response of bronchoalveolar lavage T lymphocytes.
      Following the block of the IL-2R beta- and gamma-chains with specific mAbs, the
      stimulatory activity of IL-15 was abolished. The evaluation of the IL-2R on
      sarcoid AMs demonstrated the constitutive expression of alpha- and gamma-chain
      mRNA and proteins. Taken together, these findings demonstrate that IL-15 triggers
      the growth of sarcoid T cells through the IL-2R beta/IL-2R-gamma complex and
      raise the possibility that AMs may deliver proliferative signals for the
      development of the T cell alveolitis. Modulation of IL-2R on AMs could represent
      a critical variable in regulating local inflammatory responses.

PMID- 8752948
TI  - IL-10 modulates formation of osteoclasts in murine hemopoietic cultures.
AB  - IL-10, originally described as a cytokine synthesis inhibitory factor produced by
      T cells, has recently been found to suppress osteoblastic differentiation in
      mouse bone marrow cultures. Since osteoblastic cells exert a major influence on
      the production and regulation of osteoclasts, the cells that resorb bone, this
      suggests that the cytokine might play a role in the regulation of bone
      resorption. We, therefore, tested the actions of the cytokine on osteoclast
      formation and function. We found no effect of IL-10 on the resorptive function of
      mature osteoclasts, either when isolated or when incubated in the presence of
      osteoblastic cells. However, IL-10 suppressed bone resorption in bone marrow
      cultures and in cocultures of bone marrow stromal cell lines with hemopoietic
      spleen cells. In both systems, suppression of bone resorption was associated with
      a substantial reduction in the ratio of calcitonin receptor-positive cells to
      macrophages, suggesting that IL-10 exerts a reciprocal action on the
      differentiation of osteoclasts and macrophages from their shared precursor. This
      reciprocal action is very similar to that associated with the addition of
      macrophage CSF to hemopoietic cultures, and we found that IL-10 increased the
      expression of mRNA for macrophage CSF in bone marrow cultures. This potent
      inhibition of osteoclast formation by IL-10 suggests that IL-10 might play a role
      in the modulation of bone loss in inflammatory disorders.

PMID- 8752947
TI  - Cloning and analysis of IgG kappa and IgG lambda anti-thyroglobulin
      autoantibodies from a patient with Hashimoto's thyroiditis: evidence for in vivo
      antigen-driven repertoire selection.
AB  - Antibodies to thyroglobulin (Tg) are commonly found in patients with the
      autoimmune thyroid diseases Graves' disease and Hashimoto's thyroiditis as well
      as in individuals with apparently normal thyroid function. Although it is not
      clear how Tg Abs are involved in the pathology of the diseases, the study and
      analysis of these Abs may nevertheless be instructive in allowing the development
      of an Ab response to an autoimmune disease-associated self Ag to be followed. We
      have prepared IgG kappa and lambda phage display combinatorial libraries from the
      cervical lymph node of a single Hashimoto's thyroiditis patient with a high anti
      Tg titer. These were selected with purified human Tg, and 10 IgG kappa and 9 IgG
      lambda clones were analyzed further. Sequence analysis of the clones showed a
      very highly restricted heavy chain usage and a less restricted light chain usage.
      There was a variable degree of divergence from germ-line sequence in the light
      chain sequences, with a clear relationship between relatively higher affinity of
      the Fab for human Tg and an increased degree of somatic hypermutation. The Tg
      selected Fab did not bind to Tg from other species, to reduced denatured Tg, or
      to thyroid peroxidase. The Fab inhibited patient serum binding to human Tg by
      between 39 and 79%. In summary, we have isolated 19 high affinity, human Tg
      specific Fab and shown that the relative affinity of the Fab is directly related
      to the pattern of somatic hypermutation.

PMID- 8752949
TI  - A pathogenic role for gamma delta T cells in relapsing-remitting experimental
      allergic encephalomyelitis in the SJL mouse.
AB  - Previous studies have detected gamma delta T cells in multiple sclerosis and
      experimental allergic encephalomyelitis (EAE) lesions but their role remains
      obscure. In the present study, we assessed gamma delta T cell dynamics and
      distribution in spleen and central nervous system (CNS) from mice with relapsing
      remitting EAE, and studied the effect of depleting these cells on clinical and
      pathologic expression of disease using the mAb GL3. By immunohistochemistry and
      FACS analysis, striking disease-related changes were observed in the gamma delta
      T cell population in the CNS. FACS analysis showed that while gamma delta T cells
      remained low in the spleen (approximately 2% total CD3+ T cells) at all stages,
      in the CNS they increased to approximately 12% at the height of the acute attack,
      fell to approximately 5% during the recovery phase, but rose again to
      approximately 12% during the chronic phase. In animals in which gamma delta T
      cells were depleted immediately before the onset of acute disease, or during the
      chronic stage, a striking and significant reduction in the severity of the
      clinical signs was observed that was associated with a decrease in the percentage
      of CD3+/gamma delta T cells in the CNS. In depleted animals a statistically
      significant reduction in inflammation and demyelination was noted during the
      acute stage, but only marginal effects on these disease parameters were found in
      the chronic phase. Taken together, the data support the conclusion that gamma
      delta T cells play an important role in the pathogenesis of EAE in mice during
      both acute and chronic/progressive phases of the disease process.

PMID- 8752950
TI  - Human IgG production in vivo: determination of synthetic rate by nonradioactive
      tracer incorporation.
AB  - Exposure of Ab-secreting cells to selected hormones, cytokines, and drugs alters
      the rate of Ig production in vitro. Whether these effects are important
      clinically is unknown because there are no safe, reproducible, and appropriate
      techniques for measuring Ig synthesis in vivo. We developed a stable isotope
      tracer method to measure IgG secretion into plasma. L-[1-13C]Leucine was given as
      a priming dose followed by a constant i.v. infusion over 8 h. Tracer accrual in
      IgG, determined by mass spectrometry, was linear from 2 to 8 h of the infusion.
      The normal rate of IgG synthesis into plasma assessed in 21 healthy subjects was
      860 +/- 310 mg/day (mean +/- SD). The synthetic rate measurements were remarkably
      reproducible (coefficient of variation = 10.5 %). Simultaneous analysis of
      leucine kinetics allows, for the first time, Ig secretion to be studied in the
      context of whole body protein economy. IgG secretion into plasma accounts for
      0.3% of whole body protein synthesis. Experimental support for a key metabolic
      assumption, that tracer enrichment in plasma and that at the site of IgG
      synthesis were similar, came from a comparison of synthetic rates derived from
      low dose and high dose tracer infusions. Measurement of Ig secretion by tracer
      incorporation is rapid and reproducible. In contrast to older methods that rely
      on radioisotope disappearance, the tracer incorporation method is safe for serial
      measurements in an individual and will be useful for quantitative studies of
      treatment effects and immune regulation in vivo.

PMID- 8752951
TI  - Human IgG monoclonal antibodies that modulate the binding of specific IgE to
      birch pollen Bet v 1.
AB  - Birch pollen allergy is a very frequent pathology in Europe and North America.
      More than 95% of the tree pollen allergic patients display IgE reactivity against
      Bet v 1, the major birch pollen allergen. Starting with PBL from a patient
      desensitized by immunotherapy, we have generated five B cell lines (BAB1 to BAB5)
      that secrete human IgG mAbs of high affinity for Bet v 1. Although competition
      studies indicated that these human IgG mAb recognized different epitopes, broad
      cross-reactivity was found with Bet v 1 homologous allergens present in tree
      pollens and plant-derived foods. When tested for interference with allergic
      patients' IgE, BAB1 inhibited (by 80-100%) the binding of IgE to nitrocellulose
      blotted Bet v 1, while BAB2 enhanced it. The biologic significance of the ability
      of BAB1 to interfere with patients' IgE binding is indicated by the finding that
      BAB1 completely inhibited Bet v 1-induced histamine release from allergic
      patients' basophils. Allergen-specific human IgG mAbs such as BAB1, which
      presents high blocking activity in both immunochemical and cellular IgE
      competition experiments, might have therapeutical application.

PMID- 8752952
TI  - Advice for organized medicine.

PMID- 8752953
TI  - Medical savings accounts.

PMID- 8752954
TI  - Walter Reed.

PMID- 8752955
TI  - Telemedicine. Gift from the gods or pandora's box?

PMID- 8752956
TI  - Telemedicine in use. The Medical College of Virginia, The Powhatan Correctional
      Center and the Blackstone Family Practice Center.

PMID- 8752957
TI  - The role of telemedicine in triage decisions for pediatric emergency patients.

PMID- 8752958
TI  - Library outreach across the commonwealth. Pathways to improved health.

PMID- 8752959
TI  - Increasing access to medical information. Changing communication patterns in
      southside Virginia.

PMID- 8752960
TI  - University of Virginia Telemedicine Program. Improving Access.

PMID- 8752962
TI  - Computers in medicine.

PMID- 8752961
TI  - Telemedicine: a physician extender in the delivery of primary pediatric care.

PMID- 8752963
TI  - Telemedicine and the law.

PMID- 8752964
TI  - Lead screening in the general pediatric clinic.
AB  - The overall prevalence of an elevated lead level in the UVa pediatric clinic
      population (5.7%, > or = 10 micrograms/dL; 1.1%, > or = 15 micrograms/dL) was
      lower than that reported by Bronson and Renier (Duluth, Minnesota) (8.2%, > or =
      10 micrograms/dL, and 2.6%, > or = 15 micrograms/dL), Pirkle and colleagues
      (National Health and Nutrition Examination Survey III (9.0%, > or = 10
      micrograms/dL) and Norman and associates (North Carolina) (20.2%, > or = 10
      micrograms/dL; 3.2%, > or = 15 micrograms/dL; 1.1%, > or = 20 micrograms/dL). The
      results are similar to those reported by the city of Denver (3% and 1%,
      respectively). None of the children had a level > or = 25 micrograms/dL, a level
      found in 2.1/1000 children in Massachusetts, or a level > or = 45 micrograms/dL,
      the level recommended for chelation therapy in asymptomatic children. In view of
      the base cost of universal lead screening ($33/test) in the UVa laboratories and
      the lack of an increased prevalence of lead poisoning in the children in the UVa
      clinic, clinic personnel favor screening only those children who have a positive
      response to any of the risk assessment questions, but in particular, the question
      "does your child live in or visit frequently a house built before 1960?"

PMID- 8752966
TI  - [Serum and urinary pyridinium cross-links in patients with predialysis chronic
      renal failure].
AB  - The concentrations of pyridinoline (Pyr), a novel marker of bone resorption, were
      simultaneously measured in both serum and urine samples by ion-paired high
      performance liquid chromatography in 27 patients with predialysis chronic renal
      failure. The patients consisted of 19 males and 8 females, whose creatinine
      clearance (Ccr) ranged from 2.5 to 47.6 ml/min. The influence of residual renal
      function on serum Pyr and the clinical significance of serum and urinary Pyr were
      analyzed in patients with predialysis chronic renal failure. There were
      significant correlations between serum Pyr and serum Cr (r = 0.76) and between
      Pyr clearance and Ccr (r = 0.70). In addition, significant correlations were
      observed serum and urinary Pyr (r = 0.64) and between both serum and urinary Pyr
      and HS-PTH (r = 0.96 and r = 0.61, respectively) and osteocalcin (r = 0.80 and r
      = 0.73, respectively). However, serum bone alkaline phosphatase isoenzyme (ALP3)
      was correlated with neither serum nor urinary Pyr. There was no correlation
      between the ratio of serum Pyr/serum Cr and the metabolic bone markers (HS-PTH,
      osteocalcin and ALP3). There was a correlation between Ccr and urinary Pyr,
      although it was statistically significant (p < 0.1). These date led to the
      following conclusions: (1) serum Pyr in patients with oredialysis chronic renal
      failure is influenced by reduced renal function and (2) urinary pyr shows a state
      of bone resorption when an adegvafe level of renal function is maintained. This
      suggests that patients with an advanced stage of renal osteodystrophy are
      included among cases of predialysis chronic renal failure.

PMID- 8752965
TI  - [Analysis of intraglomerular and interstitial infiltration of leukocytes in
      membranous nephropathy with focal segmental glomerulosclerosis].
AB  - We investigated infiltrating cells in the glomeruli and interstitium in biopsy
      specimens from 41 cases with membranous nephropathy (MN) and found that 21 had
      focal segmental glomerulosclerosis (FGS) and 20 did not. There was no significant
      difference between groups MN +FGS and MN regarding age, interval from onset,
      serum creatinine level and urine protein excretion when the biopsy was performed.
      The cells were analyzed with 3-layer indirect immunoperoxidase techniques using
      monoclonal antibodies to leukocyte common antigen, T cells, B cells and
      monocytes/macrophages (Mo/M phi). The numbers of leukocytes in both glomeruli and
      interstitium increased significantly in group MN+FGS as compared to those in
      group MN, respectively. Most of the leukocytes infiltrating the glomeruli were
      Mo/M phi, while T cells and Mo/M phi were predominant in the interstitium. There
      was a significant correlation between the numbers of intraglomerular and
      interstitial Mo/M phi in group MN+FGS, but not in group MN. Follow-up periods
      after the biopsy were not significantly different between the groups. At the
      final points of follow-up, urine protein excretion significantly decreased in
      group MN, but not in group MN+FGS. In group MN+FGS, serum creatinine levels were
      twice the level found at the biopsy in 5 cases, and 2 required hemodialysis
      therapy. Renal functions were not deteriorated in any cases of group MN. These
      findings suggest that FGS may be one the deleterious factors in MN, which may
      facilitate the infiltration of Mo/M phi in both glomeruli and interstitium and T
      cells in the interstitium.

PMID- 8752967
TI  - [Computed tomographical evaluation of diabetic nephropathy].
AB  - Diabetic nephropathy can be regarded mainly as a type of microangiopathy, but is
      a disease that may also include aspects of macroangiopathy. This is especially
      true of renal disease in non-insulin dependent diabetes mellitus (NIDDM), which
      is characterized not only by diabetic glomerulosclerosis, but also by
      atherosclerosis. We performed morphological studies on the kidney, using computed
      tomography (CT), focusing on such points as: (1) abdominal aortic calcifications
      at the level of kidney, (2) calcifications in the renal artery, and (3) wedge
      shaped defects on the renal surface. We noted that these findings became more
      prominent in NIDDM patients during end-stage renal failure than during normal
      renal function, and were significantly more common in those two NIDDM groups than
      in age-matched nondiabetic patients without hypertension, hyperlipidemia or gout.
      NIDDM patients exhibited these features more frequently than IDDM patients.

PMID- 8752968
TI  - [Clinicopathological study of Henoch-Schonlein purpura nephritis with special
      reference to C3c deposits].
AB  - The aim of this study was to evaluate glomerular C3c deposits of Henoch-Schonlein
      purpura nephritis (HSPN) in children. Fifty-one patients aged 7-15 years (20
      males and 31 females) were studied. On histological investigation, crescent
      formation seen under light microscopy and subepithelial electron dense deposits
      (EDD) under electron microscopy were found to be related to the degree of
      proteinuria and the duration of proteinuria and/or hematuria. A comparative
      clinicopathological study was performed on C3c-positive patients (n = 22) and C3c
      negative patients (n = 25). Histological findings, such as crescent formation and
      subepithelial EDD, had no relation to glomerular C3c-deposits. At renal biopsy,
      C3c deposits were positive in 65 % of patients with heavy proteinuria ( >
      100mg/kg/day), and in 30% of mild proteinuria patients ( < 50mg/kg/day). The
      difference between the two groups was statistically significant (p < 0.05). The
      duration of proteinuria and/or hematuria in C3c-positive patients had a tendency
      to persist in comparison with that in C3c-negative cases. Renal biopsies on many
      cases of C3c-negarive patients were performed following the lapse of three
      months, while the biopsies on patients showing global (+) C3c deposits (n = 15)
      were conducted within the three-month period. These results suggest that
      glomerular C3c deposits influence the clinical conditions of patients with HSPN,
      and complement activation is generated in the early stage of HSPN.

PMID- 8752969
TI  - [Extracorporeal shock wave lithotripsy in an 8-month-old infant].
AB  - An 8-month-old boy who presented with pyrexia and vomiting was referred to the
      pediatric clinic of Kitasato University Hospital. He was found to have hematuria,
      proteinuria and pyuria. Abdominal X-ray film showed calcification suggesting
      renal staghorn calculus in the bilateral kidneys. At 10-months and 11-months, we
      succeeded in treating him with extracorporeal shock wave lithotripsy (ESWL)
      without complications.

PMID- 8752970
TI  - [Long-term effect of transcatheter arterial embolization therapy for renal
      angiomyolipoma].
AB  - We report a case of a 21-year-old man with a right renal angiomyolipoma who has
      been observed for 20 months after successful treatment with selective
      transcatheter arterial embolization (TAE). In May 1993, he was transferred to our
      hospital for the treatment of an abdominal mass. Examination revealed a solid and
      fat-containing right renal tumor on computed tomography (CT) and magnetic
      resonance imaging (MRI), hypervascular staining with multiple peripheral
      microaneurysms on renal angiogram, indicating an angiomyolipoma (AML). He did not
      have any signs of tuberous sclerosis. Because he complained of abdominal pain and
      the tumor was 9 cm in diameter, TAE of the tumor using polyvinyl alcohol foam was
      performed to prevent life-threatening hemorrhage. Renal angiogram after TAE
      demonstrated a complete shut-down of blood supply to the tumor and CT scan, 6 and
      20 months after TAE, demonstrated a decrease in size to 4.5 cm in diameter,
      showing a favorable long-term effect of treatment. He has been symptom-free for
      20 months. TAE appears to be a safe and effective treatment for AML, preventing
      tumor growth and thus possibly hemorrhage or rupture of the tumor over the long 
      term.

PMID- 8752972
TI  - [Basic study of videomicroscopy].

PMID- 8752971
TI  - [Two cases of autosomal dominant polycystic kidney disease treated with
      hemodialysis associated with polycystic liver complications related to the cause
      of death].
AB  - As long-term survival has become possible in patients with autosomal dominant
      polycystic kidney disease (ADPKD) with progress in hemodialysis (HD),
      complications by various extrarenal diseases has presented new problems. Recent
      experience of two rare cases of ADPKD ending fatally due to complications by
      polycystic liver is presented. Case 1: A 60-year-old female with a family history
      of ADPKD without a past history of liver disease, was diagnosed as ADPKD at the
      age of 45 years. Hemodialysis was started at the age of 58 years. From 6 months
      prior to her death, abdominal circumference increased (body height: 149 cm,
      abdominal circumference: 100 cm). Dyspnea, abdominal pain and anorexia appeared
      and she died of hepatic failure leading to cachexia. Case 2: A 76-year-old female
      with a family history of ADPKD without a past history of liver disease, was
      started on HD at the age of 73 years. Abdominal circumference was 84 cm (body
      height: 138 cm). She was repeatedly admitted to and discharged from the hospital
      due to febrile episodes. Infection of polycystic liver was complicated by DIC and
      she died of gastrointestinal hemorrhage. Autopsy revealed abscess in some of the
      cysts in the liver. Hepatic cysts most frequently complicating ADPKD so far have
      presented with scarcely any clinical problems. Recently, however, cases of
      infection of hepatic cysts, portal hypertension and hepatic insufficiency have
      been reported. The relationship between these hepatic diseases and the prognosis
      of ADPKD has received attention. Increase in the number of cases of complications
      similar to the present cases is anticipated.

PMID- 8752973
TI  - [Gene therapy--present states and future perspectives].

PMID- 8752974
TI  - [Replication of human immunodeficiency virus in the cells].

PMID- 8752975
TI  - [Applications of FISH method for diagnosis and pathophysiologic analysis in
      hematopoietic neoplasias].

PMID- 8752976
TI  - [Bone marrow failure--current progress in pathophysiology].

PMID- 8752977
TI  - [Abnormalities in blood cell production].

PMID- 8752978
TI  - [Thrombopoietin].

PMID- 8752979
TI  - [Posttransfusion GVHD].

PMID- 8752980
TI  - [Chemotherapeutic approaches against drug resistant tumors].

PMID- 8752981
TI  - [Disorders of neutrophil function].

PMID- 8752982
TI  - [The selectins, selectin ligands and hemopoitic system].

PMID- 8752983
TI  - [Homozygous beta(+)-thalassemia due to -31 A to G mutation].
AB  - A 20-year-old Japanese woman was admitted to our hospital with anemia and mild
      splenomegaly. Peripheral blood examination revealed Hb 9.4 g/dl, Ht 29.3%, RBC
      4.74 x 10(6)/microliters, reticulocytes 2.4%, WBC 5,200/microliters, platelets
      24.9 x 10(4)/microliters, MCV 61.7 fl, and MCH 19.9 pg. Poikilocytosis with
      target cells was recognized on the peripheral blood smear. A bone marrow aspirate
      revealed erythroid hyperplasia. Serum iron and ferritin were in the normal range.
      beta-thalassemia was suggested by the increase in HbA2 (6.5%) and HbF (7.5%).
      Analysis of beta globin DNA by single strand conformation polymorphism (SSCP) and
      amplification refractory mutation system (ARMS) confirmed a diagnosis of
      homozygous beta(+)-thalassemia due to -31 A to G mutation. A familial study
      revealed that her parents were heterozygous for this allele. This is the 8th case
      of homozygous beta(+)-thalassemia due to -31 A to G mutation in Japan.

PMID- 8752984
TI  - [Influenza-virus associated hemophagocytic syndrome in a patient with pernicious
      anemia].
AB  - A 59-year-old man with pernicious anemia (vitamin B12 deficiency) was admitted
      because of rapidly developing pancytopenia with the symptoms of influenza.
      Laboratory data indicated that the pancytopenia was manifested by influenza virus
      associated hemophagocytic syndrome. In the patients with pernicious anemia, it is
      known that there are immunologic disturbances in either humoral and cellular
      immunity and increased hematopoiesis due to ineffective hematopoiesis. This
      patient was thought to have developed influenza virus-associated hemophagocytic
      syndrome due to the immunologic and hematopoietic abnormality in the pernicious
      anemia.

PMID- 8752985
TI  - [Paternity probability in the cases of incest].
AB  - To calculate the paternity probability in the cases of incest where the alleged
      father was either the father or the brother of the plaintiff's mother, some
      algebraic expressions applicable to a simple codominant diallelic genetic marker
      system were derived by modifying the formulas of Essen-Moller and Komatsu (the
      both formulas gave the same result). The paternity probability in the incest case
      is generally lower than that in usual case, because in the former case an allele
      present in the mother is sometimes found in both the alleged father and the child
      (plaintiff), even if the alleged father is not true father. The paternity
      probability in the incest case, however, becomes higher than that in usual case
      when an allele is common to both the alleged father and the child but not to the
      mother. The mean value of paternity probability becomes lower, as the
      relationship becomes closer between the alleged father and the mother.

PMID- 8752986
TI  - Effects of postnatal cocaine on differentiation of the rat corpus callosum.
AB  - We investigated the effects of cocaine on the development of the corpus callosum.
      Pregnant Wistar strain rats (Thirteenth day of gestation) were used in this
      study. On the day following birth, litters were culled to 8 pups (4 males and 4
      females), and rats were assigned to either a control or drug treatment group.
      From postnatal day 1 (P1, at birth = P0) to P5, cocaine (50 mg/kg) was
      subcutaneously injected to the cocaine-treated pups, and saline in the same
      volume to the control pups. Animals were sacrificed in 110 days and a mid
      sagittal section of the callosum was obtained. From this section the morphometric
      measurement of the corpus callosum was performed. In the control group the rat
      corpus callosum has a sex difference with the male corpus callosum being larger
      than the female's. But this sex difference disappeared in the cocaine group. This
      was attributed to the fact that cocaine-treated male rats indicated a significant
      reduction of callosal area. These findings suggest that the early postnatal
      cocaine can abolish the sexual differentiation of the corpus callosum.

PMID- 8752987
TI  - Frequency of the three STR loci (TPOX, CSF1PO, THo1), in a Japanese population
      determined using a Gene Print STR multiplex kit.
AB  - Allele and genotype frequencies for three tetrametric short tandem repeat loci
      (TPOX, CSF1PO and TH01) were determined in a Japanese population sample (n = 105)
      by means of the Gene Print STR Multiplex system PCR kit, electrophoresis of the
      PCR products in denaturing gels and detection of allelic fragments by silver
      staining. Six alleles each were found for the TPOX, CSF1PO, and TH01 loci and at
      the TPOX locus, we identified an additional mutation allele, which consisted of 7
      AATG repeats. The TPOX, CSF1PO and TH01 loci were apparently 64, 73, and 74%
      heterozygous, respectively. All loci met the Hardy-Weinberg criteria using
      categorized alleles.

PMID- 8752988
TI  - [Methamphetamine-like substance detected only in stomach contents from autopsied
      cadavers].
AB  - In this paper we show that a methamphetamine-like substance was detected in the
      stomach contents of deceased patients who had never taken methamphetamine (MA).
      MA was assayed by using gas chromatography/mass spectrometry. Blood, urine and
      stomach content samples were collected from 65 patients not suspected of taking
      MA. In seven victims, MA-like substance was detected in the stomach contents.
      Concentration of MA-like substance ranged from 0.03 to 0.38 microgram/ml. Though
      MA and amphetamine, a metabolite of MA, were detected in forensic samples of
      patients who had used MA, amphetamine could not be identified in the stomach
      contents of these seven cases. There was no correlation between MA concentration
      and interval of time from death to autopsy. The mechanism of the production of MA
      like substance is not clear. This phenomenon should be paid attention to in the
      course of forensic drug analysis because of the possibility of misjudgement.

PMID- 8752989
TI  - Long-distance PCR of VNTR at the D17S74 (CMM86) locus.
AB  - We have successfully amplified D17S74 (CMM86) alleles by a long-distance
      polymerase chain reaction (PCR) using TaKaRa Ex Taq (a Taq DNA polymerase with a
      3'-exonuclease activity) and Perfect Match Polymerase Enhancer (a special
      polymerase enhancer). We adopted a hot-start technique with TaqStart antibody.
      Because of the high guanine content (60%) in D17S74 alleles, removal of K+ from
      the buffers was quite effective. The use of K(+)-free buffers reduces premature
      chain termination in G-rich regions, thereby facilitating amplification of
      targets containing such sequences. The 17 alleles amplified from DNA samples of
      72 unrelated Japanese subjects ranged from 1.05 to 3.5 kb, with a heterozygosity
      of 92%. PCR amplification of D17S74 alleles makes their detection simpler than by
      conventional Southern blotting, and increases the practical utility of the locus.

PMID- 8752990
TI  - [A case of death due to mitral regurgitation caused by traumatic mitral valve
      injury].
AB  - A 51-year-old male, who had been driving a motor bicycle, was involved in a
      traffic accident with a trailer, and he died immediately after the accident.
      According to the external examination of the victim, no fatal injuries were
      found. The medico-legal autopsy revealed a rupture of the left side of the
      pericardium, and a tear of the posterior leaflet of the mitral valve. There were
      no injuries of the papillary muscles and chordae. The cause of death was due to
      traumatic mitral regurgitation.

PMID- 8752991
TI  - [A method to calculate the probability of paternity between relatives--a
      paternity case where the putative father was a deceased granduncle].
AB  - To test paternity in a case where the putative father was a deceased uncle of
      mother (plaintiff's granduncle), we designed a new method to calculate the
      probability of paternity likelihood. The putative father's genotypes of red cell
      antigens, HLA and short tandem repeat (STR) polymorphism were estimated from
      those of mother and sister of the plaintiff. When the probability was calculated
      from the frequencies in the unrelated individuals (the standard method), a
      significant bias might be introduced since the putative father and the plaintiff
      were likely to have the same alleles come from their common ancestry. Therefore,
      we designed a new method to calculate the likelihood ratio from the frequencies
      in the group of mother's uncles estimated from mother's genotypes. The
      probability (0.9299) calculated with our method was found to be lower than that
      (0.9992) done with the standard method indicating that the new method could
      remove the bias introduced from the incest.

PMID- 8752992
TI  - [Shotshell injuries--single or multiple shots?--a case report].
AB  - The case of a 64-year-old hunter who was accidentally shot at a distance of 40
      meters with a shotgun by a member of hunting group was reported. At the scene,
      the victim was found dead and showed two bullet wounds in the left lateral chest
      and thigh, and a penetrated wound in the left knee. Autopsy findings revealed
      that the former two wounds were discharged from the left side of the body, and
      the last one in the knee from the right. The assailant and comrades who happened
      to be on the scene of the accident deposed that the only one shot sound was heard
      at that time. Whether quite different directions of these three wound tracks
      could be explained with single shot or multiple ones, we discussed the locus of
      the bullets in consideration of the posture of the victim.

PMID- 8752993
TI  - Screening of antipsychotic drugs by wide-bore capillary gas chromatography with
      nitrogen phosphorus detection--detection levels in plasma.
AB  - The detection levels of 12 antipsychotic drugs as ascertained from drug screening
      were examined in order to use the screening results effectively for treatment of
      patients or medico-legal examinations in cases of poisoning. Wide-bore capillary
      gas chromatography with nitrogen phosphorus detection was used for the analysis.
      The detection limits of drugs in plasma using 3 extraction procedures, single
      solvent, 3-step solvent and solid-phase extractions were 50-100 ng/ml, 10-200
      ng/ml and 5-50 ng/ml, respectively. The detection limits were compared with blood
      levels previously reported in the literature. Only 4 drugs were detected at the
      therapeutic level, thioridazine, floropipamide, sultopride and oxypertine using
      the single-solvent extraction procedure. Using the 3-step solvent extraction
      procedure, chlorpromazine, levomepromazine and zotepine in addition to the above
      4 drugs were detected. Using the solid-phase extraction procedure, 8 of 12 drugs
      were able to be detected at the therapeutic level, with the exception of
      perphenazine, haloperidol, bromperidol and nemonapride. These data were proved to
      be useful for a rapid forensic diagnosis.

PMID- 8752994
TI  - [3D-CT of the central nervous system].

PMID- 8752995
TI  - [Pathophysiology of hypoxia-ischemia in the developing brain].

PMID- 8752996
TI  - [MRI abnormalities of the brain in neurologic complications following treatment
      of cancer in children].
AB  - During a 3-year period, 6 of 50 children with systemic malignacies developed
      neurologic complications such as hemiparesis, convulsions and loss of
      consciousness. The children consisted of 1 boy and 5 girls, from 3 to 12 years
      old, 3 with acute lymphoblastic leukemia and 3 with malignant lymphoma. Four
      patients received induction treatment that included intravenous administration of
      L-asparaginase and/or intrathecal administration of methotrexate. One patient
      received induction treatment and consolidation treatment that included
      intravenous administration of L-asparaginase. One patient received induction and
      consolidation treatment, and the protocol for peripheral blood stem cell
      transplantation. Laboratory examinations revealed coagulation dysfunction in 3
      patients treated with L-asparaginase and 1 patient with disseminated
      intravascular coagulation (DIC). Magnetic resonance imaging (MRI) was performed
      on a 1.5-T unit, using spin-echo or fast spin-echo sequences. T1-weighted, T2
      weighted, and proton density-weighted images were obtained in the axial and/or
      coronal plane (section thickness, 4 mm; inter-section gap, 2 mm). MRI was
      initially performed within 36 hours after the onset in all patients, and follow
      up MRIs were performed for 6 months. MRI showed lesions involving the cortex and
      subcortex in 4 patients with coagulation dysfunction. In 2 of these 4 patients,
      Gd-enhanced T1-weighted images showed contrast enhancement in the surface of the
      gyrus, suggesting focal vascular stasis. Serial MRI revealed nearly complete
      resolution of the lesions. Symptoms were relieved in every case. The lesions on
      MRI were presumed to be due to venous thrombosis related to the coagulation
      dysfunction caused by L-asparaginase or DIC. On the other hand, in 2 patients
      with onset after intrathecal administration of high-dose methotrexate and
      cytarabine, MRI revealed multiple lesions involving the centrum semiovale and
      periventricular white matter. No Gd-enhancement of the lesion was detected. This
      MRI finding was consistent with leukoencephalopathy. As time passed, the symptoms
      improved completely, and the lesions became better demarcated. MRI is useful for
      differentiating lesions related to coagulation dysfunction from
      leukoencephalopathy.

PMID- 8752997
TI  - [Usefulness of reaction times in high-cortical recognition tasks].
AB  - We compared reaction times for high-cortical recognition tasks with kana
      searching test in a group of 46 normal individuals aged 21 to 83 who gain a full
      score in Mini-Mental State. The following tasks of reaction time were used;
      simple reaction time (SRT), choice reaction time (CRT), memory scanning time
      (MST), and visual searching time (VST). The results were consistent and
      demonstrated that mean reaction time of 46 individuals increased in difficult
      tasks such as MST or VST. All reaction times increased depending on aging, which
      became longer in difficult tasks. Score of kana-searching test was correlated
      with MST and VST, but did not correlate with SRT and CRT. These findings suggest
      that reaction times may be useful for mass-screening of high-cortical functions
      in different ages as well as the kana-searching test.

PMID- 8752998
TI  - [Needle electromyography in the thoracic paraspinal muscles of motor neuron
      disease].
AB  - Usefulness of needle electromyography (EMG) in the thoracic paraspinal muscles
      was investigated in 22 patients with amyotrophic lateral sclerosis (ALS). All
      patients revealed denervation changes in the thoracic paraspinal muscles, though
      the EMG findings were insufficient to fulfill the WFN criteria of lower motor
      neuron sign. We could not diagnose three patients as having ALS at their first
      visits by conventional EMG. One patient had restricted neurogenic change within
      one limb and two patients had cervical spondylosis causing difficulty to diagnose
      anterior horn cell involvement at the cervical level. In these patients, however,
      we believed to having ALS because of the neurogenic findings of EMG in the
      thoracic paraspinal muscles. Afterwards, they became clinically definite ALS. On
      relation to respiratory function, patients with acute denervation potentials
      (fibrillation potentials) in upper thoracic paraspinal muscles innervated by Th1
      approximately Th4 had respiratory dysfunction (% VC is less than 80). Two
      patients had the acute denervation potentials in the upper thoracic paraspinal
      muscles before the decrease in % VC. We conclude that needle EMG testing in
      thoracic paraspinal muscle is useful to diagnose ALS in early stage and to
      predict respiratory failure in ALS patients.

PMID- 8753000
TI  - [Analysis of proximal conduction time of the median nerve in patients with
      diabetes mellitus].
AB  - Proximal conduction time (PCT) of the median nerve was calculated from the data
      obtained by conventional motor conduction studies in 272 diabetics and in 35 age
      matched healthy controls. M-latency and F-latency obtained by stimulation at the
      wrist (Mw and Fw, respectively) and M-latency at the Erb's point (Me) were used
      to calculate PCT (Fw + Mw - 2Me), which represents turnaround time between Erb's
      point and anterior horn cell. Each indices were corrected using the standard
      patient's height of 160cm. Severity of diabetic neuropathy was shown by the
      polyneuropathy index (PNI), which was calculated from 12 indices derived from the
      motor nerve conduction studies on 4 nerves of the right arm and leg. Significant
      differences were found in Mw, Fw and Me between diabetics and controls (p <
      0.01), although the results of PCT were similar between them. In diabetics Mw (r
      = -0.55), Fw (r = -0.56) and Me (r = -0.60) had a significant negative
      correlation with PNI, but the correlation between PCT and PNI was relatively low
      (r = -0.22). Using the proximal conduction time calculated readily from
      conventional motor nerve conduction studies, delay in the proximal conduction was
      shown to be smaller than that in the distal conduction in diabetic
      polyneuropathy.

PMID- 8752999
TI  - [TCR alpha beta + CD4- CD8- T cells among the peripheral blood mononuclear cells
      of myasthenia gravis patients].
AB  - We investigated the occurrence of TCR alpha beta + CD4- CD8- mononuclear cells
      (DN alpha beta T cells) and TCR gamma delta + CD3+ mononuclear cells (gamma delta
      T cells) among the peripheral blood mononuclear cells of 22 myasthenia gravis
      patients (MG) and 22 controls in order to examine whether extrathymic T cell
      subpopulations might be responsible for the pathogenesis of MG. The differences
      between the mean percentages of both DN alpha beta T cells and gamma delta T
      cells in the MG patients (DN alpha beta T cells: 0.53 +/- 0.51%, gamma delta T
      cells: 3.45 +/- 2.79%) and the controls (DN alpha beta T cells: 0.32 +/- 0.16%,
      gamma delta T cells: 3.81 +/- 2.36%) were not significantly different. However,
      higher DN alpha beta T cells ratios (1.48 approximately 1.84%) were noted in
      three MG patients. Thymectomy and subsequent thorough dissection of the anterior
      mediastinum 3 years after thymectomy had no effect on the symptoms of one
      patient, a 25-year-old woman without thymoma. The other two patients, a 45-year
      old man and a 41-year-old woman without thymoma, had recurrences despite long
      term remissions (14 years and 30 years, respectively) after thymectomy.
      Examination of DN alpha beta T cells, which are probably generated
      extrathymically without negative selection, may play an important role in
      understanding the pathogenesis in these three cases of MG.

PMID- 8753001
TI  - [Usefulness and problems of high dose chemotherapy using CBDCA, VP-16, and MCNU
      with peripheral blood stem cell transplantation in pediatric malignant brain
      tumors].
AB  - The aim of this study was to evaluate efficacy of high dose chemotherapy and
      restoration of hamatopoiesis following peripheral blood stem cell transplantation
      (PBSCT). Three patients with pediatric malignant brain tumors (two
      medulloblastomas and one medullomyoblastoma) underwent high dose chemotherapy
      including CBDCA, VP-16, and MCNU with PBSCT. Postcontrast-MR images revealed no
      abnormal enhancing lesions after high dose chemotherapy in all patients. One
      patient with medulloblastoma has remained complete remission one year and seven
      months after the termination of treatment. Another patient with
      medullomyoblastoma died of respiratory distress syndrome one month after the
      second course of high dose chemotherapy. The other patient with medulloblastoma,
      which received PBSCT and high dose chemotherapy at the time of tumor recurrence
      after failure of initial treatment, suffered from multiple disseminated lesions
      five months after the treatment. PBSCT contributed prompt recovery from
      hematopoietic dysfunction in all patients. These results indicate that PBSCT may
      play an important adjuvant to chemotherapy and further offer a safer and more
      effective high dose chemotherapy in pediatric malignant brain tumor patients.

PMID- 8753002
TI  - [Diffusion/perfusion MRI study on cerebral ischemia in a rat embolism model].
AB  - To determine whether intracerebral distribution of clot emboli can induce
      perfusion deficits and ischemic brain injury in a rat embolism model,
      diffusion/perfusion magnetic resonance imaging techniques were employed using a
      4.7 Tesla imager. Clot emboli produced from venous blood were injected into the
      right internal carotid artery of male Sprague-Dawley rats. Diffusion-weighted
      spin-echo imaging was used to detect early ischemic injuries due to cytotoxic
      edema every 30 minutes. Sequential echo-planar imaging (EPI), as a form of
      perfusion imaging, was carried out following bolus i.v. injection of the magnetic
      susceptibility contrast agent Dy DTPA-BMA. Images (EPI) were also made during
      clot embolization to localize the distribution of the emboli. The images obtained
      showed signal loss in the right hemisphere corresponding to the distribution of
      the emboli result of the magnetic susceptibility effect of deoxyhemoglobin. The
      spatial distribution of the signal loss corresponded to the perfusion deficits,
      decreased ADC (apparent diffusion coefficient) areas on diffusion images, and
      histological abnormalities on TTC-stained specimens. After intra-arterial
      streptokinase infusion following clot embolization, decreased perfusion deficits
      and abnormal ADC areas were monitored by diffusion/perfusion MRI.
      Diffusion/perfusion MR imaging thus provided excellent in vivo mapping of the
      distribution of the emboli in relation to cerebral perfusion deficits and acute
      ischemic injury in the rat embolism model.

PMID- 8753003
TI  - [MRI findings of hyperostosis frontalis interna--a case of Morgagni syndrome].
AB  - We report a patient with Morgagni syndrome. The main aim of this paper is to
      discuss hyperostosis frontalis interna (HFI) and coexisting clinical feature and
      to describe the pathomorphology in detail on the basis of MRI images of the
      skull. The patient, a woman, was 82 years old when she first came to our
      hospital. She had a 20-year history of hypertension and chronic headache, and had
      been excessively obese till three years before. On admission she presented with a
      broad spectrum of clinical symptoms and signs including insomnia, disorientation
      to place, loss of memory, dementia, night delirium, reduced deep tendon reflexes
      in the lower extremities, urinary incontinence and upward gaze palsy. Because of
      a fair recovery within several days, it was suspected that so-called "treatable
      dementia" played a considerable role in the above-mentioned clinical state.
      Laboratory testing data, including hormone levels, were all within normal limits.
      EEG examinations showed slowed, diffuse, and poorly developed alpha-waves with no
      paroxysms. Cranial CT in horizontal sections disclosed a deformed frontal bone
      with convexlens-shaped thickening bilaterally and diffuse high density on both
      sides. MRI images revealed more detailed structures: the outer plate, diploe and
      inner plate of the skull, and abnormal ossifications. Based on these findings we
      diagnosed her illness as Morgagni syndrome. Recent reports, though few in number,
      have tended to focus on the EEG findings, hormones and psychiatric states in this
      syndrome, and descriptions of the HFI itself seem to be rare. The true cause of
      this syndrome is not yet known, so this rare presentation of MRI images of HFI is
      thought to be important in explaining this peculiar phenomenon in the skull.

PMID- 8753005
TI  - [A 34-year-old woman with delayed motor milestones, high arched palate, and
      proximal muscle weakness].
AB  - We report a right-handed 34-year-old woman with diffuse muscle atrophy. The
      patient was a full-term infant of uneventful delivery, however, motor milestones
      were delayed in that neck control was obtained at 10 months of the age and she
      started to walk unassisted at 2 years of the age. Mental development was normal.
      She was unable to run with her mates at her kindergarten and she required a
      handrail when she walk up the stairs. She could not close her mouth completely at
      the primary school. She was unable to use a straw as a middle school pupil.
      Recently, she noted difficulty in raising her head from the supine position, and
      has become unable to walk a long distance. She was admitted to our hospital in
      September 17, 1994 when she was 34-year-old. On admission, general physical
      examination revealed that she looked slender weighing 38 kg with 149.5 cm height.
      She showed a high arched palate, slight scoliosis, and pes equinus. Otherwise
      general physical examination was unremarkable. Upon neurologic examination, she
      was alert and well oriented. Cranial nerves were unremarkable except for
      bilateral facial atrophy and moderate weakness. Her voice was of nasal quality,
      and swallowing was slightly difficult. No atrophy was noted in the
      sternocleidomastoid muscle. She showed waddling gait and positive Gowers' sign.
      Diffuse muscle atrophy was noted and mild to moderate weakness was presented more
      in the proximal part in both upper and lower extremities, however, deltoid
      muscles retained normal power. No ataxia was noted. All the deep tendon reflexes
      were lost. Sensation was intact. Routine laboratory examination was unremarkable.
      Serum CK was 56 IU/l. Electromyography revealed myogenic changes in the deltoid,
      biceps, and quadriceps muscles. A diagnostic biopsy was performed in the left
      biceps brachii muscle. The patient was discussed in the neurologic CPC, and the
      chief discussant arrived at the conclusion that the patient had nemaline
      myopathy. Opinions were divided among nemaline myopathy, central core disease,
      and congenital fiber type disproportion. Histologic examination of the biopsied
      specimen revealed marked atrophy of type 1 muscle fibers; many central nuclei
      were seen in the type 1 fibers. Approximately 70% of the muscle fibers were type
      1 fibers. No nemaline rods or central cores were noted. Histologic appearance was
      consistent with the diagnosis of congenital fiber type disproportion.

PMID- 8753004
TI  - [A case of progressive hemifacial and hemispheric atrophy with multiple hemi
      intracerebral calcifications presenting with occipital lobe epilepsy].
AB  - A 30-year-old man with progressive hemifacial atrophy is described. He had right
      hemifacial atrophy and epileptic seizures first noted at the age of about 15
      years. Examination revealed atrophy of the right half of the tongue, skin
      pigmentation in the right neck, grizzled hair on the right side of the head, and
      left upper temporal homonymous hemianopsia. CT and MRI revealed multiple
      intracerebral calcifications, and EEG showed spike discharges predominantly in
      the right occipital lobe, ipsilateral to the hemifacial atrophy. The epileptic
      seizures were associated with visual hallucinations that are characteristic of
      occipital epilepsy. A skin biopsy obtained from the pigmented region in the right
      neck showed chronic inflammatory changes consisting of severe atrophy of the
      epidermis, dermis, and fatty tissue, marked proliferation of collagen fibers, and
      perivascular infiltration by round cells and giant phagocytes. Previous
      descriptions on the pathogenesis of hemiatrophy of the face and brain were
      reviewed in relation to the present case.

PMID- 8753006
TI  - [DNA synthesis in the testes of infertile men with varicocele--image cytometeric
      analysis of proliferating cell nuclear antigen].
AB  - BACKGROUND: The analysis of cell kinetics of germ cells have been implicated as
      important clue to investigate the etiology of infertile patients. We examined the
      germ cell kinetics of varicocele testis using proliferating cell nuclear antigen
      (PCNA) immunostaing by image cytometry (CAS 2000), which is very accurate and
      useful method to evaluate the staining intensity. PATIENTS AND METHODS:
      Testicular biopsy specimen obtained from 28 cases of male infertility with left
      varicocele and 5 normal controls were quantitatively examined concerning PCNA
      expression. Positive rate of PCNA (PR) was expressed as the percent of nuclear
      area positively stained with PCNA monoclonal antibody compared with total nuclear
      area analyzed in more than 20 seminiferous tubules. A hematoxylin and eosin
      stained sections, which were fixed in Bouin's solution were used to examine
      Johnsen's mean score by photomicroscopy. RESULTS: PR of right and left testes of
      varicocele patients were 11.3 +/- 4.8% and 11.3 +/- 4.1%, respectively. PR of
      normal testes was 21.7 +/- 3.1%. PR of each side were reduced similarly and the
      difference of PR between right and left testes of varicocele patients were not
      significant. Bilateral PR was 11.4 +/- 4.1%. Bilateral PR was significant lower
      than that of normal testes (p < 0.001). Concerning varicocele grade, sperm
      concentration of seminogram, Johnsen's mean score and the improvement of
      seminogram, no significant correlations between PR and those were observed.
      CONCLUSION: PR evaluated by image cytometry is very useful biological parameter
      to assess the germ cell kinetics. In varicocele patients, not only left side but
      also right side of testes were deteriorated in the cell kinetics and the decrease
      in DNA synthesis is one of the causes that have deleterious effects on
      spermatogenesis.

PMID- 8753007
TI  - [Clinical evaluation of grade 3 superficial bladder cancer].
AB  - PURPOSE: To evaluate the treatment of grade 3 superficial bladder tumor,
      retrospective analysis of superficial bladder tumors was performed with special
      references to tumor progression and prognostic factors. MATERIALS AND METHODS:
      From 1976 to 1994, 247 cases with pTa-pT1 superficial bladder tumor were treated.
      Mean duration of follow up 77.3 months. These patients were divided into pTa
      (196), pT1 (52), grade 1 (61), grade 2 (196) and grade 3 (62). The prognostic
      factors were calculated with multivariate and univariate analysis. Tumor
      progression was defined as muscle invasion or distant metastasis. RESULTS: G3
      tumor showed poor prognosis and was more frequent in tumor progression compared
      with G1 and G2 tumors (19.4% vs 0% and 1.6%). According to multivariate analysis,
      significant variables for actual survival rate were patient age and tumor grade.
      Tumor grade, recurrence and tumor configuration were also significant risk factor
      for cause-specific survival rate. By univariate analysis, patient age, tumor
      configuration, tumor size, multiplicity and concomitant CIS in G3 group were
      different from the other two G groups. In the G3 group, only recurrence was the
      predictable factor for progression. Analysis of prognosis and therapeutic
      modality revealed that G1 and G2 tumors were sufficiently controlled by
      endoscopic treatment. On the other hand, 21 cases (33.9%) of G3 tumor required
      total cystectomy after all. 11 cases of G3 group died of bladder cancer.
      Lymphatic involvement was detected in some cases of G3 tumor even if superficial.
      This factor showed a little relevance to poor prognosis of G3 tumor. CONCLUSION:
      Tumor grade was thought to be the most important risk factor of superficial
      bladder tumor. These results suggested that total cystectomy should be considered
      for the treatment of superficial G3 bladder cancer when recurrence occurs or
      conservative treatment is though to be failed.

PMID- 8753008
TI  - [Autoradiographic studies of oxalate distribution in rat kidney].
AB  - BACKGROUND: We performed macro and micro-autoradiographic studies using 14C
      oxalate in normal and hyperoxaluric rats in order to elucidate intrarenal
      distribution of oxalate and to determine where calcium oxalate crystal can be
      adhere in the kidney. METHODS: Macro and micro-autoradiographic studies of the
      kidney in normal rats were carried out at intervals of 15, 30 and 90 min after
      intravenous administration of 14C-oxalate (37 MBq/kg BW). Hyperoxaluria was
      induced by vitamin B6 deficient diet. The procedure of macro and micro
      autoradiography is the same as that in normal rat. RESULTS: In normal rats,
      macroautoradiogram showed that the radioactivity of 14C-oxalate exists in the
      whole kidney, and microautoradiogram identified this radioactivity mainly in the
      extraluminal space of renal tubules at 15 min. Macro and micro-autoradiograms
      taken 90 min after the injection showed practically no radioactivity of 14C
      oxalate in the cortex or the medulla, but it was located in the extraluminal
      space of the papilla. In hyperoxaluric rats, macroautoradiogram showed some
      spotty accumulations of 14C-oxalate in the inner medulla and papilla.
      Microautoradiogram revealed that these accumulations are mainly seen in the
      extraluminal space. CONCLUSION: These results indicate that in normal rats the
      injected 14C-oxalate remains in the renal papilla, especially in the extraluminal
      space, when nearly all oxalate was excreted by urine, and in hyperoxaluric rats
      14C-oxalate exists there as calcium oxalate crystal or microlith.

PMID- 8753009
TI  - [Results of antireflux surgery in infants with vesicoureteral reflux].
AB  - BACKGROUND: Due to the advancement of prenatal and postnatal ultrasound screening
      in addition to better understanding by pediatricians, more infants have been
      detected to have vesicoureteal reflux. There are still debates, however, about
      their management whether to take conservative or surgical treatment. METHODS: We
      analysed clinical courses of 51 children with primary reflux undergoing
      antireflux surgery when they were under 1 year. RESULTS: A total of 41 infants
      (80%) presented with febrile urinary tract infections. The first UTI was seen as
      early as 7th day after birth, with the average age of 2 months. Seven infants had
      hydronephrosis detected by prenatal ultrasound, and 2 were identified by neonatal
      screening ultrasonography. Sixty-eight of 86 reflux ureters (79%) showed high
      grade reflux (grade IV approximately V). All the other 18 ureters with mild to
      moderate grade of reflux except one accompanied with contralateral high grade
      reflux. One ureter with grade II reflux was associated with contralateral
      obstructed meganreter. Renal parenchymal abnormalities, either with scarring
      and/or small kidney, were identified in 64 kidneys (74%) at or before the
      reimplantation. The operation was done as early as 1 month-old with the average
      age of 5.6 months. Among the children, 24 (47%) underwent anti-reflux surgery
      before 6 month-old. Smallest infant weighted 2500 gr at the time of operation.
      Reimplantation was done by the Cohen transverse advancement technique in 75
      ureters (87%). The modified Politano-Leadbetter method in 6 with Hutche's
      diverticulum, and the Glenn-anderson advancement method in 5 with moderate to
      mild reflux. Two dilated ureters were treated with folding of the intravesical
      segment. Follow-up voiding cystourethrogram of 49 children at 6 months revealed
      no evidences of persistent reflux. There were no patients with obstruction of
      reimplantation except one with slight upper-tract dilatation. One infant revealed
      new low grade contralateral reflux, and he is being observed. Two children
      presented pyelonephritis after the operation. CONCLUSION: Our success rate of
      100% in antireflux surgery enables us to continue our policy to perform early
      operative interventions in infants with high grade reflux. In addition to the
      meticulous and careful technique, the conditions for successful results include;
      1) A through checkup of the lower tracts by VCG and endoscopy. 2) Find the better
      operative instruments for the small bladder. 3) Do not hesitate to perform the
      ureteral tapering. 4) Make good use of operative loupe.

PMID- 8753010
TI  - [Clinical review of 105 cases of adrenal tumor, with special reference to
      incidental tumor].
AB  - We reviewed 105 patients with adrenal tumor diagnosed at our institute from
      January 1984 to December 1993. In 74 patients tumors were symptomatically
      diagnosed (the symptomatic group), while in the remaining 31 patients tumors were
      incidentally detected (the incidental group). In 5 cases of the incidental group,
      tumors were found at a routine health examination, whereas in the remaining 26
      cases tumors were found during the examination or treatment for unrelated
      diseases. On both the incidental group and symptomatic group, higher right-to
      left side ratio was noted in the laterality of tumors detected by ultrasound
      scanning. The size of tumors in the incidental group was significantly larger
      than that in the symptomatic group, but there was no significant difference in
      size between the tumors detected by ultrasound and those detected by CT scan in
      either the symptomatic group or in the incidental group. In the symptomatic group
      71 patients (95.9%) were found to have functioning tumor, where the most common
      diagnosis was primary aldosteronism (44 cases), and 68 of the 71 patients
      received adrenalectomy. While in the incidental group 12 patients (38.7%) were
      found to have functioning tumor, where the most common diagnosis was
      pheochromocytoma (7 cases), followed by Cushing's syndrome (3 cases) including
      one case with so-called pre-Cushing's syndrome, and all of the 12 patients
      received adrenalectomy. Of 16 primary incidental adrenal tumors which did not
      have any hormonal functions, 5 tumors larger than 30 mm in diameter were resected
      and the remaining 11 tumors were followed up without operation. Since the
      incidence of incidental adrenal tumor may increase in the future, careful
      diagnosis and decision of indication for surgery are required.

PMID- 8753011
TI  - [Intravesical oxybutynin hydrochloride in the treatment of urge incontinence in
      the elderly].
AB  - PURPOSE: This study was carried out to determine the effectiveness of
      intravesical oxybutynin hydrochloride on urinary urge incontinence in elderly
      people. METHODS: The subjects consisted of 13 patients with an average age of 75
      years who demonstrated uninhibited detrusor contraction on cystometrogram. The
      trial protocol consisted of a pretreatment cystometrogram followed by the
      intravesical administration of 10 ml solution containing 5 mg oxybutynin
      hydrochloride (pH 5.85). The urodynamic studies were repeated one hour later.
      RESULTS: The mean bladder capacity before and after one hour of intravesical
      oxybutynin hydrochloride was 161 +/- 62 ml and 196 +/- 71 ml (mean +/- 1 S.D.,
      n.s.). The rate of improvement was 15.4% (2 cases) in all 13 patients. Four
      patients out of 13 patients continued intravesical administration of the solution
      twice daily. Urinary incontinence disappeared in two patients and incontinence
      was markedly decreased in one. In the remaining patient, urinary incontinence did
      not change because of increased residual urine. Three patients have continued
      this therapy over one years and no side effects were observed. In these patients,
      residual urine volume did not increase. CONCLUSION: It is suggested that
      intravesical oxybutynin hydrochloride is an effective option of therapy for
      intractable urge incontinence in elderly people, however, the immediate
      posttreatment cystometrogram was not predictive of the response to intravesical
      therapy on overactive bladder in the elderly.

PMID- 8753012
TI  - [Characterization of tumor infiltrating lymphocytes from patients with renal cell
      carcinoma--influence of combination therapy with interferon alpha and gamma].
AB  - BACKGROUND: In an attempt to define the effects of combination therapy with
      interferon alpha and gamma, lymphocyte subsets in tumor site and peripheral blood
      have been studied. METHODS: Tumor Infiltrating Lymphocytes (TILs) and Peripheral
      Blood Lymphocytes (PBLs) from 13 interferon-treated and 11 untreated patients
      with primary renal cell carcinoma were characterized by two color flowcytometry.
      Interferon-treated patients received interferon alpha and interferon gamma before
      radical nephrectomy; Interferon alpha was administrated intramuscularly at a dose
      of 3 x 10(6) units every other day from a week before nephrectomy. Interferon
      gamma was administrated as intravenous drip infusion at a dose of 10(6) units
      after interferon alpha administration. RESULTS: In both groups, both TILs and
      PBLs comprised about 70% of CD3-positive cells and CD3-positive TILs comprised
      significantly larger number of HLA-DR positive (activated T) cells compared to
      CD3-positive PBLs. Although TILs showed smaller number of CD4-positive cells
      compared to PBLs, TILs comprised more CD4+ Leu8- (helper T) cells than PBLs. Only
      in interferon-treated group, TILs comprised larger number of CD8+ CD11b
      (cytotoxic T) cells than PBLs and CD16-positive cells (natural killer cells) than
      TILs in untreated group. CONCLUSION: These results suggest that antitumor effects
      of interferon alpha and gamma combined administration may be concerned with
      natural killer cells and cytotoxic T cells in tumor site.

PMID- 8753013
TI  - [Flow cytometry analysis of the DNA content of the prostate cancer--study on the
      tumor heterogeneity in prostate cancer].
AB  - PURPOSE: Clinical significance of DNA ploidy pattern and its DNA heterogeneity is
      examined in prostate cancer. METHODS: Fresh needle biopsy specimens were analyzed
      with flow cytometry and were compared with histopathological findings in 42
      patients. RESULTS: Seven patients had stage B (1 case of B1, 6 cases of B2), 14
      had stage C and 21 had stage D disease respectively. Histopathologically, 18 of
      the cases were well, 12 were moderately and 12 were poorly differentiated
      adenocarcinoma. Diploid was observed in 20, aneuploid in 22. Though 22 cases
      showed no DNA heterogeneity, 14 had type A heterogeneity with aneuploid in
      association with diploid pattern, and 6 cases had type B heterogeneity in which
      multiple aneuploid patterns with different D.I. values were observed. The
      heterogeneity was observed in 28% of well, 58% of moderately and 67% of poorly
      differentiated adenocarcinoma, respectively, and also in 14% of stage B, 50% of
      stage C and 57% of stage D patients, respectively. CONCLUSION: We conclude that
      DNA heterogeneity in prostate cancer is more frequently seen in poorer
      differentiated ones on histologic grade and in more advanced ones on clinical
      stage.

PMID- 8753014
TI  - [Bronchial arterial infusion therapy for lung metastases of urogenital tumors].
AB  - Three patients with lung metastases of urogenital tumors were treated by
      bronchial arterial infusion therapy. Case 1: A 52-year-old man who had multiple
      lung metastases of right renal cell carcinoma fell into a dyspnea at 5 months
      after right radical nephrectomy. Though the effects of resection or laser
      coagulation with bronchoscopy were temporary, two sessions of BAI therapy with
      radiation improved the symptom of dyspnea for at least 3 months. Case 2: A 53
      year-old man who had multiple lung metastases of right renal cell carcinoma was
      treated with systemic chemotherapy after right radical nephrectomy. Because the
      systemic chemotherapy showed only minor response, two sessions of BAI therapy
      were performed. No lung metastasis was detected in radiographs for 2 years after
      BAI therapy. Case 3: A 69-year-old man who had multiple lung metastases of left
      ureteral tumor was treated with 3 sessions of systemic chemotherapy. Though the
      systemic chemotherapy was effective, 2 sessions of BAI therapy with radiation
      showed a more suppressive effect, and the regrowth was not detected for 7 months
      after the therapy was performed. We concluded that BAI therapy was an effective
      therapeutic method not only for cases with no operative indication, but also for
      cases in which systemic chemotherapy was not effective.

PMID- 8753015
TI  - [The characteristics of clinical features of pulmonary tuberculosis in female].
AB  - We studied the clinical features of culture-positive, previously untreated
      patients with pulmonary tuberculosis (77 in females and 200 in males), with
      special reference on the gender differences in clinical features. The mean age
      was 50.8 y.o. for female and 54.4 y.o. for male, and the age distribution was
      almost similar to that of newly-registered patients of whole Japan in 1993,
      namely, small peak in 20s decade and large peaks in the age group over 50 in
      female, and gradual increase up to 50 years and get to plateau in male. Thirty
      nine % in female and fifty-four % in male had various past histories and/or
      complications which might affect to the deterioration of tuberculosis, such as
      diabetes mellitus, liver function distress, respiratory failure, malignancy,
      stomach resection and so on. The rates with each complication were, in general,
      higher in male than in female. The positive rate to Mantoux reaction was higher
      in female than in male, and stronger reactions were observed in female than in
      male. According to the classification of pulmonary tuberculosis designed by the
      Japanese Society for Tuberculosis (GAKKAI classification), the site(s) of
      affected lung, the stage and the extent of lesions were more advanced in male
      than in female, and the positive rate and the amount of bacilli on smear were
      higher in male than in female. The most marked difference was the location of the
      main lesions, 80% in the apical and posterior segments of upper lobe (S1,2) and
      8% in the superior segments of lower lobe (S6) in male, while 60% in S1,2 and 25%
      in S6 in female. The rate of complete resistance against to anti-tuberculosis
      agents was higher in male than in female, but the combination chemotherapy of
      isoniasid and refampicin with streptomycin or ethambutol was almost equally
      effective both in males and females, and almost all patients converted to bacilli
      negative within three months after the initiation of the chemotherapy, except in
      a few male patients.

PMID- 8753016
TI  - [Rapid detection of acid-fast bacilli with Mycobacteria Growth Indicator Tube
      (MGIT)].
AB  - The BBL MGIT Mycobacteria Growth Indicator Tube is a novel broth based culture
      system for the detection of mycobacteria from clinical specimens. The tubes
      consist of a fluorescent indicator embedded in silicone on the bottom of a 16x100
      mm round-bottom tube, filled with 4ml of an enriched BBL Middlebrook 7H9 broth
      base, with 0.25% glycerol. Actively growing mycobacteria consume the oxygen
      dissolved in the medium and fluorescence will occur when the tubes are observed
      with a 365nm transilluminator. The purpose of this study is to evaluate
      comparatively MGIT with 1% Ogawa egg medium by using two hundred and forty-five
      clinical specimens. The samples were digested, decontaminated and concentrated
      for culture using N-acetyl-L-cysteine-sodium hydroxide method. Fifty-nine of 245
      (24%) clinical samples were culture positive for mycobacteria (43 M. tuberculosis
      complex, 12 M. avium complex and 4 other species) by one or both test systems.
      The MGIT detected 4 isolates of M. tuberculosis complex and 6 isolates of M.
      avium complex not recovered by the Ogawa egg medium, respectively. The mean time
      of detection of M. tuberculosis complex was 13 days (range: 2-26 days) and 19
      days (range: 8-31 days) for MGIT and Ogawa egg medium, respectively, and that of
      M. avium complex was 5 days (range: 2-8 days) and 16 days (range: 6-22 days) for
      the MGIT and Ogawa egg medium, respectively. Overall, the MGIT is a sensitive
      culture system for the detection of mycobacteria from clinical specimens, is easy
      to use and may be applicable to clinical laboratories.

PMID- 8753017
TI  - [Diagnosis of pulmonary aspergillosis in cases with cavity as sequela of
      tuberculosis].
AB  - Non-invasive pulmonary aspergillosis is frequently seen in cases with cavity as
      sequela of tuberculosis. Diagnosis of non-invasive pulmonary aspergillosis is not
      easy except for cases whose chest X-ray findings show a typical fungus ball. How
      to diagnose pulmonary aspergillosis was studied in 21 patients who showed changes
      in the radiological findings of cavity as sequela of tuberculosis. We made sputum
      culture of Aspergillus, measurement of precipitin antibody titer to Aspergillus
      fumigatus and measurement of PASTOREX ASPERGILLUS in serum and sputum on the 21
      patients (group A). PASTOREX ASPERGILLUS in sputum was evaluated in three grades:
      1+ approximately 3+. We diagnosed 14 patients as pulmonary aspergillosis (PA
      group) among the 21 patients taking into account the chest X-ray findings and the
      results of the above-stated investigations. The types of chest X-ray findings of
      these 14 patients were fungus ball type (FB) in 2 patients, productive
      aspergilloma on the inner wall of a cavity (PAIC) in 8, mixed type with FB and
      PAIC in 2 and non-specific change in 2. However, there were 3 patients with the
      chest X-ray findings suggestive of PAIC in 7 patients (non-PA group) who were not
      diagnosed as pulmonary aspergillosis. Sputum culture were positive in 11 patients
      of PA group (79%) and negative in all patients of non-PA group. Precipitin
      antibody were positive in 8 patients of PA group (67%) and negative in all
      patients of non-PA group. PASTOREX ASPERGILLUS in serum were negative in all 21
      patients. PASTOREX ASPERGILLUS in sputum were 3+ (+3) in all 14 patients of PA
      group and in 2 patients of non-PA group and 2+ (+2) in 2 patients of non-PA
      group. 12 patients of PA group were treated by antifungal agents and 11 patients
      responded well to the treatment. We also made sputum culture of Aspergillus and
      measurement of PASTOREX ASPERGILLUS in sputum on 14 patients (group B) who had
      respiratory diseases with stable cavities and 17 patients (group C) who had
      respiratory diseases without a cavity. In group B, sputum culture were positive
      in 1 patient and PASTOREX ASPERGILLUS in sputum were 3+ (+3) in 2 patients, 2+
      (+2) in 1 and 1+ (+) in 2. In group C, sputum culture were negative in all
      patients and PASTOREX ASPERGILLUS in sputum were 3+ (+3) in 1 patient, 2+ (+2) in
      3 and 1+ (+) in 2. Measurement of PASTOREX in sputum was a useful tool to
      diagnose non-invasive aspergillosis in addition to sputum culture and measurement
      of precipitin antibody titer. The sensitivity of PASTOREX in sputum was high but
      its specificity was low, however, its specificity could be raised by applying
      semi-quantitative analysis of PASTOREX in sputum.

PMID- 8753018
TI  - [A case of chronic tuberculous pyothorax associated malignant lymphoma].
AB  - The patient was 69-year-old male. He has a history of treatment for tuberculosis
      by artificial pneumothorax about 47 years ago. He was admitted an another
      hospital under the diagnosis of tuberculous pyothorax. He was transferred to our
      hospital because of chest pain and fever. Laboratory findings on the admission
      were as follows: ESR was 120 mm/hr, CRP was 20.22 mg/dl and other data were
      almost within normal limits. Chest X-ray showed a massive shadow in the right
      lower lung field, adjacent to the chest wall. Computed tomography (CT) showed
      tumor shadow with low density and invasions into the adjacent chest wall.
      Histological examination of surgically excised tumor biopsy revealed malignant
      lymphoma. The patient's condition improved and the size of tumor decreased
      temporarily by chemotherapy. Then, he began to complain of chest pain and high
      fever, and tumor in the chest wall invaded into the whole chest wall. He died of
      disseminated intravascular coagulation despite continuing chemotherapy.
      Postmortem examination revealed the following findings : the tumor existed mainly
      in the parietal pleura or the chest wall, adjacent to the lesion of pyothorax,
      and immunohistochemical examination showed that tumor was malignant lymphoma,
      diffuse, large B-cell type. Recent studies have shown a close association between
      EBV infection and pyothorax-associated lymphoma. We have to keep in mind the
      possible development of malignant lymphoma following tuberculous pyothorax, when
      we see patients complaining of fever or chest pain with tuberculous pyothorax.

PMID- 8753019
TI  - [Correlation between the nervous system and immune system].

PMID- 8753020
TI  - Experimental osteochondritis dissecans--the role of cartilage canals in chondral
      fractures of young rabbits.
AB  - Skeletal immature rabbits were used to study the pathogenesis of Osteochondritis
      Dissecans (OCD). Both histological studies and a radiographical examination were
      utilized after sagittal and coronal surgical chondral fractures were made in the
      femoral condyles cartilage. Serial microangiographies were performed in rabbits
      between 0 and 84 days after the chondral fractures were made. Analyses of the
      histology and microradiography findings suggest in either a coronal or sagittal
      direction, that avascular lesions like an experimental OCD occur as a sequence of
      chondral injury. A fracture in a wide pedicle of a stable cartilaginous flap with
      abundant cartilage canals heals in the usual way. However, a fracture in an
      unstable fragment with a small isthmus devoid of cartilage canals and of
      nutritious vessels, probably doesn't heal completely and a fragment closely
      resembling OCD is instead formed. An experimental OCD depends on the slender
      hinge of the flap and on the lack of stability in a rabbit's non-ossified
      epiphyseal cartilage. The damage to the cartilage canals and the rupture of
      vessels in the canals by a chondral fracture and the disturbance in the
      revascularization in the healing process by abnormal mechanical forces are thus
      most likely considered to be the main factor for OCD production.

PMID- 8753021
TI  - [Biodegradation of herbicide chlornitrofen (CNP) and mutagenicity of its
      degradation products].
AB  - Mutagenicities of three diphenyl ether-derived herbicides, chlornitrofen (CNP),
      nitrofen and chlormethoxynil, and their amino derivatives were assayed by the
      Ames test using TA98, TA100 and YG strains, recently developed tester strains. As
      for CNP, mutagenicities of its biodegradation products were also assayed, and
      biodegradation of CNP and change in mutagenic potency were examined using river
      water to which CNP was added. CNP was weakly mutagenic in YG1029, and nitrofen
      was weakly mutagenic in YG1029, while highly mutagenic in YG1026. But neither of
      three herbicides were mutagenic using TA98 and TA100. All of their amino
      derivatives were mutagenic especially in YG1024 and YG1029, acetyltransferase
      rich mutants of TA98 or TA100. In YG1029, mutagenic potency of the amino
      derivatives was relatively high compared with that of each parent compound.
      Concerning biodegradation products of CNP, amino-CNP was highly mutagenic and
      acethylamino-CNP was moderately mutagenic in YG 1026, but others were non
      mutagenic. In river water, CNP was degraded rapidly and converted to amino-CNP.
      Change in mutagenicity of river water to which CNP was added seemed to reflect
      changes in amino-CNP concentration in river water. Therefore, assessing health
      impact of chemicals released in natural environment, their degradation products
      must be considered along with parent compounds.

PMID- 8753022
TI  - [Limited operation and simple lobectomy for primary lung cancer in poor risk
      patients].
AB  - During the years 1990 to 1994, 54 poor risk patients were performed relative
      noncurative operation for primary lung cancer, such as limited operation or
      lobectomy without mediastinal lymphnodal dissection. The indication for lesser
      resection were mainly cardiopulmonary diseases and the elderly over 75 years old.
      3 were bilobectomies, 32 were lobectomies, 1 was lobectomy and segmentectomy, 10
      were segmentectomies, 8 were wedge resections. The number of cases with stage I
      were 41 (75.9%). Postoperative complications occurred in 13 patients (24.1%). The
      overall 5-year survival rate was 63.5%. The 5-year survial rate of p 0
      approximately p 1, pN 0 cases was 73.9%. Relative noncurative cases undergoing
      lesser resection showed relatively good result compared to standard lobectomy. It
      was considered that lesser resection for such poor risk patients with stage I can
      be a beneficial therapeutic modality.

PMID- 8753023
TI  - [A case of mucoepidermoid carcinoma underwent middle and lower sleeve bi
      lobectomies with carinal reconstruction].
AB  - A case of mucoepidermoid carcinoma was successfully resected by bronchoplasty
      with carinal resection. A 36-year-old male complaining cough and sputum was
      admitted to our hospital. Bronchofiberscopical examination revealed a tumor mass
      occluding the truncus intermedius. The tumor seemed to invade the carina, but the
      orifice of the right upper lobe bronchus was intact. The results of the
      pathological examination of the biopsy specimen showed mucoepidermoid carcinoma.
      Sleeve middle and lower lobe bi-lobectomies with carinal reconstruction were
      successfully performed. The postoperative course was uneventful. The patient is
      alive 5 year and 5 months after operation without recurrent tumor.

PMID- 8753024
TI  - [Echocardiographic evaluation of hemodynamic function of CarboMedics heart valve
      in the aortic position in patients with small aortic annuli].
AB  - Hemodynamic parameter of CarboMedics heart valve in the aortic position was
      evaluated using Doppler echocardiography in 46 patients with small aortic annuli.
      The size of prosthetic valve were 19 mm in 6 cases, 21 mm in 15 and 23 mm in 25.
      In patients with 19 mm valve, trans-valvular peak pressure gradient was 42.2 +/-
      11.8 mmHg, mean pressure gradient was 17.3 +/- 9.3 mmHg, and left ventricular
      systolic pressure was 174 +/- 12 mmHg. These values were significantly larger
      than those of the other two groups. Effective orifice area index, discharge
      coefficient, doppler velocity index and stroke volume showed no significant
      difference among each group. After aortic valve replacement for aortic stenosis,
      left ventricular mass decreased to around 70% of preoperative value in all
      groups, but significant left ventricular hypertrophy remained at two years
      postoperatively. We conclude that hemodynamic performance of CarboMedics heart
      valve in the aortic position was satisfactory, although 19 mm valve seemed to be
      fairly small for adult patients and deliberate patient selection is necessary.

PMID- 8753025
TI  - [Location of pulmonary nodules and evaluation of lymph node size by
      ultrasonography under thoracoscopy].
AB  - We evaluated the usefulness of ultrasonography under thoracoscopy for locating
      pulmonary nodules and measuring the size of mediastinal and hilar lymph nodes.
      Using unilateral lung ventilation with a double lumen tracheal tube,
      ultrasonography was effective in evaluating the condition of completely collapsed
      lungs. The locations of twelve nodules, including five lung cancers, six
      inflammatory lesions, and one intra-pulmonary lymph node, with sizes ranging from
      4 to 30 mm, were examined by ultrasonography. While all lung cancers and the
      intra-pulmonary lymph node were located by ultrasonography, only two of six
      inflammatory lesions were found. In examining mediastinal and hilar lymph nodes,
      all lymph nodes larger than 10 mm could be seen by ultrasonography. However, the
      ultrasonography could not distinguish between metastatic and non-metastatic lymph
      nodes. In conclusion, ultrasonography under thoracoscopy was able to locate
      pulmonary nodules larger than 10 mm, especially lung cancers, and was able to
      measure the size of mediastinal and hilar lymph nodes larger than 10 mm.

PMID- 8753026
TI  - [A proposal of a composite patch for early repair of ventricular septal
      perforation after acute myocardial infarction].
AB  - A 68-year-old female presented ventricular septal perforation (VAP) 3 days after
      acute myocardial infarction. The patient, supported with intraaortic balloon
      pumping, underwent surgical repair with success on day 15. At operation, the VAP,
      measuring 2.5 x 1.5 cm, was repaired using a composite patch consisting of Dacron
      felt and xenopericardium attached each other with fibrin glue. The composite
      patch was found really useful for repair of VSP in such early phase as when VSP
      sorrounding myocardium was very fragile, particularly in respect to the
      prevention of residual and/or recurrent shunt. This was because the composite
      patch was considered to have such excellent characteristics as: 1) toughness with
      sufficient compressibility and extensibility, 2) high antithrombogenesity and
      good tissue compatibility, 3) zero porosity, and 4) easy handling because of
      unification of two materials.

PMID- 8753027
TI  - [Surgically excised primary mediastinal tumors and cysts: a report of 43 cases].
AB  - Forty-three primary mediastinal tumors or cysts were surgically treated in 41
      patients during a 10-year period. These tumors consisted of 20 thymic tumors, 10
      neurogenic tumors, 5 teratomas, 3 lymphoid tumors, 2 congenital cysts, 2
      mediastinal thyroid tumors, and 1 chondroma. There were 16 male and 25 female
      patients. The mean age was 44 years with a range of 6 to 79 years. Sixteen
      patients (39%) were symptomatic. There were 20 thymic tumors including 13
      thymomas, 5 thymic cysts, and 2 hyperplasia with myastenia. Additional radiation
      therapy was recommended for all but stage I thymomas. Only 1 of the 10 neurogenic
      tumors was malignant. Eight teratomas were all cystic and matured. Early
      operative intervention is mandatory in these cases.

PMID- 8753028
TI  - [Surgery for acute type A aortic dissection associated with Marfan syndrome].
AB  - Recently, extended operation has been recommended for aortic dissection
      associated with Marfan syndrome. However, the operation for acute type A aortic
      dissection associated with Marfan syndrome is controversial. Between May 1985 and
      July 1994, 5 patients associated with acute type A aortic dissection and Marfan
      syndrome underwent surgical repair. CT examination on all patients, the survivors
      of the initial operation, revealed a gradually enlarged residual pseudolumen. 2
      patients who underwent aortic root reconstruction and ascending aortic
      replacement for the initial operation eventually had to undergo aortic arch
      repair. From the results of this study and the improvements of intraoperative
      cerebral protection, we recommend aortic arch repair with aortic root
      reconstruction and ascending aortic replacement on initial emergency operation
      for acute type A aortic dissection associated with Marfan syndrome.

PMID- 8753029
TI  - [Use of the inferior epigastric artery for coronary artery bypass grafting:
      preoperative digital subtraction angiography].
AB  - Between September 1994 and January 1995, the inferior epigastric artery (IEA) was
      used as a free graft for direct coronary artery bypass grafting in 4 patients.
      The IEA is excised from its origin from the external iliac artery as a pedicle
      with an "oval cuff" of 3 mm in diameter to facilitate the direct anastomosis with
      the aorta. The 4-week postoperative angiographic study showed that the IEA grafts
      were patent in all patients. We found that the IEA varies in length, diameter,
      and the pattern of branching between patients and between the right and left
      sides in the same patient. The preoperative digital subtraction angiography was
      useful for evaluating the suitability of IEA.

PMID- 8753030
TI  - [Surgical results of two cases of simultaneous carotid endarterectomy and
      coronary artery bypass grafting].
AB  - Reports on simultaneous revascularization operations for concomitant stenoses of
      the carotid and coronary arteries are many in Europe and America but few in
      Japan. Herein we report two cases of successful combined carotid endarterectomy
      and coronary artery bypass grafting. The first case was a 56-year-old male who
      had effort angina and a right carotid bruit with tinnitus. He was revealed to
      have severe stenosis of the right internal carotid artery as well as significant
      lesions of the right coronary artery. The second case was a 69-year-old male who
      had unstable angina and a left carotid bruit with a history of transient ischemic
      attack. Coronary angiography revealed three vessel disease and carotid digital
      subtraction angiography also revealed critical stenosis of the left internal
      carotid artery. In both cases, simultaneous carotid endarterectomy with an
      internal shunt and coronary artery bypass grafting were performed with a
      successful outcome. The use of internal shunt on reconstruction of the carotid
      artery was effective for protecting the brain.

PMID- 8753031
TI  - [Double chambered right ventricle in a 59-year-old man].
AB  - Surgical experience of double chambered right ventricle in a 59-year-old man was
      reported. The patient who had been pointed out for his systolic manner without
      any symptoms was admitted to our hospital because of heart failure. Cardiac
      catheterization revealed an about 80-mmHg peak-to-peak gradient in the right
      ventricle cavity with normal pulmonary pressure. Cineangiogram demonstrated
      double chambered right ventricle with perimembranous ventricular septal defect.
      Surgical repair with right ventriculotomy was performed in order to release
      pressure gradient and his symptoms. Right ventricular function after operation
      was not distorted. It is important to choose the surgical approach (right
      ventriculotomy or transatrial approach) for release the pressure gradient
      completely.

PMID- 8753032
TI  - [A case of ruptured sinus of Valsalva aneurysm with bicuspid aortic valve].
AB  - A 40-year-old male underwent operation with a suspected diagnosis of a ruptured
      of Valsalva aneurysm and a bicuspid aortic valve. The aneurysm with an apical
      rupture protruded into the membranous septum, between the leaflets of the
      tricuspid valve. The aortic valve was bicuspid, with the aneurysm originating
      from the right sinus of Valsalva. We presume that the bicuspid aortic valve tends
      to cause the sinus of Valsalva aneurysm in point that each coronary sinus is
      given excessive pressure compared with that in the normal aortic valve. Rarity of
      the combined cases is possibly because the bicuspid aortic valve is frequent
      while the sinus of Valsalva aneurysm is rare in Western countries and vice versa
      in Japan.

PMID- 8753033
TI  - [A case report of mitral valve papillary fibroelastoma leading to embolic
      stroke].
AB  - A 39-year-old man presented with acute onset of left arm and left side face
      weakness, and mild expressive aphasia. He was referred for two-dimensional
      echocardiography, which demonstrated a 13 mm diameter pedunculated, mobile,
      echodense mass attached to the anterior leaflet of the mitral valve. At
      operation, the tumor was a 10 x 10 x 15 mm, rounded, and yellow-whitish mass with
      a short stalk arising from rough zone of the anterior leaflet of the mitral
      valve. The surface appeared to be sean anemone. The mitral valve with this tumor
      was excised and replaced with a 29 mm St Jude Medical mechanical valve. The
      pathological findings are typical of a papillary fibroelastoma.

PMID- 8753034
TI  - [Surgical treatment for recrudescent Stanford type A early closing dissection].
AB  - Two cases of recrudescent Stanford type A dissection were reported. They had non
      opacified false channel on their initial CT and aortography. The first case was
      65-year-old woman having a stable blood pressure and no chest pain after
      admission. However, recrudescent opacified false lumen was found at the mid
      ascending aorta about three weeks later. She received ascending aortic
      replacement on 26th day after onset. The second case was 66-year-old woman having
      a unstable blood pressure and having periodic chest pain and back pain after
      admission. CT and angiography performed on the 41th day after onset revealed
      recrudescent descending aortic dissection and ulcer like projection at mid
      ascending aorta. The ulcer like projection increased in size gradually. Ascending
      aorta replacement was performed on 110th day after onset. Two cases had a good
      post operative days. Some cases of Stanford type A early closing aortic
      dissection had recrudescent dissection later, even if they had a stable course
      after onset. Thus, careful follow up for long term is essential in these cases

PMID- 8753035
TI  - [A case of redo operation for ascending aortic aneurysm after modified Bentall
      operation for Marfan syndrome associated with type A acute dissecting aortic
      aneurysm].
AB  - A 37-year-old man who had undergone modified Bentall operation in December 1986
      had redo operation for ascending aortic aneurysm. Initial operation, in other
      institute, included aortic root replacement using composite graft and
      reconstruction of coronary arteries. Left coronary ostium was directly
      anastomosed to composite graft while a saphenous vein was grafted between
      composite graft and right coronary artery concomitant with closing right coronary
      ostium. In addition, composite graft was wrapped with native aortic wall and
      Cabrol trick was carried out. In December 1994, this patient required redo
      operation for a 90 mm size of ascending aotric aneurysm which had been used for
      wrapping in the initial operation. The findings at reoperation revealed patent
      Cabrol trick, occluded saphenous vein graft, dehiscent proximal anastomosis of
      saphenous vein graft and partial dehiscence of distal anastomosis of composite
      graft. The repairs included new saphenous vein grafting to right coronary artery
      and re-anastomosis of distal site of composite graft. Cabrol trick was closed and
      composite graft was not wrapped. His post-operative course was excellent and post
      operative scintigram indicated ameriolation of inferior wall ischemia.

PMID- 8753036
TI  - [A case of coronary artery embolism after double valve replacement].
AB  - A 69-year-old woman with combined valvular heart disease (mitral regurgitation
      and aortic regurgitation), ascending aortic aneurysm, and atrial fibrillation
      underwent double valve replacement (DVR) and, ascending aortic wall plication.
      The postoperative thrombo-test level was around 20%. The ST elevation on ECG (II,
      III, aVFm, V4 approximately V6) with chest pain were recognized on the 13 th
      postoperative day. She was diagnosed as having acute myocardial infarction, and
      percutaneous transluminal coronary recanalization was performed immediately. The
      coronary angiogram showed occlusion at the left anterior descending branch (#8).
      This lesion could be recanalized by 6,000 U plasminogen pro activator (pro-UK)
      administration. The cineangiogram on the 35th postoperative day, revealed
      complete recanalization of this occlusion. Several cases of acute myocardial
      infarction associated with valvular heart diseases has been reported previously
      in Japan. However, there has been no report, except for this case, demonstrating
      occlusion in the coronary artery after prosthetic replacement and successful
      PTCR. So, this case is the first report on that point.

PMID- 8753037
TI  - [Case of intralobar pulmonary sequestration with increased serum sialyl Lewis X-i
      (SLX)].
AB  - A 37-year-old male whose chief complaint was fever and back pain was admitted to
      our hospital because of a mass shadow in the left lower P3ng field found in X-ray
      examination. The level of serum SLX on admission increased to 1,338 U/ml. He was
      diagnosed intralobar pulmonary sequestration by angiography. The left lower lobe
      was resected 2 months after second admission. His general condition was steady,
      and he was discharged 18 days after the operation because the level of serum SLX
      decreased to 49.9 U/ml.

PMID- 8753038
TI  - [A case of bilateral pneumothorax in the patient with Marfan syndrome].
AB  - A case of bilateral pneumothorax in the patient with Marfan Syndrome was reported
      13-year-old male was admitted to our hospital with diagnosis of left
      pneumothorax. He was tall and thin with long tapered extremities and echography
      revealed annulo-aortic-ectasia. A diagnosis of Marfan Syndrome was established by
      these characteristic of skeletal and cardiovascular findings. Air leakage
      continued inspite of the drainage of left chest cavity. Therefore, the resection
      of bullae was surgically undertaken. Post-operative course was uneventful and he
      discharged on 18th post-operative day. The pneumothorax of the right side
      occurred six months after first operation. After chest drainage, the surgical
      treatment was performed. However, he had recurrence of right pneumothorax six
      months after second operation. He was treated successfully with drainage tube and
      minocycline injection into the right pleural cavity. He should be carefully
      followed up, because the patient of Marfan Syndrome often dies due to
      cardiovascular abnormalities.

PMID- 8753039
TI  - [A case of inflammatory pseudotumor of the lung with suppressed immune response
      in the patient with renal cell carcinoma after nephrectomy and administration of
      interferon].
AB  - A 60-year-old man with renal cell carcinoma was treated of right nephrectomy and
      high dose administration of Interferon-alpha (IFN) in 1990. Three and half years
      after operation, he complained of cough and hemoptysis. Chest X-ray showed a
      abnormal shadow (5.5 x 3.5 cm) in the upper lung field. On chest CT, a tumor mass
      with small cavity was located at S2, attended with the speculation and pleural
      indentation. A rough nodule suspected daughter tumor was pointed out near the
      tumor mass. Laboratory investigation revealed mild leucocytosis, an elevated ESR
      and C reactive protein. On lymphocyte subset, CD 4/8 ratio was 0.8 and NK cell
      activity was 11%. Immunosuppressive acid protein (IAP) in serum was 1,137 ng/ml.
      No organisms or malignant cells could be demonstrated in the biopsy materials or
      sputum. Right thoracotomy and upper lobectomy was carried out. Postoperative
      pathological diagnosis was inflammatory pseudotumor. Namely, the lesion was
      occupied with variable admixture of lymphocytes, plasma cells, histiocytes,
      phagocytes included hemosiderin, foam cells and whorled fibrosis. Daughter tumor
      was scar tissue. Now, he is well without recurrence and his immune response is
      within normal level. Some discussion of the literature was mentioned.

PMID- 8753040
TI  - [A case of one stage operation for primary lung cancer and abdominal aortic
      aneurysm].
AB  - A 75-year-old male patient of primary lung cancer associated with abdominal
      aortic aneurysm was operated successfully in one stage. Right S2, S3 lung cancer
      was resected first and then aortic aneurysm was replaced with a Dacron graft.
      Both disease should be operated upon as early as possible. Low dose heparin usage
      did not disturb the operation. This case is the third reported case of one stage
      operation in Japan.

PMID- 8753041
TI  - [Reality and important points of whole and component blood transfusion].

PMID- 8753042
TI  - [Application and reality of erythrocyte transfusion].

PMID- 8753043
TI  - [Reality and clinical application of platelet transfusion].

PMID- 8753044
TI  - [Reality and clinical application of blood coagulation factor preparations].

PMID- 8753045
TI  - [Reality and clinical application of albumin preparation].

PMID- 8753046
TI  - [Reality and clinical application of immunoglobulin preparations].

PMID- 8753047
TI  - [Post-transfusion infections].

PMID- 8753048
TI  - [Post-transfusion GVHD].

PMID- 8753049
TI  - [Clinical application of erythropoietin].

PMID- 8753050
TI  - [Clinical application of neutrophil hematopoietic factors].

PMID- 8753051
TI  - [Clinical application of platelet hematopoiesis factor, thrombopoietin(c
      Mp1ligand)].

PMID- 8753052
TI  - [Hematologic diseases and blood transfusion].

PMID- 8753053
TI  - [Present status and future of blood management in Japan].

PMID- 8753054
TI  - [Effective utilization of blood in hospitals].

PMID- 8753055
TI  - [Bone marrow allograft using unrelated donor tissues].

PMID- 8753056
TI  - [Peripheral blood stem cell transplantation].

PMID- 8753057
TI  - [Blood transfusion therapy of hematological diseases (discussion)].

PMID- 8753058
TI  - [Case of bilateral retroperitoneal ganglioneuroma and renal artery abnormality
      with spasmodic hypertension, excessive catecholamine secretion after the removal
      of the tumor near right adrenal gland].

PMID- 8753060
TI  - [Differential diagnosis of Becker-type muscular dystrophy from polymyositis].

PMID- 8753059
TI  - [CA-19-9 antigen analysis of bronchoalveolar lavage fluid contributing to
      therapeutic decision of pulmonary alveolar epithelial tumor].

PMID- 8753061
TI  - [Sibling case of juvenile myocardial infarction caused by metabolic syndrome X].

PMID- 8753062
TI  - [Case of liver epithelioid hemangioendothelioma treated with percutaneous ethanol
      infusion].

PMID- 8753063
TI  - [Autoimmune diseases and cytokines].

PMID- 8753064
TI  - [Isolation of atopic genes].

PMID- 8753065
TI  - [Pharmacological studies on drug receptor mechanisms].
AB  - During the past ten years, the experiments based on the following three main
      propositions were carried out in our laboratory. (1) Drug receptor mechanisms. M3
      Cholinoceptors and alpha 1-adrenoceptors could be divided into two subtypes which
      were discriminated by beta-chloroethylamines only in the presence of GTP. The
      full agonists interacted with both subtypes to induce responses. The partial
      agonists activated one of them to induce responses but behaved as competitive
      antagonists when they interacted with the other. The responses mediated through
      the receptors which were activated by the partial agonists were resistant to
      myosin light chain kinase inhibitors, while the responses by the activation of
      the other receptors were suppressed by the inhibitors. The possible mechanisms
      for responses mediated through alpha 1-adrenoceptors and M3-cholinoceptors were
      discussed. beta-Adrenoceptors had also two binding sites, high and low affinity
      sites, which could be discriminated by the partial agonists. (2) Effects of
      ageing on drug receptor mechanisms. Potencies of alpha- and beta-adrenoceptor
      agonists increased from the young stage to the adult stage and decreased slowly
      thereafter to the old stage. The affinities of adrenergic drugs for their
      receptors did not alter with ageing. The changes in the adrenoceptor-mechanisms
      with ageing were mainly due to the changes in the amount of receptors. However,
      the decrease in the potency of beta-agonists in the preparations from the older
      animals was due to the change in the post beta-receptor processes in
      responsiveness. No age-related change was observed in serotonin, acetylcholine
      and tachykinin receptor mechanisms. However, the potencies of acetlcholine and
      tachykinin were modified by the change in the activity of related enzymes, which
      altered with ageing. (3) Drug design. Taking into account pharmacological studies
      on opioid receptors, N-cyclopropylmethyl normorphine derivatives were
      synthesized. They had more potent analgesic action than morphine through the
      activation of kappa-opioid receptors. They might not possess dependence
      liability.

PMID- 8753066
TI  - [Studies on development of disulfide bond forming reaction and the application to
      regioselective disulfide formation].
AB  - An efficient method for the disulfide bond formation in peptides by the
      silylchloride-sulfoxide system is described. Methyltrichlorosilane in
      trifluoroacetic acid, in the presence of diphenylsulfoxide, is found to cleave
      various S-protecting groups of cysteine to form cystine directly within 10 to 30
      min. No side reactions were observed with nucleophilic amino acids such as Met,
      His, or Tyr, except for Trp, under the reaction conditions of the silylchloride
      sulfoxide treatment. A chlorination of the indole moiety of unprotected Trp,
      rather than the sulfur-sulfur bond formation, is a dominant reaction when the
      peptide containing unprotected Trp is treated with the chlorosilane-sulfoxide.
      However, the disulfide bond can be formed efficiently with no modification at the
      indole ring by the treatment of the peptide having formyl-protected Trp residue
      with the silylchloride-sulfoxide system. The formyl group is removed by a brief
      treatment at basic pH without affecting the disulfide bond formed by the
      silylchloride-sulfoxide treatment. Total synthesis of human insulin, a two chain
      peptide containing three disulfide bonds, was achieved unambiguously by
      sequential and selective formation of disulfide bonds in the protein for the
      first time. The key reaction in the synthesis is regioselective formation of
      three disulfide bonds separately using the silyl chloride method described above.
      Prior to the insulin synthesis, it was confirmed by the syntheses of double
      disulfide peptides: b-hANP, unnatural parallel dimer of a-hANP, and human
      endothelin-1 that no disulfide exchange occurred during the silyl chloride
      treatment. Using three orthogonal thiol protecting groups, Trt, Acm, and But,
      three disulfide bonds of human insulin were efficiently constructed by the
      successive reactions using thiolysis, iodine oxidation, and the sily1 chloride
      method. Each reaction for the stepwise disulfide formation proceeded within 15 to
      60 min with no polymeric product and no solubility problem. The synthetic human
      insulin had the correct structure and was indistinguishable from natural human
      insulin.

PMID- 8753067
TI  - [Nutritional and biochemical studies on vitamin D and its active derivatives].
AB  - We have performed nutritional and biochemical studies on vitamin D and its active
      derivatives and the following results are obtained. 1. Since recent studies have
      revealed that dietary supplement of vitamin D (D2 and D3) and calcium is
      effective for preventing osteoporosis, a simplified routine method for
      determination of vitamin D in foods is established and applied to the assay on
      the contents of vitamin D in various kinds of Japanese foods. 2. A simplified
      routine method for simultaneous determination of vitamin D and its metabolites in
      the plasma and milk is established and applied to nutritional and clinical
      studies. 3. Physiological activities of two kinds of novel vitamin D3
      derivatives, 22-oxa-1 alpha, 25-dihydroxyvitamin D3 (22-oxa-1,25(OH)2D3, OCT) and
      2 beta-(3-hydroxypropoxy)-1,25(OH)2D3 (ED-71) have been studied. OCT, which has
      less calcemic and stronger cell differentiation activities than 1,25(OH)2D3, is a
      candidate for curing leukemia and other cancers without hypercalcemia. We have
      clarified that the property is due to its weak binding affinity for vitamin D
      binding protein and rapid turn-over in the body and rapid excretion into bile. On
      the other hand, ED-71, which has stronger effects on intestinal calcium
      absorption and longer bone turn-over than 1,25(OH)2D3, is a candidate for curing
      osteoporosis. We have clarified that the properties are due to stronger binding
      affinity for DBP and longer half-life than 1,25(OH)2D3.

PMID- 8753068
TI  - [Development of HPLC packing materials for drug analysis and their applications].
AB  - High-performance liquid chromatography (HPLC) has been used for the assays of
      pharmaceuticals and their impurities, and drugs and their metabolites in
      biological fluids. However, HPLC packing materials so far developed are not
      necessarily suitable for the above mentioned purposes. During the past decade, we
      developed of new HPLC packing materials for direct serum injection analysis of
      drugs, and for chiral resolution of drug enantiomers. A sample preparation step
      such as deproteinization and/or extraction is required for HPLC assays of drugs
      and their metabolites in biological fluids. Direct serum injection analysis of
      drugs can be achieved by the use of the packing materials having properties as
      follows: large molecules such as proteins are eluted in the void volume without
      destructive accumulation, but small molecules such as drugs and their metabolites
      can reach the hydrophobic sites and be separated. Such a material is called
      restricted access stationary phase (RASP). We developed two RASPs, an improved
      internal-surface reversed-phase (ISRP) material and a mixed functional phase
      (MFP) material. The preparation methods of the ISRP and MFP materials and their
      applications to the assays of drugs in the serum are described. HPLC chiral
      stationary phases based on chiral small molecules, and macromolecules such as
      polysaccharides and proteins have been used for separations of drug enantiomers.
      Disadvantages of protein-bonded stationary phases include low capacity, lack of
      column ruggedness and limited understanding of the chiral recognition mechanism.
      We tried to overcome the disadvantages of protein-bonded stationary phases by
      modification of side-chain amino acid and preparation of protein-domain or 
      fragment column. We isolated each ovomucoid domain and examined chiral
      recognition ability of each domain. The ovomucoid third domain exhibited chiral
      recognition for only a few benzodiazepines and 2-arylpropionic acid derivatives.
      The chiral binding site and mechanism on the ovomucoid third domain was
      investigated by proton NMR measurements and molecular modeling of the ligand
      protein complex. Further, new protein, ovoglycoprotein, was isolated from crude
      ovomucoid preparations, characterized and bound to silica gels. It was found that
      the chiral recognition ability of the ovomucoid reported previously came from the
      ovoglycoprotein, which is present in crude ovomucoid as an impurity.

PMID- 8753069
TI  - [Synthesis and antibacterial properties of quinoxaline 1,4-dioxide derivatives].
AB  - Novel quinoxaline 1,4-dioxide derivatives were synthesized from benzofuroxans and
      the enolic form of 1,3-diketones or 3-oxoalkanoic esters or 3-oxoalkanamides or
      butanedioic esters catalyzed by silica gel or molecular sieves and their
      antibacterial activities were evaluated. As the results of antibacterial
      screening tests in vitro, quinoxaline 1,4-dioxides revealed strong activities
      against Bacteroides fragilis.

PMID- 8753070
TI  - [The transport of enoxacin in cultured kidney epithelial cells LLC-PK1].
AB  - In this study, the transport of enoxacin (ENX) was investigated in a LLC-PK1
      kidney epithelial cell line. The uptake of ENX by LLC-PK1 monolayers cultured in
      plastic dishes was shown to be temperature-dependent and concentration-dependent.
      Cimetidine and guanidine inhibited the uptake of ENX, whereas TEA and NMN did
      not. The basolateral to apical flux of ENX across LLC-PK1 monolayers cultured on
      permeable supports was about two times larger than the apical to basolateral
      flux. The basolateral to apical flux of ENX was remarkably inhibited by
      guanidine, whereas it was not inhibited by TEA, NMN and cimetidine. The apical to
      basolateral flux of ENX was inhibited by cimetidine and guanidine, whereas it was
      not inhibited by TEA and NMN.

PMID- 8753071
TI  - [Articulatory function in patients receiving glossectomy followed by
      reconstruction with a recto-abdominal myocutaneous free flap].
AB  - Postoperative articulatory functions of patients with tongue cancer have been
      improved by reconstructive surgery with a radial forearm or recto-abdominal
      myocutaneous free flap. We examined the postoperative articulatory functions of
      10 patients who received reconstruction with a recto-abdominal myocutaneous free
      flap after glossectomy. The functions were investigated by standardized tests, i.
      e. a quentionnaires, the 100 Japanese monosyllable speech intelligibility test
      and a single-word intelligibility test. A confusion matrix was obtained from the
      results of the monosyllable test. On the basis of resection sites, the present
      cases were divided into two types: an anterior type and a lateral type. The
      results are summarized as follows. There was no significant difference in the
      results of the quentionnareis between the two types. The mean score of the 100
      Japanese monosyllable speech intelligibility test in cases of the anterior type
      was 48% and in those of the lateral type it was 62%. The mean score of the single
      word intellibibility test in cases of the anterior type was 75% and in those of
      the lateral type it was 83%. In cases of the anterior type, dental and alveolar
      sounds were often confused with fricatives, whereas in the lateral type, velars
      sounds were often confused with affricates or flaps. These results suggest that
      our classification based on resection site was useful for investigating
      postoperative articulatory functions after partial glossectomy.

PMID- 8753072
TI  - [Hearing acuity in the elderly in Japan].
AB  - In Japan, the elderly population has progressively increased. It is therefore
      expected that various social services for the elderly will be demanded. As most
      of the elderly have hearing impairment due to presbycusis, it is difficult to
      communicate smoothly with them. To provide the various social services, it is
      necessary to investigate hearing acuity in the elderly. Accordingly, the Hearing
      Research Group, which belongs to the Research Project on Aging and Health in the
      Ministry of Health and Welfare of Japan, investigated the hearing acuity of
      people 65 years old, or more. One thousand one hundred ninety two subjects were
      divided into five groups, Group A consisted of 170 males and 216 females between
      65 and 69 years old, Group B, 186 males and 158 females between 70 and 74; Group
      C, 147 males and 140 females between 75 and 79; Group D, 63 males and 61 females
      between 80 and 84; and Group E, 29 males and 22 females 85 years old or more. We
      examined the 175 subjects 80 years old or more. Therefore, it is considered that
      this study could indicate the present condition of hearing acuity of the elderly
      of Japan. The average hearing levels measured at seven frequencies (125, 250 and
      500Hz, and 1, 2, 4, and 8KHz) were 35.0dB in group A, 42.1 in group B, 46.1 in
      group C, 52.1 in group D, and 55.6 in group E. There were no differences in the
      average hearing level between males and females in any group. The audiogram
      pattern indicated a gradually descending curve in most subjects in all groups.
      The average speech discrimination rate was 75.4% in group A, 70% in group B,
      63.8% in group C, 59.7% in group D, and 52.1% in group E. The percentage of
      subjects showing a short increment sensitivity index of more than 70% was 45.2%
      in group A, 49.3% in group B, 47.9% in group C, 51.6% in group D, and 59.7% in
      group D. In conclusion, hearing loss due to aging tended to be more progressive
      at higher frequencies while hearing acuity of frequencies covering normal speech
      was preserved. However, the speech discrimination rate decreased relative to
      changes in the pure tone hearing level. It was considered that the pathology of
      hearing loss due to aging begins with retrocochlear changes and cochlear factors
      are added to retrocochlear changes with aging.

PMID- 8753073
TI  - ["Vertigo" the fact analysis of clinical practice by ENT physicians of Chiba
      Prefecture by "send-out" questionnaires].
AB  - Despite the fact that vertigo has been one of the most frequent complaints
      encountered in daily practice in an ENT outpatient clinic, it is believed to be
      the most unwelcome subject for ENT physicians. The reasons are diverse; e.g., the
      understanding of vertigo is still a difficult task for most physicians and
      requires time-consuming multiple studies. However, answers to those questions,
      although speculated a posteriori, are yet to be substantiated. Therefore, we have
      analyzed the data obtained from multiple questionnaires that were addressed to
      ENT physicians practicing in Chiba Prefecture in November of 1993. However, those
      who work in publicly run hospitals were excluded from the study. The study
      included otorhinolaryngologists who were members of the Society of
      Otorhinolaryngology of Japan. We received filled questionnaire forms from 76 of
      155 members (49%). The age ranged from 33 to 82 years (mean 55.8 years, 68 men
      and 8 women). From these questionnaires, it became apparent that physicians are
      not necessarily reluctant to see patients with vertigo. Instead, most ENT
      physicians appeared to be actively paying attention to this symptom and to be
      making efforts to approach its diagnosis and treatment. Although we are not
      certain if the data obtained here represent the majority of ENT physicians, the
      positive attitudes toward the patients with vertigo/dizziness would certainly
      encourage those of us who are interested in this particular symptom category.

PMID- 8753074
TI  - [Effects of chronic electrical stimulation on cochlear nuclear neuron size in
      deaf kittens].
AB  - It is now well recognized that normal afferent innervation is necessary for
      development of the auditory pathway. This study investigated the effect of
      chronic electrical stimulation of the auditory nerve on the size of cochlear
      nucleus somata of neonatally deafened kittens. Four kittens were deafened by
      using kanamycin and ethacrynic acid at 10 days of age and implanted at various
      ages with an active intracochlear implant in the left side and a dummy implant in
      the right side, and chronically electrically stimulated from ages 98-142 days for
      approximately 1000 hours at twice the EABR threshold. After chronic stimulation
      or after an equivalent period in the controls, the animals were injected with 2
      deoxyglucose (2DG) and stimulated electrically for 45 minutes, then processed for
      autoradiography. Then the sections were stained for Nissle substance, and the
      cross-sectional areas (CSSA) of approximately 33,000 neuron somata in the
      cochlear nuclei were measured with an image-analysis system. Soma sizes in
      regions with 2DG uptake were compared with those without the uptake. The CSSA of
      2DG-labeled regions was usually significantly larger than that of the unlabeled
      regions, but there were no significant right-left differences. Thus, chronic
      electrical stimulation of a restricted sector of the cochlea is correlated with a
      larger soma size in the corresponding region of the cochlear nucleus.

PMID- 8753075
TI  - [Mechanism of volume regulation of vestibular dark cells of the gerbil].
AB  - The volume response of vestibular dark cells of the gerbil to a hyposmotic
      challenge was investigated. Tissues including dark cells were perfused in
      preparations in which the perfusate had access to both sides of the epithelium
      and the height of the dark cell layer was measured as an indicator of its volume.
      We found that dark cells showed a fast and strong regulatory volume decrease
      (RVD) and prevented cell swelling in hypotonic media. This mechanism was
      dependent upon extracellular [K+] and [Cl-]. Ion selectivity of this mechanism
      was K+ = Rb+ > Cs+ > Na+ = NMDG+ (N-methyl-D-glucamine) for cations and Cl- = SCN
      = NO3- > > gluconate- for anions. RVD of dark cells was inhibited by K(+)-
      channel blockers barium, quinidine and lidocaine, by Cl(-)-channel blockers 4
      acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid and 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid, by an Na(+)-K+ ATPase inhibitor
      ouabain and by low temperature, but was not inhibited by a loop diuretic
      bumetanide, by carbonic anhydrase inhibitors acetazolamide and ethoxyzolamide, by
      a K(+)-channel blocker tetraethylammonium, by a Cl(-)-channel blocker 5-nitro-2
      (3-phenylpropylamino)-benzoic acid or by an inhibitor of the Na(+)-H+ exchanger
      amiloride. These data suggest that the RVD of dark cells occurs via separate K+
      and Cl- channels which are different from those active under isosmotic condition,
      and is presumably activated by a hyposmotic stimulus.

PMID- 8753076
TI  - [A case of Paget's disease with progressive sensorineural hearing loss involved
      in the bilateral bony labyrinths].
AB  - Paget's disease of the bone is a chronic, progressive disease of unknown etiology
      characterized by abnormal bony resorption and deposition. It is a common skeletal
      disease in Europe and North America, while in Japan it is very rare. Paget's
      disease of the temporal bone has been reported to cause hearing loss frequently.
      We report a 50-year-old woman with Paget's disease who had progressive bilateral
      sensorineural hearing loss and right vestibular dysfunction. CT and 3 Dimensional
      CT (3D-CT) images demonstrated resorption of the entire bony labyrinth and its
      surroundings on both sides and that the temporal bone elsewhere remained intact.
      Bone scans revealed disease symmetrically in the bilateral otic capsules.
      Previous studies indicated that the bone changes in Paget's disease in the
      petrous pyramid begin in areas best supplied with marrow tissue and that the otic
      capsule is relatively spared until advanced changes are present in the remainder
      of the petrous pyramid. But, this patient mainly had foci in the bilateral otic
      capsules and the pattern was similar to cochlear otosclerosis. 3D-CT was useful
      for differentiation of Paget's disease and cochlear otosclerosis. The pattern of
      the affected areas indicated that this is a very rare situation even in the
      reports of Europe and North America, where the disease is rather common.

PMID- 8753077
TI  - [Study of malignant lymphoma in the parotid gland region].
AB  - Malignant lymphomas arising in the salivary glands are very uncommon. The vast
      majority of these lesions are classified as extranodal non-Hodgkin's lymphoma.
      Clinical presentation, management, histopathology, and outcome in 11 cases of non
      Hodgkin's lymphomas of the parotid gland region were reviewed. The ages of the
      patients ranged from 25 to 80 years (average 56.0 years) and the male to female
      ratio was 5:6. Presenting symptoms were painless masses (10 cases) and a painful
      mass (1 case) in the parotid gland region. None of the patients had facial nerve
      paralysis. It seems to be difficult to diagnose malignant lymphomas of the
      salivary glands preoperatively, because an open biopsy of the salivary glands is
      generally contraindicated. We failed to diagnose malignant lymphoma in the
      parotid gland preoperatively. The clinical stages were stage I in 5 cases, stage
      II in 5 cases, and stage III in 1 case. There was no patient with stage IV. Three
      of the stage I tumors were diagnosed as MALT (mucosa-associated lymphoid tissue)
      lymphomas. Eight of the tumors were treated surgically and an open biopsy of the
      parotid gland tumor was performed in 1 case and open biopsy of a neck lymph node
      in 2 cases for the purpose of diagnosis. After the diagnosis, these cases were
      followed up with or without radiotherapy and chemotherapy. Follow-up ranged from
      6 to 109 months. The 5-year-survival rate was 60%. The outcome for this group was
      found to be as good as that reported by others.

PMID- 8753078
TI  - [Comparison of measuring an area with a planimeter and by rectangular dimensional
      methods].
AB  - We have developed a system that measures the volume of air cells in the temporal
      bone through computerized digital processing of high-resolution CT images. By
      using this method, the volume of pneumatization was measured, and the results
      were compared with the measured area of pneumatization obtained from two
      conventionally used simple ear X-ray methods (the planimeter and rectangular
      dimensional methods). A total of 57 ears, from 34 subjects, confirmed as normal
      by CT were examined. The average volume of pneumatization measured on CT images
      was 5.97 +/- 4.15ml, and the average areas of pneumatization measured by the
      planimeter and rectangular methods were 9.08 +/- 5.64 and 17.39 +/- 9.77 cm2,
      respectively. Graphically, when the volume of pneumatization was plotted on the Y
      axis and the planimeter-measured area of pneumatization on the X axis, a
      regression formula of Y = 0.651X + 0.054 was obtained, with a correlation
      coefficient of 0.89. With the volume of pneumatization plotted on the Y axis and
      the rectangular-dimensional-measured area of pneumatization on the X axis, the
      regression formula was Y = 0.375X - 0.559, with a correlation coefficient of
      0.88. Both these correlation coefficients were considered high. Furthermore, 3D
      models of the air cells in the temporal bone were created and compared for
      patients with high and low correlations. In order to capture the morphological
      characteristics of these 3D models, they were examined from four different angles
      (lateral, upper lateral, anterior lateral and upper medial). The results showed
      that regardless of whether air-cell growth was present in the direction of the
      apex partise petrosae in patients with a low correlation coefficient, such growth
      played a major role in the degree of the correlatiton. Future studies will be
      required to clarify this point, though it can already be said that 3D models are
      indispensable for studying the air cells in the temporal bone. When we compared
      the volume and area of pneumatization in the temporal bone at different CT cross
      sections, we found correlation coefficients in the vicinity of the canalis
      semicircularis lateralis of about 0.9 or higher. A statistical comparison of
      correlation coefficients for the CT, planimeter, and rectangular dimensional
      methods, made by using the CT cross-section with the highest coefficient, found a
      significant difference between the CT method and the other two methods (p <
      0.05). In other words, the volume of pneumatization can be estimated more
      accurately with CT images than with simple ear X-rays.

PMID- 8753079
TI  - [Morphological study of laryngeal ganglions and associated nerve cells in humans
      and five mammals].
AB  - The arrangement and numbers of intralaryngeal ganglia and associated neurons in
      humans and four mammals (dogs, rabbits, guinea pigs and rats) were investigated
      morphologically and compared with the results obtained in the cat which have been
      reported previously. Intralaryngeal ganglia were mostly distributed in branches
      of the internal branch of superior laryngeal nerve in all species, dorsal and/or
      dorsolateral to the posterior cricoarytenoid muscle in humans, dogs and cats and
      around the inferior laryngeal nerve in humans, dogs, cats, guinea pigs and rats.
      The total number of laryngeal ganglionic neurons was 2,000 to 2,400 in humans,
      300-450 in dogs, 600-800 in cats, 250-320 in rats, and 100-150 in rabbits and
      guinea pigs. More than 80 percent of ganglionic neurons were present in the
      supraglottis in all species, except the rat, in which about 60 percent were in
      the subglottis. Each ganglion in all species existed within the nerve bundle, and
      was chiefly encapsulated with fibrous tissue, many ganglionic cells, glial cells,
      Schwann cells, vessels and connective tissue. The present morphological study of
      intralaryngeal ganglia in humans and four mammals suggests that the laryngeal
      ganglionic neurons have the same arrangement as in cats.

PMID- 8753080
TI  - [Changes with aging in ECochG].
AB  - The present study was designed to determine the standard values of AP, adapted AP
      and CM (0.5, 1, 2, and 4kHz) of the electrocochleogram using subjects with normal
      hearing (20 ears, mean subject age 30.4 years). The input-output function, the
      latency and the threshold were measured in AP, whereas only an input-output curve
      was made for the adapted AP and the input-output function and the threshold were
      measused in CM. The CM threshold had the highest positive correlation with the
      threshold of the conventional pure tone audiometry at 1kHz. These standard curves
      will be very useful for analysing clinical data. In order to discuss the aging
      changes affecting electrocochleograms, the test subjects were divided into two
      groups, i.e. one group was composed of subjects under 30 years of age (mean: 19.7
      y/o, 10 ears) and the other of those 30 years old or over (mean: 41.1y/o, 10
      ears). There were no differences in hearing threshold or the threshold of the
      electrocochleogram between the two groups. The CM threshold exhibited the highest
      positive correlation with the threshold of conventional audiometry at 1kHz in
      both groups. AP and adapted AP showed no difference in any item between the two
      groups. Although there was no difference in the CM threshold, there was an
      obvious difference in the CM input-output curves between these two groups at high
      stimulus intensities of 2 and 4kHz. It is known that the EP decrement makes CM
      smaller. However, it is unlikely that this decreased CM response in the older
      group was due to EP suppression, since this phenomenon was only observed in
      response to high intensity stimulo and there was no difference in responses to
      low intensity stimulo. Another possible explanation for this phenomenon is aging
      changes in the basilar membrane, tectorial membrane and hair cells. Further
      studies are necessary to elucidate the etiology of the CM suppression revealed in
      the present study.

PMID- 8753081
TI  - [Peri- and postoperative courses in patients undergoing concomitant cardiac and
      pulmonary operations].
AB  - We studied peri- and postoperative courses in patients undergoing concomitant
      cardiac and pulmonary operations (CCPO), which included pulmonary resection and
      coronary artery bypass grafting (CABG). Of eight patients who had lung cancer and
      ischemic heart disease (IHD), six underwent CCPO and two patients first had
      percutaneous transluminal coronary angioplasty (PTCA) followed by lung surgery at
      an interval after the first procedure. Twelve patients with lung cancer who
      underwent only pulmonary surgery and 13 patients with IHD who were treated with
      CABG were studied as controls. We compared peri- and postoperative
      characteristics among these groups of patient. Operating time, bleeding volume
      during surgery, amount of drainage discharge within 24 hours after the operation,
      and ICU days were significantly increased in the CCPO group in comparison with
      the two control groups. In the CCPO group, mechanical ventilatory support time
      and administration days after the operation were significantly increased in
      comparison with the lung operation group, but not in comparison with CABG group.
      The two patients who sequentially underwent PTCA and lung surgery had
      postoperative courses similar to the CCPO patients. All CCPO patients were
      ambulatory upon discharge. None of the CCPO patients died from postoperative
      complications involving the respiratory tract or the circulatory system. Our data
      suggest that CCPO is available for patients with both heart and lung diseases
      when complications can be avoided by appropriate management, although these
      procedures are extremely invasive. We believe that CCPO should be attempted in
      patients with definite indications for such a procedure.

PMID- 8753082
TI  - [Hypothermic management of brain dead dogs].
AB  - For preventing graft failure, the effects of hypothermic management of brain dead
      dogs was investigated. Forty-three brain dead dogs were divided into two groups
      according to the degree of esophageal temperature; a normothermic group (37.2 +/-
      0.3 degree C, mean +/- SEM, n = 22), and a hypothermic group (31.8 +/- 0.3 degree
      C, n = 21) which was obtained by introducing ice slush in the peritoneal cavity.
      During the management of brain dead dogs, 1) heart rate, pressure product, and a
      total amount of catecholamine were significantly lower (p < 0.05) in the
      hypothermic group than in the normothermic group, 2) mean blood pressure, the
      maximum rate of the rise of left ventricle (LVdp/dt) and cardiac output were not
      different between both groups, 3) lactate content in the coronary sinus, and O2
      extraction rate of the heart tended to be lower in the hypothermic group than in
      the normothermic group. After transplantation, the recovery of cardiac function
      was better in the hypothermic group than in the normothermic group. Hypothermic
      management of brain dead dogs may safely decrease cardiac stress, and keep
      cardiac aerobic circumstances.

PMID- 8753083
TI  - [The earlier detection of myocardial damage in open heart surgery using serum
      human heart fatty acid-binding protein].
AB  - Human heart fatty acid-binding protein (HH-FABP), which is a low molecular weight
      protein and abundant in the cytoplasm of myocardial cells, is reported to be
      released into the circulation shortly after the onset of acute myocardial damage.
      However, the changes in serum HH-FABP levels in open heart surgery have not been
      elucidated. To determine whether HH-FABP enables the earlier detection of
      myocardial damage caused by ischemia-reperfusion in open heart surgery, we
      measured the serial levels of serum HH-FABP, CK-MB and Troponin T (TnT) at every
      15 min for 48 hours after reperfusion in 10 adult patients with coronary artery
      bypass graft. The serum HH-FABP levels reached the peak within 60 min after
      reperfusion (mean +/- SD; 49 +/- 7 min), and this was significantly (p < 0.001)
      earlier than CK-MB (212 +/- 108 min) and TnT (244 +/- 150 min). The peak value of
      serum HH-FABP had a significant correlation to the peak value of serum CK-MB or
      TnT (r = 0.815, p = 0.02; r = 0.925, p = 0.0001, respectively). These results
      indicate that serum HH-FABP enables the earlier detection of myocardial damage
      than the other markers in the patients with open heart surgery.

PMID- 8753084
TI  - [Aortic root replacement employing Cabrol and Piehler techniques].
AB  - Between February, 1982, and September, 1994, 24 patients underwent aortic root
      replacement using a valve-bearing composite graft and coronary perfusion grafts.
      The indications for surgery were annulo-aortic ectasia in 21 patients, and aortic
      dissection associated with significant aortic regurgitation in 3 patients. Aortic
      root was reconstructed employing the techniques described by Cabrol and
      colleagues (Cabrol operation) in 16, and by Piehler and Pluth (Piehler operation)
      in 8. Two of 16 patients who underwent Cabrol operation required concomitant
      procedures. Four patients (25.0%) who underwent Cabrol operation had technical
      troubles relating to coronary reattachements (kinking and torsion of coronary
      grafts in 2, obstruction of left limb of coronary graft in 1, and coronary graft
      compression by aortic wall wrapping in 1), while one patient (12.5%) having
      Piehler operation had coronary graft compression by partial wrapping of aortic
      root. The hospital deaths occurred in 4 patients undergone Cabrol operation, with
      the hospital mortality rate being 16.7%. Three patients including 2 with
      concomitant procedures died of low cardiac output and one died of rupture of
      residual dissecting aneurysm of the aortic arch. No pseudoaneurysm nor
      anastomotic stenosis was observed in any hospital survivors. Late deaths occurred
      in 5 patients, in whom there was no late complication relating to coronary
      reconstruction. However, late obstruction of left ostial stenosis developed in
      one patient who underwent Piehler operation, which required coronary artery
      bypass. We conclude that aortic root replacement using coronary perfusion grafts
      provides sound coronary anastomoses without late pseudoanurysm. Coronary
      reattachments is facilitated by use of Piehler technique, preventing coronary
      graft kinking or torsion. Late coronary ostial stenosis should be considered as a
      possible cause of fatal myocardial infarction and sudden death, and careful
      follow-up is required for patients having these kinds of operation for the
      prevention of late cardiac events.

PMID- 8753085
TI  - [The efficacy of pyloroplasty affecting to oral-intake quality of life using
      reconstruction with gastric tube post esophagectomy].
AB  - After resection of esophageal carcinoma, pyloroplasty was undergone due to vagal
      denervation. Especially the ability of oral-taking is related to the return of
      general societies after operation. This was a randomized study on whether
      pyloroplasty was effective by functional and nutritional evaluations. From 1992
      to 1995, 67 patients with esophageal carcinoma underwent subtotal esophagectomy
      and reconstruction using a gastric tube. Thirty-four patients were randomized
      into the pyloroplasty group (P), and 33 into the control group (N). The
      functional evaluation was done with (1) food-taking scoring (2) A foods with
      barium granules ejection time (3) a gastric emptying time of 99m Technecium (4)
      75 g OGTT. The nutritional evaluation were (1) Rapid Turn-over Protein (RTP) (2)
      Total Lymphocyte Count (TLC) (3) ONODERA's Prognostic Nutritional Count (PNI) (4)
      Fluctuation rate of body weight. The elevations were performed 1 and 6 months
      after operation. Functional evaluation were as follows. (1) Quantity of oral
      intake was not significant different between (P) and (N) both improving those
      quantities in 6 months. Regarding several complaints including in regurgitation,
      (P) had a few symptoms comparing to (N), almost half of cases complained of some
      symptoms and did not improving in 6 months. (2) The food ejection time of foods
      were 19.6 +/- 31.0 min, in (P), 32.9 +/- 37.2 min, in (N), (3) In the Tc gastric
      emptying time, we calculated as 50% ejecting time and residual rate of 30 min. In
      50% ejecting time less than 20 min., (P) shared in 65, 80%, (N) in 39, 40% in 1
      and 6 months. (4) In 75 g OGTT there were no significant difference between both
      groups, though several cases showed the dumping syndrome. In the nutritional
      evaluation, in RTP, TLC, PNI, and postope, body weight, there were no differences
      between the two groups. In conclusion, pyloroplasty several symptoms related to
      oral intake including regurgitation feelings, and in functional evaluation, there
      shows faster gastric emptying though there were no significant differences in the
      nutritional phases at 6 months follow-up. The results suggest that this procedure
      is not essential but it affects to the oral-intake QOL effectively.

PMID- 8753086
TI  - [Continuous systemic venous oxygen saturation monitoring immediately after Fontan
      procedure].
AB  - Changes in cardiac output (CO), systemic venous oxygen saturation (SvO2),
      systemic oxygen consumption, and urinary output immediately after Fontan
      procedure were measured in 10 patients at the intensive unit (ICU) to assess the
      effects of aorusal from anesthesia, hypothermic management, and respiratory
      condition. The measurements were taken at the following phases; phase A in deep
      sedation under hypothermia (33-35 degrees C rectal temperature) and controlled
      ventilation; phase B in mild sedation under normothermia and controlled
      ventilation; phase C when awake under normothermia and assisted ventilation;
      phase D when awake under assisted ventilation; phase D when awake under
      normothermia immediately after extubation; and phase E 24 hours after extubation.
      Oxygen delivery (O2 Del.) and fractional oxygen fractions were calculated in each
      phase. Two patients whose SvO2 values were below 55% during the postoperative
      course needed reoperation for atrioventricular valve regurgitation in one case
      for PV stenosis in the other case. CO increased significantly (p < 0.05) after
      extubation (phase D), compared with that of controlled ventilation (phase B).
      Under hypothermia (phase A), urinary output was relatively higher with lower CO.
      There was a significant correlation between SvO2 and CO (R = 0.61) in phase A,
      however there was no correlation in phase E. Fractional oxygen extraction in
      phase A was significantly lower than in phase B. In conclusion, the continuous
      SvO2 measurements reflected real-time changes in cardiac output in the immediate
      post-Fontan patients. Induced hypothermia was beneficial in increasing urinary
      output presumably through the correction of maldistribution of cardiac output in
      post-Fontant patients. Arousal from anesthesia and spontaneous ventilation seemed
      advantageous for increasing cardiac output, hence, early extubation should be
      encouraged in the management of post-Fontan patients.

PMID- 8753087
TI  - [Efficacy of left atrial only procedure for the treatment of chronic atrial
      fibrillation associated with mitral valve disease].
AB  - We supposed that chronic atrial fibrillation originated as a result of
      discontinuity of the refractory period of the dilated left atrium in the mitral
      valvular disease. We then performed left atrial only procedures to treat the
      chronic atrial fibrillation (AF) associated with mitral valve disease. These
      procedures were the left atrial isolation and the modified left sided maze
      procedure, consisting of isolation of all pulmonary veins and cryoablation to the
      posterior wall of the left atrium, in addition to excision of the left atrial
      appendage. Twenty-eight patients underwent these procedures over the past thirty
      months. Patient ages and the duration of AF ranged from 37 to 71 years and from
      0.5 to 26 years, with an average of 8.3 years, respectively. Chronic AF
      disappeared in twenty-four patients (86%) at discharge. Three patients with
      severe tricuspid insufficiency had sustained AF and one patient had atrial
      flutter postoperatively. Three patients showed sick sinus syndrome
      postoperatively and two of these required a DDD pacemaker. Severe tricuspid
      regurgitation (p < 0.020) was the factor in recurrence of AF. Left atrial only
      procedures were effective in the treatment of chronic AF associated with mitral
      valvular disease.

PMID- 8753088
TI  - [Significance of systemic inflammatory response syndrome at cardiopulmonary
      bypass].
AB  - Systemic Inflammatory Response Syndrome (SIRS) is a new concept of entry criteria
      for sepsis. This concept, when applied to area of Multiple Organ Failure (MOF),
      is considered to be a preparatory state for MOF. To study the significance of
      SIRS state at cardiac surgery, we measured the body temperature, white blood cell
      count, respiratory rate and heart rate of 18 patients who underwent elective
      cardiac surgery, from the 1st post-operative day to the 7th post-operative day.
      We also measured Interleukin-6 and 8 (IL-6 and IL-8) to understand the
      relationship between the SIRS state and inflammatory cytokines just after
      cardiopulmonary bypass (CPB), at the 1st, 3rd and 6th postoperative day. The
      result was as follows: Patients with CPB more than 120 minutes have more
      frequency and longer duration of SIRS than patients with CPB less than 120
      minutes. Serum levels of IL-8 at SIRS state were revealed statistically higher
      than at non-SIRS case. Duration of SIRS state was related to CPB time and serum
      levels of IL-6 and IL-8 just after CPB. We concluded that SIRS state is an
      indication for anti-cytokine therapy to prevent MOF, and it is important to
      shorten CPB time in order to decrease the duration of SIRS.

PMID- 8753089
TI  - [Evaluation of tissue oxygenation utilizing a tonometer in the stomach tube or
      colon used in substitutive esophagus after surgery for esophageal cancer].
AB  - We measured serial changes in mucosal pH (pHi) as an index of blood flow of the
      stomach tube or the colon in a substitutive esophagus using a tonometer in 18
      patients following surgery for esophageal cancer. The pHi showed the lowest level
      at the postoperative 1 hr (PO 1 hr) and increased significantly at PO 6 hr. At PO
      12 hr, pHi showed the level of more than pHi 7.3 which increased significantly
      compared with PO 6 hr. The oxygen delivery and oxygen consumption increased
      significantly from PO 1 hr at PO 6 hr but not changed between 6 and 12 hr. It was
      suggested that the blood flow was inadequate in the stomach tube or the colon as
      a substitutive esophagus within PO 12 hr following operation despite of adequate
      oxygen delivery systemically. In this series, the decreased pHi were shown in 2
      patients with minor leakage of anastomosis and in one patients with the
      perforation of stomach tube. The correlation between pHi and modified respiratory
      index was recognized at PO 12 hr and 24 hr suggesting that pHi was associated
      with the pulmonary dysfunction. Therefore, it was suggested that the value and
      change of pHi is an useful predicting index of occurrence of anastomotic leakage
      or respiratory failure which may be a fatal postoperative complication after
      surgery for esophageal cancer.

PMID- 8753090
TI  - [Coronary artery bypass grafting under bradycardia induced by ultra-short acting
      beta blocker].
AB  - From Dec. 1993 to May, 1994, coronary artery bypass grafting (CABG) was performed
      in 7 patients under bradycardia induced by an ultra-short acting beta blocker
      (esmolol). The ages ranged from 51 to 68 years. There was one patient with low
      ejection fraction (EF = 31%) and two patients with porcelain aorta. A tepid
      temperature was maintained during cardiopulmonary bypass (CPB). A high flow rate
      of 2.2-2.6 liter/min/m2 was applied to control perfusion pressure above 50 mmHg
      during CPB. After CPB was started, a high dose of esomolol was added (10-30 mg/kg
      intravenous bolus followed by a continuous infusion of 1-4 mg/kg/min). Severe
      bradycardia was achieved by the initial loading of esmolol. The mean heart rate
      was significantly (p < 0.01) decreased from 78 +/- 12 bpm to 49 +/- 7 bpm by the
      loading. Altogether, 25 anastomoses (11 ITA, 6 GEA, 8 SVG) were performed to LAD
      (10), Cx (7) and RCA (8), with an average of 3.6 +/- 0.9 anastomoses/patient.
      IABP was required for 2 patients postoperatively. There was no operative death,
      but one hospital death due to aspiration pneumonia 3 months later. Postoperative
      max CPK-MB was low (17.4 +/- 9.7 IU/L) in 6 patients. The postoperative
      angiography was performed in all patients with a patency rate of 88%. It was
      considered that esmolol facilitated CABG under beating heart and this technique
      is suitable for patients with severe atheromatous disease of the ascending aorta
      or patients with a low ejection fraction to avoid aortic cross-clamping.

PMID- 8753091
TI  - [Surgical treatment for subacute left ventricular free wall rupture complicating
      acute myocardial infarction--pericardial patch gluing method].
AB  - We reviewed 22 cases with surgical repair for subacute left ventricular free wall
      rupture complicating acute myocardial infarction. Different operative technique
      was used. Direct closure or patch repair with infarctectomy was preformed in
      first patients with a great difficulty in hemostasis. Since 1988 we sutured a
      large pericardial patch covering the infarcted myocardium under extra corporeal
      circulation in 11 patients (pericardial patch suture technique). From 1993 we
      began to glue a pericardial patch with Aron alpha without cardiopulmonary bypass
      (pericardial patch gluing technique). There were eight early death and four late
      death. Most common cause of death was low cardiac output syndrome (LOS). With
      medical therapy 13 patients in cardiogenic shock improved before surgery and only
      three developed postoperative LOS, but all six patients with sustained shock
      developed LOS without survivor (p = 0.007). Two of the five patients underwent
      direct closure or infarctectomy and seven of the 11 employed pericardial patch
      suture technique developed LOS, but none of the six used pericardial patch gluing
      technique developed LOS. Medical treatment such as intraaortic balloon pumping,
      catecholamine and subxyphoid drainage in order to improve hemodynamic condition
      before surgery is extremely important. Pericardial patch gluing technique seems
      to be useful since cardiac function would be maximally preserved.

PMID- 8753092
TI  - [A case report of transaortic mitral valve replacement in Marfan's syndrome].
AB  - One-stage operation was successfully performed in 30-year-old male with annulo
      aortic ectasia and mitral valve regurgitation secondary to Marfan's syndrome. The
      replacement of the mitral valve was performed through aortic root. The
      transaortic mitral valve replacement employed here should prove useful for
      similar cases requiring reconstruction of aortic root and replacement of mitral
      valve simultaneously in Malfan's syndrome.

PMID- 8753093
TI  - [A case report of mediastinitis due to methicillin resistant Staphylococcus
      aureus after total aortic arch replacement].
AB  - A 78-year-old man underwent total aortic arch replacement for ruptured aortic
      arch aneurysm. Two weeks after the surgery, high fever and leucocytosis
      developed. He was placed on a regimen of antibiotics. However, mediastinitis
      eventually ensued five weeks later with the pus draining from the sternotomy
      wound. The culture revealed a Methicillin resistant staphylococcus aureus. The
      infected tissue was debrided from the mediastinal cavity 40 days postoperatively.
      The cavity was kept open and was intermittently irrigated with 2% Providone
      iodine for three days. Subsequently, an omental graft was placed. The infection
      successfully subsided gradually and the patient has been well for a year and a
      half after the initial surgery. The procedure is considered to be extremely
      effective for the management of a drastic infection involving thoracic aortic
      prosthesis.

PMID- 8753094
TI  - [A case of bronchial neurinoma].
AB  - Neurinoma of the bronchial tree is extremely rare. We report a case of bronchial
      neurinoma involving a 21-year-old woman. The patient was admitted due to an
      abnormal shadow on chest X-ray, with cough and sputum production. Chest CT and
      MRI showed that the tumor arose from the left lower bronchus and
      bronchofiberscopic examination revealed complete obstruction of the lower
      bronchus by a polypoid tumor. A left lower lobectomy was performed based on the
      histological diagnosis of benign neurinoma and the postoperative course was
      uneventful. The tumor was 7.0 x 6.0 x 5.0 cm in size and had grown
      endobronchially without penetrating the bronchial wall. Pathological diagnosis
      was Antoni A type benign neurinoma. Since malignant or metastasized tumors have
      been reported in cases of tracheobronchial or intrapulmonary neurinoma, complete
      surgical resection of bronchial neurinomas should be performed.

PMID- 8753095
TI  - [An aortic valve-sparing operation (David's operation) for a patient with annulo
      aortic ectasia (AAE) and aortic regurgitation (AR)--evaluation by intraoperative
      endoscopy].
AB  - Now, the standard operation for a case with AAE and AR is the composite graft
      replacement. In this case, an aortic valve sparing aortic root reconstruction,
      the so-called David's operation, and the intraoperative endoscopic study were
      performed. In the case of 68-year-old male with AAE and AR, the aortic valve was
      reimplanted in a tubular Dacron graft and coronary arteries were reconstructed
      with the Carrel patch technique. After the completion of the aortic root
      reconstruction, intraoperative endoscopic study revealed the disappearance of AR.
      Postoperative aortography revealed trivial AR and at present, seven months
      postoperatively, this patient have been uneventful. In this paper, we discuss the
      merits and demerits of the David's operation and the effectiveness of
      intraoperative endoscopic study for the aortic valve sparing operation.

PMID- 8753096
TI  - [Thoracic duct cyst--a case report].
AB  - The patient was a 59-year-old man with a 5-month history of cough, difficulty
      breathing, and palpitations while working. Initial examination at the internal
      medicine department of our hospital in August 1992 revealed a mass in the left
      side of the neck, and he was admitted for further examination and treatment.
      Preoperative investigations revealed a cystic lesion extending from the left neck
      area to the mediastinum. The mass was resected on August 13, 1992. Based on the
      intraoperative findings and postoperative histological examination, a diagnosis
      of thoracic duct cyst was made. The postoperative course was good and the patient
      was discharged after two weeks. This is extremely rare case, and the Trap door
      surgical approach proved useful for resection.

PMID- 8753097
TI  - [A case report of surgical treatment for acute mitral insufficiency associated
      with acute gastric lesion].
AB  - A 76-year-old female was admitted to our hospital due to anterior chest pain and
      dyspnea. Mitral regurgitation due to prolapse of the posterior leaflet was
      detected by UCG. After admission, massive gastric hemorrhage was observed.
      Because hemostatic therapy using endoscopy was not effective, partial gastrectomy
      was performed. The origin of the hemorrhage, an acute gastric ulcer, was located
      on the side of the minor curvature of the corpus ventriculi. After gastrectomy,
      the patient underwent medical treatment using an IABP, but the left heart failure
      was not reduced, and the pulmonary edema worsened. At 18 hours after gastrectomy,
      MVR was performed. The cause of regurgitation is torn chordae of the posterior
      leaflet. The postoperative course was good, and the patient is doing well in NYHA
      class 1. This case is the first report of acute mitral insufficiency associated
      with acute gastric lesion in Japan.

PMID- 8753098
TI  - [Simultaneous aortic root and total arch graft replacement in a patient with
      aortitis syndrome].
AB  - The patient was a 45-year-old female diagnosed with aortitis syndrome and aortic
      regurgitation (AR). She had been taking steroid therapy since 1975. She had
      recently developed congestive heart failure due to AR while both the ascending
      aorta and aortic arch were enlarged. She had no inflammatory reaction on
      admission. An aortogram showed heavy dilation of both the ascending aorta and
      aortic arch and maximum diameters was 11 cm in the ascending aorta and 4.5 cm in
      the descending aorta. There was an obstruction of the left subclavian artery.
      Moderate AR was seen on an echocardiogram. She had a simultaneous graft
      replacement of aortic root and total arch. The aortic root was replaced with
      composite graft and coronary arteries were implanted using Carrel's patch
      technique, and the aortic arch was also replaced with a graft with two side
      branches. The postoperative course was uneventful without complication of
      cerebral infarction or paraplegia. The postoperative aortogram showed stenosis of
      the left carotid artery, but no abnormality of the coronary orifices and graft
      anastomosis. She returned home with disappearance of symptoms of congestive heart
      failure.

PMID- 8753099
TI  - [Re-operation for Budd-Chiari syndrome].
AB  - A 42-year-old man, who underwent a radical operation for Budd-Chiari syndrome
      under femoro-femoral bypass in our hospital 5 years ago, was re-admitted for
      evaluation of progressive liver dysfunction and dilatation of superficial veins
      of scrotum and lower extremities. Cavography revealed complete obstruction at the
      portion of previous patch dilatation. We performed re-do operation by the same
      method except we chose this time the heparin-coated circulatory system including
      centrifugal pump and ringed ePTFE graft as a material of patch dilatation.
      Cavography after the re-do operation revealed widely patent IVC-RA junction and
      he has been doing well.

PMID- 8753101
TI  - [Open heart surgery in patients with chronic dialysis].
AB  - From January, 1986 to May, 1995, twelve patients with dialysis (11 hemodialysis;
      HD, and one continuous ambulatory peritoneal dialysis; CAPD) received open heart
      surgery. They consist of 10 males and two females aged between 35 and 66 with a
      mean of 58.8. The duration of dialysis was 6.8 years in a mean (the shortest for
      2 months and the longest for 16 years). They classified into an equal number of
      four in NYHA class II, III and IV. Two of them had isolated coronary artery
      bypass grafting, four had aortic valve replacement (AVR) and two had mitral valve
      replacement (MVR). Others were each one of AVR and MVR, AVR plus MVR with
      tricuspid annuloplasty (TAP), AVR plus TAP, and removal of left atrial myxoma.
      All patients except for one of CAPD were dialysed daily 2 or 3 days before
      operation. Three patients were managed postoperatively with HD, one with PD, six
      with continuous hemodiafiltration, and two with continuous hemofiltration. The
      operative mortality was 25% (3/12). The causes of death were left ventricular
      rupture, bronchospasm, and respiratory failure. All patients who died were in
      class in III and IV. For the improvement of the results we emphasize the
      necessity of early operation that should be scheduled in class II period.

PMID- 8753100
TI  - [Acute type A aortic dissection after replacement of descending thoracic aorta
      for type B aortic dissection].
AB  - Two cases of acute type A aortic dissection after replacement of descending
      thoracic aorta for type B dissection were reported. One case involved a 75-year
      old male who had hypertension. The second case involved a 33-year-old female with
      a familial history of thoracic aneurysms. Both patients underwent simultaneous
      graft replacement of the ascending aorta and total aortic arch using selective
      perfusion to the brain. Both patients survived the operations, and the
      postoperative courses were satisfactory. Acute type A dissection after
      replacement of descending thoracic aorta for type B dissection is rare, and
      careful and long-term follow-up is needed for the patients.

PMID- 8753102
TI  - [A case of the giant and pedunculated thrombus formation in the left atrium with
      normal mitral valve].
AB  - Occurrence of thrombus formation in the left atrium is rare without accompanying
      abnormalities at the mitral valve. Only a few cases of giant and pedunculated
      thromboses in the left atrium have been reported in the Japanese literatures.
      This is a case report of giant thrombus in the left atrium treated surgically.
      Patient was 61 years old male suffering from palpitation. Physical examination of
      the heart revealed increased first sound and diastolic rumbling at the apex. ECG
      revealed atrial fibrillation and LVH. Echocardiography and chest CT demonstrated
      a huge tumor like mass in the left atrium attached to the septal area. There were
      no abnormalities found at mitral valvular structures or motion. Catheterization
      studies revealed no disturbance of valvular functions. Angiographic examination
      demonstrated smooth surfaced tumor mass occupied left atrium. Coronary
      angiography revealed significant stenosis in segments 6, 7, 9, 12 and 14. Prior
      to surgery, patient was diagnosed myxoma of the left atrium and ischemic heart
      disease. Removal of the mass and CABG were carried out at a same time. Pathology
      revealed giant and pedunculated globular thrombus. Contributional factors
      possibly growing of such huge thrombus formation explained resulting from atrial
      fibrillation and decreased contractile force of the hypertrophied ventricle.

PMID- 8753103
TI  - [Malignant mediastinal schwannoma associated with von Recklinghausen's disease--a
      resected case].
AB  - A case of malignant mediastinal schwannoma associated with von Recklinghausen's
      disease is reported. A 44-year-old woman was admitted to Chiba University
      Hospital because of an abnormal shadow on chest X-ray film. CT scan showed a
      cystic tumor in upper mediastinum and then tumor extirpation was performed. This
      cystic tumor was related to the sympathetic trunk and 60 x 35 x 33 mm in
      diameter. Its cut surface showed a thick irregular capsule and multilocular.
      Microscopic examination disclosed malignant cells with mitosis associated with
      neurofibroma. An immunohistochemical staining of these malignant cells with anti
      S-100 protein showed positive reaction. From these findings this tumor was
      diagnosed as malignant schwannoma. There is no evidence of recurrence two year
      after the operation. This is the first case of malignant schwannoma with cystic
      formation in Japan.

PMID- 8753104
TI  - [A case of tricuspid and mitral valve replacement for incomplete endocardial
      cushion defect].
AB  - A 56-year-old female who was diagnosed incomplete endocardial cushion defect,
      underwent closure of ostium primum defect and repair of mitral cleft 2 years ago.
      Mitral and tricuspid ring annuloplasty was done 9 months after the first
      operation because of an increment of mitral and tricuspid valve regurgitation.
      The Third operation, mitral valve replacement by mechanical valve and tricuspid
      valve replacement by bioprosthetic valve, was performed because of the gradually
      increased mitral stenosis and tricuspid regurgitation. Post-operative course was
      uneventful. Resected anterior cusp of mitral and tricuspid valve revealed
      hypertrophy and shortness macroscopically, and revealed fibrosis and
      calcification histopathologically. It was considered that remarkable
      regurgitation was due to secondary change of both valves. We concluded that valve
      replacement should be performed for case of secondary change of atrioventricular
      valve in adult patient.

PMID- 8753105
TI  - [Papillary muscle rupture complicating acute myocardial infarction--treatment
      with mitral valve replacement and coronary bypass surgery in acute phase].
AB  - Complete rupture of a papillary muscle following acute myocardial infarction is a
      severe complication that is typically associated with acute left ventricular
      failure, pulmonary edema, and relentless clinical deterioration. The reported
      mortality rates without surgical intervention is almost 90%, therefore, prompt
      operation without prolonged attempts at medical stabilization is the key to
      decrease operative mortality. Although the complete coronary revascularization in
      conjunction with mitral valve replacement is advocated in the western medical
      academic society, there is only a few case of conjunct surgery has been reported
      in Japan. Three successful cases of conjunct surgery of mitral valve replacement
      and coronary complete revascularization in acute phase within one week from the
      onset of acute myocardial infarction (AMI) are described. There were one male and
      two female patients with an average age of 60-year-old (range 48-67), who
      developed cardiogenic shock and admitted to our hospital. The average interval
      between onset of AMI and the appearance of mitral regurgitation (MR) was 38
      hours, and that of the appearance of MR and admission was 40 hours. Surgeries
      were performed within 26 hours (average 13 hours) after admission. The mitral
      valve was replaced with a mechanical valve (St. Jude Medical Valve) and a
      complete coronary revasculatization was done using saphenous vein graft. The
      average period of operation time and aortic cross clamping time were 6 hours 22
      minutes and 109 minutes respectively. The average number of coronary grafting was
      2.3 (range 1-3). Postoperative recovery from cardiogenic shock was uneventful in
      all three patients. The average periods of ICU stay and hospital stay were 5 days
      and 43 days respectively. All patients have regained their social activities with
      mean follow up period of 52 months. Since ischemic heart disease remains the
      leading cause of death in such patients, it is suggested that complete coronary
      revascularization should be performed immediately in conjunction with valve
      replacement even in the acute phase after onset of AMI.

PMID- 8753106
TI  - [Relationship between diaphragm weight and body composition].
AB  - To study the relationship between diaphragm weight and body composition, we
      measured fat body mass and lean body mass by dual-energy X-ray absorptiometry (XR
      26, Norland), and weighed the diaphragms of patients at autopsy. The subjects
      were 22 patients with various diseases (13 men and 9 women, aged 72.6 +/- 9.5
      years). In 8 of the patients, respiratory muscle strength was assessed with
      maximal pressure at the mouth. The diaphragm weight was 185.2 +/- 58.2 g and it
      correlated significantly with lean body mass (r = 0.77, r = 0.73, p < 0.01).
      Maximal inspiratory pressure at TLC correlated significantly with diaphragm
      weight. These results show that respiratory muscle strength is related to
      diaphragm weight and that analysis of body composition may be useful in assessing
      changes in the mass of the diaphragm.

PMID- 8753107
TI  - [Effect of time in culture on modulation of Na(+)-K(+)-ATPase activity in rat
      alveolar type II cells].
AB  - To determine the effect of time in culture on epithelial cell function, we
      evaluated the modulation of Na(+)-K(+)-ATPase activity in rat alveolar type II
      cells in culture. Ouabain sensitivity testing revealed that the alpha-1
      predominance in the enzyme's isoforms was maintained over the 120 hours in
      culture. Basal Na(+)-K(+)-ATPase activity in the whole cell homogenate did not
      differ significantly between cells cultured for 48 hours and those cultured for
      120 hours. Terbutaline (10 mM) did not activate Na(+)-K(+)-ATPase in the cells
      cultured for 48 hours, but, it significantly increased the activity of this
      enzyme in the cells cultured for 120 hours cells cultured for 48 hours, produced
      intracellular cyclic AMP after exposure to 10 mM of terbutaline. These results
      indicate that the coupling between Na(+)-K(+)-ATPase and the beta-adrenergic
      pathway in alveolar type II cells can be influenced by the time in cell culture.

PMID- 8753108
TI  - [Comparison between high-resolution computed tomography and 99mTc-technegas SPECT
      pulmonary emphysema].
AB  - Scintigraphy with 99mTc-technegas was recently introduced for clinical imaging of
      lung ventilation. This method has been found to be useful in emergencies, to be
      more suitable for single photon emission computed tomography (SPECT) than other
      agents used in ventilation scintigraphy, and could reveal abnormalities in
      ventilation more easily than high resolusion computed tomography (HRCT) in
      pulmonary emphysema. We compared 99mTc-technegas SPECT with HRCT in six regions:
      the right upper, middle, and lower lobes, the left upper lobe, the lingula, and
      the left lower lobe, in 15 patients with pulmonary emphysema. Patients with
      centrilobular emphysema tended to show stronger changes in upper lobes than in
      lower lobes on both 99mTc-technegas SPECT and HRCT. Some regions showed no change
      on HRCT but various changes on 99mTc-SPECT. Patients with panlobular emphysema
      showed severe changes on 99mTc-SPECT in lower lung fields in which well
      demarcated areas of low attenuation were not seen on HRCT. We conclude that 99mTc
      SPECT is useful for detecting early changes and panlobular changes in pulmonary
      emphysema.

PMID- 8753110
TI  - [Subsets of lymphocytes in bronchoalveolar-lavage fluid from patients with
      idiopathic bronchiolitis obliterans organizing pneumonia].
AB  - Lymphocyte activation may be involved in interstitial inflammatory processes in
      the lungs. We analyzed lymphocytes in bronchoalveolar lavage fluid obtained from
      5 patients with idiopathic bronchiolitis obliterans organizing pneumonia and from
      7 control subjects. Lymphocytes were analyzed by two-flow cytometry. Differential
      cell counts showed that the percentage and the number of lymphocytes was higher
      in the patients (32.9 +/- 21.9%, 12.8 +/- 8.32 x 10(4) cells/ml) than in the
      controls (8.31 +/- 3.66%, 0.69 +/- 0.39 x 10(4) cells/ml, p < 0.05). In
      particular, the patients had many more CD8+ S6F1+ lymphocytes (which are
      considered to be activated cytotoxic T lymphocytes; 32.2 +/- 11.8%, 42.0 +/- 26.5
      x 10(3) cells/ml) than did the controls (6.31 +/- 1.69%, 0.42 +/- 0.25 x 10(3)
      cells/ml, p < 0.01). These data indicate that activated cytotoxic T lymphocytes
      may be important in the pathogenesis of bronchiolitis obliterans organizing
      preumonia.

PMID- 8753109
TI  - [Effect of timing of granulocyte-colony stimulating factor administration on
      leukopenia induced by systemic chemotherapy in patients with non-small-cell lung
      cancer--multi-center randomized crossover study].
AB  - Sixty-six chemotherapy-naive patients with non-small-cell carcinoma of the lung
      were given two courses of systemic chemotherapy consisting of mitomycin C,
      vindesine, and cisplatin. The effect of the timing of administration of
      grannulocyte colony-stimulating factor (G-CSF) on the incidence of neutropenic
      fever, the nadir leukocyte count, the duration of neutropenia ( < or = 1000/mm3),
      and the time needed for recovery from neutropenia was studied. Patients were
      assigned at random to begin receiving G-CSF (50 microns/m2, subcutaneously)
      either when the leukocyte count was less than or equal to 1000/mm3 (group I) or
      when it was between 1000/mm3 and 2000/mm3 (group II), in a crossover fashion. The
      nadir leukocyte count was lower in group I than in group II (859/mm3 and
      1215/mm3, respectively). The duration of leukopenia (defined as a leukocyte count
      less than or equal to 1000/mm3) was greater in group I than in group II (1.5 days
      and 0.8 day, respectively), as was the time needed for recovery to a leukocyte
      count of 2000/mm3 (1.9 days and 1.6 days, respectively) (p < 0.05). No
      differences were found in the incidence of neutropenic fever (group I: 44%, group
      Ii: 45%), in the duration of fever (group I: 2.3 days, group II: 2.8 days), or in
      the duration of G-CSF use (group I: 6.3 days, group II: 6.8 days). There were no
      treatment-related deaths in either group. We conclude that when this type of
      combination chemotherapy is given for non-small-cell carcinoma of the lung,
      administration of G-CSF can be postponed without clinical problems until the
      leukocyte count is less than of equal to 1000/mm3.

PMID- 8753111
TI  - [High-dose inhaled beclomethasone in long-term management of chronic severe
      asthma--usefulness and dose-dependence].
AB  - We studied the usefulness of 18 weeks of therapy with two high doses of inhaled
      beclomethasone dipropionate (BDP) in the management of severe asthma in adults.
      The patients had asthma symptoms that had not been controlled by combination
      therapy with BDP (800 micrograms/day) and bronchodilators. They were divided into
      two groups. Patients in group A (n = 16) were treated with 1800 micrograms/day of
      BDP and bronchodilators. Patients in group B (n = 10) were treated with 1400
      micrograms/day of BDP and bronchodilators. BDP was inhaled via a large spacer
      (Volumatic). Eleven patients in group A and 6 patients in group B had been given
      an oral steroid regularly before the study. Asthma symptom scores, peak
      expiratory flow (PEF), pulmonary function, bronchial reactivity to methacholine,
      the total amount of oral steroid, and adrenocortical function were recorded.
      Results. 1) Clinical characteristics before the start of the study did not differ
      between groups. 2) Asthma symptom scores decreased to a greater extent in
      patients who received the higher dose of BDP than in those who received the lower
      dose. 3) Only the higher dose of BDP significantly increased evening and morning
      % PEF, as measured 6 weeks and 8 weeks after the start of the treatment. 4) Only
      the higher dose of BDP significantly increased the FEV1 and the PC20 for
      methacholine. FVC did not increase. 5) Only the higher dose of BDP significantly
      decreased the total amount of oral steroid needed to control asthma. 6) Results
      of the rapid ACTH test indicated that neither dose of BDP suppressed
      adrenocoritical function. Furthermore, the serum cortisol level measured early in
      the morning increased to within the normal range in the three patients in whom
      oral steroid therapy could be reduced or stopped after treatment. These data
      indicate that 1800 micrograms of BDP per day is more effective than 1400
      micrograms/day at the beginning of long-term management of severe chronic asthma
      in adults whose symptoms are not controlled with the combination of 800
      micrograms/day BDP and bronchodilators. Therapy with a higher dose (at least 1600
      micrograms/day) of an inhaled steroid is more useful and should be promptly begun
      to treat severe asthma.

PMID- 8753112
TI  - [Hypertonic saline induced bronchoconstriction in sensitized rabbits].
AB  - Hypertonic saline is a potent stimulus to airway narrowing in most asthmatic
      patients. However, the mechanism of airway narrowing induced by a change in
      osmolarity is not clearly understood. In ovalbumin-sensitized rabbits, we found
      that bronchoconstriction occurred after inhalation of hypertonic saline, and then
      studied the mechanisms responsible for this bronchoconstriction. Eighteen
      anesthetized, paralyzed, mechanically ventilated (40 breath/min, TV 7 ml/kg)
      ovalbumin-sensitized rabbits were exposed to aerosols of hypertonic saline
      (ultrasonic nebulizer, 0.5 ml/min, 1 min). Total lung resistance (RL) and dynamic
      compliance (Cdyr) of the lung were measured before and after the exposure. The
      concentration of NaCl was increased from 0.9% to 7.2% in 0.9% steps. RL increased
      and Cdyr decreased as the dose of NaCl rose and they reached plateaus at doses of
      6.3% and 7.2%, respectively. These responses were markedly inhibited by treatment
      with atropine (5 mg/kg i.v., p < 0.05 vs. control group), but treatment with
      chlorpheniramine (1 mg/kg iv.) suppressed the responses only at low
      concentrations of NaCl. In contrast, treatment with indomethacin, did not
      significantly change the responses. We conclude that inhalation of hypertonic
      saline can cause bronchoconstriction in sensitized rabbits, and that vagal
      stimulation plays a major role in this bronchoconstriction.

PMID- 8753114
TI  - [Lymphangiomyomatosis with chylous ascites treatment successfully by peritoneo
      venous shunting].
AB  - A 49-year-old woman was admitted to our hospital because of coughing and dyspnea.
      A chest roentogenogram showed emphysematous changes and a diffuse reticular
      shadow. A high-resolution CT scan of the chest showed many small cysts throughout
      the lungs. Lymphangiomyomatosis was diagnosed after examination of a specimen
      obtained by transbronchial biopsy. Abdominal distention due to chylous ascites
      developed during the hospital stay despite anti-estrogen therapy. Because the
      ascites was resistant to conservative therapy, we decided to begin peritoneo
      venous shunting with a Denver Shunt system. After the operation, the abdominal
      distention was controlled for 1 year and 11 months, at which time the patient
      died of respiratory and heart failure with pneumonia. At autopsy, the shunt was
      patent and functional although about 900 ml of serous ascites fluid was present.
      An adenocarcinoma was found in the upper lobe of the right lung, but it may not
      have been related to the lymphangiomyomatosis. Peritoneovenous shunting with a
      Denver Shunt can be used to treat chylous ascites due to lymphangiomyomatosis
      when conservative therapy is insufficient.

PMID- 8753113
TI  - [High concentrations of interleukin-8 in bronchoalveolar lavage fluid from a
      patient with adult respiratory distress syndrome].
AB  - A 75-year-old man was admitted to the hospital due to acute onset of a dry cough
      and dyspnea on exertion. Arterial blood gas analysis showed hypoxemia (PaO2 = 63
      Torr) on room air. Chest radiography and computed tomography showed diffuse
      bilateral infiltrates. Adult respiratory distress syndrome was diagnosed from the
      findings described above and from the lack of evidence of left heart failure.
      Diffuse alveolar damage was confirmed at autopsy. During the course of his
      illness, the patient underwent bronchoalveolar lavage five times. The recovered
      fluid had high concentrations of interleukin-8 (IL-8), with a maximum of 6260
      pg/ml and a minimum of 190 pg/ml, and these values correlated with the number of
      polymorphonuclear cells in the fluid. Levels of leukotriene B4, another
      chemotactic factor for PMN, in the lavage fluid were not high. We conclude that
      IL-8 was a major chemoattractant for PMN in the alveoli of this patient.

PMID- 8753115
TI  - [Swyer-James syndrome with unilateral pulmonary edema].
AB  - A 64-year-old man with ischemic heart disease was admitted to our hospital
      because of dyspnea. A chest X-ray film showed a butterfly shadow in the right
      lung. A chest X-ray film obtained before the patient had respiratory symptoms
      showed hyperlucency of the left lung. CT scans obtained at maximal inspiration
      and expiration revealed air trapping. Pulmonary arteriography showed that the
      left pulmonary artery and its branches were very small. Cardiac catheterization
      showed poor cardiac function. Swyer-James syndrome should be included in the
      differential diagnosis of patients with unilateral pulmonary edema.

PMID- 8753116
TI  - [Pulmonary arterio-venous fistula treated by embolization with steel coils].
AB  - A 63-year-old man was referred to our hospital for evaluation and treatment of
      severe dyspnea on exertion which had persisted for a few years. He presented with
      cyanosis and markedly clubbed fingers, and laboratory data disclosed hypoxemia,
      polycythemia, and liver dysfunction. A chest X-ray film showed increased vascular
      markings in both lower lung fields. Arterial blood gas analysis showed severe
      hypoxemia, with a PaO2 of 46 Torr and a PaCO2 of 31 Torr while the patient was
      breathing room air. The PaO2 increased only slightly with inhalation of 100%
      oxygen, which suggested the presence of a large R-L shunt. The hepatopulmonary
      syndrome was diagnosed. Angiography of the pulmonary artery revealed a large
      pulmonary arterio-venous fistula with markedly dilated arteries in both lower
      lobes. Transarterial embolization was done three times with a total of 62 metal
      coils. There were no complications. Embolization reduced the shunt from 56% to
      31%, increased the PaO2, and relieved the dyspnea. Pulmonary artery embolization
      can be useful in treating pulmonary arterio-venous fistulas associated with the
      hepatopulmonary syndrome.

PMID- 8753117
TI  - [Primary pulmonary cryptococcosis treated by thoracoscopic resection].
AB  - A 37-year-old man was admitted to the hospital because of an abnormal shadow in
      the right lower field on a chest roentgenogram. The lesion was calcified and was
      therefore suspected to be benign. Thoracoscopic resention was performed. The
      pathological diagnosis was cryptococcosis of the lung. The lesion was completely
      resected, so no antifungal drug was given. The patient was doing well as of 12
      months after the operation.

PMID- 8753118
TI  - [Malignant lymphoma of the chest wall in a patient with chronic empyema].
AB  - A 76-year-old man presented with the chief complaints of appetite loss and
      general fatigue. He was admitted with the initial diagnosis of empyema
      necessitatis, and right thoracic drainage was performed. Nevertheless, the
      subcutaneous mass in the right side of the chest wall did not shrink, and
      examination of a specimen obtained by percutaneous needle biopsy resulted in the
      diagnosis of non-Hodgkin's lymphoma, intermediate lymphocytic type. The patient
      was treated with Adriamycin, vincristine, prednisolone, and cyclophosphamide, but
      died of pneumonia and cachexia five months after symptoms first appeared. The
      diagnosis of intermediate lymphocytic lymphoma, B cell type was made at autopsy.
      Only 53 cases of malignant lymphoma associated with chronic empyema have been
      reported in Japan. Surgery was often not done because of the patient's advanced
      age or poor pulmonary function; diagnosis was often difficult. However, review of
      the 53 reported cases suggested that resection of the tumor, if possible, would
      improve the prognosis. Malignant lymphoma should be considered when there is
      chronic empyema, because such cases are now being reported more frequently.

PMID- 8753119
TI  - [Recurrence of the acute respiratory distress syndrome in a patient with liver
      cirrhosis and diabetes mellitus].
AB  - The acute respiratory distress syndrome developed twice within 4 months in a
      patient with liver cirrhosis and diabetes mellitus. The diagnosis was made from
      the diffuse alveolar shadows seen on a chest X-ray film and a lung injury score
      of 3.3. The initial episode resolved quickly with steroid pulse therapy. The
      second episode resolved to some extent after the same therapy, but the patient
      died of hepatic and renal failure followed by acute pneumonia. The causes of the
      first and second episodes were considered to be different and the outcome
      depended on liver and kidney function. We report this case because the acute
      respiratory distress syndrome rarely occurs within 4 months.

PMID- 8753121
TI  - [Chest wall Castleman's disease with massive pleural effusion].
AB  - A 38-year-old woman was admitted to our hospital due to dyspnea. A chest X-ray
      film showed a right-sided chest wall tumor and a massive pleural effusion. A
      sharply defined round tumor, 5 cm in diameter, was seen on a chest CT scan; this
      tumor was strongly stained by contrast medium. Angiography showed a feeding
      artery and strong tumor staining. Gallium scintigraphy showed no accumulation.
      The tumor was resected, after which the retention of pleural fluid stopped. The
      pathological diagnosis was hyaline vascular type Castleman's disease. In this
      case, hyaline vascular type Castleman's disease manifested on the chest wall as a
      vessel-rich tumor; can cause retention of pleural fluid without the syndrome of
      polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes.

PMID- 8753120
TI  - [Primary Non-Hodgkin's lymphoma in the chest wall without preceding disease].
AB  - An 80-year-old man was admitted to our hospital with complaints of left-sided
      chest pain and swelling. A chest roentgenogram revealed a left chest-wall mass.
      Examination of a biopsy specimen of the mass led to the diagnosis of Non
      Hodgkin's lymphoma of diffuse mixed-cell type. Immunohistological examination
      revealed that it was B-cell type. The chest-wall mass was markedly smaller after
      radiation therapy, and the patient had a complete remission. About 1 year and 10
      months later, Non-Hodgkin's lymphoma developed in the right femur. Combination
      chemotherapy (cyclophosphamide, adriamycin, vincristine, and prednisolone) and
      radiation therapy were given. The patient went into a complete remission, and is
      alive at the time of this writing, 2 years and 6 months after he was first
      treated. Almost all malignant lymphomas of the chest wall arise in cases of
      chronic tuberculous pyothorax or tuberculous pleuritis, but in this case there
      was no preceding disease. When the chest roentgenogram shows a chest-wall mass,
      we must consider the possibility of malignant lymphoma, even if there is no
      preceding disease.

PMID- 8753122
TI  - [Amyloidosis secondary to bronchiectasis].
AB  - A 77-year-old woman was hospitalized repeatly due to frequent hemoptysis and
      production of bloodly sputum for several years. Bronchography in 1989 revealed
      bronchiectasis. She had complained of abdominal pain and diarrhea since 1991, and
      her urine was first positive for protein in 1992. She was admitted to our
      hospital in October 1992 because of edema, anemia, and hypoproteinemia. Despite
      treatment, renal dysfunction and the gastrointestinal disorder progressed and she
      died in January 1993. An autopsy revealed diffuse depositions of amyloid in many
      organs, especially in the kidney and the gastrointestinal tract. This amyloid
      protein was identified as AA protein, which was suggestive of secondary
      amyloidosis. Bronchiectasis appears to have been the disease underlying this
      patient's amyloidosis.

PMID- 8753123
TI  - [Rigid spine syndrome associated with marked hypoxemia and hypercapnia].
AB  - A 48-year-old man was referred to our hospital because of hypoxemia (PaO2 = 43
      mmHg), hypercapnia (PaCO2 = 70 mmHg), complete atrio-ventricular block, and heart
      failure. He also had limitation of spine flexion, scoliosis, deformity of the rib
      cage, and constriction of the ankle joints, complicated by cor pulmonale. These
      findings were compatible with rigid spine syndrome. To avoid progressive
      pulmonary hypertension and hypoxemia, nasal BiPAP and home oxygen therapy (0.5
      liters/minute) were begun. Rigid spine syndrome is clinically characterized by
      limitation of spine flexion, and the limitation of thoracic movement often causes
      severe constrictive respiratory dysfunction. This syndrome should be considered
      when evaluating patients who have both thoracic deformity, especially scoliosis,
      and respiratory failure.

PMID- 8753124
TI  - [Pneumonia caused by varicella-zoster virus in a patient with rheumatoid
      arthritis].
AB  - A 56-year-old woman suffering from rheumatoid arthritis, was admitted to our
      hospital for evaluation of fever and dyspnea. A month before admission, she had
      been given a diagnosis of herpes zoster and was treated with an antiviral agent.
      However, a perineal eruption persisted. A chest X-ray film and a chest CT scan
      showed many diffuse nodular shadows in both lung fields. With conservative
      treatment, the shadows regressed along with the skin eruption and other symptoms.
      Pneumonia caused by varicella-zoster virus was diagnosed from the clinical
      course, chest roentgenographic and CT scan findings, and serological data. The
      risk of mortality in varicella-zoster pneumonia is high in adults, especially in
      immunosuppressed patients. Early diagnosis and effective treatment are,
      therefore, essential in the management of this disease. Though varicella-zoster
      pneumonia is rare, chest roentgenographic and CT scan findings are characteristic
      and suggestive. This case may serve as a reminder of the features of varicella
      zoster pneumonia: many nodular shadows on the chest X-ray film and CT scan.

PMID- 8753125
TI  - [Pulmonary sarcoidosis presenting with many cotton-like unilateral shadows].
AB  - A 22-year-old woman came to our hospital for a thorough examination of nodular
      lesions fund in the right lung field on a chest roentgenogram. A CT scan revealed
      typical cotton-like infiltrates: fluffy margins and granular interiors. Pulmonary
      sarcoidosis was diagnosed from examination of biopsy specimens from the lesions.
      The lesions disappeared in 6 months without therapy. Pulmonary sarcoidosis
      presenting only with many cotton-like unilateral shadows is rare. A cotton-like
      infiltrate seen on a CT scan is a valuable finding for the diagnosis of pulmonary
      sarcoidosis.

PMID- 8753126
TI  - [The blink reflex in severely handicapped patients with dysphagia].
AB  - We investigated the blink reflex in 27 severely handicapped patients. 15 males
      and 12 females, from 5 to 60 years old. They were divided into three groups; the
      tube-feeding group (9 patients), the oral-feeding group (9 patients), and the
      mixed-feeding group (9 patients). Seven normal subjects also were included in
      this study. There was a significant difference in the late ipsilateral component
      (R2) between the tube-feeding and oral-feeding groups. The average R 2 time were
      43.0 msec. in the tube-feeding group and 36.7 msec. in the oral feeding group.
      The auditory brainstem response (ABR) showed no significant difference between
      the two groups. These results suggested that the swallowing function in the
      patients needed for tube feeding was affected by not only the cortical lesions
      but also the brainstem ones. Furthermore, it is speculated that the degree of
      brainstem dysfunction in the tube-feeding group was more severe than in the non
      tube-feeding group. The blink reflex is one of the useful electrophysiological
      parameters for evaluating the brainstem function in severely handicapped patients
      with dysphagia.

PMID- 8753127
TI  - [Cerebrospinal fluid neopterin levels in children with neurologic diseases].
AB  - Neopterin has been determined in blood as a marker of cellular immune system
      activation. We studied cerebrospinal fluid (CSF) neopterin levels in children
      with neurologic diseases, and the following results were obtained: (1) CSF
      neopterin levels markedly increased at the acute phase of bacterial meningitis,
      aseptic meningitis, and encephalitis as compared with those in patients without
      neurologic diseased. (2) In the CSF of patients with bacterial meningitis and
      aseptic meningitis, neopterin levels decreased more rapidly than the total cell
      count and 2'5' oligoadenylate synthetase (2-5 AS) did. (3) CSF neopterin in
      patients with non-infectious neurologic diseases was almost equal to that in
      patients without neurologic diseases. (4) There was no correlation between CSF
      neopterin and other CSF values, such as total cell count, mononuclear cell count,
      protein, and 2-5 AS. These results suggest that CSF neopterin is a useful marker
      of inflammatory central nervous diseases.

PMID- 8753128
TI  - [Cognitive function and MRI findings in very low birth weight infants].
AB  - Twenty-two very low birth weight infants at preschool ages of 5-6 years were
      studied to clarify the correlation between cognitive function and MRI findings.
      Cognitive function was evaluated by the Wechsler Intelligence Scale for Children
      Revised (WISC-R) and the Frostig developmental test of visual perception.
      Ventricular enlargement, assessed by the bioccipital index (B. I.) measured on
      MRI, was correlated to cognitive disorders. Children with periventricular high
      intensity areas (T2-weighted images) extending from the posterior periventricular
      region to the parietal lobe tend to highly suffer from cerebral palsy and visuo
      perceptual impairment. These results indicate that the disorders of cognitive
      function in very low birth weight infants were caused by a damage of association
      fibers in periventricular areas which was detectable by MRI.

PMID- 8753129
TI  - [Landau-Kleffner syndrome: relationship between aphasia and
      electroencepharographic changes].
AB  - The relationship between aphasia and electroencephalogram (EEG) findings was
      studied in 2 patients with Landau-Kleffner syndrome. The appearance of diffuse
      spike and wave complexes almost always preceded the exacerbation of aphasia.
      Prior to the improvement of aphasia, EEG abnormality localized into the temporal
      region, and subsequently disappeared.

PMID- 8753131
TI  - [A case of Aicardi syndrome: neurophysiological investigation].
AB  - A Japanese girl developed tonic spasms in series at two months after birth. When
      she was admitted at 4 months, she had generalized muscle hypotonia and could not
      control her head. She had atotal agenesis of the corpus callosum on MRI, reticulo
      lacunitis revealed by ophthalmologic examination, and hypsarrhythmia in EEG.
      Brain stem auditory evoked potentials and flash-visual evoked potentials
      exhibited abnormally asymmetrical findings. The cortical components of
      somatosensory evoked potentials were not elicited on admission, but some
      components became to be recognized on median nerve stimulation in accordance with
      improvement of EEG findings after various therapeutic trials. We concluded that
      these neurophysiological examinations were useful to investigate the abnormal
      lesions of the central nervous system in patients with Aicardi syndrome.

PMID- 8753130
TI  - [Hand-mouth coordination in the low-risk preterm infants in preterm period].
AB  - The spontaneous motor activity of 20 low-risk preterm babies was filmed and their
      arm and hand movements were subjected to a comparative analysis of the
      interrelation between hand, head, eye and mouth movements. This analysis revealed
      that preterm babies can move the hand to mouth directly and the mouth and eye
      were open in 'anticipation' of arrival of the hand. This movement was associated
      with ipsilateral head orientation. This little-known coordination may have an
      important implication for the theory of intersensorimotor relation and for the
      origin of intentionality.

PMID- 8753132
TI  - [A successful treatment with a continuous intravenous lidocaine for a cluster of
      minor seizures in a patient with Doose syndrome].
AB  - We reported a 7-year-old girl with myoclonic-astatic epilepsy of early childhood
      (Doose syndrome). She had minor seizures (i. e. absence, atonic and myoclonic
      seizures) refractory to treatment with many kinds of anti-epileptic drugs as well
      as thyrotropin releasing hormone. Though she had suffered from long-lasting
      clusters of minor seizures, the treatment with continuous intravenous lidocaine
      successfully brought a case of prolonged remission of both clinical seizures and
      EEG abnormalities. It has been reported that lidocaine is effective mainly for
      partial seizures. The efficacy of lidocaine for generalize seizures, however, has
      been reported only in a few papers. We considered that the treatment with
      continuous intravenous lidocaine is indicated in patients with Doose syndrome
      presenting with a cluster of refractory minor seizures.

PMID- 8753133
TI  - [Werdnig-Hoffmann disease type I with progressive ophthalmoplegia and ptosis].
AB  - Although pathological changes are observed in both the oculomotor nucleus and
      abducens nucleus in autopsied cases of infantile progressive spinal muscular
      atrophy, external and internal ocular palsy and ptosis have not been previously
      reported clinically. We presented here two long-surviving cases on respirators
      which gradually developed ophthalmoplegia and ptosis were presented. From our
      observation of these cases, it was suggested that there are certain periods of
      latencies between the occurrence of pathological changes and their clinical
      manifestation and that the lack of clinical signs of upper cranial nerve
      involvement in cases with Werdnig-Hoffmann type I is due to their short survival
      length.

PMID- 8753134
TI  - [Two early-childhood cases of optic neuritis].
AB  - We reported two early-childhood cases suffering from acute optic neuritis (ON).
      Case 1 was a 3-year-old girl, who had a preceding upper respiratory infection,
      headache, nausea and subsequent sudden visual disturbance. Cranial MRI revealed
      multiple T2-elongated lesions in the white matter. She showed two neurological
      relapses including ON, leading to the diagnosis of clinically probable multiple
      sclerosis (MS). Case 2 was a 2-year-old boy, who had an acute onset of visual
      disturbance without any other neurological deficits. MRI with Gd-DTPA enhancement
      revealed not only a disorder of optic nerves but involvement of the white matter
      in the acute phase. It has been suggested that there may be a broad spectrum of
      demyelinating disorders between ON and MS even in early-childhood. Therefore, we
      should bear in mind to the subsequent progression to MS in childhood ON cases
      with silent brain lesions.

PMID- 8753135
TI  - [A case of Smith-Magenis syndrome].
AB  - A boy with an interstitial deletion of the short arm of chromosome 17 was
      reported, with special reference to radiological and electroencephalographic
      findings. Brain MRI showed megacisterna magna caused by cerebellar hypoplasia,
      and suspected cortical dysplasia. Sleep EEG showed humps, spindles, and REM sleep
      patterns. This case performed sleep disturbance. It seems like to tendency of
      awakeness in REM sleep.

PMID- 8753136
TI  - [A case with superficial siderosis of the central nervous system accompanied by
      sensory high tone hearing loss and recurrent headache and vomiting].
AB  - A 13-year-old boy with superficial siderosis of the central nervous system was
      reported. There were many members, including the proband, with sensory high tone
      hearing loss in his maternal family, but they did not have other neurological
      symptoms. Paroxysmal and pulsatile severe headache, and vomiting without aura
      appeared recurrently at the age of 8. His consciousness was alert and no other
      abnormal sign or symptom was seen during the attacks. The electroencephalogram
      and cranial computed tomogram revealed no abnormality. The T2 weighted magnetic
      resonance image of the cranium showed a superficial low intensity zone on the
      cerebellar vermis, frontal and parietal lobes of the cerebrum, and cervical and
      upper portion of the thoracic spinal cord at the age of 12, when he had severe
      headache and vomiting. Cerebrospinal fluid showed xanthochromia with mild
      elevation of the protein level during an attack, and a light bloody appearance
      during the asymptomatic state. The diagnosis of superficial siderosis of the
      central nervous system was made by these findings of magnetic resonance image and
      cerebrospinal fluid. The bleeding sources to the subarachnoid space could not be
      detected by cerebral angiography.

PMID- 8753137
TI  - [The effect of lidocaine tapes on cluster of intractable partial seizures].

PMID- 8753138
TI  - [Effect of high-dose gamma globulin on a case of acute transverse myelitis].

PMID- 8753139
TI  - Bacteriophage T4 expression-packaging-processing vector that encapsidates HIV
      type I GP120-V3 fusion protein inside the head.
AB  - Bacteriophage T4 as an expression-packaging-processing vector has recently been
      developed by using the T4 non-essential capsid scaffold protein IPIII(1-3). The
      IPIII gene was expressed at high level in E. coli from plasmid and was truncated
      at its C-terminus to permit construction of gene fusion in three different
      reading frames of EP-16 vector. Regulated higher-expression PPL reading frame
      vectors were also constructed. Infection of the plasmid-containing bacteria with
      bacteriophage mutants deleted for the IPIII gene showed that viable phage
      encapsidated and proteolytically processed the IPIII fusion proteins. An IPIII
      gene fused to human immunodeficiency virus type I (HIV-1) gp120 loop3 domain (V3)
      IPIII-V3 fusion gene products has been constructed and was packaged and processed
      within viable phage particle. The packaged fusion protein Gp120-V3 may be used
      for production of vaccine in the future.

PMID- 8753140
TI  - Effects of dopamine antagonists and agonist on cultured human Tenon's fibroblast
      cells.
AB  - It was found that long-term therapy with topical antiglaucoma drugs may increase
      the number of fibroblasts and inflammatory cells in the conjunctiva and Tenon's
      capsule then decrease the success of glaucoma filtering surgery. Since some
      dopamine antagonists and agonists are reported to have ocular hypotensive
      effects, they could potentially be used as clinical antiglaucoma agents in
      future. In this study, several dopamine antagonists and agonists were evaluated
      in their effects on the fibroblast proliferation of ocular tissues with cultured
      human ocular Tenon's fibroblast cells. It was found that dopamine antagonists
      inhibited [3H]-thymidine uptake to 10.8%, 14.4%, 42.2% and 72.4% of control in
      domperidone, 28.6%, 67.7%, 96.9% and 99.2% in haloperidol, 9.8%, 18.9%, 103.5%
      and 104.6% in moperone and 9.8%, 24.7%, 70.8% and 96.9% in loxapine respectively,
      while the 0.5% concentration of drugs were dissolved in dimethyl sulfoxide (DMSO)
      followed by dilution in culture medium to final concentrations ranging from
      0.05%, 0.005%, 0.0005% to 0.00005%. In the case of dopamine agonist,
      bromocriptine, the proliferation of cultured human Tenon's fibroblast cells was
      also inhibited for 25.1% of the control at 0.05% concentration and 92.3% of the
      control at 0.00005% concentration. These results indicate that these dopamine
      drugs have a potential long-term application in the treatment of glaucoma without
      having the stimulating effect on the proliferation of human Tenon's fibroblast
      cells.

PMID- 8753141
TI  - Human prolactinomas in cell culture: structure-function correlation and
      indication of early relapse.
AB  - Cell cultures of 7 micro- and 16 macroprolactinomas obtained from twenty-three
      patients (10 males and 13 females) by transsphenoidal adenomectomies were found
      to be capable of secreting hormones in vitro. Prolactin levels in the culture
      media were measured during the culture periods and showed that the high PRL
      levels in culture media may indicate early relapse. Morphological features of
      both micro- and macroprolactinomas in vitro resembled those of the original
      tumors. Most macroprolactinomas harbored densely-granulated cells, while most
      microprolactinomas sparsely-granulated cells. The cell culture techniques
      combined with morphological studies of prolactinomas allow further investigation
      of structure-function correlation in human prolactinomas.

PMID- 8753142
TI  - Study of isometric lifting strength in normal Chinese adults.
AB  - The purposes of this study were to describe norms of isometric lifting strength
      for healthy Chinese adults and to investigate the effects of age, gender, body
      weight, and body height on lifting strength. Three types of lifting (i.e., arm,
      back, and leg lifting) were measured in a sample of 350 Chinese adults (172 men
      and 178 women) aged between 20 and 81 years. A Force Evaluation and Testing
      System (FET 5000) was used for strength measurements with three standard lifting
      positions. The average of two trials for each lifting strength test was used as
      the subjects' test score. The results showed that the greatest strengths for both
      sexes exist aged between late 20's and early 30's, with a general decline
      following thereafter. The magnitude of strength decline with age was most
      prominent in leg lifting strength among all lifting patterns. Males were stronger
      than females in all lifting patterns among the different age groups. All of the
      lifting strengths studied correlated positively with gender, body weight, and
      body height, and negatively with age in the analyses of simple correlation
      coefficients. In addition, stepwise multiple regression analyses showed that sex,
      age and body weight were most predictive of all types of lifting strengths. Body
      height was an effective predictor of back lifting strength. These findings and
      the establishment of data base can provide therapists with an objective
      evaluation regarding lifting strength of individuals for clinical use.

PMID- 8753143
TI  - Maternal and child health services provided by the family physicians in a college
      hospital.
AB  - Traditionally, maternal and child health services in Taiwan have been offered
      mainly by the public community health station in each township. There is a trend
      to integrate these services into the daily practice of physicians in varied
      medical settings. The purpose of this study was to evaluate the work of providing
      the maternal and child health services by family physicians practicing at a
      college hospital. From July 1993 through June 1994, 69 women attending the pre
      marital health examination program and 399 family patients who were in need of
      the maternal and child health services at the Family Medicine Clinic were
      included in this study. Data related to subjects' backgrounds and office visits
      were analyzed retrospectively. About 80% of patients attending pre-marital health
      examinations were satisfied with the scope and process of the services provided.
      Of 399 family patients contacted by letter and telephone, 322 patients (80.7%)
      kept the appointments to visit our clinic. Regarding maternal health services,
      related health education and counselling services were widely provided to female
      family patients. However, the actual implementation rates of breast examination,
      Pap smear test and family planning procedures were only 44.5%, 35.7%, and 23.2%,
      respectively. Factors related to female patients' agreement to do breast
      examination or Pap smear test included their educational level, age, duration of
      being enrolled in family care, and the number of family members under the family
      care. Regarding child health services, vaccinations and periodic health
      examinations were the main services provided by the family physicians. We
      concluded that family physicians in our series are capable of providing maternal
      and child health services to their family patients, and that the actual
      implementation rates of preventive services could be further promoted through
      family physicians' more active attitude and recruiting methods.

PMID- 8753144
TI  - The patterns of dental caries of preschool children in Kaohsiung City Taiwan.
AB  - In order to understand caries patterns, we investigated the severity of caries
      and the distribution of decayed teeth in 1,654 preschool children aged 3-6 years
      old in Kaohsiung, Taiwan. The results of our investigation were as follows: the
      lower second molars had the highest percentage of caries followed by the upper
      central incisors in the deciduous teeth. The distribution of decayed surfaces in
      the upper dentition indicated that the occlusal surface of molars, the labial
      surface of canines, and the mesial and labial surfaces of incisors had relatively
      high percentages of caries in all age groups. In the 3 year-old children, labial
      caries on the four upper anterior teeth and no caries in the lower anterior teeth
      is basically similar to baby bottle tooth decay. Most caries remained in the
      enamel at this stage. Dentin caries and pulp involved caries became more complex
      and multiple surfaces were involved in both 5 and 6 year-old children. We
      therefore suggest that 6, 18, and 30 month-old babies, at the time of
      vaccination, should have an oral examination as well, and the prevention program
      for baby bottle tooth decay plus oral hygiene instructions should also be given
      to the parents. Dentists, pediatricians, gynecologists, and family doctors should
      all participate in the prevention program against baby bottle tooth decay. For 3
      year-old children who already have caries, increasing the filling rate for them
      should be a very important thing to do for pedodontic specialists and general
      dental practitioners alike.

PMID- 8753145
TI  - Medication-taking behavior of the elderly.
AB  - The aim of this study was to examine the medication-taking behavior of older
      adults living in communities. Factors influencing their medication-taking
      behavior were also explored. Data were collected by way of a face-to-face
      interview survey through a random sample of 401 persons over 65 years of age, and
      were analyzed using SPSS computer software. The sample included two groups of
      people, one residing in an urban community and the other in a rural community.
      The results revealed information on the following kinds of medication behavior:
      self-medication, using non-prescription medications, sharing medication,
      forgetting to take medications, misusing medications, being non-compliant, using
      multi-medications, hoarding medications, and combining Western medications with
      traditional therapies. In comparing the differences between the urban and rural
      elderly, the urban elderly had more accurate medication knowledge and displayed
      better medication-taking behavior. An elderly person's age, gender, education
      level, marital status, living status and health belief were found to affect
      his/her medication knowledge and behavior. Education of both health care
      professionals and the general public is urgently needed to ensure the safety of
      taking medication by the elderly.

PMID- 8753146
TI  - Bilateral epidural hematoma in a neonate.
AB  - A skull bone fracture was detected in a neonate immediately after filling down.
      Bilateral epidural hematoma was diagnosed by plain CT scans. Craniotomy and
      evacuation of hematoma was done when the neurological signs were worsening.
      Epidural hematoma was documented communicating, via the fracture site with the
      overlying cephalohematoma. Good recovery was achieved following the operation.
      The longterm follow-up of this patient is mandatory.

PMID- 8753147
TI  - Tourette syndrome and complex partial epilepsy--a case report.
AB  - Controversy exists over the pathophysiology of Tourette syndrome (TS). The case
      reported is a 37-year-old unmarried man suffering from both TS and complex
      partial epilepsy (CPE). He began to have seizures at 2-3 months of age. The CPE
      featured dark vision, dizziness, followed by unresponsiveness, a blank stare,
      occasional loss of posture control, and occasional automatism consisting of going
      to the toilet to urinate. TS gradually began to develop when he was 3-4 years of
      age. The tics were characterized by stereotypic stuttering, vocalization,
      hiccups, grimacing, snorting, and jerky supination of both forearms. EEG sharp
      waves with phase reversal at the left frontotemporal region were present but they
      were not related to the tics. Magnetic resonance imaging revealed atrophy of the
      left temporal and frontal lobes, as well as absence of normal asymmetry of basal
      ganglia. This case supports the theory that TS is related to the left frontal
      lobe, limbic system, and basal ganglia, but contradicts the hypothesis that the
      tics are ictal events.

PMID- 8753148
TI  - Introduction to special section on group therapy and managed care.

PMID- 8753149
TI  - Group psychotherapy and managed behavioral health care: current trends and future
      challenges.
AB  - The rising cost of health care within the private and public sectors has created
      an increased demand for the management of benefit dollars. This trend has
      significant implications for group psychotherapists, as group modalities offer
      cost-effective ways of delivering services to traditional outpatient and
      inpatient populations. Continued cost-containment pressures and increasing
      attention to outcome studies will fuel trends toward briefer, manualized group
      treatments and intensive group outpatient programs as alternatives to
      hospitalization. Quality-based demands will challenge payors to (a) address
      biases against group psychotherapy among providers and patients and (b) integrate
      recent process-and-outcome research in determining the appropriateness of group
      versus individual modalities for particular patients and presenting problems.

PMID- 8753150
TI  - A consideration of factors influencing the utilization of time-limited, short
      term group therapy.
AB  - Previous reviews of the research literature and a new review conducted for this
      article were examined for evidence of the efficacy, applicability, and efficiency
      of time-limited, short-term group therapy (TSGT). Strong evidence for all three
      factors was found. Additional patient and therapist factors influence the
      effectiveness and utilization of TSGT in clinical settings, however. Some are
      analogous to criteria routinely considered in the use of medication such as "ease
      of administration" and "side effects." Others are particularly relevant to
      therapists, such as lack of training and experience, organizational difficulties,
      and negative reactions to managed-care initiatives. Optimal matching of patient
      and treatment also affects treatment decisions. Implications for clinicians and
      administration are considered.

PMID- 8753151
TI  - A model of time-effective group psychotherapy for patients with personality
      disorders: the clinical model.
AB  - This article describes a model of time-limited psychotherapy for patients with
      personality disorders that emphasizes the group as a social microcosm. The
      patient population described is relatively high functioning, although the
      majority of the group members meet DSM-III-R (American Psychiatric Association,
      1987) criteria for an Axis II diagnosis. The clinical model's key theoretical
      concepts, for example, interpersonal focus; active therapist stance; emphasis on
      group interaction and processes; use of time limits; primary care/intermittent
      treatment philosophy; and emphasis on patients' strengths, goals, and resources
      are described. The relationships between the phases of group therapy and the key
      theoretical concepts are delineated.

PMID- 8753153
TI  - Large group treatment of severely disturbed/conduct-disordered adolescents.
AB  - Group psychotherapy is an effective treatment modality for many teenagers.
      Although group treatment usually refer to a group of 10 or fewer members, this
      article argues that larger groups are an even better choice when the members are
      severely disturbed/conduct-disordered adolescents. Although challenging and
      exciting, group psychotherapy with these youngsters can be a difficult task.
      Their narcissistic vulnerability, impaired ability to mediate between internal
      and external events, and their propensity for violently expressing their
      frustration, rage, and despair demand a structure that is both firm and flexible,
      and carefully planned strategies. A structure and technique that maximizes safety
      during and following group meetings, that positively influences behavior, and
      that may facilitate an altered perception of self and others are discussed.

PMID- 8753152
TI  - Time-limited group psychotherapy for patients with personality disorders:
      outcomes and dropouts.
AB  - This study reports on the time-limited (18-month long) group therapy of 49
      outpatients, most of whom were diagnosed with DSM-III-R, Axis II personality
      disorders (American Psychiatric Association, 1987). Although many patients did
      not complete the full course of treatment, those who did experienced many areas
      of change. Completers reported substantial changes in self-esteem,
      symptomatology, and diagnosability on Axis II. This type of group treatment
      appears to be a promising mode of intervention for those with personality
      disorders.

PMID- 8753155
TI  - Combined behavioral and psychodynamic supervision of social skills training
      groups.

PMID- 8753154
TI  - Group therapy as an effective treatment modality for people of color.
AB  - The unique benefits for group therapy are examined with special emphasis on the
      treatment of blacks and Latinos. Because of racial prejudice, economic
      exploitation, and negative stereotypes, group forces have been especially
      detrimental to the personality development of people of color. The group
      therapist attempts to harness these powerful group forces and use them
      therapeutically, thus enabling people of color to relate better to others while
      retaining their own autonomy. Racial differences can intensely affect diagnosis,
      transference, countertransference, and the "real relationship." Distinctions
      between cultural and functional paranoia are particularly relevant in interracial
      groups. Implications for training group therapists are also explored.

PMID- 8753156
TI  - The group as an idealized internal object.

PMID- 8753157
TI  - Foxy in the henhouse.

PMID- 8753158
TI  - It's time to take off the gag. TMA takes progressive action to head off managed
      care gag rules.

PMID- 8753159
TI  - Building for the future. Memphis integrated delivery systems provide a glimpse of
      the future for Tennessee doctors.

PMID- 8753160
TI  - Grading TennCare.

PMID- 8753161
TI  - Complication during arthroscopy.

PMID- 8753162
TI  - Diagnosis of Meckel's diverticulum by computerized tomography.

PMID- 8753163
TI  - Antiphospholipid and anticentromere antibodies occurring together in a patient
      with pulmonary hypertension.

PMID- 8753165
TI  - Project TEACH in the school system. Together Educating and Coordinating Health.

PMID- 8753164
TI  - An abdominal hernia secondary to blunt trauma.

PMID- 8753166
TI  - [Bleeding time].

PMID- 8753167
TI  - [Activated partial thromboplastin time (APTT), partial thromboplastin time
      (PTT)].

PMID- 8753168
TI  - [Prothrombin time (PT)].

PMID- 8753169
TI  - [Thrombotest (TBT), hepaplastin test (HPT)].

PMID- 8753170
TI  - [Fibrinogen (factor I)].

PMID- 8753171
TI  - [Soluble fibrin monomer complex (SFMC)].

PMID- 8753172
TI  - [Fibrin/fibrinogen degradation products (FDP)].

PMID- 8753173
TI  - [FDP-E fraction].

PMID- 8753174
TI  - [D dimer].

PMID- 8753175
TI  - [Fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 (FPB beta 15-42)].

PMID- 8753176
TI  - [Antithrombin III (AT III)].

PMID- 8753177
TI  - [Thrombin antithrombin III complex (TAT)].

PMID- 8753178
TI  - [Plasminogen (PG), plasmin (PM)].

PMID- 8753179
TI  - [alpha 2-Plasmin inhibitor-plasmin complex (PIC)].

PMID- 8753180
TI  - [Tissue-plasminogen activator (t-PA)].

PMID- 8753181
TI  - [Plasminogen activator inhibitor-1 (PAI-1)].

PMID- 8753182
TI  - [Factor V].

PMID- 8753183
TI  - [Factor VII].

PMID- 8753184
TI  - [Factor VIII].

PMID- 8753186
TI  - [Factor X].

PMID- 8753185
TI  - [Factor IX].

PMID- 8753187
TI  - [Factor XI].

PMID- 8753188
TI  - [Factor XII (Hageman factor)].

PMID- 8753189
TI  - [Factor XIII].

PMID- 8753191
TI  - [Factor IX inhibitor].

PMID- 8753190
TI  - [Factor VIII inhibitors].

PMID- 8753192
TI  - [von Willebrand factor (vWF)].

PMID- 8753193
TI  - [beta-Thromboglobulin (beta-TG)].

PMID- 8753194
TI  - [Platelet factor 4 (PF 4)].

PMID- 8753195
TI  - [Protein C].

PMID- 8753196
TI  - [Protein S].

PMID- 8753197
TI  - [Heparin cofactor II (HC II)].

PMID- 8753199
TI  - [Protein Z].

PMID- 8753198
TI  - [Activated protein C-protein C inhibitor complex (APC-PCI complex)].

PMID- 8753200
TI  - [Thrombomodulin (TM)].

PMID- 8753201
TI  - [Thrombelastography].

PMID- 8753203
TI  - [Circulating anticoagulant].

PMID- 8753202
TI  - [Platelet aggregation].

PMID- 8753204
TI  - [Abnormal fibrinogen].

PMID- 8753205
TI  - [Tissue factor (TF)].

PMID- 8753206
TI  - [Tissue factor pathway inhibitor (TFPI)].

PMID- 8753207
TI  - [Fibronectin].

PMID- 8753208
TI  - [Fletcher factor, Fitzgerald factor].

PMID- 8753209
TI  - [Hemoglobin (Hb) and its components].

PMID- 8753211
TI  - [Carboxyhemoglobin].

PMID- 8753210
TI  - [Hemoglobinopathy].

PMID- 8753212
TI  - [Sulfhemoglobin].

PMID- 8753213
TI  - [Terminal deoxynucleotidyl transferase (TdT)].

PMID- 8753214
TI  - [Hexosaminidase isoenzyme pattern in leukemia].

PMID- 8753215
TI  - [Asialo GM1].

PMID- 8753216
TI  - [Arginase].

PMID- 8753217
TI  - [2-5 Oligoadenylate synthetase].

PMID- 8753218
TI  - [Glucose-6-phosphate dehydrogenase (G6PD)].

PMID- 8753219
TI  - [Phosphoglucomutase (PGM)].

PMID- 8753220
TI  - [Measurement of glutathione].

PMID- 8753221
TI  - [Erythrocyte glutathione reductase (EGR)].

PMID- 8753222
TI  - [Neutrophil alkaline phosphatase (NAP) score].

PMID- 8753223
TI  - [Cytochrome b5 reductase].

PMID- 8753224
TI  - [2,3-Diphosphoglycerate (2,3-DPG)].

PMID- 8753226
TI  - [Isoenzyme of nonspecific esterase in hemopoietic cells].

PMID- 8753225
TI  - [Red cell glycolytic intermediates].

PMID- 8753228
TI  - [Acid phosphatase].

PMID- 8753227
TI  - [Nucleotides].

PMID- 8753230
TI  - [Red cell enzyme activities].

PMID- 8753229
TI  - [Myeloperoxidase].

PMID- 8753231
TI  - [Erythrocyte transketolase].

PMID- 8753232
TI  - [Human neutrophil elastase].

PMID- 8753233
TI  - [Growth hormone (GH, hGH)].

PMID- 8753234
TI  - [IGF I, IGF II].

PMID- 8753235
TI  - [Prolactin (PRL)].

PMID- 8753236
TI  - [Adrenocorticotropic hormone (ACTH)].

PMID- 8753237
TI  - [Luteinizing hormone (LH)].

PMID- 8753238
TI  - [Follicle stimulating hormone (FSH)].

PMID- 8753239
TI  - [Somatostatin].

PMID- 8753240
TI  - [Thyroid stimulating hormone (TSH)].

PMID- 8753241
TI  - [Thyrotropin releasing hormone (TRH)].

PMID- 8753242
TI  - [Vasopressin (anti-diuretic hormone: ADH)].

PMID- 8753243
TI  - [Oxytocin (OT)--measurement and its clinical implication].

PMID- 8753244
TI  - [Lipotropin (LPH) and melanocyte-stimulating hormone (MSH)].

PMID- 8753245
TI  - [Neurotensin].

PMID- 8753246
TI  - [beta-Endorphin].

PMID- 8753247
TI  - [Enkephalin].

PMID- 8753248
TI  - [Corticotropin-releasing hormone (CRH)].

PMID- 8753249
TI  - [Gonadotropin releasing hormone (GnRH)].

PMID- 8753250
TI  - [Growth hormone-releasing hormone (GHRH)].

PMID- 8753251
TI  - [Growth hormone-binding protein].

PMID- 8753252
TI  - [Neurophysin].

PMID- 8753253
TI  - [Total triiodothyronine (total T3)].

PMID- 8753254
TI  - [Free T3 (FT3)].

PMID- 8753255
TI  - [Reverse T3 (rT3)].

PMID- 8753256
TI  - [T3 uptake (T3U)].

PMID- 8753257
TI  - [Total thyroxine (T4)].

PMID- 8753258
TI  - [Free thyroxin (FT4)].

PMID- 8753259
TI  - [Thyroglobulin (Tg)].

PMID- 8753260
TI  - [Thyroxine binding globulin (TBG)].

PMID- 8753261
TI  - [Monoiodothyronine (T1)].

PMID- 8753262
TI  - [Di-iodothyronine (T2)].

PMID- 8753263
TI  - [Parathyroid hormone (PTH)].

PMID- 8753264
TI  - [Parathyroid hormone-related protein (PTHrP)].

PMID- 8753265
TI  - [Calcitonin (CT)].

PMID- 8753266
TI  - [Calcitonin gene-related peptide (CGRP)].

PMID- 8753267
TI  - [TSH receptor antibody].

PMID- 8753268
TI  - [Thyroglobulin antibodies].

PMID- 8753269
TI  - [Microsomal antibodies].

PMID- 8753270
TI  - [Thyroxine binding capacity (TBC)].

PMID- 8753272
TI  - [Urinary 17-ketogenic steroids (17-KGS) and 17-KGS fractions].

PMID- 8753271
TI  - [Urinary 17-ketosteroids (17-KS) and 17-KS fractions].

PMID- 8753273
TI  - [17-Hydroxycorticoids (17-OHCS) and its fractions].

PMID- 8753274
TI  - [11-Hydroxycorticosteroid (11-OHCS)].

PMID- 8753275
TI  - [Cortisol].

PMID- 8753276
TI  - [11-Deoxycortisol].

PMID- 8753277
TI  - [21-Deoxycortisol].

PMID- 8753278
TI  - [Corticosterone].

PMID- 8753279
TI  - [11-Deoxycorticosterone (DOC), 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) and
      19-nor-deoxycorticosterone (19-nor-DOC)].

PMID- 8753280
TI  - [Dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S)].

PMID- 8753281
TI  - [Pregnenolone].

PMID- 8753282
TI  - [18-Hydroxycortisol (18-OH-F) and 18-oxocortisol (18-oxoF)].

PMID- 8753283
TI  - [17-Hydroxyprogesterone].

PMID- 8753284
TI  - [17 alpha-hydroxypregnenolone].

PMID- 8753285
TI  - [6 beta-Hydroxycortisol].

PMID- 8753286
TI  - [Aldosterone].

PMID- 8753287
TI  - [Androsterone].

PMID- 8753288
TI  - [Androstenedione].

PMID- 8753289
TI  - [Corticosteroid-binding globulin (CBG): measurement and its clinical
      implication].

PMID- 8753290
TI  - [Urinary tetrahydro-11-deoxycortisol (THS)].

PMID- 8753291
TI  - [18-Hydroxycorticosterone (18-OH-B)].

PMID- 8753292
TI  - [Catecholamine (CA)].

PMID- 8753293
TI  - [Metanephrine (M) and normetanephrine (NM)].

PMID- 8753294
TI  - [3,4-Dihydroxyphenylalanine (DOPA)].

PMID- 8753295
TI  - [Homovanillic acid (HVA)].

PMID- 8753296
TI  - [Vanillylmandelic acid (VMA)].

PMID- 8753297
TI  - [Serotonin].

PMID- 8753298
TI  - [5-Hydroxyindole acetic acid (5HIAA)].

PMID- 8753299
TI  - [3-Methoxy-4-hydroxyphenylglycol (MHPG)].

PMID- 8753300
TI  - [3,4-Dihydroxyphenylacetic acid (DOPAC)].

PMID- 8753301
TI  - [Adrenergic receptors].

PMID- 8753302
TI  - [Chromogranin A].

PMID- 8753303
TI  - [Dopamine-beta-hydroxylase (DBH)].

PMID- 8753304
TI  - [Estrogen: estrone (E1), estradiol (E2) and estriol (E3)].

PMID- 8753305
TI  - [Estetrol (E4)].

PMID- 8753306
TI  - [Sex hormone-binding globulin (SHBG)].

PMID- 8753307
TI  - [Progesterone].

PMID- 8753308
TI  - [Pregnanediol (P2)].

PMID- 8753309
TI  - [Pregnanetriol (P3)].

PMID- 8753310
TI  - [Testosterone, free testosterone].

PMID- 8753311
TI  - [Clinical application of dihydrotestosterone (DHT) determination].

PMID- 8753312
TI  - [Human chorionic gonadotropin (hCG) and subunits].

PMID- 8753313
TI  - [Human placental lactogen (hPL)].

PMID- 8753314
TI  - [Androstanediol].

PMID- 8753315
TI  - [Catechol estrogen].

PMID- 8753316
TI  - [Proinsulin].

PMID- 8753317
TI  - [C-peptide (CPR)].

PMID- 8753318
TI  - [Gastrin].

PMID- 8753319
TI  - [Vasoactive intestinal polypeptide (VIP)].

PMID- 8753320
TI  - [Substance P].

PMID- 8753321
TI  - [Secretin].

PMID- 8753322
TI  - [Motilin].

PMID- 8753324
TI  - [Pancreatic polypeptide (PP)].

PMID- 8753323
TI  - [Cholecystokinin-pancreozymin (CCK-PZ)].

PMID- 8753325
TI  - [Gastric inhibitory polypeptide (GIP)].

PMID- 8753326
TI  - [Enteroglucagon].

PMID- 8753327
TI  - [Plasma IRI--assay method and its significance in clinical medicine].

PMID- 8753328
TI  - [Pancreatic glucagon (IRG)].

PMID- 8753329
TI  - [Human pancreatic polypeptide (hPP)].

PMID- 8753330
TI  - [Functional tests on insulin receptors].

PMID- 8753331
TI  - [Examination of glucocorticoid receptor].

PMID- 8753332
TI  - [Plasma renin activity (PRA)].

PMID- 8753333
TI  - [Plasma renin concentration (PRC)].

PMID- 8753334
TI  - [Active renin concentration (ARC)].

PMID- 8753335
TI  - [Angiotensinogen (renin substrate)].

PMID- 8753336
TI  - [Angiotensin I].

PMID- 8753337
TI  - [Angiotensin II].

PMID- 8753338
TI  - [Prostaglandin E1 and its metabolites].

PMID- 8753339
TI  - [Prostaglandin E2 and its metabolites].

PMID- 8753340
TI  - [Prostacyclin and metabolites].

PMID- 8753341
TI  - [Prostaglandin F2 alpha and its metabolites].

PMID- 8753342
TI  - [Thromboxane B2 (TXB2)].

PMID- 8753343
TI  - [Kallikrein, kininogen and kinin in health and disease].

PMID- 8753344
TI  - [Cyclic AMP (cAMP)].

PMID- 8753345
TI  - [Cyclic GMP (cGMP)].

PMID- 8753346
TI  - [Histamine].

PMID- 8753347
TI  - [Human atrial natriuretic peptide (hANP), human brain natriuretic peptide
      (hBNP)].

PMID- 8753348
TI  - [Erythropoietin].

PMID- 8753349
TI  - [Osteocalcin].

PMID- 8753350
TI  - [Endothelin].

PMID- 8753351
TI  - [Leukotriene].

PMID- 8753352
TI  - [Osteoclast activating factor (OAF)].

PMID- 8753353
TI  - [Melatonin].

PMID- 8753354
TI  - [Tumor necrosis factor (TNF)].

PMID- 8753355
TI  - [Interleukin 1 (IL-1)].

PMID- 8753356
TI  - [Interleukin-2 (IL-2)].

PMID- 8753357
TI  - [Interleukin-3 (IL-3)].

PMID- 8753358
TI  - [Interleukin-4 (IL-4)].

PMID- 8753359
TI  - [Interleukin-5 (IL-5)].

PMID- 8753360
TI  - [Interleukin-6 (IL-6)].

PMID- 8753361
TI  - [Interleukin-8, 9 (IL-8, IL-9)].

PMID- 8753362
TI  - [Interferon].

PMID- 8753363
TI  - [Granulocyte colony-stimulating factor (G-CSF)].

PMID- 8753365
TI  - [Granulocyte-macrophage colony stimulating factor (GM-CSF)].

PMID- 8753364
TI  - [Macrophage colony-stimulating factor (M-CSF)].

PMID- 8753366
TI  - [Epidermal growth factor (EGF)].

PMID- 8753367
TI  - [Fibroblast growth factor (FGF)].

PMID- 8753368
TI  - [Macrophage chemotactic factor (MCF)].

PMID- 8753369
TI  - [Transforming growth factor (TGF)].

PMID- 8753370
TI  - [Hepatocyte growth factor (HGF)].

PMID- 8753371
TI  - [Platelet-derived growth factor (PDGF)].

PMID- 8753372
TI  - [Lymphotoxin (LT)].

PMID- 8753373
TI  - [Present and future of clinical laboratory].

PMID- 8753374
TI  - [The concept of normal values (reference values) and interpretation of laboratory
      results].

PMID- 8753375
TI  - [Determination of normal values (reference values, reference intervals) on age,
      sex and races].

PMID- 8753376
TI  - [Significance of assigning the reference ranges of laboratory tests in children
      at different age].

PMID- 8753377
TI  - [Introduction of rapid testing including pre-examination testing system and its
      problems].

PMID- 8753378
TI  - [General concept of quality control and its view on future].

PMID- 8753379
TI  - [Standardization in clinical laboratory].

PMID- 8753381
TI  - [Sampling and preservation of test materials].

PMID- 8753380
TI  - [Clinical laboratory system as a part of hospital information system].

PMID- 8753382
TI  - [Chemi- and bio-luminescent immunoassay].

PMID- 8753383
TI  - [Urinalysis with reagent strips--analytes, methodology and clinical
      significance].

PMID- 8753384
TI  - [Urine protein and its fractionation].

PMID- 8753386
TI  - [Urine sugar].

PMID- 8753385
TI  - [Microalbuminuria--laboratory methods and implications].

PMID- 8753387
TI  - [Ketone bodies in urine].

PMID- 8753388
TI  - [Urinary urobilinogen].

PMID- 8753389
TI  - [Urinary bilirubin].

PMID- 8753390
TI  - [Bence Jones protein--detection and clinical aspects].

PMID- 8753391
TI  - [Protein 1 (Clara cell 10 kDa protein)].

PMID- 8753392
TI  - [Urinary Tamm-Horsfall protein (THP)].

PMID- 8753393
TI  - [Plasma proteins].

PMID- 8753394
TI  - [Thymol turbidity test (TTT)].

PMID- 8753395
TI  - [Zinc sulfate turbidity test (ZTT)].

PMID- 8753397
TI  - [kappa Light chain].

PMID- 8753398
TI  - [Calcium-binding proteins].

PMID- 8753396
TI  - [Alpha 1-T glycoprotein].

PMID- 8753399
TI  - [Collagen, procollagen peptide].

PMID- 8753400
TI  - [Prealbumin].

PMID- 8753401
TI  - [alpha 1-Microglobulin (protein HC)].

PMID- 8753402
TI  - [alpha 1-Antitrypsin (alpha 1-AT)].

PMID- 8753403
TI  - [Alpha 1-antichymotrypsin (ACT)].

PMID- 8753404
TI  - [alpha 1-Acid glycoprotein].

PMID- 8753405
TI  - [Retinol-binding protein (RBP)].

PMID- 8753406
TI  - [alpha 2-Macroglobulin].

PMID- 8753407
TI  - [Haptoglobin].

PMID- 8753408
TI  - [Ceruloplasmin].

PMID- 8753409
TI  - [Hemopexin].

PMID- 8753410
TI  - [Transferrin].

PMID- 8753411
TI  - [beta 2-Microglobulin].

PMID- 8753412
TI  - [C-reactive protein (CRP)].

PMID- 8753413
TI  - [Serum amyloid A (SAA)].

PMID- 8753414
TI  - [Myoglobin].

PMID- 8753415
TI  - [Myosin light chain].

PMID- 8753416
TI  - [Troponin T].

PMID- 8753417
TI  - [Ferritin].

PMID- 8753418
TI  - [Vitronectin].

PMID- 8753419
TI  - [Measurement of serum laminin--in reference to diseases].

PMID- 8753420
TI  - [Type IV collagen].

PMID- 8753421
TI  - [Creatine kinase (CK)].

PMID- 8753422
TI  - [Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)].

PMID- 8753423
TI  - [Lactate dehydrogenase].

PMID- 8753424
TI  - [Alkaline phosphatase and its isozyme].

PMID- 8753425
TI  - [gamma-Glutamyl transpeptidase (gamma GTP)].

PMID- 8753426
TI  - [Aldolase].

PMID- 8753427
TI  - [Monoamine oxidase].

PMID- 8753428
TI  - [Cholinesterase].

PMID- 8753429
TI  - [Guanase].

PMID- 8753430
TI  - [Adenosine deaminase].

PMID- 8753431
TI  - [Leucine aminopeptidase (LAP)].

PMID- 8753432
TI  - [Cystine aminopeptidase].

PMID- 8753433
TI  - [Serum amylase].

PMID- 8753434
TI  - [Serum trypsin].

PMID- 8753435
TI  - [Pancreatic secretory trypsin inhibitor (PSTI)].

PMID- 8753436
TI  - [Chymotrypsin].

PMID- 8753437
TI  - [Elastase].

PMID- 8753438
TI  - [5'-Nucleotidase].

PMID- 8753439
TI  - [Pancreatic phospholipase A2].

PMID- 8753440
TI  - [Acid phosphatase].

PMID- 8753441
TI  - [Glutamate dehydrogenase].

PMID- 8753442
TI  - [Isocitrate dehydrogenase (ICD)].

PMID- 8753443
TI  - [Ornithine carbamoyl transferase (OCT)].

PMID- 8753444
TI  - [beta-Glucuronidase].

PMID- 8753445
TI  - [Catalase].

PMID- 8753446
TI  - [Lysozyme (muramidase)].

PMID- 8753447
TI  - [Glycylproline dipeptidyl aminopeptidase (GPDAP)].

PMID- 8753448
TI  - [Pyruvate kinase].

PMID- 8753449
TI  - [Sorbitol dehydrogenase (SDH)].

PMID- 8753450
TI  - [Malate dehydrogenase (MDH)].

PMID- 8753451
TI  - [Collagenase].

PMID- 8753452
TI  - [Prolyl hydroxylase].

PMID- 8753453
TI  - [Mn-superoxide dismutase].

PMID- 8753454
TI  - [Angiotensin I converting enzyme].

PMID- 8753455
TI  - [Arylsulfatase].

PMID- 8753456
TI  - [Glyceraldehyde reductase].

PMID- 8753457
TI  - [beta-Hexosaminidase].

PMID- 8753458
TI  - [C1-inhibitor (C1-INH)].

PMID- 8753459
TI  - [beta 1,4-Galactosyltransferase].

PMID- 8753460
TI  - [Arylamidase].

PMID- 8753461
TI  - [Arylesterase (ArE)].

PMID- 8753462
TI  - [Argininosuccinate synthetase (ASS)].

PMID- 8753463
TI  - [Alcohol dehydrogenase (ADH)].

PMID- 8753464
TI  - [Galactosyltransferase].

PMID- 8753465
TI  - [Glutathione peroxidase].

PMID- 8753466
TI  - [Enzyme-linked immunoglobulin].

PMID- 8753467
TI  - [Pancreatic lipase].

PMID- 8753468
TI  - [Phosphofructokinase (PFK)].

PMID- 8753469
TI  - [Macroamylase].

PMID- 8753470
TI  - [Alanine aminopeptidase in urine].

PMID- 8753471
TI  - [Urinary N-acetyl-beta-D-glucosaminidase].

PMID- 8753472
TI  - [Isozymes of DNase I].

PMID- 8753473
TI  - [Urinary alkaline phosphatases].

PMID- 8753474
TI  - [Creatine].

PMID- 8753476
TI  - [Uric acid].

PMID- 8753475
TI  - [Creatinine and its clinical significance].

PMID- 8753477
TI  - [Blood urea nitrogen, non-protein nitrogen].

PMID- 8753478
TI  - [Ammonia nitrogen].

PMID- 8753479
TI  - [Free amino acids].

PMID- 8753480
TI  - [Aminobutyric acid].

PMID- 8753481
TI  - [Hydroxyproline].

PMID- 8753482
TI  - [Methylhistidine].

PMID- 8753483
TI  - [Guanidino compound derivation].

PMID- 8753484
TI  - [Polyamine and ornithine decarboxylase].

PMID- 8753485
TI  - [Oxypurine].

PMID- 8753486
TI  - [Carnitine].

PMID- 8753488
TI  - [Formiminoglutamic acid (FIGLU)].

PMID- 8753487
TI  - [Purine derivatives].

PMID- 8753489
TI  - [Biochemical markers of bone turnover in urine--pyridinoline, deoxypyridinoline
      and aminoterminal cross-links of type I collagen].

PMID- 8753490
TI  - [Glucose].

PMID- 8753491
TI  - [Galactose].

PMID- 8753492
TI  - [Fructose].

PMID- 8753493
TI  - [Sorbitol].

PMID- 8753494
TI  - [Glycated Hb (glycated hemoglobin)].

PMID- 8753495
TI  - [Fructosamine].

PMID- 8753496
TI  - [Glycated albumin].

PMID- 8753498
TI  - [Xylitol].

PMID- 8753497
TI  - [1,5-Anhydroglucitol (1,5 AG)].

PMID- 8753499
TI  - [Glycosaminoglycans].

PMID- 8753501
TI  - [Neuraminic acid].

PMID- 8753500
TI  - [Glycated lipoproteins].

PMID- 8753502
TI  - [Proteoglycans].

PMID- 8753503
TI  - [Mannose].

PMID- 8753504
TI  - [Lactic acid].

PMID- 8753505
TI  - [Pyruvate].

PMID- 8753506
TI  - [Acetate].

PMID- 8753507
TI  - [Oxalic acid].

PMID- 8753508
TI  - [Citric acid].

PMID- 8753509
TI  - [Methylmalonic acid].

PMID- 8753510
TI  - [Ketone bodies: measurement and its clinical significance].

PMID- 8753511
TI  - [Triglyceride].

PMID- 8753512
TI  - [Free fatty acids and its species].

PMID- 8753513
TI  - [Cholesterol].

PMID- 8753514
TI  - [HDL-cholesterol].

PMID- 8753515
TI  - [Phospholipids and its fractions].

PMID- 8753516
TI  - [Lipid peroxides].

PMID- 8753517
TI  - [Lipoprotein and lipoprotein fractions].

PMID- 8753518
TI  - [Lipoprotein-X (LP-X)].

PMID- 8753519
TI  - [The measurements of lipoprotein lipase activity].

PMID- 8753520
TI  - [Hepatic triglyceride lipase].

PMID- 8753521
TI  - [Lecithin-cholesterol acyltransferase (LCAT)].

PMID- 8753523
TI  - [Apolipoproteins and their fractions].

PMID- 8753522
TI  - [Lipoprotein (a) and mid-band lipoprotein].

PMID- 8753524
TI  - [Chylomicron].

PMID- 8753525
TI  - [Serum bile acids and their profile].

PMID- 8753526
TI  - [Lipid transfer protein].

PMID- 8753527
TI  - [Glycolipids].

PMID- 8753528
TI  - [Phospholipase A].

PMID- 8753529
TI  - [Retinyl palmitate].

PMID- 8753530
TI  - [Carotenoids].

PMID- 8753531
TI  - [Vitamin A (retinoids)].

PMID- 8753532
TI  - [Vitamin B1 (thiamin)].

PMID- 8753533
TI  - [Vitamin B2 (riboflavin)].

PMID- 8753534
TI  - [Pantothenic acid].

PMID- 8753535
TI  - [Vitamin B6 (pyridoxine)].

PMID- 8753536
TI  - [Vitamin B12].

PMID- 8753537
TI  - [Vitamin C (ascorbic acid)].

PMID- 8753538
TI  - [Vitamin D and its metabolites].

PMID- 8753539
TI  - [Vitamin E (tocopherol)].

PMID- 8753540
TI  - [Vitamin K].

PMID- 8753541
TI  - [Folic acid].

PMID- 8753542
TI  - [Nicotinic acid].

PMID- 8753543
TI  - [Biotin (vitamin H)].

PMID- 8753544
TI  - [Inositol].

PMID- 8753545
TI  - [Vitamin D-binding protein (Gc-globulin)].

PMID- 8753546
TI  - [Ubiquinone (CoQ)].

PMID- 8753547
TI  - [Sodium].

PMID- 8753548
TI  - [Potassium].

PMID- 8753549
TI  - [Chloride].

PMID- 8753550
TI  - [Magnesium].

PMID- 8753551
TI  - [Calcium].

PMID- 8753552
TI  - [Inorganic phosphate in serum and urine].

PMID- 8753553
TI  - [Osmolality].

PMID- 8753554
TI  - [Base excess and buffer base].

PMID- 8753555
TI  - [Plasma bicarbonate].

PMID- 8753556
TI  - [Arterial carbon dioxide tension].

PMID- 8753557
TI  - [Arterial oxygen tension and oxygen saturation].

PMID- 8753558
TI  - [Arterial pH].

PMID- 8753559
TI  - [Iron].

PMID- 8753560
TI  - [Total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC)].

PMID- 8753561
TI  - [Copper].

PMID- 8753562
TI  - [Zinc].

PMID- 8753563
TI  - [Aluminium].

PMID- 8753564
TI  - [Lead].

PMID- 8753565
TI  - [Chromium].

PMID- 8753566
TI  - [Cadmium].

PMID- 8753567
TI  - [Manganese].

PMID- 8753568
TI  - [Nickel (Ni)].

PMID- 8753569
TI  - [Arsenic (As)].

PMID- 8753570
TI  - [Mercury].

PMID- 8753571
TI  - [Cobalt].

PMID- 8753572
TI  - [Selenium].

PMID- 8753573
TI  - [Bismuth].

PMID- 8753574
TI  - [Bilirubin].

PMID- 8753575
TI  - [Biliverdin].

PMID- 8753576
TI  - [Porphyrin].

PMID- 8753578
TI  - [delta-Aminolevulinic acid synthase(ALAS)].

PMID- 8753577
TI  - [delta-Aminolevulinic acid (ALA)].

PMID- 8753579
TI  - [delta-Aminolevulinic acid dehydratase].

PMID- 8753580
TI  - [Porphobilinogen deaminase (PBGD)].

PMID- 8753581
TI  - [Dipyrrole bile pigments].

PMID- 8753582
TI  - [Clinical evaluation of therapeutic drug monitoring].

PMID- 8753583
TI  - [Drug screening in clinical toxicology and analytical doping control in sports].

PMID- 8753584
TI  - [Carbamazepine].

PMID- 8753585
TI  - [Clonazepam, nitrazepam, diazepam].

PMID- 8753586
TI  - [Ethosuximide].

PMID- 8753587
TI  - [Valproic acid].

PMID- 8753588
TI  - [Phenobarbital].

PMID- 8753589
TI  - [Phenytoin].

PMID- 8753590
TI  - [Primidone].

PMID- 8753591
TI  - [Zonisamide].

PMID- 8753592
TI  - [Tricyclic antidepressants (imipramine, desipramine, amitriptyline,
      nortriptyline)].

PMID- 8753593
TI  - [Haloperidol].

PMID- 8753594
TI  - [Lithium carbonate].

PMID- 8753595
TI  - [Digitoxin].

PMID- 8753596
TI  - [Digoxin].

PMID- 8753597
TI  - [Procainamide].

PMID- 8753598
TI  - [Quinidine].

PMID- 8753599
TI  - [Diuretics].

PMID- 8753600
TI  - [Theophylline].

PMID- 8753601
TI  - [Calcium antagonist].

PMID- 8753602
TI  - [Alpha-blocker].

PMID- 8753603
TI  - [Beta-blocking agents].

PMID- 8753604
TI  - [Lidocaine hydrochloride].

PMID- 8753605
TI  - [Drug of nitrate and nitrite].

PMID- 8753606
TI  - [Disopyramide, mexiletine, aprindine].

PMID- 8753607
TI  - [Inhibitors of renin-angiotensin system].

PMID- 8753608
TI  - [Aminoglycosides].

PMID- 8753609
TI  - [Antituberculosis drug].

PMID- 8753610
TI  - [Antifungal drugs].

PMID- 8753611
TI  - [Fluoroquinolone].

PMID- 8753612
TI  - [Sulfa drugs].

PMID- 8753613
TI  - [Concentration of cephems in sputum from patients with pulmonary infection:
      relationship between MICs of pathogenic bacteria, levels of antibiotic and
      efficacy].

PMID- 8753614
TI  - [Macrolide].

PMID- 8753615
TI  - [Vancomycin].

PMID- 8753616
TI  - [Non-steroidal anti-inflammatory drugs (NSAIDs)].

PMID- 8753617
TI  - [Synthetic steroids].

PMID- 8753618
TI  - [Salicylic acid].

PMID- 8753619
TI  - [Anticancer drugs].

PMID- 8753620
TI  - [Methotrexate (MTX)].

PMID- 8753621
TI  - [Cyclosporine].

PMID- 8753622
TI  - [Heparin].

PMID- 8753623
TI  - [Paraquat and diquat poisoning].

PMID- 8753624
TI  - [Inulin].

PMID- 8753625
TI  - [Indocyanine green (ICG)].

PMID- 8753626
TI  - [Sodium thiosulfate clearance].

PMID- 8753627
TI  - [Paraaminohippuric acid clearance].

PMID- 8753628
TI  - [Phenolsulfonphthalein (PSP)].

PMID- 8753629
TI  - [BT-PABA test].

PMID- 8753630
TI  - A public health bicentennary.

PMID- 8753631
TI  - Adolescent health: moving from prevention to promotion through a quality of life
      approach.

PMID- 8753632
TI  - [Ten anti-commandments in epidemiology or how to fail in epidemiology].

PMID- 8753633
TI  - Funding system incentives and the restructuring of health care.
AB  - The 1970s and 1980s were decades of rapid growth in health care services and
      expenditures in Canada. Numerous government sponsored reports laid our principles
      for restructured health services delivery. These principles included directions
      such as community orientation, continuity of care and health promotion. The
      principles were similar, and so were the results: throughout Canada there has
      been limited action on these principles.

PMID- 8753634
TI  - Postpartum safety and satisfaction following early discharge.
AB  - Two Ontario sites were involved in the evaluation of an obstetrical discharge
      program. Before program implementation a group of eligible women were enrolled as
      the preprogram control group (n = 542). During the program, eligible women who
      agreed to early discharge (ED) became the ED group (n = 319), and those opting
      not to go home early but consenting to participate in the evaluation became the
      concurrent group (n = 456). All groups were mailed a self-administered postpartum
      questionnaire. On demographic characteristics, safety and satisfaction, the ED
      group was comparable to the concurrent group. Hospital readmission rates did not
      differ across groups after stratification by site or hospital. Multiple
      classification analyses revealed a similar pattern for overall satisfaction
      levels. This unique ED program, which allowed pre- or postnatal enrollment and
      did not require an initial home assessment, appears to be a safe, effective and
      flexible approach to obstetrical care.

PMID- 8753635
TI  - [Breastfeeding and factors associated with younger and older mothers].

PMID- 8753636
TI  - Measles immunization strategy: measles antibody response following MMR II
      vaccination of children at one year of age.
AB  - Measles antibody levels were determined by the plaque reduction neutralization
      (PRN) test in 580 one-year-old children before vaccination and four to six weeks
      after MMR II vaccination. Fifty-one (8.8%) had maternally derived measles
      antibody at prevaccination, and this was more common among children of women born
      before 1967 (10.6%) vs. 4.3%; p < 0.01). Among those with maternal antibody, only
      22 (43.1%) responded with a protective PRN titre of over 120, in contrast to 463
      (87.5%) of the 529 without maternal antibody at prevaccination (p < 0.0001).
      Also, the geometric mean titre was significantly lower for the former (114.1 vs.
      378.5; p < 0.0001). Overall, 15 (2.6%) of the 580 children had no antibody
      response after vaccination, and a further 80 (13.8%) had a subprotective response
      (PRN titre < 120). This lack of response could not be attributed entirely to the
      presence of maternal measles antibody at the time of vaccination. The MMR II
      vaccine may not be sufficiently immunogenic in inducing adequate measles antibody
      response after a single dose given at one year of age.

PMID- 8753637
TI  - Pediatric injuries: parental knowledge, attitudes and needs.
AB  - OBJECTIVE: To understand current parental knowledge, attitudes and information
      needs about childhood injuries. METHOD: Telephone survey of 1,516 parents in
      Metropolitan Toronto and Barrie. RESULTS: Over half of the parents knew that
      injuries were the leading cause of death and about 70% believed that injuries
      were the most preventable of major health disorders. However, most parents were
      not particularly concerned, and most had limited understanding of the major
      causes of injury. Traditional modes of receiving safety information by obtaining
      pamphlets from doctors' offices or drug stores and through media coverage were
      preferred. CONCLUSIONS: Although parents were aware of the risk of general
      childhood injury, they need to be educated about specific injury risks and
      effective countermeasures. A concerted and thoughtful effort is needed to market
      safety information for parents in Ontario.

PMID- 8753638
TI  - How safe are our schools?

PMID- 8753639
TI  - Community-based research as a tool for empowerment: the Haida Gwaii Diabetes
      Project example.
AB  - The evolution of the Haida Gwaii Diabetes Project exemplifies how community-based
      family practice research can be a tool for empowerment for both the community of
      research participants and the community based members of the research team. The
      aims of the project are to develop a better understanding of Haida beliefs about
      diabetes; to develop culturally sensitive approaches to prevention and
      management; and to attempt to apply this understanding to the development of a
      model for preventive health for native people in the province of British
      Columbia. A participatory research paradigm, coupled with explicit working
      principles by which the research team agreed to operate, addressed the concerns
      that the Aboriginal community had about the risks of research. A true working
      partnership has developed among all members of the research team, and with the
      Haida community.

PMID- 8753640
TI  - Tracking nutrition trends, 1989-1994: an update on Canadians' attitudes,
      knowledge and reported actions.
AB  - The National Institute of Nutrition tracks changes in Canadians' attitudes,
      understanding and reported actions related to nutrition issues--particularly fat
      cholesterol and fibre. Personal interviews were conducted in 1994 with a national
      sample of 1,953 adults, and the results were compared with data obtained in 1989.
      The number of people claiming that nutrition is of considerable importance in
      choosing their food has increased from 59% to 66%. More Canadians are now
      concerned about fat (82% vs 71%) and "chemicals" in foods (76% vs 68%) and more
      are planning to further reduce fat or increase fibre intake. Forty-three percent
      report having excellent or very good eating habits. The apparent use of food
      labels, lower fat/low--cholesterol products, and bran/high-fibre foods has grown
      in five years. Although awareness of nutrition terms has increased, understanding
      has changed little. The challenge is to build on consumer interest to reduce
      barriers to healthy eating through education and a supportive marketplace.

PMID- 8753641
TI  - Geographic differences in the attitudes, knowledge and infection control
      practices of Ontario dentists.
AB  - Geographic differences in the HIV related attitudes, knowledge and behaviours of
      5,997 dentists in Ontario were investigated using mailed questionnaires (response
      rate 70%). Proportionately more respondents from larger population centres
      reported that they knowingly treated HIV-infected patients (p < 0.00001), they
      were unwilling to treat HIV-infected patients (p < 0.05), they had an exaggerated
      perception of the risk of HIV infection after a needlestick injury (p < 0.01),
      they were concerned about personal risk (p < 0.01) and staff fears (p < 0.05)
      related to HIV/AIDS, and that patients with HIV or AIDS should be treated in
      hospitals/specialized practices (p < 0.001). Multiple logistic regression
      analysis controlling for age, sex, and specialty, showed that respondents who
      practised in smaller population centres were significantly more willing to treat
      HIV-infected patients ( < 10,000, odds ratio = 1.6; 10,000-49,999, odds ratio =
      1.3). Significantly fewer respondents in the Central West, and Central East
      Health Planning Region, where AIDS is most prevalent, reported that they were
      willing to treat HIV patients.

PMID- 8753642
TI  - Area variations in health behaviours.
AB  - Many studies of health inequalities use household income as an indicator of
      socioeconomic status. Because household income is usually subject to high item
      non-response rates area or census-based measures have been suggested as an
      alternative. A number of studies have shown that these are as good as or better
      than conventional measures of socioeconomic status at identifying variations in
      health status and use of health services. This paper examines the association of
      the median household income of the enumeration area in which a subject lives,
      with a variety of oral and general health behaviours. After the confounding
      effects of age and sex were controlled for, this area-based indicator was
      significantly associated with six of ten health behaviours for which data were
      collected. Four of the associations remained significant after the effects of
      house hold income were controlled for. These results suggest that area-based
      measures of socioeconomic status may have a useful role in understanding the
      influence of social contexts on health behaviours.

PMID- 8753643
TI  - Small group estimation for public health.
AB  - We used synthetic estimation and linear regression to estimate the prevalence of
      selected risk factors and health status indicators in small populations. The
      derivation was based on the sociodemographic characteristics of the populations
      and the relationships between these variables and the health variables, as
      measured by the Ontario Health Survey (OHS). The estimates were validated by a
      comparison with the direct results of the OHS (gold standards). Synthetic
      estimates were much less dispersed than the regression estimates or the direct
      OHS estimates. Regression estimates performed better than synthetic estimates on
      most validation indicators, and combined approaches performed marginally better
      yet, although there were few clear patterns. Although correlation coefficients
      with gold standards in excess of 0.8 were obtained for some variables, the
      estimates rarely met pre-determined criteria for accuracy. At present these
      techniques have limited value for public health workers, but further work is
      justified, especially on approaches combining synthetic and regression
      estimation.

PMID- 8753644
TI  - [Work and mental health: risk groups].
AB  - Analysis of the Quebec Health survey identified those Quebec industrial sectors
      and professions in which workers are at risk of higher psychological distress and
      lower psychological well-being. Risk levels were measured by odds ratio,
      controlling for: health status, sex, social support and stressful life events.
      Results show that those at risk are blue collar workers and less qualified
      workers of traditional sectors. Lower job latitude could explain those results.
      Results show that risk of mental health problems is significantly higher in the
      following industrial sectors: leather, chemicals, paint and varnish industries;
      urban bus transport and taxi; shoe, clothing and textile retail stores;
      department stores; restaurant services; insurance and public administration
      (excluding defence). Risk of mental health problems is higher in the following
      professions road transport (excluding truck drivers); textile, leather, fur
      manufacturing and repairing; housekeeping and maintenance; painters, tapestry
      workers, insulation and waterproofing, food and beverages sector; data
      processors; editors and university professors.

PMID- 8753645
TI  - Survey of malathion exposure among elevator and dock workers who handle grain.

PMID- 8753646
TI  - Evolutionary analysis of sea urchin mitochondrial tRNAs: folding of the molecules
      as suggested by the non-random occurrence of nucleotides.
AB  - Comparative analyses of the mitochondrial tRNA sequences of the sea urchins
      Arbacia lixula, Paracentrotus lividus and Strongylocentrotus purpuratus revealed
      that conserved nucleotides may be involved in determining the typical L-shaped
      spatial conformation of tRNAs. These results shed light on the specific tertiary
      interactions that allow the folding of the atypical mitochondrial tRNAs into a
      functional form. A consensus mitochondrial tRNA secondary structure was derived.
      It shows the presence of nucleotides virtually conserved only in these organisms
      that represent a sort of molecular signature in sea urchins and suggests a
      possible physiological role. Finally, we speculate that the non-canonical
      structure of animal tRNAs, as well as the deviations from the universality of the
      genetic code, may be due to the reduction in size of the metazoan mitochondrial
      genome, with the concomitant acquisition of new functions by the mitochondrial
      tRNAs.

PMID- 8753647
TI  - Analysis of exon and intron mutants in the cytochrome b mitochondrial gene of
      Saccharomyces cerevisiae.
AB  - The nucleotide changes present in a group of five cytochrome b mit- mutants were
      analyzed at the sequence level. Two single-base changes were found: one (M10-152)
      generated a nonsense codon in the first exon while the other (M8-181) created a
      missense substitution in the second exon. The other mutants all have multiple
      (three) substitutions that either resulted in a missense mutation in a coding
      region (M17-162) or else changed nucleotides in the last intron of the gene, so
      blocking its excision (M6-200 and M8-53). The synthesis of mitochondrial
      polypeptides and the steady state concentration of the complex-III subunits were
      examined. The Rieske protein and the core-4 and core-5 subunits were much reduced
      in all mutants. Consequently the overall stability of complex III is very
      sensitive even to amino-acid substitutions in the cytochrome b protein. Mutant M8
      53 provides direct evidence for the proposed role of the P9.1 stem in the core
      structure of the group-I type last intron of this gene.

PMID- 8753648
TI  - Three genes for mitochondrial proteins suppress null-mutations in both Afg3 and
      Rca1 when over-expressed.
AB  - The AFG3 gene of Saccharomyces cerevisiae encodes a mitochondrial inner membrane
      protein with ATP-dependent protease activity. To gain more insight into the
      function of this protein, multi-copy suppressors of an afg3-null mutation were
      isolated. Three genes were found that restored partial growth on non-fermentable
      carbon sources, all of which affect the biogenesis of respiratory competent
      mitochondria: PIM1(LON) encodes a matrix-localized ATP-dependent protease
      involved in the turnover of matrix proteins; OXA1(PET1402) encodes a putative
      mitochondrial inner membrane protein involved in the biogenesis of the
      respiratory chain; and MBA1 encodes a mitochondrial protein required for optimal
      respiratory growth. All three genes also suppressed a null mutation in a related
      gene, RCA1, as well as in the combination of afg3- and rca1-null.

PMID- 8753649
TI  - The unusual inheritance of multidrug-resistance factors in Saccharomyces.
AB  - The yeast PDR5 locus encodes a 160-kDa member of the ABC family of transport
      proteins. Strains bearing a deletion of this locus are drug hypersensitive.
      Resistant revertants arise when cells are plated on cycloheximide medium. About
      one-third of these are cross resistant to other agents, including oligomycin,
      fluconazole and sulfometuron methyl. Most of the revertants exhibit linkage to
      the PDR5 locus and map in three locations. Curiously, the multi-drug resistance
      is not due to a single mutation. Most of the revertants behave as though they
      contained several tightly linked resistance factors.

PMID- 8753650
TI  - Natural translocation of a large segment of chromosome III to chromosome I in a
      laboratory strain of Saccharomyces cerevisiae.
AB  - We have investigated chromosomal segregation during meiosis in a cross between
      two polymorphic haploid laboratory strains of Saccharomyces cerevisiae, FL100 and
      GRF18. These two strains have large chromosome-length polymorphisms for
      chromosomes I and III allowing for easy scoring of parental chromosomes after
      meiotic segregation. Chromosome III in the FL100 strain was 35 kb shorter than
      chromosome III in GRF18, while FL100 chromosome I was 40 kb larger than
      chromosome I in GRF18. Segregation analysis of chromosomes I and III in 50
      tetrads showed an apparent association between chromosomes I and III, whereas
      only the original parental association of chromosomes I and III was found in the
      spores. By hybridization with chromosome-specific probes we have shown that the
      polymorphisms are due to a large translocation from chromosome III onto
      chromosome I in FL100. The translocated fragment is larger than 80 kb and was
      mapped between Ty and HML. In nine tetrads analyzed, chromosome-length
      polymorphisms which did not segregate according to Mendelian law were observed.

PMID- 8753651
TI  - The mus-8 gene of Neurospora crassa encodes a structural and functional homolog
      of the Rad6 protein of Saccharomyces cerevisiae.
AB  - We cloned a DNA repair gene, mus-8, of Neurospora crassa and sequenced the
      genomic DNA and cDNA. Nucleotide-sequence analysis indicated that the mus-8 gene
      contains an open reading frame (ORF) of 456 bp, interrupted by three small
      introns. The deduced amino-acid sequence showed that the mus-8 gene encodes a 17
      kDa protein which has 77.5% and 83.3% identity to the Rad6 protein of
      Saccharomyces cerevisiae and the rhp6(+) protein of Schizosaccharomyces pombe,
      respectively. The Rad6 protein is a ubiquitin-conjugating enzyme (E2) and is
      required for DNA repair, mutagenesis, and sporulation in yeast. Introduction of
      the mus-8 gene into a S. cerevisiae rad6 mutant resulted in significant recovery
      of DNA repair functions, especially UV-mutagenesis, and also sporulation, both of
      which are defective in the rad6 mutant. It is therefore postulated that mus-8 of
      Neurospora has a function very similar to that demonstrated for RAD6 of S.
      cerevisiae.

PMID- 8753652
TI  - The isoprenoid pathway: cloning and characterization of fungal FPPS genes.
AB  - Farnesylpyrophosphate synthase (FPPS) is a key enzyme in isoprenoid biosynthesis.
      Several classes of essential metabolites, including sterols, quinones,
      carotenoids and gibberellins, are terpenoids with high biological activity. The
      structural gene for FPP synthase was isolated from two ascomycete fungi,
      Neurospora crassa and Gibberella fujikuroi. A comparative analysis of the
      nucleotide sequences of both FPPS genes revealed the presence of introns at the
      same positions at the 5' end of the coding regions. Furthermore, the most
      conserved region of the gene was isolated from two other plant pathogenic fungi,
      Sphaceloma manihoticola and Claviceps purpurea, by PCR. Sequence analysis showed
      a high degree of similarity between the deduced proteins of all known FPP
      synthase genes. In contrast to animals, all analyzed fungi contain a single copy
      of the gene, although FPP is the precursor for essential sterol and quinone
      biosynthesis and secondary metabolites, such as gibberellins, as well.
      Transcription analysis in different light regimes has shown that the FPPS genes
      in G. fujikuroi and N. crassa are not regulated by light induction.

PMID- 8753653
TI  - Expression of the Sclerotinia sclerotiorum polygalacturonase pg1 gene: possible
      involvement of CREA in glucose catabolite repression.
AB  - Northern-blot analysis of RNA isolated from Sclerotinia sclerotiorum grown on
      either glucose or polygalacturonate as the sole carbon source showed that pg1,
      encoding a neutral polygalacturonase, was not expressed during growth in both
      media. In contrast, transcripts of this gene were detected during infection of
      sunflower germlings. Analysis of the promoter sequence revealed a number of cis
      acting sequences known to regulate the expression of many fungal promoters.
      Protein-DNA-binding experiments showed that proteins extracted from mycelia grown
      on polygalacturonate or glucose interacted with different regions of the
      promoter. The GST-CREA fusion protein, containing the two zinc fingers of the
      Aspergillus nidulans repressor CREA involved in carbon catabolite repression,
      forms several complexes with DNA fragments carrying the consensus 5'-SYGGRG-3'.
      These results suggest that a CREA homolog may be involved in the regulation of
      pg1.

PMID- 8753654
TI  - Co-expression of a Phanerochaete chrysosporium cellobiohydrolase gene and a
      Butyrivibrio fibrisolvens endo-beta-1,4-glucanase gene in Saccharomyces
      cerevisiae.
AB  - A cDNA fragment encoding the Phanerochaete chrysosporium cellobiohydrolase (cbh1
      4) was amplified and cloned with the aid of the polymerase chain reaction (PCR)
      technique. The cbh1-4 gene and the Butyrivibrio fibrisolvens endo-beta-1,4
      glucanase (end1) gene were successfully expressed in Saccharomyces cerevisiae
      under the control of the phosphoglycerate kinase-I (PGK1) and alcohol
      dehydrogenase-II (ADH2) gene promoters and terminators, respectively. The native
      P. chrysosporium signal sequence mediated secretion of cellobiohydrolase in S.
      cerevisiae, whereas secretion of the endo-beta-1,4-glucanase was directed by the
      signal sequence of the yeast mating pheromone alpha-factor (MFalpha1S). These
      constructs, designated CBH1 and END1, respectively, were expressed separately and
      jointly in S. cerevisiae. The construction of fur1 ura3 S. cerevisiae strains
      allowed for the autoselection of these multicopy URA3-based plasmids in rich
      medium. Enzyme assays confirmed that co-expression of CBH1 and END1
      synergistically enhanced cellulose degradation by S. cerevisiae.

PMID- 8753655
TI  - Successful crosses and molecular tetrad and progeny analyses demonstrate
      heterothallism in Mycosphaerella graminicola.
AB  - Monospore isolates of Mycosphaerella graminicola considered to originate from one
      ascus were analysed by the polymerase chain reaction (PCR) with 32 RAPD primers.
      Eighteen of these revealed three classes of polymorphisms, which enabled a RAPD
      based tetrad analysis. Four pairs of isolates resulting from a single diploid
      nucleus were determined. A procedure to cross these isolates was developed to
      investigate the mating system. Three of six crosses were successful, and the
      segregation of mating types in accordance with the tetrad analysis strongly
      points to a bipolar heterothallic mating system in M. graminicola. Random
      ascospore progenies from the successful crosses, each comprising 54 isolates,
      were studied with three primers to determine the mode of inheritance of the RAPD
      markers. Mendelian segregation and recombination of RAPD markers was observed in
      all progenies.

PMID- 8753656
TI  - Hairpins create minute inversions in non-coding regions of chloroplast DNA.
AB  - Minute inversions (4 bp in length), associated with probable hairpin secondary
      structures, were inferred from comparative analysis of rpl16 intron sequences
      from the chloroplast genomes of Chusquea species and related bamboos (Poaceae).
      The inverted sequences, which appear to have arisen independently on several
      occasions, comprise entire loops of the putative hairpins. The process of
      inversion seems dependent upon the stem length of the hairpin and its estimated
      free energy of formation. A similar inversion was uncovered for other plants in a
      previously published data set for a different non-coding region of the
      chloroplast genome, suggesting that the inversional process may be a common
      feature of non-coding DNA evolution. Several implications for phylogenetic
      analysis are noted.

PMID- 8753657
TI  - Rearrangements at a DNA-fingerprint locus in the rice blast fungus.
AB  - Populations of the rice blast fungus, Magnaporthe grisea, can be sorted into
      clonal lineages based on restriction fragment length polymorphisms (RFLPs)
      detected with the repetitive DNA sequence MGR586. Mechanisms that produce DNA
      fingerprint variation among lineages, are not known. In the process of analyzing
      the meiotic segregation of MGR586 RFLPs we identified a novel polymorphism,
      called MGR586-P2, in one member of a sister-spore pair from a complete tetrad.
      Molecular cloning revealed that P2 was generated by a nearby insertion of a
      novel, long-terminal-repeat (LTR)-containing retrotransposon. Genetic analysis
      showed that P2 and its progenitor polymorphism (P1) are alleles of a single
      polymorphic locus termed MGR586-PL (PL). Surprisingly, we found that a strain
      harboring PL recurrently produced clonal descendants harboring P1, P2 and
      possibly a third allele designated P3. PL is not located near a telomeric region.
      Our results show that some DNA-fingerprint loci may be hypervariable and undergo
      recurrent rearrangements. These findings have implications for interpreting DNA
      fingerprint profiles from M. grisea populations.

PMID- 8753658
TI  - Safe use of power injectors with central and peripheral venous access devices for
      pediatric CT.
AB  - PURPOSE: We report our experience in the safe use of power injectors with central
      and small-gauge peripheral venous access devices for intravenous administration
      of contrast agent to children undergoing computed tomography (CT) examinations.
      MATERIALS AND METHODS: We reviewed the medical records of 500 patients randomly
      selected from the 3121 children who underwent intravenous contrast-enhanced CT
      examinations at our institution from November 1993 through July 1995. RESULTS:
      The group of 500 patients, all younger than 18 years of age, accounts for 16 % of
      the contrast-enhanced CT examinations performed during the study period. Medrad
      MCT 311 Mark V or Medrad MCT Plus 311 power injectors were used to intravenously
      administer Omnipaque 300 (2 ml/kg, maximum dose = 150 ml) through venous access
      devices. These devices comprised Hickman or Broviac lines (n = 228), subcutaneous
      Port-A-Caths (n = 55), small-gauge butterfly needles (n = 215), and percutaneous
      intravenous central lines (n = 2). Two complications, one involving a Hickman
      line and the other a subcutaneous Port-A-Cath, occurred in the study population.
      These complications correspond to a frequency of 0.4 %. Six cases of contrast
      extravasation, all of them with the use of 23- (n = 1) and 25-gauge (n = 5)
      butterfly catheters (frequency = 0.2 %), occurred among the remaining 2621 cases.
      CONCLUSION: In light of the low frequency of complications, power injectors and
      central venous access devices or small-gauge butterfly catheters are safe systems
      for delivery of intravenous contrast material to pediatric patients. We feel that
      our strict adherence to manufacturers' guidelines and previously reported
      techniques partially accounts for our success with these modes of delivery.

PMID- 8753659
TI  - Pediatric hepatic CT: an injection protocol.
AB  - OBJECTIVE: To determine an injection protocol for pediatric hepatic CT and to
      investigate the use of power injection. MATERIALS AND METHODS: Eighty-seven
      studies were prospectively performed using ioversol (320 mg iodine per cc) at 2
      cc/kg. Three techniques were used: helical (1 s/slice); dynamic, non-breath-hold
      (5.5 s/slice); dynamic, breath-hold (10 s/slice) scans. The liver-scan time for
      each study was determined. Scan initiation ranged from 25 to 80 s. An injection
      duration (50-100 seconds) was selected. From the contrast volume (2 cc/kg x kg
      body wt) and injection duration, the injection rate (cc/s) was calculated for
      each patient. Each study was grouped by injection rate corrected for body weight
      (cc/kg/min) into: 1.2-1.5, 1.51-2.0, and 2.01-2.4. The aortic/liver attenuation
      curves were plotted for each group. RESULTS: Liver-scan time for helical studies
      was a mean of 26 s, for dynamic, non-breath-hold studies 75 s, dynamic breath
      hold scans were 154 s. Injection rates of 1.2-1.5 cc/kg/min produced a scanning
      interval of 165 s. Injection rates of 1.51-2.0 cc/kg/min produced a scanning
      interval of 120 s. Injection rates of 2.01-2.4 cc/kg/min produced a scanning
      interval of 90 s. There was no increase in hepatic attenuation for the injection
      rates 2.01-2.4 cc/kg/min compared with 1.51-2.0 cc/kg/min. There was one
      complication related to injection through a central line. CONCLUSIONS: An
      injection protocol was determined for helical studies with injection rates of 1.7
      2.0 cc/kg/min with initiation at 60 s; for dynamic, non-breath-hold studies with
      injection rates of 1.5-1.7 cc/kg/min with initiation at 50 s; and for dynamic
      breath-hold studies with injection rates of 1.2-1.5 cc/kg/min with initiation at
      45 s. Power injection was used safely in our population.

PMID- 8753660
TI  - The lungs in immature infants: how important is surfactant therapy in preventing
      chronic lung problems?
AB  - Seventy-five premature infants weighing between 600 and 3200 g were studied over
      a period of 1 year. All of the infants received surfactant therapy for hyaline
      membrane disease immediately after birth and, thereafter, up to four doses every
      6 h. The roentgenographic findings in all patients were documented at birth and
      at 2 days, 7-10 days, and 21-28 days of life. Larger babies responded to
      surfactant therapy better than did smaller infants. The smaller infants, even
      after initial clearing, were prone to develop pulmonary edema and the bubbly
      lungs of bronchopulmonary dysplasia. These data suggest that small infants, while
      initially responding to surfactant therapy with clearing of their lungs, are
      still at considerable risk of developing chronic lung disease in the form of
      pulmonary edema and bronchopulmonary dysplasia. An explanation is offered for why
      this occurs; at the same time it is suggested that, in view of our findings and
      those in the literature, the problems of pulmonary edema and bubbly lungs be more
      clearly separated.

PMID- 8753661
TI  - The various types of anorectal fistula in male imperforate anus.
AB  - The purpose of this paper is to provide a review of the anorectal fistulas
      occurring in male imperforate anus, with a suggested classification based on the
      site of termination of the fistula, namely, the bladder, the urethra, and the
      perineum. The fistulas included in these categories are discussed in some detail,
      with reference to previous cases or descriptions in the literature and with some
      personal observations.

PMID- 8753663
TI  - MRI and radiographic findings in Currarino's triad.
AB  - Currarino's triad is a rare complex of a congenital sacral bony abnormality,
      anorectal malformation and a presacral mass. Intractable constipation since birth
      is the leading symptom of this triad, which follows an autosomal dominant mode of
      heredity. We report conventional radiographic and MR findings in one family
      consisting of a mother and her two daughters. In all three cases, radiography
      revealed an abnormality of the os sacrum, the so-called scimitar sacrum. MR
      examination, undertaken next in our institution, was applied with T1-, T2- and
      proton density weighted sequences in all three orientations before and after i.
      v. application of gadolinium diethylene-triamine-pentaacetic acid (Gd-DTPA). In
      two patients we were able to diagnose the complete form of the triad and in one
      patient an incomplete form. In any case of a radiographically diagnosed scimitar
      sacrum in combination with constipation, Currarino's triad should be considered.
      MRI, as the method of choice, should be the next step to detect a presacral mass
      and any anomalies of the spinal canal. The importance of early recognition lies
      in the high morbidity and mortality rates resulting from this disorder.

PMID- 8753664
TI  - Hydrocele of the spermatic cord: embryology and ultrasonographic appearance.
AB  - Five cases of hydrocele of the spermatic cord are presented. All five patients
      had a firm inguinal mass, and ultrasonography, performed to exclude adenopathy,
      incarcerated hernia, and paratesticular tumor, showed an avascular cystic mass
      superior to and separate from the testicle. A testicular hydrocele did not
      coexist. This typical appearance should lead to a confident diagnosis of this
      benign but rare anomaly. Elective surgery may prevent the development of an
      acquired indirect hernia.

PMID- 8753665
TI  - Malrotation discovered during routine radionuclide gastric emptying study.
AB  - In infants with recurrent vomiting, and especially bilious vomiting, the
      algorithmic approach is to perform conventional barium upper gastrointestinal
      radiography to rule out malrotation and midgut volvulus, which are surgical
      emergencies. However, children with protracted vomiting and failure to thrive are
      candidates for medical treatment. These children are often evaluated by
      radionuclide gastric emptying studies to assess gastric emptying. Three patients
      are presented in whom the radionuclide gastric emptying study revealed the
      presence of a malrotation anomaly which had been undetected by antecedent barium
      gastrointestinal radiographic studies.

PMID- 8753666
TI  - Left paraduodenal hernia leading to ileal obstruction.
AB  - Left paraduodenal hernias are a rare cause of abdominal pain or obstruction.
      However, because there is high associated mortality (20 %), prompt and accurate
      diagnosis is essential. Because internal hernias are not detectable on physical
      examination, imaging is relied upon for pre-operative diagnosis. Although both
      computed tomography and barium studies demonstrate left paraduodenal hernias as a
      cluster of bowel located posterior to the stomach and to the left of the distal
      duodenum with absence of the normal interdigitation between loops, the findings
      may be subtle. Knowledge of these findings can avoid an unnecessary delay in
      diagnosis. We present the case of a 15-year-old girl with a left paraduodenal
      hernia, where initial CT and barium studies demonstrated nonobstructed jejunum
      within the hernia sac. Two weeks later a repeat study showed obstructed distal
      ileum, rather than proximal jejunum, within the sac.

PMID- 8753667
TI  - Radiation-induced meningioma in children: report of two cases and review of the
      literature.
AB  - Meningioma developed in two children who had received high-dose cranial radiation
      for malignant brain tumors. Meningioma as a radiation-induced neoplasm has
      received little notice in the radiologic literature. Thirty-three cases have been
      reported since 1953, primarily in the neurosurgical literature. The current cases
      differ from those previously reported in having a much shorter latency period
      between irradiation and the development of meningioma.

PMID- 8753668
TI  - Tuberculous meningitis in native Dutch children: a report of four cases.
AB  - Although it is believed that in the western countries tuberculosis is a disease
      confined to high-risk groups such as immigrants, we describe four cases of
      tuberculous meningitis (TBM) in native Dutch children. The inverse relation
      between the delay in starting therapy and the clinical outcome makes early
      diagnosis of TBM essential. The often non-specific presenting symptoms and
      laboratory results, the time-consuming character of cultures and the
      unfamiliarity of western medical staff with the disease all may contribute to a
      delay in diagnosis of TBM. We believe that especially gadolinium-enhanced MRI or
      contrast-enhanced CT can be very helpful in the early diagnosis. Although not
      specific, hydrocephalus and basal meningeal enhancement on MRI or CT, together
      with the clinical suspicion can suggest the diagnosis to such an extent that
      there is enough reason to start antituberculous treatment.

PMID- 8753669
TI  - Growth of the solitary kidney after nephrectomy in children with unilateral
      Wilms' tumor.
AB  - OBJECTIVE: We reviewed the length of the solitary kidney from all ultrasound
      examinations in 34 children who had undergone unilateral nephrectomy for Wilms'
      tumor, in order to determine the frequency of renal hypertrophy in this
      population. Standard sonographic criteria for nephromegaly were used. MATERIALS
      AND METHODS: We generated a z-score for each measurement of the renal length,
      using an interpolated computer model based on published standards for sonographic
      renal length in relation to age. A retrospective age- and gender-matched control
      population of children with sonographically normal paired kidneys was generated
      from a departmental computerized pediatric uroradiology data base, and their
      ipsilateral renal lengths were compared with those of the study patients.
      Sonographic renal hypertrophy (SRH) was defined by two or more consecutive
      measurements of the renal length exceeding two standard deviations longer than
      the mean for the patient's age, with no later normal measurement. RESULTS:
      Seventeen (50 %) of the 34 patients developed SRH. The latest measurements of the
      solitary kidney in the patients were significantly longer (mean z = 2.210) than
      in their controls (mean z = 0.040), even among the patients who did not develop
      SRH (patients' mean z = 1.000, controls' mean z = -0. 210, p < 0.001). Because
      boys had slightly longer kidneys than girls (both patients and controls), SRH was
      also noted more often in boys. The frequency of SRH was unrelated to age at
      nephrectomy, side of the solitary kidney, tumor stage, chemotherapy regimen, or
      treatment with radiation therapy. CONCLUSIONS: Although renal growth in a
      solitary kidney is accelerated in most children after unilateral nephrectomy for
      Wilms' tumor, the sonographic length of the solitary kidney will be larger than
      normal in only half of the patients.

PMID- 8753670
TI  - Sonographic measurement of renal length in children: does the position of the
      patient matter?
AB  - PURPOSE: This prospective study was designed to determine the effect of patient
      positioning on sonographic measurements of renal length in children. Materials
      and methods. Two dedicated pediatric ultrasonographers (observers A and B)
      measured the sonographic lengths of 48 kidneys in 25 children (two had unilateral
      renal agenesis). Each observer obtained the two "longest possible" measurements
      for each kidney with the patient in three positions: supine, contralateral
      decubitus, and prone. Patients with myelomeningocele, hydronephrosis, and renal
      cysts were excluded. RESULTS: Both examiners obtained significantly higher values
      for renal lengths with the children lying supine (observer A P </= 0.0017;
      observer B P </= 0.0409) or in contralateral decubitus (observer A P </= 0.0001;
      observer B P </= 0.0419) than with them lying prone. There was no significant
      difference between the supine and decubitus measurements. The mean difference
      between the supine and prone measurements for the observers was 3.0 mm for
      observer A and 1.8 mm for observer B. The mean difference between the
      contralateral decubitus and prone measurements was 3.0 mm for observer A and 1.6
      mm for observer B. CONCLUSION: Sonographic measurements of renal length made with
      the patient lying supine or in contralateral decubitus yield slightly higher
      values than those made with the patient prone.

PMID- 8753671
TI  - Mental retardation - megaepiphyses - ulnar pseudoepiphyses - hypoplastic fibulae 
      brachymesophalangia: a new syndrome.
AB  - The distinctive radiographic features - megaepiphyses, hypoplastic fibulae, ulnar
      pseudoepiphyses and brachymesophalangy - in a 14-year-old Japanese boy with
      mental retardation are reported.

PMID- 8753672
TI  - Pneumothorax as the presenting sign of Pneumocystis carinii infection in an HIV
      positive child with prior lymphocytic interstitial pneumonitis.
AB  - An HIV-positive child presented with a pneumothorax secondary to cavitary
      Pneumocystis carinii pneumonia (PCP). Lymphocytic interstitial pneumonitis had
      been evident on earlier radiographs but had resolved, concurrent with a decrease
      in her CD4 counts, before the radiographic changes of PCP became evident. As
      immune function declines in HIV-positive children, the chest radiograph may
      paradoxically clear. In such a setting, development of focal lung disease,
      including pneumothorax, may herald Pneumocystis carinii infection.

PMID- 8753674
TI  - Proportional anatomical stereotactic atlas for visual interpretation of brain
      SPET perfusion images.
AB  - A semi-automatic method was developed to determine the anterior (AC) and
      posterior (PC) commissures on brain single-photon emission tomographic (SPET)
      perfusion images, and then to draw the proportional anatomical Talairach's grid
      on each axial SPET image. First, the AC-PC line was defined on SPET images from
      the linear regression of four internal landmarks (frontal pole of the brain,
      inferior limit of the anterior corpus callosum, sub-thalamic point and occipital
      pole). Second, the SPET position of AC and PC points on the AC-PC line was
      automatically determined from measurements made on hard copies of magnetic
      resonance (MR) images of the patients. Finally, a proportional Talairach's grid
      was automatically drawn on each axial SPET image. To assess the accuracy of
      localization of AC and PC points, co-registered technetium-99m
      hexamethylpropylene amine oxime SPET and MR images from 11 subjects were used.
      The mean displacements between estimated points on SPET and true points on MRI
      (Deltax=sagittal, Deltay=frontal and Deltaz=axial displacement) were calculated.
      The mean displacements (in mm) were Deltax=-1.4+/-1.8, Deltay=-1.7+/-3.3 and
      Deltaz=-1. 1+/-2.5 for AC, and Deltax=-1.8+/-1.8, Deltay=0.3+/-3.2 and Deltaz=
      1.3+/-2.7 for PC. These displacements represented an error of less than 5 mm at
      the anterior or posterior pole of the brain or at the vertex. Intra- and inter
      observer comparisons did not reveal significant differences in mean
      displacements. Thus, this semi-automatic method results in reproducible and
      accurate stereotactic localization of SPET perfusion abnormalities. This method
      can be used routinely for repeat follow-up studies in the same subject as well as
      in different individuals without requiring SPET-MRI co-registration.

PMID- 8753673
TI  - Radioligands for brain 5-HT2 receptor imaging in vivo: why do we need them?

PMID- 8753676
TI  - Quantitative evaluation of neutral amino acid transport in cerebral gliomas using
      positron emission tomography and fluorine-18 fluorophenylalanine.
AB  - To elucidate the mechanism of large neutral amino acid (LNAA) transport in
      cerebral gliomas and to evaluate the clinical usefulness of positron emission
      tomography (PET) with fluorine-18 fluorophenylalanine (18F-Phe), we examined 18
      patients with cerebral glioma using dynamic PET and 18F-Phe. By employing two
      compartment model analysis, the influx rate K1, the efflux rate k2 and the
      distribution volume (Vd) of 18F-Phe were estimated in tumour tissue and
      contralateral normal grey matter. 18F-Phe showed increased accumulation in tumour
      tissue regardless of the grade of malignancy in all patients. The rate of uptake
      of 18F-Phe in high-grade glioma was significantly higher than in low-grade glioma
      (P <0.05). However, it was difficult to evaluate the tumour grade only from the
      18F-Phe accumulation in individual cases. Values of K1 and Vd were significantly
      increased in the tumour tissue. The K1 value of the tumour tissue tended to
      decrease with increasing LNAA concentration in plasma. Therefore, influx of 18F
      Phe into tumour tissue is mainly related to the carrier-mediated active
      transport. It is concluded that PET with 18F-Phe is of clinical value for tumour
      detection rather than assessment of tumour malignancy.

PMID- 8753675
TI  - Changes in local cerebral blood flow by neuroactivation and vasoactivation in
      patients with impaired cognitive function.
AB  - Imaging of local cerebral blood flow (lCBF) may serve as an important
      supplementary tool in the aetiological assessment of dementias. In early or
      preclinical disease, however, there are less characteristic changes in lCBF. In
      the present study it was investigated whether vasoactivation or neuroactivation
      may produce more pronounced local lCBF deficits. Local CBF was investigated by
      using technetium-99m hexamethylpropylene amine oxime and single-photon emission
      tomography (SPET) in 80 patients (50 with mild cognitive impairment and 30 with
      dementia of Alzheimer type (DAT), all without evidence of cerebrovascular
      disease) at rest (baseline) and during activation. In 31 studies patients
      underwent vasomotor activation with acetazolamide, while 62 studies were
      performed under cognitive challenge (neuroactivation by labyrinth task). Cortical
      activity relative to that of cerebellum increased significantly in a right
      temporal region and tended to increase in other cortical regions upon
      vasoactivation. In contrast, neuroactivation reduced cortical activity relative
      to that of cerebellum in several left and right temporal and in left parietal
      regions. Visual classification of SPET images of patients with probable DAT by
      three observers resulted in a reduction of the number of definitely abnormal
      patterns from 9/12 to 4/12 by vasoactivation and an increase from 10/18 to 15/18
      by neuroactivation. Correspondingly, abnormal ratings in patients with mild
      cognitive dysfunction were reduced from 7/19 to 5/19 by vasoactivation and were
      increased from 12/21 to 18/21 by neuroactivation. In conclusion, vasoactivation
      does not enhance local relative perfusion deficits in patients with cognitive
      impairment of non-vascular aetiology, whereas neuroactivation by labyrinth task
      produces more pronounced local flow differences and enhances abnormal patterns in
      lCBF imaging.

PMID- 8753677
TI  - Myocardial infarction in rats: high-resolution single-photon emission tomographic
      imaging with a pinhole collimator.
AB  - The purpose of this study was to evaluate the accuracy of myocardial imaging by
      means of high-resolution single-photon emission tomography (SPET) with a pinhole
      collimator in rats with experimental infarction. Myocardial infarctions were
      induced in male Wistar rats by ligation of the left coronary artery for 30 min,
      followed by reperfusion. Two days after the reperfusion, pinhole SPET was
      performed after the intravenous administration of 111 MBq of thallium-201
      chloride, using a rotating gamma camera equipped with a pinhole insert (2.0-mm
      aperture) in a low-energy pinhole collimator. SPET projection data were collected
      at 6 degrees increments over 360 degrees using a 4-cm radius of rotation to
      reconstruct the short- and long-axis images. Projection data were acquired in 15
      or 30 s, the SPET imaging being accomplished within 40 min after the injection of
      201Tl. After SPET, the rats were sacrificed to remove the hearts for
      autoradiography (ARG) and nitroblue tetrazolium (NBT) staining as a visual
      correlative study. Quantitative correlative studies between pinhole SPET and ARG
      were performed with linear regression analysis for infarct size and distribution
      properties (relative counts on SPET images and relative density on
      autoradiographs) on the short-axis sections. All infarcts (4 mm in minimum
      diameter) in seven rats were detected by pinhole SPET. The SPET images in rats
      with or without myocardial infarction were consistent with the findings of ARG
      and NBT staining. There were significant correlations between pinhole SPET and
      ARG with respect to the infarct size (r=0.933, P <0.001; n=15) and the relative
      radiotracer distribution (r=0.931, P <0.001; n=68). This study therefore
      confirmed the accuracy of myocardial pinhole SPET imaging in rats with myocardial
      infarction. This method may partially substitute for ARG and prove useful for
      assessing new myocardial imaging agents in vivo in small laboratory animals.

PMID- 8753678
TI  - Cardiac iodine-123 metaiodobenzylguanidine uptake in animals with diabetes
      mellitus and/or hypertension.
AB  - The aim of the present study was to evaluate the use of the noradrenaline
      analogue iodine-123 metaiodobenzylguanidine ([123I]MIBG) for the assessment of
      cardiac sympathetic activity in the presence of diabetes mellitus and/or
      hypertension in animal models. One model used Wistar-Kyoto rats (WKY) and
      spontaneously hypertensive rats (SHR) rendered diabetic at 12 weeks of age by an
      intravenous injection of streptozotocin (STZ). The other model used lean and
      obese Zucker rats. In all groups basic haemodynamic values were established and
      animals received an intravenous injection of 50 microCi [123I]MIBG. Initial
      myocardial uptake and wash-out rates of [123I]MIBG were measured
      scintigraphically during 4 h. After sacrifice, plasma noradrenaline and left
      cardiac ventricular beta-adrenoceptor density was determined. The diabetic state,
      both in STZ-treated rats (direct induction) and in obese Zucker rats (genetic
      induction), appeared to induce a lower cardiac density of beta-adrenoceptors,
      indicative of increased sympathetic activity. Cardiac [123I]MIBG then showed
      increased wash-outs, thereby confirming enhanced noradrenergic activity. This
      parallism of results led to the conclusion that [123I]MIBG wash-out measurements
      could provide an excellent tool to assess cardiac sympathetic activity non
      invasively. However, in hypertension (WKY vs SHR), both parameters failed to show
      parallelism: no changes in beta-adrenoceptor density were found, whereas
      [123I]MIBG wash-out rate was increased. Thus, either [123I]MIBG washout or beta
      adrenoceptor density may not be a reliable parameter under all circumstances to
      detect changes in the release of noradrenaline. Changes in the initial uptake of
      [123I]MIBG were observed as well. This may be a good marker for the disappearance
      of cardiac innervation, but it seems not to be a good parameter for
      distinguishing between loss of sympathetic innervation and enhanced uptake of
      noradrenaline in pathological conditions.

PMID- 8753679
TI  - Regional myocardial motion and thickening assessed at rest by ECG-gated 99mTc
      MIBI emission tomography and by magnetic resonance imaging.
AB  - We have validated ECG-gated emission tomography using technetium-99m
      methoxyisobutylisonitrile for the assessment of regional ventricular function by
      comparing it with cine magnetic resonance imaging (MRI). Gated tomography was
      performed at rest in 24 patients referred for myocardial perfusion imaging [17
      males and seven females with a mean age of 58 years, nine of whom had had a
      previous myocardial infarction (MI)]. Scores were assigned to each of nine
      myocardial segments for wall motion and for thickening. Cine MRI was analysed in
      an identical fashion. Four out of 216 (2%) segments were uninterpretable by gated
      tomography because of inadequate tracer uptake. In eight patients without
      coronary artery disease (CAD), wall motion and thickening were normal by both
      methods. Gated tomography showed abnormal wall motion or thickening in all
      patients with previous MI and in five of seven patients with CAD but no prior MI.
      Association between wall motion and thickening was good (rs=0. 86). Overall,
      there was good agreement between gated tomography and MRI for both wall motion
      (178/212 segments, kappa=0.66) and wall thickening (184/212 segments,
      kappa=0.69). In segments with severely reduced perfusion, however, there was
      poorer agreement (kappa=0.31). Interobserver and intraobserver agreement was high
      (kappa from 0.61 to 0.78). Thus, in patients investigated for CAD, there is good
      overall agreement between gated tomography and MRI but the agreement is lower in
      segments with severe perfusion defects.

PMID- 8753680
TI  - Recovery of impaired left ventricular function in patients with acute myocardial
      infarction is predicted by the discordance in defect size on 123I-BMIPP and 201Tl
      SPET images.
AB  - A discrepancy between myocardial perfusion defect and wall motion abnormalities
      is frequently found early after coronary reperfusion in patients with acute
      myocardial infarction. The purpose of this study was to assess recovery of
      impaired left ventricular function by reference to the discordance in defect size
      between myocardial fatty acid uptake and myocardial perfusion using combined
      single-photon emission tomographic (SPET) imaging early after coronary perfusion
      therapy. In 37 patients with acute myocardial infarction, iodine-123 15-(p
      iodophenyl)-3(R, S)-methylpentadecanoic acid (BMIPP) and thallium-201 SPET scans
      were performed early after coronary reperfusion. A severity score was determined
      from the extent of the imaging defect with each tracer. Left ventricular wall
      motion score (WMS) and ejection fraction (EF) were obtained at admission and at 4
      weeks after the onset of infarction. In 32 of the 37 patients, discordance in
      defect sizes delineated with the two SPET studies was found during the acute
      stage. The severity score for BMIPP was larger than that for 201Tl during the
      acute stage (7. 7+/-2.4 vs 4.4+/-2.5, P <0.001). There was a fair correlation
      between the severity score for BMIPP and WMS (r=0.82, P <0.0001), but a poor
      correlation between that for 201Tl and WMS. The extent of discordance in severity
      scores between BMIPP and 201Tl during the acute stage correlated well with the
      extent of the improvement in WMS (r=0.86, P <0.0001) and that of EF (r=0.85, P
      <0.0001). We conclude that the discordance in defect size on BMIPP and 201Tl SPET
      images during the acute stage of infarction is an early predictor of the
      viability of the myocardium at risk of infarction.

PMID- 8753681
TI  - On the generation of short-axis and radial long-axis slices in thallium-201
      myocardial perfusion single-photon emission tomography.
AB  - We tried to develop fully automatic reorientation algorithms in thallium-201
      myocardial perfusion single-photon emission tomography, and tested a method to
      evaluate the quality of reorientation. The left ventricle was automatically
      segmented using count density information, contours generated with Laplacian
      operators in both transaxial and sagittal slices, and morphological and
      positional characteristics of the contours. Reorientation was automatically
      performed based on knowledge of the long axis of a second degree surfac fitted to
      the myocardial wall. We tried to achieve improvement in reorientation without
      relying on any functional description of left ventricular shape. Quality of
      reorientation was evaluated and improved using interactive tools in combination
      with radial long-axis slices. Two groups of 50 patients, after stress and rest,
      were analysed using the traditional manual and the fully automatic procedures.
      Automatic segmentation was successful in 98 out of 100 cases, and automatic
      reorientation was of reasonable quality. Reorientation obtained with the radial
      long-axis slices tool was better than after traditional manual or automatic
      reorientation. Automatic reorientation based on second degree surface fitting was
      in our hands less successful than reported in the literature. The tool using
      radial long-axis slices provides a better standard for testing reorientation
      algorithms than the traditional manual method.

PMID- 8753682
TI  - Scintimammography with technetium-99m tetrofosmin in the diagnosis of breast
      cancer and lymph node metastases.
AB  - The aim of the study was to evaluate the possible role of scintimammography (SMM)
      with technetium-99m tetrofosmin in breast cancer. Thirty-three patients with
      breast disease and ten normal controls were included in the study. Planar
      scintigraphic images in supine anterior, prone lateral and lateral views, with
      the patient lying in lateral recumbency, were acquired. A qualitative analysis
      evaluating both breasts and lymph nodes was performed. All breast lesions were
      verified after surgery and/or by fine-needle aspiration. In 8 of the 33 patients,
      mammography was inconclusive because of mastectomy or dense breasts. For
      mammography, a sensitivity of 95.6%, a specificity of 66.7% and an accuracy of
      89.6% were obtained. At SMM, 26 out of 28 malignant lesions (average size 2.8 cm,
      range 0. 4-12 cm), including two recurrences, were detected with a 92.8%
      sensitivity, a 100% specificity and a 95.1% accuracy. The smallest detectable
      carcinoma measured 0.6 cm. Two false-negative results on SMM were found in a 0.4
      cm intraductal carcinoma and in the only mucinous papillary carcinoma in our
      series. With regard to lymph node analysis, 11 out of 12 axillary metastases
      (sensitivity=91.6%) were detected. A false-positive result, yielding a
      specificity of 92. 3% was also obtained. A metastatic involvement of the internal
      mammary chain was observed. No uptake was seen in 11 benign mammary lesions or at
      the level of the breast and axilla when neoplastic involvement was absent. In
      conclusion, SMM with 99mTc-tetrofosmin is an effective technique for the
      evaluation of primary breast carcinomas, recurrences and lymph node metastases.

PMID- 8753683
TI  - Scintimammography with technetium-99m methoxyisobutylisonitrile: comparison with
      mammography and magnetic resonance imaging.
AB  - The aim of the study was to compare the diagnostic accuracy of scintimammography
      with technetium-99m methoxyisobutylisonitrile (MIBI; SMM) in the detection of
      primary breast cancer with that of mammography (MM) and magnetic resonance
      imaging (MRI). Fifty-six patients with suspected lesions detected by palpation or
      MM were included in the study. Within the 4 weeks preceding excisional biopsy, MM
      and MRI were performed in all patients. Between 5 and 10 min after the injection
      of 740 MBq 99mTc-MIBI, SMM in the prone position was performed. In the total
      group of 56 patients, 43 lesions were palpable, while 13 were non-palpable but
      were detected by MM. Breast cancer was confirmed by histopathology in 27 of the
      patients (22 palpable and 5 non-palpable carcinomas). The tumour size ranged from
      6 to 80 mm in diameter. For non-palpable lesions, the sensitivity of SMM, MM and
      MRI was 60%, 60% and 100%, respectively, while the specificity was 75%, 25% and
      50%, respectively. For palpable breast lesions, all methods showed high
      sensitivity (SMM 91%, MM 95%, MRI 91%) but SMM demonstrated significantly higher
      specificity (SMM 62%, MM 10%, MRI 15%). In two mammographically negative tumours
      (dense tissue), SMM showed a positive result. In comparison to MRI, one
      additional carcinoma could be diagnosed by SMM. It may be concluded that for
      palpable breast lesions, the diagnostic accuracy of SMM is superior to that of MM
      and MRI. Through the complementary use of SMM it is possible to increase the
      sensitivity for the detection of breast cancer and multicentric disease. In
      patients in whom the status of a palpable breast mass remains unclear, SMM may
      help to reduce the amount of unnecessary biopsies.

PMID- 8753684
TI  - Partition model for estimating radiation doses from yttrium-90 microspheres in
      treating hepatic tumours.
AB  - A uniform distribution of yttrium-90 (90Y) microspheres throughout the entire
      liver has always been assumed for dose calculation in treating hepatic tumours. A
      simple mathematical model was formulated which allows estimation of the
      activities of a therapeutic dose of 90Y microspheres partitioned between the
      lungs, the tumour and the normal liver, and hence the radiation doses to them.
      The doses to the tumour and normal liver were verified by intra-operative direct
      beta-probing. The percentage of activity shunted to the lung and the tumour-to
      normal tissue ratio (T/N) were obtained from gamma scintigraphy using technetium
      99m-labelled macroaggregated albumin (MAA) which simulates the 90Y microspheres
      used in subsequent treatment. The intrahepatic activity was partitioned between
      the tumour and the normal liver based on the T/N and their masses determined from
      computerized tomography slices. The corresponding radiation doses were computed
      using the MIRD formula. The estimated radiation doses were correlated with the
      doses directly measured using a calibrated beta-probe at laparotomy by linear
      regression. The radiation doses to the tumour and the normal liver, estimated
      using the partition model, were close to that measured directly with coefficients
      of correlation for linear regression: 0.862 for the tumours and 0.804 for the
      normal liver compartment (P<0.001). The partition model permits a distinction
      between the radiation doses received by the tumour and the normal liver to be
      made and the doses thus estimated are close to the actual doses received. The
      optimal doses to the tumour and normal liver and hence the required quantity of
      90Y microspheres to be administered can be easily predetermined.

PMID- 8753685
TI  - Application of the linear-quadratic model to myelotoxicity associated with
      radioimmunotherapy.
AB  - The purposes of this study were: (1) to use the linear-quadratic model to
      determine time-dependent biologically effective doses (BEDs) that were delivered
      to the bone marrow by multiple infusions of radiolabeled antibodies, and (2) to
      determine whether granulocyte and platelet counts correlate better with BED than
      administered radioactivity, which does not take stem cell repopulation, i.e.,
      time, into consideration. Twenty patients with B-cell malignancies that had
      progressed despite intensive chemotherapy and who had a significant number of
      malignant cells in their bone marrow were treated with multiple 0.7-3.7 GBq/m2
      (18-100 mCi/m2) intravenous infusions of Lym-1, a murine monoclonal antibody that
      binds to a tumour-associated antigen, labeled with iodine-131. Granulocyte and
      platelet counts were measured in order to assess bone marrow toxicity. BEDs were
      calculated according to the formula: BED=D(1+gD/(alpha/beta))-0.693(Tn
      Tk)/alphaTp, where D represents the absorbed dose of radiation delivered to the
      red marrow by penetrating emissions of 131I throughout the whole body and
      nonpenetrating emissions of 131I in the blood and bone marrow, g is a factor that
      depends on the duration of irradiation relative to the repair half-life of human
      bone marrow, alpha is the coefficient of nonrepairable damage per Gy, beta is the
      coefficient of repairable damage per Gy2, Tn is the time required to reach the
      granulocyte or platelet count nadir after an 131I-Lym-1 infusion, Tk is the time
      at which bone marrow proliferation begins after the start of treatment and Tp is
      the doubling time of the bone marrow after the granulocyte or platelet count
      nadir has been reached. The cumulative 131I-Lym-1 radioactivity administered to
      each patient was calculated. Biologically effective doses from multiple 131I-Lym
      1 infusions were summated in order to arrive at a total BED for each patient.
      There was a weak association between granulocyte and platelet counts and
      radioactivity (the correlation coefficients were -0.23 and -0.60, respectively).
      Likewise, there was a weak association between granulocyte and platelet counts
      and BED (the correlation coefficients were -0.27 and -0.40, respectively). The
      attempt to take bone marrow absorbed doses and overall treatment time into
      consideration with the linear-quadratic model did not produce a stronger
      association than was observed between peripheral blood counts and administered
      radioactivity. The association between granulocyte and platelet counts and BED
      may have been weakened by several factors, including variable bone marrow reserve
      at the start of 131I-Lym-1 therapy and the delivery of heterogeneous absorbed
      doses of radiation to the bone marrow.

PMID- 8753686
TI  - Radiation doses of yttrium-90 citrate and yttrium-90 EDTMP as determined via
      analogous yttrium-86 complexes and positron emission tomography.
AB  - Yttrium-90 is used for palliative therapy for the treatment of skeletal
      metastases, but because it is a pure beta- emitter, data on the pharmacokinetics
      and radiation doses to metastases and unaffected organs are lacking. To obtain
      such data, the present study employed yttrium-86 as a substitute for 90Y, with
      detection by positron emission tomography (PET). The study compared the
      properties of two different 86Y complexes - 86Y-citrate and 86Y-ethylene diamine
      tetramethylene phosphonate (EDTMP) - in ten patients with prostatic cancer who
      had developed multiple bone metastases (the ten patients being divided into two
      groups of five). Early dynamics were measured up to 1 h post injection (p.i.)
      over the liver region, followed by subsequent whole-body PET scans up to 3 days
      p.i. Absolute uptake data were determined for normal bone, bone metastases, liver
      and kidney. Radiation doses were calculated according to the MIRD
      recommendations. Based on the pharmacokinetic measurements of the distribution of
      the 86Y complexes, it was possible to calculate radiation doses for the bone
      metastases and the red bone marrow delivered by complexes containing 90Y. In 1
      cm3 of bone metastasis, doses of 26+/-11 mGy/MBq and 18+/-2 mGy/MBq were
      determined per MBq of injected 90Y-citrate and 90Y-EDTMP, respectively. The doses
      to the bone marrow were 2.5+/-0.4 mGy/MBq for 90Y-citrate and 1.8+/-0.6 mGy/MBq
      for 90Y-EDTMP. 86Y and PET provide quantitative information applicable to the
      clinical use of 90Y. This method may also be useful for the design of other 90Y
      radiopharmaceuticals and for planning radiotherapy dosages.

PMID- 8753687
TI  - The pattern of radionuclide scrotal scan in torsion of testicular appendages.
AB  - The aim of this study was to define the radionuclide scrotal imaging (RSI)
      pattern in cases of torsion of testicular appendages and to correlate it with the
      duration of symptoms. Two hundred and seventeen patients with acute scrotal pain
      were evaluated prospectively during the past 13 years. Two groups of patients
      were defined according to the interval between the onset of symptoms and the
      performance of RSI: group A comprised patients in whom RSI was performed within 5
      h after the onset of symptoms, while group B comprised patients in whom RSI was
      performed between 5 and 24 h after the onset of symptoms. An SPX-4 Elscint or an
      Apex 405 gamma camera with a parallel hole or converging collimator was used.
      Between 5 and 15 mCi of technetium-99m pertechnetate was injected as a bolus
      intravenously. The radionuclide angiogram consisted of six to eight consecutive 5
      s frames. The scrotal static scan was obtained immediately following the
      radionuclide angiogram. The "hot dot" sign, which is a small spot of increased
      tracer perfusion and uptake on RSI, was not present during the first hours after
      the onset of symptoms. Therefore, RSI is inaccurate and is not indicated for the
      diagnosis of torsion of testicular appendages of less than 4-5 h duration. The
      hot dot sign was, however, demonstrated on the RSI in 45% of the patients with
      scrotal pain lasting between 5 and 24 h. The overall sensitivity and accuracy of
      RSI in diagnosing torsion of testicular appendages in this group of patients were
      68% and 79%, respectively. In all the patients with a positive hot dot sign,
      torsion of testicular appendages was found at exploration (specificity 100%).
      Therefore, the hot dot sign was found to be pathognomonic of torsion of
      testicular appendages.

PMID- 8753688
TI  - Magnetic resonance imaging versus bone scintigraphy in suspected scaphoid
      fracture.
AB  - Magnetic resonance imaging (MRI) has become increasingly useful in the evaluation
      of musculoskeletal problems, including those of the wrist. In patients with a
      wrist injury, MRI is used mainly to assess vascularity of scaphoid non-union.
      However, the use of MRI in patients in the acute phase following carpal injury is
      not common. Three-phase bone scintigraphy is routinely performed from at least 72
      h after injury in patients with suspected scaphoid fracture and negative initial
      radiographs. We evaluated MRI in this patient group. The bone scan was used as
      the reference method. Nineteen patients were included. Bone scintigraphy was
      performed in all 19 patients, but MRI could be obtained in only 16 (in three
      patients, MRI was stopped owing to claustrophobia). In five patients, MRI
      confirmed a scintigraphically suspected scaphoid fracture. In one patient, a
      perilunar luxation, without a fracture, was seen on MRI, while bone scintigraphy
      showed a hot spot in the region of the lunate bone, suspected for fracture. This
      was confirmed by surgery. In two patients, a hot spot in the scaphoid region was
      suspected for scaphoid fracture, and immobilization and employed for a period of
      12 weeks. MRI was negative in both cases; in one of them a scaphoid fracture was
      retrospectively proven on the initial X-ray series. In another two patients, a
      hot spot in the region of MCP I was found with a negative MRI. In both, the
      therapy was adjusted. In the remaining six patients, both modalities were
      negative. We conclude that in the diagnostic management of patients with
      suspected scaphoid fracture and negative initial radiographs, the use of MRI may
      be promising, but is not superior to three-phase bone scintigraphy.

PMID- 8753689
TI  - 99mTc-MIBI scintigraphy in metastatic renal cell carcinoma: clinical validation
      of the relationship between 99mTc-MIBI uptake and P-glycoprotein expression in
      tumour tissue.
AB  - Technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI) and thallium-201
      imaging was performed in a patient with metastatic renal cell carcinoma (RCC),
      which is a well-known tumour type demonstrating P1-glycoprotein (PGP)
      overexpression. Two scintigraphic patterns - Tl(+)/MIBI(-) in primary tumour and
      Tl(+)/MIBI(+) in metastatic tumour - were observed, suggesting high- and low
      level PGP expression, respectively. Immunochemical study for PGP revealed strong
      staining of the primary tumour cells. This case clinically validates the
      previously suggested relationship between 99mTc-MIBI uptake and PGP expression.

PMID- 8753690
TI  - Primary breast cancer imaging with technetium-99m sestamibi and its relation with
      P-glycoprotein overexpression.
AB  - The aim of this preliminary study was to evaluate retrospectively sestamibi
      scintigraphy in relation to the presence of the 170-kDa P-glycoprotein (Pgp),
      which represents an expression of multidrug resistance in patients with primary
      breast cancer. Fifteen women (age range 37-76 years) were referred for technetium
      99m sestamibi scintigraphy because of suspicious breast lesions detected by
      mammography and ultrasonography, and subsequently assessed by fine-needle
      aspiration. Scintigraphy was performed 30 min following the injection of 500 MBq
      99mTc-sestamibi. Three planar anterior and oblique images were obtained with the
      patient in the supine position. Excised tumours were assessed for cytosolic CA
      15.3, oestrogen (OR) and progesterone (PR) receptors and c-erb B2 neu oncogene.
      Pathology revealed that only 13 of the 15 patients had malignant tumours. The two
      benign tumours were sestamibi-negative and Pgp-positive. Sestamibi scintigraphy
      was positive in 10 of the 13 malignant lesions (including nine of ten
      infiltrating ductal carcinomas). Two of the three lesions with false-negative
      scintigraphy were Pgp-negative; in one of these cases histology revealed an
      invasive lobular carcinoma and in the other, mucinous adenocarcinoma. The third
      false-negative lesion was a Pgp-positive infiltrating ductal carcinoma which was
      c-erb B2 neu-negative but CA 15.3-, OR- and PR-positive. This preliminary study
      confirms that the resistance to chemotherapy which may occur in patients with
      primary breast cancer can be a cause of negative sestamibi scintigraphy.

PMID- 8753691
TI  - Indium-111 octreotide scintigraphy in patients with bone tumours of the
      extremities.
AB  - Radiolabelled somatostatin analogues are of potential value in the imaging of
      somatostatin receptor-positive tumours. Recently, somatostatin receptors have
      been demonstrated in the osteoblast precursor cells. In this preliminary study,
      we evaluated the uptake characteristics of indium-111 octreotide in two benign
      and two malignant bone tumours. Tracer accumulation was observed in all four
      cases, and overall lesion to background ratio (mean+/-SD) was 2. 74+/-0.84 and
      2.98+/-1.49 at 4 h and 24 h, respectively. There was no clear relationship
      between 111In-octreotide accumulation and the benign or malignant nature of the
      tumour. In one patient, tracer uptake was inhibited by unlabelled octreotide
      administration. These results suggest that 111In-octreotide can be taken up by
      benign and malignant bone tumours. The inhibition of tumour uptake by treatment
      with cold octreotide supports the concept that specific uptake mechanisms are
      responsible for 111In-octreotide deposition by bone tumours.

PMID- 8753692
TI  - The effect of steroid on thallium-201 uptake by malignant gliomas.
AB  - In order to assess the effect of steroid on thallium-201 uptake by glioma, 201Tl
      single-photon emission tomography was performed before and after steroid
      administration in four patients with recurrent malignant glioma. After steroid
      administration the 201Tl index, expressed as the ratio of 201Tl uptake in the
      tumour to that in the contralateral cerebral hemisphere, was 0.77+/-0.11 of the
      value before steroid (mean+/-SD: P<0.05 by paired t test). The 201Tl index has
      been used as a possible indicator for the differentiation of malignant gliomas
      from relatively benign tumours or radiation necrosis. The present results
      indicate that the effect of steroid has to be taken into account when semi
      quantitative analysis, e.g. by means of the 201Tl index, is used in patients with
      brain tumours.

PMID- 8753694
TI  - Problems associated with the clinical use of radiopharmaceuticals: a proposed
      classification system and troubleshooting guide.
AB  - Problems associated with the clinical use of radiopharmaceuticals can usually be
      classified into one of four categories: unusual imaging results, adverse
      reactions, unique difficulties encountered in special patient populations, and
      quality assurance failures. Each of these problem areas is briefly described and
      a guide for troubleshooting such problems is presented.

PMID- 8753693
TI  - Measurement of cardiac output with first-pass determination during rubidium-82
      PET myocardial perfusion imaging.
AB  - In addition to providing useful clinical information, cardiac output determined
      during rubidium-82 positron emission tomographic (PET) myocardial perfusion
      studies can be used in the measurement of absolute regional myocardial blood flow
      using Sapirstein's method. This investigation was conducted to compare cardiac
      output values obtained by post-processing data acquired in a list mode PET
      myocardial perfusion study with those obtained using a technetium-99m-labeled red
      blood cell method on the same patients. Results from 14 patients showed that
      cardiac output can be accurately measured simultaneously in a 82Rb PET myocardial
      study, allowing determination of multiple perfusion and functional parameters of
      the heart, thus improving the cost-effectiveness of the 82Rb PET study.

PMID- 8753695
TI  - Didactic review of 175 radionuclide-guided excisions of osteoid osteomas.
AB  - The complete removal of a lesion which resembles, or is covered by adjacent
      tissue may be difficult. Therefore, the capacity of certain lesions to
      specifically concentrate a radiopharmaceutical has been used to orient progress
      during surgery. Usually, the measurements of radioactivity in the operative field
      are carried out by means of small, handy radiation-detecting probes which can be
      sterilized. "Intra-operative nuclear medicine" or "radionuclide-guided surgery"
      has steadily gained in importance. However, this technique is not being taught.
      Our study, based on radionuclide-guided surgery of 175 orthopaedic patients
      suspected of having osteoid osteoma, is well suited to teach the particularities
      of intra-operative radiation detection, as well as the collaboration between the
      nuclear physician and the surgeon in the operating theatre.

PMID- 8753697
TI  - rTP: a candidate telomere protein that is associated with DNA replication.
AB  - In this paper we describe the isolation and characterization of rTP, the
      replication Telomere Protein, formerly known as the telomere protein homolog. The
      rTP was initially identified because of its homology to the gene for the
      Oxytricha telomere-binding protein alpha-subunit. The protein encoded by the rTP
      gene has extensive amino acid sequence identity to the DNA-binding domain of the
      telomere-binding proteins from both Euplotes crassus and Oxytricha nova. We have
      now identified the protein encoded by the rTP gene and have shown that it differs
      from the telomere-binding protein in its abundance, solubility and intracellular
      location. To learn more about the function of rTP, we determined when during the
      Euplotes life cycle the gene is transcribed. The transcript was detectable only
      in nonstarved vegetative cells and during the final stages of macronuclear
      development. Since the peak transcript level coincided with the rounds of
      replication that take place toward the end of macronuclear development, it
      appeared that rTP might be involved in DNA replication. Immunolocalization
      experiments provided support for this hypothesis as antibodies to rTP
      specifically stain the replication bands. Replication bands are the sites of DNA
      replication in Euplotes macronuclei. Our results suggest that rTP may be a new
      telomere replication factor.

PMID- 8753696
TI  - Analysis of extrachromosomal structures containing human centromeric alphoid
      satellite DNA sequences in mouse cells.
AB  - Yeast artificial chromosomes (YACs) spanning the centromeric region of the human
      Y chromosome were introduced into mouse LA-9 cells by spheroplast fusion in order
      to determine whether they would form mammalian artificial chromosomes. In about
      50% of the cell lines generated, the YAC DNA was associated with circular
      extrachromosomal structures. These episomes were only present in a proportion of
      the cells, usually at high copy number, and were lost rapidly in the absence of
      selection. These observations suggest that, despite the presence of centromeric
      sequences, the structures were not segregating efficiently and thus were not
      forming artificial chromosomes. However, extrachromosomal structures containing
      alphoid DNA appeared cytogenetically smaller than those lacking it, as long as
      yeast DNA was also absent. This suggests that alphoid DNA can generate the
      condensed chromatin structure at the centromere.

PMID- 8753698
TI  - Relationship between the levels of wheat-rye metaphase I chromosomal pairing and
      recombination revealed by GISH.
AB  - The metaphase I and anaphase I stages of meiosis of wheat x rye hybrids carrying
      the ph1b mutation were analyzed by genomic in situ hybridization. This technique
      allows distinction between three different types of wheat-rye associations in
      metaphase I configurations as well as detection of wheat-rye recombinant
      chromosomes in anaphase I cells. The frequency of associations between wheat and
      rye chromosomes greatly exceeded the level of wheat-rye recombination found in
      the three hybrids examined. Extremely distal associations, which account for
      about 50% of the total wheat-rye metaphase I chromosomal pairing, can explain
      such a discrepancy between metaphase I and anaphase I data. It is further
      discussed whether these associations reflect very distally located chiasmata or
      nonchiasmatic pairing. The sizes of the segments exchanged in wheat-rye
      recombinant chromosomes provide cytological evidence that wheat-rye recombination
      is restricted to the distal chromosomal regions.

PMID- 8753699
TI  - Molecular cytogenetic characterisation of the terminal heterochromatic segment of
      the B-chromosome of rye (Secale cereale).
AB  - The terminal heterochromatic segments of the long arms of 20 rye B-chromosomes
      were isolated by means of laser microdissection technology. Also the remaining
      portions of the long arms, along with the short arms of the same chromosomes were
      isolated. Each sample was used for degenerate oligonucleotide primer-polymerase
      chain reaction (DOP-PCR) amplification reactions. The resulting products were
      used as probes for chromosome in situ hybridisation experiments, and in Southern
      hybridisation to digests of 0B and +B DNA. Competition hybridisation of these
      probes with 0B DNA allowed the detection of B-specific sequences. The terminal
      heterochromatin of the rye B-chromosome contains both B-specific sequences and
      sequences also present on the A-chromosomes of rye. The B-specific D1100 family
      is the major repeat species located in the terminal heterochromatin. Primers
      designed to the cloned sequence (E1100) were used to search for related low copy
      sequences in 0B DNA. The sequences of the PCR products revealed no similarities
      to that of the clone E1100 except for the primer sequences. The possible origin
      of this sequence is discussed in the context of models for the evolution of the
      rye B-chromosome.

PMID- 8753700
TI  - The heat shock genes in the Drosophila montium subgroup: chromosomal localization
      and evolutionary implications.
AB  - The hsp70, hsp83, hsromega, and the small heat shock protein genes were mapped on
      the polytene chromosomes of six species, representative of the geographical
      distribution of the Drosophila montium subgroup of the melanogaster species
      group. In addition, based on hybridization conditions, the putative locus of the
      hsp68 gene is given. In contrast to the situation in the melanogaster subgroup
      species, the hsp70 locus is single in the montium species. The hsp83, hsromega
      and the small hsp loci are also single in the montium genomes studied here, a
      common feature of all Drosophila species. Among the hsp genes studied, the small
      hsp genes and the hsromega-homologous sequences exhibit a higher degree of
      divergence between the melanogaster and the montium subgroups. Our results
      support the idea that the montium subgroup species has a genome organization
      closer to that of the common ancestor compared with the melanogaster subgroup
      species.

PMID- 8753701
TI  - Structural changes in oocyte nucleoli of Xenopus laevis during oogenesis and
      meiotic maturation.
AB  - Immunoelectron microscopy with anti-nucleolin defined substructures within the
      multiple nucleoli of biosynthetically active stage II-III oocytes and within the
      nucleoli of relatively quiescent stage VI oocytes of Xenopus laevis. Dense
      fibrillar components (DFCs) of nucleoli from stage II-III oocytes consisted of
      nucleolonemas that radiated from a continuous DFC sheath surrounding fibrillar
      centers (FCs). Discernible granular regions (GRs) were absent in these same
      nucleoli. Conversely, stage VI oocyte nucleoli displayed compacted DFCs and
      prominent GRs. Immunofluorescence microscopy then tracked fibrillarin, nucleolin,
      and condensed DNA through oogenesis and into progesterone-induced meiotic
      maturation and nuclear breakdown. In stage II-III oocyte nucleoli, fibrillarin
      was enriched near the FC-DFC boundaries, while nucleolin was distributed
      throughout these same DFCs. Both proteins were enriched within the compacted DFCs
      of stage VI oocyte nucleoli. Staining with (DAPI) 4',6-diamidino-2-phenylindole
      showed condensed DNA within nucleolar FCs of both stage II-III and stage VI
      oocyte. Upon nuclear breakdown, we found fibrillarin and nucleolin in small
      particles and in the surrounding cytoplasm. Although we saw no trace of
      fibrillarin or nucleolin in nuclear remnants prepared just minutes later, DAPI
      stained particles remained within these preparations, thus suggesting that FCs
      were at least slow to disassemble.

PMID- 8753703
TI  - The Renaissance revisited.

PMID- 8753704
TI  - Mentor, peer, and protege.

PMID- 8753702
TI  - Scaffold attachment regions in centromere-associated DNA.
AB  - Due to indications that kinetochore proteins are an integral part of the protein
      scaffold component of the chromosome (Earnshaw et al. 1984), we chose to map the
      distribution of scaffold attachment regions (SARs) at centromeres. Using the SAR
      mapping assay of Mirkovitch et al., Southern blots were prepared and probed with
      32P-labeled fragments from the human 1.9 kb centromeric alpha-satellite repeat
      unit of chromosome 1 or the 1.7 kb centromeric alpha-satellite repeat unit of
      chromosome 16. Our results demonstrated the presence of one SAR site per 1.9 kb
      repeat unit in chromosome 1, and every 1.7 kb repeat unit in chromosome 16,
      separated by regions of small DNA loops over the length of the alpha-satellite
      regions. We also identified several in vitro vertebrate topoisomerase II and cenP
      B consensus sequences throughout the chromosome 1 alpha-satellite region using
      computer and base ratio analysis, to address the question as to why some alpha
      satellite regions are SAR related and others are not. To provide in situ
      indications of SAR localization in the human genome, SAR DNA and non-SAR DNA were
      prepared following lithium 3,5-di-iodosalicylate extraction. Sequences protected
      from DNAse I digestion by SAR proteins, as compared with unprotected DNA that was
      digested by the enzyme, was labeled with biotin-UTP, hybridized to chromosomal
      DNA in situ, and then detected with fluorescein-avidin-DCS. Both SAR and non-SAR
      DNA selectively labeled virtually all centromeric regions of the human metaphase
      karyotype. Chromosomal arms were less strongly bound by SAR DNA, with a pattern
      that followed the chromosomal axis. In the more condensed chromosomes an R
      banding pattern was evident. In general, labeling patterns produced by both SAR
      and non-SAR fractions were similar, as expected from the indications that SAR
      DNAs are heterogenous in sequence and do not form a specific class of sequences.
      We conclude that centromeric regions of several, possibly all, human metaphase
      chromosomes are also regions where the chromosomal axis contains loops, smaller
      in size than in the arms and where attachment sites are concentrated. This
      clustering of SARs may be responsible in part for the tight chromatin packing
      associated with the primary constriction of the centromeric region.

PMID- 8753705
TI  - Juvenile idiopathic scoliosis. Curve patterns and prognosis in one hundred and
      nine patients.
AB  - We reviewed the medical records and radiographs of 109 consecutive patients who
      had juvenile idiopathic scoliosis. The sixty-seven girls and forty-two boys were
      a mean of six years and ten months old (range, three years and four months to
      nine years and eleven months old) when the curve was recognized. One hundred and
      four patients had a progressive curve: twenty-eight had a single mid-thoracic
      curve with the apex usually at the eighth thoracic vertebra (Group 1A), twenty
      nine had a major mid-thoracic curve with the apex usually at the eighth thoracic
      vertebra and a secondary minor lumbar curve (Group 1B), twenty-seven had a single
      thoracic curve with the apex usually at the ninth or tenth thoracic level (Group
      2), eight had a single thoracolumbar curve with the apex at the twelfth thoracic
      level (Group 3), and twelve had a major lumbar curve with the apex at the second
      or third lumbar level and a secondary minor thoracic curve (Group 4). Five
      patients (5 per cent) had a resolving curve. Eighty-nine of the patients who had
      a progressive curve were followed to skeletal maturity. Eighty-eight patients
      were managed with a brace. The curve progressed at a rate of 1 to 3 degrees per
      year before the age of ten years and 4.5 to 11 degrees per year after the age of
      ten years. In sixty-seven of the eighty-four patients in Groups 1 and 2, a spinal
      arthrodesis was performed before the age of fifteen years (mean age, eleven years
      and ten months; range, nine years and three months to fourteen years and eight
      months), at which time the mean curve was 47 degrees (range, 24 to 90 degrees).
      Eight patients were not seen by us until they were fifteen years old or more, at
      which time the thoracic curve was 74 to 120 degrees; a spinal arthrodesis was
      done in seven. The curves in Groups 3 and 4 had a more benign prognosis, and only
      three patients in these two groups had an arthrodesis. The pattern of the final
      curve was not always apparent at an early stage, and there was extension of the
      primary curve or development of secondary structural curves with progression. The
      chief prognostic feature at an early stage was the level of the most rotated
      vertebra at the apex of the primary curve, and the final pattern of deformity was
      defined by the level of the caudad neutral vertebra in the primary thoracic
      curve.

PMID- 8753706
TI  - Slipped capital femoral epiphysis. Prediction of contralateral involvement.
AB  - We performed a retrospective review of the medical records and radiographs of
      fifty children who had had unilateral slipped capital femoral epiphysis. Our
      purpose was to determine if there were any epidemiological parameters that were
      associated with the later development of a contralateral slip. The mean duration
      of follow-up was thirty-four months (range, twenty-four to sixty-eight months).
      Physiological maturity, determined with a modified form of the Oxford method for
      assessment of bone age, strongly correlated with the risk of development of a
      contralateral slip in patients who were initially seen with a unilateral slip (r
      = 0.59, p < 0.0005). The scores were determined by four raters; the variation in
      the predictive value of the scores among the raters was not significant (p =
      0.5). The relationship between the score as determined with the modified Oxford
      method and the risk of contralateral involvement had a linear distribution. The
      four raters performed a total of 442 observations to determine the modified
      Oxford scores for the fifty hips. The prevalence of a subsequent slip for the
      hips that had been assigned a score of 16 points was 85 +/- 15 per cent (95 per
      cent confidence limit) (seventeen of twenty observations). The risk of
      contralateral involvement when the score was 21 points was 11 +/- 9 per cent (six
      of fifty-four observations). A slip did not develop in any hip with a score of 22
      points or more (sixty-nine observations). For boys, the age at the time of the
      initial slip was predictive of a contralateral slip. A contralateral slip
      developed in all four boys who had been eleven years and seven months old or less
      at the time of the initial presentation; however, a contralateral slip developed
      in only nine of the twenty-two boys who had been eleven years and eight months to
      fourteen years and eleven months old. A contralateral slip did not develop in the
      three boys who had been fifteen years old or more. There was no association
      between age and the risk of a contralateral slip in girls.

PMID- 8753707
TI  - Burst fractures of the second through fifth lumbar vertebrae. Clinical and
      radiographic results.
AB  - Fifty-five patients who had sustained a burst fracture of the lumbar spine were
      followed for a mean of seventy-nine months (range, twenty-four to 192 months)
      after the injury. Thirty patients had been managed non-operatively with a short
      period of bed rest followed by protected mobilization. The remaining twenty-five
      patients had been managed operatively: eight, with posterior arthrodesis with
      long-segment hook-and-rod fixation; eight, with posterior arthrodesis with short
      segment transpedicular fixation; six, with posterior arthrodesis and
      instrumentation followed by anterior decompression and arthrodesis; and three,
      with anterior decompression and arthrodesis. Thirty-six patients had been
      neurologically intact at the time of presentation and had remained so throughout
      the follow-up period. No neurological deterioration or symptoms of late spinal
      stenosis were seen. Isolated partial single-nerve-root deficits resolved
      regardless of the method of treatment. Patients who had had a complete single or
      a multiple-nerve-root paralysis seemed to have benefited from anterior
      decompression. Although the anatomical results as seen on the most recent
      radiographs were superior for the group that had been managed operatively with
      long posterior fixation or anterior and posterior arthrodesis, the most recent
      pain scores and the functional outcomes were similar for all treatment groups. At
      the latest follow-up evaluation, some loss of spinal alignment was noted in the
      patients who had been managed with short transpedicular fixation; the alignment
      at the most recent follow-up examination was comparable with that in the patients
      who had been managed non-operatively. For the patients who had had non-operative
      treatment, we were unable to predict the deformity at the time of follow-up on
      the basis of the initial diagnostic radiographs. The clinical outcome was not
      related to the deformity at the latest follow-up evaluation. On the basis of the
      results of our study, we recommend non-operative treatment for patients who do
      not have neurological dysfunction or who have an isolated partial nerve-root
      deficit at the time of presentation. For patients who have a multiple-nerve-root
      paralysis, anterior decompression is indicated.

PMID- 8753709
TI  - Osteoma of the long bones and the spine. A study of eleven patients and a review
      of the literature.
AB  - The clinical features, radiographic and histopathological findings, treatment,
      and results are described for eleven patients who were managed for an
      extracranial osteoma at our medical center between 1980 and 1993. Ten of the
      patients were initially seen because of dull, aching bone pain that had been
      present for two weeks to thirty years. Radiographs demonstrated single or
      multiple homogeneous, well defined, radiodense foci with smooth round or
      lobulated margins. The histopathological features consistently included uniformly
      dense, compact, cortical-like, mature lamellar bone. The preoperative diagnosis
      was unclear for all patients, and osteoma was rarely considered in the
      differential diagnosis. For four patients, a tentative diagnosis of osteosarcoma
      was made, and a wide excision was carried out in two of these patients. Marginal
      excision with less than three millimeters of normal tissue around the lesion was
      performed in most patients. None of the osteomas recurred, and ten patients had
      relief of the pain. Awareness of the clinical, radiographic, and
      histopathological features of osteoma, as described, is valuable for making a
      differential diagnosis and for distinguishing osteomas from other lesions.

PMID- 8753708
TI  - Comparison of intravenous and oral antibiotic therapy in the treatment of
      fractures caused by low-velocity gunshots. A prospective, randomized study of
      infection rates.
AB  - One hundred and ninety consecutive patients (222 fractures) who had an extra
      articular fracture of a long bone as a result of a low-velocity gunshot were
      randomized into two groups on the basis of the method of administration of
      antibiotics. Group 1 consisted of 101 patients (120 fractures) who were managed
      with intravenous administration of cephapirin sodium and gentamicin for three
      days. Group 2 comprised eighty-nine patients (102 fractures) who were managed
      with oral administration of ciprofloxacin for three days. The two groups were
      comparable in terms of the age of the patient, the locations of the fractures,
      and the time from the injury to the commencement of antibiotic therapy. Injuries
      that needed operative debridement or fixation were excluded. All patients were
      followed until the fracture had healed. Two infections developed in two of the
      ninety-nine patients (118 fractures) who completed the study in Group 1, and two
      infections developed in two of the eighty-seven patients (100 fractures) who
      completed the study in Group 2. With the numbers available, there was no
      significant difference in the rates of infection (2 per cent for both) between
      the two groups. All four fractures that were complicated by infection were
      located in the distal half of the tibia. We concluded that oral and intravenous
      administration of antibiotics were equally effective for prophylaxis against
      infection after an extra-articular fracture from a low-velocity gunshot.

PMID- 8753710
TI  - Increased levels of tumor necrosis factor-alpha and interleukin-6 protein and
      messenger RNA in human peripheral blood monocytes due to titanium particles.
AB  - Cytokines produced by macrophages in the periprosthetic membranes surrounding
      joint replacements have been implicated as causal agents in osteolysis and
      prosthetic loosening. The present study characterizes the response of human
      peripheral blood monocytes to titanium particles. Monocytes were obtained from
      volunteers and blood that had been donated to the American Red Cross and were
      cultured in the presence of titanium particles (one to three micrometers in
      diameter). There were consistent dose-dependent increases in the production of
      TNF-alpha (tumor necrosis factor-alpha) and IL-6 (interleukin-6) protein, with
      the greatest stimulation generally observed with a concentration of 6 x 10(5) to
      6 x 10(6) particles of titanium per milliliter. The level of TNF-alpha was the
      greatest (fifty to 1000 times greater than the control level) after eight hours
      of exposure to titanium particles; the level of IL-6 was two to five times
      greater than the control level after sixteen hours of exposure. These increases
      were similar to those observed after stimulation with lipopolysaccharide and
      depended on de novo synthesis rather than on release from intracellular stores.
      The production of TNF-alpha was inhibited in a dose-dependent manner by the
      translational inhibitor cycloheximide and the transcriptional inhibitor
      actinomycin D, indicating the requirement for both mRNA (messenger RNA) and
      protein synthesis for the induction of cytokine synthesis by titanium particles.
      Although the increase in the levels of cytokine mRNA in response to titanium was
      rapid (thirty to ninety minutes), the increase in the level of TNF-alpha mRNA
      preceded that of IL-6 mRNA. The level of TNF-alpha mRNA was the greatest at
      ninety minutes and the level of IL-6 mRNA was the greatest at three hours. After
      stimulation with titanium particles, the level of TNF-alpha mRNA was increased as
      much as fivefold and the level of IL-6 mRNA, as much as twelvefold.

PMID- 8753711
TI  - Wear of polyethylene cups in total hip arthroplasty. A study of specimens
      retrieved post mortem.
AB  - The wear of polyethylene components of total hip replacements has previously been
      studied radiographically and by analysis of retrieved components. The extent of
      wear, however, has largely been determined from components retrieved at
      reoperation and has therefore been based on a subset of patients in whom the
      prosthesis is more likely to show excessive wear. The study of cups retrieved
      post mortem provides a better indication of the extent of wear of well
      functioning components. Twenty-six polyethylene liners were retrieved at autopsy
      from nineteen patients, after a mean of ninety-one months (range, thirty-three to
      206 months) in situ. Each component had articulated with a thirty-two-millimeter
      diameter femoral head. The components were evaluated visually for evidence of
      polyethylene wear such as pitting, scratching, and burnishing. Additionally; a
      shadowgraph technique was used to examine molds of the inner surface of the liner
      to determine the direction and extent of wear. The mean extent of linear wear of
      the retrieved liners was 0.45 millimeter (range, 0.17 to 1.07 millimeters), and
      the mean rate of wear was 0.07 millimeter (range, 0.02 to 0.18 millimeter) per
      year. The mean volumetric wear was 245.3 cubic millimeters (range, 13.0 to 779.1
      cubic millimeters), and the mean rate of volumetric wear was 39.8 cubic
      millimeters (range, 1.0 to 131.3 cubic millimeters) per year. The mean rate of
      wear for the twenty-six liners was 45 to 69 per cent less than the rates reported
      in the literature for polyethylene liners retrieved at reoperation. Examination
      of the articulating surface did not reveal gross evidence of surface failure such
      as delamination or fatigue cracks. In general, the surfaces were merely burnished
      and scratched. The rates of wear of press-fit, metal-backed liners were
      significantly higher than those of all-polyethylene cemented components (p <
      0.05). Additionally, statistical analysis revealed no correlation between wear
      and the patient's age, weight, or gender; the duration of implantation; or the
      thickness of the polyethylene. These results indicate that wear of the
      polyethylene of well functioning hip replacements is not as excessive as reported
      previously.

PMID- 8753712
TI  - Effect of intraoperative blood loss on the serum level of cefazolin in patients
      managed with total hip arthroplasty. A prospective, controlled study.
AB  - The effect of intraoperative blood loss on serum levels of cefazolin in patients
      being managed with total hip arthroplasty was studied. Eighteen patients,
      thirteen men and five women, with a mean age of sixty-five years (range, forty to
      eighty-five years) were enrolled in the study. Fifteen had a primary total hip
      arthroplasty and three, a revision. Each patient served as his or her own
      control. Baseline clearance of cefazolin was determined at a minimum of forty
      eight hours before the operation. Each patient received one gram of cefazolin
      intravenously. Serial serum concentrations were determined from specimens drawn
      at zero, five, ten, twenty, thirty, sixty, 120, 240, and 300 minutes after
      administration. Fifteen minutes before the skin incision was made, each patient
      again received one gram of cefazolin intravenously. Serum samples were collected
      at the same time-intervals, and the serum levels of cefazolin were determined
      with use of capillary electrophoresis. Data regarding intraoperative blood loss
      as well as replacement of fluid and blood were recorded. The administration of
      the antibiotic, retrieval of the serum samples, and estimation of the blood loss
      were performed by the same person in the same manner for all patients. The
      preoperative and intraoperative creatinine clearances (mean and standard
      deviation), estimated with use of the formula of Cockcroft and Gault, were 62.06
      +/- 21.28 and 74.02 +/- 24.75 milliliters per minute, respectively. The amount of
      intraoperative blood loss averaged 1137 +/- 436 milliliters (range, 675 to 2437
      milliliters). The preoperative and intraoperative cefazolin clearances averaged
      0.49 +/- 0.21 and 0.52 +/- 0.30 milliliter per minute per kilogram, respectively.
      During joint replacement, the commonly accepted interval between doses of
      cefazolin is four hours. In the present study, the serum level of cefazolin at
      four hours was forty-five micrograms per milliliter. This corresponds to an
      osseous concentration that well exceeds the minimum inhibitory concentration for
      Staphylococcus aureus, which is 0.5 microgram per milliliter. This study suggests
      that, with blood losses of less [corrected] than 2000 milliliters, it is not
      necessary to administer cefazolin at intraoperative intervals of less than four
      hours in order to maintain a concentration of antibiotics that is higher than the
      minimum inhibitory concentration for the most common infecting organisms.

PMID- 8753713
TI  - Periprosthetic fracture of the acetabulum after total hip arthroplasty.
AB  - Eleven patients who had sustained a periprosthetic fracture of the acetabulum at
      a mean of 6.2 years (range, one month to thirteen years) after a total hip
      arthroplasty were managed at our institution between 1985 and 1991. Five patients
      had a fracture of the medial wall; three, a fracture of the posterior column;
      two, a transverse fracture; and one, a fracture of the anterior column. Six
      fractures were displaced by two millimeters or more. Eight fractures were caused
      by blunt trauma or a fall, and three occurred spontaneously. A fracture was
      classified as type 1 if the acetabular component was clinically and
      radiographically stable (eight patients) and as type 2 if the component was
      unstable (three patients). One patient, who had a displaced type-2 fracture of
      the posterior column, died of an associated intrapelvic vascular injury. The
      other two patients who had a type-2 fracture were managed with revision of the
      acetabular component without supplemental plate fixation, immediately after the
      diagnosis of the fracture. The eight patients who had a type-1 fracture initially
      were managed with limitation of weight-bearing or modification of activity; in
      six of these patients, the fracture united without additional treatment. The ten
      surviving patients were followed for a mean of sixty-two months after the
      fracture. Eight of these patients-including four in whom a type-1 fracture had
      united after non-operative treatment-had a revision of the acetabular component
      because of pain, loosening, or non-union by the time of the most recent follow
      up. Two patients (one of whom had a type-1 fracture and the other, a type-2
      fracture) had multiple revisions of the acetabular component; both had
      supplemental internal fixation with a plate. All ten patients ultimately had a
      stable, functioning prosthesis. We conclude that periprosthetic acetabular
      fractures are associated with a poor prognosis with regard to the survival of the
      acetabular component but that it is possible to achieve union and to salvage a
      functional prosthesis in patients who have sustained such a fracture.

PMID- 8753714
TI  - A tapered titanium femoral stem inserted without cement in a total hip
      arthroplasty. Radiographic evaluation and stability.
AB  - The results of 416 total hip arthroplasties performed in 372 patients with
      insertion of a Mallory-Head titanium femoral component without cement were
      reviewed retrospectively, to determine the stability and the radiographic
      parameters of stability for this type of stem. The average duration of clinical
      and radiographic follow-up was 3.7 years (range, 2.0 to 6.5 years). No revisions
      were performed to treat instability of the stem, pain, or osteolysis by the time
      of the latest follow-up examination. Although the clinical results were
      excellent, the radiographic signs of fixation that have been well described for
      chromium-cobalt stems were frequently absent. So-called endosteal spot welds,
      commonly seen in association with long, extensively coated stems, were seen
      infrequently. Resorptive bone-remodeling rarely extended beyond zones 1 and 7 of
      Gruen et al. Both endosteal and periosteal distal cortical hypertrophy was
      common, but the cause was unknown. Osteolysis of the distal aspect of the femur,
      shedding of the porous coating, and breakage of the stem were not seen. Forty
      four stems (11 per cent) had initial subsidence; however, it nearly always
      stabilized within six months postoperatively and did not affect the eventual
      stability at the time of the short-term follow-up. The short-term clinical
      outcome confirmed the stability of these stems that had been determined from the
      radiographic findings and the lack of revisions. At the latest follow-up
      examination, 323 (87 per cent) of the patients (362 [87 per cent] of the hips)
      had no or slight pain in the lower limb over-all and only twenty-two (6 per cent)
      of the patients (twenty-seven [6 per cent] of the hips) had pain in the thigh.
      This tapered titanium femoral component appears to provide excellent short-term
      stability, without resorptive bone-remodeling, osteolysis, or a high prevalence
      of pain in the thigh. Radiographic evaluation of stability of this stem is
      clearly different from that of chromium-cobalt stems-particularly extensively
      coated anatomic medullary locking stems-in that so-called spot welds and severe
      resorptive bone changes were uncommon and distal cortical hypertrophy was common.

PMID- 8753715
TI  - Remodeling of bone around hydroxyapatite-coated femoral stems.
AB  - Two hundred and twenty-four total hip arthroplasties were performed in 201
      patients with use of a femoral component with hydroxyapatite coating of the
      proximal portion of the stem. The mean duration of follow-up was seventy-one
      months (range, fifty-eight to eighty-seven months). Of the 224 arthroplasties,
      208 (93 per cent; 190 patients) yielded a good or excellent clinical result. Four
      patients (2 per cent) reported mild-to-moderate activity-related pain in the
      thigh, and two (1 per cent) had aseptic loosening. The radiographic findings of
      progressive new-bone formation (cancellous condensation and cortical hypertrophy)
      throughout the zones adjacent to the middle and distal portions of the stem were
      evidence of early, extensive proximal fixation of the implant, with distal stress
      transfer through the implant, which is stiffer than the surrounding bone.
      Remodeling of the femur began early, was predictable, and progressed throughout
      the follow-up period. Cortical hypertrophy about the middle and distal portions
      of the stem occurred predominantly in the mediolateral plane (in 105 hips [47 per
      cent], compared with thirteen hips [6 per cent] in the anteroposterior plane),
      and it was more common in patients who had had poorer bone quality
      preoperatively. Intramedullary osteolysis was present in one femur (0.4 per cent)
      at five years; the osteolytic area was less than five millimeters in its greatest
      dimension and had not progressed at the time of the six-year follow-up
      evaluation. This low rate of osteolysis suggests that a circumferential coating
      of hydroxyapatite may effectively minimize migration of wear debris along the
      femoral stem. The progressive remodeling of the femur about the middle and distal
      portions of the stem, as evidenced by cancellous condensation and cortical
      hypertrophy, has not, to our knowledge, been described previously to this
      magnitude in association with proximally coated (porous or hydroxyapatite-coated)
      femoral implants.

PMID- 8753716
TI  - Characterization and comparison of wear debris from failed total hip implants of
      different types.
AB  - Particles of wear debris have been associated with loosening of implants and with
      osteolysis, but few studies have examined the relationship between
      characteristics of the implant and clinical variables and the concentration of
      particles isolated from periarticular tissues. We isolated and quantified
      particles of wear debris from orthopaedic implants in 123 tissue samples that had
      been obtained adjacent to a failed total hip prosthesis from eighty-eight
      patients. The concentration of these particles in the tissue and the size of the
      particles were then analyzed in relation to patient and implant-related
      variables. The number of particles ranged from 8.5 x 10(2) to 5.7 x 10(11) per
      gram of tissue (dry weight). More particles were found adjacent to failed
      titanium-alloy stems that had a cobalt-chromium-alloy modular head and failed
      titanium-alloy-backed cups than were found adjacent to all-cobalt-chromium-alloy
      prostheses. In addition, fewer particles were found adjacent to implants with a
      twenty-eight-millimeter femoral head than were found adjacent to implants with
      other femoral head sizes. Univariate analysis also showed correlations between a
      high concentration of particles and fixation without cement, an implant that had
      been in situ for a long duration, a young patient age, and an initial clinical
      diagnosis of avascular necrosis. Biopsy specimens from the proximal femoral
      membranes had higher concentrations than those from the joint capsules or the
      acetabular membranes. Although only five specimens were obtained directly from
      osteolytic lesions, the concentration of particles in those specimens was higher
      than that in biopsy specimens from other sites. Although many univariate
      correlations were identified, stepwise correlation regression analysis showed
      that the composition of the implant and the size of the modular femoral head were
      most strongly related to the concentration of debris in tissue.

PMID- 8753717
TI  - Abrasive three-body wear of polyethylene caused by broken multifilament cables of
      a total hip prosthesis. A report of these cases.

PMID- 8753718
TI  - Tibial stress fracture after a graft has been obtained from the fibula. A report
      of five cases.

PMID- 8753719
TI  - Monteggia lesion in a child: variant of a Bado type-IV lesion. A case report.

PMID- 8753720
TI  - Absence of avascular necrosis of the humeral head after post-traumatic rupture of
      the anterior and posterior humeral circumflex arteries. A case report.

PMID- 8753721
TI  - Blood transfusion in orthopaedic operations.

PMID- 8753722
TI  - Use of an articulated external fixator for fractures of the tibial plafond.

PMID- 8753723
TI  - Operative treatment of bone overgrowth in children who have an aquired or
      congenital amputation.

PMID- 8753724
TI  - Reflections of a prostate cancer patient.

PMID- 8753725
TI  - Cryosurgical ablation of the prostate: pro.

PMID- 8753726
TI  - Cryosurgical ablation of the prostate: the con side in 1996.

PMID- 8753727
TI  - Enuresis.

PMID- 8753728
TI  - When and how to use buccal mucosal grafts in adult bulbar urethroplasty.
AB  - OBJECTIVES: To evaluate the efficacy of buccal mucosa in the repair of adult
      urethral stricture disease, we report our experience with its use as a
      nontubularized onlay graft during bulbar urethral reconstruction. METHODS: From
      June 1993 to January 1996, 75 men underwent anterior urethral reconstruction for
      stricture disease. Single-stage urethroplasty with an onlay patch graft of buccal
      mucosa was performed in 13 patients with complex, refractory strictures of the
      bulbar urethra. In all cases, a two-team approach was used in which one team
      harvested the graft from the mouth while the perineal team simultaneously exposed
      and calibrated the stricture. RESULTS: The length of buccal mucosa ranged from
      3.5 to 17 cm (average length 6.2). In 8 patients, other reconstructive techniques
      were used concomitantly, including fasciocutaneous penile flap or stricture
      excision and primary anastomosis, depending on the length and severity of the
      scarred area. Median follow-up time was 18 months. Excellent results were
      obtained in all 13 patients, and none has required urethral dilation or
      instrumentation subsequently. Operative time was significantly less than with
      other forms of substitution urethroplasty. CONCLUSIONS: Excellent results can be
      expected when buccal mucosa is used for urethral substitution in men with
      refractory bulbar strictures. For patients with long or dense strictures, buccal
      mucosal grafts may easily be combined with other reconstructive techniques. In
      patients with less complex stricture disease, the reduced operative time of this
      two-team approach may be beneficial.

PMID- 8753729
TI  - Experience with the holmium laser as an endoscopic lithotrite.
AB  - OBJECTIVES: To study, in a clinical series, the safety and efficacy of holmium
      laser energy applied as an endoscopic lithotrite. METHODS: Over a 2-year period,
      patients with urinary tract calculi were treated endoscopically with the holmium
      laser lithotripter, and data were gathered prospectively. Holmium lasers with
      maximum outputs of 15, 25, and 60 W were used. Various low water density, quartz
      fiber delivery systems were developed for specific applications. In addition,
      various combinations of endoscopes and laser fibers were employed. RESULTS: A
      total of 63 patients with 75 calculi were treated. All calculi were cleared
      endoscopically. Minimal variation in laser efficiency was noted with different
      stone compositions, including cystine. Thirty-three of 34 ureteral calculi were
      treated to completion in one sitting (97%). Twenty-nine renal stone burdens were
      treated with the holmium laser, 26 of which were treated solely in a retrograde
      fashion. Of the latter, 23 (88.5%) required only a single sitting. Complications
      from holmium laser energy, including ureteral stricture disease, were not
      encountered in this series. Patients with complex, large stone burdens were
      treated to completion without sequelae. The combination of the actively
      deflectable, flexible ureteroscope and 200-microns fiber facilitated clearance of
      18 lower-pole caliceal calculi. Three patients with partial staghorn stone
      burdens averaging 30 mm in diameter were treated ureteroscopically. Chronic
      urinary infections that were problematic preoperatively completely resolved after
      therapy. All 12 patients who had large bladder calculi with a mean diameter of
      55.8 mm were treated to completion in one sitting. CONCLUSIONS: Holmium laser
      energy is uniquely suited to treat all urinary calculi safely and effectively.

PMID- 8753730
TI  - Transurethral electrovaporization of bladder cancer.
AB  - OBJECTIVES: To describe the use of transurethral electrovaporization in the
      treatment of large superficial bladder tumors. METHODS: The records of 9
      consecutive patients with large superficial bladder tumors treated by
      transurethral electrovaporization were retrospectively reviewed. All patients
      underwent vaporization of superficial tumor with either a grooved or smooth
      rollerball electrode. Tumor characteristics, blood loss, operative time, and
      length of hospital stay were recorded. RESULTS: A total of 12 bladder tumors were
      treated in 9 patients. The mean tumor size was 4.3 cm in diameter and the mean
      operative time was 80 minutes with a range of 60 to 100 minutes. No complications
      were noted and only 1 patient required a transfusion. The mean fall in hematocrit
      was 0.7%. CONCLUSIONS: Transurethral electrovaporization represents a new
      application of electrosurgery that is safe and effective in the treatment of
      large superficial bladder tumors.

PMID- 8753731
TI  - Simple antireflux valve in ileal bladder substitutes: an experimental study in
      dogs.
AB  - OBJECTIVES: To provide a simple, reliable, and easy antireflux valve in ileal
      bladder substitutes. METHODS: Forty centimeters of the terminal ileum were
      isolated. A double-folded pouch was formed using the distal 37 cm, of which the
      proximal 7 cm were left intact to act as a valve. The remaining distal 30 cm were
      detubularized. Suturing at the borders of the valve was performed through linear
      seromuscular grooves created by diathermy burn. The ureters were anastomosed end
      to-side to the supravalvular segment. The pouch was anastomosed to the trigone
      after subtotal cystectomy. The technique was carried out in 10 female mongrel
      dogs. All dogs were evaluated by ascending cystography and excretory urography at
      12 and 20 weeks. Autopsy and histopathologic examination of the valve were
      carried out after the animals were killed at 20 weeks. RESULTS: None of the 10
      animals showed ureteral reflux in ascending cystography. Excretory urography
      revealed a perfect upper tract except in a dog that showed bilateral
      hydroureteronephrosis due to bilateral ureteroileal stenosis. CONCLUSIONS: This
      new valve is technically simple and easy. The procedure is not time consuming,
      and staples are not required. The vascular pedicle is not manipulated. A shorter
      ileal segment is used in this type of valve construction in comparison with that
      required for the intussuscepted valve. This valve appears to be reliable for
      reflux prevention in ileal bladder substitutes.

PMID- 8753732
TI  - Laser prostatectomy: two and a half years' experience with aggressive multifocal
      therapy.
AB  - OBJECTIVES: The aim of this study was to evaluate patient outcome 1 to 2 1/2
      years after aggressive neodymium: yttrium-aluminum-garnet (Nd:YAG) laser
      prostatectomy alone or combined with potassium titanyl phosphate (KTP/532) laser
      therapy. METHODS: In 32 men with symptomatic bladder outlet obstruction caused by
      benign prostatic hyperplasia, Nd:YAG laser energy (40 W) was delivered to six or
      more locations on the prostatic lateral lobes and one or more on the median lobe.
      In a subgroup of 15 of these patients, the prostate was also incised and sculpted
      with KTP/532 laser to create a better channel. RESULTS: In the 32 men, voiding
      parameters improved: mean peak flow rate increased from 10 to 21 mL/s (110%),
      residual volume decreased from 167 to 64 mL (62%), and American Urological
      Association (AUA) symptom score decreased from 24 to 9 (63%). Catheters were
      removed after 3 days. Of the 17 patients treated with the Nd:YAG laser alone, 12
      (70.5%) required recatheterization, whereas only 5 of the 15 (33%) who received
      KTP/532 laser therapy after Nd:YAG treatment required recatheterization (P <
      0.001). In the entire group of 32 patients, complications included predictably
      prolonged retention (14 to 60 days) in 4 patients (12.5%) with hypotonic
      bladders, prolonged dysuria in 4 (12.5%), vesical neck contracture in 2 (6%), and
      significant hematuria in 1; none had incontinence. All 25 sexually active men
      remained potent (100%), but among these patients retrograde ejaculation developed
      in 5 (20%). CONCLUSIONS: Aggressive Nd:YAG laser prostatectomy is safe and
      effective for obstructive prostates up to 70 mL in volume and produces good
      results that are sustained for up to 2 1/2 years. Adjunctive KTP/532 laser
      therapy apparently creates an unobstructed channel more quickly and reduces the
      rate of postoperative retention, but it does not alter other voiding parameters.

PMID- 8753733
TI  - Initial human clinical experience with diode laser interstitial treatment of
      benign prostatic hyperplasia.
AB  - OBJECTIVES: To report the initial results of treatment of outlet obstruction
      induced by benign prostatic hyperplasia (BPH) using interstitial laser
      coagulation performed with the Indigo 830 nm diode laser system. METHODS: A group
      of 112 men with lower urinary tract symptoms caused by BPH underwent treatment
      with the Indigo 830 nm laser system between October 1994 and November 1995.
      Patients were assessed prior to treatment and at specified post-treatment
      intervals for symptom score, uroflow, postvoid residual, and prostate volume.
      Adverse events and changes in laboratory parameters were monitored at each post
      treatment visit to investigate safety of the procedure. RESULTS: Symptom score
      decreased from 20.9 at initial measurement to 9.6 at 3 months after procedure and
      7.9 at 6 months. Uroflow rate increased from 8.0 mL/s initially to 15.2 and 14.2
      mL/s at 3 and 6 months, respectively. Residual bladder volumes decreased from 105
      mL initially to 59 and 38 mL at 3 and 6 months, respectively. There were no major
      complications (impotence, sustained incontinence, significant blood loss). Minor
      complications occurred in a small number of patients but were generally
      associated with urinary tract infection in patients with catheters. Three
      patients (2.7%) required retreatment and underwent transurethral resection of the
      prostate. CONCLUSIONS: Interstitial laser coagulation using an 830-nm diode laser
      system appears to be a promising new treatment, with substantial improvements in
      objective and subjective parameters of obstruction and a favorable side-effect
      profile.

PMID- 8753734
TI  - Transurethral enzymatic ablation of the prostate: canine model.
AB  - OBJECTIVES: The purpose of this study was to investigate the toxicity and
      potential usefulness of transurethral prostatic injection of a collagenase-based
      solution in treating benign prostatic hyperplasia in dogs. METHODS: The injected
      solution contained collagenase, hyaluronidase, Triton X-100, and gentamicin.
      Twenty-one dogs were randomly divided into three groups for transurethral
      prostatic needle injection: two treatment groups were observed for 6 and 12 weeks
      and a control group was observed for 12 weeks. Laboratory studies, clinical
      monitoring, and complete postmortem examination were performed in all animals.
      RESULTS: Gross hematuria was noted in all dogs for a mean of 4 days after
      injection. No significant postoperative morbidity was noted. There were no
      significant differences in the values of laboratory tests among the three groups
      except for a mean increase in serum level of aspartate transaminase for treatment
      groups on postoperative day 1; this resolved by postoperative day 7.
      Histologically, all treated prostates had stromal atrophy and cystic acinar
      dilation involving about 30% of the gland without extraprostatic extension of
      these changes. The urethra, bladder, rectum, testicles, kidney, liver, and lungs
      were normal and intact in all animals. CONCLUSIONS: Transurethral injection of
      this enzyme solution creates a predictable, favorable histologic response in the
      canine prostate. The procedure appears safe and warrants further investigation
      for treatment of human benign prostatic hyperplasia.

PMID- 8753735
TI  - Age- and race-specific reference ranges for prostate-specific antigen from a
      large community-based study.
AB  - OBJECTIVES: To analyze the relationship of age and race to prostate-specific
      antigen (PSA) levels among participants in a community-based study. METHODS: A
      total of 77,700 records of men aged 40 to 79 years were analyzed from a
      longitudinal study of PSA conducted during Prostate Cancer Awareness Week 1993
      and 1994. Records from 1994 were not included for men who were tested in 1993.
      All cases of prostate cancer were excluded. Records with outlier PSA values
      greater than 20 ng/mL were eliminated from the analysis (n = 190; 24%). RESULTS:
      Mean PSA values (ng/mL) of 10-year age groups differed significantly (P < 0.0001)
      between each group (ages 40-49, 0.83; 50-59, 1.23; 60-69, 1.83; 70-79, 2.31). In
      each successively older age group, PSA variance increased significantly (P =
      0.0001). Standard deviations (SD) by age group were: 40-49, 0.79; 50-59, 1.33; 60
      69, 1.94; and 70-79, 2.35. Significant differences in mean PSA by race were
      found. Pairwise differences in mean PSA were found between whites and blacks,
      whites and Latinos, blacks and Asians, and Asians and Latinos (P < 0.0001). No
      statistically significant differences in PSA variance between racial groups were
      found. Age-within-race analysis resulted in consistent statistical significance
      when comparing variance among age cohorts in each race. CONCLUSIONS: Age-specific
      PSA reference ranges are a result of the increasing mean PSA and increasing PSA
      variance in successively older cohorts of men. Mean PSA values differ
      significantly by race, but differences in PSA variance do not. The clinical
      significance of race-specific PSA reference ranges has yet to be determined.

PMID- 8753736
TI  - Free, complexed, and total serum prostate-specific antigen concentrations and
      their proportions in predicting stage, grade, and deoxyribonucleic acid ploidy in
      patients with adenocarcinoma of the prostate.
AB  - OBJECTIVES: Nearly half of men with clinically localized prostate cancer are
      understaged. We evaluated whether knowledge of preoperative free prostate
      specific antigen (f-PSA), complexed (c-PSA), and total (t-PSA) concentrations or
      the ratios thereof (f-PSA/t-PSA, c-PSA/t-PSA, and f-PSA/c-PSA) could improve upon
      the staging of prostate cancer when compared with standard PSA testing (t-PSA).
      In addition, we examined their associations with tumor grade and deoxyribonucleic
      acid (DNA) ploidy. METHODS: Two hundred ninety patients with prostate cancer, 178
      (61%) of whom were treated with radical prostatectomy, formed the study group.
      RESULTS: Although there were significant differences in the f-PSA concentrations
      with respect to clinical stage, considerable overlap in PSA levels among the
      clinical substages was observed. Statistically significant differences but weak
      correlations were observed between the individual f-PSA, c-PSA, and t-PSA
      concentrations with regard to pathologic stage (organ-confined versus
      extraprostatic) and grade. No significant relationship, however, was observed
      with the three ratios. Higher PSA values were not always associated with a
      pathologic stage of pT3 or greater, and lower levels did not ensure that a tumor
      was organ-confined. Only a slight association was observed between c-PSA and t
      PSA levels and DNA ploidy. No significant relationship was observed between the f
      PSA levels as well as the three ratios with regard to DNA ploidy. A statistically
      significant improvement in predicting pathologic stage was observed when
      combining knowledge of preoperative t-PSA concentration with the c-PSA/t-PSA
      ratio. However, the area under the receiver operator characteristic curves was
      only slightly increased; as such this combination was of limited clinical
      utility. CONCLUSIONS: Statistically significant but weak correlations were
      observed between the molecular forms of PSA and stage, grade, and DNA ploidy. The
      significant overlap in f-PSA and c-PSA values among all stages, grades, and
      ploidy values precluded any useful predictive information for the individual
      patient. As such, preoperative knowledge of f-PSA and c-PSA values and the three
      ratios provided no additional diagnostic information over standard PSA (t-PSA)
      values alone.

PMID- 8753737
TI  - Correlation of clinical and pathologic factors with rising prostate-specific
      antigen profiles after radical prostatectomy alone for clinically localized
      prostate cancer.
AB  - OBJECTIVES: To better identify factors affecting prostate-specific antigen (PSA)
      level elevation after radical prostatectomy alone in men with clinical Stage T1-2
      prostate cancer, we have reviewed our experience in the PSA era with 337 cases.
      The identification of these factors permits better understanding of the impact of
      case selection on treatment outcome in prostate cancer. METHODS: The charts of
      all patients treated with radical prostatectomy alone between 1987 and 1993 were
      reviewed. Patients with clinical Stage T3 disease, without preoperative Gleason
      scores or PSA levels, with synchronous bladder cancer, and who received adjuvant
      or neoadjuvant therapy were excluded. The distribution of cases by pretreatment
      PSA levels was as follows: 4 ng/mL or less (16%); greater than 4 to 10 ng/mL
      (48%); greater than 10 to 20 ng/mL (22%); and greater than 20 ng/mL (14%). The
      median pretreatment PSA level for the entire group was 8 ng/mL. Only 26 patients
      (8%) had pathologically positive pelvic lymph nodes. The overall margin
      involvement rate was 43%. Margin involvement rates increased with increasing
      preoperative PSA levels. One hundred eighty-two patients (54%) had surgical
      Gleason scores of 7 or higher and 208 (62%) had extracapsular extension. The
      median follow-up time was 36 months. RESULTS: The 3- and 5-year relapse-free
      survival (RFS) rates were 74% and 61%, respectively, with relapse being defined
      as either a clinically detectable recurrence or detectable/rising PSA levels.
      Among preoperative factors, PSA level was the only independent factor predicting
      relapse (P = 0.006); the 5-year RFS was 89% in patients with preoperative PSA
      levels of 4 ng/mL or less; 62% for PSA level of 4 to 10 ng/mL; 56% for PSA level
      to 10 to 20 ng/mL; and 26% for a PSA level greater than 20 ng/mL. Among
      pathologic parameters, margin involvement was the most potent independent factor
      predicting relapse (P < 0.001), followed by Gleason score (P = 0.002) and
      capsular penetration (P = 0.006). The 5-year RFS rates for margin-positive versus
      margin-negative patients were 37% versus 80%, respectively (P < 0.001). With
      pretreatment PSA levels of 10 ng/mL or less, lymph node involvement was seen in
      3%, and margin involvement in 36%; the 5-year RFS rate was 71%. With pretreatment
      PSA levels of greater than 10 ng/mL, lymph node involvement was seen in 16%, and
      margin involvement in 57%; the 5-year RFS rate was 42%. However, patients with an
      initial PSA level greater than 10 ng/mL and positive margins had a 5-year RFS
      rate of 22% versus 73% in patients with a PSA level of 10 ng/mL or less or
      negative margins (P < 0.001). All clinical relapses were accompanied by a rise in
      PSA. In patients manifesting a clinical recurrence, PSA elevations preceded
      clinical recurrences by an average of 15 months (range 0 to 71). Only 34 cases
      (10%) had clinical failures within 5 years. CONCLUSIONS: Pretreatment PSA is the
      most potent clinical factor independently predicting biochemical relapse. The
      great range in the relapse-free survival rates predicted by preoperative PSA
      levels demonstrates the importance of pretreatment PSA levels in case selection.
      Gleason score, extracapsular extension, and surgical margin involvement are also
      independent predictors of biochemical relapse. Achieving negative margins, even
      in relatively advanced disease, provides excellent long-term local control.

PMID- 8753738
TI  - p53 expression, proliferation marker Ki-S5, DNA content and serum PSA: possible
      biopotential markers in human prostatic cancer.
AB  - OBJECTIVES: The biology of prostate cancer is poorly understood. Despite
      established prognostic criteria, a confident prediction of the clinical outcome
      is not always possible. Therefore, additional and more precise information is
      highly desirable. In the present study, we compared potential biologic markers
      with the laboratory, clinical, and histopathologic parameters of prostate
      specific antigen (PSA) level, tumor stage, and tumor grade. METHODS: Paraffin
      embedded material from 62 radical prostatectomies for prostate carcinoma was
      examined immunohistochemically using monoclonal antibody Ki-S5 to determine the
      tumor growth fraction and antibody DO-1 to assess p53 protein overexpression.
      Deoxyribonucleic acid-ploidy was analyzed by flow and image cytometry.
      Preoperative PSA levels were assessed by standard method. The tumors were
      categorized according to the Gleason grading system and staged postsurgery after
      the TNM classification. RESULTS: The p53 expression, proliferation rate (Ki-S5),
      and rate of aneuploidy correlated closely with stage (P < 0.05) and Gleason score
      (P < 0.01). However, divergences were occasionally observed. The ploidy status
      correlated closely with proliferative activity and p53 expression. Conversely, no
      correlation was seen between these parameters and serum PSA content, the latter
      being significantly associated with the tumor stage alone. CONCLUSIONS: The
      results characterize proliferation marker Ki-S5, p53 expression, and ploidy
      status as tumor biopotential markers, whereas PSA provides diagnostic
      information. Use of these investigative methods promises to provide additional
      information relevant in prognosis and therapy selection. Nonetheless, their
      precise prognostic value will have to be established in further studies.

PMID- 8753739
TI  - Maintaining quality of care and patient satisfaction with radical prostatectomy
      in the era of cost containment.
AB  - OBJECTIVES: To determine the effect of shortened hospital stay after radical
      retropubic prostatectomy on costs, adverse surgical outcomes, and patient
      satisfaction. METHODS: The effect of changes in preoperative counseling,
      perioperative care, and analgesic management on hospital length of stay; mean
      cost per case and cost per hospital day; and 30-day complication, hospital
      readmission, and mortality rates were analyzed for a consecutive sample of 374
      patients undergoing radical prostatectomy between July 1989 and November 1995.
      Satisfaction with length of stay, analgesic regimen, and surgical outcome was
      assessed in a random subset of 150 patients by anonymous questionnaire. RESULTS:
      Length of stay (LOS) was shortened from a median 7 to 2 nights after surgery
      during the study (P < 0.0001), whereas the acute complication, 30-day
      readmission, and 30-day mortality rates remained constant. Reducing LOS resulted
      in a 43% decrease in mean cost per case while mean cost per day increased by 22%
      to 35%. Overall patient satisfaction was high, with 83.5% of patients rating LOS
      as "just right" and 89.2% reporting they were "satisfied" or "very satisfied"
      with their pain control after surgery. CONCLUSIONS: Shortened LOS after radical
      retropubic prostatectomy can be accomplished safely and can meet with high levels
      of patient satisfaction while significantly reducing hospital-related costs. The
      potential for further incremental reductions in cost with reductions in LOS to
      less than 2 nights appears to be small, and future efforts at cost reduction for
      this procedure should center on decreasing the intensity of care during
      hospitalization.

PMID- 8753740
TI  - Congenital posterior urethral perineal fistulae: a unique form of urethral
      duplication.
AB  - Three unique cases of urethral duplication, often referred to as congenital
      posterior urethral perineal fistulae, are presented. Presenting signs and
      symptoms, evaluation, and treatment are discussed, and the literature is
      reviewed. Although labeled as a fistula in the literature, this entity most
      likely represents a distinct type of urethral duplication. A functional dorsal
      urethra separates it from the other forms of urethral duplication.

PMID- 8753741
TI  - Associated urologic anomalies in low imperforate anus are capable of causing
      significant morbidity: a 15-year experience.
AB  - OBJECTIVES: To determine the incidence and morbidity caused by urologic anomalies
      in patients with low imperforate anus. METHODS: The case records and imaging
      studies of 95 patients who underwent surgery for low imperforate anus over a 15
      year period were retrospectively reviewed. Follow-up ranged from 2 to 18 years
      (mean 5.4). RESULTS: Genitourinary abnormalities were seen in 29 patients (31%),
      whereas 10 (11%) had lumbosacral abnormalities. A micturating cystourethrogram
      was performed in 48 patients, 18 of whom were shown to have vesicoureteric reflux
      and 2 of whom required surgical correction. Three additional patients required
      bilateral ureteric reimplantation: 2 had megaureters whereas 1 had bilateral
      ectopic ureters. Four patients had evidence of chronic renal failure; these
      included 1 patient with reflux nephropathy, 2 with bilateral dysplastic kidneys,
      and 1 with neurogenic bladder. The patient with reflux nephropathy underwent
      renal transplantation at the age of 18 years. Two patients had proximal
      hypospadias and 4 had undescended testes. A neurogenic bladder was documented in
      5 children, 4 of whom had lumbosacral abnormalities. One of these had a spinal
      lipoma and required excision of the lipoma and untethering of the spinal cord.
      CONCLUSIONS: We conclude that 30% of patients with low imperforate anus would
      have associated urologic anomalies, several of which are capable of causing
      significant morbidity. Thus, all patients with imperforate anus, whether high or
      low, need to be screened for associated urologic anomalies.

PMID- 8753742
TI  - Local anesthesia for urologic procedures.
AB  - The ability to perform a variety of urologic procedures (urethrotomy, prostate
      surgery, penile prosthesis insertion, and bladder neck suspension) under local
      anesthesia in an outpatient setting is a significant advance in patient care. The
      surgical techniques are described that will allow the urologist to incorporate
      these procedures into practice.

PMID- 8753743
TI  - Cystoscopic changes in interstitial cystitis.

PMID- 8753744
TI  - Recalcitrant gross hematuria secondary to left renal vein hypertension.
AB  - Left renal vein hypertension is a most uncommon and rarely a well-documented
      cause of gross hematuria. We report a case of lateralizing, gross hematuria
      resulting from left renal vein hypertension in an individual with a history of a
      prior Whipple procedure. The diagnosis was suspected at the time of renal
      angiography and proven by renal venography. Complete rapid resolution of the
      hematuria and hypertension was achieved following placement of a left renal vein
      stent.

PMID- 8753745
TI  - Xanthogranulomatous pyelonephritis in a pregnant woman: a case report and review
      of the literature.
AB  - We report a rare case of a 24-year-old woman who presented during her second
      trimester of pregnancy with a presumptive diagnosis of right-sided
      xanthogranulomatous pyelonephritis (XGP). Despite attempted conservative
      management, the patient ultimately required a right nephrectomy without
      complications to either the patient or fetus. Pathology confirmed the diagnosis
      of XGP of the right kidney. Herein, we present a case report and a review of the
      literature concerning XGP and pregnancy.

PMID- 8753746
TI  - Laser ablation of renal pelvic transitional cell carcinoma in a solitary kidney:
      a 9-year follow-up.
AB  - Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser ablation of upper-tract
      urothelial tumors has been well documented in the urologic literature. However,
      the standard treatment of choice remains radical nephroureterectomy with excision
      of a cuff of the bladder for most patients. We report on a patient with recurrent
      superficial transitional cell carcinoma of the renal pelvis in a solitary kidney
      treated with Nd:YAG laser with a 9-year follow-up.

PMID- 8753747
TI  - Giant multilocular cystadenoma of the prostate.
AB  - Giant multilocular prostatic cystadenoma is a rare clinicopathologic entity
      characterized by benign histology and the ability to enlarge massively. The
      lesion may arise from the prostate gland either in continuity with the prostatic
      urethra or separate from it, or it may arise as a lesion distinct from the
      prostate gland. Obstructive voiding symptoms occur in all reported cases. The use
      of preoperative radiographic evaluation, such as magnetic resonance imaging,
      effectively defines the lesion's benign nature and aids in planning surgical
      extirpation.

PMID- 8753748
TI  - Testicular torsion with contralateral vanishing testis.
AB  - An infant with a left hydrocele and nonpalpable right testis had an antenatal
      ultrasonogram showing a left hydrocele and normal right testis. When left
      inguinal hydrocelectomy was performed, extravaginal torsion of the spermatic cord
      and a normal testis was discovered. The right spermatic cord ended in a
      testicular remnant. We propose that this was a case of bilateral antenatal
      torsion that would have resulted in bilateral vanishing testis syndrome had the
      left hydrocele not prevented vascular compromise when antenatal testicular
      torsion occurred. This case gives visible support to the theory that testicular
      remnants are the result of antenatal torsion.

PMID- 8753749
TI  - Perineal abscess after embolization for high-flow priapism.
AB  - High-flow priapism is unusual and is most often due to blunt perineal trauma with
      resultant laceration of the cavernosal artery, creating an arteriocavernosal
      fistula. Although few cases have been reported, the consensus on management
      appears to be embolization of the fistula with autologous clot, alone or in
      combination with Gelfoam. We present a case of high-flow priapism treated in this
      manner. The embolized pseudoaneurysm evolved into an abscess that eventually
      spread to the perineum. The rarity of this entity and the postprocedural
      morbidity are reported.

PMID- 8753750
TI  - Long-segment ureteral replacement with expanded polytetrafluoroethylene grafts.
AB  - OBJECTIVES: Traumatic loss of significant lengths of ureter all too often results
      in nephrectomy when vascularized pedicles of bowel or bladder fail or are not
      available for substitution. Historically, alloplastic replacement of ureters has
      failed due to obstruction, bioincompatibility, or graft migration. This study was
      undertaken to test the performance of ringed expanded polytetrafluoroethylene
      (PTFE) tube grafts as ureteral replacements in a canine model. METHODS: Eight
      female dogs underwent partial ureteral replacement with ringed PTFE tube grafts.
      An involuting anastomosis was used to anchor the graft to the bladder. The dogs
      were followed with intravenous urograms and Whitaker infusion pressure tests for
      up to 12 months. RESULTS: Six of 8 animals (75%) had preservation of excellent
      renal function with normal intravenous urograms and low Whitaker infusion
      pressures. One animal had mild hydronephrosis with an elevated infusion pressure.
      One animal died of spontaneous renal rupture secondary to obstruction at the
      ureteral-graft anastomosis. All other grafts were patent by histologic
      examination without encrustation or infection. CONCLUSIONS: Although not
      suggested as first-line therapy after ureteral loss, expanded PTFE may have a use
      as a prosthetic ureteral replacement in situations where conventional surgical
      therapies are unsuccessful. This material appears to be biocompatible, and the
      technique of bladder anastomosis described here prevented migration of the
      prosthesis.

PMID- 8753751
TI  - Alteration of the hormonal bioactivity of parathyroid hormone-related protein
      (PTHrP) as a result of limited proteolysis by prostate-specific antigen.
AB  - OBJECTIVES: To discover whether the proteolytic activity of prostate-specific
      antigen (PSA) affects the structure and function of parathyroid hormone-related
      protein (PTHrP), as both are abundant components of human seminal plasma.
      METHODS: The ability of PTHrP to act as a substrate was studied by incubating a
      synthetic polypeptide, consisting of 34 amino acid residues of the amino-terminal
      domain of PTHrP, with purified PSA. The incubate was then analyzed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, high-pressure liquid
      chromatography separation, amino-terminal peptide sequencing, and mass
      spectrometry. The physiologic effect of the proteolytic activity of PSA on PTHrP
      was studied by measuring any alteration in PTHrP (1-34)-induced elevation of
      cyclic adenosine monophosphate (cAMP) production by UMR-106 rat osteosarcoma
      cells in culture. All cell culture experiments were performed with PSA and PTHrP
      (1-34) at physiologic concentrations. RESULTS. Our data show that PSA
      proteolytically cleaves PTHrP (1-34) after either residue 22 or 23, generating
      three peptide fragments. Both cleavages occur carboxy terminally of a
      phenylalanine residue. The cAMP production in rat osteosarcoma cells, induced by
      the amino-terminal portion of PTHrP (1-34), as a result of its structural
      similarity with parathyroid hormone (PTH), was abated by PSA in a dose- and time
      dependent fashion. In contrast, heat-inactivated PSA had no effect on cAMP
      production. CONCLUSIONS: Our study demonstrates that PTHrP is a substrate for
      PSA. The cleavage of the amino-terminal portion of PTHrP completely disrupts its
      ability to interact with the PTH/PTHrP receptor and thus inhibits its PTH-like
      activity. The proteolytic processing of PTHrP by PSA may play an important role
      in the post-translational/post-secretional regulation of prostatic PTHrP
      activities, which are believed to include regulation of prostate growth and
      differentiation.

PMID- 8753753
TI  - Effects of androgen deprivation on prostate alpha 1-adrenergic receptors.
AB  - OBJECTIVES: Benign prostatic hyperplasia (BPH), the most common benign tumor in
      men, consists of two components-static (enlargement regulated by androgens) and
      dynamic (smooth muscle contraction through alpha 1-adrenergic receptors [alpha 1
      ARs]). Because medical therapy of BPH involves tissue androgen deprivation, we
      studied the influence of androgen deprivation and replacement on regulation of
      rat ventral prostate alpha 1-ARs. METHODS: Prostate weight, alpha 1-AR density,
      autoradiographic images, histologic features, and cell-specific protein were
      examined before and after castration and androgen replacement. RESULTS:
      Castration decreases ventral prostate wet weight, a process reversed by
      testosterone administration. In contrast, there is an apparent increase in alpha
      1-AR density (29 +/- 4 versus 65 +/- 6 fmol/mg total protein, mean +/- SEM) after
      castration, returning to baseline with testosterone replacement; alpha 1-AR
      density remains constant in control liver membranes. Alpha 1-ARs predominate in
      stroma throughout androgen deprivation therapy. Epithelially derived cells
      decrease (83% to 67%) after castration, resulting in a relative doubling in
      stroma (17% to 33%); the protein content of epithelial and stromal cells remains
      identical. Therefore, prostate-specific increases in alpha 1-ARs appear to result
      from relative increases in the ratio of smooth muscle to epithelium after
      castration rather than from direct upregulation of alpha 1-AR protein.
      CONCLUSIONS: Because alpha 1-AR density does not decrease with androgen
      deprivation, these studies suggest that alpha 1-AR antagonists remain an
      important component in BPH therapy, even when 5-alpha-reductase inhibitors are
      utilized.

PMID- 8753752
TI  - Upregulation of prostate-specific membrane antigen after androgen-deprivation
      therapy.
AB  - OBJECTIVES: To determine the expression of prostate-specific membrane antigen
      (PSMA) before and after androgen-deprivation therapy and to compare PSMA
      expression with prostate-specific antigen (PSA) expression. METHODS: We studied
      specimens from 20 patients with prostate cancer undergoing medical or surgical
      castration or combination androgen-deprivation therapy in whom matched
      pretreatment and post-treatment tissue specimens were available and 16 patients
      in whom only a post-treatment specimen was available. The expression of PSMA and
      PSA in the tissue specimens was determined by immunoperoxidase staining. The
      extent of staining was calculated by multiplying the percent of antigen-positive
      tumor cells by the staining intensity to arrive at a stain index for each
      biomarker. An in vitro study assessed the concentration of PSMA and PSA in
      extracts of LNCaP cells cultured in the presence or absence of androgen as
      determined by immunoassays and Western blot analysis. RESULTS: PSMA reactivity
      was found to be increased in 55% (11 of 20) of post-treatment primary tissues and
      100% (4 of 4) of post-treatment metastatic specimens. In contrast, PSA expression
      was found to be decreased in 70% (14 of 20) of post-treatment primary and 100% (4
      of 4) of post-treatment metastatic specimens. Neither type of androgen
      deprivation treatment nor tissue sensitivity to androgen deprivation appeared to
      influence degree of biomarker expression. PSMA was found to be downregulated and
      PSA upregulated when LNCaP cells were cultured in the presence of testosterone or
      dihydrotestosterone. CONCLUSIONS: The enhanced expression of PSMA in tissues and
      LNCaP cells after androgen deprivation suggests that PSMA is upregulated in the
      majority of prostate carcinomas after androgen treatment. The high expression in
      metastatic tissues strongly suggests that PSMA may be a clinically useful target
      for antibody-and genetic-directed therapy of prostate cancer that recurs after
      androgen deprivation. The mechanism whereby androgens suppress the expression of
      PSMA, and the association of PSMA with the development of hormone-independent
      prostate cancers, will require further study.

PMID- 8753754
TI  - Effective blood volume: an effective concept or a modern myth.

PMID- 8753755
TI  - Mutability and diversity in the biological sciences: a pagan perception of
      nature.

PMID- 8753756
TI  - Multiple viral pathogenicity: another paradigm in medical research?

PMID- 8753757
TI  - The fish-odor syndrome.

PMID- 8753758
TI  - Observations on the Gallic gastric illuminati.

PMID- 8753759
TI  - Legistrothanatry: a new specialty for assisting in death.

PMID- 8753760
TI  - The philosophy of psychopathy.

PMID- 8753761
TI  - Assigning causation in disease: beyond Koch's postulates.

PMID- 8753762
TI  - Moving more closely to acid-base relationships in the body as a whole.

PMID- 8753763
TI  - Rituals and roles in medical practice.

PMID- 8753764
TI  - The discovery of heparin revisited: the peptone connection.

PMID- 8753765
TI  - Cloning and selective expression in brain and kidney of ARNT2 homologous to the
      Ah receptor nuclear translocator (ARNT).
AB  - Arnt2, a new member of the basic-helix-loop-helix transcription factor family,
      was cloned from rat brain cDNAs. Its deduced 712 amino acid sequence displays 63%
      identity with that of the aryl hydrocarbon receptor nuclear translocator (Arnt1)
      that was completely established. Whereas Arnt2 gene expression, established by
      Northern blotting and in situ hybridization histochemistry, occurred selectively
      in brain and kidney, that of Arnt1 was ubiquitous, suggesting that the two
      proteins play distinct roles, presumably via dimerization and DNA binding with
      different partners.

PMID- 8753766
TI  - Stimulation by corticotropin-releasing factor of atrial natriuretic peptide and
      brain natriuretic peptide secretions from cultured neonatal rat cardiomyocytes.
AB  - The new functional role of corticotropin-releasing factor (CRF) in the regulation
      of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) release
      was investigated using cultured neonatal rat cardiomyocytes. Treatment with CRF
      (10(-10)-10(-6) M) resulted in dose- and time-dependent increase in ANP and BNP
      secretion, up to 2.5-fold and 1.8-fold above control values, respectively. The
      effect was significant at 6 hr and persisted for at least 36 hr. The effect of
      CRF (10(-7) M) was partially blocked by alpha-helical CRF(9-41) (10(-7) M), a
      specific CRF receptor antagonist. The effect of CRF (10(-7) M) was not only
      blunted by cAMP-dependent protein kinase A (PKA) inhibitor, H-89 (10(-5) M), but
      also by protein kinase C inhibitors, H-7 (50 microM) and Calphostin C (10(-6) M).
      H-7 (50 microM) and Calphostin C (10(-6) M) alone lowered basal ANP and BNP
      levels. Furthermore, CRF (10(-7) M) stimulates protein synthesis up to 1.2-fold.
      These results indicate that CRF stimulates ANP and BNP secretions through the CRF
      receptor and, at least in part, via PKA activation during cardiac hypertrophy.

PMID- 8753767
TI  - Differential display and cloning of shear stress-responsive messenger RNAs in
      human endothelial cells.
AB  - To investigate the effect of shear stress on endothelial gene expression, we
      performed differential display of mRNAs from cultured human umbilical vein
      endothelial cells either incubated under static conditions or exposed to shear
      stress (15 dynes/cm2) for 6 h in a flow-chamber. Around 4% of the total number of
      mRNAs detected were either up- or down-regulated by shear stress. DNA sequencing
      of some of these shear stress-responsive mRNAs revealed homology of several
      clones to known gene sequences and many other clones for unknown genes. Known
      genes, including those for human laminin B1 chain, H(+)-ATP synthase coupling
      factor 6, lysyl oxidase, myosin light chain kinase, and interleukin-8 receptor,
      were upregulated by shear stress, while the gene encoding NADH dehydrogenase was
      down-regulated. The present results suggest that shear stress can change the
      expression of numerous genes in endothelial cells, far more than reported to
      date, and that mRNA differential display is quite useful for cloning known and
      unknown shear stress-responsive genes.

PMID- 8753768
TI  - Distribution of platelet activating factor receptor mRNA along the rat nephron
      segments.
AB  - Platelet activating factor (PAF) receptor mRNA was semi-quantitated in
      microdissected rat nephron segments by the reverse transcription-polymerase chain
      reaction (RT-PCR). PCR primers were designed from two alternative splicing
      isoforms of rat PAF receptor cDNA; a homologue of human leukocyte PAF receptor
      cDNA (p172) and the other with a unique sequence in the 5'-noncoding region
      upstream of the splice acceptor site (p18). Only the expression of mRNA
      corresponding to p172 was detectable, which was most abundant in the glomerulus,
      followed in order by: proximal convoluted tubule > proximal straight tubule >
      outer medullary and cortical collecting duct, distal convoluted tubule > thick
      ascending limb of Henle's loop. These results suggest the potential physiological
      roles of PAF in the entire renal tubule as well as in the glomerulus.

PMID- 8753769
TI  - Effect of advanced glycosylation end products on the induction of nitric oxide
      synthase in murine macrophages.
AB  - We studied the role of advanced glycosylation end products on the induction of
      nitric oxide synthase in peritoneal mouse macrophages previously exposed to
      modified BSA. A dose-dependent increment in the nitric oxide production induced
      by LPS and IFN-gamma was observed when cell cultures were pretreated with
      modified BSA for 48 hours. In addition, the up regulation of nitric oxide
      production was also time-dependent, being maximal at 24-48 hours. Experiments
      carried out in the presence of neutralizing antibodies to IL-1 and TNF-alpha,
      suggested that up regulation was not due to the capacity of modified BSA to
      induce both proinflammatory signals. The up regulation of nitric oxide production
      was paralleled with an increase in iNOS mRNA.

PMID- 8753770
TI  - Anti-HIV and anti-HBV activity and resistance profile of 2',3'-dideoxy-3'
      thiacytidine (3TC) and its arylphosphoramidate derivative CF 1109.
AB  - A novel membrane-soluble prodrug of the 5'-monophosphate derivative of 3TC
      containing a phenyl group and the methyl ester of L-alanine linked to the
      phosphorus through a phosphoramidate bond with the primary amino moiety
      (designated Cf 1109) was prepared. The 3TC prodrug proved less potent an
      inhibitor of HIV-1 and HIV-2 replication in CEM cell cultures than 3TC, but lost
      only 20-fold antiviral potency in 2'-deoxycytidine kinase-deficient CEM/dCK-
      cells compared with a more than 2,000-fold decrease of activity of 3TC. In
      contrast, 3TC and Cf 1109 proved equally highly effective in inhibiting HBV
      release in supernatants of HBV-transfected Hep G2 2.2.15 cell cultures (50%
      effective concentration approximately 0.02 microM). Both compounds easily
      selected for highly resistant HIV-1 strains at a comparable speed of
      breakthrough. The mutant viruses contained an 184-Ile and/or 184-Val amino acid
      change in their reverse transcriptase. Our data are suggestive for a relatively
      poor delivery of 3TC-MP in the intact CEM cells but a remarkably high delivery of
      3TC and/or 3TC-MP in the intact Hep G2 2.2.15 cells.

PMID- 8753771
TI  - Protein kinase C increases force and slows relaxation in smooth muscle: evidence
      for regulation of the myosin light chain phosphatase.
AB  - To determine if activation of protein kinase C (PKC) participates in the
      molecular mechanism for agonist induced force enhancement, force was measured in
      single beta-escin skinned smooth muscle cells stimulated to contract with Ca2+,
      myosin light chain (MLC) kinase, PKC and microcystin-LR. The constituently active
      fragment of protein kinase C (PKM) increased both force and MLC phosphorylation
      in cells previously stimulated to contract at submaximal Ca2+. For cells
      contracted with saturating Ca2+, PKM stimulation did not increase either force or
      MLC phosphorylation. For contractions stimulated with both PKM and microcystin
      LR, force rose significantly slower than contractions produced by Ca2+ or MLC
      kinase, suggesting that PKM increases force by a decrease in the rate of myosin
      dephosphorylation. Consistent with this hypothesis is the finding that the rate
      of force relaxation was slowed by PKM. This is the first direct demonstration
      that activation of PKC increases force in smooth muscle, and these results
      suggest that in smooth muscle, agonist induced activation of PKC plays a role in
      force regulation via an inhibition of myosin light chain phosphatase activity.

PMID- 8753772
TI  - Application of mRNA differential display to liver cirrhosis: reduced fetuin
      expression in biliary cirrhosis in the rat.
AB  - We here show the application of mRNA differential display to investigate changes
      in gene expression in rat liver cirrhosis and address problems inherent in the
      technique when applied to this complex disease model. A number of differentially
      expressed mRNA species could be identified and two were analyzed in more detail
      here. One was found to derive from a new gene while the other corresponded to
      fetuin, a 41 kDa N-glycoprotein that specifically inhibits tyrosine kinase
      activity of the insulin receptor when phosphorylated. Fetuin expression was
      reduced by 45% in liver cirrhosis induced by bile duct ligation, but not in
      cirrhosis induced by carbon tetrachloride/Phenobarbital, as compared to controls.
      Our results raise the possibility that fetuin plays a regulatory role in the
      proliferation of parenchymal liver cells.

PMID- 8753773
TI  - Association of CD24 with the kinase c-fgr in a small cell lung cancer cell line
      and with the kinase lyn in an erythroleukemia cell line.
AB  - Human CD24 is a highly glycosylated glycosylphosphatidylinositol-linked (GPI
      linked) cell surface protein. GPI-linked proteins are involved in signal
      transduction mediated by members of the protein tyrosine kinase (PTK) family.
      Therefore we studied associated molecules providing the signaling capacity of
      CD24. Lysates of SW2 and K562 cells were analysed for expression of PTK of the c
      src family by Western blotting. We identified c-fgr in SW2 lysates and c-fgr and
      also lyn in K562 lysates. To study a putative association of these PTK with CD24
      we performed immunoprecipitations with the mAb SWA11 directed against CD24.
      Western analysis of the precipitates showed an association of c-fgr with CD24 in
      SW2 cells and lyn in K562 cells. We conclude that either c-fgr or lyn is
      physically associated with CD24 in a cell-type depending manner. An involvement
      of these complexes in signaling phenomenons of CD24 in small cell lung cancer and
      in leukaemias is discussed.

PMID- 8753774
TI  - Activation of phospholipase D in human fibroblasts by ceramide and sphingosine:
      evaluation of their modulatory role in bradykinin stimulation of phospholipase D.
AB  - In the present study the modulatory action of exogenous short-chain ceramide and
      sphingosine on phospholipase D (PLD) activity in young and old human fibroblasts
      was examined. Sphingosine and also ceramide, thus far described as a negative
      modulator of PLD, were able to activate PLD. The stimulatory action of the
      exogenous lipid molecules was mimicked by cell treatment with S.aureus
      sphingomyelinase (SMase). Similar response was elicited by the sphingoid
      molecules in young and old cells. Altered levels of sphingosine and ceramide were
      detected in old fibroblasts confirming that a defect in sphingolipid metabolism
      occurs in cellular senescence. The modulatory role of sphingoid molecules on the
      action of bradykinin (BK) in PLD activation was then evaluated in young and old
      fibroblasts. C6-ceramide or SMase treatment did not affect the action of BK on
      PLD either in young or in old cells, whereas sphingosine further increased PLD
      activity stimulated by BK in young but not in old cells. In addition,
      preincubation with N-oleoylethanolamine, a specific inhibitor of ceramidase, did
      not affect BK action on PLD in young fibroblasts but significantly decreased the
      effect of the peptide in old fibroblasts. These results suggest that a specific
      alteration of BK segnalatory pathway occurs in old fibroblasts, likely involving
      sphingosine formation which may account for the potentiated PLD activity induced
      by the peptide in these cells.

PMID- 8753775
TI  - Relaxed specificity of matrix metalloproteinases (MMPS) and TIMP insensitivity of
      tumor necrosis factor-alpha (TNF-alpha) production suggest the major TNF-alpha
      converting enzyme is not an MMP.
AB  - Tumor necrosis factor-alpha is released from cells by a proteolytic cleavage.
      Previous work suggested that a specific, non-matrix metalloproteinase carries out
      this cleavage, but matrix metalloproteinases have also been implicated. In this
      paper, we report that none of the matrix metalloproteinases tested cleaved
      peptide substrates as specifically as the non-matrix metalloproteinase. A matrix
      metalloproteinase did process tumor necrosis factor-alpha extracted from COS
      cells, but neither tissue inhibitor of metalloproteinases-1 nor -2 blocked tumor
      necrosis factor-alpha processing by human monocytes. Moreover, tissue inhibitor
      of metalloproteinases-1 had at most a partial effect on the in vivo release of
      the cytokine in mice. We conclude that a non-matrix metalloproteinase is the
      major physiological tumor necrosis factor-alpha convertase.

PMID- 8753776
TI  - Cloning of the cDNA for rabbit L-selectin and expression of recombinant protein
      with a kinase target site to facilitate radiolabeling.
AB  - The cDNA encoding rabbit L-Selectin has been cloned from a cDNA library,
      utilizing a PCR-derived probe. It encodes a peptide of 377 amino acids, including
      a signal peptide of 38 amino acids. Sequence analysis demonstrated extensive
      homology with L-Selectin's from other species. Recombinant rabbit L-Selectin
      protein was expressed in eukaryotic cells in a chimeric construct incorporating
      the entire extracellular portion of the protein coding region, a phosphokinase
      target site to allow high activity radiolabeling with 32P, and the constant
      region of the heavy chain of human IgG1 to facilitate purification and detection.
      Amino-terminal peptide sequencing of recombinant L-Selectin confirmed that the
      signal peptide had been removed at the expected site.

PMID- 8753777
TI  - Catalytic properties of the purified rat hepatic cytosolic cholesteryl ester
      hydrolase.
AB  - The purified enzyme hydrolyzed cholesteryl oleate, cholesteryl linoleate, and
      triolein at similar rates over a broad range of concentrations. Hydrolytic
      activity was relatively low with p-nitrophenyl acetate, but much higher with PNP
      esters of the more lipophilic C4-C18 fatty acids, in sharp contrast to microsomal
      esterases which hydrolyze PNP-acetate more efficiently. Zn2+, Cu2+, Cd2+, Hg2+,
      and phenylmethylsulfonyl fluoride inhibited, whereas N-ethyl maleimide and
      iodoacetamide stimulated activity of the pure enzyme. Limited trypsin digestion
      selectively inhibited cholesteryl esterase activity with retention of activity
      toward PNP-octanoate, suggesting involvement of a trypsin-labile loop in the
      lipophilic substrate binding pocket.

PMID- 8753778
TI  - The pleckstrin homology domain of human beta I sigma II spectrin is targeted to
      the plasma membrane in vivo.
AB  - We have examined the in vivo targeting potential of the Pleckstrin Homology (PH)
      domain from human beta I sigma II spectrin using a novel Aequoria victoria green
      fluorescent protein (GFP) fusion vector constructed from a human codon optimized
      cDNA. This vector efficiently expresses both GFP and the GFP spectrin fusion
      protein in COS7 and other cell lines. GFP expressed alone shows only diffuse
      cytoplasmic staining which is not associated with the plasma membrane. In
      contrast the GFP-beta I sigma II spectrin PH domain fusion protein localizes
      under the plasma membrane of transfected COS7 cells in vivo. Fixation of cells
      transfected with GFP alone in -20 degrees C methanol results in the removal of
      all specific fluorescence. In contrast cells transfected with the GFP-beta I
      sigma II spectrin construct and fixed -20 degrees C methanol continue to show
      strong membrane fluorescence, consistent with a role for the spectrin PH domain
      in membrane localization in vivo.

PMID- 8753779
TI  - Decreased expression of a single tropomyosin isoform, TM5/TM30nm, results in
      reduction in motility of highly metastatic B16-F10 mouse melanoma cells.
AB  - Tropomyosin is an actin-associated cytoskeletal protein expressed in muscle and
      non-muscle cells. There are several tropomyosin isoforms, and their cellular
      expression is known to be associated with transformation events caused by
      retroviral infection and chemical mutagens. We found that expression of a low
      molecular weight tropomyosin isoform, TM5/TM30nm, was higher in a high-metastatic
      B16 mouse melanoma cell line, B16-F10, than in B16-F1, a low-metastatic mouse
      melanoma cell line. In order to determine whether this elevated level of
      TM5/TM30nm plays a role in malignant phenotype, B16-F10 cells were transfected
      with recombinant DNA containing antisense rat TM5/TM30nm cDNA linked to the human
      metallothioneinIIa promoter, which is inducible by heavy metals such as zinc and
      cadmium. When the stably transfected clones were treated with ZnSO4, decreased
      expression of TM5/TM30nm and reduction in cell motility, which is thought to be
      an indicator of cellular malignancy were observed. These findings suggest that
      TM5/TM30nm plays a fundamental role in regulating cell motility, which is
      essential for metastasis and invasion of tumor cells.

PMID- 8753780
TI  - Novel azacyclic ureas that are potent inhibitors of HIV-1 protease.
AB  - A series of novel, azacyclic ureas which are highly potent inhibitors of the HIV
      1 protease (IC50 = 4.1 to < 0.5 nM) were synthesized. Aqueous solubilities of
      this series of compounds were improved by incorporating polar functional groups
      at the P1' P2 and P2' positions. These compounds also possess good anti-viral
      activity by inhibition of the cytopathic effect of HIV-13B in MT-4 cells in
      vitro.

PMID- 8753781
TI  - gamma-Linolenic acid supplementation can affect cancer cell proliferation via
      modification of fatty acid composition.
AB  - We examined the effect of gamma-linolenic acid (GLA) supplementation on the
      growth and fatty acid composition of three human tumor cell lines (the
      neuroblastoma CHP-212, the tubal carcinoma TG, and the colon carcinoma SW-620),
      in order to evaluate the relationship between GLA-induced tumor cell death and
      the distribution of fatty acids in tumor cells. At the highest GLA concentrations
      (10 and 20 micrograms/ml), the DNA synthesis was completely abolished; at 5
      micrograms/ml GLA only SW-620 cells did not proliferate, while CHP-212 and TG
      cells showed a residual [3H]-thymidine incorporation. GLA levels were very low in
      cells grown in control medium; GLA supplementation caused a significant
      incorporation of GLA itself in all the cell lines at each concentration. In TG
      and CHP-212 cells, GLA was metabolized, although to a different extent, to dihomo
      gamma linolenic acid and arachidonic acid. SW-620 cells neither elongated nor
      desaturated the incorporated GLA. The highest cytostatic effect was reached when
      GLA was not transformed into its metabolites, suggesting that the GLA toxicity to
      tumor cells is not dependent on metabolites but is due to GLA itself.

PMID- 8753782
TI  - Nuclear matrix localization of annexin V in chicken liver.
AB  - Fractionation of internal matrix proteins from chicken liver nuclei led to the
      isolation of a 32 kDa protein which was identified by partial amino acid sequence
      and immunological analysis as annexin V, an unreported nuclear matrix component.
      Our results showed that this protein is preferentially associated with the
      internal nuclear matrix fraction, since this is the only nuclear fraction where
      the protein can be immunodetected. Immunostaining on cultured cells also revealed
      a nuclear distribution with the exclusion of the nucleolar compartment and an
      association with cytosolic filamentous structures most likely corresponding to
      the cytoskeleton. Moreover, immunostaining on extracted cells to reveal the
      nuclear matrix showed a network-like distribution. Since annexin V has been
      reported as an inhibitor of protein kinase C, its nuclear localization in
      association with the internal matrix, which plays an important role in several
      nuclear processes, indicates its involvement in the regulation of signal
      transduction.

PMID- 8753783
TI  - Phenobarbital induction of cytochrome P4501A1 is regulated by cAMP-dependent
      protein kinase-mediated signaling pathways in rainbow trout hepatocytes.
AB  - Phenobarbital (PB) induces CYP1A1 at the transcriptional level and causes nuclear
      translocation of the aromatic hydrocarbon (Ah) receptor in primary cultures of
      rainbow trout hepatocytes (1). The results from this study suggest that PB
      induction of CYP1A1 in rainbow trout hepatocytes is regulated by cAMP-dependent
      pathways (PKA), whereas TCDD induction is not dependent upon PKA. Epinephrine,
      which increases cAMP levels and activates PKA-dependent pathways, was a potent
      inhibitor of PB induction, while having no effect on TCDD induction of CYP1A1
      gene expression. When PKA-dependent pathways were inhibited, PB induction of
      CYP1A1 gene expression was greatly potentiated, whereas TCDD induction was
      affected to a lesser extent. Inhibitors of calcium-phospholipid-dependent protein
      kinase (PKC) had modest or no effect on PB and TCDD induction of CYP1A1,
      respectively. Whether the relatively weak-to-no inhibition of CYP1A1 in response
      to PKC inhibitors in fish is due to differences in the types and levels of PKC
      isoenzymes, cell permeability, protocol, or the role of PKC in the mechanism of
      CYP1A1 induction in fish remains to be established. PB induced persistent and
      transient increases in the intracellular calcium concentration. This may be an
      important factor regulating PKC which may have a role in PB-mediated induction of
      CYP1A1 gene transcription.

PMID- 8753784
TI  - Reduced microtubule-nucleation activity of tau after dephosphorylation.
AB  - Based on video-enhanced differential interference contrast (DIC) microscopy, we
      developed a small-scale method which is capable of measuring both the lengths and
      the number densities of microtubules (MTs) assembled in vitro. With this method,
      effect of dephosphorylation on the activity of bovine brain tau protein to
      promote the assembly of tubulin at physiological concentration (15 microM) was
      quantitatively analyzed. The MT number density was selectively reduced when tau
      isolated directly in the presence of phosphatase inhibitors (N-tau) was
      dephosphorylated in vitro (DP-tau), without significant changes in the mean MT
      length or the binding affinity toward preformed MTs. Tau obtained from brain MTs
      (MT-tau) also exhibited lower nucleation activity in spite of its high MT-binding
      affinity. The results indicate that nucleation, elongation and MT-binding are
      distinct aspects of tau function which are differentially affected by the
      phosphorylation state of tau.

PMID- 8753785
TI  - Acyl chain dependence of diacylglycerol activation of protein kinase C activity
      in vitro.
AB  - Stimulation of protein kinase C (PKC) activity in lipid vesicles in vitro was
      achieved by pure molecular species of diacylglycerol (DAG), specifically 1
      stearoyl-2-acyl-sn-glycerol substituted with 2-arachidonoyl,2-eicosapentaenoyl or
      2-docosahexaenoyl (SAG, SEG, and SDG, respectively). PKC activity was measured in
      lipid vesicles containing 30 mol% 1-palmitoyl-2-oleoyl-sn-glycerol-3-phospho-L
      serine (POPS), 68-70 mol% 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine
      (POPC), and 0-2 mol% DAG in the presence of 20 microM calcium. Our results
      demonstrate that amplification of PKC activity differs significantly among these
      molecular species of DAG. In particular, SDG at 0.5 mol% is more potent in
      increasing PKC activity than is dioleoylglycerol (DOG), SEG, or SAG, and SAG and
      SDG at 1.0 and 2.0 mol% have similar potencies which are greater than those of
      DOG or SEG. These findings demonstrate that sn-2 substitutions in DAG by specific
      n-3 and n-6 polyunsaturated fatty acids increase the potency of DAG to stimulate
      PKC activity in vitro.

PMID- 8753786
TI  - Synergistic induction of nitric oxide by beta-amyloid and cytokines in
      astrocytes.
AB  - The deposition of beta-amyloid peptides in the brain in form of senile plaque is
      the key event responsible for Alzheimer pathology. Among various mechanisms that
      have been proposed to explain the neurotoxicity of beta-amyloid deposits, a new
      one, recently identified in our laboratory, suggests that beta-amyloid peptides
      may be indirectly toxic for neurons by activating microglial cells to produce NO
      (2). We have investigated if astrocytes, nerve cells that play an important role
      in many brain diseases, also might be involved in a similar mechanism of neuronal
      damage. The results have demonstrated that (1) beta-amyloid peptide (25-35), in
      the presence of IFN gamma or TNF alpha, induces the production of NO in the
      astrocyte cell line C6, while neither cytokine was effective per se; (2) NO
      generation is also synergically induced by beta-amyloid peptide (25-35) in the
      presence of IL-1 beta, the latter being a cytokine able to activate astrocytes
      per se; (3) the effect of beta-amyloid peptide (25-35) is due to the induction of
      the expression of the gene of inducible NO-synthase. These findings suggest that
      astrocytes, activated by deposited beta-amyloid peptides and cytokines, may play
      a role in neuronal damage via the indirect NO mechanism.

PMID- 8753787
TI  - Is receptor cleavage into two subunits necessary for thyrotropin action?
AB  - Unlike the wild-type thyrotropin (TSH) receptor, the chimeric TSH-LH/CG receptor
      TSH-LHR-14 does not cleave into two subunits when cross-linked to [125I]TSH on
      the surface of intact cells. Immunoblotting of TSH-LHR-14 in whole cell
      homogenates demonstrated that only a single chain receptor was detected under
      reducing conditions. TSH-LHR-14, like the A subunit of another chimeric receptor
      (TSH-LHR-10) that does cleave into two subunits, was almost entirely resistant to
      endoglycosidase H, indicating that it contains predominantly complex
      carbohydrate. The fact that TSH-LHR-14 reaches the cell surface where it binds
      TSH with high affinity and transduces a signal indicates that receptor cleavage
      into two subunits is not a prerequisite for TSH action.

PMID- 8753788
TI  - In vivo expression of mRNAs encoding hypoxia-inducible factor 1.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix
      transcription factor that regulates genes whose products play key roles in
      maintaining O2 homeostasis. We have previously demonstrated that HIF-1 mRNA,
      protein, and DNA-binding activity are induced when mammalian tissue culture cells
      are subjected to hypoxia. In this paper, we report our analysis of HIF-1 mRNA
      expression in vivo. We demonstrate expression of HIF-1 alpha and HIF-1 beta
      (ARNT) mRNA in all human, rat, and mouse organs assayed and show for the first
      time that HIF-1 mRNA expression was induced in brain, kidney, and lung when rats
      or mice were exposed to reduced ambient O2 concentrations for 30 to 60 min. The
      ubiquitous in vivo expression of HIF-1 alpha and HIF-1 beta (ARNT) mRNA is
      consistent with the proposed role of HIF-1 in coordinating adaptive
      transcriptional responses to hypoxia.

PMID- 8753789
TI  - Molecular cloning, sequencing, and heterologous expression of a novel zinc
      containing ferredoxin gene from a thermoacidophilic Archaeon Sulfolobus sp.
      strain 7.
AB  - The gene encoding a novel zinc-containing ferredoxin from a hyperthermophilic and
      acidophilic archaeon (archaebacterium) Sulfolobus sp. strain 7 was cloned and
      sequenced. The DNA sequence predicts a 103 residue protein after removal of N
      terminal methionine, which is in good agreement with the results of the protein
      analysis. Surprisingly, the residues responsible for binding a zinc atom were
      conserved among three other thermoacidophilic archaea. A common sequence stretch
      VXGXHXGHX8-17PXXLGXHGTX38-56KXDPV is proposed as a new zinc-binding motif, where
      three histidines and an aspartic acid are ligated to a zinc atom. The ferredoxin
      gene was expressed in Eschericia coli. The recombinant ferredoxin was
      indistinguishable from the protein purified from Sulfolobus sp. strain 7 cells by
      several criteria so far investigated except that the methylation of the 29th
      lysine was suppressed.

PMID- 8753790
TI  - Differential mRNA expression of phospholipase D (PLD) isozymes during cAMP
      induced differentiation in C6 glioma cells.
AB  - GTP gamma S-dependent phospholipase D (PLD) activity time-dependently increased
      during differentiation of rat C6 glioma cells to astrocytic phenotypes induced by
      dibutyryl cyclic AMP (dbcAMP)/theophylline. The changes in PLD mRNA level were
      examined by reverse transcriptase-polymerase chain reaction (RT-PCR) method using
      the degenerate primers designed based on two conserved amino acid sequences in
      PLDs of human and yeast. The amplified three DNA fragments (tentatively termed as
      rPLDa, b, and c) contained the conserved regions present in PLDs of various
      organisms. RT-PCR using non-degenerate primers showed that rPLDa mRNA increased
      within 12h following treatment with dbcAMP, reaching a broad plateau and then
      returned to the initial level at 48h. In contrast, the level of rPLDb mRNA showed
      a concurrent decrease. rPLDc decreased in a time-dependent manner. These results
      suggest that the expression of PLD mRNAs are differentially regulated during
      differentiation in C6 glioma cells.

PMID- 8753791
TI  - Two hypothetical proteins of human aortic adventitia, with Ig kappa, collagenous,
      and aromatic-rich motifs.
AB  - Two of five clones, selected from an expression library of aortic adventitia,
      encode unique hypothetical proteins sharing sequences of Ig kappa, gly/pro rich
      (collagenous) motifs, and aromatic motifs that occur in several proteins of the
      extracellular matrix. Both proteins have a similar domain structure with at least
      8 regions: (1) Ig kappa (84-120 residues in length); (2) ser/thr-rich motif (44
      63); (3) a second Ig kappa motif (9-12); (4) either a possible calcium-binding
      motif or a gly/pro rich sequence (35-43); (5) an aromatic rich sequence (6-7);
      (6) another gly/pro rich sequence (62-72); (7) a third Ig kappa sequence (26-28);
      and (8) a C-terminal 68-70 residue sequence with another aromatic motif.

PMID- 8753792
TI  - Calcium-activated chloride currents and non-selective cation channels in a novel
      cystic fibrosis-derived human pancreatic duct cell line.
AB  - The modulation of ion fluxes across the plasma membrane of epithelial cells is
      central for fluid secretion and absorption. Their disruption can lead to
      pathological states. An example is cystic fibrosis (CF), a disease characterized
      by abnormal functioning of the cystic fibrosis transmembrane conductance
      regulator (CFTR), a cAMP-modulated chloride channel. Here we report the
      characterization of calcium-activated, DIDS sensitive chloride current and non
      selective calcium-activated cation channels in a novel human pancreatic duct cell
      line (YHV-1) derived from a non-delta F508 mutation CF patient bearing a severe
      phenotype. Southern blot analysis of the CFTR gene indicates a distinct
      electrophoretic pattern for the region spanned by exons 15-24, a result
      presumably related to a mutation which has yet to be identified. In contrast to
      large calcium-activated chloride currents there were no cAMP-dependent CFTR-type
      chloride currents. Non-selective cation channels were blocked by intracellular
      ATP and activated by intracellular calcium and cAMP. We propose the cell line YHV
      1 as a suitable model for studying pancreatic ion and fluid secretion alterations
      in CF.

PMID- 8753793
TI  - Enhanced phospholipase D activity and altered morphology in RhoA-overexpressing
      RAT1 fibroblasts.
AB  - Small GTP-binding proteins of the Rho family are implicated in the regulation of
      phospholipase D (PLD). However, few studies have addressed their role in agonist
      stimulated PLD activity in vivo. Stable lines of Rat1 fibroblasts overexpressing
      RhoA were shown to have altered morphology. Moreover, they demonstrated increased
      PLD activity when stimulated with lysophosphatidic acid, platelet-derived growth
      factor, and phorbol ester, compared with vector-transfected cells. However,
      phosphoinositide phospholipase C activity was unaltered by overexpression of
      RhoA. These data indicate a critical downstream role for RhoA in agonist
      stimulated PLD activity in intact cells.

PMID- 8753794
TI  - Protein phosphatase inhibitors potentiate Ca2+/calmodulin-dependent protein
      kinase II activity in rat pancreatic acinar cells.
AB  - Cholecystokinin (CCK) is known to rapidly and transiently increase both [Ca2+]i
      and autonomous CaM kinase II activity in rat pancreatic acini. Because induction
      of autonomous activity may involve intramolecular autophosphorylation, the
      effects of protein phosphatase inhibitors were examined. None of the inhibitors
      tested (okadaic acid, calyculin A, and cyclosporin A) affected basal activity.
      Okadaic acid, a potent inhibitor of PP2A and weaker inhibitor of PP1, increased
      the peak autonomous activity by 30% over the level normally induced by CCK alone,
      while calyculin A, a potent inhibitor of both PP1 and PP2A, showed an even
      greater increase of 97%. Both inhibitors also delayed the decline of autonomous
      activity and calyculin A had a more potent effect than okadaic acid. Cyclosporin
      A, an inhibitor of PP2B, had no effect. The data indicate that PP1 may be
      involved in the dephosphorylation of CaMK II and decline of autonomous activity.

PMID- 8753795
TI  - Prevention of the expression of inducible nitric oxide synthase by aminoguanidine
      or aminoethyl-isothiourea in macrophages and in the rat.
AB  - An enhanced formation of nitric oxide (NO) following the induction of the
      inducible isoform of NOS (iNOS) has been implicated in the pathogenesis of
      circulatory shock and inflammation. This study elucidates the effects of the NOS
      inhibitors aminoethyl-isothiourea (AE-ITU), aminoguanidine (AG), NG-methyl-L
      arginine (L-NMMA) or N omega-Nitro-L-arginine methyl ester (L-NAME) on the
      expression of iNOS protein lipopolysaccharide (LPS) in macrophages and the rat
      (lung homogenates). The expression of iNOS protein was detected by Western blot
      analysis using a specific iNOS antibody. In the absence of LPS, the iNOS protein
      was expressed neither in macrophages nor in the lung. LPS (1 microgram.ml-1)
      resulted in the expression of iNOS protein in macrophages, which was
      significantly inhibited by pretreatment of cells with AE-ITU or AG, but not by L
      NMMA or L-NAME. In addition, LPS (10 mg.kg-1, i.v.) also caused an increase in
      the expression of iNOS protein in lungs obtained from rats at 6 h after LPS,
      which was significantly reduced by treatment of LPS-rats with AE-ITU or AG, but
      not with L-NMMA or L-NAME. Thus, AE-ITU or AG inhibit not only iNOS activity, but
      also the induction of iNOS protein in vitro and in vivo caused by endotoxin.

PMID- 8753796
TI  - Inhibition of the G2/M transition of the cell cycle by methyl-2,5
      dihydroxycinnamate in human lymphoid cells.
AB  - Immortalized human lymphoid cells treated with Methyl-2,5-dihydroxycinnamate
      (MDHC), a stable analog of erbstatin, inhibited the G2/M transition of the cell
      cycle. The MDHC inhibition of the cell cycle was observed at concentrations well
      below the IC50 for the inhibition of the EGF receptor and sufficiently below that
      reported to induce protein cross-linking. The effect of MDHC upon the cell cycle
      is relatively stable, since unlike erbstatin, inhibition of the G2/M transition
      was observed 32 hours following removal of the drug. PHA stimulated human
      peripheral blood mononuclear cells (PBMC) were much less sensitive to MDHC. This
      study shows that MDHC acts on cells lacking an EGF receptor and the target of
      MDHC is involved in promoting progression of the cell cycle.

PMID- 8753797
TI  - Specific orientation of porphyrin at the binding site of catalytic antibody.
AB  - The catalytic antibody which catalyzes insertion of a cupric ion into
      mesoporphyrin bound ferric N-methyl mesoporhyrin and ferric mesoporhyrin to yield
      the respective complexes. The binding affinity of cyanide to the ferric iron in
      the complexes was compared with that of free ferric porphyrins. The results
      indicate that the one side of the porphyrin plane in the complex is thoroughly
      exposed to surrounding solvents and the other side interacts with the protein
      molecule. The cyanide binding suggests the specific orientation of distorted
      porphyrin at the binding site of the antibody.

PMID- 8753798
TI  - Tumour necrosis factor alpha causes retention of activated glucocorticoid
      receptor within the cytoplasm of A549 cells.
AB  - Glucocorticosteroids are the most effective therapy for the suppression of airway
      inflammation. Classically, ligand binding to the inactive cytosolic receptor (GR)
      causes a conformational change enabling nuclear translocation of the active GR
      and alteration in the transcriptional response. We have investigated GR
      transcription factor interactions within the cytoplasm where many transcription
      factors are localized prior to activation. Active DNA binding GR complexes were
      found within the cytoplasm of human lung epithelial cells (A549). Stimulation by
      dexamethasone (1 microM) caused translocation of active GR into the nucleus and
      inhibition of RANTES release. Coincubation of cells with dexamethasone and TNF
      alpha (1 ng/ml) or PMA (0.1 microM) prevented RANTES release and the
      translocation of activated GR to the nucleus without affecting GR levels as
      detected by western blotting. These results suggest that a major site of pro
      inflammatory cytokine action may be within the cytoplasm of steroid-responsive
      cells acting via prevention of the GR translocation into the nucleus.

PMID- 8753799
TI  - 1 alpha,25(OH)2 vitamin D3-mediated stimulation of outward anionic currents in
      osteoblast-like ROS 17/2.8 cells.
AB  - 1 alpha,25-dihydroxyvitamin-D3 [1 alpha,25(OH)2D3] is known to potentiate in
      osteoblast-like rat osteosarcoma cells (ROS 17/2.8) the influx of Ca2+ through
      voltage-activated L-type Ca2+ channels. In the present study, by means of the
      whole-cell patch-clamp technique, we found that physiological concentrations of 1
      alpha,25(OH)2D3 (5-5000 x 10(-11) M) also stimulate, in a dose-dependent manner,
      outwardly rectifying anionic currents over the course of 1-5 minutes. These
      currents, recorded in the presence of 130 mM glutamate or approximately 140 mM C1
      in the external solution, were blocked by 200 microM DIDS, a stilbene derivative
      selective for C1- channels. We conclude that, in addition to the already known
      effects of 1 alpha,25(OH)2D3 on Ca2+ channels, the hormone also enhances in ROS
      17/2.8 cells an outward anion conductance. This is the first report concerning
      activation of anion channels by 1 alpha,25(OH)2D3.

PMID- 8753800
TI  - N-ethoxycarbonyl-D-phenylalanyl-L-prolyl-alpha-azalysine p-nitrophenyl ester: a
      novel, high selective and optimal chromogenic active site titrant for human and
      bovine alpha-, beta- and gamma-thrombin.
AB  - The serine proteinase catalyzed hydrolysis of N-ethoxycarbonyl-D-phenylalanyl-L
      prolyl-alpha-azalysine p- nitrophenyl ester (Eoc-D-Phe-Pro-azaLys-ONp) was
      investigated at pH 6.2 and 21.0 degrees C. The results are consistent with the
      minimum three-step catalytic mechanism. The acylation step is rate limiting for
      human (Lys 77 species) and porcine plasmin, and for bovine beta-trypsin, the
      deacylation rate being limiting, on the other hand, for human and bovine alpha-,
      beta- and gamma-thrombin. Moreover the M(r) 33,000 species of human urokinase and
      the neuraminidase-treated porcine pancreatic beta-kallikrein-B do not catalyze
      the hydrolysis of the tripeptide. According to the specificity properties of the
      serine proteinases considered. Eoc-D-Phe- Pro-azaLys-ONp shows the
      characteristics of a novel, high selective and optimal chromogenic active site
      titrant for human and bovine alpha-, beta- and gamma-thrombin.

PMID- 8753801
TI  - STAT-like DNA-binding activity in Spodoptera frugiperda cells.
AB  - Nuclear extracts from Spodoptera frugiperda (Sf9) cells were shown to contain a
      factor binding to DNA elements with gamma interferon activated site-like
      sequences. The DNA-binding activity was shown to be dependent on tyrosine
      phosphorylation. Hydrodynamic characterization of this entity revealed a Stokes
      radius of 8.4 nm and a sedimentation coefficient of 5.9 S. The molecular weight
      was calculated to 209,000. Estimated frictional (f/to) and axial (a/b) ratios
      indicated an elongated structure of this DNA-binding entity. This DNA-binding
      factor could represent a dimer of a Sf9 homolog to the mammalian signal
      transducers and activators of transcription.

PMID- 8753802
TI  - Hammerhead ribozyme-mediated inhibition of telomerase activity in extracts of
      human hepatocellular carcinoma cells.
AB  - Telomerase, a ribonucleoprotein that directs the synthesis of telomeric DNA
      repeats and compensates for the telomeric losses that occur with cell division,
      is absent from most mortal cells but is present in immortal cells. Telomerase
      activity is thought to be essential for continuous cell division as seen in
      malignant tumor cells, and its inhibition could be a strategy for anti-cancer
      therapy. We prepared a hammerhead ribozyme (teloRZ) directed against the RNA
      component of human telomerase and tried to find if it could serve as an inhibitor
      of telomerase. TeloRZ showed a specific cleavage activity against a synthesized
      portion of the telomerase RNA component used as the substrate. Furthermore, when
      added to cell extracts from HepG2 or Huh-7, human hepatocellular carcinoma
      derived lines, teloRZ inhibited the telomerase activity in both. These findings
      support the potential application of ribozymes capable of telomerase inhibition
      as new therapeutic agents directed against immortalized cancer cells.

PMID- 8753803
TI  - EPR and laser flash photolysis studies of the reaction of nitric oxide with water
      soluble NO trap Fe(II)-proline-dithiocarbamate complex.
AB  - Diethyl-dithiocarbamate (DETC) chelating ferrous iron is used during EPR
      detection of nitric oxide (.NO) as a precursor of spin traps for the
      quantification of released .NO both in vitro and in vivo. This method is based on
      the high affinity of water insoluble iron-dithiocarbamate complexes towards .NO.
      The nitrosyl-iron-dithiocarbamate complex NOFe(DETC)2 is formed with
      characteristic triplet EPR spectrum. In the present paper we have studied the
      reaction of water soluble Fe(II)-proline-dithiocarbamate complex, Fe(PDTC)2, with
      nitric oxide using both EPR spectroscopy and laser flash photolysis. It has been
      found that the treatment of the Fe(PDTC)2 complex either by authentic .NO
      dissolved in aqua buffer solutions or by different .NO donors results in the
      quantitative appearance of an EPR signal of a stable mononitrosyl complex
      NOFe(PDTC)2 with a g-factor giso = 2.04 and a hyperfine splitting constant aN =
      12.5 G. The laser flash photolysis method has been used to study the kinetics of
      .NO trapping by Fe(PDTC)2. Nitric oxide release from a light sensitive .NO donor,
      piridazinofuroxan, was induced by a short flash of UV light generated by a XeCl
      eximer laser. The rate constant of the reaction of .NO with Fe(PDTC)2 was found
      to be (1.1 +/- 0.3).10(8) M-1s-1, manifesting a high efficiency of .NO trapping
      by Fe(PDTC)2.

PMID- 8753804
TI  - The opposing effects of retinoic acid and phorbol esters converge to a common
      response element in the promoter of the rat cholesterol 7 alpha-hydroxylase gene
      (CYP7A).
AB  - The activity of the rat CYP7A/luciferase reporter gene was increased five-fold by
      all-trans retinoic acid (atRA) or 9-cis retinoic acid (9cRA) in transient
      transfection assay in HepG2 cells. Cotransfection with retinoid X receptor (RXR)
      stimulated the promoter activity in the absence of ligand, however, addition of
      atRA inhibited the transcriptional activity. Cotransfection with retinoic acid
      receptor (RAR) did not have much effect on CYP7A promoter activity. The CYP7A
      promoter, when linked upstream to the SV40/ luciferase reporter gene, strongly
      repressed the phorbol 12-myristate 13-acetate (PMA)-stimulated SV40/ luciferase
      reporter gene activity. The regions conferring the effects of RA and PMA were
      mapped to nt-176/ -117 and nt-148/-129, respectively. Several direct repeats of
      hormone response element (AGTTCA) in this region are required for RA response. AP
      1 like sequences are located within the region responding to both RA and PMA.
      Site-directed mutagenesis of the AP-1 site abolished the effects of both RA and
      phorbol esters. Retinoic acid effect was antagonized by PMA. Moreover,
      cotransfection of Fos and Jun expression vectors blunted the stimulatory effect
      of retinoic acid on the CYP7A/luciferase gene activity. Therefore, effects of two
      different signal transduction pathways converge to a common response element.
      This regulatory cross-talk may be involved in bile acid repression and regulates
      CYP7 gene transcription in the liver.

PMID- 8753805
TI  - Inhibition of insulin-induced chondrogenic differentiation of embryonic carcinoma
      cells by a teratogenic compound YM9429.
AB  - A teratogenic compound cis-1-[4-(p-menthane 8-yloxy)phenyl]piperidine (YM9429)
      induces cleft palate selectively in rat fetuses. The effect of YM9429 on
      chondrogenic differentiation was investigated using mouse embryonic carcinoma
      ATDC5 cells that produce chondrocyte specific extracellular matrix upon insulin
      stimulation. YM9429 at concentrations that showed no growth-inhibitory effect on
      logarithmic proliferating cells suppressed insulin-mediated increases in Alcian
      blue staining and expression of type II collagen almost completely. Under the
      identical conditions, insulin-stimulated cell growth was only partially blocked
      by the compound. The early response genes such as c-fos and c-jun were induced by
      insulin even in the presence of YM9429. On the other hand, YM9429 inhibited
      accumulation of cAMP during the differentiation process. These results indicate
      that YM9429 selectively inhibits in vitro chondrogenic differentiation of ATDC5
      cells.

PMID- 8753806
TI  - Pre-conditioning of smooth muscle cells via induction of the heat shock response
      limits proliferation following mechanical injury.
AB  - Arterial smooth muscle cell (SMC) proliferation is a significant component of
      post-angioplasty restenosis. We evaluated whether pre-conditioning of SMCs, via
      induction of the heat shock response prior to actual physical injury, would
      result in an alteration in cell proliferation following injury. Rat aortic SMCs
      were pretreated with either chemical or thermal heat shock inducers and then
      subjected to scrape-wound injury in vitro. Cell proliferation at 24 hrs was
      measured via 3H-thymidine (Tdr) incorporation and compared with scrape wounded
      unstressed controls. A significant decline in cell proliferation post scrape
      wound injury was observed for both chemical and thermal heat shock pre
      conditioned cultures, compared to untreated controls. Increased expression of
      heat shock protein 72 was confirmed serially throughout the 24 hr study period
      for both chemical and thermal inducers. Despite reduced proliferation heat
      shocked cells remained viable as evidenced by fluorescent cell viability assay
      and preserved migration. Pre-conditioning of SMCs through induction of the heat
      shock response prior to physical injury may be a useful approach to limit
      aggressive proliferation observed with mechanical revascularization injury.

PMID- 8753807
TI  - Isolation of cDNA for a novel human protein KNP-I that is homologous to the E.
      coli SCRP-27A protein from the autoimmune polyglandular disease type I (APECED)
      region of chromosome 21q22.3.
AB  - We have isolated cDNA clones for a novel human protein KNP-I from fetal brain and
      bone marrow cDNA libraries. Northern blot analysis indicated that the KNP-I gene
      is ubiquitously expressed in various human tissues. Significant homology of the
      KNP-I protein with Escherichia coli anti-sigma cross-reacting protein (SCRP-27A)
      (44% identity) and zebrafish (Brachydanio rerio) esl protein (49% identity)
      suggested that the KNP-I protein may be involved in a basic cellular function.
      Genomic sequencing revealed that the KNP-I gene consists of seven exons spanning
      12 kb. Exon 5 was involved in alternative splicing. The KNP-I gene was mapped
      between D21S1460 and D21S25 on human chromosome 21q22.3, 26 kb distal to a Not 1
      site of D21S1460. Thus, this novel KNP-I gene could be a candidate gene for
      autoimmune polyglandular disease type I (APECED) and other disorders mapped to
      this region.

PMID- 8753808
TI  - The immune stimulatory protein 90K increases major histocompatibility complex
      class I expression in a human breast cancer cell line.
AB  - 90K is a widely expressed, secreted 90 kDa human serum protein found both in
      normal individuals and at elevated levels in the serum of cancer patients.
      Functional characterization revealed stimulatory effects of 90K on immune defense
      systems, such as natural killer and lymphokine-activated killer cell activity.
      Recently, experiments have shown that 90K expression in several tumor cell lines
      inversely correlates with tumor formation in athymic mice. The mechanism of this
      tumor suppressive effect is unknown. In the present study, we evaluated the
      ability of 90K to affect the expression of MHC class I molecules in the human
      breast cancer cell line EVSA-T. Treatment with 90K (1-50 micrograms/ml) caused
      the levels of MHC class I expression to increase approximately sixfold above
      control levels, as measured by flow cytometry. IFN-gamma was used as a positive
      control and yielded increased expression of MHC class I molecules approximately 8
      times over control levels. These data demonstrate that 90K can directly affect
      the expression of molecules that are engaged in protective antitumor response.

PMID- 8753809
TI  - The natural product noformycin is an inhibitor of inducible-nitric oxide
      synthase.
AB  - Inducible-Nitric oxide synthase (iNOS, EC 1.14.13.39) catalyzes the formation of
      nitric oxide (NO) and L-citrulline from L-Arg. NADPH and dioxygen. The natural
      product, (-)-noformycin was found to be a potent, competitive inhibitor of
      recombinant human iNOS with respect to L-Arg with a Ki = 1.3 +/- 0.3 microM. The
      reversible binding of noformycin caused a high spin type I spectral perturbation
      of the iNOS heme group with a Kd = 1.5 +/- 0.2 microM. These results demonstrate
      that natural products may be a useful source for inhibitors of NO-biosynthesis.

PMID- 8753810
TI  - A RING finger motif regulates transforming activity of the rfp/ret fusion gene.
AB  - The rfp/ret transforming gene was generated by DNA rearrangement which occurred
      during transfection of NIH 3T3 cells. The amino-terminal half of Rfp with a RING
      finger motif was fused to the truncated Ret receptor tyrosine kinase, leading to
      a transforming sequence, Rfp/Ret. In the present study, to elucidate the
      importance of a RING finger motif for its transforming activity, we mutated
      cysteine or histidine residues present in the motif that are believed to be
      crucial for the tertiary structure of the protein. Substitution of Cys-16, Cys
      31, or His-33 markedly decreased the transforming activity of Rfp/Ret. These
      mutations also resulted in a striking decrease of tyrosine phosphorylation of the
      mutant proteins in transfectants. In contrast, mutations of Cys-118 or His-124 in
      the second cysteine/histidine-rich motif (called B box) of Rfp/Ret did not affect
      its activity. These results thus indicated that the RING finger structure is
      critical for the full transforming activity of Rfp/Ret.

PMID- 8753811
TI  - Slim defines a novel family of LIM-proteins expressed in skeletal muscle.
AB  - We have assembled the complete protein sequence of the skeletal muscle LIM
      protein SLIM by aligning overlapping cDNA sequences. These cDNA sequences were
      identified from our own sequencing and from BLASTn searches of non-redundant cDNA
      databases. The predicted SLIM protein sequence included four LIM-domains and a
      novel single zinc finger domain located in the N-terminal region. Similar
      sequences to SLIM were identified and termed SLIM2 and SLIM3. The SLIM3 cDNA
      sequence was identified subsequently as a partial sequence of the of the LIM
      protein DRAL. The number and spacing of the LIM domains was common to all three
      protein sequences. The mRNA for each protein was detected in human masseter
      muscle RNA by Northern analysis. We suggest that these proteins belong to a novel
      family of LIM proteins that are expressed in human skeletal muscle.

PMID- 8753812
TI  - Production of granulocyte colony-stimulating factor by THP-1 cells in response to
      retinoic acid and phorbol ester is mediated through the autocrine production of
      interleukin-1.
AB  - The human monocytic leukemic cell line, THP-1, which differentiates toward
      macrophages in response to phorbol 12-myristate 13-acetate (PMA) was investigated
      for its ability to produce granulocyte colony-stimulating factor (G-CSF). G-CSF
      protein was neither produced during PMA-induced differentiation nor in response
      to retinoic acid (RA) alone. However, when combined, PMA and RA synergistically
      stimulated G-CSF production with optimal effect observed at 10(-7)M for both PMA
      and RA. The synergistic interaction between PMA and RA on G-CSF production
      appeared to be mediated primarily through production of interleukin-1 beta (IL-1
      beta) since neutralization of IL-1 beta activity inhibited about 80% of G-CSF
      production. It has been previously reported that IL-1 potently synergizes with RA
      to stimulate G-CSF production by THP-1 cells pretreated with PMA Using synthetic
      ligands to RA receptors (RAR) and retinoid X receptors (RXR) that selectively
      bind and activate RAR-RXR and RXR-RXR dimers respectively, we showed that the
      ability of RA to synergize with IL-1 was signaled through RAR-RXR heterodimer
      pathway. Finally, we demonstrated that RA can also enhance IL-1-induced G-CSF
      production in primary monocytes of human peripheral blood.

PMID- 8753813
TI  - Promoter usage determines tissue specific responsiveness of the rat acetyl-CoA
      carboxylase gene.
AB  - The acetyl-CoA carboxylase gene contains two promoters, PI and PII which generate
      multiple mRNA forms. We have used the reverse transcription-polymerase chain
      reaction to investigate tissue specific promoter usage in rats either fed a
      standard chow diet, starved for 48 h, or starved and then refed a high
      carbohydrate, low fat diet. Expression of PII-generated mRNAs was seen in all
      tissues examined and was not dramatically changed by food removal or refeeding.
      PI-generated mRNAs were expressed at variable levels in a narrower range of
      tissues and were regulated by these dietary manipulations. Thus only the PI
      promoter is responsive to diet and the ability of a tissue to use this promoter
      determines whether it can alter fatty acid synthesis in response to nutritional
      challenges.

PMID- 8753814
TI  - Characterization of RNA binding activity and RNA helicase activity of the
      hepatitis C virus NS3 protein.
AB  - The Hepatitis C Virus (HCV) NS3 protein has RNA binding activity, RNA-stimulated
      NTPase activity, and RNA helicase activity. The RNA binding activity of the C
      terminal domain of the HCV NS3 protein is less sensitive to pH, KCl, and MgCl2
      than NTPase and the RNA helicase activity. The overall order of the binding of
      homoribopolymer for the NS3 protein was poly(U) > > poly(A) > poly(G), poly(C).
      The minimal RNA binding size of the HCV NS3 protein was determined using a gel
      retardation assay and is estimated between 7 nt and 20 nt. The HCV RNA helicase
      unwinds RNA/DNA heteroduplexes as well as RNA/RNA duplexes and it catalytically
      translocates in the 3' to 5' direction.

PMID- 8753815
TI  - Novel anti-carcinogenic activity of an organosulfide from garlic: inhibition of H
      RAS oncogene transformed tumor growth in vivo by diallyl disulfide is associated
      with inhibition of p21H-ras processing.
AB  - In this study, we report a novel anticarcinogenic activity of an organosulfur
      compound from garlic, diallyl disulfide (DADS). DADS treatment significantly
      inhibited the growth of H-ras oncogene transformed tumors in nude mice. As
      compared to controls, the appearance of tumors was also delayed markedly by oral
      administration of DADS. The inhibition of tumor growth by DADS treatment
      correlated with the inhibition of p21H-ras membrane association in the tumor
      tissue. The levels of membrane associated p21H-ras were markedly lower in the
      tumor tissues of DADS treated mice as compared to controls. An opposite trend,
      however, was evident for cytosolic p21H-ras. Furthermore, DADS treatment resulted
      in a significant inhibition of hepatic as well as tumoral 3-hydroxy-3
      methylglutaryl coenzyme A reductase activity. These results indicate that DADS
      suppresses the growth of H-ras oncogene transformed tumors in nude mice by
      inhibiting the membrane association of tumoral p21H-ras.

PMID- 8753816
TI  - Dialysis of inositol 1,4,5-trisphosphate induces inward currents and Ca2+ uptake
      in frog olfactory receptor cells.
AB  - Frog olfactory receptor cells (Rana ridibunda) were isolated with an enzyme-free
      procedure and loaded with fura-2 from the patch pipette. The cells responded to
      superfusion with "IP3-odorants" with an inward current and an increase of the
      intracellular Ca2+ concentration. [Ca2+]i. An odorant-induced inward current and
      an increase in [Ca2+]i were also observed while flooding cells with 1 mM cAMP
      from the pipette, a condition which drives the cAMP signal pathway into
      adaptation. Flooding of cells with 50 microM IP3 from the pipette also induced an
      inward current with an increase in [Ca2+]i in normal Ringer solution and an
      inward current without changes in [Ca2+]i in Ca(2+)-free solution. The
      experiments suggest that IP3 activates a cation channel at the plasma membrane,
      allowing inflow of Na+ and Ca2+ ions.

PMID- 8753817
TI  - HIV encodes for its own CD4 T-cell superantigen mitogen.
AB  - Previously we reported that Nef protein from human immunodeficiency virus (HIV)
      induces proliferation of human peripheral blood mononuclear cells (PBMC). Herein,
      we show that HIV replicates in cells activated by Nef. PBMC proliferated in
      response to Nef and were capable of producing significant amounts of infectious
      virus upon infection. Polyclonal antibodies to Nef synthetic peptides blocked
      proliferation and neutralized infection. Characteristic of superantigens, T-cell
      proliferation in response to Nef required antigen-presenting cells and showed CD4
      Vb preferences as previously shown. These findings suggest that Nef is a virally
      encoded T-cell superantigen and, as such, may be vital in the establishment of
      HIV infection in a new host and in subsequent disease pathogenesis.

PMID- 8753818
TI  - Gene product identification and promoter analysis of hig locus of plasmid Rts1.
AB  - The hig (host inhibition of growth) genes of plasmid Rts1 belong to the plasmid
      encoded proteic killer gene family. Compared with other proteic killer genes
      described so far, hig is unique in that the toxic part (higB) exists upstream of
      the antidote gene (higA). Here we describe results of the promoter analysis of
      hig genes together with identification of the proteic gene products of higA and
      higB. Two promoters were identified in the hig locus; a stronger one, named Phig,
      is located upstream of higB and a weaker one, PhigA, is upstream of higA within
      the higB coding region. The Phig activity was negatively regulated by HigA and
      this regulation was augmented by HigB, whereas PhigA was not subjected to such a
      regulation.

PMID- 8753819
TI  - Hamster liver cytochrome P450 (CYP2A8) as a 4-hydroxylase for 2,5,2',5'
      tetrachlorobiphenyl.
AB  - Metabolism of 2,5,2',5'-tetrachlorobiphenyl (TCB) was studied using liver
      microsomes of hamsters and two hamster P450 isoforms, CYP1A2 and 2A8. CYP2A8
      catalyzed selectively 4-hydroxylation of 2,5,2',5-TCB at a rate of 21.7
      pmol/min/nmol P450. In contrast, CYP1A2 showed no activity for hydroxylation of
      2,5,2',5'-TCB. Immunological study revealed that rabbit antiserum against CYP2A8
      almost completely inhibited the microsomal 4-hydroxylation but that against
      CYP1A2 did not. It was also shown that the induction pattern of CYP2A8 protein by
      P450 inducer was similar to that of the 4-hydroxylase activity in hamster liver
      microsomes. These results suggest that CYP2A8 plays a major role in the 4
      hydroxylation of 2,5,2',5'-TCB in hamster liver.

PMID- 8753820
TI  - The fetal specific gene CYP3A7 is inducible by rifampicin in adult human
      hepatocytes in primary culture.
AB  - We investigated by RNase protection the differential expression of CYP3A4 and
      CYP3A7 mRNAs in fetal and adult human livers and in adult hepatocytes in primary
      culture. Our results show that CYP3A7 is expressed in the liver of 8 of 9 adult
      Caucasians examined, at an average level of 1.7% of the level found in a fetal
      liver. CYP3A4 mRNA appeared to be expressed in this fetal liver. In adult
      hepatocytes in primary culture, the constitutive level of CYP3A4 mRNA was low but
      detectable after 96 hours in untreated cells, but CYP3A7 mRNA remained
      undetectable. However, when the cells were treated for 48 hours with 25 microM
      rifampicin, both CYP3A4 and CYP3A7 mRNAs were strongly induced in the 3 and in 2
      of 3 cultures examined, respectively. Using an isoelectric focusing
      immunoblotting the two proteins were resolved. Protein CYP3A4 was detectable in
      induced cells but CYP3A7 was not. These results show for the first time that
      CYP3A7 and CYP3A4 mRNAs, but not the proteins, are co-inducible by rifampicin in
      adult human hepatocytes in culture.

PMID- 8753821
TI  - [40-year work anniversary of Prof. dra hab. med. Joseph Szczekot].

PMID- 8753822
TI  - [Analysis of clinical symptoms in shoulder arthropathy].
AB  - Frequency of chosen clinical symptoms has been analyzed in 236 patients aged 10
      to 80 years with shoulder pathology. It was found that "impingement syndrome" is
      characteristic for periarthritis humeroscapularis simplex. Active and passive
      movement restriction of the shoulder was frequently observed in periarthritis
      humeroscapularis simplex acuta; passive one greater than 50% was typical for
      capsulitis adhesiva. Crepitus at the movements, muscle wasting, impingement
      syndrome pain at the abduction and external rotation against resistance is
      indicative of periarthritis humeroscapularis destructive. Sonographic assessment
      of the shoulder is recommended in every case with the biceps long head rupture
      suspicion.

PMID- 8753823
TI  - [Studies of the degree of movement in the flexor pollicis longus tendon at the
      forearm with functioning pulleys in the thumb and after their excision].
AB  - The relative value of three pulleys in the thumb has been evaluated by serial
      resections and subsequent measurement of flexor pollicis longus tendon excursion
      at the level of the forearm. The metacarpophalangeal pulley appears to be the
      most important and should be preserved or reconstructed if normal tendon function
      is to result.

PMID- 8753824
TI  - [Contractures and growth disturbances in the hip and pelvis as the cause of
      "idiopathic scoliosis". Biomechanical considerations].
AB  - Author's own observations on etiology of "idiopathic scoliosis" in children and
      adolescents are presented. Abduction or flexion-abduction contracture of the hip,
      mainly right one, is the chief cause of "idiopathic scoliosis". Scoliosis is the
      final deformity in the chain of malformations commencing in newborns and infants,
      known as "contracture syndrome". This condition is described by many authors, Mau
      and Green-Griffin were the first ones. Adduction contracture of the left hip
      leads to secondary dysplasia of this joint. Coexisting abduction contracture of
      the right hip is usually neglected. Insufficient adduction in the right hip in
      extension causes functional elongation of the right extremity and oblique
      positioning of the pelvis, thus initiating left hand side lumbar, thoraco-lumbar
      or lumbo-sacral scoliosis. As the next step thoracic scoliosis develops. Early
      and late clinical and radiographic symptoms are presented, prophylactics and
      treatment is discussed.

PMID- 8753825
TI  - [Point of view].

PMID- 8753826
TI  - [Injuries of the spinal cord and vertebral column in children and adolescents].
AB  - A review of 127 pediatric patients admitted to the Department of Neurosurgery
      between 1965 and 1993 because of spinal cord and vertebral column injuries is
      presented. The aim of this paper is to relate clinical appearance and age of the
      patient. Patients were subdivided into two age groups on the grounds of skeletal
      development features. The first included 22 patients (3-14 years of age), the
      second one included 105 patients (15-18 years of age). Accident type, injury
      mechanism, level of the spinal injury and type of treatment differed in these
      groups as was found clinically and statistically. Younger group was mostly
      treated conservatively and the results of treatment were better.

PMID- 8753827
TI  - [Relationship between time of ossification center appearance and hip joint
      development stage using Graf's method].
AB  - The aim of this paper was to relate time of the ossification center appearance
      and development stage according to Graf. Retrospective analysis included 4546
      sonograms in children from 1 to 6 months of age and 1252 sonograms in 313 healthy
      newborns. An earlier appearance of the ossification center was found in females
      (7 weeks against 10 weeks of life in males). Statistically significant
      relationship was found between the delay in the ossification center appearance
      time and hip dysplasia. The delay exceeding 6 months is suggestive of serious
      pathology and complications in later stages of hip development.

PMID- 8753828
TI  - [Scintigraphy examination in differential diagnosis and evaluation during the
      course of Perthes disease].
AB  - Forty-four bone scintigraphies were done in 37 children with diagnosis or
      suspicion of Perthes disease. In 5 children with transient coxitis 3 hips were
      normal and 2 presented slightly increased uptake. In 13 cases of epiphyseal
      dysplasia 12 hips were normal; one presented decreased uptake. Nineteen Perthes
      cases showed typical uptake deficits; 3 joints showed slight increase of uptake,
      3 joints were normal. Scintigraphy was related to different stages of Perthes
      disease. The value of bone scintigraphy in Perthes differentiation and monitoring
      was discussed.

PMID- 8753829
TI  - [Use of densitometric examination in evaluation of cementless hip
      endoprosthesis].
AB  - Five patients underwent densitometry in order to establish bone mineral content
      (BMC) and bone mineral density (BMD) around Parhofer-Monch total hip components.
      The measurements were taken with LUNAR DPX unit twice: 11 days and 6 month
      postoperatively. "Orthopedic" software was employed to analyze them. Bone around
      the stem was evaluated with "auto analysis" option and relation to Gruen zones;
      "manual analysis" was used in modified DeLee and Charnley zones around the
      acetabulum. After six months BMC and BMD decrease in all Gruen zones was noted.
      In DeLee and Charnley zones BMC and BMD decreased in field 1 but slightly
      increased in field 2 and 3. The authors consider densitometry as important tool
      for monitoring and documentation of postoperative bone reaction to the implanted
      endoprosthesis.

PMID- 8753830
TI  - [Value of intraoperative diagnostic radiography in diagnosis of femoral head nail
      penetration].
AB  - Most of the complications of surgical treatment for slipped capital femoral
      epiphysis result from unrecognized joint penetration. Standard radiographic
      projections are unable to locate implants precisely since the tridimensional
      joint is viewed in one plane at a time. The use of a single screw placed in the
      center of the femoral head prevents unrecognized joint penetration.

PMID- 8753831
TI  - [Posterolateral rotatory knee joint instability. I. Anatomy of injuries and
      diagnosis].
AB  - Posterolateral rotatory knee joint instability is an uncommon but debilitating
      injury. Its pathomorphology as well as basic principles of clinical and
      instrument aided diagnosis are presented.

PMID- 8753832
TI  - [Atypical use of Zespol stabilizers in treatment of long bone shaft fractures].
AB  - Two cases of long bone shaft fracture at the border of previously implanted AO
      bone plate treated with Zespol fixator are presented. Good fixation was achieved
      with AO plate left in place and Zespol platform screws introduced in place of
      removed AO screws. These two methods can be combined in exceptional cases.

PMID- 8753833
TI  - [Soft tissue pathology complicating Zespol external fixation].
AB  - A series of 179 patients with lower externally fixed has been reviewed. In 14
      cases purulent exudation around Zespol implants occurred, in 37 cases non
      purulent infection was noted. Insufficient hygiene observation was identified as
      the chief cause. Management of these conditions is presented, 1 case of allergic
      reaction and 1 case of malignant neoplastic change are reported.

PMID- 8753835
TI  - [Prof. dr hab. med. Joseph Kozak. Obituary].

PMID- 8753836
TI  - The role of nitric oxide in the development of asthma.
AB  - This review describes the biosynthesis of nitrogen oxide, its relationship with
      asthmatic inflammation and its possible role in modulating immune response to
      inhaled allergens. Nitric oxide has been shown to have many actions from
      neurotransmission to memory. It is produced enzymatically by nitric oxide
      synthase which exists in several isoforms. The inducible form has been identified
      in endothelial cells, smooth muscle cells, epithelial cells, macrophages,
      fibroblasts, and neutrophils. Nitric oxide has been detected in the exhaled air
      of several animal species including humans, and increased levels are found in
      patients with inflammatory airways diseases such as asthma and bronchiectasis. As
      yet the cellular source of exhaled nitric oxide is uncertain. The precise effects
      of nitric oxide on the airways have yet to be completely determined, but is has
      been observed that nitric oxide has a selective suppressive effect on the Th1
      subset of helper T cells. This has led to the hypothesis that raised levels of
      nitric oxide may interfere with the balance between Th1 and Th2 cell types
      leading to a predominantly Th2 type response associated with allergic asthmatic
      symptoms. Whilst this simple inorganic gas has an important role to play in the
      aetiology of asthma, the true extent of this role has yet to be determined.

PMID- 8753837
TI  - The murine thymic microenvironment: changes with age.
AB  - Immunosenescence has been well described in both human and a variety of animal
      species and has an important influence on changes in immune function. Although
      several mechanisms may be operating to explain the alterations in immune function
      with age, one factor that has attracted significant attention has been the
      progressive age-dependent involution of the thymus. Hitherto, most studies of
      thymus have focused only on thymocytes. We have now taken advantage of a well
      defined panel of monoclonal antibodies (mAbs called MTS) that recognize and
      characterize the thymic miroenvironment, including epithelial and nonepithelial
      elements. Recent data using these MTS mAbs have disclosed significant
      abnormalities in the thymic cortex in models of murine lupus including the
      unusual appearance of medullary-type epithelial cells in the cortical areas and
      the presence of epithelial free spaces or 'cortical holes'. In this study, we
      investigated age-related changes in the thymic microenvironment in 12-month-old
      C3H/HeJ, C57BL/6 and BALB/c mice. Controls included thymus from young 4-to 6-week
      old mice as well as 6-month-old BALB/c mice. As expected, the thymus of all 12
      month-old mice manifested normal and distinctive separation of cortical and
      medullary epithelium. However, unlike younger mice, the 12-month-old mice had
      severe changes in these regions. For example, in older mice, the cortex and
      medulla were diffusely irregular and atrophic and had a poorly defined cortico
      medullary junction; the former having small disrupted epithelial networks, and
      the latter containing clusters of atrophic cells. Moreover, the extracellular
      matrix was increased and contained large irregularly shaped clusters.
      Interestingly, the thymus of 6-month-old mice expressed some changes within the
      medullary epithelium and the extracellular matrix, but the cortical epithelium
      remained unchanged. These age-related degenerative changes in the thymic
      microenvironment differ significantly from the abnormalities identified in
      autoimmunity and may be a factor in immunosenescence.

PMID- 8753838
TI  - Thalidomide and its metabolites have no effect on human lymphocyte proliferation.
AB  - Thalidomide is a drug that is being used in several diseases with an
      immunological component, but the effects on the different immune functions have
      only been studied partially. Therefore, we studied the effect of thalidomide on
      PPD-or Con-A-induced proliferation of human mononuclear cells. We found no direct
      effect of thalidomide at up to 50 micrograms/ml on the cultures. Cells taken from
      subjects 6 h after ingestion of 200 mg of thalidomide proliferated equally well
      to PPD and Con-A than cells taken prior to drug administration. Plasma taken from
      subjects that ingested 200 mg of thalidomide 6 h before did not affect the
      proliferative response of their own cells when added to the cultures. Plasma from
      rabbits that were injected with doses 5 or 15 times higher than the dose given to
      humans did not diminish the proliferative response of human mononuclear cells to
      PPD. We conclude that neither thalidomide nor its metabolites affect the
      proliferative response of human mononuclear cells.

PMID- 8753839
TI  - Pharmacologic study of basophil histamine release induced by monocyte chemotactic
      protein-1 with kinase inhibitors.
AB  - Monocyte chemotactic protein-1 (MCP-1)/monocyte chemotactic activating factor has
      a potent histamine-releasing activity for basophils and is a major component of
      IgE-independent histamine-releasing factors (HRF). In this study, we examined the
      effect of a panel of kinase inhibitors on MCP-1-induced histamine release from
      human basophils to characterize the signaling pathway used by this chemokine.
      Genistein (3 micrograms/ml), an inhibitor of tyrosine kinase, inhibited MCP-1
      induced histamine release by 44%. Wortmannin is a specific inhibitor of
      phosphatidylinositol 3 kinase (PI-3 kinase). It blocked MCP-1-induced histamine
      release with an IC50 of 3.3 x 10(-8) M indicating a role of PI-3 kinase in this
      reaction. KT5926, an inhibitor of myosin light chain kinase, also inhibited
      histamine release in response to MCP-1 with an IC50 of 10(-6) M. Staurosporine, a
      potent inhibitor of protein kinase C, although being not specific, augmented MCP
      1-induced histamine release by 31.9% at 10(-6) M. These results indicate the
      possible involvement of a series of kinases, including PI-3 kinase, in the signal
      transduction pathway used by MCP-1.

PMID- 8753841
TI  - Eosinophil peroxidase deficiency in New Zealand white mice.
AB  - Eosinophil peroxidase (EPO) is one of the granule enzymes in the eosinophil
      specific granules and is distinct from myeloperoxidase. Here we report that
      peroxidase activity was absent in eosinophils of New Zealand White (NZW) mice.
      When NZW, New Zealand Black and their F1 mice were treated with cyclophosphamide
      followed by Toxocara canis infection, the kinetic changes in the number of
      eosinophils in peripheral blood, determined by counting in Hinkelman's diluting
      fluid, were almost comparable among the three strains. However, when their blood
      films were stained for peroxidase reaction, eosinophils of NZW mice, but not of
      the other strains, lacked EPO activity, though their specific granules were
      stained by eosin Y. Sudan black staining for phospholipid was also negative in
      eosinophils of NZW mice. EPO deficiency in NZW eosinophils was further confirmed
      by electron-microscopic observations and by measuring EPO activity in the
      extracts of eosinophil-rich cell suspensions. These results indicate that NZW
      eosinophils share most of the features with human EPO-deficient eosinophils,
      suggesting that the NZW mouse is a murine counterpart of human EPO deficiency.

PMID- 8753840
TI  - Oxatomide inhibits the release of proinflammatory mediators from human basophils
      and mast cells.
AB  - Oxatomide (OXA), a histamine H1 receptor antagonist, is effective in the
      treatment of patients with allergic rhinitis, some allergic skin disorders, and
      bronchial asthma. We have characterized the effect of OXA on the immunologic
      release of preformed (histamine and tryptase) and de novo synthesized mediators
      (leukotriene C4:LTC4 and prostaglandin D2:PGD2) from human basophils and mast
      cells purified (from 10 to 82%) from human lung parenchyma (HLMC) and skin tissue
      (HSMC). Preincubation (15 min, 37 degrees C) of basophils with OXA (10(-7)-10(-5)
      M) before Der p I antigen or anti-IgE challenge concentration-dependently (10
      40%) inhibited the immunologic release of histamine and LTC4. OXA (10(-7)-10(-5)
      M) also inhibited (10-40%) histamine, tryptase and LTC4 release from HLMC
      activated by anti-IgE. In addition, OXA caused a concentration-dependent
      inhibition of histamine, tryptase and PGD2 release from HSMC immunologically
      challenged with a monoclonal antibody against the alpha chain of the high
      affinity receptor for IgE (anti-Fc epsilon RI) or anti-IgE. These results
      demonstrate that OXA exerts anti-inflammatory activities by inhibiting the
      release of preformed and de novo synthesized mediators from human basophils and
      mast cells.

PMID- 8753842
TI  - Alloxan diabetes reduces pleural mast cell numbers and the subsequent eosinophil
      influx induced by allergen in sensitized rats.
AB  - Alloxan damages insulin-producing cells and has been used as an inducer of
      experimental diabetes in several animal species. In this study, administration of
      alloxan (40 mg/kg, i.v.) to rats was followed by a selective and time-dependent
      reduction in the number of pleural mast cells (50 +/- 2.2%, p < 0.01; mean +/-
      SEM), while mononuclear cell and eosinophil counts were not altered. As compared
      to naive rats, the reduction in mast cell numbers was first noted 48 h following
      alloxan administration and remained unaltered for at least 60 days. It is
      noteworthy, that the depletion in the mast cell population was not accompanied by
      alterations in the total amount of histamine stored per cell. Sensitized rats
      turned diabetic by alloxan treatment performed 72 h before challenge showed a
      less pronounced antigen-induced mast cell degranulation compared to nondiabetic
      rats. Moreover, rats injected with alloxan 72 and 48 but not 24 h before
      challenge, reacted to allergenic challenge with 50% reduction in the number of
      eosinophils recruited to the pleural cavity within 24 h. We found that the less
      pronounced eosinophil accumulation did not relate to an intrinsic cell locomotor
      abnormality since eosinophils from diabetic rats presented similar chemotactic
      responses to LTB4 and PAF in vitro as compared to matching controls. Insulin (3
      IU/rat) restored basal levels of mast cells and reversed the subsequent
      inhibition of allergen-induced pleural eosinophilia, suggesting a causative
      relationship between these phenomena. Treatment with insulin also significantly
      increased the number of mast cells in the pleural cavity of naive rats (from 637
      +/- 57 to 978 +/- 79 x 10(3) cells/cavity, p < 0.001). Consistently, previous
      depletion of mast cells by means of local treatment with compound 48/80
      significantly reduced the antigen-induced eosinophil recruitment in sensitized
      animals. We conclude that the reduction in the pleural mast cell population noted
      in alloxan-treated rats could be directly implicated in the diminished pleural
      eosinophil influx following allergen challenge. This hyporesponsiveness is
      independent of an intrinsic abnormality of cell chemotaxis, but can be imitated
      by local mast cell depletion.

PMID- 8753843
TI  - Lack of association between atopy and the Ile181Leu variant of the beta-subunit
      of the high-affinity immunoglobulin E receptor.
AB  - A previous study has reported a strong association of a variant (Ile181Leu) of
      the beta-subunit of the high-affinity IgE receptor (Fc epsilon RI-beta) with
      allergic asthma bronchiale in a random patient sample. Based on their results the
      authors concluded that Fc epsilon RI-beta may be the maternally inherited, atopy
      causing locus. We have investigated 40 unrelated atopic patients, 30 with
      allergic asthma and 10 with atopic dermatitis or allergic rhinoconjunctivitis
      along with some of their relatives for the presence of Ile181Leu by nucleic acid
      sequence analysis and/or hybridization with mutation-specific oligonucleotide
      probes. None of the probands showed this mutation suggesting that its association
      with atopy may be restricted to certain populations or occur at lower frequency
      than reported.

PMID- 8753844
TI  - Shared IgE-binding sites among separated components of natural rubber latex.
AB  - BACKGROUND: IgE-mediated allergy to proteins present in natural rubber latex is a
      well-recognized problem. Latex contains a complex mixture of proteins ranging in
      molecular weight from 6 to > 200 kD. OBJECTIVE: The aim of this study was to
      determine whether shared allergenic sites exist on separate latex components.
      METHODS: Following electrophoresis, latex components at 14, 24, and 46 kD were
      electroeluted from SDS-polyacrylamide gels and used in ELISA inhibition and
      immunoblot inhibition studies of human latex-specific IgE antibodies. RESULTS: A
      minimum of 4 major allergenic sites (for convenience labeled A through D) were
      found to exist in 3 components of nonammoniated latex. Minimally, 2 are present
      in the 14-kD component (A, B) and 3 in the 24-kD component (A-C). The 46-kD
      fraction has 3 or more antigenic sites (A, C, D) but lacks one (B) that is
      present in both the 14- and 24-kD components. CONCLUSIONS: Four different IgE
      binding moieties were detected among three latex protein components (14, 24 and
      46 kD). Some of these allergenic sites were shared by two or more components.
      Recovery of these and others from fragmented latex components will allow
      identification of their amino acid composition and their availability will
      ultimately lead to better diagnostic and therapeutic options for patients with
      latex allergy.

PMID- 8753845
TI  - IgA and IgG binding components of wheat, rye, barley and oats recognized by
      immunoblotting analysis with sera from adult atopic dermatitis patients.
AB  - IgA and IgG antibody response of adult atopic dermatitis patients against
      neutral/ acidic fractions of wheat, rye, barley and oats was analyzed utilizing
      an immunoblotting method. Moreover, the antibody response against ethanol-soluble
      fraction of wheat was examined with serum pools of healthy donors, atopic
      dermatitis patients and patients with dermatitis herpetiformis or adult celiac
      disease. All patient sera revealed polymorphic IgA and IgG binding to cereal
      peptides with molecular weights of 11-97 kD. The antibody staining was
      essentially identical with atopic dermatitis patients and controls. Patients with
      dermatitis herpetiformis or celiac disease showed more intensive staining with
      the ethanol extract of wheat and showed more IgA-stained bands in immunoblotting.
      It seems that the presence of IgA and IgG antibodies to different cereal antigens
      is a result of natural exposure and in atopic dermatitis displays little
      diagnostic significance, in contrast to antigliadin antibody response in
      dermatitis herpetiformis and celiac disease.

PMID- 8753846
TI  - An approach to predictive testing of contact sensitizers in vitro by monitoring
      their influence on endocytotic mechanisms.
AB  - Endocytotic activation of epidermal Langerhans cells (LC) by immunogenic haptens
      is an early event during development of allergic contact dermatitis. In this work
      a fast and objective flow-cytometric assay for predictive in vitro testing of
      contact sensitizers by monitoring their influence on endocytotic mechanisms in
      murine LC was developed. Epidermal cell suspensions were labelled with a
      monoclonal antibody directed to MHC class II molecules and pH-sensitive
      fluorochrome-coupled second-step reagents. For untreated LC a significant
      quenching of fluorescence intensity by internalization of the MHC-antibody
      complexes into acidic compartments was noticed. Similar results were obtained in
      the presence of irritants, the lectin concanavalin A and the phorbol ester
      phorbol 12-myristate 13-acetate. In contrast stimulation with several well
      defined sensitizing compounds resulted in partial conservation of the
      fluorescence intensity due to the internalization of the labelled complexes into
      less acidic compartments. Monitoring this modulation of endocytosis is an
      effective in vitro method to test for properties typical for moderate and strong
      contact sensitizers. It will help to assess the risk of unknown chemicals to act
      as haptens and should be useful for restriction of animal experimentation in this
      field.

PMID- 8753847
TI  - Topical vitamin D3 downregulates IgE-mediated murine biphasic cutaneous
      reactions.
AB  - Hapten-specific and mast-cell-dependent biphasic (immediate and delayed-onset)
      cutaneous reactions were induced in a murine model by intravenous injection of
      anti-DNP IgE antibodies followed by a skin test. Four daily applications of
      topical 1 alpha,24(OH)2D3 ointment significantly inhibited both the immediate and
      the delayed-onset cutaneous reactions in a dose-dependent fashion, as well as the
      croton-oil-induced cutaneous reaction and DNFB contact sensitivity reaction. 1
      alpha,24(OH)2D3 itself did not show any sensitizing or irritant potential. The
      inhibitory effect of 1 alpha,24(OH)2D3 on these reactions was limited to the
      application site and no systemic effect was observed. Another vitamin D3 analog 1
      alpha,25(OH)2D3, also showed an inhibitory effect on IgE-mediated cutaneous
      reactions. These results suggest that topically applied 1 alpha,24(OH)2D3 might
      modulate IgE-mediated cutaneous reactions and could thus be useful in the
      treatment of certain human cutaneous disorders other than psoriasis and related
      keratinizing disorders.

PMID- 8753848
TI  - Culture and IgE synthesis of nasal B cells.
AB  - The interplay of inflammatory cells, mediators and cytokines during type I
      allergic reactions in the nose is well described. But even though allergen
      specific IgE is known to play a central role for the induction of these events,
      little is known about nasal B cells and their role in the local allergic
      reaction. It was the aim of the present study to examine the possibility to
      isolate and culture B cells from the nose. For this purpose allergic and
      nonallergic volunteers were challenged by nasal provocation with allergen. Cells
      were collected sequentially after nasal provocation by nasal lavage, B cells
      grown in the CD40 system and IgE production assessed by enzyme-linked filter spot
      assay and radioimmunoassay. IgE-producing B cells were detected after culture of
      nasal lavage cells in the CD40 system. Elevated levels of IgE were measured in
      culture supernatants from cells collected during the late-phase allergic
      reaction. We conclude that B cells can be isolated from the nose and may serve as
      an interesting source of B cells after in vivo contact with antigen.

PMID- 8753849
TI  - Interleukin 8 in bronchoalveolar lavage of asthmatic and chronic bronchitis
      patients.
AB  - Interleukin 8 (IL-8) is a chemoattractant cytokine having a distinct target
      specificity for the neutrophil. However, it was also found to be active on primed
      eosinophils. IL-8 was measured by enzyme immunoassay in the bronchoalveolar
      lavage fluid (BALF) of 9 control subjects, 19 asthmatics and 36 chronic
      bronchitis patients. Its levels were correlated with neutrophil and eosinophil
      counts as well as levels of myeloperoxidase (MPO) and eosinophil cationic protein
      in the BALF. Asthmatic and chronic bronchitis patients had elevated levels of IL
      8 in comparison with normal subjects. There was no correlation between the
      severity of asthma or chronic bronchitis and IL-8 levels. In asthmatic subjects
      there was a correlation between IL-8 and MPO levels (p < 0.0001, Spearman test).
      There was no significant correlation between eosinophils and IL-8. In chronic
      bronchitis there was a correlation between IL-8 and MPO levels as well as between
      IL-8 and neutrophil counts (p < 0.004 and p < 0.0152, respectively, Spearman
      test). IL-8 is involved in neutrophilic inflammation in asthma and chronic
      bronchitis, but differences in the IL-8 regulation of neutrophils were observed
      in both diseases.

PMID- 8753850
TI  - Oncogene expression in patients with familial polyposis coli/Gardner's syndrome.
AB  - We evaluated whether c-myc and ras P-21 oncogene expression could identify
      familial polyposis coli/Gardner's syndrome patients at risk for colon cancer.
      Monoclonal antibodies recognizing c-myc and ras P-21 proteins were used in
      immunohistochemistry to stain 26 paraffin-embedded tissue specimens collected
      over 12 years from 5 familial polyposis coli/Gardner's syndrome patients at
      various stages of their disease. Differences in staining intensity between
      specimens were noted with each of the two tissues markers; however, c-myc showed
      also a distinct cellular staining pattern in patients with advanced histologic
      features. The c-myc oncogene exhibited strong homogeneous cytoplasmic staining in
      all adenocarcinoma specimens; weak cytoplasmic staining was found in normal
      biopsies and in 5/10 familial polyposis coli/Gardner's syndrome specimens in the
      early stage of disease. In contrast, a heterogeneous staining pattern with a
      strong supranuclear and weak nuclear and cytoplasmic staining was demonstrated in
      specimens with advanced histologic features of familial polyposis coli/ Gardner's
      syndrome and also in postoperative ileal specimens. Anti-ras P-21 antibody, on
      the other hand, demonstrated a homogeneous cytoplasmic staining pattern in all
      specimens. We feel that the c-myc oncogene expression, in distinction to that of
      ras P-21, has potential as a genetic tissue marker to distinguish early from more
      progressive disease.

PMID- 8753851
TI  - Colorectal intussusception: an unusual gastrointestinal complication of
      hereditary angioedema.
AB  - A 21-year-old man with a history of hereditary angioedema presented with
      protracted abdominal pain which failed to respond to infusion of C1 inhibitor
      concentrate. Evaluation by CT scan revealed extensive colorectal intussusception
      requiring surgical intervention. Under replacement therapy with C1 inhibitor
      concentrate, both the operation under general anesthesia and the postoperative
      phase were uneventful. The intraoperative examination suggested initiation of
      intussusception by local mucosal edema in the transverse colon.

PMID- 8753852
TI  - Role of strong anchor residues in the effective binding of 10-mer and 11-mer
      peptides to HLA-A*2402 molecules.
AB  - The binding capacity of one-hundred-and-seventy-two 8-mer to 11-mer peptides
      carrying HLA-A24 anchor residues to HLA-A*2402 molecules was analyzed by using a
      HLA class I stabilization assay. Most (76. 2%) of these peptides bound to HLA
      A*2402 molecules. These results confirmed previous findings that Tyr and Phe at
      P2 as well as Phe, Trp, Ile, and Leu at the C-terminus were main anchor residues
      for HLA-A*2402. Tyr at P2 was a stronger anchor residue than Phe, while bulky
      aromatic hydrophobic residues Phe and Trp at the C-terminus are stronger anchors
      than aliphatic hydrophobic residues Ile and Leu. These results were also
      supported by an analysis using a panel of mutated 9-mer peptides at P2 and P9.
      Taken together, these results suggest that HLA-A*2402 molecules have deep B- and
      F-pockets because they favor peptides carrying bulky aromatic hydrophobic
      residues at P2 and the C-terminus. The affinity of 8-mer peptides was
      significantly lower than that of 9-mer to 11-mer peptides, while there was no
      difference in affinity between 9-mer, 10-mer, and 11-mer peptides. The affinity
      of peptides carrying bulky aromatic hydrophobic residues at the C-terminus was
      higher than that of peptides carrying aliphatic hydrophobic residues in each of
      the 8-mer to 11-mer peptides, though the greatest difference in affinity was
      observed in 11-mer peptides. The strong interaction of side chains of these
      anchor residues with the corresponding pockets may permit the effective binding
      of 10-mer and 11-mer peptides to HLA-A*2402 molecules.

PMID- 8753853
TI  - Association between the Rfp-Y haplotype and the incidence of Marek's disease in
      chickens.
AB  - Certain haplotypes at the major histocompatibility (B) complex (Mhc) of the
      chicken provide an easily demonstrated influence on tumor formation following
      infections with Marek's disease virus (MDV). Recognition that there is a second
      histocompatibility complex of genes in the chicken, Rfp-Y, comprised of Mhc class
      I and class II genes, some of which are at least transcribed, evokes the question
      of whether this gene complex might also influence the outcome of MDV infections.
      To test this hypothesis, pedigree-hatched chicks in families from the original
      Rfp-Y-defining stock in which three Rfp-Y and two B system haplotypes are
      segregating were challenged with the RB1B strain of MDV. Birds with the Y3/Y3
      genotype were found to have 2.3 times the risk of developing a tumor compared
      with birds with other Rfp-Y genotypes combined (P <0.02). Additionally, birds
      carrying the BR9/B11 genotype had 2.3 times the risk of tumor formation, relative
      to birds with the B11/B11 genotype (P <0.02). We found no evidence for an
      interaction between genotypes within the B and Rfp-Y systems. These data provide
      evidence that Rfp-Y haplotypes, as well as B haplotypes, can significantly
      influence the outcome of infection with MDV.

PMID- 8753854
TI  - Peptide binding characteristics of the coeliac disease-associated DQ(alpha1*0501,
      beta1*0201) molecule.
AB  - Genetic susceptibility to coeliac disease (CD) is strongly associated with the
      expression of the HLA-DQ2 (alpha1(*)0501, beta1(*)0201) allele. There is evidence
      that this DQ2 molecule plays a role in the pathogenesis of CD as a restriction
      element for gliadin-specific T cells in the gut. However, it remains largely
      unclear which fragments of gliadin can actually be presented by the disease
      associated DQ dimer. With a view to identifying possible CD-inducing antigens, we
      studied the peptide binding properties of DQ2. For this purpose, peptides bound
      to HLA-DQ2 were isolated and characterized. Dominant peptides were found to be
      derived from two self-proteins: in addition to several size-variants of the
      invariant chain (li)-derived CLIP peptide, a relatively large amount of an major
      histocompatibility complex (MHC) class I-derived peptide was found. Analogues of
      this naturally processed epitope (MHClalpha46 - 63) were tested in a cell-free
      peptide binding competition assay to investigate the requirements for binding to
      DQ2. First, a core sequence of 10 amino acids within the MHClalpha46 - 63 peptide
      was identified. By subsequent single amino acid substitution analysis of this
      core sequence, five putative anchor residues were identified at relative
      positions P1, P4, P6, P7, and P9. Replacement by the large, positively charged
      Lys at these positions resulted in a dramatic loss of binding. However, several
      other non-conservative substitutions had little or no discernable effect on the
      binding capacity of the peptides.

PMID- 8753855
TI  - Divergent intron arrangement in the MB1/LMP7 proteasome gene pair.
AB  - We sequenced the human MB1 gene from a cosmid clone mapping to chromosome 14q11.2
      12. The gene spans about 6 kilobases and contains three exons and two introns.
      There was no evidence of an alternative leader exon, which is a characteristic of
      the major histocompatibility complex (MHC)-encoded LMP7 gene, the closest
      relative of MB1, with which it shares 67% amino acid identity. Conceptual
      translation of the 5' end of the gene calls for a cleaved leader sequence of 59
      amino acids, consistent with western blot data. None of the MB1 gene's three
      exons were coincident with any of the six exons in LMP7. In contrast, in the
      delta-encoding gene and its counterpart, the MHC-encoded LMP2 gene (59% amino
      acid identity), all six exons are arranged at equivalent positions in respect to
      the coding frame. The unique structure of MB1 implies a separate origin or
      different selection pressures acting at this particular locus. DNA repeat
      analysis provides information on the minimum time of separation of the MB1/LMP7
      pair of genes.

PMID- 8753856
TI  - A new non-HLA multigene family associated with the PERB11 family within the MHC
      class I region.
AB  - In an effort to initiate steps designed to characterize the idiopathic
      hemochromatosis disease gene, the HLA-A/HLA-F region where this gene is in
      disequilibrium linkage with some polymorphic markers has been overlapped by a
      yeast artificial chromosome (YAC) contig. In order to achieve the physical
      mapping of these YACs and of the corresponding genomic region, we subcloned one
      of the YACs involved. A computer-assisted analysis of the sequence of one
      subclone led to the isolation of a potential exon that proved to belong to a new
      expressed messenger named HCGIX. After Southern blot analysis, the corresponding
      cDNA clone was found to belong to a new multigene family whose members are
      dispersed throughout the HLA class I region and are closely associated with
      members of another recently described multigene family designated PERB11. The
      data reported here suggest that these two multigene families form a cluster that
      have been dispersed together throughout the telomeric part of the major
      histocompatibility complex and have been involved in the genesis of this human
      class I region.

PMID- 8753857
TI  - Repression of the nonclassical MHC class I gene H2-M1 by cis-acting silencer DNA
      elements.
AB  - H2-M1 is a non-classical major histocompatibility complex (MHC) class I gene that
      is highly divergent from classical class I genes; M1 was the first gene in the
      recently classified M region of the mouse MHC to be cloned. Although the M1 DNA
      sequence contains normal splice sites, open reading frames within its exons, and
      a recognizable promoter, no M1 transcripts were detected in various healthy mouse
      tissues. However, M1 transcripts were detected in transfected L cells and in vivo
      in brains of M1 transgenic mice, albeit at very low levels, and the level of
      expression is correlated with transgene copy number. Analysis of the M1 promoter
      region identified a competent promoter capable of directing transcription, but
      whose expression is repressed by two strong upstream silencer elements, one
      mapping between -184 base pairs (bp) and -266 bp and the other between -1149 bp
      and -1702 bp. These studies suggest that M1 expression is highly regulated and
      restricted either temporally or to a very limited number of cell types.

PMID- 8753858
TI  - The structure, rearrangement, and ontogenic expression of DB and JB gene segments
      of the Mexican axolotl T-cell antigen receptor beta chain (TCRB).
AB  - We sequenced a total of 189 independent rearrangements in which the VB7.1 element
      is associated with CB1 (99 clones) or CB2 (90 clones) isotypes of the T-cell
      receptor (TCR) beta chain in the Mexican axolotl. Three stages of development
      were analyzed: 2.5 months, 10 months, and 25 months. Three JB1 segments were
      associated with the VB-CB1 rearrangements and six JB2 segments with VB-CB2. As in
      other vertebrates, some amino acid positions were conserved in all Jbetas (e. g.,
      Phe-108, Gly-109, Gly-111, Thr-112, and Val-116). Two 11 nucleotides DB-like
      sequences, differed by one (A or T) central residue and could be productively
      read in the three putative reading frames. Most of the DB1 and JB1 segments were
      in the VB-CB1 clones, and most of the DB2 and JB2 segments were in the VB-CB2
      clones, suggesting that the TCRB locus is organized into independent DB-JB-CB
      clusters that used the same collection of VB segments. About 40% of the beta
      chain VDJ junctions in 2.5-month-old larvae had N nucleotides, compared with
      about 73% in 10 - 25-month old animals. The beta-chain VDJ junctions had about
      30% of defective rearrangements at all stages of development, which could be due
      to the slow rate of cell division in the axolotl lymphoid organs, and the large
      genome in this urodele. Many of the axolotl CDRbeta3 sequences deduced for in
      frame VDJ rearrangements are the same in animals of different origins. Such
      redundancy could be a statistical effect due to the small number of thymocytes in
      the developing axolotl, rather than to some bias due to junctional preferences.

PMID- 8753859
TI  - Genomic structure, chromosome location, and alternative splicing of the human
      NKG2A gene.
AB  - A cosmid containing the human NKG2A gene was isolated. The gene was partially
      sequenced, revealing 7 exons, including one 5' untranslated exon. The 54 base
      pair exon 5 was missing in the published cDNA clone NKG2B, consistent with the
      existence of differential splicing. This was confirmed by reverse transcription
      polymerase chain reaction of total RNA from normal lymphocytes. The NKG2A gene
      was mapped by FISH to chromosome 12p12. 3-p13.1 in proximity to the CD69 and Prp
      genes. These data support the presence of a human lectin-like NK gene complex,
      analogous to the NK complex on mouse chromosome 6.

PMID- 8753860
TI  - Characteristics of initial and reinduced experimental autoimmune
      encephalomyelitis.
AB  - The factors which influence expression of autoimmune disease in the central
      nervous system are still poorly understood. We determined the characteristics of
      experimental autoimmune encephalomyelitis (EAE) in twelve different inbred
      strains of mice using either mouse spinal cord homogenate or synthetic peptides
      as the encephalitogen. We also determined whether these strains were susceptible
      to reinduction of EAE at six weeks after the initial injection. The incidence,
      time of onset, severity, duration, and number of spontaneous relapses varied
      widely among the different strains. Duration of initial EAE correlated
      significantly with incidence of spontaneous relapses, and was greatest in C57L
      mice and in mice with a C57BL/10 background. Most strains of mice recovered from
      initial EAE, but recovery was unusual in A.SW and PERA mice. Incidence of
      reinduced EAE differed from incidence of initial EAE in some strains and did not
      correlate with incidence of spontaneous relapse. We conclude that the same
      factors control disease duration and incidence of spontaneous relapse, and that
      these factors are independent of the factors which control initial incidence. The
      factors controlling incidence of reinduced EAE are distinct from those
      controlling spontaneous relapse, and may also differ from those controlling
      initial incidence. Further investigation of the mechanisms effecting recovery
      from EAE and the genetic background underlying those mechanisms may help us
      understand human diseases such as multiple sclerosis.

PMID- 8753861
TI  - Germline genomic structure of the B10.A mouse Tcra-V2 gene subfamily.
AB  - The number of mouse Tcra-V gene segments varies from one individual to another
      and is estimated to be about 100. Southern blot analysis revealed that most of
      the Tcra-V are organized in clusters composed of copies of Tcra-V belonging to
      different subfamilies. We analyzed in detail a Tcra-V subfamily and looked for
      new Tcra-V in order to improve the knowledge of the mouse Tcra locus
      organization. A series of genomic clones derived from the B10.A mouse strain
      enclosing these clusters was used to determined the structure of all the Tcra-V2.
      We were able to identify ten Tcra-V2. This study showed that the Tcra-V2 can be
      organized into three structural subgroups. The distribution of the genes along
      the Tcra locus, plus their structural organization, indicates that successive
      duplications occurred during the processes of expansion and contraction of the
      Tcra-V gene subfamilies. Several Tcra-V2 are also identical, indicating recent
      duplications. The most divergent Tcra-V2 differ by 7.4% nucleotides, leading to
      5.2% differences in amino acid contents.

PMID- 8753862
TI  - Expression of the interferon-gamma and interleukin-10 genes in rabbit HTLV-I
      transformed T-cell lines.

PMID- 8753863
TI  - Identification of C to T mutation at position -236 bp in the human NRAMP1 gene
      promoter.

PMID- 8753864
TI  - Chromosomal localization of the genes encoding rat CD4, CD8alpha, and CD8beta.

PMID- 8753865
TI  - Cloning, transfection, and DNA sequence of a second gene from the BoLA-A11
      haplotype.

PMID- 8753866
TI  - Nucleotide sequences of env and 3'LTROrf genes of endogenous mouse mammary tumor
      viruses encoding superantigen specific for TcrVbeta2.

PMID- 8753867
TI  - Regulation of neuromodulatory actions of angiotensin II in the brain neurons by
      the Ras-dependent mitogen-activated protein kinase pathway.
AB  - Angiotensin II (Ang II) stimulates norepinephrine transporter (NET) and tyrosine
      hydroxylase (TH) in the neurons, but the signal transduction mechanism of this
      neuromodulation is not understood. Treatment of neuronal cultures of hypothalamus
      brainstem with Ang II resulted in a time- and dose-dependent activation of Ras,
      Raf-1, and mitogen-activated protein kinase. This activation was mediated by the
      interaction of Ang II with the AT1, receptor subtype and was associated with the
      redistribution of AT1 receptor with Ras and Raf-1 on the neuronal membrane.
      Treatment with antisense oligonucleotide (AON) to mitogen-activated protein
      kinase decreased mitogen-activated protein kinase immunoreactivity by 70% and
      attenuated Ang II stimulation of c-fos, NET, and TH mRNA levels. This
      demonstrates that induction of these genes requires mitogen-activated protein
      kinase activation by Ang II. In contrast, AON to mitogen-activated protein kinase
      failed to inhibit Ang II stimulation of plasminogen activator inhibitor-1 mRNA
      levels. These results suggest that AT1 receptors are coupled to a Ras-Raf-1
      mitogen-activated protein kinase signal transduction pathway that is responsible
      for stimulation of NET and TH, two neuro-modulatory actions of Ang II in the
      brain.

PMID- 8753868
TI  - Regulation of dendritic spine density in cultured rat hippocampal neurons by
      steroid hormones.
AB  - The effects of gonadal steroid hormones on dendritic spines were studied in
      hippocampal neurons that were dissociated and grown in culture for 2-3 weeks.
      Exposure to estradiol caused up to a twofold increase in dendritic spine density
      in these neurons. The effect of estradiol was stereospecific and blocked by the
      steroid antagonist tamoxifen. The estradiol-induced rise in spine density was
      blocked by the NMDA antagonist APV, but not by the AMPA/KA antagonist DNQX. The
      estradiol-induced rise in spine density was blocked by the serine/threonine
      kinase inhibitor H7, but not by the tyrosine kinase inhibitor genestein, and was
      partially mimicked by PMA, an activator of protein kinase C. Estradiol also
      caused an increase in the fluorescence intensity of synaptophysin-immunoreactive
      terminals, corresponding to presynaptic boutons. Finally, estradiol caused a rise
      in [Ca]i reactivity of the cultured neurons to topical application of glutamate.
      These studies are the first to examine receptor and second messenger regulation
      of dendritic spines, and they illustrate the viability of cultured neurons as a
      powerful test system to address issues related to the regulation of dendritic
      spine maturation.

PMID- 8753869
TI  - Motor neurons are selectively vulnerable to AMPA/kainate receptor-mediated injury
      in vitro.
AB  - The nonphosphorylated neurofilament marker SMI-32 stains motor neurons in spinal
      cord slices and stains a subset of cultured spinal neurons ["large SMI-32(+)
      neurons"], which have a morphology consistent with motor neurons identified in
      vitro: large cell body, long axon, and extensive dendritic arborization. They are
      found preferentially in ventral spinal cord cultures, providing further evidence
      that large SMI-32(+) neurons are indeed motor neurons, and SMI-32 staining often
      colocalizes with established motor neuron markers (including acetylcholine,
      calcitonin gene-related peptide, and peripherin). Additionally, choline
      acetyltransferase activity (a frequently used index of the motor neuron
      population) and peripherin(+) neurons share with large SMI-32(+) neurons an
      unusual vulnerability to AMPA/kainate receptor-mediated injury. Kainate-induced
      loss of these motor neuron markers is Ca2+-dependent, which supports a critical
      role of Ca2+ ions in this injury. Raising extracellular Ca2+ exacerbates injury,
      whereas removal of extracellular Ca2+ is protective. A basis for this
      vulnerability is provided by the observation that most peripherin(+) neurons,
      like large SMI-32(+) neurons, are subject to kainate-stimulated Co2+ uptake, a
      histochemical stain that identifies neurons possessing Ca2+-permeable
      AMPA/kainate receptor-gated channels. Finally, of possibly greater relevance to
      the slow motor neuronal degeneration in diseases, both large SMI-32(+) neurons
      and peripherin(+) neurons are selectively damaged by prolonged (24 hr) low-level
      exposures to kainate (10 microM) or to the glutamate reuptake blocker L-trans
      pyrrolidine-2,4-dicarboxylic acid (100 microM). During these low-level kainate
      exposures, large SMI-32(+) neurons showed higher intracellular Ca2+
      concentrations than most spinal neurons, suggesting that Ca2+ ions are also
      important in this more slowly evolving injury.

PMID- 8753871
TI  - The role of K+ currents in frequency-dependent spike broadening in Aplysia R20
      neurons: a dynamic-clamp analysis.
AB  - The R20 neurons of Aplysia exhibit frequency-dependent spike broadening.
      Previously, we had used two-electrode voltage clamp to examine the mechanisms of
      this spike broadening (Ma and Koester, 1995). We identified three K+ currents
      that mediate action-potential repolarization: a transient A-type K+ current
      (I(Adepol)), a delayed rectifier current (IK-V), and a Ca(2+)-sensitive K+
      current(IK-CA). A major constraint in that study was the lack of completely
      selective blockers for I(Adepol) and I(K-V), resulting in an inability to assess
      directly the effects of their activation and inactivation on spike broadening. In
      the present study, the dynamic-clamp technique, which employs computer simulation
      to inject biologically realistic currents into a cell under current-clamp
      conditions (Sharp et al., 1993a,b), was used either to block I(Adepol) or I(K-V)
      or to modify their inactivation properties. The data in this paper, together with
      earlier results, lead to the following hypothesis for the mechanism of spike
      broadening in the R20 cells. As the spike train progresses, the primary
      responsibility for spike repolarization gradually shifts from I(Adepol) to I(K-V)
      to I(K-Ca). This sequence can be explained on the basis of the relative rates of
      activation and inactivation of each current with respect to the constantly
      changing spike durations, the cumulative inactivation of I(Adepol) and I(K-V),
      and the progressive potentiation of I(K-Ca). Positive feedback interactions
      between spike broadening and inactivation contribute to the cumulative
      inactivation of both I(Adepol) and I(K-V). The data also illustrate that when two
      or more currents have similar driving forces and partially overlapping activation
      characteristics, selectively blocking one current under current-clamp conditions
      can lead to a significant underestimate of its normal physiological importance.

PMID- 8753870
TI  - gp120-induced neurotoxicity in hippocampal pyramidal neuron cultures: protective
      action of TGF-beta1.
AB  - We found that TGF-beta1, a cytokine that previously has been reported to have
      neuroprotective effects, was able to prevent the toxicity induced by the HIV-1
      coat protein gp120 in hippocampal pyramidal neuron cultures. In the presence of
      glia, gp120 induced time- and dose-dependent cell death, which was more
      pronounced in mature (7-19 d in culture) than in young neurons (2-7 d in
      culture). Staining with nuclear dyes (propidium iodide and Hoechst 33342), in
      situ detection of DNA fragments, and DNA analysis on agarose gels indicated that
      apoptosis was mainly responsible for the death caused by the viral protein.
      However, after several days of treatment, death-displaying necrotic features also
      occurred. Neurotoxicity induced by gp120 was dependent on the activation of NMDA
      receptors and required the presence of glia as well as new protein synthesis.
      Thus, the effect of gp120 was abolished by the NMDA receptor antagonist APV and
      partially reduced by cycloheximide. Only modest neurotoxicity was observed in
      pure neuronal cultures deprived of the glia feeder layer. Fura-2-based
      videoimaging showed that treatment with gp120 enhanced the ability of NMDA to
      increase neuronal [Ca2+]i. The impairment of neuronal Ca2+ homeostasis was
      prevented completely by TGF-beta1. Therefore, it is likely that the
      neuroprotective action of the cytokine is attributable to its ability to
      stabilize neuronal [Ca2+]i.

PMID- 8753873
TI  - Cholinergic-dependent plateau potential in hippocampal CA1 pyramidal neurons.
AB  - Cholinergic stimulation of the hippocampal formation results in excitation and/or
      seizure. We report here, using whole-cell patch-clamp techniques in the
      hippocampal slice (34-35 degrees C), a cholinergic-dependent slow
      afterdepolarization (sADP) and long-lasting plateau potential (PP). In the
      presence of 20 microM carbachol, action potential firing evoked by weak
      intracellular current injection elicited an sADP that lasted several seconds.
      Increased spike firing evoked by stronger depolarizing stimuli resulted in long
      duration PPs maintained close to -20 mV. Removal of either Na+ or Ca2+ from the
      external media, intracellular Ca2+ ([Ca2+]i) chelation with 10 mM bis(2
      aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid, or the addition of 100 microM
      Cd2+ to the perfusate abolished both the sADP and PP. The sADP was depressed and
      the PP was abolished by either 10 microM nimodipine or 1 microM omega-conotoxin,
      whereas 1.2 microM tetrodotoxin was ineffective. The involvement of a Na+/Ca2+
      exchanger was minimal because both the sADP and PP persisted after equimolar
      substitution of 50 mM Li+ for Na+ in the external media or reduction of the bath
      temperature to 25 degrees C. Finally in the absence of carbachol the sADP and PP
      could not be evoked when K+ channels were suppressed, suggesting that depression
      of K+ conductances alone was not sufficient to unmask the conductance. Based on
      these data, we propose that a Ca2+-activated nonselective cation conductance was
      directly enhanced by muscarinic stimulation. The sADP, therefore, represents
      activation of this conductance by residual [Ca2+]i, whereas the PP represents a
      novel regenerative event involving the interplay between high-voltage-activated
      Ca2+ channels and the Ca2+-activated nonselective cation conductance. This latter
      mechanism may contribute significantly to ictal depolarizations observed during
      cholinergic-induced seizures.

PMID- 8753872
TI  - Multiple protein factors interact with the cis-regulatory elements of the
      proximal promoter in a cell-specific manner and regulate transcription of the
      dopamine beta-hydroxylase gene.
AB  - The dopamine beta-hydroxylase (DBH) gene is expressed selectively in
      noradrenergic and adrenergic neurons and neuroendocrine cells in the nervous
      system. A cAMP response element (CRE) residing at -181 to -174 bp from the
      transcription start site of the human DBH gene seems to be essential for DBH
      transcription. Potential cis-regulatory motifs such as AP1 and YY1 occur proximal
      to and overlap this CRE, endowing the area with a composite promoter structure.
      Using the DBH-expressing human neuroblastoma SK-N-BE(2)C and DBH-negative HeLa
      cell lines as model systems, we report here that this CRE/YY1/AP1 area interacts
      with multiple nuclear proteins, including CRE-binding protein (CREB) and
      transcription factor YY1 in a cell-specific manner. In support of the notion that
      multiple proteins bind to the CRE/YY1/AP1 area, DNase I foot-printing analysis
      has demonstrated that nuclear extracts protect an extended region (from -186 to 
      150 bp) relative to that protected by the purified CREB (from -186 to -171 bp).
      Site-directed mutational analysis has revealed differential roles of potential
      cis-regulatory motifs in regulation of DBH transcription. Strikingly, the YY1
      element positively regulated basal DBH transcription while simultaneously
      regulating cAMP-mediated induction negatively, which is a novel mechanism of
      promoter function. Furthermore, three additional DNA-binding sites have been
      identified by DNase I footprint analysis in the upstream 260 bp promotor region
      of the human DBH gene, of which two sites are cell-specific. These results
      support a model whereby multiple proteins bind to the 5'-proximal area in a cell
      specific manner and coordinately regulate the cell type-specific transcriptional
      activation of the DBH gene.

PMID- 8753874
TI  - Kinetics of NMDA channel opening.
AB  - The period required for NMDA channels to open for the first time after agonist
      binding (the first latency) was estimated in outside-out patch recordings from
      rat hippocampal neurons using fast-application techniques and the open channel
      blocker MK-801. In the presence of MK-801, brief applications of L-glutamate or
      the low-affinity agonist L-cysteate resulted in a similar amount of block despite
      the much shorter period of channel activation by L-cysteate. A brief
      coapplication of L-glutamate and MK-801 resulted in a block similar to that found
      with an application of L-glutamate in a background of MK-801. These results,
      along with our findings that MK-801 does not block desensitized receptors,
      indicate that NMDA channels have a mean first latency of approximately 10 msec,
      consistent with a peak open probability near 0.3. If NMDA channels at synapses
      behave similarly, relatively few channels would be required to produce the
      postsynaptic calcium transient associated with synaptic plasticity and
      developmental regulation.

PMID- 8753875
TI  - Ultrastructural localization of the vesicular monoamine transporter-2 in midbrain
      dopaminergic neurons: potential sites for somatodendritic storage and release of
      dopamine.
AB  - Midbrain dopaminergic neurons are known to release dopamine from somata and/or
      dendrites located in the substantia nigra (SN) and the ventral tegmental area
      (VTA). There is considerable controversy, however, about the subcellular sites
      for somatodendritic dopamine storage in these regions. In the present study, we
      used dual-labeling electron microscopic immunocytochemistry to localize the
      vesicular monoamine transporter-2 (VMAT2), a novel marker for sites of
      intracellular monoamine storage, within identified dopaminergic (tyrosine
      hydroxylase-containing) neurons in the rat SN and VTA. In dopaminergic perikarya,
      immunogold labeling for VMAT2 was localized to the Golgi apparatus,
      tubulovesicles that resembled smooth endoplasmic reticulum (SER), and the
      limiting membranes of multivesicular bodies. In dopaminergic dendrites, VMAT2 was
      extensively localized to tubulovesicles that resembled saccules of SER, and less
      frequently localized to isolated small synaptic vesicles (SSVs) or large dense
      core vesicles (DCVs). In rare cases, VMAT2-immunoreactive SSVs were clustered
      within the cytoplasm of an SN or a VTA dendrite. Dopaminergic dendrites in the
      VTA contained a significantly higher number of immunogold particles for VMAT2 per
      unit than those in the SN. Together, these observations support the proposal that
      dopamine is stored in and may be released from dendritic SSVs and DCVs, but
      suggest that the SER is the major site of dopamine storage within midbrain
      dopaminergic neurons. In addition, they provide new evidence that dopaminergic
      dendrites in the VTA may have greater potential for reserpine-sensitive storage
      and release of dopamine than those in the SN.

PMID- 8753876
TI  - Increased expression of IL-1beta converting enzyme in hippocampus after ischemia:
      selective localization in microglia.
AB  - Although the interleukin-1beta converting enzyme (ICE)/CED-3 family of proteases
      has been implicated recently in neuronal cell death in vitro and in ovo, the role
      of specific genes belonging to this family in cell death in the nervous system
      remains unknown. To address this question, we examined the in vivo expression of
      one of these genes, Ice, after global forebrain ischemia in gerbils. Using RT-PCR
      and Western immunoblot techniques, we detected an increase in the mRNA and
      protein expression of ICE in hippocampus during a period of 4 d after ischemia.
      Chromatin condensation was observed in CA1 neurons within 2 d after ischemia.
      Internucleosomal DNA fragmentation and apoptotic bodies were observed between 3
      and 4 d after ischemia, a period during which CA1 neuronal death is maximal. In
      nonischemic brains, ICE-like immunoreactivity was relatively low in CA1 pyramidal
      neurons but high in scattered hippocampal interneurons. After ischemia, ICE-like
      immunoreactivity was not altered in these neurons. ICE-like immunoreactivity,
      however, was observed in microglial cells in the regions adjacent to the CA1
      layer as early as 2 d after ischemic insult. The increase in ICE-like
      immunoreactivity was robust at 4 d after ischemia, a period that correlates with
      the DNA fragmentation observed in hippocampal homogenates of ischemic brains.
      These results provide the first evidence for the localization and induction of
      ICE expression in vivo after ischemia and suggest an indirect role for ICE in
      ischemic damage through mediation of an inflammatory response.

PMID- 8753877
TI  - Multiple subtypes of voltage-gated calcium channel mediate transmitter release
      from parasympathetic neurons in the mouse bladder.
AB  - Multiple subtypes of voltage-gated calcium channels are coupled to transmitter
      release from central neurons; however, only N-type channels have been shown to
      play a role in autonomic neurons. The aim of the present study was to investigate
      potential roles for other channel subtypes in transmitter release from
      parasympathetic neurons in the mouse bladder using calcium channel toxins alone
      and in combination. Transmitter release was measured indirectly by recording the
      contraction of bladder dome strips in response to electrical stimulation of the
      neurons by single pulses or trains of 20 pulses at 1-50 Hz. omega-Conotoxin-GVIA
      (GVIA) and omega-conotoxin-MVIIC (MVIIC) inhibited contractions in a
      concentration-dependent manner, with IC50 values of approximately 30 and 200 nM,
      respectively, at low stimulation frequencies. omega-Agatoxin-IVA (agatoxin) alone
      did not have any significant effect up to 300 nM. Cumulative addition of the
      toxins demonstrated that 300 nM agatoxin had a significant effect after N-type
      channels were blocked with 100 nM GVIA. MVIIC (3 microM) reduced the contraction
      amplitude further. Testing the toxins on the cholinergic or purinergic component
      of the contraction separately showed that acetylcholine release depends primarily
      on N-type channels and, to a lesser extent, on P- and Q-type channels, whereas
      ATP release involves predominantly P- and Q-type channels. In conclusion,
      parasympathetic neurons in the mouse bladder, like central neurons, use multiple
      calcium channel subtypes. Furthermore, the release of the two main transmitters
      in these neurons has differing dependencies on the calcium channel subtypes.

PMID- 8753878
TI  - Ultrastructural immunocytochemical localization of mu-opioid receptors in rat
      nucleus accumbens: extrasynaptic plasmalemmal distribution and association with
      Leu5-enkephalin.
AB  - mu-Opioid receptors and their endogenous ligands, including Leu5-enkephalin (LE),
      are distributed abundantly in the nucleus accumbens (NAC), a region implicated in
      mechanisms of opiate reinforcement. We used immunoperoxidase and/or immunogold
      silver methods to define ultrastructural sites for functions ascribed to mu
      opioid receptors and potential sites for activation by LE in the NAC. An
      antipeptide antibody raised against an 18 amino acid sequence of the cloned mu
      opioid receptor (MOR) C terminus showed that MOR-like immunoreactivity (MOR-LI)
      was localized predominantly to extrasynaptic sites along neuronal plasma
      membranes. The majority of neuronal profiles containing MOR-LI were dendrites and
      dendritic spines. The dendritic plasma membranes immunolabeled for MOR were near
      sites of synaptic input from LE-labeled terminals and other unlabeled terminals
      forming either inhibitory or excitatory type synapses. Unmyelinated axons and
      axon terminals were also intensely but less frequently immunoreactive for MOR.
      Observed sites for potential axonal associations with LE included coexistence of
      MOR and LE within the same terminal, as well as close appositions between
      differentially labeled axons. Astrocytic processes rarely contained detectable
      MOR-LI, but also were sometimes observed in apposition to LE-labeled terminals.
      We conclude that in the rat NAC, MOR is localized prominently to extrasynaptic
      neuronal and more rarely to glial plasma membranes that are readily accessible to
      released LE and possibly other opioid peptides and opiate drugs. The close
      affiliation of MOR with spines receiving excitatory synapses and dendrites
      receiving inhibitory synapses provides the first direct morphological evidence
      that MOR selectively modulates postsynaptic responses to cortical and other
      afferents.

PMID- 8753879
TI  - TGF-beta-induced apoptosis of cerebellar granule neurons is prevented by
      depolarization.
AB  - The regulation of programmed cell death in the developing nervous system involves
      target-derived survival factors, afferent synaptic activity, and hormone- and
      cytokine-dependent signaling. Cultured immature cerebellar granule neurons die by
      apoptosis within several days in vitro unless maintained in depolarizing (high)
      concentrations of potassium (25 mM K+). Here we report that transforming growth
      factors (TGF)-beta1, -beta2, and -beta3 accelerate apoptosis of these neurons
      when maintained in physiological (low) K+ medium (5mM K+) as assessed by measures
      of viability, quantitative DNA fragmentation, and nuclear morphology. TGF-beta
      induced apoptosis of these neurons is not blocked by CNTF and LIF, cytokines that
      enhance neuronal survival when applied alone, or by IGF-I, which prevents
      apoptosis upon potassium withdrawal. In contrast, neurons that differentiate in
      high K+ medium for several days in vitro acquire resistance to TGF-beta-mediated
      cell death. Granule neurons maintained in either low or high K+ medium produce
      latent, but not bioactive, TGF-beta1 and -beta2. Because neutralizing TGF-beta
      antibodies fail to augment survival of low K+ neurons, the cerebellar neurons are
      apparently unable to activate latent TGF-beta. Thus, apoptosis of low K+ neurons
      is not attributable to endogenous production of TGF-beta. Taken together, our
      data suggest that TGF-beta may limit the expansion of postmitotic neuronal
      precursor populations by promoting their apoptosis but may support survival of
      those neurons that have maturated, differentiated, and established supportive
      synaptic connectivity.

PMID- 8753880
TI  - Protection of retinal ganglion cells from natural and axotomy-induced cell death
      in neonatal transgenic mice overexpressing bcl-2.
AB  - Approximately half of the retinal ganglion cells (RGCs) present in the rodent
      retina at birth normally die during early development. Overexpression of the
      photo-oncogene bcl-2 recently has been shown to rescue some neuronal populations
      from natural cell death and from degeneration induced by axotomy of nerves within
      the peripheral nervous system. Here we study in vivo the role of the
      overexpression of bcl-2 in the natural cell death of RGCs and in the degenerative
      process induced in these cells by transection of the optic nerve. We find that in
      newborn bcl-2 transgenic mice, the number of RGCs undergoing natural cell death
      is considerably lower than in wild-type pups. Consistently, a vast majority (90%)
      of the ganglion cells found in the retina of neonatal transgenics are maintained
      in adulthood, whereas only 40% survive in wild-type mice. After transection of
      the optic nerve, the number of degenerating ganglion cells, determined by
      counting pyknotic nuclei or nuclei with fragmented DNA, is substantially reduced
      in transgenic mice. In wild-type animals, almost 50% of ganglion cells degenerate
      in the 24 hr after the lesion, whereas almost the entire ganglion cell population
      survives axotomy in transgenic mice. Therefore, overexpression of bcl-2 is
      effective in preventing degeneration of this neuronal population, raising the
      possibility that ganglion cells are dependent on the endogenous expression of bcl
      2 for survival. The remarkable rescue capacity of bcl-2 overexpression in these
      neurons makes it an interesting model for studying natural cell death and
      responses to injury in the CNS.

PMID- 8753881
TI  - Dual action of a carbohydrate epitope on afferent and efferent axons in cortical
      development.
AB  - During development of the mammalian cerebral cortex, ingrowing afferents from the
      thalamus take a path that is different from that of axons leaving the cortical
      plate. Thalamic axons arrive at the cortex at the time before their target cells
      of layer 4 are generated in the ventricular zone, but they invade the cortex only
      shortly before these cells have migrated to their final position in the cortex.
      Growth-promoting molecules are up-regulated in the developing cortical plate
      during this period. To identify such molecules, we have generated monoclonal
      antibodies against membrane preparations from rat postnatal cortex. In Western
      blots, one antibody (mAb 10) recognized a carbohydrate epitope of a glycoprotein
      with an apparent molecular weight extending from 180 to 370 kDa.
      Immunohistochemical staining revealed that the staining pattern of mAb 10 at
      embryonic stages delineates the pathway of thalamocortical axons, with only very
      faint labeling of the corticofugal pathway. In vitro assays in combination with
      time-lapse imaging indicated that mAb 10 has opposite effects on the growth of
      thalamic and cortical axons. The growth speed and axonal elongation of thalamic
      fibers on postnatal cortical membranes preincubated with mAb 10 was reduced
      compared with untreated cortical membranes. In contrast, cortical axons grew
      faster and stopped their growth less frequently after addition of mAb 10 to a
      cortical membrane substrate. Taken together, these results suggest that a
      carbohydrate moiety of a membrane-associated glycoprotein plays a role in the
      segregation of afferent and efferent cortical axons in the white matter.
      Moreover, the epitope recognized by mAb 10 might also contribute to regulation of
      the timing of the thalamocortical innervation at later developmental stages.

PMID- 8753882
TI  - Linear systems analysis of functional magnetic resonance imaging in human V1.
AB  - The linear transform model of functional magnetic resonance imaging (fMRI)
      hypothesizes that fMRI responses are proportional to local average neural
      activity averaged over a period of time. This work reports results from three
      empirical tests that support this hypothesis. First, fMRI responses in human
      primary visual cortex (V1) depend separably on stimulus timing and stimulus
      contrast. Second, responses to long-duration stimuli can be predicted from
      responses to shorter duration stimuli. Third, the noise in the fMRI data is
      independent of stimulus contrast and temporal period. Although these tests can
      not prove the correctness of the linear transform model, they might have been
      used to reject the model. Because the linear transform model is consistent with
      our data, we proceeded to estimate the temporal fMRI impulse-response function
      and the underlying (presumably neural) contrast-response function of human V1.

PMID- 8753883
TI  - Mnemonic responses of single units recorded from monkey inferotemporal cortex,
      accessed via transcommissural versus direct pathways: a dissociation between unit
      activity and behavior.
AB  - Three macaques were trained on a task in which a sequence of single visual images
      was presented serially, and the monkeys signaled whether the image was a new or a
      repeated one. The optic chiasm and splenium of the corpus callosum were
      transected, leaving the anterior commissure as the only path for cortical
      interhemispheric transfer. Images were presented to only one eye at a time. Re
      presentations of images to the same eye were recognized correctly in >95% of
      trials. A robust stimulus-specific adaptation (i.e., a reduced response to a
      repeated image) was seen in the population of single units recorded from
      inferotemporal cortex during these same trials. When an interhemispheric transfer
      was demanded of the animals (i.e., the re-presentation was made to the other
      eye), recognition performance was somewhat reduced, to 86% correct.
      Interestingly, in this situation the stimulus-specific adaptation disappeared
      completely. The disappearance occurred regardless of whether the transfer
      direction was from the hemisphere ipsilateral to the recording site to the
      hemisphere contralateral to the recording site, or vice versa. Thus, stimulus
      specific adaptation in inferotemporal cortex units is not required for
      recognition.

PMID- 8753885
TI  - Stimulus specificity of phase-locked and non-phase-locked 40 Hz visual responses
      in human.
AB  - Considerable interest has been raised by non-phase-locked episodes of
      synchronization in the gamma-band (30-60 Hz). One of their putative roles in the
      visual modality is feature-binding. We tested the stimulus specificity of high
      frequency oscillations in humans using three types of visual stimuli: two
      coherent stimuli (a Kanizsa and a real triangle) and a noncoherent stimulus ("no
      triangle stimulus"). The task of the subject was to count the occurrences of a
      curved illusory triangle. A time-frequency analysis of single-trial EEG data
      recorded from eight human subjects was performed to characterize phase-locked as
      well as non-phase-locked high-frequency activities. We found in early phase
      locked 40 Hz component, maximal at electrodes Cz-C4, which does not vary with
      stimulation type. We describe a second 40 Hz component, appearing around 280
      msec, that is not phase-locked to stimulus onset. This component is stronger in
      response to a coherent triangle, whether real or illusory: it could reflect,
      therefore, a mechanism of feature binding based on high-frequency
      synchronization. Because both the illusory and the real triangle are more target
      like, it could also correspond to an oscillatory mechanism for testing the match
      between stimulus and target. At the same latencies, the low-frequency evoked
      response components phase-locked to stimulus onset behave differently, suggesting
      that low- and high-frequency activities have different functional roles.

PMID- 8753884
TI  - Amphetamine and dopamine-induced immediate early gene expression in striatal
      neurons depends on postsynaptic NMDA receptors and calcium.
AB  - Amphetamine and cocaine induce the expression of both immediate early genes
      (IEGs) and neuropeptide genes in rat striatum. Despite the demonstrated
      dependence of these effects on D1 dopamine receptors, which activate the cyclic
      AMP pathway, there are several reports that amphetamine and cocaine-induced IEG
      expression can be inhibited in striatum in vivo by NMDA receptor antagonists. We
      find that in vivo, the NMDA receptor antagonist MK-801 inhibits amphetamine
      induction of c-fos acutely and also prevents downregulation of IEG expression
      with chronic amphetamine administration. Such observations raise the question of
      whether dopamine/glutamate interactions occur at the level of corticostriatal and
      mesostriatal circuitry or within striatal neurons. Therefore, we studied
      dissociated striatal cultures in which midbrain and cortical presynaptic inputs
      are removed. In these cultures, we find that dopamine- or forskolin-mediated IEG
      induction requires Ca2+ entry via NMDA receptors but not via L-type Ca2+
      channels. Moreover, blockade of NMDA receptors diminishes the ability of dopamine
      to induce phosphorylation of the cyclic AMP responsive element binding protein
      CREB. Although these results do not rule out a role for circuit-level
      dopamine/glutamate interactions, they demonstrate a requirement at the cellular
      level for interactions between the cyclic AMP and NMDA receptor pathways in
      dopamine-regulated gene expression in striatal neurons.

PMID- 8753886
TI  - Kainic acid-induced seizures enhance dentate gyrus inhibition by downregulation
      of GABA(B) receptors.
AB  - Seizures cause a persistent enhancement in dentate synaptic inhibition concurrent
      with, and possibly compensatory for, seizure-induced hippocampal
      hyperexcitability. To study this phenomenon, we evoked status epilepticus in rats
      with systemic kainic acid (KA), and 2 weeks later assessed granule cell
      inhibition with paired-pulse stimulation of the perforant path (PP) in vitro.
      Controls demonstrated three components of paired-pulse inhibition: early
      inhibition (10-30 msec), intermediate facilitation (30-120 msec), and late
      inhibition (120 msec to 120 sec). After seizures, inhibition in all components
      was enhanced significantly. The GABA(A) antagonist bicuculline blocked only early
      enhanced inhibition, demonstrating that both GABA(A) and GABA(B) postsynaptic
      receptors contribute to seizure-induced enhanced inhibition. In controls, the
      GABA(B) antagonist CGP 35348 increased both GABA(A) and GABA(B) responses in
      granule cells, suggesting that CGP 35348 acts presynaptically, blocking receptors
      that suppress GABA release. In contrast, slices from KA-treated rats were
      markedly less sensitive to CGP 35348. To test the hypothesis that GABA(B)
      receptors regulating GABA release are downregulated after seizures, we measured
      paired-pulse suppression of recurrent IPSPs, or disinhibition, using mossy fiber
      stimuli. Early disinhibition (< 200 msec) was reduced after seizures, whereas
      late disinhibition remained intact. CGP 35348 blocked the early component of
      disinhibition in controls and, to a lesser extent, reduced disinhibition in KA
      slices. However, paired monosynaptic IPSPs recorded intracellularly showed no
      difference in disinhibition between groups. Our findings indicate that seizure
      induced enhancement in dentate inhibition is caused, at least in part, by reduced
      GABA(B) function in the polysynaptic recurrent inhibitory circuit, resulting in
      reduced disinhibition and heightened GABA release.

PMID- 8753887
TI  - Three-dimensional statistical analysis of sulcal variability in the human brain.
AB  - Morphometric variance of the human brain is qualitatively observable in surface
      features of the cortex. Statistical analysis of sulcal geometry will facilitate
      multisubject atlasing, neurosurgical studies, and multimodality brain mapping
      applications. This investigation describes the variability in location and
      geometry of five sulci surveyed in each hemisphere of six postmortem human brains
      placed within the Talairach stereotaxic grid. The sulci were modeled as complex
      internal surfaces in the brain. Heterogeneous profiles of three-dimensional (3D)
      variation were quantified locally within individual sulci. Whole human heads,
      sectioned at 50 micrometer, were digitally photographed and high-resolution 3D
      data volumes were reconstructed. The parieto-occipital sulcus, the anterior and
      posterior rami of the calcarine sulcus, the cingulate and marginal sulci, and the
      supracallosal sulcus were delineated manually on sagittally resampled sections.
      Sulcal outlines were reparameterized for surface comparisons. Statistics of 3D
      variation for arbitrary points on each surface were calculated locally from the
      standardized individual data. Additional measures of surface area, extent in
      three dimensions, surface curvature, and fractal dimension were used to
      characterize variations in sulcal geometry. Paralimbic sulci exhibited a greater
      degree of anterior-posterior variability than vertical variability. Occipital
      sulci displayed the reverse trend. Both trends were consistent with developmental
      growth patterns. Points on the occipital sulci displayed a profile of variability
      highly correlated with their 3D distance from the posterior commissure. Surface
      curvature was greater for the arched paralimbic sulci than for those bounding
      occipital gyri in each hemisphere. On the other hand, fractal dimension measures
      were remarkably similar for all sulci examined, and no significant hemispheric
      asymmetries were found for any of the selected spatial and geometric parameters.
      Implications of cortical morphometric variability for multisubject comparisons
      and brain mapping applications are discussed.

PMID- 8753888
TI  - Cerebral representation of one's own past: neural networks involved in
      autobiographical memory.
AB  - We studied the functional anatomy of affect-laden autobiographical memory in
      normal volunteers. Using H2 15O positron emission tomography (PET), we measured
      changes in relative regional cerebral blood flow (rCBF). Four rCBF measurements
      were obtained during three conditions: REST, i.e.,, subjects lay at rest (for
      control); IMPERSONAL, i.e., subjects listened to sentences containing episodic
      information taken from an autobiography of a person they did not know, but which
      had been presented to them before PET scanning (nonautobiographical episodic
      memory ecphory); and PERSONAL, i.e., subjects listened to sentences containing
      information taken from their own past (autobiographical episodic memory ecphory).
      Comparing IMPERSONAL with REST (nonautobiographical episodic memory ecphory)
      resulted in relative rCBF increases symmetrically in both temporal lobes
      including the temporal poles and medial and superior temporal gyri. The same
      loci, however, with a stronger lateralization to the right hemisphere were
      activated in the comparison PERSONAL to REST (autobiographical episodic memory
      ecphory). In addition, the right temporomesial, right dorsal prefrontal, right
      posterior cingulate areas, and the left cerebellum were activated. A comparison
      of PERSONAL and IMPERSONAL (autobiographical vs nonautobiographical episodic
      memory ecphory) demonstrated a preponderantly right hemispheric activation
      including primarily right temporomesial and temporolateral cortex, right
      posterior cingulate areas, right insula, and right prefrontal areas. The right
      temporomesial activation included hippocampus, parahippocampus, and amygdala.
      These results suggest that a right hemispheric network of temporal, together with
      posterior, cingulate, and prefrontal, areas is engaged in the ecphory of affect
      laden autobiographical information.

PMID- 8753889
TI  - Excitatory actions of GABA after neuronal trauma.
AB  - GABA is the dominant inhibitory neurotransmitter in the CNS. By opening Cl-
      channels, GABA generally hyperpolarizes the membrane potential, decreases
      neuronal activity, and reduces intracellular Ca2+ of mature neurons. In the
      present experiment, we show that after neuronal trauma, GABA, both synaptically
      released and exogenously applied, exerted a novel and opposite effect,
      depolarizing neurons and increasing intracellular Ca2+. Different types of trauma
      that were effective included neurite transection, replating, osmotic imbalance,
      and excess heat. The depolarizing actions of GABA after trauma increased Ca2+
      levels up to fourfold in some neurons, occurred in more than half of the severely
      injured neurons, and was long lasting (>1 week). The mechanism for the reversed
      action of GABA appears to be a depolarized Cl- reversal potential that results in
      outward rather than inward movement of Cl-, as revealed by gramicidin-perforated
      whole-cell patch-clamp recording. The consequent depolarization and resultant
      activation of the nimodipine sensitive L- and conotoxin-sensitive N-type voltage
      activated Ca2+ channel allows extracellular Ca2+ to enter the neuron. The long
      lasting capacity to raise Ca2+ may give GABA a greater role during recovery from
      trauma in modulating gene expression, and directing and enhancing outgrowth of
      regenerating neurites. On the negative side, by its depolarizing actions, GABA
      could increase neuronal damage by raising cytosolic Ca2+ levels in injured cells.
      Furthermore, the excitatory actions of GABA after neuronal injury may contribute
      to maladaptive signal transmission in affected GABAergic brain circuits.

PMID- 8753890
TI  - Induction of hebbian and non-hebbian mossy fiber long-term potentiation by
      distinct patterns of high-frequency stimulation.
AB  - The synapse made by hippocampal mossy fibers onto pyramidal neurons of
      hippocampal area CA3 displays a form of long-term potentiation (LTP) that is
      independent of the activation of NMDA receptors. Considerable controversy exists
      as to whether the induction of mossy fiber LTP requires postsynaptic activation
      and, thus, whether mossy fiber LTP is Hebbian or non-Hebbian. Here we report the
      induction of both Hebbian and non-Hebbian forms of long-term potentiation at the
      mossy fiber-CA3 synapse in in vitro slice preparation. These two forms of
      potentiation can be induced selectively by different induction conditions.
      Sustained presynaptic activation is sufficient to induce the non-Hebbian form of
      mossy fiber LTP, whereas brief presynaptic activation coincident with
      postsynaptic depolarization is required to induce the Hebbian form. We suggest
      that non-Hebbian forms of plasticity may play an important role in dynamically
      regulating the thresholds for inducing Hebbian forms of plasticity.

PMID- 8753891
TI  - Binaural cross-correlation predicts the responses of neurons in the owl's
      auditory space map under conditions simulating summing localization.
AB  - Summing localization describes the perceptions of human listeners to two
      identical sounds from different locations presented with delays of 0-1 msec.
      Usually a single source is perceived to be located between the two actual source
      locations, biased toward the earlier source. We studied neuronal responses within
      the space map of the barn owl to sounds presented with this same paradigm. The
      owl's primary cue for localization along the azimuth, interaural time difference
      (ITD), is based on a cross-correlation-like treatment of the signals arriving at
      each ear. The output of this cross-correlation is displayed as neural activity
      across the auditory space map in the external nucleus of the owl's inferior
      colliculus. Because the ear input signals reflect the physical summing of the
      signals generated by each speaker, we first recorded the sounds at each ear and
      computed their cross-correlations at various interstimulus delays. The resulting
      binaural cross-correlation surface strongly resembles the pattern of activity
      across the space map inferred from recordings of single space-specific neurons.
      Four peaks are observed in the cross-correlation surface for any nonzero delay.
      One peak occurs at the correlation delay equal to the ITD of each speaker. Two
      additional peaks reflect "phantom sources" occurring at correlation delays that
      match the signal of the left speaker in one ear with the signal of the right
      speaker in the other ear. At zero delay, the two phantom peaks coincide. The
      surface features are complicated further by the interactions of the various
      correlation peaks.

PMID- 8753892
TI  - [Multiple nosocomial infections. An incidence study].
AB  - BACKGROUND: Some studies point out that around 30%-50% of the nosocomial
      infections (NI) are multiple (MNI) and are found in 21%-30% of the patients with
      NI. The significance of these data and their potential consequences have led the
      authors to perform this study. PATIENTS AND METHODS: A longitudinal descriptive
      study was carried out on the incidence and characteristics of NI (MNI and single
      nosocomial infection [SNI]) in 26,977 patients admitted to a county hospital from
      1991 to 1993. RESULTS: NI was detected in 1,246 patients with 31% presenting MNI
      appearing in 15% of the patients. MNI predominated in males, had a mean age were
      5 to 12 years higher than the patients with SNI with a mean hospital stay of
      between 13-28 days more than the SNI group. The MNI were significantly less
      frequent in the Urology, Gynecology and Obstetrics Departments and were more
      frequent in the Intensive Care Unit. The localization of the infection varied
      significantly among the patients with one or several infections. Bacteremia,
      pneumonia and soft tissue infections were significantly more frequent in MNI
      patients. CONCLUSIONS: Multiple nosocomial infections are frequent and their
      basic characteristics are significantly different from those of single nosocomial
      infections. The patients who acquire SNI should be carefully followed to avoid
      the appearance of MNI.

PMID- 8753893
TI  - [The assessment of functional status in hospitalized elderly patients: the
      Plutchik scale].
AB  - BACKGROUND: To study the usefulness of the Plutchik Scale to measure functional
      capacity in daily activities of hospitalized elderly patients. PATIENTS AND
      METHODS: A sample of 300 patients stratified by age and sex (111 male and 189
      female), mean age 81 years, hospitalized in the Geriatric Unit, was selected from
      all the patients admitted to our Unit along the year 1994 (n = 974, mean length
      of stay in acute beds 15 days, in convalescent beds 57 days, total 19 days).
      Scores of patients in the Plutchik Scale, Katz Activities of Daily Living and
      Barthel ADL Index were obtained. Ninety seven of the subjects were rated by two
      independent observers. RESULTS: The kappa statistic of interrater reliability in
      Plutchik Scale scoring was high (0.807). There was a good correlation between the
      three instruments at cut-points for autonomy/dependence: 0.824 for cut-points 4/5
      in Plutchik Scale and 2/3 in Katz Activities of Daily Living; 0.846 for cutpoints
      4/5 in Plutchik Scale and 55/60 in Barthel ADL Index (p < 0.01). The coefficient
      alpha (Cronbach) in Plutchik Scale was 0.876 and the standardized alpha 0.868,
      which reflect that the Plutchik Scale is internally consistent. By factor
      analysis one factor was obtained explaining 58% of the variance. The factor
      showed the highest correlation with "washing/dressing" (0.861) and lowest with
      "vision" (0.349). CONCLUSIONS: The Plutchik Scale is a good instrument for
      measuring functional capacity in hospitalized elderly patients.

PMID- 8753894
TI  - [The determination of monoclonality in B-cell lymphomas using the polymerase
      chain reaction technic on paraffin-embedded material].
AB  - BACKGROUND: Clonal rearrangements of immunoglobulin are useful in the diagnosis
      of B-cell lymphomas. The value of the polymerase chain reaction (PCR) with
      consesuated primers in the variable (V) and joining (J) region is now well
      established. METHODS: Forty cases of B-cell lymphomas and 10 patients with
      reactive lymphoid proliferations have been studied. All cases were studied with
      two different semiacotated techniques, with similar primers in the J region (LJH
      and VLJH) and changing the primers of the V region (Fr2A and Fr3A). RESULTS: A
      100% specificity and positive predictive value were obtained with both
      techniques. The sensitivity was 90% with Fr2A and 82% with Fr3A, but in 20% of
      the studies with Fr2A the extracted DNA was insufficient to perform the study
      while it could be done with Fr3A in all cases. The negative predictive value was
      76% with Fr2A and 58% with Fr3A. CONCLUSIONS: Both techniques showed a good
      sensitivity, optimal specificity and positive predictive value, with low negative
      predictive value. Although the results are somewhat higher with Fr2A, this
      technique needs well preserved DNA and it can be an important set back when we
      deal with formaldehyde fixed, paraffin embedded tissues.

PMID- 8753895
TI  - [Multiple nosocomial infections: more of the same].

PMID- 8753896
TI  - [The use of high-dose chemotherapy in the treatment of breast cancer].

PMID- 8753897
TI  - [The pathogenesis and treatment of the hemostatic disorder in acute promyelocytic
      leukemia].

PMID- 8753898
TI  - [Churg-Strauss vasculitis: recall and update].

PMID- 8753899
TI  - [Fever, dyspnea and palpitations in a 53-year-old woman].

PMID- 8753901
TI  - [Permanent hypothyroidism after interferon-alpha treatment in chronic hepatitis
      C].

PMID- 8753902
TI  - [The germinal function index in the infertile male: lactate dehydrogenase-C4
      activity in the testis].

PMID- 8753903
TI  - [Toxic habits in adolescents].

PMID- 8753905
TI  - [Basis for a hospital registry of acute myocardial infarction in Spain. The
      PRIAMO study. Project of a Hospital Registry of Acute Myocardial Infarction].
AB  - BACKGROUND AND OBJECTIVES: Information on the management of myocardial infarction
      in Spain in scarce. PRIAMHO (Proyecto de Registro de Infarto Agudo de Miocardio
      Hospitalario) study is aimed at developing standardized methods to allow the
      registration of characteristics and management of patients discharged with a
      diagnosis of myocardial infarction. Methods and results of the pilot study are
      presented. METHODS: In the present collaborative study with one-year follow-up,
      all patients diagnosed with myocardial infarction discharged from 33 Spanish
      hospitals are registered for one year including their demographic, clinical and
      outcome characteristics, as well as details on their management when admitted to
      a coronary care unit. Standardized definitions of diagnosis and measurements are
      used. Confidentiality of patients' identity and anonymous participation of each
      center are also warranted. RESULTS: The 33 participant coronary care units,
      covering some 10,000,000 people, admitted on average 83.9% of myocardial
      infarction patients of their hospital. In 16 participating centers there is a
      laboratory of hemodynamics and in 11 coronary surgery. During the pilot study,
      606 patients were discharged from the participating coronary care units where the
      case-fatality, rate was 10.3%. While 19.8% of patients developed left heart
      failure, 44.1% received thrombolytic therapy. The delay between onset of symptoms
      and first monitoring was approximately 6 hours, and thereafter admission to the
      coronary unit about 3 hours. CONCLUSION: PRIAMHO study will allow to establish of
      the fundamentals for developing a nation-wide myocardial infarction register and
      will provide an accurate perspective of the characteristics and management of
      this disease in Spain.

PMID- 8753906
TI  - [Neurohormonal factors in heart failure (and III)].
AB  - Heart failure is a physiopathological condition, with an increasing incidence and
      prevalence, involving the action of a series of mechanisms known as
      "compensators", which are phylogenetically ready to normalize minute volume and
      blood pressure. These mechanisms include the activation of a series of
      neurohormonal systems: the sympathetic nervous system, the aldosterone renin
      angiotensin system, vasopressin arginine, endothelin, which are basically
      vasoconstrictors, with the counterpoint of other vasodilator systems, such as the
      endothelial relaxation factor, certain prostaglandins and the bradykinin
      kallikrein system, which modulate global response. The authors review the
      physiopathology of each of these system, as well as their significance in the
      diagnosis and prognostic evaluation of heart failure. We analyze the possible
      deleterious effects of neurohormonal activation, anatomically and at
      cardiovascular function level, and try to determine if they are capable of
      explaining the evolution and progression of heart failure, in a truly vicious
      circle, up until the irreversible heart failure phase. We review the current
      importance of the inhibition of the aldosterone renin-angiotensin system in the
      prophylaxis and treatment of heart failure. Furthermore, we describe the present
      day value of the inhibition of the sympathetic nervous system in some forms of
      heart failure. We also analyze the different pharmacological treatments for heart
      failure: diuretics, inotropic agents, vasodilators (in their different
      pharmacological types), paying particular attention to their action on
      neurohormonal systems and their implications in the prognosis and evolution of
      heart failure.

PMID- 8753907
TI  - [Obstructive and non-obstructive hypertrophic cardiomyopathy: clinical,
      electrocardiographic, and echocardiographic differences].
AB  - AIM: The purpose of the study was to analyse echocardiographic,
      electrocardiographic and clinical variables in patients with hypertrophic
      cardiomyopathy, as well as to compare the possible differences between the non
      obstructive (NOHCM) and the obstructive form (OHCM). METHOD: 44 consecutive
      patients were studied and diagnosed with hypertrophic cardiomyopathy (NOHCM 26
      and OHCM 18). The following variables were analysed: 1) echocardiographic: right
      ventricle (RV), interventricular septum (IVS), posterior wall (pW), telediastolic
      and telesystolic diameter of the left ventricle (TDD-LV and TSD-LV), size of the
      left atrium (LA), systolic anterior motion of the mitral valve (SAM), mitral
      insufficiency and direction of the jet (MI and MIpW), mitral anular calcium
      (MAC), filling pattern (A > E); 2) electrocardiographic: repolarization disorders
      (RD), left ventricular hypertrophy (LVH), negative "T" waves in the precordial
      leads (T-), pathological "q" waves, super or ventricular arrhythmias (SA or VA),
      short PR, right or left bundle branch block (RBBB and LBBB), and 3) clinical:
      presence of dyspnea, angina, syncope, palpitations and response to treatment with
      beta-blockers (B-b) or Calcium-antagonists (C-A). RESULTS: There were no
      differences in age or sex between the obstructive and non-obstructive groups: 1)
      echocardiographic differences: there were none in RV, pW, TDD-LV, LA nor A > E
      wave. Significant differences were found (p < 0.05) in the rest of the variables;
      IVS (16 +/- 3 mm in NOHCM vs 22 +/- 5 mm in OHCM), TSD-LV (26 +/- 5 mm in NOHCM
      vs 22 +/- 6 mm in OHCM), SAM (38% in NOHCM vs 89% in OHCM), MI (19% in NOHCM vs
      78% in OHCM), MIpW (20% in NOHCM vs 79% in OHCM), MAC (15% in NOHCM vs 44% in
      OHCM); 2) electrocardiographic differences: there were none in the presence of
      RD, pathological "q", VA, short PR, RBBB nor LBBB. The presence of "T" negatives
      was on the limit of significance in the precordial leads (31% in NOHCM vs 11% in
      OHCM; p = 0.09). Differences were found in the rest of the variables; LVH (58% in
      NOHCM vs 83% in OHCM), SA (50% in NOHCM vs 17% in OHCM); 3) clinical differences:
      there were none in the presence of dyspnea, angina, syncope or palpitations.
      Differences were found in the improvement with treatment; B-b (60% in NOHCM vs
      57% in OHCM), C-A (100% in NOHCM vs 100% in OHCM). CONCLUSIONS: 1) in our
      patients, the most frequent cardiomyopathy is the non-obstructive one, with no
      predominance of age or sex; 2) in OHCM, IVS is much wider, with smaller TSD-LV,
      there is a greater incidence of MI, generally directed towards the posterior wall
      of the left atrium, and a larger tendency to calcify the mitral annulus; 3) the
      most frequent electrocardiographic abnormality is the alteration of
      repolarization. NOHCM has a greater incidence of SA and a lower degree of LVH
      with more prevalence of negative "T" waves in the precordial leads; 4) there are
      no clinical parameters differentiating the two groups, although the sustained
      improvement obtained with treatment is more likely to be produced by the calcium
      antagonists than by beta-blockers in both types of cardiomyopathy.

PMID- 8753908
TI  - [Complications at the first month following various types of intracoronary
      stents, implanted with high pressure without intracoronary ultrasonography or
      anticoagulation].
AB  - BACKGROUND: Coronary stents have proved their efficacy in bail-out situations and
      restenosis. Nevertheless, the high incidence of subacute thrombosis and vascular
      and bleeding complications limits its use. OBJECTIVES: To evaluate the clinical
      complications during the first month of three different types of stents,
      implanted with high pressure, without ultrasound guidance or anticoagulation.
      PATIENTS AND METHODS: All stents were implanted in arteries of 3 mm or more.
      After implantation, all stents were dilated between 15-17 atmospheres, aiming to
      a residual stenosis lower than 10%. After implantation, all patients received
      aspirin indefinitely and ticlopidine 250 mg twice daily for one month. The
      initial success, the ischemic complications (death, myocardial infarction and
      emergency surgery), acute and subacute thrombosis and vascular and hemorrhagic
      complications were evaluated. The evaluation was done following the procedure,
      prior to discharge from the hospital and at 1 month follow-up. RESULTS: In 49
      patients, 51 stents were implanted. 70% had unstable angina. In one case the
      stent was implanted after primary PTCA. In 17.6%, the stent was implanted in a
      bail-out situation. Of the 51 stents, 32 were Palmaz-Schatz, 12 Wiktor and 7
      Gianturco-Roubin. The initial success was 100%. There were no deaths, AMI, nor
      emergency surgeries in the first month. There was no case of acute or subacute
      thrombosis. There were 2 minor complications; one vascular: a pseudoaneurysm, and
      another hemorrhagic: an inguinal hematoma. Neither case needed surgery nor blood
      transfusion. All patients were discharged within 48 hours. CONCLUSION:
      Implantation of stents with high pressures, in spite of not using guidance
      ultrasound nor anticoagulation, is safe and effective, with a clear decrease in
      vascular complications, and without an increase in the incidence of acute or
      subacute thrombosis.

PMID- 8753909
TI  - [Coronary endoprosthesis (stents) implanted without coumadin administration: one
      year's experience].
AB  - BACKGROUND AND OBJECTIVES: Subacute occlusion and bleeding complications have
      been the major limitations of coronary stenting. Several authors have suggested
      the nonessential role of oral anticoagulation to prevent occlusions. METHODS: We
      treated 121 patients (125 stent procedures with initial angiographic success)
      with the following regimen: heparin 10-20,000 IU i.v. and ASA 325 mg i.v. during
      the procedure, followed by ASA 125-325 mg/day/6 months and ticlopidine 250-500
      mg/day/3 months. 40 patients were also treated with enoxaparine (14,000 IU/day,
      median) for 10 days. RESULTS: 172 stents (119 Palmaz-Schatz, 35 Wiktor and 18 of
      other types) were implanted in 148 lesions (in 45 cases with non-occlusive
      dissection or suboptimal results and the rest electively). Most of the stents
      were deployed at high pressure (median 14 atm.). The procedure was ended when the
      stent expansion was considered as optimal by angiography and/or intravascular
      ultrasound. No patient developed signs of subacute occlusion at follow-up (30-441
      days). 2 patients developed non-Q wave myocardial infarction (occlusion of side
      branches). The rates of bleeding and vascular complications were 0.8% and 1.6%,
      respectively. CONCLUSIONS: Coronary stenting with high pressure dilatation and
      without subsequent anticoagulation seems to be associated with low rates of
      subacute occlusion and bleeding or vascular complications.

PMID- 8753910
TI  - [Fetal supraventricular tachycardia].
AB  - BACKGROUND: Fetal supraventricular tachycardia is an infrequent and difficult to
      manage disease. Several therapeutic approaches have been proposed. We report our
      experience in its diagnosis and management. OBJECTIVES: Evaluation of the
      clinical features of fetal supraventricular tachycardia and efficacy of maternal
      and fetal medications in use for treatment. Immediate neonatal evolution is
      commented on. A therapeutic schema is proposed. PATIENTS: Nineteen fetuses with
      echocardiographically (M-mode and/or Doppler two dimensionally oriented)
      supraventricular tachycardia were diagnosed. RESULTS: Mean gestational age was 32
      weeks; 8 fetuses had developed hydrops; 3 patients had dilated cardiomyopathy
      (two of them were hydropic). Two cases were prenatally diagnosed as atrial
      flutter (both of them without hydrops). Sixteen fetuses received transplacentary
      treatment: 8 with digital, 6 more associated with flecainide, direct
      administration of amiodarone to the fetus was added in two cases. Three patients
      died during follow-up (one postnatally, at third week of life), all of them had
      developed hydrops; arrhythmia characteristics were unmodified in three and
      control of cardiac rhythm was achieved in ten cases. CONCLUSIONS: In the majority
      of cases there are no cardiac malformations associated. It is possible to control
      the tachycardia, even if hydrops is present. It is not indicated to abbreviate
      the gestation. First election drugs are maternal digoxin and flecainide, they do
      not produce significant fetal or maternal secondary effects. Occasionally it is
      necessary to add or to change to other drugs or to propose more aggressive
      approaches.

PMID- 8753911
TI  - [Influence of coronary anatomy on the anatomic repair of transposition of great
      arteries].
AB  - INTRODUCTION: The anatomic diversity of the coronary artery and the alignment of
      the aortic and pulmonary valves have special importance on the surgical anatomic
      correction of the transposition of the great arteries and double outlet of the
      right ventricle, because of their repercussions on surgical technique and the
      effect on the operative results. OBJECTIVE: To determine the coronary artery
      pattern; the aortic and pulmonary valve alignment, and their effects on the
      surgical results in 57 patients submitted to anatomic correction in our hospital.
      METHOD: We used the Yacoub and Radley-Smith patterns in order to classify the
      different coronary distributions. The relation between the coronary pattern and
      degree of alignment with surgical difficulty and the mortality rate was examined.
      The coronary pattern established by echocardiography was compared with the
      surgical findings in the last 16 patients. RESULTS: 31 patients belonged to group
      A, 3 to B, 2 to C, 19 to D and 2 to E. There was no difference in the
      extracorporeal circulation time among the groups, although the difficulty in the
      coronary transfer was not the same among them. Type E mortality rate was 50%,
      type B 33%, and type D 5.2%. There were no deaths in the other groups.
      Malalignment was found in the three patients who died. The coronary pattern found
      by echocardiography was confirmed in 13 patients whose images were quite clear.
      CONCLUSIONS: Coronary pattern and the malignment affect both surgical difficulty
      and mortality rate of patients undergoing anatomic correction. Bidimensional
      echocardiography is useful to demonstrate the different coronary patterns in most
      cases.

PMID- 8753912
TI  - [Cardiomyopathy (X). Clinical approach to the patient with hypertrophic
      cardiomyopathy].
AB  - Hypertrophic cardiomyopathy is a clinical and anatomofunctional entity that
      determines a series of hemodynamic consequences closely related to sintomatology.
      Left ventricular hypertrophic, subaortic stenosis, diastolic dysfunction and
      myocardial ischemia are the different pathophysiology mechanisms that generate
      similar clinical manifestations. Sintomatology defines two groups of patients
      with different profiles and clinical management. Ventricular arrhythmias are not
      uncommon and the forms that imply a darkest prognosis are supported symptomatic
      ventricular tachycardia and the induced ventricular tachycardia in patients that
      have suffered a cardiac arrest or have had syncopes. Basic explorations in all
      patients, in addition to physical examination, chest radiography and rest
      electrocardiogram, are Doppler echocardiography and Holter. Other explorations,
      such as Tallium-201 stress test, tilt test, electrophysiological and hemodynamic
      studies, are rationalized according to risk profile, sintomatology and responses
      to indicated treatment. In general, prognosis in asymptomatic patients is good
      and complex explorations are not justified nor are preventive character
      treatments. Symptomatic patients who have a higher risk must be studied more
      closely, and frequently require complex and invasive explorations. They also need
      pharmacological treatment and often more invasive therapeutical options, DDD
      pacemakers or surgery, if those fail.

PMID- 8753913
TI  - [Differential diagnosis of acute myocardial infarction caused by electrocution].
AB  - Electrical injury can affect many organ systems, it seems that the damage results
      from the conversion of electrical energy into heat. Electrical injuries to the
      heart are far less frequent and thus, less known. Additionally, it is very
      difficult to interpret electrocardiographic and enzymatic changes, which are, in
      other situations, diagnostic of a myocardial infarction. We report two cases of
      young men without coronary risk factors. They present a rise in enzyme levels and
      electrocardiographic changes suggestive of acute myocardial infarction after
      alternating current electrocution. The difficulties in evaluating the myocardial
      damage in these situations are also discussed. We recommend ECG monitoring and
      long-term cardiac evaluation of these patients.

PMID- 8753914
TI  - [Subtotal thyroidectomy. A treatment to keep in mind in amiodarone-induced
      thyrotoxicosis].
AB  - Amiodarone is an antiarrhythmic drug, frequently used in cardiology, which may
      produce secondary effects on the thyroid function. These effects can range from
      subtle changes in peripheral hormones without clinical manifestations, to severe
      forms of hypothyroidism or hyperthyroidism. The evolution of amiodarone-induced
      hyperthyroidism can be mild, requiring only the withdrawal of the drug, or very
      severe, requiring an aggressive therapy with multiple drugs which may in some
      cases be fatal in spite of this therapy. Recently, the increase in the usage of
      this drug has produced reports of severe amiodarone-induced-thyrotoxicosis
      requiring surgery in some cases (subtotal or total thyroidectomy). A case of
      amiodarone-induced-thyrotoxicosis in its more aggressive form, which required
      intensive pharmacological treatment ultimately combined with surgery, is
      presented here.

PMID- 8753916
TI  - [Mitral valvuloplasty in the elderly].

PMID- 8753915
TI  - [Doppler ultrasonography diagnosis of right ventricular outflow tract obstruction
      caused by mediastinal tumor and its reversibility after treatment].
AB  - Doppler-echocardiography has proved useful in the assessment of mediastinal
      masses. We present the case of a young man with fever and new systolic murmur.
      Echocardiographic examination revealed a paracardiac mass compressing the right
      ventricular outflow tract and Doppler flow study detected marked acceleration in
      luminal narrowing. Complete remission of the tumour was obtained with subtotal
      resection and chemotherapy. Histological diagnosis was of embryonary carcinoma
      with areas of endodermic sinus. A new Doppler-echocardiography study showed
      disappearance of both the mass and the compression and showed normal right
      ventricular outflow tract flow.

PMID- 8753917
TI  - [Pain and anesthesiologists].

PMID- 8753918
TI  - [Changes in the immunologic status related to the duration of the
      anesthesia/surgery procedure].
AB  - OBJECTIVE: To study the effect of the trauma of anesthesia and surgery, and their
      duration, on immune status. PATIENTS AND METHODS: Fifty patients undergoing
      cholecystectomy were studied in 2 groups. In group A surgery was of short
      duration ( < 60 min) and in group B surgery was longer ( > 60 min). Immunological
      analysis were performed at 5 times: t0 (before surgery), t1 (1 h), t2 (24 h), t3
      (4 days) and t4 (7 days). RESULTS: Group A patients experienced a non significant
      decrease in T lymphocytes, activated T lymphocytes and B lymphocytes, with levels
      returning to normal after 7 days. T-suppression, on the other hand, decreased
      significantly in the first 24 h, but gradually returned to normal after 7 days. T
      lymphocytes, activated T lymphocytes and B lymphocytes decreased in group B and
      regressed after 7 days. The population of B lymphocytes decreased significantly
      and had not fully recovered 7 days after surgery. CONCLUSIONS: The act of
      anesthesia/surgery depresses immune response in function of duration, with the
      effect being greater when surgery lasts longer.

PMID- 8753919
TI  - [Impact of anesthetic technic (general anesthesia versus intradural anesthesia)
      on the immune status].
AB  - OBJECTIVE: To study changes in the immune system appearing after general and
      regional (intradural anesthesia). PATIENTS AND METHODS: Fifty patients scheduled
      for elective surgery to repair inguinal hernias were studied. The patients were
      randomly assigned to 2 groups: group A patients received general anesthesia and
      group B patients received intradural anesthesia. Blood was extracted 5 times to
      determine levels of lymphocytes, activated T cells and B lymphocytes, and T
      suppressant activity: t0 (before surgery), t1 (1 h), t2 (4 h), t3 (24 h) y t4 (7
      days). RESULTS: The patients in group A showed slight increases in T lymphocytes,
      activated T lymphocytes and B lymphocytes, whereas T-suppressant activity
      decreased significantly. All lymphoid population decreased in group B. Baseline
      levels had recovered in both groups by 7 days after surgery. CONCLUSION:
      Anesthetic procedures have an effect on immune responses but the impact is only
      temporary.

PMID- 8753920
TI  - [Comparative study of the treatment of postoperative pain in function of the
      surgical service].
AB  - HYPOTHESIS AND OBJECTIVES: A high level of pain has been observed among surgical
      patients and it has been suggested that surgical specialty may be an important
      factor in pain, although no relation has been conclusively demonstrated. In this
      study we compared the characteristics of postoperative pain and pain treatment
      given in several surgical services. PATIENTS AND METHODS: We studied 249 patients
      in orthopedic surgery and traumatology (OST, n = 95), general surgery (GS, n =
      66), gynecology and obstetrics (GO, n = 51), urology (URO, n = 16), vascular
      surgery (VS, n = 9), ophthalmology (OPH, n = 7), otorhinolaryngology (ORL, n =
      5). The characteristics of analgesic treatment (type of prescription, drug,
      route, dose and compliance) were recorded, as were degree of pain expressed on a
      visual analog scale and a verbal assessment scale 24 h after surgery, and level
      of patient satisfaction with the analgesic treatment. RESULTS: Thirty percent of
      the patients reported moderate to unbearable pain the day after surgery. Severe
      pain was most common in OST patients. Analgesics, mainly diclofenac (52%) and
      pethidine (36%), were prescribed by protocol for 93% of patients. Although there
      were differences among the various services, compliance with diclofenac
      prescription was better; compliance was high among GO patients for both drugs.
      Over half the patients reported having had severe or unbearable pain during the
      hours following surgery. Most said relief was sufficient or high (55%) with
      treatment and described themselves as satisfied or very satisfied (62%) with the
      analgesic received. Surgery on extremities was the most painful and generated the
      greatest dissatisfaction. CONCLUSIONS: This study suggests that type of surgery
      may condition the prevalence of and severity of postoperative pain. Although type
      of surgery and location are important factors, there are sufficient differences
      and deficiencies in treatment to explain, at least partly, the variation
      observed.

PMID- 8753921
TI  - [Errors in bibliographic references in the Revista Espanola de Anestesiologia y
      Reanimacion: retrospective study of 1994].
AB  - OBJECTIVES: To evaluate the accuracy of bibliographic references in REVISTA
      ESPANOLA DE ANESTESIOLOGIA Y REANIMACION (REDAR) and compare it with other
      Spanish and international journals. MATERIAL AND METHODS: One hundred references
      were selected at random from those published in REDAR during 1994. A citation was
      considered correct if there were no differences between it and the original
      article in any of 6 standard citation times, and if it complied with REDAR
      citation style. A citation was considered incorrect if there were in fact
      differences or if REDAR style was not followed. Errors that interfered with
      direct access to the original were considered serious. Also considered serious
      were the omission of the first author. RESULTS: Some type of error was detected
      in 53.9% of the references. Twelve contained a serious error, which on 5
      occasions impeded finding the original article and on 6 occasions made direct
      access difficult. The first author was missing in 1 citation. Errors were found,
      in order of decreasing frequency, in authors, article titles, journal title,
      volume, pages and year. A single error was found in 28 citations, 2 were found in
      12, 3 were found in 2 and more than 3 were found in 1. CONCLUSIONS: REDAR's rate
      of error in references is comparable to the rates of other Spanish journal, but
      it is nearly double that of international journals in anesthesiology with higher
      impact factors (Anesthesiology, Canadian Journal of Anaesthesia). An effort must
      be made by authors and editors to remedy the situation.

PMID- 8753922
TI  - [Hemodynamic response to intubation with Macintosh and McCoy blades].
AB  - INTRODUCTION: The McCoy laryngoscope incorporates a modification of the Macintosh
      blade designed to facilitate laryngoscopy and difficult intubation. One end is
      articulated to allow better viewing of the larynx. Use of this blade reduces
      pressure placed on tissues in the supraglottic area during laryngoscopy.
      OBJECTIVE: We designed this study to compare the hemodynamic repercussions of
      laryngoscopy and tracheal intubation (LTI) performed with either a Macintosh or
      the McCoy blade. PATIENTS AND METHOD: Sixty ASA I-II patients scheduled for
      elective surgery requiring LTI were randomly assigned to 2 groups of 30 patients
      each. In both groups anesthetic induction was achieved with 0.04 mg.kg-1
      midazolam, 0.002 mg.kg-1 fentanyl, 2 mg.kg-1 propofol and 0.1 mg.kg-1 vecuronium.
      In group 1 LTI laryngoscopy and intubation were performed using the Macintosh
      size 3 blade and in group 2 the McCoy size 3 blade was used. Systolic and
      diastolic arterial pressures and heart rate were recorded in each patient before
      anesthetic induction (baseline), 1 minute after induction and 5 minutes after
      start of LTI. RESULTS: We found no significant differences between the 2 groups
      at any of the recording times. CONCLUSION: The data obtained do not allow us to
      assert that there is any difference in hemodynamic response to LTI associated to
      type of blade used.

PMID- 8753923
TI  - [Amniotic fluid embolism: review].
AB  - The amniotic fluid embolism, is a very uncommon syndrome but because of its
      severity and high mortality, it is interesting to study and to get a deep
      knowledge of its etiopathogenia and physiopathology. In this article, we revise
      the actually purposed pathogenic mechanisms, specially the humoral mechanisms in
      front of mechanical, as it was defended a few years ago. The diagnostic of this
      syndrome, is an interesting question, because it is not only pathology, actually
      it trends to immunologic diagnosis. The amniotic fluid embolism, interests to
      anesthesiologist and its differences in cardiopulmonary resuscitation in the
      pregnant woman too. All these data are discussed in our article, as much as
      treatment, that is based upon haemodinamics and cardiopulmonary resuscitation.

PMID- 8753924
TI  - [Anesthetic treatment of periodic familial hypokalemic paralysis. Report of a
      case].
AB  - Periodic familiar hypopotassemic paralysis (PFHP) is a rare dominant autosomally
      transmitted genetic disease characterized by intermittent attacks of muscle
      weakness. A patient with PFHP was successfully given general anesthesia for 2
      operations using atracurium as the muscle relaxant. For a third operation he was
      given a paravertebral block.

PMID- 8753925
TI  - [Effectiveness of propofol in pediatric magnetic resonance].

PMID- 8753926
TI  - [A case of PetCO2 increase in laparoscopic surgery: CO2 embolism?].

PMID- 8753927
TI  - [Anesthetic implications in Morquio syndrome].

PMID- 8753928
TI  - [Pulmonary lymphangiomyomatosis. Report of a case].

PMID- 8753929
TI  - [Cesarean section in pregnancy with undiagnosed pheochromocytoma].

PMID- 8753930
TI  - [Uterine inversion: a severe obstetric complication].

PMID- 8753931
TI  - [Transesophageal echocardiography in the intraoperative management of a pregnant
      patient with suspected vena cava thrombosis].

PMID- 8753932
TI  - Hebb's concept of cell assemblies and the psychophysiology of word processing.
AB  - Hebb's brain-theoretical approach suggests that tightly connected networks of
      neurons, Hebbian cell assemblies, are the building blocks of cognitive functions.
      These assemblies are not necessarily restricted to a small cortical locus but may
      be dispersed over distant cortical areas. Assemblies with different topographies
      can be postulated for different kinds of words, such as meaningful content versus
      grammatical function words or words eliciting motor versus visual associations.
      Evidence from evoked potentials and gamma-band electrocortical responses elicited
      by lexical material supports a cell assembly model of language and other higher
      cognitive functions.

PMID- 8753933
TI  - Meta-analysis of P300 normative aging studies.
AB  - The theoretical and empirical backgrounds for the utility of the P300 event
      related potential (ERP) as a measure of cognitive aging are summarized. P300
      latency data from 32 different normative aging studies are then reviewed and
      assessed with meta-analytic procedures. Evaluation of moderator variables
      indicates that sample characteristics, stimulus factors, and task conditions
      contribute significantly to the "normal" change in peak latency that occurs with
      aging. These findings are critiqued in the context of previous reports, and
      implications are outlined for future applications of ERPs to normative aging. It
      is concluded that P300 latency can provide useful information about cognitive
      aging but that specific variables must be considered to obtain more precise
      results.

PMID- 8753934
TI  - Acute effects of caffeine on selective attention and visual search processes.
AB  - The influence of a single dose of caffeine was evaluated in focused and divided
      attention conditions of a visual selective search task in which subjects had to
      perform controlled search processes to locate a target item. Search processes
      were manipulated by varying display load. A dose of 3 mg/kg body weight caffeine
      or lactose, dissolved in a cup of decaffeinated coffee, was administered double
      blindly and deceptively to overnight abstinent coffee drinkers. Behavioral
      measures were supplemented by event-related potentials (ERPs). Subjects reacted
      faster in the caffeine condition. The P3b peak latency decreased after caffeine
      in the low display load condition and in the focused attention condition,
      indicating that the effects of caffeine are dependent on the number of relevant
      display items, not on the total number of display items presented. Search
      processes, as reflected in a negative ERP deflection, were not affected by
      caffeine.

PMID- 8753935
TI  - On the validity of estimating EEG correlation dimension from a spatial embedding.
AB  - We demonstrate by using simulations that spatial embedding of single-variable
      time series data does not reliably reconstruct state-space dynamics. Instead,
      correlation dimension estimated from spatially embedded data is largely a measure
      of linear cross-correlation in the data set. For actual electroencephalographic
      (EEG) data, we demonstrate a high negative correlation between spatial
      correlation dimension and the average amount of lag-zero cross-correlation
      between "nearest-neighbor" embedding channels (the greater the cross-correlation,
      the lower the dimension). We also show that the essential results obtained from
      spatially embedding EEG data are also obtained when one spatially embeds across a
      set of highly cross-correlated stochastic (second-order autoregressive)
      processes. Although, with appropriate surrogate data, correlation dimension
      estimated from spatially embedded data detects nonlinearity, its use is not
      recommended because correlation dimension estimated from temporally embedded data
      both reconstructs state-space dynamics and, with appropriate surrogate data,
      detects nonlinearity as well.

PMID- 8753936
TI  - Processing of complex sounds in the human auditory cortex as revealed by magnetic
      brain responses.
AB  - Processing of simple and complex sounds in the human brain was compared by
      recording extracranial magnetic mismatch responses (MMNm; the magnetic
      counterpart of the mismatch negativity, or MMN) to frequency changes in these
      sounds. Generator sources, modeled as equivalent current dipoles (ECDs), of MMNm
      responses to a change in one frequency element of complex sounds (a chord and a
      serial tone pattern) were located in supratemporal auditory cortex, on average,
      10 mm medially to the source of an MMNm elicited by an identical frequency change
      in a simple tone. These results suggest that at least partially different
      supratemporal neuron populations are involved in processing changes in simple and
      complex sounds and that sensory-memory representations for these sounds may be
      located in different fields of the auditory cortex.

PMID- 8753937
TI  - The nature of the late positive complex within the olfactory event-related
      potential (OERP).
AB  - The olfactory event-related potential (OERP) has been described as being
      dependent on exogenous stimulus features, but no effort has been made to examine
      possible endogenous determinants. We wanted to separate exogenous and endogenous
      components of the OERP by using an olfactory oddball paradigm. A high
      concentration of citral was used as the target stimulus, and a low concentration
      was used as the standard stimulus. Odors were presented within a constantly
      flowing air stream. We found that the early components of the OERP (N1, P2) are
      modulated by the stimulus concentration, whereas the late positive components (P3
      1, P3-2) vary depending on the subjective stimulus significance and stimulus
      probability. It is concluded that the positive component of the OERP, which has
      been formerly explained by chemical and physical stimulus features, is actually
      determined by endogenous processes.

PMID- 8753938
TI  - Predicting sleep latency from the three-process model of alertness regulation.
AB  - This paper presents a modification of the quantitative "three-process model of
      alertness regulation" to predict sleep latency in connection with irregular
      sleep/wake patterns. This model uses a circadian and a homeostatic component
      (sleep loss) that are summed to yield predicted alertness (on a scale of 1 to 20)
      across a specified time span. The timing of sleep from two studies of irregular
      sleep were used as input to the model. The predicted alertness at bedtime was
      regressed on empirical sleep latency from two studies. The maximum R2 (0.88) was
      reached for an exponential function, with the model acrophase set to 2048. The
      predictions were cross validated on another set of sleep latency data from an
      irregular sleep study and a maximum R2 of 0.65 was obtained. In both studies, the
      prediction from the model explained more variance that did self-rated alertness
      at bedtime. Cross validation was also carried out successfully with published
      data from two studies of shift work. It was concluded that sleep latency on
      irregular schedules may be predicted with accuracy from knowledge of the prior
      sleep/wake pattern. This may have practical consequences for rest/activity
      management.

PMID- 8753939
TI  - Mixture analysis of smooth pursuit eye movements in schizophrenia.
AB  - The goal of this study was to replicate and extend previous findings indicating
      that the eye movement data of schizophrenic patients is best represented by the
      mixture of two groups, one of which has distinctly poor performance. Forty-nine
      schizophrenic patients and 32 normal controls had their smooth pursuit eye
      movements quantified by calculating the root mean square (RMS) deviation between
      the target and eye waveforms. Based on the finding of mixture in the distribution
      of RMS error, the patients were divided into low (better tracking) and high
      (worse tracking) RMS error subgroups. The high RMS error patients had abnormally
      decreased gain. Both patient subgroups had abnormally increased frequency of
      catch-up saccades and increased phase lag. Distinguishing between these two
      subgroups may be useful in clarifying the pathophysiology of abnormal pursuit and
      its relationship to heterogeneity in schizophrenia.

PMID- 8753940
TI  - Effects of interstimulus interval on scalp topographies evoked by noxious sural
      nerve stimulation.
AB  - The amplitude of the late pain-related negative-positive peak complex, which we
      have labeled SP3 (134-150 ms) and SP6 (277-331 ms), respectively, increased with
      increasing interstimulus interval (ISI). This contrasts with the nociceptive
      spinal withdrawal reflex and subjective pain rating data, which implied that
      nociceptive somatosensory processes were unaffected by ISI at stimulus levels
      that were well within the pain range. A scalp topographic analysis strongly
      suggested that none of the brain areas responsible for SP3 or SP6 are involved
      exclusively in nociception. We also observed a pain-related positive potential
      approximately 161-177 ms following sural nerve stimulation that has not been
      reported by others. A dipole source localization analysis and the effects of ISI
      and stimulus intensity on this potential suggest that it is generated by the
      response of primary somatosensory cortex neurons to inputs arising from the
      innocuous peripheral afferents and that this response is inhibited by noxious
      inputs.

PMID- 8753941
TI  - The ambulatory measurement of posture, thigh acceleration, and muscle tension and
      their relationship to heart rate.
AB  - We compared the relative ability of continuous accelerometric, electromyographic
      (EMG), and hydrostatic posture measurements to discriminate tasks involving
      variations in motor activity and posture and to predict heart rate (HR)
      variability. EMG was a more sensitive measure than accelerometry in
      differentiating the tasks. However, accelerometry and EMG explained comparable
      amounts of HR variance. The hydrostatic posture was a stable measure that clearly
      differentiated postures and explained a significant amount of HR variance but
      less than accelerometry or EMG. Accelerometric and EMG measures of motor activity
      used either alone or in combination with the hydrostatic posture are valuable in
      discriminating activities and in controlling for the effects of motor activity
      and posture on HR during ambulatory measurement.

PMID- 8753942
TI  - Conditioning with facial expressions of emotion: effects of CS sex and age.
AB  - Two experiments examined the effects of facial expressions of emotion as
      conditioned stimuli (CSs) on human electrodermal conditioning and on a continuous
      measure of expectancy of the shock unconditioned stimulus. In Experiment 1, the
      CS+ was a picture of a person displaying an angry face and CS- was a neutral
      face. For half of the subjects, the expressions were depicted by males, for the
      other half by females. Male subjects showed larger skin conductance responses to
      pictures of males than did females. The responding of female subjects was the
      same regardless of the sex of the person in the picture. In Experiment 2, the CS+
      and CS- were pictures of an angry or a happy face. For half of the subjects, the
      expressions were depicted by adult males, for the other half by preadolescent
      males. Subjects displayed greater differentiation when an adult male depicting
      anger was employed as the CS+ than when a preadolescent male depicting anger was
      the CS+. There were no differences when an adult or a child displayed happiness.

PMID- 8753943
TI  - The impact of performance uncertainty on the postimperative negative variation.
AB  - In a delayed matching-to-sample task, the impact of clear or ambiguous go versus
      clear no-go signals on the post-imperative negative variation (PINV) was examined
      in 11 patients with a chronic schizophrenic disorder (DSM-III-R) and in a control
      group of 13 healthy subjects matched to the patient sample by age, sex, and
      education. Size and spatial position of a visual S2 had to be matched to one of
      two visual patterns in the S1 presented 4 s earlier. In 96 trials, the S2 was
      identical in size with one of the two patterns of S1 (clear matching). These
      trials varied pseudorandomly, with 60 trials in which the S2 was of intermediate
      size. On a randomly interspersed additional 48 trials, an S2 differing in color
      and shape signaled no-go. The electroencephalogram was recorded from Fz, Cz, Pz,
      F3, F4, C3, C4, P3, and P4. Although groups did not differ in contingent negative
      variation amplitude, the PINV was generally more pronounced in patients than in
      controls. In both groups, ambiguity of the to-be-matched S2 produced larger PINV
      amplitudes; the no-go signal elicited only a small PINV. Differential effects of
      ambiguity and no-go on PINV amplitude and its scalp distribution suggest that
      "performance" and "action" uncertainty contribute to PINV generation and that
      thresholds for both effects are reduced in schizophrenics.

PMID- 8753944
TI  - Social support and hostility interact to influence clinic, work, and home blood
      pressure in black and white men and women.
AB  - The effects of hostility and social support on clinic, work, and home systolic
      (SBP) and diastolic (DBP) blood pressures were evaluated in 129 healthy adults.
      High hostility was related to higher SBP and DBP in Whites; low hostility was
      related to higher SBP and DBP in Blacks. These relationships were significant for
      men at home and at work and for women at screening. The relationship between low
      hostility and higher BP in Blacks was largely due to Black men who reported low
      hostility plus high anger-in (suggesting suppressed hostility). In contrast, high
      hostile Black men with high tangible support tended to exhibit lower BP than all
      other Black men. In White women, high belonging support was related to lower BP,
      independent of hostility, and low tangible support plus high hostility was
      related to higher clinic BP. In high hostile subjects, regardless of ethnicity or
      gender, high appraisal support was related to lower overall BP. These data
      suggest that the adverse BP effects of hostility and the beneficial effects of
      social support interact in a complex manner, reflecting contextual, ethnic, and
      gender specificities.

PMID- 8753945
TI  - The effect of lorazepam on memory and event-related potentials in heavy and light
      social drinkers.
AB  - To investigate the effects of heavy social drinking on sober cognitive
      processing, event-related potentials were recorded from 13 heavy social drinkers
      and 13 light social drinkers in the presence and absence of a pharmacological
      challenge (i.e., lorazepam). Event-related potentials were elicited by a task
      requiring continuous recognition memory for visually presented words. The heavy
      social drinkers exhibited shorter P2 latencies than the light social drinkers and
      decreased P300 latencies to correctly identified "old" words (i.e., words
      presented previously in the task) versus "new" words. Lorazepam increased motor
      reaction time to correctly identified old words and produced a deficit in
      recognition memory only in the light social drinkers. Light social drinkers had
      an increased P300 latency and a larger P300 amplitude to new words in the
      lorazepam treatment. The differences in cognitive functioning evident between
      heavy and light social drinkers were reflected in event-related potential
      deviations and appear to indicate a tolerance in heavy social drinkers to the
      effects of lorazepam.

PMID- 8753946
TI  - Pupillary responses index cognitive resource limitations.
AB  - Cognitive task-evoked pupillary responses reliably index information-processing
      loads. However, previous studies have reported inconsistent findings regarding
      the nature of the pupillary response when processing demands approach or exceed
      available processing resources. This condition was examined in 22 normal
      undergraduates by using pupillometric recordings during a digit span recall task,
      with 5 (low load), 9 (moderate load), and 13 (excessive load) digits per string.
      Pupillary responses increased systematically with increased processing load (to
      be-recalled digits) until the limit of available resources (memory capacity of 7
      +/- 2 digits), when they reached asymptote and then declined with resource
      overload (> 9 digits). These findings suggest that pupillary responses increase
      systematically with increased processing demands that are below resource limits,
      change little during active processing at or near resource limits, and begin to
      decline when processing demands exceed available resources.

PMID- 8753947
TI  - Naming norms for brief environmental sounds: effects of age and dementia.
AB  - Brief nontonal sounds are used in electrophysiology in the novelty oddball
      paradigm. These sounds vary in the brain activity they elicit and in the degree
      to which they can be identified, named, and remembered. Because ease of sound
      identification may influence sound processing, naming and conceptual norms were
      determined for 100 sounds for 77 young adults (Experiment 1). Naming ability
      decreases in normal and pathological aging. Therefore, norms were also derived
      for older adults (Experiment 2) and for probable Alzheimer's disease patients
      (Experiment 3). With respect to the young adults, perseverative naming behavior
      increased in these groups, and sound and picture naming performance were
      correlated. In Experiment 4, the sound-naming performance of children aged 5-6, 9
      11, and 14-16 years was compared. Name and conceptual agreements improved with
      age, whereas perseverative behavior decreased. These normative data should be
      useful in guiding sound selection in future studies and help clarify the
      relationships between sound naming and other variables, including direct and
      indirect memory performance.

PMID- 8753948
TI  - The ontogenetically earliest discriminative response of the human brain.
AB  - Speech sounds elicited electric brain responses in healthy premature infants born
      30-35 weeks after conception, demonstrating that the human brain is able to
      discriminate speech sounds even at this early age, well before term, and
      supporting previous results suggesting that the human fetus may learn to
      discriminate sounds while still in the womb. We presented preterm infants with
      stimulus sequences consisting of a repetitive vowel that was occasionally
      replaced by a different vowel. This infrequent vowel elicited a response
      resembling the adult mismatch negativity, which is known to reflect the brain's
      automatic detection of stimulus change. The present results constitute the
      ontogenetically earliest discriminative response of the human brain ever
      recorded.

PMID- 8753949
TI  - [Ivan Fedorovich Bush (1771-1843)].

PMID- 8753950
TI  - [Our experience in treating patients with embolisms of the aorta and major
      arteries of the extremities (on the centenary of the first embolectomy)].
AB  - The modern development of vascular surgery has a real possibility to reduce
      lethality and the amount of amputations in patients with embolism of the aorta
      and major arteries of the extremities. An analysis of treatment of 2042 patients
      during the recent 28 years has shown that the embolism is observed in 62,3% of
      patients with IHD and its complications, and in 34,5% in rheumatism patients, the
      arterial impassability prevailing in the abdominal aorta basin and lower
      extremity arteries (67,5%). Surgical procedures were used in 86,6% with the
      restoration of the main or collateral blood flow in 91,2% of the patients
      operated upon. Irreversible ischemia of the extremity was diagnosed in 89
      patients at admission to the hospital. For prophylactics of rethromboses and
      infection, nonmedicamentous methods of treatment played an important role and the
      amount of rethromboses was reduced to 5,5% and suppuration of the wound to 6,2%
      which resulted in low percentage of amputations (5,8%).

PMID- 8753951
TI  - [The surgical correction of pressure in the lesser circulation after extensive
      lung resections for cancer].
AB  - The surgical bypass of v. azygos and v. pulmonalis sup. dext. to decompress the
      lesser circulation after extensive resections of the lung is elaborated. The
      operation was performed on 21 patients for cancer of the right lung, and in one
      patient with bilateral disease. The shunting followed pneumonectomy in 11 cases,
      the lower bilobectomy in 7, the upper lobectomy in 2. In 1 patient the operation
      was performed after successive left-sided lower lobectomy and right-sided upper
      lobectomy. The shunting reduced the middle pressure in the lung artery by 13,9
      21,0% of the postresection level. The bypass did not cause statistically
      significant decrease of the oxygenation in the arterialized capillary blood.

PMID- 8753952
TI  - [Initial experience with the surgical treatment of hypertrophic cardiopathy using
      an apico-aortic valved conduit].
AB  - Long-term results (up to 3 years) of operative treatment of first patients with
      complex obstruction of the left ventricle outflow tract (hypertrophic
      cardiomyopathy--10 patients, congenital subaortic tunnel stenosis--1 patient)
      with the help of apico-aortic valved conduit are presented. There was no
      intrahospital lethality. Two patients died in late terms after operation who had
      been operated upon for the III degree of circulation insufficiency. Complications
      associated with using the valved conduit were not noted. All the patients
      operated upon did not need medicamentous therapy (indirect anticoagulants
      excluded), seven of them had the 1st functional class NYHA by the moment of
      examination, two had the 2nd functional class. Continuous observations have
      revealed a marked tendency to normalization of the hemo- and cardiodynamic
      parameters.

PMID- 8753953
TI  - [The surgical procedure in an anomalous muscular bundle of the right ventricle
      combined with an interventricular heart septal defect].
AB  - A defect of the interventricular septum (DIVS) in the perimembranous zone can be
      a source of reversible (hypertrophy) and irreversible (fibrous degeneration)
      alterations of the moderator band (MB), normally or abnormally located in the
      right ventricle of the heart. DIVS goes with changes of MB in 7,27% of the cases.
      Operations are necessary in combinations of DIVS with changes of MB. Surgical
      correction is indicated to patients with DIVS and the abnormal muscular band.
      Operative treatment should not be used for the compensatorily hypertrophic MB,
      located normally or abnormally.

PMID- 8753954
TI  - [The pathogenesis of duodenal stasis].
AB  - The authors consider that the intraduodenal pressure is directly dependent on
      hypertrophy of the muscular layer of the duodenum wall. The formation of the
      duodenal stasis is followed by progressing elevation of the intraduodenal
      pressure, hypertrophy of myocytes, first hypertrophy and then atrophy of nerve
      cells of the ganglionic plexus.

PMID- 8753955
TI  - [The treatment of ulcerative gastrointestinal hemorrhages in the middle-aged and
      elderly].
AB  - Under analysis were results of treatment of 123 patients, 60 years of age and
      older who had ulcerous gastro-intestinal bleedings. Emergency operations were
      performed on 46 patients, postponed operations on 30 patients and there were 47
      planned operations. Out of 38 patients operated upon for resection of the stomach
      5 patients had incompetent sutures of the stomach and duodenum, 4 patients had
      purulent complications, 9 patients died. Out of 11 patients subjected to simple
      suturing of the bleeding ulcer only one endured the operation, 10 patients died
      at the early postoperative period, 3 of them of recurrent bleedings. Vagotomy was
      made in 65 patients, 6 of them died. The amount of complications was minimum.
      Long-term results were followed up in all the alive patients at the period from 1
      to 5 years. After suturing and dissection of the bleeding ulcer in none of 4
      patients were observed good and satisfactory results. After resection of the
      stomach good results were obtained in 8 of 29 patients, satisfactory in 7 and
      unsatisfactory in 14 patients. Good long-term results were noted in all 59
      patients after vagotomy.

PMID- 8753956
TI  - [A rational surgical procedure in diffuse polyposis and multiple primary cancer
      against a background of polyps of the large intestine].
AB  - Under examination there were 292 patients. An analysis of results of treatment
      enabled the authors to conclude that surgical treatment of patients with diffuse
      polyposis of the colon is the method of choice. The method and volume of
      operations must be determined according to the involvement of the colon in
      polyposis, the age and state of the patients. The best method of surgery is a one
      step radical operation-subtotal resection of the colon. Polyps concomitant to
      cancer of the colon should be ablated before the main operation since their
      histological analysis can change the volume of the planned radical operation.
      When choosing the method of surgical intervention for patients with primary
      multiple cancer against the background of polyps the total portion of the colon
      with polyps should be ablated.

PMID- 8753957
TI  - [Carcinoids of the large intestine].
AB  - An analysis of 25 patients with carcinoids of the colon (1,94% of the amount of
      patients with cancer of the colon) was made. In the recent decade this disease
      has become 2 times more frequent. Sixteen patients had carcinoids of the rectum,
      9 patients had carcinoids of the right half of the colon. Malignant carcinoids
      were diagnosed in 16 cases, 8 of them being located in the right half. Radical
      operations are recommended for all carcinoids of the right half of the colon and
      for tumors of the rectum if more than 2 cm.

PMID- 8753959
TI  - [The surgical treatment of severe chronic constipation].
AB  - Materials of surgical treatment of 5 patients are presented who were
      conservatively treated for severe chronic constipation. This treatment was
      unsuccessful. Truncal subdiaphragmatic vagotomy with pyloroplasty was fulfilled
      in 4 patients, in one patient this procedure was accompanied by resection of the
      sigmoid colon. In all the patients the results obtained were promising.

PMID- 8753958
TI  - [The effect of the duration of dynamic intestinal obstruction on the occurrence
      of suppurative complications in acute pancreatitis].
AB  - Longer periods of the dynamic intestinal obstruction in acute pancreatitis are
      responsible for more frequent purulent complications. Laparotomy in acute
      pancreatitis is responsible for a longer duration and greater degree of the
      dynamic intestinal obstruction and more frequent purulent complications. Early
      administration of cooled electrolytic solutions into the jejunum, according to
      the authors' data, reduced the periods of the dynamic intestinal obstruction and
      decreased lethality.

PMID- 8753960
TI  - [The pathogenetic correction of disorders of blood oxygen transport in the
      postshock period of traumatic disease].
AB  - The state of the gas exchange system was analyzed in 79 patients with a severe
      combined trauma (SCT) at the postshock period. It allowed detection of specific
      features of disturbances of the oxygen transport by blood in different kinds of
      injuries. The SCT with a critical injury of the brain is more often accompanied
      by hyperdynamia of circulation within the first two days after trauma, while the
      3rd-4th days are characterized by a sharp drop of the heart index to (2,17 +/-
      0,21) l/min.m2, oxygen transport to (261,9 +/- 37,2) ml/min.m2, oxygen
      consumption to (99,9 +/- 8,3) ml/min.m2. If the SCT was accompanied by a
      contusion of the heart the changes of central hemodynamics were especially
      pronounced and prolonged having a hypocirculatory character with a decreased
      cardiac and stroke index from the first hours of stay at the hospital (20,4 +/-
      1,5) ml/m2 and (2,10 +/- 0,14) ml/min.m2 correspondingly. It led to a substantial
      decrease of indicators of the transport and consumption of oxygen
      correspondingly: (266,5 +/- 25,1) ml/min.m2 and (112,6 +/- 8,2) ml/min.m2. For
      the pathogenetically substantiated therapy of disturbances of the oxygen
      transport by blood the following measures are considered: isovolemic
      hemodilution, moderate sympathetic blockade, the use of membrane stabilizers,
      glucocorticoids, adrenolytics, solcoseryl. The state of the organism system of
      respiration and subsystem of the oxygen transport must be taken into
      consideration when choosing the optimum time for performing the postponed
      operative interventions at the postshock period.

PMID- 8753961
TI  - [The combined treatment of severe craniocerebral trauma taking into account the
      nature of the brain damages and the extent of the hypertensive-dislocation
      syndrome].
AB  - The intracranial pressure was measured in 95 patients with a severe cranio
      cerebral trauma at the postoperative period. Four degrees of the hypertension
      dislocation syndrome were established. The characteristic of operative accesses
      is given. Drainage of the ventricular system of the brain and anterior falxotomy
      were shown to be expedient. The estimation is given to the efficiency of
      dehydration therapy at the early postoperative period against the background of
      intracarotid and intravenous infusions of remedies.

PMID- 8753962
TI  - [Minimal interventions in the surgery of osteochondrosis of the lumbar spine].
AB  - The authors consider that puncture decompression of the intervertebral disc with
      using the endoscopic technique and laser evaporation is a method allowing to
      rapidly and effectively help patients with the root syndrome. All the
      manipulations are made with local anesthesia. The patients started walking on the
      second day after operation.

PMID- 8753963
TI  - [The diagnosis and treatment of chronic osteomyelitis in patients with spinal
      cord trauma].
AB  - Results of examination and treatment of 75 patients with a trauma disease of the
      spinal cord with bedsores are presented. Osteomyelitis which developed in places
      of localization of longstanding bedsores took place in 39% of patients. The
      general complex of treatment included associated intraosseous and direct
      endolymphatic antibiotic therapy as the main treatment as well as the efficient
      preoperative preparation. Good clinical effect was obtained.

PMID- 8753964
TI  - [The possibilities for the surgical treatment of neurogenic fecal incontinence in
      children].
AB  - Treatment of anal incontinence in children with a pathology of the distal portion
      of the spine is a serious problem. We observed 36 children aged from 3 to 6 years
      with the 3rd degree of fecal incontinence. Twenty patients had spina bifida, 12
      had meningocele, 4 children had the following symptoms: disturbed formation of
      the arches, sacrum agenesia, deformity of the distal portion of the spine. The
      conservative treatment was effective but in children without concomitant
      neurological disorders (motor disorders of the lower extremities, disturbance of
      the perineum sensitivity). Great increase of the ano-rectal angle and decreased
      pressure in the anal canal were found in 12 patients with meningocele and in 4
      children with severe defects of the vertebral column. They were subjected to
      operation of free transplantation of the preliminarily denervated muscle by the
      Hakelius method. Good effects were obtained in 10 cases of 12 operations.

PMID- 8753965
TI  - [An intramural hematoma of the duodenum in a child].

PMID- 8753966
TI  - [The blood coagulating activity in burns].
AB  - Data obtained in experiments in 80 rats and in clinical observations of 24
      patients with burns of the II and IIIA degrees showed the activation of vasculo
      thrombocytic and procoagulant links of the hemostasis system with a simultaneous
      depression of the anticoagulative blood system. The thermal trauma is followed by
      a dramatic decrease of the concentration of heparin, fibrinogen, decreased
      activity of antithrombin-III, fibrinolysis and plasminogen activators. There was
      a simultaneous growth of concentration of antiplasmins (alpha 2-macroglobulin and
      alpha 1-antitrypsin).

PMID- 8753967
TI  - [Modezhel' erythrocyte preservative as an experimental and clinical blood
      substitute].
AB  - The model of hemorrhagic shock in dogs was used to show that the infusion of
      "Modegel" normalizes the arterial pressure, substantially increases the minute
      volume of blood circulation. The circulating blood volume rises up to the initial
      level at the expense of the increased plasma volume. "Modegel" gives stable
      correction of the acid-base balance of blood. In clinic "Modegel" was used for
      filling the apparatus of artificial circulation and compared with the blood
      substitute "Gelatinol" for operations on the open heart. Examinations of the
      patients have shown that "Modegel" unlike "Gelatinol" does not induce
      hypercalcemia and hyperosmolarity of plasma while moderate hyperoncoticity of
      plasma is responsible for the circulating blood volume and favorable conditions
      for microcirculation.

PMID- 8753968
TI  - [A trial of using a weak geomagnetic field in treating acute and chronic surgical
      infection].
AB  - Results of treatment of 147 stomatologic and traumatologic patients with acute
      and chronic surgical infection are presented. A weak geomagnetic induction field
      (B approximately 0,125 x 10(-4) T) is a medical factor. Local partial screening
      of the geomagnetic field in the area of the pathological focus shows high
      efficiency of treatment of the patients in question. The nearest positive results
      of treatment equals 99,3%. Long-term positive results--91,9%.

PMID- 8753969
TI  - [Intraportal infusions in the treatment of severely burned patients].
AB  - An experience with treatment of 549 patients (not older than 87 years of age)
      with deep burns of 85% of the body surface has shown high efficiency of the
      regional (selective) intraportal (through the recanalized umbilical vein)
      infusion therapy. It allows elimination of hepatic hypoxia, intoxication,
      microbial aggression etc. This method leads to an improvement of results of the
      treatment and recovery of critical patients who were earlier thought to be
      doomed.

PMID- 8753970
TI  - [The diagnosis and treatment of an epithelial coccygeal cyst complicated by
      fistulae of the gluteal-sacrococcygeal area].

PMID- 8753971
TI  - [The technic of liver resection].
AB  - The use of the method of jet dissection of tissue with the "jet scalpel" in
      resection of the liver for separation of the parenchyma allows to substantially
      decrease the intraoperative blood loss, to visualize the vessels and ducts and
      thus facilitates their ligation which prevents different complications. The
      device developed by the authors for reinfusion of blood is very helpful for
      preventing complications associated with the hemotransfusion therapy.

PMID- 8753972
TI  - [Suture retractors for flap wounds in removing foreign bodies].

PMID- 8753973
TI  - [A combined wound of the esophagus and trachea complicated by mediastinitis and
      massive arrosive hemorrhage].

PMID- 8753974
TI  - [Invasive granulomatous thymoma].

PMID- 8753975
TI  - [2 cases of cholelithic obstruction].

PMID- 8753976
TI  - [The results of the surgical treatment of extensive dermal burns in children].

PMID- 8753977
TI  - [A case of a Barre-Masson tumor].

PMID- 8753978
TI  - [The structure of the transverse fascia and methods for the surgical
      reinforcement of the hernial hiatus in inguinal hernias].

PMID- 8753979
TI  - [The surgical treatment of poorly differentiated lung cancer].

PMID- 8753980
TI  - [Autologous conjunctiva-limbus transplantation in treatment of primary and
      recurrent pterygium].
AB  - The aim of the present study was evaluation of the efficiency of limbal autograft
      transplantation for primary and recurrent pterygia. The results of limbal
      autograft transplantation for advanced and recurrent pterygia are presented for
      58 eyes of 50 patients. The pterygia were primary in 40 eyes and recurrent in 18
      eyes. Free grafts from the superotemporal limbus of the same eye were used to
      cover the exposed sclera. Postoperative followup ranged from 2 to 26 months, with
      a mean of 13 months. The overall recurrence rate was 31% (22.5% in primary
      pterygia and 50% in recurrent pterygia). Recurrence rates were significantly
      higher in patients from southern Europe than in patients from northern Europe.
      Analysis of patients with recurrences (n = 18) revealed severe tear film
      abnormalities in eight cases. Seven patients were found to have transplants of
      insufficient size. Analysis of our results provides evidence that the experience
      of the surgeon is crucial for the success rate of this procedure. Three of six
      surgeons with limited experience had a recurrence rate of 50% or more.
      Additionally, 15 patients who developed recurrent pterygium had returned to
      unfavourable working conditions (e.g. dust, heat). Three of the 18 recurrences
      underwent repeated limbal transplantation and in one of these there was a further
      recurrence.

PMID- 8753981
TI  - [Prospective study of surgical therapy of pterygium: bare sclera technique vs.
      free conjunctiva-limbus transplant].
AB  - Many techniques of pterygium surgery with various rates of recurrence are
      described in the literature. We report on the outcome after pterygium excision
      with bare-sclera technique compared with free transplantation of limbal
      conjunctiva. We used the bare-sclera technique in 21 eyes and performed free
      transplantation of conjunctiva in 34 eyes. The duration of follow-up was 14
      months. In patients operated with the bare-sclera technique there were
      significantly more recurrences (eight vs four, P < 0.025) and cases of
      development of pyogenic granuloma (four eyes vs no eyes, P < 0.01). In patients
      with primary surgery and free limbal transplant we found no case of recurrence,
      but the bare-sclera technique was associated with a recurrence rate of 35.5% (P <
      0.01). We recommend free limbal conjunctival transplantation even in patients
      with primary surgery of a pterygium.

PMID- 8753982
TI  - [Transplant reaction after keratoplasty for keratoconus. Frequency and risk
      factors].
AB  - BACKGROUND: Graft rejection is a leading cause of graft failure in keratoplasty
      for keratoconus. PATIENTS AND METHODS: A consecutive series of 274 keratoplasties
      performed between 1980 and 1991, for keratoconus was studied, some cases
      retrospective and others prospectively with postoperative monitoring up to 1993.
      Excluded from the study were 22 eyes with previous intraocular surgery,
      simultaneous cataract operations, or eccentric grafts. The mean follow-up was
      26.3 months. RESULTS: Endothelial graft rejection was seen in 19 of the 274 eyes
      (6.9%), and in 4 of these eyes (1.4%) the graft failed. After 1 year the
      rejection-free transplant survival rate (Kaplan-Meier survival analysis) was
      93.9% ( +/- 1.5% standard error) and after 4 years, 89.3 +/- 2.9%. Younger age of
      recipient and loosening of the suture were significant risk factors (p < 0.05 for
      each) for graft rejection episodes. Suture loosening was significantly more
      frequent in younger recipients (p < 0.001). Recipient's age was not a risk factor
      in eyes in which suture loosening did not occur. CONCLUSION: Younger patients are
      at greater risk of graft rejection in keratoconus, not only because of their more
      "active" immune system but also because of a higher risk of suture problems. More
      attention must be paid to suture problems, especially in younger patients, to
      decrease the risk of graft rejection in keratoconus patients.

PMID- 8753983
TI  - [Decrease of retinal image contrast after photorefractive keratectomy,
      improvement within the scope of surface restitution].
AB  - Photorefractive keratectomy (PRK) with the ArF excimer lasers in current use
      usually approximates the intended corneal curvature by a mean of a delicate step
      type pattern that is smooth off afterwards by reepithelialization and tear film.
      The present study was based on a model eye with axial myopia of -6 D but
      otherwise the optical and geometric properties of the Gullstrand model eye and
      was designed to investigate to what extent. (1) corneal step patterns can reduce
      retinal image contrast and (2) smoothing effects can restore such a loss.
      METHODS. The corneal surface resulting from PRK in the case of a myopia of -6 D
      (optical zone diameter 6 mm) is calculated for the parameters of the model eye.
      The retinal image contrasts of bar patterns are calculated by PSF (point spread
      function) analysis: varying size of pupil, wavelength, bar width, ablation step
      height and degree of smoothing. RESULTS. Step height influences retinal image
      contrast crucially. With step heights above 0.4 micron a massive loss of retinal
      image contrast must be expected, which can, however, be corrected to a useful
      extent by surface-smoothing effects. CONCLUSION. This study indicates that PRK
      with excimer lasers should be performed with low fluence and correspondingly low
      corneal step heights.

PMID- 8753984
TI  - [Intrastromal keratectomy in high myopia. 1 year results].
AB  - Photorefractive keratectomy (PRK) by excimer laser is now a scientifically
      established treatment method in low and moderate myopia. In high and very high
      myopia, however, the formation of severe corneal haze or scars and a considerable
      regression of refraction remain obstacles to the use of PRK. One approach to
      these two problems is to perform an intrastromal keratectomy. PATIENTS AND
      METHOD. Between September 1992 and September 1994 intrastromal keratectomy was
      carried out in 42 eyes with myopia between -8.625 and -36 D. Twenty-one eyes
      (spherical equivalent of pre-operative refraction between -12.12 and -36 D) were
      treated by keratomileusis in situ, and 21 eyes (spherical equivalent of pre
      operative refraction between -8.625 and -29.25 D) by intrastromal excimer laser
      keratectomy. Thirty-two eyes were followed up for at least 12 months. RESULTS.
      The post-operative refraction (spherical equivalent) ranged between +1.375 D and 
      5.0 D in the keratomileusis in situ group and between +1.5 D and -3.0 D in the
      intrastromal excimer laser keratectomy group. Nearly all patients regained their
      pre-operative visual acuity quickly. In the long-term follow-up (1 year) no
      significant regression of refraction occurred; the pre-operative visual acuity
      was regained in both groups after 1 year. Significant astigmatism was not
      induced. CONCLUSIONS. Intrastromal keratectomy is able to correct even very high
      myopias quite precisely and without regression of the refractive outcome. In
      addition, considerable haze can be avoided. For these reasons, in high and very
      high myopia intrastromal keratectomy seems to be superior to conventional
      anterior photorefractive keratectomy (PRK) by excimer laser.

PMID- 8753985
TI  - [Lamellar keratoplasty with the excimer laser. Initial clinical results].
AB  - If excimer laser techniques are used to prepare the bed of the recipient eye and
      to prepare the donor lenticule diameter and thickness, congruence of the cut
      surfaces will be optimal. MATERIALS AND METHODS. The preliminary in vitro
      investigations have already been reported. We now present the clinical results of
      three patients with circumscript corneal opacities, whom we treated with the
      lamellar keratoplasty in accordance with the calibration method we developed
      (follow-up 4-12 months). The lenticule thickness required varied between 320 and
      415 microns, depending on the extent of the opacity. The lenticule was fixed with
      a suture for 9 months. RESULTS. All transplants healed without complications. The
      parts of the cornea treated with the laser did not show opacities in the
      "interface" or adjacent corneal layers. CONCLUSION. Besides optimal fit of the
      transplant, the absence of intrastromal opacities makes the instrument and
      apparatus requirement worthwhile. The clinical results are superior to those of
      conventional dissection methods. The absence of intrastromal opacities indicates
      that our method will be suitable for treating high-grade myopia. If possible,
      intrastromal treatment should be carried out after lamellation (LASIK).

PMID- 8753986
TI  - [Use of the confocal laser scanning method for determining corneal topography and
      corneal tissue effects in refractive corneal surgery].
AB  - Refraction of the cornea head been generally measured with ophthalmometers or
      computer disk keratometers. We therefore used a confocal laser scanning system
      for measurement of the corneal topography. Enucleated tonicized pig eyes were
      measured before and after laser thermokeratoplasty (LTK). The topographical data
      were used to determine refraction and refractive change; the data were stored
      digitally. The single images and their differences were displayed on a PC. Unlike
      conventional ophthalmometry, confocal laser scanning can demonstrate the
      topographical shape, showing the overall topography of the cornea and local
      corneal effects, e.g., coagulation, mechanical lesions or high-energy laser
      effects. Topographical laser scanning has proven to be a generally useful method
      of determining refraction and surface alterations in corneal refractive surgery.

PMID- 8753987
TI  - [Light scattering study of the cornea in contact lens patients. In vivo studies
      using confocal slit scanning microscopy].
AB  - For the first time, we present measurements of the scattered light intensity of
      the human cornea to determine the functional state of the corneal endothelium. In
      94 contact lens wearers endothelial alterations were measured by means of a newly
      developed confocal slit scanning video microscope and correlated with
      photometrically recorded stromal scattered light intensity. Our control group
      consisted of 26 persons without corneal pathology. It was shown that in persons
      wearing contact lenses the endothelial cell density was significantly below that
      of the control group and endothelial cell polymegatism (coefficient of
      variability of cell size) was significantly greater. Further, in contact lens
      wearers the level of scattered light intensity was significantly higher than in
      the control group, and the difference increased with the wearing time. In
      addition, the variation of the endothelial cell size correlated with the
      increased scattered light within the stroma, only a low correlation was found
      between the endothelial cell density and the scattered light intensity, however.
      From our results it can be assumed that a corneal endothelium with marked
      polymegatism has a reduced hydration function. Thus, decreased endothelial
      function can be determined very early and non-invasively by measuring the corneal
      scattered light intensity. In addition, the scattered light intensity gives
      topographical information about corneal swelling.

PMID- 8753988
TI  - [Imaging (resolution and quantification) of corneal findings with ultrasound
      biomicroscopy].
AB  - Important information on the cornea can be obtained by ultrasound biomicroscopy.
      Intrastromal corneal scars, internal corneal adaptation after penetrating
      injuries or keratoplasties, corneal dystrophies and other lesions can be
      demonstrated. The acoustical examination is in competition with optical methods.
      It has advantages in opaque optical media and in rarely visible regions as well.
      The cornea is characterized acoustically by three highly reflective layers
      (epithelial surface, Bowman's membrane, Descemet's membrane) and two zones that
      are either not very reflective or are only in the middle range (the thin corneal
      epithelium without internal differentiation and the stroma) in which pathological
      structures can be seen.

PMID- 8753990
TI  - [Effect of differentiation on expression of genes for growth factors and growth
      factor receptors in human corneal endothelial cells].
AB  - In earlier publications we described a method for the isolation and long-term
      cultivation of human corneal endothelial cells. In several cultures we observed
      dedifferentiation of these cells, shown by loss of their normal polygonal shape
      and assumption of a fibroblastlike morphology. To reveal the role of growth
      factors for this dedifferentiation we analyzed the expression of genes encoding
      growth factors and growth factor receptors by differentiated and dedifferentiated
      human corneal endothelial cells. By means of northern blot analysis we
      demonstrated expression of the genes encoding basic fibroblast growth factor
      (bFGF), transforming growth factor beta (TGF beta 1), vascular endothelial growth
      factor (VEGF), FGF receptor-1 (flg-type) and epidermal growth factor receptor
      (EGF receptor) by both differentiated and dedifferentiated human corneal
      endothelial cells. In addition, expression of VEGF was stimulated by
      supplementation of growth medium by bFGF. In contrast, expression of the gene
      encoding flt-1, a receptor for VEGF, was only observed in dedifferentiated and
      not in differentiated human corneal endothelial cells. Despite this expression of
      flt-1, the dedifferentiated cells showed no mitogenic response to VEGF. The role
      of growth factors for dedifferentiation of human corneal endothelial cells is
      discussed.

PMID- 8753989
TI  - [HLA typing of donor corneas with extended post mortem time].
AB  - In case of high-risk patients cornea transplantation should be carried out using
      HLA-matched donor corneas to minimize the risk of rejection. HLA typing using
      blood lymphocytes of the donor is impossible because of the long post-mortem
      times. Alternatively, HLA typing can be performed using retinal pigment
      epithelium (RPE). Nevertheless, this method is limited by increasing post-mortem
      times. The aim of the present study was the optimization of culture conditions
      for RPE cells isolated from donor eyes with long post-mortem times. The HLA type
      should be evaluated during an acceptable period of organ preservation of the
      corresponding cornea. In different steps the method for isolation of the cells
      was optimized and a growth medium for RPE cells was established. Various
      supplements, including uvea-conditioned medium, were assessed using growth
      assays. The optimization of culture conditions led to an increase in the
      estimation of the complete HLA I and HLA II antigens from 36% to 74%. The time
      needed for the typing-procedure could be reduced from 38 to 17 days (average). At
      present 30% of the donor tissue with long post-mortem times can be typed in less
      than 14 days.

PMID- 8753991
TI  - [Effect of heparin and ascorbic acid on growth behavior of cultivated corneal
      epithelial cells of the rabbit].
AB  - Although ascorbic acid and heparin are used for local therapy of corneal wounds
      that heal poorly (e.g., after chemical burns), little has been known up to now
      about the mechanisms underlying their effectiveness at the cellular level. The
      aim of the present study was therefore to evaluate the effect of heparin and
      ascorbic acid on the growth behaviour of corneal cells in vitro. For this purpose
      cell cultures from a corneal epithelial cell line were used. Stimulation of the
      cells with heparin at concentrations ranging from 10 to 200 micrograms/ml for 6
      days led to a dose-dependent rise in growth rate (population doublings per day)
      of 0.48 +/- 0.50 to 2.19 +/- 1.65 (mean value +/- standard deviation, n = 10)
      with an EC50 of 132 micrograms/ml. In contrast, the addition of ascorbic acid at
      concentrations ranging from 0.5 to 3.0 mM led on average to a 40% dose-dependent
      inhibition of cell proliferation after 6 days, with an IC50 of 0.7 mM as-corbic
      acid. On the basis of these results, the use of heparin at concentrations of 180
      200 micrograms/ml appears advantageous. In contrast, the local application of
      ascorbic acid for chemical burns with no stromal involvement should be subjected
      to a critical reassessment.

PMID- 8753992
TI  - [Curved lamellar keratotomy for correction of astigmatism. Experimental and
      initial clinical results].
AB  - BACKGROUND: The first experiments for surgical correction of higher astigmatism
      were reported more than 100 years ago. A lot of different procedures were
      strongly recommended at the beginning but then abandoned later on because they
      could not fulfill the expectations regarding the postoperative results and the
      complications. On the other hand, lamellar preparation of the cataract incision
      has been considered a major advance in ophthalmology. The main advantage of this
      incision is that it yields stable postoperative refraction as well as high
      mechanical stability very early (postoperatively). These findings prompted us to
      combine the advantages mentioned above with those of the arcuate transverse
      incision. In this report we present our experimental and clinical results with
      arcuate lamellar keratotomy. MATERIALS AND METHODS: Experiments were carried out
      on 22 cadaver bulbi. The optical zones ranged from 6 to 8 mm and the length of
      the arcuate incisions was between 2 and 7 mm. The clinical data presented here
      were obtained from 20 patients with a 4-week follow-up. These 20 patients had
      undergone cataract surgery previously with an induced astigmatism ranging from
      2.5 to 5 D. Patients were treated with an optical zone of 7 mm or 8 mm. The
      length of the arcuate incision was 3 mm. All incisions were paired. RESULTS: Our
      experiments (cadaver bulbi) showed an approximately linear decrease of the effect
      with increasing width of the optical zone and increasing are length. Our clinical
      results demonstrate that the astigmatism induced by our procedure (including
      potential overcorrection) was 3.41 +/- 1.33 D on the the first day
      postoperatively. All astigmatism was measured with the Zeiss keratometer. After 1
      and 4 weeks the results were 3.98 +/- 1.35 and 3.71 +/- 1.29 D, respectively. The
      induced astigmatism also depended on the width of the optical zone. In the group
      with a 7 mm optical zone the induced astigmatism was 4.5 +/- 1.56 D after 4
      weeks. This effect was remarkably higher than in the 8 mm group with an average
      of 3.35 +/- 0.94 D of induced astigmatism. There were no significant differences
      between visual acuity under glare conditions and the number of endothelial cells
      preoperatively and at 4 weeks follow-up, nor were there variations in refraction,
      depending on the time of day. CONCLUSIONS: Due to the relatively high standard
      deviation of the induced astigmatism we must keep trying to make the results of
      our procedure more predictable.

PMID- 8753993
TI  - [Differentiation of lacrimal gland tumors with high resolution computerized
      tomography in comparison with magnetic resonance tomography].
AB  - In a retrospective study of 15 patients with epithelial and non-epithelial masses
      of the lacrimal gland, the value of high-resolution computed tomography (CT) with
      multiplanar and three-dimensional reconstructions was compared to magnetic
      resonance imaging (MRI). For the differential diagnosis of lacrimal gland lesions
      the following parameters are important: shape of the lacrimal gland, internal
      structure, degree of contrast enhancement and integrity of adjacent bony
      structures. In evaluation of the extent of lacrimal gland lesions, thin-section
      CT with multiplanar and three-dimensional reconstruction is equal to MRI, while
      spiral CT with 1-mm slices is superior to standard CT with 2-mm slices. However,
      internal structure and contrast enhancement of lacrimal glands, integrity of
      adjacent bones and intracranial infiltration are better visualized with MRI than
      with CT. Only inhomogeneous mixed tissue tumors can be differentiated from
      homogeneous tumors by CT due to density differences. In conclusion, MRI is the
      method of choice if lacrimal gland tumors are suspected, while CT is only useful
      in doubtful cases concerning the bony structures as an additional method. Using
      modern imaging modalities, differentiation between epithelial and non-epithelial
      masses is possible for further diagnosis and therapeutic decisions. Both
      pleomorphic adenoma due to its different dense components and malignant masses
      due to bony destruction and intracranial attachment can be differentiated and
      treated in a specific way. Differentiation between non-epithelial masses
      (lymphoma and inflammatory pseudotumor) is only possible with a combination of
      imaging, clinical appearance and in some cases biopsy.

PMID- 8753994
TI  - [Anatomy and pathology of the retrobulbar space in MRI using a high-resolution
      surface coil].
AB  - Because of its high soft tissue resolution and its lack of radiation hazard, MRI
      is considered a valuable method in the diagnosis of orbital disease. Insufficient
      spatial resolution was considered the main drawback of orbital MRI. Another
      problem was the chemical shift artifact caused by shifting of the signal of fat
      and water. To optimize image quality, a high-resolution coil with a small
      diameter was constructed. Twenty patients with intraorbital changes were examined
      with MRI. We used a special surface coil with a diameter of 4 cm. For optimal
      image quality we modified the bandwidth and other parameters of the sequences.
      For comparison additional measurements were performed in 13 patients with the
      standard surface coil (diameter 11 cm) and/or the head coil. The best results
      were obtained with a middle bandwidth (78 Hz); the chemical shift was reduced
      significantly. Little motion artifacts are visible in every examination caused by
      involuntary eye movements, which led to evaluation limitations in 3 cases.
      Compared to the examination with normal coils, the detection of details was much
      better. In 3 cases small changes were only found with the high-resolution orbital
      coil. With the high-resolution surface coil it is possible to examine the orbit.
      It is like looking through a magnifying glass. Using an optimized bandwidth, both
      the signal-to-noise and the chemical shift are acceptable. The new orbital coil
      is especially useful for the detection of small orbital lesions.

PMID- 8753995
TI  - [Age-related macular degeneration. 1. Epidemiology, pathogenesis and differential
      diagnosis].

PMID- 8753996
TI  - [Apoptosis: molecular and cellular mechanisms].

PMID- 8753997
TI  - [Interaction of Oct-proteins with DNA].

PMID- 8753998
TI  - [Phosphorylation of proteins as a factor for regulating viral infection].

PMID- 8753999
TI  - [Expression of human chorionic gonadotropin cDNA in insect cell culture].

PMID- 8754000
TI  - [Expression of the HIV-1 CD4 receptor gene in insect cells using a baculoviral
      system].

PMID- 8754001
TI  - [Determination of the amount of information in nucleotide sequences].

PMID- 8754002
TI  - [A new cosmid vector pDEL-BAC: cloning large fragments of genomic DNA for
      successive introduction of deletions and sequencing the DNA of the resulting
      deletion mutants].

PMID- 8754003
TI  - [Properties of free DNA detected in cell nuclei].

PMID- 8754004
TI  - [Sobemovirus genome from Dactylis glomerata has a luteovirus-like organization of
      the replicase and protease gene modules].

PMID- 8754005
TI  - [Killer genes from the leader region of conjugated plasmid R100 (incFII)].

PMID- 8754006
TI  - [A physical map of Mycoplasma gallisepticum strain A5969 genome and determination
      of its positions on certain genes].

PMID- 8754007
TI  - [Study of the structure-activity organization of the smallpox viral genome. V.
      Sequencing and analysis of the nucleotide sequence of the left terminus of the
      India-1967 strain genome].

PMID- 8754008
TI  - [Functional heterogeneity of p53-responsive elements].

PMID- 8754009
TI  - [Modeling the spatial structure of obelin--a calcium-activated photoprotein from
      the hydroid Obelia longissima].

PMID- 8754010
TI  - [Dynamics of a tryptophan-repressor in solution by nonselective proton
      relaxation].

PMID- 8754011
TI  - [Semi-empiric method of modeling the protein spatial structure using tritium
      planigraphy].

PMID- 8754012
TI  - [Computation of the dispersion of chemical proton shifts in the alpha-CH groups
      in binase].

PMID- 8754013
TI  - [Computation of low-potential proton shifts in the alpha-CH-groups of binase in
      native and compact denatured states].

PMID- 8754014
TI  - [Activity and composition of transcription factor AP-1 in rat embryonal
      fibroblasts transformed by oncogenes E1A plus Ha-ras].

PMID- 8754015
TI  - [Biological activity of recombinant human growth hormone and its analogs].

PMID- 8754016
TI  - [Preparation and properties of hybrid RNAase S', formed by S-protein and S-S
      bound conjugates of (Nle-13,Cys-20)S-peptide with 3'-thiopropyl derivatives
      d(T)15].

PMID- 8754017
TI  - [Production of smallpox proteins, homologous to the human gamma-interferon
      receptor, in E. coli].

PMID- 8754019
TI  - [Antibodies to DNA in immunoglobulin preparations and healthy human blood serum
      are found in free and bound states].

PMID- 8754018
TI  - [Determination of the level of protein contaminants in high-purity DNA
      preparations].

PMID- 8754020
TI  - [Identification and isolation of proteins, recognizing the sequence of the human
      immunodeficiency virus (HIV-1) enhancer].

PMID- 8754021
TI  - [Functional characteristics of liver T-lymphocytes in the allogenic response to
      mutant MHC class I and II molecules].

PMID- 8754022
TI  - [The corticostriatal mechanisms of behavior].
AB  - Experiments in dogs, cats and monkeys revealed that, along with the diffuse
      principle of afferent terminal arrangement within the striatum, there exist some
      features of terminal organisation by the anterior-posterior and medio-lateral
      gradients. The data obtained suggest that the prefrontal cortex and the caudate
      nucleus head maintain programming of intentions and the evaluation of performed
      actions.

PMID- 8754023
TI  - [The neuronal reaction of the rat neocortex to damage to the central
      serotoninergic system].
AB  - Pyramidal neurons of the motor cortex II-III layers developed degenerative
      alterations in response to a selective damage of the rat brain serotoninergic
      system, whereas those of the V-VI layers manifested adaptive changes. The finding
      could be due to a selective sensitivity of the target cells in respect to
      serotonin deficiency.

PMID- 8754024
TI  - [A comparative study of the role of ACTH and beta-endorphin in regulating the
      conditioned-reflex activity of hedgehogs].
AB  - The ACTH was shown to facilitate learning and to enhance the memory processes in
      hedgehogs. Administration of beta-endorphin enhanced the latency of conditioning,
      exert an analgetic effect, reduced the motor and intersignal activities, as well
      as eliminated the inhibitory effects of the limbic cortex stimulation. Different
      influences of the ACTH and beta-endorphin upon the higher nervous activity as
      well as possible mechanisms of these effects, are discussed.

PMID- 8754025
TI  - [The influence of naloxone on the antinociceptive effects of the brain system of
      negative reinforcement in the developing rabbit].
AB  - Participation of opioidergic mechanisms in implementation of inhibitory effects
      of the brain "punishment areas" upon nociceptive afferentation, was studied. The
      antinociceptive effect of electrical stimulation of the "areas" was either
      enhanced or reduced by naloxone depending on the current strength. The role of
      the opioids was shown to diminish with age. The results suggest that the opioids
      are more significant in the realization of the antinociceptive influences woned
      by stimulation of the "brain rewarding" than the "brain punishment areas".

PMID- 8754026
TI  - [The dynamic bioelectrical activity and structural reorganization in different
      parts of the canine brain during the recovery of feeding behavior after
      vagotomy].
AB  - Restoration of regulation of the feeding behaviour after subdiaphragmatic
      vagotomy in dogs occurs despite of the destruction of nervous fibres within the
      nn. vagi and the death of their neurons in medullary nuclei. The finding is
      regarded as a result of formation of a new dominant state in the central nervous
      system.

PMID- 8754027
TI  - [The effect of veratridine on the release of neurotrophic factors in a nerve
      tissue culture].
AB  - A depolarising agent veratridine was shown to affect the level of neurotrophic
      substances in a combined culture of the newborn rats hippocampus and chick embryo
      spinal ganglia: the growth of sprouts of the ganglia's sensitive neurons was
      enhanced. The effect seems to be mediated by the veratridine effect on the
      hippocampal neurons. The role of an increased level of neurotrophic factors in an
      increase of neuronal activity, is discussed.

PMID- 8754028
TI  - [The focal potentials of symmetrical areas in the frog tectum mesencephali].
AB  - Mono- and bifocal visual influences of different modality and biological
      significance were found to cause a functional brain asymmetry in the Rana
      ridibunda. The mechanism is discussed.

PMID- 8754029
TI  - [The cortical regulation of lactogenesis and lactopoiesis].
AB  - The mammary gland secretory activity, blood circulation, respiration, gas-energy
      exchange and feed efficiency were studied in cows of a strong (S) and weak (W)
      types of the nervous system. In the W cows, the lactating dominant was found to
      be weak, their mammary gland's secretory activity increased less obviously and
      was stabilised at a lower level than in the S cows.

PMID- 8754030
TI  - [The synaptic responses of the neurons of the parietal associative cortex in cats
      to stimulation of the nucleus ruber].

PMID- 8754031
TI  - [Spectral and correlational EEG analysis in the wakefulness-sleep cycle of rats
      with a genetic predisposition to audiogenic seizure attacks].
AB  - The EEG recorded in the KM rats hippocampus, caudate nucleus, central medial
      thalamic nucleus, somato-sensory, visual and auditory cortical areas, were
      analysed. No spontaneous epileptiform discharges were found and the alpha-rhythm
      was predominant during paradoxical sleep.

PMID- 8754032
TI  - [The structural component of the vascular adrenoreactivity of the skeletal
      muscles in normo- and hypertensive rats].
AB  - In anesthetized normotensive (WKY) and spontaneously hypertensive (SHR) rats the
      adrenoreactivity in the maximum dilated vessels of hind leg skeletal muscles was
      compared. Adrenoreactivity mentioned above has been registered as an amplitude of
      changes of hydraulic resistance (R), hydrostatic capillary pressure (Pc) and
      capillary filtration coefficient (CFC) to noradrenaline infusion in the vascular
      bed of perfused skeletal muscles. Resistance changes were more considerable in
      experiments on the SHR comparatively to those in the WKY. Changes of CFC as well
      as Pc in both strains were not statistically differed. The data obtained confirm
      Folkow's hypothesis about increased adrenoreactivity of the resistance vessels in
      hypertensive mammals due to structural changes of the vascular bed.

PMID- 8754033
TI  - [The formation of blood system tolerance in rats to the repeated action of a
      stressor stimulus].
AB  - Repeated immobilisation induced a biphasic dynamic of the blood system stress
      sensitivity: first, an increased neutrophilia, lymphocytopenia, bone marrow
      granulocyte depletion and activation of the erythropoiesis; second, a restitution
      of mature granulocyte-monocyte cells number in the bone marrow and accumulation
      of neutrophils in the spleen.

PMID- 8754034
TI  - [The mechanism of the action of low doses of thyroid hormones on the stressor
      induced changes in rat vascular tonus].
AB  - Small doses of thyroidine were found to diminish a 6-hr immobilisation-induced
      decrease of the mean AP and duration of a hypertension response to blockade of NO
      synthasa. The thyroidine seems to act on the system of endothelial nitric oxide
      synthasa.

PMID- 8754035
TI  - [The role of the endothelium in the mechanism of the action of parathyroid
      hormone on the smooth-muscle cells of the portal vein].
AB  - An endothelium-dependent effect of the parathyroid hormone on the vessels was
      revealed. The hormone was shown to exert an opposite effect on the pacemaker
      smooth muscle cell of the V. portalis [correction of cava] in direct action and
      when mediated through endothelium.

PMID- 8754036
TI  - [The prolactin and thyrotropic hormone content of the blood plasma in neostriatal
      dysfunction].
AB  - In patients with parkinsonism, essential tremor, torsion dystonia, choreic
      hyperkinesis and hemiballism, a significant increase in the prolactin and
      thyrotropic hormone was revealed. Possible interrelationship between
      neuroendocrinological and dysfunction of extrapyramidal structures, is discussed.

PMID- 8754037
TI  - [The erythrocyte reaction of the moving blood in mammals to the action of
      permanent and pulsed low-frequency electromagnetic fields].

PMID- 8754038
TI  - [The effect of the intraperitoneal administration of a physiological solution on
      rat behavior in the "open field" test and on the activity of the enzymes
      participating in neuropeptide metabolism].

PMID- 8754039
TI  - [The enhancement of the physiological resistance of the periodontal tissues in
      white rats under the action of biologically active substances from Laminaria].

PMID- 8754040
TI  - [The heat-induced aggregating activity of the normal blood serum and in arterial
      hypertension in man].
AB  - The data obtained suggest considerable qualitative changes occurring in albumins
      in human essential hypertension. A possible involvement of the albumin changes in
      a multifactorial pathogenic pattern of hypertension is assumed.

PMID- 8754041
TI  - [The effect of EDTA on the impulse activity of cold thermoreceptors and
      mechanical cold receptors in rabbits under deep skin cooling].
AB  - The EDTA restored the bioelectrical activity and increased its rate in majority
      of the skin cold thermoreceptors and mechano-cold receptors of the nasolabial
      area after deep cooling of the skin in anesthetised rabbits. The data obtained
      suggest that a decrease in the calcium level in the blood lowers the temperature
      thresholds of the activity of these receptors.

PMID- 8754042
TI  - [The extracardiac regulation of the work of the heart in the American cockroach].
AB  - Some features of extracardiac regulation of the cockroach heart activity have
      been studied. Analysis of electrocardiogram characteristics when cutting and
      irritating the different nervous elements showed that the vegetative
      (stomatogastric) nervous system could evoke the increase of the heartbeat
      amplitude. Both excitatory and inhibiting influences can be sent to the heart by
      segmental nerves, these influences being eliminated by dissociation of
      connections between the head and thoracic ganglia. Possible mechanisms of the
      somatic and vegetative components integration of insect behavioural reactions are
      discussed.

PMID- 8754043
TI  - [The role of low-threshold tactile skin afferents in rats in the receptor
      response to mechanical damaging exposure].
AB  - Receptor units (RUs) of the Wistar rat foot skin only responded to a dynamic
      phase of mechanical adequate and nociceptive stimuli. Most of the low-threshold
      RUs only responded with a single AP. The RUs which developed changes in the
      response latency as well as an increase in the AP amplitude and duration,
      constituted a special group. The mechanism of the skin low-threshold afferents
      participation in perception of both tactile and damaging (nociceptive) stimuli,
      is discussed.

PMID- 8754045
TI  - [The 90th anniversary of the creation by J. Newport Langley of the theory of
      autonomic nervous system structure (historical essay)].

PMID- 8754044
TI  - [A pharmacological analysis of the central control of the preganglionic
      sympathetic neurons during stimulation of the afferent nerve fibers of the
      digestive tract].
AB  - In acute experiments on cats, effect of adrenergic brain neurons on impulse
      activity of preganglionic fibers of the left splanchnic nerve was studied.
      Afferent fibers of nerves innervating the stomach, duodenum, ileum and ileocecal
      angle were electrically stimulated. Phenoxybenzamine, obsidan, amizyl, iprazid,
      nuredal, dalargine, and morphine were used for pharmacological analysis. Nerves,
      stimulation at 20 Hz of different segments of the digestive tract was accompanied
      by different inhibition of preganglionic neurons. Sympathetic-stimulating effects
      were observed more frequently at 5 Hz stimulation. After vagotomy, alpha- and
      beta-adrenoreceptor block, central cholinoreceptor and monoamine oxidase (MAO)
      block, and after dalargine (0.1 and 0.01 mg/kg) nerves stimulation at 20 Hz was
      followed by sympathetic-stimulating effect. A weak regulatory effect of morphine
      (1 and 10 mg/kg) on ileal nerve stimulation effects was shown. It is suggested
      that excitation from afferent neurons of the vagus is transmitted to central
      cholinergic neurons which, in their turn, excite adrenergic neurons of the brain,
      and the latter inhibit impulsation of preganglionic fibers. MAO block increased
      the balance of excitatory effect of serotonin on spinal reflexes. Morphine and
      dalargine intracentrally may block adrenergic and cholinergic transmissions, as
      well as decrease the release of substance P from afferent neurons. Their
      regulatory action is revealed when different frequencies of stimulation are used.

PMID- 8754047
TI  - [The role of preventive medicine in the system of ecological support for the
      Armed Forces].

PMID- 8754046
TI  - [The organization of health and hygiene measures among the troops working in the
      cleanup of the aftermath of the Chernobyl catastrophe in 1986].
AB  - The authors describe the first days of sanitary and hygienic activities
      organization in troops, taking part in elimination of consequences of Chernobyl's
      disaster and tell the history of limiting dose irradiation determination for
      military personal during peacetime.

PMID- 8754048
TI  - [The evaluation of postgraduate education by sociological methods].

PMID- 8754049
TI  - [The methodological bases for teaching disaster medicine in a military medical
      department].

PMID- 8754050
TI  - [The performance of professional oral hygiene measures in a troop unit].

PMID- 8754051
TI  - [The importance of the mental factor in the pathogenesis and clinical picture of
      military surgical trauma].

PMID- 8754052
TI  - [The diagnosis of disorders of heart rhythm and conductivity in patients with
      mitral valve prolapse].

PMID- 8754053
TI  - [The treatment of acute and chronic frontal sinusitis by means of prolonged
      drainage].

PMID- 8754054
TI  - [Determination of the rhesus classification of the blood].
AB  - The article describes the new two-stage method of determining of Rh-factor
      belonging. At the first stage tsoliclon "Anti-D-super" (monoclonic anti-D
      antibody class IgM) was used. At the second stage Rh-factor belonging is
      determined in test-tube, using standard universal reagent for definition Rh
      factor RhO (D). Combination of negative results at the first stage with positive
      ones at the second stage is a sign of partial antigen D, most probably category
      VI. The persons with partial D are qualified as Rh-positive donors and Rh
      negative recipients.

PMID- 8754055
TI  - [The progression of rheumatic heart defects (a review of the literature)].

PMID- 8754056
TI  - [The intravenous laser therapy of circulatory encephalopathy].

PMID- 8754057
TI  - [Experience in using the Optodan laser dental apparatus].

PMID- 8754058
TI  - [The combination of secondary recurrent syphilis and HIV infection].
AB  - HIV infection in connection with other venereal diseases change greatly there
      clinic development. Authors discuss comprehensively the peculiarities of
      infectious process in case of syphilis connection with HIV-infection, and in
      particular face syphilid, which is met little in practice of venereologists.
      Syndrome of aggravating influence of HIV-infection on clinic syphilis development
      is noted. It usually more serious. In given example syphilis was diagnosed only
      two month later after patient had took medical advice.

PMID- 8754059
TI  - [The psychophysiological support of the combat activities of servicemen].

PMID- 8754060
TI  - [The importance of the human factor in the medical support for flight safety].
AB  - The article examines the stages of introduction and practical application of
      personal and human factors methodology in providing of flight safety, and the
      necessity of there unification is substantiated. Using the concrete examples,
      application of human factors methodology in analyzing causes of pilot erroneous
      actions is shown, and re-orientation directions of flight medical supply with
      regard for suggested conceptual approach are also defined. Side by side with
      health preservation and providing of crew efficiency, realization of sanitary,
      hygienic and psychophysiological requirements to conditions and means of
      professional work become tasks of medical supply.

PMID- 8754061
TI  - [The centenary of the Department of Infectious Diseases of the Military Medical
      Academy].

PMID- 8754062
TI  - [The 50th anniversary of the 114th District Military Hospital of the Moscow Air
      Defense District].

PMID- 8754063
TI  - [Defective phages of bacilli: cell parasites or chromosomal components].
AB  - A review of data on defective phages of bacilli is presented. The genetics and
      morphology of this group of phages, the peculiarities of their induction, and
      data of sequence analysis of the segment of the bacterial chromosome in which the
      phage genome is localized are considered. It is concluded that the genome of
      defective phages should probably be considered a part of the bacterial chromosome
      rather than the genome of a parasite virus of the bacteria.

PMID- 8754064
TI  - [Behavior of heterologous recombinant plasmid pCET in cells of Bacillus
      anthracis].
AB  - Recombinant plasmid pCET was constructed in vivo in cells of enteric and hay
      bacillus, on the basis of plasmids pC194, and pBC16. Plasmid pCET inherits marker
      genes of antibiotic resistance from parental plasmids. Anthrax cells were
      transformed by the recombinant plasmid developed. The behavior of this plasmid
      was studied in vegetative Bacillus anthracis cells, which did not pass through
      the sporulation stage and were cultivated at temperatures permissive for the
      replicon of plasmid pE194. Under these conditions, plasmid pCET was shown to
      replicate autonomously, regardless of the host chromosome, and to retain its
      structure, irrespective of the recipient strain. In this case, the phenotype of
      transformants fully corresponded to the genotype of plasmids inherited. Elevation
      of the cultivation temperature of strains Bac, anthracis (pCET) up to 44 degrees
      C led to the elimination of plasmid pCET from cells of anthrax microbe under
      conditions nonselective for plasmid pCET and its integration with the host
      chromosome under selective conditions. The frequency of plasmid pCET integration
      into the chromosome was approximately 10(-1) for all Bac. anthracis strains
      studied. In population of vegetative cells of strains Bac. anthracis (pCET),
      which passed through the sporulation stage under selective for plasmid pCET
      conditions, DNA of plasmid pCET was detected only in the state integrated with
      the chromosome. Irrespective of the reasons leading to the integration of plasmid
      pCET into the Bac. anthracis chromosome, all strains inheriting this DNA within
      their own genome lost the resistance to tetracycline observed in strains with the
      extrachromosomal plasmid location. Genome amplification of plasmid pCET in the
      chromosome of Bac. anthracis was detected.

PMID- 8754065
TI  - [Molecular genetic study of the strain Streptomyces virginiae-- the producer of
      virginiamycin].
AB  - The level and the character of the Streptomyces virginiae virginiamycin-producing
      strain's resistance to self-produced antibiotic and a number of antibiotics from
      different groups were determined. S. virginiae was shown to display constitutive
      and inducible resistance to self-produced antibiotic. The phenomenon of cross
      inducible resistance of the strain to virginiamycin and the antibiotics
      erythromycin, oleandomycin, and thiostrepton was demonstrated. The pTO1 and
      pVGTB24 plasmids were introduced into the strain by the method of intergeneric
      conjugation with Escherichia coli. Site-specific integration of the pTO1 vector
      into the S. virginiae chromosomal attB site without disturbance of growth,
      differentiation, and productivity of the strain was shown. The multicopy
      autonomously replicating plasmids pIJ699, pIJ702, pWOR109, and the integrative
      pZAT22 plasmid were introduced into the strain via electrotransformation of
      germinating spores. The efficiency of transformation was 1-5 x 10(3)
      transformants per 1 microgram DNA. The stable inheritance of the plasmids in S.
      virginiae without structural rearrangements was shown. These results allow the
      use of these plasmids to clone genes into S. virginiae.

PMID- 8754066
TI  - [Phenotypic plasticity of wing size and shape in Drosophila melanogaster and D.
      simulans].
AB  - Variation of 13 morphometric wing characters in relation to temperature of
      development was studied in two sibling species Drosophila melanogaster and D.
      simulans. Three principal components that accounted for 73% of variation of these
      characters were identified. The first component was interpreted as general wing
      size, while the second and third components described wing shape. Temperatures of
      maximal wing size and temperatures corresponding to the highest values of the
      third principal component (proximal-distal ratio) were different in the species
      studied. In each of the species, reaction norm curves of the three-principal
      components were different, indicating qualitative differences between reaction
      norms of characters belonging to the same organ. Variances of both general wing
      size and shape were different at different temperatures. Variance of general wing
      size was lower at intermediate temperatures and higher at high and low
      temperatures. Correlations between wing measurements were significantly different
      at different temperatures.

PMID- 8754067
TI  - [Localization of RecA-like proteins in preparations of spread nuclei of mouse
      spermatocytes at meiotic prophase I].
AB  - Earlier, polyclonal antibodies to Escherichia coli RecA protein were used to
      identify immunologically related proteins in meiotic spermatocytes of different
      eukaryotes. At least one such protein proved to be a component of the
      synaptonemal complex (SC) [1]. Subsequent experiments on localization of RecA
      like antigens in SCs of spermatocytes were performed by indirect
      immunocytochemical methods and electron microscopy, which showed that RecA-like
      protein(s) at early leptotene are largely associated with chromatin. During SC
      formation (at leptotene and zygotene), they are found in both lateral elements
      and the central space of SC. In some cases, RecA-like proteins are associated
      with SC substructures that resemble recombination nodules. When spermatocytes
      enter late diplotene, Rec-A-like proteins cease to be detected in SC structures.

PMID- 8754068
TI  - [Population genetic characteristics of highland and meadow Mari. Genetic
      markers].
AB  - ABO blood groups; serum proteins, including transferring (Tf), group-specific
      component (Gc), proteinase inhibitor (PI), and haptoglobin (Hp); and erythrocytic
      enzymes, including acid phosphatase (ACP1) and phosphoglucomutase (PGM1), were
      studied in two ethnic groups from the Marii EI Republic-Highland and Meadow Mari.
      The size of populations examined were 111 and 140 individuals, respectively. Data
      on frequency distribution of phenotypes and genes are reported, and the two
      populations are compared with respect to allelic frequency. To assess the
      subdivision of the population, GST was used. Its value was 0.0041.

PMID- 8754069
TI  - [Molecular nature of the unstable white-starka allele].
AB  - In 1992, Bashkirov et al. described the case of occurrence in line C(1)RM, yw/0;
      Dp(1; 3) wvco/+ of a unique female with light, uniformly colored eyes. This trait
      was not inherited together with Dp(1; 3) wvco but was linked to the X chromosome.
      We denoted this new allele as white-starka (wstr). It proved to be unstable,
      demonstrating mutational transitions to other allelic states with frequencies of
      10(-3) to 10(-5). Southern blot analysis showed that the wstr mutation was
      induced by an insertion of an unknown sequence with a length approximately
      evaluated by the authors in 1992 as 7 kb. Using a wider spectrum of restriction
      endonucleases and a prolonged gel running, we were able to estimate the size of
      this insertion more precisely. According to our data, in the case of wstr we are
      dealing with an insertion in the locus white of a sequence 15.1 kb long. As seen
      from our restriction map of the allele wstr, this insertion does not resemble
      retroposons with long terminal repeats, but is possibly similar to LINE mobile
      elements of Het-A and TART types, characteristic for heterochromatin.

PMID- 8754070
TI  - [Neurosciences and clinical pathology of the brain (Marat Enokovich Vartanian)].

PMID- 8754071
TI  - [Molecular genetic analysis--a new stage in the study of hereditary diseases of
      the central nervous system].
AB  - Molecular genetics is currently the most powerful tool for studying hereditary
      diseases of the central nervous system: Huntington's disease, dopa-nonresponsive
      dystonia, Friedreich's disease, etc. The review presents the most important
      results obtained in this field by the Department of Neurogenetics, Institute of
      Neurology, in collaboration with several Russian and foreign research institutes.
      The authors were the first to perform a molecular analysis of mutations and
      haplotypes in Huntington's disease, dopa-nonresponsive dystonia, Wilson's disease
      and studied the frequencies of various mutations and main genotype-phenotype
      correlations in the Russian population. The first direct diagnosis of
      Huntington's disease in Russia, as well as indirect diagnosis of Friedreich's
      disease, dopa-nonresponsive dystonia and Wilson's disease have been made. The
      authors began to investigate trinucleotide repeat expansion in dominant
      spinocerebellar ataxias and related disorders. The Department of Neurogenetics
      collected a valuable bank of DNA samples, which is sufficient to perform linkage
      analysis in essential tremor, novel forms of congenital cerebellar atrophy and
      progressive muscular atrophy.

PMID- 8754072
TI  - [Current concepts of anticipation in endogenous psychoses].
AB  - It has been recently discovered that anticipation may correlate with expansion of
      trinucleotide repeats in human genome. Therefore some diseases that show
      anticipation, such as bipolar affective disorders and schizophrenia, deserve to
      be studied. Anticipation used to be considered as a result of the onset age
      hereditability that may be described as a lineal decrease of the age of
      manifestation in the following generation. Positive assortative matings leading
      to genes predisposed to schizophrenia ascertainment as well might be responsible
      for earlier onset and disease severity in descendants (Shakhmatova-Pavlova et
      al., 1979; Trubnikov et al., 1978; Gindilis, 1979). Therefore, clinical genetic
      data are to be used as the basis for anticipation study. To exclude statistical
      artifacts, it seems necessary to study three generations in families and proband
      parent siblings as a control group. The phenomena of anticipation can be regarded
      as a special case when a relationship between clinical and molecular genetic
      traits is found. In a common case, trinucleotide expansion study on the basis of
      vast experimental clinical family material suppose to be sensible to elucidate
      the correlations between the clinical level of disease description and molecular
      genetic characteristics. Another approach to the problem is to ascertain special
      relative groups to compare with. For example, the concordant and discordant
      monozygotic tween pairs study also seems to be promising because the molecular
      genetic characteristic of genome instability may help in the elucidation of
      protection mechanisms that prevent disease manifestations.

PMID- 8754073
TI  - [Protein phosphorylation in the normal nervous system and in Alzheimer's
      disease].
AB  - Protein phosphorylation induced by neurotransmitters, hormones, different growth
      factors, nerve impulse is involved in the regulation of a wide variety of
      physiological processes in the nervous system. The data on abnormal
      phosphorylation/dephosphorylation processes in the brain of patients with
      Alzheimer's disease are considered. In AD there are a few phosphoproteins with
      known function, protein kinases, phosphatases that are altered. The own data on
      the decrease in casein kinase 2 activity, content and altered spectrum of
      substrate proteins in Alzheimer's disease are presented. Drastic reductions in
      zinc- and magnesium-stimulated protein tyrosine activities are also recorded. The
      important role of abnormalities in the phosphorylation/dephosphorylation system
      in the stimulation of pathological processes in Alzheimer's disease is noted.

PMID- 8754074
TI  - [The immune system characteristics during normal aging and in Alzheimer's
      disease].
AB  - The paper presents a review of data available in the literature and the authors'
      own findings on age-related physiology and pathology of the immune system. Almost
      all parameters characterizing the functional activity of the immune system in
      Alzheimer's disease (AD) were demonstrated to significantly differ from those in
      the healthy elderly, The magnitude of immunological changes clearly correlated
      with the severity of dementia in AD patients. A hypothesis of the gradual
      development of immunological changes in an AD patient in relation to his dementia
      formation is given.

PMID- 8754075
TI  - [Brain synaptic plasticity in schizophrenia].
AB  - A qualitative and quantitative electron microscopic study was performed. in some
      postmortem brain structures of the dopaminergic system: the substantia nigra,
      ventral tegmentum area, prefrontal cortex (area 10), anterior cingulate cortex
      (area 24), the head of the caudate nucleus in schizophrenia and age-matched
      controls without mental disorders. The study revealed the heterogeneity of
      ultrastructural changes in synaptic ultrastructure and organization in
      schizophrenia as compared to controls. There was an anomalous sprouting of axons
      and a trend to increase the numerical density of axospinous synapses and to
      decrease axodendritic synapses in the schizophrenic brains due to disontogenesis
      or anomalous synaptic plasticity. No correlations with neuroleptic treatment were
      found. Synaptic plasticity might be involved in the pathophysiology and clinical
      symptoms of schizophrenic patients.

PMID- 8754076
TI  - [A clinico-biological study of the thrombocyte serotonin-transport complex in
      therapeutically resistant patients with endogenous depression undergoing combined
      treatment].
AB  - The platelet parameters of the functional status of the serotonin-reuptake
      complex were studied in drug-resistant depressive patients given various regimens
      of complex therapy or selective serotonin re-uptake inhibitors (fluvoxamine and
      fluoxetine). The most persistent and marked clinical effect was seen in
      electroconvulsive therapy and it was due to the normalization of the serotonin
      reuptake system.

PMID- 8754077
TI  - [The neuroimmune relationships during normal aging and in Alzheimer-type
      dementias].
AB  - Relationships between neurophysiological and immune parameters were studied in
      normal middle-aged and elderly subjects and in patients with dementia of
      Alzheimer's type (DAT). The rate of such interaction was minimal in normal aging,
      in DAT neuroimmune relations increased. The correlation between the immune
      parameters and the characteristics of components of visual evoked potentials and
      auditory brain-stem responses suggests that in the middle-aged healthy subjects,
      a primary role in neuroimmune relations belongs to limbicoreticular structures
      and to the mesencephalon. In normal aging, the influence of limbicoreticular
      structures on immune structures decreases. In DAT, the modulation of immune
      processes by limbicoreticular and thalamocortical structures, as well as the
      pontobulbar part of the brain stem increases. In middle age and in DAT, persons
      with different functional brain asymmetry (as estimated from electrophysiological
      criteria) have different lymphocytic functional activities and rates of
      neuroimmune interactions.

PMID- 8754078
TI  - [The genetic aspects of the neuropsychology of verbal memory in schizophrenia].
AB  - Genetic study methods were used while examining the families with schizophrenic
      patients to study the relationships between computerized tomographic and resting
      ECG parameters with memory for information, which differed in degrees and ways of
      organization. In patients, memory performance was affected both by genotype
      controlled high-frequency alpha-rhythm subranges and by integral delta-rhythm
      values determined by environmental factors. A significant role of the right
      hemisphere was found for all forms of remembering. In a group of relatives,
      predictors of different memory forms differed in frequency and topographic
      characteristics to a greater degree. These predictors mainly included
      neuromorphological parameters and power values of alpha-rhythm ranges. Most
      predictors were under considerable genetic determination.

PMID- 8754079
TI  - [Bispecific monoclonal antibodies: the isolation and study of their antigen
      binding properties].
AB  - Bifunctional antibodies (bABs) having a double specificity to alpha-endorphin
      (alpha-END) and horseradish peroxidase (HRP) were produced by hybridoma
      technology. The antibodies constituted about 28-29% of all immunologically active
      IgG secreted by hybrid hybridoma (quadroma). The quadroma was isolated by fusion
      of two murine hybridomas (anti-HRP and anti-alpha-END) with distinct phenotypes:
      double mutant AMD(R)/NAT(S) and its wild type. To produce the double mutant
      phenotype, an actinomycin D-resistant (AMD(R)) mouse myeloma was used to initiate
      one of the parental hybridomas. bABs were purified from quadroma culture medium
      and ascitic fluids by sequential HRP-sepharose and alpha-END-sepharose affinity
      chromatography. With radioimmunoassay, the affinity of the individual anti-alpha
      END combining sites of bABs was shown to be identical to that of parental
      monoclonal antibodies. Binding to the second antigen (HRP) did not affect the
      binding of bABs to alpha-END. bABs proved to be efficient for the determination
      of endorphins and their precursor proopiomelanocortin in immunohistology and
      immunoblotting.

PMID- 8754081
TI  - [The scientific programs of the Mental Health Unit of the World Health
      Organization].

PMID- 8754080
TI  - [The concepts and conceptual models of psychopharmacology].
AB  - The present approaches to the testing and use of drugs, psychotropic ones in
      particular, are characterized by inadequate efficiency: the ratio of agents
      successfully undergone preclinical, clinical, and postclinical tests is 100:5:1
      and in clinical psychopharmacotherapy, the proportion of drug-resistant patients
      and the incidence of side effects are rather high. The groundless supposition
      that interspecies- and intraspecies-specific sensitivity to drugs is equal may
      explain this notion, which contradicts the concept of the biochemical stability
      of species and to the principle of molecular economy in species-specific ratios.
      To enhance the efficiency of tests and pharmacotherapy, it is suggested that the
      existing conceptual model "concentration-effect" should be replaced by the
      extended one "sensitivity-concentration-effect" as it is more scientifically
      substantiated. Increases in the efficiency of psychopharmacotherapy may be, among
      other things, reached by individually predicting the most effective psychotropic
      agents with clinical, paraclinical, pharmacokinetic, and other predictors.

PMID- 8754083
TI  - [The vital tasks of preventive medicine].
AB  - The article discusses the actual problems of prophylaxis in common system of
      troops medical supply and defines the subsequent reformative ways of preventive
      medicine. First of all, the necessity of organized principles revision of
      prophylactic direction is connected with the fact of main health indices negative
      dynamics of Armed Forces personal, indicative of weakening of all types of
      prophylactic work. These are prophylactic work among recruits during their
      adaptation to military service conditions, prophylactic medical examination,
      tempering, fiscal training and prophylaxis of infectious diseases. However, we
      shouldn't forget about positive experience accumulated in the past, as much as
      possible we should use the achievements of military medical science. For further
      development of preventive direction of troops and fleet medical supply the
      priority ways of essential tasks decision of military medicine have been planned.
      It is necessary to connect the decision of concrete tasks with general
      perspective of introduction in Armed Forces of region system of servicemen
      medical supply.

PMID- 8754082
TI  - [The development of the public health system in Russia and its social essence].

PMID- 8754085
TI  - [The medical examination of citizens who are subject to the military service
      draft].

PMID- 8754084
TI  - [Experience in delivering specialized surgical care in a large hospital].
AB  - Medical troops supply in local armed conflicts demonstrated advantages of fast
      evacuation of wounded personnel by aviation from the seat of combat actions to
      the stage of specialized surgical care. Wounded in head, breast, abdomen
      (particularly in case of multiple and combined character of wounds) are evacuated
      for treatment to central military hospitals equipped with modern diagnostic and
      medical equipment, completed with qualified specialists and having the
      opportunity of prolonged treatment. Surgical care in the zone of combat actions
      is confined to hemostasis, intensive therapy -to supporting of main vital
      functions. The article contains the data about terminations of wounded personnel
      treatment in central military-fleet clinical hospital.

PMID- 8754086
TI  - [The development of specialized sanatorium-health resort treatment].

PMID- 8754087
TI  - [The approach of surgical care to the advanced stages of medical evacuation].

PMID- 8754088
TI  - [A comparative evaluation of soft-tissue wound healing after incision with
      conventional and plasma scalpels].

PMID- 8754089
TI  - [The differential diagnostic characteristics of cardiac-type neurocirculatory
      dystonia in young people].

PMID- 8754090
TI  - [The efficacy of fiber bronchoscopy under outpatient polyclinic conditions].
AB  - Basing on the experience of conducting 795 bronchofibroscopies under conditions
      of polyclinic authors discuss organized and methodological aspects ensuring
      maximal study safety permitting to avoid serious, danger for life complications.
      Pathologic changes of tracheobronchial tree were exposed in 64.6% cases, 46.5% of
      them--inflammations, 4.9% of cases--bronchus cancer. Morphologic cancer
      verification when conducting biopsy was 84.6%, when making cytologic examination
      of bronchial liquid-17.9%.

PMID- 8754091
TI  - [The use of Debridat in treating the irritable bowel syndrome].

PMID- 8754092
TI  - [The epidemiological characteristics of acute intestinal infections in wartime].

PMID- 8754093
TI  - [The psychophysiological support of the professional training of flight personnel
      today].

PMID- 8754094
TI  - [The immortalization of the names of fallen students of the Military Medical
      Academy].

PMID- 8754095
TI  - [The development of specialized medical care for the wounded and ill with
      maxillofacial pathology at the N. N. Burdenko Main Military Clinical Hospital
      during the war and postwar years].

PMID- 8754096
TI  - [The organizational characteristics of the medical support for urban fighting
      (based on the experience of the defensive combat actions in Stalingrad 13
      September-18 November 1942)].

PMID- 8754098
TI  - [Medical technology: the leading trend in the conversion of an enterprise].
AB  - The Izhevsky motozavod (Aksion Public stock company) is one of the Russia's
      largest production associations (PA), which manufactures a wide range of products
      for various purposes, including those for implementation of space programmes.
      Medical engineering is close to space instrument making as it required special
      technologies, high quality and reliability for its manufacture. The development
      and introduction of medical equipment into production of the Izhevsky motozavod
      PA are under way along several basic lines: electrocardiographic equipment and
      defibrillators, devices for maternity and child care, ambulances, reanimobiles,
      etc. The most interesting produce, such as one-channel EK1 TTSSP-01 (for
      emergency care) and EK1T-04 electrocardiographs, DKI-H-04 defibrillator, Oksipuls
      01 pulsoximeter, a DLTB-01 unit for diagnosis and treatment of tubal sterility in
      females, a KPH-01 unit for neonatal resuscitation, an ambulance, a Nadezhda
      reanimobile, etc. are briefly described.

PMID- 8754099
TI  - [Informatics of public health management in the Udmurt Republic].
AB  - The paper outlines the structure and basic directions of activities of the
      Information Computer Center (ICC) of the Ministry of Health in the Republic of
      Udmurt. ICC develops of software for polyclinics, hospitals, counting offices,
      clinical units and other divisions of therapeutical and prophylactic
      institutions.

PMID- 8754100
TI  - [Problems in the planning of medical technology for a cardiological clinic].
AB  - The classification approach gives rise to the necessity of designing new devices
      for cardiological care, which are predetermined where to be used. The criterion
      used for making up a prognostic index is original. The devices have been to be
      promising in clinical practice.

PMID- 8754101
TI  - [Production of medical technology at the Research-Production Center at the
      Izhevsk State Medical Institute].
AB  - Integration of small monodisciplinary enterprises into the association-research
      production center of the medical institute allowed a number of products to be
      designed and manufactured. Among them there is projection microscope, its
      condensers, a blood counter, etc.

PMID- 8754102
TI  - [Perspectives of development and production of portable diagnostic devices for
      therapeutic and cardiological care].
AB  - The paper discusses problems in the development and organization of production of
      inexpensive diagnostic devices designed for use at primary health care services.
      It also provides a programme for developing a family of diagnostic medical
      devices: electron two- and multi-channel medical phonoendoscopes, attachments to
      a portable phonocardiogram-recording electrocardiograph, a portable diagnostic
      apparatus for comprehensive examinations.

PMID- 8754103
TI  - [Computerization of medical technology].
AB  - The object of computerization is practical medical technology which is regarded
      as a complex of methodological and instrumental support for maintaining a
      physician-patient dialogue. The methodological support remain to be a prerogative
      of medicine and, consequently, relatively conservative. The instrumental support
      (as an aid for the methodological one) permits a constant extension of its
      stores. That is why the present paper considers the computerization of medical
      technologies in the context of extension of instrumental support. The replacement
      of paper technology in medicine by computerized one should primarily increase the
      level and quality of obtaining information on the patient and create high
      levelled computerized systems: diagnostic monitoring, reference, expert ones. The
      creation of automatic working places for specialists of therapeutical-and
      prophylactic institutions (TPI), their incorporation into the local computer
      systems of functional departments form an instrumental basis for informatization
      of the whole TPI. A scheme of the computer system of a resuscitation and
      intensive care is given as an example.

PMID- 8754104
TI  - [Problems of medical monitoring of patients and requirements for computer
      monitoring systems].
AB  - Medical monitoring of patients is intended for controlling their physiological
      parameters, providing information to the medical staff as of critical,
      precritical physiological values, as well as for accumulating information on the
      patients' condition in time (trends). The existing monitoring systems require
      further improvement by expanding the types of measuring channels connected to
      them, providing a definite service, adaptability to a concrete medical
      institution. The basic orders to develop and produce such systems were got from
      the leading medical institutions of the Republic of Udmurt. A list of
      physiological parameters requiring monitoring, specifications of transducer
      systems and measuring channels (as a table), as well as demands by for channels,
      as required, records written down into the trend, as results is given. Possible
      variants of the design and use of computer monitors are provided.

PMID- 8754105
TI  - [Development of technical aids in ultrasonic diapeutics and experience in their
      use in public health of Udmurt].
AB  - Analysing the physicians' comments on ultrasonic diagnostic devices revealed it
      necessary to adapt the routine transducers of these devices for diapeutical
      interventions. High-echogenicity needles that direct devices for their
      performance (holders) and special adapters have been designed.

PMID- 8754106
TI  - [A unit for automatic blood cell counting].
AB  - The paper describes and characterizes a Hemoanalysis unit for automatic blood
      counting in the Goryaev chamber, presents an algorithm for automatic counting and
      results of its accuracy and rapidity performance.

PMID- 8754107
TI  - [Automated workplace of the physician-endoscopist as a base for computerization
      of endoscopic studies].
AB  - The paper deals with the complex presentation of data for endoscopic studies on
      personal computers for the benefit of a physician in drawing up medical
      documents, establishing an accurate diagnosis, preparing a treatment regimen, as
      well as in facilitating his work, storing and processing data, searching for
      reference information, drawing up the dynamics of morbidity and its prediction. A
      scheme for complex presentation of the information required for endoscopic
      studies is given.

PMID- 8754108
TI  - [Statistical analysis of medical information on oncologic diseases].
AB  - The paper considers some modes of designing regression and autoregression models
      for predicting morbidity rates, as well as methods for correlation and factorial
      analysis of medical statistics on the basis of the materials available on cancer
      morbidity in Udmurtia.

PMID- 8754109
TI  - [Organizational problems of the production of biological preparations of blood].
AB  - The trend of the incidence of tick-borne encephalitis makes one pay attention to
      the production of blood biological preparations. A detailed programme for
      improving the production process, which is included into the federal and
      republican programmes, is outlined.

PMID- 8754110
TI  - [Use of DTTS-01 unit in the diagnosis and treatment of female tubal sterility and
      UNR-01 unit in neonatal resuscitation in obstetric and gynecologic care].

PMID- 8754111
TI  - [Experience in introducing monitoring computer systems in anesthesiology and
      intensive care units].
AB  - The paper describes the author's experience in practically using a monitoring
      computer system at the Anesthesiology, Resuscitation and Intensive Care Unit,
      Republican Clinical Hospital No.1, in Izhevsky Udmurtia. The system enables
      physicians, primarily anesthesiologists-reanimatologists to automate their work.
      It also allows the problem of routine accounting and report documentation to be
      solved.

PMID- 8754112
TI  - [Non-coherent infrared therapy in inflammatory diseases and facial injuries].
AB  - The paper presents the basic specifications of a UZO laser therapy device which
      has been used to examine the effect of non-coherent infrared radiation on the
      microflora of purulent wounds and the repair of osseous tissue in experimental
      animals. A clinical aspect of the investigations involved the efficiency of laser
      and non-coherent infrared radiation in the treatment of patients with
      inflammatory diseases and injuries of the maxillofacial region. Based on their
      experimental and clinical findings, the authors come to the conclusion that the
      clinically significant characteristic of laser radiation is its monochromatism.

PMID- 8754113
TI  - [Massage devices].
AB  - The Akustmash Research Production Association has developed and manufactured
      novel original massage complexes. The pseudoboiling effect of lots of balls that
      chaotically and intensively move under the elastic membrane has been first used
      in the world. This massage is given the name massage via elastic pseudoboiling
      layer (EPL). Four models of massage complexes are outlined in the paper.

PMID- 8754114
TI  - [Magnetic resonance tomography using the contrast preparation Magnevist].
AB  - The diagnostic possibilities of magnetic resonance tomography (MRT) using the
      contrasting agent magnevist were assessed by the examination of 282 patients with
      diseases of various organs and systems. The findings suggest that the contrasting
      agent magnevist shows its highly diagnostic efficiency particularly in central
      nervous diseases, among them there are tumors, multiple sclerosis, some vascular
      abnormalities and cerebral circulatory disorders. The agent used in MPT is also
      highly effective in identifying diseases of the liver (tumors, cysts), uterine
      (tumors), prostate (tumors). The valuable diagnostic information was obtained
      while detecting skeletal and soft tissue tumors and aseptic necrosis of the head
      of the femur.

PMID- 8754115
TI  - [The use of a Russian software-hardware package for the quantitative analysis of
      coronary angiograms].
AB  - The software and hardware complex developed by the Cardiology Research Center,
      Russian Academy of Medical Sciences, jointly with the Technomash Research
      Production Association on the basis of a IBM 386DX personal computer equipped
      with a VS-100 video controller and a DS P31 VS signal processor board. Testing
      has indicated that it provides a qualitative image and a quantitative analysis
      both of phantoms and real images of coronarograms, but more accurately in the
      analysis of the image obtained from a film projector. Valid results are yielded
      when lenses more than 1 mm in diameter are used. Clinical tests have shown that
      the software and hardware complex may yield a rather qualitative image and
      calculate the required diameter of a vessel, virtually without prolonging the
      time of intervention, which is particularly important while making intervention
      procedures and implementing research programmes.

PMID- 8754116
TI  - [The potentials for using ultrasonic study in cardiological practice].

PMID- 8754117
TI  - [The computed tomographic characteristics of adrenal tumors].
AB  - The clinical materials of 121 patients with volumetric abnormal adrenal
      formations exposed to surgical therapy were retrospectively analysed. The data of
      preoperative CT studies were compared with the results of postoperative
      histological analyses of resected adrenal tumors. The specific features of the CT
      images of adrenal tumors were studied according to their morphological structure
      and hormonal activity. The syndromes of radiation signs which are the most
      characteristic of tumors of various histological structure, which may make a
      differential diagnosis of adrenal tumors from their CT image by taking into
      account clinical and laboratory findings.

PMID- 8754119
TI  - [The radiation and chemoradiation treatments of generalized low-grade non
      Hodgkin's lymphomas. 2. The late results].
AB  - Late outcomes of radiation and chemoradiation treatments and chemotherapy were
      analysed in 255 patients with low-grade generalized non-Hodgkin's lymphomas
      (NHL). In terms of total and relapse-free survival, chemoradiation treatment
      regimen yields the best results, as compared to chemotherapy. There is a general
      trend to improve the late outcomes when each of two components of the
      chemoradiation regimen is intensified. Chemoradiation treatment improves late
      outcomes not only in primary patients, but in patients with relapses after
      radiation or chemical therapy. Complete remissions are one of the most important
      predictors of total and relapse-free survival. There is a small group of patients
      with a diffuse lymphocytic type of NHL (about 10-15%). which is characterized by
      extremely slow disease progression and enlargement of individual lymph organs
      (tonsils, lymph nodes, spleen) in whom long-term total and relapse-free survival
      can be achieved by local radiation therapy.

PMID- 8754118
TI  - [The radiation and chemoradiation treatments of generalized low-grade non
      Hodgkin's lymphomas. 1. The immediate results].
AB  - The remission rates were analysed during radiation and chemoradiation treatments
      and chemotherapy of 255 patients with low-grade generalized non-Hodgkin's
      lymphomas. Complete remission was achieved in 15.3% of patients, partial
      remission was in 82.4%. No effect was seen in 2.3% of patients. The rate of
      complete remissions was 4.2% for radiation treatment, 29.5% for chemoradiation,
      and 10.6% for chemotherapy. Chemoradiation treatment regimen was the most
      effective for this group of patients, in all morphological types and chiefly in
      Stage III. The intensified chemoradiation regimen improves the immediate outcome
      of treatment; a combination of series polychemotherapy with radiation applied to
      all diseased lymphatic collectors in a cumulative radiation dose of 30-40 Gy. The
      effect of the chemoradiation regimen is virtually completely revealed in the
      combination of three series of polychemotherapy and radiation therapy; the
      continued chemotherapy does not increase the rate of complete remissions.

PMID- 8754120
TI  - [Chemoembolization of the hepatic artery in the treatment of primary and
      metastatic liver cancer].
AB  - The results of hepatic arterial chemoembolization (HACE) with the liposoluble
      cytostatic Dioxadet were analysed in 200 patients. HACE was performed for
      palliative therapy for nonresectable liver cancer in 150 patients ans as neo- or
      adjuvant therapy in addition to hepatic resection in 50 patients. The oily
      chemoembolizate was injected into the portal vein along with HACE in 50 patients.
      The results have shown that HACE, particularly in combination with intra-portal
      chemoembolization is an effective palliative treatment for nonresectable
      malignant liver tumors, by increasing survival rates at least in half the
      patients. Pre- and postoperative chemoembolization reduces the number of relapses
      after resection of liver neoplasms.

PMID- 8754121
TI  - [A mathematical analysis of the relationship of the clinical manifestations of
      side effects to the blood biochemical indices in subjects undergoing x-ray
      contrast studies].
AB  - During 73 single contrast investigations with 76% triobrast, 76% verographin, 76%
      urographin, urotrast and omnipaque-300, 65% of patients had clinical adverse
      reactions which were mainly mild. In 79% of cases, the syndrome of side effects
      consisted of one clinical manifestation. The occurrence of clinical adverse
      reactions caused by diatrizoate derivatives was proved to be associated with the
      elevation of blood levels of histamine and prostaglandin F2 alpha, with the
      activation of the complement system by an alternative pathway and to be
      independent of the sex and age of patients. According to the effects of contrast
      media on these blood biochemical parameters, patients are classified as
      "tolerant" and "sensitive", the proportion of the latter is 50-80%. With this,
      plasma histamine levels greater than values of the capacity of the complement
      system to activate by the alternative pathway greater than blood prostaglandin F2
      alpha amounts may serve as mathematically significant criteria for the likelihood
      of side reactions occurring in the contrast diagnosis with diatriazoates. An
      elevated diastolic pressure is a valid symptom of side effects of the radioopaque
      media tested by us on the human body.

PMID- 8754123
TI  - [The methodological problems of ultrasonic study of the adrenals in children].

PMID- 8754122
TI  - [Intraoperative radiation therapy: its technological support, potentials and
      prospects].
AB  - The authors' experience with intraoperative radiotherapy (IORT) in 129 patients
      with a tumorous process at various sites has demonstrated that in most clinical
      events, single radiation doses of 10-20 Gy is insufficient to have a persistent
      local effect and requires additional pre- or postoperative remote irradiation.
      The use of IORT as a single component of radiation exposure does not lead to
      significant radiation damages to normal tissues. When IORT is combined with
      remote irradiation (the latter using doses of 30-60 Gy), 30% of patients develop
      radiation-induced normal tissue lesions. In the context of enhancing the local
      effect and, if possible, decreasing the dose of remote irradiation, it is
      expedient to increase IORT doses, which is in turn fraught with higher incidence
      and severity of radiation lesions. In this connection, it seems urgent to have a
      look for the potentialities to expand the radiotherapeutical range. This follows
      several directions.

PMID- 8754124
TI  - [The ultrasonic diagnosis of stomach cancer].

PMID- 8754127
TI  - [The ultrastructure of the epithelial endocrinocytes of the appendiceal mucosa in
      appendicitis patients].
AB  - The electron microscopic study of the vermiform process epithelium under
      inflammation showed five types of endocrinocytes, based on the ultrastructure of
      secretory granules: EC, DI, L, I, P. The overwhelming majority of endocrinocytes
      form EC-cells. Besides, cells of a "mixed" type, involving exo- and endo
      endocrinic cells, were revealed. Morphologic and functional alteration of the
      human vermiform process epithelium endocrinocytes under inflammation have been
      noticed.

PMID- 8754125
TI  - [Pioneers].

PMID- 8754126
TI  - [Mycoplasma infections as a possible factor in genetic changes in the cells of
      higher eukaryotes].
AB  - Mycoplasmas (class Mollicutes, kingdom Procaryotae) are able to induce large
      scale chromosome rearrangements in the infected cells. Repeated DNA sequences
      including mobile elements (as IS and Tn) turn out to play a considerable part in
      mutation events of mycoplasmas and host cells.

PMID- 8754128
TI  - [A quantitative analysis of the regional organizational characteristics of the
      aortic endotheliocyte layer in normotensive and spontaneously hypertensive rats].
AB  - Using scanning electron microscopy and semiautomatic image analyser, regularities
      and quantitative changes were studied in endotheliocytes in three regions of
      thoracic aorta during ageing of normal and spontaneously hypertensive rats of the
      Kyoto-Wistar line. The data of morphometric analysis and the results of
      simulating endothelial cell monolayer changes, by means of construction of
      polyrow mosaics, suggest that the number of small endotheliocytes of normotensive
      rats in all aorta regions is lowered in the period from 2 to 10 months to
      increase then from 10 to 16 months. The endothelial cell monolayer changes occur
      as follows: the small endotheliocytes appear and then disappear, keeping their
      random distribution in the endothelial layer. Within the same period, in
      spontaneously hypertensive rats, the behavior of the endothelial layer in the
      region of intercostal arteria ostia and on the dorsal surface is similar to that
      in normal rats, being presumably associated with age changes. In hypertensive
      rats, on the ventral surface of the aorta, a relative number of small cells
      increases at the expense of small cell foci formation. Thus, the provided
      evidence points to a heterogeneity of responses of endothelial layers in
      different regions of the aorta on the constant elevation of pressure.

PMID- 8754129
TI  - [The effect of an injection of N-methylformamide into mice on the cell cycle and
      cell morphology of ascitic hepatoma 22A].
AB  - A cell differentiating agent N-methylformamide (MF) was studied for its antitumor
      activity against a murine ascitic hepatoma 22A. After a 48 hour NMF
      administration (i/p) the tumor cell number was monitored; the distribution of
      these cells in the cell cycle was registered by flow cytometry, ultrastructural
      changes were studied by electron microscope. The polar solvent MF inhibited tumor
      growth, reduced mitotic activity, and nuclear/cytoplasmic ratio, led to
      structural complication of endoplasmic reticulum and mitochondria. The analysis
      of these events is suggestive that in consequence of MF effect on tumor cells,
      proportion of G0/G1 and M cells was decreased, while the proportion of S and G2
      cells was increased.

PMID- 8754130
TI  - [The effect of adriamycin and ethidium bromide on the Ca2(+)-dependent K channel
      of human erythrocytes].
AB  - The influence of cytotoxic agents adriamycine (AD) and ethydium bromide (EB) on
      Ca(2+)-dependent K+ channels of erythrocytes was investigated. The incubation of
      erythrocytes with agliconic part of AD (without aminosugar residue) increased
      Ca(2+)-dependent K+ efflux induced by low concentration of propranolol, while EB
      suppressed the activating effect of propranolol. EB, verapamil and
      triphluoroperazine inhibited Ca(2+)-dependent K+ efflux induced by high doses of
      propranolol. The incubation of erythrocytes with AD took off the inhibitory
      action of EB and verapamil but did not influence the blocking effect of
      triphluoroperazine. Both AD and EB did not influence Ca(2+)-dependent K+ channels
      induced by Ca(2+)-ionophore A23187, and Pb(2+)-dependent K+ efflux from
      erythrocytes. It is suggested that opposite effects of AD and EB on Ca(2+)
      dependent K+ channels are due to activation by AD and inhibition by EB of system
      of Ca2+ transport into cells, but not on their action directly on K+ channel.

PMID- 8754131
TI  - [The effect of ultraviolet microbeam irradiation of the centrosome on cellular
      behavior. IV. Synthetic activity, cell spreading and growth with an inactivated
      centrosome].
AB  - One of the spindle poles of mitotic PK cells was irradiated with UV microbeam at
      anaphase. After irradiation, cell division completed with a minor delay and two
      daughter cells were spreading synchronously. Later on, cells with irradiated
      centrosomes slightly shrunk, while their sister cells enlarged normally. Sister
      cells entered S-phase, some of them undergoing mitosis. In the cells with
      irradiated centrosomes the formation of nucleoli was disturbed and numerous
      primary nucleoli remained for 50 h (the maximum time of observation). RNA
      synthesis in the cells with irradiated centrosomes was twice less than in the
      sister cells, with ribosomal RNA synthesis being suppressed predominantly. Cells
      with irradiated centrosomes did not enter S-phase for as long as 24 h. The same
      irradiation of a portion of cytoplasm outside the spindle performed during
      anaphase did not change the pattern behaviour in daughter cell. In is concluded
      that the centrosome regulates progression throughout the cell cycle, and that
      centrosome irradiation induces specific and irreversible damage of interphase
      cells.

PMID- 8754132
TI  - [The karyotypic variability of Chinese hamster CHLV-79 RJK cells characterized by
      multiple drug resistance resulting from the amplification of the mdr gene
      family].
AB  - Variability in karyotype structure of Chinese hamster lung V-79 RJK cells and of
      their six cell sublines, selected for increasing concentrations of ethidium
      bromide (EB), was investigated in addition to the number of mdr gene copies in
      cells, both EB sensitive and resistant. It is shown that EB resistant cells
      exhibit cross-resistance to different drugs resulting from mdr genes
      amplification. Southern DNA blot hybridization has shown that in Vebr-2 cells
      (the 1st step of selection) the number of mdr gene copies increased by 10 times,
      whereas in Vebr-30 cells (the 6th step of selection) the number of mdr gene
      copies remained the same as in Vebr-2 cells. The level of mdr genes expression in
      Vebr-30 cells being higher than in Vebr-2 cells. In Vebr-2 cells, homogeneously
      and differentially stained regions (HSRs) were detected in loci 1p31 and 1q26 of
      chromosome 1 material (markers Z1 and Z6, respectively). On the following
      selection steps (prolonged cultivation or increased drug concentration)
      additional HSRs appeared in chromosome 2 (locus 2qter), in derivatives of
      chromosome 5 (marker Z7, locus Z7pter) and chromosome X (marker Z2, locus
      Z2qter). In the course of prolonged cultivation, chromosome 2 and derivatives of
      chromosomes 1, 2, 5 and X, in which HSRs were found, participated in the
      formation of new markers resulting from deletions, inversions, insertions and
      translocations of the chromosomal material. It is supposed that mdr genes
      amplification in V-79 RJK cells resistant to EB may be regarded as a factor
      inducing subsequent genome destabilization and eventual progressive changes in
      the karyotype structure.

PMID- 8754133
TI  - [Multimodal evoked potentials and central mechanisms of afferentation in
      trigeminal neuralgia].
AB  - Multimodal evoked potentials in patients with trigeminal neuralgia are analyzed
      in the paper. The comprehensive studies of cortical trigeminal somatosensory
      evoked potentials, visual evoked potentials, and brainstem auditory evoked
      potentials have revealed their changes that are indicative of the impaired
      central mechanisms of afferentation in patients with trigeminal abnormality. The
      findings are discussed in the light of the theory of generator mechanisms of
      neuropathological pain syndromes.

PMID- 8754135
TI  - [Changes in electroencephalograms and brain blood filling in guinea pigs in
      experimental bronchospasm].
AB  - Anaphylactic bronchospasm was simulated in 28 guinea-pigs. Central and cerebral
      hemodynamics were studied by rheography and cerebral biological rhythms were
      explored by electroencephalography. It was found that cerebral circulation
      deteriorated, the slow-wave activity of the brain increased in bronchospasm.

PMID- 8754134
TI  - [Interhemispheric asymmetry in unilateral brain damage].
AB  - Hemispheric functional changes and interhemispheric interactions were studied by
      the bioelectrical parameters of asymmetry in the unilateral brain damage. The
      magnitude of interhemispheric asymmetry was found to depend upon the site of
      injury, achieving its maximum at the right-sided localization of a pathological
      process and slightly changing at the left hemispheric tumor site. The application
      of functional tests was accompanied by profound increases in asymmetry as
      compared with the baseline. The findings may be an informative predictive tests
      for the course of an inflammatory process.

PMID- 8754136
TI  - [Changes in myocardial ultrastructure in diphtheria intoxication].
AB  - A drastic discoordination in the left and right ventricular ultrastructures was
      observed 72 hours after diphtheria toxin given to rabbits with experimental
      diphtheria intoxication. This may cause cardiac death in diphtheria intoxication.

PMID- 8754137
TI  - [Comprehensive evaluations of the action of galvanic current dosages used in
      physiotherapy on the intact myocardium in an experiment].
AB  - The most common physiotherapeutically used intensity (2.4 and 8.0 mA) and
      duration (15, 30, and 45 min) of galvanic current were examined for their effects
      on the intact myocardium in laboratory rats. These effects were found to be
      alterative (damaging) and directly proportional to the dosage: the greater the
      current intensity and duration were, the higher myocytic lesion is. However,
      these changes were transient and myocardial microstructural normalization was
      observed 24 hours later.

PMID- 8754138
TI  - [Effect of adaptation to medium altitude (1600 m) on the stability of parameters
      of lipid metabolism of the myocardium during stress].
AB  - The myocardial levels of total lipids and blood free fatty acids were measured in
      rats exposed to emotional pain, hypoxic, norepinephrine-, and rausedil-induced
      stresses. The indices of anti-radical protection and superoxide-inhibitory
      activity of the heart were calculated. Various stresses in early adaptation to
      the mountain climate were found to enhance lipid peroxidation with a lower
      activity of antioxidative enzymes, total lipids, and substantially increased the
      formation of nonesterified fatty acids. As steady-state mountain adaptation
      during 30-40 days made lipid peroxidation return to the baseline, the total
      amount of lipids decreased, and the level of nonesterified fatty acids increased.
      The nonspecific stresses caused by specific stressors both in low- and high-lands
      caused homeostatic changes. The antioxidative enzymes became more resistant to
      stress-induced prooxidants, their activity enhanced, suggesting that anti-radical
      protection is effected under the mountain conditions. The myocardium becomes
      resistant to any stress due to its leading and adaptive accumulation of
      antioxidative enzymes that inhibit the stress-induced enhancement of lipid
      peroxidation.

PMID- 8754140
TI  - [Effect of UV-irradiation of blood on the course of adaptation to conditions of
      hypodynamia].
AB  - The rabbit experiment has studied the impact of ultraviolet (UV) blood
      irradiation on the course of adaptative processes under restrictive stress.
      Thirty-day hypodynamia was demonstrated to result in chronic stress whose
      pathogenetic links are activated neutrophilic leukocytes, developed disseminated
      intravascular coagulation, atherogenic metabolic changes. UV blood irradiation
      enhanced the body's adaptative potentialities under long-term hypodynamia, by
      diminishing restriction-induced stress lesion.

PMID- 8754139
TI  - [Antistressor action of neutrophilokine].
AB  - Neutrophilokine, a latex-activated neutrophilic secretory product, was tested for
      effects on the body's response to immobilization stress. Preadministration of
      neutrophilokine decreased the magnitude of post-stress changes: neutrophilic
      leukocytosis, lymphopenia, and stress-induced ulcerogenesis in the gastric
      mucosa. It is concluded that triple administration of neutrophilokine induces
      adaptation to immobilization stress.

PMID- 8754141
TI  - [Activity of NADP-dependent dehydrogenase of thymocytes and blood lymphocytes
      after irradiation of rabbits in vivo with long-wave laser radiation].
AB  - To study the mechanisms of immunocompetent cells' response to long-wave laser
      radiation in male Chinchilla rabbits after in vivo emission (lambda = 632.8 nm;
      emissive power, 19 mW) for 15 min, lymphocytes and thymocytes were identified in
      the projection areas of the thymus and femur and the levels of NADP-dependent
      dehydrogenases were measured. The changes found in the levels of thymocyte NADP
      dependent dehydrogenases while exposing the rabbits to radiation in the area of
      the femur, as well as the area-related differences in the modulating effects of
      laser radiation on the activity of the lymphocytic enzymes under study indicate
      the mediated cellular metabolic regulation which is likely to be chiefly affected
      by the autonomic nervous system in the first postradiation minutes.

PMID- 8754142
TI  - [Mechanism of the immunomodulating action of extracorporeally essentiale-modified
      syngeneic erythrocytes during strenuous exertion].
AB  - Exercise induces splenocytes to release a factor inhibiting the productive phase
      of immunogenesis that activates the formation of non-T-antigen-dependent and T
      antigen-dependent suppressors. The administration of essential-modified
      erythrocytes to animals performing exercises make splenocytes to release a factor
      stimulating the cooperation of T and B lymphocytes and inhibiting the formation
      of non-T-antigen-specific and T-antigen-specific suppressors. The factor resulted
      from the essential-modified red blood cells depresses the influence of the factor
      released during exercise.

PMID- 8754143
TI  - [Recovery of various parameters of the functional state of the reproductive
      system in thymectomized rats as affected by thymic membrane factor].
AB  - Ten-month-old male rats thymectomized in early post-puberty were ascertained to
      have lower plasma luteinizing and testicular hormones and higher testicular
      steroid dehydrogenase activity. Following 24 hours of administration of a
      thymocyte membrane structural agent, pituitary gonadotropic and gonadal
      androgenic functions became normal. There was no agreement between the hormonal
      parameters and the levels of nucleic acids in the testes and prostate.

PMID- 8754144
TI  - [Effect of oxygen aeroions on hemostasis and development of arteriosclerosis in
      hypodynamia].
AB  - Experiments on 50 rabbits examined the hemostatic effects of negative oxygen
      aeroions (AI). In control experiments, keeping the animals under hypodynamia led
      to 40% animal death, significant aortic atherosclerosis and myocardial
      infarction. The animals developed the thrombohemorrhagic syndrome with
      hypercoagulemia and drastically suppressed blood fibrinolytic activity. Keeping
      the animals in the excess AI-containing premise saved all rabbits' life and
      prevented arteriosclerosis and myocardial infarction. Unlike the controls, these
      animals failed to develop the thrombohemorrhagic syndrome. Clotting time, plasma
      recalcification time, and plasma silicon and kaolin time did not reduce, but
      prolonged. There was no drop in the content of antithrombin III or rise in values
      of paracoagulation tests. It is recommended that Chizhevsky's electroeffluvial
      chandeliers should be used to prevent hemostatic disorders and arteriosclerosis
      in hypodynamia.

PMID- 8754145
TI  - [Coupling of the processes of microcirculation, uptake and transport of oxygen].
AB  - A correlation of the oxygen uptake and transport with photoplethysmography was
      studied in groups of persons with varying sympathetic tone. For this, noninvasive
      oximetry and photoplethysmography were applied. The findings indicated that the
      efficiency of oxygen transport in persons with marked sympathetic tone depended
      on the systolic constituent of a cardiac cycle and on the tone of precapillary
      vessels. The results suggests that the sympathetic nervous systems plays an
      important role in the coupling of microcirculatory processes at different
      hierarchic levels.

PMID- 8754146
TI  - [Role of lipid peroxidation in the mechanism of proliferation of hepatic fibrous
      tissue in experimental chronic hepatitis].
AB  - In chronic hepatitis induced by long-term CCl4 administration to rats, there was
      largely an increase in the formation of malonic dialdehyde and Schiff bases, an
      elevation of glycosaminoglycans and hydroxyproline in collagen fractions, and
      proliferation of hepatic fibrous tissue. Therapy of CCl4-induced hepatitis with
      the hepatoprotective antioxidants essentiale and legalone led to decreases in the
      rate of lipid peroxidation, the production of glycosaminoglycans and collagen and
      to morphological manifestations of hepatic fibrosis. There was a moderate
      correlation between the indices of lipid peroxidation and hepatic fibrosis.

PMID- 8754147
TI  - [Role of free radical oxidation in the pathogenesis of acute hepatic necrosis in
      visceral-ischemic shock].
AB  - The mechanisms responsible for necrotic damage to liver cells at the stages of
      experimental visceral-ischemic shock were studied by computerized morphometric
      techniques for interphasic nuclei of hepatocytes. A number of geometric, optical,
      and textural parameters of the structure of chromatin have been defined, which
      characterize the extent of its damage as shock progresses. The increment of
      degenerative signs of the nuclear structures occurred concurrently with the
      enhancement of free radical processes, which may be indicative of the fact that
      there is their pathophysiological relationship. The findings were comparable with
      those of a multiparametric analysis of chromatin in the isolated hepatocytes
      exposed to free radical oxidation. The coincidence of temporal and structural
      parameters of hepatocytic nuclear alteration in shock and in the model system
      makes the authors conclude that in visceral-ischemic shock a great role in the
      genesis of cytolysis is played by the generation of active oxygen forms and their
      direct or lipid peroxidation-mediated action on the nuclear structures.

PMID- 8754148
TI  - [Role of the antioxidant system in the pathogenesis of toxic hepatitis].
AB  - Four subcutaneous administrations of 2 g/kg of tetrachloromethane to albino rats
      inhibited the hepatic activity of superoxide dismutase, catalase, glutathione
      peroxidase, reduced the concentrations of tocopherol, retinol, ascorbic acid,
      glutathiones, decreased the plasma level of ceruloplasmin and the total
      antioxidative activity of liver tissue. The magnitude of changes in antioxidative
      parameters depended on the severity of hepatocytic destruction.

PMID- 8754149
TI  - [Comparative morphofunctional study of the liver in peritonitis and leg
      gangrene].
AB  - Profound hepatic tissue morphofunctional changes with progressive hepatic failure
      occur in endotoxicosis caused by peritonitis and lower extremity gangrene.
      Comparative quantitative histoenzymatic and biochemical studies have revealed
      hepatic metabolic disturbances in peritonitis and leg gangrene.

PMID- 8754150
TI  - [Status of the pediatric oncohematologic service in Russia].
AB  - In spite of the fact that official statistical data show lower cancer morbidity
      of pediatric population in Russia than in Europe and USA (9.7 against 13.8 and
      13.6, respectively), real cancer incidence may be close to mean incidence in
      Europe and USA as in Moscow it is 14.8 in boys and 12.0 in girls. Lower numbers
      in some other regions may be attributable to low standards of cancer diagnosis
      and inadequate case registration. In Moscow where standards of children's
      hematological service are high the proportion of some malignancies is the
      following: hemoblastoses-48.5%, CNS tumors-19.8%, neuroblastoma-8.0%, renal
      tumors-6.5%, sarcomas of soft tissues and bones-2.4 and 4.6%, respectively. The
      efficacy of anticancer treatment of children in many regions of Russia is poor,
      but the situation may be changed for the best by introduction of new approaches
      developed in the Moscow Research Institute of Pediatric Hematology.

PMID- 8754151
TI  - [Retrospective evaluation of blood immunologic parameters in the course of
      remission of acute lymphoblastic leukemia in children].
AB  - The authors investigated cellular and humoral immunity in 53 children over 3
      years of age suffering from acute lymphoblastic leukemia. The children had
      remission lasting from 6 to 120 months and were followed up for 7-14 years after
      the diagnosis was made. The treatment was performed according to programs of
      polychemotherapy practiced in 1981-1988. In November of 1995 42 children were
      alive, 15 had the disease for 10 years. Lymphocytopenia (absolute number of T
      cells and B-cells fell 3-5 and 2-3-fold, respectively) was reported in all the
      examinees both in early remission and later (6-12, 24-60, 60 and more months
      since the disease onset). In early remission there was a significant reduction in
      the serum IgG, IgA and IgM. In children with ALL lethal outcome serum IgM and
      absolute number of E-RFCa dropped in early remission more significantly
      indicating deep drug-induced depression of lymphocytopoiesis. After 5 years of
      treatment the pool of peripheral T-lymphocytes and T/B lymphocyte proportion
      changed for the best, though their absolute number was subnormal. Serum IgG, IgA
      and circulating immune complexes were 1.3-1.5 times higher than normal which may
      be explained by gastrointestinal pathology and food allergy in the majority of
      children treated.

PMID- 8754152
TI  - [Transcobalamin II levels in blood plasma of children with acute leukemia].
AB  - Transcobalamin II (TcII) level was studied in plasma of 40 children with acute
      leukemia. TcII is a cobalamin-binding protein which mediated the cellular uptake
      of Cbl and interacted with surface membrane receptor of hemopoietic cells. Plasma
      TcII and cobalofilins were analysed by PAGE using 57Co-cyanocobalamin. In
      addition, the mature human placenta with high specificity and affinity to TcII
      receptors was applied for TcII plasma identification. As compared to control,
      significant difference of TcII activity in the plasma of children with ALL was
      noted. There were children with low and high TcII concentration vs. control (484
      +/- 42 and 1166 +/- 62, p > 0.001). Therefore, it is necessary to assay
      individually all the biochemical parameters of Cbl-transport system of children
      with ALL for adequate metabolic correction.

PMID- 8754153
TI  - [Distribution of hematopoietic stem cells in the mononuclear fraction of human
      umbilical cord blood].
AB  - The advances in transplantation of hemopoietic stem cells (HSC) from umbilical
      human blood (UHB) necessitate introduction of effective methods of HSC isolation
      and preservation. The studies show that UHB cells remained viable even after
      several days of storage at room temperature. Density gradients proved effective
      for isolation of cell precursors from UHB. Most of hemopoietic cell-precursors in
      UHB have low density (under 1.070 g/ml) which becomes greater with cell
      maturation.

PMID- 8754154
TI  - [Cell composition of umbilical cord blood in complicated and uncomplicated
      pregnancy].
AB  - Possible influence of most frequently encountered types of pathology during
      pregnancy on the cell composition of umbilical cord blood was studied. These
      pathologies included: treated iron-deficiency anemia, essential hypertension,
      threatening spontaneous abortion. A number and proliferative potential of
      granulocyte-macrophage precursor cells of umbilical cord blood were studied by
      agar drop-liquid media culture method. It was found that the types of pathology
      studied do not influence cell composition, number and proliferative potential of
      granulocyte-macrophage precursor cells from umbilical cord blood. These results
      show that umbilical cord blood after pathological pregnancy can be considered as
      a source of transplantable hemopoietic cells.

PMID- 8754155
TI  - ["Cyclosporin dependence" in the treatment of severe aplastic anemia in
      children].
AB  - Cyclosporin A (CA) was used in the treatment of 2 patients with acquired aplastic
      anemia. Upon reaching hematological remission these children had recurrence
      consequent to dose lowering or discontinuation of CA. The remission occurred
      again when full-dose CA treatment was resumed. Slow 2-year decrease in CA dose
      led to uneventful end of CA treatment without deterioration of blood picture.

PMID- 8754156
TI  - [Subpopulations of peripheral blood neutrophils and lymphocytes in children with
      immune neutropenia].
AB  - Peripheral blood (PB) neutrophils and lymphocytes from 14 patients with immune
      neutropenia were studied using the technique of rosette-formation in 2 neutrophil
      fractions with diverse specific density. All the neutropenia cases were divided
      into 2 groups by phagocytosis completeness in all the PB neutrophil types
      studied. Patients of group 1 had impaired phagocytosis D-RFN in elevated levels
      of these cells, autorosette-forming lymphocytes and neutrophils. Patients of
      group 2 had defective phagocytosis D-RFN and EAC-RFN in combination with
      extremely high contents of autorosette-forming including early lymphocytes. The
      above complex of techniques may be used for prediction of the duration and
      severity of neutropenia which is important for further selective studies into the
      causes of neutropenia and effective treatment.

PMID- 8754157
TI  - [The interaction of peripheral blood leukocytes with alpha1-acid glycoprotein,
      its carbohydrate chains and neoglycoconjugates].
AB  - The interaction of human peripheral blood leukocytes with alpha 1-acid
      glycoprotein (AGP), its glycoforms as well as neoglyco-conjugates representing
      carbohydrate chains of AGP or its fragments was studied by flow cytometry. It was
      shown that the main target cells for AGP as well as for conjugates of its
      carbohydrate chains with polyacrylamide (PAA) are monocytes and polymorphonuclear
      leukocytes but not lymphocytes. The interaction of AGP with monocytes and
      granulocytes are mediated by its carbohydrate chains: the binding of AGP with
      cells was inhibited by AGP, AGP oligosaccharides as well as conjugates of
      oligosaccharides and its fragments with PAA. The data obtained show the existence
      of monocyte (and granulocyte) receptors which interact with complex type
      sialooligosaccharides of AGP.

PMID- 8754158
TI  - [Acute promyelocytic leukemia: model of differential therapy].

PMID- 8754159
TI  - [Alpha-interferon in present-day treatment of myeloma].

PMID- 8754161
TI  - [Updated approaches to erythrocyte and platelet transfusions in children].

PMID- 8754160
TI  - [Importance of automatic blood analysis in clinical practice].

PMID- 8754162
TI  - [Treatment of acute promyelocytic leukemia in children with all-trans-retinoic
      acid].

PMID- 8754163
TI  - [Prolonged artificial ventilation of the lungs in nervous system diseases].
AB  - Artificial ventilation of the lungs (AVL) has been carried out for many years in
      25 patients with nervous diseases. Spontaneous respiration ceased because of
      peripheral neuron involvement in malignant myasthenia (5 cases), chronic
      polyneuropathy (1), paralysis of motor muscles after poliomyelitis (1),
      amyotrophic lateral sclerosis (11), spinopontocerebellar atrophy (1), and because
      of the central neuron involvement in 5 patients, 3 of these with the apnea
      syndrome during sleeping caused by syringobulbomyelia, atrophic process in the
      cerebellum and stem, and Arnold-Chiari's syndrome, and 2 with an extensive
      infarction in the pons (deefferentiation or locked-in syndrome). AVL was the
      longest in patients with paralysis of the motor muscles following acute
      poliomyelitis (23 years) and with amyotrophic lateral sclerosis (about 14 years).
      Prolonged AVL is possible in malignant myasthenia, but it may be discontinued
      during obligatory specific treatment. Specific features of many-year AVL, somatic
      functions and metabolic disorders associated with it are described.

PMID- 8754164
TI  - [Respiratory insufficiency in adults with diphtheric polyneuropathy].
AB  - Twenty-five adult patients with grave diphtheric polyneuropathy after toxic
      diphtheria were followed up. Two symptom complexes of neurologic disorders
      leading to the development of peripheral respiratory failure of different
      severity were distinguished: 1) predominating glossopharyngeal paralysis and 2)
      combination of glossopharyngeal paralysis with grave generalized sensorimotor
      polyneuropathy (with pareses and paralyses of the respiratory muscles). The major
      quantitative parameters of pulmonary functions associated with various
      manifestations of respiratory failure are characterized. The significance of
      information on the type of dysfunction of vocal cords is emphasized. A high
      efficacy of a complex of respiratory reanimation used in the treatment of
      patients with peripheral respiratory failure is demonstrated.

PMID- 8754165
TI  - [Intensive care in myasthenic and cholinergic crises].
AB  - Presents the epidemiology, possible etiology, and pathogenesis of myasthenia,
      methods of diagnosis of the disease, and clinical picture of critical states.
      Describes the present-day methods of treating myasthenic and cholinergic crises:
      programmed plasmapheresis combined with hormone therapy, pulsed therapy with
      superhigh doses of corticosteroids, and the most novel method for the treatment
      of autoimmune diseases, intravenous infusions of immunoglobulins. Draws attention
      to indications for artificial ventilation of the lungs and tracheostomy.
      Enumerates the drugs which are not recommended for patients with myasthenia.
      Emphasizes that the use of the whole complex of modern therapeutic methods for
      the treatment of grave myasthenia helps reduce the mortality to virtually null.

PMID- 8754166
TI  - [Prognostic significance of neurophysiological parameters in nontraumatic apallic
      syndrome].
AB  - The time course of neurophysiological parameters (EEG, evoked potentials of
      various modalities, including P300, and polysomnography) was followed up in 10
      patients with apallic syndrome (AS) of nontraumatic origin (heart arrest, stroke,
      neuroinfection, etc.) during the formation of the syndrome and the condition of
      various severity: incomplete formation of AS eventuating in gross
      psychoneurological defects and complete formation of AS (a stable vegetative
      state). A dynamic follow-up of not only EEG of awaken and sleeping patients, but
      of their evoked potentials, specifically somatosensory and P300, were shown to be
      significant for assessment of the course of AS and prediction of its outcome.

PMID- 8754167
TI  - [Electroneuromyography in patients with severe diphtheric polyneuropathy under
      conditions of artificial ventilation of the lungs].

PMID- 8754168
TI  - [Somatosensory evoked potentials in the evaluation of the effectiveness of
      intensive therapy of ischemic complications in neurosurgical patients].
AB  - Nineteen patients with ischemic disorders of brain circulation were examined. All
      of them were in a critical state and in need of intensive vasoactive therapy.
      Somatosensory evoked potentials (SSEP) were examined in both hemispheres in all
      of them, this being followed by monitoring on the side of the predominant
      involvement. Simultaneously with monitoring, vasoactive therapy was started,
      beginning from rheological agents. Electro-physiologic assessment of the efficacy
      of vasoactive drugs in this group of patients revealed that the time course of
      SSEP helps predict the disease outcome, detect the reaction to a specific
      vasoactive agent, and choose the appropriate scheme of intensive care.

PMID- 8754169
TI  - [Intraoprative identification and monitoring of motor structures of the brain
      stem].
AB  - The purpose of this work was to evaluate the method of identification of motor
      structures of the bottom of the IV ventricle in order to find the zone through
      which it is possible to safely approach the bulky formation and to assess the
      efficacy of subsequent monitoring of these structures for the prevention of their
      intraoperative injury. Fourteen patients with bulky tumors of the caudal portions
      of the brain stem aged 4 to 57 were examined. Motor structures of the brain stem
      (nerves VII or IX, X, and XII, depending on the site of injury) were identified
      by direct electrostimulation of the surface of the rhomboid fossa and recording
      of the motor functions by mechanography of EMG. The results indicate that
      intraoperative identification of motor structures followed by monitoring thereof
      is a useful instrument which helps reduce the surgical risk of injuring these
      structures during surgery on the brain stem.

PMID- 8754170
TI  - [Retraction pressure: a new parameter in intraoperative monitoring of
      neurosurgical patients].
AB  - The injurious effects of self-retained retractors on brain tissue during surgery
      were studied in patients with various neurosurgical diseases of the brain. The
      first part of the study was devoted to retraction pressure in neurosurgical
      patients. The highest values were observed in patients with abnormalities of the
      chiasmal-sellar area, median cranial fossa, and aneurysms of the anterior
      portions of Willis' circle. The second part was devoted to a retrospective
      analysis which revealed a high incidence of complications caused by the use of
      retractors in patients with tumors of the chiasmal-sellar area and median cranial
      fossa. In the third part we assessed the preventive effect of some methods aimed
      at reduction of the brain volume during surgery. Preliminary intravenous infusion
      of mannitol solution, puncture of the tumor cyst, ventricular and, possibly,
      lumbar draining were found to be prophylactically useful. Acute hyperventilation
      and intravenous preinjection of a saluretic were ineffective.

PMID- 8754171
TI  - [Monitoring in surgery of the brain stem].

PMID- 8754172
TI  - [Monitoring of eye movements in surgery of the brain stem and parastem
      structures].
AB  - Intraoperative electrooculograms (EOG) of 44 patients with bulky formations in
      the posterior cranial fossa demonstrated a good correlation of the sum of EOG
      waves caused by mechanical stimulation (aspiration, retraction, etc.) and the sum
      of complexes of EOG waves, on one hand, and the outcome, on other, in patients
      with brain stem involvement and less so in those with involvement of the
      cerebellum. The method is not informative for predicting the status of stem
      structures in surgery on the pontocerebellar angle. Stimulation of cerebral
      tissue caused by electrocoagulation cannot be recognized by EOG because it is
      associated with electric artefacts.

PMID- 8754173
TI  - [Use of propofol (diprivan) for induction of anesthesia in neurosurgical
      patients. I. Pressor reaction to laryngoscopy and intubation of the trachea].
AB  - Pressor reaction to laryngoscopy and intubation of the trachea was studied in 32
      patients with neurosurgical diseases of the brain (supratentorial tumors and
      arterial aneurysms) under conditions of induction anesthesia with propofol
      (diprivan) in the mean dose of 2.85 mg/kg. Diprivan alone did not block the
      development of pronounced pressor reaction to intubation. Combination of diprivan
      in the same dose with dipidolor (0.4 mg/kg) ensured complete blocking of the
      pressor reaction in neurosurgical patients. Combination of diprivan and fentanyl
      (2.85 mg/kg) blocked the development of a pressor reaction not so effectively and
      not in all the examinees.

PMID- 8754174
TI  - [Anesthesiological care in removal of jugular glomus tumor. First experience with
      the use of urapidil].

PMID- 8754175
TI  - [Features of disposition of electrodes in electro-medicamentous anesthesia in
      neurosurgery (a clinical-experimental study)].

PMID- 8754176
TI  - [Use of cerebral oximetry in early diagnosis of cerebral ischemia in
      neurosurgical patients with cerebrovascular diseases].
AB  - Using a new device, INVOS-3100 cerebral oximeter, the rSO2 parameter (oxygen
      saturation of blood hemoglobin in cerebral vessels) was monitored during
      neurosurgical interventions in 84 patients with cerebrovascular diseases
      (arterial aneurysms, arteriovenous malformations, and carotid-cavernous
      anastomoses). Six patients developed grave ischemic complications. In five of
      them the cerebral oximeter showed a more than 5% reduction of the parameter in
      question (by 11%, on an average). The findings permit a conclusion that cerebral
      oximetry is an adequate method of early diagnosis of ischemia in neurosurgical
      patients with cerebrovascular diseases.

PMID- 8754177
TI  - [Changes in indicators of brain metabolism in heart surgery patients under normal
      and hypothermic perfusion].
AB  - Metabolism of the brain was studied in 82 cardiosurgical patients operated on
      under conditions of hypothermal and normothermal artificial circulation (AC). The
      principal differences in the pattern of changes of cerebral metabolism were
      observed at the stage of heart connection to the bloodflow, corresponding to the
      period of warming during hypothermal AC. The detected reduction of oxygen
      extraction and arteriovenous glucose difference in the normothermal group may be
      a result of cerebral bloodflow shunting, and more pronounced stimulation of free
      radical processes be indicative of the possible injury to cerebral structures in
      the absence of protective effect of hypothermia.

PMID- 8754178
TI  - [Water distribution in the brain of dead neurosurgical patients and search for
      clinico-anatomical correlations].

PMID- 8754179
TI  - [Lomir in the treatment of arterial hypertension after angioplastic surgery].
AB  - Isradipine (lomir) is a new highly selective arteriolar vasodilator of the
      dihydropyridine group, characterized by a slight cardiodepressive effect. The
      drug effect on the central hemodynamics and oxygen transport was studied after
      cardiovascular surgery. Arterial pressure and total peripheral vascular
      resistance were reliably reduced at the peak of the drug action, as was the left
      ventricular stroke work and oxygen consumption. A tendency to increase of cardiac
      output and cardiac index was observed. Pulmonary vascular resistance and pressure
      in the pulmonary artery did not reliably change. The drug increased the
      intrapulmonary shunt.

PMID- 8754180
TI  - [Possibilities of hemosorption in intensive care of craniocerebral injuries].

PMID- 8754181
TI  - [Analysis of causes of fatal outcome in children in the intensive care unit after
      removal of craniopharyngiomas].
AB  - Postoperative states of 55 children after removal of craniopharyngiomas are
      analyzed. Clinical and morphological analysis of cases with a complicated course
      of the postoperative period helped single out three groups of patients differing
      by the time of lethal outcome, time course of homeostatic reactions in the
      postoperative period, and autopsy findings. The data will help improve the
      diagnostic and therapeutic methods used in the postoperative period in such
      patients.

PMID- 8754182
TI  - [State of the blood coagulation system in patients after removal of brain
      tumors].

PMID- 8754183
TI  - [Brain death caused by catecholamine crisis during adrenalectomy].

PMID- 8754184
TI  - [A case of fatal outcome due to exceeding the physiological permissibleness of
      surgical manipulations during removal of neurinoma of the 8th nerve].

PMID- 8754185
TI  - [Cerebral protection].
AB  - Sodium influx is the first step in the ischemic cascade. Vornov et al. recently
      demonstrated that reducing ionic flux through voltage-gated Na channels shortens
      the NMDA receptor activity of cultured hippocampal slices in which oxidative
      phosphorylation and glycolysis have been blocked. The implication of this finding
      is that blocking initial events in the ischemic cascade, events which do not
      directly cause neuronal damage, will reduce the damage done by downstream events.
      It also seems intuitively reasonable to suppose that truncating initial steps of
      the ischemic cascade, as distinct from blocking glutamate receptors and
      scavenging free radicals, will reduce the probability of interfering with
      endogenous mechanisms of repair. My guess is that clinically useful, substantive,
      prophylactic, pharmacological cerebral protection will come from drugs that work
      upstream in the ischemic cascade. For pharmacological protection that can only be
      initiated subsequent to an ischemic event, free radical scavengers probably hold
      the most promise for clinical efficacy.

PMID- 8754186
TI  - [Cerebral oximetry].

PMID- 8754187
TI  - [Use of hypothermia in neurosurgery].

PMID- 8754188
TI  - [Plasmapheresis as a method of intensive care in neurology].

PMID- 8754189
TI  - [Advances in the treatment of infiltrating transitional cancer of the bladder].

PMID- 8754190
TI  - [Transurethral thermotherapy with microwaves in patients with benign prostatic
      hypertrophy and urinary retention: comparative study between high energy (25) and
      standard energy (2.0)].
AB  - OBJECTIVES: During a 36-month period, 63 patients with benign prostatic
      hypertrophy (BPH) who presented urinary retention, were treated on an outpatient
      basis by transurethral microwave thermotherapy (TUMT) with the Prostatron device
      using analgosedation. METHODS: Treatment consisted of a single one hour session
      with Prostasoft 2.0 for the first group of 11 patients. The second group of 19
      patients received 2 hours Prostasoft 2.0. The third group comprised of 33
      patients were treated with higher energy TUMT (Prostasoft 2.5/1 h 30 min). The
      number of sessions (144) depended on prostate length: L < 45 mm: one session
      (Prostanec catheter); L < 55 mm: two sessions (additional black catheter
      session); L < 65 mm: three sessions (additional white catheter session). RESULTS:
      In the first group of patients, 54% were catheter-free after one year (5 TURP);
      84% (3 TURP) in the second group; 96% (1 TURP) in the third group. The morbidity
      was similar for all groups. CONCLUSIONS: Only high energy TUMT (Prostasoft 2.5/1
      h 30 min) appears to be a minimally reasonable alternative to surgery in elderly
      patients with urinary retention secondary to prostatism and concomitant diseases.
      Longer followup is warranted to determine if the beneficial effects will persist.

PMID- 8754191
TI  - [Analysis of 34 cases of infiltrating carcinoma of the bladder treated
      exclusively with partial cystectomy (part 1)].
AB  - OBJECTIVES: The widely accepted and, until recently, the only alternative in
      muscle-infiltrating transitional cell carcinoma of the bladder, whatever the
      extent of muscle infiltration, has been radical cystectomy, although the
      advantages of partial cystectomy has not been questioned. METHODS: We reviewed
      the records of 34 patients with infiltrating carcinoma of the bladder stage T2 or
      higher and a follow-up ranging from 3 to 194 months, who underwent partial
      cystectomy. The patient received no radiotherapy and only one patient was treated
      with preoperative chemotherapy. RESULTS: The surgical specimen was tumor free
      (pTO) in 7 patients, pT1 in 7 pts, pT2 in 4 pts, pT3 in 4, pT3b in 8 and Px in 4.
      Six patients showed lymph node involvement. Eleven patients had bladder
      recurrence; 3 had bladder recurrence and metastasis; 1 had bladder recurrence, a
      pelvic mass and metastasis and 2 had metastasis alone. We performed radical
      cystectomy in 2 cases; one for a prostatic cancer and the other for an upper
      urothelial tumor in a solitary kidney. Both bladders were tumor free. The
      extravesical disease free interval and survival were better that those of
      patients submitted to radical cystectomy, although this was a highly selected
      group. CONCLUSIONS: With the same possibilities relative to the extravesical
      disease free interval and survival, this approach requires a shorter operating
      time, carries less risk, low postoperative morbidity and mortality, requires less
      hospitalizations, and has less late sequelae. It affords a better quality of
      life, with no cutaneous stoma, incontinence or impotence. The risk of bladder
      recurrence persists, although the procedures required to resolve the
      complications of bladder diversion or substitution are more aggressive than TUR,
      which is sufficient for most of the recurrences, and if the recurrence is an
      infiltrating tumor, one can always recur to radical cystectomy. This is the
      current situation, even in the era of the so-called "minimally invasive
      techniques". We believe that in this group of patients combination preoperative
      radio- and chemotherapy would have contributed little to the partial cystectomy.
      In our series, it is evident that the pT0 is the result of complete resection by
      TUR. The differences in tumor definition make it very difficult to evaluate the
      benefits of the neoadjuvant measures. Patients with no bladder tumor (pT0) or pT1
      pT2, and even pT3a tumors, should not be included in protocols for evaluating the
      efficacy of combination cystostatic therapy; many of them can be overtreated.
      Preoperative radiotherapy adds nothing with respect to local recurrence of this
      tumor type and it evidently has no effect on metastasis. We should not forget
      that the cytostatic agents currently utilized in combination therapy have severe
      side effects and are therefore only indicated in patients at higher risk of
      distant dissemination at diagnosis. Some studies, however, have indicated that
      the cytostatics may have some negative tumoral effect.

PMID- 8754192
TI  - [Review of 42 cases of penile carcinoma].
AB  - OBJECTIVES: 42 cases of penile carcinoma were retrospectively analyzed to
      determine the overall survival and the influence of treatment and inguinal lymph
      node metastasis on survival. METHODS: The clinical records of 42 patients with
      penile carcinoma that had been treated at our hospital over a 17-year period were
      reviewed, with special reference to the epidemiological aspects, diagnosis,
      staging, treatment and overall survival. RESULTS: The overall 5 and 10-year
      survival were 73% and 43%, respectively. Inguinal dissection was performed in 24%
      of the patients. The overall survival was better in those with no lymph node
      involvement. CONCLUSIONS: Following local surgery of penile cancer, inguinal
      lymphadenectomy of palpable nodes is recommended to improve survival, if
      antibiotic treatment is not effective. Randomized and cooperative studies are
      necessary to assess the efficacy of prophylactic lymph node dissection and its
      influence on survival.

PMID- 8754193
TI  - [Prognosis prediction in patients with transitional cell carcinoma of the urinary
      bladder].
AB  - OBJECTIVES: Many attempts have been made during decades to identify factors
      predictive of prognosis in patients with transitional cell carcinoma (TCC) of the
      bladder. The present study attempts to determine the predictive factors in a
      large series of patients with long follow-up homogeneously treated at three
      institutions from 1983 to 1992. METHODS: The clinical and histological factors
      with presumed prognostic value were retrospectively evaluated in a series of 331
      patients with a mean follow-up of 7.2 years, and a study of survival was
      performed. RESULTS: Univariate analysis showed tumor stage, growth pattern,
      grade, size, coexisting dysplasia, histologic type, topography of the lesion and
      patient age are useful parameters for the prediction of prognosis. The Cox
      analysis revealed tumor stage is the most important prognostic variable (Beta =
      1.23, p < .001), followed by growth pattern as determined by the presence or
      absence of a papillary phenotype (Beta = 1.18, p < .001), tumor size (Beta = .98,
      p < .001), WHO modified histologic grading considering persistence or loss of
      cell polarity (Beta = .73, p < .01), tumor location (Beta = .48, p < .05), and
      histology (presence or absence of phenotypes other than pure TCC, Beta = .45, p <
      .05). Coexisting dysplasia, tumor multiplicity, age and sex did not independently
      influence survival. CONCLUSION: Despite the advancements in the field of
      molecular biology relative to prognostic markers in bladder cancer, the
      conventional morphological parameters and tumor stage continue to be the main
      source of prognostic information in clinical practice.

PMID- 8754195
TI  - [Continuing neurologic assessment in myelodysplasia].
AB  - OBJECTIVES: Myelodysplasia produces a neurological lesion with unpredictable
      urodynamic sequelae. The present study describes our experience in 18 patients
      with myelodysplasia and vesicourethral dysfunction. METHODS: The study comprised
      18 patients (11 males and 7 females) with myelodysplasia and vesicourethral
      dysfunction. Patient median age was 15.7 years (range 7 months-57 years) and the
      mean follow-up was 20 months (range 7-47 months). After physical and neurological
      examination, all patients underwent a complete urodynamic evaluation, including
      selective electromyography of the periurethral sphincter and videocystography.
      The urodynamic studies were repeated regularly during follow-up. RESULTS: 14
      patients (67.7%) showed a lower motor neuron vesicourethral dysfunction; 2
      (11.1%) had upper motor neuron lesion and 2 (11.1%) mixed motor neuron lesion.
      During the study period, no alterations were observed in the urodynamic pattern
      of patients with upper or mixed motor neuron lesions, but 9 patients (64.2%) with
      lower motor neuron lesions showed changes in the urodynamic pattern compared with
      the first evaluation, with alterations in bladder compliance being the most
      frequent. CONCLUSIONS: Alterations in bladder compliance may arise from
      neurogenic and nonneurogenic factors. Our findings indicate the need for close
      urodynamic surveillance of patients with myelodysplasia and vesicourethral
      dysfunction.

PMID- 8754194
TI  - [Performance+ of transrectal ultrasonography in the diagnosis of prostatic cancer
      in patients with abnormal digital examination].
AB  - OBJECTIVES: To determine the incidence of prostatic cancer in patients with
      abnormal digital rectal examination (DRE) and its correlation with PSA levels and
      US findings. METHODS: A retrospective study was conducted on 167 patients with
      abnormal DRE that had been evaluated by PSA, US and prostate biopsy from January,
      1994 to September, 1995. The 95% confidence interval was estimated (C195) for the
      differences observed. RESULTS: Biopsy demonstrated cancer in 73% of the patients;
      67.7% of the patients with DRE classification of T2 versus 88.4% of those with T3
      (C195 = 8%-33.3%); 81.4% of patients with PSA > 10 ng/ml had cancer versus 60.5%
      of patients with PSA > 4 and < 10 ng/ml (CI95 = 3%-37.9%); 79.5% of the cases
      with ultrasound nodes had cancer vs 43.3% of those without (CI95 = 17.3%-55.2%).
      In patients with PSA > 4 and < or = 10 ng/ml, 71% of the cases with ultrasound
      nodes had cancer versus 14.3% with no nodal involvement (CI95 = 26.2%-87.1%). In
      patients with PSA > 10 ng/ml, 83.2% of the patients with ultrasound evidence of
      node involvement had cancer versus 70.6% of the patients with no node involvement
      (CI95 = -10.3%-35.4%). CONCLUSIONS: The incidence of prostatic cancer in patients
      with abnormal DRE was 73%; 81.4% of patients with PSA > 10 ng/ml and 79.5% of
      patients with ultrasound evidence of node involvement and 83.2% of those with
      both of the foregoing characteristics. Biopsy of both prostatic lobes should be
      performed routinely in all patients with abnormal DRE.

PMID- 8754196
TI  - [Usefulness of DURR (dynamic urethral resistance factor) in the study of
      prostatism].
AB  - OBJECTIVES: To determine the utility of the DURR (dynamic urethral resistance
      factor) in the evaluation of prostatism. METHODS: 248 patients with prostatism
      were evaluated by the detrusor pressure-flow rate test, perineal and periurethral
      EMG and voiding videocystography. The Audit software program was utilized to
      process the data from the pressure-flow studies to obtain the parameters for
      urethral resistance (PURR), bladder contractibility (Wmax) and DURR. RESULTS: The
      presence of DURR correlated significantly with abdominal voiding pressure and
      voluntary voiding, and constrictive obstruction, although a higher incidence of
      stenosis in patients with a positive DURR was not demonstrable on
      videocystography. No correlation was observed between EMG activity and a positive
      DURR. CONCLUSIONS: A positive DURR indicates the effect of active urethral
      resistance changes on the voiding dynamics. These active changes can be caused by
      contraction of the periurethral muscles (EMG activity), although not all of the
      cases showing EMG activity have a positive DURR. Furthermore, in some DURR
      positive cases, the EMG is silent, indicating that the urethral smooth muscles
      are involved in the active changes of urethral resistance. The DURR data do not
      always coincide with the perineal EMG findings and therefore do not supplant each
      other.

PMID- 8754197
TI  - [Extracorporeal shock wave lithotripsy (ESWL) in children: our experience in
      1995].
AB  - OBJECTIVES: The present study reviews our experience and analyzes the results
      achieved with extracorporeal shock wave lithotripsy in the treatment of urinary
      calculi in children. METHODS: From 1985 to 1995, 36 children, with ages ranging
      from 5 months to 14 years, were treated by ESWL, and in some cases by combination
      therapy (percutaneous nepholithectomy and/or ureteroscopy). RESULTS: Excellent
      results were achieved in 74.9% of the patients; of these, 52.7% were stone-free 2
      to 90 days after treatment. CONCLUSIONS: Extracorporeal shock wave lithotripsy is
      the treatment of choice in children with urinary lithiasis, although there are
      some exceptions. The method of evaluation and treatment in children are the same
      as in the adult patients.

PMID- 8754198
TI  - [Endourethral prosthesis in recurrent urethral stenosis. Long-term follow-up].
AB  - OBJECTIVES: To describe our experience with urethral stents in the treatment of
      recurrent strictures. METHODS: From March 1991 to July 1992, 17 Wallstent and 1
      Strecker self-expandable stents were implanted. Patient follow-up ranged from 11
      to 40 months. The results were analyzed on the basis of the clinical, urodynamic,
      radiological and cystoscopic findings. RESULTS: Of the 18 patients in whom a
      urethral stent had been implanted, 2 (11.1%) required removal of the stent, 1
      patient was lost to follow-up, 2 had died during follow-up from causes unrelated
      with the procedure. At 40 months follow-up, late complications were observed in 8
      patients (47%): intraprosthetic excrescence, erectile disorders, pollakiuria,
      lithiasis, episodes of RAO, or incontinence. CONCLUSIONS: In our view, the
      implanted urethral stent is a valid alternative when other techniques are not
      feasible or have failed (dilatation, internal urethrotomy, urethroplasty...), but
      we should not forget the long-term complications.

PMID- 8754199
TI  - [New compound needle for percutaneous renal puncture].
AB  - OBJECTIVE: We have developed a needle for direct percutaneous access in order to
      introduce the flexible wire with a single puncture, without creating two parallel
      tracks, thereby affording a lower morbidity than the conventional technique.
      METHOD: The needle consists of an internal and an external device, with different
      lengths and diameters, that let us first create the access to the urinary tract
      with the inner device and then dilate with the outer device in order to introduce
      the metallic wire with a single puncture, sliding the outer over the inner
      device. RESULTS: We can achieve the same number of percutaneous accesses with
      less morbidity since less punctures are required to create the track. CONCLUSION:
      This is a useful needle for any type percutaneous access.

PMID- 8754200
TI  - [Uses of endoscopic video-camera in open surgery].
AB  - OBJECTIVES: To describe a method to obtain images of open surgery at the lowest
      possible cost. The images provide useful information for patient records and
      teaching. METHODS: We have utilized a submersible endoscopic camera with no
      special features, close up lenses or automatic focussing device and a color
      printer. RESULTS: The quality of the images are similar to those obtained with a
      more sophisticated video camera. The pictures were processed with a video
      printer. CONCLUSIONS: We believe that using the endoscopic camera in open surgery
      is a low-cost alternative to the more sophisticated video camera systems.

PMID- 8754201
TI  - The Dornier-Lithotripter U30. First clinical experience.
AB  - OBJECTIVE: It can be claimed that ESWL is an optimal alternative for ablation of
      calculi by external shock waves. The new developments in ESWL have focussed more
      on the economic aspects of treatment rather than enhancing its efficacy or
      reducing the side effects. Since August 1993, the prototype of the Dornier
      Lithotripter U-30 was used at the Department of Urology of the Katharinen
      hospital in Stuttgart. METHODS/RESULTS: In 16 months, 1092 stones were treated
      requiring 1533 sessions. Complete disintegration was achieved in 84%; after 3
      months' follow-up, 85.5% of the patients were stone free. CONCLUSION: The Dornier
      Lithotripter U-30 provides easy handling and a short learning curve and a
      sufficient disintegration of the stones. The device is suitable for safe and
      effective treatment of all urinary calculi, with special respect to in situ
      treatment of ureteral stones.

PMID- 8754202
TI  - Endogenous sodium pump inhibition: current status and therapeutic opportunities.
AB  - One might ask, given the number of false trails that have been pursued, why we,
      and so many others, have continued to pursue the elusive digitalis-like factor?
      The answer can be found in the many review articles cited above [4-13]. In animal
      models of volume-dependent hypertension, evidence favoring sodium pump inhibition
      as at least a contributing factor, is essentially overwhelming. These
      observations are supported by multiple lines of less direct evidence in humans
      which are also compatible with a contribution of a circulating sodium pump
      inhibitor. Indeed, if multiple premature claims announcing the isolation of the
      digitalis-like factor had not appeared, this would be one of a large number of
      interesting scientific areas in which identification of a responsible vector was
      expected momentarily. The disenchantment so often expressed, we believe, reflects
      a response to those premature claims. We echo a recent review on the digoxin-like
      sodium pump inhibitor story from one of the productive groups in this area. "Now
      that there is little doubt that endogenous digoxin-like inhibitors of sodium
      transport exist..., the link between these substances, salt intake and vascular
      tone must be pursued with increasing vigor" [12]. That pursuit, of course, will
      be easier if the criteria concerning the responsible mediator are employed
      systematically. Because the current situation resembles so strikingly the
      situation late in the nineteenth century--when efforts focused on the attempt to
      identify a specific microorganism as the agent responsible for specific disease-
      we employed Koch's Postulates as the organizing principle. The challenge faced by
      Robert Koch over a century ago is identical to the challenge that those of us who
      are interested in digitalis-like factors face today. Passionate advocacy and
      equally impassioned denial can be seen as a stage in the scientific process when
      the problem is important and has proven to be more intractable than anticipated.
      Substantial, but still circumstantial evidence supports strongly a role for a
      circulating digitalis-like factor not only in normal sodium homeostasis and in
      the pathogenesis of salt-sensitive hypertension, but also in the pathogenesis of
      a wide array of processes that have an uncertain etiology. Although supported by
      many lines of evidence, this intriguing concept remains controversial, in large
      part because the responsible factor has proven to be very elusive. Informed
      opinion today ranges from arguments that the agent does not exist to contrary
      arguments that the agent has been identified. A very large number of candidates
      from a wide range of chemical classes have been proposed. Indeed, the large
      number of candidates, none supported by absolutely definitive evidence, has
      contributed to the controversy. In this essay, we have attempted to define and
      illustrate the information that will be required before a candidate becomes
      widely accepted.

PMID- 8754203
TI  - Neurotransmitters involved in the central regulation of the cardiovascular
      system.

PMID- 8754204
TI  - Development of novel anti-inflammatory agents: a pharmacologic perspective on
      leukotrienes and their receptors.

PMID- 8754205
TI  - Drugs affecting plasma fibrinogen levels. Implications for new antithrombotic
      strategies.
AB  - Current evidence indicates that plasma fibrinogen is synthesized by the liver;
      that genetic and environmental factors regulate plasma fibrinogen levels; that
      interleukin-6 (IL-6) affects the synthesis of plasma fibrinogen by mechanisms
      involving protein kinase C, and that during the acute-phase response, monocytes
      generate a variety of monokines including IL-6. Certain drugs and nutrients have
      been reported to lower plasma fibrinogen levels. The mechanism(s) involved in
      this effect is poorly understood. However, since most of these substances
      quantitatively and/or qualitatively affect monocytes, the possibility that these
      drugs affect plasma fibrinogen levels via these cells should be considered. In
      addition to fibrinogen, IL-6 also regulates the synthesis of other acute-phase
      proteins. Especially when combined, major risk factors for atherosclerosis cause
      vascular injury that triggers inflammatory events. This raises the issue of
      whether high plasma fibrinogen levels are just the epiphenomenon of as yet
      unknown events in thrombosis and atherosclerosis. Thus, the issue to be addressed
      is whether high plasma fibrinogen concentrations should be lowered or should they
      serve to suggest strong interventions on established risk factors. As for other
      risk factors, fibrinogen measurements in population-based studies, in parallel
      with measurements of established risk factors will help define appropriate
      directions to be followed to gain insight into the issue and define new
      antithrombotic strategies.

PMID- 8754206
TI  - Aminoglycosides and polyamines: targets and effects in the mammalian organism of
      two important groups of natural aliphatic polycations.

PMID- 8754207
TI  - Recent developments in antidepressant agents.

PMID- 8754208
TI  - Immunopharmacological and biochemical bases of Chinese herbal medicine.

PMID- 8754209
TI  - Molecular biology and evolution of resistance of toxicants.
AB  - To the prevailing biochemical/physiological classification of mechanisms of
      organismal resistance to toxicants, an additional molecular dimension is
      proposed. Predictions are developed regarding the relative prevalence of
      different classes of mutations and are found to compare favorably with reports
      from the literature. In particular, point mutations in target loci were the
      dominant form of resistance for both lab and field selection. Amplifications of
      target loci were less common than structural mutations, and more common for lab
      selected than for field-selected strains. Amplification was the most common
      mechanism of up-regulation of metabolizing enzymes. In comparison, only one
      mutation involving cis-regulation and several involving trans-acting regulation
      were found. Mutations involving gene disruption and down-regulation were
      uncommon, but were found in appropriate cases, i.e., when toxicants stimulated
      rather than inhibited target function and when metabolizing enzymes converted
      toxicants into more toxic metabolites. Additional phenomena of likely but
      uncertain importance are genetic "succession," recombinational limitation, and
      negative cross-resistance. More work on these phenomena and on quantification of
      fitness costs of resistance is recommended.

PMID- 8754210
TI  - Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from
      Drosophila, mice, and humans.
AB  - Recent studies of mitochondrial DNA (mtDNA) variation in mammals and Drosophila
      have shown an excess of amino acid variation within species (replacement
      polymorphism) relative to the number of silent and replacement differences fixed
      between species. To examine further this pattern of nonneutral mtDNA evolution,
      we present sequence data for the ND3 and ND5 genes from 59 lines of Drosophila
      melanogaster and 29 lines of D. simulans. Of interest are the frequency spectra
      of silent and replacement polymorphisms, and potential variation among genes and
      taxa in the departures from neutral expectations. The Drosophila ND3 and ND5 data
      show no significant excess of replacement polymorphism using the McDonald
      Kreitman test. These data are in contrast to significant departures from
      neutrality for the ND3 gene in mammals and other genes in Drosophila mtDNA
      (cytochrome b and ATPase 6). Pooled across genes, however, both Drosophila and
      human mtDNA show very significant excesses of amino acid polymorphism. Silent
      polymorphisms at ND5 show a significantly higher variance in frequency than
      replacement polymorphisms, and the latter show a significant skew toward low
      frequencies (Tajima's D = -1.954). These patterns are interpreted in light of the
      nearly neutral theory where mildly deleterious amino acid haplotypes are observed
      as ephemeral variants within species but do not contribute to divergence. The
      patterns of polymorphism and divergence at charge-altering amino acid sites are
      presented for the Drosophila ND5 gene to examine the evolution of functionally
      distinct mutations. Excess charge-altering polymorphism is observed at the
      carboxyl terminal and excess charge-altering divergence is detected at the amino
      terminal. While the mildly deleterious model fits as a net effect in the
      evolution of nonrecombining mitochondrial genomes, these data suggest that
      opposing evolutionary pressures may act on different regions of mitochondrial
      genes and genomes.

PMID- 8754211
TI  - Relative apparent synapomorphy analysis (RASA). I: The statistical measurement of
      phylogenetic signal.
AB  - We have developed a new approach to the measurement of phylogenetic signal in
      character state matrices called relative apparent synapomorphy analysis (RASA).
      RASA provides a deterministic, statistical measure of natural cladistic hierarchy
      (phylogenetic signal) in character state matrices. The method works by
      determining whether a measure of the rate of increase of cladistic similarity
      among pairs of taxa as a function of phenetic similarity is greater than a null
      equiprobable rate of increase. Our investigation of the utility and limitations
      of RASA using simulated and bacteriophage T7 data sets indicates that the method
      has numerous advantages over existing measures of signal. A first advantage is
      computational efficiency. A second advantage is that RASA employs known methods
      of statistical inference, providing measurable sensitivity and power. The
      performance of RASA is examined under various conditions of branching evolution
      as the number of characters, character states per character, and mutations per
      branch length are varied. RASA appears to provide an unbiased and reliable
      measure of phylogenetic signal, and the general approach promises to be useful in
      the development of new techniques that should increase the rigor and reliability
      of phylogenetic estimates.

PMID- 8754212
TI  - Episodic evolution and rapid divergence of members of the rat multigene family
      encoding the salivary prohormone-like protein SMR1.
AB  - In rodents, the variable coding sequence (VCS) multigene family displays
      extensive evolutionary divergence in the protein-coding region. While certain VCS
      genes coding for proline-rich proteins (hPR-PB, mMSG1, rPR-VB1) are conserved in
      primates and rodents, others seem to be specific to certain genera. This appears
      to be the case for the Rattus genes forming the A-subclass. This subclass is
      composed of three genes in R. norvegicus and probably five genes in R. rattus.
      The first described VCSA gene (Rn. VCSA1) was found to encode a prohormone-like
      protein named SMR1 (-VA1), expressed mainly in the submandibular glands (SMG) of
      male rats. To further understand the evolution of this variable multigene family,
      we have cloned the two additional genes (Rn. VCSA2 and Rn. VCSA3) forming the R.
      norvegicus A-subclass and three VCSA genes (Rr. VCSA1a, b and Rr. VCSA2) of R.
      rattus. The putative SMR1 proteins encoded by all these genes display the same
      prohormone-like structure as Rn. SMR1-VA1. However, we observe a polymorphism in
      some internal cleavage sites which suggests that multiple processing of the SMR1
      proteins could result in the liberation of peptides differing in structure and
      length. The phylogenetic analysis of the sequences reveals that the duplication
      events giving rise to the VCSA1, -A2, and -A3 progenitors were anterior to the R.
      norvegicus and R. rattus split, and that a VCSA1 duplication event likely
      occurred specifically in R. rattus. A striking observation is that the coding
      sequences of the VCSA genes have rapidly diverged from their ancestors. Along all
      branches of the phylogeny, the nonsynonymous divergence rate is identical or
      superior to the synonymous divergence rate. We suggest that frequent changes in
      functional requirements are mainly responsible for the episodic evolution and the
      rapid divergence of the VCSA genes.

PMID- 8754213
TI  - Amylase gene structures in primates: retroposon insertions and promoter
      evolution.
AB  - Amylase transcription in the human salivary gland results from the evolutionary
      juxtaposition of two inserted elements, a gamma-actin pseudogene and an
      endogenous retrovirus, to create an unusual salivary-specific promoter. We
      utilized these structures as molecular tags to characterize the amylase genes in
      extant primates by polymerase chain reaction amplification of promoter fragments
      from genomic DNA. Six distinct amylase promoter structures were identified, which
      allowed us to infer the structures of common ancestors and trace the evolution of
      the modern human amylase promoters. Our data show that integration of the
      pseudogene and retrovirus were evolutionarily recent events. The gamma-actin
      pseudogene integrated after the divergence of the New World monkeys from the
      primate ancestral tree, and the retrovirus integrated later, after the divergence
      of the Old World monkeys. The New World monkey amylase promoter represents the
      mammalian amylase precursor structure before integration of the two retroposons.
      Two distinct amylase genes were identified in the Old World monkeys, one with a
      complete gamma-actin pseudogene insert and another novel structure with a
      truncation of the gamma-actin sequences. We demonstrated abundant amylase
      expression in the saliva of an Old World monkey, indicating that the endogenous
      retrovirus is not required for amylase transcription in the primate salivary
      gland.

PMID- 8754214
TI  - Gene conversion and natural selection in the evolution of X-linked color vision
      genes in higher primates.
AB  - During higher primate evolution, gene conversion seems to have occurred often
      between the red and green photo-pigment genes, which are tandemly linked on the X
      chromosome. To understand this phenomenon better, intron 4 sequences of the red
      and green pigment genes of a male human (an Asian Indian), a male chimpanzee, and
      a male baboon were amplified by PCR and sequenced. The data show that the intron
      4 sequences between the two genes have been strongly or completely homogenized in
      the three species studied. Apparently recent gene conversion events have occurred
      in introns 4 of the red and green pigment genes in humans and chimpanzees. Two or
      more conversion events may have occurred at different times in introns 4 of the
      two pigment genes in baboons. The divergence between the two genes is
      significantly lower in intron 4 than in exons 4 and 5 in each species, contrary
      to the usual situation that introns evolve faster than exons. It is most likely
      that strong natural selection for maintaining the distinct functions of exons 4
      and 5 of the red and green pigment genes has acted against sequence
      homogenization of these exons.

PMID- 8754215
TI  - Localization of sequences regulating ancestral and acquired sites of esterase6
      activity in Drosophila melanogaster.
AB  - We have broadly defined the DNA regions regulating esterase6 activity in several
      life stages and tissue types of D. melanogaster using P-element-mediated
      transformation of constructs that contain the esterase6 coding region and
      deletions or substitutions in 5' or 3' flanking DNA. Hemolymph is a conserved
      ancestral site of EST6 activity in Drosophila and the primary sequences
      regulating its activity lie between -171 and -25 bp relative to the translation
      initiation site: deletion of these sequences decrease activity approximately 20
      fold. Hemolymph activity is also modulated by four other DNA regions, three of
      which lie 5' and one of which lies 3' of the coding region. Of these, two have
      positive and two have negative effects, each of approximately twofold. Esterase6
      activity is present also in two male reproductive tract tissues; the ejaculatory
      bulb, which is another ancestral activity site, and the ejaculatory duct, which
      is a recently acquired site within the melanogaster species subgroup. Activities
      in these tissues are at least in part independently regulated: activity in the
      ejaculatory bulb is conferred by sequences between -273 and -172 bp (threefold
      decrease when deleted), while activity in the ejaculatory duct is conferred by
      more distal sequences between -844 and -614 bp (fourfold decrease when deleted).
      The reproductive tract activity is further modulated by two additional DNA
      regions, one in 5' DNA (-613 to -284 bp; threefold decrease when deleted) and the
      other in 3' DNA (+1860 to +2731 bp; threefold decrease when deleted) that
      probably overlaps the adjacent esteraseP gene. Collating these data with previous
      studies suggests that expression of EST6 in the ancestral sites is mainly
      regulated by conserved proximal sequences while more variable distal sequences
      regulate expression in the acquired ejaculatory duct site.

PMID- 8754216
TI  - Evolution of the mammalian mitochondrial control region--comparisons of control
      region sequences between monotreme and therian mammals.
AB  - The platypus mitochondrial control region has been cloned and sequenced.
      Comparative analysis of this sequence with the published control region sequences
      of several other mammalian species has identified regions of sequence consensus
      that are conserved throughout the Mammalia. Regions predicted to form
      thermodynamically stable secondary structures in the platypus are also homologous
      to such putative structures in other species. In addition to these conserved
      structures, the platypus mitochondrial control region also contains a number of
      unusual features, including two regions of repetitive sequence, one of which
      gives rise to pronounced length variation between animals. Possible functions for
      the conserved structures and a mechanism for the generation of the control region
      length variation are proposed with respect to our current understanding of
      mitochondrial replication and transcription.

PMID- 8754217
TI  - Loss of meiosis in Aspergillus.
AB  - If strictly mitotic asexual fungi lack recombination, the conventional view
      predicts that they are recent derivatives from older meiotic lineages. We tested
      this by inferring phylogenetic relationships among closely related meiotic and
      strictly mitotic taxa with Aspergillus conidial (mitotic) states. Phylogenies
      were constructed by using DNA sequences from the mitochondrial small ribosomal
      subunit, the nuclear ribosomal internal transcribed spacers, and the nuclear 5.8S
      ribosomal gene. Over 920 bp of sequence was analyzed for each taxon. Phylogenetic
      analysis of both the mitochondrial and nuclear data sets showed at least four
      clades that possess both meiotic and strictly mitotic taxa. These results support
      the hypothesis that strictly mitotic lineages arise frequently from more ancient
      meiotic lineages with Aspergillus conidial states. Many of the strictly mitotic
      species examined retained characters that may be vestiges of a meiotic state,
      including the production of sclerotia, sclerotium-like structures, and hulle
      cells.

PMID- 8754218
TI  - Evidence that two types of 18S rDNA coexist in the genome of Dugesia (Schmidtea)
      mediterranea (Platyhelminthes, Turbellaria, Tricladida).
AB  - Sequences of 18S ribosomal DNA (rDNA) are increasingly being used to infer
      phylogenetic relationships among living taxa. Although the 18S rDNA belongs to a
      multigene family, all its copies are kept homogeneous by concerted evolution
      (Dover 1982; Hillis and Dixon 1991). To date, there is only one well
      characterized exception to this rule, the protozoan Plasmodium (Gunderson et al.
      1987; Waters, Syin, and McCutchan 1989; Qari et al. 1994). Here we report the 1st
      case of 18S rDNA polymorphism within a metazoan species. Two types (I and II) of
      18S rDNA have been found and sequenced in the platyhelminth Dugesia (Schmidtea)
      mediterranea (Turbellaria, Seriata, Tricladida). Southern blot analysis suggested
      that both types of rDNA are present in the genome of this flatworm. This was
      confirmed through sequence comparisons and phylogenetic analysis using the
      neighbor-joining method and bootstrap test. Although secondary structure analysis
      suggests that both types are functional, only type I seems to be transcribed to
      RNA, as demonstrated by Northern blot analysis. The finding of different types of
      18S rDNAs in a single genome stresses the need for analyzing a large number of
      clones whenever 18S sequences obtained by PCR amplification and cloning are being
      used in phylogenetic reconstruction.

PMID- 8754219
TI  - Recognizing the forest for the trees: testing temporal patterns of cladogenesis
      using a null model of stochastic diversification.
AB  - Computer simulations are developed and employed to examine the expected temporal
      distributions of nodes under a null model of stochastic lineage bifurcation and
      extinction. These Markovian models of phylogenetic process were constructed so as
      to permit direct comparisons against empirical phylogenetic trees generated from
      molecular or other information available solely from extant species. For
      replicate simulated phylads with n extant species, cumulative distribution
      functions (cdf's) of branching times were calculated, and compared (using the
      Kolmogorov-Smirnov test statistic D) to those from three published empirical
      trees. Molecular phylogenies for columbine plants and avian cranes showed
      statistically significant departures from the null expectations, in directions
      indicating recent and ancient species' radiations, respectively, whereas a
      molecular phylogeny for the Drosophila virilis species group showed no apparent
      historical clustering of branching events. Effects of outgroup choice and
      phylogenetic frame of reference were investigated for the columbines and found to
      have a predictable influence on the types of conclusions to be drawn from such
      analyses. To enable other investigators to statistically test for nonrandomness
      in temporal cladogenetic pattern in empirical trees generated from data on extant
      species, we present tables of mean cdf's and associated probabilities under the
      null model for expected branching times in phylads of varying size. The
      approaches developed in this report complement and extend those of other recent
      methods for employing null models to assess the statistical significance of
      pattern in evolutionary trees.

PMID- 8754220
TI  - Proliferation of direct repeats near the Oenothera chloroplast DNA origin of
      replication.
AB  - The spacer between the 16S and 23S rRNA genes of the chloroplast DNA has been
      implicated as an origin of replication in several species of plants. In the
      evening primrose, Oenothera, this site was found to vary greatly in size, with
      plastid genomes (plastomes) being readily distinguished. To determine whether
      plastome "strength" in transmission could be correlated with variation at oriB,
      the 16S rRNA-trnI spacer was sequenced from five plastomes. The size variation
      was found to be due to differential amplification (and deletion) of combinations
      of sequences belonging to seven families of direct repeats. From these
      comparisons, one short series of direct repeats and one region capable of forming
      a hairpin structure were identified as candidates for the factor that could be
      responsible for the differences between strong and weak plastome types. Ample
      sequence variation allowed phylogenetic inferences to be made about the
      relationships among the plastomes. Phylogenetic trees also could be constructed
      for most of the families of direct repeats. The amplifications and deletions of
      repeats that account for the size variation at oriB are proposed to have occurred
      through extensive replication slippage at this site.

PMID- 8754221
TI  - Synonymous codon bias is related to gene length in Escherichia coli: selection
      for translational accuracy?
AB  - The levels of synonymous codon bias is shown to be positively correlated to gene
      length in Escherichia coli genes which are thought to be expressed at similar
      levels; these are genes whose products are present in multimeric proteins in
      equimolar amounts. It is argued that the positive correlation could be caused by
      selection to avoid missense errors during translation. Since the cost of
      producing a protein is proportional to its length, selection in favor of codons
      which increase accuracy should be greater in longer genes, and long genes should
      therefore have higher synonymous codon bias. It is also shown that there is
      variation in synonymous codon use which is independent of either expression
      level, gene length, amino acid composition, or chromosomal location. This
      variation is consistent with selection for translational accuracy but may have
      other origins.

PMID- 8754222
TI  - Rampant horizontal transfer and duplication of rubisco genes in eubacteria and
      plastids.
AB  - Previous work has shown that molecular phylogenies of plastids, cyanobacteria,
      and proteobacteria based on the rubisco (ribulose-1,5-bisphosphate
      carboxylase/oxygenase) genes rbcL and rbcS are incongruent with molecular
      phylogenies based on other genes and are also incompatible with structural and
      biochemical information. Although it has been much speculated that this is the
      consequence of a single horizontal gene transfer (of a proteobacterial or
      mitochondrial rubisco operon into plastids of rhodophytic and chromophytic
      algae), neither this hypothesis nor the alternative hypothesis of ancient gene
      duplication have been examined in detail. We have conducted phylogenetic analyses
      of all available bacterial rbcL sequences, and representative plastid sequences,
      in order to explore these alternative hypothesis and fully examine the complexity
      of rubisco gene evolution. The rbcL phylogeny reveals a surprising number of gene
      relationships that are fundamentally incongruent with organismal relationships as
      inferred from multiple lines of other molecular evidence. On the order of six
      horizontal gene transfers are implied by the form I (L8S8) rbcL phylogeny, two
      between cyanobacteria and proteobacteria, one between proteobacteria and
      plastids, and three within proteobacteria. Alternatively, a single ancient
      duplication of the form I rubisco operon, followed by repeated and pervasive
      differential loss of one operon or the other, would account for much of this
      incongruity. In all probability, the rubisco operon has undergone multiple events
      of both horizontal gene transfer and gene duplication in different lineages.

PMID- 8754223
TI  - The evolutionary history of the amylase multigene family in Drosophila
      pseudoobscura.
AB  - In Drosophila pseudoobscura, the amylase (Amy) multigene family is contained
      within a series of inversions, or gene arrangements, on the third chromosome. The
      Standard (ST), Santa Cruz (SC), and Tree Line (TL) inversions are central to the
      phylogeny of arrangements, and have clusters of other arrangements derived from
      them. The gene arrangements belonging to each of these three clusters have a
      characteristic number of Amy genes, ranging from three in ST to two in SC to one
      in TL. This distribution pattern can reflect a history of either duplications or
      deletions, although the data available in the past did not permit a decision
      between these alternatives. We provide unambiguous evidence that three Amy genes
      were present before the divergence of the ST, SC, and TL arrangements. Thus, the
      current status of the Amy multigene family is the result of deletions in the TL
      and SC arrangements, which created three new pseudogenes: TL Amy2-psi, TL Amy3
      psi, and SC Amy3-psi. Analysis of pseudogene sequences revealed that, in the SC
      and ST arrangements, pseudogene evolution has been retarded, most likely due to
      the homogenization effect of gene conversion. Finally, by determining the
      original copy number, we have reconstructed the evolutionary history of the Amy
      multigene family and linked it with the evolution of the central gene
      arrangements.

PMID- 8754224
TI  - Unequal synonymous substitution rates within and between two protein-coding
      mitochondrial genes.

PMID- 8754225
TI  - Mitochondrial DNA migration events in yeast and humans: integration by a common
      end-joining mechanism and alternative perspectives on nucleotide substitution
      patterns.

PMID- 8754226
TI  - Outbreak of cyclospora infection in North America.

PMID- 8754227
TI  - Assessing substance use disorder in persons with severe mental illness.
AB  - Assessment of dually diagnosed patients consists of three steps: detection,
      diagnosis, and specialized assessment for treatment planning. Each of these is
      informed by recent research.

PMID- 8754228
TI  - Treatment of co-occurring substance abuse and major mental illness.
AB  - A model for the treatment of co-occurring substance abuse and major mental
      disorders is proposed. The model integrates empirically grounded strategies
      applicable to substance abuse problems into the context of outpatient mental
      health treatment.

PMID- 8754229
TI  - Group treatment for dually diagnosed clients.
AB  - Group treatment is a widely practiced intervention for persons with dual
      diagnoses. This chapter reviews the rationale for group treatment and discusses
      four different approaches to group intervention: twelve-step, educational
      supportive, social skills, and stagewise treatment.

PMID- 8754230
TI  - Housing for persons with co-occurring mental and addictive disorders.
AB  - Homelessness is a far too common outcome for persons with dual diagnoses. This
      chapter discusses existing housing barriers and suggests housing, treatment, and
      support services responsive to population need.

PMID- 8754231
TI  - Family support for persons with dual disorders.
AB  - Families are critically important sources of housing, financial support, and
      direct care for persons with dual disorders.

PMID- 8754232
TI  - Cost-effective treatment for persons with dual disorders.

PMID- 8754233
TI  - Comorbid substance use disorder: prevalence, patterns of use, and course.
AB  - Research on the prevalence, patterns, and course of substance use disorders in
      severe mental illness gives key insights into the complex interaction of
      substance use and mental disorder. Understanding the literature on comorbidity
      has implications for the design of clinical services and for the direction of
      future research in the field.

PMID- 8754235
TI  - The electronic patient record: who is at risk?

PMID- 8754234
TI  - Medicine on the Internet, summer '96.

PMID- 8754236
TI  - New technology on the Internet.

PMID- 8754237
TI  - Pocket-sized electronic clinical referencing.

PMID- 8754238
TI  - Building a student computer lab.

PMID- 8754239
TI  - Quality and efficiency at the point of care.

PMID- 8754240
TI  - The Virtual Hospital: an IAIMS integrating continuing education into the work
      flow.
AB  - Researchers at the University of Iowa are developing an integrated academic
      information management system (IAIMS) for use on the World Wide Web. The focus is
      on integrating continuing medical education (CME) into the clinicians' daily work
      and incorporating consumer health information into patients' life styles. Phase I
      of the project consists of loosely integrating patients' data, printed library
      information, and digital library information. Phase II consists of more tightly
      integrating the three types of information, and Phase III consists of awarding
      CME credits for reviewing educational, material at the point of patient care,
      when it has the most potential for improving outcomes. This IAIMS serves a
      statewide population. Its design and evolution have been heavily influenced by
      user-centered evaluation.

PMID- 8754241
TI  - The interactive patient: a multimedia interactive educational tool on the World
      Wide Web.
AB  - To develop a physician-friendly continuing medical education tool for use on the
      World Wide Web, and to improve physicians' clinical and history taking skills,
      developers at Marshall University designed a multimedia interactive patient
      encounter for a Web server. Any physician with access to the Internet can use
      this program to take a history, perform a physical examination, order laboratory
      and radiologic studies, and submit a diagnosis and treatment plan. The system
      evaluates the user's performance electronically and delivers CME credits by mail.
      The Interactive Patient has been embraced by the medical community, with many
      institutions providing links to this new tool and hundreds of physicians using
      it. The enthusiasm of most users demonstrates that combining education with fun
      enhances the learning experience.

PMID- 8754242
TI  - Telepreventive medicine.
AB  - There have been dramatic improvements in health during the past 50 years, and
      public health measures have made a major contribution. Much of public health
      consists of information transfer. The application of telecommunications
      technology to public health and preventive medicine would enhance our ability to
      transmit information and improve global health. The idea of telemedicine has
      received considerable attention but has not thus far included preventive
      medicine. We have outlined a global electronic health network with seven main
      components: connectivity, telemonitoring of disease, "distance education" for
      public health workers, electronic connection of nongovernment organizations, a
      combined degree in public health and communications, an electronic scientific
      research server, and a home page on the World Wide Web. A commitment to the
      integration of telecommunications and public health holds great promise for
      improving the health status of the world's population.

PMID- 8754243
TI  - Exploring the functions of World Wide Web-based electronic medical record
      systems.
AB  - The recent increase in publications regarding implementations of World Wide Web
      based electronic medical record systems makes it necessary to compare different
      systems and to understand how they support particular needs. This paper develops
      a framework and a coarse metric by which these Web-based systems can be
      classified and eventually compared.

PMID- 8754244
TI  - The information driveway: data management for the rest of us.

PMID- 8754245
TI  - Newborn Touch: a CAI program in neonatal pathology.

PMID- 8754246
TI  - Molecular genetic approaches to mammalian brain and behavior: an introduction.
AB  - Two of the goals of behavior genetics have been to identify individual genes with
      effects on brain and behavior and to determine the mechanism(s) for effects of
      individual genes on brain and behavior. With classical genetics, this would have
      consisted of identifying a gene by mapping it to a chromosome and of determining
      the pathways for its effects, tracing back from behavior or brain to the gene.
      Molecular genetics brings other approaches to these issues. Findings with
      molecular methods also lead to hypotheses with regard to mechanisms for effects
      of individual genes on brain or behavior. In this issue examples of molecular
      genetic approaches are described for perceptual (color vision and olfaction),
      motivational (circadian rhythms and sexual behaviors), learning and memory, and
      pathological (alcohol-related and schizophrenia) aspects of mammalian behavior.

PMID- 8754247
TI  - Molecular genetics of human color vision.
AB  - The significant advances in our understanding of color vision has been due to the
      convergence of information from behavioral and molecular genetic analyses. The
      molecular biology of the visual pigments; molecular genetic basis of variation in
      normal and abnormal color vision, and regulation of the genes at the LWS-MWS
      pigment gene locus are discussed.

PMID- 8754248
TI  - Molecular genetics of mammalian olfaction.
AB  - Olfaction plays a crucial role in the survival of most animal species; it is
      remarkable in its ability to recognize and discriminate numerous airborne
      molecules, yet is one of the least understood senses. The advent of molecular
      genetic approaches has greatly contributed to disclosing some of the mysteries in
      olfaction. The identification of olfactory-specific proteins, the discovery of
      the large receptor gene family, and the first insight into the mechanisms
      governing chemosensory gene expression hold great promise for an eventually
      detailed understanding of a sensory system that was previously considered as
      hardly accessible for research at the molecular level.

PMID- 8754249
TI  - Light, immediate-early genes, and circadian rhythms.
AB  - Many diverse behaviors exhibit clear circadian rhythms in their expression. In
      mammals, these rhythms originate from a neural circadian clock located in the
      suprachiasmatic nuclei (SCN). Recently, signaling pathways activated by light in
      the SCN have begun to be identified. A specific set of immediate-early genes is
      induced by light in the SCN, and their expression is correlated with the
      resetting of circadian behavioral rhythms. These light-regulated immediate-early
      genes offer multiple inroads into the biology of the SCN: first, they are
      functional markers for the activation of SCN neurons by light; second, they can
      direct us to the upstream light-activated (and clock-regulated) signal
      transduction pathways which mediate their induction; and finally, they encode
      transcription factor proteins which may play a role in the molecular mechanism of
      resetting the circadian clock.

PMID- 8754251
TI  - Application of antisense DNA method for the study of molecular bases of brain
      function and behavior.
AB  - The antisense DNA method has been used successfully not only in vitro but also
      with in vivo systems to block effectively the expression of specific genes. An
      increasing number of studies have shown that antisense DNA administered directly
      into the brain can modify various kinds of behaviors. These findings strongly
      suggest that the antisense DNA method can be widely used as a powerful tool for
      the study of the molecular bases of behavior. In addition to traditional methods
      of behavioral genetics, the antisense DNA method may provide a new approach for
      the study of the effects of gene in behavioral function. In this article, we
      review recent studies reporting in vivo effects of antisense DNA on brain
      function and behavior.

PMID- 8754252
TI  - A role for immediate-early transcription factors in learning and memory.
AB  - This article summarizes recent studies from the long-term potentiation (LTP),
      long-term depression (LTD), and behavioral learning literature, indicating that
      immediate-early genes (IEGs) may play an important role in learning and memory.
      The LTP studies suggest that synaptic modifications occurring during NMDA
      receptor-mediated hippocampal LTP and LTD are stabilized by the protein products
      of the krox family of IEGs (as well as by brain-derived neurotrophic factor,
      BDNF). Activation of muscarinic receptors also induces members of the krox as
      well as the fos and jun family (jun-B but not c-jun) IEGs in hippocampal neurons
      and this action may be involved in the facilitatory effects of muscarinic
      receptor activation on both hippocampal LTP and learning. The possible role of
      IEGs in the learning-enhancing effects of cholinergically mediated hippocampal
      theta is also discussed. Finally, I review a number of recent studies showing IEG
      expression in brain neurons after behavioral learning. Together these results
      suggest some role for select IEGs (e.g., Krox 24) in learning and memory,
      although definitive studies using antisense DNA technology are required to
      establish any causal links. In particular, IEGs may be critical components of the
      signal transduction cascade that links NMDA and muscarinic receptors to the
      neuronal genome and ultimately to the generation of permanent modifications in
      neuronal biochemistry that provides the substrate for learning.

PMID- 8754254
TI  - Molecular genetic analysis of the role of GABAergic systems in the behavioral and
      cellular actions of alcohol.
AB  - Recent studies implicate the inhibitory neurotransmitter gamma-aminobutyric acid
      (GABA) in many neurochemical actions of ethanol and a variety of behavioral
      responses to acute and chronic ethanol treatment. However, the molecular
      mechanisms responsible for genetic differences in initial neurochemical or
      behavioral sensitivity to ethanol, and adaptation following chronic or repeated
      ethanol administration, remain to be elucidated. Pharmacogenetic research will
      increasingly move toward mapping, cloning, identification, and functional
      analysis of the genes underlying the actions of ethanol. The approaches discussed
      here permit molecular analysis of both known and previously unknown genes
      regulating behavioral sensitivity to ethanol. The synthesis of molecular methods
      and behavioral genetics offers immediate hope for delineating the role of the
      GABA(A) receptor complex, and other determinants of GABAergic neurotransmission,
      in determining genetic variation in behavioral responses to ethanol.

PMID- 8754253
TI  - The use of null mutant mice to study complex learning and memory processes.
AB  - A number of neural substrates have been proposed to mediate complex learning and
      memory processes in mammalian organisms. One strategy for testing the involvement
      of a particular gene in learning and memory is to create a mouse line with a null
      mutation in that gene. Recently, embryonic stem cell-based gene-targeted
      homologous recombination techniques have been employed to create a number of such
      mutant mouse lines that do not express interesting candidate genes. These animals
      have been examined for impairments in several complex learning paradigms which
      are known to depend on the integrity of the hippocampus. In this review several
      complex learning and memory paradigms are described, the techniques to create
      null mutants are reviewed, and the results of recent studies with null mutants
      are described. Finally, the limitations for interpretation of behavioral data
      using null mutants are discussed.

PMID- 8754256
TI  - Genetic diversity among selected ethnic subpopulations of Australia: evidence
      from three highly polymorphic DNA loci.
AB  - Immigration has been the principal source of population growth in Australia since
      European settlement began in 1788. As a result, the Australian gene pool has been
      constantly evolving, particularly over the last 50 years, during which peoples
      from many European and Asian countries have arrived in large numbers. Three
      highly polymorphic DNA loci (D1S80, HLA-DQA1, and human THO1) are used to assess
      the level of diversity among six immigrant subpopulations that compose
      significant elements in present-day Australia, namely, Asians, Italians, Greeks,
      Slavs, Middle Easterners, and a "general white" sample. Asian migrants are the
      most distinctive of the groups at all three loci, possessing the highest
      frequencies of alleles HLA-DQA1*3 and D1S80*27, *28, and *30, and an
      exceptionally high frequency of THO1*9. The European-derived groups cluster
      together separately from Asians, but Greeks are characterized by their
      frequencies of HLA-DQA1*2 and *4 and THO1*8. Middle Easterners lie on the fringe
      of the European cluster. When the results of the present study are combined with
      worldwide data for each of the three DNA markers, these hypervariable loci,
      especially D1S80 and THO1, are able to differentiate the major groups of humans.
      The level of population differentiation revealed by RST values for the three DNA
      markers is similar to or even less than the values recorded for the less
      polymorphic classical genetic markers. Therefore these three DNA markers are
      highly suitable for both forensic purposes and the investigation of population
      relationships.

PMID- 8754255
TI  - Molecular genetics of psychopathologies: a search for simple answers to complex
      problems.
AB  - Molecular genetics is helping define the contribution of genetic involvement in
      behavioral disorders. At this time, however, a severely limiting factor for DNA
      linkage studies of these disorders remains the definition of the phenotype. An
      example of this is found in the group of studies examining linkage of
      schizophrenia to the 5q location. Although various broad clinical interpretations
      of the schizophrenia phenotype were used to test for linkage, all but one study
      reported findings negative for linkage of schizophrenia to the 5q area. We offer
      a strategy based on family studies using segregation data of behavioral subtypes.
      We apply this strategy using molecular genetic technology to our study of
      psychopathology in patients. This approach offers the possibility of a clearer
      definition of the phenotype and is suggested for use in both linkage and
      association studies of neuropsychiatric disorders.

PMID- 8754250
TI  - Hormonal and neurotransmitter regulation of GnRH gene expression and related
      reproductive behaviors.
AB  - Gonadotropin-releasing hormone (GnRH), having a highly conserved structure across
      mammalian species, plays a pivotal role in the control of the neuroendocrine
      events and the inherent sexual behaviors essential for reproductive function.
      Recent advances in molecular genetic technology have contributed greatly to the
      investigation of several aspects of GnRH physiology, particularly steroid hormone
      and neurotransmitter regulation of GnRH gene expression. Behavioral studies have
      focused on the actions of GnRH in steroid-sensitive brain regions to understand
      better its role in the facilitation of mating behavior. To date, however, there
      are no published reports which directly correlate GnRH gene expression and
      reproductive behavior. The intent of this article is to review the current
      understanding of the way in which changes in GnRH gene expression, and
      modifications of GnRH neuronal activity, may ultimately influence reproductive
      behavior.

PMID- 8754257
TI  - Genetic polymorphism of the 3' VNTR region of the human dopaminergic function
      gene DAT1 (human dopamine transporter gene) in the Mongolian population.
AB  - The hypervariable region of the dopamine transporter gene (DAT1) was amplified
      from samples in the Mongolian population. This region includes a variable number
      of tandem repeats of a 40-bp core unit in the 3' untranslated region of DAT1.
      Vandenbergh et al. (1992) reported variability in the number of repeats of this
      3' flanking region ranging from 3 to 11 times in white and black populations. We
      examined polymorphism at the DAT1 locus in 78 native Mongolian subjects. We found
      alleles with 7 to 13 repeats, which is different from the findings of Vandenbergh
      et al. (1992). The allele distribution of the Mongolian population is similar to
      that in the Japanese population, reported previously by Nakatome et al. (1995).
      Chi-square analysis showed a significant lack of homogeneity between our findings
      in Mongolian subjects and those reported previously in white and black
      populations. The DAT1 locus was estimated to have a heterozygosity index of
      14.1%, and the polymorphic information content was calculated to be 0.16.

PMID- 8754258
TI  - Sub-Saharan influence on the Canary Islands population deduced from G6PD gene
      sequence analysis.
AB  - In a screening of glucose-6-phosphate dehydrogenase (G6PD) A variants in the
      Canary Islands and northwest African populations by electrophoresis and posterior
      gene sequencing, the common A+ 376G and A- 202A/376G and the rare A- 376G/968C
      mutations were found. In addition, three new silent C-->T transitions have been
      detected at nucleotides 759 (exon 7), 1338 (exon 11), and 1573 (exon 13). Canary
      Island and North African samples share sub-Saharan haplotypes with Equatorial
      Guineans. The slave trade seems the most probable origin of the African
      haplotypes found in the Canary Islands.

PMID- 8754259
TI  - HLA affinities of Iyers, a Brahmin population of Tamil Nadu, South India.
AB  - Seventy-four randomly sampled Iyers, a Brahmin population of Tamil Nadu and
      preachers and followers of the Advaita philosophy, living in Madurai, were
      studied for their HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ, C4A, C4B, and BF
      polymorphisms and compared with other populations. HLA alleles A1, A11.1, A24,
      A33, B35, B44, B51, B52, B57, Cw4, Cw6, Cw7, DR4, DR7, DR8, DR10, DR11, DR15, and
      DQ1 and C4A*3, C4A*4, C4A*6, C4A*Q0, C4B*1, and BF*S were represented in 15% of
      the samples studied. HLA alleles A25, A69, Cw3, Cw8, B45, B14, B39, B18, B50, and
      B56 were not identified. Various populations of Tamil Nadu were compared, but the
      Iyers of Madurai formed a separate cluster with Sourashtrans of Madurai and major
      group 4 (various Brahmin populations of Tamil Nadu); hill tribes (Irulas,
      Malayalis, and Badagas) and caste groups in the plains (Kallars and Nadars)
      formed distinct clusters. Comparison of the Iyers with other Indian and world
      populations revealed that Iyers form a distinct branch of the Indo-European and
      Central Asian tree. The Bhargavas of Lucknow, another Brahmin caste group from
      Uttar Pradesh, did not cluster with the Iyers but clustered with Central Asian
      populations. The Punjabis of Delhi clustered with European and Middle Eastern
      populations. Studies on two-locus haplotypes of Iyers revealed unique haplotypes
      in them (A26-B8, A33-B44, A33-Cw7, A1-B57, B8-DR3, B44-DR7, DR7-DQ2, C4A*32
      C4B*Q0, and C4A*6-C4B*2), most of which were not identified in the Bhargavas of
      Lucknow and the Punjabis of Delhi. Thus it is possible that various Brahmin
      populations of India differ in their origin, migration, and settlement, although
      all of them adopted Hinduism in ancient times. A comparison of haplotypes in
      Iyers with the world population reveals a sharing of haplotypes with Southeast
      Asian populations. This implies that the ancestors of the Iyers of Madurai, who
      originated in the Eurasian steppes or Central Asia, might have migrated to India
      through Southeast Asia, thus developing the prevalent haplotypes en route.

PMID- 8754260
TI  - Population biology of human aging: segregation analysis of bone age
      characteristics.
AB  - The main goal of the present study is to elucidate the extent to which primary
      characteristics of bone aging are determined by major gene effects. We report the
      results of a complex segregation analysis of bone mineral density (BMD) and
      osseographic score (OS) carried out on an array of pedigrees from rural
      Turkmenia. Both variables showed a significant correlation with age and thus were
      adjusted. However, the correlations with body height, weight, body mass index,
      and obesity indexes were negligible. The results of the segregation analysis
      performed on BMD clearly indicate major gene effects on BMD variation. The
      Mendelian transmissibility hypothesis with two codominant alleles was chosen as
      the best-fitting and most parsimonious model. Under this hypothesis 50-60% of
      total variation in BMD, depending on bone area, can be attributed to a major gene
      effect, and the frequency of the allele determining the higher value of bone
      density is between 30% and 38% in the Turkmenian population. Regarding the OS,
      segregation analysis provided evidence supporting intergenerational
      transmissibility of this characteristic and yet the Mendelian model was rejected.

PMID- 8754261
TI  - Is there increased fertility in adult males with the sickle cell trait?
AB  - Different proposals have been offered to explain the polymorphism of the sickle
      cell hemoglobin gene. One of these proposals (Eaton and Mucha 1971) suggested
      that differential fertility of male subjects with the sickle cell trait
      contributes to the persistence and stability of the sickle cell gene frequency.
      Eaton and Mucha claimed that oligospermia, induced by hyperpyrexia, is a less
      common problem in these subjects because they probably have milder and shorter
      episodes of fever from malaria infection than subjects with a normal genotype. We
      have looked for evidence to support this hypothesis by comparing the testicular
      function, testicular size, and serum concentrations of the reproductive hormones
      in adult male subjects with the sickle cell trait and in an age-matched group of
      subjects with normal hemoglobin genotype. The mean serum concentration of
      testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin of
      both groups, measured by radio-immunoassay, were not statistically different from
      each other. Also, there was no detectable difference in any of the common indexes
      of semen quality between the two groups. The testicular volume index and several
      anthropometric indexes of subjects with the sickle cell trait and subjects with
      the normal hemoglobin genotype were also statistically similar. The results
      suggest that gonadal function is similar in adult males with the normal genotype
      and those with the sickle cell trait. Any increase in fertility observed in the
      latter group is probably due to extragonadal factors.

PMID- 8754262
TI  - Is there seasonality in human ovulation?
AB  - To study seasonality in human ovulation in a direct way, we measured the
      occurrence of ovulation in infertile patients with spontaneous menstrual cycles
      (< 6 weeks) who visited the fertility clinic at the University Hospital Nijmegen
      in the Netherlands for the first time in 1991 or 1992 (n = 407). Ovulation was
      detected using serial transvaginal ultrasound and midluteal progesterone
      measurement and was performed during one screening cycle. The frequency of
      ovulatory cycles per month varied from 73% to 93% (not statistically
      significant). No seasonal pattern in ovulation was found in subfecund Dutch women
      with spontaneous menstrual cycles. This finding was not confounded by the effects
      of age of the women, body mass index, or disorders that could influence
      ovulation.

PMID- 8754263
TI  - Repetition of the same pair of surnames in marriages in Albanian Italians, Greek
      Italians, and the Italian population of Campobasso Province.
AB  - The isolation of a population as a result of any boundary leads to a kinship
      mating pattern, the extent of which can be measured by the frequency of repeated
      pairs of surnames in actual marriages compared with that in random pairings. The
      repeated pairs within surname lineages (RPw) method can be used to assess random
      repetitions and the endogamous or exogamous behavior of a population. The RPw
      method was applied to data from grandparent surnames of children living in 45
      Albanian Italian and 13 Greek Italian villages of southern Italy and Sicily and
      in 22 Italian villages of Campobasso Province (central Italy). The total mean RPw
      was 0.02782 in Albanian Italians, 0.01993 in Greek Italians, and 0.03427 in the
      Italian-speaking population. When RPw was subdivided into its components and
      compared with random and marital isonymy, the low level of inbreeding shown by
      the two southern Italian ethnic minorities and by the Italian population of
      Campobasso Province could be accounted for by the subdivision of the populations.

PMID- 8754264
TI  - Circannual pattern of autistic births: reanalysis in three ethnic groups.
AB  - Seasonal variations in births of autistic subjects have been reported for the
      United States, Canada, Sweden, Japan, and Israel. Here, data from England, Japan,
      and Israel are reanalyzed using spectral analysis for the cosine function. A
      sample of 583 autistic births occurring over 40 years (1947-1989) is meta
      analyzed, focusing on rhythmicity. Major periodicities of 17.6, 18.6, and 21.8
      years, on which minor periodicities ranging from 2.2 to 4.1 years were
      superimposed, yielded the best-fitting cosine function to significantly explain
      variance of autistic birth patterns. It is interesting that the function composed
      of a major period with several minor periods is remarkably similar in each of the
      three ethnic groups. In all three countries the acrophases (calculated function)
      aggregate in the period 1963-1970. In light of this apparent universality of
      rhythms in autistic births across continents, we call for further investigations
      into the role of environmental factors, possibly viral pandemics, in the etiology
      of autism.

PMID- 8754265
TI  - [Proteolytic enzymes: subcellular localization, properties and participation in
      neuropeptide metabolism].
AB  - The subcellular localization and properties of enzymes involved in processing of
      neuropeptide precursors and in inactivation of active peptide forms are
      considered. It is concluded that the role of proteolytic enzymes in neuropeptide
      metabolism is determined by their subcellular localization and substrate
      specificity.

PMID- 8754266
TI  - [Cytochrome bd: structure and properties].
AB  - Literary evidence concerning the arrangement and functioning of the cytochrome bd
      complex is reviewed with particular emphasis on ligand-binding properties of the
      enzyme. Some novel data on cytochrome bd interaction with carbon monoxide,
      cyanide and hydrogen peroxide are presented.

PMID- 8754267
TI  - [Structure of the O-specific polysaccharide from Proteus mirabilis O30].
AB  - Based on acid hydrolysis, methylation, and one- and two-dimensional 1H- and 13C
      NMR spectroscopy, including homonuclear and 1H, 13C heteronuclear correlation
      spectroscopy (COSY) and rotating-frame nuclear Overhauser effect spectroscopy
      (ROESY); it was found that the O-specific polysaccharide chain of the
      lipopolysaccharide of the bacterium Proteus mirabilis O30 is a hexosamino
      glucuronan built up of tetrasaccharide repeating units having the following
      structure: [formula: see text] The degree of O-acetylation of 2-acetamido-2
      deoxyglucose is about 70%.

PMID- 8754268
TI  - [Structure of the O-specific polysaccharide chain from Burkholderia (Pseudomonas)
      solanacerum ICMP 750, 8093, 8115, 7864, and 7945 lipopolysaccharides].
AB  - Lipopolysaccharides (LPS) have been isolated from the cells of phytopathogenic
      bacteria Burkholderia (Pseudomonas) solanacearum strains (representatives of I,
      II and IV biovars) using mild acid hydrolysis followed by gel permeation
      chromatography of carbohydrate residues on Sephadex G-50 to yield five O-specific
      polysaccharides (O-PS). The O-PS structures were established by 13C-NMR
      spectroscopy. It has been found that O-PS have a linear or branched structure.
      The former represents a tetrasaccharide comprising three L-rhamnose residues and
      one N-acetylglucosamine residue. The differences between the strains are in the
      configuration (alpha or beta) and type [(1 --> 2) or (1 --> 3)] of the link
      between D-GtcpNAc and L-Rhap. The branched structure represents a xylosylated
      version of the linear structure and consists of pentasaccharide repeating units.
      The bacterial strains under study may be represented by multiple structural
      types, O-PS, involving both linear and branched repeating units. There is no
      correlation between the O-PS structure and strain specificity for any particular
      plant host.

PMID- 8754269
TI  - [Activity of phosphoinositide-specific phospholipase C in rabbit nerves at rest
      and during stimulation].
AB  - The dependence of rabbit sciatic nerve PtdIns-specific phospholipase C activity
      Ca2+ and pH has been studied. The enzyme was found to hydrolyze PtdInsP2 in a
      Ca(2+)-dependent manner. The maximal activity was detected at 1mM CaCl2 for the
      cytosolic enzyme and at 0.1 mM CaCl2 for membrane-bound enzyme. The pH optima
      determined for the cytosolic and particulate enzymes were pH 6.0 and 7.0,
      respectively. The enzyme activity in the cytosolic fraction was shown to remain
      practically constant under nerve stimulation (200 impulses/sec, 5 min), whereas
      in microsomal fraction it was 44% greater compared to the resting nerve. It is
      suggested that the enzyme is bound to membrane in intact axon, therefore the
      rapid signal (depolarizing stimulus) transduction into axon becomes possible.

PMID- 8754270
TI  - [Antigenic activity of Burkholderia solanacearum lipopolysaccharides].
AB  - The interaction of the antiserum against Burkholderia solanacearum ICMP 8110
      cells with lipopolysaccharides from 19 strains of B. solanacearum differing in O
      specific polysaccharide structure has been studied using ELISA. No correlation
      was found between the O-specific polysaccharide structure and serological
      activity of the lipopolysaccharide. Most of the lipopolysaccharides isolated from
      B. solanacearum strains (except for 4157, 767 and 7942) displayed cross
      reactivity with the tested antiserum. These data indicate that the strain under
      study pertains to the same serogroup. It cannot be excluded that some
      nonidentified components in the O-specific polysaccharide structure are
      responsible for the serological activity of the lipopolysaccharide.

PMID- 8754271
TI  - [Detection of a new small RNA, induced by heat shock, in wheat seed ribosomes].
AB  - Changes in the small cytoplasmic RNA (scRNA) composition have been examined in
      wheat embryos exposed to heat shock conditions. A novel scRNA of about 135
      nucleotides in length termed as 5.3S RNA, has been detected for the first time.
      With a rise in temperature from 26 degrees C up to 37 degrees C, the amount of
      5.3S RNA increases 5 to 6 times. It was found that 5.3S RNA is localized
      predominantly on ribosomes and also in the fraction of native 40S ribosomal
      subunits known to contain translation preinitiation complexes. Upon dissociation
      of 80S monoribosomes under high ionic strength conditions (0.5 M KCl), 5.3S RNA
      remains to be bound to the 40S subunit, thus indicating their strong and specific
      interaction. 5.3S RNA is neither a precursor of the 5S rRNA nor a discrete
      fragment of high molecular weight ribosomal RNA. It was supposed that 5.3S RNA is
      transcribed by RNA polymerase III and involved in protein synthesis regulation in
      plant cells under heat shock conditions at the level of translation initiation.

PMID- 8754272
TI  - [Effect of specific ligands on heat inactivation of muscle glycogen phosphorylase
      b].
AB  - It has been shown that the rate constant, k, for thermal inactivation of rabbit
      skeletal muscle glycogen phosphorylase b decreases as the enzyme concentration
      increases. This effect is interpreted within the framework of a kinetic model
      which includes two parallelly occurring processes, namely: phosphorylase b
      denaturation in solution and denaturation of the enzyme absorbed on test-tube
      walls. The contribution of the latter process increases with a decrease in the
      enzyme concentration. The protective effect of the allosteric activator (AMP),
      allosteric inhibitors (glucose 6-phosphate and FMN) and the competitive inhibitor
      (glucose) against heat denaturation of glycogen phosphorylase b has been
      demonstrated. Quantitative analysis of the dependence of the rate constant, k, on
      concentration of AMP, glucose 6-phosphate and FMN allows the calculation of
      microscopic constants for dissociation of phosphorylase b complexes with these
      ligands for the given experimental conditions as equal to 0.34, 0.50 and 0.30 mM,
      respectively. The S-shaped dependence of the rate constant of thermal
      inactivation on glucose concentration points to the existence of positive
      cooperative interactions between glucose-binding sites in the dimeric molecule of
      phosphorylase b (nH = 1.8).

PMID- 8754273
TI  - [Modification of the ligand load and structure of human serum albumin with
      different methods of isolation].
AB  - The influence of isolation procedures on physico-chemical properties of human
      serum albumin (HSA) has been studied using differential scanning calorimetry and
      infrared spectroscopy. Fractionation of blood plasma with polyethylene glycol
      (PEG) followed by ion-exchange chromatography produced healthy donor albumin
      whose melting thermograms were identical to those of the HSA in non-fractionated
      plasma. The endotherms of HSA samples isolated by affinity chromatography (AC)
      and native electrophoresis (EP) are bimodal as distinct from monophasic
      endotherms of PEG-HSA preparations. The changes in the melting curves result from
      increased levels of nonesterified fatty acids in AC-HSA samples and modification
      of the protein secondary structure revealed in EP-HSA samples by IR-spectroscopy.
      Analysis of HSA melting thermograms in patients with uremia, chronic hepatitis
      and peritonitis revealed that the PEG method permits to preserve, in the greatest
      degree, the thermodynamic features of various "pathological" HSA. The
      experimental results demonstrate the advantage of the PEG technique in isolation
      of native HSA in the norm and under pathology.

PMID- 8754274
TI  - [Kinetics of dissociating inactive tetramers of muscle glycogen phosphorylase b
      in active dimers].
AB  - Recovery of enzymatic activity of rabbit skeletal muscle glycogen phosphorylase b
      preincubated with 1 mM AMP and 0.125 M K2SO4 (0.05 M glycyl-glycine buffer pH
      6.8; 17 degrees C) has been studied. According to sedimentation data,
      preincubation conditions favor the formation of the tetrameric form of the
      enzyme. When registering the kinetics of the enzymatic reaction catalyzed by
      phosphorylase b preincubated with AMP and K2SO4, acceleration of the reaction in
      the course of the enzymatic process was observed. On the basis of kinetic data,
      the rate of constant for the dissociation of phosphorylase b tetramers into
      dimers has been calculated: k = (8.3 +/- 0.3) 10(-3) sec-1 (0.05 M glycyl-glycine
      buffer pH 6.8; 17 degrees C).

PMID- 8754275
TI  - [Study of calcium-binding properties of the Mts-1 protein and its recombinant
      analog using the fluorescent probe Fura-2].
AB  - A procedure based on the ability of Mts-1 to competitively inhibit the formation
      of Fura-2 complexes with Ca(2+)-ions is described. It has been shown that Mts-I
      reversibly inhibits the complex formation between Fura-2 and calcium. The
      efficiency of natural Mts-I isolated from cells of the CSML-100 line and of its
      recombinant analog on the formation of the Fura-2+Ca complex is different. The
      inhibition constant, Ki, for the native protein is equal to 2,4 microM, that for
      the recombinant form is 8.5 microM. The data obtained are suggestive of
      posttranslational modification of Mts-I in cells under in vivo conditions.

PMID- 8754276
TI  - [Post-radiation changes of DNA-protein cross-links and single-stranded DNA breaks
      in cells of various organs in gamma-irradiated rats].

PMID- 8754277
TI  - [NADPH-containing, superoxide-producing lipoprotein fraction from blood serum.
      Isolation, purification, brief characteristics and mechanism of action].
AB  - A procedure for isolation and purification of the lipoprotein fraction from blood
      serum (human, rabbit, bovine, rat) has been developed which includes ion-exchange
      chromatography of the dialyzed serum on DEAE and CM cellulose and DEAE. Sephadex
      as well as gel filtration on Sephadex G-150 and biogel P-150. This fraction was
      purified until denaturation and loss of solubility. The optical purification
      index of this fraction (A280/A430) is 8.5. The fraction has an optical absorption
      spectrum with a maximum at 280 nm and a weakly expressed shoulder at 430 nm, its
      fluorescence spectrum has an excitation maximum at 370 nm and emission maximum at
      430 nm characteristic of NADPH. The protein fraction presumably contains NADPH
      and about 50% of phospholipids. It is assumed that the mechanism of O2 production
      involves Fe3+ reduction to Fe2+ by NADPH and the electron transfer from Fe2+ to
      atmospheric oxygen. Suprol provides a simple and readily accessible source of
      superoxide radicals for the study of their effects on various biosystems.

PMID- 8754278
TI  - [Oxidative processes in the ischemic brain].

PMID- 8754279
TI  - Disruption of mesectodermal lineages by temporal misexpression of the Drosophila
      POU-domain transcription factor, drifter.
AB  - Among the first cells to differentiate in the Drosophila ventral nerve cord, the
      mesectodermal (midline) lineage gives rise to a discrete set of neurons and glia
      previously demonstrated to play an important role in the organization of the
      developing nervous system. The relative simplicity of the midline has allowed the
      elucidation of many aspects of initial lineage commitment and subsequent
      differentiation. Based upon its mesectodermal expression pattern and loss-of
      function phenotype, we have proposed a key role for the Drosophila POU-domain
      transcription factor, drifter (dfr), in mesectodermal lineage development. In
      this study, we have examined the developmental consequences of dfr misexpression
      using transgenic lines expressing wild-type Drifter protein under control of the
      heat-inducible hsp70 promoter. Induction of ubiquitous DFR protein during a
      restricted period of embryogenesis causes a defective axonal phenotype
      characterized by failure of commissure formation. Based on examination of cell
      specific markers for mesectodermal cells, these defects appear to be the result
      of a suppression of single-minded expression resulting in the disruption of
      mesectodermal lineage designation and differentiation. The observed temporally
      restricted sensitivity to DFR expression suggests possible interactions between
      DFR protein and other stage-specific mesectodermal regulatory factors present
      before or after a defined mesectodermal developmental event.

PMID- 8754280
TI  - Vitellogenetic defects in hybrids of the species pair Drosophila virilis and
      Drosophila texana.
AB  - In interspecific matings between the species Drosophila virilis and Drosophila
      texana, female sterility can be observed in F2 backcross females and in F2 hybrid
      females. The results presented in this report show that the female sterility,
      whenever it exists, is due to prevention of vitellogenin synthesis in the fat
      body, but other abnormalities such as defects with the hybrid ovaries are not
      excluded. The observation that sterility appears among females from backcrosses
      suggests that incompatibilities between interspecific genes may cause female
      sterility even in the presence of a complete habloid genome from one or the other
      species. Yet, the parallel observation that female sterility appears only in
      hybrid females with recombinant chromosomes indicates that sterility results when
      conspecific combinations of genes on the same chromosome are broken by
      interspecific recombination.

PMID- 8754281
TI  - Juvenile hormone regulation and developmental expression of a Tenebrio
      desiccation stress protein gene.
AB  - Levels of a 28 kDa hemolymph protein, desiccation stress protein (dsp28), in the
      mealworm beetle, Tenebrio molitor, increase in response to desiccation and cold
      stress and are also developmentally regulated under nonstress conditions. Dsp28
      mRNA is produced in the fat body, and its abundance changes dramatically
      throughout development. Transcript abundance increases throughout larval
      development, drops at pupation, and increases again in adults, the highest levels
      being found in females. The juvenile hormone (JH) analogue, methoprene, increased
      dsp28 transcript accumulation in pupae, suggesting that changing JH titres have a
      role in developmental expression and also perhaps contribute to dsp28 regulation
      during conditions of environmental stress. Genomic DNA, containing the entire
      dsp28 coding region plus 1.3 kb of upstream sequence, was isolated and potential
      regulatory sequences, including putative JH response elements, were identified.

PMID- 8754282
TI  - Arsenic-induced alterations in embryonic transcription factor gene expression:
      implications for abnormal neural development.
AB  - We examined the morphological and molecular consequences of acute in utero
      exposure to teratogenic concentrations of arsenate. The treatment produced a dose
      related increase in neural tube defects, along with a significant alteration in
      the pattern of gene expression for several transcription factors (creb, Hox 3.1,
      Pax3, and Emx-1) that were examined using in situ transcription and antisense RNA
      amplification procedures. On gestational day 9:0, there was a significant delay
      in the embryos progression through neural tube closure, accompanied by a
      significant downregulation of Hox 3.1 expression and a significant upregulation
      of Pax3, Emx-1, and creb. As both Hox 3.1 and Pax3 serve to regulate N-CAM
      expression, it is possible that abnormalities associated with N-CAM may
      compromise neural crest cell migration and normal neural tube closure.

PMID- 8754283
TI  - Mutations in the gene stand still disrupt germ cell differentiation in Drosophila
      ovaries.
AB  - During oogenesis in Drosophila, germ cells appear in sequential clusters of 16
      interconnected cells. The events surrounding the differentiation of these cells
      are not fully understood. Here we present genetic and morphological analysis of
      mutations in the gene stand still (stil). Through complementation analyses we
      have refined the location of this gene to cyological region 49B-C. Our analyses
      of ovaries from ethylmethane sulfonate (EMS)-induced mutant alleles of this gene
      suggest that mutations in the stil gene produce a wide range of phenotypic
      abnormalities, from the absence of germ cells in the most severe alleles, to egg
      chambers with cytoskeletal defects in the less severe alleles. Our results
      suggest a role for this gene in specifying or maintaining a cytoskeletal
      component, with consequences during oogenesis and possibly during germ line sex
      determination.

PMID- 8754284
TI  - Prevalence of streptococcal sorethroat in the school children of Dhaka.
AB  - Beta Haemolytic Streptococcal (BHS) infections and their sequelae Rheumatic Fever
      (RF) and Glomerulonephritis (GN) have a world wide distribution and so pose an
      important health problem. Reports show that there is considerable variation in
      the number of isolations from different groups. Present study intended to find
      out the health status of the school children in relation to streptococcal throat
      infection, in Dhaka Cantonment. It was a cross sectional, observational study.
      During one year period total six hundred and one (601) children were examined
      from one school of Dhaka Cantonment. Prevalence of streptococcus was found to be
      22% among the study population with highest rate (67%) for group-G among BHS
      positive cases. True streptococcal infection was found in 8.7% cases & 2.2% cases
      were true GABHS positive cases. GABHS was significantly higher in large size
      families. Females and children from lower socioeconomic group were at higher
      risk. Females and children of large families may require special attention
      regarding prevention of streptococcal infection and RF/RHD prevention programme.

PMID- 8754285
TI  - Urinary tract infection at a specialist hospital in Saudi Arabia.
AB  - Midstream specimens of urine from inpatients and out patients at King Fahd
      Specialist Hospital in Buraidah, Saudi Arabia, were collected over a period of 12
      months to determine prospectively the frequencies of different causative
      organisms and their antimicrobial susceptibility. A total of 854 from 4157
      specimens (20.54%) gave significant bacterial counts i.e., counts greater than
      10(5) organisms per millilitre. Escherichia coli was the commonest organism
      (50.11%) followed by Klebsiella spp. (28.33%) Pseudomonas spp. (7.84%) and
      Proteus spp. (4.91%). Other bacterial pathogens were Enterococcus spp. (3.98%),
      Acinetobacter spp. (1.84%), Staphylococcus aureus (1.63%), Enterobacter spp.
      (0.35), Staphylococcus epidermidis (0.30%), Haemolytic streptococci B (0.47%) and
      Salmonella paratyphi A (0.12%). In vitro drug sensitivity tests showed
      norfloxacin and nalidixic acid to be very effective for most of the strains of
      the bacterial pathogens. A very high proportion of strains of Escherichia coli
      (86%) and Klebsiella spp. (94.6%) were found to be resistant to ampicillin.

PMID- 8754286
TI  - Screening--a unique way of better health care delivery for ENT patients.
AB  - A few Ear Camps were carried out amongst 25 schools and madrashas of Dhaka City
      having 10,102 pupils, to see the prevalence of ENT diseases and hearing
      impairment. A primary screening was done by the Bangladesh Council for Child
      Welfare (BCCW) with the possibilities of suffering from ear, nose & throat
      diseases with the help of questionnaire and clinical examination by qualified
      doctor. The word "Screening" is used in this paper not in the epidemiological
      sense but to imply primary selection. 1,403 (13.89%) were issued registration
      card for ENT consultation. Five otolaryngologist, one audiometrician, two
      ancillary staffs, BCCW workers, local volunteers and school teachers conducted
      the 3 days long camp. Secondary screening by the otolaryngologists revealed
      pathology in 1,101 students (10.89%). 26 children (0.26%) were attending schools
      with severe hearing loss. ENT diseases appeared to be common in urban school
      children and screened proved to be an efficient method for health care delivery.

PMID- 8754287
TI  - Branchial cleft anomalies--a study of 20 cases.
AB  - Preauricular sinus, branchial cyst, branchial sinus and branchial fistula are the
      result of incomplete obliteration of branchial clefts. Classically these lesions
      have particular sites and nature. The aim of this three years retrospective study
      was to see the prevalence of these conditions as well as the outcome of the
      conventional surgery. Twenty cases of branchial cleft anomalies were reported, of
      which 60% had with preauricular sinus. One case with preauricular sinus had
      recurrence during postoperative follow-up.

PMID- 8754288
TI  - Clinical down staging of cancer cervix with cytology.
AB  - A prospective study was carried out on 1500 patients attending the Gynaecology
      outpatient department of three referral hospitals in Dhaka City. These patients
      were selected on some selected clinical criteria to correlate several clinical
      markers (clinical down staging) with that of Pap's smear for early detection and
      secondary prevention of cancer cervix. Speculum examination and Pap's smear were
      done in all cases. Among 1500 women, 224 had abnormal Pap's smear. Histologic
      examination of specimens from these cases showed chronic cervicitis in 45 cases,
      dysplasia in 84 and squamous cell carcinoma in 95. Carcinoma was found in 130.
      Thus, there were 297 Pap's smear negative cases were biopsied on clinical ground.
      225 cases of invasive carcinoma. From this study, it seems that clinical
      downstaging with cytology programme has to be started immediately throughout the
      country for diagnosis of carcinoma of the cervix in its preinvasive and
      potentially curable stage.

PMID- 8754289
TI  - [Resistance to insulin--pathomechanism, clinical syndromes].

PMID- 8754290
TI  - [Lipid disorders in serum of patients with insulin dependent diabetes mellitus.
      EURODIAB IDDM Complications Study--Krakow].
AB  - The aim of this study was to assess the prevalence of the lipid metabolism
      disorders and their determinants in a group of patients with insulin dependent
      diabetes mellitus, included in the EURODIAB IDDM Complications Study in Krakow
      center. We examined 120 patients with insulin dependent diabetes mellitus.
      Hypercholesterolemia (serum cholesterol > 5,2 mmol/l) was observed in 61,7% of
      patients, hypertriglyceridemia (serum triglycerides > 1,7 mmol/l) in 20,8% of
      patients, hypo-HDL-cholesterolemia (HDL-cholesterol 0,9 mmol/l) in 4,2% of
      patients. The mean values of total and LDL-cholesterol concentrations increased
      and mean HDL and HDL3-cholesterol concentration decreased from I to III tertile
      of HbAlc concentration. The results of this study indicate the high prevalence of
      hyperlipidemia and need of monitoring serum lipid concentration in IDDM patients.

PMID- 8754291
TI  - [Polymorphonuclear neutrophil adhesion in patients with diabetes mellitus].
AB  - The adherence of polymorphonuclear neutrophils was evaluated in patients with
      type I and type II diabetes as well as in group of elderly people. The adherence
      of these cells suspended in plasma: autologous, control, inactivated, zymosan
      activated and in FMLP solution was estimated. The adherence of polymorphonuclear
      neutrophils obtained from controls after the suspension of cells in diabetic
      plasma was also estimated. The estimations were also performed after the heat
      inactivation of diabetic plasma and its activation by zymosan. The obtained
      results seem to indicate that the enhanced adherence of polymorphonuclear
      neutrophils in diabetic patients is due to the presence of heterogeneous plasma
      factors.

PMID- 8754292
TI  - [Disorders of bone tissue metabolism in patients in diabetes mellitus type one].

PMID- 8754293
TI  - [Results of kinesis therapy in patients with diabetic macroangiopathy of the
      lower extremities].
AB  - In 30 patients with diabetes type II and macroangiopathy of lower extremities,
      physical training was applied. This treatment was carried on in our Clinic for
      average 4 weeks. The following methods were applied: individual exercises of legs
      once or twice daily for 30-minutes, training in brine swimming pool for 30
      minutes every-day, treatment walks with proportioning effort. Value of physical
      effort was not more than 30-40% max. pulse rate. The examination was performed
      before and after the programme of treatment. The examination included the
      following parameters: subjective test on cycloergometer, examination of blood
      flow velocity by Doppler method and biochemical examination of glycaemia and
      lipidemia. We found improvement in intermittent claudication distance,
      significant subjective improvement in velocity of blood flow in lower
      extremities. In our opinion physical vascular training is a valuable method of
      mono-operative treatment of vascular disease of legs in diabetic patients.

PMID- 8754294
TI  - [A study of natural history in 208 patients with atherosclerosis of lower limb
      arteries and diabetes mellitus].
AB  - In the recent years a constant increase of the number of surgical patients with
      associated diabetes mellitus is observed. Surgical risk is still higher and
      therapeutic results are worse than in patients without diabetes mellitus. Many
      years of experience of our department in the surgical treatment of lower limb
      atherosclerosis (A0) in patients with diabetes, and also the previously published
      results of studies make possible drawing of conclusions and formulating of a
      general view. The studies were carried out in 208 patients with A0 and diabetes
      mellitus. On admission, 65.9% of the patients had IV degrees of limb ischaemia
      according to Fontaine. Vascular operations in these patients accounted only for
      25% of all operations and were performed in 37% of patients. Amputations
      accounted even for 53.7% of all operations, and among them major amputations
      accounted for 56.3%. The early and remote results of the operations carried out
      were subjected to statistical analysis and presented using cumulated indices.

PMID- 8754295
TI  - [Dietary habits of obese patients with type 2 diabetes mellitus].
AB  - For assessment of the way of nutrition of obese patients with diabetes mellitus
      type 2 (insulin-dependent), questionnaire method was used including dietary
      history data. The study was carried out in 50 patients during weight-losing
      treatment in our institute. It was found that the mean energy value of daily food
      ration of the patients was relatively high, exceeding both the value of predicted
      energy expenditure and the standard values. This was not true, however, of all
      patients. Among the studied patients, 32% of persons were not eating excessively,
      and some of them ate even less than the standards; only 24% of obese patients
      could have been regarded as hyperfagous. Significant dietary faults concerned
      also the food composition, that is mainly excessive fat content which accounted
      even for 46% of calorie value of daily food ration. Among other dietary faults
      the following should be mentioned: low vegetable content, additional eating
      between meals, and irregular taking of meals. The weight-losing treatment with
      simultaneously conducted health education contributed to the change of dietary
      habits of the observed patients.

PMID- 8754296
TI  - [Diabetes mellitus complicating pregnancy].
AB  - Of the total 25381 delivered in our Department, in the time from January 1987 to
      December 1993, 175 (0,69%) were from pregnancies with complicated by diabetes
      mellitus. 171 of that number ended with healthy babies (172), which is a
      relatively satisfactory outcome. Only 4 patients lost their babies. They were 3
      patients admitted to our programme late in their pregnancy period. Already during
      their first medical examination the diagnosis was a) nonviable pregnancy in 1
      case and b) multiple, congenital defects in the remaining 2 cases. 1 baby was
      died three days after delivery (congenital heart disease). All patients attended
      classes of special diabetes mellitus education in the Pathology Ward. Each
      patient underwent programmed control visits by obstetrician and diabetologist;
      metabolic therapy reached the level of near normoglycemia. In each case the time
      of delivery was selected individually. As result of such approach majority of
      patients gave natural birth. Only in 29 cases (16,6%) caesarean operation was
      performed. The reason for caesarean operation in 12 of the 29 cases was a
      previous operation of this kind. In the other 5 cases natural birth was
      impossible, because of the big foetus. Observation of the newborn babies during
      their first days of life showed that most of them suffered from the following
      complications: hypoglycaemia (39,8%), hyperbilirubinemia (25,1%), anaemia (12,9%)
      and hypocalcaemia (7%). All the babies being in generally good condition were
      discharged from the hospital on the 5th-10th day together with their mothers. It
      seems that such good results could obtained owing to special programme, which
      could by applied also in Regional Gynecological-Obstetrical Ward with help of a
      local diabetologist.

PMID- 8754297
TI  - [Intestinal bypass for treatment of obesity--to use or not and why?].

PMID- 8754298
TI  - [Diabetic neuropathy: overview of clinical problems].

PMID- 8754300
TI  - [Pathogenesis of chronic diarrhoea after surgery for extreme obesity].

PMID- 8754299
TI  - [Risk factors of microangiopathy in patients with non-insulin dependent diabetes
      mellitus].

PMID- 8754301
TI  - [The role of muscle, adipose tissue and liver in development of metabolic
      syndrome].

PMID- 8754302
TI  - [Health education as a method of treating psycho-emotional disorders in patients
      with diabetes mellitus].

PMID- 8754303
TI  - [Scientific basis for self care of chronically ill patients: medical education as
      a new form of care--in light of personal observations].

PMID- 8754304
TI  - [Level and dynamics of empathy in I and VI year students at the Medical Academy
      of Medicine in Gdansk].
AB  - Empathy is and important element in achieving didactic goals in the field of
      communication skills. It is a valuable feature particularly in the family doctor
      practice. 353 students (210 female and 143 male) from the first and last year of
      medical school were survived by using the psychological questionnaire-"Emotional
      Empathy Scale" by A. Mehrabian and N. Epstein, evaluating emotional aspects of
      empathy. The findings suggest that the level of empathy is higher among women
      than among men from the first year. The difference is statistically significant.
      During six years of medical education there is a significant decrease of empathy
      skill in women, specially in its emotional aspect. These students represent the
      lack of willingness in contact with people having problems. According to these
      findings we decided to continue our research to check the hypothesis concerning
      reasons of decreasing level of empathy in medical students.

PMID- 8754305
TI  - [Significance of philosophy and psychology in teaching family medicine].

PMID- 8754306
TI  - [Problems, organization and methods of a regional diabetic out-patient clinic
      based on analysis of personal experience].

PMID- 8754307
TI  - [Efficacy and tolerance of axetil cefuroxime for treatment of chronic urinary
      tract infection relapse in patients with diabetes mellitus].

PMID- 8754308
TI  - [Computed tomography and pulmonary pathology].
AB  - By using the data on 570 cases with lung cancer, 49 with various types of
      tuberculosis, 13 with benign tumours, and 223 with acute and chronic inflammatory
      lung diseases, the authors of the paper analyze their diagnosis by using the
      currently available techniques X-ray computed tomography (CT). The role of CT is
      compared with the techniques of the so-called classical roentgenology. In the
      authors' opinion, CT for central lung cancer is of the greatest importance in its
      peribronchial malignancy while in peripheral lung cancer it provides an objective
      insight into the involvement of the pleura. As for a large group of pulmonary
      diseases which may be subsumed under the heading of inflammatory diseases, CT has
      proved to be also a highly effective diagnostic technique that correctly
      interprets some complicated cases to make an accurate diagnosis. By and large,
      computed tomography for pulmonary tuberculosis is more effective in the
      assessment of the extent of a process, in case-finding and in the definition of
      the characteristics of cavities, small ones in particular (as small as 3-4 mm),
      which are present in the consolidated infiltrates, tuberculomas and individual
      foci, as well as in the detection of small seeding foci. The authors consider CT
      to become one of the leading techniques in the diagnosis of major pulmonary
      disease.

PMID- 8754309
TI  - [Emergency radiation study in thoracoabdominal gunshot wounds].
AB  - The paper considers the main issues of a primary emergency radiology in thoracic
      and abdominal gunshot injury proceeding from some practical experience gained in
      examining and surgically treating 271 victims with this injury. It defines
      specific indications to examine either anatomic region and expediency of applying
      various radiation techniques and procedures. Recommendations are given on the
      optimum scope of radiology to solve different diagnostic problems. By and large,
      principles and policy of radiation study are defined in thoracic and abdominal
      gunshot injuries.

PMID- 8754310
TI  - [The x-ray diagnosis of a predisposition to nephrogenic pulmonary edema in
      glomerulonephritis patients].
AB  - To develop criteria for determining predisposition to pulmonary edema in patients
      with glomerulonephritis, clinical, laboratory and X-ray examinations were made in
      697 patients with glomerulonephritis at different stages of its development. X
      ray examination included chest tele X-ray and its densitometric analysis. Twenty
      two patients underwent computerized tomography with histographic analysis. In 106
      patients, X-ray findings were compared with the volume of circulating blood,
      cardiac and stroke indices. Changes in the lungs and pleural cavities were found
      in 22.7%, pulmonary edema was revealed in 15.7% of the patients. The
      prognostically unfavourable criteria for the development of pulmonary edema were
      found to be Stage II pulmonary venous hypertension with hypervolemia and
      peripheral edemas. The densitometrically detected increase in the density of the
      lower lungs in patients with Stage II venous hypertension suggests early
      manifestations of interstitial edema of the lung and the narrowing of the
      histogram angle limited by its ascending and descending lines is indicative of
      the fact that interstitial edema progresses to alveolar one.

PMID- 8754311
TI  - [The comprehensive diagnosis and treatment of patients with bronchitis
      deformans].
AB  - A total of 1067 patients aged from 15 to 82 years who suffered from deforming
      bronchitis were examined. All the patients underwent X-ray examination, forced
      external respiration test, bronchofibroscopy with biopsy and radionuclide study
      of the lungs whose results were the basis for establishing a diagnosis of
      deforming bronchitis with an accuracy of 99.8%. Therapeutical bronchoscopies made
      in patients with deforming bronchitis were an effective therapeutical tool in
      96.9-98.1% of cases.

PMID- 8754312
TI  - [The diagnosis and treatment of atrophic bronchitis deformans].
AB  - Ninety-seven patients were treated with laser radiation. A treatment course
      involved 5 to 7 exposures to radiation every second day. An exposure lasted 300
      sec. As a result of treatment, cough completely ceased in 94 patients (96.9%).
      There was also a positive dynamics in the ultrastructural study of biopsy
      specimens taken prior to and following the therapy.

PMID- 8754313
TI  - [Expiratory tracheal stenosis].
AB  - The paper presents the results of X-ray study of 152 patients with bronchial
      asthma which has been made to detect the collapsing trachea. The patients were
      treated at a specialized pulmonological unit of the S. P. Botkin City Clinical
      Hospital and referred for X-ray examination for diagnosis of the collapsing
      trachea. It outlines the procedure for X-ray detection of the collapsing trachea
      and its severity. The procedure is easy-to-use and it is not a burden to
      patients. In terms of its techniques, the proposed procedure is similar to that
      of the Sokolov diaphragmatic motility examination. The examination revealed no
      collapsing trachea in 38 out of 152 patients, while degree I stenosis was
      diagnosed in 54, degree II in 43, and degree III in 8. Moreover, 9 patients were
      found to have tracheomegaly. No expiratory stenosis was detected in a control
      group of 30 patients. An element of subjectivity is sure to be present in the
      assessment of examination results. A difference in tests made by different
      patients is also of significance. The simplicity of the procedure, easiness for
      patients to perform it, possible outpatient application, sufficient efficiency
      provide a basis for recommending it to be used by therapeutical roentgenologists
      in their practical work.

PMID- 8754314
TI  - [The diagnosis of the dislocation and microdislocation of an endocardiac
      electrode based on x-ray and electrocardiographic study data].
AB  - The X-ray films and ECG records were analysed in 11 cases of dislocation and 20
      cases microdislocation of the endocardial lead in patients with monopolar
      ventricular pacing. In 3 patients lead was dislocated into the right ventricle
      cavity, in 2 patients--in the another heart cavity, in 6 cases lead dislocation
      was negligible. In 20 cases of microdislocation the fluctuation all intracardiac
      parts of the endocardial lead not only his distal end was revealed. Therefore it
      is better to call this complication of heart pacing "the endocardial lead
      instability". The X-ray picture of the negligible lead dislocation was identical
      to microdislocation: a thickening unclear contour of the distal lead end. The ECG
      picture in cases of dislocation was different from microdislocation: the lack of
      pacing contrary to pacing preserved in cases of microdislocation. All patients
      with dislocation and microdislocation had high amplitude spike of pacemaker
      impulses.

PMID- 8754315
TI  - [A case of a mediastinal epidermoid cyst].

PMID- 8754316
TI  - [2 cases of a papillary cystic tumor of the pancreas].

PMID- 8754317
TI  - [The logical-gnoseologic sources of diagnosis (what was Niccolo Paganini's
      illness?)].

PMID- 8754319
TI  - [The discovery of x-rays].

PMID- 8754318
TI  - [Tuberculosis of the respiratory organs and the current possibilities for its x
      ray diagnosis].

PMID- 8754320
TI  - [Treatment of goiter in adolescents in surgical practice--personal observations].
AB  - Fifty one patients 12-19 years old were operated on because of different thyroid
      diseases (1.7% of total amount 3029 patients after surgical treatment). There was
      no post-operative complication (except of 2 cases of temporary vocal cord
      paresis). Late results of surgical treatment in adolescents were not
      significantly different then in other groups. Presence of the symptoms of
      clinical or subclinical hypothyreosis or rarely recurrence of thyrotoxicosis in
      patients with toxic nodular goitre after surgical treatment, however, makes the
      treatment worst, particularly important in this age group. Suppression therapy of
      thyroid hormones was administrated in all patients with simple nodular goitre and
      with thyroid cancer. All patients were followed up in our outpatient clinic.
      During the follow-up from 6 months to 10 years no recurrence of goitre or thyroid
      cancer was observed.

PMID- 8754321
TI  - [The effect of hemodialysis on levels of beta-endorphin in serum of patients with
      chronic renal failure treated with erythropoietin].
AB  - In CRF patients many endocrine abnormalities were observed. BE levels are
      elevated in CRF patients and HD treatment do not decrease it. In the other hand
      during rHu-EPO therapy many changes previously observed during CRF, in hormones
      concentrations partially are normalised. The aim of present study was to find
      answer on the following questions: 1. Are there any differences in plasma BE
      levels between hemodialysed CRF patients treated with rHu-EPO and in untreated,
      2. Does rHu-EPO therapy have any influence on plasma BE level during HD session?
      Fourty CRF hemodialysed patients were divided into 2 groups. Group 1 consist of
      18 patients (10 female and 8 male with mean age 41.6 +/- 16.3 years) treated with
      rHu-EPO during last 3-9 months (50 u.i./kg b.m.) intravenously after each HD
      session. Group II consist of 22 patients (11 both female and male with mean age
      46.2 +/- 17.9 years) untreated with rHu-EPO. From CRF patients blood sample were
      taken 4 times: before HD, in 120 min. of HD in front of and behind dialyzer and
      in 240 min. This procedure was provided follow HD sessions using bicarbonate
      buffer with polysulphone dialyzer. Control plasma BE concentration was
      established from 40 healthy subjects with mean age 39.6 +/- 12.7 years as 24.9 +/
      7.6 pmol/l. Plasma BE level was assessed using RIA method (INCSTAR). Mean plasma
      BE level in control group was significantly lower then in CRF groups. There were
      no differences in plasma BE levels between examined CRF groups. We concluded that
      elevated in CRF patients plasma BE concentration does not modify by rHu-EPO
      treatment and that in both examined groups plasma BE concentration does not
      change during HD session.

PMID- 8754322
TI  - [Risk and circumstances in which people are bitten by dogs in Cracow--
      observations from the Consulting Clinic of Infectious Diseases].
AB  - Inquiries about incidence of bites people by dogs have been made in the
      Consulting Ward for prophylactics of rabies of Chair and Department of Infectious
      Diseases in Cracow. There are frequent cases of people bitten by dogs, which
      usually occur in the streets. Victims are usually young. In the most cases there
      are not connection between victim's behavior and incidence. Dogs however bite
      without an understandable reasons frequently when they are controlled by their
      owners. The owners of the dogs often are not aware of their responsibility to
      prevent their dogs from biting passers-by.

PMID- 8754323
TI  - [Arterial hypertension complicated by aortic dissection. Clinical analysis,
      results of conservative treatment].
AB  - Detailed analysis of 21 patients suffering from arterial hypertension complicated
      by aortic dissection, who were treated non-surgically was performed. Signs and
      symptoms of aortic dissection appeared the most frequently in the age between 50
      and 69. In 14 (66.7%) cases proximal (type A) and in 7 (33.3%) distal (type B)
      dissection were diagnosed. During acute phase 15 patients complained of pain and
      6 did not. Smoking and family history of arterial hypertension were the commonest
      risk factors in this group. Proximal dissection was more frequently connected
      with painful course of the dissection whereas distal with painless. Detailed
      analysis of clinical data and non-invasive treatment during acute phase (first 14
      days since onset of pain) was performed. During ambulatory observation which
      lasted 3-75 month (mean 34.3 month) 5 (25%) patients died, 15 (75%) are still
      alive.

PMID- 8754324
TI  - [Evaluation of right ventricular function in patients with hypertrophic
      cardiomyopathy].
AB  - The aim of the study was the estimation of the right ventricular function in
      patients with hypertrophic cardiomyopathy (HC). 20 patients, 14 men and 6 women
      of age 23-50 with echocardiography diagnosed hypertrophic cardiomyopathy were
      examined. Equilibrium gated radionuclide angiography was performed in all
      patients. Right and left ventricle ejection fraction (EF), 1/3 first ejection
      fraction (1/3EF), maximal and average rate of emptying (MER, AER), time to peak
      emptying (TTPE), 1/3 first filling fraction (1/3FF), maximal and average rate of
      filling (MFR, AFR), time to peak filling (TTPF) and MFR/MER ratio were
      calculated. Analysing function of right ventricle in patients with HC impaired
      diastolic function was observed. MFR was 1.44 +/- 0.54EDV/s,AFR-0.95 +/-
      0.24EDV/s, 1/3 FF-0.49 +/- 0.09. Positive correlation between right and left
      ventricle MFR was found (r = 0.62; p < 0.01). Mean value of RVEF was 40.8 +/- 7%,
      1/3EF-17.5 +/- 5%, MER-1.88 +/- 0.4EDV/s, AER-1.59 +/- 0.4EDV/s. Decreased
      ejection fractions of the right ventricle in patients with the thickest
      interventricular septum were observed. Mean value of the time to peak emptying
      was short (x = 68.6 ms). Regional ejection fractions from septum region of RV
      were decreased. It was the result of the abnormal function of the
      interventricular septum in patients with hypertrophic cardiomyopathy. Indexes of
      RV function in the two groups of patients were also analysed: with and without
      left ventricular outflow tract obstruction. Mean value of RV systolic and
      diastolic function indexes were similar in two groups of patients. In conclusion,
      impairment of the right ventricle diastolic function in patients with
      hypertrophic cardiomyopathy is predominated. The more diastolic function of the
      RV deteriorates the worse diastolic function of the left ventricle remains in
      patients with HC.

PMID- 8754325
TI  - [Evaluation of the antihypertensive efficacy and safety of using sustained
      release verapamil in elderly subjects using ambulatory blood pressure
      monitoring].
AB  - OBJECTIVE: Calcium antagonists are commonly used drugs in the treatment of
      hypertension in elderly patients. One of the drugs of this group is verapamil.
      Especially its slow release formula is convenient for use in elderly patients
      (drug is given once daily). The aim of our study was to evaluate the
      antihypertensive efficacy of 240 mg slow release verapamil given once daily in
      elderly hypertensives using ambulatory blood pressure monitoring (ABPM). We also
      evaluated the safety of this slow release formula using trough to peak ratio.
      DESIGN AND METHODS: Twenty hypertensives of mean age 67.5 +/- 5.3 were enrolled
      into the study. Our study was performed using double-blind, placebo-controlled
      cross-over study design. After a 2-week wash-out period 24-hour ABPM was
      performed for the first time and then twice: after 2 weeks of placebo or 240
      verapamil slow-release and after 2 weeks of verapamil or placebo treatment. The
      readings prior to and after the treatment were taken using the same procedure.
      Blood pressure measurements were recorded every 15 minutes between 7.00 and 23.00
      and every 30 minutes between 23.00 and 7.00. RESULTS: Verapamil treatment
      statistically significantly reduced (p < 0.05) mean 24 hour systolic blood
      pressure from 148.88 +/- 7.56 mmHg to 132.24 +/- 6.13 mmHg and diastolic
      respectively from 96.68 +/- 6.05 to 83.04 +/- 5.40 mmHg. Heart rate decreased
      from 77.16 +/- 3.84 BPM to 68.88 +/- 4.41 BPM. Placebo-corrected trough to peak
      ratio was 70% for systolic blood pressure.

PMID- 8754326
TI  - [Cardiotoxic effect of the herec-TNF alpha preparation given intravenously to
      patients with advanced neoplasms].
AB  - The group of 17 patients with advanced neoplastic disease has been treated with
      combined therapy with herec TNF alpha in association with IFN alpha and 5-Fu, the
      cardiotoxic effect of herec TNF alpha administration has been observed. The 30
      minutes intravenous infusion of herec TNF alpha caused statistically significant
      increase of heart rate (in comparison to the previous value). There was also
      observed the decreasing of blood pressure value (about approximately 20-30 mmHg),
      spontaneously disappeared after the infusion ending. Rarely, the heart rhythm
      disturbances i.e.: ventricle extrasystoles in II, III, IV in Lown score have been
      observed. In 2 cases there was additional pharmacological treatment. In the rest
      of the patients the early cardiotoxic effects have not been associated with
      haemodynamic disturbances.

PMID- 8754327
TI  - [Usefulness of standard clotting and fibrinolysis tests for evaluation of
      hemostatic balance in women during the III trimester of pregnancy with slight and
      moderate preeclampsia].
AB  - Usefulness of the standard test to control hemostatic balance has been evaluated
      in 22 pregnant women in III trimester with preeclampsia. Unpregnant and pregnant
      healthy women there were the control group. Increase of the fibrinogen
      concentration and the fibrinolysis time prolongation have been confirmed as well
      as increase of the degradation fibrin/ogen products (FDP/fdp) concentration
      (significantly the highest in the women with moderate preeclampsia). The
      remaining parameters of hemostasis in women with preeclampsia there were within
      laboratory standards.

PMID- 8754328
TI  - [Erectile dysfunction in patients with diabetes].
AB  - Erectile dysfunction is present in approximately 50% of diabetic men. It is most
      often caused by diabetic neuropathy and angiopathy but psychogenic factors are
      also of importance. Treatment includes: elimination of risk factors,
      psychotherapy, pharmacologic treatment and implantation of penile prosthesis.

PMID- 8754329
TI  - [Foreign bodies in the digestive tract].
AB  - In the past two years time 128 patients-prisoners, who had swallowed foreign
      bodies, have been observed. Six anchors and crosses, which had been stuck in the
      esophagus, were immediately and successfully removed endoscopically. Long rods
      and crosses (60 cases) situated mostly in the stomach or descending part of the
      duodenum were operated without any complications. A few weeks delay of operation
      caused the covered perforation of the alimentary tract wall nearly 20% of cases
      and one of which died. Ingested small foreign bodies (less than 10 cm in length)
      are harmless, pass spontaneously through the gastrointestinal tract and don't
      need any surgical intervention. In a few cases those small foreign bodies
      perforated the guts, covered outside the digestive tract without any complaints.

PMID- 8754331
TI  - [The psychopathological systematics of hypochondria].

PMID- 8754330
TI  - [Clinical neurology and the structural-functional organization of the nervous
      system].
AB  - The evidences of the primary role of clinical thinking over the instrumental one
      as well as effectiveness of the ontophylogenetic analysis of clinical phenomena
      are presented. From this point of view the following syndromes were analysed:
      pyramidal, prefrontal cortical epilepsy, amnestic aphasia, deafferent pain. The
      role of denervation hypersensitivity in the epileptogenesis was also examined.
      The clinical data served the basis for validation of the role of antidromal
      irritation in pathogenesis of pain in radicular compression. The problem of
      hemispheres' interactions was analysed too.

PMID- 8754332
TI  - [The current aspects of the social and biological adaptation of epilepsy patients
      in Russia].
AB  - The influence of social alterations on the treatment effectivity and social
      adaptation of 1350 epileptic patients was followed up in 1981-1993. It is shown
      that during the period of social stability clinical observation of such patients
      was quite satisfactory. Therapeutic response reached 98.2% at invalidity rate
      0.2% in 1989. On the contrary, during period of social instability 10.8% of
      patients did not resolve any treatment, the effectiveness of the treatment
      lowered to 76.6%, remission failure occurred in 6%, and the percent of the
      invalids increased to 5.6% of patients. The recommendations are given concerning
      adaptation of epileptics to new social conditions.

PMID- 8754333
TI  - [The immunopathology and immunogenetics of some forms of pediatric epilepsy].
AB  - 52 patients with primary and 42 with secondary generalized epilepsy at the age of
      2-16 years were examined. In all the patients blood content of T- and B
      lymphocytes as well as of their subpopulations (T-helpers, T-suppressors) was
      estimated with the use of monoclonal antibodies. Immunogenetic studies of
      allogenic lymphocytes were also performed in mixed lymphocyte cultures for
      proband and mother. There was an increase of CD4/CD8 ratio (T-helper/T
      suppressor) as well as elevation of B-lymphocytes level in patients with
      secondary generalized form of epilepsy. A positive reaction of allogenic
      lymphocytes from mother and child in mixed cultures was observed in 46 patients
      with primary generalized epilepsy (88.5%), in 16 cases with progredient disease.
      In secondary generalized form of epilepsy it occurred in 7 cases only (16.7%). In
      28 cases of epilepsy with progredient course not only antiepileptic drugs but
      also immunomodulators were used with positive effect in 14 patients.

PMID- 8754334
TI  - [Rasmussen's chronic progressive focal encephalitis].
AB  - Chronic progressive focal encephalitis or Rasmussen encephalitis (RE) is chronic
      brain disease of viral etiology. It is manifested by either partial motor or
      myoclonic seizures combined with hemiparesis. RE was described in detail in a
      girl of 8.5 years. The disease debut was observed at the age of 5.5 and
      manifested in the form of simple partial motor fits with serial episodes of
      secondary generalization. Post-attack hemiparesis was observed from the age of
      7.5 and became permanent after 8. From this time myoclonic fits became constant,
      changed for the worse, memory and attention deteriorated. NMR tomography revealed
      widening and deepening of the Sylvian fissure as well as a focal decrease of left
      temporal area density. The patient was resistant to anticonvulsant, hormonal and
      immunosuppressive drugs. The criteria of RE diagnosis, its difference from
      Kozhevnikov's epilepsy are provided. Estimation of drug and surgical treatment
      effectivity is given. The necessity of early surgical treatment (functional
      hemisphere ectomy) is emphasized.

PMID- 8754335
TI  - [The Guillain-Barre syndrome in herpes zoster patients].
AB  - A rare case of Guillain-Barre syndrome associated with herpes zoster developed on
      the 7th day of eruption in the right dermatoma DII-III in a man of 51 years old.
      The peculiarities of the symptoms, current status, liquor changes have been
      analysed basing on the data from foreign literature on 24 cases of Guillain-Barre
      syndrome (polyradiculoneuritis) associated with herpes zoster.

PMID- 8754336
TI  - [The duration of antiepileptic treatment].
AB  - 110 patients at the age of 18 years and older with different forms of epilepsy
      and epileptic syndromes were observed during 2-15 years after the first fits.
      These patients did not follow medical advice. All of them were either treated for
      short time, irregularly or were not treated at all after their first
      hospitalisation after beginning of epileptic attacks. In spite of violation of
      the treatment regimen, 80 patients experienced improvement, 60 patients achieved
      long-term remissions. It is suggested that even short-term antiepileptic therapy
      may activate the patient's own antiepileptic system. Negative prognostic criteria
      were involvement of the temporal structures, multifocal disease.

PMID- 8754337
TI  - [The effect of endovascular laser therapy and antioxidants on the immune status
      and energy metabolism of patients with treatment-resistant forms of
      schizophrenia].
AB  - The influence of endovascular laser therapy and of antioxidants on clinical
      immunological indices and energy metabolism was analysed in 148 schizophrenic
      patients including 86 patients with shift-like progredient (first group) and 62
      patients with continuous-progredient (second group) forms of the disease.
      Positive trends in psychosis course were observed in 57% of cases in the first
      group and in 41.9% of patients of the second group. Pronounced improvement of the
      immunological indices was observed in patients with positive clinical dynamics:
      decreased peripheral blood immunocytes sensitization to the brain, hepatic,
      thymus tissue antigens as well as ATP elevation which was evidence of the
      improvement of energy metabolism.

PMID- 8754338
TI  - [Vasobral in the treatment of initial atherosclerotic circulatory
      encephalopathy].

PMID- 8754340
TI  - [The diagnosis of epilepsy by using blood analysis for the content of
      autoantibodies to glutamate neuroreceptors].
AB  - The glutamate receptor autoantibody level was studied in blood of 170 epileptic
      patients as well as of 114 control donors (64 patients with nonepileptic cerebral
      pathology and 50 healthy individuals). The elevation of autoantibodies level
      (higher than 140%) was observed in 63.5% of patients with paroxysmal epileptic
      disturbances. This elevation was observed more frequently in the initial period
      of the disease as well as in generalized (convulsive or nonconvulsive) fits
      irrespective of disease etiology. Combined application of the test with EEG
      method permitted to confirm the epileptic nature of the disease in 83.5% of
      cases. The results of repeated analysis of glutamate receptor autoantibody level
      in blood proved to be a significant criterion of the effectiveness of
      anticonvulsive therapy. It also allowed to predict the development of
      posttraumatic epilepsy in individuals with craniocerebral trauma in the past.

PMID- 8754339
TI  - [Cerebral evoked potentials and reaction time studied by selective averaging in
      patients with posttraumatic epilepsy].
AB  - The alteration in brain reactivity and in the consciousness level by measuring
      average evoked potentials as well as of the motor reaction time during the
      periods of the discharge EEG activity were estimated in patients with
      posttraumatic epilepsy. The selective mean quantity method was applied for
      evaluation of the changes in brain reactivity and in consciousness level during
      paroxysmal states. The data obtained allow to estimate brain reactivity
      alteration and consciousness level during paroxysmal EEG pattern.

PMID- 8754341
TI  - [A clinico-physiological and psychological-pedagogical analysis of the structure
      of the defect in cognitive activity in 3 cases of different forms of speech
      pathology].
AB  - Clinical (neurological), neurophysiological (EEG) and psychological examinations
      were carried out in 3 children with general speech defects. These children
      represented 3 main groups with speech disturbances: with speech defects which may
      be logopedically corrected, with speech defect and intact intellectual ability,
      with considerable disturbances of speech and cognitive functions. The
      peculiarities of cognitive disturbances were determined in each group. They were
      manifested in the form of alterations either of basic EEG or of EEG response to
      different stimuli as well as in psychological profile structure.

PMID- 8754342
TI  - [The action of a magnetic field on the bioelectrical activity of the brain in
      healthy subjects and epilepsy patients].
AB  - The influence of reduced geomagnetic field as well as alternative magnetic field
      action on the brain bioelectric activity was analysed in 18 healthy individuals
      and in 20 epileptic patients. The alteration of magnetic field elevated
      functional activity of the brain synchronizing structures and increased either
      epileptic activity or activation of epileptic focus. The data allow to conclude
      that the magnetic field effects are mediated by the deep sensory nerve-pathways.
      The role of the right hemisphere in magnetic field perception and participation
      of back temporal areas in these processes are considered.

PMID- 8754343
TI  - [The structural characteristics of field 17 of the cerebral cortex in the right
      and left hemispheres].
AB  - The results of investigation of the area 17 of visual cortex of human brain in
      left and right hemispheres are described in this article. The main features of
      the structural organization of area 17 concerning the total neurones area,
      neuroglial index as well as the number of big, middle and small neurons in right
      hemispheres are detailed.

PMID- 8754345
TI  - [The development of expert systems for forensic psychiatric evaluation].
AB  - Possible methodological approaches to elaboration of the expert systems in
      forensic psychiatry are presented. These systems are intended for doubtful
      "borderline" cases. The comparison of psychopathologic parameters with
      peculiarities of criminal situation (character of the delinquency, the role of
      the examined person, other factors) is the base of such approach. The advantage
      of clinical logical method over the mathematical one at the present stage of
      forensic psychiatry development is demonstrated.

PMID- 8754344
TI  - [Patient attitude toward the psychiatric hospital].
AB  - The analysis of preconceived ideas about psychiatric hospital performed in 12
      healthy individuals and 21 mental patients permitted the authors to identify
      basic components of negative attitude to psychiatric hospital. The 4 clusters
      were determined: fear of psychic disease; fear concerning the stay in psychiatric
      hospital; negative social attitude toward mental patients, loss of self respect;
      fear of possible social consequences. Essential differences of attitude exists in
      patients and in society. With growing experience of contacts with psychiatric
      service the fear about social discrimination became more significant.

PMID- 8754346
TI  - [Nervous diseases and their treatment in ancient Russia].

PMID- 8754347
TI  - [The life and activities of V. S. Lobzin].

PMID- 8754348
TI  - [Dyslexia: its neuropsychological classification and treatment].

PMID- 8754349
TI  - [Epilepsy with myoclonic absences].

PMID- 8754351
TI  - [The epilepsy of eating].

PMID- 8754350
TI  - [A clinico-genealogical study of a family with juvenile myoclonic epilepsy].
AB  - Juvenile myoclonic epilepsy (JME) is idiopathic generalized epilepsy of teenagers
      characterized by massive myoclonic fits. It is supposed to be of hereditary
      nature with location of the gene on the short arm of the 6th chromosome. A family
      is described where two sibs suffered from JME attacks while their uncle had
      isolated generalized convulsive seizures. The autosomal recessive pattern of JME
      inheritance was suggested. JME gene may be linked to the genes which determine
      photosensitivity and fast generalized spike or polyspike EEG activity. High
      frequency of neuroendocrine disturbances in JME patients is emphasized.

PMID- 8754352
TI  - [Hemimegalocephaly-agyria as the possible cause of the development of the Lennox
      Gastaut syndrome].

PMID- 8754353
TI  - [The search for genetic markers in migraine and epilepsy with different EEG
      variants (a genealogical and dermatoglyphic analysis)].

PMID- 8754354
TI  - [Neonatal bilirubin encephalopathy in perinatal hypoxia].

PMID- 8754355
TI  - [The epileptic attacks of orgasm].

PMID- 8754356
TI  - [Stimulation of the endorphin structures of the brain--a new nondrug treatment
      method].

PMID- 8754357
TI  - [Autism and the autistic syndrome].

PMID- 8754358
TI  - [Oxidant stress--the general mechanism of the damage in nervous system diseases].

PMID- 8754359
TI  - [The use of psychedelic agents in psychotherapy (apropos the article by Iu. P.
      Sivolap and V. A. Savchenkov "Experience in using ketamine preparations in the
      psychotherapy of alcoholism")].

PMID- 8754360
TI  - [Bioethical issues in contemporary medical sciences].
AB  - Unprecedented advances in the natural sciences and in medical technology bring
      many moral issues unknown to previous generations. Very often in their medical
      practice physicians face problems in which the basic role is played by moral
      commitment. In this context, a set of qualitatively new questions emerges: Should
      we continue medical treatment when the patient asks that it be discontinued? Must
      we preserve the life of the irreversibly comatose patients? How to assess moral
      aspects of various forms of donating organs for transplants in evolving social
      cultural situation? Does any religion provide a definition of biological death
      that would be inconsistent with the definition provided by the medical sciences?
      To answer such ethical questions that emerge in our evolving culture, there is an
      urgent need for interdisciplinary discussions developed by scientists,
      philosophers, and theologians. In a philosophically justified attitude of
      Christian personalism, any life has an unique value, though it cannot be regarded
      as an absolutely highest value (The Catechism of the Catholic Church, p. 2289).
      The donation of the organs should be regarded as an act of love. To be an act of
      human person, the decision of donation should be expressed in a free and
      deliberate, manne. In this perspective, the principle of the presumed consent is
      assessed critically because it implies hierarchy of values in which pure
      pragmatism is appreciated more than the love to our neighbours (The Catechism...
      p. 2296). Certainly, the standpoint of pragmatism as such must not be assessed
      negatively; the sacredness of life, its dignity, God-dependence and objective
      value cannot be, however, adequately expressed in purely pragmatic terms. The
      latter categories are basic also in providing Christman answer to may ethical
      questions raised in contemporary medical sciences.

PMID- 8754361
TI  - [Universalism as a concept of medicine in the XXI century].

PMID- 8754362
TI  - [Pharmacologic treatment of chronic congestive heart failure].
AB  - Congestive heart failure (CHF) continues to be a lethal end stage of
      cardiovascular diseases caused by hypertension, coronary heart disease, valve
      deformity, diabetes and cardiomyopathy. Current therapy for CHF can maintain
      function, improve quality of life, and prolong survival. Diuretics, angiotensin
      converting enzyme inhibitors (ACE), and digoxin remain in standards of therapy.
      Diuretics remains an important component of the symptomatic management of
      patients with CHF, but severely II patients may require additional agents. One
      option frequently used in patients who exhibit resistance to loop diuretics is
      infusion of low-dose dopamine. Combination diuretics may effectively increase
      urine output, with the addition of thiazide or spironolactone. Documentation of
      the clinical benefit of ACE inhibitors represents the most important advance in
      therapeutics for CHF in the last decade. ACE inhibitors improves left ventricular
      function, and survival and unless contraindicated, patients with left ventricular
      systolic dysfunction should receive high dose ACE inhibitor with diuretic if
      there is peripheral oedema. For patients who cannot take an ACE inhibitor the
      combination of hydralazine and nitrates may offer some prognostic benefit.
      Digoxin has been the traditional first drug of choice for CHF, but with
      protracted controversy about its efficacy and safety. It is hope that new agents
      as vesnarione, and ibopamine may improve contractility without having adverse
      consequences. Acceptance of beta-blockade as a potentially beneficial therapeutic
      intervention increase in the past year. This year, improved diastolic function
      and afterload reduction were reported with beta-blockade. Amiodarone unlike other
      antiarrhythmic drugs does not seem depress left ventricular function, and may be
      the best drug in patients with CHF and symptomatic arrhythmias. The correct role
      of anticoagulation in patients with CHF remains controversial. Although the
      benefits of anticoagulation for the treatment of most patients with atrial
      fibrillation are increasingly accepted, it has not been shown to improve outcome
      in patients with CHF in normal sinus rhythm.

PMID- 8754363
TI  - [Selected aspects of organ transplantation].
AB  - Problems of replacement therapy with special attention (regards) to renal
      transplantation and selected aspects of other organ transplantation were
      presented. Introduced during the lecture information was updated based on
      enclosed literature.

PMID- 8754364
TI  - [Prevalence of malignant neoplasms in the Tarnow region in the years 1976-1992].
AB  - In the paper the prevalence and kinds of neoplasms in Tarnow region in the years
      1976-1992 was presented. An increase in mortality, particularly in men, probably
      connected with the influence of carcinogenic environmental factors, especially
      smoking cigarettes, was observed. The most frequent malignant neoplasm in men was
      lung cancer whereas in women-breast cancer. An assessment of occurrence of
      malignant neoplasms in various part of Tarnow region was performed. In comparison
      with all Polish population as well as a majority of other regions' population,
      the Tarnow region is characterised by a little lower incidence of malignant
      neoplasms.

PMID- 8754365
TI  - [The most frequent contact allergens in the province of Tarnow].
AB  - 2492 persons presenting contact eczema symptoms were tested with the 22 standard
      allergens' set in the Allergologic Laboratory of the District Hospital in Tarnow
      between 1982 and 1991. 946 persons (38% of all examined patients) had positive
      patch tests. Chromium, nickel, balsam of Peru, cobalt, prodermin,
      paraphenylenodiamine, anasthesin were the most often sensitizing contact
      allergens. The most frequent allergen for women was nickel, for men-chrome. The
      monovalent contact allergy prevailed over the polyvalent one.

PMID- 8754366
TI  - [Methanol poisoning in the Tarnow region in the years 1982-1992].
AB  - In the paper five cases of methanol poisoning in Tarnow region treated with
      hemodialysis are presented and discussed. Despite a high dose of ingested alcohol
      and high levels of blood methanol concentrations and severe metabolic acidosis
      all treated patients survived and fully recovered.

PMID- 8754367
TI  - [Acute ethylene glycol poisoning in the Tarnow region in the years 1982-1993].
AB  - The paper presents 15 causes of severe ethylene glycol poisoning in Tarnow region
      in the years 1982-1993. In the treatment haemodialyses as well as acidosis
      balancing and aethanol administration as an antidotum were preferred. Acute renal
      failure was observed in 73% of poisoned patients and mortality rate was 53%. The
      causes of treatment failure were: high ingested poison dose, too long time
      between poisoning and administration to hospital (and introduction of an
      appropriate treatment), critical clinical condition and severe metabolic
      acidosis.

PMID- 8754368
TI  - [Usefulness of immunologic and protein determinations for assessment of exposure
      to mercury].
AB  - The count of lymphocytes, lymphocytes T (CD 3+), lymphocytes T-helper (CD 4+), T
      suppressor (CD 8+) and NK-cells (CD 16+) as well as immunoglobulins A, D, G, M,
      complements C3c and C4, alpha 1-acid glycoprotein, haptoglobin, ceruloplasmin and
      transferrin were detected in males exposed to mercury vapours and in males of the
      control groups. The shift time weight average (TWA) of mercury in ambient air was
      0,028 mg x m-3. Mean mercury concentration was from 0 to 240 micrograms x 1(-1)
      in urine of the study group and from 0-30 micrograms x 1(-1) in blood.
      Stimulation of lymphocytes system, manifested by an increase number of
      lymphocytes T, T-helper and T-suppressor in the peripheral blood was observed.
      Higher increase of T-suppressor cells than T-helper populations was the case of
      decreased value of the T-helper/T-suppressor ratio by 20.5% (p < 0.05) in workers
      exposed below 10 or by 21% (p < 0.05) in workers exposed over 10 years. Decrease
      of immunoglobulin A, G and M concentration in serum of workers exposed to mercury
      vapours over 20 years was also observed. The concentrations of IgG, C3c, C4 and
      determined acute phase proteins in serum of exposed subjects did not differ from
      that in the non-exposed subjects.

PMID- 8754369
TI  - [Occupational dermatoses in the region of Tarnow in the years 1979-1994].
AB  - An analysis of the occupational diseases diagnosed in years 1979-1994 in the
      region of Tarnow revealed insignificant participation of skin diseases in the
      general number of occupational diseases. The resolute advantage of eczema over
      other skin diseases among the occupational dermatoses has been ascertain. These
      diseases appear most often in the workers of architecture, metal, machine and
      rubber industry as well as in health service. The most frequent cause of the
      allergic occupational eczema was the metal, epoxy resin and rubber components
      contact allergy. Polyvalent allergy predominated the monovalent one. This is
      caused by late occupational skin diseases recognition.

PMID- 8754370
TI  - [Concentration of thyroxine, triiodothyronine and thyrotropin in blood serum of
      children with goitre living in the region of Debica].
AB  - The denotation of the concentration of the thyroxine, triiodothyronine and
      thyrotropin in the serum of the blood provides a accurate examination of the
      functioning of the gland. The number of 294 children at the ages from six to
      fifteen living in Debica and the surrounding area were examined. The control
      group consisted of 123 children (of the same age) without goitres. The
      concentration of the thyroid hormones and thyrotropin in the serum were
      determined. The blood cell count, the level of cholesterol, sugar, iron and the
      elecrophoretic decomposition of proteins were examined. Additionally the
      concentration of iodine in drinking water was determined in 10 randomly chosen
      towns of the region. The children with goitres were taller but their weight did
      not differ from those from the control group. The degree of concentration of
      thyroid hormones agreed with the norms, but the children with goitres had a lower
      level of concentration of thyroxine and higher values of triiodothyronine and
      thyrotropin. The children with goitres had lower values of hemoglobin and sugar.

PMID- 8754371
TI  - [Clinical use of magnesium].
AB  - The next matter under discussion is magnesium. It has the greatest meaning in
      metabolism. The magnesium activates more than 300 enzymes and takes part in
      almost all functions of cellular life. Shortage of magnesium shows almost 100% of
      our population. Supplementation improves treatment of patients and prevents many
      diseases- first of all: circulatory system and nervous system, and in many cases
      absolutely prolongations life time.

PMID- 8754372
TI  - [Prevalence of hepatitis B and C infection and HIV infection in blood donors and
      patients from the internal diseases ward].
AB  - In the paper assessment of a prevalence of hepatitis B and C viruses infections
      as well as HIV infections in potential blood donors and patients from internal
      disease ward in Debica was performed. In none of tested individuals from the
      group of blood donors and patients from the internal disease ward a presence of
      HIV was found. AntiHCV serum antibodies were identified in 2% of patients being
      hospitalized in the internal disease ward. Positive HBs antigen was found in
      serum of one potential blood donor and 3 hospitalized patients that makes 0,94%
      and 3%, respectively, whereas positive antiHBc serum antibodies were identified
      in 12 (12%O patients from internal disease ward.

PMID- 8754373
TI  - [Idiopathic thrombocytopenic purpura in children hospitalized in the children's
      ward of the Regional Hospital in Dabrowa Tarnowska in the years 1984-1994].
AB  - The diagnostic procedures and therapeutic management of idiopathic
      thrombocytopenic purpura in children require that the practising physician should
      make a decision about performing the bone marrow examination and administration
      of steroids or immunoglobulins at the time of disease recognition. In the paper
      controversies on that subject found in the literature are presented as well as an
      analysis is made of the clinical picture, diagnostics and treatment in children
      suffering from ITP hospitalized on the children's ward of the Regional Hospital
      in Dabrowa Tarnowska in the years 1984-1994. Many authors believe that on account
      of considerable percentage of spontaneous recoveries, except restriction of the
      child's activity no medication is necessary. Other think that theoretical
      circumstances of the corticoids and immunoglobulins action mechanism justify
      administration of these preparations with the aim of preventing internal
      bleedings. In the studied matter it has been shown that, as a rule, all
      hospitalized children are given steroids or immunoglobulins, which may result
      from selection of the heaviest cases.

PMID- 8754374
TI  - [Isoptin SR-240 and SR-120 in ambulatory treatment of arterial hypertension].
AB  - Arterial hypertension, especially when co-exists with ischemic heart disease,
      makes an important clinical and social problem. Necessity to continue a treatment
      during the whole patients life produces many problems for a patient himself as
      well as for a physician. Thus, for many years, researches have been carried out
      to find a medicine that would allow to fully control blood pressure for all day,
      would have minimal side-effects and could be administered once a day. Beside
      convertase inhibitors such as Prestarium and Gopten, calcium channel blockers,
      especially retard verapamil forms like Isoptin SR-240 and SR-120 seem to be the
      most appropriate medicines, especially when hypertension is accompanied by
      ischemic heart disease and dysrrythmias. The study was performed in 150
      hypertensive patients who were administered Isoptin SR-240 once a day and Isoptin
      SR-120 twice a day. That dose was sufficient to normalize benign and mild
      hypertension in most patients. Decreased frequency of dyshrrytmias and chest pain
      relief were also observed. Trials to increase daily dose up to 360 mg were
      accompanied by evident side effects such as dizziness and constipations. Much
      more profitable was to join lower Isoptin dose with convertase inhibitors and
      diuretics.

PMID- 8754376
TI  - [Early diagnosis as a condition for conservative treatment of tubal pregnancy
      with methotrexate].
AB  - 27 women with diagnosed unruptured tubal pregnancy were treated using
      methotrexate given intravenous. Three patients failed medical therapy and
      required surgical treatment for tubal rupture. The method was effective in 88,89%
      of cases. 17 women (63%) were given only one dose of methotrexate, ten others
      required 2-4 doses. Using the diagnostic algorithm (endovaginal sonography,
      serial B-hCG determinations and uterine curettage) the presence of an ectopic
      pregnancy was confirmed. The early and relatively easy to follow diagnosis
      allowing an increase in the proportion of patients who could undergo the
      alternative of methotrexate therapy and avoidance of laparotomy. The side effects
      of therapy were mild and transient. Because rupture of ectopic pregnancy can
      occur despite low and declining B-hCG levels, efficient monitoring was performed.

PMID- 8754375
TI  - [Subarachnoid hemorrhage in patients hospitalized in 1990-1993 on the Internal
      Diseases Ward of the hospital in Dabrowa Tarnowska].
AB  - The study was performed in 524 patients who were treated for cerebral stroke on
      the internal Diseases Ward of the Hospital in Dabrowa Tarnowska in the years 1990
      1993. In the analysed group the diagnosis of cerebral infarction was established
      in 428 persons, cerebral hemorrhage in 58 and in 38 patients subarachnoid
      hemorrhage. 24 patients (16 women and 8 men) with subarachnoid hemorrhage were
      transferred for neurosurgical treatment.

PMID- 8754377
TI  - [Preparation for delivery in patients with missed labor considering low-dose
      heparin and prostaglandins].
AB  - No complications were reported in the group of 71 missed labour patients who were
      previously administrated Fraxiparin, antibiotic, Metronidazole and prostaglandins
      as delivery preparation. The following complications were reported in the control
      group of 72 patients: blood loss 500-600 ml without coagulopathy-2 (2.8%), shock
      caused by coagulopathy-2 (2.8%), outcome-1 (1.4%), pelvic inflammatory disease
      (PID)-2 (2,8%). After delivery hematocrit value, red blood cells count, platelets
      count and fibrinogen value were significantly lower, activated partial
      thromboplastic time (APTT) and prothrombin time (PT) were significantly longer in
      control patients in comparison with the group who were given prophylaxis.

PMID- 8754378
TI  - [Pathogenesis and pathologic anatomy of degenerative knee joint disease].
AB  - Etiopathogenesis of degenerative disease of knee joint has been presented in this
      work. The role of instability of the joint, disturbances of biochemical processes
      of cartilage, synovial membrane or joint fluid and microinjuries in pathogenesis
      of this disease has been discussed as well.

PMID- 8754379
TI  - [Clinical, radiologic and other examinations in diagnosis of knee joint changes].
AB  - In this work, a review of diagnostic methods of disease changes in the area of
      knee joint, has been presented. The important role of interview, clinical
      examination, diagnostic arthroscopy or non invasive methods of visualisation such
      as computer tomography and magnetic resonance has been emphasized as well.

PMID- 8754380
TI  - [Conservative treatment of degenerative changes in the knee joint].
AB  - The theory on pain pathogenesis in degenerative changes of knee joints has been
      discussed here as well as the response mechanism to anti-inflammatory non steroid
      drugs. The special attention has been paid to the role of rehabilitation in
      gonarthrosis treatment.

PMID- 8754381
TI  - [Acute pancreatitis as a distant complication of partial gastrectomy by the
      Billroth II method].
AB  - The paper presents a patient with acute pancreatitis (AP) after partial
      gastrectomy by means of Billroth mode. AP was caused by the occlusion of the
      intestinal afferent loop and the secondary pancreatic duct retention. The
      occlusion resulted from gastrointestinal anastomosis performed arterior to the
      transverse colon and adhesion.

PMID- 8754382
TI  - [Late complications after ethylene glycol poisoning--case history].
AB  - Late complications after ethylene glycol intoxication in a 39 years old patient
      were presented. Irreversible severe renal failure and persistent symptoms of
      peripheral nerve system damage dominated in the clinical manifestation.

PMID- 8754383
TI  - [Autosomal dominant polycystic kidney disease in a large family].
AB  - The diagnosis of autosomal dominant polycystic kidney disease (ADPKD) was
      established in persons (6 adult and 8 children) among 34 members of a three
      generations family. The presence of coexisting cysts in liver was ascertained in
      3 women, and the presence of ovarian cysts was discovered in a 14 years old girl.
      Arterial hypertension was observed in 2 men and 2 women. The symptoms of
      initiating renal failure were found in 1 patient. The clinical observation of the
      most numerous among described in accessible literature family will be continued.

PMID- 8754384
TI  - [Myocardial infarction in a man with Wolff-Parkinson-White syndrome].
AB  - A case of 52 years old male patient with antero-septal myocardial infarction in
      the course of type B Wolff-Parkinson-White syndrome has been described.
      Intravenous administration of 50 mg of ajmaline 2 hours after admission to
      hospital suppressed the electrocardiographic signs of preexcitation and disclosed
      previously imperceptible image of acute inferior myocardial infarction. Repeated
      intravenous ajmaline injection before discharging from the hospital enabled to
      specify the final localisation of the infarction (antero-septal and inferior),
      made possible the realization of ecg exercise test and ventricular late
      potentials analysis (no late potentials were detected). The clinical course of
      the disease was complicated by the left ventricular failure, which was brought in
      check without digitalis administration. The outpatient follow-up is carried out
      after the health resort treatment and the patient is in good conditions 6 months
      after his discharge from the hospital. There is no such a case found in the
      available literature.

PMID- 8754385
TI  - [A case of bilateral temporal arteritis].
AB  - The authors have presented a case of bilateral temporal arteritis (giant cell
      arteritis) of a female patient taken to a hospital because of a sudden blindness
      of her left eye. At first, the retinal embolism has been diagnosed, but after a
      sudden worsening of the general condition of the patient and the diagnosis of the
      retinal embolism of the other eye and results of biochemical investigation tests
      the previous diagnosis has been changed to: bilateral temporal arteritis.

PMID- 8754386
TI  - [A happy ending in the case of a careless pregnant woman after kidney
      transplantation].
AB  - A successful delivery of a woman after kidney transplantation who had completely
      neglected prenatal care is described. PGE2 anal suppository was successfully
      administered during the delivery to make the cervix more susceptible. Problems
      connected with pregnancy after kidney transplant are discussed. Psychological
      consultation should be included in perinatal care.

PMID- 8754387
TI  - [Pregnancy and labor in a pregnant woman with nephrocalcinosis complicated by
      renal failure].
AB  - The paper presents a case of woman with nephrocalcinosis confirmed 10 years ago.
      During her third pregnancy a renal failure occurred with increasing urinary
      retention in the right kidney. Conservative treatment was applied without
      dialysis, despite of renal biochemical parameters, which balanced on the edge of
      the indication for this procedure. The pregnancy was managed by the 32-nd week
      and then cesarean section was performed because of increasing levels of
      creatinine and urea in the serum and enlargement of hydronephrosis. After the
      delivery a recovery of renal function was observed. Patient was discharged in
      good general condition on 9-th day after cesarean section and baby after 52 days
      of hospitalization in neonatal department when she has reached weight of 3000 g.

PMID- 8754388
TI  - [Change of serum amyloid P component concentrations in women].
AB  - Serum amyloid P component (SAP) is a glycoprotein which was shown to be deposited
      in periarterial tissues and the glomerular basement membrane. It plays a part in
      aging, and the onset of amyloidosis and Alzheimer's disease. In order to
      investigate the effects of sex steroids on the SAP level in menopausal women, SAP
      was purified. Anti-SAP was raised through the immunization of rabbits. The SAP
      level was assayed by micro single radial immunodiffusion. The SAP levels
      increased with aging from 1.1 +/- 0.8mg/dl (mean +/- S.D.) to 5.08 +/- 1.31mg/dl
      in women. And the SAP level in males was significantly higher in the 15 to 50
      year age group than in females of similar ages (p < 0.001). And in the menstrual
      cycle, the SAP concentrations were significantly higher in the menstrual period
      (p < 0.05). During hormonal therapy in climacteric women, the SAP levels
      decreased significantly (p < 0.001) after Premarin treatment (from 5.66 +/-
      1.45mg/dl to 4.15 +/- 0.94 mg/dl) and increased (p < 0.001) after
      dehydroepiandrosterone therapy (from 4.00 +/- 0.74mg/dl to 6.07 +/- 1.14mg/dl).
      From these findings, the SAP levels in human were concluded to be age dependently
      increased, and higher in the menstrual period. And it is suggested that a sex
      difference in SAP is concerned with the effect of estrogen fluctuation.

PMID- 8754389
TI  - [Effect of prolonged intravenous ritodrine tocolysis on diurnal glucose profiles
      in pregnant women with normal carbohydrate tolerance].
AB  - Our purpose was to investigate an effect of prolonged intravenous ritodrine
      tocolysis on maternal carbohydrate metabolism in women with normal glucose
      tolerance. In patients with preterm labor, diurnal plasma glucose levels were
      measured both during the 24 hours after beginning the therapy (phase 1) and each
      day during over five days of continuous ritodrine tocolysis (phase 2). We also
      measured diurnal plasma glucose levels in normal pregnant women without any
      therapy (control group). In phase 1, in comparison with before therapy, a
      significant increase in the plasma glucose levels was observed with the highest
      level at 9 hours after starting ritodrine (146.4 +/- 31.6mg/dl). The higher
      plasma glucose levels persisted during phase 1. Although infusion rates were
      similar in both phases, maternal plasma glucose levels in phase 1 were
      significantly higher than in phase 2 (mean plasma glucose level, 128.1 +/-
      21.3mg/dl vs. 92.7 +/- 11.6 mg/dl, p < 0.05; maximum plasma glucose level, 159.5
      +/- 25.2mg/dl vs. 106.6 +/- 14.5mg/dl, p < 0.05). Diurnal glucose levels in phase
      2 were similar to those in the control group. In phase 1, there seemed to be a
      dose-dependent relation between the ritodrine infusion rates and plasma glucose
      levels, but we did not find any relationship between them in phase 2. In
      conclusion, although hyperglycemia occurs during the initial phase of continuous
      ritodrine therapy (at least 24 hours), prolonged ritodrine infusion leads to
      normalization of the maternal plasma glucose levels.

PMID- 8754390
TI  - [Study on anaerobic threshold in normal pregnant women].
AB  - We evaluated the anaerobic threshold (AT) in 104 normal pregnant women mainly in
      their second trimester. Each exercise testing was performed by using incremental
      bicycle ergometry at a pedal frequency of 60rpm while monitoring maternal heart
      rate, maternal blood pressure, minute ventilation (VE),oxygen uptake (VO2) and
      carbon dioxide output (VCO2) every 30 seconds. The AT was determined by
      estimating the point of departure from linearity of the plot of VE as a function
      of VO2. We could determine the AT in 100 cases (96.2%), and their AT values and
      the heart rates at AT point were 14.7 +/- 1.7ml/min/kg (mean +/- S.D.) and 128 +/
      12bpm, respectively. AT decreased significantly (p < 0.01) with the length of
      gestation, because of increased maternal body weight. The heart rate at the AT
      also declined significantly (p < 0.05) with gestational age, but it had no
      relation with maternal body weight. These results show that the maternal heart
      rate becomes hard to increase with gestational age, so that the maximal heart
      rate, as an index of exercise intensity during exercise should decrease with
      advancing gestational age.

PMID- 8754391
TI  - [Electron microscopic histochemical studies on the localization of hyaluronic
      acid in Wharton's jelly of the human umbilical cord].
AB  - The mode and distribution of hyaluronic acid in Wharton's jelly of the human
      umbilical cord was studied by the electron microscopic histochemical technique.
      By means of ruthenium red (RR) staining, RR-positive material was observed as
      granules approximately 30nm in diameter in the fibroblast of Wharton's jelly.
      Around the fibroblast, it was observed as fibril structures on the cell surface
      or as granules approximately 13nm in diameter in the basement membrane-like
      structure around the cell. In the extracellular matrix, it was observed as
      granules or amorphous materials on collagen fibrils. Only the 30nm granules in RR
      positive structures disappeared due to amylase digestion. The other structures
      were digested by Streptomyces hyaluronidase. On the basis of the above findings,
      it was concluded that hyaluronic acid is formed as hydrated gel around the
      fibroblast and collagen fibrils in Wharton's jelly of the human umbilical cord.
      These results suggest that its structure is one of the factors in maintaining the
      elastic aptitude of the umbilical cord, to protect from any pressure, such as
      fetal movement, etc., in the uterine cavity.

PMID- 8754392
TI  - [An analysis of pelvic and para-aortic lymph node metastasis in ovarian carcinoma
      by systematic retroperitoneal lymph node dissection].
AB  - We performed a systematic retroperitoneal lymph node dissection (RPLND) on 137
      patients with primary ovarian carcinoma, of whom 97 had undergone RPLND during
      the primary surgery before chemotherapy and 40 had undergone RPLND during the
      secondary cytoreductive surgery after preoperative chemotherapy. The tentative
      staging of the ovarian carcinoma used in this study was determined according to
      the FIGO criteria without considering the pathologic findings of retroperitoneal
      lymph nodes. Nodal metastasis was seen in 21.9% (30/137) of them. Thirteen had
      positive pelvic lymph nodes (PLN) but no positive para-aortic nodes (PAN). Eleven
      had both positive PLN and positive PAN. Six had positive PAN but no positive PLN.
      The PAN was the most frequent site of metastasis (17/137). Next were the common
      iliac, obturator, and lateral group of deep inguinal nodes. Solitary metastasis
      in the patients who had undergone RPLND during the primary surgery was seen in a
      PAN and a common iliac node. Among 24 patients with PLN metastasis, there was a
      significant (p < 0.05) difference in the number of positive PLN between the
      patients with PAN metastasis (5.27 +/- 3.00) and the patients without PAN
      metastasis (2.62 +/- 1.66). These results indicate that the PAN and common iliac
      nodes are the most important site of nodal metastasis in ovarian carcinoma. The
      metastasis to PLN such as obturator node and internal iliac node seems to occur
      independently of the PAN metastasis, and the PAN metastasis occurs not only
      through the direct route but also as a consequence of extension of PLN
      metastases. Systematic retroperitoneal lymph node exploration therefore seems to
      be necessary to clarify the lymph node status.

PMID- 8754393
TI  - [The expression of c-myc protein in uterine cervical cancer: a possible
      prognostic indicator].
AB  - Forty-eight cases of human uterine cervical cancer were examined for the
      expression of c-myc protein by immunohistochemical staining. The overexpression
      of c-myc was detected in 17 of 48 cases (35%), which is consistent with previous
      reports. The frequency of c-myc overexpression was not associated with the
      clinical stage. Relapse was observed in 7 of 15 cases (47%) which had
      overexpression of c-myc (mean follow-up period: 35 months), whereas relapse was
      observed in only 3 of 30 cases (10%) which did not overexpress c-myc (mean follow
      up period: 33 months). The five-year survival rate was significantly lower in the
      cases overexpressing c-myc than in those not overexpressing it. This indicates
      that the overexpression of c-myc may be associated with a high risk of relapse
      and poor prognosis. We also analysed the correlation between lymph node
      metastasis, cervical stromal invasion and c-myc overexpression, and did not find
      any correlation between them. These results suggest that the overexpression of c
      myc in cervical cancer may be a prognostic indicator for predictive testing.

PMID- 8754394
TI  - [An immunohistological study on expression of glutathione S-transferase pi (form)
      in dysplastic and neoplastic human uterine cervix lesions].
AB  - The glutathione S-transferase (GST) pi has been studied in association with the
      mechanisms of multidrug resistance and as a marker for malignant tumors. In this
      study, specimens from 92 cases of cervical neoplasms and 10 cases of normal
      squamous epithelium adhering to myoma were stained immunohistochemically with a
      rabbit polyclonal antibody to GST-pi. In 6 cases of normal squamous epithelium,
      the intermediate layer was positively stained with the GST-pi antibody. In all 20
      cases of dysplasia, the cells with koilocytotic atypia were stained positively.
      In all 10 cases of carcinoma in situ and all 16 cases of stage Ia squamous cell
      carcinoma, various intensities of GST-pi staining were demonstrated. Forty-six
      specimens of stage Ib or more squamous cell carcinoma were positive for GST-pi
      binding except only one case. In general, squamous cell carcinoma of the uterine
      cervix is resistant to chemotherapeutic agents. GST-pi is most frequently stained
      in cervical squamous cell carcinoma as compared with ovarian or endometrial
      carcinoma. In conclusion, these results suggest that GST-pi may be a marker for
      cervical squamous cell carcinoma.

PMID- 8754395
TI  - [Influence of reduction in number of transferred embryos on the rates of total
      and multiple pregnancy].

PMID- 8754396
TI  - [A puerperal woman received massive ABO-incompatible blood transfusion: a case
      report rescued by exchange transfusion therapy].

PMID- 8754397
TI  - [Down syndrome with hyperechoic bowel finding in the second trimester: a case
      report].

PMID- 8754398
TI  - [Evaluation by dynamic MRI of the response of neoadjuvant chemotherapy in uterine
      cervical cancer].

PMID- 8754399
TI  - [Two cases of breast cancer, simultaneously associated with uterine cancer].

PMID- 8754400
TI  - [The effect of long term erythropoietin treatment on levels of free amino acids
      in patients with long term hemodialysis].
AB  - In order to assess the effect of erythropoietin (Epo) treatment on amino acids
      profile in hemodialysis patients (HD pts) 2 groups of pts were analyzed: I-12 pts
      HD for 146 +/- 71 months, Epo treated for 64 +/- 10 months, II-17 pts HD for 120
      +/- 39 months, non Epo treated, mean Hb 11.5 +/- 1.2 g/dl. Controls consisted of
      11 healthy individuals. Amino acids were estimated by HPLC OPA method. In group I
      blood levels of leucine (p < 0.03), valine (p < 0.002) were decreased and alanine
      (p < 0.05) was increased when compared to controls. In this group, blood levels
      of methionine, tyrosine and asparagine were elevated (p < 0.04) when compared to
      group II but they were lower (about 30%) then in controls. In group II pts showed
      reduced levels of valine (p < 0.008), leucine (p < 0.001), methionine (p <
      0.0001), tyrosine (p < 0.003), asparagine (p < 0.04), whereas serine, glutamate
      and alanine (p < 0.04) were increased when compared to controls. Essential to
      nonessential amino acids ratios in group I, II and controls were as follows:
      0.17; 0.12; 0.49 respectively. There were not substantial differences in amino
      acids in pts with elevated or normal PTH level in both HD groups. Long term EPO
      treatment only partially corrected changes in amino acids levels in pts with
      chronic renal failure.

PMID- 8754401
TI  - [Treatment with human recombinant erythropoietin and nutritional status of
      patients on lon term dialysis].
AB  - In order to assess the effect of long term erythropoietin (EPO) therapy on the
      nutritional status of hemodialysed (HD) patients 2 groups of HD patients were
      studied: I-EPO treated for 72 +/- 8 mo, 12 patients, HD for 138 +/- 66 mo, II
      control group, 14 patients with Ht 30%, HD for 121 +/- 35 mo. At the onset and
      after 6 years of follow up patients underwent the following examination: length,
      body weight, body mass index, body fat stores, arm muscle circumference and total
      serum protein, serum albumin, lymphocyte count, creatinine, urea, cholesterol and
      PTH. In EPO group mean BMI, body fat, arm muscle circumference, visceral protein
      and total lymphocyte count were not change. In control group the decrease in
      height, body weight, BMI, body fat stores, arm muscle circumference and albumin
      were observed. Elevation of PTH estimated in half of patients in EPO group and
      75% of patients in control group could influence the nutritional status of
      hemodialysed patients. CONCLUSION: 1. Nutritional status of majority of
      hemodialysed patients was not change during six years EPO therapy. 2. Non EPO
      treated patients showed the decrease of anthropometric measurements and serum
      albumin.

PMID- 8754402
TI  - [Use of urea kinetic modeling for evaluating the efficacy of reusing capillary
      dialyzers].
AB  - The aim of the study was to evaluate the influence of follow fiber dialyzers
      reprocessing procedure on urea kinetic modeling parameters, dialysis
      effectiveness for small molecules and effective clearance/predicted clearance
      ratio. Fifty patients (27 F, 23 M) aged 18-61 years (mean 47) being on
      maintenance hemodialysis due to end stage renal failure for 4-136 months were
      included into the study. Patients were treated 3 times a week with blood flow 160
      290 ml/min and dialysate flow 500 ml/min. The dialysis time was calculated
      individually based on urea kinetic modeling parameters. Reprocessing of dialyzers
      was performed using Renatron RS 8300 and Renalin as sterilized agent. Dialysers
      with ppr below 80% were excluded from the use. Mean values of dialysis index
      Kt/V, TAC and dialysis effectiveness (Ct/C0) for urea, creatinine, uric acid and
      kalium as well as values of effective/predicted clearance ratio for consecutive
      reprocessing procedures were compared with the results obtained for the new
      dialyzers. There was no significant influence of reprocessing procedure on Kt/V,
      TAC and Ct/C0 for tested substances and studied clearances. The obtained results
      indicates that dialysers reprocessing procedure performed according to the
      described protocol was safe and didn't decrease dialysis effectiveness.

PMID- 8754403
TI  - [Peritoneal blood flow and peritoneal transfer parameters during intermittent
      peritoneal dialyses performed with administration of sodium nitroprusside or
      chlorpromazine].
AB  - Effective peritoneal capillary blood flow (EPBF) was evaluated by calculation of
      diffusive mass transport coefficient of CO2 during intermittent peritoneal
      dialysis performed with intraperitoneal administration of sodium nitroprusside
      (NP, 5 mg/l of dialysis solution) or chlorpromazine (Cl-Prom, 2.5 mg/l of
      dialysis solution). Peritoneal transfer rates of substances of different
      molecular size and charge were simultaneously examined and compared with EPBF.
      During NP or Cl-Prom administration, EPBF was respectively 220 +/- 40 (n = 11)
      and 224 +/- 29 (n = 10) ml/min. These values were insignificantly higher than
      those obtained during dialyses without drugs (169 +/- 16 ml/min, n = 10). NP and
      Cl-Prom did not cause any significant changes in peritoneal transfer of CO2.
      Transfer rates of HCO3 and tCO2 were increased only with NP. Both drugs enhanced
      peritoneal removal of Na+, K+, urea, uric acid and total protein, but with
      similar EPBF during the use of both drugs, the effect of NP was more pronounced.
      The obtained results indicate that EPBF is not a major factor responsible for
      enhanced peritoneal transfer rates during dialyses performed with NP or Cl-Prom.

PMID- 8754404
TI  - [Prevalence of response to anti-HBV infection in patients on maintenance
      hemodialysis infected with hepatitis C virus (HCV)].
AB  - We have studied the antibody response to hepatitis B vaccine in 42 hemodialysis
      patients; 8 of them were diagnosed as having HCV infection before vaccination.
      Hemodialysis patients received four doses of recombinant HB vaccine (Engerix-B,
      SKB, 40 micrograms per dose). Seroconversion occurred in 71.4% of all
      hemodialysis patients; in 79.4% of HCV-negative and in 37.5% of HCV-positive
      patients. Effective immunity (anti-HBs titer higher than 100 m IU/ml) was
      observed in 12.5% of HCV positive and in 35.3% of HCV-negative patients. We
      conclude that HCV infection may modify or postpone the response to hepatitis B
      vaccine.

PMID- 8754405
TI  - [Prolongation of allogenic rat renal graft survival after perfusion the organ
      with anti-MHC class II antibody].
AB  - One of the main factor inducing rejection of the allogenic graft are the donor
      MHC-class II antigens. The cytotoxic damage or the elimination of these cells
      from the organ may influence his function after grafting. In this study, the
      influence of the continuous perfusion of the rat kidney with monoclonal antibody
      against rat MHC-class II antigens (MoAb 25D5) on graft survivals was
      investigated. For the perfusion, the HTK solution containing MoAb 25D5, rat
      complement (C) and Pentoxifilline (Ptx) was used. After one-hour perfusion at 21
      degrees C kidney were transplanted to the syngenic (LEW-LEW) or allogenic (Da
      LEW) recipients, kidney perfused with the solution containing MoAb 25D5 and C
      survived statistically longer (14.0 +/- 2.4 days) than in the control group
      without perfusion (7.7 +/- 0.5 days) or after perfusion with the solution
      containing only Ptx (7.8 +/- 0.8 days). It seems likely that the continuous
      perfusion of the rat kidney with HTK protective solution containing MoAb against
      MHC-class II antigens and C can reduce the immunogenicity of the graft.

PMID- 8754406
TI  - [Content of thiamin in plasma and erythrocytes in patients with end stage renal
      disease].
AB  - In 68 patients with end stage renal disease (ESRD), nondialyzed-(ND)-21 treated
      by hemodialysis (HD)-27 or intermittent peritoneal dialysis (IPD)8 and continuous
      ambulatory peritoneal dialysis (CAPD)-12, we examined thiamine free (Th F) and
      thiamine total (Th T) content in plasma (P) and erythrocytes (E). 20 healthy
      volunteers (HV) served as a control group. Thiamine content in plasma and in
      hemolysate was assessed by fluorimetric method according to Blum and Merkel. In
      all patients the mean Th FP, Th TP, and Th FE, Th TE levels were decreased in
      comparison to HV. Mean level of Th FE in ND and IPD was significantly decreased
      (p < 0.05) in comparison to Th FE to HV and to patients treated by HD or CAPD.
      Mean level of Th FP was the lowest in IPD group, but did not differ significantly
      from Th FP in ND, HD and CAPD). In IPD patients mean level of Th TE was the
      lowest and differed significantly (p < 0.05) from that in HD and CAPD groups. The
      lowest mean level of Th TP we found in CAPD patients. There was significant
      difference with it in ND and HV group (p). Patients treated by HD and CAPD
      presented almost normal levels of Th FE and Th TE. The highest mean levels of Th
      FP and Th TP were found in ND patients. We suggest the need of thiamine
      supplementation in ESRD patients especially in those treated by dialysis. The
      supplementation of thiamine is needed particularly in patients on peritoneal
      dialysis.

PMID- 8754407
TI  - [Oral calcitriol pulse therapy in treatment of secondary hyperparathyroidism in
      patients with long term hemodialysis].
AB  - Oral calcitriol pulse therapy slowly becomes a method of choice in the treatment
      of secondary hyperparathyroidism in hemodialysis patients. It appears to be
      equally effective and simultaneously significantly cheaper than an intravenous
      therapy. In last year we have applied such a treatment to 12 hemodialysis
      patients with severe secondary hyperparathyroidism (iPTH range: 447-1228 pg/ml).
      All of them were hemodialysed 3 times a week with dialysate Ca+2 level 1.25-1.75
      mM/l. Calcium carbonate was administered to maintain serum Ca level between 9.0
      11.0 mg/dl and phosphate below 6.0 mg/dl. The patients were given calcitriol at
      dose 0.1 microgram/kg once a week, but it was obligatory to take a drug at
      bedtime, at least two hours after the last meal, a day before hemodialysis.
      During the treatment we divided the patients into two groups: I-patients who
      responded to our treatment (7/12); II-treatment was unsuccessful (5/12). In this
      group we decided to increase the dose of calcitriol to 0.075 micrograms/kg twice
      a week after 6 months use of a previous one. We have achieved statistically
      significant decrease of parathormone (p < 0.001) and alkaline phosphatase (p <
      0.02) in group I and after the increase the dose of calcitriol there occurred the
      decrease of parathormone (p < 0.05) and alkaline phosphatase (p < 0.002) in group
      II. Simultaneously we have observed a great clinical improvement. Our results
      confirm the fact that even severe secondary hyperparathyroidism can be
      successfully treated with oral calcitriol pulse therapy. Administering of high
      doses of calcitriol at bedtime increases safety of this procedure-we have not
      observed any case of hypercalcemia.

PMID- 8754408
TI  - [Evaluation of platelet membrane structure in patients with chronic
      glomerulonephritis (CGN)].
AB  - The structure of platelet membrane determines platelet surface glycoprotein
      receptors and correct cell function. Meanwhile different diseases and drugs may
      induce changes in this structure. The aim of this study was to determine
      structure of platelet lipid bilayer in patients with chronic glomerulonephritis
      (CGN) in comparison to control group. Studies were carried out in 30 patients
      with nephrotic syndrome (NS) and 30 patients without this syndrome and 15
      controls. Electron spin resonance phenomenon with spin labelling, was used for
      estimation of platelet membrane structure. CGN patient platelets showed lower
      order parameter A/C and increased rotation correlation time tau in comparison
      with healthy subjects. It indicated abnormal platelet membrane structure in these
      patients. The negative significant correlation between parameter A/C and plasma
      fibrinogen concentration of NS patients has been found (r = -0.5; p < 0.05).
      Additionally the value of an order parameter (A/C) has significantly positively
      correlated with serum triglycerides concentration in patients with NS and
      spontaneous platelet aggregation (r = 0.52, p < 0.05). Conclusion. 1. CGN patient
      platelets have revealed disorders of lipid bilayer structure. 2. These disorders
      could be responsible for decreased platelet aggregation observed in CGN patients
      in comparison to healthy controls.

PMID- 8754409
TI  - [Evaluation of factors influencing platelet aggregation in patients with chronic
      glomerulonephritis (CGN)].
AB  - Platelets (PLT) play an important role in hemostasis, modulation of immunological
      and inflammatory processes. There is also evidence that PLT takes part in the
      development of atherosclerosis and glomerulosclerosis. The aim of presented study
      was to determine morphological and functional changes of platelets and their
      relation to the lipid, protein and coagulation factors disturbances in patients
      with chronic glomerulonephritis (CGN). The studies were carried out in 60
      patients with CGN diagnosed by renal biopsy: 30 patients without nephrotic
      syndrome (NS)-CGN and 30 patients with NS-CGN+NS. Protein and lipid disturbances,
      coagulation factors were estimated using routine laboratory methods. Platelet
      count (PLT), mean platelet volume (MPV) and modal platelet volume (PLT-Mode) were
      measured using Technicon H1 hematological autoanalyser. Platelet function was
      assessed by aggregometry using turbidimetric method (inductors: ADP 1-3 microM,
      collagen 50g/ml, epinephrine 0.25-5 microM). Spontaneous platelet aggregation
      (SPA) was measured in platelet rich plasma (PRP) without inductors for 15 min, in
      1-2 hours after venesection. SPA was observed in 9 of 30 patients with CGN and in
      19 of 30 patients with CGN+NS. MPV and PLT Mode were significantly higher in
      patient showing SPA compared with those without. Significant correlations between
      SPA and the concentration of plasma albumin (r = -0,70; p < 0.02) TG and CH-LDL
      (r = 0,61; p < 0.05) were found in CGN+NS patients. APTT was significantly
      shorter in patients showing SPA compared with those without and negative
      significant correlation between SPA and APTT was found. Platelet aggregation to
      inductors in CGN and CGN+NS patients was diminished compared with control group.
      Lack of second phase aggregation in response to aggregation inducers was observed
      in patients with SPA. Conclusions. 1. Platelet hyperaggregation play an important
      role in hypercoagulation state in CGN patients. 2. SPA in vitro was observed in
      majority of CGN+NS patients and in some without NS. 3. Pathomechanism of SPA is
      probably multifactorial (hypoalbuminemia, dyslipidemia, changes in concentration
      of coagulation parameters).

PMID- 8754410
TI  - [The role of dialysis membranes in elimination of uremic toxins].

PMID- 8754411
TI  - [The role of tubulointerstitial changes in progression of kidney function failure
      in patients with chronic glomerulonephritis (GN)].
AB  - In most cases of glomerulonephritis (GN) long-term course lead to chronic renal
      failure. The cause of inevitably gradually progress of GN to end-stage renal
      disease (ESRD) is unclear. The histological abnormalities seen in patients with
      progressive renal failure consist of focal and segmental glomerulosclerosis and
      tubulointerstitial nephritis. At present it is considered that tubulointerstitial
      changes attends almost all forms of progressive glomerular and vascular injury.
      It was known that chronic tubulointerstitial nephritis is characterized
      morphologically by tubular atrophy, interstitial fibrosis and interstitial
      inflammation of variable severity. The pathomechanism of this changes is
      complicated. Tubular ischaemia results from obliteration of peritubular
      capillaries, adaptation of tubular function with increased oxygen consumption and
      increased glomerular capillary permeability to macromolecules are reasons of
      chronic tubular damage. Injured tubules release growth factors and cytokines,
      which induce interstitial fibroblast proliferation, chemo-attraction and
      proliferation of infiltrating cells, and disruption of the balance between
      synthesis and degradation of cellular constituents. The consequences of these
      processes are tubular atrophy and interstitial fibrosis. Because of many studies
      concurred that tubulointerstitial changes determinant the progression of GN,
      tubular injury markers were searched for. Although over 50 enzymes were detected
      in human urine, only a few have been used for diagnosis in renal disease. The
      most widely used are lysosomal enzyme N acetyl-beta-D-glucosaminidase (NAG) and
      brush border enzymes alanine-aminopeptidase (AAP) and gamma-glutamyltransferase
      (GGT). tubular damage in hypertension, diabetes and in diagnostics of renal
      disease. AAP and GGT, brush border enzymes seem to be sensitive markers of renal
      injury too. Pathological value of GGT was observed even in the early stage of
      disease. Measurement of urinary excretion of low molecular weight proteins was
      valuable supplement in estimation of tubulointerstitial system malfunction. These
      proteins are readily filtered by normal glomeruli and virtually completely
      reabsorbed by normal proximal tubules. Favour are alpha-1-microglobulin (alpha-1
      m) and retinol-binding protein (RBP) because they are less affected than beta-2
      microglobulin (beta-2-m) by low urine pH. Above presented review confirm that
      further research in correlation between activity of disease, histological
      picture, deterioration in renal function and changes in urinary excretion of
      markers proteins (for example alpha-1-m, AAP, NAG, GGT) is advisable, and can
      contribute to use in clinic diagnostics of GN.

PMID- 8754412
TI  - [Anticoagulants in hemodialysis therapy].

PMID- 8754413
TI  - [A case of hemolytic-uremic syndrome after normal pregnancy and delivery. Two
      year follow-up observations].
AB  - Hemolytic-uremic syndrome is a very rare complication in the postpartum period,
      starting a few days or few months after usually spontaneous labour, which
      concludes a normal pregnancy. We report a case in which treatment with early
      hemodialysis, heparin, corticoids, and blood transfusions appeared to cure the
      acute hemolytic anaemia and the thrombocytopenia, normalise kidney function and
      prevent kidney damage.

PMID- 8754414
TI  - [Etiology and epidemiology of 547 episodes of acute viral hepatitis diagnosed in
      adults in a general hospital (1983-1994)].
AB  - The etiology and epidemiology of 547 consecutive episodes of acute viral
      hepatitis in adults and diagnosed in a general hospital over 12 years (1983-1994)
      were prospectively analyzed as were the changes observed during the two halves of
      the study period. Of the 547 episodes, 25.4% were of type A, 41.1% type B, 21.9%
      type C, 6.6% non A, non B, non C, 2.4% type D, 1.1% by cytomegalovirus and 1.4%
      by the Epstein-Barr virus. The proportion of hepatitis A increased from 21.5%
      from 1983-1988 to 34.1% from 1989-1994 (p = 0.002), while hepatitis C decreased
      from 24.9% to 15.3% (p = 0.01) during the same periods. The proportion of
      hepatitis B observed in intravenous drug addicts fell from 56.1% in the first
      period to 39.3% in the second period (p = 0.03), while sexually transmitted
      hepatitis B rose from 7.3% to 22.9% (p = 0.002). A decrease was observed in the
      cases of hepatitis C in both periods in the intravenous drug addict cases (60.6%
      vs. 34.6%; p = 0.03) with an increase being observed in the C virus transmitted
      by unapparent mechanisms (2.1% vs. 23.1%; p = 0.001). These results suggest that
      modifications may currently be observed in the epidemiology of the viral
      hepatitis in Spain and that these trends should be taken into account when
      planning preventive strategies.

PMID- 8754415
TI  - [Pyogenic liver abscess. A descriptive study of 35 cases].
AB  - Thirty-five patients with pyogenic hepatic abscess (PHA) attended over 13 years
      in a general hospital were studied. The aim of the study was to know the
      usefulness of the performance of opaque enema in patients with cryptogenic PHA
      and the prognosis of the patients treated with only antibiotics. The most
      frequent clinical and analytical manifestations were fever and leukocytosis.
      Other less frequent findings were abdominal pain, hepatomegaly and elevated
      alkaline phosphatase and aspartate aminotransferase levels. One third of the
      patients presented radiologic alterations at the base of the right hemithorax.
      Colon studies in the patients with cryptogenic PHA performed to discard another
      origin of the abscess demonstrated very low profitability. Abdominal echography
      showed adequate sensitivity (0.85) in the diagnosis of PHA and allowed
      percutaneous drainage to be performed in most of the cases. The patients who were
      treated with only antibiotics presented a significantly worse prognosis than
      those treated with antibiotics and drainage (p = 0.03). Drainage of the PHA also
      allowed a decrease in the length of fever duration.

PMID- 8754417
TI  - [Pleural empyema caused by Cryptococcus neoformans in a patient with liver
      cirrhosis].
AB  - Gram negative infections, particularly by E. coli, are usually observed in
      cirrhotic patients while infections by Cryptococcus neoformans are commonly found
      in immunosuppressed patients. The case of a cirrhotic patient with hepatitis C
      virus infection who developed pleural infection by C. neoformans is presented. No
      disease other than cirrhosis was observed in the patient. The treatment with oral
      fluconazole was initiated with good clinical response and infection cure. The
      efficacy of fluconazole in infections by this microorganism has been reported in
      other cases, mainly in patients with acquired immunodeficiency syndrome. The fact
      that the patient may be a liver transplant candidate, given the hepatic
      cirrhosis, leads to speculation as to the need for chronic treatment with
      fluconazole to avoid reactivation of C. neoformans on initiation of pharmacologic
      immunosuppression.

PMID- 8754416
TI  - [Echoendoscopy: pathological diagnosis using real-time puncture-aspiration].
AB  - The aim of this study was to obtain pathologic diagnosis by aspiration punction
      (AP) by real time lineal echoendoscopy in different lesions suspected to be
      malignant. AP was performed in 6 cases with a Pentax-Hitachi FG 32UA lineal
      echoendoscopy. Four pancreatic neoplasms, one plastic linitis and one adenopathy
      of the celiac trunk were observed. Malignancy was confirmed by clinical evolution
      or surgery. The sensitivity of malignancy diagnosis was 67%, specificity 100% and
      diagnostic certainly 87%. No complications were observed. In the authors'
      preliminary experience, aspiration punction with real time lineal echoendoscopy
      allowed pathological diagnosis to be performed safely and effectively with
      relative simplicity.

PMID- 8754418
TI  - [Hepatitis C following administration of intravenous immunoglobulins].
AB  - Five patients with hepatitis C virus infection of different severity and
      evolution following the administration of intravenous (i.v.) immunoglobulins
      (Igs) are presented. The important morbidity of hepatitis C virus infection and
      the need for adequate donor screening are discussed, as is accurate indication of
      these drugs in the management of patients with immunosuppression and other
      diseases.

PMID- 8754419
TI  - [Chronic calcifying pancreatitis and extracorporeal pancreatic lithotripsy].
AB  - Abdominal pain is the most frequent symptom of chronic pancreatitis and may, on
      occasions, lead to great treatment problems. The case of a 35-years-old patient
      diagnosed with chronic calcifying pancreatitis of enolic etiology who showed
      dilatation of the main pancreatic duct and intracanalicular lithiasis is
      reported. Medical, endoscopic and surgical alternatives failed but fragmentation
      of the lithiasis by extracorporeal lithotripsy was successful.

PMID- 8754420
TI  - [Heterozygotic alpha-1 antitrypsin deficiency. A case report].
AB  - The clinical, analytical (including phenotypical) and histologic (optical and
      ultrastructural) data of a 34-years-old male patient attended for evaluation of
      moderate hypertransaminasemia discovered following a company screening
      examination. The existence of an alpha-1-antitrypsin heterozygotic deficit (MZ)
      was detected with flattening of the alpha wave in the proteinogram and a
      decreased serum level of this glycoprotein. Morpho-pathologically no PAS positive
      globules were optically found on liver biopsy although dilatation of the rough RE
      was observed with deposition in the medium electrodensity material, the
      significance of which is discussed on the basis of the patient's phenotype. It is
      suggested that serum studies of alpha-1-antitrypsin should be included in the
      routine evaluation of chronic liver diseases.

PMID- 8754421
TI  - [Hepatitis C vaccine. Current status].

PMID- 8754422
TI  - [Digestive disease in cystic fibrosis].

PMID- 8754423
TI  - [Autoantibodies in liver diseases: interpretation and pathogenic importance].

PMID- 8754424
TI  - [Hyperthyroidism, hyperferritinemia and change in liver function tests].

PMID- 8754425
TI  - [Acute hepatitis caused by measles virus].

PMID- 8754426
TI  - [Multiple liver abscesses, peritonitis and acute enteritis caused by Klebsiella
      pneumoniae].

PMID- 8754427
TI  - [The virtues of a good endoscopist].

PMID- 8754428
TI  - Victim no more.

PMID- 8754429
TI  - Immunity for reporting child abuse.

PMID- 8754430
TI  - Sexual abuse--the numbers don't fit.

PMID- 8754431
TI  - From expertise to competence....

PMID- 8754432
TI  - Developing time-based protocols.

PMID- 8754433
TI  - What is a "good" parent?

PMID- 8754434
TI  - Women's responses to Depo-Provera.

PMID- 8754435
TI  - Varicella zoster virus: trends and treatment.

PMID- 8754436
TI  - Short, shorter, shortest: continuing to improve the hospital stay for mothers and
      newborns.

PMID- 8754437
TI  - How parents describe caring behaviors of nurses in pediatric intensive care.

PMID- 8754438
TI  - Traditional values: are they in fact devalued?

PMID- 8754439
TI  - Elements of informed consent.

PMID- 8754440
TI  - Hydroxyurea in sickle cell disease.

PMID- 8754441
TI  - [Should lipid-lowering drugs be administered to normolipemic or mild hyperlipemic
      patients with coronary risk factors? Arguments for].

PMID- 8754442
TI  - [Should lipid-lowering drugs be administered to normolipemic or mild hyperlipemic
      patients with coronary risk factors? Arguments against].

PMID- 8754443
TI  - [Auricular fibrillation and stroke in patients with sick sinus syndromeusing
      permanent pacemakers].
AB  - INTRODUCTION AND OBJECTIVES: Since physiological pacing systems have become
      available, a debate has raged about the merits of atrial versus ventricular
      pacing in the sick sinus syndrome. The goal of this retrospective report was to
      study the long term incidence and the independent predictors for atrial
      fibrillation and stroke in 153 paced patients with sick sinus syndrome, adjusting
      for differences in baseline clinical variables with multivariate analysis. METHOD
      AND RESULTS: From 1980 to 1994, we implanted 32 dualchamber, 33 atrial, and 88
      ventricular pacemakers to treat patients with sick sinus syndrome. After a
      maximum follow-up of 177 months (median 30 months for paroxismal atrial
      fibrillation, 45 months for chronic atrial fibrillation and 43,5 months for
      stroke) the actuarial incidence of paroximal atrial fibrillation was 7.8% at 1
      year, 29% at 5 years and 42% at 10 years. The actuarial incidence of chronic
      atrial fibrillation was 1.3% at 1 year, 9.8% at 5 years and 22% at 10 years.
      Independent predictors for paroxismal AF from Cox's model was history of atrial
      tachyarrhythmias (p < 0.0001), chronic obstructive pulmonary disease (p = 0,006)
      and age (> 70 years-old) (p = 0.035). Only a history of atrial tachyarrhythmias
      before pacemaker implant was an independent predictor for chronic atrial
      fibrillation (p < 0.0001). The odd ratio for paroxismal atrial fibrillation in
      patients with previous atrial tachyarrhythmias and chronic atrial fibrillation
      were 6 (2.8-12) and 4 (1.6-9.7) (95% confiance limits). Actuarial incidence of
      stroke was 3% at 1 year, 10% at 5 years and 14% at 10 years. Independent
      predictors for stroke were history of peripheral vascular disease (p = 0.033) and
      hypertensive cardiomyopathy (p = 0.015). Development of paroxysmal and chronic
      atrial fibrillation during the follow-up were higher in patients with stroke (p <
      0.001 and p < 0.05). CONCLUSIONS: Development of atrial fibrillation and stroke
      in paced patients with sick sinus syndrome are strongly determined by clinical
      variables. Preimplant paroxysmal atrial tachyarrhythmias is the most important
      predictor for atrial fibrillation in the follow-up.

PMID- 8754444
TI  - [Clinical characteristics and hospital mortality of acute myocardial infarction
      in elderly patients treated with thrombolytic agents].
AB  - OBJECTIVES: This study describes the clinical features of elderly patients with
      acute myocardial infarction treated with thrombolytics and the effect of such
      therapy on in-hospital mortality rates in these patients. METHODS AND RESULTS: A
      group of 463 consecutive patients older than 70 years with an acute myocardial
      infarction was studied. This population was divided into two groups: 157 patients
      who received thrombolytic therapy (group A) and 306 patients who did not (group
      B). Patients in group A were younger (77 vs 79 years; p = 0.01) and had a lower
      prevalence of females (32.5% vs 44.1%; p = 0.01), prior myocardial infarction
      (14% vs 28%; p = 0.0008), hypertension (38% vs 48%; p = 0.03), diabetes (17% vs
      26%; p = 0.02), class Killip 3 at entry (3.5% vs 14%; p = 0.001), a higher
      frequency of Q wave MI (88% vs 50%; p = 0.0001), inferior location of MI (51% vs
      32%; p = 0.00007) and Killip 1 (70% vs 57%; p = 0.01) compared to group B. No
      significant differences on the inhospital mortality between either group were
      observed (25.5% vs 24.8%; p = 0.88). However, the thrombolysis was associated
      with higher mortality in patients with left ventricular dysfunction at entry (41%
      vs 84%; p = 0.0008) and in those patients with a delay of more than four hours
      from the onset of symptoms to admission (19% versus 30%; p < 0.1). CONCLUSIONS:
      1) In the elderly with acute myocardial infarction, thrombolytic therapy is
      administered to a lower risk population; 2) our findings do not confirm the
      benefits of chemical thrombolysis on cardiac mortality in the elderly, and 3) in
      selected subgroups (Killip > 2 at entry, symptoms delay > 4 hours) the
      risk/benefit ratio of thrombolytic therapy should be reevaluated. However, care
      needs to be taken in evaluating the data because this study was not blinded and
      the number of patients included was relatively small.

PMID- 8754445
TI  - [Wiktor stent in de novo lesions: immediate results in 100 consecutive patients].
AB  - BACKGROUND: Randomized trials which compare different stents are lacking and the
      studies to test the behavior of the Wiktor stent in de novo lesions have not been
      substantiated by large numbers and with consistent results. METHODS: The lesions
      were predilated with a conventional balloon 1/2 mm smaller in diameter than the
      stent to be used. The overdilation was done with the same balloon in which the
      stent comes mounted. The quantitative coronary analysis was "off line" by the
      automatic edge detection method with the CMS system by Medis. The post
      implantation treatment was aspirin and ticlopidine in most of the patients and
      they were discharged 24-48 hours after the procedure. RESULTS: In one hundred
      consecutive patients 112 Wiktor stents were attempted to treat 106 de novo
      lesions. All stents but one were successfully implanted. The quantitative
      coronary analysis of the treated lesions showed a pre-procedure minimal luminal
      diameter of 0.85 +/- 0.65 mm for a reference diameter of 3.18 +/- 0.49 mm. The
      minimal luminal diameter after stent implantation was 2.97 +/- 0.39 mm for a
      reference diameter of 3.42 +/- 0.46 mm. The diameter stenosis changed from 73 +/-
      18% pre-procedure to 13 +/- 9% after stent implantation. One patient was sent to
      emergency surgery. Another patient was referred for a semiselective bypass
      surgery. There was no mortality. One patient suffered a non Q wave myocardial
      infarction. There were no important bleeding complications. There were no cases
      of subacute thrombosis. All the patients were contacted by telephone one month
      after the procedure. CONCLUSIONS: In this study we have demonstrated that Wiktor
      stent implantation is associated with excellent immediate results. The new model
      makes stent implantation a rapid, safe and relatively easy procedure. If the
      angiographic result is good, there is no need for an stringent anticoagulation
      regimen. We have to wait for long term clinical and angiographic results to
      determine the role of Wiktor stent in novo lesions.

PMID- 8754446
TI  - [Elastic].
AB  - Since the ventricular myocardium is made up of a band of myocardial fibres which
      are configured into a complicated three-dimensional helical way, some time spent
      handling and observing this teaching model can help any cardiologist involved in
      imaging methods to understand and interpret the structural basis of the motion
      patterns of the heart. We concede that we need the cooperation of all disciplines
      to elucidate functional understanding of the myocardial band structure described
      above.

PMID- 8754447
TI  - [Myocardiopathies (XI). Restrictive myocardiopathy: concept, classification, and
      clinical approach].
AB  - Currently, cardiomyopathies are defined as "heart muscle diseases of unknown
      etiology". Restrictive cardiomyopathy is the rarest type of this disease, and the
      only one with no uniformly accepted diagnostic criteria. Its importance lies
      primarily in properly distinguishing it from constrictive pericarditis because of
      the direct consequences of mistakenly treating a case of constrictive
      pericarditis as if it were inoperable. Restrictive cardiomyopathy must be
      considered within the broader spectrum of diastolic dysfunction. Diagnostic
      criteria used show a general consensus for the diagnosis of restrictive
      cardiomyopathy in patients with clinical signs of heart failure in the presence
      of a nondilated, nonhypertrophic left ventricle with preserved contractility but
      abnormal diastolic function. Characteristically, right and left ventricular
      filling pressures are elevated and a dip and plateau diastolic pressure pattern
      appears. Restrictive cardiomyopathy may be either idiopathic and thus be a true
      cardiomyopathy in the strict sense of the term or secondary to an infiltrative
      disease of the myocardium. In this article we review the clinical and hemodynamic
      features of this disease and the different imaging techniques used in patients to
      help differentiate restrictive cardiomyopathy from constrictive pericarditis.
      Finally we study some types of restrictive cardiomyopathies.

PMID- 8754448
TI  - [Peritoneal migration of defibrillator implanted behind the rectus abdominis].
AB  - Automatic Implantable Cardioverter Defibrillator (AICD) has become a therapeutic
      option to malignant ventricular tachyarrhythmias. Its bulky device responds for
      discomfort and the likelihood of generator extrusion or migration, when implanted
      under the subcutaneous tissue. Among alternative sites, pre-peritoneal location
      has several advantages but hides its own risks. We present a generator peritoneal
      migration from a pocket made behind the rectus abdominis.

PMID- 8754449
TI  - [Depressed conduction and increased automaticity in acute septal myocardial
      infarction].
AB  - A patient with an established LBBB suffered an acute septal myocardial infarction
      complicated with a 2:1 infranodal AV block. As the ventricular rate decreased,
      the preexisting LBBB disappeared, and, in its place, a RBBB bradycardia-dependent
      appeared. Later on, an escape rhythm emerged, and competition between the two
      rhythms evolved. These disturbances were short-lived, and took place in the first
      24 h. It is postulated that an increase in the rate of diastolic depolarization,
      ischemia related, may cause, in the same area, impairment of conduction and
      increased automaticity accounting for the findings previously mentioned. In an
      acute septal infarction conduction disturbances usually are progressive; ischemia
      rarely may induce hypopolarization rise giving to complex, but reversible,
      phenomena.

PMID- 8754450
TI  - [Heart angiosarcoma and heart transplantation. Report of a case].
AB  - We present the case of a 29-year-old women with a cardiac primary angiosarcoma
      diagnosis. The initial symptom was a cardiac tamponade. The tests for screening
      metastasis proved negative. She was preoperatively treated with chemotherapy,
      followed by a heart transplant. There were no incidents related to surgery nor to
      the transplant except for a rejection in the second week biopsy. Four weeks after
      the transplant, the patient had a sudden dyspnea, the radiological tests
      confirmed the existence of a massive pleural overflow and lung and pleural
      metastasis. All types of therapeutical approaches were rejected except for
      pleurodesis. The patient died 60 days after the heart transplant.

PMID- 8754451
TI  - [Thrombocytosis and coronary disease. Report of a case].
AB  - We report the case of a young male with an inferior myocardial infarction who was
      treated with fibrinolytic agents and displayed a good evolution. The only
      cardiovascular risk factor that this patient had was an idiopathic thrombocytosis
      with abnormal platelet hyperreactivity tests. The angiogram showed an eccentric
      lesion of 60% in the left main coronary artery. A week later, after treatment
      based on anticoagulants and antithrombotic agents the angiogram was normal, and
      the lesion had disappeared. The association between these conditions is discussed
      the therapeutic approach is also discussed. A review of the literature is
      conducted.

PMID- 8754452
TI  - [Quality of life of patients with pacemakers].

PMID- 8754453
TI  - Toxigenic Corynebacterium diphtheriae acquired in England.

PMID- 8754454
TI  - Kicking the habit.

PMID- 8754455
TI  - Bonding amalgams.

PMID- 8754456
TI  - Serious deficiencies?

PMID- 8754457
TI  - Do conclusions make sense?

PMID- 8754458
TI  - Understated efficacy?

PMID- 8754459
TI  - Dental benefit found during orthopedic study.

PMID- 8754460
TI  - Sjogren's antibodies identified in saliva.

PMID- 8754461
TI  - Better assessments in half an hour.

PMID- 8754462
TI  - Do we need more research on the safety of amalgam and other materials.

PMID- 8754463
TI  - Root caries and root defects in urban and rural adults: the Florida Dental Care
      Study.
AB  - As part of the Florida Dental Care Study--a longitudinal study of risk factors
      for changes in dental health--the authors examined and interviewed 873 adults
      aged 45 years and older. During the examination, clinicians noted the number of
      teeth present and the participant's dental condition, including presence of root
      caries and fillings or noncarious defects on the roots. The interview was
      conducted to collect demographic and other information such as the adults'
      perceptions about dental care and their perceptions about their own dental
      health. The authors found that men, African-Americans, adults living in rural
      areas and those living in poverty were significantly more likely to have root
      caries than other participants. The data reported in this article will serve as
      baseline information for subsequent research.

PMID- 8754464
TI  - Assessing fluoride concentrations of juices and juice-flavored drinks.
AB  - Few studies have investigated fluoride exposures from juices and juice-flavored
      drinks manufactured with water. In this study, the authors analyzed 532 juices
      and juice drinks for fluoride. Fluoride ion concentrations ranged from 0.02 to
      2.80 parts per million, in part because of variations in fluoride concentrations
      of water used in production. Children's ingestion of fluoride from juices and
      juice-flavored drinks can be substantial and a factor in the development of
      fluorosis.

PMID- 8754465
TI  - Bringing impacted mandibular second premolars into occlusion.
AB  - Impaction of the mandibular second premolars is relatively rare and may offer
      general dentists and orthodontists special challenges during treatment. The
      authors discuss two cases involving impacted mandibular second premolars that had
      migrated before eruption. Surgical and orthodontic therapies were used to bring
      the teeth into occlusion. The authors emphasize early diagnosis and a
      collaborative approach between the dental professionals involved in treating
      these affected patients.

PMID- 8754466
TI  - Four common mandibular nerve anomalies that lead to local anesthesia failures.
AB  - Local anesthesia is essential in treating many dental and oral disorders.
      However, many types of anatomical anomalies are seen in the nervous system of the
      mandible that interfere with achieving local anesthesia. The authors describe
      four such anomalies and offer ways to overcome them when trying to properly
      anesthetize affected patients.

PMID- 8754467
TI  - Necrotizing sialometaplasia: literature review and case reports.
AB  - The authors describe necrotizing sialometaplasia, a benign inflammatory lesion
      primarily involving the minor salivary glands of the hard palate. The lesion
      presents itself as a deep-seated palatal ulcer with clinical and histologic
      features mimicking those of a malignant neoplasm. The lesion is believed to be
      the result of vascular ischemia initiated by trauma. An incisional biopsy is
      required to confirm the diagnosis, and the lesion heals by secondary intention
      within four to 10 weeks.

PMID- 8754468
TI  - A lifetime of motion: temporomandibular joints.

PMID- 8754469
TI  - Continuous quality improvement and dental practice: a marriage of necessity.
AB  - No business, regardless of its size, is ever problem-free. Continuous quality
      improvement is one way to keep businesses, including dental practices,
      functioning as near perfection as possible. The author discusses the value of CQI
      in the dental practice and outlines the principles of a CQI program.

PMID- 8754470
TI  - The financing and delivery of dental care: a nationwide survey of dentists.
AB  - The author surveyed a nationwide, stratified random sample of 560 dentists to
      ascertain their attitudes toward financing and delivery issues in dentistry.
      Women, younger and older dentists and nonmembers of the ADA tended to favor
      changing the current system of dental care delivery and financing. Respondents
      involved in public health and academia were most in favor of changes, followed by
      general practitioners, while specialists were least in favor of any change.
      Respondents with a higher percentage of patients receiving public medical
      benefits were significantly more in favor of changing the current system. The
      survey indicates that dentists' attitudes on these issues differ significantly.

PMID- 8754471
TI  - The bonding evolution in dentistry continues.

PMID- 8754472
TI  - Role of the subplate neurons in specification of neocortical areas.
AB  - Basing on literature the role of subplate neurons in specification of cortical
      areas is described. These neurons are required for thalamocortical pathfinding
      and they form a crucial link in cortical target recognition.

PMID- 8754473
TI  - The neuronal structure of globus pallidus in bison bonasus: Nissl and Golgi
      study.
AB  - The two subnuclei of globus pallidus have been investigated in the telencephalon
      of bison bonasus. The Nissl and Golgi procedures have been used to reveal their
      cellular organization. The Golgi preparation suggests the existence of two fairly
      divergent cellular subpopulations. The first class comprising the bulk of
      pallidal neurons consists of large efferent cells with long thick infrequently
      branching dendrites. The morphology of their dendritic processes is very complex
      and variable even in the one neuron (complex terminal endings, thin dendritic
      appendages, spiny segments, aspiny segments). Some of these structures (i.e.
      terminal endings, thin appendages) seem to be of presynaptic nature and allow one
      efferent neuron to influence on the functions of other large pallidal cells
      (interneuronal functions). The second one is composed of small interneurons with
      short highly arborized axons and thin varicose dendritic processes. Their
      distribution is very sparse and irregular in both segments of investigated
      nucleus.

PMID- 8754474
TI  - Microvasculature of the human fetal extra-ocular muscles. A SEM corrosion casts.
AB  - In the light of already known differences on the vascular patterns between slow
      and fast contracing skeletal and extra-ocular muscles (EOM) which has been
      described in both mammals and man we were interested to see if same of these
      features are presented in the human EOM during the second half of the gestation.
      Therefore the microvasculature bed of EOM was studied by SEM of vascular
      corrosion casting technique. 15 human embryos at 16-20 week of gestation, after
      spontaneous abortion, were used for this study. The vasculature bed of the all
      EOM studied is composed of two layers i.e. the orbital and the global. The
      orbital layer, in all specimens examined, has shown a relatively higher number of
      transverse anastomoses than the global one, although the capillary vessels were
      arranged similarly on the both sides.

PMID- 8754476
TI  - Extrarenal anastomoses of intrarenal fetal arteries with the arteries of
      surrounding structures.
AB  - In the corrosion casts of blood vessels from 21 human fetuses, the anastomoses of
      intrarenal arteries with the arteries of pararenal structures were studied. The
      anastomoses of intrarenal arteries with lumbar, testicular or ovarian,
      suprarenal, intestinal, retroperitoneal, and vertebral column arteries have been
      observed.

PMID- 8754475
TI  - Mastoid emissary in man. An anatomical-clinical study.
AB  - The purpose of the study was establishing differences in the situation of the
      external orifice of the emissary, its size and angle at which it leaves the
      skull. It is necessary for optimizaing of position for the internal coil of the
      speech processor of cochlear implant. As yet, the variability of external foramen
      of this emissary have not been sufficiently studied, especially in the clinical
      aspect with respect to the use of cochlear implants. The authors examined 200
      skulls of adults of both sexes. The statistically significant differences were
      observed between sexes and between sides of the body, and they showed a definite
      regularity. The variability of the site of the emissary is presented in a form
      useful for clinical purposes.

PMID- 8754477
TI  - Calices renales majores extrarenales.
AB  - In the material of 300 kidneys obtained from corpses of adults, extra-renal
      location of calices renales majores was observed in 3 of the organs. This
      developmental anomaly was accompanied with the variations of courses and division
      patterns of blood vessels within or in the vicinity of the renal hilus, whose
      characteristic feature was that they could cause the impairment of urinary
      outflow or urine retention.

PMID- 8754478
TI  - Arterial vascularization of the terminal ileum in human fetuses.
AB  - In 67 human fetuses of the crown-rump length from 58 mm to 285 mm (10 to 28 weeks
      of fetal age) the variability of the arterial vascularization of the terminal
      ileum was studied using the injection method. Three main angiomorphological types
      were distinguished on the basis of the frequency of occurrence of the ileocolic
      artery and the superior mesenteric artery ramifications and their contribution to
      vascularization of this part of the alimentary canal. Most frequent was found
      type I [46.3%] in which arterial supply of the terminal ileum stemmed from the
      recurrent ileal artery only or from the recurrent ileal artery and the superior
      recurrent artery. The type II [43.3%] was observed less frequently. In this type
      the terminal ileum was supplied by the recurrent ileal artery and the ileal
      branch of the ileocolic artery. In the most seldom type III [10.4%] the terminal
      ileum was vascularized by the stem of the superior mesenteric artery. The results
      were compared with those reported by other authors who studied the similar
      problem in adults.

PMID- 8754479
TI  - Structure of the multiorgan renal lymph node after blockade of its afferent
      lymphatics from kidney in the Wistar rats.
AB  - In 60 female rats histological structure of the left multiorgan renal lymph node
      was investigated after 4, 7, 14, and 28 days after selective blockade of the
      afferent renal lymphatics or nephrectomy. In experimental animals the renal lymph
      node showed changes in color and contained less macrophages with hemosiderine in
      comparison to control animals.

PMID- 8754480
TI  - [DNA prints instead of plantar prints in neonatal identification].
AB  - BACKGROUND: To check the possible usefulness in studying DNA in dried blood spots
      taken on filter paper blotters for newborn identification. It set out to
      establish: 1. The validity of the method for analysis; 2. The validity of all
      stored samples (such as those kept in clinical records); 3. Guarantee of non
      intrusion in the genetic code; 4. Acceptable price and execution time. MATERIAL
      AND METHODS: Forty (40) anonymous 13-year-old samples of 20 subjects (2 per
      subject) were studied. DNA was extracted using Chelex resin and the STR ("small
      tandem repeat") of microsatellite DNA was studies using the "polimerase chain
      reaction method" (PCR). Three non coding DNA loci (CSF1PO, TPOX and THO1) were
      analyzed by Multiplex amplification. RESULTS: It was possible to type 39 samples,
      making it possible to match the 20 cases (one by exclusion). The complete
      procedure yielded the results within 24 hours in all cases. The estimated final
      cost was found to be a fifth of that conventional maternity/paternity tests.
      CONCLUSIONS: The study carried out made matching possible in all 20 cases
      (directly in 19 cases). It was not necessary to study DNA coding areas. The
      validity of the method for analyzing samples stored for 13 years without any
      special care was also demonstrated. The technic was fast, producing the results
      within 24 hours, and at reasonable cost.

PMID- 8754481
TI  - [Validity of the protocol for evaluating the inappropriate use of
      hospitalization].
AB  - BACKGROUND: The study was carried out in order to assess the inter-observer
      reliability and validity in respect of clinical appraisal given by the
      Appropriateness Evaluation Protocol (AEP), in the context of the Spanish Public
      Hospital System. MATERIAL AND METHOD: In order to assess the reliability a total
      of 614 hospital stays chosen at random from 56 hospital admissions were
      independently analysed by three reviewers (two doctors and one nurse). In order
      to assess the validity, the findings obtained by the nurse were compared with the
      majority opinion given by the 7 hospital specialists in respect of each of
      hospital stays under evaluation. As part of the analytical procedure, indices for
      observed agreement, and specific agreement were calculated, as well as the Kappa
      statistic, all forming of various random samples of 614 hospital stays. In order
      to assess the predictive validity of the AEP, its sensitivity, specificity and
      predictive values were all measured against the majority clinical judgement.
      RESULTS: The study exhibited a high degree of inter-observer reliability
      (specific agreement > 64%, kappa > 0.75) and a reasonable validity in comparison
      with the consensus of opinions formed by a least 4 or 5 of its 7 clinical
      reviewers (specific agreement > 61%, kappa > 0.64), these values decreasing
      notably when the consensus of 6 or 7 of the reviewers was required. The AEP
      revealed a high degree of sensitivity and a low degree of specificity in
      comparison with the majority clinical assessment, thus minimising the occurrence
      of false results when the stay was regarded as appropriate, and producing false
      negatives (appropriate hospital stays regarded as inappropriate) varying in
      degree from moderate to very high. CONCLUSIONS: The results showing high
      reliability and moderate validity regarding clinical assessment shows the AEP to
      be a useful instrument in the sifting-out of inappropriate use of
      hospitalisation, although they do not allow a definitive judgement to be made
      concerning the efficiency of hospital services nor judgements regarding
      individual cases.

PMID- 8754482
TI  - [Primary meningococcal conjunctivitis: implications beyond the conjunctiva].
AB  - BACKGROUND: Neisseria meningitidis is a uncommon cause of acute bacterial
      conjunctivitis. However, its diagnosis has important therapeutic implications.
      METHODS: From December 1993 to January 1984, a prospective study on acute
      bacterial conjunctivitis was performed at the Hospital Universitario Materno
      Infantil Vall d'Hebron. Primary meningococcal conjunctivitis (PMC) was diagnosed
      in 34 patients. The diagnosis of PMC was made on the basis of consistent clinical
      manifestations together with isolation of Neisseria meningitidis from
      conjunctival exudate culture. RESULTS: There were 16 men and 18 women with a mean
      age of 3.5 +/- 3.3 years. PMC was bilateral in 7 patients and unilateral in 27.
      Initial therapy for PMC included only topical antibiotics in 24 patients and
      systemic antibiotic therapy in 10. Ten patients (29.4%) developed invasive
      meningococcal disease. None of the patients died neither developed ocular
      sequelae. Forty one percent of the patients who received only topical therapy and
      none [corrected] of those who received systemic therapy, developed invasive
      meningococcal disease (p = 0.04). CONCLUSIONS: PMC may represent the portal of
      entry for invasive meningococcal disease, which occurs in almost a third of
      patients. Patients with PMC and higher risk of developing invasive meningococcal
      disease are those treated only with topical antibiotic therapy.

PMID- 8754483
TI  - [In search of the lost imprint].

PMID- 8754484
TI  - [Planning and assessment of ambulatory care in for drug addiction].

PMID- 8754485
TI  - [Occult involvement of bone marrow in Hodgkin's disease: detection with magnetic
      resonance].
AB  - Although bone marrow biopsy is considered the best procedure to detect bone
      marrow involvement by Hodgkin's disease (HD), in recent years several studies
      have emphasized the value of magnetic resonance imaging (MRI). We present the
      case of a patient with HD apparently localized in a laterocervical lymph node,
      who also referred disestasiae at a region corresponding to D10 metamera. Bone
      marrow biopsy, vertebral TC and 67-Ga scintigraphy were all normal. However, a
      node of 1 cm in diameter was detected by MRI in the tenth dorsal vertebra.
      Because of the topographic coincidence between the patient's symptomatology and
      the MRI findings, the HD was considered to be in advanced stage and CMOPP/ABV
      chemotherapy was administered, this resulting in a rapid improvement of symptoms
      and disappearance of the MRI abnormalities. Since in the present case, the MRI
      determined a change in disease stage and treatment, the role of MRI as a
      complementary exploration of bone marrow biopsy to detect marrow involvement by
      HD is reviewed.

PMID- 8754486
TI  - [New vaccines and the immune response (I). Immunologic memory. Humoral response
      versus cellular response].

PMID- 8754487
TI  - [Domiciliary internists].

PMID- 8754488
TI  - [Prevalence of Cryptosporidium and Giardia in different population groups].

PMID- 8754490
TI  - [Is it always necessary to use the double-blind method in controlled clinical
      trials?].

PMID- 8754489
TI  - [Mediastinal mass and multiple lung cavitations as presentation form of Hodgkin's
      disease].

PMID- 8754491
TI  - [The need to develop new prescription models].

PMID- 8754492
TI  - [Prehospital delay in patients with ischemic chest pain in the Province of
      Alicante. Multicenter Study of Prehospital Delay in Patients with chest Pain].
AB  - BACKGROUND: The objectives of this study are: 1) to estimate the pre-hospital
      delay between onset of symptoms and admission in patients with ischemic chest
      pain in 5 hospitals from the Spanish Region of Valencia, and 2) to determine the
      socio-demographic variables that are associated with this delay. PATIENTS AND
      METHODS: We studied prospectively 426 patients admitted to the emergency area of
      the 5 participating hospitals with chest pain and a probability of infarction >
      or = 0.08. In each patient we determined the probability of acute myocardial
      infarction, the length of time between onset of symptoms and hospital arrival
      (patient's decision time and transportation time), and some socio-demographic
      variables presumably related to the delay. RESULTS: The median between onset of
      symptoms and arrival to the hospital was 120 minutes, corresponding the biggest
      part to decision time (median 73 minutes), whilst the median of transportation
      time was 20 minutes. Cox's regression analysis identified the following
      independent predictors of delay: age of the patient (p = 0.012), living with
      relatives (p = 0.026), onset during the night (p < 0.001) or at home (p = 0.021),
      low severity of pain (p < 0.001), being autoctonous (p = 0.023) and participation
      of health care individuals in the referral process (p = 0.011). CONCLUSIONS: The
      pre-hospital delay detected in our study is comparable to that detected in other
      settings. The determinants of the delay identified in this study are consistent
      with previously published findings.

PMID- 8754493
TI  - [Treatment with fludarabine of lymphoid neoplasms with low grade malignity
      resistant to treatment or in relapse].
AB  - BACKGROUND: In the last years the treatment of patients with chronic lymphocytic
      leukemia (CLL) and low-grade lymphomas (NHL) has changed because of the
      introduction of new agents, mainly the purine analogs. We report our experience
      with fludarabine in patients with indolent lymphoid malignancies that were
      previously treated with conventional agents. PATIENTS AND METHODS: Twenty
      patients were studied. Eleven had CLL and nine NHL. Among the patients with CLL
      and NHL, 72 and 100%, respectively, had advanced disease. All patients had
      previously been treated. Fludarabine was administered by intravenous infusion at
      a dose of 25 mg/m2, for 5 days every 4 weeks until a maximum of 6 cycles.
      RESULTS: Neither complete response (CR) nor partial response (PR) was recorded in
      patients with CLL; 4 (36%) achieved clinical improvement. Among the 9 patients
      with NHL, 3 (33%) had a CR and one a PR; two of the 3 patients with CR also
      achieved a molecular remission. In 3 patients with CLL their disease progressed
      from stage II to IV. Three patients (one with CLL and two with NHL) developed
      high-grade lymphoma during or immediately after the treatment with fludarabine.
      The major toxicities were infections: 3 patients had lobar pneumonia and one an
      interstitial pneumonia without microbiological identification. CONCLUSIONS:
      Fludarabine is an active agent in patients with low-grade lymphoid malignancies
      refractory to the treatment or in relapse. The possibility of obtaining molecular
      remissions makes this agent specially interesting in those therapies including
      hemopoietic progenitors transplantation as intensification treatment.

PMID- 8754494
TI  - [Expression of pS2 protein in breast cancer and its relationship with estrogen
      and progesterone receptors].
AB  - BACKGROUND: We studied pS2 protein in breast tumors and its relation with
      estrogen and progesterone receptors and with anatomopathological characteristics
      of the tumors. MATERIAL AND METHODS: We measured the pS2 content (by IRMA) and
      steroid receptors content (by EIA) in 151 breast tumors. Results were compared
      and correlated with tumoral characteristics. RESULTS: 53% of tumors were pS2+.
      Among them, 91% were estrogen receptors +.86% of estrogen receptors negative
      tumors were pS2-. We observed correlation between pS2 and estrogen receptors
      values (r = 0.56; p < 0.0001) and between pS2 and progesterone receptors values
      (r = 0.53; p < 0.0001). Distributing the tumors in pS2+ and pS2-, we observed
      association between pS2+ and estrogen receptors + (chi 2 = 45.6; p < 0.0001) and
      pS2+ and progesterone receptors + (chi 2 = 43.1; p < 0.0001). However, we found a
      18.5% of estrogen receptors + pS2- tumors. We observed a significant difference
      between GII and GIII tumoral grades (chi 2 = 5.51; p < 0.019), with a majority of
      pS2+ tumors in GII and pS2- tumors in GIII. CONCLUSIONS: The estrogen receptors
      in estrogen receptors + ps2- tumors may be non functional. The presence of pS2
      protein alternative to that of progesterone receptors may indicate a functional
      heterogeneity of the estrogen receptors system, which is of interest in
      evaluating prognosis and response to the hormonal therapy.

PMID- 8754496
TI  - [In search of Eldorado. Breast cancer and intensification therapy].

PMID- 8754495
TI  - [Delay in the diagnosis and treatment of patients with ischemic chest pain: how
      and why we should improve].

PMID- 8754497
TI  - [Transient cerebral and bone marrow ischemia in patients with atrioseptal
      aneurysm].
AB  - The relationship between atrioseptal aneurysm and ischemic stroke has not been
      clearly demonstrated. We present three patients with transient cerebrovascular
      events and one patient with transient medullar ischemia related with the presence
      of atrioseptal aneurysm. Other causes of cerebrovascular disease have been
      excluded. Following anticoagulation treatment all the patients remain
      asymptomatic.

PMID- 8754498
TI  - [Insulin resistance, calcium cell metabolism, and essential arterial
      hypertension. Role of skeletal muscle].

PMID- 8754499
TI  - [A 69-year-old woman with predominantly proximal muscle weakness for 6 years].

PMID- 8754500
TI  - [Sarcoidosis and HIV infection].

PMID- 8754501
TI  - [Somatization disorder in primary health care].

PMID- 8754502
TI  - [Angiocentric pulmonary T-cell lymphoma associated with primary Sjogren
      syndrome].

PMID- 8754504
TI  - Onchocerciasis.

PMID- 8754503
TI  - [Effect of granulocyte colony-stimulating factor after chemotherapy with CHOP in
      patients with non-Hodgkin's lymphoma and HIV infection].

PMID- 8754505
TI  - [Improvement in the system for introducing scientific research results into
      expert practice].

PMID- 8754506
TI  - [Establishing the time of death by the putrefactive transformation of the
      corpse].
AB  - Electron paramagnetic resonance (EPR) was used for assessing the time of death.
      The kinetics of the reaction of the rate of recovery of spin probes incubated
      with homogenized muscle tissue was studied by repeatedly recording the central
      component of the probe followed by measuring its amplitude. Muscle tissue of 35
      corpses was studied 7 to 182 days postmortem with a one-week interval. The
      results indicate that EPR may help assess the time of death in corpses
      transformed by putrefaction. The amplitude of the central component of spin probe
      EPR spectrum is recommended as the criterion of assessing the length of
      postmortem period.

PMID- 8754507
TI  - [The characteristics of bone injuries in childhood].

PMID- 8754508
TI  - [The characteristics of the gunshot injuries inflicted by a gas-barrel weapon].

PMID- 8754509
TI  - [The forensic medical characteristics of the shot injuries caused by a gas-barrel
      weapon].

PMID- 8754510
TI  - [The planning of forensic medical osteological studies in the expertise of
      personal identification].

PMID- 8754511
TI  - [The establishment of osteogenesis imperfecta for personal identification].
AB  - Anatomical, clinical (including X-ray), microscopic, and ultrastructural features
      of osseous tissue were studied in 32 subjects suffering from congenital
      osteopsathyrosis, osteogenesis imperfecta, aged 0 to 38 years. The findings
      showed that bone tissue was sharply rarefied, with the amount of the base
      substance reduced and the number of osteocytes per unit of its area increased.
      This sign, typical of the disease in question, is still observed in putrefied
      corpses. Electron microscopy revealed decrease of granular endoplasmatic
      reticulum in osteoblasts with impaired maturation of collagen fibrils and their
      mineralization.

PMID- 8754512
TI  - [The craniometric individuality of the human skull].
AB  - Experimental findings indicate that if the basic position of the skull is
      assessed visually (as is usually done in expert photocombination), various video
      images of the same skull never fully conform to each other, the deviations
      reaching 1.5 and more degrees. As a result of this, the accuracy of determining
      the reference points on the video image varies from 1.-1.5 to 4.0-4.5 mm (en
      face) and 1.5-2.0 to 6.0-6.5 mm (profile). The task of identification of two
      images of the skull is reliably solved in 87.7% cases, and in 12.3% cases the
      results may be false-positive or false-negative. The individuality of the skull,
      that is, the impossibility of its replacement during computer-aided
      photocombination is realized in the absence of aspect distortions and minimal
      errors of measurements. Hence, a new technology of studies is to be introduced:
      coordination-monitored stable complex of video camera and computer with metric
      monitoring of all parameters liable to change.

PMID- 8754513
TI  - [Criteria for determining the degree of severity of body injuries with the
      presence of foreign bodies in the gastrointestinal tract].
AB  - The authors analyze 303 cases with foreign bodies in the gastrointestinal tract,
      discuss the rightfulness of referring such foreign bodies to corporal injuries,
      and validate the necessity of assessing the severity of such injuries. Opinions
      of forensic medical experts vary in such cases. A methodological approach and
      criteria for assessing the severity of corporal injuries inflicted by foreign
      bodies in the gastrointestinal tract are proposed.

PMID- 8754514
TI  - [The frequency of ABO blood groups and the expression of group antigens and
      isohemagglutinins in Syrian Arabs].
AB  - Syrian Arabs more often have blood groups A and 0 (46.25 and 37.50%,
      respectively) and less frequently group B (13.13%) than Slavs; group AB occurs in
      Arabs almost twice more rarely than in Slavs and is a rare blood group for them
      (3.12%). On the whole, the expression of group antigens A and B and
      isohemagglutinins alpha and beta is normal in Arabs. Antigen H of group 0(I) is
      an exclusion: it is expressed in Arabs much more intensively than in a control
      group of Slavs (residents of Kiev). The cause of very high titers of group
      antibodies in an appreciable part of residents of Kiev is unclear.

PMID- 8754515
TI  - [Exogenous organic psychoses and their differential diagnosis in the forensic
      psychiatric clinic].
AB  - Forty-two male patients with organic involvement of the brain of various origins
      with different severity of psycho-organic changes were examined in order to
      detect the structural and dynamic clinical features of exogenous organic
      psychoses for forensic psychiatric expert evaluation. Four variants of such
      psychoses were distinguished (acute, protracted, relapsing, and periodical),
      depending on the conditions of development and syndrome formation. Their clinical
      manifestations are described, forensic psychiatric approaches defined, and
      variants of forensic psychiatric evaluation presented.

PMID- 8754516
TI  - [The civil legal procedural competence of schizophrenia patients].
AB  - Discusses the methodological problems of forensic psychiatric evaluations of
      mental disorders in the structure of the most incident endogenous psychosis,
      schizophrenia, under conditions of expert evaluation in a civil process. Presents
      criteria permitting the differentiation between pathological states.

PMID- 8754517
TI  - [Law infringements by adolescents with borderline psychoneurotic disorders].

PMID- 8754518
TI  - [The assessment of the degree of severity of facial trauma].

PMID- 8754519
TI  - [The organizational interaction of a bureau of forensic medical expertise with
      subjects having obligatory medical insurance at a territorial level].
AB  - Presents data on the organization of interactions between the Bureau of forensic
      medical expert evaluation and obligatory medical insurance bodies in cases with
      forensic medical examination of the corpses of inpatients. Demonstrates the role
      of forensic medical expert evaluation in improving the quality of guaranteed
      medical care to the population under conditions of insurance medicine and the
      possibility of extra financing in such cases.

PMID- 8754520
TI  - [A case of fatal carbon dioxide gas poisoning].
AB  - Presents a rare case with mortal poisoning with carbon dioxide in an industrial
      setting. A refrigerator worker lost consciousness in a chamber for dry ice and
      the corpse was removed after 25 min. The author emphasizes the significance of
      contacts of the expert with legal bodies, administration, and witnesses of the
      accident.

PMID- 8754521
TI  - [The morphological criteria and proposed mechanisms of cortical contractility in
      oocytes of the clawed toad].
AB  - It is proposed to consider certain states of the cortical actin cytoskeleton
      corresponding to various stages of oocyte maturation as morphological criteria of
      the cortical contractility during progesterone-induced oocyte maturation. In the
      definitive oocyte, the cortical microfilaments form an anisotropic network, while
      in the mature egg, they form an isotropic disorganized network and, at the moment
      of contraction, bundles. Factors of the actin cytoskeleton transformation are
      discussed: actin-binding proteins, protein kinases, and bivalent ions. The data
      are given on the presence and distribution of the actin-binding protein vinculin
      in the cortex of the oocyte.

PMID- 8754522
TI  - [A new class of small RNP (alpha-RNP) containing antisense RNA in K-562 cells. I.
      Their characteristics and changes during erythroid differentiation].
AB  - A new class of small RNP (alpha-RNP) has been detected and identified in nuclei
      and cytoplasm of A-562 erythroid leukemia cell line; these RNPs have a
      characteristic spectrum of proteins containing conservative and specific
      components and a special RNA component, which contains a small antisense
      component (alpha-RNA), a homolog of short dispersed Alu repeats. alpha-RNP is
      highly stable, tightly associated with chromatin in the nucleus, and is found in
      the free state in cytoplasm. The composition of nuclear and cytoplasmic alpha-RNP
      differ and have a specific pattern of changes in response to dimethylsulfoxide,
      an agent causing differentiation.

PMID- 8754523
TI  - [A new class of small RNP (alpha-RNP) containing antisense RNA in K-562 cells.
      II. The interaction of the RNA--the alpha-RNP component--with heterogeneous
      nuclear and messenger RNA in the normal state and under DMSO exposure].
AB  - Small antisense RNA (alpha-RNA), components of a new class of small nuclear and
      cytoplasmic RNP (alpha-RNP) identified in the cells of K-562 human
      proerythroleukemia cell line, are capable of hybridizing under stringent
      conditions with precursors of mRNA (heterogeneous nuclear RNA or mRNA) and with
      mRNA of these cells. We found that DMSO, an agent inducing differentiation in K
      562 cells, is capable of regulating the composition of alpha-RNA population and
      concomitantly changes the content of mRNA that has regions homologous
      (complementary) to alpha-RNA. Specifically, it has been demonstrated that DMSO
      decreases the level of alpha-RNA, which hybridizes with the actin gene. Results
      of restriction mapping of regions of complementary interaction of alpha-RNA with
      the actin gene point out that alpha-RNA hybridizes with regions containing the
      promotor area and 3'-nontranslated area of the gene. It is proposed that small
      antisense alpha-RNA (alpha-RNP) participates in the control of gene expression at
      posttranscriptional level in cell cytoplasm.

PMID- 8754524
TI  - [The tissue antioxidant system in the early postnatal development of rats].
AB  - We studied the total antioxidant activity, as well as the activity of the water
      soluble portion of the antioxidant system and the activity of catalase and
      superoxide dismutase in the brain, liver, heart muscle, skeletal muscle, kidneys
      and blood serum of 1, 4, 6, 30, and 90-120-day-old rats. High antioxidant
      activity was detected in the tissues of the newborn animals. In the majority of
      the tissues, the total antioxidant activity and catalase activity peaked at days
      14-30 of development. Some tissue specificity of age-related changes has been
      found for individual components of the antioxidant system.

PMID- 8754525
TI  - [Obtaining eggs and the transplantation of microinjected zygotes in rabbits].
AB  - A system of preparation of donors and recipients, providing for the optimal
      reaction of donors to superovulation, good survival of zygotes after
      transplantation, and high degree of fertility of the recipients, is characterized
      within the framework of gene and embryo transfer programs in rabbits. The
      technique of laparoscopy a fast and efficient method of nonsurgical
      transplantation of zygotes in rabbits, is described.

PMID- 8754526
TI  - [The biosynthesis of cortisol and its regulation by the adrenocorticotropic
      hormone in the adrenals of silver fox embryos].
AB  - We studied the cortisol level in blood serum and adrenal homogenates, as well as
      the in vitro production of cortisol in adrenals of silver fox embryos of both
      sexes in response to exogenous adrenocorticotropic hormone (ACTH) stimulation.
      The level of cortisol in blood serum did not show any significant changes during
      the embryo development, while its level in adrenals and production by adrenals in
      vitro increased progressively from Day 35 to Day 50 of prenatal life. We found
      that ACTH is capable of stimulating cortisol biosynthesis and production in vitro
      during all studied periods of embryogenesis.

PMID- 8754527
TI  - [Audiogenic epilepsy in 101/HY mice at different periods of postnatal
      development].
AB  - It has been established that mice of strain 101/HY suffer from audiogenic
      epilepsy seizures, the frequency and severity of which depend on animal sex and
      age. Mice were subjected to high intensity sound (about 100 dB) at the age of 14
      16, 30, 60, and 190-270 days (Groups I, II, III, and IV, respectively). The
      testing was done three times. Mice of Group I were tested twice. The duration of
      sound stimulus was 20 s. Mice of both sexes from Group I were most sensitive.
      During the first test, the so-called "wild-run" behavior developed in 90% of
      animals and 60% showed tonoclonic seizure. Lethal outcomes in animals of this
      group (26.7% of the males and 23.5% of the females) were observed mainly during
      the second test, conducted one day after the first one. Only 6.7% of the males
      died during the first test in Group I. Severity of audiogenic seizure in males
      decreased with age, whereas among females there was a decrease in the number of
      animals with sensitivity to the sound stimulus. Among females of Groups III and
      IV, we did not detect any animals responding to the audiogenic stimulus by
      seizure and there were no deaths. Mechanisms underlying the audiogenic
      sensitivity of 101/HY mice are reviewed in the light of other information about
      the development of this genetic trait in rodents and in connection with other
      biological characteristics of these animals.

PMID- 8754528
TI  - [The effect of the mutant genes Ta, Ra and Sd on early embryogenesis in mice].
AB  - We studied early embryonic mortality of mice from mutant stocks Tabby (Ta, X
      chromosome) and RaSd (RaSd/++, chromosome 2) maintained in the heterozygous state
      in F1 CBA x C57B1/6 hybrid. Tabby and RaSd mice were reciprocally crossed with F1
      mice and examined for the morphological status of embryos washed from the oviduct
      on the third day of pregnancy, when the stage of eight blastomeres is normally
      attained. Mortality was evaluated from the number of embryos which did not reach
      the expected stage by this time. The results have shown that 2-4 cell embryos,
      which have received gene Ta with the X-chromosome of the female parent, differed
      from embryos with F1 genotype at the same stage of development by their increased
      mortality rate, whereas among embryos obtained from RaSd, the mortality was
      mainly observed before cleavage. Death of embryos receiving the mutant gene from
      hemizygous Ta males or heterozygous RaSd/++ males was not significantly different
      from the mortality of embryos without these mutations.

PMID- 8754529
TI  - [The characteristics of the contact area of an endoprosthesis made from Ostek
      graphite-based material and of the mandibular bone fragment].
AB  - Interactions between endoprostheses made of carbonic composition "Ostec" and bone
      tissue were studied after plastic repair of experimental vast defects in the
      mandible in 22 rabbits and 10 dogs over the course of 2 years. Histologic
      findings showed the formation of a layer of fibrous connective tissue 3 months
      after the operation and later; at some places the implant directly joins the
      rabbit bone, which frequently undergoes chondroid transformation.
      Microscopically, the structure of "Ostec" represents carbonic threads forming
      large bundles. By the 6th and 12th months of experiment connective tissue
      elements penetrate the fissures between the bundles and the perforation gaps of
      the endoprosthesis, forming bone-like and bone structures in them.

PMID- 8754530
TI  - [The structural properties of the saliva in the modelling of a cariogenic
      situation].
AB  - A cariogenic situation was modeled by soft acidification by hydrochloric acid in
      vitro in mixed salivary pool of 10 subjects aged 16-18, and the values of pH and
      active concentration of sodium ions, optic density, and concentration of
      inorganic phosphorus were studied. Soft acidification of human mixed saliva was
      found to result in its structural disorders. The saliva of subjects with
      negligible caries was more stable to unfavorable exposure than mixed saliva of
      subjects with a higher CFL index. Experiments showed that pH of 6.2 is the
      critical value causing evident destruction of the saliva and reducing its
      mineralizing potential. These data may be used in studies of the molecular
      mechanisms of caries development.

PMID- 8754531
TI  - [Nitric oxide (NO) inactivation by polymorphonuclear leukocytes as a mechanism
      for the development of periodontal lesions].
AB  - To investigate the mechanism by which polymorphonuclear leukocytes (PMNLs)
      contribute to tissue injury in periodontitis, NO-activity was bioassayed by
      measuring its ability to increase cGMP accumulation in cultured fibroblasts in
      the absence or presence of PMNLs isolated from blood and gingival fluid in
      healthy volunteers and patients with periodontitis. Non-activated PMNLs do not NO
      induced stimulation of cGMP accumulation in the detector cells. However,
      activated PMNLs inhibited NO-induced cGMP accumulation whereas the effects of
      sodium nitroprusside was unaffected. Peripheral PMNLs periodontitis impaired NO
      dependent cGMP accumulation more markedly than from healthy volunteers. PMNLs
      from periodontal pockets in periodontal patients destroyed NO significantly
      higher than in venous blood of the same patients without additional activation.
      It is assumed that the deactivation of NO by activated PMNLs is a one of the
      pathomechanisms of disorders in periodontitis.

PMID- 8754532
TI  - [Changes in the oral mucosa in chronic secondary disease].
AB  - Four patients with acute leukemia suffering from a chronic secondary illness
      (CSI) which developed 1.5 to 34 months after allogenous transplantation of bone
      marrow are described. One patient (female) was followed up over time: 14, 15, and
      20 months after CSI was diagnosed, the rest patients were examined once, 15.5,
      23, and 29 months, respectively, after the disease was diagnosed. Besides visual
      characterization of the buccal mucosa, results of cytologic examination of smear
      impressions are presented. Specific features of mucosa involvement at the peak of
      clinical manifestation of CSI and later, when the rest symptoms of secondary
      disease to a certain measure regressed, are described. The authors emphasize a
      similarity between the detected changes in the buccal mucosa and those observed
      in diseases which might be caused by immunity disorders.

PMID- 8754533
TI  - [The role of risk factors in the development of a hemoendothelial imbalance in
      periodontal diseases].
AB  - The given piece investigates the spreading of parodontitis in Armenia in linkage
      with such factors as diabetes, arthritis, stresses which have proved to have
      their influence on leukocyte-endothelial balance. The spreading of various forms
      of parodontitis was revealed with almost 70% of the examined among Armenian
      population. For patients with diabetes, arthritis and its combination with
      arterial hypertension this indicator grew up to 90%. The number of patients with
      parodontitis has especially increased. A drastic increase of markers of
      endothelia disorganization was observed among these patients in comparison with
      all the other examined groups. The growth of the levels of the investigated
      markers remains dependent on the seriousness of the generalized paradontitis.

PMID- 8754534
TI  - [Microbiocenosis study in chronic diseases of the oral mucosa].
AB  - Examinations of 18 patients with recurrent aphthous stomatitis, 8 with ulcerative
      necrotic gingivitis, 10 with lichen planus, 10 with herpetic stomatitis, and of
      24 patients without evident clinical symptoms of buccal mucosa involvement but
      complaining of various stomatogenic sensations, e.g. burning, tightness, pain and
      pricking in the buccal mucosa, perverted taste, etc., showed that chronic
      diseases of the buccal mucosa involve expressed shifts in the microbiocenosis,
      namely, dysbacteriosis of different severity.

PMID- 8754535
TI  - [Comments on scientific reports on the problems of periodontology].
AB  - The most frequent mistakes in dental papers are analysed. The first part of
      mistakes is an incorrect use of modern classification of periodontal disease. The
      second--about of adequate periodontal and epidemiological and clinical
      investigations and very adequate controls--for providing the results most
      correct.

PMID- 8754537
TI  - [The pathogenesis of surgical trauma and the characteristics of its course in
      planned surgical interventions in the maxillofacial area].
AB  - Examinations carried out on 76 patients have shown that systematic surgical
      interventions into the maxillofacial area produce deep changes in the tissue and
      serum systems of proteolysis and their inhibitors. Activation of proteolytic
      enzymes already on the stage of surgical trauma leads to the formation in the
      operative wound of the focus of endotoxicosis which depresses antitryptic
      activity of injured tissues and thus promotes the development of purulent
      complications. The study of the above indexes at the early stages of acute period
      may serve as a diagnostic test while estimating a severity of operative wound and
      allows to make prognosis of the development of purulent complications.

PMID- 8754536
TI  - [Tactivin in the combined treatment of acute inflammatory diseases of the
      maxillofacial area].
AB  - Examinations of 46 patients with acute inflammatory diseases of the maxillofacial
      area revealed a reduction of some immunity parameters. Thymic activity of the
      saliva and blood was found to reduce still more after surgery (opening of the
      phlegmon). The ratio of thymic activities of the saliva and blood may be an
      indirect evidence of a tendency in development of an inflammatory process. The
      authors demonstrated the efficacy of correcting immunity parameters by tactivin,
      which was particularly effective in grave cases. Tactivin concentrations in the
      blood and saliva, their time course and ratio may be considered as additional
      criteria for assessing the status of patients and the risk of complications.

PMID- 8754538
TI  - [The clinico-laboratory characteristics and diagnosis of acute stomatogenic
      sepsis].
AB  - Thirty-four patients with acute stomatogenic sepsis developing in grave
      ulcerative necrotic stomatitis (including that in Stevens-Johnson's and Lyell's
      syndromes) were examined. Homeostasis parameters were shifted in these patients.
      To facilitate timely diagnosis of acute stomatogenic sepsis, the authors offer a
      differential diagnostic table. Patients with grave forms of stomatitis are
      recommended to be referred for examination and treatment to specialized dentistry
      hospitals in order to early diagnose the disease and prevent the development of
      acute sepsis.

PMID- 8754539
TI  - [The clinical x-ray variants of the osteolytic forms of rheumatoid arthritis of
      the temporomandibular joint].
AB  - Patients with grave forms of generalized rheumatoid arthritis characterized by
      high activity and fulminant course are liable to develop osteolytic variants of
      destructive processes. Clinical and x-ray variants of osteolysis are as follows:
      surface (50%), partial (38%), and complete (22%). X-ray examination showed
      pseudodilatation of the articular fissure and blurred and destroyed articular
      surfaces. Osteolysis eventuates in the development of a false joint or fibrous
      ankylosis.

PMID- 8754541
TI  - [The use of tactivin in the combined treatment and prevention of complications in
      reconstructive operations on the bones of the facial skeleton].
AB  - Sixty-three patients with congenital and acquired defects and deformations of
      facial bones without concomitant diseases were examined. Twenty-eight of them
      were operated on; auto- and alloplasty was resorted to in 18 patients, and to 10
      patients tactivin was administered after common protocols for immunocorrection
      before or after surgery. Immunologic and clinical studies showed that
      immunodeficiency states are the most probable causes of postoperative
      complications following repair surgery on the facial bones. Tactivin normalized
      the immunity parameters and prevented the development of postoperative
      complications.

PMID- 8754540
TI  - [The pathogenetic formation of facial skull deformities].

PMID- 8754542
TI  - [A modified method for the surgical treatment of patients with maxillary retro-
      and micrognathism].
AB  - A method of surgical treatment of patients with upper retro- and micrognathia is
      proposed, consisting in improving the fixation of osteotomied maxillary complex.
      Implantation of carbonic ceramics behind the maxillary tubercles and
      osteosynthesis of bone fragments with titanium miniplates helps do without
      prolonged intermaxillary fixation and permits exercise in the early postoperative
      period, thus cutting down the invalidity period. Analysis of the results attained
      in 14 patients showed no relapses of maxillary deformation and a stable
      functional and esthetic effect.

PMID- 8754543
TI  - [Endoprosthesis of the cranium and facial skull with perforated plates made of
      titanium].
AB  - Perforated titanium plates were effectively used as endoprostheses in 137
      patients with extensive posttraumatic defects of cerebral and facial skull bones.
      Use of these plates appreciably accelerated the operation. Due to exceptional
      qualities of truly pure medical titanium these plates are absolutely biologically
      inert.

PMID- 8754544
TI  - [The effect of the initial level of mineralization of the erupting molars on
      their caries susceptibility].
AB  - A method for predicting caries of permanent molars at the stage of enamel
      mineralization has been developed. It is based on measuring the electric
      conductivity of hard dental tissues. A total of 100 children have been examined
      over time (for 7 years), starting from the age of 5 to 6 when permanent molars
      are just erupting and after they appear. The erupting molars are characterized by
      different levels of mineralization which determines tooth resistance or liability
      to caries. The initial level of mineralization of erupting molars is the earliest
      and sufficiently objective prognostic criterion which helps start individual
      preventive measures.

PMID- 8754545
TI  - [The assessment of the stomatological status of children living in radionuclide
      contaminated areas].
AB  - Dental status of 1051 children aged 3 to 13 living at Byelorussian territories
      polluted by radionuclides (Gomel and Mogilev districts) was examined in 1993
      1994. Examinations revealed high incidence of caries, poor oral hygiene, high
      incidence of various pathological shifts in the buccal mucosa and red lips. The
      temperature and nonspecific resistance of the mucosa were reduced. Changes of the
      buccal mucosa were more expressed in younger children.

PMID- 8754546
TI  - [The relative role of hereditary and environmental factors in the formation of
      the maxillodental system].
AB  - The contribution of hereditary and environmental factors to the formation of
      maxillodental abnormalities in the ontogenetic aspect was analyzed using a twin
      model. A total of 80 twin pairs aged 3 to 18 were examined. The results permitted
      the authors define the age periods favorable for therapeutic and prophylactic
      measures in children with abnormalities of the teeth, dentition, and occlusion.
      Effects of sex dimorphism on the parameters of the maxillodental system at
      various stages of ontogenesis were studied. Sex-specific differences were found
      to augment with age; all the analyzed parameters in boys were superior to those
      in girls at the age when sex-specific factors completely exerted their effects on
      the maxillodental system at the period of permanent teeth occlusion.

PMID- 8754547
TI  - [The effect of smoking on the general somatic and stomatological status of the
      population].

PMID- 8754548
TI  - [Congenital craniofacial pathology].
AB  - The possibility of using compact nonresorbed hydroxyapatite ceramics as synthetic
      bone plastic materials is discussed. Results of follow-up of 11 patients with
      congenital and posttraumatic deformations of the craniofacial skeleton are
      analyzed, to whom hydroxyapatite-based ceramic blocks were implanted for both
      contour plasty and for repair of bone defects. Methods of the operations with
      hydroxyapatite-based implants and titanium devices for fixing bone fragments and
      ceramic blocks are described.

PMID- 8754549
TI  - [Is there still a place for biliointestinal bypass in the treatment of super
      obesity?].

PMID- 8754550
TI  - [Sclerosing adenocarcinomas of the hepatic hilum].
AB  - The authors report their series of 7 adenocarcinomas of the hepatic hilum. Five
      patients with a stage IV tumor underwent palliative surgery while the remaining 2
      patients underwent radical surgery. One patient died and 3 reported postoperative
      complications. Overall survival was 2 years and 6 months: these results can be
      considered satisfactory taking into account the advanced stage and the bad
      prognosis of this type of tumor. The aim of a better quality of life may
      represent a reasonable indication to surgery.

PMID- 8754551
TI  - [Thyroid carcinoma in hyperthyroid syndromes].
AB  - The relationship between hyperthyroidism and carcinoma of the thyroid is still
      uncertain. The incidence of thyroid carcinoma ranges from 0.3 to 16.6%. Between
      1984 and 1994 the Authors observed 9 patients affected with thyroid cancer and
      toxic nodular goiter (4 patients) or Basedow disease (2 patients) or
      scintigraphic evidence of single hyperfunctioning nodule (3 patients). Six out of
      the 9 cases were diagnosed as papillary cancer, while three as follicular cancer.
      A carcinoma was diagnosed before operation in only one case, while in the other 8
      patients, the diagnosis was obtained by histological examination of the specimen.
      Four patients underwent subtotal thyroidectomy, while five patients underwent
      radical lobectomy. All patients are alive and in good health; the average follow
      up was 48 months.

PMID- 8754552
TI  - Popliteal-to-tibial bypass for acute leg ischemia complicating aortic
      reconstruction.
AB  - Between 1983 and 1995, elective aortic surgery was performed on 1018 patients for
      aneurysmal (417 cases) or occlusive disease (489 cases), or both (112 cases).
      Intraoperative acute popliteal occlusion, despite of aortic graft patency,
      developed in 2 patients due to distal embolization (0.19%) and in 5 patients
      secondary to acute popliteal trifurcation thrombosis (0.49%). Preoperative ankle
      index was 0.46 +/- 0.12, but intraoperatively it went down to zero; distal
      popliteal occlusion was confirmed by intraoperative arteriography. A balloon
      catheter embolectomy was performed in two patients. Distal bypass from popliteal
      artery above knee (1) and below knee (3) to the posterior tibial artery was
      implanted in four patients using reversed autogenous saphenous vein. In one
      patient, revascularization was not feasible because of diffuse calcified
      obstructive disease of leg arteries. Reoperations resulted in a satisfactory
      outcome in 6 out of 7 patients (85.7%). The patient, in which revascularization
      was not possible, was submitted to major amputation. In the four popliteal-to
      tibial bypasses evaluated through a follow up period of 43 months, graft patency
      was 75% and limb salvage rate was 100%. Instead of amputation, popliteal-to
      tibial bypass is a useful treatment for acute in situ thrombosis of popliteal
      trifurcation following aorto-iliac reconstruction.

PMID- 8754553
TI  - [Intestinal lymphangiectasis in adults].
AB  - Although rarely, several conditions may cause malabsorption through lymphatic
      obstruction. Primary lymphangiectasia, a genetically determined disease
      characterized by diarrhoea, steatorrhoea and protein-losing enteropathy, is one
      of these conditions. The Authors report their experience in three cases of small
      bowel lymphangiectasia occurring in adults and discuss diagnostic and therapeutic
      problems of the disease.

PMID- 8754554
TI  - [Abdominal vascular and colonic pathology: the timing of combined treatment].
AB  - The authors report their experience with the combined treatment of concomitant
      vascular and colic pathology. After a wide review of the literature, the
      different surgical approaches to reduce the risks of mortality, morbidity and
      bacterial contamination of the vascular prosthesis are discussed.

PMID- 8754555
TI  - [Meigs' syndrome. A case report].
AB  - The authors report on a case of Meigs' syndrome in a patient admitted with
      vomiting, abdominal pain, peritoneal and right pleural effusion, increased serum
      levels of CA 125. Surgical excision was successful.

PMID- 8754556
TI  - [Our experience in the surgical treatment of pharyngoesophageal diverticula].
AB  - The authors review a consecutive series of 7 pharyngo-oesophageal diverticula
      surgically treated from 1979 to 1994. In their opinion, surgery of diverticula to
      be effective must be preceded by dynamic and functional studies to outline the
      motor impairment often associated. Surgical indications and the different
      surgical techniques are also emphasized.

PMID- 8754557
TI  - [Skeletization of the inferior mesenteric artery in colorectal surgery. Current
      considerations].
AB  - Anastomotic dehiscence after colon resection is the most frequent complication in
      colon surgery and the main cause of post-operative death. In the light of
      anatomical peculiarities of the blood supply to the rectum, it would appear that
      in atherosclerotic patients with impairment of hypogastric arteries (80% in
      authors' series out of 200 atherosclerotic subjects) inferior mesenteric artery
      ligature, determining vascularization of the rectal ampulla by the distal vessels
      alone, results in an insufficient supply in case of colo-rectal anastomosis. A
      series of 15 cases of cancer of the left and sigmoid colon, treated with left
      hemicolectomy, preservation and peeling of the inferior mesenteric artery, is
      reported. In the follow-up ranging from 6 months to 5 years, no anastomotic
      dehiscence was observed and only one case (7.5%) presented hepatic recurrence
      after two years. The other patients are all alive and disease free.

PMID- 8754558
TI  - [The preoperative staging of rectal cancer. A comparative assessment between
      endorectal echography and pelvic CT].
AB  - The authors report a comparative study between endorectal ultrasonography (EU)
      and computed tomography (CT) in the preoperative assessment of 94 patients with
      rectal cancer. In evaluating the depth of wall penetration of rectal tumors EUS
      and CT offered good results: EUS confirmed a clear superiority with overall
      accuracy of 88.4% versus 80% of CT. On the contrary, in detecting lymph node
      metastases both techniques had poor results obtaining a correct diagnosis in
      75.6% of the cases with EUS and in 69.4% of the cases with CT. In conclusion, the
      authors believe that EUS and CT may by very useful in the study of tumor
      penetration of the rectal wall; while in the study of lymph node involvement new
      techniques for a more accurate diagnosis are needed.

PMID- 8754559
TI  - [Breast reconstruction with the use of tissue expanders in outpatient treatment].

PMID- 8754560
TI  - [The laparoscopic approach: a technical note].
AB  - The authors report their laparoscopic access technique. It has to be considered a
      variation of the classical closed technique, with the introduction of the Veress
      needle and the first trocar directly at the level of the fascia which is kept in
      traction by two Kochers.

PMID- 8754561
TI  - Surgical research in orthotopic liver transplantation: experiences in the pig
      model.
AB  - Since the very beginning of liver transplantation in humans, research in animals
      has had close relationship with clinical practice. Results obtained in animals
      have been transferred to the clinics and problems borne in the clinics have been
      addressed again in animals for to be answered clearly. In this review the authors
      report their experience of transplantation in the pig model and discuss the
      significance of a team cooperation in the laboratory as a preparatory step for
      clinical practice.

PMID- 8754562
TI  - Commentary on Berryman HE, Smith OC, Symes SA. Diameter of cranial gunshot wounds
      as a function of bullet caliber. J Forensic Sci 1995 Sept; 40(5): 751-4.

PMID- 8754563
TI  - Further commentary on Berryman HE, Smith OC, Symes SA. Diameter of cranial
      gunshot wounds as a function of bullet caliber J Forensic Sci 1995 Sept;40(5):
      751-4.

PMID- 8754564
TI  - Commentary on Rosenbluth W, Hicks L. Evaluating low-speed rear-end impact
      severity and resultant occupant stress parameters J Forensic Sci, 1994;39 (6,
      Nov): 1393-1424.

PMID- 8754565
TI  - Validation of probe EFD52 (D17S26) for forensic DNA analysis.
AB  - Validation studies that meet TWGDAM (The Working Group on DNA Analysis Methods)
      and CAC (California Association of Criminalists) guidelines for RFLP (restriction
      fragment length polymorphism) analysis were performed with the DNA probe EFD52
      (D17S26). These studies demonstrate that the probe EFD52 is suitable for forensic
      casework. No unexpected DNA banding patterns were obtained from controlled
      studies examining various tissues, sample consistency over many gels, mixtures of
      body fluids, various substrates, various contaminants and non-human DNA sources.
      Of all the animal DNAs tested, only one higher primate yielded a single band to
      EFD52 hybridization. The sensitivity of EFD52 was shown to be comparable to that
      of other forensic probes. Population frequency distribution tables were prepared
      from over 4000 alleles and two-locus studies were conducted on nine forensically
      useful probes. Black, White, Hispanic and Lumbee Indian populations were found to
      be in Hardy-Weinberg and linkage equilibrium. Comparisons between victim blood
      standards and epithelial fractions of mixed strains from sexual assault cases
      were used to demonstrate the robustness of the EFD52 probe in forensic casework.

PMID- 8754566
TI  - Chemiluminescent detection of RFLP patterns in forensic DNA analysis.
AB  - DNA testing by restriction fragment length polymorphism (RFLP) analysis is an
      extremely important technique used in forensic science laboratories. While RFLP
      testing is a highly informative method, it traditionally has had several
      disadvantages. It is time consuming and involves work with radioactive
      phosphorous. A detection method that is faster and safer than isotopic detection
      is presented. Various membranes, fixation methods and transfer procedures were
      evaluated for DNA retention and sensitivity using alkaline phosphatase conjugated
      oligonucleotide probes and a chemiluminescent substrate. Blood samples and
      evidentiary material from forensic casework were analyzed by both
      chemiluminescent and isotopic detection. Results of each method were compared for
      pattern appearance, band size, and composite profile frequency. The
      chemiluminescent system had very good sensitivity, detecting 3-25 ng K562 DNA.
      Most patterns developed by both methods appeared the same. The variation observed
      between band sizes and frequency estimates generated by each method was as
      expected for an inter-gel comparison. The chemiluminescent detection procedure
      described here is suitable for use in forensic casework.

PMID- 8754567
TI  - Allelic ladder characterization of the short tandem repeat polymorphism in intron
      6 of the lipoprotein lipase gene and its application in an Austrian Caucasian
      population study.
AB  - The short tandem repeat (STR) polymorphism HumLPL (TTTA)n, which is located in
      intron 6 of the lipoprotein lipase gene, was investigated by AMPFLP
      (amplification fragment length polymorphism)-technique using an allelic ladder
      consisting of amplified alleles of this locus as a standard size marker. The
      allelic ladder was prepared by pooling equal concentrations of six separate
      alleles, which were identified by their different electrophoretic mobility in
      native polyacrylamide gel, eluted and subsequently amplified. Sequence analysis
      of the ladder alleles and allele 7, which is not included in the ladder, showed a
      regular repeat structure with 7 and 9 to 14 repetitions of the core repeat. The
      allelic ladder was employed in the analysis of the genotypes of 550 unrelated
      Caucasoids of Austria. No new alleles were found. The population investigated
      showed no deviation from Hardy-Weinberg equilibrium (P = 0.195).

PMID- 8754568
TI  - Validation of multiplex polymorphic STR amplification sets developed for personal
      identification applications.
AB  - Polymorphic short tandem repeat (STR) loci, which typically consist of variations
      in the number of 3-7 base pair repeats present at a site, provide an effective
      means of personal identification. Typing can be accomplished by amplification of
      genomic DNA using the polymerase chain reaction (PCR) and locus-specific primers,
      separation of amplified alleles using gel electrophoresis and their display using
      silver staining or fluorescent detection. Primers for several STR loci can be
      combined in a single multiplex reaction so typing of multiple loci can be
      accomplished rapidly and with less DNA than required if each locus were analyzed
      separately. Before such muliplex systems are used in forensic or paternity
      applications, it is desirable that they undergo testing for their reliability.
      This study evaluates the performance of two STR triplex systems, one containing
      the loci HUMCSF1PO, HUMTPOX, and HUMTH01, and the other containing HUMHPRTB,
      HUMFESFPS, and HUMVWFA31. Protocols for amplification of these two triplexes, and
      their corresponding monoplexes, were evaluated for sensitivity of detection,
      resistance to changes in the annealing temperature of the amplification protocol,
      and the ability to identify the minority contributor in amplification of mixed
      samples. In addition, five laboratories determined the alleles of twenty DNA
      samples, each extracted by one of four different extraction methods. The results
      illustrate that the two STR triplex systems and the monoplex systems contained
      within them can be used with as little as 0.25 ng of DNA template. Both triplexes
      amplified with 100% success using the Perkin Elmer Model 480 thermal cycler. With
      the GeneAmp 9600 System, the CTT triplex amplified with 100% success and the HFv
      triplex in 95.6% of attempts. These experiments meet many requirements for use in
      validation of DNA typing systems for forensic cases and paternity identification.

PMID- 8754569
TI  - Extent of heterogeneity in mitochondrial DNA of ethnic Asian populations.
AB  - Variation in the mitochondrial DNA (mtDNA) control region as detected by sequence
      specific oligonucleotide (SSO) probes is described for 993 individuals in 11
      ethnic Asian populations. Estimates of diversity for mtDNA types exceed 0.94 in
      all populations, while 53% of the 255 types that were observed occur only once.
      Of 96 shared types, four occur at frequencies of greater than 10% but less than
      17% in any one population. There is statistically significant heterogeneity among
      these 11 populations, however, an analysis of variance incorporating genetic
      distances between types shows that at least 95% of the variation present in the
      total sample is attributable to within-population diversity, while only 5% is due
      to between-population differences. Overall, heterogeneity with respect to mtDNA
      SSO types is grossly correlated with geographic distance between populations; the
      most extreme heterogeneity was observed between populations from East Asia and
      populations from West Asia. With respect to population genetics, the control
      region of mtDNA exhibits satisfactory qualities as a DNA typing locus.

PMID- 8754570
TI  - Evaluating DNA profile evidence when the suspect is identified through a database
      search.
AB  - The paper is concerned with the strength of DNA evidence when a suspect is
      identified via a search through a database of the DNA profiles of known
      individuals. Consideration of the appropriate likelihood ratio shows that in this
      setting the DNA evidence is (slightly) stronger than when a suspect is identified
      by other means, subsequently profiled, and found to match. The recommendation of
      the 1992 report of the US National Research Council that DNA evidence that is
      used to identify the suspect should not be presented at trial thus seems
      unnecessarily conservative. The widely held view that DNA evidence is weaker when
      it results from a database search seems to be based on a rationale that leads to
      absurd conclusions in some examples. Moreover, this view is inconsistent with the
      principle, which enjoys substantial support, that evidential weight should be
      measured by likelihood ratios. The strength of DNA evidence is shown also to be
      slightly increased for other forms of search procedure. While the DNA evidence is
      stronger after a database search, the overall case against the suspect may not
      be, and the problems of incorporating the DNA with the non-DNA evidence can be
      particularly important in such cases.

PMID- 8754571
TI  - Postmortem stability of cocaine and cocaethylene in blood and tissues of humans
      and rabbits.
AB  - A study was conducted to examine the postmortem stability of cocaine and
      cocaethylene in rabbit blood and tissues, and to determine whether cocaethylene
      is produced in decomposed human specimens containing cocaine and endogenous
      ethanol. Heart blood, liver, brain and femoral muscle taken from rabbits 20 min
      after oral administration of 20 mg/kg cocaine together with 2 g/kg ethanol were
      kept at 20-25 degrees C for 5 days. Cocaine and cocaethylene concentrations were
      in the order brain > liver > muscle > blood, and showed very large intersubject
      variations at the time of death. Cocaine was degraded rapidly in the blood and
      liver. However, 12.0 +/- 8.5% and 26.2% +/- 19.4% of the original cocaine was
      still detectable in the brain and muscle, respectively. Cocaethylene was degraded
      more slowly than cocaine in all of the specimens. The pH of the blood remained
      around 7.4 during a 5-day period; all the other specimens showed pH values of 6.2
      6.7 on and after the first day postmortem. When 10,000 ng/g cocaine was incubated
      with decomposed human blood, liver, brain and muscle homogenates containing 0.29
      0.60 mg/g endogenous ethanol at 20-25 degrees C and 37 degrees C, no change in
      cocaine concentration was observed during the study period of 24 h, and no
      cocaethylene was detected. The pH values of the homogenates were within the range
      4.2 to 5.2 at the beginning of the experiment. It was found that: 1) cocaethylene
      was more stable in postmortem specimens than cocaine; 2) muscle as well as brain
      was specimen of choice for detecting cocaine and cocaethylene postmortem; 3)
      cocaine was resistant to decomposition under acidic conditions; and 4)
      putrefactive bacteria had no ability to produce cocaethylene even in the presence
      of cocaine and endogenous ethanol.

PMID- 8754573
TI  - Caliber estimation from cranial entrance defect measurements.
AB  - Caliber estimation from entrance defects has long been rejected by forensic
      scientists. This appears to be a consequence of soft tissue perspective of
      forensic pathologists. This study examined the relation between caliber and
      cranial entrance defects and maximum cranial thickness. The calibers considered
      in this inquiry were .22, .25, .32, and .38. The sample consisted of 73 specimens
      obtained at autopsy (thirty-seven of .22 caliber, five of .25, six of .32, and
      twenty-five of .38). To test the strength of the relation between caliber,
      minimum diameter, and maximum thickness Pearson correlation coefficients were
      conducted. The strongest relationship was observed between caliber and minimum
      diameter. A relationship between minimum diameter and maximum thickness was also
      observed. To test the null hypothesis that the mean minimum diameter is not
      significantly different between calibers an analysis of variance procedure was
      performed. The ANOVA yielded a strong relationship between dependent variable
      minimum diameter and caliber. Multiple regression analysis measuring the
      association between minimum diameter, caliber, and maximum thickness was also
      conducted. The Pr > F .0001 suggests that the overall model is significant.
      Discriminant functions and canonical variables were obtained. Classification was
      first performed by using two values small and large calibers. The large caliber
      group consisted of .38, while the small caliber group included .22, .25, and .32.
      The correct classification rate using crossvalidation for large caliber is
      86.96%, and 93.33% for the group small caliber. A narrower classification was
      also performed by using three values, .23 caliber (.22 and .25 calibers grouped),
      .32, and .38 as the criterion variable groups also using minimum diameter and
      maximum thickness as predictors. The correct classification rate using
      crossvalidation is 82.02% for .23 caliber, 73.94% for .38 caliber, and 16.67% for
      .32 caliber defects. The discriminant functions can be used with appropriate
      caution to classify observations into groups defined by caliber using minimum
      diameter and maximum thickness as the predictors. Caution is suggested when
      attempting to estimate caliber from defects that are not produced from the
      perpendicular entrance of a bullet.

PMID- 8754572
TI  - The incidence of acute cocaine or methamphetamine intoxication in deaths due to
      ruptured cerebral (berry) aneurysms.
AB  - Acute intoxication with either cocaine or methamphetamine may contribute to
      formation and rupture of a berry aneurysm by causing transient hypertension and
      tachycardia. We report the results of a retrospective study to determine the
      incidence of acute cocaine or methamphetamine intoxication in deaths due to
      ruptured berry aneurysm in our jurisdictions. We reviewed all deaths from
      ruptured cerebral aneurysms that fell within our jurisdictions during the seven
      years from 1 January 1987 to 31 December 1993 and found 83 cases. The mechanism
      of death invariably involved subarachnoid hemorrhage, although some cases also
      had intracerebral hemorrhage. A history of drug abuse was found in 13 cases.
      Toxicological analysis was performed in 39 cases. Of these methamphetamine was
      detected in six cases and cocaine in three cases--an incidence of 21%. (In one
      case both methamphetamine and cocaine were detected). The incidence of acute
      cocaine intoxication in all autopsies in Jefferson County was 13.6%. The
      incidence of methamphetamine intoxication in all autopsies in San Diego County
      was 4.9%. Although the exact mechanism by which berry aneurysms form remains
      undetermined, research indicates that propagation and rupture of the aneurysm are
      aggravated by hypertension and tachycardia, both of which are pharmacologic side
      effects of cocaine and methamphetamine. Based on the preponderance of
      methamphetamine associated with deaths due to ruptured berry aneurysms it appears
      that methamphetamine is more toxic than cocaine, perhaps owing to the longer half
      life of methamphetamine.

PMID- 8754575
TI  - Disturbances in the soil: finding buried bodies and other evidence using ground
      penetrating radar.
AB  - Ground penetrating radar (GPR) is an efficient and effective means to search for
      buried evidence, whether it be a clandestine grave, formal burial, or certain
      missing articles from a crime scene. The procedures for GPR used by the U.S. Army
      Central Identification Laboratory, Hawaii (CILHI), are the result of several
      years of experimentation on a variety of ground surfaces in Hawaii, Southeast
      Asia and the mainland U.S. This remote sensing method does not usually provide
      direct information that there is a body or other specific object beneath the
      ground. Most of the time the GPR has been used to determine where a target object
      is not located. The key feature of GPR is that it can detect recent changes in
      shallow soil conditions caused by the disturbance of soil and the intrusion of
      different material. Using the methods described here, the investigator should be
      able to determine the precise metric grid coordinates for a subsurface
      disturbance, as well as the approximate size, the general shape, and the depth of
      the buried material. Success will vary with soil conditions. The conditions
      suitable or not practical for using GPR are summarized. This remote sensing
      technology can have wider use in crime scene investigations due to the recent
      introduction of more user-friendly software and more portable hardware.

PMID- 8754574
TI  - Dangerous delusional misidentification and homicide.
AB  - A case involving a delusional misidentification syndrome associated with homicide
      is presented. The anglophonic literature concerning delusional misidentification
      and homicide is reviewed. Delusional misidentification may be a risk factor for
      potential violence toward others, including homicide of a delusionally
      misidentified person.

PMID- 8754576
TI  - Efficient and reliable PCR-based detection of the ABO blood group alleles:
      genotyping on stamps and other biological evidence samples.
AB  - PCR-based ABO genotyping was established using restriction enzyme digestion
      followed by horizontal polyacrylamide gel electrophoresis and silver staining.
      The method described here is fast, with results obtained within hours, not days,
      it obviates the need for radioisotopes and can be performed with 1-2 ng of
      extracted genomic DNA. ABO blood group determination was successful in various
      types of biological materials of forensic interest such as bloodstains, vaginal
      swabs, cigarette butts, and hair roots. Moreover, after preincubation in
      distilled water, DNA (2-8 ng) was extracted from 12 up to 10-years-old stamps and
      was correctly typed at the ABO locus. The results presented here indicate that
      the PCR-based ABO genotyping is a fast, sensitive, reliable, and economic method
      providing blood group determination in DNA from a variety of different types of
      specimens. It can provide determination from specimens of limited amount and/or
      with partially degraded DNA as well. Therefore, it is very useful for first-step
      suspect screening as well as in forensic research for the analysis of biological
      evidence.

PMID- 8754577
TI  - Epidermal cells on stubs used for detection of GSR with SEM-EDX: analysis of DNA
      polymorphisms.
AB  - DNA from epidermal cells attached to the adhesive tape of stubs employed to
      collect and identify gunshot residue (GSR) with scanning electron microscope
      (SEM) was extracted, amplified with PCR and typed. The method allowed
      identification of specimens when attribution to a definite person was uncertain.
      These results also suggest that adhesive tape could be used as a non invasive
      method for obtaining biological material suitable for DNA analysis from the skin
      surface.

PMID- 8754578
TI  - Multiplex amplification and typing procedure for the loci D1S80 and amelogenin.
AB  - A method has been developed that enables multiplex amplification and simultaneous
      typing of the loci D1S80 and amelogenin using discontinuous polyacrylamide gel
      electrophoresis and silver staining. The protocol is sensitive, simple, rapid,
      and relatively inexpensive. The results of the multiplex analysis of the D1S80
      and amelogenin loci were comparable to those obtained when each locus was
      analyzed individually. A small validation study was undertaken to evaluate the
      forensic applicability of this multiplex system. The data demonstrate that DNA
      exposed to a variety of environmental insults yields reliable multiplex typing
      results.

PMID- 8754579
TI  - Genetic polymorphism of the inter-alpha-trypsin inhibitor (ITI) in Cadiz
      Province, Southern Spain.
AB  - The results of a study of Inter-Alpha-Trypsin Inhibitor (ITI) polymorphism in 281
      blood samples are reported in this paper. These samples were taken from healthy
      individuals of both sexes, unrelated and resident in the Province of Cadiz. The
      frequency of ITI*1 was 0.617 and of ITI*2 was 0.383. The probability of exclusion
      in paternity testing was 0.18.

PMID- 8754580
TI  - Hungarian population data on seven PCR-based loci.
AB  - Hungarian population data for the loci LDLR, GYPA, HBGG, D7S8, Gc, HLA-DQA1, and
      D1S80 were generated. The genotype frequency distributions for the loci do not
      deviate from Hardy Weinberg expectations. Furthermore, there was little evidence
      for departures from expectations of independence between the loci. Using a test
      for homogeneity all the loci were similar between two Hungarian population
      samples and only the HLA-DQA1 locus was statistically different between
      Hungarians and US Caucasians. There generally would be little forensic
      differences, whether a Hungarian or a US Caucasian database was used, for
      estimating multiple locus profile frequencies for the seven PCR-based loci.

PMID- 8754581
TI  - Paternity exclusion by DNA markers: effects of paternal mutations.
AB  - In parentage testing when one parent is excluded, the distribution of the number
      of loci showing exclusion due to mutations of the transmitting alleles is
      derived, and it is contrasted with the expected distribution when the exclusion
      is caused by nonpaternity. This theory is applied to allele frequency data on
      short tandem repeat loci scored by PCR analysis, and VNTR data scored by Southern
      blot RFLP analysis that are commonly used in paternity analysis. For such
      hypervariable loci, wrongly accused males should generally be excluded based two
      or more loci, while a true father is unlikely to be excluded based on multiple
      loci due to mutations of paternal alleles. Thus, when these DNA markers are used
      for parentage analysis, the decision to infer non-paternity based on exclusions
      at two or more loci has a statistical support. Our approach places a reduced
      weight on the combined exclusion probability. Even with this reduced power of
      exclusion, the probability of exclusion based on combined tests on STR and VNTR
      loci is sufficiently large to resolve most paternity dispute cases in general
      populations.

PMID- 8754582
TI  - The wrong urn: commingling of cremains in mortuary practices.
AB  - Personal identification of human skeletal remains altered by the heat of
      crematory furnaces in modern mortuaries may be complicated by the presence of
      more than a single individual in a sample. When identification of cremains of
      neonates and young children is required in legal disputes, as in cases where
      relatives suspect that a funeral establishment has presented them with the ashes
      of another individual, the forensic anthropologist may be consulted by their
      legal representative. Problems to be considered in personal identification of
      cremated bodies are (1) presence or absence of commingled remains in a sample;
      (2) identification of one or more individuals present. Methods used in sorting
      and identifying neonate, infant and pre-adolescent remains include reconstruction
      of stature in situations where long bone diaphyses are preserved, as this may
      provide evidence of age at time of death, and assessment of dental crown
      development of unerupted and erupted deciduous teeth also for age determination.
      These procedures were used in the case reported here concerning mortuary
      practices of a funeral home and a family claiming that they were presented with
      the cremains of an adult and not those of their 15-hour-old daughter.

PMID- 8754583
TI  - Probable torticollis revealed in decapitated skull.
AB  - The skeletal features of a moderately decomposed decapitated head recovered in
      1993 are consistent with torticollis (wryneck) and inconsistent with other
      possible syndromes. Asymmetries of the face, cranial vault, mandible, and
      cervical vertebrae closely resemble published cases of paleopathological and
      recent torticollis. The laterally directed left occipital condyle and
      articulation of the basicranium and cervical vertebrae indicate that the head was
      tipped toward the left shoulder. Right-left asymmetries of areas of muscular
      attachments are compatible with a leftward head deviation. Mild arthritis of the
      atlantal-occipital and intervertebral joints, clinoid bridging, and thickening of
      the inner table of the frontal squamosa may not be related to the possible
      torticollis. The postural deviations of the head and neck may aid in the
      identification of this homicide victim, as did skeletal evidence to torticollis
      in an earlier case from Britain.

PMID- 8754584
TI  - Hair and fiber transfer in an abduction case--evidence from different levels of
      trace evidence transfer.
AB  - Levels of trace evidence transfer were examined in a casework context. A girl was
      allegedly abducted in a car and rape attempted by the accused, who denied any
      contact with the victim. Clothing worn by the victim and the accused, and the
      covers from the front seats of the car, were analyzed for trace evidence. Three
      types of corresponding fibers and four possible pathways of transfer were
      identified. Synthetic fibers similar to those composing the car seat covers were
      located on the victim's clothing, consistent with direct transfer. Secondary
      transfer was indicated by dyed brown human head-type hairs (possibly originating
      from the accused's wife) located on the seat covers and on the victim's clothing.
      Secondary and possibly tertiary transfer was indicated by pink synthetic material
      and associated fibers (possibly originating from the victim's mother) located on
      the victim's clothing, a car seat cover and the accused's clothing. Light
      microscopy, comparison microscopy, and cross-sectioning techniques were used. The
      multiple fiber matches and the differing pathways and levels of transfer
      increased the strength of the association between the accused and the victim.
      After the fiber evidence was led at the trial, the accused pleaded guilty,
      thereby affirming the value of secondary transfer evidence.

PMID- 8754585
TI  - The recovery of seminal components and DNA from the vagina of a homicide victim
      34 days postmortem.
AB  - The body of an 18-year-old female was discovered in a gravel pit in Northern
      Maine. Investigation determined the body to be that of a woman who had
      disappeared from the Bangor, Maine area 34 days earlier. Laboratory examination
      revealed the presence of intact spermatozoa, P30 and restriction fragment length
      polymorphism (RFLP) typable DNA on a vaginal swab and smear slide collected at
      autopsy.

PMID- 8754586
TI  - Identifying the order in which blood and handwriting were deposited on a
      document.
AB  - As a consequence of a murder investigation, it became necessary to determine
      whether blood was present on a note prior to the handwritten entries being
      deposited on the paper. A simple and non-destructive technique using a profile
      projector was developed to allow such a determination to be made and
      photographed.

PMID- 8754587
TI  - Pseudonecrophilia following spousal homicide.
AB  - A case of pseudonecrophilia by a 26-year-old male following the multiple stabbing
      death of his wife is reported. Intoxicated with alcohol at the time, the man
      positioned the corpse of his spouse to facilitate vaginal intercourse with her in
      the lithotomy position while he viewed soft core pornography on television.
      Clinical interview, a review of history, and psychological testing revealed
      diagnoses of antisocial personality disorder and major depression (DSM-IV,
      American Psychiatric Association 1994). There was no evidence of psychosis, but
      some indices of mild neuropsychological impairment. The motivations for this rare
      case of pseudonecrophilia are discussed in relation to extant research, and a
      cautionary note is offered in assuming sexual causality in the investigation of
      homicides when there is evidence of sexual arousal or activity by the
      perpetrator.

PMID- 8754588
TI  - Chasing the casing: a 38 Special suicide.
AB  - Multiple self-inflicted gunshot wounds of the head are uncommon. Detailed
      history, scene investigation, autopsy findings, consideration of ballistics, and
      evidentiary proceedings are necessary to determine the manner of death in these
      cases. This report involves a pattern of atypical, self-inflicted bullet wounds
      of the head of a 26-year-old male. Investigation confirmed that a single
      eyewitness and several earwitnesses reported a single discharge of a firearm. The
      eyewitness testified that the decedent singly discharged a Smith & Wesson
      revolver, caliber .38 Special, to the right side of his head after interposing
      several objects between the muzzle and his skin immediately prior to discharge.
      He was declared brain dead two days later. At necropsy two contiguous atypical
      entry wounds were present in the right preauricular temple. The inferior wound
      was interpreted to be a near contact wound. The gray metal slug fragmented,
      creating separate tracks to the right maxillary sinus and the mid left posterior
      cerebrum, respectively. The larger, atypical wound of entry was associated with
      passage of the projectile through the right temporalis muscle and squamous
      temporal bone. The projectile, consisting of a slightly distorted empty metallic
      cartridge case containing a "live" primer, was recovered from its point of final
      lodgment in the right temporal lobe. The literature addressing paired entry
      wounds following single discharge of the firearm with interposed targets is
      relatively sparse. Cases reporting multiple bullet wounds involving suicide are
      only sporadically reported. This report summarizes the investigative findings
      supporting the determination of the manner of death and revealing the interesting
      origin of the "misplaced" casing.

PMID- 8754589
TI  - Methamphetamine identification in four forensic cases.
AB  - Specimens that tested positive for amphetamines by immunoassay were confirmed by
      mass spectrometry. The absence of detectable d-amphetamine (limit of detection at
      50 ng/mL) with a positive methamphetamine prompted further testing by chiral
      derivatization. This data demonstrates that d-amphetamine need not be present in
      methamphetamine positive cases.

PMID- 8754590
TI  - A new biological test for suicidality?

PMID- 8754591
TI  - The use of placebos in psychiatry: a response to the draft document prepared by
      the Tri-Council Working Group. Canadian College of Neuropsychopharmacology.
AB  - This article is a position paper of the Canadian College of
      Neuropsychopharmacology (CCNP). It was approved unanimously at a meeting of the
      CCNP Council on June 2, 1996, and at the CCNP Annual General Business Meeting on
      June 4, 1996.

PMID- 8754592
TI  - Artificial neural networks: a prospective tool for the analysis of psychiatric
      disorders.
AB  - Artificial neural networks are computer simulations of biological parallel
      distributed processing systems. They are able to undertake complex pattern
      recognition tasks, including diagnostic classification, prediction of disease
      onset and prognosis, and identification of determinants of clinical decisions.
      These capabilities have been utilized in general medicine, but as yet there has
      been little application of artificial neural networks in psychiatric research.
      Artificial neural networks can also be used to create models of brain function,
      providing a paradigm for cognition and the organization of neural systems that
      demonstrates how changes at the cellular level can affect information processing.
      These models are able to encompass both the biological and the behavioral
      dimensions of psychiatric disorders.

PMID- 8754593
TI  - Choline-containing compounds detected by proton magnetic resonance spectroscopy
      in the basal ganglia in bipolar disorder.
AB  - Choline-containing compounds (Cho) were examined by proton magnetic resonance
      spectroscopy (1H-MRS) in the left subcortical region, including basal ganglia, in
      19 euthymic patients with bipolar disorder and 19 age-matched normal controls.
      Ten of the patients were treated with lithium; the remaining 9 were not treated
      with lithium for at least 30 d. The Cho to creatine + phosphocreatine (Cr) peak
      ratio in the bipolar patients (0.75 +/- 0.38 [mean +/- SD]) was higher than that
      in the normal controls (0.52 +/- 0.26, P < 0.05). There was no significant
      difference in the Cho:Cr peak ratio between patients treated with lithium (0.63
      +/- 0.36) and without lithium (0.89 +/- 0.35). These results do not support the
      hypothesis that lithium increases the brain choline-containing compounds, but
      rather imply that membrane breakdown may occur in the basal ganglia of patients
      with bipolar disorder.

PMID- 8754594
TI  - Sexual dysfunction in relapsing-remitting multiple sclerosis: magnetic resonance
      imaging, clinical, and psychological correlates.
AB  - The purpose of this study was to examine the sexual complaints and severity of
      sexual dysfunction in relapsing-remitting multiple sclerosis patients and to
      correlate them with psychological, neurological, and radiological variables.
      Frequency and characteristics of sexual disturbances were reported by 41 multiple
      sclerosis patients (32 females, 9 males; mean age 35.4 +/- 10.2 y). Clinical
      neurologic variables tested were disease duration, exacerbation rate, and
      disability; psychological variables tested were anxiety and depression. All
      patients underwent a brain magnetic resonance imaging (MRI) scan at the time of
      this study. The sexual dysfunction questionnaire included items based on the 3
      phases of human sexual response: loss of libido, excitement (arousal
      difficulties, impotence, premature ejaculation), and anorgasmia. Five males
      (55.5%) and 16 females (50.0%) reported at least 1 sexual disturbance. The most
      frequent dysfunctions were loss of libido (26.8%) and arousal difficulties
      (19.5%). Females rated their difficulties as more severe. Sexual dysfunctions
      correlated with depression, (r = 0.68, P = 0.001). No correlation between MRI
      score and depression was found. Anorgasmia correlated with brain stem and
      pyramidal abnormalities (r = 0.56, P = 0.011; r = 0.56, P = 0.012, respectively).
      The total area of lesions (plaques) on the brain MRI scan also correlated with
      anorgasmia (r = 0.41, P = 0.02). Sexual dysfunctions in multiple sclerosis
      patients are frequent, are mild to moderate in severity, correlate with
      depression and in some cases central nervous system (CNS) demyelinating process,
      and thus may be related either to the psychological impact of this disease or to
      specific organic lesions in the brain.

PMID- 8754595
TI  - Diffuse electroencephalogram slowing in psychiatric patients: a preliminary
      report.
AB  - Diffuse slowing constitutes 40% of all electroencephalogram (EEG) abnormalities
      in psychiatric patients. Correlations have been demonstrated between the degree
      of slowing of the EEG and impairment of functions such as awareness, attention,
      memory, and comprehension. We conducted the current study in order to determine
      whether diffuse EEG slowing in hospitalized psychiatric patients correlated with
      hospitalization indices. Twenty-five patients with diffusely slow EEGs were
      selected for the study, and 25 patients with normal EEGs were matched to these
      subjects. Medical records were reviewed for each patient's diagnosis, length of
      stay, number of medications, and the dosages. Length of stay was significantly
      longer in the slow EEG group. The number of psychotropic medications used and the
      dosages of antipsychotic medications were also significantly higher in the slow
      EEG group. We concluded that the longer length of stay and the increased number
      of medications and dosages in the slow EEG group may be a reflection of increased
      illness severity.

PMID- 8754597
TI  - [Clozapine in a Chinese population].

PMID- 8754598
TI  - Artic medical research in Denmark and Greenland.

PMID- 8754599
TI  - The impact of housing on health: an ecologic study from the Canadian Arctic.
AB  - OBJECTIVES AND METHOD: An ecologic study was conducted to investigate the
      association between housing and health in 49 predominantly Native communities in
      the Northwest Territories (NWT) in the Canadian Arctic, making use of data from a
      housing survey and data relating to physical and social health routinely reported
      to various service delivery agencies. RESULTS: The rate of health centre visits,
      as a measure of morbidity, correlated with most housing and socioeconomic status
      (SES) indicators. Communities with worse housing and SES were found to have a
      higher rate of health centre visits. Using factor analysis, composite housing and
      SES indicators were constructed. Housing was poorly correlated with any of the
      outcome variables, whereas SES was strongly correlated with health centre visits
      and moderately correlated with the occurrence of fires. Communities with worse
      SES were more likely to have a higher rate of health centre visits but the
      opposite effect was observed with fires. When both housing and SES indices were
      included in a multiple regression model, SES was the stronger factor in
      predicting the rate of health centre visits and fires. No significant association
      exists between these variables and the frequency of sentenced admissions.
      CONCLUSIONS: It is possible that improvement in housing quality in the NWT may
      have eliminated much disparity and perhaps removed most obvious illness
      generating housing features. Improved housing through subsidies, however, does
      not alter other components of SES such as education, employment and income. The
      importance of SES in health and social well-being is well known and is
      demonstrated in the NWT as well. This study also shows that ecologic analyses can
      provide relatively quick and useful data for public health policy.

PMID- 8754596
TI  - In vivo analysis of the role of dopamine in stimulant and opiate self
      administration.
AB  - Stimulants and opiates increase synaptic dopamine (DA) transmission in nucleus
      accumbens (NAcc), and this action is thought to underlie the habit-forming
      properties of these and several other abused drugs, Much of the experimental
      support for this idea comes from drug self-administration studies. The fact that
      animals will learn an arbitrary response when it is followed by an intravenous
      cocaine or heroin injection has been taken to suggest that these and other such
      drugs act as potent rewards. It is widely assumed that the resulting increase in
      NAcc levels of DA is what reinforces operant-responding in animals and drug
      seeking in humans. Recent evidence from a variety of sources, however, including
      our group, appears to challenge the validity of this assumption. In this article
      we review some of the findings that have emerged thus far from our in vivo
      electrochemical recording studies. The conclusions suggested by our research are
      discussed in relation to those derived from other lines of evidence.

PMID- 8754600
TI  - Determinants of smoking behaviour in random samples of Greenlandic and Danish
      women 20-39 years of age.
AB  - BACKGROUND: The prevalence of smoking among young women is of particular concern
      in most countries as it does not decline as in men. We studied smoking behaviour
      in Greenlandic and Danish women over a 2 year period to provide information on
      the social and behavioural determinants of smoking in women. METHODS: In 1986,
      samples of 800 women aged 20-39 years were drawn at random from Nuuk/Godthab
      (Greenland) and Nykobing Falster (Denmark). A total of 586 and 661 women were
      interviewed in Greenland and Denmark, respectively. In 1988, new random samples
      of 150 women were drawn from the same areas. Totally, 129 Greenlandic and 126
      Danish women were included in this study. In 1987, a sample of 732 women aged 20
      49 years from Copenhagen was randomly drawn from the computerized Central
      Population Register. Of these, 623 women completed a questionnaire. RESULTS:
      Smoking behaviour was almost the same among women in Nykobing Falster and
      Copenhagen (54% smoked) while a significantly higher percentage of smokers was
      observed among women in Greenland (88% smoked). Heavy smoking was most prevalent
      among Danish women and associated with early debut of smoking. Among Danish
      women, smoking was associated with use of oral contraceptives, early age at first
      intercourse, and multiple sexual partners. In Greenland, smoking was associated
      with early sexual debut and multiple sexual partners. In an extended analysis on
      a subgroup of Danish women, smoking was also associated with low education and
      infrequent intake of vegetables. The study showed no development in smoking
      behaviour in any age group over the two year period between the two studies,
      neither in Nykobing Falster nor in Nuuk. CONCLUSION: The high prevalence of
      moderate smoking among women in Greenland suggests that broad anti-smoking
      initiatives are urgently needed. The high prevalence of heavy smoking and a
      social gradient among Danish women may indicate that a strategy focusing on
      restrictions of smoking may be more relevant than merely continuing a pure anti
      smoking information strategy.

PMID- 8754601
TI  - Varying mercury exposure with varying food source in a James Bay Cree community.
AB  - James Bay Quebec Crees are exposed to methylmercury (MM) through fish
      consumption. Hair mercury concentrations were measured in women of child-bearing
      age and men and women 40 years of age and above in a small Cree community of
      James Bay (with traditionally low exposure to MM) before and after fishing
      expeditions to inland lakes where fish were contaminated with methylmercury.
      Median hair mercury concentrations in persons 40 years and above increased from
      4.1 mg/kg to 9.9 mg/kg and the highest value from 17.4 to 47.2 mg/kg. A similar
      increase was seen after a second fishing expedition where the median hair
      concentration increased from 3.4 mg/kg to 7.2 mg/kg and the highest value from
      17.7 to 49.9 mg/kg. Populations with traditionally low exposure to MM can become
      highly exposed with changes in sources or quantities of fish consumed.

PMID- 8754602
TI  - Blood serum analyses in population studies: parallel analyses and degree of
      agreement in a Norwegian-Russian co-project. The Svalbard Study.
AB  - In a survey of more than 300 russian coal workers living on Svalbard, parallel
      laboratory analyses of gamma-glutamyltransferase, serum total cholesterol, high
      density lipoprotein, and triglycerides were performed in Tromso, Norway and in
      Archangelsk, Russia. Mean values for gamma-glutamyltransferase and serum total
      cholesterol were significantly higher in Tromso than in Archangelsk while mean
      values of triglycerides and high density lipoproteins were significantly lower in
      Tromso than in Archangelsk. Linear regression plots revealed both systematical
      and arbitrary differences between the two laboratories. Because no "true"
      standards were available, we were unable to assess the accuracy of laboratory
      results. We conclude that laboratory measurements from Norway and Russia are not
      directly comparable. Future research programs between the two laboratories should
      attempt to include calibrated standards of test serum from which to identify
      sources of variation. Alternatively, the serum tests should always only be
      analyzed at one site.

PMID- 8754604
TI  - The health program of Barents Euroarctic Region 1996. Working Group on Health.

PMID- 8754603
TI  - Trends in the concentrations of mercury, copper, zinc and selenium in inhabitants
      of north-eastern Finnish Lapland in 1982-1991. A pilot study.
AB  - The heavy industry on the Murmansk region in Russia is releasing huge amounts of
      waste into the air, including heavy metals and sulphur compounds. To investigate
      the temporal trend in exposure to certain heavy metals among the inhabitants of
      north-eastern Finland, a pilot study was carried out involving serum and hair
      samples from group of 11 persons monitored in Ivalo in 1982 and 1991. A further 6
      persons residing near the Russian border in Nellim and 10 adults and 2 children
      residing in the Sevettijarvi-Naatamo area also participated in 1991. In addition,
      serum and hair samples were also obtained from controls residing in the Helsinki
      area. Total mercury content, determined by flow injection analysis and the
      amalgam system, pointed to a decrease in concentrations in the hair of
      inhabitants of Ivalo, whereas mercury concentrations were found to be higher in
      those residing near the Russian border. The mercury concentrations in the hair of
      northern inhabitants were about 4 times greater than those in the hair of the
      people from southern Finland on average. No trend towards an increase or decrease
      was found in copper and zinc concentrations in hair and serum as determined by
      atomic absorption spectrometry in employing the flame technique. Selenium has
      been thought to act as an antagonist to the heavy metal mercury. The addition of
      selenium to fertilisers began in Finland in 1984, but such fertilisers have not
      been used widely in Lapland. Selenium concentrations, determined by flameless
      atomic absorption spectrometry, showed an increase with time in the inhabitants
      of northern Finland. Selenium concentrations were higher in the residents of
      Lapland than in the southern Finns, but this difference occurred after the
      addition of selenium to fertilisers has begun to be less common.

PMID- 8754606
TI  - Tuberculosis and HIV infection.

PMID- 8754607
TI  - Pre-eclampsia.

PMID- 8754609
TI  - Discrepancy between patients' food ordered and received, at a teaching hospital.

PMID- 8754608
TI  - Perinatal deaths at the Castle Street Hospital for Women in 1993.
AB  - OBJECTIVE: To identify causes for perinatal mortality at the Castle Street
      Hospital for women. DESIGN: Retrospective analysis of clinical notes. SETTING:
      Castle Street Hospital for Women, Lady Ridgeway Hospital and Sri Jayawardanepura
      General Hospital. PATIENTS: All stillbirths and early neonatal deaths at the
      Castle Street Hospital for Women in 1993. RESULTS: There were 192 antepartum, 31
      intra-partum and 120 early neonatal deaths. 264 deaths were in low birth weight
      babies. Pregnancy induced hypertension, cord round the neck, anencephaly,
      antepartum haemorrhage and idiopathic respiratory distress syndrome were the
      common causes of mortality. CONCLUSION: Most deaths may have been prevented with
      better obstetric and neonatal care.

PMID- 8754610
TI  - The pattern of tissue damage in occupational trauma.
AB  - OBJECTIVE: To study the pattern of tissue damage in occupational hand injuries.
      SETTING: Trauma and Orthopaedic Unit of the General Hospital, Colombo. PATIENTS:
      190 patients with occupational hand injuries submitted to surgery by me were
      studied prospectively. The incidence of compound and simple fractures and
      dislocations, digital amputations, tendon injuries and skin loss were studied.
      The individual bones and tendons affected, the level of digital amputations and
      the involvement of individual fingers were recorded. RESULTS: Compound fractures
      accounted for 42.1% of injuries and in 56.4% the distal phalanx was involved.
      Finger tendons were affected in 66.6%. The highest incidence of compound
      fractures (30.6%), amputations (41.1%) and skin and subcutaneous tissue loss
      (28.5%) was seen in the index finger. CONCLUSIONS: 1. Compound fractures and
      digital amputations were the main injuries. 2. Distal phalanx is more frequently
      affected in compound fractures. 3. Among the amputations loss of finger tip is
      the commonest. 4. Flexor tendons were more injured than the extensor tendons. 5.
      Index finger is the most frequently injured digit.

PMID- 8754611
TI  - Normal pressure hydrocephalus.

PMID- 8754612
TI  - An audit of fresh frozen plasma transfusion in intensive care patients.

PMID- 8754613
TI  - Linking alcohol and health: irrelevant and dangerous.

PMID- 8754614
TI  - An aggressive variant of papillary carcinoma of thyroid: the tall cell type.

PMID- 8754615
TI  - Hydrophobia prophylaxis in dog bite.

PMID- 8754616
TI  - Costs of insulin injection.

PMID- 8754617
TI  - DNA recognition and structural specificities.
AB  - How a short DNA sequence interacts in a sequence specific manner with appropriate
      protein is understood only in certain systems for which high resolution crystal
      structures of the protein-DNA complexes are available. The base sequence of DNA
      is sensed directly (read-out) by the protein through the major or minor groove,
      while DNA shape also is sensed through multiple interactions with the sugar
      phosphate backbone. Several repressors, activators and restriction endonucleases
      complexed with their cognate DNA oligomers are now known and reviewed here. If
      the binding site on DNA has two fold symmetry, the protein interacts as dimer and
      uses a variety of structural motifs for specific interaction. The level of
      specificity of interaction is enhanced by flexibility and/or distortion in either
      the DNA or protein tertiary structure.

PMID- 8754618
TI  - Telomere (telomerase) hypothesis of aging and immortalization.

PMID- 8754619
TI  - RNA polymerase II dependent genes that do not code for protein.
AB  - In recent years more and more examples of RNA polymerase II dependent non-coding
      transcripts have been described. Although these have frequently been ignored as
      "selfish DNA elements", it is becoming increasingly clear that many, if not all,
      of them have very important biological roles. Examples of such "genes" from
      Drosophila, mammals, other vertebrates, yeast etc. are considered. Although the
      specific mechanisms through which these non-coding transcripts function in the
      cell are not clear, comparisons reveal certain common themes, particularly the
      importance of secondary structures, rather than the primary base sequence of
      these transcripts. While some of these transcripts may function as ribozymes or
      as anti-sense regulators, most others may function more directly through their
      specific protein-binding properties. Since RNA is believed to be the first
      "living" molecule, it is very likely that some genes even today function only
      through this class of molecules. It is expected that instead of being ignored as
      examples of "selfish DNA", a more positive search for their functions will help
      unravel the significance of this novel class of genes.

PMID- 8754620
TI  - Epididymal sperm maturation proteins.
AB  - Mammalian spermatozoa are not motile when they leave the testis. They have to
      undergo a complex maturation process to be able to fertilize in vivo. The
      maturation changes of mammalian sperm membrane have been extensively studied
      using lectins and antibodies. Some of these antigens have been purified and
      cloned. The interaction of secreted proteins with sperm membranes and acquisition
      of sperm motility as essential steps for spermatozoa to be fertile are well
      documented. The role of these epididymal maturation proteins in infertility and
      the possibility of using these antigens for immunocontraception are discussed in
      this review.

PMID- 8754621
TI  - Establishment of the functional importance of thiamin carrier protein in pregnant
      rats by using monoclonal antibodies.
AB  - Monoclonal antibodies (mAbs) to chicken thiamin carrier protein (TCP) have been
      produced by hybridoma technology to identify the crucial epitopes involved in
      bioneutralization of the vitamin carrier. The monoclonality of these mAbs (A4C4,
      F3H6, H8H3, C8C1 and G7H10) was sought to be confirmed by sub-class isotyping;
      they all belong to IgG1, k type. The epitopes recognized by all the five mAbs are
      conserved in TCP from the chicken to the rat as assessed by liquid phase RIA and
      immunoprecipitation of 125I-labelled proteins from pregnant rat serum. Among
      these mAbs. passive immunization of pregnant rats with the mAb C8C1 only on three
      consecutive days (day 10, 11 and 12) resulted in embryonic resorption. These
      results demonstrate the importance of epitopic structure specified by the mAb
      C8C1 on TCP during pregnancy in rats.

PMID- 8754622
TI  - Differential activity of protein kinase C in alveolar and peritoneal macrophages.
AB  - The characteristics of protein kinase C activity present in guinea pig alveolar
      and peritoneal macrophages have been compared and examined. The activity is
      predominantly cytosolic with preference for phosphatidyl serine as cofactor over
      other phospholipids. K(m) of protein kinase C for ATP is 30.30 and 54.05 microM
      in alveolar and peritoneal macrophages respectively. Scatchard plot analysis
      shows heterogenous binding sites for [3H]PDBu in alveolar macrophages in contrast
      to peritoneal macrophages showing homogeneous type of binding sites. PMA
      activates protein kinase C in a dose-dependent manner and shows downregulation at
      higher concentration in both alveolar and peritoneal macrophages. Endogenous
      proteins of molecular masses 77, 47, 37 and 16.5 kDa in alveolar macrophages and
      77, 47, 38 and 15.5 kDa in pertioneal macrophages are phosphorylated by PKC.
      These findings suggest that alveolar and peritoneal macrophages possess two
      different types of protein kinase C activities but phosphorylate similar proteins
      and exhibit functional similarities in these cells.

PMID- 8754623
TI  - In vivo NMR spectroscopic studies on the bioenergetic changes induced by
      metabolic modulators in Ehrlich ascites tumour cells.
AB  - Changes in the energy metabolism of Ehrlich ascites tumour (EAT) cells induced by
      treatment with 2-deoxy-D-glucose (2-DG) alone and in combination with other
      metabolic modulators, were studied using in vivo nuclear magnetic resonance (NMR)
      spectroscopy. Accumulation of 2-DG-6-phosphate (2-DG-6-P) and cellular energy
      status as reflected in the ratio of beta ATP to inorganic phosphate (beta-ATP/Pi)
      in cells could be monitored as a function of time using P-31 NMR spectroscopy.
      Presence of 2-DG induced a significant decrease in the levels of nucleotide
      triphosphates, which continued to reduce for some time even after removing 2-DG
      from the vicinity of cells. When administered along with 3-O-methyl-D-glucose (3
      O-MG), 2-DG phosphorylated at a slower rate and the resultant 2-DG-6-P
      accumulated to a lesser extent than that obtained with 2-DG alone. Treatment with
      Photosan II, a haematoporphyrin derivative (Hpd), has been reported to increase
      the glucose utilisation and rate of glycolysis. Upon concomitant administration
      of 2-DG along with Hpd (after Hpd pretreatment for 1-2 hr), the extent of
      phosphorylation of 2-DG increased. The combination of 2-DG with 3-O-MG or Hpd
      reduced the energy status (beta-ATP/Pi) to a greater extent and the recovery was
      considerably less upon removal of the treatment, compared to the effects of
      either drug administered separately. Since metabolic depletion of ATP is known to
      inhibit the post-irradiation DNA repair processes, it is hypothesized that the
      use of these drug combinations, as adjuvants to tumour radiotherapy, should
      enhance the therapeutic efficacy and selectivity.

PMID- 8754624
TI  - Thermodynamics of water-lipid interaction in presence and absence of salts.
AB  - Extents of hydration of different lipids such as cholesterol, lecithin,
      lysolecithin, gangliosides, hydroxy cerebrosides, sphingomyelin, Dalda
      (hydrogenated fat), coconut oil and sunflower oil in the presence and absence of
      some inorganic electrolytes, sucrose and urea have been studied using the
      isopiestic vapour pressure technique. Except triglycerides, the shape of the
      water vapour adsorption isotherms for other lipids are in agreement with type II
      or type III BET isotherms respectively. The overall shape of each curve for
      triglycerides does not agree with any of the shapes of five types of BET
      isotherms. At water activity (1) approaching unity, maximum number of moles of
      water bound (delta n1zero) per mole of cholesterol are 1.6 and 2.6 at 28 degrees
      C and 37 degrees C, respectively. Values of delta n1zero at 23 degrees C stand in
      the following order: Ganglioside > lysolecithin > sphingomyelin > hydroxy
      cerebrosides. For triglycerides n1 increases with increase of a1 and reaches
      maximum in between 0.95 to 0.98 beyond which it sharply decreases to zero as a1
      approaches unity. Standard free energy changes (delta Gzero) and enthalpy changes
      (delta Hzero) for cholesterol and lysolecithin have been evaluated from the
      experimental data. The excess hydration of cholesterol in the presence of several
      inorganic salts, urea and sucrose have been estimated from isopiestic experiments
      and free energies of excess hydration have been evaluated.

PMID- 8754625
TI  - Effect of cotrimoxazole (Bactrim) on cholesterol metabolism.
AB  - Male albino rats when treated with antimicrobial cotrimoxazole
      (trimethoprim+sulphamethaoxazole) showed an elevation of plasma high density
      lipoprotein (HDL) cholesterol and lecithin cholesterol acyl transferase activity
      (LCAT). Very low density lipoprotein and low density lipoprotein (VLDL+S4, 5LDL)
      cholesterol levels were decreased. However, total blood cholesterol and aortic
      cholesterol levels were normal. There was decreased synthesis of cholesterol and
      its content in the liver. Intestinal cholesterol mobilisation (studied using [U
      14C]glucose) towards lymph was normal in spite of decreased synthesis by
      intestines. Decreased fecal excretion of bile acids and neutral sterols and
      normal intestinal contribution may be mainly involved in the blood cholesterol
      homeostasis.

PMID- 8754626
TI  - Degradation of 3-hydroxybenzoic acid by a Bacillus species.
AB  - A Bacillus sp. isolated by 4-hydroxybenzoate enrichment culture technique is
      capable of utilizing 3-hydroxybenzoate as the sole source of carbon and energy.
      The organism degraded 3-hydroxybenzoic acid through the intermediate formation of
      protocatechuic acid. 3-Hydroxybenzoate 4-hydroxylase, protocatechuate 3,4
      dioxygenase and protocatechuate 4,5-dioxygenase activities were shown in cell
      free extracts. The formed protocatechuate is metabolized through both the ortho
      and meta cleavage pathway.

PMID- 8754627
TI  - Effect of protein supplemented cassava diet in rats.
AB  - The effect of feeding rats with cassava diet (tapioca) has been investigated with
      respect to the activities of superoxide dismutase, catalase and levels of TBARS.
      By varying the levels of protein in the diet and cyanide content of cassava, the
      possible role of a high protein diet in the prevention of oxidant stress has been
      shown. Rhodanese which detoxifes cyanide is also found to be inhibited in rats
      fed low protein diet while the inhibition was only marginal in the high protein
      fed groups.

PMID- 8754628
TI  - GENOLYTE: a PC-based computer program for visualisation of genomic DNA sequences.
AB  - This paper describes the program "GENOLYTE" which has been developed for the
      visualisation and identification of the global and local patterns of long genomic
      DNA sequences quickly in a few minutes, with the aid of a microcomputer. Apart
      from global and local identification, GENOLYTE comparatively depicts the
      similarity of two or more than two genomic DNA sequences. The utility of the
      program has been demonstrated by analysing the complete mitochondrial DNA
      sequences (taken from EMBL databank) as an example and the results are discussed
      from therein. The program written in TURBO C++ has the following minimum
      requirements: (i) PC 386 AT, (ii) SVGA colour monitor, (iii) the [BGI] directory
      of TURBO C++ version 3.0.

PMID- 8754629
TI  - Dielectric properties of albumin and yolk of avian egg.
AB  - The dielectric properties of albumin and yolk of eggs of hen and duck have been
      investigated using the time domain reflectometry (TDR) technique in the frequency
      range 10 MHz to 10 GHz at room temperature. The conductivity and pH values were
      also measured. It has been found that the values of dielectric constant (epsilon
      s) is lower, while the values of relaxation time tau(ps) are higher than that of
      pure water possibly due to the bound water present in the yolk and albumin of the
      avian egg. The dielectric constant for albumin is more than that for yolk of
      eggs, while reverse is found with the values of relaxation time. Also albumin
      shows approximately three times higher conductivity than that of yolk. In the
      case of relatively older (by 2 days) eggs, the dielectric parameters tend to be
      slightly increased.

PMID- 8754630
TI  - [The gene for Friedreich's ataxia: a landmark for neurology and for human
      genetics].

PMID- 8754631
TI  - The Mini Cognitive Examination for screening in epidemiologic studies of
      dementia.
AB  - We assessed the efficiency of the Mini Cognitive Examination (MCE) for detecting
      dementia and studied the influence of certain variables (age, sex, education) on
      its global rating. The study was carried out on a rural population in two stages:
      the MCE was administered in the first stage, whilst the Cambridge Mental
      Disorders of the Elderly (CAMDEX) was given in the second. The sensitivity of the
      MCE was 93.5% and specificity was 82%. Multivariate statistical analysis showed
      that the age, sex and education all had significant impacts on the MCE global
      rating. Out of 13 MCE items, only nine (temporal orientation, spatial
      orientation, calculation, repetition of a sentence, inverting the order of 3
      numbers, sequence of praxic orders, abstraction and naming of objects)
      discriminated between subjects with dementia and controls. The MCE proved to be a
      highly efficient screening instrument for dementia.

PMID- 8754632
TI  - Multiple sclerosis in Mexico: hospital cases at the National Institute of
      Neurology and Neurosurgery, Mexico City.
AB  - The frequency and clinical features of multiple sclerosis (MS) at the National
      Institute of Neurology and Neurosurgery in Mexico City for the period spanning
      1984-1993 is presented. Hospital records of patients with clinically diagnosed MS
      were selected, the frequency and cumulative frequency of this diagnosis were
      determined and demographic information and clinical features were recorded. It
      was found that 70% of the patients were women, 25% were professionals, and 95%
      were of mixed race. The clinical features of our patients and their neuroimages
      were consistent with those of MS patients in other populations. Importantly, we
      found that the frequency of MS has almost doubled over the last 10 years. The
      reason for this phenomenon is discussed as resulting from better health
      screening, the availability of nuclear magnetic resonance imaging, and the
      cultural, demographic and dietary changes that have occurred due to the rapid
      urbanization of our country.

PMID- 8754634
TI  - [Treatment of micturition disorders in multiple sclerosis].

PMID- 8754633
TI  - [Prognostic factors in amyotrophic lateral sclerosis].
AB  - Survival in patients with amyotrophic lateral sclerosis is highly variable. In a
      prospective study of 71 patients, we analyzed the influence of several clinical
      factors on survival: age of onset, sex, initial involvement (bulbar, upper
      extremities or lower extremities) and familial history. Mean time of evolution
      was 2.6 years, with 25% survival 5 years after onset. Patients under 45 years old
      had better survival than those over 45 (5.8 and 2.2 years, respectively, p <
      0.002). The prognosis for women was worse (2.07 and 3.6 years for women and men,
      respectively, p < 0.001), probably because age of onset was later in women (61
      versus 53 years, respectively, p < 0.006). Neither first symptom or familial
      history of the disease affected prognosis. We conclude that age at onset is a
      decisive prognostic factor that is inversely related to survival. In the design
      of clinical trials in which survival is a variable, the treatment and control
      groups should be matched for age.

PMID- 8754635
TI  - [Magnetic resonance of the brain in encephalitis due to Epstein-Barr virus].
AB  - Encephalitis due to Epstein-Barr virus (EEBV) is rare and the debate on possible
      pathogenic mechanisms has remained open in the absence of structural changes in
      brain images and discrepancies in serology and viral culture results. We describe
      an EEBV case in which magnetic resonance images in T1 and T2 potentiated
      sequences were normal, although intense meningeal captation and a destructive
      parenchymatous lesion could be observed after administration of gadolinium. These
      findings suggest direct infiltration of the central nervous system by the virus
      as well as a meningeal infiltrative type reaction, supporting the hypothesis that
      the pathogenic mechanisms involved is invasive rather than infectiously or
      immunologically mediated. The pattern of involvement seen in EEBV by magnetic
      resonance is different from that of other forms of viral encephalitis.

PMID- 8754636
TI  - [Benign intracranial hypertension: a new symptom and a new association].

PMID- 8754637
TI  - [Time thresholds for infarction in the territory of the middle cerebral artery].

PMID- 8754638
TI  - [Parry-Romberg syndrome].

PMID- 8754639
TI  - Studies on the most reactive purified antigen for immuno-diagnosis of hydatid
      disease.
AB  - Fourty hydatidosis patients and 36 patients with various parasitic diseases taken
      from Ain Shams University Hospitals and 15 normal controls as well were subjected
      to clinical examination, stool and urine examination, serological examination
      using indirect hemagglutination (IHA), counterimmunoelectrophoresis (CIEP) and
      enzyme-linked immunosorbent assay (ELISA) tests with crude and partially antigens
      for hydatidosis. Partial purification of crude hydatid fluid antigen abolished
      reactions in IHA test, reduced in ELISA or had no effect on cross reactions in
      the CIEP test. The crude antigen was more sensitive than the purified antigen in
      all tests applied. Using crude antigen, IHA (83%) was the most sensitive test
      followed by ELISA (68%) and then CIEP (60%) tests. In case of partially purified
      hydatid fluid antigen, CIEP was the most sensitive (58%) test with the purified
      peak I antigen followed by IHA test with peak III (48%) then ELISA with purified
      peak I (45%). In all serological tests applied, hepatic hydatidosis cases gave
      the highest reactions followed by cases of combined hepatic and pulmonary
      infections and then pulmonary cases alone.

PMID- 8754640
TI  - Uptake and development of Wuchereria bancrofti in Culex pipiens L. and Aedes
      caspius pallas.
AB  - Studies were conducted to compare early phenomena associated with W. bancrofti
      infection and further development in the filaria vector Culex pipiens and the
      refractory mosquito Aedes caspius. Ingestion rates evaluated immediately after
      simultaneous feeding on an infected human were 69.1% for 43 Cx. pipiens and 35.7%
      for 28 Ae. caspius. The observed number of mf ingested by either mosquito did not
      vary significantly (2.7 +/- 1.4, and 2.3 +/- 0.9, respectively) and, based on the
      size of the blood meal ingested (2.8 and 2.3 microliters respectively), a two
      fold mf concentration factor was recorded for both species. Blood ingested by Cx.
      pipiens (N = 16) and Ae. caspius (N = 10) clotted within 120 and 90 min post
      feeding respectively. The time difference observed, however, did not affect
      significantly the rates of migration into the hemocele (56 and 67% respectively).
      Comparison of initial infection rates with those obtained after the extrinsic
      incubation period of the parasite was completed, indicated that the proportion of
      infected Cx. pipiens was reduced by 3.9% and that of Ae. caspius by 30.0%.
      Furthermore, the observed infectivity ratio of 265 Cx. pipiens that had an
      infective blood meal was 0.74 and only 0.009 for 70 Ae. caspius. It is concluded
      that refractoriness of Ae. caspius to W. bancrofti is expressed through the
      feeding mechanism itself, by severely limiting the mf ingestion rate, and through
      physiological processes that inhibited the development of ingested worms.

PMID- 8754641
TI  - Effect of mebendazole and ivermectin in experimental hepatic capillariasis B:
      histopathological and ultrastructural studies.
AB  - Although, rodents are the principle hosts of C. hepatica both true and spurious
      human infections have been reported. Over half of the reported cases, resulted in
      death with hepatic capillariasis being discovered at autopsy; even in cases which
      the infection was detected at laparotomy or liver biopsy, the patient died due to
      the lack of suitable treatment. Therefore, studies on experimental C. hepatica in
      mice were carried out on the way of reaching a full program for treatment. The
      drugs used were mebendazole and ivermectin. The alterations noted in the egg
      shell by TEM suggest the effectiveness of the drugs used, the eggs appeared to be
      deformed; the outer shell was broken and distorted in several places. Many
      pillars were fragmented. The inner layer was also affected, where it showed
      destruction of its outer lamellae. Ultrastructural changes in the liver cells
      showed dysplastic changes. It may be a sequelae of mechanical injury or direct
      antigenic insult of the parasite or their toxins on the liver cells. During the
      course of the present work, it was noticed that most of the granulomata were in
      the fibrotic stage denoting acceleration in the process of healing of the lesions
      and no freshly deposited ova and hence no active cellular granuloma.

PMID- 8754642
TI  - Differences in susceptibility of Biomphalaria alexandrina to Schistosoma mansoni
      from Gize and Dakahlia Governorates, Egypt.
AB  - Biomphalaria alexandrina snails were collected from irrigation canals at Gize and
      Dakahlia Governorates. They were exposed to strains of Schistosoma mansoni from
      these localities. The snails showed different rates of susceptibility to the
      parasite. There was a high range of snail sensitivity to S. mansoni infection
      (53.9%-60.7%) when snail populations and parasite strains were from the same
      governorate. Supporting this was the high cercarial production from infected
      snails of these cases (288.2 cercariae/ snail/week of Dakahlia-Dakahlia group).
      However, snail populations and parasite strains from different Governorates (Gize
      Dakahlia) exhibited poor values of snail sensitivity and cercarial production
      with significant variations from those of the group of the same governorate.

PMID- 8754643
TI  - Studies on Paederus alfierii Koch (Coleoptera:Staphylinidae) with special
      reference to the medical importance.
AB  - In Egypt, the rove beetle; Paederus alfierii Koch, is an active predator of
      several insects pests attacking a wide variety of cultivated plants as maize,
      cotton, clover ... etc. On the other hand, members of genus Paederus contain
      pederin (potent toxin) which in contact with human skin causes a necrotizing
      lesion (dermatitis linearis) and with the eye causes conjunctivitis. After the
      sudden flood of the year 1994, this beetle attacked a factory and about forty
      factors suffered a form of contact dermatitis and conjunctivitis. The majority of
      such factors needed hospitalization. To fill the gap in the knowledge of medical
      importance on such a predator, the present investigation was aimed. The aqueous
      extract from twenty wild collected adults (0.0101 gm) was tested on different
      groups of albino mice. No cutaneous reaction was seen macroscopically. On the
      other hand, another group of mice (3/4) showed mild conjunctival congestion faded
      on the next day. However, these experimental findings do not indicate the
      innocence of this rove-beetle from being harmful to man. The discussion was given
      on the light of work done abroad.

PMID- 8754644
TI  - Cercariometry in the study of Schistosoma mansoni transmission in Egypt.
AB  - The recovery of Schistosoma mansoni cercariae was studied in experimental ditches
      and natural irrigation canals using a continuous operating centrifuge and a water
      suction sampling technique. Recovery of cercariae from static water in the
      ditches where caged infected Biomphalaria alexandrina snails were placed showed
      that cercariae recovered were more with increase of infected snails and decrease
      of water volume and were most abundant in the proximity of the snails which
      produced them. Shade or heavy vegetation cover reduced the recovery of cercariae.
      Results suggest also strong seasonal differences in diurnal patterns of cercarial
      recovery. An early morning peak with large number of cercariae occurred during
      hot weather while in cooler seasons cercariae appear in fewer numbers but persist
      for most of the day. Obtained information, beside contributing to knowledge of
      cercarial behaviour, should help to optimize taking water sample and consequently
      to increase efficiency of cercariometry techniques. In the natural irrigation
      system, cercariometry was significantly more sensitive in detecting transmission
      foci than snail sampling by a dip net.

PMID- 8754645
TI  - Assessment of latex indirect agglutination test (Toxolatex Fumouze) for the
      detection of Toxoplasma specific antibodies in human sera in Turkey.
AB  - Sera from 50 patients were examined with conventional ELISA, IFA and Toxolatex
      Fumouze. Out of 50 specimens only 3 false positive cases were detected with
      Toxolatex Fumouze as compared with the results of ELISA & IFA tests. Toxolatex
      Fumouze represents a rapid, highly sensitive and specific technique for screening
      of specific antibodies against toxoplasmosis, but due to false negative results,
      sera from patients at risk of severe toxoplasmosis (fetus, HIV+, transplant,
      immunosupressed) should be tested with other serological methods such as the dye
      test, DS-ELISA and ISAGA.

PMID- 8754646
TI  - Psammomys obesus Cretzschmar, 1828 and zoonotic cutaneous leishmaniasis in Sinai
      Peninsula, Egypt.
AB  - In the Middle East, the fat sand rat Psammomys obesus is the most important
      reservoir host of zoonotic cutaneous leishmamiasis (ZCL). It is the most
      incriminated host in outbreaks. Two P. obesus caught in Wadi El Gedeiret (Al
      Arish, North Sinai) were found naturally infected with Leishmania major as
      indicated by enzyme electrophoresis. In Egypt, the already known reservoir hosts
      are Gerbillus pyramidum I. Geoffroy St. Hilaire, 1825; Meriones crassus
      Sundevall, 1984 and Meriones sacramenti Thomas, 1922. The hostal role of P.
      obesus was discussed.

PMID- 8754647
TI  - Effect of X-ray on the snails of schistosomiasis in Egypt.
AB  - Biomphalaria alexandrina and Bulinus truncatus snails were exposed to sublethal
      doses 0.2, 3, 5, 10 and 20 rad of X-ray. The survival and reproductive rates of
      these snails were highly affected by these doses. The maximum survival periods of
      laboratory populations of Biomphalaria snails were less than those of field ones
      which means a high sensitivity of laboratory snails to X-ray. The reproductive
      capacity of irradiated Biomphalaria and Bulinus snails was highly suppressed and
      this will interrupt Schistosomiasis transmission. A deleterious effect of
      gametogenesis of irradiated Biomphalaria was histologically proved. After 3 weeks
      of snail irradiation with high dose (40 rad) the hermaphrodite gland became
      completely evacuated.

PMID- 8754648
TI  - Serological diagnosis of extraintestinal Sarcocystosis.
AB  - The present study was carried out on eighty patients attending Zagazig University
      Hospitals. Forty cases suffered idiopathic cardiac diseases (28 with
      cardiomyopathy, 8 with myocarditis & 4 with valvular lesions) and forty cases
      suffered idiopathic rheumatic diseases (30 with musculoskeletal complaints and 10
      with myositis). Sera were investigated by enzyme-linked immunosorbent assay
      (ELISA) and indirect fluorescent antibody technique (IFAT) using Sarcocystis
      fusiformis antigen in order to detect the role of Sarcocystis in initiation of
      these diseases. Twenty positive toxoplasmic sera and sera from twenty normal
      individuals were considered as control group. The sera of the investigated cases
      were tested against Toxoplasma gondii antigen to exclude it as one of the
      causative agents of these idiopathic lesions. No statistical difference was found
      between IFAT and ELISA in diagnosis of sarcocystosis (P < 0.05). Also, there was
      no cross reaction between Sarcocystis and Toxoplasma. This study showed that
      Sarcocystis can be considered as one of the possible causes of some idiopathic
      diseases.

PMID- 8754649
TI  - Studies on the sacculant portion of the kidney of Biomphalaria glabrata Say
      (1818) as a haemopoietic organ.
AB  - The term immunity signifies all those properties of the host which confer
      resistance to a specific infectious agent. This resistance may be of all degrees
      ranging from complete to incomplete susceptibility. The defensive functions is
      performed by various cellular and humoral components which interact with each
      other producing a co-ordinated immune response directed towards eliminating the
      pathogen or minimizing its danger. Snails as other members of the Animal Kingdom
      have their own immune system. The present study concentrated on the sacculant
      portion of the kidney of B. glabrata as a haemopoietic stem cell. The
      histological picture of this portion in the kidney as well as in-vitro culture
      was studied. (I) The histological studies showed that (a) the sacculant portion
      constituted the last fifth of the kidney highly folded with primitive epithelial
      tissue, (b) amoebocytes (10.7 +/- 0.98m) rounded, oval or amoeboid, showing
      flattening and spreading when encapsulated around foreign particles, when doing
      so, both the cytoplasm and nucleus were more basophilic, (c) the haemocytes in
      the sacculant portion were distributed either as clustering forming amoebocytic
      plugs or dense aggregation or being normal in distribution (d) there was a
      significant correlation between haemocytic diameter and shell weight and between
      shell weight and shell diameter but no significant correlation between haemocytic
      diameter and shell diameter. (II) The in-vitro studies showed that (a) The medium
      199 and fetal calf serum (3:1) produced higher number of granulocytes, (b) the
      cells differed in shape and size from those shown in histological studies of the
      kidney itself (c) the majority of the cells were large sized granulocytes and
      very few small sized hyalinocytes, (d) granulation of cytoplasm took place in the
      culture medium used more than in the sacculant portion, (e) only the smaller
      granulocytes showed greater ability for mitotic division. The results were
      photographed and discussed.

PMID- 8754650
TI  - Isolation and curing of plasmid DNA from Bacillus thuringiensis israelensis
      strains showing variable insecticidal activities.
AB  - Bacillus thuringiensis israelensis 4Q1-WT (B.t.i.) have 9 plasmids. Fourteen
      mutates of this wild type were prepared with cured plasmids. The wild bacterial
      strain the mutants and fourteen industrial strains were compared according to the
      number, size of plasmids and their potential to induce mortality to Aedes caspius
      larvae. The 108 Kb plasmid is essential for B.t israelensis to induce insect
      kill.

PMID- 8754651
TI  - Vimentin expression in different types of breast carcinoma immunohistochemical
      study.
AB  - Vimentin was preferentially expressed in medullary and high grade ductal not
      otherwise specified (NOS) carcinomas. It was not expressed in lobular carcinoma
      whether of the classical or the variant types. In the present study, 58 cases of
      invasive breast carcinomas were tested for vimentin on formaldehyde fixed
      paraffin embedded sections. Vimentin was expressed in 14/ 44 (32%) of
      infiltrating duct carcinoma NOS. It was expressed in less than 10% of tumour
      cells in 5/44 (11.4%) and in > or = 10% of tumour cells in 4/7 (57%). However,
      none of the lobular carcinoma expressed vimentin. Vimentin was expressed in 9 of
      18 (50%) of grade III infiltrating duct NOS carcinoma versus 5 of 21 (24%) of
      grade II and 0 of 5 (0%) of grade I carcinoma. It was preferentially expressed in
      tumour growing in broad anastomosing bands or sheets with numerous mitoses, high
      nuclear grade, scanty supportive stroma and extensive necrosis.

PMID- 8754653
TI  - Morphological keys for the separation of the Rhipicephalus sanguineus group of
      ticks (Acarina:Ixodidae) in Egypt.
AB  - Rhipicephalus sanguineus sensu stricto is the taxonomic baseline for the R.
      sanguineus group of ticks which consists of four species in Egypt. Because of the
      potential confusion in the differentiation of species within the group,
      particularly in the Middle East, there is an urgent need for the development of
      new diagnostic keys. Keys, based on morphological characters, are provided herein
      for the various stages of R. sanguineus ticks in Egypt. An additional plan
      provides a useful tool for distinguishing most field collected specimens.

PMID- 8754652
TI  - Observations on possible immunity to reinfection among school children after
      schistosomiasis treatment.
AB  - A total of 72 bilharzial mansonian school children aged 6-12 years were studied
      before and six months after praziquantel (PZQ) treatment. After treatment, 21
      cases showed reinfection while 51 were resistant. Using ELISA specific antibody
      assays titre levels of IgM, IgG, IgA & IgE for soluble egg antigen (SEA) and
      soluble worm antigen (SWAP), were higher among resistant cases than among
      reinfected ones before and after treatment. The levels of specific IgA & IgE
      among resistant cases were significantly higher than among reinfected cases after
      treatment. This may indicate the integrity of immune system and prominant humoral
      immune response.

PMID- 8754654
TI  - Toxic effect of ethanolic extract of Nerium oleander (Apocynaceae) leaves against
      different developmental stages of Muscina stabulans (Diptera-Muscidae).
AB  - Nerium oleander (Apocynaceae) is evergreen shrubs widely used for ornamental
      purpose in mediterranean region. The present investigation, revealed for the
      first time the insecticidal effect of ethanolic extract from leaves of this plant
      against 2nd instar larvae of the medically important false stable fly Muscina
      stabulans (Diptera: Muscidae). LC50 of the extract was 113.66 ppm. This dose
      delayed larval and pupal duration suppressed oviposition and decreased adult
      longevity of the survivors. Morphogenic abnormalities were recorded and
      photographed in larval, pupal and adult stages, which were produced from treating
      2nd instar larvae with different concentrations of the extract.

PMID- 8754655
TI  - Evaluation of IHA test for fascioliasis in cases of hepatitis C virus infection.
AB  - Human sera were collected from proven cases of fascioliasis, virus C hepatitis,
      combined fascioliasis and virus C hepatitis and from normal persons. Antibodies
      against hepatitis C virus were found to cross react in the indirect
      haemagglutination test for antibodies against Fasciola. This cross reaction
      occurred in 2 cases out of 25 cases at titres of 1/320 and 1/640. However, the
      test showed 100% sensitivity. So, this study could suggest the use of IHA test
      for human fascioliasis for screening only. This is to be aided by more specific
      serological test and by other means of investigations like sonography.

PMID- 8754656
TI  - Giardia lamblia and chronic gastritis.
AB  - One hundred and two patients suffering from giardiasis and/or chronic gastritis
      were subjected for upper gastrointestinal endoscopy. Purified immune rabbit's
      serum against Giardia lamblia was used in ELISA and immunoperoxidase (IIP)
      techniques for detection of Giardia antigen in the stomach. Results showed that
      out of 70 cases with intestinal giardiasis, 8 (11.4%) by ELISA and 6 (8.6%) by
      IIP showed gastric giardiasis. Higher percentage of gastric giardiasis (14%) was
      encountered in cases with both giardiasis and chronic gastritis (50) than in
      cases with giardiasis alone (5%) but with statistically insignificant difference
      (P > 0.05). None of the cases with chronic gastritis alone (without giardiasis)
      was positive for gastric giardiasis. Dyspepsia was the main presenting symptom in
      cases with gastric giardiasis (P < 0.05) with significant (P < 0.05) association.
      Helicobacter pylori was encountered in 6 out of 8 cases (75%) with gastric
      giardiasis (P < 0.05) with significant (P < 0.05) association. Duodenogastric
      reflux was detected in 4 out of 8 cases (50%). Histopathological changes in
      antral mucosa were detected in all cases of gastric giardiasis. This study
      indicates that under abnormal circumstances most probably with decreased gastric
      acidity, gastric giardiasis can occur in concomitance with intestinal giardiasis.
      So, one has to search for Giardia in gastric biopsies, particularly those showing
      chronic atrophic gastritis and H. pylori. Also, one has to be aware of gastric
      giardiasis as a possible cause of upper gastrointestinal symptoms.

PMID- 8754657
TI  - Effect of some parasitic infection on neurotransmitters in the brain of
      experimentally infected mice before and after treatment.
AB  - The effects of some parasitic infection (bilharziasis, toxocariasis and
      trichinosis) on the brain of experimentally infected mice were investigated.
      Eighty animals were classified into four groups, group I contained five non
      infected animals as a control group. The other groups each contained twenty-five
      mice infected with Schistosoma mansoni (group II), Toxocara canis (group III) and
      Trichinella spiralis (group IV). Each infected group was divided into two
      subgroups (a,b). Subgroup (a) left untreated and subgroups (b) treated by
      praziquantel (in group II) and mebendazole (in group III and IV).
      Histopathological and immunological examination using peroxidase antiperoxidase
      (PAP) technique and neurotransmitters estimation (nor-epinephrine, dopamine and
      serotonine) were carried. In the untreated animals, there were mild
      histopathological changes and mild antigenic deposition in subgroups (IIa and
      IIIa) and marked changes in subgroup (IVa). There were significant decrease in
      dopamine in subgroup (IIIa), not improved after treatment (subgroup IIIb) and
      significant decrease in nor-epinephrine and serotonine in subgroup (IVa) improved
      after treatment in subgroup (IVb). The neurotransmitters changes may explain the
      motor, behavioural and emotional changes that occurred with these parasites.

PMID- 8754658
TI  - Parasitic infections presenting as prolonged fevers.
AB  - Over two successive years, out of 187 cases of fevers of undetermined origin
      (FUO) admitted to Abbassia and Embaba Fever Hospitals, 30 (16%) cases proved to
      be of parasitic origin. Ten within normal subjects were taken as controls.
      Complete blood picture, repeated stool examination, rectal snip by transparency
      technique, ELISA for specific IgM antibodies for S. mansoni, indirect
      haemagglutination test for S. mansoni, Fasciola, hydatid, amoebic liver abscess
      and toxoplasmosis, indirect fluorescent antibody test for toxoplasmosis and
      abdominal ultrasonography were performed whenever indicated. Cases comprised 8
      (26%) acute S. mansoni, 7 (24%) acute fascioliasis, 3 (10%) hydatid cyst, 8 (26%)
      amoebic liver abscess, 2 (7%) toxoplasmoisis and 2 (7%) malaria cases. The
      clinical picture of acute S. mansoni and acute fascioliasis were similar in the
      form of prolonged fever, diarrhea, hepatomegaly and leucocytosis with high
      eosinophilia. Serology (ELISA and IHAT) was essential in differentiating them.
      Abdominal ultrasonography is an easy, sensitive, cheap, non-invasive technique
      aiding in the diagnosis of amoebic liver abscess, liver hydatid cysts and
      fascioliasis but again serology was essential in differenting them. Toxoplasmic
      lymphadenitis mimic the clinical picture of infectious mononucleosis. Serology
      (monospot test, IHAT, IFAT) clinched the diagnosis. Malaria cases presented
      atypically by gastrointestinal manifestations and hepatic affection. Diagnosis
      was by positive blood smears.

PMID- 8754659
TI  - Effect of anti-schistosomal treatment on schistosomal hepatic pathology: an
      experimental study in Syrian golden hamsters.
AB  - Thirty Syrian golden hamsters were infected with Schistosoma mansoni and 10 were
      used as negative controls. Hamsters were infected by 100 cercariae; 15 were
      treated by praziquantel in doses of 100 mg/kg at 12, 13, 14 and 15 weeks
      postinfection, and 15 hamsters were left as positive control. Five from each
      subgroup were sacrificed at 24, 28 and 32 weeks after infection. Animals were
      subjected to weekly analysis for total plasma protein, serum albumin and urinary
      total protein excretion. At the end point, animals were sacrificed and the
      mesenteric venous plexus was explored for adult worms. Liver and splenic
      specimens were examined by light microscopy, and immunofluorescence microscopy.
      Complete parasite eradication was achieved in the treated animals. Although,
      there were significantly higher plasma total protein and albumin in the treated
      group, there was no significant differences in proteinuria. Histopathological
      examination of liver specimens showed highly significant reduction of granulomas,
      CAA and CCA, while amyeloid deposition showed minimal reduction in treated
      animals. Histopathological examination of splenic specimens showed highly
      significant reduction of fibrosis, granulomas, CAA and CCA, while follicular
      hyperplasia and amyeloid deposition showed non significant reduction.

PMID- 8754660
TI  - Assignment of the crystal toxin genes of the mosquitocidal bacterium, Bacillus
      thuringiensis israelensis to a specific plasmid.
AB  - Bacillus thuringiensis israelensis 4Q1-WT and the prepared mutants, 4Q1-72 and
      4Q1-81 were bioassayed against Aedes caspius larvae. The strain -4Q1-WT, which
      contains all plasmid arrys and the strain 4Q1-72 which contains the 108 kb
      plasmid gave 100% mortality, while stain 4Q1-81 which contains no plasmids gave
      0% mortality. Crystals from all tested strains were isolated, solubilized and
      characterized using PAGE to detect any homology or difference in crystal
      production, properties, and the relatedness to the plasmid profile.

PMID- 8754661
TI  - An unusually severe bee-sting allergic reaction in a bee keeper boy.
AB  - Honey bee sting allergy is not a new problem, nor is venom immunotherapy a new
      solution. Advances in scientific and immunologic theory and technology have been
      solved many problem. This paper report an unusually severe bee sting allergy in a
      son of a bee keeper.

PMID- 8754662
TI  - [Focus groups: preliminary experiences in educational health programs in Brazil].
AB  - Since 1989, the public health education section of the University of Sao Paulo
      (USP), Brazil, has been using the focus group technique to identify educational
      problems and evaluate programs being developed. The focus group is a research
      technique that allows qualitative data to be collected through group sessions
      involving 6 to 15 persons with some shared trait (for example, sex, age,
      occupation, role in the community). The group discusses various aspects of a
      specified subject. This paper describes five research projects in which this
      technique was used. The projects were carried out by professors in the School of
      Public Health/USP in the state of Sao Paulo between 1989 and 1992 with population
      groups and in health institutions. These experiences showed that the technique is
      efficient, permitting rapid identification and in-depth analysis of problems from
      the point of view of the population. Among the drawbacks to the technique is that
      it uses a small and nonrandom sample, which means that in certain cases focus
      groups should be considered a complement to quantitative studies. The data
      described here provide knowledge of perceptions, ideas, opinions, expectations,
      and social images-in short, the cultural and verbal universe of the population.
      With this information, educators and administrators can plan and evaluate
      education programs on the basis of the needs and views of the people they serve,
      putting into practice the plan to make education more democratic and responsive
      to the needs of its public.

PMID- 8754663
TI  - [Organochlorine pesticide residues in cow's milk, Nicaragua].
AB  - This work reports on a preliminary study carried out in Nicaragua to build a
      profile of the contamination of cow's milk with 10 organochlorine pesticides and
      make recommendations based on the findings. Between December 1993 and March 1994,
      milk samples were collected from 48 different sites in the country. The samples
      were analyzed for residues of hexachlorobenzene (HCB), alpha-BHC, lindane,
      aldrin, dieldrin, oxychlordane, heptachlor epoxide, and the principal metabolites
      of DDT (p,p'-TDE, p,p'-DDE, and p,p'-DDT) by means of solid-phase extraction from
      milk fat, and the quantity of the residues was determined by gas chromatography
      with electron capture detection. Heptachlor epoxide was found in 1 milk sample,
      dieldrin in 1, lindane in 3, oxychlordane in 3, alpha-BHC in 3, aldrin in 6, HCB
      in 9, and metabolites of DDT in 39 (81% of the samples). The six samples most
      heavily contaminated with by-products of DDT came from the departments of Leon
      and Chinandega, in the Pacific region, where there used to be intensive cotton
      production. The highest concentration was found in the sample from Malpaisillo,
      with 1105 micrograms of pesticide per kg of milk fat. The authors recommend that
      studies should be done so that the risk of contamination of other food products
      can be estimated, and that the public's health should be protected through strict
      control of the production or importation, storage, sale, and use of
      organochlorine pesticides.

PMID- 8754664
TI  - [Mortality among drug users with and without HIV].

PMID- 8754665
TI  - [Epidemiology of vitamin A deficiency in northeastern Brazil].

PMID- 8754666
TI  - [Regional Plan for Investments in Environment and Health for Latin America and
      the Caribbean].

PMID- 8754667
TI  - Women's health care issues for medical students: an education proposal.
AB  - This outline of objectives in women's health care education is intended to
      provide a model for reviewing medical school curricula by interdisciplinary
      educators on a national basis to identify core knowledge, skill, and attitudes
      for medical student education. Review of the core objectives identified for
      internal medicine, pediatrics, family medicine, and surgery allows us to identify
      those that are essential to good patient care so they can be reinforced and
      evaluated at various outcome points. Developing learning objectives that are
      complementary rather than additive, that clarify important objectives for
      students, that bring course directors into collaborative communication, and that
      ultimately improve communication will require an atmosphere of cooperation among
      disciplines.

PMID- 8754668
TI  - Review of APGO women's health curricula proposal.

PMID- 8754669
TI  - Primary prevention of osteoporosis: pediatric approach to disease of the elderly.

PMID- 8754670
TI  - Prevalence of domestic violence among women seeking abortion services.

PMID- 8754671
TI  - Delivering breast and cervical cancer screening services to underserved women:
      Part II. Implications for policy.
AB  - Many breast and cervical cancer screening (BCCS) programs for underserved women
      employ strategies to increase the use of preventive services. In Phase I of a two
      phase study, strategies were identified and assessed. In Phase II, we further
      assess strategies previously identified and comment on policy implications. Site
      visits were conducted at BCCS programs that had used one successful strategy
      identified during Phase I, provided services to underserved women, and were
      located in different geographic regions. The federally funded National Breast and
      Cervical Cancer Early Detection Programs (NBCCEDP) were also considered for site
      visits. Interviews were completed and available data were reviewed. A descriptive
      and qualitative analysis was completed. Programs visited were found to be
      increasing the use of BCCS services for the defined target populations. Some
      programs focused on outreach and recruitment. Other programs focused on clinical
      preventive services with little emphasis on outreach and recruitment. Management
      information systems were used by most programs. We found that there continues to
      be a large number of women not receiving BCCS services. Some programs have had to
      limit outreach and recruitment because the clinical preventive services offered
      are at capacity. Programs need to have a balanced approach to providing services
      from the outset. Existing programs may need to establish partnerships to provide
      comprehensive BCCS services to underserved women. Because the unmet need (women
      who have not received BCCS services) exceeds available clinical preventive
      services, it is a challenge to know how to best use available resources.

PMID- 8754672
TI  - The relationship between college females' drinking and their sexual behaviors.

PMID- 8754673
TI  - Obstetric fistulas in Africa and the developing world: new efforts to solve an
      age-old problem.

PMID- 8754674
TI  - Prenatal care: will the past predict the future?

PMID- 8754675
TI  - Are Asian/Pacific Islander American women represented in women's health research?

PMID- 8754676
TI  - Photosystem I.

PMID- 8754677
TI  - A brassinosteroid-insensitive mutant in Arabidopsis thaliana exhibits multiple
      defects in growth and development.
AB  - Brassinosteroids are widely distributed plant compounds that modulate cell
      elongation and division, but little is known about the mechanism of action of
      these plant growth regulators. To investigate brassinosteroids as signals
      influencing plant growth and development, we identified a brassinosteroid
      insensitive mutant in Arabidopsis thaliana (L.) Henyh. ecotype Columbia. The
      mutant, termed bri1, did not respond to brassinosteroids in hypocotyl elongation
      and primary root inhibition assays, but it did retain sensitivity to auxins,
      cytokinins, ethylene, abscisic acid, and gibberellins. The bri1 mutant showed
      multiple deficiencies in developmental pathways that could not be rescued by
      brassinosteroid treatment including a severely dwarfed stature; dark green,
      thickened leaves; males sterility; reduced apical dominance; and de-etiolation of
      dark-grown seedlings. Genetic analysis suggests that the Bri1 phenotype is caused
      by a recessive mutation in a single gene with pleiotropic effects that maps 1.6
      centimorgans from the cleaved, amplified, polymorphic sequence marker DHS1 on the
      bottom of chromosome IV. The multiple and dramatic effects of mutation of the
      BRI1 locus on development suggests that the BRI1 gene may play a critical role in
      brassinosteroid perception or signal transduction.

PMID- 8754678
TI  - Uncoupled defense gene expression and antimicrobial alkaloid accumulation in
      elicited opium poppy cell cultures.
AB  - Treatment of opium poppy (Papaver somniferum L.) cell cultures with autoclaved
      mycelial homogenates of Botrytis sp. resulted in the accumulation of
      sanguinarine. Elicitor treatment also caused a rapid and transient induction in
      the activity of tyrosine/dopa decarboxylase (TYDC, EC 4.1.1.25), which catalyzes
      the conversion of L-tyrosine and L-dopa to tyramine and dopamine, respectively,
      the first steps in sanguinarine biosynthesis. TYDC genes were differentially
      expressed in response to elicitor treatment. TYDC1-like mRNA levels were induced
      rapidly but declined to near baseline levels within 5 h. In contrast, TYDC2-like
      transcript levels increased more slowly but were sustained for an extended
      period. Induction of TYDC mRNAs preceded that of phenylalanine ammonia-lyase
      (PAL, EC 4.3.1.5) mRNAs. An elicitor preparation from Pythium aphanidermatum was
      less effective in the induction of TYDC mRNA levels and alkaloid accumulation;
      however, both elicitors equally induced accumulation of PAL transcripts. In
      contrast, treatment with methyl jasmonate resulted in an induction of TYDC but
      not PAL mRNAs. The calmodulin antagonist N-(6-aminohexyl)-5-chloro-1
      naphthalenesulfonamide and the protein kinase inhibitor staurosporine partially
      blocked the fungal elicitor-induced accumulation of sanguinarine. However, only
      staurosporine and okadaic acid, an inhibitor of protein phosphatases 1 and 2A,
      blocked the induction of TYDC1-like transcript levels, but they did not block the
      induction of TYDC2-like or PAL transcript levels. These data suggest that
      activation mechanisms for PAL, TYDC, and some later sanguinarine biosynthetic
      enzymes are uncoupled.

PMID- 8754679
TI  - The arabidopsis ACT7 actin gene is expressed in rapidly developing tissues and
      responds to several external stimuli.
AB  - ACT7 encodes one of the six distinct and ancient subclasses of actin protein in
      the complex Arabidopsis actin gene family. We determined the sequence and
      structure of the Arabidopsis thaliana ACT7 actin gene and investigated its tissue
      specific expression and regulation. The ACT7 mRNA levels varied by 128-fold among
      several different tissues and organs. The highest levels of aCT7 mRNA were found
      in rapidly expanding vegetative organs, the lowest in pollen. A translational
      fusion with the 5' end of ACT 7 (1.9 kb) joined to the beta-glucuronidase
      reporter gene was strongly and preferentially expressed in all young, developing
      vegetative tissues of transgenic Arabidopsis plants. ACT7 was the only
      Arabidopsis actin gene strongly expressed in the hypocotyl and seed coat.
      Although no beta-glucuronidase expression was seen in developing ovules or
      immature seeds, strong expression was seen in dry seeds and immediately after
      imbibition in the entire seedling. ACT7 was the only Arabidopsis actin gene to
      respond strongly to auxin, other hormone treatments, light regime, and wounding,
      and may be the primary actin gene responding to external stimuli. The ACT7
      promoter sequence contains a remarkable number of motifs with sequence similarity
      to putative phytohormone response elements.

PMID- 8754680
TI  - Quantification of free plus conjugated indoleacetic acid in arabidopsis requires
      correction for the nonenzymatic conversion of indolic nitriles.
AB  - The genetic advantages to the use of Arabidopsis thaliana mutants for the study
      of auxin metabolism previously have been partially offset by the complexity of
      indolic metabolism in this plant and by the lack of proper methods. To address
      some of these problems, we developed isotopic labeling methods to determine
      amounts and examine the metabolism of indolic compounds in Arabidopsis. Isolation
      and indentification of endogenous indole-3-acetonitrile (IAN; a possible
      precursor of the auxin indole-3-acetic acid [IAA]) was carried out under mild
      conditions, thus proving its natural occurrence. We describe here the synthesis
      of 13C1-labeled IAN and its utility in the gas chromatography-mass spectrometry
      quantification of endogenous IAN levels. We also quantified the nonenzymatic
      conversion of IAN to IAA under conditions used to hydrolyze IAA conjugates. 13C1
      Labeled IAN was used to assess the contribution of IAN to measured IAA following
      hydrolysis of IAA conjugates. We studied the stability and breakdown of the
      indolic glucosinolate glucobrassicin, which is known to be present in
      Arabidopsis. This is potentially an important concern when using Arabidopsis for
      studies of indolic biochemistry, since the levels of indolic auxins and auxin
      precursors are well below the levels of the indolic glucosinolates. We found that
      under conditions of extraction and base hydrolysis, formation of IAA from
      glucobrassicin was negligible.

PMID- 8754681
TI  - The impact of alteration of polyunsaturated fatty acid levels on C6-aldehyde
      formation of Arabidopsis thaliana leaves.
AB  - C6-aldehydes are synthesized via lipoxygenase/hydroperoxide lyase action on
      polyunsaturated fatty acid (PUFA) substrates in plant leaves. The source pools
      and subcellular location of the processes are unknown. A close relationship is
      found between the composition of PUFA and the composition of C6-aldehydes. In the
      current study, this relationship was tested using the Arabidopsis PUFA mutant
      lines act1, fad2, fad3, fad5, fad6, and fad7. The results indicate that C6
      aldehyde formation is influenced by the alteration of C18 PUFA levels. Mutants
      act1 and fad5, which are deficient in C16 unsaturated fatty acids, had wild-type
      levels of C6-aldehyde production. Mutants deficient in the chloroplast
      hexadecenoic acid/oleic acid desaturase (fad6) or hexadecadienoic acid/linoleic
      acid desaturase (fad7) had altered C6-aldehyde formation in a pattern similar to
      the changes in the PUFA. Mutations that impair phosphatidylcholine desaturase
      activity, such as fad2 and fad3, however, resulted in increased E-2-hexenal
      formation. The enzymes involved in C6-aldehyde production were partially
      characterized, including measurement of pH optima. The differences in C6-aldehyde
      formation among the fatty acid mutants of Arabidopsis appeared not to result from
      alteration of lipoxygenase/hydroperoxide lyase pathway enzymes. Investigation of
      the fatty acid composition in leaf phospholipids, glycolipids, and neutral lipids
      and analysis of the fatty acid composition of chloroplast and extrachloroplast
      lipids indicate that chloroplasts and glycolipids of chloroplasts may be the
      source or major source of C6-aldehyde formation in Arabidopsis leaves.

PMID- 8754682
TI  - Pedicel breakstrength and cellulase gene expression during tomato flower
      abscission.
AB  - Six cellulase genes were isolated from total RNA of the ethylene-treated tomato
      (Lycopersicon esculentum Mill.) flower abscission zone by reverse-transcription
      polymerase chain reaction using degenerate primers to conserved amino acid
      sequences from known plant cellulases. Four of the gene fragments are homologous
      to fruit pericarp cellulases. The other two are novel cellulase genes, referred
      to as Cel5 and Cel6. Breakstrength and cellulase gene expression were then
      analyzed in naturally abscising flowers and flower explants. In both naturally
      abscising flowers and flower explants induced to abscise in air or ethylene, both
      new cellulase mRNAs were correlated with flower shedding. Whereas the Cel5 mRNA
      increased in later stages of abscission, the Cel6 mRNA was present in
      nonabscising flowers and then decreased in the final stage of abscission. A third
      cellulase, Cel1, increased during the final stage of abscission in flower
      explants and yet did not increase during shedding in planta, although it was
      detectable at low levels in all abscission stages. Cel1 and Cel5 mRNA decreased
      99% when indole-3-acetic acid was added during ethylene treatment, consistent
      with low levels of abscission (3%). In contrast, Cel6 mRNA increased slightly
      when indole-3-acetic acid was added. These results suggest that abscission is a
      multistep process involving both activated and repressed cellulase genes and that
      the relative importance of each cellulase in the process depends on the
      physiological conditions under which abscission takes place.

PMID- 8754683
TI  - Physical association of starch biosynthetic enzymes with starch granules of maize
      endosperm. Granule-associated forms of starch synthase I and starch branching
      enzyme II.
AB  - Antibodies were used to probe the degree of association of starch biosynthetic
      enzymes with starch granules isolated from maize (Zea mays) endosperm. Graded
      washings of the starch granule, followed by release of polypeptides by
      gelatinization in 2% sodium dodecyl sulfate, enables distinction between strongly
      and loosely adherent proteins. Mild aqueous washing of granules resulted in near
      complete solubilization of ADP-glucose pyrophosphorylase, indicating that little,
      if any, ADP-glucose pyrophosphorylase is granule associated. In contrast, all of
      the waxy protein plus significant levels of starch synthase I and starch
      branching enzyme II (BEII) remained granule associated. Stringent washings using
      protease and detergent demonstrated that the waxy protein, more than 85% total
      endosperm starch synthase I protein, and more than 45% of BEII protein were
      strongly associated with starch granules. Rates of polypeptide accumulation
      within starch granules remained constant during endosperm development. Soluble
      and granule-derived forms of BEII yielded identical peptide maps and overlapping
      tryptic fragments closely aligned with deduced amino acid sequences from BEII
      cDNA clones. These observations provide direct evidence that BEII exits as both
      soluble and granule-associated entities. We conclude that each of the known
      starch biosynthetic enzymes in maize endosperm exhibits a differential propensity
      to associate with, or to become irreversibly entrapped within, the starch
      granule.

PMID- 8754684
TI  - Biochemical characterization of the extracellular phosphatases produced by
      phosphorus-deprived Chlamydomonas reinhardtii.
AB  - We have examined the extracellular phosphatases produced by the terrestrial green
      alga Chlamydomonas reinhardtii in response to phosphorus deprivation. Phosphorus
      deprived cells increase extra-cellular alkaline phosphatase activity 300-fold
      relative to unstarved cells. The alkaline phosphatases are released into the
      medium by cell-wall-deficient strains and by wild-type cells after treatment with
      autolysin, indicating that they are localized to the periplasm. Anion-exchange
      chromatography and analysis by nondenaturing polyacrylamide gel electrophoresis
      revealed that there are two major inducible alkaline phosphatases. A calcium
      dependent enzyme composed of 190-kD glycoprotein subunits accounts for 85 to 95%
      of the Alkaline phosphatase activity. This phosphatase has optimal activity at pH
      9.5 and a Km of 120 to 262 microns for all physiological substrates tested, with
      the exception of phytic acid, which it cleaved with a 50-fold lower efficiency.
      An enzyme with optimal activity at pH 9 and no requirement for divalent cations
      accounts for 2 to 10% of the alkaline phosphatase activity. This phosphatase was
      only able to efficiently hydrolyze arylphosphates. The information reported here,
      in conjunction with the results of previous studies, defines the complement of
      extracellular phosphatases produced by phosphorus-deprived Chlamydomonas cells.

PMID- 8754685
TI  - A metal-accumulator mutant of Arabidopsis thaliana.
AB  - A mutation designated man1 (for manganese accumulator) was found to cause
      Arabidopsis thaliana seedlings to accumulate a range of metals. The man1 mutation
      segregated as a single recessive locus located on chromosome 3. When grown on
      soil, mutant seedlings accumulated Mn (7.5 times greater than wild type), Cu (4.6
      times greater than wild type), Zn (2.8 times greater than wild type), and Mg (1.8
      times greater than wild type) in leaves. In addition to these metals, the man1
      mutant accumulated 2.7-fold more S in leaves, primarily in the oxidized form,
      than wild-type seedlings. Analysis of seedlings grown by hydroponic culture
      showed a similar accumulation of metals in leaves of man1 mutants. Roots of man1
      mutants also accumulated metals, but unlike leaves they accumulated 10-fold more
      total Fe (symplasmic and apoplasmic combined) than wild-type roots. Roots of man1
      mutants possessed greater (from 1.8- to 20-fold) ferric-chelate reductase
      activity than wild-type seedings, and this activity was not responsive to changes
      of Mn nutrition in either genotype. Taken together, these results suggest that
      the man1 mutation disrupts the regulation of metal-ion uptake or homeostasis in
      Arabidopsis.

PMID- 8754686
TI  - A calcium and free fatty acid-modulated protein kinase as putative effector of
      the fusicoccin 14-3-3 receptor.
AB  - A protein kinase that is activated by calcium and cis-unsaturated fatty acids has
      been characterized from oat (Avena sativa L.) root plasma membranes. The kinase
      phosphorylates a synthetic peptide with a motif (-R-T-L-S-) that can be
      phosphorylated by both protein kinase C (PKC) and calcium-dependent protein
      kinase (CDPK)-type kinases. Calphostin C and chelerythrine, two PKC inhibitors,
      completely inhibited the kinase activity with values of inhibitor concentration
      for 50% inhibition of 0.7 and 30 microns, respectively. At low Ca2+
      concentrations cis-unsaturated fatty acids (linolenic acid, linoleic acid,
      arachidonic acid, and oleic acid) stimulated the kinase activity almost 10-fold.
      The two inhibitors of the kinase, calphostin C and chelerythrin, strongly reduced
      the fusicoccin (FC)-induced H+ extrusion, and the activators of the kinase, the
      cis-unsaturated fatty acids, prevented [3H]FC binding to the FC 14-3-3 receptor.
      CDPK antibodies cross-reacted with a 43-kD band in the plasma membrane and in a
      purified FC receptor fraction. A polypeptide with the same apparent molecular
      mass was recognized by a synthetic peptide that has a sequence homologous to the
      annexin-like domain from barely 14-3-3. The possibility of the involvement of a
      kinase, with properties from both CDPK and PKC, and a phospholipase A2 in the FC
      Signal transduction pathway is discussed.

PMID- 8754687
TI  - Sugar regulation of harvest-related genes in asparagus.
AB  - The signals controlling the abundance of transcripts up-regulated (pTIP27,
      pTIP31, and pTIP32) or down-regulated (pTIP20 and pTIP21) after harvest in
      asparagus (Asparagus officinalis L.) spears were examined. pTIP27 and pTIP31 are
      known to encode asparagine synthetase (AS) and a beta-galactosidase (beta-gal)
      homolog, respectively. The nucleotide sequences of pTIP20, pTIP21, and pTIP32
      were determined, and they encode histone 3, histone 2B, and an unknown product,
      respectively. Changes in respiration, soluble sugars, and abundance of the five
      mRNAs were similar in the tips stored as 30-mm lengths or as part of 180-mm
      spears. We previously hypothesized that sugars may regulate the level of AS
      transcripts in asparagus tissue. Asparagus cell cultures were used to test the
      role of sugar status may regulate the level of AS transcripts in asparagus
      tissue. Asparagus cell cultures were used to test the role of sugar status in
      regulating gene expression. Transcript abundance for AS, beta-gal, and pTIP32 was
      low in cells in sugar-containing medium but increased within 12 h after
      transferring cells to a sugar-free medium. Histone 3 and histone 2B transcripts
      were, in general, abundant in cells on sugar-containing medium but declined in
      abundance when transferred to sugar-free medium. When cells were returned to
      sugar-containing medium the abundance of transcripts for histone 3 and histone 2B
      increased, whereas that for AS, beta-gal, and pTIP32 decreased. Soluble sugar
      levels are known to decline rapidly in the tips of harvested spears. Metabolic
      regulation by sugar status may have a major influence on gene expression in
      asparagus spears and other tissue after harvest.

PMID- 8754688
TI  - Purification and characterization of chaperonin 60 and heat-shock protein 70 from
      chromoplasts of Narcissus pseudonarcissus.
AB  - In chromoplast differentiation during flower formation in Narcissus
      pseudonarcissus, the molecular chaperones chaperonin 60 (Cpn60; alpha and beta)
      and heat-shock protein 70 (Hsp70) greatly increase in abundance. Both were
      purified and shown to be present in a functional form in chromoplasts, indicating
      their requirement in the extensive structural rearrangements during the
      chloroplast-to-chromoplast transition. The purified proteins, sequenced N
      terminally and from internal peptides, showed strong homology to plastid Cpn60
      and Hsp 70 representatives from other plant species. During chromoplast
      differentiation, the carotenoid biosynthetic pathway is strongly induced. The
      corresponding enzymes are all nuclear encoded and form a large, soluble, hetero
      oligomeric protein complex after import but prior to their membrane attachment.
      By immunoprecipitations we have shown that the plastid Hsp70 is a structural
      constituent of a soluble entity also containing phytoene desaturase.

PMID- 8754689
TI  - Time is muscle.

PMID- 8754690
TI  - Crystal balls, pain, fear, and euthanasia.

PMID- 8754691
TI  - Ticket on the Titanic. Perils and pitfalls of junior faculty development.

PMID- 8754692
TI  - Astute readers help.

PMID- 8754693
TI  - Capitation method ruffles feathers.

PMID- 8754694
TI  - Capitation method ruffles feathers.

PMID- 8754696
TI  - Increasing the abilities of family doctors.

PMID- 8754697
TI  - Guidelines for CME need revamping.

PMID- 8754698
TI  - The fetus as a passive smoker.

PMID- 8754699
TI  - Dilemmas in care of the elderly.

PMID- 8754700
TI  - Delisting of drugs in Ontario. How attitudes and prescribing strategies of family
      physicians in the Kingston area changed.
AB  - OBJECTIVE: To assess how attitudes and prescribing strategies of family
      physicians changed when drugs were delisted from the Ontario Drug Benefit
      formulary. DESIGN: Mailed, self-administered survey. SETTING: Family physicians'
      offices in Ontario. PARTICIPANTS: All family physicians practising in the
      Kingston, Frontenac, Lennox, and Addington Health District. MAIN OUTCOME
      MEASURES: Physicians were presented with six vignettes involving patients
      receiving a delisted drug. The choices were to recommend the patient pay for the
      medication, to substitute a drug still listed on the formulary, to make a special
      request that the medication be covered for this patient, or to offer another
      option. As well, the physicians were asked to indicate, on a 5-point Likert
      scale, their opinions regarding the effect of delisting on themselves and their
      patients. RESULTS: Physicians were most likely to change to a medication that was
      still on the formulary. Patient sex and ability to pay were factors in
      physicians' decisions. Physicians believe that the delistings are not likely to
      have adversely affected patients' health, that noncompliance is a problem because
      many once-daily formulations have been removed, that suitable alternatives are
      not always available, and that physicians should have been consulted more before
      the changes were made. CONCLUSIONS: Physicians usually substitute listed
      medications for medications that have been delisted. This is especially true for
      female patients and patients who are unable to pay.

PMID- 8754701
TI  - How family influences practice of obstetrics. Do married women family physicians
      make different choices?
AB  - PURPOSE: To examine the influence of family, past and current, on married women
      family physicians' and to understand why and how some women continue to practise
      obstetrics. PARTICIPANTS: Purposive sample of nine married women family
      physicians who currently practise obstetrics. METHOD: Qualitative in-depth
      interviews. FINDINGS: Analysis identified four main influences of family on
      participants' practice of obstetrics: family of origin, transitions in the life
      cycle, children, and the marital relationship. CONCLUSIONS: These women described
      how they combined the roles of wife, mother, daughter, sister, and doctor. Family
      was a powerful influence throughout their practice lives. Finding a balance
      between the demands of practice, particularly obstetrics, and family
      relationships was an ongoing process. The process was also influenced by
      transitions in the life cycle.

PMID- 8754702
TI  - Acute care of myocardial infarction.
AB  - Patients with acute myocardial infarct (AMI) need rapid diagnosis and prompt
      initiation of thrombolytic therapy. Patients with suspected cardiac ischemia must
      receive a coordinated team response by the emergency room staff including rapid
      electrocardiographic analysis and a quick but thorough history and physical
      examination to diagnose AMI. Thrombolysis and adjunct therapies should be
      administered promptly when indicated. The choice of thrombolytics is predicated
      by the location of the infarct.

PMID- 8754703
TI  - Antithrombotic therapy in atrial fibrillation.
AB  - OBJECTIVE: To review the evidence for antithrombotic therapy in patients with
      nonrheumatic atrial fibrillation. QUALITY OF EVIDENCE: Five primary prevention
      trials and one secondary prevention trial compare antithrombotic therapy with
      placebo or no treatment. Two trials also determine the efficacy and safety of
      acetylsalicylic acid. MAIN FINDINGS: Warfarin reduces the risk of stroke by 68%.
      The effect is consistent in all identifiable groups of patients with nonrheumatic
      atrial fibrillation, except patients at serious risk of hemorrhage. The absolute
      benefit of anticoagulants varies among patients because of markedly different
      inherent risk of stroke among patient subgroups. CONCLUSIONS: Anticoagulant
      therapy should be considered for all patients with atrial fibrillation. Oral
      anticoagulant therapy is more effective than ASA in reducing the risk of stroke
      among patients with nonrheumatic atrial fibrillation.

PMID- 8754704
TI  - Muscle cramps and magnesium deficiency: case reports.
AB  - Magnesium deficiency is more common than is believed. This article discusses
      florid magnesium deficiency in two patients and the results of treatment. While
      neither case was difficult to diagnose, the severity of symptoms was unusual.
      Magnesium deficiency should always be included in the differential diagnosis of
      patients who present with persistent or severe muscle pain.

PMID- 8754705
TI  - Certification examination of the College of Family Physicians of Canada. Part 3:
      Short-answer management problems.

PMID- 8754706
TI  - Medical ethics during genocide.

PMID- 8754707
TI  - Field neurology: the role of the U.S. Army neurologist under MedForce 2000.

PMID- 8754708
TI  - A system for tracking patients at forward medical treatment facilities.
AB  - A computerized, prototype patient tracking system, designed for a forward medical
      treatment facility (MTF), was developed and tested. The system, named MEDTRAK,
      was tested in a side-by-side comparative evaluation with the current manual
      method of patient tracking. Results of the evaluation showed that the MEDTRAK
      system admitted, identified, and tracked patients within the MTF significantly
      more accurately than did the current manual system. Furthermore, the types of
      tracking errors produced by the manual system were found to be more detrimental
      to both the effective operation of the MTF and to the discharge of theater
      evacuation policy than were those produced by the MEDTRAK system. In addition to
      improved patient accountability, the MEDTRAK system reduced the administrative
      burden that patient tracking placed on medical personnel, thereby allowing them
      to perform clinical duties.

PMID- 8754709
TI  - African-American dentists in the U.S. Army: the origins.
AB  - The majority of the dentists mentioned in this work are unknown both to dental
      and military historians. However, the contributions of Dr. William T. Jefferson,
      the first African-American dentist to treat U.S. Army soldiers in Cuba, Dr.
      William A. Birch, the first black hospital steward/dentist to serve unofficially
      (as a dentist) overseas in the Philippine campaign, and the dental veterans of
      1917-1918, deserve recognition. They were among the early pioneers in the U.S.
      Army's dental history.

PMID- 8754710
TI  - The epidemiology of dermatologic and venereologic disease in a deployed
      operational setting.
AB  - We studied the epidemiology, morbidity, and etiology of dermatologic and non
      human immunodeficiency virus venereologic disease (Derm/STD) aboard a deployed
      aircraft carrier to revise Derm/STD training objectives for shipboard primary
      care providers. Onboard supplies for treatment of Derm/STD were also evaluated.
      Over 3 months, 929 Derm/STD patients were treated for 1,320 diagnoses generating
      2,011 visits. Derm/STD caused 22% of the total morbidity. Pyoderma alone
      accounted for nearly one-half of that morbidity and involved many work-center
      groups. Air wing, aircraft maintenance, and engineering work-center groups had
      lower burdens of pyoderma. Bacterial cultures were performed on 248 exudative
      dermatoses. Staphylococcus aureus was the dominant pathogen and was
      overwhelmingly sensitive in vitro to common, inexpensive antibiotics. Strategies
      to encourage prevention, earlier diagnosis, and rapid treatment of Derm/STD by
      deployed primary care providers are discussed.

PMID- 8754711
TI  - Communication survey of CH-47D crewmembers.
AB  - U.S. Army CH-47D cargo helicopter crewmembers are exposed to high levels of noise
      on a routine basis, yet must accomplish demanding missions that rely heavily on
      clear communication. This study looked at the auditory influences affecting
      communication by 17 crewmembers of a CH-47D Army Reserve unit. Results revealed
      (1) noise levels that exceed those of other Army rotary-winged aircraft, (2)
      different exposure levels for aviators and crewchiefs, (3) an overall preference
      for hearing "critical or diagnostic" aircraft sounds rather than wearing double
      hearing protection, (4) complaints of post-flight tinnitus or muffled hearing,
      (5) helmet discomfort among the majority of crewmembers, (6) a high incidence of
      hearing loss, (7) difficulties in adjusting radio volume controls for aviators,
      and (8) the effects of eyeglasses or protective masks on hearing and
      communications.

PMID- 8754712
TI  - Cold blood and clinical research during World War I.
AB  - Therapeutic transfusion was not a common procedure at the turn of the century.
      Although its safety was enhanced by the discovery of blood groups and preinfusion
      testing in the decade prior to World War I, techniques and indications remained
      cumbersome and clinically naive. By 1916, a stable Western Front, an efficient
      line of transport, and the operative requirements of a large number of wounded
      demonstrated the futility of pharmacotherapy or saline infusion for traumatic
      shock. In the same year, Rous and Turner at the Rockefeller Institute developed a
      preservative solution for whole blood. Rous' student, Dr. O.H. Robertson, arrived
      in France with Base Hospital 5 in June 1917 during a period of growing
      recognition by military surgeons that transfused blood was an effective therapy,
      although a practical delivery system was not available. Over the next 8 months,
      Robertson clinically tested a transfusion technique using preserved blood in
      glass jars carried to the front in specially designed cases. The method was
      accepted immediately, and by the Armistice transfusion was used frequently on the
      front line or during the perioperative period. The accessibility of preserved
      blood with an efficient transfusion system reinforced the introduction of
      "resuscitation teams" attached to Casualty Clearing Hospitals for the specialized
      management of traumatic shock. Robertson's success at technical innovation during
      World War I associated with a large clinical population resulted in the
      development of the indications and procedures for modern transfusion therapy.

PMID- 8754713
TI  - The evaluation of a managed dental delivery concept.
AB  - Phased dentistry (PD) is a philosophy of managed oral health care that emphasizes
      an orderly approach to dental risk assessment, prevention, and disease
      management. PD is divided into two stages. Phase I (PH1) care is intended to
      eliminate all conditions that may produce a dental emergency within 12 months.
      PH1 care is directed primarily to recruits and apprentice training students.
      Phase 2 (PH2) care strives to attain and maintain optimal oral health for Navy
      and Marine Corps personnel after their initial training period and throughout
      their military career. The purpose of this study was to evaluate the feasibility
      of introducing PH1 into a recruit dental treatment facility. Data were obtained
      at Naval Dental Center (NDC), Orlando from 4,571 recruit dental patients who were
      in-processed and completed recruit training between May 27 and October 1, 1993.
      The incoming operational dental readiness (ODR) of recruits during the PD trial
      was 28.5%, whereas the ODR of graduating recruits was 85.8%. During this same
      period there was a 34% increase in completed dental treatments per provider full
      time equivalent. Although dramatic increases in ODR and productivity were noticed
      during PD, other variables may have contributed to these results.

PMID- 8754714
TI  - Post-traumatic stress disorder symptoms among Gulf War veterans.
AB  - This study assessed the prevalence of risk for development of post-traumatic
      stress disorder (PTSD) symptoms among active duty and reserve veterans from
      Pennsylvania and Hawaii who either deployed (N = 1,524) or did not deploy (N =
      2,727) to the Persian Gulf as a result of Operation Desert Storm. All
      participants anonymously completed a survey questionnaire that included the
      Impact of Event Scale and the Brief Symptom Inventory. Results indicate the
      likelihood of PTSD symptoms in approximately 8.0% of active duty veterans and
      9.3% of reserve veterans who deployed to the Persian Gulf. PTSD risk comparisons
      are made with other active duty Army veterans assessed 1 year earlier. Sources of
      trauma are presented and implications for future military deployments on
      potential risks for developing PTSD are discussed.

PMID- 8754715
TI  - Nurse-physician communication: perceptions of nurses at an Army medical center.
AB  - The purposes of this study were to describe nurses' perceptions of their
      communication with physicians, as related to the openness of the communication,
      the accuracy of the information communicated, and the timeliness of the
      interaction; and further, to determine if specific demographic characteristics of
      nurses are associated with perceptions of positive communication. The sample (N =
      112) consisted of professional nurses working on one of nine inpatient units at a
      major military medical center. Shortell's ICU Nurse-Physician Communication
      subscale was used to measure the nurses' perceptions of the degree to which
      openness, accuracy, and timeliness described their communication with physicians.
      Overall findings were that the nurses perceived a poor quality of communication
      between themselves and the physicians with whom they interacted. Results from
      this study further indicated that the perceived quality of nurse-physician
      communication was not related to a nurse's educational level, length of nursing
      experience, or length of time assigned to a specific unit. Finally, findings
      provided no evidence that perceived levels of nurse-physician communication were
      greater among permanent staff than temporary nursing staff, or in intensive care
      units versus general ward areas.

PMID- 8754716
TI  - Parachuting injuries among Army Rangers: a prospective survey of an elite
      airborne battalion.
AB  - Injuries are common in sports and military parachuting. This paper presents
      results of a prospective survey of parachuting injuries in an airborne Ranger
      battalion. The Ranger regiment is the U.S Army's most elite airborne infantry,
      prepared for worldwide deployment without advanced notice. Average unit size was
      556 Rangers for the 18 months of follow-up. Other variables examined were type of
      landing area and time of day. During the follow-up period, all injuries occurring
      in the battalion were documented, as were all airborne operations. During the
      survey period, 65 airborne operations were conducted (7,948 static-line and free
      fall jumps), which caused 163 injuries to Rangers. Fifty-five percent of the
      operations and jumps were made at night, and 63, 23, and 14% of operations were
      onto fields, airports, and unimproved airplane landing strips, respectively. All
      operations were performed in a tactical environment with equipment. The "static
      line" injury rate was 2.2%. The types of injuries were similar to those found in
      previous reports. Dirt landing strips (4.7% injured) and airports (2.3%) appeared
      to be more hazardous landing areas than fields (1.6%) and water (0%), and more
      injuries occurred during night operations (2.7%) than during the day (1.4%). Two
      and one-half times as many severe injuries occurred at night versus day. This
      type of information is important for combat airborne operations.

PMID- 8754717
TI  - A retrospective analysis of the costs and consequences of a tobacco-cessation
      program for active duty service members.
AB  - Health system records of 126 active-duty (AD) service members who were
      participants in the Davis-Monthan AFB "Quitters are Winners" tobacco cessation
      program (QAWP) between June 1993 and May 1994 were reviewed retrospectively
      during the fall of 1994. Participants received an average of 2.84 (+/- 1.46)
      prescriptions for transdermal nicotine replacement therapy representing 6 weeks
      duration. Tobacco abstinence, determined by 6-month point prevalence abstinence
      (PPA), was 19.05 and 15.08% for 6-month continuous abstinence (CA). PPA and CA
      rates were significantly higher than expected (z = 3.94, p < 0.002; z = 2.38, p <
      0.02). Average operational cost per successful outcome at 6 months after entry
      into the QAWP were $778.93 using PPA and $983.92 using CA. Additional analyses
      revealed corresponding increases between average cost per successful outcome and
      duration of TNRT. This research provides an initial analysis of the efficiency of
      the QAWP for AD participants and a model for subsequent evaluations within
      military medical treatment facilities.

PMID- 8754718
TI  - Review of clinical use of sertraline by family practice physicians in a small Air
      Force hospital.
AB  - The clinical use of sertraline for 1 year in a family practice clinic in a small
      Air Force hospital was reviewed. Retrospective chart review showed that 85% of
      patients receiving five or more prescriptions for sertraline had a diagnosis of
      depression; the remainder were treated for chronic pain or dysthymia. The
      patients in the review needed dose increases (above the recommended starting dose
      of 50 mg qd) in nearly 50% of the cases. Clinicians using sertraline for the
      treatment of affective illness in the primary care setting should be aware of the
      likelihood for dose increases to achieve maximal clinical benefit.

PMID- 8754719
TI  - Hand-held dental X-ray (HDX) with medical collimator: use in casualty radiology.
AB  - The HDX X-ray machine can be used in military medicine, humanitarian missions,
      and training exercises. The equipment is useful for various radiographic
      examinations.

PMID- 8754720
TI  - Impact on USAF tuberculosis detection and control program given a low facility
      tuberculosis prevalence rate.
AB  - Isoniazid prophylaxis is a major part of the U.S. Air Force tuberculosis (TB)
      screening program and is closely tied to the efforts to eliminate TB. If a
      facility has a low prevalence rate of TB and there is no sound epidemiological
      evidence to rule out a false-positive TB skin test, a higher threshold for what
      constitutes a positive reaction in a given population may be appropriate.
      Criteria for preventive treatment in Air Force Instruction 48-115, para 3.4.2 and
      3.4.5, should be expanded to incorporate the positive-predictive rate of the
      tuberculin skin test as recommended by the Centers for Disease Control and
      Prevention.

PMID- 8754721
TI  - Cellulitis versus positive purified protein derivative? A case report and review
      of the literature.
AB  - The tuberculin skin test is one of the most widely used diagnostic aids ever
      developed and remains the only technique of detecting Mycobacterium tuberculosis
      infection other than actually culturing the organism. False-positives are an
      acknowledged problem, especially among health care workers (HCW), in whom
      rescreening can raise more questions than answers. A HCW presented with a severe
      response to an annual screening test and was retested 6 weeks later with normal
      results (non-reactive). Causes of false-positives (not including cross
      reactivity) are discussed. Readers of the purified protein derivative reaction
      need to consider alternative explanations for a significant response than
      infection with tuberculosis, given the medical history and nature of response.

PMID- 8754722
TI  - Unusual presentation of an osteoid osteoma.
AB  - We present a case of osteoid osteoma of the humerus diagnosed after it presented
      clinically as impingement syndrome. Clinical and magnetic resonance imaging data
      supported impingement, but standard non-surgical treatment did not provide
      complete pain relief. Subacromial injection resolved the anterior shoulder pain
      and unmasked medial arm and axillary pain. Humerus X-rays revealed a lytic
      diaphyseal lesion, and en-bloc resection of the humeral mass diagnosed an osteoid
      osteoma. This case is unusual in that only 1% of osteoid osteomas present in the
      humeral shaft. The clinical features and presentation of impingement and osteoid
      osteoma are discussed.

PMID- 8754723
TI  - [Incidence of fetal macrosomia: maternal and fetal morbidity].
AB  - The macrosomia is an obstetric eventuality associated to high maternal-fetal
      morbidity-mortality. This assay was planned in order to know the incidence of
      macrosomia in our institution, the relation between vaginal and abdominal
      deliveries and the fetal-maternal morbidity we reviewed 3590 records and we found
      5.6% incidence of macrosomia in the global obstetric population. There was 58% of
      vaginal deliveries, 68% of the newborn were male. The main complications were in
      the C. sections, 2 laceration of the hysterectomy, and 2 peroperative atonias. In
      the vaginal deliveries, the lacerations of III and IV grade were 9 of each grade.
      The main fetal complications were 5 slight to severe asphyxia and 4 shoulder
      dystocias. This assay concludes that the macrosomia in our service is similar to
      the already published ones, a 42% were C. section and the maternal-fetal
      morbidity was low.

PMID- 8754724
TI  - [Postoperative evaluation of different surgical procedures in genuine stress
      urinary incontinence: a retrospective study].
AB  - An evaluation of the surgical treatment for stress and mixed urinary incontinence
      and pelvic relaxation. One-year follow-up, was done. A retrospective study with
      144 files from the surgeries performed between February 1993 and June 1994, at
      the Clinica de Urologia Ginecologica del Instituto Nacional de Perinatologia. We
      excluded 37 files because of incomplete information. The age, parity, hormonal
      stage, preoperative diagnosis by urodynamic studies, surgical treatments and one
      year follow-up were analyzed. The mean age was 45.5 years. Pereyra procedure was
      performed in 53, Burch procedure in 47, anterior colporrhaphy in 5, and sling
      procedure in 2 patients. The incidence of complications was similar between the
      different groups. Resumption of spontaneous postsurgical voiding was delayed in
      the Pereyra group. The Burch urethropexy and Pereyra procedures were equally
      effective, with no statistical differences observed. Burch vaginal suspension was
      not more effective for the correction of urinary stress incontinence than Pereyra
      procedure.

PMID- 8754725
TI  - [Occurrence of pregnancy after microsurgical treatment of sterile patients with
      tubo-ovarian adhesive diseases].
AB  - In the last years, the adherence adnexal disease has been increased due to pelvic
      infections. This may cause infertility problems depending, of the nature,
      extension and localization inside the pelvis. In this paper we inform the results
      obtained in 70 patients with adnexal adhesions to whom it was performed a
      salpingo-ovariolysis with microsurgery technology, with the purpose of promote
      the fertility. All the patients received pre, trans and postoperative support
      (Heparin, steroids and antimicrobials). The minimal time of postoperative
      observation was at least 6 months. In 27 (Group I) of the 70 cases (38.6%), the
      adherences were avascular (IA & IIA based on Hulka's classification); and in the
      43 patients of the group II (61.4%), the lesions were dense and vascular (IB &
      IIB). In group I, 15 pregnancies were obtained (55.6%), 13 at term, 1 miscarriage
      and 1 ectopic pregnancy; in the group II we documented 9 pregnancies (20.9%), 5
      at term, 4 miscarriage (I trimester).

PMID- 8754726
TI  - [Is illegal abortion a secure procedure? A case report].
AB  - Woman with illegal abortion presenting bleeding and shock secondary to
      hypovolemia and sepsis. In the laparotomy there is no uterine perforation and the
      patient develops disseminated coagulation. The patient is taken to the operating
      room and bleeding stops. She receives more fluids than necessary and develops
      pulmonary edema. 48 hours after she develops shock secondary to tamponade and
      disappears with pericardiocentesis. A month and a half later she goes to the
      hospital because of ileus secondary to blood in peritoneo of an ovary cyst. Many
      pathologies and iatrogenesis characterized this case report.

PMID- 8754727
TI  - [Complications of radical hysterectomy during management of stage Ib and IIa
      cervix uteri cancer. Experience with 145 patients].
AB  - Perioperative morbidity and mortality were studied in 145 patients who underwent
      radical hysterectomy wit pelvic lymphadenectomy, as treatment of choice for
      cervical cancer, stages Ib and IIa at The Oncology Service on The General
      Hospital of Mexico, SSA, with special emphasis in urinary complications when
      superior bladder arteries were preserved, (99 cases) or not, (46 cases). There
      was no operative death. There were 20, (13.7%) intraoperative complications: 10
      (6.8%) injuries to hypogastric plexus; 5 (3.4%) ureteral sections and 2 (1.3%)
      injuries to iliac veins. Thirty nine patients, (26.8%) developed postoperative
      complications, (1 to 30 days): Bladder dysfunction, 30 (20.6%); wound infection,
      5 (3.4%); ureterovaginal fistula, 3 (2.0%) and vesicovaginal fistula, 3 (2.0%).
      After 30 days, we observed 5 complications, (3.4%): ureterovaginal fistula, 3
      (2.0); bowel obstruction, 1 (0.6%) and lymphocyst, 1 (0.6%). Surgical time was an
      hour longer, (4.15 hs vs. 3.15 hs) and bleeding increased a little bit, (1,125
      c.c. vs. 980 c.c.) when superior bladder arteries were preserved. However, in
      these cases, there were less postoperative complications, (29/99, 29.2% vs.
      19/46, 41.3%; P < 0.05), including ureterovaginal fistula, (1/99, 1.0% vs. 5/46,
      10.8%).

PMID- 8754728
TI  - [Current concepts on the course of pregnancies complicated by tuberculosis].
AB  - Tuberculosis is a public health problem in many countries, in the last ten years
      it has been a revival of this infection worldwide, including developed countries.
      Before chemotherapy emergency tuberculosis had a poor prognosis for the
      pregnancy, evolution change since the use of effective antituberculous drugs. In
      this moment if a pregnant woman receives a correct treatment, she will not
      experience an aggravation of the infection, nevertheless tuberculosis may cause
      an increase of the obstetric and neonatal mortality and morbidity rate, more
      frequently in women of developing countries or without treatment. Congenital
      tuberculosis is not frequent but is another risk for the newborns of tuberculous
      pregnant women.

PMID- 8754729
TI  - [Invasive studies at the office in the diagnosis of stress urinary incontinence].
AB  - A revision of the available diagnostic method is being made for the stress
      urinary incontinence, paying special attention to those which can be enhanced in
      the doctor's office. Three of the requiring catheters, endoscopic instruments or
      another kind of advices for his realization and they can be considered such as
      "Invasive test". There is mentioned that with these techniques there can be found
      an appropriate diagnosis of the genuine incontinence even up to a 75% of the
      cases. The remaining percentage requires studies either urodynamic or of any
      other kind in order to complete the diagnosis. The criterions are enlisted in
      order to send the patient to a specialized center.

PMID- 8754730
TI  - [Prevalence of fibrocystic disease of breast in patients with endometriosis].
AB  - The prevalence of fibrocystic breast disease in patients with endometriosis, was
      determined. This was a prospective cross-sectional study. The 43 women were
      diagnosed as having endometriosis by laparoscopy. In these patients, during their
      control period, a deliberate search for clinical and ultrasonography data on
      fibrocystic breast disease was carried out. The average age was 28 years, ranging
      between 18 and 36 years. From 43 the patients with endometriosis, 37% of them
      were diagnosed with fibrocystic breast disease. The group of age more frequent
      was between 30 and 34 years in 37.5%, and 31% between 20 and 24 years of age. 43%
      of the patients with both diseases had antecedent of pregnancy and 25% had
      menstrual alterations. The prevalence of fibrocystic breast disease in patients
      with endometriosis was 37%, thus observing a strong evidence of association
      between both pathologies.

PMID- 8754731
TI  - [Burial of Dr. don Alfonso Alvarez Bravo].

PMID- 8754732
TI  - Parathyroid hormone-related protein as a cardiovascular regulatory peptide.

PMID- 8754733
TI  - Cell-specific signal transduction of parathyroid hormone (PTH)-related protein
      through stably expressed recombinant PTH/PTHrP receptors in vascular smooth
      muscle cells.
AB  - PTH-related protein activates a G protein-coupled PTH/PTHrP receptor in many cell
      types and produces diverse biological actions. To study the signal transduction
      events associated with biological activity of the PTH/PTHrP receptor in vascular
      smooth muscle, a principal PTHrP-responsive tissue, rat aortic smooth muscle
      cells (A10) were stably transfected with a plasmid encoding a PTH/PTHrP receptor
      and tested for ligand binding, PTHrP-(1-34)-induced cAMP levels, inositol
      phosphate production, and cytosolic calcium transients. Of nineteen G418
      resistant lines recovered, all exhibited high affinity binding [approximately
      dissociation constant (Kd) > 10(-10)) of iodinated [Tyr36]hPTHrP(1-36)NH2 and
      ligand-induced cAMP accumulation (2- to 100-fold), which was directly
      proportional to PTH/PTHrP receptor number (range 4 x 10(3) to 7 x 10(7)
      sites/cell]. PTHrP had no effect on intracellular calcium or inositol phosphate
      formation in any cell line regardless of receptor number despite the presence of
      detectable G alpha q). Transient overexpression of individual G alpha q proteins
      (G alpha q, G alpha 11 or G alpha 14) into PTH/PTHrP receptor-expressing A10
      cells conferred the ability of PTHrP to increase intracellular calcium and
      inositol phosphate formation. Ligand activation of the recombinant PTH/PTHrP
      receptor elicited appropriate downstream biological effects in A10 cells
      including inhibition of DNA synthesis and osteopontin messenger RNA (mRNA)
      expression. Thus, a single PTH/PTHrP receptor, though capable of coupling to
      different G proteins, signals exclusively through a cAMP-dependent pathway in
      vascular smooth muscle.

PMID- 8754734
TI  - Thyroid-stimulating hormone inhibits Fas antigen-mediated apoptosis of human
      thyrocytes in vitro.
AB  - The mechanisms of TSH-induced growth stimulation of thyrocytes in vivo have yet
      to be elucidated. We examined the antiapoptotic effect of TSH toward Fas antigen
      mediated apoptosis of thyrocytes. Fas antigen was expressed on approximately 40%
      of unstimulated thyrocytes, and the expression was significantly inhibited by the
      addition of TSH in a dose-dependent manner. Treatment of thyrocytes with 8-bromo
      cAMP mimicked the effect of TSH, suggesting that the inhibitory effect of TSH on
      Fas antigen expression was mediated by activating protein kinase A. In contrast,
      treatment of thyrocytes with either interleukin-1 beta (IL-1 beta) or interferon-
      gamma (IFN gamma) markedly increased Fas antigen expression on thyrocytes, and
      these effects were inhibited in the presence of TSH. The expression of the
      protooncogene product Bcl-2 did not change after the addition of TSH, 8-bromo
      cAMP, IL-1 beta, IFN gamma, or a combination of TSH and IL-1 beta or IFN gamma.
      When thyrocytes stimulated with either IL-1 beta or IFN gamma were treated with
      anti-Fas IgM mAb, the cells were committed to apoptosis, whereas this apoptotic
      process was significantly inhibited by the addition of TSH. These results
      indicate that the Fas antigen is functionally expressed on the surface of
      thyrocytes, and TSH inhibits Fas antigen-mediated apoptosis of thyrocytes through
      the inhibitory effect of Fas antigen expression, resulting in the promotion of
      growth of the thyroid gland.

PMID- 8754735
TI  - Increased cyclic adenosine 3',5'-monophosphate inhibits G protein-coupled
      activation of phospholipase C in rat FRTL-5 thyroid cells.
AB  - Thyroid cell growth and function are regulated by several hormones and growth
      factors that bind to cell surface receptors coupled via G proteins, Gs and Gq, to
      stimulation of adenylyl cyclase and phospholipase C (PLC), respectively. We
      created a permanently transfected FRTL-5 cell line (TG8) in which the
      thyroglobulin gene promoter directs expression of the cholera toxin (CT) A1
      subunit (CTA1). CTA1 catalyzes ADP ribosylation of Gs alpha, which results in
      persistent activation of Gs alpha. Activated Gs alpha causes constitutive
      stimulation of adenylyl cyclase and increases levels of intracellular cAMP.
      Because G protein-coupled signaling pathways exhibit cross-talk, we compared TG8
      cells to FRTL-5 cells transfected with the neomycin resistance gene (TG4) to
      determine whether constitutive stimulation of adenylyl cyclase influences the PLC
      pathway. PLC activity was assessed by measuring levels of total inositol
      phosphates (IPs) in TG4 and TG8 cells that had been preincubated with myo
      [3H]inositol for 2 days. Baseline values of [3H]IP production were similar for
      the two cell lines. Incubation of TG4 control cells with 10(-8) M TSH, 300 microM
      ATP, and 100 microM norepinephrine for 60 min stimulated 2.5-, 8.1-, and 3.4-fold
      increases, respectively, in [3H]IP production over the control value. By
      contrast, there was no [3H]IP response to any of these ligands in TG8 cells. TG8
      cells exhibit a decrease in [35S]adenosine 5'-(gamma-thio)triphosphate binding to
      their cell surface compared to TG4 control cells counterparts, but no decrease in
      [125I]TSH binding. Treatment of TG4 cells with 100 ng/ml CT, 50 microM forskolin,
      or 1 mM 8-bromo-cAMP for 2 days reproduced the loss of ligand-stimulated [3H]IP
      synthesis present in TG8 cells. Although levels of immunoreactive Gq alpha and Gq
      alpha 11 were normal in TG8 cells, sodium fluoride-induced [3H]IP production was
      also inhibited. Levels of immunoreactive PLC beta 3, the dominant subtype of PLC
      beta in FRTL-5 cells, were not altered in TG8 cells or by CT treatment of TG4
      cells. These data indicate that elevated levels of cAMP can inhibit the activity
      of G protein-coupled PLC. Further study of this model will elucidate our
      understanding of the exact mechanism responsible for this interaction.

PMID- 8754736
TI  - Potent neuropeptide Y Y1 receptor antagonist, 1229U91: blockade of neuropeptide Y
      induced and physiological food intake.
AB  - Neuropeptide Y (NPY) is thought to increase food intake through the action of Y1
      (-like) receptors in the hypothalamus. To confirm the involvement of Y1 receptors
      in feeding behavior, selective and potent antagonists for Y1 receptors are
      required. In the present study, we showed that a peptide, 1229U91
      [(Ile,Glu,Pro,Dpr,Tyr,Arg,Leu,Arg, Tyr-NH2)2 cyclic (2,4'),(2',4)-diamide], is a
      potent and selective antagonist for Y1 receptors. 1229U91 displaced [125I]peptide
      YY (PYY) binding to membranes of human neuroblastoma-derived SK-N-MC cells that
      predominantly express Y1 receptors with a K1 value 0.10 nM and inhibited the NPY
      induced increase in intracellular calcium levels(IC50 = 0.27 nM). In contrast,
      the K1 values for [125I]PYY binding to Y2 receptors in membranes of human
      neuroblastoma-derived SK-N-BE2 cells and rat hypothalamus were 700 nM and more
      than 1 microM, respectively. Although [125I]PYY could not detect Y1 receptors in
      the rat hypothalamic membranes, [125I]1229U91 revealed binding sites with a high
      affinity (Kd = 18 pM), indicating the presence of Y1 receptors in the
      hypothalamus. Intracerebroventricular injection of 1229U91 (30 micrograms) into
      male Sprague-Dawley rats completely inhibited NPY (5 micrograms)-induced food
      intake without any other behavioral change. Furthermore, intracerebroventricular
      injection of 1229U91 significantly suppressed physiological feeding behavior
      after overnight fasting. These results indicate that Y1 receptors in the rat
      hypothalamus mediate NPY-induced food intake, and that physiological feeding
      behavior after overnight fasting may be largely regulated by NPY via Y1
      receptors. 1229U91 may be useful for further elucidating the pathophysiological
      roles of NPY in feeding behavior.

PMID- 8754737
TI  - Paraventricular norepinephrine release mediates glucoprivic suppression of
      pulsatile luteinizing hormone secretion.
AB  - Restriction of glucose availability by 2-deoxyglucose (2DG) suppresses pulsatile
      LH release. The aim of the present study was to determine whether norepinephrine
      (NE) release in the paraventricular nucleus (PVN) is involved in the glucoprivic
      suppression of LH secretion in ovariectomized rats. Twelve days after
      ovariectomy, animals were stereotaxically implanted with a guide cannula for
      microdialysis in the PVN. Two days later, the PVN was perfused continuously with
      Ringer's solution or Ringer's solution containing a catecholamine synthesis
      inhibitor, alpha-methyl-p-tyrosine (100 microM), through a microdialysis probe
      inserted in the guide cannula 2 h before the beginning of sampling, which lasted
      3 h. Blood samples were collected every 6 min through an atrial cannula, and
      dialysates were collected every 20 min. One hour after the beginning of sampling,
      2DG (400 mg/kg BW) was administered iv through the atrial cannula.
      Paraventricular NE levels significantly increased immediately after 2DG injection
      (P < 0.05), and both mean LH concentrations and the frequency of LH pulses
      decreased. By contrast, when alpha-methyl-p-tyrosine was administered into the
      PVN, 2DG did not produce an increase in paraventricular NE, and no depression of
      LH secretion occurred. These results suggest that the PVN mediates the
      glucoprivic suppression of LH pulses via the release of NE.

PMID- 8754738
TI  - Differential modulation of thyroid hormone responsiveness by retinoids in a human
      cell line.
AB  - Previous studies have suggested that there is an interrelationship between
      responses mediated by retinoic acid (RA) and those to thyroid hormone (T3). These
      experiments have used transfected gene constructs, often in receptor-negative
      cells. To study the relationship between RA- and T3-mediated responses in intact
      human cells, we incubated HepG2 cells for 4 days in serum-free medium with T3
      and/or RA or 9-cis-RA. Measured responses were stimulation of secreted sex
      hormone-binding globulin (SHBG) or inhibition of secreted T4-binding globulin
      (TBG). T3 induced a dose-responsive increase in SHBG secretion that was maximal
      at 10nM (206 +/- 24% of untreated value) and half-maximal at 0.36 +/- 0.16 nM T3.
      RA and 9-cis-RA, up to 100 nM, induced a slight fall in SHBG secretion to 79 +/-
      9% and 88 +/- 9%, respectively. T3 induction of SHBG secretion was significantly
      attenuated in cells coincubated with T3(0-10nM) and RA. With T3 (10 nM) together
      with RA (3, 10, or 100 nM), the maximal SHBG responses were reduced to 193 +/-
      24%, 151 +/- 5% and 132 +/- 30%, respectively. With T3 and 9-cis-RA (100 nM),
      maximal stimulation was 169 +/- 20%. Importantly, the effective half-maximal
      stimulatory concentration of T3 in the presence of either retinoid (3-100 nM) was
      unchanged at 0.3 nM T3. In addition, the inhibitory effect of 9-cis RA could not
      be overcome even with 300 nM T3. The threshold for the RA effect was between 0.3
      1 nM, with half-maximal inhibition at 30 nM. 9-cis-RA was approximately 10-fold
      less potent than RA. Preliminary studies suggested that changes in SHBG messenger
      RNA levels were similar to those in secreted SHBG. No effect was observed with
      vitamin D or clofibrate, either alone or combined with T3. Conversely, T3 reduced
      TBG secretion, with maximal suppression to 74 +/- 5% of the control value at a T3
      concentration of 10 nM. RA alone reduced TBG secretion to 76% of the control
      value. RA did not attenuate the effect of T3, and the two agents combined showed
      no synergism. Neither T3 nor RA, alone or in combination, influenced secreted
      total protein or albumin. RA did not alter the concentration of nuclear T3
      binding sites. These data suggest that retinoids act via a gene-dependent
      mechanism to modulate maximal, but not half-maximal, responses to T3 in HepG2
      cells with the specificity of RA greater than that of 9-cis-RA.

PMID- 8754739
TI  - Glucagon response to hypoglycemia is improved by insulin-independent restoration
      of normoglycemia in diabetic rats.
AB  - The aim of this study was to determine whether the impaired glucagon response to
      insulin-induced hypoglycemia in the diabetic rat can be improved by correction of
      hyperglycemia independent of insulin. Four groups of age-matched male Sprague
      Dawley rats (246 +/- 13 g BW) were studied: 1) normal controls (NC; n = 7); 2)
      diabetic, untreated (DU; n = 6); 3) diabetic, treated for 5-7 days using
      sustained release (2-3 U/day) insulin implants (DI; n = 6); and 4) diabetic,
      treated for 3-4 days with phlorizin (0.4 g/kg), given sc twice daily (DP; n = 7).
      Diabetes was induced by a single injection of streptozotocin (65 mg/kg). Basal
      plasma glucose was 7.4 +/- 0.3 mM in NC, but rose to 14.5 +/- 2.2 mM in DU. Basal
      hyperglycemia was corrected with phlorizin and insulin treatments (5.5 +/- 0.5
      and 6.7 +/- 0.8 mM, respectively). NC rats responded to insulin-induced
      hypoglycemia with a rapid and marked increase in glucagon (peak, 2059 +/- 311
      pg/ml). The glucagon response was blunted in DU (635 +/- 180 pg/ml) and was
      partially improved by prolonged normalization of glycemia in DP (1335 +/- 295
      pg/ml; P < 0.05). Plasma somatostatin levels in all diabetic groups were 2- to 3
      fold higher in the basal state, but were not different during hypoglycemia, than
      those in NC rats. Compared to levels in NC rats, diabetes resulted in decreased
      insulin, but elevated glucagon and somatostatin concentrations in the pancreatic
      tissue. Treatment with both insulin and phlorizin reversed the changes in the
      pancreatic content of both glucagon and somatostatin. Pancreatic proglucagon
      messenger RNA did not show significant differences among the four groups in
      either state. Insulin treatment in the DI group resulted in a delayed and much
      smaller increase in the glucagon response (740 +/- 138 pg/ml) to hypoglycemia
      despite normalization of glycemia. We, therefore, conclude that in streptozotocin
      diabetic rats, the impaired glucagon responsiveness to hypoglycemia is
      significantly improved by insulin-independent correction of hyperglycemia,
      suggesting the importance of normoglycemia per se in maintaining, at least in
      part, the glucose sensitivity of pancreatic alpha-cells.

PMID- 8754740
TI  - Differentiation of rat preadipocytes is accompanied by expression of thyrotropin
      receptors.
AB  - To investigate the regulation of expression of the TSH receptor (TSHR) in
      extrathyroidal tissues, the level of TSHR messenger RNA (mRNA) and TSH-dependent
      signal transduction were determined in isolated rat adipocytes and cultured
      preadipocytes. The epididymal, sc, and perirenal, but not the interscapular brown
      adipose tissues, possessed TSHR mRNA and increased cAMP responses to TSH and were
      thus used as the source of preadipocytes. Morphological analysis revealed that
      the combination of insulin and T3 most effectively caused the differentiation of
      rat preadipocytes. These differentiated preadipocytes exhibited increased cAMP
      production in response to TSH. The addition of FCS to the culture medium
      inhibited the differentiation of rat preadipocytes as well as TSH-stimulated
      production of cAMP. The stimulation of differentiation was associated with an
      increased expression of TSHR mRNA levels, whereas the inhibition of
      differentiation was associated with a decreased expression of TSHR mRNA, as
      detected by Northern blot analysis. The results indicate that the expression and
      function of the TSHR in cultured rat preadipocytes are closely related to
      cellular differentiation. Cultured rat preadipocytes appear to provide a useful
      system for studying the mechanism of extrathyroidal expression of TSHR.

PMID- 8754741
TI  - A proteolytic fragment of insulin-like growth factor (IGF) binding protein-3 that
      fails to bind IGFs inhibits the mitogenic effects of IGF-I and insulin.
AB  - Limited proteolysis of insulin-like growth factor binding protein-3 (IGFBP-3) is
      increasingly becoming recognized as an essential mechanism in the regulation of
      insulin-like growth factor (IGF) bioavailability, both in the bloodstream and at
      cellular level. Plasmin generated on contact with various cell types provokes
      proteolytic cleavages that are similar to those induced in vivo by (as yet
      unidentified) IGFBP-3 proteases. Experimental conditions were determined to
      achieve plasmin-induced limited proteolysis of recombinant human nonglycosylated
      IGFBP-3. Two major fragments of 22/25 kilodaltons (kDa) and one of 16 kDa were
      identified by Western immunoblotting and isolated by reverse-phase
      chromatography. The 22/25-kDa fragments correspond to the major approximately 30
      kDa glycosylated fragment of IGFBP-3 in serum and the 16-kDa fragment, to one of
      the same size, that is nonglycosylated. Western ligand blot analysis, affinity
      cross-linking, and competitive binding experiments using radiolabeled IGF and
      unlabeled IGF-I or -II showed that in the high performance liquid chromatography
      eluate containing the 16-kDa fragment, all affinity for IGFs had been lost,
      whereas the affinity of the 22/25-kDa fragments was considerably reduced.
      Scatchard analysis of the data indicated a 20-fold loss of affinity for IGF-II
      and an 50-fold loss for IGF-I compared with that of recombinant human IGFBP-3. In
      a chick embryo fibroblast assay in which DNA synthesis was stimulated both by IGF
      I and by insulin (at 100-fold concentrations, so that interaction with the Type 1
      IGF receptor would occur), IGFBP-3 was found to inhibit IGF-I-induced stimulation
      almost totally. It had no effect on stimulation by insulin, which has no affinity
      for the IGFBPs. With the 22/25-kDa fragments, barely 50% inhibition of IGF-I
      stimulation was achieved and no inhibition of insulin stimulation. Unexpectedly,
      with the fraction containing the 16-kDa fragment (despite the total lack of
      affinity for IGF-I), IGF-I-induced stimulation was inhibited to nearly the same
      extent as with intact IGFBP-3. In addition, insulin-induced stimulation was
      inhibited with similar potency. IGFBP-3 proteolysis therefore generates two types
      of fragment with different activities. One has weak affinity for IGF-I and is
      only a weak antagonist of IGF action. The other lacks affinity for the IGFs, but
      nevertheless inhibits IGF-stimulated mitogenesis, thus acting by a mechanism that
      is independent of the IGFs.

PMID- 8754742
TI  - Relationships among sex steroids, oxytocin, and their receptors in the rat uterus
      during late gestation and at parturition.
AB  - Sex steroids and oxytocin (OT) produced within intrauterine tissues have been
      implicated in the regulation of parturition. The purpose of these studies was 1)
      to determine the relationships among estradiol (E2), progesterone (P4), OT, and
      their receptors in uterine tissues during late gestation and parturition in the
      rat; 2) to observe the effects of the estrogen antagonist tamoxifen (TAM) on
      these factors; and 3) to evaluate the rat as a potential model for events at
      human parturition. Concentrations of E2, P4, PGE2, and OT were measured by RIA.
      E2 receptor (ER) was measured by enzyme immunoassay, and P4 receptor (PR) and OT
      receptor (OTR) were measured by binding assays. OT messenger RNA (mRNA) was
      measured by ribonuclease protection assay. Groups (n = 5) of pregnant rats
      (normal gestation = 22 days) were treated with TAM (200 mg/day) or vehicle and
      killed on gestation day 19, 21, 21.5, or 22 or after delivery of the first pup.
      Serum E2 increased throughout late gestation accompanied by an increase in
      uterine OT mRNA and ER. Serum P4 declined after day 19, and uterine PR did not
      change significantly. Uterine PGE2 increased progressively, reaching peak levels
      the evening before delivery. Uterine OTR did not increase until the morning of
      delivery, and uterine OT peptide concentrations increased only during
      parturition. Parturition was significantly delayed by 24 h in the TAM-treated
      group. TAM inhibited the increase in serum E2, uterine ER, and OT mRNA and
      peptide, but had no effect on serum P4 or uterine PR levels. With TAM, the
      responses of uterine OTR and PGE2 were significantly delayed, but still underwent
      a significant increase before the delayed parturition. These results support the
      hypothesis that E2 stimulates the synthesis of ER, OT, and OTR within the rat
      uterus and is essential for normal parturition. P4 withdrawal may be more
      important to the increases in OTR and PGE2, but these are delayed in the absence
      of estrogen. These data also suggest that the rat may be a relevant model for
      human parturition.

PMID- 8754743
TI  - Sexual dimorphism of steroid hormone receptor messenger ribonucleic acid
      expression and hormonal regulation in rat vascular tissue.
AB  - Evidence has accumulated suggesting that steroid hormones have a direct effect on
      the vascular system. Of special interest is the protective effect of estrogens
      against cardiovascular diseases. One of the aims of the present study was to
      investigate the messenger RNA (mRNA) expression of the five classic steroid
      hormone receptors in the great vessels of the rat (aorta, vena cava, and vena
      portae) to provide a basis to analyze direct steroid effects on vascular tissue.
      By applying reverse transcription-PCR we compared the expressions of the steroid
      hormone receptor mRNAs in the respective vessels of male and female rats. Sex
      differences in the mRNA levels of the mineralocorticoid (MR), estrogen (ER), and
      progesterone (PR) receptors were found in venous vessels, but not in the aorta.
      Focussing on the vena cava in the female rat, we investigated whether the ER is
      active in the vasculature by analyzing regulation of the PR gene. This gene is
      known to be regulated by estrogens in classic target organs. PR mRNA expression
      in venous vessels of female rats decreased after ovariectomy. This effect was
      reversed by chronic sc treatment with estradiol (E2; 1 microgram/animal day).
      Progester-one (10 mg/animal day, sc) partly inhibited the effect of E2. Besides
      E2, the partial agonist tamoxifen stimulated PR mRNA expression in ovariectomized
      rats, whereas the pure antiestrogen ZM 182780 remained inactive in this
      experiment. Both E2 and tamoxifen caused an autologous down-regulation of ER
      mRNA. In conclusion, our study demonstrates for the first time that not only the
      aorta, but also the venous vessels, represented by the vena cava and the portal
      vein of the rat, are targets for steroid hormones. The ER in vascular tissue is
      functionally active and mediates direct modulatory effects of estrogens on gene
      expression in vascular cells.

PMID- 8754744
TI  - Isoform-specific 3,5,3'-triiodothyronine receptor binding capacity and messenger
      ribonucleic acid content in rat adenohypophysis: effect of thyroidal state and
      comparison with extrapituitary tissues.
AB  - Although the role of the three functional thyroid hormone receptor isoforms (TR
      beta 1, TR beta 2, and TR alpha 1) remains unclear, studies by Hodin and Lazar et
      al. have suggested that restriction of TR beta 2 messenger RNA (mRNA) to rat
      pituitary could reflect a specific regulatory role in the pituitary. Supporting
      their hypothesis was a significant fall in pituitary TR beta 2 mRNA after T3
      administration. These observations prompted us to assess the effect of thyroidal
      state on the level of TR beta 2 protein, as inferred by immunoprecipitation of TR
      beta 2 nuclear binding activity. In contrast to the behavior of the mRNA, we
      noted surprising stability in the levels of total nuclear TR binding capacity and
      TR isoform distribution in the transition from hypo- to hyperthyroid states.
      Calculations based on these and previous data from this laboratory (7) show that
      the average cellular content of TR beta 2 mRNA in pituitary is 0.6 molecules,
      whereas the content of TR beta 2 mRNA molecules in extrapituitary tissues is less
      than 0.007 molecule/cell. A high TR beta 2 protein/mRNA ratio in extrapituitary
      tissues thus could reflect a rapid turnover of TR beta 2 mRNA compared to TR beta
      2 protein. This would explain the widespread distribution of TR beta 2 protein
      and the scarcity of mRNA in extrapituitary tissues.

PMID- 8754745
TI  - Gonadotropins induce rapid phosphorylation of the 3',5'-cyclic adenosine
      monophosphate response element binding protein in ovarian granulosa cells.
AB  - The pituitary gonadotropins FSH and LH exert their effects on gonadal target
      cells, at least in part, through the activation of adenylyl cyclase and the
      production of the second messenger cAMP. To elucidate further the signal
      transduction pathways regulating gonadotropin-responsive genes in ovarian
      granulosa cells, we have investigated the expression of the cAMP response element
      binding protein (CREB), which mediates many of the effects of cAMP by modulating
      the transcription of target genes in a cAMP-dependent fashion. In situ
      hybridization, RNA blot analysis and RT-PCR RNA quantification demonstrated that
      CREB messenger RNA (mRNA) is expressed at low levels throughout the ovary, and
      that CREB mRNA levels do not change appreciably after gonadotropin stimulation.
      Similar results were obtained using immunohistochemistry and Western protein
      blotting to examine CREB protein in ovaries isolated from immature animals
      treated with gonadotropins or immunocytochemistry and Western protein blotting to
      examine the CREB protein in cultured granulosa cells after gonadotropin
      treatment. In contrast, immunocytochemistry and Western protein blotting using an
      antipeptide antibody specific to CREB phosphorylated at serine 133 (P-CREB),
      which is the activated from of the CREB protein, revealed a dramatic increase in
      the phosphorylated form of CREB within 20 min of gonadotropin treatment of
      granulosa cells that was transient and was decreased by 60 min after gonadotropin
      treatment. Stimulation of P-CREB was observed using granulosa cells isolated from
      immature animals and treated with recombinant human FSH in vitro, or using
      granulosa cells isolated from immature animals primed with PMSG in vivo and
      treated with human CG (hCG) in vitro. Stimulation of P-CREB was also observed in
      ovarian granulosa cells isolated from animals treated with PMSG in vivo. These
      results indicate that both gonadotropins can induce a rapid and transient
      phosphorylation of the CREB protein in granulosa cells, leading to the activation
      of a factor likely to play an important role in the transcription of many
      gonadotropin-regulated ovarian genes.

PMID- 8754746
TI  - Estradiol-induced diurnal changes in lactotroph proliferation and their
      hypothalamic regulation in ovariectomized rats.
AB  - Pentobarbital anesthesia during the proestrous afternoon delays proliferation of
      lactotrophs of the anterior pituitary from estrus to diestrus 1 in cycling female
      rats. We determined whether estradiol treatment induced diurnal changes in rates
      of lactotroph proliferation in ovariectomized rats, and if so, examined whether
      hypothalamic neural activity was involved in the occurrence of the estradiol
      induced diurnal changes. Dispersed anterior pituitary cells were obtained from
      ovariectomized rats bearing estradiol implants that had been treated with 5-bromo
      2'-deoxyuridine (BrdU) 3 h before decapitation. BrdU-labeling indices
      representative of the proliferation rate of lactotrophs were determined by double
      immunofluorescence staining for BrdU and PRL. After treatment of ovariectomized
      rats with estradiol on day 0, BrdU-labeling indices of lactotrophs as determined
      by injecting BrdU at 1000 h increased markedly with time peaking on days 4-7.
      Levels of BrdU-labeling indices at 1000 h on day 4 were 2.8-fold higher than
      those at 2200 h on day 3 or 4 after estradiol treatment. However, levels of BrdU
      labeling indices at 1000 h on day 14 were 35% lower than those at the same time
      on day 4 and did not differ from those at 2200 h on day 13 or 14. In addition, a
      difference in BrdU-labeling indices as observed between 1000 and 2200 h on day 4
      in the ovariectomized rats was not detected in estradiol-treated orchidectomized
      male rats. Serial determinations of BrdU-labeling indices throughout day revealed
      that the difference in BrdU-labeling indices between 1000 and 2200 h on day 4 in
      the ovariectomized rats reflected estradiol-induced diurnal changes that were
      characterized by a peak between 0700-0900 h and a nadir between 1900-2200 h.
      Pentobarbital injected at 0900 or 2100 h on day 3 decreased slightly high levels
      of BrdU-labeling indices at 0800 h on day 4. However, pentobarbital injection at
      1345 h on day 3, which was effective in blocking estradiolinduced surges of LH
      and PRL secretion, suppressed markedly the high levels at 0800 h on day 4. In
      these pentobarbital-blocked rats, the diurnal changes in BrdU-labeling indices
      whose peak would normally have occurred at 0700-0900 h on day 4 were delayed not
      by the time corresponding to the duration of pentobarbital anesthesia but exactly
      by 24 h. These results suggest that 1) hypothalamic and sexually dependent
      diurnal changes in lactotroph proliferation can be induced by short-term
      estradiol treatment in ovariectomized rats as well as in cycling rats, and 2)
      estradiol treatment for 14 days rather prevents the diurnal changes in lactotroph
      proliferation.

PMID- 8754747
TI  - Regulation of somatic growth and the somatotropic axis by gonadal steroids:
      primary effect on insulin-like growth factor I gene expression and secretion.
AB  - The site-specific regulation of somatic growth by sex steroids is poorly
      understood. The aim of the present study was to assess the influence of 17 beta
      estradiol (E2) and 5 alpha-dihydrotestosterone (DHT) on somatic growth and
      pituitary GH and hepatic insulin-like growth factor I (IGF-I) secretion and
      synthesis in the adult female rat. Animals (200-250 g) underwent sham surgery or
      bilateral ovariectomy. Some ovariectomized (OVX) rats were given sc implants that
      provided almost physiological female E2 (OVX/E2) and male DHT (OVX/DHT) levels.
      Animals were killed 3, 7, 14, and 26 days later. Body weight gain was calculated,
      and pituitary GH content, pituitary GH messenger RNA (mRNA) levels, plasma GH,
      and circulating IGF-I concentrations were measured. Levels of hepatic IGF-I mRNA
      were measured at 26 days. Ovariectomy increased body weight gain (P < 0.001) in
      parallel with a significant elevation in plasma IGF-I (P < 0.001). Replacement of
      E2 markedly suppressed somatic growth (P < 0.001), plasma IGF-I concentrations (P
      < 0.001), and liver IGF-I gene expression (P < 0.002). However, circulating GH
      concentrations were high in OVX/E2 animals (P < 0.001), whereas pituitary GH
      stores were significantly attenuated (P < 0.05). In contrast, DHT exposure
      increased body weight gain (P < 0.001), circulating IGF-I concentrations (P <
      0.05), and steady state hepatic IGF-I mRNA levels (P < 0.05). Pituitary GH stores
      were markedly elevated (P < 0.001) in DHT-treated animals, but circulating GH
      levels remained very low. Pituitary GH mRNA rose transiently at 7 days in OVX and
      OVX/E2 rats, but no consistent changes between the groups were observed
      thereafter. We conclude that 1) gonadal steroids have disparate effects on
      somatic growth in female rats, with E2 suppressing and DHT stimulating body
      weight gain; 2) these effects are likely to be primarily mediated at the level of
      IGF-I synthesis and secretion; and 3) changes in pituitary GH content and
      secretion probably reflect normal adjustment to changes in the intensity of IGF-I
      negative feedback.

PMID- 8754748
TI  - Adrenomedullin inhibits feeding in the rat by a mechanism involving calcitonin
      gene-related peptide receptors.
AB  - The central effect of adrenomedullin on feeding was investigated in fasted rats.
      After intracerebroventricular administration, adrenomedullin decreased 2-h food
      intake in a dose-dependent manner. A dose of 1.7 nmol adrenomedullin decreased 2
      h food intake by 57%. Adrenomedullin shares sequence homology with calcitonin
      gene-related peptide (CGRP), a central anorectic agent, and binding sites for
      both are present in the hypothalamus. Adrenomedullin competed for
      [125I]adrenomedullin- and [125I]CGRP-binding sites in hypothalamic membranes. The
      Kd for the [125I]adrenomedullin-binding site was 0.54 +/- 0.07 nM, with a binding
      capacity of 214 +/- 27 fmol/mg membrane protein (n = 3). CGRP and the CGRP
      receptor antagonist CGRP-(8-37) at concentrations up to 1 microM did not compete
      at these sites. The Kd for the CGRP-binding site was 0.10 +/- 0.02 nM, with a
      binding capacity of 250 +/- 31 fmol/mg, and the Ki values for adrenomedullin and
      CGRP-(8-37) were 4.6 +/- 2.1 and 4.0 +/- 1.6 nM, respectively (n = 3). Thus,
      adrenomedullin showed high affinity binding at both adrenomedullin- and CGRP
      binding sites. To establish whether adrenomedullin reduces feeding via CGRP
      receptors, we coadministered adrenomedullin (1.7 nmol) and CGRP-(8-37) (30 nmol).
      The reduction in 2-h food intake induced by adrenomedullin was 50% inhibited by
      CGRP-(8-37). These results show that adrenomedullin decreases food intake in the
      rat, and this effect is mediated at least in part via CGRP receptors.

PMID- 8754750
TI  - Specific nuclear localization of 11-dehydrocorticosterone in rat colon: evidence
      for a novel corticosteroid receptor.
AB  - When colonic crypt cells isolated from intact rats are incubated with
      [3H]corticosterone specific nuclear binding is displaced by neither aldosterone
      nor the antiglucocorticoid RU38486, suggesting that [3H]corticosterone is binding
      to a site distinct from classical mineralocorticoid and glucocorticoid receptors.
      TLC revealed that the predominant nuclear [3H]steroid in the nucleus of
      [3H]corticosterone-incubated colonic crypt cells is [3H]11-dehydrocorticosterone.
      Where the enzyme 11 beta-hydroxysteroid dehydrogenase converting corticosterone
      to 11-dehydrocorticosterone is absent (cytosol preparations), [3H]corticosterone
      binds to classical glucocorticoid and mineralocorticoid receptors; in whole cells
      when 11 beta-hydroxysteroid dehydrogenase is blocked by carbenoxolone,
      cytoplasmic and nuclear binding of authentic [3H]corticosterone rises. Saturation
      and Scatchard analyses of nuclear [3H]11-dehydrocorticosterone binding
      demonstrate a single saturable binding site with a dissociation constant of < or
      = 10 nM at 22 C. We interpret these studies as evidence for a novel 11
      dehydrocorticosterone-preferring receptor that may mediate glucocorticoid effects
      in tissues with high level of 11 beta-hydroxysteroid dehydrogenase activity.

PMID- 8754749
TI  - Retinoids increase cell-cell adhesion strength, beta-catenin protein stability,
      and localization to the cell membrane in a breast cancer cell line: a role for
      serine kinase activity.
AB  - In this study we show that a breast cancer cell line (SKBR3) that expresses no E
      cadherin and very low levels of beta-catenin protein and exhibits a poorly
      adhesive phenotype in Matrigel responds to retinoic acid (RA) by a marked
      increase in epithelial differentiation. Specifically, treatment of cells with all
      trans-RA, 9-cis-RA, or a RA receptor alpha-specific ligand resulted in a large
      increase in cell-cell adhesive strength and stimulated the formation of fused
      cell aggregates in Matrigel. A retinoid X receptor-specific ligand was
      ineffective. Exposure of cells to 9-cis-RA for as little as 4 h was sufficient to
      maintain the adhesive phenotype for at least 4 days. The effects of 9-cis-RA
      required protein and RNA synthesis, but were not mediated by factors secreted by
      stimulated cells or by direct cell contact and did not require serum. These 9-cis
      RA-induced morphological effects were completely reversed by growing cells in 50
      microM Ca2+, suggesting a mechanism involving a 9-cis-RA-induced increase in
      Ca(2+)-dependent adhesion. Consistent with this, beta-catenin protein levels were
      markedly elevated in the 9-cis-RA-treated cells, and beta-catenin became
      localized to a Triton-insoluble pool at regions of cell-cell contact. No change
      could be detected in beta-catenin steady state messenger RNA levels, but 9-cis-RA
      did increase beta-catenin protein stability. Treatment of cells with low calcium
      medium did not prevent the 9-cis-RA-induced increase in total beta-catenin
      protein, but did prevent its movement to a Triton-insoluble pool at the cell
      membrane. Among several kinase inhibitors, only the broad spectrum kinase
      inhibitor staurosporine and the protein kinase C inhibitor bisindoylmaleimide
      reversed the morphological changes induced by 9-cis-RA. Like treatment with low
      calcium medium, these inhibitors did not prevent the 9-cis-RA-induced increase in
      total beta-catenin protein levels, but completely prevented the movement of beta
      catenin to the cell membrane. These results point to a role for beta-catenin and
      serine kinase activity in mediating the action of 9-cis-RA in epithelial
      differentiation.

PMID- 8754751
TI  - The combined action of two thyroidal proteases releases T4 from the dominant
      hormone-forming site of thyroglobulin.
AB  - Thyroid hormones are synthesized within the thyroglobulin (Tg) molecule and must
      be released to reach the circulation and exert their metabolic effect. We have
      previously shown that three lysosomal endopeptidases, cathepsin B, D, and L, are
      active in the early stages of intrathyroidal degradation of Tg but do not
      themselves release free hormone. The current study examines the role of
      exopeptidases as the next step in thyroid hormone release. Human thyroidal
      cathepsin B and two partially purified exopeptidases, dipeptidyl peptidase II (DP
      PII) and lysosomal dipeptidase I (LDPI), were used to digest the 20-kDa N
      terminal peptide of rabbit Tg, which contains the dominant T4 site of Tg at
      residue 5. Cathepsin B acted as an endopeptidase initially, producing small T4
      containing peptides. After more extended digestion, it also acted as an
      exopeptidase, producing the dipeptide T4-Gln, corresponding to residues 5 and 6
      of Tg. Lysosomal dipeptidase I alone had no effect on 20 kDa but acted in
      combination with cathepsin B to release T4 from the T4-Gln dipeptide. Although
      addition of DPPII increased the release of hormone from 125I-Tg by an extract of
      DPPII-deficient lysosomes, it had no apparent effect on the degradation of the 20
      kDa peptide, either alone or in combination with cathepsin B or LDPI. Thus DPPII
      may act in synergy with some other endopeptidase, or alternatively, may play a
      role in the release of hormone from other sites in Tg. We conclude that the N
      terminus of Tg, which contains its major hormonogenic site, is particularly
      susceptible to hydrolysis by the endopeptidase cathepsin B and that cathepsin B
      additionally has an important exopeptidase action that allows it to release a T4
      dipeptide that is then further degraded by LDPI to release free T4.

PMID- 8754752
TI  - Distinct regions of thyroglobulin control the proliferation and suppression of
      thyroid-specific lymphocytes in obese strain chickens.
AB  - The effect of thyroglobulin (Tg)iodination on the proliferation and suppression
      of thyroid-specific lymphocytes was examined in vivo in the obese strain (OS) and
      Cornell strain chicken models of autoimmune thyroiditis. Spleen cells from OS
      chickens were able to transfer disease to Cornell strain recipients. The ability
      to transfer disease was markedly reduced if the donors were raised on an iodine
      depleting regimen. This deficiency was corrected by immunization of donor
      chickens with iodinated Tg. Immunization with low iodine Tg was ineffective.
      Neonatal tolerance induction with either iodinated or low iodine Tg reduced
      thyroiditis in 2-week-old OS chickens. Spleen cells from these tolerized chickens
      transferred to 4-day-old OS chickens were less thyroiditogenic. These results
      indicate that thyroid autoreactive cells are responsive to iodinated Tg, but not
      to low iodine Tg. Both of the Tg preparations, however, can induce tolerance to
      the disease. We conclude that distinct regions of the Tg molecule regulate the
      proliferation and suppression of thyroid-reactive lymphocytes, respectively. Only
      the former is dependent on the iodination of Tg. These results emphasize the
      importance of Tg as a self-antigen and provide one mechanism by which iodine may
      induce autoimmune thyroiditis.

PMID- 8754753
TI  - Agonist and receptor binding properties of adrenocorticotropin peptides using the
      cloned mouse adrenocorticotropin receptor expressed in a stably transfected HeLa
      cell line.
AB  - The cloned mouse ACTH receptor was expressed in stably transfected human HeLa
      cells that lack an endogenous melanocortin receptor. ACTH[1-39] and several N-
      and C-terminally truncated analogues of ACTH were studied for their ability to
      stimulate cAMP generation and to displace bound 125I-ACTH. Only three of the
      peptides tested, ACTH[1-24], ACTH[1-39], and ACTH[1-17] were found to have
      agonist activity with EC50 values of 7.5, 57, and 49 x 10(-12) M respectively.
      Two peptides, ACTH[11-24] and ACTH[7-39], were devoid of agonist activity but had
      substantial competitive antagonist activity with IC50 values of approximately 10(
      9) M. In binding studies, ACTH[1-39] and ACTH[1-24] were able to fully displace
      bound ligand, and Scatchard analysis indicated a dissociation constant (KD) of
      0.84 and 0.94 x 10(-9) M for the two peptides, respectively. ACTH[1-17], ACTH[11
      24], and ACTH[7-39] were only capable of displacing 60-70% of bound ligand. A
      three-site model for the interaction of ACTH and its receptor is proposed on the
      basis of these findings.

PMID- 8754754
TI  - Insulin-like growth factor-binding protein-1 expression in cultured human bone
      cells: regulation by insulin and glucocorticoid.
AB  - Insulin-like growth factors (IGFs) and their specific regulatory binding proteins
      (IGFBPs) are postulated to play a key role in bone metabolism. To date, IGFBP-2
      through -6 have been characterized in bone cell systems. In this study we focused
      on IGFBP-1. Primary cultures of normal human osteoblasts derived from trabecular
      bone (hOB cells) expressed low levels of IGFBP-1 messenger RNA (mRNA), as
      determined by Northern analyses. Treatment of hOB cells with 1 microM cortisol or
      100 nM dexamethasone for 20 h stimulated IGFBP-1 mRNA expression 5-fold and
      increased levels of immunoassayable IGFBP-1 in the conditioned medium 3-fold.
      Estradiol and progesterone had no effect. IGFBP-1 expression was not observed in
      U-2, TE-85, or MG-63 human osteosarcoma cell lines or in normal human
      fibroblasts. Insulin (1-100 nM) potently inhibited both basal and glucocorticoid
      stimulated IGFBP-1 expression in hOB cells. Insulin had little or no effect on
      steady state levels of the other IGFBP mRNA. A monoclonal antibody to the insulin
      receptor blocked insulin binding to insulin receptors and completely prevented
      insulin-induced suppression of IGFBP-1. In summary, we have documented IGFBP-1
      mRNA and protein expression in normal nontransformed human osteoblastic cells.
      This expression was stimulated by glucocorticoids and inhibited by insulin in a
      manner similar to IGFBP-1 regulation in hepatocytes. Insulin acts through insulin
      receptors on hOB cells. We postulate that IGFBP-1 produced by osteoblasts in vivo
      can modulate local actions of IGF on bone formation in response to changes in
      glucocorticoid and insulin concentrations.

PMID- 8754755
TI  - The oxytocin antagonist atosiban prevents androstenedione-induced myometrial
      contractions in the chronically instrumented, pregnant rhesus monkey.
AB  - We tested the hypothesis that increased oxytocin is a necessary mechanism for the
      mediation of androstenedione (delta 4A)-induced myometrial contractions by
      investigating the effects of maternal treatment with the oxytocin antagonist
      atosiban on in vivo delta 4A-induced contractions. In four monkeys (group I),
      maternal estradiol, oxytocin, and myometrial contractions were assessed at
      baseline and after continuous iv delta 4A administration. Similar measurements
      were made in three monkeys (group II) that received the same delta 4A infusion
      regimen, but in addition were treated daily with atosiban. Maternal estradiol and
      oxytocin levels and contractions were also assessed in four additional monkeys
      (controls; group III), in which the delta 4A vehicle, intralipid, was infused iv
      continuously. In group I, delta 4A induced myometrial contractions and increased
      maternal estradiol and oxytocin to term concentrations. No myometrial
      contractions occurred in group II monkeys after combined delta 4A and atosiban
      treatment despite estradiol being elevated to concentrations similar to those
      measured in group I monkeys. Atosiban had no effect on maternal heart rate or
      blood pressure. Maternal estradiol, oxytocin, and number of myometrial
      contractions remained unchanged from baseline values in control monkeys. In
      conclusion, oxytocin is a necessary part of the mechanisms mediating delta 4A
      induced myometrial contractions. delta 4A promotes myometrial contractions via
      similar mechanisms that mediate spontaneous term contractions in pregnant
      monkeys.

PMID- 8754756
TI  - Molecular biological and biochemical characterization of the human type 2
      selenodeiodinase.
AB  - Type 2 deiodinase (D2) is a low K(m) iodothyronine deiodinase that catalyzes the
      removal of a single iodine from the phenolic ring of T4 or rT3. We sequenced and
      subcloned the open reading frame from a partial complementary DNA (cDNA) clone
      (2.1 kilobases) prepared by Genethon (Z44085) from a human infant brain cDNA
      library. The open reading frame encodes a putative 273-amino acid protein of 31
      kDa with greater than 70% similarity to the Rana catesbeiana D2 protein.
      Transient expression of the cDNA produces a low K(m) (5 nM for T4; 8 nM for rT3)
      propylthiouracil- and gold thioglucose-resistant 5'-deiodinase in 293-HEK cells.
      Human D2, like human type 1 (D1) and type 3 (D3) deiodinases, is a selenoenzyme,
      as evidenced by 1) the presence of two in-frame UGA codons (positions 133 and
      266), 2) the synthesis of a 31-kDa 75Selabeled protein in D2 cDNA-transfected
      cells, and 3) the requirement for a 3'-selenocysteine incorporation sequence
      element for its translation. Unlike D1 and D3, we were not able to covalently
      label overexpressed D2 with N-bromoacetyl [125I]T3 or -T4. We found that the
      human D2 messenger RNA is 7-8 kilobases and is expressed in brain, placenta, and,
      surprisingly, cardiac and skeletal muscle. Type 2 deiodinase activity was also
      present in human skeletal muscle. These results indicate that there are unique
      features of D2 that distinguish it from the two other selenodeiodinases. The
      expression of D2 in muscle suggests that it could play a role in peripheral, as
      well as intracellular, T3 production.

PMID- 8754757
TI  - Low level cyclic adenosine 3',5'-monophosphate accumulation analysis of [des
      His1, des- Phe6, Glu9] glucagon-NH2 identifies glucagon antagonists from weak
      partial agonists/antagonists.
AB  - [des-His1, des-Phe6,Glu9]Glucagon-NH2 is a newly designed glucagon antagonist.
      This analog has a binding IC50 of 48 nM (compared to glucagon IC50 of 1.5 nM) and
      demonstrates pure antagonism in an adenylate cyclase assay. Although the number
      of glucagon antagonists has grown rapidly recently, closer examination suggested
      that many of these antagonists retained very low, almost imperceptible levels of
      cAMP accumulation that were sufficient to elicit an in vivo biological response.
      To investigate more carefully this secondary biological signal, we measured cAMP
      accumulation in a revised assay using isolated hepatocytes in the presence of the
      phosphodiesterase (PDE) inhibitor Rolipram. The PDE inhibitors Rolipram and
      isobutyl-1-methylxanthine (IBMX) increased the sensitivity of the cAMP
      accumulation assay from approximately 10-fold for the native hormone to 35-fold
      above basal levels. On the other hand, amrinone, another PDE inhibitor, did not
      affect the cAMP accumulation caused by glucagon. The use of PDE inhibitors
      indicated that three glucagon analogs that had previously been reported to have
      strong antagonist properties in classical adenylate cyclase assays were actually
      weak partial agonists in this new assay system. [N alpha-Trinitrophenyl-His1,
      homo-Arg12]glucagon, [des-amino-His1,D-Phe4,Tyr5, Arg12, Lys17,18,Glu21]glucagon,
      and [des-His1,Glu9]glucagon-NH2 demonstrated 233%, 21%, and 5.5% cAMP
      accumulation relative to the native hormone in the presence of 25 microM
      Rolipram. On the other hand, [des-His1,des-Phe6,Glu9]glucagon-NH2, a newly
      designed glucagon antagonist, did not activate adenylate cyclase in the presence
      of Rolipram up to a maximal physiological concentration of 1 microM, indicating
      that it was a pure antagonist of glucagon-induced adenylate cyclase activity and
      also the first one in this class. This compound and others were tested in a
      glycogen phosphorylase assay. As [des-His1,des- Phe6,Glu9]glucagon-NH2 did not
      activate phosphorylase activity, it was chosen as our candidate for in vivo
      testing in streptozotocin-induced diabetic rats. An initial dose of 0.75 mg/kg
      was found to cause the greatest lowering of blood glucose levels (to 63% of the
      initial levels in 15 min) when the bolus was followed by continuous infusion of
      25 micrograms/kgxmin for 1 h.

PMID- 8754758
TI  - Developmental regulation of corticosteroid-binding globulin biosynthesis in the
      baboon fetus.
AB  - The present study determined the roles of estrogen and cortisol in maternal and
      fetal corticosteroid-binding globulin (CBG) levels and fetal hepatic messenger
      RNA (mRNA) expression in the baboon. Samples of fetal liver, kidney, and brain
      were obtained from untreated control animals at early (day 60; n = 4), mid (day
      100; n = 8), and late (day 165; n = 5) gestation (term = day 184). Maternal and
      umbilical blood samples were collected on day 100 from baboons in which
      betamethasone was administered sc to the mother (n = 6) on days 60-99 of
      gestation and on day 165 from animals (n = 4) in which the fetus was administered
      betamethasone on days 150-164 of gestation. Maternal serum cortisol
      concentrations were similar at mid (43 +/- 2 micrograms/dl) and late (42 +/- 3
      micrograms/dl) gestation and decreased (P < 0.05) at midgestation (1 +/- 1
      micrograms/dl) and term (31 +/- 4 micrograms/dl) after betamethasone treatment.
      Umbilical serum cortisol levels were also reduced (P < 0.05) at both mid (1 +/- 1
      micrograms/dl) and late (14 +/- 5 micrograms/dl) gestation by betamethasone
      treatment. Fetal serum CBG levels in untreated animals were lower (P < 0.05) on
      day 165 (444 +/- 29 pmol/ml) than on day 100 (844 +/- 35 pmol/ml) and increased
      (P < 0.05) at midgestation (1098 +/- 64 pmol/ml), but not at term (551 +/- 24
      pmol/ml), after betamethasone treatment. In contrast, maternal serum CBG levels
      (range, 528-770 pmol/ml) were not altered by gestational age or betamethasone.
      The human CBG complementary DNA hybridized to a single mRNA species of 1.8
      kilobases in baboon fetal liver; however, CBG was not expressed in fetal kidney
      and was detectable in fetal brain and pancreas only by reverse transcription-PCR.
      In untreated baboon fetuses, the mRNA levels of hepatic CBG, expressed as a ratio
      of 18S RNA, progressively decreased (P < 0.05) in early (1.83 +/- 0.17), mid
      (0.97 +/- 0.12), and late (0.51 +/- 0.04) gestation. These results demonstrate
      that fetal hepatic CBG mRNA expression and serum CBG concentrations were elevated
      early in baboon gestation and exhibited a progressive decline during the course
      of advancing pregnancy. We suggest that the increased levels of fetal CBG in the
      early stages of gestation reflect stimulation of hepatic CBG synthesis by
      maternal cortisol, which we previously demonstrated to occur in the fetus as a
      result of preferential 11 beta-hydroxysteroid dehydrogenase-catalyzed
      glucocorticoid reduction across the placenta. The decline in fetal CBG may
      reflect the developmental increase in catabolism of cortisol to bioinactive
      cortisone in target tissues of the fetus such as the liver.

PMID- 8754759
TI  - Thyrotropin (TSH) receptor antibodies (TSHrAb) can inhibit TSH-mediated cyclic
      adenosine 3',5'- monophosphate production in thyroid cells by either blocking TSH
      binding or affecting a step subsequent to TSH binding.
AB  - In the present study, rabbit antibodies that possess thyroid stimulation-blocking
      activity were used to investigate potential mechanisms by which TSH receptor
      antibodies can inhibit thyroid cell function. The antibodies were produced
      against two synthetic peptides corresponding to amino acids 357-372 (p357) and
      367-386 (p367) of the human TSHr (hTSHr). By enzyme-linked immunosorbent assay,
      both antisera (alpha 357 and alpha 367) had high titers ( > 1:100,000) of IgG
      against their respective peptides and recombinant extracellular TSHr protein
      (ETSHr); alpha 357 had a low IgG titer to p367 (1:800), and alpha 367 had a low
      IgG titer to p357 ( < 1:200). Based on competitive inhibition studies, alpha 357
      and alpha 367 displayed similar relative binding affinities for their respective
      peptides and for recombinant ETSHr. When tested by commercial RRA, alpha 357 did
      not block (TSH binding inhibition index, -3.7%), whereas alpha 367 blocked TSH
      binding to TSHr (TSH binding inhibition index, 53.9%). The blocking effect of
      alpha 367 could be reversed by incubating the antiserum with p367 before assay.
      When applied alone to FRTL-5 cells, IgG from alpha 357 inhibited [compared to
      normal rabbit IgG (NRI); P < 0.01] based cAMP production by the cells, whereas
      IgG from alpha 367 did not. IgG from both alpha 357 and alpha 367, however, were
      able to inhibit (P < 0.001) TSH-mediated cAMP production by FRTL-5 cells [bovine
      (b) TSH, 2.5 x 10(-10) M; cAMP (mean +/- SD; picomoles per ml): NRI, 62.5 +/-
      6.1; alpha 357, 12.2 +/- 2.4; alpha 367, 36.2 +/- 3.5]. Alpha 357 continued to
      inhibit (P < 0.05) cAMP production by FRTL-5 cells in 10(-8) M bTSH, whereas
      alpha 367 no longer inhibited cAMP production at bTSH concentrations above 5 x
      10(-10) M. Compared to NRI, both alpha 357 and alpha 367 were also able to
      inhibit (P < 0.001) Graves' IgG-mediated cAMP production by FRTL-5 cells. When
      IgG were tested on FRTL-5 cells in the presence of 10(-7) M forskolin, only alpha
      357 inhibited (P < 0.001) cAMP production (NRI, 75.1 +/- 4.8; alpha 357, 52.3 +/-
      4.5; alpha 367, 77.2 +/- 1.4). To determine whether the inhibitory effect of
      alpha 357 on forskolin-mediated stimulation was thyroid cell dependent, IgG were
      tested on Chinese hamster ovary (CHO) cells transfected with the complementary
      DNA of the hTSHr (CHO-R). Again, alpha 357 inhibited (P < 0.005) cAMP production
      mediated by forskolin (at 10(-7) M; NRI, 68.7 +/- 4.4; alpha 357, 36.8 +/- 5.7;
      alpha 367, 64.6 +/- 8.5). alpha 357 did not inhibit forskolin-mediated cAMP
      production by untransfected CHO cells (CHO-N), indicating that the inhibitory
      effect of alpha 357 on forskolin stimulation was TSHr dependent. In addition,
      alpha 357 inhibited (P < 0.01) basal cAMP production by CHO-R cells, but not by
      CHO-N cells. alpha 367 had no effect on the basal cAMP production in either CHO-R
      or CHO-N cells. Neither alpha 357 nor alpha 367 inhibited cholera toxin-mediated
      cAMP production in FRTL-5 cells. In all relevant bioassays, the inhibitory
      effects of alpha 357 and alpha 367 could be reversed by preincubating the IgG
      with the respective peptides. From these data, we conclude that 1) alpha 367
      binds to the ETSHr and blocks TSH-mediated cAMP production by inhibiting TSH from
      binding to its receptor; 2) alpha 357 binds to the TSHr and, without blocking TSH
      binding, inhibits TSH-mediated cAMP production at a step(s) subsequent to ligand
      binding that affects adenylate cyclase activity; and 3) forskolin-mediated cAMP
      production by thyroid cells can be inhibited by IgG that bind directly to the
      TSHr.

PMID- 8754760
TI  - Differential growth regulation by all-trans retinoic acid is determined by
      protein kinase C alpha in human pancreatic carcinoma cells.
AB  - We have investigated the role of protein kinase C (PKC) isoenzymes in the
      differential growth regulation of human pancreatic carcinoma cell lines by all
      trans retinoic acid (RA). RA treatment results in dose-dependent stimulation of
      anchorage-independent growth in AsPc1 cells and growth inhibition in Capan 2
      cells. Both cell lines express an identical pattern of nuclear RA and retinoid X
      receptors as determined by RT-PCR. Western blotting using monospecific antibodies
      revealed that both cell lines express PKC isoenzymes alpha and zeta, whereas
      beta, gamma, delta, and epsilon were not detected. Incubation with RA in the
      growth-stimulated AsPc1 cell line resulted in induction of PKC alpha expression,
      whereas PKC alpha expression was decreased by RA in the growth-inhibited Capan 2
      cell line. In contrast, PKC zeta expression was not affected by RA in either cell
      line. Incubation of AsPc1 cells with the phorbol ester 12-O-tetradecanoyl phorbol
      13-acetate resulted in a time- and dose-dependent selective down-regulation of
      PKC alpha but not zeta. The dose-dependent decrease of intracellular PKC alpha
      concentration correlated well with the anchorage-independent growth rate of AsPc1
      cells. Furthermore, selective down-regulation of PKC alpha blocks subsequent
      growth stimulation by RA in AsPc1 cells. When PKC alpha concentration was
      decreased by stably transfecting AsPc1 cells with a PKC alpha complementary DNA
      antisense construct, RA-stimulated growth could also be partially blocked. These
      data, therefore, suggest that differential regulation of PKC alpha expression
      plays a central role in determining the bidirectional effects of RA on growth in
      pancreatic carcinoma cells.

PMID- 8754762
TI  - Cell-to-cell communication in the anterior pituitary: evidence for gap junction
      mediated exchanges between endocrine cells and folliculostellate cells.
AB  - The ability of rat anterior pituitary cells to communicate through gap junctions
      (GJ) was studied using a fluorescent molecule, Lucifer Yellow (LY), which freely
      passes through GJ channels. The probe was introduced into the cell cytoplasm by
      using either the cut-end loading method on intact tissue, or cell microinjection
      on cultured cells. The identification of communicating cells was performed by
      immunofluorescence labeling of specific hormones in endocrine cells and of S100
      protein in folliculostellate (FS) cells. Rat anterior pituitary cells in their
      physiological organization, i.e. in the intact tissue, exhibited a high level of
      coupling through GJ. LY-labeled cells were found up to 300-microns apart from its
      site of introduction. The communicating cells were primarily PRL cells, GH cells,
      and FS cells. Only a few LH, TSH, and ACTH cells were labeled with LY. Anterior
      pituitary cells, isolated from the rat tissue by mild protease treatment and
      cultured for 3 days, reestablished functional GJ as demonstrated by
      microinjection of LY into individual cells. By immunolabeling of specific
      hormones and/or S100 protein, we found a GJ coupling between FS cells, and
      between FS cells and endocrine cells, including PRL cells. The communication
      between FS cells was by far the most frequent. In conclusion, we demonstrate the
      presence of functional GJ between anterior pituitary cells of the same type and
      between anterior pituitary cells having distinct differentiated functions.

PMID- 8754761
TI  - Distinct mechanisms regulate induction of messenger ribonucleic acid for
      prostaglandin (PG) G/H synthase-2, PGE (EP3) receptor, and PGF2 alpha receptor in
      bovine preovulatory follicles.
AB  - We have evaluated the in vivo and in vitro regulation and temporal expression of
      messenger RNA (mRNA) for prostaglandin (PG) G/H synthase-2 (PGHS-2) and two
      specific PG receptors, PGF2alpha receptor (FP receptor) and PGE receptor EP3
      subtype (EP3 receptor), in bovine preovulatory follicular cells and luteal cells.
      An in vivo study showed that PGHS-2 mRNA was not detected in granulosa cells and
      was highly but transiently induced by the LH surge before ovulation. FP and EP3
      receptor mRNAs were present at extremely low concentrations in granulosa or
      thecal cells and did not increase before ovulation. Messenger RNA for FP receptor
      increased more than 500- and 2500-fold at 24 and 48 h after ovulation,
      respectively, and these high amounts were maintained at midluteal phase. On the
      other hand, mRNA for EP3 receptor remained low with FP receptor mRNA 1000-fold
      greater than EP3 receptor mRNA in the corpus luteum. In vitro culture of bovine
      granulosa cells using hCG, forskolin, and phorbol didecanoate demonstrated that
      induction of FP receptor mRNA was mediated through protein kinase (PK) A. In
      contrast, EP3 receptor mRNA was stimulated through PKC. PGHS-2 was acutely ( < 12
      h) increased by PKA, and to a lesser extent by PKC. Temporal expression of FP
      receptor mRNA is not consistent with the involvement of FP receptor in ovulation
      and suggests that PKA stimulates PGHS-2 and FP receptor mRNA by distinct
      mechanisms.

PMID- 8754763
TI  - Elevated levels of growth hormone increase bone mineral content in normal young
      mice, but not in ovariectomized mice.
AB  - Both estrogens and GH are necessary for normal bone remodeling. This study
      investigates the effect of elevated GH levels on the amount and density of bone
      in young female mice and its dependence on intact ovarian function.
      Metallothionein promoter-GH-transgenic mice were either sham operated or
      ovariectomized at 25-29 days of age, and the bone measurements were made at about
      90 days of age. A 6-mm high cylinder containing only cortical bone was cut from
      the right tibia, and lumbar vertebrae 6 was measured as a bone with predominantly
      cancellous bone. The amounts of tibial and vertebral bone, measured by dry
      weight, mineral weight, organic weight, bone mineral content (measured by dual
      energy x-ray analysis), and volume, were increased in GH-transgenic animals
      compared to those in normal littermates. This stimulatory effect of elevated GH
      levels was not seen in ovariectomized mice. The real density of the tibial bone
      were slightly decreased in GH-transgenic animals compared to normal littermates.
      In conclusion, elevated levels of GH increase the amounts of vertebral
      (predominantly cancellous) bone and tibial (cortical) bone in young mice. Intact
      ovaries are a prerequisite for the stimulatory effect of elevated levels of GH.
      The fact that ovariectomy decreases the stimulatory effect of elevated GH levels
      suggests that the effect of elevated GH levels in bone is dependent upon the
      presence of basic sex steroid secretion.

PMID- 8754764
TI  - Epiandrosterone and dehydroepiandrosterone affect glucose oxidation and
      interleukin-1 beta effects in pancreatic islets.
AB  - Isolated rat islets or RINm5F insulinoma cells treated with interleukin-1 beta
      (IL-1 beta) for 18 h show reduced glucose-sensitive insulin release and increased
      nitrite formation as a result of nitric oxide synthase induction. Although a
      phosphodiesterase inhibitor, isobutylmethylxanthine, potentiated insulin release
      in response to glucose stimulation, the secretory response was not restored to
      normal in IL-1 beta-treated islets. Islets that were cultured for 18 h in the
      presence of IL-1 beta and epiandrosterone (EA) or dehydroepiandrosterone (DHEA)
      and then washed responded with a concentration-dependent reversal of the effects
      of IL-1 beta on insulin release in the presence of a glucose or glucose plus
      isobutylmethylxanthine stimulus. In contrast, when EA and DHEA were not washed
      from the islets before determination of insulin release, the presence of EA or
      DHEA inhibited insulin release in both freshly isolated and cultured islets.
      Nitrite formation in islets and RINm5F cells in response to IL-1 beta was also
      significantly reduced during culture with EA or DHEA, although nitrite levels
      were still elevated above control values. Neither steroid affected cell growth or
      DNA or protein content. Pyrrolidine dithiocarbamate also reduced IL-1 beta
      induced nitrite formation. EA and DHEA inhibited [U-14C]glucose oxidation in
      islets and RINm5F cells. Comparison of [1-14C]glucose and [6-14C]glucose
      oxidation in islets and RINm5F cells when EA was present during culture and
      metabolic determination indicated that EA inhibited glycolysis and the pentose
      shunt contribution to glucose utilization. Neither IL-1 beta in islets nor DHEA
      in RINm5F cells inhibited pentose shunt activity, although total glucose
      oxidation and utilization were inhibited. The effects of DHEA and EA on glucose
      oxidation were rapidly reversible. EA and DHEA reduced glucose-6-phosphate
      dehydrogenase activity only when added directly to tissue homogenates. Thus, EA
      and DHEA antagonize the effects of IL-1 beta on beta-cells. Inhibition of glucose
      metabolism and pentose shunt activity may protect the cells from nitric oxide
      synthase activation and related toxicities.

PMID- 8754765
TI  - Beta-endorphin enhances Concanavalin-A-stimulated calcium mobilization by murine
      splenic T cells.
AB  - Intracellular calcium mobilization is an important early event involved in T cell
      activation. The endogenous opioid peptide beta-endorphin is known to modulate
      immune functions that depend on T cell activation, therefore its effect on
      intracellular calcium mobilization was investigated. The intracellular calcium
      concentration ([Ca2+]i) of T cell-enriched splenocytes was measured by flow
      cytofluorometric analysis using the calcium-sensitive dye, Fluo-3. By gating on
      the T cell marker, Thy-1, a 95%-pure population of T cells was identified for
      study. Cells preincubated with beta-endorphin showed significantly enhanced
      [Ca2+]i responses to the mitogen, Concanavalin A (Con A). This was detectable
      with concentrations of beta-endorphin as low as 10(-13) M; maximal enhancement
      required 10(-10) to 10(-9) M doses. The efficacy of beta-endorphin was dependent
      on the duration of pretreatment. beta-Endorphin amplified the Con A-induced
      increase in [Ca2+]i by reducing the lag time for the response to Con A and by
      increasing the mean [Ca2+]i of the cells. N-Ac-beta-endorphin, which shows
      minimal potency at neuronal opiate receptors, was unable to substitute for beta
      endorphin. Naltrindole, a highly selective delta opiate receptor antagonist,
      inhibited the action of beta-endorphin, whereas a selective mu opiate receptor
      antagonist was ineffective. Although less potent than beta-endorphin, the delta
      opiate receptor agonist D-Ala2-D-Leu5-enkephalin also significantly enhanced
      [Ca2+]i responses. In summary, concentrations of beta-endorphin, within the
      physiological range found in the systemic circulation, modulate the increase in T
      cell [Ca2+]i induced by Con A. Both the efficacy of D-Ala2-D-Leu5-enkephalin
      alone and the antagonism of beta-endorphin by naltrindole suggest that a delta
      type opiate receptor may mediate these effects.

PMID- 8754766
TI  - Adrenocorticotropin secretion by fetal sheep anterior and intermediate lobe
      pituitary cells in vitro: effects of gestation and adrenalectomy.
AB  - Immunoreactive (ir) ACTH is present in the fetal sheep intermediate lobe (IL) as
      well as the anterior pituitary (AP). It is not clear whether fetal IL cells can
      secrete irACTH and if gestational age and glucocorticoids influence the secretion
      of ACTH from these tissues in a similar fashion. Therefore, we examined the
      control of irACTH secretion by IL cells, whether the responsiveness of AP and IL
      cells to arginine vasopressin (AVP) and CRH changes during gestation, and whether
      withdrawal of adrenal steroids by adrenalectomy influences AP and IL responses.
      Cultured pituitary cells were studied from intact fetuses at an immature (n = 5;
      108 +/- 5 days) and a mature (n = 8; 139 +/- 0 days) stage, from mature fetuses 3
      weeks after bilateral adrenalectomy (n = 6), and from neonatal lambs within 16 h
      of birth (n = 6). Secretion of irACTH was determined by RIA of incubation medium
      obtained during 3-h exposure of cells to vehicle, AVP, CRH, or both. In all
      cases, IL cells secreted measurable irACTH. The IL cells of immature fetuses
      responded to CRH (133 +/- 8% increase over basal secretion), AVP (52 +/- 6%), and
      CRH plus AVP (244 +/- 8%). In contrast, IL cells from mature fetuses responded
      only to CRH (160 +/- 20%) or CRH plus AVP (259 +/- 44%), as did cells from mature
      adrenalectomized fetuses (CRH, 356 +/- 70%; CRH plus AVP, 627 +/- 100%).
      Secretion from neonatal IL cells was not significantly increased above basal
      rates by CRH and/or AVP. The AP cells from immature fetuses responded
      significantly to CRH (406 +/- 16%), AVP (114 +/- 8%), and CRH plus AVP (559 +/-
      38%), whereas cells from mature fetuses responded only to AVP (249 +/- 40%) or to
      CRH plus AVP (570 +/- 146%). In AP cells from mature adrenalectomized fetuses,
      the response pattern resembled that of immature intact fetal sheep (CRH, 429 +/-
      76%; AVP, 146 +/- 15%; CRH plus AVP, 541 +/- 94%). Neonatal AP cells responded to
      CRH (196 +/- 25%), AVP (442 +/- 71%), and CRH plus AVP (646 +/- 93%). Further
      characterization of IL cells (n = 6 fetal and 2 neonatal) indicated that they
      were inhibited by dopamine (basal ACTH secretion decreased by 25 +/- 4%; ACTH
      secretory response to CRH decreased by 32 +/- 10%). These results show that fetal
      neurointermediate lobe cells secrete irACTH under basal and stimulated
      conditions. Moreover, the pattern of response of AP and neurointermediate lobe
      cells to secretagogues is influenced by gestational age and, possibly, cortisol.

PMID- 8754767
TI  - Differential effects and glucocorticoid potentiation of bone morphogenetic
      protein action during rat osteoblast differentiation in vitro.
AB  - Bone morphogenetic proteins (BMPs) induce cartilage and bone differentiation in
      vivo and promote osteoblast differentiation from calvarial and marrow stromal
      cell preparations. Functional differences between BMP-2, -4, and -6 are not well
      understood. Recent investigations find that these three closely related
      osteoinductive proteins may exert different effects in primary rat calvarial cell
      cultures, suggesting the possibility of unique functions in vivo. In this study,
      we use a fetal rat secondary calvarial cell culture system to examine the
      differential effects of BMP-2, -4, and -6 on early osteoblast differentiation.
      These cells do not spontaneously differentiate into osteoblasts, as do cells in
      primary calvarial cultures, but rather require exposure to a differentiation
      initiator such as glucocorticoid or BMP. We determined that BMP-6 is a 2- to 2.5
      fold more potent inducer of osteoblast differentiation than BMP-2 or -4. BMP-6
      induced the formation of more and larger bone nodules as well as increased
      osteocalcin secretion. The effects of all three of these BMPs were potentiated up
      to 10-fold by cotreatment or pretreatment with the glucocorticoid triamcinolone
      (Trm). The Trm effects were synergistic with those of BMP-2 or -4, suggesting
      that this glucocorticoid may increase the cell responsiveness to these BMPs.
      Finally, BMP-6 did not require either cotreatment or pretreatment with Trm to
      achieve greater amounts of osteoblast differentiation than seen with BMP-2 or BMP
      4 treatment, suggesting that BMP-6 may act at an earlier stage of cell
      differentiation.

PMID- 8754768
TI  - Insulin induces a change in Rab5 subcellular localization in adipocytes
      independently of phosphatidylinositol 3-kinase activation.
AB  - We investigated whether Rab5, a small guanosine triphosphatase that regulates
      early endocytic transport in different cell types is involved in the insulin
      regulated endocytic pathways in adipocytes. Rab5 was detected in freshly isolated
      adipocytes and 3T3-L1 adipocytes, but its expression level was not markedly
      increased with adipocyte differentiation. After subcellular fractionation of
      adipocytes incubated in the absence of insulin, Rab5 was found to be abundant in
      plasma membrane and cytosol, but was also present in high and low density
      microsomes. This subcellular distribution was compatible with a role in early
      endocytosis. When cells were incubated with insulin, the concentration of Rab5
      decreased by about 50% in the internal compartments. In contrast to Rab4, which
      also leaves the low density microsomes in response to insulin, Rab5 was not found
      in Glut4-containing vesicles purified by immunoadsorption on antibodies to Glut4.
      When adipocytes were treated with wortmannin, an inhibitor of
      phosphatidylinositol 3-kinase, the effect of insulin on Rab5 movement was not
      affected, whereas the insulin-induced movements of Rab4 and Glut4 were abolished.
      In parallel, wortmannin inhibited the increase in horseradish peroxidase uptake
      induced by insulin, an index of fluid phase endocytosis, but did not prevent the
      endocytosis of the glucose transporters. As a whole, our results suggest that
      Rab5 is not involved in insulin-stimulated Glut4 exocytosis. These results are
      compatible with the postulated role of Rab5 in the endocytotic pathway, at a step
      that does not require phosphatidyl-inositol 3-kinase activation.

PMID- 8754769
TI  - Insulin receptor-induced phosphorylation of cellular and synthetic substrates is
      regulated by the receptor beta-subunit C-terminus.
AB  - The transmembrane beta-subunits of the insulin receptor possess hormone-sensitive
      tyrosine kinase activity. To study the role of the C-terminus domain, a rabbit
      antipeptide antibody directed to the 1294-1317 domain was produced. The
      antipeptide antibody inhibited the receptor-induced phosphorylation of poly (Glu,
      Tyr) and synthetic peptides corresponding to the receptor autophosphorylation
      sites. In contrast, the same antibody did not inhibit receptor
      autophosphorylation. The kinetic parameters of the poly(Glu, Tyr) phosphorylation
      reaction indicated that the antibody interfered with the receptor enzymatic site.
      Concerning the insulin receptor cellular substrates, the anti-(1294-1317)
      antibody inhibited Src homology/collagen and IRS-1 phosphorylation. The extent of
      inhibition was 52% for Src homology/collagen phosphorylation and 30% for IRS-1
      phosphorylation. From our data, we conclude that a similar regulation of insulin
      receptor-induced phosphorylation of artificial and cellular insulin receptor
      substrates can be generated at the level of the receptor beta-subunit C-terminus.

PMID- 8754770
TI  - Pituitary adenylate cyclase-activating polypeptide acts within the medial basal
      hypothalamus to inhibit prolactin and luteinizing hormone secretion.
AB  - In this study, we investigated the hypothalamic regulatory role of pituitary
      adenylate cyclase-activating polypeptide (PACAP) in the control of LH and PRL
      secretion. Overiectomized ewes were surgically prepared with bilateral guide
      tubes directed at the preoptic area (POA) or medial basal hypothalamus (MBH).
      After recovery from surgery, PACAP38 (0.1 nmol in 2.5 microliters over 1 h) or
      vehicle was bilaterally infused into each site in separate trials. Infusion of
      PACAP38 into the POA had no effect on either LH or PRL secretion. However,
      infusion of the peptide into the MBH suppressed PRL secretion during the 3-h
      postinfusion period; the responding animals (n = 9) had injectors located in the
      arcuate nucleus. In the three nonresponding animals, both injectors were outside
      the arcuate nucleus. Mean LH concentration, LH pulse frequency, and pulse
      amplitude were also significantly suppressed, with LH pulsatility declining in
      seven of eight animals during infusion of the peptide in the MBH. These results
      suggest that PACAP acts in the arcuate nucleus region of the MBH, and not the
      rostral POA, to inhibit both LH and PRL secretion.

PMID- 8754771
TI  - Chronic administration of the luteinizing hormone-releasing hormone (LHRH)
      antagonist cetrorelix decreases gonadotrope responsiveness and pituitary LHRH
      receptor messenger ribonucleic acid levels in rats.
AB  - Continuous exposure to LHRH or its agonistic analogs results in a reduction of
      LHRH receptor sites and messenger RNA (mRNA) transcripts as well as in
      desensitization of the pituitary gonadotropes. To determine, whether LHRH
      antagonists might be similar in this respect to the agonists, we treated male
      rats for 4 weeks with daily sc injections of LHRH antagonist [Ac-D
      Nal2,Phe(4Cl)2,D-Pal(3)3, D-Cit6,D-Ala10]LHRH (Cetrorelix acetate) or LHRH
      agonist, [D-Trp6]LHRH, in doses of 100 micrograms/animal-day. Another group of
      rats received a single im injection of 4.5 mg Cetrorelix pamoate depot, a
      sustained delivery formulation of the LHRH antagonist. An iv stimulation test
      with LHRH (200 ng/rat) was performed after 4 weeks of treatment. The rats were
      killed, and pituitary LHRH receptor characteristics were measured by RRA. To
      examine the effect of LHRH antagonist treatment on the expression of the
      pituitary LHRH receptor gene, some of the rats injected with Cetrorelix pamoate
      depot were killed after 2 weeks, and levels of LHRH receptor mRNA were determined
      by Northern blot and dot blot hybridization to a 32P-labeled rat complementary
      DNA probe. Our data show that LHRH-stimulated LH secretion at 30 min was
      suppressed by approximately 33% (P < 0.01) in rats pretreated with [D-Trp6]LHRH
      compared to that in animals injected with LHRH alone. Pretreatment of the rats
      with the LHRH antagonist suppressed the LH response to LHRH more markedly, the LH
      levels at 30 min were decreased by 89.8% and 96% in groups treated with
      Cetrorelix acetate and Cetrorelix pamoate depot, respectively. The testosterone
      response was virtually abolished in groups receiving Cetrorelix. The
      concentration of pituitary receptors for LHRH fell by 69% in the [D-Trp6]LHRH
      group, whereas the reductions in the Cetrorelix acetate group and in the group
      that received Cetrorelix pamoate depot were 77% and 82%, respectively. Treatment
      with Cetrorelix pamoate depot led to a 75-80% decrease in the levels of 5.0- and
      4.5-kilobase forms of LHRH receptor mRNA compared to those in the control group.
      Dot blot analysis also showed 83% reduction in the mRNA for LHRH receptor. In
      conclusion, these data demonstrate that prolonged administration of LHRH
      antagonists such as Cetrorelix causes an impairment of gonadotropin secretion and
      a marked decrease in the levels of LHRH receptors as well as in the expression of
      the LHRH receptor gene. Thus, the down-regulation of pituitary LHRH receptors
      produced by LHRH antagonists appears to be similar to that resulting from the
      agonists.

PMID- 8754772
TI  - Transcriptional repression of the ovine follicle-stimulating hormone-beta gene by
      17 beta-estradiol.
AB  - Direct transcriptional inhibition of the gene that encodes ovine FSH beta-subunit
      (oFSH beta) by 17 beta-estradiol (E2) has been previously demonstrated by our
      laboratory. To determine which cis-acting elements in the 5'-flanking region of
      this gene may be involved in E2 regulation, DNA constructs containing deletions
      of the 5'-end of the oFSH beta gene were fused to a luciferase reporter and
      tested in transient transfection assays. These oFSH beta-luciferase constructs
      and the human E2 receptor expression vector (HEO) were transfected into primary
      cultures of ovine pituitary cells and subsequently tested with E2. Expression of
      the largest oFSH beta-luciferase construct (-4741 to +759 of oFSH beta) was
      inhibited 50% by 20 nM E2. Repression was dependent upon cotransfection of
      estrogen receptor (HEO) and was E2 dose dependent, with an apparent ED50 similar
      to that of the positive control consensus estrogen-responsive element construct,
      ERETk-LUC (ED50 = 50 pM). Deletion studies indicated that sequences between- 105
      and -84 bp are necessary for this repression. In addition, a synthetic nucleotide
      containing oFSH beta sequences from - 105 to -72 could direct E2-dependent
      repression of a heterologous thymidine kinase promoter that drives luciferase
      expression. Additional experiments showed that no tissue-specific elements were
      required for either basal expression or E2-directed transcriptional repression.
      Although there are no consensus DNA response elements for the estrogen receptor
      between -105 and +759 of the oFSH beta gene, cotransfection of a mutant E2
      receptor lacking the DNA-binding domain (HE-11) failed to mediate E2-dependent
      inhibition. Gel retardation studies, using the oligonucleotide-containing oFSH
      beta sequences from -105 to -72, indicated no evidence of direct binding of the
      estrogen receptor to DNA from -105 to -72. The studies presented here indicate
      that transcriptional repression of the oFSH beta gene by E2 may be directed in
      vivo by 5'-flanking sequences between -105 and -72 of the oFSH beta gene.
      Furthermore, the data suggest that inhibition is mediated via E2 receptor-protein
      interactions with basal transcription factors that may bind to the -105/-72 DNA
      directly.

PMID- 8754773
TI  - Depletion and repopulation of Leydig cells in the testes of aging brown Norway
      rats.
AB  - The capacity of Brown Norway rat Leydig cells to produce testosterone has been
      shown to decrease with aging. Our objectives herein were to determine 1) whether
      ethane dimethanesulfonate (EDS) administration would eliminate the hypofunctional
      Leydig cells of the aged Brown Norway rat testis; 2) if so, whether a new
      generation of Leydig cells subsequently would appear; and 3) if so, whether the
      steroidogenic capacity of the new Leydig cells would be at the relatively low
      level of the cells they replaced or at the high level of young adult Leydig
      cells. Young (3-month-old) and aged (18-month-old) rats received an injection of
      EDS (8.5 mg/100 g BW). One, 5, and 10 weeks thereafter, the serum testosterone
      concentration and the capacity of the testes and of isolated Leydig cells to
      produce testosterone were determined. One week after EDS treatment, Leydig cells
      were not seen in the testes of young or aged rats, and the serum testosterone
      concentration and testicular testosterone production were reduced to undetectable
      levels. Five weeks after EDS treatment, serum testosterone levels at both ages
      were restored to those in age-matched controls, and the capacity of the testes to
      produce testosterone was restored partially (young rats) or completely (aged
      rats). By 10 weeks after EDS treatment, the serum testosterone concentration in
      young rats and the ability of their testes to produce testosterone were at the
      levels of age-matched controls. In aged rats, however, serum testosterone and
      testicular testosterone production were at levels that significantly exceeded
      those of aged-matched controls and, indeed, were not significantly different from
      those of young control or EDS-treated rats. Consistent with this, the ability of
      Leydig cells isolated from the testes of young rats and that of cells from aged
      rats to produce testosterone 10 weeks after the rats were treated with EDS were
      equivalent. The enhanced ability of the Leydig cells restored to the aged testes
      to produce testosterone was not a consequence of exposure to increased levels of
      LH. Thus, although situated in an aged testis and in the environment of an aged
      hypothalamic-pituitary axis, the steroidogenic function of the Leydig cells
      restored to aged rat testes was equivalent to that of young rat Leydig cells.

PMID- 8754774
TI  - Differential regulation of luteinizing hormone release by gamma-aminobutyric acid
      receptor subtypes in the arcuate-ventromedial region of the castrated ram.
AB  - We investigated the effects on LH secretion of infusing gamma-aminobutyric acid
      (GABA) agonists muscimol and baclofen (GABAA and GABAB receptor agonists,
      respectively) into either the medial preoptic area (mPOA) or the arcuate
      ventromedial region (ARC-VMR) of the hypothalamus of castrated rams during the
      nonbreeding season. Bilateral microdialysis of artificial cerebrospinal fluid for
      4 h followed by treatment with artificial cerebrospinal fluid, baclofen (1 mM),
      or muscimol (1 mM in the ARC-VMR, 250 microM in the mPOA) for 4 h was carried out
      on three separate occasions in random order. Simultaneously, jugular venous blood
      was collected at 10-min intervals, and plasma later was assayed for LH. The
      estimated dose of baclofen delivered to each unilateral microdialysis site was
      7.9 micrograms; for muscimol, it was 1.1 micrograms for the mPOA and 4.5
      micrograms for the ARC-VMR. In the mPOA, baclofen had no detectable effect,
      whereas muscimol had a delayed suppressive effect on mean LH (P < 0.01). In the
      ARC-VMR muscimol rapidly reduced mean LH (P < 0.01). In contrast, baclofen
      increased mean LH (P = 0.01) and LH pulse amplitude (P = 0.05) without altering
      the LH interpulse interval (P > 0.10). These results support the involvement of
      GABAA receptors in the mPOA in regulating LH secretory patterns. More
      importantly, both GABAA and GABA(B) receptors in the ARC-VMR appear to
      differentially modulate LH and, presumably, GnRH release. Whether GABA acts
      directly on the GnRH neuron or indirectly through other neural systems remains to
      be determined.

PMID- 8754775
TI  - Octapeptide somatostatin analog SMS 201-995 induces translocation of
      intracellular PTP1C to membranes in MCF-7 human breast adenocarcinoma cells.
AB  - Somatostatin (SST) analogs exert direct antiproliferative actions in pancreatic,
      pituitary, and mammary tumor cells in vitro. SST receptor (SSTR)-mediated
      induction of membrane-associated protein tyrosine phosphatase (PTP) activity has
      been implicated in its anti-proliferative signaling by virtue of its ability to
      dephosphorylate and inactivate growth factor receptor kinases. Recently, a PTP
      containing Src homology 2 domain, identified as PTP1C/SHPTP1/SHP/HCP, was found
      to be associated with SSTR in rat pancreatic acinar cell membranes. In the
      present study we investigated the antiproliferative action of the octapeptide SST
      analog SMS 201-995 (OCT) and its effect on PTP activity in MCF-7 human breast
      adenocarcinoma cells. We report here that OCT does not directly stimulate
      membrane-associated PTP activity, but induces translocation of intracellular PTP
      to the membrane in MCF-7 cells preincubated with the peptide in a time- and
      concentration-dependent manner. We demonstrate that this is due at least in part
      to OCT-induced recruitment of cytosolic PTP1C. OCT-induced recruitment of PTP1C
      to the cell surface as well as its ability to inhibit the growth of MCF-7 cells
      was G protein dependent and inhibited by orthovanadate. These findings suggest
      that translocation of cytosolic PTP1C by SST analogs to the cell surface is an
      early event in its antiproliferative signaling in tumor cells.

PMID- 8754776
TI  - Structure, characterization, and expression of the gene encoding the mouse Mel1a
      melatonin receptor.
AB  - Recently, a distinct family of G protein-coupled receptors has been cloned that
      mediates the biological effects of melatonin. Of two sub-types cloned from
      mammals (Mel1a and Mel1b), the Mel1a receptor appears to mediate the circadian
      and reproductive effects of the hormone. We now report the cloning,
      characterization, and expression of the gene encoding the Mel1a receptor in mice.
      The receptor gene is composed of two exons, separated by an intron of greater
      than 13 kilobases. Exon 1 encodes the entire 5'-untranslated region and the
      coding region through the first cytoplasmic loop. Exon 2 encodes the rest of the
      coding region and the entire 3'-untranslated region. 5'-Rapid amplification of
      complementary DNA ends and ribonuclease protection analyses show that the major
      transcription start site is 103 nucleotides upstream of the translation start
      codon. Sequence analysis of 1.1 kilobases of the 5'-flanking region reveals that
      it does not contain TATA or CAAT boxes. The 5'-flanking region drives luciferase
      expression 114-fold over basal levels in a murine retinal cell line that
      endogenously expresses the Mel1a receptor. The mouse receptor binds 2
      [125]iodomelatonin with high affinity (K(d) = 55.6 pM) when expressed transiently
      in COS-7 cells. In situ hybridization studies establish that Mel1a receptor
      messenger RNA is expressed in the hypothalamic suprachiasmatic nuclei and
      hypophyseal pars tuberalis, presumed sites of the circadian and some of
      reproductive actions of melatonin, respectively. These results provide
      information on Mel1a receptor gene structure essential for designing transgenic
      and gene knock-out studies and analyzing the transcriptional regulation of
      receptor gene expression.

PMID- 8754777
TI  - Interactions among receptors, thyroid hormone response elements, and ligands in
      the regulation of the rat uncoupling protein gene expression by thyroid hormone.
AB  - Uncoupling protein (UCP) is essential to the thermogenic function of brown
      adipose tissue (BAT). Thyroid hormone stimulates the rat UCP gene through two
      thyroid hormone response elements (TRE) located upstream of -2,300 and separated
      by 27 bp. They are an everted repeat (upstream TRE or upTRE) and a direct repeat
      (down-stream TRE or dnTRE). The goal of the present studies was to investigate
      whether these TREs interact and how such an interaction could contribute to
      explain the UCP responsiveness to T3 in vivo. We therefore aimed to define: the
      heterodimeric partner of the T3 receptor (T3R); the role of T3 in the receptor
      receptor and receptors-DNA interactions; how such in vitro interactions relate to
      the enhancer function of TREs; and how the two TREs interact. Studies included
      electrophoretic mobility shift assays, utilizing T3R and retinoid X receptors
      (RXR); DNA footprinting; and transient transfections of HIB-1B cells, a BAT
      derived cell line. As in many previously described TREs, the partner of the T3R
      is RXR. The unliganded T3Rs bind to the TREs as homodimers, which act as
      repressors of transcription. T3 reduces the binding of T3R homodimers, hence
      relieving the repression, and stimulates the binding of heterodimers and
      transcription in proportion to the heterodimer binding to the elements. Although
      qualitatively similar in these regards, there were important quantitative
      differences between both TREs. The upTRE binds more T3R homodimers and less T3R
      RXR heterodimers than the dnTRE, and T3 more readily facilitates heterodimer
      binding to the dn- than to the upTRE. These in vitro characteristics are
      reflected in a lower efficiency of T3 to relieve T3R homodimer-mediated
      repression and to stimulate transcription through up-than through dnTRE. There
      were also significant interactions between the two TREs both in the binding of
      the receptors, T3R and RXR, and in the responsiveness to T3. By itself, each TRE
      responded modestly to T3, upTRE with lower sensitivity and dnTRE with higher
      sensitivity than traditional TREs, whereas together, in the context of the gene
      sequence, they mediated a response greater than the sum of those mediated by each
      TRE separately, with an intermediate sensitivity to T3. Thus, two TREs that are
      inadequate to explain the responsiveness of the UCP gene to T3, together form a
      complex unit appropriate for the regulation of the gene by thyroid hormone. These
      interactions represent yet another way TREs can shape up the responsiveness of
      genes to thyroid hormone.

PMID- 8754778
TI  - A complex retinoic acid response element in the uncoupling protein gene defines a
      novel role for retinoids in thermogenesis.
AB  - Retinoids have been implicated in the control of cell proliferation and
      differentiation, and in several developmental processes. We report here the
      molecular bases for a metabolic role of RA, by showing that the expression of the
      uncoupling protein (UCP), the key element in brown adipose tissue (BAT)
      thermogenesis, is stimulated by retinoic acid (RA). Both all-trans-RA and 9-cis
      RA powerfully increase UCP messenger RNA levels in isolated rat brown adipocytes.
      Transient transfection experiments in HIB-1B cells, a BAT-derived cell line,
      identified the sequence -2399/-2490 (called R90) as the RA-responsive sequence in
      the rat UCP gene. R90 mediated a 20- to 70-fold stimulation of the
      chloramphenicol acetyl transferase reporter gene by maximal concentrations of all
      trans-RA or 9-cis-RA. Non-BAT cells were significantly less responsive. RA effect
      was also less when chloramphenicol acetyl transferase gene was driven by a
      heterologous promoter instead of the UCP minimal promoter. By footprinting and
      site-directed mutagenesis, we identified three discrete sequences as being
      essential for the RA response within R90, thus defining the complex RA response
      element (RARE) of this gene. Critical bases in these sequences are arranged in
      pairs of putative half-sites. RAR gamma-RXR heterodimers can bind to the R90 as
      revealed by electrophoretic mobility shift assays using in vitro translated
      receptors, and HIB-1B nuclear extracts with anti-RAR gamma or anti-RXR
      antibodies. The participation of RAR gamma-RXR heterodimers in RA stimulation is
      further supported by transient transfection experiments overexpressing selected
      receptors and dose-response analyses of RA isomers and analogues. These results
      show that retinoids strongly stimulate the rat UCP gene expression through a
      complex RARE, composed of three pairs of half-sites, and define a novel role for
      retinoids in the regulation of facultative thermogenesis and energy expenditure.

PMID- 8754779
TI  - Localization of gamma-aminobutyric acid and glutamic acid decarboxylase in the
      pancreas of the nonobese diabetic mouse.
AB  - Glutamic acid decarboxylase (GAD), among other potential autoantigens, is thought
      to play a crucial role in type I diabetes, particularly in a spontaneous model of
      the disease, the nonobese diabetic (NOD) mouse. In the pancreas, the presence of
      GAD and gamma-aminobutyric acid (GABA), the decarboxylation product of GAD and a
      putative neurotransmitter in the islets of Langerhans, is well documented in the
      beta-cells. This is particularly true in rats, in which another GABAergic
      structure exists near the islets, the neuronal bodies. In this study, first the
      GABA content was measured in isolated islets from NOD and C57BL/6 mice
      (controls), and a decrease was found in NOD females as their insulitis
      progressed. Second, for the first time in mice, confocal analysis of
      immunofluorescent-labeled pancreatic sections revealed near the islets neuronal
      structures in which GAD and neuropeptide Y were colocalized, as they are in the
      brain. These structures were always observed in the pancreata of both sexes of
      C57BL/6 mice at the various ages investigated. In NOD mice, however, these
      neuronal structures were only detected in young females ( < 10 weeks old) and in
      males until an intermediate age. Moreover, patches of T cells surrounding GAD
      containing fibers were seen in the vicinity of the islets with incipient
      periinsulitis.

PMID- 8754780
TI  - Evolution of transthyretin gene expression in the liver of Didelphis virginiana
      and other American marsupials.
AB  - The occurrence of the thyroid hormone-binding plasma protein transthyretin in the
      bloodstream was investigated for four American marsupial species. Serum samples
      were analyzed by incubation with radioactive T4, followed by electrophoresis,
      then autoradiography, and Western blotting. Transthyretin was found in serum from
      Monodelphis domestica, Didelphis virginiana, Caluromys lanatus, and Dromiciops
      australis. For unambiguous identification, transthyretin from D, virginiana was
      purified from serum and its N-terminal amino acid sequence was determined. The
      obtained results suggest that the initiation of transthyretin gene expression in
      the liver of marsupials occurred independently in several lineages of American
      marsupials, all of which are at the ends of phylogenetic branches. The expression
      of the transthyretin gene in the liver of the American polyprotodont marsupials
      contrasts with the lack of transthyretin gene expression in the liver of all 22
      previously investigated Australian Polyprotodonta.

PMID- 8754781
TI  - Dopamine withdrawal elicits prolonged calcium rise to support prolactin rebound
      release.
AB  - Dopamine (DA) acts directly on pituitary lactotropes to inhibit the release of
      PRL. Removal of DA elicits a pronounced transient rise in PRL release to values
      exceeding pre-DA rates (PRL rebound). Electrophysiological studies have shown
      that lactotropes exhibit a period of increased Ca2+ action potential activity
      after DA withdrawal, leading to the proposal that enhanced Ca2+ influx during
      this period may support the rebound secretion of PRL. In the present studies, we
      investigated the effect of DA application and removal on the cytosolic free
      calcium concentration ([Ca2+]i) monitored by fura-2 in single rat lactotropes.
      Unchallenged lactotropes fell into two functionally distinct groups: those with
      stable [Ca2+]i that was not acutely sensitive to extracellular Ca2+, and those
      with spontaneous fluctuations in [Ca2+]i that were dependent upon influx of
      external Ca2+. There was striking variability in the [Ca2+]i patterns of the
      latter group, ranging from irregular, low amplitude fluctuations to rhythmic,
      repetitive oscillations with definable rise and decay kinetics. Application of DA
      resulted in a rapid decrease in [Ca2+]i concomitant with the cessation of these
      spontaneous [Ca2+]i fluctuations. After DA removal, these cells resumed
      oscillatory [Ca2+]i activities similar to those observed before DA application.
      In quiescent lactotropes, acute application of DA exerted no effect on resting
      [Ca2+]i, but quiescent cells could be activated to produce [Ca2+]i fluctuations
      by the application and withdrawal of DA. Again, the character of the induced
      [Ca2+] activity showed significant cell to cell variation. In contrast, the
      pattern of [Ca2+]i fluctuations was remarkably characteristic in a given cell in
      response to repeated challenges. A composite [Ca2+]i profile of 13 cells
      paralleled the PRL secretory rebound after application and removal of DA. The
      oscillatory rise in [Ca2+]i is functionally linked to the rebound release of PRL
      after DA removal, as both were immediately abolished by blockade of Ca2+ influx.
      These data demonstrate that the rebound secretion of PRL is dependent upon
      enhanced influx of extracellular Ca2+ after cells recover from DA-induced
      hyperpolarization and support the hypothesis that a population of inactivated
      Ca2+ channels has been recruited in response to application and withdrawal of DA.

PMID- 8754782
TI  - Effect of 3,5,3'-triiodothyronine on maturation of rat renal phosphate transport:
      kinetic characteristics and phosphate transporter messenger ribonucleic acid and
      protein abundance.
AB  - The plasma concentration of T3 increases during the third postnatal week in rats
      when the young are weaned. Renal phosphate (Pi) transport matures during this
      period, with increases in the carrier affinity for Na-cotransported Pi(1/K(m))
      and in the maximal transport rate (Vmax). As prevention of weaning prevents the
      normal increase in the plasma T3 concentration and blocks the maturation of Pi
      transport, this study examines the influence of T3 on Pi transport maturation.
      The brush border membranes from 21-day-old rats rendered hypothyroid with 6-n
      propyl-2-thiouracil (PTU) or prevented from weaning (PW) were examined. These two
      treatments effectively prevented normal maturation, as the apparent K(m) was
      significantly higher in the PTU (0.243 +/- 0.04) and PW (0.159 +/- 0.008) rats
      than in controls [0.111 +/- 0.032 (n = 6; P < 0.05) and 0.104 +/- 0.005 (n = 6; P
      < 0.05)], and the Vmax was significantly lower [3192 +/- 170 vs. 4269 +/- 343 (n
      = 6; P < 0.01) and 3479 +/- 478 vs. 4184 +/- 368 (n = 6; P < 0.05)].
      Administration of T3 to PTU and PW rats restored the apparent K(m) and V(max) to
      control values. The amounts of Na-Pi co-transporter messenger RNA and protein
      were also determined. The amounts of NaPi-2 messenger RNA and protein were
      decreased about 5-fold in PTU and PW rats, and T3 restored them to control
      levels. The effect of T3 on the maturation of Pi transport was independent of
      PTH, GH, or glucocorticoids. Thus, thyroid hormone helps control the maturation
      of Pi transport in the rat during weaning, and thyroid hormone may be a dominant
      triggering factor in this process.

PMID- 8754783
TI  - Nitric oxide decreases estradiol synthesis of rat luteinized ovarian cells:
      possible role for nitric oxide in functional luteal regression.
AB  - This study was designed to examine the synthesis and function of nitric oxide
      during follicular development and luteinization in the rat ovary. Cells were
      obtained from hypophysectomized diethylstilbestrol-implanted immature female rats
      subjected to several hormonal regimens that resulted in preantral, Graafian,
      ovulatory, atretic, or luteinized ovaries. Cells obtained from ovaries at all
      stages of follicular development synthesized nitric oxide in a linear manner over
      time. The basal production of nitric oxide was 6- to 14-fold higher (P < 0.009)
      in cells obtained from luteinized ovaries than that in cells obtained from
      ovaries at all other developmental stages. Inhibiting endogenous nitric oxide
      synthesis in cells obtained from luteinized ovaries resulted in a 3-fold increase
      (P < 0.007) in the estradiol level without affecting progesterone synthesis. We
      used isoform-specific antisera to determine the cellular location and isoform(s)
      of nitric oxide synthase expressed in our cell culture system and in the
      luteinized ovary in vivo. Positive immunofluorescent staining for both the
      endothelial and inducible isoforms was observed in separate cell types.
      Immunoblotting experiments also showed that luteinized ovaries express the
      endothelial and inducible isoforms of nitric oxide synthase. Nitric oxide
      synthesis inhibits estradiol synthesis in vitro. We suggest that nitric oxide
      participates in functional luteal regression by inhibiting steroidogenesis.

PMID- 8754784
TI  - E2A gene products are not required for insulin gene expression.
AB  - Transcripts for E2A gene products, ubiquitous basic helix-loop-helix
      transactivating proteins, are expressed at high levels in the pancreatic
      epithelium. E2A proteins have been shown to bind the cognate E box sequence
      (CANNTG) of the insulin promoter/enhancer. E2A gene products dimerize with cell
      specific basic helix-loop-helix proteins and synergize with the homeodomain
      transcription factor, PDX-1, in insulin gene transactivation. PDX-1 is also
      required for normal pancreatic development in mice. We investigated whether
      pancreatic development and insulin production could occur in the absence of E2A
      gene products by studying mice with a null mutation for the gene. E2A(-/-) mice
      demonstrated normal formation of pancreatic endocrine and exocrine tissue in
      histochemical sections as well as positive and distinct immunostaining for
      insulin and glucagon in islet tissue, signifying development of mature beta- and
      alpha-cells. Moreover, E2A(-/-) mice displayed no significant difference in blood
      glucose levels or pancreatic insulin content compared with wild-type littermates.
      These data show that although E2A gene products probably play an important role
      in insulin gene expression, pancreatic development and insulin production can
      proceed in their absence.

PMID- 8754785
TI  - Novel ipriflavone receptors coupled to calcium influx regulate osteoclast
      differentiation and function.
AB  - Ipriflavone (7-isopropoxyisoflavone) is an effective antiresorptive agent used to
      treat osteoporosis. However, the mechanism of its action on osteoclasts and their
      precursor cells is not well understood. To determine whether the mechanism
      involves direct effects on osteoclasts or their precursors, we examined the
      effects of ipriflavone on cytosolic free calcium ([Ca2+]i) in osteoclasts and
      their precursors and measured specific binding of 3H-labeled ipriflavone. Highly
      purified chicken osteoclast precursors, which spontaneously differentiate into
      multinucleated osteoclasts in 3-6 days, were loaded with fura-2, and the
      subcellular [Ca2+]i distribution was monitored by videoimaging. Ipriflavone
      induced a rapid increase in [Ca2+]i followed by a sustained elevation [EC50 = 5 x
      10(-7) M, 263 +/- 74 nM (SE) (n = 8) above basal levels, by 10(-6) M ipriflavone,
      sustained phase]. The responses were the same in differentiated chicken
      osteoclasts and isolated rabbit osteoclasts. An influx of extracellular Ca2+ is
      likely to be responsible for the ipriflavone-induced change in [Ca2+]i because
      the response was abolished by 0.5 mM LaCl3, or by Ca-free medium containing EGTA.
      Moreover, high [Ca2+]i levels were detected adjacent to the cell membrane after
      ipriflavone addition. Ipriflavone induced Ca influx mainly through
      dihydropyridine-insensitive Ca2+ channels, because nicardipine (10(-7)M) and
      verapamil (10(-7)M) had no effects on ipriflavone-induced [Ca2+]i responses.
      [3H]Ipriflavone binding studies indicated the presence of specific ipriflavone
      binding sites (two classes), both in precursor cells [dissociation constant (Kd),
      7.60 x 10(-8)M, 2.67 x 10(-6)M] and in mature osteoclasts (Kd, 4.98 x 10(-8)M,
      3.70 x 10(-6)M). Specific ipriflavone binding was not displaced by various
      modulators of avian osteoclast function, such as estradiol (10(-8)M) or retinoic
      acid (10(-6)M), indicating that ipriflavone receptors differ from the receptors
      for these Ca-regulating hormones. The fusion of osteoclast precursor cells was
      significantly inhibited by ipriflavone, which led to dose-dependent inhibition of
      bone resorption and tartrate-resistant acid phosphatase activity. Novel specific
      ipriflavone receptors that are coupled to Ca2+ influx were demonstrated in
      osteoclasts and their precursor cells. These ipriflavone receptors may provide a
      mechanism to regulate osteoclast differentiation and function.

PMID- 8754787
TI  - Effects of growth factors and interleukin-1 alpha on proteoglycan and type II
      collagen turnover in bovine nasal and articular chondrocyte pellet cultures.
AB  - The aim of this study was to investigate the effects of insulin-like growth
      factor-I, transforming growth factor-beta (TGF-beta), and interluekin-1 alpha (IL
      1 alpha) on the deposition and degradation of a cartilage-like matrix in high
      density pellet cultures of adult bovine chondrocytes. Proteoglycan was determined
      by toluidine blue staining and colorimetric assay. Type II collagen was
      determined by immunohistochemical staining and its unwinding in situ by a
      recently developed immunoassay. Bovine nasal chondrocytes cultured as pellets
      deposited a well-organized extracellular matrix of proteoglycan and type II
      collagen. Insulin-like growth factor-I (2-10 ng/ml) increased the synthesis and
      incorporation into the matrix of both these proteins. TGF-beta (2-10 ng/ml) also
      increased proteoglycan synthesis. However it inhibited proteoglycan deposition,
      presumably through increased degradation of the molecule, as shown by increased
      release of aggrecan fragments into the tissue culture medium. TGF-beta had no
      effect on type II collagen deposition. In pellet cultures of bovine nasal or
      articular chondrocytes, 20 ng/ml IL-1 alpha induced a significant degradation of
      both proteoglycan and type II collagen. The effect on collagen clearly involved
      proteolytic cleavage of its triple helix because there was an increase in the
      proportion of unwound type II collagen in the matrix, as well as a loss of total
      type II collagen. In explant cultures of intact bovine articular cartilage,
      incubation with 50 ng/ml IL-1 alpha stimulated significant degradation of the
      proteoglycan but no degradation of the type II collagen. These results
      demonstrate that although the articular chondrocytes are capable of degrading
      type II collagen when isolated, they do not do so in situ, presumably because of
      some inherent property of the mature extracellular matrix. This study
      demonstrates the utility of pellet cultures when investigating chondrocyte
      mediated turnover of cartilage matrix and its modulation by cytokines and growth
      factors.

PMID- 8754786
TI  - Insulin-like growth factor binding proteins in fetal rat mesencephalic cultures:
      regulation by fibroblast growth factor and insulin-like growth factor I.
AB  - In rat ventral mesencephalic cultures, IGF-I and bovine fibroblast growth factor
      (bFGF) act cooperatively to support the survival of dopaminergic neurons. To
      determine the potential role of IGFBPs in modulating the actions of IGF-I in the
      ventral mesencephalon, we identified the IGFBPs present in ventral mesencephalic
      cultures and examined their regulation by IGF-I and bFGF. In the absence of added
      growth factors, the major binding protein secreted from these cultures was IGFBP
      2. Small amounts of IGFFBP-3 and IGFBP-4 were also detected. Addition of bFGF to
      the cultures increased the amounts of IGFBP-3 and IGFBP-4 released from the cells
      by 4.4 +/- 2.6 -fold (P < 0.1) and 11.5 +/- 3.5 -fold (P < 0.05), respectively.
      IGF-I, itself, had little effect on the production of IGFBPs, but when added
      together with bFGF increased the levels of IGFBP-3 and IGFBP-4 by 12.4 +/- 5.1 
      fold (P < 0.05) and 27.4 +/- 5.3 -fold (P < 0.02), respectively. The stimulatory
      effect of bFGF and IGF-I on IGFBP production was apparent after a 2- to 3-day
      exposure of the mesencephalic cultures to the peptides. IGFBP-4, the most
      abundant IGFBP present in the cultures after 7 days of growth factor treatment,
      was immunocyto-chemically localized primarily to neurons, of which a subset were
      dopaminergic neurons. The addition of purified rat IGFBP-4 to the cultures in the
      absence of added growth factors had no effect on the survival of dopaminergic
      neurons, but when added with IGF-I potentiated the effect of IGF-I on neuronal
      survival. We propose that the up-regulation of IGFBP-4 by IGF-I and bFGF may
      serve to localize IGF-I to sites of action in the nervous system and thereby
      potentiate the neurotrophic actions of IGF-I.

PMID- 8754788
TI  - Angiotensin II regulation of tyrosine hydroxylase gene expression in the neuronal
      cultures of normotensive and spontaneously hypertensive rats.
AB  - In the present study we investigated the regulation of tyrosine hydroxylase (TH)
      by angiotensin II (Ang II) in an attempt to provide cellular and molecular
      evidence that this hormone has increased neuromodulatory actions in the
      spontaneously hypertensive (SH) rat brain. Neuronal cells in primary culture from
      the hypothalamus-brain stem of both normotensive [Wistar-Kyoto (WKY)] and SH rats
      have been used. These cultures mimic in vivo situations. Ang II caused a time
      dependent increase in TH activity in WKY rat brain neurons. A maximal increase of
      2.5-fold was observed with 100 nM Ang II in an actinomycin- and cycloheximide
      dependent process. In addition, Ang II caused a parallel increase in TH messenger
      RNA (mRNA) levels, with a maximal stimulation of 5-fold in 4 h by 100 nM Ang II
      in WKY rat brain neurons. The stimulation of TH mRNA was mediated by the AT1
      receptor subtype, resulted from an increase in its transcription, and involved
      activation of phospholipase C and protein kinase C. Antisense oligonucleotide for
      c-fos attenuated Ang II stimulation of TH mRNA in a time- and dose-dependent
      fashion, indicating an involvement of c-fos as a putative third messenger in Ang
      II stimulation of TH. Ang II also caused stimulation of TH activity and its mRNA
      levels in neuronal cultures of SH rat brain by a mechanism similar to that
      observed for neuronal cultures of WKY rat brain, involving AT1 receptors, protein
      kinase C, and c-fos. However, the stimulation of TH activity and that of TH mRNA
      were approximately 30% and 80% higher, respectively, in the SH rat brain neurons
      than those in the WKY rat brain neurons. In vivo experiments have been carried
      out to validate the elevated response of TH gene expression to Ang II in SH rat
      brain neuronal cultures. Ang II stimulated both TH activity and TH mRNA levels in
      the hypothalami and brain stems of adult WKY and SH rats. The level of
      stimulation in the brain of the SH rat was significantly higher than that in the
      WKY rat. These observations are consistent with an increase in AT1, receptor gene
      expression and suggest that increased TH gene expression could be the
      cellular/molecular basis for the greater neuromodulatory action of Ang II in the
      SH rat brain.

PMID- 8754789
TI  - In situ investigation of vitamin D receptor, alkaline phosphatase, and
      osteocalcin gene expression in oro-facial mineralized tissues.
AB  - The aim of this study was to investigate the expression pattern of 1, 25
      dihydroxyvitamin D3 receptor (VDR) and vitamin D-responsive gene expression
      during the steps of hard tissue formation in oro-facial development. In situ
      hybridization of VDR, alkaline phosphatase, and osteocalcin transcripts was
      performed in the mandibles of growing rats. Osteoblasts were used as the internal
      positive control for in situ detection of VDR messenger RNAs. Transcripts were
      present throughout the stages of differentiation and in differentiated
      osteoblasts and osteocytes, and showed some anatomical specificities in their
      developmental expression pattern. In dental tissues, VDR was strongly expressed
      in the inner dental epithelium at the beginning of the presecretion stage and,
      after a transient decrease at the end of the presecretion stage, in secretion
      stage ameloblasts. VDR was continuously expressed in epithelial supraameloblastic
      cells. During dentin formation, VDR was mainly present in subodontoblastic cells
      and was down-regulated during the terminal differentiation of odontoblasts. In
      these cells, VDR expression appeared to be induced by 1, 25-dihydroxyvitamin D3
      injection. These data confirm that VDR is expressed in cells directly involved in
      mineralized tissue formation: ameloblasts, odontoblasts, and osteoblasts.
      Furthermore, they extend the idea of vitamin D sensitivity to cells that are not
      directly involved in this process: supraameloblastic, subodontoblastic, and
      osteoprogenitor cells. The differential expression pattern of VDR in odontoblasts
      and osteoblasts together with the similarity in the expression of potential
      vitamin D-responsive genes (osteocalcin in odontoblasts and osteoblasts, and
      alkaline phosphatase in osteoprogenitor and subodontoblastic cells) suggest the
      existence of a tissue specificity for the genomic action of 1, 25
      dihydroxyvitamin D3, which may involve co-operation with additional nuclear
      factors.

PMID- 8754790
TI  - Differential patterns of expression of DAX-1 and steroidogenic factor-1 (SF-1) in
      the fetal rat testis.
AB  - Gonadal differentiation is dependent upon a cascade of molecular and
      morphological events. Steroidogenic factor 1 (SF-1) and DAX-1 have been
      implicated in this process. A SF-1 binding site has been reported to be present
      on the DAX-1 gene. We therefore used immunocytochemistry to determine whether
      these two transcription factors are co-expressed in the fetal testis. DAX-1 was
      immunolocalised to the cytoplasm of interstitial cells from fetal testis of rat
      and human from day 15.5 and 16 weeks of gestation respectively. SF-1 was detected
      in nuclei of fetal Sertoli and interstitial cells. In the fetal rat expression of
      SF-1 in interstitial cells was not uniform; cells with abundant SF-1 all
      contained 3-beta HSD and were classified as Leydig cells. DAX-1 expression was
      not exclusive to cells which contained SF-1 and SF-1/DAX-1 co-expressing cells
      were not exclusively fetal Leydig cells. We conclude that in the fetal testis
      expression of the DAX-1 protein is not dependent upon the presence of SF-1
      although SF-1 is present at an earlier stage of gestation in the gonad. DAX-1 may
      therefore play a separate or complementary role to that of SF-1 in the modulation
      of testicular gene expression and differentiation.

PMID- 8754791
TI  - Expression of a constitutively activated form of protein kinase B (c-Akt) in 3T3
      L1 preadipose cells causes spontaneous differentiation.
AB  - Insulin/IGF-1 is required for differentiation of 3T3-L1 adipose cells. Downstream
      targets of insulin/IGF-1 that lead to adipocyte differentiation appear to include
      Ras, phosphatidylinositol (PI) 3-kinase, Raf, and mitogen-activated protein
      kinase. We have tested whether protein kinase B (PKB), a serine/threonine kinase
      activated by PI 3-kinase, is sufficient for 3T3-L1 preadipose cell
      differentiation. A plasmid vector encoding a version of PKB that is
      constitutively activated (Gag-PKB) was expressed in 3T3-L1 preadipose cells (Gag
      PKB cells). Spontaneous morphological changes indicative of adipocyte
      differentiation were observed in Gag-PKB cells. The cells assumed a spherical
      shape and they acquired characteristic lipid droplets that stained positively for
      Oil Red O. Northern blot analysis detected upregulation of LPL and aP2 mRNA,
      specific indicators of adipocyte differentiation. Our data demonstrate that
      constitutive activation of PKB is sufficient to trigger adipocyte
      differentiation.

PMID- 8754792
TI  - Molecular cloning and properties of a full-length putative thyroid hormone
      receptor coactivator.
AB  - Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that
      regulate target gene transcription. The conserved carboxy-terminal region of the
      ligand-binding domain (AF-2) has been thought to play a critical role in
      mediating ligand-dependent transactivation by the interaction with
      coactivator(s). Using bacterially-expressed TR as a probe, far-Western-based
      expression cDNA library screening identified cDNAs that encode, in part, the
      recently reported partial steroid receptor coactivator-1 (SRC-1) sequence.
      Additional work, including 5' RACE, has characterized a full-length cDNA that
      encodes a approximately 160 kD protein as a putative thyroid hormone receptor
      coactivator (F-SRC-1). In vitro binding studies show that F-SRC-1 binds to a
      variety of nuclear hormone receptors in a ligand-dependent manner, along with TBP
      and TFIIB, suggesting that F-SRC-1 may play a role as a bridging molecule between
      nuclear hormone receptors and general transcription factors. Interestingly, AF-2
      mutants also retain ligand-dependent interaction with F-SRC-1. Although F-SRC-1
      recognizes the ligand-induced conformational changes of nuclear hormone
      receptors, our observations suggest that F-SRC-1 may bind directly with
      subregion(s) in nuclear hormone receptors other than the AF-2 region.

PMID- 8754793
TI  - Reproduction in mice lacking a functional type 1 IL-1 receptor.
AB  - Growth factors and cytokines have been identified in having critical roles at
      mediating maternal-fetal interactions during pregnancy, with interleukin-1 being
      a recently implicated factor. Previous experiments indicated that repeated
      intraperitoneal injections of the Il-1 receptor antagonist (Il-1Ra), which
      inhibits binding of interleukin-1 (Il-1) to the type 1 Il-1 receptor (Il-1Rt1)
      blocks blastocyst implantation in superovulated mice. To gain a greater insight
      into the role of Il-1 receptor in implantation, we analyzed the reproduction of
      mice deficient for the Il-1Rt1. Our results show that mice lacking this receptor
      do not exhibit any profound alterations in their reproduction, apart from a
      slight reduction in mean litter size. Furthermore, repeated intraperitoneal
      injections of either IL-1Ra or the monoclonal antibody 35F5, which also blocks
      ligand binding to the Il-1Rt1, did not affect embryo implantation in either wild
      type and Il-1 receptor deficient mice.

PMID- 8754794
TI  - Gonadotropin releasing hormone agonist provokes homologous receptor
      microaggregation: an early event in seven-transmembrane receptor mediated
      signaling.
AB  - Gonadotropin releasing hormone (GnRH) mediates interactions between the neural
      and the endocrine systems. The GnRH receptor is a member of the ubiquitous seven
      transmembrane segment G-protein-coupled receptor class and is the target of drug
      development for treatment of breast and prostate cancer, regulation of fertility,
      endometriosis and a range of other medical and veterinary uses. This study shows
      that occupancy of the receptor by an agonist (but not an antagonist) promotes
      receptor-receptor interactions which appears to be an early event in hormone
      action.

PMID- 8754795
TI  - Osteoclast function is activated by osteoblastic cells through a mechanism
      involving cell-to-cell contact.
AB  - We have established a method for obtaining an enriched preparation of
      functionally active osteoclast-like multinucleated cells (enriched OCLs) from co
      cultures of mouse primary osteoblasts and bone marrow cells. Using these enriched
      OCLs, the effect of osteoblastic cells on osteoclast function was examined in two
      assays: a pit formation assay and an assay for actin ring formation. The enriched
      OCLs cultured for 24 h on dentine slices formed only a few resorption pits. When
      various numbers of primary osteoblasts were added to the enriched OCLs, the areas
      of the resorption pits increased proportionally to the number of osteoblasts
      added. Like primary osteoblasts, the established cell lines of osteoblastic cell
      (MC3T3-E1 and KS-4) and bone marrow-derived stromal cells (MC3T3-G2/PA6 and ST2)
      potentiated the pit formation caused by enriched OCLs. In contrast, the
      fibroblastic cell lines (NIH3T3 and C3H10T1/2) and the myoblastic cell line
      (C2C12) failed to activate OCL function. When cell-to-cell contact between MC3T3
      E1 cells and enriched OCLs was prevented, only a few resorption pits were formed.
      Pit formation by enriched rat osteoclasts placed on dentine slices was also
      stimulated by adding MC3T3-E1 cells. Actin ring formation and pit forming
      activity were well correlated in either culture of enriched mouse OCLs or
      authentic rat osteoclasts on dentine slices. These results indicate that
      osteoclast function is activated by osteoblastic cells-through a mechanism
      involving cell-to-cell and/or cell-to-matrix contact.

PMID- 8754796
TI  - Transcriptional regulation of a sterol-biosynthetic enzyme by sterol levels in
      Saccharomyces cerevisiae.
AB  - Sterols and all nonsterol isoprenoids are derived from the highly conserved
      mevalonate pathway. In animal cells, this pathway is regulated in part at the
      transcriptional level through the action of sterol response element-binding
      proteins acting at specific DNA sequences near promoters. Here we extend at least
      part of this regulatory paradigm to the ERG10 gene, which encodes a sterol
      biosynthetic enzyme of Saccharomyces cerevisiae. Specifically, the discovery of
      sterol-mediated feedback control of ERG10 transcription is reported. Deletion
      analysis of the ERG10 promoter region identified sequences involved in the
      expression of ERG10. This regulatory axis appeared to involve sterol levels, as a
      late block in the pathway that depletes sterol, but not nonsterol isoprenoids,
      was able to elicit the regulatory response.

PMID- 8754797
TI  - Kar4p, a karyogamy-specific component of the yeast pheromone response pathway.
AB  - Karyogamy is the process whereby two haploid nuclei fuse to form a diploid
      nucleus during mating in Saccharomyces cerevisiae. Here, we describe the
      characterization of the KAR4 gene, previously identified in a screen for new
      nuclear fusion-defective mutants. During mating, kar4 mutants were defective for
      the microtubule-dependent movement of nuclei, a phenotype identical to that of
      mutations in KAR3 and CIK1. Consistent with its mutant phenotype, we found that
      the kar4 mutation resulted in failure to induce KAR3 and CIK1 mRNA during mating.
      Expression of KAR3 and CIK1 under independent regulatory control suppressed the
      kar4 defect, indicating that KAR4 is required primarily for the induction of KAR3
      and CIK1. KAR4 was also required for meiosis, during which it may regulate KAR3;
      however, mitotic expression of KAR3 and CIK1 during S/G2 phase was independent of
      KAR4. A 30-bp region upstream of KAR3 conferred both KAR4- and STE12-dependent
      induction by mating pheromone. This region contained one moderate and two weak
      matches to the consensus pheromone response element to which the Ste12p
      transcriptional activator binds and five repeats of the sequence CAAA(A).
      Overproduction of Ste12p suppressed the kar4 defect in KAR3 induction and nuclear
      fusion. In contrast, Ste12p-independent expression of Kar4p did not alleviate the
      requirement for Ste12p during KAR3 induction. We propose that Kar4p assists
      Ste12p in the pheromone-dependent expression of KAR3 and CIK1. KAR4 defines a
      novel level of regulation for the pheromone response pathway, acting at a subset
      of Stel2p-inducible genes required for karyogamy.

PMID- 8754798
TI  - Determination of functional domains in the C subunit of the CCAAT-binding factor
      (CBF) necessary for formation of a CBF-DNA complex: CBF-B interacts
      simultaneously with both the CBF-A and CBF-C subunits to form a heterotrimeric
      CBF molecule.
AB  - The mammalian CCAAT-binding factor (CBF; also called NF-Y and CP1) is a
      heterotrimeric protein consisting of three subunits, CBF-A, CBF-B, and CBF-C, all
      of which are required for DNA binding and all of which are present in the CBF-DNA
      complex. In this study using cross-linking and immunoprecipitation methods, we
      first established that CBF-B interacts simultaneously with both subunits of the
      CBF-A-CBF-C heterodimer to form a heterotrimeric CBF molecule. We then performed
      a mutational analysis of CBF-C to define functional interactions with the other
      two CBF subunits and with DNA using several in vitro assays and an in vivo yeast
      two-hybrid system. Our experiments established that the evolutionarily conserved
      segment of CBF-C, which shows similarities with the histone-fold motif of histone
      H2A, was necessary for formation of the CBF-DNA complex. The domain of CBF-C
      which interacts with CBF-A included a large portion of this segment, one that
      corresponds to the segment of the histone-fold motif in H2A used for interaction
      with H2B. Two classes of interactions involved in formation of the CBF-A-CBF-C
      heterodimer were detected; one class, provided by residues in the middle of the
      interaction domain, was needed for formation of the CBF-A-CBF-C heterodimer. The
      other, provided by sequences flanking those of the first class was needed for
      stabilization of the heterodimer. Two separate domains were identified in the
      conserved segment of CBF-C for interaction with CBF-B; these were located on each
      side of the CBF-A interaction domain. Since our previous experiments identified a
      single CBF-B interaction domain in the histone-fold motif of CBF-A, we propose
      that a tridentate interaction domain in the CBF-A-CBF-C heterodimer interacts
      with the 21-amino-acid-long subunit interaction domain of CBF-B. Together with
      our previous mutational analysis of CBF-A (S. Sinha, I.-S. Kim, K.-Y. Sohn, B. de
      Crombrugghe, and S. N. Maity, Mol. Cell. Biol. 16:328-337, 1996), this study
      demonstrates that the histone fold-motifs of CBF-A and CBF-C interact with each
      other to form the CBF-A-CBF-C heterodimer and generate a hybrid surface which
      then interacts with CBF-B to form the heterotrimeric CBF molecule.

PMID- 8754799
TI  - Muscle-specific splicing enhancers regulate inclusion of the cardiac troponin T
      alternative exon in embryonic skeletal muscle.
AB  - The alternative exon 5 of the striated muscle-specific cardiac troponin T (cTNT)
      gene is included in mRNA from embryonic skeletal and cardiac muscle and excluded
      in mRNA from the adult. The embryonic splicing pattern is reproduced in primary
      skeletal muscle cultures for both the endogenous gene and transiently transfected
      minigenes, whereas in nonmuscle cell lines, minigenes express a default exon
      skipping pattern. Using this experimental system, we previously showed that a
      purine-rich splicing enhancer in the alternative exon functions as a constitutive
      splicing element but not as a target for factors regulating cell-specific
      splicing. In this study, we identify four intron elements, one located
      upstream,and three located downstream of the alternative exon, which act in a
      positive manner to mediate the embryonic splicing pattern of exon inclusion.
      Synergistic interactions between at least three of the four elements are
      necessary and sufficient to regulate splicing of a heterologous alternative exon
      and heterologous splice sites. Mutations in these elements prevent activation of
      exon inclusion in muscle cells but do not affect the default level of exon
      inclusion in nonmuscle cells. Therefore, these elements function as muscle
      specific splicing enhancers (MSEs) and are the first muscle-specific positive
      acting splicing elements to be described. One MSE located downstream from the
      alternative exon is conserved in the rat and chicken cTNT genes. A related
      sequence is found in a third muscle-specific gene, that encoding skeletal
      troponin T, downstream from an alternative exon with a developmental pattern of
      alternative splicing similar to that of rat and chicken cTNT. Therefore, the MSEs
      identified in the cTNT gene may play a role in developmentally regulated
      alternative splicing in a number of different genes.

PMID- 8754800
TI  - Gfi-1 encodes a nuclear zinc finger protein that binds DNA and functions as a
      transcriptional repressor.
AB  - The Gfi-1 proto-oncogene encodes a zinc finger protein with six C2H2-type, C
      terminal zinc finger motifs and is activated by provirus integration in T-cell
      lymphoma lines selected for interleukin-2 independence in culture and in primary
      retrovirus-induced thymomas. Gfi-1 expression in adult animals is restricted to
      the thymus, spleen, and testis and is enhanced in mitogen-stimulated splenocytes.
      In this report, we show that Gfi-1 is a 55-kDa nuclear protein that binds DNA in
      a sequence-specific manner. The Gfi-1 binding site, TAAATCAC(A/T)GCA, was defined
      via random oligonucleotide selection utilizing a bacterially expressed
      glutathione S-transferase-Gfi-1 fusion protein. Binding to this site was
      confirmed by electrophoretic mobility shift assays and DNase I footprinting.
      Methylation interference analysis and electrophoretic mobility shift assays with
      mutant oliginucleotides defined the relative importance of specific bases at the
      consensus binding site. Deletion of individual zinc fingers demonstrated that
      only zinc fingers 3, 4, and 5 are required for sequence-specific DNA binding.
      Potential Gfi-1 binding sites were detected in a large number of eukaryotic
      promoter-enhancers, including the enhancers of several proto-oncogenes and
      cytokine genes and the enhancer of the human cytomegalovirus (HCMV) major
      immediate-early promoter, which contains two such sites. HCMV major immediate
      early-chloramphenicol acetyltransferase reporter constructs, transfected into NIH
      3T3 fibroblasts, were repressed by Gfi-1, and the repression was abrogated by
      mutation of critical residues in the two Gfi-1 binding sites. These results
      suggest that Gfi-1 may play a role in HCMV biology and may contribute to
      oncogenesis and T-cell activation by repressing the expression of genes that
      inhibit these processes.

PMID- 8754801
TI  - Role of the intermembrane-space domain of the preprotein receptor Tom22 in
      protein import into mitochondria.
AB  - Tom22 is an essential component of the protein translocation complex (Tom
      complex) of the mitochondrial outer membrane. The N-terminal domain of Tom22
      functions as a preprotein receptor in cooperation with Tom20. The role of the C
      terminal domain of Tom22, which is exposed to the intermembrane space (IMS), in
      its own assembly into the Tom complex and in the import of other preproteins was
      investigated. The C-terminal domain of Tom22 is not essential for the targeting
      and assembly of this protein, as constructs lacking part or all of the IMS domain
      became imported into mitochondria and assembled into the Tom complex. Mutant
      strains of Neurospora expressing the truncated Tom22 proteins were generated by a
      novel procedure. These mutants displayed wild-type growth rates, in contrast to
      cells lacking Tom22, which are not viable. The import of proteins into the outer
      membrane and the IMS of isolated mutant mitochondria was not affected. Some but
      not all preproteins destined for the matrix and inner membrane were imported less
      efficiently. The reduced import was not due to impaired interaction of
      presequences with their specific binding site on the trans side of the outer
      membrane. Rather, the IMS domain of Tom22 appears to slightly enhance the
      efficiency of the transfer of these preproteins to the import machinery of the
      inner membrane.

PMID- 8754802
TI  - Transcriptional control of a nuclear gene encoding a mitochondrial fatty acid
      oxidation enzyme in transgenic mice: role for nuclear receptors in cardiac and
      brown adipose expression.
AB  - Expression of the gene encoding medium-chain acyl coenzyme A dehydrogenase
      (MCAD), a nuclearly encoded mitochondrial fatty acid beta-oxidation enzyme, is
      regulated in parallel with fatty acid oxidation rates among tissues and during
      development. We have shown previously that the human MCAD gene promoter contains
      a pleiotropic element (nuclear receptor response element [NRRE-1]) that confers
      transcriptional activation or repression by members of the nuclear receptor
      superfamily. Mice transgenic for human MCAD gene promoter fragments fused to a
      chloramphenicol acetyltransferase gene reporter were produced and characterized
      to evaluate the role of NRRE-1 and other promoter elements in the transcriptional
      control of the MCAD gene in vivo. Expression of the full-length MCAD promoter
      chloramphenicol acetyltransferase transgene (MCADCAT.371) paralleled the known
      tissue-specific differences in mitochondrial beta-oxidation rates and MCAD
      expression. MCADCAT.371 transcripts were abundant in heart tissue and brown
      adipose tissue, tissues with high-level MCAD expression. During perinatal cardiac
      developmental stages, expression of the MCADCAT.371 transgene paralleled mouse
      MCAD mRNA levels. In contrast, expression of a mutant MCADCAT transgene, which
      lacked NRRE-1 (MCADCATdeltaNRRE-1), was not enriched in heart or brown adipose
      tissue and did not exhibit appropriate postnatal induction in the developing
      heart. Transient-transfection studies with MCAD promoter-luciferase constructs
      containing normal or mutant NRRE-1 sequences demonstrated that the nuclear
      receptor binding sequences within NRRE-1 are necessary for high-level
      transcriptional activity in primary rat cardiocytes. Electrophoretic mobility
      shift assays demonstrated that NRRE-1 was bound by several cardiac and brown
      adipose nuclear proteins and that these interactions required the NRRE-1 receptor
      binding hexamer sequences. Antibody supershift studies identified the orphan
      nuclear receptor COUP-TF as one of the endogenous cardiac proteins which bound
      NRRE-1. These results dictate an important role for nuclear receptors in the
      transcriptional control of a nuclear gene encoding a mitochondrial fatty acid
      oxidation enzyme and identify a gene regulatory pathway involved in cardiac
      energy metabolism.

PMID- 8754804
TI  - A novel rat homolog of the Saccharomyces cerevisiae ubiquitin-conjugating enzymes
      UBC4 and UBC5 with distinct biochemical features is induced during
      spermatogenesis.
AB  - The Saccharomyces cerevisiae ubiquitin-conjugating enzymes (E2s) UBC4 and UBC5
      are essential for degradation of short-lived and abnormal proteins. We previously
      identified rat cDNAs encoding two E2s with strong sequence similarity to UBC4 and
      UBC5. These E2 isoforms are widely expressed in rat tissues, consistent with a
      fundamental cellular function for these E2s. We now report a new isoform, 8A,
      which despite having >91% amino acid identity with the other isoforms, shows
      several novel features. Expression of the 8A isoform appears restricted to the
      testis, is absent in early life, but is induced during puberty. Hypophysectomy
      reduced expression of the 8A isoform. In situ hybridization studies indicated
      that 8A mRNA is expressed mainly in round spermatids. Immunoblot analyses showed
      that 8A protein is found not only in subfractions of germ cells enriched in round
      spermatids but also in subfractions containing residual bodies extruded from more
      mature elongated spermatids, indicating that the protein possesses a longer half
      life than the mRNA. Unlike all previously identified mammalian and plant homologs
      of S. cerevisiae UBC4, which possess a basic pI, the 8A isoform is unique in
      possessing an acidic pI. The small differences in sequence between the 8A isoform
      and other rat isoforms conferred differences in biochemical function. The 8A
      isoform was less effective than an isoform with a basic pI or ineffective in
      conjugating ubiquitin to certain fractions of testis proteins. Thus, although
      multiple isoforms of a specific E2 may exist to ensure performance of a critical
      cellular function, our data demonstrate, for the first time, that multiple genes
      also permit highly specialized regulation of expression of specific isoforms and
      that subtle differences in E2 primary structure can dictate conjugation of
      ubiquitin to different subsets of cellular proteins.

PMID- 8754803
TI  - The dual effect of adenovirus type 5 E1A 13S protein on NF-kappaB activation is
      antagonized by E1B 19K.
AB  - The genomes of human adenoviruses encode several regulatory proteins, including
      the two differentially spliced gene products E1A and E1B. Here, we show that the
      13S but not the 12S splice variant of E1A of adenovirus type 5 can activate the
      human transcription factor NF-kappaB in a bimodal fashion. One mode is the
      activation of NF-kappaB containing the p65 subunit from the cytoplasmic NF-kappaB
      IkappaB complex. This activation required reactive oxygen intermediates and the
      phosphorylation of IkappaBalpha at serines 32 and 36, followed by IkappaBalpha
      degradation and the nuclear uptake of NF-kappaB. In addition, 13S E1A stimulated
      the transcriptional activity of the C-terminal 80 amino acids of p65 at a core
      promoter with either a TATA box or an initiator (INR) element. The C-terminal 80
      amino acids of p65 were found to associate with E1A in vitro. The activation of
      NF-kappaB-dependent reporter gene transcription by E1A was potently suppressed
      upon coexpression of the E1B 19-kDa protein (19K). E1B 19K prevented both the
      activation of NF-kappaB and the E1A-mediated transcriptional enhancement of p65.
      These inhibitory effects were not found for the 55-kDa splice variant of the E1B
      protein. We suggest that the inductive effect of E1A 13S on the host factor NF
      kappaB, whose activation is important for the transcription of various adenovirus
      genes, must be counteracted by the suppressive effect of E1B 19K so that the
      adenovirus-infected cell can escape the immune-stimulatory and apoptotic effects
      of NF-kappaB.

PMID- 8754805
TI  - Two regions within the DNA binding domain of nuclear factor I interact with DNA
      and stimulate adenovirus DNA replication independently.
AB  - The cellular transcription factor nuclear factor I (NFI) stimulates adenovirus
      DNA replication by up to 50-fold. The NFI DNA binding domain (NFI-BD) is
      sufficient for stimulation and interacts with the viral DNA polymerase, thereby
      recruiting the precursor terminal protein-DNA polymerase complex (pTP-pol) to the
      origin of replication. The mechanism of DNA binding by NFI is unknown. To examine
      DNA binding and stimulation of adenovirus DNA replication by NFI-BD in more
      detail, we generated a series of deletion mutants and show that the DNA binding
      domain of NFI consists of two subdomains: a highly basic N-terminal domain that
      binds nonspecifically to DNA and a C-terminal domain that binds specifically but
      with very low affinity to the NFI recognition site. Both of these subdomains
      stimulate DNA replication, although not to the same extent as the intact DNA
      binding domain. The N-terminal domain has an alpha-helical structure, as shown by
      circular dichroism spectroscopy. The C-terminal domain interacts with the pTP-pol
      complex and is able to recruit the pTP-pol complex to DNA, which leads to pTP-pol
      dependent stimulation of replication. The N-terminal domain also stimulates
      replication in a pTP-pol-dependent manner and enhances binding of pTP-pol to DNA.
      Since we could not detect a direct protein-protein interaction between pTP-pol
      and the N-terminal domain, we suggest that this domain stimulates replication by
      inducing structural changes in the DNA.

PMID- 8754806
TI  - Profound ligand-independent kinase activation of fibroblast growth factor
      receptor 3 by the activation loop mutation responsible for a lethal skeletal
      dysplasia, thanatophoric dysplasia type II.
AB  - Thanatophoric dysplasia type II (TDII) is a neonatal lethal skeletal dysplasia
      caused by a recurrent Lys-650-->Glu mutation within the highly conserved
      activation loop of the kinase domain of fibroblast growth factor receptor 3
      (FGFR3). We demonstrate here that this mutation results in profound constitutive
      activation of the FGFR3 tyrosine kinase, approximately 100-fold above that of
      wild-type FGFR3. The mechanism of FGFR3 activation in TDII was probed by
      constructing various point mutations in the activation loop. Substitutions at
      position 650 indicated that not only Glu but also Asp and, to a lesser extent,
      Gln and Leu result in pronounced constitutive activation of FGFR3. Additional
      mutagenesis within the beta10-beta11 loop region (amino acids Tyr-647 to Leu-656)
      demonstrated that amino acid 650 is the only residue which can activate the
      receptor when changed to a Glu, indicating a specificity of position as well as
      charge for mutations which can give rise to kinase activation. Furthermore, when
      predicted sites of autophosphorylation at Tyr-647 and Tyr-648 were mutated to
      Phe, either singly or in combination, constitutive kinase activity was still
      observed in response to the Lys-650-->Glu mutation, although the effect of these
      mutations on downstream signalling was not investigated. Our data suggest that
      the molecular effect of the TDII activation loop mutation is to mimic the
      conformational changes that activate the tyrosine kinase domain, which are
      normally initiated by ligand binding and autophosphorylation. These results have
      broad implications for understanding the molecular basis of other human
      developmental syndromes that involve mutations in members of the FGFR family.
      Moreover, these findings are relevant to the study of kinase regulation and the
      design of activating mutations in related tyrosine kinases.

PMID- 8754807
TI  - Deletion of an amino-terminal sequence beta-catenin in vivo and promotes
      hyperphosporylation of the adenomatous polyposis coli tumor suppressor protein.
AB  - Regulation of cell adhesion and cell signaling by beta-catenin occurs through a
      mechanism likely involving the targeted degradation of the protein. Deletional
      analysis was used to generate a beta-catenin refractory to rapid turnover and to
      examine its effects on complexes containing either cadherin or the adenomatous
      polyposis coli (APC) protein. The results show that amino-terminal deletion of
      beta-catenin results in a protein with increased stability that acts in a
      dominant fashion with respect to wild-type beta-catenin. Constitutive expression
      in AtT20 cells of a beta-catenin lacking 89 N-terminal amino acids (deltaN89beta
      catenin) resulted in severely reduced levels of the more labile wild-type beta
      catenin. The mutant beta-catenin was expressed at endogenous levels but displaced
      the vast majority of wild-type beta-catenin associated with N-cadherin. The
      deltaN89beta-catenin accumulated on the APC protein to a level 10-fold over that
      of wild-type beta-catenin and recruited a kinase into the APC complex. The kinase
      was highly active toward APC in vitro and promoted a sodium dodecyl sulfate gel
      band shift that was also evident for endogenous APC from cells expressing the
      mutant beta-catenin. Unlike wild-type beta-catenin, which partitions solely as
      part of a high-molecular-weight complex, the deltaN89 mutant protein also
      fractionated as a stable monomer, indicating that it had escaped the requirement
      to associate with other proteins. That similar N-terminal mutants of beta-catenin
      have been implicated in cellular transformation suggests that their abnormal
      association with APC may, in part, be responsible for this phenotype.

PMID- 8754808
TI  - The SH3-domain protein Bem1 coordinates mitogen-activated protein kinase cascade
      activation with cell cycle control in Saccharomyces cerevisiae.
AB  - The mating mitogen-activated protein kinase (MAPK) cascade has three major
      outputs prior to fusion: transcriptional activation of many genes, cell cycle
      arrest in the G1 phase, and polarized growth. Bem1 localizes near the cortical
      actin cytoskeleton and is essential for polarized growth during mating. Here we
      show that Bem1 is required for efficient signal transduction and coordinates MAPK
      cascade activation with G1 arrest and mating. bem1delta null mutants are
      defective in G1 arrest and transcriptional activation in response to mating
      pheromone. Bem1 protein stimulates Fus3 (MAPK) activity and associates with Ste5,
      the tethering protein essential for activation of the MAPK kinase kinase Ste11.
      Bem1-Ste5 complexes also contain Ste11, Ste7 (MAPK kinase), and Fus3, suggesting
      that Ste5 localizes the MAPK cascade to Bem1. Strikingly, Bem1 also copurifies
      with Far1, a Fus3 substrate required for G1 arrest and proper polarized growth
      during mating. These and other results suggest that Bem1 may cross-link the Ste5
      MAPK cascade complex to upstream activators and specific downstream substrates at
      the shmoo tip, thus enabling efficient circuitry for G1 arrest and mating.

PMID- 8754809
TI  - Oligomerization of the ABL tyrosine kinase by the Ets protein TEL in human
      leukemia.
AB  - TEL is a member of the Ets family of transcription factors which are frequently
      rearranged in human leukemia. The mechanism of TEL-mediated transformation,
      however, is unknown. We report the cloning and characterization of a chromosomal
      translocation associated with acute myeloid leukemia which fuses TEL to the ABL
      tyrosine kinase. The TEL-ABL fusion confers growth factor-independent growth to
      the marine hematopoietic cell line Ba/F3 and transforms Rat-1 fibroblasts and
      primary murine bone marrow cells. TEL-ABL is constitutively tyrosine
      phosphorylated and localizes to the cytoskeleton. A TEL-ABL mutant containing an
      ABL kinase-inactivating mutation is not constitutively phosphorylated and is
      nontransforming but retains cytoskeletal localization. However, constitutive
      phosphorylation, cytoskeletal localization, and transformation are all dependent
      upon a highly conserved region of TEL termed the helix-loop-helix (HLH) domain.
      TEL-ABL formed HLH-dependent homo-oligomers in vitro, a process critical for
      tyrosine kinase activation. These experiments suggest that oligomerization of TEL
      ABL mediated by the TEL HLH domain is required for tyrosine kinase activation,
      cytoskeletal localization, and transformation. These data also suggest that
      oligomerization of Ets proteins through the highly conserved HLH domain may
      represent a previously unrecognized phenomenon.

PMID- 8754810
TI  - Membrane localization of phosphatidylinositol 3-kinase is sufficient to activate
      multiple signal-transducing kinase pathways.
AB  - Phosphatidylinositol (PI) 3-kinase is a cytoplasmic signaling molecule recruited
      to the membrane by activated growth factor receptors. The p85 subunit of PI 3
      kinase links the catalytic p110 subunit to activated growth factor receptors and
      is required for enzymatic activity of p110. In this report, we describe the
      effects of expressing novel forms of p110 that are targeted to the membrane by
      either N-terminal myristoylation or C-terminal farnesylation. The expression of
      membrane-localized p110 is sufficient to trigger downstream responses
      characteristic of growth factor action, including the stimulation of pp70 S6
      kinase, Akt/Rac, and Jun N-terminal kinase (JNK). These responses can also be
      triggered by expression of a form of p110 (p110*) that is cytosolic but exhibits
      a high specific activity. Finally, targeting of pl10* to the membrane results in
      maximal activation of downstream responses. Our data demonstrate that either
      membrane-targeted forms of p110 or a form of p110 with high specific activity can
      act as constitutively active PI 3-kinases and induce PI 3-kinase-dependent
      responses in the absence of growth factor stimulation. The results also show that
      PI 3-kinase activation is sufficient to stimulate several kinases that appear to
      function in different signaling pathways.

PMID- 8754811
TI  - Induction of peroxisome proliferator-activated receptor gamma during the
      conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPbeta,
      C/EBPdelta, and glucocorticoids.
AB  - The differentiation of 3T3 preadipocytes into adipocytes is accompanied by a
      transient induction of C/EBPbeta and C/EBPdelta expression in response to
      treatment of the cells with methylisobutylxanthine (MIX) and dexamethasone (DEX),
      respectively. In this report, we demonstrate that peroxisome proliferator
      activated receptor gamma (PPARgamma) expression in 3T3-L1 preadipocytes is
      induced by MIX and DEX, suggesting that C/EBPbeta and C/EBPdelta may be involved
      in this process. Using a tetracycline-responsive expression system, we have
      recently shown that the conditional ectopic expression of C/EBPbeta in NIH 3T3
      fibroblasts (beta2 cells) in the presence of DEX activates the synthesis of
      peroxisome PPARgamma mRNA. Subsequent exposure of these cells to PPAR activators
      stimulates their conversion into adipocytes; however, neither the expression of
      C/EBPbeta nor exposure to DEX alone is capable of inducing PPARgamma expression
      in the beta2 cell line. We find that unlike the case for 3T3 preadipocytes,
      C/EBPdelta is not induced by DEX in these 3T3 fibroblasts and therefore is not
      relaying the effect of this glucocorticoid to the PPARgamma gene. To define the
      role of glucocorticoids in regulating PPARgamma expression and the possible
      involvement of C/EBPdelta, we have established an additional set of NIH 3T3 cell
      lines expressing either C/EBPdelta alone (delta23 cells) or C/EBPdelta and
      C/EBPbeta together (beta/delta39 cells), using the tetracycline-responsive
      system. Culture of these cells in tetracycline-deficient medium containing DEX,
      MIX, insulin, and fetal bovine serum shows that the beta/delta39 cells express
      PPARgamma and aP2 mRNAs at levels that are almost equivalent to those observed in
      fully differentiated 3T3-L1 adipocytes. These levels are approximately threefold
      higher than their levels of expression in the beta2 cells. Despite the fact that
      these beta/delta39 cells produce abundant amounts of C/EBPbeta and C/EBPdelta (in
      the absence of tetracycline), they still require glucocorticoids to attain
      maximum expression of PPARgamma mRNA. Furthermore, the induction of PPARgamma
      mRNA by exposure of these cells to DEX occurs in the absence of ongoing protein
      synthesis. The delta23 cells, on the other hand, are not capable of activating
      PPARgamma gene expression when exposed to the same adipogenic inducers. Finally,
      attenuation of ectopic C/EBPbeta production at various stages during the
      differentiation process results in a concomitant inhibition of PPARgamma and the
      adipogenic program. These data strongly suggest that the induction of PPARgamma
      gene expression in multipotential mesenchymal stem cells (NIH 3T3 fibroblasts) is
      dependent on elevated levels of C/EBPbeta throughout the differentiation process,
      as well as an initial exposure to glucocorticoids. C/EBPdelta may function by
      synergizing with C/EBPbeta to enhance the level of PPARgamma expression.

PMID- 8754812
TI  - The receptor-DNA complex determines the retinoid response: a mechanism for the
      diversification of the ligand signal.
AB  - To obtain insights into the principles governing the complex biological responses
      to retinoids, we have analyzed the ligand sensitivities of various retinoid
      receptor-DNA complexes. We find that different retinoid receptor heterodimers
      show distinct activation patterns with various response elements while a given
      heterodimer can be activated at different retinoic acid concentrations on
      different response elements. In vitro binding experiments suggest that the same
      retinoic acid receptor-retinoid X receptor (RAR-RXR) heterodimer can have
      different ligand affinities, depending on the response element it is bound to.
      The differential responses of a particular receptor heterodimer with various
      retinoic acid responsive elements can be enhanced through the use of
      conformationally restricted retinoids. RAR- and RXR-selective retinoids can also
      synergistically activate the receptor heterodimers, indicating that both partners
      in the heterodimer can contribute to ligand-induced transcriptional activation.
      However, the relative influence of the RAR or RXR partner is specific for each
      response element. Together, our data demonstrate that it is the receptor-DNA
      complex and not the receptor alone that determines the ligand response. This
      flexibility allows for a highly pleiotropic retinoid response. Furthermore,
      conformationally restricted retinoids can accentuate the differential responses
      and exhibit a certain degree of gene selectivity by differentially activating the
      RAR or RXR component in the context of a given response element.

PMID- 8754813
TI  - YMXM motifs and signaling by an insulin receptor substrate 1 molecule without
      tyrosine phosphorylation sites.
AB  - Tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) by the activated
      receptors for insulin, IGF-1, and various cytokines creates binding sites for
      signaling proteins with Src homology 2 domains (SH2 proteins). Determining the
      role of specific SH2 proteins during insulin signaling has been difficult because
      IRS-1 possesses as many as 18 potential tyrosine phosphorylation sites, several
      of which contain redundant motifs. Using 32D cells, which contain no endogenous
      IRS proteins, we compared the signaling ability of an IRS-1 molecule in which 18
      potential tyrosine phosphorylation sites were replaced by phenylalanine (IRS
      1(F18)) with two derivative molecules which retained three YMXM motifs (IRS
      1(3YMXM)) or the two COOH-terminal SHP2-Fyn binding sites (IRS-1(YCT)). During
      insulin stimulation, IRS-1(F18) failed to undergo tyrosine phosphorylation or
      mediate activation of the phosphotidylinositol (PI) 3'-kinase or p70(s6k); IRS
      1(YCT) was tyrosine phosphorylated but also failed to mediate these signaling
      events. Neither IRS-1(3YMXM) nor IRS-1(YCT) mediated activation of mitogen
      activated protein kinases. IRS-1(F18) and IRS-1(YCT) partially mediated similar
      levels of insulin-stimulated mitogenesis at high insulin concentrations, however,
      suggesting that IRS-1 contains phosphotyrosine-independent elements which effect
      mitogenic signals, and that the sites in IRS-l(YCT) do not augment this signal.
      IRS-1(3YMXM) mediated the maximal mitogenic response to insulin, although the
      response to insulin was more sensitive with wild-type IRS-1. By contrast, the
      association of IRS-1(3YMXM) with PI 3'-kinase was more sensitive to insulin than
      the association with IRS-1. Thus, the binding of SH2 proteins (such as PI 3'
      kinase) by YMXM motifs in IRS-1 is an important element in the mitogenic
      response, but other elements are essential for full mitogenic sensitivity.

PMID- 8754814
TI  - Overexpression of an activated rasG gene during growth blocks the initiation of
      Dictyostelium development.
AB  - Transformants that expressed either the wild-type rasG gene, an activated rasG
      G12T gene, or a dominant negative rasG-S17N gene, all under the control of the
      folate-repressible discoidin (dis1gamma) promoter, were isolated. All three
      transformants expressed high levels of Ras protein which were reduced by growth
      in the presence of folate. All three transformants grew slowly, and the reduction
      in growth rate correlated with the amount of RasG protein produced, suggesting
      that RasG is important in regulating cell growth. The pVEII-rasG transformant
      containing the wild-type rasG gene developed normally despite the presence of
      high levels of RasG throughout development. This result indicates that the down
      regulation of rasG that normally occurs during aggregation of wild-type strains
      is not essential for the differentiation process. Dictyostelium transformants
      expressing the dominant negative rasG-S17N gene also differentiated normally.
      Dictyostelium transformants that overexpressed the activated rasG-G12T gene did
      not aggregate. The defect occurred very early in development, since the
      expression of car1 and pde, genes that are normally induced soon after the
      initiation of development, was repressed. However, when the transformant cells
      were pulsed with cyclic AMP, expression of both genes returned to wild-type
      levels. The transformants exhibited chemotaxis to cyclic AMP, and development was
      synergized by mixing with wild-type cells. Furthermore, cells that were pulsed
      with cyclic AMP for 4 h before being induced to differentiate by plating on
      filters produced small, but otherwise normal, fruiting bodies. These results
      suggest that the rasG-G12T transformants are defective in cyclic AMP production
      and that RasG - GTP blocks development by interfering with the initial generation
      of cyclic AMP pulses.

PMID- 8754815
TI  - DNA binding domain and subunit interactions of transcription factor IIIC revealed
      by dissection with poliovirus 3C protease.
AB  - Transcription factor IIIC (TFIIIC) is a general RNA polymerase III transcription
      factor that binds the B-box internal promotor element of tRNA genes and the
      complex of TFIIIA with a 5S rRNA gene. TFIIIC then directs the binding of TFIIIB
      to DNA upstream of the transcription start site. TFIIIB in turn directs RNA
      polymerase III binding and initiation. Human TFIIIC contains five different
      subunits. The 243-kDa alpha subunit can be specifically cross-linked to B-box
      DNA, but its sequence does not reveal a known DNA binding domain. During
      poliovirus infection, TFIIIC is cleaved and inactivated by the poliovirus-encoded
      3C protease (3Cpro). Here we analyzed the cleavage of TFIIIC subunits by 3Cpro in
      vitro and during poliovirus infection of HeLa cells. Analyses of the DNA binding
      activities of the resulting subcomplexes indicated that an N-terminal 83-kDa
      domain of the alpha subunit associates with the beta subunit to generate the
      TFIIIC DNA binding domain. Cleavage with 3Cpro also generated an approximately
      125-kDa C-terminal fragment of the alpha subunit which remained associated with
      the gamma and epsilon subunits.

PMID- 8754817
TI  - per mRNA cycling is locked to lights-off under photoperiodic conditions that
      support circadian feedback loop function.
AB  - Circadian fluctuations in per mRNA and protein are central to the operation of a
      negative feedback loop that is necessary for setting the free-running period and
      for entraining the circadian oscillator to light-dark cycles. In this study, per
      mRNA cycling and locomotor activity rhythms were measured under different light
      and dark cycling regimes to determine how photoperiods affect the molecular
      feedback loop and circadian behavior, respectively. These experiments reveal that
      per mRNA peaks in abundance 4 h after lights-off in photoperiods of < or = 16 h,
      that, phase shifts in per mRNA cycling and behavioral rhythmicity occur rapidly
      after flies are transferred from one photoperiod to another, and that
      photoperiods longer than 20 h abolish locomotor activity rhythms and leave per
      mRNA at a median constitutive level. These results indicate that the per feedback
      loop uses lights-off as a phase reference point and suggest (along with previous
      findings for per01 and tim01) that per mRNA cycling is not regulated via simple
      negative feedback from the per protein.

PMID- 8754816
TI  - Interaction of the interferon-induced PKR protein kinase with inhibitory proteins
      P58IPK and vaccinia virus K3L is mediated by unique domains: implications for
      kinase regulation.
AB  - Expression of the double-stranded RNA-activated protein kinase (PKR) is induced
      by interferons, with PKR activity playing a pivotal role in establishing the
      interferon-induced antiviral and antiproliferative states. PKR is directly
      regulated by physical association with the specific inhibitor, P58IPK, a cellular
      protein of the tetratricopeptide repeat (TPR) family, and K3L, the product of the
      corresponding vaccinia virus gene. P58IPK and K3L repress PKR activation and
      activity. To investigate the mechanism of P58IPK- and K3L-mediated PKR
      inhibition, we have used a combination of in vitro and in vivo binding assays to
      identify the interactive regions of these proteins. The P58IPK-interacting site
      of PKR was mapped to a 52-amino-acid aa segment (aa 244 to 296) spanning the ATP
      binding region of the protein kinase catalytic domain. The interaction with PKR
      did not require the C-terminal DNA-J homology region of P58IPK but was dependent
      on the presence of the eukaryotic initiation factor 2-alpha homology region,
      mapping to the 34 aa within the sixth P58IPK TPR motif. Consistent with other TPR
      proteins, P58IPK formed multimers in vivo: the N-terminal 166 aa were both
      necessary and sufficient for complex formation. A parallel in vivo analysis to
      map the K3L-binding region of PKR revealed that like P58IPK , K3L interacted
      exclusively with the PKR protein kinase catalytic domain. In contrast, however,
      the K3L-binding region of PKR was localized to within aa 367 to 551,
      demonstrating that each inhibitor bound PKR in unique, nonoverlapping domains.
      These data, taken together, suggest that P58IPK and K3L may mediate PKR
      inhibition by distinct mechanisms. Finally, we will propose a model of PKR
      inhibition in which P58IPK or a P58IPK complex binds PKR and interferes with
      nucleotide binding and autoregulation, while formation of a PKR-K3L complex
      interferes with active-site function and/or substrate association.

PMID- 8754818
TI  - Mutations in two Ku homologs define a DNA end-joining repair pathway in
      Saccharomyces cerevisiae.
AB  - DNA double-strand break (DSB) repair in mammalian cells is dependent on the Ku
      DNA binding protein complex. However, the mechanism of Ku-mediated repair is not
      understood. We discovered a Saccharomyces cerevisiae gene (KU80) that is
      structurally similar to the 80-kDa mammalian Ku subunit. Ku8O associates with the
      product of the HDF1 gene, forming the major DNA end-binding complex of yeast
      cells. DNA end binding was absent in ku80delta, hdf1delta, or ku80delta hdf1delta
      strains. Antisera specific for epitope tags on Ku80 and Hdf1 were used in
      supershift and immunodepletion experiments to show that both proteins are
      directly involved in DNA end binding. In vivo, the efficiency of two DNA end
      joining processes were reduced >10-fold in ku8Odelta, hdfldelta, or ku80delta
      hdf1delta strains: repair of linear plasmid DNA and repair of an HO endonuclease
      induced chromosomal DSB. These DNA-joining defects correlated with DNA damage
      sensitivity, because ku80delta and hdf1delta strains were also sensitive to
      methylmethane sulfonate (MMS). Ku-dependent repair is distinct from homologous
      recombination, because deletion of KU80 and HDF1 increased the MMS sensitivity of
      rad52delta. Interestingly, rad5Odelta, also shown here to be defective in end
      joining, was epistatic with Ku mutations for MMS repair and end joining.
      Therefore, Ku and Rad50 participate in an end-joining pathway that is distinct
      from homologous recombinational repair. Yeast DNA end joining is functionally
      analogous to DSB repair and V(D)J recombination in mammalian cells.

PMID- 8754820
TI  - Protein sequence requirements for function of the human T-cell leukemia virus
      type 1 Rex nuclear export signal delineated by a novel in vivo randomization
      selection assay.
AB  - The Rex protein of human T-cell leukemia virus type 1, like the functionally
      equivalent Rev protein of human immunodeficiency virus type 1, contains a leucine
      rich activation domain that specifically interacts with the human nucleoporin
      like Rab/hRIP cofactor. Here, this Rex sequence is shown to function also as a
      protein nuclear export signal (NES). Rex sequence libraries containing randomized
      forms of the activation domain/NES were screened for retention of the ability to
      bind Rab/hRIP by using the yeast two-hybrid assay. While the selected sequences
      differed widely in primary sequence, all were functional as Rex activation
      domains. In contrast, randomized sequences that failed to bind Rab/hRIP lacked
      Rex activity. The selected sequences included one with homology to the Rev
      activation domain/NES and a second that was similar to the NES found in the
      cellular protein kinase inhibitor alpha. A highly variant, yet fully active,
      activation domain sequence selected on the basis of Rab/hRIP binding retained
      full NES function even though this sequence preserved only a single leucine
      residue. In contrast, nonfunctional activation domain mutants that were unable to
      bind Rab/hRIP had also lost NES function. These data demonstrate that NES
      activity is a defining characteristic of the activation domains found in the
      Rev/Rex class of retroviral regulatory proteins and strongly support the
      hypothesis that the Rab/hRIP cofactor plays a critical role in mediating the
      biological activity of these NESs. In addition, these data suggest a consensus
      sequence for NESs of the Rev/Rex class.

PMID- 8754819
TI  - Protein phosphatase type 1 interacts with proteins required for meiosis and other
      cellular processes in Saccharomyces cerevisiae.
AB  - Protein phosphatase type I (PP1) is involved in diverse cellular processes, and
      its activity toward specific substrates is thought to be controlled by different
      regulatory or targeting subunits. To identify regulatory subunits and substrates
      of the Saccharomyces cerevisiae PP1, encoded by GLC7, we used the two-hybrid
      system to detect interacting proteins. Among the many proteins identified were
      Gac1, a known glycogen regulatory subunit, and a protein with homology to Gac1.
      We also characterized a new gene designated GIP1, for Glc7-interacting protein.
      We show that a Gip1 fusion protein coimmunoprecipitates with PP1 from cell
      extracts. Molecular and genetic analyses indicate that GIP1 is expressed
      specifically during meiosis, affects transcription of late meiotic genes, and is
      essential for sporulation. Thus, the Gip1 protein is a candidate for a meiosis
      specific substrate or regulator of PP1. Finally, we recovered two genes, RED1 and
      SCD5, with roles in meiosis and the vesicular secretory pathway, respectively.
      These results provide strong evidence implicating PP1 function in meiosis. In
      addition, this study indicates that the two-hybrid system offers a promising
      approach to understanding the multiple roles and interactions of PP1 in cellular
      regulation.

PMID- 8754821
TI  - SIN3-dependent transcriptional repression by interaction with the Mad1 DNA
      binding protein.
AB  - The SIN3 gene in Saccharomyces cerevisiae encodes a negative regulator of
      transcription of a large number of genes. Mouse homologs of SIN3 have been
      identified through screens for proteins interacting with the mammalian Mad1
      protein, a transcriptional repressor. We find that yeast Sin3 (ySin3) interacts
      with Madl and that, as for mouse Sin3, the N terminus of Mad1 interacts with the
      PAH2 domain of ySin3. Although Mad1 (a basic helix-loop-helix leucine zipper
      [bHLH-Zip) protein) forms a heterodimer with the Max bHLH-Zip protein, LexA-Mad1
      and VP16-Max do not activate transcription of a reporter gene in a two-hybrid
      assay. This failure in activation is due to direct repression by ySin3, as LexA
      Mad1 and VP16-Max are able to activate the two-hybrid reporter in a sin3 mutant.
      This inhibition of activation by LexA-Mad1 and VP16-Max requires the PAH2 domain
      of ySin3 and the N-terminal interaction region of Mad1. These data demonstrate
      that ySin3 functions as a transcriptional repressor by being brought to promoters
      by interacting with proteins bound to DNA.

PMID- 8754822
TI  - att, a target for regulation by tra2 in the testes of Drosophila melanogaster,
      encodes alternative RNAs and alternative proteins.
AB  - We have identified a gene, alternative testis transcripts (att), which is
      alternatively expressed, at both the RNA and protein levels, in testes and
      somatic tissues. The testis-specific RNA differs from somatic RNAs in both
      promoter usage and RNA processing and is dependent on the function of the
      transformer 2 gene. The differences between the somatic and testis RNAs have
      substantial consequences at the protein level. The somatic RNAs encode a protein
      with homology to the mammalian Graves' disease carrier proteins. The testis RNA
      lacks the initiation codons used in somatic tissue and encodes two different
      proteins. One of these begins in a testis-specific exon, uses a reading frame
      different from that for the somatic protein, and is completely novel. The other
      protein initiates translation in the frame of the somatic RNA at a Len CUG codon
      which is within the open reading frame for the somatic protein. This produces a
      novel truncated version of the Graves' disease carrier protein-like protein that
      lacks all sequences N terminal to the first transmembrane domain.

PMID- 8754824
TI  - Developmental-stage-specific expression and regulation of an amphotropic
      retroviral receptor in hematopoietic cells.
AB  - Expression of the transmembrane receptor protein Ram-1 may be critical to
      optimizing retroviral gene transfer. Ram-1 acts as both a sodium-dependent
      phosphate transporter and a receptor for amphotropic retroviruses. We previously
      reported detectable Ram-1 in murine hematopoietic fetal liver cells (FLC) despite
      resistance of these cells to amphotropic retroviral transduction (infection). We
      document here that Ram-1 expression is completely absent in murine yolk sac cells
      from days 9.5 through 13.5 of ontogeny and first appears at low levels in
      midgestational FLC between days 13.5 and 14.5. In addition, Ram-1 expression is
      detected only in more differentiated populations within FLC, day 14.5, and not in
      those highly enriched for stem cells, indicating developmental regulation of Ram
      1 during murine hematopoiesis. Others have reported the in vitro use of phosphate
      free medium as a stimulus to increase levels of Ram-1 mRNA in nonhematopoietic
      cells. We now demonstrate that Ram-1 poly(A)+ mRNA increases significantly
      following culture of FLC in phosphate-free medium. Further, transduction of FLC
      in phosphate-free medium with an amphotropic retrovirus containing the multiple
      drug resistance gene leads to gene transfer not observed previously. These data
      demonstrate that (i) the normal resistance of FLC to amphotropic transduction is
      most likely due to an insufficient number of Ram-1 molecules for efficient
      retroviral recognition and binding, and (ii) Ram-1 can be upregulated by
      increasing the need for phosphate transport across the cell membrane.

PMID- 8754823
TI  - Involvement of the transcription factor NF-kappaB in tubular morphogenesis of
      human microvascular endothelial cells by oxidative stress.
AB  - Oxygen radicals are induced under various pathologic conditions associated with
      neovascularization. Oxygen radicals modulate angiogenesis in cultured human
      microvascular endothelial cells by an unknown mechanism. Treatment of human
      microvascular endothelial cells for 15 min with 0.1 to 0.5 mM hydrogen peroxide
      (H2O2) or 100 U of tumor necrosis factor alpha per ml induced tubular
      morphogenesis in type I collagen gels. Gel shift assays with nuclear extracts
      demonstrated that H2O2 increases the binding activities of two transcription
      factors, NF-kappaB and AP-1, but not of Spl. Tumor necrosis factor alpha
      increased the binding activities of all three factors. A supershift assay with
      specific antibodies against JunB, JunD, and c-Jun (Jun family) showed that the
      antibody against c-Jun supershifted the AP-1 complex after H2O2 treatment.
      Coadministration of the antisense sequence of NF-kappaB inhibited H2O2-dependent
      tubular morphogenesis, and the antisense c-Jun oligonucleotide caused partial
      inhibition. The angiogenic factor responsible for H2O2-induced tubular
      morphogenesis was examined. Cellular mRNA levels of vascular endothelial growth
      factor and interleukin-8 (IL-8), but not those of transforming growth factor
      alpha, were increased after treatment with 0.5 mM H2O2. Coadministration of anti
      IL-8 antibody inhibited tubular morphogenesis enhanced by H2O2, and IL-8 itself
      also enhanced the formation of tube-like structures. Treatment with antisense NF
      kappaB oligonucleotide completely blocked H2O2-dependent IL-8 production by
      endothelial cells. The tubular morphogenesis of vascular endothelial cells after
      treatment with oxidative stimuli and its possible association with NF-kappaB and
      IL-8, is examined.

PMID- 8754825
TI  - The A1 x U72 base pair conserved in eukaryotic initiator tRNAs is important
      specifically for binding to the eukaryotic translation initiation factor eIF2.
AB  - The formation of a specific ternary complex between eukaryotic initiation factor
      2 (eIF2), the initiator methionyl-tRNA (Met-tRNA), and GTP is a critical step in
      translation initiation in the cytoplasmic protein-synthesizing system of
      eukaryotes. We show that the A1 x U72 base pair conserved at the end of the
      acceptor stem in eukaryotic and archaebacterial initiator methionine tRNAs plays
      an important role in this interaction. We changed the A1 x U72 base pair of the
      human initiator tRNA to G1 x C72 and expressed the wild-type and mutant tRNA
      genes in the yeast Saccharomyces cerevisiae by using constructs previously
      developed in our laboratory for expression of the human initiator tRNA gene in
      yeasts. We show that both the wild-type and mutant human initiator tRNAs are
      aminoacylated well in vivo. We have isolated the wild-type and mutant human
      initiator tRNAs in substantially pure form, free of the yeast initiator tRNA, and
      have analyzed their properties in vitro. The G1 x C72 mutation affects
      specifically the binding affinity of eIF2 for the initiator tRNA. It has no
      effect on the subsequent formation of 40S or 80S ribosome initiator Met-tRNA-AUG
      initiation complexes in vitro or on the puromycin reactivity of the Met-tRNA in
      the 80S initiation complex.

PMID- 8754826
TI  - Transcriptional induction of the alpha-1 acid glycoprotein (AGP) gene by
      synergistic interaction of two alternative activator forms of AGP/enhancer
      binding protein (C/EBP beta) and NF-kappaB or Nopp140.
AB  - Alpha-1 acid glycoprotein/enhancer-binding protein (AGP/EBP) (C/EBPbeta), a
      member of the C/EBP family, is one of the key transcription factors responsible
      for the induction of a wide array of genes, some of which are expressed during
      the acute-phase response. Both activator and repressor were shown to be encoded
      by the intronless agp/ebp or its rat and human homologs, which contain a common
      bZIP domain at their C-terminal regions. Expression of the AGP gene (agp) is
      regulated by AGP/EBP in liver during the acute-phase response. However, the
      molecular mechanism for this regulation is poorly understood. The experiments
      reported here demonstrate that two activator forms of AGP/EBP, one of which has
      an additional 21 amino acids at its N-terminal region, are expressed in liver as
      well as in a number of cell lines. We have also demonstrated that NF-kappaB and a
      phosphoprotein of 140 kDa, Nopp140, interact with different AGP/EBP activators
      synergistically, which results in induction of the agp gene in an AGP/EBP-binding
      motif-dependent manner. Furthermore, extracellular stimuli that are known to be
      NF-kappaB inducers can selectively activate the agp gene by cooperating with one
      of the two activator forms of AGP/EBP. The physiological significance of
      differential regulation for the function of two activator forms of AGP/EBP
      through selective interaction with different transcription factors is discussed.

PMID- 8754827
TI  - The human clotting factor VIII cDNA contains an autonomously replicating sequence
      consensus- and matrix attachment region-like sequence that binds a nuclear
      factor, represses heterologous gene expression, and mediates the transcriptional
      effects of sodium butyrate.
AB  - Expression of the human blood-clotting factor VIII (FVIII) cDNA is hampered by
      the presence of sequences located in the coding region that repress
      transcription. We have previously identified a 305-bp fragment within the FVIII
      cDNA that is involved in the repression (R.C. Hoeben, F.J. Fallaux, S.J. Cramer,
      D.J.M. van den Wollenberg, H. van Ormondt, E. Briet, and A.J. van der Eb, Blood
      85:2447-2454, 1995). Here, we show that this 305-bp region of FVIII cDNA contains
      sequences that resemble the yeast (Saccharomyces cerevisiae) autonomously
      replicating sequence consensus. Two of these DNA elements coincide with AT-rich
      sequences that are often found in matrix attachment regions or scaffold-attached
      regions. One of these elements, consisting of nucleotides 1569 to 1600 of the
      FVIII cDNA (nucleotide numbering is according to the system of Wood et al. (W.I.
      Wood, D.J. Capon, C.C. Simonsen, D.L. Eaton, J. Gitschier, D. Keyt, P.H. Seeburg,
      D.H. Smith, P. Hollingshead, K.L. Wion, et al., Nature [London] 312:330
      337,1984), binds a nuclear factor in vitro but loses this capacity after four of
      its base pairs have been changed. A synthetic heptamer of this segment can
      repress the expression of a chloramphenicol acetyltransferase (CAT) reporter gene
      and also loses this capacity upon mutation. Furthermore, we demonstrate that
      repression by FVIII sequences can be relieved by sodium butyrate. We demonstrate
      that the synthetic heptamer (FVIII nucleotides 1569 to 1600), when placed
      upstream of the Moloney murine leukemia virus long terminal repeat promoter that
      drives the CAT reporter, can render the CAT reporter inducible by butyrate. This
      effect was absent when the same element was mutated. The stimulatory effect of
      butyrate could not be attributed to butyrate-responsive elements in the studied
      long terminal repeat promoters. Our data provide a functional characterization of
      the sequences that repress expression of the FVIII cDNA. These data also suggest
      a link between transcriptional repression by FVIII cDNA elements and the
      stimulatory effect of butyrate on FVIII cDNA expression.

PMID- 8754828
TI  - Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein
      (CHOP/GADD153).
AB  - The gene encoding C/EBP-homologous protein (CHOP), also known as growth arrest
      and DNA-damage-inducible gene 153 (GADD153), is activated by agents that
      adversely affect the function of the endoplasmic reticulum (ER). Because of the
      pleiotropic effects of such agents on other cellular processes, the role of ER
      stress in inducing CHOP gene expression has remained unclear. We find that cells
      with conditional (temperature-sensitive) defects in protein glycosylation (CHO
      K12 and BHK tsBN7) induce CHOP when cultured at the nonpermissive temperature. In
      addition, cells that are defective in initiating the ER stress response, because
      of overexpression of an exogenous ER chaperone, BiP/GRP78, exhibit attenuated
      inducibility of CHOP. Surprisingly, attenuated induction of CHOP was also noted
      in BiP-overexpressing cells treated with methyl methanesulfonate, an agent
      thought to activate CHOP by causing DNA damage. The roles of DNA damage and
      growth arrest in the induction of CHOP were therefore reexamined. Induction of
      growth arrest by culture to confluence or treatment with the enzymatic inhibitor
      N-(phosphonacetyl)-L-aspartate did not induce CHOP. Furthermore, both a DNA
      damage-causing nucleoside analog (5-hydroxymethyl-2'-deoxyuridine) and UV light
      alone did not induce CHOP. These results suggest that CHOP is more responsive to
      ER stress than to growth arrest or DNA damage and indicate a potential role for
      CHOP in linking stress in the ER to alterations in gene expression.

PMID- 8754829
TI  - SUM1-1, a dominant suppressor of SIR mutations in Saccharomyces cerevisiae,
      increases transcriptional silencing at telomeres and HM mating-type loci and
      decreases chromosome stability.
AB  - Transcriptional silencing in the yeast Saccharomyces cerevisiae occurs at HML and
      HMR mating-type loci and telomeres and requires the products of the silent
      information regulator (SIR) genes. Recent evidence suggests that the silencer-
      and telomere-binding protein Rap1p initiates silencing by recruiting a complex of
      Sir proteins to the chromosome, where they act in some way to modify chromatin
      structure or accessibility. A single allele of the SUM1gene (SUM1-1) which
      restores silencing at HM loci in strains mutant for any of the four SIR genes was
      identified a number of years ago. However, conflicting genetic results and the
      lack of other alleles of SUM1 made it difficult to surmise the wild-type function
      of SUM1 or the manner in which the SUM1-1 mutation restores silencing in sir
      mutant strains. Here we report the cloning and characterization of the SUM1 gene
      and the SUM1-1 mutant allele. Our results indicate that SUM1-1 is an unusual
      altered-function mutation that can bypass the need for SIR function in HM
      silencing and increase repression at telomeres. A sum1 deletion mutation has only
      minor effects on silencing in SIR strains and does not restore silencing in sir
      mutants. In addition to its effect on transcriptional silencing, the SUM1-1
      mutation (but not a sum1 deletion) increases the rate of chromosome loss and cell
      death. We suggest several speculative models for the action of SUM1-1 in
      silencing based on these and other data.

PMID- 8754831
TI  - Essential and nonessential histone H2A variants in Tetrahymena thermophila.
AB  - Although variants have been identified for every class of histone, their
      functions remain unknown. We have been studying the histone H2A variant hv1 in
      the ciliated protozoan Tetrahymena thermophila. Sequence analysis indicates that
      hv1 belongs to the H2A.F/Z type of histone variants. On the basis of the high
      degree of evolutionary conservation of this class of histones, they are proposed
      to have one or more distinct and essential functions that cannot be performed by
      their major H2A counterparts. Considerable evidence supports the hypothesis that
      the hv1 protein in T. thermophila and hv1-like proteins in other eukaryotes are
      associated with active chromatin. In T. thermophila, simple mass transformation
      and gene replacement techniques have recently become available. In this report,
      we demonstrate that either the HTA1 gene or the HTA2 gene, encoding the major
      H2As, can be completely replaced by disrupted genes in the polyploid,
      transcriptionally active macronucleus, indicating that neither of the two genes
      is essential. However, only some of the HTA3 genes encoding hv1 can be replaced
      by disrupted genes, indicating that the H2A.F/Z type variants have an essential
      function that cannot be performed by the major H2A genes. Thus, an essential gene
      in T. thermophila can be defined by the fact that it can be partially, but not
      completely, eliminated from the polyploid macronucleus. To our knowledge, this
      study represents the first use of gene disruption technology to study core
      histone gene function in any organism other than yeast and the first
      demonstration of an essential gene in T. thermophila using these methods. When a
      rescuing plasmid carrying a wild-type HTA3 gene was introduced into the T.
      thermophila cells, the endogenous chromosomal HTA3 could be completely replaced,
      defining a gene replacement strategy that can be used to analyze the function of
      essential genes.

PMID- 8754830
TI  - Functional interaction between p53, the TATA-binding protein (TBP), andTBP
      associated factors in vivo.
AB  - The transcriptional activator p53 is known to interact with components of the
      general transcription factor TFIID in vitro. To examine the relevance of these
      associations to transcriptional activation in vivo, plasmids expressing a p53
      GAL4 chimera and Drosophila TATA-binding protein (dTBP) were transfected into
      Drosophila Schneider cells. p53-GAL4 and dTBP displayed a markedly synergistic
      effect on activated transcription from a GAL4 site-containing reporter that was
      at least 10-fold greater than observed with other activators tested. A mutant p53
      previously shown to be defective in both transcriptional activation in vivo and
      in binding to TBP-associated factors (TAFs) in vitro, although still capable of
      binding dTBP, did not cooperate with dTBP, suggesting that TAFs may contribute to
      this synergy. Providing further support for this possibility, transfected dTBP
      assembled into rapidly sedimenting complexes and could be immunoprecipitated with
      anti-TAF antibodies. While overexpression of any of several TAFs did not affect
      basal transcription, in either the presence or the absence of cotransfected dTBP,
      overexpression of TAFII230 inhibited transcriptional activation mediated by p53
      GAL4 as well as by GAL4-VP16 and Sp1. Overexpression of TAFII40 and TAFII60 also
      inhibited activation by p53-GAL4 but had negligible effects on activation by GAL4
      VP16 and Sp1, while TAFII110 did not affect any of the activators. TAF-mediated
      inhibition of activated transcription could be rescued by high levels of
      exogenous dTBP, which also restored full synergy. These data demonstrate for the
      first time that functional interactions can occur in vivo between TBP, TAFs, and
      p53.

PMID- 8754832
TI  - Adenovirus E1A downregulates cJun- and JunB-mediated transcription by targeting
      their coactivator p300.
AB  - Transcription factors and cofactors play critical roles in cell growth and
      differentiation. Alterations of their activities either through genetic mutations
      or by viral oncoproteins often result in aberrant cell growth and tumorigenesis.
      The transcriptional cofactor p300 has recently been shown to be complexed with
      transcription factors YY1 and CREB. Adenovirus E1A oncoproteins target these
      transcription complexes via physical interactions with p300, resulting in
      alterations of transcription mediated by these transcription factors. Here we
      show that p300 is also critical for repression by E1A of the activities of cJun
      and JunB, two members of the AP-1 transcriptional complexes. This repressive
      effect of E1A is dependent on the p300-binding domain of E1A and can be relieved
      by overexpression of p300. These results suggest that p300 serves as a mediator
      protein for downregulation of AP-1 activity by E1A. This hypothesis was further
      supported by the following observations: (i) in the absence of E1A,
      overexpression of p300 stimulated transcription both through an AP-1 site present
      in the collagenase promoter and through Jun proteins in GAL4 fusion protein-based
      assays; and (ii) overexpression of a mutant p300 lacking the E1A-interacting
      domain reduced the responsiveness of Jun-dependent transcription to E1A
      repression. As predicted from the functional results, p300 physically interacted
      with the Jun proteins. These findings thus established that p300 is a cofactor
      for cJun and JunB. We propose that p300 is a common mediator protein through
      which E1A gains control over multiple transcriptional regulatory pathways in the
      host cells.

PMID- 8754833
TI  - Repression of p27kip1 synthesis by platelet-derived growth factor in BALB/c 3T3
      cells.
AB  - We have investigated the regulation of p27kip1, a cyclin-dependent kinase
      inhibitor, in BALB/c 3T3 cells during growth factor-stimulated transition from
      quiescence (G0) to a proliferative (G1) state. The level of p27kip1 protein falls
      dramatically after mitogenic stimulation and is accompanied by a decrease in
      cyclin E associated p27kip1, as well as a transient increase in cyclin D1
      associated p27kip1 that later declines concomitantly with the loss of total
      p27kip1. Analysis of metabolically labelled cells revealed that cyclin D2, cyclin
      D3, and cdk4 were also partnered with p27kip1 in quiescent BALB/c 3T3 cells and
      that this association decreased after platelet-derived growth factor (PDGF)
      treatment. Furthermore, the decline in p27kip1 and reduced association with
      cyclin D3, initiated by the addition of PDGF but not plasma-derived factors,
      suggested that these changes are involved in competence, the first step in the
      exit from G0. Synthesis of p27kip1 as determined by incorporation of
      [35S]methionine was repressed upon mitogenic stimulation, and PDGF was sufficient
      to elicit this repression within 2 to 3 h. Pulse-chase experiments demonstrated
      the reduced rate of synthesis was not the result of an increased rate of
      degradation. Full repression of p27kip1 synthesis required the continued presence
      of PDGF and failed to occur in the presence of the RNA polymerase inhibitor 5,6
      dichlorobenzimidazole riboside. These characteristics demonstrate that repression
      was a late effect of PDGF and was consistent with our finding that conditional
      expression of activated H-ras did not affect synthesis of p27kip1. Northern (RNA)
      analysis of p27kip1 mRNA revealed that the repression was not accompanied by a
      corresponding decrease in p27kip1 mRNA, suggesting that the PDGF-regulated
      decrease in p27kip1 expression occurred through a translational mechanism.

PMID- 8754834
TI  - Isolation of a novel retinoic acid-responsive gene by selection of genomic
      fragments derived from CpG-island-enriched DNA.
AB  - One of the primary goals in transcription factor research is the elucidation of
      the genetic networks controlled by a factor or by members of a family of closely
      related factors. The pleiotropic effects of retinoic acid (PA) in the developing
      and adult animal are mediated by ligand-inducible transcription factors (RA
      receptors [RARs] and retinoid X receptors [RXRs]) that belong to the superfamily
      of nuclear receptors. Regulatory regions of PA effector genes contain RAR and RXR
      binding sites (RAR elements [RAREs] and RXR elements [RXREs]) that generally
      consist of direct or everted repeats of the core half-site motif, (A/G)G(G/T)TCA.
      In order to identify novel genes regulated by RA, we devised a selection strategy
      based on the premise that regulatory regions of a large number of housekeeping
      and tissue-specific genes are embodied within CpG island DNA. In this method,
      referred to as CpG-selected and amplified binding, fragments derived from the CpG
      island fraction of the murine genome are selected by a gel mobility shift assay
      using in vitro-transcribed and -translated RXR-RAR. Multiple rounds of selection
      coupled with amplification of the fragments by PCR enabled us to clone a
      population of CG-rich fragments of which approximately one-fifth contained
      consensus RAREs or RXREs. Twelve genomic fragments containing novel response
      elements are described, and the transcription unit associated with one of them,
      NN-84AG, was characterized in detail. The mouse NN-84AG transcript is upregulated
      by RA in F9 embryonal carcinoma cells and is homologous to an expressed sequence
      tag (EST41159) derived from a human infant brain cDNA library. Cloning of the
      murine NN8-4AG genomic sequence places the RXRE in the proximity of the
      transcription initiation sites of the gene. Although sequence analysis indicates
      that the EST41159 gene product is novel, a region of amino acid identity with
      sequences of a yeast polypeptide of, as yet, unknown function and the Drosophila
      trithorax protein suggests the presence of an evolutionarily and functionally
      conserved domain. Our study demonstrates that transcription factor binding sites
      and corresponding regulated genes can be identified by selecting fragments
      derived from the CpG island fraction of the genome.

PMID- 8754835
TI  - Efficient transcriptional silencing in Saccharomyces cerevisiae requires a
      heterochromatin histone acetylation pattern.
AB  - Heterochromatin in metazoans induces transcriptional silencing, as exemplified by
      position effect variegation in Drosophila melanogaster and X-chromosome
      inactivation in mammals. Heterochromatic DNA is packaged in nucleosomes that are
      distinct in their acetylation pattern from those present in euchromatin, although
      the role these differences play in the structure of heterochromatin or in the
      effects of heterochromatin on transcriptional activity is unclear. Here we report
      that, as observed in the facultative heterochromatin of the inactive X chromosome
      in female mammalian cells, histones H3 and H4 in chromatin spanning the
      transcriptionally silenced mating-type cassettes of the yeast Saccharomyces
      cerevisiae are hypoacetylated relative to histones H3 and H4 of transcriptionally
      active regions of the genome. By immunoprecipitation of chromatin fragments with
      antibodies specific for H4 acetylated at particular lysine residues, we found
      that only three of the four lysine residues in the amino-terminal domain of
      histone H4 spanning the silent cassettes are hypoacetylated. Lysine 12 shows
      significant acetylation levels. This is identical to the pattern of histone H4
      acetylation observed in centric heterochromatin of D. melanogaster. These two
      observations provide additional evidence that the silent cassettes are
      encompassed in the yeast equivalent of metazoan heterochromatin. Further,
      mutational analysis of the amino-terminal domain of histone H4 in S. cerevisiae
      demonstrated that this observed pattern of histone H4 acetylation is required for
      transcriptional silencing. This result, in conjunction with prior mutational
      analyses of yeast histones H3 and H4, indicates that the particular pattern of
      nucleosome acetylation found in heterochromatin is required for its effects on
      transcription and is not simply a side effect of heterochromatin formation.

PMID- 8754836
TI  - Pho85p, a cyclin-dependent protein kinase, and the Snf1p protein kinase act
      antagonistically to control glycogen accumulation in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, nutrient levels control multiple cellular processes.
      Cells lacking the SNF1 gene cannot express glucose-repressible genes and do not
      accumulate the storage polysaccharide glycogen. The impaired glycogen synthesis
      is due to maintenance of glycogen synthase in a hyperphosphorylated, inactive
      state. In a screen for second site suppressors of the glycogen storage defect of
      snf1 cells, we identified a mutant gene that restored glycogen accumulation and
      which was allelic with PHO85, which encodes a member of the cyclin-dependent
      kinase family. In cells with disrupted PHO85 genes, we observed hyperaccumulation
      of glycogen, activation of glycogen synthase, and impaired glycogen synthase
      kinase activity. In snf1 cells, glycogen synthase kinase activity was elevated.
      Partial purification of glycogen synthase kinase activity from yeast extracts
      resulted in the separation of two fractions by phenyl-Sepharose chromatography,
      both of which phosphorylated and inactivated glycogen synthase. The activity of
      one of these, GPK2, was inhibited by olomoucine, which potently inhibits cyclin
      dependent protein kinases, and contained an approximately 36-kDa species that
      reacted with antibodies to Pho85p. Analysis of Ser-to-Ala mutations at the three
      potential Gsy2p phosphorylation sites in pho85 cells implicated Ser-654 and/or
      Thr-667 in PHO85 control of glycogen synthase. We propose that Pho85p is a
      physiological glycogen synthase kinase, possibly acting downstream of Snf1p.

PMID- 8754837
TI  - A soluble transcription factor, Oct-1, is also found in the insoluble nuclear
      matrix and possesses silencing activity in its alanine-rich domain.
AB  - Expression of the human thyrotropin beta (hTSHbeta) gene is restricted to
      thyrotrophs, at least in part, by silencing. Using transient-transfection assays,
      we have localized a silencer element to a region between -128 and -480 bp
      upstream of the transcription initiation site. The silencing activity was
      overcome in a thyrotroph-specific manner by an unknown enhancer located in the
      sequences at -approximately 10000 to -1200 bp. The ubiquitous POU homeodomain
      protein Oct-1 recognized the A/T-rich silencer element at multiple sites in gel
      mobility shift assays and in vitro footprinting analyses. The silencing activity
      of Oct-1 was localized in its C-terminal alanine-rich domain, suggesting that Oct
      1 plays a role in silencing of the hTSHbeta promoter. Further, a significant
      fraction of Oct-1 was shown to be associated with the nuclear matrix, and the
      hTSHbeta silencer region was tethered to a nuclear matrix of human cells in vivo,
      suggesting a possible role of the Oct-1-hTSHbeta silencer region interaction in
      chromatin organization.

PMID- 8754838
TI  - Functional interaction of cytosolic hsp70 and a DnaJ-related protein, Ydj1p, in
      protein translocation in vivo.
AB  - In order to analyze the in vivo role of the SSA class of cytosolic 70-kDa heat
      shock proteins (hsps) of Saccharomyces cerevisiae, we isolated a temperature
      sensitive mutant of SSA1. The effect of a shift of mutant cells (ssa1ts ssa2 ssa3
      ssa4) from the permissive temperature of 23 degrees C to the nonpermissive
      temperature of 37 degrees C on the processing of several precursor proteins
      translocated into the endoplasmic reticulum or mitochondria was assessed. Of
      three mitochondrial proteins tested, the processing of only one, the beta subunit
      of the F1F0 ATPase, was dramatically affected. Of six proteins destined for the
      endoplasmic reticulum, the translocation of only prepro-alpha-factor and
      proteinase A was inhibited. The processing of prepro-alpha-factor was inhibited
      within 2 min of the shift to 37 degrees C, suggesting a direct effect of the
      hsp70 defect on translocation. More than 50% of radiolabeled alpha-factor
      accumulated in the precursor form, with the remainder rapidly reaching the mature
      form. However, the translocation block was complete, as the precursor form could
      not be chased through the translocation pathway. Since DnaJ-related proteins are
      known to interact with hsp70s and strains containing conditional mutations in a
      dnaJ-related gene, YDJ1, are defective in translocation of prepro-alpha-factor,
      we looked for a genetic interaction between SSA genes and YDJ1 in vivo. We found
      that a deletion mutation of YDJ1 was synthetically lethal in a ssa1ts ssa2 ssa3
      ssa4 background. In addition, a strain containing a single functional SSA gene,
      SSA1, and a deletion of YDJ1 accumulated the precursor form of alpha-factor.
      However, no genetic interaction was observed between a YDJ1 mutation and
      mutations in the SSB genes, which encode a second class of cytosolic hsp70
      chaperones. These results are consistent with SSA proteins and Ydj1p acting
      together in the translocation process.

PMID- 8754840
TI  - ROM7/BEM4 encodes a novel protein that interacts with the Rho1p small GTP-binding
      protein in Saccharomyces cerevisiae.
AB  - The RHO1 gene encodes a homolog of the mammalian RhoA small GTP-binding protein
      in the yeast Saccharomyces cerevisiae. Rho1p is localized at the growth site and
      is required for bud formation. The RHO1(G22S, D125N) mutation is a temperature
      sensitive and dominant negative mutation of RHO1, and a multicopy suppressor of
      RHO1(G22S, D125N), ROM7, was isolated. Nucleotide sequencing of ROM7 revealed
      that it is identical to the BEM4 gene (GenBank accession number L27816), although
      its physiological function has not yet been reported. Disruption of BEM4 resulted
      in the cold- and temperature-sensitive growth phenotypes, and cells of the
      deltabem4 mutant showed abnormal morphology, suggesting that BEM4 is involved in
      the budding process. The temperature-sensitive growth phenotype was suppressed by
      overexpression of RHO1, ROM2, which encodes a Rho1p-specific GDP/GTP exchange
      factor, or PKC1, which encodes a target of Rho1p. Moreover, glucan synthase
      activity, which is activated by Rho1p, was significantly reduced in the deltabem4
      mutant. Two-hybrid and biochemical experiments revealed that Bem4p directly
      interacts with the nucleotide-free form of Rho1p and, to lesser extents, with the
      GDP- and GTP-bound forms of Rho1p, although Bem4p showed neither GDP/GTP exchange
      factor, GDP dissociation inhibitor, nor GTPase-activating protein activity toward
      Rho1p. These results indicate that Bem4p is a novel protein directly interacting
      with Rho1p and is involved in the RHO1-mediated signaling pathway.

PMID- 8754839
TI  - Identification of the bud emergence gene BEM4 and its interactions with rho-type
      GTPases in Saccharomyces cerevisiae.
AB  - The Rho-type GTPase Cdc42p is required for cell polarization and bud emergence in
      Saccharomyces cerevisiae. To identify genes whose functions are linked to CDC42,
      we screened for (i) multicopy suppressors of a Ts- cdc42 mutant, (ii) mutants
      that require multiple copies of CDC42 for survival, and (iii) mutations that
      display synthetic lethality with a partial-loss-of-function allele of CDC24,
      which encodes a guanine nucleotide exchange factor for Cdc42p. In all three
      screens, we identified a new gene, BEM4. Cells from which BEM4 was deleted were
      inviable at 37 degrees C. These cells became unbudded, large, and round,
      consistent with a model in which Bem4p acts together with Cdc42p in polarity
      establishment and bud emergence. In some strains, the ability of CDC42 to serve
      as a multicopy suppressor of the Ts- growth defect of deltabem4 cells required co
      overexpression of Rho1p, which is an essential Rho-type GTPase necessary for cell
      wall integrity. This finding suggests that Bem4p also affects Rho1p function.
      Bem4p displayed two-hybrid interactions with Cdc42p, Rho1p, and two of the three
      other known yeast Rho-type GTPases, suggesting that Bem4p can interact with
      multiple Rho-type GTPases. Models for the role of Bem4p include that it serves as
      a chaperone or modulates the interaction of these GTPases with one or more of
      their targets or regulators.

PMID- 8754842
TI  - A double-strand break within a yeast artificial chromosome (YAC) containing human
      DNA can result in YAC loss, deletion or cell lethality.
AB  - Human chromosomal DNA contains many repeats which might provide opportunities for
      DNA repair. We have examined the consequences of a single double-strand break
      (DSB) within a 360-kb dispensable yeast artificial chromosome (YAC) containing
      human DNA (YAC12). An Alu-URA3-YZ sequence was targeted to several Alu sites
      within the YAC in strains of the yeast Saccharomyces cerevisiae; the strains
      contained a galactose-inducible HO endonuclease that cut the YAC at the YZ site.
      The presence of a DSB in most YACs led to deletion of the URA3 cassette, with
      retention of the telomeric markers, through recombination between surrounding
      Alus. For two YACs, the DSBs were not repaired and there was a G2 delay
      associated with the persistent DSBs. The presence of persistent DSBs resulted in
      cell death even though the YACs were dispensable. Among the survivors of the
      persistent DSBs, most had lost the YAC. By a pullback procedure, cell death was
      observed to begin at least 6 h after induction of a break. For YACs in which the
      DSB was rapidly repaired, the breaks did not cause cell cycle delay or lead to
      cell death. These results are consistent with our previous conclusion that a
      persistent DSB in a plasmid (YZ-CEN) also caused lethality (C. B. Bennett, A. L.
      Lewis, K. K. Baldwin, and M. A. Resnick, Proc. Natl. Acad. Sci. USA 90:5613-5617,
      1993). However, a break in the YZ-CEN plasmid did not induce lethality in the
      strain (CBY) background used in the present study. The differences in survival
      levels appear to be due to the rapid degradation of the plasmid in the CBY
      strain. We, therefore, propose that for a DSB to cause cell cycle delay and death
      by means other than the loss of essential genetic material, it must remain
      unrepaired and be long-lived.

PMID- 8754841
TI  - Conformational alteration of Oct-1 upon DNA binding dictates selectivity in
      differential interactions with related transcriptional coactivators.
AB  - VP16 (termed VP16-H here) of herpes simplex virus (HSV) belongs to a family of
      related regulatory proteins which includes VP16-B of bovine herpesvirus (BHV). We
      show that VP16-B, while also being a powerful transactivator of transcription
      dependent on Oct-1 binding sites in its target promoters, has virtually no
      activity on a defined VP16-H-responsive, octamer-containing target promoter.
      While Oct-1 binds equally well to the VP16-B-responsive and -nonresponsive sites,
      VP16-B interacts with Oct-1 only when Oct-1 is bound to the BHV octamer site and
      not when it is bound to the HSV site. We show from the analysis of chimeric
      proteins that the ability of VP16-B to discriminate between the Oct-1 forms
      depends on features of its N-terminal region. We also show from an analysis of
      chimeric DNA motifs that sequences that lie 3' to the POU domain-contacting
      region of the HSV octamer site play a role in making it unresponsive to VP16-B.
      Finally, we show by high-resolution hydroxyl radical footprint analysis that the
      conformation of Oct-l is different on the two sites. These results augment our
      previous report on an allosteric effect of DNA signals on the conformation of
      bound proteins and indicate that different conformations of the same DNA binding
      protein can be recognized selectively by related members of interacting
      regulatory proteins. The possible implications of our observations for selective
      gene regulation by Oct-1, a ubiquitous transcription factor, and other
      multimember transcription families are discussed.

PMID- 8754843
TI  - Effects of nonsense mutations on nuclear and cytoplasmic adenine
      phosphoribosyltransferase RNA.
AB  - We have analyzed Chinese hamster ovary (CHO) cell mutants bearing nonsense codons
      in four of the five exons of the adenine phosphoribosyltransferase (aprt) gene
      and have found a pattern of mRNA reduction similar to that seen in systems
      studied previously: a decrease in steady-state mRNA levels of 5- to 10-fold for
      mutations in exons 1, 2, and 4 but little effect for mutations in the 3'-most
      exon (exon 5). Nuclear aprt mRNA levels showed a similar decrease. Nonsense
      containing aprt mRNA decayed at the same rate as wild-type mRNA in these cell
      lines after inhibition of transcription with actinomycin D. Nonsense-containing
      aprt mRNA is associated with polysomes, ruling out a model in which stable
      residual mRNA escapes degradation by avoiding translation initiation. A
      tetracycline-responsive form of the aprt gene was used to compare the stability
      of nonsense-containing and wild-type aprt mRNAs without globally inhibiting
      transcription. In contrast to measurements made in the presence of actinomycin D,
      after inhibition of aprt transcription with tetracycline, a nonsense-mediated
      destabilization of aprt mRNA was indeed demonstrable. The increased rate of decay
      of cytoplasmic aprt mRNA seen here could account for the nonsense-mediated
      reduction in steady-state levels of aprt mRNA. However, the low levels of
      nonsense-bearing aprt mRNA in the nucleus suggest a sensibility of mRNA to
      translation or translatability before it exits that compartment. Quantitation of
      the steady-state levels of transcripts containing introns revealed no
      accumulation of partially spliced aprt RNA and hence no indication of nonsense
      mediated aberrancies in splicing. Our results are consistent with a model in
      which translation facilitates the export of mRNA through a nuclear pore. However,
      the mechanism of this intriguing nucleocytoplasmic communication remains to be
      determined.

PMID- 8754844
TI  - The sensitivity of Cockayne's syndrome cells to DNA-damaging agents is not due to
      defective transcription-coupled repair of active genes.
AB  - Two of the hallmarks of Cockayne's syndrome (CS) are the hypersensitivity of
      cells to UV light and the lack of recovery of the ability to synthesize RNA
      following exposure of cells to UV light, in spite of the normal repair capacity
      at the overall genome level. The prolonged repressed RNA synthesis has been
      attributed to a defect in transcription-coupled repair, resulting in slow removal
      of DNA lesions from the transcribed strand of active genes. This model predicts
      that the sensitivity of CS cells to another DNA-damaging agent, i.e., the UV
      mimetic agent N-acetoxy-2-acetylaminofluorene (NA-AAF), should also be associated
      with a lack of resumption of RNA synthesis and defective transcription-coupled
      repair of NA-AAF-induced DNA adducts. We tested this by measuring the rate of
      excision of DNA adducts in the adenosine deaminase gene of primary normal human
      fibroblasts and two CS (complementation group A and B) fibroblast strains. High
      performance liquid chromatography analysis of DNA adducts revealed that N
      (deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF) was the main adduct induced by NA
      AAF in both normal and CS cells. No differences were found between normal and CS
      cells with respect to induction of this lesion either at the level of the genome
      overall or at the gene level. Moreover, repair of dG-C8-AF in the active
      adenosine deaminase gene occurred at similar rates and without strand specificity
      in normal and CS cells, indicating that transcription-coupled repair does not
      contribute significantly to repair of dG-C8-AF in active genes. Yet CS cells are
      threefold more sensitive to NA-AAF than are normal cells and are unable to
      recover the ability to synthesize RNA. Our data rule out defective transcription
      coupled repair as the cause of the increased sensitivity of CS cells to DNA
      damaging agents and suggest that the cellular sensitivity and the prolonged
      repressed RNA synthesis are primarily due to a transcription defect. We
      hypothesize that upon treatment of cells with either UV or NA-AAF, the basal
      transcription factor TFIIH becomes involved in nucleotide excision repair and
      that the CS gene products are involved in the conversion of TFIIH back to the
      transcription function. In this view, the CS proteins act as repair-transcription
      uncoupling factors. If the uncoupling process is defective, RNA synthesis will
      stay repressed, causing cellular sensitivity. Since transcription is essential
      for transcription-coupled repair, the CS defect will affect those lesions whose
      repair is predominantly transcription coupled, i.e., UV-induced cyclobutane
      pyrimidine dimers.

PMID- 8754845
TI  - Inhibition of p53-mediated growth arrest by overexpression of cyclin-dependent
      kinases.
AB  - Rat fibroblasts transformed by a temperature-sensitive mutant of murine p53
      undergo a reversible growth arrest in G1 at 32.5 degrees C, the temperature at
      which p53 adopts a wild-type conformation. The arrested cells contain inactive
      cyclin-dependent kinase 2 (cdk2) despite the presence of high levels of cyclin E
      and cdk-activating kinase activity. This is due in part to p53-dependent
      expression of the p2l cdk inhibitor. Upon shift to 39 degrees C, wild-type p53 is
      lost and cdk2 activation and pRb phosphorylation occur concomitantly with loss of
      p2l. This p53-mediated growth arrest can be abrogated by overexpression of cdk4
      and cdk6 but not cdk2 or cyclins, leading to continuous proliferation of
      transfected cells in the presence of wild-type p53 and p2l. Kinase-inactive
      counterparts of cdk4 and cdk6 also rescue these cells from growth arrest,
      implicating a noncatalytic role for cdk4 and cdk6 in this resistance to p53
      mediated growth arrest. Aberrant expression of these cell cycle kinases may thus
      result in an oncogenic interference with inhibitors of cell cycle progression.

PMID- 8754846
TI  - A new class of activation-defective TATA-binding protein mutants: evidence for
      two steps of transcriptional activation in vivo.
AB  - Using a genetic screen, we isolated four TATA-binding protein (TBP) mutants that
      are specifically defective in vivo for the response to acidic activators. In
      contrast to previously described activation-defective TBP mutants, these TBP
      derivatives are not specifically defective for interactions with TATA elements or
      TFIIA. Three of these derivatives interact normally with a TATA element, TFIIA,
      TFIIB, or an acidic activation domain; presumably, they affect another protein
      protein interaction important for transcriptional activation. The remaining
      derivative (with F-237 replaced by D) binds a TATA element with wild-type
      affinity, but the TBP-TATA complex has an altered electrophoretic mobility and
      interacts poorly with TFIIA and TFIIB; this suggests that the conformation of the
      TBP-TATA element complex plays a role in transcriptional activation. To determine
      the step at which the TBP derivatives were unable to activate transcription, we
      utilized an artificial recruitment assay in which TBP is targeted to the promoter
      via fusion to the LexA DNA-binding domain. Consistent with previous evidence that
      acidic activators can increase recruitment of TBP to the promoter in vivo, the
      activation defect of some of these TBP derivatives can be corrected by artificial
      recruitment. In contrast, the activation defect of the other TBP derivatives is
      not bypassed by artificial recruitment. Thus, these TBP mutants define two steps
      in the process of transcriptional stimulation by acidic activators: efficient
      recruitment to the TATA element and a postrecruitment interaction with a
      component(s) of the initiation complex.

PMID- 8754847
TI  - In vivo genomic footprinting of thyroid hormone-responsive genes in pituitary
      tumor cell lines.
AB  - We studied the effects of thyroid hormone (T3) on nuclear protein-DNA
      interactions by using dimethyl sulfate (DMS) and DNase I ligation-mediated PCR
      footprinting. We examined an endogenous gene the growth hormone (GH) gene, and a
      stably transfected plasmid containing the chicken lysozyme silencer (F2) T3
      response element (TRE) gene, F2-TRE-TK-CAT, both in pituitary tumor (GC) cells.
      The 235-1 cell line, which expresses prolactin (PRL) and Pit-1, but not the T3
      receptor (TR) or GH, was used as a control. DMS and DNase I footprinting
      identified protected G residues in the Pit-1, Sp1, and Zn-15 binding sites of the
      GH gene in GC, but not in 235-1, cells. There was no specific protection of the
      tripartite GH TRE at -180 bp against either DMS or DNase I in the absence or
      presence of T3 in either cell line. However, T3 increased protection of the Pit-1
      and Sp1 binding sites against DMS in GC cells. In GC cells stably transfected
      with a plasmid containing F2-TRE-TK-CAT or TRalpha, chloramphenicol
      acetyltransferase expression was T3 inducible and DMS footprinting revealed both
      F2 TRE TR-binding half sites in a pattern suggesting the binding of TR homodimers
      before and during T3 exposure. We conclude that the GH gene is accessible to
      specific nuclear proteins in GC, but not in 235-1, cells and that T3 enhances
      this interaction, although there is no evidence of TR binding to the low-affinity
      rat GH TRE. The presence of TR binding to the high-affinity F2 TRE before and
      during T3 exposure suggests that reversible interaction of T3 with DNA-bound TRs,
      rather than transient T3-TR contact with TREs, determines the level of T3
      stimulated transcriptional activation.

PMID- 8754848
TI  - Loss of sustained Fus3p kinase activity and the G1 arrest response in cells
      expressing an inappropriate pheromone receptor.
AB  - The yeast pheromone response pathway is mediated by two G protein-linked
      receptors, each of which is expressed only in its specific cell type. The STE3DAF
      mutation results in inappropriate expression of the a-factor receptor in MATa
      cells. Expression of this receptor in the inappropriate cell type confers
      resistance to pheromone-induced G1 arrest, a phenomenon that we have termed
      receptor inhibition. The ability of STE3DAF cells to cycle in the presence of
      pheromone was found to correlate with reduced phosphorylation of the cyclin
      dependent kinase inhibitor Far1p. Measurement of Fus3p mitogen-activated protein
      (MAP) kinase activity in wild-type and STE3DAF cells showed that induction of
      Fus3p activity was the same in both strains at times of up to 1 h after pheromone
      treatment. However, after 2 or more hours, Fus3p activity declined in STE3DAF
      cells but remained high in wild-type cells. The level of inducible FUS1 RNA
      paralleled the changes seen in Fus3p activity. Short-term activation of the Fus3p
      MAP kinase is therefore sufficient for the early transcriptional induction
      response to pheromone, but sustained activation is required for cell cycle
      arrest. Escape from the cell cycle arrest response was not seen in wild-type
      cells treated with low doses of pheromone, indicating that receptor inhibition is
      not simply a result of weak signaling but rather acts selectively at late times
      during the response. STE3DAF was found to inhibit the pheromone response pathway
      at a step between the G beta subunit and Ste5p, the scaffolding protein that
      binds the components of the MAP kinase phosphorylation cascade. Overexpression of
      Ste20p, a kinase thought to act between the G protein and the MAP kinase cascade,
      suppressed the STE3DAF phenotype. These findings are consistent with a model in
      which receptor inhibition acts by blocking the signaling pathway downstream of G
      protein dissociation and upstream of MAP kinase cascade activation, at a step
      that could directly involve Ste20p.

PMID- 8754849
TI  - A consensus motif in the RFX DNA binding domain and binding domain mutants with
      altered specificity.
AB  - The RFX DNA binding domain is a novel motif that has been conserved in a growing
      number of dimeric DNA-binding proteins, having diverse regulatory functions, in
      eukaryotic organisms ranging from yeasts to humans. To characterize this novel
      motif, we have performed a detailed dissection of the site-specific DNA binding
      activity of RFX1, a prototypical member of the RFX family. First, we have
      performed a site selection procedure to define the consensus binding site of
      RFX1. Second, we have developed a new mutagenesis-selection procedure to derive a
      precise consensus motif, and to test the accuracy of a secondary structure
      prediction, for the RFX domain. Third, a modification of this procedure has
      allowed us to isolate altered-specificity RFX1 mutants. These results should
      facilitate the identification both of additional candidate genes controlled by
      RFX1 and of new members of the RFX family. Moreover, the altered-specificity RFX1
      mutants represent valuable tools that will permit the function of RFX1 to be
      analyzed in vivo without interference from the ubiquitously expressed endogenous
      protein. Finally, the simplicity, efficiency, and versatility of the selection
      procedure we have developed make it of general value for the determination of
      consensus motifs, and for the isolation of mutants exhibiting altered functional
      properties, for large protein domains involved in protein-DNA as well as protein
      protein interactions.

PMID- 8754850
TI  - Germ line-specific expression of intracisternal A-particle retrotransposons in
      transgenic mice.
AB  - Intracisternal A-particle (IAP) sequences are endogenous retrovirus-like mobile
      elements, or retrotransposons, present at 1,000 copies in the mouse genome. These
      elements transpose in a replicative manner via an RNA intermediate and its
      reverse transcription, and their transposition should therefore be tightly
      controlled by their transcription level. To analyze the in vivo pattern of
      expression of these retrovirus-like elements, we constructed several independent
      transgenic mice with either a complete IAP element marked with an intron or with
      the IAP promoter, or long terminal repeat (LTR), alone controlling the expression
      of a lacZ reporter gene with a nuclear localization signal. For all transgenic
      lines analyzed, IAP expression as determined by reverse transcription-PCR
      analysis was found to be essentially restricted to the male germ line.
      Furthermore, in situ 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal)
      staining of all organs disclosed specific beta-galactosidase-positive blue cells
      only within the testis, found as patches along the seminiferous tubules and often
      organized as assemblies of 2, 4, 8, or 16 cells. Histochemical analyses of
      tissues from 13.5-day-old embryos to adults demonstrated that this LTR activity
      is restricted to gonocytes and premeiotic undifferentiated spermatogonia.
      Finally, analysis of the methylation status of both transgenes and endogenous IAP
      LTRs demonstrated identical patterns, with methylation in somatic tissues and
      hypomethylation in the testis. Transgenic mice therefore reveal an intrinsic,
      highly restricted IAP expression which had escaped detection in previous global
      Northern (RNA) blot analyses and with possible strong biological relevance, as
      IAP activation specifically within the germ line might be a way to generate
      diversity at the evolutionary level without being deleterious to individuals.

PMID- 8754851
TI  - Cellular transformation and malignancy induced by ras require c-jun.
AB  - ras is an important oncogene in experimental animals and humans. In addition,
      activated ras proteins are potent inducers of the transcription factor AP-1,
      which is composed of heterodimeric complexes of Fos and Jun proteins. Together
      with the fact that deregulated expression of some AP-1 proteins can cause
      neoplastic transformation, this finding suggests that AP-1 may function as a
      critical ras effector. We have tested this hypothesis directly by analyzing the
      response to activated ras in cells that harbor a null mutation in the c-jun gene.
      The transcriptional response of AP-1-responsive genes to activated ras is
      severely impaired in c-jun null fibroblasts. Compared with wild-type cells, the c
      jun null cells lack many characteristics of ras transformation, including loss of
      contact inhibition, anchorage independence, and tumorigenicity in nude mice;
      these properties are restored by forced expression of c-jun. Rare tumorigenic
      variants of ras-expressing c-jun null fibroblasts do arise. Analysis of these
      variants reveals a consistent restoration of AP-1 activity. The results provide
      genetic evidence that c-jun is a crucial effector for transformation by activated
      ras proteins.

PMID- 8754852
TI  - An 18-base-pair sequence in the mouse proalpha1(II) collagen gene is sufficient
      for expression in cartilage and binds nuclear proteins that are selectively
      expressed in chondrocytes.
AB  - The molecular mechanisms by which mesenchymal cells differentiate into
      chondrocytes are still poorly understood. We have used the gene for a chondrocyte
      marker, the proalpha1(II) collagen gene (Col2a1), as a model to delineate a
      minimal sequence needed for chondrocyte expression and identify chondrocyte
      specific proteins binding to this sequence. We previously localized a cartilage
      specific enhancer to 156 bp of the mouse Col2a1 intron 1. We show here that four
      copies of a 48-bp subsegment strongly increased promoter activity in transiently
      transfected rat chondrosarcoma (RCS) cells and mouse primary chondrocytes but not
      in 10T1/2 fibroblasts. They also directed cartilage specificity in transgenic
      mouse embryos. These 48 bp include two 11-bp inverted repeats with only one
      mismatch. Tandem copies of an 18-bp element containing the 3' repeat strongly
      enhanced promoter activity in RCS cells and chondrocytes but not in fibroblasts.
      Transgenic mice harboring 12 copies of this 18-mer expressed luciferase in ribs
      and vertebrae and in isolated chondrocytes but not in noncartilaginous tissues
      except skin and brain. In gel retardation assays, an RCS cell-specific protein
      and another closely related protein expressed only in RCS cells and primary
      chondrocytes bound to a 10-bp sequence within the 18-mer. Mutations in these 10
      bp abolished activity of the multimerized 18-bp enhancer, and deletion of these
      10 bp abolished enhancer activity of 465- and 231-bp intron 1 segments. This
      sequence contains a low-affinity binding site for POU domain proteins, and
      competition experiments with a high-affinity POU domain binding site strongly
      suggested that the chondrocyte proteins belong to this family. Together, our
      results indicate that an 18-bp sequence in Col2a1 intron 1 controls chondrocyte
      expression and suggest that RCS cells and chondrocytes contain specific POU
      domain proteins involved in enhancer activity.

PMID- 8754853
TI  - Distinct gene expression patterns in skeletal and cardiac muscle are dependent on
      common regulatory sequences in the MLC1/3 locus.
AB  - The myosin light-chain 1/3 locus (MLC1/3) is regulated by two promoters and a
      downstream enhancer element which produce two protein isoforms in fast skeletal
      muscle at distinct stages of mouse embryogenesis. We have analyzed the expression
      of transcripts from the internal MLC3 promoter and determined that it is also
      expressed in the atria of the heart. Expression from the MLC3 promoter in these
      striated muscle lineages is differentially regulated during development. In
      transgenic mice, the MLC3 promoter is responsible for cardiac-specific reporter
      gene expression while the downstream enhancer augments expression in skeletal
      muscle. Examination of the methylation status of endogenous and transgenic
      promoter and enhancer elements indicates that the internal promoter is not
      regulated in a manner similar to that of the MLC1 promoter or the downstream
      enhancer. A GATA protein consensus sequence in the proximal MLC3 promoter but not
      the MLC1 promoter binds with high affinity to GATA-4, a cardiac muscle- and gut
      specific transcription factor. Mutation of either the MEF2 or GATA motifs in the
      MLC3 promoter attenuates its activity in both heart and skeletal muscles,
      demonstrating that MLC3 expression in these two diverse muscle types is dependent
      on common regulatory elements.

PMID- 8754854
TI  - Translation of a testis-specific Cu/Zn superoxide dismutase (SOD-1) mRNA is
      regulated by a 65-kilodalton protein which binds to its 5' untranslated region.
AB  - Mouse testes contain two distinct superoxide dismutase (SOD-1) transcripts which
      differ by 114 nucleotides in their 5' untranslated regions (UTRs) (W. Gu, C.
      Morales, and N. B. Hecht, J. Biol. Chem. 270:236-243, 1995). The shorter SOD-1
      mRNA, a somatic type SOD-I mRNA (SSOD-1), is ubiquitously expressed in all
      somatic tissues as well as in testes. The larger SOD-1 mRNA, a testis-specific
      SOD-1 mRNA (TSOD-1), derived from an alternative upstream start site, is
      transcribed solely in postmeiotic germ cells and is translationally regulated
      during spermiogenesis. Since the two mRNAs have identical nucleotides except that
      TSOD-1 has an additional sequence at its 5' terminus, we have proposed that the
      extra 5' UTR sequence may be involved in the translational control of the TSOD-1
      mRNA during spermiogenesis. Here we show that, when assayed in a cell-free
      system, TSOD-1 is translated only slightly less efficiently than SSOD-1. RNA gel
      retardation and UV cross-linking assays reveal that a testicular cytoplasmic
      protein (Cu/Zn superoxide dismutase RNA-binding protein [SOD-RBP]) of about 65
      kDa specifically binds to the extended 5' UTR of TSOD-1. After purification of
      SOD-RBP by RNA affinity chromatography, we demonstrate that SOD-RBP can repress
      the in vitro translation of TSOD-1 mRNA but not SSOD-1 mRNA or cotranslated
      luciferase mRNA. We conclude that SOD-RBP serves as a repressor in the
      translation of TSOD-1 mRNA during spermiogenesis and thereby fine-tunes the level
      of Cu/Zn superoxide dismutase produced in maturing germ cells.

PMID- 8754855
TI  - Precise alignment of sites required for mu enhancer activation in B cells.
AB  - The lymphocyte-specific immunoglobulin mu heavy-chain gene intronic enhancer is
      regulated by multiple nuclear factors. The previously defined minimal enhancer
      containing the muA, muE3, and muB sites is transactivated by a combination of the
      ETS-domain proteins PU.1 and Ets-1 in nonlymphoid cells. The core GGAAs of the
      muA and muB sites are separated by 30 nucleotides, suggesting that ETS proteins
      bind to these sites from these same side of the DNA helix. We tested the
      necessity for appropriate spatial alignment of these elements by using mutated
      enhancers with altered spacings. A 4- or 10-bp insertion between muE3 and muB
      inactivated the mu enhancer in S194 plasma cells but did not affect in vitro
      binding of Ets-1, PU.1, or the muE3-binding protein TFE3, alone or in pairwise
      combinations. Circular permutation and phasing analyses demonstrated that PU.1
      binding but not TFE3 or Ets-1 bends mu enhancer DNA toward the major groove. We
      propose that the requirement for precise spacing of the muA and muB elements is
      due in part to a directed DNA bend induced by PU.1.

PMID- 8754856
TI  - De novo methylation of CpG island sequences in human fibroblasts overexpressing
      DNA (cytosine-5-)-methyltransferase.
AB  - Recent studies showing a correlation between the levels of DNA (cytosine-5-)
      methyltransferase (DNA MTase) enzyme activity and tumorigenicity have implicated
      this enzyme in the carcinogenic process. Moreover, hypermethylation of CpG island
      containing promoters is associated with the inactivation of genes important to
      tumor initiation and progression. One proposed role for DNA MTase in
      tumorigenesis is therefore a direct role in the de novo methylation of these
      otherwise unmethylated CpG islands. In this study, we sought to determine whether
      increased levels of DNA MTase could directly affect CpG island methylation. A
      full-length cDNA for human DNA MTase driven by the cytomegalovirus promoter was
      constitutively expressed in human fibroblasts. Individual clones derived from
      cells transfected with DNA MTase (HMT) expressed 1- to 50-fold the level of DNA
      MTase protein and enzyme activity of the parental cell line or clones transfected
      with the control vector alone (Neo). To determine the effects of DNA MTase
      overexpression on CpG island methylation, we examined 12 endogenous CpG island
      loci in the HMT clones. HMT clones expressing > or = 9-fold the parental levels
      of DNA MTase activity were significantly hypermethylated relative to at least 11
      Neo clones at five CpG island loci. In the HMT clones, methylation reached nearly
      100% at susceptible CpG island loci with time in culture. In contrast, there was
      little change in the methylation status in the Neo clones over the same time
      frame. Taken together, the data indicate that overexpression of DNA MTase can
      drive the de novo methylation of susceptible CpG island loci, thus providing
      support for the idea that DNA MTase can contribute to tumor progression through
      CpG island methylation-mediated gene inactivation.

PMID- 8754857
TI  - Unimpaired macrophage differentiation and activation in mice lacking the zinc
      finger transplantation factor NGFI-A (EGR1).
AB  - The zinc finger protein NGFI-A (also called EGR1, Krox24, or zif268) is a
      candidate regulator of myeloid cell differentiation. Evidence supporting this
      hypothesis is twofold. First, NGFI-A antisense oligonucleotides prevent
      macrophage differentiation in HL-60 and U937 myeloid leukemia cell lines and in
      normal bone marrow cells. Second, enforced expression of NGFI-A blocks
      granulocytic differentiation and promotes macrophage differentiation in HL-60
      cells and in the hematopoietic progenitor cell line 32D. We sought to determine
      the effect of NGFI-A deficiency on macrophage differentiation and function in
      vivo by examining native bone marrow cells from mice homozygous for a disrupted
      allele of NGFI-A derived from gene-targeted ES cells. Macrophages were observed
      in peripheral blood and several tissues, indicating that NGFI-A was not required
      for the formation of a variety of macrophage compartments. No differences in
      myeloid cell differentiation were observed between wild-type and NGFI-A-/- bone
      marrow cells cultured in the presence of macrophage, granulocyte-macrophage, or
      granulocyte colony-stimulating factor (M-CSF, GM-CSF, or G-CSF). Activation of
      NGFI-A-/- macrophages was comparable to that of wild-type macrophages as
      determined by nitric oxide production and increased cell surface expression of
      class II major histocompatibility complex molecules. Moreover, NGFI-A-/- mice
      showed no increased mortality or bacteria] burden when challenged with Listeria
      monocytogenes. Together, these results indicate that NGFI-A is not required for
      macrophage differentiation or activation.

PMID- 8754858
TI  - Dephosphorylation of threonine 169 of Cdc28 is not required for exit from mitosis
      but may be necessary for start in Saccharomyces cerevisiae.
AB  - Entry into mitosis requires activation of cdc2 kinase brought on by its
      association with cyclin B, phosphorylation of the conserved threonine (Thr-167 in
      Schizosaccharomyces pombe) in the T loop, and dephosphorylation of the tyrosine
      residue at position 15. Exit from mitosis, on the other hand, is induced by
      inactivation of cdc2 activity via cyclin destruction. It has been suggested that
      in addition to cyclin degradation, dephosphorylation of Thr-167 may also be
      required for exit from the M phase. Here we show that Saccharomyces cerevisiae
      cells expressing cdc28-E169 (a CDC28 allele in which the equivalent threonine,
      Thr-169, has been replaced by glutamic acid) are able to degrade mitotic cyclin
      Clb2, inactivate the Cdc28/Clb2 kinase, and disassemble the anaphase spindles,
      suggesting that they exit mitosis normally. The cdc28-E169 allele is active with
      respect to its mitotic functions, since it complements the mitosis-defective
      cdc28-1N allele. Whereas replacement of Thr-169 with serine affects neither Start
      nor the mitotic activity of Cdc28, replacement with glutamic acid or alanine
      renders Cdc28 inactive for Start-related functions. Coimmunoprecipitation
      experiments show that although Cdc28-E169 associates with mitotic cyclin Clb2, it
      fails to associate with the G1 cyclin Cln2. Thus, an unmodified threonine at
      position 169 in Cdc28 is important for interaction with G1 cyclins. We propose
      that in S. cerevisiae, dephosphorylation of Thr-169 is not required for exit from
      mitosis but may be necessary for commitment to the subsequent division cycle.

PMID- 8754859
TI  - Uridine insertion into preedited mRNA by a mitochondrial extract from Leishmania
      tarentolae: stereochemical evidence for the enzyme cascade model.
AB  - An RNA editing-like internal uridine (U) incorporation activity (G. C. Frech, N.
      Bakalara, L Simpson, and A. M. Simpson, EMBO J. 14:178-187, 1995) and a 3'
      terminal U addition activity (N. Bakalara, A. M. Simpson, and L. Simpson, J.
      Biol. Chem. 264:18679-18686, 1989) have been previously described by using a
      mitochondrial extract from Leishmania tarentolae. Chiral phosphorothioates were
      used to investigate the stereoconfiguration requirements and the stereochemical
      course of these nucleotidyl transfer reactions. The extract utilizes (SP)-alpha-S
      UTP for both 3' and internal U incorporation into substrate RNA. The internal as
      well as the 3' incorporation of (SP)-alpha-S-UTP proceeds via inversion of the
      stereoconfiguration. Furthermore, internal U incorporation does not occur at
      sites containing thiophosphodiesters of the RP configuration. Our results are
      compatible with an enzyme cascade model for this in vitro U insertion activity
      involving sequential endonuclease and uridylyl transferase directly from UTP and
      RNA ligase steps and are incompatible with models involving the transfer of U
      residues from the 3' ends of guide RNAs.

PMID- 8754860
TI  - Development and characterization of v-myc/v-raf-transformed murine fetal
      thymocyte cell lines.
AB  - Transformed murine fetal thymocyte cell lines were derived by incubating fetal
      thymic organ cultures with a v-myc/v-raf-containing retroviral construct in order
      to model developmental stages within the early triple negative (CD3-CD4-CD8-)
      thymocyte population. The resulting 10 cell lines had a lymphoid morphology, were
      all CD44+, CD90+, and were triple negative by surface antigen analysis. The cell
      lines, however, were distinguishable by differences in the expression of T cell
      associated and T cell-specific genes. The CD3 genes were observed to be
      discoordinately expressed, in that CD3 gamma chain gene expression was detected
      in 2 cell lines in the absence of CD3 delta and epsilon expression. Expression of
      the CD3 gamma chain gene was observed in cell lines without the expression of
      other T cell-specific genes or T cell receptor rearrangement and may be one of
      the earliest T cell-specific genes to be expressed. The transcription factor
      Ikaros was expressed in all 10 cell lines, whereas the transcription factor TCF1
      alpha was expressed only in the 2 most differentiated lines. In 8 cell lines,
      expression of partial TCR beta and/or TCR alpha transcripts was observed by
      Northern blot. In several lines, expression of rearranged TCR alpha transcripts
      in the absence of TCR beta transcripts was demonstrated; however, TCR beta DJ
      rearrangements were observed by Southern blot in all but 1 of these cell lines.
      Thus, these cell lines, ordered based on the general pattern of additive gene
      expression observed, may reflect various stages of triple-negative thymocyte
      differentiation and provide an in vitro mechanism to elucidate some of the
      molecular events involved in early thymocyte development.

PMID- 8754861
TI  - Extracellular activities of human granzymes. I. Granzyme A induces IL6 and IL8
      production in fibroblast and epithelial cell lines.
AB  - Situated in secretory granules of cytotoxic cells, granzymes are essential for
      induction of target cell apoptosis with perforin. However, since cytotoxic cells
      constitutively secrete a portion of their synthesized granzymes, these proteases
      could mediate extracellular functions independently of their role in the lytic
      event. Thrombin has been shown to function as an activation molecule by cleaving
      its receptor. We hypothesize that granzymes may act similarly. In this report, we
      show that purified human granzyme A can induce human lung fibroblasts to produce
      IL6 and IL8. Cytokine induction is abrogated by treating the serine protease with
      the suicide serine protease inhibitor 3,4-dichloroisocoumarin. Other fibroblast
      lines as well as epithelial cells produced cytokines in response to granzyme A.
      Our data suggest that granzyme A can function as an activation molecule with
      potentially important immunoregulatory functions.

PMID- 8754862
TI  - [Drug therapy of tuberculosis: history and present-day status].
AB  - Historical aspects of early and present-day chemotherapy of tuberculosis have
      been summarized for 5 decades. Chemotherapeutic approaches are specified in
      relation to different tuberculosis forms, duration, extension, bacterial
      discharge. 4 categories of patients at different treatment stages are recognized.
      The terms of after treatment cessation of bacterial discharge and cavern closure
      are detailed.

PMID- 8754863
TI  - [Drug resistance of Mycobacterium tuberculosis and its significance in the
      hospital practice].
AB  - The author describes the trends in frequency and nature of primary drug
      resistance throughout the last 3 decades. Favourable trends in 1980s changed for
      negative tendencies in 1990s which reflects deterioration of epidemiological
      situation by tuberculosis. Earlier establishment of drug resistance is possible
      basing on its direct determination in the conditions of massive bacterial
      discharge. In new-onset contacts antibioticogram should be primarily copied from
      that of contamination source, in recurrent disease antibioticogram should
      correspond to that obtained in the same patient at first test.

PMID- 8754864
TI  - [Characterization of tuberculosis agent in different regions of Russia and its
      significance in assessment of the epidemiological situation].
AB  - The authors analyze M. tuberculosis viability in terms of growth speed and
      intensity, drug sensitivity; compare bacteriological data with epidemiological
      (morbidity, primary bacillarity in respiratory tuberculosis, bacillary focus in
      populations, population with fibrocavernous tuberculosis); range epidemiological
      and bacteriological indices; determine integral indices of epidemiological and
      bacteriological situation; calculate Spirman's rate. It is thought possible to
      use the above bacteriological indices in analysis of epidemiological situation
      concerning tuberculosis.

PMID- 8754865
TI  - [Tuberculosis risk groups among children and principles of approach to
      chemoprophylaxis].
AB  - The trends in tuberculin reactions of Mantoux test (2 TU) performed annually
      before and after the diagnosis of tuberculosis shows that the risk groups consist
      of subjects with increasing tuberculin sensitivity and those susceptible to acute
      respiratory virus infections. An individual approach to prescription of
      chemoprophylaxis considering the number of risk factors (epidemiological, age
      sex, biomedical, social) is advisable. Sanatorium chemoprophylaxis is needed in
      the presence of at least 2 factors. A 3-month isoniazid chemoprophylaxis prevents
      the disease and normalizes sensitivity to tuberculin.

PMID- 8754866
TI  - [Tuberculosis in refugees from foreign countries].
AB  - Screening for tuberculosis has revealed active disease in 30 of 168 examinees.
      They have arrived in Russia as refugees from Somalia, Afghanistan, Angola and
      other countries. 24 refugees had pulmonary tuberculosis. Destruction of pulmonary
      tissues and massive discharge of M. tuberculosis were found in 10, 2 and 1
      patients with infiltrative, disseminated and fibrous-cavernous tuberculosis. A
      specific therapy with 3-4 drugs stopped discharge of the bacteria with sputum. It
      is stated that refugees from foreign countries may constitute a great
      epidemiological threat of tuberculosis for contacting Russian population.

PMID- 8754867
TI  - [Analysis of mortality of patients with pulmonary tuberculosis in the course of a
      year after its detection].
AB  - Autopsy protocols for 1989-1994 have been analyzed for 123 patients with
      pulmonary tuberculosis. Within the first year after the disease registration one
      sixth of the patients died. Most of them were males over 50 living in rural
      regions. Dominating were different forms of destructive pulmonary tuberculosis
      running concurrently with circulatory, respiratory, gastrointestinal diseases,
      alcoholism, diabetes mellitus.

PMID- 8754868
TI  - [Medico-social characteristics of inpatients with pulmonary tuberculosis].
AB  - A questionnaire survey of 103 patients with active tuberculosis of the
      respiratory organs provided evidence on social factors contributing to more
      frequent onset of destructive tuberculosis, complications, discharge of M.
      tuberculosis, associated chronic bronchitis and ulcer. These were: serving
      sentence in prison or reformatory, poverty, alcoholism. X-ray diagnosis of
      tuberculosis provided earlier detection of the disease reducing the number of
      complications and invalidity.

PMID- 8754869
TI  - [The centennial of the great discovery].

PMID- 8754870
TI  - [Radionuclide studies in phthisiology and pulmonology].

PMID- 8754871
TI  - [X-ray examinations in the differential diagnosis of spherical neoformations in
      the lungs].

PMID- 8754872
TI  - [Current status and problems of X-ray diagnosis].

PMID- 8754873
TI  - [Role of echography in pulmonary cancer].

PMID- 8754874
TI  - [Radionuclide study of capillary circulation in the lungs in rheumatism and
      sarcoidosis].

PMID- 8754875
TI  - [X-ray differential diagnosis of tuberculosis and pulmonary cancer complicated by
      lung diseases].

PMID- 8754876
TI  - [A comparative study of scintigraphic and morphologic changes in pulmonary
      vessels in tuberculosis].

PMID- 8754877
TI  - [Current role of fluorography in early detection of tuberculosis in adults].

PMID- 8754878
TI  - [Effectiveness of regional lymphotropic therapy in combined treatment of
      tuberculosis in adolescents].
AB  - Lymphotropic therapy was given to 32 adolescents with different forms of
      tuberculosis. In combined chemotherapy one of the antituberculous drugs
      (tubazide, kanamycin) was administered lymphotropically into pretracheal
      subcutaneous fat or into the axillary area on the affected side. Heparin served
      as a lymphostimulator. Lymphotropic therapy lasted from 1 to 3 months. The
      response came faster in patients on lymphotropic therapy.

PMID- 8754879
TI  - [Immunological indicators in patients with pulmonary tuberculosis in the presence
      of drug-resistant Mycobacteria].
AB  - Immunological indices for 121 pulmonary tuberculosis (PT) patients discharging
      drug-resistant M. tuberculosis were compared to those for 87 PT patients with M.
      tuberculosis sensitive to antibacterial drugs. The patients with drug-resistant
      bacteria before hospitalization had lower count of T-lymphocytes, altered
      proportion T-helpers/T-suppressors, reduced ability of T-lymphocytes for blast
      transformation in the presence of PHA and PPD. T-lymphocyte functional activity
      remained inhibited as compared to those patients discharging drug-sensitive
      mycobacteria.

PMID- 8754880
TI  - [Long-term results of surgical treatment of bilateral pulmonary tuberculosis in
      military personnel].
AB  - Long-term outcomes of surgical treatment have been analyzed for 204 servicemen
      admitted to hospital for bilateral tuberculosis in 1975-1990. A complete response
      was achieved in 191 (93.7%) patients. The recurrence occurred in 13 (6.3%)
      patients 5-7 years after their discharge from the hospital. All of them received
      a second course of antituberculous treatment. 98% of the patients resumed the
      service.

PMID- 8754881
TI  - [Morphology of active tuberculous coxitis in adults].
AB  - 16 patients with active tuberculous coxitis (ATC) aged 19-54 were treated
      surgically. Histological evidence on the removed tissue specimens from 6 patients
      elucidated a number of features characteristic for active specific inflammation
      in adults versus children. These are: balanced alternative-exudative and
      productive changes, absence of advanced necroses, purulent necrotic mass and
      formation of cavities and abscesses, presence of marked focal and diffuse
      leukocytic infiltration.

PMID- 8754882
TI  - [Study of immunobiological properties of specific immunomodulators of the
      adjuvant type in experimental tuberculosis].
AB  - CBA mice served as experimental tuberculosis model to study protective,
      immunomodulating and toxico-allergic properties of two drugs including cytoplasma
      and cell walls of BCG mycobacteria as well as of synthetic adjuvant
      polyoxidonium. Doses and schemes are presented developed for experimental
      tuberculosis treatment with cytoplasm and not causing toxico-allergic reactions
      in mice. The specific immunomodulator of cytoplasm, polyoxidonium, proved
      effective therapeutic modality in experimental mouse tuberculosis.

PMID- 8754883
TI  - [Morphology of the lungs and cellular composition of bronchoalveolar lavage in
      tuberculomas].
AB  - Morphology of the lungs and bronchoalveolar lavage (BAL) were studied in 27
      patients with tuberculomas. The investigators also determined lymphocytic,
      macrophagal or neutrophil BAL composition regarding lymphocyte, macrophage or
      neutrophil dominating infiltration of pulmonary tissue outside the sites of
      specific inflammation. As a result, the activity of the process was assessed by
      subpopulation composition of lymphocytes in BAL, by morphology of alveolar
      macrophages in pulmonary tissue; the pattern of inflammatory reaction in the
      lesion focus was specified.

PMID- 8754884
TI  - [Critical comments on the article by A.A. Priimak and A.L. Kucherov, "Conception
      of the organization of antituberculosis services in Russia" (Probl. Tub., 1955,
      No. 6, pp. 2-4)].

PMID- 8754885
TI  - [Use of millimetric microwaves in combined treatment of patients with pulmonary
      tuberculosis].

PMID- 8754886
TI  - [First Conference of Young Phthisio-Pulmonologists of Russia, "Tuberculosis and
      nonspecific lung diseases in studies of young researchers"].

PMID- 8754887
TI  - [Regional Scientific-Practical Conference, "Problems of tuberculosis in the
      Extreme North under new social and economic conditions"].

PMID- 8754888
TI  - [Method of pancreatoduodenal resection and intraoperative prevention of acute
      pancreatitis].
AB  - In the period from 1988 to 1991 the authors carried out 27 pancreatoduodenal
      resections with 11.1% mortality. From analysis of the results they formulated the
      main technical principles of this operation and suggested a complex of
      intraoperative measures for prevention of acute postoperative pancreatitis. The
      complex included application of a 5-fluorouracil-containing covering of the
      pancreas at the stage of exposure of the complex which will be removed;
      individualization of the methods for treatment of the pancreatic stump depending
      on the diameter of the pancreatic duct; the use of prolene in forming the
      pancreaticoenteroanastomosis; intraoperative administration of cephalosporins and
      dioxidine followed by antibacterial therapy; application of microsphere with
      cytostatics to the pancreas at the operation end for prolongation of pancreatic
      secretion suppression.

PMID- 8754889
TI  - [Enteral correction of homeostasis in acute pancreatitis].
AB  - The experiments showed that heart and liver functional abnormalities will take
      place even before changes of blood amylase is occurred. It was shown that
      Dalargin in a dose of 50 micrograms/kg will stimulate the intestinal absorption.

PMID- 8754890
TI  - [Surgical treatment of acute pancreatitis associated with biliary calculi].
AB  - Results of surgical treatment of acute pancreatitis combined with concrements of
      biliferous tract in 197 patients (108 females and 89 men) at the age of 25-78
      years are analysed. In all cases there was calculous cholecystitis, that was in
      126 (64%) cases combined with choledocholithiasis. In 141 (71,6%) patients there
      was edematic pancreatitis, in 56 (28,4%)-destructive pancreatitis. 29 patients
      had fatty pancreonecrosis, 12 patients-hemorrhagic pancreonecrosis, 15 patients
      mixed forms of pancreonecrosis. All the patients were operated on. Urgent surgery
      have been done in 62 (31,5%) patients, planned-in 135 (68,5%). The mortality rate
      after the urgent surgery was 16 (25,8%), after planned-5 (3,7%). The total
      postoperative mortality rate is 10,6%. The causes of mortality were: liver and
      kidney insufficiency (5), heart failure (5) infection (14).

PMID- 8754891
TI  - [Laparoscopic cholecystectomy: possibilities, shortcomings, prospects].
AB  - The results of surgical treatment of acute cholecystitis in 350 patients have
      been analysed. The role of concomitant diseases and age of a patients in choosing
      the method of surgical treatment is stressed. The advantages and shortcomings of
      the low-traumatic surgical methods are discussed. The way of choosing the proper
      surgical method in treatment of acute cholecystitis is proposed.

PMID- 8754892
TI  - [Clinical manifestations of cancer of the gallbladder].
AB  - The article deals with 14 cases of carcinoma of the gallbladder which were
      recognized during 750 operations performed for cholelithiasis in 1989-1991. The
      clinical manifestations were clearly subdivided into 2 groups of symptoms:
      carcinoma of the gallbladder with a clinical picture of acute cholecystitis, and
      carcinoma of the gallbladder with a clinical picture of cholestatic jaundice with
      clinical and biochemical indices of obstructive jaundice. Analysis of the
      clinical manifestations of carcinoma of the gallbladder, the difficult diagnosis
      of the disease, and the poor results of surgery led to the following conclusion:
      active recognition of cholelithiasis and timely surgical treatment of patient
      with the disease are necessary.

PMID- 8754893
TI  - [Diagnosis and surgical treatment of cavernous hemangioma of the liver].
AB  - Results of surgical treatment of cavernous liner hemangiomas in 47 patients have
      been analysed. In 7 cases the original method of surgery in unresectable liver
      hemangiomas was used. The method was designed by the authors of the article. The
      proper diagnosis of liver hemangiomas is possible in the specialized divisions
      only. Ultrasound examination, CT and laparoscopy play the major role in
      diagnosis. Anatomical liver resection is the major surgical method. In cases of
      unresectable hemangiomas the method of omento-hepatopexy with subsequent X-ray
      therapy is indicated.

PMID- 8754894
TI  - [One-stage esophagoplasty with pathologically changed or previously operated
      stomach].
AB  - The results of esophagus extirpation with subsequent one-stage esophagoplasty by
      pathologically changed or previously operated stomach in 50 patients are
      analysed. 2 patients had gastric and esophagus cancer and 48 patients esophagus
      strictures. 36 patients had been previously operated on their stomach, 10
      patients had scar deformation of the stomach after thermal burns, 2 patients had
      a giant leiomyoma. Isoperistaltic gastric tube was used as an esophagus
      substitute. The postoperative mortality rate was 2,1%. The optimal method of
      surgical treatment of the combined gastric and esophagus lesions is recommended.

PMID- 8754895
TI  - [Evaluation of the gastric outlet function of normal and operated stomach using
      ultrasound].
AB  - The functional condition of the gastric outlet was studied by ultrasound in 25
      individuals (the comparison group) and in 37 patients after organ-preserving
      operations for complicated pyloroduodenal ulcers. The diameter of the gastric
      outlet and the pylorus, the length of the pyloric canal were recorded during the
      examination and the presence or absence of duodenogastric reflux was noted. A
      duodenogastric reflux was found in 48% of persons of the comparison group, in 25%
      of patients after Judd's pyloroplasty and all patients after Finney's
      pyloroplasty. The data obtained provide evidence that the functional results are
      better in pylorus-preserving and pylorus-saving operations that in pylorus
      destroying operations which lead to loss of the obturation function of the
      pylorus.

PMID- 8754897
TI  - [Role of Helicobacter pylori in the etiology of duodenal ulcer recurrence after
      selective proximal vagotomy].
AB  - 126 patients with duodenal peptic ulcer were examined before and in different
      periods after operation for selective proximal vagotomy (SPV). Endoscopy was
      performed and Helicobacter pylori (HP) was detected by the urease,
      bacteriological, and histological methods. The urease test proved to be the most
      informative, simple, and available method for revealing infection of the gastric
      mucosa by HP. The frequency of HP detection by this method made up 97-98%. The
      frequency of ulcer recurrences after SPV coincided with the degree of
      contamination of the mucosa with HP and increased to 15% in high contamination.
      Treatment with agent eliminating HP in the early period after SPV promoted
      cicatrization of the ulcer.

PMID- 8754896
TI  - [First experience with vertical gastroplasty in the treatment of patients with
      4th-degree obesity].
AB  - The article discusses four operations for vertical gastroplasty performed for the
      first time in Russia at the Research Centre of Surgery, RAMS, for degree IV
      obesity (the body weight of the patients ranged from 115 to 183 kg). The suturing
      instruments CEEA-28, TA-90, and CIA-90 manufactured by Auto Suture Instruments,
      USA, were used. Subsequent examination of patients in follow-up periods of as
      long as 4 months showed a favorable effect of the operations: body weight
      reduced, the patient's health and the course of concomitant diseases was milder.

PMID- 8754898
TI  - [Lower anterior (mesenteric) resection of the rectum].
AB  - The immediate and late results of 283 operations for anterior resection of the
      rectum in carcinoma are analysed. Low anterior resection of the rectum with
      division of the lateral ligaments and middle rectal arteries was performed in 28
      (9.9 +/- 1.8%) of these patients. Due to the high incidence of anastomosis
      incompetence, the formation of colostomy in low anterior resections is
      obligatory. The discussed operation is justified oncologically and does not yield
      in radical character to rectal extirpation and abdomino-anal resection of the
      rectum with the pull-through procedure.

PMID- 8754899
TI  - [Prevention of incompetence of sigmoidorectal anastomosis after anterior
      resection of the rectum in cancer].
AB  - The results of surgery in 11 patients with rectal cancer are analysed. The
      anterior rectal resection was performed in all cases, in 38 cases-the lower
      resection was performed. The use of decompressive colostomy as a method to
      prevent complications, caused by anastomotic incompetence is recommended. The
      colostomy was used in 51.3% cases. Besides colostomy, in 27 (26.2%) patients the
      antiseptic connection elements impregnated with kanamycin, dioxidine and
      cephamezine were used to prevent sigmoido-rectal anastomotic incompetence. The
      rate of anastomotic incompetence was 12.6% (14 patients). There were no
      mortality. The use of decompressive colostomy in operations on transverse colon
      especially in cases of lower rectal resection and in patients with partial colon
      ileus is advocated. The use of antiseptic connective elements is an efficient
      method to prevent anastomotic incompetence.

PMID- 8754900
TI  - [Strategy of the surgeon in rectal injuries].
AB  - Mechanical rectal injuries are severe traumas of the gastrointestinal tract which
      often cause fatal complications. The etiology of injuries to the rectum is
      diverse. They are inflicted with knives, occur in blunt injury of the abdomen, in
      injury with foreign objects, in falling from a height on a sharp object.
      Particularly important are traumas occurring during medical manipulations: in
      giving an enema, during rectosigmoidoscopy and colonoscopy, in electrocoagulation
      of polyps. Various methods are applied for the treatment of rectal injuries in
      intra- and extraperitoneal traumas, and an individual approach is needed in each
      case.

PMID- 8754901
TI  - [Immediate and long-term results of the treatment in cancer of the large
      intestine].
AB  - Operative treatment of 200 patients with carcinoma of the rectum is analysed.
      Planned operations were conducted on 101 patients, postoperative mortality was
      7.8%. Surgery was undertaken in 93 patients with acute intestinal obstruction,
      postoperative mortality was 15.05%. Changes of the policy of treatment of
      patients with acute intestinal obstruction reduced postoperative mortality. Five
      year survival was 67.1%.

PMID- 8754902
TI  - [Variants of pathological motility of the large intestine in the abdominal cavity
      and methods of surgical correction].
AB  - The morphological analyses of variations of colon fixation in 200 cadavers and 73
      patients have been done. 3 variants of the colon position and anomalies of its
      fixation were distinguished. The methods of surgical correction of the colon
      position are recommended. 27 patients were operated on with positive results.

PMID- 8754903
TI  - [Diagnosis of chronic hemorrhage in diseases of the small intestine].
AB  - In a period of 10 years 38 patients received treatment in the clinic for iron
      deficiency anemia in whom the source of chronic blood loss was revealed in the
      small intestine. The radionuclide method for detecting concealed blood loss was
      most informative for the diagnosis (98%) of chronic intestinal hemorrhages, and
      was particularly important in cases with iron deficiency anemia of unclear
      genesis. Oral enterography was the most available method and sufficiently
      informative (32%) in the diagnosis of chronic hemorrhages from the small
      intestine. In 3-4 day, blood loss of more than 10 ml/24 h from the
      gastrointestinal tract verified by the radionuclide method but with the source of
      the bleeding not identified by instrumental methods, the indications for
      diagnostic laparotomy must be widened for careful examination of the small
      intestine.

PMID- 8754904
TI  - [Deep cystic colitis].
AB  - From 1970 to 1990 the authors treated 4 patients with deep colitis (DCC). There
      were 2 males and 2 females aged from 19 to 48 years (average age 28.7 years). A
      local form of DCC with involvement of the rectum (infero- and preampullar part)
      was recognized in all cases. The only method for DCC treatment is an operative
      intervention whose volume is determined by the form of the disease and the
      results of emergency intraoperative morphological study of the affected parts of
      the large intestine. All 4 patients underwent organ- and sphincter-preserving
      operation-transanal resection of the rectum. The postoperative period was
      uneventful. None of the patients had a recurrence of the disease in follow-up
      periods of 3 to 7 years.

PMID- 8754906
TI  - [Treatment of large recurrent strangulated inguino-scrotal hernias].
AB  - The study describes a group of patients with big recurrent strangulating inguino
      scrotal hernias. The age of patients was between 45 and 80 years. All of them
      were admitted to the hospital within first 12 hours after strangulation and
      underwent surgery. 11 patients had ordinary hernioplasty and 25 patients had
      autoperitoneal hernioplasty. This last method does not cause any trauma, it is a
      simple procedure and it does not take too much time. There were no deaths after
      operation. Recurrence of the hernia within a year after an operation was not
      reported. The function of a digestive tract is good after this operation.

PMID- 8754905
TI  - [Treatment of appendiceal peritonitis].
AB  - The results of treatment of 223 patients with acute appendicitis, complicated
      with advanced (51) and local (172) peritonitis have been analysed. Antibacterial
      treatment was conducted with account to the results of bacteriological analysis
      of the peritoneal exudate. Enterobacteria and non-spore anaerobic microorganisms,
      sensitive to the 2d and 3d generation cephalosporins, aminoglycosides and
      metronidazole, were prevailing. Non-use of abdominal drains and provisional wound
      sutures made it possible to decrease the duration of in-hospital period to 12.7
      days (15.4 days in general peritonitis; 11.8 days local peritonitis). The
      mortality rate was 0.4%.

PMID- 8754907
TI  - [Selective electroenterogastrography. I].
AB  - A new model of electroenterogastrograph has been designed. Besides of
      amplification it can divide the total bioelectrical activity into several flows,
      and distinguish potentials specific to the certain organ or its part. Each flow
      is depicted on a separate channel of the electroenterogastrograph. It makes it
      possible to increase the diagnostical value of the method. It is necessary to
      learn specific parameters of potentials of the organs to be tested. To register
      electrogastrogram it is necessary to use frequencies of 0.04-0.07 Hz;
      electroduodenograms 0.18-0.22 Hz, etc.

PMID- 8754908
TI  - [Assessment of the results of surgical treatment of lymphedema based on
      computerized tomography].
AB  - The possibilities of computed tomographic appraisal of the qualitative and
      quantitative characteristics of the soft tissues in lymphedema of the lower limbs
      were studied in comparison with the results of pre- and postoperative examination
      of 21 out of 86 patients with Stage II-IV lymphedema. There were 4 males and 17
      females, whose ages ranged from 16 to 41 years. In postoperative periods of 2
      weeks to 6.5 years 45 computed tomographic studies were conducted. It was shown
      that computed tomography is an objective basis for appraising the qualitative and
      quantitative changes in the soft tissues of the limbs in follow-up patients with
      lymphedema after creation of lymphovenous anastomoses. The examination confirms
      objectively functioning of the lymphovenous anastomoses after disappearance of
      supra- and subfascial edema and diminution and even normalization of the
      thickness of the subcutaneous fat.

PMID- 8754909
TI  - [Surgical tactics in spontaneous pneumothorax].
AB  - 219 cases of nonspecific spontaneous pneumothorax have been analysed. The bullous
      lung disease was the reason of pneumothorax in 55% of cases. Diagnostic and
      curative thoracoscopy is an important element of diagnosis. It was performed in
      45 patients. Surgical operations were done in 56 patients. An active surgical
      policy in the treatment of spontaneous pneumothorax is advocated. Partial and
      subtotal pleurectomy plays an important role in surgery, especially in diffuse
      bullous lung disease.

PMID- 8754910
TI  - [Local treatment of peritonitis by aspiration drainage].
AB  - Aspiration pelvic drainage in combination with naso-intestinal drainage were used
      in 783 patients with various forms of peritonitis. 489 patients had local
      peritonitis. There was no mortality in this group of patients. 294 patients had
      general peritonitis, the mortality rate in this group 6,5% (19 patients). In 34
      cases the re-do surgery has been performed (13 patients died). Aspiration
      drainage is recommended for the treatment of various forms of peritonitis.

PMID- 8754911
TI  - [Surgical treatment of insulin-dependent diabetes mellitus and its
      complications].
AB  - Free xenotransplantation of cryopreserved Langerhans cells (67 cases) and
      deportalization of pancreatic blood supply (37 patients) was done in 104 patients
      with insulin-dependent diabetes mellitus with positive effect. There were 58 men
      and 46 women at the age of 16-62 years. In 15 cases the combination of these two
      methods has been used that made it possible to enforce the antidiabetic effect
      and stabilize the development of diabetic complications.

PMID- 8754913
TI  - [Use of a distraction apparatus in complex treatment of osteoarticular paronychia
      and osteoarthritis of metacarpophalangeal joints].
AB  - Experience in the treatment of 41 patients with osteoarticular paronychia and 14
      patients with osteoarthritis of the metacarpophalangeal articulations is
      discussed. The treatment consists in arthrotomy, careful curettage of the tissues
      of the involved articulation and its through drainage, application of a primary
      suture to the wound, and application of a distraction apparatus. Graded
      distraction of the articulation ensures its decompression, which prevents
      progression of bone destruction and creates favorable conditions for regeneration
      of the articular ends, and prevents the formation of coarse cicatricial adhesions
      and ankylosis. All these measures make it possible to restore the function of the
      affected articulation.

PMID- 8754912
TI  - [Replacement of cervical vertebrae by carbon implants].
AB  - The cervical vertebrae were replaced by carbon implants in 60 patients; carbon
      synthetic foam was used in 19 of them and composite material based on carbon
      (ostec) in 41. The biological and mechanical properties of the implants ensured
      firm stabilization of the spine and excluded the danger of postoperative kyphosis
      and destruction of the vertebral bodies by the implant.

PMID- 8754914
TI  - [Tactics of surgical treatment of suppurative-necrotic lesions of the foot and
      leg in patients with diabetes mellitus].
AB  - Policy of surgical treatment of 200 patients with pyonecrotic lesions of the
      lower limbs and diabetes mellitus are analysed. The management of such patients
      should provide timely adequate surgical treatment of the focus of affection,
      correction of carbohydrate metabolism with increased doses of simple insulin,
      removal of intoxication, prevention of thromboembolic complications, and
      treatment of concomitant diseases. Necrectomy and drainage of the abscesses under
      epidural anesthesia are advisable in gangrene of the toes and phlegmon of the
      feet in patients suffering from diabetes mellitus. In the absence of a
      therapeutic effect amputation through the upper third of the leg is indicated.
      Amputation through the lower third of the thigh is indicated in phlegmon of the
      leg. But ketoacidosis must be completely relieved before the operation and the
      level of glycemia reduced to 12,0 mmol/l. Total mortality was 11%, postoperative
      mortality 8,5%.

PMID- 8754915
TI  - [Treatment of complications of plastic surgery on the tendons of finger flexors].
AB  - From experience in the treatment of more than 800 patients by various methods of
      autotendoplasty which had been developed in the clinic earlier, the authors
      analysed the most characteristic complications of these operations. Separation of
      the wound edges and partial marginal necroses of the skin occurred in 7-8% of
      patients, mainly in bilateral damage to the neurovascular bundles of the fingers,
      ligature fistulas in 6-7%, ruptures in 5%, flexion contractures of the fingers
      formed in 2% of patients who had been operated on, suppuration of the wounds was
      practically not encountered. The peculiarities of surgical sanative procedures
      for ligature fistulas depending on their localization are described. The
      operative tactics in rupture of the tendon sutures after tendoplasty was
      elaborated: immediate repeated autoplasty is recommended in late-term ruptures,
      whereas in early ruptures the best results are produced by two-stage tendoplasty
      with temporary endoprosthetics of the tendon with silicone no earlier than 2-3
      months after the rupture. The authors discuss the method for treatment of formed
      flexion contractures of the fingers by means of a distraction apparatus at a slow
      distraction mode, which produces good functional results.

PMID- 8754916
TI  - [Early postoperative acute cholecystitis].
AB  - Among the relatively rare complications occurring after various operations acute
      cholecystitis attracts particular attention. Its genesis is elucidated
      differently in the literature. In addition to the literature information
      discussed in the work, the authors, possessing experience in the treatment of 14
      patients with such postoperative cholecystitis, give a clinical characteristic of
      its manifestations and recommendations in respect to its early diagnosis and
      surgical tactics. The authors claim cholecystectomy to be the method of choice
      and, in extremely aggravated cases, decompression microcholecystectomy.

PMID- 8754917
TI  - [Repeated reconstructive operations in late complications of the aorto
      iliofemoral segment surgery].
AB  - The remote results of 220 reconstructing operations on an aorto-iliofemoral
      segment have been gathered in this article. The time for this analysis was from 1
      year till 5 years after an operation. There were 38.6% of late complications in
      the study. The atherosclerosis was the cause number 1 (70.7%), neointima
      hyperplasty was the cause number 2 (14.6%). We also have to mark technical
      problems (6.7%) and infectious complications (8%). 89 patients had repeated
      reconstructing operations after from 3 months till 5 years after the first
      operation. The blood circulation has been restored in 73% of cases. In 22.5% of
      cases it was necessary to make an amputation. The postoperative mortality was
      6.7% with the main cause of infection. The cause and the form of a complication
      were as important for the kind of an operation as the condition of an arterial
      vessels and a general patient's status.

PMID- 8754918
TI  - [Evaluation of the effectiveness of immunomodulators in the treatment of patients
      with postoperative suppurative-septic complications].
AB  - The influence of immunoactive medicines on the cell immunity have been studied.
      There were differences in reaction to T-activin and Thymalin between various
      patients with septic postoperative complications. Thymalin stimulated T-cells
      while acting with immunoglobulins or immune plasmas only. T-activin led to the
      increase in the number of T-lymphocytes and B-lymphocytes independently of it's
      cooperation with the vaccines. The stimulating effect of myelopid demonstrated
      itself by increase in the number of B-lymphocytes and immunoglobulins M and G
      after 14 days of treatment. The positive clinical effect was more impressive when
      immunomodulators were used in combinations with the vaccines; still it did not
      correlate completely with the dynamics of the cell immunity parameters.

PMID- 8754919
TI  - [Jet dissection of tissues in liver surgery].
AB  - The results of applying jet dissection in resections of the liver in experiments
      and in the clinic are discussed. The method is based on washing off the hepatic
      tissues with a high-pressure jet of liquid to expose the intact vessels and
      ducts. To realize the method, "A device for separating tissues of parenchymatous
      organs" was developed, which worked according to the principle of an injector
      without a needle. The efficacy and the degree of trauma inflicted by the method
      were tested in experiments, after which it was applied in the clinic in 14
      patients. The method made it possible to reduce essentially the volume of
      intraoperative blood loss, prevent the escape of bile in the postoperative
      period, reduce to the minimum hemotransfusion therapy, and shorten the stay of
      patients in the clinic. The results of jet dissection show the expedience of its
      use in surgical hepatology.

PMID- 8754920
TI  - [Method of laparoscopy in ventral hernia].
AB  - A new method of laparoscopy have been designed: a laparoscope is introduced
      through a ventral hernia. The method can be used in patients with
      contraindications for a regular laparoscopy. Umbilical hernia with the hernia
      orifice less than 3 cm is a contraindication for "herniolaparoscopy". The method
      was used in 32 patients, including 17 patients with the acute cholecystitis. In
      12 patients besides of umbilical hernia there were other contraindications,
      including postoperative scarring, obesity etc. There were no any complications
      with the use of the new method. In all cases pneumoperitoneum was preserved till
      the end of a procedure.

PMID- 8754921
TI  - [Successful treatment of giant hepatic hamartoma complicated by suppuration].

PMID- 8754922
TI  - [Surgical treatment of recurrence of insuloma].

PMID- 8754923
TI  - [Lymphangiosarcoma in the framework of marked arm lymphostasis after mastectomy
      (Stewart-Treves syndrome)].

PMID- 8754924
TI  - [Regression of 4th-stage cancer of the rectum].

PMID- 8754925
TI  - [Leiomyoma of the small intestine simulating retroperitoneal tumor].

PMID- 8754926
TI  - [Endoscopic laser destruction of gastric carcinoid].

PMID- 8754927
TI  - [Sipple syndrome (review of foreign literature)].

PMID- 8754928
TI  - [Primary hyperparathyroidism].

PMID- 8754929
TI  - [Treatment and prevention of acute embolic venous thrombosis].

PMID- 8754930
TI  - [An anniversary article on a non-anniversary date].

PMID- 8754931
TI  - [Role of Russian surgeons in the development of liver surgery (a centennial of
      the first liver resection in Russia)].

PMID- 8754932
TI  - HIV infection masquerading as Sjogren's disease: a clinical dilemma.

PMID- 8754934
TI  - What do they really think about us?

PMID- 8754933
TI  - Heart failure evaluation and treatment in Mississippi: results from a survey of
      the Mississippi Foundation for Medical Care. Heart Failure Study Group.

PMID- 8754935
TI  - National Advisory Committee on Immunization (NACI). Supplementary statement MMR
      vaccine and anaphylactic hypersensitivity to egg or egg-related antigens.
AB  - The fourth edition of the Canadian Immunization Guide (1993) recommends that
      "persons who have a history of anaphylactic hypersensitivity to hens' eggs
      (urticaria, swelling of the mouth and throat, difficulty in breathing or
      hypotension) should not be given measles vaccine except under special
      precautions." The precautions outlined include skin testing with diluted vaccine
      and graded challenge vaccination if the skin test is positive. Results of several
      recent studies have questioned such a cautious approach. NACI has reviewed all
      available data and revised its guidelines accordingly. The following revised
      guidelines are a major departure from the previously published recommendations.
      They will appear in the next edition of the Canadian Immunization Guide. A
      measles-rubella combination vaccine (Mo-Ru Viraten Berna TM) recently licensed in
      Canada contains no avian proteins and therefore can be used without regard to egg
      allergy.

PMID- 8754936
TI  - National Advisory Committee on Immunization (NACI). Interim advisory on measles
      revaccination of persons with acquired immunodeficiency syndrome (AIDS).

PMID- 8754937
TI  - The safety of immune globulins.

PMID- 8754938
TI  - Salmonella typhimurium infections in humans--United Kingdom.

PMID- 8754939
TI  - [An outline of chloro-organic compound toxicology].
AB  - Chloroorganic compounds, typified by the chlorinated aliphatic and aromatic
      hydrocarbons, especially biphenyls, naphthalenes, dibenzo-p-dioxins,
      dibenzofuranes and azo/xy/benzenes are, or were, manufactured as commercial
      products /the chlorinated biphenyls and naphtalenes/, and occur only as
      contaminants in commercial products /the chlorinated dibenzo- p-dioxins,
      dibenzofurans, and azo/xy/benzenes/. They have all become widespread in the
      environment. The chemical stability and lipophilicity of these compounds, and
      their resistance to degradation results in their persistence in the environment
      and concentration in the food chains. Their chemical structures are similar, i.e.
      they are approximate isostereomers. They act by the common receptor-mediated
      mechanism and produce similar toxic responses, although they vary greatly in
      potency. All classes of chloroorganic compounds have produced incidents of
      intoxication of industrial workers, the general population, and farm or wild
      animals. Chlorinated aromatic hydrocarbons elicit a numerous toxic effects which
      include body weight loss, thymic atrophy, immunotoxicity, hepatotoxicity and
      porphyria, chloracne and another dermal lesions, tissue-specific hypo- and
      hyperplastic responses, teratogenicity, reproductive toxicity, and
      carcinogenesis.

PMID- 8754940
TI  - [Toxicity of selected brominated aromatic compounds].
AB  - Flame retardants are added to plastic materials, textiles, wood, hydraulic
      liquids etc. for reducing their inflammability. These substances reduce the heat
      and carbon monoxide formation in case of fire. They are added in high amounts,
      even up to 30% of product mass (e.g. plastic material). The production of
      brominated flame retardants has been steadily rising in the last 20 years, e.g.
      in the 1990s the world production of polybromodiphenyl ethers (PBDE) reached
      40,000 tons annually. Mainly polybrominated flame retardants are produced, e.g.
      polybromobiphenyls (PBB), PBDE, hexabromobenzene (HBB). Their toxicity is low or
      nil, the DL 50 values are over 1 g/kg. However, when administered in low doses
      over longer time periods they can cause changes leading to porphyria. The
      information on the toxicity of polybrominated flame retardants for humans is
      derived mainly from the accident in Michigan, where PBB contamination of fodder
      for farm animals occurred with consequent contamination of food. In consumers of
      contaminated food cutaneous changes and neurological and muscular symptoms were
      noted. Polybrominated flame retardants can be metabolized and undergo
      biodegradation mainly trough debromination. The data on the toxicity of
      debromination products point to di- and tribromobenzenes, some of which are
      highly hepatotoxic. In acute poisoning hepatocellular damage manifest itself as
      necrotic changes in experimental animals receiving 0.1-0.8 of DL 50 of di- or
      tribromobenzene. After repeated administration of lower doses the hepatocellular
      damage assumes the features of porphyrogenic injury. In the environment
      polybrominated flame retardants can be transformed by various factors (high
      temperature during fire accidents, incomplete incineration of waste) to
      polybrominated dibenzodioxins of dibenzofurans whose lethal doses can in extreme
      cases be 0.001 mg for 1 kg body weight.

PMID- 8754941
TI  - [Biological and environmental monitoring of exposure to chlorinated aromatic
      hydrocarbons].
AB  - Polychlorinated hydrocarbons due to their lipophilic properties can cumulate in
      animal organisms by entering of various food chains. Food, especially of animal
      origin, is regarded as a major source of these compounds for man. For several
      years the Department of Environmental Toxicology of the National Institute of
      Hygiene jointly with sanitary epidemiological stations perform the monitoring of
      organochlorine compounds in food, including infant formula and breast milk. The
      results of this monitoring are presented in this paper. In order to assess the
      environmental exposure of man to organochlorine insecticides (DDT and HCH) and
      other contaminants i.e. PCBs and HCB were chosen. Samples were taken in 18
      voivodships in Poland. The results show that the exposure to above compounds from
      food of plant origin is negligible, and that the food of animal origin is the
      predominant source of intake of these compounds. The results of biological
      monitoring show that infants fed with breast milk are of greatest risk.

PMID- 8754942
TI  - [An attempt of health risk assessment for environmental exposure to chlorinated
      aromatic hydrocarbons].
AB  - An attempt has been made to assess the exposure of adult humans and infants to
      chlorinated hydrocarbons from food. Basing on the results from monitoring
      performed by the sanitary epidemiological stations in Poland the average
      concentrations of DDT, HCH, HCB and PCBs in variety of foods items were
      calculated. These average values were used as a base for the estimation of daily
      intake of polychlorinated hydrocarbons. For this purpose the average consumption
      of various groups of foods, including breast milk, were taken into consideration.
      The Estimated Daily Intakes (EDI) of the compounds were compared with the
      corresponding ADI values.

PMID- 8754943
TI  - [Evaluation of environmental exposure on persistent and toxic organic halogens].
AB  - The environmental concentrations of the persistent organohalogen compounds has
      been presented basing on the own results which were compared with the data
      published by the other authors. The predicted exposure of Polish population to
      PCDDs and PCDFs including combustion processes as a main potential source of the
      exposure has also been discussed. Analysis of the breast milk from Silesia region
      in Poland showed no substantial difference as compared to milk in other European
      countries.

PMID- 8754944
TI  - [Aromatic chlorinated hydrocarbons in in food of animal origin].
AB  - During 1990-1994 samples of fat tissues from about 18000 animals (swine, cattle,
      horses, rabbits, poultry and game animals), about 300 pooled milk samples and
      over 450 eggs were taken from the all 49 districts of Poland. Levels of
      organochlorine pesticides and polychlorinated biphenyls (PCB) were determined by
      capillary gas chromatography. The highest mean concentrations of DDT were found
      in fat of village hens (0.56 mg/kg) and fat of intensive rearing hens (0.2
      mg/kg). In swine, cattle and game animals these levels were 0.1 mg/kg and below.
      Other organochlorine pesticides (mainly HCH isomers and HCB) were found rather in
      low levels and only in some percentage of tested samples. Results of our 20 year
      study indicate that DDT levels in animal fat has decreased 20 times during that
      time. The highest mean concentrations of PCB were found in horses (0.08 mg/kg of
      fat) and from 0.02 mg/kg to 0.05 mg/kg in fat of other species, milk and eggs.

PMID- 8754945
TI  - [Problematic occurrence of chlorinated hydrocarbons in drinking water in Poland].
AB  - The reaction course in the development of trihalogenomethans /THMs/, the own
      results and those of Province Sanitary Epidemiological Stations obtained in the
      study of the content of volatile chlorinated hydrocarbons in tap water, and the
      possibility of preventing of excessive accumulation of these substances in water
      are discussed. There is still in Poland the danger of THMs present in
      unacceptable concentrations. For reducing the concentrations of THMs in drinking
      water it is necessary: to prepare water sources for the population according to
      the accepted regulations, to check repeatedly over long time periods the levels
      of THMs in drinking water, to changed the technology of water purification, to
      accept as obligatory demanding of opinions on the technology of water
      purification in the aspect of elimination of carcinogens.

PMID- 8754946
TI  - [Chloroform concentration in drinking water of the Lodz municipal area].
AB  - Chloroform is one the most important pollutants, formed in the process of
      chlorination of water from surface intakes. The city of lodz is supplied with
      water mainly from surface intakes containing considerable amounts of organic
      material and from deep water intakes. The aim of this study was to determine
      concentrations of selected organic compounds including chloroform in raw water,
      water after chlorination and on different stages of purification as well as in
      water introduced to the municipal water supply system. Chloroform was analysed in
      n-pentane extracts by gas chromatography with ECD. The detection limit of the
      analytical method was 1 microgram/l. Concentrations of chloroform in raw water
      were very low, in most cases below the limit of detection. As a result of
      chlorination level of chloroform in water increased reaching as high as 120
      micrograms/l. It has been shown that activated charcoal was not efficient in
      removing chloroform from water. Concentrations of chloroform were much lower in
      water from the municipal water supply system serving the northern part of town,
      where water from surface intakes was mixed with water from deep intakes.
      Concentrations exceeding 30 micrograms/l were determined only in the summer
      season. In both investigated parts of municipal water supply systems seasonal
      changes of chloroform concentration were observed with maximum values in June
      August. The concentration of chloroform in water samples collected in different
      quarters of town were strictly correlated with its concentration in treated water
      from the municipal water supply system serving the quarter.

PMID- 8754947
TI  - [Evaluation of mutagenic activity in water disinfected with chlorine].
AB  - City of Wroclaw is supplied with water from Olawa. The main contaminations of
      water are high concentration of organic compounds and bacteria count. Raw and
      drinking water show some mutagenic and carcinogenic properties in Ames tests. To
      improve the quality of drinking water now technology bored on infiltrated water
      composed of, coagulation, filtration and disinfection was tested. The goal of
      investigation and was to examine mutagenic and carcinogenic properties of raw and
      treated water. Potential carcinogenic activity of volatile disinfection-by
      products was estimated by direct analysis of THMs, while for nonvolatile
      halogenated organic substances Ames test was used. Carcinogenic risk based on
      THMs concentration could be estimate as 10(-5) for chlorine and 10(-6) for
      chlorine dioxide. Ozonation and post chlorination did not lowered the risk.
      Positives results of Ames test obtained for raw water no 2 with Salmonella
      typhimurium TA100, and for chlorinated treated water with Salmonella typhimurium
      TA98. The treatment of water with chlorine transforms same compounds into
      carcinogenic chlorinated derivatives and does not eliminate its harmful
      properties. Our results suggest that not all methods of treatment remove harmful
      to the health components from the water. Consequently in the case of the presence
      of such compounds in surface water it is necessary to employ appropriate methods
      and procedures the used Ames test allows rapid determination of the presence of
      carcinogenic compound in water. In Poland determination of the presence of
      potential carcinogens in water destined for the supply of urban areas is not
      obligatory and standard analyses of chemical composition do not give such
      information. It seems that the mentioned test could be considered for the control
      of the quality of raw and treated water as an indispensable measure contributing
      to reducing the health hazard for the population.

PMID- 8754948
TI  - [The effect of selected polychlorinated hydrocarbon pesticides on proliferation
      of cells in rat liver (14 day experiment)].
AB  - The aim of present studies was to describe the effect of two organochlorine
      pesticides: nuarimol and DDT on the changes in rat liver, proposed in the
      literature to be useful endpoints in screening of non-genotoxic hepatocarcinogens
      and/or liver tumor promoters. The effects on the following endpoints: mitogenesis
      (DNA synthesis and mitotic activity), hepatomegaly as well as histological
      changes in rat liver have been investigated. Male Wistar rats received nuarimol
      or DDT in one, five and fourteen daily oral administration of the doses of 125
      and 12 mg/kg b.w. day-1 respectively. In the case of both pesticides the effects
      observed consisted of hepatomegaly and hepatocyte proliferation (DNA synthesis
      and mitotic activity), although our studies indicated several distinct
      differences in the hepatic response between nuarimol, on the one hand and DDT on
      the other. The differences were reflected in the character and the basal rate of
      hepatocyte proliferation. Nuarimol elicited rapid but transient wave of
      hepatocyte proliferation during the first day of exposure. As opposite to
      nuarimol, DDT induced sustained hepatocyte proliferation during experimental
      period (14 days). Moreover, DDT induced evident focal necrosis and abnormal
      mitoses whereas nuarimol caused only slight vacuolated cytoplasm. Thus it can be
      concluded that nuarimol induced in rat liver direct mitogenic effect. On the
      other hand, DDT which is well known hepatocarcinogen, was found to produce
      mitogenic effect appearing to be related to regenerative response, since
      histological signs of necrosis were apparent.

PMID- 8754950
TI  - [Dioxins in the municipal waste incineration process--threats, norms, actual
      situation, counter-actions].
AB  - Within the group of organochlorine, posing a positive danger the natural
      environment, the most interesting, controversial and objectionable for ecology++
      are dioxins. In professional journals the name "dioxins" is a simplification
      which commonly refers to a certain group of organic chemical compounds, or, to be
      more precise, their derivatives called polychlorinated dibenzodioxins (PCDDs) and
      polychlorinated dibenzofurans (PCDFs). The latest research has confirmed the
      existence of yet another group of similar character polybrominated and
      polyfluorinated. Though other sources of industrial dioxins emission exist their
      first and foremost sources are incineration processes, in particular the
      processes of municipal, hospital and other toxic and chemical waste incineration.
      The compounds mentioned above, but all their isomers--tetrachlorodibenzodioxin
      (TCDD), tetrachlorodibenzofuran (TCDF)--are highly toxic and lack of emission
      control may prove highly hazardous for health and natural environment. The paper
      discusses a number of issues connected with dioxin emission during incineration
      of solid and gaseous municipal waste. A balance of the transport of dioxins
      between their source (i.e. the waste), through the process of their incineration
      and recombination, to the final stage--their presence in solid and gaseous
      incineration products. Following that European legislature on dioxin emission is
      discussed together with the presentation of state-of-the-art installations for
      reducing the amount of dioxins in exhausted gasses. Most of the research has been
      based on author's own observations and research done while taking active part in
      operation of selected waste incineration plants. The remaining data have been
      gathered from reference papers on current experiments carried out in European
      waste incineration plants. Summing up, the paper maintains that the incineration
      of municipal waste in state-of-the-art installations conforming to emission norms
      does not endanger the natural environment with dioxins emitted in exhaust gasses.
      This danger is, however, present in the solid incineration products due to high
      concentration of dioxins there. Operators are fully aware of this fact and
      attempt to counteract it. The awareness of presence of dioxins emitted in the
      process of waste incineration should be decisive factor while choosing technology
      and installation, which fitted appropriate cleanup equipment will guarantee level
      of dioxin emission safe for the environment and conforming to the norms of dioxin
      emission.

PMID- 8754949
TI  - [Dioxins--properties, occurrence and analysis problems].
AB  - Polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs)
      as well as similar compounds are described and characterized as a group of
      environmental pollutants which have been arousing interest only since a short
      time. The toxicity of the compounds in this group of xenobiotics is compared with
      that of other compounds generally regarded as highly toxic. The main sources of
      origin of PCDDs/PCDFs are found in nearly all fields of the technological actions
      of man. Problems of detection and identification of these compounds extremely
      difficult in analysis are discussed. These problems are a challenge to even
      specialist laboratories.

PMID- 8754951
TI  - [Effect of dioxin on health: use of chlorine in the United Kingdom].

PMID- 8754952
TI  - [Dioxins, furans, biphenyls and other chlor-organic compounds in breastmilk of
      women downwind of incinerators--a comparative study in Kehl/Strassburg].

PMID- 8754953
TI  - [Treatment of waste dumping site effluents using the wet photochemical oxidation
      method].
AB  - Sewage with high chemical requirements for oxygen /CRO/ and high content of
      halogenic hydrocarbons, e.r. effluents from dumping sites of ground waters with
      high content of polycyclic hydrocarbons can be purified with ozone alone or in
      combination with ultraviolet radiation or in combination with biological
      processing, UV and ozone. These methods enable the effluents to be processed
      properly from the ecological as well as economic standpoints, and the obtained
      values of CRO, CRO and WWA meet the requirements set down in regulations.

PMID- 8754954
TI  - [Diagnosis and treatment of chronic cough].

PMID- 8754955
TI  - [Use of thermographic methods for estimation of skin prick test results. II.
      Evaluation of skin prick test results with histamine solutions of different
      concentration using liquid crystal mixtures].
AB  - The aim of the study was to evaluate the usefulness of liquid crystal
      thermography in interpretation of skin prick tests with selected allergens and
      different solutions of histamine. The study group consisted of 35 young adults
      with indications for skin prick tests, and in whom skin tests with different
      solutions of histamine were also carried out (10 mg of histamine per 1 ml diluted
      to a concentration of 1:1, 1:10, 1:100). The skin reaction was assessed visually
      after 15 minutes, measuring flare and wheal diameter and utilizing the liquid
      crystal thermographic method--assessing the diameter of each colour green, blue,
      violet. For statistical purposes the area was also calculated. A correlation of
      each area was performed with the wheal and flare diameter. The area of the skin
      reaction was largest for both methods using the undiluted solution of histamine,
      the smallest using the 1:100 dilution. The liquid crystal thermographic method
      showed larger areas of skin lesions than those using only the visual method by
      analyzing the size of the wheal and flare. Due to this fact skin tests should be
      carried out at lest 9 cm apart from each other. The largest correlation was found
      between diameter of the flare and area of blue colour of the liquid crystal
      thermographic method (registering the temperature of 34.3 degrees C-36.3 degrees
      C). Using the thermographic method a joint temperature analysis of the wheal and
      flare lesions are performed. The results of this study correspond with the
      earlier, preliminary studies showing the usefulness of the liquid crystal
      thermographic method in assessing skin reactions to different allergens and
      histamine solutions.

PMID- 8754956
TI  - [Chemotactic serum activity for neutrophils and eosinophils and spontaneous
      production of histamine releasing factor in patients with seasonal bronchial
      asthma treated with nedocromil sodium].
AB  - Nedocromil sodium (NS- Tilade) is an effective therapeutic agent against asthma
      and has been shown to exhibit antiinflammatory activity in vitro. The aim of this
      study was to assess the effect of NS on the serum neutrophil (NCA) and eosinophil
      (ECA) chemotactic activity and mononuclear cells-derived histamine releasing
      factor (HRF) activity in 14 patients with seasonal allergic asthma. The
      chemotactic activities, HRF and bronchial reactivity to histamine (PC20H in
      mg/ml) were determined before the grass-pollen season and at the end of the 14
      day placebo treatment and 21-day NS treatment during the pollen-season. NCA and
      ECA were assessed using of the Boyden chamber methods. Blood samples for
      mononuclear cells culture were collected during the trial. The supernatants were
      assayed for HRF activity with basophils from a single donor. The NCA index was
      unaltered during the trial. There was a significant (p < 0.05) increase in the
      ECA after the NS treatment period (ECA index--2.5) compared with out of season
      and after placebo treatment (ECA index, 1.88 and 1.82). HRF activity increased
      after placebo compared with out of season (HRF % activity--38.62 before season,
      47.61 after placebo p < 0.05) but NS did not revealed the further effect on HRF
      activity (49.81 p > 0.05). During placebo the significant decrease in PC20H from
      1.81 mg/ml to 0.54 mg/ml (p < 0.05) was observed. NS did not have the effect on
      nonspecific bronchial reactivity--PC20H--0.74 mg/ml (p > 0.05). The correlation
      between PC20H and spontaneous production of HRF activity was not found. The
      results indicate that NS has some effect on inflammatory process which takes
      place in seasonal asthmatic patients during the natural allergic exposure.

PMID- 8754957
TI  - [Periodic breathing during sleep at high altitudes in patients with bronchial
      asthma].
AB  - Earlier we found that asthmatic patients treated at a high altitude sanatorium
      (3.200 m) had numerous episodes of arterial blood desaturation during the night.
      To investigate if periodic breathing (PB) was responsible for those episode we
      studied 5 asthmatics (A) (mean age 34 yrs) and 3 healthy controls (C) (mean age
      28 yrs) using MESAM 4, a simple, portable system recording breathing sounds,
      heart frequency, arterial blood saturation and body position. A and C subjects
      were first investigated at low altitude (760 m). There was no PB at 760 m in
      either group. At high altitude MESAM 4 recordings were performed on the 2nd and
      the 7th night after the ascent. On the 2nd night in the A group subjects the
      number of PB cycles averaged 37.2 (22-54) occupying 3.2% (2-5%) of estimated
      sleep time. The number of no-PB episodes was 52.4 (23-109). In the C group
      subjects the number of PB cycles was 83.6 (10-147) occupying 9% (1-14%) of
      estimated sleep time. The number of no-PB episodes averaged 45.6 (6-84). On the
      7th night in A the number of PB cycles was 46.6 (15-69) occupying 4% (1-7%) of
      estimated sleep time. The number of no-PB was 54.8 (13-147). In C the number of
      PB cycles averaged 29.3 (12-59) occupying 3.3% (2-6%) of estimated sleep time.
      The number of no-PB was 20.3 (9-37). We conclude that majority of desaturations
      during sleep in asthmatics at altitude of 3.200 m was not related to PB; the
      mechanisms of these desaturations require more investigations.

PMID- 8754958
TI  - [Ventilatory disturbances in school children with asthmatic symptoms in
      anamnesis].
AB  - In 102 school children aged 7 to 12 yr with diagnosed asthma or wheezing in the
      past 12 months spirometry was performed three times in 4 to 6 weeks intervals.
      Maximal expiratory flows at low lung volumes (MEF50 and/or MEF25) were reduced in
      more than one third of children. The reduction of MEF50 and MEF25 was more
      frequent, more deep, and more persistent in following tests as compared with
      FEV1%. Small airways obstruction was observed in almost 90% children with FEV1%
      slightly above limit value.

PMID- 8754959
TI  - [Evaluation of the usefulness of bronchoalveolar lavage for prognosing and
      monitoring the treatment of patients with chronic allergic alveolitis].
AB  - In 29 patients with chronic allergic alveolitis broncho-alveolar lavage BAL and
      lung function tests were performed before and after one year of Prednisone
      treatment. We observed significantly (p < 0.001) decrease of BAL lymphocytes from
      52% to 32% and significantly (p < 0.001) increase of BAL macrophages from 33% to
      54%. We found negative correlation between percentage of BAL neutrophils before
      treatment and annual changes of DLCO (r = 0.37 p < 0.05). Annual changes of
      lymphocytes negatively correlated with annual changes of DLCO (r = 0.45 p < 0.02)
      and D/VA (r = 0.46 p < 0.02).

PMID- 8754960
TI  - [Granulocyte-macrophage colony stimulating factor (GM-CSF) in material from
      broncho-alveolar lavage and serum of patients with bronchial asthma].
AB  - Granulocyte-macrophage colony stimulating factor (GM-CSF) is an important
      hematopoietic growth factor which has been shown to induce proliferation and
      activation of inflammatory cells and may play a role in allergic diseases. An
      activity of GM-CSF was determined in serum and BAL-fluid of 12 asthma patients
      with bronchial hyperreactivity to histamine before and 24 hours after challenge
      test. It was found statistically significant increase (p < 0.05) of GM-CSF
      activity in patients with bronchial hyperreactivity to histamine.

PMID- 8754961
TI  - [Bronchial asthma and chronic respiratory symptoms in the population of children
      in the Katowice voivodship--prevalence and risk factors].
AB  - Respiratory questionnaire survey in first grade students attending all public
      primary school in the city of Sosnowiec included 79.5% of all eligible children.
      In 1233 girls (G) and 1293 boys (B) the cumulative prevalence of chronic cough
      was: G - 17.5%, B - 20.8%, chest wheezing: G - 17.4%, B - 22.3%, and of attacks
      of dyspnea: G - 6.4%, B - 10.7%. Physician diagnosed asthma was found in 2.1% of
      girls and 3.4% of boys. The results of the logistic regression analysis showed
      statistically significant effects of sex and family history of asthma on all
      respiratory symptoms and diagnosis of asthma. Symptoms of chest wheezing depended
      also on environmental tobacco smoke and apartment density score (person/room). In
      relation to chronic cough the following additional risk factors were identified:
      place of birth in the Voivodship, hospitalization in the first month of life and
      breast feeding. A relatively low cumulative prevalence of childhood asthma in
      Sosnowiec, in comparison with the prevalence of epidemiological signs of
      asthmatic tendency, suggest that the magnitude of the problem of childhood asthma
      could be underestimated, if assessed only on physician diagnosed cases. The
      findings provide background information for further research on respiratory
      health in children living in the region of substantial ambient air pollution.

PMID- 8754962
TI  - [Diagnostic value of immunoglobulin E in serum of infants with spastic bronchitis
      and cow milk protein allergy depending on the method of examination].
AB  - We examined 83 infants suffering from spastic bronchitis and cow milk protein
      allergy and analyzed the diagnostic value of two allergic tests (Mancini, FAST)
      commonly used for measuring total IgE (t-IgE) level in serum. The aim of the
      study was to establish the sensitivity of these two methods. Our statistical
      analysis proved FAST test to be more sensitive than Mancini one (p < 0.01).

PMID- 8754963
TI  - [Bronchial hyperresponsiveness in patients with seasonal allergic rhinitis and
      the influence of loratadine and beclomethasone on this hyperresponsiveness].
AB  - 60 patients aged 16 to 46 years with seasonal allergic rhinitis were selected for
      study. Daily symptom scores of seasonal allergic rhinitis and nonspecific
      bronchial hyperresponsiveness to histamine (PC20H in mg/ml) before, during the
      pollen season and after 3 weeks of treatment with loratadine, beclomethasone
      dipropionate were evaluated. The control group received oxymetazoline.
      Nonspecific bronchial hyperresponsiveness for 11 patients (18.3%) before the
      seasons was observed. At the beginning of the season frequency of nonspecific
      bronchial hyperresponsiveness increased to 26.3% and to 36.8% after 3-week
      treatment course. Bronchial hyperresponsiveness was not related to any of the way
      of treatment. The patients treated with beclomethasone dipropionate and
      oxymetazoline showed significant relief of nasal symptoms. The patients without
      bronchial hyperresponsiveness showed lower value of symptom scores.

PMID- 8754964
TI  - [The influence of increased pressure in the pulmonary artery during exertion and
      evolution of pulmonary hypertension on survival of patients with COPD].
AB  - We aimed to investigate relations between PAP increase on exercise and long-term
      evolution of pulmonary hypertension and survival. 43 COPD pts were investigated.
      Initially they with mild pulmonary hypertension and abnormally high increase in
      PAP on exercise (40 W, 5 min). All pts were followed-up for 3-5 years. During
      follow-up 21 pts. died (group I), mean survival time was 28 +/- 17 month, and 22
      survived (group II), mean observation period was 59 +/- 22 month. Survivors were
      recatheterized after 3-7 yrs (mean 5 yrs). PAP increased by 3.4 +/- 4.9 mm Hg and
      correlated better with initial PAP (r = 0.91, p < 0.001) than with delta PAP on
      exercise (r = 0.61, p < 0.02). Survivors differed from dead in FEV1 (1.59 +/- 55
      vs 1.17 +/- 0.33 L, p < 0.02), VC (3.54 +/- 1.0 vs 2.8 +/- 0.84 L, p < 0.02),
      resting PaO2 (39.1 +/- 9.0 vs 46.3 +/- 11.5 mm Hg, p < 0.05) resting heart rate
      (82.5 +/- 13.6 vs 93.8 +/- 16.1 beats/min p < 0.02) resting PAP (20.7 +/- 8.2 vs
      32.3 +/- 13.2 mm Hg, p < 0.002), and resting PW (7.6 +/- 2.0 vs 11.6 +/- 7.4 mm
      Hg, p < 0.05).

PMID- 8754965
TI  - [Long-term corticosteroid therapy as a risk factor of osteoporosis in patients
      with asthma and chronic bronchitis].
AB  - This work evaluates frequency of steroid induced osteoporosis according to kind
      of steroid drugs (systemic, inhaled), dose and duration of treatment. In group of
      80 young patients with asthma and chronic bronchitis the following examinations
      have been used: biochemical markers of bone turnover, X-ray of thoracic lumbar
      part of vertebral column and bone density in quantitative computed tomography of
      vertebrae L2-L4. Osteoporosis appeared in patients chronically treated with
      systemic steroids (prednisone) and in patients treated with inhaled steroids in
      typical dose as well. Usefulness of biochemical markers of bone turnover in
      connection with quantitative computed tomography in diagnostic of steroid induced
      osteoporosis has been confirmed.

PMID- 8754966
TI  - [The effect of bronchial allergen provocation on spontaneous production of
      histamine releasing factor (HRF) by mononuclear cells in patients with bronchial
      asthma].
AB  - The study was performed in 8 patients suffering from mild asthma. Bronchial
      allergen challenges with Dermatophagoides pretonyssinus were performed according
      to Chai et al method. Nonspecific bronchial reactivity to histamine (PC20H in
      mg/ml) were determined before the allergen challenge and in 90 min. and 24 hrs.
      after allergen provocation. Blood samples for mononuclear cells culture were
      collected before the trial and after the allergen challenge in 15, 90 min. and 8
      and 24 hrs. The supernatants were assayed for HRF activity with basophils from a
      single donor. The significant increase of PC20H was observed xgPC20H in mg/ml
      0.43 before allergen challenge and 0.08 and 0.125 after allergen provocation.
      Blood samples did not reveal any significant changes in HRF % activity--mean and
      SD before challenge test 47.7 16.2 and 49.9 15.0 in 15 min, 53.3 19.0 in 90 min,
      56.6 15.8 in 8 hr, 52.5 20.4 in 24 hr after allergen provocation. The correlation
      between postallergen, nonspecific bronchial reactivity and spontaneous production
      of HRF activity was not found. The authors discuss the role of HRF in
      pathogenesis of nonspecific bronchial reactivity of asthmatic patients.

PMID- 8754967
TI  - [Hemangiopericytoma--rare lung tumor].
AB  - Hemangiopericytoma is a mesenchymal neoplasma, originated from pericytes---a cell
      type surrounding capillaries. Primary localization in the lung is especially
      rare. We report two cases of hemangiopericytoma of the lung with a completely
      different clinical outcome: one patient with an asymptomatic, peripheral lung
      tumor, 18 months disease-free after radical surgical therapy and another one with
      an advanced lung tumor, that infiltrated the pulmonary artery and caused distant
      pulmonary metastases. Based on the case report, possibilities and difficulties in
      the diagnosis as well as therapy of this rare primary pulmonary tumor are
      discussed.

PMID- 8754968
TI  - [Kartagener syndrome and hemangiomatous proliferation of lung capillaries: case
      report and literature review].
AB  - The authors present a case of Kartagener syndrome complicated by pulmonary
      hypertension accompanied by the lung capillaries haemangiomatous proliferation
      (post mortem diagnosis). Review of a literature (23 published cases) of the
      haemangiomatous proliferation of lung capillaries emphasizes clinico-pathological
      aspects and differential diagnosis. A rarity of Kartagener syndrome is another
      interesting point of a published case.

PMID- 8754969
TI  - [Congenital esophageal atresia with tracheo-esophageal lower fistula and
      infectious asthma complicated by severe status asthmaticus which required use of
      halogen ether inhalants--case report].
AB  - A five-year clinical study of a boy operated in the first day of his life due to
      esophageal atresia with tracheo-esophageal lower fistula has been presented, in
      whom severe endogenic asthma complicated by frequent status asthmaticus
      developed, which required application of inhalatory anaesthetics.

PMID- 8754970
TI  - [Nasal provocation tests].

PMID- 8754971
TI  - [Asthma and its treatment based on Polish source data from the end of the XVIII
      century].

PMID- 8754972
TI  - Neurons of the substantia nigra in the European bison.
AB  - The studies were carried out on the mesencephalons of four European bisons with
      two different Golgi procedures and stained according to the Nissl and Kluver
      Barrera methods. Four types of neurons were distinguished in the substantia nigra
      of the European bison. Type I are fusiform cells which are most numerous in pars
      compacta of SN. From each pole of the perikaryon originate 1-3 dendritic trunks.
      The axon arises from the base of dendritic trunk or directly from the lateral
      surface of the perikaryon. Type II are triangular cells which are most numerous
      in pars reticularis of SN. The neurons give off 3 primary dendrites. The axon
      arises mostly from the base of dendritic trunk. Type III are large multipolar
      neurons with 4-5 thick dendritic trunks. The axon emerges directly from the
      surface of the perikayon. Type IV are piriform and rounded cells. They have two
      thick primary dendrites, which leave the cell body at one pole of the neuron. The
      thin axon emerges from the cell body near the dendrites.

PMID- 8754973
TI  - Influence of fixation and histological procedure on the morphometric parameters
      of neuronal cells.
AB  - The influence of fixation and histological procedure on morphometric parameters
      of human and rat brains were analyzed. We found negative correlation of brain
      weight with the fixation time both in human and rat material. Human brains fixed
      for shorter period of time than one year showed large differences in weight. The
      group of brains fixed for longer than one year was characterized by much smaller
      dispersion. Moreover, we found that during histological preparation the shrinkage
      of brain tissue of older human subjects is statistically significantly smaller
      than younger ones (below 65 years). In order to correct these artifacts easily we
      propose three simple formulas.

PMID- 8754974
TI  - The peripheral part of the hypoglossal nerve in human embryos at stage 14 (32
      days).
AB  - The hypoglossal cord which is formed from occipital myotomes migrates rostrally
      to the future tongue. The hypoglossal nerve enters the hypoglossal cord which
      gives rise to the muscle of the tongue.

PMID- 8754975
TI  - External veins of the spinal cord it the Wistar rats.
AB  - In 54 Wistar rats the number, diameter, and topography of veins on the ventral
      and dorsal surfaces of the spinal cord were investigated. The spinal cord in rats
      possesses well developed venous net forming meningeal venous system. The veins
      pass independently of arteries and they consists of single trunks with intervals
      passing on the ventral and dorsal surfaces of the spinal cord as well as dorsal
      and ventral radicular veins draining to the epimeningeal venous plexus.

PMID- 8754976
TI  - Variants of shape of the pulmonary alveoli in corrosion casts in human lungs.
AB  - The shape of the pulmonary alveoli in pulmonary acini was investigated in
      corrosion casts and in translucent slices. Five types of the pulmonary alveoli in
      corrosion casts were distinguished. Most of them were spherical or saucer-shaped.
      In slices, made translucent in methyl salicylate, the pulmonary alveoli filled
      with the air were always spherical.

PMID- 8754977
TI  - Application of mathematical morphology in angiologic studies.
AB  - Application of mathematical morphology in morphologic sciences was tested. Two
      aspects were evaluated, cognitive and utilitarian on analyzing enigmatic objects
      in TK and searching for particular elements in angiologic photos taken in
      infrared. The results prove many application possibilities of the method.
      Combination of modern techniques: infrared, Pickworths method, TK, and image
      transformation delivers many new data. Mathematical morphology selects
      interesting details and rejects redundant information.

PMID- 8754978
TI  - Remarks on the structure and course of renal afferent glomerular arterioles.
AB  - In the material of 30 kidneys from corpses of adults of both sexes, the
      variations of ramification, course and structure of afferent glomerular
      arterioles in the superficial and juxtamedullary part of the renal cortex have
      been investigated using cleared preparation, histological, and SEM techniques.
      Within the afferent glomerular arterioles, two parts have been differentiated:
      the proximal, longer one, and the distal, shorter one. The afferent glomerular
      arterioles gave off branches draining directly to the peritubular capillary
      plexus.

PMID- 8754979
TI  - Remarks on the structure and course of renal efferent glomerular arterioles.
AB  - In the material of 30 kidneys from corpses of adults of both sexes the variations
      of structure and course of efferent glomerular arterioles in the superficial and
      juxtamedullary portions of the renal cortex have been described. The efferent
      arterioles of the glomeruli located in the superficial part of the renal cortex
      are short and after a short course they drained into the peritubular capillary
      plexus, whereas among the efferent arterioles of the glomeruli located in the
      juxtamedullary part of the cortex, two types have been differentiated: short and
      long ones, which demonstrated the variations of course, ramification and extent
      of vascularization.

PMID- 8754980
TI  - Communicating branch between the musculocutaneous and median nerves in human.
AB  - Communicating branch between the musculocutaneous and median nerves was found
      bilaterally in 1 human cadaver. The topography of vessels was normal.

PMID- 8754981
TI  - Distribution of venous valves in the great saphenous vein in human fetuses
      (preliminary study).
AB  - In six human fetuses the venous valves are present in the supragenicular portion
      of the great saphenous vein. The valves appear as delicate projections arranged
      perpendicular to the length of the vessel.

PMID- 8754982
TI  - The World Health Organization Cancer Pain and Palliative Care Program. Past,
      present, and future.

PMID- 8754983
TI  - Catalonia WHO Demonstration Project on Palliative Care Implementation 1990-1995:
      results in 1995.
AB  - A global, comprehensive, publicly planned and financed program to implement
      palliative care was designed by the Department of Health of Catalonia (6 million
      inhabitants. Planned in collaboration with the cancer unit of the WHO in 1989,
      the program was implemented in 1990-1995. It included specific services, measures
      general resources, education and training, organizational and educational
      standards, opioid availability, legislation and evaluation. The aims included
      coverage for cancer, AIDS, geriatric and other conditions, equity, quality,
      reference, and satisfaction for patients, families, and professionals. The
      results in 1995 include the implementation of 18 hospital support teams and 19
      Units, with a total of 350 beds, 42 home-care teams. The coverage for cancer and
      AIDS is around 40%, and 44/55 (80%) districts have a specific team. Palliative
      care implementation has been completely publicly financed, with a total yearly
      investment of 2,200 million ptas. Eighty percent of this has been saved through
      radical changes in costs and the pattern of the use of resources. Palliative care
      implementation has demonstrated efficacy in the care of the patients and
      families, efficiency in the provision of care, and cost-benefit in the regional
      global approach. It adds qualitative and organizational values to the health-care
      system. Its implementation must be prioritized and planned by the health
      administration, not only to improve the quality of care for advanced and terminal
      patients, but also to improve the global efficiency and appropriate use of
      resources in the public health system.

PMID- 8754984
TI  - Report of the European Association for Palliative Care.

PMID- 8754985
TI  - New international efforts to ensure availability of opioids for medical purposes.

PMID- 8754986
TI  - Development of the World Health Organization Guidelines on Cancer Pain Relief and
      Palliative Care in Children.
AB  - Assess pain regularly throughout the course of treatment. Follow the WHO
      Analgesic Ladder for selecting pain-relief drugs, that is, a stepwise approach to
      analgesic management, where a child's pain severity determines the level of
      analgesics. Use practical cognitive, behavioral, physical, and supportive
      therapies, combined with appropriate drug treatment. Administer adequate
      analgesics doses "by the clock," that is, at regular times, not PRN. Use oral
      routes for administering analgesics, and avoid painful routes of administration,
      whenever possible. Administer a sufficient analgesic dose to allow children to
      sleep throughout the night. Anticipate and treat side effects aggressively.

PMID- 8754987
TI  - Report from the International Association for the Study of Pain Task Force on
      cancer pain.

PMID- 8754988
TI  - Argentina: status of cancer pain and palliative care.

PMID- 8754989
TI  - Australia: status of cancer pain and palliative care.

PMID- 8754990
TI  - Chile: status of cancer pain and palliative care.

PMID- 8754991
TI  - Colombia: status of cancer pain and palliative care.

PMID- 8754992
TI  - France: status of cancer pain and palliative care.

PMID- 8754993
TI  - Germany: status of cancer pain and palliative care.

PMID- 8754994
TI  - Indonesia: status of cancer pain and palliative care.
AB  - Indonesia is a large archipelago with an estimated 203,000-365,400 new cancer
      cases a year. Most cases present in the advanced stage. Pain is the chief
      complaint in 89% of the patients of the palliative care unit at Dr. Soetomo
      hospital. The program is a community-based, family-oriented, and culturally
      adapted home care, widely applicable throughout the country. The service and
      medication should be affordable, simple, and available. The WHO three-step ladder
      has been adopted as the method of choice in cancer pain relief. Facilities
      supportive for the program are the existing health-care delivery system and non
      formal support system (Indonesian Cancer Foundation and Organization for Family
      Welfare Promotion, PKK). The chief constraints for program implementation are the
      geographical and population problems, lack of resources and funding for the
      training of health-care workers, and limited availability of oral morphine.

PMID- 8754995
TI  - Israel: status of cancer pain and palliative care.

PMID- 8754996
TI  - Japan: status of cancer pain and palliative care.

PMID- 8754997
TI  - Mexico: status of cancer pain and palliative care.

PMID- 8754998
TI  - People's Republic of China: status of cancer pain and palliative care.

PMID- 8754999
TI  - Republic of China: status of cancer pain and palliative care.

PMID- 8755002
TI  - The Netherlands: status of cancer pain and palliative care.

PMID- 8755000
TI  - Singapore: status of cancer pain and palliative care.

PMID- 8755001
TI  - The Philippines: status of cancer pain and palliative care.

PMID- 8755003
TI  - Turkey: status of cancer pain and palliative care.

PMID- 8755004
TI  - Uganda: status of cancer pain and palliative care.

PMID- 8755005
TI  - The nifedipine scare in hypertension: fact or fiction.

PMID- 8755006
TI  - Radiofrequency catheter ablation for AV nodal reentrant tachycardias (AVNRT).
AB  - Radiofrequency (RF) catheter ablation is the curative treatment of choice for
      atrioventricular (AV) nodal reentrant tachycardia (AVNRT). Analogous to the
      development of surgical techniques, catheter ablation has evolved from AV nodal
      ablation to selective "fast" and "slow" pathway ablation. "Slow" ablation is now
      the method of choice because of the lower incidence of associated AV block.
      Though slow pathway ablation can be achieved with equal success using either the
      anatomic or the electrogram-guided approach, fewer applications of RF energy are
      required for the potential-guided technique.

PMID- 8755007
TI  - Meta-analysis of coronary heart disease prevalence in India.
AB  - This meta-analysis was performed to determine the time-trends in the prevalence
      of coronary heart disease in India and age-and gender-specific changes. Inter
      study differences, urban-rural differences and age-and gender-specific
      differences were examined using the Chi-square test and Mantel-Haenzel Chi-square
      statistics for linear association. The prevalence of coronary heart disease
      increased from 1.05% in 1960 to 9.67% and 7.90% in 1995 in urban populations (X2
      = 277.5, p < 0.0001; Mantel-Haenzel X2 = 5.63, p = 0.018). In rural areas, the
      prevalence increased from 2.03% in 1974 to 3.7% in 1995 (X2 = 90.0, p < 0.0001;
      Mantel-Haenzel X2 = 2.94, p = 0.086). In urban areas there was a significant
      increase in the prevalence of coronary heart disease in men in the age groups 20
      29 and 30-39 years (p = 0.001) and in women in the age groups 20-29, 30-39 and 40
      49 years (p = 0.002). In rural areas the increase in men was in the age groups 20
      29 and 30-39 years (p = 0.001).

PMID- 8755008
TI  - Thrombolytic therapy in infants for femoral artery thrombosis following cardiac
      catheterisation.
AB  - Little information is available on the use of thromobolytic therapy in infants
      for femoral artery thrombosis after cardiac catheterisation. We report 12 cases
      (mean age: 4 months; range: 1-9 months) who received intravenous streptokinase
      (3000 U/kg bolus, 1000 U/kg/h) infusion. Five of them had undergone transarterial
      balloon dilatation procedures. Streptokinase was administered 48 h after
      catheterisation and continued for 4-20 h (mean 11.5 h). No detailed haematologic
      monitoring was done during therapy. Distal pulses were restored in all the
      patients. No complications were seen except a minor local ooze in two patients.
      We found that intravenous streptokinase is a safe and effective therapy for
      femoral artery thrombosis following cardiac catheterisation in infants.

PMID- 8755009
TI  - A ten-year post-surgical assessment of pulmonary hypertension in adults with
      patent ductus arteriosus.
AB  - The long-term follow-up was analysed for 25 patients above the age of 12 years
      who had patent ductus arteriosus with severe pulmonary hypertension and had
      undergone surgical closure. There were 11 males and 14 females (age range 12-27
      years; mean 18.6 years). There were 2 early and 2 late deaths. All the 21
      survivors were followed up at regular intervals for 8-10 years. They were
      assessed by haemodynamic study: 13 of the 21 survivors underwent a study 6 months
      to 1 year after surgery and another 4 patients, 8 years after surgery; 7 patients
      of the 13 had a second study 8-10 years after surgery. The pulmonary artery
      systolic and mean pressures regressed to 50% of the preoperative level in the
      first study for 15 patients, and in the second study 2 patients had further drop
      in pulmonary artery pressures; however, the pressure levels never reached normal
      values. The pulmonary vascular resistance did not show a correspondingly
      significant fall. In conclusion, the ten-year follow-up shows that the patients
      have benefited by the surgery though the pressures have not come down to normal
      levels, and that they have to be followed up closely to assess the natural
      history of residual pulmonary hypertension and pulmonary vascular disease and its
      effect on their quality of life.

PMID- 8755010
TI  - Morphologic and arteriographic changes in the pulmonary vasculature in children
      with congenital heart disease.
AB  - This study was undertaken to determine the morphologic changes occurring in the
      pulmonary vasculature in congenital heart disease. Autopsy was performed in
      twenty cases of congenital heart disease ranging in age from newborn (full term)
      to 14 years. Postmortem arteriography was performed in most of them followed by
      histomorphometry. It was found that medial hypertrophy of the muscular pulmonary
      arteries was the most consistent change and the smallest muscular arteries were
      the most severely affected. The lesions were focal and randomly distributed.
      Hence, morphologic observations on open lung biopsies may not be accurate.

PMID- 8755011
TI  - Cardiac tumours: an observational study.
AB  - We studied 38 patients with cardiac tumours. Of these, 30 had primary cardiac
      tumours while the rest had secondary tumours. The commonest manifestations in
      patients with primary tumours were exertional breathlessness (23), fever (9),
      mitral diastolic murmur (15), loud pulmonary component of the second heart sound
      (16), and mitral systolic murmur (21). Left atrial myxoma was the commonest
      diagnosis (24) followed by left ventricular leiomyoma (2), right atrial myxoma
      (2, one with RA and RV both), RV myxoma (1), and left ventricular haemangioma
      (1). The commonest modes of presentation of secondary cardiac tumours were atrial
      extrasystoles (5) and pericardial friction rub (4). Histopathological reports
      revealed bronchogenic carcinoma (4), breast carcinoma (2), seminoma of the testis
      (1) and lymphoma (1). The unexpectedly low number of secondary cardiac tumours in
      this series is attributed to the lack of routine autopsy studies in our
      institute.

PMID- 8755012
TI  - Automated on-line quantification of left ventricular ejection fraction by echo.
AB  - An automated border detection system based on the acoustic back scatter property
      of ultrasound has been recently developed. This provides beat-to-beat values for
      the left ventricular ejection fraction (EF). This study assesses the reliability
      of this method when compared with the angiocardiographic EF, and manual 2D-echo
      derived EF based on the modified Simpson method. Angiocardiographically-derived
      EF was used as the gold standard. In a total of 49 patients the
      angiocardiographic EF was found to be 64.49 +/- 15%. It showed excellent
      correlation with the automated border detection-derived EF (r = 0.91). The
      automated border detection-derived EF also showed excellent correlation with the
      manual 2D-echo method (r = 0.9). In addition, automated border detection requires
      less time than the manually drawn method (40.9 +/- 7.7 sec versus 58.6 +/- 7.5
      sec; p < 0.001). We conclude that the acoustic quantification of the EF
      correlates well with the angiocardiographically-derived EF and is less time
      consuming.

PMID- 8755013
TI  - Hypertension and CHD risk: whither alpha-1 blockers?
AB  - With the inclusion of alpha-blockers in the list of drugs recommended as
      firstline agents for managing hypertension, there has been a resurgence of
      interest in this group of drugs. The selective alpha-1 blockers reduce peripheral
      vascular resistance by blocking the alpha-1 receptors and preventing
      norepinephrine from reaching them. Their antihypertensive efficacy has been shown
      to be comparable to all other major classes of antihypertensive agents. They are
      also as well tolerated as the other currently used drugs, both facts being
      confirmed by the TOMHS. What differentiates them from the rest of the drugs is
      their beneficial effects on various other coronary heart disease (CHD) risk
      factors. While lowering blood pressure (a CHD risk factor by itself), the
      selective alpha-1 blockers also reduce serum total cholesterol and increase serum
      HDL cholesterol (yet another major CHD risk factor). These drugs have been shown
      to increase insulin sensitivity and lower blood glucose levels. In addition, they
      also cause regression of left ventricular hypertrophy. Given these added
      beneficial effects, the lipid- and glucose-friendly selective alpha-1 blockers
      are increasingly being used.

PMID- 8755014
TI  - Thrombotic occlusion of the left main coronary artery during stenting: successful
      management with intracoronary urokinase and autoperfusion balloon.

PMID- 8755015
TI  - Anomalous systemic venous connections in the absence of isomerism and major
      intracardiac anomaly.

PMID- 8755016
TI  - Utility of head-up tilt test in solving the dilemma of syncope.

PMID- 8755017
TI  - Percutaneous transluminal rotational atherectomy for treatment of in-stent
      restenosis.

PMID- 8755018
TI  - Ebstein's anomaly with coarctation of the aorta--an unusual association.

PMID- 8755019
TI  - Failure of electrocardiograph to diagnose right ventricular infarction in the
      presence of left ventricular infero-posterior infarction.

PMID- 8755020
TI  - Coarctation of the aorta: aortoplasty with Inoue balloon.

PMID- 8755021
TI  - Chronic constrictive pericarditis presenting as mass lesion in infancy.

PMID- 8755022
TI  - Idiopathic polymorphic ventricular tachycardia with normal QT interval requiring
      implantable cardioverter-defibrillator device.

PMID- 8755023
TI  - National PTCA Registry of India: data for 1995.

PMID- 8755024
TI  - Radiological evidence of pulmonary venous congestion in patients with and without
      right ventricular infarction.

PMID- 8755025
TI  - Complete heart block as a first manifestation of acute rheumatic fever.

PMID- 8755026
TI  - [The occurrence of micronuclei in generations of HeLa cells irradiated at low
      doses].
AB  - The frequency of cells with pronuclei was determined among the cells subject to
      acute and long-term treatment and their descendants. It remained unchanged after
      acute irradiation (60Co) at doses of 10-40 cGy but was elevated in three
      generations after long-term irradiation (137Cs, 20-40 cGy) and residence in the
      Chernobyl Nuclear Power Plant accident zone.

PMID- 8755027
TI  - [A comparative study of the action of 1-methyl-1-nitrosourea and 1,3-dimethyl-1
      nitrosourea on tumor cell DNA in vitro and in vivo by the alkaline elution
      method].
AB  - DNA damage of the tumor cells was studied by the method of alkali elution from
      filters after introduction of 1-methyl-1-nitrosourea (MNU) and 1,3-dimethyl-1
      nitrosourea (DMNU) to mice with Ehrlich ascites carcinoma or after treatment of
      the cultivated cells with these drugs. DNA was essay fluorometrically using DAPI.
      The degree of DNA damage was characterized by the constant of the alkali elution
      rate (Kae), which was estimated according to the anamorphism of the kinetic
      curves of elution. It was shown that in the case of MNU application the tumor
      cell DNA was damaged to a greater extent than in the case of DMNU application.
      Kae increased with the concentration of drugs. A correlation was established
      between the antitumor activity of the drug (kappa), K(ae), and the number of
      chromosome defects per cell (gaps, deletions, microfragments, ring chromosomes,
      and translocations). This suggests that kappa is due both to DNA damage and
      chromosome defects.

PMID- 8755029
TI  - [Cell sources, regulatory factors and gene expression in the regeneration of the
      crystalline lens and retina in vertebrate animals].
AB  - Over the past century extensive experimental materials have been accumulated
      concerning cell sources of lens and retina regeneration, successive
      transformations of the cells, regulatory factors, and gene expression during
      restitution of these eye structures. The use of nuclear and cytoplasmic markers
      provided convincing evidence that the removed lens is restituted from the dorsal
      iris cells in vivo or from embryonic cells of the pigment epithelium and retina
      in vitro. The removed or destroyed retina is restituted as a result of
      transdifferentiation of the pigment epithelium cells in amphibians, fish, birds,
      and mammals during embryogenesis, in larvae of some anuran amphibians, and in
      adult newts. Cell precursors of rods are a cell source of retina regeneration in
      adult fish. A subpopulation of randomly distributed cells, which are a cell
      source of rod formation during the normal development of the eye was found in the
      external nuclear layer with the use of electron microscopy and nuclear and
      cytoplasmic markers. These cells are not only a source of regeneration of rods,
      but also of cones and cells of the internal nuclear layer after destruction of
      the corresponding retina layers. There is a peripheral growth area in the retina
      of vertebrates, where multi- and unipolar cells are localized, which provide for
      the retina growth during ontogenesis. A paradox of retina regeneration consists
      in that these little differentiated cells are not a source of complete
      restitution of the removed or destroyed retina. They make only a small
      contribution to its regeneration corresponding to the growth potential of cells
      of this eye region, while restitution of the retina proceeds only at the expense
      of cells of another type of differentiation. A factor controlling the
      differentiated state of the cell was found in the dorsal iris during studies of
      lens regeneration. Removal of this factor in the early stages of cell
      transformations leads to the initiation of lens regeneration. The factor is not
      specific and was identified in many cells of vertebrates, including the pigment
      epithelium and limb tissues, which, as is known, may be fully restituted. Studies
      of gene expression during lens and retina regeneration are now at the initial
      stage. The greatest advances were achieved on the model of transdifferentiation
      of the pigment epithelium cells of chick embryos into lentoids. Expression of
      genes MMP115 and pP344 was established in the pigment epithelium cells, which
      characterize the pigmented phenotype of the initial cells. Expression of the
      alpha-, beta-, and delta-crystallin genes was found in the lentoids, which
      characterize the phenotype of regenerating structures. The gene activity appears
      to be switched at an intermediate stage during cell dedifferentiation. Expression
      of the gamma-crystallin genes during lens regeneration in adult newts is
      initiated after completion of dedifferentiation and cell proliferation in the
      dorsal iris. The genes specifically expressed in the dorsal and ventral iris and
      in the retina rudiment have been identified by the method of gene subtraction.
      Expression of homeobox-containing genes from the family of PAX genes was found
      during lens regeneration in adult newts and retina regeneration in adult fish.
      The role of growth factors (FGF) as morphogenetic factors was proved, which are
      involved in a yet unknown way of altering the differentiation pathway of the
      initial cells during formation of the neuroepithelium rudiment in chick embryos,
      adult newts, and fish.

PMID- 8755030
TI  - [The discovery of new internal sources of neural retinal regeneration after its
      detachment in newts. Morphological and quantitative research].
AB  - A model of experimental detachment of the retina in adult newts Pleurodeles waltl
      was used for studies of internal sources of the neural retina regeneration.
      Changes in morphology, localization, behavior, and abundance of the cells of
      various retinal layers were studied on serial semithin and ultrathin sections of
      the retina taken at different times after the operation. As a result, a new class
      of cells was found in the external nuclear layer, which differ from the
      photoreceptors but have a certain morphological similarity with the bipolar cells
      in the internal nuclear cell layer that have a Landolt's club. These cells were
      called bipolar-like cells. The bipolar-like cells, which amount to 10-12% of the
      cells in the external nuclear layer, proved to be capable of producing new
      photoreceptors during retina recovery after its detachment. We propose that the
      bipolar cells with Landolt's club of the internal nuclear layer that are
      displaced towards the sclera after the death of a part of the photoreceptors are
      a source of the bipolar-like cells of the external nuclear layer. Supposedly,
      they are also a source of neuroblasts that we first found at later stages after
      detachment in the case of more intense destruction of the retina nuclear layers.
      The neuroblasts arising in the internal nuclear layer are displaced apically and
      divide to form radial "inserts", whose cells differentiate and restore the cell
      composition of all three nuclear layers of the detached retina. The discovered
      internal sources of regeneration of the neural retina in newts are compared with
      those known in fish, precursor cells of rods, and the role of other cell types in
      the retina regeneration is described under the given conditions of its damage.

PMID- 8755028
TI  - [The molecular mechanisms of the action of the radioprotector indometafen. The
      biosynthetic and bioenergetic aspects].
AB  - It was shown that indomethaphen (IM) is capable of stimulation of the synthesis
      of DNA, RNA, and protein precursors in mice. The IM-induced elevated level of the
      ribonucleotide reductase activity and, hence, deoxyribonucleotide pool in the
      spleen at the moment of irradiation and during the early postradiation period
      provides for complete DNA repair. As a result, the damaging effect of ionizing
      irradiation is weakened. At later stages (2-20 days) IM activates protein and DNA
      synthesis leading to the recovery of the ribonucleotide reductase activity in the
      spleen, on increased content of Fe3(+)-transferrin, cytochrome-c-oxidase, and
      ferrosulfuric components of the mitochondrial electron transport chain, and
      increased potential of the detoxication system due to the elevated content of
      cytochrome P-450. IM stimulates ATP synthesis. Thus, IM enhances compensatory
      restorative reactions of the cell systems, more pronounced in the spleen than in
      the liver.

PMID- 8755031
TI  - [The binding of [3H]aldosterone by brain corticosteroid receptors in rats with
      different individual-typological behavioral characteristics].
AB  - [3H]Aldosterone (AS) binding to cytoplasmic corticosteroid receptors (CR) of the
      hippocampus and brain (without cerebellum and hippocampus) was studied in rats of
      two behavioral types under normal conditions and within two weeks after electric
      pain stress. No asymmetry was shown in the distribution of CRs that bound [3H]AS
      in the rats of both groups. A relationship was established between the hormone
      binding by CRs of the hippocampus, rather than the rest of the brain, and type of
      animal behavior. The action of the stress factor led to decreased binding of
      [3H]AS to CRs of both hippocampus and brain. Thus, a relationship between the
      state of CRs of the hippocampus and individual behavior of animals was first
      established. The results obtained agree with the published data on relationship
      between the emotional reactivity of the animals and state of CRs in the limbic
      structures of the brain.

PMID- 8755033
TI  - [Micro vs. macro: structural-functional organization of avian micro- and
      macrochromosomes].
AB  - Karyotypes of lower vertebrates mainly consist of microchromosomes. In higher
      vertebrates, microchromosomes are present in each class of the most primitive
      orders. Birds have more microchromosomes in their karyotype than other
      vertebrates. Accumulation of microchromosomes in the avian karyotype probably
      occurred after separation of birds from reptilians in Triassic, but prior to
      radiation of ancestors of the modern orders (late Cretaceous-early Jurassic). In
      this review, the structural, molecular, and functional organization of avian
      macro- and microchromosomes and their participation in genetic processes are
      discussed. The average size of an avian microchromosome is about 12.4 Mb, which
      is ten times less than the size of an average macrochromosome. In contrast to
      macrochromosomes, medium and small avian chromosomes lack the highest level of
      chromosomal organization: their chromonemes do not have spiral coiling.
      Microchromosomal euchromatin largely consists of GC-rich R regions. More than
      half of the mapped avian genes are located on microchromosomes. Crossing-over
      frequency in microchromosomes is approximately threefold higher than in
      macrochromosomes. This may be caused by high GC content and recombination hot
      spots, which are present on each microchromosome. High recombination frequency in
      microchromosomes increases the probability of their correct meiotic segregation.

PMID- 8755032
TI  - [A trial of the efficacy of using the synthetic antioxidant dibunol in the
      chemotherapy of experimental tumors].
AB  - We studied the therapeutic efficiency of the synthetic antioxidant Dibunol alone
      and in combination with cytostatic drugs on animals with experimental tumors
      after simultaneous and successive administration. Introduction of Dibunol to
      animals (tumor carriers) soon after the transplantation of tumor cells had
      adverse consequences, stimulated tumor growth and reduced the life span of
      animals. Dibunol exerted a therapeutic effect only in cases of developed tumors.
      Simultaneous introduction of cytostatic drugs (cyclophosphamide,
      dimethylnitrosourea, ADEKO) and Dibunol to tumor carriers was efficient and
      increased the mean life span of animals. The antitumor effect of the
      cyclophosphamide-Dibunol combination did not, in practice, depend on the interval
      between introductions of these drugs. However, the mean life span and survival of
      animals were somewhat higher the intervals between introductions or simultaneous
      application of the drugs were short.

PMID- 8755034
TI  - [Genomic imprinting as a universal mechanism of gene function in development].
AB  - The term genomic imprinting is used to designate the phenomenon of functional
      nonequivalence of alleles whose activities depend on their parental origin. A
      functional hemizygosity of the gene is characteristic for genomic imprinting.
      However, activities of alleles also depend on their parental origin in some cases
      of diallelic gene expression. These cases are described in the literature as
      possible examples of imprinting. In this paper, different manifestations of
      genomic imprinting are analyzed, and a hypothesis is suggested about the murine
      genome as a set of genes with different expressions of homologous alleles, whose
      activities depend on their parental origin.

PMID- 8755035
TI  - [The unstable system sn(49) in Drosophila melanogaster: results of blot
      hybridization and polymerase chain reaction].
AB  - A set of 40 strains of alleles of different phenotype and mutation frequency,
      derived from unstable system sn49 of Drosophila melanogaster, was obtained. A
      mutation in the singed gene or the formation of a visible de novo mutation in the
      studied X chromosome served as the criterion for strain isolation. Total DNA was
      isolated from the obtained strains and used for blot-hybridization and polymerase
      chain reaction (PCR). Rearrangements were found within the first intron of the
      singed gene. In the first intron of an allelic derivative of this unstable
      system, an inserted sequence of at least 4 kb in length was found. Using PCR
      primers from this intron, fragment length polymorphism in different derivatives
      was revealed.

PMID- 8755036
TI  - [Cloning of the tag7 gene expressed in metastatic mouse tumors].
AB  - Gene expression was compared in a metastatic (VMR-Liv) neoplastic cell line and a
      related nonmetastatic (VMR-O) neoplastic cell line by means of the differential
      display method. A fragment of cDNA corresponding to the tag7 gene, differentially
      expressed in the metastatic cell line, was isolated. The full-length tag7 cDNA
      was cloned and its nucleotide sequence was determined. No homology between the
      tag7 gene and known sequences was revealed. tag7 gene transcription was studied
      in some tumors, cell lines, and normal mouse organs.

PMID- 8755037
TI  - [Characteristics of spontaneous mutagenesis in haploid yeast].
AB  - The dynamics of appearance of spontaneous revertants was studied in haploid
      strains of Saccharomyces cerevisiae, auxotrophic for adenine or leucine.
      Mathematic models of this process were used. It was confirmed that in the case of
      adenine auxotrophs, an increase in the number of revertants, depending on
      decreasing adenine content, was caused by a change in mutation rate of the ade2
      gene. For leucine auxotrophs, a similar phenomenon was determined by an increase
      in the rate of appearance of Leu+ revertants due to a decrease in size of initial
      auxotrophic cell colonies. Alteration in leucine content in the medium from 3 to
      300 mg/l did not lead to a change in the reversion rate for the leu2 gene. The
      heterogeneity of revertants detected at different times was described.

PMID- 8755038
TI  - [Effect of genetic background on mutation frequency of insertional alleles of the
      lozenge in Drosophila melanogaster].
AB  - We studied the effect of genetic background on mutation frequency of an unstable
      lz75V allele of the lozenge gene (lz; 1-27.7) isolated from natural populations
      of Drosophila melanogaster and its mutant derivatives lzB abd lzsl. Genetic
      composition of the X chromosome containing unstable alleles (X75V chromosome) was
      shown to affect their mutability. The region of the chromosome proximal to
      lozenge contains factors required for high mutability of lz75V and lzB.
      Substitution of a distal part of the X chromosome from a laboratory strain for a
      homologous part of the X75V chromosome also resulted in stabilizing lz75V, but
      caused an increase in mutation frequency of lzB. Association between instability
      of lz75V and the presence of P element with the locus was revealed by in situ
      hybridization. Studying effects of regulatory elements from a pi 2 P strain
      showed that the P cytotype is associated with a twofold to threefold decrease in
      mutation frequency of lzB and lzsl, but P-M hybrid dysgenesis is associated with
      its slight increase. Regulation of instability of the lozenge gene within the
      X75V chromosome was assumed to involve three levels: (1) character and topography
      of a mobile element inserted into the locus, (2) regulatory factors of other X
      chromosomal regions, and (3) cytoplasmic factors. The results obtained are
      discussed in terms of regulation of transposition of mobile genetic elements.

PMID- 8755039
TI  - [Genetic features of the Brown Carpathian breed--a vanishing local breed of
      cattle in the Western Ukraine].
AB  - A wide range of variation in immunogenetic and biochemical markers was found in
      thoroughbred Brown Carpathian cattle. Comparative analysis of genetic structure
      of Brown Carpathian and Swiss cattle, as well as various hybrids of these two
      breeds, with respect to polymorphic biochemical systems, demonstrated that all
      hybrids having any gene admixture of the Brown Carpathian breed formed a single
      cluster in a dendrogram and were readily distinguishable from thoroughbred Swiss
      cattle. Originally, the Swiss breed participated in forming the gene pool of
      Brown Carpathian cattle. The selective advantage of some gene associations, which
      included the loci of the biochemical genetic systems studied, was suggested to be
      a specific characteristic of the Brown Carpathian breed. Genetic differentiation
      in the groups of hybrids bred in regions with different ecological conditions
      (high- and lowland) was revealed.

PMID- 8755040
TI  - [Genetic structure of the Pinzgauer breed in the Carpathian region].
AB  - Phenotypic and genotypic characteristics of groups of Pinzgauer cattle bred at
      lowland, highland, and alpine farms in the Carpathian Mountains were studied. A
      high variation of the cattle with respect to blood groups was revealed. It was
      found that the genetic structure of the highland group of Pinzagauer cattle was
      somewhat similar to that of Brown Carpathian cattle with respect to biochemical
      genetic systems, mainly transferrin and amylase-I loci. It is thought that the
      similarity found may be accounted for by close ecological and geographical
      breeding conditions of the groups of cattle studied.

PMID- 8755041
TI  - [Effect of hereditary factors on tolerance for surgical treatment in patients
      with lung cancer].
AB  - Genetic polymorphism at 10 independent loci (ABO, RH, HP, GC, PI, TF, ACP1, PGM1,
      GLO1, and PTC) was studied in male patients with lung squamous cell carcinoma.
      These patients were divided into two groups, depending on their tolerance for
      surgical intervention and on the postoperative course: (1) patients with an
      uneventful postoperative period and (2) patients with postoperative
      complications. The genetic structure of the combined sample at the loci studied
      did not differ from that of the control group consisting of health people
      (population control). Genotypic differences might manifest at the postoperative
      stage rather than at the onset of the disease, and determine the presence of
      postoperative complications. However, comparative analysis of the two groups of
      patients revealed their polar divergence in respect to phenotype and gene
      frequencies at certain loci. Moreover, the genotypic structure of patients in
      both groups differed from that in the combined sample and in the population
      control. In the group with postoperative complications, higher frequencies of the
      alleles GC*1F, ACP1*A, and HP*2 were observed. By contrast, the group of patients
      with an uneventful postoperative period demonstrated prevalence of the
      alternative alleles of these loci: GC*2, ACP1*B, and HP*1. The greatest
      difference in the distribution of informative allele frequencies was observed
      between the group of patients with postoperative complications and the control
      group. This is evidence that these groups significantly differ in their genetic
      structure. Such divergence is largely determined by the polymorphic
      multifunctional systems of serum proteins.

PMID- 8755042
TI  - [Monogenic hereditary diseases in Gorno-Mariiskii district of Marii El republic].
AB  - The population of Gornomariiskii raion, Marii El Republic, primarily made up of
      mountain Marii, was subjected to medical genetic examination. The size of the
      entire population is 54853. Estimates of hereditary pathology in urban and rural
      populations of the raion were obtained. They were 0.68 and 1.11, respectively,
      for autosomal dominant pathology (AD); 0.55 and 0.81 for autosomal recessive
      pathology (AR); and 0.45 and 0.20 for X-linked pathology. Twenty-two, 25, and six
      nosologic forms of autosomal dominant, autosomal recessive, and X-linked diseases
      were revealed, respectively. We attempted to compare the sample under
      consideration with previously studied Russian and Finnish populations for rare
      pathologic recessive genes.

PMID- 8755043
TI  - [Criterion quality and estimation of the expected sample size in sequential
      analysis of linkage].
AB  - It is shown that, when conducting sequential testing of linkage in pedigree
      samples, (1) type I and type II errors observed are less than expected and (2)
      the generally accepted method for determining the average sample size, E(N),
      required for sequential analysis of linkage, underestimates it. A less biased
      approximation of E(N) is proposed. A wide scattering of actual sample sizes
      required for completion of sequential analysis is demonstrated, which puts
      practical use of E(N) into question.

PMID- 8755044
TI  - [A vector model of the simultaneous contrast of achromatic stimuli].
AB  - The vector model of simultaneous brightness contrast for achromatic colours is
      suggested. The difference of intensities between the test and inducing fields is
      evaluated in subtracting neurons. The difference is added to the test field
      activation if the intensity of the latter is greater than that of the inducing
      field and is subtracted under the opposite conditions. The lightness of the test
      field is coded by a two-dimensional vector which is composed of excitations of
      white and grey or black and grey neurons. Single values of lightness are coded by
      selective lightness detectors.

PMID- 8755045
TI  - [The effect of set on human cognitive activity].
AB  - A psychological set was formed in 30 healthy adult subjects by means of
      successive exposition on the screen (with the intervals in 3-7 sec) of 30 single
      pseudo words written in the Latin letters. This series of stimuli was immediately
      followed by similar presentation of 36 single Russian words which consisted of
      the letters written in the same way as some characters of the Latin alphabet. At
      the beginning of the second train of stimuli all the subjects began to read the
      well-known Russian words as senseless. In 11 subjects this effect disappeared
      after 1-2 Russian word presentations and in 19 subjects only after 6-36
      presentations. Analysis of the reaction time to the presentation of the visual
      probe stimulus suggests that the formation of preparatory set improves selective
      attention to the stimuli acting in a given situation and thus consolidates the
      cognitive processes.

PMID- 8755046
TI  - [The functional organization of the cerebral hemispheres during directed
      attention in children 7 to 8 years old].
AB  - Functional organization of brain hemispheres of 15 right-handed 7-8-years-old
      children was analysed during attention directed to the classification of
      lateralized auditory and tactile stimuli according to their duration. The
      subjective task difficulty was equal for all the children. Random presentation of
      stimuli in series of right and left-side stimulation and visual indication of the
      forthcoming stimulus modality (warning signal) improved the direction of
      subject's attention in accordance with the instruction. Monopolar EEGs were
      recorded from 15 cortical leads in both hemispheres referenced to linked ear
      lobes. EEG spectral analysis was performed with assessment of spectral power
      density and coherence of the alpha-range components. The hemisphere dichotomy
      which had been revealed in adult subjects under the same conditions was shown to
      be absent in children. Local functional integration of cortical regions around
      the modality-specific areas (T3, T4 for the auditory and C3, C4 for the tactile
      stimulation) was found in both hemispheres of children in contrast to the only
      left hemisphere in adults. The diffuse, modality-independent functional
      organization of adult right hemisphere was not observed in children. The
      described features of intrahemispheric organization in both groups provide
      correct decisions thus characterizing the successful alternative strategies. The
      grounds of revealed age differences, age-dependent mechanisms of functional
      hemisphere organization, and nonlinear trend of hemispheric specialization
      development are discussed.

PMID- 8755047
TI  - [The resonance EEG reactions in rhythmical photostimulation and the changes in
      functional status].
AB  - Changes in EEG fine structure in the occipital areas, heart rate, and breath
      pattern were recorded in 10 male volunteers under photic stimulation with slowly
      varying frequency in the range of lower or higher EEG alpha-subbands. Self
      ratings (on the scale SAN-self-assessment of state of health, activity, and mood)
      of the functional state, general activity, and mood were obtained before and
      after stimulation. EEG effects of such photostimulation were represented by the
      resonance EEG responses of discrete spectral EEG components, frequencies of which
      periodically coincided with varying rate of flashes. Resonance alpha-enhancement
      levels depended on the initial individual EEG alpha-voltage and stimulation
      frequency. Average changes in objective and subjective parameters did not differ
      between the conditions of lower and higher frequencies of stimulation but were
      significantly different and of opposite signs when the subjects gave higher and
      lower self-ratings of positive stimulation effect regardless of the stimulation
      frequency.

PMID- 8755048
TI  - [Differences in the the EEG frequency characteristics during the perception of
      positive-emotional, negative-emotional and neutral words].
AB  - Power spectral analysis of the theta- and alpha-rhythms was performed in narrow
      frequency bands (1 Hz) for EEGs recorded from F3, F4, C3, C4, T3, T4, P3, P4, O1,
      and O2 derivations in 9 healthy adults viewing emotionally positive, negative,
      and neutral words displayed on the screen. The relative spectral power in the 7-8
      Hz band was higher during presentation of the emotionally significant words than
      the neutral ones. The EEG reaction to emotional words within this frequency range
      depended on the word valency. The relative power increase was revealed in the
      range of 7-7.5 Hz during presentation of emotionally positive stimuli. This
      reaction was most expressed in the frontal, central, and temporal cortical areas.
      During presentation of the negative words similar EEG reactions were observed
      within 7.5-8 Hz. In this case the frequency changes dominated in symmetrical
      frontal, right central, temporal, and parietal cortical areas.

PMID- 8755049
TI  - [A comparison of the restructurings in the spatial-temporal organization of the
      cortical potentials from the human cerebral hemispheres with the EEG frequency
      characteristics during the solving of a cognitive task].
AB  - Spectral characteristics of the local and global EEG spatial-temporal
      organization were studied in 10 healthy subjects during solving the complicated
      intellectual tasks. Techniques of evaluation of successive topograms and point
      frequency mapping were applied. Two different types of the global spatial
      temporal organization of brain potentials were observed. Increased delta in EEG
      spectra characterized the task solving. The alpha- and beta-rhythms occupied the
      limited part of the cortex. Point mapping enabled clarification of the spatial
      distribution of the dominant spectral frequencies and their redistribution under
      different functional loads. Comparison of the characteristics of the spatial
      temporal organization of global bioelectrical processes and maps of the dominant
      rhythms in EEG power spectra made it possible to reveal the new relations in
      bioelectrical processes.

PMID- 8755050
TI  - [Changes in the components of the human visual evoked potential during
      conditioning using biological feedback].
AB  - The VEPs to checkerboard-flashes were recorded from Cz in 32 healthy adult
      volunteers (14 men, 18 women) under biofeedback conditions. The subjects were
      instructed to modify N100-P200 component in such a way that the amplitude of the
      segment within selected time-window from the beginning of the sample to its main
      positive peak exceeded the definite threshold. Each subject solved the task by
      means of individual combination of voltage and temporal regulation with the
      prevalence of the latter. Shifts of the latencies both of N100 and P200 were
      involved in VEP modifications. Four groups of subjects were distinguished by
      their success in task performance which depended on the strategy and level of
      self-estimated tiredness. The latency of N300 (out of the chosen time-sample) was
      longer for the subjects which were successful in increasing the number of
      "correct" responses. Differences in VEP components depended on the strategy
      types, levels of self-estimated tiredness, and sex on the subjects.

PMID- 8755051
TI  - [An evaluation of the differences in human evoked cortical potentials to visual
      stimuli].
AB  - Analysis of evoked electrical activity reveals periodically appearing differences
      in human visual evoked responses. These differences can be detected with an
      interval approximately in 80-150 msec. This finding is confirmed independently by
      two original techniques which are advanced by the authors and enable
      identification of such differences in poststimulus patterns. The techniques have
      the advantage that they make it possible to evaluate the differences with the
      given significance level.

PMID- 8755052
TI  - [A model of the structure of the dipole source of the alpha rhythm in the human
      visual cortex].
AB  - The model of the alpha-rhythm was studied which consisted of a set of elementary
      dipoles. The dipoles were fixed normally to the surfaces of a cruciform structure
      which imitated the structure of the visual cortex. The magnitude of dipole
      moments varied according to the sinusoidal low. Thus, the effect was produced of
      the waves leaving the epicenters which in one case were located in the lower
      parts of the cruciform structure and at the ends of the side rays of this
      structure in the other case. The model enabled imitation of all experimentally
      found phenomena of the alpha-wave travelling (fronto-occipital travelling,
      rotatory travelling, diagonal and transverse forms). Additionally, the phenomenon
      was found which enabled simulation of the flat EEG with remaining cortical alpha
      activity. The possible velocity of the alpha-wave propagation in the visual
      cortex was calculated. The model can be applied for testing the hypothesis that
      the alpha-rhythm is a scanning mechanism in the visual cortex.

PMID- 8755053
TI  - [The effect of anterior lesions to the medial forebrain bundle on the motor
      activity evoked by a sensory deficit (sensory drive) in rats].
AB  - The orbito-frontal cortex and postcommissural MFB lesions evoked two major
      effects. The first one consisted in an increased need for light stimulation while
      the second one concerned changes in anxiety level with different results
      depending on the lesion location (cortical ot subcortical). The second effect is
      in agreement with P. Simonov's hypothesis concerning the different configurations
      of the CNS structures. Upon destruction of the orbito-frontal area, the dominant
      role in behaviour regulation is taken over by the "emotional part" of the brain,
      whereas the destruction of the postcommissural MFB (reduction of the amygdalar
      influence on the hypothalamus) creates conditions for functional prevalence of
      the "informational brain".

PMID- 8755054
TI  - [The temporal organization of the interneuronal frontal-motor relations in the
      cat neocortex depending on the level of food motivation].
AB  - The multiunit activity in the frontal and sensorimotor cortex was recorded by the
      bundle of nichromic electrodes in waking cats with different levels of alimentary
      motivation. Interaction between the neighbouring and distant neurons was
      evaluated by means of statistical cross-correlation analysis of spike trains. It
      was shown that the 24-hour food deprivation increased the number of correlations
      between discharges of the neurons both in the local (between the neighbouring
      neurons in the frontal and sensorimotor areas) and distributed networks
      (interarea correlations between the frontal and sensorimotor cortical neurons)
      with delays in the range of 0-100 ms. This increase was most significant in the
      delay range of 0-30 ms.

PMID- 8755055
TI  - [The effect of multiple administrations of GABA and bicuculline into the rat
      neostriatum on the realization of a food-acquisition habit].
AB  - The effects of three-week daily intrastriatal GABA (45 mcg) and bicucullin (5
      mcg) microinjections on operant performance in the Skinner's box were studied in
      rats. GABA was shown to facilitate the operant responses (the rate of lever
      pressings increased, spontaneous motor activity became optimized). Bicucullin
      produced the opposite effects, i.e., the operant skill practically disappeared at
      the second-third week of injections. The operant behaviour was substantially
      influences by such factors as neurosurgery trauma, narcosis, and injections as
      demonstrated in control experiments. The findings suggest the involvement of
      GABAergic neostriatal system in realization of conditioned motor alimentary
      behaviour.

PMID- 8755056
TI  - [An aversive olfactory signal during the Y-maze learning of mice selected for
      greater or lesser brain weight].
AB  - Learning abilities of mice selected by the small and large brain weights were
      studied in Y-maze. Thirsty mice were trained to find water in one of the maze
      arms. The minimal latency of this reaction reached in the process of learning was
      shorter in the mice selected by the heavy brain. Benzaldehyde which is commonly
      supposed to be an aversive olfactory stimulus being presented before drinking
      sharply increased the latency, nevertheless, it remained shorter in mice with
      heavy brain. The response to the aversive stimulus varied between the
      individuals, especially in mice selected by the small brain weight.

PMID- 8755057
TI  - [The effect of blockade of the AMPA/kainate receptors of the nucleus accumbens on
      synaptic dopamine release during an emotional conditioned response].
AB  - In vivo microdialysis combined with HPLC-EC analysis was used to monitor
      extracellular dopamine in the medial nucleus accumbens of rats. A conditioned
      emotional response to a contextual cue was accompanied by a prolonged release of
      dopamine in the nucleus accumbens. AMPA/kainate antagonist CNQX (100 mcM, intra
      accumbens) had no effect on the conditioned dopamine release during the
      conditioned emotional responses. The data indicate that AMPA/kainate receptors of
      the nucleus accumbens are not involved in the regulation of the conditioned
      dopamine release.

PMID- 8755058
TI  - [Hypothalamic neurons and zoosocial interactions].
AB  - Unit activity in the lateral hypothalamic area was recorded in rats after testing
      by the emotional resonance technique. The rats were divided in two groups by
      their reaction to the suffering cry of the partner ("victim"). Rats from the
      group I ("altruists") escaped ("victim") crying, and those from the group II
      ("egoists") did not. Activity of neurons was analysed in hungry rats, after
      feeding, after placing the "victim" into the experimental chamber, during
      intracranial emotionally positive and negative stimulation, and during crying of
      the "victim". The results showed that the majority of neurons of the rats from
      the I group responded to the partner's crying in the same way as to the
      intracranial emotionally negative stimulation and the reaction of the neurons of
      the rats from the II group was either poorly expressed or resembled that to the
      intracranial emotionally positive stimulation.

PMID- 8755059
TI  - [The effect of serotonin on the cross-correlation of neuronal activity in
      surviving cortical slices].
AB  - Serotonin-induced changes in crosscorrelation functions of the trains of neuronal
      activity were studied in surviving slices of the guinea pig cerebral cortex.
      After serotonin administration into the incubation medium and its washing-out the
      value of the crosscorrelation function in the zero bin increased as compared with
      its initial value if the background impulsation rate of both neurons was high and
      decreased if the background rate was low. This finding substantiates the earlier
      advanced hypothesis that serotoninergic system is related to the positive
      reinforcement in learning and influences the efficiency of the cortico-cortical
      synapses increasing it when the initial excitation of the presynaptic neuron is
      high and decreasing when the background presynaptic excitation level is low.

PMID- 8755060
TI  - [Catecholamine levels and tyrosine hydroxylase activity in the brain structures
      of male mice with a determined behavioral type in a population].
AB  - Biosynthetic activity in brain catecholaminergic neurons was studied in male mice
      with genetically determined dominant (PT strain) and subordinate (CBA) behaviour.
      The dominant PT mice were characterized by higher levels of catecholamines and
      tyrosine hydroxylase activity in most of the brain regions in comparison with
      subordinate CBA mice. Percent of animals with dominant type of behaviour was high
      among the hybrid F1 males derived from PT and CBA mice. These offsprings
      inherited also the high levels of noradrenaline and dopamine as well as the high
      tyrosine hydroxylase activity in the striatum and the brain stem. The obtained
      data suggest that the level of biosynthetic activity in the brain
      catecholaminergic neurons is essential for coordination of the brain
      neurochemical systems in expression of the dominant male mice behaviour in a
      population.

PMID- 8755061
TI  - [The effect of stress in pregnant rats on the anxiety level in their offspring].
AB  - The anxiety level was studied in offsprings of dams stressed during pregnancy.
      Increased number of resorptions and stillbirths was mentioned. The experimental
      pups (1 month old) had lower locomotion and higher anxiety levels as compared to
      the control animals. There were no differences in anxiety and locomotion levels
      in males (4 months old) between the experimental and control groups. In
      experimental females of this age anxiety was decreased and locomotion increased.
      Aggressive behavior was more expressed in the experimental animals of both sexes.

PMID- 8755062
TI  - [The prophylactic effect of negatively charged air ions in acute stress in rats
      with different typological behavioral characteristics].
AB  - Typological characteristics of behaviour of 63 male white rats weighing 200-250 g
      were estimated by their locomotion in the open field. Acute stress was induced by
      putting the rats into narrow tubes for 1 h. Prior to the experiment, the rats
      were exposed to the air ions produced by Chizhevskii air ionizer ("Elion-132")
      for 2 h daily within a week. It was found out that the expression of separate
      pathological stress-induced changes depended on typological characteristics of
      rats. The air ions were shown to prevent completely the development of
      physiological changes caused by acute immobilization, including arterial pressure
      increase, gastric mucosa injuries (erosions, haemorrhage), changes in respiratory
      enzyme activity (succinate dehydrogenase and NADH-dehydrogenase) in brain cells,
      cardiac and adrenal mass increase in rats with the active type behaviour.

PMID- 8755063
TI  - [The consolidation and reproduction of a state of haloperidol-induced catalepsy].
AB  - Catalepsy induced by a single intraperitoneal injection of haloperidol (2.5
      mg/kg) was consolidated and without additional influences and retained within 2
      week (being tested on the 2nd, 7th, and 14th days after injection). Enhancement
      of catalepsy retrieval was observed during testing of the same animals on the
      14th day as compared with the 7th day. Maximal catalepsy expression was reached
      after 2 hours of testing procedure which points to the existence of the mechanism
      of autoenhancement of retrieval which is probably underlain by the automodulation
      of the long-lasting modulatory DA receptors. The retrieval of catalepsy is
      suggested to be induced by a situational conditioned stimulus, since on the 2nd,
      7th and 14th days it may be reproduced without repeated haloperidol injection
      only in the testing box.

PMID- 8755064
TI  - [The distribution of serotonin 5-HT1A receptors in the brain of rats genetically
      predisposed to the development of catalepsy].
AB  - [3H]-8-OH-DPAT specific binding was determined in brain regions of S40 rats
      selected for predisposition to freezing (catalepsy). Significant decrease in Bmax
      in the frontal cortex and increase in Kd in the hippocampus as well as a strong
      tendency to a decrease in Bmax in the midbrain and hypothalamus were shown in
      cataleptic rats. The findings suggest the involvement of serotonin 5-HT1A
      receptors in the genetic predisposition to fear-induced passive defensive
      response.

PMID- 8755065
TI  - [Local destruction of Deiters' lateral vestibular nucleus (an experimental model
      of a focal brain stem lesion)].
AB  - The experimental rat model of the local brainstem destruction by isolated
      electrical coagulation of the lateral vestibular nucleus Deiters was offered for
      studying the adaptive-compensatory CNS reactions after acute brainstem lesions.
      Morphological changes and functional derangements were correlated in 22 animals.
      Neurological disorders and behavioural reactions were reproducible and stable in
      rats with exact localization of coagulated foci. The results demonstrate the
      adequacy of the proposed model.

PMID- 8755066
TI  - [A model of audiogenic epilepsy--rats of the Krushinskii-Molodkina strain. Proof
      of genetic homogeneity].
AB  - Genetical homogeneity of Krushinskii-Molodkina (KM) stock was studied by the
      method of reciprocal transplantation of skin. The rats were selected inside
      genealogic card from 5 different substrains of the 20th generation of brother
      sister crossing (F 20). The tail-to-tail transplantation was made by the scheme
      of double reciprocal ring in 9 females from the KM stock. Observations within 314
      days showed a good condition of the transplants. The obtained data suggest that
      Krushinskii-Molodkina rats are an inbred strain.

PMID- 8755067
TI  - [Off and on stimulation exerts a contrary action on the functional status of the
      human brain].

PMID- 8755068
TI  - [The cross-correlational coefficients of cortical biopotentials and the autonomic
      indices during the mental reproduction of emotional states in man].

PMID- 8755069
TI  - [The effect of dopamine and noradrenaline antibodies on pain sensitivity in
      animals].

PMID- 8755070
TI  - [The effect of the stage of the estrous cycle and of acute stress on sugar
      consumption by female white rats].

PMID- 8755072
TI  - [Changes in the electrical characteristics of the command neurons during the
      acquisition of a conditioned defensive reflex in the snail].

PMID- 8755071
TI  - [Sex-dependent differences in the action of chronically administered beta
      casomorphin-7 on the behavior of white rat pups].

PMID- 8755073
TI  - [The information-energy concept of the origin of the psyche].
AB  - An attempt is made to understand the origin of psyche on the basis of natural
      sciences as a result of biological evolution. Organization and control of the
      artificial systems is based on purely informational, or formal interaction, while
      in the living organisms the basis is informational-energetic, or conceptual
      interaction. This type of interaction is the basis of self-organization of the
      living systems at all levels. It is suggested that the principle of self
      organization is crucial for emergence of mind.

PMID- 8755074
TI  - Venous recanalization by metallic stents after failure of balloon angioplasty or
      surgery: four-year experience.
AB  - PURPOSE: This retrospective study describes our updated experience in treating
      venous stenoses and occlusions with metallic endovascular stents. METHODS:
      Gianturco, Palmaz, and Wallstent stents were placed in 55 patients over a 4-year
      period. Stent sites included the subclavian veins (9), innominate veins (3),
      superior vena cava (4), inferior vena cava (3), iliac veins (29), femoral veins
      (5), and portal veins (6). The most common indications for stent placement were
      malignant stenoses and chronic pelvic venous occlusions. Venoplasty and/or
      urokinase were used as ancillary therapy. Patients were anticoagulated for 3-6
      months. Follow-up included clinical assessment and duplex ultrasound. RESULTS:
      Lifetable analysis shows 59%, 63%, and 72% primary, primary assisted, and
      secondary 1-year patency rates, respectively. The 4-year primary patency rates
      were the same. Duration of patency depended on the venous site. Death was a
      complication of stent placement in 2 patients and 12 patients died within 6
      months after stent placement from primary disease progression. Although early
      failures were more common in stents placed across occlusions than stenoses, 1
      year secondary patency rates were comparable. Primary patency rates were only
      slightly lower in patients with malignant obstruction than in patients with
      benign disease. CONCLUSION: Endovascular stent placement provides a nonsurgical
      alternative for reestablishment of venous flow and symptomatic relief in patients
      with benign as well as malignant venous obstruction.

PMID- 8755075
TI  - Ankle-arm index, angiography, and duplex ultrasonography after recanalization of
      occlusions in femoropopliteal arteries: comparison of long-term results.
AB  - PURPOSE: Comparison of the relative values of the ankle-arm index (AAI) at rest
      and after exercise, angiography, and duplex ultrasonography for the follow-up of
      percutaneous transluminal angioplasty (PTA) in patients with peripheral vascular
      disease. METHODS: Thirty-two patients were prospectively followed after
      technically and clinically successful PTA of a femoropopliteal occlusion. The
      patency of the femoropopliteal artery was assessed for 1 year using AAI
      measurements at rest and after exercise; duplex ultrasonography at 4, 12, 24, 36,
      and 52 weeks; and angiography at 3 and 12 months after PTA. RESULTS: Patency was
      highly dependent on the measurement technique. The cumulative patency after 1
      year determined with the AAI at rest and during exercise, by angiography, and by
      duplex ultrasonography was 74%, 19%, 31%, and 32%, respectively. Seventy-five
      percent of the restenoses occurred at the site of the treated occlusion.
      CONCLUSION: Duplex ultrasonography is most suitable for this assessment, as it
      causes no patient discomfort and the specificity is better than AAI after
      exercise because vascular disease in other, proximal segments does not interfere
      with the results.

PMID- 8755076
TI  - Diagnosis of an accessory portal vein and its clinical implications for
      portosystemic shunts.
AB  - PURPOSE: To present a peculiar anatomic portal veins variant and evaluate its
      clinical implications. METHODS: Among 118 consecutive patients undergoing
      transjugular intrahepatic portosystemic shunting (TIPS), six male patients were
      found to have an accessory portal vein, which was seen during direct
      portography.R ESULTS: In all six patients, portograms showed an accessory small
      caliber vein parallel to the trunk of the main portal vein ending in the right
      lobe of the liver. Two of the six accessory portal veins drained blood from
      coronary veins, precluding access to coronary vein embolization during TIPS.
      CONCLUSION: An accessory portal vein is a rare anatomical variation with clinical
      significance for both surgical shunt placement and TIPS, as well as for
      transportal embolization of coronary veins.

PMID- 8755077
TI  - The radiological management of biliary complications following liver
      transplantation.
AB  - PURPOSE: Biliary complications contribute significantly to morbidity and
      mortality in the liver transplant recipient. Surgery has been the mainstay of
      therapy, but interventional radiological techniques have made significant
      progress. METHODS: Diagnostic percutaneous transhepatic cholangiography (PTC) was
      performed in 12 patients; percutaneous transhepatic drainage (PTD) was performed
      in 10 patients. Additional interventional procedures included laser lithotripsy,
      biopsy, dilatation, and stent implantation. RESULTS: In 6 patients PTC revealed
      anastomotic, and in 6 patients nonanastomotic biliary strictures. Four patients
      had intrahepatic stones. Biliary strictures were treated by implantation of
      Palmaz stents in 5 of 6 patients with anastomotic strictures, and in 3 of 6
      patients with nonanastomotic strictures. The intrahepatic stones were fragmented
      with dye laser lithotripsy under cholangioscopic control in 3 of 4 patients. One
      spontaneous stent migration after 24 months and one stent occlusion were
      observed; the remaining stents are still patent. Patients with anastomotic
      strictures had a more favorable outcome: 5 of 6 of these patients are still alive
      and symptom-free after an average of 27.4 months, but only 3 of 6 patients with
      nonanastomotic strictures are alive after an average of 9.8 months. CONCLUSION:
      The different outcomes in patients with anastomotic versus nonanastomotic
      strictures may be explained by the different causes of these types of stricture.

PMID- 8755079
TI  - Recanalization of aged venous thrombotic occlusions with the aid of a rheolytic
      system: an experimental study.
AB  - PURPOSE: The suitability of a rheolytic system for recanalization of aged venous
      thrombotic occlusions was tested in an animal experiment. METHODS: The system
      consists of a flush-suction catheter and a high-pressure liquid pump. Thrombosis
      was experimentally induced in 13 venous segments of 10 adult goats. RESULTS:
      After a mean period of 12 days, a complete thrombectomy using the flush-suction
      system was achieved in 12 cases. No complications such as perforation or
      dissection were observed. CONCLUSION: This system seems to be an appropriate
      device for percutaneous transluminal venous thrombectomy, even in older
      occlusions.

PMID- 8755078
TI  - Neointimal hyperplasia in low-profile Nitinol stents, Palmaz stents, and
      Wallstents: a comparative experimental study.
AB  - PURPOSE: To compare neointima formation following insertion of low-profile
      Nitinol stents, Palmaz stents, and Wallstents. METHODS: Nitinol stents, Palmaz
      stents, and Wallstents similar in size were transfemorally inserted into the
      iliac arteries of 12 sheep. Four stents per sheep were deployed; the position of
      the stents was varied so that each type of stent was placed in each position
      (right or left, proximal or distal) with equal frequency. Stent patency was
      followed by angiography. Six sheep were euthanized after 1 month, and the
      remaining six after 6 months. Iliac arteries were removed en bloc and prepared
      for histological examination. Neointimal and medial thickness were measured by
      light microscopy, and measurements were analyzed statistically. RESULTS: Mean
      neointimal thickness both over (NO) and between (NB) the stent struts was greater
      in Wallstents (NO = 0.341 mm, NB = 0.368 mm) than in the Nitinol (NO = 0.260 mm,
      NB = 0.220 mm) and Palmaz stents (NO = 0.199 mm, NB = 0. 204 mm), but differences
      were not significant (p > 0.05). Medial atrophy in the area between the stent
      struts was greater in Wallstents compared with Nitinol and Palmaz stents (p <
      0.007 and p < 0.02, respectively); in the area under the stent struts there was a
      significant difference only between Palmaz stents and Wallstents (p < 0.02).
      CONCLUSION: Under defined experimental conditions, none of the three types of
      stent appears to be preferable to the others regarding neointima formation in the
      short- to mid-term follow-up period.

PMID- 8755080
TI  - Experimental impeller fragmentation of iliocaval thrombosis under tulip filter
      protection: preliminary results.
AB  - PURPOSE: To assess the efficacy of catheter fragmentation of massive caval
      thrombosis and of filter protection against procedure-related pulmonary embolism.
      METHODS: In 10 sheep, a self-expanding tulip-shaped filter made from Wallstent
      mesh (diameter 25 mm) was introduced from the right jugular approach into the
      proximal inferior vena cava. Experimentally induced massive iliocaval thrombosis
      was fragmented by an impeller catheter (expanded diameter 14 mm), which was
      advanced coaxially through the sheath of the expanded filter. Post-procedural
      cavography and pulmonary angiography were performed to document the extent of
      caval recanalization and pulmonary embolism. RESULTS: In all cases, impeller
      fragmentation cleared the inferior vena cava and the iliac veins of thrombi
      completely. Fragments washed downstream were trapped in the filter. In two of the
      first cases, parts of the clots caused pulmonary embolism before the filter was
      in place. Further events were avoided by a modification of the experimental
      setup. Except for some small peripheral perfusion defects in two cases, pulmonary
      angiograms did not show any incidence of pulmonary embolism. CONCLUSION: Our
      preliminary results suggest that impeller fragmentation of iliocaval thrombi
      under tulip filter protection is effective and does not cause significant
      pulmonary embolism.

PMID- 8755081
TI  - Use of sonicated albumin (Infoson) to enhance arterial spectral and color Doppler
      imaging.
AB  - PURPOSE: To examine the effect of an ultrasound contrast medium (UCM), Infoson,
      on Doppler examination of stenotic arteries. METHODS: Stenoses were created in
      the common carotid artery of six piglets, and examined with spectral Doppler and
      color Doppler imaging during UCM infusion in the left ventricle. RESULTS: UCM
      caused a mean increase in recorded maximal systolic and end-diastolic velocities
      of 5% and 6%, respectively, while blood flow remained constant. Increased
      spectral intensity with UCM was accompanied by spectral broadening. Reduction of
      spectral intensity by adjustment of Doppler gain counteracted the velocity
      effects and the spectral broadening. With color Doppler, UCM caused dose
      dependent color artifacts outside the artery. Flow in narrow stenoses could be
      visualized with UCM. CONCLUSION: The effects of UCM on velocity measurements were
      slight, and were related to changes in spectral intensity. With color Doppler,
      UCM may facilitate flow detection, but color artifacts may interfere.

PMID- 8755082
TI  - Traumatic fistula between the left anterior descending coronary artery and a left
      ventricular pseudoaneurysm.
AB  - A 44-year-old man presented with a fistula of the left anterior descending (LAD)
      coronary artery to a left ventricular pseudoaneurysm 6 months after a stab injury
      in the left anterior chest. The color Doppler echocardiography suggested, and
      angiography confirmed, the diagnosis and the lesion was treated successfully.
      Traumatic coronary artery fistulas are rare complications, and color Doppler
      echocardiography proved useful for the diagnosis.

PMID- 8755083
TI  - Entanglement of a pigtail catheter by the chordae tendineae of the tricuspid
      valve during pulmonary angiography.
AB  - Two cases are presented in which a pigtail catheter was entrapped by the chordae
      tendineae of the tricuspid valve during pulmonary arteriography. A technique for
      removal of the catheter from its entanglement by the chordae tendineae is
      described. Caution must be taken when advancing through the right ventricle a
      catheter that appears to be entrapped by the chordae tendineae. When such an
      entanglement occurs, measures to reduce the risk of rupturing a papillary muscle
      must be taken.

PMID- 8755084
TI  - Posttraumatic high-flow priapism treated by N-butyl-cyanoacrylate embolization.
AB  - A patient with high-flow priapism was treated by transcatheter embolization of a
      posttraumatic left cavernosal arteriovenous fistula using N-butyl-cyanoacrylate
      (NBCA), resulting in complete detumescence. Erectile function has been preserved
      during a 3-month follow-up. Only two patients with NBCA embolization for high
      flow priapism have been reported previously.

PMID- 8755085
TI  - Selective embolization of bilateral arterial cavernous fistulas for posttraumatic
      penile arterial priapism.
AB  - A 22-year-old man suffered a hiking accident with perineal trauma and developed a
      nonpainful priapism secondary to bilateral arterial-cavernosal fistulas. To
      minimize the risk of impotence in this young patient, successive selective
      embolizations with autologous blood clot were performed to close the fistulas.
      This led to an uncomplicated full recovery. No fistula was detectable on Doppler
      ultrasonography at 1-year follow-up. Review of the literature confirms the safety
      of embolization with autologous clot.

PMID- 8755086
TI  - Systemic supply to a pulmonary arteriovenous malformation: potential explanation
      for recurrence.
AB  - A pregnant woman presented with hereditary hemorrhagic telangiectasia (Osler
      Weber-Rendu syndrome) and a single pulmonary arteriovenous malformation (AVM)
      that had been embolized 5 years previously. Partly due to pregnancy,
      recanalization of the aneurysm occurred with subsequent hemoptysis. Despite
      successful therapeutic reembolization of the afferent pulmonary artery,
      hemoptysis recurred 5 days later. At this time, recanalization of the pulmonary
      artery was not demonstrated by pulmonary angiography, but a systemic angiogram
      revealed a bronchial arterial supply to the pulmonary AVM. A systemic supply
      should always be sought in cases of recurrent hemoptysis after technically
      successful embolization of the feeding pulmonary artery.

PMID- 8755087
TI  - Gastric wall dissection as a complication of percutaneous gastrostomy.
AB  - A percutaneous gastrostomy (PG) was complicated by gastric wall dissection and
      partial tube malposition. It occurred after tangential puncture along the greater
      curvature of the stomach which was performed in order to avoid an enlarged left
      lobe of the liver. To prevent this complication we recommend not using
      hydrophilic guidewires during PG.

PMID- 8755088
TI  - Ruptured suprarenal artery aneurysm: angiographic diagnosis and treatment by
      selective embolization.
AB  - The case of a 78-year-old man with retroperitoneal hemorrhage due to a ruptured
      right inferior suprarenal artery aneurysm is presented. The diagnosis was made by
      angiography which allowed immediate embolization of the neck of the aneurysm,
      controlling hemorrhage and obviating the need for surgery. The patient made a
      full recovery with no evidence of further hemorrhage.

PMID- 8755089
TI  - Rheolytic thrombectomy of an acutely thrombosed transjugular intrahepatic
      portosystemic stent shunt.
AB  - As an alternative to chemical thrombolysis, an acutely occluded transjugular
      intrahepatic portosystemic stent shunt in a 72-year-old woman was successfully
      recanalized using a 5 Fr rheolytic catheter system. No adjunctive thrombectomy
      treatment was necessary. The underlying stenotic leason was treated with
      percutaneous transluminal angioplasty and a Palmaz stent. Immediately after the
      intervention optimal shunt flow was achieved. Ascites vanished within a few days
      and no further bleeding complications appeared.

PMID- 8755090
TI  - In situ formation of a loop snare for retrieval of a foreign body without a free
      end.
AB  - A technique is described that allowed percutaneous retrieval of an endoscopically
      placed, obstructed biliary stent using loop snare capture of an angled
      hydrophilic wire which was wrapped around the stent initially.

PMID- 8755092
TI  - Re: complication of pulmonary arteriography: contrast extravasation from a wedged
      pigtail-shaped catheter.

PMID- 8755091
TI  - Stent-graft in the management of superior vena cava syndrome.
AB  - We report the use of a Dacron-covered Gianturco-Rosch Z (GRZ)-stent to treat
      malignant obstruction of the superior vena cava (SVC). Initial treatment with an
      uncovered GRZ-stent was suboptimal due to protrusion of tumor-thrombus through
      the stent struts into the SVC lumen. Placement of a coaxial Dacron-covered stent
      graft relieved the residual obstruction due to tumor within the SVC.

PMID- 8755094
TI  - Chemical structure of descriptors with an active hydrogen atom in certain
      bioregulators.
AB  - The chemical structure of descriptors (D) for some plant growth regulators (PGR),
      herbicides, pesticides and drugs is described. The presence of an active hydrogen
      atom in molecules is an essential factor determining biological activity of
      chemicals. The results obtained from the study of dependence existing between the
      structure of a certain substance and its biological activity may be used in
      designing of novel compounds which possess in biological activity.

PMID- 8755096
TI  - [Taurine induces an imbalance in the pool of neuroactive amino acids and biogenic
      amines in regions of the brain].
AB  - The paper deals with the consequences of exogenous taurine (Tau) administration
      (650 mg/kg, i.p., singly, for 30 min) and possible mechanisms of this compound
      participation in the formation of the structure of the neuroactive amino acid
      pool, biogenic amines and their metabolites in the hypothalamus (H), basal
      ganglia (BG) and cerebellum (C) of the brain of male rats weighing 160-280 g. The
      concentrations of amino acids as OPA derivatives were determined by reverse-phase
      HPLC and the content of biogenic amines and their metabolites--by ion-pair HPLC
      ECD. The Tau load was followed by an elevation of the concentrations of
      glutamate, aspartate and their amides, GABA and tyrosine concentrations in
      cerebellum whereas in basal ganglia that of tyrosine and dopamine. The
      tryptophan, beta-alanine, dioxyphenylacetic acid, dopamine and norepinephrine
      levels were diminished in hypothalamus. The metabolic and functional
      relationships governing the imbalance of the neuroactive amino acid and biogenic
      amine pool in the neuroactive amino acid and biogenic amine pool in the CNS
      occurring after the Tau administration in vivo are interpreted using statistical
      analysis.

PMID- 8755095
TI  - [Methods for determining the activity of factors VII, VIII, IX and X of the blood
      coagulation system].
AB  - The existing methods for determination of activity of the VII, VIII, IX and X
      factors of the coagulation system have been analyzed. The comparative evaluation
      of their efficiency which depends on complexity, reprocibility, sensibility and
      test performance time is considered. The important role of these methods in
      scientific investigation for the diagnosis of haemophilia A, haemophilia D,
      factors VII and X deficiency for the purposes of therapy is emphasized.

PMID- 8755097
TI  - [Enzyme biosensors for penicillin determination based on conductometric planar
      electrodes and pH-sensitive field effect transistor].
AB  - The enzyme biosensors for penicillin determination based on conductometric planar
      electrodes and pH-sensitive field effect transistors have been described and
      their working parameters have been compared. The influence of pH, buffer capacity
      and ionic strength of the samples on the biosensors response has been studied.
      Short response time and high operational stability are characteristics of the
      developed biosensors.

PMID- 8755098
TI  - [Activity of Na+, K+-ATP-ase isoenzymes in the cerebral cortex and their
      sensitivity to sodium dodecyl sulfate in rat postnatal ontogenesis].
AB  - The comparative study of activities of Na+, K(+)-ATPase alpha (+)- and alpha
      isozymes in rat brain cortex in the postnatal period is conducted. It is shown,
      that the rates of isozymes expression are not different and levels of their
      activities reach maximum to the 30th day after birth. Na(+), K(+)-ATPase
      resistance to SDS inactivation increases with the age, that reflects possible
      changes in the peculiarities in structural organization of isozymes protein-lipid
      complex. Results are discussed from the view point of the adaptive changes in the
      process of structural-metabolic organization of biomembrane function occurring in
      ontogenesis.

PMID- 8755099
TI  - [Activity of Krebs cycle enzymes in Staphylococci containing determinants of
      antibiotic resistance].
AB  - The activity of enzymes, which catalyse reaction of the Krebs cycle and some
      biosynthetic reactions, connected with the cycle, has been comparatively
      analyzed. A decrease in the intensity of basic reactions of tricarboxylic acid
      cycle has been defined. Considerable increase of anaplerotic processes and amino
      acid synthesis in plasmid-containing variants of staphylococci is shown.

PMID- 8755100
TI  - [Activity of key enzymes of the glycolytic and pentose phosphate pathways in
      plasmid-containing Staphylococci].
AB  - Comparative data concerning enzyme activities of central metabolic pathways in
      pathogenic staphylococcus strains, containing and not containing plasmids of
      resistance to different antibiotics has been presented. An increase in the
      activity of key enzymes of glycolytic pathway: 6-phosphofructokinase, fructose
      1,6-biophosphate aldolase, lactate dehydrogenase, and a decrease in the activity
      of enzymes of the pentose phosphate cycle: glucose-6-phosphate dehydrogenase in
      antibiotic resistant strains, were defined.

PMID- 8755101
TI  - [Role of phospholipids in functionally different cell membranes under conditions
      of antioxidant system disturbance].
AB  - Vitamin E deficiency in organism leads to microsome membrane phospholipid
      composition changes, oxidation, superoxide dismutase (SOD) activity decrease,
      accompanied with the disorders of lung and liver tissues functional state which
      is connected with regulation of membrane penetration. The negative effect of E
      hypovitaminosis more affects the liver than lung, which is caused by their
      different functional purposes, peculiarities of metabolic processes as well as by
      the content of biomembrane structural components. Vitamin E protects
      phospholipids from oxidation, regulates AOS condition, SOD-activity and promotes
      in such way the tissue functional disturbances correction of the animals tested.
      New preparation "Calmophyl" is a phospholipid complex from marine organisms with
      surfactant-kind effect, which displays antioxidative properties and decreases
      toxic affect of CCl4, corrects functional tissue disorders, regenerates normal
      activity of enzymes. Preparation of natural phospholipids has been shown to be
      capable to stabilize cell membranes probably by means of replacing the membrane
      phospholipid composition and decreasing disturbances in the antioxidative system.

PMID- 8755102
TI  - [Study of the interaction of ribonuclease with liposomes using competitive
      analysis].
AB  - Competitive interaction of fluorescent probe DSM and ribonuclease with liposomes
      composed of phosphatidylcholine and diphosphatidylglycerol mixtures has been
      investigated. Parameters of probe and protein binding to lipid bilayer have been
      estimated.

PMID- 8755103
TI  - [Thiol group content in blood serum and in tumor tissue of rats with intact and
      radioresistant variants of Guerin carcinoma].
AB  - Interrelation between the formation of the secondary acquired radioresistance of
      Guerin carcinoma cells and dynamics of content of thiol groups in the tumour
      tissue and blood serum of rats have been studies. It is established that the
      tumour tissue and normal tissues (blood serum) of rats with Guerin's carcinoma
      respond to the fractional radiation action and to repeated courses of radiation
      therapy by the reactive increase of the number of free non-protein thiol groups
      and by the decrease of the content of protein thiols. The use of local superhigh
      frequency-hypothermia in the pattern of treatment of the Guerin carcinoma strain
      resistant to irradiation is accompanied by the increase of the reaction capacity
      of non-protein thiol groups of the tumour tissue. At the same time the level of
      general thiol groups in the blood serum decreases while their reactivity
      increases.

PMID- 8755104
TI  - [Features of vitamin D3 metabolism in liver cells in experimental diabetes
      mellitus].
AB  - The uptake of vitamin D3 by the liver cells and its hydroxylation in the
      hepatocytes of rats at experimental diabetes has been studied. It is proved that
      in this pathology the disturbances of vitamin D3 exchange in the rat liver take
      place. It is concluded that the lowering of the level of absorption of vitamin D3
      by hepatocytes and its transportation to these cells from reticulocytes as well
      as the inhibition of vitamin D3-25-hydroxylase liver systems can be the most
      probable cause of these disturbances.

PMID- 8755105
TI  - [Status of the antioxidant, monooxygenase and humoral immune system of the body
      in d-galactosamine hepatitis].
AB  - Galactosamine model of toxic hepatitis in rats which, as to its morphobiochemical
      picture, is considered adequate to human hepatitis was used to study the role of
      disturbances of the functional state of antioxidant and monooxygenase systems as
      well as humoral area of the systems of immune protection in pathogenesis of the
      given disease. It is shown that most components of enzymatic and nonenzymatic
      antioxidant system (superoxide dismutase, catalase, glutathione peroxidase,
      restored glutathione, phospholipids) are considerably inhibited by the toxin
      effect. At the same time content of ceruloplasmin is increased in the blood
      plasma. Considerable disturbances are also observed in the humoral chain of the
      immune system (content of immunoglobulins and circulating immune complexes
      varies) and in the processes of microsomal oxidation.

PMID- 8755106
TI  - [Comparative study of the immunogenicity of various forms of Naja oxiana
      cardiotoxin].
AB  - Comparative study of the immune sera from rabbits immunized with both formol and
      native cardiotoxins, cardiotoxin incorporated into sphingomyelin
      phosphatidylcholine-cholesterol liposome stabilized with osmium tetroxide, and a
      cardiotoxin-succinylated bovine albumin conjugate was performed. The latter
      produced antibodies identified by immunodiffusion assay. The highest survival was
      observed in animals treated with antiserum to cardiotoxin-albumin conjugate,
      followed by antitoxin to combination of formol and native cardiotoxins. Antiserum
      to cardiotoxin in liposome was ineffective.

PMID- 8755107
TI  - [Optimization of a method of production of allergen extracts from ambrosia
      pollen].
AB  - Peculiarities of allergens extraction from the intact and destructed pollen
      grains of Ambrosia artemisiifolia L. have been studied, and the effect of the
      content of extracting buffer on stability of the obtained allergen extracts has
      been investigated. It is established that mechanical destruction of pollen during
      extraction permits decreasing protein output, increasing specific activity of the
      extracts and accelerating the procedure of their production. Introduction of some
      protective additions to the composition of the extracting buffer permits
      essentially increasing stability of the extracts under long-term storage at 4
      degrees C.

PMID- 8755108
TI  - [Use of parameters of E-rosette formation and electrophoretic mobility for
      comprehensive evaluation of the functional state of leukocytes].
AB  - The influence of some drugs on E-rosette formation by lymphocytes and on
      electrophoretic mobility of neutrophilic leukocytes has been studied. It has been
      found, that the character of drugs influence coincides with common directivity of
      their action on two main cell signalling systems: adenylate cyclase and
      polyphosphoinositide. The possibility of use of the parameters studied for the
      complex evaluation of functional state of leukocytes is discussed.

PMID- 8755109
TI  - [Protein and RNA synthesis in larvae of the yellow mealworm beetle (Tenebrio
      molitor) during cooling and cold acclimatization].
AB  - Functioning of protein-synthesis system freeze-avoiding larvae of Tenebrio
      molitor. (Tenebrinidae family) has been investigated at temperature lowering to 6
      8 degrees. It has been shown that mealworms maintain the protein and RNA
      biosynthesis under cold acclimation (6-8 degrees C). Judging by the angle of
      inclination of Arrenius of plot reorganization of protein synthesis system takes
      place in the temperature range 0-10 degrees C. Biosynthesis of proteins at the
      room and low temperatures is inhibited by cycloheximide while biosynthesis of RNA
      -by alpha-amanitine.

PMID- 8755110
TI  - [Structural-functional changes in erythrocyte membranes in bovine
      lympholeukemia].
AB  - The condition of lipid peroxidation and activity of enzymes of protective
      glutathione-dependent anti-oxidation system of erythrocytes: glutathione
      peroxidase (GSH-P) and glutathione reductase (GSH-R) in cows with leukosis has
      been studied. The decrease of the level of MDA and GSH-R activity was accompanied
      by GSH-P activation depending on the stage disease. The considerable lowering of
      Ca2+ transport to erythrocytes was shown on hematological stage of leucosis. The
      qualitative composition of membrane proteins does not change according to gel
      electrophoresis data. But the quantity of main cytoskeleton protein, spectrin,
      increases in the "white shadows" of erythrocytes in the animals with leucosis.

PMID- 8755111
TI  - [Free radical processes in the rat blood during hyperbaric oxygenation and in the
      posthyperoxic period].
AB  - Effects of prolonged action of low-pressure oxygen (0.3 MPa, 5h) on the free
      radical oxidation (FRO) intensity were investigated just after oxygen exposure
      and 1, 3, 7, days after that. The FRO increase against the background of the anti
      radical systems depression was shown by means of blood plasma chemiluminescent
      analysis. Under these conditions SOD activity and the content of diene conjugates
      and Schiff's bases increase in erythrocyte membranes. The displacement of
      equilibrium between pro- and antioxidants and antioxidants contents towards the
      latter took place in blood plasma on the 1st day after oxygen exposure. The
      erythrocyte SOD activity was raised while catalase activity was diminished. The
      last one was accompanied with the decrease in erythrocyte membrane diene
      conjugates amount. The secondary blood plasma and erythrocyte membrane FRO
      elevation was observed on the 3rd day after the exposure and, it was held on the
      7th day after hyperoxia. The FRO increase in post-hyperoxia period was
      established.

PMID- 8755113
TI  - [Effect of sodium nitrate on oxidative phosphorylation in liver mitochondria of
      newborn and adult rats].
AB  - Oxidative phosphorylation in the liver mitochondria of new-born and adult rats
      has been studied as affected by nitrates. It was established that the conjugation
      between the processes of respiration and phosphorylation is disturbed, energy
      efficiency of respiration in the liver mitochondria decreases in the new-born and
      adult animals. The found disturbances are more distinct in the new-borns that is
      evidenced by the dose-dependent effect under nitrate intoxications established in
      this group of animals.

PMID- 8755112
TI  - [Antiradical and antioxidant activity of derivatives of 1,2,4-triazole and
      quinazoline in cerebral ischemia].
AB  - Antioxidant and antiradical activity of 1,2,4-triazole and quinazoline
      derivatives inhibiting superradical at the initial stages of free-radical
      oxidation have been studied in vitro by the method of Hara P, Mista, 1972. It is
      acceptable for the determination of antiradical and antioxidant activity of newly
      synthesized compounds.

PMID- 8755114
TI  - Presynaptic GABAA receptors in vertebrate synapses.
AB  - The presynaptic gamma-aminobutyric acidA (GABAA) receptor has long been
      considered as the site for 'presynaptic inhibition' of synaptic transmission in
      the central nervous system (CNS). However, recent reports have indicated that the
      activation of GABAA receptors depolarizes primary afferent neurons and actually
      facilitates the release of GABAA, noradrenaline, adenosine, and luteinizing
      hormone (LH) in central and peripheral tissues. Isoguvacine, a GABAA receptor
      agonist, enhances substance P (SP) release in the spinal cord. GABAB receptor
      agonists, bu not GABAA receptor agonists, produce behavioral antinociception in
      the spinal cord. Baclofen does not directly depolarize the postsynaptic membrane,
      but presynaptically inhibits the activity of dorsal horn neurons. The excitatory
      postsynaptic potential (EPSP) evoked by stimulation of dorsal root C-fibers is
      inhibited by baclofen. Baclofen and GABA inhibit SP release from the primary
      afferent terminals by activating GABAB receptors. The activation of GABAB
      receptors inhibits calcium currents in neurons of dorsal roots ganglia (DRG). It
      is likely that the GABAA receptors act as a site for 'presynaptic facilitation'
      of transmitter release in the CNS.

PMID- 8755115
TI  - Remnant-stump early gastric cancer following partial gastrectomy.
AB  - Eight rare cases of remnant-stump early gastric cancer (RS-EGC) were
      investigated, retrospectively. The incidence of RS-EGC was 0.9% (8/845) of all
      resected early gastric cancers. The macroscopic cancer type was elevated in 75%
      and mucosal in 88%. All were the differentiated type with no lymph node
      metastasis. The initial reconstruction involved a Billroth II in 75% of the
      patients. The RS-EGC was usually found during a periodic endoscopic follow-up.
      All patients are still alive with no postoperative complications and no cancer
      recurrence.

PMID- 8755116
TI  - Latent multiple infections by herpes simplex virus type 1.
AB  - The presence or absence of latent multiple infections with herpes simplex virus
      (HSV)-1 was investigated. DNA cleavage patterns resulting from the digestion of
      viral DNA by restriction enzymes were studied. The DNA cleavage patterns of
      asymptomatically shed viruses isolated from the saliva of subjects at different
      time were compared to HSV-1 isolated from patients with HSV-1 infections of the
      oral cavity. If a patient had HSV-1 isolated from their saliva more than two
      times, the asymptomatically shed viruses were used in these experiments. This
      criterion was met by 13 patients. All patients underwent the viral isolation
      procedure on separate occasions. In addition, 55 viral strains from 10 patients
      with HSV infections were included in the experiment. The HSV-1 lesions were
      caused by a reactivation of the same strain of virus. The asymptomatically shed
      HSV-1 viruses had identical DNA cleavage patterns in only 4 of 13 patients (31%).
      The viruses isolated on separate occasions from the remaining 9 patients (69%)
      had different DNA cleavage patterns. Several investigators have reported the
      existence of latent HSV multiple infections.

PMID- 8755117
TI  - Inhibitory effect of antineoplaston A10 and AS2-1 on human hepatocellular
      carcinoma.
AB  - Antineoplastons, first described by Burzynski, are naturally occurring peptides
      and amino acid derivatives which control neoplastic growth. Antineoplaston A10 (3
      pehnylacetylamino-2,6-piperidinedion) is the first chemically identified
      antineoplastons and when it is administered orally it is hydrolysed in pancreatic
      juice to phenylactylglutamine and phenylacetylisoglutamine in the ration of 4 to
      1. These metabolites are water soluble and have antitumor effect, they are
      further degraded to pehnylacetic acid. The mixture of phenylacetylglutamine and
      phenylacetylisoglutamine in the ratio of 4 to 1 was formulated as Antineoplaston
      A10 injectable formulation. The mixture of phenylacetylglutamine and phenylacetic
      acid in the ratio of 1 to 4 was also shown to have antitumor effect in tissue
      culture study, then formulated as Antineoplaston AS2-1. The reported cytostatic
      inhibitory effect of A10 on human hepatocellular carcinoma cells and
      differentiation inducing effect of AS2-1 on various tumor cells suggest potential
      benefit for the treatment of human hepatocellular carcinoma since this tumor
      recurs frequently despite initial successful treatment. We report here the
      effects of Antineoplaston A10 and AS2-1 on cell proliferation, cell morphology,
      cell cycle, and DNA in human hepatocellular carcinoma cell lines. Both agents
      inhibited cell proliferation and increased the number of cells in G0 and G1
      phases and Antineoplaston AS2-1 induced apoptosis, we also describe our clinical
      experience of a hepatocellula carcinoma (HCC) patient whose tumor, after
      incomplete trancathere arterial embolization (TAE) for a 7cm 7cm HCC, has been
      stable for more than 15 months during which time he has been taking
      Antineoplaston AS2-1 continuously without any serious adverse effects.

PMID- 8755118
TI  - Correlation of histology and dynamic MR imaging (MRI) of intracranial meningiomas
      with a 0.5 tesla MR system.
AB  - In 33 histologically verified intracranial meningiomas, the correlation between
      the pattern of the time-signal intensity curve (TIC) from dynamic MR imaging and
      the histological subtypes were studied. The patterns of TIC for meningiomas were
      classified into two types: type A with a steep rise to a peak within a short
      time; type B with a slow rise to a peak followed by a plateau. Of the 16
      meningiomas of the meningothelial types, 14 (87%) were type A on the TIC. On the
      contrary, all of the fibroblastic meningiomas were type B. The others had an
      almost equal distribution between the two types. These results indicate that
      dynamic MRI does not always have a predictive value for the histological subtype
      of an intracranial meningioma or for the histological architecture of the
      meningothelial or fibroblastic components.

PMID- 8755119
TI  - Immunohistochemical localization of vascular endothelial growth factor in
      esophageal cancer.
AB  - We have studied the expression of vascular endothelial growth factor (VEGF) in
      esophageal cancer using immunohistochemistry. A total of 101 specimens of
      esophageal cancer tissue were fixed by formalin, embeded in paraffin wax, and
      examined in 3 microns sections by avidin-biotin peroxidase complex method. VEGF
      was noted in the cytoplasm of normal esophageal glandular cells, monocyte
      macrophages, squamous carcinoma cells and of the vascular endothelial cells
      themselves. VEGF expression by monocyte-macrophages was observed in all cases, in
      contrast the incidence of VEGF expression in the tumor cells was relatively low
      at 26.7% of all specimens. However, in the cases where the tumor cells were
      positive for VEGF, it was discovered that the main source of the VEGF production
      was the tumor cells themselves. In the cases with proper mucosal invasion the
      incidence of VEGF expression by the tumor cells was quite low at 7.6%. However,
      when the tumor invaded the submucosal layer the expression increased to 33.3%.
      There was also a significant correlation in those with the submucosal invasion
      between the expression of VEGF in the tumor cells and that VEGF may play an
      important role in tumor progression and in the angiogenesis via auto-crine and
      para-crine mechanisms in esophageal cancer.

PMID- 8755120
TI  - Tolosa-Hunt syndrome with atypical intrasellar and juxtasellar lesions--two case
      reports.
AB  - Two patients with Tolosa-Hunt syndrome (THS) who had atypical lesions in the
      intrasellar and juxtasellar regions are reported. They manifested with painful
      ophthalmoplegia. Magnetic resonance imaging (MRI) commonly showed an increase in
      the volume of the cavernous sinus occupied by homogeneously well-enhanced lesions
      in both cases. These lesions extended to the intrasellar and juxtasellar regions
      with meningela enhancement. Follow-up MRI after steroid treatment demonstrated
      normalized or decreased size of the cavernous sinus. These findings suggested
      nonspecific inflammatory granulomatosis with atypical extension.

PMID- 8755121
TI  - Role of protein kinase in the substance P-induced inhibition of the GABA response
      in neurons of the bullfrog dorsal root ganglia.

PMID- 8755122
TI  - A rare case of the double thyroid ima artery.

PMID- 8755123
TI  - An anomalous case of the gastro-splenic and the hepato-mesenteric trunks
      independently arising from the abdominal aorta.

PMID- 8755124
TI  - Nonprostatic prostate-specific antigen.

PMID- 8755125
TI  - Prognostic evaluation of cell mediated immunity in leprosy and correlation with
      clinicopathological status of leprosy patients.
AB  - Cell mediated immunity was studied in 50 patients of leprosy and 15 control
      volunteers, by estimation of peripheral blood lymphocytes (PBL), total rosette
      forming cells (TRFC) and active rosette forming cell (ARFC) counts in vitro. PBL,
      TRFC and ARFC counts were slightly but not significantly increased in patients of
      tuberculoid leprosy (TT) and muculoanaesthetic variant of tuberculoid leprosy as
      compared to control group. However, gradual decrease in T-cell subsets, occurred
      in borderline tuberculoid leprosy (BT) as compared to tuberculoid type (TT)-(p <
      0.05). Significant decrease in lymphocytes and T-cell subsets was observed in
      midborderline leprosy (BB), (p < 0.01):borderline lepromatous leprosy (BL), (p <
      0.001) and lepromatous subpolar and polar types (LL); (p < 0.001) as compared to
      control group. Mycobacterium leprae (M.leprae) were positive in BT-(20%); BB
      (72.7%); BL-(83.2%) and LL-(100%). Delayed hypersensitivity reactions (DHR)
      revealed significantly increased lepromin positivity in TT (83.3%) and BT (80%)
      which decreased in BB (63.6%) and BL (50%). Lepromin test showed anergic state in
      LL group (28.5% positivity). Dinitrochlorobenzene (DNCB) skin test showed 100%
      positivity in TT group and controls while gradual significant decrease was
      observed from BT (p < 0.05) to LL scale (p < 0.001). Leprosy spectrum of Ridley
      and Jopling scale is directly co-related with inherent cell mediated immune
      status of the patients which has a significant prognostic role in treatment and
      long term management.

PMID- 8755126
TI  - Role of immunophenotyping in characterisation of blast crisis of chronic myeloid
      leukemia--a study of 25 cases.
AB  - The blast cell populations of 25 patients of chronic myeloid leukemia in blast
      crisis (CML-BC) were studied for morphological, cytochemical and immunophenotypic
      features. The patients were divided into 6 broad groups based upon the pattern of
      surface marker positivity-myeloblastic, mixed myeloblastic, megakaryoblastic,
      mixed lineage, lymphoid and undifferentiated blast crisis. Myeloperoxidase (MPO),
      Sudan Black B (SBB) and Chloroacetate esterase (CAE) stains showed 100%
      specificity for the myelomonocytic lineage but the sensitivity was low. Periodic
      acid Schiff (PAS) stain was neither specific nor sensitive for the lymphoid
      lineage. Immunophenotyping as compared to morphologic and cytochemical
      assessment, was seen to be most useful for assigning a lineage to leukemic cells
      in CML-BC.

PMID- 8755127
TI  - HLA class-I and class-II antigen association in rheumatoid arthritis at Varanasi,
      India.
AB  - Clinical presentation of rheumatoid arthritis (RA) and its severity differs in
      different races. Genetic factors play a significant role in its predeliction. The
      present study was undertaken to find out association of HLA class I and class II
      antigens with rheumatoid arthritis prevalent in Asian Indians residing at
      Varanasi. Ninety rheumatoid arthritis patients strictly fulfilling American
      Rheumatism Association criteria were screened for prevalent HLA class I and class
      II antigen by Terasaki Microlympho-cytotoxicity test. Results were compared with
      100 healthy controls and 35 Seronegative Spondyloarthritides cases (SSA).
      Rheumatoid arthritis patients showed increased frequency of HLA-A2 and B40
      antigens compared to healthy controls (p < .001). SSA patients showed
      significantly increased Phenotype frequency (PF) of HLA-B27 (p < .0001) and B40
      (p < .001). Significant detection of HLA-A2 exclusively in RA patients suggests a
      more positive association of A2 in rheumatoid arthritis at Varanasi. HLA-B40
      could not be attributed absolute significance of association with SSA or RA as it
      showed increased frequency in both diseases.

PMID- 8755128
TI  - Sequential study of IgG antibody response in immunized rabbit and development of
      immunization protocol for raising monospecific antibody.
AB  - The present study was planned to develop an immunization protocol to decide the
      bleeding modalities for harvesting anti IgG antibody from the immunized rabbit. A
      fourteen dose immunization protocol (four primary and ten boosters) of the
      purified human IgG spread over the one calendar year was executed. The antibody
      titre estimated by Reverse Single Radial Immunodiffusion displayed a six-phased
      pattern. The titre following the initial immunization ranged between nil to 1.02,
      characteristic of the primary response while the titres after 7th and 8th
      boosters (phase V) ranged between 0.5 to 3.87 consistent with secondary response.
      Phase II, III, IV had moderately elevated titres. The antibody titre amongst the
      six phases reached to its peak generally by the 12th day after the last dose of
      protocol and it took about 60 days to reach to its basal level. Administration of
      antigen with the higher levels of residual antibody did not produce high titre
      antibody and is probably ascribed to elimination of antigen through an
      immunecomplex mechanism. Based on the data we recommend that 15 batches. (3 per
      phase, phase I to phase V) with a total yield of 100 to 120 ml of serum can be
      procured from one immunised animal over the span of one calendar year and that
      should make the programme cost effective.

PMID- 8755129
TI  - Incidence of anaerobic bacterial infection following transurethral
      instrumentation.
AB  - Total 300 patients undergoing transurethral instrumentation had their urine
      culture for aerobic and anaerobic organism pre-operatively and post-operatively.
      An increase in the incidence of anaerobic urinary tract infection from 2% pre
      operatively to 14% post-operatively following transurethral instrumentation was
      documented. It was concluded that transurethral instrumentation increases the
      incidence of anaerobic urinary tract infection and patients having symptoms of
      urinary tract infection following such procedures with sterile urine for aerobic
      bacteria should be studied and treated appropriately for anaerobic urinary tract
      infection.

PMID- 8755130
TI  - Pigmented dermatofibrosarcoma protuberans (Bednar tumour).

PMID- 8755131
TI  - Nurse executive. Communities and big white buildings.

PMID- 8755132
TI  - Public policy. The urge to merge--will quality survive?

PMID- 8755133
TI  - Research. A missing research tradition.

PMID- 8755134
TI  - Using computerized clinical nursing data bases for nursing research.
AB  - Computerized clinical nursing data bases (CCNDBs) have significant potential as
      sources of data for research on the processes and outcomes of nursing care. The
      emergence of nurse-managed practice sites, in which patient care is driven
      predominantly by nurses' decisions, has prompted renewed interest in using data
      from these practices to answer questions that are important to nurses. The
      purpose of this article is to articulate strategies for using CCNDBs for nursing
      research. Recognition of the differences between clinical and research data bases
      is essential. The steps involved in obtaining and using computerized clinical
      data can be grouped into three phases: (1) locating and accessing CCNDBs, (2)
      assessing the content and quality of the data, and (3) extracting and analyzing
      the data. Processes involved in phase 1 include determining the research
      question, identifying eligible CCNDBs, negotiating access to the CCNDB, and
      ensuring the privacy and confidentiality of subjects. In phase 2 the processes
      include determining the content of the candidate CCNDBs, assessing the quality of
      the data in candidate CCNDBs, and determining the technical usability of data in
      candidate CCNDBs. Phase 3 involves mapping CCNDB data elements to research
      variables; determining data and record selection criteria; writing and
      implementing a query to select the desired records; designing a data base and
      record structure for research variables; performing analytic procedures on the
      research data; and reporting results of the research. Phases and procedures are
      discussed in detail in the article.

PMID- 8755135
TI  - Patient satisfaction with nursing care as an outcome variable: dilemmas for
      nursing evaluation researchers.
AB  - Evaluation is one of the most critical phases of the nursing process because it
      supports the basis of the usefulness and effectiveness of nursing practice.
      Nursing practice is patient driven and patient centered. Accordingly, patient
      satisfaction has been strongly advocated by nursing professionals to be an
      important indicator of quality of nursing care delivery. This article discusses
      the conceptualization and measurement of patient satisfaction with nursing care.
      Also, this article examines numerous dilemmas related to conceptualization and
      methodology that nursing evaluation researchers confront when attempting to use
      patient satisfaction as an outcome variable. Based on the current knowledge
      regarding the nature of patient satisfaction, implications for future nursing
      evaluation research are proposed and discussed to overcome these dilemmas in
      measuring patient satisfaction as an indicator of quality of nursing care.

PMID- 8755136
TI  - Factors associated with student nurses' intent to provide physical and
      psychosocial care to persons with acquired immunodeficiency syndrome.
AB  - This project examined the influence of selected factors on student nurses' intent
      to provide physical and psychosocial care to persons hospitalized with acquired
      immunodeficiency syndrome (AIDS). Respondents were 125 undergraduate upper
      division nursing majors attending a state-supported university. Questionnaires
      were distributed to student mailboxes and were returned anonymously through the
      United States Postal Service. All factors were correlated with intent to provide
      physical care and with intent to provide psychosocial care using Pearson product
      moment correlation coefficients. For both intention scales, attitude toward a
      person with AIDS acquired through homosexual activity and attitude toward a
      person with AIDS acquired through sharing needles were positively related to
      intent to provide care. Homophobia, fear of AIDS, and perceived susceptibility
      toward acquiring human immunodeficiency virus from providing care were inversely
      related. These findings are useful for designing programs that promote the
      delivery of compassionate nursing care to persons with AIDS.

PMID- 8755137
TI  - Attitudes of baccalaureate nursing students toward persons with acquired
      immunodeficiency syndrome according to mode of human immunodeficiency virus
      transmission.
AB  - The purpose of this descriptive correlational study was to (1) examine
      differences in baccalaureate nursing students' attitudes toward persons living
      with acquired immunodeficiency syndrome (AIDS) (PLWAs) according to mode of
      transmission and (2) identify demographic and academic variables influencing
      baccalaureate nursing students' attitudes toward PLWAs. Two hundred forty-six
      students from five geographically dispersed baccalaureate programs returned a
      completed demographic data sheet, AIDS Knowledge Scale, and AIDS Attitude Scale.
      The AIDS Attitude Scale, based on Goffman's theory of stigma, assesses
      stigmatizing attitudes, perceptions of deservedness of care, and attitudes of
      respect and regard for PLWAs according to five modes of human immunodeficiency
      virus transmission. The findings of this study demonstrated overall that
      baccalaureate students were the most stigmatizing toward persons who had
      developed AIDS through injecting drugs followed by sexual contact (both
      homosexual and heterosexual) and least stigmatizing toward PLWAs who contracted
      the virus through maternal transmission or a blood transfusion. Perhaps the PLWA
      who contracted AIDS through either maternal transmission or a blood transfusion
      was viewed as an "innocent victim" of the disease, whereas PLWAs who contracted
      the virus through either shared needles or sexual transmission were viewed as
      having acquired the infection through the results of their actions. The
      demographic characteristics of the respondents did not influence AIDS attitudes.

PMID- 8755138
TI  - Empowerment of graduate nursing students: a dialogue toward change.
AB  - This article represents the first phase in exploration of empowerment of graduate
      advanced practice nursing students. This phase includes a review of the relevant
      literature on empowerment and discusses the applicability of this literature to
      current educational practice. The authors suggest that creating an empowering
      environment for learning necessitates dramatic change in teaching methodology and
      in faculty-student perspective about their roles. An ongoing dialogue among
      faculty and between students and faculty is proposed to begin to conceptualize
      this change. This article also presents a synopsis of a dialogue between the two
      authors intended to stimulate further discussion.

PMID- 8755139
TI  - Professional image: enhanced or inhibited by attire?
AB  - Nursing faculty have expressed concern about inappropriate dress of students and
      staff in the clinical setting. The researchers developed and administered a
      Likert-type questionnaire to faculty and students from 50 randomly selected,
      National League for Nursing-accredited baccalaureate nursing programs. The
      perceptions of professional attire of students and faculty were compared and
      analyzed. The tool assessed effects of demographic variables, such as age,
      gender, and curriculum level. In addition, questions assessed subject's opinions
      about attire options such as jumpsuits, "scrubs," tee-shirts, sweatshirts,
      hemlines, traditional white uniform, street clothes, hair length, jewelry, and
      nail length. Attire preferences significantly correlated with faculty age and
      teaching level. The older faculty preferred more traditional attire, and faculty
      in the upper division of the curriculum preferred more nontraditional attire.
      This same correlation was found for older students and for students enrolled in
      the upper division. Faculty influence on students' perceptions of attire was also
      addressed. Students reported that faculty positively influenced their perceptions
      of professional image. Students also believed that faculty were professionally
      attired in the classroom and clinical setting.

PMID- 8755140
TI  - Iowa nurses' knowledge of living wills and perceptions of patient autonomy.
AB  - The principle of patient autonomy is well recognized in the nursing profession.
      This study extends the exploration of patient autonomy by examining nurses'
      knowledge about living wills. The questions addressed in this study included the
      following: (1) Were Iowa nurses aware of the living will statute? (2) What
      sources of information did nurses use to learn about this legislation? (3) What
      were nurses' perceptions of patients' rights? (4) What were nurses' perceptions
      of nurses' role involving living wills? (5) Were living wills followed? (6) If
      not followed, which factors contributed to the failure to honor a living will?
      and (7) Which communication mechanisms were used to alert nurses to a living
      will? A questionnaire was mailed to 10,000 actively licensed nurses in Iowa.
      Approximately 3,000 Iowa nurses responded to the questionnaire regarding Iowa
      living wills. Seventy per cent of the nurses knew that Iowa had living will
      legislation. No single educational source was a predominate choice for targeted
      information about the living will statute. Nurses were reluctant to suggest to
      patients that they should consider writing a living will. Nurses were also more
      willing to assume a passive role of suggesting that patients talk with relatives
      about the need for a living will but were less likely to be suggest that a
      patient write a living will for future health care treatment decisions. The
      majority of the nurses favored the patient having some control in health care
      treatment decisions. Three major factors were pertinent to the failure to follow
      a living will: family request, treating physician's refusal, and lack of
      information that the living will existed. The medical record was the primary
      means of communication regarding a living will. To enhance patient efforts at
      self-determination, nurses must recognize the advance directive legislation is
      available in their state and the potential impact that their nursing care may
      have on the implementation of the document.

PMID- 8755141
TI  - Policy and guidelines for prevention and management of substance abuse in the
      nursing education community. American Association of Colleges of Nursing.

PMID- 8755142
TI  - [Anti-infective defence strategies and methods of escape from entomologic
      pathogens under immunologic control of insects].
AB  - Insect immunity comprises a complex of several distinct systems, both haemocytic
      and humoral in nature, that cooperate together in a more or less coordinated way
      to provide protection of the body cavity from invading microorganisms. Insects
      can respond to infections by a selective synthesis of haemolymph immune proteins
      that are responsible for antibacterial immunity. Antibacterial activity of insect
      blood is attributable to innate compounds such as lysozome, and to induced
      polypeptides or small basic proteins absent in non-immunized insects. The
      cecropins and attacins in Lepidoptera, and diptericins in Diptera are the
      inducible antibacterial immune proteins well defined biochemically. Bacterial
      pathogens and some parasites of insects, preferably entomogenous rhabditid
      nematodes, have developed the mechanism by which they may counteract insect
      immunity. This phenomenon is realized either by escaping immune reactions or by
      degrading antimicrobial factors of haemolymph in an active process. Passive
      resistance of parasites to insect immunity is a result of a strong evolutionary
      pressure on parasites to develop mechanisms to escape insect immune reactions or
      to minimize their effectiveness through changes in the parasite itself. Active
      resistance to the insect non-self response system involves a partial or total
      destruction of immune proteins by extracellular proteinases released during
      parasitism.

PMID- 8755143
TI  - [Biological monitoring with regard to parasites].
AB  - The paper deals with the discussion on the sozological aspects of parasitology in
      the context of environmental monitoring, particularly the role of parasites as
      indicators of environmental quality bio-assessment. Parasites and parasitological
      rules are also suspected to have great weight with the study of biology, ecology
      and evolutionary relations between hosts in different ecosystems. It can be done
      by tracing the changes among host-parasite relationships and investigations of
      host and biotope condition.

PMID- 8755144
TI  - [Protozoa as reservoirs for human bacterial pathogens].
AB  - The ability of bacterial pathogens to survive within the human host cells results
      from their evolutional adaptation of which the most important stage could be the
      development of parasitic relations between bacteria and free-living protozoa.
      This paper shows the bacterial species, pathogenic for man, surviving in
      protozoans cells.

PMID- 8755145
TI  - Propionibacterium granulosum activities in rats during the muscle phase of
      Trichinella spiralis invasion.
AB  - Immune response of Wistar rats, infected with 4000 L1 T. spiralis and treated
      with P. granulosum during the muscle phase of nematode invasion were measured.
      The increase of spleen mass was observed in all groups infected and exposed to P.
      granulosum. Intraperitoneal injection of bacteria results in higher level of T
      lymphocytes and activated neutrophils. The level of inhibition of macrophages
      migration was depended on relation to the time and doses of injection. In non
      specific stimulated animals there were not statistically significant changes in
      the level of specific IgG1 antibodies determined by ELISA, against the crude
      extract of infective larvae of T. spiralis. The reduction of intensity of
      nematode invasion during the muscle phase was not observed in rats after P.
      granulosum treatment.

PMID- 8755146
TI  - [Phosphocholine antigens in muscle larvae of Trichinella spiralis].
AB  - Crude T. spiralis larval antigens often cross-react with antibodies to other
      parasites (for instance Toxocara canis) in the ELISA test. The crossreactivity of
      the sera is probably due to the presence of phosphocholine (PC)-specific
      antibodies to antigens found in the inner layer of the cuticle, in the
      haemolymph, genital primordium and glycogen aggregates T. spiralis larvae. The
      anti-PC response following infection with T. spiralis occurs earlier than the
      antispecific antigens response. The above data suggest a possibility that some
      results of immunoenzymatic examination for trichinellosis may be false positive.
      The necessity of WESTERN blot verification of weakly positive results in the
      ELISA test seems to be obvious. There is a need to improve serological diagnosis
      of trichinellosis by applying alternative tests that would aid an early diagnosis
      of the infection such as those for circulation parasite antigens or parasite DNA.

PMID- 8755147
TI  - [The influence of various levels of carotene and protein in the diet on the index
      of invasion and digestive enzyme activity in chickens infected with Ascaridia
      galli].
AB  - Chickens 10 days old were infected with 500 eggs of Ascaridia galli. They were
      fed with diet containing 11% or 19% protein. Some of them were given beta
      carotene in a dose equivalent to daily requirement of vitamin A, others were
      given double dose of beta-carotene. The intensity and extensity of invasion, the
      body weight, and activities of alpha-amylase, lipase and trypsin in pancreas and
      duodenal content were measured. Application of beta-carotene (especially in a
      double dose) caused the decrease in the invasion index and moderated the changes
      in the activity of digestive enzymes, occurring in the infected chickens.

PMID- 8755148
TI  - [Investigations on the pathogenesis of changes in somatic growth of Lymnaea
      stagnalis (Gastropoda: Pulmonata) experimentally infected with parthenites
      Opisthioglyphe ranae (Digenea: Plagiorchiida). I. Relative weight of accessory
      sex organs and synthetic activity of neurosecretory cells].
AB  - In the paper an attempt to define pathogenesis of changes in somatic growth of
      juvenile individuals of the popular freshwater snail Lymnaea stagnalis
      experimentally infected with parthenites of the trematode Opisthioglyphe ranae
      was undertaken. Significant enlargement of relative wet weight of examined
      accessory sex organs (albumen gland, oothecal gland, prostate, male copulatory
      organ) observed in infected snails permits to explain increase of their somatic
      growth basing on the hypothesis of disturbances in energetistic budget of the
      host-as a consequence of reduction by the parasite activity of the snail's
      reproductive system. Pathogenesis of this phenomenon has probably a complicated
      character, including also effect of parthenites on activity of the neurosecretory
      cells that control somatic growth in examined species of the snail. An argument
      for this standpoint is, observed in infected snails, increase of amount of
      neurosecretory material and RNA in cytoplasm of these cells (the light green
      cells of cerebral ganglia), as well as amount of the loose fraction of chromatine
      in their nuclei.

PMID- 8755149
TI  - [Comparative studies on the ultrastructure, homology and analogy of egg envelopes
      in trematodes and cestodes].
AB  - The origin, differentiation and functional ultrastructure of egg envelopes
      surrounding developing and mature miracidia of Schistosoma mansoni and that of
      developing and mature coracidia of Bothriocephalus clavibothrium have been
      examined by means of electron microscopy and cytochemistry. Results obtained on
      these two species were compared with data from our previous studies on the
      ultrastructure of egg envelopes in different cyclophyllidean (Hymenolepididae,
      Taeniidae, Anoplocephalidae, Davaineidae) and proteocephalidean cestodes. In the
      mature infective egg, the three main egg envelopes (the egg-shell, and the outer
      and inner envelope) that surround the larvae (miracidia of Digenea, coracidia of
      Pseudophyllidea, and hexacanths of Cyclophyllidea and Proteocephalidea), show
      evident similarities in their origin, functional ultrastructure and chemical
      composition. Conclusions of this comparison, concerning analogy and homology in
      egg envelopes of trematodes and cestodes, are drawn and discussed.

PMID- 8755150
TI  - [Hereditary character of feature variability in Hymenolepis diminuta bred from
      oncospheres of defined origin].
AB  - Three groups of tapeworms obtained 2.5 month after the administration to rats of
      a dose of 6 cysticercoids proceeding from oncospheres of the 24th generation of
      Hymenolepis diminuta were compared. Group I came from the oncospheres of only one
      proglottid of H. diminuta WMS "strain" tapeworm. Group II proceeded from 6
      proglottids obtained each from another tapeworm of this "strain". Group III came
      from 6 proglottids, each from another tapeworm of H. diminuta WMS inbred line 1
      (il1). The average number of type 0p3a proglottids in group I and II was similar
      and amounted to 4.0% and 4.7%, respectively, while in group III it was
      significantly higher than in the first two groups and reached an average of 8.4%
      (P < 0.01). There are also other significant differences between the two breeding
      lines-H. diminuta WMS "strain" and WMS il1 with respect to the number of typical
      1p2a proglottids, type 1p3a proglottids, the second after 0p3a most common
      deviation from the typical 1p2a as well as all deviations taken together. This
      points to the influence of different breeding condition: non-inbred in case of H.
      diminuta WMS "strain" and inbred in case of H. diminuta WMS il1 on the
      investigated features.

PMID- 8755151
TI  - Demodex bisonianus sp. nov. (Acari, Demodicidae) a new parasite of the bison
      (Bison bonasus L.).
AB  - Demodex bisonianus sp. nov. (Acari, Demodicidae) and its stages of development
      has been described. It was found in the Meibomian glands of the Bison bonasus L.
      from the Puszcza Bialowieska (Poland).

PMID- 8755152
TI  - [Allergenic mites found in raw material of herbs based on literature about the
      Pyroglyphidae (Acari: Acaridida)].
AB  - The occurrence of two pyroglyphid mites. Euroglyphus maynei (COOREMAN, 1950) and
      Dermatophagoides pteronyssinus (TROUESSART, 1897) in the raw material of herbs is
      discussed and compared with the literature data. These mites are considered to be
      the cause of human atopic diseases.

PMID- 8755153
TI  - [Dr Med. Alexander Rydzewski (obituary)].

PMID- 8755154
TI  - [Prof. Dr. hab. Wanda Stojalowska (obituary)].

PMID- 8755155
TI  - [Alcohol measurement in traffic accidents: how long will the ostrich strategy
      last?].

PMID- 8755156
TI  - [Alcohol level and injury risks in traffic accidents in Tudela (Navarre)].
AB  - OBJECTIVE: A case-control study was carried out with the aim of assessing the
      association between the levels of blood alcohol in drivers and traffic accident
      rate. METHODS: 150 cases of drivers injured in traffic accident were obtained,
      treated at the Emergency Medical Services of the Hospital Comarcal of Tudela
      (Navarre) and whose alcohol level in blood was determined with the ADX technique
      and compared to the 648 controls from a representative sample among the drivers
      from the area, whose alcohol level in exhaled air was assessed with a digital
      alcoholometer. The research was carried out in the period between 1 May, 1990 and
      30 April, 1991. RESULTS: In the injured drivers. (cases) the prevalence of blood
      alcohol levels equal or over 50 mg/dl was 36.6%, compared to 6.9% in controls.
      The odds ratio for blood alcohol levels equal or over 50 mg/dl. compared to
      levels below 50 mg/dl was 7.5.

PMID- 8755157
TI  - [Prevalence of Down's syndrome in Asturias, 1987-1993. Members of the Work Group
      of the RCDA].
AB  - OBJECTIVE: To determine the frequency of Down Syndrome (DS) in Asturias and the
      prenatal diagnosis impact on the birth prevalence of this chromosomal anomaly.
      METHODS: The analysed data came from the Registry of Congenital Defects of
      Asturias (1990-1993) and from a retrospective study conducted by the same working
      group (1987-1989). The total prevalence rates and the prevalence at birth were
      calculated. RESULTS: Out of 55,601 births, DS was recorded in 83 cases: 69
      livebirths, two fetal deaths and 12 induced abortions following prenatal
      diagnosis, giving a total prevalence rate of 14.9 per 10,000 and a birth
      prevalence of 12.8. The proportion of induced abortions was 15 per cent in this
      period; the proportion of cases in the high risk maternal age group (35 years and
      over) was around 50% of the total. The proportion of induced abortions was 15 per
      cent in this period. CONCLUSIONS: The frequency of DS in Asturias is comparable
      to the other populations. Prenatal diagnosis had little impact on the birth
      prevalence figures. These results may help us draw up prevention and prenatal
      diagnosis policies for these defects in Asturias when giving the frequency of
      this health problem.

PMID- 8755158
TI  - [Trends in cervix cancer mortality in Catalonia, 1975-1992: analysis of death
      certificates and cancer registry of Girona].
AB  - INTRODUCTION: Uterine cancer not otherwise specified (NOS) is often recorded in
      death certificates as cause of death. The purpose of the study is to recode all
      death certificates mentioning gynecological cancers in the area of Girona, Spain
      and to compare trends in cervical cancer mortality before and after
      recodification. METHODS: Death certificates issued between 1985 and 1989 in the
      province of Girona (population 500,000) mentioning gynecological cancer were
      identified. Medical records and the files of the local Cancer Registry were
      reviewed to assess the accuracy of the diagnosis and to recode the appropriate
      site of the primary. The resulting distributions were then applied to the
      mortality statistics of Catalonia (population 6,000,000 including Girona) and
      mortality trends were analyzed. RESULTS: Uterus NOS were reclassified as follows:
      cervix uteri 24%, corpus 29%, ovary 13%, other 14%. In 20% of the cases the code
      remained as uterus NOS. When this distribution was applied to the Catalan
      mortality statistics for 1975-1992, a downward trend was observed for cervical
      cancer at all age groups. CONCLUSIONS: About one third of uterus NOS in death
      certificates corresponded to cervix and one third to corpus. Mortality trends are
      severely affected by the proportion of certificates coded as uterus NOS. There is
      no indication of an increase in cervical cancer mortality among young women in
      Catalonia.

PMID- 8755159
TI  - [A sickness called unemployment: a long-term unemployment. Association of
      Community Development (ACD)].
AB  - OBJECTIVES: The general objective of this investigation is to know the possible
      consequences of long-term unemployment on the family and social environment, as
      well as the mechanisms which lead to the appearance of health problems among long
      term unemployed people. METHODS: The subjects of this study were long-term
      unemployed people of 35 to 55 years of age of the municipal term of Madrid, with
      families depending on them. This is a qualitative-intensive investigation, with
      special emphasis on the individual, social, sanitary and economical aspects. The
      instrument of common measurement was the combination of the discussion group
      integrated by five people, during approximately 120 minutes, with focused and
      individual interviews (48) over a semistructured script, during approximately 60
      minutes, using recording instruments (audio tape). RESULTS: During the
      development of the discussion group a worsening of the psychological health and
      family situation was observed as a consequence of remaining unemployed. In the
      more thorough interviews we could detect clear differences according to the
      impact of unemployment on health depending on the low socioeconomical area, women
      and older unemployed people. CONCLUSIONS: The effects of unemployment on health
      cannot be isolated from other underlying bad social and economical conditions,
      that is to say, from social, economical, educative inequalities, etc., previous
      to the unemployment situation.

PMID- 8755160
TI  - [Advertising of drugs: risk or benefits?].
AB  - It is obvious how important is the role of the physicians on drugs consumption.
      On account of their intermediary in the procurement and consumption of medicines,
      the prescriber is the main focus of manufacturers' promotional activities aiming
      at increasing sales and profits although these activities often are disguised as
      a means of education or information. Many reports have been issued emphasizing
      the influence of commercial sources upon the prescription. This text reviews two
      of them -advertisements in medical journals and the representatives- arriving to
      the conclusion that first ones display informations that are biased and
      incomplete while the representative in fact acts as a sales agent. The
      professional sources of information for prescribers are also described being
      evaluated how far-reaching the sources referred can be.

PMID- 8755161
TI  - [Research: why, for whom and when?].

PMID- 8755163
TI  - Stability of transgene methylation patterns in mice: position effects, strain
      specificity and cellular mosaicism.
AB  - The methylation status of a transgene, which carried the adenovirus type 2 E2A
      late promoter linked to the chloramphenicol acetyltransferase gene, was studied
      in three transgenic mouse lines (5-8, 7-1 and 8-1). These lines were analysed
      over a large number of offspring generations beyond the founder animal. In mating
      experiments, the influence of the parent-of-origin and strain-specific
      backgrounds on the transgene methylation patterns were assessed and found to have
      no effect on the pre-established methylation patterns in mouse lines 5-8 and 8-1.
      The founder animal 7-1 carried two groups of a total of ten transgenes, which
      were located on two different chromosomes. These arrays of transgenes could be
      segregated into separate mouse lines 7-1A and 7-1B. The transgenes of 7-1A
      animals exhibited cellular mosaic methylation patterns that were demethylated in
      approximately 10% of the offspring in a mixed genetic background. Upon further
      transmission of these transgenes in a mixed genetic background, the grandparental
      methylation patterns were reestablished in most progeny. Mating to inbred DBA/2
      mice resulted in maintenance of the demethylated pattern or in further
      demethylation of the transgenes in approximately 50% of the offspring. In
      contrast, an equal number of transgenic siblings from matings to C57BL/6 mice
      showed a return to the original methylation pattern. The mosaic methylation
      status of this locus was apparently controlled by mouse-strain-specific factors.
      The methylation patterns of the 7-1B transgenes were not cellular mosaic and
      remained stable in all offspring, as with lines 5-8 and 8-1. Hence, the strain
      dependent and cellular mosaic transgene methylation patterns of 7-1A animals were
      probably a consequence of the chromosomal integration site of the transgenes
      (position effect).

PMID- 8755162
TI  - Transgenesis in rats: technical aspects and models.
AB  - The production of transgenic rats by DNA-microinjection into fertilized ova has
      now become an established procedure, although fewer than 20 lines have been
      described during the last 5 years. Overall, transgenic rats remain more difficult
      to produce than transgenic mice, but satisfactory yields have been obtained by
      several laboratories. A review of the methods used to generate transgenic rats
      shows considerable variation between different laboratories, particularly in
      choice of strain, superovulation protocols and the use of embryo culture before
      reimplantation. In some instances, the production of transgenic rats has provided
      data that are new and relevant, compared to data obtained in mice bearing the
      same transgene. Models have been developed for human diseases such as
      hypertension and autoimmunity, and applications have been found in the study of
      carcinogenesis and in pharmacological research. Transgenic rat technology also
      opens up interesting perspectives for transplantation research, in which
      microsurgery is an essential procedure. Intensive research is in progress in
      several laboratories to produce rat embryonic stem (ES) cell lines, but existing
      lines have not participated in germ line formation a prerequisite for their use
      in gene knock out experiments.

PMID- 8755164
TI  - Analysis of developmental switching in transgenic mice with 5' and 3' deletions
      in the human beta globin gene.
AB  - Our interest in the cis-acting elements that promote the up-regulation of the
      beta globin gene has led to a systematic deletion analysis of portions of the
      beta globin gene in the context of the HS2 and gamma globin gene using transgenic
      mice. In constructs that delete the 5' region to only 265 bp, high-level,
      erythroid-specific expression was observed. Further deletion to 122 bp, however,
      results in significantly reduced expression levels. A substitution of a minilocus
      control region for the single HS2 site was also produced, resulting in increased
      beta globin expression over that seen with the HS2 alone. These results are
      consistent with the presence of an enhancer-like element between -122 and -265.
      In addition, a construct in which the entire beta globin gene promoter was
      replaced by a thymidine kinase promoter was tested. Interestingly, no expression
      was detected in these transgenic mice. This may indicate the requirement for an
      erythroid-specific promoter to drive this gene. Finally, the 3' region of the
      beta globin gene was deleted in order to examine the effect of a previously
      defined 3' enhancer region. With deletion of this region, the expression of the
      human beta globin gene in transgenic mice is unchanged relative to the parental
      constructs.

PMID- 8755165
TI  - Strategies for the suppression of peroxidase gene expression in tobacco. I.
      Designing efficient ribozymes.
AB  - Five short hammerhead ribozymes (Rzs) were constructed and tested, using a range
      of in vitro reaction conditions, for catalytic activity against the mRNA encoding
      the lignin-forming peroxidase (TPX) of tobacco. Although all 5 Rzs were shown to
      be able to cleave the RNA substrate, percentage cleavage varied with pre
      denaturation of Rz and substrate, incubation temperature, length of incubation
      and ribozyme (Rz)-to-substrate ratio. One Rz with two catalytic units and 60
      nucleotides of complementary sequence in 3 regions was shown to most efficiently
      cleave the substrate under all in vitro conditions tested. This ribozyme cleaved
      better than the two single ribozymes from which it was made. The superior
      cleaving ability of this Rz was shown to be due to the accessibility of the
      chosen target site and to the increased length of the hybridizing arms spanning
      this accessible region of the RNA.

PMID- 8755168
TI  - Rotavirus and non-febrile convulsions.

PMID- 8755166
TI  - Strategies for the suppression of peroxidase gene expression in tobacco. II. In
      vivo suppression of peroxidase activity in transgenic tobacco using ribozyme and
      antisense constructs.
AB  - Several strategies involving the use of antisense and ribozyme constructs in
      different expression vectors were investigated as methods of suppressing gene
      expression in planta. We had previously identified an efficiently cleaving
      ribozyme (Rz), with two catalytic units and 60 nucleotide (nt) of complementary
      sequence, to the lignin-forming peroxidase of tobacco (TPX). This Rz was cloned
      behind the 35S CaMV (35S) and nopaline synthase (NOS) promoters, and into a
      vector utilising the tobacco tyrosine tRNA for expression. For comparison with
      more traditional antisense strategies, full-length TPX antisense (AS) constructs
      were also constructed behind the NOS and 35S promoters. Populations of transgenic
      tobacco containing these constructs were produced and compared to control plants
      transformed with the vector only. Significant suppression of peroxidase
      expression in the range of 40-80% was seen in the T0 and T1 populations carrying
      35S-AS, 35S-Rz and tRNA-Rz constructs. Co-segregation of the suppressed
      peroxidase phenotype and the tRNA-Rz transgenes was demonstrated. Northern blot
      analysis indicated that levels of TPX mRNA were lower in the Rz plants. No
      evidence of mRNA cleavage was observed and thus it was unclear if the Rz
      constructs were acting as Rzs in vivo. Transgenic plants containing the tRNA-Rz
      construct had significantly lower levels of peroxidase than the other transgenic
      plants. There was no significant difference in levels of suppression of TPX
      between the short Rz in the 35S vector and the full-length AS constructs.
      Although peroxidase levels were significantly reduced in transgenic plants
      carrying 35S-AS, 35S-Rz and tRNA-Rz constructs, no significant difference in
      lignin levels was observed.

PMID- 8755167
TI  - Expression of a bovine kappa-CN cDNA in the mammary gland of transgenic mice
      utilizing a genomic milk protein gene as an expression cassette.
AB  - Transgenic mice were produced by microinjection of a DNA construct composed of
      the bovine kappa-casein (kappa-CN) cDNA under the control of the goat beta-CN 5'
      promoter elements and 3' flanking regions into pronuclear-stage embryos. The gene
      construct targeted the expression of bovine kappa-CN RNA to the mammary gland and
      secretion of bovine kappa-CN in the milk. In the three lines studied (BC-7, BC-31
      and BC-67) the transgene was stably integrated and propagated as a Mendelian
      locus. Expression of the bovine protein in lactating mice from the three
      transgenic lines was demonstrated by northern and western blots. In ten different
      tissues analysed by northern blotting, expression was confined to the mammary
      gland of lactating transgenic mice from line BC-7, with low-level expression also
      observed in the salivary gland of lines BC-31 and BC-67. Transgene expression in
      the mammary gland paralleled normal casein gene expression during lactation and
      was not observed in virgin females. The level of bovine kappa-CN mRNA expression
      on day 10 of lactation in hemizygous transgenic females in relation to endogenous
      mRNA of whey acid protein (WAP) gene expression was 14%, 69%, and 127% in lines
      BC-7, BC-31 and BC-67, respectively. No association between transgene copy number
      and expression was observed. The bovine kappa-CN concentration in milk on day 10
      of lactation ranged from 0.94 to 3.85 mg of protein per ml of milk. The bovine
      kappa-CN expressed in mouse milk had the same molecular mass and immunoactivity
      with polyclonal antibodies as did kappa-CN from bovine milk. A high degree of
      variation in the production of bovine kappa-CN within each of the transgenic
      lines was observed.

PMID- 8755169
TI  - Prevention of birth defects: a task for a world alliance.

PMID- 8755170
TI  - Torticollis: a long-term follow-up study.
AB  - To achieve better guidelines for the future management of torticollis, this study
      analyzed surgical and nonsurgical management of 253 torticollis patients who were
      treated in this hospital from 1971 to 1993. Of those, 37 cases received operation
      only, 78 cases were operated after failed physical therapy, and 138 cases were
      treated only at the Rehabilitation Department. If free neck movement was
      considered to be the primary goal of treatment, most parents were satisfied with
      the results. However, if facial and skull deformities were the serious sequelae
      of torticollis, then only less than half of the surgical and nonsurgical groups
      of patients were graded as normal. Further, 10.9% of physical therapy group and
      7% of the surgical patients need further operation to release the fibrotic bundle
      which limited their neck movement. Therefore, it is suggested that torticollis
      treatment should include early interventions such as adjusting sleep position,
      careful planning of physical therapy and/or operation and a long term follow-up
      period as essential for better management of torticollis.

PMID- 8755172
TI  - Sex determination in infants with ambiguous genitalia using the polymerase chain
      reaction of an X-Y homologous region.
AB  - A polymerase chain reaction (PCR) technique applicable for sex identification is
      described. The technique amplifies a part of the X-Y homologous amelogenin gene
      in which the Y counterpart has a 189 bp deletion within one of the introns. To
      evaluate the value of PCR of a X-Y homologous region in sex determination,
      individuals with ambiguous genitalia were selected for study. By identification
      of the X and Y sequences based on the difference in their sizes, sex
      determination could be successfully made.

PMID- 8755171
TI  - Bony changes in common mucopolysaccharidoses.
AB  - To evaluate the radiological features of mucopolysaccharidoses (MPS), 15 cases
      were collected for review in this hospital, retrospectively (1985-1995). Eight
      cases of Hurler syndrome, two cases of Hunter syndrome, two cases of Sanfilippo
      syndrome and three cases of Morquio syndrome were classified. Varying severity of
      dysostosis multiplex is the general bony manifestation of MPS, but special
      appearance may occur in particular types. Hurler syndrome is the prototype of
      MPS. The main findings were as follows: "J" shaped sella turcica, paddle-like
      ribs, anterior inferior beaking (hook-like) of lower thoracic-upper lumbar
      hypoplastic vertebral bodies, flared iliac wings, constrictive iliac bodies,
      diaphyseal expansion of long bones, distal ulna and radius tilt toward each
      other, bullet-like proximal phalanges and central pointing of proximal
      metacarpals. Hunter and Sanfilippo syndromes had the appearance of moderate to
      mild dysostosis multiplex. Morquio syndrome had distinctive bony changes as
      vertebral plana and tongue-like protrusion in the anterior part of the lower
      thoracic-upper lumbar vertebral bodies, particularly short of the distal deformed
      ulna and poor ossification of the proximal lateral tibial epiphyses. Although
      clinical presentations and the hallmarks of bony changes helped possible
      classification of MPS, definite diagnosis depends on enzyme analysis.

PMID- 8755173
TI  - Prevalence of Legionella pneumophila infection in children and its role in
      pediatric community-acquired atypical pneumonia.
AB  - The infection status of Legionella pneumophila in children and its role in
      pediatric community-acquired pneumonia were investigated. Because exposure to
      Legionella pneumophila may be highly variable and there has been no unanimously
      agreed-upon cut-off values in previous seroprevalence studies, 60 serum samples
      collected from infants aged 12 to 18 months were examined using
      immunofluorescence antibody test to determine the cut-off titer which represents
      past Legionella pneumophila infection. An IFA titer of greater than or equal to
      32 was found to be suitable to represent past L. pneumophila infection. A
      seroepidemiological study of the prevalence of L. pneumophila in 180 children
      showed the prevalences in children aged 7 to 18 years to be between 28.4 and 35%.
      Fifty-three paired sera were tested to determine the role of Legionella
      pneumophila in pediatric, community-acquired, atypical pneumonia. The frequency
      of confirmed disease was 0% and of presumptive cases was 5.7%. Legionella
      pneumophila was not a common etiologic agent of pediatric pneumonia in Taiwan.

PMID- 8755174
TI  - Evaluation of chronic atelectasis in children using chest computed tomography and
      bronchoscopy.
AB  - A heterogeneous group of 11 children with atelectasis persisting longer than one
      month were investigated for the causes using chest computed tomography and
      fiberoptic bronchoscope. Four young infants had right upper lobe (RUL) posterior
      segmental atelectasis simulating RUL lobar collapse in plain chest films; all had
      only two visible segmental bronchi by bronchoscopic examination. Intraluminal
      obstruction in the central airway was not a common cause of pediatric chronic
      atelectasis in this small series of patients. Only one obstructive atelectasis
      caused by dilated pulmonary arteries was detected in this study. Two patients
      with pre-existing neuromuscular diseases showed multiple atelectasis. The
      atelectatic lobes do not spontaneously re-inflate following flexible
      bronchoscopy. Investigations involving a larger number of cases are needed to
      substantiate the etiologies and to guide specific therapy for those children with
      chronic atelectasis.

PMID- 8755175
TI  - Acute disseminated encephalomyelitis in children: clinical, neuroimaging and
      neurophysiologic studies.
AB  - Nine patients below 20 years of age (4 males and 5 females), who were diagnosed
      to have acute disseminated encephalomyelitis (ADEM) by clinical findings and
      magnetic resonance imaging (MRI), were reviewed retrospectively. They ranged from
      4 months to 20 years of age with an average of 8.6 years. Seven patients (78%)
      received neurophysiological studies, which included electroencephalography,
      multimodality evoked potentials (EPs), nerve conduction velocity and/or F-wave
      measurement. The presentation symptoms were mainly headache, vomiting,
      consciousness change and motor deficits. Seven (78%) of nine patients had
      symptoms preceded by fever or upper respiratory tract infections; one (11%) was
      preceded by trivalent mumps, measles, rubella vaccination and no definite
      predisposing factor was found in another. Computed tomography (CT) scans were
      abnormal in five (71 %) of seven children, while MRI showed multiple lesions in
      seven (78%) of nine children. The lesions in MRI were mainly in the brainstem (n
      = 6), basal ganglion (n = 5), thalamus (n = 4), periventricular white matter (n =
      4) and cerebellum (n = 4). EPs disclosed spinal cord involvement in all patients
      who received the examination. Peripheral neuropathy was disclosed in one patient.
      It was concluded that associated radiculoneuropathy is possible in patients with
      ADEM. Both MRI and neurophysiologic studies are complementary for diagnosis of
      ADEM.

PMID- 8755176
TI  - Rotavirus gastroenteritis associated with afebrile seizure in childhood.
AB  - From September 1994 to April 1995, we encountered eight children, two boys and
      six girls, (aged 1 year 6 months to 9 years), presented with acute diarrhea
      followed by afebrile, generalized tonic-clonic seizures, or transient loss of
      consciousness with urine incontinence. Their biochemical data, including serum
      electrolyte levels, were within normal limits. The infective agent causing
      diarrhea was later proved by stool examination to be rotavirus, judged to be
      serotype G1 by reverse transcription - polymerase chain reaction (RT-PCR) typing.
      Cerebrospinal fluid (CSF) examinations performed in seven of the eight patients
      were within normal limits, and cultures for bacteria and virus were negative. The
      electroencephalograms (EEGs) performed from 1 to 13 days after seizure showed
      abnormal in six, and normal in two, patients. Follow-up EEGs, performed from 4 to
      11 months after onset of seizure, were all normal. None had seizure recurrence
      despite the fact that no long-term anticonvulsant had been given. From
      observation here, the authors emphasize that there is a close relationship
      between rotavirus and afebrile seizure, and the course of afebrile seizure
      following rotavirus gastroenteritis is usually benign. Further studies are needed
      to elucidate the underlying pathogenesis.

PMID- 8755177
TI  - Typhlitis in acute childhood leukemia.
AB  - Typhlitis is a necrotizing inflammation of the cecum usually found in acute
      leukemia patients on chemotherapy in the setting of agranulocytosis. We describe
      five cases of typhlitis, characterized by fever, abdominal pain, abdominal
      tenderness and watery diarrhea, occurring during periods of neutropenia. In 4
      cases, sonography showed thickening of the cecum wall. Ultrasound appears to
      offer an easy noninvasive method of diagnosing this potential lethal disease.
      Four patients were treated successfully with broad-spectrum antibiotics and bowel
      rest. There was 1 death resulting from septic complication.

PMID- 8755178
TI  - Long-term survival after neonatal arterial switch operation.
AB  - An arterial switch operation was used only for a hyperdynamic transposition of
      the great arteries beyond the neonatal period at this hospital until the end of
      1989. A 20-day-old baby girl underwent an arterial switch operation on March 3
      1992 under the impression of simple transposition of the great arteries. The
      coronary artery pattern was Shaher's type 4. An autologous aortic flap just above
      the facing commissure was used to augment the medially based trapdoor for the
      left circumflex scallop. The baby survived the operation and has been faring well
      for the past three years. This case is the longest survival after a neonatal
      arterial switch operation in our hospital.

PMID- 8755179
TI  - Holoprosencephaly: a case presenting with adipsic hypernatremia.
AB  - An 11-month-old female infant presented with mild fever, hypernatremia,
      microcephaly, and growth and developmental delay. No sign of thirst was noted in
      this infant even when the osmolality was over 318 mOsm/kg. Magnetic resonance
      imaging demonstrated a lobar type holoprosencephaly. Plasma osmolality levels
      returned to normal after forced hydration and administration of a vasopressin
      analogue. These findings suggested holoprosencephaly may be associated with a
      defect in the hypothalamic osmoreceptors that control thirst and vasopressin
      secretion.

PMID- 8755180
TI  - Tracheal agenesis: report of one case.
AB  - In this report, we present a newborn male infant with tracheal agenesis. At birth
      the term baby was cyanotic, bradycardic, and had a failure to cry. His Apgar
      scores were 3 and 3 at 1 and 5 minutes after birth. Immediately after birth, an
      endotracheal intubation was unsuccessfully attempted; however, a chest excursion
      was visible with intubation through the esophagus. Tracheal agenesis with
      esophago-tracheal fistula was highly suspected. Direct endoscopy and emergency
      computed tomography were performed and revealed tracheal agenesis. The baby died
      on day 6, and an autopsy confirmed the diagnosis. Tracheal agenesis (TA) is a
      rare cause of respiratory distress in the newborn. Cyanosis at birth, difficulty
      to perform an endotracheal intubation and a failure to cry are the
      characteristics of TA. Although continuous mechanical support through the
      esophagus can maintain vital functions, there are no effective medical or
      surgical method to correct the congenital abnormality currently. The longest
      survivor of all of the infants with TA had no more than 6 wks of live. In a
      review of the current literature, only a few cases have had the diagnosis
      established antemortem. We report a case of tracheal agenesis diagnosed by
      emergency computed tomography(CT). The role of CT in establishing this diagnosis
      has been very useful.

PMID- 8755182
TI  - [Opposable medical references in angiology].

PMID- 8755181
TI  - Intradural extramedullary epidermoid cyst of the spinal canal: report of one
      case.
AB  - A 9-year-old girl developed a progressive unsteady gait for one month.
      Hyperactive reflexes of the four extremities and a spasticity of the lower
      extremities were found. Bilateral Babinski responses were elicited. An intradural
      extramedullary mass of upper thoracic spinal cord was demonstrated using magnetic
      resonance imaging and was confirmed as an intradural extramedullary epidermoid
      cyst at surgery. This epidermoid cyst was from congenital origin. No congenital
      anomalies such as spina bifida or dermal sinus were associated. The epidemiology,
      clinical features, radiology, surgical treatment and pathology of this benign
      tumor are discussed.

PMID- 8755184
TI  - [Echo-Doppler and stenosis of the renal arteries. Report of 86 cases].
AB  - Duplex-scan is widely used for arterial stenosis diagnosis. Its role in detection
      of renal artery stenosis remains controversial (2, 17, 19, 28). The aim of this
      study was to determine retrospectively if duplex-scan is accurate for diagnosis
      of renal artery stenosis. During 36 months, 764 patients had a renal artery
      examination with duplex-scan: 90 patients had also renal arteriography. Duplex
      scan was feasible in 95% of cases (excess bowel gas or major obesity gave to
      duplex-scan incomplete results in four patients upon 90). Ninety-three per cent
      of patients had hypertension; 20% had renal failure; 61% had obstruction of
      coronary, carotid artery or lower limb arteries. Nineteen patients among 86 had
      also an intravenous renal arteriography. We compared duplex-scan with venous
      angiography and intra-arterial arteriography. Duplex-scan criteria for stenoses
      were: a maximal systolic velocity (MSV) above 180 cm/s for detection of 60% to
      79% stenoses and a MSV superior to 300 cm/s for detection of 80% to 99% stenoses.
      Global results showed a good sensitivity 59/64 (92%) and specificity 112/117
      (96%) for duplex-scan. Duplex-scan is accurate for diagnosis of renal artery
      stenosis in a selected population.

PMID- 8755183
TI  - [Aortic aneurysms due to Yersinia enterocolitica: three new cases and a review of
      the literature].
AB  - We report three cases of mycotic aortic aneurysms due to Yersinia enterocolitica.
      In all cases, serogroups are O:9. The three patients more than 70 year-old men
      with immunodeficiency underlying conditions allowing bacterial graft (neoplasia,
      diabetes mellitus, dysimmunitary syndrome, hematologic diseases). The six cases
      of the literature were clinically, biologically and epidemiologically similar.
      The strains of Y enterocolitica responsible for septicemia are especially
      serogroups O:9. This is probably due to particular virulence factors in this
      serogroup (phagocytosis resistance gene: yopH, ypkA et yop E) (yop: Yersinia
      outer membrane proteins). The presence of a pYV plasmid (plasmid yersinia
      virulence), found in Yersinia pathogen strains, lead to bacterial proliferation
      in the tissues. The authors discuss pathophysiological mechanisms involved in
      arterial bacterial graft following an Y. enterocolitica infection.

PMID- 8755185
TI  - [Erythermalgia: an enigma].

PMID- 8755186
TI  - [Classification of erythermalgia].
AB  - Several classifications have been proposed for erythermalgia according to
      causality (primary or secondary) or age of onset (presuming that all early-onset
      are primary). Recently a classification in three types of erythromelalgia have
      been proposed. Erythromelalgia and erythermalgia are defined as two independent
      and completely different disease entities. Clinically there are three different
      types of recurrent red, warm and burning pain in the extremities. That need to be
      distinguished for effective treatment according to their etiology:
      erythromelalgia in thrombocythaemia, primary erythermalgia and secondary
      erythermalgia. We recently observed 19 cases of erythermalgia; nine had primary
      erythermalgia; in 6 of 9, symptoms were relieved with aspirin. Ten of them had a
      secondary erythermalgia: 5 due to myeloproliferative disorders (erythromelalgia),
      2 systemic lupus erythematosus and 3 to drugs. We used a two-level classification
      with a first level of primary or secondary erythermalgia, and a second level for
      primary erythermalgia, of familial or nonfamilial primary and for secondary
      erythermalgia, of thrombocythaemia disorders or other.

PMID- 8755187
TI  - [False erythermalgia].
AB  - The differential diagnosis of erythermalgia is sometimes complicated by the
      absence of consensus on proposed diagnostic criteria. Unwarranted diagnosis can
      result from any clinical situation leading to burning sensations in the limbs.
      This can occurs in patients with peripheral neuropathies who often experience
      dysesthesia when going to bed when the legs are under the covers; in such cases,
      redness and local warmth are missing. Venous insufficiency can also produce
      sensations of warm feet, often at retiring, together with edema and an increase
      in local heat. Algodystrophy, during the inflammatory phase can also mimic
      erythermalgia with intense pain and local modifications. Nevertheless, the
      unilateral aspect and persistence of the symptoms together with the post
      traumatic situation usually directs the diagnosis. Acrodynia is a rare disease
      caused by excessive mercury intake and should be discussed in children. Vasomotor
      impairment in the limbs is the main sign. The red color of the hands and feet is
      accompanied by intense paroxysmal burn-type pain. The diagnosis is confirmed by
      high mercury levels in urine. Fabry's disease is a hereditary sphingolipidosis
      transmitted on chromosome X and occurs predominantly in men, often starting early
      in childhood with burning sensation in the limbs. The diagnosis should be
      entertained in children with pseudo-erythermalgia and is confirmed by
      chromatographic search for abnormal sphingolipids in the urine.

PMID- 8755188
TI  - [Erythermalgia and systemic lupus erythematosus].
AB  - We report three cases of erythermalgia associated with systemic lupus
      erythematosus corresponding to different clinical situations in such an
      association. The first patient developed erythermalgia during the course of
      systemic lupus erythematosus. In the second, erythermalgia preceded other
      symptoms of systemic lupus erythematosus by four years. In the third,
      erythromelalgia was not related to a flare-up of systemic lupus erythematosus,
      but to thrombocythemia, a complication of immunosuppressive therapy. These cases
      permit a discussion on terminology and classification of erythromelalgia and
      erythermalgia. However, more than terminology or classification into three types
      or into adult-onset and early-onset (childhood) erythromelalgia, the important is
      to consider primary and secondary forms. We used a classification into two types:
      primary (or erythermalgia) with subdivision into sporadic and familial subtypes,
      and secondary with subdivision into erythermalgia related to myeloproliferative
      disorders and erythermalgia related to other diseases, such as systemic lupus
      erythematosus, or to drugs (erythermalgia-like syndrome).

PMID- 8755189
TI  - [Carotid dissection during childbirth].
AB  - A 33-year-old woman presented transient ischemic attach (hemiparesis of the left
      arm and right amaurosis), 14 days after childbirth, due to dissection of the
      right carotid that occurred probably during delivery as suggested by right
      earache at that time. Carotid dissection during pregnancy or after childbirth is
      rare an exceptional during delivery. Neurological symptoms and arterial lesions
      were followed by duplex ultrasound.

PMID- 8755190
TI  - [Dissecting aneurysm of the external iliac artery. An unusual course of
      endofibrosis in an athlete].
AB  - A 42-year-old man was consulted because of a pain in his left leg. He was a
      highly trained biker since 20 years. The echo-Doppler and arteriography evidenced
      a stenosis, probably due to endofibrosis of the external iliac artery. In
      addition, it showed an aneurysm and an intimal dissection of this artery. The
      arteriography confirmed this diagnosis, and normal aspect of the other arteries.
      Neither conservative nor endovascular treatments were possible because of the
      anatomic lesions. We resected the external iliac artery and performed a by-pass
      with the great saphenous. The result at the 5th month was clinically good. The
      echo-Doppler control did not show any abnormality. The natural course of the
      endofibrosis of athletes is unknown, although stenosis, revealed by intermittent
      claudication is usually observed. Only a few cases of dissection and no
      aneurysmal degeneration have been described before.

PMID- 8755191
TI  - [Early detection of atherosclerosis].
AB  - Within certain limits, it is not possible to screen for asymptomatic early
      atherosclerotic lesions with the aim of prevention. The effectiveness of
      different screening tests varies. A vascular murmur has little predictive value.
      Coronary or aorto-iliofemoral calcifications sometimes occur early. ECG or
      exertion thallium scan and low distal pressure at rest or during exercise can
      provide indirect clues as can continuous Doppler or the carotids or peripheral
      vessels. Pulsed Doppler and color-Doppler are the best screening tools for
      detecting wall thickening or a silent plaque. Arteriography is essential for
      patients with coronary artery disease and is often required for carotid or
      abdominal vessels, but is unfortunately an invasive method and underestimates
      lesions which do not give a defect image. Angioscopy and endoechography are
      difficult to manipulate and interpret and cannot be used in routine screening. No
      biological or genetic markers have been identified as formal indicators of
      atherosclerosis. Screening is justified in young patients at risk (high blood
      pressure, intensive smoking, major hyperlipidemia, diabetes, severe family
      history) because early lesions would lead to a more adapted treatment which can
      be expected to stabilize or even improve early lesions, or even reduce the risk
      of plaque rupture. In addition, carotid or iliofemoral lesions increase the risk
      of coronary artery disease.

PMID- 8755192
TI  - [Thrombo-aspiration: a simple technique].

PMID- 8755193
TI  - [Endovascular recanalization of primary thromboses of the iliac artery].

PMID- 8755194
TI  - [Importance of determining troponin I after coronarography].

PMID- 8755195
TI  - Antiproliferative effect of basic fibroblast growth factor-saporin mitotoxin on
      keratocytes in culture.
AB  - We evaluated the effect of the conjugate of basic fibroblast growth factor (FGF2)
      and saporin (FGF2-SAP) on proliferation of cultured keratocytes. Cultured rabbit
      and human keratocytes were incubated in medium containing 0.01 to 100 nM of
      chemical conjugate of EGF2 conjugated by disulfide bond to saporin (CCFS1), FGF2
      genetically fused to saporin (rFGF2-SAP), FGF2, or saporin for three hours or
      four days and cell proliferation was quantified four days after the drug
      treatment. Proliferation of rabbit and human keratocytes was effectively
      inhibited by three hour and by four day exposure to CCFS1 and rFGF2-SAP in a dose
      dependent manner, whereas it was affected minimally by four day exposure to
      saporin. Their inhibitory effects were detected at concentrations above 0.1 or 1
      nM, and were most prominent in serum-stimulated rabbit keratocytes. These results
      suggest a potential role for FGF2-SAP in limiting proliferation of keratocytes
      during corneal wound healing.

PMID- 8755196
TI  - Efficacy of ciprofloxacin and dexamethasone in experimental pseudomonas
      endophthalmitis.
AB  - To determine injection time and effective dose of ciprofloxacin in
      endophthalmitis and to evaluate the effectiveness of dexamethasone. In rabbits,
      Pseudomonas aeruginosa (2 x 10(4) CFU/0.1 ml) was inoculated intravitreally. At
      6, 12, 18, 24 hours postinoculation, single intravitreal doses of ciprofloxacin
      (300 micrograms/0.15 ml or 100 micrograms/0.05 ml) alone or with dexamethasone
      (400 micrograms) were given. Electrophysiological and histologic measures were
      utilized to rate drug effectiveness. 300 micrograms ciprofloxacin was effective
      in killing P. aeruginosa at 6 and 12 hours postinoculation, but one hundred ug
      ciprofloxacin was not effective. 300 ug ciprofloxacin had no significant effect
      in killing P. aeruginosa at 18 hrs and 24 hrs postinoculation. Eyes treated with
      dexamethasone (400 micrograms) and ciprofloxacin (300 micrograms) at 6 hours
      postinoculation did not differ from eyes treated with ciprofloxacin alone.
      Cultures from eyes treated with dexamethasone and ciprofloxacin at 12 hours
      postinoculation were positive. Cultures from eyes treated with ciprofloxacin
      alone were negative. The failure of treatment at 18 hrs and 24 hrs
      postinoculation may be due to either an increased rate of clearance of drugs from
      the eyes or a reduced bactericidal effect of ciprofloxacin which could be altered
      by acidic pH, degree of hypoxia or bacterial counts. Dexamethasone had no
      beneficial effect in the treatment of P. aeruginosa endophthalmitis in the early
      phase.

PMID- 8755197
TI  - Increased numbers of Langerhans cell and expression of HLA-Dr antigen in the
      giant papilla of patients with giant papillary conjunctivitis.
AB  - A study of histopathologic changes, ultrastructure, and expression of the HLA-Dr
      antigen within the giant papillae of patients with giant papillary conjunctivitis
      was performed to determine whether cell-mediated immune response is related to
      this condition. Conjunctival giant papillae from ten patients with giant
      papillary conjunctivitis were examined by light and electron microscopy and by
      the indirect immunofluorescent staining method with HLA-Dr antibody. The
      infiltration of eosinophilic neutrophils and granules was most prominent, with
      the occasional infiltration of mast cells, as shown by light microscopy. The
      infiltration of activated fibroblasts and Langerhans cells was also observed.
      Cells expressing HLA-Dr antigen were also markedly increased, as shown by the
      immunofluorescent method. These findings suggest that delayed hypersensitivity
      may, along with the processes of antigen presentation by HLA-Dr-expressing
      (including Langerhans) cells, contribute to the pathogenesis of giant papillary
      conjunctivitis.

PMID- 8755198
TI  - Relationship between optic nerve head parameters of Heidelberg Retina Tomograph
      and visual field defects in primary open-angle glaucoma.
AB  - To investigate the correlation between optic nerve head configuration and visual
      field defects, optic nerve head analysis using confocal scanning laser tomography
      (Heidelberg Retina Tomograph, HRT) and automated static threshold perimetry using
      a Humphrey Field Analyzer (program C30-2) were performed on 81 eyes of 44 primary
      open-angle glaucoma (POAG) patients. The optic nerve head parameters-rim area,
      rim volume, mean retinal nerve fiber layer thickness, height variation contour,
      and third moment in contour were measured by HRT and were analyzed for
      correlation with visual field indices-mean deviation, and corrected pattern
      standard deviation. All optic nerve head parameters except HVC correlated
      significantly with the visual field indices; the highest correlation was between
      rim area and mean deviation (r = 0.6172, p < 0.00001). The rim area of the
      superior and inferior quadrants correlated significantly with the visual field
      defects in corresponding sectors. Structural optic disc measurements by HRT
      correlated significantly with functional optic nerve head damage in POAG.

PMID- 8755199
TI  - Effect of seasons upon intraocular pressure in healthy population of China.
AB  - Studies have been shown that intraocular pressure (IOP) shows a seasonal
      variation, but amount of change differs from study to study. The variability in
      their results may be due to negligence of factors that can affect IOP. Due to
      differences in environmental conditions of China than other countries, we
      investigated seasonal variations in IOP of 103 healthy male Chinese of Shanghai.
      IOP was measured each month over the course of fourteen months with the Goldmann
      applanation tonometer. The average intraocular pressures in the winter months
      were higher than those in the spring, summer, and autumn months. The IOP
      difference between winter and summer months was found to be 1.4 +/- 0.7 mmHg.
      This study confirms that season influences IOP. As compared to other nations,
      effect of seasons on IOP seems to be somewhat less pronounced in Chinese. The
      possible mechanisms, responsible for the seasonal variation of intraocular
      pressure, are also postulated.

PMID- 8755200
TI  - Effects of postoperative mitomycin C eyedrop on trabeculectomy in refractory
      glaucoma patients.
AB  - To investigate the effects of postoperative mitomycin C (MMC) eyedrop as an
      adjunct to intraoperative MMC in refractory glaucomas, 15 eyes of 14 glaucoma
      patients (age; 47.0 +/- 15.5 years) in need of trabeculectomy were studied.
      Preoperative diagnoses were secondary glaucoma to uveitis in seven patients,
      neovascular glaucoma in four, pseudophakic glaucoma in three, and aphakic
      glaucoma in one. Six patients who had neovascular glaucoma or history of a failed
      trabeculectomy with intraoperative 0.2 mg/ml MMC received intraoperative 0.4
      mg/ml MMC. The others received 0.2 mg/ml MMC for 3 minutes. During the follow-up
      period, postoperative MMC eyedrop was applied, depending on the condition of the
      filtration bleb. The eyedrop was 0.2 or 0.4 mg/ml, applied four times a day for
      one week. The follow-up period was 18.1 /+- 7.4 months. The success rates were
      93.3%, 86.7%, and 78.0% at postoperative 1, 4, and 18 months, respectively. There
      was neither early hypotony nor wound leak. Corneal epithelial defects (26.7%),
      corneal ulcers (6.7%), and cataracts (6.7%) were, however, observed.
      Postoperative MMC eyedrop application was a convenient and effective adjunct to
      intraoperative MMC in refractory glaucomas.

PMID- 8755201
TI  - The effect of low-and high-dose adjunctive mitomycin C in trabeculectomy.
AB  - To compare the effects of three different concentrations of mitomycin C (MMC) as
      an adjunct therapy to trabeculectomy, we reviewed 26 patients (36 eyes) who
      underwent trabeculectomy in which MMC was applied intraoperatively. The time of
      application was 5 minutes, and the concentration of MMC was 0.1 mg/ml (n = 10),
      0.2 mg/ml (n = 17) and 0.4 mg/ml (n = 9), respectively. Complete success was
      defined by intraocular pressure (IOP) of 21 mmHg or less without medication at
      postoperative 3 months. There was no statistical difference among the three
      groups in mean age of patients, preoperative IOPs, and the numbers of
      premedication. The mean IOP at postoperative 3 months was significantly lower in
      the 0.4 mg/ml group (10.4 +/- 5.5 mmHg) than in the 0.2 mg/ml group (16.1 +/- 4.7
      mmHg) (p < 0.05). The complete success rate in the 0.4 mg/ml group was 100%,
      which was significantly higher than the rate of 40% obtained with the 0.1 mg/ml
      group (p < 0.05), but was not significantly different to the rate of 70.6% in the
      0.2 mg/ml group (p > 0.05). There was no statistical difference among the three
      groups in the success rate regardless of medication, and the size and longevity
      of the filtering bleb. Postoperative hypotony was noted in two eyes of the 0.4
      mg/ml group.

PMID- 8755202
TI  - Preservation of retinal sensitivity in central visual field after panretinal
      photocoagulation in diabetics.
AB  - Changes in retinal sensitivity within central 30 degrees following panretinal
      photocoagulation (PRP) for more severe diabetic retinopathy were investigated.
      Twenty-five eyes with visual acuity of 0.4 or better and minimal maculopathy were
      studied prospectively. All underwent PRP in two sittings, and Humphrey field
      analyzer 30-2 threshold test was done before and 1 week, 1 and 3 months after the
      treatment. The mean retinal sensitivity threshold was obtained from each
      hemifield between 15 and 30 degrees and from the central 15 degree area, and the
      changes in the values were analyzed. Mean sensitivity threshold in the upper
      visual field at pre-PRP, post-PRP 1 week, 1, 3 months were 15.62, 13.81, 14.31,
      14.85, respectively. Values in the lower field were 18.71, 17.25, 17.10, 18.17.
      Difference between pre-PRP and post-PRP was statistically significant at 1 week
      but no longer thereafter. Retinal sensitivity within the central 15 degrees
      remained stable. The data show that retinal sensitivity decreases significantly 1
      week after PRP but recovers upto 95% of pre-PRP level over the following 3
      months.

PMID- 8755203
TI  - Intravitreal cysticercosis.
AB  - Examination of a 36-year-old man with naked visual acuity of 20/20 revealed a
      floating, conspicuous cyst of Cysticercus cellulosae in the vitreous cavity of
      the right eye. A vitreous traction band from the vitreous base and the optic disc
      was connected to the lodging bulb of the cyst. In the superonasal area, an ovoid
      retinal break surrounded by a white retinal lesion with two elliptical retinal
      hemorrhages was found, and this seems to be the previous lodging site of the
      cyst. A pars plana vitrectomy was performed to remove the parasite, and laser
      photocoagulation was carried out around the retinal break. Four months after the
      operation, the patient was satisfied with naked visual acuity of 25/20 without
      any complication in the affected eye.

PMID- 8755205
TI  - [New cytogenetic techniques in hematologic diagnosis].

PMID- 8755204
TI  - Hematic cyst formation after repair of blow-out fracture.
AB  - Alloplastic implants are known to be inert for many years, though complications
      are infrequently reported many years after their insertion. We report the case of
      a patient who had undergone a blow-out fracture repair five years before the
      discovery of a hematic cyst. He had been free of symptoms for the first five
      years after his orbital floor repair but then developed pain on eyeball movement
      and persistent vertical diplopia, which finally led to surgical intervention. At
      surgery, a hematic cyst was found to have formed around the implanted silastic
      plate. When alloplastic material is used in orbital fracture repair, we should be
      alert for late complications which may occur many years after surgery.

PMID- 8755206
TI  - [Detection of the PML/RAR alpha rearrangement in acute promyelocytic leukemia
      using a reverse PCR method].
AB  - AIMS: This study describes a molecular method of reverse transcription polymerase
      chain reaction (RT-PCR) to detect the rearrangement PML/RAR alpha in acute
      promyelocytic leukaemia (APL) in order to assess its specificity and sensibility,
      and to evaluate its utility in the characterization of APL patients. PATIENTS AND
      METHODS: Between January and June of 1995, 64 samples of bone marrow and
      peripheral blood stem cells (PBSC) cytapheresis were studied. There were 58 APL
      samples (23 patients: 10 samples obtained with disease activity, 43 samples in
      complete remission (CR) and 5 PBSC samples) and 6 control samples, of non-APL
      hematological neoplasms (3 other AML, 1 CML, 1 ALL, and 1 MDS). On the RNA
      obtained from the isolated mononuclear cells of each sample a conserved region of
      the PML/RAR alpha fusion gene was amplified by using a RT-PCR with specific
      primers. RESULTS: The sensitivity assays were performed by diluting PML/RAR alpha
      positive RNA samples into RNA of controls. The RT-PCR assay was capable to detect
      the PML/RAR alpha until an 1/1000 dilution in negative control RNA. Nine out of
      58 APL samples failed in the amplification of the control gene, and were
      considered non-evaluable. None of the 6 control samples showed PML/RAR alpha
      rearrangement. Nine out of 10 APL samples with disease activity were positive for
      the presence of PML/RAR alpha (the non-positive sample was a non-evaluable one).
      Six out of 43 APL samples in CR showed the rearrangement, 3 of them corresponding
      to 2 patients who posteriory relapsed 12 and 19 months after 1st CR. The other 3
      positive samples came from other 3 APL patients (24 months in 3rd CR, 14 months
      in 1st CR and early CR), who remained in CR at the end of the study. No relapse
      could be noted in patients with negative PCR samples. PML/RAR alpha was not found
      in any of the 5 APL PBSC samples studied. CONCLUSIONS: The RT-PCR method
      described here seems to be highly specific as it only detects this rearrangement
      in LPA patients. Furthermore, the presence of PML/RAR alpha in CR patients could
      be related to relapse. For all these reasons, this molecular method shows great
      usefulness and can be advocated, not only for assessing diagnosis, but for as
      monitoring minimal residual disease in the post remission follow up.

PMID- 8755207
TI  - [Iron intake and pharmacologic supplements in medium and long-distance runners].
AB  - PURPOSE: To assess in a group of female runners the iron uptake and
      pharmacological supplementation, plus the variation induced in haematological
      values and iron deposits. MATERIAL AND METHODS: The total and haeme Fe uptake as
      well as the blood parameters were studied in a group of 25 female median and long
      distance runners and in a control group comprised of 82 women with no sport
      activities. Eleven of the runners had usually been on pharmacologic iron
      supplementation. All of the subjects completed a diet regimen for 7 days
      controlled by means of food weighing. RESULTS: Total Fe ingestion was
      significantly higher in the runners (13.6 mg/day) than in the control group (11.3
      mg/day (p < 0.01), although the minimum established by the Diet Recommendations
      was reached by neither group. The ingestion of haeme-Fe was higher in non
      supplemented runners (1.64 mg/day) with regard to those on iron supplementation
      (1.39 mg/day) and the women of the control group (1.34 mg/day). Serum ferritin
      levels were also higher in non-supplemented runners (38.1 ng/mL), with lowest
      values in the runners receiving iron supplement (29.7 ng/mL). CONCLUSIONS: Serum
      ferritin levels in female runners appear to be related with the ingestion of
      haeme-Fe rather than with total iron ingestion. On the other hand, the
      pharmacologic iron supplementation given here appears inadequate for most of the
      runners studied.

PMID- 8755208
TI  - [Cytogenetic study of 121 patients suffering from various hematologic neoplasms
      using the in situ hybridization technique].
AB  - PURPOSE: In situ hybridization (ISH) is an efficient tool for detecting
      chromosomal abnormalities in haemopoietic malignancies. Structural and numerical
      changes typical of most pathological entities can be detected using chromosome
      specific probes on interphase or metaphase cells by means of this technique.
      PATIENTS AND METHODS: In this report we present chromosome analysis combining
      conventional cytogenetics with ISH in 121 patients affected with different
      haematological diseases. We have studied 92 patients with B-chronic
      lymphoproliferative disorders (B-CLPD), 11 myelodysplastic syndromes (MDS), 17
      acute nonlymphocytic leukaemias (ANLL), 1 acute lymphocytic leukaemia and 1
      aplastic anaemia. The ISH was carried out with two kind of biotin-labeled probes:
      a) 8 and 12 centromeric alpha satellite probes and b) whole painting chromosome
      (WPC) library probes from all the chromosomes except numbers 10, 16, 21, X and Y.
      RESULTS: The cytogenetic analysis of B-CLPD has been hampered by several
      problems. These leukaemic cells have very low spontaneous mitotic activity and
      the cell response to mitogens is often poor, unpredictable and variable. Even so,
      an extra chromosome 12 (+ 12) is one of the most frequent abnormal karyotypes
      reported. ISH and chromosome 12 specific biotinylated alpha satellite DNA probe
      was applied in 84 patients with B-CLPD. Among 50 patients with typical chronic
      lymphocytic leukaemia (CLL) the ISH studies showed two signals of hybridization
      in the 50 cases. By conventional cytogenetics 9 out of 18 atypical CLL showed
      chromosomal abnormalities and 7 of them trisomy 12. ISH detected trisomy 12 in 11
      of these cases. Trisomy 8 is the most frequent karyotypic change in MDS and ANLL.
      Cytogenetic results revealed a clear extra copy of chromosome 8 in 13 cases. In
      all of these trisomic cases, the presence of trisomy 8 clone was confirmed by
      ISH. ISH revealed trisomy 8 not detected by conventional cytogenetics in 7 cases.
      The yield of trisomy is much higher with the ISH technique than with conventional
      cytogenetics. Finally, conventional cytogenetics combined with CISS (chromosomal
      in situ suppression) hybridization was performed in 15 patients affected with
      different haematological diseases showing structural aberrations, complex
      karyotypes or marker chromosomes. CONCLUSIONS: Our results show that ISH can
      detect both numerical and structural chromosome changes with high specificity and
      reliability. The fact that chromosome spreads of very poor quality can now be
      included in such analysis is the decisive advantage of this approach.

PMID- 8755209
TI  - [Organizational models for the hematology areas of the district hospitals of
      Catalonia].
AB  - PURPOSE: The haematological assistance in Catalonia is based upon the district
      hospitals, in the first step, and the stage III hospitals located usually in
      higher population nuclei, in the second step. The purpose of this work was to
      analyse the resources of the "primary haematological assistance" network provided
      by the district hospitals, to evaluate them and to propose a model for their
      organisation. MATERIAL AND METHODS: An enquiry was carried out to all members of
      the Grup de Treball d'Hospitals Comarcals de Catalunya (Catalonia's District
      Hospitals Task Force). The evaluable data included demographic figures of the
      population assisted, personnel of each haematological area, organising structure,
      clinical activity, cytomorphology, blood banks, laboratories and continuous
      formation activities. RESULTS: The enquiry was answered by 15 of the 21 district
      hospitals (71.4%) with haematologists in Catalonia. The population assisted in
      those hospitals is 2,100,000 (ranging between 55,000 an 450,000). All centres are
      integrated in the National Health network. Eleven of the hospitals analysed have
      only one haematologist (73.3%). If his dedication is 100% of the time, this would
      represent a doctor for 105,000 people. The time devoted to work is 690 hours a
      week for all the population, with a mean of 3,043. Four patients assisted per
      hour. The total number of hospital beds is 3,353 (50-450), with a mean number of
      1 haematologist for every 167.6 beds. The number of patients hospitalized due to
      blood diseases ranges between 3 and 13 per month. Six of the 15 centres are
      adjunct to the outpatient clinic. Two centres have a blood bank and 7 have
      developed an autotransfusion programme. All the centres but one perform oral
      anticoagulant treatment follow-up, the number of patients assisted ranging from
      20 to 210 per week. None of the hospitals has a separate Haematology Service; in
      most of them haematology is structurally and functionally dependent from
      Laboratories and in some there is a mixed Laboratory/Internal Medicine functional
      organisation, depending of the Medical Direction. No haematologist is ever on
      call specifically for his specialty. Continuous formation activities are carried
      out in 9 of the 15 centres (60%). COMMENT: Several measures are proposed to
      improve the haematological assistance, acting on different levels: continuous
      formation, patient flows and circuits, resident doctors training, anticoagulant
      treatment network, organisation models, credit cards from the Spanish Association
      of Haematology.

PMID- 8755210
TI  - [Bone marrow in human immunodeficiency virus (HIV) infection: the bone marrow in
      the etiopathogenesis of the hematological changes associated with HIV infection].

PMID- 8755211
TI  - [Bone marrow in human immunodeficiency virus (HIV) infection: morphological
      changes in the bone marrow in HIV infection].

PMID- 8755212
TI  - [Pelvic Castleman's disease: apropos of a case].
AB  - Castleman's disease (CD) is a enigmatic lymphoid disease of unknown etiology
      which rarely manifest itself as an isolated pelvic mass. We report a case of
      pelvic Castleman's disease masquerading as a uterine myoma. The patient presented
      symptoms related to compression of adjacent structures, splenomegaly and
      abdominal lymphadenopathy, the laboratory data revealed positive Epstein-Barr
      virus serology, elevated beta 2-microglobulin level and presence of antinuclear
      antibodies. The intraabdominal involvement, histological patterns and clinical
      forms of this condition are reviewed. Likewise etiopathogenic, radiologic and
      therapeutic aspects related with this entity are discussed. We suggest that
      pelvic Castleman's disease should be included in the differential diagnosis of
      females presenting a pelvic mass containing calcifications.

PMID- 8755213
TI  - [Acute lymphoblastic leukemia with L1 morphology arising during treatment for ALL
      L3 in a child with AIDS].
AB  - A child with AIDS is presented who developed L1-ALL while being treated for L3
      AL. After achievement of complete remission of the former, he suffered a relapse
      with L3 morphology. Although the possibilities of a shift in both the morphology
      and the immunophenotype of ALL in relapse are well known, the rarity of L1-ALL in
      association with AIDS is stressed by the authors, along with the factors related
      with the morphologic and phenotypic changes shown by these patients.

PMID- 8755215
TI  - [Hematology Standardization Committee. Recommendations of the International
      Council for Standardization in Hematology (ICSH) for the evaluation of
      hematologic autoanalyzers].

PMID- 8755214
TI  - [Erythroblastopenia during recurrence of a thymoma associated with myasthenia
      gravis. Apropos of a new case].
AB  - A new case of thymoma, myasthenia gravis and pure red cell aplasia is presented.
      Pure red cell aplasia came out 10 years after the diagnosis of the two other
      diseases in one of several relapses of metastatic thymoma with clinical signs of
      myasthenia. Surgery, chemotherapy and radiotherapy besides pyridostigmine
      treatment were used in the clinical course of the patient. A phenotypical change
      of medullary T lymphocytes (CD4 to CD8) was observed at the same time of pure red
      cell aplasia diagnosis. A dual role of medullary CD2+ T cell lymphocytes,
      stimulant and suppressive, over erythroid progenitor cells (BFU-E and CFU-E) was
      suggested by in vitro cultures.

PMID- 8755217
TI  - [Variant hairy-cell leukemia and autoimmune hemolytic anemia].

PMID- 8755216
TI  - [The whole dose at once?].

PMID- 8755218
TI  - [Asymptomatic pathological rupture of the spleen as the presenting form of acute
      lymphoblastic leukemia].

PMID- 8755220
TI  - [Does laparoscopic treatment of abdominal infections generate bacteremias].

PMID- 8755219
TI  - Association of splenic lymphoma with villous lymphocytes and primary biliary
      cirrhosis in a man.

PMID- 8755221
TI  - [Total colectomy with ileorectal anastomosis (IRA): our experience in 57
      patients].
AB  - Total colectomy with IRA in ulcerative colitis, Crohn's disease, familial
      polyposis and multicentric colonic cancer is still debated. In this paper the
      Authors present their experience with a retrospective review of 57 patients,
      treated in the Surgical Department of Pisa's University from 1978 to 1990.
      Through the results obtained, it is concluded that total colectomy with IRA is a
      valid procedure in the treatment of multiple polyposis, but must be associated
      with a long and careful follow up using fulguration for local recurrence. The
      usefulness of this treatment in multicentric colonic cancer is confirmed.
      However, the use of IRA in ulcerative colitis is debatable. This series shows the
      failure of colectomy with IRA in patients with Crohn's disease, due to the high
      incidence of local recurrences requiring reoperation.

PMID- 8755222
TI  - [Primary torsion of the greater omentum. A case report and review of the
      literature].
AB  - The Authors report a case of acute abdominal syndrome, caused by primary torsion
      of the greater omentum. They describe the still unknown aetiopathogenetic
      factors, pointing out the problems of preoperative diagnosis.

PMID- 8755223
TI  - [Aneurysms of the external jugular vein].
AB  - External jugular vein aneurysms are rare and appear as a soft, compressible mass
      in the neck. Three cases are herein reported. Ultrasonography is the
      investigation of choice. Surgical excision is indicated, specially in case of
      giant and thrombosed venous aneurysm.

PMID- 8755224
TI  - [Surgical treatment of pancreatic pseudocysts].
AB  - The Authors report their experience of 62 consecutive patients with pancreatic
      pseudocysts observed within the period 1973-1993. Spontaneous resolution of the
      pseudocyst occurred in 16 cases. Forty-five patients were surgically treated (31
      post-necrotic cysts, 5 post-traumatic cysts and 9 retention cysts); operations
      included internal drainage in 32 (cystojejunostomy in 13, cystogastrostomy in 18
      and cystoduodenostomy in one), external drainage in 8 and pancreatic resection in
      5 patients. One patient underwent percutaneous catheter drainage of a post
      necrotic pseudocyst. Indications for surgery included complications,
      nonresolution or persistence of symptoms, and extension. The operative mortality
      and morbidity rates were higher in the patients submitted to external drainage
      (22.2% vs 6.2%; 55.5% vs 21.8% respectively). On the basis of the results the
      Authors conclude that the internal drainage, particularly cystojejunostomy,
      should be considered the operation of choice for pancreatic pseudocysts because
      of the lower mortality and morbidity. On the contrary, external drainage is
      indicated for infected or ruptured pseudocysts.

PMID- 8755225
TI  - [Perforated diverticulitis of the colon: modalities of the surgical treatment].
AB  - A retrospective study was carried on 66 patients surgically treated for
      perforated diverticular colonic disease: 22 had acute phlegmon or pericolic
      abscess and underwent primary resection and anastomosis. Of the remaining 44
      patients, who had multiple pericolic and/or pelvic abscesses, or generalized
      peritonitis, in 30 cases the Hartmann procedure was used, 6 underwent Mikulicz
      operation, while drainage with proximal colostomy was performed in 5 cases, and
      simple suture and drainage in the last 3 cases. Operative mortality was 18.2%.
      Mortality rate was higher in patients treated by colostomy and drainage. The
      Hartmann procedure and resection-anastomosis patients had a mortality rate of
      23.3% and 4.4% respectively. No mortality was registered among patients treated
      with suture and drainage.

PMID- 8755226
TI  - [Pulmonary metastasis of colorectal cancer: clinico-therapeutic considerations].

PMID- 8755227
TI  - [Cholecysto-biliary fistulas].
AB  - Out of a total of 910 cholecystectomies performed on patients suffering from
      biliary calculosis, from January 1980 to December 1994 the Authors observed two
      cases of cholecysto-biliary fistulas (0.2%), a complication which can rarely
      affect biliary stones. In the light of the international literature and of their
      own, however, limited experience, the Authors take into account the
      pathophysiologic and clinical aspects of this pathology. They agree with the
      literature data on the lack of specificity of the clinical signs and uselessness
      of preoperative diagnostic tools, the only exception sometimes being E.R.C.P. The
      Authors find Csendes' cholecysto-biliary fistulas classification extremely useful
      as far as the subsequent surgical treatment is concerned. The latter should be
      electric, i.e. evaluation of each single case depending on the type of fistula,
      its size, conditions of its edges, dilatation of the main bile duct. Surgery may
      range from a simple suture of the fistula edges with endoluminal drainage,
      associated or not to surgery of the papilla, to a biliary digestive anastomosis.

PMID- 8755228
TI  - [Leiomyosarcoma in jejunal diverticulum. A case report and review of the
      literature].
AB  - The Authors describe a case of double jejunal diverticulum, characterized by the
      presence of a leiomyosarcoma in one diverticulum and ectopic pancreatic mucosa in
      the other. The rarity of the occurrence of a leiomyosarcoma in the diverticular
      area is outlined; only few cases have been reported in Literature, excluding
      those originating, from Meckel's diverticulum. Barium X-rays of the small
      intestine allowed the neoplasia to be discovered, while an Echo-Color-Doppler
      examination suggested the histological type given the high vascularization
      typical of leiomyosarcomas.

PMID- 8755229
TI  - Acute appendicitis. How many uncorrect diagnosis? A clinical and histological
      evaluation of 124 cases treated with emergency procedure.
AB  - Acute appendicitis is a very common disease in western countries, affecting the
      entire population with higher prevalence in younger people. The diagnosis of the
      disease is still basically performed through the clinical evaluation of the
      patient, while peripheral White Cell Count or imaging techniques such as
      ultrasonography are poorly helpful. Therefore, a great number of patients is
      operated without finding a severe involvement of the appendix at intraoperative
      observation. To evaluate the rate of false acute appendicitis and to correlate
      the histological involvement with the clinical behavior of the disease the
      Authors carried a prospective study during a period of 28 months on 124 patients
      with a diagnosis of acute appendicitis treated on emergency basis.

PMID- 8755230
TI  - [The role of identification of the recurrent laryngeal nerve in thyroid surgery].
AB  - Recurrent laryngeal nerve paralysis in the most serious complication of thyroid
      surgery. Five-hundred and sixty eight-consecutive operations for benign disease
      of the thyroid were retrospectively analyzed. Bilateral identification of the
      inferior laryngeal nerve was performed in 447 cases, whereas in 121 patients the
      identification was unilateral. The rate of primary postoperative vocal cord
      paralysis was 3.7% and permanent palsy rate was 0.8%. Present results compared
      with those of Literature confirm that recurrent nerve paralysis is a less
      frequent complication when the nerve is routinely identified and correctly
      prepared.

PMID- 8755231
TI  - Minilaparotomy with rectus muscle sparing: a personal technique for
      cholecystectomy.
AB  - The present paper describes a minilaparotomy technique characterized by an
      horizontal incision of the skin and two successive vertical incisions which run
      along distinct sagittal as well frontal planes, sparing, thus, the rectus muscle.
      This approach, in comparison to other minilaparotomy techniques, ensures a
      reduced incidence of incisional hernia, decreased postoperative pain and optimal
      cosmetic results. The technique is useful when laparoscopic cholecystectomy is
      contraindicated or the laparoscopic apparatus is not available.

PMID- 8755232
TI  - [Emergency laparoscopic surgery].
AB  - The acute abdomen continues to be a large part of the general surgeon's workload.
      The continuing advances in laparoscopic surgery have already permitted many
      emergency procedures to be performed by this route. Since 1993 the Authors
      perform an explorative laparoscopy in patients with acute abdomen. Once the
      diagnosis is verified, the endoscopic view suggests to continue the intervention
      laparoscopically or to convert the procedure. 70 acute cholecystitis, 57 acute
      appendicitis, 15 perforated peptic ulcers, 6 gynaecological emergencies, 8
      intestinal occlusions and 2 splenic traumas were treated according to this
      approach. The results obtained testify that laparoscopy is a valuable diagnostic
      tool for the surgeon in case of acute abdomen and an interesting therapeutic
      alternative in selected cases. However, it requires extensive experience in
      laparoscopic techniques.

PMID- 8755233
TI  - [A comparative study of BCG and mitomycin C in superficial carcinomas of the
      bladder].

PMID- 8755234
TI  - In vitro metabolism of a potent HIV-protease inhibitor (141W94) using rat, monkey
      and human liver S9.
AB  - Compound 141W94 (Vertex VX478) (3S)-tetrahydro-3-furyl N-[((S,2R)-3-(4-amino-N
      isobutylbenzenesulfonamido)-1-benzyl- 2-hydroxypropyl] carbamate, is a potent HIV
      protease inhibitor and is currently undergoing clinical trials. The purpose of
      this study was the rapid identification of the phase I and II in vitro metabolite
      of 141W94 using mass spectrometry. Four different sources of liver S9 fractions
      were used for studying comparative in vitro metabolism of 141W94. They were
      obtained from Arochlor-induced rat, normal (untreated) rat, cynomolgus monkey and
      human livers. Selected incubations were supplemented with uridine diphosphate
      glucuronic acid and the reduced form of glutathione. The predominant species seen
      in the incubation mixture was the parent compound 141W94. Metabolites arising
      from ring opening to form the diol and carboxylic acid and oxidation of the
      tetrahydrofurran ring (formation of dihydrofuran) were identified. In addition,
      of the two monohydroxylated products identified, one resulted from hydroxylation
      on the aniline ring and the other from hydroxylation at the benzylic position.
      Two different glucuronides were also observed. Comparing the three species, very
      little metabolism was seen in the normal (non-induced) rat. The metabolic profile
      and extent of metabolism with induced rat, monkey and human S9 was similar.
      Induced rat S9 incubation showed the formation of two unique metabolites that
      were not seen in non-induced rat, monkey and human S9 fractions. They were the
      monohydroxylated glucuronide and a carbamate cleavage product. The metabolites
      were identified using mass spectrometry based on their molecular masses and
      fragmentation patterns.

PMID- 8755235
TI  - Stabilization of sialic acids in N-linked oligosaccharides and gangliosides for
      analysis by positive ion matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry of
      oligosaccharides and gangliosides normally causes loss of sialic acid,
      particularly when alpha-cyano-4-hydroxycinnamic acid is used as the matrix. In
      addition, the potential signal is split because both positive and, to a greater
      extent, negative ions are formed while signals are frequently complicated as the
      result of partial alkali-salt formation. In order to stabilize the sialic acid
      moieties under MALDI conditions and to divert all of the signal into the positive
      ion mode, a method involving their conversion into methyl esters has been
      developed. The method is relatively rapid and produces strong positive-ion
      signals from N-linked oligosaccharides containing sialic acid and from
      gangliosides. The latter compounds are stable, even in the presence of alpha
      cyano-4-hydroxycinnamic acid. They give abundant molecular (MNa+) ions, but with
      sufficient residual in-source fragmentation to allow the sequence of the sugar
      chain to be determined. The sialic acid residue is stable after methylation,
      irrespective of its linkage to the parent molecule.

PMID- 8755236
TI  - The use of stable isotope labeling and liquid chromatography/tandem mass
      spectrometry techniques to study the pharmacokinetics and bioavailability of the
      antimigraine drug, MK-0462 (rizatriptan) in dogs.
AB  - MK-0462 (rizatriptan) is a 5HT1D agonist being developed for the treatment of
      migraine. The assay for this substance in plasma and urine is based on HPLC with
      tandem mass spectrometry (MS/MS) detection. The procedure has been modified to
      include the simultaneous determination of the [triazole-13C2, 15N3-] stable
      isotope-labelled analogue for which the lower quantifiable limit was 0.1 ng mL-1.
      The assay has been applied to study the pharmacokinetics of MK-0462 after
      simultaneous oral and intravenous administration of the drug and its stable
      isotope-labelled analogue to dogs. The experiment afforded an estimate of plasma
      clearance concomitant with a precise measurement of the drug's oral
      bioavailability. The increasing use of LC-MS/MS in quantitative experiments may
      renew interest in stable isotopes as tools for pharmaceutical research.

PMID- 8755238
TI  - Matrix-assisted laser desorption/ionization mass spectrometry: a valid analytical
      tool in the dairy industry.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry has been employed
      to analyse the protein content of milk samples obtained with different
      pasteurization and sterilization methods. The data obtained indicate that the
      technique can be employed as a valid analytical tool in the dairy industry,
      allowing the monitoring of the functioning of the treatment plant in terms of
      physical parameters.

PMID- 8755237
TI  - Capillary liquid chromatography coupled with an ion trap storage/reflectron time
      of-flight mass spectrometer for structural confirmation of three recombinant
      protein isoforms.
AB  - Packed-capillary high-performance liquid chromatography (HPLC) was successfully
      coupled with an ion trap storage/reflectron time-of-flight mass spectrometer
      (LC/IT/reTOFMS) through an electrospray ionization interface for protein
      structural elucidation. Using the total-ion storage capabilities of the trap over
      a broad mass range and the high sensitivity from the packed capillary column with
      i.d. as small as 250 microns, high sensitivity peptide mapping in the low
      picomole range was demonstrated for the structural confirmation of three
      recombinant human nucleoside diphosphate kinase isoforms (NDPK, E.C. 2.7.4.6). A
      strategy combining chemical/enzymatic digestions as well as collisionally-induced
      dissociation (CID) in the electrospray source was successfully employed to infer
      the minor primary structural differences among the three recombinant proteins.
      This high sensitivity was achieved while also maintaining a resolution of nearly
      1500 for mass identification using the capabilities of the IT/reTOF device. A
      point mutation of serine 120 to glycine was verified between the wild-type NDPK A
      and its mutant (delta m = 30 u) by both selected-ion monitoring and ion-source
      CID of the protein fragment containing the mutation site. For the structural
      confirmation of the sequence of NDPK A and B (88% homology), two sets of
      chemical/proteolytic digests were generated independently and followed by LC/MS
      analysis of the molecular weight of each protein-generated fragment. The
      complementary information from the two chromatographic analyses allowed for
      sequence verification of the two protein isoforms. The experiments clearly
      demonstrated that the high concentration sensitivity of the capillary high
      performance liquid chromatographic separation together with the advantages of the
      IT/reTOF mass spectrometer could provide a low-cost, high-performance facility
      for protein analysis.

PMID- 8755239
TI  - Investigation of newly synthesized peptides by capillary zone
      electrophoresis/electrospray mass spectrometry.
AB  - A series of newly synthesized peptides (M(r) = 1600-2250 Da), corresponding to
      portions of the extracellular domain of human granulocyte-macrophage colony
      stimulating factor receptor alpha subunit have been examined by capillary zone
      electrophoresis/electrospray-mass spectrometry (CZE/ES-MS). The separation
      efficiency of CZE combined with the specificity of mass spectrometry allowed
      rapid and reliable identification of the target peptides and a number of
      associated side products. In solid-phase synthesis of peptides and small proteins
      such side products are inevitable, therefore the use of CZE and/or high
      performance liquid chromatography combined with mass spectrometry is gaining a
      central role in such synthesis procedures.

PMID- 8755240
TI  - The in vivo glyco-oxidation of alpha- and beta-globins investigated by matrix
      assisted laser desorption/ionization mass spectrometry.
AB  - Matrix-assisted laser desorption/ionization (MALDI) has been employed for the
      determination of molecular weights of alpha- and beta-globins obtained from blood
      samples of healthy and diabetic subjects. Glycated species, originating from the
      reaction of glucose with the proteins, are easily evident. The MALDI measurements
      allowed one to distinguish between simple glycation and glyco-oxidation processes
      of haemoglobin. In fact, together with the products arising from simple glucose
      condensation on the two proteins, compounds at different oxidation levels were
      evident. Due to its high specificity, MALDI must be considered a valuable tool
      for diagnosis in the diabetes field.

PMID- 8755241
TI  - CPx-type ATPases: a class of P-type ATPases that pump heavy metals.
AB  - ATP-driven heavy metal pumps represent a newly defined class of proteins that
      translocate toxic and essential metals across biological membranes. These
      transporters form a separate evolutionary branch of the ion-transporting P-type
      ATPases. We propose to call these enzymes CPx-type ATPases, based on the common
      novel feature of a conserved intramembranous cysteine-proline-cysteine or
      cysteine-proline-histidine motif.

PMID- 8755242
TI  - A duplicated catalytic motif in a new superfamily of phosphohydrolases and
      phospholipid synthases that includes poxvirus envelope proteins.

PMID- 8755243
TI  - TRAF proteins and meprins share a conserved domain.

PMID- 8755244
TI  - Pleckstrin's repeat performance: a novel domain in G-protein signaling?

PMID- 8755245
TI  - The biochemistry of polyadenylation.
AB  - During the synthesis of mRNA in the nucleus, 3'-ends are generated by
      endonucleolytic cleavage followed by polyadenylation. The machinery responsible
      for this simple reaction is surprisingly complex. In vitro reconstitution of 3'
      end processing has demonstrated the importance of cooperative interactions in RNA
      recognition and catalysis. However, the inventory of processing factors is still
      incomplete and important mechanistic questions have not yet been answered.

PMID- 8755246
TI  - Macromolecular structure information and databases. The EU BRIDGE Database
      Project Consortium.
AB  - The current status and future outlook of macromolecular structure databases and
      information handling, with particular reference to European databases, are
      reviewed. Issues concerning the efficiency with which data are represented,
      validated, archived and accessed are discussed in view of the fast growing body
      of information on structures of biological macromolecules.

PMID- 8755247
TI  - Not all Shc's roads lead to Ras.
AB  - The Shc proteins have been implicated in the Ras signaling pathway by virtue of
      their association with the Grb2 adaptor molecule. Several lines of evidence
      indicate that this association is indeed involved in Ras activation. More recent
      experiments in mammalian tissue culture cells suggest that domains unique to Shc
      isoforms, named CH1 and CH2, might be involved in a new network of protein
      protein interactions, and hint at other roles that Shc might play in addition to
      Ras activation.

PMID- 8755248
TI  - Topogenesis of inner membrane proteins of mitochondria.
AB  - Proteins of the inner mitochondrial membrane display a diverse range of
      topological arrangements. These proteins, encoded either by the nuclear or
      mitochondrial genomes, contain sequence determinants, so-called topogenic
      signals, which direct newly synthesized proteins to their final orientation in
      the membrane. The recent analysis of sorting pathways of a number of proteins
      highlights that these topogenic signals might act in different ways.

PMID- 8755249
TI  - PEST sequences and regulation by proteolysis.
AB  - In 1986, we proposed that polypeptide sequences enriched in proline (P), glutamic
      acid (E), serine (S) and threonine (T) target proteins for rapid destruction. For
      much of the past decade there were only sporadic experimental tests of the
      hypothesis. This situation changed markedly during the past two years with a
      number of papers providing strong evidence that PEST regions do, in fact, serve
      as proteolytic signals. Here, we briefly review the properties of PEST regions
      and some interesting examples of the conditional nature of such signals. Most of
      the article, however, focuses on recent experimental support for the hypothesis
      and on mechanisms responsible for the rapid degradation of proteins that contain
      PEST regions.

PMID- 8755250
TI  - Methods and reagents. Pouring sequencing gels the old-fashioned way.
AB  - Methods and reagents is a unique monthly column that highlights current
      discussions in the newsgroup bionet.molbio.methods-reagents, available on the
      internet. This month's column describes some different ways for pouring DNA
      sequencing gels, and there are some other tips as well. For details on how to
      partake in the newsgroup, see the accompanying box.

PMID- 8755251
TI  - Escherichia coli O 157 infection acquired in the laboratory.

PMID- 8755252
TI  - Guidance on control of tuberculosis.

PMID- 8755319
TI  - [Prognostic factors of early mortality in the 1st episode of hemorrhage caused by
      esophageal varices].
AB  - AIM: To assess the prognostic factors of early mortality in cirrhotic patients
      with the first variceal bleeding episode. PATIENTS AND METHODS: Fifty-five
      cirrhotic patients with endoscopic evidence of variceal bleeding treated with
      sclerotherapy during emergent endoscopy were included. RESULTS: Permanent
      hemostasis was obtained in 36 patients (65.5%). Fourteen (25.4%) patients died
      within six weeks of the bleeding episode. Twenty-four variables obtained at
      admission and in the following days were compared between patients who survived
      (n = 41), and died (n = 14). In the univariate analysis the following variables
      were related to early mortality: prothrombin ratio (p = 0.04), the presence of
      ascites (p = 0.004) and encephalopathy (p = 0.06), albumin (p = 0.01), Child-Pugh
      score (p = 0.0003), hemostasis during endoscopy (p = 0.002), absence of
      rebleeding at 24 hours (p = 0.01) and early rebleeding (within five days after
      the bleeding episode) (p = 0.006). Multiple logistic regression identified the
      Child-Pugh score (OR 11.86, CI 95% 2.54-55.48; p = 0.001) and early rebleeding
      (OR 6.27, CI 95% 1.29-30.44; p = 0.02) as prognostic independent factors of early
      mortality. CONCLUSIONS: The degree of hepatic failure and early rebleeding are
      prognostic independent factors of early mortality in cirrhotic patients after the
      first variceal bleeding episode.

PMID- 8755320
TI  - [Prevalence of Helicobacter pylori infection in gastric adenocarcinoma and
      chronic gastritis].
AB  - AIM: To describe the prevalence of Helicobacter pylori infection in patients with
      gastric adenocarcinoma, and compare it with that of patients with chronic
      gastritis. METHODS: Fifty-four patients with endoscopically diagnosed gastric
      cancer (later confirmed histologically as gastric adenocarcinoma), and 60
      patients with histologic chronic gastritis were studied. Age and sex distribution
      was similar in both groups. At endoscopy biopsy specimens were taken from antrum
      and body (H&E stain, Gram stain and culture). RESULTS: H. pylori was found in 95%
      (95%CI = 86-98%) of patients with chronic gastritis, and in 41% (CI = 29-54%) of
      patients with gastric adenocarcinoma (p < 0.001). H. pylori was present in
      malignant tissue in 13% (CI = 6-24%) of cases, a significant lower (p < 0.01)
      percentage than in the gastric antrum and body. CONCLUSION: The prevalence of H.
      pylori infection diagnosed by microbiologic and histologic methods in patients
      with gastric adenocarcinoma (41%) is significantly lower than in patients with
      chronic gastritis, its premalignant lesion. H. pylori was present less frequently
      in malignant tissue than in endoscopically normal mucosa.

PMID- 8755321
TI  - Oral human recombinant epidermal growth factor in the treatment of patients with
      duodenal ulcer.
AB  - The epidermal growth factor has been shown to be mucoprotective and to accelerate
      healing of gastroduodenal ulcers in animals. A prospective, positively controlled
      clinical trial was conducted. Seventy five patients with duodenal ulcer were
      randomly distributed in three groups to receive oral human recombinant epidermal
      growth factor in 1% carboxymethyl cellulose at two different doses (450 mg or 600
      mg/day), or cimetidine. Treatment was administered up to a maximum of 6 weeks.
      The most important assessment criteria was the proportion of patients healed
      after 2, 4 and 6 weeks of treatment determined by endoscopy. Treatment with both
      doses of epidermal growth factor showed a long-term healing effect in 76.5% at 6
      weeks vs 92.5% with cimetidine (p = N.S.). The evolution of the clinical symptoms
      was similar in the three groups. Adverse reactions were not detected in any of
      the patients included in this study. To our knowledge, this is the first report
      on the oral use of epidermal growth factor in humans.

PMID- 8755323
TI  - [Infectious gastroenteritis in relapses of inflammatory bowel disease.
      Therapeutic implications].
AB  - The incidence and clinical importance of infectious gastroenteritis was studied
      in 67 consecutive relapses of inflammatory bowel disease (IBD). A stool culture
      was done in every case before starting treatment. Stool culture was positive in 6
      relapses (8.9%): Four were exacerbations of ulcerative colitis and two of Crohn's
      disease (8.8% in ulcerative colitis vs 9% in Crohn's disease; NS). The
      microorganisms isolated were Campylobacter jejuni in three cases, Salmonella
      enteritidis in two and Staphylococcus aureus in one case. There were not clinical
      differences between patients with positive and negative stool culture. Treated
      with antibiotics, stool cultures became negative in all of them but only in three
      the disease was controlled. The other three had to be treated with
      corticosteroids to achieve remission. We conclude that stool culture should be
      practised in all relapses of IBD and in case of positivity, antibiotic therapy
      should be started. With this approach the use of corticosteroids can be avoided
      in some patients.

PMID- 8755324
TI  - [Nitric oxide and oxidative metabolism: heads or tails in inflammatory gastric
      disease].

PMID- 8755325
TI  - [Dementia caused by bacterial overgrowth in a patient with Billroth II
      gastrectomy].
AB  - We report the case of a patient in the Psychiatric Department who complained of
      progressive impairment of cerebral functions consistent with dementia, diarrhea
      and fecal incontinence in the last few months. His medical history included a
      Billroth II gastrectomy for gastric ulcer. Biochemical tests detected cobalamin
      deficiency, without megaloblastic anemia, and an abnormal Schilling test that was
      not due to intrinsic factor deficiency. Once other causes of cobalamin deficiency
      were ruled out, we considered it as a deficiency disease due to blind loop
      syndrome. Treatment with parenteral vitamin B complex and long term oral
      antibiotic therapy allowed the complete and permanent resolution of neurologic
      and digestive symptoms. We consider this case to be interesting because it shows
      the existence of curable dementias and the usefulness of taking into account
      bacterial overgrowth, usually underestimated, as an entity that can produce a
      variety of disorders.

PMID- 8755326
TI  - [Villous adenoma of the appendix caused acute appendicitis].
AB  - Villous adenoma of the appendix is a rare pathologic entity, the treatment is
      controversial. We describe the case of a patient complaining of abdominal pain
      that was diagnosed as acute appendicitis. Pathological examination of the
      surgical specimen revealed a villous adenoma of the appendix. We comment the
      therapeutic options and we review the literature about this pathological entity.

PMID- 8755327
TI  - [Burkitt's lymphoma: atypical localization].
AB  - We present a case of Burkitt's lymphoma, American type, with massive abdominal
      involvement, in a 11 years old boy, who presented with mucous-cutaneous paleness,
      cephalalgia and melaena. The localization of the lesion in the gallbladder and
      the rectum is stressed as being exceptional. We emphasize the importance of a
      rapid diagnosis to start early chemotherapy because this lesion grows rapidly. In
      our case after eight days of chemotherapy treatment there was a 75% reduction of
      the tumor mass.

PMID- 8755328
TI  - [Pain and jaundice secondary to hemobilia resolved by ERCP and endoscopic
      sphincterectomy].
AB  - We report the case of a patient with hemobilia resulting from a liver biopsy
      where the performance of the endoscopic sphincterectomy solved the jaundice and
      the pain of the patient. ERCP has been used previously in the diagnosis of
      biliary and pancreatic tumors that manifested themselves as an hemobilia. The
      therapeutic utilization of endoscopic sphincterotomy had been described rarely in
      this type of bleedings. We recommend endoscopic retrograde
      cholangiopancreatography and sphincterotomy in the cases of hemobilia with severe
      abdominal pain resulting from the accumulation of clots inside the biliary tract.

PMID- 8755329
TI  - [Splenic infarction].
AB  - A 53-year-old male suffered splenic infarction etiologically related to atrial
      fibrillation and non-obstructive hypertrophic cardiomyopathy. The main clinical
      manifestations were a one-month history of epigastric and left upper quadrant
      pain, with tenderness to palpation in the later zone. Laboratory tests revealed a
      slight leucocytosis (14.700) with left shift and a marked increase in LDH
      concentration (945 IU). Abdominal CAT and arteriography established the
      diagnosis, Echography proved normal. Patient evolution was satisfactory with
      conservative medical treatment. We conclude that splenic infarction should be
      considered in all cases of acute or chronic pain in the left hypochondrium. The
      diagnosis is established by CAT, arteriography and hepatosplenic gammagraphy.
      Medical management is initially advocated, surgery being reserved for those cases
      involving complications or in which diagnosis is not clear. Emphasis is placed on
      the main etiological, clinical, diagnostic and management characteristics of
      splenic infarction.

PMID- 8755331
TI  - [Tumor recurrence in laparotomy scar: it is not only a problem of laparoscopic
      surgery].

PMID- 8755330
TI  - [Gastric plexosarcoma].

PMID- 8755332
TI  - [Papillary cystic tumor of the pancreas: apropos of a case].

PMID- 8755333
TI  - [6-Mercaptopurine and inflammatory bowel disease].

PMID- 8755334
TI  - Adaptive optimization and the harvest of biological populations.
AB  - Adaptive management of renewable biotic resources accounts explicitly for
      uncertainties in system responses to management and recognizes the importance of
      reducing uncertainties while pursuing other management goals. An adaptive
      approach to the harvest of wildlife populations that are subject to (1)
      uncontrollable environmental variation, (2) uncertainties about the appropriate
      characterization of resource dynamics, (3) limitations on the controllability of
      harvest rates, and (4) uncertainties as to population status, expressed as
      sampling variation in the monitoring of populations and habitats, is described.
      Adaptive management is framed in terms of maximizing long-term harvest value
      against a background of various kinds and degrees of uncertainty, with an
      emphasis on structural uncertainty. By an appropriate extension of the "system
      state," adaptive optimization can be defined in terms of Markov decision
      processes. Solution algorithms are described for systems that are subject to
      structural uncertainty and are either partially or completely observable.
      Adaptive optimization is illustrated with an example in waterfowl harvest
      management that incorporates uncertainty in the relationship between harvest
      rates and survivorship.

PMID- 8755335
TI  - ESS patterns: adding pairs to an ESS.
AB  - The notion of a pattern of evolutionarily stable strategies was introduced by
      Cannings and Vickers in 1988 (J. Theor. Biol. 132:387-420). In this paper a
      specific class of patterns is considered. Suppose that there is an evolutionarily
      stable strategy (ESS) on some set of n strategies {1,2,...,n} and that new
      strategies {n + 1,n + 2,...,n + k} are added. Supposing that for this new
      enlarged conflict there is still an ESS on {1,2,...,n} and also that there are
      ESSs on {n + i,j} for 1 < or = i < or = k and j epsilon Si [symbol: see text]
      {1,2,...,n}, the authors investigate the restrictions on the Si. These
      restrictions are related to certain properties of strong tournaments introduced
      by Reid and Beineke. We also specify, given the Si, what ESSs of the form {n +
      i,n + j} can be added.

PMID- 8755336
TI  - A model of wound-healing angiogenesis in soft tissue.
AB  - Angiogenesis, or blood vessel growth, is a critical step in the wound-healing
      process, involving the chemotactic response of blood vessel endothelial cells to
      macrophage-derived factors produced in the wound space. In this article, we
      formulate a system of partial differential equations that model the evolution of
      the capillary-tip endothelial cells, macrophage-derived chemoattractants, and the
      new blood vessels during the tissue repair process. Chemotaxis is incorporated as
      a dominant feature of the model, driving the wave-like ingrowth of the wound
      healing unit. The resulting model admits traveling wave solutions that exhibit
      many of the features characteristic of wound healing in soft tissue. The steady
      propagation of the healing unit through the wound space, the development of a
      dense band of fine, tipped capillaries near the leading edge of the wound-healing
      unit (the brush-border effect), and an elevated vessel density associated with
      newly healed wounds, prior to vascular remodeling, are all discernible from
      numerical simulations of the full model. Numerical simulations mimic not only the
      normal progression of wound healing but also the potential for some wounds to
      fail to heal. Through the development and analysis of a simplified model, insight
      is gained into how the balance between chemotaxis, tip proliferation, and tip
      death affects the structure and speed of propagation of the healing unit.
      Further, expressions defining the healed vessel density and the wavespeed in
      terms of known parameters lead naturally to the identification of a maximum
      wavespeed for the wound-healing process and to bounds on the healed vessel
      density. The implications of these results for wound-healing management are also
      discussed.

PMID- 8755337
TI  - Spatially explicit models for the population dynamics of a species colonizing an
      island.
AB  - We construct reaction-diffusion models for the population dynamics of a species
      colonizing an island from a source population on a continent. We view the source
      population as inducing a density or flux of immigrants onto the island and
      interpret colonization as succeeding if the population on the island is predicted
      to persist even when immigration from the continent is stopped. To capture the
      observation that a sufficiently large population or density must be attained for
      colonization to succeed, we assume Allee (i.e., bistable) dynamics rather than
      logistic dynamics for the colonizing population. We consider the cases of
      colonization in both the absence and presence of a competitor. We use reaction
      diffusion theory, especially comparison methods and sub- and supersolutions, to
      determine how parameters such as the distance from the continent to the island
      and the dispersal, birth and mortality rates, carrying capacity, and minimum
      viable population density of the colonizing species affect the outcome of the
      attempted colonization. In the case of colonization in the presence of a
      competitor we consider a number of scenarios involving different types and
      strengths of competition. Our analysis permits us to draw conclusions about the
      characteristics of a species that make it a good colonizer.

PMID- 8755338
TI  - Mandibular form and function in North American and European Adapidae and
      Omomyidae.
AB  - Previous experimental and comparative studies among a wide variety of primate and
      nonprimate mammals provide a unique source of information for investigating the
      functional and phylogenetic significance of variation in the masticatory
      apparatus of Eocene primates. To provide a quantitative study of mandibular form
      and function in Eocene primates, the scaling of jaw dimensions and the
      development of symphyseal fusion was considered in a broad sample of North
      American and European Adapidae and Omomyidae. Statistical analyses indicate a
      significant size-related pattern of symphyseal fusion across Eocene primates,
      with larger taxa often having a greater degree of fusion than smaller species;
      this trend is also evident at the family level. As adapids are mostly larger than
      omomyids and these taxa show allometry of symphyseal fusion, this may explain why
      no omomyids evince complete fusion. Controlling for jaw size, species with
      greater symphyseal fusion tend to have more robust jaws than those with a lesser
      amount of fusion. Upon further examination, a primary reason why adapids have
      more robust mandibles than omomyids is associated with the presence of taxa with
      fused symphyses, and thus more robust jaws, in the adapid sample, whereas no
      omomyids have fused symphyses. In addition, there is little indication of a
      dietary effect, as measured by molar shear-crest development, on symphyseal
      fusion. Moreover, as there is no correlation between molar shear-crest
      development and skull size, this also points to the absence of a size-related
      pattern of dietary preference underlying the allometry of symphyseal fusion.
      Based on the interspecific and ontogenetic allometry of symphyseal ossification
      in Eocene primates, jaw-scaling patterns are used to further examine the
      functional determinants of fusion in this group. This study indicates that
      greater dorsoventral shear during mastication is a more likely factor than
      lateral transverse bending ("wishboning") in the evolution of symphyseal fusion
      among "late-fusing" mammals like adapids and omomyids. Given that wishboning is
      an important functional determinant of symphyseal form in recent anthropoids,
      apparently the evolutionary development of marked wishboning occurs only in taxa
      that shift the timing of fusion to a growth stage preceding the onset of weaning
      (before adult masticatory patterns are fully developed) and perhaps first
      ossified the symphysis to counter elevated dorsoventral shear stress. As early
      anthropoids probably consisted of members varying interspecifically and
      ontogenetically in the degree of ossification, it is especially informative to
      analyze the adaptive setting in which anthropoid symphyseal fusion evolved from a
      similar primitive "prosimian" perspective. Finally, since taxa with fused
      symphyses are widely distributed across mammals, a similar analytical framework
      could be directed profitably at unraveling the functional and evolutionary
      significance of symphyseal fusion in other mammalian clades.

PMID- 8755339
TI  - A tendon-locking mechanism in two climbing rodents, Muscardinus avellanarius and
      Micromys minutus (Mammalia, Rodentia).
AB  - Having compared the microanatomy of the toes of a terrestrial to two climbing
      species, adaptations were found in the flexor tendons and in the integument. In
      contrast to Crocidura russula, both Muscardinus avellanarius and Micromys minutus
      have a tendon-locking mechanism (TLM) that is engaged when the middle phalanx is
      bent. A ventral thickening of the flexor tendon is situated deep to a thickened
      portion of the ventral tendon sheath. When twigs or stalks are grasped, the TLM
      allows less muscular energy to be expended. In C. russula glands are restricted
      to the terminal pads, but in the climbing species they occur in the sole of the
      toes as well. In the reed-living M. minutus knob-shaped integumental thickenings,
      together with the digital pads, stabilize the grip. In contrast the arboreal M.
      avellanarius often climbs thick branches and shows adaptations for pressing the
      sole of the feet against the surface. Thereby the tendon attached to the plantar
      integument of the toes transfers the muscle force directly to the bark. Unlike
      the other digits on the forefeet of both climbing species, no TLM is present in
      the anterior digit. In M. minutus this short digit is twisted towards the palm
      and, with the carpal pads, provides an abutment against the grasping fingers. In
      M. avellanarius the anterior digit has very thin tendons and is that much reduced
      in length that it is completely integrated into the digital pad where it acts, at
      best, as a lateral support of the pad.

PMID- 8755340
TI  - Phenotypic plasticity in skull and dental morphology in the prairie deer mouse
      (Peromyscus maniculatus bairdii).
AB  - Morphologists and systematists have long suspected that dietary consistency can
      affect skull and dental form in mammals. We examined plasticity of skull shape
      and tooth morphology in prairie deer mice (Peromyscus maniculatus bairdii) by
      feeding mice diets that differed in consistency but not nutritional quality.
      Shape differences were analyzed qualitatively and quantitatively, using both
      landmark-based morphometrics and traditional distance measurements. Mice fed a
      gruel made of laboratory chow soaked in water differed from those fed hard blocks
      of chow by a slight anterior shift in the incisor tips, a narrowed zygomatic
      plate, a reduction in size of the masseteric tubercles, an overall decrease in
      skull size in lateral view, and an increase in overall size in ventral view.
      Disparities between our results and previous studies may be due to the
      differences in behavior between the inbred, relatively inactive laboratory
      strains commonly used in experimental studies and the outbred, constantly active
      species used here. Also, in contrast to previous studies, the statistical
      analysis employed here took into account both family relationships of the animals
      and the large number of statistical comparisons performed. Failure to consider
      these factors would have resulted in an exaggerated estimate of the effects of
      diet on skull form and may taint other studies that have explored the same
      aspects of plasticity.

PMID- 8755341
TI  - Expanded programme on immunization (EPI). Immunization in the English-speaking
      Caribbean.

PMID- 8755342
TI  - [Neurocutaneous disorders. Diagnostic criteria and follow-up protocols:
      introduction].

PMID- 8755343
TI  - [Neurofibromatosis type I (NF1): peculiarities and complications].
AB  - The clinical, radiological and genetic peculiarities of neurofibromatosis type 1
      (NF1) or the von Recklinghausen disease are shown. The most common complications
      of this syndrome are presented. These are optic pathways gliomas and some other
      tumors of the nervous system and of any other location in the body; oseous
      alterations with skoliosis, pseudoarthrosis and facial dysplasias as the most
      important; aqueductal stenosis that frequently appears at the puberty or at adult
      life; an intellectual level lower than their brothers and sisters without NF1,
      and some less frequent complications such as endocrinological disorders and
      corpus callosum agenesis.

PMID- 8755344
TI  - [Neurocutaneous disorders with achromic spots. Tuberous sclerosis of Bourneville.
      Diagnostic criteria and follow-up protocol].

PMID- 8755345
TI  - [Neurocutaneous disorders with large dyschromia: incontinentia pigmenti, achromic
      nevus].

PMID- 8755346
TI  - [Neurocutaneous melanosis].

PMID- 8755347
TI  - [Neurocutaneous syndromes with predominant vascular anomalies].

PMID- 8755348
TI  - [Natural evolution of neurocutaneous syndrome in adults].
AB  - Neurofibromatoses (NF1 and NF2) are genetic diseases with an extremely wide range
      of manifestations, particularly NF1. In order to gain insight into their
      prognosis, we have conducted a follow-up study of 100 patients with
      neurofibromatoses, 89 NF1 patients and 11 NF2 patients all of them presenting
      neurological manifestations. Four deaths occurred in the NF1 group (3
      neurofibrosarcomas) and two in the NF2 group (after neurosurgery). We describe a
      series of NF1 brainstem tumors as being pilocytic astrocytomas, much less
      aggressive than non-NF1 brainstem tumors but more symptomatic than brainstem UBOs
      ('unidentified bright objects') in NF1. The series of optic nerve tumors also
      demonstrate the poor and non-progressive evolution of tumors with the same
      histopatological estructure. Hydrocephalus related to aqueductal stenosis is a
      frequent and tratable manifestation in NF1 patients. Data are presented which
      suggest that a severe form of NF2 is much more frequent than a mild form but it
      is rule that number and progressivity of tumors render the prognosis always
      severe in NF2 patients. A long term follow-up study has been carried among 20
      patients with tuberous sclerosis: patients who presented seizures before the age
      of 5 years have mental retardation in spite of disappearing, often spontaneously,
      the seizures. The initial symptoms in Von Hippel-Lindau patients depend often on
      the hemangioblastoma of the spinal cord and a strict control is proposed for
      patients with risk of suffering spinal-cerebello-retino hemangioblastomatosis.
      Other phakomatoses are also being considered in their general prognosis.

PMID- 8755349
TI  - [Citations and medical journals in Spanish].

PMID- 8755350
TI  - [Relationship between primary and specialized care in neurology].

PMID- 8755351
TI  - [The use of SPECT with 201Tl in the evaluation of brain tumors].
AB  - There is increasing interest in the literature regarding the use of SPECT (single
      photon emission computed tomography) with 201Tl in the evaluation of cerebral
      tumours. Thallium (201Tl) is one of the isotopes most commonly used in studies of
      the myocardium and in the diagnosis of various tumours. Normal brain takes up
      very little 201Tl, but in viable tumour tissue the 201Tl becomes intracellular
      and is rapidly cleared from the blood stream. Such cerebral tumour uptake is
      related to changes in the permeability of the blood-brain barrier, regional blood
      flow and transport by means of the Na(+)-K+ adenosine triphosphate pump. Once the
      SPECT images have been obtained following administration of the radioisotope, one
      can calculate the indices of early and of late uptake together with the retention
      index. The usefulness of SPECT in the preoperative detection of malignant
      expansive pathology, choice of tumour region during stereotaxic biopsy, control
      of tumour reproduction and their differentiation from post-radiotherapy necrotic
      tissue, and evaluation of chemotherapy in treatment of cerebral tumours are
      analyzed. Finally the application of SPECT in metastatic conditions and the
      differential diagnosis of expansive lesions is considered.

PMID- 8755352
TI  - [Evaluation of memory in neuropsychological clinic].
AB  - Following an introduction in which the history of the clinical evaluation of
      memory is briefly reviewed, a methodology is described for the evaluation of
      patients complaining of memory loss, or in whom such deterioration is observed,
      although it was not the reason for consultation. The main instruments currently
      available for evaluation are described. Methodological problems posed by the use
      of these instruments, and the precautions necessary when interpreting the data
      thus obtained, are discussed. The conclusion summarizes the use of the proposed
      methodology, both in the differential diagnosis of changes of memory and in
      establishing individual rehabilitation programmes or compensation.

PMID- 8755353
TI  - [Neuroimaging techniques in the Gilles de la Tourette syndrome].
AB  - Tourette's syndrome (GdT) is a chronic neuropsychiatric disorder of unclear
      etiology characterized clinically by the presence of motor and phonic tics as
      well as a variety of behavioral and cognitive abnormalities such as Obsessive
      Compulsive Disorder (TOC) and Attention Deficit Hyperactivity Disorder (ADHD).
      Dopaminergic pathway and movement control related structures may have some
      implications for pathogenesis. Neuroimaging techniques may yield relevant data
      for a better understanding of the symptoms and physiopathology of this disease.
      Among them, functional isotopic techniques such as PET and SPECT and other like
      quantitative EEG are the most remarkable. In this article we intend to perform a
      thorough review of the most recent literature, contributing with our own
      experience and discuss the pathogenesis of GdT.

PMID- 8755354
TI  - [Quality of life and migraine].
AB  - OBJECTIVE: Nowadays, quality of life is considered to be important both in
      clinical investigation and patient care. Migraine is a particularly disabling
      illness, with a pronounced effect on general health and on the ability to take
      part in social activities. We review the instruments used for measuring quality
      of life and the published studies in which the relationship between migraine and
      quality of life is analyzed. MATERIAL AND METHOD: In spite of increasing interest
      in quality of life and the means by which this is measured, there are many
      problems involved in studying this correctly since there is no agreement as to
      its definition or how to measure it. In recent years, most of the studies carried
      out have assessed the socio-economic cost of headache. However, at present,
      studies tend to focus on the human cost of the quality of life when suffering
      from headache. Migraine patients have a poorer quality of life than the general
      population and other populations with chronic illnesses which have always been
      considered to be severely disabling. CONCLUSION: Research should be aimed at
      finding the specific and/or generic measures necessary to improve quality of life
      while suffering from headache. In the future, the aim of new treatments should be
      to eliminate the pain of the acute crisis and restore functional capacity, reduce
      the period of disability and improve quality of life.

PMID- 8755355
TI  - [Prospective study of the differences between the syndromes of infantile absence
      epilepsy and syndromes of juvenile absence epilepsy].
AB  - In this prospective study of the differences between the epileptic syndrome of
      absence attacks in the child (EAN) and the syndrome of juvenile absence attacks
      (EAJ), the author considers the characteristics of these syndromes in order to
      differentiate their various aspects, namely clinical features, complementary
      tests, course and prognosis. These cases are from a series of 6,299 epileptic
      patients. One of the objectives of a prospective study begun in 1970 was to
      evaluate the clinical course of all cases in which valproic acid was used.
      Valproic acid is known to be most effective in the basic crises of these two
      syndromes, namely the typical absence attacks. It is therefore an analysis of the
      clinical features and their subsequent course and prognosis when thus treated,
      since a retrospective study including a much larger number of patients would not
      be considered to be satisfactory in view of the 'bias' due to only some patients
      having access to treatment with this drug. The author analyzes 138 cases of EAN
      and 42 cases of EAJ seen between 1970 and the end of 1995. These syndromes,
      particularly EAN, have always been considered to have an excellent prognosis. The
      author tries to show from the point of view of long term follow-up, that absence
      attacks may not only persist into adult life but also be associated with other
      types of crises which worsen the prognosis. Thus, for instance, in EAN 50% of the
      cases show generalized tonic-clonic seizures on long-term follow-up. In EAJ the
      corresponding figure is 76.1%. This data modifies previous ideas as to the benign
      course of these syndromes when they are followed-up for a long period. The basic
      criteria were: a first visit after 1970 and an age of onset between 3 and 10
      years for EAN and over 10 years for EAJ. In all cases there was the following
      conditions, onset by absence attacks, lack of permanent neurological or
      psychological disorders, and a video-EEG recording of a typical generalized EEG
      during an attack.

PMID- 8755356
TI  - [Syringomyelia, scoliosis and idiopathic Arnold-Chiari malformations: a common
      etiology].
AB  - INTRODUCTION: The major theories of the pathogenesis of idiopathic syringomyelia
      (SMI), idiopathic scoliosis (ESCID) and the Arnold-Chiari malformation (ARCH) are
      reviewed. A new theory involving a common pathology for SMI, ESCID and ARCH is
      proposed. Its confirmation depends on the presence of an abnormally low position
      of the conus medullaris (CM) in patients with SMI. Material and method. Of 292
      patients with syringomyelia (SM), 231 patients with SMI were selected, and 55 of
      these were chosen in whom the level of the conus medullaris (NCM) could be
      determined, together with figures for SMI, ESCID and ARCH by magnetic resonance
      (RM). The position of the conus medullaris in 50 patients who did not have SM,
      ESCID nor ARCH on cervical and lumbar RM was determined. RESULTS: 96.54% of
      patients with SMI showed some descent of the cerebellar tonsils. 72.97% of the
      SMI patients also had ESCID: 74.07% of the patients in whom the conus medullaris
      was seen had scoliosis and a low position of the conus medullaris. 6% of the
      control group had a conus medullaris at the level of the body of L1, whilst
      84.21% of the patients with SMI had a partial or complete image of the conus
      medullaris at this level. In these patients, an unusually low position of the
      conus medullaris was confirmed. CONCLUSIONS: The unusually low position of the
      conus medullaris in SMI and its close relationship to ARCH and ESCID make it
      likely that the same pathogenic mechanism is shared by them all. Abnormal
      asynchromy of growth of the notochord and the spinal cord gives rise to a
      distinct disorder which shows as different syndromes.

PMID- 8755357
TI  - [Etiology in complex partial epilepsy. II. Correlation between EEG topography and
      neuroimaging].
AB  - Neuro-imaging studies (NI) in patients with complex partial seizures (CPC)
      demonstrate the epileptogenicity of a more or less localized underlying lesion.
      Correlation with the topography of the EEG focus permits affirmation of the
      origin. We analyze anomalies on NI and on the EEG of 151 patients with CPC. The
      EEG was abnormal in 128 and showed a unilateral epileptic focus in 117. NI was
      focal and unilateral in 72 of the 102 abnormal cases. Topographic correlation was
      78.5%. This close correlation in our series makes us consider the localized
      lesions to be the probable aetiological factor.

PMID- 8755359
TI  - [Perinatal asphyxia, hypoxic-ischemic encephalopathy and neurological sequelae in
      full-term newborns. II. Description and interrelation].
AB  - INTRODUCTION: There have been several attempts to relate either perinatal
      asphyxia at birth or abnormal neurological findings after asphyxia in neonatal
      period (hypoxic-ischemic encephalopathy), to outcome. OBJECTIVE: To investigate,
      in full-term infants, the relation between perinatal asphyxia, hypoxic-ischemic
      encephalopathy and neurologic sequelae at follow-up, and to define the main
      neurologic sequelae (cerebral palsy, mental retardation, neonatal death).
      Material and method. Prospective epidemiologic study over perinatal asphyxia in
      term neonates born in Universitary Hospital San Juan (Alicante, Spain) between
      November 1991-February 1995. Perinatal asphyxia was graded as non severe (1
      minute Apgar score < or = 6 and/or umbilical artery pH < 7.20, with abnormal
      fetal heart rate patterns and/or meconium-stained amniotic fluid, and the need
      for immediate neonatal resuscitation) and severe (1-minute Apgar score < or = 3
      and umbilical artery pH < 7.10). Hypoxic-ischemic encephalopathy was graded as
      mild, moderate and severe based on classification of Levene and Sarnat & Sarnat.
      The abnormalities on psicomotor development are based in the neurologic 'alert
      signs' and in the neurologic sequelae; this sequelae was graded as mild, moderate
      and severe based on classification of Finer and Amiel-Tison. The relationships
      between these variables are studied by univariant and multivariant analysis
      (Cox's regression). RESULTS: The incidence of neurologic sequelae, in 115
      asphyxiated full-term infants follow-up at least 12-24 months, was 16.5%; 4 cases
      of severe sequelae, 4 moderate and 11 mild. The overall asphyxia-related infant
      mortality rate was 0.87/1.000 live births. The main sequelae detected at follow
      up was motor disability, and other disabilities like mental retardation,
      epilepsy, sensorial defects, were infrequents. The incidence of cerebral palsy
      was 0.87/1.000 live births, and 2.6% asphyctic term neonates. We found a
      statistically significant (p < 0.001) association between severity of perinatal
      asphyxia and/or evidence of hypoxic-ischemic-encephalopathy and the neurological
      development at follow-up. Of the several factors associated to risk of neurologic
      sequelae on univariant analysis, only two were independently associated on
      multivariant analysis: severe perinatal asphyxia (RR = 2.82; IC = 1.07-7.39) and
      postasphyctic encephalopathy (RR = 4.17; IC = 1.48-11.75). CONCLUSIONS: Most
      survivors of perinatal asphyxia do not have adverse sequelae. The best predictive
      tool for the neurological prognosis at follow-up was severe perinatal asphyxia at
      birth and evidence of encephalopathy in neonatal period. Our study confirm that
      perinatal asphyxia is infrequently the cause of cerebral palsy and mental
      retardation.

PMID- 8755358
TI  - [Prognostic value of data from clinical, EEG and neuroimaging assessment in
      epilepsy with complex partial seizures].
AB  - INTRODUCTION: The well-known etiology, length of active epilepsy, partial or
      mixed seizure types and high frequency of seizures before treatment relate with a
      worst prognosis for seizures control. We have attempted to prove these factors in
      our study. METHOD: We analyzed the electro-clinical characteristics, evolution
      and etiology of seizures in 151 patient with several type of partial epilepsy.
      Subsequently, we related the estimated improvement with diverse variables.
      RESULTS: A significant statistically difference appeared as for seizures
      frequency at onset, existing among 15% to 44.3% more patient in which the
      frequency descended to more of 50% when the initial frequency was more than one
      to the month. Upon relating the improvement with the MR anomaly also appeared
      significant difference: there was between 7.9% and 73.7% more patient with
      hypersignal on long TR sequences in the group that did not decrease the frequency
      of their crisis to more than 50%.

PMID- 8755360
TI  - [Disappearance of migraine crises in two patients with male infertility treated
      with human chorionic gonadotropin/human menopausal gonadotrophin].
AB  - Two patients aged 52 and 31 respectively, treated for male infertility with
      gonadotrophins (LCG/LMG), showed marked improvement of their migraine crises
      associated with a typical aura which had been present since puberty. Changes in
      the number, motility and morphology of the spermatozoids were seen in the
      seminogram. The plasma concentrations of FSH, LH, testosterone an 17-beta
      oestrodiol were within normal limits. After three months of empirical treatment
      with LCG/ LMG (to stimulate spermatogenesis) the migraine crises ceased and the
      patients are still free of migraine after 32 and 26 months respectively. The
      relationship between migraine and the sex hormones is discussed, in the context
      of current knowledge of the psysiopathology of migraine and the beneficial
      effects obtained after treatment with LCG/LMG. We have not found any reference in
      the literature to the use of gonadotrophins in the treatment of migraine with a
      typical aura.

PMID- 8755361
TI  - [Neuroimaging, CT and MR brain findings in a case of McCune-Albright syndrome].
AB  - McCune-Albright syndrome is characterized by the triad of polyostotic fibrous
      dysplasia, precocious puberty, cutaneous pigmentation and cafe-au-lait spots. A
      23-year-old woman with McCune-Albright is reported. Findings on CT scan and
      magnetic resonance imaging of the skull in an affected girl with McCune-Albright
      syndrome are shown, and also the histopathological study of the right temporal
      bone biopsy.

PMID- 8755362
TI  - [Isolated lesion of the Edinger-Westphal nucleus in topographical relation with a
      post-traumatic mesencephalic hematoma].
AB  - INTRODUCTION: From the relevant literature, it would seem that the commonest
      single cause of lesion of the third cranial nerves is indirect, accompanying
      intracranial traumas. From multiple clinical observations however, it seems that
      many of these cases may be due to lesions of the mesencephalum which nevertheless
      have rarely been identified by current imaging techniques. Clinical case. We
      describe the clinical observation of isolated pupil involvement, attributed to a
      lesion of the Edinger-Westphal nucleus as a consequence of a mesencephalic
      haematoma in the context of closed craneo-encephalic trauma. In our review of the
      literature, we have not found any other such case. CONCLUSIONS: We briefly review
      the most frequently involved mechanisms implicated in the genesis of lesions of
      the third cranial nerves at different sites and the different changes seen in the
      pupil in each case, together with the characteristics and pathogenesis of the
      lesions produced in the mesencephalum as a consequence of intracranial trauma. We
      emphasize the importance of our case as being the first time an isolated lesion
      of the Edinger-Westphal nucleus has been described in topographic relation to a
      mesencephalic haematoma.

PMID- 8755363
TI  - [Pontine hemorrhage as a cause of peripheral facial paralysis].
AB  - Bell's palsy is the most frequent type of peripheral facial nerve paralysis.
      Nevertheless there are other less frequent causes of peripheral facial palsy,
      among which, we can find lesions in the brain stem affecting the seventh cranial
      nerve nucleus or its fibers. These lesions of the pons which paralyze the muscles
      of the face are often accompanied by lesions to other structures in the vicinity
      of the nucleus. We present the case of peripheral facial nerve palsy caused by
      hemorrhage in the pons, seen both on brain CT-scan and MRI, which affected the
      nucleus of the seventh cranial nerve and was not accompanied by any other
      clinical manifestations due to lesions of structures placed in the vicinity of
      this nucleus.

PMID- 8755365
TI  - [A case of a 66-year-old woman with subacute dementia].

PMID- 8755364
TI  - [Historical analysis of J.M Charcot's work. The school of Charcot at the
      Salpetriere].

PMID- 8755366
TI  - [How is new selective neuropsychiatry being structured?].

PMID- 8755367
TI  - [Magnetic resonance in cerebral anoxia].

PMID- 8755368
TI  - [The consultation exchange between primary and neurological care].

PMID- 8755369
TI  - [Bilateral infarct in the area of superior cerebellar artery].

PMID- 8755370
TI  - Managed care: emerging issues in clinical ethics.

PMID- 8755371
TI  - What are the best educational models for the professional preparation of
      audiologists?

PMID- 8755372
TI  - Imaging tomorrow. What's ahead for our professions.

PMID- 8755373
TI  - Possibilities of mission impossible: market to survive.

PMID- 8755374
TI  - Have wheels will travel.

PMID- 8755375
TI  - Disyllables as a link between babbling and first words.

PMID- 8755376
TI  - I know the answer, I just didn't recognize the question!

PMID- 8755377
TI  - Medical records and other stories: a narratological framework.
AB  - A new model of the medical record is introduced which can incorporate context,
      structure, process and use of the medical record within a single narratological
      framework. It is claimed that the analysis of narrative and, in particular, the
      study of the story metaphor can provide a theoretical model which provides
      coherence within the broad discipline of Medical Informatics. It is argued that
      this framework maintains different levels of abstraction, is useful for teaching
      and clinical practice, and that its concepts can be readily understood by those
      in both lay and technical healthcare professions.

PMID- 8755378
TI  - The medical record: narration and story as a path through patient data.
AB  - Kay and Purves' proposed narratological model of the medical record is based on
      the familiar phenomenological insight that the perception of data is conditioned
      by the conceptual framework of the perceiver. Unfortunately, unless handled very
      carefully, this approach will make the significance of a medical record unique to
      the person who constructed it and impermeable to outside scrutiny. However, when
      integrated into the analog-model of the medical record, the narratological model
      can be accommodated as the clinician-relative construction of a patient profile
      within the data that make up the medical record. Some implications for the
      construction of expert systems and competence analysis are indicated.

PMID- 8755379
TI  - Is there anything new about the so-called "medical" record?

PMID- 8755380
TI  - The physician's flexible narrative.

PMID- 8755381
TI  - Literature and logbook--art and science.

PMID- 8755382
TI  - Coding clinical information: analysis of clinicians using computerized coding.
AB  - Data are presented of a controlled experiment with a computerized browsing and
      encoding tool. Eighteen practicing clinicians extracted medical concepts from two
      narrative exercise cases using two approaches, traditional and computer-assisted
      use of ICD-9. Our results indicate that by using a computerized coding tool the
      completeness of coding can be improved by up to 55%, that by enforcing mandatory
      as opposed to optional modifier codes results in lower rates of incomplete coding
      (0 and 55%, respectively), higher rates of correct coding (41 to 92%) and no
      change in incorrect code, and that manual coding takes twice as long than coding
      with the help of the computerized coding tool. Clinicians need 59% more time for
      processing the whole set of codes than is suggested by the sum of individual
      codes. We conclude that the use of a computerized coding tool can save time and
      result in higher quality codes. However, the real time spent on coding may be
      underestimated when looking at individual coding times, instead of the whole task
      of processing a clinical scenario.

PMID- 8755383
TI  - Improving coded data entry by an electronic patient record system.
AB  - Data are presented on the use of a browsing and encoding utility to improve coded
      data entry for an electronic patient record system. Traditional and computerized
      discharge summaries were compared: during three phases of coding ICD-9 diagnoses
      phase I, no coding; phase II, manual coding, and phase III, computerized
      semiautomatic coding. Our data indicate that (1) only 50% of all diagnoses in a
      discharge summary are encoded manually; (2) using a computerized browsing and
      encoding utility this percentage may increase by 64%; (3) when forced to encode
      manually, users may "shift" as much as 84% of relevant diagnoses from the
      appropriate coding section to other sections thereby "bypassing" the need to
      encode, this was reduced by up to 41% with the computerized approach, and (4)
      computerized encoding can improve completeness of data encoding, from 46 to 100%.
      We conclude that the use of a computerized browsing and encoding tool can
      increase data quality and the percentage of documented data. Mechanisms bypassing
      the need to code can be avoided.

PMID- 8755384
TI  - Pseudonyms for cancer registries.
AB  - In order to conform to the rigid German legislation on data privacy and security
      we developed a new concept of data flow and data storage for population-based
      cancer registries. A special trusted office generates a pseudonym for each case
      by a cryptographic procedure. This office also handles the notification of cases
      and communicates with the reporting physicians. It passes pseudonymous records to
      the registration office for permanent storage. The registration office links the
      records according to the pseudonyms. Starting from a requirements analysis we
      show how to construct the pseudonyms; we then show that they meet the
      requirements. We discuss how the pseudonyms have to be protected by cryptographic
      and organizational means. A pilot study showed that the proposed procedure gives
      acceptable synonym and homonym error rates. The methods described are not
      restricted to cancer registration and may serve as a model for comparable
      applications in medical informatics.

PMID- 8755385
TI  - Linking patient information systems to bibliographic resources.
AB  - Medical informatics researchers have explored a number of ways to integrate
      medical information resources into patient care systems. Particular attention has
      been given to the integration of on-line bibliographic resources. This paper
      presents an information model which breaks down the integration task into three
      components, each of which answers a question: what is the user's question?, where
      can the answer be found?, and how is the retrieval strategy composed? Twelve
      experimental systems are reviewed and their methods for addressing one or more of
      these questions are described.

PMID- 8755386
TI  - A graph-grammar approach to represent causal, temporal and other contexts in an
      oncological patient record.
AB  - The data of a patient undergoing complex diagnostic and therapeutic procedures do
      not only form a simple chronology of events, but are closely related in many
      ways. Such data contexts include causal or temporal relationships, they express
      inconsistencies and revision processes, or describe patient-specific heuristics.
      The knowledge of data contexts supports the retrospective understanding of the
      medical decision-making process and is a valuable base for further treatment.
      Conventional data models usually neglect the problem of context knowledge, or
      simply use free text which is not processed by the program. In connection with
      the development of the knowledge-based system THEMPO (Therapy Management in
      Pediatric Oncology), which supports therapy and monitoring in pediatric oncology,
      a graph-grammar approach has been used to design and implement a graph-oriented
      patient model which allows the representation of non-trivial (causal, temporal,
      etc.) clinical contexts. For context acquisition a mouse-based tool has been
      developed allowing the physician to specify contexts in a comfortable graphical
      manner. Furthermore, the retrieval of contexts is realized with graphical tools
      as well.

PMID- 8755387
TI  - Attitudes of community pharmacists, university-based pharmacists, and students
      toward on-line information resources.
AB  - The study sought to explore the attitudes of community pharmacists, university
      based pharmacists, and pharmacy students before and after exposure to
      computerized systems of on-line information services. A 42-item attitudinal
      survey was administered to 21 community pharmacists, 7 university clinical
      pharmacist faculty, and 17 senior pharmacy students, prior to and at the end of a
      year of access to Grateful Med and BRS Colleague. Few significant differences
      were noted among the participants at baseline. No significant interaction-effect
      differences for type of participant or system used were found. Participants were
      generally positive about computers in general, the accuracy of on-line
      information services, their impact on knowledge and confidence, and their
      usefulness for pharmacists.

PMID- 8755388
TI  - The road to professionalism in medical informatics: the role of training.

PMID- 8755390
TI  - [Damage to the optic nerve: an animal model].

PMID- 8755391
TI  - [Microsurgical therapy of orbito-apical intracanalicular processes].

PMID- 8755392
TI  - [Surgical therapy of endocrine orbitopathy].

PMID- 8755393
TI  - [Contribution to facial surgery in therapy of orbital tumors].

PMID- 8755394
TI  - [Abnormalities of the orbital area].

PMID- 8755395
TI  - [Therapy of orbital fractures].

PMID- 8755396
TI  - [Infection of the orbits from the oromandibular surgery viewpoint].

PMID- 8755397
TI  - [Rhinosurgery in diseases of the orbits].
AB  - The rhinosurgical procedures in different orbital diseases are discussed. Special
      attention is directed to the application of endoscopic and microsurgical
      techniques. We describe the different stages of orbital involvement in 106
      patients. Computer-tomography has proven to be most effective informing the
      extent of sinus disease as well as orbital inflammation, because of this an
      immediate stage-dependent therapy can be commenced. Indications for endonasal,
      extranasal or for combined approaches are given. In two patients with blindness
      due to mycosis we performed an exenteration of the orbit. The advantages of
      extranasal and endonasal techniques for decompression of the orbit are discussed.
      Successful approaches for the extranasal microsurgical removal of orbital tumors
      are described. The results demonstrate that the surgically decompressed optic
      nerve has a favourable prognosis. Pathogenesis, diagnostic procedures,
      indications and microsurgical techniques of the traumatized optic nerve are
      discussed. The long-term follow up results of our optic nerve decompression cases
      are presented.

PMID- 8755398
TI  - [Computer-assisted documentation of mandibular fractures].
AB  - For the registration, documentation and evaluation of patient data in cranio
      maxillo-facial (cmf) trauma surgery a Windows-based application front end for
      relational data base systems (RDBS) has been developed. A simple-to-learn, easily
      reconfigurable user interface can be adjusted to the dynamically changing needs
      of individual departments. A graphical user interface (GUI) eases the entry of
      complex information like fracture positions, the location of implanted
      osteosynthesis material, etc. The new program also simplifies the daily routine
      documentation tasks. Being linked to a Hospital Information System (HIS) it makes
      use of the patients' individual base data stored there. Statistical data for
      various studies can be extracted from the database. The program has been
      successfully tested on a collective of 1.178 cmf trauma patients. Predefined
      analyses can be generated now by the simple click of a button for various case
      selections. New users learn to operate the program in a very short time.

PMID- 8755399
TI  - [Value of magnified panorama image for diagnosis of fractures of the central
      mandibular segment].
AB  - The accuracy of sonographic imaging of displaced mandibular fractures has been
      investigated experimentally. Mandibles taken from fresh pig cadavers have been
      osteotomized and fracture displacement according to the three types of
      dislocation has been performed. The bony fragments were connected by threads to
      enable reproducible ranges of displacement. The investigations were performed
      with 7.5, 10 and 13 MHz linear arrays. Longitudinal and lateral displacements
      from 1 to 10 mm and axial displacements from 1 degree to 5 degrees were
      investigated. We could find, that B-mode-sonography is very sensitive to detect
      the direction of displacement in mandibular fractures, if at least 1 mm of
      displacement exists. The measurements of the amount of displacement show, that
      the difference of the sonographic measurements and the real existing displacement
      depends on the direction of the displacement and the chosen frequency of
      examination. It is independent from the amount of displacement. The mean error of
      all examination is less than 0.4 mm. The greatest difference between the real
      displacement and the measured one is found in axial displacement from 1 degree to
      3 degrees. The results show, that B-mode sonography is a reliable method
      detecting displaced fractures of the mandible and the clinical application of the
      method can be recommended. The sonographic detection of nondisplaced fractures is
      a problem which needs further technical development.

PMID- 8755400
TI  - [AO and miniplate osteosynthesis of the mandible in an 8-year comparison].
AB  - During a period of 8 years (1986-1994) we treated 183 patients with mandibular
      fractures. Within this period we changed our treatment protocol from the rigid
      internal fixation (AO/ASIF method) to monocortical noncompression miniplates. The
      complications of 127 AO/ASIF cases versus 41 miniplate cases were studied.
      Complications mostly consisted in dehiscences. Comparing the two methods we found
      more complications (19.5%) when the AO plate is applicated via an intraoral
      approach. After extraoral AO treatment and after monocortical miniplates there
      was no significant difference concerning our complications (8.1% versus 7.3%).

PMID- 8755401
TI  - [Is miniplate osteosynthesis for combined mandibular body and bilateral
      mandibular condyle fractures adequate?].
AB  - Between 1980 and 1993 81 patients with a combined mandibular body and bilateral
      mandibular condyle fractures underwent open reduction and internal fixation of
      the mandibular body. The following methods were used: 29 x miniplate
      osteosynthesis, 28 x maxiplate osteosynthesis, 13 x lag screws, 10 x combinations
      and once titanium mesh. Reoperations because of occlusal disturbances were
      necessary in two cases of miniplate fixation, in one case of maxiplate fixation
      and in one case of lag screw fixation. In 1994 28 patients were reviewed.
      Posterior crossbite as operative sequela was noted in 2 (out of 14) patients
      after miniplate osteosynthesis, in 3 (out of 9) patients with maxiplate
      osteosynthesis, in 1 (out of 4) patients with combined miniplate and lag screw
      fixation and in 0 (out of 3) cases with lag screws. In cases of oblique
      mandibular body fractures we recommend the lag screw technique. Maxiplate
      osteosynthesis is more troublesome and more difficult in comparison with
      miniplate osteosynthesis. Therefore we recommend the miniplate osteosynthesis for
      the remaining types of mandibular body fracture and if needed the mandibular
      condyle.

PMID- 8755402
TI  - [Treatment outcome and complications of surgical and conservative management of
      mandibular fractures].
AB  - Retrospective analysis of 712 patients with 1166 mandibular fractures and follow
      up-study of 374 patients with 593 fractures was performed for discrimination of
      differences in wound- and bone-healing as well as late results between operative
      and conservative fracture treatment. 46.1% (328) of all patients have been
      treated conservatively, 53.9% (384) have been treated by operation. The follow up
      was performed on 255 patients with operative fracture treatment and 119 patients
      with conservative treatment. In 3.0% of the operatively treated patients
      bacterial infections occurred, in comparison to 8.7% of conservatively treated
      patients. From the viewpoint of functional aspects, such as occlusion,
      articulation and mandibular movement as well as radiological signs in the
      fractured region patients after operative treatment have shown partly
      significantly better results during the follow up compared to the group of
      conservatively treated patients. Neurological testings of inferior alveolar nerve
      and mental nerve have shown significantly better results in the group of
      conservatively treated patients. Since the functional results are much better
      after operative treatment, osteosynthesis with miniplates should be performed if
      there are no contraindications. The more precise reconstruction and stabilization
      of the fragments shortens time of hospitalization and leads to sooner
      functionality of the mandible.

PMID- 8755403
TI  - [Treatment of mandibular fractures with different fixation techniques--results of
      a prospective fracture study].
AB  - In a prospective study 150 adult patients with mandible fractures were analysed.
      Criteria for entry into the study were fractures of the mandibular body with and
      without associated condylar fractures. The fractures must fit to the Spiessl
      classes F1 and F2, L1 to L4, W0 to W3 and the patients must have had a sufficient
      dentition to judge their occlusion. Not included were patients with combinations
      of mandible and Le Fort fractures, comminuted and defect fractures and patients
      who could not communicate preoperatively in order to have a full preoperative
      examination. The patients were equally distributed among 3 different treatment
      groups. Group 1 was treated conservatively with MMF, only displaced fractures
      which needed open reduction were internally fixed with wire osteosynthesis. Group
      2 received rigid internal fixation with AO 2.7-plates from an intraoral approach,
      group 3 internal fixation with miniadaption-plates also from an intraoral
      approach. Using a standardized treatment protocol the patients were followed in
      defined intervals up to a maximum of 2 years after therapy. Group 1 presented
      with the lowest complication rate, group 2 with the highest rate of overall
      complications as far as disturbances of the occlusion and sensory disturbances
      were concerned. Except one plate fracture in group 3 with subsequent
      pseudarthrosis, which required a reosteosynthesis with a rigid plate, no major
      complications in bone healing were observed.

PMID- 8755404
TI  - [Differential indications for various therapeutic osteosynthesis concepts in
      mandibular fractures].
AB  - The surgical treatment of different types of mandibular fractures requires
      complex consideration. It can be realised not by the application of only one
      treatment concept, e.g. miniplates or rigid osteosynthesis, but a differentiated
      indication of every stability system depending on the individual requirements in
      each case. Basing on the results of clinical studies the contemporary concept
      applied at Munster in treatment of mandibular fractures is presented.

PMID- 8755405
TI  - [Late outcome and complications of mandibular compression osteosynthesis with
      intraoral approach--a 10-year study].
AB  - Late results and complications following rigid internal fixation of mandibular
      fractures-a 10 year survey. From 1984 to 1993 541 fractures of the mandible in
      332 patients have been treated by rigid internal fixation with the mandibular
      compression system (MCS). In 0.8% we saw serious complications like
      pseudarthrosis or osteomyelitis. In a retrospective study 105 patients with 171
      fractures of the mandible could be examined 4.1 years after osteosynthesis. In
      case of preoperative normesthesia of the inferior alveolar nerve in 74.1% of the
      fractures nomesthesia was still present, 18.1% of the fractures showed
      hypesthesia and 4.2% showed complete anesthesia. In case of already
      preoperatively existent hypesthesia in 81.8% of the fractures normesthesia and in
      8.2% hyp- or paresthesia were seen. There were no anesthesias seen in this group.
      3.6% of the fractures showed mild occlusal disharmonies.

PMID- 8755406
TI  - [Results of compression osteosynthesis with intraoral approach in 922 mandibular
      fractures].
AB  - A series of 922 fractures of the mandibular body (median-paramedian, horizontal
      ramus and mandibular angle) was treated within a 10 years period from January
      1984 to December 1993 by an uniform treatment method. It consisted of compression
      plating with bicortical screw anchorage and intraoral approach, thus avoiding any
      outer scar and facial nerve damage. Postoperatively intermaxillary fixation was
      not used in any of these cases. A solid bony union was achieved in more than 99%
      of the cases. Major complications as osteomyelitis and non union were observed in
      8 cases (0.86%). Minor complications of soft tissue infections without
      interference of fracture healing as haematomas, soft tissue abscesses and suture
      dehiscence were observed in 6.1%. A separate analysis of 352 mandibular angle
      fractures, which are regarded as particularly problematic, showed a frequency of
      severe complications (osteomyelitis and nonunion) of 0.85%. This is comparable
      with the frequency of complications of 0.86% within the total series. In this
      largest series of compression plating via intraoral approach, which has ever been
      published, the technique again has proved its significance as a standard
      procedure for the treatment of mandibular fractures.

PMID- 8755407
TI  - [Surgical reposition and fixation of mandibular condyle fractures via intraoral
      approach].
AB  - In a case series 54 patients with 61 subcondylar fractures had been treated by
      surgical repositioning and miniplate-fixation by an intraoral approach.
      Functional results with special regard to the function of the temporomandibular
      joint TMJ were registered not earlier than 1 year postoperatively and compared to
      a case series of 48 patients with 63 conservatively treated subcondylar
      fractures. Axiographic or pantographic investigation proved higher incidence of
      TMJ-disorders as it was the case for the common clinical functional examination.
      TMJ-function was worse in the conservatively treated cases especially in
      dislocated fractures. Therefore dislocated fractures especially with luxation of
      the TMJ should be surgically treated. Surgical repositioning and fixation by an
      intraoral approach is difficult and allows only limited access and view of the
      fracture, but avoids complications by scaring or facial nerve damage and seems to
      be sufficient for adequate repositioning. Minor dislocations showed no influence
      on TMJ-function. Of course surgical repair of disrupted TMJ-ligaments is not
      possible by an intraoral approach-disrupted TMJ-ligaments in luxated joints seem
      to be of major importance for the later TMJ-function.

PMID- 8755408
TI  - [Experiences with the 3-D miniplate osteosynthesis in mandibular fractures].
AB  - A geometrically closed quadrangular plate secured with bone screws creates
      stability in three dimensions. The smallest structural component of a 3-D-plate
      is an open cube or a square stone. Our clinical results and biomechanical
      investigations have shown a good stability of the 3-D-plates in the
      osteosynthesis of mandibular fractures without major complications. The thin 1.0
      mm connecting arms of the plate allow easy adaptation to the bone without
      distortion. The free areas between the arms permit good blood supply to the bone.

PMID- 8755409
TI  - [2.7 mm (AO) or 2.0 mm miniplate osteosynthesis in mandibular fractures].
AB  - In a retrospective study on 302 patients, miniplate osteosynthesis (n = 236) and
      rigid internal fixation (n = 66) in patients with fractures of the mandible were
      investigated. The total complication rate following miniplate osteosynthesis was
      6.5% compared to 12.7% following rigid internal fixation. Additional
      intermaxillary immobilisation did not avoid postoperative complications. In
      patients with multiple or comminuted fractures of the mandible, rigid internal
      fixation demonstrated a lower complication rate compared to miniplate
      osteosynthesis.

PMID- 8755410
TI  - [Long-term outcome after intraoral miniplate osteosynthesis in mandibular angle
      fractures].
AB  - The success or failure of intraoral miniplate osteosynthesis is mainly influenced
      by right indication. More than 90% of the fractures of the mandible were treated
      successfully by intraoral noncompressive miniplate osteosynthesis. Hence a
      postoperative intermaxillar fixation seems not to be necessary. Considering the
      range of indication this is an effective method of no complications. Nevertheless
      an immobilisation for one week is accepted by our patients without any problems
      and is recommended according to normal healing. The collective of our patients in
      Essen is selected as unilateral multiple fractures, comminuted fractures and
      infected fractures of the mandible were not treated by miniplate osteosynthesis.

PMID- 8755411
TI  - [Functional stability of Champy miniplate osteosynthesis in mandibular angle
      fractures].
AB  - This paper presents the results of the treatment of fractures of the mandibular
      angle using miniplate osteosynthesis. From 1984 to 1993 347 patients with 358
      fractures were operated in the department of Maxillofacial Surgery at the
      University of Cologne. In all cases total bone healing could be observed while
      complications were rare.

PMID- 8755412
TI  - [Experiences and results in management of mandibular fractures with the modified
      Krenkel lag screw--a retrospective study].
AB  - The stable osteosynthesis of mandibular fractures with the modified lag screw
      (Krenkel) has proven superior to conventional lag screws in theoretical models
      and clinical use. Compared to osteosynthesis with plate systems, the lag screw
      technique is more difficult to learn for the unexperienced, but the reduction of
      fragments under compression with a lag screw and the stabilisation of lower jaw
      rotation with an additional short miniplate in our experience has proven
      successful in clinical use.

PMID- 8755413
TI  - [Lag screw osteosynthesis in median mandibular fractures--technique and outcome].
AB  - The lag screw technique for treatment of simple median and paramedian fractures
      of the mandible is reemphasized. Major advantages over bone-plate fixation are
      the rapid application since adapting and bending of a bone plate is obviated as
      well as the lower costs of the osteosynthesis material. A review of 12 patients
      with fractures of the anterior mandible who had lag screws placed for fracture
      treatment showed that it is a successful method of providing rigid internal
      fixation associated with a low postsurgical complication rate.

PMID- 8755415
TI  - [Mandibular fractures due to implant management--incidence, mechanism of injury
      and therapeutic characteristics].
AB  - We report of 5 of 337 patients (1.48%), in whom a fracture of the edentulous
      atrophied mandible occurred after dental implants had been inserted. In 79
      patients a sandwich osteotomy (anterior and/or lateral mandible) had been carried
      out together with the insertion of implants. The reason for a fracture was
      infection in 3 patients and weakening of the atrophied mandible by the additional
      osteotomies in 2 patients. One of the latter two was seen intraoperatively and
      fixed immediately using miniplates. The other occurred about 4 weeks
      postoperatively and was not discovered until callus had been developed.
      Consequently only 4 of the 5 patients were treated by osteosynthesis. In two
      patients no implants were lost. The application of bone morphogenetic protein
      (BMP) helped to avoid the loss of implants because it accelerated ossification of
      the fracture and the integration of the implants.

PMID- 8755414
TI  - [Single lag screw osteosynthesis for management of mandibular angle fractures].
AB  - 80 patients with 83 fractures of the mandibular angle were treated by lag screw
      fixation. The screws were placed through a transoral incision with transbuccal
      trochar instrumentation. No maxillomandibular fixation was used. Complications
      occurred in 12 fractures (14%), of which 5 (6%) required secondary surgical
      intervention. In all cases bony union was achieved 6 months postoperatively.
      Indications and advantages of the technique are discussed.

PMID- 8755416
TI  - [Incidence and regeneration time of disorders of the inferior alveolar nerve in
      osteosynthesis of mandibular fractures--a prospective clinical study].
AB  - In a prospective study posttraumatic and postoperative sensitivity disturbances
      after mandible fractures in the region of osseous course of the inferioralveolar
      nerve were assessed. The study contains 28 patients with 31 mandible fractures.
      For assessment somato sensoric evoked potentials and computer assisted pain and
      thermal sensitivity testing was used. A rate of 32% posttraumatic and 52% nerve
      disturbances resulting from osteosynthesis was found. In 81% the sensitivity
      disturbances lasted only 6 months post-operatively. In 19%, mainly cases of
      fracture dislocation of 5 mm minimum, anesthesia and hypesthesia lasted for more
      than half a year.

PMID- 8755417
TI  - [Position of the disc in collum mandibulae fractures--a magnetic resonance
      tomography study].
AB  - 39 condylar mandibular fractures were examined by magnetic resonance imaging
      (MRI) within the first 12 hours after trauma prior to therapy. A new
      classification has been applied on the traumatic disc displacements. Three types
      A, B, C can be distinguished. Type A means no displacement in relation to the
      condylar fragment and the fossa. Type B means a displacement in the transversal
      plane exceeding the physiologic range of movement. Type C means displacement in
      the sagittal as well as in the transversal plane which exceeds the physiologic
      range of movement of the disc. The classified type of displacement could not be
      correlated exactly with dislocation and position of the bony fragments. Therefore
      the type of displacement cannot be predicted from conventional radiographs. Three
      cases of evident rupture of the disc in the biconcave zone could be shown by MRI.
      This kind of displacement has not been represented in the classification yet. In
      a presented case a rupture of the disc had been depicted preoperatively and the
      disc could be repaired via an preauricular approach. By means of MRI surgeons in
      future are able to pay more attention to the traumatology and reconstructive
      surgery of the temporomandibular disc.

PMID- 8755418
TI  - [Nuclear magnetic resonance tomography study of the position of the discus
      articularis after dislocation fractures].
AB  - 16 patients with a total of 25 condyle neck fractures, of which 17 were fractures
      with luxation, 4 fractures with dislocation and 4 diacapitular fractures, were
      checked clinically and using x-ray and nuclear magnetic resonance diagnosis.
      Except for the diacapitular fractures, all fractures were treated surgically and
      fixed functionally stable using mini plates or lag screw osteosyntheses. The
      examination results show that in the majority of cases a regular discus position
      and joint function appears along with the repositioning of the condyle neck.

PMID- 8755419
TI  - [Mandibular collum fracture in the ultrasound image--indications and limits from
      the viewpoint of 3 years imaging experiences].
AB  - The Ultrasound technique as an image producing procedure for fractures of the
      mandibular collum is outlined with physical theory and clinical examples.
      Advantages and disadvantages are compared and it is stated that a part of all
      patients with fractures might have a benefit from this method. Mentally
      handicapped patients, pregnant women and all sorts of fidgety patients will
      profit by the ultrasound investigation as the only way to ascertain the bone
      fracture. There is necessity to relate the sonogram to a conventional X-ray
      picture whenever it is possible, for the procedure is suited to prove the
      fracture, not to exclude it.

PMID- 8755420
TI  - [Indications for various reconstruction and osteosynthesis methods in surgical
      management of subcondylar fractures of the mandible].
AB  - We do not advocate routine open reduction in subcondylar fractures, but there are
      some indications for surgical treatments. If we have decided for open reduction,
      the risks must be weighed against the benefits. If we are not sure, that the
      condyle is in a correct position, we avoid rigid internal fixation and we prefer
      only a temporary stabilization with resorbable Polydioxanone, Polylactide or
      autologous bone-pins. In non oblique fractures, we recommend only open reduction
      without further internal fixation. The advantage is that the condyle has the
      ability to move into a physiologic position and there is no need to remove metal
      implants in a second operation, the disadvantage is that we cannot avoid MMF and
      functional therapy, but our experience shows that the functional therapy can be
      shortened. Resorbable- and bone-pins could not take place of miniplates or
      traction-screws, but in selected cases, they could enlarge the surgical treatment
      in subcondylar fractures.

PMID- 8755421
TI  - [Conservative versus surgical therapy of unilateral fractures of the collum
      mandibulae--anatomic and functional results with special reference to computer
      assisted 3-dimensional axiographic registration of condylar paths].
AB  - A clinical, radiographic and computer-assisted axiographic follow-up was carried
      out on 60 patients who had been treated for unilateral subcondylar fractures.
      These were patients of the Department of oral, maxillofacial and facial plastic
      surgery of the Medical Faculty of the University of Technology in Aachen,
      Germany. After surgical reduction of the condyle with fixation by osteosynthesis
      where results were positive, 27 patients exhibited a shortening of the condyle
      paths on the side operated on by up to 16.4%. Although conservative therapy
      produced slighter straightening of the condyle with more or less strongly marked
      condylar deformations in two-thirds of the cases, functionally more positive
      results were obtained by markedly slighter limitation of the condyle paths on the
      traumatized side. These results would appear to indicate operative therapy of
      unilateral subcondylar fractures in the case of luxation fractures, condylar
      dislocation in excess of 50 degrees, and in those cases where intermaxillary
      immobilization is not feasible. In the remaining cases, conservative treatment is
      preferred, due to it showing functionally more positive results.

PMID- 8755422
TI  - [Late results of 15 years and longer after mandibular condyle fractures].
AB  - A sample of 91 patients who had suffered from condylar fractures in the years
      1970-1977 could be followed up. The mean follow up period was 19.8 years. As a
      prognostic relevant parameter the patient's age at the time of the accident as
      well as the type of the fracture where taken into account. Clinically young (8-11
      years at the time of the accident) patient's with no or low grade dislocation
      showed the best results. Almost 36% of the patients with high grade dislocation
      or luxation presented measurable pathological changes during function. The
      condylar movement was assessed by using 3D-optoelectronic measurement. Despite
      severe radiographic alterations and hindered condylar translation in cases with
      high grade dislocation or luxation, mouth opening was not restricted in the
      majority of the patients. It seems that the lack of condylar translation is
      compensated by extensive rotation.

PMID- 8755423
TI  - [Comparison of miniplate and lag screw osteosynthesis in treatment of collum
      fractures].
AB  - The question whether- and if by which means-operative reconstruction of condylar
      process fractures is appropriate is still unresolved. This study was initiated to
      compare osteosynthesis of low dislocated and/or luxated condylar fractures by
      means of miniplates or lag screws according to Eckelt. 22 patients participated,
      16 being treated with miniplate osteosynthesis, 6 with lag screws. Investigation
      concentrated on the parameters TMJ-function (side shift in dynamic and static
      occlusion, maximum interincisal distance, impairment of pro- and laterotrusion),
      radiologic post-operative fragment position, intra- and postoperative
      complications, and evaluation by the patients. Miniplate osteosynthesis showed
      better results leading in 80% to an unimpaired TMJ function compared to 50% of
      the lag screw group. Miniplate osteosynthesis was performed faster. No intra- or
      postoperative problems occurred in contrary to the lag screw, where one fracture
      of the screw intra- and one post-operatively were noted. Even if the numbers are
      too small for statistical calculations, trends are shown favouring miniplate
      osteosynthesis for operative reconstruction of condylar fractures.

PMID- 8755424
TI  - [Miniplate osteosynthesis of mandibular fracture in local anesthesia--indications
      and outcome in 316 patients].
AB  - In an retrospective analysis of 316 patients with mandibular fractures treated
      between 1984 and 1993 at the maxillo-facial surgery of university of Cologne
      could be shown that the application of miniplate in local anesthesia causes no
      more complication than in general anesthesia. We would therefore recommend this
      technique for not to complicated cases of isolated or double fractures of the
      mandible. In cases of obstacles to general anesthesia it may be favoured even in
      severe cases.

PMID- 8755425
TI  - [Transoral miniplate osteosynthesis of mandibular condyle fractures--optimizing
      the surgical method].
AB  - Under certain conditions dislocated low subcondylar fractures of the mandible can
      be reset by intraoral approach and treated using miniplate osteosynthesis. This
      approach protects the facial skin as well as Ramus marginalis. Over a period of
      30 months, the authors performed this surgery on 34 patients with dislocated low
      subcondylar fractures of the mandible. This approach requires a 90 degree drill
      and screw device, a special resetting hook and retractors. The surgery is
      performed preferably under endoscopic viewing conditions. The results show that
      transoral miniplate osteosynthesis is technically feasible, representing a
      recommended therapy considering the particular indication and requiring the
      equipment specified above.

PMID- 8755426
TI  - [Results of follow-up of temporomandibular joint fractures in 30 children].
AB  - Disturbances of facial growth and occlusion as well as temporomandibular joint
      dysfunction are possible sequelae of temporomandibular joint fractures in
      children. In a follow-up study we examined 30 children with conservatively
      treated condylar fractures of the mandible (age at time of accident from 9 months
      to 13 years) regarding dysfunction or growth disturbances within the
      stomatognathic system. The mean interval between the accident and the follow-up
      was 4 years and 11 months. We found 6 cases with tilted occlusional planes in the
      'en face' analysis, 3 of them with bilateral condylar fractures. There was only
      one case with a facial asymmetry. The interincisive distance was never below 35
      mm. Only 3 patients, all of them with bilateral condylar fractures, had a
      restricted mobility of the mandible. Remodelling of the condylar head was good in
      92% of the cases. Two patients with bilateral fractures showed formation of a
      bifid condyle without ankylosis. Deviation of the ascending ramus in the
      horizontal plane was observed radiographically in 21% of the cases with
      unilateral fractures and in 33% with bilateral fractures respectively and always
      in a medial direction. Measurement of the length of the Processus articularis in
      the orthopantomogramm showed a shortening in 70% of the cases on the fracture
      side. The radiographic evaluation of facial asymmetry after Ricketts and Mulick
      only revealed an angle difference of more than 5 degrees in some cases.

PMID- 8755427
TI  - [Neurologic examinations for facial nerve damage in surgically treated mandibular
      collum fractures].
AB  - Transcranial magnetic stimulation is a new method for objective evaluation of the
      facial nerve without constraints for the patient. By the first time, especially
      cortical lesions can be detected objectively. Using this method, a permanent
      disturbance of the ramus marginalis mandibularis after operative treatment of
      fractures of the mandibular condyle could be certainly excluded. Therefore,
      because of the clear presentation and the possibility of enlargement, the deep
      submandibular approach, using a correct operative technique, can be strictly
      recommended.

PMID- 8755428
TI  - [Fractures of the mandibular collum in childhood--a long-term follow-up with
      orthopantomography].
AB  - The study including fifty children younger than 10-years-old with dislocated
      unilateral collum fractures concerns the chronological development of
      morphological alterations in the orthopantomogramm. Regardless of fracture type,
      the radiographs indicate, that a very good restitution can be attained with an
      exclusive functional therapy using an activator in all analyzed patients. A
      realignment can not be found.

PMID- 8755429
TI  - [Mandibular micrognathism as a sequela of early childhood capitulum fractures and
      their treatment using distraction osteogenesis].
AB  - We report about our experience in five patients who suffered from a mandibular
      micrognathia after ancylosis of the temporomandibular joint. At first the
      ancylosis was removed using a costochondral graft. About one year later, the
      mandible was cut by an osteotomy behind the last visible toothbud and a
      distractor was inserted. The mandible was to a slide overcorrection. This has to
      be taken into account to compensate a certain relapse. At first we used an
      unidirectional device, for one and a half years we have used a bidirectional
      device (Normed from Tuttlingen/Germany) which enables us to correct mandibular
      hypoplasias more adequately. Up to now our experience shows, that gradual callus
      distraction leads to stable normalization of mandibular hypoplasias. Functional
      problems concerning chewing and speech are solved, the dramatical improvement of
      the profile of the face may avoid psycho-social problems for these patients.

PMID- 8755430
TI  - [Fractures of the atrophic mandible--a challenge for therapy].
AB  - Because treatment of fractures of the atrophic mandible still today presents
      significant difficulties and treatment modalities remain controversial, 87 of
      these consecutive fractures which were treated by an uniform method as
      compression osteosynthesis were evaluated. A new classification of the degree of
      atrophy which considers the special interest of fracture treatment is introduced.
      It is based on a metrical measurement of the height of the mandible in the
      fracture area. Mandibles of 16 to 20 mm height are classified as class I atrophy,
      those of 11 to 15 mm as class II atrophy, and those with a height of 10 mm or
      less as extremely atrophic mandibles or class III atrophy. This simple and
      reliable classification could also be used in future investigations on the
      results of different treatment modalities in atrophic mandibles. In our series of
      87 fractures of the atrophic mandible which were treated by compression
      osteosynthesis 97% resulted in a solid osseous union without the need of a second
      surgical intervention. Three major complications occurred: 1 osteomyelitis and 2
      non-unions (the latter in one patient with a double fracture of a class III
      atrophy mandible). To the best of our knowledge this series is the largest of
      fractures of truly atrophic mandibles treated by one uniform method. Compared to
      other treatment modalities compression osteosynthesis produced acceptable results
      and is recommended as the treatment of choice in fractures of the atrophic
      mandible.

PMID- 8755431
TI  - [War injuries of the mandible and sequelae 50 years later].
AB  - About 50 years after the end of World War II 84 former soldiers of the German
      army were examined for aftereffects of their war injuries. Among the data
      recorded for analysis were the age at which the injury was incurred, the
      examination intervals, the region affected by the injury and the cause of the
      injury, but also the different levels of aftereffects of injuries. A total of 53
      applicants had suffered mandibular injuries. Considering the wide scattering
      range, it can be concluded that values of about 20 percent represent a mean
      degree of incapacitation, primarily due to a combination of loss of teeth and
      parts of the alveolar process and the effects on the prosthetic support.
      Casuistic examples illustrate special histories or developments including
      sarcomagenesis in the region originally affected by the injury.

PMID- 8755432
TI  - [Therapeutic concept in comminuted and defect fractures of the mandible].
AB  - Immediate live-saving emergency treatment of patients with heavily communited and
      partially defective mandibles by airway intubation, control of haemorhage and
      primary treatment of wounds necessarily must be followed by a staged concept of
      treatment for the functional and aesthetic rehabilitation of hard and soft tissue
      in order to enable the patient to survive not only biologically but also
      socially. Out of 384 patients with surgically treated mandibular fractures, 120
      had multiple fractures, 24 heavily comminuted fractures and 6 sustained vast
      defects. All multiple and communited fractures could be treated successfully by
      an intraoral approach using function-orientated miniplate-osteosynthesis and in
      30 cases functionally stable plates. In patients having sustained vast avulsions
      of soft and hard tissue, immediate emergency-revascularisation was well to the
      fore. In cases of tissue destruction, primarily the position of the jaw stumps
      was secured by plates and reconstruction was done in the early secondary stage
      using composed microvascularly transferred scapular flaps.

PMID- 8755433
TI  - [Gunshot injuries of the mandible].
AB  - 43 patients with gunshot wounds of the mandible were treated in Tubingen and
      Basel between 1968 and 1995. Among them were 31 patients ( = 72.09%) with bone
      loss and defect fractures. Over that time period the treatment principles of
      gunshot wounds have not changed. They are based on an early soft tissue closure
      and an approach from the inside to the outside. Besides that modern techniques in
      maxillofacial reconstructive surgery, which include the application of
      biocompatible plates and screws and the introduction of microvascular
      reconstructive techniques, have enlarged the therapeutical options. Every patient
      needs an individual approach to his special medical condition, which is
      illustrated in three exemplary cases. The combination of the above mentioned
      modern reconstructive techniques prevents long and multiple hospital stays and
      invalidity. Furthermore it is the basis for social reintegration as well as
      functional and esthetic rehabilitation.

PMID- 8755434
TI  - [Experimental studies of the biomechanical stability of different miniplate
      configurations for the mandibular angle].
AB  - Miniplate fixation of mandibular fractures has become the treatment of choice in
      most cases. In fractures of the mandibular angle one 4- or 6-hole miniplate is
      applied ventral to the oblique line of the buccal cortex of the mandible. Not in
      every case adequate stabilization is being accomplished by one plate. In order to
      find out if stability might be increased by a two miniplate fixation technique in
      which a second plate is applied at the inferior border of the mandibular angle 16
      polyurethane and 16 humane mandibles were used and standardized osteotomies were
      performed at the right mandibular angle. These two groups were divided in 4 sub
      groups of four mandibles each and plate fixation of the sub-groups was performed
      as follows: 6-hole plate on the buccal side of the oblique line, 6-hole plate as
      before and an additional 2-hole plate at the inferior margin of the mandible, 2
      hole plate at the oblique line and 6-hole at the inferior margin and finally two
      4-hole plates at the same position. The stability of fixation was measured
      according to Kroon's method (Kroon et al. 1988), based on a three-dimensional in
      vitro model in which muscle forces during mastication acting on the mandible were
      simulated. Axial loading forces close to the fracture site produced significantly
      inferior splaying and lingual compression in single miniplated angle fractures.
      Application of a second miniplate at the inferior border provided significantly
      higher resistance to loading forces close to the fracture line where two 4-hole
      miniplates showed superior results. We conclude that two miniplates are an
      effective method of treating mandibular angle fractures with minor fracture
      surfaces by establishing a second line of osteosynthesis to neutralize rotational
      forces.

PMID- 8755435
TI  - [Therapy of infected mandibular fractures].
AB  - In a follow-up study the results after rigid internal fixation (RIF) in 23
      patients with mandible fractures showing signs of bone infection at the fracture
      sites are presented. Depending on the bony defect RIF was performed with or
      without additional autogenous bone grafts. RIF led to a calculable and uneventful
      bone healing despite the infections. The plates must be fixed with at least 3
      screws on each fracture site and outside the infected areas. An adequate soft
      tissue coverage is a prerequisite for primary or secondary bone transplantation.
      In our series infected fractures were usually observed in problem patients as
      alcoholics, drug addicts or uncooperative patients as mentally disabled or aged
      persons. These patients also frequently escape from the follow-up program. To
      prevent complications an osteosynthesis in problem patients should be performed
      with enough stability so no compliance is required.

PMID- 8755436
TI  - [Development of a mandibular model for evaluating and optimizing the design of
      osteosynthesis materials using finite element analysis].
AB  - The present study was designed to investigate biomechanical and clinical changes
      in the mandibular complex by means of finite element analysis. An analytical
      model developed from human native mandibles was used for this model, CT image
      data were transferred to a computer, and an edge extraction program generated the
      cross-section of bone by specifying a range of CT values for each slice. Pixel
      data from the CT scan were converted into a vector of points (x, y, z) which can
      specify the boundaries of bone. Lateral surfaces are defined by stacking up the
      slices and making use of the vectorized data. The constructed model was used as
      input data for the finite element analysis. The models were solved for stresses
      and forces. The highest principal stresses occurred at the bite point, anterior
      aspects of the coronoid processes, symphyseal region, and right and left sides of
      the mandibular corpus. For further investigation muscular structures have to be
      integrated to establish a model, which can be analysed under multivariate
      aspects.

PMID- 8755437
TI  - [Thermographic quantification of sensory and sympathetic nerve lesions in
      mandibular fractures--a prognostic criterium?].
AB  - As a rule, damage to segmental afferent nerves by trauma is accompanied with
      local impairment of sympathic functions. Standardized quantification of
      subjective items concerning the deficit of sensibility is quite problematical.
      Investigation by electrophysiological means yield not more than qualitative
      issues. In contrast, changes of sympathetic status and reaction of dependent
      dermatomas are quantitatively measurable by thermography. -26 patients with
      unilateral mandibular fractures complained of different posttraumatic or
      postoperative sensible impairment of the third branch of the trigeminal nerve. In
      the course of onto 3 years area and quality of the concerned neural defect were
      correlated to skin temperature that was measured by contact thermography and
      compared to the opposite reference region.- In all cases the early posttraumatic
      period showed a difference in temperature of the corresponding skin areas (delta
      T = 0.43 +/- 0.24 C). In 20 of 26 cases a relation between the changes of
      temperature concerning time and area and the sensible improvement could be seen.
      There was an individual time-lag between these developments. Side-comparing
      thermography was able to forecast improvement in 17 of 26 cases. Thus, the issued
      device provides statements about the amount and the course of posttraumatic loss
      of sensibility.

PMID- 8755438
TI  - Nurse-guided sensitive research in pediatric oncology.

PMID- 8755439
TI  - A pediatric nurse working with children with cancer.

PMID- 8755440
TI  - Children with cancer: the pain experience away from the health care setting.
AB  - Relatively little is known about the nature of pain in children with cancer away
      from the health care setting. Accordingly, this pilot study focused on the pain
      experience in this group. A purposive sample of 20 children, ages 4 through 16
      years, with any type of cancer, was obtained. A semistructured interview
      including the Poker Chip Tool and Preschool Body Outline (ages 4 to 7 years) or
      the Adolescent Pediatric Pain Tool (age 8 to 16 years) was administered to all
      the children once during a clinic appointment. Supplemental parental input was
      sought during the interview. Two of the children also were contacted every 2
      weeks for 3 months. Content analysis indicated that the children experienced pain
      in a number of locations, most frequently the "stomach", joints, legs, and back.
      Pain intensity varied widely. The source of pain identified most often was
      chemotherapy. The most common pain management strategies mentioned were
      rest/sleep, analgesics, rubbing, distraction, social support, and heat. Clearly,
      children with cancer away from the health care setting do have pain. Assessment
      of pain in children with cancer regardless of setting is a necessity.

PMID- 8755441
TI  - Decision making and risk behaviors of cancer-surviving adolescents and their
      peers.
AB  - The specific aims of this descriptive, comparative study were (1) to compare the
      decision-making quality and prevalence of risk behaviors (smoking, alcohol
      consumption, and illicit drug use) between 52 cancer-surviving adolescents and
      their peers; (2) to compare the relationship of decision-making quality and risk
      behavior prevalence in a subset of survivors who had a history of therapy with
      cognitive threat due to late effects of treatment to those without cognitive
      threat; and (3) to test the hypothesis that the higher the number of quality
      decision criteria adhered to, the fewer the risk behaviors exhibited by cancer
      surviving adolescents. Findings indicated that the majority of teen survivors
      reported practicing poor-quality decision making for five of the seven criteria
      (peers, four of seven). There were no significant differences in decision making
      between teen survivors and their peers nor between survivors with cognitive
      threat and those without. Peers were significantly more likely to engage in one
      or more risk behaviors than teen survivors, but comparisons with two normative
      samples (state and national) revealed that cigarette smoking and alcohol use of
      the teen survivors were comparable with the general population. There was no
      significant difference in risk behaviors between survivors with a history of
      therapy with cognitive threat and those without. Survivors who reported higher
      adherence to quality decision criteria were less likely to report exhibiting risk
      behaviors than those with poorer decision making. Using the context of late
      effects due to cancer treatment, oncology nurses need to provide guidance in
      quality decision making as well as in risk behavior education.

PMID- 8755442
TI  - A pilot study to evaluate in-hospital care by mothers.
AB  - Believing that family-centered care is beneficial to children with cancer, the
      staff at Southampton General Hospital in the United Kingdom decided to consider
      instituting care by parents. Before full implementation of care by parents, a
      pilot study involving teaching five mothers of pediatric oncology patients how to
      administer intravenous (i.v.) antibiotics to their child was performed. The basis
      for selecting antibiotic administration was that if the mothers were capable of
      performing such a complex task, they would likely be able to be involved in the
      total care of their child. Mothers' views on the teaching program were sought
      using taped interviews, and the data were analyzed using a line-by-line constant
      comparison analysis. All mothers in the study were capable of performing the
      procedure and all were willing to do so. Mothers emphasized the fact that they
      often feel stressed and out of control because of the impact of disease and
      treatment, and many important issues were raised in relation to this. Nurses'
      attitudes towards care by parents requires clarifying and changes need to take
      place if this concept is to progress. Negotiation to allow mutual understanding
      between parents and nurses is essential to the successful implementation of such
      a care approach.

PMID- 8755443
TI  - Developing education materials for families.

PMID- 8755444
TI  - Busulfan.

PMID- 8755445
TI  - When cancer strikes home.

PMID- 8755446
TI  - [Gas exchange and hemodynamic effects of nitric oxide inhalation in patients with
      acute respiratory distress syndrome].
AB  - BACKGROUND: To analyze the effects on gas exchange and hemodynamics of nitric
      oxide inhalation in patients with acute respiratory distress syndrome. PATIENTS
      AND METHODS: Prospective study including 16 acute respiratory distress syndrome
      patients. We analyzed the acute and short-term (5 days) effects of inhaling 5
      parts per million (ppm) nitric oxide on gas exchange and hemodynamics. RESULTS:
      After nitric oxide inhalation, PaO2/FiO2 ratio changed from 81 +/- 25 to 126 +/-
      57 mmHg (p = 0.0001), mean pulmonary artery pressure decreased from 30.1 +/- 8.2
      to 27.3 +/- 6.6 mmHg (p = 0.002), intrapulmonary shunt decreased from 44.6 +/-
      11% to 34.1 +/- 7.9% (p = 0.002) and cardiac index did not change. Thirteen out
      of 16 patients (81.2%) presented at least a 20% improvement in PaO2/FiO2 ratio.
      In the 10 patients treated over 5 consecutive days, we observed that those who
      improved (increase in PaO2/FiO2 ratio higher than 20% after inhaling 5 ppm nitric
      oxide) showed a lower cardiac index, a higher mean pulmonary artery pressure and
      a higher pulmonary vascular resistance index than those who did not: Cl 3.9 +/-
      0.81 vs 4.9 +/- 0.81 l/min/m2 (p < 0.001), mean pulmonary artery pressure 32.4 +/
      7 vs 25.3 +/- 4.2 mmHg (p = 0.001), and pulmonary vascular resistance index 421
      +/- 199 vs 241 +/- 106 dyn.s.cm5/m2 (p = 0.003). Mean levels of methemoglobin
      were 1.1 +/- 0.24% (range: 0.4-1.6%), and NO2 concentration was always lower than
      100 parts per billion. CONCLUSIONS: Low doses of inhaled nitric oxide induce a
      selective pulmonary vasodilatation and significant improvement of oxygenation in
      the majority of acute respiratory distress syndrome patients, although those with
      a hyperkinetic hemodynamic status are less likely to improve the oxygenation.
      These effects are maintained for at least 5 days. We did not observe rebound
      effects.

PMID- 8755447
TI  - [Impact of diabetes mellitus on hospitalization costs].
AB  - BACKGROUND: To evaluate the impact of diabetes mellitus in hospitals costs.
      PATIENTS AND METHODS: In a general hospital that covers a sanitary area of
      120,873 inhabitants all the hospitalizations of the year 1993 have been analyzed.
      The patients have been classified according to the Patient Management Categories
      version 5.0 system that allows the evaluation of the presence of diabetic
      comorbidity. The direct cost of the stay was calculated by the days of
      hospitalization and consumption of complementary diagnosis tests according to the
      Relative Score of the Patient Management Categories. RESULTS: 5% of the
      hospitalized patients were diabetics. They caused 6% of hospitalizations and
      accounted for 8% of the total expense of hospitalization. The diabetic patients
      had a rate of hospital admission superior to non diabetic (1.4 vs. 1.1; p <
      0.05). The presence of comorbidity was associated to an increase of the risk of
      dying in the inpatient period (odds ratio = 3.4; p < 0.01), to an increase of the
      hospitalization in 3.1 days (p < 0.0001) and to an increment of the cost of 31%
      (p < 0.0001). In the sanitary area the patients with diabetes mellitus caused a
      hospital expense of 193 millions of pesetas/100,000 inhabitants and year.
      CONCLUSIONS: Diabetes mellitus is a very important cause of comorbidity that
      provokes a notable increment of the hospital expenses. The economical impact of
      diabetes mellitus in the costs of hospitalization is so important that the cost
      of the preventive measures for their control would only be a small part of the
      hospital expenses that it generates.

PMID- 8755448
TI  - [Study of the frequency of different phenotypes of alpha-1-antitrypsin in a
      population of Barcelona].
AB  - BACKGROUND: Severe alpha-1-antitrypsin (AAT) deficiency is caused by homozygous
      inheritance of gene Z, and is associated with a high risk of developing pulmonary
      emphysema. Determination of frequencies of different genes associated with the
      deficiency (especially S and Z) gives a clue to estimate the number of
      individuals homozygous PiZZ, carrying a high risk for pulmonary disease, in any
      given population. PATIENTS AND METHODS: Pi phenotypes of 440 healthy individuals
      were determined by means of isoelectrofocusing in polyacrylamide gel. Seric
      values of AAT were determined by immunonephelometry. Mean age of participants was
      30 years (range 18-49 yrs.). Results are compared with other published series.
      RESULTS: Distribution of phenotypes was: PiMM 333 individuals (75%), PiMS 84
      (19%), PiMZ 14 (3%), PiSS 4 (0.9%), PiM 3 (0.6%), PiMF 1 (0.2%), PiMP 1 (0.2%).
      The corresponding gene frequencies were Pi*M 87%, Pi*S 10.4%, and Pi*Z 1.5%.
      Normal values of AAT (phenotype PiMM) established in our laboratory were 116-232
      mg/dl (21-41 micromol/I) (mean +/- 2 SD). According to Hardy-Weinberger equation,
      expected frequency of PiZZ individuals in our area would be 225 per million.
      CONCLUSIONS: The frequency of Z gen individuals observed in our study is one of
      the highest in the Iberian Peninsula, but lower than the frequency in northern
      Europe. According to these results, AAT deficiency (PiZZ) is not a rare condition
      in contrast with the small number of patients diagnosed. The gen frequency of the
      S variant is higher than that of the rest of Europe, and similar to others found
      in some Spanish populations.

PMID- 8755449
TI  - [Retrovirus and human diseases: etiologic agents as therapeutic instruments].

PMID- 8755450
TI  - [Towards a concept of growth hormone deficiency syndrome in adults].

PMID- 8755451
TI  - [Evidence and controversies concerning the association between diet and cancer.
      EPIC (European Prospective Investigation into Cancer) Group in Spain].

PMID- 8755452
TI  - [Diarrhea lasting 8 weeks in a 48-year-old woman].

PMID- 8755453
TI  - [Granulocyte colony-stimulating factor in the treatment of neutropenia associated
      with HIV infection].

PMID- 8755454
TI  - [Measuring the effectiveness of hepatitis B vaccination].

PMID- 8755455
TI  - [Current situation of tuberculosis in Spain. A precarious health care perspective
      with regard to developed countries].

PMID- 8755456
TI  - What is critical is not always intellectually fascinating.

PMID- 8755457
TI  - Familial breast cancer risk assessment.
AB  - A family, with a strong history of dominant breast and ovarian cancer, is
      described. Using highly polymorphic microsatellite markers within the BRCA1
      breast cancer gene on chromosome 17q21; three affected sisters, their father and
      a paternal second cousin once removed, are shown to share the same "abnormal"
      haplotype. Because of this informative linkage, the carrier status of the
      unaffected siblings can be established by determining whether they inherited
      their father's "normal" or "abnormal" haplotype. Presymptomatic diagnosis is
      important in decisions regarding prophylactic surgery or follow-up care. However,
      the widespread general population presymptomatic DNA testing of breast cancer is
      currently not recommended because of inherent problems in the sensitivity and
      specificity of DNA testing.

PMID- 8755458
TI  - America's other drug problem: nonadherence.

PMID- 8755459
TI  - Clonidine: a practical guide for usage in children.
AB  - Clonidine, oral and patch, has been used in adults for the treatment of
      hypertension and Tourette's Syndrome. Recently clinicians have begun to employ it
      in several oft label usages in children, especially behavioral syndromes. This
      article is a guide to its usage in children and includes discussion of its
      indications, contraindications, pre-treatment laboratory studies, dosing and drug
      interactions.

PMID- 8755460
TI  - Surface EMG measurements at the throat during dry and wet swallowing.
AB  - Within the sphere of dysphagia management, there is a growing need for the
      development of noninvasive methods of quantification of swallowing disorders. The
      purpose of the present investigation was to determine if surface electromyogram
      (EMG) at the throat could be measured during swallowing. Surface EMG was measured
      from 35 normal human subjects during dry and wet swallowing. The EMG signals
      recorded were highpass filtered using digital fourth order highpass Butterworth
      filter to eliminate baseline variations. Spectral analysis was performed on the
      filtered signals. The mean power values of the surface EMG signals were then
      calculated. Paired t-test between the mean power values of surface EMG during dry
      and wet swallowing showed a statistically significant difference (p < 0.005). The
      results of the study confirmed the hypothesis that surface EMG at the throat
      during swallowing could be measured. Mean power of surface EMG measurement
      provides a reliable noninvasive measure of swallowing.

PMID- 8755461
TI  - Quantitative aspects of swallowing in an elderly nondysphagic population.
AB  - The prevalence of swallowing impairment increases with age and is a major health
      care problem in the elderly. It has been assumed that age-related changes in
      nerves and muscles hamper muscle strength and coordination of swallowing.
      However, it is unclear what impairment is related to primary aging and what is
      the consequence of diseases prevalent in the elderly (secondary aging). In order
      to quantify swallowing in nondysphagic elderly we used the noninvasive ROSS
      (Repetitive Oral Suction Swallow) test. A total of 53 individuals aged 76 +/- 5
      years (mean +/- SD) were examined. We found that the nondysphagic elderly
      demonstrated significant differences compared with young individuals in 10 of 17
      measured variables, i.e., decreased peak suction pressure, increased frequency of
      multiple swallows after one ingestion, increased frequency of polyphasic
      laryngeal movements, increased frequency of inspiration after swallowing, and
      increased frequency of coughing during or after swallowing. Therefore, primary
      aging mainly seems to influence coordination of swallowing, but oral and
      pharyngeal swallow per se seem to be unaffected.

PMID- 8755462
TI  - A perspective on age-related changes of the swallowing mechanism and their
      clinical significance.

PMID- 8755463
TI  - Modified barium swallow: clinical and radiographic correlation and relation to
      feeding recommendations.
AB  - Clinical and videofluoroscopic evaluation of swallowing were correlated to
      determine their agreement and relationship to feeding recommendations. We
      reviewed a total of 148 patients with swallowing difficulties, of which 93 (45
      women, 48 men; mean age 62 years) were evaluated by both clinical and
      radiographic examinations. A variety of materials were used for clinical bedside
      evaluation of oral and pharyngeal function. Radiographic examination was done
      with variable viscosity materials and videotape recording of the oral cavity and
      pharynx. The severity of oral and pharyngeal abnormalities was graded and
      findings of the examinations were compared. The combined results of both
      evaluations generated an index of swallowing difficulty which was correlated to
      the type of diet used if oral feeding was recommended or to a nonoral route of
      nutrition. In the assessment of oral and pharyngeal dysfunction, clinical
      evaluation and radiographic examination correlated closely in 94% of patients;
      however, the status of pharyngeal function was not determined in 61 (66%) of the
      93 patients by clinical examination alone. The combined swallowing index was
      calculated in 89 patients and its severity correlated significantly with the type
      of feeding recommended; 64 patients were placed on one of three types of diets
      and 25 had enteral feedings. In conclusion, combined clinical and radiographic
      examinations correlated well, but clinical evaluation alone was limited by
      failure to evaluate the pharynx in many patients. The swallowing severity
      correlated well with final feeding recommendations.

PMID- 8755464
TI  - The radiological features of primary small-cell carcinoma of the esophagus.
AB  - Primary small cell carcinoma of the esophagus is a rare neoplasm. The incidence
      was 2% in our series. A primary lung tumor must be excluded before the diagnosis
      can be made. Two cases of primary small-cell carcinoma of the esophagus are
      presented. The radiological features of this tumor are nonspecific. Its unusual
      histological appearance is described. One patients had received radiotherapy for
      breast carcinoma 21 years earlier and the possible relationship of this type of
      cancer to radiotherapy has not been previously described in the literature. Each
      patient had a short-term response to therapy.

PMID- 8755465
TI  - Covert dysphagia in the mentally handicapped: two case reports and a review of
      published literature.
AB  - Mentally handicapped patients with esophageal pathology may present a diagnostic
      challenge, as they may not complain of any specific symptoms or be able to give a
      clear history of either dysphagia or odynophagia. This paper reports 2 such
      patients who recently presented to the Royal Wolverhampton Hospitals. In the
      first case, upper gastrointestinal endoscopy under general anesthesia enabled
      both the identification and removal of a large esophageal foreign body. In the
      second case, repeated upper gastrointestinal endoscopy facilitated both the
      identification and nonsurgical management of a paraesophageal abscess.

PMID- 8755467
TI  - Comments on the effects of cold, touch, and chemical stimulation of the anterior
      faucial pillar on human swallowing.

PMID- 8755466
TI  - The effects of cold, touch, and chemical stimulation of the anterior faucial
      pillar on human swallowing.
AB  - Cold stimulation of the oropharyngeal mucosa, including the faucial pillar
      region, is used a specific technique for the treatment of swallowing disorders.
      The physiological mechanisms underpinning this clinical technique are unclear.
      Thermal (cold), chemical (saline, glucose and water), mechanical (light touch)
      and feigned stimulation of the faucial pillar were assessed for their effects on
      the latency to swallow and the repetitive frequency of swallowing. There was no
      significant difference between these variables following light stimulation of the
      faucial pillar with a metal probe warmed to body temperature compared with
      feigned stimulation. However, cold touch stimulation evoked a significant
      increase in swallowing latency and repetitive frequency compared to feigned
      stimulation. The results suggest the existence of thermo-sensitive receptors in
      the faucial pillars that evoke swallowing when stimulated by cold touch. The
      clinical and physiological importance of these findings are discussed.

PMID- 8755468
TI  - GABA receptor-mediated inhibition of reflex deglutition in the cat.
AB  - In anesthetized cats, swallowing elicited by electrical stimulation of the
      superior laryngeal nerves (SLNs) was inhibited by the GABA-mimetic muscimol and
      by diazepam, an action that was reversed by picrotoxin and bicuculline. This
      inhibition supports the involvement of GABA receptors, specifically those of the
      GABAA subtype which both antagonists have been shown to block in various areas of
      the central nervous system. The inhibition of reflex swallowing and its reversal
      were unaltered by a transection of the brainstem at a midcollicular level.
      Stimulation of the SLNs also caused a bradycardia that was inhibited by both
      muscimol and diazepam and was restored by both GABA antagonists. Data from these
      experiments provide suggestive evidence for a role of GABA-ergic transmission in
      the central control of the deglutitory reflex.

PMID- 8755469
TI  - The Burke Dysphagia Screening Test: validation of its use in patients with
      stroke.

PMID- 8755470
TI  - Solid-state computerized manometry improves diagnostic yield in pharyngeal
      dysphagia: simultaneous videoradiography and manometry in dysphagia patients with
      normal barium swallows.

PMID- 8755471
TI  - Response to Kim et al.: a prospective psychological evaluation of patients with
      dysphagia of various etiologies.

PMID- 8755472
TI  - Numb diverts notch pathway off the tramtrack.

PMID- 8755473
TI  - Transcriptional regulation of axon pathfinding.

PMID- 8755474
TI  - Eph receptors and ligands comprise two major specificity subclasses and are
      reciprocally compartmentalized during embryogenesis.
AB  - We report that the many Eph-related receptor tyrosine kinases, and their numerous
      membrane-bound ligands, can each be grouped into only two major specificity
      subclasses. Receptors in a given subclass bind most members of a corresponding
      ligand subclass. The physiological relevance of these groupings is suggested by
      viewing the collective distributions of all members of a subclass. These
      composite distributions, in contrast with less informative patterns seen with
      individual members of the family, reveal that the developing embryo is subdivided
      into domains defined by reciprocal and apparently mutually exclusive expression
      of a receptor subclass and its corresponding ligands. Receptors seem to encounter
      their ligands only at the interface between these domains. This reciprocal
      compartmentalization implicates the Eph family in the formation of spatial
      boundaries that may help to organize the developing body plan.

PMID- 8755475
TI  - Numb antagonizes Notch signaling to specify sibling neuron cell fates.
AB  - Asymmetric cell divisions play a key role in establishing neuronal diversity in
      the mammalian and Drosophila CNS, but the mechanisms involved are mostly unknown.
      The Drosophila MP2 precursor divides asymmetrically to generate the dMP2/vMP2
      interneurons. Delta-Notch signaling is required to specify vMP2 fate, whereas the
      localized determinant Numb is segregated into dMP2 and is required to specify
      dMP2 fate. Notch; numb double mutants have two dMP2 neurons; hence, Numb is not
      required for dMP2 fate, but antagonizes the Delta-Notch "vMP2" signal. In vivo
      Delta expression and in vitro culture experiments show that vMP2 fate is
      specified by an "inductive" signal from outside the MP2 lineage. Thus, intrinsic
      and extrinsic cues converge to specify binary cell fates in the MP2 cell lineage.

PMID- 8755476
TI  - Control of daughter cell fates during asymmetric division: interaction of Numb
      and Notch.
AB  - During development of the Drosophila peripheral nervous system, a sensory organ
      precursor (SOP) cell undergoes rounds of asymmetric divisions to generate four
      distinct cells of a sensory organ. Numb, a membrane-associated protein, is
      asymmetrically segregated into one daughter cell during SOP division and acts as
      an inherited determinant of cell fate. Here, we show that Notch, a transmembrane
      receptor mediated cell-cell communication, functions as a binary switch in cell
      fate specification during asymmetric divisions of the SOP and its daughter cells
      in embryogenesis. Moreover, numb negatively regulates Notch, probably through
      direct protein-protein interaction that requires the phosphotyrosine-binding
      (PTB) domain of Numb and either the RAM23 region or the very C-terminal end of
      Notch. Notch then positively regulates a transcription factor encoded by
      tramtrack (ttk). This leads to Ttk expression in the daughter cell that does not
      inherit Numb. Thus, the inherited determinant Numb bestows a bias in the
      machinery for cell-cell communication to allow the specification of distinct
      daughter cell fates.

PMID- 8755477
TI  - Asymmetric localization of a mammalian numb homolog during mouse cortical
      neurogenesis.
AB  - During Drosophila neurogenesis, differential segregation of Numb is necessary for
      daughter cells of asymmetric divisions to adopt distinct fates, at least partly
      by biasing the Notch-mediated cell-cell interaction. We have isolated a highly
      conserved mammalian homolog of Drosophila numb, m-numb. During mouse cortical
      neurogenesis, m-Numb is asymmetrically localized to the apical membrane of
      dividing ventricular neural progenitors. Depending upon the orientation of the
      cleavage plane, m-Numb may be distributed into one or both of the daughter cells.
      When expressed in Drosophila embryos, m-Numb is localized asymmetrically in
      dividing neural precursors and rescues the numb mutant phenotype. Furthermore, m
      Numb can physically interact with mouse Notch1. We propose that some shared
      molecular mechanisms, both cell-intrinsic and cell-extrinsic, generate asymmetric
      cell divisions during neurogenesis of vertebrates and invertebrates.

PMID- 8755478
TI  - Restriction of late cerebral cortical progenitors to an upper-layer fate.
AB  - Early in development, neural progenitors in cerebral cortex normally produce
      neurons of several layers during successive cell divisions. The laminar fate of
      their daughters depends on environmental cues encountered just before mitosis. At
      the close of neurogenesis, however, cortical progenitors normally produce neurons
      destined only for the upper layers. To assess the developmental potential of
      these cells, upper-layer progenitors were transplanted into the cerebral cortex
      of younger hosts, in which deep-layer neurons were being generated. These studies
      reveal that late cortical progenitors are not competent to generate deep-layer
      neurons and are instead restricted to producing the upper layers.

PMID- 8755479
TI  - Cardiotrophin-1, a cytokine present in embryonic muscle, supports long-term
      survival of spinal motoneurons.
AB  - The muscle-derived factors required for survival of embryonic motoneurons are not
      clearly identified. Cardiotrophin-1 (CT-1), a cytokine related to ciliary
      neurotrophic factor (CNTF), is expressed at high levels in embryonic limb bud and
      is secreted by differentiated myotubes. In vitro, CT-1 kept 43% of purified E14
      rat motoneurons alive for 2 weeks (EC50 = 20 pM). In vivo, CT-1 protected
      neonatal sciatic motoneurons against the effects of axotomy. CT-1 action on
      motoneurons was inhibited by phosphatidylinositol-specific phospholipase C
      (PIPLC), suggesting that CT-1 may act through a GPI-linked component. Since no
      binding of CT-1 to CNTFR alpha was detected, CT-1 may use a novel cytokine
      receptor alpha subunit. CT-1 may be important in normal motoneuron development
      and as a potential tool for slowing motoneuron degeneration in human diseases.

PMID- 8755481
TI  - Evidence for a role of dendritic filopodia in synaptogenesis and spine formation.
AB  - Axo-dendritic synaptogenesis was examined in live hippocampal cell cultures using
      the fluorescent dyes DiO to label dendrites and FM 4-64 to label functional
      presynaptic boutons. As the first functional synaptic boutons appeared in these
      cultures, numerous filopodia (up to 10 micron long) were observed to extend
      transiently (mean lifetime 9.5 min) from dendritic shafts. With progressively
      increasing numbers of boutons, there were coincident decreases in numbers of
      transient filopodia and increases in numbers of stable dendritic spines.
      Dendritic filopodia were observed to initiate physical contacts with nearby
      axons. This sometimes resulted in filopodial stabilization and formation of
      functional presynaptic boutons. These findings suggest that dendritic filopodia
      may actively initiate synaptogenic contacts with nearby (5-10 micron) axons and
      thereafter evolve into dendritic spines.

PMID- 8755480
TI  - Inactivation of bcl-2 results in progressive degeneration of motoneurons,
      sympathetic and sensory neurons during early postnatal development.
AB  - Bcl-2 is a major regulator of programmed cell death, a critical process in
      shaping the developing nervous system. To assess whether Bcl-2 is involved in
      regulating neuronal survival and in mediating the neuroprotective action of
      neurotrophic factors, we generated Bcl-2-deficient mice. At birth, the number of
      facial motoneurons, sensory, and sympathetic neurons was not significantly
      changed, and axotomy-induced degeneration of facial motoneurons could still be
      prevented by brain-derived neurotrophic factor (BDNF) or ciliary neurotrophic
      factor (CNTF). Interestingly, substantial degeneration of motoneurons, sensory,
      and sympathetic neurons occurred after the physiological cell death period.
      Accordingly, Bcl-2 is not a permissive factor for the action of neurotrophic
      factors, and although it does not influence prenatal neuronal survival, it is
      crucial for the maintenance of specific populations of neurons during the early
      postnatal period.

PMID- 8755482
TI  - Heteromultimerization and NMDA receptor-clustering activity of Chapsyn-110, a
      member of the PSD-95 family of proteins.
AB  - Chapsyn-110, a novel membrane-associated putative guanylate kinase (MAGUK) that
      binds directly to N-methyl-D-aspartate (NMDA) receptor and Shaker K+ channel
      subunits, is 70%-80% identical to, and shares an identical domain organization
      with, PSD-95/SAP90 and SAP97. In rat brain, chapsyn-110 protein shows a
      somatodendritic expression pattern that overlaps partly with PSD-95 but that
      contrasts with the axonal distribution of SAP97. Chapsyn-110 associates tightly
      with the postsynaptic density in brain, and mediates the clustering of both NMDA
      receptors and K+ channels in heterologous cells. Indeed, chapsyn-110 and PSD-95
      can heteromultimerize with each other and are recruited into the same NMDA
      receptor and K+ channel clusters. Thus, chapsyn-110 and PSD-95 may interact at
      postsynaptic sites to form a multimeric scaffold for the clustering of receptors,
      ion channels, and associated signalling proteins.

PMID- 8755483
TI  - Posttranslational regulation of Ca(2+)-activated K+ currents by a target-derived
      factor in developing parasympathetic neurons.
AB  - Macroscopic IK[Ca is not expressed in normal levels in chick ciliary ganglion
      (CG) neurons prior to synapse formation with target tissues, or in neurons
      developing in vitro or in situ in the absence of target tissues. Here, two chick
      CG slo partial cDNAs encoding IK[Ca channels were isolated, cloned, and
      sequenced. Both slo transcripts were readily detected in developing CG neurons
      prior to or in the absence of target tissue interactions. When CG neurons
      developed in vitro in the presence of target tissue (iris) extracts, a normal
      whole-cell IK[Ca was expressed. These effects did not require protein synthesis,
      and the activity was detectable throughout the stages of synapse formation in the
      iris. The active component has an apparent molecular weight of 40-60 kDa.

PMID- 8755484
TI  - Potentiation of evoked vesicle turnover at individually resolved synaptic
      boutons.
AB  - We have studied synaptic plasticity in hippocampal cell cultures using a new
      imaging approach that allows unambiguous discrimination of presynaptic function
      at the level of single synaptic boutons. Employing a protocol designed to test
      for use-dependent plasticity resembling N-methyl-D-aspartate receptor-dependent
      long-term potentiation (NMDA-type LTP), we find that brief tetanic stimuli induce
      a potentiation of evoked synaptic vesicle turnover that lasts for at least 1 hr.
      Induction of this clearly presynaptic potentiation is blocked by putative
      postsynaptic glutamate receptor antagonists, suggesting that a retrograde
      induction signal might be involved. Potentiation appears to occur approximately
      equally at boutons of low and high initial release probabilities, and evidently
      does not involve an increase in the size of the total recycling synaptic vesicle
      pool.

PMID- 8755485
TI  - Ca(2+)-dependent exocytosis in the somata of dorsal root ganglion neurons.
AB  - Using capacitance measurements and the single-cell immunoblot assay to study
      secretion in dorsal root ganglion neurons, we found that the somata underwent
      robust exocytosis upon depolarization and released substance P, in response to
      KCl stimulation. The parallel changes between capacitance responses and
      intracellular Ca2+ concentration ([Ca2+]i) at different membrane potentials and
      the inhibition of exocytosis by Ca2+ chelators suggest that soma release is
      Ca(2+)-dependent. We also assessed the level of Ca2+ required for exocytosis by
      raising the average [Ca2+]i with the Ca2+ ionophore, ionomycin. Capacitance
      changes were triggered by cytosolic Ca2+ > 0.6 microM; the [Ca2+]i at the release
      sites during depolarizations was estimated to be 3-10 microM. These Ca2+ levels
      are similar to those obtained from neuroendocrine cells, but are at least 10
      times lower than those required for transmitter release from nerve terminals.

PMID- 8755486
TI  - Network-level changes in expression of inducible Fos-Jun proteins in the striatum
      during chronic cocaine treatment and withdrawal.
AB  - Repeated exposure to psychomotor stimulants produce long-term changes in behavior
      ranging from addiction to behavioral sensitization. Many of these behaviors
      depend on the nigrostriatal system of the basal ganglia. We show here that
      chronic cocaine exposure not only leads to time-varying alterations in the
      inducibility of bZIP transcription factors in individual striatal neurons, but
      also to long-lasting network changes in which ensembles of striatal neurons
      express these proteins. These network-level adaptations suggest that the
      behavioral sensitization induced by repeated psychomotor stimulant exposure may
      reflect an enduring functional reorganization of basal ganglia circuits.

PMID- 8755487
TI  - Congenital myasthenic syndrome caused by decreased agonist binding affinity due
      to a mutation in the acetylcholine receptor epsilon subunit.
AB  - We describe the genetic and kinetic defects for a low-affinity fast channel
      disease of the acetylcholine receptor (AChR) that causes a myasthenic syndrome.
      In two unrelated patients with very small miniature end plate (EP) potentials,
      but with normal EP AChR density and normal EP ultrastructure, patch-clamp studies
      demonstrated infrequent AChR channel events, diminished channel reopenings during
      ACh occupancy, and resistance to desensitization by ACh. Each patient had two
      heteroallelic AChR epsilon subunit gene mutations: a common epsilon P121L
      mutation, a signal peptide mutation (epsilon G-8R) (patient 1), and a
      glycosylation consensus site mutation (epsilon S143L) (patient 2). AChR
      expression in HEK fibroblasts was normal with epsilon P121L but was markedly
      reduced with the other mutations. Therefore, epsilon P121L defines the clinical
      phenotype. Studies of the engineered epsilon P121L AChR revealed a markedly
      decreased rate of channel opening, little change in affinity of the resting state
      for ACh, but reduced affinity of the open channel and desensitized states.

PMID- 8755488
TI  - Inhibition of amyloid beta-protein production in neural cells by the serine
      protease inhibitor AEBSF.
AB  - Cerebral deposition of amyloid beta protein (A beta) is an early and critical
      feature of Alzheimer's disease. A beta production requires the proteolytic
      release of A beta from the beta-amyloid precursor protein (beta APP). Thus,
      inhibition of A beta release is a prime therapeutic goal. Here, we show that the
      broad spectrum, irreversible serine protease inhibitor, AEBSF, inhibits the
      constitutive production of A beta in five different human cell lines, both neural
      and nonneural. AEBSF also stabilizes full-length beta APP and enhances alpha
      secretion, as shown by an increase in the proteolytic derivative, alpha-APPS.
      Further, we demonstrate that the inhibitory effect of AEBSF is specific for A
      beta proteins starting at Aspartate 1, suggesting that AEBSF directly inhibits
      beta-secretase, the Methionine-Aspartate (Met-Asp)-cleaving enzyme. These results
      indicate that specific inhibition of this A beta-generating protease is possible
      in living human neural cells and provide information about the characteristics of
      this as yet unidentified enzyme.

PMID- 8755489
TI  - Endoproteolysis of presenilin 1 and accumulation of processed derivatives in
      vivo.
AB  - The majority of early-onset cases of familial Alzheimer's disease (FAD) are
      linked to mutations in two related genes, PS1 and PS2, located on chromosome 14
      and 1, respectively. Using two highly specific antibodies against nonoverlapping
      epitopes of the PS1-encoded polypeptide, termed presenilin 1 (PS1), we document
      that the preponderant PS1-related species that accumulate in cultured mammalian
      cells, and in the brains of rodents, primates, and humans are approximately 27-28
      kDa N-terminal and approximately 16-17 kDa C-terminal derivatives. Notably, a FAD
      linked PS1 variant that lacks exon 9 is not subject to endoproteolytic cleavage.
      In brains of transgenic mice expressing human PS1, approximately 17 kDa and
      approximately 27 kDa PS1 derivatives accumulate to saturable levels, and at
      approximately 1:1 stoichiometry, independent of transgene-derived mRNA. We
      conclude that PS1 is subject to endoproteolytic processing in vivo.

PMID- 8755490
TI  - Error-prone retrotransposition: rime of the ancient mutators.

PMID- 8755491
TI  - Second-hand chloroplasts and the case of the disappearing nucleus.

PMID- 8755492
TI  - Photo-induced inactivation of viruses: adsorption of methylene blue, thionine,
      and thiopyronine on Qbeta bacteriophage.
AB  - The adsorption of cationic organic dyes (methylene blue, thionine, and
      thiopyronine) on Qbeta bacteriophage was studied by UV-visible and fluorescence
      spectroscopy. The dyes have shown a strong affinity to the virus and some have
      been used as sensitizers for photo-induced inactivation of virus. In the
      methylene blue concentration range of 0.1-5 microM and at high ratios of dye to
      virus (greater than 1000 dye molecules per virion), the dyes bind as aggregates
      on the virus. Aggregation lowers the efficiency of photoinactivation because of
      self-quenching of the dye. At lower ratios of dye to virus (lower than 500 dye
      molecules per virion), the dye binds to the virus as a monomer. Fluorescence
      polarization and time-resolved studies of the fluorescence support the
      conclusions based on fluorescence quenching. Increasing the ionic strength
      (adding NaCl) dissociates bound dye aggregates on the virus and releases
      monomeric dye into the bulk solution.

PMID- 8755493
TI  - Persistent confusion of total entropy and chemical system entropy in chemical
      thermodynamics.
AB  - The change in free energy with temperature at constant pressure of a chemical
      reaction is determined by the sum (dS) of changes in entropy of the system of
      reagents, dS(i), and the additional entropy change of the surroundings, dS(H),
      that results from the enthalpy change, W. A faulty identification of the total
      entropy change on reaction with dS(i) has been responsible for the attribution of
      general validity to the expressions (d deltaG/dT)p = -deltaS(i) and
      d(deltaG/T)/d(1/T)= deltaH, which are found in most textbooks and in innumerable
      papers.

PMID- 8755494
TI  - Magnetic resonance microscopy and spectroscopy reveal kinetics of cryoprotectant
      permeation in a multicompartmental biological system.
AB  - Successful cryopreservation of most multicompartmental biological systems has not
      been achieved. One prerequisite for success is quantitative information on
      cryoprotectant permeation into and amongst the compartments. This report
      describes direct measurements of cryoprotectant permeation into a
      multicompartmental system using chemical shift selective magnetic resonance (MR)
      microscopy and MR spectroscopy. We used the developing zebrafish embryo as a
      model for studying these complex systems because these embryos are composed of
      two membrane-limited compartments: (i) a large yolk (surrounded by the yolk
      syncytial layer) and (ii) differentiating blastoderm cells (each surrounded by a
      plasma membrane). MR images of the spatial distribution of three cryoprotectants
      (dimethyl sulfoxide, propylene glycol, and methanol) demonstrated that methanol
      permeated the entire embryo within 15 min. In contrast, the other cryoprotectants
      exhibited little or no permeation over 2.5 h. MR spectroscopy and microinjections
      of cryoprotectants into the yolk inferred that the yolk syncytial layer plays a
      critical role in limiting the permeation of some cryoprotectants throughout the
      embryo. This study demonstrates the power of MR technology combined with
      micromanipulation for elucidating key physiological factors in cryobiology.

PMID- 8755495
TI  - In vivo tissue distribution of CD4 lymphocytes in mice determined by
      radioimmunoscintigraphy with an 111In-labeled anti-CD4 monoclonal antibody.
AB  - The tissue distribution of CD4 lymphocytes in normal C57/BL mice and CD4 knockout
      mice was determined by biodistribution measurements and gamma camera imaging with
      an 111In-labeled rat IgG2b monoclonal antibody directed against the murine CD-4
      antigen. In normal mice high concentrations of antibody accumulated in the spleen
      and lymph nodes. At 45 hr after injection, the concentration of radiolabel in the
      spleen and lymph nodes of normal mice were 10- to 20-fold greater than in the
      corresponding tissue of the CD4 knockout mice and nonlymphoid tissues of both
      types of mice. At 24 and 45 hr, gamma camera images showed high concentrations of
      radiolabeled antibody in lymph node and spleen of normal but not knockout mice.
      These results indicate that radioimmunoscintigraphy with 111In-anti-CD4 is an
      excellent method for studying tissue distribution of CD lymphocytes in mice.
      Using an equivalent anti-human CD antibody, this method might be useful for
      studying the pathophysiology of conditions in which these cells play a critical
      role and for monitoring therapies for these disorders.

PMID- 8755496
TI  - In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine
      protease containing two FADD-like domains.
AB  - Emerging evidence suggests that an amplifiable protease cascade consisting of
      multiple aspartate specific cysteine proteases (ASCPs) is responsible for the
      apoptotic changes observed in mammalian cells undergoing programmed cell death.
      Here we describe the cloning of two novel ASCPs from human Jurkat T-lymphocytes.
      Like other ASCPs, the new proteases, named Mch4 and Mch5, are derived from single
      chain proenzymes. However, their putative active sites contain a QACQG
      pentapeptide instead of the QACRG present in ail known ASCPs. Also, their N
      termini contain FADD-like death effector domains, suggesting possible interaction
      with FADD. Expression of Mch4 in Escherichia coli produced an active protease
      that, like other ASCPs, was potently inhibited (Kj = 14 nM) by the tetrapeptide
      aldehyde DEVD-CHO. Interestingly, both Mch4 and the serine protease granzyme B
      cleave recombinant proCPP32 and proMch3 at a conserved IXXD-S sequence to produce
      the large and small subunits of the active proteases. Granzyme B also cleaves
      proMch4 at a homologous IXXD-A processing sequence to produce mature Mch4. These
      observations suggest that CPP32 and Mch3 are targets of mature Mch4 protease in
      apoptotic cells. The presence of the FADD-like domains in Mch4 and Mch5 suggests
      a role for these proteases in the Fas-apoptotic pathway. In addition, these
      proteases could participate in the granzyme B apoptotic pathways.

PMID- 8755497
TI  - An interspecies hybrid RNA virus is significantly more virulent than either
      parental virus.
AB  - Cucumber mosaic cucumovirus (CMV) infects a very wide range of plant species
      (>1000 species). We recently demonstrated that a previously undescribed gene (2b)
      encoded by RNA 2 of the tripartite RNA genome of CMV is required for systemic
      virus spread and disease induction in its hosts. Herein we report that when this
      CMV gene is replaced by its homologue from tomato aspermy cucumovirus (TAV), the
      resultant hybrid virus is significantly more virulent, induces earlier onset of
      systemic symptoms, and accumulates to a higher level in seven host species from
      three families than either of the parents. Our results indicate that CMV and the
      TAV 2b protein interact synergistically despite the fact that no synergism occurs
      in double infections with the two parental viruses. To our knowledge, this is the
      first example of an interspecific hybrid made from plant or animal RNA viruses
      that is more efficient in systemic infection of a number of hosts than the
      naturally occurring parents. As CMV and the hybrid virus accumulated to a similar
      level in the infected tobacco protoplasts, the observed synergistic responses
      most likely resulted from an increased efficacy of the hybrid virus in systemic
      spread in host plants provided by the TAV 2b protein. The relevance of our
      finding to the application of pathogen-derived resistance is discussed.

PMID- 8755498
TI  - Anti-peptide aptamers recognize amino acid sequence and bind a protein epitope.
AB  - In vitro selection of nucleic acid binding species (aptamers) is superficially
      similar to the immune response. Both processes produce biopolymers that can
      recognize targets with high affinity and specificity. While antibodies are known
      to recognize the sequence and conformation of protein surface features
      (epitopes), very little is known about the precise interactions between aptamers
      and their epitopes. Therefore, aptamers that could recognize a particular
      epitope, a peptide fragment of human immunodeficiency virus type I Rev, were
      selected from a random sequence RNA pool. Several of the selected RNAs could bind
      the free peptide more tightly than a natural RNA ligand, the Rev-binding element.
      In accord with the hypothesis that protein and nucleic acid binding cusps are
      functionally similar, interactions between aptamers and the peptide target could
      be disrupted by sequence substitutions. Moreover, the aptamers appeared to be
      able to bind peptides with different solution conformations, implying an induced
      fit mechanism for binding. Just as anti-peptide antibodies can sometimes
      recognize the corresponding epitope when presented in a protein, the anti-peptide
      aptamers were found to specifically bind to Rev.

PMID- 8755499
TI  - Structure of the catalytic fragment of poly(AD-ribose) polymerase from chicken.
AB  - The crystal structures of the catalytic fragment of chicken poly(ADP-ribose)
      polymerase [NAD+ ADP-ribosyltransferase; NAD+:poly(adenosine-diphosphate-D
      ribosyl)-acceptor ADP-D-ribosyltransferase, EC 2.4.2.30] with and without a
      nicotinamide-analogue inhibitor have been elucidated. Because this enzyme is
      involved in the regulation of DNA repair, its inhibitors are of interest for
      cancer therapy. The inhibitor shows the nicotinamide site and also suggests the
      adenosine site. The enzyme is structurally related to bacterial ADP-ribosylating
      toxins but contains an additional alpha-helical domain that is suggested to relay
      the activation signal issued on binding to damaged DNA.

PMID- 8755500
TI  - Use of engineered ribozymes to catalyze chimeric gene assembly.
AB  - We report the use of engineered ribozymes to shuffle exon cassettes in vitro.
      Specifically, we have designed derivatives of a group II intron that insert into
      selected sites in the human tissue plasminogen activator (t-PA) mRNA. The
      insertion reaction links t-PA sequences to the group II intron sequences so that
      trans-splicing reactions catalyzed by the intron can be employed to shuffle the t
      PA sequences. We expect these results to be generalizable, so that similar
      ribozymes can be designed to target any desired 13 nucleotide sequence. In
      principle, the reactions we describe here should be able to link any RNA molecule
      to any other RNA molecule at any selected point.

PMID- 8755501
TI  - Enzymatic phosphorylation of muscle glycogen synthase: a mechanism for
      maintenance of metabolic homeostasis.
AB  - We recently analyzed experimental studies of mammalian muscle glycogen synthesis
      using metabolic control analysis and concluded that glycogen synthase (GSase)
      does not control the glycogenic flux but rather adapts to the flux which is
      controlled bv the activity of the proximal glucose transport and hexokinase
      steps. This model did not provide a role for the well established relationship
      between GSase fractional activity, determined by covalent phosphorylation, and
      the rate of glycogen synthesis. Here we propose that the phosphorylation of
      GSase, which alters the sensitivity to allosteric activation by glucose 6
      phosphate (G6P), is a mechanism for controlling the concentration of G6P instead
      of controlling the flux. When the muscle cell is exposed to conditions which
      favor glycogen synthesis such as high plasma insulin and glucose concentrations
      the fractional activity of GSase is increased in coordination with increases in
      the activity of glucose transport and hexokinase. This increase in GSase
      fractional activity helps to maintain G6P homeostasis by reducing the G6P
      concentration required to activate GSase allosterically to match the flux
      determined by the proximal reactions. This role for covalent phosphorylation also
      provides a novel solution to the Kacser and Acarenza paradigm which requires
      coordinated activity changes of the enzymes proximal and distal to a shared
      intermediate, to avoid unwanted flux changes.

PMID- 8755502
TI  - Crystal structure of D-amino acid oxidase: a case of active site mirror-image
      convergent evolution with flavocytochrome b2.
AB  - D-amino acid oxidase is the prototype of the FAD-dependent oxidases. It catalyses
      the oxidation of D-amino acids to the corresponding alpha-ketoacids. The reducing
      equivalents are transferred to molecular oxygen with production of hydrogen
      peroxide. We have solved the crystal structure of the complex of D-amino acid
      oxidase with benzoate, a competitive inhibitor of the substrate, by single
      isomorphous replacement and eightfold averaging. Each monomer is formed by two
      domains with an overall topology similar to that of p-hydroxybenzoate
      hydroxylase. The benzoate molecule lays parallel to the flavin ring and is held
      in position by a salt bridge with Arg-283. Analysis of the active site shows that
      no side chains are properly positioned to act as the postulated base required for
      the catalytic carboanion mechanism. On the contrary, the benzoate binding mode
      suggests a direct transfer of the substrate alpha-hydrogen to the flavin during
      the enzyme reductive half-reaction. The active site Of D-amino acid oxidase
      exhibits a striking similarity with that of flavocytochrome b2, a structurally
      unrelated FMN-dependent flavoenzyme. The active site groups (if these two enzymes
      are in fact superimposable once the mirror-image of the flavocytochrome b2 active
      site is generated with respect to the flavin plane. Therefore, the catalytic
      sites of D-amino acid oxidase and flavocytochrome b2 appear to have converged to
      a highly similar but enantiomeric architecture in order to catalvze similar
      reactions (oxidation of alpha-amino acids or alpha-hydroxy acids), although with
      opposite stereochemistry.

PMID- 8755503
TI  - Cryo-electron microscopy studies of empty capsids of human parvovirus B19
      complexed with its cellular receptor.
AB  - The three-dimensional structures of human parvovirus B19 VP2 capsids, alone and
      complexed with its cellular receptor, globoside, have been determined to 26
      resolution. The B19 capsid structure, reconstructed from cryo-electron
      micrographs of vitrified specimens, has depressions on the icosahedral 2-fold and
      3-fold axes, as well as a canyon-like region around the 5-fold axes. Similar
      results had previously been found in an 8 angstrom resolution map derived from x
      ray diffraction data. Other parvoviral structures have a cylindrical channel
      along the 5-fold icosahedral axes, whereas density covers the 5-fold axes in B19.
      The glycolipid receptor molecules bind into the depressions on the 3-fold axes of
      the B19:globoside complex. A model of the tetrasaccharide component of globoside,
      organized as a trimeric fiber, fits well into the difference density representing
      the globoside receptor. Escape mutations to neutralizing antibodies map onto th
      capsid surface at regions immediately surrounding the globoside attachment sites.
      The proximity of the antigenic epitopes to the receptor site suggests that
      neutralization of virus infectivity is caused by preventing attachment of viruses
      to cells.

PMID- 8755504
TI  - Evolutionarily conserved Galphabetagamma binding surfaces support a model of the
      G protein-receptor complex.
AB  - The pivotal role of G proteins in sensory, hormonal, inflammatory, and
      proliferative responses has provoked intense interest in understanding how they
      interact with their receptors and effectors. Nonetheless, the locations of the
      receptors and effector binding sites remain poorly characterized, although nearly
      complete structures of the alphabetagamma heterotrimeric complex are available.
      Here we apply evolutionary trace (ET) analysis [Lichtarge, O., Bourne, H. R. &
      Cohen, F. E. (1996) J. Mol. Biol. 257, 342-358] to propose plausible locations
      for these sites. On each subunit, ET identifies evolutionarily selected surfaces
      composed of residues that do not vary within functional subgroups and that form
      spatial clusters. Four clusters correctly identify subunit interfaces, and
      additional clusters on Galpha point to likely receptor or effector binding sites.
      Our results implicate the conformationally variable region of Galpha in an
      effector binding role. Furthermore the range of predicted interactions between
      the receptor and Galphabetagamma, is sufficiently limited that we can build a low
      resolution and testable model of the receptor-G protein complex.

PMID- 8755505
TI  - Intermolecular disulfide bonds stabilize VirB7 homodimers and VirB7/VirB9
      heterodimers during biogenesis of the Agrobacterium tumefaciens T-complex
      transport apparatus.
AB  - The Agrobacterium tumefaciens VirB7 lipoprotein contributes to the stabilization
      of VirB proteins during biogenesis of the putative T-complex transport apparatus.
      Here, we report that stabilization of VirB7 itself is correlated with its ability
      to form disulfide cross-linked homodimers via a reactive Cys-24 residue. Three
      types of beta-mercaptoethanol-dissociable complexes were visualized with VirB7
      and/or a VirB7::PhoA41 fusion protein: (i) a 9-kDa complex corresponding in size
      to a VirB7 homodimer, (ii) a 54-kDa complex corresponding in size to a
      VirB7/VirB7::PhoA41 mixed dimer, and (iii) a 102-kDa complex corresponding to a
      VirB7::PhoA41 homodimer. A VirB7C24S mutant protein was immunologically
      undetectable, whereas the corresponding VirB7C24S::PhoA41 derivative accumulated
      to detectable levels but failed to form dissociable homodimers or mixed dimers
      with wild-type VirB7. We further report that VirB7-dependent stabilization of
      VirB9 is correlated with the ability of these two proteins to dimerize via
      formation of a disulfide bridge between reactive Cys-24 and Cys-262 residues,
      respectively. Two types of dissociable complexes were visualized: (i) a 36-kDa
      complex corresponding in size to a VirB7/VirB9 heterodimer and (ii) an 84-kDa
      complex corresponding in size to a VirB7/VirB9::PhoA293 heterodimer. A VirB9C262S
      mutant protein was immunologically undetectable, whereas the corresponding
      VirB9C262S::PhoA293 derivative accumulated to detectable levels but failed to
      form dissociable heterodimers with wild-type VirB7. Taken together, these results
      support a model in which the formation of disulfide cross-linked VirB7 dimers
      represent critical early steps in the biogenesis of the T-complex transport
      apparatus.

PMID- 8755506
TI  - Enhanced phospholipase C-gamma1 activity produced by association of independently
      expressed X and Y domain polypeptides.
AB  - The X and Y domains of phospholipase C (PLC)-gamma1, which are conserved in all
      mammalian phosphoinositide-specific PLC isoforms and are proposed to interact to
      form the catalytic site, have been expressed as individual hexahistidine-tagged
      fusion proteins in the baculovirus system. Following coinfection of insect cells
      with recombinant viruses, association of X and Y polypeptides was demonstrated in
      coprecipitation assays. When enzyme activity was examined, neither domain
      possessed catalytic activity when expressed alone; however, coexpression of the X
      and Y polypeptides produced a functional enzyme. This reconstituted phospholipase
      activity remained completely dependent on the presence of free Ca2+. The specific
      activity of the X:Y complex was significantly greater (20- to 100-fold) than that
      of holoPLC-gamma1 and was only moderately influenced by varying the concentration
      of substrate. The enzyme activities of holoPLC-gamma1 and the X:Y complex
      exhibited distinct pH optima. For holoPLC-gamma1 maximal activity was detected at
      pH 5.0, while activity of the X:Y complex was maximal at pH 7.2.

PMID- 8755507
TI  - Host range restrictions of oncogenes: myc genes transform avian but not mammalian
      cells and mht/raf genes transform mammalian but not avian cells.
AB  - The host range of retroviral oncogenes is naturally limited by the host range of
      the retroviral vector. The question of whether the transforming host range of
      retroviral oncogenes is also restricted by the host species has not been directly
      addressed. Here we have tested in avian and murine host species the transforming
      host range of two retroviral onc genes, myc of avian carcinoma viruses MH2 and
      MC29 and mht/raf of avian carcinoma virus MH2 and murine sarcoma virus MSV 3611.
      Virus vector-mediated host restriction was bypassed by recombining viral
      oncogenes with retroviral vectors that can readily infect the host to be tested.
      It was found that, despite high expression, transforming function of retroviral
      myc genes is restricted to avian cells, and that of retroviral mht/raf genes is
      restricted to murine cells. Since retroviral oncogenes encode the same proteins
      as certain cellular genes, termed protooncogenes, our data must also be relevant
      to the oncogene hypothesis of cancer. According to this hypothesis, cancer is
      caused by mutation of protooncogenes. Because protooncogenes are conserved in
      evolution and are presumed to have conserved functions, the oncogene hypothesis
      assumes no host range restriction of transforming function. For example, mutated
      human proto-myc is postulated to cause Burkitt lymphoma, because avian
      retroviruses with myc genes cause cancer in birds. But there is no evidence that
      known mutated protooncogenes can transform human cells. The findings reported
      here indicate that host range restriction appears to be one of the reasons (in
      addition to insufficient transcriptional activation) why known, mutated
      protooncogenes lack transforming function in human cells.

PMID- 8755508
TI  - COOH-terminal processing of nascent polypeptides by the
      glycosylphosphatidylinositol transamidase in the presence of hydrazine is
      governed by the same parameters as glycosylphosphatidylinositol addition.
AB  - Proteins anchored to the cell membrane via a glycosylphosphatidylinositol (GPI)
      moiety are found in all eukaryotes. After NH2-terminal peptide cleavage of the
      nascent protein by the signal peptidase, a second COOH-terminal signal peptide is
      cleaved with the concomitant addition of the GPI unit. The proposed mechanism of
      the GPI transfer is a transamidation reaction that involves the formation of an
      activated carbonyl intermediate (enzyme-substrate complex) with the ethanolamine
      moiety of the preassembled GPI unit serving as a nucleophile. Other nucleophilic
      acceptors like hydrazine (HDZ) and hydroxylamine have been shown to be possible
      alternate substrates for GPI. Since GPI has yet to be purified, the use of
      readily available nucleophilic substitutes such as HDZ and hydroxylamine is a
      viable alternative to study COOH-terminal processing by the putative
      transamidase. As a first step in developing a soluble system to study this
      process, we have examined the amino acid requirements at the COOH terminus for
      the transamidation reaction using HDZ as the nucleophilic acceptor instead of
      GPI. The hydrazide-forming reaction shows identical amino acid requirement
      profiles to that of GPI anchor addition. Additionally, we have studied other
      parameters relating to the kinetics of the transamidation reaction in the context
      of rough microsomal membranes. The findings with HDZ provide further evidence for
      the transamidase nature of the enzyme and also provide a starting point for
      development of a soluble assay.

PMID- 8755509
TI  - Enhanced sensitivity of ubiquinone-deficient mutants of Saccharomyces cerevisiae
      to products of autoxidized polyunsaturated fatty acids.
AB  - Coenzyme Q (ubiquinone or Q) plays a well known electron transport function in
      the respiratory chain, and recent evidence suggests that the reduced form of
      ubiquinone (QH2) may play a second role as a potent lipid-soluble antioxidant. To
      probe the function of QH2 as an antioxidant in vivo, we have made use of a Q
      deficient strain of Saccharomyces cerevisiae harboring a deletion in the COQ3
      gene [Clarke, C. F., Williams, W. & Teruya, J. H. (1991) J. Biol. Chem. 266,
      16636-16644]. Q-deficient yeast and the wild-type parental strain were subjected
      to treatment with polyunsaturated fatty acids, which are prone to autoxidation
      and breakdown into toxic products. In this study we find that Q-deficient yeast
      are hypersensitive to the autoxidation products of linolenic acid and other
      polyunsaturated fatty acids. In contrast, the monounsaturated oleic acid, which
      is resistant to autoxidative breakdown, has no effect. The hypersensitivity of
      the coq3delta strains can be prevented by the presence of the COQ3 gene on a
      single copy plasmid, indicating that the sensitive phenotype results solely from
      the inability to produce Q. As a result of polyunsaturated fatty acid treatment,
      there is a marked elevation of lipid hydroperoxides in the coq3 mutant as
      compared with either wild-type or respiratory-deficient control strains. The
      hypersensitivity of the Q-deficient mutant can be rescued by the addition of
      butylated hydroxytoluene, alpha-tocopherol, or trolox, an aqueous soluble vitamin
      E analog. The results indicate that autoxidation products of polyunsaturated
      fatty acids mediate the cell killing and that QH2 plays an important role in vivo
      in protecting eukaryotic cells from these products.

PMID- 8755510
TI  - Interaction of the 82-kDa subunit of the vaccinia virus early transcription
      factor heterodimer with the promoter core sequence directs downstream DNA binding
      of the 70-kDa subunit.
AB  - The vaccinia virus early transcription factor (VETF), a heterodimeric protein
      composed of 82- and 70-kDa subunits, interacts with viral early promoters at both
      a sequence-specific core region upstream and a sequence-independent region
      downstream of the RNA start site. To determine the VETF subunit-promoter
      interactions, 32P-labeled DNA targets were chemically synthesized with uniquely
      positioned phosphorothioates to which azidophenacyl bromide moieties were
      coupled. After incubating the derivatized promoter with VETF and exposing the
      complex to 302-nm light, the protein was denatured and the individual subunits
      with or without covalently bound DNA were isolated with specific antiserum and
      analyzed by SDS/polyacrylamide gel electrophoresis. Using a set of 26 duplex
      probes, with uniquely positioned aryl azide moieties on the coding or template
      strands, we found that the 82-kDa subunit interacted primarily with the core
      region of the promoter, whereas the 70-kDa subunit interacted with the downstream
      region. Nucleotide substitutions in the core region that downregulate
      transcription affected the binding of both subunits: the 82-kDa subunit no longer
      exhibited specificity for upstream regions of the promoter but also bound to
      downstream regions, whereas the binding of the 70-kDa subunit was abolished even
      though the mutations were far upstream of its binding site. These results
      suggested mechanisms by which the interaction of the 82-kDa subunit with the core
      sequence directs binding of the 70-kDa subunit to DNA downstream.

PMID- 8755511
TI  - Glycerol-induced development of catalytically active conformation of Crotalus
      adamanteus L-amino acid oxidase in vitro.
AB  - The reconstitutable apoprotein of Crotalus adamanteus L-amino acid oxidase was
      prepared using hydrophobic interaction chromatography. After reconstitution with
      flavin adenine dinucleotide, the resulting protein was inactive, with a perturbed
      conformation of the flavin binding site. Subsequently, a series of cosolvent
      dependent compact intermediates was identified. The nearly complete activation of
      the reconstituted apoprotein and the restoration of its native flavin binding
      site was achieved in the presence of 50% glycerol. We provide evidence that in
      addition to a merely stabilizing effect of glycerol on native proteins, glycerol
      can also have a restorative effect on their compact equilibrium intermediates,
      and we suggest the hydrophobic effect as a dominating force in this in vitro
      assisted restorative process.

PMID- 8755512
TI  - Binding of thalidomide to alpha1-acid glycoprotein may be involved in its
      inhibition of tumor necrosis factor alpha production.
AB  - In addition to its well known sedative and teratogenic effects, thalidomide also
      possesses potent immunomodulatory and antiinflammatory activities, being most
      effective against leprosy and chronic graft-versus-host disease. The
      immunomodulatory activity of thalidomide has been ascribed to the selective
      inhibition of tumor necrosis factor alpha from monocytes. The molecular mechanism
      for the immunomodulatory effect of thalidomide remains unknown. To elucidate this
      mechanism, we synthesized an active photoaffinity label of thalidomide as a probe
      to identify the molecular target of the drug. Using the probe, we specifically
      labeled a pair of proteins of 43-45 kDa with high acidity from bovine thymus
      extract. Purification of these proteins and partial peptide sequence
      determination revealed them to be alpha1-acid glycoprotein (AGP). We show that
      the binding of thalidomide photoaffinity label to authentic human AGP is competed
      with both thalidomide and the nonradioactive photoaffinity label at
      concentrations comparable to those required for inhibition of production of tumor
      necrosis factor alpha from human monocytes, suggesting that AGP may be involved
      in the immunomodulatory activity of thalidomide.

PMID- 8755513
TI  - Complete structure of the human alpha-albumin gene, a new member of the serum
      albumin multigene family.
AB  - The nucleotide sequence of the human alpha-albumin gene, including 887 bp of the
      5'-flanking region and 1311 bp of the 3-flanking region (24,454 in total), was
      determined from three overlapping lambda phage clones. The sequence spans 22,256
      bp from the cap site to the polyadenylylation site, revealing a gene structure of
      15 exons separated by 14 introns. The methionine initiation codon ATG is within
      exon 1; the termination codon TGA is within exon 14. Exon 15 is entirely
      untranslated and contains the polyadenylylation signal AATAAA. The deduced
      polypeptide chain is composed of a 21-amino-acid leader peptide, followed by 578
      amino acids of the mature protein. There are seven repetitive DNA elements (Alu
      and Kpn) in the introns and 3-flanking region. The sizes of the 15 alpha-albumin
      exons match closely those of the albumin, alpha-fetoprotein, and vitamin D
      binding protein genes. The exons are symmetrically placed within the three
      domains of the individual proteins, and they share a characteristic codon
      splitting pattern that is conserved among members of the gene family. The results
      provide strong evidence that alpha-albumin belongs to, and most likely completes
      with, the serum albumin gene family. Based on structural similarity, alpha
      albumin appears to be most closely related to alpha-fetoprotein. The complete
      structure of this family of four tandemly linked genes provides a well
      characterized approximately 200 kb locus in the 4q subcentromeric region of the
      human genome.

PMID- 8755514
TI  - RNA binding by the Wilms tumor suppressor zinc finger proteins.
AB  - The Wilms tumor suppressor gene WT1 is implicated in the ontogeny of genito
      urinary abnormalities, including Denys-Drash syndrome and Wilms tumor of the
      kidney. WT1 encodes Kruppel-type zinc finger proteins that can regulate the
      expression of several growth-related genes, apparently by binding to specific DNA
      sites located within 5' untranslated leader regions as well as 5' promoter
      sequences. Both WT1 and a closely related early growth response factor, EGR1, can
      bind the same DNA sequences from the mouse gene encoding insulin-like growth
      factor 2 (Igf-2). We report that WT1, but not EGR1, can bind specific Igf-2
      exonic RNA sequences, and that the zinc fingers are required for this
      interaction. WT1 zinc finger 1, which is not represented in EGR1, plays a more
      significant role in RNA binding than zinc finger 4, which does have a counterpart
      in EGR1. Furthermore, the normal subnuclear localization of WT1 proteins is shown
      to be RNase, but not DNase, sensitive. Therefore, WT1 might, like the Kruppel
      type zinc finger protein TFIIIA, regulate gene expression by both transcriptional
      and posttranscriptional mechanisms.

PMID- 8755515
TI  - SMRT isoforms mediate repression and anti-repression of nuclear receptor
      heterodimers.
AB  - Transcriptional repression represents an important component in the regulation of
      cell differentiation and oncogenesis mediated by nuclear hormone receptors.
      Hormones act to relieve repression, thus allowing receptors to function as
      transcriptional activators. The transcriptional corepressor SMRT was identified
      as a silencing mediator for retinoid and thyroid hormone receptors. SMRT is
      highly related to another corepressor, N-CoR, suggesting the existence of a new
      family of receptor-interacting proteins. We demonstrate that SMRT is a ubiquitous
      nuclear protein that interacts with unliganded receptor heterodimers in mammalian
      cells. Furthermore, expression of the receptor-interacting domain of SMRT acts as
      an antirepressor, suggesting the potential importance of splicing variants as
      modulators of thyroid hormone and retinoic acid signaling.

PMID- 8755516
TI  - Expression cloning of the Golgi CMP-sialic acid transporter.
AB  - Translocation of nucleotide sugars across the membrane of the Golgi apparatus is
      a prerequisite for the synthesis of complex carbohydrate structures. While
      specific transport systems for different nucleotide sugars have been identified
      biochemically in isolated microsomes and Golgi vesicles, none of these transport
      proteins has been characterized at the molecular level. Chinese hamster ovary
      (CHO) mutants of the complementation group Lec2 exhibit a strong reduction in
      sialylation of glycoproteins and glycolipids due to a defect in the CMP-sialic
      acid transport system. By complementation cloning in the mutant 6B2, belonging to
      the Lec2 complementation group, we were able to isolate a cDNA encoding the
      putative murine Golgi CMP-sialic acid transporter. The cloned cDNA encodes a
      highly hydrophobic, multiple membrane spanning protein of 36.4 kDa, with
      structural similarity to the recently cloned ammonium transporters. Transfection
      of a hemagglutinin-tagged fusion protein into the mutant 6B2 led to Golgi
      localization of the hemagglutinin epitope. Our results, together with the
      observation that the cloned gene shares structural similarities to other recently
      cloned transporter proteins, strongly suggest that the isolated cDNA encodes the
      CMP-sialic acid transporter.

PMID- 8755517
TI  - HIV-1 nucleocapsid protein induces "maturation" of dimeric retroviral RNA in
      vitro.
AB  - After a retrovirus particle is released from the cell, the dimeric genomic RNA
      undergoes a change in conformation. We have previously proposed that this change,
      termed maturation of the dimer, is due to the action of nucleocapsid (NC) protein
      on the RNA within the virus particle. We now report that treatment of a 345-base
      synthetic fragment of Harvey sarcoma virus RNA with recombinant or synthetic HIV
      1 NC protein converts a less stable form of dimeric RNA to a more stable form.
      This phenomenon thus appears to reproduce the maturation of dimeric retroviral
      RNA in a completely defined system in vitro. To our knowledge, maturation of
      dimeric RNA within a retrovirus particle is the first example of action of an
      "RNA chaperone" protein in vivo. Studies with mutant NC proteins suggest that the
      activity depends upon basic amino acid residues flanking the N-terminal zinc
      finger and upon residues within the N-terminal finger, including an aromatic
      amino acid, but do not require the zinc finger structures themselves.

PMID- 8755518
TI  - A complex of nuclear proteins mediates SR protein binding to a purine-rich
      splicing enhancer.
AB  - A purine-rich splicing enhancer from a constitutive exon has been shown to shift
      the alternative splicing of calcitonin/CGRP pre-mRNA in vivo. Here, we
      demonstrate that the native repetitive GAA sequence comprises the optimal
      enhancer element and specifically binds a saturable complex of proteins required
      for general splicing in vitro. This complex contains a 37-kDa protein that
      directly binds the repetitive GAA sequence and SRp40, a member of the SR family
      of non-snRNP splicing factors. While purified SR proteins do not stably bind the
      repetitive GAA element, exogenous SR proteins become associated with the GAA
      element in the presence of nuclear extracts and stimulate GAA-dependent splicing.
      These results suggest that repetitive GAA sequences enhance splicing by binding a
      protein complex containing a sequence-specific RNA binding protein and a general
      splicing activator that, in turn, recruit additional SR proteins. This type of
      mechanism resembles the tra/tra-2-dependent recruitment of SR proteins to the
      Drosophila doublesex alternative splicing regulatory element.

PMID- 8755519
TI  - Interaction of the histone (H3-H4)2 tetramer of the nucleosome with positively
      supercoiled DNA minicircles: Potential flipping of the protein from a left- to a
      right-handed superhelical form.
AB  - We have studied the ability of the histone (H3-H4)2 tetramer, the central part of
      the nucleosome of eukaryotic chromatin, to form particles on DNA minicircles of
      negative and positive superhelicities, and the effect of relaxing these particles
      with topoisomerase I. The results show that even modest positive torsional stress
      from the DNA, and in particular that generated by DNA thermal fluctuations, can
      trigger a major, reversible change in the conformation of the particle. Neither a
      large excess of naked DNA, nor a crosslink between the two H3s prevented the
      transition from one form to the other. This suggested that during the transition,
      the histones neither dissociated from the DNA nor were even significantly
      reshuffled. Moreover, the particles reconstituted on negatively and positively
      supercoiled minicircles look similar under electron microscopy. These data agree
      best with a transition involving a switch of the wrapped DNA from a left- to a
      right-handed superhelix. It is further proposed, based on the left-handed overall
      superhelical conformation of the tetramer within the octamer [Arents, G.,
      Burlingame, R. W., Wang, B. C., Love, W. E. & Moudrianakis, E. N. (1991) Proc.
      Natl.Acad. Sci. USA 88, 10148-10152] that this change in DNA topology is mediated
      by a similar change in the topology of the tetramer itself, which may occur
      through a rotation (or a localized deformation) of the two H3-H4 dimers about
      their H3-H3 interface. Potential implications of this model for nucleosome
      dynamics in vivo are discussed.

PMID- 8755521
TI  - Internal molecular motions of bacteriorhodopsin: hydration-induced flexibility
      studied by quasielastic incoherent neutron scattering using oriented purple
      membranes.
AB  - Quasielastic incoherent neutron scattering from hydrogen atoms, which are
      distributed nearly homogeneously in biological molecules, allows the
      investigation of diffusive motions occurring on the pico- to nanosecond time
      scale. A quasielastic incoherent neutron scattering study was performed on the
      integral membrane protein bacteriorhodopsin (BR), which is a light-driven proton
      pump in Halobacterium salinarium. BR is embedded in lipids, forming patches in
      the cell membrane of the organism, which are the so called purple membranes
      (PMs). Measurements were carried out at room temperature on oriented PM-stacks
      hydrated at two different levels (low hydration, h = 0.03 g of D2O per g of PM;
      high hydration, h = 0.28 g of D2O per g of PM) using time-of-flight
      spectrometers. From the measured spectra, different diffusive components were
      identified and analyzed with respect to the influence of hydration. This study
      supports the idea that a decrease in hydration results in an appreciable decrease
      in internal molecular flexibility of the protein structure. Because it is known
      from studies on the function of BR that the pump activity is reduced if the
      hydration level of the protein is insufficient, we conclude that the observed
      diffusive motions are essential for the function of this protein. A detailed
      analysis and classification of the different kinds of diffusive motions,
      predominantly occurring in PMs under physiological conditions, is presented.

PMID- 8755520
TI  - DP-2, a heterodimeric partner of E2F: identification and characterization of DP-2
      proteins expressed in vivo.
AB  - E2F is a heterodimeric transcription factor that regulates the expression of
      genes at the G1/S boundary and is composed of two related but distinct families
      of proteins, E2F and DP. E2F/DP heterodimers form complexes with the
      retinoblastoma (Rb) protein, the Rb-related proteins p107 and p130, and
      cyclins/cdks in a cell cycle-dependent fashion in vivo. E2F is encoded by at
      least five closely related genes, E2F-1 through -5. Here we report studies of DP
      2, the second member of the DP family of genes. Our results indicate that (i) DP
      2 encodes at least five distinct mRNAs, (ii) a site of alternative splicing
      occurs within the 5' untranslated region of DP-2 mRNA, (iii) at least three DP-2
      related proteins (of 55, 48, and 43 kDa) are expressed in vivo, (iv) each of
      these proteins is phosphorylated, and (v) one DP-2 protein (43 kDa) carries a
      truncated amino terminus. Our data also strongly suggest that the 55-kDa DP-2
      related protein is a novel DP-2 isoform that results from alternative splicing.
      Thus, we conclude that DP-2 encodes a set of structurally, and perhaps
      functionally, distinct proteins in vivo.

PMID- 8755522
TI  - Influence of cisplatin intrastrand crosslinking on the conformation, thermal
      stability, and energetics of a 20-mer DNA duplex.
AB  - cis-Diamminedichloroplatinum(II) (cisplatin) is a widely used anticancer drug
      that binds to and crosslinks DNA. The major DNA adduct of the drug results from
      coordination of two adjacent guanine bases to platinum to form the intrastrand
      crosslink cis-[Pt(NH3)2[d(GpG)-N7(1), -N7(2)]] (cis-Pt-GG). In the present study,
      spectroscopic and calorimetric techniques were employed to characterize the
      influence of this crosslink on the conformation, thermal stability, and
      energetics of a site-specifically platinated 20-mer DNA duplex. CD spectroscopic
      and thermal denaturation data revealed that the crosslink alters the structure of
      the host duplex, consistent with a shift from a B-like to an A-like conformation;
      lowers its thermal stability by approximately 9 degrees C; and reduces its
      thermodynamic stability by 6.3 kcal/mol at 25 degrees C, most of which is
      enthalpic in origin; but it does not alter the two-state melting behavior
      exhibited by the parent, unmodified duplex, despite the significant crosslink
      induced changes noted above. The energetic consequences of the cis-Pt-GG
      crosslink are discussed in relation to the structural perturbations it induces in
      DNA and to how these crosslink-induced perturbations might modulate protein
      binding.

PMID- 8755523
TI  - Increased tricarboxylic acid cycle flux in rat brain during forepaw stimulation
      detected with 1H[13C]NMR.
AB  - NMR spectroscopy was used to test recent proposals that the additional energy
      required for brain activation is provided through nonoxidative glycolysis. Using
      localized NMR spectroscopic methods, the rate of C4-glutamate isotopic turnover
      from infused [1-(13)C]glucose was measured in the somatosensory cortex of rat
      brain both at rest and during forepaw stimulation. Analysis of the glutamate
      turnover data using a mathematical model of cerebral glucose metabolism showed
      that the tricarboxylic acid cycle flux [(V(TCA)] increased from 0.49 +/- 0.03 at
      rest to 1.48 +/- 0.82 micromol/g/min during stimulation (P < 0.01). The minimum
      fraction of C4-glutamate derived from C1-glucose was approximately 75%, and this
      fraction was found in both the resting and stimulated rats. Hence, the percentage
      increase in oxidative cerebral metabolic rate of glucose use (CMRglc) equals the
      percentage increases in V(TCA) and cerebral metabolic rate of oxygen consumption
      (CMRO2). Comparison with previous work for the same rat model, which measured
      total CMRglc [Ueki, M., Linn, F. & Hossman, K. A. (1988) J. Cereb. Blood Flow
      Metab. 8, 486-4941, indicates that oxidative CMRglc supplies the majority of
      energy during sustained brain activation.

PMID- 8755524
TI  - Sequence-specific recognition of cytosine C5 and adenine N6 DNA
      methyltransferases requires different deformations of DNA.
AB  - DNA methyltransferases modify specific cytosines and adenines within 2-6 bp
      recognition sequences. We used scanning force microscopy and gel shift analysis
      to show that M.HhaI, a cytosine C-5 DNA methyltransferase, causes only a 2 degree
      bend upon binding its recognition site. Our results are consistent with prior
      crystallographic analysis showing that the enzyme stabilizes an extrahelical base
      while leaving the DNA duplex otherwise unperturbed. In contrast, similar analysis
      of M.EcoRI, an adenine N6 DNA methyltransferase, shows an average bend angle of
      approximately 52 degrees. This distortion of DNA conformation by M.EcoRI is shown
      to be important for sequence-specific binding.

PMID- 8755525
TI  - Phytosulfokine, sulfated peptides that induce the proliferation of single
      mesophyll cells of Asparagus officinalis L.
AB  - Proliferation of dispersed plant cells in culture is strictly dependent on cell
      density, and cells in a low-density culture can only grow in the presence of
      conditioned medium (CM). No known plant hormones have been able to substitute for
      CM. To quantify the mitogenic activity of CM, we examined conditions for the
      assay system using mechanically dispersed mesophyll cells of Asparagus
      officinalis L. and established a highly sensitive bioassay method. By use of this
      method, the mitogenic activity of CM prepared from asparagus cells was
      characterized: it was heat-stable, susceptible to pronase digestion, and
      resistant to glycosidase treatment. On the basis of these results, the mitogenic
      activity in CM was purified 10(7)-fold by column chromatography, and two factors
      named phytosulfokine-alpha and -beta (PSK-alpha and PSK-beta) were obtained. By
      amino acid sequence analysis and mass spectrometry, the structures of these two
      factors were determined to be sulfated pentapeptide (H-Tyr(SO3H)-Ile-Tyr(SO3H)
      Thr-Gln-OH) and sulfated tetrapeptide (H-Tyr(SO3H)-Ile-Tyr(SO3H)-Thr-OH). PSK
      alpha and PSK-beta were prepared by chemical synthesis and enzymatic sulfation.
      The synthetic peptides exhibited the same activity as the natural factors,
      confirming the structure for PSK-alpha and PSK-beta mentioned above. This is the
      first elucidation of the structure of a conditioned medium factor required for
      the growth of low-density plant cell cultures.

PMID- 8755526
TI  - Cholesterol starvation induces differentiation of the intestinal parasite Giardia
      lamblia.
AB  - Giardia lamblia, like most human intestinal parasitic protozoa, sustains
      fundamental morphological and biochemical changes to survive outside the small
      intestine of its mammalian host by differentiating into an infective cyst.
      However, the stimulus that triggers this differentiation remains totally
      undefined. In this work, we demonstrate the induction of cyst formation in vitro
      when trophozoites are starved for cholesterol. Expression of cyst wall proteins
      was detected within encystation-specific secretory vesicles 90 min after the
      cells were placed in lipoprotein-deficient TYI-S-33 medium. Four cloned lines
      derived from two independent Giardia isolates were tested, and all formed cysts
      similarly. Addition of cholesterol, low density or very low density lipoproteins
      to the lipoprotein-deficient culture medium, inhibited the expression of cyst
      wall proteins, the generation of encystation-specific vesicles, and cyst wall
      biogenesis. In contrast, high density lipoproteins, phospholipids, bile salts, or
      fatty acids had little or no effect. These results indicate that cholesterol
      starvation is necessary and sufficient for the stimulation of Giardia encystation
      in vitro and, likely, in the intestine of mammalian hosts.

PMID- 8755527
TI  - Expression of cyclin D1 in epithelial tissues of transgenic mice results in
      epidermal hyperproliferation and severe thymic hyperplasia.
AB  - To study the involvement of cyclin D1 in epithelial growth and differentiation
      and its putative role as an oncogene in skin, transgenic mice were developed
      carrying the human cyclin D1 gene driven by a bovine keratin 5 promoter. As
      expected, all squamous epithelia including skin, oral mucosa, trachea, vaginal
      epithelium, and the epithelial compartment of the thymus expressed aberrant
      levels of cyclin D1. The rate of epidermal proliferation increased dramatically
      in transgenic mice, which also showed basal cell hyperplasia. However, epidermal
      differentiation was unaffected, as shown by normal growth arrest of newborn
      primary keratinocytes in response to high extracellular calcium. Moreover, an
      unexpected phenotype was observed in the thymus. Transgenic mice developed a
      severe thymic hyperplasia that caused premature death due to cardio-respiratory
      failure within 4 months of age. By 14 weeks, the thymi of transgenic mice
      increased in weight up to 40-fold, representing 10% of total body weight. The
      hyperplastic thymi had normal histology revealing a well-differentiated cortex
      and medulla, which supported an apparently normal T-cell developmental program
      based on the distribution of thymocyte subsets. These results suggest that
      proliferation and differentiation of epithelial cells are under independent
      genetic controls in these organs and that cyclin D1 can modulate epithelial
      proliferation without altering the initiation of differentiation programs. No
      spontaneous development of epithelial tumors or thymic lymphomas was perceived in
      transgenic mice during their first 8 months of life, although they continue under
      observation. This model provides in vivo evidence of the action of cyclin D1 as a
      pure mediator of proliferation in epithelial cells.

PMID- 8755528
TI  - Activation of RAC-protein kinase by heat shock and hyperosmolarity stress through
      a pathway independent of phosphatidylinositol 3-kinase.
AB  - RAC protein kinase (RAC-PK), a serine/threonine protein kinase containing a
      pleckstrin homology (PH) domain, was activated by cellular stress such as heat
      shock and hyperosmolarity. Wortmannin, which is known as a potent inhibitor of
      phosphatidylinositol 3-kinase and normally inhibits growth factor-induced
      activation of RAC-PK, did not suppress heat-shock induced activation of RAC-PK,
      indicating that this stress-induced activation of the kinase is not mediated by
      phosphatidylinositol 3-kinase. The PH domain was indispensable for stress-induced
      activation of RAC PK. In heat-treated cells, PKC delta, a member of the protein
      kinase C family, was found to associate with the PH domain of RAC-PK. This PKC
      subspecies was phosphorylated in vitro by RAC-PK. The results suggest that RAC-PK
      may play a role in the cellular response to stress through its PH domain.

PMID- 8755529
TI  - Hepatocyte growth factor is a coupling factor for osteoclasts and osteoblasts in
      vitro.
AB  - Hepatocyte growth factor (HGF), also known as scatter factor, is a powerful
      motogen, mitogen, and morphogen produced by cells of mesodermal origin, acting on
      epithelial and endothelial cells. Its receptor is the tyrosine kinase encoded by
      the c-MET protooncogene. We show that the HGF receptor is expressed by human
      primary osteoclasts, by osteoclast-like cell lines, and by osteoblasts. In both
      cell lineages, HGF stimulation triggers the receptor kinase activity and
      autophosphorylation. In osteoclasts, HGF receptor activation is followed by
      increase in intracellular Ca2+ concentration and by activation of the pp60c-Src
      kinase. HGF induces changes in osteoclast shape and stimulates chemotactic
      migration and DNA replication. Osteoblasts respond to HGF by entering the cell
      cycle, as indicated by stimulation of DNA synthesis. Interestingly, osteoclasts
      were found to synthesize and secrete biologically active HGF. These data strongly
      suggest the possibility of an autocrine regulation of the osteoclast by HGF and a
      paracrine regulation of the osteoblast by the HGF produced by the osteoclast.

PMID- 8755530
TI  - Monoclonal antibodies reveal receptor specificity among G-protein-coupled
      receptor kinases.
AB  - Guanine nucleotide-binding regulatory protein (G protein)-coupled receptor
      kinases (GRKs) constitute a family of serine/threonine kinases that play a major
      role in the agonist-induced phosphorylation and desensitization of G-protein
      coupled receptors. Herein we describe the generation of monoclonal antibodies
      (mAbs) that specifically react with GRK2 and GRK3 or with GRK4, GRK5, and GRK6.
      They are used in several different receptor systems to identify the kinases that
      are responsible for receptor phosphorylation and desensitization. The ability of
      these reagents to inhibit GRK- mediated receptor phosphorylation is demonstrated
      in permeabilized 293 cells that overexpress individual GRKs and the type 1A
      angiotensin II receptor. We also use this approach to identify the endogenous
      GRKs that are responsible for the agonist-induced phosphorylation of epitope
      tagged beta2- adrenergic receptors (beta2ARs) overexpressed in rabbit ventricular
      myocytes that are infected with a recombinant adenovirus. In these myocytes, anti
      GRK2/3 mAbs inhibit isoproterenol-induced receptor phosphorylation by 77%, while
      GRK4-6-specific mAbs have no effect. Consistent with the operation of a betaAR
      kinase-mediated mechanism, GRK2 is identified by immunoblot analysis as well as
      in a functional assay as the predominant GRK expressed in these cells.
      Microinjection of GRK2/3-specific mAbs into chicken sensory neurons, which have
      been shown to express a GRK3-like protein, abolishes desensitization of the
      alpha2AR-mediated calcium current inhibition. The intracellular inhibition of
      endogenous GRKs by mAbs represents a novel approach to the study of receptor
      specificities among GRKs that should be widely applicable to many G-protein
      coupled receptors.

PMID- 8755531
TI  - Isolation and characterization of mutant cell lines defective in transforming
      growth factor beta signaling.
AB  - To isolate and characterize effector molecules of the transforming growth factor
      beta (TGFbeta) signaling pathway we have used a genetic approach involving the
      generation of stable recessive mutants, defective in their TGFbeta signaling,
      which can subsequently be functionally complemented to clone the affected genes.
      We have generated a cell line derived from a hypoxanthine-guanine
      phosphoribosyltransferase negative (HPRT-) HT1080 clone that contains the
      selectable marker Escherichia coli guanine phosphoribosyltransferase (gpt) linked
      to a TGFbeta-responsive promoter. This cell line proliferates or dies in the
      appropriate selection medium in response to TGFbeta. We have isolated three
      distinct TGFbeta-unresponsive mutants following chemical mutagenesis. Somatic
      cell hybrids between pairs of individual TGFbeta-unresponsive clones reveal that
      each is in a distinct complementation group. Each mutant clone retains all three
      TGFbeta receptors yet fails to induce a TGFbeta-inducible luciferase reporter
      construct or TGFbeta-mediated plasminogen activator inhibitor-1 (PAI-1)
      expression. Two of the three have an attenuated TGFbeta-induced fibronectin
      response, whereas in the other mutant the fibronectin response is intact. These
      TGFbeta-unresponsive cells should allow selection and identification of signaling
      molecules through functional complementation.

PMID- 8755532
TI  - Real-time detection of the surface delivery of newly synthesized membrane
      proteins.
AB  - Newly synthesized membrane proteins travel from the Golgi complex to the cell
      surface in transport vesicles. We have exploited the ion channel properties of
      the nicotinic acetylcholine receptor (AChR) to observe in real time the
      constitutive delivery of newly synthesized AChR proteins to the plasma membrane
      in cultured muscle cells. Whole-cell voltage clamp was employed to monitor the
      current fluctuations induced by carbamylcholine upon the insertion into the
      plasma membrane of newly synthesized AChRs, following release from a 20 degrees C
      temperature block. We find that the transit of vesicles to the cell surface
      occurs within a few minutes after release of the block. The time course of
      electrical signals is consistent with many of the fusion events being
      instantaneous, although some appear to reveal the flickering of a fusion pore.
      AChR-containing vesicles can fuse individually or as conglomerates. Intracellular
      application of guanosine 5'-[gamma-thio]triphosphate inhibits the constitutive
      traffic of AChRs in most cells. Individual exocytotic vesicles carry between 10
      and 300 AChR molecules, suggesting that AChRs may be packed extremely densely.

PMID- 8755533
TI  - Nucleus-associated pools of Rna1p, the Saccharomyces cerevisiae Ran/TC4 GTPse
      activating protein involved in nucleus/cytosol transit.
AB  - Rna1p is the GTPase activating enzyme for Ran/TC4, a Ras-like GTPase necessary
      for nuclear/cytosolic exchange. Although most wild-type Rna1p is located in the
      cytosol, we found that the vast majority of the mutant Rna1-1p and, under
      appropriate physiological conditions, a small portion of the wild-type Rna1p
      cofractionate with yeast nuclei. Subnuclear fractionation studies show that most
      of the Rna1p is tightly associated with nuclear components, and that a portion of
      the active protein can be solubilized by treatments that fail to solubilize
      inactive Rna1-1p. To learn the precise nuclear locations of the Rna1 proteins, we
      studied their subcellular distributions in HeLa cells. By indirect immuno
      fluorescence we show that wild-type Rna1p has three subcellular locations. The
      majority of the protein is distributed throughout the cytosol, but a portion of
      the protein is nucleus-associated, located at both the cytosolic surface and
      within the nucleoplasm. Mutant Rna1-1p is found at the outer nuclear surface and
      in the cytosol. We propose that a small pool of the wild-type Rna1p is located in
      the nuclear interior, supporting the model that the same components of the
      Ran/TC4 GTPase cycle exist on both sides of the nuclear membrane.

PMID- 8755534
TI  - Transcriptionally active Stat1 is required for the antiproliferative effects of
      both interferon alpha and interferon gamma.
AB  - Type I (alpha, beta) and type II (gamma) interferons (IFNs) can restrict the
      growth of many cell types. INF-stimulated gene transcription, a key early event
      in IFN response, acts through the Janus kinase-signal transducers and activators
      of transcription pathway, in which both IFN-alpha and IFN-gamma activate the
      transcription factor Stat1. A cell line lacking Stat1 (U3A) was not growth
      arrested by IFN-alpha or IFN-gamma, and experiments were carried out with U3A
      cells permanently expressing normal or various mutant forms of Stat1 protein.
      Only cells in which complete Stat1 activity was available (Stat1alpha) were
      growth-inhibited by IFN-gamma. A mutant that supports 20-30% normal transcription
      did not cause growth restraint. In contrast, IFN-alpha growth restraint was
      imposed by cells producing Stat1beta, which lacks transcriptional activation
      potential. This parallels earlier results showing the truncated Stat1 can
      function in IFN-alpha gene activation. In addition to experiments on long-term
      cultured cells, we also found that wild-type primary mouse embryonic fibroblasts
      were inhibited by IFNs, but fibroblasts from Stat1-deficient mouse embryos were
      not inhibited by IFNs.

PMID- 8755535
TI  - Nucleotide-specific interaction of Ran/TC4 with nuclear transport factors NTF2
      and p97.
AB  - The use of permeabilized cell models to study nuclear protein import has led to
      the identification of cytosolic components of the import machinery, including the
      NLS receptor, p97, Ran/TC4, and nuclear transport factor 2 (NTF2). These proteins
      are required to reconstitute docking of transport ligand at the nuclear pore
      complex and subsequent translocation through the nuclear pore. However, a
      detailed molecular understanding of how these factors mediate protein import is
      lacking. Here we describe the results of solution and solid phase binding assays,
      which demonstrate that the small GTPase Ran/TC4 interacts directly with the
      cytosolic transport factors p97 and NTF2. By preloading recombinant Ran/TC4 with
      [gamma-32P]GTP or [3H]GDP, we show that the interactions with p97 and NTF2 are
      specific for the GTP- and GDP-bound forms, respectively. These data together with
      previous studies lead us to suggest that the interaction of the GTP-bound form of
      Ran/TC4 with p97 is linked to an early step in the nuclear protein import pathway
      and that the association of the GDP-bound form of Ran/TC4 with NTF2 helps define
      vectorial transport.

PMID- 8755536
TI  - Interaction of the protein import and folding machineries of the chloroplast.
AB  - We report the molecular cloning of import intermediate associated protein (IAP)
      100, a 100-kDa protein of the chloroplast protein import machinery of peas.
      IAP100 contains two potential alpha-helical transmembrane segments and also
      behaves like an integral membrane protein. It was localized to the inner
      chloroplast envelope membrane. Immunoprecipitation experiments using monospecific
      anti-IAP100 antibodies and a nonionic detergent-generated chloroplast lysate gave
      the following results. (i) The four integral membrane proteins of the outer
      chloroplast import machinery were not coprecipitated with IAP100 indicating that
      the inner and outer membrane import machineries are not coupled in isolated
      chloroplasts. (ii) the major protein that coprecipitated with IAP100 was
      identified as stromal chaperonin 60 (cpn60); the association of IAP100 and cpn60
      was specific and was abolished when immunoprecipitation was carried out in the
      presence of ATP. (iii) In a lysate from chloroplasts that had been preincubated
      for various lengths of time in an import reaction with radiolabeled precursor
      (pS) of the small subunit of Rubisco, we detected coimmunoprecipitation of
      IAP100, cpn60, and the imported mature form (S) of precursor. Relative to the
      time course of import, coprecipitation of S first increased and then decreased,
      consistent with a transient association of the newly imported S with the
      chaperonin bound to IAP100. These data suggest that IAP100 serves in recruiting
      chaperonin for folding of newly imported proteins.

PMID- 8755537
TI  - Inhibition of tumor progression by suppression of stress protein GRP78/BiP
      induction in fibrosarcoma B/C10ME.
AB  - Stress protein GRP78/BiP is highly induced in progressively growing tumors and
      has recently been shown to exert a protective role against lysis by cytotoxic T
      cells and tumor necrosis factor in vitro. This raises the question whether the in
      vitro observed protective function of GRP78/BiP translates into the in vivo
      situation in which tumors grow progressively, killing the host. Herein we report
      that molecular inhibition of GRP78/BiP induction in the fibrosarcoma B/C10ME,
      while not affecting in vitro cell proliferation, causes a dramatic increase in
      apoptotic cell death upon Ca2+ depletion of the endoplasmic reticulum. When
      B/C10ME cells incapable of inducing GRP78/BiP are injected into mice, tumors are
      initially formed that, however, regress presumably due to a cytotoxic T-cell
      response demonstrable by a strong in vitro response to the tumor with spleen
      cells of regressor mice. Since sensitivity to apoptosis is key to tumor
      rejection, these results may point to new approaches to the therapy of cancer via
      regulation of stress protein GRP78/BiP.

PMID- 8755539
TI  - Distinct desmocollin isoforms occur in the same desmosomes and show reciprocally
      graded distributions in bovine nasal epidermis.
AB  - The adhesive core of the desmosome is composed of cadherin-like glycoproteins of
      two families, desmocollins and desmogleins. Three isoforms of each are expressed
      in a tissue-specific and developmentally regulated pattern. In bovine nasal
      epidermis, the three desmocollin (Dsc) isoforms are expressed in overlapping
      domains; Dsc3 expression is strongest in the basal layer, while Dsc2 and Dsc1 are
      strongly expressed in the suprabasal layers. Herein we have investigated whether
      different isoforms are assembled into the same or distinct desmosomes by
      performing double immunogold labeling using isoform-specific antibodies directed
      against Dsc1 and Dsc3. The results show that individual desmosomes harbor both
      isoforms in regions where their expression territories overlap. Quantification
      showed that the ratio of the proteins in each desmosome altered gradually from
      basal to immediately suprabasal and upper suprabasal layers, labeling for Dsc1
      increasing and Dsc3 decreasing. Thus desmosomes are constantly modified as cells
      move up the epidermis, with continuing turnover of the desmosomal glycoproteins.
      Statistical analysis of the quantitative data showed a possible relationship
      between the distributions of the two isoforms. This gradual change in desmosomal
      composition may constitute a vertical adhesive gradient within the epidermis,
      having important consequences for cell positioning and differentiation.

PMID- 8755538
TI  - Isolation of the human PC6 gene encoding the putative host protease for HIV-1
      gp160 processing in CD4+ T lymphocytes.
AB  - Production of infectious HIV-1 virions is dependent on the processing of envelope
      glycoprotein gp160 by a host cell protease. The protease in human CD4+ T
      lymphocytes has not been unequivocally identified, yet members of the family of
      mammalian subtilisin-like protein convertases (SPCs), which are soluble or
      membrane-bound proteases of the secretory pathway, best fulfill the criteria.
      These proteases are required for proprotein maturation and cleave at paired basic
      amino acid motifs in numerous cellular and viral glycoprotein precursors, both in
      vivo and in vitro. To identify the gp160 processing protease, we have used
      reverse transcription-PCR and Northern blot analyses to ascertain the spectrum of
      SPC proteases in human CD4+ T cells. We have cloned novel members of the SPC
      family, known as the human PC6 genes. Two isoforms of the hPC6 protease are
      expressed in human T cells, hPC6A and the larger hPC6B. The patterns of SPC gene
      expression in human T cells has been compared with the furin-defective LoVo cell
      line, both of which are competent in the production of infectious HIV virions.
      This comparison led to the conclusion that the hPC6 gene products are the most
      likely candidates for the host cell protease responsible for HIV-1 gp160
      processing in human CD4+ T cells.

PMID- 8755540
TI  - P-OTX: a PIT-1-interacting homeodomain factor expressed during anterior pituitary
      gland development.
AB  - A novel OTX-related homeodomain transcription factor has been identified on the
      basis of its ability to interact with the transactivation domain of the pituitary
      specific POU domain protein, Pit-1. This factor, referred to as P-OTX (pituitary
      OTX-related factor), is expressed in primordial Rathke's pouch, oral epithelium,
      first bronchial arch, duodenum, and hindlimb. In the developing anterior
      pituitary, it is expressed in all regions from which cells with distinct
      phenotypes will emerge in the mature gland. P-OTX is able to independently
      activate and to synergize with Pit-1 on pituitary-specific target gene promoters.
      Therefore, P-OTX may subserve functions in generating both precursor and specific
      cell phenotypes in the anterior pituitary gland and in several other organs.

PMID- 8755541
TI  - Bioactivation of Mullerian inhibiting substance during gonadal development by a
      kex2/subtilisin-like endoprotease.
AB  - During male gonadal development Mullerian duct regression is mediated by the
      actions of the hormone Mullerian inhibiting substance (MIS), a member of the
      transforming growth factor beta superfamily. MIS is considered to be unique among
      members of this superfamily because bioactivation of MIS via proteolytic
      processing is hypothesized to occur at its target organ, the Mullerian duct. We
      find instead that the majority of MIS is processed and secreted from the
      embryonic testes as a complex in which the mature region remains noncovalently
      associated with the prodomain. In addition, we have identified two candidate
      endoproteases that are expressed in the testes and that may be capable of
      processing MIS in vivo. These kex2/subtilisin-like enzymes, PC5 and furin, are
      members of the proprotein convertase family that have been implicated in hormone
      bioactivation via proteolytic processing after dibasic amino acid cleavage
      recognition sites. Coexpression of PC5 and MIS in transfected mammalian cells
      results in efficient processing and bioactivation of MIS. Our results suggest
      that MIS is a natural substrate for PC5, thereby supporting a role for prohormone
      convertases in the activation of transforming growth factor beta-related hormones
      during development.

PMID- 8755542
TI  - Human fetal enterocytes in vitro: modulation of the phenotype by extracellular
      matrix.
AB  - The differentiation of small intestinal epithelial cells may require stimulation
      by microenvironmental factors in vivo. In this study, the effects of mesenchymal
      and luminal elements in nonmalignant epithelia] cells isolated from the human
      fetus were studied in vitro. Enterocytes from the human fetus were cultured and
      microenvironmental factors were added in stages, each stage more closely
      approximating the microenvironment in vivo. Four stages were examined: epithelial
      cells derived on plastic from intestinal culture and grown as a cell clone, the
      same cells grown on connective tissue support, primary epithelial explants grown
      on fibroblasts with a laminin base, and primary epithelial explants grown on
      fibroblasts and laminin with n-butyrate added to the incubation medium. The
      epithelial cell clone dedifferentiated when grown on plastic; however, the cells
      expressed cytokeratins and villin as evidence of their epithelial cell origin.
      Human connective tissue matrix from Engelbreth-Holm-Swarm sarcoma cells
      (Matrigel) modulated their phenotype: alkaline phosphatase activity increased,
      microvilli developed on their apical surface, and the profile of insulin-like
      growth factor binding proteins resembled that secreted by differentiated
      enterocytes. Epithelial cells taken directly from the human fetus as primary
      cultures and grown as explants on fibroblasts and laminin expressed greater
      specific enzyme activities in brush border membrane fractions than the cell
      clone. These activities were enhanced by the luminal molecule sodium butyrate.
      Thus the sequential addition of connective tissue and luminal molecules to
      nonmalignant epithelia] cells in vitro induces a spectrum of changes in the
      epithelial cell phenotype toward full differentiation.

PMID- 8755543
TI  - Exon shuffling and the origin of the mitochondrial targeting function in plant
      cytochrome c1 precursor.
AB  - Since most of the examples of "exon shuffling" are between vertebrate genes, the
      view is often expressed that exon shuffling is limited to the evolutionarily
      recent lineage of vertebrates. Although exon shuffling in plants has been
      inferred from the analysis of intron phases of plant genes [Long, M., Rosenberg,
      C. & Gilbert, W. (1995) Proc. Natl. Acad. Sci. USA 92, 12495-12499] and from the
      comparison of two functionally unknown sunflower genes [Domon, C. & Steinmetz, A.
      (1994) Mol. Gen. Genet. 244, 312-317], clear cases of exon shuffling in plant
      genes remain to be uncovered. Here, we report an example of exon shuffling in two
      important nucleus-encoded plant genes: cytosolic glyceraldehyde-3-phosphate
      dehydrogenase (cytosolic GAPDH or GapC) and cytochrome c1 precursor. The intron
      exon structures of the shuffled region indicate that the shuffling event took
      place at the DNA sequence level. In this case, we can establish a donor-recipient
      relationship for the exon shuffling. Three amino terminal exons of GapC have been
      donated to cytochrome c1, where, in a new protein environment, they serve as a
      source of the mitochondrial targeting function. This finding throws light upon an
      old important but unsolved question in gene evolution: the origin of presequences
      or transit peptides that generally exist in nucleus-encoded organelle genes.

PMID- 8755544
TI  - Substitution rate calibration of small subunit ribosomal RNA identifies
      chlorarachniophyte endosymbionts as remnants of green algae.
AB  - Chlorarachniophytes are amoeboid algae with chlorophyll a and b containing
      plastids that are surrounded by four membranes instead of two as in plants and
      green algae. These extra membranes form important support for the hypothesis that
      chlorarachniophytes have acquired their plastids by the ingestion of another
      eukaryotic plastid-containing alga. Chlorarachniophytes also contain a small
      nucleus-like structure called the nucleomorph situated between the two inner and
      the two outer membranes surrounding the plastid. This nucleomorph is a remnant of
      the endosymbiont's nucleus and encodes, among other molecules, small subunit
      ribosomal RNA. Previous phylogenetic analyses on the basis of this molecule
      provided unexpected and contradictory evidence for the origin of the
      chlorarachniophyte endosymbiont. We developed a new method for measuring the
      substitution rates of the individual nucleotides of small subunit ribosomal RNA.
      From the resulting substitution rate distribution, we derived an equation that
      gives a more realistic relationship between sequence dissimilarity and
      evolutionary distance than equations previously available. Phylogenetic trees
      constructed on the basis of evolutionary distances computed by this new method
      clearly situate the chlorarachniophyte nucleomorphs among the green algae.
      Moreover, this relationship is confirmed by transversion analysis of the
      Chlorarachnion plastid small subunit ribosomal RNA.

PMID- 8755545
TI  - The miniaturized nuclear genome of eukaryotic endosymbiont contains genes that
      overlap, genes that are cotranscribed, and the smallest known spliceosomal
      introns.
AB  - Chlorarachniophyte algae contain a complex, multi-membraned chloroplast derived
      from the endosymbiosis of a eukaryotic alga. The vestigial nucleus of the
      endosymbiont, called the nucleomorph, contains only three small linear
      chromosomes with a haploid genome size of 380 kb and is the smallest known
      eukaryotic genome. Nucleotide sequence data from a subtelomeric fragment of
      chromosome III were analyzed as a preliminary investigation of the coding
      capacity of this vestigial genome. Several housekeeping genes including U6 small
      nuclear RNA (snRNA), ribosomal proteins S4 and S13, a core protein of the
      spliceosome [small nuclear ribonucleoprotein (snRNP) E], and a cip-like protease
      (clpP) were identified. Expression of these genes was confirmed by combinations
      of Northern blot analysis, in situ hybridization, immunocytochemistry, and cDNA
      analysis. The protein-encoding genes are typically eukaryotic in overall
      structure and their messenger RNAs are polyadenylylated. A novel feature is the
      abundance of 18-, 19-, or 20-nucleotide introns; the smallest spliceosomal
      introns known. Two of the genes, U6 and S13, overlap while another two genes,
      snRNP E and clpP, are cotranscribed in a single mRNA. The overall gene
      organization is extraordinarily compact, making the nucleomorph a unique model
      for eukaryotic genomics.

PMID- 8755546
TI  - A common origin for woody Sonchus and five related genera in the Macaronesian
      islands: molecular evidence for extensive radiation.
AB  - Woody Sonchus and five related genera (Babcockia, Taeckholmia, Sventenia,
      Lactucosonchus, and Prenanthes) of the Macaronesian islands have been regarded as
      an outstanding example of adaptive radiation in angiosperms. Internal transcribed
      spacer region of the nuclear rDNA (ITS) sequences were used to demonstrate that,
      despite the extensive morphological and ecological diversity of the plants, the
      entire alliance in insular Macaronesia has a common origin. The sequence data
      place Lactucosonchus as sister group to the remainder of the alliance and also
      indicate that four related genera are in turn sister groups to subg.
      Dendrosonchus and Taeckholmia. This implies that the woody members of Sonchus
      were derived from an ancestor similar to allied genera now present on the Canary
      Islands. It is also evident that the alliance probably occurred in the Canary
      Islands during the late Miocene or early Pliocene. A rapid radiation of major
      lineages in the alliance is consistent with an unresolved polytomy near the base
      and low ITS sequence divergence. Increase of woodiness is concordant with other
      insular endemics and refutes the relictural nature of woody Sonchus in the
      Macaronesian islands.

PMID- 8755548
TI  - Molecular evidence that the asexual industrial fungus Trichoderma reesei is a
      clonal derivative of the ascomycete Hypocrea jecorina.
AB  - The relationship of the important cellulase producing asexual fungus Trichoderma
      reesei to its putative teleomorphic (sexual) ancestor Hypocrea jecorina and other
      species of the Trichoderma sect. Longibrachiatum was studied by PCR
      fingerprinting and sequence analyses of the nuclear ribosomal DNA region
      containing the internal transcribed spacers (ITS-1 and ITS-2) and the 5.8S rRNA
      gene. The differences in the corresponding ITS sequences allowed a grouping of
      anamorphic (asexual) species of Trichoderma sect. Longibrachiatum into
      Trichoderma longibrachiatum, Trichoderma pseudokoningii, and Trichoderma reesei.
      The sexual species Hypocrea schweinitzii and H. jecorina were also clearly
      separated from each other. H. jecorina and T. reesei exhibited identical
      sequences, suggesting close relatedness or even species identity. Intraspecific
      and interspecific variation in the PCR-fingerprinting patterns supported the
      differentiation of species based on ITS sequences, the grouping of the strains,
      and the assignment of these strains to individual species. The variations between
      T. reesei and H. jecorina were at the same order of magnitude as found between
      all strains of H. jecorina, but much lower than the observed interspecific
      variations. Identical ITS sequences and the high similarity of PCR-fingerprinting
      patterns indicate a very close relationship between T. reesei and H. jecorina,
      whereas differences of the ITS sequences and the PCR-fingerprinting patterns show
      a clear phylogenetic distance between T. reesei/H. jecorina and T.
      longibrachiatum. T. reesei is considered to be an asexual, clonal line derived
      from a population of the tropical ascomycete H. jecorina.

PMID- 8755547
TI  - The root of the universal tree and the origin of eukaryotes based on elongation
      factor phylogeny.
AB  - The genes for the protein synthesis elongation factors Tu (EF-Tu) and G (EF-G)
      are the products of an ancient gene duplication, which appears to predate the
      divergence of all extant organismal lineages. Thus, it should be possible to root
      a universal phylogeny based on either protein using the second protein as an
      outgroup. This approach was originally taken independently with two separate gene
      duplication pairs, (i) the regulatory and catalytic subunits of the proton
      ATPases and (ii) the protein synthesis elongation factors EF-Tu and EF-G.
      Questions about the orthology of the ATPase genes have obscured the former
      results, and the elongation factor data have been criticized for inadequate
      taxonomic representation and alignment errors. We have expanded the latter
      analysis using a broad representation of taxa from all three domains of life. All
      phylogenetic methods used strongly place the root of the universal tree between
      two highly distinct groups, the archaeons/eukaryotes and the eubacteria. We also
      find that a combined data set of EF-Tu and EF-G sequences favors placement of the
      eukaryotes within the Archaea, as the sister group to the Crenarchaeota. This
      relationship is supported by bootstrap values of 60-89% with various distance and
      maximum likelihood methods, while unweighted parsimony gives 58% support for
      archaeal monophyly.

PMID- 8755549
TI  - A strategy of exon shuffling for making large peptide repertoires displayed on
      filamentous bacteriophage.
AB  - It has been suggested that recombination and shuffling between exons has been a
      key feature in the evolution of proteins. We propose that this strategy could
      also be used for the artificial evolution of proteins in bacteria. As a first
      step, we illustrate the use of a self-splicing group I intron with inserted lox
      Cre recombination site to assemble a very large combinatorial repertoire (>
      10(11) members) of peptides from two different exons. Each exon comprised a
      repertoire of 10 random amino acids residues; after splicing, the repertoires
      were joined together through a central five-residue spacer to give a
      combinatorial repertoire of 25-residue peptides. The repertoire was displayed on
      filamentous bacteriophage by fusion to the pIII phage coat protein and selected
      by binding to several proteins, including beta-glucuronidase. One of the peptides
      selected against beta-glucuronidase was chemically synthesized and shown to
      inhibit the enzymatic activity (inhibition constant: 17 nM); by further exon
      shuffling, an improved inhibitor was isolated (inhibition constant: 7 nM). Not
      only does this approach provide the means for making very large peptide
      repertoires, but we anticipate that by introducing constraints in the sequences
      of the peptides and of the linker, it may be possible to evolve small folded
      peptides and proteins.

PMID- 8755550
TI  - Replication infidelity during a single cycle of Ty1 retrotransposition.
AB  - Retroviruses undergo a high frequency of genetic alterations during the process
      of copying their RNA genomes. However, little is known about the replication
      fidelity of other elements that transpose via reverse transcription of an RNA
      intermediate. The complete sequence of 29 independently integrated copies of the
      yeast retrotransposon Ty1 (173,043 nt) was determined, and the mutation rate
      during a single cycle of replication was calculated. The observed base
      substitution rate of 2.5 x 10(-5) bp per replication cycle suggests that this
      intracellular element can mutate as rapidly as retroviruses. The pattern and
      distribution of errors in the Ty1 genome is nonrandom and provides clues to
      potential in vivo molecular mechanisms of reverse transcriptase-mediated error
      generation, including heterogeneous RNase H cleavage of Ty1 RNA, addition of
      terminal nontemplated bases, and transient dislocation and realignment of primer
      templates. Overall, analysis of errors generated during Ty1 replication
      underscores the utility of a genetically tractable model system for the study of
      reverse transcriptase fidelity.

PMID- 8755551
TI  - The cyclin-dependent kinase inhibitor p40SIC1 imposes the requirement for Cln G1
      cyclin function at Start.
AB  - In yeast, commitment to cell division (Start) is catalyzed by activation of the
      Cdc28 protein kinase in late G1 phase by the Cln1, Cln2, and Cln3 G1 cyclins. The
      Clns are essential, rate-limiting activators of Start because cells lacking Cln
      function (referred to as cln-) arrest at Start and because CLN dosage modulates
      the timing of Start. At or shortly after Start, the development of B-type cyclin
      Clb-Cdc28 kinase activity and initiation of DNA replication requires the
      destruction of p40SIC1, a specific inhibitor of the Clb-Cdc28 kinases. I report
      here that cln cells are rendered viable by deletion of SIC1. Conversely, in cln1
      cln2 cells, which have low CLN activity, modest increases in SIC1 gene dosage
      cause inviability. Deletion of SIC1 does not cause a general bypass of Start
      since (cln-)sic1 cells remain sensitive to mating pheromone-induced arrest. Far1,
      a pheromone-activated inhibitor of Cln-Cdc28 kinases, is dispensable for arrest
      of (cln-)sic1 cells by pheromone, implying the existence of an alternate Far1
      independent arrest pathway. These observations define a pheromone-sensitive
      activity able to catalyze Start only in the absence of p40SIC1. The existence of
      this activity means that the B-type cyclin inhibitor p40SIC1 imposes the
      requirement for Cln function at Start.

PMID- 8755552
TI  - Highly efficient germ-line transmission of proviral insertions in zebrafish.
AB  - An important technology in model organisms is the ability to make transgenic
      animals. In the past, transgenic technology in zebrafish has been limited by the
      relatively low efficiency with which transgenes could be generated using either
      DNA microinjection or retroviral infection. Previous efforts to generate
      transgenic zebrafish with retroviral vectors used a pseudotyped virus with a
      genome based on the Moloney murine leukemia virus and the envelope protein of the
      vesicular stomatitis virus. This virus was injected into blastula-stage
      zebrafish, and 16% of the injected embryos transmitted proviral insertions to
      their offspring, with most founders transmitting a single insertion to
      approximately 2% of their progeny. In an effort to improve this transgenic
      frequency, we have generated pseudotyped viral stocks of two new Moloney-based
      genomes. These viral stocks have titers up to two orders of magnitude higher than
      that used previously. Injection of these viruses resulted in a dramatic increase
      in transgenic efficiency; over three different experiments, 83% (110/133) of the
      injected embryos transmitted proviral insertions to 24% of their offspring.
      Furthermore, founders made with one of the viruses transmitted an average of 11
      different insertions through their germ line. These results represent a 50- to
      100-fold improvement in the efficiency of generating transgenic zebrafish, making
      it now feasible for a single lab to rapidly generate tens to hundreds of
      thousands of transgenes. Consequently, large-scale insertional mutagenesis
      strategies, previously limited to invertebrates, may now be possible in a
      vertebrate.

PMID- 8755553
TI  - Retrotransposons of rice involved in mutations induced by tissue culture.
AB  - Five retrotransposon families of rice (Tos1-Tos5) have been reported previously.
      Here we report 15 new retrotransposon families of rice (Tos6-Tos20). In contrast
      to yeast and Drosophila retrotransposons, all of the rice retrotransposons
      examined appear inactive (or almost inactive) under normal growth conditions.
      Three of the rice retrotransposons (Tos10, Tos17, and Tos19) are activated under
      tissue culture conditions. The most active one, Tos17, was studied in detail. The
      copy number of Tos17 increased with prolonged culture period. In all of the
      plants regenerated from tissue cultures, including transgenic plants, 5 to 30
      transposed Tos17 copies were detected. The transcript of Tos17 was only detected
      under tissue culture conditions, indicating that the transposition of Tos17 is
      mainly regulated at the transcriptional level. To examine the target-site
      specificity of Tos17 transposition, sequences flanking transposed Tos17 copies
      were analyzed. At least four out of eight target sites examined are coding
      regions. Other target sites may also be in genes because two out of four were
      transcribed. The regenerated plants with Tos17-insertions in the phytochrome A
      gene and the S-receptor kinase-related gene were identified. These results
      indicate that activation of Tos17 is an important cause of tissue culture-induced
      mutations. Tissue culture-induced activation of Tos17 may be a useful tool for
      insertional mutagenesis and functional analysis of genes.

PMID- 8755554
TI  - Chronic, topical exposure to benzo[a]pyrene induces relatively high steady-state
      levels of DNA adducts in target tissues and alters kinetics of adduct loss.
AB  - Carcinogen-DNA adduct measurements may become useful biomarkers of effective dose
      and/or early effect. However, validation of this biomarker is required at several
      levels to ensure that human exposure and response are accurately reflected.
      Important in this regard is an understanding of the relative biomarker levels in
      target and nontarget organs and the response of the biomarker under the chronic,
      low-dose conditions to which humans are exposed. We studied the differences
      between single and chronic topical application of benzo[a]pyrene (BAP) on the
      accumulation and removal of BAP-DNA adducts in skin, lung, and liver. Animals
      were treated with BAP at 10, 25, or 50 nMol topically once or twice per week for
      as long as 15 weeks. Animals were sacrificed either at 24, 48, or 72 hr after the
      last dose at 1 and 30 treatments, and after 24 hr for all other treatment groups.
      Adduct levels increased with increasing dose, but the slope of the dose-response
      was different in each organ. At low doses, accumulation was linear in skin and
      lung, but at high doses the adduct levels in the lung increased dramatically at
      the same time when the levels in the skin reached apparent steady state. In the
      liver adduct, levels were lower than in target tissues and apparent steady-state
      adduct levels were reached rapidly, the maxima being independent of dose,
      suggesting that activating metabolism was saturated in this organ. Removal of
      adducts from skin, the target organ, was more rapid following single treatment
      than with chronic exposure. This finding is consistent with earlier data,
      indicating that some areas of the genome are more resistant to repair. Thus,
      repeated exposure and repair cycles would be more likely to cause an increase in
      the proportion of carcinogen-DNA adducts in repair-resistant areas of the genome.
      These findings indicate that single-dose experiments may underestimate the
      potential for carcinogenicity for compounds that follow this pattern.

PMID- 8755555
TI  - Sensitive detection of bacterial transcription initiation sites and
      differentiation from RNA processing sites in the pheromone-induced plasmid
      transfer system of Enterococcus faecalis.
AB  - A method was developed to detect 5' ends of bacterial RNAs expressed at low
      levels and to differentiate newly initiated transcripts from processed
      transcripts produced in vivo. The procedure involves use of RNA ligase to link a
      specific oligoribonucleotide to the 5' ends of cellular RNAs, followed by
      production of cDNA and amplification of the gene of interest by PCR. The method
      was used to identify the precise sites of transcription initiation within a 10-kb
      region of the pheromone-inducible conjugative plasmid pCF10 of Enterococcus
      faecalis. Results confirmed the 5' end of a very abundant, constitutively
      produced transcript (from prgQ) that had been mapped previously by primer
      extension and defined the initiation point of a less abundant, divergently
      transcribed message (from prgX). The method also showed that the 5' end of a
      pheromone-inducible transcript (prgB) that had been mapped by primer extension
      was generated by processing rather than new initiation. In addition, the results
      provided evidence for two promoters, 3 and 5 kb upstream of prgB, and indicated
      that only the transcripts originating 5 kb upstream may be capable of extending
      to prgB.

PMID- 8755556
TI  - Identification of a pathogenicity island required for Salmonella survival in host
      cells.
AB  - We have identified a region unique to the Salmonella typhimurium chromosome that
      is essential for virulence in mice. This region harbors at least three genes: two
      (spiA and spiB) encode products that are similar to proteins found in type III
      secretion systems, and a third (spiR) encodes a putative regulator. A strain with
      a mutation in spiA was unable to survive within macrophages but displayed wild
      type levels of epithelial cell invasion. The culture supernatants of the spi
      mutants lacked a modified form of flagellin, which was present in the supernatant
      of the wild-type strain. This suggests that the Spi secretory apparatus exports a
      protease, or a protein that can alter the activity of a secreted protease. The
      "pathogenicity island" harboring the spi genes may encode the virulence
      determinants that set Salmonella apart from other enteric pathogens.

PMID- 8755557
TI  - Cellular strategies for accommodating replication-hindering adducts in DNA:
      control by the SOS response in Escherichia coli.
AB  - The replication of double-stranded plasmids containing a single adduct was
      analyzed in vivo by means of a sequence heterology that marks the two DNA
      strands. The single adduct was located within the sequence heterology, making it
      possible to distinguish trans-lesion synthesis (TLS) events from damage avoidance
      events in which replication did not proceed through the lesion. When the SOS
      system of the host bacteria is not induced, the C8-guanine adduct formed by the
      carcinogen N-2-acetylaminofluorene (AAF) yields less than 1% of TLS events,
      showing that replication does not readily proceed through the lesion. In
      contrast, the deacetylated adduct N-(deoxyguanosin-8-yl)-2-aminofluorene yields
      approximately 70% of TLS events under both SOS-induced and uninduced conditions.
      These results for TLS in vivo are in good agreement with the observation that AAF
      blocks DNA replication in vitro, whereas aminofluorene does so only weakly.
      Induction of the SOS response causes an increase in TLS events through the AAF
      adduct (approximately 13%). The increase in TLS is accompanied by a proportional
      increase in the frequency of AAF-induced frameshift mutations. However, the
      polymerase frameshift error rate per TLS event was essentially constant
      throughout the SOS response. In an SOS-induced delta umuD/C strain, both US
      events and mutagenesis are totally abolished even though there is no decrease in
      plasmid survival. Error-free replication evidently proceeds efficiently by means
      of the damage avoidance pathway. We conclude that SOS mutagenesis results from
      increased TLS rather than from an increased frameshift error rate of the
      polymerase.

PMID- 8755558
TI  - Minimal definition of the imprinting center and fixation of chromosome 15q11-q13
      epigenotype by imprinting mutations.
AB  - Patients with disorders involving imprinted genes such as Angelman syndrome (AS)
      and Prader-Willi syndrome (PWS) can have a mutation in the imprinting mechanism.
      Previously, we identified an imprinting center (IC) within chromosome 15q11-ql3
      and proposed that IC mutations block resetting of the imprint, fixing on that
      chromosome the parental imprint (epigenotype) on which the mutation arose. We now
      describe four new microdeletions of the IC, the smallest (6 kb) of which
      currently defines the minimal region sufficient to confer an AS imprinting
      mutation. The AS deletions all overlap this minimal region, centromeric to the
      PWS microdeletions, which include the first exon of the SNRPN gene. None of five
      genes or transcripts in the 1.0 Mb vicinity of the IC (ZNF127, SNRPN, PAR-5, IPW,
      and PAR-1), each normally expressed only from the paternal allele, was expressed
      in cells from PWS imprinting mutation patients. In contrast, AS imprinting
      mutation patients show biparental expression of SNRPN and IPW but must lack
      expression of the putative AS gene 250-1000 kb distal of the IC. These data
      strongly support a model in which the paternal chromosome of these PWS patients
      carries an ancestral maternal epigenotype, and the maternal chromosome of these
      AS patients carries an ancestral paternal epigenotype. The IC therefore functions
      to reset the maternal and paternal imprints throughout a 2-Mb imprinted domain
      within human chromosome 15q11-q13 during gametogenesis.

PMID- 8755559
TI  - A Ds insertion alters the nuclear localization of the maize transcriptional
      activator R.
AB  - The R-sc gene of maize is a member of the R gene family of transcriptional
      activators that regulate anthocyanin biosynthesis. A derivative of R-sc, r-m9
      conditions a reduced level of aleurone pigmentation due to the presence of a 2.1
      kb Ds insertion near the 3' end of the coding region. Excision of Ds from r-m9
      leaves a 7-bp insertion in the darker but still mutant v24 derivative. Both the 7
      bp insertion in v24 and the 2.1-kb Ds in r-m9 are predicted to truncate their
      respective R proteins proximal to the carboxyl terminus, which was shown
      previously to contain one of three nuclear localization sequences. We find that
      the reduced expression of r-m9 and v24 are not due to mRNA or protein
      instability, but most likely reflect the inefficient localization of truncated R
      proteins to the nucleus. To our knowledge this is the first example of a
      transposable element insertion that alters gene expression by affecting nuclear
      localization. In addition, our data indicate that the carboxyl terminus of the R
      protein is far more important than previously suspected and illustrates the
      utility of natural mutations for defining functional domains in proteins.

PMID- 8755560
TI  - Phenotypic and physiologic characterization of transgenic mice expressing
      interleukin 4 in the lung: lymphocytic and eosinophilic inflammation without
      airway hyperreactivity.
AB  - To investigate the contribution of interleukin-4 (IL-4) to airway inflammation in
      vivo and to explore directly its relationship to airway reactivity, we created
      transgenic mice in which the murine cDNA for IL-4 was regulated by the rat Clara
      cell 10 protein promoter. Expression was detected only in the lung and not in
      thymus, heart, liver, spleen, kidney, or uterus. The expression of IL-4 elicited
      hypertrophy of epithelial cells of the trachea, bronchi, and bronchioles.
      Hypertrophy is due, at least in part, to the accumulation of mucus glycoprotein.
      Histologic examination of parenchyma revealed multinucleated macrophages and
      occasional islands of cells consisting largely of eosinophils or lymphocytes.
      Analysis of lung lavage fluid revealed the presence of a leukocytic infiltrate
      consisting of lymphocytes, neutrophils and eosinophils. Mice expressing IL-4 had
      greater baseline airway resistance but did not demonstrate hyperreactivity to
      methacholine. Thus, the expression of IL-4 selectively within the lung elicits an
      inflammatory response characterized by epithelial cell hypertrophy, and the
      accumulation of macrophages, lymphocytes, eosinophils, and neutrophils without
      resulting in an alteration in airway reactivity to inhaled methacholine.

PMID- 8755561
TI  - An antibody-interleukin 2 fusion protein overcomes tumor heterogeneity by
      induction of a cellular immune response.
AB  - Antibody-based therapies for cancer rely on the expression of defined antigens on
      neoplastic cells. However, most tumors display heterogeneity in the expression of
      such antigens. We demonstrate here that antibody-targeted interleukin 2 delivery
      overcomes this problem by induction of a host immune response.
      Immunohistochemical analysis demonstrated that the antibody-interleukin 2 fusion
      protein-induced eradication of established tumors is mediated by host immune
      cells, particularly CD8+ T cells. Because of this cellular immune response,
      antibody-directed interleukin 2 therapy is capable to address established
      metastases displaying substantial heterogeneity in expression of the targeted
      antigen. This effector mechanism further enables the induction of partial
      regressions of large subcutaneous tumors that exceeded more than 5% of the body
      weight. These observations indicate that antibody-directed cytokine delivery
      offers an effective new tool for cancer therapy.

PMID- 8755562
TI  - Expression of hyaluronidase by tumor cells induces angiogenesis in vivo.
AB  - Hyaluronic acid is a proteoglycan present in the extracellular matrix and is
      important for the maintenance of tissue architecture. Depolymerization of
      hyaluronic acid may facilitate tumor invasion. In addition, oligosaccharides of
      hyaluronic acid have been reported to induce angiogenesis. We report here that a
      hyaluronidase similar to the one on human sperm is expressed by metastatic human
      melanoma, colon carcinoma, and glioblastoma cell lines and by tumor biopsies from
      patients with colorectal carcinomas, but not by tissues from normal colon.
      Moreover, angiogenesis is induced by hyaluronidase+ tumor cells but not
      hyaluronidase- tumor cells and can be blocked by an inhibitor of hyaluronidase.
      Tumor cells thus use hyaluronidase as one of the "molecular saboteurs" to
      depolymerize hyaluronic acid to facilitate invasion. As a consequence, breakdown
      products of hyaluronic acid can further promote tumor establishment by inducing
      angiogenesis. Hyaluronidase on tumor cells may provide a target for anti
      neoplastic drugs.

PMID- 8755563
TI  - Identification and characterization of an alternative cytotoxic T lymphocyte
      associated protein 4 binding molecule on B cells.
AB  - To determine whether alternative cytotoxic T lymphocyte-associated protein 4
      (CTLA4) binding proteins exist on B cells, we constructed (i) mCTLA4hIgG
      consisting of the extracellular region of a mouse CTLA4 molecule and the Fc
      portion of a human IgG1 molecule and (ii) PYAAhIgG, a mutant mCTLA4hIgG, having
      two amino acid substitutions on the conserved MYPPPY motif in the complementarity
      determining region 3-like region and lacking detectable binding to both B7-1 and
      B7-2 molecules. Using these fusion proteins (mCTLA4hIgG and PYAAhIgG), we
      demonstrated that a mouse immature B-cell line, WEHI231 cells, expressed
      alternative CTLA4 binding molecules (ACBMs) that were distinct from both B7-1 and
      B7-2. ACBMs were 130-kDa disulfide-linked proteins. More importantly, ACBMs were
      able to provide costimulatory signal for T-cell proliferation in the presence of
      anti-CD3 monoclonal antibodies. In addition, we demonstrated that more than 20%
      of B220+ cells obtained from normal mouse spleen expressed ACBMs.

PMID- 8755564
TI  - A novel strategy for generating monoclonal antibodies from single, isolated
      lymphocytes producing antibodies of defined specificities.
AB  - We report a novel approach to the generation of monoclonal antibodies based on
      the molecular cloning and expression of immunoglobulin variable region cDNAs
      generated from single rabbit or murine lymphocytes that were selected for the
      production of specific antibodies. Single cells secreting antibodies for a
      specific peptide either from gp116 of the human cytomegalovirus or from gp120 of
      HIV-1 or for sheep red blood cells were selected using antigen-specific hemolytic
      plaque assays. Sheep red blood cells were coated with specific peptides in a
      procedure applicable to any antigen that can be biotinylated. Heavy- and light
      chain variable region cDNAs were rescued from single cells by reverse
      transcription-PCR and expressed in the context of human immunoglobulin constant
      regions. These chimeric murine and rabbit monoclonal antibodies replicated the
      target specificities of the original antibody-forming cells. The selected
      lymphocyte antibody method exploits the in vivo mechanisms that generate high
      affinity antibodies. This method can use lymphocytes from peripheral blood, can
      exploit a variety of procedures that identify individual lymphocytes producing a
      particular antibody, and is applicable to the generation of monoclonal antibodies
      from many species, including humans.

PMID- 8755565
TI  - An essential regulatory role for macrophage migration inhibitory factor in T-cell
      activation.
AB  - The protein known as macrophage migration inhibitory factor (MIF) was one of the
      first cytokines to be discovered and was described 30 years ago to be a T-cell
      derived factor that inhibited the random migration of macrophages in vitro. A
      much broader role for MIF has emerged recently as a result of studies that have
      demonstrated it to be released from the anterior pituitary gland in vivo. MIF
      also is the first protein that has been identified to be secreted from
      monocytes/macrophages upon glucocorticoid stimulation. Once released, MIF acts to
      "override" or counter-regulate the suppressive effects of glucocorticoids on
      macrophage cytokine production. We report herein that MIF plays an important
      regulatory role in the activation of T cells induced by mitogenic or antigenic
      stimuli. Activated T cells produce MIF and neutralizing anti-MIF antibodies
      inhibit T-cell proliferation and interleukin 2 production in vitro, and suppress
      antigen-driven T-cell activation and antibody production in vivo. T cells also
      release MIF in response to glucocorticoid stimulation and MIF acts to override
      glucocorticoid inhibition of T-cell proliferation and interleukin 2 and
      interferon gamma production. These studies indicate that MIF acts in concert with
      glucocorticoids to control T-cell activation and assign a previously unsuspected
      but critical role for MIF in antigen-specific immune responses.

PMID- 8755566
TI  - Peptide vaccination can lead to enhanced tumor growth through specific T-cell
      tolerance induction.
AB  - Vaccination with synthetic peptides representing cytotoxic T lymphocyte (CTL)
      epitopes can lead to a protective CTL-mediated immunity against tumors or
      viruses. We now report that vaccination with a CTL epitope derived from the human
      adenovirus type 5 E1A-region (Ad5E1A234-243), which can serve as a target for
      tumor-eradicating CTL, enhances rather than inhibits the growth of Ad5E1A
      expressing tumors. This adverse effect of peptide vaccination was rapidly evoked,
      required low doses of peptide (10 micrograms), and was achieved by a mode of
      peptide delivery that induces protective T-cell-mediated immunity in other
      models. Ad5E1A-specific CTL activity could no longer be isolated from mice after
      injection of Ad5E1A-peptide, indicating that tolerization of Ad5E1A-specific CTL
      activity causes the enhanced tumor outgrowth. In contrast to peptide vaccination,
      immunization with adenovirus, expressing Ad5E1A, induced Ad5E1A-specific immunity
      and prevented the outgrowth of Ad5E1A-expressing tumors. These results show that
      immunization with synthetic peptides can lead to the elimination of anti-tumor
      CTL responses. These findings are important for the design of safe peptide-based
      vaccines against tumors, allogeneic organ transplants, and T-cell-mediated
      autoimmune diseases.

PMID- 8755567
TI  - 1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing
      encephalomyelitis, a model of multiple sclerosis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease believed
      to be a model for the human disease multiple sclerosis (MS). Induced by
      immunizing B10.PL mice with myelin basic protein (MBP), EAE was completely
      prevented by the administration of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. 1,25
      (OH)2D3 could also prevent the progression of EAE when administered at the
      appearance of the first disability symptoms. Withdrawal of 1,25-(OH)2D3 resulted
      in a resumption of the progression of EAE. Thus, the block by 1,25-(OH)2D3 is
      reversible. A deficiency of vitamin D resulted in an increased susceptibility to
      EAE. Thus, 1,25-(OH)2D3 or its analogs are potentially important for treatment of
      MS.

PMID- 8755568
TI  - Evidence for a preformed transducer complex organized by the B cell antigen
      receptor.
AB  - The B cell antigen receptor (BCR) consists of the membrane-bound immunoglobulin
      (mIg) molecule and the Ig-alpha/Ig-beta heterodimer, which functions as signaling
      subunit of the receptor. Stimulation of the BCR activates protein tyrosine
      kinases (PTKs) that phosphorylate a number of substrate proteins, including the
      Ig-alpha/Ig-beta heterodimer of the BCR itself. How the PTKs become activated
      after BCR engagement is not known at present. Here, we show that BCR-negative
      J558L cells treated with the protein tyrosine phosphatase inhibitor
      pervanadate/H2O2 display only a weak substrate phosphorylation. However, in BCR
      positive transfectants of J558L, treatment with pervanadate/H2O2 induces a strong
      phosphorylation of several substrate proteins. Treatment with pervanadate/H2O2
      does not result in receptor crosslinking, yet the pattern of protein
      phosphorylation is similar to that observed after BCR stimulation by antigen. The
      response requires cellular integrity because tyrosine phosphorylation of most
      substrates is not visible in cell lysates. Cells that express a BCR containing an
      Ig-alpha subunit with a mutated immunoreceptor tyrosine-based activation motif
      display a delayed response. The data suggest that, once expressed on the surface,
      the BCR organizes protein tyrosine phosphatases, PTKs, and their substrates into
      a transducer complex that can be activated by pervanadate/H202 in the absence of
      BCR crosslinking. Assembly of this preformed complex seems to be a prerequisite
      for BCR-mediated signal transduction.

PMID- 8755569
TI  - Gene-targeted deletion and replacement mutations of the T-cell receptor beta
      chain enhancer: the role of enhancer elements in controlling V(D)J recombination
      accessibility.
AB  - To assess the role of transcriptional enhancers in regulating accessibility of
      the T-cell receptor beta-chain (TCRbeta) locus, we generated embryonic stem cell
      lines in which a single allelic copy of the endogenous TCRbeta enhancer (Ebeta)
      was either deleted or replaced with the immunoglobulin heavy-chain intronic
      enhancer. We assayed the effects of these mutations on activation of the TCRbeta
      locus in normal T- and B-lineage cells by RAG-2 (recombination-activating gene 2)
      deficient blastocyst complementation. We found that Ebeta is required for
      rearrangement and germ-line transcription of the TCRbeta locus in T-lineage
      cells. In the absence of Ebeta, the heavy-chain intronic enhancer partially
      supported joining region beta-chain rearrangement in T- but not in B-lineage
      cells. However, ability of the heavy-chain intronic enhancer to induce
      rearrangements was blocked by linkage to an expressed neomycin-resistance gene
      (neo(r)). These results demonstrate a critical role for Ebeta in promoting
      accessibility of the TCRbeta locus and suggest that additional negative elements
      may cooperate to further modulate this process.

PMID- 8755570
TI  - Deletion of the mouse T-cell receptor beta gene enhancer blocks alphabeta T-cell
      development.
AB  - Intrathymic T-cell development requires temporally regulated rearrangement and
      expression of T-cell receptor (TCR) genes. To assess the role of the TCR beta
      gene transcriptional enhancer (Ebeta) in this process, mouse strains in which
      Ebeta is deleted were generated using homologous recombination techniques. We
      report that mice homozygous for the Ebeta deletion, whether a selectable marker
      gene is present or not, show a block in alphabeta T-cell development at the CD4
      CD8- double-negative cell stage, whereas the number of gammadelta+ T cells is
      normal, few CD4+CD8+ double-positive thymocytes and no alphabeta+ T cells are
      produced. DNA-PCR and RNA-PCR analyses of thymic cells from homozygous mutants
      showed no evidence of TCR beta gene rearrangement although germ-line Vbeta
      transcripts were detected at a low level, in heterozygous T cells, the targeted
      allele is not rearranged. Thus, deletion of Ebeta totally prevents rearrangement,
      but not transcription, of the targeted beta locus. These data formally establish
      the critical role played by Ebeta in cis-activation of the TCR beta locus for
      V(D)J recombination during alphabeta T-cell development.

PMID- 8755571
TI  - Pore-forming toxins trigger shedding of receptors for interleukin 6 and
      lipopolysaccharide.
AB  - Cleavage of membrane-associated proteins with the release of biologically active
      macromolecules is an emerging theme in biology. However, little is known about
      the nature and regulation of the involved proteases or about the physiological
      inducers of the shedding process. We here report that rapid and massive shedding
      of the interleukin 6 receptor (IL-6R) and the lipopolysaccharide receptor (CD14)
      occurs from primary and transfected cells attacked by two prototypes of pore
      forming bacterial toxins, streptolysin O and Escherichia coli hemolysin. Shedding
      is not induced by an streptolysin O toxin mutant which retains cell binding
      capacity but lacks pore-forming activity. The toxin-dependent cleavage site of
      the IL-6R was mapped to a position close to, but distinct from, that observed
      after stimulation with phorbol myristate acetate. Soluble IL-6R that was shed
      from toxin-treated cells bound its ligand and induced an IL-6-specific signal in
      cells that primarily lacked the IL-6R. Transsignaling by soluble IL-6R and
      soluble CD14 is known to dramatically broaden the spectrum of host cells for IL-6
      and lipopolysaccharide, and is thus an important mechanism underlying their
      systemic inflammatory effects. Our findings uncover a novel mechanism that can
      help to explain the long-range detrimental action of pore-forming toxins in the
      host organism.

PMID- 8755572
TI  - Purification and molecular cloning of an inducible gram-negative bacteria-binding
      protein from the silkworm, Bombyx mori.
AB  - A 50-kDa hemolymph protein, having strong affinity to the cell wall of Gram(-)
      bacteria, was purified from the hemolymph of the silkworm, Bombyx mori. The cDNA
      encoding this Gram(-) bacteria-binding protein (GNBP) was isolated from an
      immunized silkworm fat body cDNA library and sequenced. Comparison of the deduced
      amino acid sequence with known sequences revealed that GNBP contained a region
      displaying significant homology to the putative catalytic region of a group of
      bacterial beta-1,3 glucanases and beta-1,3-1,4 glucanases. Silkworm GNBP was also
      shown to have amino acid sequence similarity to the vertebrate lipopolysaccharide
      receptor CD14 and was recognized specifically by a polygonal anti-CD14 antibody.
      Northern blot analysis showed that GNBP was constitutively expressed in fat body,
      as well as in cuticular epithelial cells of naive silkworms. Intense
      transcription was, however, rapidly induced following a cuticular or hemoceolien
      bacterial challenge. An mRNA that hybridized with GNBP cDNA was also found in the
      l(2)mbn immunocompetent Drosophila cell line. These observations suggest that
      GNBP is an inducible acute phase protein implicated in the immune response of the
      silkworm and perhaps other insects.

PMID- 8755573
TI  - Constitutive receptor activation by Crouzon syndrome mutations in fibroblast
      growth factor receptor (FGFR)2 and FGFR2/Neu chimeras.
AB  - Crouzon syndrome is an autosomal dominant condition primarily characterized by
      craniosynostosis. This syndrome has been associated with a variety of amino acid
      point mutations in the extracellular domain of fibroblast growth factor receptor
      2 (FGFR2). FGFR2/Neu chimeras were generated by substituting the extracellular
      domain of Neu with that of FGFR2 containing the following Crouzon mutations: Tyr
      340-->His; Cys-342-->Tyr; Cys-342-->Arg; Cys-342-->Ser; Ser-354-->Cys: and
      delta17 (deletion of amino acids 345-361). Each of the mutant chimeric FGFR2/Neu
      constructs stimulated focus formation in NIH 3T3 cells, indicating that Crouzon
      mutations can stimulate signal transduction through a heterologous receptor
      tyrosine kinase. In vitro kinase assay results indicate that FGFR2 receptors
      containing Crouzon mutations have increased tyrosine kinase activity and, when
      analyzed under nonreducing conditions, exhibited disulfide-bonded dimers. Thus
      the human developmental abnormality Crouzon syndrome arises from constitutive
      activation of FGFR2 due to aberrant intermolecular disulfide-bonding. These
      results together with our earlier observation that achondroplasia results from
      constitutive activation of the related receptor FGFR3, leads to the prediction
      that other malformation syndromes attributed to FGFRs, such as Pfeiffer syndrome
      and Thanatophoric dysplasia, also arise from constitutive receptor activation.

PMID- 8755574
TI  - Transgenic expression of PML/RARalpha impairs myelopoiesis.
AB  - The translocation found in acute promyelocytic leukemia rearranges the
      promyelocytic leukemia gene (PML) on chromosome 15 with the retinoic acid
      receptor alpha (RARalpha) on chromosome 17. This yields a fusion transcript,
      PML/RARalpha, a transcription factor with reported dominant negative functions in
      the absence of hormone. Clinical remissions induced with all-trans retinoic acid
      (RA) treatment in acute promyelocytic leukemia are linked to PML/RARalpha
      expression in leukemic cells. To evaluate the PML/RARalpha role in myelopoiesis,
      transgenic mice expressing PML/RARalpha were engineered. A full-length
      PML/RARalpha cDNA driven by the CD11b promoter was expressed in transgenic mice.
      Expression was confirmed in the bone marrow with a reverse transcription PCR
      assay. Basal total white blood cell and granulocyte counts did not appreciably
      differ between PML/RARalpha transgenic and control mice. Cell sorter analysis of
      CD11b+ bone marrow cells revealed similar CD11b+ populations in transgenic and
      control mice. However, in vitro clonal growth assays performed on peripheral
      blood from transgenic versus control mice revealed a marked reduction of myeloid
      progenitors, especially in those responding to granulocyte/ macrophage colony
      stimulating factor. Granulocyte/macrophage colony-stimulating factor and kit
      ligand cotreatment did not overcome this inhibition. Impaired myelopoiesis in
      vivo was shown by stressing these mice with sublethal irradiation. Following
      irradiation, PML/RARalpha transgenic mice, as compared with controls, more
      rapidly depressed peripheral white blood cell and granulocyte counts. As
      expected, nearly all control mice (94.4%) survived irradiation, yet this
      irradiation was lethal to 45.8% of PML/RARalpha transgenic mice. Lethality was
      associated with more severe leukopenia in transgenic versus control mice.
      Retinoic acid treatment of irradiated PML/RARalpha mice enhanced granulocyte
      recovery. These data suggest that abnormal myelopoiesis due to PML/RARalpha
      expression is an early event in oncogenic transformation.

PMID- 8755575
TI  - Role of the p21 cyclin-dependent kinase inhibitor in limiting intimal cell
      proliferation in response to arterial injury.
AB  - Arterial injury induces a series of proliferative, vasoactive, and inflammatory
      responses that lead to vascular proliferative diseases, including atherosclerosis
      and restenosis. Although several factors have been defined which stimulate this
      process in vivo, the role of specific cellular gene products in limiting this
      response is not well understood. The p21 cyclin-dependent kinase inhibitor
      affects cell cycle progression, senescence, and differentiation in transformed
      cells, but its expression in injured blood vessels has not been investigated. In
      this study, we report that p21 protein is induced in porcine arteries following
      balloon catheter injury and suggest that p21 is likely to play a role in limiting
      arterial cell proliferation in vivo. Vascular endothelial and smooth muscle cell
      growth was arrested through the ability of p21 to inhibit progression through the
      G1 phase of the cell cycle. Following injury to porcine arteries, p21 gene
      product was detected in the neointima and correlated inversely with the location
      and kinetics of intimal cell proliferation. Direct gene transfer of p21 using an
      adenoviral vector into balloon injured porcine arteries inhibited the development
      of intimal hyperplasia. Taken together, these findings suggest that p21, and
      possibly related cyclin-dependent kinase inhibitors, may normally regulate
      cellular proliferation following arterial injury, and strategies to increase its
      expression may prove therapeutically beneficial in vascular diseases.

PMID- 8755576
TI  - Induction of intestinal epithelial proliferation by glucagon-like peptide 2.
AB  - Injury, inflammation, or resection of the small intestine results in severe
      compromise of intestinal function. Nevertheless, therapeutic strategies for
      enhancing growth and repair of the intestinal mucosal epithelium are currently
      not available. We demonstrate that nude mice bearing subcutaneous proglucagon
      producing tumors exhibit marked proliferation of the small intestinal epithelium.
      The factor responsible for inducing intestinal proliferation was identified as
      glucagon-like peptide 2 (GLP-2), a 33-aa peptide with no previously ascribed
      biological function. GLP-2 stimulated crypt cell proliferation and consistently
      induced a marked increase in bowel weight and villus growth of the jejunum and
      ileum that was evident within 4 days after initiation of GLP-2 administration.
      These observations define a novel biological role for GLP-2 as an intestinal
      derived peptide stimulator of small bowel epithelial proliferation.

PMID- 8755577
TI  - Correction in trans for Fabry disease: expression, secretion and uptake of alpha
      galactosidase A in patient-derived cells driven by a high-titer recombinant
      retroviral vector.
AB  - Fabry disease is an X-linked metabolic disorder due to a deficiency of alpha
      galactosidase A (alpha-gal A; EC 3.2.1.22). Patients accumulate
      glycosphingolipids with terminal alpha-galactosyl residues that come from
      intracellular synthesis, circulating metabolites, or from the biodegradation Of
      senescent cells. Patients eventually succumb to renal, cardio-, or
      cerebrovascular disease. No specific therapy exists. One possible approach to
      ameliorating this disorder is to target corrective gene transfer therapy to
      circulating hematopoietic cells. Toward this end, an amphotropic virus-producer
      cell line has been developed that produces a high titer (>10(6) i.p. per ml)
      recombinant retrovirus constructed to transduce and correct target cells. Virus
      producer cells also demonstrate expression of large amounts of both intracellular
      and secreted alpha-gal A. To examine the utility of this therapeutic vector, skin
      fibroblasts from Fabry patients were corrected for the metabolic defect by
      infection with this recombinant virus and secreted enzyme was observed.
      Furthermore, the secreted enzyme was found to be taken up by uncorrected cells in
      a mannose-6-phosphate receptor-dependent manner. In related experiments,
      immortalized B cell lines from Fabry patients, created as a hematologic delivery
      test system, were transduced. As with the fibroblasts, transduced patient B cell
      lines demonstrated both endogenous enzyme correction and a small amount of
      secretion together with uptake by uncorrected cells. These studies demonstrate
      that endogenous metabolic correction in transduced cells, combined with
      secretion, may provide a continuous source of corrective material in trans to
      unmodified patient bystander cells (metabolic cooperativity).

PMID- 8755578
TI  - Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase
      deficient mice.
AB  - gamma-Glutamyl transpeptidase (GGT) is an ectoenzyme that catalyzes the first
      step in the cleavage of glutathione (GSH) and plays an essential role in the
      metabolism of GSH and GSH conjugates of carcinogens, toxins, and eicosanoids. To
      learn more about the role of GGT in metabolism in vivo, we used embryonic stem
      cell technology to generate GGT-deficient (GGTm1/GGTm1) mice. GGT-deficient mice
      appear normal at birth but grow slowly and by 6 weeks are about half the weight
      of wild-type mice. They are sexually immature, develop cataracts, and have coats
      with a gray cast. Most die between 10 and 18 weeks. Plasma and urine GSH levels
      in the GGTm1/GGTm1 mice are elevated 6-fold and 2500-fold, respectively, compared
      with wild-type mice. Tissue GSH levels are markedly reduced in eye, liver, and
      pancreas. Plasma cyst(e)ine levels in GGTm1/GGTm1 mice are reduced to
      approximately 20% of wild-type mice. Oral administration of N-acetylcysteine to
      GGTm1/GGTm1 mice results in normal growth rates and partially restores the normal
      agouti coat color. These findings demonstrate the importance of GGT and the gamma
      glutamyl cycle in cysteine and GSH homeostasis.

PMID- 8755579
TI  - Diazepam binding inhibitor is a potent cholecystokinin-releasing peptide in the
      intestine.
AB  - Pancreatic proteases in the duodenum inhibit the release of cholecystokinin (CCK)
      and thus exert feedback control of pancreatic exocrine secretion. Exclusion of
      proteases from the duodenum either by the diversion of bile-pancreatic juice or
      by the addition of protease inhibitors stimulates exocrine pancreatic secretion.
      The mechanism by which pancreatic proteases in the duodenum regulate CCK
      secretion is unknown. In this study, we isolated a trypsin-sensitive peptide that
      is secreted intraduodenally, releases CCK, and stimulates pancreatic enzyme
      secretion in rats. This peptide was found to be identical to the porcine diazepam
      binding inhibitor by peptide sequencing and mass spectrometry analysis.
      Intraduodenal infusion of 200 ng of synthetic porcine diazepam binding inhibitor1
      86 in rats significantly stimulated pancreatic amylase output. Infusion of the
      CCK antagonist MK-329 completely blocked the diazepam binding inhibitor
      stimulated amylase secretion. Similarly, diazepam binding inhibitor33-52
      [corrected] also stimulated CCK release and pancreatic secretion in a dose
      dependent manner although it was 100 times less potent than the whole peptide.
      Using a perfusion system containing isolated mucosal cells from the proximal
      intestine of rats, porcine diazepam binding inhibitor 10(-12) M) dose dependently
      stimulated CCK secretion. In separate studies, it was demonstrated that luminal
      secretion of the diazepam binding inhibitor immunoreactivity (7.5 X 10(11) M)
      could be detected in rat's intestinal washing following the diversion of bile
      pancreatic juice. The secretion of this peptide was inhibited by atropine. In
      conclusion, we have isolated and characterized a CCK-releasing peptide that has a
      sequence identical to the porcine diazepam binding inhibitor from pig intestinal
      mucosa and that stimulates CCK release when administered intraduodenally in rat.
      This peptide may mediate feedback regulation of pancreatic enzyme secretion.

PMID- 8755580
TI  - A potential pathogenetic mechanism for multiple endocrine neoplasia type 2
      syndromes involves ret-induced impairment of terminal differentiation of
      neuroepithelial cells.
AB  - Germ-line missense mutations of the receptor-like tyrosine kinase ret are the
      causative genetic event of the multiple endocrine neoplasia (MEN) type 2A and
      type 2B syndromes and of the familial medullary thyroid carcinoma. We have used
      the rat pheochromocytoma cell line, PC12, as a model system to investigate the
      mechanism or mechanisms by which expression of activated ret alleles contributes
      to the neoplastic phenotype in neuroendocrine cells. Here we show that stable
      expression of ret mutants (MEN2A and MEN2B alleles) in PC12 cells causes a
      dramatic conversion from a round to a flat morphology, accompanied by the
      induction of genes belonging to the early as well as the delayed response to
      nerve growth factor. However, in the transfected PC12 cells, the continuous
      expression of neuronal specific genes is not associated with the suppression of
      cell proliferation. Furthermore, expression of ret mutants renders PC12 cells
      unresponsive to nerve growth factor-induced inhibition of proliferation. These
      results suggest that induction of an aberrant pattern of differentiation,
      accompanied by unresponsiveness to growth-inhibitory physiological signals, may
      be part of the mechanism of action of activated ret alleles in the pathogenesis
      of neuroendocrine tumors associated with MEN2 syndromes.

PMID- 8755581
TI  - A knock-out model of paroxysmal nocturnal hemoglobinuria: Pig-a(-) hematopoiesis
      is reconstituted following intercellular transfer of GPI-anchored proteins.
AB  - We created a "knockout" embryonic stem cell via targeted disruption of the
      phosphatidylinositol glycan class A (Pig-a) gene, resulting in loss of expression
      of cell surface glycosyl phosphatidylinositol-anchored proteins and reproducing
      the mutant phenotype of the human disease paroxysmal nocturnal hemoglobinuria.
      Morphogenesis of Pig-a- embryoid bodies (EB) in vitro was grossly aberrant and,
      unlike EB derived from normal embryonic stem cells, Pig-A EB produced no
      secondary hematopoietic colonies. Chimeric EB composed of control plus Pig-A-
      cells, however, appeared normal, and hematopoiesis from knock-out cells was
      reconstituted. Transfer in situ of glycosyl phosphatidylinositol-anchored
      proteins from normal to knock-out cells was demonstrated by two-color fluorescent
      analysis, suggesting a possible mechanism for these functional effects.
      Hematopoietic cells with mutated PIG-A genes in humans with paroxysmal nocturnal
      hemoglobinuria may be subject to comparable pathophysiologic processes and
      amenable to similar therapeutic protein transfer.

PMID- 8755582
TI  - Induction of mucosal immune responses against a heterologous antigen fused to
      filamentous hemagglutinin after intranasal immunization with recombinant
      Bordetella pertussis.
AB  - Live vaccine vectors are usually very effective and generally elicit immune
      responses of higher magnitude and longer duration than nonliving vectors.
      Consequently, much attention has been turned to the engineering of oral pathogens
      for the delivery of foreign antigens to the gut-associated lymphoid tissues.
      However, no bacterial vector has yet been designed to specifically take advantage
      of the nasal route of mucosal vaccination. Herein we describe a genetic system
      for the expression of heterologous antigens fused to the filamentous
      hemagglutinin (FHA) in Bordetella pertussis. The Schistosoma mansoni glutathione
      S-transferase (Sm28GST) fused to FHA was detected at the cell surface and in the
      culture supernatants of recombinant B. pertussis. The mouse colonization capacity
      and autoagglutination of the recombinant microorganism were indistinguishable
      from those of the wild-type strain. In addition, and in contrast to the wild-type
      strain, a single intranasal administration of the recombinant strain induced both
      IgA and IgG antibodies against Sm28GST and against FHA in the bronchoalveolar
      lavage fluids. No anti-Sm28GST antibodies were detected in the serum, strongly
      suggesting that the observed immune response was of mucosal origin. This
      demonstrates, to our knowledge, for the first time that recombinant respiratory
      pathogens can induce mucosal immune responses against heterologous antigens, and
      this may constitute a first step toward the development of combined live vaccines
      administrable via the respiratory route.

PMID- 8755583
TI  - Apoptosis and APC in colorectal tumorigenesis.
AB  - Tumors result from disruptions in the homeostatic mechanisms that regulate cell
      birth and cell death. In colon cancer, one of the earliest manifestation of this
      imbalance is the formation of polyps, caused by somatic and inherited mutations
      of the adenomatous polyposis coli (APC) tumor suppressor gene in both humans and
      mice. While the importance of APC in tumorigenesis is well documented, how it
      functions to prevent tumors remains a mystery. Using a novel inducible expression
      system, we show that expression of APC in human colorectal cancer cells
      containing endogenous inactive APC alleles results in a substantial diminution of
      cell growth. Further evaluation demonstrated that this was due to the induction
      of cell death through apoptosis. These results suggest that apoptosis plays a
      role not only in advanced tumors but also at the very earliest stages of
      neoplasia.

PMID- 8755584
TI  - Conditional reduction of human immunodeficiency virus type 1 replication by a
      gain-of-herpes simplex virus 1 thymidine kinase function.
AB  - The development of an effective vaccine for human immunodeficiency virus type 1
      (HIV-1) would be a major advance toward controlling the AIDS pandemic. Several
      disparate strategies for a safe and effective HIV vaccine have been proposed.
      Recent data suggest that loss-of-function live-attenuated virus could be a safe
      lentivirus vaccine. Here, we propose a gain-of-function approach that can
      complement loss-of-function in enhancing the safety profile of a live-attenuated
      virus. We describe an example in which ganciclovir (GCV) was used to treat
      effectively nef(-)HIV-1 engineered to express herpes simplex virus (HSV-1)
      thymidine kinase (TK). This treatment was found to be highly efficient in
      controlling HIV-1 spread in tissue culture and in a small animal (hu-PBL-SCID)
      model. We demonstrate that one distinct advantage of GCV-HSV-TK treatment is the
      elimination of integrated proviruses, a goal not easily achieved with other
      antiretrovirals.

PMID- 8755585
TI  - Signature p53 mutation at DNA cross-linking sites in 8-methoxypsoralen and
      ultraviolet A (PUVA)-induced murine skin cancers.
AB  - A combination of psoralen and ultraviolet A radiation (PUVA) is widely used in
      the treatment of psoriasis. However, PUVA treatment increases the risk of
      developing skin cancer in psoriasis patients and induces skin cancer in mice.
      Since the DNA damage induced by PUVA is quite different from that induced by UV,
      we investigated whether PUVA-induced mouse skin cancers display carcinogen
      specific mutations in the p53 tumor suppressor gene. The results indicated that
      10 of 13 (77%) PUVA-induced skin tumors contained missense mutations
      predominantly at exons 6 and 7. In contrast, tumor-adjacent, PUVA-exposed skin
      from tumor-bearing animals did not exhibit p53 mutation in exons 4-8.
      Interestingly, about 40% of all mutations in PUVA-induced skin tumors occurred at
      5'-TA sites, and an equal number of mutations occurred at one base flanking 5'TA
      or 5'-TAT sites. Since PUVA induces DNA cross-links exclusively at these sites
      and since UV "signature" mutations were rarely detected in PUVA-induced skin
      cancers, we can conclude that PUVA acts as a carcinogen by inducing unique PUVA
      signature mutations in p53. This finding may have implications for identifying
      the etiology of skin cancer in psoriasis patients who have undergone PUVA
      therapy.

PMID- 8755586
TI  - The recombination signals for adeno-associated virus site-specific integration.
AB  - The adeno-associated virus (AAV) genome integrates site specifically into a
      defined region of human chromosome 19 (termed AAVS1). Using a functional assay
      for AAV integration into AAVS1 DNA propagated as an episome, we obtained evidence
      that a 33-nucleotide AAVS1 DNA sequence contains the minimum signal required for
      targeted integration. The recombination signal comprises a DNA-binding motif for
      the AAV regulatory Rep protein [Rep binding site (RBS)] separated by an eight
      nucleotide spacer from a sequence that can act as a substrate for Rep
      endonucleolytic activity [terminal resolution site (TRS)]. Mutations in either
      the AAVS1-encoded RBS or TRS elements abort targeted integration. Since both the
      RBS and TRS elements are present in the viral origin of replication and are
      required for AAV replication, targeted integration into chromosome 19 AAVS1 DNA
      may involve a replicative type of recombination that is discussed. An additional
      chromosome 19 element, which is responsible for DNA rearrangements in episomes
      propagating AAVS1 DNA, was identified and shown not to be required for AAV
      episomal integration, despite its location adjacent to the recombination signal.

PMID- 8755587
TI  - Limited surface exposure of Borrelia burgdorferi outer surface lipoproteins.
AB  - We used novel immunofluorescence strategies to demonstrate that outer surface
      proteins (Osps) A, B and C of Borrelia burgdorferi have limited surface exposure,
      finding that contradicts the prevailing viewpoint that these antigens are
      exclusively surface exposed. Light labeling was observed when antibodies to OspA
      or OspB were added to motile organisms, whereas intense fluorescence was observed
      when the same slides were methanol-fixed and reprobed. Modest labeling also was
      observed when spirochetes encapsulated in agarose beads (gel microdroplets) were
      incubated with antibodies to these same two antigens. This contrasted with the
      intense fluorescence observed when encapsulated spirochetes were probed in the
      presence of 0.06% Triton X-100, which selectively removed outer membranes.
      Proteinase K (PK) treatment of encapsulated spirochetes abrogated surface
      labeling. However, PK-treated spirochetes fluoresced intensely after incubation
      with antibodies to OspA or OspB in the presence of detergent, confirming the
      existence of large amounts of subsurface Osp antigens. Modest surface labeling
      once again was detected when PK-treated spirochetes were reprobed after overnight
      incubation, a result consistent with the existence of a postulated secretory
      apparatus that shuttles lipoproteins to the borrelial surface. Last, experiments
      with the OspC-expressing B. burgdorferi strain 297 revealed that this antigen was
      barely detectable on spirochetal surfaces even though it was a major constituent
      of isolated outer mem- branes. We propose a model of B. burgdorferi molecular
      architecture that helps to explain spirochetal persistence during chronic Lyme
      disease.

PMID- 8755588
TI  - 16S rRNA genes reveal stratified open ocean bacterioplankton populations related
      to the Green Non-Sulfur bacteria.
AB  - Microorganisms play an important role in the biogeochemistry of the ocean surface
      layer, but spatial and temporal structures in the distributions of specific
      bacterioplankton species are largely unexplored, with the exceptions of those
      organisms that can be detected by either autofluorescence or culture methods. The
      use of rRNA genes as genetic markers provides a tool by which patterns in the
      growth, distribution, and activity of abundant bacterioplankton species can be
      studied regardless of the ease with which they can be cultured. Here we report an
      unusual cluster of related 16S rRNA genes (SAR202, SAR263, SAR279, SAR287,
      SAR293, SAR307) cloned from seawater collected at 250 m in the Sargasso Sea in
      August 1991, when the water column was highly stratified and the deep chlorophyll
      maximum was located at a depth of 120 m. Phylogenetic analysis and an unusual 15
      bp deletion confirmed that the genes were related to the Green Non-Sulfur phylum
      of the domain Bacteria. This is the first evidence that representatives of this
      phylum occur in the open ocean. Oligonucleotide probes were used to examine the
      distribution of the SAR202 gene cluster in vertical profiles (0-250 m) from the
      Atlantic and Pacific Oceans, and in discrete (monthly) time series (O and 200 m)
      (over 30 consecutive months in the Western Sargasso Sea. The data provide robust
      statistical support for the conclusion that the SAR202 gene cluster is
      proportionately most abundant at the lower boundary of the deep chlorophyll
      maximum (P = 2.33 x 10(-5)). These results suggest that previously unsuspected
      stratification of microbial populations may be a significant factor in the
      ecology of the ocean surface layer.

PMID- 8755589
TI  - Peptide methionine sulfoxide reductase contributes to the maintenance of adhesins
      in three major pathogens.
AB  - Pathogenic bacteria rely on adhesins to bind to host tissues. Therefore, the
      maintenance of the functional properties of these extracellular macromolecules is
      essential for the pathogenicity of these microorganisms. We report that peptide
      methionine sulfoxide reductase (MsrA), a repair enzyme, contributes to the
      maintenance of adhesins in Streptococcus pneumoniae, Neisseria gonorrhoeae, and
      Escherichia coli. A screen of a library of pneumococcal mutants for loss of
      adherence uncovered a MsrA mutant with 75% reduced binding to GalNAcbeta1-4Gal
      containing eukaryotic cell receptors that are present on type II lung cells and
      vascular endothelial cells. Subsequently, it was shown that an E. coli msrA
      mutant displayed decreased type I fimbriae-mediated, mannose-dependent,
      agglutination of erythrocytes. Previous work [Taha, M. K., So, M., Seifert, H.
      S., Billyard, E. & Marchal, C. (1988) EMBO J. 7, 4367-4378] has shown that
      mutants with defects in the pilA-pilB locus from N. gonorrhoeae were altered in
      their production of type IV pili. We show that pneumococcal MsrA and gonococcal
      PilB expressed in E. coli have MsrA activity. Together these data suggest that
      MsrA is required for the proper expression or maintenance of functional adhesins
      on the surfaces of these three major pathogenic bacteria.

PMID- 8755590
TI  - Differential expression of the ToxR regulon in classical and E1 Tor biotypes of
      Vibrio cholerae is due to biotype-specific control over toxT expression.
AB  - The two major disease-causing biotypes of Vibrio cholerae, classical and El Tor,
      exhibit differences in their epidemic nature. Their behavior in the laboratory
      also differs in that El Tor strains produce two major virulence factors, cholera
      toxin (CT) and the toxin coregulated pilus (TCP), only under very restricted
      growth conditions, whereas classical strains do so in standard laboratory medium.
      Expression of toxin and TCP is controlled by two activator proteins, ToxR and
      ToxT, that operate in cascade fashion with ToxR controlling the synthesis of
      ToxT. Both biotypes express equivalent levels of ToxR, but only classical strains
      appear to express ToxT when grown in standard medium. In this report we show that
      restrictive expression of CT and TCP can be overcome in El Tor strains by
      expressing ToxT independently of ToxR. An El Tor strain lacking functional ToxT
      does not express CT or TCP, ruling out existence of a cryptic pathway for
      virulence regulation in this biotype. These results may have implications for
      understanding the evolution of El Tor strains toward reduced virulence with
      respect to classical strains.

PMID- 8755591
TI  - Extensive alteration of fungal gene transcript accumulation and elevation of G
      protein-regulated cAMP levels by a virulence-attenuating hypovirus.
AB  - Persistent infection of the chestnut blight fungus Cryphonectria parasitica with
      the prototypic hypovirus CHVI-713 results in attenuation of fungal virulence
      (hypo-virulence) and reduced accumulation of the GTP-binding (G) protein a
      subunit CPG-1. Transgenic cosuppression of CPG-1 accumulation in the absence of
      virus infection also confers hypovirulence. We now report the use of mRNA
      differential display to examine the extent to which virus infection alters fungal
      gene transcript accumulation and to assess the degree to which modification of
      CPG-1 signal transduction contributes to this alteration. More than 400 PCR
      products were identified that either increased (296 products) or decreased (127
      products) in abundance as a result of virus infection. Significantly, 65% of
      these products exhibited similar changes as a result of CPG-1 cosuppression in
      the absence of virus infection. We also report that both virus infection and CPG
      1 cosuppression elevate cAMP levels 3- to 5-fold. Additionally, it was possible
      to mimic the effect of virus infection and CPG-1 cosuppression on transcript
      accumulation for representative fungal genes by drug-induced elevation of cAMP
      levels. These results strengthen and extend previous indications that hypovirus
      infection causes a significant and persistent alteration of fungal gene
      expression/transcript accumulation. They further show that this alteration is
      primarily mediated through modification of the CPG-1 signaling pathway and
      suggest that, similar to mammalian Gi alpha subunits, CPG-1 functions as a
      negative modulator of adenylyl cyclase. Finally, these results suggest a role for
      G-protein-regulated cAMP accumulation in hypovirus-mediated alteration of fungal
      gene expression.

PMID- 8755592
TI  - The extraordinarily rapid disappearance of entoptic images.
AB  - It has been known for more than 40 years that images fade from perception when
      they are kept at the same position on the retina by abrogating eye movements.
      Although aspects of this phenomenon were described earlier, the use of close
      fitting contact lenses in the 1950s made possible a series of detailed
      observations on eye movements and visual continuity. In the intervening decades,
      many investigators have studied the role of image motion on visual perception.
      Although several controversies remain, it is clear that images deteriorate and in
      some cases disappear following stabilization; eye movements are, therefore,
      essential to sustained exoptic vision. The time course of image degradation has
      generally been reported to be a few seconds to a minute or more, depending upon
      the conditions. Here we show that images of entoptic vascular shadows can
      disappear in less than 80 msec. The rapid vanishing of these images implies an
      active mechanism of image erasure and creation as the basis of normal visual
      processing.

PMID- 8755593
TI  - GABAergic feedforward projections from the inferior colliculus to the medial
      geniculate body.
AB  - A novel and robust projection from gamma-aminobutyric acid-containing (GABAergic)
      inferior colliculus neurons to the media] geniculate body (MGB) was discovered in
      the cat using axoplasmic transport methods combined with immunocytochemistry.
      This input travels with the classical inferior colliculus projection to the MGB,
      and it is a direct ascending GABAergic pathway to the sensory thalamus that may
      be inhibitory. This bilateral projection constitutes 10-30% of the neurons in the
      auditory tectothalamic system. Studies by others have shown that comparable input
      to the corresponding thalamic visual or somesthetic nuclei is absent. This
      suggests that monosynaptic inhibition or disinhibition is a prominent feature in
      the MGB and that differences in neural circuitry distinguish it from its thalamic
      visual and somesthetic counterparts.

PMID- 8755594
TI  - Long-term modifications of synaptic efficacy in the human inferior and middle
      temporal cortex.
AB  - The primate temporal cortex has been demonstrated to play an important role in
      visual memory and pattern recognition. It is of particular interest to
      investigate whether activity-dependent modification of synaptic efficacy, a
      presumptive mechanism for learning and memory, is present in this cortical
      region. Here we address this issue by examining the induction of synaptic
      plasticity in surgically resected human inferior and middle temporal cortex. The
      results show that synaptic strength in the human temporal cortex could undergo
      bidirectional modifications, depending on the pattern of conditioning
      stimulation. High frequency stimulation (100 or 40 Hz) in layer IV induced long
      term potentiation (LTP) of both intracellular excitatory postsynaptic potentials
      and evoked field potentials in layers II/III. The LTP induced by 100 Hz tetanus
      was blocked by 50-100 microM DL-2-amino-5-phosphonovaleric acid, suggesting that
      N-methyl-D-aspartate receptors were responsible for its induction. Long-term
      depression (LTD) was elicited by prolonged low frequency stimulation (1 Hz, 15
      min). It was reduced, but not completely blocked, by DL-2-amino-5
      phosphonovaleric acid, implying that some other mechanisms in addition to N
      methyl-DL-aspartate receptors were involved in LTD induction. LTD was input
      specific, i.e., low frequency stimulation of one pathway produced LTD of synaptic
      transmission in that pathway only. Finally, the LTP and LTD could reverse each
      other, suggesting that they can act cooperatively to modify the functional state
      of cortical network. These results suggest that LTP and LTD are possible
      mechanisms for the visual memory and pattern recognition functions performed in
      the human temporal cortex.

PMID- 8755596
TI  - Discrimination among pheromone component blends by interneurons in male antennal
      lobes of two populations of the turnip moth, Agrotis segetum.
AB  - A difference in female pheromone production and male behavioral response has
      previously been found in two populations of the turnip moth, Agrotis segetum,
      originating from Sweden and Zimbabwe, respectively. In this study, we
      investigated the pheromone response of antennal lobe interneurons of males of the
      two populations by intracellular recordings, stimulating with single pheromone
      components and various inter- and intra-populational pheromone blends. Three
      major physiological types of antennal lobe neurons were established in the two
      populations according to their responses to different stimuli. One type responded
      broadly to almost all the stimuli tested. The second type responded selectively
      to some of the single components and blends. The third type did not respond to
      any single components but did respond to certain blends. Furthermore, some
      neurons of the second and third type recognized strain specific differences in
      ratios between pheromone components. Both projection neurons and local
      interneurons were found among these three types. Two pheromone responding
      bilateral projection neurons are reported for the first time in this paper.

PMID- 8755595
TI  - Amygdala activity at encoding correlated with long-term, free recall of emotional
      information.
AB  - Positron emission tomography of cerebral glucose metabolism in adult human
      subjects was used to investigate amygdaloid complex (AC) activity associated with
      the storage of long-term memory for emotionally arousing events. Subjects viewed
      two videos (one in each of two separate positron emission tomography sessions,
      separated by 3-7 days) consisting either of 12 emotionally arousing film clips
      ("E" film session) or of 12 relatively emotionally neutral film clips ("N" film
      session), and rated their emotional reaction to each film clip immediately after
      viewing it. Three weeks after the second session, memory for the videos was
      assessed in a free recall test. As expected, the subjects' average emotional
      reaction to the E films was higher than that for the N films. In addition, the
      subjects recalled significantly more E films than N films. Glucose metabolic rate
      of the right AC while viewing the E films was highly correlated with the number
      of E films recalled. AC activity was not significantly correlated with the number
      of N films recalled. The findings support the view derived from both animal and
      human investigations that the AC is selectively involved with the formation of
      enhanced long-term memory associated with emotionally arousing events.

PMID- 8755597
TI  - Deficits in memory and hippocampal long-term potentiation in mice with reduced
      calbindin D28K expression.
AB  - The influx of calcium into the postsynaptic neuron is likely to be an important
      event in memory formation. Among the mechanisms that nerve cells may use to alter
      the time course or size of a spike of intracellular calcium are cytosolic calcium
      binding or "buffering" proteins. To consider the role in memory formation of one
      of these proteins, calbindin D28K, which is abundant in many neurons, including
      the CA1 pyramidal cells of the hippocampus, transgenic mice deficient in
      calbindin D28K have been created. These mice show selective impairments in
      spatial learning paradigms and fail to maintain long-term potentiation. These
      results suggest a role for calbindin D28K protein in temporally extending a
      neuronal calcium signal, allowing the activation of calcium-dependent
      intracellular signaling pathways underlying memory function.

PMID- 8755598
TI  - Dopamine inhibits mammalian photoreceptor Na+,K+-ATPase activity via a selective
      effect on the alpha3 isozyme.
AB  - The rat retina contains dopaminergic interplexiform cells that send processes to
      the outer plexiform layer where dopamine is released in a light-dependent manner.
      We report herein that physiologically relevant concentrations of dopamine
      inhibited ouabain-sensitive photoreceptor oxygen consumption in dark- and light
      adapted rat retinas and inhibited Na+,K+-ATPase specific activity (EC 3.6.1.37)
      in a rat rod outer-inner segment preparation. Experiments with the selective D1
      agonist fenoldopam or D2 agonist quinpirole and experiments with dopamine plus
      either the D1 antagonist SCH23390 or D2/D4 antagonist clozapine showed that the
      inhibition of oxygen consumption and enzyme activity were mediated by D2/D4-like
      receptors. The amphetamine-induced release of dopamine, monitored by the
      inhibition of oxygen consumption, was blocked by L-2-amino-4-phosphonobutyric
      acid and kynurenic acid. Pharmacological and biochemical experiments determined
      that the IC50 values of ouabain for the alpha1-low and alpha3-high ouabain
      affinity isozymes of photoreceptor Na+,K+-ATPase were approximately 10(-5) and
      approximately 10(-7) M, respectively, and that the D2/D4-like mediated inhibition
      of Na+,K+-ATPase was exclusively selective for the alpha3 isozyme. The dopamine
      mediated inhibition of alpha3 first occurred at 5 nM, was maximal at 100 microM (
      47%), had an IC50 value of 382 +/- 23 nM, and exhibited negative cooperativity
      (Hill coefficient, 0.27). Prior homogenization of the rod outer-inner segment
      completely prevented the long-lasting inhibition, suggesting that the effect was
      coupled to a second messenger. Although the physiological significance of our
      findings to photoreceptor function is unknown, we hypothesize that these results
      may have relevance for the temporal tuning properties of rods.

PMID- 8755599
TI  - Induction of long-term potentiation is associated with major ultrastructural
      changes of activated synapses.
AB  - Long-term potentiation (LTP), an increase in synaptic efficacy believed to
      underlie learning and memory mechanisms, has been proposed to involve structural
      modifications of synapses. Precise identification of the morphological changes
      associated with LTP has however been hindered by the difficulty in distinguishing
      potentiated or activated from nonstimulated synapses. Here we used a cytochemical
      method that allowed detection in CA1 hippocampus at the electron microscopy level
      of a stimulation-specific, D-AP5-sensitive accumulation of calcium in
      postsynaptic spines and presynaptic terminals following application of high
      frequency trains. Morphometric analyses carried out 30-40 min after LTP induction
      revealed dramatic ultrastructural differences between labeled and nonlabeled
      synapses. The majority of labeled synapses (60%) exhibited perforated
      postsynaptic densities, whereas this proportion was only 20% in nonlabeled
      synaptic contacts. Labeled synaptic profiles were also characterized by a larger
      apposition zone between pre- and postsynaptic structures, longer postsynaptic
      densities, and enlarged spine profiles. These results add strong support to the
      idea that ultrastructural modifications and specifically an increase in
      perforated synapses are associated with LTP induction in field CA1 of hippocampus
      and they suggest that a majority of activated contacts may exhibit such changes.

PMID- 8755600
TI  - Cholinergic agonists stimulate secretion of soluble full-length amyloid precursor
      protein in neuroendocrine cells.
AB  - The Abeta peptide of Alzheimer disease is derived from the proteolytic processing
      of the amyloid precursor proteins (APP), which are considered type I
      transmembrane glycoproteins. Recently, however, soluble forms of full-length APP
      were also detected in several systems including chromaffin granules. In this
      report we used antisera specific for the cytoplasmic sequence of APP to show that
      primary bovine chromaffin cells secrete a soluble APP, termed solAPPcyt, of an
      apparent molecular mass of 130 kDa. This APP was oversecreted from Chinese
      hamster ovary cells transfected with a full-length APP cDNA indicating that
      solAPPcyt contained both the transmembrane and Abeta sequence. Deglycosylation of
      solAPPcyt showed that it contained both N- and O-linked sugars, suggesting that
      this APP was transported through the endoplasmic reticulum-Golgi pathway.
      Secretion of solAPPcyt from primary chromatin cells was temperature-, time-, and
      energy-dependent and was stimulated by cell depolarization in a Ca2+-dependent
      manner. Cholinergic receptor agonists, including acetylcholine, nicotine, or
      carbachol, stimulated the rapid secretion of solAPPcyt, a process that was
      inhibited by cholinergic antagonists. Stimulation of solAPPcyt secretion was
      paralleled by a stimulation of secretion in catecholamines and chromogranin A,
      indicating that secretion of solAPPcyt was mediated by chromaffin granule
      vesicles. Taken together, our results show that release of the potentially
      amyloidogenic solAPPcyt is an active cellular process mediated by both the
      constitutive and regulated pathways. solAPPcyt was also detected in human
      cerebrospinal fluid. Combined with the neuronal physiology of chromaffin cells,
      our data suggest that cholinergic agonists may stimulate the release of this APP
      in neuronal synapses where it may exert its biological functions. Moreover,
      vesicular or secreted solAPPcyt may serve as a soluble precursor of Abeta.

PMID- 8755601
TI  - kappa opioid receptors in human microglia downregulate human immunodeficiency
      virus 1 expression.
AB  - Microglial cells, the resident macrophages of the brain, play an important role
      in the neuropathogenesis of human immunodeficiency virus type 1 (HIV-1), and
      recent studies suggest that opioid peptides regulate the function of macrophages
      from somatic tissues. We report herein the presence of kappa opioid receptors
      (KORs) in human fetal microglia and inhibition of HIV-1 expression in acutely
      infected microglial cell cultures treated with KOR ligands. Using reverse
      transcriptase-polymerase chain reaction and sequencing analyses, we found that
      mRNA for the KOR was constitutively expressed in microglia and determined that
      the nucleotide sequence of the open reading frame was identical to that of the
      human brain KOR gene. The expression of KOR in microglial cells was confirmed by
      membrane binding of [3H]U69,593, a kappa-selective ligand, and by indirect
      immunofluorescence. Treatment of microglial cell cultures with U50,488 or U69,593
      resulted in a dose-dependent inhibition of expression of the monocytotropic HIV-1
      SF162 strain. This antiviral effect of the kappa ligands was blocked by the
      specific KOR antagonist, nor-binaltrophimine. These findings suggest that kappa
      opioid agonists have immunomodulatory activity in the brain, and that these
      compounds could have potential in the treatment of HIV-1-associated
      encephalopathy.

PMID- 8755602
TI  - Starburst amacrine cells change from spiking to nonspiking neurons during retinal
      development.
AB  - The membrane excitability of cholinergic (starburst) amacrine cells was studied
      in the rabbit retina during postnatal development. Whole-cell patch-clamp
      recordings were made from 110 displaced starburst cells in a thin retina] slice
      preparation of rabbits between postnatal days P1 and P56 old. We report that
      displaced starburst cells undergo a dramatic transition from spiking to
      nonspiking, caused by a loss of voltage-gated Na currents. This change in
      membrane excitability occurred just after eye opening (P10), such that all of the
      starburst cells tested before eye opening had conspicuous tetrodotoxin-sensitive
      Na currents and action potentials, but none tested after the first 3 postnatal
      weeks had detectable Na currents or spikes. Our results suggest that starburst
      cells use action potentials transiently during development and probably play a
      functional role in visual development. These cells then cease to spike as the
      retina matures, presumably consistent with their role in visual processing in the
      mature retina.

PMID- 8755603
TI  - Differential distribution of two ATP-gated channels (P2X receptors) determined by
      immunocytochemistry.
AB  - Several P2X receptor subunits were recently cloned; of these, one was cloned from
      the rat vas deferens (P2X1) and another from pheochromocytoma (PC12) cells
      differentiated with nerve growth factor (P2X2). Peptides corresponding to the C
      terminal portions of the predicted receptor proteins (P2X1 391-399 and P2X2 460
      472) were used to generate antisera in rabbits. The specificities of antisera
      were determined by staining human embryonic kidney cells stably transfected with
      either P2X1 or P2X2 receptors and by absorption controls with the cognate
      peptides. In the vas deferens and the ileal submucosa, P2X1 immunoreactivity (ir)
      was restricted to smooth muscle, whereas P2X2-ir was restricted to neurons and
      their processes. Chromaffin cells of the adrenal medulla and PC12 cells contained
      both P2X1- and P2X2-ir. P2X1-ir was also found in smooth muscle cells of the
      bladder, cardiac myocytes, and nerve fibers and terminals in the superficial
      dorsal horn of the spinal cord. In contrast, P2X2-ir was observed in scattered
      cells of the anterior pituitary, neurons in the hypothalamic arcuate and
      paraventricular nuclei, and catecholaminergic neurons in the olfactory bulb, the
      substantia nigra, ventral tegmental area, and locus coeruleus. A plexus of nerve
      fibers and terminals in the nucleus of the solitary tract contained P2X2-ir. This
      staining disappeared after nodose ganglionectomy, consistent with a presynaptic
      function. The location of the P2X1 subunit in smooth muscle is consistent with
      its role as a postjunctional receptor in autonomic transmission, while in
      neurons, these receptors appear in both postsynaptic and presynaptic locations.

PMID- 8755604
TI  - Amyloid beta-protein reduces acetylcholine synthesis in a cell line derived from
      cholinergic neurons of the basal forebrain.
AB  - The characteristic features of a brain with Alzheimer disease (AD) include the
      presence of neuritic plaques composed of amyloid beta-protein (Abeta) and
      reductions in the levels of cholinergic markers. Neurotoxic responses to Abeta
      have been reported in vivo and in vitro, suggesting that the cholinergic deficit
      in AD brain may be secondary to the degeneration of cholinergic neurons caused by
      Abeta. However, it remains to be determined if Abeta contributes to the
      cholinergic deficit in AD brain by nontoxic effects. We examined the effects of
      synthetic Abeta peptides on the cholinergic properties of a mouse cell line,
      SN56, derived from basal forebrain cholinergic neurons. Abeta 1-42 and Abeta 1-28
      reduced the acetylcholine (AcCho) content of the cells in a concentration
      dependent fashion, whereas Abeta 1-16 was inactive. Maximal reductions of 43% and
      33% were observed after a 48-h treatment with 100 nM of Abeta 1-42 and 50 pM of
      Abeta 1-28, respectively. Neither Abeta 1-28 nor Abeta 1-42 at a concentration of
      100 nM and a treatment period of 2 weeks was toxic to the cells. Treatment of the
      cells with Abeta 25-28 (48 h; 100 nM) significantly decreased AcCho levels,
      suggesting that the sequence GSNK (aa 25-28) is responsible for the AcCho
      reducing effect of Abeta. The reductions in AcCho levels caused by Abeta 1-42 and
      Abeta 1-28 were accompanied by proportional decreases in choline
      acetyltransferase activity. In contrast, acetylcholinesterase activity was
      unaltered, indicating that Abeta specifically reduces the synthesis of AcCho in
      SN56 cells. The reductions in AcCho content caused by Abeta 1-42 could be
      prevented by a cotreatment with all-trans-retinoic acid (10 nM), a compound
      previously shown to increase choline acetyltransferase mRNA expression in SN56
      cells. These results demonstrate a nontoxic, suppressive effect of Abeta on AcCho
      synthesis, an action that may contribute to the cholinergic deficit in AD brain.

PMID- 8755605
TI  - Purification, molecular cloning, and expression of the mammalian sigma1-binding
      site.
AB  - Sigma-ligands comprise several chemically unrelated drugs such as haloperidol,
      pentazocine, and ditolylguanidine, which bind to a family of low molecular mass
      proteins in the endoplasmic reticulum. These so-called sigma-receptors are
      believed to mediate various pharmacological effects of sigma-ligands by as yet
      unknown mechanisms. Based on their opposite enantioselectivity for benzomorphans
      and different molecular masses, two subtypes are differentiated. We purified the
      sigma1-binding site as a single 30-kDa protein from guinea pig liver employing
      the benzomorphan(+)[3H]pentazocine and the arylazide (-)[3H]azidopamil as
      specific probes. The purified (+)[3H]pentazocine-binding protein retained its
      high affinity for haloperidol, pentazocine, and ditolylguanidine. Partial amino
      acid sequence obtained after trypsinolysis revealed no homology to known
      proteins. Radiation inactivation of the pentazocine-labeled sigma1-binding site
      yielded a molecular mass of 24 +/- 2 kDa. The corresponding cDNA was cloned using
      degenerate oligonucleotides and cDNA library screening. Its open reading frame
      encoded a 25.3-kDa protein with at least one putative transmembrane segment. The
      protein expressed in yeast cells transformed with the cDNA showed the
      pharmacological characteristics of the brain and liver sigma1-binding site. The
      deduced amino acid sequence was structurally unrelated to known mammalian
      proteins but it shared homology with fungal proteins involved in sterol
      synthesis. Northern blots showed high densities of the sigma1-binding site mRNA
      in sterol-producing tissues. This is also in agreement with the known ability of
      sigma1-binding sites to interact with steroids, such as progesterone.

PMID- 8755606
TI  - Brain lipids that induce sleep are novel modulators of 5-hydroxytrypamine
      receptors.
AB  - Amide derivatives of fatty acids were recently isolated from cerebrospinal fluid
      of sleep-deprived animals and found to induce sleep in rats. To determine which
      brain receptors might be sensitive to these novel neuromodulators, we tested them
      on a range of receptors expressed in Xenopus oocytes. cis-9,10-Octadecenamide
      (ODA) markedly potentiated the action of 5-hydroxytryptamine (5-HT) on 5-HT2A and
      5-HT2C receptors, but this action was not shared by related compounds such as
      oleic acid and trans-9,10-octacenamide. ODA was active at concentrations as low
      as 1 nM. The saturated analog, octadecanamide, inhibited rather than potentiated
      5-HT2C responses. ODA had either no effect or only weak effects on other
      receptors, including muscarinic cholinergic, metabotropic glutamate, GABA(A), N
      methyl-D-asparate, or alpha-amino-3-hydroxy-5-methyl-4-isoxozolepropionic acid
      receptors. Modulation of 5-HT2 receptors by ODA and related lipids may represent
      a novel mechanism for regulation of receptors that activate G proteins and
      thereby play a role in alertness, sleep, and mood as well as disturbances of
      these states.

PMID- 8755607
TI  - Sensitivity of a renal K+ channel (ROMK2) to the inhibitory sulfonylurea compound
      glibenclamide is enhanced by coexpression with the ATP-binding cassette
      transporter cystic fibrosis transmembrane regulator.
AB  - We demonstrate here that coexpression of ROMK2, an inwardly rectifying ATP
      sensitive renal K+ channel (IKATP) with cystic fibrosis transmembrane regulator
      (CFTR) significantly enhances the sensitivity of ROMK2 to the sulfonylurea
      compound glibenclamide. When expressed alone, ROMK2 is relatively insensitive to
      glibenclamide. The interaction between ROMK2, CFTR, and glibenclamide is
      modulated by altering the phosphorylation state of either ROMK2, CFTR, or an
      associated protein, as exogenous MgATP and the catalytic subunit of protein
      kinase A significantly attenuate the inhibitory effect of glibenclamide on ROMK2.
      Thus CFTR, which has been demonstrated to interact with both Na+ and Cl- channels
      in airway epithelium, modulates the function of renal ROMK2 K+ channels.

PMID- 8755608
TI  - Oxygen causes fetal pulmonary vasodilation through activation of a calcium
      dependent potassium channel.
AB  - At birth, pulmonary vasodilation occurs as air-breathing life begins. The
      mechanism of O2-induced pulmonary vasodilation is unknown. We proposed that O2
      causes fetal pulmonary vasodilation through activation of a calcium-dependent
      potassium channel (KCa) via a cyclic nucleotide-dependent kinase. We tested this
      hypothesis in hemodynamic studies in acutely prepared fetal lambs and in patch
      clamp studies on resistance fetal pulmonary artery smooth muscle cells. Fetal O2
      tension (PaO2) was increased by ventilating the ewe with 100% O2, causing fetal
      total pulmonary resistance to decrease from 1.18 +/- 0.14 to 0.41 +/- 0.03 mmHg
      per ml per min. Tetraethylammonium and iberiotoxin, preferential KCa-channel
      inhibitors, attenuated O2-induced fetal pulmonary vasodilation, while
      glibenclamide, an ATP-sensitive K+-channel antagonist, had no effect. Treatment
      with either a guanylate cyclase antagonist (LY83583) or cyclic nucleotide
      dependent kinase inhibitors (H-89 and KT 5823) significantly attenuated O2
      induced fetal pulmonary vasodilation. Under hypoxic conditions (PaO2 = 25 mmHg),
      whole-cell K+-channel currents (Ik) were small and were inhibited by 1 mM
      tetraethylammonium or 100 nM charybdotoxin (CTX; a specific KCa-channel blocker).
      Normoxia (PaO2 = 120 mmHg) increased Ik by more than 300%, and this was reversed
      by 100 nM CTX. Nitric oxide also increased Ik. Resting membrane potential was 
      37.2 +/- 1.9 mV and cells depolarized on exposure to CTX, while hyperpolarizing
      in normoxia. We conclude that O2 causes fetal pulmonary vasodilation by
      stimulating a cyclic nucleotide-dependent kinase, resulting in KCa-channel
      activation, membrane hyperpolarization, and vasodilation.

PMID- 8755609
TI  - The whistle and the rattle: the design of sound producing muscles.
AB  - Vertebrate sound producing muscles often operate at frequencies exceeding 100 Hz,
      making them the fastest vertebrate muscles. Like other vertebrate muscle, these
      sonic muscles are "synchronous," necessitating that calcium be released and
      resequestered by the sarcoplasmic reticulum during each contraction cycle. Thus
      to operate at such high frequencies, vertebrate sonic muscles require extreme
      adaptations. We have found that to generate the "boatwhistle" mating call
      (approximately 200 Hz), the swimbladder muscle fibers of toadfish have evolved
      (i) a large and very fast calcium transient, (ii) a fast crossbridge detachment
      rate, and (iii) probably a fast kinetic off-rate of Ca2+ from troponin. The
      fibers of the shaker muscle of rattlesnakes have independently evolved similar
      traits, permitting tail rattling at approximately 90 Hz.

PMID- 8755611
TI  - Cytosolic Na+ controls and epithelial Na+ channel via the Go guanine nucleotide
      binding regulatory protein.
AB  - In tight Na+-absorbing epithelial cells, the fate of Na+ entry through amiloride
      sensitive apical membrane Na+ channels is matched to basolateral Na+ extrusion so
      that cell Na+ concentration and volume remain steady. Control of this process by
      regulation of apical Na+ channels has been attributed to changes in cytosolic
      Ca2+ concentration or pH, secondary to changes in cytosolic Na+ concentration,
      although cytosolic Cl- seems also to be involved. Using mouse mandibular gland
      duct cells, we now demonstrate that increasing cytosolic Na+ concentration
      inhibits apical Na+ channels independent of changes in cytosolic Ca2+, pH, or Cl
      , and the effect is blocked by GDP-beta-S, pertussis toxin, and antibodies
      against the alpha-subunits of guanine nucleotide-binding regulatory proteins
      (Go). In contrast, the inhibitory effect of cytosolic anions is blocked by
      antibodies to inhibitory guanine nucleotide-binding regulatory proteins (Gi1/Gi2.
      It thus appears that apical Na+ channels are regulated by Go and Gi proteins, the
      activities of which are controlled, respectively, by cytosolic Na+ and Cl-.

PMID- 8755610
TI  - Formation of junctions involved in excitation-contraction coupling in skeletal
      and cardiac muscle.
AB  - During excitation-contraction (e-c) coupling of striated muscle, depolarization
      of the surface membrane is converted into Ca2+ release from internal stores. This
      process occurs at intracellular junctions characterized by a specialized
      composition and structural organization of membrane proteins. The coordinated
      arrangement of the two key junctional components--the dihydropyridine receptor
      (DHPR) in the surface membrane and the ryanodine receptor (RyR) in the
      sarcoplasmic reticulum--is essential for their normal, tissue-specific function
      in e-c coupling. The mechanisms involved in the formation of the junctions and a
      potential participation of DHPRs and RyRs in this process have been subject of
      intensive studies over the past 5 years. In this review we discuss recent
      advances in understanding the organization of these molecules in skeletal and
      cardiac muscle, as well as their concurrent and independent assembly during
      development of normal and mutant muscle. From this information we derive a model
      for the assembly of the junctions and the establishment of the precise structural
      relationship between DHPRs and RyRs that underlies their interaction in e-c
      coupling.

PMID- 8755612
TI  - Genetic separation of tumor growth and hemorrhagic phenotypes in an estrogen
      induced tumor.
AB  - Chronic administration of estrogen to the Fischer 344 (F344) rat induces growth
      of large, hemorrhagic pituitary tumors. Ten weeks of diethylstilbestrol (DES)
      treatment caused female F344 rat pituitaries to grow to an average of 109.2 +/-
      6.3 mg (mean +/- SE) versus 11.3 +/- 1.4 mg for untreated rats, and to become
      highly hemorrhagic. The same DES treatment produced no significant growth (8.9 +/
      0.5 mg for treated females versus 8.7 +/- 1.1 for untreated females) or
      morphological changes in Brown Norway (BN) rat pituitaries. An F1 hybrid of F344
      and BN exhibited significant pituitary growth after 10 weeks of DES treatment
      with an average mass of 26.3 +/- 0.7 mg compared with 8.6 +/- 0.9 mg for
      untreated rats. Surprisingly, the F1 hybrid tumors were not hemorrhagic and had
      hemoglobin content and outward appearance identical to that of BN. Expression of
      both growth and morphological changes is due to multiple genes. However, while
      DES-induced pituitary growth exhibited quantitative, additive inheritance, the
      hemorrhagic phenotype exhibited recessive, epistatic inheritance. Only 5 of the
      160 F2 pituitaries exhibited the hemorrhagic phenotype; 36 of the 160 F2
      pituitaries were in the F344 range of mass, but 31 of these were not hemorrhagic,
      indicating that the hemorrhagic phenotype is not merely a consequence of
      extensive growth. The hemorrhagic F2 pituitaries were all among the most massive,
      indicating that some of the genes regulate both phenotypes.

PMID- 8755613
TI  - A rice homeobox gene, OSH1, is expressed before organ differentiation in a
      specific region during early embryogenesis.
AB  - Homeobox genes encode a large family of homeodomain proteins that play a key role
      in the pattern formation of animal embryos. By analogy, homeobox genes in plants
      are thought to mediate important processes in their embryogenesis, but there is
      very little evidence to support this notion. Here we described the temporal and
      spatial expression patterns of a rice homeobox gene, OSH1, during rice
      embryogenesis. In situ hybridization analysis revealed that in the wild-type
      embryo, OSH1 was first expressed at the globular stage, much earlier than
      organogenesis started, in a ventral region where shoot apical meristem and
      epiblast would later develop. This localized expression of OSH1 indicates that
      the cellular differentiation has already occurred at this stage. At later stages
      after organogenesis had initiated, OSH1 expression was observed in shoot apical
      meristem [except in the L1 (tunica) layer], epiblast, radicle, and their
      intervening tissues in descending strength of expression level with embryonic
      maturation. We also performed in situ hybridization analysis with a rice
      organless embryo mutant, orl1, that develops no embryonic organs. In the orl1
      embryo, the expression pattern of OSH1 was the same as that in the wild-type
      embryo in spite of the lack of embryonic organs. This shows that OSH1 is not
      directly associated with organ differentiation, but may be related to a
      regulatory process before or independent of the organ determination. The results
      described here strongly suggest that, like animal homeobox genes, OSH1 plays an
      important role in regionalization of cell identity during early embryogenesis.

PMID- 8755615
TI  - Action spectra for phytochrome A- and B-specific photoinduction of seed
      germination in Arabidopsis thaliana.
AB  - We have examined the seed germination in Arabidopsis thaliana of wild type (wt),
      and phytochrome A (PhyA)- and B (PhyB)-mutants in terms of incubation time and
      environmental light effects. Seed germination of the wt and PhyA-null mutant
      (phyA) was photoreversibly regulated by red and far-red lights of 10-1,000
      micromol m-2 when incubated in darkness for 1-14 hr, but no germination occurred
      in PhyB-null mutant (phyB). When wt seeds and the phyB mutant seeds were
      incubated in darkness for 48 hr, they synthesized PhyA during dark incubation and
      germinated upon exposure to red light of 1-100 nmol m-2 and far-red light of 0.5
      10 micromol m-2, whereas the phyA mutant showed no such response. The results
      indicate that the seed germination is regulated by PhyA and PhyB but not by other
      phytochromes, and the effects of PhyA and PhyB are separable in this assay. We
      determined action spectra separately for PhyA- and PhyB-specific induction of
      seed germination at Okazaki large spectrograph. Action spectra for the PhyA
      response show that monochromatic 300-780 nm lights of very low fluence induced
      the germination, and this induction was not photoreversible in the range
      examined. Action spectra for the PhyB response show that germination was
      photoreversibly regulated by alternate irradiations with light of 0.01-1 mmol m-2
      at wavelengths of 540-690 nm and 695-780 nm. The present work clearly
      demonstrated that PhyA photoirreversibly triggers the germination upon
      irradiations with ultraviolet, visible and far-red light of very low fluence,
      while PhyB controls the photoreversible effects of low fluence.

PMID- 8755614
TI  - Changes in voltage activation, Cs+ sensitivity, and ion permeability in H5
      mutants of the plant K+ channel KAT1.
AB  - KAT1 is a voltage-dependent inward rectifying K+ channel cloned from the higher
      plant Arabidopsis thaliana [Anderson, J. A., Huprikar, S. S., Kochian, L. V.,
      Lucas, W. J. & Gaber, R. F. (1992) Proc. Natl. Acad. Sci. USA 89, 3736-3740]. It
      is related to the Shaker superfamily of K+ channels characterized by six
      transmembrane spanning domains (S1-S6) and a putative pore-forming region between
      S5 and S6 (H5). The 115 region between Pro-247 and Pro-271 in KAT1 contains 14
      additional amino acids when compared with Shaker [Aldrich, R. W. (1993) Nature
      (London) 362, 107-108]. We studied various point mutations introduced into H5 to
      determine whether voltage-dependent plant and animal K+ channels share similar
      pore structures. Through heterologous expression in Xenopus oocytes and voltage
      clamp analysis combined with phenotypic analysis involving a potassium transport
      defective Saccharomyces cerevisiae strain, we investigated the selectivity filter
      of the mutants and their susceptibility toward inhibition by cesium and calcium
      ions. With respect to electrophysiological properties, KAT1 mutants segregated
      into three groups: (i) wild-type-like channels, (ii) channels modified in
      selectivity and Cs+ or Ca2+ sensitivity, and (iii) a group that was additionally
      affected in its voltage dependence. Despite the additional 14 amino acids in H5,
      this motif in KAT1 is also involved in the formation of the ion-conducting pore
      because amino acid substitutions at Leu-251, Thr-256, Thr-259, and Thr-260
      resulted in functional channels with modified ionic selectivity and inhibition.
      Creation of Ca2+ sensitivity and an increased susceptibility to Cs+ block through
      mutations within the narrow pore might indicate that both blockers move deeply
      into the channel. Furthermore, mutations close to the rim of the pore affecting
      the half-activation potential (U1/2) indicate that amino acids within the pore
      either interact with the voltage sensor or ion permeation feeds back on gating.

PMID- 8755616
TI  - An anion channel in Arabidopsis hypocotyls activated by blue light.
AB  - A rapid, transient depolarization of the plasma membrane in seedling stems is one
      of the earliest effects of blue light detected in plants. It appears to play a
      role in transducing blue light into inhibition of hypocotyl (stem) elongation,
      and perhaps other responses. The possibility that activation of a Cl- conductance
      is part of the depolarization mechanism was raised previously and addressed here.
      By patch clamping hypocotyl cells isolated from dark-grown (etiolated)
      Arabidopsis seedlings, blue light was found to activate an anion channel residing
      at the plasma membrane. An anion-channel blocker commonly known as NPPB 15-nitro
      2-(3-phenylpropylamino)-benzoic acid] potently and reversibly blocked this anion
      channel. NPPB also blocked the blue-light-induced depolarization in vivo and
      decreased the inhibitory effect of blue light on hypocotyl elongation. These
      results indicate that activation of this anion channel plays a role in
      transducing blue light into growth inhibition.

PMID- 8755617
TI  - Preferential expression of an ammonium transporter and of two putative nitrate
      transporters in root hairs of tomato.
AB  - Root hairs as specialized epidermal cells represent part of the outermost
      interface between a plant and its soil environment. They make up to 70% of the
      root surface and, therefore, are likely to contribute significantly to nutrient
      uptake. To study uptake systems for mineral nitrogen, three genes homologous to
      Arabidopsis nitrate and ammonium transporters (AtNrt1 and AtAmt1) were isolated
      from a root hair-specific tomato cDNA library. Accumulation of LeNrt1-1, LeNrt1
      2, and LeAmt1 transcripts was root-specific, with no detectable transcripts in
      stems or leaves. Expression was root cell type-specific and regulated by nitrogen
      availability. LeNrt1-2 mRNA accumulation was restricted to root hairs that had
      been exposed to nitrate. In contrast, LeNrt1-1 transcripts were detected in root
      hairs as well as other root tissues under all nitrogen treatments applied.
      Analogous to LeNrt1-1, the gene LeAmt1 was expressed under all nitrogen
      conditions tested, and root hair-specific mRNA accumulation was highest following
      exposure to ammonium. Expression of LeAMT1 in an ammonium uptake-deficient yeast
      strain restored growth on low ammonium medium, confirming its involvement in
      ammonium transport. Root hair specificity and characteristics of substrate
      regulation suggest an important role of the three genes in uptake of mineral
      nitrogen.

PMID- 8755619
TI  - Identification of a cDNA for a human high molecular-weight B-cell growth factor.

PMID- 8755618
TI  - Identification of transferred DNA insertions within Arabidopsis genes involved in
      signal transduction and ion transport.
AB  - The transferred DNA (T-DNA) of Agrobacterium tumefaciens serves as an insertional
      mutagen once integrated into a host plant's genome. As a means of facilitating
      reverse genetic analysis in Arabidopsis thaliana, we have developed a method that
      allows one to search for plants carrying F-DNA insertions within any sequenced
      Arabidopsis gene. Using PCR, we screened a collection of 9100 independent T-DNA
      transformed Arabidopsis lines and found 17 T-DNA insertions within the 63 genes
      analyzed. The genes surveyed include members of various gene families involved in
      signal transduction and ion transport. As an example, data are shown for a T-DNA
      insertion that was found within CPK-9, a member of the gene family encoding
      calmodulin-domain protein kinases.

PMID- 8755620
TI  - Vascular movement of plant viruses.

PMID- 8755621
TI  - MPG1, a gene encoding a fungal hydrophobin of Magnaporthe grisea, is involved in
      surface recognition.
AB  - Upon encountering a leaf surface, emergent germ tubes from conidia of the rice
      blast fungus, Magnaporthe grisea, form infection structures called appressoria
      that allow direct penetration of plant cells. The MPG1 gene encodes a fungal
      hydrophobin of M. grisea that is expressed during development of aerial hyphae,
      conidia, and appressoria. Deletion of MPG1 reduces the efficiency of appressorium
      formation. We found that yeast extract repressed MPG1 expression in vitro and
      inhibited appressorium development of the rice pathogen, strain Guy11.
      Appressorium formation of mpg1 mutants is rescued in trans by coinoculation with
      wild-type cells. MPG1 is required for efficient induction of appressoria in
      response to a host surface or highly hydrophobic artificial substrates. However,
      we identified several artificial substrates that can support efficient
      appressorium formation of mpg1 strains. This finding suggests that Mpg1p is not
      specifically required for appressorium formation, but is involved in the
      interaction with, and recognition of, the host surface. Additionally, a time
      window of competence to form appressoria was identified; the decision to form
      appressoria occurs approximately 6 to 8 h following conidial germination. After
      this critical time, cells are no longer able to form appressoria in response to
      inductive cues. These studies indicate that MPG1 hydrophobin is required for host
      recognition and that it acts as a morphogenetic signal for cellular
      differentiation.

PMID- 8755622
TI  - Proteins from cells of Rhizobium fredii bind to DNA sequences precedingnolX, a
      flavonoid-inducible nod gene that is not associated with a nod box.
AB  - Rhizobium fredii strains USDA257 and USDA191 both contain a set of nodulation
      genes termed nolXWBTUV. In the USDA257 background, nolX prevents infection of
      soybean cultivars such as McCall, and in both backgrounds, it blocks nodulation
      of Erythrina spp. We report here that expression of nolX is differentially
      responsive to a panel of flavonoids, and that the most potent inducers are also
      the most active inducers of nodC, a conventional, nod box-associated gene. Cell
      free protein extracts from uninduced and flavonoid-induced cells of strains
      USDA191 and USDA257 retard the electrophoretic mobility of DNA sequences that lie
      upstream of nolX. Binding is dependent both on nodD1 and nodD2, and it is
      abolished by the presence of a double-stranded, 23-bp oligonucleotide that lies
      within a 114-bp TaqI/SacII restriction fragment. This oligomer has significant
      sequence homology to A3, a putative negative regulatory element from
      R.leguminosarum bv. viciae. Deletion of the A3-homologous sequences elevates the
      basal and flavonoid-inducible expression of nolX by about 50%.

PMID- 8755623
TI  - Four Arabidopsis RPP loci controlling resistance to the Noco2 isolate of
      Peronospora parasitica map to regions known to contain other RPP recognition
      specificities.
AB  - Interactions between Arabidopsis thaliana and the downy mildew fungus Peronospora
      parasitica provide a model system to study the genetic and molecular basis of
      plant-pathogen recognition. With the use of the Noco2 isolate of P. parasitica,
      the reaction phenotypes of 46 accessions of Arabidopsis were examined and 31
      accessions exhibited resistance. Resistance phenotypes examined ranged from
      distinct necrotic pits or flecks to a weak necrosis accompanied by late and
      sparse fungal sporulation. Segregating populations generated from crosses between
      the susceptible accession Col-0 and the resistant accessions Ws-0, Pr-0, Oy-0, Po
      1, Bch-1, Ge-1, Di-1, Ji-1, and Te-0 were also screened with Noco2. The genetic
      data were consistent with the presence of single resistance (RPP) loci in all of
      these accessions except Oy-0, in which resistance was inherited as a digenic
      trait. As a first step to molecular cloning, the map positions of four resistance
      loci were determined. These have been designated RPP14.1 from Ws-0, RPP14.2 from
      Pr-O, and RPP14.3 and RPP5.2 from Oy-0. RPP14.1 was mapped to a 3.2-cM interval
      on chromosome 3 that is linked to a region between the markers Gl-1 and m249
      known to contain other P. parasitica resistance specificities. RPP14.2 from Pr-0
      and RPP14.3 from Oy-0 were also positioned in this interval. Moreover, RPP14.1
      and RPP14.2 showed linkage of < 0.05 cM, suggesting possible allelism. The second
      RPP locus from Oy-0, RPP5.2, was located on chromosome 4 and exhibited strong
      linkage (< 2 cM) to RRP5.1, a locus previously identified in the Arabidopsis
      accession Landsberg-erecta. The results reinforce evidence for RPP gene
      clustering in the Arabidopsis genome and provide new targets for cloning and
      examination of RPP gene structure, function, allelic variation, and organization
      within defined loci.

PMID- 8755624
TI  - Expression of the pisatin detoxifying genes (PDA) of Nectria haematococca in
      vitro and in planta.
AB  - The phytopathogenic fungus Nectria haematococca detoxifies pisatin, a phytoalexin
      produced by pea. Pisatin demethylating ability (a phenotype called Pda) is due to
      pisatin demethylase (pdm) and the genes encoding this enzyme are called PDA. Some
      isolates rapidly acquire a high to moderate rate of pisatin demethylating
      activity culture in response to pisatin (phenotypes PdaSH and PdaSM), while other
      isolates only slowly demethylate pisatin (phenotype PdaLL). Here we report that
      PDA-specific RNA levels increased more quickly in response to pisatin in isolates
      with PDA genes confering a PdaSH or PdaSM phenotype than in isolates with gene
      conferring a PdaLL phenotype. In addition, the pdm activity of transformants of
      N. haematococca containing chimeric constructs of PDASH and PDALL genes in which
      the 5' regulatory regions of these genes had been switched supports the
      conclusion that differential expression of PDA genes is responsible for the
      different Pda phenotypes detected in vitro. Northern analysis of pea tissue
      infected with isolates carrying PDASH or PDALL genes indicated that differential
      induction of these genes also occurred in planta. Only PDASH-specific RNA is
      readily detected in tissue infected with isolates containing PDASH and PDALL
      genes. Recently a pisatin biosynthetic gene, isoflavone reductase (IFR), has been
      identified. Using the polymerase chain reaction, qualitative detection of IFR and
      PDASH transcripts in infected tissue were made to assess the relative timing of
      these genes' expression. No transcripts were detected 6 h after inoculation, but
      transcripts of both genes were detected a 12 h, suggesting an interplay between
      the regulatory systems controlling the plants's defense response and the
      pathogen's counter response.

PMID- 8755625
TI  - Isolation and characterization of Rhizobium tropici Nod factor sulfation genes.
AB  - Rhizobium tropici produces a mixture of sulfated and non-sulfated Nod factors.
      The genes responsible for the sulfation process in R. tropici strain CFN299 were
      cloned and sequenced. These genes are homologous to the nodP, nodQ, and nodH
      genes from R. meliloti. The identity among the two species is 75% for nodP, 74%
      for nodQ, and 69% for nodH. NodH resembles sulfotransferases in general and NodQ
      has the characteristic purine-binding motifs and the PAPS 3'-phosphoadenosine 5'
      phosphosulfate) motif. Mutants of NodP and NodH were obtained by site-directed
      mutagenesis. They are no longer able to synthesize the sulfated Nod factor, as
      was demonstrated in high-pressure liquid chromatography and thin-layer
      chromatography assays. The NodP- mutant had a decreased nodulation capacity in
      Phaseolus vulgaris Negro Xamapa bean plants. In contrast, NodH- and NodP- mutants
      acquired an increased capacity to nodulate the high-nitrogen-fixing bean
      cultivars N-8-116 and BAT-477. Nodulation was restored to normal levels when the
      mutants were complemented with a 16-kb clone carrying the wild-type genes. The
      role of the sulfate on Nod factors in R. tropici was dependent on the bean
      cultivar and the conditions assayed.

PMID- 8755626
TI  - Isolation and expression of a host response gene family encoding thaumatin-like
      proteins in incompatible oat-stem rust fungus interactions.
AB  - Four cDNA clones (corresponding to tlp-1, -2, -3, and -4 genes) encoding
      thaumatin-like (TL), pathogenesis-related proteins were isolated from oat (Avena
      sativa) infected by an incompatible isolate Pga-1H of the oat stem rust fungus
      (Puccinia graminis f. sp. avenae). All four cDNA clones contained an open reading
      frame predicted to encode a 169-amino acid polypeptide with a signal peptide of
      21 amino acids at the N-terminus, suggesting that these proteins are transported
      through a secretory pathway. The amino acid sequences revealed high homology
      among the four cDNA clones, 80 to 99% identity and 86 to 100% similarity. The tlp
      genes and several TL protein genes of certain cereals are clustered into a small
      group that is phylogenetically separate from the major group of TL protein genes
      of several plant species. In plants infected with the incompatible isolate Pga
      1H, or an inappropriate isolate Pgt-8D of P. graminis f. sp. tritici, high levels
      of tlp gene transcripts accumulated at 42 to 48 h AI and thereafter when
      hypersensitive host cell death occurred and hyphal growth was inhibited, whereas
      in plants infected with a compatible isolate Pga-6A, relatively lower amounts of
      transcripts were detected. Overall, transcript levels were higher with tlp-1 than
      with the three other genes. Spray with a light mineral oil used as a spore
      carrier induced transient expression of tlp-1, -2, and -3 genes at 16 to 30 h AI
      which obscured the initial induction of the tlp genes in response to infection by
      the pathogens. In contrast, tlp-4 was induced very little by oil spray, so that
      induction was clearly observed in response to either compatible, incompatible, or
      inappropriate isolates at 24 to 30 h AI. Wounding leaves by either slicing or
      puncturing them strongly induced tlp-1 and tlp-3, moderately induced tlp-2, but
      had no effect on tlp-4. Taken together, the results showed that tlp genes
      displayed differential responses to oil spray, mechanical wounding, and pathogen
      infection and that the expression of tlp genes, especially tlp-1, in oat is
      associated with resistance reactions in response to infection by incompatible and
      inappropriate isolates of the stem rust fungi.

PMID- 8755627
TI  - Sequence and mutational analysis of the common nodBCIJ region of Rhizobium sp.
      (Oxytropis arctobia) strain N33, a nitrogen-fixing microsymbiont of both arctic
      and temperate legumes.
AB  - By heterologous hybridization, we have identified the common nodulation genes
      nodBCIJ of Rhizobium sp. strain N33 within a 8.2-kb PstI fragment. The nodBCIJ
      genes are located within a 4,620-bp region which also included a consensus nod
      box promoter. The four open reading frames coding for the nodBCIJ genes contain
      657, 1,353, 915, and 789 nucleotides, respectively. We found that the nodA gene
      was not adjacent to the nodB gene, unlike the situation in many rhizobia. The DNA
      of the nodBCIJ genes of Rhizobium sp. strain N33 were found to be homologous to
      the corresponding genes of other rhizobia except for the 3'-coding region of the
      nodC gene. The deduced NodC protein was the longest of the rhizobia except
      Bradyrhizobium japonicum. Tn5 mutagenesis of the common nod region of strain N33
      revealed that the nodBC genes were essential for nodulation on their temperate
      hosts Onobrychis viciifolia and Astragalus cicer. By contrast, mutations in the
      nodI and nodJ genes produced a Nod+ phenotype with a reduced number of nodules on
      the temperate hosts. Nodules formed on Onobrychis viciifolia by either nodI or
      nodJ mutants were approximately 10 times smaller than nodules formed by the wild
      type strain: this reduction in nodule size was not observed on Astragalus cicer.

PMID- 8755628
TI  - The third beta is not the charm.

PMID- 8755629
TI  - Mammalian type 2 deiodinase sequences: finally, the end of the beginning.

PMID- 8755630
TI  - 1H-NMR detectable fatty acyl chain unsaturation in excised leiomyosarcoma
      correlate with grade and mitotic activity.
AB  - We report on the use of 1H-NMR two-dimensional total correlated spectroscopy (2D
      TOCSY) at 600 MHz for an ex vivo analysis of fatty acyl chain lipid in normal
      smooth muscle and a series of primary retroperitoneal leiomyosarcomas. These
      TOCSY spectra were used to identify and quantitate the methylene protons situated
      between unsaturated site protons (D) to those bordered by only one unsaturated
      site proton (C). The D/C cross-peak volume ratios determined for oleic (18:1),
      linoleic (18:2), linolenic (18:3), and arachidonic (20:4) acids were 0.0, 1.3,
      2.7, and 4.0, respectively, suggesting that this ratio can be a measure of the
      degree of unsaturation for fatty acyl chains of lipids. The D/C cross-peak volume
      ratio was found to be proportional to the mean mitotic activity (r = 0.94) in
      nine smooth muscle tissues. These results suggest, that for leiomyosarcoma, the
      degree of fatty acyl unsaturation may be an important determinant of the
      metastatic potential of these tumors. Furthermore, application of TOCSY for the
      ex vivo study of smooth muscle tumors would potentially serve as a pathologist
      independent and quantitative method for assessment of leiomyosarcoma grade and
      mitotic activity thereby rendering a more accurate staging of patients.

PMID- 8755631
TI  - The expression of ob gene is not acutely regulated by insulin and fasting in
      human abdominal subcutaneous adipose tissue.
AB  - The regulation of ob gene expression in abdominal subcutaneous adipose tissue was
      investigated using a reverse transcription-competitive PCR method to quantify the
      mRNA level of leptin. Leptin mRNA level was highly correlated with the body mass
      index of 26 subjects (12 lean, 7 non-insulin-dependent diabetic, and 7 obese
      patients). The effect of fasting on ob gene expression was investigated in 10
      subjects maintained on a hypocaloric diet (1045 KJ/d) for 5 d. While their
      metabolic parameters significantly changed (decrease in insulinemia, glycemia,
      and resting metabolic rate and increase in plasma ketone bodies), the caloric
      restriction did not modify the leptin mRNA level in the adipose tissue. To verify
      whether insulin regulates ob gene expression, six lean subjects underwent a 3-h
      euglycemic hyperinsulinemic (846 +/- 138 pmol/liter) clamp. Leptin and Glut 4
      mRNA levels were quantified in adipose tissue biopsies taken before and at the
      end of the clamp. Insulin infusion produced a significant threefold increase in
      Glut 4 mRNA while leptin mRNA was not affected. It is concluded that ob gene
      expression is not acutely regulated by insulin or by metabolic factors related to
      fasting in human abdominal subcutaneous adipose tissue.

PMID- 8755632
TI  - Association and cosegregation of stroke with impaired endothelium-dependent
      vasorelaxation in stroke prone, spontaneously hypertensive rats.
AB  - While hypertension is a major risk factor for stroke, it is not its sole
      determinant. Despite similar blood pressures, spontaneously hypertensive rats
      (SHR) do not share the predisposition to cerebrovascular disease typical of
      stroke-prone spontaneously hypertensive rats (SHRSP). We investigated vascular
      function in male SHR and SHRSP as well as in SHRSP/SHR-F2 hybrid animals. Animals
      were maintained on the appropriate dietary regimen necessary for the
      manifestation of stroke. Among the hybrid animals, a group of stroke-prone and a
      group of stroke-resistant rats were selected. Blood pressure was similar in all
      groups. Endothelium-independent vascular reactivity tested on isolated rings of
      thoracic aorta and basilar artery after death showed similar contractile and
      dilatory responses to serotonin and nitroglycerin, respectively, in all groups.
      In contrast, endothelium-dependent relaxation, in response to acetylcholine or
      substance P, was markedly reduced in SHRSP compared with SHR. Similarly, reduced
      vasodilatory responses were present in aortae of F2 rats that had suffered a
      stroke when compared with SHR or F2 rats resistant to stroke. The observed
      association and cosegregation of stroke with significant and specific impairment
      of endothelium-dependent vasorelaxation among SHRSP and stroke-prone F2 hybrids,
      respectively, suggest a potential causal role of altered endothelium-dependent
      vascular relaxation in the pathogenesis of stroke.

PMID- 8755633
TI  - Suppression of mesangial proliferative glomerulonephritis development in rats by
      inhibitors of cAMP phosphodiesterase isozymes types III and IV.
AB  - Excessive mesangial cell (MC) proliferation is a hallmark of many
      glomerulopathies. In our recent study on cultured rat MC (Matousovic, K., J.P.
      Grande, C.C.S. Chini, E.N. Chini, and T.P. Dousa. 1995. J. Clin. Invest. 96:401
      410) we found that inhibition of isozyme cyclic-3',5'-nucleotide
      phosphodiesterase (PDE) type III (PDE-III) suppressed MC mitogenesis by
      activating cAMP-dependent protein kinase (PKA) and by decreasing activity of
      mitogen-activated protein kinase (MAPK). We also found that inhibition of another
      PDE isozyme, PDE-IV, suppresses superoxide generation in glomeruli (Chini,
      C.C.S., E.N. Chini, J.M. Williams, K. Matousovic, and T.P. Dousa. 1994. Kidney
      Int. 46:28-36). We thus explored whether administration in vivo of the selective
      PDE-III antagonist, lixazinone (LX), together with the specific PDE-IV
      antagonist, rolipram (RP), can attenuate development of mesangioproliferative
      glomerulonephritis (MSGN) induced in rats by anti-rat thymocyte serum (ATS).
      Unlike the vehicle-treated MSGN rats, rats with MSGN treated with LX and RP did
      not develop proteinuria and maintained normal renal function when examined 5 d
      after injection of ATS. In PAS-stained kidneys from PDE-antagonists-treated MSGN
      rats the morphology of glomeruli showed a reduction in cellularity compared with
      control rats with ATS. Compared with MSGN rats receiving vehicle, the MSGN rats
      receiving PDE-antagonists had less glomerular cell proliferation (PCNA delta 
      65%), a significantly lesser macrophage infiltration (delta -36% ED-1) and a
      significant reduction of alpha-smooth muscle actin expression by activated MC; in
      contrast, immunostaining for platelet antigens and laminin were not different.
      The beneficial effect of PDE inhibitors was not due to a moderate decrease
      (approximately -20%) in systolic blood pressure (SBP); as a similar decrease in
      SBP due to administration of hydralazine, a drug devoid of PDE inhibitory effect,
      did not reduce severity of MSGN in ATS-injected rats. We conclude that
      antagonists of PDE-III and PDE-IV administered in submicromolar concentrations in
      vivo to ATS-injected rats can decrease the activation and proliferation of MC,
      inhibit the macrophage accumulation, and prevent proteinuria in the acute phase
      of MSGN. We propose that PDE isozyme inhibitors act to block (negative
      "crosstalk") the mitogen-stimulated intracellular signaling pathway which
      controls MC proliferation due to activating of the cAMP-PKA pathway. These
      results suggest that antagonists of PDE-111 and IV may have a suppressive effect
      in acute phases or relapses of glomerulopathies associated with MC
      proliferations.

PMID- 8755634
TI  - Therapeutic effect of the anti-Fas antibody on arthritis in HTLV-1 tax transgenic
      mice.
AB  - We have recently demonstrated Fas-mediated apoptosis in the synovium, of patients
      with rheumatoid arthritis (RA) and suggested that it may be one factor
      responsible for the regression of RA. To examine whether the induction of
      apoptosis caused by anti-Fas mAb may play a potential role as a new therapeutic
      strategy for RA, we investigated the effect of anti-Fas mAb (RK-8) on synovitis
      in an animal model of RA, the human T cell leukemia virus type I (HTLV-1) tax
      transgenic mice. We report here that administration of anti-Fas mAb into mice
      intra-articularly improved the paw swelling and arthritis within 48 h.
      Immunohistochemical study and in vitro culture studies showed that 35% of
      synovial fibroblasts, 75% of mononuclear cells, and some of polymorphonuclear
      leukocytes infiltrating in synovium underwent apoptosis by anti-Fas mAb. In situ
      nick end labeling analysis and electron microscope analysis clearly showed that
      many cells in synovium were induced apoptosis by anti-Fas mAb administration.
      However, local administration of anti-Fas mAb did not produce systemic side
      effects. Results demonstrated that administration of anti-Fas mAb in arthritic
      joints of the HTLV-1 tax transgenic mice produced improvement of arthritis. These
      findings suggest that local administration of anti-Fas mAb may represent a useful
      therapeutic strategy for proliferative synovitis such as RA.

PMID- 8755635
TI  - Clonal T cell responses in tumor infiltrating lymphocytes from both regressive
      and progressive regions of primary human malignant melanoma.
AB  - The T cell receptor (TCR) BV variable (V) gene repertoire of tumor infiltrating
      lymphocytes (TIL) found in progressive and regressive regions of the same primary
      human melanomas were characterized by reverse transcription coupled polymerase
      chain reaction (RT-PCR). After surgery, the tumors were divided into different
      parts which were judged as regressive or progressive regions by visual
      inspection. Subsequently this diagnosis was confirmed by histology. From a total
      of four primary melanomas analyzed, 2 were drawn to be HLA-A2+. Only relatively
      few BV-gene families were expressed at significant levels in each of the samples.
      Comparison of the BV-expression in regressive versus progressive regions of the
      same tumor revealed major differences in all cases examined. Direct sequencing of
      RT-PCR products indicated that highly expressed BV-gene families were of clonal
      origin in both the regressive and progressive regions. Together, these data
      strongly suggest the occurrence of clonal T cell responses in both regressive and
      progressive areas of the same primary tumor. The differences in expression of
      certain BV-genes may correlate with the functional activity of certain
      populations of tumor-infiltrating T cells.

PMID- 8755636
TI  - Defective cystathionine beta-synthase regulation by S-adenosylmethionine in a
      partially pyridoxine responsive homocystinuria patient.
AB  - We determined the molecular basis of cystathionine beta-synthase (CBS) deficiency
      in a partially pyridoxine-responsive homocystinuria patient. Direct sequencing of
      the entire CBS cDNA revealed the presence of a homozygous G1330A transition. This
      mutation causes an amino acid change from aspartic acid to asparagine (D444N) in
      the regulatory domain of the protein and abolishes a TaqI restriction site at DNA
      level. Despite the homozygous mutation, CBS activities in extracts of cultured
      fibroblasts of this patient were not in the homozygous but in the heterozygous
      range. Furthermore, we observed no stimulation of CBS activity by S
      adenosylmethionine, contrary to a threefold stimulation in control fibroblast
      extract. The mutation was introduced in an E. coli expression system and CBS
      activities were measured after addition of different S-adenosylmethionine
      concentrations (0-200 microM). Again, we observed a defective stimulation of CBS
      activity by S-adenosylmethionine in the mutated construct, whereas the normal
      construct showed a threefold stimulation in activity. These data suggest that
      this D444N mutation interferes in S-adenosylmethionine regulation of CBS.
      Furthermore, it indicates the importance of S-adenosylmethionine regulation of
      the transsulfuration pathway in homocysteine homeostasis in humans.

PMID- 8755637
TI  - IgM-producing chronic lymphocytic leukemia cells undergo immunoglobulin isotype
      switching without acquiring somatic mutations.
AB  - The malignant B cells in chronic lymphocytic leukemia (CLL) typically express low
      density membrane IgM or IgM/IgD. In vitro experiments have shown that the CLL
      cells can be induced to differentiate into cells that secrete immunoglobulin (Ig)
      and can occasionally undergo heavy (H) chain class switching. We now show that
      the CLL cells also undergo isotype-switching in vivo, since gamma and/or alpha H
      chain transcripts with identical FW3/CDR3/FW4 regions as the mu CLL transcripts
      were detected in all of the 13 investigated patients with IgM+ CLL. In most cases
      switching had occurred to alpha1 and gamma3, but CLL transcripts corresponding to
      the other gamma chain isotypes were also detected. In one case both the
      productively and nonproductively rearranged allele were found to undergo H chain
      class switching. CLL gamma transcripts were also present in surface IgG+ sorted B
      cells, demonstrating that a small subset of the CLL cells express membrane IgG.
      In addition, transcripts encoding secretary gamma2 and gamma3 H chains were
      detected in two cases, which suggests that some serum IgG could be produced by
      the leukemic clone. Analysis of sorted PBL showed that isotype-switching occurs
      in CLL cells that express the CD5 antigen. Finally, nucleotide sequence analysis
      showed that the mu, alpha, and gamma CLL transcripts are identical, demonstrating
      that the CLL cells do not accumulate somatic mutations in their variable region
      genes after the H chain class switching. These data provide in vivo evidence that
      isotype-switching is a frequent phenomenon in CLL, and indicate that a subset of
      the CLL lymphocytes progress to later stages of B cell differentiation.

PMID- 8755639
TI  - Interactions between insulin-like growth factor-I (IGF-I) and the renin
      angiotensin system in follicular growth and ovulation.
AB  - The interactions between insulin-like growth factor-I (IGF-I) and the renin
      angiotensin system (RAS) in follicular growth and ovulation were studied with the
      use of an isolated perfused rabbit ovary preparation. Ovulation failed to occur
      in either control ovaries or the experimental ovaries perfused with IGF-I in a
      concentration of 1, 10, or 100 ng/ml in the absence of gonadotropin. Exposure to
      IGF-I stimulated the secretion rate of angiotensin II-like immunoreactivity (Ang
      II-IR) in perfused rabbit ovaries in a dose-dependent manner. The percent
      increase in follicle diameter in ovaries perfused with IGF-I for 12 h was
      significantly correlated with the secretion rate of Ang II-IR at 12 h after
      exposure to IGF-I. The addition of IGFBP-3 to the perfusate did not induce
      ovulation in the absence of gonadotropin, but exposure to IGFBP-3 inhibited hCG
      induced ovulation in a dose-dependent manner. In addition, IGFBP-3 significantly
      reduced the ovarian secretion rate of Ang II-IR and prostaglandins stimulated by
      hCG administration. Intrafollicular plasminogen activator (PA) activity
      significantly increased within 4 h after exposure to 100 ng/ml of IGF-I, compared
      with that in control ovaries perfused with medium alone. The concomitant addition
      of IGFBP-3 to the perfusate significantly reduced the IGF-I-stimulated PA
      activity in the preovulatory follicles at 4, 6, and 8 h after exposure to IGF-I.
      However, IGFBP-3 alone affected neither the ovarian secretion rate of Ang II-IR
      nor intrafollicular PA activity. Exposure to streptokinase, an exogenous PA, in
      vitro stimulated both follicular growth and the intrafollicular Ang II-IR
      content. In conclusion, IGF-I enhances both ovarian Ang II production and
      follicular development by stimulating intrafollicular PA activity.

PMID- 8755640
TI  - Adenoviral-mediated transfer of the human endothelial nitric oxide synthase gene
      reduces acute hypoxic pulmonary vasoconstriction in rats.
AB  - Nitric oxide (NO), a vasodilator involved in the regulation of pulmonary vascular
      tone, is synthesized by a family of enzymes, nitric oxide synthases (NOS). To
      investigate whether adenoviral-mediated overexpression of constitutive
      endothelial NOS (ceNOS) would attenuate hypoxic pulmonary vasoconstriction, we
      aerosolized 3 X 10(9) plaque forming units of a recombinant adenovirus containing
      the ceNOS gene (AdCMVceNOS) into rat lungs. Four days after infection, transgene
      expression was confirmed using immunoblot techniques. Diffuse ceNOS
      immunostaining was detected in alveoli and medium-sized and small pulmonary
      vessels of AdCMVceNOS-transduced lungs. AdCMVceNOS-transduction was associated
      with an 86% increase in [3H]arginine to [3H]citrulline conversion and a rise in
      pulmonary cGMP levels from 7 +/- 1 to 59 +/- 9 pmol/mg protein in lungs from
      AdCMVceNOS versus control rats, (P < 0.05). During acute hypoxia (FIO2 = 0.10)
      for 25 min, mean pulmonary artery pressure (PAP) increased significantly from 17
      +/- 1 to 27 +/- 1 mmHg in rats aerosolized with saline (n = 4) and from 18 +/- 1
      to 28 +/- 1 mmHg in rats given an adenoviral vector expressing a nuclear-targeted
      beta-galactosidase gene (AdCMV beta gal, n = 8). In contrast, in AdCMVceNOS
      transduced rats (n = 8) the hypoxia-induced increase in PAP was significantly
      attenuated (18 +/- 1 to 23 +/- 2 mmHg). Systemic blood pressure was not affected
      by aerosol gene transfer. Thus, adenoviral-mediated ceNOS gene transfer to rat
      lungs increases ceNOS expression and activity, and reduces acute hypoxic
      pulmonary vasoconstriction. Aerosolized recombinant adenovirus overexpressing
      vasodilatory proteins can act as a selective pulmonary vasodilator and may hold
      promise as a future therapeutic strategy for pulmonary hypertension.

PMID- 8755638
TI  - Viral infection induces dependence of neuronal M2 muscarinic receptors on
      cyclooxygenase in guinea pig lung.
AB  - Inhibitory M2 muscarinic receptors on parasympathetic nerve endings in the lungs
      decrease release of acetylcholine, inhibiting vagally induced
      bronchoconstriction. Neuronal M2 receptor function can be studied using selective
      agonists and antagonists such as pilocarpine and gallamine. In pathogen-free
      guinea pigs indomethacin (1 mg/kg) did not alter the effect of either gallamine
      or pilocarpine, thus in pathogen free animals neuronal M2 muscarinic receptors
      function independently of cyclooxygenase products. However, in guinea pigs
      infected with virus, (which causes temporary loss of M2 receptor function), and
      then allowed to recover for 8 wk (to allow recovery of M2 receptors),
      indomethacin prevented both gallamine's potentiation and pilocarpine's inhibition
      of vagally induced bronchoconstriction. This new effect of indomethacin was not
      blocked by the addition of a 5-lipoxygenase inhibitor, AA861. However, the
      selective COX II inhibitor, L-745,337, had the same effect as indomethacin. Since
      exposure to ozone also caused neuronal M2 receptors to become dependent upon
      cyclooxygenase the effects of viral infection are likely to be due to
      inflammation. Thus, despite apparent recovery of normal M2 receptor function
      after viral infection or ozone, linkage of these receptors is chronically altered
      such that they become largely dependent on the activity of COX II.

PMID- 8755641
TI  - Renal expression of tissue factor pathway inhibitor and evidence for a role in
      crescentic glomerulonephritis in rabbits.
AB  - Tissue factor pathway inhibitor (TFPI) was demonstrated in the kidneys of normal
      rabbits and in a crescentic model of glomerulonephritis (GN), where fibrin is a
      key mediator of injury. In normal kidneys, TFPI was expressed in glomeruli, in
      intrarenal arteries and the interstitial capillary network. Evidence for TFPI
      synthesis in vivo was provided by in situ demonstration of TFPI mRNA in glomeruli
      and intrarenal vessels and by biosynthetic labeling of TFPI released from
      glomeruli in vitro. In fibrin-dependent crescentic GN, glomerular TFPI synthesis
      and expression was initially decreased (TFPI antigen at 24 h, 7.5 +/- 0.7
      ng/10(3) glomeruli; normal, 11.1 +/- 0.9 ng/10(3) glomeruli, P < 0.02) and
      subsequently returned to normal values. Plasma TFPI levels increased
      progressively throughout the evolution of disease. In vivo inhibition of TFPI
      using an anti-TFPI antibody during the development of GN significantly increased
      glomerular fibrin deposition (GFD) and exacerbated renal impairment. Infusion of
      recombinant human TFPI significantly reduced development of GFD (fibrin scores,
      TFPI treated 0.82 +/- 0.11, control 1.49 +/- 0.14, P < 0.01), proteinuria and
      renal impairment. This data indicates that TFPI is synthesized and expressed in
      normal glomeruli and is down regulated in the early response to glomerular
      injury. Endogenous glomerular TFPI and treatment with recombinant TFPI reduces
      GFD and injury in fibrin dependent GN. TFPI has the potential to be of
      therapeutic benefit in the management of fibrin dependent human GN.

PMID- 8755642
TI  - Inflammatory and hyperproliferative skin disease in mice that express elevated
      levels of the IL-1 receptor (type I) on epidermal keratinocytes. Evidence that IL
      1-inducible secondary cytokines produced by keratinocytes in vivo can cause skin
      disease.
AB  - Interleukin (IL)-1 induces a cascade of secondary cytokines in a large number of
      cell types in vitro, including monocytes, fibroblasts, synovial cells, and
      keratinocytes. Although it has been proposed that autocrine or paracrine
      activation of such cells by IL- 1 in situ could orchestrate a local inflammatory
      response, formal proof for such an hypothesis has been lacking. In an attempt to
      lower the threshold for secondary cytokine production in these cells in response
      to IL-1, we have generated transgenic mice (designated IR10) which overexpress
      functional type 1 IL-1 receptor in basal layer of epidermis keratinocytes. As
      predicted, keratinocytes from these animals were substantially more responsive to
      exogenous IL-1 than nontransgenic keratinocytes when stimulated in vitro. When
      challenged with known inducers of keratinocyte IL-1 synthesis and release, skin
      of IR10 mice exhibited an exaggerated inflammatory response, characterized by
      epidermal hyperplasia and an acute dermal inflammatory cell infiltrate. In this
      setting, the secondary epidermal cytokines gro-alpha and GM-CSF were strongly
      induced in transgenic epidermis but not in control skin. To confirm that these
      changes were indeed related to IL-1 mediated activation pathways, IR10 mice were
      crossed to a distinct line of transgenic mice that overexpress 17-kD IL-l alpha
      in basal keratinocytes. Double transgenic mice derived from this cross breeding
      experiment developed spontaneous inflammation of the skin, similar in appearance
      to that induced by PMA, both histologically and macroscopically, and distinct
      from that seen in either parental strain spontaneously. Furthermore, secondary
      cytokines were more strongly induced in the double transgenic than in either
      parental strain. These findings conclusively demonstrate the potential for
      functional autocrine pathways of keratinocyte activation mediated by IL-1 alpha
      in vivo, and suggest that level of expression of type 1 IL-1 receptor may
      function as a significant control point in physiologic IL-1 mediated autocrine
      pathways.

PMID- 8755643
TI  - Mitochondrial complex I deficiency leads to increased production of superoxide
      radicals and induction of superoxide dismutase.
AB  - Mitochondria were isolated from skin fibroblast cultures derived from healthy
      individuals (controls) and from a group patients with complex I (NADH-CoQ
      reductase) deficiency of the mitochondrial respiratory chain. The complex I
      deficient patients included those with fatal infantile lactic acidosis (FILA),
      cardiomyopathy with cataracts (CC), hepatopathy with tubulopathy (HT), Leigh's
      disease (LD), cataracts and developmental delay (CD), and lactic acidemia in the
      neonatal period followed by mild symptoms (MS). Production of superoxide
      radicals, on addition of NADH, were measured using the luminometric probe
      lucigenin with isolated fibroblast mitochondrial membranes. Superoxide production
      rates were highest with CD and decreased in the order CD >> MS > LD > control >
      HT > FILA = CC. The quantity of Mn-superoxide dismutase (MnSOD), as measured by
      ELISA techniques, however, was highest in CC and FILA and lowest in CD. Plots of
      MnSOD quantity versus superoxide production showed an inverse relationship for
      most conditions with complex I deficiency. We hypothesize that oxygen radical
      production is increased when complex I activity is compromised. However, the
      observed superoxide production rates are modulated by the variant induction of
      MnSOD which decreases the rates, sometimes below those seen in control fibroblast
      mitochondria. In turn, we show that the variant induction of MnSOD is most likely
      a function of the change in the redox state of the cell experienced rather than a
      result of the complex I defect per se.

PMID- 8755644
TI  - Mutations in exon 3 of the glycogen debranching enzyme gene are associated with
      glycogen storage disease type III that is differentially expressed in liver and
      muscle.
AB  - Glycogen storage disease type HI (GSD-III), an autosomal recessive disease, is
      caused by deficient glycogen debranching enzyme (GDE) activity. Most GSD-III
      patients are GDE deficient in both liver and muscle (type IIIa), and some GSD-III
      patients have GDE absent in liver but retained in muscle (type IIIb). The
      molecular basis for this enzymatic variability is largely unknown. In the present
      study, the analysis of the GDE gene in three GSD-IIIb patients by single-strand
      conformation polymorphism (SSCP), DNA sequencing, restriction analysis, and
      family studies, revealed each of them as being a compound heterozygote for two
      different mutations. The first mutant alleles in all three patients involved
      mutations in exon 3 at amino acid codon 6 of the GDE protein. Two had an AG
      deletion at nucleotides 17 and 18 of the GDE cDNA (17delAG) which resulted in
      change of subsequent amino acid sequence and a truncated protein (25X); the other
      had a C to T transition at nucleotide 16 of the cDNA which changed a Glutamine
      codon to a stop codon (Q6X). The 17delAG mutation was also found in 8 of the 10
      additional GSD-IIIb patients. The Q6X mutation was found in one of the remaining
      two GSD-IIIb patients. These two mutations were not found in any of the 31 GSD
      IIIa patients, 2 GSD-IIId patients, nor 28 unrelated normal controls. The second
      mutant alleles in each of the three GSD-IIIb patients were R864X, R1228X, and
      W68OX. The R864X and R1228X were not unique for GSD-IIIb as they were also found
      in GSD-IIIa patients (frequency of 10.3% and 5.2% in Caucasian patients,
      respectively). Our data demonstrated that both IIIa and IIIb had mutations in the
      same GDE gene and established for the first time the molecular basis of GSD-III
      that differentially expressed in liver and muscle. The striking and specific
      association of exon 3 mutations with GSD-IIIb may provide insight into mechanisms
      controlling tissue-specific expression of the GDE gene. The identification of
      exon 3 mutations has clinical significance as well because it distinguished GSD
      IIIb from IIIa hence permitting diagnosis from a blood sample rather than a more
      invasive muscle biopsy.

PMID- 8755645
TI  - An intronic mutation in a lariat branchpoint sequence is a direct cause of an
      inherited human disorder (fish-eye disease).
AB  - The first step in the splicing of an intron from nuclear precursors of mRNA
      results in the formation of a lariat structure. A distinct intronic nucleotide
      sequence, known as the branchpoint region, plays a central role in this process.
      We here describe a point mutation in such a sequence. Three sisters were shown to
      suffer from fish-eye disease (FED), a disorder which is caused by mutations in
      the gene coding for lecithin:cholesterol acyltransferase (LCAT). Sequencing of
      the LCAT gene of all three probands revealed compound heterozygosity for a
      missense mutation in exon 4 which is reported to underlie the FED phenotype, and
      a point mutation located in intron 4 (IVS4:T-22C). By performing in vitro
      expression of LCAT minigenes and reverse transcriptase PCR on mRNA isolated from
      leukocytes of the patient, this gene defect was shown to cause a null allele as
      the result of complete intron retention. In conclusion, we demonstrated that a
      point mutation in a lariat branchpoint consensus sequence causes a null allele in
      a patient with FED. In addition, our finding illustrates the importance of this
      sequence for normal human mRNA processing. Finally, this report provides a widely
      applicable strategy which ensures fast and effective screening for intronic
      defects that underlie differential gene expression.

PMID- 8755646
TI  - Liver cirrhosis induces renal and liver phospholipase A2 activity in rats.
AB  - Maintenance of renal function in liver cirrhosis requires increased synthesis of
      arachidonic acid derived prostaglandin metabolites. Arachidonate metabolites have
      been reported to be involved in modulation of liver damage. The purpose of the
      present study was to establish whether the first enzyme of the prostaglandin
      cascade synthesis, the phospholipase A2(PLA2) is altered in liver cirrhosis
      induced by bile duct excision. The mRNA of PLA2(group I and II) and annexin-I a
      presumptive inhibitor of PLA2 enzyme was measured by PCR using glyceraldehyde 3
      phosphate dehydrogenase (GAPDH) as an internal standard. The mean mRNA ratio of
      group II PLA2/GAPDH was increased in liver tissue by 126% (P < 0.001) and in
      kidney tissue by 263% (P < 0.006) following induction of liver cirrhosis. The
      increase in group II PLA2 mRNA in cirrhotic animals was reflected by an increase
      in PLA2 protein and enzyme activity in both liver and kidney tissues. Since the
      mRNA of group I PLA2 was not detectable and Group IV PLA2 activity measured in
      liver and kidney tissue samples was very low and not changed following induction
      of cirrhosis, it is likely that the major PLA2 activity measured in liver and
      kidney corresponds to group II PLA2 enzyme. The mean mRNA ratio of annexin
      I/GAPDH was increased in liver tissue by 115% (P < 0.05) but unchanged in kidney
      tissue following induction of cirrhosis. The protein content of annexin-I and -V
      were not affected by bile duct excision in liver and kidney tissue indicating
      that upregulation of group II PLA2 activity was not due to downregulation of
      annexin-I or -V. Group II PLA2 activity of glomerular mesangial cells stimulated
      by interleukin-1 beta was enhanced by bile juice and various bile salts. In
      conclusion, activity of group II PLA2 is upregulated partly due to enhanced
      transcription and translation in cirrhosis and is furthermore augmented by
      elevated levels of bile salts.

PMID- 8755647
TI  - Polymorphisms at the 5'-end of the apolipoprotein AI gene and severity of
      coronary artery disease.
AB  - Elevated HDL-cholesterol (C) and apo AI are associated with decreased coronary
      artery disease (CAD) risk. We determined distributions of two MspI polymorphisms
      of the apo AI gene, associated in other studies with increased HDL-C, among 644
      patients aged < or = 65 years in relation to circulating lipids and CAD severity
      assessed angiographically. The rare allele distributions at both sites were in
      Hardy-Weinberg equilibrium in these patients but the base changes were not
      associated with HDL-C and apo AI levels. However, patients homozygous for the -75
      bp substitution were more likely to have one or more significantly diseased
      vessels (> 50% luminal obstruction)(OR: 4.75, 95%CI: 1.10- 20.46) as also were
      patients with the rare +83 bp alleles (OR: 2.56, 95%CI: 1.13-5.81). While there
      was an additive effect of the two polymorphisms to have severe CAD (OR: 6.33,
      95%CI: 1.33-30.02), the polymorphism at +83 bp remained significant in predicting
      CAD severity after adjusting for other variables in a logistic regression
      analysis (OR: 2.95, 95%CI: 1.26-6.90), which was also strongly associated with
      the positive family CAD history (P = 0.009). We conclude that patients with these
      base changes in this Australian coronary population do not have increased HDL-C
      and apo AI levels but do have more severe CAD.

PMID- 8755648
TI  - Contributions of gluconeogenesis to glucose production in the fasted state.
AB  - Healthy subjects ingested 2H2O and after 14, 22, and 42 h of fasting the
      enrichments of deuterium in the hydrogens bound to carbons 2, 5, and 6 of blood
      glucose and in body water were determined. The hydrogens bound to the carbons
      were isolated in formaldehyde which was converted to hexamethylenetetramine for
      assay. Enrichment of the deuterium bound to carbon 5 of glucose to that in water
      or to carbon 2 directly equals the fraction of glucose formed by gluconeogenesis.
      The contribution of gluconeogenesis to glucose production was 47 +/- 49% after 14
      h, 67 +/- 41% after 22 h, and 93 +/- 2% after 42 h of fasting. Glycerol's
      conversion to glucose is included in estimates using the enrichment at carbon 5,
      but not carbon 6. Equilibrations with water of the hydrogens bound to carbon 3 of
      pyruvate that become those bound to carbon 6 of glucose and of the hydrogen at
      carbon 2 of glucose produced via glycogenolysis are estimated from the
      enrichments to be approximately 80% complete. Thus, rates of gluconeogenesis can
      be determined without corrections required in other tracer methodologies. After
      an overnight fast gluconeogenesis accounts for approximately 50% and after 42 h
      of fasting for almost all of glucose production in healthy subjects.

PMID- 8755649
TI  - Vascular incorporation of alpha-tocopherol prevents endothelial dysfunction due
      to oxidized LDL by inhibiting protein kinase C stimulation.
AB  - Excess vascular oxidative stress has been linked to impaired endothelium
      dependent arterial relaxation in hypercholesterolemia. alpha-Tocopherol (AT)
      preserves endothelial function in hypercholesterolemia although the mechanism(s)
      for this protective effect is (are) not known. We examined the tissue-specific
      effects of AT on oxidized LDL (ox-LDL)-mediated endothelial dysfunction in male
      New Zealand White rabbits. Animals consumed chow deficient in (< 10 IU/kg) or
      supplemented with (1,000 IU/kg) AT for 28 d. Exposure of thoracic aortae from AT
      deficient animals to ox-LDL (0-500 microg/ml) for 4 h produced dose-dependent
      inhibition of acetylcholine-mediated relaxation (P < 0.05) while vessels derived
      from animals consuming AT were resistant to ox-LDL-mediated endothelial
      dysfunction. Animals consuming AT demonstrated a 100-fold increase in vascular AT
      content and this was strongly correlated with vessel resistance to endothelial
      dysfunction from ox-LDL (R = 0.67; P = 0.0014). These results were not explained
      by an effect of AT on ox-LDL-mediated cytotoxicity by LDH assay or scanning
      electron microscopy. Vascular incorporation of AT did produce resistance to
      endothelial dysfunction from protein kinase C stimulation, an event that has been
      implicated in the vascular response to ox-LDL. Human aortic endothelial cells
      loaded with AT also demonstrated resistance to protein kinase C stimulation by
      both phorbol ester and ox-LDL. Thus, these data indicate that enrichment of
      vascular tissue with AT protects the vascular endothelium from ox-LDL-mediated
      dysfunction, at least in part, through the inhibition of protein kinase C
      stimulation. These findings suggest one potential mechanism for the observed
      beneficial effect of AT in preventing the clinical expression of coronary artery
      disease that is distinct from the antioxidant protection of LDL.

PMID- 8755650
TI  - Studies of renal injury. II. Activation of the glucose transporter 1 (GLUT1) gene
      and glycolysis in LLC-PK1 cells under Ca2+ stress.
AB  - Injury to the renal proximal tubule is common and may be followed by either
      recovery or cell death. The survival of injured cells is supported by a transient
      change in cellular metabolism that maintains life even when oxygen tension is
      reduced. This adaptive process involves the activation of the gene encoding the
      glucose transporter GLUT1, which is essential to maintain the high rates of
      glucose influx demanded by glycolysis. We hypothesized that after cell injury
      increases of cell Ca2+ (Ca2+i) initiate the flow of information that culminates
      with the upregulation of the stress response gene GLUT1. We found that elevations
      of Ca2+i caused by the calcium ionophore A23187 activated the expression of the
      GLUT1 gene in LLC-PK1 cells. The stimulatory effect of Ca2+i on GLUT1 gene
      expression was, at least in part, transcriptional and resulted in higher levels
      of GLUT1 mRNA, cognate protein, cellular hexose transport activity, glucose
      consumption, and lactate production. This response was vital to the renal cells,
      as its interruption severely increased Ca2+-induced cytotoxicity and cell
      mortality. We propose that increases of Ca2+i initiate stress responses,
      represented in part by activation of the GLUT1 gene, and that disruption to the
      flow of information originating from Ca2+-induced stress, or to the coordinated
      expression of the stress response, prevents cell recovery after injury and may be
      an important cause of permanent renal cell injury and cell death.

PMID- 8755651
TI  - Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein
      differentially expressed and regulated in human and rat brain and other tissues.
AB  - The deiodination of thyroid hormones in extrathyroidal tissues plays an important
      role in modulating thyroid hormone action. The type II deiodinase (DII) converts
      thyroxine to the active hormone 3,5,3'-triiodothyronine, and in the rat is
      expressed in the brain, pituitary gland, and brown adipose tissue (BAT).
      Complementary DNAs (cDNAs) for the types I and III deiodinases (DI and DIII,
      respectively) have been isolated and shown to code for selenoproteins. However,
      information concerning the structure of the mammalian DII remains limited, and
      the pattern of its expression in human tissues is undefined. We report herein the
      identification and characterization of rat and human DII cDNAs. Both code for
      selenoproteins and exhibit limited regions of homology with the DI and DIII. In
      the rat pituitary and BAT, DII mRNA levels are altered more than 10-fold by
      changes in the thyroid hormone status of the animal. Northern analysis of RNA
      derived from human tissues reveals expression of DII transcripts in heart,
      skeletal muscle, placenta, fetal brain, and several regions of the adult brain.
      These studies demonstrate that: (a) the rat and human DII are selenoproteins, (b)
      DII expression in the rat is regulated, at least in part, at the pretranslational
      level in some tissues, and (c) DII is likely to be of considerable physiologic
      importance in thyroid hormone economy in the human fetus and adult.

PMID- 8755652
TI  - Chronic blockade of AT2-subtype receptors prevents the effect of angiotensin II
      on the rat vascular structure.
AB  - Angiotensin II (Ang II) is both a vasoactive and a potent growth-promoting factor
      for vascular smooth muscle cells. Little is known about the in vivo contribution
      of AT1 and AT2 receptor activation to the biological action of Ang II. Therefore,
      we investigated the effect of AT1 or AT2 subtype receptor chronic blockade by
      losartan or PD123319 on the vascular hypertrophy in rats with Ang II-induced
      hypertension. Normotensive rats received for 3 wk subcutaneous infusions of Ang
      II (120 ng/kg per min), or Ang II + PD 123319 (30 mg/kg per d), or Ang II +
      losartan (10 mg/kg per d) or PD 123319 alone, and were compared with control
      animals. In normotensive animals, chronic blockade of AT2 receptors did not
      affect the plasma level of angiotensin II and the vascular reactivity to
      angiotensin II mediated by the AT1 receptor. Chronic blockade of AT1I in rats
      receiving Ang II resulted in normal arterial pressure, but it induced significant
      aortic hypertrophy and fibrosis. Chronic blockade of AT2 receptors in Ang II
      induced hypertensive rats had no effect on arterial pressure, but antagonized the
      effect of Ang II on arterial hypertrophy and fibrosis, suggesting that in vivo
      vasotrophic effects of Ang II are at least partially mediated via AT2 subtype
      receptors.

PMID- 8755653
TI  - Suppression of p53 activity and p21WAF1/CIP1 expression by vascular cell integrin
      alphaVbeta3 during angiogenesis.
AB  - Induction of p53 activity in cells undergoing DNA synthesis represents a
      molecular conflict that can lead to apoptosis. During angiogenesis, proliferative
      endothelial cells become apoptotic in response to antagonists of integrin
      alphavbeta3 and this leads to the regression of angiogenic blood vessels, thereby
      blocking the growth of various human tumors. Evidence is presented that
      administration of alphavbeta3 antagonists during angiogenesis in vivo selectively
      caused activation of endothelial cell p53 and increased expression of the p53
      inducible cell cycle inhibitor p21WAF1/CIP1. In vitro studies revealed that the
      ligation state of human endothelial cell alphavbeta3 directly influenced p53
      activity and the bax cell death pathway. Specifically, agonists of endothelial
      cell alphavbeta3, but not other integrins, suppressed p53 activity, blocked
      p21WAF1/CIP1 expression, and increased the bcl-2/bax ratio, thereby promoting
      cell survival. Thus, ligation of vascular cell integrin alphavbeta3 promotes a
      critical and specific adhesion-dependent cell survival signal during angiogenesis
      leading to inhibition of p53 activity, decreased expression of p21WAF1/CIP1, and
      suppression of the bax cell death pathway.

PMID- 8755654
TI  - The role of vascular injury and hemodynamics in rat pulmonary artery remodeling.
AB  - Vascular remodeling in adult human elastic pulmonary arteries is characterized by
      diffuse neointimal lesions containing smooth muscle cells expressing
      extracellular matrix genes. Recent studies suggest vascular injury is needed to
      initiate remodeling and that growth factor mediators participate in the repair
      response. However, because neointimal formation is only observed in patients with
      pulmonary artery blood pressures approaching systemic levels, it has been
      hypothesized that systemic-like hemodynamic conditions are also necessary. To
      test that hypothesis, subclavian-pulmonary artery anastomoses were created in
      Sprague-Dawley rats under three different experimental conditions: no
      accompanying injury, or after monocrotaline or balloon endarterectomy injury.
      Pulmonary vascular remodeling was not induced by the subclavian-pulmonary artery
      anastomosis alone. A non-neointimal pattern of remodeling after mild
      monocrotaline-induced injury was converted into a neointimal pattern in the
      presence of the anastomosis. Neointima was also observed after severe, balloon
      endarterectomy-induced injury even in the absence of anastomosis. Tropoelastin,
      type I procollagen and TGF-beta gene expression, and angiotensin converting
      enzyme immunoreactivity, was confined to the neointima resembling the pattern of
      gene expression and immunoreactivity in human hypertensive elastic pulmonary
      artery neointimal lesions. These observations introduce the concepts that the
      type of injury and the associated hemodynamic conditions can modify the elastic
      pulmonary artery response to injury.

PMID- 8755655
TI  - Sequence-independent inhibition of in vitro vascular smooth muscle cell
      proliferation, migration, and in vivo neointimal formation by phosphorothioate
      oligodeoxynucleotides.
AB  - Phosphorothioate oligodeoxynucleotides (PS oligos) are antisense (sequence
      specific) inhibitors of vascular smooth muscle cell (SMC) proliferation when
      targeted against different genes. Recently an aptameric G-quartet inhibitory
      effect of PS oligos has been demonstrated. To determine whether PS oligos
      manifest non-G-quartet, non-sequence-specific effects on human aortic SMC, we
      examined the effects of S-dC28, a 28-mer phosphorothioate cytidine homopolymer,
      on SMC proliferation induced by several SMC mitogens. S-dC28 significantly
      inhibited SMC proliferation induced by 10% FBS as well as the mitogens PDGF,
      bFGF, and EGF without cytotoxicity. Moreover, S-dC28 abrogated PDGF-induced in
      vitro migration in a modified micro-Boyden chamber. Furthermore, S-dC28
      manifested in vivo antiproliferative effects in the rat carotid balloon injury
      model. S-dC28 suppressed neointimal cross-sectional area by 73% and the
      intima/media area ratio by 59%. Therefore, PS oligos exert potent non-G-quartet,
      non-sequence-specific effects on in vitro SMC proliferation and migration as well
      as in vivo neointimal formation.

PMID- 8755656
TI  - The PAX2 tanscription factor is expressed in cystic and hyperproliferative
      dysplastic epithelia in human kidney malformations.
AB  - Human dysplastic kidneys are developmental aberrations which are responsible for
      many of the very young children with chronic renal failure. They contain poorly
      differentiated metanephric cells in addition to metaplastic elements. We recently
      demonstrated that apoptosis was prominent in undifferentiated cells around
      dysplastic tubules (Winyard, P.J.D., J. Nauta, D.S. Lirenman, P. Hardman, V.R.
      Sams, R.A. Risdon, and A.S. Woolf. 1996. Kidney Int. 49:135-146), perhaps
      explaining the tendency of some of these organs to regress. In contrast,
      apoptosis was rare in dysplastic epithelia which are thought to be ureteric bud
      malformations. On occasion, these tubules form cysts which distend the abdominal
      cavity (the multicystic dysplastic kidney) and dysplastic kidneys may rarely
      become malignant. We now demonstrate that dysplastic tubules maintain a high rate
      of proliferation postnatally and that PAX2, a potentially oncogenic transcription
      factor, is expressed in these epithelia. In contrast, both cell proliferation and
      PAX2 are downregulated during normal maturation of human collecting ducts. We
      demonstrate that BCL2, a protein which prevents apoptosis in renal mesenchymal to
      epithelia] conversion, is expressed ectopically in dysplastic kidney epithelia.
      We propose that dysplastic cyst formation may be understood in terms of aberrant
      temporal and spatial expression of master genes which are tightly regulated in
      the normal program of human nephrogenesis.

PMID- 8755657
TI  - Role of Ca2+ in the action of adrenocorticotropin in cultured human adrenal
      glomerulosa cells.
AB  - The present report details the role of Ca2+ in the early events of ACTH action in
      human adrenal glomerulosa cells. Threshold stimulations of both aldosterone and
      cAMP production were obtained with a concentration of 10 pM ACTH, an ED50 of 0.1
      nM, and maximal aldosterone stimulation (5.5-fold increase over control) at 10 nM
      ACTH. ACTH also induced a sustained increase of intracellular calcium ([Ca2+]i)
      with maximal stimulation of 1.6 +/- 0.1-fold over control values. This increase
      does not involve mobilization of calcium from intracellular pools since no
      response was observed in Ca2+-free medium or in the presence of nifedipine,
      suggesting the involvement of Ca2+ influx by L-type Ca2+ channels. This was
      confirmed by patch clamp studies that demonstrated that ACTH stimulates L-type
      Ca2+ channels. Moreover, the Ca2+ ion is not required for ACTH binding to its
      receptor, but is essential for sustained cAMP production and aldosterone
      secretion after ACTH stimulation. These results indicate that, in human adrenal
      glomerulosa cells, a positive feedback loop between adenylyl cyclase-protein
      kinase A-Ca2+ channels ensures a slow but sustained [Ca2+]i increase that is
      responsible for sustained cAMP production and aldosterone secretion.

PMID- 8755658
TI  - Regulation of human heart contractility by essential myosin light chain isoforms.
AB  - Most of the patients with congenital heart diseases express the atrial myosin
      light chain 1 (ALC-1) in the right ventricle. We investigated the functional
      consequences of ALC-1 expression on the myosin cycling kinetics in the intact
      sarcomeric structure using multicellular demembranated fibers ("skinned fibers")
      from the right ventricular infundibulum of patients with Tetralogy of Fallot
      (TOF), double outlet right ventricle (DORV), and infundibular pulmonary stenosis
      (IPS), Force-velocity relation was analyzed by the constant-load technique at
      maximal Ca2+ activation (pCa 4.5). Half-time of tension development (t1/2) was
      investigated by monitoring contraction initiation upon photolytic release of ATP
      from caged-ATP in rigor. The patients investigated here expressed between 0 and
      27% ALC-1. There was a statistically significant correlation between ALC-l and
      maximal shortening velocity (Vmax) which rose 1.87-fold from 1.2 muscle length
      per second (ML/s) to 2.25 ML/s in a normal (0% ALC-1) and diseased (19.9% ALC-1)
      ventricle. Half-time of tension development decreased 1.85-fold with increasing
      ALC-1 expression (t1/2) was 0.252 s and 0.136 s at 2 and 18.4% ALC-1,
      respectively). We conclude that the expression of ALC-1 in the human heart
      modulates cross-bridge cycling kinetics accelerating shortening velocity and
      isometric tension production.

PMID- 8755659
TI  - Transcriptional activation of RACTK1 K+ channel gene by apical alkalization in
      renal cortical collecting duct cells.
AB  - We have previously demonstrated that RACTK1 cDNA encodes a pH sensitive K+
      channel expressed in the apical side of renal collecting tubule cells. To
      determine whether extracellular pH induces the RACTK1 gene expression in the
      renal cortical collecting duct (CCD) cells, we measured mRNA of the RACTK1 using
      cultured rabbit CCD cells. Alkalization of incubation medium activated the
      transcription of the RACKTK1 gene in a time- and dose-dependent manner after 1 h,
      and reached a maximal level after 12 h. To examine whether the stimulation of
      mRNA by alkalization of body fluid occurs also in vivo, mRNA levels were measured
      in mice loaded with acid or alkali. The RACTK1 mRNA was increased in association
      with the rise in urinary pH. To examine side face of the effect of pH on
      stimulation of mRNA, we observed the effect of pH in the apical or the
      basolateral side in the preparation where CCD cells were cultured on filter
      membrane supports. Alkalization of the apical side but not of the basolateral
      side, was shown to be a determinant in inducting the RACTK1 mRNA. These findings
      suggest that, in addition to rapid direct regulation of RACTK1 K+ channel
      conductance by intracellular pH, this channel is also regulated by the changes in
      luminal pH through synthesis of channel protein by transcriptional activation.

PMID- 8755660
TI  - Vascular endothelial growth factor is produced by peritoneal fluid macrophages in
      endometriosis and is regulated by ovarian steroids.
AB  - Angiogenesis is important in the pathophysiology of endometriosis, a condition
      characterized by implantation of ectopic endometrium in the peritoneal cavity.
      Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved
      in physiological and pathological angiogenesis, and elevated levels of VEGF are
      found in peritoneal fluid of patients with endometriosis. Our aim was to
      investigate the site of expression and regulation of VEGF in endometriosis. VEGF
      immunoreactivity was found in tissue macrophages present in ectopic endometrium
      and in activated peritoneal fluid macrophages. Macrophage activation was highest
      in women with endometriosis, and media conditioned by peritoneal fluid
      macrophages from these women caused a VEGF-dependent increase in endothelial cell
      proliferation above that seen from normal women. Peritoneal fluid macrophages
      secreted VEGF in response to ovarian steroids, and this secretion was enhanced
      after activation with lipopolysaccharide. Peritoneal fluid macrophages expressed
      receptors for steroid hormones. VEGF receptors flt and KDR (kinase domain
      receptor) were also detected, suggesting autocrine regulation. During the
      menstrual cycle, expression of flt was constant but that of KDR was increased in
      the luteal phase, at which time the cells migrated in response to VEGF. KDR
      expression and the migratory response were significantly higher in patients with
      endometriosis. This study demonstrates that activated macrophages are a major
      source of VEGF in endometriosis and that this expression is regulated directly by
      ovarian steroids.

PMID- 8755661
TI  - Downregulation of vascular endothelial growth factor receptors by tumor necrosis
      factor-alpha in cultured human vascular endothelial cells.
AB  - Vascular endothelial growth factor (VEGF) potently stimulates angiogenesis,
      whereas TNF-alpha has both pro- and anti-angiogenic activity. By measuring
      thymidine uptake, we found that TNF-alpha blocked a 2.3-fold increase in DNA
      synthesis induced by VEGF in human endothelial cells. To explore the possibility
      that the two interact to regulate endothelial cell proliferation, we examined the
      effect of TNF-alpha on VEGF receptor expression. In venous and arterial
      endothelial cells, TNF-alpha potently reduced mRNA transcripts of the two VEGF
      receptors (KDR/flk-1 and flt-1) in a dose- and time-dependent fashion. TNF-alpha
      at 1 ng/ml induced maximal inhibition of mRNA expression, which fell by
      approximately 70% after 24 h. TNF-alpha treatment did not significantly affect
      the KDR/flk-1 half-life but did decrease its rate of transcription to 40% of
      control. The decrease in KDR/flk-1 mRNA depended partially on new protein
      synthesis and was abolished by phorbol ester pretreatment. TNF-alpha decreased
      the amount of 35S-labeled KDR/flk-1 immunoprecipitated by an antibody specific
      for KDR/flk-1 to 18% of control. We conclude that TNF-alpha downregulates
      expression of both VEGF receptors in human endothelial cells and that this effect
      is transcriptional (at least for KDR/flk-1). These data support the hypothesis
      that TNF-alpha exerts its antiangiogenic effect in part by modulating the VEGF
      specific angiogenic pathway.

PMID- 8755662
TI  - Arylsulfatase B activities and glycosaminoglycan levels in retrovirally
      transduced mucopolysaccharidosis type VI cells. Prospects for gene therapy.
AB  - Mucopolysacchariodosis type VI (MPS VI) is the lysosomal storage disorder caused
      by the deficient activity of arylsulfatase B (ASB; N-acetylgalactosamine 4
      sulfatase) and the subsequent accumulation of the glycosaminoglycan (GAG),
      dermatan sulfate. In this study, a retroviral vector containing the full-length
      human ASB cDNA was constructed and used to transduce skin fibroblasts,
      chondrocytes, and bone marrow cells from human patients, cats, or rats with MPS
      VI. The ASB vector expressed high levels of enzymatic activity in each of the
      cell types tested and, in the case of cat and rat cells, enzymatic expression led
      to complete normalization of 35SO4 incorporation. In contrast, overexpression of
      ASB in human MPS VI skin fibroblasts did not lead to metabolic correction. High
      level ASB expression was detected for up to eight weeks in transduced MPS VI cat
      and rat bone marrow cultures, and PCR analysis demonstrated retroviral-mediated
      gene transfer to approximately 30-50% of the CFU GM-derived colonies. Notably,
      overexpression of ASB in bone marrow cells led to release of the enzyme into the
      media and uptake by MPS VI cat and rat skin fibroblasts and/or chondrocytes via
      the mannose-6-phosphate receptor system, leading to metabolic correction. Thus,
      these studies provide important rationale for the development of gene therapy for
      this disorder and lay the frame-work for future in vivo studies in the animal
      model systems.

PMID- 8755663
TI  - Requirement and role of C5a in acute lung inflammatory injury in rats.
AB  - The complement activation product, C5a, may play a key role in the acute
      inflammatory response. Polyclonal antibody to rat C5a was used to define the
      requirements for C5a in neutrophil-dependent inflammatory lung injury after
      systemic activation of complement by cobra venom factor (CVF) or after
      intrapulmonary deposition of IgG immune complexes. In the CVF model, intravenous
      infusion (but not intratracheal instillation) of anti-C5a produced a dose
      dependent reduction in lung permeability and in lung content of myeloperoxidase.
      In C6-deficient rats, CVF infusion caused the same level of lung injury (measured
      by leak of 125I-albumin) as found in C6-sufficient rats. In the IgG immune
      complex model of lung injury, anti-C5a administered intratracheally (but not
      intravenously) reduced in a dose-dependent manner both the increase in lung
      vascular permeability as well as the buildup of lung myeloperoxidase. Treatment
      with anti-C5a greatly suppressed upregulation of lung vascular intercellular
      adhesion molecule-1 (ICAM-1). This was correlated with a substantial drop in
      levels of TNFalpha in bronchoalveolar fluids. These data demonstrate the
      requirement for C5a in the two models of injury. In the IgG immune complex model,
      C5a is required for the full production of TNFalpha and the corresponding
      upregulation of lung vascular ICAM-1.

PMID- 8755664
TI  - Activation of endogenous deltaF508 cystic fibrosis transmembrane conductance
      regulator by phosphodiesterase inhibition.
AB  - Many heterologously expressed mutants of the cystic fibrosis transmembrane
      conductance regulator (CFTR) exhibit residual chloride channel activity that can
      be stimulated by agonists of the adenylate cyclase/protein kinase A pathway.
      Because of clinical implications for cystic fibrosis of activating mutants in
      vivo, we are investigating whether deltaF508, the most common disease-associated
      CFTR mutation, can be activated in airway epithelial cells. We have found that,
      36Cl- efflux can be stimulated 19-61% above baseline by beta-adrenoreceptor
      agonists and cGI-phosphodiesterase inhibitors in transformed nasal polyp (CF-T43)
      cells homozygous for the deltaF508 mutation. The increase in 36Cl- permeability
      is diminished by protein kinase A inhibitors and is not mediated by an increase
      in intracellular calcium concentrations. Preincubation of CF-T43 cells with CFTR
      anti-sense oligonucleotides prevented an increase in 36Cl- efflux in response to
      beta-agonist and phosphodiesterase inhibitor. Primary cells isolated from CF
      nasal polyps gave similar results. These data indicate that endogenous levels of
      deltaF508 protein can be stimulated to increase 36Cl- permeability in airway
      epithelial cells.

PMID- 8755665
TI  - Bcr/Abl expression stimulates integrin function in hematopoietic cell lines.
AB  - Cell adhesion to the extracellular matrix is largely mediated by adhesion
      molecules of the integrin family and is often diminished upon oncogenic
      transformation. However, we show here that the chronic myelogenous leukemia
      oncogene Bcr/Abl has positive effects on VLA-4 and VLA-5 integrin function. The
      presence of Bcr/Abl in the GM-CSF- or IL-3-dependent hematopoietic cell lines
      MO7e, 32D, and BaF/3 enhanced cell binding to both soluble and immobilized
      fibronectin. The effect was due to enhanced function of the VLA-5 integrin
      fibronectin receptor and not to increased surface expression. In parallel,
      Bcr/Abl stimulated cell adhesion to the VLA-4 integrin ligand VCAM-1. Stimulation
      of VLA-5 function directly correlated with induction of Bcr/Abl tyrosine kinase
      activity in a temperature-sensitive kinase mutant. Thus, Bcr/Abl stimulates
      integrin-dependent cell adhesion, by a mechanism involving increased ligand
      binding, with the tyrosine kinase activity of Bcr/Abl likely playing a key role.
      Consistent with these results, hematopoietic precursor cells from chronic
      myelogenous leukemia patients also showed increased adhesion to fibronectin.

PMID- 8755666
TI  - Neutrophil infiltration, glial reaction, and neurological disease in transgenic
      mice expressing the chemokine N51/KC in oligodendrocytes.
AB  - Chemokines (pro-inflammatory chemoattractant cytokines) are expressed in
      pathological conditions of the central nervous system (CNS). Previous studies
      suggested that the CNS is relatively resistant to leukocyte diapedesis after
      chemokine injection, leaving their functional role unresolved. The CNS function
      of N51/KC, a neutrophil-selective chemokine, was addressed by expressing N51/KC
      under control of the myelin basic protein (MBP) promoter in transgenic (tg) mice
      (MBP-N51/KC mice). CNS-specific N51/KC expression produced remarkable neutrophil
      infiltration into perivascular, meningeal, and parenchymal sites, demonstrating
      that this chemokine exerts the multiple functions in vivo required to recruit
      leukocytes into the CNS. MBP-N5 1/KC mice represent an incisive model for the
      molecular dissection of neutrophil entry into the CNS. Unexpectedly, MBP-N51/KC
      mice developed a neurological syndrome of pronounced postural instability and
      rigidity at high frequency beginning at 40 days of age, well after peak chemokine
      expression. 68/182 mice in one tg fine were found dead before one year of age,
      with prominent neurological symptoms premortem in 26 (38%). Florid microglial
      activation and blood-brain barrier disruption without dysmyelination were the
      major neuropathological alterations. Late-onset neurological symptoms in MBP
      N51/KC mice may indicate unanticipated consequences of CNS chemokine expression.

PMID- 8755667
TI  - Glucose- and GTP-dependent stimulation of the carboxyl methylation of CDC42 in
      rodent and human pancreatic islets and pure beta cells. Evidence for an essential
      role of GTP-binding proteins in nutrient-induced insulin secretion.
AB  - Several GTP-binding proteins (G-proteins) undergo post-translational
      modifications (isoprenylation and carboxyl methylation) in pancreatic beta cells.
      Herein, two of these were identified as CDC42 and rap 1, using Western blotting
      and immunoprecipitation. Confocal microscopic data indicated that CDC42 is
      localized only in islet endocrine cells but not in acinar cells of the pancreas.
      CDC42 undergoes a guanine nucleotide-specific membrane association and carboxyl
      methylation in normal rat islets, human islets, and pure beta (HIT or INS-1)
      cells. GTPgammaS-dependent carboxyl methylation of a 23-kD protein was also
      demonstrable in secretory granule fractions from normal islets or beta cells. AFC
      (a specific inhibitor of prenyl-cysteine carboxyl methyl transferases) blocked
      the carboxyl methylation of CDC42 in five types of insulin-secreting cells,
      without blocking GTPgammaS-induced translocation, implying that methylation is a
      consequence (not a cause) of transfer to membrane sites. High glucose (but not a
      depolarizing concentration of K+) induced the carboxyl methylation of CDC42 in
      intact cells, as assessed after specific immunoprecipitation. This effect was
      abrogated by GTP depletion using mycophenolic acid and was restored upon GTP
      repletion by coprovision of guanosine. In contrast, although rap 1 was also
      carboxyl methylated, it was not translocated to the particulate fraction by
      GTPgammaS; furthermore, its methylation was also stimulated by 40 mM K+
      (suggesting a role which is not specific to nutrient stimulation). AFC also
      impeded nutrient-induced (but not K+-induced) insulin secretion from islets and
      beta cells under static or perifusion conditions, whereas an inactive structural
      analogue of AFC failed to inhibit insulin release. These effects were reproduced
      not only by S-adenosylhomocysteine (another methylation inhibitor), but also by
      GTP depletion. Thus, the glucose- and GTP-dependent carboxyl methylation of G
      proteins such as CDC42 is an obligate step in the stimulus-secretion coupling of
      nutrient-induced insulin secretion, but not in the exocytotic event itself.
      Furthermore, AFC blocked glucose-activated phosphoinositide turnover, which may
      provide a partial biochemical explanation for its effect on secretion, and
      implies that certain G-proteins must be carboxyl methylated for their interaction
      with signaling effector molecules, a step which can be regulated by intracellular
      availability of GTP.

PMID- 8755668
TI  - Functional beta3-adrenoceptor in the human heart.
AB  - Beta3-adrenoceptors are involved in metabolism, gut relaxation, and vascular
      vasodilation. However, their existence and role in the human heart have not been
      documented. We investigated the effects of several beta-adrenoceptor agonists and
      antagonists on the mechanical properties of ventricular endomyocardial biopsies.
      In the presence of nadolol, a beta1- and beta2-adrenoceptor antagonist,
      isoprenaline produced consistent negative inotropic effects. Similar negative
      inotropic effects also resulted from the action of beta3-adrenoceptor agonists
      with an order of potency: BRL 37344 > SR 58611 approximately CL 316243 > CGP
      12177. The dose-response curve to BRL 37344-decreasing myocardial contractility
      was not modified by pretreatment with nadolol, but was shifted to the right by
      bupranolol, a nonselective beta-adrenoceptor antagonist. Beta3-adrenoceptor
      agonists also induced a reduction in the amplitude and an acceleration in the
      repolarization phase of the human action potential. Beta3-adrenoceptor
      transcripts were detected in human ventricle by a polymerase chain reaction
      assay. These results indicate that: (a) beta3-adrenoceptors are present and
      functional in the human heart; and (b) these receptors are responsible for the
      unexpected negative inotropic effects of catecholamines and may be involved in
      pathophysiological mechanisms leading to heart failure.

PMID- 8755669
TI  - Preferential influx and decreased fractional loss of lipoprotein(a) in
      atherosclerotic compared with nonlesioned rabbit aorta.
AB  - The aim was to investigate the atherogenic potential of lipoprotein(a) (Lp(a))
      and to further our understanding of the atherogenic process by measuring rates of
      transfer into the intima-inner media (i.e., intimal clearance) and rates of loss
      from the intima-inner media (i.e., fractional loss) of Lp(a) and LDL using
      cholesterol-fed rabbits with nonlesioned (n = 13) or atherosclerotic aortas (n =
      12). In each rabbit, 131I-Lp(a) (or 131I-LDL) was injected intravenously 26 h
      before and 125I-Lp(a) (or 125I-LDL) 3 h before the aorta was removed and divided
      into six consecutive segments of similar size. The intimal clearance of Lp(a) and
      LDL was similar and markedly increased in atherosclerotic compared with
      nonlesioned aortas (ANOVA, effect of atherosclerosis: P < 0.0001). Fractional
      losses of labeled Lp(a) and labeled LDL in atherosclerotic aorta were on average
      25 and 43%, respectively, of that in nonlesioned aortas (ANOVA, effect of
      atherosclerosis: P < 0.0001). Fractional loss of Lp(a) was 73% of that of LDL
      (ANOVA, effect of type of lipoprotein: P = 0.07). These data suggest that the
      development of atherosclerosis is associated with increased influx as well as
      decreased fractional loss of Lp(a) and LDL from the intima. Accordingly, Lp(a)
      may share with LDL the potential for causing atherosclerosis.

PMID- 8755670
TI  - Infection of human intestinal epithelial cells with invasive bacteria upregulates
      apical intercellular adhesion molecule-1 (ICAM)-1) expression and neutrophil
      adhesion.
AB  - The acute host response to gastrointestinal infection with invasive bacteria is
      characterized by an accumulation of neutrophils in the lamina propria, and
      neutrophil transmigration to the luminal side of the crypts. Intestinal
      epithelial cells play an important role in the recruitment of inflammatory cells
      to the site of infection through the secretion of chemokines. However, little is
      known regarding the expression, by epithelial cells, of molecules that are
      involved in interactions between the epithelium and neutrophils following
      bacterial invasion. We report herein that expression of ICAM-1 on human colon
      epithelial cell lines, and on human enterocytes in an in vivo model system, is
      upregulated following infection with invasive bacteria. Increased ICAM-1
      expression in the early period (4-9 h) after infection appeared to result mainly
      from a direct interaction between invaded bacteria and host epithelial cells
      since it co-localized to cells invaded by bacteria, and the release of soluble
      factors by epithelial cells played only a minor role in mediating increased ICAM
      1 expression. Furthermore, ICAM-1 was expressed on the apical side of polarized
      intestinal epithelial cells, and increased expression was accompanied by
      increased neutrophil adhesion to these cells. ICAM-1 expression by intestinal
      epithelial cells following infection with invasive bacteria may function to
      maintain neutrophils that have transmigrated through the epithelium in close
      contact with the intestinal epithelium, thereby reducing further invasion of the
      mucosa by invading pathogens.

PMID- 8755672
TI  - Infectious intestinal disease in elderly people.
AB  - This paper analyses routinely available data on infectious intestinal diseases
      occurring in people aged 65 years and over in England and Wales from 1990 to
      1994. These data include annual reports of consultations with general
      practitioners in spotter practices collated by the Royal College of General
      Practitioners, notifications of food poisoning collated by the Office of
      Population Censuses and Surveys, hospital admissions extracted from Hospital
      Episode Statistics data, reports of general outbreaks and laboratory reports of
      faecal isolates both collated by the PHLS Communicable Disease Surveillance
      Centre, and death registrations held at the Office of Population Censuses and
      Surveys. From 1 January 1990 to 31 December 1994 a total of 8,910 episodes of
      infectious intestinal disease in people aged 65 years and over were seen in the
      93 spotter practices that care for a population of all ages of about 700,000.
      This extrapolates to about 925,000 cases in elderly people in England and Wales,
      if consultation rates in spotter practices are representative. Twenty-seven
      thousand two hundred and thirty-three cases of food poisoning were notified and
      46,216 faecal isolates were reported in people of the same age group. The
      commonest pathogens detected were campylobacter, Clostridium difficile and
      salmonellas. Thirteen thousand five hundred and eighty-five people aged 65 years
      and over were admitted to hospital with infectious intestinal disease between 1
      April 1991 and 31 March 1994. The PHLS Communicable Disease Surveillance Centre
      learnt of 360 outbreaks in residential institutions and hospital wards for
      elderly people between 1 January 1992 and 31 December 1994, 52% of which were
      caused by small round structured viruses. Seven hundred and seventy-seven deaths
      attributable to infectious intestinal disease in elderly people were registered
      from 1990 to 1994. Infectious intestinal disease is a largely preventable group
      of conditions that cause substantial morbidity and mortality in elderly people.
      Appropriate food hygiene and infection control measures, particularly in
      institutions, will help to reduce the incidence of infectious intestinal disease
      in elderly people.

PMID- 8755673
TI  - Four outbreaks of Salmonella enteritidis phage type 4 food poisoning linked to a
      single baker.
AB  - An outbreak of gastrointestinal illness occurred among a party of diners at a
      hotel in South Yorkshire. A case control study identified a gateau, from an
      outside supplier, as the likeliest vehicle of infection. Further gateaux from the
      same baker's premises and other outlets were examined microbiologically. Three
      other outbreaks of food poisoning in neighbouring districts were recognised and
      found to be associated with gateaux supplied by the same baker. A total of 32
      cases were identified. Stool specimens from 24 cases grew Salmonella enteritidis
      phage type (PT) 4. The same organism was also grown from gateau in the domestic
      refrigerator of the chef of one hotel, cheesecake made by the same baker, and a
      gateau and ingredients from the baker's premises. The isolates of S. enteritidis
      PT4 were all fully sensitive to antibiotics, and had the same plasmid and pulsed
      field gel electrophoresis profiles. It is most likely that cross contamination
      occurred from infected raw eggs on the baker's premises. The control measures
      instituted probably prevented two further outbreaks, and the baker now uses only
      pasteurised eggs. The benefits of close cooperation between different local and
      health authority districts in the investigation of the outbreaks are discussed.

PMID- 8755671
TI  - Differential sympathetic neural control of oxygenation in resting and exercising
      human skeletal muscle.
AB  - Metabolic products of skeletal muscle contraction activate metaboreceptor muscle
      afferents that reflexively increase sympathetic nerve activity (SNA) targeted to
      both resting and exercising skeletal muscle. To determine effects of the
      increased sympathetic vasoconstrictor drive on muscle oxygenation, we measured
      changes in tissue oxygen stores and mitochondrial cytochrome a,a3 redox state in
      rhythmically contracting human forearm muscles with near infrared spectroscopy
      while simultaneously measuring muscle SNA with microelectrodes. The major new
      finding is that the ability of reflex-sympathetic activation to decrease muscle
      oxygenation is abolished when the muscle is exercised at an intensity > 10% of
      maximal voluntary contraction (MVC). During high intensity handgrip, (45% MVC),
      contraction-induced decreases in muscle oxygenation remained stable despite
      progressive metaboreceptor-mediated reflex increases in SNA. During mild to
      moderate handgrips (20-33% MVC) that do not evoke reflex-sympathetic activation,
      experimentally induced increases in muscle SNA had no effect on oxygenation in
      exercising muscles but produced robust decreases in oxygenation in resting
      muscles. The latter decreases were evident even during maximal metabolic
      vasodilation accompanying reactive hyperemia. We conclude that in humans
      sympathetic neural control of skeletal muscle oxygenation is sensitive to
      modulation by metabolic events in the contracting muscles. These events are
      different from those involved in either metaboreceptor muscle afferent activation
      or reactive hyperemia.

PMID- 8755674
TI  - Outbreak of Escherichia coli O157 phage type 2 infection associated with eating
      precooked meats.
AB  - Fourteen cases of Escherichia coli O157 infection were reported to the consultant
      in communicable disease control in Sunderland Health Authority in August 1995. E.
      coli O157 phage type 2, Vero cytotoxin 2 was isolated from the faeces of ten
      cases. Nine of the isolates were indistinguishable by Vero cytotoxin subtyping
      and analysis of chromosomal DNA. Two cases with haemolytic uraemic syndrome were
      confirmed serologically and two cases remained unconfirmed. A case control study
      showed infection with E. coli O157 to be associated with having eaten precooked
      meats from a single shop. Environmental investigations at the shop showed that
      cooked meats were stored close to raw beef, raw meats were left on preparation
      surfaces, and the same staff served both raw and cooked meats. This outbreak
      draws attention to standards of food preparation and handling in outbreaks of E.
      coli O157, the issue of cross contamination, and the need to improve local
      surveillance of haemolytic uraemic syndrome.

PMID- 8755675
TI  - [Abrogation of leprosy prevention law and public health].

PMID- 8755676
TI  - [Factors affecting ADL improvement and QOL in stroke patients a community-based
      study].
AB  - To clarify the factors affecting improvement of activities of daily living (ADL)
      and quality of life (QOL) in stroke patients, 141 patients and their families
      attending municipal rehabilitation programs in Saitama Prefecture were surveyed
      by means of self-rating questionnaires and interviews. Subjects had attended the
      rehabilitation programs for 0-16 (mean 3.2) years. The patients were divided into
      two groups, i.e., ADL-improved and ADL-unimproved, according to Katz scale scores
      before and after their rehabilitation. Results of the multiple logistic
      regression analysis indicated that initial ADL before attending the
      rehabilitation programs and a short time interval between disease onset and start
      of rehabilitation are major factors for the improvement of ADL. Similarly, old
      age, high ADL, official certification of disability, and low frequency of
      rehabilitation were significant factors for high QOL as measured by Philadelphia
      Geriatric Center morale scale (stepwise multiple regression analysis). It is
      suggested that municipal rehabilitation programs pay special attention not only
      to accessibility of low-ADL patients, but also to psychological factors of young
      patients with low ADL, high frequency of attendance at rehabilitation programs
      and no official certification of disability.

PMID- 8755677
TI  - [The short-term effect of a smoking prevention program for the upper graders of
      elementary schools--the results of intervention study for two years with quasi
      experimental design].
AB  - The purpose of this study was to evaluate the short-term effect of a smoking
      prevention program for Japanese elementary school-children in the fifth and sixth
      grades. The program was developed with concepts found in the Know Your Body
      Program and the conclusions of a National Cancer Institute-convened Expert
      Advisory Panel, and focused on teaching about the short-term effects of smoking
      and on resistance to social pressures to smoke. The study was conducted with a
      quasi-experimental design. An intervention group (52 boys and 54 girls) received
      three sessions for both the fifth grade in 1992 and the sixth grade in 1993.
      Moreover, the intervention group received a pre-test before the first session and
      a post-test after the third session in each grade. A comparison group (102 boys
      and 91 girls) received the same tests at the same time as the intervention group,
      but did not receive any program on smoking prevention. The short-term effect of
      the program were evaluated using the results of the pre-test in the fifth grade
      and of the post-test in the sixth grade in both groups. The results were as
      follows: 1) Remarkable short-term effects of the intervention were seen in
      respect to awareness of the importance of not smoking in girls, and also in the
      knowledge of the short-term effects of smoking in both sexes. 2) The intervention
      was not effective with respect to intention to smoke at the age of 20 and self
      efficacy of refusing to smoke in both sexes. 3) The short-term effects were not
      clear in the smoking behavior in both sexes because the rates of ever smokers and
      of monthly smokers were almost the same for two years between the intervention
      group and the comparison group. 4) The smoking behaviors of children, their
      parents and their best friends had little influence on the results of the post
      test in the sixth grade.

PMID- 8755678
TI  - [Risk factors in serologically diagnosed echinococcosis--a case control study in
      the Nemuro region of Hokkaido Prefecture].
AB  - To determine the risk factors for echinococcus infection, we conducted a case
      control study in the Nemuro region of Hokkaido Prefecture. The cases included
      both clinically diagnosed patients with echinococcosis and registered persons who
      were seropositive. The control group was matched by residence, age (+/- 5 years)
      and sex. The data on the 99 cases and 430 controls were collected by mailed
      questionnaire. Because of the long latency of echinococcosis, we investigated the
      potential risk factors over two different periods-from 11-20 years before the
      time of registration, and from 10 years before the registration to the time of
      registration. For the 11-20 years before registration period, using well water as
      drinking water and cattle raising significantly increased the risk of
      echinococcosis. In the period 10 years before registration to the time of
      registration, hog raising also increased the risk. In contrast, drinking tap
      water decreased the risk. These results suggest the importance of a screening
      program, especially targeting people engaged in dairy farming and hog raising, as
      well as the need for extension of tap water services and health education on
      refuse disposal.

PMID- 8755679
TI  - [Effects of lactation and lifestyles including food intake on bone density of
      lactating women].
AB  - Ultrasonic bone densities were measured in 131 lactating women, aged 21 to 42
      years, at 6-590 days postpartum. STIFFNESS Calculated from the combined value of
      speed of sound and broadband ultrasound attenuation at the calcaneus was used as
      an index of bone density. The relationships of STIFFNESS with period of
      lactation, current and past consumption of cow's milk, various food intake
      frequency, history of participating in sports, daily physical activity, using
      calcium drugs and sun exposure were examined using stepwise multiple regression
      analysis, including age and weight as independent variables. 1) The mean (SD) of
      STIFFNESS was 79.8 (11.9). Thirty-three women (25% of subjects) showed STIFFNESS
      less than 70. 2) Period of lactation showed a significant negative effect on
      STIFFNESS (p < 0.05). However, no such effect appeared for women with cow's milk
      intake of less than 100 ml per day. This result suggests a protection of calcium
      levels in bone. 3) Current daily cow's milk intake showed significant positive
      effect on STIFFNESS (p < 0.05). For women lactating less than 150 days, this
      relation between cow's milk intake and STIFFNESS was clear (r = 0.44, p < 0.01).
      4) Significant relation between STIFFNESS and food intake frequencies was found
      in milk and milk products only among various foods. This result indicates that
      cow's milk and milk products are important sources of calcium during lactation.

PMID- 8755680
TI  - [A cohort study on the relationship between lifestyles and total mortality].
AB  - To clarify the relationship between lifestyles and total mortality, a 6-year
      cohort study was conducted for three communities in Wakayama Prefecture. During
      1988-1990, information on lifestyles were obtained from a self-administered
      questionnaire utilizing 125 items. The survey protocol included a concentrated
      effort to train all observers for standardization and quality control. For the
      baseline survey, a total of 4,238 residents (1,947 men and 2,291 women) aged 40
      to 79 years old were recruited from resident registration lists. Of these, 3,048
      participants (1,308 men and 1,740 women) formed the cohort (response rate: 72%).
      Death certificates and change of residence registrations were analyzed annually
      utilizing local public health center and town records. Relative risk (RR) for
      each lifestyle component against total mortality was calculated applying Mantel
      Haenszel methods to adjust for age, past history, walking, smoking (male) and BMI
      (female). During 6 years, 171 deaths (106 men and 65 women) and 63 resident
      changes (20 men and 43 women) were observed. Statistical significant RRs were
      observed for walking (RR: 1.7; p < 0.01) in men, walking (RR: 1.9; p < 0.01) in
      women, BMI (RR: 2.1; p < 0.001) in women, when calculated with all deaths during
      6 years. As of smoking for men, RR was 1,4 (not significant), but by considering
      the possibility of effects of a latent period, and excluding deaths occurring in
      1989 and 1990, RR became 2.1 (p < 0.01). These results suggest that non-smoking,
      walking daily and maintaining a moderate BMI may lower total mortality in this
      population.

PMID- 8755681
TI  - [AIDS seminar for personnel managers in japanese companies--application of health
      belief model and health norm model].

PMID- 8755682
TI  - [Current status of the use of Welfare Centers Japan by foreign children and
      pregnant women living in Japan].
AB  - This survey was conducted to determine how Welfare Centers throughout Japan were
      addressing the health care and welfare issues of foreign children and pregnant
      women living in Japan, and to analyze statistics (1988-1992) on the number of
      consultations by foreigners living in Japan. Questionnaires were mailed to 1220
      Welfare Centers throughout Japan in mid August 1993, and responses from 562
      centers were received. The survey conducted among these centers revealed the
      following information: 1) About half of the Welfare Centers responding had had
      consultations with foreign children and pregnant women, and about 60% of them had
      encountered difficulties, including language problems. 2) Comparison of rural and
      urban areas revealed that a higher percentage of Welfare Centers in the urban
      areas had had foreigners as clients. Welfare Centers were more likely to be
      accessed by foreigners when there was a large foreign population in the area
      under their domain. About 90% of the Welfare Centers in large cities had been
      consulted by foreigners. 3) Only about 30% of the Welfare Centers responding had
      employees who were competent in foreign languages, and guidebooks in foreign
      languages were available at less than 10% of the Welfare Centers. In most of the
      Welfare Centers that had staff competent in a foreign language, the language of
      competency was English. About 30% of the Welfare Centers responded that they
      could obtain the service of interpreters when they were consulted by foreigners
      who spoke languages which they could not understand. 4) The responding Welfare
      Centers were found to have had consultations by foreign children and pregnant
      women from all over the world. Consultations by South American and Asian
      nationals were found to be increasing rapidly. With respect to visa status, an
      increase was noted in the number of people who had married Japanese spouses. As
      to the age of children, the majority of those seen at Welfare Centers were
      infants. 5) There was an increased number of cases related to application of the
      Child Welfare Law, and the Maternal and Child Health Law.

PMID- 8755683
TI  - [Renovascular arterial hypertension. Importance of subtraction digital
      angiography in its diagnosis].
AB  - The objective of this study is to contribute to the positioning of the
      intravenous digital subtraction angiography (IVDSA) in the detection of
      morphologic abnormalities of renal arteries (RAs), susceptible to originate
      renovascular hypertension (RVH). The authors focus on the prevalence of RVH in
      the broad spectrum of systemic arterial hypertension. The definition of RVH is
      given and its diagnostic criteria are revisited. The angiography methods used in
      the evaluation of RAs morphologic abnormalities are described.

PMID- 8755684
TI  - [Clinical and echocardiographic assessment of surgical replacement of the aortic
      valve with lung autograft: results after 2 years].
AB  - OBJECTIVE: The goal of this study was to evaluate the clinical and
      echocardiographic results of a cohort of patients subjected to aortic valve
      replacement with pulmonary autograft (Ross procedure). DESIGN: We studied
      prospectively with clinical and echocardiographic evaluation all patients
      subjected to this type of aortic valve surgery, before operation,
      intraoperatively, before hospital discharge and at the end of this study in
      September 1994 and we analysed the evolution of the results during the follow-up
      period. PATIENTS: 22 consecutive patients 12 men and 10 women mean age 48 +/- 14
      years subjected to Ross operation between April 1992 and June 1994. METHODS:
      Patients were studied with transesophageal echocardiography intraoperatively and
      transthoracic echocardiography. Two-dimensional and M-mode evaluation, continuous
      and pulsed wave Doppler and color coded Doppler were performed, with assessment
      of the morphology and Doppler profile of both the autograft and the homograft in
      pulmonary position. RESULTS: No early or late mortality was registered, and apart
      two patients who were reoperated, all patients were asymptomatic in the last
      medical visit. There was no incidence of thromboembolic events even though no
      anticoagulation has been used. Aortic regurgitation was present in 14 patients,
      grade 1 in 11 patients and grade 2 in three. In the last echocardiogram performed
      the analysis of aortic flow, demonstrated absence of significant transvalvular
      gradient (maximal aortic gradient of 5.6 +/- 0.4 mmHg and mean aortic gradient of
      1.8 +/- 0.08 mmHg). Pulmonary regurgitation was absent in nine patients, and
      present in 13, considered trivial in all cases. CONCLUSIONS: These data suggest
      that this type of surgery has a low operative risk, with absence of
      thromboembolic complications and excellent clinical and echocardiographic
      results.

PMID- 8755685
TI  - [Reduction of the antihypertensive effects of enalapril by indomethacin. Its
      independence from renal sodium retention].
AB  - OBJECTIVE: To evaluate in hypertensive patients whether or not the sodium
      retaining effects of indomethacin can explain the indomethacin-induced
      attenuation of enalapril antihypertensive effects. DESIGN: Randomized, single
      blinded, placebo controlled study with a placebo phase (2 weeks) followed by
      enalapril 20 mg/d (4 weeks, once daily) and enalapril 20 mg + indomethacin 75
      mg/d (1 week). Enalapril dose increased up to 40 mg/d if inadequate response to
      20 mg. PATIENTS: Twenty-four patients with mild-moderated hypertension, showing
      an adequate response to enalapril (20-40 mg/d). METHODS: Blood pressure evaluated
      by "casual" methods and by 24-hour ambulatory blood pressure monitoring,
      measurement of 24-hour urinary sodium excretion and fractional excretion of
      sodium: at the end of placebo, enalapril and enalapril + indomethacin treatments.
      Determination of the correlations between the changes induced by indomethacin
      (when added to enalapril) on the blood pressure and on sodium excretion effects
      of enalapril. RESULTS: Enalapril significantly reduced casual blood pressure
      (systolic/diastolic) by 33/18 mmHg and 24-hour blood pressure by 20/9 mmHg. When
      added to enalapril, indomethacin attenuated (by 50%) the antihypertensive effects
      of enalapril and significantly decreased the 24-hour (from 120 +/- 11 mmol to 106
      +/- 10 mmol) and fractional excretion of sodium (from 1.11 +/- 0.09% to 0.75 +/-
      0.06%). However, the indomethacin-induced attenuation of enalapril hypotensive
      effects did not correlate with indomethacin-induced changes of sodium excretion.
      CONCLUSIONS: When indomethacin is administrated to hypertensive patients that are
      well controlled with enalapril, it produces a marked attenuation of enalapril
      hypotensive effects and produces sodium retention. However, the amount of the
      attenuation of the hypotensive effects of enalapril by indomethacin are
      completely independent of the amount of the indomethacin-induced sodium
      retention. These results suggest that the mechanisms involved in interaction
      between both drugs at the blood pressure domain are probably localized at an
      extra-renal level.

PMID- 8755686
TI  - [Antihypertensive effect of fosinopril in mild hypertension].
AB  - The aim of this double-blind randomized placebo-controlled study was to evaluate
      the antihypertensive and safety of fosinopril in mild essential hypertension.
      After a 2-week placebo period, patients received either placebo or fosinopril 20
      mg, once daily. Thirty-four patients finished the study (18 patients in the
      placebo group and 16 patients in the fosinopril group). Systolic blood pressure
      decreased from 160.1 +/- 22.1 mmHg to 156.0 +/- 24.2 in the placebo group (NS)
      and from 151.8 +/- 14.0 mmHg to 141.5 +/- 14.5 in the fosinopril group (p <
      0.005); diastolic blood pressure decreased from 100.1 +/- 2.4 mmHg to 94.3 +/-
      7.4 mmHg in the placebo group (p < 0.005) and from 100.8 +/- 4.8 mmHg to 88.1 +/-
      9.0 mmHg in the fosinopril group (p < 0.001). Mean decrease in diastolic blood
      pressure was 5.7 mmHg in the placebo group and 12.6 mmHg in the fosinopril group
      (p < 0.05). A statistically significant difference was seen between the
      percentage of controlled patients in the two groups: 16.6% in the placebo group
      vs 56.2% in the fosinopril group (p < 0.05). No statistically significant
      difference in biochemical parameters was seen between the two groups. Tolerance
      was good and no patients were withdrawn from the study for adverse events.

PMID- 8755687
TI  - [Anomalous insertion of mitral papillary muscles in obstructive hypertrophic
      myocardiopathy. Report of 2 cases].
AB  - Hypertrophic obstructive cardiomyopathy is a pathologic entity whose features are
      complex and diverse. Its surgical treatment generally requires myectomy. When the
      left ventricle outflow gradient is also due to mitral valve abnormalities, mitral
      valve replacement has been considered as the treatment of choice for the relief
      of the obstruction. We report two cases in which transesophageal echocardiography
      has allowed a good definition of this complex area of the heart and a better
      diagnosis and treatment of its components. Its use led to the diagnosis of
      abnormal papillary muscles inserted directly in the anterior leaflet of the
      mitral valve, with severe left ventricle outflow obstruction. Surgical treatment
      consisted of septal myectomy and excision of the muscles, thus preventing the
      need for mitral replacement. Systolic anterior motion of the mitral valve
      subsided and the outflow gradients became negligible. This new approach for the
      treatment of hypertrophic obstructive cardiomyopathy will be of benefit for
      patients in whom the anomalous insertion of the papillary muscles are recognized
      before surgery, thus preventing mitral valve replacement.

PMID- 8755688
TI  - [Thrombolysis in acute myocardial infarction].

PMID- 8755690
TI  - [Epidemiology, risk factors, and pathogeny of atrial fibrillation and atrial
      flutter].
AB  - Atrial fibrillation is a frequent arrhythmia which has a high prevalence after 65
      years of age, thus the typical patient's age is about 75. There are two atrial
      fibrillation predictors: traditional factors of cardiovascular risk (age, male
      sex, high blood pressure, diabetes), and structural heart disorders (heart
      failure, valvular heart disease). All preventive measures to reduce atrial
      fibrillation incidence, must be directed towards these factors. Additionally,
      left atrial size, ejection fraction and ventricular hypertrophy are
      echocardiographic predictors. Atrial fibrillation doubles the mortality rate and
      is related to an annual stroke rate of 4.5%. The stroke risk factors are: age,
      hypertension, diabetes, previous stroke, congestive heart failure, coronary heart
      disease, mitral stenosis, prosthetic heart valves and thyrotoxicosis. Left atrial
      size and ventricular disfunction are echocardiographic stroke risk factors. Each
      patient's risk can be stratified on the basis of these factors. All of this
      information is essential to handle the arrhythmia appropriately; this arrhythmia
      may be more important than has been thought. Atrial flutter is not very frequent
      and so it is less studied; however it is an arrhythmia with a similar clinical
      context to atrial fibrillation, although, probably, with a smaller embolic risk.

PMID- 8755691
TI  - [Electrophysiologic mechanisms of atrial fibrillation].
AB  - Atrial fibrillation is the most common arrhythmia in clinical practice. Atrial
      fibrillation is characterized by a complete disorganization in atrial electrical
      activity and sinus node pacemaker activity is lost. The physiopathological
      mechanisms of atrial fibrillation is based on the simultaneous presence of
      multiple wavelets in the atria. These multiple wavelets are continuously changing
      in localization, direction and duration resulting in a chaotic electrical
      activity. This theory has been confirmed by several studies using detailed
      mapping of the atria during atrial fibrillation. Also, the functional nature of
      the reentrant circuits during atrial fibrillation has also been demonstrated. For
      an episode of atrial fibrillation to perpetuate, the wavelength of the cardiac
      impulse has to be adapted to the length of the atria. Modifications of the
      wavelength by drugs may result in perpetuation or in termination of the atrial
      fibrillation episode.

PMID- 8755692
TI  - [Mechanism and location of typical atrial flutter. Information drawn from
      experimental models and clinical electrophysiology].
AB  - Several experimental models have been proposed to explain the
      electrocardiographic and electrophysiological characteristics of atrial flutter.
      In animal models based on anatomical obstacles, intercaval crush or Y like shaped
      lesion located in the right atrium, it has been possible to induce sustained
      atrial arrhythmias in which the entrainment criteria could be demonstrated.
      Additionally these tachycardias presented an atrialwave morphology similar to the
      F waves of type 1 or typical atrial flutter. Flutter type 2 could better be
      explained by models based on functional reentry like the leading circle. Typical
      atrial flutter in human, saw teeth morphology in inferior ECG leads, is though to
      be a circus movement located in the right atrium, as deduced of the analysis of
      activation sequence, resetting and entrainment phenomena from right and left
      atrium. Moreover the successful results of RDF ablation procedures confirm this
      idea. Nevertheless the delimitation of the anatomical boundaries of the reentry
      pathway remains inconclusive.

PMID- 8755693
TI  - [Electrocardiographic diagnosis and acute treatment of atrial fibrillation and
      flutter episodes].
AB  - Both atrial flutter and fibrillation are common arrhythmias in the clinical
      setting. Although we have been aware of them for decades, little has been known
      until recently about their triggering or maintenance mechanisms. The diagnosis of
      these arrhythmias lies largely in the electrocardiogram, which shows
      characteristic features of atrial electrical activity, leading to a correct
      diagnosis. Usually, some maneuvers such as adenosine infusion, carotidus sinus
      massage, etc., are required, in order to unmask the atrial activity, that are
      often obscured by the QRS complex or T wave. Several therapeutic options can be
      attempted for the acute termination of both atrial flutter and fibrillation
      episodes. The choice of one or another depends on some extent, on the clinical
      status of the patient during the arrhythmia, the presence of structural heart
      disease and the preceding arrhythmic history. Antiarrhythmic drugs are quite
      efficacious in the acute conversion of atrial fibrillation, but such an effect is
      not expected in atrial flutter. Drugs that depress AV nodal conduction can be
      used in both instances, as a therapeutic end-point or as a previous measure to
      the arrhythmia conversion. Direct current cardioversion is a good and efficacious
      option for both arrhythmias, however sedation is mandatory which, may be a
      contraindication in some patients. Rapid atrial pacing is an elegant and reliable
      method for the acute termination of atrial flutter of the common type, although a
      transvenous catheter insertion is needed.

PMID- 8755694
TI  - [Pharmacologic maintenance of sinusal rhythm and/or control of the ventricular
      response in patients with atrial fibrillation or flutter].
AB  - Atrial fibrillation is the most common cardiac arrhythmia and is usually
      responsible for symptoms requiring some treatment. Antiarrhythmic drugs are the
      first choice therapy, but their potential risks are significant. This together
      with their limited efficacy restricts their use. Antiarrhythmic drug use should
      be tailored; mainly according to the underlying heart disease. When reversion to
      sinus rhythm is not eligible, the adequate control of ventricular rate and the
      reduction of embolic risk are the therapeutic goals. Atrial flutter shows
      different behaviour regarding the very limited efficacy of antiarrhythmic drugs
      for reversion to and maintenance in sinus rhythm.

PMID- 8755695
TI  - [Antithrombotic therapy in atrial fibrillation].
AB  - The known risk of embolic events in patients with recurrent or chronic atrial
      fibrillation makes it mandatory to recommend oral anticoagulation in patients
      with rheumatic mitral valve disease, specially mitral stenosis to maintain an INR
      between 2.0 and 3.0. If despite this treatment recurrent embolism occurs, the
      dose of oral anticoagulants should be increased (INR between 2.5 and 3.5) or
      dipyridamole (200 to 400 mg/day) or aspirin (160 to 320 mg/day) should be added
      to dicoumarinic drugs. In patients that must be cardioverted either electrically
      or pharmacologically and who have been on atrial fibrillation for more than 2
      days, oral anticoagulation should be maintained for 3-4 weeks before
      cardioversion and for 3-4 weeks after regaining sinus rhythm. Transesophageal
      echocardiography may enable us to identify the group of patients with low risk
      for an immediate cardioversion. In patients under 60 years of age with atrial
      fibrillation and no evidence of associated cardiovascular abnormality (lone
      atrial fibrillation) the embolic risk is very low and antithrombotic therapy is
      probably not needed. In subjects over 60 years of age with a low risk profile
      (absence of previous stroke, heart failure or systemic hypertension) aspirin (300
      325 mg a day) seems to offer sufficient protection against embolic events. In
      patients at a higher embolic risk (history of previous cerebral ischemic attacks,
      heart failure of left ventricular dysfunction, systemic hypertension) oral
      anticoagulation unless contraindicated, should be recommended (INR 2.0-3.0). The
      role of other antithrombotic agents such as ticlopidine or triflusal to prevent
      embolic events in patients with atrial fibrillation is unknown.

PMID- 8755696
TI  - [Electric treatment of atrial fibrillation].
AB  - In the present manuscript the information concerning electrical therapy of atrial
      fibrillation (AF) to prevent its development and to control its consequences
      (excluding ablation which will be covered in separate manuscripts of this series)
      is reviewed. Both presently conventional approaches and those undergoing
      investigation will be considered, under three general headings. Electrical
      stimulation to prevent the development of AF. Based on non controlled studies
      comparing VVI stimulation with other modalities that include stimulation of the
      atria, it was suggested that atrial stimulation could prevent AF recurrences in
      patients with sinus node dysfunction. This concept has been questioned in recent
      studies. In contrast, the hypothesis that specific ways of atrial stimulation
      (stimulation at sites other than the high right atrium, multisite simultaneous or
      with certain "delays" atrial stimulation) may be more efficacious is presently
      under enthusiastic assessment. Electrical stimulation to control ventricular
      response. Despite the evidence that ventricular stimulation may contribute to
      regularization and rate control during AF, its quantitative value seems to be
      scarce and, thus, is not of regular use in practice. Automatic implantable atrial
      defibrillator. Both animal experiments and clinical studies have demonstrated
      that the atria can be defibrillated using intracavitary electrodes with less than
      3 joules in most cases, and without risk of inducing ventricular tachyarrhythmias
      as long as shocks are synchronized to the R wave and the preceding R-R interval
      is not short. Although an implantable atrial defibrillator is already undergoing
      clinical evaluation, the subject of tolerability of patients to shocks for non
      malignant arrhythmias is still controversial, since even low energy shocks seem
      to be painful.

PMID- 8755697
TI  - [Catheter ablation of atrial flutter and fibrillation].
AB  - The knowledge of the anatomic and functional bases of common flutter circuits has
      allowed the definition of an anatomic isthmus, between the inferior vena cava and
      the tricuspid valve, where radiofrequency application can interrupt the circuit.
      Some atypical flutter circuits are identical to common flutter circuits, but for
      an inverted rotation (clockwise), and these can be also ablated in the same
      isthmus. In cases of flutter (or reentrant tachycardia) due to surgical scars in
      the atrium, mapping supported with programmed stimulation, can define anatomic
      isthmuses, where ablation can also interrupt the circuit. There is still no
      definition of left atrial flutter circuits, that may guide ablation in these
      cases. Atrial fibrillation ablation is still in its infancy. Some initial
      experiences have tried to reproduce the division of atrial myocardium as in the
      maze procedure, and fibrillation was interrupted in a number of patients,
      submitted to very long procedures. There is still no clear definition of the
      muscular anatomy of the left atrium, in relation with the fibrillatory process,
      to guide the design of effective ablation lines. There are also technical
      problems to produce continuous, transmural ablation lines, that are not
      arrhythmogenic by themselves. The wide clinical application of ablation to treat
      atrial fibrillation is still in the distant future.

PMID- 8755698
TI  - [Surgical treatment of atrial fibrillation].
AB  - Atrial fibrillation is the most frequently found sustained arrhythmia. It
      increases the risk of thromboembolism and adversely affects cardiac performance
      because of loss of atrial kick. New surgical treatments of atrial fibrillation
      have been developed to ablate the origin of abnormal impulses on the atrium. The
      left atrial isolation and the corridor operation restores the regular rhythm, but
      do not reduce the risk of thromboembolism because the left atrium may continue to
      fibrillate. The maze operation has proven to be effective in both converting to
      sinus rhythm and regaining atrial contractility. However, this method is
      meticulous and time-consuming and takes more cardiac ischemic time, especially
      when other cardiac procedures are performed simultaneously.

PMID- 8755699
TI  - Token reinforcement, choice, and self-control in pigeons.
AB  - Pigeons were exposed to self-control procedures that involved illumination of
      light-emitting diodes (LEDs) as a form of token reinforcement. In a discrete
      trials arrangement, subjects chose between one and three LEDs; each LED was
      exchangeable for 2-s access to food during distinct posttrial exchange periods.
      In Experiment 1, subjects generally preferred the immediate presentation of a
      single LED over the delayed presentation of three LEDs, but differences in the
      delay to the exchange period between the two options prevented a clear assessment
      of the relative influence of LED delay and exchange-period delay as determinants
      of choice. In Experiment 2, in which delays to the exchange period from either
      alternative were equal in most conditions, all subjects preferred the delayed
      three LEDs more often than in Experiment-1. In Experiment 3, subjects preferred
      the option that resulted in a greater amount of food more often if the choices
      also produced LEDs than if they did not. In Experiment 4, preference for the
      delayed three LEDs was obtained when delays to the exchange period were equal,
      but reversed in favor of an immediate single LED when the latter choice also
      resulted in quicker access to exchange periods. The overall pattern of results
      suggests that (a) delay to the exchange period is a more critical determinant of
      choice than is delay to token presentation; (b) tokens may function as
      conditioned reinforcers, although their discriminative properties may be
      responsible for the self-control that occurs under token reinforcer arrangements;
      and (c) previously reported differences in the self-control choices of humans and
      pigeons may have resulted at least in part from the procedural conventions of
      using token reinforcers with human subjects and food reinforcers with pigeon
      subjects.

PMID- 8755700
TI  - Choice with certain and uncertain reinforcers in an adjusting-delay procedure.
AB  - A discrete-trials adjusting-delay procedure was used to investigate the
      conditions under which pigeons might show a preference for partial reinforcement
      over 100% reinforcement, an effect reported in a number of previous experiments.
      A peck on a red key always led to a delay with red houselights and then food. In
      each condition, the duration of the red-houselight delay was adjusted to estimate
      an indifference point. In 100% reinforcement conditions, a peck on a green key
      always led to a delay with green houselights and then food. In partial
      reinforcement conditions, a peck on the green key led either to the green
      houselights and food or to white houselights and no food. In some phases of the
      experiment, statistically significant preference for partial reinforcement over
      100% reinforcement was found, but this effect was observed in only about half of
      the pigeons. The effect was largely eliminated when variability in the delay
      stimulus colors was equated for 50% reinforcement conditions and 100%
      reinforcement conditions. Idiosyncratic preferences for certain colors or for
      stimulus variability may be at least partially responsible for the effect.

PMID- 8755701
TI  - Dynamics of time discrimination: II. The effects of multiple impulses.
AB  - According to a diffusion generalization model, time discrimination is determined
      by the frequency and recency of preceding intervals of time. A procedure for
      studying rapid timing was used to investigate whether pigeons' wait-time
      responses were sensitive to these factors. In Experiment 1 the number (two or
      eight) and spacing (consecutive or far apart) of 5-s interfood intervals (called
      impulses) intercalated in a series of 15-s interfood intervals (nonimpulses) were
      studied. Experiment 2 was identical to the first but the interfood intervals were
      increased by a factor of three. Overall, impulses shortened wait times in the
      next interfood interval. However, several impulses occurring in succession
      extended the localized effect of an impulse: Wait times following a set of eight
      close impulses were slow to recover to preimpulse levels. The results show that
      linear waiting is only an approximation to the dynamic process, and a process
      that is sensitive to events in an animal's remote past, such as the diffusion
      generalization model, provides a better account of rapid timing effects.

PMID- 8755702
TI  - Representing within-session response rates proportionally and entirely.
AB  - In this technical article, methods for collecting and representing response rates
      maintained by schedules of reinforcement are presented. First, the time in a
      session that each important event (e.g., responses, reinforcers) occurs is
      collected and stored by a computer. Another computer program is used, then, to
      convert each response to a percentage of the total responses in a session and to
      plot these percentages cumulatively as a function of the time in the session that
      they occurred. In this manner, response rates may be expressed proportionally
      (i.e., using the same y-axis scale regardless of absolute response rate) without
      requiring the arbitrary selection of an interval over which responses are
      aggregated and expressed relative to the entire-session rate. A property of these
      records is that deviations in the slope of the obtained record from the diagonal,
      which connects (x, y) = (start of session, 0%) to (x, y) = (end of session,
      100%), occurring at any point and for any duration, represent changes in the
      local response rate from the entire-session rate. This method of representing
      ongoing responding is illustrated by several records of key pecking of a pigeon
      on a variable-interval 60-s schedule of food reinforcement. Relative local
      response rates were also computed from these data at several levels of resolution
      (i.e., the time over which responses were aggregated), including the level
      typically employed by those interested in within-session changes in response
      rates.

PMID- 8755704
TI  - Vaccination coverage statistics for children up to two years of age in the United
      Kingdom.

PMID- 8755703
TI  - A second dose of MMR vaccine for children in the United Kingdom.

PMID- 8755705
TI  - Hepatitis A in homosexual men.

PMID- 8755706
TI  - Identification of pathogenic fungi.

PMID- 8755707
TI  - AIDS and HIV-1 infection in the United Kingdom: monthly report.

PMID- 8755708
TI  - Spectroscopic probe for the detection of local DNA bending at an AAA triplet.
AB  - Spectroscopic evidence of a DNA bend in solution is presented by analyzing model
      15-mer duplexes spin-labeled with the five-atom-tethered nitroxide DUAP located
      in the major groove. Three 15-mers containing AATT with DUAP enzymatically
      incorporated into three different positions yielded nearly identical line shapes
      while a fourth 15-mer containing AAATT produced an EPR spectrum with significant
      additional line broadening. These results are interpreted according to the
      dynamic cylinder model where the DNA dynamics are decoupled into overall and
      internal contributions. It is shown that the AAATT sequence induces a change in
      the internal dynamics characterized by local ordering of DUAP. The increase in
      ordering evident in 15-mers containing AAATT rather than AATT suggests that the
      former sequence gives rise to a bend toward the major groove resulting in spatial
      restriction of the probe.

PMID- 8755709
TI  - Structural characterization of the 1:1 adduct formed between the antitumor
      antibiotic hedamycin and the oligonucleotide duplex d(CACGTG)2 by 2D NMR
      spectroscopy.
AB  - 2D NMR spectroscopic methods have been used to determine the structure of the
      adduct formed between the antitumor antibiotic hedamycin and the
      oligodeoxyribonucleotide duplex d(CACGTG)2. Evidence for both intercalation and
      alkylation in the adduct was observed, and a model for the binding interaction
      was constructed based on intermolecular NOEs and distance-restrained molecular
      dynamics. In our computationally refined model, the anthrapyrantrione chromophore
      of hedamycin is intercalated between the 5'-CG-3' bases with the two aminosugar
      groups placed in the minor groove and the six carbon bisepoxide side chain
      located in the major groove. The anglosamine sugar attached at C8 is oriented in
      the 3' direction relative to the intercalation site, while the N,N
      dimethylvancosamine attached at C10 is oriented to the 5' side, with each
      aminosugar wedged between a guanine exocyclic amino group and one of the groove
      walls. The terminal epoxide carbon C18 is covalently bound to the N7 atom of the
      central guanine, as evidenced by lability of the C8 hydrogen of this purine upon
      reaction with hedamycin. Our binding model places the C10-attached N,N
      dimethylvancosamine of hedamycin in van der Waals contact with the alkylated
      strand. A strong NOE contact verifies the close proximity of the terminal methyl
      group (C19) of the bisepoxide side chain to the methyl group of the thymine on
      the 3' side of the alkylated guanine. This, in conjunction with other data,
      suggests hydrophobic interactions between the bisepoxide chain and the floor of
      the major groove may contribute to sequence recognition. Furthermore, it is
      proposed that the 5'-CGT sequence selectivity of hedamycin arises, in part, from
      complementarity in shape between the chromophore substituents and the major and
      minor groove at the binding site.

PMID- 8755710
TI  - Insertion and orientation of a synthetic peptide representing the C-terminus of
      the A1 domain of Shiga toxin into phospholipid membranes.
AB  - Shiga toxin is a bacterial protein composed of one A and five B subunits. Its A
      chain possesses a protease sensitive loop (Cys-242-Cys-261) that is cleaved to
      produce an enzymatically active A1 domain and an A2 fragment associated with its
      B subunit pentamer. The proposed mode of action of the toxin is linked to its
      retrograde transport to the ER lumen followed by the translocation of its
      catalytic A1 chain to the cytoplasmic side of the ER membrane. A signal sequence
      like domain (residues 220-246) which constitutes the C-terminus of the A1 chain
      precedes a region within the protease sensitive loop (residues 247-258) that
      contains known and putative cleavage sites. Two peptides corresponding to this C
      terminus (residues 220-246) were chemically synthesized to investigate if this
      signal sequence-like domain can interact with membranes. Such a property may
      provide a clue to the mechanism of translocation of the A1 domain across the ER
      membrane. The first peptide represented the native sequence, which includes a
      naturally occurring cysteine at position 242 and provided a thiol moiety for the
      attachment of a spinlabel. A second peptide was designed to contain a single
      tryptophan residue (Ile232Trp) located within the hydrophobic core of the
      sequence which served as an intrinsic fluorescence probe. The interactions of
      both peptides with lipid vesicles were analyzed by circular dichroism,
      fluorescence, and EPR spectroscopy. The peptides lack structure in aqueous
      buffers and adopted an alpha-helical geometry when bound to negatively charged
      lipid vesicles. The addition of lipid vesicles to a solution of the tryptophan
      containing peptide results in a blue shift in the wavelength of its fluorescence
      maxima as well as an increase in fluorescence intensity at 335 nm, suggesting
      that the hydrophobic core of this A1 peptide relocated to a nonpolar environment.
      EPR measurements of a proxyl-labeled analog of the peptide (introduced at Cys
      242) indicated a decreased mobility of a fraction of the proxyl probe in the
      presence of lipid vesicles. At pH 7, the membrane-bound probe was completely
      reduced by ascorbate trapped inside vesicles but only partially reduced by
      ascorbate added outside the vesicles, suggesting that the C-terminal region of
      the peptide traversed the membrane bilayer or relocated close to the surface of
      its inner lipid leaflet. Finally, the peptide was shown to insert into lipid
      vesicles, causing the release of calcein at a high peptide:lipid ratio. These
      results suggest that the C-terminal tail of the A1 chain may anchor this domain
      into the ER membrane.

PMID- 8755712
TI  - VHR and PTP1 protein phosphatases exhibit remarkably different active site
      specificities toward low molecular weight nonpeptidic substrates.
AB  - The dual-specificity protein phosphatases have recently been shown to act as key
      regulators of mitogenic signaling pathways as well as of the cell cycle process.
      The are unusual catalysts in that they can utilize protein substrates containing
      phosphotyrosine as well as phosphoserine/threonine. The dual-specificity
      phosphatases and the protein tyrosine phosphatases (PTPase) share the active site
      motif (H/V)C(X)5R(S/T) but display little amino acid sequence identity outside of
      the active site. Although the dual-specificity phosphatases and the PTPases
      appear to bring about phosphate monoester hydrolysis through a similar mechanism,
      there is very limited information about the structural features that control the
      substrate specificity for the two groups of enzymes. As a first step in the
      development of selective dual-specificity phosphatase inhibitors, we have
      examined the active site substrate specificity of the human dual-specificity
      phosphatase, VHR [for VH1-Related; Ishibashi et al. (1992) Proc. Natl. Acad. Sci.
      U.S.A. 89, 12170-12174]. Like the tyrosine-specific PTP1, VHR also preferentially
      catalyzes the hydrolysis of aromatic phosphates. However, we demonstrate herein
      that relatively modest changes in the substitution patterns on the phosphorylated
      aromatic nucleus generates dramatic, and differential, swings in substrate
      selectivity for VHR and PTP1. For example, VHR appears to be significantly more
      accommodating than PTP1 toward sterically-demanding substrates. Thus, the active
      site specificity of these two protein phosphatases is decidedly dissimilar. In
      addition, we have also identified several low molecular weight compounds that are
      more efficient substrates than the most potent peptidic substrates ever reported
      for VHR. Finally, we have shown that the Michaelis constants exhibited by these
      substrates are accurate assessments of enzyme affinity. Consequently, it should
      be possible to develop phospatase-selective inhibitors based upon the distinct
      substrate specificities of these enzymes.

PMID- 8755711
TI  - Backbone dynamics, amide hydrogen exchange, and resonance assignments of the DNA
      methylphosphotriester repair domain of Escherichia coli Ada using NMR.
AB  - The 10kDa amino-terminal fragment of Escherichia coli Ada protein (N-Ada10)
      repairs methyl phosphotriesters in DNA and possesses a tightly bound zinc ion.
      The complete resonance assignments of this protein domain have been obtained
      using multidimensional homonuclear and heteronuclear NMR experiments. The
      assignments served to study the internal mobility of this protein domain via 15N
      relaxation experiments. This involved the measurement of longitudinal and
      transverse 15N relaxation rates, as well as the amide proton solvent exchange
      rates. Relaxation rates in the rotating frame, R1 rho, of 15N nuclei were
      measured at different spin-lock field strengths, leading to the detection of two
      slow conformational exchange processes at Gly-25 and Gln-73. For the latter,
      which is next to the active site of this protein domain, the characteristic time
      of this process was found to be around 60 microseconds. The other relaxation
      experiments unveiled some regions of fast internal motions, faster than the
      overall correlation time. These motions were found in the N- and C- terminal
      tails, in segment 33-35 which forms the turn between beta-strands S1 and S2, and
      residues 47-52 located in a long loop preceding strand S3. The latter loop
      belongs to the potential DNA binding surface of N-Ada10. While the structure from
      residue 18 to residue 26 appears not well defined in the calculated structure,
      the relaxation experiments do not indicate higher mobility for this region.
      Residues at the N-terminal portion, including the first helix, the sequentially
      adjacent loop, and part of the second helix, exhibit internal motions close to
      the time scale of the overall rotational correlation time. This appears to be
      related to the fact that the first helix has no hydrogen bonds or salt bridges to
      the rest of the protein and is stabilized only by the involvement of some of its
      side chains in a hydrophobic core consisting of the side chains of two
      phenylalanines, a tryptophan, a leucine, and a valine. The four cysteines which
      bind the zinc show motions on different time scales ranging from microseconds to
      picoseconds. Thus the motions in the immediate region around the bound zinc of
      the DNA methyl phosphotriester repair domain are of relatively small amplitude
      but take place over a wide time range. On the other hand, high mobility is found
      in the turn connecting S1 and S2 and in the loop preceding S3, regions of the
      potential DNA binding surface.

PMID- 8755714
TI  - HIV-1 genome dimerization: formation kinetics and thermal stability of dimeric
      HIV-1Lai RNAs are not improved by the 1-232 and 296-790 regions flanking the
      kissing-loop domain.
AB  - The genome of all retroviruses consists of two identical RNAs noncovalently
      linked near their 5' end. Dimerization of genomic RNA is thought to modulate
      several steps in the retroviral life cycle, such as recombination, translation,
      and encapsidation. The kissing-loop model of HIV-1 genome dimerization posits
      that the 233-285 region of the HIV-1 genome, by forming a hairpin and initiating
      dimerization through a loop-loop interaction, is at least the core dimerization
      domain of HIV-1 RNA. This region is called the kissing-loop domain. In addition,
      it can be argued that sequences within the 296-401 region [Paillart et al. (1994)
      J. Biol. Chem. 269, 27486-27493] or 5' of the primer binding site [Laughrea &
      Jette (1996) Biochemistry 35, 1589-1598] might play some role in the dimerization
      process. Accordingly, we have studied the effect of regions 1-232 and 296-790 on
      the dimerization kinetics and thermal stability of HIV-1Lai RNAs containing the
      kissing-loop domain (HIV-1Lai is a typical representative of North American and
      European HIV-1 viruses). Experiments conducted at high and low ionic strength
      indicate that these regions have no strongly positive effect on the dimerization
      process. Our experiments also indicate that the kissing-loop domain of HIV-1Lai
      has an apparent dissociation temperature 13 degrees C higher than that of the HIV
      1Mal kissing-loop domain (HIV-1Mal is a Central African virus whose kissing-loop
      domain has a "weak" GUGCAC autocomplementary sequence). Because the 296-401
      region of HIV-1Mal RNA stabilizes dimeric RNAs by < or = 12 degrees C (Paillart
      et al., 1994), we infer that the contributions of sequences downstream of U295
      are (at best) concealed in HIV-1Lai and in most American and European HIV-1
      viruses, i.e., in viruses whose kissing-loop domain is characterized by a
      "strong" GCGCGC autocomplementary sequence.

PMID- 8755713
TI  - Structure of a DNA duplex that contains alpha-anomeric nucleotides and 3'-3' and
      5'-5' phosphodiester linkages: coexistence of parallel and antiparallel DNA.
AB  - We report a comparative spectroscopic study of a novel self-complementary duplex
      decamer, d(GCGAAT-3'-3'-(alpha T)-5'-5'-CGC)2, in which an alpha-anomeric
      nucleotide has been inserted into the sequence in a parallel orientation via 3'
      3' and 5'-5' phosphodiester bonds, and its unmodified B-DNA analog,
      d(GCGAATTCGC)2. Plots of the hyperchromicity and circular dichroism of these
      oligonucleotides are virtually identical, indicating that the overall base
      stacking and handedness are preserved in the alpha duplex. Thermodynamic
      parameters extracted from UV melting experiments show that the alpha duplex is
      only slightly less stable than the control. A near complete set of 1H and 31P
      nuclear magnetic resonance (NMR) assignments were obtained for both duplexes
      using classical one- and two-dimensional approaches. Several lines of evidence,
      in particular, imino 1H, 31P, nuclear Overhauser enhancement, and deoxyribose
      ring proton spin-spin coupling data, convincingly demonstrate that the overall
      structural integrity of the alpha and control duplexes are quite comparable, with
      any perturbations in the former localized to the regions of the construct
      encompassing the alpha-nucleotide and the unique backbone linkages. Specifically,
      the alpha duplex exhibits normal Watson-Crick type base pairing, it remains
      antiparallel except at the inverted nucleotide, all bases are in the anti
      orientation, and the sugar ring puckering is predominantly "S"-type. However, the
      J-coupling information for the alpha-nucleotide and the neighboring (3') cytidine
      are notably different, and reflect a decrease in the amplitude of the sugar
      pucker in alpha T7, and a significant shift in the conformational equilibrium of
      the furanose ring in C8 toward the "N"-type pucker. The feasibility of
      synthesizing oligodeoxynucleotides containing a combination of alpha sugars and
      short parallel stranded segments, their propensity for forming stable duplexes,
      and the structural insights into such complexes reported here are of potential
      importance in the area of antisense therapy.

PMID- 8755715
TI  - Kinetic basis for the substrate specificity during hydrolysis of phospholipids by
      secreted phospholipase A2.
AB  - Kinetics of hydrolysis of aqueous dispersions of arsono-, sulfo-, phosphono- and
      phospholipids by phospholipase A2 from pig pancreas are characterized in terms of
      interfacial rate and equilibrium parameters. The enzyme with or without calcium
      binds with high affinity to the aqueous dispersions of the four classes of
      anionic lipids and shows the same general kinetic behavior. The rate of
      hydrolysis of anionic substrates does not show an anomalous change at the
      critical micelle concentration because the enzyme is present in aggregates even
      when bulk of the substrate is dispersed as a solitary monomer. Apparent
      affinities of the enzyme for the interface of different anionic lipids are
      virtually the same. Also, affinities of these substrates for the active site of
      the enzyme at the interface are comparable. However, a significant change in the
      catalytic turnover rate is seen as the sn-3 phosphodiester group is modified; the
      apparent maximum rate at saturating bulk substrate concentration, V(M)app values,
      increase in the order: homo- and arsonolipids < sulfo- < phosphono- <
      phospholipids. Not only the basis for the sn-2 enantiomeric selectivity but also
      the decrease in the rate of hydrolysis with the increasing chain length is due to
      a decrease in the value of V(M)app. Results show that even when the bulk
      concentration of anionic phospholipid is below cmc, hydrolysis occurs in
      aggregates of enzyme and substrate where the chemical step of the turnover cycle
      remains rate-limiting, which provides a basis for the assumption that V(M)app is
      directly related to Kcat. The fact that Kcat depends on the nature of the head
      group (phosphate, phosphonate, sulfate, arsonate) implies that the head group
      plays a critical role in the rate-limiting chemical step of the catalytic cycle,
      possibly during the decomposition of the tetrahedral intermediate. The
      significance of these results for the microscopic steady-state condition for
      hydrolysis at the micellar interface, mechanism of esterolysis by phospholipase
      A2, and inhibitor design are discussed.

PMID- 8755716
TI  - Mercaptide formed between the residue Cys70 and Hg2+ or Co2+ behaves as a
      functional positively charged side chain operative in the Arg70-->Cys mutant of
      the metal-tetracycline/H+ antiporter of Escherichia coli.
AB  - The bacterial tetracycline/H+ antiporter (TetA) mediates active efflux of a
      chelation complex of tetracycline with a divalent cation such as Mg2+, Co2+, or
      Mn2+ [Yamaguchi, A., Udagawa, T., & Sawai, T. (1990a) J. Biol. Chem. 265, 4809
      4813]. The positive charge of Arg70 in the antiporter is important for the
      transport function [Yamaguchi, A., Someya, Y., & Sawai, T. (1992c) J. Biol. Chem.
      267, 19155-19162]. Out of six site-directed mutants of Arg70, only the Lys70
      mutant retained moderate transport activity, whereas the Ser70, Ala70, Trp70,
      Leu70, and Asp70 mutants had no or extremely low transport activity. In this
      study, we constructed the Cys70 mutant and found that the Cys70 mutant showed,
      unexpectedly, a significant activity comparable to that of the Lys70 mutant in
      the presence of Co2+ ions, whereas it showed very low activity as well as the
      Ala70 mutant in the presence of Mg2+ or Mn2+ ions. Hg2+, which is known to be a
      cysteine specific modifier but has no ability to form a complex with
      tetracycline, caused a dramatic increase in the Vmax value of Co(2+)-dependent
      tetracycline transport mediated by the Cys70 mutant without affecting the k(m)
      value, whereas activities of the wild-type and the Lys70 and Ala70 mutants were
      not affected by Hg2+, Hg2+ alone without Co2+ could not support the transport
      activity at all, because Hg2+ does not form a chelation complex with
      tetracycline. These observations suggest that a mercaptide formed between the SH
      group of Cys70 and Hg2+ or Co2+ works as a positively charged side chain like
      that of Arg or Lys. When the SH group of the Cys70 mutant was masked with
      modification by sulfhydryl reagents, the residual activity was no longer affected
      by Hg2+. Inversely, when the Cys70 mutant was preincubated with Hg2+, it was
      protected from the inactivation by sulfhydryl reagents. These observations also
      confirm the mercaptide formation between the Cys70 and a divalent cation as a
      functional side chain.

PMID- 8755717
TI  - Identification of myosin III as a protein kinase.
AB  - Drosophila ninaC gene encodes myosin homologous proteins which are classified as
      myosin III of the myosin superfamily, yet the physiological and biochemical
      function of myosin III has not characterized. We report here that myosin III does
      exhibit protein kinase activity. The kinase homologous domain (MYOIIIPK) of
      myosin III was expressed in the baculovirus expression system and purified to
      homogeneity. MYOIIIPK phosphorylated a number of proteins including myosin III
      p132 and smooth muscle myosin regulatory light chain (LC20), suggesting that
      myosin III is a multifunctional protein kinase. The phosphoamino acid analysis
      revealed that myosin III is a serine/threonine kinase but not a tyrosine kinase.
      The observation that MYOIIIPK phosphorylates myosin III suggests that the
      autophosphorylation might play a role for the regulation of myosin III function.
      This is the first direct demonstration of kinase activity for the myosin III
      class.

PMID- 8755718
TI  - Identification of PK-A phosphorylation sites in the carboxyl terminus of L-type
      calcium channel alpha 1 subunits.
AB  - Full length L-type calcium channel alpha 1 subunits are rapidly phosphorylated by
      protein kinase A (PK-A) in vitro and in vivo at sites located in their long
      carboxyl terminal tails. In skeletal muscle, heart, and brain the majority of
      biochemically isolated alpha 1 subunits lacks these phosphorylation sites due to
      posttranslational proteolytic processing. Truncation may therefore modify the
      regulation of channel activity by PK-A. We combined site-directed mutagenesis and
      heterologous expression to investigate the extent to which putative cAMP
      dependent phosphorylation sites in the C-terminus of alpha 1 subunits from
      skeletal muscle, heart, and brain are phosphorylated in vitro. The full length
      size form of wild-type and mutant calcium channel alpha 1 subunits was obtained
      at high yield after heterologous expression in Saccharomyces cerevisiae. Like in
      fetal rabbit myotubes [Rotman, E.I., et al. (1995) J. Biol. Chem. 270, 16371
      16377], the rabbit skeletal muscle alpha 1 C-terminus was phosphorylated at
      serine residues 1757 and 1854. In the carboxyl terminus of alpha 1S from carp
      skeletal muscle and alpha 1C from rabbit heart a single serine residue was
      phosphorylated by PK-A in vitro. The C-terminus of alpha 1D was phosphorylated at
      more than one site. Employing deletion mutants, most of the phosphorylation ( >
      70%) was found to occur between amino acid residues 1805 and 2072. Serine 1743
      was identified as additional phosphorylation site in alpha 1D. We conclude that
      in class S and C calcium channels the most C-terminal phosphorylation sites are
      substrate for PK-A in vitro, whereas in class D calcium channels phosphorylation
      also occurs at a site which is likely to be retained even after posttranslational
      truncation.

PMID- 8755719
TI  - Activation of phospholipase A2 by amyloid beta-peptides in vitro.
AB  - Amyloid beta-peptides (A beta) are centrally involved in the pathogenesis of
      Alzheimer's disease. Using secretory phospholipase A2 (PLA2) from porcine
      pancreas as a model and in the presence of a limiting Ca2+ concentration of
      approximately 50 nM, the synthetic peptide A beta 1-42 activates the hydrolysis
      of the pyrene-labeled acidic phospholipid analog 1-palmitoyl-2-[(pyren-1
      yl)]hexanoyl-sn-glycero-3-phosphoglycerol (PPHPG) maximally 2.3-fold, whereas an
      inhibition of PLA2 action by 50% on the corresponding phosphatidylcholine
      derivative (PPHPC) was observed. The above effects were evident at 0.24 nM A beta
      1-42 corresponding to A beta 1-42:phospholipid and A beta 1-42:PLA2 molar ratios
      of 1:10 650 and 1:7.6, respectively. The presence of 10 mol % 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphoglycerol (POPG) in PPHPC reversed the inhibitory
      effect of A beta 1-42 peptide and for these vesicles the hydrolytic activity of
      PLA2 toward the fluorescent phosphatidylcholine was enhanced approximately 1.8
      fold by A beta 1-42. In contrast, inclusion of 10 mol % POPG into PPHPG did not
      influence either the hydrolytic rate toward the latter lipid or the activating
      effect of A beta 1-42. Ca2+ concentrations exceeding 15 microM abolished the
      enhancing effect of A beta 1-42 on the hydrolysis of PPHPG whereas a slight
      activation of PPHPC hydrolysis now became evident. With limiting [Ca2+]
      preaggregated A beta 1-42 enhanced the hydrolysis of both PPHPG as well as PPHPC
      but the peptide concentrations required were higher by 3-4 orders of magnitude.
      The synthetic peptide A beta 25-35 corresponding to the hydrophobic membrane
      spanning segment of the beta amyloid precursor protein activated PLA2 when using
      PPHPG as a substrate; however, compared to A beta 1-42 the extent of activation
      was less (approximately 2-fold) and required higher (1 nM) peptide. A beta 25-35
      did not affect the hydrolysis of the phosphatidylcholine derivative. The
      hydrophilic peptide A beta 1-28 had no effect on PLA2-catalyzed hydrolysis of
      either PPHPG or PPHPC under the conditions used in the present study.
      Interestingly, the above activating effects of A beta 1-42 and A beta 25-35 on
      PLA2-catalyzed hydrolysis of the acidic phospholipid substrate parallel their
      toxicity on cultured neurons whereas A beta 1-28 had no influence either on
      cultured cells or on PLA2 activity.

PMID- 8755720
TI  - ptl-1, a Caenorhabditis elegans gene whose products are homologous to the tau
      microtubule-associated proteins.
AB  - The tau microtubule-associated proteins are axonal proteins that have been
      implicated in axonal outgrowth, microtubule spacing, and microtubule bundling.
      Moreover, tau is the major structural component of the paired helical filaments
      present in the brains of Alzheimer's disease patients. The Caenorhabditis elegans
      Genome Sequencing Consortium identified a genomic sequence with homology to the
      repeat region of tau. PCR, Northern analyses, and cDNA sequencing were used here
      to identify transcripts containing the tau homology region. The gene that encodes
      these transcripts was named ptl-1 for protein with tau-like repeats. The ptl-1
      transcript, like mammalian tau transcripts, is alternatively spliced to produce
      messages that encode proteins with variable numbers of repeats. The predicted ptl
      1 products have strong sequence homology to tau over the repeat region and are
      similar to tau in several other important respects including size, amino acid
      content, charge distribution, predicted secondary structure, hydrophobicity, and
      flexibility. Both proteins contain several potential glycosylation sites and
      numerous phosphorylation sites. Bacterially expressed PTL-1 bound to microtubules
      in vitro. These results show that tau-like proteins evolved early and suggests
      that they may be present in many different phyla. C. elegans is a powerful system
      amenable to genetic, molecular, and cellular analysis in which to study the
      functions of this important class of proteins.

PMID- 8755721
TI  - Elucidating the mechanism of nucleotide-dependent changes in the redox potential
      of the [4Fe-4S] cluster in nitrogenase iron protein: the role of phenylalanine
      135.
AB  - Nucleotide binding to the nitrogenase iron (Fe) protein results in a lowering of
      the redox potential of its [4Fe-4S] cluster by over 100 mV, and this is thought
      to be essential for electron transfer to the molybdenum-iron (MoFe) protein for
      substrate reduction. This work presents evidence for an important role of the
      strictly conserved phenylalanine at position 135, located near the [4Fe-4S]
      cluster of nitrogenase Fe protein, in defining both the redox potential and the
      nucleotide-induced changes in the redox potential of the [4Fe-4S] cluster. Phe
      135 was changed by means of site-directed mutagenesis to the amino acids Tyr
      (F135Y), Ile (F135I), Trp (F135W), and His (F135H), and the altered proteins were
      purified to homogeneity. Minor changes in the UV/visible and EPR spectra arising
      from the [4Fe-4S] cluster were detected in the altered proteins, while dramatic
      changes were observed in the visible region circular dichroism (CD) spectrum,
      suggesting that Phe 135 contributes significantly to the chiroptical properties
      of the [4Fe-4S] cluster. Likewise, significant changes in the redox potentials of
      the Phe altered Fe proteins were observed, with shifts of +50 to +120 mV compared
      to the redox potential of the wild-type Fe protein (-300 mV). The shifts in redox
      potential for the altered Fe proteins appeared to correlate with changes in
      isotropically shifted proton NMR resonances assigned to cluster ligands. All of
      the Phe 135 altered Fe proteins were found to bind either MgADP or MgATP, while
      the reduced and oxidized states of the F135W and F135H altered Fe proteins had
      significantly higher affinities for binding MgATP when compared to the wild-type
      Fe protein. While MgATP binding to the wild-type and Phe 135 altered Fe proteins
      resulted in approximately -100 mV shifts in the redox potentials for all
      proteins, MgADP binding resulted in only -30 to -50 mV shifts for the altered
      proteins compared to a -160 mV shift for the wild-type Fe protein. The current
      results suggest that Phe 135 is important in defining the redox potential of the
      [4Fe-4S] cluster in the Fe protein and influences the MgADP (but not MgATP)
      induced modulation of the redox potential.

PMID- 8755722
TI  - State transitions or delta pH-dependent quenching of photosystem II fluorescence
      in red algae.
AB  - Fluorescence changes attributed to state transitions have been shown to exist in
      phycobilisome-containing organisms. Contradictory conclusions have been derived
      from studies about the mechanism of state transitions carried out either in
      cyanobacteria or in red algae. In this paper, fluorescence changes induced by
      light 1 and light 2 are reinvestigated in a unicellular red alga, Rhodella
      violacea, by performing 77 K fluorescence spectra and fluorescence yield
      measurements at room temperature in the presence of uncouplers and inhibitors of
      the electron transfer. We show that transfer of light 1-adapted cells to light 2
      (green light) induces a large quenching of photosystem II which is suppressed by
      subsequent incubation in light 1 (far-red or blue light). The level of the
      photosystem I-related fluorescence does not change during these transfers. We
      demonstrate that the large quenching of photosystem II induced by low intensities
      of green light is completely suppressed by addition of NH4Cl, an uncoupler that
      inhibits ATP synthesis by canceling the delta pH across the membrane. DCCD, which
      is an inhibitor of the ATPase that swells the delta pH, maintains the quenched
      state even under light 1 illumination. The opposite effects of DCMU and DBMIB on
      state transitions are demonstrated to be due to a suppression (by DCMU) or
      maintenance (by DBMIB) of the delta pH and not to change in the redox state of
      the plastoquinone. We conclude that, in R. violacea, the fluorescence change
      commonly associated with state 2 transition is in fact a delta pH-dependent
      quenching. This type of quenching has always been associated with near-saturating
      light intensities. Here, we show that very low intensities of a light that
      activates only the photosystem II induce a delta pH across the membrane that is
      not dissipated since the ATPase is not activated. The delta pH is dissipated only
      under conditions in which the photosystem I turns, confirming that the
      thioredoxin must be reduced to activate the ATPase. We suggest that the
      fluorescence changes, induced by various light conditions, in cyanobacteria and
      red algae could be associated with different phenomena.

PMID- 8755723
TI  - A pH-dependent polarity change at the binuclear center of reduced cytochrome c
      oxidase detected by FTIR difference spectroscopy of the CO adduct.
AB  - A pH-dependent polarity change at the heme-copper binuclear center of the aa3
      type cytochrome c oxidase from Rhodobacter sphaeroides has been identified by low
      temperature FTIR difference spectroscopy. "Light"-minus-"dark" FTIR difference
      spectra of the fully reduced CO-enzyme adduct were recorded at a range of pH, and
      the dominance of different populations of bound CO, alpha and beta, was found to
      vary with pH. An apparent pKa of about 7.3 for the transition was obtained. The
      alpha and beta forms are differentiated by different polarities at the heme
      copper binuclear center of the enzyme, sensed by the stretching frequencies of CO
      bound either to the heme alpha 3 Fe or to CuB. Several site-directed mutants in
      the vicinity of the heme-copper center are shown to favor either the alpha or the
      beta forms of the enyzme, suggesting that what is being monitored is an
      equilibrium between two conformations of the reduced form of the oxidase. Recent
      resonance Raman evidence has been presented demonstrating that the alpha and beta
      forms of the R. sphaeroides oxidase exist at room temperature; therefore, the pH
      dependent change in the polarity in the vicinity of the heme-copper center may be
      functionally significant.

PMID- 8755724
TI  - Role of Ser457 of NADPH-cytochrome P450 oxidoreductase in catalysis and control
      of FAD oxidation-reduction potential.
AB  - Site-directed mutagenesis of Ser457 of NADPH-cytochrome P450 oxidoreductase
      demonstrates that this residue plays a major role in both hydride transfer from
      NADPH to FAD and modulation of FAD redox potential. Substitution of Ser457 with
      alanine or cysteine decreases the rates of reduction of the substrates cytochrome
      c and potassium ferricyanide approximately 100-fold, while substitution with
      threonine produces a 20-fold decrease in activity. No changes are observed in
      k(m)NADPH, KiNADP+, or flavin content, indicating that these substitutions have
      no effect on cofactor binding but affect catalysis only. k(m)cyt c values are
      decreased in parallel with the observed decreases in the rates of the reductive
      half-reaction. Stopped-flow studies with the S457A mutant show a 100-fold
      decrease in the rate of flavin reduction. The primary deuterium isotope effect on
      Kcat for cytochrome c reduction increases from 2.7 for the wild-type enzyme to
      9.0 for the S457A mutant, consistent with a change in the rate-determining step
      from NADP+ release in the wild-type enzyme to hydride transfer in the S457A
      mutant. The primary deuterium isotope effect on K1 for flavin reduction at high
      ionic strength (I = 535 mM) increases from 12.2 for the wild-type enzyme to > 20
      for the S457A mutant, consistent again with an increase in the relative rate
      limitation of hydride transfer. Furthermore, anaerobic titration of S457A
      indicates that the redox potential of the FAD semiquinone has been decreased.
      Data presented in this study support the hypothesis that Ser457 is involved in
      hydrogen bonding interactions which stabilize both the transition state for
      hydride transfer and the reduced FAD.

PMID- 8755726
TI  - Cu(II)-inhibitory effect on photosystem II from higher plants. A picosecond time
      resolved fluorescence study.
AB  - The influence of Cu(II) inhibition on the primary reactions of photosystem II
      (PSII) electron transport was studied by picosecond time-resolved fluorescence on
      isolated PSII membranes. The fluorescence decay from Cu(II)-inhibited PSII
      centers showed a dominant amplitude of a fast phase (100-300 ps) similar to PSII
      centers in the uninhibited "open state" and minor contributions of components
      around 600 ps and 2.6 ns. These data indicate efficient primary charge separation
      in PSII membranes incubated with Cu(II). The quantum yield of primary reactions
      in the inhibited PSII centers was similar to that of "open" PSII centers. Kinetic
      analysis of the decay curves in the framework of the exciton/radical pair
      equilibrium model showed no significant changes in the rate constants associated
      with the charge separation/recombination equilibrium. However, in closed centers
      (QA reduced), a decrease in the rate constant K23, associated with the back
      reaction of a relaxed radical pair, by a factor of 4 was calculated. The free
      energy losses upon primary charge separation (delta G1) and during subsequent
      radical pair relaxation (delta G2) were also determined in Cu(II)-inhibited
      centers and were compared with uninhibited centers. No changes in the delta G1
      values and a significant decrease in the delta G2 values were found as compared
      with those of control PSII centers in the "closed" state. These data indicate
      that Cu(II) does not affect primary radical pair formation, but strongly affects
      the formation of a relaxed radical pair, by neutralizing the negative charge on
      QA- and eliminating the repulsive interaction between Pheo- and QA- and/or by
      modifying the general dielectric properties of the protein region, surrounding
      these cofactors. Moreover, a close attractive interaction between Pheo-, QA-, and
      Cu2+ can be proposed. Our results are in good agreement with very recent EPR
      results indicating an additional effect of Cu2+ on the acceptor side [Jegerschold
      et al. (1995) Biochemistry 34, 12747-12758].

PMID- 8755725
TI  - V92A mutation altered the folding propensity of chicken apocytochrome c and its
      interaction with phospholipids.
AB  - Chicken apocytochrome c has been shown to possess a much stronger tendency to
      fold spontaneously in aqueous solution than the equivalent enzyme from other
      species. In the present work, the amino acid that determines its folding ability
      was elucidated by site-directed mutagenesis. Wild-type chicken apocytochrome c
      and three mutants V92A, S103A, and V92A/S103A were expressed in Escherichia coli.
      The wild-type apoprotein and S103A exhibited the same folding property during
      dialysis renaturation processes as that chemically prepared from chicken
      cytochrome c, while those containing V92A mutation did not. Quantitative studies
      by 2,2,2-trifluoroethanol (TFE) and sodium perchlorate (NaClO4) titration
      demonstrated that the V92A mutation decreased the helix content that could be
      induced and confirmed that valine 92 is the major determinant of the folding
      propensity of chicken apocytochrome c. Furthermore, CD spectra, turbidity
      measurements, and a translocation assay on a model membrane system showed that
      the V92A mutation also drastically altered the conformation of apocytochrome c
      after being incorporated into lipid bilayer and decreased the aggregation of
      phospholipid vesicles after association of the apoprotein, thus rendering the
      molecule more competent for translocation across the membrane. Our results showed
      that a single amino acid substitution could radically alter the folding
      propensity of an unfolded polypeptide chain and thus influence the conformation
      following its insertion into phospholipid bilayer.

PMID- 8755727
TI  - Tumor suppressor p16INK4A: structural characterization of wild-type and mutant
      proteins by NMR and circular dichroism.
AB  - The tumor suppressor p16INK4A with eight N-terminal amino acids deleted
      (p16/delta 1-8) was expressed in Escherichia coli without any fusion artifacts
      and purified. The integrity of p16/delta 1-8 was confirmed by mass spectrometry,
      and its activity was demonstrated by in vitro cdk4 inhibition assay. Various
      physical methods were used to characterize the molecular and structural
      properties of p16/delta 1-8. The protein was found to oligomerize in vitro, as
      demonstrated by gel electrophoresis, mass spectrometry, and NMR. Various
      approaches, including changes of concentration and pH, additions of salts,
      detergents, and various organic solvents, and construction of a C-terminal
      deletion mutant and a cysteine mutant were used to try to reduce the extent of
      oligomerization. Only decreasing the protein concentration was found to reduce
      oligomerization. The affinity between p16 molecules in vivo was demonstrated by
      the yeast two-hybrid system. The protein was found to be very unstable on the
      basis of urea- and guanidinium chloride-induced denaturation studies monitored by
      NMR and CD, respectively. Despite these unfavorable properties, total NMR
      assignments were accomplished with uniform 13C and 15N isotope labeling. All
      multidimensional NMR experiments were performed at a very low concentration of
      0.2 mM. The secondary structure was then determined from the NMR data. The
      results of NMR and CD studies indicate that the protein is highly alpha-helical,
      and the ankyrin repeat sequences show helix-turn-helix structures. This is the
      first structural information obtained for the important motif of ankyrin repeats.
      Overall, p16/delta 1-8 appears to be conformationally flexible. In order to
      understand the structural basis of the functional changes for some mutants
      existing in tumor cells, several missense mutants of p16/delta 1-8 were
      constructed. Four of them were expressed at high levels and purified. The
      molecular and structural properties of these mutants were analyzed by CD and NMR
      and compared with the corresponding properties of wild-type p16/delta 1-8. The
      results suggest that the functional changes in P114L and G101W are likely to be
      related to global conformational changes. In addition, we have demonstrated that
      the tendency of aggregation increases significantly by a single D84H mutation.

PMID- 8755728
TI  - Human ferredoxin: overproduction in Escherichia coli, reconstitution in vitro,
      and spectroscopic studies of iron-sulfur cluster ligand cysteine-to-serine
      mutants.
AB  - Human ferredoxin, the human equivalent of bovine adrenodoxin, is a small iron
      sulfur protein with one [2Fe-2S] cluster. It functions, as do other vertebrate
      ferredoxins, to transfer electrons during the processes of steroid hormone
      synthesis. A DNA fragment encoding the mature form of human ferredoxin was cloned
      into an expression vector under control of the T7 RNA polymerase/promoter system.
      The protein was overproduced in Escherichia coli, and the [2Fe-2S] cluster was
      incorporated into the protein by in vitro reconstitution. The overall yield was
      approximately 30 mg of purified, reconstituted ferredoxin per liter of culture.
      Four of the five cysteines in human ferredoxin are coordinated to the iron-sulfur
      cluster. First, the non-ligand cysteine (cysteine-95) was mutated to alanine, and
      then double mutants were created in which each of the other four cysteines (at
      positions 46, 52, 55, and 92) were mutated individually to serine. The wild-type
      ferredoxin and each of the five mutant proteins were studied by UV-visible
      spectroscopy and electron paramagnetic resonance spectroscopy. The EPR gav values
      of all five mutants were very similar to that of wild-type human ferredoxin. In
      the reduced state, three of the cysteine-to-serine mutants exhibited axial EPR
      spectra similar to that of wild-type, but one of the double mutants (C52S/C95A)
      exhibited a rhombic EPR spectrum. The UV-visible spectroscopic properties of the
      wild-type and the C95A mutant ferredoxins were identical, but those of the other
      cysteine-to-serine mutant proteins of human ferredoxin were quite different from
      those of the wild-type protein and each other. These results, along with those
      from cysteine-to-serine mutations in other ferredoxins, provide the basis for a
      more comprehensive theoretical and practical understanding of the features
      important to the ligation of [2Fe-2S] clusters, although they do not yet permit
      determination of which two cysteines ligate Fe(II) and which ligate Fe(III) in
      the reduced protein.

PMID- 8755729
TI  - Crystal structure of phosphatidylinositol-specific phospholipase C from Bacillus
      cereus in complex with glucosaminyl(alpha 1-->6)-D-myo-inositol, an essential
      fragment of GPI anchors.
AB  - Numerous proteins on the external surface of the plasma membrane are anchored by
      glycosylated derivatives of phosphatidylinositol (GPI), rather than by
      hydrophobic amino acids embedded in the phospholipid bilayer. These GPI anchors
      are cleaved by phosphatidylinositol-specific phospholipases C (PI-PLCs) to
      release a water-soluble protein with an exposed glycosylinositol moiety and
      diacylglycerol, which remains in the membrane. We have previously determined the
      crystal structure of Bacillus cereus PI-PLC, the enzyme which is widely used to
      release GPI-anchored proteins from membranes, as free enzyme and also in complex
      with myo-inositol [Heinz, D.W., Ryan, M. Bullock, T.L., & Griffith, O. H. (1995)
      EMBO J. 14, 3855-3863]. Here we report the refined 2.2 A crystal structure of
      this enzyme complexed with a segment of the core of all GPI anchors,
      glucosaminyl(alpha 1-->6)-D-myo-inositol [GlcN-(alpha 1-->6)Ins ]. The myo
      inositol moiety of GlcN(alpha 1-->6)Ins is well-defined and occupies essentially
      the same position in the active site as does free myo-inositol, which provides
      convincing evidence that the enzyme utilizes the same catalytic mechanism for
      cleavage of PI and GPI anchors. The myo-inositol moiety makes several specific
      hydrogen bonding interactions with active site residues. In contrast, the
      glucosamine moiety lies exposed to solvent at the entrance of the active site
      with minimal specific protein contacts. The glucosamine moiety is also less well
      defined, suggesting enhanced conformational flexibility. On the basis of the
      positioning of GlcN(alpha 1-->6)Ins in the active site, it is predicted that the
      remainder of the GPI-glycan makes little or no specific interactions with B.
      cereus PI-PLC. This explains why B. cereus PI-PLC can cleave GPI anchors having
      variable glycan structures.

PMID- 8755730
TI  - Three-dimensional solution structure and 13C nuclear magnetic resonance
      assignments of the colicin E9 immunity protein Im9.
AB  - The 86-amino acid colicin E9 immunity protein (Im9), which inhibits the DNase
      activity of colicin E9, has been overexpressed in Escherichia coli and
      isotopically enriched with 15N and 13C. Using the 3D CBCANH and CBCA(CO)NH
      experiments, we have almost completely assigned the backbone 13C resonances and
      extended previously reported 15N/1H backbone assignments [Osborne et al. (1994),
      Biochemistry 33, 12347-12355]. Side chain assignments for almost all residues
      were made using the 3D 13C HCCH-TOCSY experiment allied to previous 1H
      assignments. Sixty solution structures of Im9 were determined using the DIANA
      program on the basis of 1210 distance restraints and 56 dihedral angle
      restraints. The 30 lowest-energy structures were then subjected to a slow-cooling
      simulated annealing protocol using XPLOR and the 21 lowest-energy structures,
      satisfying the geometric restraints chosen for further analysis. The Im9
      structure is well-defined except for the termini and two solvent-exposed loops
      between residues 28-32 and 57-64. The average RMSD about the average structure of
      residues 4-84 was 0.94 A for all heavy atoms and 0.53 A for backbone C alpha, C =
      O, and N atoms. The Im9 fold is novel and can be considered a distorted
      antiparallel four-helix bundle, in which the third helix is rather short, being
      terminated close to its N-terminal end by a proline at its C-terminus. The
      structure fits in well with available kinetic and biochemical data concerning the
      interaction between Im9 and its target DNase. Important residues of Im9 that
      govern specificity are located on the molecular surface in a region rich in
      negatively charged groups, consistent with the proposed electrostatically steered
      association [Wallis et al. (1995a), Biochemistry 34, 13743-13750].

PMID- 8755731
TI  - Glycophorin as a receptor for Sendai virus.
AB  - Glycophorin A was reconstituted into large unilamellar vesicles of egg
      phosphatidylcholine by detergent dialysis. The observed overall rate of Sendai
      virus fusion increased approximately 4-fold between 0 and 0.006 mol %
      glycophorin, roughly proportional to the glycophorin content. However, no further
      increase in rate was observed at 0.02 mol % glycophorin. Treatment of reassembled
      glycophorin-liposomes with neuraminidase resulted in a significant decrease in
      the percent of viral fusion, confirming that the presence of sialic acid residues
      on glycophorin is essential for its role as a receptor. The sialic acid
      containing glycolipid, the ganglioside GD1a, was also incorporated into
      phosphatidylcholine liposomes, either in addition to or in place of glycophorin
      A. Comparing, on the basis of sialic acid content, liposomes containing either
      glycophorin or GD1a, comparable rates and extents of fusion were found. However,
      on a molar basis glycophorin is much more effective. It was found that the
      addition of GD1a to glycophorin-containing liposomes only slightly increased the
      rate of fusion. This was largely due to an increase in the percent of virions
      capable of fusing.

PMID- 8755732
TI  - Correlation of the phosphorylation states of pp60c-src with tyrosine kinase
      activity: the intramolecular pY530-SH2 complex retains significant activity if
      Y419 is phosphorylated.
AB  - Rapid digestion of pp60c-src tyrosine kinase (src TK) in combination with
      electrospray ionization mass spectrometry enabled the determination of the time
      course for autophosphorylation of three tyrosine sites (Y338, Y419, and Y530) and
      a correlation with src TK activity. A form of src TK was purified from
      baculovirus-infected cells which contains only Y338 partially phosphorylated.
      Incubation with MgATP increases the phosphorylation of all three sites. The
      autophosphorylation and dephosphorylation of Y419 are directly correlated with
      the level of src TK activity. The role of Y338 phosphorylation is unknown.
      Conditions resulting in complete autophosphorylation of Y530 were identified by
      electrospray ionization mass spectrometry. Surface plasmon resonance detection
      and size exclusion chromatography provide direct evidence for an intramolecular
      pY530-SH2 complex, supporting previous models [Matsuda, M., Mayer, B.J., Fukui,
      Y., & Hanafusa, H. (1990) Science 248, 1537-1539]. Contrary to these models, when
      the enzyme is fully phosphorylated on Y530, phosphorylated on Y419, and present
      only as the intramolecular pY530-SH2 complex, 20% of the kinase activity is
      retained. In addition, the k(m)'s for substrates are unaffected. Disruption of
      the pY530-SH2 interaction and activation of kinase activity by a high-affinity
      SH2 ligand yield a Kactivation which is 200-fold larger than the Kd for ligand
      binding to the uncomplexed src SH2 domain. These data suggest a Keq of 200
      (unitless) for the intramolecular association of pY530 with the SH2 domain. We
      propose that the pY530-SH2 interaction modulates signal transduction by down
      regulating src TK activity 5-fold, and perhaps more importantly by inhibiting
      protein-protein interactions with the SH2 domain. These results have significant
      implications relative to the development of SH2 ligands as therapeutics to
      control aberrant signal transduction. These ligands will be 200-fold less
      effective at inhibiting protein-protein interactions versus down-regulated src TK
      than versus activated src TK. This should minimize activation of src TK activity
      in normal cells and lead to an increased therapeutic index.

PMID- 8755733
TI  - Temperature dependence of polypeptide partitioning between water and phospholipid
      bilayers.
AB  - Various thermodynamic forces (e.g., the hydrophobic effect, electrostatic
      interactions, peptide immobilization, peptide conformational changes, "bilayer
      effects," and van der Waals dispersion forces) can participate in the transfer of
      polypeptides from aqueous solution into lipid bilayers. To investigate the
      contributions of these forces to peptide-membrane thermodynamics, we have studied
      the temperature dependence of the water-bilayer partitioning of 4 polypeptides
      derived from the first 25 amino acid residues in the presequence of subunit IV of
      yeast cytochrome c oxidase (Cox IVp) using electron paramagnetic resonance
      spectroscopy. The partitioning of the Cox IVp peptides into phospholipid bilayers
      increases as the temperature is increased from 3 to 40 degrees C. The
      contribution of bilayer surface expansion to the temperature-dependent
      partitioning is estimated to be relatively small and to contribute minimally to
      the increased bilayer binding of the peptides with increasing temperature.
      Thermodynamic analysis of the data shows that the transfer of the peptides from
      water into bilayers at 298 K is driven by the entropic term (-T delta Str) with
      values ranging from -6.7 to -10 kcal mol-1, opposed by the enthalpic term (delta
      Htr) by approximately 4 kcal mol-1, and accompanied by a change in heat capacity
      (delta Cp) ranging from -117 to -208 cal K-1 mol-1. Our results indicate that
      while a variety of forces do, in fact, contribute to the transfer free energies
      (delta Gtr), the major driving force for the water-to-bilayer transfer is the
      hydrophobic effect.

PMID- 8755734
TI  - Identification of significant residues in the substrate binding site of Bacillus
      stearothermophilus farnesyl diphosphate synthase.
AB  - Farnesyl diphosphate synthases have been shown to possess seven highly conserved
      regions (I-VII) in their amino acid sequences [Koyama et al. (1993) J. Biochem.
      (Tokyo) 113, 355-363]. Site-directed mutants of farnesyl diphosphate synthase
      from Bacillus stearothermophilus were made to evaluate the roles of the conserved
      aspartic acids in region VI and lysines in regions I, V, and VI. The aspartate at
      position 224 was changed to alanine or glutamate (mutants designated as D224A and
      D224E, respectively); aspartates at positions 225 and 228 were changed to
      isoleucine and alanine (D225I, D228A); lysine at position 238 was changed to
      either alanine or arginine (K238A, K238R). The lysines at positions 47 and 183
      were changed to isoleucine and alanine (K471, K183A), respectively. Kinetic
      analyses of the wild-type and mutant enzymes indicated that the mutagenesis of
      Asp-224 and Asp-225 resulted in a decrease of Kcat values of approximately 10(4)-
      to 10(5)-fold compared to the wild type. On the other hand, D228A showed a Kcat
      value approximately one-tenth of that of the wild type, and the k(m) value for
      isopentenyl diphosphate increased approximately 10-fold. Both K471 and K183A
      showed k(m) values for isopentenyl diphosphate 20-fold larger and kcat values 70
      fold smaller than the wild type. These results suggest that the two conserved
      lysines in regions I and V contribute to the binding of isopentenyl diphosphate
      and that the first and the second aspartates in region VI are involved in
      catalytic function. Aspartate-228 is also important for the binding of
      isopentenyl diphosphate rather than for catalytic reaction.

PMID- 8755735
TI  - Structural basis for ligand discrimination and response initiation in the heme
      based oxygen sensor FixL.
AB  - FixL is a multiple-domain bacterial O2-sensing protein that modulates the
      activity of its kinase domain in response to O2 concentration. The kinase
      activity is coupled, via phosphoryl transfer, to transcriptional activation by a
      response-regulating protein, FixJ. Heme ligation resulting in a transition from
      high to low spin inhibits the kinase through an, as yet, ill-defined mechanism.
      This report presents spectroscopic, kinetic, and thermodynamic data on various
      complexes of two deletion derivatives of Rhizobium meliloti FixL, FixLN (the heme
      domain) and a functional heme kinase, FixL*. Resonance Raman characterization of
      metFixLN and metFixL* indicates that the heme core is smaller than that observed
      in metmyoglobin and is indicative of a five-coordinate high-spin heme in
      metFixLs. Resonance Raman spectra of FixL-CO adducts reveal that the Fe-C = O
      unit and/or its electrostatic environment in FixL*-CO is distorted relative to
      that in FixLN-CO. The 1H NMR spectra of the met forms further support the model
      of an asymmetric perturbation of the heme pocket structure associated with the
      presence of the kinase domain in FixL*. Observation of equivalent Fe-imidazole
      stretching vibrations for deoxyFixLN and deoxyFixL* (212 cm-1) indicates that the
      source of this perturbation in the heme pocket of FixL* does not lie on the
      proximal side of the heme. The equivalent Fe-imidazole stretching frequencies for
      deoxyFixLN and FixL* indicate that the presence of the kinase domain does not
      alter the relative strength of the proximal Fe-imidazole bond and that the
      proximal imidazole ligand is weakly H-bonded, probably to a backbone carbonyl
      group. Kinetic and thermodynamic data for the reactions of cyanide and fluoride
      ions with FixL are consistent with shape selectivity due to steric and/or an
      anisotropic electrostatic field in the distal heme pocket being responsible for
      the unique reactivities (or lack thereof) of FixL with ligands, i.e., O2, CO, CN
      , F-, N3-, and SCN-. While the rate constants for binding of CN- to metFixLN and
      metFixL* are an order of magnitude slower than that for metMb, the stabilities of
      these complexes and metMb-CN are nearly the same. Neither N3- nor SCN- binds to
      the heme with measurable affinity. Since other ferric heme proteins form stable
      adducts with these ligands, the inability of FixL to form analogous complexes
      suggests that the ligand selectivity of this protein is rooted in insurmountable
      activation barriers to the binding of ligands containing more than two atoms and
      for ligands whose lowest-energy coordination geometries are linear. This allows
      the natural O2 ligand to compete kinetically with other naturally occurring
      ligands that form stable complexes with unencumbered hemes. Moreover, the rate
      constant for binding of CN- to the functional heme-kinase (metFixL*) is smaller
      than its metFixLN counterpart and the stability of metFixL*-CN is measurably
      lower than that of metFixLN-CN. This indicates that the contacts between the heme
      and kinase domains of FixL* impose more stringent geometric constraints on ligand
      binding than FixLN. The kinase is thus implicated in a possible mechanism for
      phosphate-dependent feedback control over ligand affinity of the heme.

PMID- 8755736
TI  - Proteolytic release of membrane-bound angiotensin-converting enzyme: role of the
      juxtamembrane stalk sequence.
AB  - Many structurally and functionally diverse membrane proteins are solubilized by a
      specific proteolytic cleavage in the stalk sequence adjacent to the membrane
      anchor, with release of the extracellular domain. Examples are the amyloid
      precursor protein, membrane-bound growth factors, and angiotensin-converting
      enzyme (ACE). The identities and characteristics of the responsible proteases
      remain elusive. We have studied this process in Chinese hamster ovary (CHO) cells
      stably expressing wild-type ACE (WT-ACE; human testis isozyme) or one of four
      juxtamembrane (stalk) mutants containing either deletions of 17, 24, and 47
      residues (ACE-JM delta 17, -JM delta 24, and -JM delta 47, respectively) or a
      substitution of 26 stalk residues with a 20-residue sequence from the stalk of
      the low-density lipoprotein receptor (ACE-JMLDL). The C termini of released,
      soluble WT-ACE and ACE-JM delta 17 and -JMLDL were determined by MALDI-TOF mass
      spectrometry analyses of C-terminal peptides generated by CNBr cleavage. Observed
      masses of 4264 (WT-ACE) and 4269 (ACE-JM delta 17) are in good agreement with an
      expected mass of 4262 for the C-terminal CNBr peptide ending at Arg-627,
      indicating cleavage at the Arg-627/Ser-628 bond in both WT-ACE and ACE-JM delta
      17, at distances of 24 and 10 residues from the membrane, respectively. Data for
      ACE-JM delta 24 are also consistent with cleavage at or near Arg-627. For ACE
      JMLDL, in which the native cleavage site is absent, observed masses of 4372 and
      4542 are in close agreement with expected masses of 4371 and 4542 for peptides
      ending at Ala-628 and Gly-630, respectively, indicating cleavages at 17 or 15
      residues from the membrane. These data indicate that the membrane-protein
      solubilizing protease (MPSP) in CHO cells is not constrained by a particular
      cleavage site motif or by a specific distance from the membrane but instead may
      position itself with respect to the putative proximal, folded extracellular
      domain adjacent to the stalk. Nevertheless, cleavage at a distance of 10 residues
      from the membrane is more favorable, as ACE-JM delta 17 is cleaved 12-fold faster
      than WT-ACE. In contrast, ACE-JM delta 24 is released 17-fold slower, suggesting
      that a minimum distance from the membrane must be preserved. This is supported by
      results with the ACE-JM delta 47 mutant, which is membrane-bound but not cleaved,
      likely because the entire stalk has been deleted. Finally, soluble full-length
      (anchor-plus) WT-ACE is not cleaved when incubated with various CHO cell
      fractions or intact CHO cells. On the basis of these and other data, we propose
      that the CHO cell MPSP that solubilizes ACE (1) only cleaves proteins embedded in
      a membrane; (2) requires an accessible stalk and cleaves at a minimum distance
      from both the membrane and proximal extracellular domain; (3) positions itself
      primarily with respect to the proximal extracellular domain; and (4) may have a
      weak preference for cleavage at Arg/Lys-X bonds.

PMID- 8755737
TI  - Assignment of free and disulfide-bonded cysteine residues in testis angiotensin
      converting enzyme: functional implications.
AB  - Human testicular angiotensin-converting enzyme (tACE) is an extracellular protein
      that contains seven cysteine residues. The cysteines occur in a sequential
      distribution that is precisely mimicked in the tACE from rabbit and mouse, and in
      both domains of all known species of somatic ACE. One of the cysteines in human
      tACE, Cys496, is present in the reduced form as shown by labeling it with 5-[[2
      (iodoacetyl)amino]ethylamino]naphthalene-1-sulfonic acid, isolating the
      fluorescent peptide from enzymatic digests by HPLC, and analyzing its sequence by
      matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS). Thiol
      reagents have no significant effect on the activity of tACE, indicating that this
      Cys is not involved in catalysis. The other six cysteines exist as three
      disulfides. Mass spectral analysis of cyanogen bromide peptides has established
      that the cystine connectivities follow a nearest-neighbor, aabbcc, pattern i.e.,
      Cys152-Cys158, Cys352-Cys370, and Cys538-Cys550, in which the disulfides form
      three small loops of five, 17, and 11 residues, respectively. Although these
      disulfide loops constitute less than 5% of the total sequence of the protein,
      they contribute to the overall structural stabilization of tACE.

PMID- 8755738
TI  - Active-site structure analysis of recombinant human inducible nitric oxide
      synthase using imidazole.
AB  - Nitric oxide synthase catalyzes the pyridine nucleotide-dependent oxidation of L
      arginine to nitric oxide and L-citrulline. It is a specialized cytochrome P450
      monooxygenase that is sensitive to inhibition by imidazole. Steady-state kinetic
      studies on recombinant human inducible nitric oxide synthase (rH-iNOS)
      demonstrate that imidazole and 1-phenylimidazole are competitive and reversible
      inhibitors versus L-arginine. Structure-activity relationship and pH dependence
      studies on the inhibition suggest that the neutral form of imidazole may be the
      preferred species and that the only modifications allowed without the loss of
      inhibition are at the N-1 position of imidazole. Optical spectrophotometric
      studies of rH-iNOS with imidazole and 1-phenylimidazole yielded type II
      difference spectra exhibiting Kd values of 63 +/- 2 and 28 +/- 3 microM,
      respectively. These values were in good agreement with the steady-state Ki of 95
      +/- 10 and 38 +/- 4 microM, respectively, and confirms the site of binding is at
      the sixth axial ligand of the heme. Imidazole (2.2 mM) also perturbed the Kd of L
      arginine from 3.03 +/- 0.45 to 209 +/- 10 microM. The observed increase in the Kd
      for L-arginine is consistent with imidazole being a competitive inhibitor versus
      L-arginine. The IC50 values of imidazole and 1-phenylimidazole were lower in the
      absence of exogenous BH4, and both inhibitors also competitively inhibited the
      BH4-dependent activation of the enzyme. These data taken together suggest that
      the L-arginine, dioxygen, and the BH4 binding sites are in close proximity in rH
      iNOS. Furthermore, these studies demonstrate the usefulness of imidazole
      compounds as active site probes for recombinant human iNOS.

PMID- 8755739
TI  - Fatty acids and anionic phospholipids alter the palmitoyl coenzyme A kinetics of
      hepatic monoacylglycerol acyltransferase in Triton X-100 mixed micelles.
AB  - In order to gain a better understanding of the kinetics of activation and
      inhibition of hepatic monoacylglycerol acyltransferase (MGAT) (EC 2.3.1.22) by
      fatty acid, we examined the effect of fatty acid with respect to MGAT's long
      chain acyl-CoA substrate in Triton X-100 mixed micelles. At concentrations
      between 2.5 and 5.3 mol %, oleic acid stimulated MGAT activity 2-fold, whereas
      oleic acid inhibited MGAT at concentrations higher than 7.5 mol %. The dependence
      on palmitoyl-CoA was highly cooperative with a Hill constant of greater than 2.4.
      When present at less than 3 mol%, oleic acid eliminated the lag in the dependence
      curve. When concentrations of oleic acid were higher than 3 mol %, Michaelis
      Menton kinetics were observed with an apparent k(m) value of about 54 microM for
      palmitoyl-CoA but with progressively decreasing Vmax values. This effect was not
      observed with octanoic acid, suggesting that the medium-chain fatty acid is
      unable to associate stably with the mixed micelle and, thus, cannot substantially
      alter substrate affinity. When anionic phospholipids were tested, phosphatidic
      acid, lysophosphatidic acid, phosphatidylserine, and phosphatidylinositol
      eliminated some of the lag in activation by palmitoyl-CoA. At high molar
      concentrations of the anionic lipid activators, apparent k(m) values ranged from
      77 microM for phosphatidic acid to 196 microM for phosphatidylinositol.
      Zwitterionic phospholipids had no effect, nor did the non-phospholipid activators
      bovine serum albumin or sn-1,2-diacylglycerol. CaCl2, but not neomycin or KC1,
      could overcome the inhibitory effect of oleic acid; thus, the inhibitory effect
      of fatty acid did not appear to occur by electrostatic interactions. These
      blockers did not change the effects observed with the anionic phospholipid
      activators or with the inhibitor, sphingosine. An altered k(m) for palmitoyl-CoA
      in the presence of fatty acid or anionic phospholipid suggests that both long
      chain fatty acids and phospholipid cofactors may induce a conformational change
      in MGAT, thereby altering the enzyme's affinity for its long-chain acyl-CoA
      substrate. These data further support the hypothesis that the synthesis of
      glycerolipids via the monoacylglycerol pathway may be highly regulated via a
      variety of lipid second messengers such as phosphatidic acid and diacylglycerol,
      as well as by the influx of fatty acids derived from high-fat diets, or from the
      hydrolysis of adipocyte triacylglycerol during fasting or diabetes.

PMID- 8755740
TI  - Functional interaction of the c-Myc transactivation domain with the TATA binding
      protein: evidence for an induced fit model of transactivation domain folding.
AB  - c-Myc is a member of a family of sequence specific-DNA binding proteins that are
      thought to regulate the transcription of genes involved in normal cell growth,
      differentiation, and apoptosis. In order to understand how human c-myc functions
      as a transcription factor, we have studied the mechanism of action and structure
      of the N-terminal transactivation domain, amino acids 1-143. In a protein
      interaction assay, c-myc1-143 bound selectively to two basal transcription
      factors, the TATA binding protein (TBP) and the RAP74 subunit of TFIIF.
      Furthermore, the isolated c-myc transactivation domain competed for limiting
      factors required for the assembly of a functional preinitiation complex. This
      squelching of basal transcription was reversed in a dose-dependent manner by
      recombinant TBP. Taken together, these results identify TBP as an important
      target for the c-myc transactivation domain, during transcriptional initiation.
      Similar to other transactivation domains, the c-myc1-143 polypeptide showed
      little or no evidence of secondary structure, when measured by circular dichroism
      spectroscopy (CD) in aqueous solution. However, significant alpha-helical
      conformation was observed in the presence of the hydrophobic solvent
      trifluoroethanol. Strikingly, addition of TBP caused changes in the CD spectra
      consistent with induction of protein conformation in c-myc1-143 during
      interaction with the target factor. This change was specific for TBP as a similar
      effect was not observed in the presence of TFIIB. These data support a model in
      which target factors induce or stabilize a structural conformation in activator
      proteins during transcriptional transactivation.

PMID- 8755741
TI  - Sequence preference of 7,12-dimethylbenz[a]anthracene-syn-diol epoxide-DNA
      binding in the mouse H-ras gene detected by UvrABC nucleases.
AB  - We have found that 7,12-dimethylbenz[a]anthracene-syn-diol epoxide (syn-DMBADE)
      modified DNA fragments are sensitive to UvrABC incision. The incisions occur
      mainly seven bases 5' and four bases 3' of a syn-DMBADE-modified adenine or
      guanine residue. The kinetics of UvrABC incision at different sequences in a DNA
      fragment are the same, and the extent of UvrABC incision is proportional to the
      syn-DMBADE concentration. On the basis of these results, we have concluded that
      UvrABC incision on syn-DMBADE-DNA adducts is independent of DNA sequence and is
      quantitative. Using the UvrABC incision method, we have analyzed the syn-DMBADE
      DNA binding spectrum in several defined DNA fragments, including the first two
      exons of the mouse H-ras gene. We have found that both guanine and adenine
      residues in codons 12, 13, and 61 of the H-ras gene are strong syn-DMBADE binding
      sites. These results suggest that the initial binding of DMBADE may greatly
      contribute to the frequency of H-ras mutations. Results from dinucleotide binding
      analysis indicate that the 5'-nearest neighbor displays a greater effect on syn
      DMBADE-DNA binding than the 3'-nearest neighbor.

PMID- 8755742
TI  - Raman spectroscopy of the Ff gene V protein and complexes with poly(dA):
      nonspecific DNA recognition and binding.
AB  - Raman spectra of crystals and solutions of the single-stranded DNA binding
      protein of bacteriophage Ff (gene V protein, gVp) and of solution complexes of
      gVp with single-stranded poly-(deoxyadenylic acid) [poly(dA)] reveal the
      following: (i) The gVp secondary and tertiary structures are similar in solution
      and in the crystal and are dominated by beta-sheet domains, in agreement with NMR
      and X-ray findings. (ii) Subunit conformation and side chain environments of gVp
      are virtually unchanged over a wide range of salt concentration (0 < [NaCl] < 100
      mM); however, the solution conformation of poly(dA) exhibits sensitivity to added
      salt. The perturbed Raman markers indicate subtle changes in helix backbone
      geometry with accompanying small differences in base stacking as the
      concentration of NaCl is changed. (iii) In complexes with poly(dA), neither the
      conformation of gVp nor its side chain environments are altered significantly in
      comparison to the free protein. This is the case at both high salt (nucleotide-to
      subunit binding stoichiometry n = 4) and low salt (n = 3). (iv) The Raman
      signature of poly(dA) undergoes small perturbations upon gVp binding, indicative
      of small changes in base stacking and phosphodiester backbone conformation. The
      present results show that the different stoichiometric binding modes of gVp to
      poly(dA) are accomplished without significant changes in gVp subunit structure
      and with only modest changes in the single-stranded poly(dA) ligand. This
      contrasts sharply with sequence-specific double-stranded DNA binding proteins,
      such as the phage lambda and D108 repressors, which undergo substantial
      structural changes upon DNA binding, and which also alter more dramatically the
      Raman fingerprints of their DNA target sites. Thus, nonspecific and specific
      nucleic acid recognition modes are distinguishable by Raman spectroscopy. The
      Raman signature of gVp also allows examination of hydrogen bonding interactions
      of unique side chains within the hydrophobic core (cysteine 33) and at the
      binding interface (tyrosine 41). These are discussed in relation to the recently
      published gVp crystal structure.

PMID- 8755743
TI  - Evidence for the interaction of avian 3-hydroxy-3-methylglutaryl-CoA synthase
      histidine 264 with acetoacetyl-CoA.
AB  - Previous work on HMG-CoA synthase has implied the presence of a reactive active
      site histidine, prompting our examination of the possible function of invariant
      histidine residues by site-directed mutagenesis. Mutations encoding H197N,
      H264N/A, and H436N HMG-CoA synthases were constructed, and the mutant enzymes
      were overexpressed in Escherichia coli BL21(DE3). Kinetic characterization of the
      isolated synthase variants indicates that, while H197N and H436N enzymes behave
      similarly to wild-type synthase, H264N and H264A synthases exhibit significant
      differences. Although the k(m) for acetyl-CoA is not substantially altered,
      H264N/A synthases catalyze production of HMG-CoA at a diminished (approximately
      25-fold slower) rate. In contrast, H264N/A synthases can efficiently catalyze the
      acetyl-CoA hydrolysis partial reaction exhibiting a k(m) for acetyl-CoA that,
      again, approximates the value obtained with the wild-type enzyme. These mutants
      also retain the ability to form significant levels of the acetyl-S-enzyme
      reaction intermediate. The functional catalysis of partial reactions argues that
      the H264 mutant proteins retain substantial structural integrity. In this
      context, it appears significant that the H264N/A synthases exhibit a
      approximately 100-fold increase in the k(m) for acetoacetyl-CoA. In order to test
      whether the two orders of magnitude effect may be largely attributed to a
      decreased affinity of acetoacetyl-CoA for these enzymes and, more specifically,
      whether H264 interacts with the carbonyl oxygen of acetoacetyl-CoA's thioester,
      turnover of S-(3-oxobutyl)-CoA, a thioether analog of acetoacetyl-CoA, was
      investigated. This alternative substrate, in which a methylene group replaces the
      thioester carbonyl, is utilized by wild-type synthase with an apparent Vmax that
      is approximately 100-fold lower and an apparent k(m) that is 25-fold higher than
      the values obtained using the physiological substrate, acetoacetyl-CoA. H264A
      synthase also catalyzes the turnover of S-(3-oxobutyl)-CoA; the diminution in
      rate supported by the alternative substrate is comparable in magnitude to the
      effect observed for wild-type enzyme. In contrast, H264A exhibits comparable
      apparent k(m) values for S-(3-oxobutyl)-CoA and acetoacetyl-CoA. Thus, unlike
      wild-type synthase, there is no penalty in terms of efficiency of H264A
      saturation when the alternative thioether substrate replaces the physiological
      substrate. These data suggest that the imidazole of H264 in avian enzyme may play
      a role in anchoring the second substrate, acetoacetyl-CoA, by interacting with
      the carbonyl oxygen of the thioester functionality.

PMID- 8755744
TI  - Covalent binding of three epoxyalkyl xylosides to the active site of endo-1,4
      xylanase II from Trichoderma reesei.
AB  - The three-dimensional structures of endo-1,4-xylanase II (XYNII) from Trichoderma
      reesei complexed with 4,5-epoxypentyl beta-D-xyloside (X-O-C5),3,4-epoxybutyl
      beta-D-xyloside (X-O-C4), and 2,3-epoxypropyl beta-D-xyloside (X-O-C3) were
      determined by X-ray crystallography. High-resolution measurement revealed clear
      electron densities for each ligand. Both X-O-C5 and X-O-C3 were found to form a
      covalent bond with the putative nucleophile Glu86. Unexpectedly, X-O-C4 was found
      to bind to the putative acid/base catalyst Glu177. In all three complexes, clear
      conformational changes were found in XYNII compared to the native structure.
      These changes were largest in the X-O-C3 complex structure.

PMID- 8755745
TI  - Histidine-450 is the catalytic residue of L-3-hydroxyacyl coenzyme A
      dehydrogenase associated with the large alpha-subunit of the multienzyme complex
      of fatty acid oxidation from Escherichia coli.
AB  - Multienzyme complexes of fatty acid oxidation from Escherichia coli with Gln or
      Ala substituting for His450 or with Ala in place of Gly322 in the large alpha
      subunit have been purified and characterized. The alpha/Gly322-->Ala mutation did
      not significantly affect the catalytic efficiencies (kcat/k(m)) of different
      component enzymes except for a 6.1-fold decrease in the kcat/k(m) of L-3
      hydroxyacyl-CoA dehydrogenase and a 10-fold increase in the k(m) for NADH. This
      observation confirms the prediction [Yang, X.-Y. H., Schulz, H., Elzinga, M., &
      Yang, S.-Y. (1991) Biochemistry 30, 6788-6795] that the E. coli dehydrogenase has
      an NAD-binding site at its amino-terminal domain and structurally resembles the
      pig heart dehydrogenase. The pH dependence of the kcat/k(m) of the E. coli
      dehydrogenase suggested the catalytic involvement of an amino acid residue with a
      pKa of 6, which is presumably a histidine residue as proposed previously on the
      basis of chemical modifications. Since His450 of the E. coli multifunctional
      protein is the only histidine conserved in all known L-3-hydroxyacyl-CoA
      dehydrogenases, and since its counterpart in pig heart enzyme appeared to be
      close to the 3-keto group of the fatty acyl moiety of the substrate, His450 was
      replaced by either Gln or Ala. The catalytic properties of 3-ketoacyl-CoA
      thiolase, enoyl-CoA hydratase, and delta 3-cis-delta 2-trans-enoyl-CoA isomerase
      of the alpha/His450-->Gln mutant complex were virtually unchanged except for a
      small decrease in the kcat values of the latter two enzymes. In contrast, the
      dehydrogenase of this mutant complex was almost inactive due to a greater than
      3000-fold decrease in its kcat and a 6-fold increase in the k(m) for NADH. The
      alpha/His450-->Ala mutant complex showed similar catalytic behaviors. Taken
      together, several lines of evidence lead to the conclusion that His450 is the
      catalytic residue of L-3-hydroxyacyl-CoA dehydrogenase of the E. coli
      multifunctional fatty acid oxidation protein.

PMID- 8755746
TI  - Management and outcome of posttraumatic syringomyelia.
AB  - Traumatic paraplegia is the most common cause of nonhindbrain-related
      syringomyelia. Fifty-seven patients with a mean age of 34.3 years at presentation
      were treated at the Midland Centre for Neurosurgery and Neurology between 1973
      and 1993. A variety of treatment strategies have been used over the years,
      including syringosubarachnoid and syringopleural shunts, spinal cord transection,
      and pedicled omental graft transposition. More recently decompressive
      laminectomy, subarachnoid space reconstruction and formation of surgical
      meningocele have been used. A total of 81 operations were performed in these
      patients, 69 of them at the Syringomyelia Clinic. Combinations of strategies were
      often chosen; the use of one strategy such as drainage did not preclude another
      such as transection or augmentation of the cerebrospinal fluid pathways. The
      overall postoperative complication rate was 12%. Problems specific to the
      operation type included dislodged, blocked, and infected drains (10 patients).
      Acute gastric dilation was seen following pedicled omental graft (one patient).
      At 6 years only 49% of the drains inserted still functioned. A higher than
      expected rate of cervical spondylotic myelopathy has been noted. Two patients
      developed Charcot's joints. Thirty-six patients were asked to score themselves
      with regard to limb function and performance of daily living activities and 30%
      reported improvement, particularly ion arm function. Since the use of magnetic
      resonance imaging has become widespread, it has become apparent that
      decompressive laminectomy with subarachnoid space reconstruction is effective in
      controlling the syrinx cavity. In complete paraplegia, spinal cord transection is
      an effective alternative. Pedicled omental grafting was associated with poor
      outcome and an increased complication rate and has been abandoned.

PMID- 8755747
TI  - Anterior cervical interbody fusion using autogeneic and allogeneic bone graft
      substrate: a prospective comparative analysis.
AB  - The authors conducted a prospective study of 132 patients requiring interbody
      fusion without instrumentation following anterior cervical discectomy to compare
      the efficacy of tricortical iliac crest allograft versus autograft fusion
      substrates. The objectives of the study were to assess the potential differences
      in interspace collapse, angulation, maintenance of cervical alignment and
      lordosis, and clinical and radiographic fusion success rates between the two
      fusion substrates. The impact of habitual cigarette smoking on fusion rates was
      also examined. Autograft tricortical iliac crest bone was found to be superior to
      allograft bone as an interbody fusion substrate after both single- and multiple
      level anterior cervical decompression procedures with respect to maintenance of
      cervical interspace height, interspace angulation, and radiographic and clinical
      fusion success rates. Cigarette consumption had a significant adverse effect on
      successful anterior cervical interbody fusion for both autograft and allograft
      substrate, an effect that was most pronounced among smokers treated with
      allograft bone (p = 0.004).

PMID- 8755748
TI  - Single-stage posterior vertebrectomy and replacement combined with posterior
      instrumentation for spinal metastasis.
AB  - The authors present a series of 25 patients who underwent single-stage complete
      spondylectomy, vertebral body reconstruction, and posterior segmental spinal
      stabilization for malignant metastatic disease involving multiple columns of the
      thoracolumbar spine. Patients were selected for this approach primarily because
      they were poor candidates for a transcavitary or lateral extracavitary approach
      or because the tumor involved both anterior and posterior columns of the spine.
      The operative approach used combines radical local resection of tumor via a
      bilateral transpedicular route, methylmethacrylate vertebral body reconstruction,
      and Luque rectangle stabilization in a single operation. Following surgery, the
      majority of patients experienced improvement in their neurological status,
      reduction in pain, or both. Most patients were functionally improved, or at least
      no worse, and spinal alignment was maintained in all. There was one local
      recurrence in a long-term survivor. Complications included cerebrospinal fluid
      fistulas, migrating graft material, and wound healing problems. The authors
      conclude that this surgical approach is safe and feasible for the radical
      resection of vertebral metastasis when combined with reconstruction and
      stabilization. This technique represents a useful alternative to other commonly
      used surgical approaches for the treatment of spinal metastases, and it should
      aid surgeons in selecting the optimum approach for individual patients.

PMID- 8755749
TI  - The anatomical suitability of the C1-2 complex for transarticular screw fixation.
AB  - Posterior transarticular screw fixation of the C1-2 complex has become an
      accepted method of rigid internal fixation for patients requiring posterior C1-2
      fusion. The principal limitation of this procedure is the location of the
      vertebral artery, because an anomalous position may prohibit screw placement. In
      this study, a consecutive series of computerized tomography (CT) scans was
      reviewed, and the suitability of each patient for transarticular screw fixation
      was evaluated. All of the fine-slice axial C1-2 CT scans and reconstructions
      performed on a spiral scanner over 2 years were reviewed. A novel screw
      trajectory reconstruction was designed to visualize the potential path of a
      transarticular screw in the plane of the reconstruction. Scans were reviewed for
      bone anatomy and the position of the transverse foramen. Seventeen (18%) of 94
      patients had a high-riding transverse foramen on at least one side of the C-2
      vertebra that would prohibit the placement of transarticular screws. The left
      side was involved in nine patients and the right in five. Three patients had
      bilateral anomalies. The mean age of the group with anomalies (35.9 years, range
      10-76) was not significantly different from the overall mean age (35.7 years,
      range 6-94). An additional five patients (5%) were considered to have anatomy in
      which screw placement was feasible but risky. On the basis of these data, it is
      postulated that 18% to 23% of patients may not be suitable candidates for
      posterior C1-2 transarticular screw fixation on at least one side.

PMID- 8755750
TI  - The surgical treatment of metastatic spinal tumors within the intradural
      extramedullary compartment.
AB  - The authors retrospectively reviewed the surgical outcomes in 10 cases of
      symptomatic intradural extramedullary spinal metastases of nonneurogenic origin
      because the collective experience in treating this rare manifestation of systemic
      cancer is limited. Pain and weakness were the presenting complaints in 70% of the
      patients and sensory changes were found in all cases. Cytological tests on one
      specimen of cerebrospinal fluid (CSF) from each of seven patients showed
      malignant cells in two cases. Gadolinium contrast-enhanced biplanar magnetic
      resonance (MR) imaging was effective in localizing the lesion and showed evidence
      of leptomeningeal carcinomatosis in two cases; myelography showed leptomeningeal
      carcinomatosis in one case and erroneously identified the lesion as
      intramedullary in the other. Eight of 10 cases had antecedent intracranial
      metastatic foci with the interval from presentation of the intracranial lesion to
      appearance of the spinal disease ranging from 3 to 51 months. The majority of the
      spinal lesions occurred in the thoracolumbar area. The most frequent histological
      type was adenocarcinoma and the most frequent source was the lung. In all cases
      laminectomies, intradural exploration, and biopsy or subtotal excision aided by
      microscopy and ultrasonography were performed. Results of surgical decompression
      were poor with only 30% of the patients showing improvement, at a 20% risk of
      perioperative mortality and a 60% risk of morbidity. Plans for surgical
      intervention in patients with intradural extramedullary metastases from a distant
      noneurogenic source should be weighed against the high association with
      intracranial lesions, overall poor prognosis, and modest symptomatic results of
      decompression. Comprehensive evaluation including multiple specimens of CSF for
      cytology and contrast-enhanced MR imaging should be undertaken to exclude
      patients with diffuse leptomeningeal involvement, who should be treated by means
      other than surgery.

PMID- 8755751
TI  - Postchemonucleolysis discectomy versus repeat discectomy: a prospective 1- to 13
      year comparison.
AB  - This long-term prospective study evaluates the clinical results of subsequent
      laminectomy in 103 consecutive patients who initially underwent chemonucleolysis
      (CNL) or laminectomy for lumbar disc herniation. Between 1981 and 1994, 53
      patients who had received CNL initially and then underwent laminectomy and 50
      patients treated initially with laminectomy underwent a repeat laminectomy.
      Clinical assessment at 6 weeks showed a success rate of 80.8% for post-CNL
      laminectomy and 78% for repeat laminectomy. At 6 months, the success rate for
      patients treated with CNL was 86% versus 78.7% for laminectomy. At 12 months, the
      overall success rate for the CNL group was 80.4% versus 83.3% for the laminectomy
      group, but in patients who had not obtained relief from the first procedure the
      success rate for the second procedure was higher for the post-CNL patients. A
      questionnaire was sent to all patients for 1- to 13-year follow-up review. The
      average follow-up period was 6.6 years for post-CNL laminectomy and 5.2 years for
      repeat laminectomy. The long-term success rate (81.8%) was higher in the post-CNL
      group compared to 64.4% in the repeat laminectomy group. Seven patients in the
      post-CNL group and nine in the repeat laminectomy group had undergone a third
      operation. When these originally successfully treated patients were reassigned
      after unsuccessful outcomes, the success rate for the CNL groups was 72.7%,
      versus 51.1% in the laminectomy group (p = 0.049). Employment rates were 80% for
      patients with CNL (21.8% changed jobs) and 76.3% for patients undergoing
      laminectomy (48.3% changed jobs) (p = 0.036). In conclusion, patients who
      underwent laminectomies after receiving CNL had significantly better long-term
      results than those who had repeat laminectomies.

PMID- 8755752
TI  - Surgical outcome after repeated transsphenoidal surgery in acromegaly.
AB  - Transsphenoidal selective adenomectomy is the most efficient primary treatment
      for acromegaly. However, management of persistent or recurrent disease remains
      controversial. The objective of the present study was to evaluate the early and
      long-term efficacy and safety of a second transsphenoidal surgery performed in
      those cases. The results of a retrospective study of 16 patients undergoing
      reoperation by the senior author (J.H.) between 1970 and 1991 are reported.
      Reoperation was performed for persistent or progressive acromegaly in 11
      patients, visual impairment in four, and disease recurrence in one. Normalization
      of growth hormone (GH) was defined as a basal GH level of less than 5
      micrograms/L and suppression to less than 2 micrograms/L during the oral glucose
      tolerance test. Long-term follow-up data were available in 15 patients. The
      second transsphenoidal surgery induced a greater than 50% decrease of GH level in
      11 patients. Three (19%) of 16 patients were cured according to the authors'
      criteria and remained so after 2, 7, and 20 years. Two more patients had a
      postoperative basal GH level of less than 5 micrograms/L but incomplete
      suppression during the oral glucose tolerance test. Thus, a total of five
      patients (31%) achieved a basal GH of less than 5 micrograms/L. One other patient
      who had no initial improvement after the second transphenoidal surgery had
      spontaneous normalization of his GH level after 13 years. The following
      complications of the second surgery occurred in three patients: one subarachnoid
      hemorrhage, two new visual field defects, one cranial nerve palsy, and one
      meningitis. Moreover, 10 patients (62.5%) developed one or more new pituitary
      hormone deficiencies. In conclusion, reoperation for persistent or recurrent
      acromegaly has low success and high complication rates. According to the authors'
      experience, this procedure should be reserved for patients unresponsive to other
      forms of therapy or with progressive visual impairment despite medical therapy.

PMID- 8755753
TI  - Perfluorocarbons: recent developments and implications for neurosurgery.
AB  - Over the last 30 years, perfluorocarbons (PFCs) have been extensively
      investigated as oxygen carriers. Early studies indicated that these compounds
      could be used as blood substitutes or protective agents against ischemia. Adverse
      characteristics such as instability, short intravascular half-life, and
      uncertainties concerning possible toxicity precluded wide clinical application.
      However, advances in PFC technology have led to the development of improved
      second-generation oxygen carriers that incorporate well-tolerated emulsifiers
      (egg-yolk phospholipids). The authors review recent developments in this field
      and consider the potential role of PFCs in future neurosurgical practice.
      Diagnostic applications could include their use to assess cerebral blood flow,
      local oxygen tension, and brain metabolism or to achieve enhanced imaging and
      precise staging of inflammatory, neoplastic, or vascular disease processes by
      means of computerized tomography, ultrasonography, and magnetic resonance
      studies. Therapeutic applications could include cerebral protection, an
      adjunctive role in radiotherapy of malignant brain tumors, protection against air
      embolism, the preservation of organs for transplantation, and ventilatory support
      in head-injured patients with compromised lung function. In addition, PFCs have
      been used successfully as a tool in ophthalmic microsurgery and potentially they
      could fulfill a similar role in microneurosurgery.

PMID- 8755754
TI  - Differentiation of receptive fields in the sensory cortex following stimulation
      of various nerves of the lower limb in humans: a magnetoencephalographic study.
AB  - The authors investigated magnetoencephalography following stimulation of the
      posterior tibial (PT) and sural (SU) nerves at the ankle, the peroneal nerve (PE)
      at the knee, and the femoral nerve (FE) overlying the inguinal ligament in seven
      normal subjects (14 limbs) and confirmed its usefulness in clarifying the
      detailed differentiation of the receptive fields in the lower limb area of the
      primary sensory cortex in humans. The results were summarized as follows: 1) the
      equivalent current dipoles (ECDs) estimated by the magnetic fields following
      stimulation of the PT and SU were located very close to each other, along the
      interhemispheric fissure in all 14 limbs. They were directed horizontally to the
      hemisphere ipsilateral to the stimulated nerve. 2) The ECD following stimulation
      of the FE was clearly different from that seen in the other nerves, in terms of
      the location and/or direction, in all 14 limbs. The ECDs of 14 limbs were
      classified into two types according to the distance of ECD location between PT
      and FE; Type 1 (> 1 cm, nine limbs) and Type 2 (< 1 cm, five limbs). The ECD
      following FE stimulation was located on the crown of the postcentral gyrus or at
      the edge of the interhemispheric fissure in Type 1 and was close to the ECDs
      following PT and SU stimulation along the interhemispheric fissure in Type 2. 3)
      The ECD following PE stimulation was located along the interhemispheric fissure
      in all 14 limbs as for PT and SU. Its location was slightly but significantly
      higher than that of PT and SU in Type 1 and was close to ECDs following PT and SU
      stimulation in Type 2. The present findings indicated that approximately 65%
      (nine of 14) of the limbs showed the particular receptive fields compatible with
      the homunculus. Large inter- and the intraindividual (left-right) differences
      found in the present study indicated a significant anatomical variation in the
      area of the lower limb in the sensory cortex of humans.

PMID- 8755755
TI  - Intrinsic tumors of the insula: a prospective surgical study of 30 patients.
AB  - Intrinsic insular tumors are frequently excluded from surgical treatment. The
      authors propose a more extensive approach to these lesions based on the results
      of this prospective series. From September 1993 to January 1995, 30 patients (18
      males and 12 females; mean age 42 years) harboring benign (15 patients) or
      malignant (15 patients) tumors involving the insula underwent surgical treatment.
      The dominant and nondominant hemispheres were both affected in 15 cases. Two
      groups were defined on the basis of preoperative magnetic resonance (MR) imaging:
      14 lesions were restricted to the insula and the corresponding opercula; the
      other 16 lesions also involved other mesocortical and/or allocortical areas. Most
      patients displayed only mild preoperative symptoms. The median score according to
      the Karnofsky performance scale was 90. Microsurgical removal was achieved via a
      transsylvian approach in nine cases and via a frontal and/or temporal approach in
      21 cases. According to early postoperative MR imaging, complete tumor removal
      (100%) was seen in five patients, nearly complete (> 80%) in 21, and incomplete
      resection (50%-80%) in four patients. There was no operative mortality; 19
      patients (63%) experienced immediate postoperative morbidity, including reduced
      performance. After a mean follow-up review of 8.5 months two of 21 patients
      suffered permanent deficits, accounting for an overall operative morbidity of
      10%. At the mean time of review, three patients with Grade IV tumors had died of
      tumor recurrence. The authors conclude that low-grade intrinsic insular tumors,
      as well as Grade III tumors, can be removed with favorable results in the
      majority of patients. Surgery to excise glioblastomas should only be considered
      for patients with good preoperative performance and young age.

PMID- 8755756
TI  - A novel computer-assisted volumetric stereotactic approach for resecting tumors
      of the posterior parahippocampal gyrus.
AB  - The authors report their experience using a novel surgical approach for resecting
      tumors located in the posterior parahippocampal gyrus. Prior attempts to resect
      epileptogenic foci in this location have been limited by a significant risk of
      injury to lateral temporal lobe cortical and vascular structures. To avoid these
      potential complications, the authors have used a lateral occipitosubtemporal,
      computer-assisted stereotactic volumetric approach to resect radiographically
      defined tumors in seven patients with intraaxial neoplasms of the posteromedial
      temporal lobe. This series included one female and six male patients, ranging in
      age from 15 to 67 years, who presented with seizures, visual field loss, or
      headache. Gross-total resection of three high-grade gliomas, two gangliogliomas,
      and one mixed glioma was accomplished with no permanent morbidity or operative
      mortality. The authors conclude that this approach is advantageous for resecting
      tumors in this location because, by avoiding unnecessary brain resection or
      retraction, it significantly reduces the risk of injury to lateral temporal lobe
      structures, helps maintain precise spatial and anatomical orientation for the
      surgeon, and, like all computer-assisted volumetric approaches, delineates the
      margin between the tumor and surrounding neural tissue.

PMID- 8755757
TI  - Functional stereotactic surgery for hemiballism.
AB  - The symptomatic and functional outcomes of a series of 14 patients with disabling
      and medically refractory hemiballism who were treated with functional
      stereotactic surgery are reported. Seven (50%) of the 14 patients had concomitant
      hemichorea. To relieve the hyperkinesia, the 14 patients underwent a total of 15
      stereotactic operations (one patient had a second stereotactic procedure).
      Combined lesions in the contralateral zona incerta and the base of the
      ventrolateral (oroventral) thalamus were applied in 13 instances. The zona
      incerta was reached by means of a movable chord electrode to obviate the need for
      repeated puncture. In two instances the medial pallidum was used as the
      stereotactic target. Hemiballism was abolished or considerably improved in 13
      (93%) of 14 patients in the immediate postoperative phase. Residual dyskinesia
      was evaluated using the hemiballism/hemichorea outcome rating scale. Long-term
      follow-up review was available for 13 of the 14 patients (mean follow-up period
      11 years). Persistent improvement in the hemiballism was found in 12 of these 13
      patients: seven patients (54%) were free of any hyperkinesia and five patients
      (39%) had minor residual and predominantly hemichoreic hyperkinesia. One of the
      13 patients presented with a probable psychogenic movement disorder at long-term
      follow-up examination. Persistent morbidity, most likely related to the operative
      intervention, was detected in three of the 13 patients; this included mild
      hemiparesis and dystonia. Functional disability was assessed using the
      Huntington's Disease Activities of Daily Living scale. The patients' preoperative
      mean value of 83% of maximum disability was reduced to a mean of 30% observed at
      long-term follow-up review (p < 0.001). The residual disability exhibited in most
      older patients was associated with cardiovascular disease. The authors compare
      their findings with the results of 44 cases reported previously. The authors
      contend that functional stereotactic surgery should be considered in patients
      with persistent, medically refractory hemiballism.

PMID- 8755758
TI  - Frameless stereotaxy with real-time tracking of patient head movement and
      retrospective patient-image registration.
AB  - The accuracy of a novel frameless stereotactic system was determined during 10
      surgeries performed to resect brain tumors. An array of three charge-coupled
      device cameras tracked the locations of infrared light-emitting diodes on a hand
      held stylus and on a reference frame attached to the patient's skull with a
      single bone screw. Patient-image registration was achieved retrospectively by
      digitizing randomly chosen scalp points with the system and fitting them to a
      scalp surface model derived from magnetic resonance (MR) images. The reference
      frame enabled continual correction for patient head movements so that
      registration was maintained even when the patient's head was not immobilized in a
      surgical clamp. The location of the stylus was displayed in real-time on cross
      sectional and three-dimensional MR images of the head; this information was used
      to predict the locations of small intracranial lesions. The average distance (and
      standard deviation) between the actual position of the mass and its
      stereotactically predicted location was 4.8 +/- 3.5 mm. The authors conclude that
      frameless stereotaxy can be used for accurate localization of intracranial masses
      without resorting to using fiducial markers during presurgical imaging and
      without immobilizing the patient's head during surgery.

PMID- 8755759
TI  - Neuroendoscopic approach to arachnoid cysts.
AB  - A prospective study of seven consecutive patients with congenital arachnoid cysts
      treated endoscopically is reported. The ages of the patients at the time of
      diagnosis ranged from 6 to 47 years with three patients under 15 years. Two cysts
      were located in the posterior cranial fossa, four in the middle cranial fossa,
      and one in the suprasellar-prepontine area. The patients' symptoms included
      headache, seizures, vomiting, nausea, dizziness, balance problems, and precocious
      puberty. The authors performed cystocisternostomies and ventriculocystostomies
      via burr holes with the aid of a universal neuroendoscopic system. Minor bleeding
      was easily controlled by rinsing. In one case, the endoscopic procedure had to be
      abandoned because of significant bleeding, which obscured a clear operative view,
      and an open microsurgical cyst fenestration was performed. The follow-up review
      periods in this group of patients ranged from 15 to 30 months. There was no
      mortality or morbidity. Symptoms were relieved in five patients and improved in
      one. Precocious puberty in one case continued. In six cases, follow-up magnetic
      resonance images or computerized tomography scans revealed a decrease in the size
      of the cysts. Although the follow-up period is too short to make statements on
      long-term outcome, the authors recommend the minimally invasive endoscopic
      approach for treatment of arachnoid cysts as the first therapy of choice. Should
      the endoscopic procedure fail, established treatment options such as
      microsurgical fenestration or cystoperitoneal shunting can subsequently be
      performed without causing additional risk to the patient.

PMID- 8755760
TI  - Application of magnetic resonance neurography in the evaluation of patients with
      peripheral nerve pathology.
AB  - Currently, diagnosis and management of disorders involving nerves are generally
      undertaken without images of the nerves themselves. The authors evaluated whether
      direct nerve images obtained using the new technique of magnetic resonance (MR)
      neurography could be used to make clinically important diagnostic distinctions
      that cannot be readily accomplished using existing methods. The authors obtained
      T2-weighted fast spin-echo fat-suppressed (chemical shift selection or inversion
      recovery) and T1-weighted images with planes parallel or transverse to the long
      axis of nerves using standard or phased-array coils in healthy volunteers and
      referred patients in 242 sessions. Longitudinal and cross-sectional fascicular
      images readily distinguished perineural from intraneural masses, thus predicting
      both resectability and requirement for intraoperative electrophysiological
      monitoring. Fascicle pattern and longitudinal anatomy firmly identified nerves
      and thus improved the safety of image-guided procedures. In severe trauma, MR
      neurography identified nerve discontinuity at the fascicular level
      preoperatively, thus verifying the need for surgical repair. Direct images
      readily demonstrated increased diameter in injured nerves and showed the linear
      extent and time course of image hyperintensity associated with nerve injury.
      These findings confirm and precisely localize focal nerve compressions, thus
      avoiding some exploratory surgery and allowing for smaller targeted exposures
      when surgery is indicated. Direct nerve imaging can demonstrate nerve continuity,
      distinguish intraneural from perineural masses, and localize nerve compressions
      prior to surgical exploration. Magnetic resonance neurography can add clinically
      useful diagnostic information in many situations in which physical examinations,
      electrodiagnostic tests, and existing image techniques are inconclusive.

PMID- 8755761
TI  - Orientation landmarks of endoscopic transaxillary T-2 sympathectomy for palmar
      hyperhidrosis.
AB  - The identification of the T-2 ganglion through a narrow operative viewfield is
      the greatest challenge in performing endoscopic transaxillary T-2 sympathectomy,
      especially for a surgeon who is unfamiliar with the technique. The authors
      describe a simple anatomical method for identifying the T-2 ganglion during the
      operation, based on a study of 17 adult cadavers. First, a similar clinical
      procedure was performed along the anterior or middle axillary line via the second
      to fourth intercostal spaces to measure the aiming angles and intrathoracic depth
      needed. Second, the regional anatomical structures and their relationship to
      bilateral T-2 ganglia were delineated. It was discovered that the superior
      intercostal artery, a branch of the subclavian artery, was an accessible
      landmark. This small vessel existed in 87.5% of the cadavers studied. It
      consistently runs lateral to the parallel sympathetic chain at an average
      distance of 10 mm. Most important is that it can be easily distinguished where it
      runs across the inner part of the second rib. The authors emphasize that the
      superior intercostal artery should be a very beneficial landmark for surgical
      orientation.

PMID- 8755762
TI  - Biomechanical characteristics of C1-2 cable fixations.
AB  - The biomechanical characteristics of four different methods of C1-2 cable
      fixation were studied to assess the effectiveness of each technique in restoring
      atlantoaxial stability. Biomechanical testing was performed on the upper cervical
      spines of four human cadaveric specimens. Physiological range loading was applied
      to the atlantoaxial specimens and three-dimensional motion was analyzed with
      stereophotogrammetry. The load-deformation relationships and kinematics were
      measured, including the stiffness, the angular ranges of motion, the linear
      ranges of motion, and the axes of rotation. Specimens were nondestructively
      tested in the intact state, after surgical destabilization, and after each of
      four different methods of cable fixation. Cable fixation techniques included the
      interspinous technique, the Brooks technique, and two variants of the Gallie
      technique. All specimens were tested immediately after fixation and again after
      the specimen was fatigued with 6000 cycles of physiological range torsional
      loading. All four cable fixation methods were moderately flexible immediately;
      the different cable fixations allowed between 5 degrees and 40 degrees of
      rotational motion and between 0.6 and 7 mm of translational motion to occur at C1
      2. The Brooks and interspinous methods controlled C1-2 motion significantly
      better than both of the Gallie techniques. The motion allowed by one of the
      Gallie techniques did not differ significantly from the motion of the unfixed
      destabilized specimens. All cable fixation techniques loosened after cyclic
      loading and demonstrated significant increases in C1-2 rotational and
      translational motions. The bone grafts shifted during cyclic loading, which
      reduced the effectiveness of the fixation. The locations of the axes of rotation,
      which were unconstrained and mobile in the destabilized specimens, became altered
      with cable fixation. The C1-2 cables constrained motion by shifting the axes of
      rotation so that C-1 rotated around the fixed cable and graft site. After the
      specimen was fatigued, the axes of rotation became more widely dispersed but were
      usually still localized near the cable and graft site. Adequate healing requires
      satisfactory control of C1-2 motion. Therefore, some adjunctive fixation is
      advocated to supplement the control of motion after C1-2 cable fixation (that is,
      a cervical collar, a halo brace, or rigid internal fixation with transarticular
      screws).

PMID- 8755763
TI  - Neural connection between the ventral portion of the lumbar intervertebral disc
      and the groin skin.
AB  - This study was designed to investigate neural mechanisms of referred pain in
      lumbar intervertebral disc lesions. Patients with a degenerative disc in lower
      lumbar segments occasionally complain of groin pain, which cannot be explained
      anatomically as having a radicular origin. In rats pretreated with intravenous
      application of Evans blue dye, the dye extravasation appeared in the groin skin
      after application of capsaicin to the ventral portion of the L5-6 intervertebral
      disc. This response occurred even in rats with a sectioned L-5 spinal nerve and
      sympathetic trunks, but did not occur in rats with a sectioned genitofemoral
      nerve. Capsaicin topically applied to the sciatic nerve did not cause dye
      extravasation in the hindpaw. Therefore, groin dye extravasation was not due to a
      direct effect of capsaicin but, rather, presumably was caused by an "antidromic
      axon reflex" of dichotomizing C fibers or to a segmental sympathetic reflex
      causing vascular permeability. The present results indicate that the ventral
      portion of the lumbar discs is neurally connected to the groin skin via the upper
      (L-2) lumbar spinal nerves in rats. Groin pain coincident with low-back pain may
      be explained as referred pain, indicating that a lesion is present in the ventral
      portion of the lumbar intervertebral disc space.

PMID- 8755764
TI  - Inhibition of cellular growth and induction of apoptosis in pituitary adenoma
      cell lines by the protein kinase C inhibitor hypericin: potential therapeutic
      application.
AB  - Protein kinase C (PKC) is an enzyme involved in the regulation of cellular
      growth, proliferation, and differentiation in a number of tissues including the
      anterior pituitary, in which it is also believed to play a role in hormone
      secretion. Protein kinase C activity and expression have been found to be greater
      in adenomatous pituitary cells than in normal human and rat pituitary cells and
      higher in invasive pituitary tumor cells than in noninvasive ones. Inhibition of
      PKC activity has been shown in a variety of tumor cells to inhibit growth in a
      dose-related fashion. The purpose of the current study was to determine whether
      hypericin, a potent inhibitor of PKC activity that may be administered
      clinically, alters the growth and proliferation in established pituitary adenoma
      lines and to determine if inhibition of PKC activity induces apoptosis, as
      reported in some other tumor cell types. Two established pituitary adenoma cell
      lines, AtT-20 and GH4C1, were treated with hypericin in tissue culture for
      defined periods following passage. Inhibition of growth was found to be dose
      dependent in all three cell lines in low micromolar concentrations of hypericin,
      as determined by viable cell counts, methylthiotetrazole assay, and [3H]thymidine
      uptake studies. Concentrations of hypericin as low as 100 nM also induced
      apoptosis in these established lines, whereas treatment of normal human
      fibroblasts with a concentration of 10 microM failed to induce apoptosis. The
      potential use of hypericin in the therapy of pituitary adenomas warrants
      additional in vitro investigations with the aim of later moving toward
      therapeutic trials in selected patients in whom surgical or medical therapy has
      failed.

PMID- 8755765
TI  - Thrombin-soaked gelatin sponge and brain edema in rats.
AB  - Previous work from this laboratory has shown that injection of thrombin into rat
      basal ganglia causes brain edema. This study investigates the effect on rat brain
      of thrombin-soaked gelatin sponge (used for intraoperative hemostasis in clinical
      situations) at a concentration similar to that used in humans. Three models were
      developed to evaluate this effect. In the first model, a gelatin sponge soaked
      with vehicle or thrombin (100 U/cm3) was placed on the intact pia of the right
      frontal lobe in rats without cortical lesions. In the second model, frontal
      cortex was excised (3 mm3) and the exposed brain was cauterized with
      electrocoagulation. Gelatin sponge was soaked with vehicle or thrombin (1000,
      100, 10, or 1 U/cm3) and placed in the lesion site. In the third model, hirudin,
      a specific thrombin antagonist, was added to the thrombin-soaked gelatin sponge
      and placed in a similar cortical lesion to determine if the observed effects were
      specific to thrombin. The dose-response range for thrombin was determined
      qualitatively by magnetic resonance (MR) imaging and quantitatively by brain
      edema formation 24 hours after exposure. We found no edema in the cortically
      intact rats. The rats given cortical lesions developed significant edema when
      subjected to 1000, 100, and 10 U/cm3 thrombin as seen on MR imaging and at 100
      and 10 U/cm3 thrombin as revealed by wet/dry weight and ion studies of brain
      tissue. Topical hirudin prevented thrombin-induced edema. It is concluded that
      thrombin-soaked gelatin sponges cause or enhance significant brain edema in rats
      at concentrations typically used for human neurosurgery.

PMID- 8755767
TI  - Intraosseous glomus tumor of the spine. Case report and review of the literature.
AB  - The authors report a case of glomus tumor originating within the lumbar spine.
      Glomus tumors of intraosseous origin are rare, with the only case reported in the
      spine arising in the sacrum. The patient presented with the solitary complaint of
      radiating back pain that resolved postoperatively. The histopathological and
      radiographic findings are reviewed. To the authors' knowledge, this represents
      the first case report of a glomus tumor of the spine originating above the
      sacrum.

PMID- 8755766
TI  - Arteriovenous fistula as a complication of C1-2 transarticular screw fixation.
      Case report and review of the literature.
AB  - A case is reported of a vertebral artery-to-epidural venous plexus fistula as a
      complication of posterior atlantoaxial facet screw fixation. The use of
      transarticular screws to stabilize the C1-2 joint has become an increasingly
      popular fixation technique, most notably for atlantoaxial instability due to
      trauma or rheumatoid disease. Despite the fact that this approach is technically
      challenging, there have been few reports of complications associated with C1-2
      transarticular fixation. Although damage to the vertebral artery is a documented
      hazard of transarticular fixation at this level, a symptomatic arteriovenous
      fistula resulting from the procedure has not been described previously. The
      etiology, presentation, and treatment of this unusual complication are discussed.

PMID- 8755768
TI  - Symptomatic epidural lipomatosis secondary to obesity. Case report.
AB  - The authors present a case of thoracic spinal cord compression secondary to
      epidural lipomatosis in an obese patient. This patient represents the 10th case
      of epidural lipomatosis secondary to simple obesity reported in the literature.
      The diagnosis is based on three criteria: 1) medical history and physical
      examination consistent with segmental spinal cord compression; 2) epidural fat
      thickness greater than 7 mm in the region of compression, based on magnetic
      resonance imaging (preferred) or computerized tomographic imaging; and 3) a
      height-to-weight ratio greater than 27.5 kg/m2. This specific correlation between
      epidural fat thickness measurement and calculation of height-to-weight ratio has
      not previously been reported. Surgical decompression through a posterior
      laminectomy and excision of excess epidural fat resulted in immediate reversal of
      the patient's symptoms. Knowledge of the association of epidural lipomatosis with
      obesity in the absence of glucocorticoid imbalance is important in discerning
      what may be an underrecognized syndrome.

PMID- 8755769
TI  - Traumatic interdural arachnoid cyst in the upper cervical spine. Case report.
AB  - The case of an interdural arachnoid cyst of traumatic origin at the C3-5 level in
      an 18-year-old man was admitted to our hospital with a 1-year history of
      progressive weakness in left limbs and numbness below the clavicles is reported.
      He had had a C-2 fracture at the age of 9 years without definite neurological
      deficits. Magnetic resonance imaging revealed a cystic lesion in the C3-5 level.
      Laminectomy was performed, and an interdural cyst was found. Histological
      examination revealed fibrous thickening of the arachnoid membrane. A cyst located
      in the interdural space of upper cervical spine is extremely rare.

PMID- 8755770
TI  - Spinal extradural meningeal cyst. Case report.
AB  - The case of a 30-year-old man with a spinal extradural meningeal cyst in the
      thoracolumbar region is reported. Operative findings revealed a dural defect that
      allowed communication between the extradural cyst cavity and the subarachnoid
      space. Application of the Valsalva maneuver made the cerebrospinal fluid flow
      into the cyst cavity; however, reverse flow did not occur. These findings
      indicate that a valvelike mechanism developed in the enlarging cyst. Surgical
      resection of the cyst wall and closure of the dural defect provided a favorable
      result.

PMID- 8755771
TI  - A new instrument for improved accuracy of stereotactic depth electrode placement.
      Technical note.
AB  - A disadvantage of stereotactic placement of flexible depth electrodes is the risk
      of inaccurate positioning as a result of electrode movement when the introducer
      is withdrawn. A simple device that virtually eliminates this error is described.

PMID- 8755772
TI  - Extradural intrasphenoidal cavernous sinus schwannoma. Case illustration.

PMID- 8755773
TI  - Pituitary ectopic adenoma.

PMID- 8755774
TI  - Intraosseous meningioma.

PMID- 8755775
TI  - Near-infrared spectroscopy.

PMID- 8755776
TI  - Negative-pressure hydrocephalus.

PMID- 8755777
TI  - Cerebral perfusion pressure.

PMID- 8755778
TI  - Hetastarch Coagulopathy.

PMID- 8755779
TI  - Be the healer you profess to be.

PMID- 8755780
TI  - Senate bill would control sale of tobacco to minors.

PMID- 8755781
TI  - Die hard: end-of-life care in America.

PMID- 8755782
TI  - A prescription for healing the system.

PMID- 8755783
TI  - HCFA issues new Medicare rules for teaching physicians.

PMID- 8755784
TI  - PA health department offers information on DES.

PMID- 8755785
TI  - New treatments for new TB strains.
AB  - Since the discovery of penicillin in the 1930s and antituberculous agents a
      decade later, antimicrobial chemotherapy has advanced tremendously. New
      generations of older antibiotics and combinations of drugs have resulted in
      greater efficacy in the treatment of life-threatening infections. Yet multi-drug
      resistant tuberculosis remains a threat today, particularly in Pennsylvania.

PMID- 8755786
TI  - New therapeutic agents marketed in 1995.

PMID- 8755787
TI  - Frederic Ives Medal paper. History and current status of a physiologically based
      system of photometry and colorimetry.
AB  - The CIE chromaticity diagram, which has been in common use for more than 60
      years, disguises essential relations among cone excitations that become
      transparent in a system developed with D. I. A. MacLeod and initially proposed by
      the author to the CIE in 1979. This proposal led to the formation of a CIE
      committee to consider an ideal version of the system, to be employed either as a
      supplement to, or an alternative for, the 1931 "standard observer". After 15
      years, the task remains unfinished. The history of debate within the original
      committee and that of its successor (which is still active today) is briefly
      reviewed. Among cone fundamentals that might be chosen, a set derived and
      published by Stockman, MacLeod, and Johnson [J. Opt. Soc. Am. A 10, 2491 (1993)]
      is favored here, and some of the advantages for displaying visual data in a
      system based on these fundamentals are illustrated.

PMID- 8755788
TI  - Limitations of surface-color and apparent-color constancy.
AB  - Color-constancy mechanisms have been studied and discussed in a number of
      investigations. However, there has been little attempt to reveal how color
      constancy deteriorates as the conditions for it become less than optimal. We
      carried out a series of asymmetric color-matching experiments, using two
      criteria: surface-color match and apparent-color match. With brief adaptation the
      degree of color constancy increased as chromatic cues were added in the surround.
      In the condition of black surround, the test stimuli appeared self-luminous, and
      chromaticities of the chosen matching stimuli were the same as the physical
      chromaticities of the test stimulus, indicating a total deficiency of color
      constancy. With 15 min of preadaptation to the illuminant, the surface-color
      matches showed almost perfect color constancy under illuminant change. In both
      adaptation conditions, the chromatic-shift of matches from what would be expected
      for perfect color constancy increased gradually between 1,700- and 30,000-K
      illuminant, as chromaticity of the illuminant departed from 6,500-K illuminant.
      Under 1,000-K illuminant the surface-color appearance became totally achromatic,
      and color constancy was completely lost. Our results show that, even with brief
      adaptation to the illuminant, the contribution of the surrounding stimulus is
      large enough to achieve a fair degree of color constancy, but complete adaptation
      to the illuminant helps to achieve almost perfect color constancy.

PMID- 8755789
TI  - Continuum of care controversy.

PMID- 8755790
TI  - DSM-IV and sexuality.

PMID- 8755791
TI  - More on SSRI-induced mania.

PMID- 8755792
TI  - Guanfacine for PTSD nightmares.

PMID- 8755793
TI  - Behavioral manifestations of genetic disorder.

PMID- 8755794
TI  - Attention deficit disorder: a review of the past 10 years.
AB  - OBJECTIVE: To summarize knowledge about attention deficit disorder in the areas
      of epidemiology, etiology, clinical predictors, assessments, natural history and
      outcome, and management. METHOD: A literature review of articles, books, and
      chapters primarily published in the past 10 years was completed. Articles
      presenting new information, most relevant to clinical practice, were reviewed.
      RESULTS: Key findings in the areas listed above are presented. CONCLUSIONS: Major
      advances have been made in all areas. The clinical picture has been refined and
      developmental manifestations have been delineated. Patterns of comorbidity have
      been detailed. Various etiological factors, particularly in the biological area,
      have been investigated. Multimodal management has been promulgated as the
      treatment of choice.

PMID- 8755795
TI  - Relationship between ADHD and anxiety in boys: results from a family study.
AB  - OBJECTIVE: Recent studies have found an increased risk for both anxiety disorder
      and attention-deficit hyperactivity disorder (ADHD) in the adult relatives of
      children with ADHD in comparison with adult relatives of normal controls. Such
      findings may account for the high rates of comorbid anxiety found in children
      with ADHD, and they suggest a relationship between the two disorders. However,
      additional studies are needed to address this relationship that include both
      anxiety disorder and normal control groups. METHOD: The first- (n = 239) and
      second-degree relatives (n = 1,266) of clinically referred boys with ADHD (n =
      49), clinically referred boys with anxiety disorder (n = 46), and controls who
      have never been psychiatrically ill (NPI controls) (n = 37) were assessed with
      structured interview and diagnosed according to DSM-III-R criteria. Lifetime
      rates of ADHD and anxiety disorder were then compared for relatives in the three
      proband groups. RESULTS: Female relatives of ADHD probands had significantly
      higher rates of anxiety disorder than female relatives of NPI controls. However,
      relatives of anxious probands and NPI controls did not differ for ADHD.
      Furthermore, no evidence of cosegregation of anxiety disorder with ADHD was found
      in the relatives of probands in the two patient groups. CONCLUSIONS: ADHD and
      anxiety may share common risk factors but appear to be independently transmitted
      in families. The high rate of anxiety in female relatives of ADHD probands was
      comparable with that found in relatives of anxious probands and warrants further
      investigation.

PMID- 8755796
TI  - Attention-deficit hyperactivity disorder and juvenile mania: an overlooked
      comorbidity?
AB  - OBJECTIVE: To evaluate the psychiatric, cognitive, and functional correlates of
      attention-deficit hyperactivity disorder (ADHD) children with and without
      comorbid bipolar disorder (BPD). METHOD: DSM-III-R structured diagnostic
      interviews and blind raters were used to examine psychiatric diagnoses at
      baseline and 4-year follow-up in ADHD and control children. In addition, subjects
      were evaluated for cognitive, academic, social, school, and family functioning.
      RESULTS: BPD was diagnosed in 11% of ADHD children at baseline and in an
      additional 12% at 4-year follow-up. These rates were significantly higher than
      those of controls at each assessment. ADHD children with comorbid BPD at either
      baseline or follow-up assessment had significantly higher rates of additional
      psychopathology, psychiatric hospitalization, and severely impaired psychosocial
      functioning than other ADHD children. The clinical picture of bipolarity was
      mostly irritable and mixed. ADHD children with comorbid BPD also had a very
      severe symptomatic picture of ADHD as well as prototypical correlates of the
      disorder. Comorbidity between ADHD and BPD was not due to symptom overlap. ADHD
      children who developed BPD at the 4-year follow-up had higher initial rates of
      comorbidity, more symptoms of ADHD, worse scores on the CBCL, and a greater
      family history of mood disorder compared with non-BPD, ADHD children.
      CONCLUSIONS: The results extend previous results documenting that children with
      ADHD are at increased risk of developing BPD with its associated severe
      morbidity, dysfunction, and incapacitation.

PMID- 8755797
TI  - Quantitative EEG differences in a nonclinical sample of children with ADHD and
      undifferentiated ADD.
AB  - OBJECTIVE: To use quantitative electroencephalographic (EEG) techniques to
      identify electrophysiological differences between children with distinct
      disorders of attention and/or hyperactivity. METHOD: Forty children from a
      prescreened community sample were evaluated by means of both spectral EEG and
      evoked response potential (ERP) techniques. The children were 7 to 13 years of
      age and were selected on the basis of membership in one of the following DSM-III
      R categories: attention-deficit hyperactivity disorder (ADHD) (n = 16),
      undifferentiated attention deficit disorder (UADD) (n = 12), or no disruptive
      disorder diagnosis (n = 12). RESULTS: Spectral EEG revealed that UADD subjects
      had less delta band relative percent power (RPP) (p < .01), more beta band RPP (p
      < .01), and ERP findings of a decreased rare tone P300 amplitude (p < .02)
      compared with the control group. ADHD subjects had spectral EEG findings of
      increased beta band RPP (p < .05) and ERP findings of an increased common tone
      N100 latency (p < .02) and a decreased rare tone P300 amplitude (p < .02).
      Interhemispheric asymmetries appeared to distinguish the groups: the UADD group
      had spectral EEG asymmetries; the ADHD group had only ERP asymmetries; and the
      control group had no asymmetries. CONCLUSION: Quantitative EEG techniques may
      prove useful in differentiating specific subtypes of ADHD.

PMID- 8755798
TI  - An open trial of pemoline in drug-dependent delinquents with attention-deficit
      hyperactivity disorder.
AB  - OBJECTIVE: Adolescents with conduct disorder and substance use disorders have
      high rates of comorbid attention-deficit hyperactivity disorder (ADHD); ADHD may
      contribute to the severity and persistence of substance use disorders and
      antisocial behaviors. Treatment of ADHD may help patients utilize substance and
      other behaviorally focused treatment. Yet little is known about the response of
      ADHD symptoms to psychopharmacological intervention in substance-dependent
      delinquents. METHOD: Pilot data are presented for 13 male adolescents with
      conduct disorder, substance use disorders, and ADHD, in a residential substance
      use treatment program. Patients were treated with pemoline. Scores from the
      Conners Hyperactivity Index and continuous performance tasks were obtained at
      baseline and after about 1 month of treatment with pemoline. Physical activity
      measurements were also assessed at baseline and 1 month. Postmedication
      assessments were obtained after at least 1 week at maximal dosage (1.2 to 3.3
      mg/kg). RESULTS: Mean Conners Hyperactivity Index scores declined 13.9% (p < or =
      .002) and mean motility declined 7% (p < or = .04) with pemoline treatment.
      Continuous performance task scores did not change. CONCLUSIONS: Preliminary data
      indicate that pemoline may be a useful treatment for ADHD in substance-dependent
      delinquents; the authors propose a controlled trial of pemoline in such youths.

PMID- 8755799
TI  - A comparison of measures of adjustment, symptoms, and impairment among children
      with chronic medical conditions.
AB  - OBJECTIVE: To examine the concurrent and criterion validity of three instruments
      used to measure emotional and behavioral problems among children with chronic
      illness. METHOD: The Personal Adjustment and Role Skills Scale (PARS III), Child
      Behavior Checklist (CBCL), and Columbia Impairment Scale (CIS) were compared with
      each other and with structured interview-derived psychiatric diagnoses in 116
      chronically ill children, aged 9 to 18 years. Three cutoff scores were used for
      each measure. RESULTS: The measures had good concurrent validity despite only
      moderate agreement with each other. Their criterion validity was only fair:
      levels of sensitivity were fair at low cutoffs and poor at standard and high
      cutoffs; specificity and positive predictive values rose from moderate at low
      cutoffs to high at standard and high cutoffs. The agreement between the scales
      and a mental disorder diagnosis was only moderate at any of the cutoff points.
      CONCLUSIONS: Each of these measures has significant limitations. Both the CBCL
      and the PARS III appear to measure similar constructs but are likely to
      underidentify medically ill children with comorbid psychiatric problems.
      Consideration of global functioning across domains, with a measure such as the
      CIS, might provide an alternative approach to behavioral and symptom checklists
      in the assessment and management of children with chronic conditions.

PMID- 8755800
TI  - Symptom perception in pediatric asthma: relationship to functional morbidity and
      psychological factors.
AB  - OBJECTIVE: Perception of changes in respiratory symptoms is a critical element in
      the self-management of pediatric asthma. The purpose of this study was to
      quantify perceptual accuracy in childhood asthma, to investigate links between
      symptom perception and functional morbidity, and to examine relationships between
      psychological variables and perceptual accuracy. METHOD: Eighty-six children,
      aged 8 to 15 years, attending an asthma camp made subjective estimates of asthma
      severity immediately prior to spirometry an average of 31 times at camp. The
      correlation coefficient between these measures (the child's accuracy index) was
      analyzed in relation to morbidity data and to scores on instruments that assessed
      trait anxiety, repressive coping style, intelligence, behavior problems, and
      parental symptom-reporting patterns. RESULTS: A wide range of perceptual ability
      was found, as children's subjective-objective r ranged from-.39 to .88. Greater
      perceptual accuracy was significantly related to fewer days missed from school
      and fewer emergency medical visits. Of the psychological variables assessed, only
      intelligence was significantly related to accuracy. CONCLUSIONS: Symptom
      perceptual ability is an important psychosomatic factor affecting the course of
      asthma for some children. Further study is indicated to understand psychological
      variables in addition to intelligence that may determine a child's perceptual
      accuracy.

PMID- 8755802
TI  - Case study: hypersomnolence and precocious puberty in a child with pica and
      chronic lead intoxication.
AB  - The limited literature on hypersomnolence suggests that it is a poorly defined
      symptom associated with a spectrum of disorders from monosymptomatic
      hypersomnolence to the Kleine-Levin syndrome. These disorders often herald an
      organic central nervous system syndrome. Recent evidence suggests a frequent
      association between these disorders and hypothalamic dysfunction, which itself
      may be caused by a variety of factors. This case study of a patient with
      persistent hypersomnolence, hypothalamic dysfunction (in the form of precocious
      puberty), pica, and chronic lead intoxication strengthens the association between
      hypersomnolence and hypothalamic dysfunction and suggests a heretofore unreported
      cause of hypothalamic dysfunction in humans.

PMID- 8755801
TI  - Psychiatric family history in adolescents with severe asthma.
AB  - OBJECTIVE: To examine the hypothesis that an association exists between severe
      asthma and familial affective and anxiety disorders. METHOD: A parent, usually
      the mother, of 62 adolescents admitted to a tertiary care asthma center was
      administered the Family History-Research Diagnostic Criteria Interview. Lifetime
      prevalence rates of psychiatric disorders in first-degree relatives were compared
      with previously reported rates. RESULTS: In relatives of asthmatic adolescents,
      rates for depression, mania (females only), substance abuse (males only), and
      antisocial personality disorder were significantly higher than the rates in the
      non-ill comparison sample. Rates for substance abuse (males only) and antisocial
      personality disorder were higher than the rates for relatives of the depressed
      comparison sample. Rates for anxiety disorders were not higher than rates in
      epidemiological samples. Rates of attention-deficit hyperactivity disorder
      (females only) and posttraumatic stress disorder in relatives were higher than in
      community samples. CONCLUSIONS: These results support the presence of a link
      between severe asthma and familial affective disorders, posttraumatic stress
      disorder, antisocial personality disorder, and substance abuse. Whether these
      disorders are genetically associated with asthma or represent an association with
      severe asthma because of environmental effects on the growing child is discussed.

PMID- 8755803
TI  - Outcomes of mental health care for children and adolescents: I. A comprehensive
      conceptual model.
AB  - OBJECTIVE: Accountability for mental health care has become a standard of
      clinical practice. With the expansion of managed care as a corporate response to
      health reform, attention to outcomes will intensity. Assessment of clinical
      treatment has typically focused on symptom reduction at an individual level,
      whereas assessment of service effectiveness has more often targeted service-level
      change. METHOD: A dynamic and interactional model of outcomes is presented that
      broadens the range of intended consequences of care. The model comprises five
      domains: symptoms, functioning, consumer perspectives, environmental contexts,
      and systems. RESULTS: The model reflects the changeable interaction between
      children's evolving capacities and their primary environments (home, school, and
      community). CONCLUSIONS: As health care practices shift, attention to improved
      care is likely to depend increasingly on scientifically credible evidence of its
      impact. Greater integration between research and standard practice will be
      needed. Such a partnership can be strengthened by a more comprehensive view of
      the impact of care.

PMID- 8755804
TI  - Outcomes of mental health care for children and adolescents: II. Literature
      review and application of a comprehensive model.
AB  - OBJECTIVE: Using a comprehensive model of outcomes, the authors review the
      scientific literature to determine the extent of knowledge concerning the
      outcomes of mental health care for children and adolescents. METHOD: Previous
      research is examined to determine the degree to which it addresses five salient
      outcome domains: symptoms/diagnoses, functioning, consumer perspectives,
      environments, and systems (the SFCES model). RESULTS: Despite numerous studies,
      only 38 met minimal scientific criteria. They generally fall into two categories,
      according either to their focus on the efficacy of treatment(s) for specific
      disorders or the effectiveness of a particular service or service system. Only
      two studies include outcome assessments across all five domains. CONCLUSIONS: As
      health care practices shift, improvements in mental health care will require
      credible evidence detailing the impact of clinical treatments and services on all
      salient outcome domains. Embedding efficacious treatments into effective service
      programs will likely improve care, but treatments will require modification to
      make them flexible, inclusive, and appropriate to multicultural populations.
      Furthermore, service delivery systems must be modified to meet the specific
      clinical needs of children with mental disorders and to embrace new efficacious
      treatments as they become available.

PMID- 8755805
TI  - Integrating assessment data from multiple informants.
AB  - OBJECTIVE: To examine the consequences for measurement of child psychiatric
      disorder (conduct and oppositional disorders) of not integrating the data on the
      same individual from different informants compared with integrating the
      information from parents and teachers, using three different strategies. METHOD:
      Data for the study came from problem checklist assessments done by parents and
      teachers of children aged 6 to 16 years (N = 1,134) selected with known
      probability from a general population sample and from structured interviews
      obtained in a stratified random subsample (n = 251). RESULTS: As expected, parent
      teacher agreement was low. The pattern of associated features of disorder was
      found to vary markedly in parent-identified compared with teacher-identified
      disorder. Furthermore, combining informants had the disadvantage of masking the
      distinctive patterns of associated features noted in informant-specific
      disorders. Finally, by treating disorder as informant-specific, the internal
      properties of the measure are not generally inferior to those obtained by
      combining informants in various ways. CONCLUSION: Child psychiatric disorders
      should be conceptualized as informant-specific phenomena.

PMID- 8755807
TI  - Foster children in acute crisis: assessing critical aspects of attachment.

PMID- 8755806
TI  - Help-seeking preceding mental health clinic intake among African-American,
      Latino, and Caucasian youths.
AB  - OBJECTIVE: Pathways into child mental health clinics were studied to test this
      hypothesis: Prior to contacting clinics for their child's problems, African
      American and Latino families are less likely than Caucasian families to seek help
      from agencies and professionals (and more likely to contact family and community
      sources). METHOD: Regression analyses, applied to a sample of 192 clinic-admitted
      families, assessed the impact of ethnicity and income, child gender and age, and
      parent perceptions of child problem severity and likely treatment benefit, on
      preclinic help-seeking. RESULTS: As predicted, African-American and Latino
      families, compared with Caucasian families, sought help from professionals and
      agencies much less often, as a first step and as a percentage of all their
      preclinic help-seeking. With income, age, gender, and parent perceptions in the
      model, both African-American and Latino families were 0.37 as likely as Caucasian
      families to seek initial help from a professional or agency. CONCLUSION: Although
      many minority youths are admitted to mental health clinics, seeking help from
      professionals may not have been their parents' preference. The apparent
      reluctance of minority parents carries implications for clinical intervention and
      alliance formation with minority group families and for the design and evaluation
      of ethnic community outreach programs.

PMID- 8755808
TI  - Hepatitis C virus and organ transplantation.
AB  - Hepatitis C virus (HCV) is both the leading cause of cirrhosis and hepatic
      failure leading to liver transplantation and a cause of chronic hepatitis in
      approximately 10% of all transplant recipients. Beginning 5-10 years or more
      posttransplant, HCV causes progressive liver disease in a significant fraction of
      infected individuals and contributes to an increased incidence of opportunistic
      infection and hepatocellular carcinoma. The existence of multiple genotypes of
      HCV with differing biologic behaviors and the generation of antigenic diversity
      of the virus (quasispecies) during the course of infection, limit the capacity of
      the immune system to generate protective immunity. Antiviral therapy with
      interferon-alpha is effective in only a minority of transplant patients, and
      since allografts from HCV infected donors are quite efficient in transmitting the
      virus, great attention is paid to the appropriate use of organs from HCV-positive
      donors. At present, these organs should be particularly targeted for patients in
      emergent need of lifesaving heart, liver, or lung transplants. Issues requiring
      further investigation include the impact of viral superinfection on HCV-infected
      recipients of organs from HCV-infected donors and the use of such organs in
      seronegative patients who are older, diabetic, or highly sensitized, for whom
      quality of life issues may outweigh the long-term impact of HCV infection.

PMID- 8755809
TI  - Targeting gene expression to endothelial cells in transgenic mice using the human
      intercellular adhesion molecule 2 promoter.
AB  - Genetic engineering of donor animals in xenotransplantation research has been
      directed largely toward obtaining expression of various immunoregulatory
      molecules on vascular endothelium, the initial target of recipient antibody and
      complement. However, specific high-level expression of transgenes throughout the
      vascular tree in adult animals has proved difficult to achieve, perhaps because
      of the inherent heterogeneity of endothelium. Using the promoter of the gene for
      intercellular adhesion molecule 2 (ICAM-2), which is constitutively expressed on
      all vascular endothelium, we have developed a system for endothelial cell gene
      targeting in vivo. A 334-basepair fragment from the 5' flanking region of the
      human ICAM-2 gene was used to drive the expression of human CD59 in transgenic
      mice. Strong and uniform expression of CD59 was observed on the endothelial cells
      of all blood vessels in the heart, kidney, lung, liver, and pancreas in the three
      lines of mice examined. Little or no expression was seen in other cell types,
      with the exception of neutrophils and monocytes. These results suggest that this
      small promoter region contains most of the signals necessary to endow it with
      endothelial cell specificity, making it a potentially valuable tool in areas
      ranging from xenotransplantation to gene therapy.

PMID- 8755810
TI  - Oxygen free radical content and neutrophil infiltration are important
      determinants in mucosal injury after rat small bowel transplantation.
AB  - Mucosal injury is an immediate event following revascularization of small
      intestinal grafts in the context of transplantation (SBTx). The generation of
      oxygen free radicals (OFR) and tissue infiltration by activated neutrophils are
      consequences of ischemia and reperfusion and known causative factors of tissue
      injury; to delineate their role in the reperfusion injury occurring after cold
      preservation of the intestine and subsequent transplantation was the aim of this
      study. Prior to orthotopic SBTx in Sprague-Dawley rats, grafts were stored in
      cold (4 degrees C) Ringer's lactate solution for 1 (n=6), 2 (n=7), and 4 hr
      (n=7). Small bowel biopsy specimens were obtained before harvesting, at the end
      of the (cold) ischemic period and immediately before unclamping (i.e., before
      revascularization) and 30, 60, 120 min, and 24 hr after transplantation to
      evaluate tissue injury by histology, OFR production, (measured by luminol
      enhanced chemiluminescence [LCL]), and the degree of neutrophil infiltration by
      myeloperoxidase staining. Reperfusion of the graft significantly worsened the
      histologically graded mucosal injury compared with that seen before unclamping.
      However, 24 hr after engraftment, mucosal morphology was restored almost
      completely. OFR production increased significantly during the early phases of
      reperfusion (30, 60, and 120 min) and returned to control values after 24 hr.
      Reperfusion of the graft was associated with a marked increase in the number of
      mucosal neutrophils. The present study indicates that OFR production and
      neutrophilic infiltration commence and progressively increase with graft
      reperfusion. These changes parallel the mucosal injury. Ischemic intervals of 4
      hr were not associated with a statistically significant greater ischemic-injury
      patterns compared with 1- and 2-hr intervals. The profound changes associated
      with reperfusion probably overshadow the minor, yet likely, progressive injury
      patterns associated with longer ischemia times.

PMID- 8755811
TI  - The beneficial effect of dibutyryl cyclic adenosine monophosphate on warm
      ischemic injury of the rat liver induced by cardiac arrest.
AB  - Dibutyryl cAMP (DBcAMP) has a high membrane permeability, and maintenance of the
      intracellular cAMP concentration may improve the viability of organs. In this
      study, the effect of DBcAMP pretreatment on warm ischemic injury of rat livers
      was evaluated. Warm ischemic liver injury was induced in adult Wistar rats
      weighing 250-280 g by leaving them at room temperature (22-25 degrees C) after
      cardiac arrest. The hepatic cAMP concentration, %ATP, and trypan blue-positive
      nuclear ratio were determined after different durations of warm ischemia. In
      addition, transaminase and endothelin-1 (ET-1) release into the perfusate were
      examined during 60 min of isolated liver perfusion with Krebs-Henseleit solution.
      The optimal dose and time of DBcAMP pretreatment were determined to be 15 mg/kg
      and 60 min prior to warm ischemia, respectively. Data on the trypan blue-positive
      nuclear ratio and the release of transaminases and ET-1 revealed that warm
      ischemia first damaged the endothelial cells and then the hepatocytes. DBcAMP
      pretreatment appeared to protect the liver from warm ischemic injury by
      increasing the intracellular cAMP concentration and stabilizing the cell
      membranes of endothelial cells and hepatocytes.

PMID- 8755812
TI  - Characterization of hypothermic intestinal ischemia-reperfusion injury in dogs.
      Effects of glycine.
AB  - The effects of 48 hr of hypothermic (4 degrees C ischemia) and short-term
      reperfusion. (I-R) on intestinal function and metabolism were studied in dogs
      utilizing Collins flush alone or with the putative cytoprotectant amino acid,
      glycine. Intestinal blood flow after hypothermic ischemia in Collins-flushed
      segments briefly rose at reperfusion, rapidly declined after 5 min, and plateaued
      over the 60-minute reperfusion period. Paired intestinal segments flushed with 5
      mM glycine demonstrated parallel changes in blood flow over the reperfusion
      period, but the blood flow values were significantly higher (100-300%), relative
      to the Collins segments. Intestinal oxygen consumption (VO2) was about 50% of
      normal nonischemic intestinal segments at all times after reperfusion. The
      glycine-flushed intestinal segments significantly consumed about 100% more
      oxygen, relative to the paired control intestines. Intestinal fluid and protein
      flux into the lumen significantly increased after I-R in both glycine- and
      Collins-flushed segments. Mucosal tissue myeloperoxidase (MPO) activity, a
      biochemical marker of neutrophils, significantly increased after 48 hr of cold
      ischemia with Collins flush and 1 hr of reperfusion, relative to tissue obtained
      before ischemia. The reperfusion-induced increase in MPO activity was abolished
      in intestinal segments flushed with glycine. Mucosal synthesis of the
      chemoattractant leukotriene B4 (LTB4) significantly increased after I-R and
      glycine flush abolished these increases. Nitric oxide synthesis by mucosal tissue
      in Collins-flushed segments subjected to 48 hr of hypothermic ischemia and 1 hr
      of reperfusion was significantly higher, compared with nonischemic tissue or
      mucosal tissue subjected to cold ischemia without reperfusion. Glycine flush did
      not alter this pattern of NO synthesis. Light microscopic analysis in both
      Collins- and glycine-flushed segments revealed that intestinal hypothermic
      ischemia and reperfusion caused significant morphologic changes characterized by
      loss of villus epithelium, decreased villus height, and venous congestion. These
      data indicate that glycine significantly improve oxygenation after hypothermic
      ischemia and reperfusion and prevented the I-R-induced increase in tissue
      neutrophil infiltration and leukotriene synthesis.

PMID- 8755813
TI  - Protection of isolated lung from reperfusion injuries by rinsing with high
      colloidal osmotic solution with deferoaxmine.
AB  - We examined the efficacy of rinsing isolated lungs subjected to prolonged
      hypothermic storage with a high colloidal osmotic pressure solution prior to ex
      vivo blood reperfusion in order to preserve physiologic functions, suppress
      peroxidation of mitochondrial membranes, and inhibit infiltration of neutrophils.
      Isolated rabbit lungs were flushed with a Rinse-1 solution (289 mOsm/kg H2O) to
      remove remaining blood and immersed in physiologic saline at 8 degrees C for 24
      hr. The control group received blood reperfusion immediately after storage; the
      Rinse-1 group was rinsed with Rinse-1 solution before blood reperfusion and the
      Rinse-2 group with Rinse-2 solution (312 mOsm/kg H20) including deferoxamine.
      Reperfused blood was passed through an artificial membranous lung to reduce
      oxygen tension (PO2) to the venous level, and time-dependent changes in airway
      pressure (AWP), pulmonary artery pressure (PAP), and PO2, as a measure of gas
      exchange capability were examined. We estimated the lipid peroxide level in
      mitochondrial membranes as thiobarbituric acid-reactive substances (TBARS), i.e.,
      malonedialdehyde, and neutrophil infiltration into lung tissue by measuring
      myeloperoxidase activity after 60 min of blood reperfusion. The PO2 was
      significantly higher in both rinsed groups compared with the control, while
      neither AWP nor PAP was significantly different in the three treatment groups.
      Both mitochondrial TBARS and myeloperoxidase activity were significantly higher
      in the control group compared with either rinsed group. These results indicate
      that rinsing stored lungs with a solution of high colloidal osmotic pressure
      prior to blood reperfusion was effective in preserving physiologic function and
      inhibiting neutrophil infiltration. Addition of deferoxamine was markedly
      effective in reducing TBARS formation and lessening reperfusion injury of stored
      lungs.

PMID- 8755814
TI  - Noncompliance in children and adolescents after renal transplantation.
AB  - This study assesses the perceptions, knowledge, and attitudes of patients and
      parents attending the Pediatric Transplant Unit at the Johannesburg Hospital.
      Fifty-six children with renal transplants accompanied by their parents were
      assessed by means of a questionnaire. The children's ages were 2.53 to 20.85
      years. Eleven of twelve in the noncompliant group were male and nine were Black.
      The ages of the two groups of patients and distance traveled to the transplant
      center were similar. The noncompliant group of patients more often missed clinic
      visits (50% vs. 14%), P=0.0201; forgot to take their medications (50% vs. 23%);
      and took more medications (10.3 +/- 3.0 vs. 7.5 +/- 2.0) and remembered fewer of
      their names (4.0 +/- 3.5 vs. 6.5 +/- 2.5), P=0.0001 than the compliant group. The
      noncompliant patients knew less about their disease (50% vs. 8.3%) P=0.0141,
      allograft (53% vs. 33%), and immunosuppression (66% vs. 200%) P=0.0217, than the
      compliant patients. A total of 9% of the patients (5/56) were concerned about
      immunosuppressive side-effects, and indicated that this affected their
      compliance. Families wanted additional information, both pretransplant (52%) and
      posttransplant (45.5%). In addition, 85% wanted ongoing in-house education
      concerning transplantation and medications. Pediatric renal transplant patients
      and their families require ongoing education, support, medication evaluation, and
      compliance surveillance. Patients at high risk of noncompliance require directed
      additional intervention.

PMID- 8755815
TI  - Immunolocalization of FGF-1 and receptors in glomerular lesions associated with
      chronic human renal allograft rejection.
AB  - Glomerular lesions are considered one of the more detrimental pathologic changes
      associated with chronic rejection of renal allografts. To elucidate potential
      pathophysiologic mechanisms associated with transplant glomerulopathy, we
      examined the expression of acidic fibroblast growth factor (FGF-1) and its high
      affinity receptors (FGFR) in both relevant renal transplant controls (n=5) and
      tissue from patients (n=19) who underwent nephrectomy following graft loss
      secondary to chronic rejection. In situ immunohistochemical analyses demonstrated
      minimal staining and distribution of FGFR and FGF-1, which was localized to the
      mesangial matrix in glomeruli from normal human kidneys. In situ hybridization
      failed to detect the presence of FGF-1 mRNA in control tissue. In contrast, each
      stage of the developing glomerular lesion associated with chronic rejection
      demonstrated the exaggerated appearance of FGF-1 protein in visceral and parietal
      epithelial cells. Intense staining for FGF-1 protein did not correlate with the
      increased appearance of FGF-1 mRNA, which was restricted to circulating
      inflammatory cells. Glomeruli in kidneys with findings of chronic rejection also
      exhibited increased immunodetection of both FGFR and PCNA in mesangial and
      epithelial cells. Immunogold labeling of chronically rejected visceral epithelial
      cells revealed both cytoplasmic and nuclear/localization of FGF-1, thereby
      establishing mitogenic potential of the growth factor. The enhanced appearance of
      both biologically active FGF-1 and FGFR suggests that this polypeptide may serve
      as an important mediator of growth responses associated with glomerular lesion
      development during chronic rejection.

PMID- 8755816
TI  - Correlation of ELISA-detected IgG and IgA anti-HLA antibodies in pretransplant
      sera with renal allograft rejection.
AB  - The present study compared the occurrence of rejection episodes during the first
      twelve posttransplant (Tx) months and the 1-, 2-, and 3-year graft survivals
      among recipients stratified by the percent panel reactive antibody (% PRA) of pre
      Tx sera as detected using either an antihuman globulin determined PRA (AHG-% PRA)
      or an ELISA methodology detecting IgG reactive against soluble HLA class I
      antigens (% PRA-STAT). There was a significant correlation between AHG-PRA
      greater than or equal to 10% and a PRA-STAT greater than or equal to 10%
      (P<0.001). However, among 200 sera displaying an AHG-PRA greater than or equal to
      10% (mean 57 +/- 2l%), only 69% (138/200) displayed a PRA-STAT greater than or
      equal to 10%. With further study the discrepant finding, of 62 sera that were AHG
      PRA greater than or equal to 10% but PRA-STAT <10%, was due to the presence of
      IgM and/or IgG non-MHC reactivity. In contrast, among 293 sera displaying an AHG
      PRA < 100% (mean 3 +/- 2%), 15% (43/293) displayed a PRA-STAT greater than or
      equal to 10%. There was no correlation between AHG-% PRA and rejection episodes
      occurring during the first twelve post Tx months. In contrast, however, there was
      a highly significant correlation between PRA-STAT greater than or equal to 10%
      and the occurrence of rejection episodes during the first twelve post-Tx months
      (P < 0.001). Patients with PRA-STAT greater than of equal to 10% experienced a
      70% rejection frequency compared with the 35% rejection frequency for patients
      with PRA-STAT sera < 10% (P<0.001). A significant correlation was observed
      between the presence of IgG-1 and rejection (P<0.01) but not IgG-subclasses 2, 3,
      or 4. Of particular interest was the observation in 11 patients that the presence
      of ELISA-detected IgA anti-HLA class I antigen (ELISA-IgA PRA greater than or
      equal to 10%) was associated with a significantly reduced rejection risk compared
      with sera where only PRA-STAT greater than or equal to 10% was present (27% vs.
      70% incidence of rejection episodes, P<0.01). Finally, patients displaying
      pretransplant PRA-STAT results < 10% experienced significantly improved l-, 2-,
      and 3- year graft survivals of 85% vs. 74%, 82% vs. 70% and 81% vs. 67%,
      respectively (P<0.01 for each time point), compared with patients displaying PRA
      STAT results greater than or equal to 10%. These data suggest that the use of the
      ELISA methodology to detect IgG reactivity against soluble HLA class I antigens
      (PRA-STAT) may allow for the determination of a more clinically informative % PRA
      than the AHG-% PRA. Moreover, the presence of ELISA-detected IgA anti-HLA may act
      to inhibit rejection mechanisms associated with ELISA-detected IgG anti-HLA
      greater than or equal to 10%.

PMID- 8755817
TI  - The repetitive histologic pattern of vascular cardiac allograft rejection.
      Increased incidence associated with longer exposure to prophylactic murine
      monoclonal anti-CD3 antibody (OKT3).
AB  - While vascular cardiac allograft rejection increases morbidity and mortality
      following transplantation, factors predisposing to its development have not been
      completely elucidated. To evaluate the influence of the duration of early
      rejection prophylaxis with the murine monoclonal anti-CD3 antibody (OKT3) on the
      development of a repetitive histologic pattern of vascular cardiac allograft
      rejection, endomyocardial biopsies from 344 heart transplant recipients were
      prospectively evaluated. The influence of clinical characteristics was assessed.
      Eighty-three patients (24%) developed and 261 patients (76%) did not develop a
      repetitive histologic pattern of vascular cardiac allograft rejection. The
      vascular rejection pattern was more common in patients with a positive crossmatch
      (89% versus 11%, P<0.0001) and OKT3 sensitization (73% versus 27%, P<0.0001), and
      was positively correlated with the duration of OKT3 treatment (P<0.0001). The
      correlation persists even after excluding patients with a positive crossmatch or
      OKT3 sensitization. Patients developing a repetitive histologic pattern of
      vascular cardiac allograft rejection early after transplantation had decreased
      allograft survival (P=0.0008). The development of a repetitive histologic pattern
      of vascular cardiac allograft rejection is positively correlated with the
      duration of OKT3 treatment. Judicious use of OKT3 in early rejection prophylaxis
      in cardiac transplantation is warranted.

PMID- 8755818
TI  - Anti-skeletal muscle glycolipid antibodies in human heart transplantation as
      markers of acute rejection. Correlation with endomyocardial biopsy.
AB  - In seventeen patients the result of the histological study of 153 endomyocardial
      biopsies (EMB) was compared with the ELISA titer of anti-human skeletal muscle
      glycolipid antibodies (AGA) present in serum samples collected simultaneously
      with the EMB procedure during the first four months following cardiac
      transplantation. The glycolipids were extracted from the quadriceps femoralis of
      blood group O patients. In the serum samples corresponding to the histological
      rejection grades with myocyte necrosis (greater than or equal to 2, International
      Society for Heart and Lung Transplantation grading) the AGA titer was
      significantly higher (P<0.005) than in the less severe rejection grades. The
      follow-up in each patient showed that the AGA titer raised in the serum samples
      collected immediately after, before, or coincidentally with a histological
      diagnosis of rejection grade 2 or 3A. In only one rejection grade 3A case was a
      false-negative result observed. Determination of the cut-off of the AGA level
      versus rejection grades 2 and 3A was determined by a relative-operating
      characteristic curve. An optical density (OD) of 0.040 showed maximum efficiency
      with sensitivity 53% and specificity 79%. Four patients who had AGA with an OD
      above 0.040 at the time of transplant had a significantly higher number of
      rejection grade 2 and 3A episodes than eleven patients with low pre-transplant
      AGA titers (P<0.05). These results indicate that search of anti-skeletal muscle
      glycolipid antibodies may represent a useful noninvasive method for monitoring
      heart rejection, and suggest that its investigation prior transplant may be a
      predictor of the number of grades 2 and 3A rejection episodes.

PMID- 8755819
TI  - Biochemical and immunological evaluation of donor-specific soluble HLA in the
      circulation of liver transplant recipients.
AB  - MHC antigens, normally expressed as integral membrane proteins, are also present
      in soluble form in the peripheral circulation. These soluble human leukocyte
      antigens (sHLA) are found at elevated levels in patients with a variety of
      infections as well as in organ transplant recipients. In liver transplant
      recipients, however, most of the circulating sHLA are of donor phenotype,
      especially during the early posttransplant period. Here we report the
      purification and characterization of sHLA of both recipient and donor origin from
      liver transplant recipients. It was observed that sHLA consisted of four major
      polypeptides having molecular mass of 44, 41, 35-37, and 12 kD complexed with IgM
      and IgG antibodies. Further analysis revealed that these immunoglobulins
      contained anti-HLA antibodies. Analysis of the affinity-purified materials by a
      number of approaches failed to detect any other fragment(s) of HLA class I heavy
      chain polypeptides smaller than 12 kD. No significant difference was observed in
      the biochemical nature of the sHLA of donor and recipient origin and they were
      similar to those found in normal individuals. Affinity-purified HLA-A3 inhibited
      the cytolytic activity of an HLA-A3-specific CD8+ T cell line, whereas, purified
      sHLA-A2 failed to inhibit anti-HLA-A3 CTL activity. Further, the proliferation of
      the T cell line was not inhibited by sHLA-A3. Thus, the inhibitory activity shown
      by sHLA was antigen-specific and directed against a functional subset of T
      lymphocytes. These results support the notion that sHLA may play an important
      regulatory role in the immune response to allograft in humans.

PMID- 8755820
TI  - Is a clinical application of hybrid liver support systems limited by an initial
      disorder in cellular amino acid and alpha-keto acid metabolism, rather than by
      later gradual loss of primary hepatocyte function?
AB  - The in-vitro amino acid (AA) and alpha-keto acid (KA) metabolism of bioreactors
      initially seeded with 2.5 x 10(9) pig hepatocytes was investigated with a
      perfusion technique. Considerable changes in the culture medium concentrations of
      AA and KA were measured during the first days in culture. This is indicative of
      dynamic cellular metabolism in the initial phase. While the concentration of
      pyruvate decreased starting on the first day, alpha-ketoglutarate, alpha
      ketoisocaproate, alpha-ketoisovalerate, and alpha-keto-beta-methyl-n-valerate
      were synthesized. The long term use of hepatocyte cultures in bioreactors and
      thus a desirable clinical hybrid liver support therapy appears to be possible
      since the hepatocytes switched, after 15 days in culture, to steady-state
      conditions with a stable amino acid turnover featuring general AA uptake
      accompanied by KA release. The release of branched chain KA, in particular that
      of alpha-ketoisocaproate, reflects an effective transamination activity in the
      bioreactor system. Primary pig hepatocytes cultivated in hybrid liver support
      systems for therapy of acute liver failure or as devices for bridging to liver
      transplantation can sustain amino acid metabolism for at least 30 days in vitro.
      However, an initial disorder following the cell isolation that is demonstrated
      may limit immediate utilization of the systems prior to the reorganisation of the
      cells to tissue-like structures in bioreactors.

PMID- 8755821
TI  - Transfusion of polarized TH2-like cell populations into SCID mouse cardiac
      allograft recipients results in acute allograft rejection.
AB  - It has been hypothesized that TH1 cells mediate the archetypical cell-mediated
      immune response of acute allograft rejection, whereas TH2 cells promote allograft
      acceptance. To test this, we transfused SCID cardiac allograft recipients with
      polarized TH1-like or TH2-like graft-reactive T cells, and monitored graft
      function and graft-reactive immune responses in the graft recipients. Polarized
      THl-like cells, which were generated in vitro by stimulating syngeneic
      splenocytes with donor alloantigens in the presence of anti-IL-4 mAb, produced
      IFNg but not IL-4 when restimulated with donor alloantigen. Polarized TH2-like
      populations, which are generated in vitro by stimulating syngeneic splenocytes
      with donor alloantigens in the presence of IL-4, produced IL-4 but not IFNg when
      restimulated with donor alloantigen. Interestingly, bioassays of culture SN from
      restimulated TH1 but not TH2 cells revealed IL-2 production, although LDA
      analyses revealed that the TH1 and TH2 cells had identical frequencies of IL-2
      producing cells. Transfusion of THl-like cells into SCID cardiac allograft
      recipients resulted in acute rejection within 7-10 days that was characterized by
      cellular infiltration, myocyte necrosis, and edema. Graft-infiltrating cells
      (GIC) recovered from TH1-transfused animals contained large numbers of graft
      reactive IL-2-producing cells (68-269/10(6) GIC), but no LDA-detectable IL-4
      producing cells. These data support the hypothesis that donor-reactive TH1 cells
      can promote acute allograft rejection. In contrast to the hypothesis, transfusion
      of the polarized TH2-like population into SCID cardiac allograft recipients also
      resulted in histologically similar acute rejection within 7-10 days. Infiltrating
      cells recovered from TH1-transfused allografts contained large numbers of graft
      reactive (109-1458/10(6) GIC), LDA-detectable, IL-4-producing cells--indicating
      that the TH2 cells had arrived at the graft-but promoted acute allograft
      rejection rather than allograft acceptance.

PMID- 8755822
TI  - Acyclovir triphosphate inhibits the diagnostic polymerase chain reaction for
      cytomegalovirus.
AB  - Immunocompromised patients are frequently treated with guanine analogs such as
      acyclovir and ganciclovir. Acyclovir triphosphate, the active intracellular
      metabolite of acyclovir, exerts its antiviral effect by inhibiting herpesviral
      DNA polymerases through premature chain termination. PCR has recently been used
      for early detection of cytomegalovirus. However, we and others have experienced
      false-negative results for cytomegalovirus-PCR in patients on both acyclovir and
      ganciclovir. The impact of these agents on PCR assay is unknown. In an attempt to
      investigate the role of guanosine analogs in these false-negative results, we
      exposed the DNA-PCR for murine beta-actin, a murine CMV IE gene sequence, and a
      human CMV IEA1 product, to phosphorylated acyclovir derivatives. Varying
      concentrations of acyclovir-5'-triphosphate (final: 70-6000 microM) in the
      reaction mix resulted in an absence of detectable product at or above 490-670
      microM. Inhibition was not observed with up to 1400 microM acyclovir
      monophosphate. Increasing the Taq concentration to 10 units/100 microL stopped
      the inhibition. Our data demonstrate that acyclovir-5'-triphosphate inhibits PCR
      amplification of various gene products in a concentration-dependent manner.
      Furthermore, this inhibition appears to be specifically directed against the Taq
      polymerase and can be completely reversed by higher concentrations of the enzyme.
      Thus, false-negative PCR results for a viral gene product in patients under
      prophylaxis/treatment with acyclovir could potentially be due to contamination by
      acyclovir triphosphate. Therefore, negative PCR results in these patients need be
      interpreted with caution.

PMID- 8755823
TI  - Increased expression of interferon-gamma in a rat model of chronic intestinal
      allograft rejection.
AB  - Chronic rejection remains a major cause of late graft dysfunction. Although much
      research has focused on acute rejection, little is known about the mechanisms of
      chronic rejection. Our group has recently reported evidence of significant
      intestinal smooth muscle hypertrophy and hyperplasia associated with abnormal
      contractile and electrical activities in a rat model of chronic intestinal
      rejection. The changes in the smooth muscle layer are associated with a
      significant inflammatory infiltrate. In order to further delineate the immune
      mechanisms of chronic rejection, we sought to clarify the nature of this
      infiltrate. Orthotopic small bowel transplantation was performed using an
      allogeneic (ACI-Lewis) rat combination. The rats only received immunosuppression
      for the first 28 days posttransplantation (cyclosporine 15 mg/kg daily from
      postoperative day 0 to 6 and every other day from postoperative day 7 to 28).
      This led to chronic rejection of the graft by day 90, at which time the rats were
      sacrificed. Analysis by immunohistochemistry revealed NK and CD5+ leukocytes
      infiltrating the muscular layer. Examination of cytokine production by
      radiolabeled polymerase chain reaction showed high levels of steady state
      interferon-gamma mRNA in full thickness intestinal segments and within the
      isolated muscularis of chronically rejecting intestinal allografts as compared to
      syngeneic and control grafts. Interferon-gamma mRNA was localized to both the
      muscularis and mucosa. Interestingly, positively hybridized cells within the
      muscularis tended to preferentially localize to the myenteric and submucosal
      plexuses suggesting potential role for this cytokine in chronic intestinal
      ejection.

PMID- 8755824
TI  - CD2 antigen targeting reduces intragraft expression of mRNA-encoding granzyme B
      and IL-10 and induces tolerance.
AB  - We explored the hypothesis that CD2 antigen-specific therapy would reduce
      intragraft gene expression and facilitate the emergence of transplantation
      tolerance. This postulate was tested in a murine pancreatic islet cell allograft
      model in which a novel mAb directed at the CD2 antigen, RM2-2 anti-CD2 mAb (RM2-2
      mAb), was used to regulate CD2 antigen-dependent antiallograft response.
      Peritransplant administration (day -1, 0, and day + 1 with respect to
      transplantation) of RM2-2 mAb resulted in significantly longer survival of DBA/2
      pancreatic islet cell allografts in the B6AFl recipient compared with untreated
      recipients. RM2-2 mAb therapy facilitated the induction of antigen-specific
      tolerance: whereas retransplantation with the original donor strain (DBA/2) islet
      cell allograft was successful, retransplantation with a third-party donor (SJL)
      islet cell allograft was not. In vivo administration of RM2-2 mAb therapy
      resulted in a decrease in the percentage of T cells that coexpressed the CD2
      antigen (demonstrated by two-color flow cytometry) and in a decrease in
      intragraft expression of cytotoxic cell specific granzyme B mRNA and IL-10 mRNA
      (detected by RT-PCR). Our data, in addition to demonstrating for the first time
      the efficacy of RM2-2 anti-CD2 mAb, suggest that CD2 antigen is a suitable target
      for the induction of transplantation tolerance.

PMID- 8755825
TI  - Inhibition of anti-Gal IgG binding to porcine endothelial cells by synthetic
      oligosaccharides.
AB  - Rejection of pig-to-human or pig-to-primate xenografts is mediated by the natural
      anti-Gal antibody, which interacts with alpha-galactosyl epitopes (i.e., Gal
      alpha1-3Gal beta1-4GlcNAc-R) abundantly expressed on porcine cells. The objective
      of this study was to determine the ability of various synthetic oligosaccharides
      to inhibit the binding of anti-Gal IgG molecules to porcine endothelial cells in
      vitro. Such inhibition ultimately may help to reduce or to prevent the in vivo
      antibody-dependent cell cytotoxicity (ADCC) reaction. In the absence of
      complement-mediated hyperacute rejection, the ADCC induced by anti-Gal IgG
      molecules is likely to cause the chronic rejection of xenografts. The synthetic
      free alpha-galactosyl epitope (Gal alpha1-3Gal beta1-4GlcNAc) was found to be 300
      fold more effective than melibiose or alpha-methyl galactoside in inhibiting anti
      Gal binding to porcine endothelial cells, and to prevent >90% of the antibody
      binding at a concentration of 1 mM. The disaccharide Gal alpha1-3Gal was ten-fold
      less effective than the free alpha-galactosyl epitope. Accordingly, the affinity
      of the disaccharide to anti-Gal, as measured by equilibrium dialysis, was seven
      fold lower than that of the trisaccharide. The effective concentration of
      oligosaccharides inhibiting anti-Gal is independent of the antibody affinity, but
      is dependent on the concentration of the antibody. Based on the small difference
      in affinity between Gal alpha1-3Gal beta1-4GlcNAc and Gal alpha1-3Gal beta1-4GIc,
      and the large difference in the price of N-acetyllactosamine vs. lactose, it is
      suggested that lactose may be considered as an appropriate starting material for
      synthesizing large amounts of a trisaccharide that effectively neutralizes anti
      Gal.

PMID- 8755826
TI  - The significance of timing of additional short-term immunosuppression in the
      donor-specific transfusion/cyclosporine-treated rat.
AB  - It is hypothesized that the mechanism, or mechanisms, responsible for donor
      specific transfusion (DST)/cyclosporine (CsA) immunosuppression is generated by
      an active immune response that is most dynamic in the immediate peritransplant
      period and thus might be at the peak of vulnerability to the influences of added
      immunosuppression. To better define this concept, four immunosuppressive drugs
      were combined with a d-1 DST and 14-day course of CsA in the ACl-to-Lewis cardiac
      transplant model. A 5-day course of antithymocyte globulin (ATG) initiated at d-1
      or d+4 with DST/CsA reduced survival vs. DST/CsA alone (27.0 +/- 2.6 days and
      24.6 +/- 5.7 days vs. 95.3 +/- 16.3 days, P<.05). Delay of initiation to d+7
      improved survival to 39.5 +/- 8.9 days. A 5-day course of methylprednisolone (MP)
      begun at d-1 with DST/CsA decreased survival vs. DST/CsA alone, 59.2 +/- l0.0
      days vs. 95.3 +/- 16.3 days, but delay to d+4 improved survival to 110 +/- l8
      days, P<.05 vs d-1. A 3-day course of brequinar (Breq) begun at d-1 with DST/CsA
      increased survival to 244 +/- 48.6 days, while delay to d+4 reduced survival to
      49.0 +/- 6.7 days, P<.05 vs. d-1. Finally, a 5-day course of rapamycin (Rapa),
      was given with d-1 DST/CsA treatment beginning on d-1, d0, d+l, d+3, d+5, and
      d+7. In this instance, no significant differences in survival were found between
      timing groups or DST/CsA control. Together, these data support the hypothesis
      that DST/CsA treatment generates an active immune response that is inhibited by
      early initiation of ATG or MP, enhanced by early administration of Breq, and
      unchanged by early administration of Rapa.

PMID- 8755828
TI  - The frequencies of HLA alleles and haplotypes and their distribution among donors
      and renal patients in the UNOS registry.
AB  - HLA allele and haplotype frequencies are used in transplantation, anthropology,
      forensic medicine, and studies of the associations between HLA factors and the
      immune response. The cost of determining these frequencies through family studies
      can be avoided by estimating them from population data. We have utilized the data
      in the UNOS donor registry and kidney transplant waiting list to estimate allele
      and haplotype frequencies for the HLA-A, -B, and -DR(B1) loci and report the
      allele and a portion of the haplotype data here. Using programs written in A
      Program Language (APL) we were able to perform all analyses on a personal
      computer. We have found that the distribution of haplotype frequencies varies
      among the races, with Caucasians having a greater number of both more common and
      extremely rare haplotypes. Despite the sizes of the groups studied, only one
      third to two-thirds of the haplotypes theoretically possible were actually
      observed. Although the data confirm the well-known fact that the distributions of
      alleles and haplotypes varies among races, they also reveal that certain common
      haplotypes are shared among all racial groups and represent an opportunity for
      well-matched transplants between donors and recipients of different races.

PMID- 8755827
TI  - Characterization of T cell receptor beta chains of accumulating T cells in skin
      allografts in mice.
AB  - The study of T cells involved in the immune reaction that occurs in engrafted
      organs should provide information that would be helpful in the regulation of
      allograft rejection in organ transplantation. Toward this end, we focused on
      detection and characterization of accumulating T cells in mouse skin allografts
      from B10.A(4R) to C57BL/6 mice in vivo. T cell receptor beta genes were amplified
      by reverse transcriptase-PCR from mRNA of the skin grafts, and accumulating T
      cell receptor beta gene clonotypes were identified by their single strand
      conformation polymorphism. Their joining region usage and the amino acid
      sequences of the complementarity-determining region-3 were then determined. The
      results were as follows: (1) Distinct oligoclonal accumulation of T cells was
      more prevalent in the skin allografts than in the syngenic skin grafts. (2)
      Although the accumulating T cell clonotypes appeared to use many different
      variable-region gene families, preferential combinations of variable region
      joining region were found. (3) Several homologous amino acid sequences were found
      in these accumulating TCR beta genes in allografts, suggesting that these T cells
      are driven by the same or similar antigens. (4) In addition, little T cell
      accumulation was found in spleens from the mice with allografts or syngenic skin
      grafts. Taken together, accumulating T cells in the skin allografts were detected
      in vivo, and some appeared to have characteristics in common. This may lead to T
      cell clonotype-specific therapy in organ transplantation.

PMID- 8755829
TI  - The preferential cytolytic T lymphocyte response to immunodominant minor
      histocompatibility antigen peptides.
AB  - C57BL/6 mice preferentially generate cytolytic T lymphocytes (CTL) to a limited
      number of immunodominant minor antigens and associated immunogenic peptides when
      primed with H2-matched Balb.B spleen cells despite multiple minor
      histocompatibility (H) antigen differences. We have examined the complexity of
      dominant H antigens recognized by these CTLs to estimate the number of peptides
      associated with single antigens. Peptides eluted from Kb molecules of
      lymphoblasts from Balb.B and CXB recombinant inbred (RI) strains were tested for
      sensitization of RMA-S cells for lysis by short-term C57BL/6 CTL lines specific
      for Balb.B and CXB strains. Anti-Balb.B CTLs recognized four Kb-bound peptides;
      subsets of these peptides were recognized by anti-CXB CTLs when tested with
      peptides from the respective CXB strains. Single peptides segregated
      independently among the CXB strains, confirming that single peptides were encoded
      by independently segregating alleles. These peptides were expressed in diverse
      inbred mouse strains and were recognized preferentially by C57BL/6 CTLs
      stimulated by different inbred mouse strains. This set of peptides was
      subclassified by their capacity to sensitize targets when presented in
      unfractionated mixtures of Kb-bound peptides. The peptide associated with the
      previously classified dominant CTT-2 antigen was the only peptide to strongly
      sensitize RMA-S cells for lysis under these conditions. These results suggest
      that dominant peptides have a wide strain distribution and may have a distinct
      advantage over dominated peptides in binding to class I molecules and/or in
      presentation to CTLs.

PMID- 8755830
TI  - Fifty-percent partial liver transplantation in the rat.
AB  - Reduced-size liver transplantation in the rat has been useful in the study of
      hepatic regeneration. We describe a modified technique for partial liver
      transplantation in the rat using a 50% reduced-size graft. Male Lewis rats
      (RT1(1)), weighing 250 to 280 g, were used as donors and recipients. The
      harvested donor liver was placed in 4 degrees C cold saline and graft reduction
      was performed ex situ by resecting the left lateral lobe, the left portion of the
      median lobe, and the caudate lobes. The reduced graft was composed of the right
      portion of the median lobe and the right lobe, weighing 5.33 +/- O.58 g (53.6 +/-
      2.2% of the donor liver before reduction, n=7). The recipient 1-week survival
      rate was 85.7%. The use of reduced livers permits the study of host responses to
      a deficient graft. This technique provides another choice of liver volume to be
      implanted and allows the study of regeneration of small-for-size livers more
      precisely in combination with more extensive graft reduction.

PMID- 8755831
TI  - Fulminant hepatic failure from the Budd-Chiari syndrome. A bridge to
      transplantation with transjugular intrahepatic portosystemic shunt.

PMID- 8755832
TI  - The long-term virologic and pathologic impact of renal transplantation on chronic
      hepatitis B virus infection.
AB  - In an attempt to evaluate the long-term reciprocal impact of renal
      transplantation on hepatitis B virus infection, we analyzed the clinical,
      virologic, and pathologic features of 151 HBsAg-positive kidney transplant
      recipients. The spontaneous disappearance rates of HBsAg, HBeAg, and HBV DNA
      during a median follow-up of 125 months (range 1 to 320) were 3, 30.6, and 3%,
      respectively, figures lower than in the general population. A high rate of
      persistent viral replication (50%) and reactivation (30%) was noted. Noteworthy
      was the high frequency of histologic deterioration (85.3%), accompanied by
      cirrhosis in 28% and by hepatocellular carcinoma in 23% of the patients with
      cirrhosis. Co-infection by hepatitis C and B viruses was significantly associated
      with histologic worsening. Liver disease was the leading cause of death (36.6%),
      especially in patients with cirrhosis. Despite persistent viral replication,
      histopathologic deterioration, and liver-related overmortality, there were
      paradoxically no significant differences in the survival of these 151 HBsAg
      positive compared with 1247 HBsAg-negative kidney recipients--however, allograft
      actuarial survival was better in the former than in the latter group (P=0.0006).
      Chronic hepatitis B infection is not a contraindication to renal transplantation
      in the absence of cirrhosis. The presence of cirrhosis should lead either to
      dialysis continuation or to a combined liver/kidney transplantation, in the
      absence of viral replication.

PMID- 8755833
TI  - Acute rejection of cardiac allografts by noncytolytic CD4(+) T cell populations.
AB  - Cytolytic T cells were generated in vitro by culturing purified Balb/c CD4+ T
      cells with irradiated C57Bl/6 (B6) splenocytes plus anti-IL-4 mAb. Matched,
      noncytotoxic T cells were similarly generated by culturing purified Balb/c CD4+ T
      cells with irradiated B6 splenocytes plus recombinant murine IL-4. The latter T
      cells displayed to cytolytic activity, even in lectin-mediated lysis assays, but
      produced characteristic cytokines upon contact with specific alloantigens.
      Transfusion of cytolytic T cell populations into Balb/c SCID mice bearing B6
      cardiac allografts resulted in acute allograft rejection within 5 to 10 days.
      Transfusion of noncytolytic T cell populations into Balb/c SCID mice bearing B6
      cardiac allografts also resulted in acute allograft rejection within 7 to 10
      days. Limiting dilution analysis (LDA) of infiltrating cells recovered from
      rejected allografts after collagenase digestion demonstrated that the CD4+ T
      cells retained their cytolytic or noncytolytic functional phenotypes in vivo
      throughout the rejection process. These data demonstrate that isolated CD4+ T
      cell populations can promote rapid acute cardiac allograft rejection, and that
      cytolytic activity is not necessary for this acute rejection response.

PMID- 8755834
TI  - [The effects of long-term treatment of sotalol hydrochloride on time and
      frequency domain parameters of signal averaged electrocardiogram in patients with
      ischemic heart disease].
AB  - The aim of this study was to assess the influence of sotalol hydrochloride on
      time- and frequency-domain parameters of signal-averaged electrocardiogram
      (SAECG) in patients with ischemic heart disease (IHD). The study population
      consisted of 25 patients (16 women and 9 men), mean age 56.6 +/- 8.3. Sotalol was
      orally used in dose 160 mg/day during 6 weeks. Recording of SAECG and ambulatory
      Holter monitoring were made at baseline and in 10 day and after 6 weeks of
      therapy. The following time-domain parameters were analyzed: the root mean square
      voltage of the last 40 and 50ms of the filtered QRS (RMS 40 i RMS 50), total time
      duration of filtered QRS (t-QRS) and duration of low amplitude signals < 40
      microV in the terminal part of QRS (LPD). Late potentials (LP) were recognized
      when at least two from three criteria were fulfilled: 1) RMS40 < 20 microV, 2) t
      QRS > 114 ms, 3) LPD > 38ms. Frequency analysis of SAECG allowed to calculate the
      following parameters in logarithmic scale: energy spectrum > -60dB (A) and
      decibel drop at 40 Hz (Dd) and also in linear scale: area ratio 20-50/0-20 Hz
      (Ar) and magnitude ratio (MR1-7). The values of RMS40 and RMS50 and also t-QRS
      and LPD did not significantly change after sotalol treatment. At baseline the
      presence of LP was recorded in 7 (28%) cases, after 10 days of antiarrhythmic
      therapy only in 3 (12%), and after 6 weeks occurred in 6 (24%) cases. Moreover,
      sotalol hydrochloride did not statistically significant change frequency-domain
      parameters in logarithmic scale: A and Dd. On the other hand, the parameters in
      linear scale: MR1, MR4 and MR6 significantly change but these changes were not
      uniform. These findings suggest that oral treatment of sotalol hydrochloride did
      not significantly change time- and frequency-domain parameters of signal-averaged
      electrocardiogram in patients with ischemic heart disease.

PMID- 8755835
TI  - [The influence of amiodarone on results of the signal-averaged
      electrocardiogram].
AB  - The aim of this study was to assess if amiodarone hydrochloride administered
      intravenously influenced signal-averaged electrocardiogram and if this effect can
      be used in diagnosing patients prone to sustained ventricular tachycardia (sVT).
      Two hundred thirty seven patients were divided into 3 groups: group K--58
      patients with no apparent heart disease, group W--121 patients with remote
      myocardial infarction and group C-58 patients with remote myocardial infarction
      and at least one episode of sVT. Signal-averaged electrocardiograms (SAECG) were
      assessed in time domain (QRS, LPD, RMS40) and frequency domain analysis
      logarhythmically (40 D, 60 A) and linearly [formula: see text] for windows
      lasting 120 and 140 ms, and starting 20, 40, 80 ms before the end and 60 ms after
      the beginning of QRS complex. Amiodarone hydrochloride increased frequency of
      late potentials (LP) in all groups especially in group C (K 5.2%-9.1%, W 33.9%
      41.4%, C 75.9% -90.9%. Amiodarone hydrochloride prolonged total activation time-
      QRS (K -4.27 ms, W -6.06 ms, C -5.82 ms), time of low amplitude signals LPD (K 
      2.64 ms, W -2.87 ms, C -5.39 ms) and decreased the amplitude of RMS40 (K -2.12
      mV, W -4.67 mV, C -5.0 mV). In group C the influence of amiodarone hydrochloride
      was found the strongest in the terminal part of the QRS complex whereas its
      influence on total activation time of QRS complex was weaker. We concluded that
      in patients prone to sVT amiodarone hydrochloride most strongly influenced the
      terminal part of QRS complex which suggested predominant influence on the zone of
      delayed conduction and amiodarone hydrochloride non significantly influenced on
      the results of frequency domain analysis.

PMID- 8755836
TI  - [Comparison of the ability to control anemia in patients on hemodialysis and
      peritoneal dialysis considering iron reserves and plasma erythropoietin].
AB  - It is known, that patients undergoing CAPD have less severe anaemia than those
      receiving hemodialysis (HD). In addition they require smaller doses of rHuEpo to
      control anaemia than HD pts. We have decided to compare plasma erythropoietin
      (pEpo) and iron reserves (IR) in these both groups of pts. 17 pts on CAPD and 50
      pts on HD were diagnosed. 35% pts on CAPD and 52% pts on HD required permanent
      rHuEpo treatment to maintain hemoglobin (Hb) concentration above 9.5g/dl and Ht
      above 30%. Plasma EPO and ferritin levels were measured by enzymatic immunoassay.
      IR were estimated by formula: IR = 400x [ln (ferritin) - ln(50)]. Compared to
      CAPD, HD pts had higher IR (405 +/- 76 vs. 358 +/- 120 mg) but differences are
      not statistically significant. Plasma Epo level (geom. mean) was statistically
      significant higher p = 0.025 in HD pts compared to CAPD pts (8.68, range 2-53 vs.
      5.21 range 2-15 mV/ml) Hb concentrations did not differ significantly between pts
      on CAPD and HD. CAPD pts controlled anaemia better than HD pts despite lower
      concentration of endogenous erythropoietin.

PMID- 8755837
TI  - [Circadian rhythm of lutropin and follitropin in patients with chronic renal
      failure].
AB  - Dysfunction of the hypothalamic-pituitary-gonadal axis in patients with chronic
      renal failure is well documented. This study was aimed to answer the following
      questions: 1. Is there the circadian rhythm in serum concentration of lutropin
      and follitropin preserved in male patients with chronic renal failure. 2. Does
      hemodialysis, used in treatment of uremia, influence LH and FSH circadian
      variations. 3. Is there statistically significant difference between hormonal
      circadian rhythm determined on the day of hemodialysis and on the interdialytic
      day. Circadian patterns of LH and FSH and their characteristics were studied in
      32 uremic men and 16 healthy men. 16 uremic males were non-dialyzed and 16 were
      hemodialyzed. In all investigated cases the basal serum concentrations of LH and
      FSH were measured 8-times a day at 3-hour intervals. LH and FSH serum
      concentrations were determined using an immunoradiometric assay. To estimate the
      circadian rhythms of the investigated hormones COSINOR computer analysis was
      used. The following results were obtained: 1. Significantly higher basal LH
      concentration in hemodialyzed patients, compared with the control group. 2.
      Absence of significant differences in LH serum concentration between hemodialyzed
      patients (on the day of dialysis and on the following day) and non-dialyzed
      patients. 3. Absence of LH circadian rhythm in both non-dialyzed and hemodialyzed
      uremic patients. 4. Existence of LH circadian rhythm in healthy subjects. 5.
      Significantly higher serum FSH concentration in hemodialyzed patients compared
      with healthy subjects.

PMID- 8755838
TI  - [Evaluation of arterial blood pressure and heart rate during exercise tests in
      patients with essential hypertension in different stages of hypertension].
AB  - This article analyses the changes of arterial blood pressure and heart rate (HR)
      in 120 patients with essential hypertension during two successive exercise tests.
      Before and during the tests, the patients did not take any hypertensive drugs.
      The obtained measuring results at exercise tests and restitution were the basis
      for the calculating regression equations. Then the results were analyzed
      statistically (p < 0.05) and clinically (drop or increase of arterial systolic
      blood pressure value (SAP) or/and diastolic (DAP) by 5 mmHg, and HR by 5 beats
      per minute). The HR response was comparable in both test for all tested groups
      both in exercise and restitution periods. For the additional sex division the HR
      value in all subgroups women was lower in the second test and satisfies the
      condition of statistic and clinical significance. In the second test SAP was
      lower only in the group of mild pressure and in the group without organ changes
      (stage I WHO) during exercise. At restitution periods the SAP values were lower
      in all the tested groups with the exception of the group with borderline
      hypertension. DAP was lower in the second test in all the tested groups both in
      exercise test and in the restitution period. It is also shown that the quantity
      of DAP difference in the second test is the greater, the higher value of DAP at
      restitution is.

PMID- 8755839
TI  - [Significant negative correlation between fasting plasma insulin and ambulatory
      blood pressure in patients on chronic hemodialysis].
AB  - Positive correlation between blood pressure and insulin is well established in
      patients with essential hypertension. The aim of the present study was to examine
      the relationship between fasting plasma insulin level and ambulatory blood
      pressure (ABPM) in patients with chronic renal failure. The study group consisted
      of 20 patients (11 females, 9 males, mean age 39 +/- 12 years) on chronic
      haemodialysis (mean 2.5 years). Fasting plasma insulin (FPI) was measured by
      radioimmunoassay. The patients were investigated before and after haemodialysis.
      FPI significantly increased after haemodialysis from 18.4 +/- 12.0 to 40.1 +/-
      31.9 mIU/l (p < 0.01), while creatinine concentration decreased from 1158 +/- 130
      to 910 +/- 159 mumol/l (p < 0.001). Night-time systolic blood pressure (SBP) was
      significantly lower during the day of haemodialysis (141.9 +/- 19.6 mmHg vs. 136
      +/- 27.7 mmHg, p < 0.05). 24-hour and daytime SBP was nonsignificantly lower
      after haemodialysis. 24-hour diastolic blood pressure (DBP) was significantly
      lower during the day of haemodialysis (92.9 +/- 12.5 mmHg vs. 87.3 +/- 14.3 mmHg,
      p < 0.05), as well as daytime (94.9 +/- 12.1 mmHg vs. 88.8 +/- 14.6 p < 0.05) and
      night-time DBP (88.9 +/- 16.0 mmHg vs. 83.8 +/- 17.4 mmHg p < 0.05). FPI was
      found to be significantly negatively correlated with 24-hour, daytime and night
      time SBP on the day of haemodialysis (r = -0.63, p < 0.005; r = 0.64, (p < 0.005
      and r = -0.54, p < 0.05, respectively). The significant negative correlation
      between FPI and 24-hour SBP suggests that insulin could reveal its hypotensive
      effect after the haemodialysis.

PMID- 8755840
TI  - [Selected diagnostic and clinical aspects of chronic viral hepatitis type C].
AB  - The aim of this study was to evaluate selected diagnostic and clinical aspects of
      chronic hepatitis C (CH-C) in the group of 80 patients: 68 males aged 24-65 (mean
      39.8 +/- 10,5) and 12 females aged 35-66 (mean 48.7 +/- 12.6). The
      epidemiological data allowed to divide the basic group into 3 subgroups: patients
      with transfusion-associated CH-C (subgroup I: 12 males, mean age 38 +/- 6.7 and 2
      females aged 40 and 46), CH-C patients with parenteral hepatitis C virus exposure
      other than blood transfusion (subgroup II: 25 males, mean age 40.6 +/- 8.2 and 5
      females aged 43 +/- 15.1) and sporadic cases with unknown HCV exposure (subgroup
      III: 31 males, mean age 38.2 +/- 11.2 and 5 females, mean age 50.5 +/- 10.3). The
      duration of the disease (CH-C) was calculated from the incident of acute viral
      hepatitis or the first signs of liver damage caused by HCV to the confirmation of
      CH-C by liver biopsy. The following data were analyzed: a frequency of acute
      viral hepatitis with jaundice at the beginning of the disease, ALT flare-ups,
      mean highest activities of ALP and GGT, frequency of hypergammaglobulinaemia and
      sings of fatty liver in ultrasonographic finding (USG). In all patients but one
      anti-HCV antibodies (ELISA 2nd generation test by Abbott) were detected. In 64/80
      subjects antibodies to HCV antigens: 5-1-1, C 100-3, C 33c and C 22 were
      determined by RIBA-2 test (Ortho). In 62/80 patients HCV-RNA in serum was
      determined by RT PCR. Liver biopsy was performed in 71/80 patients. Other co
      existent liver diseases were excluded. The similarity between 3 subgroups was
      shown: similar percentage of males and females, similar patients mean age and the
      duration of the disease. It was shown that the acute beginning of the disease
      with jaundice has been observed twice as frequent in subgroups I and II compared
      with subgroup III. The same frequency of ALT flare-ups in all subgroups was
      observed (25-28.6%). No differences in mean highest ALP and GGT activities in 3
      subgroups were observed. It was shown, however, that hypergammaglobulinaemia was
      detected more frequently in subgroup III (30.5%) compared with subgroup I (7.1%)
      and II (16.7%). The signs of fatty liver in ultrasonographic findings were also
      observed more frequently in subgroup III (30.5%) than in subgroup I (14.3%) or II
      (16.7%). In all patient but one, in which anti-HCV antibodies by ELISA test were
      detected, anti-C 33c and anti-C 22 antibodies by RIBA were present. HCV-RNA in
      serum was detected in 77.8% subjects from subgroup I. 73.9%-from subgroup II and
      66.7%-from subgroup III. In all HCV-RNA positive patients anti-HCV antibodies
      were detected. The evidence of chronic active hepatitis confirmed by liver biopsy
      was shown in 63.6%, 67.8% and 71.8% of patients from subgroup I, II and III,
      respectively. In no case normal liver morphology was present. Authors concluded
      the distressing fact of the high incidence of chronic active hepatitis in
      patients unaware of HCV infection, without the incident of acute hepatitis at the
      beginning of the disease (over 1/3 of all described subjects). The differences of
      the clinical course of the disease between subgroups 1 + II and subgroup III
      suggest two different routes of HCV infection or the presence of two different
      HCV mutants in Polish population. Authors emphasise the necessity of HCV gene
      typing in CH-C patients, which might explain the surprisingly high incidence of
      chronic active hepatitis in the reported group. The use of the presented data for
      the general practitcioner making the diagnosis of crytogenetic liver disease is
      also accentuated.

PMID- 8755842
TI  - [Intraperitoneal use of human tumor necrosis factor (hrTNFalfa) in patients with
      ascites during advanced neoplastic disease].
AB  - The results are presented of a clinical trial with the use of hrec TNF alpha
      administrated intraperitoneally in advanced cancer patients suffering from
      malignant ascites. Fourteen patients in a terminal phase of a neoplastic disease
      were treated with intraperitoneal infusions of hr TNF alpha in progressively
      increasing doses. The procedure was repeated maximum 8 times, with one-week
      intervals between each dose. Response to the therapy (complete or partial
      remission) was observed in 8 patients. No evidence was shown of increased
      survival time in the cancer patients receiving TNF alpha. However, the treatment
      significantly increased their quality of life, especially in its psychological
      and somatic aspects.

PMID- 8755841
TI  - [The fate of patients with diabetes mellitus after amputation of a lower limb as
      a consequence of gangrene].
AB  - The aim of study was to analyse factors that modified the survival time of 125
      patients with diabetes mellitus and 121 patients with normal tolerance glucose to
      whom amputations of a lower limb in consequence of gangrene were performed. The
      prospective study were started on 5th January 1989 and finished 31st December
      1993. Among the examined patients with NIDDM were 66 men in the age from 53 to 88
      years (mean age 66.8 +/- 8.5 (+/-SD) years) and 48 women in the age from 58 to 91
      years (mean age 71.8 +/- 9.1 years). Among the examined patients with IDDM were 6
      men in the age from 40 to 65 years (mean age 55.7 +/- 9.7 years) and 5 women in
      the age from 34 to 72 years (mean age 53.7 +/- 13.6 years). The mean duration of
      NIDDM among men was 14.1 +/- 8.6 years, among women - 13.6 +/- 10.2 years and the
      mean duration of IDDM among men was 26.1 +/- 6.7 years, among women-26.0 +/- 10.8
      years. In that period among patients with diabetes mellitus 80 patients died (64
      percent), and among patients with normal glucose tolerance-died 39 patients (32
      percent). In the analysis of survival time of patients with diabetes mellitus
      after nontraumatic amputation of a lower limb the following factors were the
      essential predictors of death: age (p = 0.0001), duration of diabetes (p = 0.03),
      arterial hypertension (p = 0.006), peripheral arterial disease (p = 0.0007),
      diabetic nephropathy (p = 0.0065). Among patients with normal tolerance glucose
      only the age was the essential predictor of death (p = 0.0001). The necessity of
      performance of amputation of a lower limb among patients with diabetes mellitus
      provides information on unsuccessful course of disease.

PMID- 8755844
TI  - [Acute pancreatitis complicated by pancreatic ascites. Diagnostic and therapeutic
      difficulties].
AB  - The authors report a case of acute pancreatitis, complicated by pancreatic
      peritoneal fistula and ascites in 26 year old man, with a history of excessive
      alcoholic intake. Biochemical investigation of ascitic and pleural fluids, which
      revealed markedly elevated activity of pancreatic enzymes and protein indicated
      their pancreatic origin. After 25 days of treatment with somatostatin and
      parenteral nutrition, the condition of the patient improved and he was dismissed
      home.

PMID- 8755843
TI  - [Diagnostic difficulties in primary hyperparathyroidism based on personal
      observations].
AB  - The primary hyperparathyroidism (PHP) is a complex of nosological symptoms
      associated with disturbances of calcium-phosphate equilibrium and bone
      metabolism, caused by excessive secretion of parathormone. In the past regarded
      as a rare entity, today it is arousing great interest due to ever more frequent
      diagnosis of it in the stage of subtle changes or in the asymptomatic period.
      Untreated PHP leads to the development of a number of organ complications, and
      even to a life-threatening state, that is hypercalcemic crisis. The authors
      discussed differential diagnostic and localisation difficulties in PHP on example
      of own observations.

PMID- 8755845
TI  - [Molecular mechanism of glucocorticoid action].

PMID- 8755847
TI  - [Polycythemia].

PMID- 8755846
TI  - [Variability of antiarrhythmic drug action in prolonging action potential
      duration during various rates of heart action].

PMID- 8755849
TI  - [Evaluation of selected parameters of zinc metabolism in patients with primary
      hypertension].
AB  - The aim of the study was to investigate the role of zinc (Zn) in essential
      hypertension (EH). PATIENTS AND METHODS: Material of the study consisted of 31
      patients (12 female, 19 male) with mild and moderate EH and 20 healthy persons
      (NT) (7 female, 13 male). Erythrocyte (ZnE) and serum (ZnS) zinc as well as 24
      hour urinary zinc excretion (ZuU) were assessed in both groups. Zn parameters
      were measured by atomic absorption spectrophotomery. RESULTS: ZnS was lower and
      ZnE was higher in EH (p < 0.001) than in normotensives. ZnU did not differ
      between EH and NT. ZnE and ZnS negatively correlated with age in NT but not in
      EH, ZnU negatively correlated with age only in EH. BP positively correlated with
      ZnS in EH but not in NT. In both groups negative correlations were found between
      BP and ZnU. CONCLUSIONS: 1. Zinc probably plays a role in pathogenesis of
      essential hypertension.

PMID- 8755848
TI  - [Evaluation of blood rheology indices in patients with pheochromocytoma].
AB  - Investigated group consisted of 28 patients (21 female and 7 male) with
      pheochromocytoma in mean age of 39.9 +/- 13 years, while control group comprised
      25 healthy volunteers in mean age 36.0 +/- 7.2 years. Following parameters were
      determined: plasma and blood viscosity, erythrocyte and platelets aggregation,
      erythrocyte deformability, hematocrit, beta-thromboglobulin plasma concentration,
      plasma fibrinogen concentration, lipids concentration, noradrenaline, adrenaline,
      serotonin, neuropeptide Y plasma concentrations. Plasma fibrinogen and beta
      thromboglobulin were increased in pheochromocytoma before surgery after
      pharmacological treatment and also after excision of the tumor. Whereas altered
      erythrocyte deformability before any treatment, only. Plasma neuropeptide Y
      concentration was higher in pheochromocytoma before surgery and after
      pharmacological treatment. There was no correlation between plasma
      catecholamines, plasma fibrinogen, beta-thromboglobulin, and erythrocyte
      deformability. Our results suggest that rheological abnormalities observed in
      patients with pheochromocytoma may contribute to vascular complications in this
      subjects. Sympathetic nervous system seems to influence indirectly observed
      rheological abnormalities.

PMID- 8755850
TI  - [Polymorphic variability of apolipoprotein B genes and insulin receptor in
      essential hypertension].
AB  - The association of the polymorphisms of two candidate genes with essential
      hypertension was studied in 74 hypertensive and 118 normotensive subjects. Two
      restrictions endonucleases were used: PstI for the insulin receptor gene and
      PvuII for the apolipoprotein B gene. PstI RFLP in the INSR gene locus consists of
      two polymorphic alleles P1 (1800bp) and P2 (1500bp). Frequencies of these alleles
      in general population are 0.15 and 0.85 respectively. The results showed
      statistically significant association between P1 allele and homozygotus genotype
      P1P1 for the INSR gene and essential hypertension. Clinical data of homozygotus
      P1P1 individuals revealed earlier clinical onset and more severe course of the
      disease. PvuII RFLP in the apoB gene locus consists of two polymorphic alleles
      Pul (7900bp) and Pu2(5500 bp). Frequencies of these alleles in general population
      are 0.93 and 0.07 respectively. In the apoB gene analysis Pu1 and Pu2 allele
      frequencies were similar in both studied groups. However the higher frequency of
      homozygotus genotype Pu1Pu2 was observed in hypertension.

PMID- 8755851
TI  - [Fructosamine in blood serum, binding and degradation of 125J-insulin by
      erythrocyte receptors in young persons with type I diabetes--effect of physical
      exercise].
AB  - The aim of investigation was the determination of the effect of regular physical
      exercise of intensity 35% VO2max on glycolysation of proteins, expressed by
      fructosamine concentration in blood serum and on insulin sensitivity of
      erythrocyte receptors in children with diabetes mellitus type I. The
      investigations were performed with 10 young persons with diabetes mellitus type
      I, during their sanatorium treatment. During 21 days the children effected every
      day a 20-minutes ergometric exercise of intensity equivalent approximately to 35%
      VO2max. Before the 3-weeks therapy and after its termination the examined
      children have performed an ergometric test exercise, with collection of blood
      samples. Obtained results allow to ascertain, that regular aerobic exercise
      contributed to the growth of physical efficiency expressed by the VO2max value,
      reduction in fructosamine level in blood serum, increase in insulin sensitivity
      of erythrocyte receptor and improved effort tolerance related to glycemia.

PMID- 8755852
TI  - [Comparison of captopril angioscintigraphy and the renin test in diagnosis of
      renovascular hypertension].
AB  - Captopril renin test (CRT) and captopril angioscintigraphic test (CAT) were
      simultaneously performed in 130 patients with arterial hypertension (72 women, 58
      men, average age 48 years) and suspension for renovascular hypertension (RVH) in
      initial renal angioscintigraphy. 16 positive CAT results and 26 positive CRT
      results according to Muller qualification as well as 31 positive results
      according to Frederickson qualification were obtained. In 32 patients the
      suspension of RVH was formed on the basis of clinical features of accelerated
      phase of hypertension. In 42 patients the renal arteriography was performed-this
      group includes all patients with positive results of at least one captopril test,
      among them 32 patients with clinical symptoms of accelerated hypertension. In 24
      cases the critical stenosis of renal artery was revealed. The diagnostic value of
      CRT-M, CRT-F and CAT was referred to critical stenosis of renal artery (> 75% of
      the lumen) as a criterium of RVH. The following values of sensitivity,
      specificity and discrimination capacity for CRT were established: for CRT-M 70%,
      50%, 21% respectively, for CRT-F 88%, 44%, 40% respectively. CAT demonstrated the
      highest specificity (100%) as well as discrimination capacity (75%) in spite of
      the relatively low sensitivity (67%). The absence of false positive results of
      CAT as well as considerable percentage of false positive CRT results stress the
      importance of isotopic test as basic method for the diagnosis of RVH. Simplicity
      of the test, its low price and availability as well as immediately obtained
      results allow to propose CAT as a routine ambulatory screening test for RVH.

PMID- 8755853
TI  - [Myoneuropathy in patients with chronic renal failure treated with hemodialysis
      (HD) and intermittent peritoneal dialysis (IPD). I. Evaluation of myoelectric
      activity of selected skeletal muscles in patients with chronic renal failure
      treated with hemodialysis and intermittent peritoneal dialysis].
AB  - The aim of the study was the analysis of the sequence of electrophysiological
      changes occurring in the skeletal muscles in patients with chronic renal failure
      treated with hemodialysis (HD) and intermittent peritoneal dialysis (IPD). In 30
      patients (10 treated with IPD-group I, 20 with HD-group II) the global
      electromyography (EMG) was determined in the muscles: pectoralis, obliqus and
      rectus abd., biceps brachii, thenar and hypothenar. The fatigue test was
      determined in the m. biceps brachii. The examinations were done twice during the
      12 months of observations. The analysis of the material showed that myoelectrical
      activity of the examined muscles was significantly lower compared to a control
      group and did not changed during the 12 months of observations. The results of
      the fatigue test showed that in uremic patients the fatiguability of m. biceps
      brachii was significantly greater and was deeper after 12 months of observations.
      The analysis of the maximal inspiratory and expiratory pressure showed that
      respiratory muscles in uremic patients were weak. The results of the measurements
      the hand grip pressure showed that hand muscles were weak also.

PMID- 8755854
TI  - [Myoneuropathy in patients with chronic renal failure treated with hemodialysis
      (HD) and intermittent peritoneal dialysis (IPD). II. Sensory and motor nerve
      conduction velocity in patients with chronic renal failure treated with
      intermittent peritoneal dialysis and hemodialysis].
AB  - The aim of the study was the analysis of the sequence of electrophysiological
      changes occurring in the peripheral nerves in patients with chronic renal failure
      treated with hemodialysis and intermittent peritoneal dialysis. In 33 patients
      (21 treated with hemodialysis and in 12 treated with intermittent peritoneal
      dialysis) impulse conduction was determined in the motor and sensory fibers
      nerves. The examinations were done twice during 12 months of observations. The
      analysis of the material showed that sensory nerve conduction velocity was normal
      in all patients and did not changed during the study. Motor nerve conduction
      velocity was however significantly slower in all patients and did not changed
      during the study. The amplitude of sensory response was lower in all patients,
      the values of subjective and objective sensory response were higher compared to a
      control group. In all patient the quantitative EMG of m. abd. pollicis brevis was
      done. A signs of neurogenic atrophy were found in all patients. Only in one
      patients we observed signs of primary myopathy. There were no differences in the
      electrophysiological parameters in the patients treated with hemodialysis and
      with intermittent peritoneal dialysis.

PMID- 8755855
TI  - [A case of primary hepatocellular carcinoma with tumor thrombus in the right
      atrium and massive pulmonary embolism].
AB  - We present a case report of primary hepatocellular carcinoma with tumor thrombus
      extending into the right atrium complicated by pulmonary embolism. A 49-year-old
      man was admitted to our hospital for searching a cause of thrombus in the right
      atrium. The patient complained of shortness of breath and oedema of the lower
      extremities. He had a history of hepatitis B. Abdominal sonography and computed
      tomography revealed a tumor of the liver. A needle biopsy confirmed the diagnosis
      of hepatocellular carcinoma. Magnetic resonance showed a tumor thrombus also in
      the inferior vena cava. The diagnosis of pulmonary embolism was confirmed by
      pulmonary perfusion scintigraphy. This case stresses that clinicians should
      include hepatocellular carcinoma among the possible causes of intracardiac
      thrombus and pulmonary embolism.

PMID- 8755856
TI  - [Perforation in the gastrointestinal tract as a complication of acute leukemia].
AB  - Two cases of gastrointestinal perforation in patients with acute leukemia are
      reported. They were thrombocytopenic, but successfully surgically treated.

PMID- 8755857
TI  - [Cough as an adverse effect during angiotensin-converting enzyme inhibitor
      therapy].

PMID- 8755858
TI  - [Pathophysiologic and clinical aspects of usefulness regarding angiotensin
      converting enzyme inhibitors in diabetes].

PMID- 8755859
TI  - [Interleukin 6 (IL-6)--clinical significance].

PMID- 8755860
TI  - Probing the structure, function, and interactions of the Escherichia coli H-NS
      and StpA proteins by using dominant negative derivatives.
AB  - Twelve different dominant negative mutants of the Escherichia coli nucleoid
      associated protein, H-NS, have been selected and characterized in vivo. The
      mutants are all severely defective in promoter repression activity in a strain
      lacking H-NS, and they all disrupt the repression normally exerted by H-NS at two
      of its target promoters. From the locations of the alterations in these mutants,
      which result in both large truncations and amino acid substitutions, we propose
      that H-NAS contains at least two distinct domains. The in vitro protein-protein
      cross-linking data presented in this report indicate that the proposed N-terminal
      domain of H-NS has a role in H-NS multimerization. StpA is a protein with known
      structural and functional homologies to H-NS. We have analyzed the extent of
      these homologies by constructing and studying StpA mutants predicted to be
      dominant negative. Our data indicate that the substitutions and deletions found
      in dominant negative H-NS have similar effects in the context of StpA. We
      conclude that the domain organizations and functions in StpA and H-NS are closely
      related. Furthermore, dominant negative H-NS can disrupt the activity of native
      StpA, and reciprocally, dominant negative StpA can disrupt the activity of native
      H-NS. We demonstrate that the N-terminal domain of H-NS can be chemically cross
      linked to both full-length H-NS and StpA. We account for these observations by
      proposing that H-NS and StpA have the ability to form hybrid species.

PMID- 8755861
TI  - Global analysis of proteins synthesized during phosphorus restriction in
      Escherichia coli.
AB  - The pattern of proteins synthesized in Escherichia coli during steady-state
      growth in media with ample inorganic phosphate (Pi), upon limitation for Pi
      (without an alternative phosphorous compound), and during steady-state growth in
      media containing phosphonate (PHN) as the sole P source was examined by two
      dimensional gel electrophoresis. Of 816 proteins monitored in these experiments,
      all those with differential synthesis rates greater than 2.0 or less than 0.5
      upon phosphate limitation (P limitation) or during growth on PHN compared with
      their rates in the cultures with Pi were classified as belonging to the PL or PHN
      stimulon, respectively. The PL stimulon included 413 proteins, 208 showing
      induced synthesis and 205 showing repressed synthesis. The PHN stimulon was
      smaller: it included 257 proteins; 227 showed induced synthesis and 30 showed
      repressed synthesis. The overlap of the two stimulons included 137 proteins: most
      (118) were ones showing induced synthesis. The promoter regions of genes for
      several of the proteins with induced or repressed synthesis contained sequences
      which resembled the consensus sequence for PhoB binding. The aggregate mass of
      proteins responding to P limitation or growth on PHN was 30 to 40% of the cells'
      total mass. By comparing the proteins responding to P limitation with those
      responding to growth on PHN, one can speculate which proteins are likely involved
      in adapting cells to new P sources or in preparing cells to survive stationary
      phase.

PMID- 8755862
TI  - Dynamics of denitrification activity of Paracoccus denitrificans in continuous
      culture during aerobic-anaerobic changes.
AB  - Induction and repression of denitrification activity were studied in a continuous
      culture of Paracoccus denitrificans during changes from aerobic to anaerobic
      growth conditions and vice versa. The denitrification activity of the cells was
      monitored by measuring the formation of denitrification products (nitrite, nitric
      oxide, nitrous oxide, and dinitrogen), individual mRNA levels for the nitrate,
      nitrite, and nitrous oxide reductases, and the concentration of the nitrite
      reductase enzyme with polyclonal antibodies against the cd1-type nitrite
      reductase. On a change from aerobic to anaerobic respiration, the culture entered
      an unstable transition phase during which the denitrification pathway became
      induced. The onset of this phase was formed by a 15- to 45-fold increase of the
      mRNA levels for the individual denitrification enzymes. All mRNAs accumulated
      during a short period, after which their overall concentration declined to reach
      a stable value slightly higher than that observed under aerobic steady-state
      conditions. Interestingly, the first mRNAs to be formed were those for nitrate
      and nitrous oxide reductase. The nitrite reductase mRNA appeared significantly
      later, suggesting different modes of regulation for the three genes. Unlike the
      mRNA levels, the level of the nitrite reductase protein increased slowly during
      the anaerobic period, reaching a stable value about 30 h after the switch. All
      denitrification intermediates could be observed transiently, but when the new
      anaerobic steady state was reached, dinitrogen was the main product. When the
      anaerobic cultures were switched back to aerobic respiration, denitrification of
      the cells stopped at once, although sufficient nitrite reductase was still
      present. We could observe that the mRNA levels for the individual denitrification
      enzymes decreased slightly to their aerobic, uninduced levels. The nitrite
      reductase protein was not actively degraded during the aerobic period.

PMID- 8755863
TI  - Bacillus subtilis spore coat assembly requires cotH gene expression.
AB  - Endospores of Bacillus subtilis are encased in a protein shell, known as the
      spore coat, composed of a lamella-like inner layer and an electron-dense outer
      layer. We report the identification and characterization of a gene, herein called
      cotH, located at 300 degrees on the B. subtilis genetic map between two divergent
      cot genes, cotB and cotG. The cotH open reading frame extended for 1,086 bp and
      corresponded to a polypeptide of 42.8 kDa. Spores of a cotH null mutant were
      normally heat, lysozyme, and chloroform resistant but were impaired in
      germination. The mutant spores were also pleiotropically deficient in several
      coat proteins, including the products of the previously cloned cotB, -C, and -G
      genes. On the basis of the analysis of a cotE cotH double mutant, we infer that
      CotH is probably localized in the inner coat and is involved in the assembly of
      several proteins in the outer layer of the coat.

PMID- 8755864
TI  - Isolation of a gene involved in 1,3-beta-glucan synthesis in Aspergillus nidulans
      and purification of the corresponding protein.
AB  - Saccharomyces cerevisiae has two highly homologous genes, FKS1 and FKS2, which
      encode interchangeable putative catalytic subunits of 1,3-beta-glucan synthase
      (GS), an enzyme that synthesizes an essential polymer of the fungal cell wall. To
      determine if GS in Aspergillus species is similar, an FKS homolog, fksA, was
      cloned from Aspergillus nidulans by cross-hybridization, and the corresponding
      protein was purified. Sequence analysis revealed a 5,716-nucleotide coding region
      interrupted by two 56-bp introns. The fksA gene encodes a predicted peptide of
      229 kDa, FksAp, that shows a remarkable degree of conservation in size, charge,
      amino acid identity, and predicted membrane topology with the S. cerevisiae FKS
      proteins (Fksps). FksAp exhibits 64 and 65% identity to Fks1p and Fks2p,
      respectively, and 79% similarity. Hydropathy analysis of FksAp suggests an
      integral membrane protein with 16 transmembrane helices that coincide with the
      transmembrane helices of the Saccharomyces Fksps. The sizes of the
      nontransmembrane domains are strikingly similar to those of Fks1p. The region of
      FksAp most homologous to the Saccharomyces FKS polypeptides is a large
      hydrophilic domain of 578 amino acids that is predicted to be cytoplasmic. This
      domain is 86% identical to the corresponding region of Fks1p and is a good
      candidate for the location of the catalytic site. Antibodies raised against a
      peptide derived from the FksAp sequence recognize a protein of approximately 200
      kDa in crude membranes and detergent-solubilized active extracts. This protein is
      enriched approximately 300-fold in GS purified by product entrapment. Purified
      anti-FksAp immunoglobulin G immunodepletes nearly all of the GS activity in crude
      or purified extracts when Staphylococcus aureus cells are used to precipitate the
      antibodies, although it does not inhibit enzymatic activity when added to
      extracts. The purified GS is inhibited by echinocandins with a sensitivity equal
      to that displayed by whole cells. Thus, the product of fksA is important for the
      activity of highly purified preparations of GS, either as the catalytic subunit
      itself or as an associated copurifying subunit that mediates susceptibility of
      enzymatic activity to echinocandin inhibition.

PMID- 8755865
TI  - Genes encoding the pKM101 conjugal mating pore are negatively regulated by the
      plasmid-encoded KorA and KorB proteins.
AB  - The IncN plasmid pKM101 contains a group of 11 genes thought to be required for
      the synthesis of its conjugal pilus and mating pore. Within this region are two
      genes, kilA and kilB, either of which is conditionally lethal to the cell. kilA
      was previously shown to be allelic with traL, and we now show that kilB is
      allelic with traE. In the same region, genetic studies previously defined two
      loci, korA and korB (kor for kill override), which together prevent lethality
      mediated by kilA and kilB. We now identify the genes that encode KorA and KorB
      functions. To determine whether KorA and KorB proteins influence tra gene
      transcription, we constructed beta-galactosidase fusions to three promoters in
      this region and measured their expression in the presence of KorA, KorB, and both
      proteins. KorA and KorB together repressed transcription of all three promoters,
      while neither protein alone affected transcription. We identified all three
      transcriptional start sites by primer extension analysis. Two putative binding
      sites for these proteins, designated kor boxes, contain 26 identical nucleotides
      in a 29-nucleotide region. The electrophoretic mobilities (of DNA fragments
      containing kor boxes were retarded by cell extracts containing both KorA and KorB
      but were not retarded by extracts containing just KorA or just KorB. DNase I
      footprinting analysis of one of these promoters demonstrates that KorA and/or
      KorB binds to a region containing a kor box.

PMID- 8755866
TI  - The genetic requirements for UmuDC-mediated cold sensitivity are distinct from
      those for SOS mutagenesis.
AB  - The umuDC operon of Escherichia coli, a member of the SOS regulon, is required
      for SOS mutagenesis. Following the posttranslational processing of UmuD to UmuD'
      by RecA-mediated cleavage, UmuD' acts in concert with UmuC, RecA, and DNA
      polymerase III to facilitate the process of translesion synthesis, which results
      in the introduction of mutations. Constitutive expression of the umuDC operon
      causes an inhibition of growth at 30 degrees C (cold sensitivity). The umuDC
      dependent physiological phenomenon manifested as cold-sensitive growth is shown
      to differ from SOS mutagenesis in two respects. Intact UmuD, the form inactive in
      SOS mutagenesis, confers a significantly higher degree of cold sensitivity in
      combination with UmUC than does UmuD'. In addition, umuDC-mediated cold
      sensitivity, unlike SOS mutagenesis, does not require recA function. Since the
      RecA protein mediates the autodigestion of UnmD to UmuD', this finding supports
      the conclusion that intact UmuD is capable of conferring cold sensitivity in the
      presence of UmuC. The degree of inhibition of growth at 30 degrees C correlates
      with the levels of UmuD and UmuC, which are the only two SOS-regulated proteins
      required to observe cold sensitivity. Analysis of the cellular morphology of
      strains that exhibit cold sensitivity for growth led to the finding that
      constitutive expression of the umuDC operon causes a novel form of sulA- and sfiC
      independent filamentation at 30 degrees C. This filamentation is observed in a
      strain constitutively expressing the single, chromosomal copy of umuDC and can be
      suppressed by overexpression of the ftsQAZ operon.

PMID- 8755867
TI  - Mutations in the Corynebacterium glutamicum proline biosynthetic pathway: a
      natural bypass of th proA step.
AB  - Two chromosomal loci containing the Corynebacterium glutamicum ATCC 17965 proB
      and proC genes were isolated by complementation of Escherichia coli proB and proC
      auxotrophic mutants. Together with a proA gene described earlier, these new genes
      describe the major C. glutamicum proline biosynthetic pathway. The proB and proA
      genes, closely linked in most bacteria, are in C. glutamicum separated by a 304
      amino-acid open reading frame (unk) whose predicted sequence resembles that of
      the 2-hydroxy acid dehydrogenases. C. glutamicum mutants that carry null alleles
      of proB, proA, and proC were constructed or isolated from mutagenized cultures.
      Single proC mutants are auxotrophic for proline and secrete delta1-pyrroline-5
      carboxylate, which are the expected phenotypes of bacterial proC mutants.
      However, the phenotypes or proB and proA mutants are unexpected. A proB mutant
      has a pleiotropic phenotype, being both proline auxotrophic and affected in cell
      morphology. Null proA alleles still grow slowly under proline starvation, which
      suggests that a proA-independent bypass of this metabolic step exists in C.
      glutamicum. Since proA mutants are complemented by a plasmid that contains the
      wild-type asd gene of C. glutamicum, the asd gene may play a role in this bypass.

PMID- 8755868
TI  - A novel autonomously replicating sequence (ARS) for multiple integration in the
      yeast Hansenula polymorpha DL-1.
AB  - Several autonomously replicating sequences of Hansenula polymorpha DL-1 (HARSs)
      with the characteristics of tandem integration were cloned by an enrichment
      procedure and analyzed for their functional elements to elucidate the mechanism
      of multiple integration in tandem repeats. All plasmids harboring newly cloned
      HARSs showed a high frequency of transformation and were maintained episomally
      before stabilization. After stabilization, the transforming DNA was stably
      integrated into the chromosome. HARS36 was selected for its high efficiency of
      transformation and tendency for integration. Several tandemly repeated copies of
      the transforming plasmid containing HARS36 (pCE36) integrated into the vicinity
      of the chromosomal end. Bal 31 digestion of the total DNA from the integrants
      followed by Southern blotting generated progressive shortening of the
      hybridization signal, indicating the telomeric localization of the transforming
      plasmids on the chromosome. The minimum region of HARS36 required for its HARS
      activity was analyzed by deletion analyses. Three important regions, A, B, and C,
      for episomal replication and integration were detected. Analysis of the DNA
      sequences of regions A and B required for the episomal replication revealed that
      region A contained several AT-rich sequences that showed sequence homology with
      the ARS core consensus sequence of Saccharomyces cerevisiae. Region B contained
      two directly repeated sequences which were predicted to form a bent DNA
      structure. Deletion of the AT-rich core in region A resulted in a complete loss
      of ARS activity, and deletion of the repeated sequences in region B greatly
      reduced the stability of the transforming plasmid and resulted in retarded cell
      growth. Region C was required for the facilitated chromosomal integration of
      transforming plasmids.

PMID- 8755869
TI  - The integrons In0, In2, and In5 are defective transposon derivatives.
AB  - The class 1 integrons In0, In2, and In5, found in different locations in pVS1,
      Tn21, and pSCH884, have closely related structures. All three integrons contain
      an insertion sequence, IS1326, that is a new member of the IS21 family. IS1326
      has caused deletions of adjacent 3'-conserved segment and transposition module
      sequences, and all three integrons retain a complete copy of only one of four
      genes required for transposition of related transposons and are thus defective
      transposon derivatives. In2 contains an additional insertion sequence, IS1353,
      located within IS1326. IS1353 is a member of the IS3 family and appears to have
      been acquired after the integron was inserted into an ancestral mercury
      resistance transposon to create the ancestor of Tn21 and several other
      transposons that are close relatives of Tn21.

PMID- 8755870
TI  - Starvation-induced expression of retron-Ec107 and the role of ppGpp in multicopy
      single-stranded DNA production.
AB  - Multicopy single-stranded DNA is found as a small single-stranded RNA-DNA complex
      in certain wild-type strains of Escherichia coli as well as in other gram
      negative bacteria. Using the promoter region of the previously characterized
      retron-Ec107 from E. coli ECOR70, I constructed a chromosomally located lacZ
      operon fusion. Examination of expression from the PEc107 promoter showed that
      activity increased sharply when cells entered stationary phase in rich medium or
      when they were starved for phosphate. The nucleotide guanosine-3',5'
      bispyrophosphate was found to be a positive regulator of retron-Ec107 expression.
      Its presence is required for starvation-induced transcription of retron-Ec107 and
      multicopy single-stranded DNA production. It was also found that expression from
      the retron promoter is independent of the sigma factor sigmaS.

PMID- 8755871
TI  - A new gene locus of Bordetella pertussis defines a novel family of prokaryotic
      transcriptional accessory proteins.
AB  - Recently, a novel type of regulatory mutation causing differential effects on the
      expression of virulence genes due to a slight overexpression of the RNA
      polymerase alpha subunit (RpoA) was found in Bordetella pertussis (N. H.
      Carbonetti, T. M. Fuchs, A. A. Patamawenu, T. J. Irish, H. Deppisch, and R.
      Gross, J. Bacteriol. 176:7267-7273, 1994). To gather information on the molecular
      events behind this phenomenon, we isolated suppressor mutants of the RpoA
      overexpressing strains after random mutagenesis. Genetic characterization of
      these suppressor strains revealed the existence of at least three distinct groups
      of dominant alleles. Mutations occurred either in the rpoA locus itself, in the
      bvg locus, or in unknown gene loci. One mutant of the latter group was further
      characterized. By the introduction of a cosmid library containing genomic B.
      pertussis DNA into this suppressor strain, we isolated a cosmid which suppressed
      the phenotype of the suppressor strain, thus restoring the negative effect on
      transcription of the ptx and cya toxin genes. Mutagenesis of the cosmid with Tn5
      led to the identification of the gene locus responsible for this phenomenon. Its
      DNA sequence revealed the presence of an open reading frame (ORF) consisting of
      2,373 bp coding for a hypothetical 86-kDa protein with extensive sequence
      similarities to ORFs with not yet identified functions of Escherichia coli,
      Haemophilus influenzae, and Neisseria meningitidis. The new gene, termed tex, for
      toxin expression, seems to be an essential factor for B. pertussis, as it cannot
      be deleted from the bacterial chromosome. All members of this new protein family
      show significant sequence similarities with the mannitol repressor protein MtlR
      and with the presumptive RNA-binding domains of the Pnp and ribosomal S1 proteins
      of E. coli in their N- and C-terminal parts, respectively. These sequence
      similarities and the fact that the tex gene was isolated by virtue of its effects
      on gene expression in B. pertussis indicate that the members of this new protein
      family may play an important role in the transcription machinery of prokaryotic
      organisms.

PMID- 8755872
TI  - Involvement of the GroE chaperonins in the nickel-dependent anaerobic
      biosynthesis of NiFe-hydrogenases of Escherichia coli.
AB  - We analyzed the involvement of chaperonins GroES and GroEL in the biosynthesis of
      the three hydrogenase isoenzymes, HYD1, HYD2, and HYD3, of Escherichia coli.
      These hydrogenases are NiFe-containing, membrane-bound enzymes composed of small
      and large subunits, each of which is proteolytically processed during
      biosynthesis. Total hydrogenase activity was found to be reduced by up to 60% in
      groES and groEL thermosensitive mutant strains. This effect was specific because
      it was not seen for another oligomeric, membrane-bound metalloenzyme, i.e.,
      nitrate reductase. Analyses of the single hydrogenase isoenzymes revealed that a
      temperature shift during the growth of groE mutants led to an absence of HYD1
      activity and to an accumulation of the precursor of the large subunit of HYD3,
      whereas only marginal effects on the processing of HYD2 and its activity were
      observed under these conditions. A decrease in total hydrogenase activity,
      together with accumulation of the precursors of the large subunits of HYD2 and
      HYD3, was also found to occur in a nickel uptake mutant (nik). The phenotype of
      this nik mutant was suppressed by supplementation of the growth medium with
      nickel ions. On the contrary, Ni2+ no longer restored hydrogenase activity and
      processing of the large subunit of HYD3 when the nik and groE mutations were
      combined in one strain. This finding suggests the involvement of these
      chaperonins in the biosynthesis of a functional HYD3 isoenzyme via the
      incorporation of nickel. In agreement with these in vivo results, we demonstrated
      a specific binding of GroEL to the precursor of the large subunit of HYD3 in
      vitro. Collectively, our results are consistent with chaperonin-dependent
      incorporation of nickel into the precursor of the large subunit of HYD3 as a
      prerequisite of its proteolytic processing and the acquisition of enzymatic
      activity.

PMID- 8755873
TI  - An alternative pathway of recombination of chromosomal fragments precedes recA
      dependent recombination in the radioresistant bacterium Deinococcus radiodurans.
AB  - Deinococcus radiodurans R1 and other members of this genus are able to repair and
      survive extreme DNA damage induced by ionizing radiation and many other DNA
      damaging agents. The ability of R1 to repair completely > 100 double-strand
      breaks in its chromosome without lethality or mutagenesis is recA dependent.
      However, during the first 1.5 h after irradiation, recA+ and recA cells show
      similar increases in the average size of chromosomal fragments. In recA+ cells,
      DNA continues to enlarge to wild-type size within 29 h. However, in recA cells,
      no DNA repair is observed following the first 1.5 h postirradiation. This recA
      independent effect was studied further, using two slightly different Escherichia
      coli plasmids forming adjacent duplication insertions in the chromosome,
      providing repetitive sequences suitable for circularization by non-recA-dependent
      pathways following irradiation. After exposure to 1.75 Mrad (17,500 Gy), circular
      derivatives of the integration units were detected in both recA+ and recA cells.
      These DNA circles were formed in the first 1.5 h postirradiation, several hours
      before the onset of detectable recA-dependent homologous recombination. By
      comparison, D. radiodurans strains containing the same E. coli plasmids as
      nonrepetitive direct insertions did not form circular derivatives of the
      integration units before or after irradiation in recA+ or recA cells. The
      circular derivatives of the tandemly integrated plasmids were formed before the
      onset of recA-dependent repair and have structures consistent with the hypothesis
      that DNA repair occurring immediately postirradiation is by a recA-independent
      single-strand annealing reaction and may be a preparatory step for further DNA
      repair in wild-type D. radiodurans.

PMID- 8755874
TI  - Characterization of the locus responsible for the bacteriocin production in
      Lactobacillus plantarum C11.
AB  - Lactobacillus plantarum C11 secretes a small cationic peptide, plantaricin A,
      that serves as induction signal for bacteriocin production as well as
      transcription of plnABCD. The plnABCD operon encodes the plantaricin A precursor
      (PlnA) itself and determinants (PlnBCD) for a signal transducing pathway. By
      Northern (RNA) and sequencing analyses, four new plantaricin A-induced operons
      were identified. All were highly activated in concert with plnABCD upon
      bacteriocin induction. Two of these operons (termed plnEFI and plnJKLR) each
      encompass a gene pair (plnEF and plnJK, respectively) encoding two small cationic
      bacteriocin-like peptides with double-glycine-type leaders. The open reading
      frames (ORFs) encoding the bacteriocin-like peptides are followed by ORFs (plnI
      and -L, respectively) encoding cationic hydrophobic proteins resembling
      bacteriocin immunity proteins. On the third operon (termed plnMNOP), a similar
      bacteriocin-like ORF (plnN) and a putative immunity ORF (either plnM or -P) were
      identified as well. These findings suggest that two bacteriocins of two-peptide
      type (mature PlnEF and PlnJK) and a bacteriocin of one-peptide type (mature PlnN)
      could be responsible for the observed bacteriocin activity. The last operon
      (termed plnGHSTUV) contains two ORFs (plnGH) apparently encoding an ABC
      transporter and its accessory protein, respectively, known to be involved in
      processing and export of peptides with precursor double-glycine-type leaders.
      Promoter structure was established. A conserved regulatory-like box encompassing
      two direct repeats was identified in the promoter regions of all five plantaricin
      A-induced operons. These repeats may serve as regulatory elements for gene
      expression.

PMID- 8755875
TI  - Stationary phase-associated protein expression in Mycobacterium tuberculosis:
      function of the mycobacterial alpha-crystallin homolog.
AB  - The majority of active tuberculosis cases arise as a result of reactivation of
      latent organisms which are quiescent within the host. The ability of mycobacteria
      to survive extended periods without active replication is a complex process whose
      details await elucidation. We used two-dimensional gel electrophoresis to examine
      both steady-state protein composition and time-dependent protein synthetic
      profiles in aging cultures of virulent Mycobacterium tuberculosis. At least seven
      proteins were maximally synthesized 1 to 2 weeks following the end of log-phase
      growth. One of these proteins accumulated to become a predominant stationary
      phase protein. N-terminal amino acid sequencing and immunoreactivity identified
      this protein as the 16-kDa alpha-crystallin-like small heat shock protein. The
      gene for this protein was shown to be limited to the slowly growing M.
      tuberculosis complex of organisms as assessed by Southern blotting.
      Overexpression of this protein in wild-type M. tuberculosis resulted in a slower
      decline in viability following the end of log-phase growth. Accumulation of this
      protein was observed in log-phase cultures following a shift to oxygen-limiting
      conditions but not by other external stimuli. The protein was purified to
      homogeneity from overexpressing M. smegmatis in two steps and shown to have a
      significant ability to suppress the thermal denaturation of alcohol
      dehydrogenase. Collectively, these results suggest that the mycobacterial alpha
      crystallin protein may play a role in enhancing long-term protein stability and
      therefore long-term survival of M. tuberculosis.

PMID- 8755876
TI  - Isolation and characterization of the VnfEN genes of the cyanobacterium Anabaena
      variabilis.
AB  - The filamentous cyanobacterium Anabaena variabilis fixes nitrogen in the presence
      of vanadium (V) and in the absence of molybdenum (Mo), using a V-dependent
      nitrogenase (V-nitrogenase) encoded by the vnfDGK genes. Downstream from these
      genes are two genes that are similar to the vnfEN genes of Azotobacter
      vinelandii. Like the vnfDGK genes, the vnfEN genes were transcribed in the
      absence of Mo, whether or not V was present. A mutant with an insertion in the
      vnfN gene lacked V-nitrogenase activity; thus, the vnfEN genes were essential for
      the V-nitrogenase system in A. variabilis. Growth and acetylene reduction assays
      with wild-type and mutant strains suggested that the V-nitrogenase reduced
      dinitrogen better than acetylene. The similarity of the vnfEN genes of A.
      variabilis and A. vinelandii was not strong. The vnfEN genes of A. variabilis
      showed greater similarity to the vnfDK genes just upstream than to the A.
      vinelandii vnfEN genes. Sequence comparisons provide support for the idea that if
      the vnf genes were transferred laterally among bacterial strains, the vnf cluster
      was not transferred intact. It appears likely that the structural genes were
      transferred before a duplication event led to the evolution of the vnfEN genes
      independently in the two strains. The divergence of the vnfEN genes from the
      vnfDK genes suggests that this duplication, and hence the transfer of vnf genes,
      was an ancient event.

PMID- 8755877
TI  - A compartmentalized regulator of developmental gene expression in Bacillus
      subtilis.
AB  - We have identified a new Bacillus subtilis gene, spoVT, whose gene product is
      homologous to the transcriptional regulator AbrB and serves as a regulator of E
      sigmaG-controlled gene expression. SpoVT acts both positively and negatively in
      controlling sigmaG-dependent gene expression, providing an additional level of
      refinement to forespore gene regulation and feedback control of spoIIIG
      expression.

PMID- 8755878
TI  - Biochemical characterization of NfsA, the Escherichia coli major nitroreductase
      exhibiting a high amino acid sequence homology to Frp, a Vibrio harveyi flavin
      oxidoreductase.
AB  - We identified the nfsA gene, encoding the major oxygen-insensitive nitroreductase
      in Escherichia coli, and determined its position on the E. coli map to be 19 min.
      We also purified its gene product, NfsA, to homogeneity. It was suggested that
      NfsA is a nonglobular protein with a molecular weight of 26,799 and is associated
      tightly with a flavin mononucleotide. Its amino acid sequence is highly similar
      to that of Frp, a flavin oxidoreductase from Vibrio harveyi (B. Lei, M. Liu, S.
      Huang, and S.-C. Tu, J. Bacteriol. 176:3552-3558, 1994), an observation
      supporting the notion that E. coli nitroreductase and luminescent-bacterium
      flavin reductase families are intimately related in evolution. Although no
      appreciable sequence similarity was detected between two E. coli nitroreductases,
      NfsA and NfsB, NfsA exhibited a low level of the flavin reductase activity and a
      broad electron acceptor specificity similar to those of NfsB. NfsA reduced
      nitrofurazone by a ping-pong Bi-Bi mechanism possibly to generate a two-electron
      transfer product.

PMID- 8755879
TI  - O2 as the regulatory signal for FNR-dependent gene regulation in Escherichia
      coli.
AB  - With an oxystat, changes in the pattern of expression of FNR-dependent genes from
      Escherichia coli were studied as a function of the O2 tension (pO2) in the
      medium. Expression of all four tested genes was decreased by increasing O2.
      However, the pO2 values that gave rise to half-maximal repression (pO(0.5)) were
      dependent on the particular promoter and varied between 1 and 5 millibars (1 bar
      = 10(5) Pa). The pO(0.5) value for the ArcA-regulated succinate dehydrogenase
      genes was in the same range (pO(0.5) = 4.6 millibars). At these pO2 values, the
      cytoplasm can be calculated to be well supplied with O2 by diffusion. Therefore,
      intracellular O2 could provide the signal to FNR, suggesting that there is no
      need for a signal transfer chain. Genetic inactivation of the enzymes and
      coenzymes of aerobic respiration had no or limited effects on the pO(0.5) of FNR
      regulated genes. Thus, neither the components of aerobic respiration nor their
      redox state are the primary sites for O2 sensing, supporting the significance of
      intracellular O2. Non-redox-active, structural O2 analogs like CO, CN-, and N3-,
      could not mimic the effect of O2 on FNR-regulated genes under anaerobic
      conditions and did not decrease the inhibitory effect of O2 under aerobic
      conditions.

PMID- 8755880
TI  - The Alcaligenes eutrophus membrane-bound hydrogenase gene locus encodes functions
      involved in maturation and electron transport coupling.
AB  - Alcaligenes eutrophus H16 produces two [NiFe] hydrogenases which catalyze the
      oxidation of hydrogen and enable the organism to utilize H2 as the sole energy
      source. The genes (hoxK and hoxG) for the heterodimeric, membrane-bound
      hydrogenase (MBH) are located adjacent to a series of eight accessory genes
      (hoxZ, hoxM, hoxL, hoxO, hoxQ, hoxR, hoxT, and hoxV). In the present study, we
      generated a set of isogenic mutants with in-frame deletions in the two structural
      genes and in each of the eight accessory genes. The resulting mutants can be
      grouped into two classes on the basis of the H2-oxidizing activity of the MBH.
      Class I mutants (hoxKdelta, hoxGdelta, hoxMdelta, hoxOdelta, and hoxQdelta) were
      totally devoid of MBH-mediated, H2-oxidizing activity. The hoxM deletion strain
      was the only mutant in our collection which was completely blocked in carboxy
      terminal processing of large subunit HoxG, indicating that hoxM encodes a
      specific protease. Class II mutants (hoxZdelta, hoxLdelta, hoxRdelta, hoxTdelta,
      and hoxVdelta) contained residual amounts of MBH activity in the membrane
      fraction of the extracts. Immunochemical analysis and 63Ni incorporation
      experiments revealed that the mutations affect various steps in MBH maturation. A
      lesion in hoxZ led to the production of a soluble MBH which was highly active
      with redox dye.

PMID- 8755881
TI  - Temperature-dependent growth kinetics of Escherichia coli ML 30 in glucose
      limited continuous culture.
AB  - Detailed comparison of growth kinetics at temperatures below and above the
      optimal temperature was carried out with Escherichia coli ML 30 (DSM 1329) in
      continuous culture. The culture was grown with glucose as the sole limiting
      source of carbon and energy (100 mg liter(-1) in feed medium), and the resulting
      steady-state concentrations of glucose were measured as a function of the
      dilution rate at 17.4, 28.4, 37, and 40 degrees C. The experimental data could
      not be described by the conventional Monod equation over the entire temperature
      range, but an extended form of the Monod model [mu = mu(max) x (s - s(min))/(Ks +
      s - s(min))], which predicts a finite substrate concentration at 0 growth rate
      (s(min)), provided a good fit. The two parameters mu(max) and s(min) were
      temperature dependent, whereas, surprisingly, fitting the model to the
      experimental data yielded virtually identical Ks values (approximately 33 microg
      liter(-1)) at all temperatures. A model that describes steady-state glucose
      concentrations as a function of temperature at constant growth rates is
      presented. In similar experiments with mixtures of glucose and galactose (1:1
      mixture), the two sugars were utilized simultaneously at all temperatures
      examined, and their steady-state concentrations were reduced compared with to
      growth with either glucose or galactose alone. The results of laboratory-scale
      kinetic experiments are discussed with respect to the concentrations observed in
      natural environments.

PMID- 8755882
TI  - A phosphate transport system is required for symbiotic nitrogen fixation by
      Rhizobium meliloti.
AB  - The bacterium Rhizobium meliloti forms N2-fixing root nodules on alfalfa plants.
      The ndvF locus, located on the 1,700-kb pEXO megaplasmid of R. meliloti, is
      required for nodule invasion and N2 fixation. Here we report that ndvF contains
      four genes, phoCDET, which encode an ABC-type transport system for the uptake of
      Pi into the bacteria. The PhoC and PhoD proteins are homologous to the
      Escherichia coli phosphonate transport proteins PhnC and PhnD. The PhoT and PhoE
      proteins are homologous to each other and to the E. coli phosphonate transport
      protein PhnE. We show that the R. meliloti phoD and phoE genes are induced in
      response to phosphate starvation and that the phoC promoter contains two elements
      which are similar in sequence to the PHO boxes present in E. coli phosphate
      regulated promoters. The R. meliloti ndvF mutants grow poorly at a phosphate
      concentration of 2 mM, and we hypothesize that their symbiotic phenotype results
      from their failure to grow during the nodule infection process. Presumably, the
      PhoCDET transport system is employed by the bacteria in the soil environment,
      where the concentration of available phosphate is normally 0.1 to 1 microM.

PMID- 8755883
TI  - Identification and characterization of phoN-Sf, a gene on the large plasmid of
      Shigella flexneri 2a encoding a nonspecific phosphatase.
AB  - A gene encoding a nonspecific phosphatase, named PhoN-Sf, was identified on the
      large virulence plasmid (pMYSH6000) of Shigella flexneri 2a YSH6000. The
      phosphatase activity in YSH6000 was observed under high-phosphate conditions.
      However, it was found that low-phosphate conditions induced a slightly higher
      level of activity. The nucleotide sequence of the phoN-Sf region cloned from
      pMYSH6000 possessing the phoN-Sf gene encoded 249 amino acids with a typical
      signal sequence at the N terminus. The deduced amino acid sequence of the PhoN-Sf
      protein revealed significant homology to sequences of nonspecific acid
      phosphatases of other bacteria, such as Providencia stuartii (PhoN, 83.2%),
      Morganella morganii (PhoC, 80.6%), Salmonella typhimurium (PhoN, 47.8%), and
      Zymomonas mobilis (PhoC, 34.8%). The PhoN-Sf protein was purified, and its
      biochemical properties were characterized. The apparent molecular mass of the
      protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was
      calculated to be 27 kDa. The 20 amino acids at the N terminus corresponded to the
      20 amino acid residues following the putative signal sequence of PhoN-Sf protein
      deduced from the nucleotide sequence. The PhoN-Sf activity had a pH optimum of
      6.6, and the optimum temperature was 37 degrees C. The enzymatic activity was
      inhibited by diisopropyl fluorophosphate, N-bromosuccinimide, or dithiothreitol
      but not by EDTA. The subcellular localization of the PhoN-Sf protein in YSH6000
      revealed that the protein was found predominantly in the periplasm. Examination
      of Shigella and enteroinvasive Escherichia coli strains for PhoN-Sf production by
      immunoblotting with the PhoN-specific antibody and for the presence of phoN-Sf
      DNA by using a phoN-Sf probe indicated that approximately one-half of the strains
      possessed the phoN-Sf gene on the large plasmid and expressed the PhoN-Sf
      protein. The Tn5 insertion mutants of YSH6000 possessing phoN-Sf::Tn5 still
      retained wild-type levels of invasiveness, as well as the subsequent spreading
      capacity in MK2 epithelial cell monolayers, thus suggesting that the PhoN-Sf
      activity is not involved in expression of the virulence phenotypes of Shigella
      strains under in vitro conditions.

PMID- 8755884
TI  - Respiratory control determines respiration and nitrogenase activity of Rhizobium
      leguminosarum bacteroids.
AB  - The relationship between the O2 input rate into a suspension of Rhizobium
      leguminosarum bacteroids, the cellular ATP and ADP pools, and the whole-cell
      nitrogenase activity during L-malate oxidation has been studied. It was observed
      that inhibition of nitrogenase by excess O2 coincided with an increase of the
      cellular ATP/ADP ratio. When under this condition the protonophore carbonyl
      cyanide m-chlorophenylhydrazone (CCCP) was added, the cellular ATP/ADP ratio was
      lowered while nitrogenase regained activity. To explain these observations, the
      effects of nitrogenase activity and CCCP on the O2 consumption rate of R.
      leguminosarum bacteroids were determined. From 100 to 5 microM O2, a decline in
      the O2 consumption rate was observed to 50 to 70% of the maximal O2 consumption
      rate. A determination of the redox state of the cytochromes during an O2
      consumption experiment indicated that at O2 concentrations above 5 microM,
      electron transport to the cytochromes was rate-limiting oxidation and not the
      reaction of reduced cytochromes with oxygen. The kinetic properties of the
      respiratory chain were determined from the deoxygenation of oxyglobins. In intact
      cells the maximal deoxygenation activity was stimulated by nitrogenase activity
      or CCCP. In isolated cytoplasmic membranes NADH oxidation was inhibited by
      respiratory control. The dehydrogenase activities of the respiratory chain were
      rate-limiting oxidation at O2 concentrations (if >300 nM. Below 300 nM the
      terminal oxidase system followed Michaelis-Menten kinetics (Km of 45 +/- 8 nM).
      We conclude that (i) respiration in R. leguminosarum bacteroids takes place via a
      respiratory chain terminating at a high-affinity oxidase system, (ii) the
      activity of the respiratory chain is inhibited by the proton motive force, and
      (iii) ATP hydrolysis by nitrogenase can partly relieve the inhibition of
      respiration by the proton motive force and thus stimulate respiration at
      nanomolar concentrations of O2.

PMID- 8755885
TI  - The molecular architecture of the sar locus in Staphylococcus aureus.
AB  - The global regulator sar in Staphylococcus aureus controls the synthesis of a
      variety of cell wall and extracellular proteins, many of which are putative
      virulence factors. The sar locus in strain RN6390 contains a 339-bp open reading
      frame (sarA) and an 860-bp upstream region. Transcriptional analyses of this
      locus revealed three different transcripts of 0.58, 0.84, and 1.15 kb (designated
      sarA, sarC, and sarB, respectively). All three transcripts seemed to be under
      temporal, growth cycle-dependent regulation, with sarA and sarB being most
      abundant in early log phase and the sarC concentration being highest toward the
      late stationary phase. Mapping of the 5' ends of the sar transcripts by primer
      extension and modified S1 nuclease protection assays demonstrated that
      transcription is initiated from three separate, widely spaced promoters. The 3'
      ends of all three sar transcripts are identical, and transcriptional termination
      occurs upstream of a typical prokaryotic poly(T) termination signal. Northern
      (RNA) analysis of sar mutant clones containing plasmids that comprised various
      promoters and the termination signal revealed that individual transcripts can be
      generated from each of the three promoters, thus suggesting possible activation
      as independent promoters. The multipromoter system, from which transcription is
      initiated, bears conserved features for recognition by homologous sigma 70
      transcription factors and also by those expressed in the general stress response.
      Downstream of the two distal promoters (P3 and P2) are two regions potentially
      encoding short peptides. It is conceivable that posttranslational cooperation
      between these short peptides and the sarA gene product occurs to modulate sar
      related functions. Complementation studies of a sar mutant with a clone
      expressing all three sar transcripts showed that this clone was able to restore
      the sar wild-type phenotype to the sar mutant.

PMID- 8755886
TI  - Cloning, complementation, and characterization of an rfaE homolog from Neisseria
      gonorrhoeae.
AB  - Neisseria gonorrhoeae WS1 is a spontaneous pyocin (a bacteriocin produced by
      Pseudomonas aeruginosa)-resistant mutant of N. gonorrhoeae FA19 that produces a
      truncated lipooligosaccharide (LOS) and is non-transformable. The LOS-specific
      mutation in WS1 was moved into a transformable background by transforming FA19
      with chromosomal DNA from WS1 (generating strain JWS-1). A clone (pJCL2) capable
      of restoring JWS-1 to wild-type LOS expression, as detected by its acquisition of
      reactivity with monoclonal antibodies and by its complemented sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis profile, was isolated. Sequential
      unidirectional deletion and DNA sequence analysis of pJCL2 identified an open
      reading frame, designated lsi-7, that could complement the defect in JWS-1.
      Homology searches against various databases indicated that lsi-7 bad homology
      with several Escherichia coli genes involved in the phosphorylation of sugars.
      lsi-7 is adjacent to the lsi-6 gene, another gene involved in LOS biosynthesis.
      Complementation studies using Salmonella typhimurium lipopolysaccharide mutants
      showed lsi-6 and lsi-7 to be gonococcal homologs of S. typhimurium rfaD and rfaE,
      respectively. Reverse transcriptase PCR analysis demonstrated that lsi-6 and lsi
      7 are part of the same transcriptional unit.

PMID- 8755887
TI  - Expression of the tre operon of Bacillus subtilis 168 is regulated by the
      repressor TreR.
AB  - The tre locus from Bacillus subtilis containing the genes treP, treA, and treR
      has been analyzed for its regulation. We demonstrate that at least treP and treA
      form an operon whose expression is regulated at the transcriptional level. TreR
      activity has been investigated in in vivo and in vitro studies. An insertional
      inactivation of treR led to a constitutive expression of treP and treA. Upstream
      of treP we identified a 248-bp DNA fragment containing a potential sigmaA
      dependent promoter and two palindromes reflecting potential tre operators which
      led to complex formation with TreR-containing protein extracts in DNA retardation
      experiments. This complex formation is abolished in the presence of trehalose-6
      phosphate, which probably acts as an inducer. Therefore, we assume that treR
      encodes the specific Tre repressor involved in regulation of the expression of
      the tre operon.

PMID- 8755889
TI  - At least two separate gene clusters are involved in albicidin production by
      Xanthomonas albilineans.
AB  - Transposon mutagenesis was used to obtain mutations affecting production of the
      toxin albicidin in Xanthomonas albilineans, which causes leaf scald disease of
      sugarcane and is also pathogenic to corn. Transposon Tn5-gusA inserted randomly
      into genomic DNA of X. albilineans Xa23R1 at a frequency of 10(-4) to 10(-5) per
      recipient after conjugal transfer from Escherichia coli. Fifty prototrophic
      mutants defective in albicidin production were isolated from 7,100 Tn5-gusA
      insertional derivatives tested for toxin production by an antibiosis bioassay.
      EcoRI fragments containing Tn5 flanking sequences from two mutants (AM15 and
      AM40) were cloned and used to probe a wild-type Xa23R1 DNA library by colony
      hybridization. Nine cosmids showed homology to the AM15 probe, and six showed
      homology to the AM40 probe. Four cosmid clones hybridized to both probes. Forty
      five of the 50 defective mutants were restored to albicidin production with two
      overlapping cosmid clones. Restriction mapping showed that these mutants span a
      genomic region of about 48 kb. At least one other gene cluster is also involved
      in albicidin production in Xa23R1. DNA fragments from the 48-kb cluster proved to
      be very specific to X. albilineans. Some mutants affected in albicidin production
      retain their ability to colonize sugarcane cultivated in vitro.

PMID- 8755888
TI  - Analysis of a FliM-FliN flagellar switch fusion mutant of Salmonella typhimurium.
AB  - In the course of an analysis of the three genes encoding the flagellar motor
      switch, we isolated a paralyzed mutant whose defect proved to be a 4-bp deletion
      of the ribosome binding sequence of the fliN switch gene (V. M. Irikura, M.
      Kihara, S. Yamaguchi, H. Sockett, and R. M. Macnab, J. Bacteriol. 175:802
      810,1993). This sequence lies just before the 3' end of the coding sequence of
      the upstream fliM switch gene, in the same operon. This mutant readily gave rise
      to pseudorevertants which, though much less motile than the wild type, did
      exhibit significant swarming. One such pseudorevertant was found to contain a
      compensating frameshift such that the fliM and fliN genes were placed in frame,
      coding for an essentially complete FliM-FliN protein fusion. Minicell analysis
      demonstrated that, as expected, the parental mutant synthesized an essentially
      full-length FliM protein but no detectable FliN. The pseudorevertant, in
      contrast, synthesized a protein with the predicted size for the FliM-FliN fusion
      protein and no detectable FliM or FliN. Immunoblotting of minicells with
      antibodies against FliM and FliN confirmed the identities of these various
      proteins. Immunoblotting of book-basal-body complexes from the wild-type strain
      gave a strong signal for the three switch proteins FliG, FliM, and FliN.
      Complexes from the FliM-FliN fusion mutant gave a strong signal for FliG but no
      signal for either FIiM or FliN; a moderately strong signal for the FliM-FliN
      fusion protein was seen with the anti-FliM antibody, and a weaker signal was seen
      with the anti-FliN antibody. The cytoplasmic C ring of the structure, which is
      seen consistently in electron microscopy of wild-type complexes and which is
      known to contain the FliM and FliN proteins, was much more labile in the FliM
      FliN fusion mutant, giving a fragmented and variable appearance or being
      completely absent. Complementation data indicated that wild-type FliM had a mild
      dominant negative effect over the fusion protein, that wild-type FliN and the
      fusion protein work much better than the fusion protein alone, and that wild-type
      FliM and FliN together have no major positive or negative effect on the function
      of the fusion protein. We interpret these data to mean that the FliM-FliN fusion
      protein incorporates into structure but less stably than do the FliM and FliN
      proteins separately, that wild-type FliM tends to displace the fusion protein,
      and that wild-type FliN can supplement the FliN domain of the fusion protein
      without displacing the FliM domain. The data support, but do not prove, a model
      in which FliM and FliN in the wild-type switch complex are stationary with
      respect to each other.

PMID- 8755890
TI  - Effect of nitrate on the autotrophic metabolism of the acetogens Clostridium
      thermoautotrophicum and Clostridium thermoaceticum.
AB  - Although nitrate stimulated the capacity of Clostridium thermoautotrophicum and
      Clostridium thermoaceticum to oxidize (utilize) substrates under heterotrophic
      conditions, it inhibited autotrophic H2-CO2-dependent growth. Under basal medium
      conditions, nitrate was also inhibitory to the use of one-carbon substrates
      (i.e., CO, formate, methanol, or the O-methyl groups of vanillate or syringate)
      as sole carbon energy sources. This inhibitory effect of nitrate was bypassed
      when both O-methyl groups and CO were provided concomitantly; H2-CO2 did not
      replace CO. These results indicated that nitrate blocked the reduction of CO2 to
      the methyl and carbonyl levels. On the basis of the inability of acetogenic cells
      (i.e., cells cultivated without nitrate) to consume or reduce nitrate in resting
      cell assays, the capacity to dissimilate nitrate was not constitutive. Nitrate
      had no appreciable effect on the specific activities of enzymes central to the
      acetyl-coenzyme A (CoA) pathway. However, membranes obtained from cells
      cultivated under nitrate-dissimilating conditions were deficient in the b-type
      cytochrome that was typical of membranes from acetogenic cells, i.e., cells
      dependent upon the synthesis of acetate for the conservation of energy.
      Collectively, these findings indicated that (i) C. thermoautotrophicum and C.
      thermoaceticum cannot engage the carbon-fixing capacities of the acetyl-CoA
      pathway in the presence of nitrate and (ii) the nitrate block on the acetyl-CoA
      pathway occurs via an alteration in electron transport.

PMID- 8755891
TI  - Cloning and characterization of the metE gene encoding S-adenosylmethionine
      synthetase from Bacillus subtilis.
AB  - The metE gene, encoding S-adenosylmethionine synthetase (EC 2.5.1.6) from
      Bacillus subtilis, was cloned in two steps by normal and inverse PCR. The DNA
      sequence of the metE gene contains an open reading frame which encodes a 400
      amino-acid sequence that is homologous to other known S-adenosylmethionine
      synthetases. The cloned gene complements the metE1 mutation and integrates at or
      near the chromosomal site of metE1. Expression of S-adenosylmethionine synthetase
      is reduced by only a factor of about 2 by exogenous methioinine. Overproduction
      of S-adenosylmethionine synthetase from a strong constitutive promoter leads to
      methionine auxotrophy in B. subtilis, suggesting that S-adenosylmethionine is a
      corepressor of methionine biosynthesis in B. subtilis, as others have already
      shown for Escherichia coli.

PMID- 8755892
TI  - Cold shock stress-induced proteins in Bacillus subtilis.
AB  - Bacteria respond to a decrease in temperature with the induction of proteins that
      are classified as cold-induced proteins (CIPs). Using two-dimensional gel
      electrophoresis, we analyzed the cold shock response in Bacillus subtilis. After
      a shift from 37 to 15 degrees C the synthesis of a majority of proteins was
      repressed; in contrast, 37 proteins were synthesized at rates higher than
      preshift rates. One hour after cold shock, the induction of CIPs decreased, and
      after 2 h, general protein synthesis resumed. The identified main CIPs were
      excised from two-dimensional gels and were subjected to microsequencing. Three
      small acidic proteins that showed the highest relative induction after cold shock
      were highly homologous and belonged to a protein family of which one member, the
      major cold shock protein, CspB, has previously been characterized. Two
      dimensional gel analyses of a cspB null mutant revealed that CspB affects the
      level of induction of several CIPs. Other identified CIPs function at various
      levels of cellular physiology, such as chemotaxis (CheY), sugar uptake (Hpr),
      translation (ribosomal proteins S6 and L7/L12), protein folding (PPiB), and
      general metabolism (CysK, Ilvc, Gap, and triosephosphate isomerase).

PMID- 8755893
TI  - Defect in general priming conferred by linker region mutants of Escherichia coli
      dnaB.
AB  - The dnaB gene of Escherichia coli encodes a bifunctional primase accessory
      protein/helicase necessary for chromosomal replication. Monomers of DnaB comprise
      two trypsin-resistant domains connected by a 45-amino-acid linker. To investigate
      the role of the linker in the structure and function of DnaB, we have purified
      and characterized three DnaB mutant proteins having single amino acid
      substitutions in the linker. We find that the mutant proteins retain the two
      domain structure and assemble into hexamers that may be less stable than hexamers
      formed by wild-type DnaB. These mutant hexamers have hydrodynamic properties
      slightly different from those of the wild type, suggestive of a more open
      structure. The mutant proteins had reduced or absent ability to stimulate primase
      and also exhibited slight alterations in ATPase activity compared with the wild
      type. We conclude that the linker region promotes primase-DnaB interaction, but
      this effect may be indirect. We propose a model involving repositioning of N
      terminal domains to explain the properties of the mutant proteins.

PMID- 8755894
TI  - Organization, transcription, and expression of the 5' region of the fla operon of
      Treponema phagedenis and Treponema pallidum.
AB  - A locus encoding polypeptides associated with flagellar structure and function
      was identified, sequenced, and characterized in Treponema phagedenis and
      Treponema pallidum. This locus includes homologs of the FlgD, FlgE, MotA, MOB,
      FliL, and FliM polypeptides found in Salmonella typhimurium and Bacillus
      subtilis. These polypeptides are extensively conserved between the two
      treponemes. Several additional polypeptides or unknown function, including Tapl,
      located upstream of FlgD, and ORF4, located between FlgE and MotA, were also
      identified. Transcription analysis using RNA PCR indicated that these genes are
      likely transcribed as part of a single operon and comprise the 5' region of the
      treponemal fla operon. Primer extension analysis identified a putative promoter,
      preceding T. phagedenis tap1 in a region of divergent transcription. Pfla
      resembles the class II or class III motility-related promoters of S. typhimurium.
      FlgE and Tap1 were further characterized. Western blotting (immunoblotting)
      indicated that T. pallidum FlgE exhibited an unusual polypeptide ladder that was
      similar but not identical to that of T. phagedenis. Triton X-114 phase
      partitioning of T. phagedenis cells coupled with Western blotting revealed that
      Tap1 was located in the aqueous phase. Computer analysis indicated that Tap1 had
      no significant membrane spanning regions, suggesting that it resides primarily in
      the cytoplasm. The organization and expression of this operon are similar in both
      treponemes but different from those of previously described motility-related
      operons. These results indicate that despite extensive amino acid sequence
      conservation, the expression of spirochete flagellar polypeptides is different
      from that in other bacteria.

PMID- 8755895
TI  - Beta-glucan synthesis in Bradyrhizobium japonicum: characterization of a new
      locus (ndvC) influencing beta-(1-->6) linkages.
AB  - Bradyrhizobium japonicum synthesizes periplasmic cyclic beta-(1-->3),beta-(1-->6)
      D-glucans during growth in hypoosmotic environments, and evidence is growing that
      these molecules may have a specific function during plant-microbe interactions in
      addition to osmoregulation. Site-directed Tn5 mutagenesis of the DNA region
      upstream of ndvB resulted in identification of a new gene (ndvC) involved in beta
      (1--> 3), beta-(1-->6)-glucan synthesis and in nodule development. The predicted
      translation product was a polypeptide (ca. 62 kDa) with several transmembrane
      domains. It contained a sequence characteristic of a conserved nucleoside-sugar
      binding motif found in many bacterial enzymes and had 51% similarity with a beta
      glucanosyltransferase from Candida albicans. B. japonicum carrying a Tn5
      insertion in ndvC resulted in synthesis of altered cyclic beta-glucans composed
      almost entirely of beta-(1--> 3)-glycosyl linkages. The mutant strain was only
      slightly sensitive to hypoosmotic growth conditions compared with the ndvB
      mutant, but it was severely impaired in symbiotic interactions with soybean
      (Glycine max). Nodulation was delayed by 8 to 10 days, and many small nodule-like
      structures apparently devoid of viable bacteria were formed. This finding
      suggests that the structure of the beta-glucan molecule is important for a
      successful symbiotic interaction, and beta-glucans may have a specific function
      in addition to their role in hypoosmotic adaptation.

PMID- 8755896
TI  - Bald mutants of Streptomyces griseus that prematurely undergo key events of
      sporulation.
AB  - To identify the structural defects of nonsporulating mutants of Streptomyces
      griseus, the wild-type strain and class III bald mutants were examined by using
      transmission electron microscopy, ultrasonic treatment, and fluorescence
      microscopy after the induction of submerged sporulation by phosphate starvation.
      In the wild-type strain, submerged sporulation was marked by the relatively
      synchronous formation of sporogenic hyphae, nucleoid segregation, deposition of
      sporulation septa, and subsequent thickening of the spore walls during
      maturation. All of the class III mutants prematurely synthesized sporulation
      septa and thick spore walls. The class IIIA and C mutants formed sporogenic
      hyphae earlier than the wild-type strain and underwent nucleoid segregation in
      parallel with sporulation septum formation. In the class IIIB (bld4) mutant, DNA
      segregation appeared to be uncoupled from septum formation. The results indicate
      that the class III mutants are defective in loci that are involved in the
      regulation of key events of Streptomyces morphogenesis.

PMID- 8755897
TI  - Mutational analysis of a transmembrane segment in a bacterial chemoreceptor.
AB  - Trg is a member of a family of receptors that mediates chemotaxis by Escherichia
      coli. Its transmembrane domain is a loose four-helix bundle consisting of two
      helices from each of the two identical subunits. This domain mediates
      transmembrane signaling through a conformational change in which the second
      transmembrane segment (TM2) is thought to move relative to TM1, but mutational
      analysis of TM2 by cysteine scanning had identified only a few positions at which
      substitutions perturbed function or induced signaling. Thus, we performed
      mutational analysis by random mutagenesis and screening. Among 42 single-residue
      substitutions in TM2 that detectably altered function, 16 had drastic effects on
      receptor activity. These substitutions defined a helical face of TM2. This
      functionally important surface was directed into the protein interior of the
      transmembrane domain, where TM2 faces the helices or the other subunit. The
      functionally perturbing substitutions did not appear to cause general disruption
      of receptor structure but rather had more specific effects, altering aspects of
      transmembrane signaling. An in vivo assay of signaling identified some
      substitutions that reduced and others that induced signaling. These two classes
      were distributed along adjacent helical faces in a pattern that strongly supports
      the notion that conformational signaling involves movement between TM2 and TM1
      and that signaling is optimal when stable interactions are maintained across the
      interface between the homologous helices in the transmembrane domain. Our
      mutational analysis also revealed a striking tolerance of the chemoreceptor for
      substitutions, including charged residues, usually considered to be disruptive of
      transmembrane segments.

PMID- 8755898
TI  - Spontaneous and induced mutations in a single open reading frame alter both
      virulence and avirulence in Xanthomonas campestris pv. vesicatoria avrBs2.
AB  - Molecular characterization of the avrBs2 locus from Xanthomonas campestris pv.
      vesicatoria has revealed that expression of this gene triggers disease resistance
      in Bs2 pepper (Capsicum annuum) plants and contributes to virulence of the
      pathogen. Deletion analysis and site-directed mutagenesis established the avrBs2
      gene as a 2,190-bp open reading frame encoding a putative 80.1-kDa protein. Two
      classes of Xanthomonas pathogens evading Bs2 host resistance and displaying
      reduced fitness were found to be specifically mutated in avrBs2. Members of one
      class contained a 5-bp insertion, while the second class was distinguished by a
      divergent 3' region of avrBs2; both mutant classes were complemented in trans by
      a plasmid-borne copy of avrBs2. A divergent avrBs2 homolog was cloned from the
      Brassica pathogen X. campestris pv. campestris. The predicted AvrBs2 proteins
      from the two Xanthomonas pathovars were strongly conserved and had predicted
      sequence similarity with both Agrobacterium tumefaciens agrocinopine synthase and
      Escherichia coli UgpQ, two enzymes involved in the synthesis or hydrolysis of
      phosphodiester linkages. On the basis of homology with agrocinopine synthase and
      UgpQ and the dual phenotype of avirulence and virulence, several models for the
      function of AvrBs2 are proposed.

PMID- 8755899
TI  - HmbR outer membrane receptors of pathogenic Neisseria spp.: iron-regulated,
      hemoglobin-binding proteins with a high level of primary structure conservation.
AB  - We have recently cloned and characterized the hemoglobin receptor gene from
      Neisseria meningitidis serogroup C. N. meningitidis cells expressing HmbR protein
      were able to bind biotinylated hemoglobin, and the binding was specifically
      inhibited by unlabeled hemoglobin and not heme. The HmbR-mediated hemoglobin
      binding activity of N. meningitidis cells was shown to be iron regulated. The
      presence of hemoglobin but not heme in the growth medium stimulated HmbR-mediated
      hemoglobin binding activity. The efficiency of utilization of different
      hemoglobins by the HmbR-expressing N. meningitidis cells was shown to be species
      specific; human hemoglobin was the best source of iron, followed by horse, rat,
      turkey, dog, mouse, and sheep hemoglobins, The phenotypic characterization of
      HmbR mutants of some clinical strains of N. meningitidis suggested the existence
      of two unrelated hemoglobin receptors. The HmbR-unrelated hemoglobin receptor was
      shown to be identical to Hpu, the hemoglobin-haptoglobin receptor of N.
      meningitidis. The Hpu-dependent hemoglobin utilization system was not able to
      distinguish between different sources of hemoglobin; all animal hemoglobins were
      utilized equally well. HmbR-like genes are also present in N. meningitidis
      serogroups A and B, Neisseria gonorrhoeae MS11 and FA19, Neisseria perflava, and
      Neisseria polysaccharea. The hemoglobin receptor genes from N. meningitidis
      serogroups A and B and N. gonorrhoeae MS11 were cloned, and their nucleotide
      sequences were determined. The nucleotide sequence identity ranged between 86.5%
      (for N. meningitidis serogroup B hmbR and MS11 hmbR) and 93.4% (for N.
      meningitidis serogroup B hmbR and N. meningitidis serogroup C hmbR). The deduced
      amino acid sequences of these neisserial hemoglobin receptors were also highly
      related, with overall 84.7% conserved amino acid residues. A stop codon was found
      in the hmbR gene of N. gonorrhoeae MS11. This strain was still able to use
      hemoglobin and hemoglobin-haptoglobin complexes as iron sources, indicating that
      some gonococci may express only the HmbR-independent hemoglobin utilization
      system.

PMID- 8755900
TI  - Iron is required to relieve inhibitory effects on NifL on transcriptional
      activation by NifA in Klebsiella pneumoniae.
AB  - In Klebsiella pneumoniae, products of the nitrogen fixation nifLA operon regulate
      transcription of the other nif operons. NifA activates transcription by sigma54
      holoenzyme. In vivo, NifL antagonizes the action of NifA under aerobic conditions
      or in the presence of combined nitrogen. In contrast to a previous report, we
      show that depletion of iron (Fe) from the growth medium with the chelating agent
      o-phenanthroline (20 microM) mimics aerobiosis or combined nitrogen in giving
      rise to inhibition of NifA activity even under anaerobic, nitrogen-limiting
      conditions. Adding back Fe in only twofold molar excess over phenanthroline
      restores NifA activity, whereas adding other metals fails to do so. By using
      strains that lack NifL, we showed that NifA activity itself does not require Fe
      and is not directly affected by phenanthroline. Hence, Fe is required to relieve
      the inhibition of NifA activity by NifL in vivo. Despite the Fe requirement in
      vivo, we have found no evidence that NifL contains Fe or an iron-sulfur (Fe-S)
      cluster. Determination of the molecular mass of an inhibitory form of NifL
      overproduced under aerobic conditions indicated that it was not
      posttranslationally modified. When NifL was synthesized in vitro, it inhibited
      transcriptional activation by NifA even when it was synthesized under anaerobic
      conditions in the presence of a high Fe concentration or of superoxide dismutase,
      which is known to protect some Fe-S clusters. Moreover, overproduction of
      superoxide dismutase in vivo did not relieve NifL, inhibition under aerobic
      conditions, and attempts to relieve NifL inhibition in vitro by reconstituting Fe
      S clusters with the NifS enzyme (Azotobacter vinelandii) were unsuccessful. Since
      we obtained no evidence that Fe acts directly on NifL or NifA, we postulate that
      an additional Fe-containing protein, not yet identified, may be required to
      relieve NifL inhibition under anaerobic, nitrogen-limiting conditions.

PMID- 8755901
TI  - Insertional inactivation of Streptococcus pyogenes sod suggests that prtF is
      regulated in response to a superoxide signal.
AB  - In establishing an infection, Streptococcus pyogenes has the capacity to bind to
      the host extracellular matrix protein fibronectin via its protein F adhesin.
      Previous studies have suggested that the expression of protein F is stimulated
      during aerobic growth or upon addition of superoxide-generating agents to the
      culture under O2-limited conditions. To further explore the role of superoxide,
      we have examined the transcription of the gene which encodes protein F (prtF), as
      well as the expression of superoxide dismutase (SOD) under conditions which
      promote or repress protein F expression. These studies show that prtF
      transcription is regulated in response to superoxide concentration and that SOD
      is regulated in different environments in a manner which directly parallels the
      expression of protein F. A mutant deficient in SOD activity was constructed by
      insertional mutation into the gene which encodes SOD (sod). The resulting mutant
      was sensitive to superoxide and aerobic conditions, showed hypersensitive
      induction of prtF in response to superoxide, and expressed prtF under normally
      unfavorable O2-limited conditions. These findings suggest that a streptococcal
      signal transduction system which senses superoxide may coordinately control
      expression of prtF and sod.

PMID- 8755902
TI  - Peptidoglycan synthesis and structure in Staphylococcus haemolyticus expressing
      increasing levels of resistance to glycopeptide antibiotics.
AB  - The structures of cytoplasmic peptidoglycan precursor and mature peptidoglycan of
      an isogenic series of Staphylococcus haemolyticus strains expressing increasing
      levels of resistance to the glycopeptide antibiotics teicoplanin and vancomycin
      (MICs, 8 to 32 and 4 to 16 microg/ml, respectively) were determined. High
      performance liquid chromatography, mass spectrometry, amino acid analysis,
      digestion by R39 D,D-carboxypeptidase, and N-terminal amino acid sequencing were
      utilized. UDP-muramyl-tetrapeptide-D-lactate constituted 1.7% of total
      cytoplasmic peptidoglycan precursors in the most resistant strain. It is not
      clear if this amount of depsipeptide precursor can account for the levels of
      resistance achieved by this strain. Detailed structural analysis of mature
      peptidoglycan, examined for the first time for this species, revealed that the
      peptidoglycan of these strains, like that of other staphylococci, is highly cross
      linked and is composed of a lysine muropeptide acceptor containing a substitution
      at its epsilon-amino position of a glycine-containing cross bridge to the D-Ala 4
      of the donor, with disaccharide-pentapeptide frequently serving as an acceptor
      for transpeptidation. The predominant cross bridges were found to be COOH-Gly-Gly
      Ser-Gly-Gly-NH2 and COOH-Ala-Gly-Ser-Gly-Gly-NH2. Liquid chromatography-mass
      spectrometry analysis of the peptidoglycan of resistant strains revealed
      polymeric muropeptides bearing cross bridges containing an additional serine in
      place of glycine (probable structures, COOH-Gly-Ser-Ser-Gly-Gly-NH2 and COOH-Ala
      Gly-Ser-Ser-Gly-NH2). Muropeptides bearing an additional serine in their cross
      bridges are estimated to account for 13.6% of peptidoglycan analyzed from
      resistant strains of S. haemolyticus. A soluble glycopeptide target (L-Ala-gamma
      D-iso-glutamyl-L-Lys-D-Ala-D-Ala) was able to more effectively compete for
      vancomycin when assayed in the presence of resistant cells than when assayed in
      the presence of susceptible cells, suggesting that some of the resistance was
      directed towards the cooperativity of glycopeptide binding to its target. These
      results are consistent with a hypothesis that alterations at the level of the
      cross bridge might interfere with the binding of glycopeptide dimers and
      therefore with the cooperative binding of the antibiotic to its target in situ.
      Glycopeptide resistance in S. haemolyticus may be multifactorial.

PMID- 8755903
TI  - Regulated expression of a repressor protein: FadR activates iclR.
AB  - The control of the glyoxylate bypass operon (aceBAK) of Escherichia coli is
      mediated by two regulatory proteins, IclMR and FadR. IclMR is a repressor protein
      which has previously been shown to bind to a site which overlaps the aceBAK
      promoter. FAR is a repressor/activator protein which participates in control of
      the genes of fatty acid metabolism. A sequence just upstream of the iclR promoter
      bears a striking resemblance to FadR binding sites found in the fatty acid
      metabolic genes. The in vitro binding specificity of FadR, determined by
      oligonucleotide selection, was in good agreement with the sequences of these
      sites. The ability of FadR to bind to the site associated with iclR was
      demonstrated by gel shift and DNase I footprint analyses. Disruption of FadR or
      inactivation of the FadR binding site of iclR decreased the expression of an
      iclR::lacZ operon fusion, indicating that FadR activates the expression of iclR.
      It has been reported that disruption of fadR increases the expression of aceBAK.
      We observed a similar increase when we inactivated the FadR binding site of an
      iclR+ allele. This result suggests that FadR regulates aceBAK indirectly by
      altering the expression of IclR.

PMID- 8755904
TI  - Pleiotropic phenotypes caused by genetic ablation of the receiver module of the
      Agrobacterium tumefaciens VirA protein.
AB  - The VirA protein of Agrobacterium tumefaciens is a transmembrane sensory kinase
      that phosphorylates the VirG response regulator in response to chemical signals
      released from plant wound sites. VirA contains both a two-component kinase module
      and, at its carboxyl terminus, a receiver module. We previously provided evidence
      that this receiver module inhibited the activity of the kinase module and that
      inhibition might be neutralized by phosphorylation. In this report, we provide
      additional evidence for this model by showing that overexpressing the receiver
      module in trans can restore low-level basal activity to a VirA mutant protein
      lacking the receiver module. We also show that ablation of the receiver module
      restores activity to the inactive VirA (delta324-413) mutant, which has a
      deletion within a region designated the linker module. This indicates that
      deletion of the linker module does not denature the kinase module, but rather
      locks the kinase into a phenotypically inactive conformation, and that this
      inactivity requires the receiver module. These data provide genetic evidence that
      the kinase and receiver modules of VirA attain their native conformations
      autonomously. The receiver module also restricts the variety of phenolic
      compounds that have stimulatory activity, since removal of this module causes
      otherwise nonstimulatory phenolic compounds such as 4-hydroxyacetophenone to
      stimulate vir gene expression.

PMID- 8755905
TI  - Resection and mutagenesis of the acid pH-inducible P2 promoter of the
      Agrobacterium tumefaciens virG gene.
AB  - Transcription of the virG gene initiates from two tandem promoters, designated P1
      and P2, that are located 50 nucleotides apart. Transcription of the P2 promoter
      is induced by extracellular acidity. cis-acting sites required for P2 activity
      were identified by constructing and assaying a series of 5' and 3' resections and
      site-directed nucleotide substitutions. Nucleotides between positions -9 and -37
      were sufficient for regulated promoter activity. Within this region, nucleotide
      substitutions at the predicted -10 and -35 regions strongly reduced P2
      expression. In addition, alterations in the region between nucleotides -24 and 
      32 also eliminated or strongly reduced promoter activity. These data suggest that
      this promoter may be regulated by a positive transcription factor that binds to
      nucleotide residues in this interval.

PMID- 8755906
TI  - Glucose repression may involve processes with different sugar kinase
      requirements.
AB  - Adding glucose to Saccharomyces cerevisiae cells growing among nonfermentable
      carbon sources leads to glucose repression. This process may be resolved into
      several steps. An early repression response requires any one of the three glucose
      kinases present in S. cerevisiae (HXK1, HXK2, or GLK1). A late response is only
      achieved when Hxk2p is present.

PMID- 8755907
TI  - Members of the Hsp70 family of proteins in the cell wall of Saccharomyces
      cerevisiae.
AB  - Western blot (immunoblot) analysis of cell wall and cytosolic extracts obtained
      from parental and ssa1 and ssa2 single- and double-mutant strains of
      Saccharomyces cerevisiae showed that the heat shock protein 70 (Hsp70) products
      of these genes, previously thought to be restricted to the cell interior, are
      also present in the cell wall. A cell wall location was further confirmed by
      indirect immunofluorescence with intact cells and biotinylation of extracellular
      Hsp70. Hsp70s have been implicated in translocation across the membrane and as
      molecular chaperones, and changes in the profile of cell wall proteins suggested
      that these proteins may have a similar role in the cell wall.

PMID- 8755908
TI  - The genes for phosphofructokinase and pyruvate kinase of Lactobacillus
      delbrueckii subsp. bulgaricus constitute an operon.
AB  - In Lactobacillus delbrueckii subsp. bulgaricus, the pyk gene coding for pyruvate
      kinase and the pfk gene coding for phosphofructokinase formed a bicistronic
      operon transcribed into a 2.9-kb RNA. The nucleotide sequence of the pyk gene
      indicated that the encoded protein possessed an extra C-terminal domain with a
      potential phosphoenolpyruvate-dependent autophosphorylation site.

PMID- 8755909
TI  - Conversion of NfsB, a minor Escherichia coli nitroreductase, to a flavin
      reductase similar in biochemical properties to FRase I, the major flavin
      reductase in Vibrio fischeri, by a single amino acid substitution.
AB  - NfsB is an oxygen-insensitive nitroreductase of Escherichia coli with significant
      amino acid sequence homology to the major flavin reductase (FRase I) of Vibrio
      fischeri. Here, we show that NfsB is convertible to an FRase I-like flavin
      reductase three times as active as the authentic FRase I by a single amino acid
      substitution in the least-conserved region.

PMID- 8755910
TI  - Interaction of the GATA factor Gln3p with the nitrogen regulator Ure2p in
      Saccharomyces cerevisiae.
AB  - We used cells carrying plasmids causing the overproduction of Gln3p, Ure2p, or
      both of these proteins to elucidate the ability of Ure2p to prevent the
      activation of gene expression by Gln3p in cells growing in a glutamine-containing
      medium. Our results indicate that Ure2p probably does not interfere with the
      binding of the GATA factor Gln3p to GATAAG sites but acts directly on Gln3p to
      block its ability to activate transcription.

PMID- 8755911
TI  - Conserved sequence elements involved in regulation of ribosomal protein gene
      expression in halophilic archaea.
AB  - A region of the Haloferax volcanii genome encoding ribosomal proteins L11e, L1e,
      L10e, and L12e was cloned and sequenced, and the transcripts derived from the
      cluster were characterized. Flanking and noncoding regions of the sequence were
      analyzed phylogenetically by comparison with the homologous sequences from two
      other halophilic archaea, i.e., Halobacterium cutirubrum and Haloarcula
      marismortui. Motifs, identified by high-level sequence conservation, include both
      transcriptional and translational regulatory elements and other elements of
      unknown function.

PMID- 8755912
TI  - Glutathione amide and its perthiol in anaerobic sulfur bacteria.
AB  - Chromatium species produced the novel biological thiol glutathione amide, gamma-L
      glutamyl-L-cysteinylglycine amide (GASH), when grown photoheterotrophically. GASH
      was largely converted to the corresponding perthiol during photoautotrophic
      growth on sulfide, suggesting that GASH may have a function in anaerobic sulfide
      metabolism. This unprecedented form of glutathione metabolism was probably
      present in anaerobic ancestors of modern cyanobacteria and purple bacteria.

PMID- 8755913
TI  - Analysis of the enzymatic cleavage (beta elimination) of the capsular K5
      polysaccharide of Escherichia coli by the K5-specific coliphage: reexamination.
AB  - The capsular K5 polysaccharide of Escherichia coli is the receptor of the capsule
      specific coliphage K5, which harbors an enzyme that degrades the capsular K5
      polysaccharide to a number of oligosaccharides. Analysis of the degradation
      products using gel permeation chromatography, the periodate-thiobarbituric acid
      and bicinchoninic acid reactions, and nuclear magnetic resonance spectroscopy
      showed that the major reaction products are hexa-, octa-, and decasaccharides
      with 4,5-unsaturated glucuronic acid (delta4,5GlcA) at their nonreducing end.
      Thus, the bacteriophage enzyme is a K5 polysaccharide lyase and not, as we had
      reported previously, an endo-N-acetylglucosaminidase.

PMID- 8755914
TI  - Nucleotide sequence of a beta-1,3-glucanase isoenzyme IIA gene of Oerskovia
      xanthineolytica LL G109 (Cellulomonas cellulans) and initial characterization of
      the recombinant enzyme expressed in Bacillus subtilis.
AB  - The nucleotide sequence of the betaglIIA gene, encoding the extracellular beta
      1,3-glucanase IIA (betaglIIA) of the yeast-lytic actinomycete Oerskovia
      xanthineolytica LL G109, was determined. Sequence comparison shows that the
      betaglIIA enzyme has over 80% identity to the betaglII isoenzyme, an endo-beta
      1,3-glucanase having low yeast-lytic activity secreted by the same bacterium. The
      betaglIIA enzyme lacks a glucan- or mannan-binding domain, such as those observed
      in beta-1,3-glucanases and proteases having high yeast/fungus-lytic activity. It
      can be included in the glycosyl hydrolase family 16. Gene fusion expression in
      Bacillus subtilis DN1885 followed by preliminary characterization of the
      recombinant gene product indicates that betaglIIA has a pI of 3.8 to 4.0 and is
      active on both laminarin and curdlan, having an acid optimum pH activity (ca.
      4.0).

PMID- 8755915
TI  - Identification of two splicing mutations in the collagen type VII gene (COL7A1)
      of a patient affected by the localisata variant of recessive dystrophic
      epidermolysis bullosa.
AB  - Collagen type VII gene (COL7A1) has been demonstrated to be altered in several
      variants of dystrophic epidermolysis bullosa (DEB), with either recessive or
      dominant mode of inheritance. We have identified two mutations in a patient
      affected by a localisata variant of recessive DEB (L-RDEB), which is
      characterized by the less severe phenotype of the syndrome. These mutations are
      the first splicing mutations so far described for COL7A1 in DEB. One mutation is
      a paternally inherited A-->G transition at position -2 of the donor splicing site
      of intron 3, which results in three aberrant mRNAs, depending on the skipping of
      exon 3, the usage of a cryptic donor site inside exon 3, or the maintenance of
      intron 3. The second mutation is a maternally inherited G-->A transition at
      position -1 of the donor splicing site of intron 95, which induces the activation
      of a cryptic donor site 7 nt upstream the normal site and gives rise to a deleted
      mRNA, in addition to the normal one. All aberrant mRNAs show a shift of the
      reading frame, thus generating premature termination codons of translation.
      Allele-specific analysis of the transcripts has shown that the maternal mutation
      does not completely abolish the correct splicing of COLVII pre-mRNA, thus
      allowing, in the patient, the synthesis of a certain level of a functional
      protein. This result is compatible with the mild clinical L-RDEB phenotype
      observed in our patient.

PMID- 8755916
TI  - Cost comparison of molecular versus conventional screening of relatives at risk
      for retinoblastoma.
AB  - To compare costs of molecular and conventional screening of retinoblastoma
      relatives, we evaluated the direct health care costs. With variables set at the
      most likely values (baseline), the expected cost (in 1994 Canadian dollars) of
      conventional screening was $31,430 for a prototype family consisting of seven at
      risk relatives (three clinic exams and eight examinations under anaesthetic over
      the first 3 years of life for each relative). For the molecular strategy that
      involves looking for the RB1 gene mutation in the proband, testing the relatives
      for that mutation, and clinical follow-up similar to conventional strategy for
      relatives with mutation, the expected cost was $8,674, using baseline variables.
      Sensitivity analysis over the range of values for each variable revealed a
      significant saving of health care dollars by the molecular route, indicating the
      benefit of redirecting economic resources to molecular diagnosis in
      retinoblastoma.

PMID- 8755917
TI  - Exhaustive mutation scanning by fluorescence-assisted mismatch analysis discloses
      new genotype-phenotype correlations in angiodema.
AB  - A complete mutational scan of the gene coding for the serpin C1 inhibitor,
      comprising all eight exons and adjacent intron sequences and 550 bp preceding the
      transcription start site, was rapidly accomplished in 36 unrelated angioedema
      patients by using fluorescence-assisted mismatch analysis (FAMA). Mutations
      accounting for C1 inhibitor deficiency were identified in every one of 34
      patients, with two failures turning out to be spurious cases. Two new
      substitution dimorphisms were also detected in introns. Changes affecting the C1
      inhibitor protein, distributed throughout the seven coding exons, provide new
      insights into the molecular pathology of serpins. Six different splice-site and
      two promoter mutations were also found. Among the latter, a C-->T transition
      within one of two putative CAAT boxes of this TATA-less promoter, the sole
      idiomorphic nucleotide change in this kindred, was found homozygous in the
      proband, at variance with the dominant mode of transmission observed for
      structural mutations. FAMA, in the chemical probes configuration used in this
      study, is a rapid and robust mutation-scanning procedure, applicable to large DNA
      segments or transcripts and proved capable of 100% detection. Moreover, it
      provides accurate positional information--and hence recognition of multiple
      substitutions, precise relationship with those already known, and often immediate
      identification of the nucleotide change.

PMID- 8755918
TI  - Mutations associated with variant phenotypes in ataxia-telangiectasia.
AB  - We have identified 14 families with ataxia-telangiectasia (A-T) in which mutation
      of the ATM gene is associated with a less severe clinical and cellular phenotype
      (approximately 10%-15% of A-T families identified in the United Kingdom). In 10
      of these families, all the homozygotes have a 137-bp insertion in their cDNA
      caused by a point mutation in a sequence resembling a splice-donor site. The
      second A-T allele has a different mutation in each patient. We show that the less
      severe phenotype in these patients is caused by some degree of normal splicing,
      which occurs as an alternative product from the insertion-containing allele. The
      level of the 137-bp PCR product containing the insertion was lowest in two
      patients who showed a later onset of cerebellar ataxia. A further four families
      who do not have this insertion have been identified. Mutations detected in two of
      four of these are missense mutations, normally rare in A-T patients. The
      demonstration of mutations giving rise to a slightly milder phenotype in A-T
      raises the interesting question of what range of phenotypes might occur in
      individuals in whom both mutations are milder. One possibility might be that
      individuals who are compound heterozygotes for ATM mutations are more common than
      we realize.

PMID- 8755919
TI  - Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines
      severity of disease.
AB  - The gene predisposing to neurofibromatosis type 2 (NF2) on human chromosome 22
      has revealed a wide variety of different mutations in NF2 individuals. These
      patients display a marked variability in clinical presentation, ranging from very
      severe disease with numerous tumors at a young age to a relatively mild condition
      much later in life. To investigate whether this phenotypic heterogeneity is
      determined by the type of mutation in NF2, we have collected clinical information
      on 111 NF2 cases from 73 different families on whom we have performed mutation
      screening in this gene. Sixty-seven individuals (56.2%) from 41 of these kindreds
      revealed 36 different putative disease-causing mutations. These include 26
      proposed protein-truncating alterations (frameshift deletions/insertions and
      nonsense mutations), 6 splice-site mutations, 2 missense mutations, 1 base
      substitution in the 3' UTR of the NF2 cDNA, and a single 3-bp in-frame insertion.
      Seventeen of these mutations are novel, whereas the remaining 19 have been
      described previously in other NF2 individuals or sporadic tumors. When
      individuals harboring protein-truncating mutations are compared with cases with
      single codon alterations, a significant correlation (P < .001) with clinical
      outcome is observed. Twenty-four of 28 patients with mutations that cause
      premature truncation of the NF2 protein, schwannomin, present with severe
      phenotypes. In contrast, all 16 cases from three families with mutations that
      affect only a single amino acid have mild NF2. These data provide conclusive
      evidence that a phenotype/genotype correlation exists for certain NF2 mutations.

PMID- 8755920
TI  - Molecular basis for secretor type alpha(1,2)-fucosyltransferase gene deficiency
      in a Japanese population: a fusion gene generated by unequal crossover
      responsible for the enzyme deficiency.
AB  - About 20%-25% of Caucasian individuals are nonsecretors who fail to express
      soluble A, B, H, and Lewis b histo-blood group antigens in secretory organs and
      secretory fluids because of the absence of the Secretor gene (FUT2)-encoded
      alpha(1,2)-fucosyltransferase (Se enzyme) activity. Recently, the FUT2 and a
      pseudogene have been isolated, and an Se enzyme-deficient allele (se) caused by a
      nonsense mutation (G428A, se1) in Caucasians has also been reported. Although we
      were unable to find the se1 allele, we have found a missense mutation (A385T,
      se2) and two nonsense mutations (C571T, se3 and C628T, se4) in the Japanese Se
      enzyme-deficient alleles. In addition, we have found a fusion gene, which
      consisted of the 5'-region of the pseudogene and the 3'-region of the functional
      FUT2, as a Se enzyme-deficient allele (se5). The DNA sequence analysis of the
      fusion gene indicated that the crossover region corresponded to regions between
      bases 253 and 313 of the pseudogene and between bases 211 and 271 of the FUT2.
      This finding suggested that the fusion gene was generated by homologous but
      unequal crossover. A population study on 141 randomly selected Japanese has
      indicated that the se2 is a common Se enzyme-deficient allele in the Japanese
      population. The results suggest that Se enzyme-deficient alleles are race
      specific.

PMID- 8755921
TI  - Molecular basis and haplotyping of the alphaII domain polymorphisms of spectrin:
      application to the study of hereditary elliptocytosis and pyropoikilocytosis.
AB  - Hereditary elliptocytosis (HE) and hereditary pyropoikilocytosis (HPP) are
      inherited disorders of erythrocyte shape that are frequently associated with
      abnormalities in alpha-spectrin, one of the principal structural proteins of the
      erythrocyte membrane skeleton. Five polymorphisms of the alpha-spectrin gene,
      located in a 6-kb interval of genomic DNA, were identified and analyzed in normal
      and mutant alpha-spectrin alleles. Three of these polymorphisms are due to single
      nucleotide substitutions in the alpha-spectrin gene coding region that lead to
      changes in the amino acid sequence. In combination, these three polymorphisms are
      responsible for the different peptide phenotypes of the alphaII domain previously
      observed following limited tryptic digestion of spectrin protein. The most common
      haplotype, type 1, was found predominantly in Caucasians and was the only
      haplotype identified in Asians. Haplotypes 2, 3, and 4 were identified
      predominantly in individuals of African ancestry and were commonly found in
      patients with HE or HPP. Analysis of coinheritance of alphaII domain
      polymorphisms with alpha-spectrin gene mutations causing HE or HPP in African
      American patients with HE and HPP suggests that, with one exception, a given
      HE/HPP mutation is present in an alpha-spectrin gene of only one haplotype,
      indicating a founder effect. The other two polymorphisms located in this region
      of the alpha-spectrin gene do not change the amino acid sequence of the encoded
      alpha-spectrin chain and are not in linkage disequilibrium with three of the four
      alphaII domain haplotypes. A model is proposed for the evolutionary origin of the
      different haplotypes.

PMID- 8755922
TI  - Mutation rate in the hypervariable VNTR g3 (D7S22) is affected by allele length
      and a flanking DNA sequence polymorphism near the repeat array.
AB  - The hypervariable human minisatellite locus D7S22 (g3) is highly polymorphic. The
      allelic distribution in D7S22 features a size clustering of the alleles and a
      comparably low allelic diversity among small alleles. This reduced diversity
      could reflect a situation where some alleles are less likely to mutate than
      others. Several factors could explain such an effect, including allele size,
      variation in repeat composition, and allelic differences in nearby cis-acting
      elements affecting the mutation rate. We have characterized 40 de novo mutations
      found on Southern blots in a large amount of paternity-testing material. There is
      a significant excess of paternal mutations, and small size changes are most
      frequent. Mutation rate is affected by allele length, with highest rates in
      larger alleles. Alleles of the family groups with D7S22 mutations and 50 small
      alleles were analyzed by nucleotide sequencing. Two hundred thirty-six base pairs
      of the immediate flanking region upstream of the repeat array were PCR amplified
      and screened for point mutations by DNA sequencing of the PCR products. Two base
      substitution polymorphisms were identified: one C/G transversion and one A/G
      transition, 54 bp and 173 bp upstream of the repeat array, respectively. There is
      a significant association between mutation and occurrence of 54C, while
      association is not obvious between mutation rate and the 173A/G variants. There
      is a marked association between different flanking haplotypes and allele size,
      and within the smallest allele-size group, all alleles had the 54G/173A
      haplotype. Both allele size and allelic state at site 54 remain associated with
      mutation rate when the other factor is controlled. Possible mechanisms behind the
      variation in mutation rate in D7S22 are discussed.

PMID- 8755923
TI  - The retrieval of ancient human DNA sequences.
AB  - DNA was extracted from approximately 600-year-old human remains found at an
      archaeological site in the southwestern United States, and mtDNA fragments were
      amplified by PCR. When these fragments were sequenced directly, multiple
      sequences seemed to be present. From three representative individuals, DNA
      fragments of different lengths were quantified and short overlapping
      amplification products cloned. When amplifications started from <40 molecules,
      clones contained several different sequences. In contrast, when they were
      initiated by a few thousand molecules, unambiguous and reproducible results were
      achieved. These results show that more experimental work than is often applied is
      necessary to ensure that DNA sequences amplified from ancient human remains are
      authentic. In particular, quantitation of the numbers of amplifiable molecules is
      a useful tool to determine the role of contaminating contemporary molecules and
      PCR errors in amplifications from ancient DNA.

PMID- 8755924
TI  - A locus for Fanconi anemia on 16q determined by homozygosity mapping.
AB  - We report the results of a genomewide scan using homozygosity mapping to identify
      genes causing Fanconi anemia, a genetically heterogeneous recessive disorder. By
      studying 23 inbred families, we detected linkage to a locus causing Fanconi
      anemia near marker D16S520 (16q24.3). Although -65% of our families displayed
      clear linkage to D16S520, we found strong evidence (P = .0013) of genetic
      heterogeneity. This result independently confirms the recent mapping of the FAA
      gene to chromosome 16 by Pronk et al. Family ascertainment was biased against a
      previously identified FAC gene on chromosome 9, and no linkage was observed to
      this locus. Simultaneous search analysis suggested several additional chromosomal
      regions that could account for a small fraction of Fanconi anemia in our
      families, but the sample size is insufficient to provide statistical
      significance. We also demonstrate the strong effect of marker allele frequencies
      on LOD scores obtained in homozygosity mapping and discuss ways to avoid false
      positives arising from this effect.

PMID- 8755925
TI  - An autosomal recessive nonsyndromic-hearing-loss locus identified by DNA pooling
      using two inbred Bedouin kindreds.
AB  - Autosomal recessive nonsyndromic hearing loss (ARNSHL) is the most common form of
      severe inherited childhood deafness. We present the linkage analysis of two
      inbred Bedouin kindreds from Israel that are affected with ARNSHL. A rapid
      genomewide screen for markers linked to the disease was performed by using pooled
      DNA samples. This screen revealed evidence for linkage with markers D9S922 and
      D9S301 on chromosome 9q. Genotyping of individuals from both kindreds confirmed
      linkage to chromosome 9q and a maximum combined LOD score of 26.2 (recombination
      fraction [theta] .025) with marker D9S927. The disease locus was mapped to a 1.6
      cM region of chromosome 9ql3-q2l, between markers D9S15 and D9S927. The disease
      segregates with a common haplotype in the two kindreds, at markers D9S927,
      D9S175, and D9S284 in the linked interval, supporting the hypothesis that both
      kindreds inherited the deafness gene from a common ancestor. Although this
      nonsyndromic-hearing-loss (NSHL) locus maps to the same cytogenetic interval as
      DFNB7, it does not overlap the currently defined DFNB7 interval and may represent
      (1) a novel form of NSHL in close proximity to DFNB7 or (2) a relocalization of
      the DFNB7 interval to a region telomeric to its reported location. This study
      further demonstrates that DNA pooling is an effective means of quickly
      identifying regions of linkage in inbred families with heterogeneous autosomal
      recessive disorders.

PMID- 8755926
TI  - Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4):
      clinical description and genetic localization to chromosome 16q22.1.
AB  - The hereditary ataxias represent a clinically and genetically heterogeneous group
      of neurodegenerative disorders. Various classification schemes based on clinical
      criteria are being replaced as molecular characterization of the ataxias
      proceeds; so far, seven distinct autosomal dominant hereditary ataxias have been
      genetically mapped in the human genome. We report linkage to chromosome 16q22.1
      for one of these genes (SCA4) in a five-generation family with an autosomal
      dominant, late-onset spinocerebellar ataxia; the gene is tightly linked to the
      microsatellite marker D16S397 (LOD score = 5.93 at theta = .00). In addition, we
      present clinical and electrophysiological data regarding the distinct and
      previously unreported phenotype consisting of ataxia with the invariant presence
      of a prominent axonal sensory neuropathy.

PMID- 8755927
TI  - Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain
      lesions.
AB  - Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by
      seizures, mental retardation, and hamartomatous lesions. Although hamartomas can
      occur in almost any organ, they are most common in the brain, kidney, heart, and
      skin. Allelic loss or loss of heterozygosity (LOH) in TSC lesions has previously
      been reported on chromosomes 16p13 and 9q34, the locations of the TSC2 and TSC1
      genes, respectively, suggesting that the TSC genes act as tumor-suppressor genes.
      In our study, 87 lesions from 47 TSC patients were analyzed for LOH in the TSC1
      and TSC2 chromosomal regions. Three findings resulted from this analysis. First,
      we confirmed that the TSC1 critical region is distal to D9S149. Second, we found
      LOH more frequently on chromosome 16p13 than on 9q34. Of the 28 patients with
      angiomyolipomas or rhabdomyomas, 16p13 LOH was detected in lesions from 12 (57%)
      of 21 informative patients, while 9q34 LOH was detected in lesions from only 1
      patient (4%). This could indicate that TSC2 tumors are more likely than TSC1
      tumors to require surgical resection or that TSC2 is more common than TSC1 in our
      patient population. It is also possible that small regions of 9q34 LOH were
      missed. Lastly, LOH was found in 56% of renal angiomyolipomas and cardiac
      rhabdomyormas but in only 4% of TSC brain lesions. This suggests that brain
      lesions can result from different pathogenic mechanisms than kidney and heart
      lesions.

PMID- 8755928
TI  - Large domains of apparent delayed replication timing associated with triplet
      repeat expansion at FRAXA and FRAXE.
AB  - Trinucleotide repeat expansions have been implicated in the causation of a number
      of neurodegenerative disorders. In the case of fragile X syndrome, full expansion
      of the FMR1 repeat element (CGG)n has also been correlated with replication
      timing delay of the locus and proximal flanking sequences in male lymphoblasts.
      To define more extensively this altered region of DNA replication, as well as to
      extend these studies to female cells containing premutant and mutant alleles,
      study of the replication timing properties of a >2-Mb zone in the FRAXA region
      (Xq27.3-q28) was undertaken by using a FISH technique. In this assay, relative
      times of replication of specific loci are inferred from the ratios of singlet and
      doublet hybridization signals in interphase nuclei. In all individuals with a
      full expansion of the trinucleotide repeat, a large (1-1.2-Mb) region of delayed
      timing was observed; the apparent timing of the earlier-replicating allele in
      female cells in this region was intermediate between normal and affected alleles
      in males, which is in accordance with expectations of a mixed population of cells
      resulting from random X inactivation. In addition, expansion of the nearby FRAXE
      locus also was found to correlate with replication timing delay, although the
      extent of the altered region was somewhat less. Trinucleotide repeat expansion
      thus may be acting in the Xq27.3-q28 region to alter long-range chromatin
      structure that could influence transcription of gene sequences within the
      affected domain.

PMID- 8755929
TI  - Molecular analysis of chromosome 9q deletions in two Gorlin syndrome patients.
AB  - Gorlin syndrome is an autosomal dominant disorder characterized by multiple basal
      cell carcinomas, medulloblastomas, ovarian fibromas, and a variety of
      developmental defects. All affected individuals share certain key features, but
      there is significant phenotypic variability within and among kindreds with
      respect to malformations. The gene (NBCCS) maps to chromosome 9q22, and allelic
      loss at this location is common in tumors from Gorlin syndrome patients. Two
      recessive cancer-predisposition syndromes, xeroderma pigmentosum group A (XPAC)
      and Fanconi anemia group C (FACC), map to the NBCCS region; and unusual, dominant
      mutations in these genes have been proposed as the cause of Gorlin syndrome. This
      study presents cytogenetic and molecular characterization of germ-line deletions
      in one patient with a chromosome 9q22 deletion and in a second patient with a
      deletion of 9q22-q3l. Both have typical features of Gorlin syndrome plus
      additional findings, including mental retardation, conductive hearing loss, and
      failure to thrive. That Gorlin syndrome can be caused by null mutations
      (deletions) rather than by activating mutations has several implications. First,
      in conjunction with previous analyses of allelic loss in tumors, this study
      provides evidence that associated neoplasms arise with homozygous inactivation of
      the gene. In addition, dominant mutations of the XPAC and FACC1 genes can be
      ruled out as the cause of Gorlin syndrome, since the two patients described have
      null mutations. Finally, phenotypic features that show variable expression must
      be influenced by genetic background, epigenetic effects, somatic mutations, or
      environmental factors, since these two patients with identical alterations
      (deletions) of the Gorlin syndrome gene have somewhat different manifestations of
      Gorlin syndrome.

PMID- 8755930
TI  - Allele-specific replication of 15q11-q13 loci: a diagnostic test for detection of
      uniparental disomy.
AB  - Allele-specific replication differences have been observed in imprinted
      chromosomal regions. We have exploited this characteristic of an imprinted region
      by using FISH at D15S9 and SNRPN (small nuclear ribonucleo protein N) on
      interphase nuclei to distinguish between Angelman and Prader-Willi syndrome
      patient samples with uniparental disomy of chromosome 15q11-q13 (n = 11) from
      those with biparental inheritance (n = 13). The familial recurrence risks are low
      when the child has de novo uniparental disomy and may be as high as 50% when the
      child has biparental inheritance. The frequency of interphase cells with
      asynchronous replication was significantly lower in patients with uniparental
      disomy than in patients with biparental inheritance. Within the sample population
      of patients with biparental inheritance, those with altered methylation and
      presumably imprinting center mutations could not be distinguished from those with
      no currently detectable mutation. This test is cost effective because it is
      performed on interphase cells from the same hybridized cytological preparation in
      which a deletion is excluded, and additional specimens are not required to
      determine the parental origin of chromosome 15.

PMID- 8755931
TI  - Complete paternal isodisomy for chromosome 8 unmasked by lipoprotein lipase
      deficiency.
AB  - Uniparental disomy (UPD)-the inheritance of two homologous chromosomes from a
      single parent-may be unmasked in humans by the unexpected appearance of
      developmental abnormalities, genetic disorders resulting from genomic imprinting,
      or recessive traits. Here we report a female patient with familial
      chylomicronemia resulting from complete lipoprotein-lipase (LPL) deficiency due
      to homozygosity for a frameshift mutation in exon 2 of the LPL gene. She was the
      normal term product of an unremarkable pregnancy and had shown normal development
      until her current age of 5.5 years. The father (age 33 years) and the mother (age
      24 years) were unrelated and healthy, with no family history of stillbirths or
      malformations. The father was a heterozygous carrier of the mutation, whereas no
      mutation in the LPL gene was detected in the mother. Southern blotting did not
      reveal any LPL gene rearrangement in the proband or her parents. The proband was
      homozygous for 17 informative markers spanning both arms of chromosome 8 and
      specifically for the haplotype containing the paternally derived LPL gene. This
      shows that homozygosity for the defective mutation in the LPL gene resulted from
      a complete paternal isodisomy for chromosome 8. This is the first report of UPD
      for chromosome 8 unmasked by LPL deficiency and suggests that normal development
      can occur with two paternally derived copies of human chromosome 8.

PMID- 8755933
TI  - Founder effect and prevalence of myotonic dystrophy in South Africans: molecular
      studies.
AB  - A high prevalence of myotonic dystrophy (DM) has been described in South African
      Caucasoid Afrikaans-speaking families in the northern Transvaal. Evidence is
      presented for a strong founder effect, with a single haplotype occurring on 68%
      of all Caucasoid DM chromosomes; among the Afrikaans speakers, the proportion was
      83%. In addition to this major haplotype, five minor DM haplotypes in the
      Caucasoids and two minor haplotypes in DM individuals of mixed ancestry were
      found. All DM chromosomes, however, had a common haplotype core, namely, Alu
      (ins), HinfI-2 (intron 9), and TaqI-2 (D19S463). We have detected significant
      linkage disequilibrium between the DM mutation and particular alleles of the
      extragenic markers D19S112 and D19S207. Significant differences were found in
      allele and haplotype distributions in the Caucasoid DM and non-DM chromosomes and
      Negroid non-DM chromosomes. These findings together with the strong association
      of allele 3 at the D19S63 locus on 93% (14/15) of the South African DM
      chromosomes suggest that the majority of present-day DM mutations in South
      African Caucasoids may have originated from a common initial founder who
      introduced one of the European ancestral mutations.

PMID- 8755932
TI  - mtDNA sequence diversity in Africa.
AB  - mtDNA sequences were determined from 241 individuals from nine ethnic groups in
      Africa. When they were compared with published data from other groups, it was
      found that the !Kung, Mbuti, and Biaka show on the order of 10 times more
      sequence differences between the three groups, as well as between those and the
      other groups (the Fulbe, Hausa, Tuareg, Songhai, Kanuri, Yoruba, Mandenka,
      Somali, Tukana, and Kikuyu), than these other groups do between one other.
      Furthermore, the pairwise sequence distributions, patterns of coalescence events,
      and numbers of variable positions relative to the mean sequence difference
      indicate that the former three groups have been of constant size over time,
      whereas the latter have expanded in size. We suggest that this reflects
      subsistence patterns in that the populations that have expanded in size are food
      producers whereas those that have not are hunters and gatherers.

PMID- 8755934
TI  - Segregation analysis indicates a major gene in the control of interleukine-5
      production in humans infected with Schistosoma mansoni.
AB  - The interleukine-5 (IL-5) is a hormone of the immune system that is the main
      regulator of eosinopoiesis, eosinophil maturation and activation, and
      immunoglobulin A production. Thus, IL-5 contributes in several ways to human
      immune defenses against various pathogens, including helminths and infectious
      agents of the digestive and respiratory tracts. On the other hand, the increase
      in eosinophil number and the activation of these cells, which both have been
      related to elevated IL-5 production, are the cause of severe pathological
      disorders, as in asthma or hypereosinophilic syndromes. Although the
      immunological pathways leading to IL-5 synthesis have been identified, the
      reasons for the large variability observed in IL-5 production among subjects
      exposed to comparable antigenic stimulation are unknown. To investigate the role
      of genetic factors in this variability, we conducted a segregation analysis in a
      Brazilian population infected by the helminth parasite Schistosoma mansoni. The
      analysis was performed on IL-5 levels produced by blood mononuclear cells of
      these subjects after in vitro restimulation with either parasite extracts (IL
      5/schistosomula sonicates [SS] phenotype) or a T-lymphocyte mitogen (IL
      5/phytohemagglutin [PHA]). The results provide clear evidence for the segregation
      of a codominant major gene controlling IL-5/SS and IL-5/PHA production and
      accounting for 70% and 73% of the phenotypic variance, respectively; the
      frequency of the allele predisposing to low IL-5 production was approximately .22
      for both phenotypes. No significant relationship was found between these genes
      and the gene controlling infection intensities by S. mansoni detected in a
      previous study. Linkage studies are ongoing to locate those genes that would help
      to characterize the genetic factors involved in pathological conditions such as
      severe helminth infections and allergic diseases.

PMID- 8755936
TI  - ASHG report. Statement on informed consent for genetic research. The American
      Society of Human Genetics.

PMID- 8755935
TI  - The immunoglobulin heavy-chain variable region in insulin-dependent diabetes
      mellitus: affected-sib-pair analysis and association studies.
AB  - We have analyzed immunoglobulin heavy-chain variable-region (VH) polymorphisms
      and genetic susceptibility to insulin-dependent diabetes mellitus (IDDM) by using
      a set of polymorphic loci that span approximately 1,000 kb of the VH region on
      chromosome 14q32. One hundred one Finnish families with at least two children
      affected with IDDM were studied. Conventional RFLPs determined by hybridization
      were used, since no microsatellite repeat markers have been available for this
      gene region. No evidence for linkage between the VH genes and IDDM could be
      obtained from haplotype-sharing analysis among the 133 diabetic sib pairs. The
      frequencies of various VH genotypes were also compared between 101 familial IDDM
      cases and 114 controls derived from the Finnish background population. The
      distribution of the genotypes at the VH2-B5 locus was significantly different
      between these groups (P=.004), the 3.4/3.4 genotype being less common in the IDDM
      cases. In addition, a different genotype distribution at the VH5-B2 locus was
      observed in the diabetic subjects (P = .022). When the IDDM cases were stratified
      by presence or absence of the high-risk HLA-DQB1*0302 allele, no differences in
      VH genotype frequencies were observed between the 0302-positive and 0302-negative
      cases. In the transmission test for linkage disequilibrium (TDT), no differences
      were found between the expected and observed frequencies of the transmitted
      alleles at the VH2-B5 or VH5-B2 locus. In conclusion, significant differences in
      VH genotype distributions were observed between the familial IDDM cases and the
      controls, but the observed associations could not be confirmed by the TDT.
      Haplotype sharing analysis provided no evidence for genetic linkage between the
      VH gene region and IDDM.

PMID- 8755937
TI  - Errors in Huntington disease diagnostic test caused by trinucleotide deletion in
      the IT15 gene.

PMID- 8755938
TI  - Submicroscopic deletions are rare in Alagille syndrome.

PMID- 8755939
TI  - The molecular basis of fragile sites.

PMID- 8755940
TI  - Segregation of two BRCA1 mutations in a single family.

PMID- 8755941
TI  - Primary pathogenic mtDNA mutations in multigeneration pedigrees with Leber
      hereditary optic neuropathy.

PMID- 8755942
TI  - Even a deficit of shared marker alleles in affected sib pairs can yield evidence
      for linkage.

PMID- 8755943
TI  - A common BRCA1 mutation in Norwegian breast and ovarian cancer families?

PMID- 8755944
TI  - The Bell Curve: statement by the NIH-DOE Joint Working Group on the Ethical,
      Legal, and Social Implications of Human Genome Research.

PMID- 8755945
TI  - Defects in RNA splicing and the consequence of shortened translational reading
      frames.

PMID- 8755946
TI  - Genetic tests: a search for economy of scale.

PMID- 8755947
TI  - Detection of unknown mutations in DNA: a catch-22.

PMID- 8755951
TI  - Reminder about organized reporting of adverse reactions.

PMID- 8755952
TI  - Steps to enhance the future of our profession.

PMID- 8755953
TI  - Thoughts on recent changes in the profession.

PMID- 8755954
TI  - Questions effectiveness of Spay Day.

PMID- 8755955
TI  - Interpretation of the principles of veterinary bioethics.

PMID- 8755957
TI  - Questions methods used to validate tympanic thermometry.

PMID- 8755958
TI  - Responses to letter about exposure to toxic chemicals.

PMID- 8755956
TI  - Favors trend in part-time work for mothers.

PMID- 8755959
TI  - Not sure TQM leads to medical excellence.

PMID- 8755961
TI  - Forum article on nonhuman animal research elicits considerable dialogue.

PMID- 8755960
TI  - In favor of shelf arthroplasty in some dogs.

PMID- 8755962
TI  - Forum article on nonhuman animal research elicits considerable dialogue.

PMID- 8755963
TI  - Forum article on nonhuman animal research elicits considerable dialogue.

PMID- 8755964
TI  - Forum article on nonhuman animal research elicits considerable dialogue.

PMID- 8755965
TI  - Forum article on nonhuman animal research elicits considerable dialogue.

PMID- 8755966
TI  - Forum article on nonhuman animal research elicits considerable dialogue.

PMID- 8755967
TI  - Forum article on nonhuman animal research elicits considerable dialogue.

PMID- 8755968
TI  - Forum article on nonhuman animal research elicits considerable dialogue.

PMID- 8755969
TI  - History of veterinary service with the cavalry in the US Army.

PMID- 8755970
TI  - Salmonellosis in horses.

PMID- 8755971
TI  - What is your diagnosis? Portoazygos shunt and urinary calculi in a dog.

PMID- 8755972
TI  - What is your diagnosis? Infiltrative bowel disease with associated
      lymphadenopathy.

PMID- 8755973
TI  - Group decision making.

PMID- 8755974
TI  - Veterinary medical records--some legal issues.

PMID- 8755975
TI  - Risk factors for relinquishment of dogs to an animal shelter.
AB  - OBJECTIVE: To identify canine and household characteristics associated with
      relinquishment of a pet dog to an animal shelter. DESIGN: Case-control study.
      SAMPLE POPULATION: Households that relinquished dogs for adoption (case
      households) and a random sample of current dog-owning households in the same
      community (control households). RESULTS: Potentially modifiable factors that
      explained the highest proportion of relinquishment were owners not participating
      in dog obedience classes after acquisition, lack of veterinary care, owning a
      sexually intact dog, inappropriate care expectations, and dogs having daily or
      weekly inappropriate elimination. Dogs obtained from shelters, kept in crates, or
      acquired at > or = 6 months of age were at increased risk of relinquishment.
      Greater purchase price was associated with decreased risk of relinquishment, but
      relinquishment was not associated with the degree of planning to acquire the dog.
      Dogs with behavioral problems and little veterinary care were at greater risk of
      relinquishment than were dogs with regular veterinary care, and behavioral
      problems were associated with inappropriate care expectations. CLINICAL
      IMPLICATIONS: Risk factors identified in this study can be modified by dog owners
      and veterinarians to decrease the estimated 2 million dogs euthanatized annually
      in animal shelters. Veterinarians should educate owners about typical dog
      behavior, routine care requirements and training, and the importance of regular
      veterinary visits; should incorporate wellness concepts in their practice; and
      should focus on preventive medicine and behavioral consultation.

PMID- 8755976
TI  - Risk factors for relinquishment of cats to an animal shelter.
AB  - OBJECTIVE: To identify feline and household characteristics associated with
      relinquishment of a pet cat to an animal shelter. DESIGN: Case-control study.
      SAMPLE POPULATION: Households that relinquished cats for adoption (case
      households) and a random sample of current cat-owning households in the same
      community (control households). RESULTS: Potentially modifiable risk factors with
      the highest population attributable risk for relinquishment were owners having
      specific expectations about the cat's role in the household, allowing the cat
      outdoors, owning a sexually intact cat, never having read a book about cat
      behavior, cats having daily or weekly inappropriate elimination, and
      inappropriate care expectations. Frequency of inappropriate elimination and
      aggression toward people were not associated with declaw status, but these
      behaviors were more common among sexually intact cats, compared with sterilized
      cats. Owners of cats in case households were more likely than owners in control
      households to cite cost of sterilization as a reason a cat was sexually intact.
      Cats found as strays and cats acquired with minimal planning were at decreased
      risk of relinquishment. CLINICAL IMPLICATIONS: The identified risk factors can be
      modified by cat owners and veterinarians to decrease the estimated 4 million cats
      euthanatized annually in animal shelters. Owner education programs are needed as
      well as increased awareness on the part of cat owners and veterinarians of the
      importance of resolving feline inappropriate elimination problems.

PMID- 8755977
TI  - Patterns of chemical residues detected in US beef carcasses between 1991 and
      1993.
AB  - A study of data from 12 states in the Food Safety Inspection Service's Residue
      Violation Information System was conducted to describe patterns of violative
      chemical residues in US beef during 1991, 1992, and 1993. In 1991, 3,249
      violative residues were found in 2,734 carcasses in the 12 states included in the
      study. In 1992, 3,132 violative residues were found in 2,813 carcasses, and in
      1993, 2,317 violative residues were found in 2,051 carcasses. During each of the
      3 years, the Calf Antibiotic and Sulfonamide Test and Swab Test On Premises
      projects detected most of the violative residues, and producers/independent
      growers and dairy farms were recorded as the responsible sources for most of the
      violations. Also, most of the animals found to have violative residues were bob
      calves and culled cows. In bob calves, neomycin was the most frequently
      identified violative chemical, followed by tetracycline, gentamicin,
      oxytetracycline, and penicillin. In culled cows, penicillin was the most
      frequently identified violative chemical and was the chemical most frequently
      found in combination with other chemicals in cows with multiple violative
      residues. Distribution patterns of violative chemical residues by slaughter class
      and residue type varied among the 5 Food Safety Inspection Service regions. These
      specific regional characteristics support the need for customized intervention,
      education, assessment, and prevention programs.

PMID- 8755978
TI  - Epidural administration of bupivacaine, morphine, or their combination for
      postoperative analgesia in dogs.
AB  - OBJECTIVE: To compare the analgesic effects of epidural administration of
      morphine (MOR), bupivacaine hydrochloride (BUP), their combination (COM), and
      0.9% sterile NaCl solution (SAL) in dogs undergoing hind limb orthopedic
      surgeries. DESIGN: Blinded, randomized clinical trial. ANIMALS: 41 healthy dogs
      admitted for elective orthopedic surgeries involving the pelvis or hind limbs.
      PROCEDURE: Analgesic and control agents were administered postoperatively prior
      to recovery from isoflurane anesthesia. Ten dogs received MOR, 0.1 mg/kg of body
      weight; 10 received BUP, 0.5%, 1 ml/10-cm distance from the occipital
      protuberance to the lumbosacral space; 11 received COM; and 10 received SAL
      epidurally. Dogs were monitored for 24 hours after epidural injection for pain
      score, heart and respiratory rates, blood pressure, time to required
      administration of supplemental analgesic agent, total number of supplemental
      doses of analgesic agent required, and plasma concentrations of cortisol, MOR,
      and BUP. RESULTS: Pain scores were significantly lower in dogs in the COM and BUP
      groups than in dogs in the SAL group. Pain scores also were significantly lower
      in dogs in the COM group than in dogs in the MOR group. Time to required
      administration of supplemental analgesic agent was longer for dogs in the COM
      group than for dogs in the MOR and SAL groups. Total number of supplemental doses
      of analgesic agent required was lower for dogs in the BUP and COM groups than for
      dogs in the SAL group. CLINICAL IMPLICATIONS: Postoperative epidural
      administration of COM or BUP alone provides longer-lasting analgesia, compared
      with MOR or SAL.

PMID- 8755979
TI  - Responses of dogs with food allergies to single-ingredient dietary provocation.
AB  - OBJECTIVE: To characterize specific food ingredients causing allergic reactions
      in dogs and to assess cross-reactivity between proteins derived from a single
      animal source or from different plant products. DESIGN: Prospective study.
      ANIMALS: 25 dogs with histories and cutaneous signs consistent with food-allergic
      dermatitis. PROCEDURE: Dogs were fed a food-elimination diet until resolution of
      clinical signs and then challenged with their original diet. A diagnosis of food
      allergy was made if there was complete return of pruritus within 14 days of
      challenge exposure. After diagnosis, dogs were fed the food-elimination diet
      until signs related to dietary challenge abated. The dogs then were fed beef,
      chicken, chicken eggs, cows' milk, wheat, soy, and corn in single-ingredient
      provocation trials for 1 week. Any cutaneous reactions to these food ingredients
      were recorded by their owners. RESULTS: Beef and soy most often caused adverse
      cutaneous reactions, although all ingredients induced clinical signs in at least
      1 dog. Mean number of allergens per dog was 2.4, with 80% reacting to 1 or 2
      proteins and 64% reacting to 2 or more of the proteins tested. A significant
      difference was found between dogs reacting to beef versus cows' milk and between
      dogs reacting to soy versus wheat; thus, the hypothesis of cross-reactivity to
      ingredients derived from a single animal source or to different plant products
      was not supported. Similar differences between chicken meat and eggs were not
      identified. CLINICAL IMPLICATIONS: Long-term management of dogs with food
      allergies is facilitated by identification of the most commonly encountered food
      allergens. Because cross-reactivity cannot be verified, each protein source
      should be included separately in food-provocation trials.

PMID- 8755980
TI  - Liposarcoma associated with a glass foreign body in a dog.
AB  - An 11-year-old spayed female mixed-breed dog was referred for evaluation of a
      mass on the right forelimb of 4 months' duration. Cytologic examination of a fine
      needle aspirate of the mass resulted in a diagnosis of liposarcoma. The 3 x 3 x
      1.5-cm firm mass was surgically removed. Histopathologic observations confirmed
      the diagnosis of liposarcoma. During processing, a 1 x 0.8-cm piece of glass was
      found within the mass. Association between a glass foreign body and liposarcoma
      is discussed.

PMID- 8755981
TI  - Use of allopurinol to treat visceral leishmaniosis in a dog.
AB  - Visceral leishmaniosis was diagnosed in a working sled dog on the basis of
      history, clinical signs, and identification of amastigotes in a skin biopsy
      specimen. Allopurinol was administered as sole treatment for the disease. The
      drug was given for 9 months, and, during this time, clinical signs of disease
      resolved. Laboratory abnormalities had resolved by 12 months after diagnosis and
      3 months after treatment. The dog has been without medications for 19 months and
      remains free of clinical signs, has sired 2 litters, and functions well as lead
      sled dog for a team.

PMID- 8755982
TI  - Fulminant hepatic failure associated with oral administration of diazepam in 11
      cats.
AB  - Acute fulminant hepatic necrosis was associated with repeated oral administration
      of diazepam (1.25 to 2 mg, PO, q 24 or 12 h), prescribed for behavioral
      modification or to facilitate urination. Five of 11 cats became lethargic,
      atactic, and anorectic within 96 hours of initial treatment. All cats became
      jaundiced during the first 11 days of illness. Serum biochemical analysis
      revealed profoundly high alanine transaminase and aspartate transaminase
      activities. Results of coagulation tests in 3 cats revealed marked abnormalities.
      Ten cats died or were euthanatized within 15 days of initial drug administration,
      and only 1 cat survived. Histologic evaluation of hepatic tissue specimens from
      each cat revealed florid centrilobular hepatic necrosis, profound biliary ductule
      proliferation and hyperplasia, and suppurative intraductal inflammation.
      Idiosyncratic hepatotoxicosis was suspected because of the rarity of this
      condition. Prior sensitization to diazepam was possible in only 1 cat, and
      consistent risk factors that could explain susceptibility to drug toxicosis were
      not identified. On the basis of the presumption that diazepam was hepatotoxic in
      these cats, an increase in serum transaminase activity within 5 days of treatment
      initiation indicates a need to suspend drug administration and to provide
      supportive care.

PMID- 8755983
TI  - Analysis of spatial and temporal clustering of horses with Salmonella krefeld in
      an intensive care unit of a veterinary hospital.
AB  - OBJECTIVE: To determine whether clustering existed in the spatial or temporal
      distribution of horses that shed Salmonella krefeld in their feces during
      hospitalization. DESIGN: Retrospective analysis of medical records. ANIMALS: 219
      horses housed in the intensive care unit of a veterinary medical teaching
      hospital from October 1991 through May 1992. PROCEDURE: Bacteriologic culturing
      of fecal samples was used to identify horses shedding S krefeld. For affected
      horses, the scan statistic was used to analyze temporal clustering, and Knox's
      method was used to analyze temporal-spatial clustering. RESULTS: 20 horses were
      identified as shedding S krefeld in their feces. Significant temporal clustering
      of affected horses was observed for periods of 5, 6, 7, and 8 days. Temporal
      spatial analysis did not detect a significant distribution for any combination of
      time and distance among affected horses. CLINICAL IMPLICATIONS: Detection of
      temporal clustering and concurrent random temporal-spatial distribution of
      affected horses suggested that affected horses were grouped in time, but means of
      transmission was not related to proximity between horses.

PMID- 8755984
TI  - Control of an outbreak of salmonellosis caused by drug-resistant Salmonella
      anatum in horses at a veterinary hospital and measures to prevent future
      infections.
AB  - Salmonella anatum was isolated from horses treated at a private veterinary clinic
      or at a university veterinary medical teaching hospital. All isolates were
      resistant to most commonly used antibiotics. Because of the severity of disease
      resulting from outbreaks of infections with drug-resistant strains of S anatum,
      an epidemiologic investigation was conducted. Enteric bacteria, including S
      anatum, that were resistant to most antibiotics were isolated from the private
      veterinary clinic environment. Salmonella anatum was not isolated from the
      university teaching hospital environment. To prevent transmission, disinfection
      and isolation protocols were reviewed, and changes were implemented, including
      discontinuing use of power sprayers for cleaning, improving a two-step
      disinfection process, restricting movement of horses, and enhancing awareness of
      Salmonella spp transmission. Communication and prompt action are pivotal in
      preventing dissemination of resistant strains of Salmonella spp in a clinic or
      hospital environment.

PMID- 8755985
TI  - Intraosseous epidermoid cyst in a horse.
AB  - A 21-year-old female American Saddle Horse with a prominent swelling on the
      ventral aspect of the right hemimandible and radiographic evidence of a bone cyst
      was examined. The cyst cavity was surgically explored and was found to contain
      mucinous fluid and sheets of keratin. Microscopically, the cyst was lined by well
      differentiated squamous epithelium characterized by various degrees of
      hyperkeratosis and parakeratosis. The stromal component varied from scant areas
      in which epithelium was closely apposed to bone to wide regions of dense
      connective tissue that contained fragments of keratin surrounded by foreign-body
      giant cells. Histologic features were consistent with a diagnosis of intraosseous
      epidermoid cyst. After curettage of the cyst and repulsion of the second premolar
      tooth, drainage was established and iodine flushes were begun. Nine months after
      surgery, drainage was not detectable and size of the hemimandible had decreased
      by approximately a fourth.

PMID- 8755986
TI  - Tibial stress fractures in racing standardbreds: 13 cases (1989-1993).
AB  - OBJECTIVE: To determine clinical signs, radiographic and scintigraphic findings,
      and performance outcome of racing Standardbreds with tibial stress fractures.
      DESIGN: Retrospective case series. ANIMALS: 13 racing Standardbreds with tibial
      stress fractures. PROCEDURE: Information concerning clinical signs, diagnostic
      evaluation, and recommendations was obtained by review of the medical records.
      Performance information before and after diagnosis of the fracture was collected
      from racing records, and follow-up information was obtained from the owners or
      trainers by use of a telephone questionnaire. RESULTS: Horses with tibial stress
      fractures were moderately lame, and diagnosis was made by nuclear scintigraphy
      and radiography. Fractures were more likely to occur in 2-year-old horses than in
      older horses. The fracture location was unique for Standardbreds; 11 of 13
      developed stress fractures in the mid-diaphysis of the tibia, whereas fractures
      in Thoroughbreds are usually in the proximal caudal or caudolateral cortex.
      Fractures occurred in young horses that had raced or were in advanced race
      training. All horses were treated with rest alone, and 10 of 13 horses raced
      after injury. The horses that raced after injury were able to return to a level
      of performance that was equal to or better than the level raced before injury. 8
      of 10 horses established a lifetime-best winning time after injury. CLINICAL
      IMPLICATIONS: Tibial stress fractures are a cause of lameness in young racing
      Standardbreds. Diagnosis is aided by nuclear scintigraphy. The prognosis for
      return to previous level of performance after a tibial stress fracture is good.

PMID- 8755987
TI  - Alterations in blood lymphocyte subpopulations and hematologic values in neonatal
      calves after administration of a combination of multiple-antigen vaccines.
AB  - OBJECTIVE: To evaluate alterations in lymphocyte subpopulations, CBC results, and
      clinical signs in neonatal calves inoculated with 3 commercially available
      proprietary multiple-antigen vaccines containing known quantities of endotoxin.
      DESIGN: Prospective, randomized controlled field trial. ANIMALS: 36 healthy
      Holstein heifer calves between 3 and 31 days old. PROCEDURE: Vaccines were
      administered to 18 calves according to label instructions, except for the
      recommended age of administration. The 18 other calves served as unvaccinated
      controls. Two weeks after entry into the study, calves were given secondary doses
      of the same vaccines. Calves in both groups were examined and blood samples were
      collected for determination of lymphocyte subpopulations and hematological
      parameters once daily for 5 days beginning on the day that both the primary and
      the secondary vaccinations were given. Lymphocyte subpopulations, including
      BoCD2+, BoCD4+, BoCD8+, B cells, and gamma/delta T cells, were determined by use
      of flow cytometry, using monoclonal antibodies as markers. RESULTS: Vaccinated
      calves did not develop clinical signs of illness. There were no significant
      differences in absolute numbers of lymphocyte subpopulations between vaccinated
      and unvaccinated calves. Vaccinated calves had significantly higher rectal
      temperatures, total WBC counts, and absolute neutrophil counts than did control
      calves. These differences persisted for 3 to 4 days after vaccination. CLINICAL
      IMPLICATIONS: Findings confirm empirical observations that vaccination with
      multiple products at the same time may induce evidence of an inflammatory
      response in most calves. Additional research is indicated to further evaluate the
      safety of using multiple vaccines simultaneously.

PMID- 8755988
TI  - Commingled grazing as a risk factor for trichomonosis in beef herds.
AB  - OBJECTIVE: To evaluate commingled grazing on public lands as a risk factor for
      Tritrichomonas foetus infection in beef herd bulls. DESIGN: Case-control study.
      SAMPLE POPULATION: Based on 1994 data from the mandatory Idaho bull testing
      program, all 65 infected herds (case herds), 78 randomly selected test-negative
      herds that tested < 10 nonvirgin bulls, and 81 randomly selected test-negative
      herds that tested > or = 10 nonvirgin bulls (control herds). PROCEDURE: Managers
      of government-owned grazing lands in Idaho identified producers who had grazing
      permits for an allotment under their jurisdiction in 1993 and for that allotment
      recorded the number of animals the producer was permitted to graze on the
      allotment, the number of herds with grazing permits, the total number of animals
      permitted, and the dates on which grazing began and ended. The number of bulls
      tested, number of times tested, and test results were collated from the testing
      database. RESULTS: The relative sensitivity of bacterial culture of preputial
      smegma was 81%. The attributable fraction of T foetus infection associated with
      commingled grazing was 33%, and the odds ratio of infection was 9.0 for herds
      commingled with > or = 14 other herds. The total number of animals permitted on
      an allotment, the use of public lands, and type of public lands used were not
      significantly associated with infection status. CLINICAL IMPLICATIONS: These
      results suggest that to control the spread of trichomonosis, the number of herds
      commingling on a grazing allotment should be minimized and commingled herds
      should be managed collectively.

PMID- 8755989
TI  - Mycoplasma bovis-associated pneumonia and arthritis complicated with
      pyogranulomatous tenosynovitis in calves.
AB  - Immunohistochemistry and bacteriologic culturing were used to detect Mycoplasma
      bovis in tissue specimens from feedlot calves affected with pneumonia and
      arthritis. Two herds with 110 Charolais calves and 25 Angus calves were examined.
      Clinical signs included severe respiratory distress, anorexia, pyrexia, and
      lameness, which affected nearly a third of the calves. Lung lesions were
      characterized by numerous abscesses. Synovial lesions of the limbs included
      pyogranulomatous tenosynovitis, bursitis, and synovitis, particularly in the
      areas of the carpal and elbow joints. Abscesses in lung and synovial tissues
      contained accumulations of M bovis antigens, as revealed by immunohistochemistry.
      The findings of this report indicate that infection with M bovis may result in a
      pneumonia-arthritis syndrome with pyogranulomatous lesions in calves.

PMID- 8755990
TI  - Erection failure as a sequela to obstructive urolithiasis in a male goat.
AB  - A 14-month-old 40-kg Anglo-Nubian buck was referred for erection failure after
      recurrent bouts of obstructive urolithiasis. Previous episodes of obstructive
      urolithiasis were treated successfully with amputation of the urethral process,
      followed by an exploratory celiotomy and insertion of an indwelling Foley
      catheter into the bladder. The buck had been capable of intromission prior to the
      most recent episode of urethral obstruction. The results of physical examination
      and electroejaculation did not reveal any abnormalities, except failure to
      achieve erection. Contrast radiography of the corpus cavernosum penis (CCP),
      however, revealed failure of contrast media to migrate proximal to the sigmoid
      flexure. A diagnosis of obstruction of the CCP caused by cavernositis and
      fibrosis secondary to urolithiasis was made. A poor prognosis was given for
      breeding soundness. Although breeding soundness following obstructive
      urolithiasis may be enhanced by surgical intervention, impotence may result from
      obstruction of blood flow through the CCP secondary to urethral rupture or
      urethritis.

PMID- 8755991
TI  - Protein kinase C isoform expression in normal and failing rabbit hearts.
AB  - Protein kinase C (PKC) is activated by alpha-adrenergic stimulation. Molecular
      analysis showed that PKC consists of a family of at least 12 isozymes. Studies of
      their distribution in the heart showed conflicting results. The first goal of our
      study was thus to characterize cardiac PKC in normal rabbits. PKC plays an
      important role in gene expression, cell growth, and differentiation and is
      involved in the hypertrophy phase of cardiac overload, but since its expression
      has never been evaluated in heart failure, the second goal of our study was to
      evaluate PKC activity and isoform expression in rabbits with heart failure
      induced by a double hemodynamic overload (aortic insufficiency followed by an
      aortic stenosis). In the first part of the study, PKC isoform expression analyzed
      in normal rabbits by immunoblotting showed that isoforms alpha, beta, epsilon,
      and zeta were expressed along with PKC gamma, which had never been detected in
      the heart. PKC gamma expression was also identified by polymerase chain reaction,
      and immunofluorescence techniques showed a localization on intercalated disks
      associated with the membrane localization observed with the other isoforms. In
      the second part of the study, PKC activity, content, and isoform expression
      showed a decrease of 37% in the failing group. PKC immunodetection with a
      monoclonal antibody (Mab 1.9) recognizing the catalytic domain of all PKC
      isoforms revealed a 20% decrease in the failing ventricles compared with normal
      left ventricles. Expressed PKC isoforms quantified by Western blot showed, in the
      failing heart group compared with the control group, a decrease of 27%, 32%, 16%,
      and 9% of PKC alpha, PKC beta 1, PKC gamma, and PKC epsilon, respectively,
      whereas PKC zeta was not significantly modified. These results show that, in
      heart failure, PKC activity and expression of Ca(2+)-dependent PKC isoforms are
      decreased. This may lead to alterations of PKC-induced phosphorylations.

PMID- 8755992
TI  - Stimulation of the stress-activated mitogen-activated protein kinase subfamilies
      in perfused heart. p38/RK mitogen-activated protein kinases and c-Jun N-terminal
      kinases are activated by ischemia/reperfusion.
AB  - It has recently been recognized that cellular stresses activate certain members
      of the mitogen-activated protein kinase (MAPK) superfamily. One role of these
      "stress-activated" MAPKs is to increase the transactivating activity of the
      transcription factors c-Jun, Elk1, and ATF2. These findings may be particularly
      relevant to hearts that have been exposed to pathological stresses. Using the
      isolated perfused rat heart, we show that global ischemia does not activate the
      42- and 44-kD extracellular signal-regulated (protein) kinase (ERK) subfamily of
      MAPKs but rather stimulates a 38-kD activator of MAPK-activated protein kinase-2
      (MAPKAPK2). This activation is maintained during reperfusion. The molecular
      characteristics of this protein kinase suggest that it is a member of the
      p38/reactivating kinase (RK) group of stress-activated MAPKs. In contrast, stress
      activated MAPKs of the c-Jun N-terminal kinase (JNK/SAPKs) subfamily are not
      activated by ischemia alone but are activated by reperfusion following ischemia.
      Furthermore, transfection of ventricular myocytes with activated protein kinases
      (MEKK1 and SEK1) that may be involved in the upstream activation of JNK/ SAPKs
      induces increases in myocyte size and transcriptional changes typical of the
      hypertrophic response. We speculate that activation of multiple parallel MAPK
      pathways may be important in the responses of hearts to cellular stresses.

PMID- 8755993
TI  - Functional and structural assessment of intercellular communication. Increased
      conduction velocity and enhanced connexin expression in dibutyryl cAMP-treated
      cultured cardiac myocytes.
AB  - Remodeling of conduction pathways in the hypertrophic response to myocardial
      injury is a potential mechanism leading to the development of anatomic substrates
      of lethal arrhythmias. To delineate the responsible mechanisms and to directly
      relate changes in intercellular coupling at gap junctions with
      electrophysiological alterations, we studied the effects of cAMP, a mediator of
      cardiac hypertrophy, on action potential conduction velocity and connexin
      expression in neonatal rat ventricular myocyte cultures. Conduction velocity was
      measured with an optical activation mapping technique in cells loaded with the
      voltage-sensitive dye RH-237. Action potentials were conducted 24% to 29% more
      rapidly (P < .005) after incubating cultures for 24 hours with the cAMP analogue
      dibutyryl cAMP (db-cAMP, 1 mmol/L). However, db-cAMP caused no change in the
      maximum rate of rise of the action potential upstroke, Vmax. Electron and
      immunofluorescence microscopy revealed a significant increase in the number and
      size of gap junctions in db-cAMP-treated cells. Immunoblotting showed that the
      total amounts of the ventricular gap junction proteins connexin43 and connexin45
      (Cx43 and Cx45, respectively) increased 2- to 4-fold. Immuno-precipitation of
      metabolically labeled connexin proteins revealed a dose-dependent increase in the
      rate of Cx45 protein synthesis in myocytes exposed to db-cAMP ( > 2-fold after a
      4-hour exposure) but no change in the Cx43 synthesis rate. Northern blot analysis
      demonstrated a time-dependent increase in the amount of Cx43 mRNA, with a maximum
      3.3-fold increase after 4 hours of exposure to 1 mmol/L db-cAMP; cycloheximide
      did not block this effect. In contrast, Cx45 mRNA levels were not altered
      significantly after db-cAMP treatment. Thus, cAMP causes a significant increase
      in conduction velocity that appears to be attributable largely to enhanced
      expression of proteins responsible for intercellular communication. Cx43 and Cx45
      levels appear to be upregulated by cAMP by disparate molecular mechanisms.

PMID- 8755994
TI  - Alpha 1-adrenergic activation inhibits beta-adrenergic-stimulated unitary Ca2+
      currents in cardiac ventricular myocytes.
AB  - We have previously shown that whole-cell L-type Ca2+ current that was stimulated
      through beta-adrenergic receptors was negatively modulated by alpha 1-adrenergic
      activation. In the present study, we investigated the kinetic basis of this
      modulation at the single-channel level in adult rat ventricular myocytes using
      Ba2+ as the charge carrier. Unitary current sweeps were evoked by 300-ms
      depolarizing pulses to 0 mV, from a holding potential of -50 mV at 0.5 Hz. During
      control conditions, the ensemble-averaged current amplitude was 0.18 +/- 0.01 pA
      (n = 7). To achieve beta-adrenergic stimulation (beta effect), cells were
      superfused with norepinephrine (10 mumol/L) in the presence of prazosin (10
      mumol/L), an alpha 1-adrenergic blocker. beta-adrenergic stimulation enhanced
      ensemble-averaged current (from 0.18 +/- 0.01 to 0.75 +/- 0.04 pA, P < .05, n =
      7), increased the open-time constants, and decreased the closed-time constants.
      To activate alpha 1-receptors while maintaining the beta-adrenergic stimulation,
      cells were superfused with norepinephrine alone (alpha 1 + beta effects). alpha 1
      adrenergic activation reduced ensemble-averaged current (from 0.75 +/- 0.04 to
      0.41 +/- 0.03 pA, P < .05, n = 7), decreased open-time constants, and increased
      closed-time constants. alpha 1-adrenergic activation also inhibited ensemble
      averaged currents stimulated by a low concentration (10 mumol/L) of 8-bromo-cAMP
      but not by (-)Bay K 8644 (1 mumol/L). Calphostin C (1 mumol/L), a specific
      inhibitor of protein kinase C, attenuated alpha 1-adrenergic inhibition on beta
      adrenergic-stimulated unitary currents. We conclude that alpha 1-adrenergic
      activation exerts an inhibitory effect on beta-adrenergic-stimulated unitary Ba2+
      current at the single-channel level. The shortening of the open-time and the
      lengthening of the closed-time constants and the increase in blank sweeps may
      explain the inhibition of the Ca(2+)-channel activity and the reduction in whole
      cell Ca2+ current previously reported. This inhibition is in part mediated
      through the protein kinase C pathway.

PMID- 8755995
TI  - Ca2+ influx during the cardiac action potential in guinea pig ventricular
      myocytes.
AB  - The relative contributions of L-type Ca2+ current (ICa) and Na+/Ca2+ exchange to
      Ca2+ influx during the cardiac action potential (AP) are unknown. In this study,
      we have used an AP recorded under physiological conditions as the command voltage
      applied to voltage-clamped ventricular myocytes. ICa (measured as nifedipine
      sensitive membrane current) had a complex multiphasic time course during the AP.
      Peak ICa was typically 4 pA/pF, after which it rapidly declined (to about 60% of
      peak) during the rising phase of the cell-wide Ca2+ transient before increasing
      to a second, more sustained component. The initial decline in ICa was sensitive
      to the amount of Ca2+ released by the sarcoplasmic reticulum (SR), and conditions
      that reduce the amplitude of the Ca2+ transient (such as rest or brief
      application of caffeine) increased net Ca2+ influx via ICa. Dissection of the
      Na+/Ca2+ exchange current at the start of the AP suggested that Ca2+ influx via
      Na+/Ca2+ exchange is less than 30% of that due to ICa. From these data, we
      suggest that ICa is the primary source of Ca2+ that triggers SR Ca2+ release,
      even at the highly depolarized membrane potentials associated with the AP.
      However, Ca2+ influx via Na+/Ca2+ exchange is not negligible and may activate
      some Ca2+ release from the SR, especially when ICa is reduced. We propose that SR
      Ca2+ release inhibits ICa within the same beat, thereby providing a negative
      feedback mechanism that may serve to limit Ca2+ influx as well as to regulate the
      amount of Ca2+ stored within the SR.

PMID- 8755996
TI  - Distribution of cAMP-activated chloride current and CFTR mRNA in the guinea pig
      heart.
AB  - Guinea pig ventricular myocytes exhibit a Cl(-)-selective current regulated by
      the cAMP-dependent pathway. We have investigated the distribution of cAMP
      activated Cl- channel current density and cystic fibrosis transmembrane
      conductance regulator (CFTR) mRNA in three regions of the guinea pig heart: the
      atrium, and the epicardium and endocardium of the free wall of the left
      ventricle. The regional differences in the Cl- current density were investigated
      in enzymatically isolated myocytes using the whole-cell patch-clamp technique.
      Forskolin (1 mumol/L) activated Cl(-)-selective currents in all ventricular
      myocytes and 21% of atrial myocytes examined. The conductance density, estimated
      as the outward chord conductance normalized to cell capacitance, was greatest in
      epicardial myocytes (79.8 +/- 8.4 pS/pF, n = 21) and significantly lower in
      endocardial (59.8 +/- 9.5 pS/pF, n = 22) and atrial (10.9 +/- 5.0 pS/pF, n = 38)
      myocytes. The regional differences in CFTR mRNA expression levels were
      investigated by competitive reverse-transcribed polymerase chain reaction. The
      regional distribution of the mRNA levels was similar to that of the Cl-
      conductance density, ie, highest in the epicardium (23230 +/- 1840
      molecules/microgram total RNA, n = 3), significantly lower in endocardium (10610
      +/- 780 molecules/microgram total RNA, n = 3), and lowest in atrium (1450 +/- 290
      molecules/microgram total RNA, n = 3). The data indicate that regional
      differences in CFTR mRNA expression in the guinea pig heart are responsible, at
      least in part, for the regional differences in cAMP-activated Cl- current
      density.

PMID- 8755997
TI  - Simulation of action potentials from metabolically impaired cardiac myocytes.
      Role of ATP-sensitive K+ current.
AB  - The role of the ATP-sensitive K+ current (IK-ATP) and its contribution to
      electrophysiological changes that occur during metabolic impairment in cardiac
      ventricular myocytes is still being discussed. The aim of this work was to
      quantitatively study this issue by using computer modeling. A model of IK-ATP is
      formulated and incorporated into the Luo-Rudy ionic model of the ventricular
      action potential. Action potentials under different degrees of activation of IK
      ATP are simulated. Our results show that in normal ionic concentrations, only
      approximately 0.6% of the KATP channels, when open, should account for a 50%
      reduction in action potential duration. However, increased levels of
      intracellular Mg2+ counteract this shortening. Under conditions of high [K+]0,
      such as those found in early ischemia, the activation of only approximately 0.4%
      of the KATP channels could account for a 50% reduction in action potential
      duration. Thus, our results suggest that opening of IK-ATP channels should play a
      significant role in action potential shortening during hypoxic/ischemic episodes,
      with the fraction of open channels involved being very low ( < 1%). However, the
      results of the model suggest that activation of IK-ATP alone does not
      quantitatively account for the observed K+ efflux in metabolically impaired
      cardiac myocytes. Mechanisms other than KATP channel activation should be
      responsible for a significant part of the K+ efflux measured in hypoxic/ischemic
      situations.

PMID- 8755998
TI  - Maximal actomyosin ATPase activity and in vitro myosin motility are unaltered in
      human mitral regurgitation heart failure.
AB  - Myofibrillar but not actomyosin ATPase is depressed in failing myocardium from
      patients with dilated cardiomyopathy. Since there is a similar depression of
      myofibrillar ATPase in mitral regurgitation myocardium, we investigated whether
      or not the hydrolytic and mechanical performances of myosin are altered by
      comparing the maximal actomyosin ATPase activity and the in vitro myosin motility
      of myocardial myosin from patients with mitral regurgitation heart failure with
      that of patients with normal ventricular function. The results show that there is
      no significant difference (P > .05) between nonfailing and failing values for
      either the maximal actomyosin ATPase activity (0.3 s-1.head-1) or the myosin
      motility (1 micron/s). These observations suggest that changes, other than in the
      myosin heavy chain, contribute to the altered myocardial performance in mitral
      regurgitation myocardium.

PMID- 8755999
TI  - Exogenously administered growth hormone and insulin-like growth factor-I alter
      intracellular Ca2+ handling and enhance cardiac performance. In vitro evaluation
      in the isolated isovolumic buffer-perfused rat heart.
AB  - It has been proposed that chronic treatment with growth hormone (GH) or insulin
      like growth factor-I (IGF-I) in the rat may enhance cardiac function in vivo. To
      confirm these findings and elucidate the mechanisms by which cardiac function is
      modulated, we studied isolated buffer-perfused rat hearts after 4 weeks of
      treatment with high doses of GH and IGF-I alone or in combination. Mechanical
      parameters were measured at 50% of the intracardiac balloon volume at which
      maximal developed pressure (DevP) occurred. EC50 of the force-Ca2+ relationship
      and maximal Ca(2+)-activated systolic wall stress (max sigma s) were assessed by
      increasing Ca2+ in the perfusate in a stepwise fashion and plotting systolic wall
      stress (sigma s) versus intracellular peak systolic Ca2+, measured by the
      aequorin bioluminescence method. We found a marked increase of systolic pressure
      (Ps), DevP, and (+dP/dt)/DevP in the treated groups compared with the control
      group. The combination group showed a blunted effect. sigma s was increased in
      all treated groups for a perfusate Ca2+ concentration of > 1.5 mmol/L. The
      enhanced systolic performance can be explained by an increase of the overall Ca2+
      responsiveness due to an increased maximal response to Ca2+ even though the EC50
      of the Ca(2+)-dose response was also slightly increased. Ps was further enhanced
      by an increase of the relative wall thickness induced by the treatment. Diastolic
      pressure, diastolic Ca2+, and the amplitude and time course of the Ca2+ transient
      were not influenced by any treatment protocol. All treatments caused increases of
      body and heart weight. These data support the hypothesis that both IGF-I and GH
      directly affect cardiac performance by altering cardiac geometry as well as by
      enhancing max sigma s.

PMID- 8756001
TI  - In vivo assessment of embryonic cardiovascular dimensions and function in day
      10.5 to -14.5 mouse embryos.
AB  - Embryonic cardiovascular function has been extensively studied in vivo in the
      chick embryo. However, the geometry of mammalian and avian hearts differs; the
      mammalian cardiovascular system is coupled to both yolk sac and placental
      circulations, and unique murine genetic models associated with structural and
      functional cardiovascular defects are now available. We therefore adapted
      techniques validated for the chick embryo to define cardiovascular dimensions and
      function in the mouse embryo. We bred C3HeB female and C57B1/J6 male mice and ICR
      pairs for experiments on embryonic days (EDs) 10.5 to 14.5 (n = 130 dams). After
      maternal anesthesia (pentobarbital, 60 mg/kg IP), laparotomy, and sequential
      regional hysterotomy, we exposed and then imaged individual embryos at 60 Hz
      (video) in the ventral and/or left anterior oblique views while maintaining
      uteroplacental continuity. We measured epicardial chamber dimensions and then
      calculated right and left ventricular elliptical volumes from ares. In addition,
      we measured pulsed-Doppler blood velocity across the atrioventricular cushions
      and ventricular outflow tract. We maintained embryonic temperature with a heated
      surgical platform, topical oxygenated and warmed buffer, and warming lamps.
      Embryonic heart rate increased from 124.7 +/- 5.2 to 194.3 +/- 13.2 bpm from EDs
      10.5 to 14.5 (P < .01). Right and left ventricular end-diastolic and end-systolic
      dimensions increased (P < .05 by ANOVA for each). Maximal ventricular mean inflow
      and outflow velocities increased from 62.33 +/- 4.06 to 106.23 +/- 11.59 and from
      55.79 +/- 6.11 to 91.61 +/- 6.93 mm/s, respectively (P < .05 by ANOVA for each).
      Thus, as has been done for chick and rat embryos, the maturation of murine
      embryonic cardiovascular function can be quantified in vivo, setting the stage
      for the investigation of structure-function relations in mouse models of
      cardiovascular development and disease.

PMID- 8756000
TI  - Intracellular Ca2+, intercellular electrical coupling, and mechanical activity in
      ischemic rabbit papillary muscle. Effects of preconditioning and metabolic
      blockade.
AB  - During myocardial ischemia, electrical uncoupling and contracture herald
      irreversible damage. In the present study, we tested the hypothesis that an
      increase of intracellular Ca2+ is an important factor initiating these events.
      Therefore, we simultaneously determined tissue resistance, mechanical activity,
      pH(0), and intracellular Ca2+ (with the fluorescent indicator indo 1, Molecular
      Probes, Inc) in arterially perfused rabbit papillary muscles. Sustained ischemia
      was induced in three experimental groups: (1) control, (2) preparations
      preconditioned with two 5-minute periods of ischemia followed by reperfusion, and
      (3) preparations pretreated with 1 mmol/L iodoacetate to block anaerobic
      metabolism and minimize acidification during ischemia. In a fourth experimental
      group, intracellular Ca2+ was increased under nonischemic conditions by perfusing
      with 0.1 mmol/L ionomycin and 0.1 mumol/L gramicidin. Ca2+ transients and
      contractions rapidly disappeared after the induction of ischemia. In the control
      group, diastolic Ca2+ began to rise after 12.6 +/- 1.3 minutes of ischemia;
      uncoupling, after 14.5 +/- 1.2 minutes of ischemia; and contracture, after 12.6
      +/- 1.5 minutes of ischemia (mean +/- SEM). Preconditioning significantly
      postponed Ca2+ rise, uncoupling, and contracture (21.5 +/- 4.0, 24.0 +/- 4.1, and
      23.0 +/- 5.3 minutes of ischemia, respectively). Pretreatment with iodoacetate
      significantly advanced these events (1.9 +/- 0.7, 3.6 +/- 0.9, and 1.9 +/- 0.2
      minutes of ischemia, respectively). In all groups, the onset of uncoupling always
      followed the start of Ca2+ rise, whereas the start of contracture was not
      different from the rise in Ca2+. Perfusion with ionomycin and gramicidin
      permitted estimation of a threshold [Ca2+] for electrical uncoupling of 685 +/-
      85 nmol/L. In conclusion, the rise in intracellular Ca2+ is the main trigger for
      cellular uncoupling during ischemia. Contracture is closely associated with the
      increase of intracellular Ca2+ during ischemia.

PMID- 8756002
TI  - Hemodynamic effects of L- and D-S-nitrosocysteine in the rat. Stereoselective S
      nitrosothiol recognition sites.
AB  - The vasorelaxant effects of the endothelium-derived relaxing factor S
      nitrosocysteine (SNC) may not be simply due to its decomposition to NO. The
      biological actions of SNC may also involve the transnitrosation of amino acids in
      the blood and in plasma membranes. The possibility that the SNC moiety possesses
      biological activity prompted us to examine whether the hemodynamic effects of
      this S-nitrosothiol involves the activation of stereoselective S-nitrosothiol
      receptors within the cardiovascular system. We examined (1) the hemodynamic
      effects produced by intravenous injections of the L and D isomers of SNC (L- and
      D-SNC, respectively; 100 to 800 nmol/kg), the L and D isomers of the parent
      thiols (L- and D-cysteine, respectively; 100 to 800 nmol/kg), the oxidized thiol
      L-cystine (100 to 800 nmol/kg), and the NO donor sodium nitroprusside (SNP, 1 to
      36 micrograms/kg) in conscious freely moving rats, (2) the baroreceptor reflex
      mediated changes in heart rate elicited in response to the falls in arterial
      pressure produced by L- and D-SNC and SNP in conscious rats, and (3) the relative
      decomposition of L- and D-SNC to NO upon addition to heparinized rat blood or
      upon direct application to cultured porcine aortic smooth muscle (PASM) cells. We
      now report that (1) L-SNC is a more potent hypotensive and vasodilator agent
      within the mesenteric bed and sympathetically intact and sympathetically
      denervated hindlimb beds of conscious rats than is D-SNC, (2) L- and D-SNC
      markedly inhibit baroreceptor reflex-mediated tachycardia in conscious rats and D
      SNC is considerably more effective than L-SNC, (3) the intravenous injections of
      L- and D-cysteine or L-cystine do not affect arterial blood pressure or vascular
      resistances, and (4) L- and D-SNC decompose equally to NO upon application to rat
      blood or cultured PASM cells. These results suggest that the hemodynamic effects
      of endogenous SNC may involve its interaction with stereoselective S-nitrosothiol
      recognition sites within the vasculature and the baroreflex arc. These findings
      provide tentative evidence that membrane-bound S-nitrosothiol receptors may exist
      within the cardiovascular system.

PMID- 8756003
TI  - Heparin-binding epidermal growth factor-like growth factor regulates fibroblast
      growth factor-2 expression in aortic smooth muscle cells.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a vascular
      smooth muscle cell (SMC) mitogen and chemotactic factor that is expressed by
      endothelial cells, SMCs, monocytes/macrophages, and T lymphocytes. Both the
      membrane-anchored HB-EGF precursor and the secreted mature HB-EGF protein are
      biologically active; thus, HB-EGF may stimulate SMC growth via autocrine,
      paracrine, and juxtacrine mechanisms. In the present study, we report that HB-EGF
      treatment of serum-starved at aortic SMCs can induce fibroblast growth factor
      (FGF)-2 (basic FGF) gene expression but not FGF-1 (acidic FGF) gene expression.
      Increased FGF-2 mRNA expression is first detectable at 1 hour after HB-EGF
      addition, and maximal FGF-2 mRNA levels, corresponding to an approximately 46
      fold level of induction, are present at 4 hours. The effect of HB-EGF on FGF-2
      mRNA levels appears to be mediated primarily by a transcriptional mechanism and
      requires de novo synthesized proteins. HB-EGF induction of FGF-2 mRNA levels can
      be inhibited by treating cells with the anti-inflammatory glucocorticoid
      dexamethasone or the glycosaminoglycan heparin. Finally, Western blot analyses
      indicate that HB-EGF-treated SMCs also produce an increased amount of FGF-2
      protein. These results indicate that HB-EGF expressed at sites of vascular injury
      or inflammation in vivo may upregulate FGF-2 production by SMCs.

PMID- 8756004
TI  - Prostacyclin formation elicited by endothelin-1 in rat aorta is mediated via
      phospholipase D activation and not phospholipase C or A2.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor peptide that also stimulates
      production of prostacyclin (PGI2) from arachidonic acid. The purpose of this
      study was to determine the contribution of phospholipases (PLs) A2, C, and/or D
      in ET-1-induced PGI2 formation in the rat aorta, measured as immunoreactive 6
      ketoprostaglandin (PG) F1 alpha. ET-1 increased 6-keto-PGF1 alpha formation,
      which was not affected by a PLA2 inhibitor, 7,7-dimethyl eicosadienoic acid
      (DEDA). Furthermore, ET-1 failed to stimulate PLA2 activity measured in the
      cytosol (cPLA2), using phosphatidylcholine, L-a-1-palmitoyl-2-arachidonyl[14C] as
      a substrate. However, the adrenergic agonist norepinephrine increased 6-keto-PGF1
      alpha formation, which was attenuated by DEDA, and enhanced PLA2 activity. ET-1
      enhanced PLC activity, as indicated by increased inositol phosphate production,
      which was prevented by a PLC inhibitor, U-73122. However, ET-1-induced 6-keto
      PGF1 alpha production was not altered by U-73122. An inhibitor of PLD activation,
      C2-ceramide, attenuated ET-1-induced PLD activity, as indicated by the production
      of phosphatidylethanol. Furthermore, ET-1-induced 6-keto-PGF1 alpha formation was
      inhibited by C2-ceramide as well as by ethanol treatment. Moreover, inhibitors of
      phosphatidate phosphohydrolase (propranolol) and diacylglycerol lipase (RHC
      80267), attenuated ET-1-induced 6-keto-PGF1 alpha formation. Finally, ET-1
      induced activation of PLD was not attenuated by a selective PKC inhibitor,
      bisindolylmaleimide I. These data suggest a novel pathway for ET-1-induced PGI2
      formation in the rat aorta involving activation of PLD but not cPLA2 and
      independent of PLC or PKC activation.

PMID- 8756005
TI  - Characterization of the endothelium-specific murine vascular endothelial growth
      factor receptor-2 (Flk-1) promoter.
AB  - Flk-1, a high-affinity signaling receptor for vascular endothelial growth factor
      (VEGF), is strongly and specifically expressed on endothelial cells during
      embryonic development of the vascular system and during tumor angiogenesis.
      Disruption of Flk-1 gene function has recently been shown to prevent completely
      endothelial cell differentiation during murine embryonic development. To gain
      insights into the mechanisms that regulate the endothelium-specific Flk-1
      expression, we have isolated the 5'-flanking region of the murine Flk-1 gene.
      RNase protection and primer extension analyses revealed a single transcriptional
      start site located 299 bp upstream from the translational start site in an
      initiator-like pyrimidine-rich sequence. The 5'-flanking region is rich in GC
      residues and lacks a typical TATA or CAAT box. A luciferase reporter construct
      containing a fragment from nucleotides -1900 to +299 showed strong endothelium
      specific activity in transfected bovine aortic endothelial cells. Deletion
      analyses revealed that endothelium-specific Flk-1 expression is stimulated by the
      5'-untranslated region of the first exon, which contains an activating element
      between nucleotides +137 and +299. In addition, two endothelium-specific negative
      regulatory elements were identified between nucleotides -4100 and -623. Two
      strong general activating elements were present in the region between nucleotides
      -96 and -37, which contains one potential NF kappa B and three potential AP-2
      binding sites. This study shows that Flk-1 expression in endothelial cells is
      mainly regulated by an endothelium-specific activating element in the long 5'
      untranslated region of the first exon and by negative regulatory elements located
      further upstream.

PMID- 8756006
TI  - Thrombin potently stimulates cytokine production in human vascular smooth muscle
      cells but not in mononuclear phagocytes.
AB  - Thrombosis frequently occurs during atherogenesis and in response to vascular
      injury. Accumulating evidence supports a role for inflammation in the same
      situation. The present study therefore sought links between thrombosis and
      inflammation by determining whether thrombin, which is present in active form at
      sites of thrombosis, can elicit inflammatory functions of human monocytes and
      vascular smooth muscle cells (SMCs), two major constituents of advanced atheroma.
      Human alpha-thrombin (EC50, approximately equal to 500 pmol/L) potently induced
      interleukin (IL)-6 release from SMCs. The tethered-ligand thrombin receptor
      appeared to mediate this effect. Furthermore, alpha-thrombin also rapidly
      increased levels of mRNA encoding IL-6 and monocyte chemotactic protein-1 (MCP-1)
      in SMCs. In contrast, only alpha-thrombin concentrations of > or = 100 nmol/L
      could stimulate release of IL-6 or tumor necrosis factor-alpha (TNF alpha) in
      peripheral blood monocytes or monocyte-derived macrophages. Lipid loading of
      macrophages did not augment thrombin responsiveness. Likewise, only alpha
      thrombin concentrations of > or = 100 nmol/L increased levels of IL-6, IL-1 beta,
      MCP-1, or TNF alpha mRNA in monocytes. Differential responses of SMCs and
      monocytes to thrombin extended to early agonist-mediated increases in [Ca2+]i.
      SMCs and endothelial cells, but not monocytes, contained abundant mRNA encoding
      the thrombin receptor and displayed cell surface thrombin receptor expression
      detected with a novel monoclonal antibody. Thus, the level of thrombin receptors
      appeared to account for the differential thrombin susceptibility of SMCs and
      monocytes. These data suggest that SMCs may be more sensitive than
      monocytes/macrophages to thrombin activation in human atheroma. Cytokines
      produced by thrombin-activated SMCs may contribute to ongoing inflammation in
      atheroma complicated by thrombosis or subjected to angioplasty.

PMID- 8756007
TI  - Alterations in rat interlobar artery membrane potential and K+ channels in
      genetic and nongenetic hypertension.
AB  - The renal vasculature plays an important role in the control of blood pressure.
      K+ channels have been demonstrated to regulate smooth muscle membrane potential
      and thereby control smooth muscle tone. However, few data are available on K+
      channel function in the renal vasculature of hypertensive animals. This study
      details changes in K+ currents and membrane potential in genetic and nongenetic
      models of hypertension. The patch-clamp technique and Ca(2+)-imaging fluorescence
      were used to examine the differences in Wistar-Kyoto (WKY), Sprague-Dawley (SD),
      spontaneously hypertensive (SHR), and deoxycorticosterone acetate (DOCA)
      hypertensive single cells of rat kidney interlobar arteries. In current-clamp
      experiments, SHR and DOCA hypertensive cells were approximately 20 mV more
      depolarized than the control cells. In voltage-clamp experiments with 4-amino
      pyridine and niflumic acid present to inhibit voltage-dependent K+ (K(v)) and
      Ca(2+)-activated CI- (CI(Ca)) currents, SHR and DOCA hypertensive Ca(2+)
      activated K+ (K(Ca)) currents were significantly larger and activated at more
      negative potentials than the control. Conversely, with charybdotoxin and niflumic
      acid present to inhibit K(Ca) and CI(Ca) currents, SHR and DOCA hypertensive K(v)
      current was significantly smaller than the control. Finally, basal and
      angiotensin II-stimulated peak intracellular free [Ca2+] was greater in the SHR
      and DOCA hypertensive cells compared with control cells. These results suggest
      that membrane potential and the activity of K(Ca) and K(v) channels are altered
      in hypertensive rat renal interlobar arteries and may play a role in the
      regulation of renal blood flow under physiological and patho-physiological
      conditions.

PMID- 8756009
TI  - MAP kinase activation by flow in endothelial cells. Role of beta 1 integrins and
      tyrosine kinases.
AB  - Local alterations in the hemodynamic environment regulate endothelial cell
      function, but the signal-transduction mechanisms involved in this process remain
      unclear. We previously demonstrated that mitogen-activated protein (MAP) kinase
      is rapidly stimulated by flow in bovine aortic endothelial cells. Integrin
      receptors may act as mechanotransducers, as suggested by rapid remodeling of
      focal adhesion complexes in response to flow. To study the role of integrins in
      flow-mediated MAP kinase activation, we compared the effects of beta 1 integrin
      activation (with 8A2 antibody) and flow in cultured human umbilical vein
      endothelial cells (HUVECs). Both 8A2 (3 micrograms/mL) and flow (shear stress, 12
      dynes/cm2) stimulated MAP kinase, although the flow response was faster and
      greater. To characterize flow-activated tyrosine kinases, tyrosine-phosphorylated
      proteins were immunoprecipitated and identified by Western blot. There was a time
      dependent increase in phosphotyrosine content in 60- to 80-kD, 110-kD, 125- to
      150-kD, and 180- to 190-kD proteins. A 125-kD protein was identified as focal
      adhesion kinase (FAK), suggesting that flow activates integrins. In comparison
      with flow, 8A2 caused less tyrosine phosphorylation of fewer proteins, although
      FAK was tyrosine phosphorylated. Concurrent stimulation of HUVECs with 8A2 and
      flow caused additive increases in MAP kinase. Antibody 8A2 increased binding of
      the beta 1 affinity-sensitive antibody, 15/7, while flow failed to increase
      binding of 15/7. In summary, both a beta 1-activating antibody and flow stimulate
      tyrosine kinases, leading to activation of FAK and MAP kinase signal-transduction
      pathways. However, the cellular responses elicited by 8A2 represent only a
      portion of those stimulated by flow, suggesting that "costimulatory" events such
      as calcium mobilization, in addition to integrin activation, mediate the HUVEC
      response to fluid shear stress.

PMID- 8756008
TI  - Angiotensin II type 2 receptor-mediated regulation of rat neuronal K+ channels.
AB  - We have previously shown that angiotensin II (Ang II), via AT2 receptors,
      increases whole-cell K+ current in cultured rat hypothalamus and brain stern
      neurons. We have now investigated the AT2 receptor-mediated effects of Ang II on
      the activity of single delayed rectifier K+ channels in cell-attached membrane
      patches. In control recordings (bath, 5.4 mmol/L K+; pipette, 140 mmol/L K+), two
      voltage-dependent channels were recorded with conductances of 34 +/- 4 and 56 +/-
      6 pS, respectively (n = 6). When patches were excised, the channels reversed near
      a membrane potential expected for a K+ channel. In cell-attached patches (-40
      mV), Ang II (100 nmol/L) increased open probability of the 56-pS K+ channel from
      0.03 +/- 0.01 to 0.21 +/- 0.05 (n = 3). The selective AT2 receptor antagonist PD
      123319 (1 mumol/L) but not the AT1 receptor antagonist losartan (1 mumol/L)
      blocked the actions of Ang II (n = 3). The selective AT2 receptor agonist CGP
      42112 (100 nmol/L) produced similar effects to Ang II. Kinetic analysis of the
      Ang II effect showed that open-time histograms were best fit by two exponential
      functions. Ang II increased both open-time constants relative to control
      (control, tau 1 = 0.9 +/- 0.1 milliseconds, tau 2 = 2.3 +/- 0.3 milliseconds; Ang
      II, tau 1 = 3.1 +/- 0.4 milliseconds, tau 2 = 12.1 +/- 2.4 milliseconds), and PD
      123319 blocked this effect (n = 3). The closed-time histogram was not affected by
      Ang II PD 123319, or losartan. These results suggest that activation of AT2
      receptors modulates rat hypothalamus and brain stern neuronal whole-cell K+
      current by increasing the open probability of a 56-pS K+ channel.

PMID- 8756010
TI  - Depression of endothelial nitric oxide synthase but increased expression of
      endothelin-1 immunoreactivity in rat thoracic aortic endothelium associated with
      long-term, but not short-term, sympathectomy.
AB  - Recent pharmacological studies have shown that perivascular nerves can influence
      the development and function of vascular endothelial cells (ECs). However,
      morphological studies have not yet been carried out to investigate whether these
      functional changes are associated with changes in vasoactive substances in ECs.
      We used postembedding electron microscopy (EM) triple gold-labeling
      immunocytochemistry to study the effects of short-term sympathectomy (3 days
      after 6-hydroxydopamine [6-OHDA] treatment) and long-term sympathectomy
      (guanethidine and 8 days after 6-OHDA) on the distribution of vasoactive
      substances in ECs of the rat thoracic aorta. The post-embedding
      immunocytochemistry, which can detect levels of label in individual cells, showed
      that there was a significant decrease in endothelial NO synthase (NOS3)-labeled,
      serotonin (5-HT)-labeled, and substance P (SP)-labeled, but a significant
      increase in endothelin-1 (ET-1)-labeled, gold particles in ECs after long-term,
      but not after short-term (3-day), sympathectomy. In conclusion, our results show
      that long-term sympathectomy causes an increase in ET-1 and decrease in NOS3, 5
      HT, and SP immunoreactivity in ECs of the thoracic aorta. Our data also indicate
      that postembedding EM triple gold-labeling immunocytochemistry is a valuable
      technique for quantitative studies of the content of vasoactive substances in
      ECs.

PMID- 8756011
TI  - Rapid microvessel rarefaction with elevated salt intake and reduced renal mass
      hypertension in rats.
AB  - To identify the sequence of events associated with the development of reduced
      vessel density (rarefaction) in hypertension, microvessel density and
      ultrastructure were assessed in the cremaster muscle of rats subjected to a 75%
      surgical reduction of renal mass and normotensive sham-operated control rats.
      Rats with reduced renal mass (RRM rats) and sham-operated rats were then
      maintained on either a high salt (4.0% NaCl) or a low salt (0.4% NaCl) diet for 3
      days. Acute exposure to the high salt diet significantly increased mean arterial
      pressure in RRM rats but did not affect sham-operated control rats. Quantitative
      fluorescence microscopy of cremaster muscle whole mounts using rhodamine-labeled
      Griffonia simplicifolia I lectin revealed substantial rarefaction of microvessels
      in both RRM hypertensive rats and normotensive sham-operated rats on a high salt
      diet relative to corresponding control rats on a low salt diet. Confocal
      microscopy revealed a heterogeneous distribution of microvessels in RRM rats on a
      high salt diet, with some areas largely devoid of vessels. RRM and sham-operated
      rats on a high salt diet both exhibited changes in arteriolar ultrastructure,
      which included a loss of basement membranes and a dissociation of the endothelial
      and smooth muscle components of the vascular wall, resulting in a loss of vessel
      integrity. These observations demonstrate that a rapid loss of microvessels can
      occur not only in rats with RRM hypertension but also in normotensive rats on a
      high salt diet. This loss of microvessels results from structural alterations,
      which differ from the degenerative processes associated with microvascular
      rarefaction in rats with chronic RRM hypertension.

PMID- 8756012
TI  - Role of endothelium-derived nitric oxide in coronary vasodilatation induced by
      pacing tachycardia in humans.
AB  - Endothelium-derived NO contributes to the control of coronary perfusion. We
      investigated the roles of NO in the metabolic coronary vasodilatation induced by
      rapid pacing in humans. We evaluated the dilatation of large epicardial and
      resistance coronary arteries during rapid atrial pacing before and after
      intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO
      synthesis, in 19 patients without significant coronary artery disease. The
      diameter of the large epicardial coronary artery and coronary blood flow (CBF)
      were assessed by quantitative coronary arteriography and by a Doppler flow
      velocity measurement. An increase in the heart rate increased CBF (P < .01) and
      the coronary artery diameter (P < .05). L-NMMA at a total dose of 200 mumol
      reduced basal CBF but did not significantly affect basal coronary artery
      diameter, arterial pressure, or heart rate. L-NMMA inhibited the pacing-induced
      dilatation of the large coronary arteries (P < .05) but did not affect pacing
      induced increases in CBF. L-NMMA inhibited the acetylcholine-induced increase in
      CBF (P < .01) and acetylcholine-induced dilatation of the large epicardial
      coronary artery (P < .05). These results show that the contribution of NO to the
      metabolic vasodilatation during rapid pacing may differ between large epicardial
      and resistance coronary arteries in patients without significant coronary artery
      disease.

PMID- 8756013
TI  - Effect of tetrahydrobiopterin on endothelial function in canine middle cerebral
      arteries.
AB  - Tetrahydrobiopterin is an essential cofactor required for activation of NO
      synthase. However, in intact arteries, the exact role of tetrahydrobiopterin in
      the regulation of NO synthase activity is not fully understood. The present study
      was designed to determine the effect of increasing intracellular
      tetrahydrobiopterin levels on endothelial function in isolated canine middle
      cerebral arteries. The arterial segments were incubated in MEM for 24 hours at 37
      degrees C in the presence or absence of a tetrahydrobiopterin precursor,
      sepiapterin (10(-4) mol/L), and/or superoxide dismutase (150 U/mL). The rings
      were suspended for isometric tension recording. Tetrahydrobiopterin levels were
      assayed by high-performance liquid chromatography. Production of cGMP was
      measured by radioimmunoassay. Incubation with sepiapterin markedly increased
      intracellular tetrahydrobiopterin levels. In sepiapterin-treated arteries,
      endothelium-dependent relaxations to calcium ionophore A23187 and intracellular
      cGMP levels were significantly reduced. Superoxide dismutase alone did not affect
      either relaxation to A23187 or production of cGMP. However, when arteries were
      incubated with superoxide dismutase plus sepiapterin, endothelium-dependent
      relaxations to A23187, as well as cGMP production, were significantly augmented.
      The augmentation of cGMP was observed in rings with (but not without)
      endothelium. Incubation of arteries in calcium-free medium almost abolished the
      synergistic effect of tetrahydrobiopterin and superoxide dismutase on cGMP
      production. These results demonstrate that increased availability of
      tetrahydrobiopterin may activate endothelial NO synthase. This effect appears to
      be critically dependent on the presence of superoxide dismutase.

PMID- 8756014
TI  - Coronary and systemic hemodynamic effects of sustained inhibition of nitric oxide
      synthesis in conscious dogs. Evidence for cross talk between nitric oxide and
      cyclooxygenase in coronary vessels.
AB  - Sustained inhibition of NO synthesis (N omega-nitro-L-arginine [L-NNA], 20 mg.kg
      1.d-1, 7 days) was investigated at rest and during exercise in conscious dogs. At
      rest, L-NNA did not alter mean arterial blood pressure but markedly increased
      total peripheral resistance (+73 +/- 14%, P < .01). Exaggerated hypertension was
      observed during exercise (+132 +/- 5 mm Hg after L-NNA versus +113 +/- 5 mm Hg
      before L-NNA, P < .01). L-NNA decreased the resting coronary artery diameter by 6
      +/- 1% and suppressed its exercise-induced dilation but had no effect on coronary
      blood flow and resistance. L-NNA decreased flow repayment volumes during reactive
      hyperemia, but corresponding flow debt volumes remained unchanged. The
      cyclooxygenase inhibitor diclofenac (10 mg/kg) had no effect on reactive
      hyperemia parameters before L-NNA but reduced flow repayment volumes, durations,
      and corresponding debt-to-repayment ratios in L-NNA-treated dogs (all P < .05).
      In vitro, indomethacin blunted the residual relaxation to bradykinin of large
      coronary arteries taken from L-NNA-treated, but not from control, dogs.
      Bradykinin-induced increase in 6-ketoprostaglandin F1 alpha production was
      greater in coronary arteries taken from L-NNA-treated dogs (+ 179 +/- 41 pg/mm2)
      than from control dogs (+ 66 +/- 18 pg/mm2) (P < .05). These results indicate
      that (1) NO is of major importance in the control of systemic but not coronary
      resistance vessels at rest and during exercise, and (2) after L-NNA, the
      cyclooxygenase pathway is involved in myocardial reactive hyperemia and in the
      residual relaxation to bradykinin of isolated coronary arteries. Thus, in
      conscious dogs, the cyclooxygenase pathway might act as a protective mechanism of
      the coronary circulation when endothelial nitric oxide synthesis is altered.

PMID- 8756015
TI  - Disruption of hemoglobin oxygen transport does not impact oxygen-dependent
      physiological processes in developing embryos of zebra fish (Danio rerio).
AB  - Embryonic hemoglobin circulated by the developing heart in the early vertebrate
      embryo is widely assumed (without substantiation) to perform the same vital role
      of O2 carriage that it does in fetuses and adults. In order to challenge this
      assumption, we measured highly O2-dependent physiological variables like O2
      consumption, cardiac performance, and initial swim bladder filling in the
      presence and absence of functional hemoglobin in the embryos and early larvae of
      the zebra fish, Danio ( = Brachydanio) rerio. Functional ablation of hemoglobin
      by carbon monoxide or phenylhydrazine did not reduce whole-animal O2 consumption,
      which was approximately 85 to 90 mumol.g-1.h-1. Similarly, no differences in
      heart variables like ventricular pressure development or heart rate, which
      increased from 135 to 175 bpm between stages 36h and 96h (indicating
      developmental stages 36 and 96 hours after fertilization, respectively), were
      observed in these experiments. Initial opening of the swim bladder was not
      influenced in the presence of CO-occupied hemoglobin but was significantly
      impaired when the embryonic hemoglobin was chemically modified by incubation with
      phenylhydrazine. That aerobic processes continue without hemoglobin O2 transport
      indicates the adequacy in the embryo of simple O2 diffusion alone even in
      developmental stages with extensive convective blood circulation generated by the
      heart.

PMID- 8756016
TI  - Good laboratory practice.

PMID- 8756017
TI  - Cell death in vivo: terminal maturation, necrosis and apoptosis.

PMID- 8756018
TI  - Pathology of paediatric human immunodeficiency virus infections in Cote d'Ivoire.

PMID- 8756019
TI  - Classification and grading of squamous cell carcinoma of the cervix.
AB  - Two hundred and twenty three cases of squamous cell carcinoma of the cervix were
      classified according to their resemblance to cells in any of the layers in the
      ectocervix and a grade of low and high malignancy was also given to each case.
      Forty cases were classified as basal, 59 as prickle, 115 as intermediate and nine
      as superficial cell types. Ninety cases were high grade (seven basal, 14 prickle,
      63 intermediate and six superficial) and 133 were low grades (33 basal, 45
      prickle, 52 intermediate, three superficial). This study shows that the
      intermediate cell type is the commonest and are usually high grade tumours. The
      findings also support the idea that squamous cell carcinoma of the cervix may
      arise from any of the normal layers in ectocervix and suggests that squamous cell
      carcinoma of the cervix is not a single disease entity, but heterogenous group of
      tumours like the non-Hodgkin's B cell or T cell lymphomas. Further study is
      needed to correlate the cytokeratin subtypes and clinical features of each
      histological type.

PMID- 8756020
TI  - Effect of protein deficient cassava diet on Cercopithecus aethiops hearts and its
      possible role in the aetiology and pathogenesis of endomyocardial fibrosis in
      man.
AB  - Despite the current hypotheses for its causation, the exact cause of
      endmyocardial fibrosis is unknown. However, endomyocardial fibrosis being a
      disease of the low socio-economic groups who feed on low protein high
      carbohydrate diets consisting exclusively of cassava in Uganda and the
      demonstration by the author of a bimodal age distribution among the female
      patients and monomodal pattern in the male patients, led the author to suspect
      protein deficiency and cassava as aetiological factors thereby attributing the
      first mode to the increased but unmet protein needs for childhood growth and the
      second mode to the increased but unmet protein needs for pregnancies and
      lactation in the 20-40 year age groups. Consequently a new hypothesis that
      "prolonged ingestion of tuber (cassava/tapioca) crops associated with extreme
      deprivation of protein causes EMF" was formulated. In order to verify this
      hypothesis, three Cercopithecus aethiops were fed on uncooked banana diet while
      another three were fed on uncooked cassava and hearts harvested for histology
      whenever the animal health deteriorated. Changes in the endomyocardium included
      cell vacuolation, interstitial fibrosis and endocardial thickening by the 130th
      day in the animals on cassava but the animals on bananas were free from such
      changes. By the 160th day, the former exhibited marked thickening of the
      endocardium, interstitial fibrosis, fibrous septa formation, pappillary muscle
      fibrosis as well as apical fibrosis of the left ventricle, which findings occur
      in the human disease. Calcification and inflammatory cells were absent. A repeat
      of the experimental feeding with cassava using a batch of five animals, one of
      which survived up to seven months revealed cardiac findings similar to those seen
      at 160 days. Thus, the pathogenetic process, hitherto obscure, begins with
      cardiac cell necrosis followed by fibrosis consequent upon the failure of cardiac
      cell repair due to protein deficiency caused by the protein free cassava diets
      since the animals on bananas, which also lacked protein did not develop similar
      changes. The low plasma amino acid profiles in EMF prone subjects, the poor blood
      supply and the great apical mechanical stress are incriminated for the severe
      apical lesions. This study shows that the disease can be experimentally induced
      in the monkey thereby validating the postulated hypothesis.

PMID- 8756021
TI  - Some pitfalls in diagnosis.

PMID- 8756022
TI  - Mucin secretion by gastric carcinoma cells: PAS alcian blue stain study.
AB  - Thirty cases of gastric cancer were studied. Slides were stained with PAS Alcian
      Blue. The staining characteristics of the mucin were correlated with gross
      characteristics of the tumours and histological types. Due to the few cases
      studied, there was no observed statistical significance between the various mucin
      staining characteristics with the histological type, sex site of tumour and
      ethnicity. In 84% of cases the tumour cells secreted either neutral or mixed
      mucins. Acid mucins were demonstrated in 5 cases only. Neutral mucin is normally
      secreted by gastric epithelium and neck cells of gastric glands. The observation
      in this study suggests that those tumours which secrete neutral and mixed mucin
      probably arise from gastric epithelium, neck cells of gastric glands or colonic
      metaplasia. In those cases where the tumour produces acid mucin it is possible
      the tumour arose from areas of intestinal metaplasia.

PMID- 8756024
TI  - Effects of cassava diet on Cercopithecus aethiops livers: a case for cassava as
      the cause of both tropical splenomegaly syndrome (TSS) and endomyocardial
      fibrosis (EMF).
AB  - The aetiology of endomyocardial fibrosis (EMF) and tropical splenomegaly syndrome
      (TSS) though speculative, was considered by the author to be the same or related
      since the two diseases may occur in the same individual and locality.
      Accordingly, when attempting to prove a hypothesis for the causation of EMF that
      prolonged ingestion of tuber (cassava/tapioca) associated with extreme
      deprivation of protein causes EMF; one group of three Cercopithecus aethiops was
      fed on uncooked cassava while a second group was fed with uncooked bananas and in
      addition to harvesting the hearts whenever the animal health deteriorated, livers
      were also harvested for histological changes. While hearts from the animals on
      cassava revealed changes seen in human EMF the livers from the same animals
      exhibited Kupffer cell hyperplasia and hypertrophy as well as sinusoidal
      lymphocytosis, features seen in human TSS thereby confirming that the aetiology
      of these two diseases is the same. However, the banana diet did not produce such
      changes.

PMID- 8756023
TI  - Serum iron, zinc, copper and bromine in malnourished children in Dar es Salaam,
      Tanzania.
AB  - We measured the serum concentration of iron, zinc, copper and bromine in fifty
      malnourished children and twenty one healthy controls using energy dispersive X
      ray fluorescence spectrometry. The mean ages for the study group and controls
      were 27.06 and 29 months respectively. The mean weights of the study and control
      groups were 7.32 and 12.05 +/- 3.07 kilogrammes respectively. The serum iron,
      zinc, copper and bromine mean levels in the study and control groups were Fe 14.6
      (9.9) Zn 12.5 (11.9) Cu 16.5 (21.2) and Br 59.1 (63.0) micromoles per litre.
      Analysis of variance between the study group and controls showed a significant
      fall in copper levels even when adjusted for age sex and weight differences (F =
      4.6586 p < 0.05). The wide distribution of concentrations of Iron noted in the
      malnourished children is probably due to haemolysis and rapid catabolism. The
      role of bromine in nutrition is yet to be established.

PMID- 8756025
TI  - Effect of HIV infection on the incidence of lymphoma in Africa.

PMID- 8756026
TI  - Control of diarrhoeal diseases programme: the Kenyan situation.

PMID- 8756027
TI  - Infant feeding practices, socio-economic conditions and diarrhoeal disease in a
      traditional area of urban Ilorin, Nigeria.
AB  - A cross-sectional study involving 771 children under the age of one year, was
      carried out in a traditional area of urban Ilorin, Nigeria, to determine how
      socio-economic conditions and feeding practices relate to diarrhoeal disease
      among infants. After adjustment has been made (through logistic regression) for
      covariates, five factors had significant association with diarrhoeal disease.
      These are the age of the child, parity, mother's education, availability of
      household kitchen and the feeding of semi-solid food to the infants. The lowest
      diarrhoeal rate occurred in infants aged 0-3 months while the highest rate
      occurred among infants seven to nine months old (Odds Ratio = 4.2). Children who
      were of the fifth or higher birth order had significantly higher risk of
      diarrhoea when compared with those who were of the first or second birth order
      (OR = 1.62; P < 0.05). Children of mothers with secondary education had
      significantly higher risk of diarrhoea compared with children of illiterates (OR
      = 1.9; P < 0.05). Households that had no kitchen had significantly higher risk of
      infantile diarrhoea than households with kitchen facilities (P < 0.01). Finally,
      infants receiving semi-solid food had higher risk of diarrhoea compared to those
      children not receiving semi-solid food (P < 0.05). Diarrhoeal disease awareness
      campaign to educate mothers on the dangers of childhood diarrhoea and how to
      prevent it, through proper hygiene, especially, food hygiene, is advocated.

PMID- 8756028
TI  - Fluid intake and feeding practices during diarrhoea in Odukpani, Nigeria.
AB  - This study was designed to determine the fluid intake and feeding practices among
      under five year old children during episodes of diarrhoea. Fluid intake was low.
      The average amount of salt-sugar solution (SSS) and WHO/UNICEF recommended oral
      rehydration solution (ORS) formula drank within the preceding 24 hours of
      diarhoea was 368 mls and 274 mls respectively. Only 54.0% and 43.3% of children
      received same or more food and fluid respectively as compared with before the
      diarrhoea. Less than half of the children continued breastfeeding. Targeted
      health education, with emphasis on these findings, are recommended for improving
      fluid and food intake in the home management of diarrhoea.

PMID- 8756029
TI  - Detection of anti-HIV-1 IgG antibodies in whole saliva by GACELISA and Western
      blot assays.
AB  - The present study, based on 158 HIV seropositives and 167 HIV seronegatives,
      demonstrates that saliva collected with the Omni-SAL device and tested with
      GACELISA (an IgG antibody capture ELISA) is an effective non-invasive alternative
      to serum for anti-HIV IgG antibody screening. The study also shows that a
      conventional serum Western blot kit can be used, with slight modifications, for
      confirmatory testing of saliva specimens. Collecting saliva with the Omni-SAL
      device had a very good acceptance rate among Tanzanian subjects, and although
      this diagnostic method is not yet known by the general public, 65% of the study
      participants preferred to give saliva instead of blood for HIV testing.

PMID- 8756030
TI  - AIDS-related knowledge and misconceptions among high secondary school teachers
      and students in Kassala, Sudan.
AB  - An AIDS-related knowledge study was carried out on a sample of 462 high secondary
      school teachers and students, in Kassala, eastern Sudan. The results showed high
      scores of knowledge about AIDS-transmission and general knowledge about the
      disease. However, there was a high frequency of AIDS-related misconceptions,
      especially among females and among teachers and students in the science education
      track. The study calls for more focus on these misconceptions in health education
      campaigns regarding AIDS.

PMID- 8756031
TI  - Sentinel surveillance and cross sectional survey on HIV infection prevalence: a
      comparative study.
AB  - Despite widespread use of sentinel surveillance systems in monitoring the
      magnitude of HIV-1 infection in populations, little is known of how the trends
      they produce compare with those of the larger populations which they support to
      represent. The objective of this study, therefore, was to assess how useful
      sentinel surveillance data on HIV-1 infection might be in estimating the
      magnitude of HIV-1 infection in the general population. To achieve this, results
      from a population based study on HIV-1 infection in Bukoba town were compared
      with those from antenatal mothers and blood donors, all from the same town. The
      studies were done during the period of 1987-90. The overall HIV-1 prevalence was
      highest in the general population sample at 24.2% (95% CI 20.6-27.8) followed by
      that in antenatal mothers at 22.4% (95% CI 20.6-25.2) and lowest in blood donors
      at 11.9% (95% CI 9.1-15.3). Seroprevalence among antenatal clinic attenders was
      significantly lower than that of females from the general population sample (p =
      0.016). Prevalence among female blood donors did not differ significantly from
      that of females from the general population sample (p = 0.06). Blood donor males
      had a lower HIV-1 seroprevalence when compared to that from the general
      population males (p = 0.038). The age group 25-34 years had the highest
      prevalence of HIV-1 infection in all the three populations indicating that this
      group is at the highest risk of HIV infection and that the three populations show
      a similar trend of age specific prevalence. From these findings, it is noted that
      female blood donors as a sentinel population represents more closely estimates of
      HIV-1 seroprevalence of females in the general population than antenatal clinic
      attenders or male blood donors. Further studies are proposed in different
      settings in order to come up with guidelines on the methodology of using sentinel
      surveillance populations in monitoring HIV-1 infection.

PMID- 8756032
TI  - Vitamin A deficiency: a serious threat in Dodota district in central Ethiopia.
AB  - A total of 147 children, aged from six months to six years were examined for
      signs of xerophthalmia in a village in Arsi zone of Ethiopia. Night blindness,
      Bitot's spots, corneal ulceration and corneal scars were observed in 17.0%,
      26.5%, 2.7% and 0.7% of the children respectively. The concentration of serum
      retinol was measured in all children with xerophthalmia and every twentieth of
      the remaining children. Serum retinol levels were in the deficient range (< 0.35
      mumol/I) in 31.9% and low (0.35-0.69 mumol/I) in 48.9% of the children. There was
      a higher prevalence of stunting (24.5%) than wasting (18.4%) with an additional
      10.2% of children being both stunted and wasted. The prevalence of diarrhoea was
      twice as high in children with xerophthalmia than children without (p < 0.01).

PMID- 8756033
TI  - Viral hepatitis.
AB  - The list of hepatitis viruses is increasing over the years. Now the viruses range
      from A to G. Hepatitis A virus is a short incubation RNA virus which is
      transmitted oro-faecally. It does not cause chronic illness but may be fatal in a
      few cases especially in pregnancy. It can now be prevented by vaccination.
      Hepatitis B virus is a long incubation DNA virus which is transmitted mainly
      through blood and blood products. It causes chronic illness and can lead to liver
      cancer in some cases. It can be prevented by vaccination and WHO is now
      recommending global vaccination of all infants irrespective of endemicity of
      hepatitis B virus. Hepatitis C virus is an RNA virus which used to be known as
      parenterally transmitted non A non-B virus. It leads to chronic illness and can
      lead to liver cancer. It is now responsible for most cases of post transfusion
      hepatitis in Europe, North America and Asia. Hepatitis Delta virus is a defective
      virus which requires hepatitis B virus for its existence. Thus it affects only
      those who have hepatitis B virus. Hepatitis E virus used to be known as the
      enterically transmitted non-A non-B virus. It is transmitted oro-faecally and
      seems not to lead to chronic illness. It is endemic in some areas like Middle
      East and parts of Africa. Hepatitis G virus is just being described. More
      information about it will soon be available.

PMID- 8756034
TI  - Adverse cutaneous reactions to systemic drugs in adults seen in two referral
      centres in northern Saudi Arabia.
AB  - One hundred and thirty seven adults with adverse cutaneous reactions to systemic
      drugs seen in two referral centres in northern Saudi Arabia, over a period of
      three years were reviewed. Urticaria, sometimes occurring with angioedema was the
      most common pattern observed. It was seen in 35% of cases and the culprit drugs
      in most instances were the salicylates and the penicillins. The combination of
      trimethoprim and sulfamethoxazole was the culprit drug in 70% of cases of fixed
      drug eruptions and 75% of cases of erythema multiforme. Although there were no
      recorded fatalities, there was prolonged morbidity in patients with the Stevens
      Johnson's syndrome, and unsightly residual hyperpigmentations in those with fixed
      drug eruptions. The occurrence of these adverse reactions were frequently
      associated with inappropriate polypharmacy and this practice should be
      discouraged.

PMID- 8756035
TI  - Intestinal obstruction in Khartoum.
AB  - The pattern of intestinal obstruction at Khartoum Teaching Hospital was reviewed
      in this study which included 239 patients. 170 of them were males and 68 were
      females. Their ages ranged from two days to 95 years (mean 31.4 +/- 5.3 years).
      The commonest causes of intestinal obstruction were strangulated external hernias
      (27.7%), intestinal adhesions (21%), intussusception (12%) and sigmoid volvulus
      (11%). Less frequent causes were paralytic ileus, large bowel tumours, peritoneal
      bands and Hirschsprung's disease. Of the strangulated hernias, inguinal hernia
      (70%) was the most frequent type of hernia seen, followed by paraumbilical hernia
      (20%). Previous appendicectomy (40%) and laparotomy for abdominal trauma (20%)
      were the commonest causes of adhesive intestinal obstruction. The mortality rate
      of intestinal obstruction was 19.7%. This high mortality is attributed to delayed
      presentation, fluid and electrolyte imbalance, intestinal ischaemia and gangrene.
      This could be minimised by health education, adequate preoperative preparation,
      meticulous surgical technique and good postoperative care.

PMID- 8756036
TI  - Reasons underlying failure to seek dental treatment among Nairobi University
      students.
AB  - A survey of 272 University of Nairobi undergraduate students was undertaken to
      assess their dental chairside experience and what reasons they gave for failing
      to seek dental treatment. Most respondents considered dental treatment
      uncomfortable and painful. The cost of treatment and fear arising from
      information given by other dental patients were important reasons that kept the
      respondents from visiting a dental clinic. This paper reveals the need for the
      dental profession to play a greater role in reducing costs of treatment and
      odontophobia.

PMID- 8756037
TI  - A comparative bioavailability of four Carbamazepine tablet formulations available
      in the Kenyan market.
AB  - The relative bioavailabilities of three carbamazepine tablet formulations
      available in the Kenyan market (Temporal(R), Taver(R) and Carbamazepine Lincoln)
      compared with the innovator formulation (Tegretol(R)) were evaluated in seven
      healthy African volunteers (5 males, two females; aged 22-36 years), according to
      a randomised fourway crossover study design, following oral administration of
      single 200 mg doses with a three week washout period. In vitro dissolution
      profiles of the tablets were also evaluated. Relative bioavailabilities ((F)rel)
      of Temporal(R), Taver(R) and Carbamazepine Linocoln were 101.2%, 82.2% and 71.6%
      respectively, compared with Tegretol(R). Percent drug content dissolved in vitro
      after I hour were 91.3%, 75.9% and 39.3% for Temporal(R), Taver(R) and
      Carbamazepine Lincoln, respectively. It was concluded that Temporal(R) was
      bioequivalent to Tegretol(R) while Taver(R) and Carbamazepin Lincoln were
      bioinequivalent to Tegretol(R). Administration of Taver(R) or Carbamazepine
      Lincoln might lead to poor control of epileptic seizures.

PMID- 8756039
TI  - Community health assessment index content and face validation studies.
AB  - The objective of the study was to evaluate content and face validity of Community
      Health Assessment Index (CHAI). Two independent groups of experts convened in Dar
      es-salaam and Eldoret after having had a chance to study CHAI for two or more
      weeks in order for them to make written evaluations on the index. Twelve and 11
      experts representing a broad range of interest in community health in the African
      context convened in Dar-es-salaam and Eldoret respectively. Most of these were
      nominated by their respective institutions, namely, ministries of health,
      academic and research institutions and non-governmental and multilateral
      organisations. The findings of the two groups of experts were very similar. The
      consensus was that CHAI has face and content validity. However, both groups
      suggested that (i) total adult mortality instead of male adult mortality be used;
      and (ii) that a 5 km rather than 10 km radius be used to define accessibility to
      health care. Regarding to questionnaire the consensus was that (a) the questions
      were both clear and culturally appropriate; (b) apart from the part which
      concerns a description of health services policy and community participation, the
      questionnaire could be administered by literate primary health care workers after
      appropriate training and translation; and (c) in addition to generating CHAI
      scores, the data gathered with this instrument could be used for planning and
      evaluation at the local community level. Overall the questionnaire was judged as
      "good" by 19 while the remaining 4 judged it as being "very good". Several
      suggestions in wording were made. Also a few additional questions were suggested.
      This evaluation provides justifications for further studies to assess the
      remaining measurement properties of this index.

PMID- 8756038
TI  - Patient attitudes to prenatal screening and termination of pregnancy at Groote
      Schuur Hospital: a two year prospective study.
AB  - A prospective 2-year study involving a questionnaire administered by a Genetic
      Counsellor was carried out to ascertain patient attitudes to prenatal screening
      and termination of pregnancy (TOP) at Groote Schuur Hospital. Women were
      questioned regarding their religious affiliation, education, ethnic group, reason
      for referral and age. Following ultrasonography, non-directive counselling was
      given regarding amniocentesis and TOP. Four hundred and sixty six women were
      investigated of whom 74% were of mixed ancestry, 14% Black and 12% White. Three
      hundred and sixteen persons were offered amniocentesis (67.8%). Muslim women
      accepted less frequently (66%) than other religious affiliations (79.7%) (p =
      0.025). Overall amniocentesis acceptance was 75.9%. TOP was performed in 45
      pregnancies (9.7%). Muslim women accepted TOP 1.33 times (C.I. 0.32-5.6) more
      frequently than those of other religious persuasions. Overall TOP acceptance rate
      was 76.3%. The mixed ethnic population of pregnant women seen at Groote Schuur
      Hospital readily accept prenatal screening and TOP following non-directive
      genetic counselling. The introduction of prenatal screening programmes for the
      prevention of severe congenital defects in this population would be successful
      and cost-effective.

PMID- 8756040
TI  - Periampullary tumours: report of two cases.
AB  - Periampullary tumour in two Ethiopian patients are described. The first patient,
      a 60 year old non-insulin dependent diabetic woman with ampullary adenocarcinoma,
      presented with symptoms, signs and laboratory results suggestive of obstructive
      jaundice and iron deficiency anaemia. The second patient, a 40 year old lady with
      duodenal adenocarcinoma, presented with dyspepsia and weight loss of 15
      kilogramme. The clinical presentation, diagnosis, and management of periampullary
      tumours are discussed with review of the literature.

PMID- 8756041
TI  - Stomal malignant transformation of respiratory papilloma, with neck metastasis:
      case report.
AB  - A case of spontaneous malignant transformation at the mucocutaneous junction of
      the tracheostomy site in a child with recurrent respiratory papilloma is
      presented. A paratracheal neck metastasis also developed in the same patient in
      early adulthood. The respiratory papillomata were first noted at the age of 1.5
      years, stomal malignancy at age of seven while the neck mass at age 14 years.
      During the prolong course of 13.5 years, the papillomas were growing
      aggressively, mainly in the trachea and main bronchi. Repeated excisions,
      radiotherapy and a variety of drugs were tried and discussed. The importance of
      close observation and follow-up is stressed. Currently at the age of 16 years,
      the patient is alive and well and leading normal activities.

PMID- 8756042
TI  - Drug abuse among urban as compared to rural secondary schools students in Kenya:
      a short communication.
AB  - In a comparative study of drug abuse in Urban versus Rural secondary schools, 952
      students (547 Urban and 405 rural) were subjected to the WHO youth survey
      questionnaire. It was found that male students abused drugs more often than
      female students. Alcohol emerged as the most commonly abused drug (15% and 14% in
      urban and rural schools respectively). Tobacco, cannabis and inhalants followed
      in that order. The "hard' drugs were more commonly used in the rural schools.

PMID- 8756043
TI  - Current management of breast cancer.

PMID- 8756044
TI  - Breast cancer and conservative surgery in sub Saharan Africa.
AB  - This study investigated the profile of breast cancer patients in Tanzania during
      1974-87 period. The results were compared with those of African patients in
      countries south of the Sahara. The maximum number of patients with breast cancer
      were seen in the sexually active age groups. In Sudan breast cancer was in
      leading position amongst all female cancers but with a lower proportion of women
      below 30 years, 6.4% (95% CI 5.3-7.6); x2 = 7.3 (p = 0.006). While in other sub
      Saharan countries the disease ranked second to cervical cancer in frequency, but
      with a high proportion of patients below 30 years of age. This proportion was
      highest in Nigeria when compared with other African countries studied 14.7% (95%
      CI 8.9-22.3); x2 = 3.9 (p = 0.04). Mastectomy continues to be the treatment of
      choice for breast cancer in the sub Saharan countries despite the fact that this
      procedure is resented. Also that the Halstedian principle which governed the
      treatment of the disease for a century now has been disputed regarding its
      usefulness. The biological basis for adopting conservative surgery for breast
      cancer, the need for early detection and the oncogenesis of the disease are
      discussed.

PMID- 8756045
TI  - Serological investigation of HIV-1 variant subtype strains in transmission in
      Nairobi.
AB  - In a bid to determine the HIV-1 subtype variants in transmission in Nairobi and
      its possible association with clinical status, we screened 207 confirmed HIV-1
      positive patients visiting HIV/AIDS laboratory at the Virus Research Centre in
      Nairobi between January and March 1994. We used a selfmade ELISA obtained from an
      established panel of HIV-1 V3 loop peptides (ANRS, France) and derived from seven
      isolates: MN, HXB2, SC, Z6, Z2, ELI and CDC4. Test samples were obtained from 95
      blood donors and medical examination attendees, 57 patients with chronic
      diarrhoea, 31 confirmed pulmonary tuberculosis, 16 with pneumonia and 12 herpes
      zoster. Out of the total, 21.5% had antibodies against the MN strain, 19.1% had
      against the Z2 strain while reaction against the HXB2 strain was observed in
      17.2%. SC, CDC4, Z6 and ELI had prevalences of 11.5%, 6.2%, 5.3% and 3.8%
      respectively. Fifteen per cent of the tested sera showed no reaction to any of
      the used peptides. Strong and significant associations were observed between the
      total number of strains a sample react to and the clinical state. We infer that
      both the North American consensus strains (MN and HXB2) and the African isolates
      (Z2 and Z6) are predominant in Nairobi. The correlation between antibody
      reactivity and clinical state is an interesting observation that necessitates an
      expanded study and, the use of strain specific peptides maybe a sensitive and
      easier method for use for molecular epidemiological purposes.

PMID- 8756047
TI  - Adolescent sexual behaviour, knowledge and attitudes to sexuality among school
      girls in Transkei, South Africa.
AB  - Teenagers make up a quarter of all mothers in Transkei, South Africa, and well
      over 75% of them are unmarried. Such a high rate of teenage pregnancy is
      indicative of a high level of unprotected adolescent sexual activity. We examined
      sexual behaviour, knowledge and attitudes to sexuality among adolescent school
      girls in Transkei, using a self-administered questionnaire, in order to establish
      the incidence of sexual activity, and associated risk factors. Of the 1072
      respondents, 74.6% were already sexually experienced, and 21.0% were not. The
      majority of sexually experienced girls (SEGs) and sexually inexperienced girls
      (SIGs) were living with both their parents. There were no religious differences
      between the two groups of girls. The age of SEGs at first coitus correlated
      positively with the age of menarche, and the age at the first date, suggesting
      that sexual maturation and onset of dating were possible risk factors for
      initiation of sexual activity. Contraceptive use was low, and a third of SEGs had
      been pregnant at least once. The knowledge of reproductive biology among both
      groups of girls was generally poor, although SEGs were significantly more
      knowledgeable than SIGs. The majority of girls in both groups did not approve of
      premarital sex, and adolescent pregnancy. They also did not approve of the idea
      of introducing sex education in schools, or the provision of contraceptives by
      schools. Nearly a third of the respondents in both groups did not wish to get
      married in future. In conclusion, there is a high level of unprotected sexual
      activity among school girls in Transkei. The risk factors for this include early
      sexual maturation, early onset of dating, and poor knowledge of reproductive
      biology and contraceptives.

PMID- 8756046
TI  - Obstetrics service utilisation by the community in Lebowa, northern Transvaal.
AB  - A cross sectional cluster survey was done in all health wards of Lebowa in May
      1992. The study was based on a recall of antenatal, intrapartum and postnatal
      experience during the last pregnancy of 2940 mothers. Only mothers who delivered
      within 12 months before the date of interview were included. Antenatal coverage
      was high at 93.5%, the proportion of health facility deliveries was 74.6% while
      26.3% of all births occurred at home. Inaccessibility of maternity services, lack
      of money, negative staff attitudes and lack of privacy were the common reasons
      given for preference of home delivery. Mothers who delivered at home were more
      likely to be of higher parity and unbooked than their counterparts who delivered
      in a health facility. Postnatal coverage was 50.7% with a 25.4% rate of
      utilisation of a method of childspacing. The proportion of births attended to by
      trained personnel needs to be increased.

PMID- 8756049
TI  - Hospital acquired pre-prostatectomy bacteriuria: risk factors and implications.
AB  - One hundred and one consecutive prostatic patients with sterile urines were
      prospectively studied for the risk factors involved in the hospital acquired pre
      prostatectomy bacteriuric and its implications. Eleven out of 101 patients (11%)
      became bacteriuric at operation whereas ninety of 101 patients (89%) remained
      abacteriuric. Nine of the eleven bacteriuric patients (82%) had pre-operative
      indwelling urethral catheters compared to 37/90 (41%) abacteriurics (P < 0.05).
      Mean catheter duration was 22.22 and 9.92 days respectively (P < 0.05). Three out
      of eleven (27%) bacteriuric patients had chronic retention of urine compared to
      one of ninety (1%) abacteriuric patients. Past history of acute retention,
      vesical stones, vesical diverticulae, diabetes mellitus and azotaemia were not
      significant risk factors. Post-operative fever did not correlate with positive
      blood cultures. However, eight of the eleven (73%) bacteriurics developed
      bacteraemia compared to only one out of ninety (1%) abacteriuric patients. It is
      concluded that the significant risk factors which would be strong indications for
      antimicrobial prophylaxis in prostatectomy are chronic retention of urine and
      prolonged pre-operative indwelling urethral catheterization for more than ten
      days. Azotaemia, diabetes mellitus and associated bladder pathologies were not
      significant and therefore do not warrant antimicrobial prophylaxis.

PMID- 8756048
TI  - Preliminary comparison of the polyurethane female condom with the latex male
      condom in Kenya.
AB  - This paper summarizes acceptability data published to date on the innovative
      female condom, and presents an additional study comparing the acceptability of
      the female condom and the latex male condom in a sample of low risk women
      attending private obstetrician/ gynaecologists' clinics in Nairobi, Kenya. Eighty
      four percent of all subjects who completed interviewer-assisted questionnaires
      reported that they liked using the female condom, and more than two-thirds of all
      the women liked the female condom as much or better than the male condom. Fifty
      five percent of the women would use the device in future if it were available.
      The least liked features were that the device was too large for easy insertion,
      messy to handle, and reduced sensation. Use became easier and more comfortable
      with experience. The most liked features were that the device made sex more
      enjoyable, protected against sexually transmitted diseases and pregnancy, and was
      under the woman's control. Male partner response was slightly less favourable,
      and sometimes resulted in women's noncompliance or discontinuation of use,
      despite the fact that such a device is supposed to empower women. This study
      provides preliminary data indicating that the female condom is a fairly
      acceptable method for some Kenyan couples, but recommends further research into
      safety, cost-effectiveness and hindrances to acceptability.

PMID- 8756050
TI  - Disposition of quinine in plasma after a single oral and intramuscular dose in
      healthy adult Africans.
AB  - The pharmacokinetics of quinine were assessed in healthy adult Africans after a
      single oral dose of 500 mg quinine base (n = 11) and after a single intramuscular
      injection of 500 mg quinine base (n = 7). Quinine was assayed in plasma by high
      performance liquid chromatographic method (HPLC). Quinine was rapidly absorbed
      reaching a mean peak concentrations of 2.9 (sd 0.5) and 4.5 (1.3) mg L-1
      respectively in a median time of 3.0 (range 2.0-4.0) and 1.5 (range 0.5 4.0) h
      respectively after oral and intramuscular administration. The peak concentration
      (Cmax) was significantly higher after intramuscular than after oral
      administration [Cmax = 4.5 (1.3) versus 2.9 (0.5) mg L-1, p < 0.01]. The mean
      half-life [t1/2z = 11.7 (2.9) versus 10.7 (3.5) h, P > 0.2] respectively, volume
      of distribution (Vz = 2.5 (0.7) versus 2.2 (0.99) L Kg-1, P > 0.2) respectively
      and estimated plasma clearance [CLp = 0.15 (0.04) versus 0.15 (0.09) L h-1 Kg-1,
      P > 0.2] respectively were not significantly different after oral and
      intramuscular administration. The mean AUCo-oo was higher after intramuscular
      than after oral administration [71.8 (29.4) versus 54.9 (19.2) mg.h.L, P > 0.1]
      respectively but this was not significant. The pharmacokinetic parameters after
      intramuscular dose were similar to those obtained in seven healthy subjects given
      quinine by slow intravenous infections over four hours. The dose was well
      tolerated.

PMID- 8756051
TI  - Prescription writing in Gondar outpatient teaching hospital, Ethiopia.
AB  - A total of 19,119 prescriptions consecutively written between January-July 1992
      were collected from Gondar outpatient hospital selling pharmacy and reviewed to
      determine physician's adherence to the basic principles of prescription order
      writing. In 36.6%, 16.8% and 12.4% of the prescriptions, respectively, age, sex
      and chart numbers of patients were not recorded. Twelve percent, 7%, 6.4%, 5.8%
      and 1.6% of the prescriptions did not indicate routes of drug administration,
      directions for drug use, frequency of drug administration, drug dose and duration
      of treatment, respectively. No prescription order had special advice or warnings
      to the patient and in 10.8% of the cases date was omitted. Out of the dispensed
      drugs, 82.9% were written in generic names and over 70% were included in the
      Essential Drug List of Ethiopia. The five most commonly dispensed individual
      drugs were ampicillin (10.4%), paracetamol (9.5%), TB 450 + isoniazid (7.4%),
      penicillin G (6.8%) and aspirin (5.8%). As therapeutic classes, antiinfectives
      were most common (47.8%) of which antibacterials constituted 38.1%, followed by
      analgesic-antipyretics (17.5%). Most drugs were prescribed by young medical
      interns and dispensed by less qualified personnel. Our preliminary survey
      indicates that essential components of a prescription order were omitted to a
      great extent and suggested to modify the existing undergraduate
      pharmacotherapeutic teaching in order to promote rational use and prescribing
      before bad habits get a chance to develop. The type of drugs dispensed at the
      selling pharmacy could not be beneficial to the patient without competent
      professional patient counselling, delivery of correct information as well as
      appropriate prescription monitoring.

PMID- 8756052
TI  - Essential drugs supply and usage as a reflection of outpatient morbidity in
      Kirinyaga District, Kenya.
AB  - This study was carried out in all the twenty eight Government rural health
      facilities (RHF's) in Kirinyaga District of Kenya. It aimed at determining
      whether the quantities and types of drugs supplied to the RHF's matched the
      morbidity patterns, and also whether the disease patterns continued to be used as
      a basis for requesting stocks of essential drugs. It also investigated the
      constraints associated with the programme with an ultimate aim of improving
      service delivery. The information was obtained through records review of the Bin
      card books, Out-patients Department (OPD) register, morbidity monthly returns,
      staff and patient interviews. A highly significant (p < 0.01) variation in
      morbidity (workload) by season of the year and between the ecological divisions
      of the district was observed. Significant differences were also observed between
      the quantities of drugs supplied and the actual monthly requirements in all the
      RHF's, implying that the disease patterns were not necessarily being used for
      requesting stocks of essential drugs. A distribution of essential drugs based on
      two broad ecological divisions of the district was recommended. One of the major
      constraints found to be associated with the Essential Drugs Programme was the
      delay in procurement/distribution of essential drugs to the RHF's. This was
      mainly due to the tendering procedures of Kit 2 by the Ministry of Health (MOH)
      and also occasional lack of transport at the district level.

PMID- 8756053
TI  - Bone involvement in childhood acute lymphoblastic leukaemia.
AB  - This retrospective study evaluated the prognostic significance of the
      radiological signs of bony involvement in children with acute lymphoblastic
      leukaemia (ALL). The skeletal surveys of 52 children with ALL were reviewed for
      evidence of leukaemic involvement. Radiolucent metaphyseal bands, osteolytic
      lesions and periosteal reaction were considered signs of leukaemic changes.
      Twenty eight children had evidence of skeletal involvement of whom 14 had changes
      at three or more areas. Known risk factors such as age < 2 years and > 10 years,
      mediastinal lymphadenopathy, splenomegaly > or = 5 cm below the costal margin, a
      white cell count of > or = 20 x 10(9)/l and leukaemic blast cells in the
      cerebrospinal fluid at diagnosis occurred with equal frequency in children with
      and without skeletal changes as well as those children with signs of involvement
      at > or = 3 sites. Event free survival (Kaplan Meier analysis) also did not
      differ in these three categories of children. We concluded that bone involvement
      in childhood ALL is not associated with other risk factors and does not predict
      outcome per se.

PMID- 8756054
TI  - Seminoma arising in cryptorchid testes in Nigerian males.
AB  - Histological slides of seventy four patients with testicular malignancy found in
      the records of the cancer registry, University College Hospital, Ibadan over a
      thirty-five year period (1960-1994) were reviewed. Three (4%) cases occurred in
      undescended testes. Overall, eighteen (24.3%) patients were found to have
      seminomas. All the tumours seen in undescended testes (100%) were seminomas while
      about seventeen percent of seminomas were seen in undescended testes. There was a
      statistically significant difference between the mean ages of those with
      seminomas (37.6 years) and those with non-seminomatous testicular cancers (30.3
      years); t = 1.69; p < 0.05. The numbers seen corroborate the fact that testicular
      cancers are not very common in this environment. The incidence of undescended
      testes is not established in this environment either. However, it seems that 100%
      of tumours arising in undescended testes are seminomas. It is recommended that
      abdominal testes seen after puberty should be removed and older patients
      presenting with abdominal masses should have a differential diagnosis of
      testicular cancer entertained.

PMID- 8756055
TI  - Consultation-liaison psychiatry in a general hospital setting in west Africa.
AB  - This study examined the pattern of psychiatric consultation-liaison service in a
      West African general hospital setting over a period of five years. Cases seen
      were recorded in a register and later analysed. The rate of referral was found to
      be lower than those of Britain and USA. Most of the patients seen were young
      persons between the ages of 16 and 45 years. The predominant physical disorders
      complicated by psychopathology were infective disorders, neurological disorders,
      cardiovascular, and obstetric conditions. The commonest psychiatric syndromes
      encountered were acute brain syndrome, brief reactive psychosis, depressive
      disorder and dementia. A negative attitude towards patients with psychiatric co
      morbidity was identified. Areas of improving consultation-liaison psychiatric
      services in West Africa are suggested.

PMID- 8756056
TI  - A clinical sign for persistent harmful cannabis abuse?: a pilot study.
AB  - Eight patients made up of four psychotics with known history of harmful cannabis
      use and four psychotics with no history of cannabis use together with four
      subjects, who were non-psychotic, non-smokers were studied. The aim of the study
      was to ascertain the reliability of a clinical sign of ulceration of the pulps of
      the first and second fingers. Photographs of the fingers were taken and were
      examined by a dermatologist. The finding clearly demonstrated that those patients
      with a history of harmful cannabis use showed the ulceration whilst the other
      psychotics with no known history of cannabis use as well as the control subjects
      showed no such features. It is suggested that a larger sample should be studied
      and if the findings prove consistent then it could be readily used to
      differentiate between harmful cannabis use and functional psychosis.

PMID- 8756057
TI  - Ascaris suum: ultrastructural effect of in vitro albendazole therapy.
AB  - The effect of albendazole therapy on adult Ascaris suum was examined using
      transmission electron microscopy. The drug induced prominent ultrastructural
      changes which included the presence of necrotic dense bodies, myelin whorls which
      appeared to represent various stages of lysosomal formation and autolysis,
      disruption and erosion of the microvilli. The effects were mainly confined to the
      central region of the intestinal epithelial cells.

PMID- 8756058
TI  - Hydrogen peroxide in the regulation of erythropoietin (Epo) gene expression in
      hepatocellular carcinoma cells.
AB  - The present studies were designed and carried out to determine if hydrogen
      peroxide (H2O2) is involved in the regulation of erythropoietin (Epo) gene
      expression and stimulation of Epo production in the hepatocellular (Hep 3B)
      cells. Hep 3B cells were incubated with varying concentrations of H2O2 for
      periods of 6 hours or 24 hours. In other experiments Hep 3B cells were incubated
      for 24 hours with or without increasing concentrations of catalase and in the
      presence of H2O2. Culture medium levels of Epo were determined and quantitation
      of Epo mRNA was also made. The results indicate that H2O2 increases the levels of
      Epo mRNA and Epo hormone production in Hep 3B cells, and that catalase, the
      specific scavenger of hydrogen peroxide, inhibits Epo production in these cells.
      Based on these findings, it is concluded that H2O2 takes part in the signal
      transduction mechanisms in Epo production. It is recommended that further studies
      be undertaken to find out the source of the hydrogen peroxide in the
      hepatocellular carcinoma cells.

PMID- 8756060
TI  - Extramedullary plasmacytoma of anorectum: case report.
AB  - A young anxious looking male presented with a referral diagnosis of recurred
      bilateral ischiorectal abscesses. Clinical examination and investigations showed
      an advanced lesion of the anorectum. Histology revealed an extramedullary
      plasmacytoma of the anorectum to which the patient succumbed and died within two
      weeks of presentation.

PMID- 8756059
TI  - Extraperitoneal hypogastric artery ligation in control of intractable haemorrhage
      from advanced carcinoma of cervix and choriocarcinoma.
AB  - Seven cases of extraperitoneal ligation of the hypogastric arteries to control
      bleeding from advanced cervical cancer and choriocarcinoma is presented. This
      method was able to arrest haemorrhage and there was no further transfusion. The
      surgical technique and advantages are described.

PMID- 8756061
TI  - Bilateral primary malignant lymphoma of the testis: case report.
AB  - A nineteen year old Kenyan male presented with a twelve month history of rapidly
      progressing painless swelling of both testicles. Pre-operative clinical and
      laboratory evaluation resulted in clinical suspicion of bilateral testicular
      tumour confirmed by ultrasonography. Bilateral inguinal orchidectomy was effected
      and histology confirmed bilateral primary malignant lymphoma of the testis in a
      nineteen year old regarded as a rare and unusual presentation.

PMID- 8756062
TI  - Adoption: an overview.

PMID- 8756063
TI  - The role of the perinatal nurse in open adoption.

PMID- 8756064
TI  - Expanding on HIV infection in women and children.

PMID- 8756066
TI  - Systematic neonatal assessment and intervention.

PMID- 8756065
TI  - Pediatric TB in the 1990s.

PMID- 8756067
TI  - What happens to the offspring of diabetic pregnancies?

PMID- 8756068
TI  - Guidelines for assessing HIV in women.

PMID- 8756069
TI  - HIV in adolescents.

PMID- 8756070
TI  - Teaching pregnant adolescents to cope with environmental smoke.

PMID- 8756071
TI  - Expanding on HIV infection in women and children.

PMID- 8756072
TI  - Where are the parents?

PMID- 8756073
TI  - AHCPR releases new clinical practice guidelines.

PMID- 8756074
TI  - Free access to electronic AIDS information.

PMID- 8756075
TI  - Anticoagulants during pregnancy.

PMID- 8756076
TI  - Unusual expression of mRNA typical of Philadelphia positive acute lymphoblastic
      leukemia detected in chronic myeloid leukemia.
AB  - The Philadelphia chromosome (Ph) is found in both chronic myeloid leukemia (CML)
      and acute lymphoblastic leukemia (ALL). The Ph translocation, t(9;22)(q34;q11),
      can disrupt the BCR gene on chromosome 22 in one to two areas called the major
      (Mbcr1) and minor (mbcr1) breakpoint cluster regions. In CML the breakpoint has
      been mapped almost exclusively to Mbcr1, whereas in Ph positive ALL both Mbcr1
      and the upstream mbcr1 breakpoints have been described. In this communication we
      describe an unusual patient with typical chronic phase Ph positive CML and
      evidence of the uncharacteristic mbcr1 breakpoint, predicting expression of the
      ALL-type p190 fusion protein. Fluorescence in situ hybridization demonstrated BCR
      gene rearrangement, the reverse transcription polymerase chain reaction detected
      the BCR-ABL fusion mRNA characteristic of the mbcr1 breakpoint, and failed to
      detect BCR-ABL mRNA characteristic of the Mbcr1 breakpoint. Southern blot
      analysis revealed no rearrangement in Mbcr1, and direct sequencing of the PCR
      product confirmed it to be the ALL-type mbcr1 fusion mRNA with the first exon of
      the BCR gene fused to ABL exon a2. This case differs from the previously reported
      cases of "p190" CML in that the patient presented without abnormal hematopoietic
      features other than those found in typical CML and provides further evidence that
      the p190 mRNA is not sufficient to cause an acute rather than chronic leukemia.

PMID- 8756077
TI  - Effects of density and of dehydration of sickle cells on their adhesion to
      cultured endothelial cells.
AB  - Abnormal adhesion of sickle cells to vascular endothelium may be a factor in the
      initiation of painful vaso-occlusive crisis. The sickle cell population contains
      an unusually large number of less dense reticulocytes that are known to be more
      adhesive than mature red cells, but there is contradictory evidence regarding the
      adhesiveness of dense sickle cells. We used a flow-based assay of adhesion to
      cultured human umbilical vein endothelial cells to test the properties of density
      fractions of sickle cells, prepared either by density gradient or by
      centrifugation of packed cells. We also examined the effects of incubating sickle
      cells with or without cyclical deoxygenation on their adhesion. After
      fractionation on a Percoll-isopaque gradient, the less dense 10% (reticulocyte
      rich) cells and the most dense 10% cells adhered in greater number than the
      remainder (by about twofold). However, after centrifugation of packed cells, the
      less dense 10% were again more adhesive than the "middle" cells, but the most
      dense were not. Exposing sickle cells to constituents of the gradient had no
      consistent effect on adhesion, while centrifugal packing induced a degree of
      hemolysis, and tended to reduce adhesiveness of the dense fraction previously
      obtained from a gradient. Incubation in air at 37 degrees C for 15 hr reduced the
      number of reticulocytes and the adhesiveness of less dense sickle cells compared
      to those held at 4 degrees C. On the other hand, incubation at 37 degrees C for
      15 hr with cyclical deoxygenation caused formation of dense cells and increased
      adhesiveness compared to incubation without cyclical deoxygenation. We conclude
      that young, less dense sickle cells are unusually adhesive, but that this
      adhesiveness is reduced during maturation. However, repeated sickling in vivo
      causes formation of an abnormally dense subpopulation of cells which either
      redevelop an increased tendency to adhere to endothelial cells or preserve their
      initial adhesiveness. Both adhesive cell populations may be implicated in
      promoting vascular obstruction.

PMID- 8756078
TI  - Nondeletional alpha-thalassemia: first description of alpha Hph alpha and alpha
      Nco alpha mutations in a Spanish population.
AB  - Several different deletions underlie the molecular basis of alpha-thalassemia.
      The most common alpha-thalassemia determinant in Spain is the rightward deletion
      (-alpha 3.7). To our knowledge, however, no cases of alpha-thalassemia due to
      nondeletional mutations have so far been described in this particular
      Mediterranean area. Here, we report the existence of nondeletional forms of alpha
      thalassemia in ten Spanish families. The alpha 2-globin gene was characterized in
      ten unrelated patients and their relatives only when the presence of deletional
      alpha-thalassemia was ruled out. The alpha 2-globin gene analysis was performed
      using the polymerase chain reaction (PCR) followed by restriction enzyme analysis
      or by allelespecific priming. This allowed the identification of a 5-base pair
      (bp) deletion at the donor site of IVS I (alpha Hph alpha) in 9 cases and the
      alpha 2 initiation codon mutation (alpha Nco alpha) in one case. Although these
      alpha 2-globin gene mutations are found in other mediterranean areas, our results
      demonstrate their presence in the Spanish population and suggest that the alpha
      Hph alpha/alpha alpha genotype is probably the most common nondeletional form of
      alpha-thalassemia in Spain.

PMID- 8756079
TI  - Hematologic profile and lymphocyte subpopulations in hemoglobin SC disease:
      comparison with hemoglobin SS and black controls. The Transfusion Safety Study
      Group.
AB  - Compared with subjects with homozygous SS disease (Hb SS), persons with
      hemoglobin SC (Hb SC) are known to have a more gradual loss of splenic function,
      a lower incidence of bacterial infections, and fewer end-organ failures. We
      studied hematological indices and lymphocyte subpopulations of 27 Hb SC subjects
      and compared them with 173 Hb SS patients and 131 black controls. Hb SC patients
      had higher hemoglobin levels than Hb SS subjects, lower total leukocyte,
      granulocyte, monocyte, and lymphocyte counts. Platelets decreased with age but
      not significantly, instead of increasing as among Hb SS patients. Mononuclear
      cells were generally similar to controls with the exception of CD8+HLA-DR+ counts
      resembling Hb SS. Hematologic changes in Hb SC are limited to moderate
      granulocytosis in children and adults, mild monocytosis in adults, and increased
      activation of just one lymphocyte subset among those measured.

PMID- 8756080
TI  - Granulocytes from chronic myeloid leukemia (CML) patients show differential
      response to different chemoattractants.
AB  - Binding of chemoattractant to polymorphonuclear leukocytes (PMNL) triggers a
      series of events like polymerization of actin and tubulin, orientation of cells,
      chemotaxis, increase in fluid pinocytosis and phagocytosis, and stimulation of
      microbicidal pathways which includes lysosomal degranulation and generation of
      reactive oxygen species. Earlier studies from our laboratory have shown that
      stimulation of chemotaxis, fluid pinocytosis, and actin polymerization of CML
      PMNL in response to a synthetic chemotactic peptide formyl-methionyl-leucyl
      phenylalanine (fMLP) is significantly lower than that in normal PMNL. It is not
      known whether this lower response of CML PMNL to fMLP is a global phenomenon
      involving different chemoattractant receptors or is restricted to the fMLP
      pathway. We have evaluated chemoattractant induced degranulation process in
      normal and CML PMNL to fMLP, platelet activating factor (PAF), leukotriene B4
      (LTB4), and an analogue of fMLP viz formyl-methionine-1 aminocyclooctane 1
      carboxylic acid-phenylalanine-O-methionine (FACC8) using release of lysozyme as a
      parameter. We find that after stimulation with fMLP and FACC8, the mean percent
      release of lysozyme was significantly lower in CML PMNL as compared to that in
      normal cells (P < 0.001). There was no significant difference between the two
      after stimulation with PAF and LTB4. The results indicate that the fMLP pathway
      is suppressed in CML granulocytes whereas PAF and LTB4 pathways appear unaltered
      in these cells. We therefore also studied the kinetics of peptide-receptor
      interaction with a labelled hexapeptide fNLPNTL which binds to the fMLP receptor.
      Our results show that the number of fMLP receptors/cell is significantly lower in
      CML PMNL (P < 0.05) than in normal PMNL, while their affinity constants and
      dissociation constants were comparable.

PMID- 8756081
TI  - Plasma tissue factor and tissue factor pathway inhibitor levels in patients with
      disseminated intravascular coagulation.
AB  - We measured the plasma levels of tissue factor (TF) and tissue factor pathway
      inhibitor (TFPI) in patients with disseminated intravascular coagulation (DIC) to
      examine the relationship between TFPI and vascular endothelial cell injury.
      Plasma TF (273 +/- 90 pg/ml) and TFPI (252 +/- 125 ng/ml) levels were
      significantly increased in patients with DIC compared with non-DIC patients.
      Plasma TF antigen level was significantly increased in pre-DIC patients (285 +/-
      85 pg/ml), while the plasma TFPI level (152 +/- 54 ng/ml) was not markedly
      increased in such a state. The plasma TF/TFPI ratio was high in the pre-DIC
      patients (2.10 +/- 0.90), and low in the DIC patients (1.40 +/- 0.87) and healthy
      volunteers (0.84 +/- 0.26). There was no significant difference between the DIC
      patients with a good outcome and those with a poor outcome in terms of plasma TF
      levels, although the plasma TFPI level in the DIC patients with a good outcome
      (289 +/- 133 ng/ml) was significantly higher than that in those with a poor
      outcome (187 +/- 75 ng/ml). During the clinical course of DIC, plasma TF antigen
      was increased first, and an increase of the plasma TFPI level followed the
      increase in plasma TF level. These findings suggest that plasma TFPI is released
      from vascular endothelial cells and it may reflect vascular endothelial cell
      injury. It is conceivable that TF and TFPI may play an important role in the
      onset of DIC.

PMID- 8756082
TI  - Detection of T-cell receptor delta gene rearrangement in T-cell malignancies by
      clonal specific polymerase chain reaction and its application to detect minimal
      residual disease.
AB  - A clonal-specific polymerase chain reaction technique to detect T-cell receptor
      delta gene rearrangement in acute lymphoblastic leukaemia (ALL) and non-Hodgkin's
      lymphoma (NHL) was evaluated. It was applied to detect minimal residual disease.
      A sensitive and specific technique to detect minimal residual disease for T-cell
      malignancies was explored. Southern analysis and polymerase chain reaction (PCR)
      were used to detect the rearranged V-D-J segment of T-cell receptor delta (TCR
      delta) gene from malignant cell specimens of patients with leukemia and lymphoma
      of T-cell lineage. The PCR product was sequenced and from the DNA sequences of
      the V-D-J region, a 3' anti-sense primer was designed and synthesized for clonal
      specific PCR (CS-PCR). T-cell receptor delta (TCR-delta) gene rearrangement was
      studied in 40 cases of acute leukaemia and lymphoma of T-cell lineage at
      diagnosis. Using Southern analysis, the positive rates were 28 and 32% for the 18
      T-lymphoma and 22 T-ALL, respectively. A one stage Polymerase Chain Reaction
      (PCR) technique was used to detect the rearrangement in Southern positive cases
      and the PCR positive rates were 80 and 86%, respectively. The PCR technique had a
      sensitivity of 0.1%. Serial follow-up marrow specimens were available from 4 T
      ALL patients following chemotherapy for monitoring of minimal residual disease.
      Their PCR products were DNA sequenced. A 3' primer was designed for each case for
      a clonal specific (CS) PCR. The technique had a sensitivity of 0.003%. It was
      applied to detect minimal residual disease in serial follow-up marrow samples.
      The first patient had persistent negative CS-PCR results and enjoyed continuous
      remission for more than 3 years. The second patient with negative one stage PCR
      but positive CS-PCR results had eventual relapse of leukaemia. The other two
      patients never achieved a morphological remission. These preliminary results
      appeared to support the usefulness of these PCR techniques in detecting minimal
      residual disease and predicting relapses for ALL. However, further clinical
      correlation in larger populations of patients is necessary.

PMID- 8756083
TI  - Possible role of tumor necrosis factor-alpha in erythropoietic suppression by
      endotoxin and granulocyte/macrophage colony-stimulating factor.
AB  - Injection of bacterial endotoxin or granulocyte/macrophage colony-stimulating
      factor (GM-CSF) into exhypoxic polycythemic mice simultaneously with
      erythropoietin (EPO) suppressed erythroid cell formation, as monitored by 59Fe
      incorporation into circulating red blood cells. This effect was dose-dependent
      and time-dependent. GM-CSF did not inhibit erythroid cell formation directly, as
      the antibody to the GM-CSF did not neutralize the effect of endotoxin, the
      inducer of GM-CSF. The suppression of both agents could be partially corrected by
      prior injection of a monoclonal antibody to tumor necrosis factor alpha (anti-TNF
      alpha). These results indicate that the suppression of EPO-induced erythroid cell
      formation by endotoxin and GM-CSF was due in part to the production of TNF alpha.

PMID- 8756084
TI  - Avascular necrosis of bone after adult acute lymphocytic leukemia treatment with
      methotrexate, vincristine, L-asparaginase, and dexamethasone (MOAD).
AB  - Four of 55 (7%) adult acute lymphocytic leukemia patients, age 27-58 years, who
      were treated with methotrexate, vincristine, L-asparaginase, and dexamethasone
      (MOAD) developed avascular necrosis (AVN) of one or both femoral heads 16-39
      months after beginning treatment. All patients were treated with total joint
      replacement without compromise of quality of life during more than 3-9 years of
      follow-up, and they have remained in complete remission for a total of 6.5 + to
      10.5 + years. A review of the literature revealed 11 previously reported cases of
      AVN of bone in patients with acute lymphocytic leukemia, 10 of whom received
      dexamethasone. The patients in the present report received a total dexamethasone
      dose equivalent to that of prednisone, 3.4-5.0 g/M2. Although AVN of bone has
      been reported in patients receiving chemotherapy without corticosteroids,
      corticosteroids appear to be the most common class of agents associated with its
      development, and dexamethasone treatment may be more likely to result in AVN of
      bone than other corticosteroids, for unknown reasons.

PMID- 8756085
TI  - Beta-globin gene haplotype in Hb SC disease.
AB  - We asked the question, is the haplotype found with the sickle hemoglobin gene
      associated with different hematological characteristics in patients who were
      combined heterozygotes for sickle hemoglobin and hemoglobin C (Hb SC disease)? In
      73 adults with Hb SC disease, a Benin haplotype chromosome was present in 56%,
      and Bantu (or Central African Republic; CAR), Senegal, and atypical haplotype
      chromosomes were found in 25%, 6%, and 12%, respectively. No significant
      difference were found in hematological characteristics or fetal hemoglobin levels
      of patients with Benin/C, CAR/C, Senegal/C, and atypical/C haplotypes. There were
      71% C I, 18% C II, and 11% other beta(c) haplotypes. Fetal hemoglobin levels are
      lower in Hb SC disease than in sickle-cell anemia. Perhaps because haplotype has
      no discernible effect on fetal hemoglobin level in Hb SC disease, it does not
      modulate its hematological features.

PMID- 8756086
TI  - Soluble transferrin receptor in the study of fetal erythropoietic activity.
AB  - In order to evaluate fetal erythropoiesis we measured red blood cells,
      hemoglobin, hematocrit, serum transferrin receptor (sTfR), and iron status
      parameters in fetuses undergoing percutaneous umbilical blood sampling, and in
      normal newborns at term. We found high levels of sTfR in fetuses and newborns as
      compared with normal adults (3,149 +/- 181 vs. 1,881 +/- 137 ng/ml, P < 0.00001).
      Concentrations of sTfR correlate with gestational age and red blood cell numbers
      (r = 0.441, P < 0.001; r = 0.366, P = 0.06). sTfR concentrations do not show
      correlation with iron status parameters. The increased sTfR concentration is
      consistent with the fact that fetal life is characterized by cell proliferation
      and tissue growth. sTfR concentration correlates with gestational age and numbers
      of red blood cells, and can therefore be considered a good indicator of fetal
      erythropoiesis. It is conceivable that, during intrauterine life, sTfR expression
      is independent from iron status. sTfR determination will help in reaching a
      better understanding of some aspects of fetal physiology, and will help elucidate
      the physiopathology of fetal hematological diseases.

PMID- 8756087
TI  - Red blood cell alloimmunization in sickle cell disease: the influence of racial
      and antigenic pattern differences between donors and recipients in Brazil.
AB  - Red blood cell (RBC) transfusions are widely used in the management of patients
      with sickle cell disease (SCD). However, repeated RBC transfusions are often
      complicated by RBC alloimmunization. To investigate whether the frequency of RBC
      alloimmunization could be accounted for by racial and RBC phenotype differences
      between donors and recipients in Brazil, in this study we compared the RBC
      phenotype of 100 SCD patients with that observed in 120 randomly selected blood
      donors. A comparison of the RBC phenotype between the two groups revealed a
      statistically significant increase in the frequency of the C antigen in the donor
      population (P < 0.01), but no significant difference was observed for the
      A,B,D,c,E,e,K,k,Fya,M,N,S,s, and Jka antigens. Using standard techniques
      (indirect antiglobulin test, enzyme treatment, and low-ionic-strength solution)
      we observed an RBC alloimmunization rate of 12.9% (11/85) in the SCD patients.
      Fifteen alloantibodies were detected in 11 patients, and most (80%) involved
      antigens in the Rhesus and Kell systems. This observed RBC alloimmunization rate
      in SCD patients in Brazil is lower than that reported by studies from North
      America, suggesting that the requirement for extended antigen-matched RBC
      transfusion for SCD patients in the setting of a RBC phenotype concordant donor
      recipient population may not be cost-effective in some countries.

PMID- 8756088
TI  - Hemorrhage from abdominal non-Hodgkin's lymphoma treated successfully by
      emergency transcatheter arterial embolization.
AB  - A 49-year-old Japanese woman with follicular lymphoma who presented with severe
      abdominal and back pain is reported. She was known to have malignant lymphoma and
      had been previously treated with combination chemotherapy. An abdominal tumor
      occurring at the root of the mesentery and involving the superior mesenteric
      artery (SMA) had been diagnosed by computed tomography (CT), magnetic resonance
      imaging, and abdominal angiography. Emergent ultrasonography and CT findings
      showed intraperitoneal bleeding from the abdominal tumor. Selective SMA
      angiography revealed extravasation from a small branch originating from the
      dorsal pancreatic artery, which was embolized through a catheter by using
      platinum coils. It should be noted that a large tumor of malignant lymphoma,
      involving large vessels, may bleed, and in such a case selective transcatheter
      arterial embolization may be one of the effective modalities for hemostasis.

PMID- 8756089
TI  - Posttransfusion purpura: two unusual cases and a literature review.

PMID- 8756090
TI  - Lymphoblastic transformation of chronic myelomonocytic leukemia in an infant.
AB  - A 10-month-old infant with chronic myelomonocytic leukemia (CMML) of 5 months'
      duration, who had been treated only with transfusion, displayed leukemic
      transformation characterized by lymphoid morphology, PAS positivity, and
      myeloperoxidase negativity. Surface marker analysis of blast cells revealed
      expression of lymphoid-associated antigens (CD10 and CD19) but not myeloid
      associated antigens (CD13, CD14, and CD33). These findings suggest that some
      cases of infantile CMML are clonal disorders arising in a pluripotent stem cell
      that can also differentiate along the lymphoid cell lineage.

PMID- 8756091
TI  - Thrombotic thrombocytopenic purpura and relapses: why do case series differ? The
      Italian Cooperative Group for TTP.
AB  - We examined the retrospective case series of the Italian Cooperative Group to
      determine the incidence of relapses in TTP patients. Of 60 patients who have
      crossed the 10-year threshold from the first episode, only 9 (15%) relapsed
      during that period, a figure far lower than that reported recently. Such
      difference is hardly explainable on the basis of our current knowledge of the
      biological behaviour of TTP. Furthermore, we unsuccessfully analyzed the
      treatment performed in each of our relapsed patients, in search of some element
      that could retrospectively predict the subsequent relapse.

PMID- 8756092
TI  - Risk of monoclonal gammopathy of undetermined significance: a case-referent
      study.
AB  - A retrospective study was conducted in 285 cases of monoclonal gammopathy of
      undetermined significance (MGUS) and in 570 sex- and age-matched hospital
      controls in order to investigate the possible association between socioeconomic
      status, residence, alcohol and tobacco habits, occupation, occupational exposure
      to toxic substances, chronic antigenic stimulation, and risk of MGUS. Significant
      associations with the risk of MGUS were found for farmers (P < 0.005) and for
      workers in industry (P < 0.025). Occupational exposure to asbestos, fertilizers,
      mineral oils and petroleum, paints and related products, pesticides, and
      radiation was significantly (P < 0.05) associated with an increase in risk of
      MGUS. Chronic immune-stimulating conditions, when considered as a group,
      presented a significant (P < 0.025) association with the risk of MGUS, but no
      specific disease has been found to be significantly associated. These data are in
      agreement with the previous reports on multiple myeloma, suggesting that these
      factors may play an important role in the development of monoclonal gammopathies.
      However, these findings need to be confirmed in prospective larger population
      based studies.

PMID- 8756093
TI  - An indolent type of Epstein-Barr virus-associated T-cell-rich B-cell lymphoma of
      the skin: report of a case.
AB  - A 74-year-old Japanese man presented with systemic lymphadenopathy,
      hepatosplenomegaly, and erythroderma in December 1991. A characteristic pattern
      of anti-EBV antibodies was suggestive of latent EBV infection. A skin tumor
      biopsied in April 1993 contained biclonal EBV genomes diffusely in the infiltrate
      of polyclonal T cells and monoclonal B cells. The clinical course was rather mild
      in contrast to that of classical EBV-associated disorders. Our case was
      considered a rare indolent type of EBV-associated T-cell-rich B-cell lymphoma of
      the skin.

PMID- 8756094
TI  - Aberrant CD2 expression in precursor-B acute lymphoblastic leukemia of childhood.
AB  - Aberrant CD2 expression in childhood precursor-B ALL is rare and has recently
      been reported with an incidence of 3.6% in a study by Cantu-Rajnoldi et al.
      [Haematologica 77:384, 1992]. There was no association of the CD2 co-expression
      with other known prognostic factors. Our study represents the second one in the
      literature. Out of 60 childhood acute lymphoblastic leukemias, analyzed
      morphologically and by flow cytometric immunophenotyping, 49 were of precursor B
      origin. Of these 49 cases, CD2 co-expression was detected in 2, yielding an
      incidence of 4.1%. The complete immunophenotypic profiles of these two cases were
      as follows, respectively: (1) CD19+, CD20-, CD24+, CD10+, sig-, CD2+, CD3-, CD5-,
      CD7-, CD13-, CD33-, CD34+, Tdt+; and (2) CD19+, CD20-, CD24+, CD10+, sig-, CD2+,
      CD3-, CD5-, CD7-, CD13+, CD33-, CD34+, Tdt+. Cytogenetic analysis revealed a
      normal male chromosome pattern in case 1 and an abnormal female chromosome
      pattern [4 cells: 46, XX, del (6q) (q21 q23) and 9 cells: 46, XX, del (11q) (q14
      q23)] in case 2. Both patients were in continuous complete remission at last
      follow-up.

PMID- 8756095
TI  - Elevated levels of soluble ICAM-1 in serum of patients with acute myeloid
      leukemia undergoing bone marrow transplantation.
AB  - Serum soluble ICAM-1 concentrations were measured in 10 patients with or without
      chronic graft-vs.-host disease (GVHD) after allogeneic bone marrow
      transplantation. The serum soluble ICAM-1 levels in the patients with chronic
      GVHD were significantly higher than that in the patients without chronic GVHD.
      The data indicated that serum soluble ICAM-1 is a useful parameter for predicting
      chronic GVHD.

PMID- 8756096
TI  - Use of plasma exchange in hereditary deficiency of factor V and factor VIII.
AB  - Combined hereditary deficiency of coagulation factors V and VIII is a very rare
      bleeding disorder. The severity of bleeding is determined by the level of these
      factors, although in general, this is less striking than the severe deficiency of
      either factor alone. We describe in this article a patient with this congenital
      defect, and the preoperative management for major surgery.

PMID- 8756097
TI  - Natural leukocyte interferon-alpha therapy in patients with chronic granulocytic
      leukemia who have antibody-mediated resistance to treatment with recombinant
      interferon-alpha.
AB  - Two patients with chronic-phase chronic granulocytic leukemia initially responded
      to recombinant interferon alpha-2a (rIFN-alpha-2a) but relapsed as a result of
      development of hightiter neutralizing antibodies to rIFN-alpha-2a. Both patients
      were subsequently treated with natural leukocyte IFN-alpha (IFN-alpha-n3), and
      one of the two patients achieved a durable second hematologic and cytogenetic
      remission. IFN-alpha-n3 may be considered for patients in whom antibody-mediated
      resistance to rIFN-alpha-2a develops.

PMID- 8756098
TI  - Implications of prominent cytologic dysplasia persisting in the marrow of a
      patient with CML even after the spontaneous disappearance of the Philadelphia
      chromosome.

PMID- 8756099
TI  - Antiphospholipid syndrome: a case demonstrating diagnostic challenge.

PMID- 8756100
TI  - An "all-oral" combination therapy in chronic lymphocytic leukemia including the
      oral idarubicin.

PMID- 8756101
TI  - In vivo CAMPATH-1 monoclonal antibodies: a novel mode of therapy for acute graft
      versus-host disease.

PMID- 8756102
TI  - Congenital afibrinogenemia: treatment of excessive menstrual bleeding with
      continuous oral contraceptive.

PMID- 8756103
TI  - Hepatitis C virus infection in Waldenstrom's macroglobulinemia.

PMID- 8756104
TI  - Fanconi aplastic anemia associated with beta-thalassemia trait.

PMID- 8756105
TI  - Circulating leukocytes with ingested mucin in a child with Hirschsprung's
      disease.

PMID- 8756106
TI  - Hemolytic anemia precipitated by pregnancy in a patient with hereditary
      elliptocytosis.

PMID- 8756107
TI  - Acquired central diabetes insipidus complicating acute megakaryocytic leukemia.

PMID- 8756108
TI  - The health of youth. A cross-national survey.

PMID- 8756109
TI  - [Recommendations for treatment of asthma in pregnancy].

PMID- 8756110
TI  - [Chronic transfusion hepatitis--an underestimated disease].
AB  - BACKGROUND: The 12th Deutsche Bundestag constituted a fact-finding committee to
      investigate infections transmitted by blood and blood products. 1,358 patients,
      infected with HIV, mostly suffering from hemophilia were registered. Transfusion
      associated hepatitis was not recorded. METHODS AND RESULTS: In a general
      hospital, a prospective study during 12 months revealed that chronic hepatitis C
      was associated in 43% with previous transfusion of blood whereas no case of HIV
      infection, transmitted by blood or blood products was observed (p < 0.01). The
      frequency of blood transfusion in patients without chronic hepatitis and without
      AIDS was 18.5%, also significantly different from patients with chronic hepatitis
      C (p < 0.025). CONCLUSION: Frequency and impact of chronic transfusion hepatitis
      C is underestimated.

PMID- 8756111
TI  - [Renal artery dilatation in renovascular hypertension. Acute and long-term
      outcome in a large patient sample].
AB  - BACKGROUND: Renal angioplasty is an established therapy for treatment of
      renovascular hypertension. This study was performed to evaluate short- and long
      term outcome of this procedure up until 3 years afterwards. PATIENTS AND METHODS:
      Altogether, 111 renal artery stenosis in 92 patients were dilated. Among these
      were 31 fibromuscular and 70 arteriosclerotic lesions, 4 transplant artery
      stenosis and 6 occlusions. RESULTS: The primary success rate for dilatation was
      approximately 90%. Serious complications occurred in 5 of the patients including
      2 fatal myocardial infarctions about 2 weeks after the procedure. Restenosis
      (altogether 25%) almost exclusively occurred during the first few months after
      angioplasty (more often in arteriosclerotic lesions than in fibromuscular
      disease). Successful dilatation resulted in better blood pressure control. In
      several patients with preexisting chronic renal failure improvement of renal
      function was observed; in this group, however, restenosis occurred in about 1
      third of the patients. CONCLUSIONS: Renal angioplasty is a suitable method for
      therapy of renovascular hypertension; in patients with preexisting renal failure
      improvement of renal function may ensue. The decision to treat with angioplasty
      must be weighted carefully against other established and also newer methods
      (surgery vs. antihypertensive medication vs. stent implantation) and should be
      reserved for specialized centers.

PMID- 8756112
TI  - [Hepatic encephalopathy, diagnosis and therapy].

PMID- 8756113
TI  - [Long-term ambulatory blood pressure monitoring. II: Evaluation parameters and
      reference ranges].

PMID- 8756114
TI  - [Accumulation of AGE (advanced glycosylation end-products) in the aging process,
      in diabetes mellitus and in chronic renal failure].

PMID- 8756115
TI  - [Conservative treatment concepts for stable angina pectoris in coronary heart
      disease].

PMID- 8756116
TI  - [Nutrition and HIV infection. I: Causes and sequelae of malnutrition].

PMID- 8756117
TI  - [In the future will economists determine our therapy? Comments during the
      European Cardiology Congress].

PMID- 8756118
TI  - [Plasmacytoma in HIV infection].

PMID- 8756119
TI  - [Costs of drug treatment of neurologic diseases: Parkinson disease, dystonia,
      epilepsy].
AB  - AIM: The costs of drug treatment were evaluated for Parkinson's disease, focal
      dystonias and epilepsy. METHODS: Retrospective analysis over a period of 12
      months of 785 patients who visited regularly a neurological out-patient
      department. RESULTS: Drug treatment caused a mean annual expenditure of DM 3,920.
      (US-($) 2590, pounds 1690) for Parkinson's disease (n = 409), DM 3,620.- (US-($)
      2390; pounds 1550) for focal dystonias (n = 140) and DM 660.- (US-($) 435, pounds
      280) for hemifacial spasm (n = 35) per patient.- In Parkinson's disease costs are
      dependent on the extent of the disease, the type involved and the presence or
      absence of motor fluctuations. In Hoehn and Yahr stage I we calculated costs of
      DM 2,230.- (US-($) 1470; pounds 960), in contrast to DM 11,870.- (US-($) 7830;
      pounds 5100) in Hoehn and Yahr stage V. The occurrence of fluctuations in motor
      ability increased annual costs to DM 6,010.- (US-($) 3970, pounds 2580);
      patients' treatment without motor fluctuations was cheaper (DM 2,700.-; US-($)
      1780, pounds 1160).- The annual treatment costs of focal dystonias and facial
      hemispasm varied due to the location of the involuntary movement and the extent
      of symptoms: DM 4,900.- (US-($) 3300; pounds 2100) were calculated for the
      treatment of cervical dystonias, DM 1,480.- (US-($) 930; pounds 600) for the
      treatment of blepharo-spasm (oromandibular dystonia: DM 1,710.-; US-($) 1200;
      pounds 800) and DM 600.- (US-($) 470; pounds 300) for the treatment of facial
      hemispasm.- The drug treatment of epilepsy caused mean costs of DM 1,740.- (US
      ($) 1160; pounds 750) per year. There were marked differences concerning the
      different epileptic syndromes and types of seizure. CONCLUSION: Costs of drug
      treatment varied considerably in the three diseases depending on the course, the
      type and the different forms of the respective disease.

PMID- 8756120
TI  - Amyloid beta-protein and the genetics of Alzheimer's disease.

PMID- 8756121
TI  - Biosynthesis of surfactant protein D. Contributions of conserved NH2-terminal
      cysteine residues and collagen helix formation to assembly and secretion.
AB  - Surfactant protein D (SP-D) is preferentially secreted as dodecamers consisting
      of four collagenous trimers cross-linked by disulfide bonds. In these studies, we
      examined the biosynthesis of wild-type rat SP-D (RrSP-D) and selected mutants by
      stably transfected CHO-K1 cells to determine the roles of a conserved N-linked
      oligosaccharide, the collagen helix, and interchain disulfide bonds in SP-D
      assembly and secretion. The major intracellular form of RrSP-D accumulated in the
      RER as complexes containing up to four trimeric subunits. Disulfide cross-link
      formation and RrSP-D secretion were selectively inhibited by 2,2'-dipyridyl, an
      inhibitor of prolyl and lysyl hydroxylase, and by 2 mM dithiothreitol, but
      unaffected by tunicamycin or elimination of the consensus sequence for
      glycosylation at Asn70. Although mutants with serine substituted for Cys15 and
      Cys20 (RrSP-Dser15/20) are secreted as trimeric subunits, proteins with single
      cysteine substitutions were retained in the cell. Surprisingly, the secretion of
      RrSP-Dser15/20 was unaffected by 2,2'-dipyridyl. These studies strongly suggest
      that the most important and rate-limiting step for the secretion of SP-D involves
      the association of cross-linked trimeric subunits to form dodecamers stabilized
      by specific inter-subunit disulfide cross-links. Interference with collagen helix
      formation prevents secretion by interfering with efficient disulfide cross
      linking of the NH2-terminal domain.

PMID- 8756124
TI  - Medical negligence.

PMID- 8756125
TI  - Community control of health services for Canadian Indians.
AB  - Many countries have a dominant culture and one or more minorities. Can a single
      type of health care therefore meet the needs of diverse populations? The health
      situation among the Indian populations in Canada could be improved by the "health
      transfer" initiative, which is described below.

PMID- 8756126
TI  - Tackling mental illness: roles for old and new disciplines.

PMID- 8756127
TI  - Health promotion for immigrants in Switzerland.
AB  - Migration, especially when it is forced, involves hardships and health needs that
      cannot always be met by the existing local services. An association in Lausanne
      creatively combines preventive, educational and therapeutic activities for asylum
      seekers, refugees and immigrants.

PMID- 8756128
TI  - A village seizes the reins of health care.
AB  - The setting-based approach to health promotion and education has been adopted in
      an Albanian village. The project requires a high degree of self-determination and
      self-help. External support comes from the International Islamic Relief
      Organization. Encouraging progress is being made as villagers acquire a wide
      range of skills, connected not only with the provision of care but also with such
      matters as fund-raising, health education and relations with public and private
      bodies.

PMID- 8756129
TI  - Capabilities of public, voluntary and private dispensaries in basic health
      service provision.
AB  - A study is reported from the coastal region of the United Republic of Tanzania on
      the capabilities of public, voluntary and private dispensaries in the provision
      of peripheral health services. The implications for the future development and
      coordination of the different sectors are discussed.

PMID- 8756130
TI  - Reorienting health care in Africa--can the elite believe in equity?
AB  - Those who have advantages try to hold on to them, but in doing so they often work
      to the disadvantage of everyone, including themselves. Health workers can play a
      key role in correcting some of the misconceptions about health produced by a
      combination of elitism and the unscrupulous marketing of health products.

PMID- 8756131
TI  - General practitioners for the new age.

PMID- 8756132
TI  - Doctors for the rural poor.

PMID- 8756133
TI  - Hands-on training in health district management.

PMID- 8756134
TI  - For better data, better utilized.
AB  - In Nigeria a training programme was devised whereby staff from health centres
      could appreciate the value of reliable data as a means of raising the standard of
      services. A process of learning by doing enabled the participants to turn routine
      data into tools for management and the improvement of service quality.

PMID- 8756135
TI  - Health information for the grass roots.
AB  - In its endeavours to achieve the health-for-all goals, Sierra Leone confronts
      many formidable obstacles, among the greatest of which are illiteracy and
      poverty. Nevertheless, determined efforts are being made to disseminate health
      messages, including advice on self-help in the prevention of diseases and
      accidents and in tackling illness and disability.

PMID- 8756136
TI  - Sexual hazards for migrant workers.
AB  - In Thailand the incidence of HIV/AIDS, other sexually transmitted diseases, and
      unwanted pregnancies highlights the vulnerability of young people who have moved
      from rural to urban areas as migrant workers. Possible ways of diminishing the
      risks are discussed below.

PMID- 8756137
TI  - Use of indicators in health care management.

PMID- 8756138
TI  - Evaluation of vaccine storage in Turkey.

PMID- 8756139
TI  - Managing very-low-birth-weight babies at home in a rural area.

PMID- 8756140
TI  - In defence of breast pumps.

PMID- 8756141
TI  - Control of urinary schistosomiasis in rural Nigeria.

PMID- 8756142
TI  - Eye care by traditional healers.

PMID- 8756143
TI  - Postgraduate qualification in addictive behaviour: national and international
      perspectives.

PMID- 8756144
TI  - Control of hypertension in Sierra Leone.

PMID- 8756145
TI  - Linkage of health workers' records: example of estimating perinatal mortality
      rates.

PMID- 8756146
TI  - Acute respiratory infections: sentinel survey in Egypt.
AB  - A survey of 115 health centres in five governorates provided morbidity figures
      for acute respiratory infections (ARI) from 75,789 records. The findings give an
      estimate of antibiotic requirements, including dosage forms for young children,
      and help evaluate the performance of individual health centres and the entire ARI
      programme.

PMID- 8756147
TI  - Food safety control: overcoming barriers to wider use of hazard analysis.
AB  - Although appropriate steps can be taken to prevent or reduce risks to health,
      foodborne diseases have continued to present a serious public health challenge.
      The traditional approaches of inspection and end-product testing appear to have
      proved inadequate in tackling the problem and there is an urgent need to apply
      more rational and effective strategies. One such strategy is the Hazard Analysis
      Critical Control Point (HACCP) system.

PMID- 8756148
TI  - [Value of ultrasound in diagnosis of acute appendicitis].
AB  - Acute appendicitis is one of the most frequent causes of an acute abdomen. The
      clinical diagnosis is based on the case history and the physical examination
      which plays a major role in clinical diagnosis. However, in some cases the
      typical clinical symptoms are equivocal or misleading. Without using the
      opportunities of diagnostic imaging the accuracy of preoperative appendix
      diagnosis ranged between 70 and 78%. Consequently the rate of unnecessary
      laporotomies ranged between 22 and 28%. Since 1986, 13 studies including more
      than 5,000 patients have been published showing a sensitivity of 85% and a
      specificity of 96% if the sonographic examination was performed by an experienced
      examiner. The rate of negative laparotomies could be decreased to 7%, and
      possible differential diagnoses could be either confirmed or ruled out by using
      ultrasound technique. Based on the current literature, real-time sonography plays
      a major part in the diagnosis of acute appendicitis.

PMID- 8756149
TI  - [Therapeutic interventions in benign bile duct strictures].
AB  - Surgical treatment of benign bile duct strictures continues to be associated with
      significant lethality. Thus, radiological interventions become increasingly
      important. A total of 32 patients were treated. Their bile duct strictures had
      different origins. We performed percutaneous transhepatic cholangiographies in 32
      patients, cholangioscopies in 7, and biopsies in 2 patients. Therapeutic
      interventions included percutaneous transhepatic drainages in 30 patients, laser
      lithotripsies in 5, and dilatations in 8 patients. As a total, 36 stents (mostly
      Palmaz stents) were implanted in 27 patients. Acuflex stents were implanted in 2
      of these patients and were extracted after successful clearance of the bile ducts
      following stone fragmentation. No severe complications were observed. Five out of
      8 dilatations were unsuccessful, so that stents were implanted. Five patients
      died. Three stent occlusions and 1 spontaneous stent migration occurred after an
      average of 29 months; the latter could be treated by means of radiological
      procedures. The remaining patients are living symptom-free, on average, since
      18.6 months.

PMID- 8756150
TI  - Experience with color-coded duplex sonography after combined kidney/pancreas
      transplantation--preliminary results.
AB  - The value of color-coded duplex sonography in the assessment of combined kidney
      and pancreatic transplantations (KTX/PTX) was studied in 9 patients. In normal
      graft function the median resistive index (RI) was 0.69 (range 0.60-0.80) for the
      kidney and 0.61 (range 0.55-0.70) for the pancreas. Ten episodes of graft
      dysfunction (kidney n = 4; pancreas n = 6) were observed. During renal rejection
      and hemolytic uremic syndrome the RI was above 0.80. In pancreatic rejection the
      RI exceeded 0.80 while all other causes of pancreatic dysfunction were not
      associated with changes in the RI. Color-coded duplex sonography may prove to be
      a reliable noninvasive diagnostic method in the evaluation of the posttransplant
      course after combined KTX/PTX, in particular in the diagnosis of pancreatic
      rejection.

PMID- 8756151
TI  - [Contrast medium assisted dynamic MR-mammography after diagnostic and therapeutic
      interventions on the breast].
AB  - In a retrospective study, the authors evaluated the signal behavior of 150
      patients after intervention in the breast (40 fine-needle biopsies, 10 core
      biopsies, 50 open biopsies, 50 tumor-ectomies with additional irradiation
      therapy). The MR imaging was performed on 1.5-Tesla whole-body scanners using T1
      WI GRE sequences in 2D FLASH technique before and 5 times after i.v. application
      of 0.1 mmol gadopentetate-dimeglumine per kg body weight. There was no signal
      enhancement after fine-needle biopsy. Hematoma due to core biopsy caused signal
      increase in every 5th patient. Enhancement after open biopsy was no more visible
      6 months postoperatively. 12 months after tumorectomy and radiation therapy, most
      patients showed no more signal enhancement. In conclusion, MR mammography can be
      performed after fine-needle biopsy without problems. In case of core biopsy,
      hematoma should be excluded by sonography before. MR mammography should not be
      performed within 6 months after open biopsy, or within 12 months after
      tumorectomy and radiation therapy.

PMID- 8756152
TI  - [Dynamic imaging of gastric ulcer healing using the most modern Morph-Software].
AB  - The presentation of gastric ulcer healing taken from video endoscopy as a dynamic
      process could not be realized till now. The documentation of the dynamic healing
      process shattered either on the patient's compliance or on the inconstancy of the
      image cut due to wobbling. The replay should be performed as a time lapse whereby
      the picture disturbances would become an essential part.-Instead of presenting a
      continuous film, instant takes of ulcer healing were processed. A dynamic effect
      was produced by computer-assisted production of intermediate pictures. A video
      was created in which short video sequences in definite time intervals were
      recorded endoscopically. Single stills-so-called original pictures-fitting
      together from each sequence were selected and spliced together. The missing
      intermediate pictures were made with a special computer technique according to
      the mathematical concept of interpolation. With this technique, the dynamic
      documentation of gastric ulcer healing in a 47-year-old male patient was
      performed. The technique enables an almost natural and real observation of ulcer
      healing and promises new physiological and patho-physiological knowledge in
      gastroenterologic endoscopy.

PMID- 8756153
TI  - Functional MR imaging of anomalies of the aorta.
AB  - Stenosis of a vessel is a well-known reason for increased resistance leading to
      lower flow rates. Other anomalies of the shape or additional blood influx are
      often considered to be less influential on flow dynamics inside the vessel. In
      this report, examples of irregular flow patterns in the human aorta are
      presented. The cases were selected from magnetic resonance examinations of 25
      volunteers and more than 150 patients with dysfunctions of the heart or anomalies
      of the thoracic vessels. The protocol for magnetic resonance examinations
      included black blood imaging performed in the cine mode (with ECG triggering).
      Even minor modifications of the aortic shape are shown to result in marked
      disturbances of the laminar flow pattern in some patients. Effects of abnormal
      curvatures, additional blood influx, stenoses and dilatation of the aorta are
      demonstrated.

PMID- 8756154
TI  - [Differential diagnosis of cervical lymph node enlargements: ultrasound and
      histomorphology of reactive lymph nodes].
AB  - The purpose of this study was to investigate the morphology of reactive lymph
      nodes of the neck in ultrasound and its histological implications. By revealing a
      characteristic sonomorphology of reactive lymph nodes we would like to contribute
      to the differential diagnosis of cervical lymph node enlargements. In 81 patients
      the morphology and the longitudinal/ transverse axis ratio (L/T ratio) of 257
      reactively enlarged lymph nodes were examined. Besides 6 false-positive cases the
      L/T ratio turned out to be a reliable instrument in detecting reactive lymph
      nodes. Concerning the nodal texture, 89 lymph nodes (34.6%) appeared
      homogenously. Those lymph nodes which demonstrated a more complex nodal texture
      could be assigned to three sonomorphological groups: In 134 lymph nodes (52.1%) a
      centrally located echogenoic line ("central echogenoic line', CEL) was observed.
      Its maximal diameter was defined to be maximally up to one third of the lymph
      node width. In the histological examination this CEL could be identified as a
      widened hilus with an increased fibrosis. An echogenoic nodal area measuring
      between one third up to one half of the lymph node width demonstrated
      histologically a fatty replacement of the hilar tissue. This "echogenoic hilus
      reflex' occurred in 28 lymph nodes (10.9%). A nearly complete lipomatous atrophy
      of the lymph node parenchyma was found in 6 lymph nodes (2.4%) demonstrating a
      "central echogenicity' with just a small peripheral, less echogenoic border
      corresponding to the remaining parenchyma.

PMID- 8756156
TI  - Multicentric reticulohistiocytosis. A report of 3 cases and review of literature.
AB  - Multicentric reticulohistiocytosis (MR) is a rare systemic disease of unknown
      cause. The disease is characterized by tissue infiltration of lipid-laden
      histiocytes and multinucleated giant cells. Destructive polyarthritis and skin
      lesions are the most common findings. The disease becomes apparent in adult life.
      We report on 3 patients and discuss the specific radiographic characteristics of
      bone and joint involvement. The radiologic feature is a bilateral, symmetric
      joint involvement with predilection for the interphalangeal and
      metacarpophalangeal joints. In all of our cases we found an early involvement of
      shoulder joints. Erosive arthritis begins at the margins of the joints,
      progressing to osseous defects and to severe joint destruction. In contrast to
      rheumatoid arthritis, periarticular osteoporosis and early joint space loss are
      absent in MR. In addition, significant erosions of distal interphalangeal joints
      are not common in rheumatoid arthritis.

PMID- 8756155
TI  - [Contrast medium behavior of epithelial skin tumors and tumor-like changes in
      high resolution magnetic resonance tomography].
AB  - To evaluate the use of Gd-DTPA in imaging epithelial skin tumors and tumor-like
      lesions, 29 benign, 8 malignant and 4 semimalignant skin tumors were
      prospectively examined by high-resolution MRI at 1.5 Tesla using a 2.5-cm surface
      coil. For tumor assessment, transverse plain and contrast-enhanced scans (0.1
      mmol Gd-DTPA/kg body mass) were performed (TR 500 ms, TE 25 ms, 3 acquisitions,
      256 x 256 matrix, FOV 2.5 cm). Contrast enhancement was quantitively determined
      as the percent enhancement of signal intensity. Histologic findings were
      correlated using the Mann-Whitney-test (p < 0.05). Quality of contrast
      enhancement was independently assessed by three investigators, who mostly
      described inhomogeneous enhancement, regardless of histologic findings. Malignant
      tumors could not be differentiated from benign lesions by contrast enhancement.
      MRI using Gd-DTPA does not provide differentiation of skin tumor types.

PMID- 8756157
TI  - [Diagnostic error of thrombosis of the inferior vena cava with contrast-CT in
      tricuspid valve insufficiency].
AB  - Sonographic evidence of a cystic adrenal tumour was found in a 73-year-old female
      patient with a 6-month history of chest pain and dyspnoea. A computed tomogram of
      the abdomen revealed, in addition to the 5-cm lesion, a contrast medium-free area
      in the vena cava inferior, leading to an initial diagnosis of recurrent pulmonary
      emboli due to a thrombosis of the vena cava inferior. Further diagnostic
      procedures excluded emboli and indicated a dilating cardiomyopathy with mitral
      and tricuspid regurgitation. The contrast medium-free area in the vena cava
      inferior was caused by the influx and regurgitation of contrast medium-free blood
      from the renal and hepatic veins in addition to blood from the right atrium due
      to the tricuspid valve regurgitation. A thrombosis was excluded by means of a
      color-duplex investigation. The patient declined any further diagnostic
      procedures concerning the lesion.

PMID- 8756158
TI  - AAEM case report #13: diabetic amyotrophy.
AB  - A case fulfilling the criteria for the diagnosis of diabetic amyotrophy is
      reported. Based on the clinical and electrodiagnostic features, it is concluded
      that diabetic amyotrophy is a recognizable clinical entity that can be
      differentiated from other diabetic neuropathies. The site of the lesion and the
      pathogenesis in diabetic amyotrophy remain controversial. The course of the
      illness is variable with gradual, but often incomplete, improvement.

PMID- 8756159
TI  - Functional abnormalities in P0-deficient mice resemble human hereditary
      neuropathies linked to P0 gene mutations.
AB  - Mutations in the gene encoding the transmembranous cell adhesion molecule, myelin
      protein zero (P0), have been reported in patients with Charcot-Marie-Tooth
      disease types 1B and 3 (Dejerine-Sottas disease). We have previously shown that
      the targeted deletion of the P0 gene in mice results in impairment of sciatic
      nerve conduction, and we now extend our detailed electrophysiologic investigation
      to the facial nerve. In concordance with histologic investigations which revealed
      severe hypomyelination in peripheral nerves we found the typical
      electrophysiologic signs of severe dysmyelination in both the facial and sciatic
      nerves in mice homozygously deficient for the expression of P0 (P0 -/- mice). As
      compared to control mice (P0+/+), nerve conduction velocities were reduced to
      below 10% and compound muscle action potential (CMAP) amplitudes to below 25%,
      while CMAP duration and excitation thresholds were markedly increased.
      Surprisingly, nerve conduction changes in mice heterozygously deficient for P0
      (P0+/-) were only mild, were detected only in the sciatic nerve, and occurred not
      before 5-7 months of age. They were more prominent at age 12-13 months. Thus, P0 
      /- mice resemble severe human inherited neuropathies like Charcot-Marie-Tooth
      disease type 3 (Dejerine-Sottas disease) with onset early in life, whereas the P0
      +/- mice may resemble the milder form, CMT1B.

PMID- 8756160
TI  - Cortical and spinal mechanisms of facilitation to brain stimulation.
AB  - Compound muscle action potentials (CMAPs) evoked by magnetic brain stimuli are
      larger if the subject provides a steady background voluntary contraction of the
      target muscle. This facilitation could be due either to cortical or spinal
      mechanisms, or both. Both magnetic and electrical stimuli given immediately after
      the onset of a ballistic contraction also evoke markedly facilitated CMAPs. By
      contrast, responses some 200 ms after the onset of such a contraction are
      facilitated if stimuli are magnetic but not if they are electrical. This second
      phase of facilitation is largely cortical in origin. By comparing the size of
      CMAPs evoked by magnetic stimuli at two different delays after electromyogram
      onset, the total facilitation could be dissected into its spinal and cortical
      components. The relationship between CMAP area in the first dorsal interosseous
      and stimulus intensity was different in the two phases of facilitation,
      suggesting a constant background level of spinal facilitation upon which an
      increasing descending volley operated. In experiments in which ballistic
      contractions at increasing force levels were performed it was found that at low
      force levels, spinal facilitation predominated, but at forces greater than 10%
      maximum there were roughly equal contributions from increased spinal cord and
      cortex excitability.

PMID- 8756161
TI  - Acute effects of intravenous injection of beta-adrenoreceptor- and calcium
      channel at antagonists and agonists in myasthenia gravis.
AB  - The effect of intravenous injection of propranolol, verapamil, terbutaline,
      calcium, and edrophonium on neuromuscular transmission has been studied with
      repetitive nerve stimulation and clinical tests in 10 patients with myasthenia
      gravis (MG). The drugs were given intravenously in doses commonly used in
      clinical practice. Only minor clinical effects were noted except for edrophonium.
      The mean decrement of the deltoid muscle was not significantly changed after
      injection of propranolol (before 31%, 15 min after injection 27%) and verapamil
      (before 29%, 15 min after injection 26%). Terbutaline applied after propranolol
      and calcium applied after verapamil improved the decrement substantially.
      Edrophonium applied after propranolol or verapamil also greatly improved the
      decrement. We conclude that there is no rapid deterioration of neuromuscular
      transmission in patients with moderately severe MG after injections with
      therapeutic doses of propranolol and verapamil. However, we do not know if the
      most severely disabled MG patient could have reacted otherwise. We consider that,
      in cardiovascular emergencies, propranolol and verapamil may be used even in
      severe MG but with resuscitation equipment as well as specific antidotes
      available.

PMID- 8756162
TI  - Motor control after spinal cord injury: assessment using surface EMG.
AB  - The brain motor control assessment (BMCA) protocol is a comprehensive
      multichannel surface EMG recording used to characterize motor control features in
      persons with upper motor neuron dysfunction. Key information is contained in the
      overall temporal pattern of motor unit activity, observed in the EMG (RMS)
      envelope. In paralysis, a rudimentary form of suprasegmental control of tonic and
      phasic reflexes can be demonstrated. EMG patterns evoked by voluntary and passive
      maneuvers and by volitional modulation of reflex responses reveal features of
      motor control not apparent in the clinical examination. Such subclinical findings
      may explain paradoxically different responses in apparently similar SCI subjects,
      and may be used to monitor spontaneous or induced changes. The recording
      protocol, examples of EMG patterns, and their prevalence in 40 spinal cord
      injured (SCI) subjects are presented, and compared with 5 healthy subjects.

PMID- 8756163
TI  - Myosin heavy chain profile of cat soleus following chronic reduced activity or
      inactivity.
AB  - To determine the role that normal neuromuscular activity plays in maintaining the
      myosin heavy chain (MHC) profile of adult cat soleus muscles, the spinal cords of
      4 cats were transected (ST) and 8 cats were spinal isolated (SI) for 6 months.
      Nine nonoperated cats served as controls. Electrophoresis demonstrated that the
      soleus from control cats contained 98% type I, and 2% IIa MHCs. Both ST and SI
      resulted in decreased type I and increased IIa MHC, as well as de novo expression
      of IIb MHC. Immunohistochemistry with MHC-specific antibodies demonstrated that
      the soleus from control cats contained 99% type I, 1% IIa, and < 1% hybrid fibers
      (containing both type I and II MHCs). Following ST there were 67% type I, 17%
      IIa, 3% IIb, and 13% hybrid fibers. After SI, 48% of the fibers were type I, 11%
      were IIa, 1% were IIb, 25% were hybrid, and 15% contained embryonic MHC. Thus,
      normal levels of neuromuscular activity appear to be necessary for maintenance of
      the normal adult MHC profile in some fibers. Complete inactivation results in
      developmental MHC isoform expression in some fibers. Therefore, the dependence of
      a fiber on activity as a source of MHC modulation differs substantially among
      fibers even in a relatively homogeneous muscle.

PMID- 8756164
TI  - Endplate dysfunction in healthy muscle following a period of disuse.
AB  - The objective of this study was to test the hypothesis that muscle disuse can
      result in abnormal neuromuscular transmission. Six healthy volunteers (2 females,
      mean age = 33 years) participated in the study. Cast immobilization of one leg,
      for a period of 4 weeks, was used as a model of disuse; the contralateral leg was
      used as a control. Three testing sessions, consisting of stimulation single fiber
      electromyography of the soleus muscle bilaterally, were done before, immediately
      after, and 4 weeks after cast removal. The main outcome measure was neuromuscular
      jitter, measured as the mean of the consecutive differences (MCD) of single
      muscle fiber potentials. A mean MCD was calculated for each muscle, and the data
      from all subjects was pooled to calculate a sample mean MCD. The control side
      showed good reproducibility of results between testing sessions. The experimental
      side showed a significant increase of the sample mean MCD after casting when
      compared to: preimmobilization values (P < 0.001), and to the control side (P <
      0.001). After 4 weeks of recovery, the sample mean MCD returned to
      preimmobilization values. This study presents evidence that muscle disuse,
      without any neuromuscular disease, can result in a reversible dysfunction of
      neuromuscular transmission.

PMID- 8756165
TI  - External calcium dependence of extensor digitorum longus muscle contractility
      during bupivacaine-induced regeneration.
AB  - The effect of the intramuscular injection of bupivacaine hydrochloride on
      selected morphological characteristics and contractile properties of adult rat
      extensor digitorum longus muscle was studied. Recovery of normal fiber size was
      already present 30 days after bupivacaine injection and at 90 days after
      injection, values of the normalized twitch tension (mN/mg of tissue) and of the
      fatigue index approached those measured in control muscle, whereas the normalized
      tetanic tension remained 57% of control. At 7-30 days postinjection, twitch force
      was decreased by reducing [Ca2+]zero (substituted by Mg2+) or adding Co2+ (5
      mmol/L-1). By contrast potentiation of the twitch was recorded in the presence of
      Cd2+ (2 mmol/L-1). Glycerol treatment only reduced, but did not eliminate
      twitches developed by muscles 7 days after injection. Present results emphasize
      the importance of the recovery process in the loss of the susceptibility of the
      contractile responses to extracellular calcium in bupivacaine-injected muscles.
      These data may be of interest in the evaluation of functional aspects of muscles
      in which injections of viral vector or autologous myoblasts have been performed.

PMID- 8756166
TI  - Slow motor conduction mainly limited to motor root in amyotrophic lateral
      sclerosis.
AB  - Motor conduction velocity is expected to be normal or nearly normal in
      amyotrophic lateral sclerosis (ALS). Some studies have suggested that pathology
      may be present in the proximal axons. Indeed, some investigators have shown a
      decrease in the proximal conduction velocity in ALS by using motor conduction
      velocity measurements and H-reflex and F-response recordings, but they could not
      delineate the precise region of the conduction pathology. In this study, unlike
      the ones carried out previously, the most proximal segment has been studied in 11
      patients with ALS, 13 normal controls, and 5 patients with sequel of
      poliomyelitis (SPM) by recording sensory and motor spinal root potentials. While
      no conduction pathology, H-reflex, or F-response abnormalities were found in ALS
      patients compared to normal subjects, it was shown that conduction velocity
      decreased in the proximal segment of the lower motor neuron of the ventral root.
      Despite motor neuron pathology in SPM, there was no proximal motor conduction
      slowing compared with that in normal subjects.

PMID- 8756168
TI  - Effect of fatiguing maximal voluntary contraction on excitatory and inhibitory
      responses elicited by transcranial magnetic motor cortex stimulation.
AB  - Vertex transcranial magnetic stimulation (TMS) elicited tibialis anterior motor
      evoked potentials (MEPs) and silent periods (SPs) that were recorded during and
      following isometric maximal volitional contraction (MVC). During MVC in 6 healthy
      subjects, MEP amplitudes in the exercised muscle showed an increasing trend from
      an initial value of 4539 +/- 809 muV (mean +/- SE) to 550 +/- 908 muV (P < 0.13)
      while force and EMG decreased (P < 0.01). Also, SP duration increased from 165 +/
      37 ms to 231 +/- 32 ms (P < 0.01). Thus, during a fatiguing MVC both excitatory
      and inhibitory TMS-induced responses increased. TMS delivered during repeated
      brief 10% MVC contractions before and after a fatiguing MVC in 5 subjects, showed
      no change in MEP amplitude but SP duration was prolonged after MVC. This SP
      prolongation was focal to the exercised muscle. Silent periods recorded after
      pyramidal tract stimulation were unchanged following the MVC. These results
      suggest that MEP and SP might have common sources of facilitation during an MVC
      and that inhibitory mechanisms remain focally augmented following a fatiguing
      MVC.

PMID- 8756167
TI  - Neuropathy and mortality in diabetes: influence of pancreas transplantation.
AB  - We collected information on patient status and cause of death for 545 insulin
      dependent diabetic subjects who had cardiorespiratory reflex and nerve conduction
      tests performed to determine if presence and severity of autonomic and somatic
      neuropathy is associated with mortality and if a functioning pancreas
      transplantation (PTx) influences mortality. Follow-up was 12-138 months. Abnormal
      cardiorespiratory reflexes were present in 417 patients and there was abnormal
      nerve conduction in 392 patients. Mortality rates for patients with abnormal
      tests were higher (P < 0.0001) than for patients with normal tests. A total
      neuropathy score that included cardiorespiratory and nerve conduction test scores
      predicted survival better than separate scores. Patients with moderate
      neuropathy, but not those with severe neuropathy, who retained a functioning PTx,
      had longer survival times than patients whose PTx failed in the first 3 months.
      Considering only patients transplanted after 1985, those with moderate neuropathy
      who retained a functioning PTx had even longer survival times than
      nontransplanted patients.

PMID- 8756169
TI  - Depolarization accelerates the decay of K+ contractures in rat skeletal muscle
      fibers.
AB  - The experiments examine the effects of membrane potential on the time course of
      K+ contractures in small bundles of rat soleus and extensor digitorum longus
      (EDL) muscle fibers. Control K+ contractures were induced by exposure to a 200
      mmol/L K+ solution in polarized fibers with a resting membrane potential of -83
      mV (3.5 mmol/L K+), while test contractures were evoked with 200 mmol/L K+ from 
      46 mV, after 5, 10, and 30 min in a 30 mmol/L K+ conditioning solution. The decay
      times of the test K+ contracture in depolarized fibers were faster than those of
      the control K+ contracture in both soleus and EDL. A maximum reduction of 60% in
      the time for the contracture to decay from 90% to 10% was seen in soleus fibers
      after depolarizations lasting 10 min, while a reduction of 45% was seen in the
      decay time of EDL fibers after a 5-min depolarization. The amplitudes of the test
      contractures were 30% less than control after 5-min and 10-min depolarization and
      50% less than control after 30 min. Analysis of the results suggests that the
      kinetics of excitation-contraction coupling may be altered in damaged muscle
      fibers.

PMID- 8756170
TI  - A syndrome of concurrent central and peripheral nervous system involvement due to
      Epstein-Barr virus infection.
AB  - Epstein-Barr virus infection can affect both the central and peripheral nervous
      system. In some patients this occurs concurrently. Two patients are presented
      with encephalopathy and acute quadriparesis with diminished reflexes. Positive
      serology for Epstein-Barr virus was found in both patients. Both patients had a
      cerebrospinal fluid pleocytosis in the setting of progressive weakness.
      Electrophysiologic studies early in the course of their illness demonstrated
      abnormal F-wave latencies with normal distal conduction. Electromyographic
      studies demonstrated prominent spontaneous activity in affected limbs. As both
      the encephalopathy and weakness improved, the electrophysiologic abnormalities
      improved. This presentation is characteristic of acute Epstein-Barr virus
      infection. Pathologic studies in other patients have documented both anterior
      horn cell degeneration and edema as well as cellular infiltration of nerve roots
      which are responsible for the paralysis with diminished reflexes and
      electrophysiologic findings. The prognosis for these patients is generally good.

PMID- 8756171
TI  - Necrotizing inflammatory myopathy associated with localized scleroderma.

PMID- 8756172
TI  - Intracortical facilitation of the muscle response after transcranial magnetic
      double stimulation.

PMID- 8756173
TI  - Extent of motor unit activation in the quadriceps muscles of healthy subjects.

PMID- 8756174
TI  - Long-term effects of finger amputation on stump skin sensibility and digital
      nerve conduction.

PMID- 8756175
TI  - Extensive leukemic cell infiltration into skeletal muscles.

PMID- 8756176
TI  - The influence of the reference electrode on CMAP configuration: leg nerve
      observations and an alternative reference site.

PMID- 8756177
TI  - Can proximal nerve lesions give rise to a "Tinel-like" sign distally?

PMID- 8756178
TI  - Phrenic nerve conduction studies in the intensive care unit.

PMID- 8756179
TI  - Sensory abnormalities in the medial thigh: an electrodiagnostic report of 2
      cases.

PMID- 8756180
TI  - Concurrent myasthenia gravis and chronic inflammatory demyelinating
      polyneuropathy.

PMID- 8756181
TI  - G16 as a universal G protein adapter: implications for agonist screening
      strategies.

PMID- 8756182
TI  - The energetics of ligand binding at catecholamine receptors.
AB  - One of the key events in the actions of agonists and antagonists is their binding
      to receptors. Understanding this event is of interest in terms of understanding
      receptor function but it also has immense practical relevance for the design of
      drugs. If the ligand-binding process could be understood in detail, including the
      nature of the interactions made between ligand and receptor, then this could help
      in the design of more-selective drugs. The interaction of a ligand with its
      receptor is clearly of importance in determining the specificity of ligand action
      but ligand-receptor interaction also initiates the processes of signalling that
      are exhibited in the efficacy of ligand action. Here Philip Strange considers
      these events for catecholamine receptors, concentrating mostly on dopamine
      receptors; where necessary the discussion is widened to include other receptor
      systems.

PMID- 8756183
TI  - The distribution and significance of CNS adrenoceptors examined with in situ
      hybridization.
AB  - Several of the established alpha 1-, alpha 2- and beta-adrenoceptors have now
      been isolated and cloned. The in situ hybridization method has been used to map
      the distribution of many of these adrenoceptors within cells of the CNS. These
      studies add complementary and new information to our knowledge of adrenoceptor
      localization provided previously by radioligand-mediated autoradiography.
      Neuronal cell groups containing one or more mRNAs for seven adrenoceptor subtypes
      throughout the rat CNS have been mapped. In the present review Anthony Nicholas,
      Tomas Hokfelt and Vincent Pieribone will examine these localizations and discuss
      the additional information these maps supply, as well as some implications for
      understanding central noradrenaline and adrenaline systems.

PMID- 8756184
TI  - Tachykinin and kinin receptor antagonists: therapeutic perspectives in allergic
      airway disease.
AB  - The morbidity of allergic airway disease and the number of deaths resulting from
      it have not declined in the past ten years. The multiplicity of mediators
      released in the acute allergic reaction and our limited knowledge of the basic
      mechanisms that drive chronic inflammation have hampered the design of effective
      therapeutic regimens for this type of disease. In this article, Claude Bertrand
      and Pierangelo Geppetti summarize recent studies in which new, potent and
      selective tachykinin and kinin receptor antagonists demonstrate the involvement
      of tachykinins and kinins in airway anaphylaxis, and review how these antagonists
      might be of use in treating allergic asthma and rhinitis.

PMID- 8756185
TI  - Neurochemical changes in cocaine withdrawal.
AB  - Cocaine withdrawal in animals causes a transient increase followed by a long
      lasting decrease in mesolimbic dopamine transporters, dopamine efflux and the
      number of dopamine cells firing spontaneously. Other changes in the nucleus
      accumbens and frontal cortex also suggest alterations in dopamine-receptive
      neurones and circuits. In humans, brain imaging has provided evidence for some
      similar, long-lasting changes in dopaminergic neurones and innervated areas.
      These results suggest a protracted biochemical abstinence syndrome for cocaine.
      In this review, Michael Kuhar and Nancy Pilotte focus on biochemical changes that
      occur following withdrawal from repeated cocaine administration. A key question
      for treatment is whether (some of) these persistent changes underlie withdrawal
      symptomatology such as anhedonia and relapse.

PMID- 8756186
TI  - The stimulatory effects of opioids and their possible role in the development of
      tolerance.
AB  - Opioids have stimulatory as well as the traditional inhibitory effects on
      neurotransmission, but the underlying mechanisms are poorly understood. Here,
      Darren Smart and David Lambert review the stimulatory effects of opioids on
      second messengers, including inositol (1,4,5)-trisphosphate (IP3), protein kinase
      C (PKC), Ca2+, and cAMP, and propose that these coordinated changes at the
      cellular level underlie the facilitatory effects of opioids on neurotransmission.
      The evidence for a possible role for these stimulatory effects, particularly the
      activation of PKC by opioids, in the development of tolerance is also discussed.

PMID- 8756187
TI  - [Ultrasonographic density of amniotic fluid and its correlation with fetal
      pulmonary maturity].
AB  - In order to determine if the amniotic fluid density is correlated with fetal lung
      maturity, we carried out a prospective study in the Hospital de Gineco
      Obstetricia del Centro Medico Leon del Instituto Mexicano del Seguro Social. One
      hundred and forty one patients with pregnancies between 13 and 41 gestation weeks
      were included. The amniotic fluid density was calculated by counting the level of
      echoes (free-floating particles) in the amniotic fluid. We found a significant
      correlation (P < 0.05) between the level of echoes and the gestation age,
      nevertheless, the correlation coefficient was very low (R = 0.28), therefore we
      concluded that this procedure is not a reliable predictor of fetal lung maturity.

PMID- 8756188
TI  - [Ovulation induction with pure FSH in anovulatory patients resistant to clomifene
      citrate].
AB  - The objective was to evaluate the utility of the pure FSH as treatment of women
      clomiphene-resistant. Seventy two patients clomiphene-resistant were treated with
      pure FSH. Ovulation induction was started with 75 IU of pure FSH on day 3 of the
      menstrual cycle, monitoring the follicular growth with transvaginal
      ultrasonography, additional doses of pure FSH were administered accordingly.
      Human chorionic gonadotropin (10,000 IU) was administered when the dominant
      follicle reached a diameter > or = 16 mm. The pregnancy rate per cycle was 18.0%,
      on the other hand, the cumulate rate of pregnancy was 72.2%. There was not
      significant difference in the pregnancy rate between patients with primary or
      secondary infertility. The rate of spontaneous abortions was similar to the
      general population. As conclusion, it therefore appropriate to offer the
      treatment with pure FSH to patients clomiphene-resistance. The cases with
      gonadotropin-resistance, will be candidates to surgical procedures.

PMID- 8756189
TI  - [Cervical pregnancy. Report of a case. Diagnostic and therapeutic
      considerations].
AB  - A patient with cervical pregnancy is reported, in spite of the important bleeding
      a radical management was not required. Clinical, ultrasonographical and
      histopathological criteria which are needed for diagnosis are reviewed. Also some
      management alternatives are discussed.

PMID- 8756190
TI  - [Pregnancy toxemia. Oxygen input/extraction in preeclampsia-eclampsia].
AB  - We tried to determine if the toxemia of pregnancy has during its clinical
      evolution a dependent DO2/VO2 relationship and determine its critical DO2 and
      finally define if this has a prognostic value. There were included patients with
      diagnosis of preeclampsia/eclampsia that were enter at the Intensive Care Unit
      for treatment and monitoring. It was placed a catheter in the pulmonary artery
      and it was determine the cardiac output and by means of standard formulas the
      DO2, VO2 and EO2 were calculated. The critical delivery of oxygen was stablished
      in agree at the Gutierrez's method. At the same time it was monitorised the base
      excess which was gotten from arterial and venous blood gases. 36 patients (29
      with preclampsia and 7 with eclampsia) were included, with a mean age of 26.3
      years old. The mean gestational age was 36.1 weeks. The critical delivery for
      preeclamptic patients was stablished in 924 mL/min and at the eclamptic patients
      in 830 mL/min: both values had prognostic correlation with survival and
      nonsurvival patients (p < 0.001, x2 = 28.29). In survival patients it was a
      dependent DO2/VO2 relationship during the first 72 hours of study and then it was
      independent; this fact was accompaniment of a positive increase in the base
      excess and a decreasing in the EO2 values (< 27%). In the nonsurvival group,
      these mainteined a DO2/VO2 relationship in a dependent way during all the study
      and it was accompaniment with a continuous negative base excess with values of
      EO2 > 30%. The toxemia of pregnancy had a behaviour like state accompaniment of a
      dependent DO2/VO2 relationship causing an important oxygen deficient that was
      improved was improved in the survival patients that reach values over the
      critical delivery. These facts suggesting the presence of a metabolic blockade in
      variable degree that can improve or increase agree a therapeutic manipulations in
      the critic DO2.

PMID- 8756191
TI  - [Pre- and postgestational vaccination].
AB  - Vaccination is one of the most important methods to prevent infectious diseases,
      it consist of application of an inactive but immunogenic antigen, with the
      objective of simulating a natural infection and originate an immunological
      response. Important vaccines used in women's reproductive age are: 1)
      antirubella, if the woman has not serum antibodies against rubella virus; 2)
      tetanus toxoid is indicated in all pregnant women which had not been vaccinated
      against tetanus in the last ten years; 3) hepatitis B vaccine, to be applicated
      in newborns of women with positive serological indicators of chronic hepatitis B
      infection; 4) antirabies vaccine and gamaglobulin hiperimmune must be used in
      women with a recent exposure to rabies virus.

PMID- 8756192
TI  - [Mammary tumor puncture with fine needle].
AB  - Breast cancer is the second malignant tumor that affects women in our population.
      The fine needle biopsy is a sensitive and specific technique. The purpose for
      this study was to show our experience at our institution. The fine needle biopsy
      was performed in 22 patients with diagnosis of breast tumor; all were surgically
      treated. In all the cases the initial cytology showed a high correlation with
      final histology findings. There were no complications. It was concluded that with
      an adequate fine needle biopsy technique, results correlate well with
      histopathologic study, with high sensitivity and specificity. This technique is
      easy to perform, with a low cost, and it may be considered as an useful tool in
      the study of patients with breast tumors.

PMID- 8756193
TI  - [New approaches to the treatment of urinary tract infection].
AB  - A revision of the therapeutic alternatives actually available is carried out for
      the treatment of urinary tract infections in the non pregnant woman. It stands
      out the importance of differentiats between the complicated infections from the
      ones which are not. It is related that indications and results are obtained with
      the administration of one single dose. The causes and diagnoses as well as the
      therapeutic methods are empasized in the cases of persistent or recurrent
      infections.

PMID- 8756194
TI  - [Galanin, a new neuropeptide. Review].
AB  - Galanin is a 29 amino-acid peptide originally isolated from porcine intestine. It
      is synthesized as part of a large precursor peptide the preprogalanin.
      Immunological studies has showed that there is interspecies conservation of the N
      terminal portion although the C-terminal portions has a little of
      immunoreactivity. Galanin has a number of pharmacological properties in whole
      animals and isolated tissues. Galanin contracts isolated preparation from rat
      fundus, ileum, colon and urinary bladder. Direct administration of galanin (pGal)
      into the rat third ventricule stimulates food intake, increases plasma growth
      hormone and prolactin levels and decrease dopamine levels in the median eminence.
      Intravenous infusion in dog and humans induce a hyperglycemia and glucose
      intolerance and inhibits the insulin, somatostatin and pancreatic polipeptide
      secretion from pancreas. Galanin is a estrogen-stimulated peptide. Estrogens
      increase dramatically the synthesis of their mRNA and the peptide in the rat
      pituitary. Galanin-like immunoreactivity is widely distributed in several
      mamalian species including humans. In the central nervous system it was found in
      medium emminence, hypothalamus, arcuate nucleus etc. Its localization in
      neurosecretory granules suggest that galanin functions as a neurotransmitter. The
      detection of a Gal-immunorectivity in the plasma after 17 beta estradiol
      stimulation suggests that galanin has a distal target and therefore, may be an
      additional anterior pituitary hormone. Galanin has been localized in reproductive
      tissues and this suggests that it may play an estrogen mediated role in the
      hypothalamic and pituitary function. However, the molecular mechanisms involved
      in their function remain to be studied.

PMID- 8756195
TI  - [Bladder drainage in patients undergoing the Pereyra surgical procedure].
AB  - Postoperative acute urinary retention was evaluated in the patients who underwent
      Pereyra procedure. Comparison of suprapubic and urethral catheterization. Between
      January 1994 and July 1995, fifty two patients with urinary stress incontinence
      underwent Pereyra procedure, 31 female patient with suprapubic drainage (cistofix
      Ch 15) and 17 urethral catherization with a latex foley catheter. Sponatneous
      micturition and urinary retention was evaluated until the catheter was removed.
      Mean age was 43.8 years (32 a 66), the duration of suprapubic vesical drainage
      with suprapubic catheter were 3 days in 58.6% of the patients, and more than 3
      days in 41.29%. Recatheterizacion in the patients with urethral drainage was more
      frequent. Urinary retention after 7 days was present in 23.99% with suprapubic
      vesical drainage and 28.5% with urethral catheter. Recatheterization is more
      frequent in patients with urethral catheter.

PMID- 8756196
TI  - [Genitourinary fistulae at the National Institute of Perinatology].
AB  - Evaluation of the characteristics of urogenital fistula with a retrospective
      study at the clinic of Urology Ginecologica in the Instituto Nacional de
      Perinatologia between March 1992 to June 1995, information of the location,
      etiopathogenesis of the disease, urinary tract infection and surgical treatment
      were obtained form de patients records in the clinic. The etiophatogenesis of the
      disease was surgical gynecological procedures in 51.1%, and obstetric cause
      48.5%; the location were 14 (66.6%) vesicovaginal, 5 (23.5% 0 ureterovaginal and
      2 (urethrovaginal). The abdominal approach were in 8 patients and vaginal route
      in 9, no surgical treatment were 2. Successfully repair fistula were in 80.9%.
      Urinary tract infections before treatment agreed on the obstetric etiology was
      47.6%, and for surgical gynecological procedures 52.2%. There is an increase in
      the incident of obstetric vesicovaginal fistula, we believe it depends on the
      patients that we have in de Instituto Nacional de Perinatologia, most of them are
      obstetric patients.

PMID- 8756197
TI  - [Obstetrical hysterectomy. Evolution and change].
AB  - We analyze a selected patients group in whom obstetric hysterectomy were
      performed, represented the present orientation for management pregnancy, delivery
      and puerperal complicated. No mortality in this series was observed, but
      morbidity arose 65.21%. This paper maintenance risk shape related age, evolution
      pregnancy, type of complication and change about parity (III-IV more frequency),
      no Cesarean section history and different kind of morbidity. Conclude preventive
      integral management and early indication of Obstetric Hysterectomy with good
      extrafascial technic and indentification difficulties or surgical problems.

PMID- 8756198
TI  - [Gynecology and obstetrics and the health system reform in Mexico].
AB  - Mexican Health System Reformation in Gynecology and Obstetrics is analyzed. The
      last 35 years, the specialty of Gynecology and Obstetrics has had dramatic
      advances which have forced the obstetrician/gynecologist to demand continuing
      medical education on doctrinaire aspects, skills development, epidemiology and
      sociology, as well as technological advances. In Mexico, social-medical field
      decrees a reproductive health program which points: priority to women's health,
      promotion in preventive actions, to consider economic facts and to integrate
      national programs. Finally, there is a reflection on the importance of having
      certified obstetrician/gynecologist.

PMID- 8756199
TI  - [Secondary prevention and cardiac rehabilitation in Spain. Section of Preventive
      Cardiology].
AB  - Secondary prevention and cardiac rehabilitation constitute both a unique strategy
      in the prevention of coronary heart disease. Comprehensive cardiac care must be
      considered one of the main objectives and the Spanish cardiologists dedicate less
      attention to it than to other cardiological procedures. Several international
      recommendations on secondary prevention and cardiac rehabilitation have been
      published during the last years, and both strategies have shown a good cost
      benefit ratio. Several measures for secondary prevention, like reducing
      cholesterol levels in hypercholesterolaemic patients, and the treatment with
      aspirin, have also shown a decrease in CHD mortality and total mortality. Cardiac
      rehabilitation programmes improved some sociolaboral outcomes. In spite of those
      facts, the Spanish cardiologists pay little attention to secondary prevention and
      cardiac rehabilitation, as the results of two recently distributed questionnaires
      show.

PMID- 8756200
TI  - [Pulmonary hypertension: current aspects].
AB  - Primary pulmonary hypertension, although less frequent than secondary forms,
      represents the true paradigm of this disease. The recent investigations on
      pulmonary vascular response mechanisms to different stimuli has increased our
      knowledge about the mechanism of high pulmonary pressure. Molecular biology of
      the endothelial cell has provided evidence that endothelial injury plus a genetic
      individual predisposition may be the pathogenic mainstream of this disease. The
      histologic findings of pulmonary hypertension are still a matter of controversy,
      although the clinical, epidemiological and prognostic features are better
      defined. Therapeutically, there has been important advances, specially with
      various vasodilators, like calciumantagonists, prostacyclin, adenosine and nitric
      oxide, as well as new routes of administration. In more advance stages of the
      disease, atrial septostomy (only paliative) and pulmonary or cardio-pulmonary
      transplantation, are other therapeutic options to consider, after an adequate
      selection of patients.

PMID- 8756201
TI  - [Hypertrophic myocardiopathy with isoelectric T waves].
AB  - INTRODUCTION AND OBJECTIVES: The lack of specificity of electrocardiographic
      (ECG) recording showing isoelectric T-waves often leads to diagnostic doubts.
      This study attempts to demonstrate that asymptomatic patients who demonstrate
      benign forms of hypertrophic cardiomyopathy may be identified from a typical ECG
      pattern showing isoelectric T-waves. METHODS: In 45 out of 5,126 asymptomatic
      healthy aircrew members, an ECG pattern which showed isoelectric T-waves in all
      leads, but were normal in V2 and V3, was found. 12 of them had negative T-waves
      in III and aVF leads. Cardiac echo-Doppler, Bruce test and 24-hour Holter
      recordings were performed in 29 of the 45 cases; all were males aged 30-55 (43.1
      +/- 7.1) without any associated disorder nor engaged in heavy exercise, and a
      control group of 15 healthy subjects. In each of the 29 cases, 2-21 ECG's (11.1
      +/- 6.3) performed over a period of 2 to 20 years (13.0 +/- 5.9) were reviewed.
      RESULTS: In 23 of the 29 cases (79.3%), echo-Doppler criteria of non obstructive
      mild hypertrophic cardiomyopathy were found. T-waves became normal during
      exercise testing, returning to isoelectric during recovery, in 19 of the 23
      cases. In 17 of these cases, reversible T-wave changes were observed between
      successive ECG's; T-wave changes became clearly negative when the level of
      exercise was increased. Holter recordings did not show pathological findings.
      CONCLUSIONS: We believe that echo-Doppler studies must be performed in
      asymptomatic patients showing the ECG pattern described above, because they are
      strongly suspicious of having mild hypertrophic cardiomyopathy.

PMID- 8756202
TI  - [Follow-up of left ventricular systolic function in the first year following
      previous infarction].
AB  - OBJECTIVES: To follow the left ventricular systolic function changes as assessed
      by global and regional ejection fraction during the first year of evolution after
      anterior myocardial infarction, as well as to analyse how the most relevant
      clinical and angio-graphic parameters influence them. MATERIALS AND METHODS:
      Sixty-six consecutive patients with a first infarction of anterior location,
      completed 1 year of follow-up with radionuclide ventriculography, T1-SPECT after
      exercise or dypiridamole and cardiac catheterization before discharge;
      radionuclide ventriculography was repeated 6 and 12 months later. Twenty-five
      patients underwent revascularization procedures at the time of predischarge, 16
      using successful percutaneous angioplasty of the left anterior descending artery
      and 9 using aorto-coronary graft surgery. Dilated patients were controlled, from
      an angiographic point, of view 6 months after PTCA. RESULTS: Predischarge global
      EF (42.9 +/- 12.6) increased significantly between the 6-month (46.9 +/- 12.8; p
      < 0.001) and 12-month (47.6 +/- 12; p < 0.001) studies. Differences in these two
      last studies were minor and had no statistical significance. A significant
      increase was present in revascularized or medically treated patients; i.e. those
      who underwent thrombolytic therapy or conventional treatment at admittance as
      well as mono or multivessel disease patients. No significant differences were
      detected in the mean ejection fraction in patients without residual stenosis in
      the infarct-related artery (48.1 +/- 13.3 vs 50 +/- 12.6; NS) or those presenting
      a pre-discharge ejection fraction > or = 45% (53.5 +/- 7.5 vs 55.1 +/- 3.3; NS).
      Among different variables tested, predischarge global ejection fraction (negative
      coefficient) and, to a lesser extent, percutaneous angioplasty were independent
      predictors of a significant increase of ejection fraction during follow-up.
      Changes from predischarge to 12 month study were significant in the regional
      ejection fraction in the anteroseptal (33.1 +/- 14.7 vs 40.1 +/- 13.3; p <
      0.001), inferoseptal (34.6 +/- 15.8 vs 42 +/- 16.9; p < 0.001), apical (46.3 +/-
      19.1 vs 50.8 +/- 19.7; p < 0.01), antero-medial (50.6 +/- 22.4 vs 56.6 +/- 24.3;
      p < 0.01) and anteroapical (51.6 +/- 23.5 vs 58 +/- 27.5; p < 0.01) segments. In
      the anterobasal segment, regional ejection fraction only showed a statistical
      tendency to increase during follow-up and changes in inferior and lateral
      segments, distal to the infarcted area, were minor and without statistical
      significance. The most distinct infarct-related segments, antero- and
      inferoseptal, showed significant increases in the main group of patients,
      revascularized or nonrevascularized, undergoing thrombolitic or conventional
      therapy, with single or multivessel disease. Only patients without residual
      stenosis of the infarct-related artery (the left descending anterior) disclosed
      negligible or negative changes without statistical significance. Percutaneously
      dilated patients showed the highest increase of the infarct-related segments
      regional ejection fraction. In multivessel disease, the infarct-related segments
      regional ejection fraction did not increase significantly in surgically treated
      patients, conversely to those who underwent medical therapy. CONCLUSIONS: Global
      and regional ejection fraction of the infarcted area increased significantly
      during the first year after anterior myocardial infarction, mainly prior to six
      months patients with significant residual stenosis of the artery related to the
      infarct. Recovery is present both in patients who underwent thrombolysis or
      conventional treatment at admittance and revascularization or medical treatment
      before discharge and is inversely correlated to the predischarge global ejection
      fraction value. This evolution suggests that a significant amount of stunned
      myocardium is still present before discharge.

PMID- 8756203
TI  - [Comparative study of 3 algorithms to localize the accessory pathway in Wolff
      Parkinson-White syndrome].
AB  - BACKGROUND AND OBJECTIVES: Some electrocardiographic algorithms have been
      developed to predict the location of the accessory pathway in the WPW syndrome.
      Few studies address the interobserver variability of such algorithms and the
      possible observer-dependent changes of accuracy. This study analyzes three
      algorithms to localize accessory pathways recently published, comparing the inter
      observer variability, their predictive value and the most frequent problems
      observed during their application. METHODS: Ninety-six electrocardiograms from
      patients who underwent successful ablation of a single accessory pathway were
      reviewed. The location of each pathway was predicted by two independent observers
      according to three different reported electrocardiographic algorithms. The
      interobserver agreement, percentage of correct predictions and critical steps of
      each algorithm were analyzed. RESULTS: The interobserver agreement varied between
      64 and 79% and the accuracy between 38 and 67%. The best results were obtained in
      the left lateral accessory pathways (69 to 89% correctly located). All the
      algorithms presented critical steps at which more than 20% of pathways were
      incorrectly classified. CONCLUSIONS: The analyzed algorithms present a high
      interobserver variability. The accuracy obtained is clearly lower than that
      reported by the corresponding authors. These facts should be considered when
      being used them in clinical settings.

PMID- 8756204
TI  - [Impact of electric cardiac stimulation on ventricular function and the natural
      history of patients with myocardiopathy].
AB  - There has recently been an increasing interest in beneficial effects of cardiac
      pacing in patients with myocardial diseases, especially in Obstructive
      Hypertrophic and Dilated Cardiomyopathy. The experience with dual-chamber pacing
      for obstructive hypertrophic cardiomyopathy is now important. DDD pacing for
      sinus rhythm patients and VVI pacing in patients with atrial fibrillation have
      shown considerable symptomatic improvement, with a significant decrease of
      angina, dyspnea, presyncope and frank syncope. It has been suggested that DDD
      pacing may prevent sudden death and improve survival rates in these patients, but
      this has not yet been established. The experience with DDD pacing in dilated
      cardiomyopathy is more limited, but in specially chosen patients, DDD pacing with
      short AV delay has shown symptomatic improvement and a decrease in the need for
      further hospitalization due to worsening of heart failure. There is no current
      evidence of higher survival rates with this treatment, but DDD pacing may be used
      in patients with end-stage dilated and isquemic cardiomyopathy who are waiting
      for a heart transplantation.

PMID- 8756205
TI  - [Atrial rupture secondary to infarction. Echocardiographic diagnosis].
AB  - A 70 year old male was admitted to the hospital 3 days after suffering one
      episode of ischemic chest pain. On admission he complained of non-productive
      cough, pleuritic pain, cardiomegaly I/IV and sinus tachycardia. Later on, he
      developed frequent auricular prematurities and flutter. The cardiac enzymes were
      elevated confirming the diagnosis of myocardial necrosis. One echocardiogram
      showed an important pericardial effusion. Color Doppler, high flow velocity from
      the lateral wall of the left atrium towards the apex, above the mitral valve. The
      transesophageal echocardiogram clearly showed the presence of a pathological
      communication at this level. One month later, a nodular image compatible with an
      organized thrombus was observed at the same level, sealing the rupture site.

PMID- 8756206
TI  - [Bradycardia and asystolia secondary to epileptic crisis. Report of a case].
AB  - We report the case of a 21 year old man with bradycardia and asystolia after a
      seizure. No cardiac disease could be demonstrated, but electroencephalography
      after sleep deprivation showed the presence of a temporal irritative focus. The
      importance of differential diagnosis between cardiogenic syncope and loss of
      consciousness due to epilepsy is discussed.

PMID- 8756207
TI  - [Acquired aortic coarctation after surgical operation of ductus arteriosus in a
      preterm infant].
AB  - The coarctation of the aorta can be acquired or secondary to the surgical
      correction of congenital anomalies of the great vessels. We report the cases of
      two newborns operated for patency of the ductus arteriosus (normal aortic arch
      and a great left-to-right-shunt). During the postoperative period the patients
      were asymptomatic and the echocardiogram showed no abnormalities. Later, both
      patients developed coarctation of the aorta. This is the first report of this
      condition during the neonatal period.

PMID- 8756208
TI  - [Restrictive cardiac involvement in a patient with dyserythropoietic anemia and
      secondary hemochromatosis].
AB  - We report a case of a 63 year old woman diagnosed with dyserythropoietic anemia
      who was admitted to our hospital with congestive heart failure. Iron's metabolism
      disturbance, CT-Scan and magnetic resonance imaging allowed us to make the
      diagnosis of acquired hemochromatosis due to multiple transfusions. The
      echocardiographic study was compatible with a myocardial restrictive pattern
      caused by iron deposits.

PMID- 8756209
TI  - [Pulmonary artery thrombosis in a patient with mitral-tricuspid valve disease.
      Added value of peroperative transesophageal echocardiogram].
AB  - The performance of peroperative transesophageal echocardiography on a 60 year old
      woman with mitral and tricuspid valve disease discovered a previously undiagnosed
      thrombus in the right pulmonary artery that completely occluded the inferior
      lobar branches. Following valvular surgery, a successful thromboendarterectomy
      was performed.

PMID- 8756210
TI  - [Current and future prospects of molecular biology techniques in the
      epidemiologic study of nosocomial infections].

PMID- 8756211
TI  - [Epidemiological profile of non-typhi salmonellosis in a hospital in urban Madrid
      (1980-1994)].
AB  - BACKGROUND: The aim of this study was to describe the epidemiologic profile of
      non-typhoid salmonellosis at a general hospital in the metropolitan area of
      Madrid. METHODS: A descriptive and retrospective study of non-typhoid
      salmonellosis diagnosed at Microbiology Department of Fundacion Jimenez Diaz from
      May 1980 to December 1994 was done. RESULTS: Non-typhoid Salmonella (NTS) was
      identified in 1796 specimens of 1463 patients, 520 (35.5%) were under 15 years
      and 943 (64.5%) were over 14 years. The infection was intestinal in 1288 (88%)
      cases, bacteremic in 129 (8.8%) and focal in 46 (3.1%). The extraintestinal
      infection was most frequent in patients over 14 years (15.5% versus 5.6%; p <
      0.001). From 1987, 34 adults patients with human immunodeficiency virus (HIV)
      infection developed salmonellosis. The infection was due to Salmonella serogroup
      B (29.4%) and the extraintestinal manifestations (58.8%) were most frequent in
      HIV-infected patients than in the control-group (p = 0.004 and p < 0.001,
      respectively). Salmonella serogroup D was identified in 1041 (71.2%) episodes,
      and serogroup B in 259 (17.7%). Salmonella serogroup B and C were more resistant
      to one or more antibiotics than Salmonella serogroup D (p = 0.001). Resistance of
      NTS (principally Salmonella serogroup B) for one or more antibiotics
      (particularly ampicillin and chloramphenicol) increased significantly during the
      period of study (p < 0.001). CONCLUSIONS: The HIV-infected patients had a
      predisposition to develop extraintestinal Salmonella infections. Resistance of
      NTS for antibiotics, especially Salmonella serogroup B, has significantly
      increased during the last years.

PMID- 8756212
TI  - [Tuberculosis of the otorhinolaryngologic region: laryngeal and extra-laryngeal
      forms].
AB  - BACKGROUND: The aim of the study was to assess all patients with ENT symptoms
      whose histologic and/or microbiologic diagnosis confirmed tuberculosis. METHODS:
      All the anatomopathologic studies performed in the ENT unit in the authors'
      hospital in which the presence of acid-alcohol resistant bacilli were observed.
      All cases of cervical adenitis were not included. RESULTS: Eighteen patients with
      the following localizations were studied: 14 laryngeal tuberculosis and 4 extra
      laryngeal tuberculosis (2 oropharyngeal, 1 otic and 1 sinusal). In the laryngeal
      forms, all patients were male except for one, and all were smokers. The duration
      of the symptoms was greater than 3 months in all the cases. Unilateral cord
      involvement was most commonly found, and in 2 cases this was associated with
      carcinoma of the vocal cord. Twenty-nine percent did not present with coincident
      pulmonary tuberculosis. None of the extra-laryngeal forms showed pulmonary
      involvement. All the patients were women and only 1 was smoker, the
      symptomatology was greater than 3 months in all cases and all required biopsy for
      achieving diagnosis. The evolution with medical treatment was favorable in all
      cases. During the same time period, 2300 cases of pulmonary tuberculosis were
      diagnosed in the authors' hospital. CONCLUSIONS: Tuberculosis of the upper
      respiratory tract is infrequent. Pulmonary involvement is common, although in
      this series this was only found in 71% of all laryngeal forms. Diagnosis is
      difficult, except in cases of coinciding pulmonary involvement and usually
      requires surgery for biopsy. Response to medical treatment is usually good.

PMID- 8756213
TI  - [Incidence and risk factors for nosocomial infections in a neonatology unit].
AB  - OBJECTIVE: Neonatal nosocomial infection is a very important cause of morbidity
      and death in the hospital setting. The aim of our work is to study the incidence
      and risk factors associated with nosocomial infection in a neonatal unit. METHOD:
      We followed 321 patients in a 6-month-long prospective, observational study. As
      units of measurement we used Incidence Density and Accumulative Incidence. For
      the statistical analysis we used chi-square and the logistic regression. RESULTS:
      Nosocomial infection incidence density for the whole neonatal unit was 39.63%
      infections per 100 patients per month, while the accumulative incidence was
      16.19%. Using a logistic regression method, the umbilical cord artery
      catheterization and days of stay variables both showed a statistically
      significant difference with nosocomial infection. CONCLUSIONS: We conclude that
      minimizing length of stay, if possible below 10 days could be a key element to
      achieve a reduction in the neonatal unit's infection rate. However, new studies
      must be performed to ascertain if a strict enforcement of the rules pertaining to
      hand-washing and umbilical catheters manipulation would achieve further
      reductions in the infection rate associated with the umbilical cord
      catheterization.

PMID- 8756214
TI  - [Bacterial pneumonia as a risk marker for new bacterial diseases in patients with
      HIV infection].
AB  - BACKGROUND: Bacterial pneumonias are a main cause of morbidity and mortality
      among patients infected by the HIV. Furthermore, recent data suggest that, under
      certain circumstances, they can be prognostic markers. METHODS: The evolution of
      a cohort of HIV-infected patients, prospectively defined by having suffered a
      pneumonia, was studied with regards to the occurrence of a new pneumonia or death
      from a bacterial disease; the evolution of a control cohort of patients matched
      according to sex, CD4-cell count, previous HIV-disease and zidovudine-treatment
      was compared to the former cohort by means of survival-analysis techniques.
      RESULTS: Forty-nine patients in each group were followed up for a total of 1389
      and 1893 patient-months respectively. In the first group, 17 new first pneumonia
      episodes were diagnosed, as compared to 7 in the second group (relative-risk:
      3.23, 95% confidence interval: 1.34 to 7.79, p = 0.005). Eight of the 31 deaths
      that occurred in the first group were attributed to a bacterial disease, as
      compared to none of the 24 deaths in the second group (p = 0.007, Fisher's exact
      test) (in five of those cases, a bacteria was isolated which was thought to be
      directly related to the death). CONCLUSIONS: HIV-infected patients who suffer a
      bacterial pneumonia have an increased risk of suffering new severe bacterial
      diseases (pneumonia or fatal diseases) as compared to HIV-infected patients with
      similar prognostic features but no previous episodes of pneumonia.

PMID- 8756216
TI  - [Antibiotic sensitivity of anaerobic bacteria isolated during one year (1993)].
AB  - BACKGROUND: The aim of this study was to determine the antimicrobian
      susceptibility of the anaerobe bacteria isolated from clinical samples in the
      authors' department in 1993. METHODS: The minimum inhibitory concentrations of 10
      antimicrobians were determined in microgram/ml for 129 anaerobe bacterias by the
      microdilution in broth method recommended by the NCCLS. RESULTS: All The strains
      were sensitive to chloramphenicol. Metronidazole inhibited all the isolates
      except A. meyeri and 50% of other non spored gram-positive bacilli. Imipenen and
      piperacillin-tazobactam were the most active beta lactamics, with only 1 B.
      fragilis being resistant to both. Clavulanic amoxycillin presented good activity
      with only 5% from the B. fragilis group, 1 F. mortiferum and 2 P. anaerobius
      being resistant. In the B. fragilis group 10% were resistant to cefoxitin and 15%
      to piperacillin. The remaining isolates were sensitive to both antimicrobians.
      Resistance to clindamycin in the B. fragilis group was 16.7%. There were also
      strains resistant to Peptostreptococcus, Prevotella and aerotolerant non spored
      gram-positive bacilli. Penicillin and amoxycillin were the least active
      antimicrobians. CONCLUSIONS: Chloramphenicol, metronidazole, imipenem,
      piperacillin-tazobactam and clavulanic amoxycillin were very effective and showed
      a wide spectrum of activity versus the strains studied. Cefoxitin, piperacillin
      and clindamycin maintain good antianaerobe activity.

PMID- 8756215
TI  - [Transient bacteremia caused by Corynebacterium urealyticum: apropos of 2 cases].
AB  - BACKGROUND: Corynebacterium urealyticum is a pathogen mainly isolated from the
      urinary tract and seldom from the blood. We present two cases of bacteremia
      caused by multiresistant C. urealyticum isolated in two and three blood cultures
      respectively. PATIENTS AND METHODS: The two cases were studied. C. urealyticum
      was isolated from blood cultures and clinical charts were reviewed
      retrospectively. No history of prior antibiotic therapy was observed in either
      patient. Blood cultures were processed using BACTEC NC 730 system (Becton
      Dickinson). The API Coryne system (BioMerieux) was used to identify both strains.
      RESULTS: Despite both patients having not received any antibiotic treatment, they
      improved clinically and microbiologically. Therefore, the episodes were
      considered as transitory bacteremias. CONCLUSION: Although C. urealyticum is not
      common, we believe that it is necessary to identify any diphtheromorphic
      microorganism in blood, when they are clinically significant.

PMID- 8756217
TI  - [Infectious endocarditis 100 years after Osler].

PMID- 8756218
TI  - [Antifungal resistance in opportunistic pathogenic fungi (I). Polyenes and
      fluorocytosine].

PMID- 8756219
TI  - [Cutaneous lesion in an infant].

PMID- 8756220
TI  - [Meningitis caused by Flavobacterium meningosepticum in an adult].

PMID- 8756221
TI  - [Hantavirus infection and the pulmonary syndrome: another new entity to look for
      in our environment?].

PMID- 8756222
TI  - [Meningoencephalitis and pancreatitis caused by the varicella virus, herpes
      zoster].

PMID- 8756223
TI  - [Evaluation of a dot-blot ELISA method, direct immunofluorescence, and shell-vial
      culture for the detection of influenza virus A in nasopharyngeal aspirates].

PMID- 8756224
TI  - ["Gloves and socks" purpura syndrome caused by human parvovirus B19].

PMID- 8756225
TI  - [Sensitivity of Mycobacterium tuberculosis in our environment].

PMID- 8756226
TI  - [Sensitivity of XG medium for the isolation of Salmonella, Shigella, and
      Yersinia].

PMID- 8756227
TI  - [Sinusitis caused by Mycobacterium avium-M. intracellulare in a patient with HIV
      infection].

PMID- 8756228
TI  - [Septic pulmonary embolism and maxillary osteomyelitis].

PMID- 8756229
TI  - [Bacteremia caused by Erysipelothrix rhusiopathiae in an HIV-positive patient].

PMID- 8756230
TI  - [A new specialty?].

PMID- 8756231
TI  - [Resuscitation 96].

PMID- 8756232
TI  - [Warm air convection system and heat loss during vascular surgery].
AB  - OBJECTIVES: To assess the efficacy of a warm air convection (WAC) system to
      supplement the usual physical means (electric blanket, warm i.v. fluids and
      covering of exposed surfaces) for preventing an correcting hypothermia during
      surgery in 2 patient groups scheduled for vascular surgery. PATIENTS AND METHODS:
      We studied 70 consecutive patients scheduled for vascular surgery. Group I: a WAC
      system, in addition to the usual methods, was used to attempt to maintain normal
      body temperatures in 35 consecutive patients. Fifteen were undergoing aortic
      surgery (group Ia) and 20 were undergoing revascularization of the lower
      extremities (group Ib). Group II: only the usual physical methods were used to
      maintain normal temperature in the remaining 35 patients, 15 of whom required
      aortic surgery (group IIa) and 20 of whom were undergoing revascularization of
      the lower extremities (group IIb). Type of anesthesia and monitoring were the
      same in all cases. Esophageal temperature (ET) and room temperatures were
      recorded at baseline and every 30 min until the end of surgery. ET was not
      allowed to fall below 35 degrees C in any patient and WAC was provided to
      patients in group II if they required it. RESULTS: All patients in group II
      experienced a gradual decrease in ET, which became significant 30 min after start
      of surgery in group IIa and 60 min after start of surgery in group IIb.
      Temperature was stable during surgery in all patients in group I. All patients
      with ET of 35 degrees C in group II experienced a rise in temperature, which was
      significant after 60 min. when WAC was used. CONCLUSIONS: In vascular surgery,
      whether aortic or peripheral, patient temperature fell in spite of use of the
      usual physical methods for warming. Adding WAC for upper body warming prevented
      loss of heat. The WAC system was also effective for patients who needed to be
      rewarmed.

PMID- 8756233
TI  - [Body temperature variations during laparoscopic cholecystectomies].
AB  - OBJECTIVE: To study changes over time in body temperature related to insufflation
      of CO2. PATIENTS AND METHOD: Fifty patients were randomly assigned to 2 groups of
      25 to undergo cholecystectomy by either laparoscopy or laparotomy. Total
      intravenous anesthesia with propofol, pancuronium and fentanyl was used in both
      groups. Ventilation was maintained at 0.5 FiO2. Central temperature was
      continuously measured by a distal esophageal thermometer and results were
      recorded every 10 minutes in both groups. All operations lasted approximately 80
      min. RESULTS: We found that temperature gradually decreased over time in both
      groups. In the laparotomy group the decrease reached 0.20 degree C (SD 0.03) at
      80 min. During laparoscopy the temperature decrease was 0.43 degree C (SD 0.04)
      for the same time period. The differences were statistically significant. We
      observed no pathophysiologic repercussions associated with these results.
      CONCLUSIONS: Laparoscopic surgery, even when the abdominal cavity is not exposed
      to room air, induces a loss of temperature that is greater than that of
      laparotomy, because of insufflation of CO2 at 4 degrees C. The decrease was 0.4
      degree C for every 50 l of CO2 insufflated during the study.

PMID- 8756234
TI  - [Can we change the patient's image of the anesthesiologist?].
AB  - OBJECTIVE: To determine whether provision of an information sheet during the
      preanesthesia visit to the patient, and general recommendations for anesthesia,
      can change patients' image of the anesthesiologist. PATIENTS AND METHODS: Two
      groups of 100 patients each were studied before outpatient surgery. Group 1
      (given no information) answered a questionnaire before an interview with the
      anesthesiologist. Group 2 (who were given information) answered the same
      questionnaire, which was accompanied by an information sheet explaining the
      nature of anesthesia, possible risks, operating room and postoperative
      procedures. RESULTS: In group 1,67% identified the anesthesiologist as a
      physician. In group 2, 99% (p < 0.05) were able to do so. In group 1, 48%
      believed that the anesthesiologist works under the surgeon's orders, while only
      27% (p < 0.05) thought so in group 2. The chief of the postanesthesia intensive
      care unit was thought to be a member of the nursing staff by 48% in group 1,
      whereas 95% (p < 0.05) in group 2 identified the chief as an anesthesiologist.
      CONCLUSIONS: The image of anesthesiology and the anesthesiologist can be improved
      by systematically providing an information sheet to patients who are scheduled
      for presurgical study.

PMID- 8756236
TI  - [Anesthetic management in unilateral lung transplantation].
AB  - OBJECTIVE: To describe and evaluate anesthetic treatment during single lung
      transplantation (SLT). PATIENTS AND METHODS: This is a retrospective study of
      patients undergoing SLT during one year of our program's operation. We describe
      the surgical technique and method of anesthesia, which consisted in combined
      general and epidural anesthesia. Systemic and pulmonary arterial pressures, heart
      rate, arterial and mixed venous oxygen saturation were monitored throughout the
      procedure, along with inspired and expired gases and airway pressure. The
      following parameters were recorded for the various phases of surgery: cardiac
      index (CI), right ventricular ejection fraction (REF) and systemic and pulmonary
      vascular resistances, arterial and mixed venous blood gas readings. RESULTS:
      Eight SLT were performed during the study period and the survival rate was 100%.
      PaCO2 and pulmonary artery pressure increased at the start of ventilation of a
      single lung. These values increased again when the pulmonary artery was clamped.
      During this period, however, CI and REF held steady and venous oxygen saturation
      decreased only slightly. Cardiopulmonary bypass was therefore never used. The
      variables returned to normal upon revascularization of the new lung. CONCLUSIONS:
      In spite of the small series studied, the excellent results obtained lead us to
      conclude that our method is appropriate and that SLT is a valid therapeutic
      alternative for our patients.

PMID- 8756235
TI  - [Botulinum toxin: clinical uses and anesthetic implications].
AB  - Botulinum toxin, a neurotoxin responsible for botulism, is at present used to
      treat anomalous muscle contractions. Administration to children and relatively
      uncooperative patients requires general anesthesia, which should be selected
      taking into consideration the special characteristics of the surgical procedure
      and the possible interactions of anesthetic drugs and the toxin.

PMID- 8756237
TI  - [Peridural anesthesia for subcostal cholecystectomy in patients with dilated
      cardiomyopathy. Apropos of 2 cases].
AB  - Two patients with dilated cardiomyopathy (DCM) were considered to be at high risk
      for anesthesia and surgery due to possible complications during and after
      surgery. The anesthetic technique used in such cases must be selected based on
      the type of surgery and the severity of heart disease. We describe the cases of 2
      patients with histories of DCM, arising in a context of alcohol use in one case
      and of ischemia in the other. The patients were scheduled for uncomplicated
      cholecystectomy by subcostal approach under epidural anesthesia. The patients
      remained hemodynamically stable during surgery and there were no complications.
      They were released 26 and 13 days after surgery, respectively. We conclude that
      epidural anesthesia is a valid alternative to general anesthesia in DCM patients
      undergoing subcostal cholecystectomy.

PMID- 8756238
TI  - [Cardio-circulatory response to laryngoscopy. Comparative study between Macintosh
      and McCoy laryngoscopes].
AB  - To assess the cardiocirculatory repercussions of laryngoscopy performed with the
      Macintosh or McCoy laryngoscopes, we studied 20 patients randomly divided into 2
      groups of 10 to undergo laryngoscopy with one or the other of the aforementioned
      instruments. All patients were in good health overall (ASA I or II) and presented
      no criteria for difficult intubation (Mallampati I or II, distance between the
      thyroid and the menton greater than 7 cm and maximum distance between the
      incisors greater than 3.5 cm). The McCoy laryngoscope was associated with
      significantly lower systolic arterial pressure and heart rate.

PMID- 8756239
TI  - [Evaluation of the blood patch using magnetic resonance].

PMID- 8756241
TI  - [General anesthesia in a patient homozygous for the atypical variant of plasma
      pseudocholinesterase].

PMID- 8756240
TI  - [Transesophageal echocardiography during total arthroplasty of the hip].

PMID- 8756242
TI  - [Intracranial complications after endonasal surgery].

PMID- 8756243
TI  - [Anesthesia for laparoscopic cholecystectomy with CO2: comparison of hemodynamic
      and ventilatory behavior using 2 different anesthetic techniques].

PMID- 8756244
TI  - [Massive hemorrhage caused by musculoskeletal trauma in the dorsal region].

PMID- 8756245
TI  - [Transient bilateral hearing loss after spinal anesthesia].

PMID- 8756246
TI  - [Detection of dystrophin gene mutation carrier state].
AB  - RFLP polymorphism and the sequence of repeated CA were analysed by means of
      polymerase chain reaction in 62 families in which cases of DMD/BMD had occurred.
      The established carriers were suggested to undergo prenatal examinations for
      avoiding giving birth to a child with Duchenne or Becker type of muscular
      dystrophy.

PMID- 8756247
TI  - [Effects of prednisone and azathioprine treatment on oligoclonal IGG in the
      cerebrospinal fluid of multiple sclerosis patients. Preliminary communication].
AB  - The influence of high-dose prednisone and azathioprine therapy on oligoclonal IgG
      in the CSF of MS patients was studied. The oligoclonal bands were present in 93%
      of patients treated with prednisone and in 90% of patients treated with
      azathioprine. After the treatment with prednisone, the oligoclonal bands density
      was diminished in 3 patients, and after the treatment with azathioprine in 1
      patient. The number of bands and their pattern remained the same.

PMID- 8756248
TI  - [Lipid metabolism parameters in patients with multi-infarct dementia and
      Alzheimer's type dementia].
AB  - The concentrations were determined of triglycerides (TG), total cholesterol (Ch),
      high density fraction of (HDL-Ch), low density fraction of cholesterol (LDL-Ch),
      apolipoprotein B (apo-B) in patients with dementia of Alzheimer type (DAT, 14
      patients) and multi-infarct dementia (MID, 63 patients). No significant
      differences in the estimated lipid parameters in both groups were found, except
      the calculated value of atherogenic index (Ch/HDL-Ch), which was significantly
      higher in patients with MID. Our results suggest that this parameter is a much
      more sensitive atherogenic indicator in blood-vessels than other tested lipid
      parameters. This finding may influence the therapeutic approach to patients with
      dementia.

PMID- 8756250
TI  - [The attempt to define reciprocal relations between radicular and pseudoradicular
      syndrome in patients with lumbar disc herniation (1dh)].
AB  - Based on history and clinical examination in 100 patients with Idh we selected
      four clinical features characteristic of radicular and pseudoradicular
      (spondylogenic) syndrome. The choice was based on data from review of literature.
      We confirmed that pseudoradicular syndrome features appeared in most of Idh
      patients. Of the 100 patients in 20% pseudoradicular syndrome features prevailed,
      14% experienced mainly radicular syndrome features and 66% patients presented
      mixed clinical picture. We suggest that above relationships should be considered
      in clinical practice.

PMID- 8756249
TI  - [Detection of oligoclonal immunoglobulin G in the cerebrospinal fluid of patients
      with multifocal vascular lesions of the CNS].
AB  - Vascular diseases of CNS are usually a result of certain risk factors. In a
      number of cases vascular diseases are caused by inflammatory process within
      arteries. Establishing the intrathecal synthesis of immunoglobulins is an
      important indicator of the inflammatory process in the CNS. 16 patients with
      multifocal vascular lesions in neuroimaging examinations (MRI or CT), were
      analysed for the frequency of occurrence of inflammatory process within the CNS.
      The presence of intrathecal synthesis of IgG was established by mathematical
      formulas and presence oligoclonal IgG bands. In some patients presence of
      oligoclonal IgG bands was found, and regarded responsible for stroke. In this
      group the patients were younger, and mainly without other risk factors for
      vascular diseases. In the majority they were patients with systemic inflammatory
      process (e.g. SLE). The establishing of inflammatory process within the CNS
      sometimes has therapeutic implications.

PMID- 8756251
TI  - [Antigravity suit used for neurosurgical operations in sitting position].
AB  - The aviator's antigravity suit (G-suit) was used for 40 operations on
      neurosurgical patients operated on in sitting position. The G-suit was filled
      with air to 0.2 atmosphere (20 kPa) pressure in 26 cases, and 0.3 atm. (30 kPa)
      in 14 cases. In all cases G-suit filling was followed by central venous pressure
      rise and mean arterial pressure rise. Venous air embolism was found in 5 (12.5%)
      patients. No other complications connected with the use of G-suit were observed.

PMID- 8756252
TI  - [Surgical treatment of meningiomas of medial part of sphenoid ala and en-plaque
      meningiomas of perisellar area].
AB  - The authors present some clinical aspects of their own experience in the
      operative treatment of clinoidal and en-plaque suprasellar meningiomas which
      account for 5.6% of all intracranial meningiomas in Department of Neurosurgery
      treated in the years 1987-93. Visual loss was the first symptom of disease. In
      conclusion, the authors stress the still unacceptably long period between the
      onset of symptoms and correct diagnosis. Possibilities of total removal are
      limited by the size of tumour and compression of adjacent structures, and the
      chance for visual improvement is low for that reasons. Visual improvement was
      observed in only one case after surgery, however in 5 cases worsening of visual
      acuity was noted in postoperative period. Mortality rate was 6.2%. Adjuvant
      radiotherapy was performed in non patient. Long term results in ophthalmological
      and neurological aspects are discussed.

PMID- 8756253
TI  - [Mitochondrial diseases. Part I -- general review].
AB  - Inborn mitochondrial diseases (MD) may result from molecular defects involving
      the mitochondrial or the nuclear genome, so they may be transmitted maternally or
      as Mendelian traits; some cases occur sporadically. Numerous secondary causes of
      mitochondrial disorders are also known. Impairment of mitochondrial oxidation
      leads to the defective energy production, and further, to cellular damage. MD
      should be suspected when progressive signs occur, especially involving nervous
      system and muscles; other organs as heart, liver and kidney may also be affected.

PMID- 8756255
TI  - [The concept of encephalopathies -- paper for discussion].
AB  - The term "encephalopathy" has not yet been strictly defined. In textbooks about
      20 adjectives can be found in connection with this term. All encephalopathies
      have certain features in common: 1. the cause of brain damage is known, 2. the
      neurological syndrome is diffuse or disseminated, 3. there is the syndrome of
      organic brain damage (most frequently with dementia). Encephalopathies can be
      divided into congenital and acquired. Congenital ones are: encephalopathy
      following perinatal injury or fetal infection. Acquired: post-traumatic, toxic,
      vascular (hypertensive and atherosclerotic), metabolic, postinflammatory. On the
      basis of analysis of clinical findings and causes the conclusion may be reached
      that encephalopathy is a sequela of diffuse organic brain damage, that is, it is
      a "status post...", but this excludes certain encephalopathies recognize as yet
      (hypertensive encephalopathy). In medical expertise more precise diagnosis should
      be required, especially for post-traumatic encephalopathy.

PMID- 8756254
TI  - [Mitochondrial diseases. Part II -- diagnosis and detailed review].
AB  - The diagnosis of mitochondrial disease (MD) requires biochemical investigations
      of body fluids, particularly with respect to lactate and pyruvate elevation.
      Cardiological and ophtalmological examinations may also be helpful, as well as
      cerebral imaging. Tissue sampling, especially muscle biopsy and DNA analysis are
      important. Neuropathological findings consist of nonspecific spongiform lesions
      of gray matter, neuronal loss and sometimes demyelination with different
      topographic patterns. Some, more frequently occurring mitochondrial diseases and
      therapeutic attempts are reviewed.

PMID- 8756256
TI  - [A case of fat embolism of brain confirmed by magnetic resonance imaging].
AB  - This is a case report of 21 years old man with a multifragment fracture of shank
      bones acquired in a car accident. Two days after accident symptoms of cerebral
      fat embolisms developed. Presence of multiple fat emboli was confirmed in MRI.

PMID- 8756257
TI  - [Polyneuropathy in the course of Hodgkin's disease: case report].
AB  - Polyneuropathy in neoplastic process practically may occur in every stage, before
      clinical signs, together with clinical signs and in the last period. In some
      percent of patients polyneuropathy may outstrip manifestation of neoplastic
      process even for many years. We present a 61-year-old patient in whom signs of
      polyneuropathy appeared before the signs of essential disease - Hodgkin's
      disease. Our case confirms the necessity of very careful and precise diagnostics
      of polyneuropathy with unclear aetiology.

PMID- 8756258
TI  - [A case of coexistent meningioma with epidural hematoma in a woman aged 74
      years].

PMID- 8756259
TI  - [Embolization of AVM's of thoracic spinal cord with histoacryl glue].
AB  - The authors present two cases of inoperable AVM's of thoracic spinal cord
      successfully treated by embolization with histoacryl glue (B. Brown Melsungen
      AG). The glue used for embolization is characterized by instant polymerization
      when comes in contact with blood. A mass of polymer is visible on X-ray thanks to
      contrast medium Lipiodol and metallic powder Tungsten that are added to glue and
      injected together with the latter. In the first case, a female who presented with
      paraparesis and walked only with assistance embolization performed in one session
      resulted in neurological improvement enabling independent walking at follow-up 2
      yrs later. In the second case of a young male not walking for severe paraparesis
      embolization performed in three sessions resulted in significant neurological
      recovery. 10 days after the first session the patient became ambulatory. 6 months
      after treatment he presented with mild paraparesis and was still ambulatory and
      leading independent life. In each case embolization was performed after balloon
      occlusion test during which the function of spinal cord was monitored by
      somatosensory evoked potentials and neurological assessment.

PMID- 8756260
TI  - [From the history of Polish neurology].

PMID- 8756261
TI  - Two derivatives of lithium isodicyclopentadienide: [(1,2,3,3a,7a-eta)-4,5,6,7
      tetrahydro-4,7-methanoindenido] (N,N,N1,N1-tetramethylethylenediamine)lithium and
      Bis (1,4,7,10-tetraoxacyclododecane)-lithium(1+) Bis[(1,2,3,3a,7a-eta)-4,5,6,7
      tetrahydro-4,7-methanoindenido]lithate(1- ).
AB  - Selective crystallization of a solution of lithium isodicyclopentadienide,
      (isodiCp)Li, in dry thf or diethyl ether under argon has produced two lithium
      complexes: (isodiCp)Li(TMEDA), [Li(C10H11)(C6H16N2)], (4), and [Li(12-crown
      4)2]+. [Li(isodiCp)2]-, [Li(C8H16O4)2]-[Li(C10H11)2], (5). In (4) the Li+ ion is
      coordinated to the two N atoms of the disordered TMEDA and is eta 5-coordinated
      to the Cp ring of the isodiCp ligand. The Li-(Cp ring centroid) distance is 1.906
      (7) A. In (5) there are two independent half-molecules of the anion and one
      molecule of the cation in the asymmetric unit. In each anion, the Li+ ion
      occupies a crystallographic inversion center and is eta 5-coordinated to the two
      Cp rings of two isodiCp ligands. The Cp rings are in a staggered arrangement, as
      required by the inversion center. The Li-(Cp ring centroid) distances for the two
      anions are 1.987 (3) and 2.008 (3) A. In the cation of (5), the Li+ ion is
      coordinated to two 12-crown-4 ligands, one of which is disordered. Both (4) and
      (5) exhibit exo coordination of the Li+ ion to the isodiCp ligand, with a
      resultant slight endo bending of this ligand.

PMID- 8756262
TI  - O-phospho-DL-threonine and O-phospho-L-threonine compared with their serine
      analogs.
AB  - In crystals of O-phospho-DL-threonine and O-phospho-L-threonine, the molecules
      are zwitterions HO3-POCH-(CH3)CH(NH3+)CO2H linked by three-dimensional networks
      of strong P-O-H...O = P, C-O-H...O = P, N-H...O = P and N-H...O = C hydrogen
      bonds with (O...O) = 2.55 (3) A and (N...O) = 2.84 (4) A. Both the molecular
      conformations and the nearest-neighbor hydrogen-bonded surroundings are very
      similar in the racemic and enantiomeric crystals of the threonine compounds, but
      earlier studies of crystals of the analogous serine compounds have shown that the
      serine zwitterions HO3-POCH2CH(NH3+)CO2H have different conformations about the C
      beta-O gamma-P phosphate ester bonds and different hydrogen-bonded surroundings.

PMID- 8756264
TI  - Structural studies of mitomycins. VII. Mitomycin G.
AB  - The title compound, [1aS-(1a alpha, 8a alpha, 8b alpha)]-6-amino-1, 1a,2,8,8a,8b
      hexahydro-8a-methoxy-1,5-dimethyl-8-methyleneazirino [2',3':3,4]pyrrolo[1,2
      a]indole-4,7-dione, C15H17N3O3, is a derivative of the mitomycins, which are
      antitumor antibiotics. The quinone O atoms deviate significantly from the least
      squares plane of the quinone ring.

PMID- 8756265
TI  - 1,2-diacetyl-4-phenyl-1,2,4-triazolidine-3,5-dione.
AB  - The title crystal, C12H11N3O4, contains three essentially identical molecules in
      the asymmetric unit. The triazole rings in the three independent molecules are
      planar within 0.014 A. The N atom containing the phenyl substituent is trigonal,
      the sum of the three bond angles being 359.5 degrees. The other two N atoms are
      slightly pyramidal, the sum of the three bond angles being 346 degrees. The two
      acetyl groups are twisted out of the plane of the triazole ring by an average of
      33 degrees and are trans to each other.

PMID- 8756266
TI  - Anthracene-1,8-dicarboxylic acid.
AB  - Anthracene-1,8-dicarboxylic acid, C16H10O4, crystallized in the
      noncentrosymmetric space group P2(1)2(1)2(1). The carboxyl H and O atoms are
      ordered. The carboxyl groups make angles of 13.9 (2) and 21.6 (2) degrees with
      the best-fit core plane and the average distance of the core atoms from this
      plane is 0.018 (12) A. The anthracene core displays near twofold symmetry. Each
      molecule is involved in cyclic-dimer hydrogen bonding with two other molecules so
      as to form zigzag chains of hydrogen-bonded molecules which are not cross-linked
      with one another. These discrete chains are separated from each other by C...C,
      C...H and H...H closest approaches.

PMID- 8756267
TI  - A study of the bifurcation behaviour of a model of flow through a collapsible
      tube.
AB  - Most of the elastic tubes found in the mammalian body will collapse from a
      distended circular cross section and when collapsed may undergo flow-induced
      oscillations. A mathematical model describing fluid flow in a collapsible tube is
      analysed using the software package AUTO-86. AUTO-86 is used for continuation and
      bifurcation problems in systems of non-linear ordinary differential equations.
      The model is third-order lumped-parameter type and is based on the classical
      "Starling resistor"; it describes the unsteady flow behaviour and, in particular,
      the experimentally observed self-excited oscillations, in a way which is simple
      enough to give physical understanding, yet still firmly based on fluid mechanical
      principles. Some of the bifurcation types found in this model bear close
      resemblance to the types suggested by experimental observations of self-excited
      oscillations in collapsible tubes; they thus shed some light on the various
      topological changes which occur in practice, particularly in view of the fact
      that some of the points found numerically are difficult to achieve
      experimentally, while the existence of others can only be inferred indirectly and
      uncertainly from experiment.

PMID- 8756269
TI  - On the pressure and flow-rate distributions in tree-like and arterial-venous
      networks.
AB  - A solution algorithm yielding the pressure and flow-rate distributions for steady
      flow in an arbitrary, tree-like network is provided. Given the tree topology, the
      conductance of each segment and the pressure distribution at the boundary nodes,
      the solution is obtained from a simple recursion based on perfect Gauss
      elimination. An iterative solution method using this algorithm is suggested to
      solve for the pressure and flow-rate distributions in an arbitrary diverging
      converging (arterial-venous) network consisting of two tree-like networks which
      are connected to each other at the capillary nodes. A number of special solutions
      for tree-like networks are obtained for which the general algorithm is either
      simplified or can be replaced by closed form solutions of the pressure and flow
      rate distributions. These special solutions can also be obtained for each tree of
      diverging-converging networks having particular topologies and conductance
      distributions. Sample numerical results are provided.

PMID- 8756271
TI  - Gender differences in perceptions of household labor.
AB  - The perceptions of household labor contributions of 277 individuals were
      examined. At the time of the study, participants were married or cohabiting,
      although no couples participated. The relationship between perceptions of
      contributions to household labor and the independent variables of gender
      ideology, a wife's relative contribution to family income, a husband's time
      availability, and family demographic variables were studied. Responses of people
      in dual-earner arrangements were compared with responses of people in households
      in which the woman was a full-time homemaker. In dual-earner families, the
      woman's relative contribution to family income and number of children were
      negatively associated with perceptions of her contributions to household tasks
      relative to those of her partner. In both dual-earner arrangements and situations
      in which the wife was a full-time homemaker, a statistically significant
      association was found between the perceived division of household labor and
      gender. Women were more likely than men to report that a women contributes
      significantly more to housework than the man. Men in dual-earner relationships
      reported the smallest contribution to household labor by women.

PMID- 8756270
TI  - A mathematical model for fibro-proliferative wound healing disorders.
AB  - The normal process of dermal wound healing fails in some cases, due to fibro
      proliferative disorders such as keloid and hypertrophic scars. These types of
      abnormal healing may be regarded as pathologically excessive responses to
      wounding in terms of fibroblastic cell profiles and their inflammatory growth
      factor mediators. Biologically, these conditions are poorly understood and
      current medical treatments are thus unreliable. In this paper, the authors apply
      an existing deterministic mathematical model for fibroplasia and wound
      contraction in adult mammalian dermis (Olsen et al., J. theor. Biol. 177, 113
      128, 1995) to investigate key clinical problems concerning these healing
      disorders. A caricature model is proposed which retains the fundamental cellular
      and chemical components of the full model, in order to analyse the spatiotemporal
      dynamics of the initiation, progression, cessation and regression of fibro
      contractive diseases in relation to normal healing. This model accounts for
      fibroblastic cell migration, proliferation and death and growth-factor diffusion,
      production by cells and tissue removal/decay. Explicit results are obtained in
      terms of the model processes and parameters. The rate of cellular production of
      the chemical is shown to be critical to the development of a stable pathological
      state. Further, cessation and/or regression of the disease depend on appropriate
      spatiotemporally varying forms for this production rate, which can be understood
      in terms of the bistability of the normal dermal and pathological steady states-a
      central property of the model, which is evident from stability and bifurcation
      analyses. The work predicts novel, biologically realistic and testable pathogenic
      and control mechanisms, the understanding of which will lead toward more
      effective strategies for clinical therapy of fibro-proliferative disorders.

PMID- 8756272
TI  - When careers reach a dead end: identification of occupational crisis states.
AB  - The reliability and validity of the Occupational Crisis Scale, (OCS; Hutri,
      1995a) were examined in 3 separate studies. The OCS was developed to identify
      employees who are at a dead end in their job or career. Participants were
      employees from various occupations, psychology students, and previous vocational
      counseling clients. The results demonstrated the OCS's internal consistency, test
      retest reliability, construct validity, divergent and convergent validity, as
      well as changes in occupational crisis states after a 1-year follow-up. The
      prevalence of occupational crises was rated to be at least 1 for every 30
      employees. All identified crisis participants were women. Occupational crises
      were related to long consideration of career change, suggesting that the crises
      were of developmental origin. The findings are compared with the results from a
      preliminary study among vocational counseling clients. The use of the OCS to
      assist troubled employees is discussed.

PMID- 8756273
TI  - Mental constructs and the cognitive reconstruction of the Berlin wall.
AB  - In this study of how to change people's conceptions of certain facts (i.e., the
      position of the Berlin Wall), a surprising psychological phenomenon was
      discovered. In the trial test, instead of designing a wall to enclose West
      Berlin, most people described and drew a short and straight wall that divided the
      city from north to south. Two methods were created, based on two general
      information-processing components involved in problem solving, to study how
      people might repair their misconceptions by themselves. The do-it-yourself method
      consisted of providing people with the task of thinking about how to build the
      wall and then drawing it, instead of just asking them to draw it. The distance-to
      goal evaluation method consisted of asking the participants how the wall they had
      drawn would actually prevent passage from East Germany to West Berlin. The
      results showed that both methods had important effects in repairing
      misconceptions, but improvement in performance with the distance-to-goal method
      was less significant for those participants who were first provided the task of
      thinking about how to build the wall. These findings are consistent with the
      hypothesis that awareness of functional properties plays an important role in
      structuring and restructuring mental constructs.

PMID- 8756274
TI  - A note on whether spousal caregivers try to control their environment or
      themselves.
AB  - In this study, a two-process model of control (Rothbaum, Weisz, & Snyder, 1982)
      was used to investigate spousal caregivers' control in stressful situations.
      According to Rothbaum et al., primary control occurs when individuals retain
      control by changing their environment (other people, objects, or events), whereas
      secondary control occurs when individuals retain control by changing their own
      cognitions or emotions to adapt to the environment. In an exploration of whether
      caregivers would use primary or secondary control in caring for a spouse with
      dementia, 32 caregivers described a stressful situation they found difficult to
      control. Most of the participants used primary control to handle situations that
      focused on behavioral problems. Additional analyses indicated that most of the
      caregivers, in fact, used a combination of primary and secondary control.

PMID- 8756275
TI  - Emotional and psychological consequences of sexual harassment: a descriptive
      study.
AB  - The emotional and psychological consequences of sexual harassment were
      investigated. On the basis of previous empirical evidence concerning the
      correlates of sexual harassment, the role of the working relationship between
      harasser and target, type of harassment, gender composition of the work group,
      duration of the harassment, and gender were examined in relation to two
      psychological states: feelings about work and emotional/physical condition.

PMID- 8756276
TI  - Cerebral laterality in affect and affective illness: a review.
AB  - It is generally claimed that affect processing is a right hemisphere function. It
      is also claimed that right hemisphere dysfunction is characteristic of depressive
      illness. These claims are not accepted without controversy, and it has been found
      that the relationship between affect processing and affective illness in terms of
      intra- and interhemispheric role is not straightforward. Two types of studies
      were reviewed in this context: behavioral and electrophysiological. Potential
      confounding effects are discussed.

PMID- 8756277
TI  - The limb field mesoderm determines initial limb bud anteroposterior asymmetry and
      budding independent of sonic hedgehog or apical ectodermal gene expressions.
AB  - We have analyzed the pattern of expression of several genes implicated in limb
      initiation and outgrowth using limbless chicken embryos. We demonstrate that the
      expressions of the apical ridge associated genes, Fgf-8, Fgf-4, Bmp-2 and Bmp-4,
      are undetectable in limbless limb bud ectoderm; however, FGF2 protein is present
      in the limb bud ectoderm. Shh expression is undetectable in limbless limb bud
      mesoderm. Nevertheless, limbless limb bud mesoderm shows polarization manifested
      by the asymmetric expression of Hoxd-11, -12 and -13, Wnt-5a and Bmp-4 genes. The
      posterior limbless limb bud mesoderm, although not actually expressing Shh, is
      competent to express it if supplied with exogenous FGF or transplanted to a
      normal apical ridge environment, providing further evidence of mesodermal
      asymmetry. Exogenous FGF applied to limbless limb buds permits further growth and
      determination of recognizable skeletal elements, without the development of an
      apical ridge. However, the cells competent to express Shh do so at reduced
      levels; nevertheless, Bmp-2 is then rapidly expressed in the posterior limbless
      mesoderm. limbless limb buds appear as bi-dorsal structures, as the entire limb
      bud ectoderm expresses Wnt-7a, a marker for dorsal limb bud ectoderm; the
      ectoderm fails to express En-1, a marker of ventral ectoderm. As expected, C
      Lmx1, which is downstream of Wnt-7a, is expressed in the entire limbless limb bud
      mesoderm. We conclude that anteroposterior polarity is established in the initial
      limb bud prior to Shh expression, apical ridge gene expression or dorsal-ventral
      asymmetry. We propose that the initial pattern of gene expressions in the
      emergent limb bud is established by axial influences on the limb field. These
      permit the bud to emerge with asymmetric gene expression before Shh and the
      apical ridge appear. We report that expression of Fgf-8 by the limb ectoderm is
      not required for the initiation of the limb bud. The gene expressions in the pre
      ridge limb bud mesoderm, as in the limb bud itself, are unstable without
      stimulation from the apical ridge and the polarizing region (Shh) after budding
      is initiated. We propose that the defect in limbless limb buds is the lack of a
      dorsal-ventral interface in the limb bud ectoderm where the apical ridge
      induction signal would be received and an apical ridge formed. These observations
      provide evidence for the hypothesis that the dorsal-ventral ectoderm interface is
      a precondition for apical ridge formation.

PMID- 8756278
TI  - Identified central neurons convey a mitogenic signal from a peripheral target to
      the CNS.
AB  - Regulation of central neurogenesis by a peripheral target has been previously
      demonstrated in the ventral nerve cord of the leech Hirudo medicinalis (Baptista,
      C. A., Gershon, T. R. and Macagno, E. R. (1990). Nature 346, 855-858)
      Specifically, innervation of the male genitalia by the fifth and sixth segmental
      ganglia (the sex ganglia) was shown to trigger the birth of several hundred
      central neurons (PIC neurons) in these ganglia. As reported here, removal of the
      target early during induction shows that PIC neurons can be independently induced
      in each side of a ganglion, indicating that the inductive signal is both highly
      localized and conveyed to each hemiganglion independently. Further, since recent
      observations (Becker, T., Berliner, A. J., Nitabach, M. N., Gan, W.-B. and
      Macagno, E. R. (1995). Development, 121, 359-369) had indicated that efferent
      projections are probably involved in this phenomenon, we individually ablated all
      possible candidates, which led to the identification of two central neurons that
      appear to play significant roles in conveying the inductive signal to the CNS.
      Ablation of a single ML neuron reduced cell proliferation in its own hemiganglion
      by nearly 50%, on the average. In contrast, proliferation on the opposite side of
      the ganglion increased by about 25%, suggesting the possibility of a compensatory
      response by the remaining contralateral ML neuron. Simultaneous ablation of both
      ML neurons in a sex ganglion caused similar reductions in cell proliferation in
      each hemiganglion. Deletion of a single AL neuron produced a weaker (7%) but
      nonetheless reproducible reduction. Ablation of the other nine central neurons
      that might have been involved in PIC neuron induction had no detectable effect.
      Both ML and AL neurons exhibit ipsilateral peripheral projections, and both
      arborize mostly in the hemiganglion where they reside. Thus, we conclude that
      peripheral regulation of central neurogenesis is mediated in the leech by
      inductive signals conveyed retrogradely to each hemiganglion by specific central
      neurons that innervate this target and the hemiganglion they affect.

PMID- 8756279
TI  - Long-term in vitro culture and characterisation of avian embryonic stem cells
      with multiple morphogenetic potentialities.
AB  - Petitte, J.N., Clarck, M.E., Verrinder Gibbins, A. M. and R. J. Etches (1990;
      Development 108, 185-189) demonstrated that chicken early blastoderm contains
      cells able to contribute to both somatic and germinal tissue when injected into a
      recipient embryo. However, these cells were neither identified nor maintained in
      vitro. Here, we show that chicken early blastoderm contains cells characterised
      as putative avian embryonic stem (ES) cells that can be maintained in vitro for
      long-term culture. These cells exhibit features similar to those of murine ES
      cells such as typical morphology, strong reactivity toward specific antibodies,
      cytokine-dependent extended proliferation and high telomerase activity. These
      cells also present high capacities to differentiate in vitro into various cell
      types including cells from ectodermic, mesodermic and endodermic lineages.
      Production of chimeras after injection of the cultivated cells reinforced the
      view that our culture system maintains in vitro some avian putative ES cells.

PMID- 8756280
TI  - Role of TGF beta s and BMPs as signals controlling the position of the digits and
      the areas of interdigital cell death in the developing chick limb autopod.
AB  - The establishment of the digital rays and the interdigital spaces in the
      developing limb autopod is accompanied by the occurrence of corresponding domains
      of expression of TGF beta s and BMPs. This study analyzes whether these
      coincident events are functionally correlated. The experiments consisted of local
      administration of TGF beta-1, TGF beta-2 or BMP-4 by means of heparin or Affi-gel
      blue beads to the chick limb autopod in the stages preceding the onset of
      interdigital cell death. When beads bearing either TGF beta-1 or -2 were
      implanted in the interdigits, the mesodermal cells were diverted from the death
      program forming ectopic cartilages or extra digits in a dose- and stage-dependent
      fashion. This change in the interdigital phenotype was preceded by a precocious
      ectopic expression of ck-erg gene around the bead accompanied by down-regulation
      of bmp-4, msx-1 and msx-2 gene expression. When BMP-beads were implanted in the
      interdigital spaces, programmed cell death and the freeing of the digits were
      both accelerated. Implantation of beads bearing BMP-4 at the tip of the growing
      digits was followed by digit bifurcation, accompanied by the formation of an
      ectopic area of cell death resembling an extra interdigit, both morphologically
      and molecularly. The death-inducing effect of the BMP beads and the chondrogenic
      inducing effect of the TGF beta beads were antagonized by the implantation of an
      additional bead preabsorbed with FGF-2, which constitutes a signal characteristic
      of the progress zone. It is concluded that the spatial distribution of digital
      rays and interdigital spaces might be controlled by a patterned distribution of
      TGF beta s and BMPs in the mesoderm subjacent to the progress zone.

PMID- 8756281
TI  - Xenopus mothers against decapentaplegic is an embryonic ventralizing agent that
      acts downstream of the BMP-2/4 receptor.
AB  - Dorsal-ventral patterning in vertebrate embryos is regulated by members of the
      TGF-beta family of growth and differentiation factors. In Xenopus the activins
      and Vg1 are potent dorsal mesoderm inducers while members of the bone
      morphogenetic protein (BMP) subclass pattern ventral mesoderm and regulate
      ectodermal cell fates. Receptors for ligands in the TGF-beta superfamily are
      serine-threonine kinases, but little is known about the components of the signal
      transduction pathway leading away from these receptors. In Drosophila the
      decapentaplegic protein (dpp), a homolog of vertebrate BMP-2 and BMP-4, functions
      in dorsal-ventral axial patterning, and a genetic screen for components involved
      in signaling by dpp has identified a gene named mothers against decapentaplegic
      (Mad). Mad encodes a unique, predicted cytoplasmic, protein containing no readily
      identified functional motifs. This report demonstrates that a gene closely
      related to Drosophila Mad exists in Xenopus (called XMad) and it exhibits
      activities consistent with a role in BMP signaling. XMad protein induces ventral
      mesoderm when overexpressed in isolated animal caps and it ventralizes embryos.
      Furthermore, XMad rescues phenotypes generated by a signaling-defective, dominant
      negative, BMP-2/4 receptor. These results furnish evidence that XMad protein
      participates in vertebrate embryonic dorsal-ventral patterning by functioning in
      BMP-2/4 receptor signal transduction.

PMID- 8756282
TI  - Late emigrating neural crest cells migrate specifically to the exit points of
      cranial branchiomotor nerves.
AB  - Morphological segmentation of the avian hindbrain into rhombomeres is also
      reflected by the emergent organisation of branchiomotor nerves. In each case, the
      motor neurons of these nerves lie in two adjacent rhombomeres (e.g. of the Vth
      nerve in r2 and r3, VIIth in r4 and r5 etc.), and their outgrowing axons emerge
      into the periphery through defined exit points in rhombomeres r2, r4 and r6,
      respectively. Sensory axons of the cranial ganglia also enter the neuroepithelium
      at the same points. Motor axon outgrowth through experimentally rotated
      rhombomeres has suggested that a chemoattractive mechanism, involving the exit
      points, may form a component of their guidance. Yet so far, nothing is known
      about the establishment of the exit points or the identity of the cells that form
      them. In this study, we describe a group of late emigrating cranial neural crest
      cells which populate specifically the prospective exit points. Using chimaeras in
      which premigratory chick neural crest had been replaced orthotopically by quail
      cells, a population of neural crest was found to leave the cranial neural tube
      from about stage 10+ onwards and to migrate directly to the prospective exit
      points. These cells define the exit points by stage 12+, long before either motor
      or sensory axons have grown through them. The entire neural crest population of
      exit point cells expresses the recently described cell adhesion molecule c-cad7.
      Further, heterotopic grafting experiments show that midbrain and spinal cord
      crest, grafted at late stages in place of r4 crest, share the same migratory
      behaviour to the facial nerve exit points and express the same markers as cells
      contributed by the native r4 crest. It was not possible to generate new exit
      points in odd numbered rhombomeres simply by experimentally increasing their
      (normally insignificant) amount of crest production. Initiation of the exit point
      region probably lies, therefore, in the neuroepithelium.

PMID- 8756283
TI  - Central projections of persistent larval sensory neurons prefigure adult sensory
      pathways in the CNS of Drosophila.
AB  - We have used a GAL4 enhancer-trap line driving the expression of a lacZ construct
      to examine the reorganisation of an identified group of proprioceptive sensory
      neurons during metamorphosis in Drosophila. The results show that whilst most
      larval sensory neurons degenerate during the first 24 hours of metamorphosis a
      segmentally repeated array of 6 neurons per segment persists into the adult
      stages to become functional adult neurons. These sensory neurons retain their
      axonal projections in the central nervous system intact and unchanged throughout.
      The adult sensory neuron axons enter the central nervous system at around 44
      hours after puparium formation. Most of these axons grow along the pathways
      defined by the persistent larval sensory axons. The ordering of the adult sensory
      projections is, therefore, established upon the larval pattern of projections.
      The possibility that the larval neurons act as guidance cues for organising the
      ordered arrays of sensory neurons is discussed.

PMID- 8756284
TI  - Xom: a Xenopus homeobox gene that mediates the early effects of BMP-4.
AB  - Bone morphogenetic protein-4 (BMP-4) is thought to play an important role in
      early Xenopus development by acting as a "ventralizing factor' and as an
      epidermal determinant: local inhibition of BMP-4 function in whole embryos causes
      the formation of an additional dorsal axis, and inhibition of BMP-4 function in
      isolated ectodermal cells causes the formation of neural tissue. In this paper we
      describe a homeobox-containing gene whose expression pattern is similar to that
      of BMP-4, whose expression requires BMP-4 signalling and which, when over
      expressed, causes a phenotype similar to that caused by over-expression of BMP-4.
      We suggest that this gene, which we call Xom, acts downstream of BMP-4 to mediate
      its effects.

PMID- 8756285
TI  - An altered body plan is conferred on Arabidopsis plants carrying dominant alleles
      of two genes.
AB  - In this paper, we describe a late-flowering ecotype of Arabidopsis, Sy-0, in
      which the axillary meristems maintain a prolonged vegetative phase, even though
      the primary shoot apical meristem has already converted to reproductive
      development. This novel heterochronic shift in the development of axillary
      meristems results in the formation of aerial rosettes of leaves at the nodes of
      the primary shoot axis. We present evidence that the aerial-rosette phenotype
      arises due to the interaction between dominant alleles of two genes: ART, aerial
      rosette gene (on chromosome 5) and EAR, enhancer of aerial rosette (on chromosome
      4): EAR has been tentatively identified as a new allele of the FRI locus. The
      possible role of these two genes in the conversion of shoot apical meristems to
      reproductive development is discussed.

PMID- 8756286
TI  - Requirement of neurotrophin-3 for the survival of proliferating trigeminal
      ganglion progenitor cells.
AB  - The aim of this study was to identify the physiological role of neurotrophin-3
      (NT-3) in the development of trigeminal ganglion sensory neurons. For this
      purpose we have analysed mice carrying a deletion in the NT-3 gene (NT-3-/-
      mice). In these mice, by embryonic day (E) 11.25% of the trigeminal ganglion
      neurons were absent and one day later, approximately 50% were absent, after which
      no further significant changes were observed. Mice carrying one functional NT-3
      gene (NT-3+/- mice) displayed a less severe deficit than that of NT-3-/- mice.
      Whereas programmed cell death occurred between E12 and E14 in the control mice,
      pronounced excessive cell death was apparent prior to this in the NT-3-/- mice.
      The excessive cell death led to a progressive decline in the number of
      proliferating cells without a significant change in the fraction of dividing
      cells and total number of neurons, indicating that the neuronal deficit of NT-3-/
      mice was caused by cell death of trigeminal ganglion progenitors. Furthermore,
      the degenerating cells had incorporated BrdU, a nucleotide analogue which labels
      proliferating cells, and expressed nestin, a marker for progenitor cells. Only
      rarely were degenerating cells seen to express peripherin, present in postmitotic
      neurons. These data provide evidence that NT-3 is a survival factor for
      trigeminal ganglion progenitor cells, and suggests that limiting amounts of NT-3
      could influence progenitor cell numbers during gangliogenesis.

PMID- 8756287
TI  - The SM 22 promoter directs tissue-specific expression in arterial but not in
      venous or visceral smooth muscle cells in transgenic mice.
AB  - The transcriptional signals underlying smooth muscle differentiation are
      currently unknown. We report here the complete sequence and characterization of
      the single mouse gene for the smooth muscle-specific protein SM 22 and the
      transcriptional activity of its promoter in cultured smooth muscle cells in vitro
      and in transgenic mice. In the transgenic animals, promoter constructs ranging in
      length from 445 to 2126 bp directed reporter expression initially in the heart
      and the somites of embryos and subsequently in the arteries of the vascular
      system, but in none of the visceral muscles, nor in the veins. Expression in the
      heart was spatially restricted to the presumptive right ventricle and outflow
      tract and disappeared in the adult. Likewise, expression in the somites was only
      transitory and was not observed after about 14.5 days post coitum in the embryo.
      In the adult mouse, SM 22 promoter activity persisted in the smooth muscle cells
      of the arteries and was still notably absent from other smooth muscles, despite
      the ubiquitous presence of the endogenous SM 22 protein. These findings on the
      transcriptional activity of a smooth muscle promoter in vivo reveal the existence
      of different differentiation programmes for smooth muscle cells in the veins and
      the arteries and raise the expectation of a further subdivision of programmes
      among the visceral muscles.

PMID- 8756288
TI  - Inhibition of Xbra transcription activation causes defects in mesodermal
      patterning and reveals autoregulation of Xbra in dorsal mesoderm.
AB  - The Brachyury (T) gene is required for formation of posterior mesoderm and for
      axial development in both mouse and zebrafish embryos. In this paper, we first
      show that the Xenopus homologue of Brachyury, Xbra, and the zebrafish homologue,
      no tail (ntl), both function as transcription activators. The activation domains
      of both proteins map to their carboxy terminal regions, and we note that the
      activation domain is absent in two zebrafish Brachyury mutations, suggesting that
      it is required for gene function. A dominant-interfering Xbra construct was
      generated by replacing the activation domain of Xbra with the repressor domain of
      the Drosophila engrailed protein. Microinjection of RNA encoding this fusion
      protein allowed us to generate Xenopus and zebrafish embryos which show striking
      similarities to genetic mutants in mouse and fish. These results indicate that
      the function of Brachyury during vertebrate gastrulation is to activate
      transcription of mesoderm-specific genes. Additional experiments show that Xbra
      transcription activation is required for regulation of Xbra itself in dorsal, but
      not ventral, mesoderm. The approach described in this paper, in which the DNA
      binding domain of a transcription activator is fused to the engrailed repressor
      domain, should assist in the analysis of other Xenopus and zebrafish
      transcription factors.

PMID- 8756289
TI  - The germ line regulates somatic cyst cell proliferation and fate during
      Drosophila spermatogenesis.
AB  - Spermatogenesis relies on the function of germ-line stem cells, as a continuous
      supply of differentiated spermatids is produced throughout life. In Drosophila,
      there must also be somatic stem cells that produce the cyst cells that accompany
      germ cells throughout spermatogenesis. By lineage tracing, we demonstrate the
      existence of such somatic stem cells and confirm that of germ-line stem cells.
      The somatic stem cells likely correspond to the ultrastructurally described cyst
      progenitor cells. The stem cells for both the germ-line and cyst lineage are
      anchored around the hub of non-dividing somatic cells located at the testis tip.
      We then address whether germ cells regulate the behavior of somatic hub cells,
      cyst progenitors and their daughter cyst cells by analyzing cell proliferation
      and fate in testes in which the germ line has been genetically ablated. Daughter
      cyst cells, which normally withdraw from the cell cycle, continue to proliferate
      in the absence of germ cells. In addition, cells from the cyst lineage switch to
      the hub cell fate. Male-sterile alleles of chickadee and diaphanous, which are
      deficient in germ cells, exhibit similar cyst cell phenotypes. We conclude that
      signaling from germ cells regulates the proliferation and fate of cells in the
      somatic cyst lineage.

PMID- 8756290
TI  - Roles of cell-autonomous mechanisms for differential expression of region
      specific transcription factors in neuroepithelial cells.
AB  - Although a number of genes have been found to have restricted expression domains
      in the embryonic forebrain and midbrain, it remains largely unknown how the
      expression of these genes is regulated at the cellular level. In this study, we
      explored the mechanisms for the differential expression of region-specific
      transcription factors in neuroepithelial cells by using both primary and
      immortalized neuroepithelial cells from the rat brain at embryonic day 11.5. We
      found that differential expression patterns of Pax-3, Pax-5, Pax-6, Dlx-1, Dlx-2,
      Emx2, Otx1 and Dbx observed in vivo were maintained even when the cells were
      isolated and cultured in vitro, free from environmental influences. Furthermore,
      in response to Sonic hedgehog, which is a major inductive signal from the
      environment for regional specification, neuroepithelial cells that maintain
      distinct regional identities expressed different sets of ventral-specific genes
      including Islet-1, Nkx-2.1 and Nkx-2.2. These results suggest that certain cell
      autonomous mechanisms play important roles in regulating both environmental
      signal-dependent and -independent expression of region-specific genes. Thus, we
      propose that use of the in vitro culture systems we describe in this study
      facilitates the understanding of regulatory mechanisms of region-specific genes
      in neuroepithelial cells.

PMID- 8756291
TI  - The intracellular deletions of Delta and Serrate define dominant negative forms
      of the Drosophila Notch ligands.
AB  - We examined the function of the intracellular domains of the two known Drosophila
      Notch ligands, Delta and Serrate, by expressing wild-type and mutant forms in the
      developing Drosophila eye under the sevenless promoter. The expression of
      intracellularly truncated forms of either Delta (sev-DlTM) or Serrate (sev-SerTM)
      leads to extra photoreceptor phenotypes, similar to the eye phenotypes associated
      with loss-of-function mutations of either Notch or Delta. Consistent with the
      notion that the truncated ligands reduce. Notch signalling activity, the eye
      phenotypes of sev-DlTM and sev-SerTM are enhanced by loss-of-function mutations
      in the Notch pathway elements, Notch, Delta, mastermind, deltex and groucho, but
      are suppressed by a duplication of Delta or mutations in Hairless, a negative
      regulator of the pathway. These observations were extended to the molecular level
      by demonstrating that the expression of Enhancer of split m delta, a target of
      Notch signalling, is down-regulated by the truncated ligands highly expressed in
      neighbouring cells. We conclude that the truncated ligands act as antagonists of
      Notch signalling.

PMID- 8756292
TI  - Hoxb-13: a new Hox gene in a distant region of the HOXB cluster maintains
      colinearity.
AB  - The Hox genes are involved in patterning along the A/P axes of animals. The
      clustered organization of Hox genes is conserved from nematodes to vertebrates.
      During evolution, the number of Hox genes within the ancestral complex increased,
      exemplified by the five-fold amplification of the AbdB-related genes, leading to
      a total number of thirteen paralogs. This was followed by successive duplications
      of the cluster to give rise to the four vertebrate HOX clusters. A specific
      subset of paralogs was subsequently lost from each cluster, yet the composition
      of each cluster was likely conserved during tetrapod evolution. While the HOXA,
      HOXC and HOXD clusters contain four to five AbdB-related genes, only one gene
      (Hoxb-9) is found in the HOXB complex. We have identified a new member of paralog
      group 13 in human and mouse, and shown that it is in fact Hoxb-13. A combination
      of genetic and physical mapping demonstrates that the new gene is found approx.
      70 kb upstream of Hoxb-9 in the same transcriptional orientation as the rest of
      the cluster. Despite its relatively large distance from the HOX complex, Hoxb-13
      exhibits temporal and spatial colinearity in the main body axis of the mouse
      embryo. The onset of transcription occurs at E9.0 in the tailbud region. At later
      stages of development, Hoxb-13 is expressed in the tailbud and posterior domains
      in the spinal cord, digestive tract and urogenital system. However, it is not
      expressed in the secondary axes such as the limbs and genital tubercle. These
      results indicate that the 5' end of the HOXB cluster has not been lost and that
      at least one member exists and is highly conserved among different vertebrate
      species. Because of its separation from the complex, Hoxb-13 may provide an
      important system to dissect the mechanism(s) responsible for the maintenance of
      colinearity.

PMID- 8756293
TI  - Transient release of calcium from inositol 1,4,5-trisphosphate-specific stores
      regulates mouse preimplantation development.
AB  - Inositol 1,4,5-trisphosphate can regulate growth and differentiation by
      modulating the release of intracellular Ca2+ in a variety of cellular systems,
      and it is involved in oocyte activation. Recent studies suggest that mammalian
      preimplantation development may also be regulated by the release of Ca2+ from
      intracellular stores. The rate of cavitation and cell division was accelerated
      after a transient elevation of intracellular Ca2+ levels was induced in morulae
      by exposure to ethanol or ionomycin. Embryos exposed to BAPTA-AM, a chelator of
      intracellular Ca2+, exhibited a brief dose-dependent reduction in basal Ca2+
      levels, a temporal inhibition of ionophore-induced Ca2+ signalling and a
      subsequent delay in blastocoel formation. BAPTA-AM at 0.5 microM did not
      significantly alter the basal intracellular calcium level, but chelated Ca2+ that
      was released after ethanol exposure and thereby attenuated the ethanol-induced
      acceleration of cavitation. BAPTA-AM also inhibited cell division to the 16-cell
      stage in a dose-dependent manner, which correlated with the inhibition of
      cavitation. Thimerosal and inositol 1,4,5-trisphosphate significantly elevated
      the intracellular Ca2+ concentration in mouse morula-stage embryos, providing
      evidence for the existence of inositol 1,4,5-trisphosphate-sensitive Ca2+ stores.
      Although caffeine failed to release intracellular Ca2+, ryanodine induced a small
      biphasic release of Ca2+, suggesting that ryanodine-sensitive Ca2+ stores may
      also exist in mouse embryos. Morulae exposed to the calmodulin inhibitor W-7
      exhibited a dose-dependent delay in blastocoel formation. A 4 hour exposure to 10
      microM W-7 did not significantly alter cavitation, but attenuated the ionophore
      induced stimulation of blastocoel formation. This finding suggests that the
      developmental effects produced through Ca2+ signalling are mediated by
      calmodulin. Our results demonstrate that Ca2+ release in mouse morulae occurs
      predominantly through the inositol 1,4,5-trisphosphate receptor, and that
      alteration of intracellular Ca2+ levels can accelerate or delay embryonic growth
      and differentiation, providing a mechanistic link between the regulation of
      oocyte and embryonic development.

PMID- 8756294
TI  - Insulin-like growth factor-I stimulates neurogenesis in chick retina by
      regulating expression of the alpha 6 integrin subunit.
AB  - Insulin-like growth factor I (IGF-I) strongly stimulates the generation of
      differentiated neurons in cultures of neuroepithelial cells of the embryonic
      chick neural retina in the presence of a laminin-1 tissue culture substrate.
      Treatment of cultured neuroepithelial cells with IGF-I rapidly up-regulated the
      mRNA coding for the alpha 6 integrin subunit whereas specific reduction of alpha
      6 subunit levels by treatment with an alpha 6 integrin antisense oligonucleotide
      resulted in reduced neuronal differentiation in vitro. Although IGF-I
      immunoreactivity is seen throughout the neural retina, expression of IGF-I mRNA
      is confined to the pigment epithelium during the period of neurogenesis in vivo.
      Neutralization of the endogenous IGF-I with a blocking antibody down-regulated
      levels of alpha 6 integrin mRNA and reduced the production of differentiated
      retinal neurons in vivo. These data indicate a role for IGF-I in the generation
      of retinal neurons mediated by the interaction of laminin with its alpha 6
      integrin subunit-containing receptor.

PMID- 8756295
TI  - Reversal of cell fate determination in Caenorhabditis elegans vulval development.
AB  - In Caenorhabditis elegans, the fates of the multipotent vulval precursor cells
      (VPCs) are specified by intercellular signals. The VPCs divide in the third
      larval stage (L3) of the wild type, producing progeny of determined cell types.
      In lin-28 mutants, vulva development is similar to wild-type vulva development
      except that it occurs precociously, in the second larval stage (L2).
      Consequently, when lin-28 hermaphrodites temporarily arrest development at the
      end of L2 in the dauer larva stage, they have partially developed vulvae
      consisting of VPC progeny. During post-dauer development, these otherwise
      determined VPC progeny become reprogrammed back to the multipotent, signal
      sensitive state of VPCs. Our results indicate that VPC fate determination by
      intercellular signals is reversible by dauer larva developmental arrest and post
      dauer development.

PMID- 8756296
TI  - Stage-specific accumulation of the terminal differentiation factor LIN-29 during
      Caenorhabditis elegans development.
AB  - The Caenorhabditis elegans gene lin-29 is required for the terminal
      differentiation of the lateral hypodermal seam cells during the larval-to-adult
      molt. We find that lin-29 protein accumulates in the nuclei of these cells,
      consistent with its predicted role as a zinc finger transcription factor. The
      earliest detectable LIN-29 accumulation in seam cell nuclei is during the last
      larval stage (L4), following the final seam cell division, which occurs during
      the L3-to-L4 molt. LIN-29 accumulates in all hypodermal nuclei during the L4
      stage. The time of LIN-29 appearance in the hypodermis is controlled by the
      heterochronic gene pathway: LIN-29 accumulates in the hypodermis abnormally
      early, during the third larval stage, in loss-of-function lin-14, lin-28 and lin
      42 mutants, and fails to accumulate in hypodermis of lin-4 mutants. LIN-29 also
      accumulates stage-specifically in the nuclei of a variety of non-hypodermal cells
      during development. Its accumulation is dependent upon the upstream heterochronic
      genes in some, but not all, of these non-hypodermal cells.

PMID- 8756298
TI  - Integrin alpha 6 expression is required for early nervous system development in
      Xenopus laevis.
AB  - The integrin alpha 6 subunit pairs with both the beta 1 and beta 4 subunits to
      form a subfamily of laminin receptors. Here we report the cDNA cloning and
      primary sequence for the Xenopus homologue of the mammalian integrin alpha 6
      subunit. We present data demonstrating the spatial and temporal expression of
      alpha 6 mRNA and protein during early development. Initially, alpha 6 transcripts
      are expressed in the dorsal ectoderm and future neural plate at the end of
      gastrulation. Later in development, alpha 6 mRNAs are expressed in a variety of
      neural derivatives, including the developing sensory placodes (otic and
      olfactory) and commissural neurons within the neural tube. Integrin alpha 6 is
      also expressed in the elongating pronephric duct as well as a subset of the
      rhombencephalic neural crest, which will form the Schwann cells lining several
      cranial nerves (VII, VIII and X). In vivo expression of an alpha 6 antisense
      transcript in the animal hemisphere leads to a reduction in alpha 6 protein
      expression, a loss of adhesion to laminin, and severe defects in normal
      development. In 35% of cases, reduced levels of alpha 6 expression result in
      embryos that complete gastrulation normally but arrest at neurulation prior to
      the formation of the neural plate. In an additional 22% of cases, embryos develop
      with severe axial defects, including complete loss of head or tail structures. In
      contrast, overexpression of the alpha 6 subunit by injection of full-length mRNA
      has no apparent effect on embryonic development. Co-injection of antisense and
      sense plasmid constructs results in a partial rescue of the antisense-generated
      phenotypes. These data indicate that the integrin alpha 6 subunit is critical for
      the early development of the nervous system in amphibians.

PMID- 8756297
TI  - Oligodendrocytes and their precursors require phosphatidylinositol 3-kinase
      signaling for survival.
AB  - Signal transduction in response to several growth factors that regulate
      oligodendrocyte development and survival involves the activation of
      phosphatidylinositol 3-kinase, which we detect in oligodendrocytes and their
      precursors. To investigate the role of this enzyme activity, we analyzed cell
      survival in cultures of oligodendrocytes treated with wortmannin or LY294002, two
      potent inhibitors of phosphatidylinositol 3-kinase. Cell survival was inhibited
      by 60-70% in these cultures within 24 hours, as quantitated by a tetrazolium
      staining assay for viable cells and by measurement of DNA content. Similar
      results were obtained with oligodendrocyte precursor cells. Nuclei of the dying
      cells contained fragmented DNA, as revealed by terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end-labeling assays, indicating that the
      cells were dying by apoptosis. Moreover, a significant increase in the number of
      cells with fragmented nuclear DNA was detected as early as 4 hours, well before
      any significant differences could be detected in glucose transport or cell
      viability. Exogenous addition of insulin-like growth factor-I, neurotrophin-3,
      platelet-derived growth factor, basic fibroblast growth factor, ciliary
      neurotrophic factor, N-acetyl cysteine, vitamin C, vitamin E, progesterone or
      serum did not prevent cell death in the presence of wortmannin or LY294002. These
      findings indicate that survival of oligodendrocytes and their precursors depends
      on a phosphatidylinositol 3-kinase mediated signaling pathway. Inhibition of this
      critical enzyme activity induces apoptotic cell death, even in the presence of
      exogenous growth factors or serum.

PMID- 8756299
TI  - Inhibition of floor plate differentiation by Pax3: evidence from ectopic
      expression in transgenic mice.
AB  - The Pax genes containing a complete paired-type homeobox are expressed in
      restricted dorsoventral domains of the undifferentiated neuroepithelium. Their
      expression respond to signals that pattern the neural tube and which emanate from
      the notochord, floor plate and overlying ectoderm. In order to determine whether
      the dorsally restricted Pax3 gene can influence the fate of cells within the
      neural tube, we produced transgenic mice overexpressing Pax3 in the entire neural
      tube under the Hoxb-4 promoter/region A enhancer. In two distinct transgenic
      mouse lines, we observed embryos with abnormal limb, eye, brain and neural tube
      development. Expression of Pax3 was not sufficient to dorsalize cells from the
      ventral intermediate zone, which still expressed ventral markers. However, in
      these embryos, expression of Pax3 at the ventral midline was associated with the
      absence of floor plate differentiation. Under these conditions, motor neurons
      still differentiated in the ventral spinal cord, although in fewer numbers.

PMID- 8756300
TI  - Juvenile hormone: the status of its "status quo" action.
AB  - Juvenile hormone (JH) allows larval molting in response to ecdysteroids but
      prevents the switching of gene expression necessary for metamorphosis. I first
      review our efforts to isolate the nuclear receptor for JH in the larval epidermis
      of Manduca sexta using photoaffinity analogs and our recent findings that the
      molecule isolated does not bind JH I with high affinity. The reported apparent
      high affinity binding of JH I by the recombinant 29 kDa protein (rJP29) was
      artifactual due to the presence of contaminating esterases. Purified rJP29 bound
      little detectable JH I, but its binding of the photoaffinity analog was prevented
      by JH I as well as other isoprenoids, indicating a low affinity for these
      compounds. Our recent studies focus on the effects of JH on the early molecular
      events induced by 20-hydroxyecdysone (20E). Culture of day 2 5th larval epidermis
      with 10(-6)M 20E for 24 h caused first pupal commitment, then the onset of the
      predifferentiative events necessary for pupation. Biphasic increases in the mRNAs
      of the two isoforms of the ecdysone receptor (EcR-A and EcR-B1) and of E75A, an
      ecdysteroid-induced transcription factor, coincided with these two phases. The
      mRNAs for Ultraspiracle (USP) and the metamorphosis-specific Broad-Complex (BR-C)
      increased only during the second phase. The presence of JH had no effect on the
      initial increases in EcR mRNAs but caused an increased accumulation of E75A mRNA.
      This JH also prevented the later changes in EcR, USP, and BR-C mRNAs. Thus, JH
      influences only certain of the early actions of 20E which then result in its
      preservation of the "status quo."

PMID- 8756301
TI  - Role of allatostatins in the regulation of juvenile hormone synthesis.
AB  - The identification of neuropeptides that inhibit juvenile hormone (JH) synthesis
      by the corpora allata (CA) has verified the existence of these allatostatins,
      which, from much experimental evidence, have long been postulated to occur. It
      also makes possible new approaches for studying the role of allatostatins in the
      regulation of JH synthesis. Allatostatins, localized immunocytochemically, occur
      in lateral neurosecretory cells of the brain that innervate the CA. Presumably
      their effect on the CA results from the release of allatostatins at these nerve
      endings. Allatostatins also occur in the hemolymph in cockroaches and have been
      shown to act on the CA through this pathway. The ability of allatostatins to
      inhibit CA depends not only on the concentration of the peptides but also on the
      sensitivity of the CA to them. Male Diploptera punctata were treated with JH
      analog following denervation of CA and implanted with a previtellogenic or
      vitellogenic ovary or injected with saline. Animals implanted with a vitellogenic
      ovary, compared to the previtellogenic ovary or saline, showed significantly
      increased JH synthesis by their CA and a reduced amount of allatostatin in the
      hemolymph. The denervated CA from these JH analog treated animals, following
      implantation with a previtellogenic and vitellogenic ovary, showed a tendency
      toward increased and decreased sensitivity, respectively, to a given dose of
      allatostatin in vitro compared to those from saline injected controls.
      Experiments such as these suggest that changes in release of allatostatins and in
      sensitivity of CA to them could be postulated to be major factors regulating JH
      synthesis in the cockroach.

PMID- 8756302
TI  - Sex-peptide activates juvenile hormone biosynthesis in the Drosophila
      melanogaster corpus allatum.
AB  - Mating elicits two well-defined reactions in sexually matured females of many
      insects: reduction of receptivity and increased oviposition. These post-mating
      responses have been shown to be induced by factors synthesized in the
      reproductive tract of the adult male and transferred in the seminal fluid to the
      female during copulation. One of these factors, named sex-peptide (SP), has been
      identified in Drosophila melanogaster. Using an in vitro radiochemical assay, we
      show that synthetic sex-peptide considerably activates juvenile hormone III
      bisepoxide (JHB3) synthesis in corpus allatum (CA) excised from Days 3 and 4 post
      eclosion virgin females. Base levels are significantly lower at emergence (Day 0)
      than on subsequent days, and only weak stimulation is obtained on Day 1, while
      none is obtained on Day 2, where maximal basal synthesis occurs. The CA of mated
      females cannot be stimulated further for at least 7 days, but regain
      responsiveness by Day 10 after mating. Synthesis of JHB3 stimulated by SP in
      vitro persists for at least 4 h after removal of the peptide. Development of
      responsiveness of the CA to SP in vitro is compared with development of the post
      mating reactions of sex-peptide injected virgin females. Our results suggest that
      the CA is a direct target for SP in vivo and that sexual maturity is established
      separately for the two post-mating reactions.

PMID- 8756303
TI  - Biochemistry of proteins that bind and metabolize juvenile hormones.
AB  - A diverse group of proteins has evolved to bind and metabolize insect juvenile
      hormones (JHs). Synthetic radiolabeled JHs and their photoaffinity analogs have
      enabled us to isolate and characterize JH binding proteins (JHBPs), a putative
      nuclear JH receptor, JH esterases (JHEs), JH epoxide hydrolases (JHEHs), and
      methyl farnesoate binding proteins (MFBPs). Highlights of recent progress on
      structural characterization of JHBPs and JHEHs of two lepidopterans will be
      described. Efforts to identify MFBPs of penaeid shrimp will be discussed, and the
      discovery of a possible vertebrate JHBP will be presented.

PMID- 8756304
TI  - Overview of the regulation of metamorphosis-associated genes in Trichoplusia ni.
AB  - A review is presented of our ongoing research program on the regulation of
      metamorphosis-associated proteins in Trichoplusia ni. Toward the identification
      of mechanisms by which juvenile hormone (JH) regulates expression of
      metamorphosis-associated proteins, we have identified a protein that is induced
      by JH (juvenile hormone esterase) and a related esterase that is not JH
      inducible. We have also identified three hexamerins that are suppressible by JH,
      and one hexamerin that is not JH-suppressible. Expression of the hexamerins is
      regulated at the transcriptional, translational, and posttranslational levels in
      T. ni. The rate of transcription of the JH esterase gene increases at the time of
      the prepupal peak in JH, and exogenous application of JH can cause, within 3 h,
      the rate of transcription to be the markedly elevated above normal. Using in
      vitro functional transcription assay, cell line transfection functional assay,
      and preliminary DNase I hypersensitive site mapping we were able to identify the
      functional TATA box and transcription start sites of JH-sensitive genes. These
      methods were also observed to be powerful in the detection of regulatory DNA
      motifs involved in the modulation of transcriptional activity constitutively
      imparted by a core promoter. The experimental systems described here will also be
      effective in identifying those components through which JH regulatory effects are
      mediated. Should JH act on the genes in a primary manner, then the transcription
      factor mediating that action may be the (a) JH receptor. Should the JH action be
      in a secondary manner, then the transcription factor(s) whose activity at the JHE
      gene is regulated by JH will provide the tool to track back to the location and
      nature of the primary JH action.

PMID- 8756305
TI  - Cloning of a putative juvenile hormone-responsive storage protein gene from the
      tobacco budworm, Heliothis virescens.
AB  - A cDNA clone with 78% amino acid identity to a basic juvenile hormone (JH)
      suppressible hemolymph protein from the cabbage looper, Trichoplusia ni, was
      isolated from the tobacco budworm, Heliothis virescens. This clone was obtained
      upon screening a cDNA library derived from larval fat body of a pesticide
      resistant strain of H. virescens with a cDNA probe for Drosophila melanogaster
      glutathione S-transferase. By comparison with other insect storage proteins, this
      clone was predicted to be part of an approximately 2,300 nucleotide (nt) cDNA, of
      which 691 nt were isolated and sequenced. The partial cDNA clone hybridizes to a
      RNA of approximately 2,370 nt in H. virescens. Treatment with a juvenoid (2-[1
      methyl-2-(4-phenoxyphenoxy)ethoxy] pyridine; pyriproxifen) leads to a decrease in
      RNA levels of this putative hemolymph storage protein in early fifth stadium
      larvae of H. virescens, prior to commitment. In contrast, treatment in late fifth
      stadium (after commitment to pupal development) leads to an increase in the RNA
      level of this JH-responsive gene. This is the first report of both induction and
      suppression of storage protein RNA levels in the same stadium. We have given this
      gene the designation Hv-SP4 (H. virescens, storage protein 4; accession no.
      U48594). Genetic segregation analysis of restriction fragment length
      polymorphisms (RFLPs) defined by Hv-SP4 has shown that it is the product of a
      single-copy, Mendelian, autosomal gene.

PMID- 8756306
TI  - Dopaminergic control of corpora allata activity in the larval tobacco hornworm,
      Manduca sexta.
AB  - The corpora allata (CA) of insects are innervated by axons of non-neurosecretory
      cerebral neurons, and of the various known neurotransmitters in the brain of the
      tobacco hornworm, Manduca sexta, only dopamine is detected in the CA by
      electrochemical detection HPLC. This neurotransmitter stimulates the biosynthetic
      activity of the CA in vitro for the first 2 days of the last larval stadium, but
      inhibits CA from day 3 through day 6, the beginning of the prepupal period.
      Stimulation of JH synthesis has previously been linked with an increase in the
      production of cyclic AMP (cAMP) in the CA, and dopamine stimulates the adenylyl
      cyclase system of CA from larvae early in the fifth stadium, while on day 6, its
      effect is inhibitory. These results suggest: (1) the existence in the CA of both
      D1- and D2-like dopamine receptors, which in vertebrates stimulate and inhibit,
      respectively, adenylyl cyclase; and (2) the developmental control of their
      expression. A potent D1 agonist, (+/-)-SKF 82958-HBr, did not stimulate JH
      biosynthesis by day 0 CA as expected, but appeared to inhibit it at a
      concentration of 10(-5)M. Thus the apparent D1-like receptor in Manduca CA may be
      pharmacologically distinct from vertebrate D1 receptors. The existence of D2-like
      receptors is supported by the finding that a vertebrate D2 receptor agonist, (+/
      ) PPHT-HCl, and an antagonist, eticlopride, have the predicted effects on JH acid
      biosynthesis and cAMP production by day 6 Manduca CA. However, the D1 agonist
      also significantly reduces JH acid biosynthesis and cAMP production, indicating
      that while the Manduca D2-like receptor is pharmacologically similar to the
      vertebrate D2, it shares some characteristics with D1 receptors. The
      developmental regulation of these receptors by ecdysteroids is suggested by the
      fact that when day 0 larvae are treated in vivo with exogenous ecdysone:20
      hydroxyecdysone, the biosynthetic activity of the CA in vitro 24 h later is no
      longer stimulated by dopamine.

PMID- 8756307
TI  - Mechanism of action and cloning of epoxide hydrolase from the cabbage looper,
      Trichoplusia ni.
AB  - The majority of the JH III epoxide hydrolase activity in last stadium day 3 (gate
      1) wandering Trichoplusia ni was membrane bound with approximately 9% of the
      activity found in the cytosol. Both the microsomal and cytosolic JH epoxide
      hydrolases were stable, retaining 30% of their original activity after incubation
      at 4 degrees C for 15 days. 18O-labeled water underwent enzyme catalyzed
      regioselective addition to the least substituted C10 position of JH III. In
      multiple turnover reactions with JH epoxide hydrolase in 97.9% 18O-labeled water,
      only 91.3% 18O incorporation was observed. This is consistent with an SN2
      reaction likely involving a carboxylate in the active site of JH epoxide
      hydrolase. The DNA amplification cloning of a fragment of a putative T. ni
      epoxide hydrolase is reported. The deduced amino acid sequence shares 67%
      similarity to the rat microsomal epoxide hydrolase.

PMID- 8756308
TI  - Altered hexamerin regulation in prepupal Trichoplusia ni pseudoparasitized by
      Chelonus sp. near curvimaculatus.
AB  - Adult female wasps of species in the subfamily Cheloninae inject an egg, venom,
      polydnavirus and other materials into the host egg during oviposition. Hosts then
      exhibit precocious expression of the metamorphic developmental program, but then
      further development by the precocious prepupa is suppressed. These effects occur
      in truly parasitized hosts (those that contain a live endoparasite larva) as well
      as in pseudoparasitized hosts (that do not contain a live endoparasite). We
      report here that during the precocious prepupal stage, the hexamerins BJHSP1 and
      BJHSP2 persist in the hemolymph of pseudoparasitized hosts, whereas in normal
      larvae these proteins are cleared from the hemolymph in response to the normal
      surge in prepupal ecdysteroids. Northern blot analysis of poly(A) RNA showed that
      the basis for this persistence is not an abnormally high abundance of the
      transcripts on the day following wandering in pseudoparasitized larvae. Nor is
      the source of the hexamerins the parasite larva, for it is missing from the
      pseudoparasitized hosts. The hypothesis that the persistence is due to a
      suppressed titer of ecdysteroids in pseudoparasitized hosts (reported earlier:
      [jones et al., Arch Insect Biochem Physiol 21:155 (1992)] was tested by use of a
      large size variant of pseudoparasitized hosts in which the prepupal ecdysteroid
      titer is partially restored by endogenous ecdysteroid production. In such
      pseudoparasitized prepupae, the two hexamerins were cleared from the hemolymph on
      the day following host wandering behavior, as in normal larvae. Thus, the
      regulatory basis of the persistence of the hexamerins BJHSP1 and BJHSP2 in the
      hemolymph of pseudoparasitized hosts appears to be at the posttranslational
      level, with suppression of the prepupal ecdysteroid titer causing omission of the
      normal trigger for fat body uptake of the hexamerins.

PMID- 8756309
TI  - Cosmic influences on the expression of a specific gene in the Colorado potato
      beetle: the diapause protein 1 gene.
AB  - Diapause protein 1 from the Colorado potato beetle, Leptinotarsa decemlineata,
      belongs to the family of insect storage hexamers. The protein accumulates in the
      hemolymph of last instar larvae and in adults reared under short-day (diapause
      inducing) conditions. The protein disappears during metamorphosis, but remains in
      the hemolymph during diapause. The gene which encodes diapause protein 1
      encompasses about 9 kb of chromosomal DNA and is composed of 5 exons, separated
      by 4 introns. The gene is expressed in last-instar larvae and in adults reared
      under short-day conditions. The messenger RNA for diapause protein 1 occurs only
      in the fat body. Gene expression is higher in the fat body from short-day adults
      than from last-instar larvae. Transcription is suppressed after topical
      application of pyriproxyfen, a JH-analog. The messenger RNA of the protein
      (approximately 2.3 kb) contains genetic information of a pre-protein of 702 amino
      acids, including a signal peptide of 17 amino acids and protein of 685 residues.
      The function of diapause protein 1 is unknown, but it is utilized during post
      diapause development, probably for regeneration of the flight muscles.

PMID- 8756310
TI  - Fenoxycarb and thyroid hormones have JH-like effects on the follicle cells of
      Locusta migratoria in vitro.
AB  - Earlier work had shown that JH acts on the membrane of the follicle cell of
      Locusta migratoria, bringing about a rapid reduction in volume which can be
      detected in vitro by measuring the increase in optical path difference using
      quantitative interference microscopy. The juvenoid fenoxycarb, a phenoxyphenyl
      derivative, is unrelated in structure to the juvenile hormones (which are
      derivatives of farnesoic acid), but it also caused a reduction in volume of the
      cells in vitro as measured by an increase in the optical path difference. The
      vertebrate hormone thyroxine, and thyronine, the non-iodinated derivative of
      thyroxine, also phenoxy phenyl compounds, evoked a response like fenoxycarb. The
      effect of thyroxine was abolished by ouabain, which inhibits Na+/K+ ATPase, the
      effector molecule for JH, and inhibited by ethoxyzolamide which inhibits the
      binding of JH to a putative membrane receptor. Triiodothyronine, the effective
      vertebrate hormone, acted at a lower threshold and optimum concentration, and had
      a greater magnitude of effect than the other compounds tested. These facts
      suggest that these phenoxyphenyl compounds are JH agonists and that the membrane
      receptor for JH may resemble a possible membrane receptor for thyroxine.

PMID- 8756311
TI  - Genetic evidence that mutants of the methoprene-tolerant gene of Drosophila
      melanogaster are null mutants.
AB  - The Methoprene-tolerant (Met) mutation of Drosophila melanogaster results in
      resistance to juvenile hormone (JH) or JH analogs and appears to alter JH
      reception during late larval development. Several alleles of Met have been
      recovered from methoprene selection screens after mutagenesis with ethyl
      methanesulfonate, X-rays, or transposable genetic elements. The phenotype of
      files carrying any of these alleles is similar-resistance to the toxic and
      morphogenetic effects of methoprene-but otherwise is essentially wild-type.
      Understanding the function of the Met gene requires that we know whether these
      alleles are hypomorphic, producing some functional gene product, or amorphic,
      producing no functional gene product. This determination was made by comparing
      the methoprene-resistance phenotype produced by representative Met alleles with
      that produced by a chromosome carrying a deficiency that deletes the Met gene.
      The level of resistance to either the toxic or the morphogenetic effect of
      methoprene was similar among files heterozygous for either the deficiency
      chromosome or for any of the alleles. The results provide genetic evidence that
      the Met alleles recovered to date are amorphic and suggest that the Met gene may
      not be mutable to a more severe Met allele that affects the viability,
      development, or reproduction of the flies.

PMID- 8756312
TI  - Activity of novel juvenoids on arthropods of veterinary importance.
AB  - Different juvenile hormone mimics were compared regarding their efficacy against
      larval and pupal stages of the diptera Aedes aegypti, Musca domestica, and
      Lucilia cuprina as well as the cat flea Ctenocephalides felis. Structure-activity
      relationship of a series of new diphenylethers was analyzed and compared to
      juvenoids like methoprene, hydroprene, and fenoxycarb. Selected compounds were
      taken for a competition binding assay and their effect on JH-degradation by
      esterases was examined. The results indicate that neither high affinity to JH
      binding proteins nor interference with JH breakdown are responsible for the
      extraordinary efficacy of the diphenylethers investigated. Two superior
      diphenylethers, however, proved to be more resistant to UV-radiation than
      methoprene.

PMID- 8756313
TI  - Projuvenoids: synthesis and biological evaluation of sulfenylated, sulfinylated,
      and sulfonylated carbamates.
AB  - Applying the proinsecticide principle developed earlier for neurotoxic carbamate
      insecticides, a series of new N-sulfenylated, N-sulfinylated, and N-sulfonylated
      derivatives of fenoxycarb were synthesized and evaluated for juvenile hormone
      mimicking activity. Laboratory evaluations of the compounds using Pieris
      brassicae and Sitophilus oryzae, as well as field experiments using Bemisia
      tabaci, showed that several symmetrical biscarbamates with either a sulfenyl or
      sulfinyl bridge possessed higher activity than the parent carbamate. From the
      unsymmetrical compounds containing biologically inert derivatizing moieties, one
      of the sulfenylated biscarbamates also showed improved activity against P.
      brassicae. The changes in the biological activity of the sulfur-containing
      derivatives compared to that of the parent compound are attributed to the
      modified physicochemical characteristics, i.e., increased lipophilicity
      facilitating penetration, transport, as well as protection of the compound from
      metabolism.

PMID- 8756315
TI  - Peptidergic transmission: from morphological correlates to functional
      implications.
AB  - Like non-peptidergic transmitters, neuropeptides and their receptors display a
      wide distribution in specific cell types of the nervous system. The peptides are
      synthesized, typically as part of a larger precursor molecule, on the rough
      endoplasmic reticulum in the cell body. In the trans-Golgi network, they are
      sorted to the regulated secretory pathway, packaged into so-called large dense
      core vesicles, and concentrated. Large dense-core vesicles are preferentially
      located at sites distant from active zones of synapses. Exocytosis may occur not
      only at synaptic specializations in axonal terminals but frequently also at
      nonsynaptic release sites throughout the neuron. Large dense-core vesicles are
      distinguished from small, clear synaptic vesicles, which contain "classical'
      transmitters, by their morphological appearance and, partially, their biochemical
      composition, the mode of stimulation required for release, the type of calcium
      channels involved in the exocytotic process, and the time course of recovery
      after stimulation. The frequently observed "diffuse' release of neuropeptides and
      their occurrence also in areas distant to release sites is paralleled by the
      existence of pronounced peptide-peptide receptor mismatches found at the light
      microscopic and ultrastructural level. Coexistence of neuropeptides with other
      peptidergic and non-peptidergic substances within the same neuron or even within
      the same vesicle has been established for numerous neuronal systems. In addition
      to exerting excitatory and inhibitory transmitter-like effects and modulating the
      release of other neuroactive substances in the nervous system, several
      neuropeptides are involved in the regulation of neuronal development.

PMID- 8756316
TI  - Beta gamma-crystallin redux.

PMID- 8756317
TI  - Ras biology in atomic detail.

PMID- 8756318
TI  - Looking for the DNA killer app.
AB  - The structural and functional properties of nucleic acids may form the basis for
      carrying out elementary and complex computational operations with biological
      molecules. A recent meeting on computing with DNA explored the potential of this
      approach.

PMID- 8756319
TI  - Aldose reductase: black sheep or skeleton in the cupboard?

PMID- 8756320
TI  - Ancestral beta gamma-crystallin precursor structure in a yeast killer toxin.

PMID- 8756321
TI  - Crystal structure of human estrogenic 17 beta-hydroxysteroid dehydrogenase
      complexed with 17 beta-estradiol.

PMID- 8756322
TI  - A specific structural interaction of Alzheimer's peptide A beta 1-42 with alpha 1
      antichymotrypsin.

PMID- 8756323
TI  - Structure of astacin with a transition-state analogue inhibitor.

PMID- 8756324
TI  - Picture story. Jellyroll boat.

PMID- 8756325
TI  - Inhibitory conformation of the reactive loop of alpha 1-antitrypsin.
AB  - The reactive site loop of the serpin family of serine proteinase inhibitors is
      flexible and can adopt a number of diverse conformations. A 2.9 A resolution
      structure of alpha 1-antitrypsin-the principal proteinase inhibitor in human
      plasma-shows the loop in a stable canonical conformation matching that found in
      all other families of serine proteinase inhibitors. This unexpected finding in
      the absence of loop insertion into the body of the molecule favours a two-stage
      mechanism of inhibition and provides a model for the heparin activation of
      antithrombin. The beta-pleated strand conformation of the loop also accounts for
      the polymerization of the serpins in disease and for their association with other
      beta-sheet structures, most notably the beta-amyloid of Alzheimer's disease.

PMID- 8756326
TI  - Proline scanning mutagenesis of a molten globule reveals non-cooperative
      formation of a protein's overall topology.
AB  - Small proteins generally fold cooperatively: disruption of significant parts of
      the folded structure leads to unfolding of the rest of the protein. We show here,
      using proline scanning mutagenesis, that the native-like tertiary fold of the
      alpha-lactalbumin (alpha-LA) molten globule is formed by the non-cooperative
      assembly of its constituent helices. In contrast to the drastic destabilizing
      effects of proline substitutions in cooperatively folded proteins, proline
      mutations in the molten globule appear to cause only individual helices to
      unfold, without significantly influencing the other helices or the overall
      topology. Thus, the key determinants of a protein's overall fold may not be of
      the all-or-none type.

PMID- 8756327
TI  - Structure-based design of a potent transition state analogue for TEM-1 beta
      lactamase.
AB  - The structure of the plasmid-mediated beta-lactamase TEM-1 has been solved in
      complex with a designed boronic acid inhibitor (1R)-1-acetamido-2-(3
      carboxyphenyl)ethane boronic acid at 1.7 A resolution. The boronate inhibitor was
      designed based on the crystallographic coordinates of the acyl-enzyme
      intermediate of TEM-1 bound to the substrate penicillin G. The boronate-TEM-1
      complex is highly ordered and defines a novel transition state analogue of the
      deacylation step in the beta-lactamase reaction pathway. The design principles of
      this highly effective inhibitor (Ki = 110 nM) and the resulting structural and
      mechanistic implications are presented.

PMID- 8756328
TI  - Structural basis of cyclin-dependent kinase activation by phosphorylation.
AB  - Cyclin-dependent kinase (CDK)-cyclin complexes require phosphorylation on the CDK
      subunit for full activation of their Ser/Thr protein kinase activity. The crystal
      structure of the phosphorylated CDK2-CyclinA-ATP gamma S complex has been
      determined at 2.6 A resolution. The phosphate group, which is on the regulatory T
      loop of CDK2, is mostly buried, its charge being neutralized by three Arg side
      chains. The arginines help extend the influence of the phosphate group through a
      network of hydrogen bonds to both CDK2 and cyclinA. Comparison with the
      unphosphorylated CDK2-CyclinA complex shows that the T-loop moves by as much as 7
      A, and this affects the putative substrate binding site as well as resulting in
      additional CDK2-CyclinA contacts. The phosphate group thus acts as a major
      organizing centre in the CDK2-CyclinA complex.

PMID- 8756329
TI  - Isolation of a local tertiary folding transition in the context of a globally
      folded RNA.
AB  - Binding of the Tetrahymena ribozyme's oligonucleotide substrate represents a
      local folding event in the context of a globally folded RNA. Substrate binding
      involves P1 duplex formation with the ribozyme's internal guide sequence to give
      an "open complex', followed by docking of the P1 duplex into tertiary
      interactions to give a "closed complex'. We have isolated the open complex as a
      thermodynamically stable species using a site-specific modification and high Na+
      concentrations. This has allowed characterization of P1 docking, which represents
      a folding transition between local secondary and local tertiary structure. P1
      docking is entropically driven, possibly accompanied by a release of bound water
      molecules. Strategies analogous to those described here can be used more
      generally to study local folding events in large structured RNAs and to explore
      the structural and energetic landscape for RNA folding.

PMID- 8756330
TI  - The dimeric DNA binding domain of the human papillomavirus E2 protein folds
      through a monomeric intermediate which cannot be native-like.
AB  - The dimeric DNA binding domain of the human papillomavirus E2 protein displays a
      two-state concerted unfolding and dissociation, with no detectable monomeric
      intermediate species accumulated at equilibrium. We investigated the kinetic
      folding mechanism of the dimeric domain using stopped-flow spectroscopic
      techniques and observed a fast forming monomeric intermediate, followed by a
      slower bimolecular reaction. Both phases involve secondary structure
      rearrangements of similar magnitude. Our results support a folding pathway in
      which the formation of an early monomeric intermediate, with characteristics of
      hydrophobic collapse, is followed by a bimolecular step encompassing association
      and folding. The interwoven folding topology of this particular type of dimeric
      beta-barrel found in the E2 DNA binding domain strongly suggests that any
      monomeric species formed could not be native-like.

PMID- 8756331
TI  - Novel mechanism for defective receptor binding of apolipoprotein E2 in type III
      hyperlipoproteinemia.
AB  - The defective binding of apolipoprotein (apo) E2 to lipoprotein receptors, an
      underlying cause of type III hyperlipoproteinemia, results from replacement of
      Arg 158 with Cys, disrupting the naturally occurring salt bridge between Asp 154
      and Arg 158. A new bond between Asp 154 and Arg 150 is formed, shifting Arg 150
      out of the receptor binding region. Elimination of the 154-150 salt bridge by
      site-directed mutagenesis of Asp 154 to Ala restored the receptor binding
      activity to near normal levels. The X-ray crystal structure of apoE2 Ala 154
      demonstrated that Arg 150 was relocated within the receptor binding region. Our
      results demonstrate that defective binding of apoE2 occurs by a novel mechanism
      of the replacement of one salt bridge with another.

PMID- 8756332
TI  - Ras/Rap effector specificity determined by charge reversal.
AB  - Members of the Ras subfamily of small GTP-binding proteins have been shown to be
      promiscuous towards a variety of putative effector molecules such as the protein
      kinase c-Raf and the Ral-specific guanine nucleotide exchange factor (Ral-GEF).
      To address the question of specificity of interactions we have introduced the
      mutations E30D and K31E into Rap and show biochemically, by X-ray structure
      analysis and by transfection in vivo that the identical core effector region of
      Ras and Rap (residues 32-40) is responsible for molecular recognition, but that
      residues outside this region are responsible for the specificity of the
      interaction. The major determinant for the switch in specificity is the opposite
      charge of residue 31--Lys in Rap, Glu in Ras--which creates a favourable
      complementary interface for the Ras-Raf interaction.

PMID- 8756333
TI  - A downstream AP-1 element regulates in vitro lung transcription from the human
      pulmonary surfactant protein B promoter.
AB  - We have used the human lung surfactant protein B (SP-B) gene as a template for in
      vitro transcription studies. Transcription factors were provided by nuclear
      extracts from a cultured line of human lung (type II-like) cells. Elements
      upstream of -50 had essentially no effect on the efficiency of the SP-B promoter
      in vitro. However, a deletion of the region from +8 to +8 reduced in vitro
      transcription by a factor of 10. The only factor whose binding was detected
      between +1 and +100 by footprinting, and between +12 and +38 by electrophoretic
      mobility shift analysis (EMSA), was a member of the AP-1 family. Mutation of 4 of
      7 bases of the AP-1 site reduced transcription two-fold and ablated the AP-1 EMSA
      binding complex observed on the SP-B downstream region (+12 to +38). Competition
      with unlabeled AP-1 consensus oligonucleotide abolished the downstream footprint
      over the AP-1 site. Thus, the SP-B promoter is one of a very small class of RNA
      polymerase II promoters that are strongly dependent in vitro on sequence elements
      downstream of the transcription start site, and, in this case, the AP-1 consensus
      element and surrounding sequences.

PMID- 8756334
TI  - Human Cart-1: structural organization, chromosomal localization, and functional
      analysis of a cartilage-specific homeodomain cDNA.
AB  - Homeoproteins control cell fates during development, specifying pattern formation
      and the ontogeny of specific tissues and organs in embryogenesis. Cart-1 cDNA was
      recently cloned from a rat chondrosarcoma tumor and it encodes a protein
      containing a paired-like homeodomain that is selectively expressed in cartilage
      during early chondrocyte differentiation. Here we report the molecular cloning of
      the human Cart-1 cDNA from a HeLa cervical carcinoma cDNA library. The human Cart
      1 cDNA sequence is 88% identical and the deduced amino acid sequence is 95%
      identical to the rat sequence, indicating that Cart-1 structure is highly
      conserved. Northern and reverse transcriptase polymerase chain reaction (RT-PCR)
      analysis revealed Cart-1 mRNA expression in HeLa cervical carcinoma cells and
      human cervical tissue, but Cart-1 mRNA was not detected in GH3 rat pituitary
      cells and murine 10T1/2 one-half fibroblast cells. The Cart-1 gene was localized
      to human chromosome 12 and regionally mapped to the 12q21.3-q22 by PCR analysis
      of rodent-X-human somatic cell hybrid DNA and the CEPH megabase-insert YAC DNA
      pools, respectively. The Holt-Oram syndrome, characterized by upper limb and
      atrial septal dysplasias, also maps to the 12q21.3-q22 region. Cotransfection
      studies show that Cart-1 inhibits the rat prolactin promoter and that this
      repression is mediated by footprint II, an AT-rich element that functions as an
      inhibitory site of prolactin gene expression in nonpituitary cells and which was
      used to clone Cart-1. Taken together, these data indicate that Cart-1 may also
      influence cervix development, identify a putative DNA binding site for Cart-1,
      and, begin to define its functional role as modulator of gene expression.

PMID- 8756335
TI  - Novel DNase I hypersensitive sites in the 3'-flanking region of the human c-myc
      gene.
AB  - DNase I hypersensitivity regions correlate with genetic regulatory loci and
      binding sites for sequence-specific DNA-binding proteins. We present data
      supporting the presence of novel DNase 1 hypersensitive sites (which we have
      designated sites VI-IX) in both the body of the human c-myc gene downstream from
      exon 2 and the 3'-flanking region of the c-myc gene in HL-60 cells. All of these
      novel DH sites are markedly decreased when HL-60 cells are treated with either
      dimethyl sulfoxide (DMSO) or retinoic acid. Moreover, a similar pattern of DNase
      I hypersensitive sites in this region of c-myc was present in MCF-7 human breast
      cancer cells growing in culture. Our results suggest a potential role for these
      sites in transcriptional regulation of the human c-myc gene.

PMID- 8756337
TI  - A "stealth" approach to inhibition of lymphocyte activation by oligonucleotide
      complementary to the putative G0/G1 switch regulatory gene G0S30/EGR1/NGFI-A.
AB  - The putative G0/G1 switch regulatory gene G0S30/EGR1/NFGI-A show increased
      expression shortly after adding concanavalin-A (ConA) to cultured T lymphocytes.
      However, it is reported that lymphocytes from mice in which the gene has been
      deleted proliferate normally in response to ConA. This suggests that G0S30
      expression is not critical for the response. Paradoxically, others report that
      proliferation of ConA-stimulated rat lymphocytes is inhibited by an antisense
      oligonucleotide complementary to G0S30. Because the G0S30 sequence is highly
      conserved between species, we used a similar oligonucleotide (differing by 1
      base) to show for humans that the response to ConA is also inhibited. However, no
      oligonucleotide-induced changes in the concentrations of G0S30 protein or mRNA
      are detectable. This suggests that the oligonucleotide is not acting by
      influencing the expression of G0S30, and may be targeting another gene. The
      phosphorothioated oligonucleotide was maximally inhibitory at a 50 nM
      concentration, which is near to the "physiological" concentration found with CpG
      containing oligonucleotides to activate mouse B lymphocytes. In the present work,
      increasing the concentration above 50 nM, or adding further quantities of control
      oligonucleotides, decreased the inhibition. It is suggested that by using low
      oligonucleotide concentrations (the "stealth" approach), one may avoid "tripping"
      an endogenous defense system directed against exogenous oligonucleotides, yet
      still get sufficient uptake to inhibit lymphocyte activation.

PMID- 8756336
TI  - Identification and characterization of BC1 RNP particles.
AB  - Rodent brain-specific small cytoplasmic BC1 RNA is an unusual RNA in several
      respects. It is an RNA polymerase III transcript expressed specifically in
      neurons, with regional and developmental regulation. Moreover, it is one of a few
      RNAs actively transported into dendrites. Three findings indicate that BC1 RNA
      exists as a ribonucleoprotein complex in vivo. First, the buoyant density of
      fractions containing BC1 RNA from brain extract on CsCI and Cs2SO4 gradients is
      1.45 g/ml and 1.55 g/ml, respectively; this is consistent with the density of RNA
      protein complexes. Second, in sucrose gradients, the BC1 particle has a larger S
      value (8.7S) than naked RNA (6.1S). Third, BC1 RNA from brain extracts migrates
      with retarded mobility compared to naked BC1 RNA during agarose gel
      electrophoresis. Additionally, in comparison to the signal recognition particle
      (SRP), the BC1 RNP is more heat resistant and less Mg(2+)-dependent. The buoyant
      density of the BC1 RNP suggests the presence of protein(s) with a total mass of
      about 138kD.

PMID- 8756338
TI  - Analysis of genetic heterogeneity, antigenicity, and biological characteristics
      of HIV-1 in a maternal transmitter and nontransmitter patient pair.
AB  - To obtain insight into the factors involved in vertical transmission, we compared
      the sequence diversity, seroreactivity, and biological characteristics of human
      immunodeficiency virus type 1 (HIV-1) derived from a transmitter and
      nontransmitter mother pair. Forty-two clones from the transmitter and 20 from the
      nontransmitter, spanning the principal neutralization determinant (PND) of the
      env gene, were sequenced and analyzed. The intrapatient sequence variation in
      transmitter and nontransmitter viruses was 12% and 36%, respectively, and the
      interpatient variation was 38%. In an effort to correlate immune responses to
      viral genetics, we analyzed the sera from these patients against a number of V3
      peptides from known HIV-1 isolates. We observed that (i) both the transmitter and
      nontransmitter sera demonstrated higher binding to V3 peptides based on SF-2 and
      MN sequences than to IIIB and Z6 isolates; (ii) the vertical transmission of HIV
      1 is correlated with the absence of high maternal antibody responses to the PND;
      and (iii) the high-affinity binding of the sera to SF-2 and MN V3 peptides
      correlated with the sequence analysis, indicating that the V3 sequences from both
      patients are more closely related to ADA, SF-162, and MN than to IIIB or Z6.
      Biological analysis of the viruses from these patients demonstrate that the
      transmitters' viruses infect a number of T-cell lines in vitro, whereas the
      nontransmitter viruses do not infect cell lines or the primary lymphocytes.

PMID- 8756339
TI  - Isolation and analysis of inducibility of the rat N-methylpurine-DNA glycosylase
      promoter.
AB  - Alkylations at base nitrogens in DNA are removed by excision repair, the first
      step of which is catalyzed by the repair enzyme N-methylpurine-DNA glycosylase
      (MPG). To study regulation of MPG expression, we have cloned the rat MPG
      promoter. A cosmid clone containing the rat MPG gene was isolated from a library
      using rat MPG cDNA as a probe. The 5' part of the MPG gene and the nontranscribed
      5'-flanking region were isolated and characterized. Transcription start sites of
      the rat MPG gene were identified by primer extension and S1 nuclease protection
      analysis of RNA from primary rat hepatocytes. Promoter activity of the 5'
      flanking noncoding region was shown by transfection in H4IIE rat hepatoma cells
      of various genomic MPG fragments cloned in front of the reporter gene
      chloramphenicol acetyltransferase. The rat MPG promoter does not contain a TATA
      box, but has a CCAAT sequence element and putative binding sites for the
      transcription factors Sp1, AP-2, AP-3, Ets-1, PEA3, NF-1, p53, c-Myc, NF-kappa B,
      and the glucocorticoid receptor. The activity of the rat MPG promoter was found
      to be inducible by the tumor promoter TPA and UV light, but not to a significant
      extent by methylating agents and ionizing radiation.

PMID- 8756340
TI  - Fidelity and predominant mutations produced by deep vent wild-type and
      exonuclease-deficient DNA polymerases during in vitro DNA amplification.
AB  - Denaturing gradient gel electrophoresis (DGGE) was used to examine error rates
      and mutations induced by native (wt) and exonuclease-deficient (exo-) Deep Vent
      DNA polymerases during DNA amplification by polymerase chain reaction (PCR), in
      the presence or absence of the T4 bacteriophage gene 32 protein (gp32).gp32 was
      found to decrease the error rate of the wt, but not that of the exo-, Deep Vent.
      The average errors per base duplication for the native form were 8.0 x 10(-5) and
      6.0 x 10(-5) in the absence and presence of gp32, respectively. For the exo-
      form, the error rates were 2.0 x 10(-4) and 2.2 x 10(-4) errors per base
      duplication in the absence and presence of gp32, respectively. Examination of
      mutations produced by native Deep Vent showed that A/T to G/C transition
      predominated, consistent with the results of our earlier studies with DNA
      polymerases derived from other thermophilic bacteria. These results indicate that
      PCR with high fidelity can be achieved by using wt Deep Vent in combination with
      gp32.

PMID- 8756341
TI  - The genomic structure of the murine alpha 4 integrin gene.
AB  - The VLA-4 (alpha 4 beta 1) integrin is a leukocyte glycoprotein involved in both
      cell-extracellular matrix and cell-cell interactions. We report here the cloning
      of the murine alpha 4 gene whose protein product is antigenically related to the
      human VLA-4 alpha chain. The alpha 4 m gene is about 75 kb long and consists of
      28 exons, ranging in size from 46 bp (exon 13) to 437 bp (exon 1). The introns
      varied from 79 bp (intron 8) to more than 17 kb (intron 2). Three mRNA
      transcripts from this alpha 4 m gene can be visualized on Northern blot. After
      cloning the 3' untranslated region (3' UTR), four polyadenylation sites could be
      identified, presumably responsible for the presence of three to four transcripts
      of the alpha 4 gene, differing substantially in length.

PMID- 8756342
TI  - Isolation and characterization of a vitellogenin cDNA from rainbow trout
      (Oncorhynchus mykiss) and the complete sequence of a phosvitin coding segment.
AB  - Phosvitins are extensively phosphorylated serine-rich proteins that are derived
      from a large hepatic phosphoglycolipoprotein, vitellogenin, and are deposited,
      after suitable processing, in the eggs of oviparous vertebrates. Despite their
      widespread occurrence and apparent importance for early embryonic development,
      very few phosvitins have been sequenced thus far, including no teleost protein.
      We used a polymerase chain reaction (PCR)-assisted approach to isolate a
      vitellogenin cDNA clone, complementary to mRNA synthesized in the liver of
      estrogen-treated rainbow trout. This clone contains a sequence that corresponds
      to the composition of a phosvitin previously characterized in our laboratory. The
      amino terminus was identified by amino acid sequencing of the protein. The
      carboxyl terminus was inferred from homology with other phosvitin-specific
      sequences from chicken, Xenopus, and lamprey. Trout phosvitin appears to be a
      small, 53-residue-long protein displaying the long runs of serines that are
      characteristic of all phosvitins described so far.

PMID- 8756343
TI  - Knockouts of Src-family kinases: stiff bones, wimpy T cells, and bad memories.

PMID- 8756344
TI  - The EVES motif mediates both intermolecular and intramolecular regulation of c
      Myb.
AB  - The c-Myb transcription factor is a proto-oncoprotein whose latent transforming
      activity can be unmasked by truncation of either terminus. Because both ends of
      Myb are involved in negative regulation, we tested whether they could associate
      in a two-hybrid assay and identified a carboxy-terminal motif that interacts with
      the amino-terminal DNA-binding domain. The EVES motif is highly conserved in
      vertebrate c-Myb proteins and contains a known site of phosphorylation previously
      implicated in the negative regulation of c-Myb. Interestingly, a related EVES
      motif is present in p100, a ubiquitously expressed transcriptional coactivator
      found in diverse species. We show that p100 interacts with and influences the
      activity of c-Myb, implicating it in the regulation of c-Myb, differentiation,
      and cell growth. Our results suggest that Myb is regulated by a novel mechanism
      in which intramolecular interactions and conformational changes control the
      intermolecular associations among Myb, p100, and the transcriptional apparatus.

PMID- 8756345
TI  - Early loss of the retinoblastoma gene is associated with impaired growth
      inhibitory innervation during melanotroph carcinogenesis in Rb+/- mice.
AB  - To better understand the cell lineage-specific character of retinoblastoma (Rb)
      gene inactivation during tumor formation, the earliest stages of spontaneous
      melanotroph carcinogenesis in Rb+/- heterozygous mice have been subjected to
      sequential analyses. The first atypical cells are detected in the pituitary
      intermediate lobe during a period corresponding to the cessation of melanotroph
      proliferation between 35 and 60 days after birth. Atypical cells contain no wild
      type copy of the Rb gene and synchronously form early atypical proliferates (EAP)
      in the subsequent 30-60 day period. In contrast to surrounding mature
      melanotrophs with the wild-type Rb gene, Rb-negative cells in EAP continue to
      proliferate well past postnatal day 60, and fail to be innervated by growth
      inhibitory dopaminergic nerve terminals. Atypical melanotrophs remain competent
      for dopamine D2 receptor stimulation and undergo S-phase apoptosis in close
      proximity to nerve terminals. These results indicate a key role for the Rb
      protein in the onset of neuron-neuroendocrine cell interactions. This role may
      explain cell-type-specific neuroendocrine carcinogenesis associated with
      inactivation of the ubiquitously expressed Rb gene.

PMID- 8756346
TI  - A novel mesoderm inducer, Madr2, functions in the activin signal transduction
      pathway.
AB  - A functional assay to clone mouse mesoderm inducers has identified the mouse gene
      Mad related 2 (Madr2). Madr2 induces dorsal mesoderm from Xenopus ectoderm and
      can mimic the organizer in recruiting neighboring cells into a second axis. By
      analyzing the expression of a lacZ/Madr2 fusion protein, we find Madr2 confined
      to the nucleus in the deep, anterior cells of the second axis, whereas in
      epidermal and more posterior cells the protein is cytoplasmically localized. This
      context-dependent nuclear localization suggests that in certain regions of the
      embryo, Madr2 responds to a localized signal and amplifies this signal to form
      the second axis. Furthermore, although Madr2 remains unlocalized in ectodermal
      explants, addition of activin enhances the concentration of Madr2 in the nucleus.
      Significantly, a functional lacZ fusion to a carboxy-terminal portion of Madr2 is
      nuclear localized even in the absence of activin. This indicates that Madr2
      contains a domain that can activate downstream components and a repressive domain
      that anchors the protein in the cytoplasm. Nuclear localization of Madr2 in
      response to activin, and the activin-like phenotypes induced by overexpression of
      Madr2, indicate that Madr2 is a signal transduction component that mediates the
      activity of activin.

PMID- 8756347
TI  - In vitro selection of preferred DNA pairing sequences by the Escherichia coli
      RecA protein.
AB  - The RecA protein and other DNA strand exchange proteins are characterized by
      their ability to bind and pair DNA in a sequence-independent manner. In vitro
      selection experiments demonstrate, unexpectedly, that RecA protein has a
      preferential affinity for DNA sequences rich in GT composition. Such GT-rich
      sequences are present in loci that display increased recombinational activity in
      both eukaryotes and prokaryotes, including the Escherichia coli recombination
      hotspot, chi (5'-GCTGGTGG-3'). Interestingly, these selected sequences, or chi
      containing substrates, display both an enhanced rate and extent of homologous
      pairing in RecA protein-dependent homologous pairing reactions. Thus, the binding
      and pairing of DNA by RecA protein is composition-dependent, suggesting that a
      component of the elevated recombinational activity of chi and increased genomic
      rearrangements at certain DNA sequences in eukaryotes is contributed by enhanced
      DNA pairing activity.

PMID- 8756348
TI  - Nutrients, via the Tor proteins, stimulate the association of Tap42 with type 2A
      phosphatases.
AB  - We identified an essential Saccharomyces cerevisiae protein, Tap42, that
      associates with Sit4, a type 2A-related protein phosphatase, and with the type 2A
      phosphatase catalytic subunits. The association of Tap42 with the phosphatases
      does not require the previously identified phosphatase subunits. Genetic analysis
      suggests that Tap42 functions positively with both phosphatases. Mutations in
      TAP42 can confer almost complete rapamycin resistance. In addition, Tap42/Sit4
      and Tap42/PP2A complex formation is regulated by nutrient growth signals and the
      rapamycin-sensitive Tor signaling pathway. These findings, combined with the
      defect in translation of the tap42-11 mutant at the nonpermissive temperature,
      suggest that Tap42, Sit4, and PP2A are components of the Tor signaling pathway.

PMID- 8756349
TI  - A widespread transposable element masks expression of a yeast copper transport
      gene.
AB  - The trace element copper (Cu) is essential for cell growth. In this report we
      describe the identification of a new component of the high-affinity Cu transport
      machinery in yeast, encoded by the CTR3 gene. Ctr3p is a small intracellular
      cysteine-rich integral membrane protein that restores high-affinity Cu uptake,
      Cu, Zn superoxide dismutase activity, ferrous iron transport, and respiratory
      proficiency to strains lacking the CTR1 (Cu transporter 1) gene. In most commonly
      used Saccharomyces cerevisiae laboratory strains, expression of CTR3 is abolished
      by a Ty2 transposon insertion that separates the CTR3 promoter from the
      transcriptional start sites by 6 kb. In strains that do not possess a Ty2
      transposon at the CTR3 locus, expression of CTR3 is repressed by copper and
      activated by copper starvation. In such strains inactivation of both CTR1 and
      CTR3 is required to generate lethal copper-deficient phenotypes. Although Ctr1p
      and Ctr3p can function independently in copper transport, the expression of both
      proteins provides maximal copper uptake and growth rate under copper-limiting
      conditions. These results underscore the importance of mobile DNA elements in the
      alteration of gene function and phenotypic variation.

PMID- 8756350
TI  - Frequent provirus insertional mutagenesis of Notch1 in thymomas of MMTVD/myc
      transgenic mice suggests a collaboration of c-myc and Notch1 for oncogenesis.
AB  - The MMTVD/myc transgenic mice spontaneously develop oligoclonal CD4+CD8+ T-cell
      tumors. We used provirus insertional mutagenesis in these mice to identify
      putative collaborators of c-myc. We found that Notch1 was mutated in a high
      proportion (52%) of these tumors. Proviruses were inserted upstream of the exon
      coding for the transmembrane domain and in both transcriptional orientations.
      These mutations led to high expression of truncated Notch1 RNAs and proteins (86
      110 kD). In addition, many Notch1-rearranged tumors showed elevated levels of
      full-length Notch1 transcripts, whereas nearly all showed increased levels of
      full-length (330-kD) or close to full-length (280-kD) Notch1 proteins. The 5' end
      of the truncated RNAs were determined for some tumors by use of RT-PCR and 5'
      RACE techniques. Depending on the orientation of the proviruses, viral LTR or
      cryptic promoters appeared to be utilized, and coding potential began in most
      cases in the transmembrane domain. Pulse-chase experiments revealed that the 330
      kD Notch1 proteins were processed into 110- and 280-kD cleavage products. These
      results suggest that Notch1 can be a frequent collaborator of c-myc for
      oncogenesis. Furthermore, our data indicate that Notch1 alleles mutated by
      provirus insertion can lead to increased expression of truncated and full-length
      (330/280-kD) Notch1 proteins, both being produced in a cleaved and uncleaved
      form.

PMID- 8756351
TI  - Genetic determinants of p53-induced apoptosis and growth arrest.
AB  - Previous studies have suggested that expression of p53 in cancer cells can result
      in either growth arrest or apoptosis. Accordingly, expression of p53 in a series
      of colorectal cancer cell lines yielded growth arrest in some lines (A-lines) and
      apoptosis in others (D-lines). To investigate the basis of this difference, we
      evaluated the role of p21WAF1/Cip1, a known mediator of p53-induced growth
      arrest. Inactivation of p21 by homologous recombination converted an A-line to a
      D-line, suggesting that p21 could protect cells from apoptosis. However,
      examination of p53-induced p21 expression in naturally occurring D-lines and A
      lines demonstrated that the induction of p21 could not account for the
      differential response to p53. Moreover, when a D-line was fused to an A-line, the
      resulting hybrid cells underwent apoptosis in response to p53, indicating that
      the apoptosis pathway was dominant over the growth arrest pathway. Therefore, the
      apoptotic response to p53 in colorectal cancer cells is modulated by at least two
      factors: p21-mediated growth arrest that can protect cells from apoptosis in A
      cells, and trans-acting factors in D-cells that can overcome this protection,
      resulting in cell death.

PMID- 8756352
TI  - The Caenorhabditis elegans gene sem-4 controls neuronal and mesodermal cell
      development and encodes a zinc finger protein.
AB  - Neuronal and mesodermal cell types are generated in separate cell lineages during
      the larval development of Caenorhabditis elegans. Here we demonstrate that the
      gene sem-4 is required in both types of lineages for the normal development of
      neuronal and mesodermal cell types. The sem-4 gene encodes a protein containing
      seven zinc finger motifs of the C2H2 class, four of which are arranged in two
      pairs widely separated in the primary sequence of the protein. These pairs of
      zinc fingers are similar to pairs of zinc fingers in the protein encoded by the
      Drosophila homeotic gene spalt and in the human transcription factor PRDII-BF1.
      Analysis of sem-4 alleles suggests that different zinc fingers in the SEM-4
      protein may function differentially in neuronal and mesodermal cell types. We
      propose that sem-4 interacts with different transcription factors in different
      cell types to control the transcription of genes that function in the processes
      of neuronal and mesodermal cell development.

PMID- 8756354
TI  - Catalytic asymmetric aminohydroxylation provides a short taxol side-chain
      synthesis.
AB  - The p-toluenesulfonamide derivate of the C-13 side-chain of taxol was prepared on
      a one third mole scale in a single step from methyl cinnamate. The process
      employed is catalytic asymmetric aminohydroxylation (catalytic AA). In the
      present case, there is no work-up other than filtration of the pure product which
      is insoluble in the reaction mixture. The sulfonamide protecting group is removed
      by acidic hydrolysis.

PMID- 8756353
TI  - Zygotic degradation of two maternal Cdc25 mRNAs terminates Drosophila's early
      cell cycle program.
AB  - In Drosophila embryos the maternal/zygotic transition (MZT) in cell cycle control
      normally follows mitosis 13. Here we show that this transition requires
      degradation of two maternal mRNAs, string and twine, which encode Cdc25
      phosphatases. Although twine is essential for meiosis and string is essential for
      most mitotic cycles, the two genes have mutually complementing, overlapping
      functions in the female germ line and the early embryo. Deletion of both gene
      products from the female germ line arrests germ-line development. Reducing the
      maternal dose of both products can lower the number of early embryonic mitoses to
      12, whereas increasing maternal Cdc25(twine) can increase the number of early
      mitoses to 14. Blocking the activation of zygotic transcription stabilizes
      maternal string and twine mRNAs and also allows an extra maternal mitosis, which
      is Cdc25 dependent. We propose that Drosophila's MZT comprises a chain reaction
      in which (1) proliferating nuclei deplete factors (probably mitotic cyclins)
      required for cell cycle progression; (2) this depletion causes the elongation of
      interphases and allows zygotic transcription; (3) new gene products accumulate
      that promote degradation of maternal mRNAs, including string and twine; and (4)
      consequent loss of Cdc25 phosphatase activity allows inhibitory phosphorylation
      of Cdc2 by Dwee1 kinase, effecting G2 arrest. Unlike timing or counting
      mechanisms, this mechanism can compensate for losses or additions of nuclei by
      altering the timing and number of the maternal cycles and thus will always
      generate the correct cell density at the MZT.

PMID- 8756355
TI  - Using the process of reactive immunization to induce catalytic antibodies with
      complex mechanisms: aldolases.
AB  - The process of reactive immunization has been used to induce efficient aldolase
      catalytic antibodies that use the enamine mechanism of natural enzymes. Reactive
      immunogens are those that react chemically during induction of the immune
      response. This same reaction is used later in catalysis. In essence one immunizes
      with the equivalent of a mechanism-based inhibitor. The difference is that
      instead of inhibiting a mechanism, a mechanism is induced. This advance allows
      the experimenter to dictate the exact mechanism by which catalytic antibodies
      proceed. The hapten used in the present study is a 1,3-diketone that both traps
      the requisite lysine residue to initiate formation of the enamine and induces a
      binding pocket that overcomes the entropic barrier of this bimolecular reaction.

PMID- 8756356
TI  - Asymmetric organic synthesis with catalytic antibodies.
AB  - The science of catalytic antibodies has undergone a rapid maturation process
      within its first nine years of existence. From initial 'proof of concept' and
      demonstration of fundamental, enzyme-like characteristics, antibodies have been
      shown to catalyze a remarkably broad scope of organic transformations, including
      difficult and unfavorable chemical reactions. Yet, the ultimate testing ground
      for new concepts in organic chemistry has always been the synthesis of natural
      products. Here we focus on several issues related to the applicability of
      antibody catalysis in organic synthesis. We show that (a) in the hydrophobic
      environment of the antibody active site, short-lived intermediates can be formed
      and reacted in a controlled way, thus allowing antibodies to catalyze reactions
      that are normally incompatible with aqueous media, (b) the intrinsic order of
      reactivity (chemoselectivity) in a series of structurally related enol ethers and
      ketals can be inverted from 1:10 in the uncatalyzed hydrolysis reaction to 1000:1
      under antibody catalysis, and (c) an efficient total synthesis of alpha
      multistriatin, an important, biologically active natural product can be achieved
      via antibody catalysis.

PMID- 8756357
TI  - Expression of de novo designed alpha-helical bundles.
AB  - The successful design of proteins requires careful consideration of the
      multiplicity of forces that stabilize their three-dimensional structures
      including hydrophobic interactions, hydrogen-bonding, electrostatics and weakly
      polar interactions. Early attempts to design proteins relied too heavily on
      hydrophobic interactions to provide stability, resulting in structures with
      dynamic properties. Addition of more specific interactions to these initial
      designs gives rise to proteins with more native-like properties. This manuscript
      describes the design of native-like three- and four-helix bundles, and their
      cloning and expression of these proteins.

PMID- 8756358
TI  - Molecular recognition and assembly.
AB  - The synthesis and characterization of a series of self-assembling capsules is
      described. Assembly takes place as a result of the self-complementary hydrogen
      bonding patterns on the subunit pieces and dimerization occurs in such a manner
      that the concave surfaces of the two subunits are directed at one another. This
      feature gives rise to close-shelled capsules which are shown to encapsulate
      smaller guest species. Selectivity is shown for guests ranging in size from
      methane to adamantane derivatives. Shape selectivity is shown in special capsules
      capable of recognizing disc-like molecules such as benzene and cyclohexane.
      Disproportionation reactions are shown to exist between capsules of slightly
      different sizes, and these are shown to be controlled by the nature of the guest
      species. The use of these capsules as reaction chambers is proposed.

PMID- 8756359
TI  - Epstein-Barr virus-associated undifferentiated carcinoma with lymphoid stroma of
      the salivary gland in Japanese patients. Comparison with benign lymphoepithelial
      lesion.
AB  - BACKGROUND: Undifferentiated carcinoma with lymphoid stroma (UCLS) arising in the
      salivary gland is a rare tumor, except for its geographic concentration among
      Eskimo and southern Chinese populations. Five cases of salivary gland UCLS in
      Japanese patients are presented here and compared with benign lymphoepithelial
      lesions (BLELs) with regard to their association with Epstein-Barr virus (EBV),
      p53 expression, and cell proliferative activity. METHODS: Formalin fixed,
      paraffin embedded sections of 5 cases of UCLS selected from 1676 patients with
      primary tumors of the major salivary gland and 7 cases of BLEL were examined
      using in situ hybridization for EBV-encoded RNAs (EBERs), along with
      immunostaining for p53 and Ki-67 (MIB-1). RESULTS: The incidence of UCLS was 0.3%
      among patients with major salivary gland tumors. EBER hybridization signals were
      strongly expressed in most of the neoplastic cells in all five cases of UCLS,
      whereas there was no signal in BLEL and surrounding nontumorous salivary gland
      tissues. All cases of UCLS showed strongly positive immunostaining for p53 in the
      tumor cell nuclei. By contrast, only one case of BLEL was positively stained for
      p53 in dysplastic epimyoepithelial cells, which showed focal immunostaining. Cell
      proliferative activity assessed using the Ki-67 labeling index was significantly
      higher in tumor cells of UCLS than in epimyoepithelial cells of BLEL.
      CONCLUSIONS: UCLS of the salivary gland is an extremely rare tumor in Japanese
      patients characterized by consistent association with EBV. Distinction between
      BLEL and UCLS is possible by examining for evidence of EBV infection, expression
      of p53, and cell proliferative activity.

PMID- 8756360
TI  - Detection of human papillomavirus in esophageal squamous cell carcinoma.
AB  - BACKGROUND: Human papillomavirus (HPV) DNA has been identified in esophageal
      carcinomas. However, the incidence of HPV varies significantly in different
      geographic locations. In the current study, neoplasms from two separate
      geographic regions were analyzed for the presence of HPV DNA: METHODS: One
      hundred and ten esophageal squamous cell carcinomas, 83 from Beijing, China and
      27 from Cincinnati, Ohio, were examined for the presence of HPV DNA: In situ
      hybridization and polymerase chain reaction (PCR) using both consensus primers
      for the HPV L1 gene and type specific primers for the E6 gene of HPV types 6, 16,
      and 18 were performed. RESULTS: In situ hybridization failed to demonstrate any
      HPV type (6, 11, 16, 18, 31, 33, or 35) in any tumor specimen. Likewise, PCR
      using consensus primers for the HPV L1 gene was negative in all samples. Three of
      the Chinese specimens (4.29%) were positive for HPV using E6 type specific
      primers. One tumor contained HPV type 6 DNA, whereas the other 2 contained HPV
      type 16 DNA. One Cincinnati tumor (4.35%) was positive for HPV 16 by type
      specific primer. None of the specimens contained HPV 18 DNA. CONCLUSIONS: The
      incidence of HPV DNA in esophageal carcinoma specimens from Beijing, China and
      Cincinnati, Ohio is similar. The incidence of HPV in tumors from Beijing is
      significantly lower than that reported for those from other regions of China
      where the incidence of esophageal cancer is higher. Thus, although HPV may play a
      role in esophageal carcinogenesis, this role may be more pronounced in those
      regions of the world with a high incidence of the disease, and may be less
      important in areas with moderate or low risks for esophageal cancer.

PMID- 8756361
TI  - Brain metastases from colorectal carcinoma. The long term survivors.
AB  - BACKGROUND: Brain metastases occur in 25% to 35% of all cancer patients, with
      colorectal carcinoma accounting for approximately 8% of these. Information about
      patients with brain metastases from colorectal carcinoma is limited, with the
      largest previous series reporting only 40 patients. To date there have been no
      reports describing the subgroup of patients with long term survival ( > 1 yr).
      METHODS: A retrospective review of 150 patients seen at the Mayo Clinic between
      1976 and 1993 with pathologic (56) and/or radiographic (94) confirmation of brain
      metastases from colorectal carcinoma is presented. RESULTS: The majority of
      patients (82%) with brain metastases from colorectal carcinoma have concomitant
      extracerebral metastases, especially in the lungs. Only 16% of the patients
      survived > 1 year after diagnosis (4 > 4 yrs., 2 > 10 yrs). Of these, 92% had
      single cerebral metastases and 38% had no systemic metastases. In addition, young
      age and the absence of bony metastases or memory loss were associated with
      increased survival. Median survival for all of the patients receiving surgery and
      radiotherapy (39), surgery alone (11), radiotherapy alone (79) and supportive
      care (17) are 42, 45, 16, and 8 weeks, respectively. Thirty percent of the
      patients treated with radiotherapy showed regression of their tumors on follow-up
      head scans; three had complete regression. CONCLUSIONS: One-year survivors of
      brain metastases from colorectal carcinoma were uncommon, accounting for 16% of
      the patients and most of these (92%) had solitary lesions. Nineteen of 24 long
      term survivors had surgical resection as part of their treatment. Given the
      similar results in patients treated with surgery plus radiotherapy and those
      treated with surgery alone, as well as the potential long term side effects of
      radiotherapy, withholding radiotherapy for those patients with the possibility of
      long term survival should be considered.

PMID- 8756362
TI  - Prognostic significance of tumor fixation of rectal carcinoma. Implications for
      adjunctive radiation therapy.
AB  - BACKGROUND: This study was conducted to assess the prognostic significance of
      adjunctive radiation in the surgical management of rectal carcinoma patients with
      tumor fixation. METHODS: Two hundred and ninety-seven patients with a histologic
      diagnosis of adenocarcinoma of the rectum were treated with high dose
      preoperative radiation ( > or = 45 Gray [Gy]) followed by surgical resection of
      the tumor (Group A). One hundred and seventy-four patients underwent initial
      curative surgery (Group B) followed by selective postoperative radiation (45-50
      Gy) for those with pathologic T3, T4, or N+ (B2, C) cancers (N = 143). The two
      patient groups were compared by presenting clinical stage of the disease to
      assess the prognostic significance of tumor fixation on results of adjunctive
      therapy. Follow-up ranged from 24 months to 180 months. RESULTS: The 5-year
      actuarial survival of Groups A and B was similar, 69% and 61% respectively.
      Survival was significantly better for Group A patients with fixed cancer (57% vs.
      33%, P = 0.003). Survival was also better for patients in Group A with tumors
      located in the distal rectum (70% vs. 56%, P = 0.02). The local recurrence rate
      for patients with tumors located in the distal rectum was 17% for Group A and 19%
      for Group B (P = 0.74). The local recurrence rate for fixed cancers was 23% and
      50% for Group A and Group B respectively (P = 0.0009). The incidence of small
      bowel complications (Grade 3 or 4) was lower for patients undergoing preoperative
      radiation compared with patients treated with postoperative radiation, (4% vs.
      13%, P < 0.05). CONCLUSIONS: When special considerations of sphincter-preserving
      surgery are not an issue, mobile rectal carcinoma may be effectively treated with
      surgery and selective postoperative radiation. However, fixed tumors, especially
      those located in the distal rectum, are better treated with high dose
      preoperative radiation.

PMID- 8756363
TI  - The effect of calcium and vitamin supplements on the incidence and recurrence of
      colorectal adenomatous polyps.
AB  - BACKGROUND: Recent attention has focused on calcium and certain vitamins as
      potential protective agents against colorectal neoplasia. METHODS: Two case
      control studies were conducted on patients who underwent colonoscopy between 1986
      and 1988, comparing 297 patients with newly diagnosed adenomas with 505 controls
      (without current or prior history of neoplasia), and 198 patients with recurrent
      adenomas with 347 recurrent controls (with no current neoplasia, but with a
      history of polypectomy). Subjects were interviewed regarding their regular usage
      of supplementation with vitamins A, C, D, and E, or with calcium, multivitamins,
      or any vitamin supplements. RESULTS: No consistent associations were observed
      with the use of any of these supplements. CONCLUSIONS: More studies are necessary
      to confirm these findings. It may be necessary to develop other chemopreventive
      agents, such as aspirin, for colorectal neoplasia.

PMID- 8756364
TI  - Comparison of DNA topoisomerase II alpha expression in small cell and nonsmall
      cell carcinoma of the lung. In search of a mechanism of chemotherapeutic
      response.
AB  - BACKGROUND: Small cell carcinoma of the lung (SCLC) is distinguished from
      nonsmall cell carcinoma (NSCLC) by its exquisite initial sensitivity to
      chemotherapy. Antineoplastic drugs effective against SCLC include doxorubicin,
      etoposide, and others. Recently, the molecular target of these drugs has been
      identified as the alpha form of DNA topoisomerase II, which is important in DNA
      replication and in the separation of chromosomes during normal cellular division.
      In this study we compared DNA topoisomerase II alpha expression in SCLC and NSCLC
      by immunohistochemistry. We hypothesized that the sensitivity of SCLC and
      relative insensitivity of NSCLC to these chemotherapeutic agents stem from
      different frequencies of DNA topoisomerase II alpha expression. METHODS: DNA
      topoisomerase II alpha expression was analyzed in 17 cases of SCLC and 24 cases
      of NSCLC by immunohistochemistry utilizing a monoclonal antibody recognizing the
      alpha isoform of DNA topoisomerase II. A topo II index was determined by dividing
      the number of tumor nuclei expressing DNA topoisomerase II by the total number of
      tumor nuclei counted. RESULTS: A significantly higher frequency of DNA
      topoisomerase II alpha expression was identified in SCLC (P < 0.001). The average
      topo II index for SCLC was 0.60 (range: 0.45-0.76) compared with NSCLC, 0.31
      (range: 0.05-0.75). CONCLUSIONS: We conclude that DNA topoisomerase II alpha is
      expressed at a higher frequency in SCLC than in NSCLC, and that this expression
      is possibly involved in the response of SCLC to chemotherapeutic agents.

PMID- 8756365
TI  - Diagnostic value of CA 72-4, carcinoembryonic antigen, CA 15-3, and CA 19-9 assay
      in pleural fluid. A study of 207 patients.
AB  - BACKGROUND: The differential diagnosis of pleural effusion is a frequent clinical
      problem. Several tumor markers have been evaluated in pleural fluid, but the
      value of CA 72-4 assay and of combinations of tumor marker assays has not been
      firmly established. To find a minimally invasive tool for differentiating between
      pleural effusions of malignant or benign origin, the authors assessed the
      diagnostic value of CA 72-4, carcinoembryonic antigen (CEA), CA 15-3, and CA 19-9
      assays in pleural fluid individually and in combination. METHODS: The authors
      prospectively studied 207 patients with pleural effusion (65 malignant, 48
      tuberculous, 24 parapneumonic, 26 transudates, 14 miscellaneous, and 30 of
      unknown nonneoplastic origin). The levels of CA 72-4, CEA, CA 15-3, and CA 19-9
      were measured in pleural fluid by radioimmunoassay. RESULTS: CA 72-4 assay in
      pleural fluid had an acceptable sensitivity and very good specificity for
      diagnosing malignant pleural effusion. The combination of CA 72-4 plus CEA plus
      CA 15-3 yielded the best accuracy, 0.90 (95% confidence interval [CI] 0.85-0.94),
      with a sensitivity of 0.78 (95% CI, 0.67-0.88), specificity of 0.95 (95% CI, 0.90
      0.98), positive predictive value of 0.88 (95% CI, 0.77-0.95), and negative
      predictive value of 0.91 (range, 0.85-0.94). A good clinical strategy may be to
      begin with a CEA assay (specificity of I) and then, if it is negative, to add CA
      15-3 or even CA 72-4 assays to improve sensitivity. The diagnosis of mesothelioma
      is more likely with a high CA 15-3 level and normal CEA and CA 19-9 levels.
      CONCLUSIONS: Assays of CEA, CA 72-4, and CA 15-3 in pleural fluid, or the
      combination of CEA with CA 15-3 and CA 72-4, was useful in differentiating
      between pleural effusion of malignant and benign origin.

PMID- 8756366
TI  - Phase II study of paclitaxel in patients with previously treated osteosarcoma and
      its variants.
AB  - BACKGROUND: Patients with osteosarcoma and its variants who did not respond to
      standard chemotherapy including doxorubicin, ifosfamide, cisplatin, and high dose
      methotrexate were treated with paclitaxel so that its therapeutic activity in
      these patients could be determined. METHODS: We conducted a Phase II study of
      paclitaxel in patients with conventional osteosarcoma (10), malignant fibrous
      histiocytoma of the bone (3) and dedifferentiated chondrosarcoma (2) whose
      disease had progressed after prior standard chemotherapy including doxorubicin,
      cisplatin, ifosfamide, and high dose methotrexate. Paclitaxel was administered at
      a starting dose of 175 mg/m2 as a 24-hour infusion with standard premedication
      every 21 days or upon hematologic recovery (absolute granulocyte count [AGC] >
      1500/microliters, platelets > 100,000/microliters). Neupogen was not used
      routinely. The study was conducted based on a two-stage design. A total of 17
      patients were entered into the protocol. Two were ineligible since they had
      Ewing's sarcoma. Responses were assessed radiographically and pathologically when
      feasible, using standard criteria. RESULTS: Fifteen eligible patients were
      treated in the first stage of the study. Median age of the patients was 31 years
      (range, 19-61 yrs). There were 8 females and 7 males with a Zubrod performance
      status of 0 or 1. One patient achieved a mixed response and 14 developed
      progressive disease. Median AGC nadir was 0.3, on Day 13, lasting 5 days. Median
      platelet nadir was 134, on Day 8. There were no Grade III or IV nonhematologic
      toxicities and no deaths related to treatment. CONCLUSIONS: Paclitaxel, at this
      dose and schedule, is well tolerated but inactive in this patient population.

PMID- 8756367
TI  - Chondrosarcoma of the pelvis. Prognostic factors for 67 patients treated with
      definitive surgery.
AB  - BACKGROUND: Chondrosarcoma (CS) most commonly involves the pelvis. Local and
      systemic failures often result in poor outcome. Prognostic factors that determine
      patient outcome remain ill-defined. METHODS: We retrospectively analyzed 67
      patients with CS of the pelvis treated by definitive surgery from January 1970 to
      December 1992. All patients had localized disease including Grade 1 (19
      patients), Grade 2 (18 patients), Grade 3 (17 patients), and dedifferentiated (13
      patients) tumors. Thirty-two patients underwent a limb-sparing surgical resection
      and 35 patients underwent hemipelvectomy. Follow-up was available for all
      patients. The median duration of follow-up for the survivors was 115 months
      (range, 24-288 months). RESULTS: At last follow-up, 52% of the patients were
      disease free, 8% were alive with disease, 36% died of disease, and 4% died of
      other causes. Nineteen patients (28%) had developed a local recurrence (LR). The
      median time to LR was 23 months (range, 1-111 months). Independent variables in a
      multivariate analysis associated with increased risk of LR included inadequate
      surgical margin, tumor epicenter in the pubis, and high grade histology. LR did
      not influence overall patient survival. Twenty-three patients (36%) developed
      distant metastases at a median time of 9 months (range, 1-111 months)
      postoperatively. Metastases developed in 0% of the patients with Grade 1, 20% of
      the patients with Grade 2 60% of the patients with Grade 3 and 75% of patients
      with dedifferentiated CS. On multivariate analysis, histologic high grade was the
      only significant predictive variable for distant relapse (P = 0.005).
      CONCLUSIONS: The critical issue for a favorable outcome in low grade CS of the
      pelvis is adequate surgical excision (i.e., negative surgical margin). The high
      rate of systemic failure in high grade and dedifferentiated CS, despite adequate
      surgery, emphasizes the need for more effective systemic therapy.

PMID- 8756368
TI  - Porocarcinoma of the heel. A case report with unusual histologic features.
AB  - BACKGROUND: Eccrine porocarcinoma is an uncommon neoplasm of the intraepidermal
      sweat gland duct. METHODS: A case of porocarcinoma of the right heel in a male
      age 51 years is described with a review of pertinent literature. The surgically
      excised neoplasm was evaluated by routine histology and transmission electron
      microscopy. RESULTS: The porocarcinoma showed extensive nuclear pleomorphisms
      with frequent, multinucleated tumor giant cells, focal epidermotrophic spread
      within the epidermis, a peripheral, eccrine syringofibroadenoma-like growth
      pattern, and an origin in a contiguous eccrine poroma. Ultrastructurally, the
      squamous tumor cells contained rare intracytoplasmic lumens. CONCLUSIONS: The
      extensive nuclear pleomorphism with frequent tumor giant cells was an unusual
      feature of the porocarcinoma. Its epidermotrophic spread within the epidermis and
      its origin in a contiguous eccrine poroma supported the diagnosis of
      porocarcinoma. The eccrine syringofibroadenoma-like growth pattern in the
      periphery of the tumor was a unique and previously undescribed feature of the
      porocarcinoma. The presence of intracytoplasmic lumens in squamous tumor cells
      mimicked embryonic development of the intraepidermal sweat gland duct.

PMID- 8756369
TI  - Malignant melanoma: relationship of the human leukocyte antigen class II gene
      DQB1*0301 to disease recurrence in American Joint Committee on Cancer Stage I or
      II.
AB  - BACKGROUND: Melanoma patients who carry the human leukocyte antigen (HLA) Class
      II allele DQB1*0301 have an increased frequency of metastases at presentation
      compared with those lacking HLA-DQB1*0301. This study was designed to determine
      whether HLA-DQB1*0301 is associated with an increased risk of recurrence in
      melanoma patients presenting with American Joint Committee on Cancer (AJCC) Stage
      I or II (localized) disease. METHODS: Molecular oligotyping of HLA-DQ genes was
      performed for 259 patients with AJCC Stage I or II melanoma. Rate of disease
      recurrence was determined by retrospective review and prospective follow-up.
      Kaplan-Meier analysis, log rank, and proportional hazard (Cox) comparison were
      performed. RESULTS: Median follow-up was 24 months. Minimum follow-up was 6
      months. Although HLA-DQB1*0301-positive and -negative patients were balanced with
      regard to standard melanoma prognostic factors (primary tumor thickness, level of
      invasion, presence of ulceration, anatomic location, and sex), HLA-DQB1*0301
      positive patients were more likely to develop locally recurrent, regional, or
      distant metastatic melanoma during follow-up (actuarial median disease free
      survival 48 months [DQB1*0301-positive patients] vs. 97 months [DQB1*0301
      negative patients]; log rank P = 0.0002). HLA-DQB1*0301 status, in addition to
      primary tumor thickness, was an independent prognostic indicator in these
      patients (Cox multivariate P = 0.02). CONCLUSIONS: Patients presenting with
      localized melanoma who carry HLA-DQB1*0301 are at an increased risk of developing
      recurrent disease compared with stage-matched patients who lack this allele. HLA
      DQB1*0301 is a genomic marker which independently identifies melanoma patients in
      whom recurrence is more likely, and is potentially useful in selecting those most
      likely to benefit from adjuvant therapy.

PMID- 8756370
TI  - Comparison of estrogen receptor determinations by a biochemical ligand-binding
      assay and immunohistochemical staining with monoclonal antibody ER1D5 in females
      with lymph node positive breast carcinoma entered on two prospective clinical
      trials.
AB  - BACKGROUND: The measurement of estrogen receptors (ER) in breast cancer specimens
      has traditionally been assessed with a dextran-coated charcoal assay (DCCA). More
      recently the immunohistochemical staining (IHC) method has gained increasing
      popularity because of its ability to use fixed tissue, assess needle biopsies,
      and reduce cost. Controversy exists over the accuracy of IHC compared with that
      of DCCA in determining ER. We compared these two techniques using tumor tissue
      obtained from a large group of females with lymph node positive breast carcinoma
      with long term follow-up. METHODS: Breast carcinoma tissue was obtained from a
      large group of females with node positive breast carcinoma participating in two
      adjuvant chemotherapy trials. ER was determined by the traditional DCCA method
      and by IHC using the ER1D5 antibody. Disease free survival (DFS) and overall
      survival (OS) were assessed by each of these methods. RESULTS: ER status was
      determined by DCCA and IHC in tumor tissue obtained from 316 females. A
      concordance of 79% was observed for the determination of ER-positive tumors. Of
      the discordant results, the majority of DCCA-negative, IHC-positive tumors could
      be explained by a low level of DCCA positivity (< 10 fmol) or IHC staining of
      nonmalignant cells. A much higher rate of discordant results was observed in
      premenopausal females. Of the DCCA-negative, IHC-positive patients 97% were
      premenopausal and of the DCCA-positive, IHC-negative patients 79% were
      premenopausal. ER by DCC appears to perform better than ER by IHC as a prognostic
      factor in terms of DFS and OS. CONCLUSIONS: When compared with DCCA, IHC with
      monoclonal antibody ER1D5 appears to be a reasonable substitute for the
      determination of ER. Although DCCA appeared to perform better as a determinant of
      prognosis, ER detection is used primarily for deciding on hormonal therapy.
      Review of discordant cases indicates IHC may more accurately reflect the ER
      status of malignant cells in some patients. Attention must be paid to quality
      control considerations in performance of IHC staining.

PMID- 8756371
TI  - Can core needle biopsy replace fine-needle aspiration cytology in the diagnosis
      of palpable breast carcinoma. A comparative study of 124 women.
AB  - BACKGROUND: There appears to be a growing movement in favor of core needle biopsy
      (CNB) over fine-needle aspiration (FNA) cytology in detecting breast carcinoma in
      women. The authors compared the sensitivity and specificity of these two methods
      in patients who presented to The University of Texas M. D. Anderson Cancer Center
      for evaluation of a palpable breast mass. METHODS: One hundred and twenty-four
      women (mean age, 51 years; range, 28-86 years) with a clinically suspicious
      palpable mass (mean size, 4.4 cm; range, 1-12 cm) underwent concurrent FNA and
      CNB. For the FNA, an average of three needle passes were made. FNA was followed
      by three CNBs using the Bard Monopty needle. CNB samples were submitted for
      frozen section to determine adequacy, and an additional three cores were
      performed if the first batch was deemed inadequate. All patients ultimately had
      histologic confirmation of their neoplasms either by the core needle procedure or
      by definitive open surgical biopsy. Features of cases with discrepant diagnoses
      were examined in relation to tumor size and histologic type. RESULTS: Specificity
      of both FNA and CNB was 100%. The sensitivity in detecting a malignant neoplasm
      was higher for FNA than for CNB (97.5% vs. 90%, P < 0.004). CONCLUSIONS: In our
      experience, FNA of palpable breast lesions is a more sensitive method for the
      detection of carcinoma regardless of tumor type, size, or differentiation.
      Contrary to other reports, not only was FNA alone more sensitive than CNB alone,
      the addition of CNB to an already negative FNA failed to increase sensitivity in
      the detection of carcinoma. However, CNB did contribute to a more definitive
      diagnosis in some cases. The authors also found FNA to be more cost effective
      than CNB for palpable breast lesions when time and effort are taken into
      consideration. This reinforces the benefit of FNA over CNB in the detection of
      early stage breast carcinoma.

PMID- 8756372
TI  - Prognostic significance of in situ carcinoma associated with invasive breast
      carcinoma. A natural experiment in cancer immunology?
AB  - BACKGROUND: Our previous studies indicate that the in situ phase of mammary
      carcinogenesis is characteristically associated with cell-mediated immunity (CMI
      against an immunogen shared by most breast carcinomas. Such reactivity is
      inversely correlated with stage and appears to impede in situ-to-invasive
      progression and lethality from invasive breast carcinoma. If in situ carcinomas
      are indeed associated with ambient, prognostically favorable immunity against
      such an immunogen, one would expect lethality from invasive breast carcinoma to
      be reduced in patients with a diagnosis of a prior, simultaneous, or subsequent
      in situ breast carcinoma. The present study provides a test of such
      relationships. METHODS: Patient survival was analyzed for 129,394 female patients
      with invasive breast carcinoma diagnosed in areas covered by the Surveillance,
      Epidemiology, and End Results (SEER) Program based at the National Cancer
      Institute (NCI). Patients were classified according to whether they had a prior,
      simultaneous, or subsequent in situ breast carcinoma and survival was examined
      for up to 15 years subsequent to diagnosis using life tables and the Cox
      regression model. RESULTS: The findings indicate that patients with an invasive
      breast carcinoma who had a prior, simultaneous, or subsequent in situ breast
      carcinoma did experience significantly better survival than comparison groups of
      patients who either did not have an associated cancer of any type, had an
      associated invasive breast carcinoma, or had an in situ or invasive cancer of non
      breast origin. CONCLUSIONS: Our prior and current observations warrant more
      direct studies of the prognostic, therapeutic, and prophylactic significance of
      the in situ carcinoma-associated type of specific CMI in breast cancer patients.

PMID- 8756373
TI  - Fadrozole hydrochloride in postmenopausal patients with metastatic breast
      carcinoma.
AB  - BACKGROUND: Fadrozole hydrochloride (CGS-16949A) belongs to the class of
      aromatase inhibitors that lowers circulating estrogen levels by inhibiting the
      conversion of androgens to estrogens, thereby causing tumor regression in
      patients with breast carcinoma. METHODS: This was a prospective, randomized,
      Phase II study of fadrozole hydrochloride in postmenopausal patients with
      metastatic breast carcinoma. The three treatment groups received, respectively,
      fadrozole hydrochloride 0.6 mg three times daily, 1 mg twice daily, and 2 mg
      twice daily orally. RESULTS: Fifty-six patients were entered on protocol and 54
      were eligible (2 patients were perimenopausal). Eight patients had received no
      prior therapy, 15 patients had received prior hormonal therapy, 5 patients had
      received prior chemotherapy, and 28 patients had received both. After 12 weeks of
      treatment, 2 complete and 3 partial responses were observed. Forty patients
      continued treatment beyond 12 weeks, and 3 additional responses were achieved.
      Thus, 8 of 56 patients responded (14% overall response rate). Responses did not
      appear to be dose-related. The median duration of response was 36 months (range,
      8-45 months). Subjective toxicity was mild to moderate and appeared more frequent
      on the 2 mg twice daily dosing schedule. No objective toxicity in laboratory
      parameters was observed. No patient had severe or life-threatening toxicity.
      Fadrozole hydrochloride plasma concentrations (obtained every 2 weeks for 12
      weeks) appeared to be dose-dependent and noncumulative. CONCLUSIONS: This study
      confirms modest activity of fadrozole hydrochloride in a heterogeneous group of
      patients with breast carcinoma treated at three different dose levels.

PMID- 8756374
TI  - The role of DNA flow cytometry in borderline malignant ovarian tumors.
AB  - BACKGROUND: The role of flow cytometric DNA analysis in predicting prognosis of
      patients with borderline malignant ovarian tumors has been controversial.
      METHODS: Fifty cases of patients with borderline malignant ovarian tumors were
      analyzed by histology and by flow cytometry on paraffin embedded tissue. Multiple
      tissue blocks and serial sections were analyzed for each tumor. The results of
      DNA analysis were correlated to clinicopathologic data. RESULTS: DNA aneuploidy
      was demonstrable in 4 cases (8%) when the most atypical section was analyzed. The
      overall rate of aneuploidy was 14% if additional blocks and serial sections were
      studied. Two patients died from tumor. One of the two patients had an initial
      diagnosis of Stage IIc mucinous borderline tumor with DNA indices (DI) of 1.12,
      1.42, and 2.04. She had a recurrence in the contralateral ovary 1 year later (DI
      = 1.83), and a second frankly malignant recurrence diffusely in peritoneum (DI =
      1.89). The other patient had an initial diagnosis of Stage IIIc mucinous
      borderline ovarian tumor with pseudomyxoma peritonei. DNA diploidy was obtained
      in all of the samples from the primary tumor. An aneuploid peak (DI = 1.28) was
      demonstrated in only one serial section of the peritoneal implants. Of the other
      5 patients who had aneuploid histograms but were disease-free, the DNA indices
      were 1.35, 1.14/1.18, 1.15, 1.20, and 1.31 and were demonstrable only in either 1
      or 2 of the blocks or unproven on serial sections. All patients with diploid
      peridiploid tumors were alive and disease free. CONCLUSIONS: Reproducible DNA
      aneuploidy of high DI may be predicting a poor outcome, whereas the significance
      of inconsistently reproducible aneuploidy of low DI remains to be determined.
      Further studies of prospective DNA analysis with adequate sampling are necessary
      to define the role of flow cytometry in patients with borderline malignant
      ovarian tumors.

PMID- 8756375
TI  - Assessment of metastases to aortic and pelvic lymph nodes in epithelial ovarian
      carcinoma. A proposal for essential sites for lymph node biopsy.
AB  - BACKGROUND: In staging epithelial ovarian carcinoma, it is necessary to assess
      the presence of lymph node metastases. However, the essential sites of selective
      lymph node biopsy have yet to be determined. METHODS: The distribution of
      metastatic aortic and pelvic lymph nodes was studied in 48 patients with positive
      lymph nodes of 110 patients with ovarian carcinoma who underwent systematic
      lymphadenectomy of the aortic and pelvic regions extending to the level of the
      renal vessels. For purpose of analysis, the lymph nodes were classified into five
      subgroups: the aortic lymph nodes above the inferior mesenteric artery (A1), the
      aortic lymph nodes below the inferior mesenteric artery (A2), the common iliac
      and sacral lymph nodes (P1), the internal and external iliac and obturator lymph
      nodes (P2), and the suprainguinal (the lowest external iliac) lymph nodes (P3).
      RESULTS: The incidence of metastases to A1, A2, P1, P2, and P3 was 79%, 71%, 46%,
      77%, and 40%, respectively. Provided that 2 of the 5 lymph node subgroups were
      selected for biopsy, the combination of A1 and P2 gave the best results in
      sensitivity (94% [45 of 48 patients]) and negative (95% [62 of 65 patients])
      predictive value for detection of lymph node metastases. CONCLUSIONS: These data
      indicate that aortic lymph nodes above the inferior mesenteric artery and the
      internal and external iliac and obturator lymph nodes are essential sites for
      selective lymph node biopsy in staging epithelial ovarian carcinoma.

PMID- 8756376
TI  - Evaluation and comparison of two new prostate carcinoma markers. Free-prostate
      specific antigen and prostate specific membrane antigen.
AB  - BACKGROUND: Two new prostate cancer markers, free-prostate specific antigen (f
      PSA) and prostate specific membrane antigen (PSMA) were recently introduced. This
      report summarizes a prospective two-year multicenter test of their diagnostic or
      prognostic capabilities. Total PSA was also measured. METHODS: There were four
      clinical groups studied: (1) 226 individuals from a screening project undergoing
      ultrasound and biopsy evaluation had markers obtained: (2) 68 patients suspected
      of having prostate cancer and undergoing 2 or more biopsies had the markers
      obtained on multiple occasions: (3) 100 patients undergoing radical prostatectomy
      had markers obtained pre- and post-operatively: and (4) 31 patients with
      metastatic prostate cancer each had multiple samples for marker assay obtained
      over a 2-year period. In all, 465 patients had one or more samples obtained and
      studied. RESULTS: Free-PSA affords little additional diagnostic advantage
      compared with total PSA in the screening population. The receiver operating
      characteristic curves for diagnostic accuracy were ranked: (1) PSA density; (2)
      total PSA; (3) f-PSA; and (4) PSMA, PSMA showed the best correlation with stage
      of the primary tumor in the screened group. In the multiple negative biopsy
      group, f-PSA varied from 12 to 21%. PSMA values were evaluated in all histologic
      categories. PSA density was > or = 0.15 in all categories. In the prostatectomy
      cases PSA values postoperatively were quite low in Stage II; f-PSA was of no
      value. Later, f-PSA was increased in association with elevated total PSA values.
      Mean PSMA values were above normal in all postoperative time periods except in
      Stage III patients at 6 months to 1 year postoperatively. PSA densities were all
      > or = 0.15. In patients with metastatic carcinoma, elevated PSMA values
      correlated best with a poor prognosis (clinical progression), as has been
      described. CONCLUSIONS: These data suggest that f-PSA values do not provide
      additional diagnostic benefit compared with total PSA in screening populations,
      in the presence of suspected cancer, postprostatectomy, or in metastatic disease.
      PSMA is of prognostic significance, especially in the presence of metastatic
      disease, and correlates well with the stage of disease in cancers detected in a
      screened population.

PMID- 8756377
TI  - Flow cytometric quantitation of the proliferation-associated nuclear antigen p105
      and DNA content in patients with renal cell carcinoma.
AB  - BACKGROUND: Although tumor stage and grade are important prognostic parameters
      for patients with renal cell carcinoma, postnephrectomy survival is often
      difficult to predict. Therefore identifying patients at high risk for disease
      progression is critical. Using two-color flow cytometry, DNA and proliferation
      associated nuclear antigen p105 contents were measured simultaneously in 75
      patients with renal cell carcinomas and the ability of these results to predict
      the survival was assessed. METHODS: Flow cytometric study of the proliferation
      associated nuclear antigen p105 was done on cancer cell suspensions from 75
      patients with renal cell carcinomas. By setting the cutoff line at the level
      between the brighter and the dimmer subpopulations in the diploid G0G1 region,
      the p105-labeling rate was calculated by the p-105DNA dual fluorescence analysis.
      RESULTS: The mean p105-labeling rate was 66.8% (median: 67.6%; range: 33.9-93%).
      The 5-year survival rate of patients with high p105-labeling tumors was
      significantly lower than that of patients with low labeling tumors (P < 0.05).
      The following factors were examined univariantly as prognostic factors: Robson's
      stage, DNA ploidy pattern, grade, and p105-labeling rate. All of these factors
      except for DNA ploidy pattern were prognostic. The Cox multivariate regression
      analysis was performed with the three statistically significant variables.
      Accordingly, these three factors were significantly associated with survival rate
      and were found to be independent prognostic factors. CONCLUSIONS: The measurement
      of p105 may provide useful information for predicting prognosis of patients with
      renal cell carcinoma.

PMID- 8756378
TI  - The proliferation index of MIB-1 as a prognostic factor for patients with
      transitional cell carcinoma of the upper urinary tract.
AB  - BACKGROUND: Recently, several reports have shown that immunohistochemical
      analysis using MIB-1 antibody, which recognizes Ki-67 (a human nuclear antigen
      expressed of proliferating cells), is a useful method for determining the
      proliferative activity of various cancers. In this study, the authors evaluated
      the prognostic usefulness of the proliferation index using MIB-1 antibody in
      transitional cell carcinoma of the upper urinary tract. METHODS: Proliferation
      activity was investigated immunohistochemically using monoclonal antibody MIB-1
      in formalin fixed, paraffin embedded tissues obtained from 67 specimens of renal
      pelvic and ureteral cancer. The MIB-1 proliferation index values were calculated
      from each sample as the percentage of positive nuclei expressed in tumor cells
      and the clinicopathologic correlation evaluated. RESULTS: The MIB-1 proliferation
      index values were correlated with prognostic parameters such as pathologic stage
      ( < or = pT1 vs. > or = pT2, P < 0.0005), histologic grade (G1 vs. G2, P < 0.01;
      G1 vs. G3, P < 0.0001; G2 vs. G3, P < 0.001), and prognosis (P < 0.0001). When
      patients were subgrouped using index values, patients with higher indices ( > or
      = 24%) had significantly poorer survival (P < 0.0001). This was especially
      observed in the G2 group, in which 9 of 10 patients in the higher indices
      subgroup had a high incidence of recurrence and died. In contrast, only 2 of 29
      patients in the lower indices subgroup died. The higher indices subgroup had
      significantly worse cause specific survival (P < 0.0001). Furthermore, with
      regard to the muscle invasive tumors ( > or = pT2), the higher indices subgroup
      also had significantly worse cause specific survival (P < 0.0001). CONCLUSIONS:
      The results of the evaluation of prognostic parameters indicate that the MIB-1
      proliferation index is a useful prognostic factor and may enhance the accuracy of
      conventional morphologic grading and pathologic staging systems.

PMID- 8756379
TI  - Postarthroplasty histiocytic lymphadenopathy in gynecologic oncology patients. A
      benign reactive process that clinically may be mistaken for cancer.
AB  - BACKGROUND: A distinctive histiocytosis occurs in the regional draining lymph
      nodes after large joint replacements, resulting in lymphadenopathy that may mimic
      cancer both grossly and microscopically. Postarthroplasty histiocytic
      lymphadenopathy has most often been observed in males during surgery for prostate
      cancer. METHODS: The authors present three examples of postarthroplasty
      histiocytic lymphadenopathy that occurred in gynecologic oncology patients. We
      studied the clinical, histologic, and immunohistochemical features of all three
      cases and the ultrastructure of one of them. RESULTS: Most involved lymph nodes
      were enlarged, but histiocytosis was also seen in normal sized lymph nodes.
      Microscopically, histiocytes with abundant granular cytoplasm were present in the
      lymph node parenchyma, and, to a lesser extent, in the sinuses. Normal lymph node
      architecture was variably effaced and the histiocytic infiltrate extended focally
      into the perinodal tissue. Small, black metal particles were present in the
      histiocytes in every case. Birefringent polyethylene particles were a prominent
      finding in all three cases as confirmed by positive modified oil red O staining,
      and, in one case, by electron microscopy. The histiocytes were strongly
      immunoreactive for CD68, but immunostains for S100 protein, MAC 387, and
      cytokeratin were negative. CONCLUSIONS: Enlargement of the lymph nodes in cancer
      patients who have had large joint replacements may be due to a benign
      histiocytosis rather than to metastatic cancer. The histologic features of the
      lymphadenopathy are distinctive and recognizable in routine histologic
      preparations. Polyethylene wear particles shed from joint prostheses are the most
      common substances in the histiocytes and are the most likely cause of the
      histiocytosis.

PMID- 8756380
TI  - Intraabdominal desmoplastic small cell tumor. Report and discussion of five
      cases.
AB  - BACKGROUND: Intraabdominal desmoplastic small cell tumor is a rare malignancy
      that has only recently been described. In the adult population, it is usually
      seen in young males. The tumor appears to arise as a dominant mass or masses in
      the abdominal cavity, particularly in the pelvic region, without a clear visceral
      origin. Multiple small tumor nodules may be found attached to the peritoneal
      surface. Visceral metastases occur late in the clinical course, ultimately
      leading to the patient's death. Five young adults with intraabdominal
      desmoplastic small cell tumors were treated with aggressive chemotherapy.
      METHODS: Charts of five patients treated between 1990 and 1995 were reviewed. The
      diagnosis of desmoplastic small cell tumor was made on the basis of typical
      clinical and radiographic findings, light microscopy showing hyperchromatic cells
      surrounded by a desmoplastic stroma, and immunohistochemistry demonstrating
      markers of epithelial and mesenchymal differentiation. Patients were treated with
      aggressive combination chemotherapy consisting of alternating regimens similar to
      those used as testis cancer salvage therapy. RESULTS: Four of the five patients
      demonstrated a partial response to chemotherapy. Two of the responding patients
      had surgery with the intent of removing all residual disease, but this was
      successful in only one case. All patients have died from their cancer.
      CONCLUSIONS: Intraabdominal desmoplastic small cell tumors are sensitive to
      combination chemotherapy. It appears that treatment offers good palliation and
      may prolong survival in isolated cases. However, even the patients managed with
      the most aggressive medical and surgical approaches are not cured and ultimately
      die of their disease.

PMID- 8756381
TI  - Opioid rotation in patients with cancer pain. A retrospective comparison of dose
      ratios between methadone, hydromorphone, and morphine.
AB  - BACKGROUND: When a change of opioid is considered, equianalgesic dose tables are
      used. These tables generally propose a dose ratio of 5:1 between morphine and
      hydromorphone. In the case of a change from subcutaneous hydromorphone to
      methadone, dose ratios ranging from 1:6 to 1:10 are proposed. The purpose of this
      study was to review the analgesic dose ratios for methadone compared with
      hydromorphone. METHODS: In a retrospective study, 48 cases of medication changes
      from morphine to hydromorphone, and 65 changes between hydromorphone and
      methadone were identified. the reason for the change, the analgesic dose, and
      pain intensity were obtained. RESULTS: The dose ratios between morphine and
      hydromorphone and vice versa were found to be 5.33 and 0.28, respectively
      (similar to expected results). However, the hydromorphone/methadone ratio was
      found to be 1.14:1 (5 to 10 times higher than expected). Although the dose ratios
      of hydromorphone/morphine and vice versa did not change according to a previous
      opioid dose, the hydromorphone/methadone ratio correlated with total opioid dose
      (correlation coefficient = 0.41 P < 0.001) and was 1.6 (range, 0.3-14.4) in
      patients receiving more than 330 mg of hydromorphone per day prior to the change,
      versus 0.95 (range, 0.2-12.3) in patients receiving ae330 mg of hydromorphone per
      day (P = 0.023). CONCLUSIONS: These results suggest that only partial tolerance
      develops between methadone and hydromorphone. Methadone is much more potent than
      previously described and any change should start at a lower equivalent dose.

PMID- 8756382
TI  - Trilateral retinoblastoma. A report of five patients.
AB  - BACKGROUND: Trilateral retinoblastoma is a well recognized, although rare,
      syndrome. Most of the reported cases have involved a family history of
      retinoblastoma (RB) and the disease is almost always fatal. The authors chose to
      investigate the cases of trilateral retinoblastoma occurring in the West
      Midlands, a region of the United Kingdom with an increasing incidence of
      bilateral sporadic RB. METHODS: Five patients with trilateral retinoblastoma
      (including two were previously reported), diagnosed in 146 consecutive patients
      with RB in the West Midlands Health Authority Region between 1957 and 1994, are
      presented (an incidence of 3%). Their clinical presentation, treatment, and
      outcome are described. RESULTS: There were 4 patients with pineoblastoma, only
      one of whom had a positive family history. The mean age at diagnosis of RB and 6
      months, whereas the patients with pineoblastoma were diagnosed at a mean age of 2
      years 8 months. The tumors were not evident on the initial computed tomography
      scans. One child presented with a calcified suprasellar mass 13 months before the
      bilateral sporadic RB was identified. Death occurred within 1 month of diagnosis
      of the intracranial tumor in 3 patients who did not receive any treatment. In the
      other 2 patients who were treated, death occurred at 15 months and 2 years 7
      months, respectively, after diagnosis of intracranial tumor. CONCLUSIONS: Early
      diagnosis with regular neuro-imaging and more aggressive treatment may improve
      prognosis in patients with RB and an intracranial tumor.

PMID- 8756383
TI  - Magnetic resonance imaging changes after stereotactic radiation therapy for
      childhood low grade astrocytoma.
AB  - BACKGROUND: Stereotactic radiotherapy (SRT) is fractionated radiotherapy
      delivered under stereotactic guidance to produce highly focal and precise
      therapy. We studied the incidence of imaging changes that can mimic tumor
      progression after completion of SRT for childhood low grade astrocytoma. METHODS:
      Between June 1992 and September 1994, we prospectively treated 28 children with
      low grade astrocytomas with SRT. The patients ranged in age from 2 to 22 years
      (median: 10 yrs) and none had received prior radiation therapy or radiosurgery.
      Routine fractionation was employed (180-200 centigray[cGy]) to a total dose of
      5220-6000 cGy over 5 to 6 weeks. All of the patients underwent initial and follow
      up magnetic resonance imaging (MRI) according to protocol. RESULTS: Median
      clinical follow-up for the 28 patients was 24 months (range, 5-32 mos) with a
      median radiographic follow-up of 15 months (range, 3-26 mos). Fifteen patients
      had reduction in tumor size, one patient had stable disease. Twelve patients
      (43%) developed increased size of the lesion, increased signal intensity or
      enhancement, cysts or cavitations, and an increase in edema or mass effect on
      follow-up MRI. Most of these changes occurred between 9 and 12 months after the
      start of SRT and resolved or decreased by 15 to 21 months. All but one patient
      had normal or stable neurologic examinations. CONCLUSIONS: Treatment-related MRI
      changes are common after conventionally fractionated schedules using stereotactic
      radiation techniques for patients with low grade astrocytomas. These changes can
      be distinguished from tumor progression by their transient nature as well as the
      general absence of clinical symptoms.

PMID- 8756384
TI  - Is there a correlation between duration of presenting symptoms and stage of
      medulloblastoma at the time of diagnosis?
AB  - BACKGROUND: Does a "delay in diagnosis" lead to a child being diagnosed with
      advanced stage as opposed to early stage medulloblastoma? Correlation between the
      duration of a patient's presenting symptoms and stage at diagnosis was examined.
      METHODS: The population consisted of 72 consecutive patients with histologically
      proven medulloblastoma diagnosed between July 1, 1983 and July 31, 1995. A
      standard history and physical examination format was used to record the nature
      and duration of presenting symptoms. Patients were staged by use of the operative
      findings, pre- and postoperative cranial computed tomography (CT) scans and,
      later in the series, cranial magnetic resonance imaging (MRI) studies and, for
      determination of the M stage, myelography, spinal MRI, and postoperative
      cerebrospinal fluid cytology. RESULTS: There were 40 males (56%) and 32 females
      (44%) with a mean age of 11.8 years. The most common presenting symptoms were
      vomiting (67%), headache (60%), ataxia (40%), and nausea (39%). By the Chang
      Harisiadis (CH) system, 39 patients (54%) were found to have high stage
      medulloblastoma (T3b-4M0 or any TM1-4), 27 (38%) had low stage disease (T1-3aM0),
      and in 6 (8%) the stage could not be fully determined. By the Langston
      modification of the Change-Harisiadis system (LCH) 38 patients (54%) had high
      stage, 24 (32%) had low stage, and in 10 (14%) the stage could not be fully
      determined. Fifty of the 66 patients for whom the duration of symptoms was known
      (76%) had < or = 3 months of symptoms prior to stage. High CH stage patients had
      a mean duration of symptoms of 7.4 +/- 6.9 weeks versus 19.5 +/- 22.5 weeks for
      low stage patients. (P < 0.001). High LCH stage patients had a mean duration of
      symptoms of 7 +/- 6.6 weeks versus 15.4 +/- 16.4 weeks for low stage patients (P
      < 0.01). Patients ultimately found to have MO disease were diagnosed more slowly
      (16.1 +/- 20 weeks) than those with M1 (7.3 +/- 5.3 weeks), M2 (6 +/- 5.3 weeks),
      or M3 disease (6.8 +/- 5.9 weeks) M0 vs. M1-3, P < 0.02). No patients had M4
      disease. Using an alternative definition of high versus low stage (T4M0 or any
      TM1-4 vs. T1-3bM0) currently under consideration by pediatric oncologists, the
      duration of symptoms remained significantly longer for low stage disease in the
      CH system (high vs. low, 7.2 +/- 5.8 weeks vs. 17.5 +/- 19.1 weeks, P < 0.01) but
      not in the LH system (high vs. low, 10.6 +/- 16.1 weeks vs. 13.9 +/- 15.9 weeks,
      P not significant). CONCLUSIONS: A short duration of symptoms is associated with
      the diagnosis of more advanced medulloblastoma. This finding has significant
      potential implications for the identification of prognostic groups in
      medulloblastoma as well as medical-legal claims of "delay in diagnosis" and
      capitated health care issues.

PMID- 8756385
TI  - DNA index of glial tumors in children. Correlation with tumor grade and
      prognosis.
AB  - BACKGROUND: Although DNA index (DI) has prognostic significance in a variety of
      pediatric malignancies, there are few data regarding its utility in central
      nervous system (CNS) tumors. We have previously shown that patients with
      hyperdiploid medulloblastoma have a significantly better survival than those
      whose tumors are diploid. Here, we examine the effect of DI and tumor grade on
      the progression free survival (PFS) of 57 patients with a variety of glial
      neoplasms. METHODS: DI was determined by flow cytometry on freshly obtained tumor
      tissue from the initial diagnostic specimens; a DI = 1.0 was defined as diploid
      (DIP), 1.0 < DI < 1.1 as near diploid (NDIP), and DI > 1.1 as hyperdiploid (HYP).
      Tumors were histologically graded according to the World Health Organization
      classification. RESULTS: There were 21 Grade I tumors, 20 Grade II, 8 Grade III,
      and 8 Grade IV. Among the 41 low grade tumors (Grade I-II), 39 were DIP or NDIP,
      and 2 were HYP. Among the 16 high grade tumors (Grade III-IV), 9 were DIP, 2
      NDIP, and 5 HYP. The 4-year PFS of low grade tumors was 70% (standard deviation
      [SD] 12%) versus 8% (SD 7%) for high grade tumors. There was a significant
      correlation between low grade tumor histology and a DIP/NDIP DI (P = 0.015), and
      univariate analysis suggested improved PFS was associated with DIP/NDIP tumors (P
      = 0.05). However, DI did not remain a significant prognostic factor after being
      stratified by tumor grade (P = 0.87). CONCLUSIONS: Unlike medulloblastoma, DI is
      not an independent prognostic factor in pediatric glial tumors.

PMID- 8756386
TI  - Uterine anomalies in Wilms' tumor survivors.
AB  - BACKGROUND: The association between Wilms' tumor (WT) and genitourinary (GU)
      anomalies has long been appreciated; however, associated GU anomalies have been
      described almost exclusively in males. METHODS: To investigate whether females
      with WT also have an increased prevalence of GU anomalies, the authors evaluated
      the uterine anatomy of 24 WT survivors using magnetic resonance imaging and
      ultrasonography. RESULTS: Two of 24 female survivors (8%) had anomalies. One had
      a septate uterus, and a limited molecular analysis of her constitutional DNA
      revealed no mutations or deletions of the tumor suppressor gene WT1. Another
      survivor with the WAGR syndrome (WT, aniridia, GU anomalies, and retardation),
      with the characteristic 11p13 deletion including WT1, had a uterine anomaly
      (hypoplastic vs. unicornuate). CONCLUSIONS: Because uterine malformations are
      rare in the general population, this finding suggests an association between WT
      and uterine malformations and also may partially explain the fertility deficit
      previously demonstrated in adult female WT survivors. Pelvic ultrasonography in
      adult female WT survivors can alert survivors and clinicians to possible
      fertility problems that may lead to problem pregnancies and adverse pregnancy
      outcomes.

PMID- 8756388
TI  - Ifosfamide and etoposide plus vincristine, doxorubicin, and cyclophosphamide for
      newly diagnosed Ewing's sarcoma family of tumors.
AB  - BACKGROUND: This study was conducted to determine the feasibility of, and improve
      outcome by, incorporating ifosfamide and etoposide (IE) into the therapy of newly
      diagnosed patients with Ewing's sarcoma family of tumors of bone and soft tissue.
      METHODS: Fifty-four newly diagnosed patients received 7 cycles of vincristine,
      doxorubicin, and cyclophosphamide (VAdriaC) and 11 cycles of IE. Radiation
      therapy after the fifth chemotherapy cycle was the primary approach to local
      control. RESULTS: Actuarial 5-year event-free survival (EFS) and overall survival
      rates were 42% and 45%, respectively, with a median duration of potential follow
      up of 6.8 years. EFS was significantly better for patients with localized tumors
      than for those with metastatic lesions (64% v. 13%, P < 0.0001). Actuarial local
      progression-free survival at 5 years was 74%, and did not correlate with primary
      tumor size or site, histologic subtype, or the presence of metastases. Febrile
      neutropenia developed after 49% of cycles, and clinical or sub-clinical cardiac
      dysfunction was common (7% and 40% respectively). There were four toxic deaths
      and one case of secondary myelodysplastic syndrome. CONCLUSIONS: Despite
      substantial toxicity, the integration of IE into the front-line, VAdriaC-based
      therapy of patients with Ewing's sarcoma family of tumors is feasible and
      appeared to significantly improve the outcome for patients with high risk
      localized tumors, but had no impact on the poor prognosis of patients with
      metastatic tumors. Local control can be achieved in the vast majority of patients
      using radiotherapy exclusively, even among patients with bulky, central axis
      tumors. Longer follow-up is needed to evaluate the late effects of this intensive
      therapy.

PMID- 8756387
TI  - Significance of surgical margin on the prognosis of patients with Ewing's
      sarcoma. A report from the Cooperative Ewing's Sarcoma Study.
AB  - BACKGROUND: There is little information regarding an adequate surgical margin for
      local control of Ewing's sarcoma. METHODS: Two hundred and forty-four patients
      (PTS) with Ewing's sarcoma who were registered in the Cooperative Ewing's Sarcoma
      Studies underwent surgical treatment. Ninety-four PTS underwent definitive
      surgery (surgery alone), 131 PTS received postoperative irradiation, and 19 PTS
      received preoperative irradiation. The surgical margins were distributed as
      follows: radical, 29 PTS; wide, 148 PTS; marginal, 39 PTS; and intralesional, 28
      PTS. The impact of the surgical margin on the treatment outcome of PTS was
      analyzed statistically. RESULTS: The local or combined (local recurrence and
      systemic metastasis) relapse rate after surgery with or without irradiation was
      significantly lower compared with that after definitive irradiation (irradiation
      alone) (7% vs. 31%, P < 0.0001). The local or combined relapse rate after
      complete resection (radical or wide margin) with or without irradiation was less
      compared with that after incomplete resection (marginal or intralesional margin)
      with or without irradiation (5% vs. 12% P = 0.0455). The local or combined
      relapse rate did not greatly decreased after irradiation after incomplete surgery
      (from 14% to 12%). In both groups of good (viable tumor cells < 10%) and poor
      (viable cells > or = 10%) histologic response, the difference in systemic or
      combined relapse rate between patients undergoing complete and incomplete surgery
      was not significant. The 10-year overall survival of the PTS for each of the
      margins was distributed as follows: radical, 58%; wide, 65%; marginal, 61%; and
      intralesional, 71% (P = not significant). CONCLUSIONS: Surgery in patients with
      Ewing's sarcoma adds to the safety of local control. Under the current treatment
      regimen with intensive chemotherapy and irradiation, complete resection of the
      tumor appears capable of decreasing the risk of local recurrence.

PMID- 8756389
TI  - Pericardial angiosarcoma after mediastinal irradiation for seminoma. A case
      report and a review of the literature.
AB  - BACKGROUND: Second malignancies are a well recognized complication of radiation
      therapy. METHODS: We performed a computer search of the literature using the
      Medline Database for Pericardial Tumors and Post-Irradiation Sarcomas. RESULTS:
      The case history of a patient who developed a radiation-induced pericardial
      angiosarcoma is described. We present a detailed review of pericardial sarcomas.
      CONCLUSIONS: We believe this to be the first report of a radiation-induced
      pericardial sarcoma. The importance of continued long-term observation for
      patients who receive mediastinal irradiation is stressed.

PMID- 8756390
TI  - The National Cancer Data Base. Report on colon cancer.
AB  - BACKGROUND: Commission on Cancer data from the National Cancer Data Base (NCDB)
      report time trends in stage of disease, treatment patterns, and survival for
      patients with selected cancers. The most current data (1993) for patients with
      colon cancer are described. METHODS: Five calls for data yielded 3,700,000 cases
      of cancer for the years 1985 through 1993 from hospital cancer registeries across
      the U.S., including 36,937 cases of colon cancer from 1988 and 44,812 from 1993.
      RESULTS: Interesting trends are as follows: (1) the elderly ( > 80 years) present
      with earlier stage disease than younger patients; (2) the National Cancer
      Institute recognized cancer centers have more patients with advanced disease than
      other types of hospitals; (3) all ethnic groups have generally similar stages of
      disease at presentation, except for African-Americans who have a slightly higher
      incidence of Stage IV disease; (4) the proximal migration of the primary cancer
      continues with 54.7% of primary colon cancer arising in the right colon in 1993
      compared with 50.9% in 1988; (5) an interaction between grade and stage of cancer
      seems present; and (6) patients with Stage III colon cancer who received adjuvant
      chemotherapy had a 5% improvement in 5-year relative survival. CONCLUSIONS: The
      NCDB data are useful for reporting what cancer treatments are being administered
      and what outcomes are occurring in the U.S. The data suggest an important
      biologic role for grade of cancer. They also suggest that African-Americans and
      other ethnic groups have the same outcome as non-Hispanic whites but that access
      to medical care may still be less. Finally, the utility of adjuvant therapy for
      Stage III colon cancer may just be beginning to be appreciated.

PMID- 8756391
TI  - Practice protocol for the examination of specimens removed from patients with
      ovarian tumors. A basis for checklists. Members of the Cancer Committee, College
      of American Pathologists, Task Force on the Examination of Specimens Removed from
      Patients with Ovarian Tumors.

PMID- 8756392
TI  - Purification and characterization of two acetyl xylan esterases from Penicillium
      purpurogenum.
AB  - Penicillium purpurogenum produces several enzymes active in xylan hydrolysis, of
      there, the acetyl xylan esterase (AXE) activity secreted by the fungus has now
      been studied. The amount of activity obtained in the culture is related to the
      degree of acetylation of the carbon source used, the best being chemically
      acetylated xylan. AXE was concentrated from culture supernatants by
      ultrafiltration and (NH4)2SO4 precipitation and fractionated by gel filtration in
      Bio-Gel P-300. Two peaks of activity (AXE I and AXE II) were obtained. These two
      enzymes were further purified separately to homogeneity by chromatography in CM
      Sephadex C-50 and chromatofocusing. AXE I (M(r) 48,000) has a pl of 7.5, while
      AXE II (M(r) 23,000) has a pl of 7.8. Optimal enzyme activity was at pH 5.3 and
      50 degrees C for AXE I and pH 6.0 and 60 degrees C for AXE II. Both enzymes are
      active towards several acetylated substrates. Antisera against the two enzymes do
      not cross-react, and the N-terminal sequences of AXE I and II do not show
      similarities. These results suggest that AXE I and AXE II are the products of
      different genes.

PMID- 8756393
TI  - Attachment of antibody to biotinylated red blood cells: immuno-red blood cells
      display high affinity to immobilized antigen and normal biodistribution in rats.
AB  - Streptavidin-mediated attachment of biotinylated antibodies (b-Ab) to
      biotinylated red blood cells (b-RBC) is useful for preparation of immuno-red
      blood cells, a prospective vehicle for drug targeting. However, streptavidin (SA)
      induces lysis of extensively biotinylated RBC by complement due to cross-linking
      and inactivation of RBC complement regulators. To reduce cross-linking of RBC
      membrane proteins, we utilized mild biotinylation of RBC with 20 microM biotin
      ester (b20-RBC). SA effectively binds to rat b20-RBC (10(5) SA molecules/cell)
      and provides for following attachment of 5 x 10(4) molecules of b-IgG/SA per b20
      RBC. By in vitro assay, b-Ab/SA/b20-RBC were stable in fresh rat serum. Serum
      stable immuno-red blood cells (b-Ab/SA/b20-RBC) specifically bound to antigen
      coated surfaces, but not to BSA-coated surfaces. Biodistribution of 51Cr-labelled
      b-Ab/SA/b20-RBC in rats was similar to that of control RBC, with no indication of
      lysis in vivo. These results suggest b-Ab/SA/b20-RBC may be explored as a vehicle
      for drug targeting.

PMID- 8756394
TI  - Characterization of aggregates of recombinant human factor VIII by size-exclusion
      chromatography and immunoassay.
AB  - The presence of aggregates of Factor VIII (FVIII) was assessed for a highly
      purified form (rFVIII) and for the formulated preparation containing human serum
      albumin (rFVIIIf). Size-exclusion chromatography (SEC) on Sepharose CL-6B and TSK
      4000 matrices under native conditions revealed < 1% aggregates of FVIII in either
      rFVIII or rFVIIIf, as determined by FVIII immunoassay of chromatographic
      fractions. No degradation products were observed. The immunoassay was capable of
      detecting FVIII immunoreactivity to levels of approximately 5 ng/ml. Overlap of
      FVIII clotting (FVIII:c) and immunoassay (FVIII:cAg) activities was observed for
      SEC fractions. Heat stressing of rFVIIIf (47.5 degrees C for 24 h) resulted in a
      quantitative increase in FVIII-positive material in the void volume of a TSK 4000
      column, demonstrating that aggregates of FVIII can be produced and detected by
      this method. We conclude that aggregates of FVIII in rFVIII and rFVIIIf
      constitute < or = 1% by the method described.

PMID- 8756395
TI  - In vitro immunization of murine lymphocytes using immobilized immunogens.
AB  - Murine splenic lymphocytes were immunized in vitro using immobilized antigens.
      Immobilization was achieved by covalently linking the antigens to Sepharose
      beads. Tetanus toxoid (TT) was used as test antigen in soluble and immobilized
      forms. The outcome of in vitro immunization was assayed in terms of the number of
      antigen-specific antibody-forming cells (AFCs) enumerated by filter immuno plaque
      assay. The AFC specific to TT were significantly higher in cultures stimulated
      with immobilized antigen as compared with soluble antigen. The effect of various
      concentrations of antigen, time kinetics, effect of serum, and leucyl-leucine O
      methyl ester treatment on the in vitro-immunization system has been studied. The
      results indicate that immobilized antigens are more potent than their soluble
      counterparts in vitro and hence are useful in in vitro-immunization protocols.

PMID- 8756396
TI  - Internalization and distribution of inositol hexakisphosphate in red blood cells.
AB  - Inositol hexakisphosphate (InsP6), an allosteric effector of haemoglobin, is able
      to modify the oxyhaemoglobin dissociation curve. The rightwards shift of the
      curve increases the in vivo oxygen delivery to tissues. Such an exogenous
      substance may be internalized into red blood cells (RBC) using a reversed lysis
      resealing process following a hypoosmotic shock, resulting in InsP6-RBC with
      modified oxygen transport capacity. The efficacy of the process depends on
      various physicochemical parameters which can be fixed during the experimental
      protocol. The variability of InsP6 internalization from one sample to another
      appeared to be mainly due to the natural variation in osmotic fragility of RBC.
      This factor was also modified during the storage of RBC units before the lysis
      resealing process. The separation of InsP6-RBC on a density gradient revealed a
      wide heterogeneity of internalized InsP6 concentration, varying with the degree
      of osmotic shock. The control of these various parameters will result in resealed
      InsP6-RBC in reproducible conditions suitable for in vivo use.

PMID- 8756398
TI  - Structural determinants of cobrotoxin for binding to an enzyme-linked-immunoassay
      plate.
AB  - In order to assess the manner in which the structural state of a protein affects
      the results of an ELISA, the antigenic reactivities of cobrotoxin and reduced and
      S-carboxymethylated (RCM-) cobrotoxin with anti-RCM-cobrotoxin antibodies were
      studied. The results of competitive enzyme-linked immunoassay showed that the
      affinity of RCM-cobrotoxin for anti-RCM-cobrotoxin antibodies was higher than
      that of cobrotoxin. However, the cobrotoxin-coated wells had a greater reactivity
      towards anti-RCM-cobrotoxin antibodies than against RCM-cobrotoxin-coated wells.
      The lower reactivity observed with RCM-cobrotoxin-coated plates could be improved
      by adding 0.01% glutaraldehyde during the coating procedure. Studies on the
      antigenic structures of RCM-cobrotoxin showed that it contained an immunodominant
      epitope at residues 22-38. Moreover, the N-terminal and C-terminal regions of RCM
      cobrotoxin encompassed other antigenic determinants which exhibited low
      reactivities towards anti-RCM-cobrotoxin antibodies. After removal of the
      antibodies against residues 22-38 of cobrotoxin from anti-RCM-cobrotoxin
      antibodies by passage through an affinity column, the remaining antibodies
      exhibited a similar reactivity towards cobrotoxin and RCM-cobrotoxin. The
      antibodies against residues 22-38 retained a little reactivity with the RCM
      cobrotoxin-coated wells. These results suggest that the structural determinants
      of cobrotoxin and RCM-cobrotoxin for binding to the microtitre plates differ.
      Unlike RCM-cobrotoxin, the loop II structure of cobrotoxin encompassing residues
      22-38 is not exclusively involved in the binding of cobrotoxin to microtitre
      plates.

PMID- 8756397
TI  - Production, purification and characterization of an anti-(carcinoembryonic
      antigen) recombinant single-chain Fv antibody fragment.
AB  - Specific targeting of radioactive agents to tumour cells has been the main
      objective of the in vivo use of monoclonal antibodies and their fragments. In
      particular, specific antibodies to carcinoembryonic antigen (CEA)-expressing
      tumours can be used either for diagnosis or therapy, if targeting could be
      improved. The expression of antibody fragments in bacteria allows the preparation
      of engineered molecules with antigen-binding properties and a better penetration
      into the tumour. A specific anti-CEA single-chain Fv fragment was produced in
      bacteria and purified. Its binding activity has been demonstrated in ELISA,
      immunocytochemistry, immunohistochemistry, fluorescence-activated cell sorting
      and the kinetic parameters determined by the plasmon surface resonance.

PMID- 8756399
TI  - [Long-term follow-up of the etiology of diarrhea with emphasis on the role of
      rotaviruses in hospitalized patients at the Infectious Disease Clinic of the
      Medical School Hospital in Plzen].
AB  - During 1986-1994 the etiological structure of diarrhoea in hospitalized patients
      at the Infectious Diseases Clinic, University Hospital Plzen was analyzed. In
      children under four years most frequently (in 26%) rotaviruses were involved, in
      older patients their ratio was lower and the decisive pathogenetic organism were
      salmonellae. In rotavirus infections the shortest hospitalization period was
      recorded. These infections were encountered all round the year with a maximum
      prevalence in the winter months.

PMID- 8756400
TI  - [ELISA in the determination of antiphosphatidylserine antibodies].
AB  - Antiphospholipid antibodies (APA) are a group of antibodies against various
      phospholipid antigens. In order to extend the spectrum of examined specificities
      of antiphospholipid antibodies the authors elaborated an ELISA method for
      assessment of antiphosphatidyl serine antibodies (APSA). As antigen they used
      phosphatidyl serine isolated from the white matter of cattle brain. The ELISA
      method was tested by examining APSA in 12 patients with rheumatic diseases, 24
      women with reproductive disorders and 50 patients with testicular tumours and the
      results were compared with examinations of anticardiolipin antibodies. The
      concurrent presence of both types of antibodies was recorded in 20.8% women with
      reproductive disorders and in 14% of the patients with testicular tumours. In
      these groups antiphosphatidyl serine antibodies were found more frequently.

PMID- 8756401
TI  - [Postantibiotic effects and postantibiotic effects of subinhibitory levels of
      quinolines on Pseudomonas aeruginosa].
AB  - The postantibiotic effect (PAE) (PA phase induced by 2x or 4x MIC) and
      postantibiotic effect of subinhibitory concentrations (PA SME) of three
      quinolones-enoxacin, norfloxacin and pefloxacin against Pseudomonas aeruginosa
      were determined. It was observed that the tested antibiotics at suprainhibitory
      concentrations 2x MIC induced PAEs of 2.1-6.7 h. Longer PAEs were observed after
      treatment with antibiotics at concentration 4x MIC (4.1-9.0 h). Subinhibitory
      concentrations of quinolones added to bacterial suspensions in the postantibiotic
      phase (2x or 4x MIC) displayed longer delay of bacterial regrowth (PA SMEs)
      compared to PAEs. No regrowth of bacterial culture was observed even at 48 h in
      the case of pefloxacin (2x MIC + 0.3x MIC, 4x MIC +0.2x MIC, 4x MIC + 0.3x MIC)
      as well as norfloxacin (4x MIC + 0.2x MIC, 4x MIC + 0.3x MIC).

PMID- 8756402
TI  - [Cytotoxicity and invasive virulence of Yersinia enterocolitis strains in various
      mammalian cell lines].
AB  - The authors tested the suitability of 10 cell lines for assessment of the
      virulence of strains of Yersinia enterocolitica by the cytotoxicity test. Line
      LLC-MK2, HEp-2, HeLa, L-132 and L929 are most suitable. Lines LEP, 3T3, MDCK and
      McCoy are usable, line BHK-21 is unsuitable. On the same cell lines also the
      invasiveness of the virulent and non-virulent strains of Y. enterocolitica was
      assessed. For detection of the internalization of bacteria a modified method of
      double fluorescent staining was used which is simpler and more rapid. The
      invasiveness, similarly as the cytotoxicity of the virulent strain was proved on
      all tested cell lines, contrary to the non-virulent strain which was neither
      cytotoxic nor invasive. Using strains of Y. enterocolitica, isolated from faeces
      of patients with diarrhoea of infectious etiology or another bowel disease and
      from water, the cytotoxicity method was compared with recommended biochemical
      virulence tests used in this country: bond with Congo red, crystal violet,
      dependence on Ca2+ and pyrazinamidase activity. Strains of serotype 0:5, 0:6.31
      and 0:7.8 biotype 1 gave in all tests negative results, strains of serotype 0:3
      biotype 4 differed. The highest number of positive strains was detected by the
      cytotoxicity test. The positivity of strains of this serotype was assessed by the
      invasiveness test in vitro. The cytotoxicity test was thus proved to be a very
      effective, rapid and easy test of detection of the virulence of Y. enterocolitica
      strains.

PMID- 8756403
TI  - [Treatment of infectious complications affecting the skin and soft tissues with
      cefpodoxime proxetil].
AB  - The authors present their experience with antimicrobial treatment with
      cephalosporin of the third generation, cefpodoxime proxetil, in skin and soft
      tissue infections in a group of patients treated at the ambulatory department of
      the Surgical Clinic in Prague 10 in 1995. From the total number antimicrobial
      treatment was administered to 6 patients with a phlegmon, 5 patients with
      panaritium, 4 patients with an early infection after laparotomy, 3 with an
      abscess in the subcutaneous layer, and with cheilitis and bursitis of the
      olecranon in the remaining two patients. In addition to surgical treatment
      (incision, evacuation and drainage) cefpodoxime proxetil-200 mg after 12-hour
      intervals for 6-9 days-was administered to the patients. For microbiological
      examination a smear from the inflammatory focus and from the nasopharynx was
      used. The cefpodoxime proxetil serum level was assessed during the 1st-11th hour
      after administration of the antibiotic. All 20 patients recovered.

PMID- 8756404
TI  - [Identification and typing of hospital strains of Acinetobacter calcoaceticus
      Acinetobacter baumanni complex].
AB  - A collection of 95 strains of the Acinetobacter calcoaceticus-Acinetobacter
      baumannii complex, isolated between 1991 and 1993 in the Prague Burn Center (BC),
      was studied. Ninety-one strains were isolated from 43 patients: 50 of them from
      burnt sites, 22 from endotracheal tube, 13 from urine, 3 from blood and 3 from
      venous catheter, and 4 strains were isolated from the hospital environment and
      the nursing staff. The strains were classified by restriction endonuclease
      fingerprinting of total DNA, plasmid profile analysis, ribotyping, comparison of
      antibiograms, biotyping and according to epidemiological data, into 31
      relatedness groups each of them including 1 to 29 strains, likely to be isolates
      of the same strain. None of the methods used enabled to distinguish all groups.
      The importance of the polyphasic approach is emphasized since three
      multiresistant strains, isolated almost simultaneously in the BC, needed at least
      two methods to be distinguished (e.g. ribotyping and biotyping). Twenty-eight
      representative strains of different groups were identified by ribotyping: 18 of
      them were allocated to genomospecies 2 (A. baumannii), 5 to genomospecies 3 and 5
      to genomospecies 13 sensu Tjernberg and Ursing. Only A. baumannii was found to
      spread among patients. Strains of two multiresistant groups persisted in the BC
      throughout the period studied and strains of one of these groups were responsible
      for an outbreak in the autumn of 1993. The methods mentioned above were used to
      describe 12 multiresistant strains isolated in three hospital wards in other
      localities. When ribotyped these strains were identified as A. baumannii. The
      strains of the same origin were identical in their typing profiles while the
      strains of different origins were easy to differentiate using any of the above
      methods; nevertheless, 2 of these groups were almost identical to 2 groups of
      multiresistant strains isolated in the BC.

PMID- 8756405
TI  - Selecting apt RNAs for NMR.

PMID- 8756406
TI  - Solution structure of an ATP-binding RNA aptamer reveals a novel fold.
AB  - In vitro selection has been used to isolate several RNA aptamers that bind
      specifically to biological cofactors. A well-characterized example in the ATP
      binding RNA aptamer family, which contains a conserved 11-base loop opposite a
      bulged G and flanked by regions of double-stranded RNA. The nucleotides in the
      consensus sequence provide a binding pocket for ATP (or AMP), which binds with a
      Kd in the micromolar range. Here we present the three-dimensional solution
      structure of a 36-nucleotide ATP-binding RNA aptamer complexed with AMP,
      determined from NMR-derived distance and dihedral angle restraints. The conserved
      loop and bulged G form a novel compact, folded structure around the AMP. The
      backbone tracing of the loop nucleotides can be described by a Greek zeta (zeta).
      Consecutive loop nucleotides G, A, A form a U-turn at the bottom of the zeta, and
      interact with the AMP to form a structure similar to a GNRA tetraloop, with AMP
      standing in for the final A. Two asymmetric G. G base pairs close the stems
      flanking the internal loop. Mutated aptamers support the existence of the
      tertiary interactions within the consensus nucleotides and with the AMP found in
      the calculated structures.

PMID- 8756407
TI  - The intranuclear site of excision of each intron in Balbiani ring 3 pre-mRNA is
      influenced by the time remaining to transcription termination and different
      excision efficiencies for the various introns.
AB  - The 10.9-kb Balbiani ring 3 (BR3) gene contains 38 constitutively excised
      introns. Both nascent and nucleoplasmic, released BR3 gene pre-mRNA can be
      isolated by microdissection of the polytene salivary gland nuclei in which the
      gene is transcribed. Here we analyze the order of intron excision in relation to
      transcription and to intranuclear transport. We demonstrate that the introns are
      excised with an overall 5' to 3' polarity that is established during
      transcription and maintained during transport. In contrast, we also show that
      individual introns are excised at very different rates and that neighboring
      introns are removed in a preferred order that is not necessarily 5' to 3'.
      Splicing factors are, in addition, shown to associate with the nascent BR3 pre
      mRNA. Our data argue that functional spliceosomes assemble rapidly as introns
      appear in the pre-mRNA, but that intron-specific properties influence the
      kinetics of spliceosome assembly and/or function, resulting in cotranscriptional
      excision of some introns, preferentially those located in the 5' part of the pre
      mRNA, and posttranscriptional excision of other introns, preferentially those
      located in the 3' part of the pre-mRNA.

PMID- 8756408
TI  - A chloroplast transcript lacking the 3' inverted repeat is degraded by 3'-->5'
      exoribonuclease activity.
AB  - Chlamydomonas reinhardtii strains harboring deletions of the chloroplast atpB 3'
      inverted repeat (IR) are weakly phototrophic due to reduced accumulation of
      discrete atpB transcripts and the chloroplast ATPase beta-subunit protein. A
      sequence of 18 guanosine residues, which can impede a 3'-->5' exoribonuclease in
      vitro, is able to substitute for the atpB IR in vivo. Strains containing the poly
      guanosine tract in place of the atpB 3' IR are phototrophic and accumulate near
      wild-type levels of discrete atpB transcripts and the ATPase beta-subunit
      protein. Because these atpB transcripts contain the 18 guanosine residues, and
      the poly-guanosine tract is not a terminator of transcription, the accumulation
      of discrete atpB transcripts is likely the result of impediment of 3'-->5'
      exoribonuclease activity. These findings support a model in which atpB
      transcripts lacking the 3' IR are degraded by 3'-->5' exoribonuclease activity,
      and demonstrate that the poly-guanosine tract can be used to study chloroplast
      RNA metabolism in vivo.

PMID- 8756409
TI  - Cis-acting elements distinct from the 5' splice site promote U1-independent pre
      mRNA splicing.
AB  - We have identified a class of pre-mRNAs that are spliced in HeLa extracts
      depleted for U1 snRNP (delta U1 extracts). Previously, we described pre-mRNAs
      that can be spliced in delta U1 extracts only when high concentrations of SR
      splicing factors are added. In contrast, the substrates characterized here are
      efficiently processed in delta U1 extracts without the addition of excess SR
      proteins. The members of this class comprise both a naturally occurring pre-mRNA,
      from the Drosophila fushi tarazu gene, and a chimera containing sequences from
      two different pre-mRNAs that individually are dependent upon U1 snRNP or excess
      SR proteins. Several sequence elements account for the variations in dependence
      on U1 snRNP and SR proteins for splicing. In one pre-mRNA, a single element was
      identified adjacent to the branch site. In the other, two elements flanking the
      5' splice site were found to be critical. This U1-independent splicing reaction
      may provide a mechanism for cells to control the extent of processing of
      different classes of pre-mRNAs in response to altered activities of SR proteins,
      and furthermore suggests that U1 snRNP-independent splicing may not be uncommon.

PMID- 8756410
TI  - Differences in the interaction of Escherichia coli RNase P RNA with tRNAs
      containing a short or a long extra arm.
AB  - The phosphorothioate footprinting technique was applied to the investigation of
      phosphate moieties in tRNA substrates involved in interactions with M1 RNA, the
      catalytic subunit of Escherichia coli RNase P. In general agreement with previous
      data, all affected sites were localized in acceptor stem and T arm. But the
      analyzed examples for class I (Saccharomyces cerevisiae pre-tRNA(Phe) with short
      variable arm) and class II tRNAs (E. coli pre-tRNA(Tyr) with large variable arm)
      revealed substantial differences. In the complex with pre-tRNA(Phe), protection
      was observed at U55, C56, and G57, along the top of the T loop in the tertiary
      structure, whereas in pre-tRNA(Tyr), the protected positions were G57, A58, and
      A59, at the bottom of the T loop. These differences suggest that the size of the
      variable arm affects the spatial arrangement of the T arm, providing a possible
      explanation for the discrepancy in reports about the D arm requirement in
      truncated tRNA substrates for eukaryotic RNase P enzymes. Enhanced reactivities
      were found near the junction of acceptor and T stem (U6, 7, 8 in pre-tRNA(Phe)
      and G7, U63, U64 in pre-tRNA(Tyr)). This indicates a partial unfolding of the
      tRNA structure upon complex formation with RNase P RNA.

PMID- 8756411
TI  - Essential nucleotides direct neuron-specific splicing of gamma 2 pre-mRNA.
AB  - Tissue-and stage-specific pre-mRNA splicing events are prevalent in mammals, yet
      molecular details are lacking about these important mechanisms of
      posttranscriptional gene control. In this study, we investigate the regulated
      splicing of rat gamma 2 pre-mRNA, a subunit of the GABAA receptor, as a step
      toward understanding the molecular basis of a neuron-specific splicing event
      involving cassette exon selection. Cell-and substrate-specific regulation of
      gamma 2 pre-mRNA is recapitulated in a neuronal cell line derived from the
      cerebellum, which produces enhanced levels of the exon-selected mRNA. In
      contrast, a control cell line derived from non-neuronal cells of the pituitary
      produces prominent levels of the unregulated, exon-skipped mRNA. The cerebellar
      and pituitary cell lines are well matched in overall splicing efficiency and
      produce an invariant pattern of splicing for a control substrate, which is
      alternatively spliced but not regulated in this system. The appropriateness of
      the two cell lines is indicated by an extended mRNA mapping experiment, which
      documents the region-specific switch in exon selection throughout rat brain.
      Using this pair of cell lines, we show that large intron segments flanking the
      regulated exon are dispensable for regulation. These intron regions have been
      deleted to generate a minimal splicing substrate for the purpose of identifying
      essential RNA elements. In this context, we show that essential nucleotides are
      located at positions +7, +8, and +9 of the regulated exon and in a 9-nt adenosine
      rich region of the adjacent 3' splice site. Due to the proximity and base
      complementarity of the required nucleotides, experiments were devised to test
      models involving the recognition of two single-stranded signals, or one duplex
      RNA signal. These results clearly disfavor the duplex RNA recognition model and
      indicate that the required regions are recognized as independent, single strands
      in neuronal cells. A weak 5' splice site adjacent to the regulated exon is
      required as a third essential element. Although the importance of a weak 5'
      splice site is common to other regulated systems such as NCAM, the essential
      nucleotides in the exon and 3' splice site region defined in this study for gamma
      2 splicing regulation are novel.

PMID- 8756412
TI  - Novel requirements in peripheral structures of the extended satellite 2
      hammerhead.
AB  - A number of RNAs that infect plants self-cleave using a domain called the
      hammerhead. The consensus plant hammerhead has three base paired stem structures.
      Stems I and III flank the cleaved phosphodiester and are connected to stem II by
      two unpaired and highly conserved sequences. We demonstrated previously that
      satellite 2 transcripts from the newt, Notophthalmus viridescens, use a modified
      hammerhead structure for self-cleavage. Here we show that hammerheads with
      similar modifications occur in satellite 2 from species representing two
      additional families of salamanders (Ambystoma talpoideum and Amphiuma
      tridactylum). The distinctive features of the modified satellite 2 hammerheads
      include unusually short stem III regions and internally looped extensions to stem
      I that are required for cleavage. However, despite the strict nucleotide
      requirement in the internal stem I loop of the newt hammerhead, the details of
      the stem I extensions differ in the three salamanders. An analysis of chimeric
      transcripts indicated that, in order for a specific stem I extension to be
      functional, it must be compatible with other regions of the modified satellite 2
      hammerhead. One such region is stem II, and a mutational analysis has confirmed
      that there are specific sequence and/or structural requirements in stem II.

PMID- 8756413
TI  - Requirement for SLU7 in yeast pre-mRNA splicing is dictated by the distance
      between the branchpoint and the 3' splice site.
AB  - Yeast pre-mRNA splicing factors SLU7 and PRP16 are required for cleavage of the
      3' splice site and exon ligation in vitro. Using natural and model precursor
      RNAs, we found that SLU7 is dispensable for splicing of RNAs in which the 3'
      splice site is in close proximity to the branchpoint. SLU7 is only required when
      the interval between the branchpoint and the 3' splice site is greater than 7 nt.
      In contrast, PRP16 is essential for splicing of all pre-mRNAs tested.
      Immunoprecipitation of the products of step 1 by anti-SLU7 antibodies
      demonstrates that SLU7 is a component of the spliceosome. Recruitment of SLU7 to
      the spliceosome is greatly enhanced by prior addition of PRP16. PRP16 is
      liberated from the spliceosome after completion of step 2, whereas SLU7 remains
      bound to the excised intron and spliced mature RNA until the spliceosome
      disassembles, in a reaction that requires ATP.

PMID- 8756414
TI  - Kinetic pathway for folding of the Tetrahymena ribozyme revealed by three UV
      inducible crosslinks.
AB  - The kinetics of RNA folding were examined in the L-21 ribozyme, an RNA enzyme
      derived from the self-splicing Tetrahymena intron. Three UV-inducible crosslinks
      were mapped, characterized, and used as indicators for the folded state of the
      ribozyme. Together these data suggest that final structures are adopted first by
      the P4-P6 independently folding domain and only later in a region that positions
      the P1 helix (including the 5' splice site), a region whose folding is linked to
      that of a portion of the catalytic core. At intermediate times, a non-native
      structure forms in the region of the triple helical scaffold, which connects the
      major folding domains. At 30 degrees C, the unfolded ribozyme passes through
      these stages with a half-life of 2 min from the time magnesium cations are
      provided. At higher temperatures, the half-life is shortened but the order of
      events is unchanged. Thermal melting of the fully folded ribozyme also revealed a
      multi-stage process in which the steps of folding are reversed: the kinetically
      slowest structure is the least stable and melts first. These structures of the
      ribozyme also bind Mg2+ cooperatively and their relative affinity for binding
      seems to be a major determinant in the order of events during folding. Na+ can
      also substitute for Mg2+ to give rise to the same crosslinkable structures, but
      only at much higher concentrations. Specific binding sites for Mg2+ may make this
      cation particularly efficient at electrostatic stabilization during folding of
      these ribozyme structures.

PMID- 8756415
TI  - Dopaminergic regulation of progesterone receptors: brain D5 dopamine receptors
      mediate induction of lordosis by D1-like agonists in rats.
AB  - To characterize the signaling pathway by which the neurotransmitter dopamine
      modulates progesterone receptor (PR) activation, the steroid-dependent behavior
      lordosis was used in estrogen-primed ovariectomized Sprague-Dawley rats with
      stereotaxic implanted third ventricle cannulas. Lordosis was observed in response
      to solicitous males in females after central administration of the D1-like
      agonist SKF38393 and three of its analogs (SKF77434, SKF75640, and SKF85174). In
      contrast, D1-like antagonist SCH23390 and D1-like/D2 repopulation inhibitor EEDQ
      blocked behavior inducible by the D1-like agonists. Further, antisense
      oligonucleotides to D5, but not D1, dopamine receptor mRNA suppressed
      reproductive behavior associated with D1-like stimulation. This finding provides
      strong evidence that dopaminergic modulation of lordosis is mediated by the novel
      D5 dopamine receptor. Although D1, but not D5, dopamine receptor mRNAs were
      detected in the ventromedial nucleus (VMN) by in situ hybridization, agonists
      microinjected into the VMN, but not into the arcuate nucleus or preoptic area,
      induced lordosis, suggesting the functional presence of D5 dopamine receptors in
      the VMN. Also in support, D5 receptor mRNA antisense microinjected into the VMN
      blocked the subsequent induction of lordosis by D1-like agonists. Finally,
      facilitation of sex behavior by D1-like agonists was blocked by the antiprogestin
      RU38486 and PR antisense oligonucleotide. Collectively, the data provide strong
      evidence for dopaminergic modulation of reproductive behavior through D5 dopamine
      receptor-mediated modulation of PR-dependent behavior in rat CNS.

PMID- 8756416
TI  - Characterization of functional GABAergic synapses formed between rat hypothalamic
      neurons and pituitary intermediate lobe cells in coculture: Ca2+ dependence of
      spontaneous IPSCs.
AB  - Rat hypothalamic neurons and endocrine cells from the intermediate lobe of the
      pituitary were grown in dissociated coculture. Neurons positively stained with an
      antibody against glutamate decarboxylase established apparent contacts with the
      alpha-melanocyte-stimulating hormone-positive endocrine cells. These sites of
      contact were intensely labeled with an antibody against the synaptic protein
      synapsin I and displayed ultrastructural features characteristic of synapses.
      Using patch-clamp recordings, we have demonstrated that these contacts correspond
      to functional GABAergic synapses. The synaptic currents were blocked reversibly
      by bicuculline (5 microM) and SR95531 (5 microM), two competitive antagonists of
      the GABAA receptor. At a holding potential of -60 mV, spontaneously occurring
      IPSCs (s-IPSCs) had small amplitudes (10-100 pA), whereas electrically evoked
      IPSCs (ee-IPSCs) had amplitudes up to 1 nA. The rise times of both types of IPSCs
      were fast ( < or = 1 msec), and their decaying phases were fitted in most cases
      with a single exponential function (time constant 50 msec). The amplitude
      distribution of s-IPSCs did not reveal clear, equally spaced peaks and was little
      affected by tetrodotoxin, suggesting that most s-IPSCs were miniature IPSCs.
      Reduction of extracellular calcium concentration to 0.3 mM induced a marked
      decrease in s-IPSC frequency and revealed a single amplitude peak at 10 pA,
      suggesting that a single quantum of GABA activates 8-10 GABAA channels. Thus, our
      preparation might be an interesting model to study different aspects of synapse
      formation between a central neuron and its target as well as the fundamental
      mechanisms of synaptic transmission at central synapses.

PMID- 8756417
TI  - Voltage-gated K+ channel beta subunits: expression and distribution of Kv beta 1
      and Kv beta 2 in adult rat brain.
AB  - Recent cloning of K+ channel beta subunits revealed that these cytoplasmic
      polypeptides can dramatically alter the kinetics of current inactivation and
      promote efficient glycosylation and surface expression of the channel-forming
      alpha subunits. Here, we examined the expression, distribution, and association
      of two of these beta subunits, Kv beta 1 and Kv beta 2, in adult rat brain. In
      situ hybridization using cRNA probes revealed that these beta-subunit genes are
      heterogeneously expressed, with high densities of Kv beta 1 mRNA in the striatum,
      CA1 subfield of the hippocampus, and cerebellar Purkinje cells, and high
      densities of Kv beta 2 mRNA in the cerebral cortex, cerebellum, and brainstem.
      Immunohistochemical staining using subunit-specific monoclonal and affinity
      purified polyclonal antibodies revealed that the Kv beta 1 and Kv beta 2
      polypeptides frequently co-localize and are concentrated in neuronal perikarya,
      dendrites, and terminal fields, and in the juxtaparanodal region of myelinated
      axons. Immunoblot and reciprocal co-immunoprecipitation analyses indicated that
      Kv beta 2 is the major beta subunit present in rat brain membranes, and that most
      K+ channel complexes containing Kv beta 1 also contain Kv beta 2. Taken together,
      these data suggest that Kv beta 2 is a component of almost all K+ channel
      complexes containing Kv 1 alpha subunits, and that individual channels may
      contain two or more biochemically and functionally distinct beta-subunit
      polypeptides.

PMID- 8756418
TI  - Changes in the electrical properties of supraoptic nucleus oxytocin and
      vasopressin neurons during lactation.
AB  - Magnocellular oxytocin (OT) and vasopressin (VP) neurons adopt different firing
      patterns in response to relevant physiological stimuli. OT neurons selectively
      display short (2-4 sec), high-frequency bursts of action potentials that are
      highly synchronized and correlated with OT release during lactation. The present
      experiments were done to determine whether the electrophysiological properties of
      OT neurons differ from those of VP neurons, and whether these properties are
      modulated during lactation to support short bursting activity. Intracellular
      recordings in vitro were obtained from immunochemically identified supraoptic
      neurons of diestrous or lactating female rats. Resting membrane potential, input
      resistance, membrane time constant, and the depolarizing afterpotential did not
      differ among groups. However, near spike threshold, OT, but not VP, neurons
      expressed a sustained outward rectification that was removed by small
      hyperpolarizing pulses and a rebound depolarization that occurred at the offset
      of these hyperpolarizing pulses. The rebound depolarization was short ( < 2 sec),
      supported brief bursts of action potentials, and was significantly larger during
      lactation. Neurons expressing the outward rectification also exhibited strong
      spike frequency adaptation during prolonged (1-4 sec) depolarization. Spike
      width, the Ca(2+)- dependent afterhyperpolarization, and the degree of spike
      broadening of OT, but not VP, neurons were also larger during lactation,
      suggesting an increase in Ca2+ influx per spike. The results indicate that OT
      neurons possess properties favoring the expression of short spike trains, and
      that some of these properties are enhanced during lactation. In addition, spikes
      in OT neurons may promote more Ca2+ influx in this state.

PMID- 8756419
TI  - Plasticity in GABAA receptor subunit mRNA expression by hypothalamic
      magnocellular neurons in the adult rat.
AB  - The magnocellular hypothalamic neurons exhibit a substantial degree of structural
      and functional plasticity over the time of pregnancy, parturition, and lactation.
      This study has used in situ hybridization techniques to examine whether the
      content of alpha 1, alpha 2, beta 2, gamma 2 GABAA receptor subunit mRNAs
      expressed by these cells fluctuates over this period. A process of regional,
      followed by cellular and then topographical, analyses within the supraoptic (SON)
      and posterior paraventricular (PVN) nuclei revealed that an increase in
      magnocellular alpha 1 subunit mRNA content occurred during the course of
      pregnancy up to day 19, after which a decline in expression was detected on the
      day of parturition. Significant fluctuations of this nature were observed only in
      the oxytocin neuron-enriched regions of the SON and PVN. The expression of alpha
      2, beta 2, and gamma 2 subunit mRNAs in the SON and PVN and of all subunit mRNAs
      in the cingulate cortex did not change over this period. During lactation, gamma
      2 subunit mRNA content within the PVN increased significantly on day 14 of
      lactation as compared with day 7, and topographical analysis suggested that it
      involved principally magnocellular vasopressin neurons. These results demonstrate
      the cell-and subunit-specific regulation of GABAA receptor mRNA expression within
      the hypothalamic magnocellular system. In particular, they suggest that
      fluctuations in alpha 1 subunit expression may contribute to the marked
      variations in electrical activity exhibited by magnocellular oxytocin neurons at
      the time of parturition. More generally, they provide evidence in support of
      GABAA receptor plasticity within a physiological context in the adult rat brain.

PMID- 8756421
TI  - Multiple components of Ca2+ channel facilitation in cerebellar granule cells:
      expression of facilitation during development in culture.
AB  - The contribution of pharmacologically distinct Ca2+ channels to prepulse-induced
      facilitation was studied in mouse cerebellar granule cells. Ca2+ channel
      facilitation was measured as the percentage increase in the whole-cell current
      recorded during a test pulse before and after it was paired with a positive
      prepulse. The amount of facilitation was small in recordings made during the
      first few days in tissue culture but increased substantially after 1 week. L-type
      channels accounted for the largest proportion of facilitation in 1-week-old cells
      (60-70%), whereas N-type channels contributed very little (approximately 3%). The
      toxins omega-agatoxin IVa or omega-conotoxin MVIIC (after block of N-, L-, and P
      type channels) each blocked a small percentage of facilitation (approximately 12
      and 14%, respectively). Perfusion of cells with GTP-gamma-S enhanced the
      facilitation of N-type channels, whereas it inhibited of L-type channels. During
      development in vitro, the contribution of L-type channels to the whole-cell
      current decreased. Single-channel recordings showed the presence of 10 and 15 pS
      L-type Ca2+ channels in 1-d-old cells. After 1 week in culture, a approximately
      25 pS L-type channel dominated recordings from cell-attached patches. Positive
      prepulses increased the activity of the 25 pS channel but not of the smaller
      conductance channels. The expression of Ca(2+) channel facilitation during
      development may contribute to changes in excitability that allow frequency
      dependent Ca(2+) influx during the period of active synaptogenesis

PMID- 8756420
TI  - Effects of salicylate and lanthanides on outer hair cell motility and associated
      gating charge.
AB  - Salicylate, one of the most widely used drugs, is known to induce reversible
      tinnitus and hearing loss. Salicylate interferes with outer hair cells (OHCs),
      which are believed to underlie normal auditory frequency selectivity and
      sensitivity. In the present experiments, the effects of salicylate and
      lanthanides on OHC motility and nonlinear capacitance were investigated by using
      isolated guinea-pig OHCs while attempting to avoid inadvertent intracellular
      pressure change, which itself can affect OHC motility and capacitance. Either
      extracellularly or intracellularly applied salicylate reduced nonlinear peak
      capacitance (Cmpk) and shifted the voltage at peak capacitance to depolarized
      levels. Concentration-response curves for reduction in Cmpk by salicylate and
      GdCl3 revealed a half-maximal concentration and Hill coefficient of 1.6 mM and
      1.0, and 0.6 mM and 1.2, respectively. In comparable groups of OHCs, the normal
      Cmpk values of which were near 40 pF, average Cmpk decreased to 28 and 36 pF for
      intracellularly and extracellularly applied salicylate, respectively. Salicylate
      reduced, but did not completely block, the voltage-induced length change.
      Extracellularly, but not intracellularly, applied lanthanide blocked voltage
      induced movement and capacitance almost completely. After intracellular trypsin
      treatment, salicylate reduced voltage-dependent capacitance reversibly,
      suggesting that salicylate directly acts on the sensor/motor and not via effects
      on intracellular structures, such as the subsurface cisternae. The results are
      consistent with the hypothesis that the dissociated, charged form of salicylate
      directly interacts with the sensor/motor on the inner aspect of the OHC plasma,
      whereas lanthanides interact on the outer aspect.

PMID- 8756422
TI  - Reduction of calcium currents by Lambert-Eaton syndrome sera: motoneurons are
      preferentially affected, and L-type currents are spared.
AB  - Previous work has demonstrated that Lambert-Eaton syndrome (LES) antibodies
      reduce calcium currents in nonneuronal cells and neurons and reduce the amplitude
      of extracellularly recorded currents at mouse motor nerve terminals. We compared
      effects of LES sera on whole-cell currents of cultured nerve and muscle. LES sera
      more strongly reduced calcium currents in motoneurons than in sensory neurons.
      Motoneuronal potassium currents were unaffected. The sera minimally affected
      calcium currents in skeletal and cardiac muscle. In motoneurons, both low voltage
      activated (LVA) and high voltage-activated (HVA) components of calcium current
      were decreased, demonstrating that the sera targeted more than one calcium
      channel type. The HVA current remaining in LES-treated motoneurons was little
      affected by micromolar omega-conotoxin MVIIC but was reduced > 70% by micromolar
      nimodipine. This pharmacological profile contrasts with untreated cells and
      suggest that LES sera primarily spare L-type currents in motoneurons.

PMID- 8756423
TI  - The clustering of axonal sodium channels during development of the peripheral
      nervous system.
AB  - The distribution of Na+ channels in rat peripheral nerve was measured during
      development by using immunofluorescence. Small segments of sciatic nerve from
      postnatal day 0-13 (P0-P13) pups were labeled with an antibody raised against a
      well conserved region of the vertebrate Na+ channel. At day P0 axons contained
      almost no Na+ channel aggregates. The number of clusters increased dramatically
      throughout the first week. In almost all cases Na+ channels clustered in the
      vicinity of Schwann cell processes. At least four classes of aggregates were
      noted. Clusters formed singly at Schwann cell edges, in pairs or in broad regions
      between neighboring Schwann cells, and in more focal zones at presumptive nodes.
      Almost all Na+ channel aggregates had reached the latter stage by the end of the
      first week. Histograms plotting the frequency of occurrence of each cluster type
      suggested a sequence of events in node formation involving the initiation of
      channel aggregation by Schwann cell processes. The requirement for Schwann cells
      during sodium channel clustering was tested by blocking proliferation of these
      cells with the antimitotic agent mitomycin C. Na+ channel clustering was sharply
      reduced, whereas node formation was normal at a distal site along the same nerve.
      Immunocytochemical detection of myelin-associated glycoprotein (MAG) indicated
      that Schwann cells must begin to ensheathe axons before inducing Na+ channel
      clustering.

PMID- 8756424
TI  - Site specificity of short-term and long-term habituation in the tail-elicited
      siphon withdrawal reflex of Aplysia.
AB  - The study of habituation in animals with relatively simple nervous systems has
      contributed significantly to the understanding of mechanisms underlying learning
      and memory. Using the tail-elicited siphon withdrawal reflex of Aplysia, which is
      mediated in part by bilaterally symmetrical clusters of tail sensory neurons, we
      found that both short-term and long-term habituation can be restricted laterally,
      such that habituation produced by stimulation of one side of the tail does not
      generalize to the other side. Further experiments in this preparation revealed
      that long-term, laterally restricted habituation is sensitive to the temporal
      pattern with which stimuli are presented. We also determined that both short-term
      and long-term habituation can take place in a reduced behavioral preparation, and
      that short-term habituation can be restricted within relatively small stimulation
      sites located on the same side of the tail. These results provide insights into
      the cellular organization of habituation, and they provide a useful preparation
      for a cellular analysis of this basic form of learning.

PMID- 8756425
TI  - Heterosynaptic facilitation of tail sensory neuron synaptic transmission during
      habituation in tail-induced tail and siphon withdrawal reflexes of Aplysia.
AB  - In cellular studies of habituation, such as in the gill and siphon withdrawal
      reflex to tactile stimulation of the siphon of Aplysia, a mechanism that has
      emerged as an explanation for response decrement during habituation is
      homosynaptic depression at sensory neurons mediating the behavioral response. We
      have examined the contribution of homosynaptic depression to habituation in
      sensory neurons that contribute to two reflex behaviors in Aplysia, tail
      withdrawal and siphon withdrawal, both elicited by threshold-level tail
      stimulation. In a companion paper (this issue), we reported that repeated tail
      stimulation, identical to that producing habituation in siphon withdrawal in
      freely moving animals, also produces habituation in reduced preparations. In this
      paper, we extend these behavioral findings by showing that in reduced
      preparations, identical tail stimulation also produces habituation of the tail
      withdrawal reflex. In addition, our cellular experiments show that (1) identified
      sensory and motor neurons in both reflex systems respond to identical repeated
      tail stimulation; in sensory neurons it produces a progressive decrease in spike
      number and increase in spike latency, and in motor neurons it produces
      progressive decrement in complex EPSPs and spike output. (2) Homosynaptic
      depression of the tail sensory neuron to tail motor neuron synapse does occur
      when the sensory neurons are activated repetitively by intracellular current. (3)
      Homosynaptic depression at this synapse does not occur when the sensory neurons
      are activated repetitively by threshold-level tail stimuli that elicit the
      behavioral reflex and cause habituation; rather, the sensory neurons exhibit
      significant heterosynaptic facilitation. Thus, in these reflexes, habituation is
      not accompanied by homosynaptic depression at the sensory neurons, suggesting
      that the plasticity underlying habituation occurs primarily at interneuronal
      sites.

PMID- 8756426
TI  - Myomodulin gene of Lymnaea: structure, expression, and analysis of neuropeptides.
AB  - The myomodulin family of neuropeptides is an important group of neural
      cotransmitters in molluscs and is known to be present in the neural network that
      controls feeding behavior in the snail Lymnaea. Here we show that a single gene
      encodes five structurally similar forms of myomodulin: GLQMLRLamide,
      QIPMLRLamide, SMSMLRLamide, SLSMLRLamide, and PMSMLRLamide, the latter being
      present in nine copies. Analysis of the organization of the gene indicates that
      it is transcribed as a single spliced transcript from an upstream promoter region
      that contains multiple cAMP-responsive elements, as well as putative elements
      with homology to tissue-specific promoter-binding sites. The presence in nervous
      tissue of two of the peptides, GLQMLRLamide and PMSMLRLamide, is confirmed by
      mass spectrometry. In situ hybridization analysis indicates that the gene is
      expressed in specific cells in all ganglia of the CNS of Lymnaea, which will
      allow physiological analysis of the function of myomodulins at the level of
      single identified neurons.

PMID- 8756427
TI  - Activation of intrinsic and synaptic currents in leech heart interneurons by
      realistic waveforms.
AB  - Leech heart interneurons were voltage-clamped with realistic waveforms to
      investigate the currents underlying the oscillation in the cells. By estimating
      the leak current parameters in regions in which there was little contamination by
      voltage-gated currents, it was possible to measure the Ca2+ current, the
      persistent Na+ current, Ip, and the hyperpolarization-activated inward current,
      Ih. The experiments verified a prediction of a computer model of HN cells that
      the shape of the typical waveform was such that the low-threshold Ca2+ currents
      were partially inactivated during a slow up-ramp to a plateau potential. A step
      within the same range of the membrane potential as the realistic waveform
      produced > 4 times as much Ca2+ current. In two-cell voltage-clamp experiments,
      the step produced 20 times more graded inhibition than the normal presynaptic
      waveform. When the presynaptic heart interneuron oscillated with spikes, the
      graded inhibition was larger. The difference may arise from integration of a
      slowly decaying component of the spike-mediated inhibition. The persistent Na+
      current had a very low threshold. During the most hyperpolarized phase of the
      waveform, Ip deactivated to 50% of its maximum conductance. A substantial part of
      Ip, therefore, was effectively contributing to the leak current in the HN cells.
      The h-current increased for waveforms that had longer periods, whereas increasing
      the h-current in the model reduced the period. The h-current thus provides
      negative feedback to perturbations that alter the period of the oscillation.

PMID- 8756428
TI  - Multiple actions of 1S,3R-ACPD in modulating endogenous synaptic transmission to
      spinal respiratory motoneurons.
AB  - To determine physiological roles of metabotropic glutamate receptors (mGluRs)
      affecting breathing, we examined the effects of (1S,3R)-1-aminocyclopentane-1,3
      dicarboxylic acid (1S,3R-ACPD) on synaptic transmission and excitability of
      phrenic motoneurons (PMNs) in an in vitro neonatal rat brainstem/spinal cord
      preparation. The effects of 1S,3R-ACPD were multiple, including reduction of
      inspiratory-modulated synaptic currents and increase of neuronal excitability via
      an inward current (Iacpd) associated with a decrease of membrane conductance. The
      mechanism underlying synaptic depression was examined. We found that 1S,3R-ACPD
      reduced the frequency but not the amplitude of miniature excitatory postsynaptic
      currents. The current induced by exogenous AMPA was not significantly affected by
      1S,3R-ACPD. These results suggest that 1S,3R-ACPD-induced reduction of
      inspiratory synaptic currents is mediated by presynaptic mGluRs. We also examined
      the ionic basis for Iacpd. We found that Iacpd had a reversal potential of
      approximately -100 mV, close to the estimated, EK+ (-95 mV). Elevating
      extracellular [K+] to 9 mM reduced the Iacpd reversal potential to -75 mV. The K+
      channel blocker Ba2+ induced an inward current with a reversal potential at -93
      mV associated with a decrease of membrane conductance, closely resembling the
      effect of 1S,3R-ACPD. Moreover, Ba2+, occluded 1S,3R-ACPD effects. In the
      presence of Ba2+, Iacpd and the 1S,3R-ACPD-induced decrease of membrane
      conductance were diminished. Our data indicate that the dominant component of
      Iacpd results from the blockade of a Ba(2+)-sensitive resting K+ conductance. We
      conclude that the activation of mGluRs affects the inspiratory-modulated activity
      of PMNs via distinct mechanisms at pre- and postsynaptic sites.

PMID- 8756429
TI  - The alpha 1E calcium channel exhibits permeation properties similar to low
      voltage-activated calcium channels.
AB  - The physiological and pharmacological properties of the alpha 1E calcium (Ca)
      channel subtype do not exactly match any of the established categories described
      for native neuronal Ca currents. Many of the key diagnostic features used to
      assign cloned Ca channels to their native counterparts, however, are dependent on
      a number of factors, including cellular environment, beta subunit coexpression,
      and modulation by second messengers and G-proteins. Here, by examining the
      intrinsic pore characteristics of a family of transiently expressed neuronal Ca
      channels, we demonstrate that the permeation properties of alpha 1E closely
      resemble those described for a subset of low-threshold Ca channels. The alpha 1A
      (P-/Q-type), alpha 1B (N-type), and alpha 1C (L-type) high-threshold Ca channels
      all exhibit larger whole-cell currents with barium (Ba) as the charge carrier as
      compared with Ca or strontium (Sr). In contrast, macroscopic alpha 1E currents
      are largest in Sr, followed by Ca and then Ba. The unique permeation properties
      of alpha 1E are maintained at the single-channel level, are independent of the
      nature of the expression system, and are not affected by coexpression of alpha 2
      and beta subunits. Overall, the permeation characteristics of alpha 1E are
      distinct from those described for R-type currents and share some similarities
      with native low-threshold Ca channels.

PMID- 8756430
TI  - Neural influence on protein kinase C isoform expression in skeletal muscle.
AB  - Protein kinase C (PKC) is a family of enzymes involved in synapse formation and
      signal transduction at the neuromuscular junction. Two PKC isoforms, classical
      PKC alpha and novel PKC theta, have been shown to be enriched in skeletal muscle
      or localized to the endplate. We examined the role of nerve in regulating the
      expression of these PKC isoforms in rat skeletal muscle by denervating diaphragm
      muscle and measuring PKC protein expression at various postoperative times. nPKC
      theta protein levels decreased 65% after denervation, whereas cPKC alpha levels
      increased 80% compared with control hemidiaphragms. These results suggest that
      innervation regulates PKC theta and alpha isoform expression in skeletal muscle.
      To explore further how nerve regulates PKC expression, we characterized PKC
      isoform expression in rat myotubes deprived of neural input. Myoblast expression
      of nPKC theta was low, and the increase in nPKC theta expression that occurred
      during differentiation into myotubes resulted in levels of nPKC theta
      significantly below adult skeletal muscle. cPKC alpha expression in myoblastic
      increased during differentiation to levels that exceeded expression in adult
      skeletal muscle. Coculturing myotubes within neuroblastoma X glioma hybrid clonal
      cell line (NG108-15) increased nPKC theta expression, but not cPKC alpha,
      suggesting that nPKC theta in skeletal muscle and myotubes is regulated by nerve
      contact or by a factor(s) provided by nerve. Treating myotubes with tetrodotoxin
      did not affect either basal- or NG108-15 cell-stimulated nPKC theta expression.
      Together these results suggest that expression of nPKC theta in skeletal muscle
      is regulated by a transynaptic interaction with nerve that specifically
      influences nPKC theta expression.

PMID- 8756431
TI  - Vicious cycle involving Na+ channels, glutamate release, and NMDA receptors
      mediates delayed neurodegeneration through nitric oxide formation.
AB  - The mechanisms by which neurons die after cerebral ischemia and related
      conditions in vivo are unclear, but they are thought to involve voltage-dependent
      Na+ channels, glutamate receptors, and nitric oxide (NO) formation because
      selective inhibition of each provides neuroprotection. It is not known precisely
      what their roles are, nor whether they interact within a single cascade or in
      parallel pathways. These questions were investigated using an in vitro primary
      cell culture model in which striatal neurons undergo a gradual and delayed
      neurodegeneration after a brief (5 min) challenge with the glutamate receptor
      agonist NMDA. Unexpectedly, NO was generated continuously by the cultures for up
      to 16 hr after the NMDA exposure. Neuronal death followed the same general time
      course except that its start was delayed by approximately 4 hr. Application of
      the NO synthase inhibitor nitroarginine after, but not during, the NMDA exposure
      inhibited NO formation and protected against delayed neuronal death. Blockade of
      NMDA receptors or of voltage-sensitive Na+ channels [with tetrodotoxin (TTX)]
      during the postexposure period also inhibited both NO formation and cell death.
      The NMDA exposure resulted in a selective accumulation of glutamate in the
      culture medium during the period preceding cell death. This glutamate release
      could be inhibited by NMDA antagonism or by TTX, but not by nitroarginine. These
      data suggest that Na+ channels, glutamate receptors, and NO operate
      interdependently and sequentially to cause neurodegeneration. At the core of the
      mechanism is a vicious cycle in which NMDA receptor stimulation causes activation
      of TTX-sensitive Na+ channels, leading to glutamate release and further NMDA
      receptor stimulation. The output of the cycle is an enduring production of NO
      from neuronal sources, and this is responsible for delayed neuronal death. The
      same neurons, however, could be induced to undergo more rapid NMDA receptor
      dependent death that required neither TTX-sensitive Na+ channels nor NO.

PMID- 8756432
TI  - Modification of NMDA receptor channels and synaptic transmission by targeted
      disruption of the NR2C gene.
AB  - A novel strain of mutant mouse has been generated with a deletion of the gene
      encoding the NR2C subunit of the NMDA receptor, which is primarily expressed in
      cerebellar granule cells. Patch-clamp recordings from granule cells in thin
      cerebellar slices were used to assess the consequences of the gene deletion. In
      granule cells of wild-type animals, a wide range of single-channel conductances
      were observed (19-60 pS). The disruption of the NR2C gene results in the
      disappearance of low-conductance NMDA receptor channels ( < 37 pS) normally
      expressed in granule cells during developmental maturation. The NMDA receptor
      mediated synaptic current is markedly potentiated in amplitude, but abbreviated
      in duration (with no net difference in total charge), and the non-NMDA component
      of the synaptic current was reduced. We conclude that the NR2C subunit
      contributes to functional heteromeric NMDA receptor-subunit assemblies at the
      mossy fiber synapse and extrasynaptic sites during maturation, and the
      conductance level exhibited by a given receptor macromolecule may reflect the
      stochiometry of subunit composition.

PMID- 8756433
TI  - Two alternative promoters direct neuron-specific expression of the rat
      microtubule-associated protein 1B gene.
AB  - Microtubule-associated protein 1B (MAP1B) is a major constituent of the neuronal
      cytoskeleton that is expressed at high levels during early brain development and
      plays a role in axonal growth and neuronal plasticity. Previous studies suggested
      that the regulation of its gene expression is primarily at the transcriptional
      level. Thus, the characterization of the promoter region should help to define
      regulatory elements that control neuron-specific and developmental expression of
      the MAP1B gene. We have isolated genomic clones containing up to 11 kb of the
      upstream region of the rat MAP1B gene, sequenced approximately 1.8 kb upstream
      from the translation start codon, and identified several consensus sequences.
      These sequences include a consensus element common to several neuronal genes, a
      TCC repeat, a cAMP response element, and two TATA boxes that were 134 nucleotides
      apart from each other. S1 nuclease and RNase protection assays identified two
      corresponding groups of transcription initiation sites that were used selectively
      in distinct regions of the nervous system and during different stages of
      development. Transient transfection assays with neuronal and non-neuronal cell
      lines demonstrated that each TATA sequence and its corresponding adjacent region
      could independently direct neuron-specific expression of a reporter gene.
      Furthermore, the transcription of the reporter gene was initiated from the same
      sites as those of the MAP1B gene in vivo. These results suggest that two
      alternative and overlapping promoters, one inducible and the other constitutive,
      regulate the temporal and tissue-specific expression of the rat MAP1B gene.

PMID- 8756435
TI  - Distinct properties of neuronal and astrocytic endopeptidase 3.4.24.16: a study
      on differentiation, subcellular distribution, and secretion processes.
AB  - Endopeptidase 3.4.24.16 belongs to the zinc-containing metalloprotease family and
      likely participates in the physiological inactivation of neurotensin. The
      peptidase displays distinct features in pure primary cultured neurons and
      astrocytes. Neuronal maturation leads to a decrease in the proportion of
      endopeptidase 3.4.24.16-bearing neurons and to a concomitant increase in
      endopeptidase 3.4.24.16 activity and mRNA content. By contrast, there is no
      change with time in endopeptidase 3.4.24.16 activity or content in astrocytes.
      Primary cultured neurons exhibit both soluble and membrane-associated
      endopeptidase 3.4.24.16 activity. The latter behaves as an ectopeptidase on
      intact plated neurons and resists treatments with 0.2% digitonin and Na2CO3.
      Further evidence for an association of the enzyme with plasma membranes was
      provided by cryoprotection experiments and electron microscopic analysis. The
      membrane-associated form of endopeptidase 3.4.24.16 increased during neuronal
      differentiation and appears to be mainly responsible for the overall augmentation
      of endopeptidase 3.4.24.16 activity observed during neuronal maturation. Unlike
      neurons, astrocytes only contain soluble endopeptidase 3.4.24.16. Astrocytes
      secrete the enzyme through monensin, brefeldin A, and forskolin-independent
      mechanisms. This indicates that endopeptidase 3.4.24.16 is not released by
      classical regulated or constitutive secreting processes. However, secretion is
      blocked at 4 degrees C and by 8 bromo cAMP and is enhanced at 42 degrees C, two
      properties reminiscent of that of other secreted proteins lacking a classical
      signal peptide. By contrast, neurons appear unable to secrete endopeptidase
      3.4.24.16.

PMID- 8756434
TI  - Ultrastructural evidence for prominent distribution of the mu-opioid receptor at
      extrasynaptic sites on noradrenergic dendrites in the rat nucleus locus
      coeruleus.
AB  - Physiological studies have indicated that agonists at the mu-opioid receptor (mu
      OR), such as morphine or the endogenous peptide methionine5-enkephalin, can
      markedly decrease the spontaneous activity of noradrenergic neurons in the locus
      coeruleus (LC). Messenger RNA and protein for mu OR are also densely expressed by
      LC neurons. During opiate withdrawal, increased discharge rates of LC neurons
      coincide with the expression of behavioral features associated with the opiate
      withdrawal syndrome. To better define the cellular sites for the physiological
      activation of mu OR in the LC and its relation to afferent terminals, we examined
      the ultrastructural localization of mu OR immunoreactivity in sections dually
      labeled for the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH).
      Immunogold-silver labeling for mu OR (i-mu OR) was localized to parasynaptic and
      extrasynaptic portions of the plasma membranes of perikarya and dendrites, many
      of which also contained immunolabeling for TH. The dendrites containing
      exclusively i-mu OR were more numerous in the rostral pole of the LC. The i-mu OR
      in dendrites with and without detectable TH immunoreactivity were usually
      postsynaptic to unlabeled axon terminals containing heterogeneous types of
      synaptic vesicles and forming asymmetric synaptic specializations characteristic
      of excitatory-type synapses. These results provide the first direct
      ultrastructural evidence that mu OR is strategically localized to modulate the
      postsynaptic excitatory responses of catecholamine-containing neurons in the LC.

PMID- 8756436
TI  - Optical recordings of the effects of cholinergic ligands on neurons in the
      ganglion cell layer of mammalian retina.
AB  - Cholinergic regulation of the activity of rabbit retinal ganglion cells and
      displaced amacrine cells was investigated using optical recording of changes in
      intracellular free calcium ([Ca2+]i). Labeling of neurons in the mature retina
      was achieved by injecting calcium green-1 dextran (CaGD) into the isolated
      retina. Nicotine increased ganglion cell [Ca2+]i, affecting every loaded cell in
      some preparations; the pharmacology of nicotine was consistent with an action at
      neuronal nicotinic receptors, and specifically it was kappa-(neuronal
      )bungarotoxin-sensitive but alpha-bungarotoxin-insensitive. Muscarine also raised
      [Ca2+]i, but it was less potent than nicotine, affecting only a subpopulation of
      ganglion cells, with an M1-like muscarinic receptor pharmacology. Neither the
      nicotine- nor muscarine-induced increases of ganglion cell [Ca2+]i were blocked
      by the glutamate receptor antagonists 6,7-dinitroquinoxaline-2,3-dione and
      aminophosphonopentanoic acid. Therefore, the effects of cholinergic agonists on
      ganglion cell [Ca2+]i were not attributable to an indirect effect mediated by
      glutamatergic bipolar cells. The effects of nicotine and muscarine were abolished
      in calcium-free solution, indicating that the responses depend on calcium influx.
      Displaced (Cb) cholinergic amacrine cells were also loaded with CaGD and were
      identified by selective labeling with the nuclear dye 4',6-diamidino-2-phenyl
      indole. Cb amacrine cells did not respond to either nicotine or muscarine, but
      responded vigorously to the glutamate receptor agonist kainic acid. There is
      anatomical evidence indicating that cholinergic amacrine cells make synaptic
      contact with each other, but the present results do not support the hypothesis
      that communication between these cells is cholinergic.

PMID- 8756437
TI  - Hippocampal astrocytes in situ respond to glutamate released from synaptic
      terminals.
AB  - A long-standing question in neurobiology is whether astrocytes respond to the
      neuronal release of neurotransmitters in vivo. To address this question, acutely
      isolated hippocampal slices were loaded with the calcium-sensitive dye Calcium
      Green-1 and the responses of the astrocytes to electrical stimulation of the
      Schaffer collaterals were monitored by confocal microscopy. To confirm that the
      responsive cells were astrocytes, the slices were immunostained for the
      astrocytic marker glial fibrillary acidic protein. Stimulation of the Schaffer
      collaterals (50 Hz, 2 sec) resulted in increases in the concentration of
      intracellular calcium ([Ca2+]i) in the astrocytes located in the stratum radiatum
      of CA1. The astrocytic responses were blocked by the sodium channel blocker
      tetrodotoxin, the voltage-dependent calcium channel blocker omega-conotoxin
      MVIIC, and the selective metabotropic glutamate receptor antagonist alpha-methyl
      4-carboxyphenylglycine (MCPG). These results suggest that the astrocytic
      responses were induced by stimulation of metabotropic glutamate receptors on the
      astrocytes by neuronally released glutamate. The astrocytic responses to neuronal
      stimulation were enhanced in the presence of the K+ channel antagonist 4
      aminopyridine (4-AP). Inhibition of the astrocytic responses in the presence of 4
      AP required the presence of both MCPG and the ionotropic glutamate receptor
      antagonist kynurenic acid. These results suggest that higher levels of neuronal
      activity result in stimulation of both metabotropic and ionotropic glutamate
      receptors on the astrocytes. Overall, the results indicate that hippocampal
      astrocytes in situ are able to respond to the neuronal release of the
      neurotransmitter glutamate with increases in [Ca2+]i.

PMID- 8756438
TI  - Role of Olf-1 and Pax-6 transcription factors in neurodevelopment.
AB  - The Olf-1 transcription factor is expressed in olfactory sensory neurons where it
      regulates the expression of genes that encode components of the odorant signal
      transduction cascade and contributes to the terminal phenotype of these sensory
      neurons. We examined the pattern of expression of Olf-1 protein during mouse
      embryogenesis and observed Olf-1 expression transiently in a subset of neural
      precursor cells in the CNS and peripheral nervous system. The expression of Olf-1
      protein was enriched in sensory components and coincided with postmitotic cells
      and the initiation of overt differentiation within the nervous system. The
      spatial and temporal patterns of Olf-1 expression during development suggest a
      role in neurogenesis that is common among different neural cell types. In
      parallel, the expression pattern of Pax-6, a transcription factor that is widely
      expressed in the developing nervous system, including the visual and olfactory
      systems, was examined with a C-terminal antibody. In the retina, Pax-6 protein is
      detected in the lens, the cornea, and the neural and pigmented retinas. In the
      olfactory epithelium, Pax-6 protein is expressed exclusively in cells of non
      neuronal lineage, including sustentacular cells, basal cells, and Bowman's
      glands. The nonoverlapping, cellular localization patterns of Pax-6 and Olf-1
      demarcate distinct cell lineages within the developing olfactory epithelium.

PMID- 8756440
TI  - Retinal ganglion cell axons recognize specific guidance cues present in the
      deafferented adult rat superior colliculus.
AB  - During development, retinal ganglion cell axons establish a topographically
      ordered projection from the retina to the superior colliculus (SC). The putative
      guidance activities for retinal axons that operate during embryonic development
      are not detectable in the normal adult SC. However, these cues reappear upon
      transection of the optic nerve of adult rats. In the present study, we used a
      modified version of the "stripe assay," in which membranes from either anterior
      or posterior SC alternated with laminin stripes. Temporal embryonic retinal axons
      consistently avoid membranes from embryonic posterior SC, but only rarely from
      adult deafferented SC. However, they are attracted to membranes from both
      embryonic and adult deafferented anterior SC. Nasal retinal axons only show a
      significant preference for membranes from posterior SC after deafferentation.
      When retinal axons were offered a choice to grow on membranes either from their
      embryonic or their deafferented target regions, they showed a preference for the
      deafferented SC. On carpets consisting of laminin and membranes from normal SC
      (not deafferented) or nontarget regions (inferior colliculus), temporal and nasal
      axons grow either in a random fashion or show preferences for the laminin
      stripes. Our modified version of the classic stripe assay shows specific growth
      preferences of embryonic retinal axons for membrane lanes from their appropriate
      embryonic or deafferented adult target regions. These findings suggest that the
      deafferentation of the SC in adult rats triggers the reexpression of specific
      guidance activities for retinal axons. Those "attractive" guidance cues appear to
      be differentially expressed in the developing and deafferented SC.

PMID- 8756439
TI  - Oligodendroglia regulate the regional expansion of axon caliber and local
      accumulation of neurofilaments during development independently of myelin
      formation.
AB  - Axon caliber may be influenced by intrinsic neuronal factors and extrinsic
      factors related to myelination. To understand these extrinsic influences, we
      studied how axon-caliber expansion is related to changes in neurofilament and
      microtubule organization as axons of retinal ganglion cells interact with
      oligodendroglia and become myelinated during normal mouse brain development.
      Caliber expanded and neurofilaments accumulated only along regions of the axon
      invested with oligodendroglia. Very proximal portions of axons within a region of
      the optic nerve from which oligodendrocytes are excluded remained unchanged. More
      distally, these axons rapidly expanded an average of fourfold as soon as they
      were recruited to become myelinated between postnatal days 9 and 120.
      Unmyelinated axons remained unchanged. Axons ensheathed by oligodendroglial
      processes, but not yet myelinated, were intermediate in caliber and neurofilament
      number. That oligodendrocytes can trigger regional caliber expansion in the
      absence of myelin was confirmed using three strains of mice with different
      mutations that prevent myelin formation but allow wrapping of some axons by
      oligodendroglial processes. Unmyelinated axons persistently wrapped by
      oligodendrocytes showed full axon caliber expansion, neurofilament accumulation,
      and appropriately increased lateral spacing between neurofilaments. Thus, signals
      from oligodendrocytes, independent of myelin formation, are sufficient to induce
      full axon radial growth primarily by triggering local accumulation and
      reorganization of the neurofilament network.

PMID- 8756441
TI  - Onset of electrical excitability during a period of circus plasma membrane
      movements in differentiating Xenopus neurons.
AB  - Living neurons are usually first identifiable in primary cultures at the time of
      neurite initiation, and studies of excitability have been restricted largely to
      the subsequent period. A morphological early marker is described that identifies
      neurons for whole-cell voltage-clamp recordings before neurite initiation. Video
      time-lapse recordings of cultured cells dissociated from neurectoderm of Xenopus
      neural plate stage embryos reveal cells demonstrating circus movements, in which
      blebs of plasma membrane propagate around the cell circumference within a period
      of several minutes. All neurons demonstrate circus movements before morphological
      differentiation; the fraction of cells exhibiting circus movements that
      differentiate morphologically depends on the substrate on which they are
      cultured. Blockade of circus activity with cytochalasin B does not prevent
      neuronal differentiation. Circus movements are not neurectoderm-specific because
      they similarly predict differentiation of myocytes developing in mesodermal
      cultures. Initially inexcitable, neurons develop voltage-dependent K+, Na+, and
      Ca2+ currents during the period of several hours in which they exhibit circus
      movements. The early development of depolarization-induced elevations of [Ca2+]i
      several hours before morphological differentiation corresponds to the previously
      described onset of functionally significant spontaneous elevations of [Ca2+]i in
      these neurons and demonstrates a role for early expression of voltage-dependent
      ion channels.

PMID- 8756442
TI  - Precision of reinnervation and synaptic remodeling observed in neuromuscular
      junctions of living frogs.
AB  - Repeated in vivo observations were used to study regenerated nerve terminals in
      neuromuscular junctions of the adult frog Rana pipiens. Sartorius junctions in
      living animals were stained with the fluorescent vital dye RH414 and viewed with
      video fluorescence microscopy. Each junction was observed in the intact muscle
      and then again 7, 10, and 13 weeks after nerve crush. At 13 weeks, junctions were
      determined to be mono- or polyneuronally innervated using intracellular
      recording. Between 7 and 13 weeks, most identified junctions were reinnervated
      less precisely and completely than described previously. Although some of the
      original synaptic gutters were reoccupied by regenerated terminal branches, other
      gutters were only partially occupied, and many appeared abandoned. Junctions
      showing precise recapitulation of original terminal arborizations comprised a
      small number of the total examined, as did those where reinnervation was very
      imprecise. Striking differences in the precision of reinnervation were found
      within the muscle such that distal terminals regenerated more precisely and
      completely than did proximal terminals. Terminals in reinnervated muscles were
      more dynamic than terminals in unoperated muscles over equivalent times. In
      singly innervated junctions, terminal growth was favored over regression. In
      doubly innervated junctions, regressive events were more common. Imprecise
      reinnervation is explained in terms of multisite innervation of muscle fibers and
      the activity dependence of synaptic stability. We hypothesize that when axons
      reinnervate the second or third junctions on a fiber, they do so less precisely,
      because the activity restored by reinnervation of the first junction renders
      later sites less attractive or less stable.

PMID- 8756443
TI  - Actions of substance P on rat neostriatal neurons in vitro.
AB  - Actions of substance P (SP) on the neostriatal neurons in in vitro rat slice
      preparations were studied via whole-cell patch-clamp recording. Almost all large
      aspiny neurons (cholinergic cells) and half of the low-threshold spike (LTS)
      cells (somatostatin/ NOS-positive cells) showed depolarization or an inward shift
      of the holding currents in response to bath-applied SP in a dose-dependent
      manner. In contrast, no responses were observed in fast-spiking (FS) cells
      (parvalbumin-positive cells) and medium spiny cells. Spike discharges followed by
      slow EPSPs/EPSCs were evoked by intrastriatal electrical stimulation in the large
      aspiny neurons. Pretreatment with [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP, an
      antagonist of the SP receptor, reversibly suppressed the induction of the slow
      EPSPs/EPSCs and unmasked slow IPSCs. The SP-induced inward current, although
      almost unchanged even after the blockade of Ih channels and voltage-dependent
      Na+, Ca2+, and K+ channels, changed its amplitude according to the Na+
      concentration used in both the large aspiny neurons and LTS cells. Thus, the
      cation current could account for virtually all of the inward current at resting
      levels in both neurons. These results suggest that the firing of afferent neurons
      such as striatonigral medium spiny neurons, one of the possible sources of SP,
      would increase the firing probability of the two types of interneurons of the
      neostriatum by SP-receptor-mediated opening of tetrodotoxin-insensitive cation
      channels.

PMID- 8756444
TI  - Neural mechanisms of visual working memory in prefrontal cortex of the macaque.
AB  - Prefrontal (PF) cells were studied in monkeys performing a delayed matching to
      sample task, which requires working memory. The stimuli were complex visual
      patterns and to solve the task, the monkeys had to discriminate among the
      stimuli, maintain a memory of the sample stimulus during the delay periods, and
      evaluate whether a test stimulus matched the sample presented earlier in the
      trial. PF cells have properties consistent with a role in all three of these
      operations. Approximately 25% of the cells responded selectively to different
      visual stimuli. Half of the cells showed heightened activity during the delay
      after the sample and, for many of these cells, the magnitude of delay activity
      was selective for different samples. Finally, more than half of the cells
      responded differently to the test stimuli depending on whether they matched the
      sample. Because inferior temporal (IT) cortex also is important for working
      memory, we compared PF cells with IT cells studied in the same task. Compared
      with IT cortex, PF responses were less often stimulus-selective but conveyed more
      information about whether a given test stimulus was a match to the sample.
      Furthermore, sample-selective delay activity in PF cortex was maintained
      throughout the trial even when other test stimuli intervened during the delay,
      whereas delay activity in IT cortex was disrupted by intervening stimuli. The
      results suggest that PF cortex plays a primary role in working memory tasks and
      may be a source of feedback inputs to IT cortex, biasing activity in favor of
      behaviorally relevant stimuli.

PMID- 8756445
TI  - Implants of encapsulated human CNTF-producing fibroblasts prevent behavioral
      deficits and striatal degeneration in a rodent model of Huntington's disease.
AB  - Delivery of neurotrophic molecules to the CNS has gained considerable attention
      as a potential treatment strategy for neurological disorders. In the present
      study, a DHFR-based expression vector containing the human ciliary neurotrophic
      factor (hCNTF) was transfected into a baby hamster kidney fibroblast cell line
      (BHK). Using a polymeric device, encapsulated BHK-control cells and those
      secreting hCNTF (BHK-hCNTF) were transplanted unilaterally into the rat lateral
      ventricle. Twelve days later, the same animals received unilateral injections of
      quinolinic acid (QA; 225 nmol) into the ipsilateral striatum. After surgery,
      animals were behaviorally tested for apomorphine-induced rotation behavior and
      for skilled forelimb function using the staircase test. Rats receiving BHK-hCNTF
      cells rotated significantly less than animals receiving BHK-control cells. No
      behavioral effects of hCNTF were observed on the staircase test. Nissl-stained
      sections demonstrated that BHK-hCNTF cells significantly reduced the extent of
      striatal damage produced by QA. Quantitative analysis of striatal neurons further
      demonstrated that both choline acetyltransferase- and GAD-immunoreactive neurons
      were protected by BHK-hCNTF implants. In contrast, a similar loss of NADPH
      diaphorase-positive cells was observed in the striatum of both implant groups.
      Analysis of retrieved capsules revealed numerous viable and mitotically active
      BHK cells that continued to secrete hCNTF. These results support the concepts
      that implants of polymer-encapsulated hCNTF-releasing cells can be used to
      protect striatal neurons from excitotoxic damage and that this strategy may
      ultimately prove relevant for the treatment of Huntington's disease.

PMID- 8756446
TI  - Melanocortin antagonists define two distinct pathways of cardiovascular control
      by alpha- and gamma-melanocyte-stimulating hormones.
AB  - Melanocortin peptides and at least two subtypes of melanocortin receptors (MC3-R
      and MC4-R) are present in brain regions involved in cardiovascular regulation. In
      urethane-anesthetized rats, unilateral microinjection of alpha-melanocyte
      stimulating hormone (MSH) into the medullary dorsal-vagal complex (DVC) causes
      dose-dependent (125-250 pmol) hypotension and bradycardia, whereas gamma-MSH is
      less effective. The effects of alpha-MSH are inhibited by microinjection to the
      same site of the novel MG4-R/MC3-R antagonist SHU9119 (2-100 pmol) but not
      naloxone (270 pmol), whereas the similar effects of intra-DVC injection of beta
      endorphin (1 pmol) are inhibited by naloxone and not by SHU9119. Hypotensive and
      bradycardic responses to electrical stimulation of the arcuate nucleus also are
      inhibited by ipsilateral intra-DVC microinjection of SHU9119. gamma-MSH and
      ACTH(4-10), but not alpha-MSH, elicit dose-dependent (0.1-12.5 nmol) pressor and
      tachycardic effects, which are much more pronounced after intracarotid than after
      intravenous administration. The effects of gamma-MSH (1.25 nmol) are not
      inhibited by the intracarotid injection of SHU9119 (1.25-12.5 nmol) or the novel
      MC3-R antagonist SHU9005 (1.25-12.5 nmol). We conclude that the hypotension and
      bradycardia elicited by the release of alpha-MSH from arcuate neurons is mediated
      by neural melanocortin receptors (MC4-R/MC3-R) located in the DVC, whereas the
      similar effects of beta-endorphin, a peptide derived from the same precursor, are
      mediated by opiate receptors at the same site. In contrast, neither MC3-R nor MC4
      R is involved in the centrally mediated pressor and tachycardic actions of gamma
      MSH, which, likely, are mediated by an as yet unidentified receptor.

PMID- 8756447
TI  - Collateral sprouting of uninjured primary afferent A-fibers into the superficial
      dorsal horn of the adult rat spinal cord after topical capsaicin treatment to the
      sciatic nerve.
AB  - That terminals of uninjured primary sensory neurons terminating in the dorsal
      horn of the spinal cord can collaterally sprout was first suggested by Liu and
      Chambers (1958), but this has since been disputed. Recently, horseradish
      peroxidase conjugated to the B subunit of cholera toxin (B-HRP) and intracellular
      HRP injections have shown that sciatic nerve section or crush produces a long
      lasting rearrangement in the organization of primary afferent central terminals,
      with A-fibers sprouting into lamina II, a region that normally receives only C
      fiber input (Woolf et al., 1992). The mechanism of this A-fiber sprouting has
      been thought to involve injury-induced C-fiber transganglionic degeneration
      combined with myelinated A-fibers being conditioned into a regenerative growth
      state. In this study, we ask whether C-fiber degeneration and A-fiber
      conditioning are both necessary for the sprouting of A-fibers into lamina II.
      Local application of the C-fiber-specific neurotoxin capsaicin to the sciatic
      nerve has previously been shown to result in C-fiber damage and degenerative
      atrophy in lamina II. We have used B-HRP to transganglionically label A-fiber
      central terminals and have shown that 2 weeks after topical capsaicin treatment
      to the sciatic nerve, the pattern of B-HRP staining in the dorsal horn is
      indistinguishable from that seen after axotomy, with lamina II displaying novel
      staining in the identical region containing capsaicin-treated C-fiber central
      terminals. These results suggest that after C-fiber injury, uninjured A-fiber
      central terminals can collaterally sprout into lamina II of the dorsal horn. This
      phenomenon may help to explain the pain associated with C-fiber neuropathy.

PMID- 8756448
TI  - Synchronous activity in locus coeruleus results from dendritic interactions in
      pericoerulear regions.
AB  - Locus coeruleus (LC) neurons in brain slices from adult rats were studied using
      intracellular and extracellular recording to investigate synchronous activity.
      Spontaneous field potentials were recorded with extracellular electrodes in
      solutions containing tetraethylammonium chloride (10 mM) and BaCl2, (1 mM). These
      field potentials were found throughout but not outside the LC cell body region.
      No field potentials were observed in control solutions. Paired recordings showed
      that field potentials were synchronous in all areas of the LC. The synchronous
      activity was resistant to tetrodotoxin (1 microM) and to the neurotransmitter
      receptor blockers D-2-amino-5-phosphonopentanoic acid, bicuculline, 6-cyano-7
      nitroquinoxaline-2,3-dione, idazoxan, and strychnine, suggesting that this
      activity was not synaptically driven. Field potentials were also synchronous with
      oscillations in membrane potential recorded with intracellular electrodes. The
      oscillations in membrane potential were 5-30 mV in amplitude and had a biphasic
      wave-form. Neither the frequency nor the waveform of the oscillations was
      dependent on the membrane potential. The glycynhetinic acid derivative
      carbenoxolone and intracellular acidification with CO2 disrupted synchronous
      activity, suggesting a role of electrotonic coupling. When the cell body region
      of the LC was isolated from the pericoerulear dendritic regions by sectioning the
      size rostral and caudal to the cell body region, synchronous activity was reduced
      or abolished. Dendritic interaction in the pericoerulear region was also
      indicated by improved voltage control of the opioid-induced potassium current, as
      indicated by a shift in the reversal potential to the potassium equilibrium
      potential. The results suggest that electrical interactions between dendrites
      outside the cell body region can account for synchronous activity within the
      nucleus.

PMID- 8756449
TI  - Differential sensitivity of human visual cortex to faces, letterstrings, and
      textures: a functional magnetic resonance imaging study.
AB  - Twelve normal subjects viewed alternating sequences of unfamiliar faces,
      unpronounceable nonword letterstrings, and textures while echoplanar functional
      magnetic resonance images were acquired in seven slices extending from the
      posterior margin of the splenium to near the occipital pole. These stimuli were
      chosen to elicit initial category-specific processing in extrastriate cortex
      while minimizing semantic processing. Overall, faces evoked more activation than
      did letterstrings. Comparing hemispheres, faces evoked greater activation in the
      right than the left hemisphere, whereas letterstrings evoked greater activation
      in the left than the right hemisphere. Faces primarily activated the fusiform
      gyrus bilaterally, and also activated the right occipitotemporal and inferior
      occipital sulci and a region of lateral cortex centered in the middle temporal
      gyrus. Letterstrings primarily activated the left occipitotemporal and inferior
      occipital sulci. Textures primarily activated portions of the collateral sulcus.
      In the left hemisphere, 9 of the 12 subjects showed a characteristic pattern in
      which faces activated a discrete region of the lateral fusiform gyrus, whereas
      letterstrings activated a nearby region of cortex within the occipitotemporal and
      inferior occipital sulci. These results suggest that different regions of ventral
      extrastriate cortex are specialized for processing the perceptual features of
      faces and letterstrings, and that these regions are intermediate between earlier
      processing in striate and peristriate cortex, and later lexical, semantic, and
      associative processing in downstream cortical regions.

PMID- 8756450
TI  - Behavioral and neurochemical recovery from partial 6-hydroxydopamine lesions of
      the substantia nigra is blocked by daily treatment with glutamate receptor
      antagonists MK-801 and CPP.
AB  - To determine whether glutamate plays a role in the recovery from lesions of the
      substantia nigra, measures of behavioral functioning and extracellular levels of
      striatal dopamine (DA) were made after partial unilateral 6-OHDA lesions in adult
      male rats. In experiments 1 and 2, animals were treated on days 1-8 after
      lesioning with the noncompetitive NMDA receptor antagonist dizocilpine maleate
      (MK-801; 0.25 mg/kg, i.p.) or saline, and in experiment 3 with the competitive
      antagonist 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP; 1.0
      mg/kg, i.p.) or saline. In experiment 1, behavior was assessed 3 and 8 d after
      lesioning before daily drug treatment; on days 9 and 10, basal extracellular DA
      and metabolites were measured in both striata using microdialysis. In experiments
      2 and 3, behavior was assessed on days 3 and 15 and microdialysis on days 16 and
      17, 8-9 d post-termination of drug treatments. On day 3, all animals turned
      ipsilateral to the lesion. On days 8 or 15, saline-treated animals showed no
      behavioral asymmetries, whereas MK-801- and CPP-treated animals turned
      ipsilaterally. In antagonist-treated animals, basal levels of extracellular DA
      were lower on the lesioned side whether measured 9-10 or 16-17 d after lesioning,
      whereas in saline-treated animals DA levels on the two sides did not differ.
      These results suggest that glutamate plays a role in the development of
      compensatory changes in the DA neurons that accompany behavioral recovery from
      partial lesions of nigrostriatal DA system.

PMID- 8756451
TI  - Haltere afferents provide direct, electrotonic input to a steering motor neuron
      in the blowfly, Calliphora.
AB  - The first basalar muscle (b1) is one of 17 small muscles in flies that control
      changes in wing stroke kinematics during steering maneuvers. The b1 is unique,
      however, in that it fires a single phase-locked spike during each wingbeat cycle.
      The phaselocked firing of the b1's motor neuron (mnb1) is thought to result from
      wingbeat-synchronous mechanosensory input, such as that originating from the
      campaniform sensilla at the base of the halteres. Halteres are sophisticated
      equilibrium organs of flies that function to detect angular rotations of the body
      during flight. We have developed a new preparation to determine whether the
      campaniform sensilla at the base of the halteres are responsible for the phasic
      activity of b1. Using intracellular recording and mechanical stimulation, we have
      found one identified haltere campaniform field (dF2) that provides strong
      synaptic input to the mnb1. This haltere to mnb1 connection consists of a fast
      and a slow component. The fast component is monosynaptic, mediated by an
      electrical synapse, and thus can follow haltere stimulation at high frequencies.
      The slow component is possibly polysynaptic, mediated by a chemical synapse, and
      fatigues at high stimulus frequencies. Thus, the fast monosynaptic electrical
      pathway between haltere afferents and mnb1 may be responsible in part for the
      phase-locked firing of b1 during flight.

PMID- 8756452
TI  - Three cases of enduring memory impairment after bilateral damage limited to the
      hippocampal formation.
AB  - Patient RB (Human amnesia and the medial temporal region: enduring memory
      impairment following a bilateral lesion limited to field CA1 of the hippocampus,
      S. Zola-Morgan, L. R. Squire, and D. G. Amaral, 1986, J Neurosci 6:2950-2967) was
      the first reported case of human amnesia in which detailed neuropsychological
      analyses and detailed postmortem neuropathological analyses demonstrated that
      damage limited to the hippocampal formation was sufficient to produce anterograde
      memory impairment. Neuropsychological and postmortem neuropathological findings
      are described here for three additional amnesic patients with bilateral damage
      limited to the hippocampal formation. Findings from these patients, taken
      together with the findings from patient RB and other amnesic patients, make three
      important points about memory. (1) Bilateral damage limited primarily to the CA1
      region of the hippocampal formation is sufficient to produce moderately severe
      anterograde memory impairment. (2) Bilateral damage beyond, the CA1 region, but
      still limited to the hippocampal formation, can produce more severe anterograde
      memory impairment. (3) Extensive, temporally graded retrograde amnesia covering
      15 years or more can occur after damage limited to the hippocampal formation.
      Findings from studies with experimental animals are consistent with the findings
      from amnesic patients. The present results substantiate the idea that severity of
      memory impairment is dependent on locus and extent of damage within the
      hippocampal formation and that damage to the hippocampal formation can cause
      temporally graded retrograde amnesia.

PMID- 8756453
TI  - Neurotoxic lesions of basolateral, but not central, amygdala interfere with
      Pavlovian second-order conditioning and reinforcer devaluation effects.
AB  - Considerable evidence suggests that various discrete nuclei within the amygdala
      complex are critically involved in the assignment of emotional significance or
      value to events through associative learning. Much of this evidence comes from
      aversive conditioning procedures. For example, lesions of either basolateral
      amygdala (ABL) or the central nucleus (CN) interfere with the acquisition or
      expression of conditioned fear. The present study examined the effects of
      selective neurotoxic lesions of either ABL or CN on the acquisition of positive
      incentive value by a conditioned stimulus (CS) with two appetitive Pavlovian
      conditioning procedures. In second-order conditioning experiments, rats first
      received light-food pairings intended to endow the light with reinforcing power.
      The acquired reinforcing power of the light was then measured by examining its
      ability to serve as a reinforcer for second-order conditioning of a tone when
      tone-light pairings were given in the absence of food. Acquisition of second
      order conditioning was impaired in rats with ABL lesions but not in rats with CN
      lesions. In reinforcer devaluation procedures, conditioned responding of rats
      with ABL lesions was insensitive to postconditioning changes in the value of the
      reinforcer, whereas rats with CN lesions, like normal rats, were able to
      spontaneously adjust their CRs to the current value of the reinforcer. The
      results of both test procedures indicate that ABL, but not CN, is part of a
      system involved in CSs' acquisition of positive incentive value. Together with
      evidence that identifies a role for CN in certain changes in attentional
      processing of CSs in conditioning, these results suggest that separate amygdala
      subsystems contribute to a variety of processes inherent in associative learning.

PMID- 8756454
TI  - An identified interneuron contributes to aspects of six different behaviors in
      Aplysia.
AB  - Previous results have indicated that the bilateral cerebral interneuron CC5
      mediates the pedal artery shortening that is a component of defensive withdrawal
      responses involving the head. Current studies suggest that CC5 contributes to
      aspects of at least six different behaviors: locomotion, head turning, defensive
      head withdrawal, local tentacular withdrawal, rhythmic feeding, and head lifting.
      In addition to receiving input from mechanoreceptors in the head, CC5 receives
      synaptic input during fictive locomotor and feeding programs. Firing of CC5
      produces widespread monosynaptic or polysynaptic actions in all ganglia in the
      animal. CC5 excites presumptive motor neurons for the neck, and its activity can
      contract neck muscles. The pedal artery shortener motor neuron (PAS), a key
      excitatory follower cell of CC5, fires during ipsilateral head turning, head
      withdrawal, tentacle withdrawal, feeding, and locomotion. For all behaviors,
      except locomotion and biting, responses of PAS were eliminated by cutting the
      ipsilateral-pleural connective, which interrupts the only direct connection of
      CC5 to the ipsilateral PAS. The data suggest that CC5 is a multifunctional
      interneuron that plays different roles during different behaviors. The neuron
      appears to be involved in producing coordinated movements of the head, involving
      both somatic and visceral muscles. For some behaviors, or for certain aspects of
      behaviors, CC5 appears to act as an individual command-like neuron; for other
      behaviors, CC5 appears to act more as an element of a distributed circuit and is
      neither necessary nor sufficient for any aspects of the behavior.

PMID- 8756455
TI  - Solution NMR evidence that the HIV-1 protease catalytic aspartyl groups have
      different ionization states in the complex formed with the asymmetric drug KNI
      272.
AB  - In order to improve the design of HIV-1 protease inhibitors, it is essential to
      understand how they interact with active site residues, particularly the
      catalytic Asp25 and Asp125 residues. KNI-272 is a promising, potent HIV-1
      protease inhibitor (K(i) approximately 5 pM), currently undergoing phase 1
      clinical trials. Because KNI-272 is asymmetric, the complex it forms with the
      homodimeric HIV-1 protease also lacks symmetry, and the two protease monomers can
      have distinct NMR spectra. Monomer specific signal assignments were obtained for
      amino acid residues in the drug binding site as well as for six of the eight Asp
      residues in the protease/KNI-272 complex. Using these assignments, the ionization
      states of the Asp carboxyl groups were determined from measurements of (a) the pD
      dependence of the chemical shifts of the Asp carboxyl carbons and (b) the H/D
      isotope effect upon the Asp carboxyl carbon chemical shifts. The results of these
      measurements indicate that the carboxyl of Asp25 is protonated while that of
      Asp125 is not protonated. These findings provide not only the first experimental
      evidence regarding the distinct protonation states of Asp25/125 in HIV-1
      protease/drug complexes, but also shed light on interactions responsible for
      inhibitor binding that should form the basis for improved drug designs.

PMID- 8756456
TI  - Structure of the native cysteine-sulfenic acid redox center of enterococcal NADH
      peroxidase refined at 2.8 A resolution.
AB  - In order to obtain the crystal structure of the flavoprotein NADH peroxidase with
      its native Cys42-sulfenic acid redox center, a strategy combining reduced
      exposure of crystals to ambient oxygen and data collection at -160 degrees C was
      applied. The structure of the native enzyme to 2.8 A resolution is described;
      these results conclusively establish the existence of the Cys42-sulfenic acid as
      the functional non-flavin redox center of the peroxidase and provide the first
      structure for any naturally occurring protein-sulfenic acid. The Cys42-sulfenic
      acid atoms C alpha-C beta-S gamma-O roughly define a planar arrangement which is
      stacked parallel to the si face of the FAD isoalloxazine and positions the
      sulfenyl oxygen atom only 3.3 A from FAD-C4A. His10-N epsilon 2 contributes a
      hydrogen bond to the sulfenic acid oxygen, at a distance of 3.2 A. Although one
      oxygen atom (OX1) of the non-native Cys42-sulfonic acid derivative identified in
      the earlier wild-type peroxidase structure was taken to represent the native
      Cys42-sulfenic acid oxygen [Stehle, T., Ahmed, S. A., Claiborne, A., & Schulz, G.
      E. (1991) J. Mol. Biol. 221, 1325-1344], this structure shows that the sulfenic
      acid oxygen does not occupy this position, nor is it hydrogen-bonded to Cys42-N
      as was OX1. Comparison of the native Cys42-sulfenic acid structure with that of
      two-electron reduced glutathione reductase provides an insight into the sulfenic
      acid FAD charge-transfer interaction observed with both wild-type and His10
      mutant peroxidases. A model of the E.NADH intermediate recently observed in
      stopped-flow analyses of the enzyme [Crane, E. J., III, Parsonage, D., Poole, L.
      B., & Claiborne, A. (1995) Biochemistry 34, 14114-14124] has also been generated
      to assist in analyzing the chemical mechanism of sulfenic acid reduction.

PMID- 8756457
TI  - The pKa of the general acid/base carboxyl group of a glycosidase cycles during
      catalysis: a 13C-NMR study of bacillus circulans xylanase.
AB  - The 20 kDa xylanase from Bacillus circulans carries out hydrolysis of xylan via a
      two-step mechanism involving a covalent glycosyl-enzyme intermediate. In this
      double-displacement reaction, Glu78 functions as a nucleophile to form the
      intermediate, while Glu172 acts as a general acid catalyst during glycosylation,
      protonating the departing aglycone, and then as a general base during
      deglycosylation, deprotonating the attacking water. The dual role of Glu172
      places specific demands upon its ionization states and hence pKa values. 13C-NMR
      titrations of xylanase, labeled with [delta-13C]glutamic acid, have revealed pKa
      values of 4.6 and 6.7 for Glu78 and Glu172, respectively. These agree well with
      the apparent pKa values obtained from a study of the pH dependence of kcat/Km and
      demonstrate that, at the enzyme's pH optimum of 5.7, the nucleophile Glu78 is
      deprotonated and the general acid Glu172 initially protonated. Remarkably, the
      pKa for Glu172 drops to 4.2 in a trapped covalent glycosyl-enzyme intermediate,
      formed by reaction with 2', 4'-dinitrophenyl 2-deoxy-2-fluoro-beta-xylobioside
      [Miao et al. (1994) Biochemistry 33, 7027-7032]. A similar pKa is measured for
      Glu172 when a glutamine is present at position 78. This large decrease in pKa of
      approximately 2.5 units is consistent with the role of Glu172 as a general base
      catalyst in the deglycosylation step and appears to be a consequence of both
      reduced electrostatic repulsion due to neutralization of Glu78 and a
      conformational change in the protein. Such "pKa cycling" during catalysis is
      likely to be a common phenomenon in glycosidases.

PMID- 8756458
TI  - Conversion of serine-114 to cysteine-114 and the role of the active site
      nucleophile in acyl transfer by myristoyl-ACP thioesterase from Vibrio harveyi.
AB  - The lux-specific myristoyl-ACP thioesterase (LuxD) is responsible for diverting
      myristic acid into the luminescent system and can function as an esterase and
      transferase as well as cleave myristoyl-CoA and other thioesters. The recently
      elucidated crystal structure of the enzyme shows that it belongs to the
      alpha/beta hydrolase family and that it contains a typical catalytic triad
      composed of Asp211, His241, and Ser114. What is unusual is that the nucleophilic
      S114 is not contained within the esterase consensus motif GXSXG although the
      stereochemistry of the turn involving S114 is almost identical to the
      nucleophilic elbow found in alpha/beta hydrolases. In contrast to mammalian
      thioesterases, deacylation of LuxD was the rate-limiting step, with the level of
      acylated enzyme formed on reaction with myristoyl-CoA and the pre-steady-state
      burst of p-nitrophenol on cleavage of p-nitrophenyl myristate both being 0.7
      mol/mol. Cold chase experiments showed that the deacylation rate of LuxD
      corresponded closely to the turnover rate of the enzyme with ester or thioester
      substrates. Replacement of S114 by a cysteine residue generated a mutant (S114C)
      that was acylated with the same pH dependence as LuxD but had greatly diminished
      capacity to transfer acyl groups to water or glycerol. The acyl group could be
      removed from the S114C mutant by neutral hydroxylamine, showing that a cysteine
      residue had been acylated. Mutation of H241 creating the double mutant,
      S114C.H241N, decreased acylation of the cysteine residue. These results provide
      direct kinetic and chemical evidence that S114 is the site of acylation linked to
      H241 in the charge relay system and have led to the recognition of a more general
      consensus motif flanking the nucleophilic serine in thioesterases.

PMID- 8756459
TI  - Analysis of the effects of CRABP I expression on the RA-induced transcription
      mediated by retinoid receptors.
AB  - The involvement of cellular retinoic acid-binding protein I (CRABP I) in the RA
      signaling was investigated by examining its effects on the interaction of
      retinoid receptors (RARs and RXRs) with RA-response elements (RAREs) as well as
      on the RA-induced transcription mediated by retinoid receptors. Analysis of the
      expression of mouse CRABP I from a cDNA expression plasmid in COS-1 cells
      revealed that this protein was about 5-fold more abundant in cytosol than in
      nuclei. The identity and the localization of CRABP I in the cytoplasm as well as
      the nuclei were also confirmed by the immunoperoxidase staining of the
      transfected COS-1 cells with CRABP I-specific antibody. When the nuclear extract
      containing a 10-fold molar excess of CRABP I was incubated with RAR alpha extract
      in the presence of [3H]RA and resolved on an FPLC size-exclusion column, a 20%
      decrease in the bound radioactivity in the RAR alpha fraction was accompanied by
      a proportional increase in the CRABP I fraction. In contrast, the addition of
      CRABP I did not significantly affect the interaction of RAR alpha or RAR alpha
      RXR alpha heterodimers with RAREs. Moreover, the coexpression of CRABP I in CV-1
      cells did not markedly inhibit or enhance the transcription activated by RARs and
      RAR alpha-RXR alpha heterodimers under RA concentrations ranging from 10(-10) to
      10(-6) M. These results demonstrate that CRABP I, while it might be important for
      RA homeostasis, is not directly involved in the retinoid receptor-mediated RA
      signaling pathway.

PMID- 8756460
TI  - Minor-groove recognition of double-stranded RNA by the double-stranded RNA
      binding domain from the RNA-activated protein kinase PKR.
AB  - The human double-stranded RNA- (dsRNA) activated protein kinase (PKR) has a dsRNA
      binding domain (dsRBD) that contains two tandem copies of the dsRNA-binding motif
      (dsRBM). The minimal-length polypeptide required to bind dsRNA contains both
      dsRBMs, as determined by mobility-shift and filter-binding assays. Mobility-shift
      experiments indicate binding requires a minimum of 16 base pairs of dsRNA, while
      a minimal-length site for saturation of longer RNAs is 11 base pairs. Bulge
      defects in the helix disfavor binding, and single-stranded tails do not strongly
      influence the dsRNA length requirement. These polypeptides do not bind an RNA-DNA
      hybrid duplex or dsDNA as judged by either mobility-shift or competition
      experiments, suggesting 2'-OH contacts on both strands of the duplex stabilize
      binding. Related experiments on chimeric duplexes in which specific sets of 2'
      OHs are substituted with 2'-H or 2'-OCH3 reveal that the 2'-OHs required for
      binding are located along the entire 11 basepair site. These results are
      supported by Fe(II) EDTA footprinting experiments that show protein-dependent
      protection of the minor groove of dsRNA. The dependence of dsRNA-protein binding
      on salt concentration suggests that only one ionic contact is made between the
      protein and dsRNA phosphate backbone and that at physiological salt
      concentrations 90% of the free energy of binding is nonelectrostatic. Thus, the
      specificity of PKR for dsRNA over RNA-DNA hybrids and dsDNA is largely due to
      molecular recognition of a network of 2'-OHs involving both strands of dsRNA and
      present along the entire 11 base-pair site.

PMID- 8756461
TI  - A eubacterial Mycobacterium tuberculosis tRNA synthetase is eukaryote-like and
      resistant to a eubacterial-specific antisynthetase drug.
AB  - We report here the cloning and primary structure of Mycobacterium tuberculosis
      isoleucyl-tRNA synthetase. The predicted 1035-amino acid protein is significantly
      more similar in sequence to eukaryote cytoplasmic than to other eubacterial
      isoleucyl-tRNA synthetases. This similarity correlates with the enzyme being
      resistant to pseudomonic acid A, a potent inhibitor of Escherichia coli and other
      eubacterial isoleucyl-tRNA synthetases, but not of eukaryote cytoplasmic enzymes.
      Consistent with its eukaryote-like features, and unlike E. coli isoleucyl-tRNA
      synthetase, the M. tuberculosis enzyme charged yeast isoleucine tRNA. In spite of
      these eukaryote-like features, M. tuberculosis isoleucyl-tRNA synthetase
      exhibited highly specific cross-species aminoacylation, as demonstrated by its
      ability to complement isoleucyl-tRNA synthetase-deficient mutants of E. coli.
      When introduced into a pseudomonic acid-sensitive wild-type strain of E. coli,
      the M. tuberculosis enzyme conferred trans-dominant resistance to the drug. The
      results demonstrate that the sequence of a tRNA synthetase could have predictive
      value with respect to the interaction of that synthetase with a specific
      inhibitor. The results also demonstrate that mobilization of a pathogen's gene
      for a drug-resistant protein target can spread resistance to other, normally drug
      sensitive pathogens infecting the same host.

PMID- 8756462
TI  - Repair of cisplatin--DNA adducts by the mammalian excision nuclease.
AB  - Nucleotide excision repair is one of the many cellular defense mechanisms against
      the toxic effects of cisplatin. An in vitro excision repair assay employing
      mammalian cell-free extracts was used to determine that the 1,2-d(ApG)
      intrastrand cross-link, a prevalent cisplatin-DNA adduct, is excised by the
      excinuclease from a site-specifically modified oligonucleotide 156 base pairs in
      length. Repair of the minor interstrand d(G)/d(G) cross-link was not detected by
      using this system. Proteins containing the high mobility group (HMG) domain DNA
      binding motif, in particular, rat HMG1 and a murine testis-specific HMG-domain
      protein, specifically inhibit excision repair of the intrastrand 1,2-d(GpG) and 
      d(ApG) cross-links. This effect was also exhibited by a single HMG domain from
      HMG1. Similar inhibition of repair of a site-specific 1,2-d(GpG) intrastrand
      cross-link by an HMG-domain protein also occurred in a reconstituted system
      containing highly purified repair factors. These results indicate that HMG-domain
      proteins can block excision repair of the major cisplatin-DNA adducts and suggest
      that such an activity could contribute to the unique sensitivity of certain
      tumors to the drug. The reconstituted excinuclease was more efficient at excising
      the 1,3-d(GpTpG) intrastrand adduct than either the 1,2-d(GpG) or d(ApG)
      intrastrand adducts, in agreement with previous experiments using whole cell
      extracts [Huang, J. -C., Zamble, D. B., Reardon, J. T., Lippard, S. J., Sancar,
      A. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 10394-10398]. This result suggests
      that structural differences among the platinated DNA substrates, and not the
      presence of unidentified cellular factors, determine the relative excision repair
      rates of cisplatin-DNA intrastrand cross-links in the whole cell extracts.

PMID- 8756463
TI  - Changing a leucine to a lysine residue makes NaeI endonuclease hypersensitive to
      DNA intercalative drugs.
AB  - A single amino acid change transforms restriction enzyme NaeI to a topoisomerase
      and recombinase (NaeI-L43K) that shows no sequence similarity to these protein
      families. This transformation appears to result from coupled endonuclease and
      ligase domains. To further elucidate the relationship between NaeI-L43K and the
      topoisomerase protein family, we studied the effect of the topoisomerase
      inhibitors on NaeI-L43K activity. The intercalative drugs amsacrine, ellipticine,
      and daunorubicin inhibited NaeI-L43K, whereas the nonintercalating drugs
      camptothecin, VP-16, and oxolinic acid did not. Ethidium bromide also inhibited
      NaeI-L43K, implying that intercalation is responsible for its inhibition. The
      effects of the intercalative drugs on the DNA cleavage steps of NaeI and NaeI
      L43K were compared. The drugs hardly inhibited DNA cleavage by wild type NaeI but
      completely inhibited DNA cleavage by NaeI-L43K. This difference in inhibition
      demonstrates that the L43K amino acid change sensitized NaeI to these drugs. Low
      concentrations of the intercalative drugs, except for ethidium bromide, enhance
      production of topoisomerase--DNA covalent intermediates but inhibited production
      of the NaeI-L43K--DNA covalent intermediate. These results imply some unique
      differences between DNA relaxation by NaeI-L43K and DNA topoisomerase.
      Concomitant with studying inhibition of the cleavage intermediate, NaeI-L43K was
      found to covalently bond with the 5' end of the cleaved DNA strand.

PMID- 8756464
TI  - Transient and time-resolved resonance Raman investigation of photoinitiated
      electron transfer in ruthenated cytochromes c.
AB  - Ruthenation of exterior amino acid residues of heme proteins provides an
      effective means by which biological ET reactions can be studied within the
      context of highly complex protein environments. Resonance Raman spectroscopy can
      probe both ET kinetics and structural dynamics at the molecular level. Here we
      present the first comprehensive use of time-resolved and transient resonance
      Raman spectroscopies to examine photoinduced ET in cytochromes. Two ruthenated
      cytochromes c, Ru(lys72)-cyt.c and Ru(cyt102)cyt.c, were studied with TRRS using
      10 ns laser pulses and with TRRRS on a 10 ns to 10 ms time scale. It was found
      that resonance Raman protocols can effectively trace ET kinetics and associated
      heme--protein structural dynamics. Care must be exercised, however, when drawing
      comparisons to measurements made by other methods (i.e., transient absorbance).
      The TRRS studies directly probe the heme and its local environment and reveal
      that the heme dynamics accompanying ET are very rapid relative to
      phenomenological ET kinetics. The heme and its local environment evolve to their
      equilibrium (ferrous) structure in less than 10 ns subsequent to ET, with no
      evidence for the existence of metastable heme pocket geometries analogous to
      those observed in the dynamic response of hemoglobins and oxidases. Finally,
      species-specific differences are observed in the photoinduced ET kinetics and
      heme structural dynamics. However, these differences are confined to nanosecond
      or faster time scales.

PMID- 8756465
TI  - Identification of retained N-formylmethionine in bacterial recombinant mammalian
      cytochrome P450 proteins with the N-terminal sequence MALLLAVFL...: roles of
      residues 3-5 in retention and membrane topology.
AB  - An N-terminal block to Edman degradation was observed when any of five different
      mammalian cytochrome P450 (P450) proteins was expressed in Escherichia coli using
      the N-terminal sequence MALLLAVFL... This block was also seen in Salmonella
      typhimurium. With all proteins examined, the block could be removed by mild acid
      hydrolysis (0.6--6 N HCl, 23 degrees C) to expose Met as the N-terminus,
      suggesting N-formylMet retention. The N-terminal peptide of a modified P450 1A2
      ("mutant 1", containing a thrombin-sensitive site inserted at residue 25) was
      released with thrombin and analyzed by electrospray mass spectrometry and found
      to yield the M(r) expected for the N-formyl derivative (+/- 0.8 amu). The region
      of positions 3--5 was altered by random mutagenesis, and three P450 1A2
      expressing clones were analyzed for nucleotide and amino acid sequences. The
      changes from LLL were to RER (P450 1A2a), VDS (P450 1A2b), and WRH (P450 1A2c);
      these all show slightly dissimilar hydropathy plots compared to the MALLLAVFL...
      sequence. Mutant P450 1A2a had the N-terminal Met removed to yield N-terminal
      Ala; P450 1A2b contained an unmodified Met at the N-terminus; P450 1A2c had an
      approximately 80% block of the N-terminal Met. Experiments with bacterial
      membranes containing expressed P450 1A2 mutant 1 and P450 1A2 mutant 2 (thrombin
      sensitive site inserted at residue 46) suggest that thrombin site 2, but not 1,
      is sequestered in the membrane. Spheroplasts of bacteria expressing P450 1A2 and
      the mutants at positions 3--5 were treated with proteinase K; amino acid analysis
      indicated that no cleavage occurred. These results are interpreted in a model in
      which most of the mammalian P450 expressed in the bacterium is located in the
      cytosol, the region near residue 46 is in the inner membrane, the region near
      residue 25 is in the cytosol, and the N-terminus is either imbedded in the
      membrane or free in the cytosolic space, depending upon the sequence. However,
      the possibility that the differences in N-terminal processing are the result of
      direct changes in interactions with the deformylase and Met aminopeptidase cannot
      be excluded.

PMID- 8756466
TI  - Lactam bridge stabilization of alpha-helices: the role of hydrophobicity in
      controlling dimeric versus monomeric alpha-helices.
AB  - A series of lactam-bridged and linear 14 residue amphipathic alpha-helical
      peptides based on the sequence Ac-EXEALKKEXEALKK-amide were prepared in order to
      determine the effect of decreasing the hydrophobicity of the nonpolar face to
      helical content and stability. This was done by substituting position X by Ile,
      Val, and Ala. Lactam bridges spaced i to i + 4 were formed between the side
      chains of Glu3 and Lys7 and Glu10 and Lys14 while the linear noncyclized peptides
      could potentially form i to i + 4 salt bridges with the same residues. It was
      found that in all cases the lactam-bridged peptides were substantially more
      helical than the corresponding linear peptides as determined by CD spectroscopy.
      Moreover, the helical content approached 100% for the lactam-bridged peptides X =
      Ile and Ala and was greater than 80% for X = Val. For X = Ile and Val, this was
      partly due to the ability of the lactam bridges to enhance interchain
      interactions relative to the linear versions of the same sequence. Size-exclusion
      chromatography demonstrated that the Ile-based peptide associates as a dimer. The
      alanine-based lactam-bridged peptide was found to be monomeric as determined by
      concentration dependency studies and size-exclusion chromatography. Thermal
      denaturation studies in benign media indicated that the lactam-based peptides
      were very stable. The conformation of the Ala-based lactam peptide was further
      characterized by two-dimensional NMR spectroscopy and was found to be highly
      helical. The results demonstrate the ability of lactam bridges to stabilize the
      helical conformation and enhance dimerization of peptides based on a 3,4
      hydrophobic heptad repeat. The substitution of Ala residues in the hydrophobic
      face of the alpha-helix can prevent dimerization and specify monomeric helical
      structure.

PMID- 8756467
TI  - Influence of nucleotides on the cold stability of chloroplast coupling factor 1.
AB  - Chloroplast coupling factor 1 (CF1), a cold-labile enzyme, contains six
      nucleotide binding sites. These sites are located at the alpha/beta interfaces of
      the alpha 3 beta 3 heterohexamer. The cold lability of CF1 is decreased by the
      presence of nucleotides in the medium. We have studied the influence of both
      different nucleotides and different binding sites on the cold dissociation of
      CF1. To monitor the dissociation of CF1 during cold treatment, 8-anilino-1
      naphthalenesulfonic acid (ANS) was employed. The increase in ANS fluorescence
      during cold treatment is the result of increased accessibility of intersubunit
      hydrophobic regions as the complex dissociates. Mg(2+)-adenosine triphosphates,
      tightly bound to CF1, markedly stabilize the enzyme in the cold. ADP only
      protects CF1 from dissociating in the cold when it is bound to the loose sites or
      when it is bound in conjunction with Mg2+. CF1 that contained 2 mol of ADP/mol
      and little bound Mg2+ was nearly as cold labile as CF1 that contained just 0.2
      mol of ADP/mol. When about one of the two bound ADPs was replaced with adenylyl
      beta, gamma-imidodiphosphate (AMP-PNP), some protection from cold dissociation
      was observed. These results show that the site(s) occupied, as well as the
      nucleotides they contain, strongly influence(s) the structural stability of CF1.

PMID- 8756468
TI  - Identification of an active site residue of the R1 subunit of ribonucleotide
      reductase from Escherichia coli: characterization of substrate-induced
      polypeptide cleavage by C225SR1.
AB  - Incubation of the C225S mutant of the R1 subunit of ribonucleotide reductase from
      Escherichia coli with the R2 subunit and nucleoside diphosphates leads to
      fragmentation of the polypeptide backbone of R1 [Mao, S. S., Holler, T. P.,
      Bollinger, J.M., Jr., Yu, G. X., Johnston, M.I., & Stubbe, J. (1992) Biochemistry
      31, 9744--9751]. The 26 and 60 kDa cleavage fragments were purified to
      homogeneity. The 26 kDa polypeptide was digested with Lys-C, and the peptides
      were partially purified by RP-HPLC. Mass spectrometric analysis (MALDI-TOF) of
      the HPLC fractions allowed the identification of the C-terminal peptide. The
      molecular mass of this peptide (2176) revealed that serine-224 constitutes its C
      terminus, and further analysis of the distribution of its monoisotopic masses by
      FAB-MS indicated that Ser224 possesses a carboxamide rather than a carboxylate
      group. Treatment of the 60 kDa cleavage fragment with cyanogen bromide and
      subsequent MALDI-TOF analysis of the partially RP-HPLC purified peptides yielded
      a fraction containing its N-terminal peptide. This peptide was digested with
      trypsin, and the digestion mixture was purified by HPLC. Analysis of the
      fractions by MALDI-TOF identified the N-terminal peptide and determined a mass of
      2222. This mass suggested valine 226 was the N-terminal residue (modified by an
      adduct of 28 mass units). Larger amounts of the C-terminal tetrapeptide of the 60
      kDa fragment (V226LIE229) were obtained by complete digestion of the crude
      reaction mixture with endoproteinase Glu-C. The peptide mixture was then purified
      on an immunoadsorbent column containing immobilized antibodies raised against a
      synthetic peptide with the sequence KVLIE. After elution of the affinity-bound
      peptide, it was analyzed by CID-MS verifying that an adduct of 28 mass units was
      attached to valine 226. These results indicated that the amino group of Val226 is
      formylated. The localization of the residues at the cleavage site of C225SR1
      provides a biochemical identification of the active site region of the R1 subunit
      of RDPR from E.coli. The details of the mechanism of cleavage remain to be
      elucidated.

PMID- 8756469
TI  - Resonance Raman spectroscopy of nitrile hydratase, a novel iron-sulfur enzyme.
AB  - Resonance Raman spectra of Rhodococcus sp. R312 (formerly Brevibacterium sp.
      R312) nitrile hydratase, a novel non-heme iron enzyme, have a large number of
      peaks in the 300-500 cm-1 region; observation of shifts in these peaks after
      labeling with 34S shows that they arise from cysteine coordinated to the ferric
      ion in the protein. The rich Raman spectra result from coupling of the Fe-S
      stretch with cysteine side chain deformation modes; the observation of 15N
      isotope shifts in most of these peaks suggests participation of N-donor metal
      ligands and peptide backbone amide nitrogens in these modes as well. The
      aggregate 34S isotope shift is too large to result from a single cysteine ligand,
      consistent with the analysis of EXAFS data that shows two or three S-donor
      ligands [Scarrow et al. (1996) Biochemistry 35, 10078-10088]. Widespread 2H
      isotope shifts seen after exchange of the protein into 2H2O suggest the presence
      of hydrogen bonds to the coordinated cysteine sulfurs. Comparison of the
      resonance Raman spectra of nitrile hydratase prepared at pH 7.3 and 9.0 shows a
      shift of intensity into the higher-energy peaks in the spectra of the latter
      sample. This is interpreted as resulting from an increase in Fe-S bond strength
      at the higher pH and is supported by observation of a small decrease in Fe-S bond
      length in the EXAFS analysis [Scarrow et al. (1996) Biochemistry 35, 10078
      10088]. Such a decrease in Fe-S bond length is also consistent with pH dependent
      changes in EPR spectra and could reflect the loss of one or more hydrogen bonds
      to sulfur ligands.

PMID- 8756470
TI  - X-ray spectroscopy of nitrile hydratase at pH 7 and 9.
AB  - The iron K-edge X-ray absorption spectrum of Rhodococcus sp. R312 (formerly
      Brevibacterium sp. R312) nitrile hydratase in frozen solutions at pH 7 and 9 has
      been analyzed to determine details of the iron coordination. EXAFS analysis
      implies two or three sulfur ligands per iron and overall six coordination;
      together with previous EPR and ENDOR results, this implies an N3S2O ligation
      sphere. The bond lengths from EXAFS analysis [rav(Fe-S) = 2.21 A at pH 7.3;
      rav(Fe-N/O) = 1.99 A] support cis coordination of two cysteine ligands and
      conclusively rule out nitric oxide coordination to the iron, a possibility
      proposed on the basis of an FTIR difference experiment [Noguchi, T., Honda, J.,
      Nagamune, T., Sasabe, H., Inoue, Y., & Endo, I. (1995) FEBS Lett. 358, 9-12]. The
      higher-frequency EXAFS can be simulated well by inclusion of multiple scattering
      from two or three imidazole ligands; the fit to the data is improved if first
      sphere multiple scattering pathways are also included. A slight shortening (by
      0.02 +/- 0.01 A) of one or both Fe-S bonds when the pH is raised from 7.3 to 9.0
      is consistent with shifts observed in the Raman spectrum [Brennan et al. (1996)
      Biochemistry 35, 10068-10077].

PMID- 8756471
TI  - Generation of active [NiFe] hydrogenase in vitro from a nickel-free precursor
      form.
AB  - The maturation process of [NiFe] hydrogenases includes formation of the nickel
      metallocenter, proteolytic processing of the large subunit, and assembly with the
      other hydrogenase subunit(s). An in vitro system for the maturation of the large
      subunit (HycE) of hydrogenase 3 of Escherichia coli leading to an active enzyme
      was established. The system is based on extracts of an E. coli mutant lacking the
      nickel-specific transport system (nik). HycE was present in these extracts in the
      C-terminally extended precursor form devoid of nickel. Addition of nickel led to
      nickel incorporation and proteolytic processing of HycE. Under anaerobic
      conditions, hydrogenase 3 activity was subsequently generated. The maximal rate
      of the processing reaction was reached at a nickel concentration of 400 microM.
      The accessory proteins known to be involved in the maturation of HycE in vivo,
      namely HypB, HypC, HypD, HypE, HypF, and the protease HycI, are required for the
      in vitro reaction, since processing of HycE did not occur in extracts of double
      mutants affected in the nik system and in one of the accessory genes. Processing
      of HycE and generation of hydrogenase 3 activity were achieved in extracts of the
      nik- delta hycI mutant by addition of both nickel and purified HycI protease.

PMID- 8756472
TI  - Correlation between bilayer lipid dynamics and activity of the
      diglucosyldiacylglycerol synthase from Acholeplasma laidlawii membranes.
AB  - In the single membrane of Acholeplasma laidlawii a specific glucosyltransferase
      synthesize the major, lamellar-forming lipid diglucosyldiacylglycerol (DGlcDAG)
      from the major, nonlamellar-prone monoglucosyldiacylglycerol (MGlcDAG). This is
      crucial for the maintenance of phase equilibria close to a bilayer-nonbilayer
      transition and a nearly constant spontaneous curvature in the membrane lipid
      bilayer. Acyl chain order is also affected, but not kept constant.
      Phosphatidylglycerol (PG) is an essential activator, needed in substantial
      amounts by the DGlcDAG synthase, and likely to affect bilayer properties. A
      potential connection was investigated between the (i) lateral diffusion, (ii)
      domain formation of the PG activator and (iii) bilayer chain ordering (i.e., the
      hydrocarbon free volume), revealed in unilamellar liposomes by lipid probes
      containing one or two (fluorescent) pyrene acyl chains, and (iv) activity of the
      DGlcDAG synthase. Different activator, nonbilayer perturbant, and bilayer matrix
      conditions were employed. Diffusion of PG was substantially slower in a DGlcDAG
      compared to a phosphatidylcholine (PC) matrix with 18:1c chains but increased
      with the PG content in both. No obvious correlation between diffusion and enzyme
      activity, and no local concentration of PG as a function of chain ordering or
      curvature, was detected. However, an enrichment of PG activator into domains
      could be induced by a chain length mismatch between 18:1c-PG and 14:1c-PC (but
      not 22:1c-PC), even at small PG fractions. Patching was sufficient to stimulate
      enzyme activity 4-fold in relation to the activities normally valid at low PG
      concentrations. Chain order was substantially lower (i.e., free volumes larger)
      in bilayers of DGlcDAG than in bilayers of PC and increased in an additive
      fashion in both by the content of especially the nonbilayer-prone 1,3-18:1c-DAG
      but also by PG. At physiological concentrations of PG in DGlcDAG bilayers
      (approximately 20%) a good correlation was evident between increased DAG content
      and chain ordering and strongly enhanced enzyme activities, with maxima close to
      a bilayer-nonbilayer transition. It is concluded that regulation of packing
      conditions in A. laidlawii membranes by the DGlcDAG synthase seems to be governed
      not by the absolute extent of chain order but more by the spontaneous curvature
      within a certain range of conditions. Domain formation of the essential PG
      activator due to bilayer conditions is a second mechanism, potentially overriding
      the curvature effects.

PMID- 8756473
TI  - Understanding the P1' specificity of the matrix metalloproteinases: effect of S1'
      pocket mutations in matrilysin and stromelysin-1.
AB  - Matrilysin (MAT) prefers leucine over residues that have aromatic side chains at
      the P1' position of peptide and protein substrates, while stromelysin (HFS) has a
      broader specificity. The X-ray structures of these enzymes show that their
      respective S1' subsites differ primarily due to the amino acids present at
      positions 214 and 215. To examine the role that these residues play in
      determining P1' specificity, the amino acids at these positions in matrilysin
      have been replaced by those found in stromelysin (MAT: Y214L, MAT:A215V, and
      MAT:Y214L/A215V). The specificity and activity of MAT:A215V are similar to those
      of wild type matrilysin. Both MAT:Y214L and MAT:Y214L/A215V, however, have P1'
      specificities that are more similar to stromelysin than matrilysin. Specifically,
      these enzymes exhibit an 8- to 9-fold reduction in kcat/KM toward a peptide
      substrate with Leu in subsite P1' relative to wild type matrilysin. This is
      predominantly the result of an approximate 5-fold decrease in kcat. The KM values
      only partially increase toward the value observed for stromelysin. Studies of the
      pre-steady-state reaction of wild type and mutant matrilysin with substrates with
      Leu and Tyr residues in the P1' position confirm that the KM values for these
      reactions reflect KD values for substrate binding. Thus, replacement of a single
      tyrosine residue in the S1' pocket of matrilysin by leucine alters its P1'
      specificity to resemble that of stromelysin. In contrast, alteration of the S1'
      subsite of stromelysin (HFS:L214Y/V215A) to resemble matrilysin increases
      activity (i.e., higher kcat/KM) toward peptide substrates with both leucine and
      residues with aromatic side chains in the P1' position with only a partial
      increase in specificity for Leu. These increases in activity are the result of
      decreases in the KM values for these reactions.

PMID- 8756474
TI  - Effects of both shortening and lengthening the active site nucleophile of
      Bacillus circulans xylanase on catalytic activity.
AB  - The relative positioning of the two carboxyl groups at the active site of
      glycosidases is crucial to their function and the mechanism followed. The
      distance between these two groups in Bacillus circulans xylanase has been
      modified by mutagenesis of the catalytic nucleophile Glu78. An increase in the
      separation (Glu78Asp) results in a large (1600-5000-fold) reduction in the rate
      of the glycosylation step, but little change in the extent of bond cleavage or
      proton donation at the transition state. A decrease in the separation was
      achieved by selective carboxymethylation of the Glu78Cys mutant. This modified
      mutant was only 16-100-fold less active than wild-type enzyme, and its transition
      state structure was similarly unchanged. Complete removal of the carboxyl group
      (Glu78Cys) resulted in a mutant with no measurable catalytic activity.
      Furthermore, it did not even undergo the first step, glycosylation of the active
      site thiol. These results confirm the importance of precise positioning of the
      nucleophile at the active site of these enzymes.

PMID- 8756475
TI  - Evidence for overlapping active sites for 17 alpha-ethynlestradiol and bilirubin
      in the human major bilirubin UDPglucuronosyltransferase.
AB  - The human major bilirubin UDP glucuronosyltransferase (transferase), HUG-Brl, and
      its mutants were expressed in the COS-1 cells using cDNA-based pSVL expression
      units to generate isoforms for the comparison of relative activities with 17
      alpha-ethynlestradiol (17 alpha-EE) and bilirubin, its natural substrate. In
      comparison to bilirubin, 17 alpha-EE was a good substrate for HUG-Br1 under
      typical assay conditions of pH 7.2, confirming published studies [Ebner, T., et
      al. (1993) Mol. Pharmacol. 43, 649-654]. It was further shown that the estrogen
      derivative is 1.2-2-fold more effective as a substrate at pH 6.4 than at pH 7.2.
      The km for 17 alpha-EE was 40 microM under both pH conditions, while the Vmax
      values were 400 and 200 pmol per hour per 300 micrograms of protein at pH 6.4 and
      7.2, respectively. The pattern of glucuronidation was similar for both bilirubin
      and 17 alpha-EE. Previously, a ratio of 2-3-fold more activity for bilirubin
      glucuronidation at pH 6.4 versus 7.6 was established, and km values of 2.5 microM
      at both pH conditions were determined [Ritter, J.K., et al. (1993) J. Biol. Chem.
      268, 23573-23579]. In this study, the generation of 17 alpha-EE and bilirubin
      beta-glucuronides under both pH conditions was confirmed by the sensitivity of
      the products to beta-glucuronidase treatment. Concurrent glucuronidation reaction
      mixtures containing equal amounts of wild-type and mutant proteins demonstrated
      the following. P270G, V273D, and five different G276 mutants nearly or completely
      inactivated all glucuronidation at both pH levels. V273Q generated 81-94% of the
      normal activity for 17 alpha-EE and 42% of the normal activity for bilirubin
      turnover; H173R gave 37-60% of the normal turnover with both substrates, and
      V275I produced 15-24% of the normal level of glucuronide with both compounds. The
      most distinguishing amino acid tested was P176G which was approximately 50%
      normal for 17 alpha-EE at both pH conditions but was totally inactive for
      bilirubin. A second substitution, P285G, did not affect 17 alpha-EE turnover but
      was 50% normal for bilirubin. The parallel effects on the metabolism of both
      substrates by some mutants and the opposite results from two mutants are evidence
      for a common set of amino acids for their catalysis with the recruitment of
      additional amino acids to depend upon the substrate to be metabolized. Hence,
      amino acid substitutions in the protein are not necessarily universally
      inactivating.

PMID- 8756476
TI  - Circular dichroism evidence for the presence of burst-phase intermediates on the
      conformational folding pathway of ribonuclease A.
AB  - Refolding of the very-fast-folding unfolded species (Uvf) of disulfide-intact
      bovine pancreatic ribonuclease A has been monitored by circular dichroism (CD) at
      222 and 275 nm at 0.9 or 2.6 M guanidine hydrochloride, pH 7.0, and 5 degrees C.
      The refolding of Uvf represents a purely conformational folding process which is
      not complicated by cis-trans proline isomerization. The data indicate that there
      are at least two intermediates on the refolding pathway of Uvf and that both
      intermediates form in the burst phase when the refolding is monitored by CD. At
      the initiation of folding, Uvf is converted to a largely unfolded intermediate,
      termed Iu, which then undergoes a hydrophobic collapse to form the molten-globule
      like intermediate I phi. The CD values obtained for Iu and I phi indicate that IU
      has no significant secondary structure and presumably differs from Uvf by a local
      structural rearrangement, while I phi has a substantial population of secondary
      and tertiary structures, about 40%-50% of that of native.

PMID- 8756478
TI  - The release of the variant surface protein of Giardia to its soluble isoform is
      mediated by the selective cleavage of the conserved carboxy-terminal domain.
AB  - The trophozoites of Giardia duodenalis are covered by a coat composed of an
      apparently single species of a group of novel, cysteine-rich proteins. These
      variant-specific surface proteins (VSPs) can be changed by sequential expression
      of different VSP genes, a process for which a gradual exchange of VSP molecules
      appears to be required. In the present study, we have examined the in vitro
      release of one of these VSPs (VSP4A1, formerly named CRISP-90) expressed by a
      sheep-derived variant Giardia clone. During in vitro incubation of the cloned
      trophozoites, the membrane-associated form of VSP4A1 (mVSP4A1) was specifically
      converted to a water-soluble isoform that was continuously released into the
      culture medium. The time required for mVSP4A1 to decline to half of the initial
      amount was 7.8 h. Analysis of the two purified protein species by mass
      spectrometry revealed molecular mass values of 68,991 Da for mVSP4A1 and of
      65,425 Da for its soluble counterpart. Amino-terminal sequencing and metabolic
      labeling experiments indicated that the release of mVSP4A1 was associated with
      the cleavage of a carboxy-terminal peptide carrying the palmitic acid recently
      demonstrated to be attached to mVSP4A1. Calculations using the molecular mass and
      predicted amino acid sequence data indicated that fragmentation of the protein
      possibly occurs at a site located between the lysine and serine residues of the
      highly conserved NKSGLS motif directly preceding the hydrophobic sequence
      previously postulated to serve as a membrane anchoring domain of other VSP
      molecules. The observed processing of the membrane-associated VSP to its soluble
      isoform is assumed to be an essential requirement for the ability of the parasite
      to undergo surface antigenic variation and thus for its establishment and
      survival within the vertebrate host.

PMID- 8756477
TI  - A natural kinase-deficient variant of fibroblast growth factor receptor 1.
AB  - A fibroblast growth factor receptor 1 variant missing 37 amino acids from the
      carboxy-terminal tyrosine kinase catalytic domain was discovered in human lung
      fibroblasts and several other human cell lines. The receptor variant binds
      specifically to acidic fibroblast growth factor but has no tyrosine kinase
      activity. It was found that cellular transfectants expressing the fibroblast
      growth factor receptor 1 variant are mitogenically inactive and ligand binding to
      the receptor causes neither receptor autophosphorylation nor phospholipase C
      gamma transphosphorylation. The fibroblast growth factor receptor 1 variant
      therefore represents an inactive receptor for acidic fibroblast growth factor.
      Since both kinase and kinase-deficient receptor forms are expressed in cells, it
      is conceivable that the kinase-deficient receptor plays an important role in
      regulating cellular responses elicited by acidic fibroblast growth factor
      stimulation.

PMID- 8756479
TI  - Chemomechanical transduction in the actomyosin molecular motor by 2',3'
      dideoxydidehydro-ATP and characterization of its interaction with myosin
      subfragment 1 in the presence and absence of actin.
AB  - The effect of torsional freedom about the N-glycoside bond of ATP in the ability
      of the nucleoside triphosphate to support chemomechanical transduction (Takenaka
      et al., 1978) has been investigated by examining the ability of the nucleotide
      analogue 2',3'-dideoxy-2',3'-didehydro-ATP (1b, enf-ATP) to act as a substrate
      for myosin subfragment 1 in the presence and absence of actin and to support
      actin sliding in the standard in vitro motility assay. By converting the ribosyl
      ring of the natural substrate to the rigid and almost planar enofuranosyl ring,
      effects on torsional freedom about the N-glycoside bond due to changes in ribosyl
      ring pucker and/or by steric interferences of the protons attached to the 2' and
      3' carbons are eliminated allowing for increased torsional freedom about the N
      glycoside bond. The data indicate that this enofuranosyl analogue is an excellent
      substrate for subfragment 1 and actosubfragment 1 and produces actin sliding
      velocities which are twice as fast as those observed with ATP in the standard in
      vitro motility assay. The analogue diphosphate is trapped in S1 by the common
      P(i) analogues, but the rate of formation of the ternary complex formed with Vi
      is very slow compared to that observed with MgADP. Similar conformations of S1
      are formed with Mg.enf-ATP and MgATP under steady-state conditions, but S1 with
      bound Mg.enf-ADP differs significantly from that observed with MgADP.

PMID- 8756480
TI  - Orientation of paramagnetic probes attached to gizzard regulatory light chain
      bound to myosin heads in rabbit skeletal muscle.
AB  - The orientation of the myosin neck was monitored using electron paramagnetic
      resonance (EPR) spectroscopy. Gizzard regulatory light chain was labeled with a
      nitroxide spin probe and exchanged for the native subunit, located in the myosin
      neck, in rabbit psoas muscle fibers. The EPR spectra of rigor fibers indicated a
      substantial degree of probe immobilization and showed a strong dependence on the
      orientation of the fiber axis relative to the magnetic field, indicating that the
      neck was ordered in this state. Spectra of relaxed fibers at 24 degrees C showed
      that the neck was disordered, but the spectra of relaxed fibers at 4 degrees C
      indicated that the neck was partially ordered. Active fibers at the two
      temperatures produced spectra identical to relaxed fibers, indicating that no
      novel angles could be seen in the neck during the powerstroke. Proteolytic
      fragments of myosin, S1 and HMM, were exchanged with labeled light chains and
      bound to thin filaments in unlabeled fibers. The distribution of probe
      orientations for HMM was identical to that of labeled rigor fibers, while S1
      showed a slightly different distribution, suggesting that the neck is distorted
      (by a few degrees) by the interactions of the two heads of myosin when bound to
      actin.

PMID- 8756481
TI  - Monoclonal antibody 4B1 alters the pKa of a carboxylic acid at position 325
      (helix X) of the lactose permease of Escherichia coli.
AB  - A carboxylic acid at position 325 in helix X is obligatory for lactose/H+ symport
      at a step corresponding to deprotonation of lactose permease [Carrasco, N. et al.
      (1989) Biochemistry 28, 2533-2539]. In this paper, pH profiles for active
      transport, efflux, and equilibrium exchange are analyzed for wild-type permease
      and mutant Glu325-->Asp. With respect to active transport and efflux down a
      concentration gradient, both of which involve net H+ translocation and are
      defective in the mutant, the wild-type and the mutant exhibit similar profiles,
      and at no pH is the mutant stimulated relative to the wild-type. Strikingly,
      exchange which does not involve H+ translocation is comparable in the wild-type
      and the Glu325-->Asp mutant below pH 7.5. Above pH 7.5, however, the exchange
      activity of the mutant is progressively and reversibly inhibited with a midpoint
      at about pH 8.5; while the exchange activity of wild-type permease is only mildly
      decreased above pH 9.5, and exchange by Glu325-->Ala or Glu325-->Gln permease is
      comparable to wild-type and unaffected by pH. The findings are consistent with
      the idea that translocation of the ternary complex between the permease, lactose,
      and H+ does not tolerate a negative charge at position 325. In wild-type
      permease, the electrostatic interaction between Glu325 (helix X) and Arg302
      (helix IX) is sufficiently strong that the carboxylate is unaffected by pH. In
      contrast, with Asp at position 325, the electrostatic interaction is broken, the
      carboxylate becomes protonated, and the acid exhibits a pKa of about 8.5.
      Monoclonal antibody 4B1 binds to the periplasmic loop between helices VII and
      VIII of the permease [Sun, J. et al. (1996) Biochemistry 35, 990-998] and mimics
      the Glu325 mutants. Dramatically, 4B1 shifts the apparent pKa for exchange from
      about pH 8.5 to 7.5 in the Glu325-->Asp mutant with little or no effect on the
      wild-type or the Glu325-->Ala mutant. The findings are consistent with the
      conclusion that the uncoupling effect of 4B1 involves a conformational change in
      helix VII and/or VIII that secondarily alters the pKa of the essential carboxylic
      acid at position 325.

PMID- 8756482
TI  - Accelerated deamination of cytosine residues in UV-induced cyclobutane pyrimidine
      dimers leads to CC-->TT transitions.
AB  - The rate of UV-induced deamination of cytosine to uracil at a specific site in
      double-stranded (ds) DNA was monitored using a genetic reversion assay.
      M13mp2C141 ds DNA was exposed to 160 J/m2 UV (254 nm), incubated at 37 degrees C,
      pH 7.4, for various time intervals to allow for deamination, and treated with
      Escherichia coli photolyase in the presence of 365 nm light to reverse
      cyclobutane-type pyrimidine dimers. Upon transfection into uracil-glycosylase
      deficient (ung-) E. coli cells, the mutation (i.e., reversion) frequencies in the
      CCCC target sequence increased greatly with post-UV time of incubation at 37
      degrees C, nearly doubling every day that the DNA had been held at 37 degrees C.
      After 8 days, the reversion frequencies had increased by two orders of magnitude
      upon transfection into ung- cells, relative to isogenic ung+ cells, indicating
      that most of the mutations arising in UV/photolyase-treated ds DNA were C-->T
      mutations mediated by a uracil intermediate. Sequencing of the revertants
      revealed that all mutations were single C-->T or tandem double CC-->TT mutations.
      An increasing percentage of tandem double CC-->TT mutations was found with longer
      post-UV incubation times, yet none occurred if the post-UV delay time step was
      omitted before photoreversal. After a 4-day delay between UV and photoreversal at
      37 degrees C, greater than 84% of the total revertants had tandem double CC-->TT
      mutations. Thus, the generation of a tandem double mutation is a time-dependent
      process that arises in DNA after the initial UV exposure. The rate of appearance
      (with a pseudo-first-order rate constant ca. 10(-6) s-1) of tandem double
      mutations during incubation of UV-irradiated DNA is inconsistent with two random,
      independently occurring mutational events and suggests a concerted deamination of
      both residues in a tandem cytosine pyrimidine (C < > C) dimer. Considering that
      deamination in a C < > C dimer occurred here with a half-life of ca. 5 days, in
      contrast to the measured half-life of ca. 20,000 years for spontaneous (non-UV
      treated) cytosine deamination for the same target, these studies show that the
      formation of pyrimidine dimers in DNA increases the rate of deamination by six
      orders of magnitude, leading to the accelerated formation of single C-->T and
      tandem double CC-->TT mutations.

PMID- 8756483
TI  - Quantitative hybridization kinetics of DNA probes to RNA in solution followed by
      diffusional fluorescence correlation analysis.
AB  - Binding kinetics in solution of six N,N,N',N'-tetramethyl-5-carboxyrhodamine
      labeled oligodeoxyribonucleotide probes to a 101mer target RNA comprising the
      primer binding site for HIV-1 reverse transcriptase were characterized using
      fluorescence correlation spectroscopy (FCS). FCS allows a sensitive, non
      radioactive real time observation of hybridization of probes to the RNA target in
      the buffer of choice without separation of free and bound probe. The binding
      process could directly be monitored by the change in translational diffusion time
      of the 17mer to 37mer DNA probe upon specific hybridization with the larger RNA
      target. The characteristic diffusion time through a laser-illuminated open volume
      element with 0.5 micron in diameter increased from 0.13-0.2 ms (free) to 0.37
      0.50 ms (bound), depending on the probe. Hybridization was approximated by
      biphasic irreversible second-order reaction kinetics, yielding first-phase
      association rate constants between 3 x 10(4) and 1.5 x 10(6) M-1 s-1 for the
      different probes. These varying initial rates reflected the secondary structures
      of probes and target sites, being consistent with a hypothetical binding pathway
      starting from loop-loop interactions in a kissing complex, and completion of
      hybridization requiring an additional interaction involving single-stranded
      regions of both probe and target. FCS thus permits rapid screening for suitable
      antisense nucleic acids directed against an important target like HIV-1 RNA with
      low consumption of probes and target.

PMID- 8756484
TI  - Characterization of two recombinant PDE3 (cGMP-inhibited cyclic nucleotide
      phosphodiesterase) isoforms, RcGIP1 and HcGIP2, expressed in NIH 3006 murine
      fibroblasts and Sf9 insect cells.
AB  - cDNAs encoding PDE3 [cGMP-inhibited cyclic nucleotide phosphodiesterase (cGI
      PDE)] isoforms, cGIP1 and cGIP2, have been cloned from rat (R) and human (H) cDNA
      libraries. The deduced amino acid sequences of RcGIP1 and HcGIP2 are very similar
      in their conserved catalytic domains but differ in their N-terminal regulatory
      domains [Meacci, E., et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 3721-3725;
      Taira, M., et al. (1993) J. Biol. Chem. 268, 18573-18579]. cDNAs encoding both
      rat adipocyte RcGIP1 and human myocardial HcGIP2 (full-length forms and truncated
      forms lacking much of the putative N-terminal domain) were expressed in NIH 3006
      fibroblasts and in Sf9 insect cells. The recombinant proteins exhibited the
      expected subunit molecular mass, immunologic reactivities, and characteristics of
      native membrane-associated forms of the enzymes, e.g., high affinity for cAMP
      (Km), sensitivity to the selective cGI PDE inhibitors OPC 3689 and OPC 3911 and
      to cGMP. The full-length recombinants were predominantly particulate, whereas the
      truncated HcGIP2 forms were cytosolic suggesting that N-terminal domains contain
      structural determinants important for membrane association. Both fibroblast
      RcGIP1 and authentic adipocyte cGI PDE were phosphorylated in vitro by cAMP
      dependent protein kinase; tryptic [32P]peptides released from rat adipocyte 32P
      cGI PDE and 32P-RcGIP1 exhibited identical electrophoretic profiles suggesting
      that the same peptides are phosphorylated in both.

PMID- 8756485
TI  - Purification and characterization of the human KDEL receptor.
AB  - Retention of soluble endoplasmic reticulum (ER) proteins is ensured by their
      continuous retrieval from subsequent compartments in the secretory pathway.
      Soluble ER proteins which escape to the Golgi apparatus bind to the KDEL
      receptor, a seven-transmembrane receptor, and are then returned to the
      endoplasmic reticulum. We have overexpressed the human KDEL receptor in insect
      cells using the baculovirus system. Infected cells accumulate large amounts of
      functional receptor as judged by a ligand binding assay. A hexahistidine-tagged
      version of the receptor could be purified in a single step to near homogeneity
      with high yield. After reconstitution of purified KDEL receptor into liposomes, a
      similar affinity and pH dependence for the binding of KDEL peptides was observed
      compared to the receptor in its natural environment, indicating that purified
      KDEL receptor is sufficient for specific and pH-sensitive binding of KDEL
      ligands. Determination of the receptor affinity in different lipid environments
      revealed that the receptor affinity is only slightly influenced by its lipid
      environment, suggesting that regulation of the receptor affinity by its
      surrounding lipids does not play a crucial role for the sorting of KDEL proteins.

PMID- 8756486
TI  - Degradation of chylomicron remnants by macrophages occurs via phagocytosis.
AB  - Chylomicron remnants bound to rabbit alveolar macrophages with high-affinity (Kd
      = 3.3 +/- 0.71 microgram of protein/mL). The binding of chylomicron remnants was
      competitively inhibited in the presence of unlabeled remnants and to a lesser
      extent by unlabeled low-density lipoproteins. Pretreatment of cells with either
      trypsin or pronase inhibited degradation in a dose and time dependent manner,
      suggesting involvement of a cell surface protein. Chylomicron remnants were
      degraded by alveolar macrophages from Watanabe heritable hyperlipidemic (WHHL)
      rabbits, which are devoid of LDL receptor activity. Moreover, colchicine and
      monensin which are endocytotic and lysozomal inhibitors, respectively, did not
      have any effect on the degradation of chylomicron remnants by macrophages from
      normal rabbits. The absence of divalent cations was found to enhance chylomicron
      remnant degradation by macrophages. Activated alpha 2-macroglobulin and
      lactoferrin had no effect on chylomicron remnant degradation, indicating that the
      low-density lipoprotein receptor-related protein was not involved. In addition,
      the scavenger receptor inhibitors polyinosinic acid and fucoidan increased
      degradation of chylomicron remnant-ruling out uptake as a consequence of
      lipoprotein modification. Rather, the phagocytotic inhibitor cytochalasan D was
      found to significantly decrease chylomicron remnant degradation. Collectively,
      our data show that chylomicron remnants are metabolized by phagocytotic pathways
      initiated after binding to a cell surface protein which is distinct from the LDL
      receptor, LRP, or scavenger receptors.

PMID- 8756487
TI  - Functional expression and genetic alteration of an alpha scorpion neurotoxin.
AB  - The alpha neurotoxin Lqh alpha IT is toxic to both insects and mammals but
      exhibits a bioactivity ratio favoring insects (insect/mammal approximately 2).
      With the objective of increasing this ratio by genetic manipulation of the amino
      acid sequence, a cDNA clone encoding Lqh alpha IT was used to produce recombinant
      variants of the toxin in a high efficiency bacterial expression system. The
      unmodified recombinant toxin, isolated from inclusion bodies and renatured in
      vitro, exhibited chemical and biological properties indistinguishable from those
      of the authentic native toxin. Alteration of the toxin by site-directed
      mutagenesis led to a substantial reduction in anti-mammalian toxicity (mouse LD50
      reduced 6.4-fold) but only a slight reduction (x 1.5) in the insect ED50 value
      for paralysis. The reduction in anti-mammalian toxicity was correlated with a
      approximately 2-fold reduction of its potency for slowing of sodium channel
      inactivation in mammalian neurons, while no change in mutant toxin binding
      affinity to insect neuronal receptors was registered. These results demonstrate
      for the first time expression of a recombinant sodium channel neurotoxin in
      Escherichia coli and the use of site-directed mutagenesis to improve phylogenetic
      selectivity. This recombinant approach provides a promising strategy for
      optimizing the selective toxicity of peptide neurotoxins.

PMID- 8756488
TI  - Influence of primary sequence transpositions on the folding pathways of
      ribonuclease T1.
AB  - The slow folding of circularly permuted variants of ribonuclease T1 has been
      examined using steady-state and frequency-domain fluorescence spectroscopy. The
      sequence transpositions have previously been designed by eliminating a
      restrictive Cys2-Cys10 disulfide bond, adjoining the original termini with a
      three-peptide Gly-Gly-Gly linker, and conferring new termini to four different
      solvent-exposed beta-turns interposing secondary structural elements [Garrett, J.
      B., Mullins, L. S., & Raushel, F. M. (1996) Protein Sci. 5, 204-211]. Each of the
      mutant proteins continues to be rate-limited in folding by the slow trans to cis
      isomerizations of Pro39 and Pro55, giving rise to a branched mechanism populated
      by intermediates with mixed proline isomers. However, the overall rate of folding
      is increased in accordance with the general destabilizing effect of each circular
      permutation. Steric hindrances imposed by Trp59 on the isomerization around the
      Tyr38-Pro39 peptide bond have been implicated in decelerating the folding of
      RNase T1 [Kiefhaber, T., Grunert, H.-P., Hahn, U., & Schmid, F. X. (1992)
      Proteins: Struct., Funct., Genet. 12, 171-179]; it is this tertiary restraint
      which appears to be variably relieved by the sequence transpositions. A
      fluorescence characterization of Trp59 indicates little difference between fully
      folded RNase T1 and the variants in terms of its lifetime, accessibility to
      quenchers, and rotational properties. Yet, within protein that is "completely"
      denatured, Trp59 exhibits variable flexibility, greatest within the circularly
      permuted variants folding the fastest. Such differences in the dynamic properties
      of Trp59 between each denatured protein may be direct evidence for a relative
      loosening of the tertiary fold maintaining the "deleterious" Trp59-Pro39
      interaction in the partially folded intermediates.

PMID- 8756489
TI  - Testing the correlation between delta A and delta V of protein unfolding using m
      value mutants of staphylococcal nuclease.
AB  - The application of hydrostatic pressure to aqueous protein solutions results in
      the unfolding of the protein structure because the protein-solvent system volume
      is smaller for the unfolded state. Contributions to this decrease in volume upon
      unfolding (delta Vu) derive from altered interactions of the protein with solvent
      and are presumed to include electrostriction of charged residues, elimination of
      packing defects, and hydration of hydrophobic surfaces upon unfolding. If the
      contribution of hydrophobic surface area solvation to the observed volume change
      of unfolding were large and negative, as is generally assumed, then one would
      expect to find a correlation between the amount of surface area exposed on
      unfolding, delta A(u), and the volume change, delta Vu. In order to test this
      correlation, we have determined delta Vu for two mutants of staphylococcal
      nuclease, A69T + A90S and H121P, whose unfolding by denaturant is, respectively,
      either significantly more (28%) or significantly less (28%) cooperative than that
      observed for wild-type (WT). This cooperativity coefficient or m value has been
      shown to correlate with delta A(u). If, in turn, delta Vu is correlated with
      delta A(u), we would expect the m+ mutant, A69T + A90S, to exhibit a delta Vu
      that is more negative than WT nuclease, while the delta Vu for the m- mutant,
      H121P, should be smaller in absolute value. To verify the correlation between m
      value and delta A(u) for these mutants, we determined the xylose concentration
      dependence of the stability of each mutant at atmospheric pressure and as a
      function of pressure. The efficiency of xylose stabilization was found to be much
      greater for the m+ mutant than for WT, consistent with an increase in delta A(u),
      while that of the m- mutant was found to be only slightly greater than for WT,
      indicating that other factors may contribute to the denaturant m value in this
      case. Regardless of the denaturant m value or the effect of xylose on stability,
      the volume changes upon unfolding for both mutants were found to be within error
      of that observed for WT. Thus, there does not appear to be a correlation between
      the volume change and the change in exposed surface area upon unfolding. We have
      previously shown a lack of pH dependence of the volume change, ruling out
      electrostriction as a dominant contribution to delta Vu of nuclease. These
      studies implicate either compensation between polar and nonpolar hydration or
      excluded volume effects as the major determinant for the value of delta Vu.

PMID- 8756490
TI  - Large kinetic isotope effects in methane oxidation catalyzed by methane
      monooxygenase: evidence for C-H bond cleavage in a reaction cycle intermediate.
AB  - The reduced hydroxylase component (MMOH) of soluble methane monooxygenase (MMO)
      from Methylosinus trichosporium OB3b reacts with O2 and CH4 to produce CH3OH and
      H2O in a single-turnover reaction. Transient kinetic analysis of this reaction
      has revealed at least five and probably six intermediates during the turnover
      [Lee, S.-K., Nesheim, J. C., & Lipscomb, J. D. (1993) J. Biol. Chem. 268, 21569
      21577; Liu, Y., Nesheim, J. C., Lee, S.-K., & Lipscomb, J. D. (1995) J. Biol.
      Chem. 270, 24662-24665]. One intermediate, termed compound Q, reacts with CH4 to
      yield enzyme-bound product. It is shown here that the deuterium kinetic isotope
      effect (KIE) for the reaction of compound Q with CH4 is 50-100, which is one of
      the largest effects observed to date. The rate constants for the reactions of the
      deuterated homologs of methane decrease monotonically as the deuterium content
      increases, suggesting that a large primary isotope effect dominates. The KIEs
      determined by analyzing the products after a single turnover have the following
      values: 1:1 CH4:CD4 (19); CD3H (12); CD2H2 (9); and CH3D (4). The KIE values
      determined by directly observing the reactive intermediate and by monitoring
      product ratios are all large, consistent with complete C-H bond breaking in the
      oxygenation step of the reaction. However, the differences in the KIE values
      determined by these two methods suggest that the reaction is more complex than
      currently proposed. A modified mechanism introducing the possibility of hydrogen
      atom reabstraction by an intermediate methyl radical is proposed.

PMID- 8756491
TI  - Evolution and expression of C4 photosynthesis genes.

PMID- 8756492
TI  - Arabidopsis thaliana sku mutant seedlings show exaggerated surface-dependent
      alteration in root growth vector.
AB  - Roots of wild-type Arabidopsis thaliana seedlings in the Wassilewskija (WS) and
      Landsberg erecta (Ler) ecotypes often grow aslant on vertical agar surfaces.
      Slanted root growth always occurs to the right of the gravity vector when the
      root is viewed through the agar surface, and is not observed in the Columbia
      ecotype. Right-slanted root growth is surface-dependent and does not result
      directly from directional environmental stimuli or gradients in the plane of
      skewing. We have isolated two partially dominant mutations in WS (sku1 and sku2)
      that show an exaggerated right-slanting root-growth phenotype on agar surfaces.
      The right-slanting root-growth phenotype of wild-type and mutant roots is not the
      result of diagravitropism or of an alteration in root gravitropism. It is
      accompanied by a left-handed rotation of the root about its axis within the
      elongation zone, the rate of which positively correlates with the degree of right
      slanted curvature. Our data suggest that the right-slanting root growth phenotype
      results from an endogenous structural asymmetry that expresses itself by a
      directional root-tip rotation.

PMID- 8756493
TI  - Isolation of mutations affecting the development of freezing tolerance in
      Arabidopsis thaliana (L.) Heynh.
AB  - We screened for mutations deleterious to the freezing tolerance of Arabidopsis
      thaliana (L.) Heynh. ecotype Columbia. Tolerance was assayed by the vigor and
      regrowth of intact plants after cold acclimation and freezing. From a chemically
      mutagenized population, we obtained 13 lines of mutants with highly penetrant
      phenotypes. In 5 of these, freezing sensitivity was attributable to chilling
      injury sustained during cold acclimation, but in the remaining 8 lines, the
      absence of injury prior to freezing suggested that they were affected
      specifically in the development of freezing tolerance. In backcrosses, freezing
      sensitivity from each line segregated as a single nuclear mutation.
      Complementation tests indicated that the 8 lines contained mutations in 7
      different genes. The mutants' freezing sensitivity was also detectable in the
      leakage of electrolytes from frozen leaves. However, 1 mutant line that displayed
      a strong phenotype at the whole-plant level showed a relatively weak phenotype by
      the electrolyte leakage assay.

PMID- 8756494
TI  - The cyanobacterial thioredoxin gene is required for both photoautotrophic and
      heterotrophic growth.
AB  - The gene encoding thioredoxin in the facultative heterotrophic cyanobacterium
      Synechocytis sp. PCC 6803 (trxA) has been cloned by heterologous hybridization
      using the corresponding gene trxM from the cyanobacterium Anacystis nidulans as a
      probe. The deduced amino acid sequence of trxA predicts a protein of relative
      molecular weight of 11,750 and has strong identity with its cyanobacterial
      counterparts and other m-type thioredoxins of photo-synthetic eukaryotes. The
      trxA gene has been expressed Escherichia coli as a functional protein of 12 kD
      and has been shown by western blot analysis to be the same size as in
      Synechocystis. The trxA gene is transcribed in Synechocystis as a single
      transcript of 450 nucleotides and accumulates to the same level under
      photosynthetic and heterotrophic growth conditions. The trxA gene was inactivated
      with a kanamycin-resistant cassette, and total segregation of the disrupted trxA
      gene was obtained only when the trxM gene from A. nidulans (E.D.G. Muller, B.B.
      Buchanan [1989] J Biol Chem 264: 4008-4014) was simultaneously expressed in
      Synechocytis. Our results suggest an essential role of thioredoxin not only when
      cells grow photosynthetically but also under heterotrophic conditions.

PMID- 8756495
TI  - Regulation of Arabidopsis thaliana (L.) Heynh Arginine decarboxylase by potassium
      deficiency stress.
AB  - Arginine decarboxylase (ARGdc) is the first enzyme in one of the two pathways to
      putrescine in plants. ARGdc enzyme activity has been shown to be induced by many
      environmental factors, including potassium deficiency stress. We investigated the
      mechanism for induction of ARGdc activity during potassium deficiency stress in
      Arabidopsis thaliana (L.) Heynh. We show that A. thaliana responds to potassium
      deficiency stress by increasing ARGdc activity by up to 10-fold over unstressed
      plants with a corresponding increase in putrescine levels of up to 20-fold.
      Spermidine and spermine levels do not increase proportionately. Northern analysis
      showed no increase in ARGdc mRNA levels correlated with the increase in ARGdc
      enzyme activity. Western analysis revealed that there was no difference between
      ARGdc protein levels in stressed plants compared with controls. The increase in
      ARGdc enzyme activity due to potassium deficiency stress does not appear to
      involve changes in mRNA or protein abundance.

PMID- 8756496
TI  - Cloning of a cDNA encoding cytosolic acetoacetyl-coenzyme A thiolase from radish
      by functional expression in Saccharomyces cerevisiae.
AB  - A cDNA coding for radish (Raphanus sativus L.) acetoacetyl-coenzyme A thiolase
      (AACT) was cloned by complementation of the erg10 mutation affecting AACT in
      yeast (Saccharomyces cerevisiae). The longest reading frame encodes a protein of
      406 amino acids with a predicted relative molecular weight of 42,032, with
      significant similarities to eukaryotic and prokaryotic thiolases. There is no
      evidence for the presence of a leader peptide characteristic, e.g. of glyoxysomal
      thiolase. Yeast transformants expressing the radish AACT gene placed under the
      control of the GAL1 promoter exhibited a 10-fold higher enzyme activity than a
      wild-type yeast strain after induction by galactose. This enzyme activity is
      exclusively localized in the soluble fraction but not in membranes. These data
      indicate that we have cloned a gene encoding cytoplasmic (biosynthetic) AACT.
      Genomic DNA gel blot analysis suggests the presence of a single AACT gene, which
      is expressed in all parts of the seedling. Expression in cotyledons appears to be
      light-stimulated. We present preliminary evidence that a smaller transcript
      represents an antisense species being read from the same gene.

PMID- 8756497
TI  - Proteolytic processing of class IV chitinase in the compatible interaction of
      bean roots with Fusarium solani.
AB  - Three chitinase isoenzymes, PvChiE, PvChiF, and PvChiG (molecular masses 29, 28,
      27 kD, respectively), were purified from bean (Phaseolus vulgaris L. cv Saxa)
      roots infected with the fungal pathogen Fusarium solani f. sp. phaseoli, and
      their amino acid sequence was partially determined. All sequences from all three
      isoenzymes exactly matched deduced amino acid sequences of the bean class IV
      chitinase PvChi4, formerly called PR4. The N terminus of PvChif mapped to the
      hinge region, and the N terminus of PvChiG mapped to the catalytic domain of
      PvChi4. The N terminus of PvChiE was blocked. The appearance of PvChiE, PvChiF,
      and PvChiG correlated with an increase in protease activity in infected roots,
      and they could be generated in vitro by mixing extracts with high protease
      activity with extracts containing high amounts of PvChi4. Extracts from infected
      roots prepared in the presence of protease inhibitors also contained the
      processed forms of PvChi4, indicating that processing occurred in planta and not
      as an artifact of extraction. Processing of PvChi4 was not detected in
      incompatible interactions with a nonhost strain of F. solani and in symbiotic
      interactions with Glomus mosseae, and thus may be important only in compatible
      interactions with F. solani.

PMID- 8756498
TI  - A multiple-stimuli-responsive as-1-related element of parA gene confers
      responsiveness to cadmium but not to copper.
AB  - The expression of parA, an auxin-regulated gene expressed during the culture of
      tobacco (Nicotiana tabacum L.) mesophyll protoplasts, is induced by cadmium. To
      identify the cadmium-responsive element, we examined the parA promoter using the
      GUS reporter gene. Cadmium responsiveness was retained in a 5' deletion of the
      parA promoter to -78 bp, but it was nullified by further deletion to -49bp, which
      implies that the region -49 to -78 bp contained a cadmium-responsive element.
      This region contains a sequence similar to as-1, an enhancer sequence from the
      cauliflower mosaic virus 35S RNA promoter that binds the nuclear factor ASF-1. We
      named the sequence in the parA promoter pas. Gel-shift assays revealed that pas
      and as-1 compete for the same DNA-binding nuclear protein(s). Since pentamers of
      either pas and as-1 were able to confer cadmium responsiveness on a minimal
      promoter but mutant as-1 was not, we propose that pas and as-1 are involved in
      cadmium-responsive gene expression. Neither pas nor as-1 conferred responsiveness
      to copper. The specificity of this response, involving the function of as-1
      related elements including pas, is discussed.

PMID- 8756499
TI  - Isolation and characterization of glutamine synthetase from the marine diatom
      Skeletonema costatum.
AB  - Two peaks of glutamine synthetase (GS) activity were resolved by anion-exchange
      chromatography from the marine diatom Skeletonema costatum Grev. The second peak
      of activity accounted for greater than 93% of total enzyme activity, and this
      isoform was purified over 200-fold. Results from denaturing gel electrophoresis
      and gel-filtration chromatography suggest that six 70-kD subunits constitute the
      400-kD native enzyme. The structure of the diatom GS, therefore, appears more
      similar to that of a type found in bacteria than to the type common among other
      eukaryotes. Apparent Michaelis constant values were 0.7 mM for NH4(+), 5.7 mM for
      glutamic acid, and 0.5 mM for ATP. Enzyme activity was inhibited by serine,
      alanine, glycine, phosphinothricin, and methionine sulfoximine. Polyclonal
      antiserum raised against the purified enzyme localized a single polypeptide on
      western blots of S. costatum cell lysates and recognized the denatured, native
      enzyme. Western analysis of the two peak fractions derived from anion-exchange
      chromatography demonstrated that the 70-kD protein was present only in the later
      eluting peak of enzyme activity. This form of GS does not appear to be unique to
      S. costatum, since the antiserum recognized a similar-sized protein in cell
      lysates of other chromophytic algae.

PMID- 8756500
TI  - Degradation pattern of photosystem II reaction center protein D1 in intact
      leaves. The major photoinhibition-induced cleavage site in D1 polypeptide is
      located amino terminally of the DE loop.
AB  - Photoinhibition-induced degradation of the D1 protein of the photosystem II
      reaction center was studied in intact pumpkin (Cucurbita pepo L.) leaves.
      Photoinhibition was observed to cause the cleavage of the D1 protein at two
      distinct sites. The main cleavage generated an 18-kD N-terminal and a 20-kD C
      terminal degradation fragment of the D1 protein. this cleavage site was mapped to
      be located clearly N terminally of the DE loop. The other, less-frequent cleavage
      occurred at the DE loop and produced the well-documented 23-kD, N-terminal D1
      degradation product. Furthermore, the 23-kD, N-terminal D1 fragment appears to be
      phosphorylated and can be detected only under severe photoinhibition in vivo.
      Comparison of the D1 degradation pattern after in vivo photoinhibition to that
      after in vitro acceptor-side and donor-side photoinhibition, performed with
      isolated photosystem II core particles, gives indirect evidence in support of
      donor-side photoinhibition in intact leaves.

PMID- 8756501
TI  - Mutualistic fungal endophytes express a proteinase that is homologous to
      proteases suspected to be important in fungal pathogenicity.
AB  - Many cultivated and wild grass species are hosts to mutualistic fungal
      endophytes. These associations are ecologically and agronomically significant,
      yet little is known regarding the physiological aspects of the interaction. In
      the Poa ampla/Acremonium typhinum interaction, a fungal serine proteinase, At1,
      is surprisingly abundant and may constitute 1 to 2% of the total leaf-sheath
      protein. Sequence analysis of cDNA and genomic clones indicates that proteinase
      At1 is a member of the eukaryotic subtilisin-like protease family. It is
      homologous to proteases suspected to be virulence factors in fungal pathogens of
      insects, nematodes, and other fungi. Gel blot analysis of RNA extracted from
      infected leaf-sheath tissue indicates that the proteinase At1 transcript level is
      extremely high. RNA gel blots and immunoblots of purified enzymes indicate that
      similar proteinases are produced by Epichloe festucae and Acremonium lolii, the
      fungal endophytes infecting Festuca rubra subsp. rubra and Lolium perenne,
      respectively. Fungal expression of proteinase At1-like enzymes may be a general
      feature of endophyte infection.

PMID- 8756502
TI  - Novel osmotically induced antifungal chitinases and bacterial expression of an
      active recombinant isoform.
AB  - NaCl (428 mM)-adapted tobacco (Nicotiana tabacum L. var Wisconsin 38) cells
      accumulate and secrete several antifungal chitinases. The predominant protein
      secreted to the culture medium was a 29-kD peptide that, based on internal amino
      acid sequence, was determined to be a class II acidic chitinase with similarity
      to PR-Q. The four predominant chitinases (T1, T2, T3, and T4) that accumulated
      intracellularly in 428 mM NaCl-adapted cells were purified. Based on N-terminal
      sequence analyses, two of these were identified as class I chitinase isoforms,
      one similar to the N. tomentosiformis (H. Shinshi, J.M. Neuhaus, J. Ryals, F.
      Meins [1990] Plant Mol Biol 14:357-368) protein (T1) and the other homologous to
      the N. sylvestris (Y. Fukuda, M. Ohme, H. Shinshi [1991] Plant Mol Biol 16:1-10)
      protein (T2). The other two proteins (T3 and T4) were determined to be novel
      chitinases that have sequence similarity with class I chitinases, but each lacks
      a chitin-binding domain. All four chitinases inhibited Fusarium oxysporum f. sp.
      lycopersici and Trichoderma longibrachiatum hyphal growth in vitro, although the
      isoforms containing a chitin-binding domain were somewhat more active. Conditions
      were established for the successful expression of soluble and active bacterial
      recombinant T2. Expression of soluble recombinant T2 was achieved when isopropyl
      beta-D-thiogalactopyranoside induction occurred at 18 degrees C but not at 25 or
      37 degrees C. The purified recombinant protein exhibited antifungal activity
      comparable to a class I chitinase purified from NaCl-adapted tobacco cells.

PMID- 8756503
TI  - Specificity of binding of beta-glucoside activators of ryegrass (1-->3)-beta
      glucan synthase and the synthesis of some potential photoaffinity activators.
AB  - Structure-activity relationships among glycoside activators of ryegrass (Lolium
      multiflorum) (1-->3)-beta-glucan synthase were investigated using a number of
      natural and synthetic glycosides, including some carrying photoaffinity
      functions. There is an absolute requirement for a beta-D-glycosyl moiety in the
      activator, both S- and N-glucosides are active, and the position of the
      glucosidic linkage in beta-glucose disaccharides has a significant effect on the
      affinity of binding. However, the binding requirement does not extend beyond a
      single beta-D-glucosyl residue, and beta-D-oligoglucosides are less effective
      than disaccharides. The nature of the aglycon has a major influence on the
      binding affinity. Hydrophobic aglycons lower the concentration required for half
      maximal stimulation of the enzyme obtained from an Eadie-Hofstee plot of kinetic
      data (Ka) for activation, but charge aglycons increase Ka. Relative to methyl
      beta-D-glucoside and cellobiose (Ka 1.1 mM), the most potent compounds tested
      were N-[4-(benzoyl)benzoyl]-beta-D-glucosylamine and 2'-[4
      azidosalicylamino]ethyl-1-thio-beta-D-glucoside with K(a)s of approximately 30
      microM. The latter also was tested for its potential to specifically label the
      beta-glucoside-binding site on the synthase, but under the conditions used the
      binding was found to be nonspecific.

PMID- 8756504
TI  - Two genes encode highly similar chloroplastic NADP-malic enzymes in Flaveria.
      Implications for the evolution of C4 photosynthesis.
AB  - To gain an understanding of the molecular events underlying the evolution of C4
      photosynthesis, we have undertaken as detailed study of the NADP-malic enzyme
      gene family in C4 and C3 species of Flaveria. Three genomic clones form the C4
      species Flaveria bidentis were characterized and found to encode two highly
      similar chloroplastic forms of NADP-malic enzyme, termed ME1 and ME2. Genomic
      southern blotting with gene-specific probes showed that both Me1 and Me2 are
      found in Flaveria trinervia (C4) and Flaveria pringlei (C3) as well as in F.
      bidentis. Northern blots demonstrated that Me1 expression in leaves parallels the
      degree of C4 photosynthesis in seven Flaveria species. Furthermore, whereas Me2
      was expressed at a low level in both roots and leaves of F. bidentis, Me1
      expression was seen only in leaves and was light-regulated. We discuss these
      results in the context of the evolution of C4 photosynthesis in Flaveria.

PMID- 8756505
TI  - Cold-shock regulation of the Arabidopsis TCH genes and the effects of modulating
      intracellular calcium levels.
AB  - The Arabidopsis TCH genes, which encode calmodulin-related proteins and a
      xyloglucan endotransglycosylase, are shown to be up-regulated in expression
      following cold shock. We investigated a possible role of fluctuations in
      intracellular calcium ion concentrations ([Ca2+]) in the cold-shock-induced TCH
      gene expression. Transgenic plants harboring the apoaequorin gene were generated
      to monitor [Ca2+]) and to test the necessity of cold-induced [Ca2+] increases for
      TCH expression. Cold-shock-induced [Ca2+] increases can be blocked by La3+ and
      Gd3+, putative plasma membrane Ca2+ channel blockers, and 1,2-bis(o
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, an extracellular Ca2+ chelator.
      Cold-shock-induced expression of the TCH genes is inhibited by levels of La3+,
      Gd3+, and 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, that have
      been shown to block [Ca2+] increases. These data support the hypotheses that (a)
      intracellular [Ca2+] increases following cold shock require extracellular Ca2+
      and may derive from a Ca2+ influx mediated by plasmalemma Ca2+ channels, and (b)
      cold up-regulation of expression of at least a subset of the TCH genes requires
      an intracellular [Ca2+] increase. The inhibitors are also shown to have stimulus
      independent effects on gene expression, providing strong evidence that these
      commonly used chemicals have more complex effects than generally reported.

PMID- 8756506
TI  - Two wound-inducible soybean cysteine proteinase inhibitors have greater insect
      digestive proteinase inhibitory activities than a constitutive homolog.
AB  - Diverse functions for three soybean (Glycine max L. Merr.) cysteine proteinase
      inhibitors (CysPIs) are inferred from unique characteristics of differential
      regulation of gene expression and inhibitory activities against specific Cys
      proteinases. Based on northern blot analyses, we found that the expression in
      leaves of one soybean CysPI gene (L1) was constitutive and the other two (N2 and
      R1) were induced by wounding or methyl jasmonate treatment. Induction of N2 and
      R1 transcript levels in leaves occurred coincidentally with increased papain
      inhibitory activity. Analyses of kinetic data from bacterial recombinant CysPI
      proteins indicated that soybean CysPIs are noncompetitive inhibitors of papain.
      The inhibition constants against papain of the CysPIs encoded by the wound and
      methyl jasmonate-inducible genes (57 and 21 nM for N2 and R1, respectively) were
      500 to 1000 times lower than the inhibition constant of L1 (19,000 nM). N2 and R1
      had substantially greater inhibitory activities than L1 against gut cysteine
      proteinases of the third-instar larvae of western corn rootworm and Colorado
      potato beetle. Cysteine proteinases were the predominant digestive proteolytic
      enzymes in the guts of these insects at this developmental stage. N2 and R1 were
      more inhibitory than the epoxide trans-epoxysuccinyl-L-leucylamide-(4
      guanidino)butane (E-64) against western corn rootworm gut proteinases (50%
      inhibition concentration = 50, 200, and 7000 nM for N2, R1, and E-64,
      respectively). However, N2 and R1 were less effective than E-64 against the gut
      proteinases of Colorado potato beetle. These results indicate that the wound
      inducible soybean CysPIs, N2 and R1, function in host plant defense against
      insect predation, and that substantial variation in CysPI activity against insect
      digestive proteinases exists among plant CysPI proteins.

PMID- 8756508
TI  - The electronic Plant Gene Register.

PMID- 8756507
TI  - Differential regulation of trichome formation on the adaxial and abaxial leaf
      surfaces by gibberellins and photoperiod in Arabidopsis thaliana (L.) Heynh.
AB  - In wild-type (WT) Columbia and Landsberg erecta ecotypes of Arabidopsis thaliana
      (L.) Heynh., trichomes are present on the adaxial surfaces of all rosette leaves
      but are absent from the abaxial surfaces of the first-formed leaves. We have
      determined that both long-day (LD) photoperiod and gibberellin (GA) stimulate
      trichome formation. WT plants grown in LD conditions produce the first abaxial
      trichome on earlier leaves than plants grown in short-day (SD) conditions.
      Photoperiod sensitivity of abaxial trichome formation on WT plants develops
      gradually over time, reaching the maximum sensitivity about 24 d after
      germination. Application of gibberellic acid to WT plants growing in SD
      conditions accelerates the onset of abaxial trichomes. Conversely, application of
      20 to 80 mg L-1 paclobutrazol, a GA biosynthesis inhibitor, to wild-type plants
      suppresses trichome initiation on the abaxial epidermis. The GA-deficient mutants
      ga1-5 and ga4-1 and the GA-insensitive mutant gai-1 exhibit delayed onset of
      abaxial trichomes when grown in LD conditions. The null mutant ga1-3 produces
      completely glabrous leaves when grown in SD conditions. Application of
      gibberellic acid to glabrous ga1-3 plants consistently induces earlier formation
      of trichomes on the adaxial epidermis than on the abaxial epidermis,
      demonstrating a difference between the adaxial and abaxial surfaces in their
      response to GA with regard to trichome formation.

PMID- 8756509
TI  - Ambidextrous molecules: cylindrical peptide structures formed by fusing left- and
      right-handed helices.

PMID- 8756510
TI  - Development of a model for the delta-opioid receptor pharmacophore. 4. Residue 3
      dehydrophenylalanine analogues of Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13) confirm
      required gauche orientation of aromatic side chain.
AB  - We have previously proposed a model for the delta-opioid receptor binding
      conformation of the high affinity tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13)
      based on experimental and theoretical conformational analysis of this peptide and
      a correlation of conformational preferences of further conformationally
      restricted analogues of this tetrapeptide with their receptor binding affinities.
      A key element of this model is the requirement that the Phe3 side chain exist in
      the chi 1 = -60 degrees conformation. Conformational calculations on the residue
      3 dehydrophenylalanine analogues of JOM-13 suggest that while the dehydro (Z)
      phenylalanine analogue can be superimposed easily with the proposed binding
      conformer of JOM-13, the dehydro(E)phenylalanine analogue cannot. These results
      lead to the prediction that the dehydro(Z)phenylalanine analogue should display
      similar delta-receptor binding affinity as JOM-13 while the
      dehydro(E)phenylalanine analogue is expected to bind less avidly. Synthesis and
      subsequent opioid receptor binding analysis of the dehydrophenylalanine analogues
      of JOM-13 confirm these predictions, lending support to the delta-pharmacophore
      model.

PMID- 8756511
TI  - Solution structure of regioselectively addressable functionalized templates: an
      NMR and restrained molecular dynamics investigation.
AB  - Three cyclic peptides that are Regioselectively Addressable Functionalized
      Templates (RAFT) for use in protein de novo design have been investigated using a
      combination of nmr, restrained molecular dynamics, and CD spectroscopy. These
      peptides contain up to four selectively addressable sites (orthogonally protected
      lysine side chains) or have selectively addressable faces. The results show a
      common stable conformation for templates of this kind based on two type II beta
      turns and an associated beta-sheet structure. A preferential orientation for the
      side chains is also demonstrated. The significance of these findings is discussed
      in the context of applications of RAFT that rely on their conformational rigidity
      and ability to present functionalities in a defined spatial arrangement.

PMID- 8756512
TI  - Theoretical studies of the intercalation of 9-hydroxyellipticine in DNA.
AB  - Extensive molecular dynamics (MD) simulations have been used to investigate the
      intercalative binding of 9-hydroxyellipticine to the DNA oligonucleotide
      d(ATATATATATAT)2. Four independent simulations differing in the initial
      orientation of the drug at the intercalation site were carried out, and compared
      both with each other and a control simulation of the free DNA sequence. The
      structure of the latter was compared with structures obtained from x-ray
      crystallography and nmr spectroscopy, as well as the theoretically derived
      "alternating B-DNA" model [A. Klug et al. (1979), Journal of Molecular Biology,
      Vol. 131, p. 669]. The alternation of twist angles observed in experimental
      structures was reproduced in the simulation. All four independent simulations of
      the drug-DNA intercalation complex converged in placing the pyridine ring of the
      ellipticine chromophore in the major groove; in one case this involved a 180
      degrees rotation of the drug at the intercalation site. At a more detailed level,
      the drug is seen to be capable of adopting several distinct orientations, each
      stable over a period of hundreds of pico-seconds. Despite the presence of several
      polar groups in the drug, however, no direct hydrogen bonding to the DNA occurs;
      instead, interactions between the methyl groups of the drug and the thymine bases
      at the intercalation site appear important in determining the orientational
      preferences of the drug. Comparison of the intercalation complexes with the free
      DNA sequence shows a degree of unwinding resulting from intercalation, in good
      agreement with experimental results, but spread over the three central base-pair
      steps, not confined to the intercalation site itself. Measurements of torsional
      rigidity indicate only a slight stiffening of the DNA restricted to the immediate
      site of intercalation. The structures obtained from the MD simulations were used
      to calculate theoretical CD spectra, with separate simulations giving very
      different results. This appears to indicate that given an accurate assignment of
      the main electronic transition dipole moment of the ellipticine chromophore,
      discrimination of the more realistic binding geometries may be possible. The
      relative merits of the various drug orientations observed in the simulations are
      discussed and a perpendicular orientation of the drug at the intercalation site
      is considered to be the most consistent with experimental data. While the
      simulations themselves represent a total of over 2 ns, however, the differences
      apparent between independent runs indicate that longer simulation times will be
      required before a complete, unequivocal view of DNA intercalation is obtained.

PMID- 8756513
TI  - Modified chemotactic peptides: synthesis, conformation, and activity of HCO-Thp
      Ac6c-Phe-OMe.
AB  - HCO-Thp-Ac6c-Phe-OMe (3) has been synthesized as a new analogue of the
      prototypical chemotactic agent HCO-Met-Leu-Phe-OMe (fMLP-OMe). Compound 3
      contains 4-aminotetra-hydrothiopyran-4-carboxylic acid (Thp) and 1
      aminocyclohexane-1-carboxylic acid (Ac6c) as achiral, conformationally restricted
      mimics of Met and Leu, respectively. In the crystal, the formyltripeptide adopts
      an helical conformation at the Thp and Ac6c residues, of the type alpha R and
      alpha L, respectively, whereas the C-terminal phenylalanine is quasi-extended. A
      system of two consecutive gamma-turns, centered at the first two residues, better
      explains the nmr data as compared with an alternative beta-turn structure. The
      conformation of the new analogue 3 is compared with those of two related peptides
      containing Thp as N-terminal residue. The biological activity of 3 has been
      determined on human neutrophils and compared to that of the previously studied
      model [Ac6c2] fMLP-OMe. While the above analogue is highly active in the
      superoxide anion production, the new tripeptide 3 is practically unable to elicit
      any of the tested biological activities.

PMID- 8756514
TI  - Solution conformations of pectin polysaccharides: determination of chain
      characteristics by small angle neutron scattering, viscometry, and molecular
      modeling.
AB  - The solution behavior of pectin polysaccharides has been investigated by small
      angle neutron scattering (SANS), viscosimetric, and molecular modeling studies.
      The samples used in the experimental study were obtained from apple and citrus
      and had degrees of methylation ranging from 28 to 73%, with a rhamnose content
      lying between 0.6 and 2.2%. Persistence lengths, derived from intrinsic viscosity
      measurements, ranged from 59 to 126 A, whereas those derived by SANS were between
      45 and 75 A. These values correspond to 10-17 monomer units. The modeling
      simulations were performed for both homogalacturonan itself and homogalacturonan
      carrying various degrees of rhamnose inserts (rhamnogalacturonan). This required
      the evaluation of the accessible conformational space for the eight disaccharides
      that represent the constituent repeating segments of the homogalacturonan and
      rhamnogalacturonan polysaccharides. For each dimer, complete conformational
      analysis was accomplished using the flexible residue method of the MM3 molecular
      mechanics procedure and the results used to access the configurational statistics
      of representative pectic polysaccharide chains. For homogalacturonan, an extended
      chain conformation having a persistence length of 135 A (corresponding to 30
      monomers) was predicted. The inclusion of varying amounts of rhamnose units (5
      25%) in the model in strict alternating sequence with galacturonate residues
      (equivalent to the rhamnogalacturonan "hairy region" chains) only slightly
      reduced the calculated persistence length. The extended overall chain
      conformation remained relatively unchanged as a consequence of the self
      cancellation of the kinking effects of successive paired rhamnose units.

PMID- 8756515
TI  - Catalytic subunit of cAMP-dependent protein kinase: electrostatic features and
      peptide recognition.
AB  - The electrostatic field was calculated for the mammalian cAMP-dependent protein
      kinase (PKA) catalytic subunit (C-subunit) complexed with a 20-residue peptide
      from a heat stable protein kinase inhibitor (PKI: 5-24). The electrostatic field
      was also calculated for the C-subunit complexed with a modeled heptapeptide
      substrate that has been used extensively in structure/function studies for the C
      subunit. Perturbations in the electrostatic free energy were calculated when
      single ionizable active site residues were mutated to alanine. These
      perturbations in electrostatic free energy were correlated to changes in the
      binding energy measured in a charge-to-alanine scan of the homologous yeast C
      subunit by M. J. Zoller and C. S. Gibbs [(1991) Journal of Biological Chemistry,
      Vol. 266, pp. 8923-8931; C. S. Gibbs and M. J. Zoller (1991) Biochemistry, Vol.
      30, p. 22]. This analysis indicated that the substrate binding parameters
      primarily depend on electrostatic interactions between a substrate or inhibitor
      and the C-subunit. Amino acid replacements that led to large perturbations in the
      electrostatic field are listed in the text. pKa shifts were also calculated for
      the substrate's phosphate accepting atom, the serine hydroxyl oxygen, when the
      active site ionizable residues were changed to structurally similar uncharged
      amino acids. The theoretical mutation of three active site residues caused large
      shifts in this parameter: E91Q, D166N, and D184N. The calculated pKa shifts for
      these mutants indicate that the rate of phosphotransfer should be markedly
      reduced in these cases. This prediction has been experimentally confirmed for the
      D166N mutant. The correlation between calculated electrostatic free energy
      changes and measured binding energy, and pKa shifts with phosphotransfer for C
      subunit mutants were within experimental error of the measurements. The
      calculations of electrostatic energy and delta pKa have identified previously
      unconsidered active site residues in the mammalian C-subunit that contribute to
      binding energy and phosphotransfer.

PMID- 8756516
TI  - Predicted and trifluoroethanol-induced alpha-helicity of polypeptides.
AB  - The alpha-helix stabilizing solvent 2,2,2-trifluoroethanol (TFE) is frequently
      used as a medium for determining the average alpha-helicity of polypeptides by CD
      spectroscopy. CD spectra measured in solutions containing 10, 15, 20, 50, and 90%
      (vol/vol) TFE are presented for 5 peptides that were selected to demonstrate
      possible variations in the effect of TFE concentration on the secondary
      structure. The analysis is extended to 6 further peptides whose CD spectra as
      measured in TFE are documented in the literature. The observed alpha-helicity at
      a high TFE concentration is compared with the alpha-helicity determined by a
      structure prediction method that combines conformational filtering [S. Vajda,
      (1993) Journal of Molecular Biology, Vol. 229, pp. 125-145], and a Monte Carlo
      simulation [J. Figge et al. (1993) Protein Science, Vol. 2, pp. 155-164]. For the
      set of 11 peptides we find a correlation of 0.84 between the predicted [theta]222
      values and the corresponding values observed by CD spectroscopy in a high
      concentration of TFE (p < 0.01). Although we generally find a good correlation at
      high TFE concentration between observed and predicted alpha-helicity, there are
      several peptides that do not follow the predicted behavior. An analysis of the
      TFE titration curves in one such case revealed that TFE can induce a sharp
      transition from a partial beta-sheet conformation to an alpha-helical
      conformation as the TFE concentration is increased above a critical value.

PMID- 8756517
TI  - Biomolecular structure prediction at a low resolution using a neural network and
      the double-iterated Kalman filter technique.
AB  - We report the application of an integrated computational approach for
      biomolecular structure determination at a low resolution. In particular, a neural
      network is trained to predict the spatial proximity of C-alpha atoms that are
      less than a given threshold apart, whereas a Kalman filter algorithm is employed
      to outline the biomolecular fold, with a constraints set that includes these
      pairwise atomic distances, and the distances and angles that define the structure
      as it is known from the protein's sequence. The results for Crambin demonstrate
      that this integrated approach is useful for molecular structure prediction at a
      low resolution and may also complement existing experimental distance data for a
      protein structure determination.

PMID- 8756518
TI  - Changes in the polyelectrolyte-amphiphile interaction due to helix-coil
      transition induced by specific counterions or variations in temperature.
AB  - For the system kappa-carrageenan/amitriptyline it is shown that the degree of
      binding of amitriptyline is closely related to the carrageenan conformation as
      regulated by the counterions (Na+ or K+). The adsorption becomes much more
      pronounced when the carrageenan molecule is in the helix form (counterion K+)
      than when it has a coil conformation (counterion Na+). Furthermore, for the
      helical state the adsorption becomes strongly cooperative. It is also shown
      experimentally that the release from the adsorbed state has a conversion
      temperature at about 42 degrees C (helix-coil transition). The effect is also
      related to the linear charge density. For iota-carrageenan with a higher charge
      density the adsorption is strong and cooperative both in the presence of Na+ and
      K+ ions.

PMID- 8756519
TI  - Modeling the structure of the combining site of an antisweet taste ligand
      monoclonal antibody NC10.14.
AB  - We report the predicted combining site structure of the monoclonal antibody
      fragment, NC10.14, which is specific for the superpotent sweetener, N-(p
      cyanophenyl-N'-(diphenylmethyl) guanidine acetic acid, using computer-aided
      molecular modeling and experimental methods, such as fluorescence spectroscopy
      and circular dichroism. This is the first computer-aided modeling study on a
      lambda-chain antibody fragment. We have also identified the amino acids that are
      involved in ligand binding. Aromatic residues, L:91(W), L:96(W), and H:100G(Y)
      are predicted to make van der Waals contacts with the p-cyanophenyl moiety of the
      ligand. Residue H:56(K) is predicted to provide a counterion for the acetic acid
      moiety, and H:50(E) provides the negatively charged potential for interaction
      with the positive guanidinium group. We also make a comparison of the binding
      site architecture of NC10.14 with that of a related monoclonal antibody fragment
      NC6.8.

PMID- 8756520
TI  - A molecular builder for carbohydrates: application to polysaccharides and complex
      carbohydrates.
AB  - A new procedure (POLYS) for producing three-dimensional structures of
      polysaccharides and complex carbohydrates is described. This employs a builder
      concept combining a database of monosaccharide structures with a database
      containing information on populations of independent neighboring glycosidic
      linkages in disaccharide fragments. The computer program is written in C, and it
      can cope with both the complexity and the diversity of carbohydrates and the
      unique topological features arising from multiple branching. A simple ASCII
      syntax was developed for describing the primary structures in accordance with
      IUPAC nomenclature. The translation of the primary structure is made through the
      combined use of a lexical analyzer and a command interpreter. In this way the
      program can be considered as a compiler of primary structures of carbohydrates.
      However, it also generates secondary and tertiary structures in the form of
      Cartesian coordinates in formats used by most molecular mechanics programs and
      packages. In our laboratory POLYS was exhaustively tested on standard
      homopolysaccharide systems such as cellulose and mannan and found to work very
      well. We now report the ease of use and the efficiency of the molecular builder
      in applications to more complex carbohydrate systems. These include the
      structural exploration of a pentaantennary oligosaccharide having 135 residues,
      the complex family of pectic polysaccharides including the organization and
      distribution of side chains (arabinan, arabinogalactan, and galactan) on the
      rhamnogalacturonan backbone.

PMID- 8756521
TI  - A systematic analysis of average molecular weights and gelation conditions for
      branched immune complexes: the interaction between a multivalent antigen with
      distinct epitopes and many different types of bivalent antibodies.
AB  - A systematic model, based on standard equilibrium expressions and probability
      theory, is presented to calculate average molecular weights and gelation
      conditions for the immune system consisting of a single type of antigens with
      three (or more) different epitopes and three (or more) types of bivalent
      antibodies. Molecular weights Mn, Mw, Mz, and any other higher average molecular
      weights of formed branched antigen-antibody complexes in such an immune system
      are calculated directly without determining the whole distribution. The
      conditions for the formation of gel complexes also can be determined by this
      model.

PMID- 8756522
TI  - Low-resolution docking: prediction of complexes for underdetermined structures.
AB  - One of the most fundamental questions concerning ligand-receptor interaction is
      whether such a process of intermolecular association is generally determined by
      local structural elements of the participating molecules, or whether there are
      also large-scale motifs in molecule structures that facilitate complex formation.
      From the point of view of practical docking computations, the elaborate character
      of local structural details in ligand-receptor interaction creates a large number
      of false-positive matches, which interfere with determination of the best fit.
      Another significant obstacle in protein docking is the problem of structural data
      inaccuracy (poor structure resolution, conformational changes upon complex
      formation, etc.). Our study [Vakser (1995) Protein Eng., 8, 371-377], based on
      ultralow (approximately 7 A resolution) representation of molecular structures,
      allowes to average all high-resolution structural details, and still predict most
      of the structural features of the ligand-receptor complex. The approach
      dramatically improves the signal-to-noise ratio in determination of the best fit,
      and moves the structure inaccuracy tolerance to the range of the macrostructure.
      In the present paper, we describe a further validation of the main principles of
      this approach and a detailed analysis of the low-resolution docking results. This
      includes clustering of ligand positions around the receptor molecule and cross
      validation of ligands and receptors from different complexes. We also discuss the
      important implications of the approach to the multiple-minima problem and a
      possible role of different structural elements in the recognition mechanism.

PMID- 8756523
TI  - Threshold hydrophobicity dictates helical conformations of peptides in membrane
      environments.

PMID- 8756524
TI  - Dopamine and prolactin--an imperfect duo in circadian rhythmicity.

PMID- 8756525
TI  - Dopaminergic neurons of periventricular and arcuate nuclei of pseudopregnant
      rats: semicircadian rhythm in Fos-related antigens immunoreactivities and in
      dopamine concentration.
AB  - The activity of the A14 and A12 hypothalamic dopaminergic (DAergic) neurons were
      characterized throughout a day of pseudopregnancy to establish their relationship
      to the generation of PRL surges during that time. Double-label
      immunocytochemistry was performed using fos-related antigens as markers of
      neuronal activity, and tyrosine hydroxylase antibody to identify DAergic neurons
      of the periventricular nucleus and the arcuate nucleus (ARN). Dopamine
      concentrations were measured with HPLC with electrochemical detection from
      micropunched samples to approximate synthetic activities of A14 and A12 neurons.
      Serum PRL levels were determined by RIA. On the fifth and sixth day of
      pseudopregnancy, five rats/time point were killed at 1100 h, 1300 h, 1500 h, 1800
      h, 2100 h, 2400 h, 0300 h, and 0600 h. When the serum PRL was low, the incidence
      of fos-related antigens/tyrosine hydroxylase double-labeled neurons was high, and
      it decreased twice a day by 1500 and 0300 h in the periventricular nucleus,
      rostral ARN, dorsomedial subpopulation of the middle ARN, and in the caudal ARN,
      corresponding to the initiation of PRL surges. Concentrations of DA were high in
      these areas, and decreased before PRL surges in agreement with the
      immunocytochemical data. These findings suggest a semicircadian rhythm in the
      activities of A14 and A12 neurons which, in concert with PRL releasing factors,
      contribute to the generation of PRL surges in pseudopregnant animals.

PMID- 8756526
TI  - "Here the heart may give a useful lesson to the head".

PMID- 8756527
TI  - Corticotropin-releasing hormone receptor expression and functional coupling in
      neonatal cardiac myocytes and AT-1 cells.
AB  - CRH is the principal mediator of the stress response in mammals. In addition to
      pituitary and central nervous system effects, peripheral effects of CRH have been
      observed involving the immune and cardiovascular systems. Two CRH receptor
      subtypes, CRH-R1 and CRH-R2, have been cloned and show significant amino acid
      homology (69%), but differ in their tissue distribution. CRH-R1 is expressed
      predominantly in the brain and pituitary, whereas the CRH-R2 subtype is highly
      expressed in heart and skeletal muscle. To investigate the role of CRH in cardiac
      signaling, we analyzed the effect of CRH on freshly isolated neonatal rat
      cardiomyocytes and murine atrial cardiomyocyte tumor cells, AT-1, which express
      CRH-R2 messenger RNA. We show that stimulation of these cells with CRH and the
      CRH-related peptides, sauvagine from frog and urotensin I from fish, elicits
      large increases in the intracellular level of cAMP. This stimulation is
      transient, reaching a maximum in 5-15 min in neonatal cardiomyocytes and in 2-4
      min in AT-1 cells, followed by a rapid decline. We show that stimulation of AT-1
      cells by these peptides is specific for CRH receptors, as the CRH antagonist,
      alpha-helical CRH-(9-41) inhibits cAMP increases. Furthermore, we show that CRH,
      sauvagine, and urotensin I stimulations are dose dependent in both neonatal
      cardiomyocytes and AT-1 cells. Sauvagine and urotensin I are more potent than CRH
      at stimulating an increase in intracellular cAMP in neonatal cardiomyocytes (EC50
      = 1.74, 2.61, 6.42 nM, respectively) and AT-1 cells (EC50 = 16.2, 15.8, and 149
      nM, respectively). This rank order is consistent with that previously
      demonstrated in CRH-R2-transfected HEK293 cells and parallels the in vivo
      vasodilatory activity of these peptides. In summary, this is the first evidence
      that CRH, sauvagine, and urotensin I act directly on cardiac myocytes to
      stimulate increases in intracellular cAMP, presumably through CRH-R2. In
      addition, these results indicate that cardiac myocytes may be an informative in
      vitro model to investigate the effects of CRH and its role in the cardiovascular
      response to stress.

PMID- 8756528
TI  - Effects of central administration of highly selective opioid mu-, delta- and
      kappa-receptor agonists on plasma luteinizing hormone (LH), prolactin, and the
      estrogen-induced LH surge in ovariectomized ewes.
AB  - A reduction in endogenous opioid inhibition (disinhibition) of GnRH secretion is
      thought to be permissive for the preovulatory GnRH/LH surge. There are no
      published studies of the effects of highly specific opioid receptor agonists on
      the LH surge in any species, and the relative importance of the opioid receptor
      subtypes mu, delta and kappa in the mechanism of disinhibition is unknown. In
      sheep, attempts to block the LH surge with opiates have been largely
      unsuccessful, and there is little evidence for reduced opioid inhibition during
      the GnRH/LH surge. The opioid receptor subtypes regulating PRL secretion in sheep
      are also unknown. Conscious, ovariectomized ewes with permanent third ventricular
      cannulae were injected with estradiol benzoate (EB) 50 micrograms or oil im (t =
      0 h). In this model, EB elicits a time-delayed surge in LH secretion after 13-18
      h. Jugular venous blood was sampled at half hourly intervals between-2 and 0 h
      and 10 and 26 h. From 12-20 h, infusions were made into the third ventricle of
      either the highly specific mu-agonist DAGO (10, 20 or 40 nmol/h), the delta
      agonist DPDPE (40 nmol/h), the kappa-agonist U50488 (40 nmol/h) or saline
      (vehicle). In oil-treated animals (n = 4-6), DAGO infusion at 20 and 40 nmol/h
      reduced plasma LH whereas DPDPE or U50488 had no effect. In EB-treated animals (n
      = 6), DAGO (40 nmol/h) delayed the LH surge (mean +/- SEM time to surge onset
      21.4 +/- 0.3 h vs. 14.0 +/- 0.4 h in controls, P < 0.0001). DAGO at 10 nmol/h did
      not alter surge onset and at 20 nmol/h had variable effects. DPDPE or U50488 did
      not affect LH surge timing or amplitude. All doses of DAGO increased plasma PRL,
      whereas DPDPE and U50488 had no effect. We conclude that, in ovariectomized ewes,
      activation of opioid mu-receptors, but not delta- or kappa-receptors, inhibits
      GnRH secretion, can block the estrogen-induced GnRH/LH surge and increases PRL
      secretion. The results are consistent with the disinhibition hypothesis.

PMID- 8756529
TI  - Association of 1 alpha,25-dihydroxyvitamin D3-occupied vitamin D receptors with
      cellular membrane acceptance sites.
AB  - We previously reported nongenomic activation of ROS 17/2.8 cells by vitamin D
      metabolites (1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3], 25
      hydroxyvitamin D3, 22-oxa-calcitriol, etc.). The hormone 1 alpha,25-(OH)2D3, or
      calcitriol, mediated rapid transient changes in intracellular free calcium levels
      and concomitant stimulation of inositol polyphosphate and diacylglycerol
      production. These effects resemble the mechanism of cell activation induced by
      ligands with plasma membrane (PM) receptors. As preliminary studies indicated
      that PM isolated from ROS 17/2.8 cells lacked specific binding sites for
      calcitriol alone, we studied the association between calcitriol-occupied vitamin
      D receptors (VDR) and ROS 17/2.8 cellular membranes. Saturable binding to the PM
      and the endoplasmic reticulum (ER) of calcitriol-occupied VDR was demonstrated.
      Binding of the VDR-[3H]calcitriol complex was displaceable by nonradioactive
      VDR/calcitriol, but not by the unoccupied VDR or by calcitriol alone. ER binding,
      but not PM binding, was competitively inhibited by a peptide from the VDR
      sequence recognized by an ER protein, calreticulin, and by an anticalreticulin
      antibody. The monoclonal antibody (9A7) against the VDR inhibited PM and ER
      binding of the hormone-occupied VDR. These results were substantiated by studies
      using baculovirus-expressed human VDR for binding studies with the PM and ER and
      for immunoblot analysis. We conclude that specific PM and ER sites of association
      for calcitriol-occupied VDR exist and suggest that these associations could
      participate in the nongenomic rapid actions of 1 alpha,25-(OH)2D3.

PMID- 8756530
TI  - The role of growth hormone in fetal mouse reproductive tract differentiation.
AB  - Although GH plays a key role in postnatal growth and differentiation, its role in
      fetal differentiation is not clear at the present. The aim of the present study
      was to investigate whether GH plays a role in fetal sexual differentiation, and
      we used in vitro organ culture assay of sexual differentiation to determine this.
      The results showed that anti-rGH antibody blocked Wolffian duct differentiation
      specifically in the presence of fetal testes. Exogenous GH supplemented in the
      above experiment reversed the blocking effect of anti-GH. Among the other related
      products, insulin-like growth factor I was highly effective in reversing the anti
      GH effect, insulin-like growth factor II was partially effective, but PRL was
      unable to reverse the anti-GH effect. GH itself was found to produce some
      masculinizing effect, as demonstrated by its ability to stabilize the Wolffian
      duct in female fetuses. The role of GH was further demonstrated by the
      observation that GH-immunoreactive material of the size of authentic GH was
      detected in the 18-day fetal reproductive tract, and the concentration of this
      material increased in response to progression of sexual differentiation.
      Determination of androgen-binding activity using Scatchard analysis on the cells
      isolated from the 18-day fetal reproductive tract indicated that androgen-binding
      activity increased after GH treatment of the cells. Thus, it may be concluded
      that GH influences male sexual differentiation and alters the androgen-binding
      activity of the fetal reproductive tract.

PMID- 8756531
TI  - Gonadotropin-releasing hormone regulates follicle-stimulating hormone-beta gene
      expression through an activin/follistatin autocrine or paracrine loop.
AB  - The FSH beta gene is stimulated by low frequency pulses of GnRH, but is
      unaffected or suppressed when GnRH is applied at higher frequencies or
      continuously. The current studies explored the hypothesis that GnRH frequency
      dependent regulation of FSH beta may be mediated by pituitary expression of
      activin, which stimulates FSH beta messenger RNA (mRNA), and follistatin, which
      blocks activin. Using a system of perifused male rat pituitary cells, a
      reciprocal relationship was observed between FSH beta and follistatin mRNAs in
      response to different patterns of GnRH treatment. Pulses of GnRH (5 min; 10 nM)
      applied every 60 min stimulated FSH beta mRNA 14.0-fold with no change in
      follistatin mRNA. Pulses of GnRH applied every 30 and 15 min elicited stepwise
      increases in follistatin mRNA and decreases in FSH beta mRNA, and continuous GnRH
      stimulated follistatin mRNA 4.1-fold, with no significant increase in FSH beta
      mRNA. Stimulation of FSH beta mRNA by hourly GnRH pulses (3.7-fold) was blocked
      in the presence of 30 ng/ml recombinant follistatin (0.8-fold), suggesting that
      GnRH stimulation of FSH beta mRNA requires endogenous activin. Treatment of
      plated pituitary cells with continuous GnRH for 24 h confirmed that secretion of
      follistatin protein rises (1.5-fold) coincident with follistatin mRNA (1.7-fold)
      under conditions that suppress FSH beta mRNA (9% of the control value). When male
      rats were infused through arterial cannulas for 6 h with continuous GnRH (100 nM)
      or recombinant follistatin (5 micrograms/h), continuous GnRH suppressed FSH beta
      mRNA levels to 50% of the control value, and follistatin decreased expression to
      61% of the control value. We conclude that GnRH stimulation of FSH beta mRNA is
      activin dependent, and pituitary follistatin production is a major pathway by
      which higher GnRH pulse frequencies suppress FSH beta mRNA. Changes in activin or
      follistatin tone, therefore, provide a mechanism by which LH and FSH can be
      differentially regulated by GnRH in a variety of physiological and
      pathophysiological conditions.

PMID- 8756532
TI  - Effects of glucagon and glucagon-like peptide-1-(7-36) amide on C cells from rat
      thyroid and medullary thyroid carcinoma CA-77 cell line.
AB  - Glucagon is known to stimulate calcitonin secretion by thyroid C cells over a
      wide range of concentrations, raising the possibility of its interaction with
      several types of receptors. This study was designed to characterize receptors
      that mediate the effect of glucagon on a rat C cell line (CA-77). Binding
      studies, using radiolabeled [125I]glucagon and [125I]glucagon-like peptide-1-(7
      36) amide ([125I]tGLP-1), to CA-77 plasma membranes demonstrated the presence of
      1) a glucagon receptor with a dissociation constant (Kd) of 2.3 nM and relative
      potencies for structurally related peptides as follows: glucagon > oxyntomodulin
      > > tGLP-1; and 2) a tGLP-1 receptor with a Kd of 0.33 nM and relative potencies
      as follows: tGLP-1 > oxyntomodulin > glucagon. Glucagon stimulated calcitonin
      secretion from CA-77 cells in a dose-dependent manner over 4 orders of magnitude,
      with a maximal response of 312% over the basal value and an ED50 close to 50 nM.
      tGLP-1 induced a calcitonin release over 2 orders of magnitude, with a maximal
      response of 170% over the basal value and an ED50 close to 0.2 nM. Glucagon and
      tGLP-1 stimulated cAMP production in CA-77 cells to similar maximal levels over 4
      and 2 orders of magnitude, respectively. The stimulation of cAMP production by
      glucagon at concentrations over 10 nM was suppressed by the tGLP-1 antagonist
      exendin-(9-39) amide, whereas the stimulation of calcitonin secretion was only
      partly abolished. Using a perifusion system of rat thyroid, glucagon and tGLP-1
      stimulated calcitonin secretion in a calcium-dependent manner. It is concluded
      that glucagon and tGLP-1 receptors are expressed in the rat C cell line (CA-77)
      and in the normal rat thyroid. The effects of glucagon on calcitonin secretion
      observed at high concentrations are mediated in part through interaction with
      tGLP-1 receptors and via an additional non-cAMP-mediated mechanism.

PMID- 8756533
TI  - Serum stimulation of parathyroid hormone-related peptide gene expression in ROS
      17/2.8 osteosarcoma cells through transcriptional and posttranscriptional
      mechanisms.
AB  - The gene encoding PTH-related peptide (PTHrP), a protein that plays a primary
      role in the development of humoral hypercalcemia of malignancy, is widely
      expressed in normal and neoplastic tissues. This study demonstrates that
      expression of the PTHrP gene has features of early response genes, including up
      regulation after serum repletion of serum-starved ROS 17/2.8 (rat osteosarcoma)
      cells. The PTHrP messenger RNA (mRNA) levels were induced within 30 min and
      peaked at 4 h. Elevated mRNA levels were accompanied by an increase in secreted
      PTHrP. The serum effects on PTHrP mRNA levels were blocked by actinomycin D,
      suggesting a requirement for gene transcription. Nuclear run-on assays revealed a
      3-fold increase in PTHrP gene transcription 4 h after exposure to serum.
      Deletions of the 5' flanking sequence of the rat PTHrP gene fused to the
      chloramphenicol acetyltransferase gene and transfected into ROS 17/2.8 cells
      showed that the serum-responsive region is located between -1.05 kb and -0.3 kb
      upstream of the transcription start site. PTHrP mRNA levels were also induced by
      cycloheximide, another feature common to early response genes. The PTHrP mRNA
      half-life in serum-starved cells was 56 min. Serum treatment prolonged the half
      life 2.7-fold, suggesting serum-induced stabilization of the mRNA. Insulin and
      epidermal growth factor also induced PTHrP mRNA expression in a time-dependent
      manner analogous to serum, indicating that the effects of serum may be mediated,
      at least partially, through these agents. In summary, serum up-regulated PTHrP
      mRNA expression through both transcriptional and posttranscriptional mechanisms.
      This rapid stimulation by growth factors suggests that PTHrP may contribute to
      the early cellular response after growth factor stimulation.

PMID- 8756534
TI  - Endocrine and metabolite responses to porcine growth hormone administered by
      sustained release implant for different lengths of time in male pigs.
AB  - The effects of long term administration of GH on serum concentrations of hormones
      and metabolites was investigated in intact and castrate male swine. At 10 weeks
      of age, male swine were assigned to six treatments (n = 10/group): nonimplanted
      intact and castrate males; intact males implanted for 6 weeks, from 22-28 weeks
      of age; intact males implanted for 12 weeks, from 16-28 weeks of age; and intact
      and castrate males implanted for 18 weeks, from 10-28 weeks of age. Recombinant
      porcine GH was administered with sustained release implants designed to deliver a
      dose of 4 mg/day for 6 weeks. Throughout the study, blood samples were collected,
      and serum was harvested to quantitate circulating concentrations of glucose, urea
      nitrogen, GH, insulin, insulin-like growth factor I (IGF-I), IGF-II, and PRL. The
      pattern of administered GH in the serum suggests that the presence of testes and
      prior treatment with GH influence GH clearance. Somatotropin treatment elevated
      serum concentrations of GH and increased serum levels of glucose, insulin, IGF-I,
      and IGF-II in both intact and castrate animals. However, during the prepubertal
      period of 10-16 weeks, GH-treated intact males were resistant to the diabetogenic
      actions of GH, whereas significantly increased serum levels of glucose and
      insulin occurred in GH-treated castrates during this period. Changes in serum
      levels of IGF-I throughout the study and in insulin after the first 6 weeks
      followed the pattern of circulating GH concentrations in the treated animals.
      Serum concentrations of IGF-II were increased after GH administration, but, in
      contrast to the IGF-I response, IGF-II levels remained elevated as GH
      concentrations waned in the latter portion of the implant period. The maintenance
      of higher serum levels of IGF-II may be less dependent upon GH than are insulin
      and IGF-I. Administration of GH to intact males is more efficacious in altering
      metabolites and hormones, with the exception of IGF-I, during the peripubertal
      and postpubertal periods than during the prepubertal period.

PMID- 8756535
TI  - In vivo antisense antagonism of vasoactive intestinal peptide in the
      suprachiasmatic nuclei causes aging-like changes in the estradiol-induced
      luteinizing hormone and prolactin surges.
AB  - In mammals, the suprachiasmatic nuclei (SCN) regulate the timing of LH surges.
      Recent evidence suggests that vasoactive intestinal peptide (VIP), an abundantly
      expressed neuropeptide of the SCN, communicates time of day information from the
      SCN to GnRH neurons. VIP levels in the SCN decrease with age and may be
      responsible for alterations in LH surges that become apparent in middle-aged
      rats. We wished to determine whether suppression of VIP synthesis, through
      antisense oligonucleotides (oligos) directed at the SCN, results in 1) selective
      suppression of VIP levels in the SCN and 2) aging-like changes in the secretion
      of LH and PRL. To test the specificity of antisense oligo treatment, rats were
      ovariectomized and treated with estradiol. Antisense or control random oligos
      were infused into the peri-SCN region through stereotaxically placed bilateral
      cannulas. Beginning at lights off, rats were maintained in constant dim red
      illumination throughout the remainder of the experiment. They were killed at
      specific times, brains were microdissected, and VIP concentrations in the SCN,
      paraventricular nuclei, and cortex were assayed. As a control for the specificity
      of antisense VIP treatment, we monitored the levels of arginine vasopressin in
      the SCN. To test the effects of antisense treatment on the pattern of plasma LH
      and PRL secretion, blood samples were collected from atrial catheters from 1200
      2000 h, and plasma samples were assayed for LH and PRL. The results indicate that
      the effects of antisense treatment were discrete, as they suppressed VIP
      concentrations in the SCN, but had no effect on VIP concentrations in the
      paraventricular nuclei or cortex or on arginine vasopressin concentrations in the
      SCN. Peak LH levels during the surge were delayed and attenuated in antisense
      treated animals compared to random oligo-treated control rats in a manner
      strikingly similar to that observed previously in middle-aged rats. Likewise,
      PRL, which was unaffected in middle-aged rats, was also unaffected by targeted
      suppression of VIP. In summary, our findings clearly demonstrate that antisense
      VIP oligos suppress VIP levels in the SCN and do not affect peptide
      concentrations in other regions of the brain or other neuropeptides in the SCN.
      Further, we show that suppression of a single neuropeptide in the SCN can mimic
      the effects of age on the estradiol-induced surges of LH and PRL. These data
      support a central role for suprachiasmatic VIP in the regulation of the LH surge
      and suggest that age-related perturbations in the integrity of this axis may
      account for alterations in the pattern of LH secretion observed during middle
      age.

PMID- 8756536
TI  - Growth hormone modulates insulin regulation of hepatic insulin-like growth factor
      binding protein-1 transcription.
AB  - Hepatic transcription of insulin-like growth factor-binding protein-1 (IGFBP-1)
      is enhanced in hypophysectomized (hypox) rats and can be rapidly down-regulated
      by GH administration. Here we examined the effect of insulin on IGFBP-1 messenger
      RNA abundance in hypox rats and the effects of insulin and GH on IGFBP
      1/chloramphenicol acetyltransferase (CAT) reporter plasmids transiently
      transfected into isolated hepatocytes from pituitary-intact and hypox rats.
      Unlike GH, administration of insulin to hypox rats in doses of 10 or 50
      micrograms/100 g BW had no effect on hepatic IGFBP-1 messenger RNA abundance.
      Insulin at 10(-7) M resulted in a 42.1 +/- 9.8% suppression of CAT activity in
      hepatocytes from pituitary-intact animals transfected with a CAT reporter plasmid
      containing 1671 bp of the 5'-flanking region of the rat IGFBP-1 gene. In the same
      assay, GH at a concentration of 2.3 x 10(-8) M significantly reduced CAT
      activity. In contrast, insulin had no effect on CAT activity in hepatocytes from
      hypox rats, whereas GH resulted in comparable suppression of CAT activity in
      hepatocytes from hypox rats and pituitary-intact rats, 13.6 +/- 2.3% vs. 18.2 +/-
      3.2%. Deletional analysis and mobility shift assays were used to identify the GH
      responsive regions in the IGFBP-1 gene. GH suppression of CAT activity was lost
      when the IGFBP-1 5'-flanking region was deleted down to -277 bp, whereas insulin
      suppression was retained for all but the smallest fragment of the IGFBP-1 gene.
      Mobility shift assays were used to compare nuclear extracts from sham-operated,
      hypox, and GH-treated hypox rats. When hepatic nuclear extracts from hypox rats
      were incubated with the -277 to -82 and the -556 to -368 bp fragments, retarded
      bands were apparent that were not present in the extracts from sham-operated
      rats. GH treatment of hypox rats 15 or 30 min before death completely normalized
      the retardation pattern seen with the -277 to -82 bp fragment, but did not affect
      the pattern seen with the -556 to -368 bp fragment. A 20-bp fragment
      corresponding to the previously identified insulin response element, -108 to -89
      bp, was also analyzed. An additional retarded band, not seen with nuclear
      extracts from sham-operated rats, was apparent when nuclear extracts of hypox
      rats or GH-treated hypox rats were used. These data provide the first in vitro
      evidence that GH directly regulates transcription of IGFBP-1 expression. In
      addition, our findings suggest that GH modulates insulin regulation of IGFBP-1
      transcription, possibly by altering the milieu of trans-acting factors that
      interact with both the insulin response element and distinct upstream sites.

PMID- 8756537
TI  - Proglucagon gene expression is induced by gastrin-releasing peptide in a mouse
      enteroendocrine cell line.
AB  - The proglucagon gene is expressed in a cell-specific manner in the A cells of the
      islets and the L cells of the intestine; however, the physiological factors that
      regulate proglucagon gene expression are not well understood. Although insulin
      inhibits proglucagon gene transcription in the islets, peptides that stimulate
      proglucagon gene expression have not been identified. We show here that gastrin
      releasing peptide (GRP) induces proglucagon messenger RNA transcripts in STC-1
      enteroendocrine cells. The GRP induction of proglucagon gene expression was dose
      dependent, detectable by 4 h after GRP treatment, and sustained, i.e. detectable
      after a 24-h GRP incubation. GRP also induced the transcriptional activity of rat
      proglucagon promoter-luciferase plasmids in transfected STC-1 cells. The GRP
      induction of proglucagon promoter activity was attenuated, but not eliminated,
      after deletion of 5'-flanking sequences containing the proglucagon gene cAMP
      response element (CRE). A mutation in the CRE previously shown to abrogate cAMP
      responsiveness and CRE-binding protein binding was associated with a reduction in
      the transcriptional response to GRP. The proglucagon CRE also conferred GRP
      responsiveness to a truncated proglucagon promoter in STC-1 cells. These
      observations identify GRP as a peptide activator of proglucagon gene expression
      and provide evidence linking the proglucagon gene CRE to the physiological
      control of proglucagon gene expression.

PMID- 8756538
TI  - Insulin-like growth factor I of peripheral origin acts centrally to accelerate
      the initiation of female puberty.
AB  - In several species, including humans, circulating insulin-like growth factor I
      (IGF-I) levels increase during the onset of puberty, suggesting that this peptide
      contributes to attaining sexual maturity. Because IGF-I elicits LHRH release from
      the median eminence (ME) of immature female rats in vitro, we hypothesized that
      it may represent one of the peripheral signals suspected to link somatic
      development to the LHRH-releasing system at puberty. We now present evidence in
      support of this concept. Quantitation of IGF-I messenger RNA (mRNA) levels by
      ribonuclease protection assay revealed that expression of the IGF-I gene did not
      change in the medial basal hypothalamus or preoptic area of female rats during
      peripubertal development. In contrast, the contents of both IGF-Ia and IGF-Ib
      mRNA, the two alternatively spliced forms of the IGF-I gene, increased
      significantly in the liver during the early proestrous phase of puberty. This
      change was followed by an elevation in serum IGF-I levels during the late
      proestrous phase of puberty along with a concomitant increase is serum
      gonadotropin levels. The proestrous change in serum IGF-I levels was accompanied
      by a selective increase in IGF-I receptor (IGF-IR) mRNA in the ME. Small doses of
      IGF-I (2-200 ng), administered intraventricularly, effectively induced LH release
      in both juvenile and peripubertal female rats, an increase prevented by prior
      immunoneutralization of LHRH actions. Importantly, intraventricular injections of
      IGF-I (20 ng), administered twice daily in the afternoon to immature animals,
      significantly advanced puberty. Thus, these results suggest that IGF-I of
      peripheral origin contributes to the initiation of female puberty by stimulating
      LHRH release from the hypothalamus, an effect that appears to be amplified by the
      increased synthesis of IGF-I receptors in the ME during first proestrus.

PMID- 8756539
TI  - Nitric oxide mediates interleukin-1-induced matrix degradation and basic
      fibroblast growth factor release in cultured rabbit articular chondrocytes: a
      possible mechanism of pathological neovascularization in arthritis.
AB  - Prolonged incubation with interleukin-1 beta (IL-1) induced the release of large
      amounts of NO and subsequently inhibited DNA synthesis and the biosynthesis and
      accumulation of proteoglycans in cultured rabbit articular chondrocytes (RAC). IL
      1 also inhibited DNA synthesis in bovine aortic endothelial cells (BAE). On the
      other hand, DNA synthesis in BAE cocultured with RAC was not inhibited by
      prolonged incubation with IL-1. Moreover, conditioned media from RAC incubated
      for a long period with IL-1 stimulated DNA synthesis in BAE alone. This growth
      stimulatory activity was mainly due to the release of basic fibroblast growth
      factor, a heparin-binding growth factor, into RAC culture. Gelatin zymography of
      the RAC culture medium revealed that IL-1 increased the production of matrix
      metalloproteinase-2 (MMP-2) and MMP-9. NG-Monomethyl-L-arginine, an inhibitor of
      NO synthesis, inhibited all of these actions of IL-1. These results indicate that
      NO from RAC treated with IL-1 stimulates MMPs, which, in turn, degrade the
      extracellular matrix produced by RAC, resulting in the release of large amounts
      of basic fibroblast growth factor stored in the matrix, which then stimulates
      adjacent BAE proliferation. Thus, NO produced from RAC treated with IL-1 may
      modulate angiogenesis in the synovium of arthritic patients.

PMID- 8756540
TI  - Hypokalemia decreases testosterone production in male mice by altering
      luteinizing hormone secretion.
AB  - Potassium deficiency produced by feeding mice a low potassium diet caused a
      marked decrease in plasma and testicular testosterone concentrations and a
      concomitant fall in the weight of seminal vesicles and in renal ornithine
      decarboxylase activity. All of these parameters were rapidly restored when
      potassium supply was normalized. Immunocytochemical analysis of gonadotropes and
      plasma LH values suggested that the pulsatile liberation of LH by the pituitary
      was impaired in the potassium-deficient male mice. Because the synthesis of
      testosterone in the potassium-deficient mice was stimulated by exogenous LH, hCG,
      or GnRH, one can conclude that alteration of the transcellular potassium gradient
      could affect the regulation of the hypothalamo-hypophyseal-testicular axis by
      affecting the pulsatile release of GnRH. Our results showing that the stimulation
      of LH secretion after castration was similar in control and potassium-deficient
      male mice suggest that a testicular factor(s) different from testosterone could
      be implicated in the abnormal regulation of LH secretion in potassium-deficient
      mice. We conclude that plasma potassium concentration is an important factor in
      the regulation of gonadotropin secretion and testicular functions.

PMID- 8756541
TI  - Rat uterine stromal cells: thrombin receptor and growth stimulation by thrombin.
AB  - The estrogen-stimulated maturation of the immature rat uterus is mediated by
      peptide growth factors whose expression is regulated by estradiol. We present
      evidence that thrombin is a uterine growth factor. When an immature rat is given
      a single injection of estradiol, the uterus increases 50% in wet weight within 3
      h through the imbibition of water and plasma proteins, including prothrombin.
      Tissue factor, the initiator of coagulation, is induced 3- to 4-fold over the
      same time period. Thrombin is generated in situ from prothrombin through the
      coagulation cascade. It acts as a growth factor through the proteolytically
      activated thrombin receptor. Thrombin's role as a growth factor in uterine
      stromal cells is proven by two lines of evidence: demonstrations that the
      proteolytically activated thrombin receptor is present and that cultured cells
      are stimulated to grow by thrombin. Thrombin receptor in the uterus is
      demonstrated by reverse transcription-PCR for receptor messenger RNA by specific
      [125I]peptide labeling of a membrane-bound binding protein of about 60 kDa and by
      Western blot with a thrombin receptor antipeptide antibody. Thrombin's
      effectiveness as a growth factor is shown by thrombin-stimulated growth of
      primary stromal cell cultures, with maximum stimulation at 100 nM. That the
      effect is mediated by the proteolytically activated thrombin receptor is shown by
      the inhibition of growth by hirudin, a highly specific inhibitor of thrombin; the
      absence of enhanced growth with Pro-Phe-Arg-chloromethyl ketone-thrombin, an
      active site-inhibited thrombin derivative; and the stimulation of growth by the
      thrombin receptor-activating peptide.

PMID- 8756542
TI  - Parathyroid hormone rapidly stimulates phosphate transport in perfused duodenal
      loops of chicks: lack of modulation by vitamin D metabolites.
AB  - Intestinal tissue of normal (vitamin D-replete) chicks was analyzed for
      responsiveness to PTH by the criteria of phosphate transport in perfused duodenal
      loops and binding of iodinated hormone to isolated basal lateral membranes. Using
      the N-terminal fragment of the bovine hormone [bPTH-(1-34)], the peptide agonist
      was found to stimulate phosphate transport within 4 min of perfusion (P < 0.05),
      reaching 152% of the control level after 40 min of exposure to 65 pM hormone.
      Dose-response analyses revealed an apparent optimum between 65-650 pM bPTH-(1
      34), with decreased responsiveness at 6.5 nM hormone. Perfusion of duodenal loops
      with 65 pM 1,25-dihydroxyvitamin D3[1,25-(OH)2D3] also stimulated phosphate
      transport, although a combination of both hormones did not have additive effects.
      Augmented phosphate transport mediated by bPTH-(1-34) was not attenuated by
      simultaneous perfusion with 6.5 nM 24,25-(OH)2D3, in contrast to earlier findings
      with 1,25-(OH)2D3-stimulated phosphate transport. Subcellular fractionation of
      duodena vascularly perfused with control medium or 65 pM bPTH-(1-34) for 5 min
      revealed hormone-augmented levels of 32P in lysosomal and mitochondrial fractions
      and decreased soluble 32P relative to control levels. In parallel studies, 65 pM
      1,25-(OH)2D3 resulted in qualitatively similar subcellular distributions of
      radionuclide, whereas simultaneous perfusion with 65 pM 1,25-(OH)2D3 and 6.5 nM
      24,25-(OH)2D3 abolished the increase in lysosomal 32P, but not augmented
      mitochondrial, levels. These findings suggest that lysosomes are vesicular
      phosphate carriers. Finally, preparation of isolated basal lateral membranes for
      binding studies with 125I-labeled [Nle8.18,Tyr34]bPTH-(1-34) amide indicated
      specific saturable binding with a Kd of 0.2 nM. At 1000-, 100-, and 10-fold
      excesses of unlabeled competitor, bPTH-(1-34) was 90%, 80%, and 33%,
      respectively, as effective as the analog in displacing labeled peptide. The
      combined data suggest that PTH may play a significant physiological role in
      regulating intestinal phosphate absorption.

PMID- 8756543
TI  - P2-purinoreceptor evoked changes in intracellular calcium oscillations in single
      isolated human granulosa-lutein cells.
AB  - In this study, we have demonstrated that P2-purinoreceptor agonists evoke
      oscillatory intracellular calcium ([Ca2+]i) responses in human granulosa-lutein
      cells (GLCs). Intracellular calcium was measured using microspectrofluorimetric
      techniques. ATP at concentrations of 1-100 microM increased [Ca2+]i, whereas
      neither adenosine nor AMP evoked changes in [Ca2+]i. The nonhydrolysable ATP
      analogue, ATP gamma S, also elevated [Ca2+]i with an efficacy similar to that of
      ATP, indicating that the changes in Ca2+ were not due to ATP hydrolysis, but that
      human GLCs possess functional P2-purinoreceptors. Uridine triphosphate (UTP) was
      equipotent to ATP at stimulating [Ca2+]i, and both ATP and UTP were consistently
      more effective at eliciting a response than ADP, suggesting that human GLCs
      possess the P2U class of purinergic receptors (ATP = UTP > > ADP > > AMP =
      adenosine). We have demonstrated that the purinergic agonist-induced changes in
      [Ca2+]i involve both Ca2+ influx and Ca2+ mobilization from cytosolic stores.
      Prolonged ATP treatment in Ca(2+)-free buffer (1 mM EGTA) still evokes transient
      oscillatory changes in [Ca2+]i in a pertussis toxin-insensitive manner. In Ca(2+)
      containing conditions, the sustained phase of the response was generally
      unaffected by verapamil (10 microM), suggesting that influx is not occurring
      through voltage-dependent Ca(2+)-channels. These findings are consistent with the
      hypothesis that ATP and other P2-purinergic receptor agonists elicit changes in
      [Ca2+]i in human ovarian cells and that these events are initiated by the release
      of Ca2+ from cytosolic stores, and sustained by extracellular calcium ([Ca2+]e)
      influx. This is the first time that oscillatory patterns of [Ca2+]i have been
      reported in human GLCs.

PMID- 8756544
TI  - Interleukin-8 expression and modulation in human preovulatory follicles and
      ovarian cells.
AB  - Just before the time of ovulation, the number of neutrophils increases markedly
      in the thecal layer of the leading follicle. A preovulatory rise in chemotactic
      activity for neutrophils in human follicular fluid has also been detected. We
      hypothesized that interleukin-8 (IL-8), a neutrophil chemoattractant/activating
      factor and a potent angiogenic agent, may be an important modulator of leukocyte
      chemotaxis in ovulatory function. In this regard we investigated the expression
      and modulation of IL-8 in human follicular fluid samples from patients undergoing
      in vitro fertilization-embryo transfer therapy and in ovarian stromal and
      granulosa-lutein cell cultures. The concentration of IL-8 in pre-hCG follicular
      fluid samples (n = 4) was 16 +/- 12 (mean +/- SEM) pg/ml, and that in post-hCG
      samples (n = 101) was 262 +/- 45 pg/ml (P = 0.001). In post-hCG samples, the
      concentration of IL-8 in an individual follicle correlated with the size of that
      follicle (r = 0.61; P = 0.02). We also observed a correlation between serum IL-8
      levels (22 +/- 3 pg/ml) and follicular fluid levels (303 +/- 143 pg/ml), with a
      14-fold gradient (r = 0.71; P = 0.01) in 11 patients tested for both. IL-8
      messenger RNA (mRNA) and the protein were expressed constitutively in ovarian
      stromal cell cultures, and the level was increased by IL-1 alpha and tumor
      necrosis factor-alpha in a time- and concentration-dependent manner. hCG and LH
      induced higher levels of IL-8 mRNA expression and protein production.
      Granulosalutein cells also expressed IL-8 mRNA and protein, and the levels were
      increased by IL-1 alpha and tumor necrosis factor-alpha. Importantly,
      progesterone suppressed both basal and IL-1 alpha-stimulated IL-8 expression in
      stromal and granulosa-lutein cell types. In summary, we found that IL-8 levels
      are elevated in periovulatory follicular fluid, and both granulosa-lutein and
      ovarian stromal cells express the mRNA and produce the protein. The modulation of
      IL-8 in these cell cultures by steroid and trophic hormones suggests that IL-8
      may play an important role in the physiology of ovulation, such as timely
      follicular rupture and neovascularization of the corpus luteum.

PMID- 8756545
TI  - Feeding-induced stimulation of luteinizing hormone secretion in male rhesus
      monkeys is not dependent on a rise in blood glucose concentration.
AB  - Recent studies have suggested a role for glucose availability in the central
      control of reproductive function. Various experimental paradigms have shown that
      a large pharmacological reduction in circulating or cellular glucose levels can
      suppress LH secretion, ovulation, and reproductive behavior. In contrast, states
      of undernutrition, which are also associated with a suppression of reproductive
      function, are accompanied by very mild changes in circulating glucose levels. In
      monkeys, 1 day of fasting leads to a significant suppression of LH secretion
      before any significant change in blood glucose levels, and by 2 days of fasting,
      circulating glucose levels only decrease by about 20%. Refeeding a normal meal
      after 2 days of fasting results in a restoration of euglycemia and a rapid
      stimulation of LH secretion. To test the hypothesis that physiological changes in
      glucose levels occurring during brief periods of fasting and refeeding can
      modulate LH secretion, we provided monkeys that had been fasted for 2 days with
      meals that differed in the ability to raise blood glucose levels. Meals
      consisting of mixed nutrients, carbohydrate only, or protein and fat were
      provided to monkeys through indwelling gastric cannulas. Mixed nutrient infusions
      and carbohydrate infusions caused a rise in blood glucose as well as a robust
      stimulation of LH secretion. However, protein and fat meals also stimulated LH
      secretion, even though no rise in blood glucose concentrations occurred. Thus,
      the restoration of pulsatile LH secretion when fasted animals are refed is not
      dependent on an elevation in circulating glucose levels. These results do not
      support the hypothesis that physiological changes in circulating glucose levels
      play a necessary role in mediating the changes in LH secretion that occur with
      fasting and refeeding. Alternatively, these results support the hypothesis that
      the availability of metabolizable fuels, regardless of their nature, provides a
      critical cue that regulates the central drive to the reproductive axis under
      physiological conditions of fasting and feeding.

PMID- 8756546
TI  - Identification of classical, novel, and atypical protein kinase C isoenzymes in
      the bovine parathyroid.
AB  - Because phospholipid metabolism leading to the activation of protein kinase C
      (PKC) may play a key regulatory role in the degradation and secretion of PTH, we
      examined parathyroid cell fractions for the presence of various PKC isoenzymes.
      Hydroxylapatite chromatography identified the classical PKCs, alpha and beta, but
      not gamma in parathyroid cell extracts. Western blot analysis confirmed the
      presence of PKC alpha and beta in these extracts. Of the so-called novel PKCs,
      Western blot analysis revealed the presence of only one isoenzyme, novel PKC
      epsilon in parathyroid cell soluble extracts. Western blot analysis using an
      antibody to the C-terminus of the atypical isoenzyme, PKC zeta, identified a
      protein of lower molecular weight in addition to PKC zeta. This lower molecular
      weight protein presumably represents PKC lambda, which shares a high degree of C
      terminal sequence similarity with PKC zeta. These findings suggest the
      possibility that members of all three groups of the PKC family are present and
      may play a regulatory role in the bovine parathyroid cell.

PMID- 8756547
TI  - Divergent effects of interleukin-1 beta on steroidogenesis and matrix
      metalloproteinase inhibitor expression and activity in cultured rat granulosa
      cells.
AB  - The periovulatory increase in ovarian matrix metalloproteinase inhibitor (MMPI)
      expression is regulated both in vitro and in vivo by LH, but the intermediary
      steps in this process are uncertain. The purpose of this experiment was to
      determine whether interleukin-1 beta (IL-1 beta), a known modulator of MMPI
      expression in other systems and one that is induced by LH in the ovary, is
      capable of regulating granulosa matrix metalloproteinase inhibitor expression and
      activity. Using an in vitro rat granulosa cell model, these parameters were
      assessed in response to IL-1 beta or LH administration alone or in combination.
      Granulosa cells were obtained from 24-day-old immature female rats primed with 20
      IU PMSG at 22 days of age. Cells were cultured under serum-free conditions for 24
      h at 37 C in the presence of medium (control), LH (100 ng/ml), IL-1 beta (10
      ng/ml), or LH plus IL-1 beta. MMPI activity in the conditioned medium was
      assessed using a colorimetric assay (n = 6), whereas progesterone and estrogen
      concentrations in the conditioned medium were determined by RIA (n = 6). RNA was
      isolated from the granulosa cells and assessed for Northern analysis of tissue
      inhibitor of metalloproteinase-1 (TIMP-1; n = 4), TIMP-2 (n = 3), and TIMP-3 (n =
      3) expression. When added to granulosa cells, IL-1 beta and LH each significantly
      (P < 0.05) increased MMPI activity in granulosa cell-conditioned medium above
      control values (40.9 +/- 3.0% inhibition for IL-1 beta and 67.1 +/- 5.6%
      inhibition for LH vs. 31.4 +/- 2.4% inhibition for controls). When added in
      combination, IL-1 beta had no effect on LH-stimulated inhibitor activity (67.1 +/
      5.6% inhibition vs. 69.9 +/- 5.1% inhibition for LH and LH plus IL-1 beta,
      respectively). Methylamine hydrochloride treatment revealed that the majority of
      inhibitor activity in all treatment groups was derived from TIMPs. The patterns
      of TIMP-1, TIMP-2, and TIMP-3 messenger RNA expression among the treatment groups
      paralleled the TIMP-derived inhibitor activity, in that both IL-1 beta and LH
      alone stimulated transcript expression of all three TIMPs. In addition, an
      increase in progesterone production was associated with IL-1 beta-stimulated
      (1.22-fold over control values; P = 0.0006) and LH-stimulated (9.6-fold over
      control values; P = 0.007) MMPI expression and activity. Lastly, IL-1 beta and LH
      significantly (P < 0.05) decreased estrogen production by approximately 33%
      compared to that in cultures with LH only. It is concluded from the current study
      that IL-1 beta is a mediator of MMPI expression as well as granulosa cell
      steroidogenesis, and that this cytokine has divergent actions in the presence and
      absence of LH.

PMID- 8756548
TI  - Diverse functions of aromatase: O-deethylation of 7-ethoxycoumarin.
AB  - In studying the diverse functions of aromatase we found that purified and
      reconstituted aromatase also catalyzes O-deethylation of 7-ethoxycoumarin.
      Aromatase cytochrome P450 was purified from human term placentas by monoclonal
      antiaromatase P450 antibody-Sepharose 4B column chromatography. Kinetic analysis
      of the O-deethylation of 7-ethoxycoumarin by reconstituted aromatase showed Km of
      200 microM, Vmax of 12.5 nmol.min-1.mg-1, and turnover rate of 1.06 min-1. 7
      Ethoxycoumarin competitively inhibited androstenedione aromatization, the Ki was
      180 microM. Fadrozole (CGS16949A), a specific competitive aromatase inhibitor,
      and MAb3-2C2, an antiaromatase P450 monoclonal antibody, inhibited both aromatase
      and 7-ethoxycoumarin O-deethylase activities dose responsively. The IC50 of
      Fadrozole was 33 nM for aromatase and 67 nM for 7-ethoxycoumarin O-deethylase.
      The IC50 of MAb3-2C2 was 1.1 micrograms IgG for aromatase and 4.0 micrograms IgG
      for 7-ethoxycoumarin O-deethylase. These results indicate that the two enzyme
      activities are catalyzed by the same active site of the cytochrome P450. Contrary
      to the previous postulate on the mechanism-based inactivation of microsomal
      aromatase by 4-androstene-3,6,17-trione, we found that with purified aromatase,
      both the initial 19-hydroxylase and the after lyase reactions are simultaneously
      inactivated by the steroid suicide inhibitor.

PMID- 8756549
TI  - Pre- and postnatal low protein diet affect pancreatic islet blood flow and
      insulin release in adult rats.
AB  - The pancreatic islet blood flow and insulin secretion of adult rats submitted to
      an isocaloric low protein diet (8% vs. 20%) during pre- and postnatal life were
      investigated by the nonradioactive microsphere technique. In the basal state,
      female rats chronically exposed to a low protein diet (LP) displayed a specific
      marked decrease in islet blood flow (10 +/- 2 vs. 29 +/- 5 microliters/min.g
      pancreas; P < 0.01) and overall pancreatic blood flow (P < 0.01). The plasma
      insulin level, however, was not affected. During a glucose challenge, the control
      animals enhanced their islet blood flow 2.3-fold, whereas the LP group reached
      control values with a 6-fold increase. Plasma insulin levels rose similarly in
      the control and LP animals. A third group of animals designated the recuperation
      group, exposed to a low protein diet only in utero, displayed islet blood flow
      comparable to control values, but increased basal plasma insulin (2.0 +/- 0.3 vs.
      1.2 +/- 0.1 ng/ml; P < 0.05). These data are consistent with the possibility of
      dissociation of islet blood flow and insulin release under basal conditions,
      which may not be the case after a glucose challenge. Furthermore, the low blood
      flow values in the LP group may reflect an adaptive physiological response, an
      impaired pancreatic vasculogenesis, or a dysfunction of endothelial cells.

PMID- 8756551
TI  - Regulation of messenger ribonucleic acid for corticotropin releasing hormone
      receptor in the pituitary during stress.
AB  - The mechanism regulating pituitary CRH receptors during stress was studied by
      analysis of the changes in CRH receptor messenger RNA (mRNA) and CRH binding
      after acute and repeated stress and CRH and vasopressin (VP) administration in
      intact and adrenalectomized rats. Acute stress caused time- and stress type
      dependent changes in pituitary CRH receptor expression. In situ hybridization
      studies showed biphasic changes in CRH receptor mRNA after immobilization stress
      for 1 h and decreases by 2 h (P < 0.01). Increases (P < 0.01) were seen 4 and 8 h
      after the initiation of the stress, and a return to near basal levels by 12 and
      18 h. A different pattern, with a decrease by 4 h (P < 0.01) and levels similar
      to controls after 12 and 18 h, was observed after a single ip injection of
      hypertonic saline (1.5 M NaCl). Binding autoradiography showed significant
      increases in pituitary CRH binding 4, 10, and 12 h after immobilization stress,
      but significant decreases 4, 12, and 18 h after ip hypertonic saline. In
      contrast, repeated immobilization or ip hypertonic saline for 8 or 14 days
      increased pituitary CRH receptor mRNA, and CRH binding was decreased. To
      determine the role of hypothalamic CRH and VP on these stress-induced changes,
      rats were injected for 14 days with CRH, VP, or their combination at doses
      mimicking stress levels in pituitary portal circulation (1 microgram/day sc).
      Repeated injection of CRH or VP increased CRH receptor mRNA and CRH binding (P <
      0.05). CRH receptor mRNA levels further increased after combined administration
      of CRH and VP (P < 0.01), but CRH binding showed a tendency to decrease. The role
      of glucocorticoids on CRH receptor regulation was studied by analysis of the
      effects of stress on CRH receptor mRNA and CRH binding in adrenalectomized (ADX)
      rats with and without corticosterone replacement in the drinking water. Although
      in 6-day ADX rats pituitary CRH receptor mRNA levels were markedly reduced after
      acute immobilization, glucocorticoid replacement restored the stimulatory effect
      of stress to levels observed in intact rats. Similarly, a single sc injection of
      CRH (1 microgram) decreased CRH receptor mRNA in ADX rats but not in
      glucocorticoid-replaced ADX rats. CRH binding showed the expected decrease after
      ADX and was unchanged after stress or CRH injection. The increased pituitary CRH
      receptor mRNA after stress suggests that stress-induced CRH receptor down
      regulation is due to increased receptor occupancy and internalization rather than
      to a decrease in receptor synthesis. The data suggest that increased hypothalamic
      secretion of CRH and VP mediates the delayed up-regulatory effect of stress on
      CRH receptor mRNA, and that resting levels of glucocorticoids are required for
      this effect. In addition, increased VP levels are permissive for the down
      regulation of CRH binding induced by chronic pituitary exposure to stress levels
      of CRH.

PMID- 8756550
TI  - Corticosterone selectively increases follicle-stimulating hormone beta-subunit
      messenger ribonucleic acid in primary anterior pituitary cell culture without
      affecting its half-life.
AB  - We demonstrated previously that glucocorticoids differentially affect the levels
      of the two pituitary gonadotropins, LH and FSH, both in vivo and in vitro. In
      vivo, the effect of glucocorticoids is GnRH independent, indicating a direct
      action on the gonadotrope, and it leads to selective up-regulation of the
      pituitary content of FSH and FSH beta-subunit messenger RNA (mRNA). The objective
      of the present study was to confirm the direct action of corticosterone (B) on
      FSH beta-subunit mRNA in primary anterior pituitary cell culture and to assess
      whether the selective B-induced rise in FSH beta mRNA is mediated through altered
      stability of the FSH beta transcript. Anterior pituitary glands collected from
      randomly cycling female rats were dissociated with trypsin. Cells were incubated
      at 37 C for 48 h and subsequently exposed to vehicle or B (1.7 microM) for an
      additional 42 h. At the end of the incubation, media were sampled for FSH and LH,
      cells were lysed, and total RNA was isolated for Northern blot analysis. Exposure
      to B for 42 h caused direct and selective upregulation of FSH release, FSH
      content, and FSH beta mRNA; decreased alpha-subunit mRNA; and had no significant
      effect on LH release, LH content, or LH beta mRNA. To evaluate the mRNA stability
      of the three subunits, cells were exposed to the transcription blocker
      actinomycin D (act D; 5 micrograms/ml) for an additional 6 h. The combined 6-h
      treatment with B and act D slightly, but significantly, suppressed alpha-subunit
      mRNA and did not change LH beta mRNA, confirming a long half-life of the two
      gonadotropin subunit mRNAs. In contrast, FSH beta mRNA was significantly
      suppressed by act D to the same level in vehicle- and B-treated cells. The
      posttranscriptional decay rate was examined by sampling at 0, 1, 2, 3, and 6 h
      during the 6-h act D treatment period. Decay curves for FSH beta mRNA were
      parallel in vehicle- and B-treated cells, indicating that B did not alter FSH
      beta mRNA stability. We conclude that the selective B-induced rise in FSH beta
      mRNA is mediated at the level of transcription rather than mRNA stabilization.

PMID- 8756552
TI  - Cell-specific expression of the rat secretogranin II promoter.
AB  - Secretogranin II (SgII) is a member of the granin family of secretory proteins,
      which are selectively expressed in neuroendocrine cells. As a first step in
      understanding the molecular basis for cell type-specific expression of SgII, we
      isolated a 12-kb clone from a rat genomic library that contained the entire rat
      SgII coding region, the transcription initiation site, and approximately 3 kb of
      5'-flanking region. Within 75 bp of the transcription start site (+1) we located
      a TATA box and a consensus cAMP responsive element. Within the 5'-flanking
      region, a number of potential cis-acting elements were identified, including 2
      Pit-1 binding sites, 15 E box motifs, and near-perfect matches for AP-1 and AP-2
      sites. To demonstrate cell type-specific expression the rat SgII gene, a plasmid
      containing 2.6 kb of the 5'-flanking region of the SgII gene fused to the
      luciferase reporter gene (p2774Luc) was transfected into rat pheochromocytoma PC
      12 cells, rat pituitary GH4C1 (GH) cells, human BE(2)-M17 (M17) neuroblastoma
      cells, and mouse fibroblast NIH/3T3 cells. The promoter activity was 6- to 36
      fold higher in neuroendocrine cells than in NIH/ 3T3 cells. Progressive deletions
      in the 5'-flanking region to 61 bp upstream of the start site (p223Luc) had no
      effect on promoter activity in PC-12 cells. On the other hand, a 5'-deletion in
      the SgII promoter to -1032 increased promoter activity 3.8-fold in GH cells. This
      level of expression was maintained when the SgII promoter was further truncated
      to -189, whereas truncation to -61 resulted in a 2.6-fold reduction in promoter
      activity. These results suggest that the sequence between -61 and +162 bp is
      sufficient for SgII promoter activity in PC-12 cells. However, other elements in
      the 5'-flanking region contribute to both positive and negative regulation of the
      rat SgII gene in GH cells.

PMID- 8756553
TI  - Relationship among hormonal treatments, suppression of spermatogenesis, and
      testicular protection from chemotherapy-induced damage.
AB  - To further elucidate the mechanism by which hormonal pretreatment protects the
      rat testis from damage by procarbazine, we investigated the relationship between
      the suppression of hormone levels and spermatogenesis and the recovery of
      spermatogenesis from stem spermatogonia. LBNF1 rats were implanted with capsules
      containing testosterone or testosterone plus estradiol. After hormone treatment,
      rats were injected with procarbazine, and recovery of spermatogenesis was
      assessed. Testosterone (2 cm) plus estradiol (0.5-cm) reduced serum LH levels
      causing intratesticular testosterone (ITT) to fall to 3% of control levels within
      2 weeks, but testis weights and sperm head counts were not appreciably suppressed
      until 4 weeks. Two weeks' hormone pretreatment, only slightly enhanced
      spermatogenesis recovery, but 4 weeks markedly increased it. Testosterone (2 cm)
      alone produced slower suppression of spermatogenesis and less protection from
      procarbazine than did testosterone plus estradiol implants, despite equivalent
      suppression of LH and ITT. Long testosterone implants (24-cm) partially
      maintained ITT at 14% of control despite undetectable LH levels, prevented any
      decline in sperm counts, and nearly completely abrogated the protective effect of
      the hormone treatment. Protection appeared to be best correlated with the testis
      weight reduction by hormone treatment. Thus, recovery of spermatogenesis after
      chemotherapy is dependent on the degree of suppression of spermatogenesis caused
      by the reduction of ITT levels at the time of chemotherapy and likely involves
      cells, such as the Sertoli cells, that are both androgen-responsive and affected
      by the numbers of germ cells present.

PMID- 8756554
TI  - Involvement of Raf-1 kinase and protein kinase C zeta in insulin-like growth
      factor I-induced brown adipocyte mitogenic signaling cascades: inhibition by
      cyclic adenosine 3',5'-monophosphate.
AB  - In the present study we have examined the signaling cascades involved in insulin
      like growth factor I (IGF-I)-induced mitogenesis in fetal rat brown adipocyte
      primary cultures, a model that constitutively expresses a high number of IGF-I
      receptors, where IGF-I is a complete mitogen at physiological concentrations. IGF
      I rapidly stimulated beta-chain IGF-I receptor autophosphorylation, which peaked
      at a physiological/mitogenic concentration (1.4 nM) and also stimulated tyrosine
      phosphorylation of insulin receptor substrate-1 (IRS-1). Tyrosine-phosphorylated
      IRS-1 bound and subsequently activated phosphatidylinositol 3-kinase by 3.5-fold,
      whereas the tyrosine-phosphorylated IGF-I receptor was not directly associated
      with the p85 subunit of the phosphatidylinositol 3-kinase. Moreover, mitogenic
      concentrations of IGF-I enhanced glucose transport by 2.5-fold. In addition,
      tyrosine phosphorylation of the 46- and 52-kDa SHC proteins was high in the basal
      state and doubled after IGF-I treatment, whereas IGF-I enhanced by 4-fold
      tyrosine phosphorylation of the 66-kDa SHC band. Furthermore, a 2-fold increase
      in the Ras. GTP active form was induced upon IGF-I stimulation. Downstream from
      Ras, IGF-I increased both Raf kinase and protein kinase C (PKC) zeta activities
      by 3.5-fold. (Bu)2cAMP, an inhibitor of IGF-I-induced mitogenesis in fetal brown
      adipocyte primary cultures, did not block the very early steps of the IGF-I
      induced mitogenic cascade, such as IGF-I receptor autophosphorylation, IRS-1 or
      SHC tyrosine phosphorylation, and Ras activation to its GTP active form. However,
      (Bu)2cAMP disrupted IGF-I-Raf and IGF-I-PKC zeta signaling pathways by preventing
      IGF-I-induced Raf-1 kinase and PKC zeta enzymatic activities, respectively. Our
      results show the first characterization in situ of an IGF-I mitogenic signaling
      cascade that downstream Ras diverges to the nucleus through two different
      serine/threonine kinases (Raf-1 kinase and PKC zeta) in mammalian fetal primary
      cells under physiological conditions. Both kinases represent a point of
      regulation primarily described for IGF-I-induced, cAMP-inhibited mitogenic
      pathways.

PMID- 8756555
TI  - Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma
      cell line and its contribution to calcitonin secretion.
AB  - An extracellular Ca(2+)-sensing mechanism consisting of a G protein-coupled
      receptor linked to phosphoinositide turnover and inhibition of PTH secretion, has
      recently been identified in bovine parathyroid cells. In C cells, voltage
      dependent L-type calcium channels are thought to be involved in calcium-sensing
      mechanisms, but evidence exists for additional calcium-sensing mechanisms, such
      as via a calcium-sensing receptor (CaSR). Using the human medullary C cell
      carcinoma cell line TT, which lacks L-type calcium channels, we found that Ca2+
      or cations specific for the CaSR lead to the release of calcium ions from
      intracellular stores and to an increase in calcitonin secretion. By molecular
      cloning we isolated the complete protein-coding complementary DNA of a CaSR from
      human TT cells, which are derived from a human medullary thyroid carcinoma. The
      CaSR is derived from the same CaSR gene expressed in the parathyroid gland. In
      addition, TT cells contain an alternative receptor form of CaSR, CaSRb. These
      findings provide strong evidence for the presence of a functional CaSR in the
      human C cell line TT. This receptor contributes not only to the inhibition of PTH
      secretion in the parathyroid, but also to the stimulation of calcitonin secretion
      in C cells.

PMID- 8756556
TI  - Molecular cloning and characterization of a new member of the rat placental
      prolactin (PRL) family, PRL-like protein D (PLP-D).
AB  - The rat placental PRL family consists of molecules structurally similar to PRL
      and GH, and to date, seven members have been identified. During investigation of
      pregnancy stage-specific placental factors by the differential display method, we
      obtained a complementary DNA (cDNA) fragment (199 bp) encoding a peptide
      homologous to PRL-like protein (PLP)-C. By using the 3' and 5' rapid
      amplification of cDNA ends method, a full-length cDNA was cloned and tentatively
      named PLP-D. The cDNA encoded a mature protein of 240 amino acids, including a 29
      amino acid signal sequence. PLP-D contains one putative N-glycosylation site and
      six cysteine residues that are highly conserved in the placental PRL family.
      Sequence comparison between PLP-D and other members of the placental PRL family
      showed that PLP-D is highly homologous to PLP-C (80%) and decidual PRL-related
      protein (73%). Northern blot analysis revealed that PLP-D messenger RNA (mRNA)
      first appeared at day 14 of pregnancy, and that its expression increased until
      term. In situ hybridization analysis indicated that PLP-D mRNA was specifically
      expressed in spongiotrophoblast cells and trophoblast giant cells of the
      placental junctional zone. Differentiated Rcho-1 cells also expressed PLP-D mRNA,
      whereas undifferentiated Rcho-1 cells did not.

PMID- 8756557
TI  - Insulin-like growth factor I receptor messenger expression during oogenesis in
      Xenopus laevis.
AB  - To study Xenopus insulin-like growth factor I (IGF-I) receptor messenger
      expression during oogenesis, we isolated a complementary DNA (cDNA) corresponding
      to the beta-subunit of the receptor. There is a high degree of conservation
      between the deduced polypeptide and the three mammalian sequences previously
      described for the IGF-I receptor (75% homology) even though it is lower than the
      homology among mammals themselves (95% homology). IGF-I receptor messenger RNAs
      were specifically detected by reverse transcription-PCR in oocytes, embryos, and
      adult liver and muscle. By in situ hybridization, these messenger RNAs could be
      visualized only in oocytes. Quantification showed that they accumulated from the
      previtellogenic stage until early vitellogenesis. No specific labeling could be
      detected in oocytes after stage IV of vitellogenesis. Thus, the IGF-I receptor
      messenger stock does not seem to increase further beyond this point or may even
      decrease. The long 3'-untranslated sequence (1.8 kilobases) included in the cDNA
      presents no homology with those of mammalian receptor cDNAs and could be longer,
      as no polyadenylated tail is observed. Some motifs corresponding to sequence
      described as cytoplasmic polyadenylation element or that have been described in
      unstable messengers could be observed. Moreover, a deadenylation of this RNA
      occurs in the postvitellogenic stage. These results suggest that translation
      occurred very early during oogenesis. Therefore, IGF-I receptor could play a role
      early on, during oocyte growth, in addition to its involvement in the maturation
      process.

PMID- 8756558
TI  - Regulation of soluble insulin-like growth factor-II/mannose 6-phosphate receptor
      in hepatocytes from intact and regenerating rat liver.
AB  - A soluble, circulating form of the insulin-like growth factor-II/mannose 6
      phosphate receptor has been proposed to result from proteolytic cleavage of
      intact cellular receptors. This study examines receptor release in hepatocytes
      from normal and regenerating rat liver, where receptor levels are elevated. After
      partial hepatectomy, serum receptor increased from 0.64 +/- 0.02 to 1.36 +/- 0.15
      microgram/ml at 72 h after surgery, reflected by an increase in receptor
      secretion from 18.5 +/- 3.6 ng/mg protein per 24 h in cells from sham-operated
      animals (n = 14) to 100.9 +/- 10.8 ng/mg protein per 24 h in cells from
      regenerating liver (n = 8). A wide range of protease inhibitors had little or no
      effect on soluble receptor secretion, indicating that extracellular proteolysis
      of cell surface receptor is not the major route of production in hepatocytes.
      Neither insulin-like growth factor-II nor mannose 6-phosphate altered receptor
      secretion, suggesting that neither ligand has a role in elevating receptor levels
      in liver regeneration. Inhibitors of endocytosis were examined to determine
      whether soluble receptor formation occurred during receptor recycling.
      Chloroquine, NH4Cl and monensin did not inhibit soluble receptor release, whereas
      the microtubule disrupting agents, colchicine and nocodazole, caused a dose
      related increase that was reversible by the microtubule stabilizing agent, taxol.
      This suggests that alteration of early endosome pH does not alter soluble
      receptor production, but that subsequent disruption of late endosomes may result
      in increased formation and release of soluble receptor into the culture medium.

PMID- 8756559
TI  - The insulin-like growth factor II/mannose 6-phosphate receptor is required for
      proliferin-induced angiogenesis.
AB  - Proliferin stimulates endothelial cell migration in culture and
      neovascularization in vivo. Previous studies have demonstrated that proliferin
      can bind to the insulin-like growth factor II/mannose 6-phosphate receptor, and
      that binding can be blocked by mannose 6-phosphate. We have now found that this
      receptor plays an essential role in proliferin-induced angiogenesis. Proliferin
      binding to endothelial cells is blocked by the addition of mannose 6-phosphate,
      as is the ability of both recombinant and placental-derived proliferin to
      stimulate the migration of capillary endothelial cells in vitro and to induce
      neovascularization in the rat cornea. Consistent with a direct role of this
      receptor in angiogenesis, insulin-like growth factor II, as well as a mutant form
      of insulin-like growth factor II that binds to the insulin-like growth factor
      II/mannose 6-phosphate receptor but not to the insulin-like growth factor I
      receptor, also stimulate endothelial cell migration and neovascularization.

PMID- 8756560
TI  - Hormonal dependency of neural cadherin in the binding of round spermatids to
      Sertoli cells in vitro.
AB  - The procession of round spermatids through stages VII and VIII of the rat
      spermatogenic cycle is critically dependent on testosterone (T). When
      intratesticular T levels are reduced, round spermatids appear to slough from the
      seminiferous epithelium, resulting in the disappearance of elongated spermatids.
      We hypothesized that T-dependent cell adhesion molecules are involved in Sertoli
      cell-round spermatid interactions. This study examined the hormonal regulation of
      one candidate cell adhesion molecule, N-cadherin, in vitro and its participation
      in Sertoli cell-round spermatid adhesion in coculture. Sertoli cells were
      isolated from 20-day-old Sprague-Dawley rats; treated with FSH and T, alone or in
      combination; and incubated for 48 h before determination of N-cadherin
      concentrations in Sertoli cell extracts by RIA. Both FSH and T significantly
      increased the cellular content of N-cadherin (3.7-fold), whereas FSH or T alone
      had no effect. Round spermatids were isolated from adult rats, and their adhesion
      to Sertoli cells was assessed in a 48-h coculture in the presence of FSH, T, or
      FSH plus T. Adherent round spermatids were quantitated by histological evaluation
      after staining with the periodic acid-Schiff reaction. A dose-dependent increase
      in round spermatid density (number of round spermatids bound per 10,000-microns2
      Sertoli cell culture surface area) was observed with increasing T doses (7-28
      ng/ml) in the presence of FSH (1 microgram/ml), whereas FSH and T alone at these
      doses produced no effect. T also increased the N-cadherin content of the
      cocultures in a dose-dependent manner in the presence of FSH. Addition of an N
      cadherin antiserum to the Sertoli cell-round spermatid coculture in the presence
      of FSH and T significantly (P < 0.0001) reduced round spermatid density by 65%.
      It is concluded that both the production of N-cadherin by Sertoli cells and the
      binding of round spermatids to Sertoli cells are stimulated in a synergistic
      manner by T and FSH. Furthermore, the immunoneutralization data suggest the
      active involvement of N-cadherin in round spermatid-Sertoli cell adhesion in
      vitro. N-Cadherin may be one of the factors that subserve the androgen-dependent
      process of round to elongated spermatid maturation.

PMID- 8756561
TI  - The effect of relaxin on collagen metabolism in the nonpregnant rat pubic
      symphysis: the influence of estrogen and progesterone in regulating relaxin
      activity.
AB  - The aim of this study was to examine the effects of relaxin on collagen content,
      solubility, and composition in the rat pubic symphysis. Nonpregnant, female
      Sprague-Dawley rats were bilaterally ovariectomized and either unprimed or primed
      with estrogen or progesterone alone, or a combination of estrogen and
      progesterone. One week later these animals were given increasing doses of a
      synthetic human (gene-2) relaxin (0-100 micrograms) before being killed 16 h
      later. Their pubic symphysial tissues were then removed and analyzed for collagen
      content and solubility, whereas collagen composition was determined by SDS-PAGE.
      Relaxin administration significantly increased the length (140 +/- 6%) and weight
      (170 +/- 9%) of the interpubic fibrocartilage in estrogen-primed rats (n = 15).
      At the same time, it decreased the total collagen content by 68 +/- 6%, without
      altering the proportions of collagen types, which were predominantly type I (85%)
      and type II collagen (15%). Relaxin administered alone reduced the total collagen
      content by 64 +/- 4% but had no effect on collagen solubility or composition.
      Progesterone abolished the effects of relaxin in estrogen-primed rats. It is
      concluded that relaxin has a potent effect on the amount of collagen in the rat
      pubic symphysis that is enhanced by estrogen and antagonized by progesterone. The
      changes in the extracellular matrix within the pubic symphysis induced by relaxin
      may be important in the modifications that this tissue undergoes during
      pregnancy.

PMID- 8756562
TI  - Differential regulation of the growth hormone receptor gene: effects of
      dexamethasone and estradiol.
AB  - GH receptor (GHR) expression differs during development between central and
      peripheral tissues. Peripheral GHR expression is known to be sensitive to gonadal
      and adrenal steroids, but little is known about their effects on GHR in the
      central nervous system. We have now studied the effects of estradiol (E2) or
      dexamethasone on GHR expression in rat arcuate nucleus (ARC) and hippocampus,
      using quantitative in situ hybridization. Dexamethasone, which strongly down
      regulates hepatic GHR expression, had no effect on central GHR transcript
      abundance, whereas E2 treatment, which stimulates hepatic GHR expression,
      significantly reduced ARC GHR messenger RNA (mRNA) levels. E2 also increased
      somatostatin (SS) expression significantly in both ARC and periventricular nuclei
      but did not reduce ARC GH-releasing hormone (GHRH) mRNA levels. Ovariectomy
      stimulated GHR and GHRH mRNA levels in the ARC, whereas it lowered ARC SS
      expression. E2 replacement in ovariectomized animals restored GHRH and SS mRNA
      levels to control values. Hippocampal GHR mRNA transcripts showed the same
      response to these endocrine manipulations as seen in the ARC. The induction of
      hepatic GHR expression by E2 is known to involve the transcription of an
      alternate 5' untranslated first exon, GHR1. This was readily detectable in the
      liver using a specific GHR1 probe but could not be detected in any CNS area. Our
      results show that GHR expression in the CNS is sensitive to regulation by
      peripheral steroids but that CNS and hepatic expression of GHR is differentially
      regulated by the same treatments.

PMID- 8756563
TI  - Cloning and characterization of human urocortin.

PMID- 8756564
TI  - cis-acting elements and trans-acting proteins in the transcription of chorionic
      gonadotropin/luteinizing hormone receptor gene in human choriocarcinoma cells and
      placenta.
AB  - We investigated the cis-acting elements and trans-acting proteins responsible for
      a higher basal rate of transcription of hCG/LH receptor gene in human
      choriocarcinoma JEG-3 cells compared with normal term pregnancy placenta.
      Sequential deletion of the 5'-flanking region of the gene revealed that there are
      three negative control regions (NCRs) designated NCR1 (-1457 to -1373 bp), NCR2 (
      1051 to -835 bp), and NCR3 (-480 to -184 bp), and a promoter (-184 to -1 bp).
      NCR3 was more inhibitory than the other two; nearly 60-70% of the inhibitory
      activity resides in a sequence between -480 to -276 bp, and the rest resides in
      the sequence between -276 to -184 bp. Gel mobility shift assays showed that the
      nuclear extracts from JEG-3 cells contained proteins that form three complexes
      with NCR1, two with NCR2, and six with NCR3. Many of the proteins that form the
      complexes in NCR3 are shared with the other two NCRs. Most of the proteins that
      form these complexes are less abundant in nuclear extracts from JEG-3 cells than
      in those from placenta. The JEG-3 cell nuclear extracts also contained proteins
      that form three complexes with the proximal promoter of the hCG/LH receptor gene.
      These proteins were identified as Ap2, Ap2-like I, and Sp1 from the competition
      studies with synthetic excess unlabeled Ap2, Sp1, and CTF/NF1 consensus
      oligodeoxynucleotides and/or supershift in gel mobility assays with anti-Ap2
      antibody. Although the JEG-3 cell nuclear extracts contained abundant Ap2-like
      protein I and low levels of Ap2 and Sp1 proteins, the placental nuclear extracts
      contained low levels of Ap2-like protein I and very low to nondetectable levels
      of Ap2 and Sp1 proteins. Deoxyribonuclease I footprinting revealed that the
      nuclear extracts from JEG-3 cells and placent protected the -116 to -93 bp and 
      65 to -45 bp regions in the proximal promoter of the hCG/LH receptor gene that
      contain Sp1 and Ap2 binding sites, respectively. However, the nuclear extracts
      from placenta only partially protected these regions, which is consistent with
      lower levels of proteins that bind to the proximal promoter of the gene. In
      summary, we conclude that the presence of low levels of proteins that bind to the
      NCRs and the high levels of proteins, especially Ap2-like I, that bind to the
      proximal promoter can potentially explain higher transcription of the hCG/LH
      receptor gene in JEG-3 cells compared with that in normal term pregnancy human
      placenta.

PMID- 8756565
TI  - Molecular and functional characterization of V1b vasopressin receptor in rat
      adrenal medulla.
AB  - In rat adrenal medulla, PCR experiments reveal the expression of messenger RNA
      encoding the gene for the V1b vasopressin receptor. Complementary DNA amplified
      sequences corresponded to the cloned rat pituitary V1b vasopressin receptor.
      Video microscopy experiments performed on fura-2-loaded adrenal medullary or
      adrenal glomerulosa cell primary cultures showed that vasopressin dose
      dependently mobilized intracellular calcium, suggesting that functional
      vasopressin receptors are expressed in these tissues. The use of d[D-3
      Pal]vasopressin, a specific V1b vasopressin agonist, and SR 49059, a specific V1b
      vasopressin antagonist, revealed that V1b receptors are exclusively expressed in
      adrenal medulla. Using an indirect immunological approach (plasma membrane
      localization of dopamine-beta-hydroxylase), we demonstrated that stimulation of
      rat adrenal medulla V1b receptor leads to catecholamine secretion. More
      interestingly, PCR experiments performed on rat adrenal medulla RNA revealed that
      the arginine vasopressin-encoding gene is also expressed in this tissue. In
      addition, perifusion experiments indicated that [Arg8] vasopressin is released by
      the adrenal medulla. Together, these data suggest that vasopressin may regulate
      the adrenal functions by paracrine/autocrine mechanisms involving distinct
      vasopressin receptor subtypes: V1a in the adrenal cortex and V1b in the adrenal
      medulla.

PMID- 8756566
TI  - Multimeric complex formation by the thyrotropin receptor in solubilized thyroid
      membranes.
AB  - The TSH receptor (TSHR) has a large glycosylated ectodomain comprising the amino
      terminal half of the molecule (394 of 743 residues) implicated in TSH binding, as
      well as autoantibody recognition in Graves' disease. In this study we employed
      antibodies specific for the amino-terminus (Ab1), midportion (Ab2), and carboxyl
      terminus (Ab3) of the TSHR-ectodomain, previously mapped using recombinant
      receptor proteins, to detect the natural receptor present in detergent
      solubilized porcine thyroid cell membranes via immunoblotting. Several forms of
      the receptor were detected. In reduced samples Ab1 detected full-length
      holoreceptors present in both nonglycosylated and glycoslylated forms of apparent
      molecular masses 80 and 90 kDa, respectively, as well as apparent dimeric
      nonglycosylated and dimeric glycosylated holoreceptor forms resistant to
      reduction. Also detected by Ab1 were a glycosylated amino-terminal 47- to 52-kDa
      fragment of the holoreceptor (gly alpha-subunit), reduced to 42 kDa (alpha
      subunit) by Endo F deglycosylation. Ab2 detected all of the same forms. Ab3
      detected primarily a carboxy-terminal, nonglycosylated fragment of 35 kDa (beta
      subunit). In unreduced samples, the recognition pattern was unchanged with Ab1.
      Ab2 detected monomeric and dimeric beta-subunits, as well as higher order
      complexes. The different TSHR forms present in unreduced preparations were
      resolved by ammonium sulfate precipitation, confirming their autonomy. The data
      demonstrate the presence of multiple forms of the natural TSHR. Their roles in
      TSH action and TSHR autoimmunity require further exploration.

PMID- 8756567
TI  - Characterization of the mouse DAX-1 gene reveals evolutionary conservation of a
      unique amino-terminal motif and widespread expression in mouse tissue.
AB  - The human genetic disorder adrenal hypoplasia congenita with hypogonadotropic
      hypogonadism results from mutations in the recently isolated DAX-1 gene, a member
      of the nuclear hormone receptor superfamily. To study the role of DAX-1 in
      adrenal development and activation of the hypothalamic pituitary-gonadal axis,
      animal model systems will be essential. Here, we report the isolation and
      characterization of the mouse DAX-1 gene and its tissue-specific pattern of
      expression. The mouse DAX-1 gene codes for a 472-amino acid protein, with 75%
      overall nucleotide sequence homology to its human homolog. The 3.5 amino-terminal
      repeats of a unique motif with probable DNA-binding activity have been conserved
      between mouse and human, although highest conservation in the DAX-1 peptide
      exists in the carboxy-terminal ligand-binding domain. The DAX-1 gene remains X
      linked in the mouse, consistent with its potential role in sex determination. We
      have developed a sensitive reverse transcription-PCR assay that detects DAX-1
      messenger RNA in the central nervous system, pituitary, lung, heart, spleen,
      kidney, and thymus in addition to the adrenal and testis DAX-1 expression noted
      for the human DAX-1 gene. Future studies using mouse models of altered DAX-1
      expression will be critical in defining the role of this factor in tissue- and
      development-specific gene regulation.

PMID- 8756568
TI  - The effect of hypophysectomy and growth hormone replacement on sst1 and sst2
      somatostatin receptor subtype messenger ribonucleic acids in the arcuate nucleus.
AB  - Although considerable evidence indicates that somatostatin (SRIF) exerts direct
      actions on GH-releasing hormone-containing arcuate neurons within the
      hypothalamus to modulate hypophyseal GH secretion, the underlying mechanism(s)
      remains to be elucidated. We recently demonstrated high levels of expression of
      the messenger RNAs (mRNAs) coding for two prototypic receptors of the recently
      cloned SRIF receptor (sst) family, sst1 and sst2, in the arcuate nucleus of the
      rat hypothalamus. However, information on the biological roles of these receptor
      subtypes and the factors regulating their expression is lacking. In the present
      study, we hypothesized that perturbations in GH would influence sst mRNA levels
      in cells of the arcuate nucleus in vivo. To test this hypothesis, we examined the
      effects of hypophysectomy (HPX) and HPX with GH replacement, on sst1 and sst2
      mRNA levels in the brains of adult male rats by in situ hybridization using 35S
      labeled antisense riboprobes. The number of labeled cells and the density of
      silver grains per cell were quantified using a computer-assisted image analysis
      system. Two weeks after HPX, there was a 50-60% reduction in both the number and
      labeling density of sst1 and sst2 mRNA-expressing cells in the arcuate nucleus
      compared to those in sham-operated control rats. Administration of recombinant
      human GH (200 micrograms/day for 7 days by continuous sc infusion using osmotic
      minipumps) to HPX rats augmented both the cell number (P < 0.05) and labeling
      density (P < 0.01) of sst1 mRNA in the arcuate nucleus, but did not significantly
      alter sst2 mRNA levels compared to those in HPX rats infused with H2O. There were
      no significant changes in sst1 and sst2 mRNA levels in extra-arcuate areas,
      including the cerebral cortex and medial habenula, or in suprachiasmatic, medial
      preoptic, and magnocellular preoptic nuclei after either HPX or GH replacement.
      These results indicate that the expression of both sst1 and sst2 SRIF receptor
      subtypes in brain is under the regulatory influence of pituitary hormones. They
      further suggest that GH may participate in the regulation of its own secretion by
      influencing the expression of the sst1 receptor gene on arcuate neurons. Such a
      mechanism may be important in the feedback regulation of GH secretion by the
      arcuate nucleus.

PMID- 8756569
TI  - Inverse agonism of amino-terminally truncated parathyroid hormone (PTH) and PTH
      related peptide (PTHrP) analogs revealed with constitutively active mutant
      PTH/PTHrP receptors.
AB  - Inverse agonists, ligands that suppress spontaneous receptor signaling activity,
      have been described for a growing number of G protein-coupled receptors; however,
      none have been reported for the PTH/calcitonin/secretin receptor family. We took
      advantage of the constitutive signaling activity of two mutant forms of the
      PTH/PTH-related peptide (PTHrP) receptor, recently identified in patients with
      Jansen's metaphyseal chondrodysplasia, to screen for PTH and PTHrP analogs with
      inverse agonist activity. Two antagonist peptides, [Leu11, D-Trp12]hPTHrP(7
      34)NH2 and [D-Trp12, Tyr34]bPTH-(7-34)NH2, displayed inverse agonist activity and
      reduced cAMP in COS-7 cells expressing either mutant receptor by 30-50% (EC50
      approximately 50 nM). These data demonstrate that the concept of inverse agonism
      can be extended to this distinct family of G protein-coupled receptors and their
      cognate antagonist peptide ligands. Such ligands shall be useful probes of the
      multi-state conformational equilibria proposed for these receptors and could lead
      to new approaches for treating human diseases caused by receptor activating
      mutations.

PMID- 8756570
TI  - Identification by polymerase chain reaction of the G protein-coupled receptor
      kinases expressed in the mouse gonadotropic alpha T3-1 cell line.
AB  - G protein-coupled receptor kinases (GRK 1-6) stimulate short-term desensitization
      (< 5 min) by phosphorylating G-protein coupled receptors, and also participate in
      receptor sequestration, which may relate to intermediate-term desensitization (30
      60 min). The existence of such kinases and hence a potential role for them in
      gonadotrope/GnRH receptor desensitization was investigated using the PCR to
      identify GRKs in messenger RNA (mRNA) from the mouse alpha T3-1 gonadotrope cell
      line. The 150-bp complementary DNAs amplified by PCR from the kinase catalytic
      domain were cloned and sequenced. Seventeen of 42 clones were receptor kinases
      based on high nucleotide identities of 85-100% and amino acid identities of 97
      100% with rat GRK2 and 3, and with human GRK6. Among the eight GRK3 clones was
      one differing from rat GRK3 by a single nucleotide and seven differing by six; no
      amino acid difference resulted from the nucleotide differences. Of the five GRK2
      clones, one sequence was identical with rat GRK2, but four sequences differed by
      three nucleotides and one amino acid. Among four GRK6 sequences, one showed 15
      nucleotide differences from human GRK6 (with no amino acid differences), and
      three had 16 nucleotide and one amino acid differences. For each of the three
      GRKs found, the most closely related isoform is assumed to be the mouse homolog
      of rat GRK2 and GRK3, and human GRK6, whereas the others are assumed to be
      previously undescribed isoforms or subtypes of GRK2, 3, and 6. Immunocytochemical
      staining using antibodies to GRK2, 3, and 6 confirmed their presence in alpha T3
      1 cells. The function of these GRKs in alpha T3-1 cells is unknown, but they may
      be involved in short-term desensitization of the gonadotrope/GnRH receptor or
      perhaps, more likely, the sequestration of this receptor during intermediate-term
      desensitization.

PMID- 8756571
TI  - Dietary fiber modulates intestinal proglucagon messenger ribonucleic acid and
      postprandial secretion of glucagon-like peptide-1 and insulin in rats.
AB  - Intestinal hormones stimulate more than 50% of the insulin response after oral
      glucose administration. Short chain fatty acids stimulate mucosal adaptation and
      may alter proglucagon messenger RNA and release of the insulin secretagogue,
      glucagon-like peptide-1 (GLP-1). Sprague-Dawley rats ingested a fiber-free
      elemetnal diet or an elemental diet supplemented with 30% fiber providing similar
      energy and nutrients for 14 days. The cecal and colonic short chain fatty acids
      contents were significantly higher in the 30% fiber group. Ileal proglucagon
      messenger RNA levels were significantly higher in the 30% group vs. the 0% group
      (11.47 +/- 0.87 vs. 6.52 +/- 0.87 densitometer units), respectively. Similar
      trends were seen in the colon (13.36 +/- 1.0 vs. 10.90 +/- 0.77 densitometer
      units; P = 0.07). Plasma GLP-1, insulin, and C peptide levels 30 min postoral
      glucose were significantly higher in the 30% fiber group vs. the 0% group (19.8
      +/- 1.2 vs. 15.4 +/- 1.2 pg/ml, 2.67 +/- 0.4 vs. 1.29 +/- 0.5 ng/ml, and 964.4 +/
      94.4 vs. 530.2 +/- 120.4 pM, respectively). Plasma glucose and glucagon did not
      differ between groups. A diet supplemented with fiber is able to significantly
      alter proglucagon gene expression and modulate GLP-1 and insulin secretion. These
      novel findings deepen our understanding of the beneficial role of fiber in
      improving glucose homeostasis.

PMID- 8756572
TI  - Variable hormone responsiveness of osteoblast populations isolated at different
      stages of embryogenesis and its relationship to the osteogenic lineage.
AB  - A variable response to 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] hormone treatment
      was observed for osteoblast cell populations isolated from 12- and 17-day-old
      embryonic chick calvariae. The younger embryonic cell population showed 2- and 5
      fold inductions of osteocalcin and osteopontin gene expression, respectively, and
      a 25% inhibition of collagen gene expression when treated with 1,25-(OH)2D3. In
      contrast, these same genes all displayed approximately 80% inhibition of their
      expression when the older embryonic cell populations were treated with hormone.
      The hormone response was related to the appearance of the vitamin D3 receptor
      (VDR) and the developmental state of teh two cell populations by assessing the
      numbers of cells that were immunologically labeled for two osteoblast lineage,
      stage-specific surface makers (alkaline phosphatase and SB-5, an osteocyte
      marker) and the VDR. Using the sequence of marker presentation, with VDR
      appearing first, followed by alkaline phosphatase and then SB-5, models were
      tested using logistic regression analysis to validate this order of marker
      presentation and establish that the two embryonic ages of the cell populations
      represent discrete stages of their lineage. This analysis indicated that 1,25
      (OH)2D3 treatment progressed the 12-day-old embryo cell populations along their
      lineage and that the hormone promoted the appearance of its own receptor (P <
      0.001) However, the appearance of the VDR does not appear to be a determinant in
      the variable responses of the different embryonic aged cell populations to the
      hormone. These data quantitatively establish the unique nature of osteoblast cell
      populations within their lineage progression for cells isolated from embryos of
      different ages, such that cell populations isolated from younger embryos are
      comprised of primarily presumptive or immature osteoblasts, whereas cells
      isolated from older embryos are comprised of mature osteoblasts. These data also
      demonstrate that the genomic effects of 1,25-(OH)2D3 are dependent on the
      developmental stage of the osteoblast lineage, and the stimulatory actions of the
      hormone are targeted to immature osteoblasts, whereas the effect of the hormone
      on mature osteoblasts is inhibitory.

PMID- 8756573
TI  - Formation of insulin-producing cells from pancreatic acinar AR42J cells by
      hepatocyte growth factor.
AB  - Pancreatic AR42J cells are derived from acinar cells and express both exocrine
      and neuroendocrine properties. We have recently shown that these cells convert
      into insulin-producing cells in vitro after treatment with activin A and
      betacellulin. Here, we investigated the effect of hepatocyte growth factor (HGF)
      in those cells. When AR42J cells were incubated with HGF, DNA synthesis was
      attenuated, and the amylase content was reduced in a concentration-dependent
      manner. HGF-treated cells extended processes, but bundle formation was not
      observed using an antibody against tubulin. Reverse both insulin and pancreatic
      polypeptide (PP) were expressed in HGF-treated, but not naive, AR42J cells.
      Immunocytochemical analysis indicated that approximately 3% of the HGF-treated
      cells were stained with antiinsulin antibody, and some were also stained with
      anti-PP antibody. When AR42J cells were exposed to a combination of activin A and
      HGF, cells extended longer processes, and over 10% of them were stained with
      antiinsulin antibody. In these cells, messenger RNAs for insulin, PP, glucose
      transporter 2, and glucokinase, but not those for glucagon or somatostatin, were
      expressed. A subclone of AR42J cells, AR42J-B13, was obtained. Most of the AR42J
      B13 cells converted to insulin-producing cells after the incubation with activin
      A and HGF. Insulin secretion was augmented by tolbutamide, depolarizing
      concentrations of potassium, carbachol, and glucagon-like peptide-1 in these
      cells. These results indicate that HGF reduces the acinar cell-like property of
      AR42J cells and converts them into insulin-producing cells. The effect of HGF was
      markedly enhanced by activin A.

PMID- 8756574
TI  - Regulation of cellular rabbit growth hormone (GH) receptor and GH-binding protein
      generation in vitro.
AB  - In rabbits and probably in man, GH-binding protein (GHBP) is generated from
      proteolysis of GH receptor (GHR). The present study describes the modulation of
      spontaneous release of GHBP into the culture medium in relation to cellular GH
      receptor (GHR) in Chinese hamster ovary cells transfected with rabbit GHR
      complementary DNA. Secretion of GHBP (approximately 50K protein) from these cells
      was dependent on time, percentage of FCS, temperature, and protein synthesis.
      GHBP was detected in the medium at 30 min, and a linear increase was observed
      over the next 4 h. GHBP release was reduced by low incubation temperature,
      suggesting that GHBP cleavage is an energy-requiring mechanism. N-Ethylmaleimide
      (500 microM for 30 min at 30 C) markedly increased GHBP secretion, matched by a
      corresponding decrease in GHR. However, the lack of effect of N-ethyl-maleimide
      observed at 4 C further confirms the temperature dependence of GHBP release. We
      have attempted to characterize the GHBP release protease with a number of
      recognized protease inhibitors. Benzamidine (10 mM) was the only protease
      inhibitor that reduced GHBP release; however, it also reduced the cellular GHR
      level. Cycloheximide (20 micrograms/ml) caused a parallel disappearance of
      cellular GHR and secreted GHBP with a half-life of about 50 min, but increased
      GHR messenger RNA expression (superinduction). Indeed, 4 h after removal of
      cycloheximide, GHR and GHBP were increased by 181% and 369%, respectively,
      compared to the control value. In summary, Chinese hamster ovary cells expressing
      rabbit GHR provide a useful cellular model system for studies on the mechanism of
      GHBP generation from GHR and its physiological importance.

PMID- 8756575
TI  - In search of the cellular site of growth hormone (GH)-binding protein cleavage
      from the rabbit GH receptor.
AB  - Transfection of Chinese hamster ovary cells with rabbit GH receptor (GHR)
      complementary DNA resulted in high expression of cellular GHR as well as markedly
      time- and temperature-dependent secretion of soluble GH-binding protein (GHBP)
      into the culture medium. In the present study, these cells were used as an in
      vitro model system to examine GHBP secretion in relation to GHR internalization,
      degradation, recycling, and biosynthesis. Incubation for 20 h with the
      lysosomotropic agents NH4Cl and monensin inhibited GH internalization and reduced
      cell surface GHR, whereas no significant effect on the level of secreted GHBP was
      observed. Cytochalasin B, a microfilament-disrupting agent, reduced the GHR
      level, but GHBP was not affected. Colchicine, a microfilament depolymerization
      agent, had no effect on the GHR level; however, it stimulated GHBP secretion
      approximately 2-fold. Brefeldin A (5 micrograms/ml), a transport blocker,
      incubated for 15-180 min resulted in a time-dependent decline in GHR, whereas no
      significant modulation effect on GHBP was apparent. The capacity of these cells
      to synthesize and incorporate GHR at the plasma membrane in relation to the
      generation of soluble GHBP was obtained by destruction of cell surface GHR by
      mild trypsinization and subsequently monitoring the rate of recovered GHR and
      GHBP. The rate of reappearance of GHR and GHBP was rapid, being observed within 1
      h, whereas full recovery occurred within 2 and 3 h, respectively. The recovery
      was completely blocked by cycloheximide and brefeldin A. NH4Cl and monensin
      reduced GHR restoration by about 50%, but the recovery of GHBP was not affected.
      These data emphasize the importance of lysosomes and vesicular traffic in the
      regulation of secreted GHBP that might be derived from the internalized GHR and
      may provide insight into a better understanding of the cleavage process of GHBP
      from GHR.

PMID- 8756576
TI  - Regulation of aldosterone in the 7-day-old rat.
AB  - Little is known about mineralocorticoid regulation in the neonate. Here,
      adrenocortical function in 7-day-old Sprague-Dawley rats was studied by measuring
      the effects of angiotensin II (Ang II) and ACTH on serum aldosterone (ALDO),
      corticosterone, and cytochrome P-450 ALDO synthetase and 11 beta-hydroxylase
      messenger RNA (mRNA) levels with and without dexamethasone (DEX) treatment. In
      the absence of DEX, serum ALDO was unchanged after 5 micrograms/kg, but increased
      2- to 12-fold after 50 micrograms/kg, Ang II and 9- to 36-fold after 5 U/kg ACTH.
      After 4 days of exposure to exogenous ACTH, basal and Ang II-stimulated ALDO were
      markedly decreased. Basal plasma corticosterone was near or below the assay
      detection limit and did not change after Ang II, but increased significantly
      after ACTH administration. After treatment with 200 micrograms/kg DEX, basal
      serum ALDO fell to below the assay detection limit at 1 h, the responses to 50
      micrograms/kg Ang II were attenuated at 1 and 4 h and were undetectable at 18 h.
      Preincubation of 7-day-old dispersed adrenal glomerulosa cells with 100 nM DEX
      for 2 h did not decrease basal or stimulated ALDO production. In situ
      hybridization studies revealed that cytochrome P-450 ALDO synthetase mRNA was
      confined to the subcapsular zona glomerulosa, whereas cytochrome P-450 11 beta
      hydroxylase mRNA was present only in the zona fasciculata-reticularis. DEX caused
      a time-dependent decrease in P-450 ALDO synthetase mRNA (91 +/- 3%, 77 +/- 6%, 60
      +/- 13%, and 38 +/- 19% of the control value at 1, 4, 8, and 16 h, respectively),
      an effect that was not prevented by ACTH replacement. Only minimal decreases in P
      450 11 beta-hydroxylase mRNA levels were observed 18 h after DEX treatment.
      Hence, the sensitivity of ALDO responses to Ang II in the 7-day-old rat was
      markedly reduced in vivo, but not in vitro. In addition, DEX markedly reduced
      ALDO secretion, an effect that was associated with a decrease in cytochrome P-450
      ALDO synthetase mRNA.

PMID- 8756577
TI  - The extragenomic action of progesterone on human spermatozoa: evidence for a
      ubiquitous response that is rapidly down-regulated.
AB  - Image analysis techniques have been used to demonstrate that progesterone induces
      a rapid calcium transient in the acrosomal domain of greater than 90% of human
      spermatozoa (n = 2354). These results are at variance with previous reports,
      suggesting that progesterone receptors are only expressed on a small
      subpopulation of these cells, by virtue of their ability to bind fluorescent
      probes incorporating progesterone 3- (O-carboxymethyl) oxime conjugated to BSA.
      In the present study, we could confirm that such probes only bound to a small
      proportion of human spermatozoa (3.01 +/- 0.29%; n = 7557) although 91.79 +/-
      1.8% of the same sperm populations exhibited a calcium transient in response to
      progesterone. These results indicate that the binding of labeled progesterone
      conjugates to human spermatozoa does not reflect the size of the progesterone
      responsive population; the response elicited by this steroid is essentially
      ubiquitous. Progesterone action was shown to involve an influx of extracellular
      calcium via mechanisms that did not involve voltage sensitive- or second
      messenger operated-channels, phospholipase C, or G proteins. Despite previous
      evidence suggesting that progesterone action might involve a GABAA
      receptor/chloride channel, neither GABA nor the GABA agonist muscimol had any
      effect on intracellular calcium concentrations in human spermatozoa or influenced
      their functional competence. The only factor that disrupted the responses of
      human spermatozoa to progesterone was this steroid itself. Progesterone exposure
      induced a prolonged period of refractoriness to further stimulation that
      influenced the capacity of these cells to generate calcium transients, and their
      ability to exhibit a biological response to changes in intracellular calcium.
      There are implications in these results for our understanding of the extragenomic
      action of progesterone on human spermatozoa and the clinical manipulation of this
      system for the assessment and suppression of human sperm function.

PMID- 8756578
TI  - The expression of cytosolic phospholipase A2 and prostaglandin endoperoxide
      synthase in ovine maternal uterine and fetal tissues during late gestation and
      labor.
AB  - Gene expression of cytosolic phospholipase A2 (cPLA2) and prostaglandin
      endoperoxide synthase (PGHS) 1 and 2 was studied in ovine maternal uterine and
      fetal tissues during glucocorticoid induced premature labor and spontaneous labor
      and compared with gestational age matched controls not in labor. Northern blot
      analysis demonstrated that the messenger RNA (mRNA) abundance of cPLA2 and PGHS
      2, but not PGHS-1, increased significantly in the endometrium during both
      glucocorticoid induced premature labor and spontaneous labor. Protein levels of
      the two enzymes measured by Western blot analyses were also elevated in the
      endometrium during glucocorticoid induced premature labor. cPLA2 mRNA was
      detected in the myometrium, but no difference was observed between ewes in labor
      and their gestational age matched controls not in labor. While the level of PGHS
      2 mRNA was below detection in the myometrium with the methods used, the enzyme
      protein for PGHS-2 in the myometrium was significantly increased in both
      glucocorticoid induced premature labor and spontaneous labor. Using
      immunocytochemical methods, PGHS-2 enzyme protein was identified in the
      endometrial gland epithelial cells and myometrial cells. PGHS-2 mRNA was also
      detected in the ovine fetal cotyledons in which no differences for PGHS-2 mRNA
      existed between tissues collected from ewes in labor and ewes not in labor. In
      contrast, there were no detectable signals for cPLA2 or PGHS-2 mRNA in either
      amnion or chorion. We conclude that the ovine endometrium and myometrium, but not
      fetal membranes, are important tissue sites of prostaglandin biosynthesis
      involved in the process of ovine parturition.

PMID- 8756579
TI  - The ovine pars tuberalis secretes a factor(s) that regulates gene expression in
      both lactotropic and nonlactotropic pituitary cells.
AB  - The purpose of this study was to determine whether the cells of the ovine pars
      tuberalis (PT) secrete a factor(s) that can influence the activity of cells in
      the pars distalis (PD). By Northern blotting of total RNA isolated from PD cells
      that had been stimulated in the presence of cycloheximide (10 micrograms/ml), PT
      cell-conditioned medium was shown to induce a significant increase in the
      expression of the early response gene, c-fos, above both PD cell-conditioned and
      nonconditioned medium control levels (P < 0.05). Although forskolin (5 microM)
      induced a weak increase in c-fos expression in PD cells, the effect of PT medium
      conditioned in the presence of forskolin enhanced this expression more than
      additively (P < 0.05); furthermore, this effect was reversed by melatonin. These
      results are consistent with the release of a factor(s) from the PT, which for
      simplicity we have called tuberalin. This factor was released from PT cells in a
      time-dependent and cycloheximide-sensitive manner and was resistant to heating at
      100 C for 10 min. Tuberalin activity could be size-fractionated using molecular
      size cut-off filters to produce activity in both the 1- to 10-kDa and more than
      10-kDa size ranges. The activities in both of these fractions were sensitive to
      trypsin degradation and, therefore, appeared to be peptidergic. However, it was
      not clarified whether the biological activities were due to one or two
      components. Tuberalin also induced c-fos expression in other cell types,
      including GH3 and NIH3T3 cells. Dual labelling of PD cells by in situ
      hybridization using riboprobes for c-fos and PRL demonstrated that both the less
      than and more than 10-kDa fractions of tuberalin activated c-fos expression in
      some, but not all, lactotrophs in PD cell cultures, suggesting that a primary
      function of the PT is to regulate the activity of lactotrophs. This was supported
      further by enhanced secretion of PRL from PD cells in the presence of either PT
      conditioned medium or PT cells in coculture. In addition, PT-conditioned medium
      was found to increase c-fos in a second cell type, which did not hybridize
      positively for PRL, indicating the existence of other endocrine interactions
      between the PT and PD.

PMID- 8756580
TI  - Dual expression of p80 type I and p68 type II interleukin-I receptors on anterior
      pituitary cells synthesizing growth hormone.
AB  - Interleukin-1 alpha (IL-1 alpha) and IL-1 beta bind to either the p80 type I IL-1
      receptor (IL-1RI) or the p68 type II IL-1R (IL-1RII) on both T and B lymphocytes.
      We and others have previously shown that the anterior pituitary gland also has
      specific high affinity binding sites for IL-1 alpha (Kd = approximately 1 nM) and
      expresses transcripts for both isoforms of the IL-1R. However, the identity of
      cells in the anterior pituitary gland that express the IL-1R and whether
      different populations of adenohypophyseal cells express different isoforms of the
      IL-1R remain unknown. Here we have used a combination of immunohistochemistry and
      histochemistry to localize IL-1RI and IL-1RII to specific target cells in the
      mouse anterior pituitary gland. Perfusion-fixed, paraffin-embedded sections of
      anterior pituitary gland were immunolabeled with well characterized monoclonal
      antibodies to either IL-1RI or IL-1RII and counterstained using a modified
      Gomori's method to document acidophils and basophils. Immunolabeling demonstrated
      that both IL-1RI and IL-1RII were abundantly expressed on a single population of
      anterior pituitary gland cells and that these cells could be classified on the
      basis of histochemical staining as a subpopulation of acidophils. The
      distribution, morphology, and proportion of cells immunolabeled for IL-1RI and IL
      1RII were consistent with GH-synthesizing cells. To confirm this hypothesis, a
      modified indirect avidin-biotin complex, sequential peroxidase/alkaline
      phosphatase technique was used to label anterior pituitary gland cells with
      antibodies to IL-1RI followed by antibodies to IL-1RII, GH, PRL, or ACTH. The IL
      1RI-positive cells predominately coexpressed IL-1RII and GH, but very little, if
      any, PRL or ACTH. These data establish that the predominant cell population in
      the murine anterior pituitary gland that constitutively expresses IL-1R stain as
      acidophils histochemically, is round to oval with dense granular cytoplasm and
      eccentric nuclei, synthesizes GH, and simultaneously expresses IL-1RI and IL-1RII
      isoforms.

PMID- 8756582
TI  - Agonist-dependent regulation of cloned human somatostatin receptor types 1-5
      (hSSTR1-5): subtype selective internalization or upregulation.
AB  - Agonist regulation of somatostatin receptors (SSTRs) was investigated in stable
      CHO-K1 cells individually expressing the 5 human (h) SSTR subtypes. hSSTR 2,3,4,
      and 5 displayed rapid agonist-dependent internalization of [125I] LTT SST-28
      ligand in a time- and temperature-dependent manner over 60 min. Maximum
      internalization of radioligand occurred with hSSTR3 (78%) followed by hSSTR5
      (66%), hSSTR4 (29%) and hSSTR2 (20%). In contrast, hSSTR1 displayed virtually no
      internalization. Prolonged agonist treatment led to differential upregulation of
      some of the SSTRs. After 22 h, hSSTR1 was upregulated at the membrane by 110%,
      hSSTR2 and hSSTR4 by 26% and 22% respectively, whereas hSSTR3 and hSSTR5 showed
      little change. Agonist-induced recruitment of hSSTR1 to the membrane was
      confirmed by immunocytochemistry with hSSTR1 antibodies. These results show that
      SST regulates all 5 hSSTRs by differential subtype selective internalization or
      upregulation. Subtype selectivity for internalization and upregulation is
      inversely related.

PMID- 8756581
TI  - Constitutive nuclear localization of Janus kinases 1 and 2.
AB  - Both GH and the GH receptor have been reported to undergo rapid nuclear
      translocation. Janus kinases (JAK) 1 and 2 have been implicated in GH receptor
      signaling, and both of these kinases are phosphorylated by GH stimulation. In
      this report, we have investigated the subcellular distribution of JAK1 and JAK2.
      Both JAK1 and JAK2 exhibit a nucleocytoplasmic distribution by
      immunocytochemistry in unstimulated serum deprived CHO cells stably transfected
      with rat GH receptor complementary DNA (cDNA). The nucleocytoplasmic localization
      of JAK2 was verified by immunogold electron microscopy in both rat liver
      hepatocytes and CHO cells stably transfected with rat GH receptor cDNA.
      Nucleocytoplasmic localization of JAK2 was also verified by transient tranfection
      of CHO cells with a Haemophilus influenzae haemagglutinin (HA) epitope tagged
      JAK2 expression plasmid and subsequent localization of HA immunoreactivity.
      Western blot analysis of purified nuclear extracts revealed the presence of
      immunoreactive JAK1 at 130 kDa and immunoreactive JAK2 at 128 kDa. No change in
      the nuclear content of JAK1 or JAK2 was observed upon ligand stimulation of GH
      receptor cDNA transfected cells with 100 nM human GH for 5, 10, 15, 30, or 60
      min. GH stimulation caused, however, the appearance of tyrosine phosphorylated 42
      and 44-kDa proteins as well as tyrosine phosphorylated JAK2 in the nucleus. The
      constitutive nuclear localization of the Janus Kinases is suggestive of a novel
      nuclear role for JAK family members, in addition to their described cytosolic
      function and presents an interesting challenge to the subcellular site of hormone
      action.

PMID- 8756583
TI  - Intercellular communication: relative importance of cellular adhesion and
      paracrine signaling to hormonal gene expression.
AB  - Although there is a consensus that a cell's microenvironment can have a dramatic
      influence on its ability to express a particular gene, the relative contribution
      of physical interaction (cell to cell adhesion) and paracrine signaling to this
      phenomenon has been difficult to discern. Here, we addressed this problem in
      mammotropes by making "real-time" measurements of prolactin (PRL) gene expression
      followed by immunocytochemistry (for post facto identification of a neighbor's
      phenotype). Our results show that it is the nature (phenotype) rather than the
      physical presence of a neighboring cell that dictates the degree to which the PRL
      gene is expressed.

PMID- 8756584
TI  - The beta 3-adrenergic receptor inhibits insulin-stimulated leptin secretion from
      isolated rat adipocytes.
AB  - Various model systems have been used to study the expression of the recently
      cloned ob gene, leptin. Here we report that freshly isolated rat white adipocytes
      incubated with insulin release leptin in a rapid and concentration-dependent
      manner (EC50 of 0.221 +/- .075 nM). Insulin-stimulated leptin release could be
      detected as early as 30 min and a maximal 2-3 fold effect was produced by 10 nM
      insulin. The effect of insulin was completely blocked by simultaneous activation
      of cAMP-dependent protein kinase. Using the activation of lipolysis as an index
      of cAMP-dependent protein kinase activity, we show that inhibition of leptin
      release by norepinephrine or the selective beta 3-adrenergic receptor agonist,
      CL316,243, occurred in parallel to activation of cAMP-dependent protein kinase.
      In addition, beta 1- and beta 2-adrenergic receptor antagonists did not impair
      the ability of norepinephrine or CL316,243 to inhibit leptin release from the
      adipocytes. These findings suggest that the beta 3-adrenergic receptor plays a
      central role in regulating the release of leptin from the adipocyte.

PMID- 8756585
TI  - The human osteoclast precursor circulates in the monocyte fraction.
AB  - The osteoclast is known to be formed by fusion of circulating mononuclear
      precursor cells of haematopoietic origin. The precise nature of these circulating
      cells and, in particular, their relation to monocytes is unknown. We have
      developed an in vitro system of human osteoclast formation whereby human
      monocytes [CD14, CD11a, CD11b and HLA-DR positive, and tartrate-resistant acid
      phosphatase (TRAP), calcitonin receptor (CTR), vitronectin receptor (VNR)
      negative] were isolated and cocultured for up to 21 days with UMR106 rat
      osteoblast-like cells or ST2 mouse preadipocytic bone marrow stromal cells in the
      presence of 1 alpha, 25 dihydroxyvitamin D3 (1,25(OH)2D3) and macrophage colony
      stimulating factor (M-CSF). Numerous TRAP, VNR and CTR positive multinucleated
      cells, capable of extensive lacunar bone resorption, formed in these cocultures;
      the absolute requirements for this to occur were contact with the above bone
      stromal cells, 1,25(OH)2D3, and M-CSF. These results show that the human
      mononuclear osteoclast precursor circulates in the monocyte fraction and exhibits
      a monocyte phenotype, acquiring osteoclast phenotypic features in the process of
      differentiation into mature functional osteoclasts.

PMID- 8756586
TI  - Growth hormone (GH) therapy markedly increases the motility of spermatozoa and
      the concentration of insulin-like growth factor-I in seminal vesicle fluid in the
      male GH-deficient dwarf rat.
AB  - There is increasing evidence for an important role of the somatotropic axis in
      male reproductive function. We investigated the effect of recombinant bovine GH
      (rbGH) treatment for 21 days on semen characteristics in post-pubertal GH
      deficient dwarf (dw/dw) rats. Male dw/dw rats at an age of 75-80 days were
      divided into two groups (n = 10 per group) and injected twice per day with either
      rbGH (2 micrograms/g/day) or saline. While the concentration (96.4 +/- 51.3 x
      10(6) per ml) and morphology of spermatozoa (spermatozoa with normal morphology
      73.5 +/- 6.3%) in the dw/dw rat were within the normal range, the motility of
      spermatozoa was very low (27.5 +/- 11.7%), establishing a state of sub-fertility.
      The rbGH treatment markedly increased (p < 0.01) motility of spermatozoa (44.5 +/
      10.7%) but did not change the concentration (144 +/- 80.3 x 10(6) per ml) and
      morphology (spermatozoa with normal morphology 79.5 +/- 6.0%). The rbGH treatment
      also significantly increased the concentration of insulin-like growth factor-I
      (IGF-I) in blood plasma (control 389.1 +/- 65 ng/ml, rbGH 813.9 ng/ml, p < 0.001)
      and in seminal vesicle fluid (control 11.3 +/- 3.0 ng/ml, rbGH 16.1 +/- 5.4
      ng/ml, p < 0.05). We conclude that rbGH therapy markedly increases motility of
      spermatozoa in sub-fertile male GH-deficient dw/dw rats. Thus, GH therapy may
      offer considerable potential for the treatment of impaired male reproductive
      performance.

PMID- 8756587
TI  - Cloning of Brassica napus CTP: phosphocholine cytidylyltransferase cDNAs by
      complementation in a yeast cct mutant.
AB  - CTP:phosphocholine cytidylyltransferase is a rate-limiting enzyme in biosynthesis
      of phosphatidylcholine in plant cells. We have isolated four cDNAs for the
      cytidylyltransferase from a root cDNA library of Brassica napus by
      complementation in a yeast cct mutant. The deduced amino-acid sequences of the B.
      napus enzymes resembled rat and yeast enzymes in the central domain. Although all
      cytidylyltransferases ever cloned from B. napus and other organisms were
      predicted to be structurally hydrophilic, the yeast cct mutant transformed with
      one of the B. napus cDNA clones restored the cytidylyltransferase activity in the
      microsomal fraction as well as in the soluble fraction. These results are
      consistent with a recent view that yeast cells contained a machinery for
      targeting the yeast cytidylyltransferase to membranes, and may indicate that the
      B. napus enzyme was compatible with the machinery.

PMID- 8756588
TI  - Isolation and characterization of a microspore-specific gene from tobacco.
AB  - The characterization of a gene with a unique microspore-specific expression
      pattern is reported. Isolated microspores from tobacco were used to synthesize a
      cDNA library. Clones that did not hybridize to leaf cDNA were further
      characterized by northern analysis. One clone proved to be a microspore-specific
      cDNA, representing a transcript of 650 nt. The corresponding gene, NTM19
      (Nicotiana tabacum microspore-specific), was isolated and its sequence analysed.
      The gene encodes a protein of 10.8 kDa with a pI of 6.92 and a putative signal
      sequence at the N-terminus. A localization study revealed a unique spatial and
      temporal distribution. The transcript was only detected in the unicellular
      microspore. No hybridization signals were observed in other pollen developmental
      stages, nor in the surrounding anther tissues or other vegetative tissues of the
      plant. Therefore it can be concluded that NTM19 is a gene with a highly
      microspore-specific character according to both localization and stage of
      expression. Southern blot analysis demonstrated the presence of a small gene
      family. The occurrence of TNM19 was investigated in a range of closely and
      distantly related species and was found to be present in other solanaceous
      species, including the ancestors of tobacco and in a monocot species.

PMID- 8756589
TI  - Molecular characterisation of an S-like RNase of Nicotiana alata that is induced
      by phosphate starvation.
AB  - We characterised a cDNA encoding an S-like RNase (RNase NE) from the styles of
      the self-incompatible plant, Nicotiana alata. RNase NE is 86% identical to an
      extracellular RNase from tomato cell cultures, RNase LE. DNA hybridisation
      experiments indicate that there are ca. 5-6 sequences related to RNase NE in the
      N. alata genome and that RNase NE is not linked to the self-incompatibility (S)
      locus. RNase NE is expressed in the styles, petals and immature anthers but not
      in the vegetative tissues of N. alata plants under normal growth conditions.
      Under phosphate-limited conditions, RNase NE expression is induced in roots but
      not leaves of N. alata. A transcript hybridising to RNase NE is also induced in
      N. plumbaginifolia cell cultures in response to phosphate starvation. RNase NE is
      likely to play a role in the response of N. alata to phosphate limitation,
      possibly by scavenging phosphate from sources of RNA in the root environment. We
      also discuss the evolutionary relationships between the S- and S-like RNase genes
      in plants.

PMID- 8756590
TI  - A major cysteine proteinase, EPB, in germinating barley seeds: structure of two
      intronless genes and regulation of expression.
AB  - The barley cysteine proteinase B (EPB) is the main protease responsible for the
      degradation of endosperm storage proteins providing nitrogenous nutrients to
      support the growth of young seedlings. The expression of this enzyme is induced
      in the germinating seeds by the phytohormone, gibberellin, and suppressed by
      another phytohormone, abscisic acid. In situ hybridization experiments indicate
      that EPB is expressed in the scutellar epithelium within 24 h of seed
      germination, but the aleurone tissue surrounding the starchy endosperm eventually
      becomes the main tissue expressing this enzyme. The EPB gene family of barley
      consists of two very similar genes, EPB1 and EPB2, both of which have been mapped
      to chromosome 3. The sequences of EPB1 and EPB2 match with the two previously
      published cDNA clones indicating that both genes are expressed. Interestingly,
      neither of these genes contain any introns, a rare phenomenon in which all
      members of a small gene family are active intronless genes. Sequence comparison
      indicates that the barley EPB family can be classified as cathepsin L-like
      endopeptidases and is most closely related to two legume cysteine proteinases
      (Phaseolus vulgaris EP-C1 and Vigna mungo SHEP) which are also involved in seed
      storage protein degradation. The promoters of EPB1 and EPB2 have been linked to
      the coding sequence of a reporter gene, GUS, encoding beta-glucuronidase, and
      introduced into barley aleurone cells using the particle bombardment method.
      Transient expression studies indicate that EPB promoters are sufficient to confer
      the hormonal regulation of these genes.

PMID- 8756591
TI  - Characterization of hsr201 and hsr515, two tobacco genes preferentially expressed
      during the hypersensitive reaction provoked by phytopathogenic bacteria.
AB  - During an incompatible interaction between tobacco and the bacterial
      phytopathogen Pseudomonas solanacearum, 2 classes of genes, the so-called hsr
      (hypersensitivity-related) genes, activated preferentially during the
      hypersensitive reaction, and the str (sensitivity-related) genes, expressed
      strongly during compatible and incompatible interactions, have been identified.
      In this report, two hsr cDNA clones, hsr515 and hsr201, as well as their
      expression patterns are presented. Hsr515 was found to encode a P450
      monooxygenase and is most similar to the ripening-related avocado gene CYP71A1
      (40.6% amino acid identity). Hsr201 presents 58.6% amino acid identity with
      pTom36, a tomato gene expressed during fruit maturation. The putative functions
      of the hsr gene products appear to be quite diverse and their characteristics of
      activation were found to be very conserved: accumulation of the corresponding
      mRNAs primarily in leaf areas in contact with the avirulent P. solanacearum
      strain or with a Pseudomonas fluorescens strain containing the hrpZ gene encoding
      a necrotizing polypeptide, harpin and absence of expression during normal plant
      development. Our results also suggest that, in a tobacco line expressing NahG, a
      lower level of salicylic acid, a compound associated with systemic acquired
      resistance, and also possibly involved in the development of necrotic lesions
      characteristic of the HR, does not affect the hsr gene expression.

PMID- 8756592
TI  - Characterization of a strawberry gene for auxin-binding protein, and its
      expression in insect cells.
AB  - A gene encoding an auxin-binding protein (ABP1) was isolated from strawberry by
      screening a genomic library with an ABP1 cDNA from maize. It resembles ABP1 genes
      from other sources both in structure (four introns) and in the high level of
      homology of the deduced amino acid sequence of the mature protein encoded in
      exons 2-5. Exon 1, encoding mainly the non-conserved signal peptide, was
      identified by a reverse transcriptase-polymerase chain reaction (RT-PCR)
      technique. Northern analysis indicated that ABP1 transcript levels were low
      during fruit development, but transcripts were detected by RT PCR at all stages
      of receptacle swelling (auxin-dependent) and ripening (inhibited by auxin),
      consistent with a role for ABP1 in auxin perception. Southern blot analysis
      indicated a small ABP1 gene family in octoploid cultivated strawberry, and four
      genes were identified by comparison of genomic and cDNA sequences. RT PCR was
      used to amplify the complete coding region for cloning as cDNA, and a recombinant
      baculovirus was constructed for the expression of strawberry ABP1 in insect
      cells. The coding region contains three consensus glycosylation sites, and
      multiple bands representing a range of glycoforms of the protein were detected on
      western blots of insect cell extracts. Only a single band was observed in
      extracts of tunicamycin-treated cells, and glycosylated protein yielded a unique
      N-terminal amino acid sequence, allowing determination of the signal peptide
      cleavage site.

PMID- 8756593
TI  - Small G proteins of two green algae are localized to exocytic compartments and to
      flagella.
AB  - The Ypt/Rab proteins are small GTPases, which belong to the Ras superfamily and
      have been shown to be involved in endo- and exocytosis in mammalian cells and
      yeast. Using affinity-purified antibodies specific for four Ypt proteins, namely
      Ypt1p, Ypt4p, Ypt5p and Ypt6p, of the multicellular green alga Volvox carteri
      (YptVp) and its close unicellular relative Chlamydomonas reinhardtii (YptCp), we
      examined the abundance of the corresponding antigens during the asexual life
      cycle of Volvox, and their intracellular localization. The YptV proteins were
      found in all stages throughout the asexual life cycle and are tightly associated
      with intracellular membranes. Indirect immunofluorescence revealed that YptV4p,
      YptV5p and YptV6p are present in perinuclear regions of the cell, indicating an
      association with the Golgi region. Golgi localization of YptV4p and YptV6p in
      Volvox was confirmed by immunogold electron microscopy. In contrast, we found
      Ypt1p associated with the contractile vacuole in both V. carteri and C.
      reinhardtii. Furthermore, the YptV proteins were also detected along the entire
      length of the flagella of somatic Volvox cells. This flagellar location was
      substantiated by western blot analysis of extracts prepared from isolated
      flagella of both algae. While localization to exocytic compartments is in
      agreement with the established Ypt/Rab function in intracellular vesicle
      transport of eukaryotic cells, presence in the algal flagellum is the first hint
      of a possible role for small G proteins also in motility organelles.

PMID- 8756595
TI  - The maize caffeic acid O-methyltransferase gene promoter is active in transgenic
      tobacco and maize plant tissues.
AB  - The pattern of expression directed by the promoter of the maize caffeic acid O
      methyltransferase (COMT) gene was studied by histochemical and fluorometric beta
      glucuronidase (GUS) analysis in transgenic maize and tobacco plants. The COMT
      promoter directs GUS expression to the xylem and the other tissues undergoing
      lignification, and it responds to wounding and to elicitors. In transgenic maize
      plants, expression of GUS corresponds to the pattern of expression of the
      endogenous COMT gene as determined by northern analysis and in situ
      hybridization. The pattern in transgenic tobacco plants clearly shows that the
      maize promoter sequence is recognized by tobacco transcriptional factors, in
      spite of the anatomical differences and the evolutionary distance between these
      two species. The results suggest that the most significant promoter signals that
      induce the specific expression of the lignin COMT are conserved in different
      species.

PMID- 8756594
TI  - The BARE-1 retrotransposon is transcribed in barley from an LTR promoter active
      in transient assays.
AB  - The BARE-1 retrotransposon occurs in more than 10(4) copies in the barley genome.
      The element is bounded by long terminal repeats (LTRs, 1829 bp) containing motifs
      typical of retrotransposon promoters. These, the presence of predicted priming
      sites for reverse transcription, and the high conservation for all key functional
      domains of the coding region suggest that copies within the genome could be
      active retrotransposons. In view of this, we looked for transcription of BARE-1
      within barley tissues and examined the promoter function of the BARE-1 LTR. We
      demonstrate here that BARE-1-like elements are transcribed in barley tissues, and
      that the transcripts begin within the BARE-1 LTR downstream of TATA boxes. The
      LTR can drive expression of reporter genes in transiently transformed barley
      protoplasts. This is dependent on the presence of a TATA box functional in planta
      as well. Furthermore, we identify regions within the LTR responsible for
      expression within protoplasts by deletion analyses of LTR-luc constructs.
      Similarities between promoter regulatory motifs and regions of the LTR were
      identified by comparisons to sequence libraries. The activity of the LTR as a
      promoter, combined with the abundance of BARE-1 in the genome, suggests that BARE
      1 may retain the potential for propagation in the barley genome.

PMID- 8756596
TI  - Cloning, molecular and functional characterization of Arabidopsis thaliana allene
      oxide synthase (CYP 74), the first enzyme of the octadecanoid pathway to
      jasmonates.
AB  - Allene oxide synthase, an enzyme of the octadecanoid pathway to jasmonates, was
      cloned from Arabidopsis thaliana as a full-length cDNA encoding a polypeptide of
      517 amino acids with a calculated molecular mass of 58705 Da. From the sequence,
      an N-terminal transit peptide of 21 amino acids resembling chloroplast transit
      peptides was deduced. Three out of four invariant amino acid residues of
      cytochrome P450 heme-binding domains are conserved and properly positioned in the
      enzyme coding region, including the heme-accepting cysteine (Cys-470). Southern
      analysis indicated in A. thaliana only one allene oxide synthase gene to be
      present. While transcript levels were rapidly and transiently induced after
      wounding of the leaves, allene oxide synthase activity remained nearly constant
      at a low level of ca. 0.8 nkat per mg of protein. The cDNA encoding A. thaliana
      allene oxide synthase was highly expressed in bacteria giving rise to a
      polypeptide of the calculated molecular mass. The protein was enzymatically
      active, and verification of the reaction products by GC-MS showed that it was
      capable of utilizing not only 13-hydroperoxylinolenic acid (13-hydroperoxy-9(Z),
      11(E), 15(Z)-octadecatrienoic acid), but also 13-hydroperoxylinoleic acid (13
      hydroperoxy-9(Z), 11(E)-octadecadienoic acid) as substrate. The data suggest
      parallel pathways to jasmonates from linolenic acid or linoleic acid in A.
      thaliana.

PMID- 8756597
TI  - Function of 3' non-coding sequences and stop codon usage in expression of the
      chloroplast psaB gene in Chlamydomonas reinhardtii.
AB  - The rate of mRNA decay is an important step in the control of gene expression in
      prokaryotes, eukaryotes and cellular organelles. Factors that determine the rate
      of mRNA decay in chloroplasts are not well understood. Chloroplast mRNAs
      typically contain an inverted repeat sequence within the 3' untranslated region
      that can potentially fold into a stem-loop structure. These stem-loop structures
      have been suggested to stabilize the mRNA by preventing degradation by
      exonuclease activity, although such a function in vivo has not been clearly
      established. Secondary structures within the translation reading frame may also
      determine the inherent stability of an mRNA. To test the function of the inverted
      repeat structures in chloroplast mRNA stability mutants were constructed in the
      psaB gene that eliminated the 3' flanking sequences of psaB or extended the open
      reading frame into the 3' inverted repeat. The mutant psaB genes were introduced
      into the chloroplast genome of Chlamydomonas reinhardtii. Mutants lacking the 3'
      stem-loop exhibited a 75% reduction in the level of psaB mRNA. The accumulation
      of photosystem I complexes was also decreased by a corresponding amount
      indicating that the mRNA level is limiting to PsaB protein synthesis. Pulse-chase
      labeling of the mRNA showed that the decay rate of the psaB mRNA was
      significantly increased demonstrating that the stem-loop structure is required
      for psaB mRNA stability. When the translation reading frame was extended into the
      3' inverted repeat the mRNA level was reduced to only 2% of wild-type indicating
      that ribosome interaction with stem-loop structures destabilizes chloroplast
      mRNAs. The non-photosynthetic phenotype of the mutant with an extended reading
      frame allowed us to test whether infrequently used stop codons (UAG and UGA) can
      terminate translation in vivo. Both UAG and UGA are able to effectively terminate
      PsaB synthesis although UGA is never used in any of the Chlamydomonas chloroplast
      genes that have been sequenced.

PMID- 8756598
TI  - The Pisum sativum MAP kinase homologue (PsMAPK) rescues the Saccharomyces
      cerevisiae hog1 deletion mutant under conditions of high osmotic stress.
AB  - Previous analysis of the MAP kinase homologue from Pisum sativum (PsMAPK)
      revealed a potential MAP kinase motif homologous to that found in eukaryotic cdc2
      kinases. Sequence comparison showed a 47% identity on amino acid sequence basis
      to the Saccharomyces cerevisiae Hog1p MAP kinase involved in the osmoregulatory
      pathway. Under conditions of salt-stress aberrant morphology of a hog1 deletion
      mutant was completely restored and growth was partially restored by expression of
      the PsMAPK. This shows that PsMAPK is functionally active as a MAP kinase in S.
      cerevisiae. Comparison of PsMAPK with other kinases involved in osmosensitivity,
      showed a high degree of homology and implicates a possible role for PsMAPK in a
      P. sativum osmosensing signal transduction pathway.

PMID- 8756599
TI  - A reverse transcriptase activity in potato mitochondria.
AB  - A reverse transcriptase activity has been detected in potato mitochondria using
      special RNAs as templates: a bacterial RNA coding for neomycin phosphotransferase
      (neo pa RNA) and a Neurospora crassa mitochondrial RNA (184 nt RNA).
      Surprisingly, no exogenous primer addition was required. These RNA templates
      share a primary and secondary structure similar to the T psi CG loop of tRNAs
      that could constitute the recognition site for the enzyme. Reverse transcriptase
      activity was inhibited by ddTTP, ethidium bromide and aphidicolin, while potato
      mitochondrial DNA polymerase was not inhibited by aphidicolin indicating that
      these activities correspond to distinct enzymes. A conserved sequence of reverse
      transcriptases was detected in potato mitochondrial DNA suggesting that this
      enzyme could be mitochondrially encoded.

PMID- 8756600
TI  - Isolation of an Arabidopsis homologue of the maize homeobox Knotted-1 gene.
AB  - The shoot apical meristem (SAM) is responsible for forming most of the above
      ground portion of the plant. We sought to isolate regulatory genes expressed in
      the Arabidopsis SAM by screening a Brassica oleracea (cauliflower) meristem cDNA
      library with the homeobox fragment from the maize Knotted-1 (Kn1) gene. We
      isolated and characterized the corresponding clone, Merihb1, from Arabidopsis.
      Analysis shows that the predicted MERIHB1 protein exhibits strong homology to KN1
      and RS1 from maize, SBH1 from soybean, and KNAT1 and KNAT2 from Arabidopsis.
      Merihb1 is highly expressed in mRNA from cauliflower meristems and also
      accumulates in stem and flower mRNA. Based on the similarity of the Merihb1 and
      Kn1 sequences, expression patterns, and in situ hybridizations, we suggest that
      Merihb1 represents an Arabidopsis homologue of the maize Kn1 gene.

PMID- 8756602
TI  - Transcripts of the two NADPH protochlorophyllide oxidereductase genes PorA and
      PorB are differentially degraded in etiolated barley seedlings.
AB  - The light-dependent reduction of protochlorophyllide to chlorophyllide in higher
      plants is catalyzed by two closely related enzymes, the NADPH-Pchlide
      oxidoreductases A and B that are encoded by the nuclear genes PorA and PorB,
      respectively. The expression of the PorA gene is negatively regulated by light.
      It has formerly been reasoned that, apart from the well-studied transcriptional
      down-regulation, a post-transcriptional mechanism may exist that contributes
      markedly to the light-induced decline of PorA mRNA steady-state levels. We
      investigated the degradation kinetics of the PorA messenger after inhibiting RNA
      synthesis with cordycepin. The PorA mRNA was found to be inherently unstable. In
      contrast, the PorB mRNA was shown to be stabilized in the presence of cordycepin,
      suggesting degradation by a mechanism different from that of PorA mRNA
      degradation. The PorA messenger instability is postulated to be conferred by a
      previously described plant-specific DST element in its 3'UTR.

PMID- 8756601
TI  - A novel MADS-box gene of potato (Solanum tuberosum L.) expressed during the early
      stages of tuberization.
AB  - A potato MADS-box gene cDNA (POTM1-1) from an early tuber cDNA library has been
      isolated and characterized. The deduced amino acid sequence of POTM1-1 cDNA
      encodes 250 amino acids of a putative transcription factor containing a MADS-box
      domain and a K-box domain. These conserved domains share high homologies to those
      of flower-specific homeotic proteins, TM4 of tomato and AP1 of Arabidopsis,
      indicating that POTM1-1 gene is a homologue of the AP1 gene family. The levels of
      POTM1-1 transcripts were high in axillary buds, underground stolen tips, and
      newly formed tubers, but relatively low in mature tubers. During axillary bud
      development in a model petiole-leaf cutting system, the levels of POTM1-1
      transcripts were abundant in actively growing shoots and during the early stages
      of microtuber development. It is possible that POTM1-1 functions as a
      transcription factor that regulates plant developmental processes in a number of
      tissue types.

PMID- 8756603
TI  - Tissue-specific expression of the PAL3 promoter requires the interaction of two
      conserved cis sequences.
AB  - The bean PAL2 and PAL3 promoters confer expression in overlapping sets of tissue
      types in transgenic tobacco. The PAL3 promoter contains motifs that resemble two
      AC cis elements which are required for tissue-specific expression of the PAL2
      promoter. The functions of these motifs in the PAL3 promoter were determined by
      analysis of mutated PAL3 promoter-GUS constructs in transgenic tobacco. This
      revealed that the AC motifs are necessary for tissue-specific expression of the
      PAL3 promoter. Therefore, a key role is indicated for AC elements, which are Myb
      protein binding sites, in regulating tissue-specific expression of the bean PAL
      gene family.

PMID- 8756604
TI  - A point mutation in the gene encoding the Rubisco large subunit interferes with
      holoenzyme assembly.
AB  - Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco), a key enzyme of
      photosynthetic CO2 fixation, is composed of 8 large and 8 small subunits. The
      Rubisco-deficient Nicotiana tabacum mutant Sp25 is able to synthesize the
      peptides for both subunits but does not contain any active holoenzyme. The
      phenotype is maternally inherited and thus caused by a mutation in the
      chloroplast genome, which also encodes the Rubisco large subunit. A comparison of
      the nucleotide sequences of the large subunit gene of the Sp25 mutant with that
      of the wild-type tobacco revealed a single nucleotide change in the Sp25 mutant.
      This resulted in an amino acid substitution at Gly-322, which was replaced by
      serine.

PMID- 8756605
TI  - Characterization of eight new members of the calmodulin-like domain protein
      kinase gene family from Arabidopsis thaliana.
AB  - A family of calcium-responsive protein kinases is abundant in plant cell extracts
      but has not been identified in animals and fungi. These enzymes have a unique
      structure consisting of a protein kinase catalytic domain fused to carboxy
      terminal autoregulatory and calmodulin-like domains. In this report, we present
      the amino acid sequences for eight new Arabidopsis cDNA clones encoding isoforms
      of this enzyme. Three isoforms were expressed as fusion proteins in Escherichia
      coli and exhibited calcium-stimulated protein kinase activity. We propose CPK as
      the gene designation for this family of enzymes and describe a phylogenetic
      analysis for all known isoforms.

PMID- 8756606
TI  - Two new oleosin isoforms with altered expression patterns in seeds of the
      Arabidopsis mutant fus3.
AB  - Oleosins are proteins associated with lipid bodies mainly synthesised during seed
      development. Using a subtractive hybridisation approach two new members of the
      oleosin gene family of Arabidopsis thaliana have been isolated. The quantitative
      and temporal expression patterns of both genes are found to be affected in the
      fus3 mutant defective in late embryogenesis. This pattern is interpreted as a
      molecular marker for a mutant specific developmental change from a seed
      maturation to a germination pathway.

PMID- 8756607
TI  - Characterization of DNA sequences encoding a novel isoform of the 55 kDa B
      regulatory subunit of the type 2A protein serine/threonine phosphatase of
      Arabidopsis thaliana.
AB  - We have identified a novel gene (AtB beta) encoding a previously uncharacterized
      isoform of the B regulatory subunit of the type 2A serine/threonine protein
      phosphatase (PP2A) of Arabidopsis, and show that mRNA derived from the AtB beta
      gene accumulates in all Arabidopsis organs. In addition, we examined the
      expression of the three genes encoding the A regulatory subunit of Arabidopsis
      PP2A and show these genes are expressed in all organs as well. Taken together,
      our results suggest a myriad of PP2A subunit combinations, possibly with distinct
      substrate specificities, may occur within each Arabidopsis cell.

PMID- 8756608
TI  - Cloning of a cDNA encoding the 21.2 kDa oleosin isoform from Arabidopsis thaliana
      and a study of its expression in a mutant defective in diacylglycerol
      acyltransferase activity.
AB  - A full-length cDNA clone (pA23) of 832 bp encoding an oleosin from Arabidopsis
      thaliana was isolated by differential screening of a silique-specific cDNA
      library with probes prepared from poly(A)+ RNA isolated from developing seeds of
      wild-type (WT) Arabidopsis and from mutant AS11 with a lesion affecting
      diacylglycerol acyltransferase (DGAT) activity during embryo development. The
      encoded protein has a calculated molecular mass of 21.2 kDa, and its amino acid
      sequence shows strong sequence homology and structural similarity to other known
      oleosins. Transcription of the oleosin gene during seed development was both
      reduced and delayed in AS11 compared to WT. However, the level of oleosin protein
      did not appear to be down-regulated during seed development, and at maturity, the
      overall level of oleosin protein was similar in both WT and AS11. These findings
      indicate that regulation of oleosin gene expression is part of a highly complex,
      and co-ordinated expression of storage lipid biosynthesis and related (oleosin)
      genes during oilseed development.

PMID- 8756609
TI  - Isolation and sequence analysis of a cDNA encoding the c subunit of a vacuolar
      type H(+)-ATPase from the CAM plant Kalanchoe daigremontiana.
AB  - We report the sequence of a cDNA clone encoding the c ("16 kDa') subunit of a
      vacuolar-type H(+)-ATPase (V-ATPase) from Kalanchoe daigremontiana, a plant in
      which the cell vacuole plays a pivotal role in crassulacean acid metabolism. The
      clone, pKVA211, was isolated from a K. daigremontiana leaf cDNA library
      constructed in lambda ZAP II using a homologous PCR-generated cDNA probe for the
      V-ATPase c subunit. The KVA211 cDNA was 839 nucleotides long and included a 20 bp
      poly(A)+ tail together with a complete 495 bp coding region for a polypeptide
      with a predicted molecular mass of 16659 Da. The deduced amino acid sequence was
      highly conserved across the wide range of eukaryotes (vertebrates, invertebrates,
      fungi, plants and protozoa) in which this gene has now been identified. Sequence
      comparison of several PCR products and genomic Southern analysis indicated that
      the V-ATPase c subunit in K. daigremontiana is encoded by a small multi-gene
      family. Steady-state levels of the KVA211 mRNA were much higher in leaves than in
      roots or flowers, and expression of this transcript in leaves was shown to be
      strongly light-dependent.

PMID- 8756610
TI  - Isolation of cDNA clones of genes induced upon transfer of Chlamydomonas
      reinhardtii cells to low CO2.
AB  - Unicellular algae grow well under limiting CO2 conditions, aided by a carbon
      concentrating mechanism (CCM). In C. reinhardtii, this mechanism is inducible and
      is present only in cells grown under low CO2 conditions. We constructed a cDNA
      library from cells adapting to low CO2, and screened the library for cDNAs
      specific to low CO2-adapting cells. Six classes of low CO2-inducible clones were
      identified. One class of clone, reported here, represents a novel gene associated
      with adaptation of cells to air. A second class of clones corresponds to the air
      inducible periplasmic carbonic anhydrase I (CAH1). These clones represent genes
      that respond to the level of CO2 in the environment.

PMID- 8756611
TI  - The cyanobacterial genome contains a single copy of the ffh gene encoding a
      homologue of the 54 kDa subunit of signal recognition particle.
AB  - Cyanobacteria possess thylakoid membranes that differ in their protein
      composition from the cytoplasmic membrane. To study possible pathways of protein
      targeting to these membranes, we have investigated whether or not cyanobacteria
      have a homologue or homologues of the signal recognition particlelike chaperone
      Ffh. We have amplified a fragment of ffh by polymerase chain reaction and
      established that ffh is present as a single copy in the genomes of three
      cyanobacterial species. We have cloned and sequenced ffh from Synechococcus sp.
      PCC7942 and predict that Ffh functions as a ribonucleoprotein in cyanobacteria
      and chloroplasts.

PMID- 8756612
TI  - Immobilization of manganese peroxidase from Lentinula edodes on alkylaminated
      Emphaze AB 1 polymer for generation of Mn3+ as an oxidizing agent.
AB  - Manganese peroxidase (MnP) is secreted by white-rot fungi and participates in the
      degradation of lignin by these organisms. MnP uses H2O2 as an oxidant to oxidize
      MnII to MnIII as the manganic ion Mn3+. The Mn3+ stabilized by chelation, is a
      highly reactive nonspecific oxidant capable of oxidizing a variety of toxic
      organic compounds. Previous attempts at immobilization of MnP, purified from
      Lentinula edodes through reactive amino groups, have been hindered by the
      protein's low lysing content of only 1% and its instability above pH 6.0. As an
      alternative to amine coupling, the enzyme has now been covalently immobilized
      through its carboxyl groups, using an azlactone-functional copolymer derivatized
      with ethylenediamine and 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) as
      a coupling reagent. The immobilization reaction was performed under acidic (pH
      5.25) conditions, and 90% coupling efficiency was achieved within 2h. Net
      immobilization efficiencies, expressed as the product of protein coupling
      efficiency and enzyme activity, have been measured at > 95% within 4h. The MnP-NH
      polymer and the free soluble protein were characterized and compared for their
      pH, temperature, and storage stabilities, as well as their H2O2 dependence and
      kinetics. The tethered MnP, employed in an immobilized enzyme bioreactor for
      generation of chelated Mn3+ may have industrial applications as a nonspecific
      oxidant of organopollutants.

PMID- 8756613
TI  - Stability of invertase in reverse micelles.
AB  - The stability of invertase was studied under various conditions, including at 75
      degrees C, in presence of stabilizers (sorbitol and glycerol) at 75 degrees C,
      and in the presence of denaturants (urea and trichloroacetic acid) at 37 degrees
      C in reverse micelles. Stability of the invertase in reverse micelles was found
      to be improved over that of the enzyme in bulk aqueous solution. Sorbitol could
      enhance enzyme stability as it does in the bulk aqueous system. The stabilizing
      effect of glycerol was reduced in reverse micelles. The denaturation pattern of
      urea remains unaltered. However, the denaturation effect of trichloroacetic acid
      has been reduced in reverse micelles.

PMID- 8756614
TI  - Biotransformation of uridine monophosphate (UMP) and glucose to uridine
      diphosphate-glucose (UDPG) by Candida saitoana KCTC7249 cells.
AB  - The present study investigates the biotransformation of glucose with uridine
      monophosphate (UMP) to obtain sugar nucleotide, UDP-glucose (UDPG), by the dried
      cells of Candida saitoana KCTC7249. The biotransformation was optimized by
      varying the concentrations of substrates and phosphate ion. UDPG (24 mM) was
      biotransformed from 200 mM glucose and 37.5 mM UMP by dried cells of C. saitoana.
      The glucose yields about 64% UDP-glucose, based on UMP concentration. The
      addition of glucose-1-phosphate to the reaction mixture accelerated the formation
      of UDPG from a concentration of UMP. The structure of UDP-glucose obtained was
      determined with 13C NMR and FAB mass spectra. These results indicate that the
      yeast-dried cells could be used for the production of nucleotide sugars for donor
      molecules of complex carbohydrate synthesis.

PMID- 8756615
TI  - Activation of NF-kappaB/Rel by CD40 engagement induces the mouse germ line
      immunoglobulin Cgamma1 promoter.
AB  - Interaction between CD40 on B cells and CD40 ligand (CD40L) on T cells has been
      shown to mediate T-cell contact help for B-cell proliferation, differentiation,
      and immunoglobulin isotype switching. It has recently been shown that cross
      linking CD40 on mouse B cells induces germ line gamma1 and epsilon transcripts
      and that interleukin-4 synergizes with CD40 signaling to further induce these
      germ line transcripts. Germ line transcripts have been shown to be required for
      class switch recombination. Here we show that signaling via CD40 increases
      expression of a transiently transfected luciferase reporter plasmid driven by the
      germ line Cgamma1 promoter in M12.4.1 B-lymphoma cells. By linker-scanning
      mutation analysis of the promoter, we have identified a CD40-responsive region
      (CD40RR) which is able to confer inducibility by CD40L to a minimal c-fos
      promoter. The CD40RR contains three binding sites for NF-kappaB/Rel proteins
      which are each required for maximal induction of CD40RR activity by CD40L.
      Binding of the NF-kappaB/Rel proteins p50, p65, c-Rel, and RelB to the CD40RR is
      induced by CD40 signaling in M12.4.1 cells and in splenic B cells. Cotransfection
      of expression plasmids for p50 and p65 or p50 and RelB, but not c-Rel, into
      M12.4.1 cells transactivates the CD40RR and the germ line gamma1 promoter. These
      data demonstrate that NF-kappaB Rel proteins activated by CD40 ligation play an
      important role in induction of the germ line Cgamma1 promoter.

PMID- 8756616
TI  - Activation of vascular endothelial growth factor gene transcription by hypoxia
      inducible factor 1.
AB  - Expression of vascular endothelial growth factor (VEGF) is induced in cells
      exposed to hypoxia or ischemia. Neovascularization stimulated by VEGF occurs in
      several important clinical contexts, including myocardial ischemia, retinal
      disease, and tumor growth. Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric
      basic helix-loop-helix protein that activates transcription of the human
      erythropoietin gene in hypoxic cells. Here we demonstrate the involvement of HIF
      1 in the activation of VEGF transcription. VEGF 5'-flanking sequences mediated
      transcriptional activation of reporter gene expression in hypoxic Hep3B cells. A
      47-bp sequence located 985 to 939 bp 5' to the VEGF transcription initiation site
      mediated hypoxia-inducible reporter gene expression directed by a simian virus 40
      promoter element that was otherwise minimally responsive to hypoxia. When
      reporters containing VEGF sequences, in the context of the native VEGF or
      heterologous simian virus 40 promoter, were cotransfected with expression vectors
      encoding HIF-1alpha and HIF-1beta (ARNT [aryl hydrocarbon receptor nuclear
      translocator]), reporter gene transcription was much greater in both hypoxic and
      nonhypoxic cells than in cells transfected with the reporter alone. A HIF-1
      binding site was demonstrated in the 47-bp hypoxia response element, and a 3-bp
      substitution eliminated the ability of the element to bind HIF-1 and to activate
      transcription in response to hypoxia and/or recombinant HIF-1. Cotransfection of
      cells with an expression vector encoding a dominant negative form of HIF-1alpha
      inhibited the activation of reporter transcription in hypoxic cells in a dose
      dependent manner. VEGF mRNA was not induced by hypoxia in mutant cells that do
      not express the HIF-1beta (ARNT) subunit. These findings implicate HIF-1 in the
      activation of VEGF transcription in hypoxic cells.

PMID- 8756617
TI  - Specific DNA replication mutations affect telomere length in Saccharomyces
      cerevisiae.
AB  - To investigate the relationship between the DNA replication apparatus and the
      control of telomere length, we examined the effects of several DNA replication
      mutations on telomere length in Saccharomyces cerevisiae. We report that a
      mutation in the structural gene for the large subunit of DNA replication factor C
      (cdc44/rfc1) causes striking increases in telomere length. A similar effect is
      seen with mutations in only one other DNA replication gene: the structural gene
      for DNA polymerase alpha (cdc17/pol1) (M.J. Carson and L. Hartwell, Cell 42:249
      257, 1985). For both genes, the telomere elongation phenotype is allele specific
      and appears to correlate with the penetrance of the mutations. Furthermore,
      fluorescence-activated cell sorter analysis reveals that those alleles that cause
      elongation also exhibit a slowing of DNA replication. To determine whether
      elongation is mediated by telomerase or by slippage of the DNA polymerase, we
      created cdc17-1 mutants carrying deletions of the gene encoding the RNA component
      of telomerase (TLC1). cdc17-1 strains that would normally undergo telomere
      elongation failed to do so in the absence of telomerase activity. This result
      implies that telomere elongation in cdc17-1 mutants is mediated by the action of
      telomerase. Since DNA replication involves transfer of the nascent strand from
      polymerase alpha to replication factor C (T. Tsurimoto and B. Stillman, J. Biol.
      Chem. 266:1950-1960, 1991; T. Tsurimoto and B. Stillman, J. Biol. Chem. 266:1961
      1968, 1991; S. Waga and B. Stillman, Nature [London] 369:207-212, 1994), one
      possibility is that this step affects the regulation of telomere length.

PMID- 8756618
TI  - Activation of codependent transcription factors is required for transcriptional
      induction of the vgf gene by nerve growth factor and Ras.
AB  - Nerve growth factor (NGF) treatment of PC12 cells leads to the elaboration of a
      neuronal phenotype, including the induction of neuronally expressed genes such as
      vgf. To study vgf transcription, we have created chimeric vgf/beta-globin genes
      in which vgf promoter sequences drive the expression of the beta-globin reporter
      gene or of a chimeric beta-globin gene fused to 3' untranslated vgf gene
      sequences. We have found that the level of inducibility of the latter construct
      by NGF resembles that of the endogenous vgf gene. Using transient transfection of
      the chimeric reporter genes into PC12 cells, into PC12 subclones expressing
      activated or dominantly interfering mutant Ras proteins, and into PC12 variants
      expressing specific NGF receptor/Trk mutants, we show that transcriptional
      regulation of the vgf promoter by NGF is mediated through a Ras-dependent
      signaling pathway. By mutational analysis of the vgf promoter, we have identified
      three promoter elements involved in mediating transcriptional induction by NGF
      and Ras. In addition to the cyclic AMP-responsive element (CRE), which binds to
      ATF-1, ATF-2, and CRE-binding protein in PC12 nuclear extracts, a novel CCAAT
      element and its binding proteins were identified, which, like the CRE, is
      necessary but not sufficient for the Ras-dependent induction of the vgf gene by
      NGF. We also identify a G(S)G element unusually located between the TATA box and
      transcriptional start site, which binds the NGF- and Ras-induced transcription
      factor, NGFI-A, and amplifies the transcriptional response. Integrating data from
      studies of vgf promoter regulation and NGF signal transduction, we present a
      model for vgf gene induction in which transcriptional activation is achieved
      through the persistent, direct activation of multiple interacting transcription
      factors binding to CRE and CCAAT elements, coordinated with the delayed
      transcription factor action at a G(S)G element resulting from the induced
      expression of NGFI-A.

PMID- 8756619
TI  - Anchorage-dependent transcription of the cyclin A gene.
AB  - NIH 3T3 cells cultured in suspension fail to express cyclin A and hence cannot
      enter S phase and divide. We show that loss of cell adhesion to substratum
      abrogates cyclin A gene expression by blocking its promoter activity through the
      E2F site that mediates its cell cycle regulation in adherent cells. In suspended
      cells, G0-specific E2F complexes remain bound to the cyclin A promoter.
      Overexpression of cyclin D1 restores cyclin A transcription in suspended cells
      and rescues them from cell cycle arrest. In suspended cells, cyclin D1 and cyclin
      E accumulate normally upon serum stimulation, but their associated kinases remain
      inactive; their substrates, pRb and p107, are not hyperphosphorylated.
      Concomitantly, the cyclin-dependent kinase inhibitor, p27KIP1, is stabilized.
      Ectopic expression of p27KIP1 blocks cyclin A promoter activity through its EN
      binding site. These data suggest that the block to cyclin A transcription in
      nonadherent NIH 3T3 cells results from stabilization of p27KIP1 and subsequent
      inactivation of the specific E2F moiety required for its induction.

PMID- 8756620
TI  - TATA-box DNA binding activity and subunit composition for RNA polymerase III
      transcription factor IIIB from Xenopus laevis.
AB  - The RNA polymerase III transcription initiation factor TFIIIB contains the TATA
      box-binding protein (TBP) and polymerase III-specific TBP-associated factors
      (TAFs). Previous studies have shown that DNA oligonucleotides containing the
      consensus TATA-box sequence inhibit polymerase III transcription, implying that
      the DNA binding domain of TBP is exposed in TFIIIB. We have investigated the TATA
      box DNA binding activity of Xenopus TFIIIB, using transcription inhibition assays
      and a gel mobility shift assay. Gel shift competition assays with mutant and
      nonspecific DNAs demonstrate the specificity of the TFIIIB-TATA box DNA complex.
      The apparent dissociation constant for this protein-DNA interaction is
      approximately 0.4 nM, similar to the affinity of yeast TBP for the same sequence.
      TFIIIB transcriptional activity and TATA-box binding activity cofractionate
      during a series of four ion-exchange chromatographic steps, and reconstituted
      transcription reactions demonstrate that the TATA-box DNA-protein complex
      contains TFIIIB TAF activity. Polypeptides with apparent molecular masses of 75
      and 92 kDa are associated with TBP in this complex. These polypeptides were
      renatured after elution from sodium dodecyl sulfate-gels and tested individually
      and in combination for TFIIIB TAF activity. Recombinant TBP along with protein
      fractions containing the 75- and 92-kDa polypeptides were sufficient to
      reconstitute TFIIIB transcriptional activity and DNA binding activity, suggesting
      that Xenopus TFIIIB is composed of TBP along with these polypeptides.

PMID- 8756621
TI  - The atrial natriuretic factor promoter is a downstream target for Nkx-2.5 in the
      myocardium.
AB  - The recently described NK2 family of homeodomain proteins are key developmental
      regulators. In Drosophila melanogaster, two members of this family, bagpipe and
      tinman, are required for visceral and cardiac mesoderm formation, respectively.
      In vertebrates, tinman appears to represent a family of closely related NK2
      genes, including Nkx-2.5, that are expressed at an early stage in precardiac
      cells. Consistent with a role for Nkx-2.5 in heart development, inactivation of
      the Nkx-2.5 gene in mice causes severe cardiac malformations and embryonic
      lethality. However, little is known about the molecular action of Nkx-2.5 and its
      targets in cardiac muscle. In this paper, we report the identification and
      characterization of a functional and highly conserved Nkx-2.5 response element,
      termed the NKE, in the proximal region of the cardiac atrial natriuretic factor
      (ANF) promoter. The NKE is composed of two near-consensus NK2 binding sites that
      are each able to bind purified Nkx-2.5. The NKE is sufficient to confer cardiac
      cell-specific activity to a minimal TATA-containing promoter and is required for
      Nkx-2.5 activation of the ANF promoter in heterologous cells. Interestingly, in
      primary cardiocyte cultures, the NKE contributes to ANF promoter activity in a
      chamber- and developmental stage-specific manner, suggesting that Nkx-2.5 and/or
      other related cardiac proteins may play a role in chamber specification. This
      work provides the identification of a direct target for NK2 homeoproteins in the
      heart and lays the foundation for further molecular analyses of the role of Nkx
      2.5 and other NK2 proteins in cardiac development.

PMID- 8756623
TI  - Constitutive expression of murine Sak-a suppresses cell growth and induces
      multinucleation.
AB  - The murine Sak gene encodes two isoforms of a putative serine/threonine kinase,
      Sak-a and Sak-b, with a common N-terminal kinase domain and different C-terminal
      sequences. Sak is expressed primarily at sites where cell division is most active
      in adult and embryonic tissues (C. Fode, B. Motro, S. Youseli, M. Heffernan, and
      J. W. Dennis, Proc. Natl. Acad. Sci. USA 91:6388-6392, 1994). In this study, we
      found that Sak-a transcripts were absent in growth-arrested NIH 3T3 cells, while
      in cycling cells, mRNA levels increased late in G1 phase and remained elevated
      through S phase and mitosis before declining early in G1. The half-life of
      hemagglutinin epitope-tagged Sak-a protein was determined to be approximately 2
      to 3 h, and the protein was observed to be multiubiquitinated, a signal for rapid
      protein degradation. Overexpression of Sak-a protein inhibited colony-forming
      efficiency in CHO cells. Neither the Sak-b isoform nor Sak-a with a mutation in a
      strictly conserved residue in the kinase domain (Asp-154-->Asn) conferred growth
      inhibition, suggesting that both the kinase domain and the C-terminal portion of
      Sak-a are functional regions of the protein. Sak-a overexpression did not induce
      a block in the cell cycle. However, expression of HA-Sak-a, but not HA-Sak-b,
      from a constitutive promoter for 48 h in CHO cells increased the incidence of
      multinucleated cells. Our results show that Sak-a transcript levels are
      controlled in a cell cycle-dependent manner and that this precise regulation is
      necessary for cell growth and the maintenance of nuclear integrity during cell
      division.

PMID- 8756622
TI  - Interaction of the human T-cell lymphotropic virus type 1 tax transactivator with
      transcription factor IIA.
AB  - The Tax protein of human T-cell lymphotropic virus type 1 (HTLV-1) is a 40-kDa
      transcriptional activator which is critical for HTLV-1 gene regulation and virus
      induced cellular transformation. Tax is localized to the DNA through its
      interaction with the site-specific activators cyclic AMP-responsive element
      binding protein, NF-kappaB, and serum response factor. It has been suggested that
      the recruitment of Tax to the DNA positions Tax for interaction with the basal
      transcriptional machinery. On the basis of several independent assays, we now
      report a physical and functional interaction between Tax and the transcription
      factor, TFIIA. First, Tax was found to interact with the 35-kDa (alpha) subunit
      of TFIIA in the yeast two-hybrid interaction system. Importantly, two previously
      characterized mutants with point mutations in Tax, M32 (Y196A, K197S) and M41
      (H287A, P288S), which were shown to be defective in Tax-activated transcription
      were unable to interact with TFIIA in this assay. Second, a glutathione-S
      transferase (GST) affinity-binding assay showed that the interaction of holo
      TFIIA with GST-Tax was 20-fold higher than that observed with either the GST-Tax
      M32 activation mutant or the GST control. Third, a coimmunoprecipitation assay
      showed that in HTLV-1-infected human T lymphocytes, Tax and TFIIA were
      associated. Finally, TFIIA facilitates Tax transactivation in vitro and in vivo.
      In vitro transcription studies showed reduced levels of Tax-activated
      transcription in cell extracts depleted of TFIIA. In addition, transfection of
      human T lymphocytes with TFIIA expression vectors enhanced Tax-activated
      transcription of an HTLV-1 long terminal repeat-chloramphenicol acetyltransferase
      reporter construct. Our study suggests that the interaction of Tax with the
      transcription factor TFIIA may play a role in Tax-mediated transcriptional
      activation.

PMID- 8756624
TI  - Cyclin-binding motifs are essential for the function of p21CIP1.
AB  - The cyclin-dependent kinase (Cdk) inhibitor p21 is induced by the tumor
      suppressor p53 and is required for the G1-S block in cells with DNA damage. We
      report that there are two copies of a cyclin-binding motif in p21, Cy1 and Cy2,
      which interact with the cyclins independently of Cdk2. The cyclin-binding motifs
      of p21 are required for optimum inhibition of cyclin-Cdk kinases in vitro and for
      growth suppression in vivo. Peptides containing only the Cy1 or Cy2 motif
      partially inhibit cyclin-Cdk kinase activity in vitro and DNA replication in
      Xenopus egg extracts. A monoclonal antibody which recognizes the Cy1 site of p21
      specifically disrupts the association of p21 with cyclin E-Cdk2 and with cyclin
      D1-Cdk4 in cell extracts. Taken together, these observations suggest that the
      cyclin-binding motif of p21 is important for kinase inhibition and for formation
      of p21-cyclin-Cdk complexes in the cell. Finally, we show that the cyclin-Cdk
      complex is partially active if associated with only the cyclin-binding motif of
      p21, providing an explanation for how p21 is found associated with active cyclin
      Cdk complexes in vivo. The Cy sequences may be general motifs used by Cdk
      inhibitors or substrates to interact with the cyclin in a cyclin-Cdk complex.

PMID- 8756625
TI  - Complex architecture of major histocompatibility complex class II promoters:
      reiterated motifs and conserved protein-protein interactions.
AB  - The S box (also known as at the H, W, or Z box) is the 5'-most element of the
      conserved upstream sequences in promoters of major histocompatibility complex
      class II genes. It is important for their B-cell-specific and interferon gamma
      inducible expression. In this study, we demonstrate that the S box represents a
      duplication of the downstream X box. First, RFX, which is composed of the RFX5
      p36 heterodimer that binds to the X box, also binds to the S box and its 5'
      flanking sequence. Second, NF-Y, which binds to the Y box and increases
      interactions between RFX and the X box, also increases the binding of RFX to the
      S box. Third, RFXs bound to S and X boxes interact with each other in a spatially
      constrained manner. Finally, we confirmed these protein-protein and protein-DNA
      interactions by expressing a hybrid RFX5-VP16 protein in cells. We conclude that
      RFX binds to S and X boxes and that complex interactions between RFX and NF-Y
      direct B-cell-specific and interferon gamma-inducible expression or major
      histocompatibility complex class II genes.

PMID- 8756626
TI  - A new member of the hsp90 family of molecular chaperones interacts with the
      retinoblastoma protein during mitosis and after heat shock.
AB  - A gene encoding a new heat shock protein that may function as a molecular
      chaperone for the retinoblastoma protein (Rb) was characterized. The cDNA
      fragment was isolated by using the yeast two-hybrid system and Rb as bait. The
      open reading frame of the longest cDNA codes for a protein with substantial
      sequence homology to members of the hsp90 family. Antibodies prepared against
      fusions between glutathione S-transferase and portions of this new heat shock
      protein specifically recognized a 75-kDa cellular protein, hereafter designated
      hsp75, which is expressed ubiquitously and located in the cytoplasm. A unique
      LxCxE motif in hsp75, but not in other hsp90 family members, appears to be
      important for binding to the simian virus 40 T-antigen-binding domain of
      hypophosphorylated Rb, since a single mutation changing the cysteine to
      methionine abolishes the binding. In mammalian cells, Rb formed complexes with
      hsp75 under two special physiological conditions: (i) during M phase, when the
      envelope that separates the nuclear and cytoplasmic compartments broke down, and
      (ii) after heat shock, when hsp75 moved from its normal cytoplasmic location into
      the nucleus. In vitro, hsp75 had a biochemical activity to refold denatured Rb
      into its native conformation. Taken together, these results suggest that Rb may
      be a physiological substrate for the hsp75 chaperone molecule. The discovery of a
      heat shock protein that chaperones Rb identifies a mechanism, in addition to
      phosphorylation, by which Rb is regulated in response to progression of the cell
      cycle and to external stimuli.

PMID- 8756627
TI  - Yeast alpha mating factor structure-activity relationship derived from
      genetically selected peptide agonists and antagonists of Ste2p.
AB  - alpha-Factor, a 13-amino-acid pheromone secreted by haploid alpha cells of
      Saccharomyces cerevisiae, binds to Ste2p, a seven-transmembrane, G-protein
      coupled receptor present on haploid alpha cells, to activate a signal
      transduction pathway required for conjugation and mating. To determine the
      structural requirements for alpha-factor activity, we developed a genetic screen
      to identify from random and semirandom libraries novel peptides that function as
      agonists or antagonists of Ste2p. The selection scheme was based on autocrine
      strains constructed to secrete random peptides and respond by growth to those
      that were either agonists or antagonists of Ste2p. Analysis of a number of
      peptides obtained by this selection procedure indicates that Trp1, Trp3, Pro8,
      and Gly9 are important for agonist activity specifically. His2, Leu4, Leu6,
      Pro10, a hydrophobic residue 12, and an aromatic residue 13 are important for
      both agonist and antagonist activity. Our results also show that activation of
      Ste2p can be achieved with novel, unanticipated combinations of amino acids.
      Finally, the results suggest the utility of this selection scheme for identifying
      novel ligands for mammalian G-protein-coupled receptors heterologously expressed
      in S. cerevisiae.

PMID- 8756628
TI  - A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT
      activation, antiapoptotic activity, and growth regulation by IL-9.
AB  - Interleukin-9 (IL-9), a T-cell-derived cytokine, interacts with a specific
      receptor associated with the IL-2 receptor gamma chain. In this report, we
      analyze the functional domains of the human IL-9 receptor transfected into mouse
      lymphoid cell lines. Three different functions were examined: growth stimulation
      in factor-dependent pro-B Ba/F3 cells, protection against dexamethasone-induced
      apoptosis, and Ly-6A2 induction in BW5147 lymphoma cells. The results indicated
      that a single tyrosine, at position 116 in the cytoplasmic domain, was required
      for all three activities. In addition, we observed that human IL-9 reduced the
      proliferation rate of transfected BW5147 cells, an effect also dependent on the
      same tyrosine. This amino acid was necessary for IL-9-mediated tyrosine
      phosphorylation of the receptor and for STAT activation but not for IRS-2/4PS
      activation or for JAK1 phosphorylation, which depended on a domain closer to the
      plasma membrane. We also showed that JAK1 was constitutively associated with the
      IL-9 receptor. Activated STAT complexes induced by IL-9 were found to contain
      STAT1, STAT3, and STAT5 transcription factors. Moreover, sequence homologies
      between human IL-9 receptor tyrosine 116 and tyrosines (of other receptors
      activating STAT3 and STAT5 were observed. Taken together, these data indicate
      that a single tyrosine of the IL-9 receptor, required for activation of three
      different STAT proteins, is necessary for distinct activities of this cytokine,
      including proliferative responses.

PMID- 8756629
TI  - C/EBP, c-Myb, and PU.1 cooperate to regulate the neutrophil elastase promoter.
AB  - The murine neutrophil elastase (NE) gene is expressed specifically in immature
      myeloid cells. A 91-bp NE promoter region contains three cis elements which are
      conserved evolutionarily and are essential for activation of the promoter in
      differentiating 32D cl3 myeloid cells. These elements bound c-Myb (at -49),
      C/EBPalpha (at -57), and PU.1 (at -82). In NIH 3T3 cells, the NE promoter was
      activated by c-Myb, C/EBPalpha, and PU.1, via their respective binding sites.
      Cooperative activation was seen by any combination of c-Myb, C/EBPalpha, and
      PU.1, including all three together, again via their DNA-binding sites. In CV-1
      cells, but not in NIH 3T3 cells, cooperation between Myb and C/EBPalpha depended
      on the integrity of the PU.1-binding site. In addition to C/EBPalpha, C/EBPdelta
      strongly activated the NE promoter, alone or with c-Myb, but C/EBPbeta was less
      active. Either of C/EBPalpha's two transactivation domains cooperatively
      activated the promoter with c-Myb, in both NIH 3T3 and 32D c13 cells. Synergistic
      binding to DNA in a gel shift assay between C/EBPalpha, c-Myb, and PU.1 could not
      be demonstrated. Also, separation of the C/EBP- and c-Myb-binding sites by 5 or
      10 bp did not prevent cooperativity. These results suggest that a coactivator
      protein mediates cooperative activation of the NE promoter by a C/EBP and c-Myb.
      These factors, together with PU.1, direct restricted expression of the NE
      promoter to immature myeloid cells.

PMID- 8756630
TI  - Downstream 28S gene sequences on the RNA template affect the choice of primer and
      the accuracy of initiation by the R2 reverse transcriptase.
AB  - R2 non-long terminal repeat retrotransposable elements insert at a unique site in
      the 28S rRNA genes of insects. The protein encoded by the single open reading
      frame of R2 is capable of conducting the initial steps of its integration in
      vitro. The protein nicks the noncoding strand of the 28S target DNA (the strand
      which serves as a template for RNA synthesis) and uses the 3' hydroxyl group
      exposed by this nick to prime reverse transcription of the R2 RNA template. This
      target-primed reverse transcription (TPRT) reaction requires that the RNA
      template contains the 250-nucleotide 3' untranslated region of the R2 element. If
      this RNA template ends at the precise 3' end of the R2 element, then extra
      nucleotides, which we refer to as nontemplated nucleotides, are added to the
      target before cDNA synthesis. The presence of downstream 28S gene sequences on
      the RNA template reduces the total efficiency but eliminates these nontemplated
      additions, resulting in nearly 90% of all TPRT products reproducing the 3'
      junctions seen in vivo. Templates with 5 to 10 nucleotides of the 28S sequence
      are used most efficiently in this in vitro TPRT reaction. The requirement for
      downstream 28S rRNA sequences probably explains why the R2 elements of most
      insects differ from the majority of non-long terminal repeat retrotransposons in
      that they do not contain an A-rich repeat at their 3' junction with the target
      DNA. The presence of downstream sequences on these in vitro R2 templates also
      revealed that the R2 reverse transcriptase can prime cDNA synthesis by using the
      3' end of another RNA molecule. This RNA-primed cDNA synthesis is not based on
      sequence complementarity between the RNA primer and the R2 template. The ability
      to use the 3' end of a noncomplementary RNA molecule has also been seen with the
      reverse transcriptase of the mitochondrial Mauriceville plasmid of Neurospora
      crassa.

PMID- 8756631
TI  - In vivo and in vitro specificity of protein tyrosine kinases for immunoglobulin G
      receptor (FcgammaRII) phosphorylation.
AB  - Human B cells express four immunoglobulin G receptors, FcgammaRIIa, FcgammaRIIb1,
      FcgammaRIIb2, and FcgammaRIIc. Coligation of either FcgammaRII isoform with the B
      cell antigen receptor (BCR) results in the abrogation of B-cell activation, but
      only the FcgammaRIIa/c and FcgammaIIb1 isoforms become phosphorylated. To
      identify the FcgammaRII-phosphorylating protein tyrosine kinase (PTK), we used
      the combination of an in vitro and an in vivo approach. In an in vitro assay
      using recombinant cytoplasmic tails of the different FcgammaRII isoforms as well
      as tyrosine exchange mutants, we show that each of the BCR-associated PTKs (Lyn,
      Blk, Fyn, and Syk) shows different phosphorylation patterns with regard to the
      different FcgammaR isoforms and point mutants. While each PTK phosphorylated
      FcgammaRIIa/c, FcgammaRIIb1 was phosphorylated by Lyn and Blk whereas
      FcgammaRIIb2 became phosphorylated only by Blk. Mutants lacking both tyrosine
      residues of the immune receptor tyrosine-based activation motif (ITAM) of
      FcgammaRIIa/c were not phosphorylated by Blk and Fyn, while Lyn-mediated
      phosphorylation was dependent on the presence of the C-terminal tyrosine of the
      ITAM. Results obtained in assays using an FcgammaR- B-cell line transfected with
      wild-type or mutated FcgammaRIIa demonstrated that exchange of the C-terminal
      tyrosine of the ITAM of FcgammaRIIa/c was sufficient to abolish FcgammaRIIa/c
      phosphorylation in B cells. Additionally, we could show that Lyn and Fyn bind to
      FcgammaRIIa/c, with the ITAM being necessary for association. Comparison of the
      phosphorylation pattern of each PTK observed in vitro with the phosphorylation
      pattern observed in vivo suggests that Lyn is the most likely candidate for
      FcgammaRIIa/c and FcgammaRIIb1 phosphorylation in vivo.

PMID- 8756632
TI  - The nuclear factor YY1 suppresses the human gamma interferon promoter through two
      mechanisms: inhibition of AP1 binding and activation of a silencer element.
AB  - Our group has previously reported that the nuclear factor Yin-Yang 1 (YY1), a
      ubiquitous DNA-binding protein, is able to interact with a silencer element (BE)
      in the gamma interferon (IFN-gamma) promoter region. In this study, we
      demonstrated that YY1 can directly inhibit the activity of the IFN-gamma promoter
      by interacting with multiple sites in the promoter. In cotransfection assays, a
      YY1 expression vector significantly inhibited IFN-gamma promoter activity.
      Mutation of the YY1 binding site in the native IFN-gamma promoter was associated
      with an increase in the IFN-gamma promoter activity. Analysis of the DNA
      sequences of the IFN-gamma promoter revealed a second functional YY1 binding site
      (BED) that overlaps with an AP1 binding site. In this element, AP1 enhancer
      activity was suppressed by YY1. Since the nuclear level of YY1 does not change
      upon cell activation, our data support a model that the nuclear factor YY1 acts
      to suppress basal IFN-gamma transcription by interacting with the promoter at
      multiple DNA binding sites. This repression can occur through two mechanisms: (i)
      cooperation with an as-yet-unidentified AP2-like repressor protein and (ii)
      competition for DNA binding with the transactivating factor AP1.

PMID- 8756633
TI  - An essential E box in the promoter of the gene encoding the mRNA cap-binding
      protein (eukaryotic initiation factor 4E) is a target for activation by c-myc.
AB  - The mRNA cap-binding protein (eukaryotic initiation factor 4E [eIF4E]) binds the
      m7 GpppN cap on mRNA, thereby initiating translation. eIF4E is essential and rate
      limiting for protein synthesis. Overexpression of eIF4E transforms cells, and
      mutations in eIF4E arrest cells in G, in cdc33 mutants. In this work, we
      identified the promoter region of the gene encoding eIF4E, because we previously
      identified eIF4E as a potential myc-regulated gene. In support of our previous
      data, a minimal, functional, 403-nucleotide promoter region of eIF4E was found to
      contain CACGTG E box repeats, and this core eIF4E promoter was myc responsive in
      cotransfections with c-myc. A direct role for myc in activating the eIF4E
      promoter was demonstrated by cotransfections with two dominant negative mutants
      of c-myc (MycdeltaTAD and MycdeltaBR) which equally suppressed promoter function.
      Furthermore, electrophoretic mobility shift assays demonstrated quantitative
      binding to the E box motifs that correlated with myc levels in the
      electrophoretic mobility shift assay extracts; supershift assays demonstrated max
      and USF binding to the same motif. cis mutations in the core or flank of the
      eIF4E E box simultaneously altered myc-max and USF binding and inactivated the
      promoter. Indeed, mutations of this E box inactivated the promoter in all cells
      tested, suggesting it is essential for expression of eIF4E. Furthermore, the
      GGCCACGTG(A/T)C(C/G) sequence is shared with other in vivo targets for c-myc, but
      unlike other targets, it is located in the immediate promoter region. Its
      critical function in the eIF4E promoter coupled with the known functional
      significance of eIF4E in growth regulation makes it a particularly interesting
      target for c-myc regulation.

PMID- 8756634
TI  - Csk enhances insulin-stimulated dephosphorylation of focal adhesion proteins.
AB  - Insulin has pleiotropic effects on the regulation of cell physiology through
      binding to its receptor. The wide variety of tyrosine phosphorylation motifs of
      insulin receptor substrate 1 (IRS-1), a substrate for the activated insulin
      receptor tyrosine kinase, may account for the multiple functions of insulin.
      Recent studies have shown that activation of the insulin receptor leads to the
      regulation of focal adhesion proteins, such as a dephosphorylation of focal
      adhesion kinase (pp125FAK). We show here that C-terminal Src kinase (Csk), which
      phosphorylates C-terminal tyrosine residues of Src family protein tyrosine
      kinases and suppresses their kinase activities, is involved in this insulin
      stimulated dephosphorylation of focal adhesion proteins. We demonstrated that the
      overexpression of Csk enhanced and prolonged the insulin-induced
      dephosphorylation of pp125FAK. Another focal adhesion protein, paxillin, was also
      dephosphorylated upon insulin stimulation, and a kinase-negative mutant of Csk
      was able to inhibit the insulin-induced dephosphorylation of pp125FAK and
      paxillin. Although we have shown that the Csk Src homology 2 domain can bind to
      several tyrosine-phosphorylated proteins, including pp125FAK and paxillin, a
      majority of protein which bound to Csk was IRS-1 when cells were stimulated by
      insulin. Our data also indicated that tyrosine phosphorylation levels of IRS-1
      appear to be paralleled by the dephosphorylation of the focal adhesion proteins.
      We therefore propose that the kinase activity of Csk, through the insulin-induced
      complex formation of Csk with IRS-1, is involved in insulin's regulation of the
      phosphorylation levels of the focal adhesion proteins, possibly through
      inactivation of the kinase activity of c-Src family kinases.

PMID- 8756635
TI  - Involvement of the molecular chaperone Ydj1 in the ubiquitin-dependent
      degradation of short-lived and abnormal proteins in Saccharomyces cerevisiae.
AB  - In Escherichia coli and mitochondria, the molecular chaperone DnaJ is required
      not only for protein folding but also for selective degradation of certain
      abnormal polypeptides. Here we demonstrate that in the yeast cytosol, the
      homologous chaperone Ydj1 is also required for ubiquitin-dependent degradation of
      certain abnormal proteins. The temperature-sensitive ydj1-151 mutant showed a
      large defect in the overall breakdown of short-lived cell proteins and abnormal
      polypeptides containing amino acid analogs, especially at 38 degrees C. By
      contrast, the degradation of long-lived cell proteins, which is independent of
      ubiquitin, was not altered nor was cell growth affected. The inactivation of Ydj1
      markedly reduced the rapid, ubiquitin-dependent breakdown of certain beta
      galactosidase (beta-gal) fusion polypeptides. Although degradation of N-end rule
      substrates (arginine-beta-gal and leucine-beta-gal) and the B-type cyclin Clb5
      beta-gal occurred normally, degradation of the abnormal polypeptide ubiquitin
      proline-beta-gal (Ub-P-beta-gal) and that of the short-lived normal protein Gcn4
      were inhibited. As a consequence of reduced degradation of Ub-P-beta-gal, the
      beta-gal activity was four to five times higher in temperature-sensitive ydj1-151
      mutant cells than in wild-type cells; thus, the folding and assembly of this
      enzyme do not require Ydj1 function. In wild-type cells, but not in ydj1-151
      mutant cells, this chaperone is associated with the short-lived substrate Ub-P
      beta-gal and not with stable beta-gal constructs. Furthermore, in the ydj1-151
      mutant, the ubiquitination of Ub-P-beta-gal was blocked and the total level of
      ubiquitinated protein in the cell was reduced. Thus, Ydj1 is essential for the
      ubiquitin-dependent degradation of certain proteins. This chaperone may
      facilitate the recognition of unfolded proteins or serve as a cofactor for
      certain ubiquitin-ligating enzymes.

PMID- 8756636
TI  - Semidominant mutations in the yeast Rad51 protein and their relationships with
      the Srs2 helicase.
AB  - Suppressors of the methyl methanesulfonate sensitivity of Saccharomyces
      cerevisiae diploids lacking the Srs2 helicase turned out to contain semidominant
      mutations in Rad5l, a homolog of the bacterial RecA protein. The nature of these
      mutations was determined by direct sequencing. The 26 mutations characterized
      were single base substitutions leading to amino acid replacements at 18 different
      sites. The great majority of these sites (75%) are conserved in the family of
      RecA-like proteins, and 10 of them affect sites corresponding to amino acids in
      RecA that are probably directly involved in ATP reactions, binding, and/or
      hydrolysis. Six mutations are in domains thought to be involved in interaction
      between monomers; they may also affect ATP reactions. By themselves, all the
      alleles confer a rad5l null phenotype. When heterozygous, however, they are, to
      varying degrees, negative semidominant for radiation sensitivity; presumably the
      mutant proteins are coassembled with wild-type Rad51 and poison the resulting
      nucleofilaments or recombination complexes. This negative effect is partially
      suppressed by an SRS2 deletion, which supports the hypothesis that Srs2 reverses
      recombination structures that contain either mutated proteins or numerous DNA
      lesions.

PMID- 8756637
TI  - Two zinc-finger-containing repressors are responsible for glucose repression of
      SUC2 expression.
AB  - Expression of the SUC2 gene in Saccharomyces cerevisiae, which encodes invertase,
      is repressed about 200-fold by high levels of glucose. Mig1p is a Cys2His2 zinc
      finger-containing protein required for glucose repression of SUC2 and several
      other genes. However, SUC2 expression is still about 13-fold repressed by glucose
      in a mig1 mutant. We have identified a second repressor, Mig2p, containing zinc
      fingers very similar to those of Mig1p that is responsible for this remaining
      glucose repression of SUC2 expression. Overexpression of MIG2 represses SUC2
      under nonrepressing conditions, and a LexA-Mig2p fusion represses transcription
      of a lexO-containing promoter in a glucose-dependent manner, supporting the idea
      that Mig2p is a glucose-activated repressor. We have shown that Mig2p binds to
      the Miglp-binding sites in the SUC2 promoter. Even though Mig1p and Mig2p bind to
      similar sites and share almost identical zinc fingers, they differ in their
      relative affinities for various Mig1p-binding sites. This could explain our
      observation that MIG2 appears to have little role in glucose repression of other
      promoters with MIG1-binding sites.

PMID- 8756638
TI  - Single-stranded-DNA binding alters human replication protein A structure and
      facilitates interaction with DNA-dependent protein kinase.
AB  - Human replication protein A (hRPA) is an essential single-stranded-DNA-binding
      protein that stimulates the activities of multiple DNA replication and repair
      proteins through physical interaction. To understand DNA binding and its role in
      hRPA heterologous interaction, we examined the physical structure of hRPA
      complexes with single-stranded DNA (ssDNA) by scanning transmission electron
      microscopy. Recent biochemical studies have shown that hRPA combines with ssDNA
      in at least two binding modes: by interacting with 8 to 10 nucleotides (hRPA8nt)
      and with 30 nucleotides (hRPA30nt). We find the relatively unstable hRPA8nt
      complex to be notably compact with many contacts between hRPA molecules. In
      contrast, on similar lengths of ssDNA, hRPA30nt complexes align along the DNA and
      make few intermolecular contacts. Surprisingly, the elongated hRPA30nt complex
      exists in either a contracted or an extended form that depends on ssDNA length.
      Therefore, homologous-protein interaction and available ssDNA length both
      contribute to the physical changes that occur in hRPA when it binds ssDNA. We
      used activated DNA-dependent protein kinase as a biochemical probe to detect
      alterations in conformation and demonstrated that formation of the extended
      hRPA30nt complex correlates with increased phosphorylation of the hRPA 29-kDa
      subunit. Our results indicate that hRPA binds ssDNA in a multistep pathway,
      inducing new hRPA alignments and conformations that can modulate the functional
      interaction of other factors with hRPA.

PMID- 8756639
TI  - The murine DUB-1 gene is specifically induced by the betac subunit of interleukin
      3 receptor.
AB  - Cytokines regulate cell growth and differentiation by inducing the expression of
      specific target genes. We have recently isolated a cytokine-inducible, immediate
      early cDNA, DUB-1, that encodes a deubiquitinating enzyme. The DUB-1 mRNA was
      specifically induced by the receptors for interleukin-3, granulocyte-macrophage
      colony-stimulating factor, and interleukin-5, suggesting a role for the beta
      common (betac subunit known to be shared by these receptors. In order to identify
      the mechanism of cytokine induction, we isolated a murine genomic clone for DUB-1
      containing a functional promoter region. The DUB-1 gene contains two exons, and
      the nucleotide sequence of its coding region is identical to the sequence of DUB
      1 cDNA. Various regions of the 5' flanking region of the DUB-1 gene were assayed
      for cytokine-inducible activity. An enhancer region that retains the beta c
      specific inducible activity of the DUB-1 gene was identified. Enhancer activity
      was localized to a 112-bp fragment located 1.4 kb upstream from the ATG start
      codon. Gel mobility shift assays revealed two specific protein complexes that
      bound to this minimal enhancer region. One complex was induced by betac
      signaling, while the other was noninducible. Finally, the membrane-proximal
      region of human betac was required for DUB-1 induction. In conclusion, DUB-1 is
      the first example of an immediate-early gene that is induced by a specific
      subunit of a cytokine receptor. Further analysis of the DUB-1 enhancer element
      may reveal specific determinants of a betac-specific signaling pathway.

PMID- 8756640
TI  - Agonist-specific conformational changes in the yeast alpha-factor pheromone
      receptor.
AB  - The yeast alpha-factor pheromone receptor is a member of the G-protein-coupled
      receptor family. Limited trypsin digestion of yeast membranes was used to
      investigate ligand-induced conformational changes in this receptor. The agonist,
      alpha-factor, accelerated cleavage in the third intracellular loop, whereas the
      antagonist, desTrp1,Ala3-alpha-factor, reduced the cleavage rate. Thus, the
      enhanced accessibility of the third intracellular loop is specific to the
      agonist. alpha-Factor inhibited cleavage weakly at a second site near the
      cytoplasmic terminus of the seventh transmembrane helix, whereas the antagonist
      showed a stronger inhibition of cleavage at this site and at another site in the
      C-terminal domain of the receptor. The alpha-factor-induced conformational
      changes appeared to be inherent properties of the receptor, as they were retained
      in G-protein-deficient mutants. Moreover, a mutant receptor (ste2-L236H) that
      affects the third loop and is defective for G-protein coupling retained the
      ability to undergo the agonist-induced conformational changes. These results are
      consistent with a model in which G-protein activation is limited by the
      availability of specific contacts between the G protein and the third
      intracellular loop of the receptor. The antagonist appears to promote a distinct
      conformational state that differs from either the unoccupied or the agonist
      occupied state.

PMID- 8756641
TI  - Ca2+-calmodulin promotes survival of pheromone-induced growth arrest by
      activation of calcineurin and Ca2+-calmodulin-dependent protein kinase.
AB  - The cmd1-6 allele contains three mutations that block Ca2+ binding to calmodulin
      from Saccharomyces cerevisiae. We find that strains containing cmd1-6 lose
      viability during cell cycle arrest induced by the mating pheromone alpha-factor.
      The 50% lethal dose (LD50) of alpha-factor for the calmodulin mutant is almost
      fivefold below the LD50 for a wild-type strain. The calmodulin mutants are not
      more sensitive to alpha-factor, as measured by activation of a pheromone
      responsive reporter gene. Two observations indicate that activation of the Ca2+
      calmodulin-dependent protein phosphatase calcineurin contributes to survival of
      pheromone-induced arrest. First, deletion of the gene encoding the calcineurin
      regulatory B subunit, CNB1, from a wild-type strain decreases the LD50 of alpha
      factor but has no further effect on a cmd1-6 strain. Second, a dominant
      constitutive calcineurin mutant partially restores the ability of the cmd1-6
      strain to survive exposure to alpha-factor. Activation of the Ca2+-calmodulin
      dependent protein kinase (CaMK) also contributes to survival, thus revealing a
      new function for this enzyme. Deletion of the CMK1 and CMK2 genes, which encode
      CaMK, decreases the LD50 of pheromone compared with that for a wild-type strain
      but again has no effect in a cmd1-6 strain. Furthermore, the LD50 of alpha-factor
      for a mutant in which the calcineurin and CaMK genes have been deleted is the
      same as that for the calmodulin mutant. Finally, the CaMK and calcineurin
      pathways appear to be independent since the ability of constitutive calcineurin
      to rescue a cmd1-6 strain is not blocked by deletion of the CaMK genes.

PMID- 8756642
TI  - Human Rad50 is physically associated with human Mre11: identification of a
      conserved multiprotein complex implicated in recombinational DNA repair.
AB  - In this report, we describe the identification and molecular characterization of
      a human RAD50 homolog, hRAD50. hRAD50 was included in a collection of cDNAs which
      were isolated by a direct cDNA selection strategy focused on the chromosomal
      interval spanning 5q23 to 5q31. Alterations of the 5q23-q31 interval are
      frequently observed in myelodysplasia and myeloid leukemia. This strategy was
      thus undertaken to create a detailed genetic map of that region. Saccharomyces
      cerevisiae RAD50 (ScRAD50) is one of three yeast RAD52 epistasis group members
      (ScRAD50, ScMRE11, and ScXRS2) in which mutations eliminate meiotic recombination
      but confer a hyperrecombinational phenotype in mitotic cells. The yeast Rad50,
      Mre11, and Xrs2 proteins appear to act in a multiprotein complex, consistent with
      the observation that the corresponding mutants confer essentially identical
      phenotypes. In this report, we demonstrate that the human Rad50 and Mre11
      proteins are stably associated in a protein complex which may include three other
      proteins. hRAD50 is expressed in all tissues examined, but mRNA levels are
      significantly higher in the testis. Other human RAD52 epistasis group homologs
      exhibit this expression pattern, suggesting the involvement of human RAD52
      epistasis group proteins in meiotic recombination. Human RAD52 epistasis group
      proteins are highly conserved and act in protein complexes that are analogous to
      those of their yeast counterparts. These findings indicate that the function of
      the RAD52 epistasis group is conserved in human cells.

PMID- 8756643
TI  - HOXB7 constitutively activates basic fibroblast growth factor in melanomas.
AB  - Homeobox (HOX) genes control axial specification during mammalian development and
      also regulate skin morphogenesis. Although selected HOX genes are variably
      expressed in leukemias and kidney and colon cancer cell lines, their relationship
      with the neoplastic phenotype remains unclear. In both normal development and
      neoplastic transformation, HOX target genes are largely unknown. We investigated
      the expression and function of HOXB cluster genes in human melanoma. The HOXB7
      gene was constitutively expressed in all 25 melanoma cell lines and analyzed
      under both normal and serum-starved conditions, as well as in in vivo primary and
      metastatic melanoma cells; conversely, HOXB7 was expressed in proliferating but
      not quiescent normal melanocytes. Treatment of melanoma cell lines with antisense
      oligomers targeting HOXB7 mRNA markedly inhibited cell proliferation and
      specifically abolished expression of basic fibroblast growth factor (bFGF) mRNA.
      Band shift and cotransfection experiments showed that HOXB7 directly
      transactivates the hFGF gene through one out of five putative homeodomain binding
      sites present in its promoter. These novel findings indicate a key role for
      constitutive HOXB7 expression in melanoma cell proliferation via bFGF. The
      results also raise the possibility that growth factor genes are critical HOX
      target genes in other developmental and/or neoplastic cell systems.

PMID- 8756644
TI  - HHR23B, a human Rad23 homolog, stimulates XPC protein in nucleotide excision
      repair in vitro.
AB  - A protein complex which specifically complements defects of XP-C cell extracts in
      vitro was previously purified to near homogeneity from HeLa cells. The complex
      consists of two tightly associated proteins: the XPC gene product and HHR23B, one
      of two human homologs of the Saccharomyces cerevisiae repair gene product Rad23
      (Masutani et al., EMBO J. 13:1831-1843, 1994). To elucidate the roles of these
      proteins in "genome-overall" repair, we expressed the XPC protein in a
      baculovirus system and purified it to near homogeneity. The recombinant human XPC
      (rhXPC) protein exhibited a high level of affinity for single-stranded DNA and
      corrected the repair defect in XP-C whole-cell extracts without extra addition of
      recombinant HHR23B (rHHR23B) protein. However, Western blot (immunoblot)
      experiments revealed that XP-C cell extracts contained excess endogenous HHR23B
      protein, which might be able to form a complex upon addition of the rhXPC
      protein. To investigate the role of HHR23B, we fractionated the XP-C cell
      extracts and constructed a reconstituted system in which neither endogenous XPC
      nor HHR23B proteins were present. In this assay system, rhXPC alone weakly
      corrected the repair defect, while significant enhancement of the correcting
      activity was observed upon coaddition of rHHR23B protein. Stimulation of XPC by
      HHR23B was found with simian virus 40 minichromosomes as well as with naked
      plasmid DNA and with UV- as well as N-acetoxy-2- acetylfluorene-induced DNA
      lesions, indicating a general role of HHR23B in XPC functioning in the genome
      overall nucleotide excision repair subpathway.

PMID- 8756645
TI  - Domains A and B in the Rb pocket interact to form a transcriptional repressor
      motif.
AB  - The retinoblastoma protein (Rb) is a tumor suppressor that regulates progression
      from the G1 phase to the S phase of the cell cycle. Previously, we found that Rb
      is a transcriptional repressor that is selectively targeted to promoters through
      an interaction with the E2F family of cell cycle transcription factors--when Rb
      is tethered to a promoter through E2F, it not only blocks E2F activity, it also
      binds surrounding transcription factors, preventing their interaction with the
      basal transcription complex, thus resulting in a dominant inhibitory effect on
      transcription of cell cycle genes. Here we examine the repressor motif of Rb. The
      two domains in the Rb pocket, A and B, which are conserved across species and in
      the Rb-related proteins p107 and p130, are both required for repressor activity.
      The nonconserved spacer separating A and B is not required. Although neither A
      nor B alone had any repressor activity, surprisingly, repressor activity was
      observed when the domains were coexpressed on separate proteins. Transfection
      assays suggest that one domain can recruit the other to the promoter to form a
      repressor motif that can both interact with E2F and have a dominant inhibitory
      effect on transcription. Using coimmunoprecipitation and in vitro binding assays,
      we show that A and B interact directly and that mutations which disrupt this
      interaction inhibit repressor activity. The Rb pocket was originally defined as
      the binding site for oncoproteins from DNA tumor viruses such as adenovirus E1a.
      We present evidence that E1a interacts with a site formed by the interaction of A
      and B and that this interaction with A and B induces or stabilizes the A-B
      interaction.

PMID- 8756647
TI  - Phosphorylation of Ga14p at a single C-terminal residue is necessary for
      galactose-inducible transcription.
AB  - Gal4p regulates expression of genes necessary for galactose catabolism in
      Saccharomyces cerevisiae. We have previously shown that phosphorylation of Gal4p
      requires both its DNA binding and transcriptional-activation functions and have
      suggested that phosphorylation occurs as a consequence of interaction with
      general transcription factors. In this study, we show that phosphorylation occurs
      rapidly on a limited fraction of overexpressed Gal4p present in a sodium dodecyl
      sulfate-extractable subcellular fraction while a significant fraction remains
      stably unphosphorylated. Taken together with our previous observations, we
      conclude that Gal4p is phosphorylated only if it becomes localized to the nucleus
      and is capable of both DNA binding and transcriptional activation. We demonstrate
      that Gal4p is multiply phosphorylated at both the C and N termini, and we
      identify the precise locations of three sites of phosphorylation at serines 691,
      696, and 699. Of these sites, only serine 699 must be phosphorylated for
      galactose-inducible transcription to occur. Mutation of S-699 to alanine
      significantly impairs GAL induction by galactose in GAL80+ cells but does not
      affect transcriptional activation by Gal4p in gal80- cells. In gal80- cells,
      Gal4p phosphorylation, including that of serine 699, is stimulated by the
      presence of both galactose and glucose, indicating that phosphorylation at this
      site is not specifically activated by galactose. Serine 699 phosphorylation
      requires Gal4p's DNA binding function and is influenced by the function of the
      RNA polymerase II holoenzyme component Gal11p. These results suggest that a
      phosphorylation on Gal4p, likely resulting from interaction with the holoenzyme,
      modulates the induction process by regulating interaction between Gal4p and
      Gal80p.

PMID- 8756648
TI  - The N-terminal pleckstrin, coiled-coil, and IQ domains of the exchange factor Ras
      GRF act cooperatively to facilitate activation by calcium.
AB  - We have recently shown that the neuronal exchange factor p140 Ras-GRF becomes
      activated in vivo in response to elevated calcium levels [C. L. Farnsworth, N. W.
      Freshney, L. B. Rosen, A. Ghosh, M. E. Greenberg, and L. A. Feig, Nature (London)
      376:524-527, 1995]. Activation is mediated by calcium-induced calmodulin binding
      to an IQ domain near the N terminus of Ras-GRF. Here we show that the adjacent N
      terminal pleckstrin homology (PH), coiled-coil, and IQ domains function
      cooperatively to allow Ras-GRF activation. Deletion of the N-terminal PH domain
      redistributes a large percentage of Ras-GRF from the particulate to the cytosolic
      fraction of cells and renders the protein insensitive to calcium stimulation. A
      similar cellular distribution and biological activity are observed when only the
      core catalytic domain is expressed. Although the PH domain is necessary for
      particulate association of Ras-GRF, it is not sufficient for targeting the core
      catalytic domain to this cellular location. This requires the PH domain and the
      adjacent coiled-coil and IQ sequences. Remarkably, this form of Ras-GRF is
      constitutively activated. The PH and coiled-coil domains must also perform an
      additional function, since targeting to the particulate fraction of cells is not
      sufficient to allow Ras-GRF activation by calcium. A Ras-GRF mutant containing
      the PH domain from Ras-GTPase-activating protein in place of its own N-terminal
      PH domain localizes to the particulate fraction of cells but does not respond to
      calcium. Similar phenotypes are seen with mutant Ras-GRFs containing point
      mutations in either the PH or coiled-coil domain. These findings argue that the N
      terminal PH, coiled-coil, and IQ domains of Ras-GRF function together to connect
      Ras-GRF to multiple components in the particulate fractions of cells that are
      required for responsiveness of the protein to calcium signaling.

PMID- 8756646
TI  - The Ras GTPase-activating-protein-related human protein IQGAP2 harbors a
      potential actin binding domain and interacts with calmodulin and Rho family
      GTPases.
AB  - We previously described IQGAP1 as a human protein related to a putative Ras
      GTPase-activating protein (RasGAP) from the fission yeast Schizosaccharomyces
      pombe. Here we report the identification of a liver-specific human protein that
      is 62% identical to IQGAP1. Like IQGAP1, the novel IQGAP2 protein harbors an N
      terminal calponin homology motif which functions as an F-actin binding domain in
      members of the spectrin, filamin, and fimbrin families. Both IQGAPs also harbor
      several copies of a novel 50- to 55-amino-acid repeat, a single WW domain, and
      four IQ motifs and have 25% sequence identity with almost the entire S. pombe
      sar1 RasGAP homolog. As predicted by the presence of IQ motifs, IQGAP2 binds
      calmodulin. However, neither full-length nor truncated IQGAP2 stimulated the
      GTPase activity of Ras or its close relatives. Instead, IQGAP2 binds Cdc42 and
      Racl but not RhoA. This interaction involves the C-terminal half of IQGAP2 and
      appears to be independent of the nucleotide binding status of the GTPases.
      Although IQGAP2 shows no GAP activity towards Cdc42 and Rac1, the protein did
      inhibit both the intrinsic and RhoGAP-stimulated GTP hydrolysis rates of Cdc42
      and Rac1, suggesting an alternative mechanism via which IQGAPs might modulate
      signaling by these GTPases. Since IQGAPs harbor a potential actin binding domain,
      they could play roles in the Cdc42 and Rac1 controlled generation of specific
      actin structures.

PMID- 8756649
TI  - The EH-domain-containing protein Pan1 is required for normal organization of the
      actin cytoskeleton in Saccharomyces cerevisiae.
AB  - Normal cell growth and division in the yeast Saccharomyces cerevisiae involve
      dramatic and frequent changes in the organization of the actin cytoskeleton.
      Previous studies have suggested that the reorganization of the actin cytoskeleton
      in accordance with cell cycle progression is controlled, directly or indirectly,
      by the cyclin-dependent kinase Cdc28. Here we report that by isolating rapid
      death mutants in the background of the Start-deficient cdc28-4 mutation, the
      essential yeast gene PAN1, previously thought to encode the yeast poly(A)
      nuclease, is identified as a new factor required for normal organization of the
      actin cytoskeleton. We show that at restrictive temperature, the pan1 mutant
      exhibited abnormal bud growth, failed to maintain a proper distribution of the
      actin cytoskeleton, was unable to reorganize actin the cytoskeleton during cell
      cycle, and was defective in cytokinesis. The mutant also displayed a random
      pattern of budding even at permissive temperature. Ectopic expression of PAN1 by
      the GAL promoter caused abnormal distribution of the actin cytoskeleton when a
      single-copy vector was used. Immunofluorescence staining revealed that the Pan1
      protein colocalized with the cortical actin patches, suggesting that it may be a
      filamentous actin-binding protein. The Pan1 protein contains an EF-hand calcium
      binding domain, a putative Src homology 3 (SH3)-binding domain, a region similar
      to the actin cytoskeleton assembly control protein Sla1, and two repeats of a
      newly identified protein motif known as the EH domain. These findings suggest
      that Pan1, recently recognized as not responsible for the poly(A) nuclease
      activity (A. B. Sachs and J. A. Deardorff, erratum, Cell 83:1059, 1995; R. Boeck,
      S. Tarun, Jr., M. Rieger, J. A. Deardorff, S. Muller-Auer, and A. B. Sachs, J.
      Biol. Chem. 271:432-438, 1996), plays an important role in the organization of
      the actin cytoskeleton in S. cerevisiae.

PMID- 8756650
TI  - Composite patterns in neutral/neutral two-dimensional gels demonstrate
      inefficient replication origin usage.
AB  - The neutral/neutral two-dimensional (2-D) gel replicon mapping technique has been
      used to great advantage to localize and characterize origins of replication.
      Interestingly, many yeast origins display a composite pattern consisting of both
      a bubble arc and a single-fork arc. Moreover, in every instance in which
      neutral/neutral 2-D gels have been used to analyze origins in higher eukaryotic
      cells, two or more adjacent fragments display these composite patterns. We
      believe that composite patterns signal inefficient origin usage in yeast cells
      because the replicators in question are not active in every cell cycle and in
      higher eukaryotic replicons because initiation sites are chosen from among many
      potential sites lying within a zone. However, others have suggested that the
      single-fork arcs in these composite gel patterns arise from nicking activity that
      converts replication bubbles to branched structures that comigrate with bona fide
      single forks. Here, we have used three different replicon mapping strategies to
      show that broken simian virus 40 replication bubbles trace unique arcs that are
      clearly distinguishable from classic, intact single forks. Thus, it is likely
      that composite 2-D gel patterns represent origins that are inefficiently
      utilized.

PMID- 8756651
TI  - Characterizing replication intermediates in the amplified CHO dihydrofolate
      reductase domain by two novel gel electrophoretic techniques.
AB  - Using neutral/neutral and neutral/alkaline two-dimensional (2-D) gel techniques,
      we previously obtained evidence that initiation can occur at any of a large
      number of sites distributed throughout a broad initiation zone in the
      dihydrofolate reductase (DHFR) domain of Chinese hamster ovary (CHO) cells.
      However, other techniques have suggested a much more circumscribed mode of
      initiation in this locus. This dichotomy has raised the issue whether the
      patterns of replicating DNA on 2-D gels have been misinterpreted and, in some
      cases, may represent such noncanonical replication intermediates as broken
      bubbles or microbubbles. In an accompanying study (R. F. Kalejta and J. L.
      Hamlin, Mol. Cell. Biol. 16:4915-4922, 1996), we have shown that broken bubbles
      migrate to unique positions in three different gel systems and therefore are not
      likely to be confused with classic replication intermediates. Here, we have
      applied a broken bubble assay developed from that study to an analysis of the
      amplified DHFR locus in CHO cells. This assay gives information about the number
      and positions of initiation sites within a fragment. In addition, we have
      analyzed the DHFR locus by a novel stop-and-go-alkaline gel technique that
      measures the size of nascent strands at all positions along each arc in a
      neutral/neutral 2-D gel. Results of these analyses support the view that the 2-D
      gel patterns previously assigned to classic, intact replication bubbles and
      single-forked structures indeed correspond to these entities. Furthermore,
      potential nascent-strand start sites appear to be distributed at very frequent
      intervals along the template in the intergenic region in the DHFR domain.

PMID- 8756652
TI  - Enhancement of antiproliferative activity of gamma interferon by the specific
      inhibition of tyrosine dephosphorylation of Stat1.
AB  - Gamma interferon (IFN-gamma) signals to the nucleus through the activation, by
      tyrosine phosphorylation, of the latent cytoplasmic transcription factor Stat1
      (signal transducer and activator of transcription). It has been demonstrated that
      the activity of Stat1 is dependent on tyrosine phosphorylation which is regulated
      by Jak tyrosine kinases as well as by the as-yet-unidentified protein tyrosine
      phosphatase. We report that the N-terminal domain of Stat1, which is highly
      conserved among all STAT family members, is required for its tyrosine
      dephosphorylation. A single amino acid substitution (Arg-31 to Ala) in the Stat1
      N-terminal domain inhibited Stat1 tyrosine dephosphorylation. The deletion of the
      Stat1 N-terminal domain resulted in a mutant Stat1 protein which was
      constitutively phosphorylated on Tyr-701. Upon IFN-gamma stimulation, the
      tyrosine phosphorylation of this mutant protein was further enhanced but was not
      down-regulated by protein tyrosine phosphatase in vivo. When expressed in NIH 3T3
      cells, this mutant protein greatly enhanced the antiproliferative activity of IFN
      gamma. We suggest that the N-terminal domains of STATs are crucial for modulating
      STAT activities through regulating the tyrosine dephosphorylation of STATs.

PMID- 8756653
TI  - RNA structure is a critical determinant of poly(A) site recognition by cleavage
      and polyadenylation specificity factor.
AB  - Sequence conservation among mammalian poly(A) sites is limited to the sequence
      AAUAAA, coupled with an amorphous downstream U- or GU-rich region. Since these
      sequences may also occur within the coding region of mRNAs, additional
      information must be required to define authentic poly(A) sites. Several poly(A)
      sites have been shown to contain sequences outside the core elements that enhance
      the efficiency of 3' processing in vivo and in vitro. The human immunodeficiency
      virus type 1, equine infectious anemia virus, and adenovirus L1 3' processing
      enhancers have been shown to promote the binding of cleavage and polyadenylation
      specificity factor (CPSF), the factor responsible for recognition of AAUAAA, to
      the pre-mRNA, thereby facilitating the assembly of a stable 3' processing
      complex. We have used in vitro selection to examine the mechanism by which the
      human immunodeficiency virus type 1 3' processing enhancer promotes the
      interaction of CPSF with the AAUAAA hexamer. Surprisingly, RNAs selected for
      efficient polyadenylation were related by structure rather than sequence.
      Therefore, in the absence of extensive sequence conservation, our results
      strongly suggest that RNA structure is a critical determinant of poly(A) site
      recognition by CPSF and may play a key role in poly(A) site definition.

PMID- 8756654
TI  - Differential activation of target cellular promoters by p53 mutants with impaired
      apoptotic function.
AB  - The p53 tumor suppressor protein is a sequence-specific transcriptional
      activator, a function which contributes to cell cycle arrest and apoptosis
      induced by p53 in appropriate cell types. Analysis of a series of p53 point
      mutants has revealed the potential for selective loss of the ability to
      transactivate some, but not all, cellular p53-responsive promoters. p53 175P and
      p53 181L are tumor-derived p53 point mutants which were previously characterized
      as transcriptionally active. Both mutants retained the ability to activate
      expression of the cyclin-dependent kinase inhibitor p2lcip1/waf1, and this
      activity correlated with the ability to induce a G1 cell cycle arrest. However,
      an extension of this survey to include other p53 targets showed that p53 175P was
      defective in the activation of p53-responsive sequences derived from the bax
      promoter and the insulin-like growth factor-binding protein 3 gene (IGF-BP3)
      promoter, while p53 181L showed loss of the ability to activate a promoter
      containing IGF-BP3 box B sequences. Failure to activate transcription was also
      reflected in the reduced ability of the mutants to bind the p53-responsive DNA
      sequences present in these promoters. These specific defects in transcriptional
      activation correlated with the impaired apoptotic function displayed by these
      mutants, and the results suggest that activation of cell cycle arrest genes by
      p53 can be separated from activation of genes with a role in mediating the p53
      apoptotic response. The cellular response to p53 activation may therefore depend,
      at least in part, on which group of p53-responsive genes become transcriptionally
      activated.

PMID- 8756655
TI  - A mutant p53 that discriminates between p53-responsive genes cannot induce
      apoptosis.
AB  - Human wild-type (wt) p53 can induce apoptosis in transiently transfected H1299
      cells maintained at 37 degrees C, whereas tumor-derived mutant forms of p53 (with
      the mutation Ala-143, His-175, or Trp-248) fail to do so. At 37 degrees C, p53
      with a mutation to Ala at amino acid 143 (p53Ala143) was transcriptionally
      inactive. However, at 32 degrees C, p53Ala143 strongly activated transcription
      from several physiologically relevant p53-responsive promoters, to extents
      similar or greater than that of wt p53. Unexpectedly, p53Ala143 was defective in
      inducing apoptosis in H1299 cells at 32 degrees C. Concomitantly with the loss of
      apoptotic activity, p53Ala143 was found to be deficient in its ability to
      activate transcription from the p53-responsive portions of the Bax and insulin
      like growth factor-binding protein 3 gene promoters. It is proposed that there
      may exist distinct classes of p53-responsive promoters, whose ability to be
      activated by p53 can be regulated differentially. Such differential regulation
      may have functional consequences for the effects of p53 on cell fate.

PMID- 8756656
TI  - Proteolytic disruption of laminin-integrin complexes on muscle cells during
      synapse formation.
AB  - To explore whether a neural modulation of muscle integrins' extracellular ligand
      interactions contributes to synapse induction, we compared the distributions of
      beta1-integrins and basal lamina proteins on Xenopus myotomal myocytes developing
      in culture. beta1-Integrins formed numerous organized aggregates scattered over
      the entire muscle surface, with particularly dense accumulations at specialized
      sites resembling myotendinous and neuromuscular junctions. Integrin aggregates on
      muscle cells differed from those on surrounding fibroblasts and epithelial cells,
      both in their lack of response to cross-linking by multivalent ligands and in
      their consistent association with the cells' own extracellular matrices. Muscle
      integrin clusters were usually associated with congruent basal lamina
      accumulations containing laminin and a heparan sulfate proteoglycan (HSPG),
      sometimes including fibronectin and vitronectin acquired from the surrounding
      medium. Immediately prior to synaptic differentiation, any existing laminin and
      HSPG accumulations along the path of cell contact were eliminated, disrupting
      otherwise stable laminin-integrin complexes. This apparently proteolytic
      modulation of integrins' extracellular ligand interactions was soon followed by
      the accumulation of new congruent accumulations of laminin and HSPG in the
      developing synaptic basal lamina. Combining these results with earlier findings,
      we consider the possibility that postsynaptic differentiation is induced, at
      least in part, by the proteolytic disruption of integrin-ligand complexes at
      sites of nerve-muscle contact.

PMID- 8756657
TI  - Role of the Rab3A-binding domain in targeting of rabphilin-3A to vesicle
      membranes of PC12 cells.
AB  - Rab3A is a small GTPase implicated in the docking of secretory vesicles in
      neuroendocrine cells. A putative downstream target for Rab3A, rabphilin-3A, is
      located exclusively on secretory vesicle membranes. It contains near its C
      terminus two C2 domains that bind Ca2+ in a phospholipid-dependent manner and an
      N-terminal, Rab3A-binding domain that includes a Cys-rich region. We have
      determined that the Cys-rich domain binds two Zn2+ ions and is necessary but not
      sufficient for efficient binding of rabphilin to Rab3A. A minimal Rab3A-binding
      domain consists of residues 45 to 170 of rabphilin. HA1-tagged Rab3A and a green
      fluorescent protein (GFP)-rabphilin fusion were used to examine the roles of
      Rab3A and of rabphilin domains in the subcellular localization of these proteins.
      A Rab3A mutant (T54A) that does not bind rabphifin in vitro colocalized with the
      GFP-rabphilin fusion, indicating that Rab3A targeting is independent of its
      interaction with rabphilin. Deletion of the C2 domains of rabphilin reduced
      membrane association of GFP-rabphilin but did not cause mistargeting of the
      membrane-associated fraction. However, disruption of the zinc fingers, which
      drastically reduced Rab3A binding, did not reduce membrane association. These
      results suggest that the C2 domains are required for efficient membrane
      attachment of rabphilin in PC12 cells and that Rab3A binding may act to target
      the protein to the correct membrane.

PMID- 8756658
TI  - Mutational analysis of Lck in CD45-negative T cells: dominant role of tyrosine
      394 phosphorylation in kinase activity.
AB  - The CD45 tyrosine phosphatase has been reported to activate the src family
      tyrosine kinases Lck and Fyn by dephosphorylating regulatory COOH-terminal
      tyrosine residues 505 and 528, respectively. However, recent studies with CD45- T
      cell lines have found that despite the fact that Lck and Fyn were constitutively
      hyperphosphorylated, the tyrosine kinase activity of both enzymes was actually
      increased. In the present study, phosphoamino acid analysis revealed that the
      increased phosphorylation of Lck in CD45- YAC-1 T cells was restricted to
      tyrosine residues. To understand the relationship between tyrosine
      phosphorylation and Lck kinase activity, CD45- YAC-1 cells were transfected with
      forms of Lck in which tyrosines whose phosphorylation is thought to regulate
      enzyme activity (Tyr-192, Tyr-394, Tyr-505, or both Tyr-394 and Tyr-505) were
      replaced with phenylalanine. While the Y-to-F mutation at position 192 (192-Y-
      >F) had little effect, the 505-Y-->F mutation increased enzymatic activity. In
      contrast, the 394-Y-->F mutation decreased the kinase activity to very low
      levels, an effect that the double mutation, 394-Y-->F and 505Y-->F, could not
      reverse. Phosphopeptide analysis of tryptic digests of Lck from CD45- YAC-1 cells
      revealed that it is hyperphosphorylated on two tyrosine residues, Tyr-505 and, to
      a lesser extent, Tyr-394. The purified and enzymatically active intracellular
      portion of CD45 dephosphorylated Lck Tyr-394 in vitro. These results demonstrate
      that in addition to Tyr-505, CD45 can dephosphorylate Tyr-394, and that in the
      absence of CD45 the hyperphosphorylation of Tyr-394 can cause an increase in the
      kinase activity of Lck despite the inhibitory hyperphosphorylation of Tyr-505.
      Therefore, Lck kinase activity is determined by the balance of activating and
      inhibitory tyrosine phosphorylations that are, in turn, regulated by CD45.

PMID- 8756659
TI  - The POU domain of SCIP/Tst-1/Oct-6 is sufficient for activation of an
      acetylcholine receptor promoter.
AB  - In the PC12 neuroendocrine line, the neuronal nicotinic acetylcholine receptor
      alpha3 gene promoter is activated by SCIP/Tst-1/Oct-6, a POU domain transcription
      factor proposed to be important for regulating the development of specific neural
      cell populations. In this study, we have investigated the SCIP polypeptide
      domains involved in alpha3 promoter activation. The characteristics of activation
      by a chimeric effector in which the GAL4 DNA binding domain was substituted for
      the SCIP POU domain were dramatically different from those of wild-type SCIP. At
      low effector masses, the chimeric polypeptide weakly activated alpha3 in a GAL4
      binding-site-dependent manner but then squelched transcription at higher masses.
      In contrast, wild-type SCIP activation was not modulated by the presence of
      multimerized SCIP binding sites, and squelching was not observed. Analysis of
      wild-type SCIP truncations revealed that deletion of the previously characterized
      SCIP amino-terminal activation domain did not destroy activity of the factor.
      Surprisingly, a truncation expressing nothing more than the POU domain was nearly
      as active as wild-type SCIP. Moreover, cotransfection of a GAL4-VP16 effector
      with an effector expressing just the SCIP POU domain resulted in synergistic
      activation of the promoter. Synergistic activation did not depend on an Sp1 motif
      that is the only functional alpha3 cis element outside the transcription start
      site region. Our results show that the DNA binding domain of a POU factor is
      capable of transcriptional activation probably through protein-protein
      interactions with components of the basal transcription complex.

PMID- 8756660
TI  - Inhibition of c-myc expression induces apoptosis of WEHI 231 murine B cells.
AB  - Treatment of WEHI 231 immature B-lymphoma cells with an antibody against their
      surface immunoglobulin (anti-Ig) induces apoptosis and has been studied
      extensively as a model of B-cell tolerance. Anti-Ig treatment of exponentially
      growing WEHI 231 cells results in an early transient increase in c-myc expression
      that is followed by a decline to below basal levels; this decrease in c-myc
      expression immediately precedes the induction of cell death. Here we have
      modulated NF-kappaB/Rel factor activity, which regulates the rate of c-myc gene
      transcription, to determine whether the increase or decrease in c-Myc-levels
      mediates apoptosis in WEHI 231 cells. Addition of the serine/threonine protease
      inhibitor N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), which blocks the
      normally rapid turnover of the specific inhibitor of NF-kappaB/Rel IkappaBalpha
      in these cells, caused a drop in Rel-related factor binding. TPCK treatment
      resulted in decreased c-myc expression, preventing the usual increase seen
      following anti-Ig treatment. Whereas inhibition of the induction of c-myc
      expression mediated by anti-Ig failed to block apoptosis, reduction of c-myc
      expression in exponentially growing WEHI 231 cells induced apoptosis even in the
      absence of anti-Ig treatment. In WEHI 231 clones ectopically expressing c-Myc,
      apoptosis induced by treatment with TPCK or anti-Ig was significantly diminished
      and cells continued to proliferate. Furthermore, apoptosis of WEHI 231 cells
      ensued following enhanced expression of Mad1, which has been found to reduce
      functional c-Myc levels. These results indicate that the decline in c-myc
      expression resulting from the drop in NF-kappaB/Rel binding leads to activation
      of apoptosis of WEHI 231 B cells.

PMID- 8756661
TI  - Distinct tyrosine phosphorylation sites in ZAP-70 mediate activation and negative
      regulation of antigen receptor function.
AB  - Biochemical and genetic evidence has implicated two families of protein tyrosine
      kinases (PTKs), the Src- and Syk-PTKs, in T- and B-cell antigen receptor
      signaling. ZAP-70 is a member of the Syk-PTKs that associates with the T-cell
      antigen receptor and undergoes tyrosine phosphorylation following receptor
      activation. Three tyrosine residues, Tyr-292, -492, and -493, have been
      identified as sites of phosphorylation following T-cell antigen receptor
      engagement. Utilizing ZAP-70- and Syk-deficient lymphocytes (Syk-DT40 cells), we
      provide biochemical and functional evidence that heterologous trans
      phosphorylation of Tyr-493 by a Src-PTK is required for antigen receptor-mediated
      activation of both the calcium and ras pathways. In contrast, cells expressing
      mutations at Tyr-292 or -492 demonstrate hyperactive T- and B-cell antigen
      receptor phenotypes. Thus, phosphorylation of ZAP-70 mediates both activation and
      inactivation of antigen receptor signaling.

PMID- 8756662
TI  - Sex-lethal interacts with splicing factors in vitro and in vivo.
AB  - The Drosophila sex determination gene Sex-lethal controls its own expression and
      the expression of downstream target genes such as transformer by regulating RNA
      splicing. Genetic and molecular studies have established that Sxl requires the
      product of another gene, snf, to autoregulate the splicing of its own
      transcripts. snf has recently been shown to encode a Drosophila U1 and U2 small
      nuclear ribonucleoprotein particle protein. In the work reported here, we
      demonstrate that the Sxl and Snf proteins can interact directly in vitro and that
      these two proteins are part of an RNase-sensitive complex in vivo which can be
      immunoprecipitated with the Sxl antibody. Unlike bulk Snf protein, which
      sediments slowly in sucrose gradients, the Snf protein associated with Sxl is in
      a large, rapidly sedimenting complex. Detailed characterization of the Sxl-Snf
      complexes from cross-linked extracts indicates that these complexes contain
      additional small nuclear ribonucleoprotein particle proteins and the U1 and U2
      small nuclear RNAs. Finally, consistent with the RNase sensitivity of the Sxl-Snf
      complexes, Sxl transcripts can also be immunoprecipitated by Sxl antibodies. On
      the basis of the physical interactions between Sxl and Snf, we present a model
      for Sxl splicing regulation. This model helps explain how the Sxl protein is able
      to promote the sex-specific splicing of Sxl transcripts, utilizing target
      sequences that are distant from the regulated splice sites.

PMID- 8756663
TI  - Amplification of MDM2 inhibits MyoD-mediated myogenesis.
AB  - One obvious phenotype of tumor cells is the lack of terminal differentiation. We
      previously classified rhabdomyosarcoma cell lines as having either a recessive or
      a dominant nondifferentiating phenotype. To study the genetic basis of the
      dominant nondifferentiating phenotype, we utilized microcell fusion to transfer
      chromosomes from rhabdomyosarcoma cells into C2C12 myoblasts. Transfer of a
      derivative chromosome 14 inhibits differentiation. The derivative chromosome 14
      contains a DNA amplification. MDM2 is amplified and overexpressed in these
      nondifferentiating hybrids and in the parental rhabdomyosarcoma. Forced
      expression of MDM2 inhibits MyoD-dependent transcription. Expression of antisense
      MDM2 restores MyoD-dependent transcriptional activity. We conclude that
      amplification and overexpression of MDM2 inhibit MyoD function, resulting in a
      dominant nondifferentiating phenotype.

PMID- 8756664
TI  - E-box sites and a proximal regulatory region of the muscle creatine kinase gene
      differentially regulate expression in diverse skeletal muscles and cardiac muscle
      of transgenic mice.
AB  - Previous analysis of the muscle creatine kinase (MCK) gene indicated that control
      elements required for transcription in adult mouse muscle differed from those
      required in cell culture, suggesting that distinct modes of muscle gene
      regulation occur in vivo. To examine this further, we measured the activity of
      MCK transgenes containing E-box and promoter deletions in a variety of striated
      muscles. Simultaneous mutation of three E boxes in the 1,256-bp MCK 5' region,
      which abolished transcription in muscle cultures, had strikingly different
      effects in mice. The mutations abolished transgene expression in cardiac and
      tongue muscle and caused a reduction in expression in the soleus muscle (a muscle
      with many slow fibers) but did not affect expression in predominantly fast
      muscles: quadriceps, abdominals, and extensor digitorum longus. Other regulatory
      sequences with muscle-type-specific activities were found within the 358-bp 5'
      flanking region. This proximal region conferred relatively strong expression in
      limb and abdominal skeletal muscles but was inactive in cardiac and tongue
      muscles. However, when the 206-bp 5' enhancer was ligated to the 358-bp region,
      high levels of tissue-specific expression were restored in all muscle types.
      These results indicate that E boxes and a proximal regulatory region are
      differentially required for maximal MCK transgene expression in different
      striated muscles. The overall results also imply that within skeletal muscles,
      the steady-state expression of the MCK gene and possibly other muscle genes
      depends on transcriptional mechanisms that differ between fast and slow fibers as
      well as between the anatomical and physiological attributes of each specific
      muscle.

PMID- 8756665
TI  - The GTPase-activating protein n-chimaerin cooperates with Rac1 and Cdc42Hs to
      induce the formation of lamellipodia and filopodia.
AB  - n-Chimaerin is a GTPase-activating protein (GAP) mainly for Rac1 and less so for
      Cdc42Hs in vitro. The GAP activity of n-chimaerin is regulated by phospholipids
      and phorbol esters. Microinjection of Rac1 and Cdc42Hs into mammalian cells
      induces formation of the actin-based structures lamellipodia and filopodia,
      respectively, with the former being prevented by coinjection of the chimaerin GAP
      domain. Strikingly, microinjection of the full-length n-chimaerin into
      fibroblasts and neuroblastoma cells induces the simultaneous formation of
      lamellipodia and filopodia. These structures undergo cycles of dissolution and
      formation, resembling natural morphological events occurring at the leading edge
      of fibroblasts and neuronal growth cones. The effects of n-chimaerin on formation
      of lamellipodia and filopodia were inhibited by dominant negative Rac1(T17N) and
      Cdc42Hs(T17N), respectively. n-Chimaerin's effects were also inhibited by
      coinjection with Rho GDP dissociation inhibitor or by treatment with phorbol
      ester. A mutant n-chimaerin with no GAP activity and impaired p21 binding was
      ineffective in inducing morphological changes, while a mutant lacking GAP
      activity alone was effective. Microinjected n-chimaerin colocalized in situ with
      F-actin. Taken together, these results suggest that n-chimaerin acts
      synergistically with Rac1 and Cdc42Hs to induce actin-based morphological changes
      and that this action involves Rac1 and Cdc42Hs binding but not GAP activity.
      Thus, GAPs may have morphological functions in addition to downregulation of
      GTPases.

PMID- 8756666
TI  - Physical interactions among Mcm proteins and effects of Mcm dosage on DNA
      replication in Saccharomyces cerevisiae.
AB  - Mcm2, Mcm3, and Mcm5/Cdc46 are conserved proteins essential for the initiation of
      DNA synthesis at replication origins in Saccharomyces cerevisiae. The
      accumulation of these proteins in the nucleus before the onset of DNA synthesis
      suggests that they play a role in restricting DNA synthesis to once per cell
      cycle. In this work, we show that Mcm2, Mcm3, and Mcm5 self-interact and interact
      with one another to form complexes. Mcm2 and Mcm3 are abundant proteins, present
      in approximately 4 X 10(4) and 2 X 10(5) copies per cell, respectively. Reducing
      the dosage of Mcm2 by half results in diminished usage of specific replication
      origins. These results together suggest that a significant molar excess of Mcm
      proteins relative to replication origins is required for the proper initiation of
      all replication origins.

PMID- 8756668
TI  - Exon 2-mediated c-myc mRNA decay in vivo is independent of its translation.
AB  - We have previously shown that the steady-state level of c-myc mRNA in vivo is
      primarily controlled by posttranscriptional regulatory mechanisms. To identify
      the sequences involved in this process, we constructed a series of H-2/myc
      transgenic lines in which various regions of the human c-MYC gene were placed
      under the control of the quasi-ubiquitous H-2K class I regulatory sequences. We
      demonstrated that the presence of one of the two coding exons, exon 2 or exon 3,
      is sufficient to confer a level of expression of transgene mRNA similar to that
      of endogenous c-myc in various adult tissues as well as after partial hepatectomy
      or after protein synthesis inhibition. We now focus on the molecular mechanisms
      involved in modulation of expression of mRNAs containing c-myc exon 2 sequences,
      with special emphasis on the coupling between translation and c-myc mRNA
      turnover. We have undertaken an analysis of expression, both at the mRNA level
      and at the protein level, of new transgenic constructs in which the translation
      is impaired either by disruption of the initiation codon or by addition of stop
      codons upstream of exon 2. Our results show that the translation of c-myc exon 2
      is not required for regulated expression of the transgene in the different
      situations analyzed, and therefore they indicate that the mRNA destabilizing
      function of exon 2 is independent of translation by ribosomes. Our investigations
      also reveal that, in the thymus, some H-2/myc transgenes express high levels of
      mRNA but low levels of protein. Besides the fact that these results suggest the
      existence of tissue-specific mechanisms that control c-myc translatability in
      vivo, they also bring another indication of the uncoupling of c-myc mRNA
      translation and degradation.

PMID- 8756667
TI  - Characterization of NERF, a novel transcription factor related to the Ets factor
      ELF-1.
AB  - We have cloned the gene for a novel Ets-related transcription factor, new Ets
      related factor (NERF), from human spleen, fetal liver, and brain. Comparison of
      the deduced amino acid sequence of NERF with those of other members of the Ets
      family reveals that the level of homology to ELF-1, which is involved in the
      regulation of several T- and B-cell-specific genes, is highest. Homologies are
      clustered in the putative DNA binding domain in the middle of the protein, a
      basic domain just upstream of this domain, and several shorter stretches of
      homology towards the amino terminus. The presence of two predominant NERF
      transcripts in various fetal and adult human tissues is due to at least three
      alternative splice products, NERF-1a, NERF-1b, and NERF-2, which differ in their
      amino termini and their expression in different tissues. Only NERF-2 and ELF-1,
      and not NERF-1a and NERF-1b, function as transcriptional activators of the lyn
      and blk gene promoters, although all isoforms of NERF bind with affinities
      similar to those of ELF-1 to a variety of Ets binding sites in, among others, the
      blk, lck, lyn, mb-1, and immunoglobulin H genes and are expressed at similar
      levels. Since NERF and ELF-1 are coexpressed in B and T cells, both might be
      involved in the regulation of the same genes.

PMID- 8756669
TI  - Stable episomal maintenance of yeast artificial chromosomes in human cells.
AB  - Plasmids carrying the Epstein-Barr virus origin of plasmid replication (oriP)
      have been shown to replicate autonomously in latently infected human cells (J.
      Yates, N. Warren, D. Reisman, and B. Sugden, Proc. Natl. Acad. Sci. USA 81:3806
      3810, 1984). We demonstrate that addition of this domain is sufficient for stable
      episomal maintenance of yeast artificial chromosomes (YACs), up to at least 660
      kb, in human cells expressing the viral protein EBNA-1. To better approximate the
      latent viral genome, YACs were circularized before addition of the oriP domain by
      homologous recombination in yeast cells. The resulting OriPYACs were maintained
      as extrachromosomal molecules over long periods in selection; a 90-kb OriPYAC was
      unrearranged in all cell lines analyzed, whereas the intact form of a 660-kb
      molecule was present in two of three cell lines. The molecules were also
      relatively stable in the absence of selection. This finding indicates that the
      oriP-EBNA-1 interaction is sufficient to stabilize episomal molecules of at least
      660 kb and that such elements do not undergo rearrangements over time.
      Fluorescence in situ hybridization analysis demonstrated a close association of
      OriPYACs, some of which were visible as pairs, with host cell chromosomes,
      suggesting that the episomes replicate once per cell cycle and that stability is
      achieved by attachment to host chromosomes, as suggested for the viral genome.
      The wide availability of YAC libraries, the ease of manipulation of cloned
      sequences in yeast cells, and the episomal stability make OriPYACs ideal for
      studying gene function and control of gene expression.

PMID- 8756670
TI  - Rat embryo fibroblasts immortalized with simian virus 40 large T antigen undergo
      senescence upon its inactivation.
AB  - Introduction of simian virus 40 T antigen into rodent fibroblasts gives rise to
      cells that can proliferate indefinitely but are dependent upon it for maintenance
      of their growth once the normal mitotic life span has elapsed. Inactivation of T
      antigen in these immortalized cells causes rapid and irreversible cessation of
      growth. To determine whether this growth arrest is associated with entry into
      senescence, we have undertaken a genetic and biological analysis of conditionally
      immortal (tsa) cell lines derived by immortalizing rat embryo fibroblasts with
      the thermolabile tsA58 T antigen. This analysis has identified the following
      parallels between the tsa cells after inactivation of T antigen and senescent rat
      embryo fibroblasts: (i) growth arrest is irreversible; (ii) it occurs in G1 as
      well as G2; (iii) the G1 block can be partially overcome by stimulation with 20%
      fetal calf serum, but the G2 block cannot be overcome; (iv) 20% fetal calf serum
      induces c-fos, but c-myc is unaltered; and (v) fibronectin and
      p21(Waf1/Cip1/Sdi1) are upregulated upon growth arrest. These results suggest
      that T-antigen-immortalized fibroblasts are committed to undergo senescence but
      are prevented from undergoing this process by T antigen. Inactivation of T
      antigen removes this block and results in senescence of the cells. Thus, these
      cell lines may represent a powerful system for study of the molecular basis of
      entry into senescence.

PMID- 8756671
TI  - A DEAD-box-family protein is required for nucleocytoplasmic transport of yeast
      mRNA.
AB  - An enormous variety of primary and secondary mRNA structures are compatible with
      export from the nucleus to the cytoplasm. Therefore, there seems to be a
      mechanism for RNA export which is independent of sequence recognition. There
      nevertheless is likely to be some relatively uniform mechanism which allows
      transcripts to be packaged as ribonucleoprotein particles, to gain access to the
      periphery of the nucleus and ultimately to translocate across nuclear pores. To
      study these events, we and others have generated temperature-sensitive recessive
      mRNA transport (mtr) mutants of Saccharomyces cerevisiae which accumulate
      poly(A)+ RNA in the nucleus at 37 degrees C. Several of the corresponding genes
      have been cloned. Upon depletion of one of these proteins, Mtr4p, conspicuous
      amounts of nuclear poly(A)+ RNA accumulate in association with the nucleolus.
      Corresponding dense material is also seen by electron microscopy. MTR4 is
      essential for growth and encodes a novel nuclear protein with a size of
      approximately 120 kDa. Mtr4p shares characteristic motifs with DEAD-box RNA
      helicases and associates with RNA. It therefore may well affect RNA conformation.
      It shows extensive homology to a human predicted gene product and the yeast
      antiviral protein Ski2p. Critical residues of Mtr4p, including the mtr4-1 point
      mutation, have been identified. Mtr4p may serve as a chaperone which translocates
      or normalizes the structure of mRNAs in preparation for export.

PMID- 8756672
TI  - Characterization of the nuclear export signal of human T-cell lymphotropic virus
      type 1 Rex reveals that nuclear export is mediated by position-variable
      hydrophobic interactions.
AB  - We previously determined that amino acids 64 to 120 of human T-cell lymphotropic
      virus type 1 (HTLV-1) Rex can restore the function of an effector domain mutant
      of human immunodeficiency virus type 1 (HIV-1) Rev (T. J. Hope, B. L. Bond, D.
      McDonald, N. P. Klein, and T. G. Parslow, J. Virol. 65:6001-6007, 1991). In this
      report, we (i) identify and characterize a position-independent 17-amino-acid
      region of HTLV-1 Rex that fully complements HIV-1 Rev effector domain mutants and
      (ii) show that this 17-amino-acid region and specific hydrophobic substitutions
      can serve as nuclear export signals. Mutagenesis studies revealed that four
      leucines within the minimal region were essential for function. Alignment of the
      minimal Rex region with the HIV-1 Rev effector domain suggested that the position
      of some of the conserved leucines is flexible. We found two of the leucines could
      each occupy one of two positions within the context of the full-length HTLV-1 Rex
      protein and maintain function. The idea of flexibility within the Rex effector
      domain was confirmed and extended by identifying functional substitutions by
      screening a library of effector domain mutants in which the two regions of
      flexibility were randomized. Secondly, the functional roles of the minimal Rex
      effector domain and hydrophobic substitutions were independently confirmed by
      demonstrating that these effector domains could serve as nuclear export signals
      when conjugated with bovine serum albumin. Nuclear export of the wild-type Rex
      conjugates was temperature dependent and sensitive to wheat germ agglutinin and
      was blocked by a 20-fold excess of unlabeled conjugates. Together, these studies
      reveal that position-variable hydrophobic interactions within the HTLV-1 Rex
      effector domain mediate nuclear export function.

PMID- 8756673
TI  - Surprising deficiency of CENP-B binding sites in African green monkey alpha
      satellite DNA: implications for CENP-B function at centromeres.
AB  - Centromeres of mammalian chromosomes are rich in repetitive DNAs that are
      packaged into specialized nucleoprotein structures called heterochromatin. In
      humans, the major centromeric repetitive DNA, alpha-satellite DNA, has been
      extensively sequenced and shown to contain binding sites for CENP-B, an 80-kDa
      centromeric autoantigen. The present report reveals that African green monkey
      (AGM) cells, which contain extensive alpha-satellite arrays at centromeres,
      appear to lack the well-characterized CENP-B binding site (the CENP-B box). We
      show that AGM cells express a functional CENP-B homolog that binds to the CENP-B
      box and is recognized by several independent anti-CENP-B antibodies. However,
      three independent assays fail to reveal CENP-B binding sites in AGM DNA. Methods
      used include a gel mobility shift competition assay using purified AGM alpha
      satellite, a novel kinetic electrophoretic mobility shift assay competition
      protocol using bulk genomic DNA, and bulk sequencing of 76 AGM alpha-satellite
      monomers. Immunofluorescence studies reveal the presence of significant levels of
      CENP-B antigen dispersed diffusely throughout the nuclei of interphase cells.
      These experiments reveal a paradox. CENP-B is highly conserved among mammals, yet
      its DNA binding site is conserved in human and mouse genomes but not in the AGM
      genome. One interpretation of these findings is that the role of CENP-B may be in
      the maintenance and/or organization of centromeric satellite DNA arrays rather
      than a more direct involvement in centromere structure.

PMID- 8756674
TI  - Centromere protein B of African green monkey cells: gene structure, cellular
      expression, and centromeric localization.
AB  - Centromere protein B (CENP-B) is a centromeric DNA-binding protein which
      recognizes a 17-bp sequence (CENP-B box) in human and mouse centromeric satellite
      DNA. The African green monkey (AGM) is phylogenetically closer to humans than
      mice and is known to contain large amounts of alpha-satellite DNA, but there has
      been no report of CENP-B boxes or CENP-B in the centromere domains of its
      chromosomes. To elucidate the AGM CENP-B-CENP-B box interaction, we have analyzed
      the gene structure, expression, biochemical properties, and centromeric
      localization of its CENP-B. The amino acid sequence deduced from the cloned AGM
      CENP-B gene was established to be highly homologous to that of human and mouse
      CENP-B. In particular, the DNA binding and homodimer formation domains
      demonstrated 100% identity to their human and mouse counterparts. Immunoblotting
      and DNA mobility shift analyses revealed CENP-B to be expressed in AGM cell
      lines. As predicted from the gene structure, the AGM CENP-B in the cell extracts
      exhibited the same DNA binding specificity and homodimer forming activity as
      human CENP-B. By indirect immunofluorescent staining of AGM mitotic cells with
      anti-CENP-B antibodies, a centromere-specific localization of AGM CENP-B could be
      demonstrated. We also isolated AGM alpha-satellite DNA with a CENP-B box-like
      sequence with CENP-B affinity. These results not only prove that CENP-B
      functionally persists in AGM cells but also suggest that the AGM genome contains
      the recognition sequences for CENP-B (CENP-B boxes with the core recognition
      sequence or CENP-B box variants) in centromeric satellite DNA.

PMID- 8756675
TI  - p53 plays a regulatory role in differentiation and apoptosis of central nervous
      system-associated cells.
AB  - This study demonstrated the involvement of the tumor suppressor protein p53 in
      differentiation and programmed cell death of neurons and oligodendrocytes, two
      cell types that leave the mitotic cycle early in development and undergo massive
      scale cell death as the nervous system matures. We found that primary cultures of
      rat oligodendrocytes and neurons, as well as of the neuronal PC12
      pheochromocytoma cell line, constitutively express the p53 protein. At critical
      points in the maturation of these cells in vitro, the subcellular localization of
      p53 changes: during differentiation it appears mainly in the nucleus, whereas in
      mature differentiated cells it is present mainly in the cytoplasm. These
      subcellular changes were correlated with changes in levels of immunoprecipitated
      p53. Infection of cells with a recombinant retrovirus encoding a C-terminal p53
      miniprotein (p53 DD), previously shown to act as a dominant negative inhibitor of
      endogenous wild-type p53 activity, inhibited the differentiation of
      oligodendrocytes and of PC12 cells and protected neurons from spontaneous
      apoptotic death. These findings suggest that p53, upon receiving appropriate
      signals, is recruited into the nucleus, where it plays a regulatory role in
      directing primary neurons', oligodendrocytes, and PC12 cells toward either
      differentiation or apoptosis in vitro.

PMID- 8756676
TI  - Protein-protein and protein-DNA interaction regions within the DNA end-binding
      protein Ku70-Ku86.
AB  - DNA ends are generated during double-strand-break repair and recombination. A p70
      p86 heterodimer, Ku, accounts for the DNA end binding activity in eukaryotic cell
      extracts. When one or both subunits of Ku are missing, mammalian cells are
      deficient in double-strand-break repair and in specialized recombination, such as
      V(D)J recombination. Little is known of which regions of Ku70 and Ku86 bind to
      each other to form the heterodimeric complex or of which regions are important
      for DNA end binding. We have done genetic and biochemical studies to examine the
      domains within the two subunits important for protein assembly and for DNA end
      binding. We found that the C-terminal 20-kDa region of Ku70 and the C-terminal 32
      kDa region of Ku86 are important for subunit-subunit interaction. For DNA
      binding, full-length individual subunits are inactive, indicating that
      heterodimer assembly precedes DNA binding. DNA end binding activity by the
      heterodimer requires the C-terminal 40-kDa region of Ku70 and the C-terminal 45
      kDa region of Ku86. Leucine zipper-like motifs in both subunits that have been
      suggested as the Ku70-Ku86 interaction domains do not appear to be the sites of
      such interaction because these are dispensable for both assembly and DNA end
      binding. On the basis of these studies, we have organized Ku70 into nine sequence
      regions conserved between Saccharomyces cerevisiae, Drosophila melanogaster,
      mice, and humans; only the C-terminal three regions are essential for assembly
      (amino acids [aa] 439 to 609), and the C-terminal four regions appear to be
      essential for DNA end binding (aa 254 to 609). Within the minimal active fragment
      of Ku86 necessary for subunit interaction (aa 449 to 732) and DNA binding (aa 334
      to 732), a proline-rich region is the only defined motif.

PMID- 8756677
TI  - Sst2, a negative regulator of pheromone signaling in the yeast Saccharomyces
      cerevisiae: expression, localization, and genetic interaction and physical
      association with Gpa1 (the G-protein alpha subunit).
AB  - Sst2 is the prototype for the newly recognized RGS (for regulators of G-protein
      signaling) family. Cells lacking the pheromone-inducible SST2 gene product fail
      to resume growth after exposure to pheromone. Conversely, overproduction of Sst2
      markedly enhanced the rate of recovery from pheromone-induced arrest in the long
      term halo bioassay and detectably dampened signaling in a short-term assay of
      pheromone response (phosphorylation of Ste4, Gbeta subunit). When the GPA1 gene
      product (Galpha subunit) is absent, the pheromone response pathway is
      constitutively active and, consequently, growth ceases. Despite sustained
      induction of Sst2 (observed with specific anti-Sst2 antibodies), gpa1delta
      mutants remain growth arrested, indicating that the action of Sst2 requires the
      presence of Gpa1. The N-terminal domain (residues 3 to 307) of Sst2 (698
      residues) has sequence similarity to the catalytic regions of bovine GTPase
      activating protein and human neurofibromatosis tumor suppressor protein; segments
      in the C-terminal domain of Sst2 (between residues 417 and 685) are homologous to
      other RGS proteins. Both the N- and C-terminal domains were required for Sst2
      function in vivo. Consistent with a role for Sst2 in binding to and affecting the
      activity of Gpa1, the majority of Sst2 was membrane associated and colocalized
      with Gpa1 at the plasma membrane, as judged by sucrose density gradient
      fractionation. Moreover, from cell extracts, Sst2 could be isolated in a complex
      with Gpa1 (expressed as a glutathione S-transferase fusion); this association
      withstood the detergent and salt conditions required for extraction of these
      proteins from cell membranes. Also, SST2+ cells expressing a GTPase-defective
      GPA1 mutant displayed an increased sensitivity to pheromone, whereas sst2 cells
      did not. These results demonstrate that Sst2 and Gpa1 interact physically and
      suggest that Sst2 is a direct negative regulator of Gpa1.

PMID- 8756679
TI  - Three of four cysteines, including that responsible for substrate activation, are
      ionized at pH 6.0 in yeast pyruvate decarboxylase: evidence from Fourier
      transform infrared and isoelectric focusing studies.
AB  - Oligonucleotide-directed site-specific mutagenesis was carried out on pyruvate
      decarboxylase (EC 4.1.1.1) from Saccharomyces cerevisiae at three of the four
      cysteines (152, 221, and 222), the fourth (69) being buried according to X-ray
      crystallographic results [Arjunan et al. (1996) J. Mol. Biol. 256, 590-600]. All
      of the variants still retained significant activity, and all could be purified to
      homogeneity. FT-IR experiments were run on the C221S, C222S, C221S/C222S and
      C152A variants, as well as on the wild-type enzyme. There is a band present at
      2557 cm-1 in the spectra of all variants and the wild-type enzyme, except in the
      spectrum of the C152A variant. This frequency is appropriate to a cysteine S-H
      stretching mode. It was therefore concluded that C152 is the only undissociated
      cysteine on the enzyme at pH 6.0, the pH optimum of this enzyme, whereas C221,
      C222, and C69 are all ionized. Isoelectric focusing experiments were carried out
      on all of these variants, as well as on the H92A variant (H92 is across the
      domain divide on the alpha domain, from C221 located on the beta domain). The
      variation in isoelectric points deduced from the data was consistent with removal
      of negative charges concomitant with the C221S, C222S, and C221S/C222S
      substitutions and removal of a positive charge with the H92A substitution when
      compared to that of the wild-type enzyme. The results of these two types of
      experiments are in good accord and suggest that the site of substrate activation
      at C221 [Baburina et al. (1994) Biochemistry 33, 5630-5635] is comprised of a
      Cys221S- +HHis92 ion pair, not unlike that found in papain and glyceraldehyde-3
      phosphate dehydrogenase. This finding suggests that the regulatory site of this
      enzyme has been optimized for nucleophilic reactivity between the thiolate of
      C221 and the keto carbon of the 2-oxoacid.

PMID- 8756680
TI  - The CD4 determinant for downregulation by HIV-1 Nef directly binds to Nef.
      Mapping of the Nef binding surface by NMR.
AB  - Using heteronuclear NMR spectroscopy, we demonstrate that a 13-residue peptide
      (MS-QIKRLLSEKKT) from the cytoplasmic tail of CD4 binds to Nef protein. This part
      of CD4 is critical for downregulation of CD4 by HIV-1 Nef [Aiken et al. (1994)
      Cell 76, 853-864]. We show that a control peptide without the central dileucine
      does not bind to Nef. The dependence of Nef 1H and 15N amide chemical shifts on
      peptide concentration indicates that the binding is in the fast chemical exchange
      limit, with a dissociation constant Kd of approximately 1 mM. The peptide binding
      site has been mapped onto the previously determined solution structure of HIV-1
      Nef [Grzesiek et al. (1996) Nat. Struct. Biol. 3, 340-345] on the basis of
      peptide-induced chemical shift changes. It comprises amino acids W57, L58, E59,
      G95, G96, L97, R106, and L110. When Nef is complexed to the SH3 domain of Hck
      tyrosine protein kinase, the peptide binds to the same site on Nef but with
      slightly higher affinity (Kd approximately 0.5 mM). This indicates that the
      binding of CD4 and Hck SH3 to Nef are two compatible and slightly cooperative
      events.

PMID- 8756678
TI  - Human fibroblast commitment to a senescence-like state in response to histone
      deacetylase inhibitors is cell cycle dependent.
AB  - Human diploid fibroblasts (HDF) complete a limited number of cell divisions
      before entering a growth arrest state that is termed replicative senescence. Two
      histone deacetylase inhibitors, sodium butyrate and trichostatin A, dramatically
      reduce the HDF proliferative life span in a manner that is dependent on one or
      more cell doublings in the presence of these agents. Cells arrested and
      subsequently released from histone deacetylase inhibitors display markers of
      senescence and exhibit a persistent G1 block but remain competent to initiate a
      round of DNA synthesis in response to simian virus 40 T antigen. Average telomere
      length in prematurely arrested cells is greater than in senescent cells,
      reflecting a lower number of population doublings completed by the former. Taken
      together, these results support the view that one component of HDF senescence
      mimics a cell cycle-dependent drift in differentiation state and that propagation
      of HDF in histone deacetylase inhibitors accentuates this component.

PMID- 8756681
TI  - A host-guest set of triple-helical peptides: stability of Gly-X-Y triplets
      containing common nonpolar residues.
AB  - Host-guest peptide sets have been useful in evaluating the propensity of
      different amino acids to adopt an alpha-helical or beta-sheet form, and this
      concept is applied here to the triple-helical conformation. A set of host-guest
      peptides of the form acetyl-(Gly-Pro-Hyp)3-Gly-X-Y-(Gly-Pro-Hyp)4-Gly-GlyCONH2
      was designed to evaluate the contribution of an isolated Gly-X-Y triplet to
      triple-helix stability in a defined environment. Peptides were synthesized to
      include guest triplets with the X and Y positions occupied by the most common
      nonpolar residues found in collagen: Pro (X position) and Hyp (Y position); Ala;
      Leu, the most frequent hydrophobic residue; and Phe, the only commonly occurring
      aromatic residue. The guest triplets of the 12 peptides synthesized represent 35%
      of the sequence found in the alpha 1 chain of type I collagen. All peptides
      formed stable triple-helical structures, and the peptides showed a range of
      thermal stabilities (Tm = 21-44 degrees C), depending on the identity of the
      guest triplet. Thermodynamic calculations indicate these peptides have a range of
      free energy values (delta delta G = 9 kcal/mol) and suggest that favorable
      entropy is the dominant factor in increased stability. Replacement of Ala by Leu
      in the X position did not affect the thermal stability, while an Ala to Leu
      change in the Y position was destabilizing. These data provide experimental
      evidence that hydrophobic residues do not stabilize the triple helical
      conformation. Although Leu and Phe are found almost exclusively in the X position
      in collagens, peptides with Leu and Phe in the Y position formed stable triple
      helices. This supports the hypothesis that the X positional preference of these
      residues relates to their increased potential for intermolecular hydrophobic
      interactions rather than their destabilization of the triple-helical molecule.
      These studies establish the utility of host-guest peptides in defining a scale of
      triple-helix propensities and in clarifying the interactions stabilizing the
      triple-helical conformation.

PMID- 8756682
TI  - Structure and importance of the dimerization domain in elongation factor Ts from
      Thermus thermophilus.
AB  - Elongation factor Ts (EF-Ts) functions as a nucleotide-exchange factor by binding
      elongation factor Tu (EF-Tu) and accelerating the GDP dissociation from EF-Tu;
      thus EF-Ts promotes the transition of EF-Tu from the inactive GDP form to the
      active GTP form. Thermus thermophilus EF-Ts exists as a stable dimer in solution
      which binds two molecules of EF-Tu to form a (EF-Tu.EF-Ts)2 heterotetramer. Here
      we report the crystal structure of the dimerization domain of EF-Ts from T.
      thermophilus refined to 1.7 A resolution. A three-stranded antiparallel beta
      sheet from each subunit interacts to form a beta-sandwich that serves as an
      extensive dimer interface tethered by a disulfide bond. This interface is
      distinctly different from the predominantly alpha-helical one that stabilizes the
      EF-Ts dimer from Escherichia coli [Kawashima, T., et al. (1996) Nature 379, 511
      518]. To test whether the homodimeric form of T. thermophilus EF-Ts is necessary
      for catalyzing nucleotide exchange, the present structure was used to design
      mutational changes within the dimer interface that disrupt the T. thermophilus EF
      Ts dimer but not the tertiary structure of the subunits. Surprisingly, EF-Ts
      monomers created in this manner failed to catalyze nucleotide exchange in EF-Tu,
      indicating that, in vitro. T. thermophilus EF-Ts functions only as a homodimer.

PMID- 8756683
TI  - Human immunodeficiency virus protease ligand specificity conferred by residues
      outside of the active site cavity.
AB  - To gain greater understanding of the structural basis of human immunodeficiency
      virus (HIV) protease ligand specificity, we have crystallized and determined the
      structures of the HIV-1 protease (Val32Ile, Ile47Val, Val82Ile) triple mutant and
      simian immunodeficiency virus (SIV) protease in complex with SB203386, a
      tripeptide analogue inhibitor containing a C-terminal imidazole substituent as an
      amide bond isostere. SB203386 is a potent inhibitor of HIV-1 protease (Ki = 18
      nM) but shows decreased inhibition of the HIV-1 protease (Val32Ile, Ile47Val,
      Val82Ile) triple mutant (Ki = 112 nM) and SIV protease (Ki = 960 nM). Although
      SB203386 binds in the active site cavity of the triple mutant in a similar
      fashion to its binding to the wild-type HIV-1 protease [Abdel-Meguid et al.
      (1994) Biochemistry 33, 11671], it binds to SIV protease in an unexpected mode
      showing two inhibitor molecules each binding to half of the active site.
      Comparison of these two structures and that of the wild-type HIV-1 protease bound
      to SB203386 reveals that HIV protease ligand specificity is imparted by residues
      outside of the catalytic pocket, which causes subtle changes in its shape.
      Furthermore, this work illustrates the importance of structural studies in order
      to understand the structure-activity relationship (SAR) between related enzymes.

PMID- 8756684
TI  - Complexes formed between calmodulin and the antagonists J-8 and TFP in solution.
AB  - The binding of the antagonists N-(8-aminooctyl)-5-iodonaphthalene-1-sulfonamide
      (J-8) and trifluoperazine (TFP) to intact calcium-saturated bovine calmodulin
      (CaM) and also of J-8 to the C-terminal domain (tr2c) has been investigated.
      Using a combination of NMR methods, including NOESY data, mobility measurements,
      and chemical shift and line-shape analysis, we show that the primary interaction
      between J-8 and tr2c is between the naphthalene ring of the antagonist and the
      hydrophobic pocket of the protein, similar to the binding of the hydrophobic side
      chain residues of calmodulin target peptides. Comparison of the mobility of the
      drug, the intensity and pattern of intermolecular NOESY cross-peaks, and chemical
      shift changes shows that there is no significant change in the binding mode in J
      8. CaM compared to J-8.tr2c, with one molecule binding to each domain. In
      particular, we find that the mobility of the aliphatic amino "tail" of J-8
      remains highly mobile in both systems. This contrasts with the notion that the
      tail may bridge between the two domains to give a "globular" form of CaM. We also
      show that TFP induces very similar shift changes to J-8 and that the
      stoichiometry of the major binding event in all three cases is one drug molecule
      per domain. It also appears that secondary binding sites for the drug molecules
      are present in all three systems.

PMID- 8756685
TI  - Structural and mutational analysis of affinity-inert contact residues at the
      growth hormone-receptor interface.
AB  - Mutational studies have shown that over two-thirds of the contact side chains at
      the human growth hormone (hGH)-receptor interface have little or no impact on
      binding affinity when converted to alanine [Cunningham, B. C., & Wells, J. A.
      (1993) J. Mol. Biol. 234, 554-563; Clackson, T., & Wells, J. A. (1995) Science
      267. 383-386]. Herein, three of the most buried, yet functionally inert, residues
      on hGH (F25, Y42, and Q46) have been simultaneously mutated to alanine. Binding
      kinetics of the triple-alanine mutant shows that neither association nor
      dissociation rates are significantly affected and only slight, local disorder is
      seen in the crystal structure. However, large and compensating changes were
      observed in the enthalpy and entropy of binding as determined by isothermal
      titration calorimetry. The triple-alanine mutant bound with a more favorable
      enthalpy (delta H = -12.2 +/- 0.7 kcal/mol) and corresponding less favorable
      entropy [delta S = -2.3 +/- 2.4 cal/(mol.K)] compared to the wild-type
      interaction [delta H = -9.4 +/- 0.3 kcal/mol; delta S = 7.7 +/- 1.2 cal/(mol.K)].
      Dissection of the triple-alanine mutant into the single F25A and double Y42A/Q46A
      mutant showed that the more favorable enthalpy was derived from the removal of
      the F25 side chain on helix-1 of the hormone. The delta Cp values for both the
      triple-alanine mutant [-927 +/- 10 cal/(mol.K)] and the individual mutants were
      significantly more negative than the delta Cp for the wild-type interaction [-767
      +/- 34 cal/(mol.K)]. Such negative delta Cp values are consistent with the
      proposal that the hydrophobic effect is the primary contributor to the free
      energy of binding at this protein-protein interface. These results show that
      multiple-alanine mutations at contact residues may not affect binding kinetics,
      affinity, or global structure; however, they can produce local structural changes
      and can cause large compensating effects on the heat and entropy of binding.
      These studies emphasize that one cannot infer binding free energy from the
      existence of contacts alone and further support the notion that only a small set
      of contacts are crucial for the human growth hormone-receptor interaction.

PMID- 8756686
TI  - Conformational transitions in p21ras and in its complexes with the effector
      protein Raf-RBD and the GTPase activating protein GAP.
AB  - 31P NMR revealed that the complex of p21ras with the GTP analog GppNHp.Mg2+
      exists in two conformational states, states 1 and 2. In wild-type p21ras the
      equilibrium constant K1(12) between the two states is 1.09. The population of
      these states is different for various mutants but independent of temperature. The
      activation enthalpy delta H ++ and activation entropy delta S ++ for the
      conformational transitions were determined by full-exchange matrix analysis for
      wild-type p21ras and p21ras(S65P). For the wild-type protein one obtains delta H
      ++ = 89 +/- 2 kJ mol-1 and delta S ++ = 102 +/- 20 J mol-1 K-1 and for the mutant
      protein delta H ++ = 93 +/- 7 kJ mol-1 and delta S ++ = 138 +/- 30 J mol-1 K-1.
      The study of various p21ras mutants suggests that the two states correspond to
      different conformations of loop L2, with Tyr-32 in two different positions
      relative to the bound nucleotide. High-field EPR at 95 GHz suggest that the
      observed conformational transition does not directly influence the coordination
      sphere of the protein-bound metal ion. The influence of this transition on loop
      L4 was studied by 1H NMR with mutants E62H and E63H. There was no indication that
      L4 takes part in the transition described in L2, although a reversible
      conformational change could be induced by decreasing the pH value. The exchange
      between the two states is slow on the NMR time scale (< 10 s-1): at approximately
      pH 5 the population of the two states is equal. The interaction of p21ras
      triphosphate complexes with the Ras-binding domain (RBD) of the effector protein
      c-Raf-1, Raf-RBD, and with the GTPase activating protein GAP was studied by 31P
      NMR spectroscopy. In complex with Raf-RBD the second conformation of p21ras
      (state 2) is stabilized. In this conformation Tyr-32 is located in close
      proximity to the phosphate groups of the nucleotide, and the beta-phosphate
      resonance is shifted upfield by 0.7 ppm. Spectra obtained in the presence of GAP
      suggest that in the ground state GAP does not interact directly with the
      nucleotide bound to p21ras and does not induce larger conformational changes in
      the neighborhood of the nucleotide. The experimental data are consistent with a
      picture where GAP accelerates the exchange process between the two states and
      simultaneously increases the population of state 1 at higher temperature.

PMID- 8756687
TI  - Characterization of gamma-carboxyglutamic acid residue 21 of human factor IX.
AB  - We investigated the functional role of gamma-carboxyglutamic acid (Gla) residue
      21 of human factor IX, using site-directed mutagenesis to change the glutamic
      acid residue to aspartic acid (FIX21D). FIX21D had reduced activity in an
      activated partial thromboplastin time (aPTT) assay and was activated by factor
      XIa more slowly than wild-type factor IX (FIXwt). FIX21D underwent normal, two
      stage calcium-dependent intrinsic fluorescence quenching, indicating that a
      folding event similar to that seen in FIXwt occurred upon the addition of calcium
      ions. Antibody A-7, which recognizes factor IX-specific residues at positions 33
      40, bound FIX21D as well as FIXwt; however, the calcium-specific monoclonal
      antibody, JK-IX-2, whose epitope includes residues 1 and 22, did not recognize
      FIX21D. FIX21D bound phosphatidylserine/phosphatidylcholine (PS/PC) vesicles with
      Kd approximately 10-fold greater than FIXwt, as measured by a fluorescence light
      scattering assay. Finally, although FIXwt binds endothelial cells with a Kd of
      2.8 nM, FIX21D did not bind endothelial cells. Molecular modeling simulations of
      FIXwt and FIX21D indicate that mutating Gla 21 to Asp causes structural changes
      in residues 3-5 and 8-10, as well as in two exposed calcium ions, consistent with
      the reduced function of FIX21D. Immunological and intrinsic fluorescence
      quenching assays and the molecular dynamics simulations suggest normal folding in
      the C-terminal region of the Gla domain. Thus we hypothesize the FIX21D has
      reduced JK-IX-2 and phospholipid and endothelial cell binding due to localized
      structural changes in residues 3-10 and the exposed calcium ions. Our study
      suggests that the Gla 21 to Asp mutation disrupts function in the N-terminal
      region of the Gla domain without affecting structure in the C-terminal Gla domain
      region.

PMID- 8756688
TI  - Engineered disulfide bonds in staphylococcal nuclease: effects on the stability
      and conformation of the folded protein.
AB  - Efforts to enhance the stability of proteins by introducing engineered disulfide
      bonds have resulted in mixed success. Most approaches to the prediction of the
      energetic consequences of disulfide bond formation in proteins have considered
      only the destabilizing effects of cross-links on the unfolded state (chain
      entropy model) [Pace, C. N., Grimsley, G. R., Thomson, J. A., & Barnett, B. J.
      (1988) J. Biol. Chem. 263, 11820-11825: Doig, A. J., & Williams, D. H. (1991) J.
      Mol. Biol. 217, 389-398]. It seems clear, however, that disulfide bridges also
      can influence the stability of the native state. In order to assess the
      importance of the latter effect, we have studied four variants of staphylococcal
      nuclease (V8 strain) each containing one potential disulfide bridge created by
      changing two wild-type residues to cysteines by site-directed mutagenesis. In
      each case, one of the introduced cysteines was within the type VIa beta turn
      containing cis Pro117, and the other was located in the adjacent extended loop
      containing Gly79. In all four cases, the overall loop size was kept nearly
      constant (the number of residues in the loop between the two cysteines varied
      from 37 to 42) so as to minimize differences from chain entropy effects. The
      objective was to create variants in which a change in the reduction state of the
      disulfide would be coupled to a change in the position of the equilibrium between
      the cis and trans forms of the Xxx116-Pro117 peptide bond in the folded state of
      the protein. The position of this equilibrium, which can be detected by NMR
      spectroscopy, has been shown previously to correlate with the stability of the
      native protein. Its determination provides a measure of strain in the folded
      state. The thermal stabilities and free energies for unfolding by elevated
      temperature and guanidinium chloride were measured for each of the four mutants
      under conditions in which the introduced cysteines were cross-linked (oxidized)
      and unlinked (reduced). In addition, reduction potentials were determined for
      each mutant. Formation of the different disulfide bridges was found to induce
      varying levels of folded state strain. The stabilization energy of a given
      disulfide bridge could be predicted from the measured perturbation energy for the
      peptide bond isomerization, provided that energetic effects on the unfolded state
      were calculated according to the chain entropy model. Undiagnosed strain in
      native states of proteins may explain the variability observed in the
      stabilization provided by engineered disulfide bridges.

PMID- 8756689
TI  - Isolation and characterization of subunits of acetohydroxy acid synthase isozyme
      III and reconstitution of the holoenzyme.
AB  - The separately cloned large and small subunits of AHAS isozyme III from
      Escherichia coli have been isolated and purified. The essentially pure small
      subunit (17 kDa ilvH product) was obtained by a procedure exploiting its low
      solubility. The large, catalytic subunit (62 kDa ilvI product) was isolated by
      standard techniques, to > or = 95% purity. The large subunit has low catalytic
      activity relative to holoenzyme (approximately 5%) but shows similar substrate
      specificity and qualitatively similar cofactor dependence and inhibition by a
      sulfonylurea herbicide. Its activity is insensitive to valine, and the protein
      does not bind valine. The small subunit binds valine with Kd = 0.2 mM.
      Reconstitution of the holoenzyme from its subunits leads to a complex with the
      properties of the native protein, including valine inhibition of activity with Ki
      = 12 microM. Reconstitution titrations confirm the 1:1 stoichiometry of subunit
      assembly and a tendency to dissociation (about 50% dissociation near 0.1 microM
      subunit). Size exclusion HPLC indicates that either subunit alone is largely
      monomeric, and that assembly of the holoenzyme (two large + two small subunits,
      150-160 kDa) requires FAD. On the basis of its homology with pyruvate oxidase and
      pyruvate decarboxylase, we suggest that the active sites of AHAS III are located
      at the interface of a dimer of catalytic subunits. Our experiments suggest that
      such a dimer is not stable except in the presence of the small subunits. The
      association of valine with sites on the regulatory subunits presumably influences
      the active sites by an allosteric conformational effect.

PMID- 8756690
TI  - Folding properties of an annexin I domain: a 1H-15N NMR and CD study.
AB  - The annexin fold consists of four 70-residue domains with markedly homologous
      sequences and nearly identical structures. Each domain contains five helices
      designated A to E. Domain 2 of annexin I was obtained by chemical synthesis
      including ten specifically labeled residues and studied by 1H-15N NMR and
      circular dichroism (CD). In pure aqueous solution this annexin domain presents,
      at most, 25% of residual helix secondary structure compared to 75%-85% for the
      native helix content and thus does not constitute an autonomous folding unit.
      Dodecylphosphocholine (DPC) micelles were used to provide the annexin domain with
      non-specific hydrophobic interactions. The structuring effect of micelles was
      thoroughly investigated by CD and 1H-15N NMR. Most, but not all, of the native
      helix secondary structure was recovered at DPC saturation. NMR data made it
      possible to determine the intrinsic helix propensity hierarchy of the different
      helix segments of the domain: A approximately B approximately E > C, D. This
      hierarchy is remarkably well correlated with the location of the helices in the
      native protein since A, B, and E helices are those in contact with the remaining
      parts of the protein. This result tends to support the view that, for large
      proteins like annexins (35 kDa), high intrinsic secondary structure propensities,
      at least helix propensity, in selected protein segments is necessary for a
      correct folding process. As a consequence this also indicates that important
      information concerning the folding pathway is encoded in the protein sequence.

PMID- 8756691
TI  - Conformations of human apolipoprotein E(263-286) and E(267-289) in aqueous
      solutions of sodium dodecyl sulfate by CD and 1H NMR.
AB  - Structures of apoE(263-286) and apoE(267-289) have been determined in aqueous
      solution containing 90-fold molar excess of perdeuterated sodium dodecyl sulfate
      by CD and 1H NMR. Conformations were calculated by distance geometry based on 370
      and 276 NOE distance restraints, respectively. RMSD for superimposing the region
      265-284 from an ensemble of 41 structures for apoE(263-286) is 0.64 +/- 0.17 A
      for backbone atoms (N, C alpha, C = O) and 1.51 +/- 0.13 A for all atoms. The
      backbone RMSD for an ensemble of 37 structures for apoE(267-289) is 0.74 +/- 0.21
      A for the region 268-275 and 0.34 +/- 0.10 A for the region 276-286. A two-domain
      structure was found for apoE(267-289) with the C-terminal half adopting a very
      well defined helix and the N-terminal segment 268-275 a less well defined helix,
      suggesting that the N-terminus may weakly bind to SDS. For apoE(263-286), an
      amphipathic helix-bend-helix structural motif was found with all hydrophobic side
      chains on the concave face. The existence of a bend around residues Q273 to G278
      is consistent with their temperature coefficients of amide protons as well as
      secondary shifts of alpha-protons. Comparison of the structures of the two
      peptides revealed that the enhanced binding of apoE(263-286) to lipid could be
      attributed to the formation of a hydrophobic cluster consisting of residues W264,
      F265, L268, and V269. Aromatic side chains are proposed to be especially
      important in anchoring apolipoprotein fragments to micelles.

PMID- 8756692
TI  - Proteolytic cleavage sites of native AE2 anion exchanger in gastric mucosal
      membranes.
AB  - The AE2 anion exchanger in pig and rabbit gastric mucosal membranes was subjected
      to limited proteolysis with trypsin, chymotrypsin, and papain, and to enzymatic N
      deglycosylation. A monoclonal antibody to the AE2 C-terminal peptide was raised,
      characterized, and used to purify pig AE2 and its C-terminal cleavage products.
      Five distinct proteolytic cleavage sites within the AE2 transmembrane domain were
      defined by amino acid sequencing. The amino acid sequence of pig AE2 in the
      region encompassing the N-glycosylated Z-loop was also determined by RT-PCR.
      Tryptic cleavage of pig AE2 in the Z-loop produced C-terminal glycopeptides and
      was unaffected by deglycosylation, whereas the smaller rabbit AE2 C-terminal
      tryptic peptide lacked oligosaccharide, consistent with the respective amino acid
      sequences. The third consensus N-glycosylation site in pig Z-loop was
      heterogeneously glycosylated. Rapid papain cleavage in the Z-loop and slower
      cleavage in loop 7-8 produced C-terminal peptide products which were not N
      glycosylated. Chymotryptic cleavage of the rabbit AE2 Z-loop required prior
      deglycosylation. Chymotryptic cleavage in the pig AE2 Z-loop produced C-terminal
      glycopeptides. Prior deglycosylation of pig AE2 unmasked novel, ionic strength
      sensitive chymotryptic cleavage sites in the adjacent exofacial loop 7-8. These
      results provide experimental confirmation for some aspects of AE2 topography
      previously predicted from primary structure alone.

PMID- 8756693
TI  - Replacement of the conserved tyrosine 1210 by phenylalanine in the insulin
      receptor affects insulin-induced dephosphorylation of focal adhesion kinase but
      leaves other responses intact.
AB  - The families of tyrosine and serine/threonine kinases exhibit shared clusters of
      conserved amino acid residues. Some conserved residues are confined to the family
      of tyrosine kinases (TKs), like Tyr at position 1210 in the insulin receptor.
      Nearly all TKs have at this position Tyr, whereas Ser/Thr kinases generally have
      Phe at this site. The three-dimensional structure of the insulin receptor TK
      domain shows Tyr1210 to be located in the cleft, below bound ATP, in a region
      which potentially contributes to substrate binding. We have examined whether this
      specific Tyr residue contributes to the generation of TK-specific responses, such
      as Tyr phosphorylation of Shc, activation of Ras and Erk1,2, and stimulation of
      DNA synthesis. In addition, we have examined the contribution of Tyr1210 to
      insulin receptor-specific responses as Tyr phosphorylation of IRS1, stimulation
      of glycogen synthesis, and dephosphorylation of focal adhesion kinase (FAK). Wild
      type and a mutant insulin receptor, in which Tyr1210 was replaced by Phe, were
      stably expressed in CHO cells, and clones expressing similar numbers of insulin
      receptors were selected. It was found that replacement of Tyr1210 by Phe resulted
      in a receptor which was nearly inactive in inducing dephosphorylation of FAK. The
      mutant receptor was able to induce RasGTP formation, glycogen synthesis, and
      activation of phosphatidylinositol 3-kinase, though the magnitude of stimulation
      of some responses was decreased. These findings indicate that Tyr1210 is not
      essential for the induction of tyrosine kinase-specific responses, such as
      activation of the Shc/Ras/Erk1,2 pathway and mitogenicity. On the other hand, the
      abrogation of insulin-induced FAK dephosphorylation indicates that Tyr1210 is
      involved in coupling of the activated receptor to some downstream targets. Thus,
      Tyr1210 may fine tune the signal generated by the activated insulin receptor.

PMID- 8756694
TI  - Accessibility and environment probing using cysteine residues introduced along
      the putative transmembrane domain of the major coat protein of bacteriophage M13.
AB  - The major coat protein of the filamentous bacteriophage M13 is located in the
      inner membrane of host cell Escherichia coli prior to assembly into virions. To
      identify the transmembrane domain of the coat protein, we have introduced unique
      cysteine residues along the putative transmembrane domain at position 25, 31, 33,
      36, 38, 46, 47, 49, or 50. The mutant major coat protein was solubilized by
      membrane-mimicking detergents or reconstituted into mixed bilayers of
      phospholipids. Information about the environmental polarity was deduced from the
      wavelength of maximum emission, using N-[[(iodoacetyl)-amino)ethyl]-1
      sulfonaphthylamine (IAEDANS) attached to the SH groups of the cysteines as a
      fluorescent probe. Additional information was obtained by determining the
      accessibility of AEDANS for the fluorescence quencher molecules acrylamide and 5
      doxylstearic acid, and the reactivity of the cysteine's sulfhydryl group toward
      5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). Our data suggest transmembrane
      boundaries close to residue 25 and 46, with residue 25 inside the hydrophobic
      part of the membrane in very close proximity to the membrane-water interface and
      residue 46 located at the membrane-water interface. Domains of the mutant coat
      protein which are packed or coated by cholate molecules and various other
      detergents [except for sodium dodecyl sulfate (SDS)] are at least similarly
      packed by phospholipid molecules in bilayers. SDS is a good solubilizing
      detergent but badly mimics the typical nature of a membrane structure. The
      overall results are interpreted with respect to the established conformation of
      the coat protein and its membrane anchoring mechanism.

PMID- 8756696
TI  - Orientation of tryptophan-26 in coat protein subunits of the filamentous virus Ff
      by polarized Raman microspectroscopy.
AB  - The Ff filamentous virus, which includes the closely related strains fd, fl and
      M13, serves as a model for membrane protein assembly and is employed extensively
      as a cloning vector and vehicle for peptide display. The threadlike virion
      (approximately 6 x 880 nm) comprises a single-stranded DNA genome sheathed by
      approximately 2700 copies of a 50-residue alpha-helical subunit, the product of
      viral gene VIII. The pVIII subunit contains a single tryptophan residue
      (tryptophan-26) which is essential for assembly. We have employed polarized Raman
      microspectroscopy to determine the orientation of tryptophan-26 in pVIII subunits
      of oriented fd fibers. The present application is based upon the transfer of
      tryptophan Raman tensors from a recent study of N-acetyl-L-tryptophan single
      crystals [Tsuboi et al. (1996) J. Mol. Struct. 379, 43-50]. The polarized Raman
      spectra of fd indicate that the plane of the indole ring in each pVIII subunit is
      close to parallel to the virion axis. In this orientation, the line connecting
      indole ring atoms N1 and C2 is nearly perpendicular to the virion axis, while the
      indole pseudo-2-fold axis (a line connecting atom C2 to the midpoint of the C5-C6
      bond) is approximately 36 degrees from the virion axis. We have used the present
      results in combination with preferred tryptophan side-chain torsions [chi 1 (C3-C
      beta-C alpha-N) and chi 2.1 (C2-C3-C beta-C alpha)] in other proteins and a
      previously determined experimental value of chi 2.1 in fd [Aubrey. K. L., &
      Thomas, G. J., Jr. (1991) Biophys, J. 60, 1337-1349] to propose a detailed
      molecular model for the orientation of the tryptophan-26 side chain in the native
      virus.

PMID- 8756695
TI  - Specific phosphorylation of a site in the full-length form of the alpha 1 subunit
      of the cardiac L-type calcium channel by adenosine 3',5'-cyclic monophosphate
      dependent protein kinase.
AB  - Voltage-gated L-type Ca2+ channels mediate Ca2+ entry into cells in response to
      membrane depolarization. Ca2+ entry through the cardiac Ca2+ channel determines
      the rate and force of contraction, and modulation of Ca2+ channel activity by
      beta-adrenergic agents acting through adenosine 3',5'-cyclic monophosphate-(cAMP)
      dependent protein phosphorylation contributes to physiological regulation of
      cardiac function by the sympathetic nervous system. Immunoblotting experiments
      using site-directed anti-peptide antibodies against different peptide segments
      indicate that the alpha 1 subunit of the cardiac L-type Ca2+ channel exists in
      two size forms with apparent molecular masses of 240 and 210 kDa, which we call
      alpha 1(242) and alpha 1(210), Alpha 1(242) corresponds to the full-length
      cardiac alpha 1 subunit predicted from its cDNA sequence, while alpha 1(210) is
      truncated at its COOH terminus. Only alpha 1(242) is phosphorylated in vitro by
      cAMP-dependent protein kinase. Protein microsequencing and peptide mapping of
      wild-type and mutant fusion proteins show that this phosphorylation occurs at
      serine 1928 near the COOH terminus. Phosphorylation of this residue can be
      detected by phosphospecific antibodies raised against the corresponding
      phosphopeptide. Experiments with these antibodies show that alpha 1(242) is
      phosphorylated in intact cells expressing the cardiac alpha 1 subunit in response
      to increased intracellular levels of cAMP. These results identify serine 1928 on
      the alpha 1 subunit as a possible site of regulation by cAMP-dependent
      phosphorylation.

PMID- 8756697
TI  - Human erythrocyte sugar transport is incompatible with available carrier models.
AB  - GLUT1-mediated, passive D-glucose transport in human erythrocytes is asymmetric,
      Vmax and K(m)(app) for D-glucose uptake at 4 degrees C are 10-fold lower than
      Vmax and K(m)(app) for D-glucose export. Transport asymmetry is not observed for
      GLUT1-mediated 3-O-methylglucose transport in rat, rabbit, and avian erythrocytes
      and rat adipocytes where Vmax for sugar uptake and exit are identical. This
      suggests that transport asymmetry is either an intrinsic catalytic property of
      human GLUT1 or that factors present in human erythrocytes affect GLUT1-mediated
      sugar transport. In the present study we assess human erythrocyte sugar transport
      asymmetry by direct measurement of sugar transport rates and by analysis of the
      effects of intra- and extracellular sugars on cytochalasin B binding to the sugar
      export site. We also perform internal consistency tests to determine whether the
      measured, steady-state 3-O-methylglucose transport properties of human
      erythrocytes agree with those expected of two hypothetical models for protein
      mediated sugar transport. The simple-carrier hypothesis describes a transporter
      that alternately exposes sugar import and sugar export pathways. The fixed-site
      carrier hypothesis describes a sugar transporter that simultaneously exposes
      sugar import and sugar export pathways. Steady-state 3-O-methylglucose transport
      in human erythrocytes at 4 degrees C is asymmetric. Vmax and K(m)(app) for sugar
      uptake are 10-fold lower than Vmax and K(m)(app) for sugar export. Phloretin
      inhibitable cytochalasin B binding to intact red cells is unaffected by
      extracellular D-glucose but is competitively inhibited by intracellular D
      glucose. This inhibition is reduced by 13% +/- 4% when saturating extracellular D
      glucose levels are also present. Assuming transport is mediated by a simple
      carrier and that cytochalasin B and intracellular D-glucose binding sites are
      mutually exclusive, the cytochalasin B binding data are explained only if
      transport is almost symmetric (Vmax exit = 1.4 Vmax entry). The cytochalasin B
      binding data are consistent with both symmetric and asymmetric fixed-site
      carriers. Analysis of 3-O-methylglucose, 2-deoxy-D-glucose, and D-glucose uptake
      in the presence of intracellular 3-O-methylglucose, demonstrates significant
      divergence in experimental and theoretical transport behaviors. We conclude
      either that human erythrocyte sugar transport is mediated by a carrier mechanism
      that is fundamentally different from those considered previously or that human
      erythrocyte-specific factors prevent accurate determination of GLUT1-mediated
      sugar translocation across the cell membrane. We suggest that GLUT1-mediated
      sugar transport in all cells is an intrinsically symmetric process but that
      intracellular sugar complexation in human red cells prevents accurate
      determination of transport rates.

PMID- 8756698
TI  - Cofactor A is a molecular chaperone required for beta-tubulin folding: functional
      and structural characterization.
AB  - Actin and tubulin polypeptide chains acquire their native conformation in the
      presence of the chaperonin containing TCP-1 (CCT) and, in the case of alpha- and
      beta-tubulin additional protein cofactors. We recently identified one of these
      cofactors, termed cofactor A, that is required for the proper folding of the beta
      tubulin chain [Gao et al. (1994) J. Cell. Biol. 125, 989-996]. We show here that
      cofactor A, a monomeric protein that has no measurable affinity for nucleotides,
      is a highly conserved protein among vertebrates. Its NH2-terminal region is
      essential for the structural integrity of the protein and consequently for its
      activity. We demonstrate that cofactor A does not interact with CCT nor does it
      affect the intrinsic ATPase activity of CCT, alone or in the presence of
      different target proteins. Thus, unlike GroES, cofactor A does not modulate or
      coordinate ATP hydrolysis. It does not act as a nucleotide exchange factor or a
      catalyst in tubulin folding. Rather, we demonstrate that cofactor A participates
      in the tubulin folding process by interacting with a folding intermediate of beta
      tubulin that is released from CCT. Our data imply that cofactor A is a chaperone
      involved in tubulin folding.

PMID- 8756699
TI  - Identification of an epitope in antithrombin appearing on insertion of the
      reactive-bond loop into the A beta-sheet.
AB  - Previous work has shown that insertion of the reactive-bond loop of antithrombin
      into the main beta-sheet of the inhibitor, the A sheet, leads to exposure of
      epitopes that are not present in intact antithrombin. Identical epitopes are
      exposed in antithrombin-proteinase complexes, inferring that the reactive-bond
      loop is inserted into the A beta-sheet also in these complexes. Loop insertion
      thus presumably is involved in the mechanism of inhibition of target proteinases.
      In this work, we have identified a linear epitope in bovine antithrombin that
      reacts with antibodies specific for loop-inserted forms of the inhibitor. This
      epitope is a hexapeptide sequence comprising residues 342-347, Glu-Asp-Leu-Phe
      Ser-Pro, and is located on the surface of the protein just carboxy-terminal of
      helix I. The Phe residue of this epitope is highly conserved in members of the
      serpin superfamily and appears to stabilize the region of the epitope in
      antithrombin and other serpins by interacting with the protein core. The
      conformational change involving expansion of the A beta-sheet following insertion
      of the reactive-bond loop is presumably transmitted through this Phe residue to
      the epitope region, thereby rendering this region accessible to antibodies.

PMID- 8756700
TI  - Identification from a phage display library of peptides that bind to toxic shock
      syndrome toxin-1 and that inhibit its binding to major histocompatibility complex
      (MHC) class II molecules.
AB  - Phage display technique is a powerful tool with which to identify novel binding
      sequences for antibody and receptor targets. Few studies, however, have used this
      technology to select affinity peptides for ligand molecules. Here, we screened a
      peptide phage library for binding to toxic shock syndrome toxin 1 (TSST-1) to
      examine whether peptide ligands for TSST-1 which mimic the structure of major
      histocompatibility complex (MHC) class II receptors could be identified. After
      three cycles of biopanning, four potent sequences reactive with TSST-1 were
      isolated (designated phages 2, 3, 8, and 11). Selected phage were found to react
      specifically with TSST-1 but not with other staphylococcal exotoxins. A synthetic
      peptide (pep3) corresponding to the most frequently identified sequence (phage3)
      was shown to inhibit binding of all four isolated phage to TSST-1, suggesting
      that they bind to a common site on TSST-1. Furthermore, pep3 was shown to compete
      with MHC class II molecules for binding to TSST-1 in a concentration-dependent
      manner. Comparison of their sequences with MHC class II molecules revealed that
      phage8 shared sequence homology with two regions of the beta chain of MHC class
      II molecules: amino acids 57-62, containing a residue (Tyr-60) involved in TSST-1
      binding as suggested by X-ray crystallographic data of TSST-1-MHC class II
      complex; and amino acids 188-193, a region not previously known as a contact
      domain. These results suggest that the selected sequences recognized the MHC
      class II binding site on TSST-1. Thus, affinity selection for peptides binding to
      ligand molecules (e.g., TSST-1) rather than their cognate receptors (e.g., MHC
      class II) from a random phage display library represents a useful approach to
      understanding receptor-ligand interactions.

PMID- 8756701
TI  - Plasma factor XIII binds specifically to fibrinogen molecules containing gamma
      chains.
AB  - The difference between peak 1 and peak 2 fibrinogen lies in their gamma chains.
      Peak 1 molecules contain 2 gamma A chains; peak 2 molecules contain 1 gamma A and
      1 gamma chain, the latter of which contains a 20 amino acid extension (gamma 408
      427) replacing the carboxyl-terminal 4 amino acids of the gamma A chain (gamma A
      408-411). While the existence of gamma chains in plasma fibrinogen molecules has
      been known for many years, their function remains unknown. When fibrinogen is
      purified from plasma, the factor XIII zymogen (A2B2) copurifies with it and is
      found only in the peak 2 fibrinogen when this fraction is separated from peak 1
      fibrinogen by ion-exchange chromatography on DEAE-cellulose. Factor XIII alone
      applied to the same DEAE column elutes at a position between peak 1 and peak 2.
      When mixtures of peak 1 fibrinogen plus factor XIII or peak 2 fibrinogen plus
      factor XIII are applied to DEAE columns, the peak 1/factor XIII mixture elutes in
      two peaks, whereas the peak 2/factor XIII mixture elutes in the peak 2 fibrinogen
      position. Gel sieving on Superose 6 of peak 1/factor XIII mixtures results in two
      protein peaks, the first of which contains the fibrinogen. Most factor XIII
      activity elutes in the second peak with a small amount of activity emerging with
      the trailing end of the fibrinogen peak. Gel sieving of mixtures of peak 2 and
      factor XIII results in a single protein peak with all factor XIII activity
      emerging with the leading edge of the fibrinogen peak. The interaction between
      peak 2 fibrinogen and plasma factor XIII appears to be through binding to the B
      subunit of factor XIII since placental or platelet factor XIII (A2), which does
      not contain B subunits, elutes independently from peak 2 fibrinogen on DEAE
      cellulose chromatography. The results indicate that peak 2 fibrinogen gamma
      chains have a physiologically significant affinity for the B subunits of plasma
      factor XIII and that through this interaction fibrinogen serves as a carrier for
      the plasma zymogen in circulating blood.

PMID- 8756702
TI  - Yeast geranylgeranyltransferase type-II: steady state kinetic studies of the
      recombinant enzyme.
AB  - Rab proteins in mammalian cells, or Ypt1p and Sec4p in yeast, regulate vesicular
      traffic. Prenylation of these small GTP-binding proteins is required for membrane
      attachment and subsequent biological activity. Yeast protein
      geranylgeranyltransferase type-II (PGGTase-II) catalyzes the prenylation of Ypt1p
      in the presence of an escort protein, Msi4p. The genes encoding the alpha-(BET4)
      and beta-(BET2) subunits of PGGTase-II were translationally coupled by
      overlapping the BET4-BET2 stop/start codons and by adding a ribosome-binding site
      near the 3'-end of BET4 that fused an -EEF C-terminal alpha-tubulin epitope to
      Bet4p. Active recombinant heterodimer was purified by chromatography on DE52 and
      anti-alpha-tubulin columns. Recombinant Msi4p with an N-terminal polyhistidine
      leader was purified on a Ni(2+)-Sepharose column, followed by gel filtration and
      ion exchange chromatography. An escort protein, Msi4p, was necessary for
      geranylgeranylation of Ypt1p by yeast PGGTase-II. Michaelis constants for GGPP
      and Ypt1p were 1.6 and 1.1 microM, respectively; Vmax = 1.7 nmol min-1 mg-1 for
      yeast PGGTase-II. Typical Michaelis-Menten behavior was also seen for the enzyme
      for varied concentrations of Msi4p, with a maximal catalytic activity seen for a
      10-fold excess of escort protein over enzyme. In contrast to previous reports,
      PGGTase-II requires both Zn2+ and Mg2+ for maximal activity, although Zn2+
      becomes inhibitory at concentrations above approximately 10 microM. Prenylated
      Ypt1p obtained after incubation of Ypt1p with PGGTase-II, Msi4p, and
      geranylgeranyl diphosphate was digested with trypsin. The C-terminal peptide
      fragment from modified Ypt1p was purified by HPLC and analyzed by electrospray
      mass spectrometry. The mass of the fragment is consistent with the 12-mer C
      terminal amino acid fragment predicted from proteolysis by trypsin with both
      cysteine residues modified by geranylgeranyl moieties.

PMID- 8756704
TI  - Biophysical characterization of wild-type and mutant bacteriophage IKe major coat
      protein in the virion and in detergent micelles.
AB  - Interactions between the filamentous bacteriophage major coat protein and its
      environment differ markedly between the membrane-bound assembly intermediate
      which spans the lipid bilayer and the phage coat protein which makes up the
      capsid of the virion. Nonetheless, both reflect successful strategies to
      sequester the hydrophobic regions of the coat protein away from the aqueous
      milieu. To characterize the roles of individual residues in the conformation,
      stability, and oligomerization of the coat protein in both the virion and in
      detergent micelles, wild-type IKe and M13 coat proteins, together with a library
      of over 40 IKe coat protein mutants, were studied using circular dichroism (CD),
      fluorescence, and solution nuclear magnetic resonance (NMR) spectroscopies. The
      largely helical conformations of coat protein in IKe wild-type and mutant virions
      were found to be very similar by CD, demonstrating that the overall organization
      of the phage can accommodate a diverse range of amino acid substitutions in the
      major coat protein. Intrinsic Trp fluorescence showed that the polarity of the
      Trp 29 environment in the virion was modulated by residues within one helical
      turn of this locus. Characterization of IKe phage growth and plaquing properties
      highlighted the importance of Pro 30 in maintaining viability. As well, the Pro
      30 mutants were the only substitutions which rendered the detergent-solubilized
      coat protein less thermostable and additionally altered the polarity of the Trp
      29 environment. The Pro 30 Gly mutant exhibited numerous 1H and 15N chemical
      shift changes between residues Ile 25 and Ala 38 in the 2D 1H-15N HSQC spectrum
      in myristoyllysophosphatidylglycerol (MPG) micelles, demonstrating that the
      effect of the substitution is propagated beyond adjacent residues. The overall
      results highlight the stabilizing effect of Pro in the first turn of a
      transmembrane helix and the importance of hydrophobicity in modulating the
      oligomerization and stability of coat protein both in the phage and in detergent
      micelles.

PMID- 8756703
TI  - Gain of D-alanyl-D-lactate or D-lactyl-D-alanine synthetase activities in three
      active-site mutants of the Escherichia coli D-alanyl-D-alanine ligase B.
AB  - Escherichia coli D-Ala-D-Ala ligase (Ddl) and the vancomycin resistance
      conferring protein VanA are homologues, but VanA has gained the ability to
      activate D-lactate (D-Lac) and make the depsipeptide D-Ala-D-Lac as well as D-Ala
      D-Ala. This depsipeptide ligase activity of VanA is its crucial catalytic
      function necessary for phenotypic vancomycin resistance. We report here that
      three E. coli DdlB active-site mutants that we made previously based on X-ray
      structure/function predictions have gained interesting new ligase activities.
      Y216, S150, and E15 form a hydrogen-bonding triad that orients an omega-loop to
      close over the active site and also to orient substrate D-Ala1. Mutants Y216F and
      S150A have gained depsipeptide (D-Ala-D-Lac, D-Ala-D-hydroxybutyrate) ligase
      activity with dipeptide/depsipeptide partition ratios that mimic the pH behavior
      of VanA. E15Q has negligible depsipeptide synthetase activity but now uniquely
      activates D-Lac as the electrophilic rather than the nucleophilic partner for
      condensation with D-Ala to make a regioisomeric D-Lac-D-Ala, an amide rather than
      an ester product. These results provide insights into the active-site
      architecture of the ligases and the subsites for recognition of D-Ala VS D-Lac
      and predict the Y216F substitution will impart D-Ala-D-Lac synthetase activity to
      Ddls from Grampositive bacteria with intrinsic resistance to vancomycin.

PMID- 8756705
TI  - Sequence and environmental effects on the self-assembly of DNA oligomers
      possessing GxT2Gy segments.
AB  - It is well-known that DNA oligomers possessing contiguous guanine bases can
      assume non-Watson-Crick type structures through the formation of four-stranded
      species. The architecture of these four-stranded structures is highly dependent
      upon the sequence of the DNA and the conditions (e.g., buffer, pH, ionic
      strength, cations present, and temperature) under which the DNA is prepared. This
      lab has previously reported the self-assembly of DNA oligomers of sequence
      C4T4G4T1-4G4 into multistranded high molecular weight species [Dai, T.-Y.,
      Marotta, S. P., & Sheardy, R. D. (1995) Biochemistry 34, 3655-3662]. In order to
      further investigate the sequence and environmental effects on the self-assembly
      of DNA oligomers possessing GxT2Gy (where x = 1, 3, or 4 and y = 2-5) segments,
      the synthesis of a number of such oligomers was undertaken. DNA samples were
      prepared in standard phosphate buffer (10 mM phosphate, pH 7.0) and NaCl, KCl
      and/or MgCl2 added to different concentrations in order to evaluate the influence
      of the cations and their concentrations on the self-assembly of the DNA
      oligomers. The self-assembly of these oligomers was monitored by nondenaturing
      polyacrylamide gel electrophoresis and circular dichroism studies.
      Electrophoresis of the oligomers in either 100 mM K+ or 50 mM Na+ with 50 mM K+
      indicated the formation of one or two molecular species for these oligomers. In
      contrast, electrophoresis of these oligomers in the presence of both 100 mM K+
      and 20 mM Mg2+ give a ladder of multiple bands of high molecular weight
      indicative of multistanded DNA structure formation. The results presented here
      indicate that self-assembly into high molecular weight species is favored by the
      presence of Mg2+ as well as the presence of four or more bases in the terminal Gy
      segment. These results also suggest that the structure of telomeric DNA, which
      possesses similar sequences, may be quite unusual.

PMID- 8756706
TI  - Magnesium ions are required by Bacillus subtilis ribonuclease P RNA for both
      binding and cleaving precursor tRNAAsp.
AB  - The multiple roles Mg2+ plays in ribozyme-catalyzed reactions in stabilizing RNA
      structure, enhancing the affinity of bound substrates, and increasing catalysis
      are delineated for the RNA component of ribonuclease P (RNase P RNA) by a
      combination of steady-state kinetics, transient kinetics, and equilibrium binding
      measurements. Divalent metal ions cooperatively increase the affinity of Bacillus
      subtilis RNase P RNA for B. subtilis tRNA(Asp) more than 10(3)-fold, consistent
      with at least two additional magnesium ions binding to the RNase P RNA.tRNA
      complex. Monovalent cations also decrease KD(tRNA) and reduce, but do not
      eliminate, the dependence on magnesium ions, demonstrating that nonspecific
      electrostatic shielding is not sufficient to explain the requirement for high
      salt. Both di- and monovalent cations promote the high affinity of tRNA by
      forming contacts in the binary complex that reduce the dissociation rate constant
      for tRNA. Additionally, the hyperbolic dependence of the hydrolytic rate constant
      on the concentration of magnesium with a K1/2 approximately equal to 36 mM
      suggests that a third low-affinity divalent metal ion stabilizes the transition
      state for pre-tRNA cleavage. Furthermore, many (about 100) magnesium ions bind
      independently to RNase P RNA with higher affinity than the K1/2 of any of the
      functionally characterized magnesium binding sites. Therefore, the magnesium
      binding sites that have differential affinity in either the "folded" species or
      binary complex are a small subset of the total number of associated magnesium
      ions. In summary, the importance of magnesium bound to RNase P RNA can be
      separated functionally into three crucial roles: at least three sites stabilize
      the folded RNA tertiary structure [Pan. T. (1995) Biochemistry 34, 902-909], at
      least two sites enhance the formation of complexes of RNase P RNA with pre-tRNA
      or tRNA, and at least one site stabilizes the transition state for pre-tRNA
      cleavage.

PMID- 8756707
TI  - Thermodynamic characterization of interactions of native bovine serum albumin
      with highly excluded (glycine betaine) and moderately accumulated (urea) solutes
      by a novel application of vapor pressure osmometry.
AB  - The thermodynamic consequences of interactions of native bovine serum albumin
      (BSA) with two smaller solutes (glycine betaine or urea) in aqueous solution are
      characterized by a novel application of vapor pressure osmometry (VPO), which
      demonstrates the utility of this method of investigating preferential
      interactions involving solutes that are either accumulated or excluded near the
      surface of a protein. From VPO measurements of osmolality (water activity) as a
      function of the solute concentration in the presence and absence of BSA, we
      determine the dependence of the solute molarity (C3) on that of BSA (C2) at fixed
      temperature (37 degrees C), pressure (approximately 1 atm), and osmolality (over
      the range 0-1.6 molal). After some thermodynamic transformations, these results
      yield values of [formula: see text] which characterizes the interdependence of
      solute molalities when temperature, pressure, and the chemical potential of
      solute 3 are fixed. This form of the preferential interaction coefficient can be
      interpreted directly in terms of the molecular exclusion or accumulation of the
      solute (relative to water) near the protein surface. Within experimental
      uncertainty, [formula: see text] is proportional to m3 both for glycine betaine
      (0-0.9 m) and for urea (0-1.6 m). For glycine betaine [formula: see text] = -49
      +/- 4, a value consistent with the interpretation that this solute is completely
      excluded from the hydrated surface of BSA, whereas for urea [formula: see text] =
      6 +/- 1, which indicates a moderate extent of accumulation at the surface of
      native BSA. The preferential accumulation of solutes (e.g., urea) that have some
      binding affinity for a protein can be quantified and interpreted using the two
      domain model if the extent of hydration of the protein has been determined using
      a completely excluded solute (e.g., glycine betaine). Complete exclusion from the
      local hydration domain surrounding proteins, if general, justifies the use of
      glycine betaine as a thermodynamic probe of the changes in hydration that
      accompany protein folding, protein association, and protein-ligand binding
      interactions.

PMID- 8756708
TI  - Identifying and characterizing a structural domain of protein disulfide
      isomerase.
AB  - Protein disulfide isomerase (PDI) appears on the basis of its primary structure
      to be a multidomain protein, but the number and nature of the domains has been
      uncertain. Two of the domains, a and a', which are homologous to thioredoxin and
      active in catalysis of disulfide bond formation, have been identified and
      characterized previously. Sections of the N-terminal half of the PDI sequence
      have been expressed and the limits of their folded structures delineated by
      limited proteolysis. In addition to the a-domain, the boundaries of a domain with
      no activity on thiol/disulfide groups, designated b, have been identified. This
      domain has been produced independently; its cooperative unfolding transition and
      its CD and NMR spectra confirm that it is an autonomously folded structure in
      isolation and when part of PDI. Fusion of the b-domain to the a-domain, as occurs
      naturally in the first half of PDI, did not alter substantially the catalytic
      activity of the a-domain. It still catalyzes only a subset of the thiol/disulfide
      exchange reactions of intact PDI and has a reduced ability to catalyze protein
      disulfide rearrangements. The a- and b-domains account structurally for virtually
      all of the first half of the PDI polypeptide chain, and it is very unlikely that
      there exists a proposed third domain homologous to the estrogen receptor. The b
      domain exhibits some sequence homology to calsequestrin, a calcium binding
      protein from the sarcoplasmic reticulum of muscle.

PMID- 8756709
TI  - Hydrogen-bond interactions of the primary donor of the photosynthetic purple
      sulfur bacterium Chromatium tepidum.
AB  - We have used near-infrared Fourier transform (pre)resonance Raman spectroscopy to
      determine the protein interactions with the bacteriochlorophyll (BChl) dimer
      constituting the primary electron donor, P, in the reaction center (RC) from the
      thermophilic purple sulfur bacterium Chromatium tepidum. In addition, we report
      the alignment of partial sequences of the L and M protein subunits of C. tepidum
      RCs in the vicinity of the primary donor with those of Rhodobacter sphaeroides
      and Rhodopseudomonas viridis. Taken together, these results enable us to propose
      the hydrogen-bonding pattern and the H-bond donors to the conjugated carbonyl
      groups of P. Selective excitation (1064-nm laser radiation) of the FT (pre)
      resonance Raman spectra of P in its neutral (P degree) and oxidized (P degree +)
      states were obtained via their electronic absorption bands at 876 and 1240 nm,
      respectively. The P degree spectrum exhibits vibrational frequencies at 1608,
      1616, 1633, and 1697 cm-1 which bleach upon P oxidation. The P degree + spectrum
      exhibits new bands at 1600, 1639, and 1719 cm-1. The 1608-cm-1 band, which
      downshifts to 1600 cm-1 upon oxidation, is assigned to a CaCm methine bridge
      stretching mode of the P dimer, indicating that each BChl molecule possesses a
      single axial ligand (His L181 and His M201, from the sequence alignment). The
      1616- and 1633-cm-1 bands correspond to two H-bonded pi-conjugated acetyl
      carbonyl groups of each BChl molecule. with different H-bond strengths: the 1616
      cm-1 band is assigned to the PL C2 acetyl group which is H-bonded to a histidine
      residue (His L176), while the 1633-cm-1 band is assigned to the PM C2 acetyl
      carbonyl, H-bonded to a tyrosine residue (Tyr M196). Both PL and PM C9 keto
      carbonyls are free from interactions and vibrate at the same frequency (1697 cm
      1). Thus, the H-bond pattern of the primary donor of C. tepidum differs from that
      of Rb. sphaeroides in the extra H-bond to the PM C2 acetyl carbonyl group; that
      of PL is H-bonded to a histidine residue in both primary donors (His L168 in Rb.
      sphaeroides and His L176 in C. tepidum). The P degree/P degree + redox midpoint
      potentials were measured to be +497 and +526 mV for isolated C. tepidum RCs with
      and without the associated tetraheme cytochrome c subunit, respectively, and +502
      mV for intracytoplasmic membranes. The positive charge localization was estimated
      to be 69% in favor of PL, indicating a more delocalized situation over the
      primary donor of C. tepidum than that of Rb. sphaeroides (estimated to be 80% on
      PL). These differences in physicochemical properties are discussed with respect
      to the proposed structural model for the microenvironment of the primary donor of
      C. tepidum.

PMID- 8756710
TI  - Specific inhibition of in vitro transcription elongation by triplex-forming
      oligonucleotide-intercalator conjugates targeted to HIV proviral DNA.
AB  - A 16-base pair oligo(purine)-oligo(pyrimidine) sequence present in the coding
      region of two HIV 1 proviral genes (pol and nef) was chosen as a target for
      triplex-forming oligonucleotides in in vitro transcription assays. Inhibition of
      transcription elongation was observed with triplex-forming oligonucleotide
      acridine conjugates (Acr-15-TCG:5'-Acr-T4CT4G6-3' and Acr-9-TC:5'-Acr-T4CT4-3'
      where C is 5-methylcytosine) under conditions where the unsubstituted oligomers
      did not exhibit any inhibitory effect. Both SP6 bacteriophage RNA polymerase and
      eukaryotic RNA polymerase II were physically blocked by such a triplex barrier.
      The polymerase arrest is caused by the triple-helical complex involving the
      hydrogen-bonded oligonucleotide stabilized by the intercalated moiety and not
      solely by the acridine molecule specifically intercalated at the duplex-triplex
      junction. The stability of the triple-helical complex formed by the 15-mer
      containing thymines, cytosine, and guanines (15-TCG) and involving the formation
      of six contiguous C.GxG base triplets was strongly enhanced in the presence of a
      benzopyridoindole derivative (BePI), which intercalates in triplex structures.
      This improvement of the binding affinity led to an increased inhibition of
      transcription elongation. The present results demonstrate the necessity to use
      triplex-forming oligonucleotides with high binding affinity and a long residence
      time on their double-stranded target to efficiently inhibit transcription
      elongation. These data provide a rational basis for the optimization and the
      development of triplex-forming oligonucleotides as transcriptional blockers, even
      when they are targeted to the transcribed portion of a gene, downstream of the
      transcription initiation site.

PMID- 8756711
TI  - Molecular analysis of the second template switch during reverse transcription of
      the HIV RNA template.
AB  - The molecular events leading to the second template switch during reverse
      transcription of the HIV genome were studied in a defined in-vitro system. In
      order to investigate displacement of the tRNA(lys) primer from the primer binding
      site (PBS) of the viral genomic RNA, following DNA synthesis, we produced an HIV
      RNA/DNA substrate that resembles the intermediate reverse transcription complex
      formed prior to the second template switch. Partial tRNA(lys) primer displacement
      was observed during plus (+) strand DNA synthesis and during minus (-) strand DNA
      elongation. We found two determinants that may serve as a stop signal for (+) DNA
      strong stop synthesis, the A(m) at position 19 of the natural tRNA(lys) and the
      secondary structure at the PBS sequence. The later signal appears to constitute a
      stronger terminator in-vitro. The 3' end of the nascent (-) DNA strand prior to
      the second template switch was also determined. It was mapped to the U5-PBS
      junction at the site for the first endonucleolytic cut introduced by the RNase H
      activity of the HIV reverse transcriptase (RT). Thus, different signals dictate
      the arrest of (-) and (+) nascent DNA synthesis. These stop signals appear to be
      required for the subsequent second template switch. However, an excess of (-) DNA
      "acceptor" molecules, having a 18-base sequence complementary to the (+) DNA
      "donor" template, was required to demonstrate the actual template switch in the
      in-vitro system. Taken together these results indicate that the reverse
      transcriptase can catalyze all the steps leading to the second template switch
      and auxiliary viral proteins may act to enhance the efficiency of this step
      during the reverse transcription process.

PMID- 8756712
TI  - Functional domains of the 70-kilodalton subunit of human replication protein A.
AB  - Human replication protein A (RPA) is a single-stranded DNA-binding protein that
      is composed of subunits of 70, 32, and 14 kDa. This heterotrimeric complex is
      required for multiple processes in DNA metabolism including DNA replication, DNA
      repair, and recombination. Previous studies have suggested that the 616 amino
      acid, 70-kDa subunit of RPA (RPA 70) is composed of multiple
      structural/functional domains. We used a series of N-terminal deletions of RPA70
      to define the boundaries of these domains and elucidate their functions. Mutant
      RPA complexes missing residues 1-168 of RPA70 bound ssDNA with high affinity and
      supported SV40 replication in vitro. In contrast, deletions extending beyond
      residue 168 showed a decreased affinity for ssDNA and were inactive in SV40 DNA
      replication. When residues 1-381 were deleted, the resulting truncated RPA70 was
      unable to bind ssDNA but still formed a stable complex with the 32- and 14-kDa
      subunits of RPA. Thus, the C-terminal domain of RPA70 is both necessary and
      sufficient for RPA complex formation. These data indicate that RPA70 is composed
      of three functional domains: an N-terminal domain that is not required for ssDNA
      binding or SV40 replication, a central DNA-binding domain, and a C-terminal
      domain that is essential for subunit interactions. For all mutant complexes
      examined, both phosphorylation of the 32-kDa subunit of RPA and the ability to
      support T antigen-dependent, origin-dependent DNA unwinding correlated with ssDNA
      binding activity.

PMID- 8756713
TI  - Fatty acid synthase: in vitro complementation of inactive mutants.
AB  - The animal fatty acid synthase is a dimer of identical, multifunctional 272 kDa
      subunits oriented antiparallel such that two centers for fatty acid synthesis are
      formed at the subunit interface. In order to clarify the interdomain and
      intersubunit communications necessary for the operation of the two centers, we
      have explored the possibility of reassembling catalytically-active fatty acid
      synthase heterodimers from pairs of inactive dimers carrying mutations in
      different functional domains. To this end, rat fatty acid synthase mutants,
      defective in either the beta-ketoacyl synthase, C161T or K326A (KS- FAS), or the
      acyl carrier protein, S2151A (ACP- FAS), domains, were engineered by site
      directed mutagenesis, expressed in insect Sf9 cells using a baculovirus
      expression system, and purified. A novel procedure was devised to facilitate
      rapid production and isolation of a population of mixed mutant dimers that had
      undergone randomization of its constituent subunits. Homodimeric mutants (KS-
      FAS/KS- FAS and ACP- FAS/ACP- FAS) and KS- FAS heterodimers consisting of paired
      C161T and K326A mutant subunits were unable to synthesize fatty acids, confirming
      the essential nature of residues C161, K326, and S2151A. However, KS- FAS/ACP-
      FAS heterodimers regained partial activity. Formation of these heterodimers
      necessitated prior dissociation and reassociation of the homodimers, indicating
      that the rate of spontaneous exchange of subunits in the dimer is negligible. The
      formation of catalytically-active heterodimers from pairs of inactive,
      complementary homodimers affords a useful method for testing the validity of the
      current model for the multifunctional complex.

PMID- 8756714
TI  - Versatility of heme coordination demonstrated in a fungal peroxidase. Absorption
      and resonance Raman studies of Coprinus cinereus peroxidase and the Asp245-->Asn
      mutant at various pH values.
AB  - The pH dependence of the electronic absorption and resonance Raman (RR) spectra
      of FeIII and FeII forms of Coprinus cinereus peroxidase (CIP) and its Asp245-
      >Asn (D245N) mutant has been examined in detail. The spectral data were obtained
      in the pH range 3.8-12.0. These spectra were used to assess the spin and ligation
      states of the heme via the porphyrin marker band frequencies and the wavelengths
      of the absorption maxima, especially that of the band (CT1) due to the charge
      transfer from the porphyrin to the heme iron via the a' 2u(pi)-->eg (d pi)
      electronic transition. The RR spectra were obtained by using different excitation
      wavelengths and polarized light. The data obtained for ferric CIP show that two
      pH-induced structural transitions exist. At acid pH the Soret and the CT1
      absorption maxima occur at 394 and 652 nm, respectively, compared with the values
      of 403 and 649 nm observed at neutral pH. The electronic data indicate that at
      acid pH the proximal Fe-Im bond might be weakened or ruptured, and the RR spectra
      show a new species (5-c HS) different from the normal neutral 5-coordinate high
      spin (5-c HS) heme. At pH 12.0, the protein converts to a 6-coordinate low-spin
      (6-c LS) heme with a hydroxyl ligand coordinated in the sixth position of the
      heme iron and strongly hydrogen-bonded with the positively charged guanidinium
      group of the distal Arg51 residue. Replacement of the aspartate carboxylate group
      of Asp245, which acts as hydrogen-bond acceptor to the proximal His183 ligand of
      the heme Fe, with a carboxamide group of an asparagine residue has a profound
      influence on the heme coordination. The RR spectra of the Fe(II) form of this
      mutant at both neutral and alkaline pH values show a band at 204 cm-1 assigned to
      the Fe-His stretch associated with a fairly weak or non-hydrogen-bonded
      imidazole. The ferric form of the mutant shows a great variability in
      coordination and spin states upon pH titration. Between pH 8.8 and 3.8 the
      spectra are mainly characteristic of a 6-coordinate high-spin heme, presumably
      with a water molecule bound on the distal side of the Fe atom. The pKa of the
      alkaline transition of the mutant is much lower than that of the wild-type
      protein. At pH 10.0 the D245N mutant is in its final alkaline form, which
      markedly differs from that of the parent enzyme. The spectral data indicate that
      the majority of the protein has 5-coordinate high-spin heme (5-c HS), with the Fe
      His 183 bond broken and the distal axial coordination site of the heme iron
      occupied by a hydroxyl group, which is strongly hydrogen-bonded with distal
      Arg51. Therefore, the Asp245-->Asn mutation on the proximal side results in the
      breakage of the Fe-His bond at alkaline pH.

PMID- 8756715
TI  - Peptide-surface association: the case of PDZ and PTB domains.

PMID- 8756716
TI  - Epithelial M cells: gateways for mucosal infection and immunization.

PMID- 8756717
TI  - From glycogen to amylopectin: a model for the biogenesis of the plant starch
      granule.

PMID- 8756718
TI  - Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis.

PMID- 8756719
TI  - Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply
      exposed individuals to HIV-1 infection.
AB  - Rare individuals have been multiply exposed to HIV-1 but remain uninfected. The
      CD4+ T-cells of two of these individuals, designated EU2 and EU3, are highly
      resistant in vitro to the entry of primary macrophagetropic virus but are readily
      infectable with transformed T-cell line adapted viruses. We report here on the
      genetic basis of this resistance. We found that EU2 and EU3 have a homozygous
      defect in CKR-5, the gene encoding the recently described coreceptor for primary
      HIV-1 isolates. These individuals appear to have inherited a defective CKR-5
      allele that contains an internal 32 base pair deletion. The encoded protein is
      severely truncated and cannot be detected at the cell surface. Surprisingly, this
      defect has no obvious phenotype in the affected individuals. Thus, a CKR-5 allele
      present in the human population appears to protect homozygous individuals from
      sexual transmission of HIV-1. Heterozygous individuals are quite common
      (approximately 20%) in some populations. These findings indicate the importance
      of CKR-5 in HIV-1 transmission and suggest that targeting the HIV-1-CKR-5
      interaction may provide a means of preventing or slowing disease progression.

PMID- 8756720
TI  - Ku86-deficient mice exhibit severe combined immunodeficiency and defective
      processing of V(D)J recombination intermediates.
AB  - Ku is a heterodimeric DNA end binding complex composed of 70 and 86 kDa subunits.
      Here, we show that Ku86 is essential for normal V(D)J recombination in vivo, as
      Ku86-deficient mice are severely defective for formation of coding joints. Unlike
      severe combined immunodeficient (scid) mice, Ku86-deficient mice are also
      defective for signal joint formation. Both hairpin coding ends and blunt full
      length signal ends accumulate. Contrary to expectation, Ku86 is evidently not
      required for protection of either type of V(D)J recombination intermediate.
      Instead, V(D)J recombination appears to be arrested after the cleavage step in
      Ku86-deficient mice. We suggest that Ku86 may be required to remodel or
      disassemble DNA-protein complexes containing broken ends, making them available
      for further processing and joining.

PMID- 8756721
TI  - XTcf-3 transcription factor mediates beta-catenin-induced axis formation in
      Xenopus embryos.
AB  - XTcf-3 is a maternally expressed Xenopus homolog of the mammalian HMG box factors
      Tcf-1 and Lef-1. The N-terminus of XTcf-3 binds to beta-catenin. Microinjection
      of XTcf-3 mRNA in embryos results in nuclear translocation of beta-catenin. The
      beta-catenin-XTcf-3 complex activates transcription in a transient reporter gene
      assay, while XTcf-3 by itself is silent. N-terminal deletion of XTcf-3 (delta N)
      abrogates the interaction with beta-catenin, as well as the consequent
      transcription activation. This dominant-negative delta N mutant suppresses the
      induction of axis duplication by microinjected beta-catenin. It also suppresses
      endogenous axis specification upon injection into the dorsal blastomeres of a 4
      cell-stage embryo. We propose that signaling by beta-catenin involves complex
      formation with XTcf-3, followed by nuclear translocation and activation of
      specific XTcf-3 target genes.

PMID- 8756722
TI  - Complementary and mutually exclusive activities of decapentaplegic and wingless
      organize axial patterning during Drosophila leg development.
AB  - Growth and patterning of the Drosophila leg are organized by three secreted
      proteins: Hedgehog (Hh), Wingless (Wg), and Decapentaplegic (Dpp). Hh is secreted
      by posterior cells; it acts at short range to induce dorsal anterior cells to
      secrete Dpp and ventral anterior cells to secrete Wg. Here we show that the
      complementary patterns of dpp and wg expression are maintained by mutual
      repression: Dpp signaling blocks wg transcription, whereas Wg signaling
      attenuates dpp transcription. We also show that this mutual repression is
      essential for normal axial patterning because it ensures that the dorsalizing and
      ventralizing activities of Dpp and Wg are restricted to opposite sides of the leg
      primordium and meet only at the center of the primordium to distalize the
      appendage.

PMID- 8756723
TI  - Hedgehog, transmitted along retinal axons, triggers neurogenesis in the
      developing visual centers of the Drosophila brain.
AB  - The development of the visual centers of the Drosophila brain is tightly
      regulated by the ingrowth of retinal axons from the developing eye. In the first
      optic ganglion, the lamina, arriving retinal axons trigger the precursors of
      their synaptic partners to complete a final cell division and commence neural
      differentiation. The secreted product of the hedgehog gene regulates the temporal
      assembly of photoreceptor precursor cells into ommatidial clusters in the
      compound eye. Here, we show that Hedgehog is transmitted along the retinal axons
      to serve as the inductive signal in the brain. Hedgehog acts in the first of two
      retinal axon-mediated steps in the assembly of lamina synaptic cartridges. These
      observations provide a novel insight into the molecular interactions that
      orchestrate the assembly of neural precursor cells into precise synaptic
      circuits.

PMID- 8756724
TI  - The SCARECROW gene regulates an asymmetric cell division that is essential for
      generating the radial organization of the Arabidopsis root.
AB  - In the Arabidopsis root meristem, initial cells undergo asymmetric divisions to
      generate the cell lineages of the root. The scarecrow mutation results in roots
      that are missing one cell layer owing to the disruption of an asymmetric division
      that normally generates cortex and endodermis. Tissue-specific markers indicate
      that a heterogeneous cell type is formed in the mutant. The deduced amino acid
      sequence of SCARECROW (SCR) suggests that it is a member of a novel family of
      putative transcription factors. SCR is expressed in the cortex/endodermal initial
      cells and in the endodermal cell lineage. Tissue-specific expression is regulated
      at the transcriptional level. These results indicate a key role for SCR in
      regulating the radial organization of the root.

PMID- 8756725
TI  - The immunophilin FKBP12 functions as a common inhibitor of the TGF beta family
      type I receptors.
AB  - The immunophilin FKBP12 is an evolutionarily conserved abundant protein; however,
      its physiological roles remain poorly defined. Here we report that FKBP12 is a
      common cytoplasmic interactor of TGF beta family type I receptors. FKBP12 binds
      to ligand-free TGF beta type I receptor, from which it is released upon a ligand
      induced, type II receptor mediated phosphorylation of the type I receptor.
      Blocking FKBP12/type I receptor interaction with FK506 nonfunctional derivatives
      enhances the ligand activity, indicating that FKBP12 binding is inhibitory to the
      signaling pathways of the TGF beta family ligands. Overexpression of a
      myristylated FKBP12 in Mv1Lu cell specifically inhibits two separate pathways
      activated by TGF beta, and two point mutations on FKBP12 (G89P, I90K) abolish the
      inhibitory activity of FKBP12, suggesting that FKBP12 may dock a cytoplasmic
      protein to the type I receptors to inhibit TGF beta family mediated signaling.

PMID- 8756726
TI  - GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein
      alpha subunits.
AB  - A novel class of regulators of G protein signaling (RGS) proteins has been
      identified recently. Genetic evidence suggests that RGS proteins inhibit G
      protein-mediated signaling at the level of the receptor-G protein interaction or
      the G protein alpha subunit itself. We have found that two RGS family members,
      GAIP and RGS4, are GTPase-activating proteins (GAPs), accelerating the rate of
      GTP hydrolysis by Gi alpha 1 at least 40-fold. All Gi subfamily members assayed
      were substrates for these GAPs; Gs alpha was not. RGS4 activates the GTPase
      activity of certain Gi alpha 1 mutants (e.g., R178C), but not others (e.g.,
      Q204L). The GAP activity of RGS proteins is consistent with their proposed role
      as negative regulators of G protein-mediated signaling.

PMID- 8756727
TI  - Cdc53 targets phosphorylated G1 cyclins for degradation by the ubiquitin
      proteolytic pathway.
AB  - In budding yeast, cell division is initiated in late G1 phase once the Cdc28
      cyclin-dependent kinase is activated by the G1 cyclins Cln1, Cln2, and Cln3. The
      extreme instability of the Cln proteins couples environmental signals, which
      regulate Cln synthesis, to cell division. We isolated Cdc53 as a Cln2-associated
      protein and show that Cdc53 is required for Cln2 instability and ubiquitination
      in vivo. The Cln2-Cdc53 interaction, Cln2 ubiquitination, and Cln2 instability
      all depend on phosphorylation of Cln2. Cdc53 also binds the E2 ubiquitin
      conjugating enzyme, Cdc34. These findings suggest that Cdc53 is a component of a
      ubiquitin-protein ligase complex that targets phosphorylated G1 cyclins for
      degradation by the ubiquitin-proteasome pathway.

PMID- 8756728
TI  - The signal-dependent coactivator CBP is a nuclear target for pp90RSK.
AB  - We have examined the mechanism by which growth factor-mediated induction of the
      Ras pathway interferes with signaling via the second messenger cAMP. Activation
      of cellular Ras with insulin or NGF stimulated recruitment of the S6 kinase
      pp90RSK to the signal-dependent coactivator CBP. Formation of the pp90RSK-CBP
      complex occurred with high stoichiometry and persisted for 6-8 hr following
      growth factor addition. pp90RSK specifically recognized the E1A-binding domain of
      the coactivator CBP. In addition, like E1A, binding of pp90RSK to CBP was
      sufficient to repress transcription of cAMP-responsive genes via the cAMP
      inducible factor CREB. By contrast with its effects on the cAMP pathway,
      formation of the pp90RSK-CBP complex was required for induction of Ras-responsive
      genes. These results provide a demonstration of cross-coupling between two
      signaling pathways that occurs at the level of a signal-dependent coactivator.

PMID- 8756729
TI  - Linker histone H1 regulates specific gene expression but not global transcription
      in vivo.
AB  - In a linker histone H1 knockout strain (delta H1) of Tetrahymena thermophila, the
      number of mature RNAs produced by genes transcribed by pol I and pol III and of
      most genes transcribed by pol II remains unchanged. However, H1 is required for
      the normal basal repression of a gene (ngoA) in growing cells but is not required
      for its activated expression in starved cells. Surprisingly, H1 is required for
      the activated expression of another gene (CyP) in starved cells but not for its
      repression in growing cells. Thus, H1 does not have a major effect on global
      transcription but can act as either a positive or negative gene-specific
      regulator of transcription in vivo.

PMID- 8756730
TI  - Function of E. coli RNA polymerase sigma factor sigma 70 in promoter-proximal
      pausing.
AB  - The sigma factor sigma 70 of E. coli RNA polymerase acts not only in initiation,
      but also at an early stage of elongation to induce a transcription pause, and
      simultaneously to allow the phage lambda gene Q transcription antiterminator to
      act. We identify the signal in DNA that induces early pausing to be a version of
      the sigma 70 -10 promoter consensus, and we show that sigma 70 is both necessary
      for pausing and present in the paused transcription complex. Regions 2 and 3 of
      sigma 70 suffice to induce pausing. Since pausing is induced by the nontemplate
      DNA strand of the open transcription bubble, we conclude that RNA polymerase
      containing sigma 70 carries out base-specific recognition of the nontemplate
      strand as single stranded DNA. We suggest that sigma 70 remains bound to core RNA
      polymerase when the -10 promoter contacts are broken, and then moves to the pause
      inducing sequence.

PMID- 8756731
TI  - Base-specific recognition of the nontemplate strand of promoter DNA by E. coli
      RNA polymerase.
AB  - RNA polymerase recognizes its promoters through base-specific interaction between
      defined segments of DNA and the sigma subunit of the enzyme. This interaction
      leads to separation of base pairs and exposure of the template strand for RNA
      synthesis. We show that base-specific recognition by the sigma 70 holoenzyme in
      this process involves primarily nontemplate strand bases in the -10 promoter
      region. We suggest that melting involves the persistence of these contacts as the
      bound duplex (closed) form is converted to the single-stranded (open) form of the
      enzyme-promoter complex.

PMID- 8756732
TI  - Maturation pathways for E. coli tRNA precursors: a random multienzyme process in
      vivo.
AB  - tRNA maturation consists of the specific removal of precursor sequences from both
      the 5' and 3' termini of an initial RNA transcript. How this is accomplished has
      heretofore not been ascertained in any system. Using Northern analysis of RNA
      isolated from a variety of RNase-deficient E. coli strains, we have identified
      the processing intermediates that accumulate in the absence of specific
      processing nucleases. From this information we have established the maturation
      pathways for 12 different E. coli tRNAs including the specific role of each of
      the relevant RNases in the process. The surprising conclusion from this work is
      that tRNA maturation is a stochastic process that lacks a defined order and that
      can proceed with a variety of alternative 3' processing nucleases.

PMID- 8756733
TI  - [Pharmacologic treatment of mild proliferation of prostatic cancer].
AB  - In the paper, pathophysiological and clinical foundations of modern conservative
      therapy of mild proliferation of prostatic cancer are discussed in a short
      outline. The problems of treatment with hormonal and non-hormonal preparations
      are presented against the background of the mechanism of action of
      pharmacological preparations. The drugs, their dosage, effectiveness and also
      side effects are discussed. The importance is stressed of the drugs blocking the
      alpha-1 adrenergic receptors in the treatment of mild proliferation of prostatic
      cancer with additional beneficial mechanisms of action for the organism.

PMID- 8756734
TI  - [Results of tests with clomiphene and choriogonadotropin in men with
      oligozoospermia treated with longterm antiestrogens].
AB  - The evaluation was made of the response to testosterone and oestradiol in the
      test (50 mg twice daily for 10 days) and HCG test (6000 units of Biogonadyl
      through 2 days) performed on 21 normospermic (fertile) males and on patients with
      normogonadotropic, idiopathic oligozoospermia, positively (12 patients) or
      negatively (24 males) reacting to the longterm Clostilbegyt treatment (50 mg
      daily for 240 days). It was shown that patients with oligozoospermia who do not
      react with an increase of spermatozoa during the longterm antioestrogen treatment
      had higher response of oestradiol in the dynamic test (+ 118.9%) than the
      normospermic males (+ 60.8%) or the oligozoospermic who showed positive
      semenologic response to the treatment (+ 58.8%). The similar reaction of
      oestradiol was shown in the HCG stimulation. In the hiperoestrogenism phenomenon
      the authors noticed the cause of lack of positive semenologic effects of the
      longterm antioestrogen treatment.

PMID- 8756735
TI  - [Antithrombin III and alpha 2-antiplasmin in blood of patients operated on for
      benign prostatic hyperplasia].
AB  - The pre- and postoperative activity was studied of antithrombin III (AT III) and
      alpha 2-antiplasmin (alpha 2-AP) in blood of 40 patients subjected to
      transurethral prostatic electroresection due to benign prostatic hyperplasia
      (BPH). For comparison of the obtained results a control group was formed from
      patients with other diseases of the genitourinary system with exception of
      neoplasms. The activity of AT III and alpha 2-AP before the operation was similar
      to that in the control group. Intraoperatively (day 0) and on the first day after
      the operation, a statistically significantly lower activity of AT III and alpha 2
      AP was found in the patients with BPH in relation to the initial value as well as
      to the control group. On day 5 after the operation, normalization of AT III and
      alpha 2-AP activity was found. During operations of the prostate a release occurs
      of thromboplastins and plasminogen activators initiating the activation of blood
      clotting and fibrinolysis. The decrease of activity of AT III and alpha 2-AP
      could be caused by AT III and alpha 2-AP use-up in the process of inhibition of
      the created thrombin and plasmin.

PMID- 8756736
TI  - [Activity of alpha 1-antitrypsin in blood of patients operated on for tumor and
      benign hyperplasia of the prostate].
AB  - The activity of alpha 1-antitrypsin in the blood of the patients with prostatic
      carcinoma and benign prostatic hyperplasia before and after the operation was
      examined. It was observed an increase of alpha 1-antitrypsin in the blood of
      patients with prostatic carcinoma and benign prostatic hyperplasia after the
      operation. In the blood patients of control group an increase of alpha 1
      antitrypsin was observed too. The activity of alpha 1-antitrypsin in prostatic
      carcinoma was the highest during the whole observation period. The similar
      increase of the activity of alpha 1-antitrypsin after the operation in the blood
      of all groups of patients is connected with inflammatory reaction. The highest
      activity of alpha 1-antitrypsin in the blood of patients with prostatic carcinoma
      is the proof that the malignant neoplasm is associated with much more
      inflammatory reaction and the further hormonal treatment can be connected with a
      risk of thromboembolic complications.

PMID- 8756737
TI  - [The effect of many years of hemodialysis therapy on hypophyseal-gonadal axis
      function in males with chronic renal insufficiency].
AB  - The study aims at evaluating an effect of hemodialyses duration on LH, FSH, and
      testosterone secretion in males with chronic renal insufficiency. Secretion of
      these hormones was assessed with LH-RH stimulation test in 41 men with chronic
      renal insufficiency and 15 healthy controls. Increased LH and FSH and decreased
      testosterone serum levels were seen in men with chronic renal insufficiency in
      comparison with healthy controls, independently of hemodialysis therapy duration.
      Duration of the treatment with hemodialyses has no significant effect on LH
      levels. Testosterone and FSH levels were significantly higher in patients treated
      over 50 months than those treated for shorter periods. Reactivity of LH secretion
      in LH-RH stimulation test was lower in patients dialysed for less than 100 months
      whereas in patients dialysed for over 100 months it was normal. Reactivity of
      testosterone secretion was higher in patients dialysed for over 50 months that
      those dialysed for shorter periods of time.

PMID- 8756738
TI  - [Prognostic factors and results of treating 42 patients with nln-seminomatous
      germ cell tumor of the testis].
AB  - In 1984-1988, 42 patients with non-seminomatous germ-cell tumour of the testis
      were treated surgically in combination with chemotherapy. Actually, 21 (50%)
      patients live without any symptoms, 5 (12%) patients with the symptoms during
      treatment whereas 6 (38%) patients died. Survival period of cured patients was 10
      50 months (median 29 months) while still treated patients--5-34 months (median 10
      months). A relationship between clinical outcome and advancement and tumor weight
      was noted. A decrease in the velocity of tumor weight increase with time lapse
      was seen. Inherited defects of the uro-genital tract were diagnosed in 6 (14%)
      patients.

PMID- 8756739
TI  - [Levels of plasminogen and alpha 2-antiplasmin in blood of patients with
      prostatic tumor].
AB  - In the blood of 20 patients with prostatic carcinoma the level of alpha 2
      antiplasmin and plasminogen were examined. The control group consisted of 20
      patients with benign prostatic hyperplasia. The low activity of alpha 2
      antiplasmin in the blood of the patients with prostatic carcinoma was observed.
      The level of plasminogen was similar in both groups and it was in the low part of
      laboratory normal range. We concluded that the low levels of plasminogen and
      alpha 2-antiplasmin were a result of their consumption during activation of
      fibrinolysis process. The measurement of the alpha 2-antiplasmin and plasminogen
      can be useful to predict a risk of bleeding complications in the patients with
      prostatic carcinoma and benign prostatic hyperplasia.

PMID- 8756740
TI  - [Activity of alpha 1-antitrypsin in blood of patients with prostatic tumor].
AB  - The activity of alpha 1-antitrypsin in patients with prostatic carcinoma and
      benign prostatic hyperplasia was examined. The activity of alpha 1-antitrypsin
      was higher in patients with prostatic carcinoma. The higher activity of alpha 1
      antitrypsin is good prognostic sign for patients with prostatic carcinoma because
      it is born of large defense possibilities in these patients against the disease.

PMID- 8756742
TI  - [Activity of protein C in blood of patients with prostatic carcinoma].
AB  - The activity of Protein C in the blood of the patients with prostatic carcinoma
      and benign prostatic hyperplasia was examined. It was observed a slightly
      decrease of activity of protein C in the blood the patients with prostatic
      carcinoma. The observation of the activity of Protein C is useful because it
      allow to differentiate from patients with prostatic carcinoma a group of high
      risk of haemorrhagic complications. The activity of Protein C may be a prognostic
      factor of a progress of a prostatic carcinoma.

PMID- 8756741
TI  - [Tissue type plasminogen activator and its inhibition in blood of patients
      operated on for prostatic carcinoma].
AB  - In 30 patients with prostatic carcinoma a higher of t-PA, a low of PAI-1, alpha 2
      antiplasmin and plasminogen activity with increased fibrin degradation products
      (FDP) level and a short euglobulin lysis time (ELT) were observed. Following
      surgery a further increased of fibrinolytic activity occurred. The activity of t
      PA and PAI-1 were higher than before operation. Apart from that we observed a
      decreased of plasminogen and alpha 2-AP with further increased level of FDP. On 5
      th day the values of examined parameters were similar as before the operation.

PMID- 8756743
TI  - [Irradiation of the bladder in dogs with narrow laser YAG:Nd].
AB  - The authors discuss effects of YAG:Nd laser beam of 35W and exposure time between
      0.4 and 0.8 second on the internal surface of bladder wall in two dogs. Such an
      energy destroyed bladder tissues to not more than a half of their thickness.

PMID- 8756744
TI  - [YAG:Nd laser cw in treatment of precancerous states of the penis].
AB  - In the paper the results are presented of treatment with laser light generated by
      a YAG:Nd cw laser of a patient with Queyrat disease and another patient with
      leukoplakia of the glans penis. As the result of the treatment carried out, the
      lesions revealed during six-month observation regressed completely, leaving no
      scars. No impairment of sexual functions was found in the treated patients.

PMID- 8756745
TI  - [Disseminated intravascular coagulation syndrome with secondary fibrinolysis
      activation in prostatic carcinoma].
AB  - We reported on a 74 year old patients with local advanced prostatic carcinoma.
      Following prostatic surgery an increased bleeding tendency was observed. The
      patients showed clinical and laboratory evidence for consumption coagulopathy
      with hyperfibrinolysis. The laboratory data were: marked decrease of AT III,
      Protein C, increase of thrombin/AT III complex level, fibrin degradation products
      (FDP) and antigen of t-PA. The treatment was ended successful.

PMID- 8756746
TI  - [Kidney carcinosarcoma].

PMID- 8756747
TI  - [Complication due to intraperitoneal dialysis catheter insertion].
AB  - During the last 6 years 300 stylet and Tenckhoff catheters were inserted into the
      peritoneal cavity. In 5 cases an abdominal viscus has been perforated or injured.
      The complications were twice a perforation of bowel, twice a perforation of
      bladder and once an injury of aorta. The authors discussed the therapeutic
      procedure (conservative or operative) and the late consequences of those
      complications.

PMID- 8756748
TI  - [Fibrinolysis process in prostatic carcinoma].

PMID- 8756749
TI  - [Electric stimulation--hope for patients with urinary incontinence].

PMID- 8756750
TI  - [A trial use of the variable magnetic field in the symptomatic treatment of
      multiple sclerosis].

PMID- 8756751
TI  - [Treatment of prostatic carcinoma--controversies].

PMID- 8756752
TI  - [Dr. Wilhelm Malcz as medical counsel for the Polish Kingdom (1831-1852)].

PMID- 8756754
TI  - A strategy for immunohistochemical signal enhancement by end-product
      amplification.
AB  - We report a novel strategy, called end-product (EP) amplification, capable of
      enhancing the sensitivity of immunohistochemical procedures by about an order of
      magnitude or more. The strategy employs an antibody (anti-EP) to the product
      generated by the action of horseradish peroxidase on 3,3'-diaminobenzidine (DAB),
      and can be extended to the products of other enzymes as well, e.g., alkaline
      phosphatase. Amplification is the consequence of the ability of anti-EP to detect
      the multiplicity of product moelcules resulting from the turnover of substrate by
      a single enzyme molecule. The subsequent detection of anti-EP was by biotinylated
      goat anti-rabbit antibody, followed by avidin-peroxidase and DAB or by avidin
      alkaline phosphatase and Vector Red. Further amplification can be accomplished by
      repeated cycles of the protocol. Anti-EP was produced by immunization with a
      bovine serum albumin (BSA) conjugate of a soluble polymer of DAB, prepared by a
      carefully controlled reaction of DAB with horseradish peroxidase and hydrogen
      peroxide. Coupling to BSA (and to RSA) was accomplished with glutaraldehyde. The
      titer of anti-EP was established by ELISA. Formalin-fixed, paraffin-embedded
      sections of five cases of Hodgkin's disease and five tonsils with follicular
      hyperplasia were immunolabeled for the following lymphoid markers: CD3, CD20,
      CD30, CD45RA, and CD68. EP amplification with anti-EP was also applied to cases
      of CMV pneumonia and cerebral toxoplasmosis to determine whether this procedure
      could improve detection of the infectious agents. Immunolabeling of the primary
      antibody was performed by the avidin-biotin-peroxidase technique with DAB as the
      reaction substrate. The specificity of EP amplification was tested by
      demonstrating binding of anti-EP with Vector Red with the generation of a
      fluorescence end-point. There was complete congruence in the distribution of the
      DAB signal and the red immunofluorescence representing EP amplification. The
      intensity of the DAB signal was increased as much as 16-fold by EP amplification,
      making possible a reduction in the amount of the primary antibody by as much as
      85-90%. Sensitivity also increased with respect to weakly expressed antigens and
      low concentrations of infectious agents.

PMID- 8756753
TI  - PYY in developing murine islet cells: comparisons to development of islet
      hormones, NPY, and BrdU incorporation.
AB  - Exhaustive characterizations of antisera to the structurally related peptides
      pancreatic polypeptide (PP), neuropeptide Y (NPY), and peptide YY (PYY) enabled
      us to establish the developmental pattern of these peptides in rat and mouse
      pancreas. PYY was the earliest detectable peptide and was present in all early
      appearing endocrine cell types. NPY appeared later and occurred exclusively in a
      subpopulation of insulin cells, whereas PP cells arose latest. At the earliest
      stage studied, all endocrine cells stored PYY. Most of these cells also contained
      glucagon. Subsequently, the endocrine cells comprised glucagon+PYY cells and
      glucagon+PYY+insulin cells. Later, cells storing either only insulin or
      insulin+PYY appeared. Quantitations of the relative numbers of these cell
      populations during development were consistent with a precursor role of triple
      positive (insulin+glucagon+PYY) cells. Moreover, bromodeoxyuridine (BrdU)
      injections at E15.5 showed that a large percentage of triple-positive cells were
      in S-phase and therefore were actively dividing, whereas almost no pure insulin
      cells or insulin+PYY cells synthesized DNA at this time. These results suggest
      that PYY-positive endocrine cells may represent precursors for mature islet
      cells.

PMID- 8756755
TI  - Nonradioactive in situ hybridization for detection of mRNAs encoding for
      peroxisomal proteins: heterogeneous hepatic lobular distribution after treatment
      with a single dose of bezafibrate.
AB  - We present a nonradioactive in siru hybridization (ISH) protocol for detection of
      mRNAs in rat liver encoding for three peroxisomal proteins: catalase and urate
      oxidase as representatives of high-level abundance mRNAs and trifunctional
      protein (PH) as that of low-level abundance mRNAs. In addition to normal rats,
      animals treated for 24 hr with a single dose of bezafibrate were studied. The use
      of perfusion-fixation with 4% depolymerized paraformaldehyde/0.05% glutaraldehyde
      combined with paraffin embedding and the application of digoxigenin-labeled cRNA
      probes provided optimal cytological resolution and high sensitivity comparable to
      that of radioactive ISH. In parallel experiments, the same digoxigenin-labeled
      cRNA probes were used for Northern and semiquantitative dot-blot analysis of
      isolated RNAs. In control animals, the mRNAs for catalase and urate oxidase were
      uniformly distributed across the liver lobule and were confined to liver
      parenchymal cells. The bile duct epithelial and the sinusoidal cells remained
      negative. The specificity and the high resolution of our protocol were further
      substantiated by reciprocal localization of transcripts for albumin and
      glyceraldehyde-3-phosphate dehydrogenase in different regions of the liver lobule
      and for catalase in the proximal tubules of the renal cortex. Whereas in control
      livers the transcripts for PH were barely detectable, a strong signal was found
      in pericentral hepatocytes of bezafibratetreated animals, corresponding to an 8
      10-fold increase of mRNA detected in dot-blots. In contrast, the urate oxidase
      mRNA was reduced by more than 50%, with diminution of staining in pericentral
      regions of the liver lobule. The mRNA encoding for catalase was only slightly
      affected. Further applications of this protocol should be helpful in elucidation
      of the cell-specific transcriptional regulation of peroxisomal proteins in
      various organs under normal and pathological conditions.

PMID- 8756756
TI  - Quantitation of L-selectin distribution on human leukocyte microvilli by
      immunogold labeling and electron microscopy.
AB  - L-Selectin is a leukocyte cell adhesion receptor that contributes to neutrophil
      (PMN) rolling on activated endothelium at sites of inflammation and mediates
      lymphocyte attachment to high endothelial venules in peripheral lymph nodes.
      Localization of this receptor to the tips of PMN and lymphocyte microvilli has
      been demonstrated. However, its distribution on these cells has not been
      quantified, and its localization on other leukocytes and the morphometry of
      microvilli on different leukocyte subpopulations have not been previously
      examined. In this study, PMN and mononuclear leukocytes were isolated from
      anticoagulated blood by dextran sedimentation and density centrifugation, fixed
      in 2% paraformaldehyde and 0.05% glutaraldehyde, immunogold-labeled for L
      selectin, and embedded in Epon resin. The distribution of L-selectin was
      determined by counting gold particles on the plasma membrane of sectioned cells,
      and the surface microstructure of these cells was surveyed on two-dimensional
      transmission electron micrographs. On average, 78% of PMN, 72% of monocyte, and
      71% of lymphocyte L-selectin was observed on the microvilli, with more variance
      on lymphocytes than the other cell types. Typical PMN and monocyte sections had
      26 microvilli, whereas typical lymphocyte sections had 23. Quantitation of the
      distribution of L-selectin and leukocyte surface topology offers a foundation
      from which to study the requirement of microvilli or microvillus-localized L
      selectin for leukocyte tethering and rolling in model systems that mimic
      microvascular environments.

PMID- 8756757
TI  - Interspecies reactivities of anti-human macrophage monoclonal antibodies to
      various animal species.
AB  - We examined interspecies reactivities of eight anti-human monocyte/macrophage
      monoclonal antibodies (MAbs), Am-3K, PM-2K, X4, X14, Ber-MAC3, GHI/61, EBM/11,
      and KP1, with various animal tissues including rats, guinea pigs, rabbits, cats,
      dogs, goats, pigs, bovines, horses, and monkeys. All MAbs recognized monkey
      macrophages. Pig macrophages were detected by most MAbs except for EBM/11 and
      KP1. Of the eight antibodies, AM-3K showed the widest interspecies reactivity. It
      reacted with macrophages of all animal species examined, except for rats. Western
      blot analysis revealed a similarity in the antigens recognized by AM-3K among
      guinea pigs, rabbits, and humans. Other anti-human MAbs demonstrated distinct
      reactive patterns against macrophages in animals. The immunostaining patterns of
      all of these MAbs in animal tissues were similar to those found in humans,
      although some MAbs, such as AM-3K, EBM/11, and X4, displayed more restricted
      reactivity in animals than in humans. These results indicate that some anti-human
      monocyte/macrophage MAbs are also available for immunohistochemical detection of
      monocyte/macrophages in animal tissues. Among them, AM-3K is considered to be the
      most useful MAb for identifying macrophages in various tissues of animals.

PMID- 8756758
TI  - The impact of fixatives on the binding of lectins to N-acetyl-glucosamine
      residues of human syncytiotrophoblast: a quantitative histochemical study.
AB  - We describe a quantitative histochemical method for demonstration of five N
      acetyl-glucosamine binding lectins in the syncytiotrophoblast of human term
      placenta. The method employs biotinylated lectins and alkaline phosphatase
      conjugated avidin. The alkaline phosphatase activity is detected by using 5-bromo
      4-chloro-indoxyl phosphate as the substrate and nitroblue tetrazolium as the
      capture agent. The effect of 13 fixative solutions on specific lectin binding and
      nonspecific background staining was quantified by microspectrophotometry. Acid
      fixatives or fixatives containing mercuric chloride, e.g., Carnoy's and Zenker's
      fixatives, gave intense specific lectin binding and low background staining.
      Glutaraldehyde, carbodiimide, and ethanol resulted in low specific lectin binding
      and a very high background staining that was mainly due to endogenous placental
      alkaline phosphatase. Lectin binding to N-acetyl-galactosamine, mannose,
      galactose, and fucose was also significantly higher in sections from tissues
      fixed in an acid fixative compared with a neutral buffered fixative. Unfixed
      cryosections revealed a considerably lower degree of specific lectin binding
      compared with sections from fixed tissues. The activity of endogenous placental
      alkaline phosphatase was inhibited dose-dependently by mercuric chloride and
      decreased with L-phenylalanine concentration over the range of 7.8 x 10(-4) M to
      5 x 10(-2) M, after which there was no further inhibition. Calf intestinal-type
      alkaline phosphatase conjugated to avidin was not inhibited by 5 x 10(-2) M L
      phenylalanine. Endogenous placental biotin did not contribute significantly to
      background staining. Despite the high level of placental alkaline phsophatase,
      the intestinal-type alkaline phosphatase can be used as a marker enzyme in the
      sensitive ABC technique, provided that the nonspecific background is measured and
      substracted. Moreover, it is advisable to use an acid- and/or mercuric chloride
      containing fixative and to add L-phenylalanine during incubation steps.

PMID- 8756759
TI  - Direct visualization of copper-metallothionein in LEC rat kidneys: application of
      autofluorescence signal of copper-thiolate cluster.
AB  - We report on the histochemistry of copper-metallothionein (Cu-MT) in the kidneys
      of Long Evans Cinnamon (LEC) rats. We used the visualization principle of
      histochemistry based on the autofluorescence emission from the fluorophore of
      Cu(+)-thiolate clusters in proteins. Intense autofluorescence signals were
      observed with a ring at the outer stripe of the outer medulla. Orange
      fluorescence signals were observed in the nuclei and cytoplasm of proximal
      straight tubular (PST) cells of segment 3 (S3) at the outer stripe of the outer
      medulla, and yellow-orange signals were detected in lysosome-like organelles in
      the proximal convoluted tubule (PCT) cells of segments 1 and 2 (S1 and S2)
      adjacent to the glomeruli in the cortex. These fluorescent materials were
      identified as Cu-MT because both signals were quenched by withdrawing Cu+ or by
      blocking cysteine residues, the distributions of cysteine residues and
      immunoreactive MT showed identical patterns to the localization of the
      fluorescence signals, and the fluorescent proteins containing Cu were eluted at
      the same Kd value of purified Cu-MT by gel filtration chromatography. However, a
      high level of MT mRNA was detected only in the outer stripe of the outer medulla
      where the orange fluorescence signals were detected, but not in the cortex. This
      difference in localization between the protein and the mRNA suggested that
      synthesis of renal MT occurs do novo in the outer stripe of the outer medulla.
      The yellow-orange fluorescent Cu-MT located in the lysosomal organelles at S1 and
      S2 of the PCT cells in the cortex could be Cu-MT of nonrenal origin, i.e., Cu-MT
      transported from other organs.

PMID- 8756761
TI  - Immunolocalization of protein phosphatase type 1 in Paramecium cells using
      antibodies against recombinant protein and peptides.
AB  - We localized protein phosphatase Type 1 (PP1) in Paramecium cells using
      antibodies (specified on Western blots) against recombinant protein, amino- or
      carboxy-terminal peptides, or peptide segments containing both terminals and an
      intermediate segment. Cell fractionation and ELISA revealed high PP1
      concentrations in cilia, corresponding to observations by immunofluorescence and
      immunogold labeling analyses. We compared ELISA results obtained with MnCl2- or
      detergent-mediated deciliation and immunolocalizations obtained with digitonin
      and saponin- or detergent-mediated permeabilization. We observed that detergents
      at too high concentrations can displace the antigen from its original position.
      Quantitative evaluation of immunogold labeling revealed a predominant
      localization of PP1 in cilia, notably in the narrow space between the membrane
      and the outer microtubule doublets, as ascertained by immunogold labeling of
      Lowicryl sections obtained after rapid freezing and freeze-substitution. This
      localization to the periphery of cilia is compatible with previous suggestions of
      PP1 involvement in ciliary beat regulation, notably of cilia on the free cell
      surface. Immunolabeling occurs along the entire length of surface cilia. Despite
      much higher PP1 concentrations in cilia, ELISA values for absolute PP1 content
      were considerably higher in deciliated cells. This may indicate still other
      functional aspects of PP1. Along these lines, we also discuss the differences
      observed when immunochemical and enzymatic data are compared.

PMID- 8756760
TI  - Latent transforming growth factor-beta 1 and its binding protein are components
      of extracellular matrix microfibrils.
AB  - We studied the localization of latent transforming growth factor-beta 1 (TGF-beta
      1) and its binding protein (LTBP-1) in the extracellular matrix of cultured human
      fibroblasts by immunofluorescence and immunoelectron microscopy.
      Immunofluorescence of confluent fibroblast cultures indicated that LTBP-1
      localizes to extracellular fibrillar structures resembling fibronectin-collagen
      matrix. Similar fibrillar structures were detected in cells stained with
      antibodies specific for TGF-beta 1 propeptide (beta 1-LAP). Both LTBP-1 and beta
      1-LAP colocalized with fibronectin in double immunofluorescence analysis. These
      fibrillar structures were resistant to extraction with sodium deoxycholate, which
      is further evidence that LTBP-1 and large latent TGF-beta 1 complexes are
      integral components of the extracellular matrix. SV-40-transformed human
      fibroblasts lacked extracellular LTBP-1 fibers. EM analysis revealed
      approximately 10-nm-thick microfibrils that were labeled by anti-LTBP at 90-140
      nm intervals. In addition, LTBP-1 was found in structures that were heavily
      labeled for fibronectin. The accumulation of LTBP-1 in the fibronectin matrix
      could be reconstituted in vitro. When isolated matrix components were immobilized
      on nitrocellulose and incubated with fibroblast conditioned medium, LTBP-1 from
      the medium associated with cellular fibronectin but not with heparan or
      chondroitin sulfate, vitronectin, tenascin, laminin, or collagen I or IV. The
      association of LTBP-1 with cellular fibronectin was abolished by treatment of the
      medium with plasmin, which cleaves LTBP-1 and inhibits its assembly to matrix.
      The present results indicate that latent TGF-beta 1 complexes are components of
      the extracellular matrix and suggest that alterations of the pericellular matrix
      could result in aberrant TGF-beta signaling.

PMID- 8756762
TI  - Transient expression of collagen type XIV during muscle development and its
      reappearance after denervation and degeneration.
AB  - In the formation of muscle pattern, the architectural arrangement is believed to
      be controlled by the local connective tissue cells. In this study we examined the
      immunohistological localization of Type XIV collagen recognized by a monoclonal
      antibody, MAb DBM, in embryonic chick hind limbs from stage (St.) 27 to 2 weeks
      post hatching. DBM staining was transiently observed in the epimysium from St.
      30, in the perimysium of the dorsal region from St. 37, and in the entire
      perimysium from St. 39. After hatching, DBM staining was notably diminished in
      both epimysium and perimysium. In contrast, DBM staining and in situ
      hybridization signals for Type XIV collagen mRNA increased in the muscle
      connective tissues after denervation and around the regenerating muscle fibers.
      Therefore, Type XIV collagen expression appears to coincide with muscle activity
      and muscle regenerating conditions, and Type XIV collagen is considered to play
      roles in muscle development and regeneration.

PMID- 8756763
TI  - Immunohistochemical localization of mouse Clara cell 10-KD protein using
      antibodies raised against the recombinant protein.
AB  - To investigate the developmental regulation of the mouse Clara cell 10-KD protein
      (mCC10), we raised an antibody against the recombinant mCC10 protein. The coding
      region for the mature mCC10 protein was placed in frame with the glutathione-S
      transferase gene in the pGEX2-T bacterial expression vector. The GST-mCC10 fusion
      protein was expressed in E. coli DH5 alpha cells. The fusion protein was purified
      and eluted using glutathione-Sepharose beads. The GST-mCC10 fusion protein was
      injected into rabbits to raise antibodies. The rabbit anti-mCC10 antibody was
      tested by immunoblot analysis using both purified protein as well as extracts of
      lung, liver, and uterus. The antibodies produced were used in
      immunohistochemistry and immunoelectron microscopy to detect the cellular
      localization of this protein in the above organs. This anti-mCC10 antibody will
      be useful for future investigation of the developmental biology of the lung.

PMID- 8756765
TI  - [Galactosemia: a problem still unsolved].
AB  - Classical galactosemia is an inherited metabolic disease that results from
      galactose-1-phosphate uridyltransferase deficiency. Untreated galactosemia has
      various manifestations, including central nervous system damage, hepatic failure,
      cataract. Galactose-restricted dietary treatment, the only therapy used in
      galactosemia, brings considerable improvement, especially in the neonatal period.
      However, in the most galactosemic patients this treatment does not prevent
      development of late-onset complications; mental retardation, ovarian failure and
      neurologic disturbances. This article presents a review of contemporary
      hypotheses on possible factors influencing the outcome in galactosemia,
      especially in regard to late-onset complications.

PMID- 8756766
TI  - [Dysrhythmias documented by 48-hour electrocardiographic monitoring in children
      with mitral valve prolapse].
AB  - The association of dysrhythmias with mitral valve prolapse (MVP) in pediatric
      patients was examined by 48-hour ECG monitoring. Fifty unselected children with
      clinical diagnosis of MVP confirmed by echocardiography were studied. Eight (16%)
      patients manifested atrial dysrhythmias. Long runs of junctional rhythm with
      activity were recorded in one patient. Episodes of supraventricular tachycardia
      were recorded in 4 (8%) children. Seventeen (34%) patients had ventricular
      dysrhythmias. In 10 (20%) children, ventricular premature complexes (VPCs) were
      recorded. Four (8%) patients had frequent multifocal VPCs. Ventricular couplets
      were recorded several times in one patient (2%) and nonsustained ventricular
      tachycardia was recorded in two (4%) children. Clinical symptoms did not
      correlate with documented arrythmias. Although the prognostic implications of
      these findings are uncertain, this study demonstrated that potentially serious
      dysrhythmias are common in pediatric patients with MVP. It would appear that
      ambulatory ECG monitoring should be part of the complete evaluation of children
      with MVP.

PMID- 8756764
TI  - GPI-anchored proteins, glycosphingolipids, and sphingomyelin are sequestered to
      caveolae only after crosslinking.
AB  - GPI-anchored proteins, glycosphingolipids, and sphingomyelin are all enriched in
      the detergent-insoluble complex which has been suggested to be purified caveolae.
      I studied the relationship of the molecules with caveolae in cultured cells by
      immunocytochemical methods. In cells reacted with antibodies to various membrane
      proteins and lipids on ice and fixed before applying secondary antibodies,
      labeling did not show concentration in caveolae. In contrast, when cells were
      incubated with the primary and secondary antibodies on ice and then transferred
      to 37 degrees C without fixation, labeled Thy-1.2, beta 2-microglobulin, lactosyl
      ceramide, ceramide tetrahexose, Forssman antigen, and sphingomyelin became
      concentrated in caveolae, whereas labeled transferrin receptor did not. Thy-1.2
      and sphingolipids formed common patches and were sequestered in the same caveolae
      when crosslinked with two primary antibodies simultaneously. On the other hand,
      when either Thy-1.2 alone or lactosyl ceramide alone was crosslinked and
      sequestered to caveolae, the other antigen remained evenly distributed. Caveolar
      sequestration of the antigens occurred in the presence of cytochalasin D,
      nocodazole, or a mixture of the two reagents. The results show that not only GPI
      anchored proteins but also glycosphingolipids and sphingomyelin are sequestered
      in caveolae only after crosslinking, and that the sequestration does not require
      the intact cytoskeleton.

PMID- 8756767
TI  - [Arrhythmias in children with mitral valve prolapse syndrome].
AB  - The aim of the study is analysis of arrhythmia in children with mitral valve
      prolapse syndrome. The study includes 45 children with MVP, 16 boys and 29 girls
      from the district of Bydgoszcz. Their age ranged from 9 to 16 with an average of
      12.4. The diagnosis was based on clinical examination, and results of noninvasive
      examinations of the cardiovascular system with decisive, echocardiographic
      imaging of the heart. Arrhythmia was analyzed with Holter monitoring using
      Hewlett-Packard equipment and the New Wave Holter program. The record was made
      over a 24-hour period. The control group was chosen from children with negative
      symptoms relating to cardiologic disease, in good general health, and normal ECG
      readings. During ECG monitoring in both groups, no complex arrhythmia forms were
      discovered (according to the Lown scale, above class 3). Individual signs of
      premature heart chamber stimulation were diagnosed in about (40% of both groups.
      Additional heart chamber stimulations (VEB) were registered in children with MVP
      (approximately 62%). Moreover, the children with MVP showed higher maximum heart
      activity.

PMID- 8756768
TI  - [Prenatal echocardiography of aortic stenosis].
AB  - Between 1991-1995 five cases of fetal critical aortic stenosis were diagnosed by
      fetal echocardiography at the Polish Mother's Memorial hospital. The main cause
      for referral for fetal ECHO was fetal ascites detected during routine obstetrical
      ultrasound scan in four cases and positive family history in one case. Pregnant
      women had fetal echocardiography monitoring as in-patients. During the first
      examination, the mean aortic valve size was 3.9 mm, mean shortening fraction of
      LV was 15.8%, mean heart/chest area ratio was 0.51. In one case pharmacological
      treatment with digoxin (due to fetal congestive heart failure) and steroids (to
      stimulate fetal lung maturity) was introduced. Amniocentesis due to severe
      polyhydramnios and fetal ascites drainage were also performed in this case. The
      were 2 fetal demises at 26 and 28 weeks of pregnancy, 3 cesarean section due to
      fetal distress during the first period of labour. The pH of umbilical blood was >
      7.2. The newborns died between days 2-4 of life. CONCLUSIONS: Aortic valve
      stenosis can be diagnosed prenatally. This type of fetal heart defect has a poor
      prognosis.

PMID- 8756769
TI  - [The dependence of serum opsonic activity on fibronectin and alpha- 1 acid
      glycoprotein levels in children with burns].
AB  - The concentration of acute phase proteins following burn is known to increase in
      serum rapidly, while that of fibronectin often decreases. Fibronectin (Fn) has
      been demonstrated to serve as an opsonin involved in the ingestion phase in
      phagocytic process. On the other hand, some acute phase proteins such as alpha-1
      acid glycoprotein (AG) may inhibit phagocytic activity. In our study, the
      phagocytic activity of normal granulocytes was decreased by those sera in which a
      high level of AG was accompanied by a fall in the Fn Level. Attempts to detect a
      possible link between the acute phase response and fibronectin led as to study
      whether fibronectin and AG may interact antagonistically on the phagocytic
      activity of neutrophils. For this reason we calculated the Fn/Ag coefficient. We
      showed that an Fn/Ag coefficient in normal sera equals more than 0.20. The higher
      the coefficient, the better the opsonic activity of sera. We propose here that an
      Fn/AG coefficient may be a useful risk factor for infections in burned patients.

PMID- 8756770
TI  - [Human cytomegalovirus infection in the pre- and postnatal period with special
      regards to routes of infection].
AB  - The clinical course of HCMV infection in newborns and infants was discussed.
      Different routes and sources of infection were analyzed, especially acquired
      infection from the mother excreting the virus in breast milk. The usefulness of
      modern laboratory techniques (PCR to detect HCMV DNA and detection of antigen in
      leucocytes) and the importance of simultaneous tests performed in children and
      their mothers in stating the diagnosis was also evaluated.

PMID- 8756771
TI  - [Analysis of blood of children hospitalized in the Children Memorial Health
      Institute between July 1992 and November 1995].
AB  - A total number of 6840 blood cultures were taken from 1753 patients hospitalized
      in the Children's Memorial Health Institute since 07.1992 to 11.1995. Among 6840
      blood samples 679 (10.2%) were culture positive and 745 microorganisms were
      detected; 83.5% Gram(+) bacteria, 9.1% Enterobacteriaceae rods, 1.6%
      nonfermenters, anaerobes - 3.1% and yeast 2.1%. Fifty two percent of all isolated
      strains were represented by CoNS. These bacteria were isolated mainly from
      children hospitalized in cardiology, cardiosurgery, neurosurgery,
      gastroenterology departments and dialysis unit. We found 68% methicillin
      resistant strains of CoNS. S. aureus was isolated from blood of children on
      parenteral nutrition, peritoneal fluid from patients on CAPD, and from blood of
      children with osteomyelitis/arthritis. Fourty percent of the S. aureus strains
      were methicillin resistant. Nonfermenters and Enterobacteriaceae rods were
      isolated predominantly from ICU and gastroenterology department. High percentage
      of these strains were multiresistant to various antibiotics: penicillins, I and
      II generations cephalosporins, aminoglycosides and others.

PMID- 8756772
TI  - [An assessment of infant morbidity and antibiotic therapy according to the type
      and course of delivery between 1983 and 1993].
AB  - A comparative analysis of single and recurrent infant morbidity according to type
      and course of delivery and to kind of drugs used was performed in this study. A
      total of 3676 infants born between 1983-1993 was examined. This group was divided
      into four groups according to date of delivery 1983-1984, 1985-1987, 1988-1990
      and 1991-1993). A steady were in the number of spontaneous and cesearian
      deliveries was noticed. The number of forceps and vacuum extractor deliveries was
      significantly decreased. A higher morbidity was observed among infants from
      breech and vacuum deliveries and among those from families with numerous
      children. Upper respiratory tract infections and allergic dermatitis occurred
      most frequently. The greathy declining trend of usage for the use of antibiotics
      in upper respiratory tract and urinary tract infections was observed. The use of
      two or more antibiotics per therapy was the most common in brachial and lung
      infections.

PMID- 8756773
TI  - [Polish "ZESPOL" osteosynthesis in diaphyses fractures in children].
AB  - Several variations of 52 original Polish "ZESPOL" osteosynthesis were employed in
      50 children in bone diaphyses fractures treated at the 2nd dept. of Cardiac and
      General Pediatric Surgery. In 3 patients complex treatment was carried out by
      joined teams of 2nd dept. of the Cardiac and General Pediatric Surgery and
      Traumatology Ward of Nieklanska Street Pediatric Provincial Hospital, Warsaw.
      Follow-up period showed no early post-operative complications or bone healing
      disturbances. Excellent functional and cosmetic state of the operated extremities
      was preserved in all cases.

PMID- 8756774
TI  - [Hip joint congenital dysplasia, examination, treatment, ultrasound assessment in
      newborns and infants according to Graf].

PMID- 8756775
TI  - [High resolution computed tomography in the diagnosis of lung disease in a 13
      year-old boy].
AB  - The paper describes a case of a 13-year-old boy, who clinically manifested
      symptoms of respiratory failure. High resolution computed tomography (HRCT) was
      used in diagnosis. It allows evaluate injury of the respiratory system in all
      parts of the lungs and bronchid tree. There was correlation between HRCT and
      bronchoscopy, spirometry and bronchography. We conclude that HRCT was a very
      effective and safe diagnostic method in the presented case.

PMID- 8756776
TI  - [Ethmoiditis with orbital complications in children].
AB  - Five ethmoiditis cases with orbital complications in children aged 3.5 to 6 years
      were analysed. All were treated at almost at the same time in Warsaw hospitals in
      October 1994. Among the five presented cases, four were treated surgically. The
      value of CT examination in diagnosing ethmoiditis is stressed by the authors.

PMID- 8756777
TI  - [Subglottic hemangioma as a rare cause of dyspnea in infants].
AB  - A case of congenital subglottic hemangioma of the larynx in a 7-month-old infant
      is presented. The dominant clinical symptoms were: laryngeal stidor, dyspnoea and
      recurrent obstructive bronchitis and pneumonia with unsatisfactory response to
      treatment. Early diagnosis and proper surgical therapy were life-saving in this
      child.

PMID- 8756778
TI  - [Modern methods in the treatment of cystic fibrosis].

PMID- 8756779
TI  - Glucocorticoid receptors: ATP and cell cycle dependence, phosphorylation, and
      hormone resistance.

PMID- 8756780
TI  - The glucocorticoid receptor protein. A hormone-dependent transcription factor.

PMID- 8756781
TI  - Molecular mechanisms of immunosuppression and anti-inflammatory activities by
      glucocorticoids.

PMID- 8756782
TI  - The epithelium as a target of glucocorticoid action in the treatment of asthma.

PMID- 8756783
TI  - Mechanisms of action of glucocorticoids in asthma.

PMID- 8756784
TI  - Steroid receptor number. Individual variation and downregulation by treatment.

PMID- 8756785
TI  - Induction of corticosteroid resistance in vitro.

PMID- 8756786
TI  - Molecular mechanisms of glucocorticoid resistance/hypersensitivity. Potential
      clinical implications.

PMID- 8756787
TI  - Corticosteroid-resistant asthma. Definitions.

PMID- 8756788
TI  - Mononuclear cells in corticosteroid-resistant asthma.

PMID- 8756789
TI  - Glucocorticoid-resistant asthma. T-lymphocyte defects.
AB  - There is adequate evidence that clinical glucocorticoid resistance in asthma can
      be attributed at least partly to a relative resistance of T cells to inhibition
      by glucocorticoids. Although GR asthma defined according to the present criteria
      represents one end of a spectrum of clinical response, in clinical practice these
      patients would not be exposed for prolonged periods to dosages of glucocorticoids
      sufficient to inhibit their T cells in vivo. A more rational approach to the
      selection of alternative therapy for such patients might be possible when the
      mechanisms of this resistance are identified. In the meantime, there is some
      justification for assessing other drugs that inhibit T cells from patients with
      GR asthma at therapeutic concentrations for their efficacy and risk/benefit
      ratios in clinical practice.

PMID- 8756790
TI  - Steroid resistance in asthma. Molecular mechanisms.

PMID- 8756791
TI  - Corticosteroid resistance in other disease states and tissues.

PMID- 8756792
TI  - Pathology of mild, severe, and fatal asthma.

PMID- 8756793
TI  - Current management of asthma patients with corticosteroid resistance.

PMID- 8756794
TI  - Acid aspiration induced lung injury. New insights and therapeutic options.

PMID- 8756795
TI  - Recognition of obstructive sleep apnea.

PMID- 8756796
TI  - The relationship between wheezing and lung mechanics during methacholine-induced
      bronchoconstriction in asthmatic subjects.
AB  - Wheeze is a classic sign of airflow obstruction but relatively little is known of
      its mechanism of production or its relationship to the development of airflow
      obstruction. We studied eight asthmatic subjects age (mean +/- 5D) 42 +/- 5 yr,
      FEV1 2.46 +/- 0.36 L during an extended, symptom-limited methacholine challenge
      test. Breath sounds were detected by a microphone over the right upper anterior
      chest. Spectral analysis was by a fast Fourier transform algorithm. Mean FEV1
      fell by 51 +/- 14% to 1.28 +/- 0.61 L during the challenge and airways resistance
      increased by 119 +/- 50%. There were no consistent changes in breathing pattern
      or tidal volume during the challenge. Wheeze occurred late in the challenge at
      the highest concentration of methacholine administered and only after expiratory
      tidal flow limitation had been reached. Five subjects developed wheeze on tidal
      breathing, the remaining three only wheezed on deep breathing. Wheezing sounds
      were reproducible between breaths, coefficient of variation of starting sound
      frequency was 4.2% and ending frequency 12%. Mean frequency of expiratory wheezes
      was 669 +/- 100 Hz and inspiratory wheezes 710 +/- 76 Hz. Expiratory wheeze fell
      in pitch during a breath (mean fall in sound frequency 187 +/- 43 Hz) but
      inspiratory wheezes were more variable. Expiratory wheezes occurred late in the
      respiratory cycle at a mean of 58% of the maximal tidal expiratory flow, whereas
      inspiratory wheezes occurred around maximal tidal inspiratory flows, suggesting
      that the mechanisms of production of inspiratory and expiratory wheezes may be
      different. In this model, the presence of wheeze during tidal breathing was a
      sign of severe airflow limitation.

PMID- 8756797
TI  - Inhaled misoprostol blocks guinea pig antigen-induced bronchoconstriction and
      airway inflammation.
AB  - Inhaled E-type prostaglandins (PGE) have been shown to modulate responses to both
      allergic and nonallergic provocation. Misoprostol, a PGE1 analog, was developed
      as an antiulcer agent because it prevents gastrointestinal ulceration. Little is
      known about the effect inhaled misoprostol has on the airway and whether its
      potential antiasthmatic activity would be similar to other PGEs. Nebulizied
      solutions of misoprostol and PGE2 effectively blocked the acute bronchospasm
      caused by a subsequent inhaled antigen challenge in actively sensitized guinea
      pigs. The minimal concentration to result in a significant reduction in specific
      airway resistance was 3 and 30 micrograms/ml for misoprostol and PGE2,
      respectively. Exposure to a 300 micrograms/ml nebulized misoprostol solution
      provided significant protection for 2 h. Eosinophil recovery in bronchoalveolar
      lavage performed 24 h after antigen challenge was significantly reduced by 72%.
      In a chronic model of antigen-induced airway inflammation in which guinea pigs
      are given multiple antigen exposures over a 3-wk period, both misoprostol and its
      free acid-active metabolite 5C-30695 significantly reduced bronchoalveolar lavage
      eosinophils by 50 to 55%. Treatment with TRFK5, a monoclonal antibody to
      interleukin-5, resulted in a 76% decrease in eosinophil recovery. The combination
      of antibronchoconstrictive and anti-inflammatory effects suggests that inhaled
      misoprostol may be an effective treatment for the acute and chronic symptoms of
      asthma.

PMID- 8756798
TI  - Effects of air pollution on the respiratory health of asthmatic children living
      in Mexico City.
AB  - The relation between air pollution and the exacerbation of childhood asthma was
      studied in a panel of 71 children (aged 5 to 7 yr) with mild asthma who resided
      in the northern part of mexico City. During the follow-up, ambient measures of
      particulate matter less than 10 microns (PM10, 24-h average) and ozone (1-h
      maximum) frequently exceeded the Mexican standards for these contaminants. The
      peak expiratory flow rate (PEFR) was strongly associated with PM10 levels and
      marginally with ozone levels. Respiratory symptoms (coughing, phlegm production,
      wheezing, and difficulty breathing) were associated with both PM10 and ozone
      levels. An increase of 20 micrograms/m3 of PM10 was related to an 8% increase in
      lower respiratory illness (LRI) among children on the same day (95% confidence
      interval [CI] = 1.04-1.15), and an increase of 10 micrograms/m3 in the weekly
      mean of particulate matter less than 2.5 microns (PM2.5) was related to a 21%
      increase in LRI (95% CI = 1.08-1.35). A 50 parts per billion (ppb) increase in
      ozone was associated with a 9% increase in LRI (95% CI = 1.03-1.15) on the same
      day. We concluded that children with mild asthma are affected by the high ambient
      levels of particulate matter and ozone observed in the northern part of Mexico
      City.

PMID- 8756799
TI  - Indices of airway inflammation in induced sputum: reproducibility and validity of
      cell and fluid-phase measurements.
AB  - Methods to examine sputum for indices of airway inflammation are evolving. We
      have examined the repeatability and the validity of an improved method to measure
      sputum cells and fluid-phase eosinophil cationic protein (ECP), major basic
      protein (MBP), eosinophil-derived neurotoxin (EDN), albumin, fibrinogen,
      tryptase, and interleukin-5 (IL-5). Sputum was induced with hypertonic saline
      twice within 6 d in 10 healthy subjects, 19 stable asthmatics, and 10 smokers
      with nonobstructive bronchitis. The method included the processing of freshly
      expectorated sputum separated from saliva, treatment with a fixed proportion of
      dithiothreitol 0.1% followed by Dulbecco's phosphate-buffered saline, making
      cytospins, and collecting the supernatant. The reproducibility of measurements,
      calculated by the intraclass correlation coefficient, was high for all indices
      measured with the exception of total cell counts and proportion of lymphocytes.
      Asthmatics, in comparison with healthy subjects and smokers with bronchitis, had
      a higher proportion of sputum eosinophils (median percent 5.2 versus 0.5 and
      0.3), metachromatic cells (0.3 versus 0.07 and 0.08), ECP (1,040 micrograms/L
      versus 288 and 352), MBP (1,176 micrograms/L versus 304 and 160), and EDN (1,512
      micrograms/L versus 448 and 272). Asthmatics differed from healthy subjects, but
      not from smokers with bronchitis, in the proportion of neutrophils (46.9% versus
      24.1%), albumin (704 versus 288 micrograms/mL), and fibrinogen (2,080 versus 440
      ng/mL). Smokers with bronchitis showed a trend for a higher neutrophil count and
      levels of albumin and fibrinogen than healthy subjects. The proportion of sputum
      eosinophils correlated positively with ECP, MBP, EDN, albumin and fibrinogen
      levels, and metachromatic cell counts correlated with tryptase. In asthmatics, IL
      5 correlated with eosinophil counts. There was a significant negative correlation
      between sputum indices and expiratory flows and methacholine PC20. Thus, the
      methods of measuring cell and fluid phase markers in induced sputum used in this
      study are reproducible and valid. They can therefore be used to reliably measure
      these indices of airway inflammation.

PMID- 8756800
TI  - Reactivity to IgE-dependent histamine-releasing activity in asthma or rhinitis.
AB  - We investigated the relation between IgE reactive with histamine-releasing factor
      (HRF) and clinical status in patients with asthma or rhinitis. Sera were used to
      passively sensitize purified, lactic-acid treated basophils. IgE-independent HRF
      due to chemokines was removed from mononuclear cell supernatants with heparin
      Sepharose. IgE-dependent HRF was determined by measuring the increase in
      histamine release between 1 min and 60 min, which was designated delta HRF. HRF
      reactive IgE was demonstrable in nine of 18 patients with allergic asthma, three
      of 19 patients with nonallergic asthma, five of 17 patients with allergic
      rhinitis, and none of 19 control patients. The presence of HRF-reactive IgE was
      associated with: (1) IgE to inhalant allergens; 40% of radioallergosorbent test
      (RAST)-positive individuals versus 8% of RAST-negative individuals were positive
      (OR = 7.8, p < 0.005); (2) bronchial sensitivity to histamine in all asthmatic
      patients (geometric mean PC20: 1.50 versus 0.51 mg/ml; p < 0.005); and (3)
      bronchial sensitivity to histamine in allergic asthmatic patients (geometric mean
      PC20: 1.27 versus 0.37 mg/ml, p < 0.02). These findings support the hypothesis
      that IgE-dependent HRF might contribute to the chronic allergic reaction.

PMID- 8756801
TI  - A placebo-controlled, crossover comparison of salmeterol and salbutamol in
      patients with asthma.
AB  - We compared the effects of salmeterol (Sm) (50 micrograms twice daily) with that
      of salbutamol (Sb) (200 micrograms four times daily) and placebo (P) in patients
      with mild-to-moderate asthma with asthma symptoms and related the effectiveness
      of these therapies between patients who used concurrent inhaled corticosteroids
      (ICS) and those who did not. The study was a 12-wk, multicenter, double-blind,
      placebo-controlled crossover trial with 367 adult asthmatics randomized to each
      trial medication for 4 wk. Inhaled Sb was provided as rescue medication to all
      patients throughout the trial. Only 80% of patients, albeit the majority, were
      receiving maintenance treatment with ICS throughout this trial; this reflects
      practice current in early 1990. Each study day, patients recorded their morning
      and evening peak expiratory flows (PEF), assessment of asthma symptoms, and use
      of rescue medication. Both morning and evening PEF were greater during treatment
      with Sm than with Sb (mean differences between the treatments of 29.8 and 14.3
      L/min, respectively) or P (27.7 and 20.3 L/min, respectively) (p < 0.0001). Sm
      was also more effective than Sb or P in lowering diurnal variation in PEF and
      increasing the percentage of symptom-free days and rescue-free days and nights
      with no sleep disturbance (p < or = 0.0004). Sb was more effective than P in
      increasing evening PEF and the percentage of symptom-free days (p < 0.05) and
      rescue-free days (p < 0.0001). The same clinical superiority of Sm compared with
      Sb and P was observed in those patients using ICS (p < 0.001 for all treatment
      comparisons), and to a greater extent than in those patients not using ICS (i.e.,
      Sm was more effective than Sb and P in just six of the 20 treatment comparisons;
      p < 0.05). In conclusion, Sm 50 micrograms twice daily is effective in the
      management of mild-to-moderate asthma and it further improves asthma control in
      patients already using ICS.

PMID- 8756802
TI  - Outcome of specific bronchial responsiveness to occupational agents after removal
      from exposure.
AB  - A decrease in specific bronchial responsiveness (SBR) could occur after removal
      from exposure to an agent causing occupational asthma as a result of loss of
      immunologic and/or nonspecific bronchial reactivity (NSBR). We studied 15
      subjects with occupational asthma (eight to a high- and seven to a low-molecular
      weight agent, isocyanate in all instances), proved by specific inhalation
      challenges (SIC) done 2 yr or more before. Subjects were reexposed in the same
      way as in the initial SIC: for subjects who did not react, the exposure was
      increased until either an asthmatic reaction occurred or a maximum of 2 h was
      reached. NSBR was assessed before and after SIC. Subjects had a decrease in their
      SBR if the total dose of agent necessary to induce asthmatic reaction was greater
      by twofold compared with the initial SIC. There was a significant improvement in
      NSBR in seven of 15 subjects. Nine of 15 subjects (60%) had a decrease in their
      SBR. Only one had a complete loss of SBR. Changes in NSBR, molecular weight of
      the offending agent, decrease of antibody level against offending agents, or
      duration of exposure at work did not explain the decrease in SBR. We conclude
      that after removal from exposure to the offending agent a majority of subjects
      (60%) show a decrease but a persistence of SBR to high- and low-molecular-weight
      agents.

PMID- 8756803
TI  - The role of atopy in grain dust-induced airway disease.
AB  - To determine whether atopy influences the physiologic or inflammatory response to
      grain dust, we compared spirometric measures of airflow and bronchoalveolar
      lavage (BAL) measures of lower respiratory tract inflammation between
      demographically similar nonatopic (n = 10) and atopic (n = 10) study subjects
      after each of two inhalation exposures: Hanks' balanced salt solution (HBSS) and
      corn dust extract (CDE; 0.4 microgram of endotoxin/kg body weight). Subjects were
      healthy nonsmokers with similar baseline pulmonary function, without bronchial
      hyperreactivity, and had not participated in agriculture. Atopic subjects had two
      or more positive skin responses to 10 common environmental allergens. Both groups
      developed significant airflow obstruction and lower airway inflammation after CDE
      inhalation. Importantly, the magnitude of the post-CDE exposure airflow
      decrements, BAL cellularity, and BAL concentration of tumor necrosis factor-alpha
      (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, and IL-8 did not significantly
      differ between atopics and nonatopics. The concentrations of histamine and
      eosinophils in the BAL fluid were unaffected by CDE inhalation and did not
      significantly differ between atopics and nonatopics. Atopic status does not
      appear to be a significant determinant of airflow obstruction or lower airway
      inflammation following CDE inhalation. Our findings suggest that atopy may play,
      at most, a minor role in the development of grain dust-induced airway disease.

PMID- 8756804
TI  - Endothelin-1 depresses tracheal mucus velocity in ovine airways via ET-A
      receptors.
AB  - Endothelin-1 (ET-1) is a potent constrictor of bronchial smooth muscle, but there
      is limited information on its actions on the airway mucociliary clearance in
      vivo. The purpose of this study was to determine (1) the effect of aerosolized ET
      1 on tracheal mucus velocity (TMV), a marker of mucociliary clearance, in sheep
      and (2) if the ET-1-induced effects were mediated by ET-A or ET-B receptors. To
      measure TMV, radiopaque teflon particles were insufflated into six intubated,
      spontaneously breathing, adult sheep, and the velocity at which these particles
      traveled up the trachea was measured using a previously reported roentgenographic
      technique. After baseline TMV measurements, 50 breaths of either ET-1 (10(-7) M)
      or vehicle (phosphate-buffered saline) were aerosolized into the airways. TMV
      measurements were then obtained over a 2-h period. After exposure to ET-1, mean
      TMV decreased significantly as compared with vehicle, the effects being most
      marked within 30 min after administration (54%, p < 0.05). On subsequent days,
      animals were pretreated with an aerosolized ET-A receptor antagonist (BQ-123) or
      an ET-B receptor antagonist (BQ-788) before exposure to ET-1. When ET-1 was given
      after BQ-123, no significant drop in TMV was noted. In contrast, pretreatment
      with BQ-788 exhibited no protective effect on the decrease in TMV. The ET-1
      effects were not influenced by pretreatment with either the cyclo-oxygenase
      inhibitor indomethacin or the leukotriene receptor antagonist MK-571, indicating
      that ET-1-induced depression in TMV does not involve the activation of
      prostanoids or peptide leukotrienes. Thus, exogenous ET-1 reduces TMV, an in vivo
      effect that is mediated through stimulation of ET-A receptors.

PMID- 8756805
TI  - Matrix metalloproteinases and TIMP in acute respiratory distress syndrome.
AB  - To investigate the implication of extracellular matrix proteinases in acute
      respiratory distress syndrome (ARDS), we determined 92 kD gelatinase (92 G'ase)
      and its natural antagonist, the tissue inhibitor of metalloproteinases-1 (TIMP)
      in bronchoalveolar lavage fluid (BALF) and plasma of 33 intensive care unit (ICU)
      patients presenting with trauma or septic shock. Eleven of these patients
      developed short-course ARDS, nine developed prolonged ARDS, and 13 did not
      progress to ARDS. Ten non-ICU patients served as controls. During the early phase
      of disease, 92 G'ase in BALF of ICU patients was higher than in controls, but
      plasma levels were not different. TIMP was increased in BALF and plasma in ARDS
      as compared with those of patients at risk. The 92 G'ase/TIMP ratio in BALF
      remained elevated in late phases of prolonged ARDS. The high intrapulmonary
      levels of 92 G'ase in patients at risk and with ARDS may reflect increased
      turnover of extracellular matrix in acute lung injury. Increased TIMP may
      interfere with tissue repair and fibrosis by its inhibition of 92 G'ase.
      Interleukin-6 (IL-6) could be involved in enhanced local synthesis of TIMP. The
      balance between 92 G'ase and TIMP may play an important role in lung remodeling,
      which is characteristic of ARDS.

PMID- 8756806
TI  - Comparison between nocturnal nasal positive pressure ventilation combined with
      oxygen therapy and oxygen monotherapy in patients with severe COPD.
AB  - We evaluated the benefits of O2 therapy and nocturnal nasal positive pressure
      ventilation (NPPV) with or without O2 in patients with severe chronic obstructive
      pulmonary disease (COPD). Twelve patients with severe COPD and nocturnal oxygen
      desaturation, who had not been receiving long-term O2 therapy and who could
      tolerate more than 2 wk of NPPV therapy, were enrolled in this study in a stable
      condition. Data on pulmonary function tests (PFTS), arterial blood gases (ABG),
      right and left ventricular ejection fractions (RVEF and LVEF) from nuclear
      medicine studies, and overnight sleep studies were collected at the beginning of
      the study and after each 2 wk of therapy with O2, NPPV, or NPPV with O2. Patients
      received O2 monotherapy or NPPV for sequential 2-wk periods in a randomized,
      cross-over design, followed by 2 wk of NPPV with O2. Hypoxic and hypercapnic
      ventilatory responses (HVR) in the study group, as measured by mouth occlusion
      pressure in the first 100 ms of inspiration against an occluded airway (P0.1),
      were compared with normal controls and repeated after 2 wk of therapy with NPPV
      with O2. The results revealed no significant changes in the percent of each sleep
      stage regardless of the treatment modality. However, sleep efficiency was poorer
      when NPPV was used than when it was not used. NPPV alone did not improve
      nocturnal oxygenation when compared with the baseline sleep study. Oxygen
      monotherapy was better than NPPV therapy for improving nocturnal oxygenation.
      NPPV plus O2 therapy showed no benefits over O2 monotherapy in either RVEF or
      LVEF, ABG, or HVR. In conclusion, for severe COPD patients, O2 therapy is more
      effective than NPPV for improving nocturnal oxygenation.

PMID- 8756807
TI  - Unattended continuous positive airway pressure titration. Clinical relevance and
      cardiorespiratory hazards of the method.
AB  - The high cost of in-laboratory sleep studies and the insufficiency of available
      nights in most sleep laboratories has prompted clinical trials in an attempt to
      find an effective and safe method for continuous positive airway pressure (CPAP)
      titration in the unsupervised home environment. Earlier publications focused on
      the effectiveness of this new method but did not indicate the potential hazard
      and the selection criteria of patients. We accomplished a prospective study to
      evaluate a machine-controlled CPAP titration method in an unselected group of 21
      patients with obstructive sleep apnea (OSA) requiring CPAP therapy. Unattended
      CPAP titrations were completed in the sleep laboratory, followed by conventional
      CPAP titration night. The CPAP levels assessed through automatic titrations
      showed strong agreement with those from the control nights. Fifteen patients had
      no pathologic cardiorespiratory events during machine-controlled titration.
      Undesirable cardiorespiratory complications developed in six patients with
      underlying cardiorespiratory disorder. Two patients had to stop the procedure.
      Two patients needed a reset of the actual pressure to baseline because of central
      apneas and one patient because of high-grade arrhythmia. The machine-controlled
      CPAP titration enabled reliable assessment of an effective pressure and appeared
      to be safe in selected patients with OSA. However, because the method caused
      significant adverse effects in some patients, we recommend that unattended CPAP
      titration not be attempted in patients with underlying cardiorespiratory disease.

PMID- 8756808
TI  - Ultrasonic nebulized in comparison with instilled surfactant treatment of preterm
      lambs.
AB  - To evaluate the efficiency and distribution of ultrasonic nebulized versus
      instilled surfactant in the treatment of surfactant deficiency at varying degrees
      of maturation, twin or triplet lamb fetuses were delivered at 125 to 137 d
      gestational age and received nebulized natural surfactant (Neb Only), instilled
      surfactant followed by a second instilled dose (Inst/Inst), instilled surfactant
      followed by nebulized surfactant (Inst/Neb), or no surfactant (Control). The
      lambs were ventilated for 6 h. Twenty-eight lambs were categorized into two
      groups (low compliance versus moderate compliance) based on initial physiologic
      lung characteristics. Efficiency of deposition of nebulized surfactant directly
      correlated with the compliances and ventilatory efficiency indices measured at 15
      min of age. The low-compliance group (Low Comp) had significantly lower
      efficiency of surfactant deposition (7.6 +/- 1.6%) than did the moderate
      compliance group (Mod Comp) (23.4 +/- 2.5%) (p < 0.01). Overall, instilled
      surfactant had a reasonably homogeneous distribution, whereas nebulized
      surfactant had a less homogeneous distribution, except for the Low Comp, Inst/Neb
      group, which had a distribution pattern similar to that for instilled surfactant.
      The potential for nebulized surfactant therapy for respiratory distress syndrome
      (RDS) may be limited by the nonhomogeneous nature of ventilation in the preterm
      lung.

PMID- 8756809
TI  - Cycle length of periodic breathing in patients with and without heart failure.
AB  - Because apnea length during periodic breathing varies according to the preceding
      increase in ventilation and reduction in PaCO 2, differences in the cycle length
      of periodic breathing among patients with normal and impaired cardiac function
      might be explained by the influence of lung-to-carotid body circulatory delay, as
      reflected by lung-to-ear circulation time (LECT), on hyperpnea length rather than
      on apnea length. It was therefore hypothesized that circulatory delay is an
      important determinant of periodic-breathing hyperpnea length but not apnea
      length. To test this hypothesis, LECT, periodic-breathing cycle length, apnea
      length, and hyperpnea length were compared in 10 patients with idiopathic central
      sleep apnea (ICSA), whose cardiac function was normal, as opposed to 10 with
      Cheyne-Stokes respiration and central sleep apnea (CSR-CSA) in association with
      congestive heart failure (CHF). As compared with ICSA patients, cycle length was
      significantly longer in patients with CSR-CSA (37.3 +/- 3.0 s versus 59.0 +/- 4.9
      s, p < 0.005). This difference was due to significantly longer hyperpnea length
      in the CSR-CSA patients (16.7 +/- 2.8 s versus 36.7 +/- 3.4 s, p < 0.001), since
      apnea length was similar in the two groups. In addition, LECT was longer in the
      CSR-CSA patients (24.3 +/- 2.0 s versus 10.3 +/- 1.0 s, p < 0.001), and
      correlated strongly with cycle length (r = 0.88, p < 0.001) and hyperpnea length
      (r = 0.90, p < 0.001) but not with apnea length. LECT correlated inversely with
      cardiac output (r = -0.72, p < 0.006), indicating that LECT is a valid measure of
      circulatory delay. Thus, circulatory delay is an important determinant of
      hyperpnea length but not of apnea length in patients with ICSA and CSR-CSA.

PMID- 8756810
TI  - Aerosol delivery from a metered-dose inhaler during mechanical ventilation. An in
      vitro model.
AB  - Successful bronchodilator therapy with a metered-dose inhaler (MDI) in intubated,
      mechanically ventilated patients requires adequate delivery of aerosol to the
      lower respiratory tract. We determined the effect of ventilator mode, inspiratory
      flow pattern, humidity, and spontaneous respiratory effort on albuterol delivery
      in a model of the trachea and bronchi. The model was ventilated through an
      endotracheal tube during controlled mechanical ventilation (CMV), assist control
      (AC), pressure support (PS), and continuous positive airway pressure (CPAP),
      separately with a dry and humidified ventilator circuit. Delivery of albuterol
      administered by a MDI and spacer on filter placed at the ends of the bronchi was
      measured by spectrophotometry (246 nm). Under dry conditions and with a frequency
      of 10 breaths/min, albuterol delivery with CMV (VT, 800 ml; 30.3 +/- 3.4%), AC
      (VT, 800 ml; 31.9 +/- 1.3%), PS 10 cm H2O (VT, 700 ml; 28.8 +/- 4.5%), or PS 20
      cm H2O (VT, 800 ml; 30.9 +/- 1.8%) was lower than that observed with simulated
      spontaneous breaths with CPAP (VT, 800 ml; 39.2 +/- 1.4%) (p < 0.01 for all
      modes). Delivery was greater under dry (28.8 to 39%) than under humidified
      conditions (15.9 to 20.2%) (p < 0.005 in all modes). Albuterol delivery showed a
      linear correlation with both inspiratory time and duty cycle (r > 0.91). Lower
      respiratory tract delivery of aerosol from a MDI varied from 4.9 to 39.2%. We
      conclude that in addition to other known factors such as dose, type of spacer,
      and its position the technique of administering MDIs in mechanically ventilated
      patients markedly influences lower respiratory tract aerosol delivery.

PMID- 8756811
TI  - Dose-response to bronchodilator delivered by metered-dose inhaler in ventilator
      supported patients.
AB  - In nonintubated patients, metered-dose inhalers (MDIs) are accepted as the most
      convenient, efficient, and cost effective method of administering inhaled
      bronchodilators. Recent studies have demonstrated the efficacy of MDIs in
      ventilator-supported patients; however, the optimal dose of a bronchodilator from
      a MDI is unknown. We determined the response to increasing doses of albuterol
      administered by a MDI and cylindrical spacer to 12 mechanically ventilated
      patients with chronic obstructive pulmonary disease (COPD). Four, eight, and 16
      puffs of albuterol were given at 15-min intervals. Rapid airway occlusion were
      performed before and at 5-min intervals after albuterol for 80 min. Respiratory
      mechanics were also measured for 60 min in another group of seven patients with
      COPD who received four puffs of albuterol. Significant decrease in airways
      resistance occurred after administration of albuterol (p < 0.001). The decrease
      in airway resistance with four puffs of albuterol was comparable to that observed
      with cumulative doses of 12 puffs (p = 0.12) and 28 puffs (p = 0.25). Heart rate
      increased significantly (p < 0.01) after a cumulative dose of 28 puffs. The
      decrease in airway resistance was sustained for 60 min in the group that received
      only four puffs of albuterol (p < 0.003). In conclusion, four puffs of albuterol
      given by a MDI and spacer provided the best combination of bronchodilator effect
      and safety in stable mechanically ventilated patients with COPD.

PMID- 8756812
TI  - Intermittent enteral feeding: the influence on respiratory and digestive tract
      colonization in mechanically ventilated intensive-care-unit patients.
AB  - Continuous enteral feeding (CEF) has been associated with decreased gastric
      acidity, thereby stimulating gastric colonization and ventilator-associated
      pneumonia (VAP). Intermittent enteral feeding (IEF) could induce a temporary
      increase in gastric acidity and decrease the risk of VAP. We studied the
      influence of IEF (18 h/d) and CEF (24 h/d) on gastric and oropharyngeal
      colonization. Sixty patients were randomized to receive either IEF or CEF, and
      continuous intragastric pH monitoring was performed in 50 patients. Median
      intragastric pH levels were similar before enteral feeding was instituted (pH 2.5
      for CEF and pH 2.4 for IEF), and median pH values increased slightly after
      institution of nutrition (NS). In patients receiving IEF, median pH decreased
      from 3.5 to 2.2 (p = 0.0002) when enteral feeding was discontinued. However,
      despite this, 80% of the patients in both study groups were colonized in the
      stomach after 7 d in study. In addition, colonization rates of the oropharynx and
      trachea, the incidence of VAP, and mortality were similar in both study groups.
      IEF was less well tolerated than CEF. We conclude that almost all patients
      receiving enteral feeding are colonized in the stomach with gram-negative
      bacteria. IEF resulted in a slight decrease in intragastric pH without
      influencing rates of colonization and infection of the respiratory tract.

PMID- 8756813
TI  - Bronchoalveolar lavage for evaluation and management of scleroderma disease of
      the lung.
AB  - Fibrosing alveolitis (FA) is a frequent and often fatal complication of systemic
      sclerosis (SSC). Alveolar inflammation has been recognized as a primary event in
      the pulmonary manifestation of SSC. To evaluate the significance of the
      alveolitis in SSC, we performed bronchoalveolar lavage (BAL) and correlated the
      generated data with changes in lung function over time. Seventy nine SSC patients
      with pulmonary involvement were followed for 56.8 +/- 3.1 wk (mean +/- SEM) with
      a repeat lung function test at the end of the follow-up period. During follow-up,
      38 patients were treated with a systemic immunosuppressive regimen. For
      evaluation, patients were assigned to two groups according to whether their BAL
      cell differential was normal (inactive BAL) or abnormal (active BAL: i.e.,
      polymorphonuclear leukocytes > 5% and/or lymphocytes > 15%). Active BAL was
      associated with more severe lung function impairment than was inactive BAL, and
      patients with active BAL deteriorated during follow-up if untreated. In contrast,
      treated patients with active BAL stabilized or improved. In summary, active
      alveolitis as characterized by BAL is associated with progressive pulmonary
      disease in SSC patients, and a significant positive effect of immunosuppressive
      therapy on the course of pulmonary disease was observed in patients with active
      BAL.

PMID- 8756814
TI  - Controlled trial of oral prednisone in outpatients with acute COPD exacerbation.
AB  - Corticosteroids are often used in the outpatient treatment of acute exacerbation
      of chronic obstructive pulmonary disease (COPD). To date, there are few data
      documenting the benefit of this practice. The objective of this randomized,
      double-blind, placebo-controlled trial was to assess the efficacy of
      corticosteroids in the outpatient treatment of COPD exacerbations. Twenty-seven
      patients presenting with acute COPD exacerbation were studied. In addition to
      continuing their previous medications and increasing their use of beta-agonists,
      patients were randomized to receive a 9-d tapering dose of either oral prednisone
      or placebo. Treatment with prednisone rather than placebo resulted in a more
      rapid improvement in arterial PO2 (PaO2) (1.12 mm Hg/d versus -0.03 mm Hg/day; p
      = 0.002), alveolar-arterial oxygen gradient (A-aDO2) (-1.16 mm Hg/d versus -0.03
      mm Hg/day; p = 0.04), FEV1 (0.05 L/d versus 0.00 L/d; p = 0.006), and peak
      expiratory flow (PEF) (0.15 L/s/d versus 0.04 L/s/d; p = 0.009). Prednisone also
      resulted in fewer treatment failures (p = 0.002) and in a trend toward more rapid
      improvement in dyspnea scale scores. Outpatient treatment of acute COPD
      exacerbation with prednisone accelerates recovery of PaO2, A-aDO2, FEV1, and PEF,
      reduces the treatment failure rate, and improves subjective dyspnea.

PMID- 8756815
TI  - Short-term recombinant human DNase in bronchiectasis. Effect on clinical state
      and in vitro sputum transportability.
AB  - We report a double blind placebo-controlled phase II study of the efficacy and
      safety of nebulized recombinant human DNase (rhDNase) administered for 14 d to
      adults with bronchiectasis not caused by cystic fibrosis. All were in a stable
      clinical state at the commencement of the study, and they received (1) rhDNase
      2.5 mg twice daily, (2) rhDNase once daily, or (3) placebo (excipient only)
      inhalation. The outcome measures were spirometry, subjective quality of
      life/dyspnea, and safety. We also measured the ciliary transportability of the
      sputum expectorated before and after the treatment period, using the mucus
      depleted bovine trachea. The drug was well tolerated, but it produced no
      significant change in any of the outcome variables or in sputum transportability.
      When the drug was incubated with bronchiectatic sputum in vitro, a fall in
      transportability was observed. We discuss possible explanations for the lack of a
      measurable benefit from rhDNase in this study population, which appears to
      contrast with the improvements shown in cystic fibrosis using studies of similar
      design.

PMID- 8756816
TI  - Dissociation of bradykinin-induced plasma exudation and reactivity in the
      peripheral airways.
AB  - To determine if bradykinin, a potential mediator of asthma, acts, at least in
      part, at the level of the peripheral airways, we used a wedged bronchoscope
      technique to study asthmatic and normal subjects. Baseline peripheral airways
      resistance (Rp) was measured in the right upper lobe. Subjects then received
      saline, followed by increasing doses of bradykinin, aerosolized through the
      bronchoscope. Rp was measured after each challenge. At the end of the procedure,
      bronchoalveolar lavage was performed in both the challenged and a control
      segment. Fibrinogen content of recovered lavage fluids was measured as an index
      of plasma exudation. Bradykinin induced a dose-dependent increase in Rp in the
      asthmatics, but did not effect Rp in normal subjects. In asthmatics, there was no
      significant correlation between peripheral airways reactivity and whole lung
      reactivity to bradykinin. Fibronogen increased significantly in both groups after
      bradykinin challenge, and there was no significant difference between
      postchallenge levels for the two groups. Thus, hyperreactivity of the peripheral
      airways in asthmatics is not directly due to plasma exudation. The ability of
      bradykinin to increase peripheral airways resistance in asthmatic, but not in
      normal, subjects is consistent with a role of this peptide as a mediator of
      asthma.

PMID- 8756817
TI  - Lung sound spectra at standardized air flow in normal infants, children, and
      adults.
AB  - To investigate the effect of age and body size on normal lung sounds, we studied
      10 newborn infants within 3 d after birth, nine children between 6 to 8 yr, and
      10 adults between 25 and 37 yr of age. Lung sounds were recorded with a contact
      transducer over the posterior right lower lobe, and air flow was measured at the
      mouth. Computer analysis provided average power spectra of lung sounds at flows
      of 15 ml/s/kg. In children and adults measurements were also made at flows of 30
      ml/s/kg. Lung sounds were referenced to background noise, measured at zero air
      flow. The spectra in infants contained less power below 300 Hz compared with
      children and adults, resulting in significantly higher quartile and spectral edge
      frequencies. Resonances of the thoracic cavity may explain some of the
      differences among the study groups. Sound attenuation above 300 Hz was similar at
      all ages. At increased air flows, lung sounds in children and adults were above
      background noise at frequencies as high as 2,000 Hz. High-frequency expiratory
      lung sounds of low intensity were present in all children and in eight of 10
      adults at increased flows. Normal lung sounds of low intensity are present above
      traditionally accepted frequency limits and warrant further investigation.

PMID- 8756818
TI  - Seasonal variation in sudden infant death syndrome and bronchiolitis--a common
      mechanism?
AB  - The purpose of this study was to compare epidemiologic features of sudden infant
      death syndrome (SIDS) and bronchiolitis and to apply statistical examination in
      order to examine the hypothesis that similar mechanisms could be at work in both
      conditions. The setting was Scotland from 1982 through 1990. We compared 1,211
      deaths from SIDS with 10,058 hospital admissions for bronchiolitis in infancy.
      The comparisons included age, sex ratio, and seasonality. The sex ratios were
      similar (SIDS [M:F]:1.61:1; bronchiolitis: 1.63:1), but age distribution was
      different (chi 2 = 104.6, p < 0.001). When monthly rates throughout the year were
      compared using correlation of residuals from average season variation and by
      autocorrelation of residual series, no significant relationships were found
      between the two conditions (r2 = 0.0004). Once the seasonal pattern common to
      both conditions was accounted for, SIDS was not autocorrelated between months
      whereas bronchiolitis exhibited a high level of autocorrelation indicating an
      epidemic pattern for the latter but not for the former. While a common seasonal
      variation may indicate some shared etiologic factors associated with winter
      season, the two conditions do not appear to be closely related. The hypothesis
      that a common host susceptibility is at work is not supported. Further
      investigations of seasonal influences are warranted.

PMID- 8756819
TI  - Impairment of central motor conduction to the diaphragm in stroke.
AB  - Respiratory complications are common in patients with stroke, but the involvement
      of the diaphragm in this setting is not completely understood. The purpose of
      this study was to assess corticodiaphragmatic pathways in patients with vascular
      hemiplegia. Fifteen patients were studied, nine with a capsular type of
      hemiplegia. Seven age-matched subjects served as the control group, and eight
      healthy young volunteers were studied to validate the methods by comparison with
      the literature. Diaphragm electromyogram was recorded bilaterally, using surface
      electrodes. Abductor pollicis brevis electromyogram was also recorded. After
      having checked the integrity of peripheral conduction, corticofugal pathways were
      studied using cortical magnetic stimulation, a reproducible and patient
      independent stimulus. Left and right conduction times to the diaphragm were
      symmetrical in the control subjects, the young volunteers, and the six patients
      with hemiplegia but without capsular lesion (16.5 to 20.1 ms). Conversely, they
      were markedly asymmetrical in patients with capsular hemiplegia, diaphragm
      response on the plegic side being abolished or markedly delayed. Although the
      clinical impact of these findings remains to be determined, this study confirms
      that "central diaphragm paralysis" can be present in stroke. It also indicates
      that there is no bilateral motor representation of each hemidiaphragm.

PMID- 8756820
TI  - Skeletal muscle adaptation to endurance training in patients with chronic
      obstructive pulmonary disease.
AB  - The purpose of this study was to evaluate the physiologic responses to endurance
      training in patients with moderate to severe airflow obstruction by specifically
      looking at changes in skeletal muscle enzymatic activities. Eleven patients (age
      = 65 +/- 7 yr, mean +/- SD, FEV1 = 36 +/- 11% of predicted value, range = 24 to
      54%) were evaluated before and after an endurance training program. Each
      evaluation included a percutaneous biopsy of the vastus lateralis and a stepwise
      exercise test on an ergocycle up to his/her maximal capacity. VE, VO2, VcO2, and
      serial arterial lactic acid concentration were measured during the exercise test.
      The activity of two oxidative enzymes, citrate synthase (CS) and 3-hydroxyacyl
      CoA dehydrogenase (HADH), and of three glycolytic enzymes, lactate dehydrogenase,
      hexokinase, and phosphofructokinase was determined. The training consisted of 30
      min exercise sessions on a calibrated ergocycle, 3 times a week for 12 wk. The
      aerobic capacity was severely reduced at baseline (VO2max = 54 +/- 12% of
      predicted) and increased by 14% after training (p < 0.05). For an identical
      exercise workload, there was a significant reduction in VE (34.5 +/- 10.0 versus
      31.9 +/- 9.0 L/min, p < 0.05) and in arterial lactic acid concentration (3.4 +/-
      1.3 versus 2.8 +/- 0.9 mmol/L, p < 0.01) after training. The lactate threshold
      also increased after training (p < 0.01) while the activity of the three
      glycolytic enzymes was similar at the two evaluations. In contrast, the activity
      of CS and HADH increased significantly after training (22.3 +/- 3.5 versus 25.8
      +/- 3.8 mumol/min/g muscle for CS, p < 0.05, and 5.5 +/- 2.9 versus 7.7 +/- 2.5
      mumol/min/g for HADH, p < 0.01). A significant inverse relationship was found
      between the percent changes in the activity of CS and HADH, and the percent
      changes in arterial lactic acid during exercise (p = 0.01). We conclude that
      endurance training can reduce exercise-induced lactic acidosis and improve
      skeletal muscle oxidative capacity in patients with moderate to severe chronic
      obstructive pulmonary disease (COPD).

PMID- 8756821
TI  - Comparison of cervical magnetic and transcutaneous phrenic nerve stimulation
      before and after threshold loading.
AB  - Brief supramaximal stimulation of the phrenic nerves (twitch) is considered a
      promising technique to detect diaphragmatic fatigue in humans. However, the most
      commonly employed methodology (transcutaneous stimulation) is technically
      difficult. Cervical magnetic stimulation is a recently described technique that
      is potentially simpler and may obviate some of the problems inherent with
      transcutaneous stimulation. The purpose of this study was to determine the
      ability of cervical magnetic stimulation to evaluate diaphragmatic function.
      Accordingly, we measured transdiaphragmatic pressure (Pdi) during transcutaneous
      and cervical magnetic stimulation of the phrenic nerves before and after a
      potentially fatiguing task; inspiratory threshold loading to task failure. During
      threshold loading, subjects generated approximately 60% of their maximal
      esophageal pressure with each breath until they could no longer reach the target
      pressure. At least 10 twitches were obtained during both transcutaneous and
      magnetic stimulation before and 10, 30, 60, and 120 min after threshold loading.
      Control twitch Pdi was significantly larger during magnetic stimulation compared
      with transcutaneous stimulation: 39.3 +/- 3.0 (mean +/- SE) versus 27.4 +/- 2.3
      cm H2O, p < 0.0005. This increase in twitch Pdi was solely due to the esophageal
      component. Following threshold loading, a significant reduction in transcutaneous
      twitch Pdi was seen in only three of the 10 subjects. Mean transcutaneous twitch
      Pdi fell only slightly from 27.4 +/- 2.3 during control to 25.1 +/- 2.2 cm H2O at
      10 min after loading (p < 0.004). In contrast, magnetic twitch Pdi was
      significantly reduced in nine of the 10 subjects following threshold loading.
      Mean magnetic twitch Pdi fell from 39.3 +/- 3.0 during control to 31.1 +/- 3.0 cm
      H2O at 10 min after loading (p < 0.0001). The average fall in twitch Pdi post
      loading (expressed as a percentage of the control value) was significantly
      greater for magnetic stimulation compared with transcutaneous stimulation: 21.0
      +/- 3.1 versus 7.8 +/- 2.9%, p < 0.0001. In summary: (1) in the fresh state,
      twitch Pdi is larger with magnetic stimulation compared with transcutaneous
      stimulation, and (2) transcutaneous and cervical magnetic twitch Pdi are affected
      differently by threshold loading to task failure.

PMID- 8756822
TI  - Movement arousals and sleep-related disordered breathing in adults.
AB  - Sleep fragmentation (an increase in the number of short EEG arousals) is
      considered a major determinant of excessive daytime sleepiness but is seldom
      quantified in sleep studies, and reference values are scarce at best. We present
      data on the movement arousal index (MAI) in five groups of subjects: normals,
      simple snorers, patients with the sleep apnea-hypopnea syndrome (SAHS), and
      patients with sleep-related oxygen desaturations due to chronic obstructive
      pulmonary disease or neuromusculoskeletal disorders. In normal subjects, the MAI
      was 13 +/- 7 (mean +/- SD). MAI was distinctly increased in most patients with
      SAHS and was strongly correlated with the apnea-hypopnea index and loss of both
      slow wave and REM sleep. It was corrected to normal by nasal continuous positive
      airway pressure (CPAP). There was some overlap of MAI between SAHS patients and
      snorers, suggesting that a minority of nonapneic snorers may suffer from daytime
      sleepiness due to upper airway dysfunction. Sleep fragmentation is not a feature
      of sleep-related hypoventilation due to COPD or neuromusculoskeletal disorders,
      and an increase of the number of movement arousals (MA) is very suggestive of
      upper airway dysfunction and of potential success of CPAP. Quantification of
      sleep fragmentation is feasible and clinically useful; it should be included in
      the assessment of sleep-related breathing disorders.

PMID- 8756823
TI  - Synergism of alveolar endotoxin "priming" and intravascular exotoxin challenge in
      lung injury.
AB  - Both endotoxin (lipopolysaccharides of gram-negative bacteria; LPS) and bacterial
      exotoxins may induce pulmonary microcirculatory disturbances when infused into
      the lung vasculature, and synergism between these types of microbial challenge
      has recently been noted. We now asked whether a bronchoalveolar LPS load in
      perfused rabbit lungs alters the responsiveness to a subsequent intravascular
      challenge with Escherichia coli hemolysin (ECH). In control lungs (sham
      aerosolization) and lungs undergoing LPS nebulization (alveolar deposition of
      approximately 22 micrograms), normal pulmonary artery pressure (PAP), lung
      weight, and ventilation/perfusion (V/Q) matching were observed. Intravascular ECH
      (0.013 hemolytic units/ml buffer fluid) increased PAP by approximately 10 mm Hg
      and lung weight by approximately 4 g within 10 min, paralleled by V/Q mismatch
      and a shunt flow of approximately 15%. In lungs "primed" for 3 h by a preceding
      bronchoalveolar LPS deposition, the same ECH dose provoked a dramatic increase in
      PAP to 40 to 50 mm Hg, a weight gain of approximately 10 g, and shunt flow of
      60%. Both vasoconstrictor response and V/Q mismatch were completely suppressed by
      preadministration and "rescue" application of the thromboxane receptor antagonist
      BM13.505. We conclude that a bronchoalveolar endotoxin load, though effecting no
      changes in pulmonary function by itself and showing no spillover into the
      vascular compartment, primes the lungs for a manifold increased vascular response
      to a subsequently infused exotoxin. Enhanced thromboxane-mediated
      vasoconstriction, largely redistributing perfusate flow from normally ventilated
      to shunt areas, is suggested as the predominant underlying event.

PMID- 8756824
TI  - Leukocyte recruitment after local endobronchial allergen challenge in asthma.
      Relationship to procedure and to airway interleukin-8 release.
AB  - We have investigated the profile of cellular recruitment into asthmatic airways
      after allergen and saline exposure and its relationship to interleukin-8 (IL-8)
      release. Fiberoptic bronchoscopy was used to instill allergen into the middle
      lobe while the right upper lobe received a sham saline challenge. Bronchoalveolar
      lavage (BAL) of both sites was performed either 4 or 24 h later. Neutrophil
      numbers in BAL fluid obtained 4 and 24 h after challenge were 17 and 48 times
      higher than prechallenge numbers (p < or = 0.001), but there was no statistically
      significant difference between the numbers of neutrophils at the two sites. In
      contrast, eosinophil numbers were increased by 6- and 20-fold, respectively, at 4
      and 24 h at allergen-challenged as compared with saline-challenged sites (p <
      0.005 and p < 0.02, respectively). Baseline concentrations of IL-8 in BAL fluid
      were undetectable in most cases. Four hours after allergen or saline exposure,
      BAL fluid IL-8 concentrations were: median, 200 pg/ml; range, 20 to 750 pg/ml and
      median, 123 pg/ml; range, < 20 to 800 pg/ml, respectively. These declined to 23
      pg/ml (range, < 20 to 126 pg/ml) and 43 pg/ml (range < 20 to 130 pg/ml),
      respectively, 24 h after exposure. There was a significant correlation between
      neutrophil numbers and IL-8 concentrations 4 h after saline exposure. These
      findings indicate that neutrophil infiltration is a nonspecific response to the
      procedure of bronchoscopy and lavage, in contrast to eosinophil recruitment,
      which is an allergen-specific phenomenon, and it suggests that IL-8 release may
      be involved in neutrophil recruitment.

PMID- 8756826
TI  - Lung function in premature rabbits treated with recombinant human surfactant
      protein-C.
AB  - We report the activity of recombinant human surfactant apoprotein-C (rSP-C[Cys]2)
      and various phospholipids in a preterm rabbit model of respiratory distress
      syndrome (RDS). Mixtures of rSP-C(Cys)2 and certain phospholipids had similar
      activity (lung compliance and lung pressure-volume behavior) to rabbit surfactant
      in this model. The activity of rSP-C(Cys)2 was maximal at 1 mol% protein and
      varied significantly with the phospholipid composition. Chemically synthesized SP
      C had similar activity to rSP-C(Cys)2. Deletion of six amino-terminal residues
      did not affect function. Substitution of cysteines and cysteine6 with adjacent
      serines (rSP-C[Ser]2) by site-specific mutagenesis minimized aggregation of rSP-C
      but did not affect activity. Palmitoylation of cysteine5 and cysteine6 in rSP-C
      (rSP-C[C16]2) did not enhance the activity of rSP-C(Cys)2. We conclude that
      bacterial expression is a practical source of functional SP-C, and that
      nonacylated forms of SP-C may be useful adjuvants to phospholipids in the
      treatment of RDS and possibly other forms of acute lung injury.

PMID- 8756825
TI  - P21Waf1/Cip1/Sdi1 and p53 expression in association with DNA strand breaks in
      idiopathic pulmonary fibrosis.
AB  - The tumor suppressor p53 protein is a transcription factor that plays a central
      role in the cellular response to DNA damage, and it can cause either G1 arrest or
      apoptosis. Recently, it was shown to induce the tumor suppressor
      p21Waf1/Cip1/Sdi1 (p21), which inhibits cyclin-CDK complex kinase activity.
      Although the etiology of idiopathic pulmonary fibrosis (IPF) is still uncertain,
      it is postulated that IPF begins with an initial inflammatory lesion localized to
      the alveolus and progresses on to chronic inflammation with alveolitis. We
      examined whether p53 and p21 are upregulated in association with chronic DNA
      damage in the bronchial and alveolar epithelial cells in patients with IPF in an
      attempt to repair the injury. We performed in situ detection of DNA strand breaks
      or apoptosis (TUNEL) in the tissues as well as immunohistochemistry (IHC) for p53
      and p21. Positive signals by TUNEL were detected mainly in the bronchiolar and
      alveolar epithelial cells in 10 of 14 lung specimens from patients with IPF. On
      the other hand, no positive signal by TUNEL was detected in normal lung
      parenchyma or in specimens of pulmonary emphysema. The IHC demonstrated that p53
      and p21 were expressed especially in hyperplastic bronchial and alveolar
      epithelial cells of lung tissues from all patients with IPF, except five
      specimens for p21. These results are consistent with those obtained by TUNEL. In
      normal lung parenchyma and specimens of pulmonary emphysema, p53 and p21 were not
      detected except in scattered alveolar macrophages and in the epithelial cells
      within localized fibrotic regions. These results suggest that p53 and p21 are
      upregulated in association with chronic DNA damage, resulting in either G1 arrest
      or apoptosis so that the DNA damage can be repaired in IPF. We speculate that
      chronic DNA damage and repair may lead to mutation of the p53 gene and
      tumorigenesis in IPF.

PMID- 8756827
TI  - Unilateral pulmonary artery thrombotic occlusion: is distal arteriopathy a
      consequence?
AB  - The characteristics and postoperative outcomes of a unique group of eleven
      patients with total unilateral pulmonary artery (PA) thromboembolic occlusion
      were compared with those of some 400 patients who underwent bilateral
      thromboendarterectomies during the same time period. Preoperative historical,
      physical, and laboratory features and postoperative outcomes of these two groups
      were analyzed. The unilateral group had no distinct historical features. However,
      they were younger (32 +/- 10 yr) than the bilateral group (51 +/- 15 yr),
      dominantly female (10 of 11) versus a male predominance (62%) in the bilateral
      group; had significantly lower preoperative PA mean pressures (30 +/- 12 versus
      46 +/- 12 mm Hg) and calculated pulmonary vascular resistance (360 +/- 293 versus
      901 +/- 467 dynes/s/cm-5); and small lung by chest radiograph was common (8 of
      11). Postoperatively, four unilateral patients developed unilateral rethrombosis
      (two immediate; two late, at several years postsurgery); this occurred in only
      one bilateral patient. Furthermore, of six patients with unilateral occlusion
      present more than 1 yr, reperfusion was poor in four despite an adequate
      thromboendarterectomy in all. Postoperative pulmonary angiograms in two of these
      disclosed apparent atrophy of central and distal pulmonary arteries. Prior animal
      investigation models indicate that unilateral PA occlusion is followed by
      development of a postobstructive arteriopathy in the resistance arteries of the
      occluded lung. The unusual outcomes in these 11 patients suggest that they may
      develop a similar arteriopathy which requires special management considerations
      at surgery and postoperatively.

PMID- 8756829
TI  - Intercellular adhesion molecule-1 mediates acid aspiration-induced lung injury.
AB  - Acid-aspiration-induced injury is one of the leading causes of adult respiratory
      distress syndrome. Intercellular adhesion molecule-1 (ICAM-1) is a ligand for
      lymphocyte-function-associated antigen-1 alpha (LFA-1 alpha), and it has been
      shown to be required for leukocyte migration into inflamed areas. The purpose of
      this report was to investigate the role of the ICAM-1/LFA-1 alpha pathway in a
      rat model of acid-aspiration-induced injury. Animals received 3.0 ml/kg HCI
      (0.1N; pH, 1.0) intratracheally pretreated with control monoclonal antibodies
      (mAbs) (HCI group) or anti-ICAM-1 and LFA-1 alpha mAbs (Test group). In the HCI
      group, increases in lung resistance (RL) (229 +/- 23% baseline), lung wet-to-dry
      weight ratio (W/D) (11.9 +/- 0.4), protein concentration (TP) (0.447 +/- 0.054
      mg/ml), and the number of neutrophils (PMN) (159.0 +/- 19.4 x 10(4)) of
      bronchoalveolar lavage fluid were observed. In the Test group, HCI-induced injury
      was significantly reduced (RL, 122 +/- 7% baseline; W/D, 7.2 +/- 0.1; TP, 0.277
      +/- 0.016 mg/ml; PMN, 8.8 +/- 0.8 x 10(4)). The administration of mAbs to ICAM-1
      and LFA-1 alpha after HCI instillation partially attenuated HCI-induced
      responses. These observations suggest that the ICAM-1/LFA-1 alpha pathway might
      be involved in the pathogenesis of adult respiratory distress syndrome caused by
      acid aspiration.

PMID- 8756828
TI  - Diffuse panbronchiolitis in the United States.
AB  - Diffuse panbronchiolitis (DPB), an important cause of progressive obstructive
      lung disease in the Far East, represents a distinctive sinobronchial syndrome
      with typical radiologic and histologic features. We have identified DPB in five
      citizens of the United States, three with histologic confirmation, who have never
      traveled to the Far East. There were four men and one woman, whose ages ranged
      from 46 to 75 yr at the time of diagnosis. All had a prior history of chronic
      sinusitis and presented with cough, dyspnea, and sputum production. Three were
      never smokers and two were current smokers. Pulmonary function testing revealed
      severe airflow limitation (the FEV1 ranging from 22% to 56% of predicted), and
      overdistention. All patients had high-resolution computed tomographic (HRCT)
      scans indicating centrilobular nodules with adjoining thickened and dilated
      bronchioles. In the three patients in whom open lung biopsy was performed, there
      was bronchiolocentric infiltration of lymphocytes, plasma cells, and foamy
      macrophages. Three patients remain alive and are being treated with chronic
      macrolide therapy. The clinical, radiographic, and histologic features of these
      patients closely resemble those described in Japanese patients. DPB must be
      considered in the differential diagnosis of sinopulmonary syndromes,
      bronchiolitis, and cryptic cases of obstructive lung disease among United States
      citizens, since therapy now offers an improved prognosis.

PMID- 8756830
TI  - Tenascin immunoreactivity as a prognostic marker in usual interstitial pneumonia.
AB  - In this investigation, tenascin (Tn) expression was studied in 51 cases of
      different types of fibrotic lung disorders originating for years 1981 to 1995.
      Our aim was to test if accumulation of Tn at the site of lung injury in usual
      interstitial pneumonia (UIP) could correlate with the prognosis. Lung biopsies
      taken from 28 patients with UIP, six with desquamative interstitial pneumonia
      (DIP), six with sarcoidosis, five with extrinsic allergic bronchioloalveolitis,
      five with bronchiolitis obliterans organizing pneumonia (BOOP), and one with
      nonspecific interstitial pneumonia were studied for the expression of Tn by using
      an immunohistochemical technique. In addition to Tn immunohistochemistry,
      selected cases were also studied by immunoelectron microscopy and Western
      blotting. For prognostic studies in UIP the clinical follow-up information was
      obtained from the patient records. The expression of Tn was increased in each
      type of fibrosis, especially in UIP. In immunoelectron microscopy the most
      prominent labeling in UIP was found in association with collagen fibers and
      within the type 2 pneumocytes. Every studied case of UIP showed reactivity for a
      polypeptide of M(r) approximately equal to 200,000 by Western blotting. In
      patients with UIP, increased Tn expression, especially under metaplastic
      bronchiolar-type epithelium, was associated with a shortened survival time.
      Immunoelectron microscopic findings support the idea that Tn in UIP is
      synthesized by the regenerating epithelial rather than interstitial cells in
      response to pulmonary interstitial inflammation.

PMID- 8756832
TI  - Nontuberculous mycobacteria in cystic fibrosis. An autopsy study.
AB  - We retrospectively studied lung and hilar lymph nodes at autopsy in 18 patients
      with cystic fibrosis (CF) who had antemortem sputum cultures positive for
      nontuberculous mycobacteria (NTM). Histologic features were compared with those
      of 18 patients with CF who had negative antemortem cultures. The most frequent
      species isolated was M. chelonae group (10 patients). Multiple cultures were
      positive for NTM in six patients. Three patients were clinically considered to be
      infected, and two received antimycobacteria drugs. Necrotizing pulmonary
      granulomas associated with granulomatous organizing pneumonia were found at
      autopsy in two patients, each of whom had multiple positive sputum cultures and
      clinical evidence of infection. In one of these, mycobacterial infection was
      considered to be an important factor in her terminal illness. Neither necrotizing
      granulomas nor granulomatous organizing pneumonia were seen in the lung tissue of
      patients whose antemortem cultures were negative for mycobacteria. There was no
      difference in the prevalence of other granuloma-like lesions between those with
      and those without positive sputum cultures. No mycobacteria-related granulomas
      occurred in hilar lymph nodes, although histoplasma granulomas involved hilar
      lymph nodes of three patients. We conclude that granulomatous mycobacterial lung
      disease is present in a minority of patients (two of six patients in this study)
      who have multiple positive cultures. Histologic evidence of infection was not
      found in patients who had only one of multiple sputum cultures positive for NTM.

PMID- 8756831
TI  - Lung cancer in patients with bullous disease.
AB  - There have been sporadic reports in the literature of an association between
      bullous disease of the lung and lung cancer; however, we believe that this
      clinical association is not well recognized. We present six cases in which
      bullous disease of the lung and lung cancer coexisted, and review the available
      literature on the topic. Five of the patients were males, the mean age of
      presentation was 42 yr (range: 32 to 62 yr), and all of the patients were
      smokers. Histologically the tumors in all six patients were non-small-cell
      carcinomas. The significantly younger age of these patients with lung cancer and
      bullous disease as compared with those reported in the literature with lung
      cancer but without bullous disease suggests that the association between these
      two processes is more than just coincidental. The utility of plain radiography
      and computerized tomography (CT) of the chest in screening patients with bullous
      disease for lung cancer is discussed.

PMID- 8756833
TI  - Salbutamol reduces pulmonary neutrophil sequestration of platelet-activating
      factor in humans.
AB  - To investigate whether salbutamol inhibits platelet-activating factor (PAF)
      induced neutrophil sequestration in the lungs, we studied eight nonatopic,
      nonsmoking, healthy subjects (six men; aged 27.0 +/- 1.5 (SE) yr) with PAF
      induced bronchial response. Prior to PAF challenge (24 micrograms), they inhaled
      either salbutamol (300 micrograms) or placebo in a randomized, double-blind,
      crossover manner two weeks apart. Respiratory system resistance (Rrs), arterial
      blood gases, and neutrophil counts were measured 4, 8, 12 and 30 min after PAF.
      Neutrophil kinetics in the lungs were assessed by tracking autologous 99mTc
      erythrocytes and 111in-neutrophils. Compared with salbutamol, arterial blood
      neutrophil counts fell (p < 0.04) maximally at 4 min after PAF, followed by a
      mild rebound neutrophilia, whereas Rrs increased (p < 0.01) and Pao2 decreased (p
      < 0.05) at 4 min only. The intrapulmonary activity of 111in-neutrophils after
      pretreatment with placebo was higher compared with salbutamol (1.98 +/- 0.15
      versus 1.33 +/- 0.23 cps/mCi/pixel) (p < 0.01) although both their initial
      sequestration (first-pass) and subsequent washout were not significantly
      different. Inhaled salbutamol blocks pulmonary neutrophil sequestration and lung
      function abnormalities following PAF challenge in humans.

PMID- 8756834
TI  - Arm span-height relationships in patients referred for spirometry.
AB  - Arm span has been proposed as a surrogate for standing height in the prediction
      of lung volumes in patients with thoracic deformities or who are unable to stand.
      The relationship between arm span and height has previously been reported as
      either a fixed ratio unaffected by age or as a regression equation in which the
      ratio varies as a function of age. We studied the relationship between standing
      height, arm span, race, sex, and age in 202 patients (ages 20 to 88 yrs) referred
      for screening spirometry. Multiple linear regression analysis found arm span,
      race, sex, and age to be predictive of standing height (r2 = 0.8659, p < 0.0001).
      Subgroup analysis revealed that age was a significant factor among males of
      either race, but not among females of either race. Fixed arm span to height
      ratios were also calculated for each group and may be used to estimate standing
      height with reasonable accuracy except at extremes of stature.

PMID- 8756835
TI  - The effect of lifestyle on wheeze, atopy, and bronchial hyperreactivity in Asian
      and white children.
AB  - There is increasing evidence linking Western culture to increasing prevalence of
      asthma. We have measured the prevalence of symptoms of asthma, bronchial
      hyperreactivity, and atopy in a sample of white and Asian inner city
      schoolchildren aged 8-11 yr in the U.K. and assessed the influence of certain
      aspects of western culture on these variables. Bronchial reactivity was measured
      by methacholine challenge, atopy by allergen skin prick tests, and symptoms of
      asthma and aspects of lifestyle by questionnaire. Degree of Westernization was
      assessed from dietary habit categorized as exclusively Asian, mostly Asian,
      mixed, or exclusively English. The questionnaire was completed by 92% of
      children. The 308 white and 539 Asian children were of similar age (mean 9.3 yr
      versus 9.4 yr) with slightly more girls in the Asian group (52.6% versus 47.4%).
      The white children reported more wheeze within the past year (14.2% versus 8.8%,
      p = 0.01) but less were atopic (29.5% versus 38.4%, p = 0.01) with no significant
      difference in the prevalence of hyperreactivity (31.5% versus 29.6%, p = 0.57).
      Most Asians (97%) included Asian food in their diet; 35% ate a mostly Asian diet,
      45% ate a mixed English and Asian diet, and 17% ate an exclusively Asian diet.
      After controlling for confounding factors whites were at higher risk of
      hyperreactivity and lower risk of atopy, and the risk of hyperreactivity and to a
      lesser extent atopy among Asian children was related to diet in a dose response
      fashion. The relative odds for hyperreactivity with an exclusively Asian, mostly
      Asian, or a mixed diet relative to an English diet were 0.31 (95% CI 0.15 to
      0.62), 0.88 (0.56 to 1.37), and 0.99 (0.65 to 1.49), and for atopy were 1.22
      (0.72 to 2.06), 1.47 (0.99 to 2.19), and 1.78 (1.23 to 2.58). These results
      suggest that diet or other closely related factors associated with Westernization
      are involved in the etiology of atopy and hyperreactivity.

PMID- 8756836
TI  - Unusual cause of lethal pulmonary aspergillosis in patients with chronic
      obstructive pulmonary disease.
AB  - Two patients admitted to two different medical wards of our institution following
      respiratory decompensation of chronic obstructive pulmonary disease (COPD) were
      subsequently transferred to the same room of the medical intensive care unit
      (ICU) and intubated. Both patients developed invasive pulmonary aspergillosis and
      died soon after. Because COPD itself is rarely associated with lethal pulmonary
      aspergillosis, both cases were reviewed, and a retrospective investigation was
      conducted. Both patients had repeated sputum cultures while on the medical ward
      before their admission to the ICU; none of the sample grew Aspergillus spp. A.
      fumigatus was found in tracheal aspirates of both patients from the first day of
      their intubation while in the ICU. The pulmonary condition of both patients
      worsened, and invasive aspergillosis was diagnosed by bronchoalveolar lavage.
      Despite therapy with amphotericin B, the patients died 16 and 22 d after
      intubation, respectively. Both deaths were attributed to pulmonary aspergillosis;
      autopsy confirmed a massive pneumonia of the five lobes due to A. fumigatus in
      one patient. Investigation revealed that an air filter had been replaced 30 h
      before the first patient was admitted to the room. Experimental air filter
      replacement performed 12 d after the second patient died revealed the presence of
      A. fumigatus on the surface of the filters as well as a 10-fold increase in room
      air fungal counts during the procedure. This study shows that exposure to high
      concentrations of airborne Aspergillus spp. related to air filter change was
      associated with fatal invasive aspergillosis in two mechanically ventilated
      patients. Such infection can be prevented by the establishment and application of
      guidelines for air filter replacement.

PMID- 8756837
TI  - Ileocolic resection for acute presentation of Crohn's disease of the ileum.
AB  - PURPOSE: Traditional therapy for patients with terminal ileitis found at
      laparotomy for appendicitis has been to perform appendectomy when the cecum is
      normal and to leave the diseased ileum in place. METHODS: To determine the role
      of ileocolic resection in the setting of acute ileitis, records of 1,421 patients
      with Crohn's disease seen from 1986 to 1994 were retrospectively reviewed.
      RESULTS: Crohn's disease was found at laparotomy for presumed appendicitis in 36
      patients (2.5 percent). Ten patients underwent ileocolic resection, 23 had
      appendectomy, and 3 had exploratory laparotomy alone. One patient whose appendix
      was removed also had ileocecal bypass. Of the 36 patients, 20 were women and 16
      were men. Mean age at operation was 24 (range, 11-61) years, and mean follow-up
      time was 14 (range, 0.1-49) years. After initial ileocolic resection, five
      patients (50 percent) required no further resection, with a mean follow-up time
      of 12.4 (range, 4-19) years. None required more than three ileocolic resections,
      with a mean follow-up time of 18.1 (range, 4-49) years. Of 26 patients treated
      traditionally, 24 (92 percent) required ileocolic resection for intractability or
      complications of Crohn's disease. Thirty-eight percent required resection within
      one year and 65 percent within three years (intractability, 8; obstruction, 3;
      fistula, 4; and perforation, 2). Of 24 patients who subsequently underwent
      resection, only 6 (25 percent) required further small-bowel resection for Crohn's
      disease, with a mean follow-up time of 13 (range, 0.1-34) years. CONCLUSION: The
      majority of patients found to have Crohn's disease at laparotomy for appendicitis
      required early ileocolic resection. Therefore, the traditional dictum of
      nonoperative therapy for these patients may not be in their best long-term
      interest and merits re-evaluation.

PMID- 8756838
TI  - Resection of liver metastases from colorectal cancer: are there any truly
      significant clinical prognosticators?
AB  - PURPOSE: This study was designed to evaluate the prognostic significance of
      various prognostic factors affecting recurrence after resection of colorectal
      hepatic metastases. PATIENTS AND METHODS: Records of 54 patients who had hepatic
      resection between 1986 and 1993 for metastatic liver tumor from colorectal cancer
      were reviewed. Factors analyzed were those reported to be of prognostic
      significance in other studies, including gender, primary tumor site, Dukes stage,
      diagnostic interval, grade, preoperative carcinoembryonic antigen (CEA) level,
      number of metastases, size of metastases, distribution of metastases, type of
      resection, resection margin, and estimated blood loss. RESULTS: Average follow-up
      of surviving patients was 28 (range, 12-89) months. Average survival time from
      date of hepatic resection was 26 months, with an estimated actuarial survival
      rate of 25.5 percent at five years. Using the multivariate analysis of factors,
      gender and preoperative CEA level were shown to be significantly related to
      overall survival (P = 0.0455 and 0.054, respectively). Cancer of the right side
      colon had significant correlation with hepatic "recurrence" (P = 0.0071).
      CONCLUSIONS: Female patients and those with peroperative CEA values higher than
      20 ng/ml have a better chance of survival following hepatic resection. Cancer of
      the right colon has a greater tendency for hepatic recurrence than that of the
      left colon.

PMID- 8756839
TI  - Long-term effect of vaginal deliveries on anorectal function in normal
      perimenopausal women.
AB  - PURPOSE: This study was undertaken to determine the long-term effects of vaginal
      deliveries on anorectal function in healthy perimenopausal women. METHODS: An
      observational study of 144 perimenopausal women living in the county of Aarhus,
      Denmark, aged 45 to 57 (mean, 50) years were randomly selected from the National
      Register. All women had delivered 0 to 6 (mean, 2) times 10 to 34 years before
      the investigation. Examinations describing pelvic floor function were
      measurements of perineal position at rest and descent during straining, anal
      mucosa electrosensitivity, maximum resting pressure and maximum squeeze pressure
      of the anal sphincters, and pudendal nerve terminal motor latency. All tests were
      performed by one of the authors (AMR) and without knowledge of parity. Data were
      analyzed using the multiple regression technique, and all associations between
      anorectal function and parity were corrected for age and hysterectomy status.
      RESULTS: Increasing parity correlated with a lowered perineal position at rest
      (correlation coefficient (r) = 0.26; P = 0.003), an increased descent during
      straining (r = 0.24; P = 0.006), an increased threshold of anal mucosa
      electrosensitivity (r = 0.22, P = 0.008), and an increased pudendal nerve
      terminal motor latency on both sides (r = 0.27; P = 0.002). No effect of parity
      of the maximum resting pressure (r = 0.06; P = 0.70) and maximum squeeze pressure
      (r = 0.06; P = 0.36) was found. The number of vaginal deliveries account for only
      a minor fraction of the total variability seen in the tests of pelvic floor
      function (between 1.6 and 5.7 percent). CONCLUSION: Repeated vaginal deliveries
      have a long-term adverse effect on anorectal physiology in a population of
      randomly selected healthy perimenopausal women.

PMID- 8756840
TI  - Investigation of fecal incontinence with endoanal ultrasound.
AB  - PURPOSE: This study was undertaken to audit the results of endoanal ultrasound in
      patients with fecal incontinence. METHODS: Endoanal ultrasound was used to
      investigate 53 patients with fecal incontinence. Data for endoanal ultrasound
      were collected prospectively. Results were compared with clinical and obstetric
      history, obtained retrospectively from case notes, and were compared with
      manometric and operative findings. RESULTS: Sphincter abnormalities were
      identified in 42 of 53 patients. A total of 28 anterior defects were thought to
      be obstetric in origin. Fourteen other defects were secondary to anal pathology
      or surgery. Patients with anterior external sphincter defects either had complete
      defects (4 patients; mean age, 31 years) or proximal defects (24 patients; mean
      age, 55 years). For patients with a proximal defect, 38 percent gave a history of
      obstetric tear, episiotomy, or forceps delivery, and the rest declared having had
      an apparently normal delivery. Only 50 percent had a sphincter weakness that was
      evident on clinical examination. Of those studied with manometry, only 21 percent
      had low squeeze pressures consistent with an external sphincter defect.
      CONCLUSIONS: Sphincter defects seen on ultrasound may not have a history of
      obstetric trauma or abnormal clinical and manometric findings. Endoanal
      ultrasound is recommended in all patients with fecal incontinence to detect
      occult sphincter defects.

PMID- 8756841
TI  - Basal and meal-stimulated colonic absorption.
AB  - PURPOSE: Few quantitative experiments evaluating colonic absorption of water and
      electrolytes have been performed using an awake, conscious animal model. The
      purpose of these experiments was to develop this type of model and evaluate both
      basal and meal-stimulated colonic absorption of water and electrolytes. METHODS:
      Canine Thiry-Vella fistulas were created using a 20 cm segment of distal colon
      under general anesthesia. Colonic absorption studies were performed using
      infusion of the Thirty-Vella fistulas with a buffer solution containing
      [14C]polyethylene glycol. Electrolyte analysis and concentration of radioactivity
      in the effluent were obtained and used to calculate the net flux of water,
      sodium, and chloride. Each study consisted of an one-hour basal period and a
      three-hour experimental period divided into two groups. Group 1 received no meal.
      Group 2 orally ingested a mixed meal at the completion of the basal hour.
      RESULTS: In the basal state, water and electrolytes are absorbed from the distal
      colon at a steady and constant rate. An orally ingested meal produces a
      statistically significant increase in the rate of absorption, independent of
      direct colonic luminal contact with the nutrients of the meal given. CONCLUSIONS:
      These studies demonstrate an in vivo quantitative and qualitative measure of
      mammalian colonic water and electrolyte absorption. An increase in absorption
      rate occurs in response to a meal that is probably the result of an unidentified
      neural or humoral signal.

PMID- 8756842
TI  - Selective preservation of the anal transition zone in ileoanal pouch procedures.
AB  - PURPOSE: A prospective trial was conducted to evaluate use of certain
      preoperative criteria in the choice of operative technique for ileal pouch-anal
      anastomosis (IPAA). Handsewn vs. stapled anastomotic techniques were compared as
      was preservation vs. excision of the anal transition zone (ATZ). METHODS: Over an
      18-month period, 40 consecutive patients underwent restorative proctocolectomy
      with IPAA for ulcerative colitis (31 cases) or familial adenomatous polyposis (9
      cases). In 28 patients, ATZ was completely excised, by either a transanal
      mucosectomy with handsewn anastomosis (Group I, 13 cases) or by double-stapled
      technique (Group II, 15 cases). The ATZ was preserved and the anastomosis was
      double-stapled in colitis patients with suboptimum sphincter function and/or
      greater than 50 years of age in the absence of dysplasia or severe distal
      proctitis (Group III, 12 cases). RESULTS: Groups I and II patients were
      homogeneous in their preoperative variables and had equivalent functional
      outcome. Group III patients were older (P = 0.0001), with weaker preoperative
      anal sphincter resting tone (P = 0.024). Compared with Groups I and II, patients
      in Group III had significantly greater 24-hour stool frequency (P = 0.0056),
      daytime stool frequency (P = 0.0125), and incidence of daytime fecal seepage (P =
      0.007). There was no significant difference in other outcome variables in Group
      III patients. There was no difference in morbidity in the three groups.
      CONCLUSIONS: Transanal mucosectomy with handsewn anastomosis provided early
      functional results equivalent to low anal transection with double-stapled IPAA in
      younger patients with excellent preoperative sphincter function. A double-stapled
      technique with preservation of the ATZ may be reserved for older patients, with
      poorer anal sphincter function, at minimum dysplasia/cancer risk, to optimize
      continence figures.

PMID- 8756843
TI  - Anal sphincter repair improves anorectal function and endosonographic image. A
      prospective clinical study.
AB  - PURPOSE: This study investigated the effect of anal sphincter repair on fecal
      continence in relation to anal endosonography and anal manometry. METHODS:
      Eighteen patients (7 male, 11 female) with anal sphincter defects and complaints
      of fecal incontinence (5), soiling ( = liquid discharge; 3), or both (10) were
      studied before and after sphincter repair with endosonography and anal manometry.
      Complaints were the result of obstetric trauma (7), surgical trauma (7), both
      (3), and other trauma (1). Five patients had previous surgery. Preoperative
      endosonography showed a defect of both sphincters in nine patients, a defect of
      the external anal sphincter in five patients, and a defect of the internal anal
      sphincter in four patients. An overlapping sphincter repair was performed.
      RESULTS: Postoperatively and subjectively (S; patient's view), 13 (72 percent)
      patients became continent or improved; in 5 (28 percent) patients the complaints
      were unaltered. Objectively (O) (incontinence or soiling frequency), these
      figures were 12 (67 percent) and 6 (33 percent). Postoperative endosonographic
      images improved in 14 (78 percent) patients; defects of the sphincters (almost)
      disappeared (4) or were smaller (10). In the other four patients, images were
      unchanged. In two patients, overlapping of the muscle was clearly visible with
      anal endosonography. Clinical result (subjective (S) and objective (O)) of
      sphincter repair correlated with changes in anal endosonography (S, r = 0.64, P <
      0.004; O, r = 0.51, P = 0.03) and anal manometry (S, r = 0.54, P = 0.038; O, r =
      0.44, P = 0.09 (not significant)) and not with pudendal nerve latency.
      CONCLUSIONS: In 78 percent of our patients, endosonographic sphincter defect had
      diminished or disappeared after sphincter repair. There was a good correlation
      between clinical effect of sphincter repair and changes with anal endosonography
      and anal manometry. Postoperative persistent incontinence is attributable to
      remaining sphincter defects. Anal endosonography should be performed as a routine
      procedure in patients with fecal incontinence or soiling, also after failed
      surgery.

PMID- 8756844
TI  - Local therapy of rectal tumors.
AB  - PURPOSE: The aim of the study is to outline the rising importance of local
      treatment of rectal tumors and a changing strategy in therapy of early rectal
      cancer. METHODS: As the surgical procedure, transanal endoscopic microsurgery was
      used. Indications for the local procedure were pT1 low-risk tumors and tumors of
      higher stages in patients with severe risk factors and of those who refused the
      operation according to oncologic guidelines. RESULTS: A total of 236 rectal
      adenomas and 98 carcinomas were locally excised using the transanal endoscopic
      microsurgery technique. Mortality rate was 0.3 percent, and rate of complications
      requiring surgical reintervention was 5.5 percent in adenomas and 8 percent in
      carcinomas. Final histology of removed carcinomas revealed 56 pT1, 27 pT2, and 15
      pT3 stages. After an average follow-up time of 24 months, two recurrences were
      observed in the group of patients with pT1 low-risk carcinomas who only underwent
      local therapy. In both cases, a second intervention for cure was undertaken but
      for tumors in a late stage. CONCLUSIONS: In selected cases, local therapy of
      rectal carcinoma avoids high morbidity and mortality of the classical operation.
      Quality of life will be improved, especially if an artificial anus can be
      avoided. In case of recurrence, the chance of a secondary procedure for cure is
      not to be underestimated.

PMID- 8756845
TI  - Long-term results of ileal pouch-anal anastomosis in patients with Crohn's
      disease.
AB  - PURPOSE: Ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice
      for most patients with chronic ulcerative colitis. Crohn's disease is, however, a
      contraindication. Because distinction between UC and Crohn's disease can be
      difficult, some patients with Crohn's disease inadvertently undergo IPAA. The aim
      of this study was to determine the long-term outcome of patients with Crohn's
      disease who have undergone IPAA. METHODS: A total of 37 patients (20 men) were
      studied. Each had undergone mucosectomy with handsewn IPAA (J-pouch, n = 35; S
      pouch, n = 1; W-pouch, n = 1). Histologic examination of the resected specimen at
      time of IPAA showed features of ulcerative colitiis (n = 22), indeterminate
      colitis (n = 9), or Crohn's disease (n = 6). The stoma was closed in all
      patients. RESULTS: A total of 11 of 37 patients developed complex fistulas (pouch
      cutaneous (n = 6), pouch-vaginal (n = 4), or pouch-vesical (n = 1). Crohn's
      disease has recurred in the pouch (n = 20), anal canal (n = 4), pouch and anal
      canal (n = 10), and elsewhere (n = 3). After ten years (range, 3-14), the pouch
      remains in situ in 20 patients in whom frequency of bowel movement is seven times
      (3-10)/24 hours, in situ but defunctioned in seven patients, and excised in ten
      patients (failure rate, 45 percent). CONCLUSIONS: Inadvertent IPAA for Crohn's
      disease is associated with a high rate of failure (45 percent) but an acceptable
      long-term functional result if the pouch can be kept in situ.

PMID- 8756846
TI  - Defecography and proctography. Results of 744 patients.
AB  - PURPOSE: Radiographic imaging of dynamic changes within the pelvic cavity and
      rectum during evacuation has been recognized as a valuable method of assessment.
      This study was designed to assess the incidence and clinical significance of
      defecographic findings in patients with possible evacuation disorders. MATERIALS
      AND METHODS: All defecographic studies were reviewed by a single colorectal
      surgeon familiar with patients' histories and physical findings. RESULTS: Between
      July 1988 and July 1995, 744 patients (566 females and 178 males) with a mean age
      of 63.5 (range, 12-95) years had defecographic and proctographic examination.
      Four hundred forty-six (60 percent) patients were diagnosed who complained of
      constipation, 123 (16.5 percent) of fecal incontinence, 42 (5.6 percent) of
      rectal prolapse, 82 (11 percent) of rectal pain, and 51 (6.9 percent) had a
      combination of more than one of these diagnoses. Although 93 (12.5 percent) of
      these evaluations were considered normal, 61 (8 percent) revealed rectal
      prolapse, 191 (25.7 percent) rectocele, 82 (11 percent) sigmoidocele, and 94
      (12.6 percent) intussusception; in 223 (30 percent) patients, a combination of
      these findings was noted. Patients with paradoxical puborectalis contraction had
      an extremely high frequency of constipation compared with other symptoms (P <
      0.0001). CONCLUSIONS: Defecography can reveal abnormalities in the majority of
      patients with evacuatory disorders. There was a high incidence of rectocele,
      sigmoidocele, and intussusception. Care must be taken not to treat patients
      strictly based on radiographic findings.

PMID- 8756847
TI  - Right colonic arterial anatomy. Implications for laparoscopic surgery.
AB  - PURPOSE: Hemorrhagic complications can be a major cause of conversion and/or
      morbidity during laparoscopic intestinal surgery. The limited exposure currently
      provided in laparoscopic intestinal resection demands a precise knowledge of
      mesenteric vascular anatomy to avoid such complications and to expedite the
      procedure. Most surgical texts depict a "normal pattern" of arterial supply to
      the right colon consisting of three arterial branches (ileocolic artery, right
      colic artery, and middle colic artery) arising independently from the superior
      mesenteric artery (SMA). Based on previous reports and clinical observations, we
      hypothesized that the right colic artery arises infrequently from the SMA, and
      most commonly, there are only two colonic arteries arising independently from the
      SMA. METHODS: We performed detailed dissections of the SMA in 56 human cadavers.
      RESULTS: We found the ileocolic artery in all of our cases and the middle colic
      artery in 55 of 56 cadavers but only six cases of a right colic artery emanating
      directly from SMA. CONCLUSIONS: Our data, combined with review of published
      anatomic studies, lead us to conclude that in the vast majority of cases there
      are only two independent branches arising from SMA that supply the large
      intestine, the ileocolic and the middle colic arteries. The right colic artery
      directly arising from SMA is unusual (10.7 percent). This knowledge may help
      lower the risk of vascular complications during laparoscopic intestinal surgery.

PMID- 8756848
TI  - Dynamic graciloplasty. Complications and management.
AB  - PURPOSE: Patients with intractable fecal incontinence, in whom all other
      treatment failed, can be treated by dynamic graciloplasty. Good results have been
      reported, but this technique involves specific problems. All problems that
      occurred over an eight-year period are presented, and management is discussed.
      METHODS: Dynamic graciloplasty was performed in 67 patients with a mean follow-up
      of 2.7 years. All patients were monitored by physical examination, anal
      manometry, defecography, and electromyography at fixed intervals. All
      complications were noted and treated. Continence was defined as being continent
      to solid and liquid stools. RESULTS: The technique was successful in 52 patients
      (78 percent), whereas failures occurred in 15 patients (22 percent).
      Complications resulted from technical problems, problems with infection, and
      problems attributable to an abnormal physiology of the muscle or an anorectal
      functional imbalance. In total, 53 complications were identified in 36 patients.
      Most technical problems, concerning the transposition and stimulation of the
      gracilis muscle, could be treated. Failures were attributable to a bad
      contraction of the distal part of the muscle (n = 4) and perforation of the anal
      canal during stimulation (n = 1). In eight patients, infection of the stimulator
      and leads required explantation. Three patients did not regain continence after
      reimplantation. Apart from moderate constipation, physiologic complications were
      very hard to treat and resulted in failures in five patients because of overflow
      incontinence, soiling, a nondistending rectum, strong peristalsis, and strong
      constipation. In two patients, the technique failed despite a well-contracting
      graciloplasty; no clear reason for the failure was found. CONCLUSION:
      Complications associated with the technique of dynamic graciloplasty such as loss
      of contraction, infection, bad contraction in the distal part of the muscle, and
      constipation can often be prevented or treated. Difficulties related to an
      impaired sensation and/or motility, attributable to a congenital cause or
      degeneration, are impossible to treat, and this signifies that a good selection
      of patients is essential to prevent disappointment.

PMID- 8756849
TI  - Factors influencing recurrence in Crohn's disease. An analysis of a consecutive
      series of 353 patients treated with primary surgery.
AB  - PURPOSE: This study was undertaken to investigate the factors that influenced the
      risk of symptomatic recurrence in patients with Crohn's disease who were treated
      with primary resective surgery. METHODS: Data regarding age, gender, time from
      diagnosis to surgery, medication, preoperative infectious complications,
      laboratory values, emergency/elective surgery, location and extent of disease,
      and resection margins were analyzed in relation to recurrence in 353 patients who
      were undergoing a "curative" resection in 1969 to 1986. RESULTS: Univariate
      analyses showed a higher risk of recurrence in women with ileal and ileocolonic
      disease than in men (P < 0.05), in patients with ileocolonic disease compared
      with those with isolated ileal disease (P < 0.05), and in ileal disease patients
      with an increased disease extent (P < 0.05). In a multivariate analysis performed
      on patients with ileal disease, increased disease extent, limited resection on
      the colonic side, and referral from other hospitals were three independent
      variables that indicated an increased risk of recurrence (P < 0.05). Length of
      disease-free resection margins did not influence the risk of recurrence either in
      univariate or in multivariate analysis (P > 0.05). CONCLUSIONS: Disease extent
      has prognostic value regarding the risk of symptomatic recurrence in Crohn's
      disease, whereas the length of resection margins does not influence the risk of
      relapse. These results favor a conservative approach, particularly in patients
      with extensive disease.

PMID- 8756850
TI  - High resolution magnetic resonance imaging of the anal sphincter using a
      dedicated endoanal coil. Comparison of magnetic resonance imaging with surgical
      findings.
AB  - PURPOSE: To obtain high resolution images of the anal sphincter and adjacent
      anorectum using an endoanal coil in patients with sepsis, trauma, and low rectal
      tumors and to compare imaging appearances with findings at time of surgery.
      PATIENTS AND METHODS: A cylindrical saddle geometry coil (diameter, 9 mm; length,
      75 mm) was used to examine 30 patients (mean age, 53.6 years). Pathologies
      included perianal sepsis (10 patients), obstetric trauma (7 patients), and low
      rectal tumors (13 patients). Imaging was performed on an 0.5-T Picker Asset or
      1.0-T Picker HPQ Vista (Picker International, Highland Heights, OH). T1 and T2
      weighted and short inversion time inversion recovery transverse images and T1
      weighted coronal images were obtained. Intravenous gadopentetate dimeglumine (0.1
      mmol/kg) was given to all patients with suspected infection and neoplasms.
      RESULTS: Abscesses and fistulas identified using magnetic resonance imaging (MRI)
      in patients with perianal sepsis were confirmed at surgery in all cases; site of
      fistulous internal opening into the anal canal was correctly identified in 80
      percent of cases. Extent of sphincter tear was correctly assessed on endoanal MRI
      in all patients with obstetric trauma when compared with surgical findings. Tumor
      invasion of anal sphincter was seen in 38.5 percent of low rectal carcinomas.
      CONCLUSIONS: MRI with an endoanal coil provides detailed images of the site and
      extent of anal fistulas, sphincter tears, and local tumors and is of considerable
      value in preoperative assessment.

PMID- 8756851
TI  - Nonsurgical removal of a rectal foreign body using a vacuum extractor. Report of
      a case.
AB  - PURPOSE: Rectal foreign bodies can be extracted by nonsurgical methods. However,
      glass objects require technical considerations to minimize morbidity and may
      necessitate surgical extraction. We describe a technique that allowed safe
      transanal extraction of a glass foreign body and avoided laparotomy. METHODS: A
      patient with a history of a previous rectal foreign body that required laparotomy
      presented with another incarcerated rectal foreign body. After attempts at manual
      extraction failed, spinal anesthesia was induced, and an obstetric vacuum
      extractor was used to transanally withdraw the glass foreign body. RESULTS: The
      glass foreign body was withdrawn uneventfully using the vacuum extractor.
      Laparotomy was avoided. The patient was hospitalized for observation and
      discharged 24 hours later. CONCLUSIONS: Use of the delivery vacuum extractor
      provided a safe, cost-effective method of glass foreign body removal by the
      transanal route. Literature review found no other reports of rectal foreign body
      removal by this method.

PMID- 8756852
TI  - Carcinoid tumor: an extremely unusual presacral lesion. Report of a case.
AB  - PURPOSE: Use of endorectal ultrasonography in preoperative evaluation of a
      presacral lesion is demonstrated. METHOD: The natural history, presentation,
      evaluation, and treatment of presacral lesions in adult patients are presented.
      The case of a female patient with a presacral carcinoid tumor is presented and
      discussed. RESULTS: The patient underwent preoperative evaluation including
      physical examination, hematologic studies, proctosigmoidoscopy, magnetic
      resonance imaging, computed tomographic scanning, and endorectal ultrasonography.
      Ultrasonography proved to be extremely valuable in differentiating tumor
      compression from tumor invasion of the rectal wall. The patient underwent en bloc
      excision of the lesion, surrounding tissue, and coccyx. Pathologic diagnosis was
      carcinoid tumor, possibly replacing a presacral lymph node. Postoperative
      complete gastrointestinal tract work-up and urinary 5-hydroxyindoleacetic acid
      analysis along with preoperative imaging revealed no evidence of synchronous
      lesions or additional metastases. CONCLUSIONS: Presacral lesions are extremely
      rare entities. The role of endorectal ultrasonography has not been clearly
      defined. This case demonstrates the value of this simple and safe imaging
      procedure in detecting bowel wall compression vs. invasion, greatly assisting in
      planning an operative approach.

PMID- 8756853
TI  - Constipation after dynamic graciloplasty.

PMID- 8756854
TI  - Life-threatening lower intestinal bleeding leading to discovery of a colonic
      paraganglioma.

PMID- 8756855
TI  - Raging wildfire in Alaska forces evacuation of homes, displaces companion
      animals.

PMID- 8756856
TI  - More letters on article about nonhuman animal research.

PMID- 8756857
TI  - More letters on article about nonhuman animal research.

PMID- 8756859
TI  - Final action on sexual discrimination case.

PMID- 8756858
TI  - More letters on article about nonhuman animal research.

PMID- 8756860
TI  - Praise for Army laboratory animal training program.

PMID- 8756861
TI  - Pre-harvest food safety as part of a farm-to-table pathogen reduction program to
      prevent foodborne disease.

PMID- 8756862
TI  - Believes women are better at raising calves.

PMID- 8756863
TI  - Endorses concept of pet insurance.

PMID- 8756864
TI  - Giant hogweed photodermatitis in two dogs in Bellevue, Washington.

PMID- 8756865
TI  - A salute to dairy practitioners.

PMID- 8756866
TI  - Effective communication with older clients.

PMID- 8756867
TI  - What is your diagnosis? Faint vertical condylar radiolucency, secondary to
      incomplete ossification of the humeral condyle.

PMID- 8756868
TI  - What is your diagnosis? Oblique fracture of the right hind distal phalanx in a
      horse.

PMID- 8756869
TI  - Theriogenology question of the month. Histologic examination of ovarian tissue to
      confirm the diagnosis of a granulosa cell tumor.

PMID- 8756870
TI  - Molecular techniques in the diagnosis and control of paratuberculosis in cattle.

PMID- 8756871
TI  - Factors associated with the decision to surrender a pet to an animal shelter.

PMID- 8756872
TI  - An economic perspective on the symposium "Managing your economic future in
      veterinary medicine".

PMID- 8756873
TI  - Usefulness and limitations of three serologic methods for diagnosing or excluding
      chlamydiosis in birds.
AB  - Diagnostic serology by use of elementary body agglutination is the most useful
      serologic method for diagnosis of chlamydiosis in birds, because it detects only
      IgM activity. A titer of 10 in budgerigars, cockatiels, and lovebirds and of > or
      = 20 in other types of birds is interpreted as being indicative of current
      infection. Latex agglutination, with detects IgM and IgG activity, may be useful
      in detecting large changes in titer. Direct complement fixation, detecting only
      IgG activity, is usable to detect past infection whenever elementary body
      agglutination and latex agglutination titers are < 10. Limitations of serologic
      results necessitating additional confirmatory testing are lack of titers in the
      acute phase of disease and diagnostic titers in clinically normal birds with low
      grade chronic infections and in birds with prolonged maintenance of titers.
      Additional suggested examinations are chlamydial culture by use of
      choanal/oropharyngeal swab samples, WBC count, determination of hepatic
      associated enzyme activity, chlamydial ELISA by use of the aforementioned swab
      samples, and additional serologic testing.

PMID- 8756874
TI  - Economics of feeding pasteurized colostrum and pasteurized waste milk to dairy
      calves.
AB  - OBJECTIVE: To estimate the marginal contribution of pasteurization of waste milk
      and colostrum to gross margin per calf at weaning and to estimate the minimum
      number of cattle on a dairy farm for pasteurization to be profitable. DESIGN:
      Randomized, controlled, clinical trial. ANIMALS: 300 Holstein calves. PROCEDURE:
      The performance of calves fed pasteurized colostrum and waste milk was compared
      with the performance of calves fed nonpasteurized colostrum and waste milk.
      Costs, revenues, and gross margins for the 2 groups were compared. RESULTS:
      Calves fed pasteurized colostrum and waste milk were worth an extra $8.13 in
      gross margin/calf, compared with calves fed nonpasteurized colostrum and waste
      milk. The minimum number of cattle for which feeding pasteurized colostrum and
      waste milk was calculated to be economically feasible was 315 calves/d (1,260-cow
      dairy farm). CLINICAL IMPLICATIONS: An economic benefit was associated with
      feeding pasteurized colostrum and waste milk. Additional benefits that may accrue
      include higher mean weight gain and lower mortality rate of calves as well as
      calves that have fewer days in which they are affected with diarrhea and
      pneumonia.

PMID- 8756875
TI  - Factors that impede animal movement at slaughter plants.
AB  - Factors that impede animal movement in slaughter plants and that are likely to
      cause excitement, stress, or bruises are major mistakes in the design of chutes
      and stockyard pens; lack of training or poor supervision of employees;
      distractions that impede animal movement, such as sparkling reflections on a wet
      floor, air hissing, high-pitched noise, or air drafts blowing down the chute
      toward approaching animals; poor maintenance of facilities, such as worn out or
      slick floors that cause animals to fall; and animals from genetic lines that have
      an excitable temperament. Veterinarians need to be aware of these factors because
      such factors can cause animals to balk and become excited, which may result in
      excessive prodding. When a handling system is being evaluated, one must be
      careful to discriminate between a major design mistake and small distractions
      that can be easily corrected, but that can ruin the performance of the best
      systems. A survey of 29 Canadian slaughter plants revealed that 21% (6 plants)
      had slick floors that would cause animals to slip and fall, and 27% (8 plants)
      had high-pitched motor noise or hissing air that caused animals to balk. Air
      drafts blowing down the chutes, which will often impede animal movement, were a
      problem in 10% (3) of the plants. Simple modifications of lighting and
      elimination of air drafts and hissing will often greatly improve animal movement.

PMID- 8756876
TI  - Use of immunohistochemistry and polymerase chain reaction for detection of
      oncornaviruses in formalin-fixed, paraffin-embedded fibrosarcomas from cats.
AB  - OBJECTIVE: To determine whether there was intralesional infection or expression
      of FeLV or feline sarcoma virus in suspected vaccine-associated fibrosarcomas in
      cats. DESIGN: Prospective case series. SAMPLE POPULATION: 130 suspected vaccine
      associated fibrosarcomas from cats and 1 multicentric fibrosarcoma from 1 cat.
      PROCEDURE: Excisional biopsy specimens were fixed in formalin and embedded in
      paraffin. Expression of FeLV antigen was assessed, using a polyclonal goat anti
      FeLV glycoprotein 70 (gp 70) serum and an avidinbiotin immunoperoxidase staining
      technique. The FeLV genome was detected with a polymerase chain reaction (PCR),
      using primers targeted to a conserved sequence in the untranslated region of the
      long terminal repeat (LTR) of the FeLV. RESULTS: FeLV gp 70 and LTR sequence were
      detected in a multicentric fibrosarcoma. All 130 of the suspected vaccine
      associated fibrosarcomas were FeLV gp 70 negative on the basis of
      immunohistochemical test results: 100 fibrosarcomas also were examined by use of
      PCR and were negative for FeLV LTR region. CLINICAL IMPLICATIONS: Exogenous
      retroviruses, FeLV, and feline sarcoma virus were not detected in these suspected
      vaccine-associated fibrosarcomas, using immunohistochemistry and PCR. Additional
      testing will be required to determine the nature of genomic alterations that are
      involved in the oncogenesis of vaccine-associated fibrosarcomas in cats.

PMID- 8756877
TI  - Use of low- and high-dose dexamethasone tests for distinguishing pituitary
      dependent from adrenal tumor hyperadrenocorticism in dogs.
AB  - OBJECTIVE: To evaluate low- and high-dose dexamethasone suppression tests for
      differentiating pituitary dependent hyperadrenocorticism (PDH) from adrenal tumor
      hyperadrenocorticism (ATH) in dogs. DESIGN: Prospective study. ANIMALS: 181 dogs
      with PDH and 35 dogs with ATH. PROCEDURE: Plasma cortisol concentrations from
      dogs with naturally developing hyperadrenocorticism were evaluated before, and 4
      and 8 hours after administration of standard low- and high-doses of dexamethasone
      (0.01 mg/kg of body weight, i.v., and 0.1 mg/kg, i.v.; respectively). RESULTS: In
      response to the low-dose test, all but 3 dogs had an 8-hours post-dexamethasone
      plasma cortisol concentration that was consistent with a diagnosis of
      hyperadrenocorticism, that is, > or = 1.4 micrograms/dl. Criteria used to
      distinguish PDH from ATH in response to low-dose dexamethasone included a 4-hour
      post-dexamethasone plasma cortisol concentration < 50% of the basal value or <
      1.4 micrograms/dl, or an 8-hours post-dexamethasone plasma cortisol concentration
      < 50% of the basal concentration. Criteria used to distinguish PDH from ATH in
      response to high-dose dexamethasone included 4- or 8-hour post-dexamethasone
      plasma cortisol concentrations < 50% of the basal concentration or < 1.4
      micrograms/dl. In response to the low-dose test, 111 dogs met criteria for
      suppression (each had PDH). In response to the high-dose test, 137 dogs met
      criteria for suppression (2 had ATH, 135 had PDH). Twenty-six dogs with PDH (12%)
      had indications of adrenal suppression in response to high-dose but not low-dose
      testing. CLINICAL IMPLICATIONS: Low-dose dexamethasone test has value as a
      discrimination test to distinguish dogs with PDH from those with ATH. The high
      dose test need only be considered in dogs with hyperadrenocorticism that do not
      have adrenal suppression in response to the low-dose test.

PMID- 8756879
TI  - Use of streptokinase in four dogs with thrombosis.
AB  - Four dogs with thrombosis were referred for diagnostic testing and were
      subsequently treated by the use of streptokinase. The range of duration of
      clinical signs associated with thrombosis was 6 to 120 days. Causes of thrombosis
      were heart disease (1 dog), protein-losing nephropathy and hyperadrenocorticism
      (1), hyperadrenocorticism (1), and idiopathic (1). Possible factors that
      predisposed dogs to hypercoagulability included hypertension (2 dogs) and
      diabetes mellitus (1). All dogs were treated for underlying disease by use of
      supportive care. The first dog was treated with a loading dose of 250,000 U of
      streptokinase, i.v., with a subsequent maintenance dosage of 100,000 U/h, i.v.,
      and also was treated with anticoagulant. The subsequent 3 dogs were treated with
      a loading dose of 90,000 U of streptokinase, i.v., and maintenance dosage of
      45,000 U/ h, i.v., at various intervals. These dogs also were treated with
      anticoagulant. Three dogs had minor hemorrhage as an adverse effect to
      streptokinase infusion, but they did not require treatment for the hemorrhage.
      Complete resolution of the thrombus was observed in 3 dogs, and partial
      resolution of the thrombus was observed in the other dog. In all dogs, partial or
      complete resolution of clinical signs associated with thrombosis was seen.
      Streptokinase may be an effective treatment for dogs with thrombosis.

PMID- 8756878
TI  - Ability of flumazenil, butorphanol, and naloxone to reverse the anesthetic
      effects of oxymorphone-diazepam in dogs.
AB  - OBJECTIVE: To evaluate the ability of flumazenil (FLU), butorphanol (BUT), and
      naloxone (NAL) to reverse the anesthetic effects of oxymorphone-diazepam in dogs.
      ANIMALS: 6 healthy adult mixed-bread dogs. PROCEDURE: Dogs were randomly assigned
      to each of 6 reversal treatment groups. In each experiment, oxymorphone (0.22
      mg/kg of body weight, i.v.) and diazepam (0.22 mg/kg. i.v.) were given
      sequentially 15 minutes after glycopyrrolate (0.01 mg/kg, i.v.) administration.
      Physiologic saline solution (SAL; 1 ml), FLU (0.01 mg/kg), BUT (0.44 mg/kg), or
      NAL (0.06 mg/kg) alone, or FLU-BUT or FLU-NAL (same dosages) was given i.v. as a
      reversal treatment 15 minutes after oxymorphone-diazepam administration. An
      individual unaware of the treatment protocol recorded time to extubation, sternal
      recumbency, and walking. RESULTS: Time to extubation was significantly (P < 0.05)
      less with BUT, NAL, FLU-BUT, or FLU-NAL treatment, compared with that for SAL
      treatment. Time to sternal recumbency was less with BUT, NAL, FLU-BUT, or FLU-NAL
      treatment, compared with that for SAL treatment. Time to walking was less with
      FLU-BUT or FLU-NAL treatment, compared with that for SAL treatment. CLINICAL
      IMPLICATIONS: Flumazenil, in combination with BUT or NAL, can be used to reverse
      the anesthetic effects of oxymorphone-diazepam in dogs.

PMID- 8756880
TI  - Tracheal resection and anastomosis for an intratracheal chondroma in a ball
      python.
AB  - A 9-year-old female ball python was evaluated for lethargy and respiratory
      compromise. Radiographic and endoscopic examination revealed a 1-cm intratracheal
      mass occluding the tracheal lumen. A partial tracheal resection and anastomosis
      was performed to remove the mass. On histologic examination, the mass was
      determined to be an intratracheal chondroma. Eosinophilic cytoplasmic inclusions
      observed within the tissue were calcium deposits. Electron microscopy was used to
      differentiate these from viral inclusion bodies often associated with neoplasms
      in reptiles. Endoscopic evaluation of the trachea 5 weeks after surgery revealed
      complete healing and minimal stenosis at the surgery site. Indications of tumor
      regrowth were not evident. Clinical signs of recurrence of respiratory compromise
      had not been observed 9 months after surgery.

PMID- 8756881
TI  - Squamous cell carcinoma of the midventral abdominal pad in three gerbils.
AB  - Squamous cell carcinoma of the midventral abdominal pad was diagnosed in 3 male
      gerbils. Two of the gerbils had raised, ulcerated masses on the midventral
      portion of the abdomen. The first gerbil was 2 years old, and an excisional
      biopsy was performed. The gerbil survived 23 months after surgery without
      evidence of metastasis or clinical signs of local recurrence. At necropsy,
      neoplastic squamous cells were seen on histologic examination of the surgery
      site. The second gerbil was 4 years old, and surgical excision of the tumor with
      concurrent castration was curative. The third gerbil was moribund on admission,
      perhaps because ulceration of the tumor may have allowed bacteria to invade the
      tissue, resulting in septicemia and disseminated intravascular coagulation. These
      gerbils illustrated that hematologic, radiographic, and biochemical testing in
      rodents can be useful and that excision of squamous cell carcinoma tumors of the
      midventral abdominal pad of gerbils can be an effective treatment.

PMID- 8756882
TI  - Juvenile renal disease in golden retrievers: 12 cases (1984-1994).
AB  - OBJECTIVE: To evaluate clinical and pathologic findings in Golden Retrievers with
      renal dysplasia. DESIGN: Retrospective study. ANIMALS: 12 young Golden Retrievers
      with chronic renal disease. PROCEDURE: Medical records of affected dogs were
      evaluated on the basis of clinical findings, laboratory test results, and
      histologic findings. RESULTS: Common clinical findings were vomiting, anorexia,
      weight loss, polydipsia, and polyuria. Common laboratory findings were azotemia,
      hyperphosphatemia, hypercholesterolemia, isosthenuria, proteinuria,
      hypercalcemia, and nonregenerative anemia. Many affected dogs also had urinary
      tract infections, and some were hypertensive. Renal lesions consisted of moderate
      to-severe interstitial fibrosis and mild-to-moderate lymphoplasmacytic
      interstitial inflammation. Cystic glomerular atrophy and periglomerular fibrosis
      were prominent features in most affected dogs. Fetal lobulation of glomeruli,
      adenomatoid hyperplasia of collecting tubule epithelium, and primitive
      mesenchymal connective tissue were histologic features suggestive of renal
      dysplasia. CLINICAL IMPLICATIONS: Renal dysplasia should be suspected in Golden
      Retrievers < 3 years old with clinical findings and laboratory results indicative
      of renal disease.

PMID- 8756883
TI  - Laryngeal and pharyngeal dysfunction in horses homozygous for hyperkalemic
      periodic paralysis.
AB  - OBJECTIVE: Evaluate histories, clinical signs, and laboratory data of 69 horses
      homozygous by DNA testing for hyperkalemic periodic paralysis (HPP). DESIGN:
      Cohort study. SAMPLE POPULATION: 69 of 189 horses testing homozygous for HPP
      between October 1992 and November 1994. PROCEDURE: Questionnaires addressing
      signalment, training regimes, medical history, and current status of affected
      horses were sent to owners, trainers, or attending veterinarians. Data from
      completed questionnaires were tabulated and evaluated, using descriptive
      statistics. RESULTS: Sixty-nine (37%) of 189 questionnaires were completed and
      returned. Clinical episodes of muscle weakness or paralysis varied in severity
      and frequency from mild muscle fasciculations to recumbency and death. Sixty
      three of 68 HPP-affected horses were reported to have had stridor associated with
      exercise, excitement, stress, or episodes of muscle paralysis. Common endoscopic
      findings in affected horses included pharyngeal collapse, pharyngeal edema,
      laryngopalatal dislocation, and laryngeal paralysis. Twelve of 27 horses
      receiving acetazolamide had decreases in stridor while receiving medication.
      CLINICAL IMPLICATIONS: Most horses testing homozygous for HPP had clinical signs
      associated with pharyngeal and laryngeal dysfunction. Hyperkalemic periodic
      paralysis should be included on a differential list for horses examined for signs
      of laryngeal or pharyngeal dysfunction or stridor. Treatment with acetazolamide
      may help to control respiratory tract signs associated with this disease.

PMID- 8756884
TI  - Corynebacterium pseudotuberculosis infection in horses: 538 cases (1982-1993).
AB  - OBJECTIVE: To describe clinical manifestations of Corynebacterium
      pseudotuberculosis infection in horses and to evaluate diagnostic methods for
      identification of this disease. DESIGN: Retrospective case series. ANIMALS: 538
      horses with a diagnosis of C pseudotuberculosis infection. RESULTS: Median age of
      horses with external abscesses was similar to that in horses with internal
      abscesses. Breed and sex did not appear to be associated with infection. Cases
      were detected during all 12 months; however, the disease was most common in the
      fall and early winter, with the highest incidence in September, October, and
      November in every year. Most horses (492/538, 91.4%) had a single episode of
      infection, without recurrence in subsequent years. Of 538 horses, 308 had
      pectoral abscesses, although infection was documented in many other anatomic
      locations. Forty-two horses had internal abscesses involving the abdomen or
      thoracic cavity. Corynebacterium pseudotuberculosis infection was readily
      identified by bacterial culture of aspirate samples from abscesses. The
      synergistic hemolysis inhibition test was useful for diagnosis of internal
      abscesses; however, it was unreliable for the diagnosis of external abscesses.
      Horses with external abscesses responded well to conventional treatment, in
      contrast to those with internal abscesses. The overall case fatality was low
      (3.9%), and was considerably lower for horses with external abscesses (0.8%) than
      for horses with internal abscesses (40.5%). CLINICAL IMPLICATIONS: Serology
      (synergistic hemolysis inhibition titers > or = 512) is useful for diagnosis of
      internal abscesses, but not reliable for diagnosis in horses with external
      abscesses. Prognosis for horses with internal abscesses is considerably poorer
      than for those with external abscesses.

PMID- 8756885
TI  - Risk factors associated with development of diarrhea in horses after celiotomy
      for colic: 190 cases (1990-1994).
AB  - OBJECTIVE: To determine the incidence of the risk factors for developing diarrhea
      in horses after celiotomy for colic. DESIGN: Retrospective cohort study. ANIMALS:
      357 adult horses that had celiotomy for colic at the teaching hospital between
      Jan 1, 1990 and Sep 1, 1994. PROCEDURE: Medical records of horses that had
      celiotomy for colic were reviewed to abstract information regarding development
      of diarrhea, signalment, history, and treatment. RESULTS: In horses that had
      celiotomy for colic, the incidence of diarrhea was 53.2% (190/357). Using
      multiple logistic regression, horses with a disorder of the large intestine were
      approximately twice as likely to develop diarrhea after celiotomy as horses that
      had surgery for other types of intestinal lesions (P < 0.001). Even after
      accounting for the effects of large intestinal surgery, horses that also had an
      enterotomy were approximately 1.5 times as likely to develop diarrhea (P =
      0.042). Diarrhea in horses associated with duration > 2 days, isolation of
      Salmonella spp from feces, or leukopenia was categorized as being severe.
      Incidence of severe diarrhea was 27.5% (98/357). Using multiple logistic
      regression, horses that had surgery of the large intestine were approximately 2.5
      times as likely to develop severe diarrhea after celiotomy as horses that had
      surgery for other types of intestinal lesions (P = 0.006). In horses that had
      celiotomy for colic, those that were fed grass hay were approximately half as
      likely to develop severe diarrhea as were horses that were not fed grass hay (P =
      0.018). CLINICAL IMPLICATIONS: Although the risk factors identified for the
      development of diarrhea are not alterable, knowledge of them will enable
      clinicians to better advise clients and to better prepare for medical management
      of horses after surgery.

PMID- 8756886
TI  - Relationships among treatment for respiratory tract disease, pulmonary lesions
      evident at slaughter, and rate of weight gain in feedlot cattle.
AB  - OBJECTIVE: To quantify the effects of treatment for clinical respiratory tract
      disease and pulmonary lesions identified at slaughter on rate of weight gain in
      feedlot cattle. DESIGN: Prospective longitudinal study. ANIMALS: 469 feedlot
      steers. PROCEDURE: Clinical respiratory tract disease was monitored between birth
      and slaughter. Steers were weaned at approximately 6 months old and entered into
      the feedlot for a mean of 273 days. Mean daily weight gain (MDG) was monitored
      during the feeding period. Lungs were collected at slaughter and evaluated for
      gross lesions indicative of active or resolved pneumonia. RESULTS: Mean daily
      weight gain during the feeding period was 1.30 kg, and ranged from 1.16 to 1.46
      kg within individual pens. Thirty-five percent of steers received treatment for
      respiratory tract disease between birth and slaughter, whereas 72% had pulmonary
      lesions evident at slaughter. Among steers treated for clinical respiratory tract
      disease, 78% had pulmonary lesions, whereas 68% of untreated steers had pulmonary
      lesions. Pulmonary lesions at slaughter were associated (P < 0.01) with a 0.076
      kg reduction in MDG during the feeding period. Treatment for clinical disease was
      not associated with MDG after adjustment for the effect of pulmonary lesions.
      CLINICAL IMPLICATIONS: Treatment of clinically affected feedlot cattle may be
      inadequate to prevent significant production losses attributable to respiratory
      tract disease.

PMID- 8756887
TI  - Tooth root abscesses in New World camelids: 23 cases (1972-1994).
AB  - OBJECTIVE: To determine typical clinical and radiographic findings in a group of
      New World camelids with tooth root abscesses and to determine outcome after
      medical and surgical treatment. DESIGN: Retrospective case series. ANIMALS: 23
      llamas and alpacas with radiographic and clinical evidence of tooth root
      abscesses. PROCEDURE: Disease history, signalment, physical and radiographic
      examination findings, bacteriologic culture results, treatment, and short-term
      and long-term outcome were retrieved from the medical records. RESULTS: Local
      swelling was the most common clinical abnormality in camelids with tooth root
      abscesses. Mandibular molars were affected most commonly, and bacteriologic
      culture of samples from lesions often revealed facultative anaerobic bacteria.
      Antibiotic treatment for at least 30 days, surgical extraction of the affected
      tooth, and a root canal procedure were used successfully to treat tooth root
      abscesses. CLINICAL IMPLICATIONS: Both surgical and medical treatment of tooth
      root abscesses may lead to successful resolution of clinical signs in New World
      camelids.

PMID- 8756889
TI  - Identity closure: a fifth identity status.
AB  - This study examined identity status and self-actualization of young adults (N =
      41), who were administered a revised identity interview (based on Marcia's
      interview) and a measure of self-actualization (the Personal Orientation
      Inventory). A fifth status, identity closure, was added to account for status
      regression and re-foreclosure, found in previous studies. This addition prompted
      a revision of the operational definition of identity achievement to include three
      criteria: exploration, tentative commitment, and openness to alternatives. Open
      achieved individuals scored higher than closed individuals on the measure of self
      actualization, suggesting some validity for the revised operational definition of
      identity achievement and providing support for Eriksonian theory. Theoretical
      implications and the development of a revised paradigm are discussed.

PMID- 8756888
TI  - Agreement among veterinarians evaluating gross lesions of lungs, livers, and
      nasal turbinates of pigs.
AB  - OBJECTIVE: To evaluate agreement between trained veterinarians and a reference
      inspector when recording gross lesions of lungs, livers, and nasal turbinates of
      pigs. DESIGN: Prospective study. SAMPLE POPULATION: 10 veterinarians in workshop
      1 and 11 veterinarians in workshop 2. PROCEDURE: Analysis of data obtained from 2
      workshops in which veterinarians evaluated fresh tissues (30 lungs and 30 livers)
      and 100 slides of nasal turbinates previously evaluated by the reference
      inspector. Veterinarians independently recorded observations of gross lesions.
      Agreement was evaluated by percentage agreement, kappa or weighted kappa, and
      sensitivity and specificity, where relevant. RESULTS: Agreement between
      veterinarians and the reference inspector was excellent for detecting
      consolidation of lung lobes typical of enzootic pneumonia (kappa = 0.81 and 0.87
      for workshops 1 and 2, respectively) and white spots on livers (kappa = 0.76 and
      0.78). Estimates of the extent of consolidation as a proportion of lung volume
      also agreed closely with reference values. Agreement was closer for veterinarians
      who had undergone repeated training and evaluation. Agreement was good for
      detecting nasal turbinate atrophy (weighted kappa = 0.63 and 0.68) and was
      poorest for detecting lesions of pleuritis (kappa = 0.39 and 0.44). CLINICAL
      IMPLICATIONS: For most of the lesions evaluated, acceptable levels of agreement
      with reference scores were achieved after training of veterinarians to use
      standardized methods to record gross lesions. Standardization of veterinarians'
      recordings of gross lesions should improve the reliability and usefulness of data
      collected by inspection of slaughtered pigs.

PMID- 8756890
TI  - The relation of prosocial and antisocial behavior to personality and peer
      relationships of Hong Kong Chinese adolescents.
AB  - The prosocial and antisocial behaviors of 2,862 Hong Kong Chinese adolescents
      were investigated. The major findings were as follows: (a) boys were more
      antisocial than girls: (b) negative peer influences were significantly stronger
      in boys than in girls, whereas positive peer influences were significantly
      stronger in girls than in boys; (c) antisocial adolescents tended to perceive
      their best friend as antisocial and exerting more negative influences on them,
      whereas prosocial adolescents tended to perceive their best friend as prosocial
      and exerting more positive influences on them; (d) antisocial behavior was
      positively associated with psychoticism and neuroticism; and (e) academic
      achievement tended to have a positive relation with prosocial behavior and a
      negative relation with antisocial behavior.

PMID- 8756891
TI  - Children's understanding of the distinction between real and apparent emotions: a
      training study.
AB  - The effects of two types of training on 4-year-old children's understanding of
      the distinction between experienced positive affect and neutral or negative
      display were examined. One type of training provided first-hand experience of
      possible discrepancies between facial expression and actual affect. The other
      training focused on the sorts of motives that might prompt the concealment of
      positive affect. Compared with a control group, both experimental groups showed
      modest gains.

PMID- 8756892
TI  - A note on adults' color-emotion associations.
AB  - The color-emotion associations of undergraduate students were analyzed. Twenty
      men and 20 women were asked to complete a self-administered questionnaire in
      which they listed their favorite color, the major color they were wearing, their
      emotional responses to colors, and the reasons for their choices. Responses
      showed that bright colors elicited mainly positive emotional associations, and
      dark colors elicited mainly negative emotional associations. Women responded more
      positively than men to bright colors, and they also responded more negatively to
      dark colors. Comparisons are made between the color-emotion associations of
      children and those of adults. The reasons for the color-emotion associations are
      discussed.

PMID- 8756893
TI  - Toddler adjustment: impact of parents' drug use, personality, and parent-child
      relations.
AB  - The intercorrelations among parents' drug use, personality, and parent-child
      relations and the child's anxious/regressive and reflective behaviors were
      investigated in a sample of 2-year-olds (N = 115). The results indicate that
      maternal child-rearing practices mediate the effect of maternal personality
      attributes on the child's intrapsychic functioning. The father's drug use had a
      direct influence on the child's reflective behavior. Generally, the mother's drug
      use, personality, and child-rearing practices were more important than the
      father's attributes. However, the father's drug use had a strong impact on the
      child when it interacted with the mother's drug use. Parental differences and
      implications for prevention are discussed.

PMID- 8756894
TI  - Children's assignment of gender to animal characters in pictures.
AB  - In previous research (DeLoache, Cassidy, & Carpenter, 1987), mothers'
      descriptions of gender-neutral animal characters were influenced by subtle gender
      stereo-types. The present research was an investigation of children's assignment
      of gender to the same neutral characters. The youngest children, 4 to 5 years
      old, usually assigned their own gender to the characters (bears). The 7- to 8
      year-old and 10- to 11-year-old children were influenced by gender stereotypes.
      Solitary or noninteracting bears were less likely to receive female gender labels
      than were bears involved in adult-child interactions. Boys in the oldest age
      group were most influenced by the stereotypes.

PMID- 8756895
TI  - Others' actions can reflect on the self: a developmental study of extended
      identity.
AB  - This study was an investigation of children's understanding that others'
      judgments of the self can be based on the actions of another person with whom one
      is associated. Five-, 8-, and 11-year-old children in Scotland were presented
      with hypothetical scenarios that indicated that they were responsible for a
      toddler who breached normative expectations of behavior. The children were
      required to make a variety of judgments, most notably concerning their likely
      emotion and its causes, and what others would think of them. The majority
      recognized that others would make negative judgments of the self. However,
      emotional self-attributions indicated that only among the 11-year-olds was there
      a widespread tendency to be self-punitive-that is, to attribute reflexive
      emotions such as embarrassment. Particularly among the 5-year-olds, punitive
      responses (e.g., anger) were directed only at the norm-violating toddler,
      implying that, unlike the oldest children, they did not view the toddler as
      constituting part of their extended identity. Eight-year-olds appeared to
      represent an intermediate step between the younger and older groups. In the light
      of these findings it is suggested that a mature form of extended identity may be
      a relatively late development.

PMID- 8756896
TI  - The experiential facilitation of memory development in the home environment.
AB  - Relationships among young children's home experiences, their memory knowledge,
      and their memory-task performance were examined. The participants were 78
      children in 2nd and 3rd grades and their families. The children were administered
      2 study-recall memory tasks and a memory-knowledge questionnaire. Home
      experiences were assessed with data gathered during a home visit and from a
      parents' self-report questionnaire. Specific home experiences that relate to the
      development of memory knowledge and memory-task performance were identified.
      Regression analyses supported a hypothesized theoretical model in which the
      influence of home experiences on memory-task performance is, at least partially,
      a function of the relationship between parents' requirements for self-regulation
      and self-responsibility and the development of children's knowledge about memory
      requirements and memory strategies.

PMID- 8756897
TI  - The development of metacognitive knowledge of basic motor skill: walking.
AB  - The development of children's metacognitive knowledge of walking was
      investigated. Sixty elementary school children (30 boys and 30 girls), 9, 11, and
      13 years of age, viewed a video presentation of an adult performing normal
      walking and six different forms of partial walking (varying in terms of the
      presence or absence of four essential features of normal walking: arm swing, leg
      swing, arm-leg coordination, and distance traveled). Then the children were asked
      to rate the partial walking. A repeated measures ANOVA revealed that children of
      all these ages appreciated the differences between normal walking and partial
      walking. As age increased, the degree of importance of the four features became
      more differentiated. By 13 years of age, the children considered leg swing to be
      the most important feature of walking, arm swing the second, arm-leg coordination
      the third, and distance traveled the least important feature.

PMID- 8756898
TI  - Future physician requirements: radiologists.

PMID- 8756899
TI  - Extravasation of radiographic contrast material: recognition, prevention, and
      treatment.

PMID- 8756900
TI  - Sequencing of chemotherapy and radiation therapy in the treatment of early breast
      cancer: the devil is in the details.

PMID- 8756901
TI  - Neutron therapy for pancreatic cancer: thirty years of unrealized promise.

PMID- 8756902
TI  - Will ferumoxides-enhanced MR imaging replace CT during arterial portography in
      the detection of hepatic metastases? Prologue to a promising future.

PMID- 8756903
TI  - Airways and lung: bronchography through the fiberoptic bronchoscope.

PMID- 8756904
TI  - Airways and lung: CT versus bronchography through the fiberoptic bronchoscope.

PMID- 8756905
TI  - Effect of delayed radiation therapy on local control in breast conservation
      therapy.
AB  - PURPOSE: To assess local control when radiation therapy is delayed to complete
      chemotherapy in breast conservation therapy. MATERIALS AND METHODS: Breast
      conservation therapy was performed in 310 cases in 297 patients (aged 24-85
      years) with stage 0-II breast cancer. Adjuvant chemotherapy was used in 76 cases.
      The authors analyzed the time between diagnosis and radiation therapy and
      correlated these findings with local control of disease. RESULTS: The time
      between diagnosis and radiation therapy in the 247 cases treated without
      chemotherapy-related delay was 2-59 weeks (mean, 8 weeks). The interval in the 63
      cases with chemotherapy-related delay was 12-63 weeks (mean, 31 weeks; P < .001).
      Ten of the 11 cases with an in breast relapse were in the group treated without a
      delay (P = .57). CONCLUSION: Delaying radiation therapy for chemotherapy does not
      compromise local control.

PMID- 8756906
TI  - Capsular contracture after lumpectomy and radiation therapy in patients who have
      undergone uncomplicated bilateral augmentation mammoplasty.
AB  - PURPOSE: To assess complications and cosmesis in patients with breast cancer who
      underwent lumpectomy and radiation therapy and who previously underwent
      uncomplicated bilateral augmentation mammoplasty. MATERIALS AND METHODS: Twenty
      one patients (aged 36-70 years; median age, 50 years) with breast cancer who had
      previously undergone bilateral breast augmentation without complications
      underwent ipsilateral lumpectomy and radiation therapy. Radiation therapy was
      delivered to the augmented breast in opposed tangential fields with a 4- or 6-MV
      linear accelerator. The tangential fields received an average radiation dose of
      5,021 cGy (range, 4,500-5,600 cGy), with an average fraction of 187 cGy (range,
      180- 200 cGy). Sixteen patients received an additional 1,000-2,000-cGy boost to
      the surgical bed with a 9-18-MeV electron beam. Follow-up was 4-48 months
      (median, 22 months). RESULTS: At the last follow-up examination, 18 (86%) of the
      21 patients were free of disease. Twelve patients had capsular contracture (57%).
      Seven patients underwent attempted surgical repair of capsular contracture.
      Twelve patients (57%) reported fair to poor cosmesis. The radiation dose, the
      location of the implant, the type of implant, and systemic therapy were not
      correlated with poor cosmesis. CONCLUSION: Lumpectomy and radiation therapy in
      patients with breast cancer who have previously undergone augmentation
      mammoplasty result in a high prevalence of capsular contracture and suboptimal
      cosmesis.

PMID- 8756907
TI  - Pancreatic cancer: treatment with neutron irradiation alone and with
      chemotherapy.
AB  - PURPOSE: To evaluate neutron irradiation alone and with chemotherapy to treat
      inoperable pancreatic cancer. MATERIALS AND METHODS: Between 1977 and 1994, 173
      patients (60 men, 113 women, aged 43-77 years [mean, 59 years]) with unresectable
      adenocarcinoma of the exocrine pancreas were treated, 106 with neutron
      irradiation alone and 67 with concomitant chemotherapy (fluorouracil [5-FU]). At
      follow-up, which was performed at 2-month intervals until death (range, 4-64
      months), clinical status was recorded, noting the presence of overt metastasis
      and the onset of any major complications. Actuarial (Kaplan-Meier) survival
      tables were computed for both groups. RESULTS: For neutron irradiation alone and
      neutron irradiation plus chemotherapy, median survival times were 6 months and 9
      months, respectively; actuarial survival rates at 3 years were 0 and 7%,
      respectively; major reactions (grade 3 or higher [scale of the Radiation Therapy
      Oncology Group and European Organization for Research and Treatment of Cancer])
      occurred in 19 (18%) and 17 (25%) patients, respectively; and severe
      complications (grade 4) occurred in five (5%) and four (6%) patients,
      respectively. Most deaths were due to metastatic disease rather than to failure
      of local control. CONCLUSIONS: Neutron irradiation obliterated pancreatic
      adenocarcinoma at the primary site but has no effect on long-term survival. With
      more effective concomitant chemotherapy to prevent metastasis, local control of
      pancreatic cancer with neutron irradiation could lead to increased long-term
      survival.

PMID- 8756908
TI  - Contrast-enhanced CT: value for diagnosing local breast cancer recurrence after
      conservative treatment.
AB  - PURPOSE: To assess contrast material-enhanced computed tomography (CT) of breast
      for diagnosing local recurrence after conservative therapy. MATERIALS AND
      METHODS: In 111 patients, 118 lesions were evaluated with unenhanced and enhanced
      CT. Criterion for cancer recurrence was detection of a lesion with an enhancement
      of 45 HU or more. RESULTS: One group comprised 52 lesions with pathologic
      diagnoses, obtained within 1 month of CT, of malignancy in 43 and benignancy in
      nine. Scans were positive in 40 of 43 recurrences and negative in six of nine
      benign lesions. Seventeen recurrent lesions were nonpalpable, and contrast
      enhanced CT results were true-positive in 15 of these. A second group comprised
      66 lesions with a mean follow-up of the treated breast of 28 months after CT. In
      56 lesions, the scans were negative, with no recurrence in 55; local recurrence
      was proved with a 14-month delayed surgical biopsy in one. In 10 lesions, scans
      were positive, with a delayed diagnosis of recurrence 5 and 6 months after CT in
      two and no evidence of recurrence in eight (false-positive results). The
      sensitivity of breast CT for both groups was 91% (42 of 46 lesions) with a
      specificity of 85% (61 of 72 lesions). CONCLUSION: Contrast-enhanced CT is
      sensitive in the diagnosis of local recurrence of breast cancer, even in
      nonpalpable lesions, and may be a useful tool in patients with equivocal clinical
      and/or mammographic findings during follow-up after conservative therapy.

PMID- 8756909
TI  - Breast lesions: correlation of contrast medium enhancement patterns on MR images
      with histopathologic findings and tumor angiogenesis.
AB  - PURPOSE: To compare qualitative and quantitative magnetic resonance (MR)
      mammographic features of breast lesions with histopathologic findings, especially
      tumor angiogenesis. MATERIALS AND METHODS: Seventy-three patients (72 women, one
      man; aged 30-78 years; mean age, 51.0 years) with suspicious breast lesions
      underwent MR imaging. Noncontrast medium-enhanced localization imaging and then
      gadolinium-enhanced dynamic fast spoiled gradient-recalled-echo (SPGR) imaging
      were performed in all patients. In selected patients, subtraction fast SPGR
      images were obtained. The Pearson and Spearman correlation tests were used to
      determine the strength of the relationships between enhancement parameters and
      microvessel determinations. RESULTS: Time intensity curve type correlated with
      microvessel density grade (Spearman rank correlation test: r = .90, P < .001).
      The steepest slope of contrast medium uptake correlated with microvessel counts
      (Pearson correlation test; r = .83, P < .001). Peripheral enhancement in invasive
      carcinomas (n = 9) correlated with high peripheral and low central microvessel
      densities, which were associated with desmoplasia and/or necrosis. Internal
      septations (n = 2) were seen only in fibroadenomas. CONCLUSION: The density and
      distribution of microvessels may play major roles in the determination of the
      initial rate of contrast medium uptake and the heterogeneity of tumor
      enhancement.

PMID- 8756910
TI  - Laser therapy for breast cancer: MR imaging and histopathologic correlation.
AB  - PURPOSE: To investigate magnetic resonance (MR) imaging guidance of interstitial
      laser photocoagulation to treat primary breast cancer. MATERIALS AND METHODS:
      Twenty female patients with symptomatic breast cancers diagnosed at cytologic
      examination underwent interstitial laser photocoagulation by means of a single
      fiber prior to surgical excision. Gadolinium-enhanced T1-weighted three
      dimensional fast low-angle shot (FLASH) MR imaging was performed before and after
      laser therapy (median, 48 hours; range, 24-96 hours). Following resection, tumors
      were mapped in detail histopathologically. The extent of disease, size of laser
      burn, and extent of residual tumor were correlated with MR findings. RESULTS:
      Twenty-seven tumors were detected at histopathologic examination in the 20
      patients. Five patients had more than one invasive mass. Twenty-five of the 27
      tumors were identified as discrete enhancing masses at MR. The two missed
      invasive foci were obscured on MR images by diffuse patchy enhancement that
      correlated with the presence of an associated extensive intraductal component.
      Early (4-hour) follow-up images failed to depict the laser effect. Later (24-96
      hours) follow-up images depicted the laser-induced necrosis as a zone of
      nonenhancement within the residual enhancing tumor. The correlation coefficients
      (MR vs histopathologic analysis) for the laser-burn diameter and residual tumor
      were 0.80 and 0.86, respectively. CONCLUSION: Delayed gadolinium-enhanced MR
      images can help define the extent of laser-induced necrosis and residual tumor
      after interstitial laser photocoagulation therapy in breast cancer.

PMID- 8756911
TI  - Mammographic phantom studies with synchrotron radiation.
AB  - PURPOSE: To explore the potential improvement in image contrast for breast
      imaging with use of monoenergetic photons. MATERIALS AND METHODS: The x-ray
      energy available from the National Synchrotron Light Source is from 5 to over 50
      keV. A specific energy is selected with a tunable crystal monochromator. The
      object is scanned with a narrow beam of 80.0 x 0.5 mm. Mammography phantoms were
      imaged with plate and film as the imaging detectors. Phantom images were obtained
      at 16-24 keV and compared with images obtained with a conventional mammographic
      unit. RESULTS: Preliminary findings indicate improved image contrast of the
      monoenergetic images compared with that obtained from the conventional x-ray
      source, particularly at 18 keV and below. CONCLUSION: Pilot results are
      encouraging, and the authors presently continue to explore monoenergetic photon
      imaging with improved instrumentation, scatter rejection, and use of tissue
      samples.

PMID- 8756912
TI  - Sliding thin slab, minimum intensity projection technique in the diagnosis of
      emphysema: histopathologic-CT correlation.
AB  - PURPOSE: To assess the accuracy of sliding thin slab, minimum intensity
      projection technique in the detection of emphysema. MATERIALS AND METHODS: In 29
      patients without radiographic evidence of emphysema and who were undergoing lung
      resection, focal spiral computed tomography (CT) was performed in the lobe to be
      resected. Ten contiguous 1-mm-thick CT scans and sliding thin slab, minimum
      intensity projection images with slab thicknesses of 3-, 5-, and 8 mm were
      generated. From each image, the presence and extent of emphysema were recorded
      before histopathologic analysis was performed. To familiarize readers with the
      appearance of normal lung parenchyma on sliding thin slab, minimum intensity
      projection images, five asymptomatic volunteers underwent scanning with a similar
      protocol. RESULTS: Emphysema was present on both thin-section CT scans and
      sliding thin slab, minimum intensity projection images in 13 patients. In all
      cases, sliding thin slab, minimum intensity projection images improved
      conspicuity of small areas of hypoattenuation. When thin-section CT scans were
      negative (n = 16), sliding thin slab, minimum intensity projection images enabled
      identification of focal zones of hypoattenuation in four cases with histologic
      confirmation of emphysema. Sensitivity of thin-section CT (62%) and sliding thin
      slab, minimum intensity projection technique (81%) were significantly different
      (P < .01); specificity for both was 100%. Emphysema was easier to detect on 8-mm
      thick slabs because of better suppression of vascular structures. CONCLUSION: The
      sliding thin slab, minimum intensity projection technique enabled improved
      detection of mild forms of emphysema.

PMID- 8756913
TI  - Bronchiectasis: comparative assessment with thin-section CT and helical CT.
AB  - PURPOSE: To compare thin-section computed tomography (CT) and helical CT in the
      detection and assessment of the extent of bronchiectasis. MATERIALS AND METHODS:
      Both thin-section and helical CT scans were obtained in 50 consecutive patients
      with clinical symptoms suggestive of bronchiectasis. Thin-section CT was
      performed with 1.5-mm collimation and 10-mm intervals, and helical CT was
      performed with 3-mm collimation and a pitch of 1.6 during a 24-second breath
      hold. Three observers evaluated 593 segments on CT scans both independently and
      in consensus. Radiation dose was measured for both techniques. RESULTS:
      Bronchiectasis was noted in 77 segments (22 patients) on thin-section CT scans
      compared with 90 segments (26 patients) on helical CT scans. No findings were
      positive for bronchiectasis on only thin-section CT scans. Interobserver
      agreement was statistically significantly better (P < .05) in identification of
      segments that were positive for bronchiectasis on helical CT scans (kappa = 0.87)
      than on thin-section CT scans (kappa = 0.71). Total skin dose of radiation
      delivered with helical CT was 3.4 times greater than that delivered with thin
      section CT. CONCLUSION: Helical scanning can improve CT depiction of
      bronchiectasis but with an increase in radiation exposure to the patient. It
      should be used in patients considered for surgery or for thin-section CT scans
      that are difficult to interpret.

PMID- 8756914
TI  - Solitary pulmonary nodules: MR evaluation of enhancement patterns with contrast
      enhanced dynamic snapshot gradient-echo imaging.
AB  - PURPOSE: To evaluate the enhancement patterns of solitary pulmonary nodules
      (SPNs) with dynamic contrast-material-enhanced magnetic resonance (MR) imaging to
      differentiate between benign and malignant SPNs. MATERIALS AND METHODS: Twenty
      eight patients with SPNs 30 mm or smaller in diameter were examined with pre- and
      postcontrast, electrocardiographically gated, T1-weighted spin-echo (SE)
      sequences and a snapshot gradient-echo (GRE) sequence after bolus injection of a
      paramagnetic contrast agent. For all SPNs (20 malignant, eight benign), the
      percentage increase in signal intensity (%SI) on the postcontrast T1-weighted SE
      images and the enhancement curves (%SI/sec) for the snapshot GRE measurements
      were established from regions of interest. RESULTS: Malignant nodules showed a
      higher increase of signal intensity during the first transit of the bolus of
      contrast material on the dynamic snapshot GRE images (malignant: median, 18.1
      %SI/sec; range, 6.7-95.2 %SI/sec; benign: median, 2.3 %SI/sec; range, 0.1-8.1
      %SI/sec) (P < .0001). Static T1-weighted SE measurements did not allow
      differentiation between malignant (median, 53.4 %SI; range 12.5-110.0 %SI) and
      benign (median, 33 %SI; range, 0.8-85.5 %SI) (P > .2) nodules on the basis of the
      degree of contrast enhancement. CONCLUSION: Dynamic contrast-enhanced MR
      measurements of tumor enhancement can provide additional information about the
      nature of SPNs.

PMID- 8756915
TI  - Chest imaging with a selenium detector versus conventional film radiography: a CT
      controlled study.
AB  - PURPOSE: To compare radiologist detection performance under clinical conditions
      for assessment of conventional radiographs and digital chest images obtained with
      a selenium detector. MATERIALS AND METHODS: One hundred four patients were
      examined with the digital and conventional systems under near identical technical
      conditions. The digital images were acquired without an antiscatter grid. Two
      hundred eight images were analyzed by three radiologists for detection of
      pulmonary, mediastinal, and pleural abnormalities; computed tomography was used
      as the reference standard. The diagnostic value of both techniques for the
      detection of these chest abnormalities was analyzed with receiver operating
      characteristic (ROC) methods. RESULTS: For detection of the various abnormalities
      by all radiologists, the areas under the ROC curves with conventional imaging
      versus digital imaging, respectively, were as follows: pulmonary opacities, 0.81
      versus 0.79; interstitial disease, 0.69 versus 0.73; mediastinal disease, 0.79
      versus 0.74; and pleural abnormalities, 0.73 versus 0.68. CONCLUSION: There was
      no statistically significant difference between the radiologists' performance in
      detecting pulmonary, mediastinal, and pleural abnormalities with conventional
      radiography versus that with digital selenium chest radiography.

PMID- 8756916
TI  - Massive hemoptysis due to pulmonary tuberculosis: control with bronchial artery
      embolization.
AB  - PURPOSE: To determine the efficacy of bronchial artery embolization in the
      control of massive hemoptysis due to pulmonary tuberculosis. MATERIALS AND
      METHODS: Between 1988 and 1994, 140 patients (125 men and 15 women; mean age,
      31.5 years) who presented with massive hemoptysis (more than 300 mL of blood in
      24 hours) underwent bronchial artery embolization. Fifty-one patients had
      received no antituberculosis drugs. Bronchial artery embolization was performed
      on the side with the greater abnormality on the chest radiograph. Catheters (4 F)
      and a gelatin sponge were used for embolization. Inflammatory hypervascularity
      was seen in all patients (five patients had contrast material extravasation and
      10 patients had pseudoaneurysms). RESULTS: Almost complete control of hemoptysis
      was achieved in 102 patients. Of the remaining 38 patients with a notable amount
      of bleeding after the procedure, 29 were treated successfully with conservative
      measures and nine underwent re-embolization. Seven patients who underwent re
      embolization had recurrent bleeding; four of these patients underwent successful
      surgery, and three died of aspiration. Two patients developed transient
      paraparesis 6 hours after the procedure. Nine patients reported transient
      referred pain to the ipsilateral orbit during injection of the gelatin sponge.
      One patient had transient dysphagia. CONCLUSION: Patients with massive hemoptysis
      due to pulmonary tuberculosis should first be treated with bronchial artery
      embolization.

PMID- 8756917
TI  - Aspiration of a large pneumothorax resulting from transthoracic needle biopsy.
AB  - PURPOSE: To determine whether simple aspiration of air from the pleural space
      could obviate chest tube placement in patients with a large pneumothorax after
      transthoracic needle biopsy. MATERIALS AND METHODS: Seventeen patients, who
      developed a large pneumothorax (> 30%) during computed tomographic (CT)-guided
      transthoracic needle biopsy and otherwise would have required chest tube
      placement, underwent percutaneous aspiration of the pneumothorax while on the CT
      scanner table. Air was aspirated from the pleural space by using an 18-gauge
      intravenous catheter attached to a three-way stopcock and a 50-mL syringe. The
      patients were positioned with the puncture site down after aspiration of the
      pneumothoraces and oxygen was administered both during and after the procedure.
      RESULTS: The pneumothorax was almost completely aspirated in all 17 patients.
      Twelve (70%) patients did not require chest tube placement. Follow-up chest
      radiographs obtained 2 and 4 hours after the procedure revealed complete or
      almost complete resolution of the pneumothorax in eight (47%) patients and
      partial recurrence of a small, stable pneumothorax in four (24%) patients. The
      remaining five (29%) patients had recurrence of their pneumothorax, which
      ultimately required chest tube placement. CONCLUSION: Percutaneous catheter
      aspiration of a large biopsy-induced pneumothorax is safe and easy to perform and
      may obviate chest tube placement.

PMID- 8756918
TI  - Diagnosis of pulmonary embolism with spiral CT: comparison with pulmonary
      angiography and scintigraphy.
AB  - PURPOSE: To evaluate the accuracy of spiral computed tomography (CT) in the
      noninvasive diagnosis of pulmonary embolism (PE). MATERIALS AND METHODS: A
      prospective study was performed in 75 patients who were evaluated with spiral CT
      and pulmonary angiography of each lung to detect central PE; 25 of the patients
      also underwent ventilation-perfusion (V-P) scanning. RESULTS: Spiral CT scans
      were technically suboptimal in three patients. CT and angiographic findings were
      negative for PE in 25 patients; one patient had false-negative CT findings.
      Findings from both studies were positive in 39 patients. CT findings of 188
      central emboli corresponded exactly to those of angiography. Ten emboli were
      depicted only on CT scans, whereas seven emboli were identified only on
      angiograms because of inadequate depiction of the pulmonary arteries in the plane
      of the CT scans (n = 5) or because of misinterpretation of CT findings (n = 2).
      The prospective sensitivity of CT was 91%, the specificity was 78%, the positive
      predictive value was 100%, and the negative predictive value was 89%. Technical
      failures (n = 3) and inconclusive CT findings (n = 7) were the major limitations
      of spiral CT. Spiral CT enabled accurate classification of PE in 16 patients with
      indeterminate (n = 7) and low (n = 9) probability of PE on V-P scans. CT
      demonstrated central PE in two patients with normal V-P scans. CONCLUSION: Spiral
      CT can reliably depict central PE and may be introduced into the classic
      diagnostic algorithms.

PMID- 8756919
TI  - Comparison of portal vein anatomy and bony anatomic landmarks.
AB  - PURPOSE: To determine if a relationship exists between the right portal trunk
      (RPT) and bony structures that might aid guidance of needle passes into the RPT
      during transjugular intrahepatic portosystemic shunt (TIPS) placement. MATERIALS
      AND METHODS: Sixty-two TIPS portal venograms were reviewed. The distance of the
      mid-RPT from the lateral margin of the vertebral column was measured and
      calculated as a fraction of the adjacent vertebral body width. The cephalocaudal
      height of the RPT was compared with that of the posterior ribs and rib spaces.
      The cephalocaudal height was evaluated with frequency distribution, and
      scattergram plots were used to determine the most common location of the mid-RPT
      relative to bony structures. The height and lateral position were analyzed in
      relation to clinical parameters to determine the effect of these parameters on
      RPT position. RESULTS: The mean distance of the mid-RPT from the lateral
      vertebral margin was 0.9 vertebral widths (range, 0.1-1.5). Fifty-six of 62 (90%)
      mid-RPTs were between 0.5 and 1.5 vertebral widths to the right of the lateral
      margin of the vertebrae. Fifty-four of 62 (87%) mid-RPTs were below the 10th and
      above the 12th ribs. Clinical factors did not affect RPT position. CONCLUSION:
      Bony landmarks provide an approximation of the mid-RPT location and may aid in
      TIPS placement.

PMID- 8756920
TI  - Mechanical thrombolysis for the treatment of thrombosed hemodialysis access
      grafts.
AB  - PURPOSE: To evaluate the data acquired over 2 1/2 years regarding the use of
      mechanical thrombolysis as the routine, preferred treatment for thrombosed access
      grafts in a large patient population undergoing hemodialysis. MATERIALS AND
      METHODS: Mechanical thrombolysis was performed in 1,176 cases. Data were
      collected on the success rate, complication rate, long-term patency, and presence
      and location of stenosis. The results of mechanical thrombolysis were compared
      with those of surgery. All data were collected prospectively. RESULTS: Thrombosed
      grafts were treated successfully in 1,123 of 1,176 cases (95%). Minor
      complications occurred in 34 cases (3%). Venous stenosis was present in 1,054
      cases (90%). Long-term patency rates were 74% at 30 days, 52% at 90 days, and 17%
      at 360 days. The thrombosis rate per patient per year and the number of patients
      who required graft revision or replacement decreased in comparison with the
      results obtained with surgical treatment. CONCLUSION: Mechanical thrombolysis was
      effective, quick, and safe. Percutaneous treatment should be adopted as the
      treatment of choice for thrombosed hemodialysis access grafts.

PMID- 8756922
TI  - Hepatic artery: variability in measurement of resistive index and systolic
      acceleration time in healthy volunteers.
AB  - PURPOSE: To determine the intrinsic sampling variability of measurements of
      hepatic artery resistive index and systolic acceleration time in healthy subjects
      and to estimate the components of variability attributable to the sonographer,
      individual measurement, and subject. MATERIALS AND METHODS: In a randomized,
      controlled (blinded) fashion, nine sonographers measured hepatic artery resistive
      index and systolic acceleration time in five healthy subjects by using Doppler
      ultrasound (US). Analysis of variance was used to estimate the contribution of
      several factors to the observed variability in measurements. RESULTS: The
      standard deviation for a single measurement was 0.08 for resistive index and 39
      msec for systolic acceleration time. For resistive index, the estimated variance
      components were 0.0012 (18%), 0.0004 (6%), and 0.0050 (76%) for the subject,
      sonographer, and intrinsic variability, respectively. For systolic acceleration
      time, the estimated variance components were 59 msec (4%), 264 msec (17%), and
      1,250 msec (79%) for the subject, sonographer, and intrinsic variability,
      respectively. CONCLUSION: Because of substantial variability in hepatic arterial
      measures, caution is indicated when interpreting small changes in the measurement
      of these Doppler US indexes.

PMID- 8756921
TI  - Malignant biliary duct obstruction: long-term experience with Gianturco stents
      and combined-modality radiation therapy.
AB  - PURPOSE: To evaluate the effect of combined-modality therapy including
      intraluminal iridium-192 on stent patency and survival in patients with malignant
      biliary obstruction treated with Gianturco stents. MATERIALS AND METHODS: Twenty
      two patients with unresectable biliary obstruction caused by cholangiocarcinoma
      (n = 11) or by secondary extrahepatic bile duct malignant tumors (n = 11) were
      treated with percutaneous biliary drainage followed by intraluminal Ir-192 wire
      placement (mean dose, 25 Gy) before insertion of Gianturco metal stents. Eleven
      patients also received external-beam radiation therapy, and 13 patients received
      chemotherapy. Patency was defined as absence of jaundice or cholangitis that
      necessitated hospitalization, or as seen on hepatobiliary scans. Survival was
      determined from the time of stent insertion after brachytherapy. RESULTS:
      Patients with cholangiocarcinoma had extended mean stent patency of 19.5 months
      (range, 2-46 months) and mean survival of 22.6 months (range, 2-72 months).
      Patients with secondary malignant tumors had a mean patency of 4.8 months (range,
      1.5-8 months) and a mean survival of 5.3 months (range, 2-9 months). CONCLUSION:
      Radiation therapy including intraluminal Ir-192 appears to extend stent patency
      and survival in patients with inoperable cholangiocarcinoma treated with
      Gianturco metal stents compared with patients with other extrahepatic bile duct
      malignant diseases and patients treated without combined-modality therapy in
      other studies.

PMID- 8756923
TI  - Power injection of intravenous contrast material through central venous catheters
      for CT: in vitro evaluation.
AB  - PURPOSE: To determine the feasibility of use of a power injector to deliver
      contrast material through central venous catheters for computed tomographic (CT)
      examinations. MATERIALS AND METHODS: Ioversol 240 and iothalamate meglumine 43%
      were separately injected through three 9.6-F Hickman catheters and three 10.0-F
      Leonard catheters with a power injector in an in vitro study. Flow rates of 1.0,
      1.5, 2.0, and 2.5 mL/sec were tested. Peak pressures were mechanically recorded
      from two sites. A 95% prediction interval was calculated for each peak pressure,
      and the upper limits at the prediction interval were evaluated to determine if it
      was less than the recommended limit of 25 psi (175 kPa). RESULTS: Contrast
      medium, flow rate, and catheter type each statistically significantly affected
      the measured peak pressures (P = .0001). For each flow rate tested, the upper
      limits of the prediction interval for the peak pressure at the connection between
      the coiled tubing and the catheter were below the manufacturer's specified peak
      pressure. CONCLUSION: In vitro analysis demonstrates that power injection of
      intravenous contrast medium through central venous catheters does not exceed the
      pressure limits of these catheters at the flow rates tested. In vivo testing to
      evaluate the safety and efficacy of power injection through central venous
      catheters is necessary.

PMID- 8756924
TI  - Delayed enhanced CT for differentiation of benign from malignant adrenal masses.
AB  - PURPOSE: To determine whether adenomas can be differentiated from nonadenomas on
      1-hour-delayed enhanced computed tomographic (CT) scans. MATERIALS AND METHODS:
      In a prospective evaluation of 51 adrenal masses in 39 patients, the CT
      attenuation was measured at the time of contrast enhancement and 1 hour later.
      The results were compared for adenomas (n = 41) and metastases (n = 10). RESULTS:
      On 1-hour-delayed enhanced CT scans, the mean attenuation of the adenomas was 11
      HU +/- 13 versus 49 HU +/- 8.3 for metastases (P < .001). At a threshold value of
      30 HU, specificity and positive predictive value for the diagnosis of adenoma
      were 100% with a sensitivity of 95%. The mean decrease in attenuation during the
      1-hour delay was 74% +/- 37 for the adenomas versus 31% +/- 28 for the metastases
      (P < .001). CONCLUSION: CT densitometry on delayed scans obtained 1 hour after
      contrast enhancement may be useful in characterizing an adrenal mass as an
      adenoma. When CT is performed with a 150-mL bolus injection of contrast material
      and with the scanning parameters described in this study, other procedures or
      imaging studies may be unnecessary if the mass measures less than 30 HU on the
      delayed scans.

PMID- 8756925
TI  - Adrenal adenomas: relationship between histologic lipid and CT and MR findings.
AB  - PURPOSE: To assess the relationship between the quantity of lipid in resected
      adrenal adenomas and the unenhanced computed tomographic (CT) attenuation number
      and the relative change in signal intensity on chemical shift magnetic resonance
      (MR) images. MATERIALS AND METHODS: The percentage of lipid-rich cortical cells
      in histologic sections from 20 resected adrenal adenomas was assessed. The
      results were correlated with the corresponding unenhanced CT attenuation number
      or the relative change in signal intensity on chemical shift MR images, or both.
      RESULTS: There was an inverse linear relationship between the percentage of lipid
      rich cortical cells in the adrenal adenomas and the unenhanced CT attenuation
      number (R2 = .68, P = .0005). There was a similar inverse linear relationship to
      the relative change in MR signal intensity on chemical shift images by using both
      quantitative (R2 = .83, P = .004) and qualitative (R2 = .70, P = .019)
      assessment. CONCLUSION: The presence and amount of histologic lipid in many
      adrenal adenomas accounts for their low attenuation on unenhanced CT scans and
      their loss in relative signal intensity on chemical shift MR images.

PMID- 8756926
TI  - Adrenal masses: correlation between CT attenuation value and chemical shift ratio
      at MR imaging with in-phase and opposed-phase sequences.
AB  - PURPOSE: To correlate attenuation values at computed tomography (CT) with signal
      intensity at chemical-shift magnetic resonance (MR) imaging in adrenal masses.
      MATERIALS AND METHODS: Thirty-eight patients with 47 adrenal lesions underwent MR
      imaging and unenhanced CT examinations. MR examinations, performed at 1.5 T,
      included T1-weighted imaging with fat and water in phase and gradient-echo
      imaging with fat and water out of phase (repetition time, 45-180 msec; echo time,
      1.4-3.1 msec). Lesion-to-spleen signal intensity ratios were calculated for the
      in-phase and opposed-phase images. The chemical-shift ratio, a measure of signal
      intensity loss between in-phase and opposed-phase images, and the CT attenuation
      value (in Hounsfield units) were determined for each lesion. RESULTS: A
      statistically significant correlation (0.85) was found between attenuation and
      chemical-shift-ratio values (P < .000001). Attenuation in six benign lesions was
      within 2 standard deviations of the mean attenuation in malignant lesions, and
      the chemical-shift ratio in eight benign lesions was within 2 standard deviations
      of the mean chemical-shift ratio in malignant lesions. Six of these eight lesions
      were misclassified on the basis of both attenuation and chemical-shift-ratio
      values. CONCLUSION: CT attenuation values are highly correlated with chemical
      shift ratios. Both values were indeterminate for a similar subset of benign
      lesions.

PMID- 8756927
TI  - Multiphasic renal CT: comparison of renal mass enhancement during the
      corticomedullary and nephrographic phases.
AB  - PURPOSE: To evaluate thin-section computed tomography (CT) performed during the
      corticomedullary and nephrographic phases of contrast material enhancement in the
      characterization of renal masses. MATERIALS AND METHODS: A prospective study of
      30 patients was undertaken with CT to characterize 31 "indeterminate" renal
      masses. In all patients, 5-mm-thick, contiguous, high-tube-current (320-340-mA)
      scans were obtained through the kidneys before (axial mode), during (helical
      mode, 25-second delay, corticomedullary-phase images), and after (axial mode, 120
      second delay, nephrographic-phase images) administration of a 117-second biphasic
      injection of intravenous contrast material. RESULTS: Eight of 16 neoplasms
      measured less than 20 HU on CT scans obtained without contrast material
      enhancement; measurements of two of these corresponded to "cyst attenuation"
      during the corticomedullary phase. Enhancement of 10 HU or greater was
      demonstrated in 11 neoplasms during the corticomedullary phase and in all
      neoplasms in the nephrographic phase. No enhancement was seen in 15
      radiologically benign cysts. Both renal neoplasms and normal renal cortex
      demonstrated significantly greater enhancement in the nephrographic phase
      compared with that in the corticomedullary phase (P = .0002 and P < .0001,
      respectively). CONCLUSION: Enhancement of renal neoplasms is time dependent and
      may not be evident in hypovascular tumors analyzed during the early
      corticomedullary phase. Reliance on absolute CT attenuation measurements, without
      use of internal standards as controls, may lead to misdiagnosis of neoplasms as
      cysts.

PMID- 8756928
TI  - Nonsurgical placement of a nasolacrimal polyurethane stent: long-term
      effectiveness.
AB  - PURPOSE: To evaluate the long-term effectiveness of a polyurethane stent in the
      treatment of obstruction of the lacrimal sac and the nasolacrimal duct. MATERIALS
      AND METHODS: Fluoroscopically guided placement of a polyurethane nasolacrimal
      stent was evaluated in 283 obstructed lacrimal systems of 236 patients, with a
      follow-up period of more than 1 year (range, 52-134 weeks). The obstruction was
      at the junction between the lacrimal sac and the nasolacrimal duct in 192
      systems, at the lacrimal sac in 52, and at the nasolacrimal duct in 39. The
      causes of obstruction were traumatic in 34 and idiopathic in 249 systems.
      RESULTS: Stent placement was technically successful in 270 systems (95%). At 7
      days after stent placement, 235 (87%) of the 270 systems with successful
      placement demonstrated complete resolution of epiphora, 27 (10%) had partial
      resolution, and the remaining eight (3%) had no resolution. There was recurrence
      in 81 systems due to obstruction of the stent (n = 77) or obstruction of the
      common canaliculus (n = 4). The recurrence rate was much higher in the systems
      with obstruction at the lacrimal sac (64%) than in the systems with obstruction
      at the junction (26%) between the lacrimal sac and nasolacrimal duct or at the
      nasolacrimal duct (15%). CONCLUSION: Stent placement in the obstructed lacrimal
      system below the junction between the lacrimal sac and the nasolacrimal duct is
      valuable as an initial therapy.

PMID- 8756929
TI  - Postmyelography headache: a review.
AB  - The author reviews the topic of postdural puncture headache (PDPH) so
      radiologists can better understand, prevent, and treat this common complication
      of myelography. PDPH, a postural headache relieved by lying supine, occurs after
      36.0%-58.2% of myelographic procedures performed with 22-gauge Quincke needles.
      It begins within 3 days and lasts 3-5 days. Thin, young women are more likely to
      develop PDPH. Smaller gauge needles, blunt-tip needles, a paramedian approach,
      and parallel orientation of a bevel needle are associated with lower PDPH rates.
      Intravenous hydration, no removal of cerebrospinal fluid, experience of the
      myelographer, and inpatient status have been inconsistently associated with lower
      PDPH rates. Treatment is supportive with bed rest. Oral or intravenous
      methylxanthine agents may be given for more severe PDPH. An epidural blood patch,
      although rarely needed, is very effective.

PMID- 8756930
TI  - Postmyelography headache rates with Whitacre versus Quincke 22-gauge spinal
      needles.
AB  - PURPOSE: To compare the postdural puncture headache (PDPH) rates after
      myelography with use of 22-gauge Whitacre (blunt tip) versus standard 22-gauge
      Quincke (bevel-tip) spinal needles. MATERIALS AND METHODS: At myelography, 340
      patients were randomly assigned to one of two groups in which either the Whitacre
      (167 patients) or the Quincke (173 patients) needle was used. Follow-up was at 48
      hours and at 4 days after the procedure. Crude and adjusted Whitacre/PDPH odds
      ratios and risk ratios were calculated. RESULTS: The crude Whitacre needle PDPH
      risk was 9.6%, and the crude Quincke needle PDPH risk was 15.6%. The absolute
      risk difference was 6.0% with a 95% confidence interval of -0.98% and 13.04%. The
      adjusted Whitacre/PDPH odds ratio was 0.492 with a 95% confidence interval of
      0.241 and 1.003. The Whitacre needle group had a statistically significantly
      lower PDPH severity grade (P = .0151), similar PDPH duration, and more technical
      difficulty with the needle. CONCLUSION: The Whitacre needle is associated with an
      equal or lower PDPH risk; the lack of statistical significance is most likely
      related to sample size. Further study is necessary to determine whether the
      decreased PDPH rate justifies the added difficulty associated with use of the
      Whitacre needle.

PMID- 8756931
TI  - Segmental anatomy of the liver under the right diaphragmatic dome: evaluation
      with axial CT.
AB  - PURPOSE: To evaluate the segmental anatomy of the liver under the right side of
      the diaphragm with axial computed tomography (CT). MATERIALS AND METHODS: Forty
      six patients underwent CT arteriography with selective catheterization of the
      right hepatic artery in 25 cases, the left hepatic artery in 12, the anterior
      branch of the right hepatic artery in six, the posterior branch of the right
      hepatic artery in five, the superior anterior branch of the right hepatic artery
      in 10, and the superior posterior branch of the right hepatic artery in eight.
      RESULTS: The boundary between the right and left lobes shifted by 16.2 degrees +/
      16.8 anteriorly, and the boundary between the anterior and posterior segments
      shifted by 43.9 degrees +/- 14.0 posteriorly to the line through the middle or
      right hepatic vein from the inferior vena cava. The top of the liver consisted of
      both lobes in 22 patients, only the right lobe in 17, and only the left lobe in
      two. Participation of segment 7 in the top was not demonstrated. CONCLUSION: The
      line that extends beyond the middle or right hepatic vein from the inferior vena
      cava does not coincide with the main or right longitudinal scissura on axial
      images of the upper portion of the liver.

PMID- 8756932
TI  - Detection of hepatic metastases: ferumoxides-enhanced MR imaging versus
      unenhanced MR imaging and CT during arterial portography.
AB  - PURPOSE: To prospectively compare the diagnostic accuracy of computed tomography
      (CT) during arterial portography (CTAP) with that of unenhanced and ferumoxides
      enhanced magnetic resonance (MR) imaging at 0.5 T in the detection of hepatic
      metastases. MATERIALS AND METHODS: Four pairs of radiologists independently
      assessed the metastatic involvement of 134 hepatic segments (31 with and 103
      without metastasis) in 17 patients at unenhanced and ferumoxides-enhanced spin
      echo and gradient-echo MR imaging (alone and in combination) and at CTAP. The
      diagnostic performance of the various imaging modalities was assessed by means of
      receiver operating characteristic analysis. RESULTS: The accuracy of CTAP,
      unenhanced MR imaging (combined unenhanced sequences), and ferumoxides-enhanced
      MR imaging (combined contrast material-enhanced sequences) was 0.925, 0.908, and
      0.951, respectively. Ferumoxides-enhanced MR imaging was significantly more
      accurate (P < .05) than unenhanced MR imaging and CTAP. When 14 segments
      containing cysts were excluded, the difference between ferumoxides-enhanced MR
      imaging and CTAP was no longer statistically significant (P = .1). CONCLUSION:
      Ferumoxides-enhanced MR imaging is more accurate than unenhanced MR imaging and
      at least as accurate as CTAP for the detection of hepatic metastases.

PMID- 8756933
TI  - Hepatic artery hemodynamic responsiveness to altered portal blood flow in normal
      and cirrhotic livers.
AB  - PURPOSE: To compare hepatic artery hemodynamic response to altered portal blood
      flow in normal and cirrhotic livers. MATERIALS AND METHODS: The portal blood flow
      and hepatic artery pulsatility index were measured by means of duplex ultrasound
      before and after subjects (eight control subjects and 10 cirrhotic patients)
      ingested a 500-kcal mixed-liquid meal and during intravenous infusion of
      vasopressin at a rate of 0.3 U/min (nine control and nine cirrhotic subjects).
      The hepatic artery buffer index (ratio of maximum change from baseline in hepatic
      artery pulsatility index to maximum change from baseline in portal blood flow)
      was also calculated. RESULTS: Meal consumption increased the portal blood flow
      and hepatic artery pulsatility index in all subjects. The hepatic artery buffer
      index, however, was significantly lower in cirrhotic than in control subjects
      (0.67 min/L +/- 0.06 [standard error of the mean] vs 1.54 min/L +/- 0.20,
      respectively; P < .01). Vasopressin infusion decreased the portal blood flow and
      hepatic artery pulsatility index in all subjects. Again, the hepatic artery
      buffer index was significantly lower in cirrhotic than in control subjects (0.28
      min/L +/- 0.07 vs 0.50 min/L +/- 0.04, respectively; P < .05). CONCLUSION:
      Hepatic artery vascular responsiveness to altered portal blood flow is blunted in
      cirrhotic livers.

PMID- 8756934
TI  - Focal appendicitis confined to the tip: diagnosis at US.
AB  - PURPOSE: To evaluate the diagnostic value of graded-compression ultrasonography
      (US) for the diagnosis of focal appendicitis confined to the tip. MATERIALS AND
      METHODS: During a 4-year period, US was performed in 1,450 patients with
      clinically suspected acute appendicitis. Of these patients, 443 had appendicitis
      at pathologic examination, 20 of whom had focal appendicitis confined to the tip.
      Focal appendicitis confined to the tip was defined as occurring when the resected
      specimen had inflammation only at the distal third of the appendix. RESULTS: Of
      20 patients with focal appendicitis confirmed at pathologic examination, 17
      patients (85%) had focal appendicitis that was correctly diagnosed at US. The
      remaining three patients' appendices were diagnosed at US as normal (false
      negative cases). Five patients had perforation at the tip, and one patient had an
      appendicolith. CONCLUSION: Although US appears to be fairly accurate in the
      diagnosis of focal appendicitis confined to the tip, the entire length of the
      appendix should be evaluated in order to avoid a false-negative diagnosis.

PMID- 8756935
TI  - Subchorionic hemorrhage in first-trimester pregnancies: prediction of pregnancy
      outcome with sonography.
AB  - PURPOSE: To determine the effects of subchorionic hematoma size, gestational age,
      and maternal age on pregnancy outcome in patients with vaginal bleeding in the
      first trimester of pregnancy. MATERIALS AND METHODS: A retrospective review was
      performed with ultrasound images obtained in 516 patients with vaginal bleeding,
      a live fetus, and a subchorionic hematoma in the first trimester. Hematoma size
      was graded according to the percentage of the chorionic sac circumference
      elevated by the hematoma. Patients were also classified according to gestational
      age and maternal age. Logistic regression analysis was used to determine the
      effect of each variable on pregnancy outcome. RESULTS: The overall spontaneous
      abortion rate was 9.3% (48 of 516 patients). The rate nearly doubled when the
      separation was large (18.8%) compared with small and moderate hematomas (7.7% and
      9.2%, respectively). A large separation was found to be associated with an almost
      three-fold increase in risk of spontaneous abortion. The spontaneous abortion
      rate was approximately twice as high for women aged 35 years or older versus
      younger women (13.8% and 7.3%, respectively) and for women with bleeding at 8
      weeks gestation or less compared with those with bleeding at greater than 8 weeks
      gestation (13.7% vs 5.9%). CONCLUSION: For women with a subchorionic hematoma
      that is sonographically identified, fetal outcome is dependent on size of the
      hematoma, maternal age, and gestational age.

PMID- 8756936
TI  - Rib fractures in 31 abused infants: postmortem radiologic-histopathologic study.
AB  - PURPOSE: To examine the morphologic alterations of fractures of the lateral and
      anterior rib arcs and costochondral junction (CCJ) to better understand the
      factors that influence radiographic visualization and to gain insight into the
      mechanism of injury in rib fractures of abused infants. MATERIALS AND METHODS:
      Thirty-one infants (average age, 3 months) who died with inflicted skeletal
      injuries were studied with high-detail, pre- or postmortem skeletal surveys, or
      both, and radiography of specimens, with histologic analysis. The distribution
      and number of fractures were determined for each technique, and dating was
      performed on the basis of radiographic and histologic criteria. The radiologic
      features were correlated with the pathologic findings in comparable histologic
      sections. RESULTS: Of 165 fractures, 84 (51%) involved the ribs. Only 30 rib
      fractures (36%) were visible with skeletal survey examination. Lateral and
      anterior arc fractures tended to impact along the inner cortex of the rib. CCJ
      fractures tended to involve the inner aspect of the osteochondral interface with
      an associated osseous fragment. CONCLUSION: Acute and healing rib fractures are
      common in infants who died with inflicted injury; detection is technique
      dependent. Use of high-detail skeletal radiography to identify these injuries in
      live and deceased infants appears justified.

PMID- 8756937
TI  - Pediatric great vessel anomalies: initial clinical experience with spiral CT
      angiography.
AB  - PURPOSE: To evaluate the use of spiral computed tomographic (CT) angiography for
      the diagnosis of pediatric great vessel anomalies. MATERIALS AND METHODS:
      Techniques used in adult CT angiography were modified to allow imaging of 15
      children aged 1 month to 12 years. Two-dimensional axial images and three
      dimensional shaded surface display images of the airway and great vessels were
      generated from volumetric CT data and evaluated prospectively. Findings were
      correlated with results obtained at surgery (five patients), autopsy (one
      patient), bronchoscopy (one patient), or other imaging studies (eight patients).
      RESULTS: In 14 patients, CT angiography accurately demonstrated vessel anomalies,
      including double or right aortic arch (seven cases), aberrant subclavian artery
      (six cases), innominate artery compression syndrome (one case), unilateral
      pulmonary artery agenesis (one case), and pulmonary artery enlargement (three
      cases). One patient had normal vasculature. CONCLUSION: CT angiography is
      feasible in children and can be used to delineate abnormal great vessel anatomy.

PMID- 8756938
TI  - Performance of radiologic and nuclear medicine examinations in the 6 months
      before death.
AB  - PURPOSE: To determine the rate of use and type of radiologic and nuclear medicine
      examinations performed prior to the death of an individual. MATERIALS AND
      METHODS: Radiologic and nuclear medicine examination data from the University of
      New Mexico Hospital were analyzed and correlated with death records from the New
      Mexico Department of Vital Statistics. The study cohort included 558 patients who
      were treated between July 1992 and June 1993 and died within 6 months. The
      records for the 558 patients were analyzed according to the type and number of
      examinations performed within 30 days and 6 months prior to death. RESULTS: Of
      26,067 patients examined during the year, 558 (2%) underwent a radiographic or
      nuclear medicine examination in the 6 months prior to death. That group of
      patients underwent a total of 6,196 radiographic or nuclear medicine examinations
      (4.6%) out of a total of 134,892 examinations that were performed in that year.
      The rate of use was highest in those patients who were younger than 1 year at
      death. CONCLUSION: Approximately 5% or fewer radiologic and nuclear medicine
      examinations were performed during the final 6 months of an illness.

PMID- 8756939
TI  - Patellar tendinosis (jumper's knee): findings at histopathologic examination, US,
      and MR imaging. Victorian Institute of Sport Tendon Study Group.
AB  - PURPOSE: To determine the histopathologic findings of patellar tendinosis
      ("jumper's knee") demonstrated with ultrasonography (US) and magnetic resonance
      (MR) imaging. MATERIALS AND METHODS: Twenty-four athletes (28 knees) with
      jumper's knee (23 men, one women; mean age, 30.9 years) scheduled to undergo open
      tenotomy underwent US patellar tendon examination. Seventeen patients (19 knees)
      also underwent MR imaging. Tissue was obtained for histopathologic examination in
      all 28 cases. Eleven age-, height-, and weight-matched athletes (22 knees)
      without previous knee symptoms served as control subjects for the US examination.
      Control material for histopathologic examination was obtained in 20 cadavers (39
      knees). Data were analyzed with standard statistical methods. RESULTS: MR imaging
      and US both revealed an abnormal zone at the proximal patellar tendon attachment.
      Histopathologic examination revealed mucoid degeneration in all tendons in
      patients and in 8% (three of 39) of tendons in cadavers (P < .01). CONCLUSION:
      Jumper's knee is characterized by consistent changes at MR imaging, US, and
      histopathologic examination and is appropriately described as patellar
      tendinosis.

PMID- 8756940
TI  - Surgeons' decision making in patients with chronic wrist pain: role of bilateral
      three-compartment wrist arthrography--prospective study.
AB  - PURPOSE: To determine if wrist arthrography changes surgeons' diagnoses and
      treatment plans for patients with chronic wrist pain. MATERIALS AND METHODS:
      Bilateral, three-compartment wrist arthrography was performed in 64 patients.
      Prospective questionnaires evaluated surgeons' diagnoses and management plans at
      three stages: before arthrography, after arthrography of the symptomatic wrist,
      and after arthrography of the asymptomatic wrist. RESULTS: Surgeons tended to
      plan more conservative management after receiving the results of arthrography.
      The number of patients for whom the reported treatment plan included surgery
      dropped from 28 of 64 patients (44%) to 19 of 64 patients (30%) after review of
      the arthrography results (P = .05). The number of patients for whom the treatment
      plan included treatment of any kind dropped from 55 of 64 patients (86%) to 49 of
      64 patients (77%) after review of the arthrography results (P = .09). An overall
      change in treatment plan occurred in 29 of 64 patients (45%). CONCLUSION: Wrist
      arthrography influences surgeons' decision making. After reviewing the results of
      arthrography, surgeons tended to change treatment plans toward more conservative,
      less invasive treatment.

PMID- 8756941
TI  - Peroneus longus and brevis tendon tears: MR imaging evaluation.
AB  - PURPOSE: To evaluate magnetic resonance (MR) findings of surgically proved
      peroneal tendon tears. MATERIALS AND METHODS: MR images, medical records, and
      surgical findings were retrospectively reviewed in the cases of 12 patients who
      underwent surgery because of suspected peroneal tendon tear (14 tendons).
      Sagittal and oblique axial T1-weighted spin-echo and T2-weighted fast spin-echo
      images were obtained in all patients. RESULTS: At surgery, isolated peroneus
      longus tendon tears were seen in four patients, isolated peroneus brevis tendon
      tears in five, and both peroneus brevis and peroneus longus tendon tears in two.
      When correlated with surgical findings, findings at MR imaging were correct in 12
      tendons. Findings were false-positive in two patients and false-negative in one,
      who underwent surgery anyway because unrelated abnormal MR findings were present.
      The most common MR finding was increased intra-substance signal intensity on T1-
      and T2-weighted images (11 tendons), in linear or rounded areas on oblique axial
      images (n = 11) and in linear areas along the longitudinal axis of the tendons on
      sagittal images (n = 7). Tendon distortion was noted in severe cases (five
      tendons). The most frequent surgical finding was a longitudinal tendon tear
      (split) (10 tendons). CONCLUSION: MR imaging enabled detection of peroneus brevis
      and peroneus longus tendon tears.

PMID- 8756942
TI  - Residual-limb shape change: three-dimensional CT scan measurement and depiction
      in vivo.
AB  - PURPOSE: To perform quantitative evaluation of lower-extremity prosthesis fit by
      using spiral computed tomography (CT). MATERIALS AND METHODS: Two spiral CT scans
      were obtained at each of two different sessions in seven adult patients who had
      undergone amputation below the knee. A rigid-body transformation of the tibia was
      computed and used to align paired (intra- and intersession) spiral CT data sets
      for each individual in a common coordinate system. Paired scans in each
      individual were compared to assess registration and precision of soft-tissue
      change measurement. Clinical prosthesis fit evaluation was demonstrated in an
      adult amputee volunteer who underwent CT evaluation while wearing two different
      prostheses. RESULTS: In the seven patients examined, more than 90% of the
      measured soft-tissue volume displacements between sessions could be explained as
      true differences. Precision error of soft-tissue volume change was approximately
      13 cm3, or approximately 1% error relative to the mean volume. Volumetric changes
      due to different prostheses were substantially larger than the random error.
      CONCLUSION: Registration of CT volumetric data sets to quantify residual-limb
      soft-tissue envelope change in lower-limb prosthetics is precise and can be used
      to detect the effect of prosthesis shape alterations.

PMID- 8756943
TI  - Guidance with real-time CT fluoroscopy: early clinical experience.
AB  - A recently developed real-time computed tomography (CT) fluoroscopy system, which
      provides effective real-time reconstruction and display of CT images, was used to
      monitor nonvascular interventional procedures performed in 57 patients. Biopsy of
      thoracic lesions (n = 38), biopsy or drainage of pelvic lesions (n = 6), drainage
      or aspiration of intracranial hematomas (n = 9), and other procedures (n = 4)
      were performed. CT fluoroscopy successfully depicted the entire procedure in all
      patients. In thoracic lesions, a mean 1.3 passes was necessary to gain access to
      the lesion. Sufficient cytologic samples were obtained in 32 of 33 pulmonary
      lesions with a mean diameter of 26 mm.

PMID- 8756944
TI  - Virtual bronchoscopy: segmentation method for real-time display.
AB  - Computed tomography (CT) data sets obtained in 14 patients were used in a
      segmentation method for virtual bronchoscopy (VB). The method constrained the
      distance of propagation of a region-growing algorithm. The resulting three
      dimensional bronchial model was a faithful representation of the source CT data
      and could be manipulated in real time at frame rates of one to two frames per
      second. Preliminary data showed that 90% of bronchi (up to third order)
      measureable on multiplanar CT reformations were also measurable at VB. The
      bronchial diameters measured at VB were within 1 mm of those measured on multi
      planar reconstructions of the CT data.

PMID- 8756945
TI  - Stereotaxic add-on device for MR-guided biopsy of breast lesions.
AB  - Breast biopsy and lesion localization were performed with gadolinium-enhanced
      magnetic resonance (MR) imaging guidance, with use of a stereotaxic biopsy system
      consisting of a flexible circular surface coil with an acrylic cylinder as an add
      on guidance device. Twenty-five procedures (23 localizations, two core biopsies)
      were performed in lesions depicted at diagnostic MR imaging, without technical
      failure. The guidance system permitted easy, precise, and flexible biopsy and
      localization of all breast lesions.

PMID- 8756946
TI  - Optical breast lesion localization fiber: preclinical testing of a new device.
AB  - Preclinical testing was performed of an optical breast lesion localization fiber
      to guide surgical excision. The prototype device comprised dual 0.010- inch
      (0.254-mm)-diameter hooks attached to the tip of a 1,000-microns (0.03937-inch)
      diameter optical fiber, which allowed retention in soft tissue after passage
      through a 17-gauge extra-thin-wall needle. The proximal end of the optical fiber
      was attached to a 15-mW, 635-nm diode laser, with a thumbscrew connector. The tip
      of the optical fiber was visible through several centimeters of breast tissue in
      two human mastectomy specimens, which facilitated determination of the location
      of the hooks. The optical localization fiber may allow lesions to be approached
      at surgery by many different paths. Clinical tests are indicated to further
      evaluate this device.

PMID- 8756947
TI  - Neonatal intracranial ischemia and hemorrhage.

PMID- 8756948
TI  - Power Doppler US in synovitis: reality or artifact?

PMID- 8756949
TI  - Dynamic MR imaging of musculoskeletal neoplasms.

PMID- 8756950
TI  - CT findings of fulminant hepatitis: terminology and distribution of massive
      necrosis.

PMID- 8756951
TI  - Diagnosis of pulmonary embolism.

PMID- 8756952
TI  - "Right" to managed care.

PMID- 8756953
TI  - Perceptual separability, decisional separability, and the identification-speeded
      classification relationship.
AB  - Three observers participated in several sessions of identification and speeded
      classification. Predictions from F. G. Ashby and W. T. Maddox's (1994a) response
      time (RT) theory of speeded classification were tested. A key theoretical concept
      is decisional separability (DS), that is, that the decision about the level of 1
      component does not depend on the perceived value of the other component. The
      theory predicted that DS would hold in the filtering task but would be violated
      in the redundancy task, resulting in the redundancy gains. To summarize the
      results, (a) DS held in the filtering conditions, but not in the redundancy
      conditions; (b) redundancy gains occurred; (c) despite the redundancy gains,
      strong evidence was obtained that the stimulus components are perceptually
      separable; (d) 2 new models that each assumed RT decreases with the distance
      between the percept and the decision bound provided good accounts of the RT
      distributions and accuracy rates; and (e) the shift from identification to
      speeded classification influenced both perceptual and decisional processes.

PMID- 8756954
TI  - Visual control of posture during walking: functional specificity.
AB  - Three experiments examined the functional specificity of visually controlled
      posture during locomotion by presenting large-screen displays to participants
      walking on a treadmill. Displays simulated locomotion down a stationary hallway,
      a hallway that traveled with the observer, or a frontal wall that traveled with
      the observer. A superimposed oscillation specified postural sway in 6 possible
      directions. With the wall, sway amplitude was isotropic and directionally
      specific in all conditions. However, with the hallways, sway was anisotropic
      (lateral > anterior-posterior [AP]), and diagonal responses were flattened into
      the lateral plane. When the treadmill was turned 90 degrees to the hallway, both
      the anisotropy and flattening were reversed (AP > lateral), indicating that they
      are determined by the visual structure of the scene. The results can be explained
      by postural control laws based on both optical expansion and motion parallax,
      yielding biases in planar environments that truncate parallax.

PMID- 8756955
TI  - Conceptual effects on representational momentum.
AB  - Four experiments addressed the question of whether prior knowledge of an object's
      typical movement in the real world affects the representation of motion.
      Representational momentum (RM) is the tendency for the short-term memory
      representation of an object to undergo a transformation corresponding to the
      object's trajectory. Using the standard RM paradigm, the RM elicited by objects
      with different typical motions was compared. Results indicate that conceptual
      knowledge about an object's typical motion affects the magnitude of RM and, as
      such, the representation of motion.

PMID- 8756956
TI  - The relevance of action in perceiving affordances: perception of catchableness of
      fly balls.
AB  - The catchableness of a fly ball depends on whether the catcher can get to the
      ball in time; accurate judgments of catchableness must reflect both spatial and
      temporal aspects. Two experiments examined the perception of catchableness under
      conditions of restricted information pickup. Experiment 1 compared perceptual
      judgments with actual catching and revealed that stationary observers are poor
      perceivers of catchableness, as would be expected by the lack of information
      about running capabilities. In Experiment 2, participants saw the 1st part of
      ball trajectories before their vision was occluded. In 1 condition, they started
      to run (as if to catch the ball) before occlusion; in another, they remained
      stationary. Moving judgments were better than stationary judgments. This supports
      the idea that perceiving affordances that depend on kinematic, rather than merely
      geometric, body characteristics may require the relevant action to be performed.

PMID- 8756957
TI  - Face preference at birth.
AB  - Four experiments are reported that were aimed at elucidating some of the
      controversial issues concerning the preference for facelike patterns in newborns.
      The experiments were devised to contrast the original and the revised versions of
      the sensory hypothesis and the structural hypothesis as accounts of face
      preference in newborns. Experiments 1A and 1B supported the structural hypothesis
      by showing a visual preference for the stimulus for which components were located
      in the correct arrangement for a human face. Experiment 2 supported the sensory
      hypothesis by showing a visual preference for stimuli that were designed to have
      the optimal spatial frequency components for the newborn visual system.
      Experiment 3 showed that babies directed attention to a facelike pattern also
      when it was presented simultaneously with a nonfacelike stimulus with optimal
      spatial frequency for the newborn visual system.

PMID- 8756958
TI  - Inversion and processing of component and spatial-relational information in
      faces.
AB  - This study compared effects of inversion on perceptual processing of faces with
      distorted components (eyes and mouths) and faces distorted by altering spatial
      relations between components. In a rating task, participants inversion reduced
      the rated grotesqueness of spatially distorted faces but not that of faces with
      altered components. In a comparison task, pairs of faces were shown side by side;
      participants judged whether they were identical or different. Inversion greatly
      reduced the rate at which participants responded within 3 s to pairs that
      differed spatially, but not pairs that differed componentially. Also, latencies
      for detecting spatial differences were lengthened by inversion more than
      latencies for detecting componential differences. Results support the hypothesis
      that inversion impairs encoding of spatial-relational information more than, or
      instead of, componential information, depending on the task.

PMID- 8756959
TI  - Configural processing in the perception of apparent biological motion.
AB  - In classic demonstrations of apparent motion, observers typically report seeing
      motion along the shortest possible path between 2 sequentially presented objects.
      However, when realistic photographs of a human body are sequentially presented at
      slow temporal rates, observers report paths of apparent motion that are
      consistent with the movement limitations of the human body even when those paths
      are not the shortest possible. The current set of experiments examined those
      aspects of the human form that lead to the perception of biomechanically
      consistent paths of motion. The authors' findings suggest that the perception of
      apparent biological motion extends to human movements that involve inanimate
      objects. The authors also report that observers can perceive apparent motion of
      nonbiological objects in a manner similar to apparent motion of human bodies.
      However, a global hierarchy of orientation and position cues resembling the human
      form is required for the perception of these paths.

PMID- 8756960
TI  - Perception of local three-dimensional shape.
AB  - The authors present a series of 4 experiments designed to test the ability to
      perceive local shape information. Observers were presented with various smoothly
      varying 3-dimensional surfaces where they reported shape index and sign of
      Gaussian curvature at several probe locations. Results show that observers are
      poor at making judgments based on these local measures, especially when the
      region surrounding the local point is restricted or manipulated to make it
      noncoherent. Shape index judgments required at least 2 degrees of context
      surrounding the probe location, and performance on sign of Gaussian curvature
      judgments deteriorated as the contextual information was restricted as well.

PMID- 8756961
TI  - Detection of smooth three-dimensional surfaces from optic flow.
AB  - An assumption central to the study of 3-dimensional (3-D) shape perception is
      that sufficient information must be present to detect a 3-D surface. Three
      experiments were conducted to determine the variables important for the detection
      of 3-D surfaces from optic flow. Observers were presented with optic-flow
      displays simulating either points positioned on a corrugated 3-D surface or
      points randomly positioned within a 3-D volume. The task of the observer was to
      indicate whether the display appeared to be a 3-D surface. An increase in
      frequency of the corrugation for simple (single-frequency corrugation) surfaces
      resulted in a decrease in surface detection. Detection performance increased with
      an increase in density and amplitude for both simple and complex (multiple
      frequency corrugation) surfaces. An analysis of the deformation of the displays
      suggests that 3-D surface detection may be based on the summed absolute value of
      the 2 shear components of deformation.

PMID- 8756962
TI  - Lexical control of within-word eye movements.
AB  - Eye movements were recorded during the reading of long words, which were
      presented in isolation at their optimal viewing position. Refixations were found
      to be preferentially directed toward the region of the word that contained the
      critical letters for distinguishing it from its competitors. In Experiments 1 and
      2, low-frequency stimulus words sharing all letters except the initial ones with
      a high-frequency stimulus word (critical letters at the beginning of the word)
      elicited more left refixations than low-frequency stimulus words sharing all
      letters except the final ones with a high-frequency stimulus word (critical
      letters at the end of the word). A similar result was found in Experiments 3 and
      4, using an orthographic priming paradigm. These results suggest that refixations
      are linked to the selection stage of lexical access, aimed at isolating a single
      lexical entry among a set of candidates activated during the first fixation.

PMID- 8756963
TI  - The Doppler illusion: the influence of dynamic intensity change on perceived
      pitch.
AB  - Four studies illustrate a new auditory illusion associated with the Doppler
      effect and demonstrate a new influence of dynamic intensity change on perceived
      pitch. Experiment 1 confirmed the existence of a popular belief that the pitch of
      a moving sound source rises as the source approaches. Because there is no
      corresponding rise in frequency, the authors refer to the perceived pitch rise as
      the Doppler illusion. Experiment 2 confirmed that the effect occurs perceptually,
      so the belief in a "naive principle" of physics has a perceptual basis.
      Experiment 3 confirmed the effect does not occur under matched static conditions.
      Experiment 4 showed that the influence of dynamic intensity change on perceived
      pitch occurs outside the realm of Doppler stimuli. The findings support a dynamic
      dimensional interaction of pitch and loudness, with marked differences in the
      perception of pitch and loudness under static and dynamic conditions.

PMID- 8756964
TI  - Effects of lighting on the perception of facial surfaces.
AB  - A series of experiments is reported that investigated the effects of variations
      in lighting and viewpoint on the recognition and matching of facial surfaces. In
      matching tasks, changing lighting reduced performance, as did changing view, but
      changing both did not further reduce performance. There were also differences
      between top and bottom lighting. Recognizing familiar surfaces and matching
      across changes in viewpoint were more accurate when lighting was from above than
      when it was from below the heads, and matching between different directions of
      top lighting was more accurate than between different directions of bottom
      lighting. Top lighting also benefited matching between views of unfamiliar
      objects (amoebae), though this benefit was not found for inverted faces. The
      results are difficult to explain if edge- or image-based representations mediate
      face processing and seem more consistent with an account in which lighting from
      above helps the derivation of 3-dimensional shape.

PMID- 8756965
TI  - Audiovisual links in endogenous covert spatial attention.
AB  - In 7 experiments we investigated cross-modal links for endogenous covert spatial
      orienting in hearing and vision. Participants judged the elevation (up vs. down)
      of auditory or visual targets regardless of their laterality or modality. When
      participants were informed that targets were more likely on 1 side, elevation
      judgments were faster on that side, even if the modality of the target was
      uncertain. When participants expected a target on a particular side in just 1
      modality, corresponding shifts of covert attention also took place in the other
      modality, as evidenced by faster elevation judgments on that side. However, it
      was possible to "split" auditory and visual attention when targets in the 2
      modalities were expected on constant but opposite sides throughout a block,
      although covert orienting effects were larger when targets were expected on the
      same side in both modalities. These results show that although endogenous covert
      attention does not operate exclusively within a supramodal system, there are
      strong spatial links between auditory and visual attention.

PMID- 8756966
TI  - The Dead Sea is alive.

PMID- 8756967
TI  - The Dead Sea as a spa health resort.

PMID- 8756968
TI  - The medical and scientific aspects of spa therapy.

PMID- 8756969
TI  - Dermatology at the Dead Sea spas.
AB  - A background is given to the development of the Dead Sea spas. The treatment and
      results of the therapy for psoriasis, atopic dermatitis and vitiligo are
      outlined, especially for psoriasis. The different factors involved in this spa
      treatment are discussed, and the advantages and disadvantages presented.

PMID- 8756970
TI  - Balneotherapy for rheumatic diseases at the Dead Sea area.
AB  - The Dead Sea region is the major spa area in Israel for patients with various
      types of arthritis. The unique climatic conditions in this area, and the
      balneologic therapy-which is based primarily on mud packs and bathing in sulfur
      baths and in Dead Sea water-combine to alleviate the symptoms of arthritis.
      Controlled studies conducted over the last 10 years have demonstrated that
      treatments provided at the Dead Sea have a positive effect on patients with
      inflammatory arthritides such as rheumatoid and psoriatic arthritis, and on non
      inflammatory arthritides such as osteoarthritis. In addition, the use of mud
      packs and Dead Sea salts dissolved in regular bath water outside the Dead Sea
      region are also effective, although to a lesser degree than when applied at the
      Dead Sea area itself.

PMID- 8756971
TI  - Dead Sea: natural oxygen enrichment at low altitude.
AB  - Patients with advanced chronic obstructive lung disease often require oxygen
      supplementation, which has been shown to increase survival but requires a device
      such as an oxygen tank and tubing. The inspired partial pressure of oxygen
      depends on barometric pressure, which is related directly to altitude. At the
      Dead Sea, located 402 m below sea level, the barometric pressure reaches 800 mm
      Hg, thus resulting in high inspired oxygen levels. We have taken this topographic
      advantage to study oxygen-dependent patients with advanced lung disease. We found
      significant increases in arterial oxygen tension, exercise capacity, sleep oxygen
      saturation, and an improvement in quality of life while staying at the Dead Sea.
      This was found during both a short stay (1 week) as well as a longer stay (3
      weeks). The improvement in exercise capacity persisted 2-3 weeks after leaving
      the area. We conclude that the low altitude at the Dead Sea can be of benefit to
      patients with advanced lung disease who are hypoxemic. The higher the altitude of
      the normal residence of the patient, the greater is the expected benefit of a
      sojourn at the Dead Sea.

PMID- 8756972
TI  - Intercomparison of global, ultraviolet B and A radiation measurements in the Dead
      Sea region (Ein Bokek) and Beer Sheva.
AB  - Thousands of patients suffering from psoriasis have been treated successfully in
      the Dead Sea area by climatological methods, without medication. This high rate
      of success, measured in terms of partial to complete plaque clearance and
      reported to exceed 85% after 3-4 weeks of treatment, has been assumed to be
      associated with a unique ultraviolet (UV) radiation environment present in the
      Dead Sea region. In order to broaden our knowledge of the UV radiation
      environment at the Dead Sea, continuous monitoring of UV (both B and A) and
      global radiation has recently been initiated at two sites--Ein Bokek (located in
      the vicinity of the Dead Sea 375 m below mean sea level) and Beer Sheva (315 m
      above mean sea level)--to facilitate an intercomparison of their respective
      radiation intensities. The results of the first year of a detailed study of the
      global, UVB and UVA radiation intensities measured at both sites are summarized
      and reported in terms of the monthly average daily, average midday (11:00-13:00)
      and the corresponding maximum values. The radiation data for clear days (based
      upon the absolute magnitude of the global radiation) were also analyzed to
      perform an intercomparison between Ein Bokek and Beer Sheva for a winter month
      and a summer month for which all three types of radiation data were available at
      both sites.

PMID- 8756974
TI  - Industrial activity at the Dead Sea.

PMID- 8756973
TI  - Dead Sea mineral-based cosmetics--facts and illusions.
AB  - Modern Dead Sea cosmetics have developed in order to meet the demands of new
      regulations, technical opportunities, and today's consumer expectations for
      higher quality standards and proven performance. As an example of the application
      of this approach, the authors describe the development of a new cosmetic
      formulation, based on "Osmoter", a special Dead Sea mineral composition, and the
      evaluation of this formulation's effect on the depth of skin wrinkles, by a
      controlled assay. Possible mode of action is discussed.

PMID- 8756975
TI  - The Dead Sea in ancient Jewish sources.

PMID- 8756976
TI  - Violence: the scientific medical perspective.

PMID- 8756977
TI  - New devices in interventional cardiology: present and future.
AB  - Interventional cardiology emerged with the development of balloon angioplasty
      some 20 years ago, and has undergone tremendous changes since then. The coronary
      balloon was brought to a mature development stage, being the major "workhorse" of
      interventional cardiology. Various atherectomy techniques, aimed at removing
      plaque material, have been developed and showed immediate beneficial effects on
      the angioplasty results. Laser angioplasty is still looking for an appropriate
      place in interventional cardiology, with most of the results to date being
      disappointing. Stents are emerging as a breakthrough technology which has been
      proven to prevent restenosis and provide an important adjunctive device for
      suboptimal results following balloon angioplasty. Medically coated stents may
      have an important impact on the future of interventional cardiology. Novel
      imaging and flow measurement technologies are being further developed and
      optimized to assist clinical decisions and treatment strategies in interventional
      cardiology. In summary, interventional cardiologists today are provided with a
      set of tools from which they can select the appropriate ones for each lesion
      subset. Together with the appropriate adjunctive pharmaceutical therapy,
      prevention of restenosis is on the horizon.

PMID- 8756978
TI  - Diabetes mellitus is associated with chronic hepatitis C but not chronic
      hepatitis B infection.
AB  - Glucose intolerance is associated with chronic liver disease, particularly
      cirrhosis, and overt diabetes mellitus is two to four times more common than in
      the general population. Little attention has been paid to the relationship
      between the cause of cirrhosis and the development of glucose intolerance or
      whether cirrhosis is a prerequisite. We found glucose intolerance to be
      particularly common in patients with chronic hepatitis C, and in this
      retrospective study we attempt to confirm this possible association. To
      investigate this question we reviewed the files of 128 patients with chronic
      hepatitis C and 40 with chronic hepatitis B and active liver disease.
      Demographic, laboratory, imaging and pathology data were abstracted. The mean
      fasting blood glucose (+/-SD) in the hepatitis C and B groups was 160 +/- 83 and
      103 +/- 18 mg/dl (P < 0.0001) with 2.5% and 39.1% respectively being overtly
      diabetic (P < 0.00001). However, the mean age of the hepatitis C group was much
      higher (45.6 +/- 12.5 vs. 60.1 +/- 12.3 years, P < 0.00001). The prevalence of
      diabetes was much higher among the hepatitis C patients than in the general
      population. Cirrhosis was not more frequent in biopsies from hepatitis C diabetic
      patients compared with non-diabetic or hepatitis B patients. Multivariate
      analysis showed that type of hepatitis and age were significant and independent
      predictors for developing diabetes. We conclude that there appears to be an
      association between diabetes mellitus and chronic hepatitis C that is not present
      in patients with chronic hepatitis B.

PMID- 8756979
TI  - Dynamic parameters of maternal amino acid metabolism and fetal growth.
AB  - This study presents kinetic parameters of glycine metabolism during pregnancy and
      the influence of fuel availability on fetal growth. The kinetic studies were done
      on patients with gestational diabetes mellitus (diet treated) and pre-gestational
      diabetes mellitus (diet and insulin treated) that was accompanied by increased
      fetal growth and pregnancy-induced hypertension and, during the third trimester
      of pregnancy, by intrauterine growth retardation. Gas chromatography-mass
      spectrometry was used to determine the 15N enrichment of plasma glycine, and to
      calculate the pool sizes, turnover rate constants, fluxes and metabolic clearance
      rates. Glycine pool sizes in pre-gestational diabetes were significantly larger
      than those in normal, hypertensive and gestational diabetes pregnancies. Glycine
      turnover rate constants and metabolic clearance rates were not significantly
      different between the normal pregnant women, the hypertensive, and the two
      diabetic groups of pregnant women. Glycine fluxes were significantly higher in
      the pre-gestational diabetic pregnant women than in those with gestational
      diabetes, hypertension, and normal pregnancy. Pre-gestational diabetic pregnant
      women delivered fetuses with higher birthweights than the other three groups.
      Fetal birthweight of the hypertensive women was significantly lower than among
      the normal and diabetic women. Stable isotope methodology using labeled amino
      acids provides a powerful tool for clinical studies of maternal protein
      metabolism and its relationship to fetal growth.

PMID- 8756980
TI  - Anti-topoisomerase-I and clinical findings in systemic sclerosis (scleroderma).
AB  - The relationship between anti-topoisomerase-I antibodies and clinical findings
      was studied in 191 patients with definite systemic sclerosis. This was done by
      performing ELISA to detect antibodies to recombinant topoisomerase-I. Antibodies
      to topoisomerase-I were found in 72 patients (37%) with systemic sclerosis, which
      is a higher percentage than reported in most previous reports on a large
      unselected population. In 43 patients the presence of antibodies to recombinant
      topoisomerase-I was confirmed using both the immunodiffusion method and ELISA,
      with similar results. When classified into diffuse versus limited disease, a
      significant difference in antibody prevalence was demonstrated (P < 0.005), thus
      indicating that anti-topoisomerase-I antibody detection with ELISA may assist in
      early identification of systemic sclerosis subtypes.

PMID- 8756981
TI  - Treatment of subdural empyema by burr hole.
AB  - Subdural empyema, a collection of pus in the space between the dura and
      arachnoid, is a rare type of intracranial infection. We report on 23 patients,
      aged 8 months to 70 years, with subdural empyema who were treated in our clinic
      between 1989 and 1994. The sources of subdural empyemas were meningitis in five
      patients, middle ear in five, trauma in four, paranasal sinus in three,
      complications of surgery and subdural tap in four, and unknown in two patients.
      The common presentations were headache, focal neurologic deficit, fever,
      vomiting, seizures, and neck stiffness. Diagnosis was achieved by computerized
      tomography and neurologic examinations in all cases. Treatment was effected by
      burr hole or small craniotomy with catheter drainage, and antibiotics were
      administered to all patients. The mortality rate was 8.7%; the remaining patients
      made a good recovery without sequelae. We therefore recommend burr hole with
      catheter drainage plus antibiotics as a method of treating subdural empyema.

PMID- 8756982
TI  - Responsibility taking and role definition in family practice: effect of training
      and practice setting.
AB  - There is evidence that family physicians (FPs) reduce health care costs by
      reducing patient referral to more expensive secondary and tertiary care
      facilities. Presumably, the effectiveness of FPs in meeting patients' needs is
      related to their role definition and willingness to assume responsibility. The
      purpose of this study was to determine the influence of training and practice
      setting on responsibility taking and role definition of FPs. A previously
      developed and validated self-administered questionnaire was completed by 153
      certified FPs and FP residents from five departments of family practice in
      Israel. The main independent variables were previous training and practice
      setting. The main outcome measures were self-reported data on responsibility
      taking, role boundaries, and reported role performance. The results showed that
      certified FPs were more willing to assume responsibility, to define broader role
      boundaries, and to perform more specialized interventions than residents.
      Differences in practice setting affected only reported performance, with
      physicians who practice in rural clinics performing more specialized activities
      than those in urban clinics. Multiple regression analysis shows that professional
      development is associated with an increased willingness to assume responsibility;
      this willingness affects role boundaries definitions, which affects reported
      performance. Practice setting alters the tendency to perform a wider range of
      interventions, but does not affect physicians' attitudes.

PMID- 8756983
TI  - Survey of patient satisfaction in a community hospital.
AB  - To assess the satisfaction with the department and hospital services provided by
      a medium-size community hospital during a 2 month period (April-May 1995), 118
      randomly chosen patients were asked to complete a questionnaire designed to
      reflect their opinions during hospitalization. The principal points of the survey
      concerned the general perception regarding the services in the department and the
      hospital, the admission and discharge procedures, the quality of food and
      sanitary conditions, an evaluation of the physicians' and nurses' skill and
      attitude, as well as their compliance to patients' needs. Overall satisfaction
      with the medical care was very high, the physicians' attitude and nurses'
      compliance being the two most important determinants. The role of this type of
      questionnaire as an instrument for improving health services is emphasized.

PMID- 8756984
TI  - Israelis evaluate their health care system.
AB  - This article reports on an analysis of a 1993 evaluation of the Israeli health
      system by a sample of Israeli Jewish urban citizens aged 45-74. Of the population
      sampled 43% thought that only minor changes were needed, 46% stated that
      fundamental changes were needed, and 9% thought that the system should be
      completely revamped. The main users of the system--the elderly--expressed
      somewhat greater satisfaction than did others in the population: 50% thought that
      only minor changes were needed, 42% stated that fundamental changes were needed,
      and 8% thought that the system should be completely revamped. The findings add to
      the growing body of data describing the public's views of health systems in
      several western nations, and can serve, in particular, as a baseline with which
      to compare future evaluations-after the planned changes are implemented.

PMID- 8756985
TI  - Traditional beliefs and disease practices of Ethiopian Jews.
AB  - In an attempt to assess concepts of disease, we questioned 33 Ethiopian Jews
      (Falashas) in Ethiopia about 13 diseases: 8 western and 5 cultural syndromes (in
      the Amharic language): birrd (cold), wugat (stabbing chest pain), moygnbagegn
      (neurologic disorder), mitch (sunstroke), and attent hono kere (retained fetus
      becoming bone). Disease causation was often attributed to spirits and the sun.
      None of the interviewees understood the cause of: a) epilepsy, most attributing
      it to spirits and recommending smelling match smoke as treatment, b) prolonged
      labor, attributed by most to the evil kole spirit and is managed by traditional
      birth attendants; and c) abortion, believed to be caused by exposure to sun or
      cold. Less than 20% linked malaria to mosquitoes. Most correlated splenomegaly
      with malaria. Hepatitis was believed to be caused by a bird or bat flying around
      the affected person. Multiple factors were linked to diarrhea, including a
      journey in the sun. Moygnbagegn is the only condition treated by venisection from
      brachial veins; wugat is treated by "cupping". Modern medicine was recommended by
      < 30% of those questioned for epilepsy, splenomegaly, hepatitis, and Ethiopian
      cultural diseases. It was recommended most for malaria (52%), sexually
      transmitted diseases (55%), and diarrhea (69%).

PMID- 8756986
TI  - Hepatitis C and diabetes mellitus.

PMID- 8756987
TI  - Power and structure in primary care.

PMID- 8756988
TI  - Medical reviews and the importance of being a "peer" in science.

PMID- 8756989
TI  - Ferdinand Ritter von Hebra--founder of modern dermatology.

PMID- 8756990
TI  - Jews and medicine: a temporal overview. Introduction.

PMID- 8756991
TI  - Epidemics in ancient Jewish lore.

PMID- 8756992
TI  - Sarmento, Schomberg and Scotland: Jewish physicians in the period of
      emancipation, 1739-1839.

PMID- 8756993
TI  - History of medicine in the Holy Land during the 19th century, 1842-1914.

PMID- 8756994
TI  - Jewish physicians during the Holocaust.

PMID- 8756995
TI  - Jews and medicine in the USA.

PMID- 8756996
TI  - Death and the dying--treating the hopeless patient.

PMID- 8756997
TI  - The terminally ill--ethical and Jewish perspectives.

PMID- 8756998
TI  - Evaluation of 2-week doctor visit reporting in the national health interview
      survey.
AB  - This report includes a review of previous research on the reporting of ambulatory
      medical visits in household surveys, describes the methods used in the Health
      Interview Evaluation Survey, and presents results relating to the reporting of 2
      week doctor visits.

PMID- 8756999
TI  - Apolipoprotein E and cognitive decline in Alzheimer's disease.

PMID- 8757000
TI  - Spinal cord infarction: etiology and outcome.
AB  - We reviewed 44 cases of ischemia and infarction of the spinal cord at two
      university hospitals. Three patients experienced transient ischemic attacks.
      Etiologies of completed strokes were diverse and included rupture and surgical
      repair of aortic aneurysms, aortic dissection, aortic rupture and thrombosis,
      global ischemia, anterior spinal artery embolism, repair and thrombosis of spinal
      arteriovenous malformations, hematomyelia, epidural hematoma, cervical
      osteophytosis, celiac plexus block, systemic lupus erythematosus, coagulopathy,
      and decompression sickness. Motor function improved in 12 patients, was
      substantial in only one, and occurred largely within the first 2 to 4 weeks.
      Favorable ambulatory outcome correlated with improving neurologic examinations
      and relatively preserved strength in hip abductors and knee extensors. More
      extensive deficits without initial improvement portended a more severe prognosis.
      Autonomic dysfunction, pain, paresthesia, and depression were common and impeded
      recovery in some patients. The mean level of deficit was at T-8 and in cases of
      global ischemia was at T-9, which leads us to dispute the classical view of a
      midthoracic watershed zone of ischemic vulnerability near T-4.

PMID- 8757001
TI  - X-linked malformations of neuronal migration.
AB  - Malformations of neuronal migration such as lissencephaly (agyria-pachygyria
      spectrum) are well-known causes of mental retardation and epilepsy that are often
      genetic. For example, isolated lissencephaly sequence and Miller-Dieker syndrome
      are caused by deletions involving a lissencephaly gene in chromosome 17p13.3,
      while many other malformation syndromes have autosomal recessive inheritance. In
      this paper, we review evidence supporting the existence of two distinct X-linked
      malformations of neuronal migration. X-linked lissencephaly and subcortical band
      heterotopia (XLIS) presents with sporadic or familial mental retardation and
      epilepsy. The brain malformation varies from classical lissencephaly, which is
      observed in males, to subcortical band heterotopia, which is observed primarily
      in females. The XLIS gene is located in chromosome Xq22.3 based on the breakpoint
      of an X-autosomal translocation. Bilateral periventricular nodular heterotopia
      (BPNH) usually presents with sporadic or familial epilepsy with normal
      intelligence, primarily in females, although we have evaluated two boys with BPNH
      and severe mental retardation. The gene for BPNH has been mapped to chromosome
      Xq28 based on linkage studies in multiplex families and observation of a subtle
      structural abnormality in one of the boys with BPNH and severe mental
      retardation.

PMID- 8757002
TI  - Treatment of secondary progressive multiple sclerosis with the immunomodulator
      linomide: a double-blind, placebo-controlled pilot study with monthly magnetic
      resonance imaging evaluation.
AB  - Linomide (quinoline-3-carboxamide) is a synthetic immunomodulator that increases
      the natural killer cell activity. We previously demonstrated that linomide
      effectively inhibited the clinical and histopathologic signs of acute and chronic
      relapsing experimental autoimmune encephalomyelitis. We report a double-blind,
      placebo-controlled study to evaluate tolerability and to obtain preliminary
      indications of the clinical efficacy of linomide on secondary progressive MS.
      Thirty patients suffering from clinically definite and laboratory-supported
      secondary progressive MS, with an expanded disability status scale (EDSS) of 3.0
      to 7.0, were included in this study. Patients were treated daily with linomide
      (2.5 mg) or placebo orally and were followed up for side effects and changes in
      their neurologic status; monthly MRI scans were taken throughout the treatment
      period. Twenty-four patients completed at least 6 months of treatment. Mild to
      moderate side effects, including muscle pains, arthralgia, and edema, were
      present in 11 of the 15 patients receiving placebo and in 13 of the 15 patients
      treated with linomide. At 24 weeks, the mean shift in EDSS was +0.272 +/- 0.156
      in the placebo group versus -0.166 +/- 0.167 in the linomide group (p = 0.0451).
      The percentage of patients with evidence of "activity" on their MRI (new,
      enlarging, or new gadolinium diethylenetriaminepentaacetic acid [Gd-DTPA]
      enhancing lesions) throughout the treatment period was 75% in the placebo group
      and 33% in the linomide group (p = 0.0205). The mean total number of new Gd-DTPA
      enhancing lesions per MRI scan for the same period was 0.42 +/- 0.143 in the
      placebo group and 0.19 +/- 0.114 in the linomide group (p = 0.0387). In this
      study, linomide proved to be safe and well tolerated in patients with secondary
      progressive MS. In addition, our results indicate that linomide tends to inhibit
      the progression of the disease, especially preventing the appearance of new
      active lesions in the MRI scans. Based on these results, two multicenter phase
      III trials are currently under way in the United States and in Europe and
      Australia.

PMID- 8757003
TI  - Clinical concordance in sibling pairs with multiple sclerosis.
AB  - As part of a linkage study, we obtained clinical, demographic, and genetic
      information on 210 families with siblings concordant for multiple sclerosis (MS).
      Twenty-eight pairs were excluded and information was incomplete in a further 16
      pairs; intrafamilial comparisons of the clinical course are reported on the
      remaining 166 families (155 pairs and 11 trios) in whom complete data sets were
      available. The demographic characteristics were comparable to those of recently
      performed prevalence studies in the United Kingdom, supporting the application of
      results in these families for genetic linkage studies in MS. We observed no
      significant correlation for age at onset after correction for selection bias but
      found a minor correlation for year at onset, which we speculate is due to earlier
      recognition of symptoms in second affected siblings. There was no pair-wise
      concordance for presenting symptoms or disability at time of assessment. However,
      there was a strong correlation for disease course and to a lesser degree for
      gender. In addition, the familial recurrence rate was 33%, almost twice that
      previously recorded in a local prevalence study. These results suggest that the
      etiology of MS involves random exposure to an, as yet unidentified, environmental
      trigger and the clinical features of familial disease are modified by inherited
      factors. That the risk of developing MS is not spread uniformly among families
      has important implications for the counseling of individuals with familial
      disease.

PMID- 8757004
TI  - Obsessive-compulsive disorder associated with brain lesions: clinical
      phenomenology, cognitive function, and anatomic correlates.
AB  - We studied the behavioral, cognitive, and neuroimaging characteristics of
      obsessive-compulsive disorder (OCD) in 13 patients with focal brain lesions
      (acquired OCD) and compared their clinical features and the severity of obsessive
      and compulsive (OC) symptoms with patients with idiopathic OCD. Both OCD groups
      were further compared with matched normal controls on a series of
      neuropsychological tests. Patients with acquired OCD had a negative familial
      history and later age at onset of OCD symptoms than patients with idiopathic OCD.
      The two OCD groups showed relatively similar clinical phenomenology, severity of
      OC symptoms, and profile of neuropsychological deficits. Compared with normal
      control subjects, both OCD groups showed cognitive deficits affecting attention,
      intellectual function, memory, word retrieval, and motor and executive functions.
      Eight of the 13 patients with acquired OCD had abnormal neurologic examinations,
      whereas only 3 of the 13 patients with idiopathic OCD had abnormal neurologic
      examinations. Neuroimaging in the acquired OCD group disclosed a variety of
      lesions involving exclusively the cerebral cortex (frontal, temporal, or
      cingulate regions), the basal ganglia, or both. These results suggest that
      acquired and idiopathic OCDs may share a common pathophysiologic mechanism, and
      that structural damage to specific frontal-limbic-subcortical circuits plays an
      important role in the pathogenesis of acquired OCD.

PMID- 8757005
TI  - A comparison of subcutaneous sumatriptan and dihydroergotamine nasal spray in the
      acute treatment of migraine.
AB  - We compared the efficacy and safety of subcutaneous (SC) sumatriptan (6 mg) with
      that of dihydroergotamine (DHE) nasal spray (1 mg plus optional 1 mg) in the
      acute treatment of migraine. Two hundred sixty-six adult migraineurs
      (International Headache Society criteria) completed a multicenter, double-blind,
      double-dummy, cross-over study. Patients took SC sumatriptan for one attack and
      DHE nasal spray for the other in random order. Data from both treatment periods
      show that at all time points from 15 minutes, SC sumatriptan was significantly
      better than DHE nasal spray at providing both headache relief (moderate/severe
      headache improving to mild/none) and resolution of headache. Similarly, SC
      sumatriptan was superior to DHE nasal spray for the other efficacy end points
      assessed in the study. Patients reported that both treatments were well
      tolerated. Adverse events were reported by 43% of patients taking SC sumatriptan
      and 22% of patients taking DHE nasal spray. These were usually mild and
      transient. We conclude that subcutaneous sumatriptan has a faster onset of action
      than DHE nasal spray and provides greater relief of acute migraine symptoms.

PMID- 8757006
TI  - Early CT signs in acute middle cerebral artery infarction: predictive value for
      subsequent infarct locations and outcome.
AB  - During the first hours after acute ischemic stroke, the CT usually shows no
      abnormalities. Therapeutic trials of ischemia in the middle cerebral artery (MCA)
      territory involves decision-making when the CT may not show obvious ischemic
      changes. We reviewed 100 consecutive patients, admitted within 14 hours after a
      first stroke. Selective criteria were clinical presentation with MCA ischemia and
      at least two CTs (1 initial and 1 control). All CTs were retrospectively analyzed
      by at least two physicians blinded to the patient's status. On the first CT,
      early signs were hyperdense MCA sign (HMCAS), early parenchymatous signs
      (attenuation of the lentiform nucleus [ALN], loss of the insular ribbon [LIR],
      and hemispheric sulcus effacement [HSE]), midline shift, and early infarction.
      Subsequent infarct locations were classified according to total, partial
      superficial (superior or inferior), deep, or multiple MCA territories. Clinical
      features, etiology, and Rankin scale were collected. There were 52 women (mean
      age 70.8). The CTs were performed at mean 6.4 hours (1 to 14 hours) and before
      the sixth hour in 62% of the patients. Early CT was abnormal in 94% of the cases,
      and the abnormalities found were an HMCAS in 22 patients, ALN in 48, LIR in 59,
      HSE in 69, midline shift in 5, and early infarct in 7. CT was normal in six
      patients where it was performed earliest (mean 4.5 hours) and in the oldest
      patients (mean age 80.1). Early parenchymatous CT signs were significantly
      associated with subsequent MCA infarct location and extension: ALN and deep
      infarct, HSE and superficial infarct, LIR and large infarct. HMCAS was never
      found in isolation and was always associated with the three other signs in
      extended MCA infarct. The presence of two or three signs (ALN, LIR, or HSE) was
      associated with extended MCA infarct (p < 0.001) and poor outcome (p < 0.001).
      Our findings suggest that CT frequently discloses parenchymal abnormalities
      during the first hours of ischemic stroke. Early signs allow the prediction of
      subsequent infarct locations; CT may provide a simple tool in evaluating the
      early prognosis of MCA infarction and thus may be useful in selecting better
      treatments.

PMID- 8757007
TI  - The stroke syndrome of cortical vein thrombosis.
AB  - Cortical vein thrombosis without sinus involvement is rarely diagnosed, although
      it may commonly be overlooked. We report four cases of cerebral venous thrombosis
      limited to the cortical veins. The diagnosis was made on surgical intervention in
      one patient and by angiography in three patients. Together with a survey of the
      published cases, the clinical and neuroimaging patterns of our patients allow
      delineation of several features suggestive of cortical venous stroke. Focal or
      generalized seizures followed by hemiparesis, aphasia, hemianopia, or other focal
      neurologic dysfunction in the absence of signs of increased intracranial pressure
      should suggest this possibility. Neuroimaging (CT, MRI) shows an ischemic lesion
      that does not follow the boundary of arterial territories and often has a
      hemorrhagic component, without signs of venous sinus thrombosis. Conventional
      angiography demonstrates no arterial occlusion but may show cortical vein
      thrombosis corresponding to the infarct, although these may also be nonspecific
      findings. The role of MR angiography, which is well-established in sinus
      thrombosis, remains to be assessed in patients with brain ischemia due to
      isolated cortical vein occlusion.

PMID- 8757008
TI  - Factors delaying hospital admission in acute stroke: the Copenhagen Stroke Study.
AB  - Medical treatment of stroke is dependent on a narrow therapeutic time window. We
      prospectively analyzed the influence of demographic, medical, and
      pathophysiologic factors on admission delay in 1,197 unselected, acute stroke
      patients. Twenty five percent were admitted within 3 1/2 hours, 35% within 6
      hours, 50% within 14 hours, and 68% within 24 hours after stroke onset. Living
      alone (odds ratio [OR] 1.75, 95% CI 1.3 to 2.3) and retired working status (OR
      1.61, 95% CI 1.01 to 2.54) delayed admission. A well-working social network thus
      seems important to early admission. The milder the stroke, the higher was the
      risk of delayed admission (OR 1.25 per 10 points decrease in stroke severity
      [Scandinavian Neurological Stroke Scale score on admission], 95% CI 1.14 to
      1.36). A history of TIA increased the relative chance of early admission by odds
      1.64 (95% CI 1.06 to 2.54). Other factors such as age, sex, diabetes,
      hypertension, ischemic heart disease, other comorbidity, previous stroke,
      headache, aphasia, apraxia, anosognosia, neglect, lowered consciousness, mental
      status (Mini-Mental State Examination) and type of stroke (hemorrhage/infarct)
      had no independent influence on admission time. Admission was markedly delayed in
      most patients. This represents a major barrier to medical treatment. Patients
      with the most severe strokes are admitted early, but patients with milder
      symptoms should also be encouraged to seek immediate admission. The observation
      that a history of TIA reduced admission time indicates that an increase in public
      awareness and knowledge may reduce delay and save precious time.

PMID- 8757009
TI  - Factors predictive of stroke outcome in a rehabilitation setting.
AB  - Accurate outcome prediction following stroke is important for proper delivery of
      poststroke care. It has been difficult to determine specific factors that provide
      reliable and accurate predictions of outcome, particularly for patients with
      intermediate deficit severities. Age and severity of deficit have repeatedly been
      found to be most reliable, but only as rough estimates and for patients at either
      extreme of the disability spectrum. This paper reports a prospective study of
      consecutive rehabilitation admissions (N = 536) to determine the influence of
      preselected factors. Outcome was analyzed in terms of functional improvement and
      disposition. Patients younger than 55 years or with an admission Functional
      Independence Measure (FIM) greater than 80 almost universally went home.
      Admission FIMs less than 40 were associated with nearly certain nursing home
      discharge. The comprehensive FIM score was a stronger predictor of outcome than
      motor impairment in isolation. An admission FIM of 60 or greater was associated
      with a higher probability of functional improvement during rehabilitation. Small
      vessel strokes had the best outcome. Intracerebral hemorrhages improved more than
      ischemic strokes but more slowly. Right hemisphere lesions did worse than left.
      Comorbidities influenced outcome only when several conditions accumulated. The
      absence of a committed caregiver at home increased the risk of nursing home
      discharge. Suggestions for rehabilitation triage are given.

PMID- 8757010
TI  - The value of intracranial pressure monitoring in acute hemispheric stroke.
AB  - BACKGROUND AND PURPOSE: Persistently elevated intracranial pressure (ICP) has
      been associated with poor clinical outcome after severe brain injury, such as
      neurotrauma, intracerebral hemorrhage, and subarachnoidal hemorrhage. Although
      ICP monitoring is increasingly being used in intensive care treatment of patients
      with ischemic stroke, its value has not been established. PATIENTS AND METHODS:
      The clinical course of 48 patients with the clinical signs of increased ICP due
      to large hemispheric or middle cerebral artery territory infarction defined by CT
      and subjected to ICP monitoring was prospectively evaluated. Epidural ICP probes
      were inserted ipsilaterally to the site of primary brain injury in all and also
      contralaterally in seven patients. Initial clinical presentation was assessed by
      the Scandinavian Stroke Scale (SSS) and the Glasgow Coma Score (GCS). All
      patients were treated according to a standardized treatment protocol for elevated
      ICP. ICP values were correlated with the clinical presentation at the time point
      of deterioration, with outcome, and with CT findings. Different treatment
      strategies to lower ICP were analyzed as to their effectiveness. RESULTS: Only
      nine of the 48 patients survived the infarct (19%). The cause of death was
      transtentorial herniation with subsequent brain death in all 39 patients. The
      patients' mean SSS on admission was 20.6 (survivors 21.5 +/- 5.6, nonsurvivors
      19.8 +/- 6.5). In all patients clinical signs of herniation preceded the increase
      in ICP. Patients with ICP values > 35 mm Hg did not survive. CT changes did not
      always correspond with the measured ICP values. All medical strategies to lower
      ICP, including osmotherapy, hyperventilation, THAM-buffer, and barbiturates, were
      initially effective, but only in a minority of patients was ICP control
      sustained. CONCLUSIONS: ICP monitoring of large hemispheric infarction can
      predict clinical outcome. Pharmacologic intervention had no sustained effect. ICP
      monitoring was not helpful in guiding long-term treatment of increased ICP. It
      remains doubtful that ICP monitoring in acute ischemic stroke has a positive
      influence on clinical outcome.

PMID- 8757011
TI  - Cerebral metabolic differences between the severe and critical hypoperfused
      brain.
AB  - Occlusion or severe stenosis, with a reduction in the diameter of the
      extracranial arteries of more than 70%, may lead to hypoperfusion of the brain
      with an increased risk of cerebral infarction. The aim of this study was to
      investigate whether a decrease in metabolism in noninfarcted hypoperfused
      cerebral areas is correlated with the level of hypoperfusion. Fifty-one patients
      without infarcts, with borderzone infarcts, with territory infarcts, and fourteen
      healthy control subjects were investigated with MRI and MR spectroscopic imaging.
      The NAA/choline ratio in the symptomatic hermisphere was significantly decreased
      in patients with borderzone infarcts compared with patients without infarcts,
      with patients with territory infarcts, and with control subjects. Furthermore,
      patients with borderzone infarcts had a relatively high frequency of cerebral
      lactate. These results indicate that there might be a lower limit of
      hypoperfusion that can be measured indirectly with MR spectroscopic imaging,
      below which irreversible cerebral damage occurs.

PMID- 8757012
TI  - Incidence of spontaneous intracerebral hemorrhage among Hispanics and non
      Hispanic whites in New Mexico.
AB  - OBJECTIVE: To compare the incidence of spontaneous intracerebral hemorrhage (ICH)
      among Hispanics and non-Hispanic whites living in Bernalillo County, NM.
      BACKGROUND: There are differences in cerebrovascular disease incidence between
      racial and ethnic groups. Knowing these differences is likely to optimize stroke
      prevention and evaluation. METHODS: Medical records review of all possible cases
      of ICH occurring between January 1, 1993 and December 31, 1993 among residents of
      Bernalillo County, NM, in all local hospitals. Hospital records were identified
      by ICD-9-CM codes. Also, State Medical Examiner records review for additional ICH
      cases occurring during the same time interval. The 1990 U.S. census provided the
      population base. RESULTS: There were 47 spontaneous ICHs among 267,965 non
      Hispanic whites and 39 spontaneous ICHs among 178,310 Hispanics. Incidence of ICH
      rises exponentially with age in both groups. The age- and sex-adjusted total
      annual incidence of ICH per 100,000 people is 16.6 among non-Hispanic whites and
      34.9 among Hispanics (relative risk for Hispanics 2.10, 95% confidence interval
      1.35 to 3.26, p = 0.001). The age-adjusted incidence rates among men and women
      are not significantly different in either ethnic group. CONCLUSION: The incidence
      of spontaneous ICH among Hispanic residents of Bernalillo County, NM, is
      approximately twice that among non-Hispanic whites. The reasons for this
      difference require further investigation.

PMID- 8757013
TI  - Positive spontaneous visual phenomena limited to the hemianopic field in lesions
      of central visual pathways.
AB  - We prospectively studied 32 patients with ischemic infarction of the
      retrochiasmal visual pathways. Positive spontaneous visual phenomena (PSVP) in
      the blind hemifield were present in 13 patients (41%). The PSVP were subdivided
      into phosphenes, photopsias, visual hallucinations, palinopsia, and agitated
      delirium with hemianopia. PSVP were never associated with auditory or other
      sensory positive phenomena, except in patients with agitated delirium. Patients
      with photopsias, phosphenes, palinopsia, and visual hallucinations had similar
      lesions in MRI/CT, suggesting no anatomic area unique for these four phenomena.
      However, there was a significant difference in the severity of associated
      neurologic deficits between hemianopic patients with and without PSVP. Larger
      lesions destroying anteriorly located visual association areas precluded the
      development of PSVP, which may be related to release from inhibitory input of
      visual regions bordering the damaged area. Patients with the syndrome of agitated
      delirium and hemianopia had specific lesions involving the mesial aspect of the
      occipital lobe, the parahippocampal gyrus, and hippocampus.

PMID- 8757014
TI  - Multiple cerebral lesions complicating therapy with interleukin-2.
AB  - We reviewed the records and radiologic studies of eight patients who developed
      new focal neurologic abnormalities while receiving interleukin-2 (IL2)-based
      immunotherapy for malignancy or HIV infection. Initial confusion and delirium in
      the patients evolved into coma, ataxia, hemiparesis, seizures, and cortical
      syndromes including aphasia, apraxia, and cortical blindness. Imaging studies
      showed multiple white and gray matter lesions with a predilection for the
      occipital poles, centrum semiovale, and cerebellum. After cessation of IL2
      treatment, seven patients improved to normal or near-normal neurologic function
      paralleled by resolution of the lesions on scans. One patient improved only
      minimally. Possible etiologies for the lesions include an IL2-induced cerebral
      vasculopathy, a direct toxic effect of IL2, or immunologically mediated damage.

PMID- 8757015
TI  - Arthritis and anti-inflammatory agents as possible protective factors for
      Alzheimer's disease: a review of 17 epidemiologic studies.
AB  - Alzheimer's disease (AD) lesions are characterized by the presence of numerous
      inflammatory proteins. This has led to the hypothesis that brain inflammation is
      a cause of neuronal injury in AD and that anti-inflammatory drugs may act as
      protective agents. Seventeen epidemiologic studies from nine different countries
      have now been published in which arthritis, a major indication for the use of
      anti-inflammatory drugs, or anti-inflammatory drugs themselves have been
      considered as risk factors for AD. Both factors appear to be associated with a
      reduced prevalence of AD. The small size of most studies has limited their
      individual statistical significance, but similarities in design have made it
      possible to evaluate combined results. We have used established methods of
      statistical meta-analysis to estimate the overall chance of individuals exposed
      to arthritis or anti-inflammatory drugs developing AD as compared with the
      general population. Seven case-control studies with arthritis as the risk factor
      yielded an overall odds ratio of 0.556 (p < 0.0001), while four case-control
      studies with steroids yielded odds ratios of 0.656 (p = 0.049) and three case
      control studies with nonsteroidal anti-inflammatory drugs (NSAIDs) yielded an
      odds ratio of 0.496 (p = 0.0002). When NSAIDs and steroids were combined into a
      single category of anti-inflammatory drugs, the odds ratio was 0.556 (p <
      0.0001). Population-based studies were less similar in design than case-control
      studies, complicating the process of applying statistical meta-analytical
      techniques. Nevertheless, population-based studies with rheumatoid arthritis and
      NSAID use as risk factors strongly supported the results of case-control studies.
      These data suggest anti-inflammatory drugs may have a protective effect against
      AD. Controlled clinical trials will be necessary to test this possibility.

PMID- 8757016
TI  - Predictors of mortality in patients diagnosed with probable Alzheimer's disease.
AB  - OBJECTIVE: We sought to identify factors associated with mortality in persons
      recently diagnosed with probable Alzheimer's disease (AD). BACKGROUND: Predicting
      mortality in AD in needed both in patient care and public health planning.
      Previous studies have identified several factors which contribute to mortality in
      AD, but few longitudinal studies of population-based cohorts exist. METHODS: In a
      longitudinal follow-up study 327 patients with newly diagnosed probable AD (mean
      Mini-Mental State Examination [MMSE] score of 20) from a large, stable health
      maintenance organization were identified. Demographic characteristics, dementia
      severity, and comorbid conditions were identified at enrollment. Patients were
      followed longitudinally (median 3.3 years, total 898 person-years). Baseline
      characteristics were used to predict survival in univariate and multivariate
      models. RESULTS: Increased mortality was seen in patients with probable AD (9.0
      deaths per 100 person-years) compared with the community population adjusted for
      age and gender (4.3 deaths per 100 person-years). On univariate analysis we found
      increased age, male gender, impairment on MMSE or Blessed dementia rating scale
      (DRS), rate of MMSE decline, wandering or agitation, vascular disease, and
      sensory impairment affecting the ability to read or hear to be moderately
      associated with decreased survival. After adjusting for age and gender in a
      multivariate model, Blessed DRS score and sensory impairment affecting the
      ability to read were independently associated with decreased survival.
      CONCLUSIONS: Short-term mortality is increased in patients newly diagnosed with
      probable AD. Measures of dementia severity, measures of general debility, and
      vascular disease are associated with increased mortality. Of these, general
      debility and sensory impairment were more strongly associated with shortened
      survival.

PMID- 8757017
TI  - Apolipoprotein E epsilon 4 allele, cognitive decline, and deterioration of
      everyday performance in Alzheimer's disease.
AB  - Many studies have demonstrated an association between the apolipoprotein E (apoE)
      epsilon 4 allele and Alzheimer's disease (AD). The present study is concerned
      with the relationship between the apoE epsilon 4 allele and the progression of
      symptoms in AD. We determined rates of cognitive decline and deterioration in
      everyday performance prospectively over 3 years in 64 patients with clinically
      diagnosed AD using the Cambridge Cognitive Examination (CAMCOG), the Mini-Mental
      State Examination (MMSE), and the Dementia Scale (DS) included in the Cambridge
      Mental Disorders of the Elderly Examination (CAMDEX). Carriers and noncarriers of
      the epsilon 4 allele did not significantly differ in cognitive functioning and
      everyday performance at baseline measurements. The time that had elapsed since
      the estimated onset of symptoms was also not different between the two groups.
      This suggested that the clinical progression of AD was not associated with the
      epsilon 4 status before the patients entered the study. On prospective
      observation, the rate of cognitive decline assessed with the CAMCOG and the MMSE
      and the rate of deterioration in everyday performance rated with the DS were also
      not different between carriers and noncarriers of the epsilon 4 allele. We
      conclude that the clinical course of AD is independent of the apoE epsilon 4
      allele.

PMID- 8757018
TI  - Apolipoprotein E genotype does not influence rates of cognitive decline in
      Alzheimer's disease.
AB  - BACKGROUND: Inheritance of the apolipoprotein E (apoE) epsilon 4 allele is a risk
      factor for developing Alzheimer's disease (AD) and is associated with a lower age
      of dementia onset. The purpose of this study was to determine whether apoE
      genotypes differentially influence the course of cognitive decline in AD
      dementia. METHODS: We administered nine cognitive tests that assessed explicit
      memory, attention, language, visuospatial function, frontal-lobe function, and
      logical reasoning abilities to 66 probable AD patients every 6 to 24 months over
      a span of up to 5.5 years. We identified apoE genotype by a PCR-based method;
      there were 16 patients with epsilon 3/3, 34 with epsilon 3/4, and 16 with epsilon
      4/4. Using regression statistical methods, we computed the change in performance
      for each test for each patient over time. We then analyzed the mean change in
      each test in patients grouped according to apoE genotype. RESULTS: For the AD
      patients as a group, performance on all cognitive tests declined significantly
      over time, but the rate of decline did not vary significantly across apoE
      genotypes on any cognitive test. Specifically, the rate of cognitive decline was
      not faster in patients with an epsilon 4 allele than in those with epsilon 3/3.
      CONCLUSIONS: These results indicate that the mechanism placing individuals with
      an epsilon 4 allele at risk for developing AD does not influence the rate of
      cognitive decline. These observations imply that the influence of apoE epsilon 4
      either precedes or occurs at an early point in the AD disease process.

PMID- 8757019
TI  - Scrapie in mice deficient in apolipoprotein E or glial fibrillary acidic protein.
AB  - In the prion diseases, extensive reactive gliosis is often found to be out of
      proportion to the degree of apparent neuronal damage. To evaluate the role of
      astrocytic gliosis in experimental scrapie of the mouse, we inoculated mice
      deficient in apolipoprotein E (apoE) or the glial fibrillary acidic protein
      (GFAP) with mouse prions. The expression of both apoE and GFAP in astrocytes
      increases as part of the reactive gliosis that accompanies scrapie. Null mice
      deficient in either apoE or GFAP inoculated with prions exhibited incubation
      times indistinguishable from untargeted control mice. The level of PrPSc and its
      regional deposition in the brains of ill mice deficient in either protein were
      also similar to control mice. Our findings demonstrate that neither apoE nor GFAP
      participates in the pathogenesis of the disease or in the production of PrPSc.

PMID- 8757020
TI  - Regional hypometabolism in Alzheimer's disease as measured by positron emission
      tomography after correction for effects of partial volume averaging.
AB  - Measurements of cerebral metabolism in patients with Alzheimer's disease (AD)
      using PET are artifactually depressed due to partial volume averaging of brain
      tissue activity with enlarged CSF spaces. To investigate the effects of
      correction for the expansion of CSF spaces on regional metabolic measures, as
      well as the correlations between neuropsychological test results and resting
      cerebral metabolism before and after partial volume correction, we applied an MRI
      based method of partial volume correction to 18F-fluorodeoxyglucose (FDG)-PET
      data from eight patients diagnosed with probable AD and ten healthy elderly
      individuals. Before correction, the AD group had significantly lower cortex-to
      cerebellum ratios in the posterior temporal, parietal, and frontal lobes in
      comparison to the control subjects. Partial volume correction of PET data
      resulted in 19 to 49% increases in regional activity in the AD group and 16 to
      38% increases in the control group. The patients' persistence of significant
      hypometabolism in the frontal, posterior temporal, and parietal regions after
      partial volume correction suggests that a true reduction in regional cerebral
      glucose metabolism occurs in AD, even though its magnitude is a result of both
      metabolic reductions and the effects of atrophy. Partial volume correction of PET
      data in the AD group had a significant impact on the correlations between
      regional glucose metabolism and neuropsychological performance. These findings
      suggest that accounting for differential extent and distribution of cerebral
      atrophy in patients with AD and in healthy individuals may potentially improve
      our ability to interpret specific cognitive dysfunction in the context of the
      functional imaging data.

PMID- 8757021
TI  - Fluoro-deoxyglucose positron emission tomography in diffuse Lewy body disease.
AB  - We report six demented individuals with pathologically verified diffuse Lewy body
      disease (DLBD) studied with fluoro-deoxyglucose positron emission tomography (FDG
      PET). Three subjects had pure DLBD and three subjects had combined DLBD and
      Alzheimer's disease (DLBD-AD) pathology. FDG-PET revealed evidence of diffuse
      cerebral hypometabolism in both pure DLBD and DLBD-AD with marked declines in
      association cortices with relative sparing of subcortical structures and primary
      somatomotor cortex, a pattern reported previously in AD. Unlike AD, however,
      these subjects also had hypometabolism in the occipital association cortex and
      primary visual cortex. These findings indicate the presence of diffuse cortical
      abnormalities in DLBD and suggest that FDG-PET may be useful in discriminating
      DLBD from AD antemortem.

PMID- 8757022
TI  - Primary progressive apraxia in Pick's disease: a clinicopathologic study.
AB  - A 62-year-old right-handed man gradually experienced increasing difficulty with
      speech and manual dexterity. He had apraxia of speech, buccofacial apraxia, and
      complex limb apraxia as well as terminal dementia. At autopsy, focal cortical
      atrophy, neuronal loss, and neuropil rarefaction in the second and third cortical
      layers were most prominent in the left opercular, lower precentral, superior
      parietal, and left temporal pole. Numerous Pick bodies were diffusely present in
      the temporal and posterior frontal lobes and, to a lesser degree, in the superior
      parietal lobule. This report demonstrates an association between the distribution
      of Pick's pathology and several apraxic impairments.

PMID- 8757023
TI  - Reversible dementia in idiopathic hypoparathyroidism associated with
      normocalcemia.
AB  - Dementia in idiopathic hypoparathyroidism is generally ascribed to hypocalcemia
      and improves following normalization of the serum calcium level. We report a 51
      year-old man with severe dementia and hypoparathyroidism, but without serum
      hypocalcemia and without clinical signs of hypocalcemia. There was rapid and
      sustained improvement and normalization of symptoms after therapy with 1,25
      dihydroxy-cholecalciferol. We conclude that hypocalcemia is not the sole cause of
      dementia in idiopathic hypoparathyroidism.

PMID- 8757024
TI  - Corpus callosum morphology in children with Tourette syndrome and attention
      deficit hyperactivity disorder.
AB  - The aim of this study was to investigate the morphology of the corpus callosum
      (CC) in Tourette syndrome (TS) and attention deficit hyperactivity disorder
      (ADHD) to determine whether these conditions affect distinct regional
      differences. Seventy-seven children and adolescents, aged 6 to 16 years,
      comprised the four research groups--16 patients with TS, 21 patients with TS plus
      ADHD, 13 patients with ADHD, and 27 unaffected control subjects. A semiautomated,
      computer-assisted procedure was used to measure the total area, five subregions,
      centerline length, perimeter, and bending angle of the CC. MRI data were analyzed
      using several statistical methods, primarily two-tailed analysis of variance to
      test the effects of TS and ADHD status, while controlling for the influence of
      age, gender, and total intracranial area (an estimate of brain size). TS was
      associated with significant increases in the area of four of five subdivisions,
      the total area, and the perimeter of the CC. ADHD was associated with a
      significant decrease in the area of the rostral body. There were no interactions
      between TS and ADHD factors. These findings suggest that the area of the CC is
      larger in children with TS, and that this difference is independent of age,
      handedness, intracranial area, and the diagnosis of ADHD. Our findings support
      hypotheses that the neurobiologic mechanisms in TS and ADHD involve
      frontal/subcortical circuits.

PMID- 8757025
TI  - Contralesionally beating torsional nystagmus in a unilateral rostral midbrain
      lesion.
AB  - The rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF)
      and the interstitial nucleus of Cajal (iC) are involved in the generation of
      vertical and torsional saccades and gaze holding. Midbrain lesions involving
      either riMLF or iC produce a tonic torsional ocular deviation to the
      contralesional side. Lesions of the iC are associated with an ipsilesional
      torsional nystagmus (TN). For the first time, we describe a patient with a
      unilateral midbrain lesion showing a contralesionally beating torsional
      nystagmus. This nystagmus was probably caused by a lesion involving the riMLF.

PMID- 8757026
TI  - Headache in ambulatory HIV-1-infected men enrolled in a longitudinal study.
AB  - OBJECTIVE: To report headache (HA) data collected from subjects in a longitudinal
      study of human immunodeficiency virus (HIV)-1 and the central nervous system
      (CNS) DESIGN/METHODS: Baseline data from 229 ambulatory HIV-seropositive (HIV+)
      and 53 seronegative control subjects were analyzed. Subjects were classified by
      the presence or absence of HIV-1-associated HAs and HIV-1-associated systemic and
      neurologic disease. Subjects were followed longitudinally for up to 5 years.
      RESULTS: In the cross-sectional analysis, significant associations were observed
      between HIV-1-associated HAs and (1) anxiety and depression, and (2) a history of
      drug use, psychiatric disease, and non-HIV-1 neurologic disease. No significant
      differences in laboratory values were found between subjects with HIV-1
      associated HA compared with those without HA. When HIV+ subjects were followed
      longitudinally, onset of new HIV-1-associated systemic or neurologic disease over
      1 year was not predicted by the presence of an HIV-1-associated HA at baseline.
      CONCLUSION: Headaches are common in HIV+ persons at all stages of disease.
      Presence of HIV-1-associated HAs at baseline were not associated with neurologic
      disease progression over 1 year of follow-up in our sample.

PMID- 8757027
TI  - Headache in intracerebral hematomas.
AB  - OBJECTIVES: We sought to describe the frequency and location of headache in
      intracerebral hematoma (ICH) and to analyze its clinical and CT predictors by
      means of multivariate analysis. BACKGROUND: Headache is more common in
      intracerebral hemorrhage than in ischemic stroke, and its frequency varies with
      hematoma location, but the pathophysiologic mechanisms of headache associated
      with ICH are not fully known. METHODS: We examined a cohort of 289 patients with
      ICH during a 14-month period in a university hospital. Clinical, including the
      presence and location of headache, and CT features were collected by two
      neurologists. RESULTS: One hundred and sixty-five (57%) patients with ICH had a
      headache at the onset of their stroke. Headache was more common in cerebellar and
      lobar hemorrhages than in deep ones (thalamic, caudate, capsuloputaminal,
      brainstem). Headache was also more common in women, patients younger than 70
      years, those who vomited, and those with meningeal signs, a Glasgow Coma Scale
      score < 10, a hematoma volume > 10 ml or CT evidence of intraventricular or
      subarachnoid bleeding, moderate to severe hydrocephalus, or transtentorial
      herniation or midline shift. In multiple logistic regression analysis, only
      meningeal signs (odds ratio [OR] = 2.3), cerebellar or lobar location (OR = 2.1),
      transtentorial herniation (OR = 1.8), and female gender (OR = 1.6) were
      significant predictors of headache at the onset of ICH. CONCLUSIONS: Hematoma
      location, meningeal signs, and gender are more predictive of headache than
      hematoma volume, suggesting that headache is more often related to the activation
      of an anatomically distributed system in susceptible individuals and to
      subarachnoid bleeding than to intracranial hypertension.

PMID- 8757028
TI  - Diurnal systolic blood pressure variability is the strongest predictor of early
      carotid atherosclerosis.
AB  - We studied the relationship between circadian blood pressure changes and
      development of early carotid atherosclerosis in 208 hypertensive and 216
      normotensive patients older than age 55 years. Blood pressure patterns were
      evaluated noninvasively with a long-term blood pressure monitor, and extent of
      atherosclerosis was measured as the intima to media wall thickness (IMT) of the
      common carotid artery. No significant differences regarding age, sex, smoking,
      diabetes, cholesterol, and triglycerides were found between both patient groups.
      The age-adjusted IMT was significantly larger in the hypertensive patients (1.34
      mm [95% confidence interval 1.24, 1.44] versus 1.18 mm [1.14, 1.22]; p < 0.05).
      However, after adjustment for diurnal systolic blood pressure variability, which
      was significantly increased in the hypertensive group, the significant IMT
      difference between both patient groups was no longer observed (1.32 mm [1.27,
      1.37] versus 1.29 mm [1.25, 1.33]). Multivariate regression analysis revealed the
      diurnal systolic blood pressure variability as the strongest predictor for IMT.
      The IMT was most increased in hypertensive patients with increased diurnal
      systolic blood pressure variability and additional nocturnal blood pressure
      increase (1.64 mm [1.45, 1.83]. The odds ratio of having early atherosclerosis
      (age-adjusted IMT > 1.5 mm) increased with raised diurnal systolic blood pressure
      variability (> 15 mm Hg) in both groups (normotensive: 8.5 [2.30]; hypertensive:
      12.6 [4, 43]). The diurnal systolic blood pressure variability is the strongest
      predictor of early carotid atherosclerosis measured with B-mode ultrasonography
      and is useful to define the risk-benefit ratio of therapeutic approaches,
      particularly in patients with only slightly elevated blood pressure levels.

PMID- 8757029
TI  - A primate genesis model of focal dystonia and repetitive strain injury: I.
      Learning-induced dedifferentiation of the representation of the hand in the
      primary somatosensory cortex in adult monkeys.
AB  - In this study we tested a neuroplasticity/learning origins hypothesis for
      repetitive strain injuries (RSIs), including occupationally induced focal
      dystonia. Repetitive movements produced in a specific form and in an appropriate
      behavioral context cause a degradation of the sensory feedback information
      controlling fine motor movements, resulting in the "learned" genesis of RSIs. Two
      adult New World owl monkeys were trained at a behavioral task that required them
      to maintain an attended grasp on a hand grip that repetitively and rapidly (20
      msec) opened and closed over short distances. The monkeys completed 300
      behavioral trials per day (1,100 to 3,000 movement events) with an accuracy of 80
      to 90%. A movement control disorder was recorded in both monkeys. Training was
      continued until the performance accuracy dropped to below 50%. We subsequently
      conducted an electrophysiologic mapping study of the representations of the hand
      within the primary somatosensory (SI) cortical zone. The hand representation in
      the true primary somatosensory cortical field, SI area 3b, was found to be
      markedly degraded in these monkeys, as characterized by (1) a dedifferentiation
      of cortical representations of the skin of the hand manifested by receptive
      fields that were 10 to 20 times larger than normal, (2) the emergence of many
      receptive fields that covered the entire glabrous surface of individual digits or
      that extended across the surfaces of two or more digits, (3) a breakdown of the
      normally sharply segregated area 3b representations of volar glabrous and dorsal
      hairy skin of the hand, and (4) a breakdown of the local shifted-overlap
      receptive field topography of area 3b, with many digital receptive fields
      overlapping the fields of neurons sampled in cortical penetrations up to more
      than four times farther apart than normal. Thus, rapid, repetitive, highly
      stereotypic movements applied in a learning context can actively degrade cortical
      representations of sensory information guiding fine motor hand movements. This
      cortical plasticity/learning-based dedifferentiation of sensory feedback
      information from the hand contributes to the genesis of occupationally derived
      repetitive strain injuries, including focal dystonia of the hand. Successful
      treatment of patients with RSI will plausibly require learning-based restoration
      of differentiated representations of sensory feedback information from the hand.

PMID- 8757030
TI  - A longitudinal study of multimodal evoked potentials in patients following
      radiotherapy for nasopharyngeal carcinoma.
AB  - Radiation rhombencephalopathy and radiation myelopathy may occur in patients
      months or years after radiotherapy for malignancy of the head and neck. We
      obtained multimodal evoked potentials longitudinally in 26 patients with proven
      nasopharyngeal carcinoma. Recordings were made before radiotherapy and at 1 week,
      3 months, 9 months, 15 months, and 24 months after radiotherapy. All absolute
      latencies of evoked response before and after radiation were within normal
      limits. However, the I-III interpeak latencies of brainstem auditory evoked
      potentials and the onset latencies of motor evoked potentials in the whole group
      of patients at 15 months after radiation were significantly longer than those
      before radiotherapy, whereas the latencies at 24 months were not significantly
      different. The N20 latencies of somatosensory evoked potentials after
      radiotherapy were significantly prolonged at 3 months of follow-up; the
      prolongation then became normal. They indicate that a subclinical reversible
      radiation-induced dysfunction may occur in the auditory, sensory, and motor
      systems.

PMID- 8757031
TI  - Focal paresthesias with cervical magnetic stimulation.
AB  - Subjects undergoing cervical magnetic stimulation with an appropriate coil report
      focal hand paresthesias in a dermatomal distribution, but the physiologic
      accuracy of such subjective experiences has been uncertain. In six subjects, we
      used a butterfly-shaped magnetic coil to stimulate positions on the back of the
      neck at 1-cm intervals, constant output, and random order, while the subject
      estimated location and intensity of paresthesias and sensory nerve action
      potentials (SNAPs) were recorded from the thumb or index finger. Three subjects
      each also had recording of finger accelerometry or compound motor action
      potentials (CMAPs) in the hand and forearm. We found a consistent correlation
      between subjective paresthesias and SNAPs but an appropriate anatomic divergence
      between paresthesias and accelerometry or CMAPs. Focal paresthesias from cervical
      magnetic stimulation are reliable and anatomically accurate, strengthening the
      hypothesis that other magnetic sensory phenomena are valid as well.

PMID- 8757032
TI  - Combined aerobic training and dichloroacetate improve exercise capacity and
      indices of aerobic metabolism in muscle cytochrome oxidase deficiency.
AB  - There is no generally effective therapy for mitochondrial myopathies. In this
      study, we measured responses to combined aerobic training and oral
      dichloroacetate (DCA) therapy in a 25-year-old woman with a mitochondrial
      myopathy caused by cytochrome oxidase deficiency. The patient trained for 14
      weeks, and DCA therapy was begun after 8 weeks. Independent indices of aerobic
      capacity and oxidative metabolism showed substantial improvement. Venous lactate
      concentrations at rest, and after a constant amount of work, decreased by
      approximately 50% after 8 weeks of aerobic training, and by more than 70% with
      the combination of training and DCA treatment. Heart rate at rest and after a
      constant amount of submaximal work decreased progressively. Aerobic capacity on a
      graded submaximal exercise test improved by 71% from baseline by the end of the
      treatment period. 31P magnetic resonance spectroscopy measurements of rate
      constants for recovery of muscle phosphocreatine increased 1.7-fold and
      metabolically active adenine diphosphate increased 2.8-fold after 8 weeks of
      training alone, and 4.5-fold and 23.0-fold after 14 weeks of training plus DCA
      treatment. Responses to the SF-36 Health Survey suggested a marked reduction in
      handicap. Thus, in this open study of a patient with cytochrome oxidase
      deficiency, a combination of aerobic training and DCA treatment resulted in
      substantial improvements in biochemical indices, exercise performance, and
      handicap. We conclude that exercise limitation in patients with mitochondrial
      myopathy may arise from effects of chronic deconditioning in addition to the
      effects of primary mitochondrial dysfunction and may be partially reversed by
      training and administration of DCA.

PMID- 8757033
TI  - Impairment of fast axonal transport in the proximal axons of anterior horn
      neurons in amyotrophic lateral sclerosis.
AB  - We studied the possible impairment of fast axonal transport in patients with
      amyotrophic lateral sclerosis (ALS) to gain some insight into the pathogenesis of
      the disease. We carried out an ultrastructural investigation of the proximal
      axons (axon hillock and initial segment) of the anterior horn neurons on samples
      from 11 ALS patients; specimens from 12 age-matched individuals who died of
      nonneurological diseases served as controls. Eighty-seven proximal axons that
      emanated directly from normal-appearing neurons were examined in each group of
      subjects. Increased smooth endoplasmic reticulum (SER) and the formation of
      bundles of fibrillary SER with a single unit membrane were not uncommonly
      observed in the initial segment of the patients with ALS. In some instances,
      there was loss of the parallel SER arrangement along the longitudinal axis. When
      viewed in transverse sections, the bundles had a tubular appearance. These
      morphologic changes of SER were exclusively demonstrated in patients with ALS. A
      marked increase or accumulation of mitochondria and lysosomes was more common in
      the proximal axons, particularly in the axon hillock, of ALS patients than of
      control subjects. The accumulation of these membrane-bounded cytoplasmic
      organelles suggests that fast axonal transport is impaired in the proximal axons
      of individuals with ALS. In addition, there were Lewy body-like hyaline
      inclusions, lipofuscin granules, and multiple membranous structures in the
      proximal axons. The presence of these unusual structures may also be a reflection
      of axonal transport dysfunction. By contrast, in the central chromatolytic
      neurons, there was not only a decrease in the number of neurofilaments in the
      axon hillock and initial segment, but also of mitochondria, lysosomes, and SER.
      In some instances, none of these cytoplasmic organelles was seen. These findings
      support the notion that the outflow of cytoplasmic constituents from the anterior
      horn cell body into the proximal axon may be impaired in central chromatolytic
      neurons.

PMID- 8757034
TI  - Mutations of the noncoding region of the connexin32 gene in X-linked dominant
      Charcot-Marie-Tooth neuropathy.
AB  - We studied two families with X-linked dominant Charcot-Marie-Tooth neuropathy.
      The clinical findings included onset around age 14 years, with moderate weakness
      of feet extensors and palmar and dorsal interossei, areflexia, distal
      hypesthesia, and slow progressivity. Motor nerve conduction velocities showed
      slowing (20 to 30 m/sec) and EMGs were normal. Genetic linkage analysis revealed
      positive lod scores with the markers of the Xq13.1 region in family 2, but was
      noninformative in family 1. There were no point mutations in the connexin32 gene
      coding region. Instead, family 1 revealed a T-to-G transversion at position -528
      relative to the ATG start codon, whereas family 2 showed a C-to-T transition at
      position -458. The first mutation is located in the nerve-specific connexin32
      promoter just upstream of the transcription start site, the second is located in
      the 5' untranslated region of the mRNA.

PMID- 8757035
TI  - A missense mutation in the neurofibromatosis 2 gene occurs in patients with mild
      and severe phenotypes.
AB  - We identified a missense mutation (T185-->C, Phe62-->Ser) in the
      neurofibromatosis 2 (NF2) gene in a family with mild and severe NF2 phenotypes.
      This mutation was previously reported in an unrelated family in which all
      affected individuals had mild phenotypes. These data demonstrate a lack of
      correlation between NF2 genotype and NF2 phenotype for this mutation.

PMID- 8757036
TI  - Late-onset GM2 gangliosidosis: Ashkenazi Jewish family with an exon 5 mutation
      (Tyr180-->His) in the Hex A alpha-chain gene.
AB  - Late-onset GM2 gangliosidosis is a variant form of Tay-Sachs disease
      characterized by onset of symptoms and signs in adolescence or in early adult
      life. The deficiency of beta-hexosaminidase A (Hex A) in this form of GM2
      gangliosidosis has been invariably associated with the presence of the Gly269-
      >Ser substitution in the alpha-chain. We found two siblings of Ashkenazi Jewish
      descent diagnosed with late-onset GM2 gangliosidosis who were negative for the
      Gly269-->Ser mutation. Analysis of the HEXA gene showed that they were compound
      heterozygotes for the functionally silent 4-bp insertion in exon 11, typical of
      the infantile form of the disease and for a novel mutation, T538-->C, resulting
      in the missense Tyr180-->His. Expression studies in COS-7 cells suggested that
      the effect of this mutation was to decrease the stability of the alpha-chain at
      physiologic temperatures and therefore to indirectly affect the formation of
      mature Hex A.

PMID- 8757037
TI  - Spontaneous multivessel cervical artery dissection in a patient with a
      substitution of alanine for glycine (G13A) in the alpha 1 (I) chain of type I
      collagen.
AB  - Cervical artery dissection occurs spontaneously and in multiple vessels with
      surprising frequency. An underlying arteriopathy is frequently suspected, but
      specific causes of vascular fragility are rarely identified. We describe a 35
      year-old woman who developed multiple cervical artery dissections after scuba
      diving. She had no stigmata of connective tissue disease apart from bluish
      sclerae, and no family history of arterial dissection or congenital
      musculoskeletal disease. Analysis of the COL1A1 gene that encodes the pro alpha
      1(I) chains of type I procollagen revealed a point mutation in one allele,
      resulting in substitution of alanine for glycine (G13A) in about half the alpha
      1(I) chains of type I collagen. Genetic disorders of collagen, such as the mild
      phenotypic variant of osteogenesis imperfecta identified in our patient, should
      be considered in the differential diagnosis of unexplained cervical artery
      dissection.

PMID- 8757038
TI  - A field potential analysis on the effects of lamotrigine, GP 47779, and felbamate
      in neocortical slices.
AB  - We studied the action of the new antiepileptic drugs lamotrigine (LTG), GP 47779
      (the active metabolite of oxcarbazepine), and felbamate (FBM) on stimulus-evoked
      field potentials recorded from rat prefrontal and frontal cortical slices. In the
      presence of physiologic concentrations of extracellular magnesium (1.2 mM) the
      field potential amplitude was not affected by the N-methyl-D-aspartate (NMDA)
      glutamate receptor antagonist, 2-amino-5-phosphonovalerate (APV), while it was
      blocked by the non-NMDA glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline
      2,3-dione (CNQX). When magnesium was removed from the bathing medium, there was a
      significant NMDA-mediated component of the field potential. LTG and GP 47779
      decreased, in a dose-dependent manner, the field potential amplitude under both
      experimental conditions. FBM caused a dose-related decrease of the field
      potential amplitude only in the absence of external magnesium, suggesting a
      selective interaction with an NMDA-mediated component of this potential. These
      findings indicate that the reduction of cortical excitatory transmission might
      represent a common target for new antiepileptic drugs.

PMID- 8757039
TI  - Unprovoked seizures in children with febrile seizures: short-term outcome.
AB  - BACKGROUND: Febrile seizures affect 2 to 4% of children, and 2 to 10% develop
      subsequent unprovoked seizures. Secondary analyses of two large cohorts
      identified neurodevelopmental abnormalities, complex febrile seizures, and a
      family history of epilepsy as predictors of unprovoked seizures. We present an
      analysis of children prospectively followed from their first febrile seizure to
      reassess these three factors, examine factors of equivocal importance, and assess
      the importance of some new factors that we identified as predictors of recurrent
      febrile seizures. METHODS: Children (N = 428) were prospectively identified for a
      first febrile seizure through pediatric emergency departments of four hospitals.
      Information was collected from medical records and interviews with parents.
      Children were followed for 2 years or more. RESULTS: Unprovoked seizures occurred
      in 26 (6%). Neurodevelopmental abnormalities, complex febrile seizures, and a
      family history of epilepsy were associated with an increased risk of unprovoked
      seizures. Recurrent febrile seizures and brief duration of fever before the
      initial febrile seizure were also risk factors. A family history of febrile
      seizures, temperature and age at the initial febrile seizure, sex, and race were
      not associated with unprovoked seizures. CONCLUSIONS: We confirmed the increased
      risk associated with traditionally accepted predictors of epilepsy following
      febrile seizures. Also, the risk clearly increased with recurrent febrile
      seizures. In general, predictors of subsequent unprovoked seizures differ from
      predictors of recurrent febrile seizures. One notable exception, brief duration
      of fever before the initial febrile seizure, predicts both types of outcome and
      may be a marker for an increased susceptibility to seizures.

PMID- 8757040
TI  - Varicella-zoster virus DNA in CSF and arteries in delayed contralateral
      hemiplegia: evidence for viral invasion of cerebral arteries.
AB  - A 78-year-old woman presented with a right basal ganglia infarct 6 weeks after a
      left herpes zoster ophthalmicus. MR angiography showed focal segmental stenosis
      of the proximal segments of the anterior, middle, and posterior cerebral
      arteries. Varicella DNA was detected in the CSF by polymerase chain reaction
      (PCR). Treated with dexamethasone and acyclovir without improvement, she died 1
      month later. There was focal endarteritis in the left anterior, middle, and
      posterior cerebral arteries at autopsy. Varicella DNA was detected by PCR of
      extracts from these vessels but not from the arteries on the right side. This
      study provides further evidence that the vasculopathy after herpes zoster
      ophthalmicus results from direct viral invasion of the vessel wall.

PMID- 8757041
TI  - Incidence of amyotrophic lateral sclerosis in three counties in western
      Washington state.
AB  - We conducted a population-based study of amyotrophic lateral sclerosis (ALS) in
      King, Pierce, and Snohomish counties in western Washington state. Between April
      1, 1990 and March 31, 1995, neurologists diagnosed 235 patients with ALS,
      including 127 men (54%) and 108 women (46%). The incidence rate, age-adjusted to
      the 1990 total U.S. population, was higher for men at 2.1 per 100,000 per year
      (95% CI, 1.3 to 2.9) than for women at 1.9 (95% CI, 1.1, 2.7) and increased with
      age for both men and women. These incidence rates are consistent with other
      studies from northern latitudes.

PMID- 8757042
TI  - Cutis verticis gyrata, underrecognized neurocutaneous syndrome.
AB  - I report two patients with cutis verticis gyrata. Characteristic of this
      neurocutaneous syndrome is the scalp tissue folds that generally run in an
      anterior-posterior direction. Although the etiology of the scalp abnormality is
      unclear, patients may have associated static encephalopathy, seizure disorder, or
      minor ocular abnormalities. The prognosis is benign. Other organ systems are
      spared and there is no malignant transformation of scalp tissue or brain
      parenchyma.

PMID- 8757043
TI  - Conduction aphasia in multiple sclerosis: a case report with MRI findings.
AB  - Aphasia is an uncommon manifestation of MS, which is somewhat surprising because
      various disconnection syndromes, such as conduction aphasia, would be expected to
      occur with some regularity in this white matter disease. We present a case study
      of an MS patient with conduction aphasia associated with a large white matter
      lesion underlying the left supramarginal gyrus.

PMID- 8757044
TI  - Diagnosis of McArdle's disease by molecular genetic analysis of blood.
AB  - We analyzed leukocyte DNA from 32 patients with suspected McArdle's disease, 24
      of whom had biochemically or histochemically proven myophosphorylase deficiency.
      We found that 19 were homozygous for the most common mutation at codon 49, 2 were
      compound heterozygotes, and 1 was a manifesting heterozygote. In six patients, we
      could find only one mutant allele, suggesting a still unidentified mutation on
      the second allele. We were unable to identify any of the known mutations in four
      patients. Our findings indicate that the diagnosis of McArdle's disease can be
      established in approximately 90% of patients using DNA isolated from leukocytes,
      thereby avoiding muscle biopsy.

PMID- 8757045
TI  - Selective atrophy of type 1 muscle fibers in McArdle's disease.
AB  - McArdle's disease is a metabolic myopathy of glycogen utilization caused by an
      absence or deficiency of myophosphorylase. The muscle biopsy features include
      increased deposition of subsarcolemmal glycogen and absent phosphorylase
      histochemical staining of myofibers. We report the clinical and unique pathologic
      findings in three cases of McArdle's disease with prominent type 1 fiber atrophy.

PMID- 8757046
TI  - Idebenone improves cerebral mitochondrial oxidative metabolism in a patient with
      MELAS.
AB  - We report a 36-year-old man with MELAS in whom a 5-month course of high-dose oral
      idebenone, a derivative of coenzyme Q10, increased markedly cerebral metabolic
      ratio of oxygen and oxygen extraction fraction without increased cerebral blood
      flow with PET. The results indicate that idebenone improves mitochondrial
      oxidative metabolism in the brain and suggest a therapeutic potential of
      idebenone for MELAS.

PMID- 8757047
TI  - Dentatorubral-pallidoluysian atrophy proteins in lymphoblastoid cells.
AB  - The genetic defect responsible for dentatorubral-pallidoluysian atrophy (DRPLA)
      is an expansion of a CAG trinucleotide repeat. The DRPLA gene is translated into
      protein in the brain. In this study, we demonstrate that the wild-type and mutant
      genes are also translated into proteins, p190 and p205, in lymphoblastoid cells.
      The correlation between the age of onset and the expansion of polyglutamine
      stretch shown by slower electrophoretic mobility suggests that the polyglutamine
      stretch is directly involved in the acceleration of the disease process.
      Moreover, analysis of the protein in lymphoblastoid cells can be used as a
      diagnostic procedure for DRPLA.

PMID- 8757048
TI  - Selective loss of small myelinated fibers in the lateral corticospinal tract due
      to midbrain infarction.
AB  - Small myelinated fibers in the lateral corticospinal tract (LCST) were
      selectively diminished as compared with large myelinated fibers in a patient with
      an old paramedian midbrain infarct involving the red nuclei, oculomotor nuclei,
      and inferior olivary pseudohypertrophy. Although the physiologic function of
      small myelinated fibers in the LCST is unknown in humans, we hypothesize that
      some of these fibers may include the rubrospinal tract.

PMID- 8757049
TI  - Assessment: neuropsychological testing of adults. Considerations for
      neurologists. Report of the Therapeutics and Technology Assessment Subcommittee
      of the American Academy of Neurology.

PMID- 8757050
TI  - Practice parameter: a guideline for discontinuing antiepileptic drugs in seizure
      free patients--summary statement. Report of the Quality Standards Subcommittee of
      the American Academy of Neurology.

PMID- 8757051
TI  - ApoE epsilon 4 allele and cognitive decline in patients with Alzheimer's disease.

PMID- 8757052
TI  - The phosphodiesterase inhibitor pentoxifylline reduces early side effects of
      interferon-beta 1b treatment in patients with multiple sclerosis.

PMID- 8757053
TI  - Recurrent Bell's palsy.

PMID- 8757054
TI  - Occurrence of adrenocortical insufficiency in adrenomyeloneuropathy.

PMID- 8757055
TI  - Thyroxine exacerbates absence seizures in juvenile myoclonic epilepsy.

PMID- 8757056
TI  - HLA A24 in paraneoplastic cerebellar degeneration with anti-Yo antibody.

PMID- 8757058
TI  - Periodic paralysis.

PMID- 8757057
TI  - Internalization of anti-Hu IgG is not Fc gamma receptor mediated.

PMID- 8757059
TI  - Carotid dissection.

PMID- 8757060
TI  - MRI in Creutzfeldt-Jakob disease.

PMID- 8757061
TI  - Oral sumatriptan.

PMID- 8757062
TI  - Intracranial hypotension.

PMID- 8757063
TI  - Focal suppression-burst.

PMID- 8757064
TI  - Genotypes and phenotypes.

PMID- 8757065
TI  - Neuro-Behcet's disease in Japan.

PMID- 8757067
TI  - Chronic whiplash.

PMID- 8757066
TI  - Docetaxel neuropathy.

PMID- 8757068
TI  - [Vasculitis in rheumatoid arthritis].
AB  - The frequency and histopathological characteristics of systemic vasculitis were
      studied in the autopsy material of 161 patients with rheumatoid arthritis.
      Systemic vasculitis was observed in 36 case (22.4%). In percentage of all cases
      with systemic vasculitis, the most frequently involved organs were the heart
      (66.7%), skeletal muscles (54.8%), and peripheral nerves (52%). The skin was
      involved only in about one third of 36 cases (36%). In most cases the arterioles
      and the small arteries were affected by vasculitis. Three types of vasculitis
      (non specific, fibrinoid necrotic, granulomatous) could be observed
      simultaneously in different vessels or combined in the same vessel. Different
      stages of inflammation could be found simultaneously, reflecting the relapsing
      nature of vasculitis. The frequency, the severity, and the recurrence of
      vasculitis are different aspects of the same phenomenon running usually parallel
      to each other in different organs and on different vessels. Vasculitis lead to
      local ischaemia and regressive changes depend on the number and size of the
      involved vessels. Systemic vasculitis led to death in 19 of 36 cases. Vasculitis
      was detected clinically in 7 of 36 cases. Exitus lethalis depend on the
      localization of the involved vessels. Vasculitis in the heart and brain are more
      life threatening, than that of localized to the skin.

PMID- 8757069
TI  - [Clinical outcome of stereotaxic radiosurgery of the brain].
AB  - Authors render an account of their four years clinical experiences with linac
      based stereotaxic radiosurgery. The first Hungarian stereotaxic radiosurgery team
      have treated 166 patients between 01. 07. 1991 and 01. 11. 1995: 86 suffered from
      brain metastases, 13 of them had primary brain tumors 35, benign brain lesions
      and 32 arteriovenous malformations. The local control rate was found similar to
      presented in the literature (83, 77, 57 and 82%). During 9 months of median
      follow up 44% of brain metastatic cases are alive and only 12% died because of
      cerebral propagation. The primary brain tumors were mostly recurrences (77%)
      after surgery and/or conventional radiotherapy, 31% died in 11 months of median
      follow up. Treating benignomas and arteriovenous malformations there was no need
      for craniotomy at 68 patients. No fatal complications were observed, the rare
      side-effects seemed to be manageable. The method is an effective possibility for
      the non-invasive treatment of the above mentioned brain lesions.

PMID- 8757070
TI  - [Effect of cilazapril in patients with essential hypertension: effect on cardiac
      hypertrophy].
AB  - Numerous antihypertensive drugs exist with different modes of action, which have
      a really effective impact on hypertension. The life expectancy of hypertensive
      patients is known to depend on the degree of damage caused to their target organs
      by the hypertension itself. Cardiovascular hypertrophy and its complications are
      considered to be among the major elements of this process. This work evaluates
      the effectiveness of the long-term treatment of essential hypertensive subjects
      (n = 10) with a long-acting ACE-inhibitor, cilazapril, as concerns their blood
      pressure and cardiac hypertrophy. Cilazapril given orally in a daily dose of 2.5
      mg effectively lowered both the systolic (delta 30 mm Hg) and the diastolic
      (delta 19 mm Hg) blood pressure. No changes were found in body weight or heart
      rate, and only one side-effects (skin rash) was reported. Cilazapril considerably
      decreased the left ventricular mass and hence the hypertrophic index of
      hypertensive patients with cardiac hypertrophy, suggesting that ACE inhibitors
      are effective not only in lowering blood pressure and decreasing hypertrophy, but
      also in lowering the cardiac morbidity and mortality.

PMID- 8757071
TI  - [Purulent meningitis in an adult patient caused by multi-drug resistant
      Streptococcus pneumoniae 19A].
AB  - This is the first report in Hungary about meningitis caused by multiply-resistant
      Streptococcus pneumoniae in a 54 year old woman. The Streptococcus pneumoniae
      serotype 19A was highly resistant to penicillin, ampicillin, chloramphenicol,
      cefuroxime and intermediate resistant to ceftriaxone. The antibiotic treatment
      was started with penicillin and ampicillin. The antibiotic treatment was changed
      to vancomycin + ceftriaxone, vancomycin + rifampicin and vancomycin + imipenem on
      the 2nd, 4th and 11th hospital days, respectively. She died on the 29th day with
      symptoms of sepsis. Necropsy and microscopic examination of the brain revealed
      localised inspissed layer of purulent exsudat over the convexities. Under this
      area the small wessels and capillaries were thrombotic and were surrounded by
      severe degeneration and necrosis in the white matter. RECOMMENDATIONS:
      Streptococcus pneumoniae has to be considered penicillin resistant until the
      organism is proved to be susceptible to penicillin. The authors advise the
      administration of dexamethasone, based on their own favourable 7 years
      experience.

PMID- 8757072
TI  - [Secondary lymphomatous polyposis of the gastrointestinal tract in patients with
      nodal lymphomas].
AB  - Multiplex lymphomatous polyposis is an uncommon disease characterized by polypoid
      accumulations of malignant lymphoid cells within the submucosa of long segments
      of the gastrointestinal tract. Primary gastrointestinal form of disease is
      referred as an extranodal variant of the entity knows as mantle zone lymphoma.
      Rarely, this typical lesion may appear as a secondary involvement of the
      alimentary tract in patients with primary nodal lymphomas. In present article,
      the clinical, histological features of our two cases of primary nodal lymphoma
      presenting with gastrointestinal symptoms and secondary involvement of the bowels
      are discussed. The nodal lymphomas of these patients were classified as a mantle
      zone and a follicle center cell origin lymphoma. The development of
      gastrointestinal symptoms occurred 29 and 41 months after the diagnosis. Our
      cases suggest that lymphomatous polyposis can manifest itself secondarily in
      patients with nodal lymphomas of not only the mantle cell type. The polypoid
      lesion might be mediated by lymphocyte homing receptors and the pattern of
      proliferation can be produced by more than one phenotypically different lymphoma.

PMID- 8757073
TI  - [Postintubation stenosis of the trachea treated by silicone stent implantation].
AB  - 22 patients with postintubation trachea stenosis were treated by silicone stent
      insertion. The stenosis were discovered 107 days after an average 14 days of
      mechanical ventilation. Mechanical and/or laser photocoagulation were followed by
      silicone stent implantation. In 13/22 case this combined therapy resulted a
      significant improvement in the ventilation. After unsuccessful intervention in 2
      cases surgical resection, in 5 cases Montgomery T-tube implantation were
      performed. A tracheotomy was performed in one case, an other patient died due to
      the unresolved main airway stenosis. These results suggest that in the treatment
      of postintubation stenosis the silicone stent implantation is indicated as a
      first line therapy. 12 months after the insertion could attempt to remove the
      prosthesis. In the case of restenosis surgical resection or Montgomery T-tube
      implantation are the choice of therapy.

PMID- 8757074
TI  - [Bone mineral content in osteogenesis imperfecta].
AB  - Bone mineral content (BMC) in the radius of 23 osteogenesis imperfecta (OI)
      patients (1-26 yr) was measured with SPA technique. Comparing the values of OI
      type I. patients with that of type III. patients, the decrease of BMC was more
      prominent in the latter group, however, the two group hadn't been distinct from
      each other at p < 0.05 level. Based on the measurements of 39 relatives (mother,
      father, brother) the method seems not to be helpful in screening of gene-carrying
      relatives because of the high variability of the phenotype of the disease. Follow
      up SPA studies-avoiding the repositioning errors-inform about the therapeutic
      effect.

PMID- 8757075
TI  - [Etiology, investigation and therapy of facial nerve palsy].
AB  - The authors give a description of the causes of the peripheral facial palsy
      (traumas, viral and bacterial infections, tumors and palsies of unknown origin).
      Emphasis is given to those anamnestic data, which are useful in the differential
      diagnostic procedure. Diagnostic methods (modern otologic investigation technics,
      imaging methods, electrodiagnostic tests), which may help in the precise
      diagnosis, are discussed. Authors survey the guidelines in the medical and
      surgical treatment, as well as the electrotherapy of the peripheral facial palsy.
      The prognostic factors of the disease are also discussed. The author's opinion,
      that the effectiveness of the treatment is good, and consequently to treat the
      patients is necessary, and gives high success rate to the doctor.

PMID- 8757076
TI  - [Prenatal ultrasonic diagnosis of cleft lips and palates].
AB  - The purpose of this communication is to demonstrate the possibility of prenatal
      diagnosis of cleft lips and palates by routine ultrasound screening. As
      obstetrical ultrasound improves, anomalies of the fetal face can be diagnosed
      more and more frequently in utero. From 1991 to 1994 9 cases with cleft face
      syndrome were detected prenatally. In 8 cases the presence of cleft lip and
      palate was isolated. In one case the cleft lip and palate was associated with
      phocomelia. In cases with cleft palate the widening of nasal cavity was observed.
      In cases with bilateral cleft palate polyhydramnions were observed twice and
      undulating movements of the tongue were also seen.

PMID- 8757077
TI  - [Adenosine-sensitive atrial tachycardia].
AB  - The authors describe a case of a 71 year old man who suffered from chronic lung
      disease and had atrial tachycardias. 18 mg adenosine terminated his paroxysmal
      supraventricular tachycardia. The Holter monitoring showed that the tachycardia
      began at the late diastole with normal PQ interval, suggesting that an ectopic
      atrial tachycardia was terminated. They propose that adenosine is a "new" drug
      for termination of some form of atrial tachycardia.

PMID- 8757078
TI  - [Centenary of the Millennial Medical Congress].

PMID- 8757079
TI  - [The illness and cause of death of Palatine Joseph and of his first wife].

PMID- 8757080
TI  - [Scientometry, impact factor, citation index: thoughts and considerations].

PMID- 8757081
TI  - [Thyroid and osteoporosis].
AB  - Data indicate that in overt hyperthyroidism the equilibrium of the synthetic and
      degradation processes suffers a change in the bone, there exists an increased
      turnover with a predominance of resorption. Recently many new sensitive markers
      have been developed which are correctly reflecting the altered bone metabolism in
      hyperthyroidism. It is demonstrated that overt hyperthyroidism is a risk factor
      for osteoporosis. Osteopenia improves after the successful treatment of the
      disease, however, a complete restitution may ensue only after years. Lately
      attention has been focused on subclinical hyperthyroidism. Findings indicate that
      osteoporosis can not be demonstrated in premenopausal women with endogenous
      subclinical hyperthyroidism, while this disease may play a role in the
      development of osteopenia in part of post menopausal women. Likewise, in a
      postmenopausal women receiving levothyroxine replacement therapy an increased
      circumspection is required and it is recommended to avoid the administration of a
      levothyroxine dose suppressing TSH secretion. When suppression treatment is
      necessary the administration of the lowest, but the TSH secretion already
      suppressing levothyroxine dose is proposed.

PMID- 8757082
TI  - [The use of teicoplanin for Gram-positive infections in patients with kidney
      transplantation].
AB  - Teicoplanin was used for the treatment of multiresistant Gram-positive
      Staphylococcus aureus, coagulase negative Staphylococcus and Enterococcus
      infections in 15 cases of kidney transplantations. The motive of the application
      was the once per day dosage and the spare of the transplanted kidney. Nosocomial
      infections were the most common. Clinical and microbiological diagnosis was the
      criteria in order to begin the 5-21 days treatment. These patients which were
      infected with Gram positive bacteria, teicoplanin was also effective in
      methicillin-resistant cases. In some mixed infections, after several courses of
      antibiotics, teicoplanin even if combined with other antibiotics could not
      prevent fatal sepsis.

PMID- 8757083
TI  - [New possibility in inguino-femoral hernia repair: laparoscopic herniaplasty].
AB  - The development of minimally invasive surgery brought up the challenge: to repair
      the frequent inguino-femoral hernias laparoscopically. The authors performed 65
      laparoscopic hernioplasties in one year: "transabdominal preperitoneal" technique
      was used in 61 cases und "intraperitoneal onlay mesh" in 4 cases. Fifty-three
      patients were operated on, 12 of them had bilateral hernias. Recurrent hernia was
      the indication in 22 patients (34%). The average operating time was 102 and 144
      minutes in the unilateral and the bilateral cases, respectively. There was no
      wound infection, or general complication. Spontaneously dissolving
      seroma/hematoma of the spermatic cord was noticed and detected by ultrasound in 5
      patients (7.7%). The neuralgia caused by the irritation of the nerves of the
      region in 4 patients (6.1%) disappeared without sequels after treatment with
      vitamins B. The 2 early recurrences (3.2%), considered to be caused by technical
      inexperience, these patients were treated successfully with the "intraperitoneal
      onlay mesh" technique. In the authors' opinion there are definite advantages of
      laparoscopic hernioplasty, namely the minimal postoperative pain, early
      mobilization, shorter hospital stay and early restoration of full physical
      activity (in 1-2 weeks) as well as the known disadvantages of this technique
      (narcosis, longer operative time, intraperitoneal procedure, higher costs).

PMID- 8757084
TI  - [Propolis and poplar bud extract. Some thoughts on alternative medicine].

PMID- 8757086
TI  - [Disseminated histiocytosis X in an adult patient].
AB  - Patient was a 69 year old white female who presented with diffuse brownish
      reddish and normal skin colored nodules of a diameter ranging from 0.5-4 cm.
      Histologic examination showed histiocytosis X. Despite the retinoid-PUVA, and
      combination of glucocorticoid and chemotherapy the disease progressed and in 8
      months after the appearance of the skin lesions the patient expired. The authors
      briefly summarise the clinical, histological features of histiocytosis X and the
      therapeutic possibilities.

PMID- 8757085
TI  - [Local treatment of rheumatic diseases with propolis compounds].
AB  - The authors conducted a single blind, placebo controlled local therapy trial on a
      total of 190 patients involving the use of materials (i) topically and (ii) by
      iontophoresis for pain and/or inflammation of the organs of movement. The
      materials used comprised of the following: (i) purified propolis and propolis
      saturated with antiinflammatory trace metal elements and (ii) propolis saturated
      with trace metal elements and poplar bud ointment saturated with trace metal
      elements also. Both methods of application using all the three preparations
      significantly improved symptoms. The preparations saturated with metallic ions
      were more effective. The mild effect of the placebo treatment is explained by the
      treatment procedure itself. Side effects were not observed.

PMID- 8757087
TI  - [Cochlear implants].
AB  - Cochlear implantation is a method of utmost importance recently employed in ear
      surgery. It makes even speech understanding possible with electrical stimulation
      of the inner ear in case of bilateral total deafness of cochlear origin. The
      authors have performed cochlear implantation for 10 years at the Ear-Nose and
      Throat Clinic of Semmelweis University. Since 1985 different implantation
      techniques have been used in case of 58 patients, both adults and children. The
      authors give account of of technical details, rapidly changing selection criteria
      and the call attention to the problems of peri- and postoperative period and
      rehabilitation, on they basis of their own results. Importance of team-work of
      the ear-surgeon, audiologist, psychologist, physicist and speech-therapist is
      emphasized, because success of the operation is based on proper selection,
      skillful operating techniques and postoperative rehabilitation, as well.

PMID- 8757088
TI  - [Therapy of premenstrual syndrome with medroxyprogesterone acetate in various
      dosages].
AB  - The authors report on their observations with the treatment of premenstrual
      syndrome with gestogens of different dosage. The efficacy of medroxyprogeszteron
      acetate therapy with 20 mg/die and 40 mg/die between the 15. and 26. days of
      menstruation were studied with the help of the premenstrual syndrome index. The
      connection between the efficacy and dosage of the efficacy and period of therapy
      were observed. According to the data the elevated dosage of medroxyprogeszteron
      acetate does not increase the efficacy of therapy. After 3 month treatment period
      67% of the complaints disappeared. Further therapy does not increase efficacy,
      but has been important to prevent remissions. According to the data of this study
      the authors opinion is that a dosage of 20 mg/die medroxyprogeszteron-acetate
      treatment between the 15. and 26. days of menstrual cycle is sufficient to treat
      premenstrual syndrome.

PMID- 8757089
TI  - [Radiotherapy in the treatment of operable breast cancer].
AB  - PURPOSE: to assess the value of radiation therapy in reducing local-regional
      relapses following mastectomy or breast conserving surgery. PATIENTS AND METHODS:
      Between 1983 and 1986, 658 women underwent mastectomy and axillary dissection and
      in 106 cases breast conserving surgery and axillary dissection were done for
      invasive operable breast cancer. Patients with the same pTpN status were assigned
      to subgroups according to whether they received radiation therapy or not.
      RESULTS: 1. After mastectomy: pT1pN(zero) status is not an indication for
      irradiation. 20 mm was defined as a cut off diameter in locoregional recurrence:
      pT 1/c versus pT2 p = 0.0590. In particular, patients with pT2 tumors, located in
      the medial-central subregions, had better locoregional results after irradiation
      (p = 0.0328). The condition of axillary lymph nodes was a significant predictor
      of locoregional recurrence (p = 0.0000) but between pN(zero) and pN 1/a there was
      no essential difference (p = 0.9594). 2. After breast conserving surgery:
      Patients receiving radiation therapy had better results than unirradiated ones (p
      = 0.0002). The rate of loco-regional relapses was 13.8% and 52.4% respectively.
      Radiation therapy was able to decrease a tumor bed relapses and even then the
      diameter of tumor vas < or = 10 mm (p = 0.0218). Local recurrence was more likely
      in the presence of extensive intraductal components, as opposed to no extensive
      components (p = 0.002). Overall survival after mastectomy or breast conserving
      surgery, when patients with the same pTpN status vere compared, was similar (p =
      0.6293). CONCLUSION: after mastectomy pT1N(zero) status is not an indication for
      irradiation. The critical tumor diameter was 20 mm in the locoregional tumor
      control. Breast irradiation after conservative surgery resulted in a decrease in
      local recurrence and even then minimal breast cancer.

PMID- 8757090
TI  - [H2-receptor antagonists and alcohol: clinical significance].
AB  - The aim of the review is to evaluate the putative clinical interactions between
      alcohol metabolism and the administration of H2-receptor antagonists. Places of
      the first-pass metabolism of ethanol in the body have been investigated as well.
      According to the in vitro experimental results the H2-receptor antagonists can
      inhibit the ethanol metabolism which may have clinical relevance. When low doses
      of alcohol (below 0.3 g/kg) are given per os, the administration of H2-receptor
      antagonists results in an increase in the blood ethanol concentrations. Since
      that challenged increase never exceeds the level of 0.3/1000 blood alcohol
      concentration, it has hardly any clinical or medico-legal significance.

PMID- 8757091
TI  - [Albrecht von Haller (1708-1777)].

PMID- 8757092
TI  - [The use of Hungarian medical terminology].

PMID- 8757093
TI  - [Neural pathways--neural networks].
AB  - During the past two decades, the introduction of several modern neuroanatomical
      approaches resulted in a rapidly growing body of informations about neuronal
      pathways in the central nervous system. Several new neuronal connections between
      brain areas have been discovered, and the chemical nature (neurotransmitter
      content) of pathways has been determined by using highly specific neurochemical
      and immunohistochemical techniques. On the basis of these new informations, our
      knowledge and attitude to the general organization of neuronal connections have
      been changed substantially: 1. Neuronal pathways are multi-neuronal networks
      rather than simple chain of neurons, wherein informations are forwarded between
      two brain areas bidirectionally, meanwhile several additional brain regions are
      inter-connected by axon-collaterals. 2. A single neuronal cell may synthesize
      several neuropeptides which co-localized in and released from nerve terminals,
      and depending on the target sites they may act as neurotransmitters or
      neurohormones. In certain conditions, neuropeptides may also function as nerve
      growth factors by supporting the survival or the restitution of neuronal cells.
      3. By the introduction of molecular imaging in neuroscience (visualization of
      oncogenes, specific mRNA's, etc), topographical studies on neuronal pathways are
      more and more completed by functional informations.

PMID- 8757094
TI  - [Accidents of the elderly].
AB  - The topic of accidents in elderly population has been studied on 2055 injured
      older than 65 years. The severity of injuries indicates the importance of
      accidents in this age-group. The proportion of fractures in the elderly
      population is twice of the average-in females over 75 years of age they take the
      half of the total number of injuries. While the incidence rate of males in the
      whole material with all of the age groups is twice of that of females, in elderly
      population it turns into equal. The rate of home-accidents grows with ageing. The
      elderly people specially the males suffer a high number of road traffic accidents
      as pedestrians or riding their bicycles. The severity of injuries and the broken
      health status in elderly people is a major problem both for the health care and
      the whole society.

PMID- 8757095
TI  - [Quality of the performance of clinical laboratories].
AB  - The quality performance of clinical laboratories plays a basic role in the
      quality and effectiveness of health care. The reliability of laboratory tests,
      however, depends on the quality assurance system existing in the working place,
      which comprises not only the analytical activities but includes all preventive
      measures and their regular control in connection with the preanalytical phase, as
      well as the plausibility control and interpretation of results. The external
      quality assessment of laboratory work gives information about the systematic
      errors existing between results of different laboratories, and it helps to
      discover rough errors of either random or systematic origin. The external quality
      assessment of medical laboratories has its beginning in early 1970's in Hungary
      and since 1975 it is organized continuously by the National Institute. In recent
      years, the external quality assessment of laboratories is performed in
      cooperation and support of the INSTAND e.V./WHO Collaborating Center
      (Dusseldorf). The paper surveys the quality performance of laboratories in
      routine clinical chemistry, haematology, blood-coagulation, hormone and blood-gas
      analysis. Moreover, the evaluation of results on the basis of reference and
      assigned values measured in the reference laboratories and according to the
      statistical error of results of participants is also discussed. Further
      improvement in the quality performance of health laboratory service needs the
      introduction of unified quality system which includes details of all elements of
      knowledges and technical activities necessary to fulfill requirement of reliable
      and effective laboratory work.

PMID- 8757096
TI  - [Diagnostic value of C-reactive protein levels in children with bone marrow
      transplantation].
AB  - Serum quantitative C-reactive protein concentrations were measured in 16 bone
      marrow transplanted children at 202 occasions during and after the transplant
      period. Serum C-reactive protein concentrations were moderately increased in
      patients with viral and protozoon infections (5-67 mg/l). High values were
      measured in patients with bacterial and fungal infections. The C-reactive protein
      level was between 15-102 mg/l in Coag. neg. Staphylococcus sepsis, and 160-178
      mg/l in Pseudomonas aeruginosa infection, when blood cultures were positive.
      Values of 154-358 mg/l was found with Candida sepsis. C-reactive protein levels
      were 10-17 mg/l in 7 acute GvHD episodes, only one of the patients had high level
      (325 mg/l) in GvHD. In these cases the condition was very severe and affected the
      total surface of the skin and the gastrointestinal tract also. C-reactive protein
      becomes a valuable aid as laboratory parameter in the diagnosis of bone marrow
      transplant recipients with suspected bacterial infection and in monitoring of
      therapeutic efficiency.

PMID- 8757097
TI  - [Massive haemothorax caused by intralobar pulmonary sequestration].
AB  - The authors present the case of a young male with massive haemothorax caused by
      intralobar bronchopulmonary sequestration. Angiography is necessary for the exact
      diagnosis of bronchopulmonary sequestration. The most common site of
      intrapulmonary type sequestration is the left lower lobe of the lung. In this
      case the aberrant artery was originated from the abdominal aorta. During
      thoracotomy after ligature of the aberrant vessels S5,S10 segmentectomy was
      performed. The authors emphasize that the rare cause of rapid anaemia in
      consequence of haemothorax could be intralobar bronchopulmonary sequestration.

PMID- 8757099
TI  - [Long-term results of surgical treatment of cardiac myxomas].
AB  - We have reviewed our clinical experience in the diagnosis and management of 50
      cases of cardiac myxoma seen over a 20 year period, 1974 to 1994. There were 17
      males and 33 females, their ages ranged from 16 to 81 years (mean 55.2 years).
      Echocardiography confirmed the diagnosis in all patients. The location of myxomas
      was as follows: left atrial alone in 42 patients, right atrial alone in 3, right
      ventricular alone in 1, left + right atrial in 2, left + right atrial + right
      ventricular in 1, and left atrial eft ventricular in 1. Nineteen patients were
      operated on within 48 hours following the diagnosis. All tumors were successfully
      removed with the aid of cardiopulmonary bypass. The hospital mortality rate was
      10%. Excision of the tumor resulted in marked symptomatic improvement. There was
      one late death. The current survivors are asymptomatic at a mean follow-up of
      76,4 months (range 1-241 months). Echocardiographic studies were performed in all
      survivors and no recurrences have been observed. We conclude that excision of
      cardiac myxomas is curative and long-term survival is excellent. Radical tumor
      excision may prevent recurrence.

PMID- 8757098
TI  - [Effect of interferon-alpha2b therapy in chronic hepatitis C].
AB  - In chronic hepatitis C the interferon treatment given three times a week in a
      dosage of 3 million units (MU) normalizes the values of alanin-amino-transferase
      in a part of cases (25-40%), and produces bettering in the subjective complains
      of patients. In the short term therapy (3-6 months) the activity of ALT increases
      again after leaving the therapy, and the disease becomes active. The aim of this
      multicenter study in Hungary was to give newer data in the case of longterm
      efficacy with alpha-interferon. Ninety-one patients with chronic hepatitis C were
      selected into the open prospective clinical study in university and hospital
      departments. Treatment protocol was the following: Patients with chronic
      hepatitis C diagnosed by clinical and histological methods were treated with
      interferon-alpha 2B given 3 times a week in a dosage of 3 MU. Treatment period
      had lasted for one year and afterwards the patient had been on control for an
      other half a year. In non responder cases after 3 month treatment with interferon
      the dose of therapy was increased for 3 x 5 MU. In 37 cases (40.6%) out of 91
      patients the authors found longterm sustained remission and in other 22 cases
      (24.2%) they observed a partial remission (among them 5 cases with late relapse).
      The rate of longterm sustained remission under 40 years was higher, than above
      40. Higher rate was found when the treatment was started with a shorter
      chronicity of the disease. On te basis of the results the authors conclude:
      Interferon-alpha 2B is a good therapeutic modality for the treatment of patients
      with chronic hepatitis C. Efficacy of therapy is higher in younger patients and
      also in earlier application.

PMID- 8757100
TI  - [The Hippel-Lindau syndrome is often misdiagnosed and its frequency
      underestimated].
AB  - Results of epidemiological investigations were published only recently. The
      syndrome is particularly seldom diagnosed if the examination program is carried
      out not carefully enough in the case of patients, who have to be taken into
      consideration on the basis of different lesions. The syndrome differs from the
      majority of the hereditary diseases in the possibility of an efficient therapy
      improving the prognosis decisively.

PMID- 8757101
TI  - [HIV infection es IgA nephropathy].
AB  - Similar immunological abnormalities exist in IgA nephropathy and HIV infection
      and several IgA nephropathy cases were reported in HIV-infected patients. To
      estimate the number of HIV-infected patients in IgA nephropathy, 80 patients with
      IgA nephropathy were studied for HIV-1 and HIV-2 antibody seropositivity.
      Although they failed to detect HIV positivity among their IgA nephropathy
      patients, because of the increasing number of people are being infected with HIV,
      the screening of IgA nephropathy patients for HIV infection would warrant.

PMID- 8757102
TI  - [Glossopharyngeal neuralgia with syncope].
AB  - Glossopharyngeal neuralgia an uncommon craniofacial pain syndrome. An association
      with syncope is even less common. The authors give a short case report of 74-year
      old woman, who has glossopharyngeal neuralgia associated with syncope. During
      attacks 10 secundum asystolia was recorded in the ECG. The electrophysiologic
      study of heart was normal, the carotid test resulted 3 secundum asystolia without
      clinical symptoms. The electroencephalogram and computertomogram of brain were
      normal. Carbamazepine and demand pacemaker were effective in controlling the
      symptoms of the patient. Finally, aetiology, pathogenesis and treatment of
      glossopharyngeal neuralgia are discussed.

PMID- 8757103
TI  - [The beginnings of medical journal publishing in Hungary].

PMID- 8757104
TI  - [Everyday life at the (New) St. John Hospital in historic and current
      newsletters].

PMID- 8757105
TI  - [Recent changes in breast cancer surgery].
AB  - After former radical extensions the breast cancer surgery now tends to accept the
      necessary minimum principle. There are surveys which rated the local recurrence
      to the width of the intact margin around the tumour; they are aware of the
      decisive role of extensive intraductal component to have an influence on the
      local recurrence. Leaving out irradiation in selected groups is a part of the
      less aggressive tendency of breast cancer treatment. The omitment of the routine
      use of axillary dissection is under further consideration as well. The
      intraoperative mapping of lymph nodes looks promising in assessing their tumorous
      involvement. The prognostic role of dissection can be replaced by the
      immunoreactive hepatocyte growth factor. Timing of the operation adjusted to the
      menstrual phase seems to improve the survival in case of those patients who were
      operated on in the luteal phase.

PMID- 8757106
TI  - [Postpartum hysterectomy].
AB  - Between the 1st July 1990 and the 30th June 1995, 34 caesarean hysterectomies and
      2708 (22%) caesarean sections were performed from 12,227 births on the I.
      Department of Obstetrics and Gynaecology Semmelweis University Medical School in
      Budapest. From all 34 cases, hysterectomy were performed in 9 cases (26%) after
      complicated delivery, in other 9 cases (26%) during elective caesarean section
      and in 16 cases (47%) during urgent caesarean section. The incidence of caesarean
      hysterectomy is 2.7/1000 labour in our study. We listed the placenta increta,
      placenta accreta, placenta adherens, placenta praevia, uteroplacental apoplexia,
      scar disruption, uterus rupture, atony, sepsis puerperalis, abruptio placentae,
      haematoma paravaginale as urgent indications and so elective indications were
      myoma uteri, cervical carcinoma, ovarial tumour and in-situ cervical carcinoma.
      We collect the elective and urgent indications of caesarean hysterectomy and
      summarize the possible operative and postoperative complications in our study.

PMID- 8757108
TI  - [Immunophenotyping of childhood leukemias--results of the first 100 bone marrow
      tests].
AB  - The authors used a cell-surface-marker analysis by flow cytometry for
      immunophenotyping of pediatric leukemia from 1993. Results of their first one
      hundred cases were summarized. They examined 68 bone-marrow samples from 58
      patients affected by leukemia, and diagnosed 19 acute myeloid leukemia (32%), 5 T
      cell acute lymphoid leukemia (8%), 32 B-cell acute lymphoid leukemia (54%) and 2
      biphenotypic leukemia (5%). A higher CD34 antigen positivity was found compared
      to adults. They analysed the incidence and prognostic significance of myeloid +
      lymphoid leukemia and lymphoid + myeloid leukemia cases. Nondiagnostic and
      unsuccessful cases were got according to the literature.

PMID- 8757107
TI  - [Immunohistochemical study of hepatitis B and D virus antigens (HBsAg, HBcAg,
      HDAg) in chronic liver diseases].
AB  - Authors have investigated the hepatitis B and D virus antigens in the liver
      tissue of 30 HBsAg and/or anti-HD seropositive patients (23 males, 7 females,
      age: 20-65, mean: 44 years) by immunohistochemical method. The
      immunohistochemical identification of HBsAg, HBcAg and HDAg in 42 liver sample
      (36 obtained by percutaneous biopsy, 6 from dissection) of 30 patients was
      performed with Dako and Sorin Biomedica kits. The detailed virus serologic
      examinations were carried out with Biomedica and Abbott kits by radioimmunoassay
      and ELISA methods. Examining 36 liver tissue samples of 27 HBsAg seropositive
      patients, HBsAg could be demonstrated in 31 cases. Each patient suffering of
      active HBV and/or HDV replication was HBsAg positive by immunohistochemistry,
      while the tissue samples of patients in integrational phase of HBV infection were
      positive in only 9 cases of 14. There was no HBsAg tissue positivity in HBsAg
      seronegative cases. 7 of 16 tissue samples of 12 patients classified to active
      HBV replication state were HBcAg positive by immunohistochemistry. HBcAg could be
      detected in the liver tissue of each HBe seropositive patient, while in only 3 of
      8 cases with only IgM anti-HBc seropositivity (indicating low level of HBV
      replication). Tissue HBcAg positivity, indicating active virus replication, was
      verified in 2 of 11 patients classified to HBV integration state by serology.
      Authors detected HDAg tissue positivity only in cases with serologically active
      HDV replication (IgM anti-HD seropositive) and HDAg could also be identified from
      liver tissue in each IgM anti-HD seropositive case. No HBsAg, HBcAg and HDAg
      tissue positivity was observed in HBsAg negative cases. Authors emphasise mainly
      the importance of immunohistochemical detection of HBcAg and HDAg completing the
      serologic diagnosis of chronic HBV and HDV infections, helping the verification
      or exclusion of active virus replication being essential for selecting adequate
      therapy.

PMID- 8757110
TI  - [Cost-benefit analysis of the therapy of lipid metabolism disorders].

PMID- 8757109
TI  - [Neonatal primary hyperparathyroidism].
AB  - The authors report on a case of severe primary hyperparathyroidism with clinical
      signs from birth. The boy was admitted because of poor somatomental development,
      hypotony, hepatosplenomegaly and osseous abnormalities, resembling those of
      rachitis. Laboratory data showed the typical findings of primary
      hyperparathyroidism. The authors performed parathyroidectomy with simultaneous
      heterotopic parathyroid tissue autotransplantation. Histology revealed
      parathyroid chief cell hyperplasia. Because of the hypercalcaemia and clinical
      signs persisting after the operation they removed the parathyroid autografts.
      Since this later was ineffective they performed a left sided neck dissection on
      the side of the excessive parathormone production. The child became hypocalcaemic
      necessitating calcium and vitamin D administration. He is now 17 months after the
      last operation. His somatomental development is accelerated. In connection with
      the case the authors surveyed the literature of this rare entity.

PMID- 8757112
TI  - Meteorite claims revitalize plans for further Mars missions.

PMID- 8757111
TI  - 'MARS mania' and the right to celebrate.

PMID- 8757113
TI  - India loses vaccine manufacturing project.

PMID- 8757114
TI  - Forum to advance trials for AIDS therapies.

PMID- 8757115
TI  - German groups debate ethics rules.

PMID- 8757116
TI  - Japan shuns radishes after 'possible link' to E. coli.

PMID- 8757117
TI  - Drugs institute gives grant for cocaine vaccine.

PMID- 8757118
TI  - Smoke signals.

PMID- 8757119
TI  - BSE and risk to humans.

PMID- 8757120
TI  - Opening a martian can of worms?

PMID- 8757121
TI  - Life beyond mars.

PMID- 8757122
TI  - RNA processing. Death by decapitation for mRNA.

PMID- 8757123
TI  - Supramolecular chemistry. Nanotechnology and nucleotides.

PMID- 8757124
TI  - Fat metabolism. Slimming with leaner enzyme.

PMID- 8757125
TI  - Bracken ptaquiloside in milk.

PMID- 8757126
TI  - Human leptin characterization.

PMID- 8757127
TI  - tRNA-dependent asparagine formation.

PMID- 8757128
TI  - Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of
      Spemann's organizer.
AB  - An abundant cDNA enriched in Spemann's organizer, cerberus, was isolated by
      differential screening. It encodes a secreted protein that is expressed in the
      anterior endomesoderm. Microinjection of cerberus mRNA into Xenopus embryos
      induces ectopic heads, and duplicated hearts and livers. The results suggest a
      role for a molecule expressed in the anterior endoderm in the induction of head
      structures in the vertebrate embryo.

PMID- 8757129
TI  - A DNA-based method for rationally assembling nanoparticles into macroscopic
      materials.
AB  - Colloidal particles of metals and semiconductors have potentially useful optical,
      optoelectronic and material properties that derive from their small (nanoscopic)
      size. These properties might lead to applications including chemical sensors,
      spectroscopic enhancers, quantum dot and nanostructure fabrication, and
      microimaging methods. A great deal of control can now be exercised over the
      chemical composition, size and polydispersity of colloidal particles, and many
      methods have been developed for assembling them into useful aggregates and
      materials. Here we describe a method for assembling colloidal gold nanoparticles
      rationally and reversibly into macroscopic aggregates. The method involves
      attaching to the surfaces of two batches of 13-nm gold particles non
      complementary DNA oligonucleotides capped with thiol groups, which bind to gold.
      When we add to the solution an oligonucleotide duplex with 'sticky ends' that are
      complementary to the two grafted sequences, the nanoparticles self-assemble into
      aggregates. This assembly process can be reversed by thermal denaturation. This
      strategy should now make it possible to tailor the optical, electronic and
      structural properties of the colloidal aggregates by using the specificity of DNA
      interactions to direct the interactions between particles of different size and
      composition.

PMID- 8757130
TI  - Organization of 'nanocrystal molecules' using DNA.
AB  - Patterning matter on the nanometre scale is an important objective of current
      materials chemistry and physics. It is driven by both the need to further
      miniaturize electronic components and the fact that at the nanometre scale,
      materials properties are strongly size-dependent and thus can be tuned
      sensitively. In nanoscale crystals, quantum size effects and the large number of
      surface atoms influence the, chemical, electronic, magnetic and optical
      behaviour. 'Top-down' (for example, lithographic) methods for nanoscale
      manipulation reach only to the upper end of the nanometre regime; but whereas
      'bottom-up' wet chemical techniques allow for the preparation of mono-disperse,
      defect-free crystallites just 1-10 nm in size, ways to control the structure of
      nanocrystal assemblies are scarce. Here we describe a strategy for the synthesis
      of 'nanocrystal molecules', in which discrete numbers of gold nanocrystals are
      organized into spatially defined structures based on Watson-Crick base-pairing
      interactions. We attach single-stranded DNA oligonucleotides of defined length
      and sequence to individual nanocrystals, and these assemble into dimers and
      trimers on addition of a complementary single-stranded DNA template. We
      anticipate that this approach should allow the construction of more complex two-
      and three-dimensional assemblies.

PMID- 8757131
TI  - Genetically lean mice result from targeted disruption of the RII beta subunit of
      protein kinase A.
AB  - Cyclic AMP is an important second messenger in the coordinated regulation of
      cellular metabolism. Its effects are mediated by cAMP-dependent protein kinase
      (PKA), which is assembled from two regulatory (R) and two catalytic (C) subunits.
      In mice there are four R genes (encoding RI alpha, RI beta, RII alpha, and RII
      beta) and two C gene (encoding C alpha and C beta), expressed in tissue-specific
      patterns. The RII beta isoform is abundant in brown and white adipose tissue and
      brain, with limited expression elsewhere. To elucidate its functions, we
      generated RII beta knockout mice. Here we report that mutants appear healthy but
      have markedly diminished white adipose tissue despite normal food intake. They
      are protected against developing diet-induced obesity and fatty livers. Mutant
      brown adipose tissue exhibits a compensatory increase in RI alpha, which almost
      entirely replaces lost RII beta, generating an isoform switch. The holoenzyme
      from mutant adipose tissue binds cAMP more avidly and is more easily activated
      than wild-type enzyme. This causes induction of uncoupling protein and elevations
      of metabolic rate and body temperature, contributing to the lean phenotype. Our
      results demonstrate a role for the RII beta holoenzyme in regulating energy
      balance and adiposity.

PMID- 8757132
TI  - Where in the brain does visual attention select the forest and the trees?
AB  - The perceptual world is organized hierarchically: the forest consists of trees,
      which in turn have leaves. Visual attention can emphasize the overall picture
      (global form) or the focal details of a scene (local components).
      Neuropsychological studies have indicated that the left hemisphere is biased
      towards local and the right towards global processing. The underlying attentional
      and perceptual mechanisms are maximally impaired by unilateral lesions to the
      temporal and parietal cortex. We measured brain activity of normal subjects
      during two experiments using 'hierarchically' organized figures. In a directed
      attention task, early visual processing (prestriate) areas were activated:
      attention to the global aspect of the figures activated the right lingual gyrus
      whereas locally directed attention activated the left inferior occipital cortex.
      In a subsequent divided attention task, the number of target switches from local
      to global (and vice versa) covaried with temporal-parietal activation. The
      findings provide direct evidence for hemispheric specialization in global and
      local perception; furthermore, they indicate that temporal-parietal areas exert
      attentional control over the neural transformations occurring in prestriate
      cortex.

PMID- 8757133
TI  - Reward expectancy in primate prefrontal neurons.
AB  - The prefrontal cortex is important in the organization of goal-directed
      behaviour. When animals are trained to work for a particular goal or reward,
      reward 'expectancy' is processed by prefrontal neurons. Recent studies of the
      prefrontal cortex have concentrated on the role of working memory in the control
      of behaviour. In spatial delayed-response tasks, neurons in the prefrontal cortex
      show activity changes during the delay period between presentation of the cue and
      the reward, with some of the neurons being spatially specific (that is, responses
      vary with the cue position). Here I report that the delay activity in prefrontal
      neurons is dependent also on the particular reward received for the behavioural
      response, and to the way the reward is given. It seems that the prefrontal cortex
      may monitor the outcome of goal-directed behaviour.

PMID- 8757134
TI  - Visual projection map specified by topographic expression of transcription
      factors in the retina.
AB  - Topographical maps of neuronal connectivity occur in various brain regions. In
      the visual system of birds, retinal ganglion-cell axons from the anterior retina
      connect to a posterior part of the optic tectum, and posterior retinal axons
      connect to the anterior part, thereby establishing a point-to-point projection
      map. The chemoaffinity theory predicts that the orderly retinotectal projection
      is generated by a topographical arrangement of molecules. We report here that we
      have found several genes topographically expressed along the nasotemporal
      (anterior-posterior) axis in the embryonic chicken retina. Among these, two
      transcriptional regulators, belonging to the winged-helix family are expressed in
      a mutually exclusive manner in either the nasal or temporal part of the retina.
      Misexpression of each factor causes misprojection on the tectum along the
      rostrocaudal axis, showing that topographical expression of these transcription
      factors controls formation of the retinotectal map.

PMID- 8757135
TI  - Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the
      CXC chemokine PBSF/SDF-1.
AB  - The chemokines are a large family of small, structurally related cytokines. The
      physiological importance of most members of this family has yet to be elucidated,
      although some are inducible inflammatory mediators that determine leukocyte
      chemotaxis. Pre-B-cell growth-stimulating factor/stromal cell-derived factor-1
      (PBSF/SDF-1) is a member of the CXC group of chemokines PBSF/SDF-1 stimulates
      proliferation of B-cell progenitors in vitro and is constitutively expressed in
      bone-marrow-derived stromal cells. Here we investigate the physiological roles of
      PBSF/SDF-1 by generating mutant mice with a targeted disruption of the gene
      encoding PBSF/SDF-1. We found that mice lacking PBSF/SDF-1 died perinatally and
      that although the numbers of B-cell progenitors in mutant embryos were severely
      reduced in fetal liver and bone marrow, myeloid progenitors were reduced only in
      the bone marrow but not in the fetal liver, indicating that PBSF/SDF-1 is
      responsible for B-cell lymphopoiesis and bone-marrow myelopoiesis. In addition,
      the mutants had a cardiac ventricular septal defect. Hence, we have shown that
      the chemokine PBSF/SDF-1 has several essential functions in development.

PMID- 8757136
TI  - Functional interaction of beta-catenin with the transcription factor LEF-1.
AB  - The cytoplasmic proteins beta-catenin of vertebrates and armadillo of Drosophila
      have two functions: they link the cadherin cell-adhesion molecules to the
      cytoskeleton, and they participate in the wnt/wingless signal pathway. Here we
      show, in a yeast two-hybrid screen, that the architectural transcription factor
      LEF-1 (for lymphoid enhancer-binding factor) interacts with beta-catenin. In
      mammalian cells, coexpressed LEF-1 and beta-catenin form a complex that is
      localized to the nucleus and can be detected by immunoprecipitation. Moreover,
      LEF-1 and beta-catenin form a ternary complex with DNA that splays an altered DNA
      bend. Microinjection of LEF-1 into XenoPus embryos induces axis duplication,
      which is augmented by interaction with beta-catenin. Thus beta-catenin regulates
      gene expression by direct interaction with transcription factors such as LEF-1,
      providing a molecular mechanism for the transmission of signals, from cell
      adhesion components or wnt protein to the nucleus.

PMID- 8757137
TI  - An essential component of the decapping enzyme required for normal rates of mRNA
      turnover.
AB  - A major pathway of messenger RNA degradation in eukaryotic cells is initiated by
      shortening of the poly(A) tail, which, at least in yeast, triggers a decapping
      reaction, thereby exposing the mRNA to 5' --> 3' degradation. Decapping is the
      key step in this decay pathway because the transcript body is rapidly degraded
      following decapping. Accordingly, decapping is the site of numerous controls,
      including inhibition of decapping by the poly(A) tail and modulation of mRNA
      decapping rate by specific sequences. Moreover, a specialized decay pathway that
      degrades aberrant transcripts triggers rapid mRNA decapping independently of
      poly(A)-tail shortening. We have identified a yeast gene, termed DCP1, that
      encodes the decapping enzyme, or an essential component of a decapping complex.
      The protein Dcp1 is required for the normal decay of many unstable and stable
      yeast mRNAs, as well as mRNAs that are decapped independently of deadenylation.
      These results indicate that mRNA-specific rates of decapping, and thus decay,
      will result from differences in the interaction of the DCP1 decapping enzyme with
      individual transcripts.

PMID- 8757138
TI  - Structure of the WW domain of a kinase-associated protein complexed with a
      proline-rich peptide.
AB  - The WW domain is a new protein module with two highly conserved tryptophans that
      binds proline-rich peptide motifs in vitro. It is present in a number of
      signalling and regulatory proteins, often in several copies. Here we investigate
      the solution structure of the WW domain of human YAP65 (for Yes kinase-associated
      protein) in complex with proline-rich peptides containing the core motif PPxY.
      The structure of the domain with the bound peptide GTPPPPYTVG is a slightly
      curved, three-stranded, antiparallel beta-sheet. Two prolines pack against the
      first tryptophan, forming a hydrophobic buckle on the convex side of the sheet.
      The concave side has three exposed hydrophobic residues (tyrosine, tryptophan and
      leucine) which form the binding site for the ligand. A non-conserved isoleucine
      in the amino-terminal flanking region covers a hydrophobic patch and stabilizes
      the WW domain of human YAP65 in vitro. The structure of the WW domain differs
      from that of the SH3 domain and reveals a new design for a protein module that
      uses stacked aromatic surface residues to arrange a binding site for proline-rich
      peptides.

PMID- 8757139
TI  - Crystal structure of a PDZ domain.
AB  - PDZ domains (also known as DHR domains or GLGF repeats) are approximately 90
      residue repeats found in a number of proteins implicated in ion-channel and
      receptor clustering, and the linking of receptors to effector enzymes. PDZ
      domains are protein-recognition modules; some recognize proteins containing the
      consensus carboxy-terminal tripeptide motif S/TXV with high specificity. Other
      PDZ domains form homotypic dimers: the PDZ domain of the neuronal enzyme nitric
      oxide synthase binds to the PDZ domain of PSD-95, an interaction that has been
      implicated in its synaptic association. Here we report the crystal structure of
      the third PDZ domain of the human homologue of the Drosophila discs-large tumour
      suppressor gene product, DlgA. It consists of a five-stranded antiparallel beta
      barrel flanked by three alpha-helices. A groove runs over the surface of the
      domain, ending in a conserved hydrophobic pocket and a buried arginine; we
      suggest that this is the binding site for the C-terminal peptide.

PMID- 8757140
TI  - Molecular mechanism of drug photosensitization: VIII. Effect of inorganic ions on
      membrane damage photosensitized by naproxen.
AB  - The inhibitory effect of Cu2+, Mn2+, Co2+, and I- on naproxen-induced
      photohemolysis was investigated. In order to better understand this effect, these
      ions were also tested for lipid peroxidation and protein crosslinking, which are
      among the main processes involved in erythrocyte membrane damage. The overall
      results support the hypothesis that metal cations act via a redox scavenging of
      the radicals which are produced on the lipid component of the membrane. This
      process occurs through hydrogen abstraction operated by photogenerated naproxen
      radicals. Moreover, copper can also act as a superoxide anion scavenger: its
      decay is noxious in photohemolysis, whereas it is not in lipid peroxidation.
      Metal cations, besides, are not able to scavenge protein crosslinking. On the
      other hand, iodide is able to reduce both processes because it acts as a heavy
      atom, favoring intersystem crossing to the unreactive triplet state of the drug,
      thus reducing naproxen photolysis and, as a consequence, the amount of the
      damaging species produced. This mechanism was supported by luminescence
      experiments performed in the absence and in the presence of iodide.

PMID- 8757141
TI  - Metal-ion-dependent oxidative DNA cleavage by transition metal complexes of a new
      water-soluble salen derivative.
AB  - A new water-soluble, salen [salen = bis(salicylidene) ethylenediamine]-based
      ligand, 3 was developed. Two of the metal complexes of this ligand, i.e., 3a,
      [Mn(III)] and 3b, [Ni(II)], in the presence of cooxidant magnesium
      monoperoxyphthalate (MMPP) cleaved plasmid DNA pTZ19R efficiently and rapidly at
      a concentration approximately 1 microM. In contrast, under comparable conditions,
      other metal complexes 3c, [Cu(II)] or 3d, [Cr(III)] could not induce any
      significant DNA nicking. The findings with Ni(II) complex suggest that the DNA
      cleavage processes can be modulated by the disposition of charges around the
      ligand.

PMID- 8757142
TI  - An electron spin resonance study and antimicrobial activity of copper(II)
      phenanthroline complexes.
AB  - The antimicrobial activities of some copper(II) binary complexes with
      unsubstituted and different substituted phenanthroline ligands were investigated.
      A considerable increase in the biocidal activity of the ligands on being
      coordinated with the copper(II) ions was observed in terms of their minimum
      inhibitory concentration (MIC) values. EPR measurements were performed at room
      and low temperature with the aim of gaining an insight into the
      structure/activity relationship of these complexes. Subtle differences in the
      chemical arrangement result in appreciable differences in the antimicrobial
      activity. Copper(II) complexes with 2,9-dimethyl derivative phenanthrolines were
      observed to be more active against Staphylococcus aureus and Escherichia coli.

PMID- 8757143
TI  - Calcium-channel blockers: managing uncertainty.

PMID- 8757144
TI  - Calcium-channel blockers and the clinician.

PMID- 8757145
TI  - Observational studies of drug safety.

PMID- 8757146
TI  - Metronidazole-resistant H pylori--of questionable clinical importance.

PMID- 8757147
TI  - Does location matter in ulnar and common peroneal nerve block?

PMID- 8757148
TI  - Glyceryl trinitrate for anal fissure.

PMID- 8757149
TI  - Collisions with animals.

PMID- 8757150
TI  - Calcium-channel blockade and incidence of cancer in aged populations.
AB  - BACKGROUND: Calcium-channel blockers can alter apoptosis, a mechanism for
      destruction of cancer cells. We examined whether the long-term use of calcium
      channel blockers is associated with an increased risk of cancer. METHODS: Between
      1988 and 1992 we carried out a prospective cohort study of 5052 people aged 71
      years or more and who lived in three regions of Massachusetts, Iowa, and
      Connecticut USA. Those taking calcium-channel blockers (n = 451) were compared
      with all other participants (n = 4601). The incidence of cancer was assessed by
      survey of hospital discharge diagnoses and causes of death. These outcomes were
      validated by the cancer registry in the one region where it was available.
      Demographic variables, disability, cigarette smoking, alcohol consumption, blood
      pressure, body-mass index, use of other drugs, hospital admissions for other
      causes, and comorbidity were all assessed as possible confounding factors.
      FINDINGS: The hazard ratio for cancer associated with calcium-channel blockers
      (1549 person-years, 47 events) compared with those not taking calcium-channel
      blockers (17225 person-years, 373 events) was 1.72 (95% CI 1.27-2.34, p =
      0.0005), after adjustment for confounding factors. A significant dose-response
      gradient was found. Hazard ratios associated with verapamil, diltiazem, and
      nifedipine did not differ significantly from each other. The results remained
      unchanged in community-specific analyses. The association between calcium-channel
      blockers and cancer was found with most of the common cancers. INTERPRETATION:
      Calcium-channel blockers were associated with a general increased risk of cancer
      in the study populations, which suggested a common mechanism. These observational
      findings should be confirmed by other studies.

PMID- 8757151
TI  - Ischaemic stroke and combined oral contraceptives: results of an international,
      multicentre, case-control study. WHO Collaborative Study of Cardiovascular
      Disease and Steroid Hormone Contraception.
AB  - BACKGROUND: The association between use of oral contraceptives (OCs) and cerebral
      infarction was established in studies from northern Europe and the USA during the
      1960s and 1970s. Since then, the constituents of hormonal OCs have changed and
      now contain lower doses of oestrogen and progestagen. Current recommendations
      restrict OC use to younger women who do not have other risk factors for
      cardiovascular disease. In this international study we assessed the risk of OC
      associated first stroke in women from Europe and other countries throughout the
      world. METHODS: In this hospital-based, case-control study, we assessed the risk
      of ischaemic stroke in association with current use of combined OCs in 697 cases,
      aged 20-44 years, and 1962 age-matched hospital controls in 21 centres in Africa,
      Asia, Europe, and Latin America. The diagnosis of ischaemic stroke was almost
      exclusively based on computed tomography (CT), magnetic resonance imaging (MRI),
      or cerebral angiography carried out within 3 weeks of the clinical event. All
      cases and controls were interviewed while in hospital with the same
      questionnaire, which included information on medical and personal history,
      details of lifetime contraceptive use, and blood-pressure measurements before the
      most recent episode of OC use. FINDINGS: The overall odds ratio of ischaemic
      stroke was 2.99 (95% CI 1.65-5.40) in Europe and 2.93 (2.15-4.00) in the non
      European (developing) countries. Odds ratios were lower in younger women and
      those who did not smoke, and less than 2 in women who did not have hypertension
      and who reported that their blood pressure had been checked before the current
      episode of OC use. By contrast, among current OC users with a history of
      hypertension, the odds ratio was 10.7 (2.04-56.6) in Europe and 14.5 (5.36-39.0)
      in the developing countries. In Europe, the odds ratio associated with current
      use of low-dose OCs (< 50 micrograms oestrogen) was 1.53 (0.71-3.31), whereas for
      higher-dose preparations it was 5.30 (2.56-11.0). In the developing countries,
      there was no significant difference between overall estimates of risk associated
      with use of low-dose or higher-dose OCs (3.26 [2.19-4.86] vs 2.71 [1.75-4.19]).
      This differential effect of dose in Europe and the developing countries is likely
      to be due to different levels of other risk factors among users of low-dose and
      higher-dose OCs in the two groups of countries. There was no significant increase
      in odds ratios with increasing duration of OC use among current users; odds
      ratios were not significantly increased after cessation of OC use.
      INTERPRETATION: The incidence of ischaemic stroke is low in women of reproductive
      age and any risk attributable to OC use is small. The risk can be further reduced
      if users are younger than 35 years, do not smoke, do not have a history of
      hypertension, and have blood pressure measured before the start of OC use. In
      such women OC preparations with low oestrogen doses may be associated with even
      lower risk.

PMID- 8757152
TI  - Haemorrhagic stroke, overall stroke risk, and combined oral contraceptives:
      results of an international, multicentre, case-control study. WHO Collaborative
      Study of Cardiovascular Disease and Steroid Hormone Contraception.
AB  - BACKGROUND: The risk of haemorrhagic stroke associated with use of oral
      contraceptives (OCs) is less well-established than that for ischaemic stroke. We
      assessed the risk of haemorrhagic stroke associated with current use of modern
      OCs as now used throughout the world. METHODS: In this WHO collaborative, case
      control study, we assessed the association between risk of haemorrhagic stroke
      and use of combined OCs in 1068 cases, aged 20-44 years, and 2910 age-matched
      controls. We also assessed risks for all strokes combined (haemorrhagic,
      ischaemic, and unclassified) based on 2198 cases and 6086 controls. FINDINGS:
      Overall, current use of combined OCs was associated with slightly increased risk
      of haemorrhagic stroke; the increase was significant in the developing countries
      (odds ratio 1.76 [95% CI 1.34-2.30]) but not in Europe (1.38 [0.84-2.25]). Use of
      OCs in women younger than 35 years did not affect risk of haemorrhagic stroke in
      either group of countries, whereas in women aged older than 35 years, odds ratios
      were greater than 2. Women who were current users of OCs and had a history of
      hypertension (detected before current episode of OC use, but not during
      pregnancy) had a substantially increased risk (ten-fold to 15-fold) of
      haemorrhagic stroke compared with women who did not use OCs and had no history of
      hypertension. Odds ratios among current OC users who were also current cigarette
      smokers were greater than 3. In both groups of countries, past use of OCs, dose
      of oestrogen, and dose and type of progestagen had no effect on risk, and risks
      were similar for subarachnoid and intracerebral haemorrhage. The odds ratios for
      any type of stroke associated with current use of low-dose (< 50 micrograms
      oestrogen) and higher-dose OCs were 1.41 (0.90-2.20) and 2.71 (1.70-4.32),
      respectively, in Europe and 1.86 (1.49-2.33) and 1.92 (1.48-2.50) in the
      developing countries. From these data we estimated that about 13% and 8% of all
      strokes in women aged 20-44 in Europe and the developing countries, respectively,
      are attributable to the use of OCs. INTERPRETATION: The risk of haemorrhagic
      stroke attributable to OC use is not increased in younger women and is only
      slightly increased in older women. The estimated excess risk of all stroke types
      associated with use of low-oestrogen and higher-oestrogen dose OCs in Europe was
      about two and eight, respectively, per 100 000 woman-years of OC use. However,
      findings need to be considered in the context of other risks and benefits
      associated with OC use, as well as those associated with the use of other forms
      of contraception.

PMID- 8757153
TI  - Ultrasonographic heel measurements to predict hip fracture in elderly women: the
      EPIDOS prospective study.
AB  - BACKGROUND: The ability of ultrasonographic measurements to discriminate between
      patients with hip fracture and age-matched controls has until now been tested
      mainly through cross-sectional studies. We report the results of a prospective
      study to assess the value of measurements with ultrasound in predicting the risk
      of hip fracture. METHODS: 5662 elderly women (mean age 80.4 years) had both
      baseline calcaneal ultrasonography measurements and femoral radiography (dual
      photon X-ray absorptiometry, DPXA) to assess their bone quality. Follow-up every
      4 months enabled us to identify incident fractures. 115 hip fractures were
      recorded during a mean follow-up duration of 2 years. FINDINGS: Low calcaneal
      ultrasonographic variables (obtained from measurements of broadband ultrasound
      attenuation by, and speed of sound through the bone) were able to predict an
      increased risk of hip fracture, with similar accuracy to low femoral bone mineral
      density (BMD) obtained by DPXA. The relative risk of hip fracture for 1 SD
      reduction was 2.0 (95% CI 1.6-2.4) for ultrasound attenuation and 1.7 (1.4-2.1)
      for speed of sound, compared with 1.9 (1.6-2.4) for BMD. After control for the
      femoral neck BMD, ultrasonographic variables remained predictive of hip fracture.
      The incidence of hip fracture among women with values above the median for both
      calcaneal ultrasound attenuation and femoral neck BMD was 2.7 per 1000 woman
      years, compared with 19.6 per 1000 woman-years for those with values below the
      median for both measures. INTERPRETATION: Ultrasonographic measurements of the os
      calcis predict the risk of hip fracture in elderly women living at home as well
      as DPXA of the hip does, and the combination of both methods makes possible the
      identification of women at very high or very low risk of fracture.

PMID- 8757154
TI  - Crohn's disease after in-utero measles virus exposure.
AB  - BACKGROUND: An epidemiological association between Crohn's disease and measles
      virus exposure in early life has been suggested in case-control studies. METHODS:
      To determine absolute risk estimates for in-utero measles virus exposure and
      Crohn's disease, maternity charts for all 25000 deliveries at University
      Hospital, Uppsala, between 1940-49 were reviewed: four cases of measles infection
      in the mother during pregnancy were identified. The children and two of their
      mothers were interviewed and case records reviewed. Three offspring had undergone
      multiple intestinal resections; tissue from these cases were examined by routine
      histology, and for measles-virus nucleoprotein antigen by immunohistochemistry
      and immunogold electronmicroscopy. FINDINGS: Three of the four children had
      Crohn's disease. In each the disease was preceded by recurrent, antibiotic
      resistant pneumonia. They had extensive ileal and colonic disease; two patients
      required intravenous feeding. The only offspring to have had measles as a child
      did not develop Crohn's disease. Measles virus antigen was detected in foci of
      granulomatous and lymphocytic inflammation in all children with Crohn's disease.
      INTERPRETATION: The data indicate that exposure of mothers to measles virus in
      utero is a risk factor for Crohn's disease in their children. Exposure at this
      time may lead to persistent infection, or modify the response to infection in
      later life, leading to persistence of measles virus.

PMID- 8757155
TI  - Diabetes, hypertension, and manic episodes.

PMID- 8757156
TI  - Zileuton.

PMID- 8757157
TI  - AIDS and the eyes.
AB  - The eye is affected in 50-75% of adult AIDS patients. This rate of ocular
      involvement is much higher than that in symptom-free HIV-seropositive patients,
      and seems to increase in incidence with severity of disease. These observations
      indicate that regular screening of HIV-positive patients is warranted to allow
      early identification of potential vision and life threatening disease.

PMID- 8757158
TI  - QED: quick and early diagnosis.

PMID- 8757159
TI  - Blood safety issues working group convened.

PMID- 8757160
TI  - Do calcium antagonists cause cancer?

PMID- 8757161
TI  - Antihypertensive drugs and risk of malignant diseases.

PMID- 8757163
TI  - Helicopter emergency medical service.

PMID- 8757162
TI  - Acute allergic reactions associated with azathioprine.

PMID- 8757164
TI  - Spongiform encephalopathies in mainland China.

PMID- 8757165
TI  - Resolution of autoimmune hepatitis after bone-marrow transplantation.

PMID- 8757166
TI  - Repeated episodes of shock due to food sensitisation.

PMID- 8757167
TI  - A new route from heart to lungs.

PMID- 8757168
TI  - Fluoroquinolone antibiotics in children with multidrug resistant typhoid.

PMID- 8757169
TI  - Association between pyoderma gangrenosum and psoriasis.

PMID- 8757170
TI  - Euthanasia, physician-assisted suicide, and persistent vegetative state.

PMID- 8757171
TI  - Euthanasia, physician-assisted suicide, and persistent vegetative state.

PMID- 8757172
TI  - Polymyalgia rheumatica.

PMID- 8757173
TI  - Melatonin and fragmented sleep patterns.

PMID- 8757174
TI  - Necrotising fasciitis in diabetics.

PMID- 8757175
TI  - Terfenadine-induced cholestatic hepatitis.

PMID- 8757176
TI  - Anthrax in southern India.

PMID- 8757177
TI  - Familial Mediterranean fever.

PMID- 8757178
TI  - Open-access echocardiography.

PMID- 8757179
TI  - Emergency hospital visits for asthma.

PMID- 8757180
TI  - Perpetrating myths.

PMID- 8757181
TI  - What is the role of thymidine phosphorylase in tumor angiogenesis.

PMID- 8757182
TI  - Hormones and prostate cancer: where do we go from here?

PMID- 8757183
TI  - Telomere integrity and cancer.

PMID- 8757184
TI  - Apoptosis provides new targets for chemotherapy.

PMID- 8757185
TI  - Raloxifene, retinoids, and lavender: "me too" tamoxifen alternatives under study.

PMID- 8757186
TI  - Endometrial cancers from tamoxifen are not more aggressive.

PMID- 8757187
TI  - Scientists figure out what makes HIV stick.

PMID- 8757188
TI  - Clinical niche sought for platelet-boosting drugs.

PMID- 8757189
TI  - Caloric restriction research comes of age.

PMID- 8757190
TI  - Clinicopathologic and prognostic significance of an angiogenic factor, thymidine
      phosphorylase, in human colorectal carcinoma.
AB  - BACKGROUND: Platelet-derived endothelial cell growth factor (PD-ECGF) is known to
      promote the development of new blood vessels, which are fundamental to tumor
      growth and metastasis. We previously found that thymidine phosphorylase
      (dThdPase) and PD-ECGF are the same protein. PURPOSE: We retrospectively examined
      the expression of dThdPase in primary colorectal carcinomas, its association with
      angiogenesis and clinicopathologic findings, and its prognostic value. METHODS:
      Tissues were obtained from the tumors of 163 patients whose colorectal carcinomas
      were completely removed by surgery. Microvessels assessed by immunostaining
      endothelial cells for factor VIII were counted on a 400x field in the most active
      areas of neovascularization within the tumor. We purified the monoclonal antibody
      against dThdPase and studied the expression of dThdPase in the same serial
      sections used for the detection of factor VIII. Those who carried out microvessel
      counting and dThdPase expression assessment had no knowledge of clinicopathologic
      findings. The significance of dThdPase in the prognosis of patients with
      colorectal carcinomas was also examined in the survival analysis of mortality
      follow-up data covering the period between 1984 through 1991. Reported P values
      are from two-sided tests of statistical significance. RESULTS: The mean
      microvessel count (+/- standard deviation) in dThdPase-positive colorectal
      carcinoma specimens (17.5 +/- 7.2) was higher (P < .001) than that in dThdPase
      negative carcinoma specimens (9.3 +/- 5.5). The dThdPase positivity was in
      accordance with the microvessel count. dThdPase positivity showed highly
      significant statistical associations with tumor size, extent of invasion, lymph
      node metastasis, lymphatic invasion, and venous invasion. Cox regression analysis
      revealed that dThdPase expression was prognostic for poor disease outcome after
      adjustment for Dukes' stage and microvessel count. CONCLUSIONS: These findings
      suggest that higher levels of dThdPase expression in colorectal carcinomas are
      associated with more extensive angiogenesis, poor clinical and laboratory
      findings, and unfavorable clinical outcome. IMPLICATIONS: Inhibition of dThdPase
      in human colorectal carcinomas might improve prognosis for some patients.

PMID- 8757191
TI  - Prospective study of sex hormone levels and risk of prostate cancer.
AB  - BACKGROUND: Sex steroids, particularly androgens, have been implicated in the
      pathogenesis of prostate cancer. Data from previous studies comparing circulating
      hormone levels in men with and without prostate cancer are difficult to
      interpret, since the studies were limited in size, hormone levels were analyzed
      in blood drawn after the diagnosis of cancer, nonrepresentative control subjects
      were used, and hormone and hormone-binding protein levels were not simultaneously
      adjusted. PURPOSE: We conducted a prospective, nested case-control study to
      investigate whether plasma hormone and sex hormone-binding globulin (SHBG) levels
      in healthy men were related to the subsequent development of prostate cancer.
      METHODS: Among participants in the Physicians' Health Study who provided plasma
      samples in 1982, we identified 222 men who developed prostate cancer by March
      1992. Three hundred ninety control subjects, matched to the case patients on the
      bases of age, smoking status, and length of follow-up, were also identified.
      Immunoassays were used to measure the levels of total testosterone,
      dihydrotestosterone (DHT), 3 alpha-androstanediol glucuronide (AAG), estradiol,
      SHBG, and prolactin in the stored (at -82 degrees C) plasma samples. Correlations
      between individual hormone levels and between hormone levels and SHBG in the
      plasma of control subjects were assessed by use of Spearman correlation
      coefficients (r). Odds ratios (ORs) and 95% confidence intervals (CIs) specifying
      the prostate cancer risk associated with quartile levels of individual hormones,
      before and after adjustment for other hormones and SHBG, were calculated by use
      of conditional logistic regression modeling. Reported P values are two-sided.
      RESULTS: No clear associations were found between the unadjusted levels of
      individual hormones or SHBG and the risk of prostate cancer. However, a strong
      correlation was observed between the levels of testosterone and SHBG (r = .55),
      and weaker correlations were detected between the levels of testosterone and the
      levels of both estradiol (r = .28) and DHT (r = .32) (all P < .001). When hormone
      and SHBG levels were adjusted simultaneously, a strong trend of increasing
      prostate cancer risk was observed with increasing levels of plasma testosterone
      (ORs by quartile = 1.00, 1.41, 1.98, and 2.60 [95% CI = 1.34-5.02]; P for trend =
      .004), an inverse trend in risk was seen with increasing levels of SHBG (ORs by
      quartile = 1.00, 0.93, 0.61, and 0.46 [95% CI = 0.24-0.89]; P for trend = .01),
      and a non-linear inverse association was found with increasing levels of
      estradiol (ORs by quartile = 1.00, 0.53, 0.40, and 0.56 [95% CI = 0.32-0.98]; P
      for trend = .03). No associations were detected between the levels of DHT or
      prolactin and prostate cancer risk; for AAG, a marker of 5 alpha-reductase
      activity, only suggestive evidence of a positive association was found. The
      results were essentially unchanged when case patients diagnosed within 4 years of
      plasma collection, case patients diagnosed with localized (i.e., nonaggressive)
      disease, or control subjects with elevated prostate serum antigen levels (> 2.5
      ng/mL) were excluded from the analyses. CONCLUSIONS: High levels of circulating
      testosterone and low levels of SHBG-both within normal endogenous ranges-are
      associated with increased risks of prostate cancer. Low levels of circulating
      estradiol may represent an additional risk factor. Circulating levels of DHT and
      AAG do not appear to be strongly related to prostate cancer risk.

PMID- 8757192
TI  - Case-control study of endogenous steroid hormones and endometrial cancer.
AB  - BACKGROUND: It has been suggested that identified risk factors for endometrial
      cancer operate through a single etiologic pathway, i.e., exposure to relatively
      high levels of unopposed estrogen (estrogen in the absence of progestins). Only a
      few studies, however, have addressed this issue directly. PURPOSE: We assessed
      the risk of developing endometrial cancer among both premenopausal and
      postmenopausal women in relation to the circulating levels of steroid hormones
      and sex hormone-binding globulin (SHBG). The independent effect of hormones was
      assessed after adjustment for other known risk factors. METHODS: The data used in
      the analysis are from a case-control study conducted in five geographic regions
      in the United States. Incident cases were newly diagnosed during the period from
      June 1, 1987, through May 15, 1990. The case patients, aged 20-74 years, were
      matched to control subjects by age, race, and geographic region. The community
      control subjects were obtained by random-digit-dialing procedures (for subjects
      20-64 years old) and from files of the Health Care Financing Administration (for
      subjects > or = 65 years old). Additional control subjects who were having a
      hysterectomy performed for benign conditions were obtained from the participating
      centers. Women reporting use of exogenous estrogens or oral contraceptives within
      6 months of interview were excluded, resulting in 68 case patients and 107
      control subjects among premenopausal women and 208 case patients and 209 control
      subjects among postmenopausal women. The hormone analyses were performed on blood
      samples obtained from case patients or from hysterectomy control subjects before
      surgery. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated
      by use of an unconditional logistic regression analysis after we controlled for
      matching variables and potential confounders. All P values were two-sided.
      RESULTS: High circulating levels of androstenedione were associated with 3.6-fold
      and 2.8-fold increased risks among premenopausal and postmenopausal women,
      respectively, after adjustment for other factors (P for trend = .01 and < .001,
      respectively). Risks related to other hormone fractions varied by menopausal
      status. Among postmenopausal women, a reduced risk was associated with high SHBG
      levels and persisted after adjustment was made for obesity and other factors (OR
      = 0.51; 95% CI = 0.27-0.95). High estrone levels were associated with increased
      risk (OR = 3.8; 95% CI = 2.2-6.6), although adjustment for other risk factors
      (particularly body mass index) diminished the effect (OR = 2.2; 95% CI = 1.2
      4.4). Albumin-bound estradiol (E2), a marker of the bioavailable fraction, also
      remained an important risk factor after adjustment was made for other factors (OR
      = 2.0; 95% CI = 1.0-3.9). In contrast, high concentrations of total, free, and
      albumin-bound E2 were unrelated to increased risk in premenopausal women. In both
      premenopausal and postmenopausal groups, risks associated with obesity and fat
      distribution were not affected by adjustment for hormones. CONCLUSION: High
      endogenous levels of unopposed estrogen are related to increased risk of
      endometrial cancer, but their independence from other risk factors is
      inconsistent with being a common underlying biologic pathway through which all
      risk factors for endometrial cancer operate. IMPLICATIONS: Further research
      should focus on alternative endocrinologic mechanisms for risk associated with
      obesity and body fat distribution and for the biologic relevance of the increased
      risk associated with androstenedione in both premenopausal and postmenopausal
      disease.

PMID- 8757193
TI  - Elimination of neuroblastoma and small-cell lung cancer cells with an anti-neural
      cell adhesion molecule immunotoxin.
AB  - BACKGROUND: The development of immunotoxins has been hampered by difficulties,
      particularly in solid tumors, of finding appropriate target antigens and of
      linking sufficiently potent toxins. PURPOSE: We evaluated the tissue specificity
      of an immunotoxin, N901-blocked ricin (N901-bR), and assessed its potential for
      eliminating neural cell adhesion molecule (NCAM)-positive tumor cells in
      conditions appropriate for in vitro purging, prior to autologous stem cell
      transplantation, and its potential for myelosuppression. N901-bR consists of a
      monoclonal antibody (MAb), N901, directed against CD56, an antigen of the family
      of NCAMs, covalently linked to blocked ricin as the cytotoxic effector moiety.
      METHODS: The tissue specificity of the N901 MAb and the N901-bR immunotoxin was
      tested against a wide array of human tumor tissues and normal human tissues by
      immunohistochemical staining. The cytotoxic activity of N901-bR was tested
      against both small-cell lung cancer (SCLC) cells and neuroblastoma cells, either
      alone or among normal bone marrow mononuclear cells, and the efficacy of this
      treatment to specifically eliminate these cells was evaluated in a limiting
      dilution assay. In addition, normal bone marrow mononuclear cells were incubated
      with N901-bR, and the toxic effects of the immunotoxin on normal hematopoietic
      progenitors was evaluated. RESULTS: N901 and N901-bR exhibited specificity for
      several neoplasms of neuroectodermal origin, including SCLC and neuroblastoma.
      Staining of normal tissues was essentially limited to various neuroendocrine
      cells, cardiac muscle cells, and cells in peripheral nerve tissue. We observed a
      time- and dose-dependent elimination of tumor cells in vitro, with three logs
      (i.e., > 99.9%) of malignant cells being killed following only 5 hours of
      exposure to 10 nM N901-bR. Unconjugated N901 MAb specifically blocked the
      elimination of NCAM-positive cells by N901-bR, whereas neither an isotype-matched
      control MAb nor galactose (the ligand of native ricin) had any effect on the
      activity of the immunotoxin, confirming the specificity of its cytotoxic
      activity. Importantly, N901-bR used under optimal conditions for in vitro tumor
      cell depletion was not toxic to hematopoietic precursors. CONCLUSIONS: N901-bR
      has the properties required to target CD56, an antigen present not only on cells
      from a large number of cancers of neuroendocrine origin, but also on some
      important normal tissues. In addition, treatment with this immunotoxin results in
      the highly effective and specific elimination of neuroblastoma and SCLC cells and
      does not affect normal hematopoietic progenitors. IMPLICATIONS: N901-bR may have
      clinical utility for purging of neuroblastoma cells and SCLC cells before
      autologous stem cell transplantation. Further toxicology studies are warranted to
      assess the potential of N901-bR for in vivo administration.

PMID- 8757194
TI  - Platelet-derived endothelial cell growth factor in human colon cancer
      angiogenesis: role of infiltrating cells.
AB  - BACKGROUND: Development of new blood vessels is essential for tumor growth and
      metastasis and depends on the production of angiogenic factors by tumor and/or
      infiltrating cells. We previously showed that vascular endothelial growth factor
      (VEGF) expression and vessel count correlate with metastasis in human colon
      cancer. Although most tumors with high vessel counts express high levels of VEGF,
      some do not. Recently, platelet-derived endothelial cell growth factor (PD-ECGF),
      another potent angiogenic factor, has been reported to be expressed in colon
      cancer. PURPOSE: In this study, we examined the role of PD-ECGF in colon cancer
      angiogenesis and whether PD-ECGF is derived from the tumor or infiltrating cells.
      METHODS: Immunostaining for PD-ECGF was performed on 96 colon cancer specimens,
      some of which were previously stained for VEGF and factor VIII, a marker that is
      specific for endothelial cells. Double staining was done by using antibodies to
      PD-ECGF and to CD68 (macrophage specific) or CD3 (lymphocyte specific) to confirm
      which infiltrating cells produce PD-ECGF. Northern blot analysis for PD-ECGF
      messenger RNA (mRNA) was performed on four colon cancer specimens and
      corresponding normal colon mucosae (same patients) and four human colon cancer
      cell lines (KM12SM, SW620, HT29, and NCI-H508) to determine whether colon cancer
      epithelium expresses PD-ECGF. RESULTS: Immunohistochemical analysis demonstrated
      that PD-ECGF was expressed in infiltrating cells in most of the colon cancer
      specimens (80 [83%] of 96) but rarely in tumor epithelium (five [5%] of 96).
      Double staining demonstrated that infiltrating cells staining positive for both
      PD-ECGF and CD68 were more predominant than those staining positive for both PD
      ECGF and CD3. The intensity of staining for PD-ECGF in infiltrating cells
      correlated with vessel counts (Spearman's rank correlation coefficient (R) = .29;
      P = .004), but did not correlate with the intensity of VEGF staining (R = .176, P
      = .086) or metastasis (Mann-Whitney U test, P = .253). PD-ECGF staining intensity
      was higher in specimens with a high vessel count (> 50 at high magnification) and
      low VEGF-staining intensity (< or = 2+) than in specimens with a high vessel
      count (again, > 50) and high VEGF-staining intensity (3+). Northern blot analysis
      revealed that colon cancer specimens and normal mucosae expressed relatively high
      levels of PD-ECGF mRNA, whereas PD-ECGF mRNA transcripts were not detectable in
      colon cancer cell lines. CONCLUSIONS AND IMPLICATIONS: PD-ECGF expression in
      human colon cancer specimens is associated with vessel count and may be
      responsible for tumor vascularity in those tumors with low VEGF expression.
      Infiltrating cells expressing PD-ECGF may contribute to angiogenesis, thus
      providing an additional mechanism for tumor neovascularization.

PMID- 8757195
TI  - Development of retinoblastoma in the absence of telomerase activity.
AB  - BACKGROUND: The length and stability of telomeres (essential functional
      structures at the end of eukaryotic chromosomes) have been implicated in the
      control of cell lifespan. Most somatic cells lack telomerase, the enzyme that
      synthesizes telomeric DNA, and their telomeres shorten with cell division. Cells
      immortalized in vitro, on the other hand, express telomerase and maintain their
      telomeres. Telomerase activity has also been detected in the large majority of
      tumors from a variety of cancers. These observations have suggested that telomere
      maintenance is required for unlimited cell proliferation and that telomerase is a
      marker for cell immortality in vitro and in vivo. PURPOSE: We investigated
      whether telomerase is activated during the development of retinoblastoma. This is
      a childhood eye cancer associated with a limited number of mutations in an
      embryonic tissue and thus likely to develop in cells that have long telomeres.
      The ease of detection of retinoblastoma makes it possible to screen relatively
      small tumors before extensive proliferation of the malignant cells. METHODS: We
      measured telomerase activity in 34 samples of retinoblastoma, four retinoblastoma
      derived cell lines, and six cell lines derived from other cancers. Only three of
      the cell lines from other cancers expressed the retinoblastoma protein.
      Telomerase activity was assayed by a polymerase chain reaction protocol in
      extracts prepared from tumors or cell lines. The level of enzyme activity in cell
      extracts was quantified at several protein concentrations and expressed relative
      to that in a positive control, after normalization for the amount of protein.
      Telomere length was measured by Southern blot hybridization of genomic DNA with a
      telomere-specific probe. Average values of telomere length in telomerase-positive
      and telomerase-negative tumors and in cell lines were compared by two-sided, two
      sample Student's t test. RESULTS: No telomerase activity was detected in 17 (50%)
      of 34 retinoblastomas. Assays of cell lines derived from other cancers revealed
      no association between the presence or the level of the enzyme activity and the
      expression of the retinoblastoma protein. Telomeres were significantly longer in
      telomerase-negative tumors than in telomerase-positive tumors (P = .0008).
      CONCLUSIONS: Our results indicate that retinoblastoma can develop when telomeres
      are still relatively long and in the absence of telomerase. Telomerase activity
      associated with short telomeres is, however, observed in 50% of the
      retinoblastomas and in retinoblastoma-derived cell lines. IMPLICATIONS:
      Telomerase may not be a marker for acquisition of the malignant phenotype in the
      case of tumors that are derived from cells with long telomeres and that are
      associated with a low number of mutations.

PMID- 8757196
TI  - Race and the incidence of cigarette smoking among adolescents in the United
      States.

PMID- 8757197
TI  - Re: Reductase enzyme expression across the National Cancer Institute tumor cell
      line panel: correlation with sensitivity to mitomycin C and E09.

PMID- 8757198
TI  - Management of chronic pain. Part II.
AB  - Chronic pain is associated with substantial psychosocial and economic stress
      coupled with functional loss and various levels of vocational dysfunction. The
      role of a pain center is to focus on chronic pain in a multidisciplinary,
      comprehensive manner, providing the patient with the most effective opportunity
      to manage his or her chronic disease syndrome. This article focuses on methods to
      manage many types of chronic pain and describes a broad range of pharmacologic
      and non-pharmacologic interventions and options available to the patient. Part I
      of this two-part monograph described pharmacotherapeutic interventions and
      regional nerve blocks. Part II focuses on psychologic assessment and treatment
      and physical therapy. A multimodal management strategy offers patients the
      greatest improvement potential for specific chronic pain syndromes. Cognitive and
      behavioral therapies and physical therapies are described. This combination of
      therapies may provide patients with the skills and knowledge needed to increase
      their sense of control over pain. The integration of appropriate
      pharmacotherapeutic regimens, neural blockades, physical therapy, and psychologic
      techniques maximizes the patient's effectiveness in dealing with chronic pain.
      Three case studies are presented in Part II.

PMID- 8757199
TI  - "Hidden" allergens in foods.

PMID- 8757200
TI  - Theophylline's effect on neutrophil function and the late asthmatic response.
AB  - BACKGROUND: The decrement in lung function associated with the late asthmatic
      response after allergen challenge is believed to be mediated by an inflammatory
      response in the airways. Theophylline has been shown to inhibit the late
      asthmatic response, but the mechanisms are not clear. OBJECTIVE: The study was
      designed to determine whether theophylline would inhibit the late asthmatic
      response by reducing neutrophil activation and subsequent superoxide production.
      METHODS: Twelve subjects with asthma underwent treatment in this double-blind,
      randomized, crossover study. Each subject received theophylline and placebo in
      random order in two treatment periods of 3 weeks each. Each treatment period was
      followed by an allergen challenge and blood neutrophil function analysis.
      RESULTS: At therapeutic levels theophylline increased FEV1 at baseline and during
      the allergen challenge and increased the percentage suppression of neutrophil
      superoxide production by adenosine. CONCLUSION: Theophylline improved pulmonary
      function at baseline and during an allergen challenge, in part perhaps, by
      increasing the neutrophil's response to feedback inhibition by adenosine.
      However, theophylline did not decrease the severity and duration of the late
      asthmatic response.

PMID- 8757201
TI  - Allergen-specific IgE levels and mite allergen exposure in children with acute
      asthma first seen in an emergency department and in nonasthmatic control
      subjects.
AB  - BACKGROUND: Sensitization to allergens has been shown to be a risk factor for
      adults with acute asthma first seen in the emergency department. OBJECTIVE: The
      purpose of this study was to evaluate the prevalence of specific IgE to common
      aeroallergens in children with asthma first seen in the emergency department and
      in control subjects. METHODS: Fifty-four children, aged 3 to 16 years (mean age,
      8.34 years) who visited the emergency department for treatment of acute
      bronchospasm or other illness, were evaluated. Specific IgE to seven common
      aeroallergens and four common storage mites was determined. Group I consisted of
      29 patients who had acute bronchospasm and histories of recurrent asthma. Group
      II consisted of 25 control subjects who had no clinical history of atopic
      disease. Group I and II were compared for differences in the prevalence of
      positive RAST responses to the 11 allergens tested. Dust samples were collected
      from 17 homes of subjects in group I and from 13 homes of subjects in group II
      and were analyzed for levels of Der p 1 and Der f 1. RESULTS: Statistically
      significant differences in the prevalence of positive RAST results between groups
      I and II were found in response to: Dermatophagoides pteronyssinus, 89.6% versus
      36% (p = 0.0001); Blattella germanica, 45.8% versus 9.5% (p = 0.018); Alternaria
      tenuis, 44.8% versus 4% (p = 0.001); and the storage mites Aleuroglyphus ovatus,
      39.2% versus 4% (p = 0.002); Blomia tropicalis, 42.8% versus 0% (p = 0.0002);
      Chortoglyphus arcuatus, 46.4% versus 0% (p = 0.0001); and Lepidoglyphus
      destructor, 32.1% versus 0% (p = 0.0019). Mean specific IgE levels, expressed as
      percent of the total counts bound, were significantly higher in group I compared
      with group II only in response to D. pteronyssinus, 21.9% versus 2.1% (mean
      percent of total counts bound) (p = 0.0001). Analysis of dust samples revealed no
      significant differences between the two groups, except for a higher concentration
      of Der f 1 in the sofas of subjects in group II. CONCLUSION: Sensitization to D.
      pteronyssinus, storage mites, and, to a lesser extent, to A. tenuis and B.
      germanica is associated with acute childhood asthma that requires emergency
      treatment in Florida.

PMID- 8757202
TI  - An economic evaluation of short-term inpatient rehabilitation for children with
      severe asthma.
AB  - BACKGROUND: The cost of asthma care in the United States in 1990 has been
      estimated to be 6.2 billion dollars. The greatest proportion is due to hospital
      care. OBJECTIVE: We report changes in estimated medical charges of 59 children
      with severe asthma 1 year before inpatient rehabilitation and over a 4-year
      follow-up period. METHODS: Asthma resource use (e.g., hospital, physician,
      medication) was identified before and after inpatient rehabilitation. Estimated
      charges were assigned. This was done retrospectively for the 1-year period before
      rehabilitation, prospectively during rehabilitation, and over a 4-year follow-up
      period. Patients served as their own controls. There was no control group.
      RESULTS: When median asthma resource use 1 year before rehabilitation was
      compared with that during the first, second, third, and fourth years of follow
      up, there was a reduction in median hospitalization and median emergency care.
      Compared with mean total medical charges the year before rehabilitation,
      reductions in mean total medical charges were 56.7% at the completion of the
      first year (excluding charges for rehabilitation), 70.5% at second year, 74.6% at
      third year, and 77.5% at fourth year. Over the 4-year postrehabilitation period,
      the discounted cumulative net savings was $29,605. The discounted cumulative net
      savings surpassed the mean rehabilitation charge during the early months of the
      fourth year of the postrehabilitation period. CONCLUSION: Inpatient
      rehabilitation was significantly associated with a reduction in estimated total
      medical charges over a 4-year follow-up period.

PMID- 8757203
TI  - Once daily intranasal fluticasone propionate (200 micrograms) reduces nasal
      symptoms and inflammation but also attenuates the increase in bronchial
      responsiveness during the pollen season in allergic rhinitis.
AB  - BACKGROUND: Fluticasone propionate aqueous nasal spray, a new topical
      corticosteroid, has been proved to be an effective treatment for seasonal
      allergic rhinitis. OBJECTIVES: We studied the effect of fluticasone propionate on
      nasal symptoms, circulating eosinophils, and nasal inflammation in patients with
      seasonal allergic rhinitis after high-load pollen exposure. Moreover, we examined
      its efficacy in preventing the increase in bronchial responsiveness to
      methacholine (PD20) during the pollen season. METHODS: We conducted a double
      blind, placebo-controlled, parallel-group study in patients who had a history of
      allergic rhinitis in response to pollens of grass and Parietaria species and were
      living in northern Italy. After a run-in period of 2 weeks, 24 patients were
      treated with fluticasone propionate (200 micrograms, once daily), and 26 patients
      received matched placebo for 6 weeks, starting from the beginning of the pollen
      season. Assessment of efficacy was based on scores of daily nasal symptoms. Nasal
      lavage was performed at the end of the season, and differential cell count was
      expressed as percent of total cells. PD20 methacholine was measured at the
      beginning and end of the season and after the season had ended. RESULTS:
      Fluticasone propionate significantly reduced nasal obstruction, itching, and
      rhinorrhea. Eosinophils in blood (p < 0.01) and nasal lavage (p < 0.001) were
      also reduced. Moreover, fluticasone significantly attenuated the decrease in mean
      PD20 methacholine (from 1.95 to 0.89 mg) compared with placebo (from 1.38 to 0.37
      mg: p < 0.01). After the season, no difference in PD20 methacholine was found
      between treatment groups. CONCLUSIONS: The results of this study indicate that
      fluticasone propionate is effective in decreasing nasal symptoms and eosinophil
      inflammation in patients with seasonal allergic rhinitis after high-load pollen
      exposure. Our results also demonstrate that treatment with fluticasone propionate
      partially prevents the increase in bronchial responsiveness provoked by the
      inhalation of seasonal pollens in allergic rhinitis.

PMID- 8757204
TI  - Increased sensitivity to bradykinin among African Americans.
AB  - BACKGROUND: Angioedema is a potentially life-threatening side effect of
      angiotensin-converting enzyme (ACE) inhibitors. Although the mechanism of
      angioedema is not certain, bradykinin has been implicated in its pathogenesis.
      Compared with Caucasians, African Americans are at an increased risk of ACE
      inhibitor-associated angioedema, independent of ACE inhibitor dose or concurrent
      medications. Because urinary kallikrein levels are decreased in African Americans
      with hypertension, we hypothesized that endogenous bradykinin levels may be
      decreased in African Americans and that they therefore may be more sensitive to
      ACE inhibitor-induced increases in bradykinin or to exogenous bradykinin.
      OBJECTIVE: To test this hypothesis, we measured the wheal response to intradermal
      injection of bradykinin in salt-replete hypertensive and normotensive African
      Americans and Caucasians. METHODS: Two doses of bradykinin, 1 microgram and 10
      micrograms, were administered on separate days in a randomized, double-blind
      fashion. RESULTS: Higher bradykinin dose (analysis of variance: F = 38.33, p <
      0.001), African American race (analysis of variance: F = 17.90, p < 0.001), and
      hypertension (analysis of variance: F = 4.37, p = 0.05) were all associated with
      an increased wheal response to bradykinin. CONCLUSION: These data provide
      additional support for racial differences in the kallikrein-kinin system and also
      implicate abnormalities of the tissue kallikrein-kinin system in essential
      hypertension.

PMID- 8757205
TI  - Exposure and sensitization to environmental allergen of predominantly Hispanic
      children with asthma in San Diego's inner city.
AB  - BACKGROUND: Environmental living conditions co-sorting with economic status may
      influence the disease morbidity rate of childhood asthma in ethnic minority urban
      poor populations. OBJECTIVES: This study was carried out to assess exposure and
      sensitization to environmental allergens in southeast San Diego children with
      current asthma-related symptoms and to determine the utility of environmental
      control measures. METHODS: Children, 9 to 12 years old, with current asthma
      related symptoms were identified and enrolled at four school sites. Skin prick
      testing with aeroallergens was performed, and allergen in collected dust (from
      mattresses, pillows, and bedroom carpets) was quantified by enzyme immunoassay.
      Environmental control instruction and products were provided. RESULTS: Of 41
      subjects who underwent skin testing, 51.2% were reactive to environmental
      allergens (39% to mite, 22% to cockroach, and 9.8% to cat). Mean allergen levels
      for sensitized subjects were: Der p 1 (11 subjects), 18,722 ng/gm dust; Der f 1
      (8 subjects), 5345 ng/gm dust; Fel d 1 (3 subjects), 214 ng/gm dust; Bla 1 (8
      subjects), 7.15 U/gm dust; and Bla 2 (8 subjects) 7.13 U/gm dust. Environmental
      allergen exposure levels were not significantly different between sensitized and
      nonsensitized subjects. Environmental control measures for mite exposure were
      completed in six homes of sensitized subjects. One month after treatment,
      allergen levels fell 91.2% for Der p 1, 98.9% for Der f 1, and 88.2% for Fel d 1.
      One year after treatment, mite and cat allergen levels remained low.
      Environmental control had no consistent impact on cockroach allergen levels.
      CONCLUSION: Environmental allergen sensitization and exposure may be cofactors
      contributing to increased disease severity in urban poor populations.

PMID- 8757206
TI  - The effect of inhaled albuterol in moderate to severe asthma.
AB  - BACKGROUND: Some recent clinical investigations suggest that regular use of
      inhaled bronchodilators may lead to deterioration in asthma control. OBJECTIVE:
      The purpose of this study was to evaluate the effect of albuterol dosing schedule
      on clinical outcome in subjects with moderate to severe stable asthma. METHODS:
      Seventeen adults were randomized to two 15-week treatment periods in a double
      blind crossover design. Throughout the study, subjects were instructed to take
      two inhalations four times daily from an unlabeled "test" canister. In the four
      times daily and as-needed (QID + PRN) period, this canister contained albuterol;
      in the as-needed (PRN) period, it contained placebo. A "rescue" albuterol
      canister was available for as-needed use at all times. Inhaler actuations from
      both the test and rescue canisters were electronically recorded. Outcome measures
      included prednisone requirements, morning and evening symptoms and peak
      expiratory flow rates, total and nighttime rescue albuterol use, and asthma
      specific quality of life. RESULTS: The two treatment periods did not differ in
      symptoms, nighttime albuterol use, or asthma quality of life. During the QID+PRN
      period both morning and evening peak expiratory flow rates were significantly
      higher (p < 0.01 and 0.001, respectively) and total rescue use of albuterol was
      significantly less (p < 0.05) than the PRN period. Days on prednisone tended to
      be lower in the regular dosing period (p = 0.08). CONCLUSION: In our sample of
      patients with moderate to severe asthma, four times daily dosing of albuterol did
      not lead to deterioration of asthma control.

PMID- 8757207
TI  - Double-strength beclomethasone dipropionate (84 micrograms/spray) aqueous nasal
      spray in the treatment of seasonal allergic rhinitis.
AB  - BACKGROUND: The use of intranasally administered corticosteroid sprays is an
      established treatment option for seasonal allergic rhinitis. METHODS: In this
      double-blind, placebo-controlled, multicenter study, 438 patients with moderate
      to severe symptoms of seasonal allergic rhinitis were treated for 4 weeks with
      double-strength beclomethasone dipropionate (BDP) aqueous nasal spray (84
      micrograms/spray: BDP-ds), once daily; regular-strength BDP (42 micrograms/spray:
      BDP-rs), twice daily; high-strength BDP (336 micrograms/spray: BDP-hs), once
      daily; or placebo. BDP-hs was included as a safety comparison group. All
      treatments were given as two sprays per nostril. RESULTS: Physician-rated nasal
      symptom scores were significantly improved in all three active treatment groups
      compared with those of the placebo group within the initial 3 days of treatment.
      Improvement was maintained throughout the 4-week treatment period. BDP-ds and BDP
      rs were equivalent at all time points. The BDP-ds, BDP-rs, and BDP-hs groups had
      greater numbers of patients with a good or excellent therapeutic response at end
      point than the placebo group. All treatments were well-tolerated, and no
      unexpected adverse events were reported. No effects on laboratory evaluations or
      vital signs were evident for any treatment group. CONCLUSIONS: The results of
      this study show that BDP-ds given once a day and BDP-rs given twice a day in the
      same total daily dose are comparably safe and effective in the treatment of
      patients with seasonal allergic rhinitis.

PMID- 8757208
TI  - Improvement of quality of life by treatment with cetirizine in patients with
      perennial allergic rhinitis as determined by a French version of the SF-36
      questionnaire.
AB  - BACKGROUND AND AIM: Perennial allergic rhinitis impairs social life, but it is
      not known whether quality of life may be improved when patients are treated with
      an H1-blocker. A randomized, double-blind, placebo-controlled study was carried
      out with cetirizine to assess the effect of this drug on quality of life.
      METHODS: Two hundred seventy-four patients with perennial allergic rhinitis were
      tested. Quality of life was measured by using the Medical Outcome Study Short
      Form Health Survey (SF-36) questionnaire. After a 2-week run-in period,
      cetirizine, 10 mg once daily, (136 patients) or placebo (138 patients) was given
      for the next 6 weeks. The SF-36 questionnaire was administered after the run-in
      period (at the start of treatment) and after 1 and 6 weeks of treatment. Symptom
      medication scores were measured daily during the study. RESULTS: After the run-in
      period (baseline), there were no significant differences between the cetirizine
      and placebo groups in terms of symptoms or quality-of-life scores. After 6 weeks
      of treatment, percentage of days without rhinitis or with only mild rhinitis
      symptoms was significantly greater in the cetirizine group in comparison with the
      placebo group (p < 0.0001, Mann-Whitney U test). All of the nine quality-of-life
      dimensions were significantly improved (from p = 0.01 to p < 0.0001, Mann-Whitney
      U test) after 1 and 6 weeks of cetirizine treatment compared with placebo. There
      was no improvement in the placebo group. CONCLUSIONS: This study is the first to
      demonstrate that an H1-blocker, cetirizine, can improve quality of life for
      patients with perennial allergic rhinitis.

PMID- 8757209
TI  - A placebo-controlled multicenter study of auranofin in the treatment of patients
      with corticosteroid-dependent asthma. Auranofin Multicenter Drug Trial.
AB  - BACKGROUND: Previous clinical studies have demonstrated that injectable gold
      salts and the oral gold compound, auranofin, possess significant steroid-sparing
      effects in the treatment of asthma. OBJECTIVES: The objectives of this
      investigation were to determine whether auranofin could reduce oral
      corticosteroid requirements and to evaluate the safety of auranofin in the
      treatment of chronic corticosteroid-dependent asthma. METHODS: Patients with
      asthma were eligible if they required at least 10 mg of prednisone per day for
      control and prevention of asthma exacerbations. Two hundred seventy-nine patients
      with chronic corticosteroid-dependent asthma (requiring > or = 10 mg/day) were
      randomized to receive auranofin, 3 mg twice daily, or placebo during an 8-month
      clinical trial, which was divided into three phases including: a 4-week baseline
      period (phase I), a 6-month double-blind treatment and steroid reduction period
      (phase II), and a 4-week posttreatment observation period during which steroid
      and auranofin doses or placebo doses were maintained at levels achieved by the
      end of phase II (phase III). The primary efficacy variable was "therapeutic
      success" or reduction of daily corticosteroid use by 50% or more. RESULTS: The
      proportion of patients in the auranofin group achieving therapeutic success (41%)
      was significantly higher than that in the placebo group (27%) (p = 0.01). This
      effect was greatest in patients requiring 10 to 19 mg of oral prednisone per day
      at baseline (p < 0.001). In all treated patients, including those who did and did
      not complete the trial, significant reduction (> or = 50% of baseline) in oral
      corticosteroid dosage was achieved in the auranofin group (60%) compared with the
      placebo group (32%) (p < 0.001). There were no significant differences between
      treatment groups in symptoms, concomitant medication use, or lung function. Mean
      serum total IgE levels decreased significantly from baseline in the auranofin
      group (-44.63 IU/ml) compared with the placebo group (p = 0.001).
      Gastrointestinal and cutaneous adverse events were greater in the auranofin
      group. CONCLUSIONS: Auranofin demonstrated a steroid-sparing effect without
      concomitant worsening of symptoms or lung function and appeared to be more
      effective in patients dependent on 10 to 19 mg of prednisone per day. Therefore
      this study has demonstrated that auranofin is useful as a steroid-sparing agent
      in the treatment of chronic corticosteroid-dependent asthma.

PMID- 8757210
TI  - A prospective, controlled study showing that rubber gloves are the major
      contributor to latex aeroallergen levels in the operating room.
AB  - BACKGROUND: Although protocols have been published for reducing natural rubber
      latex exposure in medical environments, there are no objective data documenting
      their effectiveness. OBJECTIVE: We prospectively studied the impact of a single
      intervention, substitution of low-allergen-containing latex gloves for high
      allergen-containing latex gloves, on latex aeroallergen levels in a single
      operating room (OR). METHODS: We sampled OR air on 52 consecutive days, including
      33 surgery days and 19 nonsurgery days. On each surgery day all personnel wore
      either high-allergen gloves (n = 18 days) or low-allergen gloves (n = 15 days).
      Latex aeroallergen levels (in nanograms per cubic meter) and extractable latex
      glove allergen contents (in allergen units per milliliter) were measured by
      inhibition immunoassays. An on-site study monitor recorded the number of gloves
      used, the total time spent by all patients in the OR each day (OR time), and the
      total time of all procedures for each day (operating procedure time). RESULTS:
      Latex aeroallergen levels during low-allergen glove use days (mean, 1.1 ng/m3;
      median, 0.9 ng/m3; range, 0.1 to 3.5 ng/m3) were significantly lower than on high
      allergen glove use days (mean, 13.7 ng/m3; median, 7.7 ng/m3; range, 2.2 to 56.4
      ng/m3) (p < 0.001) but not significantly different from that on nonsurgery days
      (mean, 0.6 ng/m3; median, 0.3 ng/m3; range, 0.1 to 3.6 ng/m3). Latex aeroallergen
      levels were strongly correlated with the total number of gloves used on
      designated high-allergen glove days (r = 0.66, p = 0.003). There was no
      appreciable day-to-day carryover of latex aeroallergen. CONCLUSIONS: The
      substitution of low-allergen-containing latex gloves for high-allergen-containing
      latex gloves can reduce levels of latex aeroallergen by more than 10-fold in an
      OR environment.

PMID- 8757211
TI  - Cloning and expression in yeast Pichia pastoris of a biologically active form of
      Cyn d 1, the major allergen of Bermuda grass pollen.
AB  - BACKGROUND: Pollen of grasses, such as Bermuda grass (Cynodon dactylon),
      represent a major cause of type I allergy. OBJECTIVE: In this report we attempted
      to clone and express a biologically active form of recombinant Cyn d 1, the major
      allergen of Bermuda grass pollen, in the yeast Pichia pastoris. METHODS: Clones
      encoding Cyn d 1 were isolated by screening a Bermuda grass pollen complementary
      DNA library with specific monoclonal antibodies and by polymerase chain reaction
      amplification. Recombinant Cyn d 1 was expressed in Escherichia coli and yeast.
      The expressed proteins were analyzed by Western blotting to assess binding to Cyn
      d 1-specific monoclonal antibodies and IgE from sera of patients allergic to
      Bermuda grass pollen. RESULTS: Two isoforms of Cyn d 1 were cloned. Recombinant
      Cyn d 1 expressed in bacteria bound two monoclonal antibodies raised against Cyn
      d 1 but was not recognized by IgE from sera of patients allergic to Bermuda grass
      pollen. Cyn d 1 expressed in yeast bound both the monoclonal antibodies and human
      IgE. CONCLUSION: An IgE-reactive Cyn d 1 was expressed in yeast but not in
      bacteria, suggesting that posttranslational modifications (e.g., glycosylation),
      which occur in eukaryotic cells such as yeast, are necessary for the production
      of a biologically active allergen.

PMID- 8757212
TI  - Early commitment to the eosinophil lineage by cultured human peripheral blood
      CD34+ cells: messenger RNA analysis.
AB  - Early hematopoietic progenitors expressing the CD34+ phenotype can be harvested
      from the peripheral blood of normal individuals. We have optimized the liquid
      culture of human CD34+ peripheral blood progenitors (PBPs) to achieve
      differentiation into a population of cells consisting almost entirely of
      eosinophil progenitors and maturing eosinophils. Growth of CD34+ PBPs for 28 days
      in the presence of the combination of IL-3, granulocyte-macrophage colony
      stimulating factor, and IL-5 resulted in an almost 250-fold increase in cell
      number, yielding a population that contained 83% maturing eosinophils. The
      residual population consisted of basophils and mast cells (3% by acidic toluidine
      blue staining, 15.2% by flow cytometric assay for binding to high-affinity IgE
      receptor) and immature cells. This provides an opportunity to examine the
      kinetics of the acquisition of specialized mature eosinophil characteristics
      during eosinophil differentiation. Several host-defense and bioactive proteins
      are found almost exclusively in eosinophil granules. In addition, stimulated
      eosinophils, like neutrophils, produce copious amounts of toxic oxygen radicals.
      We used our culture system and the sensitive technique of reverse-transcriptase
      polymerase chain reaction to analyze the kinetics of production of messenger RNA
      transcripts encoding several eosinophil proteins, including five eosinophil
      granule proteins and four subunit peptides of the superoxide-generating reduced
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in small numbers of
      differentiating eosinophils from peripheral blood CD34+ cells. Freshly isolated
      CD34+ PBPs contained transcripts for the ubiquitously present housekeeping
      protein phosphoglucokinase but contained no eosinophil granule protein
      transcripts and barely detectable amounts of some oxidase protein transcripts. On
      day 3 of culture, no cells recognizable by histochemical staining as eosinophils
      could be detected, but transcripts for all five eosinophil granule proteins were
      present. These transcripts increased several fold during the entire culture
      period. Similar kinetics were seen for all but one of the NADPH oxidase protein
      transcripts. However, transcripts for the p67phox NADPH oxidase protein were not
      detected until day 7, and functional oxidase activity did not appear until day
      12. From that point, oxidase activity increased dramatically over the culture
      period. These studies demonstrate that commitment of CD34+ PBPs to the eosinophil
      lineage occurs very early, by day 3, but that further events in differentiation
      must take place before the appearance of histologically staining eosinophil
      granules and acquisition of functional oxidase capacity.

PMID- 8757213
TI  - Comparative ultrastructural morphology of human basophils stimulated to release
      histamine by anti-IgE, recombinant IgE-dependent histamine-releasing factor, or
      monocyte chemotactic protein-1.
AB  - An ultrastructural analysis of human basophils stimulated with anti-IgE,
      recombinant histamine-releasing factor (rHRF), or monocyte chemotactic protein-1
      (MCP-1) (compared with unstimulated cells) was performed. Partially purified
      peripheral blood basophils were prepared for electron microscopy at time points
      known to precede histamine release and at half-maximum histamine release times
      for each secretagogue. Activation morphologies associated with stimulation
      included granule-vesicle attachments, piecemeal degranulation, anaphylactic
      degranulation, and uropod formation. These features were qualitatively similar in
      the stimulated samples. Quantitative differences were evident, however, when
      stimulated samples were compared with controls or at different time points after
      stimulation with a single agent or when individual secretagogues were compared.
      All stimulated samples differed quantitatively from the control samples. Rank
      orders for morphologic activation events revealed that the most effective trigger
      for anaphylactic degranulation was anti-IgE > MCP-1 > rHRF, whereas the most
      effective trigger for uropod formation was rHRF > anti-IgE > MCP-1. Rank orders
      for piecemeal degranulation and granule-vesicle attachments were the same: MCP-1
      > anti-IgE > rHRF. Important relationships among these anatomic events reveal
      that the development of motile configurations is not associated with the
      development of secretion morphologies and that piecemeal degranulation precedes
      and is inversely related to anaphylactic degranulation in stimulated samples.

PMID- 8757214
TI  - Cytokines directly induce degranulation and superoxide production from human
      eosinophils.
AB  - BACKGROUND: Cytokines are implicated in allergic diseases and can modulate
      effector functions of eosinophils stimulated by another agonist. However, little
      is known about the capacity of cytokines to directly trigger eosinophil
      degranulation. OBJECTIVES: We attempted to determine whether cytokines can
      directly induce degranulation and superoxide production from eosinophils.
      METHODS: Eosinophils from normal donors were incubated with various cytokines in
      albumin-coated tissue culture plates for 4 hours. To quantitate degranulation,
      the amounts of eosinophil-derived neurotoxin in supernatants were measured by
      radioimmunoassay. In addition, superoxide production was measured by superoxide
      dismutase-inhibitable reduction of cytochrome c. RESULTS: IL-5, IL-3, granulocyte
      macrophage colony-stimulating factor, tumor necrosis factor- alpha, and RANTES
      all induced eosinophil degranulation. Granulocyte-macrophage colony-stimulating
      factor was the most potent and induced eosinophil-derived neurotoxin release
      comparable to that induced by secretory IgA beads, one of the most potent
      secretagogues for eosinophils. In addition, IL-5 and tumor necrosis factor- alpha
      were synergistic in their induction of eosinophil degranulation. In contrast, IL
      1, IL-8, interferon- gamma, and macrophage inflammatory protein-1 alpha did not
      induce degranulation. Finally, IL-5, IL-3, granulocyte-macrophage colony
      stimulating factor, and tumor necrosis factor- alpha, but not RANTES, also
      induced superoxide production from eosinophils. CONCLUSIONS: Certain cytokines
      directly induce eosinophil degranulation and superoxide production in vitro.
      Therefore these cytokines may be important in the release of toxic granule
      proteins from eosinophils in allergic diseases.

PMID- 8757215
TI  - Studies of allergen extract stability: the effects of dilution and mixing.
AB  - BACKGROUND: However potent the allergy extracts provided by manufacturers, they
      are subject to deterioration with storage, especially after dilution or mixture
      with other extracts. OBJECTIVE: This study was performed to assess separately the
      deterioration during storage in allergen extract potency caused by dilution or by
      mixture with allergen extracts that have been reported to contain proteases.
      METHODS: To assess the effect of dilution, three serial 10-fold dilutions of cat,
      short ragweed, Bermuda grass, and Dermatophagoides farinae extracts were prepared
      alone or combined with other extracts. They were stored at 4 degrees C for 3 and
      12 months. To assess the effect of mixing with other extracts that have been
      reported to contain proteases, extracts of timothy grass, Bermuda grass, short
      ragweed, Russian thistle, white oak, box elder, D. farinae, and cat were stored
      alone or combined with one or more extracts of American cockroach, Alternaria
      spp., Cladosporium spp., Penicillium spp., and a house dust mite mix for 3 months
      at 4 degrees C. RESULTS: Bermuda grass, cat, and house dust mite extracts
      incurred significant loss of potency at all dilutions with storage. Short ragweed
      was stable at all dilutions. Potency of extracts of timothy grass, Bermuda grass,
      Russian thistle, white oak, box elder, and cat were all reduced by combination
      with one or more extracts potentially containing proteases. Only short ragweed
      and D. farinae, which was in a final concentration of 25% glycerin, were
      resistant. Alternaria extract was most frequently responsible for loss of
      potency, followed by cockroach and Cladosporium extracts. Combination with
      extracts of Penicillium and a house dust mite mix did not reduce the potency of
      any extract. CONCLUSIONS: Both dilution alone and mixture with extracts reported
      to contain proteases caused loss of potency of most extracts tested. Ragweed was
      uniquely resistant under both conditions of storage.

PMID- 8757217
TI  - Effect of nedocromil sodium on allergen-induced airway responses and changes in
      the quantity of airway smooth muscle in rats.
AB  - BACKGROUND: Allergen exposures induce growth of airway smooth muscle in the Brown
      Norway rat. OBJECTIVE: The purpose of the study was to examine the role of
      mediators associated with the early and late responses in the induction of airway
      smooth muscle growth. METHODS: Nedocromil sodium was administered to block early
      and late responses in ovalbumin-sensitized and ovalbumin-challenged rats
      undergoing single or multiple challenges (5 times at 5-day intervals) with
      ovalbumin. Airway smooth muscle was quantitated by morphometry on lungs removed 2
      days after the final challenge. RESULTS: Nedocromil sodium administered before
      ovalbumin challenge blocked both the early and late responses. When administered
      2 hours after ovalbumin challenge, it also blocked the late response. Rats
      undergoing challenge with aerosolized ovalbumin five times at 5-day intervals
      were also treated with nedocromil before (n = 10) or 2 hours after (n = 10) each
      ovalbumin inhalation, respectively. The quantity of airway smooth muscle
      standardized for size was greater after ovalbumin challenge (0.069 +/- 0.005)
      compared with saline controls (0.033 +/- 0.003, p < 0.005). Nedocromil
      significantly reduced the airway smooth muscle (0.036 +/- 0.003, p < 0.005) when
      administered before ovalbumin. However, the airway smooth muscle in rats that
      received nedocromil 2 hours after ovalbumin challenge (0.046 +/- 0.003), although
      lower than in ovalbumin-challenged rats (p < 0.01), was still significantly
      higher than in saline-treated rats (p < 0.05). CONCLUSIONS: Allergen-induced
      early responses, late responses, and airway inflammation are antagonized by
      nedocromil. The mediators of both the early and late responses contribute to
      allergen-induced airway smooth muscle growth, a process that can be prevented by
      administration of nedocromil.

PMID- 8757216
TI  - Effects of cyclosporin A and FK-506 on stem cell factor-induced histamine
      secretion and growth of human mast cells.
AB  - Stem cell factor (SCF) is a key regulator of human mast cells (MCs) and a
      potential mediator of allergy. In this study the effects of cyclosporin A (CSA)
      and FK-506, two potent immunosuppressive drugs, on SCF-dependent histamine
      release and growth of human MCs were analyzed. Preincubation of tissue MCs with
      CSA (3 micrograms/ml) resulted in inhibition of histamine release provoked by
      either recombinant human (rh) SCF (70.3% +/- 20.6% inhibition, p < 0.001) or anti
      IgE (76.7% +/- 21.9%, p < 0.001) or by rhSCF+ anti-IgE (77.4% +/- 13.9%, p <
      0.001). Almost the same inhibition was produced by FK-506 (rhSCF: 82.0% +/- 18.9%
      inhibition, p < 0.001; anti-IgE: 71.5% +/- 16.7%, p < 0.001; rhSCF+ anti-IgE:
      70.0% +/- 7.3%, p < 0.001). The effects of CSA and FK-506 on SCF-dependent
      release of histamine were dose-dependent (IC50: CSA, 1 to 10 ng/ml; FK-506, 0.3
      to 3 ng/ml). IC50 values about three to 10 times higher were found for MCs
      preincubated with rhSCF before anti-IgE activation, compared with anti-IgE or SCF
      alone. SCF-dependent differentiation of human MCs was analyzed in a long-term
      suspension culture system (n = 6). Unexpectedly, CSA and FK-506 were unable to
      suppress, but even enhanced SCF-dependent growth of MCs and formation of MC
      tryptase in long-term culture. Together, CSA and FK-506 inhibit SCF-dependent
      release of histamine from human MCs and even augment SCF-dependent growth of
      human MCs in long-term culture.

PMID- 8757218
TI  - Histamine and leukotriene C4 release in cutaneous mosquito-bite reactions.
AB  - BACKGROUND: Mosquito bites are known to sensitize persons, and the most common
      cutaneous reactions are immediate wheals and delayed bite papules. Anti-saliva
      IgE and IgG4 antibodies are common in mosquito-sensitive subjects, but mediator
      release in bite reactions is not known. METHODS: We used the microdialysis
      technique to measure in vivo histamine and leukotriene C4 release after bite
      challenges in six mosquito-sensitive subjects. One individual who was not
      sensitive to bites volunteered as a control subject. RESULTS: Three of the six
      mosquito-sensitive subjects had large wheals and showed clearly increased
      histamine concentrations 30 to 45 minutes after the bites. The histamine levels
      declined to baseline value within 2 hours; thereafter, one subject showed a
      second increase in histamine concentration. Four of the six mosquito-sensitive
      subjects showed increased leukotriene C4 concentrations, and this mediator seemed
      to be released somewhat later than histamine. CONCLUSIONS: The increased
      histamine and leukotriene C4 release observed in this study suggests that both
      mediators are involved in the early allergic response caused by mosquito bites.

PMID- 8757219
TI  - Involvement of endothelin in mononuclear phagocyte inflammation in asthma.
AB  - BACKGROUND AND AIM: Endothelin has bronchoconstrictive, vasoactive, and
      inflammatory properties and may be involved in the pathogenesis of asthma. We
      have studied the involvement of endothelin in asthma by examining its expression
      and release by mononuclear phagocytes obtained from 56 patients with asthma and
      32 control subjects and the activation of mononuclear phagocytes by endothelin.
      METHODS: Endothelin immunoreactivity was studied by using immunocytochemistry on
      monocytes and alveolar macrophages. Spontaneous and lipopolysaccharide-induced
      endothelin release from monocytes and alveolar macrophages was studied by
      radioimmunoassay. The proportion of intracellular endothelin was assessed after
      cell disruption by Triton (Union Carbide Corp., Bound Brook, N.J.). The release
      of fibronectin and tumor necrosis factor-alpha induced by endothelin was studied
      in alveolar macrophages by enzyme immunoassay. RESULTS: Endothelin
      immunoreactivity was significantly increased in cells from patients with asthma
      in comparison with those from the control group, but its release by alveolar
      macrophages was similar in both groups. Levels in the cell lysates and
      supernatants were similar for patients with asthma and normal subjects.
      Endothelin significantly increased the release of tumor necrosis factor-alpha and
      fibronectin by alveolar macrophages from normal subjects and patients with stable
      asthma, but it significantly decreased their release in patients with unstable
      asthma. CONCLUSION: This study suggests a role for endothelin in airway
      inflammation in asthma. Endothelin may act in a different fashion on alveolar
      macrophages, depending on the degree of stability of the disease.

PMID- 8757220
TI  - Increased urinary excretion of the prostaglandin D2 metabolite 9 alpha, 11 beta
      prostaglandin F2 after aspirin challenge supports mast cell activation in aspirin
      induced airway obstruction.
AB  - Prostaglandin (PG)D2 is a major product of arachidonic acid metabolism in
      pulmonary mast cells. We therefore attempted to determine whether measurement of
      the stable urinary metabolite of PGD2, 9 alpha, 11 beta-PGF2, could serve as a
      marker of mast cell activation in the lungs. A commercially available enzyme
      immunoassay was validated and found to be specific and sensitive when applied to
      unpurified urine. There was no diurnal variation in the levels of 9 alpha, 11
      beta-PGF2 in healthy volunteers. Morning baseline values of urinary 9 alpha, 11
      beta-PGF2 were measured in three groups--healthy volunteers (n = 9), patients
      with atopic asthma (n = 14), and aspirin-intolerant patients with asthma (n = 12)
      -and found to be very similar, 54 +/- 9, 62 +/- 6, and 71 +/- 15 ng/mmol
      creatinine, respectively (means +/- SEM). Urinary excretion of 9 alpha, 11 beta
      PGF2 was increased threefold immediately after allergen-induced
      bronchoconstriction in nine patients with atopic asthma. Bronchial challenge with
      inhaled lysine aspirin in eight aspirin-intolerant patients with asthma produced
      bronchoconstriction without extrapulmonary symptoms and was also followed by a
      significant increase in the urinary excretion of 9 alpha, 11 beta-PGF2. In
      addition, challenge with a higher dose of aspirin produced an even greater
      increase in urinary 9 alpha, 11 beta-PGF2, supporting dose-dependent release of
      PGD2 during aspirin-induced bronchoconstriction. In contrast, the postchallenge
      levels of urinary 9 alpha, 11 beta-PGF2 were not increased when
      bronchoconstriction was induced by histamine challenge in the aspirin-intolerant
      patients with asthma. The study confirms mast cell involvement in allergen
      induced bronchoconstriction and provides novel data, which strongly support the
      hypothesis that pulmonary mast cells are activated during aspirin-induced airway
      obstruction. It is finally suggested that measurement of urinary 9 alpha, 11 beta
      PGF2 with enzyme immunoassay may be used as a new noninvasive strategy to monitor
      mast cell activation in vivo.

PMID- 8757221
TI  - CD45 isoforms on human CD4+ T-cell subsets.
AB  - We have examined the level of surface expression and functional properties of
      leukocyte function associated antigen-1, very late antigen-4, and CD45 isoforms
      on a panel of human CD4+ T-cell clones representative of TH0, TH1, and TH2 cells.
      There were no qualitative differences in the expression of these antigens among
      the three types of CD4+ T-cell clones. However, CD45RB was the only CD45 isoform
      that provided a costimulatory signal in a solid-phase antibody-induced cellular
      proliferation assay. Additionally, the antigen-induced proliferative response of
      T-cell clones was inhibited by soluble anti-CD45RO and anti-CD45RB antibodies.
      Our results suggest that CD45 isoforms differentially provide costimulatory
      signals to T cells. However, the ability of each CD45 isoform to provide a
      costimulatory signal does not differ among the TH0, TH1, or TH2 T-cell
      populations.

PMID- 8757222
TI  - Farmer's lung: patients' IgG2 antibodies specifically recognize Saccharopolyspora
      rectivirgula proteins and carbohydrate structures.
AB  - Farmer's lung is a frequent form of extrinsic allergic alveolitis. In Europe and
      Northern America the main source of the antigenic components that induce farmer's
      lung is the bacterium Saccharopolyspora rectivirgula (Micropolyspora faeni). It
      remains unclear, however, which S. rectivirgula components are responsible for
      the disease. We approached these problems by investigating the serologic reaction
      of patients with farmer's lung and demonstrated specific binding of patients'
      IgG2 to S. rectivirgula antigens. No such antibodies were found in exposed,
      unaffected subjects. Thus IgG2 antibodies reacting with S. rectivirgula antigens
      are useful for the serologic diagnosis of patients with farmer's lung and for the
      isolation of disease-causing antigens. After separation of S. rectivirgula
      extract on concanavalin A-Sepharose (Pharmacia, Uppsala, Sweden), we found that
      approximately one third of the patients' IgG2 reactivity occurred with
      nonglycosylated proteins. Among these, we characterized two major acidic proteins
      with molecular weights of 12 and 30 kd, respectively, and with identical N
      terminal sequences. Approximately two thirds of the patients' IgG2 reactivity was
      observed against concanavalin A-binding glycoproteins that contained mainly
      glucose, mannose, and galactose residues. Deglycosylation of the concanavalin A
      bound fraction indicated that most of the IgG2 reactivity occurred with the
      carbohydrate components.

PMID- 8757223
TI  - Antibody response to unconjugated Haemophilus influenzae b and pneumococcal
      polysaccharide vaccines in children with recurrent infections.
AB  - BACKGROUND: Increasingly, antibody testing is being used to evaluate the status
      of humoral immunity in patients with recurrent infection and suspected
      immunodeficiency. In the past, we had been impressed that immunization with
      unconjugated Haemophilus influenzae b (uHib) vaccine provided useful information
      about the ability to produce antibody to polysaccharides and that the use of
      pneumococcal polysaccharide (PPS) vaccine frequently produced results that were
      difficult to interpret. OBJECTIVE: The study was carried out to compare antibody
      responsiveness to vaccination with uHib with the response seen after PPS
      vaccination. METHODS: Twenty children (ages, 2 to 13 years; 11 male) who were
      referred to our immunology clinic because of recurrent infections were immunized
      with both uHib vaccine and PPS vaccine. Nine children had previously received
      conjugated Hib vaccine. RESULTS: All 20 children either responded with a twofold
      or greater increase in antibody titer after uHib vaccine or had preimmunization
      antibody concentrations of greater than 400 nanograms antibody nitrogen per
      milliliter (ng Ab N/ml). All of the children responded to PPS-3 with
      postimmunization antibody concentrations greater than 400 ng Ab N/ml. Three
      children had an increase in titer to PPS-7 of less than twofold, seven did not
      have a twofold increase in titer to PPS-9, and 15 had an increase in titer to PPS
      14 of less than twofold. CONCLUSION: Unconjugated Hib vaccine is a potent
      immunogen in children over 2 years of age. Prior immunization with the conjugate
      vaccine did not prevent a response to unconjugated vaccine. Unconjugated Hib
      vaccine appears to be at least as immunogenic as PPS-3 when used as an assessment
      vaccine for evaluating antibody responsiveness.

PMID- 8757224
TI  - Independent anaphylaxis to cefazolin without allergy to other beta-lactam
      antibiotics.

PMID- 8757225
TI  - The multiple drug allergy syndrome: a matched-control retrospective study in
      patients allergic to penicillin.

PMID- 8757226
TI  - Occupational asthma caused by roasted coffee: immunologic evidence that roasted
      coffee contains the same antigens as green coffee, but at a lower concentration.

PMID- 8757227
TI  - Lipoprotein levels in elderly patients with asthma. Cardiovascular Health Study
      Research Group.

PMID- 8757228
TI  - Anaphylaxis caused by linseed (flaxseed) intake.

PMID- 8757229
TI  - Accupril- and Cozaar-induced angioedema in the same patient.

PMID- 8757230
TI  - Cockroach and Dermatophagoides pteronyssinus cross-react.

PMID- 8757231
TI  - Cross-sensitization between latex and fruits.

PMID- 8757232
TI  - Meta-analysis of leukemia and farming.
AB  - A series of meta-analyses of peer-reviewed studies of leukemia and farming were
      performed and examined in the context of what is currently known about risk
      factors for leukemia. The analyses yielded inconsistent results; however, the
      preponderance of positive studies and lack of apparent publication bias suggests
      a weak association between farming and the disease. Reported excesses of all
      major subtypes of leukemia in farmers suggest that the association between
      farming and disease is due to a variety of exposures, which result in an overall
      excess of leukemia. Reported associations with specific subtypes of the disease
      are based on low numbers of cases and inconsistent due to the lack of exposures
      to strong risk factors universally experienced by farmers.

PMID- 8757233
TI  - Erythrocyte protoporphyrin versus blood lead: relationship with iron status among
      children exposed to gross environmental pollution.
AB  - The dose-response relationship between erythrocyte protoporphyrin (EP) and blood
      lead (PbB) was investigated among children with different subgroups of iron
      status. The data bank from Santo Amaro City, Brazil, was taken to study 490
      children aged 1-9 years who lived at less than 900 m from a primary lead smelter.
      Mean PbB was 58.9 +/- 25.3 micrograms/dl and mean EP was 87.1 +/- 68.1
      micrograms/dl. At PbB levels lower than 60 micrograms/dl, the dose-response curve
      for EP versus PbB followed the classical pattern; children with low iron status
      showing greater EP "response" than those with typical iron status and those with
      high iron status, after controlling for the effects of age and racial group.
      Among children with PbB > or = 60 micrograms/dl, EP response increased according
      to the following order: typical < low < high iron status.

PMID- 8757235
TI  - The effects of sulfur dioxide inhalation and antioxidant vitamins on red blood
      cell lipoperoxidation.
AB  - An attempt was made to determine whether sulfur dioxide (SO2,) inhalation at 10
      ppm, 1 hr daily, for 30 days induces oxidant stress and whether vitamin E (40
      mg/kg) together with vitamin C (200 mg/kg), administered intraperitoneally once
      in every 3 days, can reduce the damage in red blood cell membranes of guinea
      pigs. Malonyldialdehyde (MDA) levels, osmotic fragility ratios, and methemoglobin
      and sulfhemoglobin values were significantly higher in the SO2-treated group
      compared with the control group (P < 0.05), and marked decreases in MDA levels
      and osmotic fragility ratios were determined in the group treated with SO2 +
      antioxidant vitamins (P < 0.05).

PMID- 8757234
TI  - Acute pulmonary toxicity of copper gallium diselenide, copper indium diselenide,
      and cadmium telluride intratracheally instilled into rats.
AB  - Acute toxicity studies were conducted on copper gallium diselenide (CGS), copper
      indium diselenide (CIS), and cadmium telluride (CT), three novel compounds used
      in the photovoltaic and semiconductor industries. Female Sprague-Dawley rats (six
      rats/dose) were administered 0, 12, 25, 50, or 100 mg/kg body wt of CGS, CIS, or
      CT by intratracheal instillation. At 72 hr after treatment, body weight gain was
      significantly decreased in the 100 mg/kg CIS group and in all CT dose groups.
      Lung weights were increased in most chemical-treated rats, with CT causing the
      greatest increase. Total numbers of cells in bronchoalveolar lavage fluid (BALF)
      were significantly increased in treated rats and were greatest in the 100 mg/kg
      CIS group. Differential cell counts of BALF demonstrated a marked decrease in the
      percentage of alveolar macrophages and an increase in the percentage of
      polymorphonuclear leukocytes in all dose groups of all three chemicals. Slight to
      moderate increases in lactate dehydrogenase activity were observed in BALF from
      CGS- and CIS-treated rats; marked increases were observed in CT-treated rats.
      BALF protein was significantly increased in rats treated with CIS and CT.
      Microscopic examination revealed lymphoid hyperplasia in lungs of rats treated
      with all three chemicals. CT caused necrosis of the terminal bronchiolar
      epithelium and epithelium of the alveolar duct region with inflammation,
      prominent fibrin exudates, and type II cell hyperplasia. CGS and CIS also caused
      intraalveolar inflammation and type II cell hyperplasia, but did not cause the
      necrosis and fibrin exudate observed in lungs of CT-treated rats. Based on
      changes in lung weight, BALF indices, and histopathology, CT was the most toxic
      for the lung; CIS had intermediate toxicity and CGS was the least toxic. The
      solubilities of CGS and CIS were relatively low and similar at both pH levels and
      do not readily explain the observed differences in pulmonary toxicity. The
      solubility of CdTe was considerably greater than that of CGS and CIS and likely
      contributed to the greater toxicity of this compound.

PMID- 8757236
TI  - Relation of a seafood diet to mercury, selenium, arsenic, and polychlorinated
      biphenyl and other organochlorine concentrations in human milk.
AB  - Human transition milk was sampled from 88 mothers at the Faroe Islands, where the
      seafood diet includes pilot whale meat and blubber. Milk mercury concentrations
      (median, 2.45 micrograms/liter) were significantly associated with mercury
      concentrations in cord blood and with the frequency of pilot whale dinners during
      pregnancy. Milk selenium concentrations (mean, 19.1 micrograms/liter) correlated
      significantly with concentrations in cord blood but not with seafood consumption.
      Arsenic concentrations were very low. Twenty-four of the milk samples were
      separated into four pools based on fish intake and milk mercury concentrations.
      The polychlorinated biphenyl (PCB) concentrations (1.8-3.5 micrograms/g lipid)
      were high and mainly due to congener numbers 153, 180, and 138. One pool
      contained a congener 77 concentration of 1380 ppt, which is the highest ever
      reported in a human specimen for a coplanar PCB. The highest PCB concentrations
      were seen in the pools from women who had eaten frequent whale dinners and whose
      milk contained high mercury concentrations. The concentrations of chlorinated
      dibenzo-p-dioxins and furans were not similarly elevated. Given the advantages
      associated with breast-feeding, advice to nursing mothers in this population
      should take into regard the possible risks associated with long-term exposure to
      milk contaminants.

PMID- 8757237
TI  - Removing the smoking confounder from blood volatile organic compounds
      measurements.
AB  - Because smoking is a major contributor to the internal dose levels of many
      volatile organic compounds (VOCs), it is difficult to assess other VOC exposures
      among smokers. Purge and trap/gas chromatography/isotope-dilution mass
      spectrometry was used to determine the internal dose of VOCs of smokers and
      nonsmokers. Median whole blood concentrations of benzene, styrene, and toluene
      were shown to be approximately two times higher among smokers than among
      nonsmokers. In addition, smoking elevated the blood levels of ethylbenzene, m-/p
      xylene, and o-xylene when the log-transformed data were compared. Smoking also
      led to greatly increased levels of 2,5-dimethylfuran. These results indicate that
      blood levels of many VOCs are highly correlated with blood levels of 2,5
      dimethylfuran and that this effect is primarily a result of smoking. The smoking
      confounder to blood levels of VOCs can be removed by including the concentration
      of blood 2,5-dimethylfuran concentration when evaluating results from a health
      and exposure evaluation. Determining the blood 2,5-dimethylfuran concentration
      appears to be an effective means of correcting the confounding influence of
      smoking and supplies a way of determining lower-level exposures that previously
      could not have been distinguished from the effects of smoking.

PMID- 8757238
TI  - Dietary intake of cadmium and lead among the general population in Korea.
AB  - This survey was conducted in Seoul, Pusan, Chunan, and Haman in Korea to clarify
      cadmium and lead burden in the general Korean populations in terms of dietary
      intake of cadmium and lead and the concentrations of the two metals in blood.
      People who participated in the study were 141 healthy nonsmoking women aged 21-56
      years. Determination of cadmium and lead in 24-hr food duplicates and blood
      samples was carried out by graphite furnace atomic absorption spectrophotometry.
      The geometric means for the four sites in combination were 21.2 micrograms/day
      for dietary cadmium, 20.5 micrograms/day for dietary lead, 1.27 ng/ml for blood
      cadmium, and 44.3 ng/ml for blood lead. Cadmium intake from boiled rice accounted
      for 23% of total daily cadmium intake. The counterpart value for lead intake from
      boiled rice was 12%. Blood cadmium levels and dietary cadmium intake were lower
      and blood lead level and dietary lead intake were higher in Korean women than in
      Japanese women. The values for dietary cadmium are similar to, and the values for
      dietary lead are somewhat lower than, the levels reported from Europe and the
      United States. Dietary intake was the main source of cadmium exposure, whereas
      lead exposure was from both ambient air and foods in the Korean population.

PMID- 8757239
TI  - Survey of New Jersey schools and day care centers for lead in plumbing solder.
      Identification of lead solder and prevention of exposure to drinking water
      contaminated with lead from plumbing solder.
AB  - Levels of lead in drinking water can be high enough to pose a potential health
      threat to very young children, primarily from the use of lead solder for indoor
      plumbing. In February 1987, New Jersey banned lead solder for use in the
      installation or repair of drinking water plumbing systems. However, because lead
      solder continued to be available for purchase in the state, New Jersey Department
      of Health staff sought to (i) determine the extent to which schools and day care
      centers were in compliance with the ban, and (ii) determine the effectiveness of
      a solder analysis test kit commonly used by plumbing inspectors in the field.
      Samples of solder were collected from 53 day care centers and 37 schools known to
      have been constructed or renovated after the ban took effect. Samples from 24% of
      those facilities constructed or renovated just after the lead ban (1987-1988)
      tested positive for lead content. However, for those facilities constructed or
      renovated in later years (1989-1992), there was a decline in the percentage of
      samples that tested positive for lead content. For this period of time, 13% of
      the samples tested positive for lead. In total, more than 10% of facilities with
      new plumbing installed between 1987 and 1992 had solder samples that tested
      positive for lead. A lead in solder test kit commonly used by inspectors proved
      to be an effective screening tool for the field. The New Jersey Department of
      Health recommends continued enforcement of the lead solder ban through inspection
      and encouragement of behaviors that minimize consumption of potentially lead
      contaminated drinking water. In order to assess patterns of water use, staff at
      the day care centers were asked to complete a questionnaire. Sixty-seven percent
      of the respondents reported that they "always" use water from the cold tap when
      preparing drinks or food for the children. In addition, 57% reported that they
      always first flush the tap before using the water for drinking or food purposes.
      Posters and pamphlets developed by the department and containing recommendations
      for how to minimize consumption of lead-contaminated drinking water were also
      provided.

PMID- 8757240
TI  - DNA strand breakage, thymine glycol production, and hydroxyl radical generation
      induced by different samples of crystalline silica in vitro.
AB  - Five preparations of alpha-quartz [Min-U-Sil 5 (MQZ), MQZ pretreated with
      hydrofluoric acid (HFMQZ), Chinese standard alpha-quartz (CSQZ), and two German
      samples, DQ-12 and F600] and two preparations of the crystalline silica
      polymorphs, cristobalite and tridymite, previously characterized for surface area
      and surface charge, were evaluated for their relative activities in the following
      assays: (i) in vitro assays of short duration (< or = 15 min) for oxygen
      consumption and for generation of hydroxyl radicals (measured by electron spin
      resonance spin trapping), and (ii) in vitro assays of longer duration for DNA
      strand breakage (measured using linear DNA as a detector molecule) and for
      production of the oxidized DNA base, thymine glycol (measured by gas
      chromatography-mass spectrometry). Marked differences among the samples were
      found for their levels of oxygen consumption and of hydroxyl radicals'
      generation. All samples caused increased formation of thymine glycol, with wide
      variations in activity among samples. When normalized for equal surface area, the
      samples produced different levels of DNA strand breakage. Addition of hydrogen
      peroxide strongly accelerated DNA damage--more for cristobalite than for the
      alpha-quartz samples. DNA damage by quartz was enhanced by ferric chloride and
      inhibited by iron chelators. The order of relative activity of the samples varied
      with different types of in vitro assays and was not directly correlated to
      surface area. Electrophoretic mobility, as measured by zeta potential, was not
      significantly different among samples. The results suggest that the ability of
      different crystalline silica samples to generate a rapid burst of oxygen free
      radicals is distinct from their ability to induce DNA damage and DNA base
      oxidation over longer time periods. The relative activities of the samples in
      cellular assays (hemolysis of human erythrocytes; cytotoxicity and neoplastic
      transformation of BALB/3T3/A31-1-1 cells) were in turn markedly different from
      those listed above, suggesting a more critical role for surface area. The
      mechanisms of carcinogenesis by crystalline silica need to be further
      investigated in relation to the underlying physicochemical characteristics.

PMID- 8757241
TI  - Gonadotropin-releasing hormone and NMDA receptor gene expression and
      colocalization change during puberty in female rats.
AB  - During development, an increase in gonadotropin-releasing hormone (GnRH) release
      occurs that is critical for the initiation of puberty. This increase is
      attributable, at least in part, to activation of the GnRH neurosecretory system
      by inputs from neurotransmitters, such as glutamate, acting via NMDA receptors.
      We examined changes in GnRH and NMDA-R1 gene expression by RNase protection assay
      of preoptic area-anterior hypothalamic (POA-AH) dissections of female rats
      undergoing normal puberty or in which precocious puberty was induced by treatment
      with the glutamate agonist NMA. GnRH mRNA levels increased significantly
      throughout normal development; this was accelerated by treatment with NMA. NMDA
      R1 mRNA levels increased only between P10 and P20. The acceleration of the
      elevation in GnRH mRNA levels by NMDA suggests that a stimulation of GnRH gene
      expression may be a rate-limiting factor for the onset of puberty. This is
      attributable to a post-transcriptional mechanism because GnRH primary transcript
      levels, an index of proGnRH gene transcription, were not observed to change
      during puberty. Alterations in the colocalization of GnRH neurons with the NMDA
      R1 subunit during puberty also were assessed immunocytochemically. The percentage
      of GnRH neurons that double-labeled with NMDA-R1 was 2% in prepubertal rats and
      3% in pubertal rats; this increased to 19% in postpubertal rats. Taken together,
      these studies suggest that an increase in glutamatergic input to GnRH neurons
      plays a role in the increase in GnRH release and gene expression that occurs at
      the initiation of puberty.

PMID- 8757242
TI  - Morphology and physiology of cortical neurons in layer I.
AB  - The electrophysiological and morphological properties of layer I neurons were
      studied in visual cortex slices from 7- to 19-d-old rats using whole-cell
      recording and biocytin labeling. A heterogeneous population of small,
      nonpyramidal neurons was found. Approximately one third of the cells we recorded
      were neurogliaform cells; another third were multipolar neurons with axons
      descending out of layer I. The remaining cells were heterogeneous and were not
      classified. In slices from 7- to 10-d-old animals only, we identified Cajal
      Retzius cells. Neurogliaform neurons had a very dense local axonal field, which
      was largely contained within layer I. Cells with descending axons had a
      relatively sparse local axonal arbor and projected at least to layer II and
      sometimes deeper. Spiking in neurogliaform neurons was followed by an
      afterdepolarizing potential, whereas spiking in cells with descending axons was
      followed by a slow after-hyperpolarizing potential (AHP). In addition,
      neurogliaform cells exhibited less spike broadening and a larger fast AHP after
      single spikes than did cells with descending axons. Generally, cells in layer I
      received synaptic inputs characterized as either GABA- or glutamate-mediated,
      suggesting the presence of excitatory and inhibitory inputs. With their output
      largely limited to layer I, neurogliaform cells could synapse with other layer I
      neurons, the most distal dendritic branches of pyramidal cells, or the dendrites
      of layer II/III interneurons, which invade layer I. Cells with descending axons
      could contact a wide variety of cortical cells throughout their vertical
      projection.

PMID- 8757243
TI  - Laminar localization, morphology, and physiological properties of pyramidal
      neurons that have the low-threshold calcium current in the guinea-pig medial
      frontal cortex.
AB  - One of the several types of ionic currents present in central neurons is the low
      threshold, or T-type calcium current (LTCC). This current is responsible for the
      firing of low-threshold calcium spikes (LTS) and participates in the generation
      of rhythmic activity and bursts of action potentials in several brain nuclei. We
      have studied the distribution and properties of pyramidal neurons recorded from
      the guinea-pig medial frontal cortex that have this calcium current. Pyramidal
      neurons were recorded in an in vitro slice preparation using either current clamp
      or single-electrode voltage-clamp recording. Pyramidal neurons that generated LTS
      or had the LTCC were found only between 500 mm from the pial surface and the
      white matter (approximately layers V/VI) and were absent in more superficial
      layers. All pyramidal neurons that fired LTS or had the LTCC were characterized
      as regular spiking and had some important morphological and physiological
      differences from the rest of the pyramidal neurons studied. This group of neurons
      had shorter and less complex apical dendritic arbors, fired action potentials of
      lower amplitude and longer duration, and were the only type of pyramidal neurons
      able to generate bursts of action potentials. In addition, the inhibitory
      synaptic potentials elicited by stimulation of layer I were more powerful in this
      group of neurons. This research provides new evidence for the presence of the
      LTCC in subsets of cortical pyramidal neurons, which have specific and well
      defined morphological and physiological properties.

PMID- 8757244
TI  - Calcium-dependent paired-pulse facilitation of miniature EPSC frequency
      accompanies depression of EPSCs at hippocampal synapses in culture.
AB  - Two forms of evoked neurotransmitter release at excitatory synapses between
      cultured hippocampal neurons have been described. After an action potential, it
      has been shown that transmitter initially is released synchronously, and this is
      followed by a period of "slow" asynchronous release. The "fast" synchronous
      component of release at these synapses has been found routinely to demonstrate
      paired-pulse and tetanic depression, whereas the short-term plasticity of
      asynchronous release has not been investigated. In the present experiments, we
      have used the whole-cell patch-clamp technique to record from pairs of neurons in
      a low-density hippocampal culture preparation to determine both the properties
      and underlying mechanisms of short-term plasticity of asynchronous release. It
      was found that an increase in miniature EPSC (mEPSC) frequency accompanied both
      single and multiple stimuli, and this mEPSC increase was facilitated during
      paired stimuli, even when the evoked synchronous release was depressed. In
      addition, both the activity-dependent depression of evoked EPSCs and facilitation
      of asynchronous mEPSC release were dependent on Ca accumulation in the nerve
      terminal. However, the Ca-dependent mechanisms underlying these two processes
      could be distinguished by the differential effects of two membrane-permeant
      calcium chelators, BAPTA-AM and EGTA-AM. Frequency-dependent depression of evoked
      EPSCs involves a rapid rise in intraterminal Ca, which likely triggers a process
      that proceeds in a Ca-independent manner, whereas the asynchronous release may be
      linked more directly to a sustained increase in intraterminal Ca.

PMID- 8757245
TI  - Bidirectional regulation of protein kinase M zeta in the maintenance of long-term
      potentiation and long-term depression.
AB  - Long-term potentiation (LTP) and long-term depression (LTD) are persistent
      modifications of synaptic efficacy that may contribute to information storage in
      the CA1 region of the hippocampus. Persistently enhanced phosphorylation has been
      implicated in the maintenance phase of LTP. This hypothesis is supported by our
      previous observation that protein kinase M zeta (PKM zeta), the constitutively
      active catalytic fragment of a single protein kinase C isoform (PKC zeta),
      increases in LTP maintenance. In contrast, dephosphorylation may be important in
      LTD maintenance, because phosphatase inhibitors reverse established LTD, in
      addition to blocking its induction. Because phosphorylation is determined by a
      balance of phosphatases and kinases, both increases in phosphatase activity and
      decreases in kinase activity could contribute to LTD. We now report that the
      reduction of protein kinase activity by H7, as well as selective inhibition of
      PKC by chelerythrine, mimics and occludes the maintenance phase of homosynaptic
      LTD in rat hippocampal slices. Conversely, saturated LTD occludes the synaptic
      depression caused by chelerythrine. Biochemical analysis demonstrates a decrease
      of PKM zeta, as well as PKCs gamma and epsilon, in LTD maintenance and a
      concomitant loss of constitutive PKC activity. LTD and the downregulation of PKM
      zeta are prevented by NMDA receptor antagonists and Ca(2+)-dependent protease
      inhibitors. Both LTD and the downregulation of PKM zeta are reversible by high
      frequency afferent stimulation. Our findings indicate that the molecular
      mechanisms of LTP and LTD maintenance are inversely related through the
      bidirectional regulation of PKC.

PMID- 8757246
TI  - Long-term potentiation in distinct subtypes of hippocampal nonpyramidal neurons.
AB  - We have investigated NMDA receptor-dependent long-term potentiation (LTP) in
      distinct subtypes of nonpyramidal neurons of the CA1 hippocampus using induction
      protocols that permitted the differentiation between a direct form of LTP and
      plasticity resulting simply from the "passive propagation" of LTP occurring on
      CA1 pyramidal neurons. Two types of stratum (st.) oriens/ alveus interneurons
      received passive propagation of synaptic potentiation via the recurrent
      collaterals of CA1 pyramidal cells, but neither subtype possessed direct
      plasticity. In st. radiatum, two distinct classes of cells were observed: st.
      radiatum interneurons that showed neither direct nor propagated forms of synaptic
      plasticity, and "giant cells" for which EPSPs were robustly potentiated after a
      pairing protocol. This potentiation is similar to the LTP described in pyramidal
      cells, and its induction requires NMDA receptor activation. Thus, a large
      heterogeneity of synaptic plasticity exists in morphologically distinct neurons
      and suggests that complex changes in the CA1 network properties will occur after
      the induction of LTP.

PMID- 8757247
TI  - A distinct pattern of trophic factor expression in myelin-deficient nerves of
      Trembler mice: implications for trophic support by Schwann cells.
AB  - Distal to a peripheral nerve transection, myelin degradation and Schwann cell
      (SC) proliferation are accompanied by a marked upregulation of brain-derived
      neurotrophic factor (BDNF) and a decrease of ciliary neurotrophic factor (CNTF)
      in non-neuronal cells. To investigate the role of SC differentiation in trophic
      factor regulation, we studied BDNF and CNTF expression in sciatic nerves from
      Trembler-J (Tr-J) mice. In these animals, a mutation in the pmp-22 gene causes a
      failure of myelination and continuous SC proliferation, but axonal continuity is
      preserved. In spite of the severe abnormalities in Tr-J nerves, BDNF levels
      remained as low as in the intact controls. Thus, the primary SC disorder in Tr-J
      produces a different pattern of BDNF expression from that caused by axonal
      breakdown due to nerve transection. Furthermore, the upregulation of BDNF mRNA
      triggered by transection was 70-fold in control nerves, but only 30-fold in Tr-J
      sciatic nerves. Because these results raised the possibility that axonal loss may
      influence neurotrophin expression only in SCs that have differentiated toward a
      myelinating phenotype, we measured BDNF mRNA after axotomy in the cervical
      sympathetic trunk (CST), a predominantly unmyelinated autonomic nerve. In
      contrast to the sciatic nerves, the BDNF mRNA level barely increased in the
      injured CST, supporting the idea that not all SCs are equal sources of trophic
      molecules. In Tr-J sciatic nerves, CNTF mRNA levels were fourfold lower than
      normal, implying that the downregulation of this cytokine is a sensitive
      indicator of a spectrum of SC perturbations that affect myelinating cells.

PMID- 8757248
TI  - Impaired differentiation of Schwann cells in transgenic mice with increased PMP22
      gene dosage.
AB  - An intrachromosomal duplication containing the PMP22 gene is associated with the
      human hereditary peripheral neuropathy Charcot-Marie-Tooth disease type 1A, and
      PMP22 overexpression as a consequence of increased PMP22 gene dosage has been
      suggested as causative event in this frequent disorder of peripheral nerves. We
      have generated transgenic mice that carry additional copies of the pmp22 gene to
      prove that increased PMP22 gene dosage is sufficient to cause PNS myelin
      deficiencies. Mice carrying approximately 16 and 30 copies of the pmp22 gene
      display a severe congenital hypomyelinating neuropathy as characterized by an
      almost complete lack of myelin and marked slowing of nerve conductions. Affected
      nerves contain an increased number of nonmyelinating Schwann cells, which do not
      form onion bulbs but align in association with axons. The mutant Schwann cells
      are characterized by a premyelination-like state as indicated by the expression
      of embryonic Schwann cell markers. Furthermore, continued Schwann cell
      proliferation is observed into adulthood. We hypothesize that Schwann cells are
      impaired in their differentiation into the myelinating phenotype, leading to a
      disorder comparable to severe cases of hereditary motor and sensory neuropathies.
      Our findings, combined with the analysis of heterozygous and homozygous PMP22
      deficient mice, indicate that aberrant pmp22 gene copy numbers cause various
      forms of myelination defects.

PMID- 8757249
TI  - Mice lacking brain-derived neurotrophic factor exhibit visceral sensory neuron
      losses distinct from mice lacking NT4 and display a severe developmental deficit
      in control of breathing.
AB  - The neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5
      (NT4) act via the TrkB receptor and support survival of primary somatic and
      visceral sensory neurons. The major visceral sensory population, the nodose
      petrosal ganglion complex (NPG), requires BDNF and NT4 for survival of a full
      complement of neurons, providing a unique opportunity to compare gene dosage
      effects between the two TrkB ligands and to explore the possibility that one
      ligand can compensate for loss of the other. Analysis of newborn transgenic mice
      lacking BDNF or NT4, or BDNF and NT4, revealed that survival of many NPG
      afferents is proportional to the number of functional BDNF alleles, whereas only
      one functional NT4 allele is required to support survival of all NT4-dependent
      neurons. In addition, subpopulation analysis revealed that BDNF and NT4 can
      compensate for the loss of the other to support a subset of dopaminergic ganglion
      cells. Together, these data demonstrate that the pattern of neuronal dependencies
      on BDNF and NT4 in vivo is far more heterogeneous than predicted from previous
      studies in culture. Moreover, BDNF knockout animals lack a subset of afferents
      involved in ventilatory control and exhibit severe respiratory abnormalities
      characterized by depressed and irregular breathing and reduced chemosensory
      drive. BDNF is therefore required for expression of normal respiratory behavior
      in newborn animals.

PMID- 8757250
TI  - Extracellular synthesis of cADP-ribose from nicotinamide-adenine dinucleotide by
      rat cortical astrocytes in culture.
AB  - cADPR is an endogenous calcium-mobilizing agent that in vertebrates is
      synthesized from nicotinamide-adenine dinucleotide (NAD) by bifunctional enzymes
      with ADP-ribosyl cyclase and cADPR hydrolase activity. ADP-ribosyl cyclase and
      cADPR hydrolase activity have been reported in the brain, but the cellular
      localization of these activities has not been determined previously. In the
      present study, selective culturing techniques were employed to localize ADP
      ribosyl cyclase activity and cADPR hydrolase activity to astrocytes or neurons in
      cultures derived from rat embryonic cerebral cortex. ADP-ribosyl cyclase activity
      was determined by incubating cultures with 1 mM NAD in the extracellular medium
      for 60 min at 37 degrees C and measuring formation of cADPR by bioassay and by
      HPLC. Astrocyte cultures and mixed cultures of astrocytes and neurons had mean
      specific activities of 0.84 +/- 0.06 and 0.9 +/- 0.18 nmol cADPR produced/mg
      protein/hr, respectively. No detectable ADP-ribosyl cyclase activity was found in
      neuron-enriched/ astrocyte-poor cultures. cADPR hydrolase activity was detectable
      by incubating cultures with 300 microM cADPR for 60 min at 37 degrees C and
      assaying loss of cADPR or accumulation of ADPR. The demonstration of
      extracellular ADP-ribosyl cyclase and cADPR hydrolase activities associated with
      astrocytes may have important implications for the role of extracellular cADPR in
      signal transduction and in intercellular communication in the nervous system.

PMID- 8757251
TI  - Increased susceptibility to induction of long-term depression and long-term
      potentiation reversal during aging.
AB  - Homosynaptic long-term depression (LTD) and reversal of long-term potentiation
      (LTP) were examined extracellularly at CA3-CA1 synapses in stratum radiatum of
      slices from adult (6-9 months) and aged (20-24 months) Fischer 344 rats.
      Prolonged low-frequency stimulation (LFS) (900 pulses/1 Hz) of the Schaffer
      collaterals depressed the initial slope of the excitatory postsynaptic potential
      (EPSP) in aged but not adult rats. LTD at aged synapses was pathway-specific,
      persistent, and sensitive to the NMDA receptor antagonist DL-2-amino-5
      phosphonopentanoic acid (AP5). Adult slices exhibited AP5-sensitive LTD in high
      [Ca2+] medium, whereas LTD in aged slices was blocked by high [Mg2+], suggesting
      that differences in Ca2+ regulation may underlie susceptibility to LTD. Despite
      age-related differences in LTD induction, no age difference in LTP magnitude was
      revealed. Additionally, LFS delivered 60 min after LTP induction resulted in
      similar LTP reversal for both age groups. Susceptibility differences to LTP
      reversal were indicated after multiple short-duration LFS bursts (30 pulses/1
      Hz), with each burst separated by 10 min. Aged synapses exhibited significant
      reversal after a single burst and complete reversal after three LFS episodes. In
      adult slices, LTP reversal appeared after the fourth burst, and at no time was
      LTP depressed to initial baseline levels. This study provides the first
      characterization of homosynaptic LTD/LTP reversal in the aged animal and
      demonstrates that one form of plasticity, depression attributable to LFS, is
      increased during aging.

PMID- 8757252
TI  - Mechanisms of H+ and Na+ changes induced by glutamate, kainate, and D-aspartate
      in rat hippocampal astrocytes.
AB  - The excitatory transmitter glutamate (Glu), and its analogs kainate (KA), and D
      aspartate (D-Asp) produce significant pH changes in glial cells. Transmitter
      induced pH changes in glial cells, generating changes in extracellular pH, may
      represent a special form of neuronal-glial interaction. We investigated the
      mechanisms underlying these changes in intracellular H+ concentration ([H+]i) in
      cultured rat hippocampal astrocytes and studied their correlation with increases
      in intracellular Na+ concentration ([Na+]i), using fluorescence ratio imaging
      with 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) or sodium-binding
      benzofuran isophthalate (SBFI). Glu, KA, or D-Asp evoked increases in [Na+]i; Glu
      or D-Asp produced parallel acidifications. KA, in contrast, evoked biphasic
      changes in [H+]i, alkaline followed by acid shifts, which were unaltered after
      Ca2+ removal and persisted in 0 CI(-)-saline, but were greatly reduced in
      CO2/HCO3(-)-free or Na(+)-free saline, or during 4,4'-diisothiocyanato-stilbene
      2,2'-disulphonic acid (DIDS) application. The non-NMDA receptor antagonist 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocked KA-evoked changes in [H+]i and
      [Na+]i, indicating that they were receptor-ionophore mediated. In contrast, CNQX
      increased the [H+]i change and decreased the [Na+]i change induced by Glu. D-Asp,
      which is transported but does not act at Glu receptors, induced [H+]i and [Na+]i
      changes that were virtually unaltered by CNQX. Our study indicates that [Na+]i
      increases are not primarily responsible for Glu- or KA-induced acidifications in
      astrocytes. Instead, intracellular acidifications evoked by Glu or D-Asp are
      mainly caused by transmembrane movement of acid equivalents associated with
      Glu/Asp-uptake into astrocytes. KA-evoked biphasic [H+]i changes, in contrast,
      are probably attributable to transmembrane ion movements mediated by inward,
      followed by outward, electrogenic Na+/HCO3- cotransport, reflecting KA-induced
      biphasic membrane potential changes.

PMID- 8757253
TI  - Ion binding and permeation at the GABA transporter GAT1.
AB  - This study addresses the binding of ions and the permeation of substrates during
      function of the GABA transporter GAT1. GAT1 was expressed in Xenopus oocytes and
      studied electrophysiologically as well as with [3H]GABA flux; GAT1 was also
      expressed in mammalian cells and studied with [3H]GABA and [3H]tiagabine binding.
      Voltage jumps, Na+ and Cl- concentration jumps, and exposure to high-affinity
      blockers (NO-05-711 and SKF-100330A) all produce capacitive charge movements.
      Occlusive interactions among these three types of perturbations show that they
      all measure the same population of charges. The concentration dependences of the
      charge movements reveal (1) that two Na+ ions interact with the transporter even
      in the absence of GABA, and (2) that Cl- facilitates the binding of Na+.
      Comparison between the charge movements and the transport-associated current
      shows that this initial Na(+)-transporter interaction limits the overall
      transport rate when [GABA] is saturating. However, two classes of manipulation-
      treatment with high-affinity uptake blockers and the W68L mutation-"lock" Na+
      onto the transporter by slowing or preventing the subsequent events that release
      the substrates to the intracellular medium. The Na+ substitutes Li+ and Cs+ do
      not support charge movements, but they can permeate the transporter in an
      uncoupled manner. Our results (1) support the hypothesis that efficient removal
      of synaptic transmitter by the GABA transporter GAT1 depends on the previous
      binding of Na+ and Cl-, and (2) indicate the important role of the conserved
      putative transmembrane domain 1 in interactions with the permeant substrates.

PMID- 8757254
TI  - Stoichiometry of a recombinant GABAA receptor.
AB  - GABA is the main inhibitory neurotransmitter in the mammalian brain. The
      postsynaptic GABAA receptor/pore complex is presumed to be a pentamer typically
      composed of a combination of alpha, beta, and gamma subunits, although the
      stoichiometry remains controversial. We probed the stoichiometry of the GABAA
      receptor by site-directed mutagenesis of a conserved leucine (to serine) in the
      putative second membrane-spanning domain of the rat alpha 1(alpha L263S), beta
      2(alpha L259S), and gamma 2(alpha L274S) subunit isoforms. Coexpression of wild
      type and mutant subunits of each class (e.g., alpha and alpha L263S), along with
      their wild-type counter-parts (e.g., beta and gamma), in Xenopus laevis oocytes
      resulted in mixed populations of receptors with distinct GABA sensitivities. This
      is consistent with the interpretation that the leucine mutation increased the
      GABA sensitivity in proportion to the number of incorporated mutant subunits. The
      apparent number of incorporated subunits for each class (alpha, beta, and gamma)
      could then be determined from the number of components comprising the compound
      GABA dose-response relationships. Using this approach, we conclude that the
      recombinant alpha 1 beta 2 gamma 2 GABAA receptor is a pentamer composed of two
      alpha subunits, two beta subunits, and one gamma subunit.

PMID- 8757256
TI  - Systemic administration of a nerve growth factor conjugate reverses age-related
      cognitive dysfunction and prevents cholinergic neuron atrophy.
AB  - Intraventricular administration of nerve growth factor (NGF) in rats has been
      shown to reduce age-related atrophy of central cholinergic neurons and the
      accompanying memory impairment. Intraventricular administration of NGF is
      necessary because NGF will not cross the blood-brain barrier (BBB). Here we have
      used a novel carrier system, consisting of NGF covalently linked to an anti
      transferrin receptor antibody (OX-26), to transport biologically active NGF
      across the BBB. In our experiment, aged (24 months old) Fischer 344 rats received
      intravenous injections of the OX-26-NGF conjugate or a control solution (a
      mixture of unconjugated OX-26 and NGF) twice weekly for 6 weeks. The OX-26-NGF
      injections resulted in a significant improvement in spatial learning in
      previously impaired rats but disrupted the learning ability of previously
      unimpaired rats. Neuroanatomical analyses showed that OX-26-NGF conjugate
      treatment resulted in a significant increase in cholinergic cell size in the
      medial septal region of rats initially impaired in spatial learning. These
      results indicate the potential use of the transferrin receptor antibody delivery
      system for treatment of CNS disorders with neurotrophic proteins.

PMID- 8757255
TI  - Calcium influx via the NMDA receptor induces immediate early gene transcription
      by a MAP kinase/ERK-dependent mechanism.
AB  - The regulation of gene expression by neurotransmitters is likely to play a key
      role in neuroplasticity both during development and in the adult animal.
      Therefore, it is important to determine the mechanisms of neuronal gene
      regulation to understand fully the mechanisms of learning, memory, and other long
      term adaptive changes in neurons. The neurotransmitter glutamate stimulates rapid
      and transient induction of many genes, including the c-fos proto-oncogene. The c
      fos promoter contains several critical regulatory elements, including the serum
      response element (SRE), that mediate glutamate-induced transcription in neurons;
      however, the mechanism by which the SRE functions in neurons has not been
      defined. In this study, we sought to identify transcription factors that mediate
      glutamate induction of transcription through the SRE in cortical neurons and to
      elucidate the mechanism(s) of transcriptional activation by these factors. To
      facilitate this analysis, we developed an improved calcium phosphate
      coprecipitation procedure to transiently introduce DNA into primary neurons, both
      efficiently and consistently. Using this protocol, we demonstrate that the
      transcription factors serum response factor (SRF) and Elk-1 can mediate glutamate
      induction of transcription through the SRE in cortical neurons. There are at
      least two distinct pathways by which glutamate signals through the SRE: an SRF
      dependent pathway that can operate in the absence of Elk and an Elk-dependent
      pathway. Activation of the Elk-dependent pathway of transcription seems to
      require phosphorylation of Elk-1 by extracellular signal-regulated kinases
      (ERKs), providing evidence for a physiological function of ERKs in glutamate
      signaling in neurons. Taken together, these findings suggest that SRF, Elk, and
      ERKs may have important roles in neuroplasticity.

PMID- 8757257
TI  - Traffic of dynamin within individual Drosophila synaptic boutons relative to
      compartment-specific markers.
AB  - Presynaptic terminals contain several specialized compartments, which have been
      described by electron microscopy. We show in an identified Drosophila
      neuromuscular synapse that several of these compartments-synaptic vesicle
      clusters, presynaptic plasma membrane, presynaptic cytosol, and axonal
      cytoskeleton-labeled by specific reagents may be resolved from one another by
      laser scanning confocal microscopy. Using a panel of compartment-specific markers
      and Drosophila shibire(ts1) mutants to trap an intermediate stage in synaptic
      vesicle recycling, we have examined the localization and redistribution of
      dynamin within single synaptic varicosities at the larval neuromuscular junction.
      Our results suggest that dynamin is not a freely diffusible molecule in resting
      nerve terminals; rather, it appears localized to synaptic sites by association
      with yet uncharacterized presynaptic components. In shi(ts1) nerve terminals
      depleted of synaptic vesicles, dynamin is quantitatively redistributed to the
      plasma membrane. It is not, however, distributed uniformly over presynaptic
      plasmalemma; instead, fluorescence images show "hot spots" of dynamin on the
      plasma membrane of vesicle-depleted nerve terminals. We suggest that these
      dynamin-rich domains may mark the active zones for synaptic vesicle endocytosis
      first described at the frog neuromuscular junction.

PMID- 8757258
TI  - Ca(2+)-permeable AMPA/kainate and NMDA channels: high rate of Ca2+ influx
      underlies potent induction of injury.
AB  - Neurodegeneration may occur secondary to glutamate-triggered Ca2+ influx through
      any of three routes: NMDA channels, voltage-sensitive Ca2+ channels (VSCC), and
      Ca(2+)-permeable AMPA/kainate channels (Ca-A/K). This study aims to examine Ca2+
      ion dynamics in the generation of excitotoxic injury by correlating the relative
      amounts of 45Ca2+ that flow into cortical neurons through each of these routes
      over a 10 min epoch ("10 min Ca2+ loads;" a measure of influx rate), with
      resultant levels of intracellular free Ca2+ ([Ca2+]) and subsequent injury.
      Neurons possessing Ca-A/K make up a small subset (approximately 13%) of cortical
      neurons in culture, which can be identified by a histochemical stain based on
      kainate-stimulated Co2+ uptake (Co2+ (+) neurons) and which are unusually
      vulnerable to AMPA/kainate receptor-mediated injury. Initial studies using brief
      kainate exposures (to selectively destroy Co2+ (+) neurons) along with kainate
      triggered 45Ca2+ influx measurements suggested that kainate causes rapid Ca2+
      influx into Co2+ (+) neurons (comparable to that caused by NMDA). Influx through
      both Ca-A/K and NMDA channels increased proportionately with extracellular Ca2+,
      suggesting that these channels have high Ca2+ permeability. When cultures were
      subjected to exposures that gave similar 10 min Ca2+ loads through different
      routes, comparable levels of injury were observed, suggesting that net
      intracellular Ca2+ accumulation is a critical determinant of injury. However, the
      relationship between [Ca2+]i and influx was less direct: although exposures that
      gave the lowest or highest 10 min Ca2+ loads showed correspondingly lower or
      higher mean [Ca2+]i responses, there appears to be a wide range of exposures over
      which individual neuronal differences and sequestration/buffering mechanisms
      obscure [Ca2+]i as a reflection of influx rate.

PMID- 8757259
TI  - Regenerative proliferation in organ cultures of the avian cochlea: identification
      of the initial progenitors and determination of the latency of the proliferative
      response.
AB  - Sensory hair cells in the cochleae of birds are regenerated after the death of
      preexisting hair cells caused by acoustic over-stimulation or administration of
      ototoxic drugs. Regeneration involves renewed proliferation of cells in an
      epithelium that is otherwise mitotically quiescent. To determine the identity of
      the first cells that proliferate in response to the death of hair cells and to
      measure the latency of this proliferative response, we have studied hair-cell
      regeneration in organ culture. Cochleae from hatchling chicks were placed in
      culture, and hair cells were killed individually by a laser microbeam. The
      culture medium was then replaced with a medium that contained a labeled DNA
      precursor. The treated cochleae were incubated in the labeling media for
      different time periods before being fixed and processed for the visualization of
      proliferating cells. The first cells to initiate DNA replication in response to
      the death of hair cells were supporting cells within the cochlear sensory
      epithelium. All of the labeled supporting cells were located within 200 microns
      of the hair-cell lesions. These cells first entered S-phase approximately 16 hr
      after the death of hair cells. The results indicate that supporting cells are the
      precursors of regenerated hair cells and suggest that regenerative proliferation
      of supporting cells is triggered by signals that act locally within the damaged
      epithelium.

PMID- 8757260
TI  - Astrocyte growth, reactivity, and the target of the antiproliferative antibody,
      TAPA.
AB  - Reactive astrocytes form a scar after injury to the CNS that many investigators
      believe contributes to the lack of functional regeneration. In the present study,
      we identify an astrocytic membrane protein that appears to play an important role
      in reactive gliosis and scar formation. Cultures of rat astrocytes were used as a
      model system to produce and to screen monoclonal antibodies that would alter cell
      growth. One antibody, AMP1, was identified that depresses the mitotic activity of
      cultured glial cells and alters their morphology. Expression cloning reveals that
      the antigen on the external surface of the cultured glial cells has a high degree
      of homology with the human lymphocyte protein called Target of the Anti
      Proliferative Antibody (TAPA-1; this rat protein will be referred to as rTAPA).
      rTAPA is a member of the tetramembrane-spanning superfamily of proteins and, as
      with other members of this family of proteins, rTAPA is associated with the
      regulation of cellular interactions and mitotic activity. After an injury to the
      cerebral cortex, there is a dramatic increase in AMP1 immunoreactivity that is
      spatially restricted to the reactive astrocytes at the glial scar. This change
      represents an upregulation of a membrane protein, rTAPA, that is approximately
      equal to the increase observed for glial fibrillary acidic protein. The high
      levels of rTAPA at the site of CNS injury and the AMP1 antibody perturbation
      studies indicate that rTAPA may play a prominent role in the response of
      astrocytes to injury and in glial scar formation.

PMID- 8757261
TI  - Spatially restricted increase in polysialic acid enhances corticospinal axon
      branching related to target recognition and innervation.
AB  - The polysialic acid (PSA) modification of the neural cell adhesion molecule
      (NCAM) has been shown to alter the responses of developing axons to their
      environment. We have studied the potential role of PSA in regulating the
      innervation of the spinal cord by corticospinal axons, which occurs by a delayed
      formation of collateral branches from the parent axons. Developmental changes in
      the distribution of PSA were examined immuno-histochemically using light and
      electron microscopy. Whereas NCAM is distributed along the entire pathway of rat
      corticospinal axons as they grow from the cortex to the spinal cord, PSA-modified
      NCAM does not become evident until later. When PSA becomes evident, it is
      restricted to the distal segment of these axons from the caudal hindbrain through
      the spinal cord. The increase in PSA on corticospinal axons coincides with the
      time that they begin to form collateral branches in the spinal cord. This unique
      spatiotemporal distribution of PSA suggests its involvement in corticospinal axon
      branching. To test this hypothesis, PSA was selectively removed by an in vivo
      injection of endoneuraminidase N. This treatment did not seem to interfere with
      the pathfinding of corticospinal axons; however, PSA removal delayed the onset of
      collateral branching by corticospinal axons within the spinal cord and later
      diminished the magnitude of branching. These findings indicate a role for PSA in
      the regulation of interstitial axon branching, a crucial step in the process of
      target recognition and innervation by corticospinal axons.

PMID- 8757262
TI  - Retroviral misexpression of engrailed genes in the chick optic tectum perturbs
      the topographic targeting of retinal axons.
AB  - We have investigated the role of the homeodomain transcription factor genes En-1
      and En-2, homologs of the Drosophila segment polarity gene engrailed, in
      regulating the development of the retinotopic map in the chick optic tectum. The
      En proteins are distributed in a gradient along the rostral-caudal axis of the
      developing tectum, with highest amounts found caudally. Previous evidence
      suggests that En-1 and En-2 may regulate the polarity of the rostral-caudal axis
      of the tectum and the subsequent topographic mapping of retinal axons. We have
      tested this hypothesis by using a recombinant replication-competent retrovirus to
      overexpress the En-1 or En-2 genes in the developing tectum. Anterograde labeling
      with the axon tracer Dil was used to analyze the topographic mapping of retinal
      axons after the time that the retinotectal projection is normally topographically
      organized. Overexpression of either En-1 or En-2 perturbed the topographic
      targeting of retinal axons. In En-infected tecta, nasal retinal axons form an
      abnormally diffuse projection with numerous aberrant axons, branches, and arbors
      found at topographically incorrect locations, colocalized with domains of viral
      infection. In contrast, temporal axons did not form a diffuse projection or
      discrete aberrant arbors; however, many temporal axons were stunted and ended
      aberrantly rostral to their appropriate TZ, or in other cases either did not
      enter the tectum or formed a dense termination at its extreme rostral edge. These
      findings indicate that En-1 and En-2 are involved in regulating the development
      of the retinotopic map in the tectum. Furthermore, they support the hypothesis
      that En genes regulate the polarity of the rostral-caudal axis of the tectum,
      most likely by controlling the expression of retinal axon guidance molecules.

PMID- 8757263
TI  - Anatomical demonstration of ocular dominance columns in striate cortex of the
      squirrel monkey.
AB  - The squirrel monkey is the only primate reported to lack ocular dominance
      columns. Nothing anomalous about the visual capacity of squirrel monkeys has been
      found to explain their missing columns, leading to the suggestion that ocular
      dominance columns might be "an epiphenomenon, not serving any purpose"
      (Livingstone et al., 1995). Puzzled by the apparent lack of ocular dominance
      columns in squirrel monkeys, we made eye injections with transneuronal tracers in
      four normal squirrel monkeys. An irregular mosaic of columns, averaging 225
      microns in width, was found throughout striate cortex. They were double-labeled
      by placing wheat germ agglutinin-horseradish peroxidase into the left eye and
      [3H]proline into the right eye. The tracers labeled opposite sets of
      interdigitating columns, proving they represent ocular dominance columns. The
      columns were much clearer in layer IVc alpha (magno-receiving) than IVc beta
      (parvo-receiving). In the lateral geniculate body, the parvo laminae showed
      extensive mixing of ocular inputs, suggesting that increased label spillover
      contributes to the blurred columns in layer IVc beta. The cytochrome oxidase (CO)
      patches were organized into distinct rows, but they bore no consistent
      relationship to the ocular dominance columns. These experiments indicate that
      ocular dominance columns are less well segregated in squirrel monkeys than
      macaques, but they are present. This fact is pertinent to a recent study
      reporting that ocular dominance columns are absent in normal squirrel monkeys,
      but induced to form by strabismus (Livingstone, 1996).

PMID- 8757264
TI  - Expression of normal and mutant huntingtin in the developing brain.
AB  - Huntington's disease (HD) is caused by a genetic mutation that results in a
      polyglutamine expansion in huntingtin. The time course of neuronal loss in the HD
      striatum and other affected brain regions before the onset of symptoms is
      unknown. To determine the potential influence of huntingtin on brain development,
      we examined its expression in the developing mouse and in human control and HD
      brain. By Western blot, huntingtin was detected throughout the adult mouse brain
      and at all stages of embryonic and postnatal brain development. The protein
      increased significantly between postnatal day 7 (P7) and P15, which marks a
      period of active neuronal differentiation and enhanced sensitivity to excitotoxic
      injury in the rodent striatum. Immunoreactivity was found in neurons throughout
      the brain and localized mostly to the somatodendritic cytoplasm and to axons in
      fiber bundles. Staining was variable in different groups of neurons and within
      the same cell population. In developing brain, huntingtin was limited primarily
      to neuronal perikarya. Increased immunoreactivity in large neurons followed the
      gradient of neurogenesis and appeared in the basal forebrain and brainstem by
      embryonic days 15-17, in regions of cortex by P0-P1, and in the striatum by P7.
      In human brain at midgestation (19-21 weeks), huntingtin was detected in all
      regions. The brain of a 10-week-old infant with the expanded HD allele expressed
      a higher molecular weight mutant form of huntingtin at levels comparable to those
      of the wild-type protein. Thus, mutant huntingtin is expressed before neuronal
      maturation is complete. Results suggest that huntingtin has an important
      constitutive role in neurons during brain development, that heterogeneity in
      neuronal expression of the protein is developmentally regulated, and that the
      intraneuronal distribution of huntingtin increases in parallel with neuronal
      maturation. The presence of mutant huntingtin in the immature HD brain raises the
      possibility that neurons may be affected during brain development and possibly in
      the postnatal period when vulnerability to excitotoxic injury is at its peak.

PMID- 8757265
TI  - Trace eyeblink conditioning increases CA1 excitability in a transient and
      learning-specific manner.
AB  - Time-dependent, learning-related changes in hippocampal excitability were
      evaluated by recording from rabbit CA1 pyramidal neurons in slices prepared at
      various times after acquisition of trace eyeblink conditioning. Increased
      excitability (reduced postburst afterhyperpolarizations and reduced spike
      frequency adaptation) was seen as early as 1 hr after acquisition to behavioral
      criterion, was maximal in neurons studied 24 hr later, and returned to baseline
      within 7 d, whereas behavioral performance remained asymptotic for months.
      Neurons were held at -67 mV to equate voltage-dependent effects. No learning
      related effects were observed on input resistance, action-potential amplitude or
      duration, or resting membrane potential. The excitability changes were learning
      specific, because they were not seen in neurons from very slow learning
      (exhibited < 30% conditioned responses after 15 training sessions) or from
      pseudoconditioned control rabbits. Neurons from rabbits that displayed asymptotic
      behavioral performance after long-term retention testing (an additional training
      session 14 d after learning) were also indistinguishable from control neurons.
      Thus, the increased excitability of CA1 neurons was not performance- or memory
      dependent. Rather, the time course of increased excitability may represent a
      critical window during which learning-specific alterations in postsynaptic
      excitability of hippocampal neurons are important for consolidation of the
      learned association elsewhere in the brain.

PMID- 8757266
TI  - Evidence for differential control of posterior hypothalamic, supramammillary, and
      medial mammillary theta-related cellular discharge by ascending and descending
      pathways.
AB  - Single-unit discharge was recorded from cells in the posterior hypothalamic
      nucleus (PH), supramammillary nucleus (SuM), and medial mammillary nucleus (MM)
      during hippocampal theta (theta) elicited by stimulation of the reticular nucleus
      pontis oralis (RPO). In agreement with previously published work, theta-related
      cells in the PH (12 cells) were all classified as tonic theta-ON (increased tonic
      discharge rate during hippocampal theta), whereas those in the SuM (9 cells) and
      MM (15 cells) were all classified as phasic theta-ON (rhythmic discharge, in
      phase with ongoing theta). The effect of RPO stimulation on cell discharge was
      tested after hippocampal theta was abolished by infusion of procaine into the
      medial septum/vertical limb of the diagonal band. The RPO-elicited discharge
      patterns of all PH tonic theta-ON cells and all SuM phasic theta-ON cells
      survived septal procaine infusion. Further, the discharge rate of PH cells and
      the frequency of burst discharge of SuM cells during RPO stimulation both
      increased after the infusion. In contrast, septal procaine infusion abolished the
      RPO-elicited rhythmic discharge pattern in MM phasic theta-ON cells and
      attenuated their discharge rates. These results indicate that the PH and SuM form
      parts of an ascending system mediating hippocampal theta, whereas the MM receives
      (and perhaps relays to other parts of the limbic system) rhythmic input
      descending from the septo-hippocampal system. In addition, PH and SuM receive
      descending inputs that limit the discharge rates of their theta-related cells
      during hippocampal theta.

PMID- 8757268
TI  - Personal contributions to progress in breast cancer research and treatment.

PMID- 8757267
TI  - A diurnal rhythm of stimulatory input to the hypothalamo-pituitary-adrenal system
      as revealed by timed intrahypothalamic administration of the vasopressin V1
      antagonist.
AB  - The mammalian suprachiasmatic nuclei (SCN) contain an endogenous pacemaker that
      generates daily rhythms in behavior and secretion of hormones. We hypothesized
      that the SCN imposes its circadian rhythm on the rest of the brain via a rhythmic
      release of its transmitters in its target areas. Previously, we demonstrated a
      pronounced inhibitory effect of vasopressin (VP), released from SCN terminals in
      the dorsomedial hypothalamus, on the release of the adrenal hormone
      corticosterone. In the present study, microdialysis-mediated intracerebral
      administration of the VP V1-receptor antagonist was used to pursue the study of
      the mechanisms underlying the circadian control of basal corticosterone release.
      Using timed administrations of the VP antagonist divided equally over the
      day/night cycle, we were able to uncover the existence of an additional
      stimulatory input from the SCN to the hypothalamopituitary-adrenal (HPA) axis.
      Peak activity of this stimulatory SCN input takes place during the second half of
      the light period, after the daily peak of VP secretion, with a delay of
      approximately 4-6 hr. In all likelihood, the inhibitory and stimulatory circadian
      input via separate mechanisms affects corticosterone release. Together, these two
      opposing circadian control mechanisms of the HPA axis enable a precise timing of
      the circadian peak in corticosterone release.

PMID- 8757269
TI  - The role of pathology in premalignancy and as a guide for treatment and prognosis
      in breast cancer.
AB  - This review emphasizes tissue pathology and its practical relevance to patient
      management in premalignant breast disease and established breast cancer. The
      rationale and criteria for recognizing benign lesions that indicate a subsequent
      increased risk for cancer development are now well established, having been
      confirmed in several large epidemiologic studies. Our understanding of the
      heterogeneous nature of ductal carcinoma in situ (DCIS) continues to evolve.
      Recent efforts to classify DCIS into clinically meaningful categories underscore
      the central role of histopathology in the management of this disease. Through
      long term follow up studies, small examples of noncomedo DCIS treated by biopsy
      alone may predict local recurrence. Adequate surgical excision, however, avoids
      this possibility in the predominance of such cases. For invasive carcinomas,
      prognostic issues extend beyond predicting survival after local treatment. Now
      that the efficacy of systemic chemotherapy is established, the question is
      whether this therapy will be of use to a particular patient or group of similar
      patients. The list of possible clinically useful subcategories of prediction is
      growing and under active development. Prognostic factors that are in general use,
      having been repeatedly validated, particularly stage and histologic grade, as
      well as those that are emerging but in need of validation, are reviewed.

PMID- 8757270
TI  - Critical evaluation of prognostic factors.
AB  - The ability to predict the biological behavior of breast tumors can allow
      selection of the optimum treatment and follow-up strategies. Conventionally,
      tumor size, lymph node metastases, and histopathologic features have been used to
      determine the risk of systemic relapse. The discovery of a number of specific
      genetic and biochemical alterations in breast tumors has led to the molecular era
      of prognostic factors. Many of these molecular changes are determinants of
      relevant biological characteristics of malignancy, ie, dyregulated proliferation,
      invasion, and metastases. Preliminary data suggest that they may provide a better
      determination of the risk of relapse than can be ascertained by conventional
      prognostic factors alone. For example, amplification/overexpression of HER-2/neu
      oncogene has been shown to be a marker of increased risk of relapse after
      locoregional therapy of breast cancer. More recent studies have shown that it may
      also play a role in determining sensitivity to chemo-therapeutic drugs. It is
      expected that a greater understanding of the molecular basis of breast cancer
      growth regulation will allow a better identification of subjects who should
      receive systemic therapy and will also allow a better selection of the
      appropriate systemic therapy regimen.

PMID- 8757271
TI  - Management of lobular carcinoma in situ and ductal carcinoma in situ of the
      breast.
AB  - Mammographic screening has resulted in an epidemic of diagnoses of ductal
      carcinoma in situ (DCIS). These are often small, impalpable lesions that do not
      reflect the natural history of older series of DCIS found by palpation at a
      larger size. The behavior of DCIS is related to the histological grade and size
      of the tumor. Therapy is primarily surgical excision. Irradiation has been shown
      to halve the rate of recurrence after local excision. Therapeutic decisions
      involving the extent of surgical excision and the addition of irradiation are
      based on considerations of tumor size and grade and the patient's age.

PMID- 8757273
TI  - Primary chemotherapy in operable breast cancer.
AB  - The origins of primary chemotherapy lie in the experience gained more than 20
      years ago in the multimodal treatment for locally advanced breast cancer. Today,
      primary chemotherapy followed by surgery and radiation is emerging almost all
      over the world as a common approach for large but resectable breast cancers. The
      mounting interest for this approach has resulted in increasing number of
      available reports on this subject. Unfortunately, there is remarkable
      heterogeneity among most studies as far as patient selection, locoregional
      treatment, drug therapy, as well as criteria of tumor response and length of
      follow-up are concerned. At present, the most recognized benefit of primary
      chemotherapy is prompt tumor shrinkage, enabling surgeons to increase the use of
      breast-conserving procedures. However, as clinical experience grows, it is
      becoming clear that the most important scope of the early use of full-dose
      chemotherapy is a more effective eradication of systemic micrometastases. This
      review summarizes the current state of knowledge about this multidisciplinary
      approach and outlines future prospects. In conventionally resectable breast
      cancer, innovative prospective controlled studies, well designed and properly
      conducted, are warranted to definitely assess whether the administration of
      primary chemotherapy can further improve the continuous relapse-free survival
      over classical adjuvant systemic treatments.

PMID- 8757272
TI  - Options in the local management of invasive breast cancer.
AB  - Newly diagnosed, early-stage breast cancer confronts the patient and her
      clinician with multiple treatment decisions. This review examines some of these
      local treatment options including the choice between breast-conserving treatment
      (BCT) and mastectomy, how best to treat the axilla, and the optimal sequencing of
      local and systemic therapy. Key elements in the selection of patients for BCT or
      mastectomy include preoperative mammography, careful pathological evaluation, and
      an assessment of patient desires in order to balance the risk of local recurrence
      against preservation of a cosmetically acceptable breast. Although some absolute
      contraindications to BCT exist, most patients are candidates for BCT. The role of
      axillary dissection is currently being redefined, and in the future, more limited
      procedures may be able to identify patients who can avoid axillary dissection.
      The relationship between timing of breast surgery with regard to the menstrual
      cycle and outcome is intriguing but not yet established. As well, the appropriate
      sequencing of chemotherapy and radiotherapy (RT) after conservative surgery (CS)
      is uncertain, although randomized trials are beginning to shed some light on this
      issue. Whether all patients treated with CS require treatment with RT is another
      question that is currently under investigation. This article addresses these
      issues, focusing on the specifics of treatment implementation.

PMID- 8757274
TI  - Adjuvant drug therapy for operable breast cancer.
AB  - Breast cancer-the most common malignancy of lethal potential for women in the
      developed world-presents as two interrelated problems: (1) local disease in the
      breast and axillary lymph nodes, and (2) micrometastatic disease in distant
      sites. During the last century, advances in surgery and radiotherapy have led to
      high rates of control over local disease. In addition, heightened public
      awareness and the more widespread use of mammography have led to the more
      frequent detection of smaller cancers with better prognosis. Nevertheless, the
      problem of distant recurrence, leading almost inevitably to death, persists.
      Hence, there is considerable interest in integrating systemic therapy, which
      since mid-century has been shown to be active against advanced disease, into the
      treatment of primary breast cancer. The long-standing theoretical prediction of
      benefit from drug therapy as an adjunct to local control procedures has now been
      confirmed by several decades of clinical investigation. Long-term follow-up of
      seminal trials and the conduct of a crucial series of meta-analyses have
      established the ability of both hormonal therapies and chemotherapy to prolong
      disease-free and overall survival in nearly all groups of patients. Although the
      relative and absolute influences of drug therapies remain modest, if these were
      properly applied to the hundreds of thousands of patients diagnosed worldwide per
      year, the potential impact on public health would be significant. In addition,
      recent laboratory advances and clinical trial data have indicated several new
      directions that promise greater impact against occult disseminated disease. These
      include novel dosing and scheduling strategies, newer active agents, fresh
      biochemical targets, and different combinations of chemotherapy with hormonal
      therapy.

PMID- 8757275
TI  - Endocrine therapies of breast cancer.
AB  - Endocrine therapies for breast cancer have been used for more than a century. The
      concept that changing the hormonal balance of the patient with breast cancer
      could lead to changes in tumor growth and regression of metastatic disease was
      recognized even before hormones and endocrine agents were available. Ablation of
      ovaries, adrenals, or hypophysis was used in advanced disease to obtain tumor
      regression and control of symptoms. Ovarian ablation was also tested for operable
      breast cancer showing a significant beneficial treatment effect. Several
      endocrine agents have been developed in recent years: estrogens, androgens,
      progestins, antiestrogens, aromatase inhibitors, gonadotropin-releasing hormone
      analogs, antiprogestins, and antiandrogens. The use of some of these agents in
      advanced disease led to investigations in early breast cancer: tamoxifen was the
      drug which was most extensively tested, showing a significant long-term benefit
      for treated patients. Progestins (medroxyprogesterone acetate) and aromatase
      inhibitors (aminoglutethimide) were also tested in a few clinical trials, but no
      conclusive recommendations for their use in patients with operable disease may be
      formulated. The most important current challenges for the appropriate use of
      endocrine therapies in breast cancer include (1) understanding the effect of
      endocrine therapies and the mechanisms of resistance associated with their use;
      (2) developing new agents with novel endocrine antitumor effect; (3) defining the
      best way to combine endocrine agents with cytotoxics or with other endocrine
      manipulations; and (4) identifying long-term effects of endocrine agents in terms
      of disease control and prevention, as well as desirable and undesirable side
      effects.

PMID- 8757276
TI  - New treatments for breast cancer.
AB  - The development of new treatments for breast cancer has been fueled by the
      plateau in median survival which has been observed using standard drugs.
      Chemotherapy scheduling and dose-intensity are areas of intense research. As the
      same time, new drug development has been remarkably productive. Novel agents have
      been evaluated that induce high response rates. Clinical superiority may
      ultimately emerge as new spindle poisons, topoisomerase inhibitors, and
      antifolates are compared with standard therapy. New inhibitors have also been
      developed for hormone sensitive breast cancer. Immunologic therapy has reached
      phase III trials. Novel liposomal delivery systems allow maximum bioavailability
      with minimal toxicity. Finally, palliation of bone pain is now possible with site
      specific agents such as pamidronate and 89Strontium. As the arsenal of treatments
      continues to expand, these new agents are primed to enter clinical practice. If
      current progress continues, the next decade promises exciting hope for the
      treatment of breast cancer.

PMID- 8757278
TI  - Enzymic control of collagen fibril shape.
AB  - The shape of collagen fibrils growing in vitro in a cell-free enzyme/substrate
      system is shown to be dependent on the enzyme/substrate (E/S) ratio. Long fibrils
      with tapered ends were generated by exposing pCcollagen (procollagen from which
      the N-propeptides had been removed) to procollagen C-proteinase (which acts by
      cleaving the C-propeptides from the pCcollagen, converting it to insoluble fibril
      forming collagen). Tip shape profiles, established quantitatively by scanning
      transmission electron microscopy, depended critically on the C
      proteinase/pCcollagen ratio. The finest tips occurred at low ratios, the coarsest
      at high ratios. All fibrils had molecules oriented with amino termini closest to
      the pointed ends, i.e. N,N-bipolar fibrils in which molecules change orientation
      abruptly at one location along the fibril. Fibrils had maximal diameter at this
      molecular switch region. Shape asymmetric fibrils occurred at low E/S ratios,
      near-shape symmetric fibrils occurred at high ratios. Fibrils generated at low
      E/S ratios bore the closest resemblance to those formed in vivo except that the
      central shaft regions of fibrils formed in vitro showed no tendency to be limited
      to a uniform diameter.

PMID- 8757279
TI  - Functional interaction between release factor one and P-site peptidyl-tRNA on the
      ribosome.
AB  - Translation termination at UAG is influenced by the nature of the 5' flanking
      codon in Escherichia coli. Readthrough of the stop codon is always higher in a
      strain with mutant (prfA1) as compared to wild-type (prfA+) release factor one
      (RF1). Isocodons, which differ in the last base and are decoded by the same tRNA
      species, affect termination at UAG differently in strains with mutant or wild
      type RF1. No general preference of the last codon base to favour readthrough or
      termination can be found. The data suggest that RF1 is sensitive to the nature of
      the wobble base anticodon-codon interaction at the ribosomal peptidyl-tRNA
      binding site (P-site). For some isoaccepting P-site tRNAs (tRNA3(Pro) versus
      tRNA2(Pro), tRNA4(Thr) versus tRNA1,3Thr) the effect is different on mutant and
      wild-type RF1, suggesting an interaction between RF1 at the aminoacyl-tRNA
      acceptor site (A-site) and the P-site tRNA itself. The glycine codons GGA
      (tRNA2(Gly)) and GGG (tRNA2,3(Gly)) at the ribosomal P-site are associated with
      an almost threefold higher readthrough of UAG than any of the other 42 codons
      tested, including the glycine codons GGU/C, in a strain with wild-type RF1. This
      differential response to the glycine codons is lost in the strain with the mutant
      form of RF1 since readthrough is increased to a similar high level for all four
      glycine codons. High alpha-helix propensity of the last amino acid residue at the
      C-terminal end of the nascent peptide is correlated with an increased termination
      at UAG. The effect is stronger on mutant compared to wild-type RF1. The data
      suggest that RF1-mediated termination at UAG is sensitive to the nature of the
      codon-anticodon interaction of the wobble base, the last amino acid residue of
      the nascent peptide chain, and the tRNA at the ribosomal P-site.

PMID- 8757280
TI  - Growth rate-dependent control, feedback regulation and steady-state mRNA levels
      of the threonyl-tRNA synthetase gene of Escherichia coli.
AB  - The expression of the gene thrS encoding threonyl-tRNA synthetase is under the
      control of two apparently different regulatory loops: translational feedback
      regulation and growth rate-dependent control. The translational feedback
      regulation is due to the binding of threonyl-tRNA synthetase to a site located in
      the leader RNA of thrS, upstream of the initiation codon, which mimics the
      anticodon stem and loop of tRNA(Thr). This binding competes with that of the
      ribosome and thus inhibits translation initiation. Here, we investigate the
      mechanism of growth rate-dependent control, i.e. the mechanism by which the
      synthetase accumulates at high growth rates. We show that growth rate-dependent
      control acts at the level of translation and requires feedback regulation since
      mutations that abolish feedback regulation also abolish growth rate-dependent
      control. We also show that tRNA(Thr), which accumulates at high growth rates, is
      one of the effectors of growth rate-dependent control since its accumulation can
      cause derepression independently of growth rate. We show that this tRNA(Thr)
      dependent derepression is also dependent on feedback regulation since mutations
      which abolish feedback also prevent derepression. Based on these results and
      previous data concerning the mechanism of translational feedback regulation, we
      propose that threonyl-tRNA synthetase growth rate-dependent control is the
      consequence of the accumulation at high growth rates of two effectors, the
      ribosome and tRNA(Thr). We also study the growth rate-dependence of the steady
      state level of thrS mRNA and show that the steady state level of thrS mRNA
      increases at high growth rates. This increase is dependent on the translational
      feedback regulation and can also be detected, independently of growth rate, when
      thrS mRNA translation is derepressed. Consistently with the model of growth rate
      dependent control above, we propose that at high growth rates, the mRNA is well
      translated and thus stabilised and that, at low growth rates, because of its low
      translation, thrS mRNA is rapidly degraded.

PMID- 8757281
TI  - The global conformation of an active hammerhead RNA during the process of self
      cleavage.
AB  - The RNA "hammerhead" domain is a small element of secondary structure found in
      the genomes of certain plant pathogens. It possesses a core of conserved sequence
      at the conjunction of three helix stems, and is capable of undergoing self
      cleavage in the presence of divalent cations. Both crystallographic and solution
      studies suggest that the domain is highly structured, with the three stems
      assuming a Y-shaped global conformation; however, such studies have employed
      either RNA analogues that were catalytically inactive, or conditions of
      temperature and pH for which rates of self-cleavage are slow. Thus, it was
      unknown whether such species represented the principal conformers during the
      cleavage process itself. In order to address this issue, a series of time
      resolved, transient electric birefringence measurements was conducted in an
      effort to define the global conformation of an RNA hammerhead in real time
      throughout the process of self-cleavage. The current study demonstrates that the
      angular relationship between the two helices that flank the cleavage center is
      essentially unchanged between the pre-cleavage and post-cleavage forms. Moreover,
      despite the fact that at least one kinetic intermediate is formed during the self
      cleavage reaction, there is no evidence for the existence of a significant
      population of intermediates with altered global conformation during cleavage.
      Thus, any conformational isomerism that may occur is likely to be relatively
      localized to the active center. Finally, it was observed that sequence elements
      lying outside of the conserved region, at the base of stem I, influence
      interhelix geometry. The current results are consistent with a structural model
      in which the active center possesses similar conformations pre-cleavage and post
      cleavage. Such a model would help to explain the significant rate of reversal of
      the cleavage reaction (self-ligation).

PMID- 8757282
TI  - Plasmid R6K contains two functional oriTs which can assemble simultaneously in
      relaxosomes in vivo.
AB  - Plasmid R6K contains two functional origins or transfer (oriT), in contrast to
      previously characterized conjugative plasmids. The oriTs are formed by 98 bp
      palindromic sequences invertedly orientated with respect to each other and
      located in the immediate vicinity of the alpha and beta origins of replication.
      The gene for R6K oriT-nickase, taxC, was identified by transposon mutagenesis and
      sequenced, revealing that TaxC belongs to the VirD2 nickase family. The protein
      was overproduced and purified. It catalysed a cleaving-joining reaction on single
      stranded DNA containing its target sequence. Identification of the nic sites
      suggested that the R6K oriTs belong to the RP4/VirD2 oriT family. Cleavage was
      highly specific and did not occur with oligonucleotides cleaved by related
      nickases like TraI of RP4 or VirD2 of the Ti plasmid. nic cleavage of in vivo
      preassembled relaxation complexes was induced by incubation of plasmid cleared
      lysates with ethidium bromide. Nicked molecules obtained in this way were treated
      with snake venom phosphodiesterase to produce double strand cleavages at the nic
      sites. 35% of the molecules were cleaved simultaneously at both nic sites, both
      in the case of R6K and of R6Kdrd1, a derepressed mutant whose frequency of
      transfer is 1000-fold higher. This figure represents the minimum percentage of
      individual R6K molecules containing two pre-assembled relaxation complexes.

PMID- 8757283
TI  - The adenylosuccinate synthetase from the hyperthermophilic archaeon Pyrococcus
      species displays unusual structural features.
AB  - The first example of a hyperthermophilic adenylosuccinate synthetase is reported,
      which is an enzyme that must maintain its folded structure at temperatures as
      high as 102 degrees C. The amino acid sequence of this key enzyme has been
      determined after cloning and sequencing the purA-like gene from the archaeal
      Pyrococcus sp. strain ST700. The corresponding protein displays two unexpected
      features: (1) it is 21% shorter than the homologous mesophilic enzymes and this
      shortening corresponds to the loss of two alpha-helices and three beta-strands
      present in the Escherichia coli enzyme; (2) surprisingly, the archaeal
      adenylosuccinate synthetase has a significant number of substitutions in residues
      that are conserved in all other homologous enzymes from bacteria to man. In E.
      coli, the conserved residues have been described as essential for catalytic
      activity and/or for maintaining the folded structure of the homodimer. Despite
      these drastic differences, the purA-like archaeal gene seems to be normally
      expressed and its product functions in vivo in bacteria, since it complemented an
      E. coli purA auxotroph. The archaeal adenylosuccinate synthetase appears to be a
      good example of a bona fide orthologous protein. Reconstruction of phylogenetic
      trees showed that the archaeal gene is equally distantly related to both
      eukaryotes and bacteria, independently of the numerous substitutions observed at
      critical positions.

PMID- 8757284
TI  - Complete gene map of the plastid-like DNA of the malaria parasite Plasmodium
      falciparum.
AB  - Malaria parasites, and other parasitic protists of the Phylum Apicomplexa, carry
      a plastid-like genome with greatly reduced sequence complexity. This 35 kb DNA
      circle resembles the plastid DNA of non-photosynthetic plants, encoding almost
      exclusively components involved in gene expression. The complete gene map
      described here includes genes for duplicated large and small subunit rRNAs, 25
      species of tRNA, three subunits of a eubacterial RNA polymerase, 17 ribosomal
      proteins, and a translation elongation factor. In addition, it codes for an
      unusual member of the Clp family of chaperones, as well as an open reading frame
      of unknown function found in red algal plastids. Transcription is polycistronic.
      This plastid-like DNA molecule is conserved in several genera of apicomplexans
      and is conjectured to have been acquired by an early progenitor of the Phylum by
      secondary endosymbiosis. The function of the organelle (plastid) carrying this
      DNA remains obscure, but appears to be specified by genes transferred to the
      nucleus.

PMID- 8757285
TI  - The C-terminal SH3 domain of p67phox binds its natural ligand in a reverse
      orientation.
AB  - Src-homology 3 (SH3) domains are small protein modules that bind to proline-rich
      motifs and mediate the formation of signalling complexes. SH3 domains have been
      implicated in the assembly of the phagocyte NADPH oxidase complex, a
      multicomponent enzyme responsible for the production of antimicrobial oxidants.
      Two components of the NADPH oxidase, p67phox and p47phox, each contain two SH3
      domains and we have previously shown that the SH3 domain near the carboxyl
      terminus of p67phox interacts with a proline-rich region of p47phox. In order to
      gain an insight into the specificity of this interaction, a structural model of
      the p67phox SH3 domain has been produced using the known structure of the c-abl
      SH3 domain as a template. The model suggests that the proline-rich ligand of
      p47phox can bind to the SH3 domain in either of two orientations. In each
      orientation, the key residues of the SH3 domain that contact the ligand have been
      identified and altered by site-directed mutagenesis. The ability of the mutated
      SH3 domains to associate with p47phox from cell lysates was tested and the
      results provide the first evidence for the binding of a full-length protein to an
      SH3 domain in a reversed orientation.

PMID- 8757286
TI  - Glycosyl-phosphatidylinositols of Trypanosoma congolense: two common precursors
      but a new protein-anchor.
AB  - The parasitic protozoan Trypanosoma congolense exhibits a dense surface coat
      which is pivotal for immunoevasion of the parasite. This dense surface coat is
      made of a single protein species, the variant surface glycoprotein, which is
      present in a high copy number. The protein is anchored to the plasma membrane by
      a glycosyl-phosphatidylinositol membrane anchor. A detailed study of the
      structure of T. congolense strain 423 (clone BENat 1.3) variant surface
      glycoprotein glycosyl-phosphatidylinositol membrane anchor was performed.
      Radioactively labelled core-glycan prepared by dephosphorylation, deamination and
      reduction was analysed by high-pH anion-exchange chromatography, size-exclusion
      and lectin affinity chromatography. Additionally the glycosyl
      phosphatidylinositol membrane anchor core-glycan was purified from a bulk
      preparation of variant surface glycoprotein and subjected to mass spectrometry
      and methylation analysis. Using these methods we could identify a novel galactose
      beta 1,6-N-acetyl-glucosamine-beta 1,4-branch modifying the mannose adjacent to
      the glucosamine of the mannose-alpha 1,2-mannose-alpha 1,6-mannose-alpha 1,4
      glucosamine core-glycan of the variant surface glycoprotein glycosyl
      phosphatidylinositol membrane anchor. Furthermore the biosynthetic pathway
      leading to this novel structure was investigated. Two putative glycosyl
      phosphatidylinositol anchor precursors were identified having structures
      identical to the previously characterized Trypanosoma brucei brucei glycolipids
      P2 and P3 (also designated glycolipid A and C) consistent with a trimannosyl core
      and a dimyristoyl-glycerol. Both glycosyl-phosphatidylinositol anchor precursors
      of T. congolense do not possess the side-branch modification found on the mature
      protein membrane anchor, implying that the sugar side-chain is added to the
      anchor during its passage through the Golgi-apparatus.

PMID- 8757287
TI  - FliN is a major structural protein of the C-ring in the Salmonella typhimurium
      flagellar basal body.
AB  - The Salmonella typhimurium FliN protein has been proposed to form a mutually
      interacting complex with FliG and FliM, the switch complex, that is required for
      flagellar morphogenesis and function. We have used affinity chromatography for
      purification of extended flagellar basal bodies sufficient for quantitative
      analysis of their protein composition. The belled, extended structure is
      predominantly comprised of the switch complex proteins; with FliN present in the
      most copies (111 +/- 13). This explains why single, missense fliN, fliG or fliM
      mutations, found in many non-motile strains, can alter the belled morphology.
      Cell lysates from these strains contained the wild-type complement of FliG, FliM
      and FliN; but the basal bodies lacked the outer, cytoplasmic(C)-ring of the bell
      and were separated by sedimentation from FliM and FliN. The amount of FliG
      present in basal bodies from wild-type and one such mutant, FliN100LP, was
      comparable. These data show that: (1) the mutations define a FliG and FliMFliN
      multiple contact interface important for motility. (2) FliG is responsible for
      the increased size of the membrane-embedded MS-ring complex of belled relative to
      acid-treated basal bodies. (3) FliN, together with FliM, account for most of the
      C-ring. As a major component of the C-ring, FliN is distinct from the other
      proteins implicated in axial flagellar protein export. Inner, cytoplasmic rod
      basal substructure, seen by negative-stain and quick-freeze replica electron
      microscopy, may gate such export. Lack of connectivity between the cytoplasmic
      rod and ring substructures places contacts between FliG and FliMFliN at the
      periphery of the basal body, proximal to the flagellar intramembrane ring
      particles. This topology is consistent with models where torque results from
      interaction of circumferential arrays of the switch complex proteins with the
      ring particles.

PMID- 8757288
TI  - Motility protein complexes in the bacterial flagellar motor.
AB  - Among the many proteins needed for the assembly and function of bacterial
      flagella, only five have been suggested to be involved in torque generation.
      These are MotA, MotB, FliG, FliM and FliN. In this study, we have probed binding
      interactions among these proteins, by using protein fusions to glutathione S
      transferase or to oligo-histidine, in conjunction with co-isolation assays. The
      results show that FliG, FliM and FliN all bind to each other, and that each also
      self-associates. MotA and MotB also bind to each other, and MotA interacts, but
      only weakly, with FliG and FliM. Taken together with previous genetic,
      physiological and ultrastructural studies, these results provide strong support
      for the view that FliG, FliM and FliN function together in a complex on the rotor
      of the flagellar motor, whereas MotA and MotB form a distinct complex that
      functions as the stator. Torque generation in the flagellar motor is thus likely
      to involve interactions between these two protein complexes.

PMID- 8757289
TI  - Mutations in the peptidyl transferase center of 23 S rRNA reveal the site of
      action of sparsomycin, a universal inhibitor of translation.
AB  - Sparsomycin is a universal and powerful inhibitor of peptide bond formation
      which, in contrast to many other ribosome-targeted antibiotics, does not produce
      footprints on rRNA. A mutant of an archaeon Halobacterium halobium has been
      isolated that exhibits resistance to sparsomycin. Resistant cells possessed a
      mutation in the 23 S rRNA, where C2518 (C2499 in Escherichia coli) was
      substituted by U. Introduction of the C2518U mutation into the chromosomal 23 S
      rRNA gene of wild-type H. halobium rendered cells resistant to sparsomycin,
      demonstrating that a single nucleotide alteration in the rRNA is sufficient to
      confer resistance. Accordingly, ribosomes containing mutant 23 S rRNA exhibited
      increased tolerance to sparsomycin in vitro. Mutations of two other nucleotide
      positions in the peptidyl transferase center, C2471 and U2519 (C2452 and U2500 in
      E. coli), conferred resistance to low concentrations of sparsomycin. The location
      of the sparsomycin resistance mutations reveals the possible site of drug binding
      and/or action. Our findings provide further support for the idea that rRNA may be
      directly involved in interaction with antibiotics and the catalysis of the
      peptide bond formation.

PMID- 8757290
TI  - A sparsomycin-resistant mutant of Halobacterium salinarium lacks a modification
      at nucleotide U2603 in the peptidyl transferase centre of 23 S rRNA.
AB  - Sparsomycin, a broad-spectrum antibiotic, acts at the peptidyl transferase centre
      of the ribosome, stabilizing peptidyl-tRNA binding at the P-site and weakening
      ternary complex binding. A sparsomycin-resistant mutant was isolated for the
      archaeon Halobacterium salinarium and shown to lack a post-transcriptional
      modification of U2603 (Escherichia coli numbering U2584), which is a universally
      conserved uridine base located within the peptidyl transferase loop of 23 S rRNA.
      This mutant also exhibited altered sensitivities to the peptidyl transferase
      antibiotics anisomycin, chloramphenicol and puromycin. Several lines of evidence
      indicate that the unmodified uridine base lies within the P-substrate site of the
      peptidyl transferase centre.

PMID- 8757291
TI  - How proteins recognize the TATA box.
AB  - The crystal structure of a complex of human TATA-binding protein with TATA
      sequence DNA has been solved, complementing earlier TBP/DNA analyses from
      Saccharomyces cerevisiae and Arabidopsis thaliana. Special insight into TATA box
      specificity is provided by considering the TBP/DNA complex, not as a protein
      molecule with bound DNA, but as a DNA duplex with a particularly large minor
      groove ligand. This point of view provides explanations for: (1) why T.A base
      pairs are required rather than C.G; (2) why an alternation of T and A bases is
      needed; (3) how TBP recognizes the upstream and downstream ends of the TATA box
      in order to bind properly; and (4) why the second half of the TATA box can be
      more variable than the first.

PMID- 8757292
TI  - Glycosylated threonine but not 4-hydroxyproline dominates the triple helix
      stabilizing positions in the sequence of a hydrothermal vent worm cuticle
      collagen.
AB  - The cuticle collagen of the vestimentiferan Riftia pachyptila, an organism which
      is endemic to deep-sea hydrothermal vents, has several unusual properties
      including an extraordinary length (1.5 microns), a high thermal stability (37
      degrees C) in spite of a low 4-hydroxyproline content and an atypically high
      threonine content (20 mol%). We have now purified the constituent chain of
      cuticle collagen and show that it contains about 40% carbohydrate, which is
      mainly galactose, indicating that the chain has a molecular mass of approximately
      750 kDa. Several large (30 to 150 kDa) fragments, which all contained
      carbohydrate, could be produced by cleavage with endoproteinase Lys-C, bacterial
      collagenase and cyanogen bromide (CNBr). Edman degradation of these and several
      smaller fragments was used to determine about 3000 sequence positions comprising
      60% of the total triple-helical sequence. This demonstrated mainly typical Gly-X
      Y triplet repeats with a few imperfections and a longer N-terminal non-triplet
      sequence. Most of the 4-hydroxyproline was found in triplet position X, where it
      decreases the stability of the triple helix. About 40% of the Y positions could
      not be identified, which correlated with a low abundance of threonine in the
      sequence and the demonstration of threonine in these positions after
      deglycosylation of several peptides by treatment with hydrofluoric acid. Matrix
      assisted laser desorption ionisation mass spectrometry of selected peptides
      indicated that the blocked threonine residues are occupied by chains of one, two
      or three hexoses (presumably galactose). These glycosylated threonine residues in
      Y positions are therefore likely to replace 4-hydroxyproline as the major
      contributor to triple helix stabilization. Studies with a synthetic (Gly-Pro
      Thr)10 oligopeptide demonstrated a low thermal stability of its triple helix
      which emphasizes a crucial role of glycosylation for stabilization.

PMID- 8757293
TI  - The crystal structure of PR3, a neutrophil serine proteinase antigen of Wegener's
      granulomatosis antibodies.
AB  - The crystal structure of PR3, a serine proteinase from the azurophilic granules
      of human polymorphonuclear neutrophils, has been solved by molecular replacement
      using the human leukocyte elastase structure. The PR3 structure has been refined
      to an R-factor (= sigma parallel Fo magnitude of-Fc parallel/sigma magnitude of
      Fo) of 0.201 for all data in the range of 10.0 to 2.2 A resolution. The enzyme
      was crystallized in space group P21 with four molecules in the asymmetric unit
      (Vm approximately equal to 2.6 A/Da). The overall fold consists of two domains of
      beta-barrel structures typical of the chymotrypsin family of serine proteinases.
      In general, the substrate binding sites, S4 to S3', are more polar than
      comparable sites in the related proteinase, human leukocyte elastase. The
      experimentally observed preference of PR3 for small aliphatic residues at the P1
      position of a substrate is explained by the Val to Ile substitution at position
      190 when compared to the elastase structure. The substitution of Ala by Asp at
      position 213 at the back of S1 should not affect its specificity greatly, as the
      Asp side-chain points back into the interior of the protein. The PR3 structure
      includes a disaccharide unit (N-linked 2-acetamido-2-deoxy-beta-D-glucopyranose
      and 1,6-linked alpha-L-fucopyranose) covalently attached to Asn 159. The linear
      antigenic sites of PR3 reported to react with Wegener's granulomatosis
      autoantibodies occur in regions of the three-dimensional structure that may
      implicate the inactive pro-form of the enzyme in the pathogenesis of the disease.

PMID- 8757294
TI  - Interactions between a helical residue and tertiary structures: helix
      propensities in small peptides and in native proteins.
AB  - We compare three complete sets of helix propensities for the 20 naturally
      occurring amino acids. These propensities are derived from three different
      experimental systems: small synthetic peptides, coiled-coil dimers, and real
      proteins. Thermodynamic analyses show that propensities from the different sets
      should be perfectly correlated if (1) the helix in a protein is formed when and
      only when the protein is folded (tight-coupling); and (2) the amino acid side
      chains are not involved in tertiary interactions. A simple thermodynamic model is
      proposed in order to understand those systems that fail (1). The model
      incorporates fluctuations in both native and unfolded states of the protein.
      Measurements on hydrogen-exchange rate from proteins also question the validity
      of (2). A complementary model that assumes a cooperation between helix formation
      and tertiary structures through side-chain interactions can explain the
      correlation between data from the peptides and proteins. One possible source of
      this side-chain tertiary interaction is the amphiphilicity of helices in
      proteins. Our model is consistent with the ideas of "minimal frustration" and
      "protein malleability"; it exhibits entropy-enthalpy compensation, and suggests
      that local unfolding and solvent penetration are correlated in a fluctuating
      protein. It also suggests experiments to quantitatively verify and differentiate
      between the models. The electrostatic nature of hydrogen bonding and its
      manifestations in protein helix stability is also discussed.

PMID- 8757295
TI  - A functional role for protein cavities in domain: domain motions.
AB  - Motions between individual domains are known to play an important role in protein
      function. Protein cavities at domain interfaces have been suggested to facilitate
      such movements. Consequently, the cavity morphology in a set of multi-domain
      proteins has been critically examined. The conformational changes were well
      characterised by atomic resolution tertiary structures prior to and after domain
      motions. The results showed that interdomain cavities play a number of specific
      functional roles by either facilitating, or being otherwise involved with,
      domain: domain motions. Correspondingly, a higher fraction of cavity surface is
      observed at domain interfaces as compared to that buried within individual
      domains. Furthermore, interdomain cavity-forming residues were found to be highly
      conserved in terms of amino acid residue sequence and volume within their aligned
      protein families, more so than residues exclusive to the domain interface and
      intradomain cavities. These results provide substantial evidence of cavities
      fulfilling a specific functional role in multi-domain proteins.

PMID- 8757296
TI  - The central nervous system as an immunocompetent organ: role of glial cells in
      antigen presentation.
AB  - The central nervous system has the capacity to initiate and regulate immune
      responses by allowing restricted entry of peripheral immune cells and providing a
      microenvironment that is conducive to the activation of immune effector cells. In
      this commentary, we discuss the ability of two glial cell types, astrocytes and
      microglia, to function as APCs. In particular, we focus on the phenotypic and
      functional distinctions between astrocytes and microglia that may contribute to
      their differing abilities to effectively present Ag to CD4+ cells.

PMID- 8757297
TI  - Defective ribosomal products (DRiPs): a major source of antigenic peptides for
      MHC class I molecules?
AB  - MHC class I molecules predominantly bind to peptides derived from a cytosolic
      pool of polypeptides. Little is known about the nature of the polypeptides that
      serve as substrates for peptidogenic cytosolic proteases. We propose that a
      significant source of self and viral peptides are defective ribosomal products
      (DRiPs), which consist of prematurely terminated polypeptides and misfolded
      polypeptides produced from translation of bona fide mRNAs in the proper reading
      frame. DRiPs are produced entropically, due to the inevitable imperfections
      inherent to protein synthesis or folding. To accelerate recognition of cells
      harboring intracellular parasites such as viruses, DRiP formation may be enhanced
      by changes in the cellular physiology induced by infection or by exposure of
      cells to cytokines released at the site of inflammation.

PMID- 8757298
TI  - The responses of mature T cells are not necessarily antagonized by their
      positively selecting peptide.
AB  - Transgenic mice have been produced in which all detectable MHC class II proteins,
      IAb, are bound to a single peptide. Hence, all of the CD4+ class II-restricted T
      cells in these animals are positively selected in the thymus by reaction with
      this single class II/peptide combination. It has been suggested that the peptide
      involved in positive selection of a particular T cell might antagonize the
      responses of that T cell to other peptides, a phenomenon that might serve to
      inhibit autoimmune reactions. To test this idea, we took advantage of the fact
      that T cells from the class II single-peptide mice react strongly in primary
      mixed lymphocyte cultures with IAb molecules from wild-type H-2b mice, i.e.,
      loaded with a heterogeneous collection of self peptides. The responses of the T
      cells to other class II-bound peptides were not inhibited by high concentrations
      of the selecting peptide. Therefore, peptides involved in positive selection of T
      cells do not necessarily inhibit or antagonize the responses of mature T cells to
      Ag.

PMID- 8757299
TI  - Analysis of low zone tolerance induction in normal and B cell-deficient mice.
AB  - To investigate the role of B cells as APCs in acquired tolerance induced by low
      dose soluble protein Ags, normal and B cell-deficient adult mice were injected
      i.v. with repeated low doses (10 microgram) of deaggregated OVA, then challenged
      with OVA in CFA. In animals treated with deaggregated OVA, the in vitro
      proliferative responses of lymph node T cells to OVA were significantly reduced,
      and production of the Th1 cytokine, IFN-gamma, in response to OVA was reduced to
      undetectable levels. This occurred in both normal and B cell-deficient treated
      animals. B cells were also unnecessary for self tolerance of T cells to the
      transgenic self Ag, hen egg lysozyme, in a strain with a very low serum lysozyme
      concentration. Partial low zone tolerance induced by deaggregated, low dose OVA
      was selective for T cell responses as measured by in vitro proliferation and IL-2
      and IFN-gamma production, because Ab responses of B cell-sufficient mice to this
      T cell-dependent Ag were largely unaffected. Both treated and untreated animals
      produced equivalent titers of anti-OVA Abs, predominantly of the IgG1 and IgG2b
      isotypes, following challenge with OVA in CFA.

PMID- 8757300
TI  - Induction of NK activity in murine and human cells by CpG motifs in
      oligodeoxynucleotides and bacterial DNA.
AB  - We have recently shown that oligodeoxynucleotides (ODN) containing unmethylated
      CpG dinucleotides (CpG motif) can induce B cells to proliferate, differentiate,
      and secrete cytokines. In this study we demonstrate that CpG motifs contained in
      ODN as short as 15 bases in length were quite effective at inducing NK cell lytic
      activity in vitro in both human and murine lymphocytes. Such ODN were also
      effective at inducing NK lytic activity, in vivo, in mice. Experiments designed
      to determine the cellular and cytokine requirements for NK cell induction
      revealed that B and T cells are not necessary, that the ODN do not augment the
      activity of highly purified NK cells, and that the ODN augment NK cell activity
      indirectly by inducing the secretion of IL-12, IFN-alpha beta, and TNF-alpha.
      Various ODN sequences were prepared to determine the optimal ODN length, motif,
      palindrome, backbone modification, and dose requirements. We found no requirement
      for a palindromic sequence but a definite requirement for an unmethylated CpG
      motif. While necessary, however, a CpG motif was not sufficient for NK cell
      induction. Instead, there appeared to be stringent requirements for the immediate
      flanking bases at the 5' and 3' ends as well as for flanking sequences outside
      the immediate 5' and 3' bases. In particular poly(G) ends seemed to exert a
      complex qualitative and quantitative effect which could be up- or down-modulating
      depending on whether the ODN backbone was phosphorothioate modified or not.

PMID- 8757301
TI  - Two distinct stimulus-dependent pathways lead to production of soluble murine
      interleukin-4 receptor.
AB  - The IL-4R exists in two forms, either membrane bound or as a soluble (s)
      molecule. Since the sIL-4R binds to its ligand with high affinity, thereby acting
      as an immunoregulatory molecule, we were interested in the processes leading to
      its release. First, the release of sIL-4R in the model of murine leishmaniosis
      was analyzed. Infection of mice with Leishmania major resulted in up-regulation
      of sIL-4R production by Ag-stimulated CD4+ T cells, with a maximum around 7 days
      after infection. To clarify the mechanisms underlying sIL-4R release, in vitro
      studies were performed. After stimulation of naive lymphoid cells with IL-4, sIL
      4R release was dependent on up-regulation of spliced IL-4R mRNA, as shown by
      inhibition with specific antisense oligonucleotides. In contrast to this, no
      increase in the spliced IL-4R mRNA and no inhibitory influence of antisense
      oligonucleotides were observed after stimulation of T cells from IL-4-deficient
      mice with anti-CD3 mAb. Thus, TCR stimulation can lead to IL-4-independent sIL-4R
      production. Under these conditions proteolytic shedding of membrane-bound IL-4R
      appears to be the principal mechanism of release, since in contrast to
      stimulation with IL-4, iodinated sIL-4R could only be immunoprecipitated after
      cell surface labeling and subsequent TCR stimulation. The common gamma-chain, a
      component of the IL-4R complex, did not appear to be involved in the pathways
      leading to sIL-4R expression. This analysis suggests the existence of two
      differentially regulated pathways of sIL-4R release, possibly having different
      consequences for the regulation of IL-4 bioactivity.

PMID- 8757302
TI  - The CD5/CD72 receptor system is coexpressed with several functionally relevant
      counterstructures on human B cells and delivers a critical signaling activity.
AB  - The CD5 molecule is expressed on T cells and, at a lower density, on a minor B
      cell subset (CD5+ B cells). The pan-B Ag CD72 was recently identified as the CD5
      counterstructure, and several data suggest the involvement of this ligand pair in
      T-B cell cognate interaction. However, the functional role of CD5 and CD72
      molecules within the B cell compartment is still unknown. In this work we studied
      umbilical cord blood CD5+ B cells (B-1a), adult splenic CD5- B cells (B-2), and
      CD5+ B cells from patients with chronic lymphocytic leukemia. Flow cytometry
      analysis and proliferation assays were used to determine 1) the ability of B-1a
      and B-2 cells to coexpress functionally relevant counterligands other than CD5
      and CD72, and 2) the signaling capacity of CD5 and CD72 in terms of B cell
      activation and proliferation. To this purpose, freshly isolated or preactivated
      normal and neoplastic B cells were cultured with agonistic anti-CD5 or anti-CD72
      mAbs in the presence or the absence of cytokines equipped with B cell activity.
      Our data demonstrate that CD5 and CD72 molecules are coexpressed with other
      ligand pairs usually involved in T-B cell cognate interaction on B-1a cells, but
      not on B-2 cells. CD5 and/or CD72 engagement delivers critical costimulatory
      signals in B-1a, B-2, and B cells from patients with chronic lymphocytic
      leukemia, but with different requirements and patterns. Besides suggesting the
      potential involvement of B-1a lymphocytes in B-B cell interactions during T
      independent B cell responses, our results indicate that CD5 and CD72
      counterstructures play a functional role in the B cell compartment.

PMID- 8757303
TI  - A novel murine model for the assessment of human CD2-related reagents in vivo.
AB  - CD2 is a T cell surface glycoprotein that mediates both cell-cell adhesion and
      transmembrane signal transduction. To construct a model for the in vivo
      evaluation of human (h)CD2 function and hCD2-related reagents, hCD2 transgenic
      mice and murine (m)CD2 knockout mice were crossed, and the F2 generation selected
      for mCD2-hCD2+ animals by fluorescent flow cytometry. The mCD2-hCD2+ mice are
      healthy and have a normal distribution of mCD3, mCD4, and mCD8 in thymus, spleen,
      and lymph node. Therefore expression of the hCD2 transgene does not appear to
      disrupt normal T cell development. The functionality of hCD2 was demonstrated by
      T lymphocyte proliferation upon stimulation by combined anti-CD2 plus anti-CD2R
      (anti-T11(2) plus anti-T11(3)) mAbs. Anti-T11(2) plus anti-T11(3) anti-human CD2
      mAbs also induced proliferation of mCD2+hCD2+ F1 lymphocytes, but not mCD2+hCD2-
      wild-type murine lymphocytes. Either an anti-murine or the human CD2 specific
      (anti-T11(1)) mAbs inhibited proliferation in alloantigen, PHA, or anti-CD3 mAb
      stimulated cultures and inhibited only cells bearing the appropriate cognate CD2.
      In vivo studies of immune function yielded results consistent with these in vitro
      assays. Thus, anti-T11(1) mAb suppressed contact sensitivity in vivo in the
      transgenic/knockout mice. mCD2-hCD2+ mice treated with anti-T11(1) or LFA-3
      fusion proteins also showed significant prolongation of cardiac allograft
      survival. This prolongation was associated both with depletion and down
      modulation of CD2 on remaining T cells. These data suggest that the
      transgenic/knockout mice provide a useful in vivo model for the assessment of
      hCD2-related reagents and CD2 function, free from any potential interactions with
      mCD2 and mCD2 ligands.

PMID- 8757304
TI  - Neuroendocrine regulation of cytokine production during experimental influenza
      viral infection: effects of restraint stress-induced elevation in endogenous
      corticosterone.
AB  - A murine model of influenza viral infection was used to examine the
      neuroendocrine regulation of cytokine production. Restraint stress (RST) was used
      to activate the hypothalamic-pituitary-adrenal axis and elevate corticosterone
      (CORT) levels in influenza A/Puerto Rico/8/34 (PR8) virus-infected C57BL/6 mice.
      The type II glucocorticoid receptor antagonist RU486 was used to specifically
      examine the modulation of PR8 virus-specific cytokine responses by CORT. RST
      suppressed the PR8 virus- specific production of Th1-type (IL-2 and IFN-gamma)
      and Th2-type IL-10) cytokines by cells from the regional lymph nodes and spleens.
      In addition, IL-6 production by splenocytes was inhibited by RST; however, IL-6
      production by cells from the regional lymph nodes was enhanced. Treatment of mice
      with RU486 prevented the effects of RST, suggesting that the RST-induced
      alterations in cytokine responses were mediated by CORT. Furthermore, CORT was
      shown to inhibit the PR8 virus-specific production of both Thl-type and Th2-type
      cytokines in vitro at doses corresponding to the physiologic range of free plasma
      CORT following hypothalamic-pituitary-adrenal axis activation.

PMID- 8757305
TI  - Intracellular signaling for inducible antigen receptor-mediated Fas resistance in
      B cells.
AB  - CD40 ligand-activated B cells are sensitive targets for CD4+ Th1 effector cells
      that kill in a Fas-dependent fashion. Susceptibility to apoptosis is counteracted
      by Ag receptor binding that produces a state of resistance to Fas engagement in
      otherwise sensitive targets. In the present study, protection from Th1-mediated
      apoptosis was found to be induced by protein kinase C and calcium signals, which
      in combination mimicked the level of Fas resistance produced by surface Ig
      engagement. Signaling for Fas resistance did not alter Fas expression.
      Furthermore, B cells that were protected against Th1-mediated apoptosis were also
      resistant to apoptosis mediated by soluble, rFas ligand. Taken together, these
      results indicate that signaling for protection against Fas-mediated apoptosis
      does not depend on alteration of the interaction between B cell target and Th1
      effector populations. Instead, surface IgM-derived protein kinase C and calcium
      signals appear to produce an intracellular change in the Fas signaling pathway
      that develops over a period of hours and interferes with the apoptotic process
      through a mechanism that depends on protein synthesis.

PMID- 8757306
TI  - Molecular interaction between CD58 and CD2 counter-receptors mediates the ability
      of monocytes to augment T cell activation by IL-12.
AB  - IL-12 stimulates both T and NK cells and is pivotal in the development of the Th1
      immune response. In this work, we show that an interaction between CD2 and CD58
      on activated T cells and monocytes, respectively, regulates the T cell response
      to IL-12. B cells provide little IL-12-specific costimulation, and this
      correlates with the low level of CD58 on B cells relative to monocytes and the
      lack of significant up-regulation in response to IFN-gamma or PHA activation. CHO
      cell transfectants expressing CD58 at a level comparable with that found on
      monocytes restore IL-12 responsiveness to APC-depleted T cells. This effect is
      not observed with CHO cells expressing CD48, a second CD2 ligand with a low
      avidity for CD2 relative to CD58. Thus, in addition to augmenting adhesion
      between T cells and their cognate APCs and facilitating TCR-triggered activation,
      the CD2-CD58 interaction uniquely optimizes the T cell response to IL-12.

PMID- 8757307
TI  - Generation of naturally processed peptide/MHC class I complexes is independent of
      the stability of endogenously synthesized precursors.
AB  - Proteolysis of endogenously synthesized cellular proteins is essential for
      constitutive display of processed peptide/MHC class I complexes on the APC
      surface for stimulating CD8+ T cells. However, the extent to which normal protein
      turnover serves as the source of processed peptides is not clear. To address this
      question, we used pairs of novel N-end rule substrates that varied in their
      intracellular stability and served as precursors for generating peptide/MHC class
      I (OVA257-264/Kb or influenza nucleoprotein 366-374/Db) complexes. Surprisingly,
      although each of three precursor pairs tested varied profoundly in their
      intracellular stability, they were indistinguishable in either T cell stimulation
      assays, or in the amounts of naturally processed peptides in the APC extracts.
      Our findings demonstrate that the proteolytic turnover of endogenously
      synthesized proteins is not directly proportional to the generation of processed
      antigenic peptide/MHC class I complexes.

PMID- 8757308
TI  - Intraocular injection of class II-restricted peptide induces an unexpected
      population of CD8 regulatory cells.
AB  - Intraocular injection of exogenous protein induces an Ag-specific impairment of
      systemic delayed hypersensitivity (DH), termed anterior chamber associated immune
      deviation (ACAID). The ACAID-inducing signal is carried by blood-borne cells from
      the eye to the spleen and can also be generated in vitro by incubating APCs with
      Ag plus TGF-beta. Paradoxically, class I-restricted CD8 regulatory cells are
      induced in the spleens of mice with ACAID, and previous studies suggest that CD8
      cells are important, and even necessary, for the expression of ACAID. To explore
      this issue further, we asked whether ACAID could be induced with a class II
      restricted peptide, and if so, what type of regulatory cells are generated. An
      intraocular, but not an i.v., injection of OVA (323-339) peptide resulted in
      impairment of native OVA-specific DH in both naive and previously sensitized
      mice. Furthermore, i.v. injection of APCs pretreated with TGF-beta plus OVA
      peptide also prevented native OVA-specific DH. Surprisingly, both CD8+ and CD4+
      spleen cells capable of impairing expression of DH were induced by either
      intraocular injection of peptide or i.v. injection of APCs pretreated with
      peptide plus TGF-beta. In summary, ACAID can be induced by a class II-restricted
      peptide and is accompanied by the generation of two unusual populations of cells:
      1) CD8+ regulatory cells unexpectedly induced by class II-restricted peptide; and
      2) a novel population of CD4 regulatory cells induced by peptide, but not native
      protein. Potential mechanisms involved in the processing and presentation of
      exogenous protein in the ACAID model are discussed in light of the present data.

PMID- 8757309
TI  - Reduced IL-12 production by monocytes upon ultraviolet-B irradiation selectively
      limits activation of T helper-1 cells.
AB  - The capacity of APC to stimulate the proliferation of human peripheral blood T
      cells decreases upon ultraviolet-B (UVB) irradiation. The aim of this study was
      to investigate whether all T cell subsets are equally sensitive to this reduced
      APC function. Established human Th1, Th2, and Th0 clones were stimulated with
      monocytes in a soluble CD3 mAb-mediated assay that is dependent on the presence
      of APC. Monocytes were exposed to low nonlethal doses of UVB radiation before
      coculture with T cells. UVB irradiation inhibited the capacity of monocytes to
      stimulate the proliferation and IFN-gamma production of Th1 cells in a dose
      related fashion. In contrast, UVB-treated monocytes induced normal proliferation
      and IL-4 production in Th2 cells. Stimulation of Th0 cell proliferation by UVB
      irradiated monocytes was normal, but a preferential suppression of IFN-gamma
      production was observed, thus leading to a more Th2-like cytokine response. The
      loss of Th1 proliferation upon stimulation with UVB-irradiated monocytes could be
      overcome by rIL-2; however, IFN-gamma production remained suppressed. IFN-gamma
      production could be completely restored by rIL-12, whereas the addition of IL-1
      beta, TNF-alpha, or indomethacin had no such effect, nor did the addition of mAb
      to CD28, added to compensate for the reduced B7 expression of UVB-irradiated
      monocytes. Monocytes exposed to UVB radiation exhibited reduced expression of
      mRNA for the IL-1 2 subunits p35 and p40 and suppressed production of the IL-12
      p70 protein. Our results thus indicate that UVB irradiation of APC selectively
      impairs Th1-like responses, a phenomenon caused by the UVB-induced suppression of
      monocyte IL-12 production.

PMID- 8757310
TI  - Perforin, Fas ligand, and tumor necrosis factor are the major cytotoxic molecules
      used by lymphokine-activated killer cells.
AB  - Lymphokine-activated killer (LAK) cells generated from perforin knockout mice
      possess significantly reduced cytotoxicity against a panel of tumor target cell
      lines, with some tumor cells being lysed exclusively by the perforin pathway. LAK
      cells are also capable of Fas ligand-mediated cytotoxicity. LAK cells generated
      from mice deficient in both perforin and Fas ligand (PKO/gld) were not cytolytic
      in short term cytotoxicity assays, demonstrating that perforin and Fas ligand are
      required for acute target cell lysis. However, PKO/gld LAK cells were cytotoxic
      in long term cytotoxicity assays against TNF-sensitive tumor lines, and this
      cytotoxicity was completely inhibited by neutralizing TNF Abs. This potent TNF
      cytotoxicity has not been fully appreciated previously because of the presence of
      dominant-acting perforin and Fas ligand in acute tumor cell lysis. TNF-based
      cytotoxicity by PKO/gld LAK was both soluble and membrane bound, and both forms
      of TNF were constitutively expressed. Thus, LAK cells are armed with at least
      three cytotoxic molecules: perforin, Fas ligand, and TNF.

PMID- 8757311
TI  - Intraepithelial lymphocytes in human gut have lytic potential and a cytokine
      profile that suggest T helper 1 and cytotoxic functions.
AB  - The functional properties of intraepithelial lymphocytes (IEL) in normal human
      jejunum, ileum, and colon were investigated. Cytokine mRNA expression in IEL and
      enterocytes was determined by reverse transcriptase-PCR and IFN-gamma+ IEL by
      immunohistochemistry. Polyclonal activators were used to study proliferation and
      IFN-gamma secretion of IEL, and an anti-CD3-mediated redirected cytotoxicity
      assay was used to determine the lytic potential of IEL. Freshly isolated IEL at
      all three gut levels expressed mRNA for IL-1 beta, IL-2, IL-8, IFN-gamma, and TNF
      alpha. Approximately 10% of IEL produced IFN-gamma, suggesting that IEL are
      immunologically active in vivo, performing similar functions along the intestine.
      IEL could be stimulated further in vitro to express IL-10, TNF-beta, and TGF-beta
      1, while no Th2-type cytokines were induced, suggesting suppressive and cytolytic
      functions for IEL. All three jejunal IEL subpopulations (CD4-CD8-TCR-gamma
      delta+, CD4+TCR-alpha beta+, CD8+TCR-alpha beta+) expressed the same four
      cytokines, IL-2, IL-8, IFN-gamma, and TNF-alpha, indicating that CD4+TCR-alpha
      beta+ IEL are Th1 cells and that TCR-gamma delta+ IEL and CD8+TCR-alpha beta+ IEL
      include cytotoxic effector cells. Indeed, freshly isolated jejunal IEL displayed
      cytolytic activity. IEL were induced to proliferation by anti-CD3/TCR complex
      mAbs and leukoagglutinin, but not by Con A. There was no correlation between the
      magnitude of the proliferative response and the amounts of secreted IFN-gamma.
      Enterocytes expressed IL-1 beta and IL-8, and sometimes TNF-alpha. Although
      jejunal enterocytes express HLA-DR and hsp60, Ag presentation by these cells may
      induce anergy since their cytokine profile is different from that of classical
      APCs.

PMID- 8757312
TI  - Switching on of the proliferation or apoptosis of activated human T lymphocytes
      by IFN-gamma is correlated with the differential expression of the alpha- and
      beta-chains of its receptor.
AB  - To find out how physiologically secreted IFN-gamma controls either the
      proliferation or the apoptosis of human T lymphocytes, the kinetics of expression
      of the alpha- and beta-chains of its receptor (IFN-gamma R) were sequentially
      followed on T lymphocytes first activated with PHA and then cultured in the
      presence of IL-2, and related to the kinetics of expression of Fas, Bcl-2, and IL
      2R p55 chain. Both IFN-gamma R chains were poorly expressed on the membrane of
      resting T lymphocytes. Following their stimulation with PHA, IFN-gamma R alpha
      but not IFN gamma R beta-chain up-modulated before T lymphocyte entry into the S
      phase, and then IFN-gamma R alpha down-modulated when they passed through the S
      and G2/M. The ensuing proliferative response was inhibited by an anti-IFN-gamma R
      alpha mAb that impeded the binding of IFN-gamma. When PHA-activated T
      lymphoblasts were cultured for 16 days with IL-2, IFN-gamma R alpha expression
      increased, whereas that of the beta-chain remained barely detectable. Fas and Bcl
      2 were both highly expressed. When these T lymphoblasts were restimulated by PHA,
      OKT3, or Staphylococcus enterotoxin beta-pokeweed mitogen, both chains up
      modulated and most cells underwent apoptosis in a way apparently independent of
      Bcl-2, but not of Fas. This apoptosis, too, was prevented by the anti-IFN-gamma R
      alpha mAb. Physiologically secreted IFN-gamma is thus involved in the activation
      of resting T lymphocytes and in the apoptosis of reactivated lymphoblasts.
      However, high expression of IFN-gamma R beta took place when IFN-gamma induced
      apoptosis, but not when it induced proliferation. In conclusion, a correlation
      exists between differential expression of the IFN-gamma R beta-chain and the
      delivery by IFN-gamma of proliferative or apoptotic signals.

PMID- 8757313
TI  - Induction of "infectious" tolerance to MHC-incompatible cardiac allografts in CD4
      monoclonal antibody-treated sensitized rat recipients.
AB  - LBNF1 heart grafts are rejected in an accelerated manner within 36 h by LEW rats
      that have been sensitized with Brown Norway rat skin grafts on day -7. Treatment
      with RIB-5/2, a CD4-nondepleting mAb (10 doses of 5 mg/rat/day, i.v., from day -7
      to day +21) abrogated rejection at <36 h and produced indefinite (>200 days)
      cardiac allograft survival. Transplantation tolerance in this model developed
      within several weeks, and during the maintenance phase (>100 days) it was
      associated with diminished host circulating allo-Ab responses and induction of
      peripheral allospecific T cell unresponsiveness both in vitro and in vivo.
      Tolerant cells in mAb-treated hosts could disable naive or alloimmune cells, so
      that they failed to trigger graft rejection. Moreover, donor-specific and organ
      nonspecific tolerance could be adoptively transferred by spleen cells alone into
      new sets of primary (100%) and secondary (>40%) test recipients. CD4+ T cells
      were instrumental for the induction of such readily transferable tolerance. The
      first and second generation suppressive regulatory cells were also critical for
      the inhibition of allograft recognition by normal or even alloimmune cells.
      Hence, the features of an "infectious" tolerance pathway to minor
      histocompatibility-mismatched skin grafts, originally described in thymectomized
      mice, may be applied to the euthymic primed rats rendered tolerant to fully MHC
      incompatible vascularized organ allografts. Such reprogramming of host cell
      mediated regulatory mechanisms following CD4-targeted therapy adds to our
      appreciation of the potential utility and applicability of infectious tolerance
      in transplant recipients treated with a perioperative course of CD4-targeted
      monotherapy.

PMID- 8757314
TI  - IL-12 antagonism induces T helper 2 responses, yet exacerbates cardiac allograft
      rejection. Evidence against a dominant protective role for T helper 2 cytokines
      in alloimmunity.
AB  - IL-12 promotes Th1 development and inhibits the generation of Th2 by inducing IFN
      gamma production. In several experimental models, Th2 are preferentially induced
      in the absence of IL-12. It was proposed that the preferential induction of Th2
      by IL-12 antagonism would inhibit Th1-driven rejection responses, thereby
      promoting allograft acceptance. To test this possibility, mouse cardiac allograft
      recipients were treated with either anti-IL-12 Abs, or with the IL-12 receptor
      antagonist p40 homodimer. Unmodified rejection is characterized by a Th1
      dominated response, with Th2 cytokines being absent or only weakly expressed
      within the allograft. Though both forms of IL-12 antagonism induced Th2 cytokine
      expression within the allograft, these treatments surprisingly exacerbated graft
      rejection relative to control animals. Interestingly, IL-12 antagonism did not
      inhibit IFN-gamma gene expression or in vivo sensitization of IFN-gamma-producing
      cells. Similar observations were made when IL-12 p40 knockout mice were used as
      allograft donors and recipients, verifying that IL-12 was not required for Th1
      development. Further, IL-12 antagonism was associated with strong expression of
      p40 and weak expression of p35 within the graft. Neither p35 nor p40 mRNAs were
      detectable in control allografts. These data indicate that while IL-12 antagonism
      does induce Th2 cytokine expression within cardiac allografts, Th2 cytokines do
      not play a dominant protective role in the rejection process. Further, the Th2
      inducing activity of IL-12 antagonism is not related to decreased IFN-gamma
      production, but may reflect altered regulation of IL-12 itself.

PMID- 8757315
TI  - CD4 ligand IL-16 inhibits the mixed lymphocyte reaction.
AB  - CD4 participation in TCR/CD3-associated activation through interaction with the
      MHC class II Ags results in formation of a CD4-TCR/CD3 complex capable of maximal
      signal transduction. When CD4 binds to alternative ligands such as HIV-1 gp120 or
      anti-CD4 Abs, Ag stimulation of TCR/CD3 is markedly inhibited, and an
      unresponsive state develops. To determine if the natural CD4 ligand interleukin
      16 also induces unresponsiveness, we tested the effects of rIL-16 on T cell
      proliferation in mixed lymphocyte reactions. rIL-16 suppressed T cell
      proliferation in a dose-dependent manner at concentrations of 10(-11) to 10(-7)
      M. Inhibition of proliferation was present on days 5 to 9 of the mixed lymphocyte
      reaction. rIL-16 did not modulate membrane CD4, significantly change basal
      [3H]thymidine incorporation in resting T lymphocytes, or alter viability. The
      suppressive effect was specifically blocked by preincubation with neutralizing
      anti-rIL-16 mAb or with recombinant soluble CD4. While the expression of IL-2R on
      responder cells was unaffected by rIL-16, the addition of exogenous rIL-2 did not
      restore T cell responsiveness. The unresponsiveness induced by rIL-16 is distinct
      from that of other CD4 ligands in that CD4 and IL-2R expression are unaffected.
      The failure of rIL-2 to restore proliferation suggests that the decrease in T
      cell responsiveness induced by rIL-16 may result from an interruption in the IL
      2R-signaling mechanism. These results may help explain how CD4 delivers both
      activating and inhibitory signals and provides a rationale for the role of IL-16
      in the regulation of immune responses.

PMID- 8757316
TI  - Alpha 4 beta 1 (CD49d/CD29) integrin costimulation of human T cells enhances
      transcription factor and cytokine induction in the absence of altered sensitivity
      to anti-CD3 stimulation.
AB  - The integrin alpha 4 beta 1 can provide a costimulus to induce IL-2 secretion and
      IL-2R expression leading to enhanced proliferation of purified, peripheral blood
      T cells. Similar to expression of IL-2, we demonstrated that recombinant vascular
      cell adhesion molecule-1, when co-immobilized with anti-CD3 mAb, significantly
      enhanced the induction of transcription factors NF-AT, AP-1, and NF-kappa B as
      determined by electromobility shift assays. alpha 4 beta 1 ligation alone had no
      effect on transcription factor binding. The requirements for induction of
      transcription factors reflected the requirements for the secretion of multiple
      cytokines, including IL-2, TNF-alpha, IFN-gamma, and granulocyte macrophage-CSF.
      In contrast to freshly isolated T cells, in vitro-cultured T cells did not
      require costimulation for cytokine secretion in response to anti-CD3 alone.
      Comparison of the dose response to anti-CD3 stimulation demonstrated that half
      maximal induction of IL-2 was achieved using the same dose of anti-CD3 for both
      freshly isolated and cultured T cells. Furthermore, the dose of OKT3 required to
      achieve half-maximal activation was the same using PMA or different
      concentrations of alpha 4 beta 1 ligands. Therefore, costimulation by alpha 4
      beta 1 ligands was not due to stabilization of the interaction of the cells with
      its substrate. We conclude, rather, that alpha 4 beta 1 in freshly isolated T
      cells delivers a distinct signal that synergizes early with signals initiated by
      TCR/CD3 ligation to induce DNA binding of multiple transcription factors required
      for cytokine gene induction.

PMID- 8757317
TI  - Short term treatment with soluble neuroantigen and anti-CD11a (LFA-1) protects
      rats against autoimmune encephalomyelitis: treatment abrogates autoimmune disease
      but not autoimmunity.
AB  - Resistance to autoimmune encephalomyelitis was induced by s.c. infusion of myelin
      basic protein (MBP) in saline in combination with i.p. injections of anti-CD11a
      (LFA-1) mAbs. This treatment induces resistance to EAE induction, which appears
      early and persists for at least one month after treatment. Some MBP-CFA
      challenged resistant rats showed minimal inflammation in the central nervous
      system, which was, however, confined to the meninges of the lower spinal cord.
      Examination of the immune status of MBP-anti-LFA-1 treated rats before
      encephalitogenic challenge failed to reveal any priming when assessed by Ag
      driven proliferation and cytokine production by lymphoid cells, and by
      circulating Ab production. Following challenge of protected rats, lymph node cell
      proliferation to MBP was unaltered, indicating that reactive cells had not been
      deleted or energized. Resistance could not be transferred with lymphoid cells
      from treated rats nor abrogated by cyclophosphamide treatment. In treated rats
      following challenge, there was a shift in the isotype of anti-MBP Ab produced,
      from an IgG2a:IgG1 ratio of 2:1 to 1:1, due to an increase in IgG1 production,
      indicating a possible bias towards a nonpathogenic Th2 CD4+ T cell response. The
      IgG1 Ab was detected early after challenge suggesting that pretreatment had
      indeed primed the animals, and had primed them to go down the Th2 pathway
      following encephalitogenic challenge. The ability to divert immune reactivity
      from a destructive to a nondestructive response could have important therapeutic
      implications for autoimmune disease.

PMID- 8757318
TI  - Fas system-mediated apoptosis suppresses lymphopoiesis.
AB  - The lymphoproliferation (lpr) mutation causes the defective expression of Fas Ag,
      which normally transduces an apoptotic signal into cells. T cells from mice
      homozygous for this mutation overexpress the counter-receptor, Fas ligand. In
      this study, we investigated the effects and regulatory influences attributable to
      Fas ligand overexpression on lymphocyte development to clarify the role of Fas
      system-mediated apoptosis in lymphopoiesis in vivo. Nonirradiated severe combined
      immunodeficient (SCID) mice grafted with a fetal thymus (FT) plus fetal liver
      cells (FLC) from MRL-lpr/lpr mice (Fas Ag-defective mice), or with FT from C3H
      gld/gld mice (Fas ligand-defective mice) plus FLC from C3H +/+ mice, developed
      FLC-derived T and B cells. In contrast, SCID mice grafted with FT from MRL
      lpr/lpr Thy-1.1 mice plus FLC from MRL +/+ Thy-1.2 mice (chimera 1) developed few
      FLC-derived T and B cells in the spleen, and the thymus of the recipients also
      contained few FLC-derived T cells. In addition, when SCID mice grafted with FT
      from MRL-lpr/lpr Thy-1.2 mice (H-2k) were co-transplanted with FLC from C57BL/10
      Thy-1.1 mice (H-2b) (chimera 2), FLC-derived T and B cells developed normally.
      Thy-1.1 + cells from chimera 1 expressed Fas ligand mRNA about threefold higher
      than those from chimera 2, and seven- to eightfold higher than Thy-1.2+ cells
      from SCID mice grafted with FT from MRL +/+ Thy-1.2 mice by Northern blot
      analysis. These findings indicate that overexpression of Fas ligand on T cells
      significantly impairs both T and B cell development. Furthermore, the Fas ligand
      overexpression sufficient to impair lymphopoiesis appears to require MHC
      restricted T cell activation. These results suggest that the Fas system
      suppresses lymphopoiesis in vivo.

PMID- 8757319
TI  - Coexpression of B7-1 and antigen blocks tolerance induction to antigen presented
      by resting B cells.
AB  - To investigate a role for B cells as tolerogenic APCs in peripheral lymphoid
      organs, we have developed a system in which B cells from mice transgenic for the
      membrane-bound form of human mu-chain are transferred into nontransgenic
      recipients. Mice injected with B cells expressing human mu-chain became
      profoundly tolerant to human mu-chain, as shown by greatly reduced Ab responses
      following challenge with human mu-chain in adjuvant. Adoptive transfer
      experiments showed that the recipient's Th cell response to human mu-chain was
      impaired. When the human mu transgenic spleen cells were activated with LPS
      before transfer, they no longer induced tolerance. Spleen cells from double
      transgenic mice expressing both human mu-chain and the costimulatory molecule B7
      1 (CD80) also failed to induce tolerance to human mu-chain. However, neither
      human mu transgenic LPS blasts nor double-transgenic B cells induced an Ab
      response or primed for a secondary Ab response to Ag in adjuvant. Therefore, we
      find that expression of B7-1 together with Ag can interfere with tolerance
      induction without inducing Ab formation or priming for a secondary Ab response.

PMID- 8757320
TI  - Avidity maturation, repertoire shift, and strain differences in antibodies to
      bacterial levan, a type 2 thymus-independent polysaccharide antigen.
AB  - Our previous studies of 102 mAb from mice injected with bacterial levan (BL), a
      beta(2-->6) linked polyfructosan with beta(2-->1) branch points (inulin
      determinant, In) showed that BALB/c and CBA/Ca mAb differed in VH and VL gene
      family usage and fine specificity. We now show that BALB/c and CBA/Ca mAb used
      different VHJ606 germ-line genes in response to BL: V14A in BALB/c and a
      previously unidentified gene in CBA/Ca. CBA/Ca mice were found to lack the BALB/c
      V14A gene. Also, we have compared the responses to one (primary, 1 degree) or two
      (secondary, 2 degrees) injections of polysaccharide. The secondary BALB/c anti-BL
      panel has been expanded to a total of 22 mAb, and we report here the isotype,
      fine specificity, and VH/VL usage of the new mAb. Eight of nine primary BALB/c In
      binding mAb were germ-line, whereas both secondary BALB/c In-binding mAb that
      were sequenced differed from the BALB/c germ-line gene V14A. Germ-line primary
      mAb were low avidity whereas all five secondary mAb and the one non-germ-line
      primary were high avidity. There was also a repertoire shift from approximately
      90% VHJ606/V kappa 11 in primary mAb to only 50% in secondary mAb (p = 0.002).
      The data presented provide evidence that avidity maturation and repertoire
      shifts, features usually associated with a memory response to thymus-dependent
      Ags, also can occur in response to a second immunization with a thymus
      independent type 2 polysaccharide Ag.

PMID- 8757321
TI  - Interaction of anti-cholesterol antibodies with human lipoproteins.
AB  - Inoculation of mice with cholesterol-rich liposomes containing the adjuvant
      monophosphoryl lipid A results in the production of antiserum containing IgM Ab
      to cholesterol. The specificity of the Ab was to cholesterol and structurally
      similar sterols containing a 3 beta-hydroxyl group. Anti-cholesterol binding
      activity was significantly diminished if the 3 beta-hydroxyl was altered by
      either epimerization, substitution, oxidation, or esterification. A similar
      specificity for 3 beta-hydroxy-sterols was observed for an anti-cholesterol IgM
      mAb. Both hyperimmune serum and the mAb reacted with intact human very-low
      /intermediate-density lipoprotein (VLDL/IDL) and low-density lipoproteins (LDL),
      but not high-density lipoproteins (HDL), in an ELISA, but could react with total
      lipid extracts containing cholesterol that were prepared from all three
      lipoprotein classes. Functionally, immune serum or the mAb aggregated and induced
      a fusion-like reaction with VLDL/IDL and LDL at low temperatures: these
      aggregates result in spherical structures visible with light microscopy.
      Similarly, binding of anti-cholesterol A to small cholesterol-rich liposomes
      resulted in the appearance of vesicular structures with approximately 20- to 200
      fold increased diameters. These data demonstrate that the anti-cholesterol Ab
      recognize unesterified cholesterol in VLDL/IDL and LDL; high-density lipoprotein
      cholesterol in the intact lipoprotein, however, appears to be protected from
      reaction with these Ab.

PMID- 8757322
TI  - TCR-mediated adhesion of T cell hybridomas to planar bilayers containing purified
      MHC class II/peptide complexes and receptor shedding during detachment.
AB  - T cell recognition of foreign Ag/MHC class II complexes is sensitive down to
      approximately 100 complexes per cell or approximately 0.2 complexes/micron2. To
      better understand the physical basis of the recognition stage of Ag presentation,
      we examined adhesion of the lysozyme- specific T cell hybridoma, 3A9, to
      artificial bilayers containing covalent MHC class II/peptide complexes or
      adhesion molecules. Adhesion of 3A9 cells required a superphysiologic density of
      the MHC class II/peptide complex and was partly dependent on CD4; cells adhered
      but did not crawl. No adhesion was observed to bilayers containing MHC class II
      molecules without the lysozyme peptide. Activated 3A9 cells adhered and crawled
      on bilayers containing ICAM-1. The physical strength of contacts was tested with
      fluid shear. 3A9 cells adherent to bilayers containing MHC class II/peptide
      complexes shed their contact, which remained on the substrate and contained TCR.
      In contrast, 3A9 cells peeled from the ICAM-1 bilayer, and held firmly on LFA-1
      bilayers; in a manner dependent on filamentous actin. When ICAM-1 and the
      MHC/peptide complexes were combined, the 3A9 cells adhered tightly and spread,
      but did not crawl, on the bilayers and TCR clustered at the center of the contact
      area. Physiologically, the TCR is unlikely to directly initiate adhesion. TCR
      clusters formed with the assistance of adhesion mechanisms may have to be shed to
      allow de-adhesion, and this may contribute to TCR down-regulation.

PMID- 8757323
TI  - Structure of the gene encoding the rat T cell ecto-ADP-ribosyltransferase RT6.
AB  - Cellular functions, such as the cytolytic potential of CTLs, can be regulated by
      mono-ADP-ribosylation of target proteins. Recently, the T cell differentiation
      marker RT6 has been shown to possess mono-ADP-ribosyltransferase activity.
      Defects in RT6 expression coincide with increased susceptibility in animal models
      for insulin-dependent diabetes mellitus and other autoimmune diseases. We present
      an analysis of the rat RT6 gene, providing a basis for studying the regulation of
      this gene in T cells of normal and diabetes-prone rats. It is the first
      structural analysis of a mammalian mono-ADP-ribosyltransferase gene. The RT6 gene
      consists of eight exons spanning approximately 20 kb. The proximal four exons
      encode 5' untranslated region sequences and are found in multiple alternatively
      spliced variants. Exon 5 encodes the N-terminal signal sequence. An unusually
      large exon 7 encodes the entire native polypeptide. The final exon 8 encodes the
      C-terminal signal sequence for glycosylphosphatidylinositol anchor attachment and
      the 3' untranslated region. Two independent TATA box-containing promoters
      associated with exons 1 and 2 were identified, and their activity was verified in
      transient transfection assays. The distal promoter displays elements contained in
      the regulatory regions of T cell-specific genes, such as ets and ikaros. Analysis
      of RT6 transcripts showed that this promoter is the major one in adult rat spleen
      cells. The 3' end of the gene does not display alternative splicing. However, two
      polyadenylation signals are found in the 3' untranslated region.

PMID- 8757324
TI  - Ig light chain gene in the Siberian sturgeon (Acipenser baeri).
AB  - Elasmobranch and teleost fish have their Ig light (L) chain loci organized in
      multiple clusters (VL-JL-CL). The VL segments of teleosts are in opposite
      transcriptional orientation to the CL genes, suggesting that in teleosts and
      elasmobranchs there may have been separate evolutionary events leading to this
      organization. To address this problem, the IgL locus from the Siberian sturgeon
      (Acipenser baeri) (representative of a branch between elasmobranchs and teleosts)
      was investigated. Sequence analysis of cDNA clones shows that sturgeon VL genes
      are most similar to those of teleosts, but that sturgeon CL genes are more
      similar to those of the sharks. Southern blot analyses of sturgeon erythrocyte
      DNA with VL- and CL-specific probes showed that there are more than 20 VL
      segments in both the tetraploid Siberian sturgeon and the diploid sterlet
      (Acipenser ruthenus), but only a few CL segments in the genome of the Siberian
      sturgeon and up to four CL segments in that of the sterlet. Screening of an
      unamplified genomic library gave more than 300 VL-positive and four CL-positive
      clones. None of these contained inserts positive for both probes. PCR analysis of
      a genomic CL clone using IC and CL-specific primers suggested that upstream of
      the CL segment there are at least seven JL segments. it is concluded that
      sturgeons have a kappa-like organization of their IgL locus and that the
      clustered organization of IgL loci in bony fish and sharks arose from two
      distinct evolutionary events.

PMID- 8757325
TI  - Transmembrane-4 superfamily proteins CD81 (TAPA-1), CD82, CD63, and CD53
      specifically associated with integrin alpha 4 beta 1 (CD49d/CD29).
AB  - Anti-alpha 4 integrin mAb coprecipitated CD81 (TAPA-1), a 25-kDa cell surface
      protein, from various alpha 4 beta1 -positive hemopoietic cell lines, including
      Molt4, Jurkat, Ramos, and alpha 4-transfected K562 (KX4C4) cells. In reciprocal
      experiments, the integrin alpha 4 beta 1 (VLA4, CD49d/CD29) could be
      reprecipitated from CD81 immunoprecipitates. Anti-alpha 4 integrin mAb also
      coprecipitated CD81 from the alpha 4 beta 7-positive B cell line RPMI 8866. In
      contrast, no CD81 was identified in alpha 2 beta 1, alpha 5 beta 1, or alpha L
      beta 2 immunoprecipitates. Abs to other members of the transmembrane-4
      superfamily, including CD53, CD63, and CD82, also coprecipitated alpha 4 beta 1.
      As shown by confocal microscopy, CD81 and CD82 colocalized with alpha 4 beta 1 in
      cell surface clusters. The cytoplasmic domain of the alpha 4 integrin was not
      necessary for alpha 4 beta 1/CD81 association, nor was the association influenced
      by divalent cations, EDTA, integrin-activating mAb, or alpha 4 subunit cleavage.
      Notably, two independent alpha 4 adhesion-deficient mutants (D346E and D408E)
      were deficient in their ability to associate with CD81. Thus, CD81 and other
      transmembrane-4 superfamily members may participate in functionally relevant
      interactions with alpha 4 beta 1 and other integrins.

PMID- 8757326
TI  - Defective transcription of the IL-2 gene is associated with impaired expression
      of c-Fos, FosB, and JunB in anergic T helper 1 cells.
AB  - Anergic CD4+ Th cells do not produce IL-2 when challenged with Ag-pulsed
      accessory cells because of a transcriptional defect. In this work, we report that
      these anergic T cells are defective in their ability to up-regulate protein
      binding and transactivation at two critical IL-2 DNA enhancer elements: NF-AT
      (nuclear factor of activated T cells; a sequence that binds a heterotrimeric
      NFATp, Fos, and Jun protein complex) and Activator Protein-1 (AP-1) (that binds
      Fos and Jun heterodimers). Western blot analysis of nuclear extracts showed that
      the impaired DNA-protein interactions in anergic T cells were associated with
      poor expression of the inducible AP-1 family members c-Fos, FosB, and JunB.
      However, the reduced expression of these proteins was not the result of a global
      TCR/CD3-signaling defect because CD3 cross-linking induced an equivalent increase
      in intracellular-free calcium ions, as well as NFATp dephosphorylation,
      translocation to the nucleus, and DNA binding in both normal and anergic T cells.
      Thus, defective IL-2 gene transcription appears to be due, at least in part, to a
      selective block in the expression of the AP-1 Fos and Jun family members in
      anergic T cells.

PMID- 8757327
TI  - IL-4-induced expression of the IL-1 receptor antagonist gene is mediated by
      STAT6.
AB  - IL-4 alone or in cooperation with LPS can induce the expression of the gene
      encoding the secreted-type IL-1 receptor antagonist (sIL-1ra) in mononuclear
      phagocytes. To determine the nuclear signaling mechanisms involved in this
      response, the region flanking the transcription start site of the human sIL-1ra
      gene was placed upstream of the luciferase reporter gene, and the function of
      specific sequence elements was analyzed following transient transfection in the
      macrophage-like cell line RAW264.7. A region located between -250 and -200 bases
      relative to the transcription start site was necessary for response to IL-4 alone
      and for cooperation between IL-4 and LPS. This 50-bp region contains two inverted
      repeat elements that represent potential binding sites for members of the signal
      transducer and activator of transcription (STAT) gene family (STAT-binding
      elements (SBEs)). Site-directed mutagenesis of the distal SBE abolished IL-4
      responsiveness, and multiple copies of this motif were able to confer IL-4
      sensitivity to luciferase expression in the context of a heterologous (herpes
      virus thymidine kinase) promoter. Mutation of the proximal SBE in the intact IL
      1ra promoter had little or no effect on response to IL-4, and this sequence motif
      was inactive when examined alone. Electrophoretic mobility shift assays using an
      oligonucleotide corresponding to the distal SBE identified a single binding
      activity that was detected in nuclei within 15 min of IL-4 treatment and that was
      recognized by Ab to STAT6. These results indicate that IL-4-induced STAT6 is
      required for IL-4-induced transcriptional activation of the sIL-1ra gene.

PMID- 8757328
TI  - Contribution of heavy chain junctional amino acid diversity to antibody affinity
      among p-azophenylarsonate-specific antibodies.
AB  - We showed previously that heavy chain gene junctional amino acid differences
      among unmutated p-azophenylarsonate (Ars) Abs that share a unique gene segment
      combination encoding these V regions, termed "canonical," alter affinity. To
      determine the contribution of junctional amino acid differences to binding, we
      introduced, by site-directed mutagenesis, various amino acids at position 100
      and/or 107 (sequential numbering) into the unmutated Ab 36-65. Among 22 mutant
      Abs, 15 preserved or showed increased Ars binding (1-to 12.9-fold increase)
      relative to Ab 36-65, while 7 Abs exhibited lower affinity (< or = 0.5-fold). As
      much as a 150-fold difference in Ars binding was observed between 2 Abs with
      different sets of junctions (Asn100/Tyr107 and Val100/Lys107). Thus, amino acid
      replacements at D gene junctions can produce changes in affinity greater than
      those for any V region somatic mutation observed thus far in vivo among anti-Ars
      Abs and, potentially, can result in preferential selection of Abs containing
      certain junctions during affinity maturation. We combined five different
      junctional residue pairs with mutations at H chain positions 58 and 59 that are
      known to be recurrent in vivo and are associated with increased Ars affinity. The
      mutant Abs all showed increased affinity, indicating that despite variation in D
      gene junctions of Ars-binding canonical Abs, the combined mutations are additive
      for enhancement of Ars affinity. These additive effects reflect the
      "adaptability" of the canonical gene segment combination in sustaining somatic
      mutations leading to affinity maturation.

PMID- 8757330
TI  - Mechanisms of cellular penetration and nuclear localization of an anti-double
      strand DNA autoantibody.
AB  - An anti-dsDNA Ab, mAb 3E10, was identified that bound membranes of fixed human
      renal tubular cells, penetrated live murine renal tubular cells in vivo, and
      localized in the cell nucleus. mAb 3E10 binds both dsDNA and an extracellular
      matrix protein, HP8/HEVIN, expressed in high endothelial venules. Previous
      studies showed both shared and distinct binding determinants of mAb 3E10 VH for
      DNA and HP8/HEVIN. To independently assess the requirement of DNA and HP8/HEVIN
      in cellular penetration, site-directed mutants of mAb 3E10 VH and V kappa were
      studied for penetrating kidney cell lines. The results showed that residues
      required for binding DNA, but not HP8/HEVIN, were necessary for Ab penetration,
      indicating that cellular penetration required the presence of DNA or binding of
      Ab to a membrane determinant precisely resembling DNA. Ab Fab penetrated cells,
      indicating that neither the Fc nor multivalent Ab binding is necessary for
      cellular penetration. Ab synthesized in the cytoplasm as a result of deleting
      heavy and light chain signal peptides was not translocated to the nucleus,
      indicating a mechanism distinct from the usual protein nuclear localization
      signals and suggesting the need for a membrane-mediated pathway or for post
      translational modification of the Ab.

PMID- 8757329
TI  - Regulation of IgM and IgD heavy chain gene expression: effect of abrogation of
      intergenic transcriptional termination.
AB  - Early IgM+ B cells express little or no membrane IgD due to the low abundance of
      delta mRNA. Extensive transcriptional termination regulated by sequences in the
      intronic region between mu and delta heavy chain genes may be the primary reason
      for the lack of delta gene transcription. We have examined the effect of deletion
      of these sequences on the regulation of IgM and IgD heavy chain gene expression
      in transfectants as well as mice carrying this otherwise intact transgene. By run
      on transcriptional measurement, we show that the delta exons are transcribed in
      bone marrow B cells from these transgenic mice. However, in spite of the induced
      premature synthesis of the full-length mu-delta transcript in pre-B cells,
      processing to delta mRNA does not occur until the lymphocytes express cell
      surface IgM. Therefore, during B cell development, synthesis of the full-length
      transcript is a necessary but not sufficient condition for initiation of delta
      mRNA synthesis. Furthermore, unexpectedly, the abrogation of transcriptional
      termination was found to also affect the processing of the primary transcript to
      microM mRNA. These results show that expression of IgD in primary B cells is
      stringently regulated and closely linked to IgM expression.

PMID- 8757331
TI  - In vitro induction of MUC-1 peptide-specific type 1 T lymphocyte and cytotoxic T
      lymphocyte responses from healthy multiparous donors.
AB  - We have recently provided evidence that there is a natural immunization against
      human cancer-associated MUC-1 mucin epitopes during pregnancy by studying MUC-1
      Ag-specific T cell lines established from multiparous women. Using this
      experimental model system, we now report that MUC-1 peptide-specific MHC class I
      restricted CTLs can be generated in vitro using T cells from multiparous women
      stimulated with synthetic MUC-1 peptide-loaded, autologous APCs. The complexity
      of cytokines produced in response to the MUC-1 peptide by anti-MUC-1 T-cells was
      examined. IFN-gamma was generated by MUC-1-specific T cell lines in long term
      cultures, whereas in short term cultures, both IFN-gamma and IL-4 were produced.
      The presence of MUC-1-reactive T cells in multiparous women is consistent with
      their potential role in immune surveillance and provides a rationale for the use
      of certain synthetic MUC-1 peptides for active specific immunotherapy of human
      carcinomas.

PMID- 8757332
TI  - Human gamma delta T cell subset-proliferative response to malarial antigen in
      vitro depends on CD4+ T cells or cytokines that signal through components of the
      IL-2R.
AB  - We examined the cellular and molecular basis of the proliferative response of
      human gamma delta T cells in cultures of PBMC stimulated with blood-stage
      Plasmodium falciparum malarial Ag. Flow cytometry revealed that maximal gamma
      delta T cell proliferation occurs after maximal CD4+ alpha beta T cell
      proliferation. Depletion of CD4+ T cells from PBMC before stimulation with
      malarial Ag markedly reduces the number of proliferating gamma delta T cells,
      which suggests that CD4+ T cells function in providing help to gamma delta T
      cells to respond to this parasite Ag. Removal of gamma delta T cells, however,
      did not alter the expansion of the CD4+ T cell subset. The addition of exogenous
      IL-2, IL-4, or IL-15 restored the capacity of gamma delta T cells to proliferate
      in Ag-stimulated cultures of PBMC depleted of CD4+ T cells. mAbs specific for the
      alpha- and beta-subunits of the IL-2 receptor inhibit the gamma delta T cell
      subset expansion in cultures stimulated with malarial Ag. Taken together, these
      findings suggest that the proliferation of gamma delta T cells in response to
      malarial Ag is dependent on the presence of CD4+ alpha beta T cells, but the
      requirement for CD4+ alpha beta T cells can be met by cytokines that use the IL
      2R.

PMID- 8757333
TI  - IL-15 augments CD8+ T cell-mediated immunity against Toxoplasma gondii infection
      in mice.
AB  - Cytokines of the Th1 profile are important mediators of protective host immunity
      against Toxoplasma gondii infection in mice. In this study we describe the effect
      of the recently identified cytokine, IL-15, on prevention of murine infection
      with T. gondii. Administration of exogenous rIL-15 with soluble Toxoplasma lysate
      Ag (TLA) provides complete protection against a lethal parasite challenge,
      whereas treatment with either rIL-15 or TLA alone is not protective. Following
      immunization with TLA/rIL-15, there is a significant proliferation of splenocytes
      expressing the CD8+ phenotype in response to TLA. A significant rise in the level
      of serum IFN gamma was observed in vaccinated mice. Adoptive transfer of CD8+ T
      cells, but not CD4+ T cells, from TLA/rIL-15-vaccinated mice protects naive mice
      from a lethal parasite challenge. These CD8+ T cells exhibit enhanced CTL
      activity against target macrophages infected with T. gondii. Mice that have been
      immunized are protected against lethal parasite challenge for at least 1 mo
      postvaccination. These observations demonstrate that TLA when administered with
      exogenous rIL-15 generates toxoplasmacidal Ag-specific CD8+ T cells. These T
      cells proliferate upon exposure to parasite Ag, exhibit long term memory CTL
      against infected target cells, and may be involved in host immune memory to this
      parasite.

PMID- 8757335
TI  - Macrophages ingest and are activated by bacterial DNA.
AB  - Recent evidence suggests that bacterial DNA activates immune responses. Here we
      showed that TNF-alpha mRNA was induced in bone marrow-derived macrophages and the
      macrophage cell line RAW 264 by plasmid DNA, but not by DNaseI-digested plasmid,
      plasmid methylated on CpG dinucleotides, or by vertebrate genomic DNA, which is
      naturally largely methylated on these sequences. Synthetic polynucleotides poly
      d(I-C) and poly I x poly C also induced TNF-alpha. IL-1 beta and plasminogen
      activator inhibitor-2 mRNAs were induced by plasmid DNA, and IFN-gamma-pretreated
      macrophages responded to DNA with induction of inducible nitric oxide synthase.
      The HIV-1 long terminal repeat was activated by exogenous DNA in a manner similar
      to TNF-alpha, and was also activated by a CpG-containing oligonucleotide.
      Transcription factor nuclear factor-kappa B (NF-kappa B) is involved in
      regulation of the HIV-1 long terminal repeat and many inflammatory response
      genes. NF-kappa B binding activity was increased by plasmid DNA. An important
      question is whether these effects involve DNA binding to a cell surface receptor
      that signals to the interior, or whether internalization is necessary. Here we
      found that plasmid was taken up by RAW 264 cells and remained sufficiently intact
      to code for luciferase protein. Results suggest that DNA is taken up by
      macrophages and characteristic bacterial DNA sequences, which include an
      unmethylated CpG sequence, activate a signaling cascade leading to activation of
      NF-kappa B and inflammatory gene induction. Relevance to DNA vaccination, gene
      therapy, antisense, and transfection studies is discussed.

PMID- 8757334
TI  - Human monocytes induce a carcinoma cell line to secrete high amounts of nitric
      oxide.
AB  - Nitric oxide (NO) is a short-lived pleiotropic mediator with a multitude of
      biologic functions. The inducible form of NO synthase (iNOS) is responsible for
      the discontinuous production of high amounts of NO and is important for the
      cytotoxic capacity of macrophages in rodents, whereas NO production by human
      macrophages or monocytes (MO) is under debate. Here we report that high amounts
      of NO are synthesized in cocultures of human MO with the human carcinoma cell
      line RT4 without further stimulation. Both cell types have to be viable and
      metabolically active for NO production. However, in contrast to reports by
      others, we could demonstrate that tumor cells and not MO are the producers of NO
      by the following findings: 1) NO release was induced in RT4 cells, but not in MO,
      by diluted supernatants (SN) of RT4/MO cocultures; 2) SN of MO stimulated with
      tumor cell membrane preparations were sufficient to induce NO release by tumor
      cells; and 3) NOS mRNA expression could be detected only in tumor cells, not in
      MO. Separating both cells by a cell-impermeable membrane resulted in NO amounts
      comparable to those in cocultures with direct cell contact, indicating one or
      more soluble NO-inducing factors. Considerable amounts of IL-1 beta and TNF-alpha
      were present in cocultures. IL-1 beta and TNF-alpha, mediators produced by
      activated MO, in combination induce NO release in RT4 cells. Blocking of TNF
      alpha or IL-1 in SN inhibited NO release in RT4 cells. This indicates that IL-1
      beta and TNF-alpha play prominent roles in iNOS induction by MO in RT4 tumor
      cells.

PMID- 8757336
TI  - Rat peritoneal mast cells produce IFN-gamma following IL-12 treatment but not in
      response to IgE-mediated activation.
AB  - Mast cells have been reported to secrete a wide range of immunoregulatory
      cytokines following IgE-mediated activation and to play an important role in
      allergic inflammation. We have previously demonstrated that mast cells can also
      produce certain cytokines following activation with bacterial LPS or prostanoids
      without preformed mediator release. IL-12 is a potent inducer of IFN-gamma
      production by T cells and NK cells, and is thought to play a critical role in
      determining the nature of the local immune response to infection. We here report
      that highly purified peritoneal mast cells from Brown Norway rats will produce
      IFN-gamma in response to IL-12 without significant histamine release. IFN-gamma
      protein was detected by ELISA in supernatants of mast cells cultured with 2 U/ml
      recombinant mouse IL-12 for between 6 and 24 h. The production of IFN-gamma was
      dependent on the dose of IL-12 and was significantly inhibited by concurrent
      treatment with IL-10 or PGE2. Supernatants from IL-12-stimulated mast cells
      induced MHC class II expression on the mouse epithelial cell line, MODE-K, by an
      IFN-gamma-dependent mechanism. Peritoneal mast cells cultured following
      activation with anti-IgE or LPS, under conditions that will induce the production
      of IL-6, demonstrated no detectable protein production of IFN-gamma. We conclude
      that mast cells are capable of contributing to the IFN-gamma response to IL-12,
      but substantial mast cell IFN-gamma production does not occur as a result of IgE
      mediated activation. These observations have important implications for the role
      of the mast cell in local immune regulation.

PMID- 8757337
TI  - Endogenous nitric oxide activates prostaglandin F2 alpha production in human
      microglial cells but not in astrocytes: a study of interactions between
      eicosanoids, nitric oxide, and superoxide anion (O2-) regulatory pathways.
AB  - Secretion of the eicosanoids, nitric oxide (NO.) and superoxide anion (O2.-) was
      evaluated in human embryonic astrocytes and microglia. An inducible form of cyclo
      oxygenase (COX 2) was demonstrated in astrocytes and microglia after IL-1 beta
      plus IFN-gamma stimulation; since 1) large amounts of PGF2 alpha were released;
      2) PGF2 alpha secretion required protein synthesis and was blocked by
      indomethacin; and 3) the response was delayed and persistent. Using the same
      inducers, astrocytes, but not microglial cells, produced NO. and had an inducible
      form of nitric oxide synthase. Conversely, microglial cells were induced by IL-1
      beta and IFN-gamma to generate superoxide anions (O2.-) through an NADPH oxidase
      dependent pathway. We then investigated interactions between these different
      pathways of synthesis by inhibition experiments. The cytokine-induced production
      of PGF2 alpha in astrocytes was not affected by exposure to N-omega-monomethyl-L
      arginine, which inhibits NO. production, whereas it was reduced by 40% in
      microglia. Since microglia did not secrete any detectable NO. in their
      supernatant, intracellular production of NO. could occur in these cells that
      positively regulated PGF2 alpha production. Exposure to indomethacin, which
      prevented PGF2 alpha production in both astrocytes and microglia, resulted in a
      64% increase in cytokine-induced NO. production by astrocytes and a 70%
      inhibition of O2.- generation by stimulated microglia. Finally, superoxide
      dismutase depletion of O2.- in astrocytes and microglia had no effect on PGF2
      alpha production in these cells. These results demonstrate that there are
      important interactions between the pathways of synthesis of inflammatory
      mediators in glial cells that could unveil additional regulatory mechanisms.

PMID- 8757338
TI  - Receptors for immune complexes activate gene expression and synthesis of matrix
      proteins in cultured rat and human mesangial cells: role of TGF-beta.
AB  - Most human glomerulonephritis are induced by the deposition and/or formation of
      immune complexes in the glomerular region. Recently, it has been demonstrated
      that cultured glomerular mesangial cells (MC) express Fc receptors for IgA and
      IgG (Fc-alpha and Fc-gamma receptors). In this work, we studied whether the
      interaction of IgA and IgG complexes with MC induces accumulation of mesangial
      matrix, the histologic hallmark of progressive glomerular diseases. The exposure
      of MC to IgA and IgG complexes increased extracellular matrix components, such as
      fibronectin (FN) and collagens, at both the mRNA and protein levels in a time-
      and dose-dependent manner. Monomeric IgA or F(ab')2 fragments did not increase FN
      production, indicating that a constant region of IgA and cross-linking of Fc
      alpha receptors are required. We also explored the role of TGF-beta, a
      profibrogenic cytokine, in the regulation of matrix synthesis. Both IgA and IgG
      complexes caused in MC an augmentation in TGF-beta1 mRNA and TGF-beta activity
      and the conversion of latent TGF-beta to the biologically active form. The
      coincubation of cells with complexes and a neutralizing Ab to TGF-beta
      significantly reduced the FN synthesis. These results indicate that the Fc
      receptor occupancy of MC increases the production of extracellular matrix
      proteins. The autocrine TGF-beta synthesis appears to be largely responsible for
      this effect. These findings could have implications for a better understanding of
      the glomerulosclerosis process in immune complex nephritis.

PMID- 8757339
TI  - Beta-chemokine TCA3 binds to and activates rat vascular smooth muscle cells.
AB  - The present study compares the activity of TCA3 with other beta-chemokines
      (macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and monocyte
      chemoattractant protein (MCP)-1) on rat vascular smooth muscle cells. TCA3, MIP-1
      alpha, and MCP-1 (but not MIP-1 beta) treatment stimulates chemotaxis of vascular
      smooth muscle cells. TCA3-mediated chemotactic responses are sensitive to
      treatment with pertussis toxin, suggesting that G alpha-i proteins are involved
      in TCA3 signaling of smooth muscle. In addition, TCA3, MIP-1 alpha, and MCP-1
      increase vascular smooth muscle cell adhesiveness to type III collagen. In
      contrast, stimulation with TCA3, but not other beta-chemokines, induces
      proliferation of vascular smooth muscle cells. TCA3 receptors were identified on
      rat vascular smooth muscle cells by direct binding of radiolabeled ligand. TCA3
      binds to this receptor with high affinity (3 nM). Rat vascular smooth muscle
      cells display approximately 75,000 binding sites/cell. Competitive inhibition
      studies indicated that murine MIP-1 alpha, murine MCP-1, and human RANTES are
      weak partial competitors of TCA3 binding, demonstrating the existence of a unique
      receptor for TCA3. Murine MIP-1 beta, which fails to stimulate any biologic
      functions in vascular smooth muscle cells, also does not inhibit TCA3 binding.
      The combined data demonstrate that TCA3 and other beta-chemokines can modulate
      vascular smooth muscle cell function.

PMID- 8757340
TI  - Activation of human monocytes and the acute monocytic leukemia cell line (THP-1)
      by lipoxins involves unique signaling pathways for lipoxin A4 versus lipoxin B4:
      evidence for differential Ca2+ mobilization.
AB  - Lipoxins are bioactive eicosanoids that are generated during multicellular events
      such as inflammation, thrombosis, and atherosclerosis. They have selective
      actions on peripheral blood cells, in that previous results indicate that lipoxin
      A4 (LXA4) and lipoxin B4 (LXB4) inhibit neutrophil migration while they are both
      potent stimuli of peripheral blood monocyte (PBM) chemotaxis and adherence. Here,
      we report the impact of lipoxins on levels of free cytosolic calcium ([Ca2+]i) in
      PBM and THP-1 cells (acute monocytic leukemia cells) as well as on the functional
      responses of these cells. LXA4, but not LXB4, induced a concentration-dependent
      increase in [Ca2+]i in monocytes that was half-maximal at approximately 200 nM.
      Prior exposure of the cells to EGTA reduced the LXA4-induced increase in [Ca2+]i
      by approximately 50 to 60%, indicating the contribution of both intracellular
      mobilization and external influx in LXA4 Ca2+ regulation. A leukotriene B4
      receptor antagonist, ONO 4057, did not significantly alter LXA4-induced [Ca2+]i,
      while it inhibited the action of leukotriene B4. LXA4 also induced a rise in
      [Ca2+]i in the monocytic leukemia cell line (time to reach maximum = 15.1 +/-
      0.87 s), and both LXA4 and LXB4 stimulated a concentration-dependent THP-1 cell
      adherence to laminin with concentrations as low as 10(-10)M. In contrast to the
      findings with LXA4, exposure of THP-1 or PBM to LXB4 was not accompanied by
      mobilization of intracellular Ca2+. Although both LXA4 and LXB4 stimulate
      adherence of PBM, they did not evoke superoxide anion generation by these cells,
      nor did they affect the rate of acidification of extracellular medium by
      monocytes, as monitored using a microphysiometer. Together, these results
      indicate that an increase in [Ca2+]i is a component of the signal transduction
      events following monocyte interaction with LXA4, but not LXB4, and that both LXA4
      and LXB4 are potent and selective agonists for THP-1 cells and PBM. Moreover,
      they suggest that LX display a unique profile of actions with mononuclear cells
      compared with other known agonists of monocytes, and that LX can direct monocyte
      mediated events.

PMID- 8757341
TI  - TNF receptors in murine Candida albicans infection: evidence for an important
      role of TNF receptor p55 in antifungal defense.
AB  - TNF mediates multiple biologic activities through two distinct cell surface
      receptors, TNFR-p55 and TNFR-p75. TNF plays an important role in nonspecific
      resistance against the fungus Candida albicans. We used transgenic mice deficient
      for TNFR-p55 or TNFR-p75 to investigate the role of the TNFR in antifungal
      defense. Mice deficient for TNFR-p55 have highly impaired ability to clear
      infection with C. albicans and readily succumb to the infection. Also mice
      deficient for TNFR-p75 had a significant reduction in their ability to clear the
      fungus although lethality was not increased. These data demonstrate that TNFR-p55
      in particular, but also TNFR-p75, plays a definite role in defense against
      infection with C. albicans. In NMRI mice, infection with C. albicans resulted in
      a significant systemic release of soluble (s)TNFR-p75. Cyclophosphamide-induced
      granulocytopenia led to a reduction of sTNFR-p75 release, whereas levels of
      bioactive TNF in response to fungal infection were increased. Release of sTNFR
      p55 was not affected by induction of granulocytopenia. These observations suggest
      that granulocytes are a source of sTNFR-p75, possibly contributing to regulation
      of TNF activity during infection with C. albicans.

PMID- 8757342
TI  - Altered T cell ligands derived from a major house dust mite allergen enhance IFN
      gamma but not IL-4 production by human CD4+ T cells.
AB  - Changes in the affinity of the interaction between T cell Ag receptors and their
      ligands can modulate selected T cell effector functions. Since both allergen
      specific Th2 and Th0 cells are present in the peripheral CD4+ T cell pool of
      atopic individuals, the potential to inhibit cytokine production by Th2 cells and
      promote Th1-type cytokines from Th0 cells may contribute to the down-regulation
      of allergic inflammation. The aim of this study was to investigate the effects of
      peptide analogues of a dominant T cell epitope of the group II allergen derived
      from house dust mite, residues 28 to 40, on proliferation and cytokine production
      by human Th2 and Th0 cells. From both functional competition and proliferation
      assays, using analogues substituted with alanine or charged amino acids, the
      influence of different positions in p28-40 on TCR recognition and/or MHC class II
      binding was determined. For the specific Th0 cells, generally those analogues
      that lead to a reduction in proliferation also decreased both IL-4 and IFN-gamma
      production. However, the p28-40 analogues with alanine residues at positions 34
      and 36 altered the IFN-gamma:IL-4 ratio by selectively enhancing IFN-gamma
      secretion. In the case of Th2 cells, stimulation with the peptide analogues
      induced different patterns of effector function. Selected analogues were capable
      of inducing IL-4 production in the absence of proliferation, whereas in response
      to other peptide variants of p28-40, both IL-4 production and proliferation were
      inhibited.

PMID- 8757343
TI  - HIV-1 gp120-specific antibody-dependent cell-mediated cytotoxicity correlates
      with rate of disease progression.
AB  - The Ab-dependent cell-mediated cytotoxicity (ADCC) activity of anti-gp120 Abs in
      serum from four groups of HIV-1-positive individuals in the Multicenter AIDS
      Cohort Study was evaluated at several time points over a 10-yr period. HIV-1
      positive individuals who progressed to AIDS within 3 yr of seroconversion (rapid
      progressors) were compared with seroconverters who did not progress to AIDS
      within 6 yr (nonrapid progressors) and individuals who were seropositive when
      they entered the study and did not progress to AIDS within 9-10 yr
      (nonprogressors). At the visit closest to AIDS, rapid progressors had
      significantly lower titers of Abs that mediate ADCC against HIV-1 gp120 than
      those of nonrapid progressors at corresponding visits or those of nonprogressors
      at any visit. Nonprogressors generally had high titers of ADCC Abs at all visits.
      Differences between ADCC titers of rapid progressors and nonrapid progressors or
      nonprogressors remained when longitudinal changes within individuals were
      compared. Among seroconverters who were nonrapid progressors, those with low or
      declining ADCC titers lost significantly more CD4+ cells during the study than
      those whose ADCC titers were stable or increasing, even though both groups had
      similar serum virion RNA levels. This demonstrates that high titers of Abs that
      mediate ADCC correlate with a successful host defense against AIDS.

PMID- 8757344
TI  - Hapten-induced model of murine inflammatory bowel disease: mucosa immune
      responses and protection by tolerance.
AB  - We report here a murine model for experimental chronic colitis where
      administration of trinitrobenzene sulfonic acid (TNBS) in 50% ethanol induced
      inflammation of large intestine in susceptible (C3H/HeJ and BALB/c) but not
      resistant (C57BL/6 and DBA/2) mouse strains. We queried whether mucosal
      trinitrophenyl (TNP)-specific B cell responses were induced in mice with TNBS
      induced colitis, and if induction of tolerance to TNBS by oral administration of
      this hapten protected mice from development of colitis. Isotypes and subclasses
      of polyclonal and TNP-specific Ab-forming cells (AFC) were assessed in mucosal
      and peripheral lymphoid tissues of C3H/HeJ mice with TNBS-induced colitis.
      Increased numbers of IgA- and IgG-secreting cells were found in the inflamed
      colon lamina propria. Inflamed colonic tissue also contained high frequencies of
      IgG anti-TNP AFC (predominantly of IgG1, IgG2a, and IgG2b subclasses); however,
      anti-TNP responses in noninflamed mucosal tissues of mice with colitis exhibited
      dominant IgA and IgM with low IgG anti-TNP responses. CD4+ T cells stimulated
      with TNP-splenocytes produced more IFN-gamma and less IL-4, suggesting a Th1-type
      response. Oral administration of TNBS before induction of colitis markedly
      decreased mucosal anti-TNP responses and completely inhibited anti-TNP IgG2a and
      IgG2b responses. Control mice did not show inhibition of anti-TNP AFC responses
      or TNBS-induced colitis. Intracolonic sensitization of susceptible C3H/HeJ mice
      with TNBS induces a localized IgG anti-TNP B cell response in the inflamed
      tissue, whereas prior oral administration of TNBS results in unresponsiveness to
      this agent and protects mice from development of TNBS-induced colitis.

PMID- 8757345
TI  - Genetic analysis of susceptibility to experimental autoimmune encephalomyelitis
      in a cross between SJL/J and B10.S mice.
AB  - Experimental autoimmune encephalomyelitis (EAE), a model for human multiple
      sclerosis, is a T cell-mediated autoimmune disease that can be induced in
      experimental animals by immunization with myelin Ags. Inbred strains of mice show
      varying degrees of susceptibility to EAE, indicating that susceptibility is an
      inherited trait. To define the genetic factors that control susceptibility to
      EAE, we performed linkage analysis on the first backcross (BC1) between highly
      susceptible SJL/J mice and resistant B10.S mice, both of which are of the H-2s
      haplotype. Mice were immunized for disease with encephalitogenic myelin
      proteolipid protein peptide 139 to 151, and analysis was performed on 68
      backcross mice showing the severe disease phenotype (disease score > or = 3)and
      68 backcross mice of the resistant phenotype (no clinical or histologic signs of
      disease) using microsatellite markers covering >98% of the genome. We found the
      strongest linkage (p = 0.001) with clinical disease at two loci: one at the
      telomeric end of chromosome 2, and another near the center of chromosome 3. In
      addition, several other regions showing some evidence of linkage (p < or = 0.05)
      with clinical disease were found.

PMID- 8757346
TI  - Autoantigenic epitopes on hY5 Ro RNA are distinct from regions bound by the 60
      kDa Ro and La proteins.
AB  - We recently reported the identification in human anti-Ro serum of Abs
      specifically immunoprecipitating deproteinized hY5 RNA. In the present report, we
      characterized the epitopes recognized by anti-hY5 RNA Abs. Using deletion and
      site-directed mutagenesis of hY5 cDNA and in vitro transcribed RNAs with intact
      and 3'-shortened ends, we have defined two conformational antigenic determinants
      distinct from the regions known to bind Ro and La proteins. One of these epitopes
      (epitope A) is present in the middle portion of hY5 RNA and is dependent on the
      presence of a four-nucleotide sequence (AACC at position 58-61) that may form a
      single-stranded loop. Deleting these four nucleotides or modifying the stem
      structures proximal or distal to this loop abolishes recognition of the mutated
      RNAs by Abs. The second epitope (epitope B) requires the presence of another four
      nucleotide sequence (CUUG at position 74-77) in between the Ro and La binding
      sites. Deleting this CUUG sequence or modifying nucleotides on the 5' side of the
      stem structure below the Ro60 binding site severely compromises the interaction
      with Abs. Since Abs to deproteinized hY RNAs are restricted to anti-hY5 RNA and
      target determinants not involved in interactions with known hY5 RNA-binding
      proteins, human RohY5 particles may play a direct role in the immunization
      process, leading to the production of anti-hY5 RNA autoantibodies.

PMID- 8757347
TI  - Anti-phospholipid autoantibodies bind to apoptotic, but not viable, thymocytes in
      a beta 2-glycoprotein I-dependent manner.
AB  - Anti-phospholipid autoantibodies (aPL) are associated with a clinical syndrome of
      hypercoagulability, thrombocytopenia, and fetal loss. Several groups have shown
      that the in vitro target of many aPL is not a pure phospholipid Ag, but is either
      a complex between anionic phospholipid and the plasma protein beta2-glycoprotein
      I (beta 2GPI) or the protein beta 2GPI alone. Anionic phospholipids are normally
      absent from the extracellular surface of cell membranes but redistribute from the
      inner to the outer leaflet during apoptosis. We show that aPL bind specifically
      to apoptotic, but not viable, thymocytes, and that binding is dependent upon the
      presence of beta 2GPI. Moreover, we show that beta 2GPI binds selectively to the
      surface of apoptotic thymocytes to generate an epitope for antiphospholipid
      autoantibodies. These findings suggest that apoptotic cells may be the natural
      immunogen and/or target for aPL. Moreover, we propose that the interaction of
      circulating beta 2GPI with redistributed anionic phospholipid may itself generate
      a novel ligand by which apoptotic cells are recognized directly for phagocytic
      clearance.

PMID- 8757348
TI  - Recombinant IL-4 aggravates experimental autoimmune uveoretinitis in rats.
AB  - IL-4 is the critical regulatory cytokine that preferentially promotes a Th2 type
      of immune response. In certain models of organ-specific autoimmune diseases in
      which Th1 cells are implicated in the disease process, treatment with IL-4 has
      been shown to confer protection by deviating the immune response toward a Th2
      type. In this study, we addressed the role of IL-4 in experimental autoimmune
      uveoretinitis, a prototypic Th1-dependent disease induced in susceptible animals
      following immunization with soluble retinal Ag. Interestingly, treatment of Lewis
      rats with IL-4 exacerbated experimental autoimmune uveoretinitis, and
      simultaneous treatment with neutralizing anti-IL-4 Abs attenuated this increase
      in the severity of the disease. Ex vivo analysis of cytokines produced in
      response to the immunizing Ag showed an enhancement in the levels of IFN-gamma,
      TNF-alpha, and nitric oxide following IL-4 treatment. In vitro, IL-4 augmented
      the production of IFN-gamma by Con A-stimulated splenocytes in a dose-dependent
      manner. At low concentrations of IL-4, IFN-gamma production was enhanced, while
      at higher concentrations this production was inhibited. The specificity of the
      induction of IFN-gamma by IL-4 was confirmed by neutralizing the activity of IL-4
      with anti-IL-4. Taken together, the results herein reported demonstrate that IL-4
      can induce the production of IFN-gamma and of inflammatory cytokines under
      certain conditions, and indicate that IL-4 can exert a dose-dependent
      differential effect on the induction of immune responses and on autoimmunity.

PMID- 8757350
TI  - What is the effect of integrated health systems on subspecialties in departments
      of internal medicine?

PMID- 8757349
TI  - Pleiotropic effects of immobilized versus soluble recombinant HIV-1 Tat protein
      on CD3-mediated activation, induction of apoptosis, and HIV-1 long terminal
      repeat transactivation in purified CD4+ T lymphocytes.
AB  - CD3 mAb and HIV-1 Tat protein co-immobilized on plastic were able to induce a
      strong proliferation of resting human CD4 T cells, cultured in a serum-free
      chemically defined medium. Blocking studies performed with heparin or peptides
      containing the RGD sequence demonstrated that the heparin-binding basic domain of
      Tat plays a predominant role in CD4+ T cell activation. Moreover, the enhanced
      proliferative response of CD4+ T cells to immobilized Tat appeared to be mediated
      by alpha 5, beta 1, and alpha v subunits of surface integrin receptors. In
      contrast, soluble Tat showed a dose-dependent inhibitory activity on the
      proliferative response of resting CD4+ T cells stimulated by CD3 mAb co
      immobilized with Tat or fibronectin, but not with CD28 mAb. In transient
      transfection assays performed with an HIV-1 long terminal repeat (LTR)
      chloramphenicol acetyltransferase (CAT) plasmid CD3 mAb co-immobilized with Tat
      or fibronectin or CD28 mAb significantly stimulated CAT activity over the
      background. On the other hand, while immobilized Tat alone had no effects on LTR
      transactivation, soluble Tat was able to transactivate LTR-CAT in a dose
      dependent manner. When CD4+ T cells activated by CD3 mAb co-immobilized with Tat
      were recovered, cultured for 7 days with 25 U/ml recombinant IL-2, and given an
      additional activation signal by recross-linking CD3 mAb, a marked increase of
      apoptosis was observed with respect to cells not subjected to CD3 mAb recross
      linking. While co-immobilized Tat plus CD3 mAb did not show any significant
      effect on activation-induced cell death, high concentrations of soluble Tat
      synergized with immobilized CD3 mAb in the induction of apoptosis.

PMID- 8757351
TI  - Long-term survival of patients with Wegener's granulomatosis from the American
      College of Rheumatology Wegener's Granulomatosis Classification Criteria Cohort.
AB  - OBJECTIVE: To determine survivorship in Wegener's granulomatosis (WG) in a well
      defined multicenter cohort. METHODS: Follow-up was obtained for 77 of the 85
      patients enrolled in the 1990 American College of Rheumatology vasculitis
      classification study. RESULTS: There were 28 deaths (10 females and 18 males)
      among the 77 patients available for follow-up. Standardized mortality ratios
      (SMR) were calculated with mortality data from the general population and from
      this group of patients with WG (an SMR of 1 indicates that expected and observed
      survival are identical). Overall survivorship among patients with WG was
      substantially reduced in this cohort (SMR = 4.685 +/- 0.65; for females SMR =
      6.814 +/- 1.571; for males SMR = 3.998 +/- 0.69). CONCLUSION: The life expectancy
      of patients with WG is reduced compared with the general population.

PMID- 8757352
TI  - Evaluation of an ethics consultation service: patient and family perspective.
AB  - PURPOSE: The purpose of this study was to determine whether patients and their
      families found ethics consultations to be helpful and whether they were satisfied
      with the treatment decisions that were made in those cases where ethics
      consultation was requested. METHODS: Interviews were conducted with each patient
      (or surrogate) concerning whom an ethics consultation had been provided during a
      1-year period at Loma Linda University Medical Center, excepting those who met
      exclusion criteria. The interview was done by telephone a few weeks after
      hospital discharge. It included multiple choice and open-ended questions. A
      content analysis was done on the solicited and spontaneous comments. RESULTS:
      Eighty-six ethics consultations were provided and interviews were completed for
      56 of them (65%). Fifty-seven percent of interviewees found the ethics
      consultation to have been helpful, and only 4% found them to have been
      detrimental. Interviewees were more likely to have found the consultation helpful
      when they perceived that it had resulted in a significant change in treatment,
      and were less likely to have found it helpful when the patients were more
      seriously ill. In addition, 77% were satisfied with the treatment decisions made,
      and 11% showed some degree of dissatisfaction. CONCLUSIONS: Patients and families
      found ethics consultation provided by clinical ethicists at Loma Linda University
      Medical Center to be helpful in a majority of instances, and rarely found them
      detrimental. Based on an analysis of their comments, we believe ethics
      consultations were perceived as helpful in 7 ways: increased clinical clarity,
      increased moral or legal clarity, motivation to do what they believe is right,
      facilitation of the process of decision-making, implementation of a decision,
      interpretation of technical language, and consolation and support.

PMID- 8757353
TI  - Yield of laboratory tests for case-finding in the ambulatory general medical
      examination.
AB  - PURPOSE: To examine the diagnostic and therapeutic yield of frequently obtained
      laboratory tests for case-finding in the comprehensive ambulatory medical
      examination. PATIENTS AND METHODS: A prospective cohort study was conducted in
      four Mayo Clinic general internal medicine divisions that provide care to
      community, regional, and geographically distant patients. The main outcome
      measurements were the diagnostic yield and therapeutic yield of the complete
      blood count, chemistry panel, lipid profile, thyroid tests, and urinalysis
      ordered for case-finding. RESULTS: Overall, 1,508 laboratory tests consisting of
      7,008 individual components were obtained for case-finding in the 531 patients
      (mean age 63 +/- 14 years; 57% female). Thirty-six percent (544 of 1508) of the
      tests were abnormal, of which 6% (33 of 544) were repeated and 9% (47 of 544) led
      to further investigations. The 1,508 case-finding tests had a diagnostic yield of
      4.8% (73 new diagnoses) and a therapeutic yield of 4.0% (60 new therapies). The
      therapeutic yield of each test ordered for case-finding was as follows: lipid
      profile (16.5%), chemistry panel (2.8%), complete blood count (0.9%), urinalysis
      (0.8%), and thyroid tests (0.7%). Therapeutic yield was not associated with
      patient's age, gender, or referral distance but was approximately twice as high
      in new patients compared with established patients. CONCLUSIONS: The majority of
      treatments for conditions identified by case-finding laboratory tests resulted
      from the lipid profile. The therapeutic yield of the chemistry panel was low, and
      the therapeutic yield of the complete blood count, thyroid tests, and urinalysis
      were all less than 1%. The low therapeutic yield of many routine laboratory tests
      ordered for case-finding should be provided to patients, physicians, and managed
      care organizations to set priorities for case-finding and screening.

PMID- 8757354
TI  - Performance of alcoholism screening questionnaires in elderly veterans.
AB  - PURPOSE: To validate three alcoholism screening questionnaires in elderly male
      veterans. PATIENTS: Participants were 120 male veterans aged 65 years or older.
      METHODS: In this cross-sectional study, consecutive patients in the outpatient
      general medical practice at the Omaha VA Medical Center were interviewed with the
      alcohol module of the Revised Diagnostic Interview Schedule (DIS-III-R) and three
      alcoholism screening questionnaires, the Michigan Alcoholism Screening Test
      Geriatric Version (MAST-G), the CAGE, and the Alcohol Use Disorders
      Identification Test (AUDIT). Performance characteristics (sensitivity,
      specificity, predictive values, likelihood ratios, and areas under the receiver
      operating curve [ROC]) of the screening questionnaires were determined in
      comparison with the DIS-III-R. RESULTS: Forty-three participants (36%) met DSM
      III-R (Diagnostic and Statistical Manual of Mental Disorders) criteria for
      alcohol abuse or dependence; 23% were active drinkers and 13% were inactive.
      Fifty of the 120 (42%) reported abstinence from drinking during the preceding
      year. A MAST-G score > or = 5 had a sensitivity and specificity of 70% and 81%,
      respectively. A CAGE score > or = 2 had a sensitivity and specificity of 63% and
      82%. Using active drinkers only, an AUDIT score of > or = 8 had a sensitivity and
      specificity of 33% and 91%. The positive predictive values (PPV) for the MAST-G,
      CAGE, and AUDIT were 67%, 66%, and 69%, respectively; the negative predictive
      values were 83%, 80%, and 68%, respectively. Areas under the receiver operating
      curves for the MAST-G, CAGE, and AUDIT were 0.84 +/- 0.04, 0.77 +/- 0.05, and
      0.56 +/- 0.08, respectively. CONCLUSION: The MAST-G and the CAGE outperformed the
      AUDIT for detecting alcohol abuse and dependence in an elderly male veteran
      population. The CAGE, requiring only four easily memorized questions to achieve
      similar accuracy, appears to offer an advantage over the 24-item MAST-G.

PMID- 8757355
TI  - Plasma levels of thrombomodulin in pulmonary hypertension.
AB  - BACKGROUND: Long-standing pulmonary hypertension (PH) leads to structural
      alterations of the pulmonary vasculature and its endothelium, and occlusion of
      small vessels by microthrombi. In patients with PH, the search for factors
      inducing or worsening endothelium damage and in situ thrombi is still ongoing.
      Thrombomodulin (TM), an endothelial cell membrane protein, is a receptor for
      thrombin and a major anticoagulant proteoglycan. PURPOSE: To analyze plasma TM
      levels in patients with different forms of severe PH. PATIENTS: We prospectively
      studied 32 consecutive patients with PH referred for heart, lung, or heart-lung
      transplantation: 11 patients with primary PH (group 1), 11 patients with
      secondary precapillary PH (Eisenmenger's syndrome, group 2) and 10 patients with
      secondary postcapillary PH due to congestive heart failure (group 3). Thirty
      eight healthy subjects were also studied as a control group. METHODS: Plasma
      concentrations of TM were measured by an immunoenzymatic technique that uses two
      anti-TM monoclonal antibodies that have a strong avidity and react with different
      epitopes of the molecule. RESULTS: Thrombomodulin plasma levels decreased in all
      patients with precapillary PH, and this decrease was highly significant compared
      with controls (26 +/- 2 versus 44 +/- 2 ng/mL, P = 0.0001). In primary PH, the TM
      decrease was only significant in males whereas in the Eisenmenger's syndrome TM
      values were the lowest of all the patients studied, with mean values twice as low
      as controls (22 +/- 2 versus 44 +/- 2 ng/mL, P = 0.0001). In contrast, in
      postcapillary PH, studied only in males, TM levels were increased (85 +/- 17
      versus 54 +/- 3 ng/mL, P = 0.02). Patients with precapillary PH had more severe
      disease than patients with postcapillary PH, with higher pulmonary artery
      pressure and pulmonary vascular resistance (P < 0.001). There was no correlation
      between TM plasma levels and all hemodynamic variables. CONCLUSION: We found low
      levels of plasma TM in patients with precapillary PH but not in postcapillary PH
      compared with healthy controls. This may be related to the severity of PH and may
      contribute to the initiation or worsening of in situ thromboses frequently found
      in pulmonary hypertension. Further studies should analyze whether other markers
      of endothelial cell damage are correlated with plasma TM levels in patients with
      precapillary pulmonary hypertension.

PMID- 8757356
TI  - Mycoplasma pneumoniae pneumonia following assisted ventilation.
AB  - BACKGROUND: Mycoplasma pneumoniae pneumonia is regarded as a community-acquired
      pneumonia, rarely requiring hospitalization, with sporadic cases or limited
      outbreaks occurring after close contacts with an infected patient. Few reports
      mention M pneumoniae pneumonia acquired during hospitalization. PATIENTS AND
      METHODS: M pneumoniae was diagnosed in patients who developed pneumonia following
      perioperative and postoperative assisted ventilation by the isolation of M
      pneumoniae from bronchial washing, the detection of M pneumoniae DNA from
      bronchial washing, and serologic testing for the presence of specific
      immunoglobulin M (IgM) antibodies. RESULTS: Four patients were diagnosed as
      having M pneumoniae pneumonia following mechanical ventilation over a 1 1/2-year
      period. They were men, older than 50 years, and were hospitalized for vascular
      surgery. They developed febrile hypoxemia and intersticial pneumonia. Isolation
      of M pneumoniae and detection of M pneumoniae DNA were positive in 1 case;
      specific IgM antibodies were present in 4 cases. CONCLUSIONS: These observations
      allow the description of a new clinical entity and highlight the role of M
      pneumoniae as an agent of nosocomial infections. This diagnosis should be
      considered in any patient with precocious post-assisted ventilation febrile
      hypoxemia and diffuse interstitial pneumonia, and empiric treatment protocols may
      include M pneumoniae in their spectrum.

PMID- 8757357
TI  - Fluconazole versus amphotericin B in the treatment of hematogenous candidiasis: a
      matched cohort study.
AB  - PURPOSE: To compare the efficacy and toxicity of fluconazole and amphotericin B
      in the treatment of hematogenous candidiasis in cancer patients. PATIENTS AND
      METHODS: A matched cohort study of cancer patients with hematogenous candidiasis
      was conducted. Forty-five patients with hematogenous candidiasis who received
      fluconazole (200 to 600 mg/day) in an open-label trial at the University of Texas
      M. D. Anderson Cancer Center, Houston, Texas, between February 1990 and June 1992
      were matched to 45 patients treated with amphotericin B (0.3 to 1.2 mg/kg/day)
      for the same diagnosis. Criteria for matching included the following prognostic
      variables at the initiation of therapy: pneumonia, neutropenia (< 1,000
      cells/mm3), number of positive blood cultures before therapy, infecting Candida
      species, underlying disease, and the simplified acute physiology score. Response
      and survival at 48 hours, after 5 days of therapy, and at the end of therapy, as
      well as toxicity rates were obtained. Other post hoc analyses were performed.
      Differences in outcomes were assessed by the McNemar, the sign, and the log rank
      tests. RESULTS: Patients were similar with respect to the matching criteria, age,
      sex, status of underlying disease, use of antibiotics and growth factors,
      duration of treatment, presence and removal of central venous catheters,
      disseminated disease, and concomitant infections. Response rates at 48 hours and
      5 days were similar between the two study groups. Overall response rates at the
      end of therapy were 73% for patients treated with fluconazole and 71% for
      patients treated with amphotericin B (P = 0.78). There were no differences in
      survival rates or causes of death. Toxicity was observed in 9% of patients
      treated with fluconazole and in 67% of patients treated with amphotericin B (P <
      0.0001). Toxic effects of amphotericin B included nephrotoxicity, hypokaliemia,
      and fever and chills. CONCLUSION: Fluconazole is effective and better tolerated
      than amphotericin B for the treatment of hematogenous candidiasis in cancer
      patients.

PMID- 8757358
TI  - Comparison of once-daily versus pharmacokinetic dosing of aminoglycosides in
      elderly patients.
AB  - PURPOSE: Once-daily dosing has been suggested as an alternative method of dosing
      aminoglycosides that would reduce their toxicity while maintaining efficacy.
      There have been no studies published to date comparing once-daily dosing and
      pharmacokinetic dosing of aminoglycosides. We conducted a randomized controlled
      trial comparing the safety and effectiveness of 4 mg/kg IV once-daily dosing of
      gentamicin or tobramycin with a pharmacokinetic dosing method using an initial
      dose of 2 mg/kg IV every 12 hours. PATIENTS AND METHODS: Ninety-six patients were
      randomly assigned to either the once-daily dosing group (4 mg/kg) or the
      pharmacokinetic dosing group (initial dose of 2 mg/kg every 12 hours). In the
      once-daily dosing group, the dosing interval was extended by 12 to 24 hours to
      maintain a serum trough concentration < 1.5 mg/L regardless of the peak
      concentration. Dosing in the other group was adjusted based on the individual
      pharmacokinetic data to achieve a serum peak concentration of 6 to 10 mg/L and a
      trough concentration below 1.5 mg/L. The patients studied were predominantly
      elderly males (mean age 69 years). All patients were assessed for treatment
      efficacy and nephrotoxicity. RESULTS: There was no significant difference between
      the two groups with regard to clinical and bacteriologic efficacy. Incidence of
      nephrotoxicity was 24% in the once-daily group and 14% in the pharmacokinetic
      dosing group but the difference was not statistically significant (P = 0.13).
      Unlike previous studies, we found a correlation between high serum peak
      concentration and incidence of nephrotoxicity in the once-daily dosing group.
      Nephrotoxicity developed in six out of 10 patients (60%) with an initial serum
      peak concentration greater than 12.0 mg/L compared to two out of 24 patients
      (8.3%) with an initial peak concentration less than 12.0 mg/L (P < 0.001) in the
      once-daily group. Serum peak concentrations in the pharmacokinetic dosing group
      were not correlated with nephrotoxicity. CONCLUSIONS: Once-daily dosing and
      pharmacokinetic dosing of aminoglycosides appear to have equal efficacy and
      toxicity. However, in the elderly population, high serum peak concentrations that
      occur with once-daily aminoglycoside dosing may increase the risk of
      nephrotoxicity.

PMID- 8757359
TI  - The outcome of patients with acute myocardial infarction ineligible for
      thrombolytic therapy. Israeli Thrombolytic Survey Group.
AB  - PURPOSE: The aim of this study was to determine the proportion of patients with
      acute myocardial infarction (AMI) excluded from thrombolytic therapy on a
      national basis and to evaluate the prognosis of these patients by reasons of
      ineligibility and according to the alternative therapies that they received
      during hospitalization. PATIENTS AND METHODS: During a national survey, 1,014
      consecutive patients with AMI were hospitalized in all the 25 coronary care units
      operating in Israel. RESULTS: Three hundred and eighty-three patients (38%) were
      treated with a thrombolytic agent and included in the GUSTO study. Ineligible
      patients for GUSTO were treated: (1) without any reperfusion therapy (n = 449),
      (2) by mechanical revascularization (n = 97), or (3) given 1.5 million units of
      streptokinase (n = 85) outside of the GUSTO protocol. The inhospital and 1-year
      post-discharge mortality rates were 6% and 2% in patients included in the GUSTO
      study; 6% and 5% in those mechanically reperfused; 15% and 10% in those treated
      with thromoblysis despite ineligibility for the GUSTO trial, and 15% and 13%
      among patients not treated with any reperfusion therapy. CONCLUSIONS:
      Ineligibility for thrombolysis among patients with AMI remains high. Patients
      ineligible for thrombolysis according to the GUSTO criteria, but nevertheless
      treated with a thrombolytic agent were exposed to an increased risk.

PMID- 8757360
TI  - Clinical and socioeconomic predispositions to complicated thyrotoxicosis: a
      predictable and preventable syndrome?
AB  - PURPOSE: To identify the clinical, demographic, and hormonal features that
      characterize and place patients at greater risk for complicated thyrotoxicosis.
      PATIENTS AND METHODS: Fifty-nine patients with documented thyrotoxicosis
      complicated by cardiovascular, neuropsychiatric, gastrointestinal, or
      thermoregulatory dysfunction, were retrospectively identified among 498,000
      hospital admissions between 1979 and 1992. Clinical, demographic, and hormonal
      information were obtained from these charts, as well as from the charts of 118
      randomly selected thyrotoxic outpatients. RESULTS: Age distribution of
      complicated thyrotoxicosis patients was bimodal, with a median of 41 years. Forty
      nine percent of patients had been previously diagnosed with thyrotoxicosis, but
      most had been noncompliant with prescribed medication. Cardiovascular
      complications were among the primary causes for admission in 46% of patients,
      followed by neuropsychiatric indications in 42%, fever in 34%, and
      gastrointestinal dysfunction in 17%. Only 8% had primary involvement of > 2 organ
      systems. There was high correlation between organ systems with pre-existing
      dysfunction and those with a complication of thyrotoxicosis (P < 0.0001).
      Compared to uncomplicated controls, patients with complicated thyrotoxicosis were
      more likely to be uninsured or covered by Medicaid (OR, 2.64; 95% CI 1.78 to
      3.91); to be < 30 or > 50 years old (OR, 1.93; 95% CI 1.23 to 3.03); and to have
      serum T4 concentrations greater than twice the upper limit of normal (OR, 1.67;
      95% CI, 1.15 to 2.44). CONCLUSIONS: Certain thyrotoxic patients are at greater
      risk for developing complications. By addressing the medical needs of these
      patients, it may be possible to reduce the likelihood of complications requiring
      hospitalization.

PMID- 8757361
TI  - Antiplatelet therapy.
AB  - The major clinical indication for antiplatelet therapy has been the prevention of
      arterial thrombosis. Arterial thrombi are composed of predominantly platelets
      formed under conditions of elevated shear stress at sites of atherosclerotic
      vascular injury and disturbed blood flow. Aspirin, the prototype antiplatelet
      agent, has been in clinical use as an antithrombotic for almost a half century.
      However, clinical trials have exposed the limitations of aspirin, and there has
      been considerable recent progress in the development of more effective
      antiplatelet agents. These newer agents are rationally based on interrupting
      specific sites in the sequence of platelet activation. Inhibitors of the initial
      step of platelet adhesion remain experimental. Inhibitors of specific platelet
      agonist-receptor interactions include antithrombins, thromboxane A2 receptor
      antagonists, and adenosine diphosphate (ADP) receptor blockers including
      ticlopidine and clopidogrel. Inhibitors of arachidonic acid metabolism and
      thromboxane A2 include omega-3 fatty acids, aspirin and other nonsteroidal
      antiinflammatory drugs that inhibit cyclooxygenase, and thromboxane synthase
      inhibitors. The clinical efficacy of many of these agents may be limited by their
      actions, which are restricted to single, specific platelet receptors or metabolic
      pathways. Global interruption of the final step of platelet aggregation can be
      achieved with monoclonal antibodies and RGD (arginine-glycine-aspartic acid)
      analogs that block ligand binding to the platelet glycoprotein IIb/IIIa complex.
      Initial clinical trials with these novel agents have demonstrated superior
      efficacy in preventing reocclusion and restenosis following coronary angioplasty
      and atherectomy.

PMID- 8757362
TI  - Refocusing on history-taking skills during internal medicine training.
AB  - Recognizing that skilled history-taking is in danger of becoming a lost art, the
      American Board of Internal Medicine calls attention to the urgent need for
      internal medicine residency programs to ensure that these skills are taught and
      assessed. Although the Board's certification examination contains standardized
      items that test the physician's ability to use information from a patient's
      medical history, the written examination cannot assess the physician's ability to
      elicit that history. The Board believes that history-taking skills will become
      even more crucial as health care delivery changes, requiring more cost efficiency
      without sacrificing quality. By highlighting the skills of effective history
      taking and strategies for assessment, the Board offers specific recommendations
      for its promotion as a key element of quality patient care.

PMID- 8757363
TI  - Borderline ovarian tumors.
AB  - Borderline tumor of the ovary (BOT) is an epithelial tumor with a low rate of
      growth and a low potential to invade or metastasize. This tumor often is
      associated with a significantly better prognosis than epithelial ovarian cancer.
      Most tumors are either serous or mucinous in histology and present as early stage
      lesions. However, stage III lesions with peritoneal implants are not uncommon.
      Patients with early stage lesions have an excellent prognosis. Patients with
      higher stage lesions have a worse prognosis. Long-term follow-up of patients with
      BOT is required since the tumor can recur up to 20 years after the initial
      diagnosis. Recently, investigators have begun to identify subsets of patients
      with a worse prognosis, such as patients with aneuploid tumors. Treatment for
      early stage lesions is surgical and conservative surgery can be accomplished
      successfully in younger patients who desire to maintain fertility. Treatment for
      later stage lesions has been approached in a variety of ways. All approaches
      initially begin with maximal cytoreductive surgery. Studies suggest that early
      stage disease should be managed with surgery alone. Conflicting results on the
      usefulness of adjuvant therapy for patients with later stage disease have been
      obtained. At this time, the usefulness of adjuvant therapy for advanced disease
      remains undetermined. Further understanding of the basis of the disease and
      analysis of specific higher risk subsets might identify patients in whom adjuvant
      therapy could be tested in the setting of controlled clinical trials.

PMID- 8757364
TI  - The kindness of strangers.

PMID- 8757365
TI  - Serum ferritin concentrations in dialysis patients.

PMID- 8757366
TI  - Mucocutaneous paraneoplastic manifestations of hematologic malignancies.

PMID- 8757367
TI  - Which tests are most useful to distinguish between clonal and reactive
      thrombocytosis.

PMID- 8757368
TI  - Granulocytopenia after combined therapy with interferon and angiotensin-
      converting enzyme inhibitors: evidence for a synergistic hematologic toxicity.

PMID- 8757369
TI  - Quality of life: who can make the judgment?

PMID- 8757370
TI  - Measuring body fat.

PMID- 8757371
TI  - High prevalence of questionable medication use in congestive heart failure.

PMID- 8757372
TI  - Octreotide scintigraphy. A new method for diagnosing pancreatic tumors.

PMID- 8757373
TI  - The use of somatostatin receptor scintigraphy in the differential diagnosis of
      pancreatic duct cancers and islet cell tumors.
AB  - OBJECTIVE: In the present study, the diagnostic value of somatostatin receptor
      scintigraphy (SRS) was evaluated in the preoperative workup in patients with
      pancreatic duct cancers and islet cell tumors, as well as in the follow-up of
      these patients. METHODS: Twenty-six patients with suspected primary pancreatic
      duct cancers and 48 patients with islet cell tumors were studied. The SRS was
      performed using the radionuclide-labeled somatostatin analogue 111In-octreotide.
      Another group of 12 patients who were still alive more than 3 years after
      pancreaticoduodenectomy for pancreatic duct adenocarcinomas also underwent SRS.
      RESULTS: In 31 (65%) of 48 patients, the primary pancreatic islet cell tumor as
      well as its often previously not yet recognized metastases could be visualized.
      In contrast, none of the 26 pancreatic adenocarcinomas or their metastases could
      be seen. In 5 of 12 patients who were alive more than 3 years after
      pancreaticoduodenectomy for pancreatic duct adenocarcinomas, metastatic lesions
      were visualized at SRS. In retrospect, these patients were not operated on for
      adenocarcinomas but for "nonfunctioning" islet cell tumors. CONCLUSIONS: The
      present study supports the concept that SRS has a place in the preoperative
      differential diagnosis of islet cell tumors and pancreatic duct cancers as well
      as in the follow-up, especially in those cases in which no tumor histologic
      analysis was obtained, or the pathologic examination of the tumor tissue had not
      included special staining procedures for neuroendocrine characteristics. Our
      results also indicate that the evaluation of the results of investigations on the
      role of surgery or radiation therapy and chemotherapy or both in pancreatic duct
      cancer have to be interpreted with caution, if no histologic analysis and
      staining for neuroendocrine characteristics was performed.

PMID- 8757374
TI  - Primary aldosteronism. Results of surgical treatment.
AB  - SUMMARY BACKGROUND DATA: Management of primary hyperaldosteronism has undergone
      dramatic changes in the past 40 years. This retrospective study was carried out
      to review our recent surgical experience and to identify potential factors
      associated with postoperative persistent hypertension. METHODS: Forty-six
      patients who had adrenal surgery for primary hyperaldosteronism from 1983 to 1994
      were included in the study. RESULTS: Periodic paralysis occurred in 12 (26%)
      patients. Hypertension and hypokalemia (mean serum potassium, 2.2 + 0.5 [+
      standard deviation (SD) mmol/L) were present in all patients. Postural study was
      diagnostic in 85% (23 of 27). Computed tomography scan correctly localized the
      tumor in all except 1 patient, and venous sampling was performed in 11 patients.
      There was no operative mortality, and complications developed in six patients
      (13%), including one patient requiring re-exploration for hemostasis. All
      patients had a histologically documented adenoma. During a mean follow-up of 51
      months, 34 (77%) of the 44 patients required no further antihypertensive
      treatment. Two patients were lost to follow-up. Age, response to spironolactone
      treatment, and blood pressure on discharge were risk factors identified for
      persistent hypertension. CONCLUSION: Primary hyperaldosteronism due to
      aldosterone-producing adenoma can be diagnosed and localized expeditiously,
      whereas surgical treatment can be performed safely. Hypokalemia may be cured by
      surgical treatment, although persistent hypertension, usually of a mild degree,
      still occurs in selected patients.

PMID- 8757375
TI  - A randomized study comparing laparoscopic versus open repair of perforated peptic
      ulcer using suture or sutureless technique.
AB  - OBJECTIVE: This study compares laparoscopic versus open repair and suture versus
      sutureless repair of perforated duodenal and juxtapyloric ulcers. BACKGROUND
      DATA: The place of laparoscopic repair of perforated peptic ulcer followed by
      peritoneal toilet of the peritoneal cavity has been established. Whether repair
      of the perforated peptic ulcer by the laparoscopic approach is better than
      conventional open repair and whether sutured repair is better than sutureless
      repair are both undetermined. METHODS: One hundred three patients were randomly
      allocated to laparoscopic suture repair, laparoscopic sutureless repair, open
      suture repair, and open sutureless repair. RESULTS: Laparoscopic repair of
      perforated peptic ulcer (groups 1 and 2) took significantly longer than open
      repair (groups 3 and 4; 94.3 +/ 40.3 vs. 53.7 +/ 42.6 minutes: Student's test, p
      < 0.001), but the amount of analgesic required after laparoscopic repair was
      significantly less than in open surgery (median 1 dose vs. 3 doses) (Mann-Whitney
      U test, p = 0.03). There was no significant difference in the four groups of
      patients in terms of duration of nasogastric aspiration, duration of intravenous
      drip, total hospital stay, time to resume normal diet, visual analogue scale
      score for pain in the first 24 hours after surgery, morbidity, reoperation, and
      mortality rates. CONCLUSIONS: Laparoscopic repair of perforated peptic ulcer is a
      viable option. Sutureless repair is as safe as suture repair and it takes less
      time to perform.

PMID- 8757376
TI  - Stimulation of pancreatic growth. Distal small bowel resection mediated by
      increased levels of cholecystokinin.
AB  - SUMMARY BACKGROUND DATA: Distal, but not proximal, resection of the small bowel
      induces growth of rat pancreas, but the mechanism of this phenomenon is poorly
      clarified. The release of cholecystokinin (CCK), a trophic hormone for the
      pancreas, is regulated by a negative-feedback control of bile salts. The ileum is
      a major site for reabsorption of bile salts. Thus, unsuppressed release of CCK
      due to deleted reabsorption of bile salts after distal small bowel resection may
      be a cause of pancreatic growth. In this study, the authors have examined whether
      pancreatic growth after distal small bowel resection was mediated by endogenous
      CCK and have determined whether the mechanism of this pancreatic growth required
      biosynthesis of polyamine. METHODS: Male Fischer 344 rats underwent 70% distal
      small bowel resection or transection of the ileum. Beginning 48 hours after
      surgery, CR1409 (a CCK-receptor antagonist) or saline was injected subcutaneously
      every 8 hours. All animals were pair-fed and killed 14 days after surgery. The
      pancreas from each rat was excised, weighed, and assayed for DNA, RNA, protein,
      and polyamine content. RESULTS: Distal small bowel resection increased pancreatic
      weight, DNA, RNA, and protein, as well as polyamine levels; all of these
      increases were significantly suppressed by CR1409. Postprandial release of CCK
      into the circulation was significantly increased after distal small bowel
      resection. CONCLUSIONS: Pancreatic growth after distal small bowel resection was
      associated with the stimulation of polyamine biosynthesis; growth appeared to be
      mediated by endogenous CCK.

PMID- 8757377
TI  - An external audit of laparoscopic cholecystectomy in the steady state performed
      in medical treatment facilities of the Department of Defense.
AB  - OBJECTIVE: This study provides the first objective assessment of a complete
      patient population undergoing laparoscopic cholecystectomy in the steady state.
      The authors determined the frequency of complications, particularly bile duct,
      bowel, vascular injuries, and deaths. SUMMARY BACKGROUND DATA: This retrospective
      study, conducted for the Department of Defense healthcare system by the Civilian
      External Peer Review Program, is the second complete audit of laparoscopic
      cholecystectomy. Data were collected on 9130 patients undergoing laparoscopic
      cholecystectomy between January 1993 and May 1994. METHODS: The study sample
      consisted of clinical data abstracted from the complete records of 9054 (99.2%)
      of the 9130 laparoscopic cholecystectomies performed at 94 military medical
      treatment facilities. RESULTS: Of 10,458 cholecystectomies performed in the
      Military Health Services System, 9130 (87.3%) were laparoscopic and 1328 (12.7%)
      were traditional open procedures. Seventy-six medical records were incomplete:
      however, there was sufficient data to determine mortality and bile duct injury
      rates. Of the remaining 9054 cases, 6.09% experienced complications, including
      bile duct (0.41%), bowel (0.32%), and vascular injuries (0.10 percent). The
      mortality rate was 0.13%. Access via Veress technique was used in 57.6% and
      Hasson technique in 42.4% of patients. Intraoperative cholangiograms were
      performed in 42.7% of the cases with a success rate of 86.2%. Eight hundred
      ninety-two (9.8%) patients were converted to open cholecystectomies. CONCLUSIONS:
      In the steady state, despite an increase in the percentage of laparoscopic
      cholecystectomies performed for nonmalignant gallbladder disease, there continues
      to be minimal complications and low mortality.

PMID- 8757378
TI  - Portal triad clamping or hepatic vascular exclusion for major liver resection. A
      controlled study.
AB  - OBJECTIVE: The authors compared operative course of patients undergoing major
      liver resections under portal triad clamping (PTC) or under hepatic vascular
      exclusion (HVE). SUMMARY BACKGROUND DATA: Reduced blood loss during liver
      resection is achieved by PTC or HVE. Specific complications and postoperative
      hepatocellular injury mediated with two procedures have not been compared.
      METHODS: Fifty-two noncirrhotic patients undergoing major liver resections were
      included in a prospective randomized study comparing both the intraoperative and
      postoperative courses under PTC (n = 24) or under HVE (n = 28). RESULTS: The two
      groups were similar at entry, but eight patients were crossed over to the other
      group during resection. In the HVE group, hemodynamic intolerance occurred in
      four (14%) patients. In the PTC group, pedicular clamping was not efficient in
      four patients, including three with involvement of the cavohepatic intersection
      and one with persistent bleeding due to tricuspid insufficiency. Intraoperative
      blood losses and postoperative enzyme level reflecting hepatocellular injury were
      similar in the two groups. Mean operative duration and mean clampage duration
      were significantly increased after HVE. Postoperative abdominal collections and
      pulmonary complications were 2.5-fold higher after HVE but without statistical
      significance, whereas the mean length of postoperative hospital stay was longer
      after HVE. CONCLUSIONS: This study shows that both methods of vascular occlusion
      are equally effective in reducing blood loss in major liver resections. The HVE
      is associated with unpredictable hemodynamic intolerance, increased postoperative
      complications with a longer hospital stay, and should be restricted to lesions
      involving the cavo-hepatic intersection.

PMID- 8757379
TI  - The long-term outcome of hepaticojejunostomy in the treatment of benign bile duct
      strictures.
AB  - OBJECTIVE: The authors review the treatment and outcome of patients with benign
      bile duct strictures who underwent biliary enteric repair. SUMMARY BACKGROUND
      DATA: The authors conducted a retrospective review of all clinical records of
      patients referred for treatment of benign bile duct strictures caused by surgery,
      trauma, or common bile duct lithiasis or choledochal cyst. The authors performed
      univariate and multivariate analyses of clinical and pathologic factors in
      relation to patient outcome and survivals. METHODS: Eighty-four patients with
      documented benign bile duct strictures underwent hepaticojejunostomy,
      choledochojejunostomy, and intrahepatic cholangiojejunostomy during a 15-year
      period (January 1975 to December 1989). Morbidity, mortality, and patient
      survival rates were measured. RESULTS: Early and late outcomes correlated neither
      with demographic and clinical features at presentation nor with etiologic or
      pathologic characteristics of the stricture. Best results correlated with high
      biliary enteric anastomoses and degree of common bile duct dilatation
      independently of bile duct stricture location. CONCLUSIONS: High biliary enteric
      anastomosis provides a safe, durable, and highly effective solution to the
      problem of benign strictures of the bile duct. Transanastomotic tube stenting is
      unnecessary. Endoscopic and percutaneous transhepatic dilatation seems more
      appropriate for the treatment of patients in poor condition and those with
      anastomotic strictures.

PMID- 8757380
TI  - Assessing risk in liver transplantation. Special reference to the significance of
      a positive cytotoxic crossmatch.
AB  - OBJECTIVE: The authors determined the impact of a positive cytotoxic crossmatch
      on the outcome of liver transplantation. SUMMARY BACKGROUND DATA: Liver
      allografts rarely undergo hyperacute rejection, but transplants performed across
      a positive cytotoxic crossmatch tend to follow a different clinical course, with
      higher intraoperative blood use, postoperative graft dysfunction, and, in some
      cases, graft loss. How this affects overall graft survival has not been
      determined. METHODS: The authors provide a retrospective analysis of 1520 liver
      transplants performed between November 1989 and December 1993, with a minimum
      follow-up of 1 year. All cases had a cytotoxic crossmatch using serum pretreated
      with dithiothreitol. RESULTS: There were 1390 negative crossmatch and 130
      positive crossmatch cases. There was no difference in overall graft survival,
      although early survival rates were lower in the positive crossmatch group, with
      the maximum difference at 6 months: 0.76 (95% confidence interval, 0.74-0.78) for
      a negative crossmatch versus 0.68 (95% confidence interval, 0.61-0.77) for a
      positive crossmatch. These differences become negligible by the 2-year mark.
      Using stepwise logistic regression, the authors identified seven variables
      independently associated with outcome: 1) donor age, 2) donor gender, 3) prior
      liver transplant, 4) medical urgency status, 5) ischemia time, 6) indication for
      transplantation, and 7) primary immunosuppressant. CONCLUSIONS: The cytotoxic
      crossmatch is not statistically associated with overall graft survival after
      liver transplantation. However, early failure rates are higher in the positive
      crossmatch cases, a difference that disappears by the second year.

PMID- 8757381
TI  - Cytokine and hormonal changes after cholecystectomy. Effect of ibuprofen
      pretreatment.
AB  - OBJECTIVE: Surgical stress induces hormonal and cytokine responses proportional
      to the extent of the injury. Therefore, the authors assessed the effect of
      ibuprofen pretreatment on metabolic and hormonal changes after surgery. SUMMARY
      BACKGROUND DATA: Postoperative administration of cyclo-oxygenase inhibitor
      reduces cytokine production and nitrogen losses. METHODS: The authors studied the
      plasma hormones and metabolic and cytokines changes after perioperative ibuprofen
      administration in 22 patients undergoing cholecystectomy under inhalational
      anesthesia. Suppositories containing ibuprofen (500 mg) or placebo were
      administered 12 and 2 hours before surgery, and every 8 hours until the third
      postoperative day. Blood samples were collected 24 and 2 hours before surgery and
      2, 4, 6, 24, 48, and 72 hours after surgery for glucose, C-reactive protein,
      leukocytes, adrenocorticotropic hormone (ACTH), cortisol, tumor necrosis factor,
      and interleukin-1 and interleukin-6 determinations. RESULTS: In both groups,
      plasma cortisol levels remained elevated for 3 days, whereas plasma ACTH levels
      returned to the basal level at day 1. The ACTH (p < 0.01), cortisol (p < 0.01),
      and glucose changes (p < 0.001) were smaller in the ibuprofen group and their
      duration was shorter. The interleukin-6 levels increased gradually after skin
      incision until the sixth hour and were significantly lower (p < 0.05) in the
      ibuprofen group. CONCLUSION: Ibuprofen pretreatment in perioperative course is
      able to reduce the endocrine response and cytokine release. Therefore, ibuprofen
      may be useful in decreasing the stress response in severely surgical patients.

PMID- 8757382
TI  - Expression of MAGE genes in human colorectal carcinoma.
AB  - OBJECTIVE: The human genes MAGE-1 and -3 encode tumor-specific peptide antigens,
      which are recognized by autologous cytotoxic T lymphocytes. The antigens coded by
      those genes may be useful for cancer immunotherapy. There is, however, little
      information on the expression of these genes in human colorectal carcinomas.
      METHOD: The expression of MAGE-1, -2, and -3 genes in 54 pairs of tumor and
      corresponding normal tissue specimens of the colorectum was determined by means
      of reverse transcription polymerase chain reaction. The induction of MAGE-1, -2, 
      3, and -4 gene expression in eight colorectal carcinoma cell lines also was
      examined by use of a demethylating agent, 5-Aza-2'-deoxycytidine (DAC). RESULTS:
      The expression of MAGE genes was not recognized in normal colorectal tissues at
      all. In tumor tissue specimens, the expression of MAGE-1, -2, and -3 was
      recognized in 16 (30%), 15 (28%), and 11 (20%) patients, respectively. The
      expression was seen frequently in patients with liver metastasis (p < 0.01).
      Although MAGE-1 or -3 genes were not induced by DAC, MAGE-2 or -4 genes were
      induced in three of four MAGE-2 negative cell lines or three of seven MAGE-4
      negative cell lines, respectively. CONCLUSIONS: The MAGE genes were expressed
      exclusively in tumor tissues of one third of patients with colorectal carcinoma.
      The identification of such tumor rejection antigens is considered to uncover a
      new possibility for the specific immunotherapy of colorectal carcinoma. The
      demethylating agent may increase the number of patients who might be candidates
      for MAGE-specific immunotherapy.

PMID- 8757384
TI  - A learning curve for laparoscopic fundoplication. Definable, avoidable, or a
      waste of time?
AB  - OBJECTIVE: The objective of this study was to determine whether a learning curve
      for laparoscopic fundoplication can be defined, and whether steps can be taken to
      avoid any difficulties associated with it. SUMMARY BACKGROUND DATA: Although
      early outcomes after laparoscopic fundoplication have been promising,
      complications unique to the procedure have been described. Learning curve
      problems may contribute to these difficulties. Although training recommendations
      have been published by some professional bodies, there is disagreement about what
      constitutes adequate supervised experience before the solo performance of
      laparoscopic antireflux surgery, and the true length of the learning curve.
      METHODS: The outcome of 280 laparoscopic fundoplications undertaken by 11
      surgeons during a 46-month period was assessed prospectively. The experience was
      analyzed in three different ways: 1) by an assessment of the overall learning
      experience within chronologically arranged groups, 2) by an assessment of all
      individual experiences grouped according to the experience of individual
      surgeons, and 3) by a comparison of early outcomes of operations performed by the
      surgeons who initiated laparoscopic fundoplication with the early experience of
      surgeons beginning laparoscopic fundoplication later in the overall institutional
      experience. RESULTS: The complication, reoperation, and laparoscopic to open
      conversion rates all were higher in the first 50 cases performed by the overall
      group, and in the first 20 cases performed by each individual surgeon. These
      rates were even higher in the initial first 20 cases, and the first 5 individual
      cases. However, adverse outcomes were less likely when surgeons began
      fundoplication later in the overall experience, when experienced supervision
      could be provided. CONCLUSIONS: A learning curve for laparoscopic fundoplication
      can be defined. Experienced supervision should be sought by surgeons beginning
      laparoscopic fundoplication during their first 20 procedures. This should
      minimize adverse outcomes associated with an individual's learning curve.

PMID- 8757383
TI  - Glutamine as a regulator of DNA and protein biosynthesis in human solid tumor
      cell lines.
AB  - OBJECTIVE: The transport of glutamine by six different human solid tumor-derived
      cell lines (e.g., breast, colon, liver) was characterized and the impact of
      glutamine deprivation on rates of tumor cell proliferation and DNA and protein
      synthesis was assayed. SUMMARY BACKGROUND DATA: Glutamine is added routinely to
      cell culture media and its importance for cellular growth has been established.
      However, carrier-mediated glutamine transport by solid tumors has not been
      studied extensively, and the mechanisms by which glutamine contributes to cell
      growth regulation require further investigation. METHODS: In a panel of different
      human solid tumor-derived cells, sodium-dependent glutamine transport was
      characterized in vitro and rates of cell proliferation, protein and DNA
      synthesis, as well as thymidine transport, were correlated with glutamine
      concentrations in the culture media. RESULTS: In all cells, regardless of tissue
      origin, sodium-dependent glutamine transport was mediated almost exclusively by a
      single carrier. There was a range of Michaelis constants (Km) and maximal
      transport velocities (Vmax) for the glutamine transporter in each cell type, but
      the amino acid inhibition profiles were nearly identical, consistent with uptake
      by the System ASC family of transporters. Rates of cell growth, DNA and protein
      synthesis, and thymidine transport correlated with the glutamine concentration in
      the culture media, indicating the central role of this amino acid in regulating
      cellular proliferation. CONCLUSIONS: These data indicate that glutamine transport
      by all solid tumors is mediated by the System ASC family of transporters. The
      variation in Km values suggests that some cancers may be better suited to survive
      in a low glutamine environment than others. The mechanism by which glutamine
      supports cell proliferation and regulates cell cycle kinetics involves its
      modulation of DNA and protein biosynthetic rates.

PMID- 8757386
TI  - Endotoxic shock after long-term resuscitation of hemorrhage/reperfusion injury
      decreased splanchnic blood flow and eicosanoid release.
AB  - OBJECTIVE: The authors examine the hypothesis that hemorrhage/reperfusion injury
      predisposes the splanchnic bed to decreased prostacyclin (PGl2) release and blood
      flow after subsequent endotoxin challenge. SUMMARY BACKGROUND DATA: Prostacyclin
      is a potent vasodilator that has been demonstrated to be an important regulator
      of splanchnic blood flow. Previous studies have demonstrated that during
      resuscitation from severe hemorrhage, there is a marked reduction in intestinal
      PGl2 levels, which is associated with reduced splanchnic perfusion. METHODS:
      Anesthetized Sprague-Dawley rats underwent hemorrhage to a mean arterial pressure
      of 30 mmHg for 30 minutes followed by the reinfusion of shed blood. Then the
      animals were maintained on total parenteral nutrition (TPN) for 10 days, after
      which time they received 20 mg/kg Escherichia coli endotoxin intraperitoneally.
      Aortic and superior mesenteric artery (SMA) blood flow was monitored with a
      Doppler flow probe. The splanchnic bed was excised and perfused in vitro for
      measurement of venous effluent eicosanoid concentrations. Controls consisted of
      animals that received TPN and endotoxin but did not undergo hemorrhage and
      resuscitation (sham). RESULTS: Total parenteral nutrition support of sham animals
      followed by endotoxin challenge did not alter splanchnic eicosanoid release or
      blood flow. Hemorrhage/reperfusion animals supported by long-term TPN and
      challenged with endotoxin demonstrated a threefold decrease in splanchnic
      prostacyclin metabolite (6-keto-PGF1 alpha) release and a 50% decrease in SMA
      blood flow. CONCLUSIONS: Hemorrhage/reperfusion injury predisposes the splanchnic
      bed from rats sustained with long-term TPN to decreased release of PGl2 and SMA
      blood flow when challenged with endotoxin as a second injury.

PMID- 8757385
TI  - Ileocecal reservoir reconstruction with physiologic function after total
      mesorectal cancer excision.
AB  - BACKGROUND/AIMS: After proctectomy for low rectal cancer and straight coloanal
      reconstruction, the main causes for increased daily stool frequency, urgency, and
      incontinence are the limited capacity and distensibility of the anastomosed colic
      segment in the pelvis. The authors postulated that a pedunculated (preserving the
      nerve) ileocecal interpositional graft (cecum-reservoir) placed between the
      sigmoid colon and the anal canal would greatly reduce these inconveniences.
      METHODS: The authors evaluated the safety, defecation quality, and anorectal
      physiology of such a neorectum in 20 consecutive patients with rectal carcinoma
      between 5 and 10 cm above the anal verge who underwent total mesorectal excision.
      RESULTS: No perioperative morbidity related to the technique and no mortality was
      observed in these 20 patients. Six months after the operation, 16 patients showed
      excellent and 4 patients good defecation quality, with maximal tolerable volumes,
      compliance, and mean colonic transit times comparable to age- and gender-matched
      healthy volunteers. In addition, anal resting pressure was decreased, squeeze
      pressure was maintained, and the rectoanal inhibitory reflex remained positive in
      80%. CONCLUSIONS: The cecum-reservoir as a neorectum, using an intact
      neurovascular colonic segment, is a safe technique, providing excellent
      defecation quality. It enables a nearly normal physiologic anorectal function,
      which is already seen 6 months postoperatively.

PMID- 8757387
TI  - Is postoperative radiotherapy for thymoma effective?
AB  - OBJECTIVE: The authors determined the effect of postoperative mediastinal
      irradiation in preventing local and pleural recurrence of thymoma. SUMMARY
      BACKGROUND DATA: The role of mediastinal irradiation after incomplete resection
      or biopsy of an invasive thymoma is well established. However, routine use of
      adjuvant mediastinal irradiation for patients with thymoma after complete
      resection remains controversial. METHODS: During the 19-year period from 1973 to
      1992, operations were performed on 89 patients with thymoma. Of these 89
      patients, 80 patients who underwent gross complete tumor resection including
      adjacent tissues that appeared to be invaded by tumor were selected for this
      study. The effects of postoperative mediastinal irradiation on the recurrence
      rate of thymoma were analyzed according to histologic type, clinical stage, and
      whether adhesions to or invasion of the pleura or pericardium were present.
      RESULTS: Recurrence of thymoma was observed in 13 of 80 (16.3%) patients. No
      recurrence was observed in 23 patients with noninvasive thymoma. In patients with
      invasive thymoma whose tumor was macroscopically adherent to the pleura but not
      microscopically invasive (p1), recurrence was observed in 4 of 11 patients
      (36.4%) when mediastinal irradiation was not performed, but in none of 10
      patients who received mediastinal irradiation. However, in patients with
      microscopic pleural invasion (p2), a high recurrence rate was observed with
      mediastinal irradiation (40%, 6/15 patients) or without mediastinal irradiation
      (30%, 3/10 patients). Postoperative mediastinal irradiation for patients with
      microscopical invasion to pericardium (c2) did not decrease the recurrence rate.
      Analysis of the mode of recurrence showed that mediastinal irradiation may have
      been effective in preventing local recurrence, but it did not control the pleural
      dissemination that was observed in 12 of 13 recurrent cases. CONCLUSIONS:
      Mediastinal irradiation is not necessary for patients with noninvasive thymoma.
      In patients with invasive thymoma, postoperative mediastinal irradiation is
      effective in preventing recurrence in patients with p1 thymoma, but not in
      patients with p2 or c2 tumors. Further adjuvant therapy should be performed to
      supplement mediastinal irradiation in patients with p2 or c2 thymoma, even after
      complete resection.

PMID- 8757388
TI  - Long-term outcome and quality of life after thymectomy for myasthenia gravis.
AB  - OBJECTIVE: The authors identify criteria suitable to predict long-term clinical
      improvement and evaluate quality of life after thymectomy for myasthenia. DESIGN:
      Retrospective analysis with long-term follow-up (mean 92 months) was conducted
      for 86 patients and questionnaire interviews were performed for 65 patients who
      underwent thymectomy between 1976 and 1993. MAIN OUTCOME MEASURES: The authors
      used the Osserman Score and the European Organization for Research and Treatment
      of Cancer quality-of-life questionnaire. RESULTS: After thymectomy, lasting
      benefits were achieved predominantly by patients with moderate and severe
      myasthenia, and this association was significant (p < 0.001) in both bivariable
      and multiple analyses. No correlation was observed between outcome and thymic
      pathology, patient age or gender, duration of disease, preoperative
      plasmapheresis, and medication. Restitution to normal was complete at most recent
      follow-up as to physical status, working ability, and cognitive and social
      functions, but some emotional and vegetative deficits remained. CONCLUSION:
      Future patient selection for thymectomy should-apart from those with suspected
      thymoma-concentrate on patients with moderate and severe myasthenia unresponsive
      to conservative management.

PMID- 8757389
TI  - Laparoscopic antegrade spinchterotomy for the management of complex
      choledocholithiasis.

PMID- 8757390
TI  - Association between shorter length of stay (LOS) and readmission for complication
      exists.

PMID- 8757391
TI  - Umbilical entry as an alternative in laparoscopy.

PMID- 8757392
TI  - The transcriptional regulator CPRF1: expression analysis and gene structure.
AB  - Many eukaryotic DNA-binding proteins share a conserved amino acid sequence known
      as the basic region leucine zipper (bZIP) domain. bZIP proteins recognise DNA,
      upon dimerization, in a sequence-specific manner. The Common Plant Regulatory
      Factor 1 (CPRF1) is a bZIP transcription factor from parsley (Petroselinum
      crispum), which recognises defined elements containing ACGT cores. CPRF1 genomic
      DNA was cloned and the gene was sequenced. Analysis of the sequence data revealed
      the existence of 12 exons and 11 introns within a stretch of about 9 kb. A second
      RNA species hybridising to CPRF1 probes was identified as an alternatively
      spliced, additional CPRF1 transcript containing intron 8. This polyadenylated RNA
      species showed accumulation characteristics very similar to those of the CPRF1
      mRNA. CPRF1 specifically binds an ACGT-containing element which is located within
      the composite regulatory unit that is necessary and sufficient for light
      activation of the parsley chalcone synthase (CHS) minimal promoter. Expression
      studies at the mRNA level demonstrated that CPRF1 mRNA is present in all organs
      of light-grown plants in which CHS mRNA expression is detectable, and light
      dependent CHS mRNA accumulation was shown to be blocked by cycloheximide.
      Therefore, translation of a protein factor, possibly CPRF1, may be a prerequisite
      for CHS promoter activation.

PMID- 8757393
TI  - Interactions among the bHLH domains of the proteins encoded by the Enhancer of
      split and achaete-scute gene complexes of Drosophila.
AB  - The Enhancer of split and achaete-scute gene complexes [E(spl)-C and AS-C] encode
      helix-loop-helix proteins required for neurogenesis in Drosophila. Using a
      heterologous bacterial system, we show that (i) the bHLH domains of the proteins
      encoded by the two gene complexes differ in their ability to form homo- and/or
      heterodimers; (ii) the bHLH domains of the E(spl)-C proteins m5, m7 and m8
      interact with the bHLH domains of the Ac and Sc proteins. These bHLH domains form
      an interaction network which may represent the molecular mechanism whereby the
      competent state of the proneural cells is maintained until the terminal
      determination to neuroblast occurs. Also, the pattern of interactions of the bHLH
      domains of certain proteins encoded by the two gene complexes may explain their
      functional redundancy.

PMID- 8757394
TI  - Novel alleles of cdc13 and cdc2 isolated as suppressors of mitotic catastrophe in
      Schizosaccharomyces pombe.
AB  - Cell cycle control in the fission yeast Schizosaccharomyces pombe involves
      interplay amongst a number of regulatory molecules, including the cdc2, cdc13,
      cdc25, wee1, and mik1 gene products. Cdc2, Cdc13, and Cdc25 act as positive
      regulators of cell cycle progression at the G2/M boundary, while Wee1 and Miky1
      play a negative regulatory role. Here, we have screened for suppressors of the
      lethal premature entry into mitosis, termed mitotic catastrophe, which results
      from simultaneous loss of function of both Wee1 and Mik1. Through such a screen,
      we hoped to identify additional components of the cell cycle regulatory network,
      and/or G2/M-specific substrates of Cdc2. Although we did not identify such
      molecules, we isolated a number of alleles of both cdc2 and cdc13, including a
      novel wee allele of cdc2, cdc2-5w. Here, we characterize cdc2-5w and two alleles
      of cdc13, which have implications for the understanding of details of the
      interactions amongst Cdc2, Cdc13, and Wee1.

PMID- 8757395
TI  - NUT1, a major nitrogen regulatory gene in Magnaporthe grisea, is dispensable for
      pathogenicity.
AB  - NUT1, a gene homologous to the major nitrogen regulatory genes nit-2 of
      Neurospora crassa and areA of Aspergillus nidulans, was isolated from the rice
      blast fungus, Magnaporthe grisea. NUT1 encodes a protein of 956 amino acid
      residues and, like nit-2 and areA, has a single putative zinc finger DNA-binding
      domain. Functional equivalence of NUT1 to areA was demonstrated by introducing
      the NUT1 gene by DNA-mediated transformation into an areA loss-of-function mutant
      of A. nidulans. The introduced NUT1 gene fully complemented the areA null
      mutation, restoring to the mutant the ability to utilize a variety of nitrogen
      sources. In addition, the sensitivity of Aspergillus NUT1 transformants to
      ammonium repression of extracellular protease activity was comparable to that of
      wild-type A. nidulans. Thus, NUT1 and areA encode functionally equivalent gene
      products that activate expression of nitrogen-regulated genes. A one-step
      disruption strategy was used to generate nut1- mutants of M. grisea by
      transforming a rice-infecting strain with a disruption vector in which a gene for
      hygromycin B phosphotransferase (Hyg) replaced the zinc-finger DNA-binding motif
      of NUT1. Of 31 hygromycin B (hyg-B)-resistant transformants shown by Southern
      hybridization to contain a disrupted NUT1 gene (nut1 : : Hyg), 26 resulted from
      single-copy replacement events at the NUT1 locus. Although nut1- transformants of
      M. grisea failed to grown on a variety of nitrogen sources, glutamate, proline
      and alanine could still be utilized. This contrasts with A. nidulans where
      disruption of the zinc-finger region of areA prevents utilization of nitrogen
      sources other than ammonium and glutamine. The role of NUT1 and regulation of
      nitrogen metabolism in the disease process was evaluated by pathogenicity assays.
      The infection efficiency of nut1- transformants on susceptible rice plants was
      similar to that of the parental strain, although lesions were reduced in size.
      These studies demonstrate that the M. grisea NUT1 gene activates expression of
      nitrogen-regulated genes but is dispensable for pathogenicity.

PMID- 8757396
TI  - Preferential replication-dependent mutagenesis in the lagging DNA strand in
      Escherichia coli.
AB  - The mutation frequencies attributable to -1 frameshift or one-base substitution
      in the structural genes coding for resistance to chloramphenicol (Cm) and
      tetracycline (Tc) were followed over several cycles of DNA replication, and found
      to differ several-fold, depending on the orientation of the gene on the plasmid
      with respect to the direction of (unidirectional ColE1-type) replication. The
      mutation frequency was higher when the reporter gene was present in the plasmid
      in the same orientation as the direction of the origin, i.e., when the
      transcription template is the lagging daughter strand, than when the gene was
      inserted in the opposite orientation. This significant difference in reversion
      frequencies of genes with different polarities was demonstrated only for a brief
      period of cell growth (several cycles of replication) after induction of the
      dnaQ49 mutator, but was not observed when an increased number of replication
      cycles, was permitted, most probably due to fixation of the mutation into both
      strands. The mutated intermediate DNA which possesses a misaligned basepair in
      the Cm gene was demonstrated to be replicated into two progeny DNA molecules; one
      is the chloramphenicol-resistant (CmR) DNA synthesized from the template strand
      having the mutation and the other is the CmS DNA from the template strand without
      mutation. Our results suggest that replication-dependent mutagenesis may occur
      preferentially in the lagging strand.

PMID- 8757397
TI  - MAGGY, a retrotransposon in the genome of the rice blast fungus Magnaporthe
      grisea.
AB  - Full-length copies of a previously described repetitive DNA sequence (CH2-8) were
      isolated from the genome of the Magnaporthe grisea strain 2539. One copy of the
      complete element was sequenced and found to resemble a gypsy-like LTR
      retrotransposon. We named this element MAGGY (MAGnaporthe GYpsy-like element).
      MAGGY contains two internal ORFs putatively encoding Gag, Pol and Env-like
      proteins which are similar to peptides encoded by retroelements identified in
      other filamentous fungi. MAGGY was found to be widely distributed among M. grisea
      isolates from geographically dispersed locations and different hosts. It was
      present in high copy number in the genomes of all nine rice-pathogenic isolates
      examined. By contrast, M. grisea strains isolated from other Gramineae were found
      to possess varying copy numbers of MAGGY and in some cases the element was
      completely absent. The wide distribution of MAGGY suggests that this element
      invaded the genome of M. grisea prior to the evolution of rice-specific form(s).
      It may since have been horizontally transmitted to other sub-specific groups. One
      copy of MAGGY, corresponding to the element we sequenced, was located at
      identical locations in the genomes of geographically dispersed strains,
      suggesting that this copy of the element is a relatively ancient insertion.

PMID- 8757398
TI  - The Magnaporthe grisea DNA fingerprinting probe MGR586 contains the 3' end of an
      inverted repeat transposon.
AB  - The Magnaporthe grisea repeat (MGR) sequence MGR586 has been widely used for
      population studies of the rice blast fungus, and has enabled classification of
      the fungal population into hundreds of genetic lineages. While studying the
      distribution of MGR586 sequences in strains of M. grisea, we discovered that the
      plasmid probe pCB586 contains a significant amount of single-copy DNA. To define
      precisely the boundary of the repetitive DNA in pCB586, this plasmid and four
      cosmid clones containing MGR586 were sequenced. Only 740 bp of one end of the 2.6
      bp insert in the pCB586 plasmid was common to all clones. DNA sequence analysis
      of cosmid DNA revealed that all the cosmids contained common sequences beyond the
      cloning site in pCB586, indicating that the repetitive DNA in the fingerprinting
      clone is part of a larger element. The entire repetitive element was sequenced
      and found to resemble an inverted repeat transposon. This putative transposon is
      1.86 kb in length and has perfect terminal repeats of 42 bp, which themselves
      contain direct repeats of 16 bp. The internal region of the transposon possesses
      one open reading frame which shows similarity at the peptide level to the Pot2
      transposon from M. grisea and Fot1 from Fusarium oxysporum. Hybridization studies
      using the entire element as a probe revealed that some strains of M. grisea,
      whose DNA hybridized to the pCB586 probe, entirely lacked MGR586 transposon
      sequences.

PMID- 8757399
TI  - Protein-protein interactions in the yeast PKC1 pathway: Pkc1p interacts with a
      component of the MAP kinase cascade.
AB  - The two-hybrid system for the identification of protein-protein interactions was
      used to screen for proteins that interact in vivo with the Saccharomyces
      cerevisiae Pkc1 protein, a homolog of mammalian protein kinase C. Four positive
      clones were isolated that encoded portions of the protein kinase Mkk1, which acts
      downstream of Pkc1p in the PKC1-mediated signalling pathway. Subsequently, Pkc1p
      and the other PKC1 pathway components encoding members of a MAP kinase cascade,
      Bck1p (a MEKK), Mkk1p, Mkk2p (two functionally homologous MEKs), and Mpk1p (a MAP
      kinase), were tested pairwise for interaction in the two-hybrid assay. Pkc1p
      interacted specifically with small N-terminal deletions of Mkk1p, and no
      interaction between Pkc1p and any of the other known pathway components could be
      detected. Interaction between Pkc1p and Mkk1p, however, was found to be
      independent of Mkk1p kinase activity. Bck1p was also found to interact with Mkk1p
      and Mkk2p, and the interaction required only the predicted C-terminal catalytic
      domain of Mkk1p. Furthermore, we detected protein-protein interactions between
      two Bck1p molecules via their N-terminal regions. Finally, Mkk2p and Mpk1p also
      interacted in the two-hybrid assay. These results suggest that the members of the
      PKC1-mediated MAP kinase cascade form a complex in vivo and that Pkc1p is capable
      of directly interacting with at least one component of this pathway.

PMID- 8757400
TI  - An ABC transporter is essential for resistance to the antitumor agent mithramycin
      in the producer Streptomyces argillaceus.
AB  - Mithramycin is an antitumor antibiotic synthesized by Streptomyces argillaceus.
      This producer strain is highly resistant in vivo to mithramycin (MIC 100
      micrograms/ml) but sensitive to the related drugs chromomycin and olivomycin (MIC
      10 micrograms/ml). From a genomic library of S. argillaceus DNA two cosmid clones
      were isolated which confer a high level of resistance to mithramycin on S. albus.
      The resistance genes were mapped by subcloning to a 3.9-kb PstI-PvuII fragment.
      DNA sequence analysis of this fragment revealed one incomplete and three complete
      open reading frames. Subcloning experiments demonstrated that resistance to
      mithramycin is mediated by the genes mtrA and mtrB. The mtrA gene can potentially
      encode an ATP-binding protein of the ABC transporter superfamily, containing one
      nucleotide-binding domain and showing similarity with other ABC transporters
      involved in resistance to daunorubicin, oleandomycin and tetronasin in their
      respective producer strains. The mtrB gene codes for an integral membrane protein
      with six putative transmembrane helices. A mithramycin-sensitive mutant was
      generated in a gene replacement experiment by disrupting the mtrA gene, thus
      demonstrating that the system encoded by the mtrAB genes is essential for
      conferring resistance to mithramycin in S. argillaceus.

PMID- 8757401
TI  - Localization of nusA-suppressing amino acid substitutions in the conserved
      regions of the beta' subunit of Escherichia coli RNA polymerase.
AB  - Escherichia coli RNA polymerase is composed of four different subunits, alpha
      (present in two copies), beta, beta' and sigma. Among these, the beta'
      polypeptide shares nine conserved regions with the largest subunits of eukaryotic
      RNA polymerases, but its role is poorly understood. We isolated novel mutations
      in a plasmid-borne copy of rpoC, which encodes beta', as dominant suppressors of
      two temperature-sensitive nusA alleles. All 20 suppressors of nusA11 (single
      missense mutation) isolated had either of two specific substitutions: Lys for Glu
      402 (rpoC10) and Thr for Ala-904 (rpoC111) in the beta' subunit. In vivo and in
      vitro transcription assays revealed that the rpoC10 allele of beta' participates
      in Rho-dependent transcription termination. On the other hand, of 20 suppressors
      of nusA134 (deletion of C-terminal one-third) scattered at 18 distinct sites, 16
      were assigned to one of six conserved regions C-I. These results suggested that
      the conserved domains of the beta' subunit of E. coli RNA polymerase are involved
      in transcript termination or interaction with termination factor(s).

PMID- 8757403
TI  - Replication properties of ARS1 plasmids in Saccharomyces cerevisiae: dependence
      on the carbon source.
AB  - The replication behaviour of a number of ARS1-based plasmids was investigated on
      propagation in Saccharomyces cerevisiae grown with either glucose or galactose as
      carbon source. Growth on galactose results in reduced plasmid stability, as well
      as in reduced replication efficiency, when the entire 1.5-kb TRP1-ARS1 fragment
      is present on a plasmid. The galactose sensitivity is mediated by a 0.13-kb
      fragment harbouring part of the GAL3 promoter. This fragment exerts its effect
      when situated either 5' or 3' to the ARS core consensus at distances up to 0.9
      kb. The endogenous 2 microns plasmid remained unaffected by the choice of carbon
      source.

PMID- 8757402
TI  - Molecular cloning and analysis of the dominant flocculation gene FLO8 from
      Saccharomyces cerevisiae.
AB  - A flocculation gene was cloned from a Saccharomyces cerevisiae ATCC60715 genomic
      library, known to contain the FLO8 gene, on the basis of its ability to confer a
      flocculation phenotype on a nonflocculent strain. From a total of 11 130 clones,
      four clones sharing the several restriction fragments were isolated, suggesting
      that these were derived from the same locus. The results of integration mapping
      and disruption of the cloned gene indicated that this gene was the FLO8 gene.
      After disruption of the FLO8 gene, the strain lost its ability to flocculate. The
      DNA sequence of the FLO8 gene was determined. This gene includes a 2187-bp open
      reading frame that encodes a 729-amino acid protein. Computer analysis indicated
      that the FLO8 gene has a significant degree of homology with a S. cerevisiae
      chromosome V DNA sequence, but no homology with the FLO1 gene. The hydrophobicity
      profile of the putative FLO8 gene product did not indicate the presence of any
      significantly hydrophobic regions. Southern analysis of the FLO8 gene present in
      various yeast strains indicated that the FLO8 gene is highly conserved in yeast
      strains having a variety of flocculation phenotypes and genotypes. Northern
      analysis revealed that the level of FLO1 gene transcription is dependent on the
      rate of transcription of the FLO8 gene. These results suggest that the FLO8 gene
      mediates flocculation via transcriptional activation of the FLO1 gene.

PMID- 8757404
TI  - Genome mapping of Clostridium perfringens strains with I-CeuI shows many
      virulence genes to be plasmid-borne.
AB  - The intron-encoded endonuclease I-CeuI from Chlamydomonas eugametos was shown to
      cleave the circular chromosomes of all Clostridium perfringens strains examined
      at single sites in the rRNA operons, thereby generating ten fragments suitable
      for the rapid mapping of virulence genes by pulsed-field gel electrophoresis
      (PFGE). This method easily distinguishes between plasmid and chromosomal
      localisations, as I-CeuI only cuts chromosomal DNA. Using this approach, the
      genes for three of the four typing toxins, beta, epsilon, and tau, in addition to
      the enterotoxin and lambda-toxin genes, were shown to be plasmid-borne. In a
      minority of strains, associated with food poisoning, where the enterotoxin toxin
      gene was located on the chromosome, genes for two of the minor toxins, theta and
      mu, were missing.

PMID- 8757406
TI  - Adult leukemia and proximity-based surrogates for exposure to Pilgrim plant's
      nuclear emissions.
AB  - Possible associations between adult leukemia incidence and proximity-based
      surrogate measures of potential for exposure to radioactive emissions from the
      Pilgrim nuclear power plant in Plymouth, Massachusetts, were investigated.
      Included in this study were 105 nonchronic lymphocytic leukemia cases, diagnosed
      between 1978 and 1986 at age 13 y or older, that occurred in 22 towns near
      Pilgrim; population controls numbered 208. Residence within 4 mi (6.4 km) of
      Pilgrim during "high-emissions" years was related to case-control status
      (adjusted odds ratio [OR] = 3.88, 95% confidence interval [95% CI] = 0.81-10.64).
      A high "exposure" score (i.e., a value that accounted for downwind time) was also
      related to case-control status (OR = 3.46, 95% CI = 1.50-7.96). Some
      statistically significant dose-response trends were found. Cautious
      interpretation of associations is warranted in light of the low levels of
      reported emissions.

PMID- 8757405
TI  - Breast cancer risk and residence near industry or traffic in Nassau and Suffolk
      Counties, Long Island, New York.
AB  - A case-control interview study was used to evaluate the relationship between
      breast cancer risk and residential proximity to industrial facilities and traffic
      for pre- and postmenopausal women in Nassau and Suffolk Counties on Long Island,
      New York. A geographic information system was used to assign industry and traffic
      counts to 1-km2 grid cells (5-kM2 grid cells for traffic) and to assign potential
      exposure values to study subjects, based on 20-y residential histories. A
      significantly elevated risk of breast cancer was observed among postmenopausal
      subjects who were ever potentially exposed to chemical facilities (Nassau County
      adjusted odds ratio [OR] = 1.61, 95% confidence interval [95% CI] = 1.06-2.43;
      Suffolk County adjusted OR = 1.58, 95% CI = 0.71-3.51. This elevated risk,
      however, was not observed among premenopausal subjects. Risk increased for post
      menopausal subjects as number of chemical facilities increased from one (adjusted
      OR = 1.45, 95% CI = 0.93-2.25) to two or more (adjusted OR = 3.47, 95% CI = 1.06
      11.38). Crude and adjusted ORs for high traffic density were elevated among
      Nassau--but not Suffolk--county subjects and were not significant statistically.

PMID- 8757407
TI  - Prevalence and nature of allergy and chemical sensitivity in a general
      population.
AB  - The objectives of this study were (a) to determine the self-reported prevalence
      of allergy and chemical sensitivity in a rural population of eastern North
      Carolina, (b) to determine the type and frequency of symptoms for each condition,
      and (c) to determine the demographic groups affected. A random general telephone
      survey was conducted during the period May 14, 1993, to September 10, 1993, and
      questions about allergy and chemical sensitivity were asked. Of the 1 446
      households contacted, 1 027 (71%) individuals agreed to participate. Allergies
      were reported by 365 (35%) individuals. Thirty percent of allergic individuals
      reported that symptoms occurred once or more each week, whereas 61% reported that
      symptoms occurred, at most, once each month. Allergic symptoms that occurred
      daily were reported by 5.3% of the total population. Chemical sensitivity was
      reported by 336 (33%) individuals. Thirty-five per cent of chemically sensitive
      individuals reported symptoms at least once each week, whereas 53% reported that
      symptoms occurred once (or less) each month. Symptoms of chemical sensitivity
      that occurred daily were reported by 3.9% of the total population. Both allergy
      and chemical sensitivity were distributed widely across age, income, race, and
      educational groups. Simultaneous allergy and chemical sensitivity were reported
      by 16.9% of the population, allergy without chemical sensitivity by 16.0%,
      chemical sensitivity without allergy by 18.2%, and neither condition by 48.9%. If
      the prevalence of sensitivity to chemical irritants is, in fact, equivalent to
      that of allergy, as was found in this study, then support for the scientific
      investigation of chemical sensitivity is justified.

PMID- 8757408
TI  - Urban ectopy in the mountains: carbon monoxide exposure at high altitude.
AB  - Environmental exposure to inhaled carbon monoxide (CO) increases coronary artery
      disease risk. Sudden cardiac death, a frequent manifestation of coronary artery
      disease, is usually a result of ventricular dysrhythmia. The effect of exposure
      to CO at sea level (CO/SL) and simulated high (2.1 km) altitudes (CO/HA) on the
      incidence of cardiac ectopy in subjects with coronary artery disease was
      investigated. A double-blind crossover study was conducted, with random-order
      assignment, and each subject served as his own control. Seventeen men with
      documented coronary artery disease and stable angina pectoris performed
      cardiopulmonary exercise stress tests after random exposure to either CO or clean
      air (CA) at sea level (CA/SL) or at a simulated 2.1-km high altitude (CA/HA). The
      individual CO and HA exposure conditions were each selected to reduce the
      percentage of oxygen saturation of the subjects' arterial blood by 4%. Subjects'
      blood carboxyhemoglobin levels were increased from an average of 0.62% after
      clean-air exposure to 3.91% of saturation after CO exposure. The percentage of
      oxygen saturation in arterial blood was reduced from a baseline level of 98% to
      approximately 94% after CO/SL or CA/HA and to approximately 90% after CO/HA.
      Compared with the CA/SL (i.e., 10 premature ventricular contractions [PVCs]), the
      average incidence of exercise-induced ventricular ectopy was approximately
      doubled after all exposures (CO/SL = 18 PVCs, CA/HA = 16 PVCs, and CO/HA = 19
      PVCs), and a significant trend (p < .05) of increased ectopy with decreased
      oxygen saturation in arterial blood was observed. Yet, among subjects who were
      free from ectopy (n = 11) on CA/SL, only 2 subjects developed ectopy after CO/HA.
      No episodes of ventricular tachycardia or fibrillation occurred. The findings
      indicated that exposure to increased levels of hypoxemia, resulting from hypoxic
      and/or CO exposures, increased the susceptibility to ventricular ectopy during
      exercise in individuals with stable angina pectoris; however, this risk was
      nominal for those without ectopy.

PMID- 8757409
TI  - 1,2 Dibromo-3-chloropropane (DBCP) and ethylene dibromide (EDB) in well water in
      the Fresno/Clovis metropolitan area, California.
AB  - Ground-water contamination with the pesticides 1,2 dibromo-3-chloropropane (DBCP)
      and ethylene dibromide (EDB) affects Fresno/Clovis city in California. The
      spatial and temporal distribution of DBCP and EDB in public wells in
      Fresno/Clovis was examined, using mapping and time-series analyses of chemical
      test results, during the time periods 1979-1980 and 1992-1993. Health risks were
      estimated from mean concentrations, lifetime cancer risks were estimated, and
      monitoring and control programs were reviewed. Mean DBCP concentrations in
      selected wells declined from 0.56 ppb in 1979-1980 to 0.18 ppb in 1992-1993.
      Closure of wells and wellhead filtration caused levels to be reduced further
      (i.e., to 0.06 ppb). Mean EDB concentrations declined from 0.25 ppb to 0.15 ppb
      during the same time periods. The estimated lifetime cancer risk for DBCP was 1
      excess death per 125 000 population in 1992-1993, but this risk varied within the
      city. The risk for EDB was 1 excess death per 2.2 million. Recommendations were
      made for the modeling of pesticide movement in ground water and for
      epidemiological studies.

PMID- 8757410
TI  - Estimating exposure to volatile organic compounds from municipal water-supply
      systems: use of a better computational model.
AB  - The Southington, Connecticut, water-supply system is characterized by a
      distribution network that contains more than 1 700 pipeline segments of varying
      diameters and construction materials, more than 186 mi (299 km) of pipe, 9
      groundwater extraction wells capable of pumping more than 4 700 gal/min (0.2965
      m3/s), and 3 municipal reservoirs. Volatile organic compounds, which contaminated
      the underlying groundwater reservoir during the 1970s, contaminated the water
      supply system and exposed the town's residents to volatile organic chemicals. We
      applied a computational model to the water-supply system to characterize and
      quantify the distribution of volatile organic compounds in the pipelines, from
      which we estimated the demographic distribution of potential exposure to the
      town's residents. Based on results from modeling analyses, we concluded the
      following: (a) exposure to volatile organic compound contamination may vary
      significantly from one census block to another, even when these census blocks are
      adjacent to each other within a specified radius; (b) maximum spatial spread of
      contamination in a water-distribution system may not occur under peak demand
      conditions, and, therefore, maximum spatial distribution of the exposed
      population also may not correspond to peak demand conditions, and (c) use of the
      proposed computational model allows for a more refined and rigorous methodology
      with which to estimate census-block-level contamination for exposure assessment
      and epidemiologic investigations.

PMID- 8757411
TI  - Exposure of oncologic nurses to methotrexate in the treatment of osteosarcoma.
AB  - Methotrexate is a therapeutic agent used widely for osteosarcoma. We used an
      extremely sensitive high-performance liquid-chromatography assay to evaluate 112
      urine samples obtained from 28 hospital employees during high-dose therapy with
      methotrexate and during routine care of patients. The highest cumulative urinary
      excretion was observed when methotrexate infusions were handled in a workbench
      from which a portion of filtered air was emitted into the room. Remarkable urine
      contaminations were identified for personnel, including 1 administrative employee
      who had "stood by" for 2 h in the room where infusions were prepared. Lower
      methotrexate concentrations were detected in the urine of nurses whose exclusive
      function was to care for patients. The urine burden in oncologic nurses decreased
      after a central pharmacy unit was installed. Methotrexate was excreted in the
      sweat of patients who were under high-dose therapy, and its elimination half-life
      was 11.1 h (mean maximal concentration = 1.7 micrograms/ml [n = 51). The maximal
      burden in spontaneous vomit from these patients was 441.5 micrograms/ml, and it
      declined to 0.24 micrograms/ml 19.5 h after infusion was completed. No
      methotrexate was detected in personnel who prepared 20-g methotrexate infusions
      in the central pharmacy unit. We demonstrated that occupational safety depended
      not only on technical precautions, but on the skills of specifically trained
      personnel.

PMID- 8757412
TI  - The South Karelia Air Pollution Study: effects of low-level exposure to
      malodorous sulfur compounds on symptoms.
AB  - Exposure to very low levels of ambient-air malodorous sulfur compounds and their
      effect on eye irritation, respiratory-tract symptoms, and central nervous system
      symptoms in adults were assessed. A cross-sectional self-administered
      questionnaire (response rate = 77%) was distributed during March and April 1992
      to adults (n = 336) who lived in a neighborhood that contained a pulp mill and in
      a nonpolluted reference community (n = 380). In the exposed community, the
      measured annual mean concentrations of total reduced sulfur compounds and sulfur
      dioxide measured in two stations were 2 to 3 micrograms/m3 and 1 micrograms/m3,
      respectively. In the reference community, the annual mean concentration of sulfur
      dioxide was 1 micrograms/m3. The residents of the community near the pulp mill
      reported an excess of cough, respiratory infections, and headache during the
      previous 4 wk, as well as during the preceding 12 mo. The relative risk for
      headache was increased significantly in the exposed community, compared with the
      reference area: the adjusted odds ratio (aOR) was 1.83 (95% confidence interval
      [95% CI] = 1.06-3.15] during the previous 4 wk and 1.70 (95% CI = 1.05-2.73)
      during the preceding 12 mo. The relative risk for cough was also increased during
      the preceding 12 mo (aOR = 1.64, 95% CI = 1.01-2.64). These results indicated
      that adverse health effects of malodorous sulfur compounds occur at lower
      concentrations than reported previously.

PMID- 8757413
TI  - Absence of tubular proteinuria following environmental exposure to chromium.
AB  - Certain chromium compounds are known to be nephrotoxic, but renal damage from
      long-term environmental or occupational exposure to chromium has not been
      documented. To detect possible preclinical renal damage, we tested the urine of
      55 lifelong residents of an area contaminated with chromium landfill. The levels
      of four proteins were determined in urine samples: (1) human intestinal alkaline
      phosphatase, (2) tissue nonspecific alkaline phosphatase, (3) N-acetyl-beta-D
      glucosaminidase, and (4) microalbumin. No elevated levels of proteins were found,
      and there were no significant correlations between urine protein and urine
      chromium concentrations. We concluded that long-term environmental exposure to
      chromium dust did not lead to tubular proteinuria.

PMID- 8757414
TI  - Relationship of blood lead levels to blood pressure in battery workers.
AB  - The effect of lead exposure on blood pressure in the modern industrial setting is
      controversial. In this study, we followed 67 workers in a lead-battery plant for
      6-10 y, and blood pressure and blood lead levels were measured every 6 mo.
      Weight, height, alcohol intake, cigarette smoking, and age were recorded. Partial
      correlation coefficients showed that initial systolic blood pressure, age, and
      body mass index (i.e., weight/height squared) accounted for 25%, 30.9%, and
      20.2%, respectively, of the variance in systolic blood pressure (p < .001 in all
      cases). Conversely, average blood lead levels (13 +/- 3 tests/worker) accounted
      for only 0.4% of the variance (not significant). Repeated-measures analysis of
      variance showed a small--but significant--association between blood lead levels
      and systolic blood pressure. There was a negative correlation between blood lead
      levels and diastolic blood pressure. There were 18 men with average blood lead
      levels that were less than 30 micrograms/dl (average = 25 +/- 3 micrograms/dl),
      and 32 men had levels of 40 micrograms/dl or more (average = 47 +/- 6
      micrograms/dl). The mean final systolic blood pressure, adjusted for age, and
      initial systolic blood pressure were 117 +/- 13 mm Hg and 114 +/- 11 mm Hg,
      respectively. We concluded that blood lead levels had no clinically significant
      effect on blood pressure in lead-battery workers. The main predictors of the
      follow-up systolic blood pressure were age, body mass index, and initial systolic
      blood-pressure measurements.

PMID- 8757417
TI  - Mercury vapor in amalgam waste discharged from dental office vacuum units.
AB  - Clinical procedures in dental offices generate quantities of waste slurry or fine
      particulate matter, much of which is derived from dental amalgam filling
      material. This mercury-containing material is discharged into waste streams via
      the dental office vacuum-pump system. This system also discharges large
      quantities of air, either into the atmosphere exterior to the office building or
      into the sewer system, depending on the type of equipment used. The purpose of
      this study was to investigate whether the discharged air contained mercury vapor.

PMID- 8757415
TI  - Adjustment of creatinine-adjusted value to urine flow rate in lead workers.
AB  - Two male lead workers, aged 57 and 51 y, were studied to compare the urinary
      flow/creatinine-adjusted values published earlier by Araki et al. and by
      Greenberg and Levine. We collected 24-h urine samples once a month for 31 mo and
      16 mo for workers 1 and 2, respectively. The workers' urinary excretions of lead,
      delta-aminolevulinic acid, and coproporphyrin were measured. No significant
      correlations between urine flow rate and urinary flow/creatinine-adjusted values
      published by Araki et al. for the three substances were found for these two
      workers. However, urinary flow/creatinine-adjusted values presented by Greenberg
      and Levine for lead and delta-aminolevulinic acid were correlated positively with
      urine flow rate in the two workers, and their adjusted value for coproporphyrin
      was correlated positively with urine flow rate in one of the workers. We
      concluded that use of the urinary flow/creatinine-adjusted value by Greenberg and
      Levine for biological monitoring poses a problem because of the theoretical
      fallacy.

PMID- 8757418
TI  - Letter to World Health Organization, International Labor Office, United Nations
      Environment Program, and International Program on Chemical Safety.

PMID- 8757419
TI  - Mycobacterium avium and purified protein derivative-specific cytotoxicity
      mediated by CD4+ lymphocytes from healthy HIV-seropositive and-seronegative
      individuals.
AB  - HIV is the greatest single risk factor for the development of tuberculosis.
      Diseases caused by M. tuberculosis and mycobacteria are the most common
      opportunistic infections in HIV-infected persons, which may stem from a
      functional defect of the CD4+ T-cell-mediated killing of macrophages harboring
      mycobacteria. Our objective was to investigate the M.tuberculosis-and M. avium
      specific cytotoxic capacity of T cells from healthy, bacille Calmette-Guerin
      vaccinated, HIV-seropositive individuals. Blood mononuclear cells were obtained
      from 10 healthy HIV-seropositive and 10 healthy seronegative persons with no
      history of previous or active mycobacterial infection. Antigen-specific killing
      of macrophages presenting mycobacterial antigens (purified protein derivative or
      M. avium culture filtrate) was conducted. The phenotype of the killer cells was
      determined by a fluorescence-activated cell sorter after antigen stimulation and
      by using purified CD4+ and CD8+ cell subsets. Substantial, but reduced antigen
      specific cytotoxicity was observed in patients with asymptomatic HIV infection.
      The immunological dysfunction leading to reduced cytotoxic activity in healthy
      HIV-seropositive subjects could not be explained by a defect in the cytotoxic
      capacity of the individual CD4+ lymphocyte after antigen stimulation, and it
      could not be explained by a reduction in the total number of CD4+ cells before
      antigen stimulation. The antigen-specific cytotoxic activity was, however,
      closely related to the ability of the CD4+ T cells to respond to mycobacterial
      antigens. The immunological dysfunction leading to reduced mycobacterial-specific
      cytotoxic activity in healthy HIV-seropositive subjects is caused either by a
      reduction in the number of antigen-responsive CD4+ T cells (memory) or by an
      impairment of their ability to respond to antigenic stimuli.

PMID- 8757420
TI  - The immunosuppressive peptide of HIV-1 inhibits T and B lymphocyte stimulation.
AB  - The transmembrane glycoproteins of all retroviruses contain a conserved region
      composed of a leucine zipper, an immunosuppressive domain, and an immunodominant
      Cys-Cys loop. The amino acid sequence of the immunosuppressive domain of gp41 of
      human immunodeficiency virus type 1 (HIV-1; amino acids 583-599) is closely
      related, but not identical, to the immunosuppressive domains of type C and D
      retroviruses. A synthetic peptide corresponding to the immunosuppressive domain
      of HIV-1 (immunosuppressive peptide, ISU-peptide) inhibits mitogen and lymphokine
      stimulation of T lymphocytes. It is interspecies reactive and inhibits both human
      and mouse lymphocytes. The inhibitory effect is not based on direct cytotoxicity
      and the peptide is immunosuppressive only when conjugated to a carrier protein.
      The ISU-peptide of HIV-1 also inhibits B lymphocyte stimulation by the B cell
      mitogen lipopolysaccharide and by specific antibodies against delta and mu chains
      of cell surface immunoglobulins. These data suggest that the immunosuppressive
      domain of gp41 may play an important role in the immunopathogenesis of AIDS.

PMID- 8757421
TI  - Antiviral efficacy and toxicity of ribavirin in murine acquired immunodeficiency
      syndrome model.
AB  - The antiretroviral efficacy and hematotoxicity of ribavirin, a guanosine
      analogue, have been evaluated in mice infected with the LP-BM5 virus pool [murine
      acquired immunodeficiency syndrome (MAIDS) model]. Doses ranging from 6.25 to 200
      mg/kg/day were injected intraperitoneally twice a day for 6 weeks to infected
      mice. Drug treatment induced a significant protection against splenomegaly and
      lymphadenopathy at doses > or = 25 mg/kg. Moreover, doses starting at 50 mg/kg
      protected against hypergammaglobulinemia, minimized the loss of spleen CD8+ T
      cells, and reconstituted the capacity of splenocytes to proliferate in response
      to concanavalin A. The spleen and cervical lymph node architectures were
      protected, and a reduction in the emergence of germinal centers was observed at
      50 mg/kg ribavirin. Hematotoxicity appeared at doses > or = 50 mg/kg ribavirin,
      and severe anemia was predominant only at doses of 100 and 200 mg/kg. This study
      shows that ribavirin protects mice against the effects resulting from retrovirus
      infection at doses of > or = 50 mg/kg in a MAIDS model and induces severe
      hematotoxicity at doses > or = 100 mg/kg.

PMID- 8757422
TI  - A randomized trial (ISS 901) of switching to didanosine versus continued
      zidovudine after the diagnosis of AIDS.
AB  - Although the efficacy of switching from zidovudine (AZT) to didanosine (ddI) has
      already been evaluated in controlled studies, prior investigations were not
      specifically designed to evaluate this issue in patients with acquired immune
      deficiency syndrome (AIDS). This open, randomized, multicenter study (ISS 901)
      was designed to evaluate the clinical benefit in patients with AIDS of switching
      to ddI after 6-18 months of AZT and no major intolerance. Patients were
      randomized to continue AZT, maintaining the current dosage at randomization (n =
      79), or to receive ddI (n = 80) at the dosage of 375 mg and 250 mg b.i.d. for
      body weight > 60 and < or = 60 kg, respectively. Primary efficacy measures were
      survival and time to new AIDS-defining events, analyzed by the intent-to-treat
      approach. The two groups were comparable for baseline characteristics, follow-up
      (15 months), and time spent on allocated treatment. At the end of the study, 104
      patients (48 AZT, 56 ddI) had died and 90 had at least one new AIDS-defining
      event (44 AZT, 46 ddI). Kaplan-Meier estimates of survival and of time to first
      new AIDS-defining event showed no differences between the treatment groups. No
      differences were detected in other efficacy measurements (p24 antigenemia, CD4+
      count, Karnofsky score, and body weight), occurrence of severe toxicities, and
      treatment modifications. Pancreatitis occurred only in ddI-treated patients (6%).
      In our population of patients with advanced disease, switching from AZT to ddI
      did not produce apparent benefits, suggesting that application of this strategy
      earlier in the course of human immunodeficiency virus disease should be
      considered.

PMID- 8757423
TI  - Prophylaxis with nystatin pastilles for HIV-associated oral candidiasis.
AB  - To determine whether daily use of nystatin pastilles can prevent initial outbreak
      or recurrence of oral candidiasis in HIV-infected patients and to identify
      factors associated with outbreaks during 20-week follow-up, a randomized, double
      blind, placebo-controlled clinical trial was conducted. Subjects were 128 HIV
      infected men (aged 27-60 years) who either had had no documented episode of oral
      candidiasis in the previous year or had been clinically clear of oral candidiasis
      for at least 72 h before randomization. Study arms were two placebo pastilles,
      one nystatin (200,000 U) and one placebo pastille, or two nystatin pastilles
      daily for 20 weeks. The main outcome measure was time to oral candidiasis, as
      determined by potassium hydroxide (KOH) smear and fungal culture. A multivariate
      proportional hazards model showed that four factors were significant (p < 0.001)
      in predicting time to oral candidiasis: nystatin treatment (hazard ratio 0.59),
      history of oral candidiasis (3.58), Candida albicans carriage (2.79), and CD4
      count at randomization (0.65). In this small group of subjects, nystatin appeared
      to be effective in delaying onset of oral candidiasis. Patients with CD4 counts <
      200 who are carriers of C. albicans and have a history of oral candidiasis may be
      most likely to benefit from antifungal prophylaxis.

PMID- 8757424
TI  - Dapsone- and primaquine-induced methemoglobinemia in HIV-infected individuals.
AB  - Clinically significant methemoglobinemia can develop as a result of medications.
      Although dapsone and primaquine are known to produce methemoglobinemia in
      susceptible individuals, methemoglobinemia has been reported only rarely in the
      human immunodeficiency virus (HIV) population. We describe five cases of
      methemoglobinemia caused by either primaquine or dapsone alone or in combination.
      The initial methemoglobin level ranged from 15.3% in the patient whose
      methemoglobinemia was caused by primaquine alone to 33.1%. Five patients
      developed symptomatic methemoglobinemia requiring hospitalization for 1 to 12
      days. Two cases resulted from intentional overdoses of dapsone, and three
      developed within several days of commencing primaquine while dapsone remained
      present in the bloodstream. The four severe cases required intravenous methylene
      blue, supplemental oxygen, plus erythrocyte transfusions, whereas the mild case
      responded to oxygen therapy plus discontinuation of the precipitating drugs.
      Blood gases and pulse oximetry do not aid in the diagnosis, which requires
      cooximetry. Our study indicates that dapsone and primaquine alone or in
      combination can produce clinically significant methemoglobinemia in HIV-infected
      individuals, either in the setting of an overdose or when primaquine is
      instituted before dapsone has been cleared from the bloodstream.

PMID- 8757425
TI  - Predictive value for survival of soluble tumor necrosis factor receptors p55 and
      p75 during zidovudine-containing treatment in symptomatic human immunodeficiency
      virus type 1 infection.
AB  - Previous studies of asymptomatic human immunodeficiency virus (HIV) infection
      have shown that serum levels of soluble tumor necrosis factor receptors (sTNFR)
      are good predictors of disease progression and clinical outcome during zidovudine
      (ZDV) therapy. The present study of symptomatic HIV infection was designed to
      evaluate whether sTNFR p55 and p75 at weeks 0 (pretreatment) and 24 and 48 are
      predictors of death < or = 3 years after the start of ZDV 1,000 mg alone or
      combined with low-dose interferon-alpha (ZDV 500 mg + IFN-alpha 3 MIU three times
      weekly). CD4+ T-cell numbers and serum neopterin were analyzed in a similar way.
      Forty previously untreated symptomatic HIV-infected persons with CD4+ T-cell
      numbers > or = 150 x 10(6)/L were included. At baseline, in the nonsurvivor
      group, mean age (42.1 vs. 34.4 years, p = 0.002) and neopterin (24.7 vs. 18.0
      nmol/L, p = 0.02) were higher, whereas mean CD4+ T-cell counts (202 vs. 295 x
      10(6)/L, p = 0.02) were lower than in the survivors. All analyses were adjusted
      for age. For the pretreatment marker values, a significant relative risk (RR) for
      death was noted only in the univariate analysis for sTNFR-p55 > 1.7 ng/ml [RR
      3.1; 95% confidence interval (CI) 1.1-8.8; p = 0.04]. During therapy, CD4+ counts
      < 200 x 10(6)/L at week 24 and 48 and neopterin > 20 nmol/ml at week 48 were
      independent predictors of survival in the uni- and multivariate analysis. Marker
      values relative to baseline were not predictive. sTNFR-p55 and p75 were of little
      use as surrogate markers for clinical efficacy during ZDV-containing drug
      regimens in symptomatic HIV-infected patients with CD4+ counts 150 x 10(6)/L.

PMID- 8757426
TI  - Menstrual function in human immunodeficiency virus-infected women without
      acquired immunodeficiency syndrome.
AB  - To assess whether HIV infection is associated with menstrual abnormalities in HIV
      infected women without AIDS, we evaluated 248 premenopausal HIV-infected women
      without AIDS and 82 HIV-negative women. Detailed medical, drug use, and menstrual
      histories (using menstrual calendars) were obtained. Complete physical and pelvic
      examinations and CD4 counts were performed. HIV-infected women were more likely
      to experience intervals > 6 weeks without menstrual bleeding [8 vs. 0%, odds
      ratio (OR) = 10.8, 95% confidence interval (CI) 1.8-1,000) and amenorrhea > 3
      months (5 vs. 0%, OR = 7.1, 95% CI 1.1-1,000) (after adjustment for drug use,
      age, and race). Premenstrual breast swelling (p = 0.01), tenderness (p = 0.01),
      and dysmenorrhea (p = 0.04) were less common in HIV-infected women. There were no
      differences in intermenstrual bleeding or irregular menstrual cycles. Among HIV
      infected women, only a past history of substance abuse was significantly
      associated with menstrual irregularities in a logistic regression model adjusting
      for age, current and past drug use, alcohol use, cigarette smoking, CD4 count,
      and category B conditions [1993 Centers for Disease Control (CDC) classification
      system]. The increase in amenorrhea (> 3 months) and in menstrual cycle intervals
      > 6 weeks and the lower rates of premenstrual breast symptoms in HIV-positive
      women suggest the possibility of disturbances in menstrual function that do not
      appear to be attributable to clinically apparent secondary complications of HIV.
      Changes in menstrual function were also significantly associated with a past
      history of, but not current, substance abuse, suggesting the possibility that
      socioeconomic factors rather than biologic effects of drugs may be responsible.

PMID- 8757427
TI  - Measuring HIV-1 incidence in northern Thailand: prospective cohort results and
      estimates based on early diagnostic tests.
AB  - Measuring the incidence of the human immunodeficiency virus (HIV) is of vital
      importance but can be difficult and costly. We compared HIV-1 incidence measured
      directly from prospective cohort studies with rates derived from a method using
      the prevalence of HIV-1 antibody-negative, p24-antigen-positive individuals. Male
      and female commercial sex workers (CSWs) were enrolled and followed in separate
      cohort studies in northern Thailand between 1989 and 1994, and HIV incidence was
      measured by prospective follow-up of individuals seronegative at baseline. In
      1991-1992 cross-sectional serosurveys were done among male and female CSWs in the
      same region; all HIV-1 antibody-negative subjects in these surveys were tested
      for p24 antigenemia. HIV incidence was estimated using the prevalence of p24
      antigen and a model based on the mean duration of p24 antigenemia before HIV
      antibody detection. The cohort studies showed high initial incidence rates
      23.8/100 person-years (PY) among female CSWs and 11.9/100 PY among male CSWs-but
      poor compliance with prospective follow-up. Subjects lost to follow-up appeared
      to be at greater risk of HIV seroconversion than those retained. The p24 antigen
      method estimate among female CSWs, 25.4%/year, was quite similar to the initial
      incidence rate found in the cohort. The estimate by the p24 antigen method was
      higher, 19.9%/year, among male CSWs than that measured prospectively. In
      populations with high rates of HIV transmission and in whom long-term follow-up
      is incomplete, estimates of incidence using p24 antigen prevalence among antibody
      negative subjects can give useful and economical estimates of HIV incidence and
      allow for estimates of whether the incidence rates are similar in subjects
      successfully followed and those lost to follow-up.

PMID- 8757429
TI  - Hospitalization of patients infected with active TB in New York State, 1987-1992:
      the effect of the HIV epidemic.
AB  - Hospital discharge records were used to study the relationship between human
      immunodeficiency virus (HIV) epidemic and hospitalized patients with tuberculosis
      in New York State from 1987 through 1992. The discharges of patients coinfected
      with HIV and tuberculosis increased by 270%, rising from 1,573 in 1987 to 5,825
      in 1992. This constitutes an increase from 19.8 to 49.1% of all discharges of
      patients with tuberculosis. Discharges of tuberculosis patients who were not
      infected with HIV decreased slightly during this time, going from 6,359 to 6,039.
      Postdischarge treatment plans, HIV prevention, HIV testing, and HIV educational
      programs for the tuberculosis population require special consideration, given the
      significant rise of HIV in the tuberculosis-infected population.

PMID- 8757428
TI  - Determinants of HIV infection among female commercial sex workers in northeastern
      Thailand: results from a longitudinal study.
AB  - Our objective was to estimate HIV seroconversion rates among commercial sex
      workers (CSWs) between 1990 and 1991 and to identify the behavioral, demographic,
      and reproductive determinants of these rates. This study has a prospective (n =
      240 with 15 cases) and a cross-sectional component (n = 271 with 34 cases). In
      November 1990, HIV-negative female CSWs from 24 brothels in Khon Kaen city were
      interviewed and were followed prospectively for up to 1 year. In March, June, and
      September 1991, additional HIV-negative CSWs were enrolled and prospectively
      followed. HIV seroconversion rates were calculated, and the Cox regression model
      was used to estimate the relative risks of HIV seroconversion from demographic,
      sexual practice, and reproductive factors, adjusted for the effects of the
      others, among 232 of the 240 without missing data. Seroprevalence rates were also
      calculated for the 271 participants enrolled between March and December 1991, and
      relative risks of HIV seroprevalence were calculated for demographic, sexual
      practice, and reproductive risk factors among 184 of the 271 without missing
      data. The average seroprevalence was 12.5% (95% confidence interval 9.6-15.4%).
      With 1,947 person-months of observation obtained from 240 participants who were
      uninfected at baseline and seen at least twice during the course of the study,
      the cumulative incidence of HIV seroconversion between November 1990 and December
      1991 was 9.4% (95% confidence interval 5.4-13.4%), and the average incidence rate
      of HIV seroconversion was 9.2 per 100 person-years (95% confidence interval 4.6
      13.9 per 100 person-years). In the multivariate analysis, later date of
      enrollment into the study, having < 3 months experience as a CSW, and use of
      injectable contraceptives were the only risk factors that remained significant,
      with relative risks of 2.1 (95% confidence interval 1.2-3.7) for enrollment 3
      months later, 3.8 (95% confidence interval 1.0-14.4) for < 3 months experience as
      a CSW versus > 3 months experience, and 3.9 (95% confidence interval 1.3-11.8)
      [corrected] for use of injectable contraceptives. In multivariate analysis of the
      cross-sectional data with 184 participants, of whom 21 were HIV seropositive,
      risk of HIV seropositivity increased significantly with current syphilis
      infection (odds ratio 5.8, 95% confidence interval 1.1-31.0). The results of this
      study will contribute to a better understanding of the risk factors of infection
      with HIV and thus allow for better targeting of group-specific interventions,
      particularly for CSWs and their clients. Further investigation of a possible
      association between injectable contraceptive use and HIV infection is needed.

PMID- 8757430
TI  - Weight loss associated with HIV seroconversion among injection-drug users.
AB  - To describe symptoms associated with human immunodeficiency virus (HIV)
      seroconversion, we studied a cohort of 366 injection-drug users (IDUs) with a
      study design that included recall every 3 months to collect symptom histories
      using a structured questionnaire. Eleven HIV seroconversions were observed in
      621.5 person years at risk (PYAR), equivalent to 1.8 seroconversions/100 PYAR.
      Cox regression analysis showed age < or = 35 years to be a significant risk
      factor for HIV seroconversion after controlling for gender, race, and the
      frequency of drug injection. An embedded case-control analysis then compared
      symptom histories of HIV seroconverters with those of age-(+/- 5 years) and visit
      number-matched controls who remained HIV seronegative for > or = 3 months longer
      than the HIV-seroconverters. Multivariate case-control analysis adjusted for
      injection frequency yielded significant associations of HIV seroconversion with
      histories of weight loss > or = 4.5 kg (seven of 11 cases; odds ratio [OR] =
      11.6, 95% confidence interval [CI] 3.1, 43.1) and oral ulcers (three of 11 cases;
      OR = 7.6, 95% CI = 1.2, 48.2) in the 3 months before the subjects' first HIV
      seropositive study visit. We conclude that histories of recent symptoms reported
      by HIV-seroconverting IDUs differ from those reported by non-HIV-seroconverting
      IDUs, and weight loss may be particularly common among IDUs experiencing primary
      HIV infection.

PMID- 8757431
TI  - Human T-cell lymphotropic virus type I infection in Barbados: results of a 20
      year follow-up study.
AB  - Forty-one human T-cell lymphotropic virus type I (HTLV-1)-seropositive
      individuals were identified among 1,012 subjects with stored serum samples from a
      health and seroepidemiological survey conducted in Barbados in 1972. These 41
      subjects plus 79 HTLV-1 seronegative household members were targeted in a follow
      up study 20 years later. Sixteen seropositive subjects and 22 seronegative
      subjects were interviewed, examined, and phlebotomized. There were no changes in
      HTLV-1 serostatus between the 1972 and follow-up serum samples. Three (19%) of
      the seropositive subjects had HTLV-1-associated disorders: two with dermatitis
      and one with "smoldering" adult T-cell leukemia. Neurologic and immunologic
      function was similar in HTLV-1-seropositive and HTLV-1-seronegative subjects.
      HTLV-1 antibodies persist over many years, and the risk for seroconversion of
      household contacts is low.

PMID- 8757432
TI  - Safety and feasibility of harvesting cells for adoptive immunotherapy from
      patients with asymptomatic HIV infection.

PMID- 8757433
TI  - HTLV-I/II survey on hemodialysis patients in Buenos Aires.

PMID- 8757434
TI  - Specificity of HTLV antibody enzyme immunoassay.

PMID- 8757435
TI  - Reactivity of Argentine serum samples against synthetic V3-based HIV-1 peptides.

PMID- 8757436
TI  - Viral/bacterial vaccination rates in HIV-infected patients.

PMID- 8757437
TI  - Presence of human T-cell lymphotropic virus types I and II infections in
      Honduras.

PMID- 8757438
TI  - Simple 1H NMR spectroscopic method for assay of salts of the contrast agent
      diatrizoate in commercial solutions.
AB  - A simple, accurate, and specific 1H NMR spectroscopic method was developed for
      the assay of diatrizoate meglumine or the combination diatrizoate meglumine and
      diatrizoate sodium in commercial solutions for injection. A mixture of injectable
      solution and sodium acetate, the internal standard, was diluted with D2O and the
      1H NMR spectrum of the solution was obtained. Two approaches were used to
      calculate the drug content, based on the integral values for the -N-CO-CH3
      protons of diatrizoic acid at 2.23 ppm, and -N-CH3 protons of meglumine at 2.73
      ppm, and the CH3-CO-protons of sodium acetate at 1.9 ppm. Recoveries (mean +/-
      standard deviation) of diatrizoic acid and meglumine from 10 synthetic mixtures
      of various amounts of these compounds with a fixed amount of internal standard
      were 100.3 +/- 0.55% and 100.1 +/- 0.98%, respectively. In addition to providing
      a direct means of simultaneously assaying diatrizoic acid and meglumine, the
      proposed NMR method can also be used to identify diatrizoate meglumine and each
      of its molecular components.

PMID- 8757439
TI  - Determination of lincomycin residue in salmon tissues by ion-pair reversed-phase
      liquid chromatography with electrochemical detection.
AB  - A method is described for detecting and quantitating lincomycin residue in salmon
      muscle and skin tissues by ion-pair reversed-phase liquid chromatography (LC)
      with electrochemical detection at +0.9 V. Lincomycin was extracted from tissues
      by homogenizing with 0.01 M KH2PO4 buffer (pH 4.5) and centrifuging the mixture.
      Water-soluble proteins were precipitated by adding sodium tungstate and sulfuric
      acid and removed by centrifugation. The buffer extract was then passed through a
      C18 solid-phase extraction cartridge. Lincomycin was eluted with 50% acetonitrile
      in water, and the eluate containing lincomycin was extracted with ethyl acetate.
      After the solvent had evaporated, the residue was redissolved in mobile phase and
      analyzed by LC. The method had a limit of detection of 7 ng/g lincomycin for
      salmon muscle and 12 ng/g for salmon skin. The limit of quantitation was 17 ng/g
      for salmon muscle and 24 ng/g for salmon skin. Average recoveries of lincomycin
      spiked at 50, 100, and 200 ng/g were > or = 85% for salmon muscle and > or = 80%
      for salmon skin.

PMID- 8757440
TI  - Determination of ceftiofur in bovine milk by liquid chromatography.
AB  - A liquid chromatographic procedure is described for determination of ceftiofur
      (CEF) residues in milk. Milk samples were diluted with ammonium acetate solution
      and extracted on a C18 solid-phase extraction (SPE) column. After the analyte was
      eluted from the SPE column with methanol, extract volumes were reduced under
      nitrogen, diluted to 2.0 mL with acetate buffer, and filtered. CEF was determined
      after separation of milk components by reverse-phase chromatography with UV
      detection at 293 nm. Recoveries of CEF from bovine milk fortified at 25, 50, and
      100 ppb were 86.1, 90.8, and 92.0%, respectively, with coefficients of variation
      (CVs) of 6.4, 7.3, and 3.9%, respectively. Values of CEF obtained from analysis
      of milk containing 2 levels of biologically incurred residues were 26.1 and 67.3
      ppb with CVs of 3.8 and 4.4%, respectively. The limits of detection and
      quantitation were estimated to be 4 and 7 ppb, respectively.

PMID- 8757441
TI  - Simultaneous determination of five fasciolicides in milk by liquid chromatography
      with electrochemical detection.
AB  - A sensitive and specific method is described for determination of 5 fasciolicides
      in milk. The drugs are used to control liver flukes in cattle. The milk sample
      was homogenized with acetone and acetonitrile, sonicated, and centrifuged. The
      supernatant was extracted with dichloromethane. The extract was evaporated to
      dryness, dissolved in 1% sodium hydrogen carbonate, and purified on a C18
      cartridge. The 5 drugs were separated from the matrix by reversed-phase liquid
      chromatography (LC) and determined by dual-electrode coulometric detection on a
      Kaseisorb LC ODS-300-5 column. The mobile phase was acetonitrile-0.05M potassium
      dihydrogen phosphate (55 + 45) at pH 3.0. The flow rate was 1 mL/min at 40
      degrees C. The applied potentials of detectors 1 and 2 were set at 0.20 and 0.55
      V, respectively. The average recovery of the drugs added to milk at 0.01 and 0.1
      micrograms/mL was 89.6%, and the coefficient of variation was 4.7%. The detection
      limits of the drugs in milk were 4-20 ng/mL. The method is used to monitor
      commercial milk samples and to determine the residual levels of these drugs in
      milk from cows treated with a fasciolicide.

PMID- 8757443
TI  - Evaluation of a rapid and automated enzyme-linked fluorescent immunoassay for
      detecting Escherichia coli serogroup O157 in cheese.
AB  - The Vitek Immunodiagnostic Assay System (VI-DAS) for Escherichia coli O157, a
      rapid and fully automated test, was evaluated for use in detecting the foodborne
      pathogen E. coli O157:H7 in soft, semisoft, and hard cheeses. Sixty-five cheese
      samples were artificially contaminated at low (2-4 colonyforming units [cfu]/25
      g) and high (7-10 cfu/25 g) levels with one of 2 strains of enterohemorrhagic E.
      coli O157:H7. Contamination at high levels was detected in all cheeses by VIDAS,
      whereas in 5 cheeses (7.7%) inoculated at low levels, contamination was not
      detected. In 15 additional cheeses inoculated with cold-stressed cells, both
      VIDAS and the Bacteriological Analytical Manual cultural assay detected all high
      and low levels of contamination. No false positives or interference from product
      background fluorescence was encountered in any of the cheeses tested by VIDAS.

PMID- 8757442
TI  - Usefulness of cellulase in recovery of Salmonella spp. from guar gum.
AB  - Most foods examined for Salmonella spp. by the procedure described in the U.S.
      Food and Drug Administration's Bacteriological Analytical Manual are preenriched
      at a 1:9 sample/broth ratio. However, 25 g guar gum (an emulsifying agent) is not
      wetted completely in 225 mL of preenrichment broth, and after a 24 h incubation
      at 35 degrees C, the product is transformed into a viscous, nonpipettable mass.
      The effects of 4 factors (inorganic salts, pH, temperature, and various enzymes)
      on the viscosity of the sample/preenrichment mixture during incubation were
      determined. Addition of various inorganic salts or adjustment of pH from 4.0 to
      9.0 had no significant effect on the viscosity of the incubated mixture. Elevated
      incubation temperatures of 42 degrees, 44 degrees, and 46 degrees C reduced
      viscosity but were well above the optimal growth temperature for Salmonella, 35
      degrees C. Addition of cellulose to lactose broth at a final concentration of
      0.01% reduced viscosity of the mixture, making it readily pipettable. At least
      one Salmonella cell was consistently recovered from 25 g samples of guar gum,
      which represents a most probable number value of 0.04 cell per g.

PMID- 8757444
TI  - Molecular detection of Clostridium botulinum type E neurotoxin gene in smoked
      fish by polymerase chain reaction and capillary electrophoresis.
AB  - The polymerase chain reaction (PCR), a rapid, sensitive technique for amplifying
      target DNA sequences of pathogenic microorganisms, was used to amplify
      Clostridium botulinum type E neurotoxin gene fragments in smoked fish. Other
      botulinal neurotoxin-producing strains, nontoxigenic strains, and food-related
      microorganisms did not yield nonspecific amplification products with this PCR
      assay. PCR products were analyzed by capillary electrophoresis (CE) using a low
      viscosity entangled polymer system. Resolution, sensitivity, and DNA sizing
      accuracy were improved, and analytical times were markedly shortened. The PCR/CE
      assay detected the C. botulinum type E neurotoxin gene in as few as 10 cells. The
      technique to other foods may also be a valuable tool for detecting foodborne
      pathogens.

PMID- 8757445
TI  - Use of urease-bromothymol blue-agar method for large-scale testing of urine on
      grain and seeds.
AB  - The current AOAC method (963.28) for large-scale (50 g) testing of urine on grain
      is based on the reaction of sodium in urine with magnesium uranyl acetate.
      Detection of sodium suggests that urine is present and that a test for urea is
      appropriate. Urea is detected with urease-bromothymol blue-paper and is confirmed
      through its reaction with xanthydrol to form dixanthylurea crystals, which are
      detected microscopically. The initial nonspecific test for sodium can be
      influenced by the presence of salt or other sodium compounds. Furthermore, the
      magnesium uranyl acetate spray used in Method 963.28 potentially exposes the
      analyst to the aerosol of a volatile, toxic uranium compound. Excess reagents and
      analyzed test portions must be disposed of as radioactive waste. In addition,
      Method 963.28 requires several steps to determine the presence of urea. The
      alternative AOAC method (972.41) tests for the presence of urea from urine on
      individual seeds. Urea is enzymatically decomposed to ammonia and carbon dioxide
      by urease. Liberated ammonia shifts the pH, changing the color of the indicator
      in the agar from yellow to blue. This study adapts Method 972.41 to larger test
      samples. Up to 25 g grains and seeds are sprayed with urease test agar instead of
      being individually immersed in the urease test agar. The modified method was used
      to analyze urea on seeds and grains of 24 plants from 4 families. The method has
      a limit of detection of one seed contaminated with 1 microgram urea.

PMID- 8757447
TI  - Determination and survey of deoxynivalenol in white flour, whole wheat flour, and
      bran.
AB  - A liquid chromatographic (LC) method for determining deoxynivalenol (DON) in
      white flour, whole wheat flour, and bran was developed. A 25 g test portion was
      extracted with acetonitrile-water (84 + 16), and the extract was filtered and
      applied to a column containing a combination of charcoal, Celite, and other
      adsorbents. The eluate was then chromatographed on a silica-based, reversed-phase
      LC column by using a gradient of water and methanol. DON was measured at 220 nm.
      Average recoveries of DON from white flour, whole wheat flour, and bran spiked at
      1 microgram/g were 88, 86, and 85%, respectively. The limit of determination of
      the method was < 0.5 micrograms/g. A total of 562 wheat-based products from the
      1993 crop year were collected by 21 U.S. Food and Drug Administration District
      Offices and analyzed by this method in Kansas City, Seattle, and New Orleans
      District Laboratories. The numbers of samples with DON contamination > or = 1
      microgram/g from 163 bran, 272 white flour, 90 whole wheat flour, and 37
      miscellaneous test samples were 20, 28, 14, and 2, respectively. About 52, 50,
      40, and 27% of the same test samples were contaminated with DON at levels > 0.01
      micrograms/g.

PMID- 8757446
TI  - Mycotoxins transmitted into beer from contaminated grains during brewing.
AB  - Studies with aflatoxin B1, ochratoxin A, zearalenone, deoxynivalenol, and
      fumonisins B1 and B2 added at various stages of the brewing process show that
      these mycotoxins (or metabolites) may be transmitted from contaminated grains
      into beer. Citrinin does not survive the mashing step. Mycotoxins in beer could
      originate from the malted grain or from adjuncts. Although high incidences and
      concentrations of aflatoxins and zearalenone have been found in local beers
      brewed in Africa, aflatoxins have not been detected in European beers.
      Zearalenone and alpha- or beta-zearalenol (the metabolite likely to occur) have
      not been found in Canadian and European beers, except for one sample analyzed by
      thin-layer chromatography only. Ochratoxin A rarely has been detected at > 1
      ng/mL in beer; liquid chromatographic methods with a 0.05-0.1 ng/mL detection
      limit, however, have shown moderately high incidences of trace levels.
      Deoxynivalenol, which survives the brewing process, has been found with high
      incidence in Canadian and European beers, with concentration of > 200 ng/mL
      reported in several German beers. Fumonisins B1 and B2 occur to a limited extent
      in beer.

PMID- 8757448
TI  - Supercritical fluid extraction of volatile N-nitrosamines in fried bacon and its
      drippings: method comparison.
AB  - N-Nitrosopyrrolidine (NPYR) and N-nitrosodimethylamine (NDMA), known animal
      carcinogens, are consistently formed in bacon during frying. As a result,
      commercial bacon has been subject to regulatory monitoring and compliance for the
      past 20 years to ensure that N-nitrosamines do not exceed the 10 ppb volatile
      level. Currently, time-consuming distillation-solvent extraction and solid-phase
      extraction (SPE) methods are used for this purpose. With an emphasis on reducing
      solvent use, we investigated supercritical fluid extraction (SFE) using
      supercritical carbon dioxide (SC-CO2) for isolation of volatile nitrosamines
      common to fried bacon. Eighteen fried bacon samples were analyzed for NPYR and
      NDMA by SFE, SPE, mineral oil distillation (MOD), and low-temperature vacuum
      distillation (LTVD) methods, using the same gas chromatographic-chemiluminescence
      detection (thermal energy analyzer) conditions. The range of values for SFE was
      0.7 to 20.2 ppb for NPYR and none detected (ND) to 2.4 ppb for NDMA. Analysis of
      variance of the NPYR data showed a significant difference (p < 0.05) between SFE
      and SPE results and significant differences between these and those obtained by
      MOD and LTVD. Overall, SFE was superior to the other methods with the highest
      recoveries, best repeatability, rapidity of analysis, and solvent-sparing
      characteristics. Similar results were obtained for SFE after comparison with
      distillation and SPE methods for determining the same nitrosamines in fried bacon
      drippings.

PMID- 8757449
TI  - Liquid chromatographic determination of tocopherols and tocotrienols in
      margarine, infant foods, and vegetables.
AB  - A liquid chromatographic (LC) method was developed for determination of
      tocopherols and tocotrienols in foods. Tocopherols and tocotrienols were released
      after saponification of test portions for 40 min at 80 degrees C, followed by
      extraction with hexane-ethyl acetate. After evaporation of the organic solvents,
      the extract was injected in the LC system. Separation of individual tocopherols
      and tocotrienols was satisfactory. Some interferences were encountered from
      tocomoneols, tocodienols, 2-tert-butyl-4-hydroxyanisole (BHA), 2,6-di-tert-butyl
      4-methylphenol, (BHT), and plastochromanol-8. The response of the LC system was
      linear over a range of 0-10 micrograms/mL for tocopherols and tocotrienols. The
      detection limit for these compounds was 0.1 micrograms/mL. Repeatabilty relative
      standard deviation values for tocopherols and tocotrienols in margarine, infant
      formula, and broccoli (concentration range, 0.11-22 mg/100 g) varied from 1.3 to
      6.4%. Recoveries ranged from 91 to 105%.

PMID- 8757450
TI  - Comparison of Babcock and ether extraction methods for determination of fat
      content of cream: collaborative study.
AB  - A modified Mojonnier ether extraction method for determination of the fat content
      of cream was developed based on the method for milk (AOAC Official Method
      989.05). The cream Babcock method (AOAC Official Method 920.111B-C) was modified
      to harmonize with the milk Babcock method (AOAC Official Method 989.04) and to
      clarify procedural details. Using the AOAC collaborative study format, 10
      laboratories tested 9 pairs of blind duplicate heat-treated cream samples with a
      fat range of 30-45% using both methods. The statistical performance (invalid and
      outlier data removed) was as follows: mean % fat = 37.932, Sr = 0.125, SR =
      0.151, RSDr = 0.330, RSDR = 0.398, r = 0.354, and R = 0.427 for the ether
      extraction method. For the Babcock method, mean % fat = 38.209, Sr = 0.209, SR =
      0.272, RSDr = 0.548, RSDR = 0.712, r = 0.592, and R = 0.769. Average test results
      for fat from the Babcock method were 0.277% (absolute fat) greater than for the
      Mojonnier ether extraction method. The difference between methods, as a
      percentage of the average fat content of the samples, was 0.73%. This agrees with
      differences observed between the 2 methods for milk when 10 to 17 laboratories
      tested 7 milk samples in blind duplicate at bimonthly intervals over a 4-year
      period (average difference 0.029% fat, 0.78% as a percentage of average fat
      content). The Mojonnier ether extraction and Babcock methods for fat in cream
      have been adopted by AOAC INTERNATIONAL. The new Babcock method replaced the AOAC
      Official Method 920.111B-C.

PMID- 8757451
TI  - Detection of added beet sugar in concentrated and single strength fruit juices by
      deuterium nuclear magnetic resonance (SNIF-NMR method): collaborative study.
AB  - A collaborative study of the site-specific natural isotope fractionation-nuclear
      magnetic resonance (SNIF-NMR) method for detecting added beet sugar in fruit
      juices is reported. This method is complementary to the stable carbon isotope
      ratio analysis (SCIRA) (AOAC Official Methods 981.09 and 982.21), which can
      detect sugars derived from plants exhibiting C4 metabolism (corn and sugarcane).
      It is based on the fact that the deuterium content at specific positions of the
      sugar molecules is higher in fruit sugars than in beet sugar. The fruit juices
      are fermented, and the alcohol is distilled with a quantitative yield and
      analyzed with a high-yield NMR spectrometer fitted with a deuterium probe and
      fluorine lock. The proportion of ethanol molecules monodeuterated on the methyl
      site is recorded. This parameter (D/H)I is lowered when beet sugar is added to a
      fruit juice or concentrate. The precision of that method for measuring (D/H)I was
      observed to be similar to that of other isotope ratio methods: Sr values ranged
      from 0.19 to 0.25 ppm and SR values varied between 0.21 and 0.37 ppm. An
      excellent correlation was observed between the percentage of added beet sugar and
      the (D/H)I isotope ratio measured in this collaborative study. Consequently, all
      samples in which beet sugar was added were found to have a (D/H)I isotope ratio
      significantly below the normal value for authentic juice or concentrate of that
      fruit. The SNIF-NMR method for detection of added beet sugar in fruit juices has
      been adopted by AOAC INTERNATIONAL.

PMID- 8757452
TI  - Use of solid-phase extraction disks for analysis of moderately polar and nonpolar
      pesticides in high-moisture foods.
AB  - This study investigated the use of solid-phase extraction (SPE) disks in analysis
      of high-moisture (< 2% fat) foods for organophosphorus and organochlorinated
      pesticides with low (< 25 mg/mL) water solubilities. Five representative foods
      were each spiked with one of 18 pesticides at 2 levels. Gas chromatography with
      flame photometric and electrolytic conductivity detection was used to quantitate
      organophosphates and organochlorinated pesticides, respectively. Essentially
      complete recoveries (> or = 80%) suggest that use of SPE disks can complement
      traditional liquid-liquid extraction procedures.

PMID- 8757453
TI  - Organochlorine and organophosphorus pesticide residues in food from Egyptian
      local markets.
AB  - A market basket survey was conducted to monitor organochlorine and
      organophosphorus pesticide residues in potatoes, citrus fruits, and fish
      collected from local Egyptian markets. Maximum Residue Limits (MRLs) of the Codex
      Committee on Pesticide Residues for gamma-hexachlorocyclohexane (HCH) in potatoes
      were exceeded in 8 samples and for DDT in 2 samples. The aging of HCH and DDT
      indicated a recent use of both pesticides during the potato storage period
      between cultivation seasons. However, such use is illegal because HCH mixture
      isomers (gammaxane) and DDT have been officially prohibited from agricultural use
      in Egypt since 1980. The highest residue levels of fenitrothion (3.8 ppm) in
      potatoes may be due to its repeated use before and after harvest. No
      organochlorine pesticide residues were found in citrus fruits. None of the
      detected organophosphorus pesticides exceeded their MRLs. HCH and DDT residue
      limits were exceeded in 5 and 7 fish samples, respectively, collected from 12
      markets throughout the country. The heptachlor MRL was violated in only one fish
      sample (3.9 ppm).

PMID- 8757454
TI  - Modular methodology for determination of polychlorinated biphenyls in soil as
      Aroclors and individual congeners.
AB  - A comprehensive screening and confirmatory method was developed for monitoring
      polychlorinated biphenyls (PCBs), both as Aroclors and as individual congeners.
      This approach incorporates extraction, extract cleanup, and analysis modules
      designed to match cost, time, and data quality requirements. Soxhlet, sonication,
      supercritical fluid, and accelerated solvent extractions were evaluated. Carbon
      chromatographic cleanup procedures were used for separation of congeners on the
      basis of ortho substitutions, which permitted calculation of toxicity
      equivalents. Individual congener determinations, congener total histograms, and
      peak comparison techniques for Aroclor identification were elaborated by using
      high and low resolution mass spectrometric data. A screening procedure based on
      immunoassay using the Ohmicron PCB RaPID Assay kit gave results comparable to
      those obtained by gas chromatography with electron capture detection in the range
      0.40-230 ppm, when the appropriate Aroclor calibrator was used.

PMID- 8757455
TI  - Determination of total free and glucose-conjugated 3-phenoxybenzyl alcohol
      residues in foods by gas chromatography with electron capture detection.
AB  - A method was developed to determine the combined amounts of residual, free 3
      phenoxybenzyl alcohol (permethrin alcohol) and its acetone-extractable glucosides
      in representative fruits and vegetables after application of pyrethyroid
      insecticides such as permethrin or cypermethrin. 3-Phenoxybenzyl glucoside was
      synthesized and used to spike food samples. Conditions were developed for
      extraction, enzymatic hydrolysis, derivatization with heptafluorobutyric
      anhydride, and cleanup prior to detection and quantitation by gas chromatography
      with electron capture detection. Limits of detection in various foods were < or =
      0.01 ppm. In addition, 2 sets of field trial samples that were sprayed with
      permethrin and collected at intervals were also analyzed. In general, the amounts
      of total permethrin alcohol in foods were small.

PMID- 8757456
TI  - Levels of Cd, Hg, As, Cu, Mn, and Zn in Japanese restaurant and box lunches.
AB  - Intakes of selected elements from restaurant and box lunches in Shiga Prefecture
      (Japan) were investigated in 1993 and 1994, respectively. Average intakes of
      these elements from restaurant and box lunches were, respectively, 14 and 12
      micrograms for Cd, 4.6 and 4.5 micrograms for Hg, 85 and 91 micrograms for As,
      461 and 561 micrograms for Cu, 1268 and 1235 micrograms for Mn, and 3612 and 2688
      micrograms of Zn. There were no great differences between the intakes from the
      restaurant lunches in 1993 and the box lunches in 1994. The proportion of
      elements from the lunches constituted 25-38% of the daily intake for Cd, As, Mn,
      and Zn and 51-65% of the daily intake for Hg.

PMID- 8757457
TI  - Homogeneity of fruits and vegetables comminuted in a vertical cutter mixer.
AB  - The homogeneity of comminuted composites of 20 lb samples of apples, cabbage, and
      green beans containing field-incurred residues of p, p'-methoxychlor was studied
      to determine whether a 5 min comminution in a 40 qt vertical cutter mixer
      produces a homogeneous composite and whether the size of test portions used
      accurately represents the composite. Duplicate test portions of 100, 50, 25, 10,
      5, and 2 g taken from each of 6 separate sections of the mixer were analyzed by
      standard pesticide residue methodology for p, p'-methoxychlor. Results of this
      study confirmed that comminution of fresh produce in a 40 qt vertical cutter
      mixer, according to instructions described in the U.S. Food and Drug
      Administration's Pesticide Analytical Manual, Volume I, Section 203B, produces a
      homogeneous composite. No significant differences were found in the data for the
      3 crops taken from the 6 sections of the mixer. Test portion weights of 100, 50,
      and 25 g produced equivalent results for all 3 crops. Statistically significant
      differences were observed for cabbage at 2, 5, and 10 g and for green beans at 2
      g.

PMID- 8757458
TI  - Improvement of calibration curve for determining peroxide values of food lipids
      by the modified ferrous oxidation-xylenol orange method.
AB  - The linearity range of the standard Fe(+3) calibration curve for measuring lipid
      hydroperoxides in food samples by the modified ferrous oxidation-xylenol orange
      (mFOX) method was extended from 5-20 micrograms to 2-40 micrograms by
      establishing the best concentration of xylenol orange in the same assay system.
      Butter, fish oil, and some vegetable oils were analyzed by the International
      Dairy Federation method and the improved mFOX method, and results were compared.

PMID- 8757459
TI  - Effect of USP apparatus 1 and 2 at different rotational speeds on dissolution of
      niacin formulations.
AB  - Forty-four niacin formulations were examined by the United States Pharmacopeia
      dissolution test, consisting of 0.1N HCl with apparatus 1 and 2. Each formulation
      was tested with apparatus 1 (basket) at 100 rpm and apparatus 2 (paddle) at 50
      and 100 rpm. Dissolution results varied widely among manufacturers.

PMID- 8757460
TI  - Alternative site testing.

PMID- 8757461
TI  - Central nervous system Mycobacterium avium complex infection.

PMID- 8757462
TI  - Designing critical limit systems for knowledge optimization.

PMID- 8757463
TI  - Do discrepancies exist in serum osmolal gaps and calculated serum alcohol
      concentrations? The significance to the clinician and clinical pathologist.

PMID- 8757464
TI  - Laboratory precision performance: state of the art versus operating
      specifications that assure the analytical quality required by clinical laboratory
      improvement amendments proficiency testing.
AB  - OBJECTIVE: To estimate the percent of laboratories with precision performance
      sufficient to satisfy the operating specifications and guarantee the quality
      required by the proficiency testing criteria defined by the Clinical Laboratory
      Improvement Amendments of 1988 (CLIA). DESIGN: Cumulative distributions that
      describe state-of-the-art laboratory imprecision were obtained for 1500
      laboratories participating in the 1990 College of American Pathologists Quality
      Assurance Service. Allowable imprecision was estimated from the x-intercepts of
      charts of operating specifications prepared for commonly used single and
      multirule quality control procedures having two to four control measurements per
      run. MAIN OUTCOME MEASURE: The derived values for allowable imprecision were
      imposed on the cumulative distributions to obtain graphical estimates of the
      percent of laboratories satisfying the operating specifications. RESULTS: Up to
      28% of laboratories achieve the imprecision allowable for albumin, up to 64% for
      total bilirubin, 52% for calcium, 35% for chloride, 48% for cholesterol, 28% for
      cortisol, 84% for creatinine, 9% for digoxin, 61% for glucose, 64% for high
      density lipoprotein cholesterol, 88% for hemoglobin, 95% for potassium, 66% for
      total protein, 18% for sodium, 29% for thyroxine, 87% for triglycerides, 35% for
      urea nitrogen, and 81% for uric acid. CONCLUSION: Improvements in precision are
      still needed for many laboratory tests to assure the analytical quality required
      by the CLIA proficiency testing total error criteria.

PMID- 8757465
TI  - Laboratory computer availability: a College of American Pathologists Q-probes
      study of computer downtime in 422 institutions.
AB  - OBJECTIVE: To determine the frequency, duration, and impact of computer downtime
      on laboratory operations. METHODS: Four hundred twenty-two laboratories monitored
      the frequency of computer system downtime and other computer malfunctions over a
      period of 30 days. Participants classified each instance of unavailability
      according to its cause, duration, and consequences. In all, data from 11 967
      instances were submitted for analysis. RESULTS: During the 30-day study period,
      the participating institutions experienced a median of eight episodes in which
      all or a primary computer function was unavailable. The cumulative median
      duration of downtime during these 30 days was 14.3 hours. The most unfortunate
      10% of participants reported having 44 or more episodes in which all or a primary
      computer function was lost during the 30 days, for a cumulative duration of 77.7
      or more hours of system unavailability. Computer installations that served two or
      more full-service laboratories were significantly more likely to experience
      unscheduled loss of all or a primary computer function than were sites that
      served only one laboratory, and unscheduled events were more likely to be of
      longer duration. Participants reported that 1.3% of downtime events required the
      use of staff overtime to perform required work. Overtime was more likely with
      longer-than-average periods of downtime and losses that had not been scheduled.
      Of all the downtime instances, 0.2% led to the release of inaccurate results, and
      0.1% led to an adverse clinical outcome. These events were associated with
      software failure, unscheduled downtime, a site's overall frequency of downtime,
      particular software vendors, and not having installed a software patch in the
      previous 1000 days. CONCLUSIONS: The frequency of laboratory computer downtime
      varies widely among institutions and is occasionally associated with adverse
      clinical outcomes or additional staff expense.

PMID- 8757466
TI  - Evaluation of a laboratory critical limit (alert value) policy for hypercalcemia.
AB  - OBJECTIVE: To evaluate a laboratory critical limit policy for hypercalcemia
      requiring the laboratory to notify the physician for any serum calcium level
      higher than 2.99 mmol/L (12.0 mg/dL). DESIGN: The protocol was assessed using the
      following criteria: recognition, treatment (fluids or drugs) or no treatment of
      hypercalcemia, and the effect of adopting lower (2.64 mmol/L) or higher (3.22
      mmol/L) calcium critical limits. RESULTS: Patients were divided into four groups:
      group 1, 2.64 to 2.74 mmol/L (n = 131); group 2, 2.77 to 2.87 mmol/L (n = 33);
      group 3, 2.89 to 2.99 mmol/L (n = 16); and group 4, higher than 2.99 mmol/L (n =
      11). Hypercalcemia was recognized in 48%, 55%, 56%, and 100%; treated with fluids
      in 0%, 0%, 6%, and 9%; treated with drugs in 0%, 0%, 0%, and 73%; and not treated
      in 100%, 100%, 94%, and 18% of patients in groups 1 through 4, respectively.
      Lower calcium critical limits of 2.64, 2.77, and 2.89 mmol/L would lead to an
      increase of 1371%, 442%, and 142% in telephone calls. A higher calcium critical
      limit of 3.22 mmol/L would have resulted in not notifying the physician of six
      patients (60%) who were treated for hypercalcemia. CONCLUSIONS: The present
      hypercalcemia policy is effective because patients with calcium levels below 2.99
      mmol/L (< 1%) are rarely treated for hypercalcemia and because lowering the
      calcium critical limit alert value would not increase physician awareness of
      hypercalcemic patients. It would, however, result in a significant increase in
      telephone calls. A higher calcium critical limit (3.22 mmol/L) would potentially
      result in missing a significant number of hypercalcemic patients in need of
      therapy.

PMID- 8757467
TI  - Discrepancies in osmolal gaps and calculated alcohol concentrations.
AB  - OBJECTIVES: To estimate unexplained osmolal gaps (UEOG) during ethanol ingestions
      after accounting for measured ethanol concentrations and to explore the causes of
      observed discrepancies. DESIGN AND SPECIMENS: A random convenience sample of
      serum specimens with a request to perform osmometry for the detection of alcohols
      was studied. MAIN OUTCOME MEASURES: Serum concentrations of sodium, glucose, urea
      nitrogen, ethanol, osmolality, and ethanol were measured by two analytic methods
      to determine calculated osmolalities and osmolal gaps using two commonly used
      formulas. RESULTS: In 79 serum specimens submitted for osmometry, mean ethanol
      concentrations were 199 +/- 154 (SD) mg/dL; 15 specimens had no detectable
      ethanol. After regression of the calculated ethanol concentrations and the
      measured ethanol concentrations, the Dorwart and Chalmers formula showed a large
      constant bias of 45.217 +/- 6.414 (SE) mOsm/kg in predicting measured ethanol
      concentrations. The Smithline and Gardner formula was similarly as precise (r =
      .9786), but had a much smaller bias of -3.929 +/- 6.623 (SE) mOsm/kg. Actual mean
      differences between measured and calculated osmolalities (including ethanol
      osmols) gave an estimate of UEOG seen during ethanol ingestions. Using the less
      biased formula, the mean UEOG was 1.4 +/- 8.5 mOsm/kg, giving a 95% upper limit
      of the reference range of 18 mOsm/kg in this population with ethanol ingestions.
      Three significant outliers were identified and their UEOG could be explained by
      the presence of mannitol, isopropanol, or possibly a change in the assumed value
      for fractional water, normally a constant in these formulas for calculated
      osmolality. Other specific causes of osmolal gap and UEOG are discussed.
      CONCLUSION: The potential range of osmolal gaps seen during ethanol ingestions
      after accounting for ethanol is demonstrated to be greater than in previous
      studies, which have included a lower proportion of ethanol-intoxicated subjects
      in their study sample.

PMID- 8757468
TI  - Pneumatic transport exacerbates interference of room air contamination in blood
      gas samples.
AB  - OBJECTIVE: To characterize and control the potential interference to P(O2)
      determinations when blood contaminated with air is sent via a pneumatic tube
      system (PTS). DESIGN: Both tonometered blood at P(O2)s of 65, 75, 142, and 339 mm
      Hg and arterial blood gas samples from patients with baseline P(O2)s from 70 to
      400 mm Hg were analyzed for P(O2) to determine possible effects of air
      contamination from PTS transport. SETTING: A large teaching hospital in which a
      variety of personnel routinely send samples to the laboratory by PTS transport.
      PATIENTS: Twenty patients under anesthesia for elective surgery and 21 patients
      in an intensive care unit who had a wide range of P(O2)s. Several additional
      patients with a preexisting lung pathology likely to cause hypoxemia were
      selected to provide samples with low P(O2)s. MAIN OUTCOME MEASURES: Measurement
      of bias in P(O2) between samples sent via PTS and samples walked to the
      laboratory. RESULTS: Interference from air contamination was worse after PTS
      transport compared with manual transport of the specimen. Over a wide range, the
      P(O2) in specimens after PTS transport tended toward 160 mm Hg. Samples from
      hypoxemic patients were prone to errors in P(O2) that could have resulted in
      clinical misinterpretation; 5 of 10 samples with a baseline P(O2) less than 85 mm
      Hg had increases of 10 mm Hg or more when contaminated with air. Cooling samples
      with high P(O2)s minimized changes to P(O2), probably by increasing the
      solubility of oxygen. Mechanical buffering by various liners used in the carriers
      did little to alleviate the interference. Decreasing the speed of pneumatic
      transport by 50% lessened the effect on P(O2). CONCLUSION: Interference can be
      minimized by carefully purging samples of all air bubbles using the following
      protocol: invert syringe to check for air bubbles, then retap and reexpel bubbles
      if necessary. Personnel that collect and send blood gas samples via PTS should be
      educated about the problem of interference. Modifications both to pneumatic
      sample transport systems and to blood gas syringes should be investigated to
      minimize the effect.

PMID- 8757469
TI  - Serum bilirubin pigments covalently linked to albumin.
AB  - The serum levels of biliprotein (i.e., the bilirubin fraction covalently linked
      to albumin) were measured in patients with hepatobiliary disease by two
      analytical procedures: reverse-phase anion-exchange chromatography (Bond-Elut)
      and anion-exchange chromatography. Bond-Elut extracts contained tetrapyrroles,
      allowing the analysis of biliprotein, bilirubin, and bilirubin conjugates,
      whereas the anion-exchange method converted tetrapyrroles to azodipyrroles
      (protein-free), which were adsorbed on the resin, with the exception of
      azopyrrole of biliprotein (covalently linked to albumin), which passed through
      the resin and could be analyzed. In contrast, other cationic polymer columns did
      not completely bind the alkaline diazo derivatives of unconjugated bilirubin,
      conjugated bilirubin, or the azopyrrole of biliprotein not bound to albumin.
      Therefore, a comparison was made of these two methods using the original anion
      exchange resin. Both procedures gave similar values for serum levels of
      biliprotein in patients with high levels of total bilirubin.

PMID- 8757470
TI  - An immunohistochemical study of the simultaneous expression of bcl-2 and p53
      oncoproteins in epithelial tumors of the colon and rectum.
AB  - OBJECTIVE: Bcl-2 and p53 genes may participate in a common pathway for regulation
      of apoptosis. The aims of this study were (1) to study the immunohistochemical
      expression of the bcl-2 oncoprotein in colorectal tumors, (2) to correlate it
      with that of p53 protein overexpression, and (3) to compare it with
      histopathologic prognostic factors, such as TNM classification and grade. DESIGN:
      Prospective study of expression of bcl-2 and p53 oncogenes in colorectal tumors.
      We examined 6 colorectal hyperplastic polyps, 33 adenomas, and 61 carcinomas.
      SETTING: Regional academic medical center. METHODS: An immunohistochemical study
      with bcl-2 and p53 antibodies was performed on frozen sections of colorectal
      tumors. The levels of bcl-2 and p53 expression were evaluated using a
      semiquantitative grading system. Two-color immunohistochemistry was performed to
      examine the intracellular colocalization of bcl-2 and p53 in all tumors with a
      strong positivity for both antigens. RESULTS: Bcl-2 was expressed in 28 (85%) of
      the 33 adenomas, whereas p53 was expressed in only one adenoma, which had areas
      of in situ carcinoma. Bcl-2 and p53 were each expressed in 43 (70.4%) of the 61
      carcinomas. Thirty-one (50%) of the colorectal carcinomas coexpressed the two
      oncoproteins. There was no correlation between the number of cells expressing bcl
      2 and the number expressing p53 in a given carcinoma. No correlation was observed
      between the expression of bcl-2 or p53 and the established prognostic factor.
      CONCLUSION: Abnormal bcl-2 oncoprotein expression appears earlier than p53
      accumulation in colorectal carcinogenesis. This study suggests that there is more
      than one sequence and mechanism of bcl-2 and p53 gene deregulation in colorectal
      carcinomas.

PMID- 8757472
TI  - Familial peeling skin syndrome with eosinophilia: clinical, histologic, and
      ultrastructural study of three cases.
AB  - OBJECTIVE: The clinicopathologic features of a rare familial form of congenital
      blister are analyzed to assess what factors could lead to the cutaneous split.
      METHODS: Three consanguinous newborn babies had a congenital ichthyosis with
      eosinophilia and elevated total immunoglobulin E. The type and level of the split
      were studied on skin biopsies performed on the first day of life. RESULTS: The
      level of the split was located within the corneocytes. Isolated eosinophilic
      granules were found at this site. Desmosomes and the dermoepidermal junction were
      intact. Blisters and eosinophilia resolved in 3 weeks, and there was no
      recurrence during 4 and 6 years of follow-up in two of the patients. CONCLUSION:
      Peeling skin syndrome is a rare blistering disorder of the newborn that should be
      recognized because it has a good prognosis. Eosinophils may play an important
      role in the cutaneous split of this congenital ichthyosis.

PMID- 8757471
TI  - The reactions of euthyroid and hyperthyroid glands to radioactive iodine.
AB  - BACKGROUND: Researchers generally assume that the thyroid gland reacts more or
      less comparably to external irradiation and radioactive iodine. DESIGN: The
      thyroid glands from 20 euthyroid patients and 20 hyperthyroid patients, all of
      which had been treated with radioactive iodine, were studied. RESULTS: The two
      groups manifested different reactions. Almost all the euthyroid glands displayed
      a fibrotic atrophic pattern, whereas the glands from the Graves' disease patients
      showed more adenomatous and Hashimoto lesions than atrophy. CONCLUSION:
      Differences in the reactivity of normal and hyperplastic follicles may cause
      different reactions to treatment with radioactive iodine.

PMID- 8757473
TI  - Heterotopic bone formation in the gastrointestinal tract.
AB  - Heterotopic bone is found rarely in the gastrointestinal tract. Here we report
      four cases, one of which occurred in Barrett's esophagus in an area of metaplasia
      of specialized cell type without evidence of neoplasia. In the remaining cases,
      bone was associated with mucin-producing tumors of the appendix, transverse
      colon, and rectum. The clinical and pathologic findings are discussed in detail.
      Heterotopic bone formation in the digestive tract usually occurs in the
      colorectum in association with benign or malignant epithelial tumors, and most
      often with those that produce abundant mucin. The pathogenesis of the osseous
      metaplasia in the gastrointestinal tract is not understood, although mucin
      extravasation is an almost constant feature. Fragments of metaplastic bone in a
      biopsy of a mucinous neoplasm of the digestive tract should not be misinterpreted
      as osseous invasion.

PMID- 8757474
TI  - Primary leiomyosarcoma of bone: report of seven cases and review of the
      literature.
AB  - OBJECTIVE: To report seven cases of intraosseous leiomyosarcoma and compare them
      with the cases in the literature. DESIGN: Retrospective review of histologic,
      immunohistochemical, and ultrastructural features. Tumors were examined
      immunohistochemically for proliferative activity and p53 protein accumulation.
      SETTING: Mount Sinai Hospital, University of Toronto, Ontario, Canada. RESULTS:
      The histologic grade of the tumors ranged from I to III. All tumors showed
      vimentin and muscle-specific actin immunoreactivity and smooth muscle
      differentiation ultrastructurally. Proliferative activity was demonstrated
      immunohistochemically in five of the seven cases. Only one tumor showed p53
      protein accumulation. CONCLUSION: Primary leiomyosarcoma of bone is an aggressive
      tumor with light microscopic, ultrastructural, and immunohistochemical features
      similar to leiomyosarcoma of soft tissue. The proliferative activity of these
      tumors does not appear to correlate with the histologic grade. p53 protein
      accumulation as detected by immunostaining is not common in these tumors.

PMID- 8757475
TI  - Epithelioid cells in myoid hamartoma of the breast: a potential diagnostic
      pitfall for core biopsies.
AB  - OBJECTIVE: We report six cases of myoid hamartoma of the breast, a rare benign
      lesion in which the characteristic smooth muscle cells may have epithelioid
      histology. We emphasize the importance of radiographic correlation and
      immunohistochemical studies to diagnosis, particularly on stereotactic core
      biopsies, to avoid potential confusion with infiltrating lobular carcinoma.
      DESIGN: Case studies. Prospective and retrospective analysis of six cases,
      including stereotactic biopsy of two. SETTING: Academic medical center-based
      pathology practice. PATIENTS: Six postmenopausal women, aged 50 to 59 years, with
      palpable or nonpalpable mammographically evident breast masses. RESULTS: All the
      lesions were radiographically well circumscribed, most showing heterogeneous
      radiodensity. Histologically variable amounts of glandular, fibrous, and adipose
      tissue were admixed with smooth muscle cells, which occasionally had prominent
      epithelioid features. All the lesions' myoid cells stained for smooth muscle
      markers as well as steroid receptor proteins. Stereotactic core biopsy was
      diagnostic in one case, making excision unnecessary. CONCLUSIONS: With proper
      radiographic correlation and immunohistochemical confirmation, myoid hamartoma
      can be confidently diagnosed even on the limited tissue samples yielded by
      stereotactic core biopsy.

PMID- 8757476
TI  - Lipomas of the internal auditory canal.
AB  - Lipoma of the internal auditory canal is a rare tumor that may be confused
      clinically with the much more common vestibular schwannoma. We present two cases
      of lipoma of the internal auditory canal. The clinical presentation is
      indistinguishable from that of vestibular schwannomas. The high signal intensity
      on T1-weighted magnetic resonance imaging, both with and without contrast, is
      consistent with other reports of lipoma. Review of the literature shows that
      lipomas of the internal auditory canal are histopathologically similar to lipomas
      of the cerebellopontine angle. The symptoms, erosive effect on the auditory
      canal, and gross appearance of this uncommon tumor are sometimes difficult to
      differentiate from those of a vestibular schwannoma. The diagnosis can be
      established by intraoperative examination of frozen sections.

PMID- 8757477
TI  - Hemolysis due to the simultaneous occurrence of passenger lymphocyte syndrome and
      a delayed hemolytic transfusion reaction in a liver transplant patient.
AB  - Hemolysis due to donor-derived antibodies produced by "passenger" B lymphocytes,
      called passenger lymphocyte syndrome, has been described in ABO-unmatched solid
      organ and bone marrow transplant recipients. Delayed hemolytic transfusion
      reactions occur within a similar time frame and have similar clinical and
      serologic findings. To our knowledge, we report the first case of hemolysis due
      to the simultaneous occurrence of passenger lymphocyte syndrome (donor-derived
      anti-A) and a delayed hemolytic transfusion reaction (recipient-produced anti-E)
      in a liver transplant patient.

PMID- 8757479
TI  - Recurrent intermetatarsal neuroma. A follow-up study.
AB  - Sixteen patients were evaluated following excision of recurrent intermetatarsal
      neuroma. Each underwent removal of a segment of nerve through an incision on the
      plantar aspect. The nerve stump was buried in the flexor digitorum brevis muscle.
      At the time of follow-up examinations, six patients were asymptomatic, seven
      experienced mild pain after extended activity, one suffered mild consistent pain
      with activity, and two suffered pain that limited activities.

PMID- 8757478
TI  - Yolk sac tumor of the liver combined with hepatocellular carcinoma.
AB  - Hepatic yolk sac tumor is extremely rare, and only nine cases have been reported
      previously to our knowledge. We report the occurrence of a tumor combining
      hepatocellular carcinoma and yolk sac tumor. The clinical, pathologic, and
      immunohistochemical findings are presented. The patient was a 62-year-old
      Japanese man who died of hepatic failure and uncontrolled ascites. On autopsy, a
      large hepatic tumor was observed, which microscopically was composed of
      hepatocellular carcinoma and yolk sac tumor. The two components were
      intermingled, and transition zones were evident. Immunohistochemically, both
      components were positive for alpha-fetoprotein, but only the yolk sac tumor
      component was positive for carcinoembryonic antigen, epithelial membrane antigen,
      stage specific embryonic antigen-1, placental alkaline phosphatase, and keratin.
      To our knowledge, this is the first reported case of hepatic yolk sac tumor
      associated with hepatocellular carcinoma. The present tumor is best considered a
      variant of hepatocellular carcinoma showing yolk sac differentiation, and it
      provides another explanation for the histogenesis of extragonadal yolk sac tumor.

PMID- 8757480
TI  - Quantitative analysis of the effects of custom-molded orthoses.

PMID- 8757481
TI  - Treatment-based classification system for assessment and care of diabetic feet.
AB  - Appropriate care of feet of patients with diabetes requires a clear, descriptive
      classification system that may be used to direct appropriate therapy and possibly
      predict outcome. Ideally, this system would be used by all participants in a
      multidisciplinary limb-salvage team. The authors report on a logical, treatment
      oriented system that may improve communication, leading to a less complex, more
      predictable treatment course and, ultimately, an improved result.

PMID- 8757482
TI  - Validating the process of taking lateral foot x-rays.
AB  - This study validates the concept that a standard (static) weightbearing lateral x
      ray, taken with an orthoposer device, in the patient's angle and base of gait is
      clinically similar to findings seen during ambulatory (dynamic) gait. Sixty
      female subjects requiring diagnostic x-rays underwent videofluoroscopy of their
      walking gait. Using a single-frame, shuttle-advance video recorder, the
      appropriate fluoroscopic video frame was identified. The calcaneal pitch angle
      was measured using a digitized program. A high repeatability of the measuring
      process and high correlation between x-ray and fluoroscopic results suggest the
      value of taking weightbearing angle and base of gait lateral x-rays.

PMID- 8757483
TI  - Changes in the calcaneal pitch during stance phase of gait. A fluoroscopic
      analysis.
AB  - Calcaneal pitch has been considered to be an indirect measure of subtalar joint
      function. The aim of this pilot study was to assess changes in the calcaneal
      pitch angle during dynamic gait. Sixty female subjects underwent videofluoroscopy
      to obtain 27 usable gait cycle data. A single-frame, shuttle-advance video
      recorder was used to identify midstance of the gait cycle. The calcaneal pitch
      angle was measured during three midstance periods. The study confirms findings
      from video and forceplate analysis and reintroduces videofluoroscopy as a gait
      research tool.

PMID- 8757484
TI  - Review of the effect of fixation on complication rate in the base wedge
      osteotomy.
AB  - The complications of elevation and shortening in the oblique closing base wedge
      osteotomy of the first metatarsal fixated with either a single AO screw or two
      0.062 Kirschner wires were compared. Thirty-three consecutive oblique closing
      base wedge osteotomies of the first metatarsal bone are evaluated. With the
      exception of fixation, which is examined as an independent variable, the patients
      are managed identically with respect to osteotomy technique and postoperative
      care. The Reese osteotomy guide is used to normalize osteotomy configuration. The
      authors found no difference in elevation or shortening when comparing an AO screw
      with 0.062 Kirschner wire fixation. When other variables are controlled, fixation
      type does not lead to a statistical difference in elevation or shortening.

PMID- 8757485
TI  - Metastatic endometrial carcinoma of the foot. A case report.

PMID- 8757486
TI  - Considerations of prescription medications for the pregnant podiatric patient.
AB  - Prescription medications are thought to cause less than 1% of all congenital
      abnormalities. However, prescribing a medication to treat the foot disorder of a
      pregnant patient can be a source of anxiety for the physician. The authors review
      some of the medications commonly prescribed in podiatric medical practice and
      evaluate their use and safety during pregnancy.

PMID- 8757487
TI  - Copperhead snakebite of the foot.

PMID- 8757488
TI  - Giant cell tumor of tendon sheath.

PMID- 8757489
TI  - Shock-absorbing orthotic inserts.

PMID- 8757491
TI  - An evaluation of empirical measures of source identification.
AB  - Source identification refers to memory for the origin of information. A
      consistent nomenclature is introduced for empirical measures of source
      identification which are then mathematically analyzed and evaluated. The ability
      of the measures to assess source identification independently of identification
      of an item as old or new depends on assumptions made about how inconsistencies
      between the item and source components of a source-monitoring task may be
      resolved. In most circumstances, the empirical measure that is used most often
      when source identification is measured by collapsing across pairs of sources
      (sometimes called "the identification-of-origin score") confounds item
      identification with source identification. Alternative empirical measures are
      identified that do not confound item and source identification in specified
      circumstances. None of the empirical measures examined provides a valid measure
      of source identification in all circumstances.

PMID- 8757490
TI  - Feature memory and binding in young and older adults.
AB  - Intact memory for complex events requires not only memory for particular features
      (e.g., item, location, color, size), but also intact cognitive processes for
      binding the features together. Binding provides the memorial experience that
      certain features belong together. The experiments presented here were designed to
      explicate these as potentially separable sources of age-associated changes in
      complex memory-namely, to investigate the possibility that age-related changes in
      memory for complex events arise from deficits in (1) memory for the kinds of
      information that comprise complex memories, (2) the processes necessary for
      binding this information into complex memories, or (3) both of these components.
      Young and older adults were presented with colored items located within an array.
      Relative to young adults, older adults had a specific and disproportionate
      deficit in recognition memory for location, but not for item or for color. Also,
      older adults consistently demonstrated poorer recognition memory for bound
      information, especially when all features were acquired intentionally. These
      feature and binding deficits separately contribute to what have been described as
      older adults' context and source memory impairments.

PMID- 8757492
TI  - Perceptual and conceptual priming in a semantic reprocessing task.
AB  - Two experiments are reported that addressed the relative involvement and nature
      of perceptual and conceptual priming in a semantically complex task. Both
      experiments investigated facilitation from repeated semantic comparison trials in
      which subjects decided whether two words had the same meaning (e.g., moist damp).
      The first experiment compared the magnitude and persistence of perceptual and
      conceptual priming components. Perceptual priming effects were modest, and
      contrary to some previous evidence, they did not appear to be more persistent
      than nonperceptual priming effects. The second experiment investigated the memory
      processes involved when perceptual priming was eliminated through a modality
      change between prime and target trials. Evidence suggested that conceptual
      priming primarily involved memory for the meaning comparison processes rather
      than better access to existing memory for the stimulus words.

PMID- 8757493
TI  - Size and reflection effects in priming: a test of transfer-appropriate
      processing.
AB  - Prior research has suggested that priming on perceptual implicit tests is
      insensitive to changes in stimulus size and reflection. The present experiments
      were performed to investigate whether size and reflection effects can be obtained
      in priming under conditions that encourage the processing of this information at
      study and at test, as predicted by transfer-appropriate processing. The results
      indicate that priming was affected by a change in the physical size of an object
      when study and test tasks required a judgment about the real size of pictorial
      objects (e.g., deciding whether a zebra presented small or large on the screen
      was larger or smaller than a typical chair), and when the test task required the
      identification of fragmented pictures. However, a change in left-right
      orientation had no effect on priming when study and test tasks required a
      judgment about the left-right orientation of familiar objects, or when the test
      task involved the identification of fragmented pictures. This difference between
      size and reflection effects is discussed in terms of the differential importance
      of size and reflection information in shape identification.

PMID- 8757494
TI  - Divided attention and indirect memory tests.
AB  - Attentional state during acquisition is an important determinant of performance
      on direct memory tests. In two experiments we investigated the effects of
      dividing attention during acquisition on conceptually driven and data-driven
      indirect memory tests. Subjects read a list of words with or without distraction.
      Memory for the words was later tested with an indirect memory test or a direct
      memory test that differed only in task instructions. In Experiment 1, the
      indirect test was category-exemplar production (a conceptually driven task) and
      the direct test was category-cued recall. In Experiment 2, the indirect test was
      word-fragment completion (a data-driven task) and the direct test was word
      fragment cued recall. Dividing attention at encoding decreased performance on
      both direct memory tests. Of the indirect tests, category-exemplar production but
      not word-fragment completion was affected. The results indicate that conceptually
      driven indirect memory tests, like direct memory tests, are affected by divided
      attention, whereas data-driven indirect tests are not. These results are
      interpreted within the transfer-appropriate processing framework.

PMID- 8757495
TI  - Compound word effects differ in reading, on-line naming, and delayed naming
      tasks.
AB  - Bimorphemic compound words (e.g., blueberry), bimorphemic suffixed words (e.g.,
      ceaseless), and monomorphemic controls (e.g., arthritis) were read in neutral
      sentence contexts in Experiment 1. The main result revealed longer first fixation
      durations on compound words than on control and suffixed words. Different effects
      emerged when naming tasks were used. An on-line naming task revealed
      substantially shorter naming latencies for compound words than for control and
      suffixed words. Naming latencies for compound and control words were equivalent
      in a delayed naming task. These results indicate that on-line naming latencies
      and word-viewing durations may yield diverging results. They also suggest that
      activation of constituent words of compound words occurs independently from the
      specification of conventional word meanings.

PMID- 8757496
TI  - The influence of lexical and conceptual constraints on reading mixed-language
      sentences: evidence from eye fixations and naming times.
AB  - In two experiments, we explored the degree to which sentence context effects
      operate at a lexical or conceptual level by examining the processing of mixed
      language sentences by fluent Spanish-English bilinguals. In Experiment 1,
      subjects' eye movements were monitored while they read English sentences in which
      sentence constraint, word frequency, and language of target word were
      manipulated. A frequency x constraint interaction was found when target words
      appeared in Spanish, but not in English. First fixation durations were longer for
      high-frequency Spanish words when these were embedded in high-constraint
      sentences than in low-constraint sentences. This result suggests that the
      conceptual restrictions produced by the sentence context were met, but that the
      lexical restrictions were not. The same result did not occur for low-frequency
      Spanish words, presumably because the slower access of low-frequency words
      provided more processing time for the resolution of this conflict. Similar
      results were found in Experiment 2 using rapid serial visual presentation when
      subjects named the target words aloud. It appears that sentence context effects
      are influenced by both semantic/conceptual and lexical information.

PMID- 8757497
TI  - Recall of random and distorted chess positions: implications for the theory of
      expertise.
AB  - This paper explores the question, important to the theory of expert performance,
      of the nature and number of chunks that chess experts hold in memory. It examines
      how memory contents determine players' abilities to reconstruct (1) positions
      from games, (2) positions distorted in various ways, and (3) random positions.
      Comparison of a computer simulation with a human experiment supports the usual
      estimate that chess Masters store some 50,000 chunks in memory. The observed
      impairment of recall when positions are modified by mirror image reflection
      implies that each chunk represents a specific pattern of pieces in specific
      location. A good account of the results of the experiments is given by the
      template theory proposed by Gobet and Simon (in press) as an extension of Chase
      and Simon's (1973b) initial chunking proposal, and in agreement with other recent
      proposals for modification of the chunking theory (Richman, Staszewski, & Simon,
      1995) as applied to various recall tasks.

PMID- 8757498
TI  - Sex differences in visuospatial ability: do performance factors play such an
      important role?
AB  - This study was designed to analyze some performance factors as a possible source
      of sex-related bias in psychometric tests of visuospatial aptitude. Goldstein,
      Haldane, and Mitchell (1990) explored the effect of two response styles-slowness
      of performance and reluctance to guess-by using a 3-D mental rotation test (the
      task showing the largest cognitive sex difference) and found that time limits and
      raw scores contributed substantially to the male advantage. We applied two tests
      in the speed-power continuum to a representative sample of 621 males and 821
      females in their last year of high school in a 2 x 2 (gender x time) full
      factorial design. Reluctance to guess was similar for males and females. Males
      obtained more correct responses on both tests, and for both time conditions, than
      did females. These results are not only statistically significant but also are of
      substantial practical consequence.

PMID- 8757499
TI  - Causal order does not affect cue selection in human associative learning.
AB  - Waldmann and Holyoak (1992) presented evidence in support of the claim that cue
      selection does not emerge in "diagnostic" human learning tasks in which the cues
      are interpretable as effects and the outcomes as the causes of those effects.
      Waldmann and Holyoak argued that this evidence presents a major difficulty for
      associationist theories of learning and instead supports a "causal model" theory.
      We identify a number of flaws in Waldmann and Holyoak's experimental procedures
      and report three new experiments designed to test their claim. In Experiment 1,
      cue selection was observed regardless of causal order and regardless of whether
      the cues were abstractly or concretely specified. In Experiments 2 and 3, cue
      selection was again observed when subjects predicted causes from effects. We
      conclude that our results are consistent with simple associationist theories of
      learning but contradict Waldmann and Holyoak's causal model theory.

PMID- 8757500
TI  - The role of decision processes in remembering and knowing.
AB  - Participants in recognition memory studies are now often asked to partition
      recognized items into ones that are accompanied by some recollective experience
      (those they remember) and ones that are not so accompanied (but which they know
      were previously encountered). Rather than detecting separate memory systems, such
      attempts to distinguish between remembering and knowing are better understood as
      a division of positive recognition responses into those that lie above a second
      decision criterion (remember) and those that do not (know). As such, the amount
      of memory associated with knowing is strongly dependent on the placement of the
      decision criteria. A meta-analysis of published data and a simple experiment
      tested predictions from the decision process analysis of remember/know responses.

PMID- 8757501
TI  - Estimation of the number of mutations necessary to cause chronic myeloid
      leukaemia from epidemiological data.

PMID- 8757502
TI  - Interaction of the receptor tyrosine kinase p145c-kit with the p210bcr/abl kinase
      in myeloid cells.
AB  - The chimaeric bcr/abl oncogene is detected in virtually all cases of chronic
      myelogenous leukaemia (CML). It encodes a constitutively active tyrosine kinase
      of 210 kDalton, p210bcr/abl, which stimulates a variety of cytosolic signalling
      intermediates. The effects of bcr/abl on the activity of growth factor receptors
      are less well known. In order to investigate interaction of p210bcr/abl with the
      receptor tyrosine kinase p145c-kit, we used two myeloid, factor-dependent cell
      lines, MO7 and 32D, to generate bcr/abl positive sublines, MO7p210 and 32Dp210,
      by transfection with the bcr/abl gene. Since 32D and 32Dp210 cells did not
      express p145c-kit, a c-kit retrovirus was used to generate c-kit positive cell
      lines (32Dkit, 32Dp210kit). In contrast to MO7 and 32Dkit cells, MO7p210 and
      32Dp210kit cells were factor independent and did not respond to the growth
      promoting effects of recombinant human Steel factor (rhSF). Preincubation with a
      monoclonal antibody (MAb) neutralizing the binding of SF to p145c-kit did not
      affect the growth of MO7p210 cells, thus eliminating the possibility of an
      autocrine SF secretion. 32Dkit cells transfected with bcr/abl containing an
      inactivating point mutation (Lys-->Arg271) in the Abl kinase domain
      (32Dp210(Arg271)kit) retained their responsiveness to the effects of rhSF. Immune
      complex kinase assays showed that the kinase activity of p145c-kit was several
      fold higher in MO7p210 and 32Dp210kit cells than in MO7, 32Dkit and
      32Dp210(Arg271)kit cells, suggesting that Abl kinase activity was necessary to
      activate p145c-kit. Co-immunoprecipitation experiments with anti-Kit and anti-Abl
      MAbs demonstrated that p145c-kit and p210bcr/abl were associated in an
      intracellular complex in human bcr/abl positive, c-kit positive cell lines
      (MO7p210; GM/SO). Finally, colony assays with bone marrow from bcr/abl positive
      CML patients showed that the haemopoietic progenitors of three of four patients
      did not respond to rhSF. Taken together, the results suggest that p145c-kit can
      be activated by p210bcr/abl via an Abl-kinase dependent mechanism involving the
      complex formation of both proteins. These findings could explain some clinical
      features (basophilia, increase of immature myeloid cells) of chronic-phase CML.

PMID- 8757503
TI  - Regulation of colony forming cell generation by flt-3 ligand.
AB  - The recently cloned ligand for the flt-3/flk-2 receptor was examined for its
      effect on colony formation by subpopulations of CD34+ cells including the least
      mature CD34+lin-CD38- small-medium lymphocyte-sized cell population. Flt-3 ligand
      (flt-3l) had little or no effect when added alone to cells. Isolated CD34+lin+
      cells formed increased numbers of colony-forming cells (CFC) when flt-3l was
      added together with IL-3, IL-6, G-CSF, GM-CSF or c-kit ligand (KL), or with the
      combination of IL-3 and KL. Significant increases in CFC formation from CD34+lin-
      cells were consistently seen when flt-3l was added to the IL-3 and KL
      combination, with variable effects observed when it was added to individual
      growth factors. Studies of the generation of CFC from CD34+lin- cells in liquid
      cultures showed that cultures containing IL-3 and KL continued to produce CFC
      after 3 weeks of culture, whereas cultures with IL-3, KL and flt-3l produced few
      CFC past 2 weeks of culture. Flt-3l alone or the combination of IL-3 and KL did
      not stimulate significant growth of CD34+lin-CD38- small-medium lymphocyte-sized
      cells, although these cells reproducibly generated CFC when grown in the
      combination of IL-1 beta, IL-3, IL-6, G-CSF, GM-CSF and KL. Addition of flt-3l to
      either IL-3 and KL or to a combination of growth factors induced increased CFC in
      three of four experiments. These data therefore demonstrate a role for flt-3l in
      the induction of myelopoiesis by haemopoietic precursors, including the least
      mature subpopulation population of CD34+ cells.

PMID- 8757504
TI  - Expression of the multidrug resistance-associated protein (MRP) mRNA and protein
      in normal peripheral blood and bone marrow haemopoietic cells.
AB  - We studied the expression of multidrug resistance-associated protein (MRP) in
      normal haemopoietic cells from peripheral blood and bone marrow. The MRP mRNA
      levels were estimated by RT/PCR and in situ hybridization (ISH) assay, and the
      protein levels by flow cytometry. 21 samples of peripheral blood and 21 samples
      of bone marrow (11 normal bone marrow donors, 10 patients in complete remission
      after chemotherapy for large cell lymphoma or acute myeloid leukaemia) were
      analysed. In peripheral blood the mean MRP mRNA level in CD3+ cells was
      statistically higher than in the other cells (3-fold by the methods used). The
      levels of MRP in CD3+ varied from one individual to another (4.5-34.8 units by
      RT/PCR and 5-23 grains/cell by ISH); however, this was proportional to the
      variation in all the cell lineages of same individual (r = 0.84). In bone marrow
      the mean MRP levels of the various cell lineages (including CD34+) were similar
      to the basal level in HL60 cells. Individual expression levels were again
      variable; however, there was no difference between untreated normal bone marrow
      and post chemotherapy normal bone marrow. MRP protein expression was determined
      by flow cytometry with the monoclonal antibody MRPm6. The CD4+ lymphocytes
      exhibited a higher MRP protein expression than the other cell lineages, including
      CD8+ cells. There was a good correlation between the three methods used (RT/PCR
      and ISH, P = 0.0001, r = 0.87; RT/PCR and flow cytometry, P = 0.0001, r = 0.85;
      ISH and flow cytometry, P = 0.002, r = 0.67).

PMID- 8757505
TI  - A role of GAGs in ECM on morphogenesis of megakaryocytes.
AB  - The morphogenesis of megakaryocytes that results in the formation of cytoplasmic
      processes is thought to be the final maturation step before liberation of
      platelets. We studied the in vitro effects of glycosaminoglycans (GAGs) which are
      abundant in the bone marrow extracellular matrices, on the morphogenesis of
      murine megakaryocytes and compared them with those of thrombopoietic cytokines.
      Heparin, heparan sulfate, chondroitin-6 sulfate, and dermatan sulfate promoted
      the formation of megakaryocytic processes. Hyaluronic acid failed to support this
      phenomenon, suggesting that sulfated GAGs in extracellular matrices are involved
      in the morphogenesis of megakaryocytes. Sulfated GAGs began to act on
      megakaryocytes with a higher ploidy (16N-32N) from 6 to 24h after incubation,
      whereas neither rhIL-6 nor rhIL-11 affected this early phase. Our findings
      indicate that sulfated GAGs promote the morphogenesis of murine megakaryocytes
      and participate in thrombopoiesis in a different manner from that of cytokines
      such as rhIL-6 and rhIL-11.

PMID- 8757506
TI  - Granulocyte colony-stimulating factor (G-CSF) increases neutrophil migration
      across vascular endothelium independent of an effect on adhesion: comparison with
      granulocyte-macrophage colony-stimulating factor (GM-CSF).
AB  - Granulocyte colony-stimulating factor (G-CSF) increases neutrophil counts, and
      enhances and primes many neutrophil functions, implicating a role for this growth
      factor in host defence. This study investigated whether G-CSF is able to directly
      influence the transendothelial migration of neutrophils, and how such effects
      might be related to other effects on neutrophil adhesive properties. G-CSF, like
      GM-CSF, increased surface levels of the adhesive receptor, CD11b/CD18, but down
      regulated L-selectin expression on neutrophils. Unlike GM-CSF, however, G-CSF had
      no effect on neutrophil adhesion to endothelium. Despite the lack of effect on
      neutrophil adhesion, G-CSF was able to produce significant enhancement of
      neutrophil transmigration across unstimulated endothelium in vitro. When used at
      an optimal concentration of 100 ng/ml, G-CSF increased neutrophil migration to
      217 +/- 19% of baseline levels (P < 0.001, n = 10). This effect was similar to
      that previously demonstrated for GM-CSF (which increased migration to 271 +/-
      40%, P < 0.001, n = 12). G-CSF-induced transmigration, like GM-CSF induced
      migration, was independent of concentration gradients, suggesting that these are
      not simply chemotactic effects. G-CSF differs from GM-CSF, however, in that
      although GM-CSF inhibited neutrophil migration across IL-1-activated endothelium
      (33 +/- 8% inhibition, n = 6, P < 0.01), G-CSF had no effect on neutrophil
      migration across IL-1 activated endothelium. Hence G-CSF, despite having no
      effect on neutrophil adhesion to endothelium, is a powerful stimulator of
      transmigration, and, unlike GM-CSF, does not inhibit cell movement across
      inflamed endothelium. These results suggest that G-CSF is able to influence
      neutrophil recruitment into local infective sites, and, further, that G-CSF
      mobilized cells would be competent to migrate into tissues in response to
      inflammatory stimuli.

PMID- 8757507
TI  - Heparin induces apoptosis in human peripheral blood neutrophils.
AB  - Programmed cell death, by apoptosis, has been shown to play an important role in
      the regulation of haemopoiesis. Using trypan blue exclusion for distinguishing
      intact membranes, flow cytometry for detection of sub G1 peak and in situ
      terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL),
      this study shows that heparin induces apoptosis in vitro in human peripheral
      blood neutrophils. The known anti-proliferative effect of heparin in several in
      vitro cell systems has therefore to be interpreted in the light of apoptosis. In
      addition, apoptosis may help explain the anti-inflammatory effects resulting from
      the interaction between vessel wall heparan sulphate and chemoattracted
      peripheral blood neutrophils.

PMID- 8757508
TI  - Interleukin-6 is required for pristane-induced plasma cell hyperplasia in mice.
AB  - Intraperitoneal injection of pristane induces production of interleukin-6 (IL-6)
      and either plasmacytosis or plasmacytoma in mice, depending upon the genetic
      background. Pristane does not induce plasmacytoma in IL-6 knockout (IL-6-/-)
      mice, suggesting that IL-6 is required for this process. In the present study we
      determined whether IL-6 is also required for pristane-induced hyperplasia of
      normal plasma cells. Pristane was injected intraperitoneally into IL-6-/- and IL
      6 wild-type (IL-6+/+) mice. Overall there were more deaths in IL-6+/+ mice (85%)
      than in IL-6-/- mice (40%), P = 0.024. Hyperplastic lymph node and spleen weight
      did not differ (P = 0.82 and P = 0.15, respectively) in IL-6-/- versus IL-6+/+
      mice. Lymphocytosis with similar patterns of expression of B-cell (B220) and T
      cell (Thy-1) antigens was noted in both IL-6-/- and IL-6+/+ mice. However,
      morphological studies, dual fluorescent staining for Syn-1 and B220 antigens (syn
      1+ B220+ cells), and intracytoplasmic Ig staining revealed plasma cell
      hyperplasia in lymph node and spleen from IL-6+/+, but not IL-6-/-, mice. These
      plasma cells from IL-6+/+ mice were polyclonal and unable to induce tumour
      formation in severe combined immunodeficient mice. These data demonstrate that IL
      6 is required for pristane-induced hyperplasia of polyclonal plasma cells in
      mice.

PMID- 8757509
TI  - Clonal expansion of gamma delta T cells expressing two distinct T-cell receptors.
AB  - 92% of peripheral blood mononuclear cells from a patient with chronic
      lymphocytosis (WBC 22 x 10(9)/l) were recognized by pan-gamma delta monoclonal
      antibody (mAb) TCR delta 1. Further analysis with anti-V gamma/V delta mAb
      indicated that the expanded gamma delta T-cell population was stained by mAb
      specific for V gamma 2/3/4, V gamma 5 and V delta 1 but not mAb specific for V
      gamma 8, V gamma 9, V delta 2 or V delta 3. Cloning and sequencing of reverse
      transcription PCR products revealed the presence of V gamma 4, V gamma 5 and V
      delta 1 in-frame transcripts. All the cDNA clones obtained from each of these
      variable elements had identical junction regions, thus clearly demonstrating
      clonality. As far as we know, this is the first description of a pathological
      clonal expansion of gamma delta T cells with two distinct surface-expressed T
      cell receptor molecules.

PMID- 8757510
TI  - Unrelated donor bone marrow transplantation to treat severe aplastic anaemia in
      children and young adults.
AB  - Alternative donor bone marrow transplantation (BMT) to treat severe aplastic
      anaemia (SAA) in children and young adults has been complicated by high rates of
      graft rejection and severe graft-versus-host disease (GVHD). We hypothesized that
      increased immunosuppression combined with T-cell depletion of the marrow graft
      would enable successful use of unrelated donor BMT in this disease.
      Preconditioning consisted of cytosine arabinoside, cyclophosphamide, and total
      body irradiation (TBI). T-cell depletion was with the anti-CD3 antibody T10B9.
      GVHD prophylaxis consisted of cyclosporine A. 28 previously transfused patients
      were transplanted. Nine donor/recipient pairs were HLA matched. As of 1 January
      1996, 15/28 (54%) patients are alive, transfusion independent and well with a
      range of follow-up of 13 months to 8 years (median 2.75 years). Fatalities
      include all three patients with nonengraftment and all three patients with grade
      III/IV GVHD. Other fatalities were due to infections or therapy-related toxicity.
      The incidence >or= grade II acute GVHD was 28%. These data show that in children
      with SAA who have failed immunosuppression, unrelated donor BMT offers a
      reasonable hope of long-term survival.

PMID- 8757511
TI  - Flutamide-induced cyanosis refractory to methylene blue therapy.
AB  - Flutamide, an anti-androgen used in prostate cancer therapy, is also a derivative
      of aniline. Mild, usually asymptomatic, methaemoglobinaemia has been reported. We
      report a patient receiving flutamide therapy who developed cyanosis, dyspnoea and
      anaemia, initially attributed to marked methaemoglobinaemia by the CO-Oximeter
      method. An unsuccessful trial of methylene blue therapy led to the finding of
      marked sulphaemoglobinaemia. Sulphaemoglobinaemia has not previously been
      reported with flutamide use. Recognition of this association is important, given
      the refractoriness of sulphaemoglobinaemia to methylene blue therapy.

PMID- 8757512
TI  - The labelling index of primitive plasma cells determines the clinical behaviour
      of patients with myelomatosis.
AB  - For patients with multiple myeloma the most important laboratory correlate of
      prognosis and disease activity is the bromodeoxyuridine (BrdUrd) plasma cell
      labelling index (LI). However, the traditional immunofluorescent microscope LI
      technique, like other manual enumeration assays, can suffer from poor precision
      and accuracy. In this study the LI of different subpopulations of plasma cells
      (CD38++) as determined by flow cytometry was correlated with disease state. The
      mean LI of the total CD38++ population was significantly higher (2.7 +/- 0.4%)
      than the LI determined by the traditional slide technique (0.6 +/- 0.1%) for 65
      samples tested. Primitive plasma cells (CD38++, CD45++) had a higher labelling
      index than mature plasma cells (CD38++, CD45-) (7.0 +/- 1.3% v 1.8% +/- 0.3%) and
      in one patient the LI of the primitive plasma cells was 46%. In addition, the LI
      of the mature plasma cells was lower than the total plasma cell population. As
      expected, there was a significant difference between the LI of patients in
      plateau phase and progressive disease but this difference was greatest when the
      LI of the primitive plasma cells was studied (9.2 +/- 2.9% v 2.2 +/- 0.7%; z =
      19.9, P < 0.001). This study has raised some concerns about the sensitivity and
      accuracy of the traditional labelling index and has shown that the increased LI
      associated with progressive disease is almost entirely attributable to an
      increase in the LI of the primitive plasma cell subpopulation and that the LI of
      primitive plasma cells provides a more clinically significant correlation with
      disease status than the traditional assay.

PMID- 8757513
TI  - A population-based study of 272 children with acute myeloid leukaemia treated on
      two consecutive protocols with different intensity: best outcome in girls,
      infants, and children with Down's syndrome. Nordic Society of Paediatric
      Haematology and Oncology (NOPHO).
AB  - From July 1984 the five Nordic countries (Denmark, Finland, Iceland, Norway and
      Sweden) have registered all children with acute myeloid leukaemia (AML) and
      treated them on two consecutive protocols of different intensity (NOPHO-84 and
      NOPHO-88). We probably have information on every child with this diagnosis in our
      region. We found an annual incidence of AML of 0.7 new cases per 100,000 children
      < 16 years of age. We observed a distinct peak of incidence in the first 2 years
      of life. Children with Down's syndrome accounted for 13% of all cases. Eighty of
      105 cases treated on NOPHO-84 achieved remission (78%). In NOPHO-88, 100/118
      patients entered remission (85%). The overall event-free survival (p-EFS) for the
      two studies was 0.32 for NOPHO-84 and 0.42 for NOPHO-88. The majority of relapses
      occurred within 2 years of diagnosis. When looking for prognostic factors the
      strongest significant adverse factor found was male sex. Children with Down's
      syndrome (n = 35) had a very favourable outcome if they received therapy
      according to protocol, and infants (n = 26) had a superior outcome compared to
      children 1-2 years or > 10 years of age at diagnosis.

PMID- 8757514
TI  - Dose intensification in acute myeloid leukaemia: greater effectiveness at lower
      cost. Principal report of the Medical Research Council's AML9 study. MRC
      Leukaemia in Adults Working Party.
AB  - Between 1984 and 1990, 972 patients aged 1-79 years with acute myeloid leukaemia
      (AML), from 85 British hospitals, were entered into the MRC's 9th AML trial.
      Patients were randomized between DAT 1 + 5 (daunorubicin for 1 d, with cytarabine
      and 6-thioguanine for 5 d) and DAT 3 + 10 (same dose drugs for 3 and 10 d
      respectively) as induction therapy. The 63% who achieved complete remission (CR)
      were randomized to receive two courses of DAT 2 + 7 alternating with two courses
      of either MAZE (m-AMSA, 5-azacytidine, etoposide) or COAP (cyclophosphamide,
      vincristine, cytarabine, prednisone). Finally, those still in CR were randomized
      to receive either 1 year of maintenance treatment with eight courses of
      cytarabine and thioguanine followed by four courses of COAP, or no further
      cytotoxic therapy. Resistance to induction therapy was less common with the DAT 3
      + 10 regimen than with DAT 1 + 5 (13% v 23%; P = 0.0001) and hence, despite a 5%
      increase in the risk of induction death, the CR rate was higher (66% v 61%; P =
      0.15). Moreover, CR was achieved more rapidly with DAT 3 + 10 (median 34 v 46 d;
      P < 0.0001) and thus patients required less time in hospital (mean 20 v 29 d) and
      less blood product support. 5-year relapse-free survival (28% v 23%; P = 0.05)
      and survival (23% v 18%; P < 0.05) were also better with DAT 3 + 10. Post
      remission intensification of therapy with MAZE resulted in fewer relapses (66% v
      74% at 5 years; P = 0.03) but patients allocated MAZE required considerably more
      supportive care and 14 (4.5%) died following 312 MAZE courses, whereas no deaths
      occurred following COAP. 5-year survival was not significantly higher with MAZE
      (37% v 31%). Finally, although 1 year of outpatient maintenance treatment
      appeared to delay, but not prevent, recurrence it did not improve 5-year survival
      which was non-significantly worse for those allocated maintenance treatment (41%
      v 44%). We conclude that the more intensive induction regimen, DAT 3 + 10, is not
      only more effective than DAT 1 + 5, even for older patients, but is also less
      expensive; intensive post-remission therapy with MAZE achieves better leukaemic
      control but at the cost of substantial toxicity; whereas low-level maintenance
      therapy confers no apparent advantage in survival as well as being inconvenient
      and costly.

PMID- 8757515
TI  - Expression and prognostic value of the retinoblastoma tumour suppressor gene (RB
      1) in childhood acute lymphoblastic leukaemia.
AB  - In a retrospective analysis, acute lymphoblastic leukaemia (ALL) blast cells of
      102 children were investigated for the expression of the retinoblastoma
      susceptibility (RB)-1 gene at mRNA level by dot blot hybridization and
      semiquantitative RT-PCR. 56 patients were analysed by dot blot hybridization and
      35 representative patients out of this group by semiquantitative RT-PCR. Two
      additional groups of patients (23 patients with initial and 23 patients with
      relapsed ALL) were also investigated by semiquantitative RT-PCR. RB-1 gene
      expression was detectable in all investigated ALL at different levels. According
      to the relative mRNA expression the patients were discriminated by the median
      value in groups with low or high RB-1 expression. The Kaplan-Meier estimates
      showed that patients with low RB-1 expression had a lower probability of
      remaining in first remission (P = 0.03) and a significantly higher risk to
      succumb to their disease (P = 0.03). Furthermore, the comparison of the results
      between initial and relapsed ALL showed that the relapses had significantly lower
      RB-1 mRNA expression (P = 0.02). The overall survival of the patients was shorter
      in both groups when RB-1 gene expression was low. A multivariate analysis,
      including age, sex, immunological subtype, initial white blood cell count and RB
      1 expression, identified RB-1 as an independent prognostic predictor (P = 0.017)
      in addition to the initial white blood cell count (P = 0.00001). In conclusion,
      low RB-1 expression is an unfavourable prognostic predictor in initial and
      relapsed childhood ALL. The RB-1 gene expression in relapsed ALL is significantly
      lower than in initial ALL.

PMID- 8757516
TI  - The der(21)t(12;21) chromosome is always formed in a 12;21 translocation
      associated with childhood acute lymphoblastic leukaemia.
AB  - We studied 116 patients (93 children and 23 adults) with acute lymphoblastic
      leukaemia (ALL) using fluorescence in situ hybridization (FISH) with the yeast
      artificial chromosome (YAC) clone, 964c10, which includes the recently described
      ETS-like gene, TEL, on 12p13. FISH revealed that nine of the patients had a
      t(12;21), which had not been previously detected. The nine patients were all
      children, seven boys and two girls, aged 1-10 years (median 3 years), had an
      early B immunophenotype, and achieved complete remission, although two of them
      experienced haematological relapse. In addition to the t(12;21), FISH also
      revealed that three of the nine had a del(12p) in the other homolog of chromosome
      12 or in the der(12) chromosome itself, and that two others had 12p
      translocations in the other chromosome 12 homolog. Although chromosomal
      rearrangements associated with the t(12;21) were heterogenous and complex, fusion
      of the sequences from chromosomes 12 and 21 on the der(21)t(12;21) chromosomes
      was consistent, suggesting that the TEL-AML1 gene fusion on the der(21)
      chromosome may be critical in leukaemogenesis and that FISH or reverse
      transcriptase-polymerase chain reaction (RT-PCR) targeted to the chimaeric
      sequences on the der(21) will be most useful in detecting the t(12;21) or
      following a patient with the t(12;21), which is one of the most frequent
      chromosomal rearrangements in both Caucasian and Asian childhood ALL.

PMID- 8757517
TI  - Low incidence of specific anti-platelet antibodies detected by the MAIPA assay in
      the serum of thrombocytopenic MDS patients and lack of correlation between
      platelet autoantibodies, platelet lifespan and response to danazol therapy.
AB  - We prospectively studied the mechanism of thrombocytopenia in 30 patients with
      myelodysplastic syndrome (MDS), who had a platelet count <or= 70 x 10(9)/l, and
      marrows blasts <or= 10% by analysis of platelet lifespan, platelet-bound IgG
      antibodies by platelet radioactive antiglobulin test (PRAT), and circulating and
      platelet-bound autoantibodies specifically directed against platelet
      glycoproteins by indirect and direct MAIPA test. PRAT analysis was positive in
      21/30 patients (70%), but antiplatelet antibodies were found in only eight by the
      MAIPA test. Platelet lifespan was shortened in five cases, only one of whom had a
      positive MAIPA test. Patients were treated by danazol (600 mg/d), and 9/26
      evaluable patients (35%) responded, including three of the five patients with
      shortened platelet lifespan. No correlation between platelet lifespan, results of
      PRAT and MAIPA tests, and response to danazol was found. In conclusion, specific
      antiplatelet autoantibodies, reduced platelet lifespan, and efficacy of androgen
      therapy on platelets were seen in 20%, 17% and 35% of MDS with thrombocytopenia,
      respectively, but no correlation between these findings was found in this study.

PMID- 8757518
TI  - Prognostic factors in myelodysplastic syndromes: critical analysis of the impact
      of age and gender and failure to identify a very-low-risk group using standard
      mortality ratio techniques.
AB  - We studied the prognostic value of age and gender by survival, and by standard
      mortality ratio (SMR) analyses, in 203 untreated patients with myelodysplastic
      syndromes (MDS); 57 refractory anaemia (RA), 23 refractory anaemia with ringed
      sideroblasts, 41 refractory anaemia with excess blasts (RAEB), 3 RAEB in
      transformation (RAEB-T) and 79 chronic myelomonocytic leukaemia (CMML), aged 23
      89 years (median 69, M/F 0.5), who were all karyotyped. Median survival was 36
      months. Adverse prognostic factors were: high bone-marrow blast percentage,
      complex karyotype, low platelet count, age > 60 years, low or high WBC count,
      haemoglobin < 10 g/dl, male gender. However, the standard mortality ratio (i.e.
      mortality compared to that of an age- and sex-adjusted population) was not
      different between male and female patients. Patients < 60 had a higher SMR than
      older patients. Therefore the prognostic values of age and gender for survival in
      MDS patients may reflect, at least in part, a characteristic of the population.
      Furthermore, even in low-risk groups defined by scoring system we were unable to
      define a subgroup of patients with a mortality similar to that of the normal
      population, especially in MDS patients aged < 60.

PMID- 8757519
TI  - Graft failure after donor leucocyte infusion in relapsed chronic myeloid
      leukaemia: successful treatment with cyclophosphamide and antithymocyte globulin
      followed by peripheral blood stem cell infusion.
AB  - We report a patient with chronic myeloid leukaemia who underwent allogeneic
      marrow transplantation (BMT) but had a molecular relapse 5 months and
      haematological relapse 15 months after BMT. Since therapy with alpha-interferon
      had been ineffective he received leucocyte infusions from his sibling donor. He
      developed acute graft-versus-host disease and became aplastic 6 weeks later.
      Despite donor marrow infusion and cytokine stimulation marrow aplasia persisted
      for 13 weeks. Then, donors' peripheral blood stem cells were given after
      conditioning with cyclophosphamide and antithymocyte globulin resulting in
      trilineage engraftment of donor haemopoiesis. Since then, the patient has been in
      continuous molecular remission for 11 months.

PMID- 8757520
TI  - Second transplantation with CD34+ bone marrow cells selected from a two-loci HLA
      mismatched sibling for a patient with chronic myeloid leukaemia.
AB  - A 43-year-old man with chronic myeloid leukaemia underwent a second transplant
      with CD34+ bone marrow cells selected from his two-loci HLA-mismatched sibling
      after rejection of the first graft from an HLA-matched unrelated donor. By
      immunomagnetic positive selection, CD34+ marrow cells at 0.95 x 10(6)/kg with 97%
      purity and CD3+ T lymphocytes at 1.3 x 10(4)/kg were collected and transplanted.
      Engraftment was confirmed to be of CD34+ cell-donor origin. The patient developed
      only grade I acute graft-versus-host disease (GVHD) and no chronic GVHD to date.
      These observations suggest that allogeneic CD34+ bone marrow cells are capable of
      reconstituting haemopoiesis and that CD34+ selection could be applicable to T
      cell depletion.

PMID- 8757521
TI  - Fanconi's anaemia presenting as acute myeloid leukaemia in adulthood.
AB  - We describe a 28-year-old male patient who presented with apparently de novo
      acute myeloid leukaemia (AML) who was subsequently found to have Fanconi's
      anaemia (FA). The gene for complementation group A (FAA) has recently been
      localized to chromosome 16q24.3 and utilizing genetic markers closely linked to
      this locus we were able to conclude that this patient was likely to belong to
      complementation group A. FA presenting as AML is an exceptionally rare event and
      all previously described cases have occurred in patients less than 21 years of
      age. We conclude that the diagnosis of FA should always be considered in younger
      patients presenting with AML. It is important that the correct diagnosis is made
      in these individuals because the administration of conventional chemotherapy may
      well have devastating consequences for them. Correlations between the specific
      mutations causing FA and clinical phenotypes are likely to become apparent as
      more genetic analyses are performed in this group of patients.

PMID- 8757522
TI  - GM-CSF raises serum levels of beta 2-microglobulin and thymidine kinase in
      patients with chronic lymphocytic leukaemia.
AB  - The effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on
      biochemical tumour markers beta 2-microglobulin (beta 2m), thymidine kinase (TK)
      and lactate dehydrogenase (LDH) were studied in eight patients with chronic
      lymphocytic leukaemia (CLL). The serum concentration of beta 2m rose by a median
      of 30% (range 8-50%) and serum TK by 101% (range 30-1414%). Serum LDH
      concentration, on the other hand, significantly decreased in all patients. The
      significant increases of beta 2m and TK could not be explained by progression of
      the disease or impaired renal function. Treatment with GM-CSF reduces the value
      of serum beta 2m and TK in assessment of tumour mass and disease activity.

PMID- 8757523
TI  - A case of mature B-cell ALL with coexistence of t(1;19) and t(14;18) and
      expression of the E2A/PBX1 fusion gene.
AB  - The translocation t(1;19)(q23;p13) is found in 3-5% of all acute lymphoblastic
      leukaemias (ALL) and results in the expression of an E2A/PBX1 hybrid gene
      transcript. This translocation is very closely associated with a pre-B phenotype.
      t(14;18) is associated with follicular B-cell lymphoma and is characterized by
      over-expression of the bcl-2 oncogene. We describe a case of ALL in an adult with
      a mature B-cell immunophenotype and a single abnormal cell line with a complex
      karyotype showing both t(1;19) and t(14;18). Two reports of this phenomenon have
      been published previously and molecular analysis, where performed, showed the E2A
      gene was not rearranged, suggesting the t(1;19) was a molecular variant of the
      established translocation. In contrast, molecular analysis of our case
      demonstrated expression of the E2A/PBX1 fusion transcript typically associated
      with t(1;19) in pre-B ALL but showed it to be present at an extremely low level,
      despite the abnormal karyotype being found in the majority of metaphase cells.
      Analysis of bcl-2 expression showed a significant up-regulation. A down
      regulation of the E2A/PBX1 hybrid gene as a consequence of the enhanced
      expression of bcl-2 may be a possible mechanism for this finding.

PMID- 8757524
TI  - Multiplex PCR for rapid detection of T-cell receptor-gamma chain gene
      rearrangements in patients with lymphoproliferative diseases.
AB  - We describe a multiplex polymerase chain reaction (PCR) method suitable for the
      detection of all T-cell receptor (TCR) gamma-chain gene rearrangements in
      patients with lymphoproliferative diseases. 40 patients with various
      lymphoproliferative disorders and 40 healthy individuals were tested. Clonal TCR
      gamma rearrangements were identified in all patients with malignant disorders,
      and in one of 10 cases with established reactive lymphocytosis but not in normal
      controls. In all individuals testing positive, the patient's specific V and J
      segment involved in the rearrangement could be determined by simply splitting the
      multiplex primer mix. Our data show that the multiplex PCR technique enables
      rapid, simple and sensitive screening for clonal TCR gamma chain gene
      rearrangements.

PMID- 8757525
TI  - A randomized study comparing the effect of GM-CSF and G-CSF on immune
      reconstitution after autologous bone marrow transplantation.
AB  - Haemopoietic growth factors (HGFs) have been shown to accelerate recovery from
      severe neutropenia after autologous bone marrow transplantation (ABMT) but their
      effect on immune reconstitution is not well defined. The present study compares,
      through randomized trial, the in vivo effect of GM-CSF and G-CSF administration
      on the immune recovery of patients who underwent ABMT. For that purpose, we have
      sequentially analysed 14 different T, B and NK lymphoid cell subsets using
      appropriate dual staining during the first year following transplant (days +6,
      +17, +31, +66, +90, +120, +180, +360). 24 patients with lymphoproliferative
      disorders (20 lymphomas and four multiple myelomas) and who had undergone ABMT
      were included in the study. The median age was 43 years (range 22-62 years). All
      lymphoma patients were homogenously conditioned with BEAM. Our results show that
      both GM-CSF and G-CSF aid T-cell (CD3+/alpha beta) recovery though their
      contribution varies depending on the T-cell subset analysed. G-CSF contributed to
      a significantly faster recovery of CD8+ cells (P = 0.03). The CD8+ cell
      regeneration was produced mainly by activated cells (CD38+/HLA-DR+) which lacked
      the CD11b antigen. In contrast, GM-CSF favoured the regeneration of CD4+ cells
      (through both the CD45RO+ and CD45RA+ subset), leading to a higher CD4+:CD8+
      ratio (P = 0.007). No statistically significant differences were detected in the
      three groups of patients as regards both the recovery of NK cells and NK
      activity. Furthermore, the use of HGF did not seem to exert a significant
      influence on the recovery of B lymphocytes. This recovery was based on the CD5+
      subpopulation that showed a rapid rise after the first month. We suggest that G
      CSF and GM-CSF not only influence myeloid recovery, but also regeneration of the
      immune system after ABMT.

PMID- 8757526
TI  - Collection and transplantation of peripheral blood progenitor cells mobilized by
      G-CSF alone in children with malignancies.
AB  - Results of collection and transplantation of peripheral blood progenitor cells
      (PBPC) mobilized by G-CSF in 31 children with different malignancies were
      analysed. A total of 43 aphereses were performed, following administration of
      granulocyte colony-stimulating factor (G-CSF), using a continuous flow blood cell
      separator (Cobe Spectra) through a central venous catheter. For patients weighing
      <or= 25 kg the extracorporeal line was primed with red blood cells. The mean
      blood flow rate was 33.2 ml/min (range 12-56 ml/min). The mean number of
      mononuclear cells (MNC), granulocyte-macrophage colony-forming units (CFU-GM) and
      CD34+ cells collected were 7.22 x 10(8)/kg body weight (b.w.), 15.9 x 10(4)/kg
      and 5.44 x 10(6)/kg respectively. The morbidity related to PBPC collection was
      low and the mean apheresis time was 302.7 min (range 115-492). The volume of
      processed blood for apheresis (per kilogram body weight) ranged from 117 to 539.6
      (mean 309.13 ml/kg). 20 patients required only one apheresis to collect the
      minimum requirement of 5 - 7 x 10(8)/kg of MNC. All patients subsequently
      underwent autografting with PBPC after myeloablative therapy. Days to achieve an
      absolute count of neutrophils (ANC) > 0.5 x 10(9)/l and a platelet count of 20 x
      10(9)/l without platelet support were 9.5 and 18, respectively. The number of
      CD34+ cells infused correlated highly with engraftment kinetics. The extra
      medullary toxicity was low and manageable.

PMID- 8757527
TI  - Transient neutropenia in normal donors after G-CSF mobilization and stem cell
      apheresis.
AB  - Thirteen normal adult donors underwent daily leukapheresis for peripheral blood
      progenitor cell collection for allografting beginning on day 4 or 5 of G-CSF
      mobilization (12 micrograms/kg/d). They had complete blood counts performed 7-10
      d after the completion of the procedure. A reduction in the total leucocyte count
      below baseline levels, accounted for by a decrease in the absolute neutrophil
      (ANC) and lymphocyte counts, was noted. Neutropenia (ANC < 1.5 x 10(9)/l)
      occurred in two (15%) of the donors. The lowest ANC observed was 0.6 x 10(9)/l.
      The neutropenia was asymptomatic and resolved on follow-up evaluation.

PMID- 8757528
TI  - Investigation of chronic hepatitis C infection in individuals with haemophilia:
      assessment of invasive and non-invasive methods.
AB  - Hepatitis C virus (HCV) infection is the major cause of chronic liver disease in
      individuals with haemophilia. A wide spectrum of disease severity is found in
      this group, ranging from mild hepatitis to cirrhosis. We have studied a cohort of
      87 anti-HCV positive haemophiliacs who have been infected with HCV for 10-25
      years and assessed the relative value of invasive and non-invasive methods of
      evaluating liver disease. The severity of liver disease was assessed using
      ultrasound scan (n = 77), upper GI endoscopy (n = 50), laparoscopic liver
      inspection (n = 33) and liver biopsy (n = 22). Invasive investigations were
      performed without any significant bleeding complications. Evidence of severe
      liver disease was found in approximately 25% of patients. There was agreement
      between the severity of liver histology and the information derived from the
      laparoscopic liver inspection, endoscopy and ultrasound in 86%. Co-infection with
      HIV was significantly associated with more severe liver disease (P = 0.006). This
      study provides further evidence that liver disease is emerging as a major
      complication in haemophiliacs and severe liver disease is more common in those co
      infected with HIV. We have shown the potential value of laparoscopic liver
      inspection, in combination with endoscopy and ultrasound, in staging the extent
      of liver disease, and suggest that most patients may be managed without resorting
      to liver biopsy.

PMID- 8757529
TI  - Coexistence of familial antiphospholipid syndrome and factor V Leiden: impact on
      thrombotic diathesis.
AB  - Two young siblings who presented with an unusual recurrent severe thromboembolic
      phenomenon were found to have familial anti-phospholipid syndrome and were
      heterozygous for the factor V R506Q mutation. The coexistence of hereditary and
      acquired APC-resistance may explain the severity of thromboembolism.

PMID- 8757530
TI  - Clinical usefulness of desmopressin for prevention of surgical bleeding in
      patients with symptomatic heterozygous factor XI deficiency.
AB  - Heterozygous factor XI (FXI) deficiency is sometimes associated with a
      significant bleeding tendency. Fresh frozen plasma of FXI concentrates are the
      mainstay of treatment in patients with a clear bleeding history, especially prior
      to surgery. However, these treatments are not completely free of risk.
      Furthermore, thrombosis has been reported in patients with FXI deficiency infused
      with FXI concentrate. No data are available on the possible efficacy of
      desmopressin in these patients. Two patients with a clear bleeding history
      associated with FXI deficiency and no additional haemostatic defects agreed to be
      treated with desmopressin before carpal tunnel surgery and dental extraction. The
      reduced basal FXI activity and antigen levels slightly increased after infusion,
      reaching borderline values. No bleeding was observed after surgical procedures.
      Desmopressin treatment seems a reasonable and useful choice in symptomatic,
      heterozygous FXI-deficient patients, thus reducing the cost of treatment, the
      risk of transmission of blood-borne viruses, and of thrombosis.

PMID- 8757531
TI  - Cyclic change of cytokines in a patient with cyclic thrombocytopenia.
AB  - The serial change of various cytokines in the serum from a patient with cyclic
      thrombocytopenia is described. Interleukin 7, stem cell factor, and transforming
      growth factor beta 1 synchronized with the platelet count, and there was a
      significant positive correlation between the three cytokines and the platelet
      count. Levels of macrophage colony-stimulating factor, thrombopoietin, platelet
      associated IgG and erythropoietin changed reciprocally with the platelet count,
      and there was a significant negative correlation between the platelet count and
      these cytokines except erythropoietin. No cyclic change was observed in IL-3, IL
      6, IL-11, granulocyte-macrophage colony-stimulating factor, or leukaemia
      inhibitory factor. These observations suggest that this disease involves two
      cyclic changes: megakaryocytopoiesis and platelet destruction, in both of which
      the cytokines play an important role.

PMID- 8757532
TI  - Antigen topography is critical for interaction of IgG2 anti-red-cell antibodies
      with Fc gamma receptors.
AB  - IgG antibodies to the Rh D polypeptide on red cells are normally IgG1 or IgG3,
      whereas antibodies produced in response to carbohydrate antigens such as the A
      and B blood groups are predominantly IgG2. The consequences of this isotype
      restriction for the immune destruction of red cells were investigated. Human IgG2
      anti-D and IgG2 anti-A were isolated by affinity purification from an unusual
      anti-D serum (DEL) and anti-A sera, respectively. These antibodies were compared
      with IgG1 and IgG3 monoclonal anti-D in in vitro functional assays of the
      interaction between IgG-coated red cells (EA-IgG) and cells bearing IgG Fc
      receptors (Fc gamma R). Dimeric IgG2 anti-D bound efficiently to cell lines
      transfected with Fc gamma RIIa-H131, an allotypic form of Fc gamma RIIa which
      readily interacts with IgG2, IgG1 and IgG3. Unexpectedly, however, -D- phenotype
      red cells coated with IgG2 anti-D did not form rosettes with these cells, whereas
      EA-IgG2 anti-A and EA-IgG1 and EA-IgG3 anti-D effectively formed rosettes with
      these transfectants at the same sensitization level (100,000 molecules IgG/red
      cell). In antibody-dependent cell-mediated cytotoxicity (ADCC) assays, lysis of
      EA-IgG2 anti-A was mediated via Fc gamma RIIa, whereas lysis of EA-IgG1 and EA
      IgG3 anti-D was mediated via Fc gamma RI or Fc gamma RIII; EA-IgG2 anti-D was
      inactive in all functional assays. These experiments suggest that both IgG
      subclass and antigen structure affect functional IgG-Fc gamma R interactions. The
      topography of the Rh D antigen, an integral membrane protein, ensures that anti-D
      is bound near the lipid bilayer surrounded by the glycocalyx. This may sterically
      hinder access of Fc gamma RIIa-H131 to the Fc gamma R recognition site on the
      relatively inflexible IgG2 anti-D, but not to that of IgG1 or IgG3 anti-D. In
      contrast, IgG2 bound to the A antigen on glycoproteins is not so constrained. The
      topography of the D and A antigens may thus determine whether functional
      interactions of red-cell-bound IgG2 anti-D and IgG2 anti-A with cells bearing Fc
      gamma receptors can occur.

PMID- 8757533
TI  - Evaluation of a new, integral, whole blood filter (RS2000) system for prestorage
      leucodepletion of SAG-M red cells.
AB  - Residual donor leucocytes are responsible for many adverse transfusion reactions.
      Prestorage leucodepletion may ameliorate these effects and enhance product
      quality. We studied a bottom and top (BAT) system incorporating an integral
      filter for whole blood leucodepletion. Our evaluation assessed leucodepletion
      efficiency as well as in vitro SAG-M red cell quality and storage
      characteristics. Sixty-six units of blood were collected; test units into the
      Optipac-pLuS system and controls into the standard triple pack configuration.
      Test units were held for 4-6 h at room temperature (rt) or 12-18 h at 4 degrees
      C. The mean leucocyte counts for the SAG-M red cells in the quality and storage
      trial were 0.6 x 10(6) (rt hold), 0.05 x 10(6) (4 degrees C hold) and 2500 x
      10(6) (controls). We observed no significant differences between the groups for
      Na+, ATP, 2,3-DPG, glucose, lactate and pH during the 49 d storage. The control
      group, however, showed a greater increase in haemolysis and K+ with time.
      Autologous in vivo 24 h red cell recovery, after 42 d storage, was > 75%.
      Adjustment of processing parameters in subsequent studies gave leucodepleted SAG
      M red cells with minimal cell loss (9.19%) plus acceptable haemoglobin content
      (46-76 g/U) and haematocrit (54-62%). This system achieved > 3.5 log
      leucodepletion with all but one unit containing < 1 x 10(6) leucocytes. The
      product quality is good and the system suitable for routine use in blood centres.

PMID- 8757534
TI  - A novel mutation in the ferrochelatase gene associated with erythropoietic
      protoporphyria.
AB  - Erythropoietic protoporphyria (EPP) is a hereditary disorder caused by mutations
      of the ferrochelatase gene. We investigated a Japanese patient with a dominant
      form of erythropoietic protoporphyria for a ferrochelatase mutation. Sequence
      analysis of the proband's ferrochelatase cDNA revealed a T to C point mutation at
      nucleotide 557. This mutation resulted in the replacement of Ile by Thr at amino
      acid position 186, a novel mutation in erythropoietic protoporphyria. An increase
      in ferrochelatase activity was not observed in the crude extract of E. coli over
      expressing the mutant protein compared with the control, whereas a marked
      increase in activity was observed in that over-expressing the wild type.
      Prediction of the secondary structure of ferrochelatase suggested that the Ile186
      ->Thr mutation changed the original beta-sheet structure to an alpha helix in the
      region including amino acid residue of mutation. We conclude that, in the
      patient, the Ile186-->Thr mutation had abolished enzyme activity, possibly by
      disrupting the secondary structure, thereby causing erythropoietic
      protoporphyria.

PMID- 8757535
TI  - Phenotype, genotype and clonality of Reed-Sternberg cells in nodular sclerosis
      Hodgkin's disease: results of a single-cell study.
AB  - The genotype and clonality of Reed-Sternberg (RS) cells in Hodgkin's disease (HD)
      has remained a controversial issue, largely due to the scarcity of RS cells in
      tissues and the limitations of the techniques used to resolve this issue.
      Southern hybridization and polymerase chain reaction (PCR) assays using DNA
      extracted from tissues can only document clonal gene rearrangements, but do not
      indicate which cellular population is responsible for such rearrangements. To
      overcome the limitations of these previous techniques for studying the genotype
      and clonality of RS cells, we analysed single RS cells with a single-cell PCR
      assay to detect immunoglobulin heavy chain gene (IgH) rearrangements and X
      chromosome inactivation. Six cases of nodular sclerosis (NS) HD were studied. The
      RS cells displayed a B-cell phenotype in three cases and a null-cell phenotype in
      the other three cases. IgH rearrangements were detected in the RS cells of the
      three cases with a B-cell phenotype, but not in the other cases. In these three
      cases the IgH rearrangements in the RS cells were polyclonal, although a
      subpopulation of clonal RS cells was documented in one case. The finding that the
      RS cells with IgH rearrangements were not monoclonal was supported in one case by
      studying the pattern of X-chromosome inactivation in single RS cells by a single
      cell human androgen receptor gene (HUMARA) PCR assay. Our results indicate that
      NSHD begins as a polyclonal process in which a clonal RS cell population may
      arise; and that the RS cells in a subset of NSHD show evidence of B-lineage
      differentiation.

PMID- 8757536
TI  - The bone marrow aspirate of healthy subjects.
AB  - Bone marrow aspirates were obtained from the right or left posterior superior
      iliac spine of 50 healthy volunteers, 30 men and 20 women. Reference ranges were
      derived for each cell type and for the myeloid:erythroid  (M:E) ratio. The M:E
      ratio and the percentage of neutrophils were significantly higher in the women
      and the erythroid component significantly lower. All 28 evaluable men and 11/17
      evaluable women had storage iron present in more than trace amounts. The
      percentage of erythroblasts with detectable iron granules varied very widely,
      from 3% to 69% in those with more than a trace of storage iron. Minor
      dyserythropoietic features were present in a high percentage of subjects and
      19/50 subjects had one or two dysplastic megakaryocytes. Granulocytic dysplasia
      was not detected.

PMID- 8757537
TI  - Aprotinin employment in patients with acute leukaemia to prevent haemorrhage
      during pulmonary aspergillosis.

PMID- 8757538
TI  - IL-10 serum levels in B-cell chronic lymphocytic leukaemia.

PMID- 8757540
TI  - [Between pure and applied science: dilemmas in the evaluation of scientific
      research].

PMID- 8757539
TI  - [Opinion about the special issue, "Ten years of AIDS in Mexico"].

PMID- 8757541
TI  - [Urban-rural variations in medical care of children with diarrhea in Mexico].
AB  - OBJECTIVE: To study the urban and rural variations of medical care for acute
      diarrhea among children under five years old. MATERIAL AND METHODS: Data from the
      1993 Effective Household Treatment National Survey were analyzed. A number of 338
      children from urban areas and 300 from rural areas were included in the study.
      Variables included were: household treatment, health-seeking behavior, mothers'
      previous training to manage acute diarrhea, use of oral rehydration salts (ORS)
      and availability of and access to health care. RESULTS: Oral rehydration therapy
      (ORT) as part of the household treatment and feeding the regular diet were more
      frequently found in rural areas. Less than 50% of children received medical care
      in both settings. In urban areas most children were cared for by private
      physicians. About 30% of children needed medical care but they were not taken to
      medical facilities. Physicians in rural areas prescribed ORS more frequently,
      while those from urban areas prescribed medication and restrictive diets in a
      greater proportion. Physicians working in public facilities prescribed ORT in
      greater proportions than private ones. Mothers from rural areas had received more
      training to manage diarrhea but they had restricted access to medical care in
      comparison to mothers from urban areas. CONCLUSIONS: It is necessary to improve
      health care education of urban populations, to increase access and coverage of
      health services in rural areas and to strength activities to improve the quality
      of medical care provided by private physicians and by those working in urban
      areas.

PMID- 8757542
TI  - [Educational intervention for preventing dehydration in diarrheal diseases in
      Tlapacoyan, Mexico].
AB  - OBJECTIVES: To deliver an educational intervention to teach mothers self-care
      measures to manage children's diarrhea and dehydration. MATERIAL AND METHODS: A
      controlled community trial intervention was designed (with control group)
      consisting of 180 mothers of children aged under five. The study was conducted in
      the city of Tlapacoyan, Veracruz, Mexico. Differences were measured for 17 main
      concepts and compared between the experimental group and the control group.
      Comparisons before and after the intervention were controlled for mother's age,
      education and previous training. RESULTS: All 17 concepts showed per cent changes
      that ranged between 30% and 100% for the intervention group, and between 13% to
      41% for the control group. Chi square values were used to test statistical
      significance, to ensure that differences were due to the intervention and not to
      chance. CONCLUSIONS: A multichannel educational intervention is a culturally
      sensitive intervention that shows better results than a face-to-face
      intervention. It should be used for those groups that are at high risk of death
      due to dehydration associated to diarrhea, even when oral rehydration salts are
      available.

PMID- 8757543
TI  - [Overweight in 12-49 year-old women and children under 5 years of age in Mexico].
AB  - OBJECTIVE: To estimate the association between some sociodemographic
      characteristics and the risk of obesity among 12-49 year-old women and children
      aged under five. MATERIAL AND METHODS: We analyzed data from Mexico's 1988
      National Nutrition Survey, including information on 15 811 women of child-bearing
      age and 6 987 children aged under five years. We estimated the obesity prevalence
      rate ratios and confidence intervals for all the variables of interest. RESULTS:
      Preschool children living in the north and central regions of Mexico presented
      higher obesity prevalence rates than those living in the southeast (PR = 1.90,
      95% CI 1.41-2.59 and PR = 1.91, 95% CI 1.41-2.59, respectively). The risk of
      obesity was positively associated to the educational level of the head of the
      household. The prevalence of obesity was greater among child-bearing age women
      living in the northern region of Mexico and in Mexico City (PR = 1.21, 95% CI
      1.10-1.34 and PR = 1.16, 95% CI 1.05-1.28). The prevalence of obesity was also
      positively associated with the number of live births and negatively associated
      with the woman's educational level. CONCLUSIONS: It is necessary to implement
      obesity prevention programs among high risk groups.

PMID- 8757544
TI  - [Risk factors for asthenopia among computer terminal operators].
AB  - OBJECTIVE: To study the incidence of asthenopia among computer terminal operators
      as compared to unexposed administrative workers and to identify the risk factors
      associated with this condition. MATERIAL AND METHODS: A sample of 35 computer
      terminal operators and 70 unexposed administrative workers from eight computing
      centers at an educational institution were included in the study. The risk
      factors studied were: lighting, contrast, type of lighting, screen type,
      electrostatic field, eye to monitor distance, time and number of hours worked,
      age, use of corrective lenses, seniority and overtime. Asthenopia was clinically
      identified as the presence of at least one sign and symptom present in a given
      workday. RESULTS: Asthenopia was found in 68.5% of the exposed group and in 47.7%
      of the unexposed group (p < 0.05). Among the risk factors studied, working for
      more than four hours at the video display terminal was shown to have a
      significant association with asthenopia (p < 0.05). CONCLUSIONS: A recommendation
      is made to take breaks during the workday at computer terminals in order to avoid
      visual fatigue. Also, more extensive studies should be carried out in our
      population to establish safety criteria and to standardize work activities using
      computer terminals.

PMID- 8757545
TI  - [Epidemiology of suicide in Mexico, 1970-1984].
AB  - OBJECTIVE: This paper reports data of suicide as a cause of death in Mexico from
      1970 to 1994. MATERIAL AND METHODS: Death certificates and census data were used
      as the main sources for this study. RESULTS: In 1970 554 suicide deaths were
      reported for both genders. In 1994 there were 2 603 deaths. During this period
      the suicide death rate increased from 1.13 per 100 000 inhabitants to 2.89 per
      100 000 inhabitants, which represents an increase of 156% in 24 years.
      Nevertheless, a higher increase was seen among males; 169% for this period as
      compared to 98% among females. In 1970 the proportional suicide mortality rate
      was 0.11% of total deaths; in 1994, an increase to 0.62% was observed. During the
      study period, the highest increase in the suicide rate was seen in the older
      groups (65 years and over). Nevertheless, an increase was also seen among the
      younger population (those aged under 19 years). In 1994, the last year of the
      series, the highest rates were found among males, especially among those aged 65
      and over. Differences were found also in the suicide rates among the states of
      the Mexican Republic. In 1994 the State of Tlaxcala and the State of Mexico
      reported the lowest rates. The highest rates were found in Tabasco and Campeche.
      Thus, the highest suicide rates were seen in the southeast and the lowest rates
      in the central part of the country. CONCLUSIONS: Suicide is a growing problem in
      Mexico, mainly occurring among male older adults. Nevertheless, growing rates
      among young adults call for suicide prevention and care programs.

PMID- 8757546
TI  - [Simplified CD4+ T-lymphocyte count in patients with HIV/AIDS in Mexico].
AB  - OBJECTIVE: To study the correlation between ALC and CD4 cell counts and to find
      alternative ways of counting CD4+ T-lymphocytes. MATERIAL AND METHODS: The double
      positivity for CD3/CD4 antibodies was measured in 175 consecutive HIV-positive
      patients using flow cytometry; in these cases a difference was made between
      counting cells that were positive for both antibodies vs those that were positive
      only to CD4. ALC and CD4 counts were also compared among 500 subjects infected
      with HIV, using linear regression analysis and comparing the number of dissimilar
      cases for counts below 200 cells/microliters and ALC counts lower than 1 500 and
      2000 cells/microliters. RESULTS: In the 175 cases measured by the CD3/CD4
      antibody combination the mean percent was 13.8% and for total CD4 cells 14.2% (p
      = NS); the mean difference was 0.4% and the median 0.2%. For the 500 patients the
      mean ALC was 1 700 cells/microliters and the mean CD4 count was 219
      cells/microliters; the correlation coefficient was 0.59. CONCLUSIONS: These data
      suggest a poor correlation of ALC and CD4 cell counts, thus it is impossible to
      predict CD4 on the basis of ALC. This is the reason why it is necessary to
      measure CD4 cells separately. The difference between measuring double positive
      CD3/CD4 cells vs only CD4 positive cells was not significant. Our data suggest
      that the use of a single CD4 antibody may cut costs and still produce clinically
      useful information.

PMID- 8757547
TI  - [Incidence of common ophthalmological disorders in preschool children in Mexico
      City].
AB  - OBJECTIVE: To estimate the prevalence of undetected vision abnormalities among
      preschool children. These problems can lead to a variety of adverse consequences,
      the most serious being amblyopia, which becomes irreversible after the fifth year
      without treatment. In some other countries there are screening programs to
      identify visual abnormalities among four year old children. In our country there
      are no studies about the prevalence of this problem among preschool children.
      MATERIAL AND METHODS: A total of 39 preschool children were randomly selected
      from 93 kindergarten schools in a District of Mexico City. In total, 343 children
      were screened for ophthalmologic abnormalities by two pediatricians who were
      previously trained for this purpose. RESULTS: Fifty-seven (16.6%) children failed
      the visual acuity testing: four had strabismus, four cataract, and one glaucoma,
      and 48 refraction defects. Only 13 (3.8%) had been previously examined, ever.
      CONCLUSIONS: We consider that the prevalence found supports the recommendation to
      promote ophthalmologic examining as part of the routinary child care practice and
      to perform preventive preschool screening.

PMID- 8757548
TI  - [Education and women's health: reflections from a gender perspective].
AB  - Using a gender perspective, this paper presents a critical bibliographic review
      of several projects and experiences focused on education and women's health. It
      aims to analyze some assumptions related to women's health on which different
      works and practices are based and reproduced in society. Several examples are
      given which, by illustrating women's living conditions and their experiences,
      make it possible to visualize some links between women's oppressed conditions of
      living and their health conditions. This paper concludes by emphasizing the need
      to constantly analyze social reality from a critical viewpoint; this would enable
      us to question and reformulate the logic underlying social organizations and
      health care, which emphasizes the women's maternal role and overlooks their
      health and well-being as a whole.

PMID- 8757549
TI  - Supply and demand.

PMID- 8757550
TI  - Can we change the system?

PMID- 8757551
TI  - Dementia: the role of potentially treatable psychiatric etiologies.

PMID- 8757552
TI  - Lymphangiomatous cyst of the adrenal gland: an unusual cause of flank pain.
AB  - Cysts of the adrenal gland are rarely encountered in clinical practice.
      Presenting signs and symptoms are variable. We present a case of an active 46
      year old white female with six months history of left flank pain who was found to
      have a large lymphangiomatous cyst of the left adrenal gland. Curative resection
      of the cyst and left adrenalectomy were performed with preservation of the left
      kidney. We include a review of the literature.

PMID- 8757553
TI  - Diagnosis of vasa previa with ultrasound and color flow Doppler: a case report.
AB  - Ultrasound and Doppler imaging have proven to be valuable antepartum diagnostic
      tools for the early recognition of vasa previa. Recent reports have demonstrated
      that successful detection and timely management can subsequently reduce the risk
      of a life-threatening fetal hemorrhage. We present the fourth reported case of
      vasa previa detected antenatally by ultrasound. While conscientious attention to
      the risk factors and a high index of clinical suspicion remain important
      considerations, we believe that ultrasound and color Doppler flow analysis
      represent a highly sensitive diagnostic tool for those patients at risk. In the
      past, antenatal diagnosis has relied on insensitive and inconclusive means, often
      only after signs of fetal compromise have become apparent. Sonography has been
      demonstrated to offer reduced fetal mortality and therefore must be considered
      the new standard of care for management of suspected vasa previa.

PMID- 8757554
TI  - Multiple endocrine neoplasia syndrome type 1 presenting with hip fracture: a case
      report.

PMID- 8757555
TI  - Chromosome 22q11 monosomy and the genetic basis of congenital heart disease.

PMID- 8757556
TI  - Photographic analysis: a quantitative approach to the evaluation of
      dysmorphology.

PMID- 8757557
TI  - Rational approach to pharmacologic reduction of cholesterol levels in children.

PMID- 8757558
TI  - Recent advances in the genetics of primary immunodeficiency syndromes.

PMID- 8757559
TI  - Importance of microdeletions of chromosomal region 22q11 as a cause of selected
      malformations of the ventricular outflow tracts and aortic arch: a three-year
      prospective study.
AB  - OBJECTIVES: To assess the incidence of microdeletions of chromosomal region 22q11
      in a population of infants coming to a regional pediatric cardiac center with
      selected abnormalities of the ventricular outflow tracts and aortic arch and,
      further, to provide phenotypic/genetic correlations to determine whether patients
      with 22q11 deletions can be clinically recognized in infancy. BACKGROUND:
      DiGeorge syndrome and velocardiofacial syndrome are frequently associated with
      malformations of the ventricular outflow tracts and aortic arch. Both are usually
      caused by microdeletions of chromosomal region 22q11. The overall importance of
      such deletions as a cause of these cardiac malformations remains to be
      established. STUDY DESIGN: All infants with the candidate cardiac phenotypes
      during a 34-month period were studied. Dysmorphic features, type of cardiac
      defect, serum calcium concentration, and thymic status were recorded. Cytogenetic
      studies, including high-resolution karyotyping and fluorescence in situ
      hybridization using cosmids (cEO or cH748) from the DiGeorge critical region,
      were performed after clinical assessment. RESULTS: Fifty infants (including 36
      with tetralogy of Fallot with or without pulmonary atresia) were seen during the
      study period. Twenty-six infants (52%) were dysmorphic, including 19 who were
      considered to have a phenotypic appearance consistent with 22q11 deletion.
      Genetic analysis confirmed hemizygosity for 22q11 in 8 of these 19 cases. Results
      of fluorescence in situ hybridization studies were normal in 22 infants without
      dysmorphic features and in 5 infants with dysmorphic features not suggestive of a
      22q11 deletion. CONCLUSIONS: Microdeletions of chromosomal region 22q11 are an
      important cause of selected malformations of the ventricular outflow tracts and
      aortic arch and account for about 15% to 20% of cases. These deletions may be
      clinically recognized in early infancy and can be rapidly confirmed by
      fluorescence in situ hybridization.

PMID- 8757560
TI  - A case definition and photographic screening tool for the facial phenotype of
      fetal alcohol syndrome.
AB  - OBJECTIVES: The purpose of this study was to demonstrate that a quantitative,
      multivariate case definition of the fetal alcohol syndrome (FAS) facial phenotype
      could be derived from photographs of individuals with FAS and to demonstrate how
      this case definition and photographic approach could be used to develop
      efficient, accurate, and precise screening tools, diagnostic aids, and possibly
      surveillance tools. STUDY DESIGN: Frontal facial photographs of 42 subjects (from
      birth to 27 years of age) with FAS were matched to 84 subjects without FAS. The
      study population was randomly divided in half. Group 1 was used to identify the
      facial features that best differentiated individuals with and without FAS. Group
      2 was used for cross validation. RESULTS: In group 1, stepwise discriminant
      analysis identified three facial features (reduced palpebral fissure length/inner
      canthal distance ratio, smooth philtrum, and thin upper lip) as the cluster of
      features that differentiated individuals with and without FAS in groups 1 and 2
      with 100% accuracy. Sensitivity and specificity were unaffected by race, gender,
      and age. CONCLUSIONS: The phenotypic case definition derived from photographs
      accurately distinguished between individuals with and without FAS, demonstrating
      the potential of this approach for developing screening, diagnostic, and
      surveillance tools. Further evaluation of the validity and generalizability of
      this method will be needed.

PMID- 8757561
TI  - Efficacy and safety of cholestyramine therapy in peripubertal and prepubertal
      children with familial hypercholesterolemia.
AB  - OBJECTIVE: To determine the efficacy and safety of cholestyramine therapy in
      young children with familial hypercholesterolemia. SUBJECTS: Boys aged 6 to 11
      years (n = 57) and girls aged 6 to 10 years (n = 39) with familial
      hypercholesterolemia. DESIGN: After 1 year of a low-fat, low-cholesterol diet,
      children with low-density lipoprotein (LDL) cholesterol levels > or = 4.9 mmol/L
      (190 mg/di) or < or = 4.1 mmol/L (160 mg/dl) in the presence of familial
      premature cardiovascular disease were randomly assigned to a double-blind
      comparison of 8 gm cholestyramine (n = 36) and placebo (n = 36) for 1 year.
      OUTCOME MEASURES: The primary efficacy and safety outcomes were serum LDL
      cholesterol levels and height velocity, respectively. Secondary safety outcomes
      were erythrocyte folate, total plasma homocysteine, serum fat-soluble vitamins,
      and side effects. RESULTS: Twenty-two subjects in the cholestyramine group and 26
      in the placebo group completed the 1-year study. Most withdrawals from the study
      were related to unpalatability of the study drug or placebo. The LDL cholesterol
      levels changed by -16.9% (95% confidence interval, -10.8% to -22.9%) in the
      cholestyramine group compared with 1.4% (95% confidence interval, -4.4% to 7.2%)
      in the placebo group. Mean height velocity standard deviation scores during 1
      year for the children in the cholestyramine and the placebo groups who had not
      started puberty were 0.24 +/- 1.14 and 0.11 +/- 0.68, respectively (not
      significant). In the cholestyramine group, mean levels of 25-hydroxyvitamin D
      decreased. One girl had low folate and elevated homocysteine levels, and there
      was one case of intestinal obstruction caused by adhesions. CONCLUSIONS:
      Significant reductions in LDL cholesterol are achievable during treatment with
      cholestyramine in about half of eligible children. Growth is not adversely
      affected. Folate deficiency may occur, even with a low dose of cholestyramine,
      and vitamin D supplements should be considered. Caution should possibly be
      exercised in starting cholestyramine therapy within 3 months of abdominal surgery
      in children.

PMID- 8757562
TI  - Wiskott-Aldrich syndrome in a family with Fanconi anemia.
AB  - Thrombocytopenia may be the presenting finding for both Wiskott-Aldrich syndrome
      and Fanconi anemia. We examined a sibship of four boys who had features of both
      of these hematologic disorders. Peripheral blood lymphocytes from three of the
      boys demonstrated DNA instability when cultured with diepoxybutane, confirming
      the diagnosis of Fanconi anemia in these patients. However, results of linkage
      analysis and X chromosome inactivation studies were consistent with the diagnosis
      of Wiskott-Aldrich syndrome in two of the boys, including one of the boys with
      Fanconi anemia. These findings could be attributed to the occurrence of two rare
      genetic disorders in a single family or to an unusual variant of Fanconi anemia.
      The recent identification of the Wiskott-Aldrich gene permitted us to address
      this question directly. Epstein-Barr virus-transformed cell lines from the two
      boys thought to have Wiskott-Aldrich syndrome on the basis of linkage analysis
      failed to express transcripts for the Wiskott-Aldrich gene. Genomic DNA from
      these two patients demonstrated a G insertion in the tenth exon of the Wiskott
      Aldrich gene, resulting in a frameshift and a premature stop codon. Surprisingly,
      the patient with Fanconi anemia and a null mutation in the Wiskott-Aldrich gene
      had typical Fanconi anemia but mild Wiskott-Aldrich syndrome.

PMID- 8757563
TI  - Isolated X-linked thrombocytopenia in two unrelated families is associated with
      point mutations in the Wiskott-Aldrich syndrome protein gene.
AB  - The Wiskott-Aldrich syndrome (WAS) is characterized by defective platelet and
      lymphocyte function associated with eczema and increased susceptibility to
      malignancies. It is caused by mutations of the WAS protein-encoding gene (WASP).
      X-lined thrombocytopenia, defined by low platelet counts and volume, may be an
      allelic variant of WAS. In patients with XLT from two unrelated families, WASP
      gene defects were identified by single-strand conformational polymorphism and by
      sequencing. Point mutations in exon 2 of the WASP gene were found in the patients
      from both families in which XLT segregated. Several obligate heterozygote female
      members of these families display a random pattern of X inactivation in their
      peripheral blood leukocytes. This study shows that XLT may be caused by mutations
      of the WASP, thus representing an allelic variant of WAS.

PMID- 8757564
TI  - Late-onset sepsis in very low birth weight neonates: a report from the National
      Institute of Child Health and Human Development Neonatal Research Network.
AB  - OBJECTIVE: Late-onset sepsis (occurring after 3 days of age) is an important
      problem in very low birth weight (VLBW) infants. To determine the current
      incidence of late-onset sepsis, risk factors for disease, and the impact of late
      onset sepsis on subsequent hospital course, we evaluated a cohort of 7861 VLBW
      (401 to 1500 gm) neonates admitted to the 12 National Institute of Child Health
      and Human Development (NICHD) Neonatal Research Network centers during a 32-month
      period (1991 to 1993). METHODS: The NICHD Neonatal Research Network maintains a
      prospectively collected registry of all VLBW neonates cared for at participating
      centers. Data from this registry were analyzed retrospectively. RESULTS: Of 6911
      infants who survived beyond 3 days, 1696 (25%) had one or more episodes of blood
      culture-proven sepsis. The vast majority of infection (73%) were caused by gram
      positive organisms, with coagulase-negative staphylococci accounting for 55% of
      all infections. Rate of infection was inversely related to birth weight and
      gestational age. Complications of prematurity associated with an increased rate
      of infection included intubation, respiratory distress syndrome, prolonged
      ventilation, bronchopulmonary dysplasia, patent ductus arteriosus, severe
      intraventricular hemorrhage, and necrotizing enterocolitis. Among infants with
      bronchopulmonary dysplasia, those with late-onset sepsis had a significantly
      longer duration of mechanical ventilation (45 vs 33 days; p <0.01). Late-onset
      sepsis prolonged hospital stay: the mean number of days in the hospital for VLBW
      neonates with and without late-onset sepsis was 86 and 61 days, respectively (p
      <0.001). Even after adjustment for other complications of prematurity, including
      intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary
      dysplasia, infants with late-onset sepsis had a significantly longer
      hospitalization (p <0.001). Moreover, neonates in whom late-onset sepsis
      developed were significantly more likely to die than those who were uninfected
      (17% vs 7%; p <0.000 1), especially if they were infected with gram-negative
      organisms (40%) or fungi (28%). Deaths attributed to infection increased with
      increasing chronologic age. Whereas only 4% of deaths in the first 3 days of life
      were attributed to infection, 45% of deaths after 2 weeks were related to
      infection. CONCLUSIONS: Late-onset sepsis is a frequent and important problem
      among VLBW preterm infants. Successful strategies to decrease late-onset sepsis
      should decrease VLBW mortality rates, shorten hospital stay, and reduce costs.

PMID- 8757565
TI  - Early-onset sepsis in very low birth weight neonates: a report from the National
      Institute of Child Health and Human Development Neonatal Research Network.
AB  - OBJECTIVE: Early-onset sepsis (occurring within 72 hours of birth) is included in
      the differential diagnosis of most very low birth weight (VLBW) neonates. To
      determine the current incidence of early-onset sepsis, risk factors for disease,
      and the impact of early-onset sepsis on subsequent hospital course, we studied a
      cohort of 7861 VLBW neonates (401 to 1500 gm) admitted to the 12 National
      Institute of Child Health and Human Development (NICHD) Neonatal Research Network
      centers during a 32-month period (1991-1993). METHODS: The NICHD Neonatal
      Research Network maintains a prospectively collected registry on all VLBW
      neonates born or cared for at participating centers. Data from this registry were
      analyzed retrospectively. RESULTS: Blood culture-proven early-onset sepsis was
      uncommon, occurring in only 1.9% of VLBW neonates. Group B streptococcus was the
      most frequent pathogen associated with early-onset sepsis (31%), followed by
      Escherichia coli (16%) and Haemophilus influenzae (12%). Decreasing gestational
      age was associated with increased rates of infection. Antibiotic therapy for
      suspected sepsis is frequently initiated at birth in VLBW neonates. Almost half
      of the infants in this cohort were considered to have clinical sepsis and
      continued to receive antibiotics for 5 or more days, despite a negative blood
      culture result in 98% of cases. These findings underscore the difficulty of
      ruling out sepsis in the symptomatic immature neonate and the special concern for
      culture-negative clinical sepsis in the face of maternal antibiotic use. Neonates
      with early-onset sepsis were significantly more likely to have subsequent
      comorbidities, including severe intraventricular hemorrhage, patent ductus
      arteriosus, and prolonged assisted ventilation. Although 26% of VLBW neonates
      with early-onset sepsis died, only 4% of the 950 deaths that occurred in the
      first 72 hours of life were attributed to infection. For those infants discharged
      alive, early-onset sepsis was associated with a significantly prolonged hospital
      stay (86 vs 69 days; p <0.02). CONCLUSIONS: Early-onset sepsis remains an
      important but uncommon problem among VLBW preterm infants. Improved diagnostic
      strategies are needed to enable the clinician to distinguish between the infected
      and the uninfected VLBW neonate with symptoms and to target continued antibiotic
      therapy to those who are truly infected.

PMID- 8757566
TI  - Clinical outcome of ulcerative colitis in children.
AB  - OBJECTIVES: To characterize the response to current medical therapies in children
      with ulcerative colitis, and to identify those factors that may predict the need
      for colectomy. DESIGN: Retrospective chart review at two large pediatric
      inflammatory bowel disease centers. RESULTS: We identified 171 subjects ranging
      in age from 1.5 to 17.7 years at diagnosis (mean 11.2 years). Mean follow-up was
      5.1 years. Of these subjects, 43% had mild disease at presentation and 57% had
      disease that was classified as moderate or severe. After treatment 90% of the
      former group and 81% of the latter group had resolution of symptoms by 6 months.
      During any subsequent yearly follow-up interval, approximately 55% of the entire
      study population was symptom free, 38% had chronic intermittent symptoms, and 7%
      had continuous symptoms. A significantly lower risk of colectomy was noted for
      those with initially mild disease compared with those with moderate/severe
      disease. At 1-year the risk of colectomy was 1% among those with mild disease
      versus 8% with moderate/severe disease; at 5 years, the risk of colectomy was 9%
      in the mild disease group versus 26% in the moderate/severe disease group (p
      <0.03). CONCLUSIONS: In the majority of pediatric subjects with ulcerative
      colitis remission is achieved in the first 6 months after therapy; thereafter
      disease is inactive in about 50% of patients during any given year of follow-up.
      Severity of disease at presentation is a significant risk factor for colectomy
      during the first 5 years of follow-up. Future management protocols with more
      aggressive initial therapy may be warranted in children with moderate/severe
      disease.

PMID- 8757567
TI  - Erythropoietin therapy in neonates at risk of having bronchopulmonary dysplasia
      and requiring multiple transfusions.
AB  - OBJECTIVES: To determine whether treatment with recombinant human erythropoietin
      (r-HuEPO) reduces transfusion requirements in premature neonates at risk of
      having bronchopulmonary dysplasia and requiring multiple transfusions. STUDY
      DESIGN: A double-blind, randomized, controlled trial. SUBJECTS: Fifty-five
      infants appropriate in weight for gestational age (less than 1250 gm birth
      weight) who, at 10 days of age, were predicted to have a greater than 75%
      probability of having bronchopulmonary dysplasia. This criterion had previously
      been shown to identify infants requiring multiple transfusions. Twenty-seven
      infants were randomly assigned to receive r-HuEPO therapy and 28 to a control
      group. r-HuEPO was administered in a dosage of 20 U/kg body weight,
      subcutaneously, three times a week for 6 weeks. Control infants received sham
      treatment. RESULTS: Infants treated with r-HuEPO required significantly fewer
      transfusions than control infants during their entire hospital stay (mean 3.48 +/
      1.58 vs 5.68 +/- 2.30; p = 0.0001) and had a higher mean reticulocyte count (p <
      or = 0.0005) and a higher mean hemoglobin concentration (p < or = 0.005) during
      the treatment period. At follow-up, 4 months after term, there were no
      significant differences between the groups in mean reticulocyte count (p = 0.86)
      or mean hemoglobin concentration (p = 0.56). However, two infants in each group
      had low serum ferritin values indicative of depleted iron stores. CONCLUSIONS:
      Treatment with r-HuEPO effectively stimulated erythropoiesis in premature infants
      at high risk of having bronchopulmonary dysplasia and requiring multiple
      transfusions; the result was a reduction in transfusion requirements. This
      treatment, together with other strategies to reduce the need for transfusions, is
      appropriate in this population. Unrelated to r-HuEPO treatment, these infants may
      be at risk of having iron deficiency later in infancy.

PMID- 8757568
TI  - Effect of recombinant human erythropoietin on insulin, amino acid, and lipid
      metabolism in uremia.
AB  - OBJECTIVE: To determine whether anemia is important in the pathogenesis of
      metabolic abnormalities in insulin, amino acid, and lipid metabolism in uremia.
      METHODS: Twelve adolescents (15 +/- 1 years of age) undergoing long-term dialysis
      were studied before and after correction of their anemia by human recombinant
      erythropoietin at a mean interval of 6 months. Six patients received
      hemodialysis, and six received continuous-cycling peritoneal dialysis. Insulin
      sensitivity was measured by the euglycemic clamp technique and insulin secretion
      by the hyperglycemic clamp technique in these patients. RESULTS: Hematocrit
      increased from 0.219 +/- 0.006 to 0.344 +/- 0.007 (p <0.01). Ferritin
      concentration did not change significantly (11,252 +/- 356 mg/dl to 785 +/- 226
      mg/dl). Serum iron concentration decreased from 134 +/- 13 mg/dl to 83 +/- 11
      mg/dl, and percentage saturation decreased from 56 +/- 4 to 41 +/- 5 (p <0.05 in
      both cases). There were no significant changes in weight, height, blood pressure,
      caloric intake, triceps skinfold thickness, or arm muscular area. There were also
      no significant changes in serum calcium, phosphate, bicarbonate, albumin,
      creatinine, or blood urea nitrogen concentration. Insulin sensitivity increased
      by 33% (p <0.01), but insulin secretion did not change significantly. Insulin
      sensitivity during the euglycemic clamp studies in patients before erythropoietin
      therapy was lower (145 +/- 10 mg/m2 per minute; p <0.01) than published normal
      values (201 +/- 12 mg/m2 per minute) and was normal after erythropoietin therapy
      (193 +/- 11 mg/m2 per minute). Insulin secretion was low in patients before
      erythropoietin therapy (44 +/- 8 microU/ml) compared with published normal values
      (68 +/- 6 microU/ml) and did not change after erythropoietin therapy (46 +/- 4
      microU/ml). Plasma concentrations of branched-chain amino acids and lipids in the
      patients were compared with values from eight healthy adolescents. Plasma
      concentrations of valine, leucine, and isoleucine were low before treatment and
      were normal after 6 months of erythropoietin therapy. Plasma concentrations of
      triglycerides, total cholesterol, and low-density lipoprotein cholesterol were
      all high before treatment and were normal after treatment of anemia. CONCLUSIONS:
      Treatment of anemia by erythropoietin reversed insulin resistance as well as
      amino acid and lipid abnormalities in adolescents undergoing dialysis.

PMID- 8757569
TI  - Elevated zinc protoporphyrin associated with thalassemia trait and hemoglobin E.
AB  - OBJECTIVE: Increased zinc protoporphyrin/heme (ZPP/H) ratio has been used in
      pediatrics to screen for iron deficiency and lead poisoning. This study was
      conducted to determine whether common hereditary hemoglobin disorders (alpha- and
      beta-thalassemia traits, hemoglobin E) found in U.S. minority groups are
      associated with an increase in the ZPP/H ratio in an iron-sufficient population.
      METHODS: The database was compiled from hemoglobinopathy screens performed
      between 1987 and 1993 at a regional referral laboratory in Washington State.
      ZPP/H ratio and hemoglobin type were obtained for 326 subjects between the ages
      of 15 and 49 years of age who were iron sufficient (serum ferritin levels > or =
      50 micrograms/L). RESULTS: The mean ZPP/H ratio was significantly higher (p <
      0.01) for subjects with beta-thalassemia trait (87 +/- 32 micromol/mol), (alpha
      thalassemia trait (73 +/- 37 micromol/mol), and hemoglobin E disorders (73 +/- 24
      micromol/mol) than for subjects with normal hemoglobin values (60 +/- 8
      micromol/mol). Fifty-one percent of subjects with beta-thalassemia trait, 22%
      with hemoglobin E, and 20% with alpha-thalassemia trait had elevated ZPP/H ratios
      (> 80 micromol/mol), compared with only 1.5% with normal hemoglobin values.
      CONCLUSIONS: The ZPP/H ratio is elevated in common hereditary hemoglobin
      disorders that mimic the microcytic anemia of iron deficiency, even in
      individuals without associated nutritional iron deficiency. For children who are
      treated for presumed iron deficiency, failure of the ZPP/H ratio to return to
      normal after adequate iron treatment, especially if microcytosis persists,
      indicates that a hereditary hemoglobin disorder may be present.

PMID- 8757570
TI  - Early detection of human immunodeficiency virus on dried blood spot specimens:
      sensitivity across serial specimens. Women and Infants Transmission Study Group.
AB  - OBJECTIVE: To evaluate the use of dried blood spot (DBS) specimens and the early
      diagnostic value of the polymerase chain reaction (PCR) for detection of the
      human immunodeficiency virus (HIV) in DBS specimens collected at predefined age
      intervals from a large cohort of U.S. infants at risk of congenital or perinatal
      HIV infection. DESIGN: We assayed available DBS specimens (n = 272) obtained
      during the first 4 months of life from 144 infants (41 infected, 103 uninfected)
      born to HIV-infected mothers enrolled in the Women and Infants Transmission
      Study. The DBS PCR results were compared with infant HIV infection status, PCR on
      liquid blood, and viral culture results. Analyses also included sensitivity and
      specificity of assay as related to the age of the infant when the specimen was
      obtained. RESULTS: The DBS specimen PCR results were concordant with results from
      liquid blood specimens and with results from viral culture. The DBS PCR was
      highly specific for all age groups. Sensitivity in detecting HIV infection status
      rapidly increased during the first month of life, from 19% (5/26) by 1 week to
      96% (25/26) by 1 month of age. Specimens obtained on the day of birth or the next
      day were the least likely to have detectable HIV DNA. CONCLUSIONS: The PCR assay
      of DBS specimens is a reliable tool for the early diagnosis of HIV infection and
      has important advantage over that of liquid blood DNA PCR and viral culture.
      These advantages include a lower volume of blood required for testing, increased
      safety, and ease of storage or transport of specimens. Thus DBS PCR is a useful
      test for clinical and epidemiologic tracking of infants at risk of HIV infection.

PMID- 8757571
TI  - Longitudinal, prospective analysis of dietary intake in children with cystic
      fibrosis.
AB  - OBJECTIVES: Prospective, 3-year longitudinal dietary intakes of 25 prepubertal,
      pancreatic-insufficient children with cystic fibrosis (CF) and mild lung disease,
      and the intakes of 26 control children were compared, and relationships among
      energy intake, nutritional status, and pulmonary function were determined. STUDY
      DESIGN: Intakes from 3-day weighed food records were compared with CF
      recommendations, recommended dietary allowances (RDA), and the recommendations of
      the Third National Health and Nutrition Examination Survey (NHANES III). Energy
      and nutrient intakes were analyzed by repeated-measures analysis of variance.
      RESULTS: Children with CF consumed more energy than control children (p = 0.025)
      in terms of calories per day, percentage of RDA by age and by age and weight,
      energy adjusted for fat malabsorption, and percentage of NHANES III
      recommendations. Energy intake was similar between boys and girls with CF. The
      percentage of energy from fat was greater (p = 0.0004) in the CF group (3-year
      mean, 33%) than in the control group. Height and weight z scores declined in the
      CF group (p <0.05) with time. Vitamin and mineral intakes were generally adequate
      in the CF group. CONCLUSIONS: The children in this sample did not consume the CF
      recommended intakes of 120% RDA for energy or a high-fat (40% of energy) diet.
      Energy intakes may be insufficient in this group to meet requirements for optimal
      growth.

PMID- 8757572
TI  - Differences in the hypothalamic-pituitary-adrenal axis of black girls and white
      girls.
AB  - After intravenous administration of ovine corticotropin-releasing hormone (CRH),
      the plasma corticotropin (ACTH) concentrations of adult black women and men are
      approximately twice as high as those of adult white women and men; however, there
      are no corresponding differences in cortisol response. To determine whether these
      differences in ACTH secretion are also present in prepubertal and early pubertal
      girls, we studied the hypothalamic-pituitary-adrenal axis of 19 black and 19
      white girls of normal weight (age 7 to 10 years) who were matched for body mass
      index, age, and socioeconomic status. Measures of cortisol's effects, including
      waist circumference, waist/hip ratio, and fasting insulin and glucose levels,
      were obtained and related to the ACTH and cortisol responses to 1 micrograms/kg
      CRH. There were no racial differences in waist circumference, waist/hip ratio,
      fasting glucose or insulin levels, baseline free or total plasma cortisol levels,
      baseline ACTH concentrations, or the plasma cortisol response to CRH. However,
      CRH-stimulated plasma ACTH concentrations, measured in a polyclonal radio
      immunoassay, were significantly greater in prepubertal and early pubertal black
      girls than in white girls at all time points between 15 and 90 minutes after
      administration of CRH (area under curve (AUC 1754 +/- 121 pmol/L/min in black
      girls vs 1304 +/- 124 pmol/L/min in white girls, p < 0.001). This difference was
      confirmed by an immunoradiometric assay believed to be specific for intact ACTH
      (AUC 1634 +/- 139 pmol/L/min in black girls vs 1224 +/- 104 pmol/L/min in white
      girls, p < 0.001). Neither ACTH AUC nor cortisol AUC was significantly correlated
      with body mass index in either black or white girls. We conclude that there are
      differences in the hypothalamic-pituitary-adrenal axis of prepubertal and early
      pubertal black and white girls similar to those found previously in adult women.
      The cause of these differences remains to be elucidated.

PMID- 8757573
TI  - Long-term follow-up of the Busselton six-year controlled trial of prevention of
      children's behavior disorders.
AB  - This study reports the follow-up in 1993 of 209 adults, aged 27 to 29 years, who
      as children had been enrolled in a controlled trial of the prevention of
      children's behavior disorders. One hundred four control subjects and 105 study
      subjects, representing 90% of the original cohort, responded to a questionnaire
      detailing their present social situation and habits, educational achievements,
      and emotional well-being. The study subjects overall reported significantly fewer
      neurotic symptoms (p <0.001) than the control subjects; the study women also
      reported significantly fewer depressive symptoms (p <0.001). A greater proportion
      of the study subjects, compared with control subjects, had undertaken a
      university degree or diploma (p <0.013), whereas fewer of the men had attended a
      school of technology (p <0.049). The study women were less likely to be obese, as
      defined by a body mass index of 25 or more (p <0.030). The study men and women
      tended to smoke less than their control subjects, though significant differences
      were not attained. These results in the experimental group reflected the behavior
      patterns recorded at 6 years of age, after initial preschool interventional
      therapy. It appears that the initial benefit obtained from active counseling of
      mothers about their preschool children's behavior may be long lasting, favorably
      affecting the individuals' psychologic well-being, educational achievements, and
      social habits as adults.

PMID- 8757575
TI  - Bone marrow transplantation in Hunter syndrome.
AB  - Hunter syndrome (mucopolysaccharidosis II) is a rare X-linked disorder of
      mucopolysaccharide metabolism that typically progresses to severe mental
      retardation and death by 18 years of age. A child with Hunter syndrome received
      an allogeneic bone marrow transplantation from an unaffected human leukocyte
      antigen-identical sibling at the age of 29 months without complications. Despite
      full and sustained engraftment now at 70 months after transplantation, the
      patient's neurocognitive abilities have continued to deteriorate. In this case,
      replacement of defective marrow-derived macrophages by bone marrow
      transplantation was not effective in preventing the neurologic progression of the
      disease in a child with the severe phenotype of Hunter syndrome.

PMID- 8757574
TI  - Routine use of fentanyl infusions for pain and stress reduction in infants with
      respiratory distress syndrome.
AB  - OBJECTIVE: To determine whether fentanyl infusions given to premature infants
      with respiratory distress syndrome reduce stress and improve long- and short-term
      outcome. METHODS: Twenty premature infants undergoing mechanical ventilation for
      respiratory distress syndrome were randomly assigned, in a double-blind fashion,
      to receive fentanyl by continuous infusion or a volume-matched placebo infusion.
      A behavioral state score was used to assess the infants' behavior. Cortisol and
      11-deoxycortisol levels were measured as physiologic markers of stress. Urinary 3
      methyl histidine/creatinine molar ratio was determined and the fractional
      excretion of urea was measured to assess catabolic state. Ventilatory indexes
      were recorded for each infant. RESULTS: Infants receiving fentanyl showed
      significantly lower behavioral state scores (p < 0.04) and lower heart rates (p <
      0.001) than those receiving placebo. 11-Deoxycortisol levels were lower in the
      fentanyl group on days 3, 4, and 5 of the study (p < 0.003). 3-Methyl
      histidine/creatinine ratios and fractional excretion of urea were not
      significantly different between the two groups. On the third day of the study,
      infants receiving fentanyl required a higher ventilator rate (p < 0.01), higher
      peak inspiratory pressures (p < 0.001), and higher positive end-expiratory
      pressure (p < 0.0001) than those receiving placebo. There was no difference in
      long-term outcome with respect to the incidence of bronchopulmonary dysplasia,
      intraventricular hemorrhage, or sepsis or with respect to the duration of
      ventilator use. CONCLUSIONS: Although there was a reduction in stress markers in
      the infants receiving fentanyl, we were unable to demonstrate an improvement in
      catabolic state or long-term outcome. In addition, the infants receiving fentanyl
      required higher ventilatory support in the early phase of respiratory distress
      syndrome than did those receiving placebo.

PMID- 8757576
TI  - Acceleration of retarded growth in children with Gaucher disease after treatment
      with alglucerase.
AB  - OBJECTIVES: The incidence and severity of growth retardation in children with
      type 1 Gaucher disease and the response to enzyme replacement therapy with
      alglucerase were studied. STUDY DESIGN: A retrospective analysis of growth in 99
      children and adolescents with type 1 Gaucher disease before treatment, and in 54
      of those subjects during treatment, was done. Growth was compared with gender,
      age, and dosage of replacement enzyme. RESULTS: Linear growth was normal in the
      first 1 to 2 years of life and then decelerated. Height was at or below the 5th
      percentile in 50% of all subjects immediately before treatment. The mean z score
      was -1.49 (95% confidence interval, -1.83 to -1.16), corresponding to the 6.8th
      percentile for height. Seventy-two percent were below the 50th percentile and 50%
      were at or below the 5th percentile for mid-parental height (p <0.001). One and
      one-half years after treatment was started, the estimated mean z score for all
      subjects was -1.01, which corresponds to the 16th percentile for height. Normal
      growth was achieved within 4 to 30 months in eight of nine subjects who were at
      or below the 5th percentile. It occurred only in those receiving higher doses (60
      to 120 U/kg per 4-week period) of alglucerase. There was a significant
      association between z scores for height before treatment and liver enlargement
      (r= 0.57; p < 0.01). CONCLUSIONS: Half of the subjects who manifest type 1
      Gaucher disease in childhood have growth retardation. Treatment with adequate
      amounts of modified enzyme replacement was effective in normalizing linear
      growth.

PMID- 8757577
TI  - A trial of the safety of inhaled beclomethasone in ventilator-treated neonates.
AB  - Fifteen neonates were studied to determine whether beclomethasone could be safely
      administered with a metered-dose inhaler to subjects with an endotracheal tube in
      place. Oxygen saturations and transcutaneous carbon dioxide values were monitored
      before, during, and after administration. We found significantly more episodes of
      desaturation to less than 85% before administration than after administration (p
      < 0.05). The transcutaneous carbon dioxide values increased 4 to 10 mm Hg during
      delivery (p < 0.02) but returned to baseline by 30 minutes.

PMID- 8757578
TI  - Allgrove syndrome: documenting cholinergic dysfunction by autonomic tests.
AB  - We describe two Hispanic adolescents with Allgrove syndrome (alacrima, achalasia,
      and sensorimotor polyneuropathy) in whom we documented cholinergic dysfunction by
      cardiovascular autonomic tests. Both patients had orthostatic hypotension and
      decreased heart rate variability.

PMID- 8757579
TI  - Hypoparathyroidism in mitochondrial trifunctional protein deficiency.
AB  - Mitochondrial trifunctional protein deficiency, a recently identified disorder of
      fatty-acid oxidation, may show characteristic features such as peripheral
      neuropathy, pigmentary retinopathy, and acute fatty liver degeneration in
      pregnant women with an affected fetus. We describe a patient with trifunctional
      protein deficiency whose clinical picture consisted of severe calcium and
      phosphate abnormalities caused by hypoparathyroidism.

PMID- 8757580
TI  - Recurrent "unexplained" scalp swelling in an eighteen-month-old child: an
      atypical presentation of angioedema causing confusion with child abuse.
AB  - In this article, we demonstrate that angioedema may atypically present with
      noninflammatory scalp or facial swelling without recurrence on other parts of the
      body and without urticaria. In a young child, such a presentation exclusively
      with recurrent "unexplained" swellings over different parts of the scalp could
      erroneously be misconstrued as child abuse (blunt head trauma).

PMID- 8757581
TI  - Semicircular lipoatrophy after intragluteal injection of benzathine penicillin.
AB  - A 3-year old girl had localized lipoatrophy after an intragluteal injection of
      benzathine penicillin G. No associated abnormalities were found.

PMID- 8757582
TI  - Allan Macy Butler (1894-1986).

PMID- 8757583
TI  - Nipple confusion--who is confused?

PMID- 8757584
TI  - Immune globulin G for treatment of opsoclonus-polymyoclonus syndrome.

PMID- 8757585
TI  - You gotta have heart.

PMID- 8757586
TI  - Hypophosphatemic rickets.

PMID- 8757587
TI  - Resistance to penicillin in Streptococcus pneumoniae.

PMID- 8757588
TI  - Macrosomic infants of nondiabetic mothers and insulin levels in cord blood.

PMID- 8757589
TI  - Treatment with intravenously administered immunoglobulins of the neuroblastoma
      associated opsoclonus-myoclonus.

PMID- 8757590
TI  - Value of parents' estimates of children's developmental ages.

PMID- 8757591
TI  - Beta-carotene supplementation in cystic fibrosis.

PMID- 8757592
TI  - Inhaled nitric oxide can cause severe systemic hypotension.

PMID- 8757593
TI  - Neurodevelopmental outcome in extracorporeal membrane oxygenation survivors.

PMID- 8757594
TI  - Congenital swallowing defects and rehabilitation in infants.

PMID- 8757595
TI  - Oxygen delivery: nasopharyngeal catheter or nasal prongs?

PMID- 8757596
TI  - Twin-to-twin transfusion syndrome.

PMID- 8757597
TI  - Granulocyte colony-stimulating factor and congenital neutropenia--risk of
      leukemia?

PMID- 8757598
TI  - Identification through bioinformatics of cDNAs encoding human thymic shared Ag
      1/stem cell Ag-2. A new member of the human Ly-6 family.
AB  - The Ly-6 family of cell surface molecules includes many members that have been
      characterized in the mouse. Until recently, very few Ly-6 family members had been
      described in the human. A significant development with important implications for
      novel gene discovery has been the growth of the public Expressed Sequence Tag
      (EST) database. Here we report that, through the application of bioinformatics
      analysis to the dbEST database, we obtained the sequence of human TSA-1/SCA-2, a
      new member of the human Ly-6 family. In addition, we identified full-length
      clones encoding this molecule as well as expression data in various tissues.
      Sequencing of the clones identified this way confirmed the sequence predicted
      through bioinformatics. This study constitutes an example of the application of
      bioinformatics to the analysis of the recently expanded databases for the
      identification of genes of potential importance in the immune system.

PMID- 8757599
TI  - HIV-1-Tat protein promotes chemotaxis and invasive behavior by monocytes.
AB  - Monocytes are susceptible to HIV infection and to activation by a regulatory gene
      product of the HIV genome, HIV-Tat. Recently, we have demonstrated that treatment
      with HIV-Tat up-regulates monocyte adhesion to the endothelium and increases
      metalloproteinase production. in the present study, we have examined the ability
      of the HIV-Tat protein to alter the migratory and invasive behavior of monocytes.
      Monocytes pretreated for 24 h with 10 ng/ml HIV-Tat exhibited enhanced migratory
      behavior compared with untreated monocytes in chemotaxis assays, both in the
      absence of a chemoattractant as well as in response to FMLP. in addition, HIV-Tat
      itself induced the migration of both untreated and HIV-Tat pretreated monocytes.
      Checkerboard analysis showed that monocytes migrated in response to an HIV-Tat
      concentration gradient, thus confirming the chemotactic characteristics of the
      HIV-Tat protein. Pretreatment of monocytes with 10 ng/ml HIV-Tat for 24 h also
      increased their ability to invade reconstituted extracellular membrane (Matrigel)
      coated filters by 5-fold in the absence of chemoattractant. The presence of FMLP
      or HIV-Tat further enhanced invasion by both untreated and HIV-Tat-pretreated
      monocytes by more than 10-fold. Monocyte invasion was partially inhibited by the
      inclusion of anti-beta integrin Ab or tissue inhibitor of metalloproteinase
      (TIMP). Thus, for the first time, we present evidence that HIV-Tat can enhance
      the chemotactic and invasive behaviors of monocytes and propose an active role
      for HIV-Tat in the recruitment of monocytes into extravascular tissues, a process
      which may contribute to the destruction of tissues and cellular architecture
      often seen in patients with acquired immunodeficiency syndrome.

PMID- 8757600
TI  - CD8(+) T cell-mediated spontaneous diabetes in neonatal mice.
AB  - Transgenic mice that express the influenza virus hemagglutinin (HA) on pancreatic
      islet beta cells (ins-HA) demonstrate tolerance of HA even after immunization
      with influenza virus. Surprisingly, when Ins-HA mice were mated with a transgenic
      mouse expressing a TCR specific for an epitope of HA that is restricted by MHC
      class I H-2Kd (Clone-4 TCR), the resulting double transgenic (Ins-HA x Clone-4
      TCR)F1 neonates developed spontaneous autoimmune diabetes immediately after birth
      and died within 10 days. This represents a unique situation in which all
      safeguards within the immune system that normally maintain tolerance of self
      antigens in the neonate are insufficient.

PMID- 8757601
TI  - Chemokine expression by intraepithelial gamma delta T cells. Implications for the
      recruitment of inflammatory cells to damaged epithelia.
AB  - T cells expressing gamma delta TCR may have evolved to recognize Ag in a
      different manner as well as perform a broader set of functions than T cells with
      alpha beta TCR. In this study, we tested the hypothesis that dendritic epidermal
      T cells (DETC) bearing the invariant V gamma 3V delta 1 TCR may be able to signal
      the migration of peripheral alpha beta T cells to the epidermis by secreting
      specific chemokines. Expression of macrophage inflammatory protein (MIP)-1 alpha,
      MIP-1 beta, RANTES, and lymphotactin was inducible in DETC 7-17 cells, whereas
      mRNA for monocyte chemoattractant protein (MCP)-1 could not be detected.
      Strikingly, lymphotactin was the most abundant chemokine produced by activated
      DETC 7-17 cells. Activated primary DETC cultures also produced copious amounts of
      lymphotactin mRNA. Similarly, freshly isolated and activated intestinal
      intraepithelial T cells (i-IEL) with gamma delta TCR expressed high levels of
      lymphotactin mRNA. In contrast, lymphotactin mRNA was present in activated spleen
      gamma delta T cells at low basal levels. Migration of CD8+ T cells induced by
      culture supernatants from stimulated DETC 7-17 cells was strongly reduced in the
      presence of a neutralizing anti-lymphotactin antiserum and to a lesser extent by
      neutralizing anti-MIP-1 alpha, anti-MIP-1 beta, or anti-RANTES antiserum. The
      presence of lymphotactin in supernatants from activated DETC 7-17 cultures was
      directly demonstrated by Western blot analysis. These observations are consistent
      with a model in which gamma delta IEL play an active multi-faceted role in the
      maintenance of epithelia homeostasis.

PMID- 8757602
TI  - Ligation of MHC class I molecules on peripheral blood T lymphocytes induces new
      phenotypes and functions.
AB  - Microgram concentrations of immobilized anti-MHC class I (MHC-I) Ab induced
      proliferation of resting CD3+ T cells from peripheral blood. In contrast, soluble
      Ab did not activate T cells. Exposure of T cells to immobilized anti-MHC-I Ab for
      only 24 h was followed by proliferation and development of T cell-mediated
      cytotoxicity. Immediately following MHC-I ligation, the T cells responded with
      increased protein tyrosine phosphorylation, with new bands appearing in the SDS
      PAGE. Exposure of T cells to immobilized anti-MHC-I Ab for 24 h induced an
      increased surface expression of the TCR/CD3 and CD28 molecules. MHC-I-induced
      proliferation of purified T cells was dependent on cellular interactions with non
      T cells. Under certain conditions, in which MHC-I was ligated by picogram
      concentrations of immobilized anti-MHC-I Ab, anti-TCR/CD3 Ab-induced
      proliferation of T cells was strongly inhibited. These data clearly demonstrate
      that ligation of the MHC-I complex on T cells may induce both positive and
      negative signals. Since the physiologic ligands for MHC-I molecules are TCR and
      the CD8 molecules, our data may suggest that MHC-I molecules are instrumental in
      cellular interactions between T cells.

PMID- 8757603
TI  - CTL recognition of an altered peptide associated with asparagine bond
      rearrangement. Implications for immunity and vaccine design.
AB  - The extent to which peptides containing chemically and post-translationally
      modified amino acid side chains are recognized by primed CTL has not been clearly
      defined. We report on the CTL recognition of a MHC class I-restricted peptide
      containing a cyclized asparagine (succinimide) residue. This modification of the
      asparagine side chain is a common intermediate structure during deamidation,
      isomerization, and bond rearrangements of amide-containing amino acids and also
      occurs as a side reaction in peptide synthesis. The CTL specifically recognized
      the succinimide-containing peptide showing only weak cross-reactivity at high
      concentrations of the parent peptide containing unmodified asparagine. Similarly,
      CTL raised against the parent peptide did not recognize the succinimide
      derivative of this peptide. Naturally processed forms of these structures are
      likely to occur given the importance and frequency of deamidation both in vitro
      and in vivo. Moreover, since succinimide intermediates of deamidated peptides can
      occasionally be very stable, these peptides have the potential to act as altered
      self-Ags with significant implications for autoimmunity. In addition, unwanted
      and potentially hazardous specificities may be elicited when using synthetic
      peptides in subunit vaccines in which succinimide residues may form spontaneously
      during storage or chemical synthesis.

PMID- 8757604
TI  - Cellular and molecular factors that regulate the differentiation and apoptosis of
      germinal center B cells. Anti-Ig down-regulates Fas expression of CD40 ligand
      stimulated germinal center B cells and inhibits Fas-mediated apoptosis.
AB  - To investigate the molecular and cellular mechanisms underlying the selection,
      differentiation, and apoptosis of germinal center (GC) B cells, we have
      established a culture system containing a follicular dendritic cell (FDC) line,
      HK. The mAb, 3C8, which is specific to HK cells and recognizes dendritic network
      in the GC, was developed and provided additional evidence that HK cells are
      related to FDC by sharing a unique surface Ag. The roles for CD40 ligand (CD40L)
      and T cell-derived cytokines in the differentiation of GC B cells were
      investigated in our culture system. We show that there are two distinct stages of
      GC B cell differentiation. In the early stage, GC B cells undergo spontaneous
      apoptosis unless they are stimulated by CD40L. In the secondary stage, IL-10
      directs GC B cell differentiation toward the generation of plasma cells, while
      the absence of IL-10 stimulation leads to the generation of memory B cells. The
      major function of CD40L was found in the enhancement of cell recovery and the
      augmentation of memory B cell generation. Although GC B cells are Fas+, GC B
      cells are at first resistant to, but then become sensitive to, anti-Fas killing
      after 24 h in culture with CD40L, which coincides with the gradual increase in
      Fas expression on GC B cells. Furthermore, anti-Ig down-regulated Fas expression
      on CD40L-stimulated GC B cells, suggesting that Ag receptor engagement down
      regulates Fas expression and prevents Fas-mediated apoptosis of GC B cells. Our
      data imply that GC T cells have an important role in the differentiation and
      apoptosis of GC B cells. GC T cells expressing both CD40L and Fas ligand have a
      dual function on GC B cells, helper or killer, depending on the status of target
      B cells. In the early stage, GC T cells stimulate the extensive proliferation of
      GC B cells, ensuring a large repertoire of B cells for selection. In the later
      stage, GC T cells kill B cells via Fas-Fas ligand interactions unless GC B cells
      are positively selected by Ags present on FDC.

PMID- 8757605
TI  - Targeting signal and subcellular compartments involved in the intracellular
      trafficking of HLA-DMB.
AB  - Evidence suggests that peptide loading onto MHC class II molecules occurs in a
      specialized late endocytic compartment (MIIC) where HLA-DM predominantly resides
      and in which MHC class II transiently accumulates before transport to the cell
      surface. We examined the targeting signals and compartments involved in the
      intracellular trafficking of human HLA-DM by expressing hybrid molecules
      comprising the cytoplasmic domain of DMB and luminal and transmembrane domains of
      CD8 in HeLa cells. A tyrosine-based tetrapeptide motif present in the cytoplasmic
      domain of DMB targeted hybrid molecules to intracellular vesicles. Mutation of
      the tyrosine residue to alanine resulted in redistribution of hybrid molecules to
      the cell surface. Correct intracellular targeting of HLA-DM was crucial for
      normal function in B cells. Immunoelectron microscopy on ultrathin cryosections
      showed that CD8-DMB molecules accumulated in late endocytic compartments sharing
      characteristics with lysosomes, like MHC class II compartments in APCs. Thus far,
      the exit of DMB from the Golgi complex has not been elucidated. Interestingly, we
      found that although the mannose 6-phosphate receptor and CD8-DMB contain similar
      tyrosine signals, no co-localization was observed in the trans-Golgi network,
      suggesting that these proteins are differentially sorted at this site. Co
      transfection of CD8-DMB, HLA-DR alpha, HLA-DR beta, and an invariant chain
      revealed that HLA-DR molecules accumulated together with CD8-DMB in these
      lysosomal compartments. The similarity of these lysosomal-like compartments in
      wild-type and transfected cells suggests that they are part of the normal
      endocytic pathway in non-APCs.

PMID- 8757606
TI  - Activation of murine lymphocytes by lipopolysaccharide incorporated in fusogenic,
      reconstituted influenza virus envelopes (virosomes).
AB  - We have studied the in vitro activation of murine lymphocytes with LPS
      incorporated in the membranes of both phospholipid vesicles (liposomes) and
      vesicles composed of fusogenic, reconstituted influenza virus envelopes
      (virosomes). The incorporation of Salmonella minnesota rough-LPS in liposomes
      reduced the potency of LPS to stimulate splenocyte proliferation and cell surface
      kappa-light chain expression on 70 Z/3 pre-B cells by over 100-fold. Salmonella
      minnesota rough-LPS inserted into virosomes was at least 10-fold more potent than
      free LPS, both when prebound virosomes were allowed to be taken up by the cells
      at neutral pH and when the virosomes were fused into the plasma membrane by low
      pH treatment. Inactivation of the virosomes by low pH pretreatment reduced the
      potency of the virosomal LPS to the level of liposome-incorporated LPS. The
      association of the various LPS forms with the cells was quantitated using radio
      iodinated LPS. Correcting for uptake, virosomal LPS remained 2- to 10-fold more
      potent than free LPS in stimulating B lymphocytes and at least 100-fold more
      active than liposomal LPS or fusion-inactivated virosomes. After low pH-induced
      fusion with the plasma membrane, the majority (80%) of the prebound virosomes had
      fused with the cells, compared with about 8% after neutral uptake. From these
      results we conclude that LPS inserted into the plasma or endosomal membranes
      efficiently activates murine lymphocytes. The fusion data suggest that the
      incorporation into endosomal membranes might be a more effective stimulus.

PMID- 8757607
TI  - T cell recognition and tolerance of antibody diversity.
AB  - The capacity of B cells to self-present their Ab variable regions in the context
      of class II MHC structures suggests a potential regulatory problem. If T cells
      were able to recognize self-presented Ab, then T cell help might be delivered to
      B cells independently of a foreign carrier epitope, resulting in a chronic state
      of unregulated Ab synthesis. For this reason, we have proposed that T cells
      normally attain a state of tolerance to Ab V region diversity. Here, we tested
      this idea by performing direct immunizations with unmutated isologous mAb. We
      also identified and analyzed epitopes recognized by class II MHC-restricted T
      cell hybridomas that were originally generated against two physiologically
      mutated isologous mAb. Our results indicate that the class II MHC-restricted T
      cell repertoire is tolerant of germ-line-encoded Ab diversity and that the
      physiologic somatic hypermutation process creates immunogenic epitopes in Ab V
      regions, in some cases by producing class II MHC-binding peptides. In agreement
      with these findings, we found that germ-line-encoded Ab V regions are presented
      by endogenous splenic APC at a level that is physiologically significant.

PMID- 8757608
TI  - Different CD40-mediated signaling events require distinct CD40 structural
      features.
AB  - Signals delivered to B cells through CD40 are critical to the development of
      humoral immune responses. In this study we characterize regions of the 62-amino
      acid cytoplasmic domain of human CD40 (hCD40) that are essential for signal
      transduction and examine the functional consequences of mutations in these
      regions. A panel of mutant hCD40 molecules was stably expressed in mouse B cell
      lines and tested for its ability to stimulate Ab secretion, homotypic adhesion,
      and increased surface expression of B7, Fas, CD23, LFA-1, and intracellular
      adhesion molecule-1. Our results indicate that CD40 contains at least two major
      signaling determinants in the cytoplasmic domain: one disrupted by a truncation
      of 22 amino acids, and a second disrupted by the removal of 10 additional amino
      acids. The second determinant includes threonine 234, a residue previously shown
      to be important in CD40 signal transduction. Our functional analysis of alanine
      and serine substitutions at position 234 indicates that phosphorylation of this
      residue may be important for full CD40 signaling activity.

PMID- 8757609
TI  - bcl-2 alters the antigen-driven selection of B cells in mukappa but not in mu
      only Xid transgenic mice.
AB  - A point mutation in the pleckstrin homology domain of the mouse Bruton's tyrosine
      kinase (btk) gene results in an X-linked immune defect, Xid, characterized by
      immunologic unresponsiveness to polymeric carbohydrate Ags. In Xid mice, B cells
      specific for phosphocholine (PC) do not develop in peripheral lymphoid tissues
      because they either fail to be positively selected from the marrow or they are
      clonally deleted via an Ag-driven, receptor-mediated process. Overexpression of
      the bcl-2 gene allows PC-specific B cells to survive and mature in Xid mukappa
      anti-PC transgenic mice, but PC-specific B cells are not rescued by bcl-2 in Xid
      mu-only transgenic mice. The failure of bcl-2 to rescue PC-specific B cells, in
      mu-only transgenic mice suggests that either it does not correct the btk defect
      in the Ag-driven selection process that occurs in pre-B cells and/or in very
      immature B cells or that a btk-dependent proliferative phase is required for the
      selection and amplification of the PC-specific B cells in mu-only transgenic
      mice. The rescue of PC-specific B cells in mukappa transgenic mice indicates that
      bcl-2 can alter receptor-mediated B cell selection at late stages in B cell
      development. The rescued PC-specific B cells in Xid male mice do not exhibit an
      altered proliferation profile in response to B cell-stimulating agents compared
      with B cells from unmanipulated Xid mice; thus, they fail to respond to soluble
      anti-mu, or PC-dextran, but they proliferate in response to PC, anti-mu, or anti
      id conjugated to Sepharose.

PMID- 8757610
TI  - Anergy-associated T cell antigen presentation. A mechanism of infectious
      tolerance in experimental autoimmune encephalomyelitis.
AB  - CD4+ T cells promote immune responses against foreign Ags while actively
      suppressing responses against self Ags. To address how CD4+ T cells ensure self
      tolerance, we focused on two CD4+ T helper cells specific for myelin basic
      protein (MBP). GP2.E5/R1 T cells recognized rat MBP (RMBP) as a partial agonist
      and mediated mild experimental autoimmune encephalomyelitis (EAE), whereas R2 T
      cells recognized RMBP with full efficacy and mediated severe EAE. GP2.E5/R1 T
      cells were more susceptible to anergy induction than R2 T cells. Anergic
      GP2.E5/R1 T cells lacked proliferative reactivity, but expressed both I-A
      glycoproteins and high levels of radioresistant APC activity. During induction of
      anergy, these T cells acquired the ability to present MBP. In a separate
      subsequent culture without further addition of Ag, anergic GP2.E5/R1 T cells
      elicited full proliferative and IL-2 production responses by R2 T cells. Unlike
      activations induced via irradiated splenocytes, irradiated anergic T cells
      elicited anergy in R2 T cells in the form of a postactivational phase of
      nonresponsiveness. Anergic GP2.E5/R1 T cells not only transferred anergy to
      pathogenic R2 T cells in vitro, but these anergic T cells also transferred
      resistance to EAE in Lewis rats subsequently challenged with guinea pig MBP in
      CFA. Antagonistic signaling by autologous RMBP was more tolerogenic than that of
      guinea pig MBP in both in vitro and in vivo models of infectious anergy. We
      conclude that in the presence of tolerogenic mAb, antagonistic signaling by a
      self protein elicited the coordinate expression of anergy and T cell-mediated APC
      activity as a mechanism for the genesis and spread of infectious tolerance.

PMID- 8757611
TI  - Cross-reactivity of T cell lines and clones to beta-lactam antibiotics.
AB  - To clarify on a molecular level the specific T cell response to haptens like
      penicillin G, we generated T cell lines and clones from penicillin-allergic
      patients. Two types of beta-lactam reactivity of T cells could be delineated: one
      group of patients showed a rather restricted specificity, as the penicillin
      elicited T cell lines generated from such donors proliferated only to the
      stimulating penicillin, but not to other beta-lactam antibiotics nor to
      cephalosporines, even if the side chain was identical. This indicates that the
      penicilloyl structure together with the side chain was recognized by these T
      cells. The second group comprised patients with more broadly reactive T cells, as
      they were restimulated by penicillin G as well as by related penicillins like
      amoxicillin or ampicillin, but not cephalosporines. This indicates that the
      penicilloyl structure, a common motif of penicillins, was important for T cell
      recognition. Clones generated from a broadly reactive patient confirmed this
      heterogeneity, as either monospecific or broadly specific T cell clones could be
      identified. This broad or very restricted pattern of T cell reactivity was
      reflected in the use of TCR Vbeta-chains: while the broadly reactive T cell lines
      showed a heterogenous TCR usage, the highly restricted T cell lines showed an up
      regulation of one TCR Vbeta-chain. Thus, our data suggest that the outgrowth of T
      cells bearing a certain TCR Vbeta may be a sign of a limited cross-reactivity.

PMID- 8757612
TI  - Cyclic adenosine 3',5'-monophosphate increases the open probability of potassium
      channels in activated human T cells.
AB  - In the present report we describe a cAMP-responsive K channel in activated human
      T cells. Single channel events were recorded using the patch-clamp technique in
      cell-attached-patch configuration. The channel was K selective, as determined by
      reversal potentials under different K gradients, and displayed voltage
      independent gating. When the applied potential (Vp) was equal to zero, the
      conductance of the channel was 21.8 +/- 0.9 pS with 150 mM K in the electrode.
      Typical patches contained between two and seven channels that were relatively
      quiet, or silent, before agonist stimulation. Adenosine (20-30 microM) increased
      the average open time probability from 0.017 +/- 0.008 to 0.108 +/- 0.054 over a
      period of 108 s. Subsequent addition of the phosphodiesterase inhibitor Ro 20
      1724 (0.5 mM) increased the probability of being in the open state to 1.155 +/-
      0.407 over a period of 180 s. Channel kinetics were well described by assuming
      two open and two closed states. Exponential time constants for the open states
      were 0.51 +/- 0.06 and 4.34 +/- 0.31 ms, and closed state time constants were
      0.58 +/- 0.05 and 10.1 3 +/- 2.32 ms. In addition, extracellular ATP (0.3-1.0 mM)
      decreased channel activity. Moreover, Rp-cAMP (0.5-1.0 mM), an antagonist that
      specifically blocks the ability of cAMP to bind and activate protein kinase A,
      failed to inhibit adenosine- and Ro 20-1724-induced increases in channel
      activity, implying a direct action of cAMP on channel gating.

PMID- 8757613
TI  - Thymocyte cell fate alteration by high levels of CD8alpha is independent of CD8
      lck association.
AB  - CD8 expression on the surface of developing thymocytes is essential for the
      positive selection and maturation of CD8 single positive T cells. CD8 is
      physically associated with the cytoplasmic tyrosine kinase, p56lck and, in
      addition to increasing the avidity between the TCR and MHC/peptide complex, may
      transduce intracellular signals. Here we address the extent to which the
      requirement for CD8 in thymocyte selection depends on its capacity to signal vs
      its contribution to avidity. We have previously reported that elevated levels of
      CD8alpha can alter the fate of developing 2C TCR+ thymocytes from positive to
      negative selection in H-2b mice. We show here that the fate of 2C TCR thymocytes
      overexpressing a mutant form of CD8alpha that does not bind to p56lck is the same
      as that of thymocytes overexpressing the wild-type CD8alpha-chain. This finding
      demonstrates that, for a TCR-MHC system in which the level of CD8alpha is the
      deciding factor in cell fate, negative selection does not require increased CD8
      dependent signaling through p56lck. We have also found that highly elevated
      levels of CD8alpha expression (10-fold) block thymocyte maturation in both
      CD8alpha single and CD8alpha/HY TCR double transgenic mice. Although these may be
      additional examples of CD8alpha overexpression altering cell fate from positive
      to negative selection, we present arguments in favor of the interpretation that
      high levels of CD8alpha actually may block positive selection.

PMID- 8757614
TI  - Lyphocyte migration in L-selectin-deficient mice. Altered subset migration and
      aging of the immune system.
AB  - Lymphocyte trafficking across high endothelial venules (HEV) of peripheral lymph
      nodes (PLN) is dependent upon lymphocyte expression of L-selectin. Mice that lack
      this adhesion molecule provide an opportunity to determine the long-term role of
      L-selectin-mediated migration in the maintenance of leukocyte subpopulations. HEV
      in L-selectin-deficient mice were phenotypically, morphologically, and
      functionally comparable with wild-type mice, although there was a 70 to 90%
      reduction in the number of lymphocytes within PLN. These lymphocytes most likely
      entered PLN through the afferent lymphatics, since they did not migrate into PLN
      of normal mice during short-term homing experiments. The impaired trafficking of
      lymphocytes across PLN-HEV resulted in the accumulation of memory
      (CD18highCD44high) lymphocytes within PLN, and also altered the distribution of
      lymphocyte subpopulations within other tissues. Specifically, a 30 to 55%
      increase in splenic cellularity occurred due to increases in both naive and
      memory lymphocytes. Circulating lymphocyte numbers or subpopulations were not
      altered in young L-selectin-deficient mice, but circulating monocyte numbers were
      increased nearly threefold. In contrast, older L-selectin-deficient mice had
      disproportionate increases of both naive and memory CD4+ T cells present within
      spleen and blood. These results and the finding that memory lymphocytes in wild
      type mice expressed L-selectin demonstrate a requirement for L-selectin in the
      regulation of memory lymphocyte migration. Therefore, L-selectin-dependent
      pathways of lymphocyte migration are important for the normal migration of both
      naive and memory lymphocytes.

PMID- 8757615
TI  - Activation of the Na(+)/H(+) antiporter, Na+/HCO3(-)/CO3(2-) cotransporter, or
      Cl(-)/HCO3(-) exchanger in spontaneous thymocyte apoptosis.
AB  - This study was undertaken to define the role of ion transporters on the apoptosis
      of thymocytes. Culture conditions, such as the ionic strength of NaCl, Ca2+, the
      buffer system (HCO3-/CO2), and the pH, could influence the spontaneous apoptosis
      of thymocytes. Depletion of NaCl in the culture medium either delayed or
      completely inhibited the apoptotic process of thymocytes, while its restoration
      led to a dose-dependent apoptosis. A high concentration (100 microM) of Ca2+
      induced thymocyte apoptosis in the nominal absence of NaCl, whereas a low
      concentration (10 microM) enhanced apoptosis in the presence of 138 mM NaCl.
      Thymocytes had a higher spontaneous apoptotic rate in cultures without HCO3-/CO2
      than in those with HCO3-/CO2. The thymocyte apoptosis completely ceased in medium
      at pH 6.0 and was considerably enhanced at pH 7.6. Intracellular pH, determined
      with the pH-sensitive bis-carboxyethyl carboxyfluorescein probe, was higher in
      apoptotic thymocytes than in nonapoptotic cells. Spontaneous apoptosis occurred
      in cells with alkaline intracellular condition, whereas it was considerably
      retarded in cells under acidified conditions. Amiloride analogue, including 5
      (N,N-dimethyl)-amiloride (Na+/H+ antiporter), 4,4'-diisothiocyanato-stilbene-2,2'
      disulfonic acid (Cl-/HCO3- exchanger), and 4-acetamido-4'-isothiocyanato-stilbene
      2,2'-disulfonic acid (Na+/HCO3-/CO3(2-) cotransporter), inhibited the spontaneous
      thymocyte apoptosis. In contrast, neither cycloheximide nor actinomycin D had the
      same effect. In addition, thymocyte apoptosis was enhanced by PMA, but inhibited
      by forskolin. Taken together, thymocytes cultured in vitro underwent apoptosis
      with increased intracellular pH via activation of Na+/H+ antiporter, Na+/HCO3
      /CO3(2-) cotransporter, or Cl-/HCO3- exchanger. This process does not require de
      novo protein synthesis.

PMID- 8757616
TI  - Nonsecretory apoptotic killing by human NK cells.
AB  - We defined a novel constitutive mechanism of cell-mediated cytotoxicity, utilized
      by nonactivated human peripheral blood NK cells against a variety of tumor cell
      targets resistant to secretory (i.e., perforin/granzyme-mediated) NK cell
      killing. Untreated NK cells rapidly induced membrane damage and necrosis in K562
      target cells (as determined by 51Cr release assay and confirmed by transmission
      electron microscopy; TEM), in the absence of DNA fragmentation and apoptosis (as
      assessed by [3H]thymidine release assay and TEM). Chelation of extracellular Ca2+
      or paraformaldehyde fixation completely abrogated NK cell secretory activity and
      necrotic killing. In contrast, NK cells with either normal or impaired secretion
      consistently exhibited cytotoxicity against a wide variety of solid tumor cell
      lines in 1-h [3H]thymidine release, but not in 4-h 51Cr release, assays. Thus,
      the cytotoxicity was attributable to a nonsecretory, cell membrane-mediated
      mechanism. It appeared to selectively induce DNA fragmentation and apoptosis
      without plasma membrane damage and necrosis. This was further demonstrated by a
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and
      confirmed by TEM. Among defined populations of immune cells, only NK cells showed
      an inherent ability to rapidly induce apoptotic death in solid tissue-derived
      malignant cells. This study demonstrates that NK cells are unique immune cells
      constitutively endowed with multiple mechanisms of destroying abnormal cells.

PMID- 8757617
TI  - IL-12 induces human T cells secreting IL-10 with IFN-gamma.
AB  - A clear differentiation of Th1 and Th2 cytokine-secreting subsets in humans has
      not yet been defined. To further examine cytokine-directed differentiation of
      human T cell responses to both exogenous and autoantigens, we generated 346 short
      term T cell lines at limiting dilutions from six normal individuals to tetanus
      toxoid and myelin basic protein in the presence of IL-2 with or without the
      addition of IL-12 and anti-IL-4 mAb. T cell lines were examined for [3H]thymidine
      incorporation and cytokine secretion of IFN-gamma, IL-4, and IL-10. After culture
      in the presence of IL-12 and anti-IL-4 mAb, the predominant T cell response to Ag
      stimulation was simultaneous secretion of IL-10 and IFN-gamma. The concomitant
      secretion of IL-10 and IFN-gamma by T cells was confirmed by stimulating lines in
      the absence of APCs with plate-bound anti-CD3 mAb after two rounds of Ag-specific
      stimulation. Moreover, IL-12 enhanced IL-10 and IFN-gamma production in a myelin
      basic protein-reactive T cell clone, demonstrating that a differentiated T cell
      clone could be induced to secrete both cytokines. The addition of a neutralizing
      anti-IFN-gamma Ab to cultures with IL-12 and anti-IL-4 mAb during the generation
      of tetanus toxoid-reactive lines had no effect on the induction of IL-10 and IFN
      gamma secretion, indicating that IL-12 and not IFN-gamma was responsible for the
      induction of this subset of T cells. Thus, in human T cells, IL-12 induces
      concomitant secretion of IL-10 and IFN-gamma.

PMID- 8757618
TI  - Transduction of specific inhibition of HuT 78 human T cell chemotaxis by type I
      vasoactive intestinal peptide receptors.
AB  - The major immunoregulatory effects of vasoactive intestinal peptide (VIP) are
      mediated by structurally distinct types I (VIPR1) and II (VIPR2) G protein
      associated receptors on some T cells, B cells, and macrophages. Identification of
      the separate immunologic activities of each type of VIPR has been complicated by
      the usual expression of only VIPR2 or of VIPR1 and VIPR2 together by most human T
      cells obtainable in sufficient number for functional analyses. The results of
      reverse-transcription PCR, Western blot, and [125I]VIP-binding studies have
      established that HuT 78 cultured human lymphoma T cells bear a mean of 75,000
      VIPR1s per cell with a mean Kd of 3.3 nM, which transduce mean maximal increases
      in intracellular concentration of cAMP of 2.1-fold (ED50 = 72 nM), but no VIPR2s.
      HuT 78 T cells, in contrast to T cells that express VIPR2, did not respond to VIP
      by chemotaxis through micropore filters without or with a top layer of basement
      membrane-like Matrigel. Matrix metalloproteinase (MMP)-dependent in situ cleavage
      of [3H]type IV human collagen in the layer of Matrigel by HuT 78 T cells also was
      not stimulated by VIP. In contrast, IL-4 and TNF-alpha both stimulated HuT 78 T
      cell chemotaxis and in situ MMP activity at respective optimal concentrations
      ranging from 3 x 10(-10) M to 3 x 10(-9) M and 10(-10) M to 3 x 10(-10) M. VIP
      inhibited significantly HuT 78 T cell chemotaxis through Matrigel in response to
      both IL-4 and TNF-alpha, as a result of suppression of both chemotactic mobility,
      assessed by migration through micropore filters without Matrigel, and in situ MMP
      activity. The transduction of opposite effects of VIP on T cell migration through
      a model basement membrane by VIPR1 and VIPR2 suggests that the net chemotactic
      response of most T cells to VIP is determined by the VIPR2/VIPR1 ratio and that
      the predominant expression of VIPR1 would stabilize T cell populations in
      lymphoid follicles and tissue infiltrates.

PMID- 8757619
TI  - Identification of a novel regulatory region critical for expression of the RANTES
      chemokine in activated T lymphocytes.
AB  - The RANTES chemokine is a T cell-expressed, proinflammatory cytokine recently
      implicated as a suppressive agent of HIV replication. We have identified tandem
      kappaB-like sequences within the promoter for RANTES that are critical for RANTES
      promoter-reporter gene activity in both the T cell tumor line Hut78 and in PHA
      activated PBL. This region binds not only Rel family members (including p50-p65
      heterodimers and p50-p50 homodimers) but also non-Rel factors up-regulated in PBL
      3 to 5 days following activation. The expression of these "late" expressed
      nuclear factors correlates with an up-regulation of RANTES message found at this
      point in T cell activation. These factors are also constitutively expressed in
      functionally mature CD8+ T cells. We hypothesize that these apparently novel
      proteins are responsible in part for the temporal regulation of RANTES seen in
      peripheral blood T cells and represent a component of transcriptional regulatory
      machinery newly expressed at this "late" stage of peripheral T cell development.

PMID- 8757620
TI  - Differential regulation of c-Rel translocation in activated B and T cells.
AB  - c-Rel induction in activated lymphocytes is suppressed by the immunosuppressive
      drug, FK506. Here we show that FK506-suppressible, delayed c-Rel induction is
      similar in B and T cells and is regulated by mRNA production. In contrast, rapid
      nuclear translocation of pre-existing cytoplasmic c-Rel occurs only in B cells,
      but not in T cells. Analysis of I-kappaBalpha and -beta in these cells showed
      that both I-kappaBalpha and I-kappaBbeta were rapidly degraded in response to
      stimulation in B cells, but only I-kappaBalpha was affected in T cells. These
      observations suggest that 1) different Rel proteins in the same cell may be
      sequestered in the cytoplasm differently, 2) the sequestration mechanism is cell
      type specific, and 3) differential sensitivities of I-kappaBalpha and beta in B
      and T cells may regulate, in part, the rapid response of family members. We
      propose that subunit-specific and cell-specific regulation of nuclear
      translocation may help determine the varied cellular responses to different
      stimuli.

PMID- 8757621
TI  - Chicken monoclonal antibody isolated by a phage display system.
AB  - A method for obtaining chicken mAb using a phage display system was established.
      Chickens were hyperimmunized with murine serum albumin, and polyadenylated RNA
      was extracted from their spleen cells. cDNA of V regions of heavy or lambda-chain
      genes were obtained by reverse transcription-PCR using a pair of newly designed
      primers. A phage display library of 1.4 x10(7) clones expressing the chicken Ab
      variable region as a single chain was constructed. The library was panned three
      times against the Ag, then screened by ELISA. Of a number of Ag-binding clones,
      five mAb were identified by DNA sequencing. The specificity of these mAb for
      serum albumin of various species was examined by ELISA. The results showed
      different degrees of cross-reactivity to rat serum albumin, but not to other
      albumin. This method provides a procedure for efficiently generating specific
      chicken mAb against murine proteins and against the proteins of other mammals,
      whose amino acid sequences are highly conserved in mammalian species. The
      nucleotide sequences of lambda-chains revealed components to develop
      diversification of chicken Ab molecules. Four to seven pseudogene sequences were
      found per lambda-chain, which are regarded as donors in gene conversion for
      preimmune repertoire formation. A total of 28 nucleotide substitutions, which may
      be somatic hypermutations in Ag-driven affinity maturation but could also be
      errors introduced during gene conversion or polymorphic residues, were found in
      five lambda-chains.

PMID- 8757622
TI  - The presentation of class I and class II epitopes of listeriolysin O is regulated
      by intracellular localization and by intercellular spread of Listeria
      monocytogenes.
AB  - The hemolysin, listeriolysin 0 (LLO), produced by Listeria monocytogenes is both
      a virulence factor and an immunodominant Ag. In this study, we investigated how
      the lytic activity of LLO effects the context of presentation of two known LLO
      epitopes by either class I or class II MHC molecules. T cell hybridomas were used
      to monitor each peptide/MHC ligand. APCs infected with strains of Listeria
      expressing hemolytic LLO strongly presented the class I MHC epitope; however,
      this ligand was not well presented by cells infected with nonhemolytic Listeria.
      In contrast, there was almost no presentation of the class II-binding LLO epitope
      in cells infected with fully hemolytic Listeria. Only hemolysin-deficient
      Listeria were presented by class II MHC. Listeria expressing wild-type LLO but
      deficient in other virulence factors showed a presentation pattern equivalent to
      that of hemolytic Listeria. To address further the divergence of presentation, we
      used an intercellular spread assay to detect Ag presentation by cells neighboring
      the primarily infected one. We found that hemolytic Listeria were presented by
      both class I and II MHC on cells adjacent to the initially infected one(s).
      Finally, our kinetic analysis of presentation revealed that the class II ligand
      is presented over 4 h before the class I ligand. We have demonstrated that LLO's
      lytic activity potentiates presentation of listerial Ags by class I MHC and
      inhibits presentation via class II MHC. LLO-mediated intracellular localization
      (cytoplasmic vs endosomal) of bacteria corresponds to the operative presentation
      pathway.

PMID- 8757623
TI  - Genetic regulation of protective immune response in congenic strains of mice
      vaccinated with a subunit malaria vaccine.
AB  - The C-terminal 19-kDa, epidermal growth factor-like region of the merozoite
      surface protein 1 (MSP1) has been used as a vaccine to induce protective immunity
      to Plasmodium yoelii in mice and to Plasmodium falciparum in monkeys. To analyze
      the mechanisms and genetic regulation of this MSP1 vaccine-induced protection, we
      studied the immunologic correlates of protection in H-2 recombinant and congenic
      mouse strains on the B10 background. Multiple H-2-linked loci were found to
      contribute, each with a different mechanism. One locus mapped to the I-A region
      based on the strong protection in C57BL/10 mice compared with intermediate
      protection in B10.A(4R) mice and the lack of a difference between B10.AKM and
      B10.MBR mice. Differences in efficacy of passively transferred antisera from
      vaccinated C57BL/10 vs B10.A(4R) mice indicated that the protection regulated by
      the I-A locus was at least in part Ab dependent. Two loci mapped to the right of
      I-A (FE, H-2S, or H-2D) based on a correlation with the number of H-2k loci to
      the right of I-A in mice that were I-Ak. One effect was Ab independent and may
      correspond to a possible negative effect of the I-Ek locus. T cells from
      protected and nonprotected strains differed in their production of IFN-gamma and
      TNF-alpha following immunization with MSP1(19), but it was unclear how the
      differential patterns of cytokine expression related to the level of protection.
      Thus, MSP1(19) vaccine-induced protection is regulated by H-2-linked loci
      corresponding to two different immune mechanisms. These findings may indicate the
      need for more than one Ag in a vaccine to protect an HLA-diverse population.

PMID- 8757624
TI  - Soluble Fcgamma receptor type III (FcgammaRIII, CD16) triggers cell activation
      through interaction with complement receptors.
AB  - The type III-B Fcgamma receptor (FcgammaRIII-B) is a glycosyl
      phosphatidylinositol-linked receptor found on human neutrophils. A soluble form
      of FcgammaRIII-B (sCD16) corresponding to the extracellular region of the
      receptor circulates in plasma. In the present work, we have identified membrane
      receptors for sCD16. Soluble CD16 bound to CR3 (CDllb/CD18)- and CR4 (CDllc/CD18)
      positive leukocytes and cell lines, the labeling was inhibited by anti-CD11b,
      CD11c or CD18 mAbs, and the up-regulation of CR3 and CR4 led to an increased
      fixation of sCD16. Transfected eukaryotic cells expressing recombinant CD11b/CD18
      or CD11c/CD18 heterodimers but not those expressing CD11a/CD18 bound sCD16.
      Moreover, the lectin-like binding site of CR3 is probably involved in the
      interaction with sCD16, as suggested by inhibition studies using mAbs against CR3
      or sugars such as N-acetyl D-glucosamine, alpha- or beta-methyl D-glucoside,
      alpha- or beta-methyl D-mannoside, or zymosan. Thus, the complement receptors CR3
      and CR4 are membrane receptors for sCD16. Through this interaction, sCD16 induces
      a CR3-dependent production of IL-6 and IL-8 by monocytes. These results suggest
      that sCD16 plays a regulatory role in inflammatory processes and provide a
      molecular basis for the interaction between FcgammaRIII-B and CR3 described on
      the cell membrane.

PMID- 8757625
TI  - TNF-alpha bidirectionally modulates the viability of primitive murine
      hematopoietic progenitor cells in vitro.
AB  - It is well established that TNF-alpha can induce apoptosis in many normal and
      transformed cell types. The effects of TNF-alpha on cytokine-induced
      proliferation and differentiation of normal hematopoietic progenitors have been
      characterized extensively, whereas little is known about how TNF-alpha can affect
      their viability. The present studies suggest, based on experiments using delayed
      addition of growth-promoting cytokines as well direct viability assays, that TNF
      alpha bidirectionally affects the survival of individually cultured primitive Lin
      Sca-1+ hematopoietic progenitors, in that stem cell factor (SCF)-, granulocyte
      CSF-, IL-6-, and IL-11-induced survival is potently counteracted by TNF-alpha (42
      86%), whereas TNF-alpha synergistically enhances IL-1alpha-induced survival up to
      threefold. The bidirectional effects of TNF-alpha on hematopoietic growth factor
      induced survival of hematopoietic progenitors were reflected in that TNF-alpha
      enhanced apoptosis of Lin- Sca-1+ cells when combined with SCF, whereas TNF-alpha
      synergistically suppressed apoptosis in response to IL-1alpha.

PMID- 8757626
TI  - Complement activation by a B cell superantigen.
AB  - Staphylococcal protein A (SpA), acting as a B cell superantigen, binds to the Fab
      region of human VH3+ Igs. Using SpA abrogated of its IgG Fc binding activity (Mod
      SpA) as a model B cell superantigen, we determined whether such an interaction
      causes complement activation. Addition of Mod SpA to human serum led to
      complement consumption and the generation of C3a. To determine whether this
      complement activation 1) was due to an interaction between VH3+ Igs and the Fab
      binding site of SpA and 2) proceeded via the classical complement pathway, we
      tested a panel of monoclonal IgM proteins for the ability to hind C1q following
      interaction with SpA. C1q binding was restricted to SpA-reactive, VH3+ IgM
      proteins. To formally determine whether the binding of SpA to the reactive VH3+
      IgM proteins led to complement activation, we reconstituted the serum from a
      hypogammaglobulinemic patient with monoclonal IgM proteins and measured
      complement consumption and C3a generation following the addition of Mod SpA. We
      observed complement consumption and C3a production only in Mod SpA-treated serum
      reconstituted with a VH3+, SpA-binding, IgM protein. Taken together, these
      results provide compelling evidence that the interaction of the Fab binding site
      of SpA and VH3+ Igs can lead to complement activation via the classical pathway.
      This novel interaction may have significant implications for the in vivo
      properties of a B cell superantigen.

PMID- 8757627
TI  - The production of macrophage inflammatory protein-1 alpha by human basophils.
AB  - Macrophage inflammatory protein-1alpha (MIP-1alpha) has previously been shown to
      be produced by mononuclear cells, eosinophils, and neutrophils. Its production by
      basophils has not been investigated. The objective of this study was to
      investigate the production of MIP-1alpha by basophils. Peripheral blood basophils
      were separated by Percoll gradient centrifugation, cultured overnight, and
      processed for double immunocytochemistry using Abs against MIP-1alpha and
      FcepsilonRIalpha (alpha subunit of IgE receptor type 1). We demonstrated that
      basophils expressed immunoreactive MIP-1alpha upon stimulation with anti-IgE.
      Less than 5% of the basophils stained for MIP-1alpha without stimulation. The
      secretion of MIP-1alpha by basophils was studied by ELISA. In these experiments,
      basophils were further enriched to 65 to 99% (median, 86%) by a negative
      selection method. Basophils released MIP-1alpha when stimulated by Abs against
      IgE and FCepsilonRIalpha as well as IL-3 and the calcium ionophore, A23187. In
      parallel experiments, PBMC, eosinophils, and neutrophils did not produce MIP
      1alpha in response to anti-IgE, but they did so in response to A23187. No MIP
      1alpha release was detected in platelet preparations. Preincubation with IL-3 (15
      min or 18 h) augmented anti-IgE-included basophil MIP-1alpha production. The
      secretion of MIP-1alpha by basophils was detectable shortly after stimulation and
      gradually increased over 24 h. Since MIP-1alpha has potent inflammatory and
      histamine-releasing activities, its production by basophils may indicate a
      positive feedback mechanism for allergic inflammation.

PMID- 8757628
TI  - Beta-amyloid (25-35) peptide and IFN-gamma synergistically induce the production
      of the chemotactic cytokine MCP-1/JE in monocytes and microglial cells.
AB  - The molecular mechanisms involved in the development of senile plaques
      characteristic of aging and Alzheimer's disease are poorly understood. In this
      study, we examined whether human monocytes and murine microglial cells stimulated
      with the active fragment of amyloid beta-protein (Abeta(25-35)) express the
      monocyte chemotactic protein-1 (MCP-1)/JE. We show that upon incubation with
      Abeta(25-35), human monocytes accumulate MCP-1 mRNA and produce significant
      amounts of MCP-1. The effect of Abeta(25-35) on MCP-1 secretion was neither
      mimicked by a scrambled analogue nor affected by polymyxin B sulfate, even though
      the latter almost completely abolished the effect of LPS on MCP-1 expression.
      Murine microglial cells stimulated with Abeta(25-35) also expressed high levels
      of JE mRNA (the murine counterpart of MCP-1) and released bioactive chemotactic
      factors. In addition, we report that IFN-gamma significantly synergizes with
      Abeta(25-35) either in human monocytes or in murine microglial cells, and that
      Abeta(25-35) plus/minus IFN-gamma-mediated early induction of MCP-1 mRNA does not
      require new protein synthesis. Finally, we provide evidence that the Abeta(25-35)
      and Abeta plus IFN-gamma-induced production of MCP-1 is, in large part, mediated
      in an autocrine fashion by endogenous TNF-alpha. Taken together, our findings
      uncover another novel biologic action of Abeta(25-35) and might help in better
      understanding the mechanisms underlying mononuclear phagocyte recruitment and
      activation into amyloid deposits.

PMID- 8757629
TI  - Eosinophil granule proteins activate human heart mast cells.
AB  - Eosinophilia in humans is often associated with heart disease and cardiac
      localization of eosinophil granule proteins, and several results suggest that
      granule proteins mediate endomyocardial damage. Here we investigated the in vitro
      effects of the four principal eosinophil granule proteins (eosinophil cationic
      protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin, and
      eosinophil peroxidase (EPO)) on the activation of effector cells of inflammation
      (mast cells) isolated from human heart tissue (HHMC). ECP and, to a lesser
      extent, MBP (0.3-3 microM), but not eosinophil-derived neurotoxin and eosinophil
      peroxidase stimulated the release of preformed (histamine and tryptase) and the
      de novo synthesis of vasoactive and proinflammatory mediators (PGD2) from HHMC.
      Activation of HHMC by ECP and MBP was Ca2+- and temperature-dependent and was
      abolished by preincubation (15 min, 37 degrees C) with 2-deoxy-D-glucose (10 mM)
      and antimycin A (1 microM). There was a significant correlation between the
      maximal percentage of histamine release induced by ECP and anti-IgE from HHMC (rs
      = 0.73; p < 0.005), by MBP and anti-IgE (rs = 0.79; p < 0.001), and by ECP and
      MBP (rs = 0.65; p < 0.005). A positive correlation was also found between
      histamine and tryptase secretion (rs = 0.71; p < 0.001) and between histamine and
      PGD2 release induced by ECP from HHMC (rs = 0.85; p < 0.001). This is the first
      demonstration that some eosinophil cationic proteins, namely ECP and MBP, found
      at the site of heart damage in patients with eosinophilia, act as complete
      secretagogues on HHMC. This observation indicates another mechanism by which
      infiltrating eosinophils and their metabolic products cause inflammatory
      reactions and thus endomyocardial lesions in patients with eosinophilia.

PMID- 8757630
TI  - Rapid dephosphorylation of the GTPase dynamin after FcepsilonRI aggregation in a
      rat mast cell line.
AB  - As part of our studies aimed at exploring the potential role(s) of protein
      phosphatases in mast cell signaling, we analyzed the phosphorylation status of
      tyrosine-containing proteins in a rat mast (RBL) cell line that expresses both
      native rat high affinity IgE receptors (FcepsilonRI) and functional human
      FcepsilonRIalpha. After FcepsilonRI aggregation, there was a rapid increase in
      the tyrosine phosphorylation of a number of proteins, including those of m.w. 72
      and 110 kDa. Concurrent with these events, however, there was a rapid
      dephosphorylation of a 100-kDa protein that was constitutively phosphorylated in
      the unstimulated cells. Using a specific mAb, this 100-kDa protein was identified
      as the GTPase dynamin. Dynamin was shown to associate with the SH3 domain of the
      src-related tyrosine kinase p56lyn in RBL 2H3 cells both in vitro and in vivo.
      FcepsilonRI aggregation causes rapid internalization of the aggregated receptors
      via clathrin-coated pits and dynamin is known to play a role in clathrin-mediated
      endocytosis, so the dephosphorylation of dynamin may provide the signal for
      targeting the aggregated receptors to the endocytic pathway.

PMID- 8757631
TI  - Inhibition of platelet endothelial cell adhesion molecule-1 synthesis and
      leukocyte transmigration in endothelial cells by the combined action of TNF-alpha
      and IFN-gamma.
AB  - Endothelial cell (EC) junctions regulate circulating leukocyte extravasation and
      infiltration at inflammatory sites. Several lines of evidence show that platelet
      endothelial cell adhesion molecule-1 (PECAM-1), a specific component of EC
      junctions, is required for leukocyte transmigration through EC monolayers. In
      this paper, we examined the effects of two inflammatory cytokines, TNF-alpha and
      IFN-gamma, on PECAM-1 and vascular endothelial-cadherin/catenin organization. We
      found that the addition of inflammatory cytokines (TNF-alpha plus IFN-gamma in
      combination, for > or = 24 h) caused PECAM-1 to disappear from EC intercellular
      contacts. Confocal microscopy indicated that after treatment with the cytokines,
      PECAM-1 was rapidly internalized. In addition, a strong inhibition of PECAM-1
      synthesis and a decrease in PECAM-1 mRNA were observed. This phenomenon was only
      found when TNF-alpha plus IFN-gamma were used in combination. Adhesion of
      polymorphonuclear cells to doubly treated EC was increased compared with control
      cells or cells incubated with TNF-alpha or IFN-gamma separately. This was
      correlated with an increased expression of intercellular adhesion molecule-1.
      However, the disappearance of PECAM-1 from cell junctions after treatment with
      TNF-alpha plus IFN-gamma was accompanied by a marked reduction of leukocyte
      migration through EC monolayers. The correlation between PECAM-1 level and
      leukocyte transmigration was supported by transmigration inhibition assays using
      blocking anti-PECAM-1 mAb. These data indicate that PECAM-1 is a specific target
      of inflammatory cytokines and suggest that changes in its synthesis and
      organization might negatively modulate leukocyte recruitment.

PMID- 8757632
TI  - Substitution of two amino acids confers C3b binding to the C4b binding site of
      CR1 (CD35). Analysis based on ligand binding by chimpanzee erythrocyte complement
      receptor.
AB  - The chimpanzee (Ch) E complement receptor type 1 (CR177) appears to be an
      alternatively spliced product of the Ch CR1 gene transcript. Its cDNA-derived
      amino acid sequence contains complement protein-repeating modules (CP) 1-6, 28,
      29, and 30 in tandem and is 98.8% homologous to the corresponding regions of
      human (Hu) CR1. It differs from the C4b binding site of Hu CR1 only by two amino
      acids, Tyr for Ser37 in CP 1 and Asp for Gly79 in CP 2. However, in addition to
      binding C4b, Ch E binds C3b. As homologous substitution of one of these amino
      acids (Tyr for Ser37) was previously shown to not confer C3b binding, we reasoned
      that either single substitution of the other amino acid or a combination of the
      two amino acid changes would be required for C3b binding. To test this, using a
      truncated form of Hu CR1 that has a binding site only for C4b, we made these
      additional constructs. Single substitution of either amino acid did not affect
      the ligand binding or cofactor activity. However, the double substitution induced
      C3b binding and increased cofactor activity for C3b without changing the C4b
      binding property. Of interest, these two amino acids are also found in the
      homologous positions of CP 9 and 16, which form part of the C3b binding site of
      Hu CR1. Thus, Ch E CR177, one-third of the size and with only a single ligand
      binding site, by acquiring key amino acid substitutions, binds C3b and C4b and
      functions analogous to Hu E CR1.

PMID- 8757633
TI  - Donor-specific blood transfusion-induced tolerance in adult rats with a dominant
      TCR-Vbeta rearrangement in heart allografts.
AB  - Following allotransplantation, determinants encoded within the donor MHC are
      recognized by recipient T lymphocytes through their Ag receptor. In this study,
      we investigated the TCR Vbeta chain diversity of T cells infiltrating rejected
      and tolerated heart allografts in a model of donor-specific blood transfusion
      induced tolerance in MHC-mismatched congeneic rats. The PCR-based method that we
      used allows the diversity of Vbeta chains at the complementarity-determining
      region 3 level to be analyzed quantitatively. Our results show that the Vbeta
      repertoire usage in graft-infiltrating T cells was characteristic and different
      in tolerated compared with rejected grafts, and differed in both cases from the
      normal distribution of the Vbeta repertoire. An expansion of lymphocytes showing
      a conserved Vbeta18-Dbetal-Jbeta2.7 gene rearrangement was found, from the first
      day after grafting onward, in graft-infiltrating cells from all tolerant animals.
      This clone accounted for as much as 5% of the whole Vbeta repertoire in tolerated
      hearts, as evidenced by RNase protection assay. In contrast, we demonstrated
      that, of lymphocytes infiltrating rejected grafts, those with a Vbeta18 chain
      were diverse, and that even though by day 5 the conserved Vbeta18-Dbeta1-Jbeta2.7
      rearrangement was detectable, lymphocytes harboring this rearrangement
      represented less than 0.6% of the whole TCR-alphabeta+ T cell repertoire.
      Kinetics analysis revealed that the expansion of lymphocytes bearing this
      conserved rearrangement was elicited specifically by donor blood transfusion.
      Indeed, Vbeta18-Dbeta1-Jbeta2.7 transcripts were detected in PBL from transfused
      animals as early as 7 days after donor-specific blood transfusion. Finally, we
      provided evidence that this T cell clone belongs to the CD8+ subset. The putative
      role in inducing and maintaining the allograft tolerance of the CD8+ T cell clone
      harboring this public Vbeta18-Dbeta1-Jbeta2.7 rearrangement is discussed.

PMID- 8757634
TI  - Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory
      bowel disease. Crohn's disease LP cells manifest increased secretion of IFN
      gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5.
AB  - In this study, we investigate whether human inflammatory bowel disease (IBD)
      (ulcerative colitis and Crohn's disease) is associated with altered lymphokine
      secretion profiles, as recently found in various animal models of chronic
      intestinal inflammation. In initial studies, we determined the proliferative
      responses of purified lamina propria (LP) CD4+ T cells from patients with IBD
      under defined conditions of T cell stimulation. We found that IBD LP CD4+ T cells
      in comparison with control LP CD4+ T cells have diminished TCR/CD3 pathway
      proliferative responses, whereas CD2/CD28 accessory pathway proliferative
      responses are relatively preserved. In further studies centering on lymphokine
      production, we showed that LP T cells from inflamed Crohn's disease mucosa
      manifest increased IFN-gamma secretion compared with control LP T cells,
      particularly when stimulated via the CD2/CD28 pathway. Subsequent ELISPOT
      analysis indicated that this was due to an increased number of IFN-gamma
      secreting CD4+ T cells. In contrast, IL-4 and IL-5 production by Crohn's disease
      LP T cells was decreased compared with that of control LP T cells. Of interest,
      IL-2 production by Crohn's disease LP T cells was also reduced, as was IL-2
      production by peripheral blood T cells. In parallel studies, LP T cells from
      inflamed ulcerative colitis mucosa stimulated via either the TCR/CD3/CD28 or
      CD2/CD28 produced increased amounts of IL-5, again when measured either as
      secreted IL-5 or by ELISPOT analysis. Such increased IL-5 production was not
      associated with increased IL-4 secretion and, in contrast to Crohn's disease,
      ulcerative colitis LP T cell production of IL-2 and IFN-gamma was normal. Taken
      together, these studies provide strong evidence that the immunopathologic process
      characteristic of the two major forms of IBD is associated with very different
      cytokine secretion patterns. These different patterns may determine the type of
      inflammatory process present.

PMID- 8757635
TI  - Effect of Mycobacterium tuberculosis on HIV replication. Role of immune
      activation.
AB  - The prevalence of Mycobacterium tuberculosis (MTB) has increased worldwide, in
      part due to the HIV epidemic. Epidemiology data have demonstrated that HIV
      infected individuals are more susceptible to MTB disease, which may lead to an
      acceleration in the progression of HIV disease. The purpose of this study was to
      determine whether MTB modulates HIV infection in vivo and to delineate the
      mechanisms involved by using in vitro model systems. Plasma viral load was
      measured in HIV-infected individuals before, during, and after the development of
      MTB disease; a 5- to 160-fold increase in viral replication was observed during
      the acute phase of MTB disease. In order to evaluate the mechanisms involved in
      this MTB-induced HIV replication, we used an in vitro system of primary PBMC and
      lymph node mononuclear cells isolated from HIV-infected individuals. The data
      demonstrated that MTB induced HIV replication in CD8+ T cell-depleted lymphocytes
      from HIV-infected individuals with a history of purified protein derivative (PPD)
      positivity but not in those who were PPD negative; this induction of HIV
      replication correlated with the level of cellular activation. In an in vitro
      acute HIV infection model, MTB increased HIV replication in PBMC from healthy
      donors with a history of PPD positivity, but not in PBMC from PPD-negative donors
      and this induction of viral replication also correlated with cellular activation.
      In conclusion, MTB increased HIV replication in vivo and in an in vitro model.
      This MTB-mediated viral production likely occurs through Ag-specific activation
      and infection of responding T cells.

PMID- 8757636
TI  - Quantitative thresholds of MHC class II I-E expressed on hemopoietically derived
      antigen-presenting cells in transgenic NOD/Lt mice determine level of diabetes
      resistance and indicate mechanism of protection.
AB  - Two homozygous lines of transgenic NOD/Lt mice expressing MHC class II I-E
      molecules at quantitatively different levels were utilized to study mechanisms of
      I-E-mediated diabetes prevention. In line 12, I-E expression on APC at levels
      comparable with that in BALB/cByJ controls conferred only partial diabetes
      resistance. In line 5, greater than normal I-E levels on APC correlated with
      nearly complete resistance. Levels of endogenously encoded I-Ag7 correlated
      inversely with transgene-induced I-E expression. T cell transfer experiments into
      NOD/severe combined immunodeficient mice demonstrated the presence of pathogenic
      T cells in I-E+ donors, and that continuous expression of I-E on hemopoietically
      derived APC was required to block their pathogenic function. T cells from
      transgenic and nontransgenic NOD/Lt mice primed in vivo against the beta cell
      autoantigen 65-kDa isoform of glutamic acid decarboxylase (GAD65) and two
      peptides derived from this protein proliferated when restimulated in vitro.
      However, reverse-transcription PCR and ELISA measurements of cytokine mRNA and
      protein levels showed that the GAD65-reactive T cells from both line 5 and line
      12 mice produced higher levels of IL-4 and lower levels of IFN-gamma than similar
      T cells from standard NOD/Lt mice. Thus, the inverse relationship between I-E and
      I-Ag7 expression was associated with qualitative differences in T cell responses
      to putative beta cell autoantigens. Collectively, these data indicate
      quantitative increases in I-E expression on APC may block insulin-dependent
      diabetes mellitus by altering the balance of cytokines produced by beta cell
      autoreactive T cells.

PMID- 8757637
TI  - Costimulatory effects of T cell proliferation during infection with human T
      lymphotropic virus types I and II are mediated through CD80 and CD86 ligands.
AB  - The modulation of expression of CD80 and CD86 on T cells following infection with
      human T lymphotropic virus (HTLV)-I/II and its functional importance in T-T cell
      interactions was examined. Infection with HTLV-I/II leads to constitutive
      expression of CD80 and CD86, concomitant to down-modulation of CD28 on T cells.
      The CD80/CD86+ HTLV-infected T cells stimulated proliferation of allogeneic and
      autologous resting T cells, which could be specifically blocked by a soluble CTLA
      4Ig chimeric protein, anti-CD80 or anti-CD86, but not by anti-CD54. It was
      necessary to inhibit interaction with both ligands (CD80 and CD86) to optimally
      block HTLV-mediated proliferation of allogeneic and autologous resting T cells.
      Simultaneous addition of anti-CD8O and anti-CD86 Abs also inhibited production of
      IFN-gamma, TNF-alpha, and IL-4, with no effect on IL-10 production, for both allo
      and autologous T cell proliferation. Further, there was a direct correlation
      between the spontaneous proliferation of lymphocytes from patients infected with
      HTLV-II and expression of CD80, which could be blocked by simultaneous addition
      of anti-CD80 and anti-CD86. Taken together, these results suggest that HTLV
      infected CD80/CD86+ T cells serve as APCs, leading to a sustained proliferation
      of T cells, and that both ligands participate in allostimulation, autologous
      proliferation, as well as spontaneous proliferation of HTLV-II-infected PBMC.

PMID- 8757638
TI  - Murine glomerulotropic monoclonal antibodies are highly oligoclonal and exhibit
      distinctive molecular features.
AB  - We recently produced a panel of seven glomerular-binding mAbs from a nephritic
      MRL-lpr mouse that bind to histones/nucleosomes (group I) or DNA (group II)
      adherent to glomerular basement membrane. To elucidate the molecular basis of
      their binding and ontogeny, we sequenced their variable (V) regions, analyzed the
      apparent somatic mutations, and predicted their three-dimensional structures.
      There were two clonally related sets (3 of 4 in group I, 3 of 3 in group II) both
      of the VHJ1558 family, and one mAb of the VH 7183 family. V region somatic
      mutations within clonally related sets had little effect on glomerular binding
      and did not appear to be selected for based on glomerular binding. The VH regions
      were most homologous with those from autoantibodies to histones, DNA, or IgG
      (i.e., rheumatoid factors), the Vkappa regions, with those from autoantibodies to
      small nuclear ribonucleoproteins (snRNP). The VH regions also exhibited an
      unusual VD junction (in the group I clonally related set) and an overall high
      content of charged amino acids (arginine, aspartic acid) in complementarity
      determining regions (CDRs), particularly in CDR3. Molecular modeling studies
      suggested that the Fv regions of these mAbs converge to form a flat, open surface
      with a net positive charge. The CDR arginines in group I mAbs; appear to be
      located in Ag contact regions of the binding cleft. In sum, these data suggest
      that glomerulotropic mAbs are a highly restricted set of Abs with distinctive
      molecular features that may mediate their binding to glomeruli.

PMID- 8757639
TI  - Autoimmune Sjogren's-like lesions in salivary glands of TGF-beta1-deficient mice
      are inhibited by adhesion-blocking peptides.
AB  - The targeted disruption of the TGF-beta1 gene in mice (TGF-beta1 -/-) leads to
      extensive inflammation in vital organs, cachexia, and death within 3 to 4 wk.
      Significant inflammatory lesions develop initially in the periductal regions of
      the salivary glands and escalate as the animals become symptomatic. These
      inflammatory sites, characterized by lymphocytic infiltration and increased
      proliferation, cytokine mRNA expression, and IgG-positive cells, resemble lesions
      of Sjogren's syndrome. Moreover, the inflammatory pathology, enhanced MHC
      expression, and Ab production are consistent with an autoimmune-like etiology.
      Glandular atrophy and loss of acini with reduced saliva production appear to
      contribute to the wasting syndrome characteristic of the TGF-beta1 -/- mice. To
      determine whether the structural and functional defects were developmental due to
      the absence of TGF-beta1 or secondary to the inflammation, TGF-beta1 -/- mice
      were treated with synthetic fibronectin peptides, which block leukocyte
      infiltration. Daily systemic injections of RGD, CS-1, and/or peptides derived
      from the heparin-binding region of the A chain not only prevented leukocyte
      infiltration in the salivary glands of the TGF-beta1 -/- mice, but also reversed
      the acinar and ductal derangements. These data suggested that salivary gland
      development is not jeopardized in the absence of TGF-beta1, but that the
      extensive infiltration of inflammatory cells compromises glandular structure and
      function. The essential nature of TGF-beta1 in controlling inflammatory and
      immune processes is confirmed by these studies. Moreover, these TGF-beta1 -/-
      mice provide an important model of autoimmune disease that can be used in the
      design of therapeutic interventions.

PMID- 8757641
TI  - Serious flaws concerning the display and interpretation of flow cytometric data.

PMID- 8757640
TI  - Altered cytokine production and accessory cell function after HIV-1 infection.
AB  - We investigated cytokine production and accessory cell function in human
      macrophage hybridoma cell lines and primary monocytes after infection with HIV-1.
      HIV-1 infection induced IL-10 production in the macrophage hybridoma cell line
      with loss of IL-12 1 wk after infection. There were also significant increases in
      production of IL-10 (537 +/- 521 vs 687 +/- 625 pg/ml) while there was a
      reduction in IL-12 (6.3 +/- 3.1 vs 1.2 +/- 1.0 pg/ml, p = 0.021) in the primary
      monocytes 5 days after HIV-1 infection. In addition, the hybridoma cell lines and
      primary monocytes failed to support PHA, Con A, PWM, or anti-CD3- induced T cell
      proliferation 1 wk after infection. The viability of the T cells cocultured with
      the HIV-1-infected macrophage cell lines or the primary monocytes as determined
      by propidium iodide staining was unaltered and there was no increase in apoptosis
      specific DNA strand breaks or increased expression of Bcl-2 in the T cells. No
      soluble suppressor factor was present, since UV-inactivated supernatants from the
      hybridoma cell line and primary monocytes failed to inhibit mitogen- and anti-CD3
      induced T cell proliferation. Early events in T cell activation, including
      calcium flux and phosphotyrosine kinase activity, were intact in the T cells
      cocultured with the HIV-1- infected hybridomas and monocytes but there was
      reduced IL-2 production. Addition of exogenous IL-2 restored the proliferative
      responses. Taken together, these data suggest that alteration of cytokine
      production and accessory cell function for mitogens and anti-CD3-induced T cell
      proliferation independent of induction of apoptosis, suppressor factor
      production, or inhibition of T cell signaling occurs very early after HIV-1
      infection and may contribute to the global immunosuppression observed in AIDS.

PMID- 8757642
TI  - Suspension of the hospital doctor.

PMID- 8757643
TI  - Reflections of a humble media man.

PMID- 8757644
TI  - The Herald of Free Enterprise--corporate manslaughter?

PMID- 8757645
TI  - Litigation and medical negligence: a plaintiff's view on the need for change.

PMID- 8757646
TI  - Earprints in identification.

PMID- 8757647
TI  - The incompetent doctor: the remedy. Medical (Professional Performance) Act 1995.

PMID- 8757648
TI  - Commentary: the changing world of radiography education.

PMID- 8757649
TI  - Commentary: renal nuclear medicine. Report on a joint meeting of the BIR's
      Nuclear Medicine Sub-Committee in association with the IPEMB Radionuclide Special
      Interest Group, held at the British Institute of Radiology, London, on 22
      February 1996.

PMID- 8757650
TI  - 3M Mayneord Memorial Lecture: functional brain imaging--an overview.
AB  - Several methods can detect or infer the disruption of basic brain physiology;
      these methods include the techniques of computerized axial tomography, magnetic
      resonance imaging, positron emission tomography, single photon emission computed
      tomography, electroencephalography, magnetoencephalography, and magnetic
      resonance spectroscopy. Until recently any information on the actual function of
      the brain has been restricted to that deduced from the clinical examination, as
      most imaging methods have been limited to providing only anatomical references.
      In the past 10 years magnetic resonance has become a standard part of many
      neuroradiological practices. Tremendous advances in computed tomography have
      resulted in dramatic improvement in both image resolution and imaging times.
      During the 1990s, as interest shifts toward the analysis of brain function or
      dysfunction, the focus on the brain's electrical activity has resurged.
      Functional evaluation techniques, such as magnetoencephalography, began in the
      1960s and early 1970s; sophistication in the technology has led to much shorter
      examination and analysis times, leading to further clinical utility.
      Magnetoencephalography, when combined with magnetic resonance images, forms a
      functional image of the brain, or magnetic source image. The advent of such
      methods for evaluating actual functional activity of the brain has resulted in
      new clinical applications for previous methods of brain imaging and the arrival
      of new clinical imaging modalities.

PMID- 8757651
TI  - Magnetic resonance imaging in macromelia and macrodactyly.
AB  - We report five cases presenting with soft tissue and bone overgrowth that
      demonstrate the ability of MRI to establish a diagnosis in the absence of
      specific clinical features. Disorders included macrodystrophia lipomatosa,
      angiolipomatosis, Klippel-Trenaunay-Weber syndrome, blue rubber bleb naevus
      syndrome and one case of segmental limited hypertrophy. The MRI appearances, and
      other radiological features of these conditions are discussed. MRI is recommended
      in all cases of macrodystrophy when the clinical features and plain film findings
      are indeterminate.

PMID- 8757652
TI  - Technetium-99m-HMPAO labelled leucocytes in the detection and monitoring of
      inflammatory bowel disease in children.
AB  - This study was a retrospective evaluation of the use of technetium-99m
      hexamethylpropyleneamineoxime (HMPAO) labelled leucocytes in the investigation of
      suspected inflammatory bowel disease in children. The images were analysed in 35
      children and the findings were compared with the results of endoscopy/biopsy,
      barium studies and antinuclear cytoplasm antibody (ANCA) serology. The
      sensitivity of the white cell scan was 83% and the specificity 81%. This compares
      well with other studies in adults and is superior to barium investigations. The
      technique is recommended as a first line investigation to detect inflammatory
      bowel disease with a resultant reduction in the use of endoscopy and barium
      imaging.

PMID- 8757653
TI  - Effects of microwave tissue coagulation on the livers of normal rabbits: a
      comparison of findings of image analysis and histopathological examination.
AB  - The livers of normal rabbits were subjected to microwave tissue coagulation
      (MTC), and comparison was made of the subsequent time-course changes in tissue
      observed on MRI, CT and histopathological examination. 16 rabbits were used. MTC
      was performed with a 21 gauge needle electrode inserted into the liver at
      laparotomy. 1-2 h after thermal coagulation, a region with slightly lower
      attenuation than that of surrounding normal liver parenchyma was observed on CT,
      and no enhancement was detected. With MRI, change from high signal intensity to
      iso-signal intensity from the inner zone to the margin was found on T1 weighted
      images (T1WI), and heterogeneous high signal intensity was observed on T2
      weighted images (T2WI). On Gd-DTPA enhanced MRI, no enhancement occurred. 1-4
      weeks after coagulation, the cellular structure at the site of coagulation was
      lost on histological examination, and the tissue became necrotic. On CT,
      homogeneous water density was observed, and no enhancement was detected. With
      MRI, regions of iso- or slightly low signal intensity were observed on T1WI, and
      regions of heterogeneous high to low signal intensity were seen on T2WI. After 1
      week, a granulation layer consisting mainly of fibrous tissue developed, and a
      ring-shaped enhancement was observed in the low signal intensity region on T1WI
      and in the high signal intensity region on T2WI. The ring-shaped enhancement was
      also noted on CT. MRI appears to be useful for observation of time-course changes
      following MTC therapy because of its sensitivity in the detection of tissue
      changes.

PMID- 8757654
TI  - Cross-calibration of a fan-beam X-ray densitometer with a pencil-beam system.
AB  - This study describes the cross-calibration of two Hologic bone densitometers, one
      using a fan-beam X-ray source (QDR4500/A) and the other a pencil-beam source
      (QDR1000/W). The QDR4500/A allows spine and hip measurements to be made at three
      principal speeds. Results from two spine phantoms and 154 patients showed no
      significant difference in the absolute values or precision between speeds. The
      middle speed (taking 1 min to scan an adult lumbar spine) was used for the
      comparison between the instruments. The two densitometers were compared using two
      spine phantoms and 182 patients. In vivo measurements were made of all lumbar
      spine, hip, forearm and whole body sites. Regression lines, constrained to pass
      through the origin, were calculated. Slopes for total bone mineral density (BMD)
      for each scan type ranged between 0.994 and 1.029, the best value being found for
      forearm (1.000). Scatter graphs of the individual points were generated and
      showed results slightly worse than would be expected from repeat measurements on
      a single machine (79-88% fell within the expected 2 SD range). A trend for the
      QDR4500/A to overestimate BMD at low values and underestimate it at high values
      was seen in the femoral neck. The trend was more significant in the lumbar spine.
      There was an overestimate of total hip BMD throughout the range. Slopes of the
      regression lines for area and bone mineral content (BMC) were used to improve
      cross-calibration between the systems on a site-to-site basis, after which the
      results improved to a level consistent with repeat measurements on a single
      machine (81-94% within 2 SD). At present only global, rather than site-specific,
      correction factors can be employed for the spine and hip and no overall
      improvement in cross-calibration was possible. We conclude that although global
      correction factors allow adequate cross-calibration to be achieved, improvements
      could be made by the use of scan-site-specific factors.

PMID- 8757655
TI  - A portable system for measuring bone mineral density in the pre-term neonatal
      forearm.
AB  - Current systems used to measure bone mineral content (BMC) in the neonate have
      the major drawback that the child must be well enough to be moved to the scanner.
      Consequently, low birth weight pre-term neonates, a group at particular risk of
      mineral compromise, cannot be measured. This paper describes a portable neonatal
      bone mineral device capable of measuring bone mineral in the incubator. It uses a
      radiation sensitive, charge coupled device (CCD) to acquire a bone mineral image
      enabling bone mineral to be measured at various sites. It measures bone mineral
      density (BMD) with a precision of 5.5 mg cm-2 in vivo, reduced to 7.5 mg cm-2
      when repositioning between scans is taken into account. The procedure takes under
      5 min with an image acquisition time of 30 s and an absorbed radiation dose to
      skin of 6 microSv. Calibration has been undertaken with aluminium foils of
      differing thickness to confirm the linearity of the system throughout the
      intended measurement range. A regression line fitted to the data demonstrated
      linearity and correlation between BMD and aluminium thickness with r = 0.99 (p <
      0.0001). Preliminary measurements on pre-term neonates show values of BMD ranging
      from 43 to 115 mg cm-2 in babies aged 23-41 weeks post-conception. These figures
      are within the linear range of the system.

PMID- 8757656
TI  - Occupational dose to the radiographer in dual X-ray absorptiometry: a comparison
      of pencil-beam and fan-beam systems.
AB  - The introduction of advanced dual X-ray absorptiometry (DXA) scanners with fan
      beam geometry, improved image definition and faster scan times raises the
      question as to whether there is a significant radiation dose to the radiographer.
      We have measured the radiation dose to the operator from studies performed on
      four DXA systems; the Lunar DPX, Hologic QDR-1000, QDR-2000 plus and QDR-4500.
      The results were compared with the radiographer dose from 99Tcm-MDP radionuclide
      bone scanning, where it is not usual to use a radiation barrier between the
      patient and the operator, and 18F-FDG positron emission tomography (PET) scanning
      where it is usual to protect staff. Ambient dose equivalent rate averaged over 1
      h at 1 m from the patient with the DXA systems working at maximum patient
      throughput were 0.012, 0.12, 2.1 and 2.4 microSv h-1, respectively, for the DPX,
      QDR-1000, QDR-2000plus and QDR-4500. Annual operator dose for the DPX and QDR
      1000 was well below the 1 mSv limit for members of the public recommended by the
      International Commission on Radiological Protection (ICRP) (1990). Results for
      the QDR-2000plus and QDR-4500 were similar to a radionuclide bone scan (2.2
      microSv h-1), but smaller than for a PET scan (8.9 microSv h-1), and were close
      to the 5 mSv year-1 limit for a supervised area defined in the 1985 Ionising
      Radiation Regulations. Precautions to reduce radiographer dose with fan beam DXA
      include placing the operator at least 2 m from the patient, scanning the right
      hip instead of the left and using scan modes with short scanning times.

PMID- 8757657
TI  - Radiation properties of a miniature X-ray device for radiosurgery.
AB  - An alternative technology for performing interstitial intracranial radiosurgery
      is presented. Treatments are performed intraoperatively using a stereotactically
      mounted, miniature X-ray device. A concentrated, spherical pattern of X-rays is
      generated about the tip of a needle-like probe, which is inserted into the site
      of the lesion allowing the absorbed dose to healthy tissue to be minimized. A
      description of the device is given and results of investigations into the
      operating characteristics discussed.

PMID- 8757658
TI  - Incidence and possible aetiological factors in the development of pelvic
      insufficiency fractures following radical radiotherapy.
AB  - Five patients out of a total of 183 treated with radical radiotherapy for
      carcinoma of cervix at The Royal Marsden Hospital from 1991 to 1994 inclusive
      have developed severe pelvic fractures. Two patients had rheumatoid arthritis,
      one of whom died as a result of the radiation induced damage. This patient
      developed radiological evidence of radionecrosis within 1 month of completing
      radiotherapy. There are very few reports in the literature of such a rapid onset.
      We suggest that the presence of a connective tissue disorder in a patient with
      other risk factors such as steroid use, old age and osteopenia should alert the
      clinician to the risk of radionecrosis following radical irradiation.

PMID- 8757659
TI  - Dose and image quality in mammography with an automatic beam quality system.
AB  - Radiation dose, contrast and image quality for automatic beam quality selection
      (OPDOSE) with the Siemens Mammomat 3000 has been investigated for different
      breast thicknesses and compared with those found using manually set tube
      potentials and a molybdenum target and filter. Automatic beam quality selection
      was found to have a negligible effect for breasts with a compressed breast
      thickness of less than 45 mm. However, for larger breasts substantial dose
      savings were achieved for a loss in contrast. For mammograms of compressed breast
      with a thickness in excess of 60 mm the mean glandular dose (MGD) per film was
      2.90 mGy for manually selected tube potentials with a molybdenum/molybdenum
      target filter combination as compared with 1.87 mGy using 26 kVp and a tungsten
      target with rhodium filtration. The contrast loss in using OPDOSE was measured
      with a test object to be about 10% for breast thicknesses in excess of 45 mm. The
      standard breast model, which assumes a 50% glandular content, did not provide a
      good fit to the MGD for women attending for breast screening in the age range 50
      to 64 years.

PMID- 8757660
TI  - Contrast reduction using energy dependent intensifying screens.
AB  - The speed of intensifying screens, in particular rare earth screens, increases
      with beam energy. Using such a screen, the measured contrast of an aluminium
      disc, with optical densities in the linear region of the characteristic curve,
      was found to be significantly and consistently less than that calculated from the
      gamma of the film-screen combination for all tube potentials from 40 to 140 kVp.
      This contrast reduction effect can be explained in terms of the filtering action
      of the disc which increases the effective energy of the beam. Hence, the film
      screen combination is exposed to X-rays which have different effective energies.
      This results in two characteristic curves of different speed. The contrast of the
      disc image is not dependent on the gamma of either curve, but an effective gamma
      which links the two curves. This effective gamma is less than the gamma of either
      curve. Contrast calculated using the effective gamma gave good agreement with the
      measured contrast of the disc image over the tube potential range examined.

PMID- 8757661
TI  - Short communication: renal function and the excretion of contrast agents.
AB  - The renal excretion of intravascular iodinated X-ray and gadolinium chelate MR
      contrast is examined theoretically. An expression is derived for the proportion
      of an administered dose of such an agent excreted in any given time in the face
      of varying levels of renal function. It is shown that a family of curves may be
      generated from which an estimate of this proportion for any time may be made.
      Some circumstances in which such knowledge may be useful are briefly discussed.

PMID- 8757662
TI  - Case report: bronchial to coronary artery anastomosis--a potential hazard in
      bronchial artery embolization.
AB  - Bronchial artery embolization is a well-established treatment for patients with
      haemoptysis. Communications between coronary and bronchial vessels have been seen
      on coronary angiography. This report describes a case of a bronchial to coronary
      artery anastomosis diagnosed prior to embolization in a patient with haemoptysis.

PMID- 8757663
TI  - Case report: Kaposi's sarcoma of the rectum--treatment with radiation therapy.
AB  - The number of patients afflicted with the acquired immune deficiency syndrome
      (AIDS) is on the rise. About 30% of AIDS patients develop Kaposi's sarcoma.
      Although the skin is the most common site of involvement, lesions may encompass
      the gastrointestinal tract. The purpose of this report is to describe a patient
      with AIDS related Kaposi's sarcoma of the rectum, successfully treated with
      radiation therapy. We believe this to be a useful technique in the treatment of
      this condition.

PMID- 8757664
TI  - Case of the month: a pulmonary embolus, or what?

PMID- 8757665
TI  - Correspondence. Quantitative perfusion parameters of focal nodular hyperplasia
      and normal liver parenchyma as determined by electron beam tomography.

PMID- 8757666
TI  - An audit of velopharyngeal incompetence treated by the Orticochea pharyngoplasty.
AB  - An audit of patients with velopharyngeal incompetence treated by the Orticochea
      pharyngoplasty was undertaken. 54 patients who had been treated by a single
      surgeon over a 10-year period were identified. All patients had pre- and
      postoperative speech therapy and were followed up for an average of 6 months.
      49/54 patients had lessening of their nasal escape; in 40/54 it was eliminated
      completely. Nasal resonance was assessed as normal in 46/54 of patients
      postoperatively. The results are compared with those of other similar studies.

PMID- 8757667
TI  - Effects of low dose intra-arterial monoclonal antibodies to ICAM-1 and CD11/CD18
      on local and systemic consequences of ischaemia-reperfusion injury in skeletal
      muscle.
AB  - The aim of this study was to investigate the effects of intra-arterial infusion
      of low doses of monoclonal antibodies (Mabs) against adhesion molecules (the
      neutrophil CD18 integrins, and the endothelial adhesion molecule, ICAM-1) on
      reperfusion injury in skeletal muscle. The rabbit rectus femoris muscle was
      rendered ischaemic for 2 1/2 hours. Mabs were infused (approximately 0.5 mg/kg)
      commencing 20 minutes before the end of ischaemia and for the first hour of
      reperfusion. 24 hours after reperfusion, the muscle was assessed for viability,
      oedema and neutrophil infiltration (myeloperoxidase (MPO) levels). The results of
      the viability assessment (control--20.9 (0-47.5)% [median (range)], anti-CD18-
      30.5 (3.0-89.4)%, anti-ICAM-1--27.9 (7.8-78.1)% and anti-CD18 combined with anti
      ICAM-1--45.2 (15.6-92.3)%) showed no significant differences between groups,
      while analysis of MPO in the postischaemic muscle showed that the anti-ICAM-1 Mab
      reduced neutrophil infiltration significantly. Furthermore, in contralateral
      unoperated muscles MPO levels were elevated 24 hours after ischaemia in the
      contralateral muscle. This increased neutrophil infiltration was prevented by
      pretreatment with anti-ICAM-1. These results suggest that low doses of anti-CD18
      and anti-ICAM-1 Mabs do not reduce reperfusion injury in skeletal muscle but may
      help to protect against systemic effects of severe trauma. The evidence suggests
      that reperfusion injury in this skeletal muscle model may be largely independent
      of neutrophil involvement.

PMID- 8757668
TI  - Sensory recovery following free TRAM flap breast reconstruction.
AB  - The free TRAM flap is now commonly used in breast reconstruction after
      mastectomy. A number of our patients reported anecdotally return of some
      sensation in their reconstructed breasts, despite being told beforehand that this
      was unlikely. This study measured return of sensation in a series of 21 patients,
      by studying both patients' subjective reporting of sensory return using a
      standardised questionnaire and objective evaluation of sensation with standard
      clinical tests. These included temperature and pain threshold and the use of the
      Semmes-Weinstein method. The study demonstrates that measurable sensory recovery
      occurred in 16 of our 21 patients (76%). 18 of the 21 patients (86%) reported a
      subjective feeling of sensation in the reconstructed breast and 7 (33%) claimed
      it felt the same as their normal contralateral breast. Sensory recovery usually
      commences about 6 months postoperatively and progressively improves over time.
      These findings demonstrate that the free tissue transfer method does not
      necessarily lead to an insensate reconstruction, as might be supposed.

PMID- 8757669
TI  - Secondary sternal repair following median sternotomy using interosseous
      absorbable sutures and pectoralis major myocutaneous advancement flaps.
AB  - A consecutive series of 19 patients were treated for median sternotomy dehiscence
      by secondary sternal closure with interosseous absorbable sutures and
      superimposed pectoralis major myocutaneous advancement flaps. These patients were
      selected for this treatment only on the basis of the quality and quantity of
      remaining bone stock after debridement. Using this technique there have been no
      failures of primary therapy with a zero 30-day mortality rate. All patients have
      achieved good functional and aesthetic results with mechanically stable sternums,
      wounds confined to the chest and elimination of sepsis. This technique has the
      advantages of being simple, safe and relatively quick and avoids many of the
      inherent complications and disadvantages of other techniques and flaps commonly
      used in the management of this complication.

PMID- 8757670
TI  - Reduction mammaplasty combined with pectoralis major muscle flaps for median
      sternotomy wound closure.
AB  - Sternal wound infection can be a problem in patients who undergo coronary artery
      bypass graft surgery and is usually treated with local flaps. Severe macromastia
      can cause a large wound dehiscence by inferolateral tension on the skin sutures.
      Chest wall reconstruction can be achieved by combining muscle flap coverage with
      reduction mammaplasty. Two musculoglandulocutaneous flaps can be designed, using
      two superiorly based pectoralis muscle flaps vascularising the medial portion of
      the glandular breast tissue. The flaps are advanced medially to the sternectomy
      site and the breast reduction is then completed by adjusting the lateral breast
      pillar to the medial breast pillar. A case in which this technique was
      successfully used is reported.

PMID- 8757671
TI  - A modified Bretteville technique for hypospadias.
AB  - A modified Bretteville technique for hypospadias repair is presented. This is a
      two-stage repair, utilising a preputial skin flap. The modification reduces the
      second stage to a day-case procedure. 40 cases are reported with good early
      functional and aesthetic results. The only major complications were two fistulae.
      There were no strictures.

PMID- 8757672
TI  - Endoscopic excision of large capsulated lipomas.
AB  - The technique of endoscopic excision of large capsulated lipomas is presented and
      the versatility of this method is discussed based on our clinical experience. We
      have applied this new technique in 6 cases. In all cases the lipoma was
      completely removed in one piece through a single incision, up to 1.5 cm in
      length. The endoscope made it possible to view the lipoma through a narrow space
      with a wide range of vision on a TV monitor. We stress that this method is not
      only appropriate as treatment for benign lipomas but also effective from a
      cosmetic point of view. The applications of the endoscope should widen in plastic
      surgery when the advantages of it are recognized and new operative approaches for
      using it are developed.

PMID- 8757673
TI  - The problem of bilateral foot reconstruction after severe burns.
AB  - Reconstruction of bilateral, distal lower limb defects presents a major
      reconstructive challenge. In the patient with a major burn injury, however, the
      problem of bilateral foot reconstruction is compounded by both the limited
      availability of normal unscarred donor sites and by the limited availability of
      recipient vessels. A case is presented where bilateral dorsum of foot defects in
      a patient with a 50% surface area burn were successfully reconstructed using a
      single parascapular free flap. The problems presented by this case are discussed.

PMID- 8757674
TI  - Cervical necrotising fasciitis with pharyngeal perforation: treatment and
      reconstruction.
AB  - We present a case of life-threatening necrotising fasciitis of the neck with
      acute pharyngeal perforation following a parapharyngeal abscess caused by
      tonsillitis. The joint occurrence of cervical necrotising fasciitis and acute
      pharyngeal perforation has not been previously reported. A new way of
      reconstructing the pharyngeal defect using an islanded submental perforator flap
      is presented.

PMID- 8757675
TI  - A combined flap technique for earlobe reconstruction in one stage.
AB  - Many of the techniques available for earlobe reconstruction require that the rest
      of the ear is in continuity with retroauricular skin and they usually need two
      stages; in some cases a graft is also required. We present a method to create an
      earlobe in one stage and without grafts, illustrated by one case report. The
      technique is a combination of the flap techniques of Davis and Zenteno Alanis,
      using an extended retroauricular flap together with an anterior ear flap.

PMID- 8757676
TI  - Iloprost and salvage of a free flap.
AB  - Despite the alluring pharmacological properties of prostacyclin and its stable
      analogue (iloprost), these substances are little used in plastic surgery. A case
      is presented in which iloprost resulted in persistent patency of the vessels
      supplying a free flap. A patient who had had failure of a free flap because of
      thrombosis distal to the arterial anastomosis had a second free flap. Thrombus
      formed distal to the arterial anastomosis of the second flap and recurred when
      the anastomosis was redone. The flap was perfused with urokinase and then
      iloprost. After this, iloprost was given intravenously peroperatively and for 12
      hours postoperatively. Postoperatively, the patient also received aspirin,
      ticlopidine and heparin. The flap survived without any late complications. A
      literature review offers confirmation of the advantages of using iloprost if
      microvascular anastomoses thrombose and during the reperfusion of flaps after
      prolonged ischaemia.

PMID- 8757677
TI  - Intravenous infusion of prostacyclin to prevent platelet thrombus during
      microvascular anastomoses.
AB  - Two cases are presented where the use of epoprostenol sodium (prostacyclin) was
      used intraoperatively to prevent platelet thrombus during arterial microvascular
      anastomoses. Both patients required a free muscle transfer at an unfavourable
      time following injury when platelet thrombus formation was a significant risk.

PMID- 8757678
TI  - Congenital bilateral zygomatico-mandibular fusion with mandibular hypoplasia.
AB  - We report a very rare case of congenital bilateral zygomatico-mandibular fusion
      with mandibular hypoplasia. Soon after birth, the patient underwent tracheotomy
      because of upper airway obstruction. At the age of one and a half years,
      reconstruction of the temporomandibular joint and lengthening of the ramus with a
      costochondral graft were performed. Only a few cases of congenital bony
      syngnathia revealed in this case have been described in the literature.

PMID- 8757679
TI  - Access to the axilla using Chinese finger traps.

PMID- 8757680
TI  - The seven flap-plasty.

PMID- 8757681
TI  - Paradoxical clinical consequences of peripheral nerve injury.

PMID- 8757682
TI  - Pseudotuberculoma silicoticum.

PMID- 8757683
TI  - Alzheimer's disease: genetics or environment?

PMID- 8757684
TI  - Isolation of influenzavirus A and B in PLC/PRF/5 cells.
AB  - Virus isolation was attempted in PLC/PRF/5 cells, a continuous primary liver
      carcinoma line, and secondary rhesus monkey kidney (2 degrees RhMK) cells from 19
      clinical samples from which influenza A (n = 4) and B (n = 15) had been isolated
      previously. Virus growth was determined by haemadsorption and immunofluorescence.
      Influenza A was recovered in both cell types from all four samples tested.
      Influenza B was re-isolated in both cell types from eight specimens, in PLC/PRF/5
      only from two, and in 2 degrees RhMK only from one; no virus was recovered from
      the remaining four. Cultures of either virus were haemadsorption- and
      immunofluorescence-positive by six days post-inoculation. Cytopathic effect
      produced by the influenza A isolates in PLC/PRF/5 was minimal following initial
      inoculation of specimens, but increased on subsequent passage. Influenza B
      isolates produced a cytopathic effect in PLC/PRF/5 similar in extent and speed of
      development to that in 2 degrees RhMK. These results suggest that PLC/PRF/5 may
      be a suitable continuous cell line, and an alternative to monkey kidney cells,
      for the isolation and monitoring of antigenic variation of influenza viruses.

PMID- 8757685
TI  - Human cord blood-derived large myeloid cells: spontaneous shape change and
      chemotactic movement.
AB  - We have demonstrated two aspects of the movement of large myeloid cells derived
      from cord blood mononuclear cells after culture in RPMI 1640 and 10% fetal calf
      serum for eight days. At this time cells assume various shapes including round,
      oval, veiled, elongated and dendritic. Interestingly, these shapes were not
      static. Time-lapse recording demonstrated that individual cells change shape
      quite dramatically over four hours. Some of the veils showed a great deal of
      activity, some elongated cells shrank into rounded forms, and rounded cells
      stretched out into dendritic cells or elongated forms. We have previously shown
      that the number of N-formyl-methionine-leucyl-phenylalanine receptors on the cell
      surface increase with culture time up to eight days. Furthermore, a rise in Ca2+
      was observed in response to 1 mumol/L N-formyl-methionine-leucyl- phenylalanine
      (chemotactic peptide) at the single cell level. In this paper we show the
      motility of cord blood-derived myeloid cells towards a chemotactic peptide
      concentration gradient leaking from a micropipette.

PMID- 8757686
TI  - Inter-observer variation of p53 immunohistochemistry--an assessment of a
      practical problem and comparison with other studies.
AB  - The aims of this study were to analyse the expression of p53 by
      immunohistochemistry in a range of malignant and pre-malignant conditions and to
      assess the degree of inter-observer variability in interpretation of p53
      immunostaining. Formalin-fixed paraffin-embedded sections from 28 colorectal
      carcinomas (CRC), 40 cervical intraepithelial neoplasia lesions (CIN), 22
      transitional cell carcinomas of the bladder (TCC), 10 invasive squamous
      carcinomas of uterine cervix and 21 squamous cell carcinomas of skin were
      examined. A polyclonal antibody was used in 90 cases. A monoclonal antibody was
      used in the remainder. Ten cases were stained with both. Aberrant expression of
      p53 protein was documented in 48% of squamous cell carcinomas of skin, 29% of
      CRC, 22% of CIN and 23% of TCC. All cases of squamous cell carcinoma of uterine
      cervix were negative. Inter-observer variation occurred in 7% of cases examined.
      This was confined to two tumour groups, TCC and CIN. Our results showed that p53
      oncoprotein expression by immunohistochemistry was identified in 26% of cases but
      the range was wide (0-48%) and appeared to be tumour specific. Inter-observer
      variability in the interpretation of immunohistochemical staining was low (7%)
      and was restricted to two tumour groups.

PMID- 8757687
TI  - Mineral changes in a transgenic mouse model for osteogenesis imperfecta.
AB  - A line of transgenic mice has been investigated that expressed moderate levels of
      an internally deleted human gene for the pro alpha 1(I) chain of type I
      procollagen to determine if they would make a good model for osteogenesis
      imperfecta (brittle bone disease). Previous workers have reported extensive
      fracturing in these mice, with femurs that were shorter and bone that had
      decreased ash weight, mineral and collagen content. These workers demonstrated
      increased brittleness in the bone by biomechanical measurements. The molar
      calcium to phosphorus ratio in bone from patients with osteogenesis imperfecta
      has previously been reported to be lower than that in normal human bone. Mineral
      changes were observed at the ultrastructural level in these mice and were
      comparable with those seen in patients with osteogenesis imperfecta. Bone from
      both transgenic and normal littermate mice was examined to determine if any
      similarity with the data for human osteogenesis imperfecta could be drawn. X-ray
      microanalysis of bone mineral demonstrated a lower calcium to phosphorus molar
      ratio in transgenic mouse bone than in normal littermates. Fourier-transform
      infra-red spectroscopy confirmed that the mineral present was apatitic in nature
      despite the lower calcium to phosphorus molar ratio. Multiple fracture calluses
      were present on the ribs and on the long bones of the transgenic mice; this was
      absent in normal littermates. This mouse model may lead to a better understanding
      of the underlying pathology resulting in fragile bones in osteogenesis
      imperfecta.

PMID- 8757688
TI  - Inter-relationships between glutamine and other biochemical and immunological
      changes after major vascular surgery.
AB  - It has been suggested that increased susceptibility to infection sometimes seen
      following surgery might be related to levels of circulating glutamine. However,
      previous studies have not investigated the degree of immune cell activation in
      relation to availability of glutamine after surgery. In seven patients plasma
      glutamine concentration decreased by about 50% immediately after major vascular
      surgery, and took 5 days to recover to normal levels. Although plasma glutamate
      concentration was inversely related to glutamine, glutamate levels were some
      three times lower. The circulating numbers of platelets, neutrophils, monocytes
      and lymphocytes (specifically CD4+ cells) were significantly related to both the
      concentration of glutamine and glutamate irrespective of time. However, there was
      no evidence of cell activation as indicated by expression of activation markers
      (CD69, CD25, CD71 or HLA-DR) on lymphocytes. Creatine kinase activity
      significantly increased after operation, indicating the presence of substantial
      post-operative trauma. Transferrin, iron and magnesium were the other biochemical
      parameters which significantly decreased after surgery, while albumin levels
      suggested that blood transfusions may have contributed to the changes seen.

PMID- 8757689
TI  - Amphotericin B: an update.
AB  - Amphotericin B is the most important clinically and best defined chemically of
      the macrolide heptaene antibiotics. A fermentation product of the soil
      actinomycetes Streptomyces nodosus, amphotericin B binds selectively to
      ergosterol in the cell membrane of susceptible fungi, inducing changes in
      permeability that can produce lethal cell injury. Available since 1960,
      amphotericin B remains the treatment of choice for most serious systemic fungal
      infections. This review highlights some important aspects of the physicochemical
      properties of amphotericin B and their utilisation in its quantitative
      determination in biological fluids. Its mechanism of action is re-appraised in
      the light of recent results with regard to its effects on the physical and
      functional properties of synthetic and natural membranes. Attempts to reduce its
      toxic effects to host cells and to improve its therapeutic index are evaluated.
      In addition, the therapeutic values of amphotericin B, apart from its antibiotic
      activity, are discussed.

PMID- 8757690
TI  - Iatrogenic epidemics of puerperal fever in the 18th and 19th centuries.
AB  - The epidemics of puerperal fever in the 18th and 19th centuries began soon after
      the creation of Lying-in hospitals in the mid-18th century. The primary purpose
      of these hospitals was to provide physicians with training in obstetrics in
      general and in forceps deliveries in particular. The first reports describing
      epidemics of puerperal fever, its contagiousness and control were made by British
      physicians in the latter half of the 18th century. Alexander Gordon provided
      epidemiological evidence of contagion in 1792, and Oliver Wendell Holmes in the
      USA reviewed these reports in his paper on outbreaks of puerperal fever around
      Boston in 1843. Ignaz Semmelweis in Vienna, unaware of previous work on this
      disease, re-discovered the actions required to control the contagion in 1847, but
      published his paper much later in 1861. A few enlightened doctors struggled to
      prove that puerperal fever was contagious and could be spread by doctors and
      midwives. Their peers and colleagues predominantly displayed apathy and ignorance
      until forced to act by the weight of evidence. However, it was the multitude of
      parturient women who paid the ultimate price for these iatrogenic epidemics.

PMID- 8757691
TI  - Cystic fibrosis and the pseudomonads.
AB  - The microbiology of pulmonary disease in cystic fibrosis has altered over the
      past 10 years. The major pathogens in this disease are now Pseudomonas aeruginosa
      and, increasingly, Pseudomonas cepacia. P. aeruginosa respiratory infection in
      these patients is rarely eradicated and this is often the only pathogen found at
      post-mortem. The most important points in the pathogenesis of this infection are
      probably the protective role of the bacterial mucoid exopolysaccharide and the
      interaction of various other bacterial factors with the immune system of the
      body. P. cepacia has recently emerged as the common isolate from the lungs of
      cystic fibrosis patients. The actual role of this organism in the progression of
      lung disease is poorly understood. There has been some speculation about the role
      of cross-infection in the acquisition of both of these organisms. The treatment
      of these infections is problematical because of the altered antimicrobial
      pharmaco-kinetics within the cystic fibrotic lung and the resistant properties of
      the organisms involved. Approaches which have been suggested recently include
      immunological interventions and genetic therapy.

PMID- 8757692
TI  - Acanthamoeba: ecology, pathogenicity and laboratory detection.
AB  - Acanthamoeba spp. are ubiquitous free-living protozoa found in a wide range of
      environmental niches. They are resistant to disinfectants, temperature variation
      and desiccation and are responsible for two recognised diseases in humans,
      granulomatous amoebic encephalitis and keratitis. Both infections are rare,
      although the latter is currently receiving more attention following the
      association between Acanthamoeba and the wearing of contact lenses. Laboratory
      diagnosis is unusual but not beyond the bounds of most routine clinical
      microbiology departments. In this review the various aspects surrounding the
      ecology, pathogenicity and laboratory detection of Acanthamoeba spp. are
      considered.

PMID- 8757693
TI  - Cervical intraepithelial neoplasia: false negative smears.
AB  - In the early days of cervical cytology there was a general assumption that
      mistakes would be a rare occurrence. These expectations were unrealistic given
      the fatiguing nature of the work and its dependence on human judgement. Media
      attention and the introduction of quality control have highlighted inadequacies
      in the service. The reasons for both sampling and screening errors which give
      rise to the issuing of false negative smear results need to be understood before
      measures can be taken to minimise them. An acceptable error rate should be
      recognised and, if possible, improved upon. Further investigations into the role
      of human papilloma virus (HPV) in the development of cervical cancer, and
      evaluation of automated screening, should lead to improvements in the cervical
      screening programme.

PMID- 8757694
TI  - Breast cancer: the search for new prognostic markers.
AB  - Node-negative breast cancer has become a major public health problem due to an
      increase in detection rates, and therefore clinical research in this field is
      expanding. In order to supply the correct therapy to an individual patient, the
      need for additional prognostic and predictive factors has led to identification
      of a plethora of potentially useful markers. However, no single prognostic marker
      currently available can give unequivocal information on prognosis and subsequent
      therapy.

PMID- 8757695
TI  - Lymphomatoid papulosis: a low-grade T-cell lymphoma?
AB  - Lymphomatoid papulosis is a chronic cutaneous lymphoid disease characterised
      clinically by the presence of recurrent papulonodular or plaque like lesions,
      which appear benign. Paradoxically, histological and cytopathological features
      demonstrate features of malignancy. This annotation highlight the current
      theories and technical advances into the assessment of this condition, with
      emphasis on possible pathogenic disease mechanisms.

PMID- 8757696
TI  - The immunoalkaline phosphatase technique in immunohistochemistry: the effect of
      permanganate-oxalate melanin bleaching upon four final reaction products.
AB  - Melanin bleaching prior to the application of primary antibody can alter the
      immunoreactivity of a number of antigens. The effect of melanin bleaching
      subsequent to antigen visualisation by four different chromogens used with an
      immunoalkaline phosphatase technique was investigated. Vector black was the only
      final reaction product that withstood exposure to the permanganate-oxalate
      sequence for a time sufficient to bleach melanin.

PMID- 8757698
TI  - Thoughts about food.

PMID- 8757697
TI  - Increase of blood donations found positive in the direct antiglobulin test
      detected by column methods--do we need to know?

PMID- 8757699
TI  - General practice: at yet another cross-roads?
AB  - There have been enormous changes in general practice over the past couple of
      decades but we are now in danger of seriously overloading the system with
      continuous change. Public health practitioners have a role in recognising the
      contribution of personal and primary care to the delivery of health care and
      should work with general practice to ensure a creative partnership.

PMID- 8757700
TI  - What is old age?
AB  - Use of the term "old age' in notifying deaths of residents in Oxfordshire nursing
      homes between 1984 and 1994 was matched with recorded age. 2264 records covering
      44 registered nursing homes were looked at. The oldest person referred to as
      dying from old age was 106, the youngest 69 years. The most general starting
      point for a diagnosis of old age was 77 though the years from the mid-eighties
      through the early nineties were taken by the majority of notifiers as fitting
      this description.

PMID- 8757701
TI  - Neurodevelopmental outcome at age two years amongst very low birth weight
      infants: results from a district general hospital.
AB  - STUDY OBJECTIVES: To describe the survival and neurodevelopmental outcome at age
      2 years of very low birth weight infants from routinely collected information in
      a district general hospital setting. DESIGN: Case note review and child health
      surveillance information was collected on all liveborn < 1,501 g infants born in
      our district general hospital over 4 years, 1989-1992. Main outcome measures were
      (a) death before discharge, (b) normal neurodevelopment at age 2 years, (c) minor
      impairment at age 2 years, (d) major impairment at age 2 years. Comparability
      with other published work was examined. SETTING: Rotherham District General
      Hospital, a maternity unit with neonatal intensive care facilities. Selected
      infants were transferred for continuing neonatal intensive care to a tertiary
      unit. Most infants were followed up to age 2 years in a dedicated clinic.
      SUBJECTS: Liveborn very low birth weight infants. MAIN RESULTS: Over the 4 year
      period there were 125 liveborn infants < 1,501 g; 93 (74%) survived to discharge
      home. Defined neurodevelopmental outcome measures were easily retrievable in 92
      children at age 2 years from hospital case notes or child health surveillance
      records. Sixty-four children (70%) were neurodevelopmentally normal, 10 children
      (11%) had a major impairment (mostly cerebral palsy) and 18 (19%) had an isolated
      minor impairment. CONCLUSIONS: The incidence of major impairment amongst very low
      birth weight infants in our district general unit is broadly comparable with
      other published series. Outcome measures of neurodevelopmental status are
      available from routinely collected clinical information. The use of such measures
      to make detailed comparisons between units is problematical because of a wide
      range of confounding variables.

PMID- 8757702
TI  - A one-year community study of under-fives in rural Ethiopia: health and
      behavioural determinants of morbidity.
AB  - Based on a one-year weekly home surveillance study, morbidity patterns of 1,304
      children under five years of age in a rural Ethiopian community were measured,
      together with nutritional and health behavioural determinants. Using Poisson
      regression models, the study showed that nutritional and health care factors make
      a significant impact on under-five morbidity. Gastroenteritis was particularly
      associated with child care factors, while acute respiratory infections were
      particularly associated with nutritional factors. Lack of immunization, low
      birthweight and pre-term delivery (more than one month early) were not found to
      have any independent effect on morbidity. Breast feeding was universal, but the
      introduction of supplementary foods was found to protect from excess morbidity.
      The study concludes by discussing possible applications of the results in
      intervention programmes.

PMID- 8757703
TI  - Urinary schistosomiasis: options for control within endemic rural communities: a
      case study in south-west Nigeria.
AB  - A preliminary investigation was conducted into factors that may bring about
      control of morbidity due to endemic urinary schistosomiasis in rural communities.
      A Knowledge, Attitudes, Practices and Beliefs (KAPB) study was conducted among
      primary schoolchildren (those with more than four years elementary education) in
      Ogbagba village, Osun State, Nigeria, from October 1990 to December 1993, to
      ascertain their understanding of urinary schistosomiasis. The study further
      assessed the potential of subjective haematuria, i.e. asking children with
      haematuria in the recent past to so indicate, in detecting urinary
      schistosomiasis. It was established that subjective haematuria is both sensitive
      and specific for detecting urinary schistosomiasis in endemic communities. The
      study also established that subjective haematuria offers a valid, easy to
      recognize target for morbidity control in endemic situation. It is proposed that
      with appropriate health education; availability of safe, effective, easy-to
      administer drugs, such as praziquantel, morbidity control of urinary
      schistosomiasis is feasible within the primary health care system with the lower
      cadre health worker or even a volunteer village health worker (VVHW) at the
      centre of the control effort.

PMID- 8757704
TI  - Two years of school injuries in a Scottish education sub-division.
AB  - Injuries sustained in schools account for 20-30% of all accident and emergency
      attendances in school age children. Little information has been available on the
      epidemiology of school accidents in the United Kingdom. Two years of routine
      school incident reports were analysed from Renfrew Sub-Region, an area with a
      school roll of 55,521 children attending 135 schools. Schools returned 1,660
      report forms in the two year period, of which 1,440 referred to injuries to
      school children. The peak incidence of injuries was in the 10-12 year age group.
      The male:female ratio was 1.37:1. Cuts/ laceration and fractures were the
      commonest diagnoses reported for both Primary and Secondary Schools. Injuries to
      face and features were commonest in Primary, and upper limb injuries in Secondary
      Schools. Uncontrolled areas, e.g. playgrounds, stairways and corridors were the
      most frequent places of occurrence in Primary Schools (Relative Risk 5.24, 95%
      C.I. 3.28-8.35). Report accuracy was assessed by comparing one year of school
      reports in a Local Government District to records in the local District General
      Hospital. This identified 156 children who had attended hospital as the result of
      a school accident. Schools overestimated the number of fractures by 27%, but
      where schools had not provided a diagnosis, 15.4% were identified as fractures in
      hospital records. Each child seen at the hospital received an average of 2.1 X
      rays. Nine children underwent manipulations under general anaesthetic. Seventeen
      children were admitted to hospital, and the group required 103 outpatient follow
      up appointments.

PMID- 8757705
TI  - How long is too long? Determining the early management of meningococcal disease
      in Birmingham.
AB  - OBJECTIVE: To determine the length of time cases of meningococcal disease wait
      before receiving parenteral antibiotic therapy in hospital. METHOD: The hospital
      case notes of residents of Birmingham who were admitted to local hospitals in
      1993 and discharged with a diagnosis of meningitis or meningococcal disease were
      reviewed. This information was combined with that held by the West Midlands
      Ambulance Service. RESULTS: Forty out of the 82 patients (49%) who met the case
      definition had meningococcal infection. Twenty one patients (26%) were admitted
      by ambulance, 11 of whom had meningococcal infection. The mean time from a
      request for an ambulance to the patient reaching hospital was 52 min for those
      with meningococcal infection compared to 55 min for those without. Nineteen
      patients (47.5%) with meningococcal infection waited more than one hour after
      admission for antibiotic treatment. Seven had an initial diagnosis of meningitis
      or meningococcal infection. Ten out of 27 patients with a meningococcal rash
      (37%), 13 out of 22 patients aged under five years (59%) and 13 out of 24
      patients with microbiologically confirmed meningococcal infection (54%) waited
      more than one hour for treatment. Seven patients with meningococcal infection
      received benzyl penicillin before admission. Six received hospital antibiotic
      treatment within the hour. CONCLUSION: The assumption that patients suspected of
      having meningitis or meningococcal disease are treated promptly once in hospital
      is not always correct. The results of this study reinforce the need for all
      doctors to give benzyl penicillin promptly to patients they suspect have
      meningococcal disease.

PMID- 8757706
TI  - Academicians' attitudes and beliefs towards anti-smoking measures.
AB  - Academic staff of Lucknow University (India) and its various faculties were
      questioned to know their attitudes and beliefs regarding various anti-smoking
      measures, using a questionnaire based on WHO guidelines. Of the male teachers
      21.4% were current smokers and 12.3% were ex-smokers. Non-smokers were in greater
      agreement with various anti-smoking measures than current and ex-smokers, while
      more females-all of whom were non-smokers-than their male counterparts supported
      these measures. Endorsement of various anti-smoking measures differed from group
      to group, however, academicians agreed most with the notion that "Everybody has a
      right to breath air free of tobacco smoke'. "Sale of tobacco completely banned'
      was the measure opposed by most of the academicians. "Preventing diseases' and
      "Religious reasons' were, respectively, the most and least important motives for
      not smoking.

PMID- 8757707
TI  - Blood donor centres can effectively publicise cancer screening.
AB  - The ability of the blood transfusion service to promote cancer screening using
      the uptake of colorectal cancer screening offered to blood donors as a model was
      measured. Blood donors were sent an explanation of colorectal cancer screening
      with their appointment time to give blood. Free faecal occult blood tests
      (Haemoccult) were offered by a doctor to donors who attended the Leicester Blood
      Donor Centre. 556 registered blood donors (309 men, 247 women) aged 51 to 65
      years were invited to donate blood over a three month period. Of the subjects who
      arrived to donate and accepted screening. 63% completed a faecal occult blood
      test with similar compliance in men and women (66% vs. 59%, chi 2 = 1.0, ns).
      Compliance was higher in older donors aged 61 to 65 years than those aged 51 to
      60 years in both men (90% vs. 60%, chi 2 = 7.0, P < 0.01) and women (87% vs. 51%,
      chi 2 = 6.2, P < 0.02). The proportion of the total target population screened,
      which included those donors invited to give blood but who did not attend was 21%.
      This approach successfully targeted donors who attended to give blood, although
      only a small proportion of the total target population was screened. Blood donor
      centres could display cancer screening and health promotion literature and
      encourage doctors supervising sessions to provide further information and advice
      to donors.

PMID- 8757708
TI  - Patient satisfaction at health centres in Trinidad and Tobago.
AB  - The aim of this paper is to identify background characteristics of health centre
      users in Trinidad and Tobago and their perceptions of the services provided.
      Multi-staged sampling was used to select 1,500 health centre users throughout the
      country. Data were obtained using structured interviews conducted on regular
      clinic days. Results show that there is an overwhelmingly large percentage of
      unemployed persons (80.4%) and women (75.9%) among the users of health centres.
      The elderly is well represented, with 25.4 percent of the sample being over 60
      years of age. Also, occupational status of family wage earners and educational
      attainment levels of respondents reflect a disproportionately higher number from
      lower socio-economic groupings among health centre users. On the other hand,
      proportions of different ethnic and religious groups among the respondents bear a
      striking similarity to the general population of Trinidad and Tobago. Respondents
      appear to be generally satisfied with the services of the health centres. When
      the categories for "satisfied' and "very satisfied' were combined, results show
      that 73.0% of respondents were satisfied with the comfort of the health centre,
      81.7% with the ease and convenience of getting to the health centre and 67.4%
      with the medical care received at the health centre. According to respondents'
      opinions, the services in greatest need of improvement are the pharmacy and
      doctor services, especially through reducing the long waiting period. When the
      doctors, nurses and pharmacists were compared with respect to "courtesy and
      consideration', "Skills and Competence' and "advice provided', results show that
      the generally high levels of satisfaction are remarkably similar in all three
      cases.

PMID- 8757709
TI  - Hospital admissions for chronic obstructive pulmonary disease in the population
      aged 55 years or over in Finland during 1972-1992.
AB  - Hospital admissions for patients with COPD (chronic obstructive pulmonary
      disease) as the primary diagnosis for the total Finnish population aged 55 years
      or over were collected from discharge register from 1972 to 1992. Numbers of
      admissions and days in hospital by sex and age in relation to total population
      and the duration of stay in hospital were analysed. A total of 188,570 admissions
      related to COPD were recorded. There was an average of 17.0 admissions per 1,000
      persons per year for men and 2.1 for women. The annual increase in the number of
      such periods, relative to population, was +1.5% for men (95% confidence interval
      +0.8 to +2.1%) and +5.1% (+4.0 to +6.2%) for women. A steady upward trend was
      found in all age groups among women and in the age group 65 years or over among
      men. The mean number of hospitalisation days increased among women but tended to
      decrease from the late 1980's onwards among men. The average length of stay
      decreased from 16.4 days (median: 11 days) in 1972 to 9.6 days (median: 7 days)
      in 1992. An increase in the need of hospital services was consistent feature
      among women and older men. Preceding smoking prevalence in Finland, ageing of the
      population and some institutional factors are the probable aspects behind this
      trend.

PMID- 8757710
TI  - Prostates and profits: the social construction of benign prostatic hyperplasia in
      American men.
AB  - Benign prostatic hyperplasia (BPH) is clinically diagnosed in approximately three
      fourths of American men, a prevalence two to three times higher than that
      currently reported in Scotland and Japan. Prostatectomy is the most common
      operation performed on American men over 65. A critical medical anthropological
      analysis reveals that American urologists rely on prostatectomy to maintain their
      practices, and the growth of urology as a specialty is significantly related to
      the 50% increase in the rate of surgery since 1965. Marketing campaigns and
      studies funded by pharmaceutical companies promote the perception of urinary
      difficulties as problematic, encourage men to medicalize their symptoms, and
      create demand for drug therapy and urologist treatment. The social construction
      of BPH as a progressive age-related disorder and the profit orientation of
      American medicine account for the elevated prevalence of BPH.

PMID- 8757711
TI  - Bonesetters and curers in a Mexican community: conceptual models, status, and
      gender.
AB  - In the indigenous Mexican village of Hueyapan, there is a clear contrast between
      the supernatural beliefs curers use to explain illness and the naturalistic
      assumptions made by this community's bonesetters. In addition to employing
      different conceptual models, the two types of healers differ with respect to
      their manner of recruitment, training, types of illnesses treated, social status,
      and gender. These differences add up to a seeming enigma: in a community where
      men largely control political, economic, and religious affairs, the higher status
      role of curer is undertaken most frequently by women and the lower status
      specialty of bonesetter by men. Hueyapan's health care system becomes less
      problematical, however, when it is recognized that recruitment to the bonesetter
      and curer roles is shaped by pragmatic considerations of role continuity and
      compatibility independent of the social status of these two occupations.

PMID- 8757712
TI  - Back to nature? Historical and cross-cultural perspectives on barriers to optimal
      breastfeeding.
AB  - This article examines the discrepancy between the recommendations of
      international authorities concerning breastfeeding and the practices of a
      significant proportion of women all over the world who discontinue breastfeeding
      because of the reported insufficiency of their milk. Our review of the evidence
      on the insufficient milk syndrome suggests that the phenomenon is inextricably
      linked to the construction of family, gender and motherhood at different
      historical times and in different parts of the world, and that the prevention of
      early discontinuation of breastfeeding requires a better understanding of these
      issues in their historical and cultural context.

PMID- 8757713
TI  - Contraceptive methods: do Hispanic adolescents and their family planning care
      providers think about contraceptive methods the same way?
AB  - This article describes how a family planning clinic-based program to prevent
      repeat pregnancy among Hispanic adolescents in Los Angeles used qualitative
      research to understand client contraceptive behavior. Background information on
      Hispanic adolescent reproductive patterns and an overview of paths to motherhood
      among teen clients are provided to contextualize the results. Participants sorted
      contraceptive methods on perceived similarities and ranked them on effectiveness,
      safety, and use-preference. Multidimensional scaling was used to identify and
      compare conceptual models. Both providers and teens grouped methods by
      effectiveness and mode of action, but acceptability and ease of method use were
      also important for teens. Providers found participation a worthwhile educational
      experience that facilitated self-reflection about their own biases and better
      understanding of their clients' needs. This method could be applied in many
      clinical settings where education and counseling are important in treatment and
      where patients and providers are likely to have different conceptual models
      regarding therapy.

PMID- 8757714
TI  - Purity, pollution and the invisible snake in southern Africa.
AB  - There exists in parts of southern and eastern Africa an apparently widespread
      belief in the existence of an invisible, internal "snake," often described as a
      power or force of some kind that dwells in the stomach but that can move
      throughout the upper body. Although some anthropologists have described this
      snake as related to witchcraft, findings from diverse parts of Mozambique, South
      Africa and elsewhere suggest that it may (also) be thought of as a symbolic
      expression of the need to respect the human body, specifically to protect it
      against the introduction of impurity. Belief in nyoka, as Tsonga- and Shona
      speakers call the invisible snake, suggests the importance of purity and
      pollution beliefs as they relate to health in a particular society; the presence
      of nyoka belief may even be taken as an empirical measure of their importance.
      Going beyond nyoka, it is argued that pollution beliefs are more central in
      southern African ethnomedicine than the literature suggests, perhaps more so than
      witchcraft and sorcery beliefs. It is hypothesized that pollution-related
      illnesses tend to be roughly coterminous with diseases biomedically classified as
      contagious. Apart from ethnographic and theoretical significance, establishing
      the nature and centrality of pollution beliefs, aided by analysis of cultural
      metaphors such as the invisible snake, can point to culturally appropriate ways
      of presenting health education messages in societies where pollution beliefs are
      important. Pollution beliefs may be characterized as quasi-naturalistic and they
      in fact represent an area of potential interface between indigenous and
      cosmopolitan medicine-far more than witchcraft beliefs.

PMID- 8757716
TI  - Humboldtian medicine.

PMID- 8757715
TI  - The making of a biochemist. I: Frederick Gowland Hopkins' construction of dynamic
      biochemistry.

PMID- 8757717
TI  - J C Prichard's concept of moral insanity--a medical theory of the corruption of
      human nature.

PMID- 8757718
TI  - Tropical medicine and bacteriology in Boston and Peru: studies of Carrion's
      disease in the early twentieth century.

PMID- 8757719
TI  - Thomas Mister of Shipston (1711-80).

PMID- 8757720
TI  - Pasteur and rabies: an interview of 1882.

PMID- 8757721
TI  - The biology of E colicins: paradigms and paradoxes.

PMID- 8757722
TI  - Comparative studies of chitinases A and B from Serratia marcescens.
AB  - Serratia marcescens produces several chitinolytic enzymes, including chitinase A
      (ChiA) and chitinase B (ChiB). In this study, ChiB was purified to homogeneity
      using a newly developed protocol based on hydrophobic interaction chromatography.
      Subsequently, characteristics of ChiB and of the hitherto only partly
      characterized ChiA were determined and compared. Pure ChiA and ChiB shared
      several characteristics such as a broad pH optimum around pH 5.0-6.0, and a
      temperature optimum between 50 and 60 degrees C. Both enzymes were fairly stable,
      with half-lives of more than 10 d at 37 degrees C, pH 6.1. Analyses of the
      degradation of various N-acetylglucosamine oligomers, fluorogenic substrates and
      colloidal chitin showed that both enzymes cleave chitobiose [(GlcNAc)2] from
      (GlcNAc)n and thus possess an exo-N,N'-diacetylchitobiohydrolase activity. Both
      enzymes were also capable of producing monomers from longer (GlcNAc)n substrates,
      indicating that they also have an endochitinase (ChiA) or exo-N,N',N"
      triacetylchitotriohydrolase (ChiB) activity. Kinetic analyses with 4
      methylumbelliferyl-beta-D-N,N'-diacetylchitobioside, an analogue of (GlcNAc)3,
      showed cooperative kinetics for ChiA, whereas for ChiB normal hyperbolic kinetics
      were observed. ChiA had a higher specific activity towards chitin than ChiB and
      synergistic effects on the chitin degradation rate were observed upon combining
      the two enzymes. These results, together with the results of sequence comparisons
      and previous studies of the cellular localization of the two chitinases in S.
      marcescens indicate possible roles for ChiA and ChiB in chitin breakdown.

PMID- 8757723
TI  - The localization of chitin synthase in membranous vesicles (chitosomes) in
      Neurospora crassa.
AB  - Polyclonal anti-chitin synthase antibodies raised against the Saccharomyces
      cerevisiae CHS2 gene product were used to identify and localize chitin synthase
      in the filamentous ascomycete Neurospora crassa. A single band of approximately
      110 kDa was observed in Western blots of total protein extracts of N. crassa,
      probed with these antibodies. However, several additional bands were labelled
      when membrane fraction proteins (microsomes) were probed. Histo-immunochemical
      localization of chitin synthase confirmed that the polypeptide is
      compartmentalized in membranous vesicles (chitosomes), which are abundant in the
      vicinity of the hyphal tip. TEM analysis did not reveal chitin synthase in the
      plasma membrane. However, dense labelling of membrane-associated chitin synthase
      was observed by light-microscopic analysis of N. crassa protoplasts and at young
      hyphal tips.

PMID- 8757724
TI  - Cell wall protein and glycoprotein constituents of Aspergillus fumigatus that
      bind to polystyrene may be responsible for the cell surface hydrophobicity of the
      mycelium.
AB  - Cell surface hydrophobicity (CSH) of Aspergillus fumigatus grown both in complex
      medium (yeast extract/peptone/dextrose; YPD) and minimal (Vogel's N) medium was
      monitored by assessing attachment of polystyrene microspheres to the cell
      surface. It was found that mature mycelium was hydrophobic. Treatment of intact
      mycelium with beta-mercaptoethanol (beta ME) abolished binding of the
      microspheres to hyphal elements, and coating of the microspheres with beta ME
      extracts from mycelium inhibited their attachment to intact mycelial cells. A.
      fumigatus mycelium was tagged in vivo with biotin and treated with beta ME. The
      beta ME extracts were analysed by SDS-PAGE and Western blotting with both
      peroxidase-conjugated-ExtrAvidin and concanavalin A (ConA). This procedure
      allowed identification of cell wall surface proteins and glycoproteins. Rabbit
      polyclonal antisera were raised against beta ME extracts obtained from cells
      grown in YPD and Vogel's N media. These antisera defined some major cell-wall
      bound antigens. SDS-PAGE and Western blotting analysis of the cell wall material
      released by beta ME and adsorbed on polystyrene microspheres revealed about 19
      protein species with apparent molecular masses ranging from 20 to 70 kDa, and two
      high-molecular-mass glycoproteins of 115 and 210 kDa. Treatment of cells grown in
      YPD, but not those grown in Vogel's N medium, with beta ME released a 55 kDa
      polypeptide able to adsorb to polystyrene microspheres that was detectable with
      the antisera. The ability to bind to polystyrene particles exhibited by several
      protein and glycoprotein species released by beta ME treatment suggested that
      these cell wall moieties possess exposed hydrophobic domains that could be
      responsible for the CSH of mycelium.

PMID- 8757725
TI  - Sequence analysis and regulation of a gene encoding a cuticle-degrading serine
      protease from the nematophagous fungus Arthrobotrys oligospora.
AB  - The nematode trapping fungus Arthrobotrys oligospora produces an extracellular
      serine protease (designated PII) that immobilizes free-living nematodes in
      bioassays and hydrolyses proteins of the nematode cuticle. Peptides were isolated
      from PII and partly sequenced. Three internal peptide sequences were used to
      design synthetic oligonucleotides, which allowed the subsequent isolation of the
      gene encoding PII from a genomic library. The deduced amino acid sequence
      indicated that PII is synthesized as a preproenzyme containing the mature enzyme,
      a signal sequence and a propeptide that are removed before the enzyme is secreted
      into the medium. The primary sequence of PII displayed a high degree of
      similarity with several other serine proteases of ascomycetes belonging to the
      subtilisin family. Northern analysis demonstrated that PII was expressed when the
      fungus was starved of nitrogen and carbon and that the expression was
      significantly stimulated by the addition to the medium of various soluble and
      insoluble proteins, including fragments of nematode cuticle. The levels of the
      mRNA as well as the proteolytic activity of PII were repressed in the presence of
      more easily metabolized forms of nitrogen (including ammonia, nitrate and amino
      acids) or glucose. The activity of the enzyme was almost completely inhibited by
      the peptide Phe-Val, as well as by the amino acid Phe, without a corresponding
      decrease in mRNA level. Notably, peptides with similar structures are known to be
      secreted by the host (nematode) and to stimulate the production of infection
      structures (traps) of the fungus.

PMID- 8757726
TI  - Mutagenesis of three surface-exposed loops of a Bacillus thuringiensis
      insecticidal toxin reveals residues important for toxicity, receptor recognition
      and possibly membrane insertion.
AB  - Information on the molecular determinants of receptor recognition, membrane
      insertion and toxin pore-formation was sought by making 42 single and multiple
      substitutions of residues 312-314 (GYY), 367-370 (YRRP) and 438-441 (SGFS) in the
      Bacillus thuringiensis insecticidal CrylAc delta-endotoxin by site-directed
      mutagenesis. These three regions correspond to three putative surface-exposed
      loops (loops 1, 2 and 3, respectively) in domain II of the delta-endotoxin,
      forming the molecular apex of the structure. All except mutants GFY (loop 1),
      YKRA, SRRA, YRKA (loop 2) and TGFS (loop 3) expressed delta-endotoxin protein at
      wild-type levels which was stable upon activation by Pieris brassicae gut extract
      or trypsin. Toxicity assays for all the fully stable mutants using Manduca sexta
      larvae showed that G312, Y367, R368, R369, S438 and G439 are important for
      activity. Wild-type toxin was then labelled in vivo with [35S]methionine and
      heterologous competition binding assays were carried out for all the mutants
      using brush border membrane vesicles prepared from Manduca sexta midgut. Most and
      least conservative mutations of G439 and least conservative substitutions of
      Y367, R368 and R369 reduced the ability of the toxin to bind competitively. The
      most conservative mutation, S441T, gave significantly increased binding. These
      results suggested that these four residues play a role in the initial receptor
      binding step in the toxin mechanism. As no significant effect on binding affinity
      was observed in relatively non-toxic mutants in which residues G312 and S438 were
      mutated, we suggest that these residues are involved in the subsequent steps of
      membrane insertion and pore-formation.

PMID- 8757727
TI  - Lysine-induced premature transcription termination in the lysC operon of Bacillus
      subtilis.
AB  - The expression of the Bacillus subtilis lysC operon, which encodes the first
      specific enzyme of lysine biosynthesis, is controlled by the availability of the
      end product, lysine. The question of whether lysine exerts its control by
      inducing premature termination of transcription was addressed using Northern blot
      analysis. Whereas lys-C-specific RNA from lysine-starved B. subtilis consisted
      primarily of the expected full-length mRNA (1.6 kb), that from bacteria grown
      with an excess of lysine consisted of a truncated 0.27 kb RNA in place of the
      full-length 1.6 kb transcript. On the other hand, a B. subtilis aecA mutant, in
      which the lysC operon was derepressed owing to a single nucleotide substitution
      in the region corresponding to the lysC leader transcript, produced full-length
      lysC mRNA, but no 0.27 kb RNA, even during growth with excess lysine. Mapping of
      the truncated 0.27 kb lysC RNA by hybridization with oligonucleotide probes
      showed that it corresponded to the upstream portion of the lysC leader
      transcript, extending from the transcription initiation site to a putative rho
      independent terminator element. Quantitative transcript analysis by hybridization
      with specific oligonucleotides showed that lysine did not affect the number of
      lysC-specific RNA molecules but promoted the stoichiometric replacement of full
      length mRNA with truncated 0.27 kb molecules. These results indicate that lysine
      regulates the expression of the lysC operon by effecting the premature
      termination of transcription at a rho-independent terminator site in the lysC
      leader region and that the site of the aecA mutation, far upstream of the
      putative terminator element, must play an essential role in premature
      transcription termination by a mechanism which is not yet understood.

PMID- 8757728
TI  - The genes of lepA and hemN form a bicistronic operon in Bacillus subtilis.
AB  - The IepA operon of Bacillus subtilis was found to be bicistronic and to consist
      of the two genes IepA and hemN, which encode a putative GTP-binding protein and
      an oxygen-independent coproporhyrinogen III oxidase, respectively. The IepA
      operon is located immediately upstream of the dnaK operon. Both operons are
      transcribed in the same direction and are not separated by an obvious
      transcription-terminator-like structure. The IepA operon is preceded by a
      potential vegetative promoter, and there is a putative strong intergenic
      terminator between IepA and hemN. Northern blot experiments revealed only a
      transcript corresponding to IepA, but expression of hemN was demonstrated in slot
      blot and immunoblot experiments using antibodies raised against His-tagged HemN.
      The data suggest that most of the transcripts originating at the potential
      vegetative promoter are terminated at the intergenic terminator. Readthrough
      transcription into the downstream dnaK operon was not found.

PMID- 8757729
TI  - The Bacillus stearothermophilus NUB36 surA gene encodes a thermophilic sucrase
      related to Bacillus subtilis SacA.
AB  - The complete nucleotide sequence of the surA gene, encoding a sucrase from
      Bacillus stearothermophilus NUB36, was determined. surA was composed of 1338 bp
      and encoded 445 amino acid residues. The deduced polypeptide of M(r) 51519 showed
      strong sequence similarity to sucrose and sucrose phosphate hydrolases from
      Bacillus subtilis, Klebsiella pneumoniae and Vibrio alginolyticus, and contained
      the 'sucrose box' residues thought to be important for catalysis of the transfer
      of fructose from sucrose. The enzyme was partially purified using affinity
      chromotography from extracts of Escherichia coli containing the cloned surA. SurA
      displayed an optimum temperature for sucrose hydrolysis of 55 degrees C and high
      stability. The M(r) of SurA determined by gel filtration was 105,000, which
      suggested that the active form of the enzyme is a dimer. SurA exhibited an
      apparent Km of 40 mM for sucrose but, unlike the homologous B. subtilis enzyme,
      had no detectable sucrose phosphate hydrolase activity.

PMID- 8757730
TI  - The bglX gene located at 47.8 min on the Escherichia coli chromosome encodes a
      periplasmic beta-glucosidase.
AB  - A new Escherichia coli gene, bgIX, encoding a beta-D-glucosidase (EC 3.2.1.21)
      has been characterized. The bgIX gene is located adjacent to the dld gene at 47.8
      min or 2225 kb on the E. coli chromosome. The sequence of a 2.6 kb DNA fragment
      from this region revealed a large open reading frame encoding a protein of 765
      amino acids. The BgIX protein was purified from the periplasm, and amino-terminal
      sequencing suggests that the mature protein is derived from cleavage of a 20
      residue signal peptide. A search of the sequence databases revealed that BgIX is
      a member of a large family of beta-glucosidases from a variety of bacteria and
      fungi, and the plant Arabidopsis thaliana. It differs from the other four E. coli
      phospho-beta-glucosidases in sequence and in its periplasmic rather than
      cytoplasmic location. The BgIX enzyme has a Km of 18 +/- 1 mM and a Vmax of 3 +/-
      0.7 mumol min-1 for the colorimetric substrate o-nitrophenyl beta-D
      glucopyranoside.

PMID- 8757731
TI  - Partial deletion of the Saccharomyces cerevisiae GDH3 gene results in novel
      starvation phenotypes.
AB  - A small-scale functional analysis screen has revealed several new phenotypes
      associated with a large deletion of GDH3, one of two Saccharomyces cerevisiae
      genes known to encode NADP-linked glutamate dehydrogenase. Diploids heterozygous
      for the deletion are able to sporulate in rich media, while haploid deletants
      produce dark, wrinkled colonies containing pseudohyphal cells. The haploid cells
      rapidly lose viability upon starvation.

PMID- 8757732
TI  - Analysis of starvation conditions that allow for prolonged culturability of
      Vibrio vulnificus at low temperature.
AB  - The response of the estuarine human pathogen Vibrio vulnificus to starvation for
      carbon, nitrogen or phosphorus, or all three nutrients simultaneously (multiple
      nutrient), was examined with respect to the maintenance of culturability during
      incubation at low temperature. V. vulnificus showed similar survival patterns
      during starvation for the individual nutrients when kept at 24 degrees C. On the
      other hand, cultures prestarved at 24 degrees C and then shifted to 5 degrees C
      maintained culturability at low temperature in a starvation-condition-dependent
      manner. Carbon and multiple-nutrient starvation were indistinguishable in their
      ability to mediate maintenance of culturability in the cold. Prolonged starvation
      for phosphorus had a similar effect, but nitrogen starvation did not allow for
      maintenance of culturability. Extracellular factors produced during starvation
      were not observed to have an effect on the culturability of cells incubated at
      low temperature. Protein synthesis during starvation for individual nutrients was
      analysed by two-dimensional PAGE of pulse-labelled proteins. Carbon and multiple
      nutrient starvation gave nearly identical protein induction patterns involving at
      least 34 proteins, indicating that carbon starvation determines both responses.
      Nitrogen starvation for 1 h induced 24 proteins, while phosphorus starvation
      induced a set of 10 proteins after 1 h and about 40 proteins after 18 h. It is
      suggested that starvation for carbon or phosphorus induces maintenance of
      culturability of V. vulnificus incubated at low temperature via the synthesis of
      distinct sets of starvation-specific proteins.

PMID- 8757733
TI  - Analysis of heat shock gene expression in Lactococcus lactis MG1363.
AB  - The induction of the heat shock response in Lactococcus lactis subsp. cremoris
      strain MG1363 was analysed at the RNA level using a novel RNA isolation procedure
      to prevent degradation. Cloning of the dnaJ and groEL homologues was carried out.
      Northern blot analysis showed a similar induction pattern for dnaK, dnaJ and
      groELS after transfer from 30 degrees C to 43 degrees C when MG1363 was grown in
      defined medium. The dnaK gene showed a 100-fold induction level 15 min after
      temperature shifting. Induction of the first two genes in the dnaK operon, orf1
      and grpE, resembled the pattern observed for the above genes, although maximum
      induction was observed earlier for orf1 and grpE. Novel transcript sizes were
      detected in heat-shocked cells. The induction kinetics observed for ftsH
      suggested a different regulation for this gene. Experimental evidence for a
      pronounced transcriptional regulation being involved in the heat shock response
      in L. lactis MG1363 is presented. A gene located downstream of the dnaK operon in
      strain MG1363, named orf4, was shown not to be regulated by heat shock.

PMID- 8757734
TI  - Acid tolerance in Rhizobium meliloti strain WSM419 involves a two-component
      sensor-regulator system.
AB  - An acid-sensitive mutant, TG5-46, derived from Rhizobium meliloti WSM419 by Tn5
      mutagenesis, fails to grow below pH 6.0 whereas the parent strain grows at pH
      5.7. The DNA sequence of a 2.2 kb rhizobial DNA region flanking Tn5 in TG5-46
      contains two open reading frames, ORF1 (designated actS) and ORF2 (designated
      actR), having high similarity to the sensor-regulator pairs of the two-component
      systems involved in signal transduction in prokaryotes. Insertion of an omega
      interposon into actS in R. meliloti WSM419 resulted in an acid-sensitive
      phenotype. A DNA fragment from the wild-type complemented the acid-sensitive
      phenotype of RT295 (ActS-) and TG5-46 (ActR-), while fragments containing only
      actR or actS complemented TG5-46 and RT295, respectively. The presence of
      multiple copies of actR complemented not only TG5-46 but also RT295. Cloning DNA
      upstream from actR and actS into a broad-host-range lacZ expression vector and
      measuring beta-galactosidase activities showed that both genes are constitutively
      expressed regardless of the external pH. Genomic DNA from all strains of R.
      meliloti, but no other bacteria tested, hybridized with an actRS probe at high
      stringency. These data implicate a two-component sensor-regulator protein pair in
      acid tolerance in R. meliloti and suggest their involvement in pH sensing and/or
      response by these bacteria.

PMID- 8757735
TI  - Diversity of repC plasmid-replication sequences in Rhizobium leguminosarum.
AB  - Homologues of the plasmid replicator gene repC were detected and characterized in
      a sample of Rhizobium leguminosarum strains. Conserved PCR primers were designed
      from published sequences of repC; they amplified a fragment of about 750 bp from
      39 out of 41 strains tested, and also from several Sinorhizobium strains,
      including S. meliloti. Restriction endonuclease digestion showed that the PCR
      product from individual strains, though uniform in size, was often heterogeneous
      in sequence. PCR products from 24 field isolates of R. leguminosarum from France,
      Germany and the UK were cloned and partially sequenced from both ends.
      Phylogenies constructed from the 5' and 3' ends (200 bp each) were largely
      congruent and demonstrated four clearly defined groups plus several unique
      strains. Published Agrobacterium repC sequences fall within the phylogeny of R.
      leguminosarum sequences, though not within any of the four groups. Specific pairs
      of PCR primers were designed for each of the four groups; 29 out of 41 R.
      leguminosarum strains gave a PCR product of the expected size with more than one
      group-specific primer pair. We hypothesize that the sequence groups correspond to
      incompatibility groups of Rhizobium plasmids.

PMID- 8757736
TI  - Influence of salt on the transcription of the gas-vesicle genes of Haloferax
      mediterranei and identification of the endogenous transcriptional activator gene.
AB  - The transcription of the 14 gvp genes of the gas-vesicle-encoding mc-vac region
      was investigated, using RNA from 25% and 15% (w/v) salt cultures of the
      moderately halophilic archaeon Haloferax mediterranei. Transcription occurred
      only from two promoters, located in front of the mc-gvpA and mc-gvpD genes. In
      both cultures transcripts spanning the entire mc-gvpDEFGHIJKLM transcription unit
      were formed only during the exponential growth phase. Amounts of these
      transcripts were larger in the 25% salt culture, in which the 2.0 kb mc-gvpD
      transcripts were also synthesized during the stationary phase. The levels of the
      mc-gvpD transcripts and of the 324 nt mc-gvpA mRNA increased in parallel during
      the stationary phase of the 25% salt culture. Only under these conditions were
      mRNAs spanning the entire mc-gvpACNO transcription unit observed, and gas
      vesicles were formed. Investigation of the influence of the mc-gvpDE genes on
      both mc-vac promoters in transformants revealed that by themselves they were
      nearly inactive. The addition of mc-gvpE, however, resulted in a high level of
      constitutively produced mc-gvpA and mc-gvpD mRNA, indicating a transcriptional
      activator function for the mc-gvpE product.

PMID- 8757737
TI  - Active transport of glucosylglycerol is involved in salt adaptation of the
      cyanobacterium Synechocystis sp. strain PCC 6803.
AB  - An active-transport system for the osmoprotective compound glucosylglycerol (GG)
      was found in the cyanobacterium Synechocystis sp. strain PCC 6803. Uptake assays
      with 14C-labelled GG showed that the GG transport was enhanced in cells adapted
      to increasing concentrations of NaCl. Kinetic studies indicated a Michaelis
      Menten relationship. The uptake of GG was energy dependent and occurred against a
      steep concentration gradient. It was inhibited by uncouplers as well as by a
      combination of darkness and KCN. The affinity of the transporter seems to be
      restricted to osmoprotective compounds of cyanobacteria; from a variety of
      compounds tested only sucrose and trehalose competed with GG for uptake. A salt
      sensitive mutant of Synechocystis 6803 unable to synthesize GG could be
      complemented to salt resistance by exogenous GG. Accumulation of GG from the
      medium was essential for the restoration of photosynthesis and growth in mutant
      cells under high-salt conditions. In wild-type cells, the GG transporter probably
      serves to prevent GG leaking out of salt-stressed cells.

PMID- 8757738
TI  - Binding-protein-dependent arginine transport in Pasteurella haemolytica.
AB  - A periplasmic arginine transport system that is a member of the ATP -dependent
      transport superfamily was identified in Pasteurella haemolytica. The gene
      encoding the periplasmic binding protein (lapT) was cloned and the protein
      overexpressed in Escherichia coli. LapT was purified to homogeneity using a
      modified osmotic shock procedure and anion-exchange column chromatography. Filter
      binding assays established that LapT is an L-arginine-binding protein. Various
      amino acids were tested for their ability to inhibit L-arginine binding to LapT.
      When present in 100-fold excess, only L-arginine, D-arginine and citrulline
      competed with L-arginine for binding. Arginine transport in P. haemolytica whole
      cells was competitively inhibited by the same amino acids, suggesting that the
      LapT permease specifically transports L-arginine. The dissociation constant for
      the L-arginine-LapT complex was 170 nM and the stoichiometry of binding was
      approximately 0.8 mol L-arginine (mol LapT)-1. A polyclonal antibody raised
      against the purified protein permitted detection of LapT in P. haemolytica
      periplasmic fractions.

PMID- 8757739
TI  - A cb-type cytochrome-c oxidase terminates the respiratory chain in Helicobacter
      pylori.
AB  - A Helicobacter pylori membrane fraction oxidized yeast and equine cytochrome c,
      and N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD). When ascorbate was used as
      reductant, the Vmax and apparent Km values were 612 nmol electron min-1 (mg
      protein)-1 and 14 microM for yeast, and 419 nmol electron min-1 (mg protein)-1
      and 19 microM for equine cytochrome c, respectively. For TMPD oxidation, the Vmax
      and Km values were 640 nmol electron min-1 (mg protein)-1 and 182 microM,
      respectively. These oxidase activities showed a high affinity for oxygen.
      Inhibition of both cytochrome-c and TMPD oxidase activities by 50% was caused by
      about 4 microM cyanide and about 0.5 mM azide. Redox difference spectra of the
      membrane solubilized with Triton X-100 showed b- or c-type cytochromes but not
      aa3-type cytochromes. c-type and a part of some b-type cytochromes were reduced
      with ascorbate plus TMPD. A CO difference spectrum revealed that protohaem, but
      not an aa3-type cytochrome, may be interacting with CO/oxygen. Only protohaem was
      detected in the haem fraction extracted from the membrane. Three polypeptides
      (60, 38 and 29 kDa) were found to be bearing haem c after SDS-PAGE of the
      membrane. From these results, it was suggested that the cbb3-type cytochrome-c
      oxidase, having a haem-copper binuclear centre like the cytochrome aa3-type
      oxidase, but differing in a few other properties, functions as a terminal oxidase
      in the respiratory chain of H. pylori.

PMID- 8757740
TI  - The Cdc25 protein of Saccharomyces cerevisiae is required for normal glucose
      transport.
AB  - The essential CDC25 gene product of Saccharomyces cerevisiae is the most upstream
      known component of the RAS/adenylate cyclase pathway. Cdc25 is a GTP-exchange
      protein involved in activating RAS in response to fermentable carbon sources. In
      this paper it is reported that the Cdc25 protein, in addition to its stimulatory
      role in the RAS/adenylate cyclase pathway, regulates glucose transport.
      Continuous culture studies and glucose uptake experiments showed that the cdc25-1
      and the cdc25-5 temperature-sensitive mutants exhibit decreased glucose uptake
      activity at the restrictive temperature under both repressed and derepressed
      conditions as compared to the wild-type strain. Because the cdc25-1 mutant is not
      impaired in its cAMP metabolism, it is concluded that this effect on glucose
      transport is independent of cAMP levels. Furthermore, it is shown that the
      decrease in glucose uptake activity is not due to a decrease in protein synthesis
      or to an arrest in the G1 phase of the cell cycle. In addition to a defect in
      glucose uptake, the cdc25-5 mutant strain exhibited differences in glucose
      metabolism, probably due to the decreased cAMP level and hence decreased protein
      kinase A activity. Because the Cdc25 protein is localized at the membrane, these
      results indicate that Cdc25 is directly involved in glucose transport and may be
      in direct contact with the glucose transporters.

PMID- 8757741
TI  - Glucose-triggered signalling in Saccharomyces cerevisiae: different requirements
      for sugar phosphorylation between cells grown on glucose and those grown on non
      fermentable carbon sources.
AB  - Addition of glucose or fructose to cells of the yeast Saccharomyces cerevisiae
      grown on a nonfermentable carbon source triggers within a few minutes
      posttranslational activation of trehalase, repression of the CTT1 (catalase) and
      SSA3 (Hsp70) genes, and induction of the ribosomal protein genes RPL1, RPL25 and
      RPS33. By using appropriate sugar kinase mutants, it was shown that rapid glucose
      or fructose-induced activation of trehalase requires phosphorylation of the
      sugar. On the other hand, partial induction of RPL1, RPL25 and RPS33 as well as
      partial repression of CTT1 and SSA3 were observed in the absence of sugar
      phosphorylation. In glucose-grown nitrogen-starved yeast cells readdition of a
      nitrogen source triggers activation of trehalase in a glucose- or fructose
      dependent way, but with no apparent requirements for phosphorylation of the
      sugar. Repression of CTT1 and SSA3 under the same conditions was also largely
      dependent on the presence of the sugar and also in these cases there was a strong
      effect when the sugar could not be phosphorylated. Nitrogen induction of RPL1,
      RPL25 and RPS33 was much less dependent on the presence of the sugar, and only
      phosphorylated sugar caused a further increase in expression. These results show
      that two glucose-dependent signalling pathways, which can be distinguished on the
      basis of their requirement for glucose phosphorylation, appear to be involved in
      activation of trehalase, repression of CTT1 and SSA3 and induction of ribosomal
      protein genes. They also show that nutrient-induced repression of CTT1 and SSA3
      is not a response to improvement of the growth conditions because the addition of
      nonmetabolizable sugar does not ameliorate the growth conditions. Similarly, the
      upshift in ribosomal protein synthesis cannot be a response to increased
      availability of energy or biosynthetic capacity derived from glucose, but it is
      apparently triggered to a significant extent by specific detection of glucose as
      such.

PMID- 8757742
TI  - Trypsin-like protease of Streptomyces exfoliatus SMF13, a potential agent in
      mycelial differentiation.
AB  - Streptomyces exfoliatus SMF13 sequentially produced leupeptin, leupeptin
      inactivating enzyme (LIE) and trypsin-like protease (TLP). TLP was produced upon
      exhaustion of glucose. Autolysis of mycelium was accompanied by an increase in
      TLP activity. However, in three bld mutants isolated from S. exfoliatus SMF13
      after UV-mutagenesis, mycelium autolysis did not occur, and neither LIE nor TLP
      was produced, although leupeptin was produced. Production of both LIE and TLP was
      restored in a spontaneous Spo+ revertant of a bld mutant. In contrast, two whi
      mutants sequentially produced leupeptin, LIE and TLP. The molecular mass of TLP
      produced during morphological differentiation was estimated to be 31.8 kDa by SDS
      PAGE. The N-terminal amino acid sequence was RVGGTxAAQGNFPFQQxLSM. TLP was
      competitively inhibited by leupeptin; the inhibition constant was 0.015 microM.
      TLP effectively hydrolysed the mycelial protein extract of S. exfoliatus SMF13,
      but the hydrolytic activity was inhibited by leupeptin. It was concluded that
      morphological differentiation and production of TLP are coordinately regulated,
      that TLP may function as an enzyme in the metabolism of mycelial proteins, and
      that the hydrolytic activity of TLP is regulated by autogenous leupeptin in S.
      exfoliatus SMF13.

PMID- 8757743
TI  - Flux limitations in the ortho pathway of benzoate degradation of Alcaligenes
      eutrophus: metabolite overflow and induction of the meta pathway at high
      substrate concentrations.
AB  - The growth behaviour of Alcaligenes eutrophus using various concentrations of
      benzoate was investigated. In batch culture, growth was exponential and growth
      rate (mu) and yields (Y) were high [mu = 0.51 h-1 and Yx/benzoate = 0.56 mol
      carbon (mol carbon)-1] when low concentrations of benzoate (< 5 mM) were used.
      These kinetic parameters were close to the maxima determined in a benzoate
      limited chemostat [mu(max) = 0.55 h-1 and YX/benzoatemax = 0.57 mol carbon (mol
      carbon)-1] and the part of the energy for maintenance was limited (mATP = 4.3 +/-
      2.2 mmol ATP g-1 h-1). When higher concentrations of benzoate were used (up to 40
      mM), several metabolic limitations appeared. The specific rate of benzoate
      consumption was not altered, whereas growth was inhibited [Ki(benzoate)
      approximately 27 mM]. Furthermore, high concentrations of catechol together with
      some 1,2-dihydro-1,2-dihydroxybenzoate (DHB) transiently accumulated in the
      medium. The accumulation of catechol was attributed to limiting flux through
      catechol 1,2-dioxygenase estimated to be 5.2 mmol g-1 h-1, whereas that of DHB
      was provoked by an imbalance in the NADH/NAD+ intracellular content. The direct
      consequence of DHB accumulation was the induction of the meta pathway for the
      degradation of catechol, and this pathway contributed up to 20% of the total flux
      of catechol to the central metabolism. Finally, when very high concentrations of
      benzoate were used (55 mM), both growth and the specific rate of benzoate
      degradation were diminished due to a strong decrease in benzoate 1,2-dioxygenase
      specific activity.

PMID- 8757744
TI  - RNA polymerase, PurR and MetR interactions at the glyA promoter of Escherichia
      coli.
AB  - In Escherichia coli, the MetR and PurR proteins positively and negatively
      regulate glyA gene expression, respectively. A DNase I footprint analysis showed
      that both proteins bind independently to the glyA control region. The PurR
      protein blocks RNA polymerase (RNAP) from binding to the glyA promoter. The
      presence of hypoxanthine, the co-repressor of PurR, increases the ability of PurR
      to prevent RNAP binding, providing a model for repression of the glyA gene by
      PurR. In contrast, MetR alters the RNAP footprint pattern of the glyA control
      region. In addition, the MetR footprint is increased in the presence of RNAP,
      suggesting that the two proteins might interact.

PMID- 8757745
TI  - IS1236, a newly discovered member of the IS3 family, exhibits varied patterns of
      insertion into the Acinetobacter calcoaceticus chromosome.
AB  - Analysis of spontaneous mutations in Acinetobacter calcoaceticus revealed a 1237
      bp insertion sequence named IS1236 and possessing a nucleotide sequence
      resembling those of members of the lS3 family. The chromosome of A. calcoaceticus
      strain ADP1 contains seven copies of IS1236 which appears to insert
      preferentially into pobR, the transcriptional activator of the structural gene
      for p-hydroxybenzoate hydroxylase. IS1236 creates tandem 3 bp DNA duplications
      flanking the sites of its insertion in pobR. Different duplication patterns are
      found following insertion of IS1236 into pcaH, a structural gene for
      protocatechuate 3,4-dioxygenase. Therefore the insertion of properties of IS1236
      appear to be influenced by its DNA target. Amino acid sequences associated with
      the apparent transposase function have been conserved in ORFB of IS1236 whereas
      the presumed DNA-binding helix-turn-helix region of IS1236 ORFA exhibits
      substantial amino acid sequence divergence from its IS3 counterparts. IS1236 ORFA
      and ORFB coding sequences overlap considerably, and sequence evidence indicates
      mechanisms for ORFB expression in IS1236 may resemble those employed by other
      members of the IS3 family. Portions of the IS1236 terminal repeats exhibit
      substantial sequence divergence from other members of the IS3 family, but
      evolution appears to have conserved a mechanism preventing expression of the
      insertion sequence genes as a consequence of transcriptional readthrough.

PMID- 8757746
TI  - Transcriptional regulation of the Escherichia coli rhaT gene.
AB  - Transcriptional regulation of the rhaT gene, one of the operons forming the
      rhamnose regulon in Escherichia coli, was studied by fusing its complete or
      deleted promoter to the reporter gene lacZ. Analysis of beta-galactosidase
      activities induced in these constructions grown under different conditions
      predicted the presence of two putative control elements: one for the RhaS
      regulatory protein and activating the gene not only by L-rhamnose but also by L
      lyxose or L-mannose, the other for cAMP-catabolite repression protein and
      activating this gene in the absence of glucose. Anaerobiosis increased the
      promoter function two- to threefold with respect to the aerobic condition.
      Experiments involving complementation of strains containing the rhaT-promoter
      fusion and carrying a deletion in the rhaS and/or rhaR genes with plasmids
      bearing the rhamnose regulatory genes showed that rhaT is controlled by a
      regulatory cascade, in which RhaR induces rhaSR and the accumulated RhaS directly
      activates rhaT.

PMID- 8757747
TI  - Complementation of the hha mutation in Escherichia coli by the ymoA gene from
      Yersinia enterocolitica: dependence on the gene dosage.
AB  - The Hha protein from Escherichia coli is highly similar (82%) to the YmoA protein
      from Yersinia enterocolitica. Both are members of a new class of proteins that
      modulates gene expression, probably by influencing DNA topology. In this paper,
      complementation of the hha mutation in E. coli by the ymoA gene from Y.
      enterocolitica has been studied. We show that the ymoA gene complements one of
      the phenotypic properties of hha mutants (high level of haemolysin production
      when they carry the recombinant plasmid pANN202-312) when cloned in a medium-copy
      number plasmid but not when carried in a low-copy-number plasmid. Western blot
      analysis of the expression of YmoA in E. coli rules out inefficient expression of
      the protein. Surprisingly, the hha gene itself fails to complement the hha
      mutation when cloned in a medium-copy-number vector and causes genetic
      rearrangements of the E. coli chromosome as a consequence of insertion sequences
      mobilization.

PMID- 8757748
TI  - An aroA mutant of Yersinia pestis is attenuated in guinea-pigs, but virulent in
      mice.
AB  - This study describes a PCR-based approach for the production of a rationally
      attenuated mutant of Yersinia pestis. Degenerate primers were used to amplify a
      fragment encoding 91.45% of the aroA gene of Y. pestis MP6 which was cloned into
      pUC18. The remainder of the gene was isolated by inverse PCR. The gene was
      sequenced and a restriction map was generated. The Y. pestis aroA gene had 75.9%
      identity with the aroA gene of Yersinia enterocolitica. The cloned gene was
      inactivated in vitro and reintroduced into Y. pestis strain GB using the suicide
      vector pGP704. A stable aro-defective mutant. Y. pestis GB aroA, was isolated and
      its virulence was examined in vivo. The mutant was attenuated in guinea-pigs and
      capable of inducing a protective immune response against challenge with the
      virulent Y. pestis strain GB. Unusually for an aro-defective mutant, the Y.
      pestis aroA mutant was virulent in mice, with a median dose which induced
      morbidity of death similar to that of the wild-type, although time to death was
      significantly prolonged.

PMID- 8757749
TI  - Analysis of putative ABC transporter genes in Mycoplasma hyopneumoniae.
AB  - A previously described DNA probe specific for Mycoplasma hyopneumoniae (I-141)
      was fully sequenced and found to consist of 1618 bp and to contain two tandemly
      repeated ORFs. The deduced amino acid sequence of the two ORFs showed significant
      homologies with ATP-binding cassette (ABC) transporter proteins, particularly
      those of the eukaryotic multidrug resistance (MDR) protein family (up to 21%
      identity and 47% similarity). A somewhat lower homology was evident with the
      secretion protein HlyB of the RTX-haemolysin from Escherichia coli. The location
      of the two ORFs on the M. hyopneumoniae chromosome was downstream of the rrl gene
      encoding the 23S rRNA, but transcribed in the opposite direction. PCR
      amplification and subsequent chromosomal analysis by Southern blot hybridization
      of several M. hyopneumoniae strains showed that all field strains contained the
      two putative ABC transporter genes. However, some culture collection strains
      derived from strain J had lost these genes as the result of a 2221 bp deletion.

PMID- 8757750
TI  - Immunoelectron microscopic localization of variable proteins on the surface of
      Mycoplasma bovis.
AB  - The ultrastructural distribution and immunological accessibility of the variable
      surface proteins VspA, VspB, VspC and VspD were determined by immunoelectron
      microscopy on the surface of negatively stained cells of Mycoplasma bovis PG45
      and 18 subclones, expressing either one or two of the Vsps. The variable proteins
      VspA, VspB, VspC and VspD, recognized by two monoclonal antibodies (mAb 1E5 and
      mAb 87-2) and visualized by goat-anti-murine-lgM labelled with gold particles,
      showed identical distribution patterns on the surfaces of the cells of all M.
      bovis clones investigated. Gold particles were distributed over the whole cell
      surface, arranged in clusters. The cell form seemed not to have an influence on
      the decoration pattern. Gold particles were also observed in irregular
      distributions around the cells. All clones showed unlabelled cells as well as
      strongly and weakly labelled cells. There were in general, however, no
      significant differences in the percentages of unlabelled, weakly labelled and
      strongly labelled cells, either between clones expressing different Vsps or
      between individual clones. No correlations were found between the numbers of
      labelled cells in immunoelectron microscopy and the numbers of labelled colonies
      in immunobinding assay (IBA) originating from the same broth cultures. The
      percentage of positive colonies in IBA was generally much higher than the
      percentage of positive cells in immunoelectron microscopy. The results show that
      the cells of the M. bovis clones are not identical, but differ in their surface
      antigens, and reveal the high variable potential of this species.

PMID- 8757751
TI  - A reappraisal of the diversity and class distribution of aspartate
      transcarbamoylases in gram-negative bacteria.
AB  - Recently, the subunit composition of class A aspartate transcarbamoylases
      (ATCases) in fluorescent pseudomonads has been clarified. We present evidence
      that distribution of this type of ATCase may be more widespread than at first
      suspected. Bacterial ATCases exist in three forms: class A (molecular mass
      approximately 450-500 kDA); class B, typified by Escherichia coli ATCase
      (approximately 300 kDa); and class C, typified by Bacillus subtilis ATCase
      (approximately 100 kDa). Using gradient gel electrophoresis with activity
      staining to scan bacterial sonicates, we report the existence of six more class
      ATCases. We have purified one of these, Acinetobacter calcoaceticus ATACase, and
      found its subunit composition to be similar to that of the pseudomonad ATCases.
      Two of these ATCases come from bacteria outside the gamma-subgroup of the
      Proteobacteria, one from the alpha-subgroup and one from Deinococcus radiophilus,
      a species phylogenetically remote from the Proteobacteria. Unexpectedly, three
      bacterial species, closely related to the fluorescent pseudomonads and
      acinetobacters, have ATCases of 100 kDa (class C). One of these, Stenotrophomonas
      (formerly Xanthomonas) maltophilia has been purified and found to be a homotrimer
      of 35 kDa polypeptide chains. We believe this is the first time that class C
      ATCases have been reported in Gram-negative bacteria. A distinctive cluster in
      the gamma-3 subgroup of the Proteobacteria is formed by the enteric bacteria and
      their relatives. So far only class B ATCases have been reported in this group.
      The evolutionary implications of these findings are discussed.

PMID- 8757752
TI  - Evaluation of the DNA fingerprinting method AFLP as an new tool in bacterial
      taxonomy.
AB  - We investigated the usefulness of a novel DNA fingerprinting technique, AFLP,
      which is based on the selective amplification of genomic restriction fragments by
      PCR, to differentiate bacterial strains at the subgeneric level. In totals, 147
      bacterial strains were subjected to AFLP fingerprinting: 36 Xanthomonas strains,
      including 23 pathovars of Xanthomonas axonopodis and six pathovars of Xanthomonas
      vasicola, one strain of Stenotrophomonas, 90 genotypically characterized strains
      comprising all 14 hybridization groups currently described in the genus
      Aeromonas, and four strains of each of the genera Clostridium, Bacillus,
      Acinetobacter, Pseudomonas and Vibrio. Depending on the genus, total genomic DNA
      of each bacterium was digested with a particular combination of two restriction
      endonucleases and the resulting fragments were ligated to restriction halfsite
      specific adaptors. These adaptors served as primer-binding sites allowing the
      fragments to be amplified by selective PCR primers that extend beyond the adaptor
      and restriction site sequences. Following electrophoretic separation on 5% (w/v)
      polyacrylamide/8.3 M urea, amplified products could be visualized by
      autoradiography because one of the selective primers was radioactively labelled.
      The resulting banding patterns, containing approximately 30-50 visualized PCR
      products in the size range 80-550 bp, were captured by a high-resolution
      densitoscanner and further processed for computer-assisted analysis to determine
      band-based similarity coefficients. This study reveals extensive evidence for the
      applicability of AFLP in bacterial taxonomy through comparison of the newly
      obtained data with results previously obtained by well-established genotypic and
      chemotaxonomic methods such as DNA-DNA hybridization and cellular fatty acid
      analysis. In addition, this study clearly demonstrates the superior
      discriminative power of AFLP towards the differentiation of highly related
      bacterial strains that belong to the same species or even biovar (i.e. to
      characterize strains at the infrasubspecific level), highlighting the potential
      of this novel fingerprinting method in epidemiological and evolutionary studies.

PMID- 8757753
TI  - Intra-specific diversity and host specificity within Pasteurella haemolytica
      based on variation of capsular polysaccharide, lipopolysaccharide and outer
      membrane proteins.
AB  - Intra-specific diversity within Pasteurella haemolytica was assessed by analysing
      variation in the capsular polysaccharide (serotypes), lipopolysaccharide (LPS)
      and outer-membrane proteins (OMPs) of 184 isolates recovered from cattle and
      sheep. Four 12 serotypes comprised 83% of the total number of isolates, including
      A1 and A2 as the most frequently recovered serotypes from cattle and sheep,
      respectively. Nine distinct LPS profiles were identified. Four different core
      oligosaccharide patterns were present, each of which occurred alone as rough LPS
      and also in association with single O-antigen profile as smooth LPS; the ninth
      LPS type was also smooth but had a different O-antigen profile. The capsular
      serotypes could be divided into four groups based on the dominant LPS profile
      within each serotype: (1) A1, A6, A9, A12 and A5; (2) A2, A8, A14 and A16; (3) A7
      and A13; and (4) A11. Smooth LPS of type 1A, which was found only in the first
      group, was associated primarily with bovine disease isolates, whereas rough LPS
      of types 1B and 3B were associated primarily with group 2 serotypes and ovine
      disease isolates. Similarly, the variation of OMP profiles generated three
      groups: (1) A1, A6 A9, A12, A5 and A8; (2) A2, A14 and A16; and (3) A7, A11 and
      A13. Isolates belonging to groups 2 and 3 exhibited greater diversity in their
      OMP profiles than those belonging to group 1. Although the majority of group 3
      isolates possessed profiles unique to that group, a smaller number of A7 isolates
      possessed profiles with similarities to those of serotypes A1 or A2. OMP profiles
      clearly differentiated bovine from ovine isolates of the same serotypes. The
      association both of specific LPS and OMP profiles with bovine or ovine disease
      isolates suggested a correlation between specific cell-surface structures and
      host specificity. The combined analysis of capsular serotypes, LPS types and OMP
      profiles identified seven major groups within P. haemolytica which were
      responsible for 59% of the disease cases, suggesting a clonal structure for this
      species. Overall, comparison of the capsular serotypes, LPS types and OMP
      profiles proved extremely useful for assessing diversity within P. haemolytica.

PMID- 8757754
TI  - Stromelysin-3 mRNA associated with myofibroblasts is overexpressed in aggressive
      basal cell carcinoma and in dermatofibroma but not in dermatofibrosarcoma.
AB  - Stromelysin-3 is produced in the stroma of various malignant tumors, and in
      breast carcinoma there seems to be a positive correlation between aggressive
      disease and intensity of stromelysin-3 expression, suggesting that stromelysin-3
      participates in the tumor spread. In basal cell carcinoma, previous findings on
      stromelysin-3 have been inconclusive in this respect. Our study was undertaken to
      determine the pattern of stromelysin-3 production in relation to different
      histologic subtypes and stromal reactions in basal cell carcinoma. By in situ
      hybridization, stromelysin-3 mRNA was detected in stromal fibroblastic cells in
      51/56 samples. Furthermore, there was a significant correlation between strong
      signal for stromelysin-3 mRNA and infiltrative tumor growth. In all tumors, there
      was ongoing collagen synthesis as shown by a signal for procollagen I mRNA; this
      signal co-localized with stromelysin-3 around tumor nests. Our findings suggest a
      link between stromelysin-3 and fibrotic stromal response, which prompted us to
      evaluate the expression of stromelysin-3 in other fibrotic skin tumors.
      Interestingly, stromelysin-3, co-localizing with procollagen I mRNA, was
      consistently expressed in lesional cells in dermatofibromas (19/19), but not in
      dermatofibrosarcomas (0/7). Thus, our results indicate that in addition to being
      a marker for malignant disease, stromelysin-3 is produced by fibroblastic cells
      associated with benign fibrosis. A subset of cells producing stromelysin-3
      appears to be myofibroblasts as demonstrated by immunoreactivity for alpha smooth
      muscle actin in both basal cell carcinoma and dermatofibroma.

PMID- 8757755
TI  - Glutathione, glutathione S-transferase and reactive oxygen species of human scalp
      sebaceous glands in male pattern baldness.
AB  - We investigated the contribution of reactive oxygen species to the development of
      sebaceous gland hyperplasia and the characteristics of the glutathione S
      transferase/glutathione system in male pattern baldness. Glutathione S
      transferase, glutathione, and thiobarbituric acid-reactive substances were
      determined in sebaceous gland-enriched scalp skin of men affected by male pattern
      baldness and were subjected to hair autotransplantation. In comparison with the
      hairy occipital-donor areas, the following results were obtained in alopecic
      frontoparietal samples: glutathione S-transferase-specific activity increased 7
      fold (p < 0.001); enzyme affinity towards 1-chloro-2,4-dinitrobenzene decreased 2
      fold (p = 0.009); glutathione content decreased 2.5-fold (p = 0.017); and
      thiobarbituric acid reactive substances increased 2-fold (p = 0.006).
      Chromatofocusing analysis, bromosulfophthalein IC50 values, enzyme-linked
      immunosorbent assay, and immunohistochemistry with polyclonal antibodies raised
      against glutathione S-transferases alpha, mu, and pi demonstrated the presence of
      alpha, pi, and probably the 5.8 alpha isoenzymes in the sebaceous gland. These
      results support the hypothesis that reactive oxygen species are involved in the
      pathogenesis of sebaceous gland hyperplasia in male pattern baldness.

PMID- 8757756
TI  - Inhibition of neutrophil elastase suppresses the development of skin tumors in
      hairless mice.
AB  - In this study we investigated whether a reduction in neutrophil elastase activity
      in mice would alter the development of ultraviolet B or chemically induced skin
      tumors. A mutant strain of neutrophil elastase-deficient mice was developed by
      crossing beige mice with SKH 1 hairless mice. Ultraviolet irradiation three times
      per week for 20 wk developed an average of 10 tumors per normal mouse, whereas
      elastase-deficient hairless mice receiving the same treatment developed only 0.4
      tumors per mouse. Benzopyrene administered topically for 20 wk resulted in an
      average of seven tumors per control mouse, while similar treatment to elastase
      deficient hairless mice reduced the tumor count to 0.2 per mouse. Two small
      molecular weight elastase inhibitors, which were shown to inhibit mouse
      neutrophil elastase, were administered subcutaneously to normal SKH-1 mice during
      16 wk of ultraviolet B exposure. Both inhibitors significantly reduced the
      incidence of ultraviolet B-induced tumors. When control and elastase-deficient
      mice were immunized with 2,4,6-trinitrochlorobenzene and oxazolone, both
      molecules elicited a significant contact hypersensitivity response. Ultraviolet B
      irradiation prior to immunization at a nonirradiated site completely suppressed
      the induction of contact hypersensitivity in both the normal and the deficient
      mice, suggesting that prevention of systemic immunosuppression was not the reason
      for the resistance to skin tumors observed in the elastase-deficient mice. The
      results suggest that neutrophil elastase can be an important factor in squamous
      cell tumor development.

PMID- 8757758
TI  - Clinicopathological correlations of compound heterozygous COL7A1 mutations in
      recessive dystrophic epidermolysis bullosa.
AB  - Recessive dystrophic epidermolysis bullosa is an inherited mechano-bullous
      disorder of skin and mucous membranes. Ultrastructurally, the disease is
      characterized by abnormalities of anchoring fibrils, attachment structures below
      the epidermal basement membrane, composed of type VII collagen. Mutations in the
      type VII collagen gene (COL7A1) have been shown conclusively to underlie
      dystrophic epidermolysis bullosa. Since there is variation of the phenotype,
      accompanied by heterogeneous anchoring fibril morphology and type VII collagen
      immunostaining, it is conceivable that different types and combinations of COL7A1
      mutations correlate with different phenotypes. We therefore screened recessive
      dystrophic epidermolysis bullosa patients for COL7A1 mutations. Three unrelated
      patients showed the same premature termination codon mutation in exon 13 of one
      allele, yet they were all compound heterozygotes, each having a different
      mutation in the second allele. The first patient had a premature termination
      codon within the collagenous region of COL7A1 associated with severe disease,
      absent anchoring fibrils and undetectable type VII collagen immunostaining. The
      second had a premature termination codon in the non-collagenous NC-2 region
      associated with severe disease, wispy anchoring fibrils, and patchy type VII
      collagen immunostaining. The third had a glycine-to-aspartic acid substitution
      within the collagenous region, associated with milder disease, no identifiable
      anchoring fibrils, but near normal type VII collagen immunostaining. We conclude
      that the nature and position of mutations within COL7A1 correlate with specific
      disease features and may provide an insight into the molecular mechanisms of
      anchoring fibril formation and epidermal-dermal adhesion.

PMID- 8757757
TI  - Recombinant anti-human melanoma antibodies are versatile molecules.
AB  - The low cost, high versatility, and reliable production of bacterially produced
      recombinant antibody fragments speeds up the development of tumor-targeting
      agents. High-quality recombinant anti-melanoma antibodies are much sought after
      in the scientific community. We cloned the murine antibody 225.28S, currently
      used in radioimmunoimaging of human melanoma lesions, in single-chain Fv
      configuration (scFv) for soluble expression in bacteria. The recombinant antibody
      fragment conserved the binding specificity of the parental antibody. In order to
      arm the scFv(225.28S) with biologically useful effector functions, we developed
      vectors for soluble expression of scFv(225.28S) in bacteria that allow both
      covalent and noncovalent chemical antibody modification at positions that do not
      interfere with antigen binding. An expression vector was developed that appends a
      cysteine residue at the C-terminal extremity of the recombinant antibody, thus
      allowing reaction with thiol-specific reagents, including 99mTc labeling, at a
      position that does not interfere with antigen binding. The scFv(225.28S) was also
      successfully expressed with a casein kinase II substrate tag that enables
      efficient and stable 32P labeling. For noncovalent antibody modification, we
      developed an expression vector that appends the human calmodulin gene at the C
      terminal extremity of scFv(225.28S). The calmodulin domain is poorly immunogenic
      and can be targeted with chemically modified high-affinity calmodulin ligands.
      The recombinant anti-human melanoma antibodies described in this article should
      prove useful "building blocks" for the development of anti-melanoma diagnostic
      and therapeutic strategies.

PMID- 8757759
TI  - Extraction of human epidermis treated with retinol yields retro-retinoids in
      addition to free retinol and retinyl esters.
AB  - Vitamin A, all-trans-retinol, is metabolized to retinoic acid in vivo by a
      tightly controlled two-step conversion. Retinoic acid then binds to nuclear
      receptors and modulates cellular proliferation and differentiation. Because only
      a small fraction of retinol applied topically can be metabolized to retinoic
      acid, alternative pathways of retinol metabolism in skin were investigated.
      Retinol (0.4%) was applied to adult human skin under occlusion for 6 h to 4 d.
      The conversion of retinol into various metabolites such as 14-hydroxy-4,14-retro
      retinol, anhydroretinol, 4-oxo-retinol, retinyl esters, and retinyl glucuronides
      was investigated. The level of 14-hydroxy-retro-retinol was increased from
      undetectable at time 0 to 326 ng/g wet weight of tissue at 6 h (6% of the retinol
      level) and maintained approximately the same concentration at 24 h to 409 ng/g
      wet weight (1.9% of the retinol level); it decreased to 48 ng/g wet weight of
      tissue (12% of its maximum level) by 4 d. Anhydroretinol was undetectable at time
      0, increased only slightly at 6 h, and remained at the same level. We did not
      detect 4-oxo-retinol. Because 14-hydroxy-retro-retinol was found in the retinol
      treated areas, its effects on epidermis were compared with those of retinol.
      Topical application of trans-retinol (0.3%) significantly increased both
      epidermal thickness and cellular retinoic acid binding protein II mRNA, whereas
      14-hydroxy-4,14-retro-retinol (0.3%) did not increase either of these well
      characterized cutaneous retinoid responses. Retinol, when applied topically in
      pharmacologic doses to human epidermis, remained as free retinol, was metabolized
      primarily to retinol ester, and was metabolized to a lesser extent to retro
      retinoids and didehydroretinol.

PMID- 8757760
TI  - Liarozole inhibits human epidermal retinoic acid 4-hydroxylase activity and
      differentially augments human skin responses to retinoic acid and retinol in
      vivo.
AB  - Metabolic inactivation of all-trans retinoic acid to 4-hydroxy retinoic acid
      occurs via a cytochrome P-450 enzyme. We investigated the effects of liarozole on
      the retinoic acid 4-hydroxylase activity of human epidermis and its ability to
      modify in vivo human skin responses to retinoic acid and all-trans retinol.
      Retinoic acid 4-hydroxylase activity induced in vivo by 4 d treatment with
      retinoic acid (0.1%) was inhibited in vitro by liarozole in a concentration
      dependent manner. Comparable micromolar concentrations of liarozole were
      extracted from stratum corneum-free epidermis treated with 3% liarozole. Retinoic
      acid levels in liarozole-treated skin increased to 19 +/- 5 ng/g wet wt (mean +/-
      SEM, p < 0.002, n = 17) at 18 h and to 6 +/- 2 ng/g wet wt (p = 0.38, n = 17) at
      48 h as compared to vehicle (not detectable). At 48 h, retinoic acid 4
      hydroxylase activity was induced 9-fold over vehicle (p < 0.03, n = 8). At 96 h,
      no significant erythema or increased epidermal thickness was found when either
      retinoic acid (0.001%), all-trans retinol (0.0250%), or liarozole (3%) was
      applied individually, but when 0.001% retinoic acid and 3% liarozole were applied
      together, both erythema and increased epidermal thickness occurred. In contrast,
      0.025% all-trans retinol and 3% liarozole together caused increased epidermal
      thickness but no erythema. These data demonstrate that, at doses used here,
      liarozole, although an effective inhibitor of retinoic acid 4-hydroxylase, cannot
      function alone like a retinoid in vivo, probably because of retinoic acid 4
      hydroxylase induction. In the presence of a low dose retinoic acid or all-trans
      retinol, however, liarozole can amplify human skin responses to each retinoid in
      a manner characteristic of the retinoid at a higher dose (erythema and
      hyperplasia with retinoic acid; no erythema but hyperplasia with all-trans
      retinol).

PMID- 8757761
TI  - Thapsigargin induces rapid, transient growth inhibition and c-fos expression
      followed by sustained growth stimulation in mouse keratinocyte cultures.
AB  - Although the sesquiterpene lactone thapsigargin has been shown to possess
      hyperplastic and tumor-promoting activities when applied topically to mouse skin
      in vivo, the cellular mechanism(s) which underlie these effects are unclear. We
      show here that thapsigargin treatment of Primary mouse epidermal keratinocytes
      increased intracellular free Ca2+ concentration (Cai) in a concentration
      dependent manner. Thapsigargin induced a rapid, transient elevation in
      keratinocyte Cai, in part due to the release of Ca2+ from intracellular stores.
      This response was followed by a sustained elevation in Ca2+, resulting entirely
      from calcium influx. Thapsigargin elicited a biphasic effect on keratinocyte DNA
      synthesis: a rapid inhibitory effect (50-60% inhibition at 4-8 h), followed by a
      very marked and sustained elevation. Prolonged treatment of keratinocytes with
      thapsigargin at relatively high concentrations resulted in cytotoxicity
      (inhibition of neutral red uptake). The rapid antiproliferative effect of
      thapsigargin was not associated with cytotoxicity, as determined by either
      neutral red uptake or by trypan blue exclusion, and was not blocked by
      pretreatment with Ro 31-7349, a selective inhibitor of protein kinase C. The
      rapid antiproliferative effect of thapsigargin was associated with rapid,
      transient activation of keratinocyte c-fos expression and rapid inhibition of
      total protein synthesis. Taken together, these findings raise the possibility
      that the hyperplastic and tumor-promoting activities of thapsigargin on epidermis
      in vivo result from direct keratinocyte growth stimulation as a consequence of a
      prolonged elevation in levels of Cai.

PMID- 8757762
TI  - Ligand activation of overexpressed epidermal growth factor receptor results in
      loss of epithelial phenotype and impaired RGD-sensitive integrin function in HSC
      1 cells.
AB  - Various human carcinomas overexpress epidermal growth factor receptor, and the
      degree of the expression correlates with their malignant phenotype. Because
      phenotypic transformation of cells involves qualitative and quantitative
      alteration of integrin function, we compared the effects of exogenous epidermal
      growth factor on cell-matrix interactions between HSC-1 human cutaneous squamous
      carcinoma cells overexpressing epidermal growth factor receptor and their
      revertant cells. Epidermal growth factor impaired RGD-sensitive cell spreading on
      fibrinogen, fibronectin, or vitronectin in the parent cells in a concentration
      dependent manner; 50 ng epidermal growth factor per ml treatment for 1-24 h
      reduced cell spreading on these substrata by 75-95%. In the presence of epidermal
      growth factor, the parent HSC-1 cells lost their epithelial phenotype and did not
      form coherent colonies. This might involve the impaired RGD-sensitive integrin
      function, because treatment of the cells with the peptide GRGDS mimicked the
      effects of epidermal growth factor on cell and colony morphology. The revertant
      cells expressing about one-tenth the amount of epidermal growth factor receptor
      did not show reduced RGD-sensitive cell spreading or loss of epithelial phenotype
      in response to epidermal growth factor. Epidermal growth factor did not
      downregulate the subunits for the RGD-sensitive integrin receptors for
      fibrinogen, fibronectin, or vitronectin. Tyrosine phosphorylation of integrin
      beta subunits might be involved in the impairment of integrin function, because
      EGF tyrosine phosphorylated beta1, subunit in the parent, but not in the
      revertant cells. Our results suggest that the ligand activation of overexpressed
      epidermal growth factor receptor results in impairment of RGD-sensitive integrin
      function and loss of epithelial phenotype. This may be advantageous to epithelial
      tumor cells progressing along malignant pathways.

PMID- 8757763
TI  - Immunoglobulin E response to human proteins in atopic patients.
AB  - The demonstration that human IgE recognizes both exogenous allergens and
      structurally related human proteins has led to the hypothesis that IgE
      autoreactivity may be a pathogenic factor in atopic diseases. To determine the
      frequency of occurrence as well as the disease specificity of this phenomenon, we
      tested sera from patients with atopic diseases and, for control purposes, from
      persons with immunologically mediated disorders for serum IgE reactivity with
      nitrocellulose-blotted human proteins. We found that 12 of 20 sera from atopic
      patients with pronounced skin lesions contained Western blot-detectable IgE
      antibodies. Patients suffering predominantly from allergic rhinoconjunctivitis as
      well as control individuals failed to display serum IgE autoreactivity, but
      occasionally exhibited elevated serum IgE levels. The molecular weights of the
      IgE-defined autoantigens ranged predominantly from 10 to 100 kDa. Whereas some of
      these were expressed in only certain cell types, others were detected in
      histogenetically different cells. Our results suggest that IgE autoimmunity
      occurs frequently in atopic dermatitis patients and may be of pathogenic
      relevance for the chronicity of skin manifestations typical of this disease.

PMID- 8757764
TI  - The 105-kDa basement membrane autoantigen p105 is N-terminally homologous to a
      tumor-associated antigen.
AB  - Certain constitutive skin basement membrane components, such as bullous
      pemphigoid antigens and epidermolysis bullosa acquisita antigen, were discovered
      because they were targeted by an autoimmune reaction. We aimed to purify and
      characterize a 105-kDa skin basement membrane protein termed p105 recognized by
      autoantibodies (anti-p105) from patients with a unique immune-mediated
      subepidermal blistering skin disease. A simian virus 40-transformed human
      fibroblast cell line that synthesizes and secretes p105 was utilized as the
      protein source. p105 was partially purified by salt-gradient fractionation of
      serum-free conditioned medium through a Mono Q anion-exchange column and by
      examining each fraction with protein staining and immunoblotting against anti
      p105. p105 was isolated from polyacrylamide gel electrophoresis gels, blotted
      onto polyvinylidene difluoride membrane, and subjected to protein
      microsequencing. The 20 microsequenced N-terminal amino acids exhibited no
      homology to known basement membrane proteins but exhibited a 70% homology to a 90
      kDa tumor-associated antigen. Antibodies raised against a peptide generated from
      these amino acid sequences reacted to a 105-kDa western-blotted keratinocyte and
      fibroblast protein and a basement membrane component. p105 resisted digestion by
      glycosidases chondroitinase ABC, neuraminidase, and N-glycosidase F but was
      cleaved by protease V8 to antigenic fragments of 22 kDa and 14 kDa. The synthesis
      of p105 was inhibited by cycloheximide. We conclude that p105 is a unique
      basement membrane component produced by both keratinocytes and fibroblasts.

PMID- 8757765
TI  - RET mutation screening in familial cutaneous lichen amyloidosis and in skin
      amyloidosis associated with multiple endocrine neoplasia.
AB  - In several families, multiple endocrine neoplasia type 2A (MEN 2A) has been found
      in association with cutaneous lichen amyloidosis. It has been debated, however,
      whether the skin amyloidosis found in MEN 2A families, localized exclusively in
      the interscapular area, represents the same anomaly as that found in autosomal
      dominant familial cutaneous lichen amyloidosis, which is more generalized. We
      screened two MEN 2A families with associated skin amyloidosis for germline
      mutations in the RET gene responsible for the MEN 2A cancer syndrome, and found
      the same mutation characteristic of MEN 2A in both families. We also screened
      probands from three pedigrees with familial cutaneous lichen amyloidosis for RET
      mutations. In none of the RET coding and flanking intronic sequences was a
      mutation detected. This most probably indicates that skin amyloidosis found in
      some MEN 2A families and familial cutaneous lichen amyloidosis are different
      conditions. Consequently, patients with apparent familial cutaneous lichen
      amyloidosis do not appear to be at risk for MEN 2A.

PMID- 8757766
TI  - Release of stem cell factor from a human keratinocyte line, HaCaT, is increased
      in differentiating versus proliferating cells.
AB  - Stem cell factor, a recently discovered growth factor for hematopoietic stem
      cells, mast cells, and melanocytes, was initially reported to be produced by
      fibroblasts. In this study, we investigated the secretion of this factor from
      human HaCaT cells during in vitro culture and compared it to synthesis by cells
      in the skin. Release of stem cell factor from freshly cultured keratinocytes was
      comparable to that of HaCaT cells and was nearly half that produced by
      fibroblasts and umbilical vein endothelial cells. No stem cell factor was
      detectable in culture supernatants of melanocytes. HaCaT cells underwent
      spontaneous differentiation after a period of proliferation until confluency.
      Depending on duration of culture, they released increasing amounts of stem cell
      factor (approximately 150 pg/10(6) cells on day 3 (proliferating cells) vs
      approximately 450 pg/10(6) cells on day 14 (differentiating cells) measured by
      enzyme-linked immunosorbent assay. Stimulation for 24 h with the calcium
      ionophore A 23187 (10(-6) to 10(-8) M) further enhanced release. Western blot
      analysis of HaCaT cell lysates with a stem cell factor antibody revealed two
      proteins with the known molecular weights of membrane-bound and soluble stem cell
      factor. By semiquantitative reverse transcriptase polymerase chain reaction, full
      length as well as spliced type stem cell factor mRNA was found to be increased in
      differentiating versus proliferating HaCaT cells. Keratinocytes are thus
      potentially important sources of stem cell factor in human skin, and HaCaT cells
      provide a useful model for further studies of stem cell factor from
      keratinocytes.

PMID- 8757768
TI  - In the absence of streptomycin, minoxidil potentiates the mitogenic effects of
      fetal calf serum, insulin-like growth factor 1, and platelet-derived growth
      factor on NIH 3T3 fibroblasts in a K+ channel-dependent fashion.
AB  - There is considerable evidence to suggest that the opening of K+ channels plays
      an important role in stimulating mitogenesis. K+ channel blockers have been shown
      to inhibit mitogenesis in vitro, mitogens increase cytosolic membrane K+ channel
      permeability, K+ channel openers stimulate hair growth in vivo, and the Ras/Raf
      signal transduction pathway induces K+ channel activity. Paradoxically, however,
      K+ channel openers such as minoxidil have been reported in vitro not to modulate,
      or even to inhibit, mitogenesis in a range of cell types. Only untherapeutic
      concentrations have stimulated mitogenesis. These experiments, however, appear to
      have been carried out in the presence of aminoglycoside antibiotics, which
      inhibit potassium channel activity. We now report that in the absence of
      aminoglycoside antibiotics, minoxidil at 10 microg/ml (0.05 mM) causes a
      significant stimulation of proliferation of NIH 3T3 fibroblasts maintained over a
      10-d period in 5% fetal calf serum-supplemented medium. Further, we show that in
      the presence of 100 microg streptomycin per ml, minoxidil at 10 microg/ml
      produces an initial inhibition of proliferation, which apparently confirms, in
      NIH 3T3 fibroblasts, that the inhibition of mitogenesis by minoxidil in the
      presence of streptomycin is an artifact. The potentiation of NIH 3T3 cell growth
      by minoxidil can be attributed to the opening of potassium channels, because the
      potassium channel blocker tolbutamide (5 mM) or combinations of the blockers
      tolbutamide (1 mM)/tetraethylammonium (2 mM) or glibenclamide (1 microM)/apamin
      (10 nM) block the minoxidil-induced stimulation of growth. We also demonstrate
      that minoxidil is able to significantly potentiate the mitogenic effects of both
      platelet-derived growth factor and insulin-like growth factor 1 on NIH 3T3
      fibroblasts in the presence of CPSR-2 (a cytokine free serum substitute). Thus we
      have shown that minoxidil potentiates the mitogenic effects of fetal calf serum
      in vitro on NIH 3T3 fibroblasts by opening potassium channels and is also able to
      potentiate the mitogenic effects of the growth factors platelet-derived growth
      factor and insulin-like growth factor 1.

PMID- 8757767
TI  - The recognition of human 60-kDa Ro ribonucleoprotein particles by antibodies
      associated with cutaneous lupus and neonatal lupus.
AB  - The hY RNAs form a macromolecular complex with the 60-kDa Ro protein and may in
      addition be bound by the La protein. In this study, we examine the autoantibody
      responses to the intact protein-RNA complexes in 18 subacute cutaneous lupus
      (SCLE), 10 discoid lupus (DLE), and 18 neonatal lupus erythematosus (NLE) sera.
      All SCLE and NLE serum samples precipitated all four of the Ro hY RNAs, whereas
      none of the DLE serum samples precipitated the hY RNAs. Among the SCLE and NLE
      sera, there was a significant association between the amount of Ro hY RNAs
      precipitated and the concurrent presence of anti-La antibodies in the sera (p =
      0.008), consistent with the hypothesis that both the 60-kDa Ro and the La
      proteins can bind the Ro hY RNAs. There was no correlation between the amount of
      hY RNAs precipitated and the titer of antibodies to the 60-kDa Ro protein in
      enzyme-linked immunosorbent assay (ELISA). This may be due to a difference in the
      epitopes formed by the antigen in the respective assays. The autoantibody
      response to Ro in SCLE and NLE, which is generally detectable by both
      immunodiffusion and ELISA, is directed to all the subsets of the Ro protein-hY
      RNA complexes. The autoantibody response in DLE, though frequently detectable by
      ELISA, is not of sufficient concentration or affinity to precipitate the Ro
      protein-RNA complexes. The autoantibody response to Ro in SCLE and NLE may
      include antibodies to epitopes created by the complexing of the 60-kDa Ro protein
      with hY RNA.

PMID- 8757769
TI  - Apoptosis induction of ultraviolet light A and photochemotherapy in cutaneous T
      cell Lymphoma: relevance to mechanism of therapeutic action.
AB  - The anti-tumor action of many chemotherapeutic agents has recently been
      attributed to the induction of apoptosis in the malignant cell population. In
      this study, we investigated the ability of extracorporeal photopheresis (ExP) and
      in vitro PUVA (8-methoxy-psoralen + ultraviolet A) therapy to induce apoptosis in
      peripheral blood mononuclear cells from Sezary syndrome patients and normal
      controls. Flow cytometric analysis of ExP- or PUVA-treated peripheral blood
      lymphocytes demonstrated two distinct cell populations within 24 h of treatment.
      One population was similar to untreated controls with the other exhibiting
      characteristics of apoptotic cell death, i.e., a loss of cell volume and an
      accompanying increase in cell density. This latter population was comprised of
      cells with DNA strand breaks as determined by the Tdt-mediated deoxyuridine
      triphosphate-biotin nick end labeling assay. Apoptosis was also confirmed
      morphologically by fluorescent and electron microscopy as well as by
      demonstration of characteristic DNA strand breaks (laddering) using gel
      electrophoresis. Apoptosis was not observed with 8-methoxypsoralen (< or = 300 ng
      per ml) alone; however, ultraviolet A alone at doses > or = 2 J per cm2 induced
      apoptosis in lymphocytes. Peripheral blood T-cell subpopulations of Sezary
      syndrome patients, including the malignant clone, were equally susceptible to
      apoptosis subsequent to either photopheresis or PUVA treatment. In contrast,
      monocytes (CD14+/CD45+) appear to be resistant to apoptosis induction by ExP or
      PUVA treatment. Moreover, ExP-treated and untreated monocytes phagocytized
      apoptotic, but not untreated, peripheral blood mononuclear cells. ExP and PUVA
      have been shown to be efficacious and well-tolerated therapies in the treatment
      of dermatologic diseases and transplant rejection. These data suggest that
      induction of apoptosis may be an important event for therapeutic efficacy.

PMID- 8757770
TI  - Induction of low zone tolerance to contact allergens in mice does not require
      functional Langerhans cells.
AB  - Epidermal Langerhans cells are known to be the major controlling element in the
      development of contact hypersensitivity. Haptenic molecules permeating the skin
      are taken up locally by Langerhans cells and then presented to T lymphocytes in
      the regional lymph nodes. Despite the presence of functional Langerhans cells,
      however, subsensitizing doses of hapten applied epicutaneously induce tolerance.
      We examined epidermal Langerhans cells at the site of contact with picryl
      chloride or oxazolone in BALB/c and C57B1/6 mice with regard to their responding
      to either subsensitizing or sensitizing doses of allergen. Subsensitizing doses
      did not interfere with the membranous adenosine triphosphatase system on
      Langerhans cells, known to relate to functional readiness of the cell.
      Accordingly, on electron microscopy the ultrastructure of Langerhans cells was
      found to be like that in untreated skin. In contrast, sensitizing doses caused a
      significant depletion of adenosine triphosphatase-positive Langerhans cells, and
      electron microscopy revealed marked cellular activation of Langerhans cells, with
      enlarged nuclei and increased numbers of mitochondria and Birbeck granules.
      Furthermore, subsensitizing doses induced tolerance regardless of whether
      Langerhans cells were functionally intact or had their function blocked
      arbitrarily. Blocking was achieved either by preceding ultraviolet B irradiation
      at the site of application or by painting of a sensitizer before painting another
      sensitizer on the same site. Moreover, not even surgical removal of the site
      within minutes after painting could prevent the induction of tolerance. The data
      suggest that subsensitizing doses of contact allergens painted on normal murine
      skin bypass involvement of epidermal Langerhans cells.

PMID- 8757771
TI  - Differential activation of protein kinase C isozymes by phorbol ester and
      collagen in human skin microvascular endothelial cells.
AB  - Human dermal microvascular endothelial cells participate in activities including
      inflammation, wound healing, and angiogenesis (neovascularization). Two stages of
      angiogenesis can be mimicked in vitro by two models of cultured foreskin human
      dermal microvascular endothelial cells: the differentiation of epithelioid
      endothelial cells to spindle-shaped mesenchymal-like cells induced by phorbol
      ester treatment; and the formation of vascular channels induced by exposing the
      luminal surface of endothelial cell monolayers to type I collagen gels. The
      mechanisms underlying these two processes, however, are largely unknown. Protein
      kinase C isozymes, which are activated by phorbol esters, are important mediators
      in the angiogenic process. In the current work, we identified the protein kinase
      C isozymes present in human dermal microvascular endothelial cells and determined
      which of the isozymes are activated in response to phorbol ester or to collagen
      treatments. Using western blot analysis, we found that microvascular endothelial
      cells contain at least six protein kinase C isozymes (alpha, beta, delta,
      epsilon, zeta, eta). Immunocytochemical studies demonstrated that the isozymes
      are located in distinct cellular compartments and that following treatment with
      phorbol 12-myristate 13-acetate or with a collagen gel overlay, most isozymes
      (protein kinase C alpha, beta1, betaII, delta, epsilon, eta) translocated to
      different parts of the cell. Moreover, for two of these isozymes (betaII and
      eta), the localization differs after phorbol 12-myristate 13-acetate treatment as
      compared with collagen treatment. These results demonstrate that agents that
      mimic two stages in the angiogenic process in vitro initiate diverse changes in
      the subcellular localization of specific protein kinase C isozymes and suggest a
      role for different isozymes in this process.

PMID- 8757772
TI  - A novel keratin K5 gene mutation in Dowling-Meara epidermolysis bullosa simplex.
AB  - We examined keratin K14 and K5 genes mutation in a Japanese Dowling-Meara
      epidermolysis bullosa simplex patient with severe generalized blistering and
      erosions at birth. The patient had a C to T transition at the first position of
      codon 174 in the keratin K5 gene, which resulted in a Leu->Phe substitution at
      the highly conserved 1A domain in keratin K5. Thus, our results revealed a novel
      mutation in the helix initiation peptide of keratin K5.

PMID- 8757774
TI  - Eldercare.

PMID- 8757773
TI  - Increased oligonucleotide permeability in keratinocytes of artificial skin
      correlates with differentiation and altered membrane function.
AB  - We tested the permeability of fluorescent oligonucleotides in cultured human
      epidermal keratinocyte monolayers and keratinocytes grown in a 3-dimensional skin
      model. Oligonucleotide permeability in living cells was determined by confocal
      microscopy after either simple addition to the culture medium or topical
      application via oligonucleotide-saturated filters placed atop the artificial
      skin. In cultured monolayers, few keratinocytes (9%) were found to acquire
      intracellular oligonucleotides that were primarily localized to the nucleus. In
      contrast, keratinocytes grown in an artificial, 3-dimensional skin matrix
      acquired extensive oligonucleotide permeability as differentiation progressed.
      About 95% of the granular cells showed nuclear accumulation of oligonucleotides.
      About 70% of the oligonucleotide-permeable granular cells were viable as verified
      by a mitochondria-specific, potential-sensitive dye, tetramethyl rhodamine ethyl
      ester. A marker used to study apoptotic cells with altered membrane potential,
      merocyanine 540, was found elevated in the cytoplasm of granular cells. In
      contrast, cultured keratinocyte monolayers or basal keratinocytes of skin showed
      a membrane staining pattern typical of undifferentiated cells. Few cells (<3%) of
      the basal layer had nuclear oligonucleotides, but none of the labeled cells were
      viable. These results suggest that the development of oligonucleotide and
      merocyanine 540 permeability in differentiated granular cells parallels the
      changes in membrane permeability found in other apoptotic systems.

PMID- 8757775
TI  - Safety first--mostly.

PMID- 8757776
TI  - Telemedicine: physicians using latest technology to help patients.

PMID- 8757777
TI  - Heri, Hodie, Cras ... yesterday, today, and tomorrow.

PMID- 8757778
TI  - Who/where is my doctor?

PMID- 8757779
TI  - Cat scratch disease presenting as multifocal osteitis.

PMID- 8757780
TI  - Care of the geriatric trauma patient.

PMID- 8757781
TI  - A potentially fatal drug reaction.

PMID- 8757782
TI  - Avoiding problems prescribing to older patients.

PMID- 8757783
TI  - Tobacco use: Tennessee youths at risk.

PMID- 8757784
TI  - Cellular functions of immunophilins.
AB  - Immunophilins are members of a highly conserved family of proteins all of which
      are cis-trans peptidyl-prolyl isomerases. The prototypic members of the
      immunophilin family, cyclophilin A and FKPB12, were discovered on the basis of
      their ability to bind and mediate the immunosuppressive effects of the drugs
      cyclosporin, FK506, and rapamycin. However, the prolyl isomerase activity of
      these proteins is not involved in any of the immunosuppressive effects. Indeed,
      despite the fact that all members of the family are prolyl isomerases, the
      cellular role of this enzymatic function has not been clearly defined. In many
      cases, immunophilins are widely expressed and are present at high levels in some
      tissues. Moreover, while the number of proteins that belong to the immunophilin
      family continues to grow, the natural cellular functions of all but a few remain
      obscure. An example where immunophilins do appear to have a defined cellular
      role, in the absence of immunosuppressive ligands, is the modulation of
      intracellular calcium release channel function by FKBP12 and FKBP12.6. In this
      case, FKBPs are integral parts of three types of calcium release channel
      complexes, skeletal and cardiac ryanodine receptors and the inositol 1,4,5
      trisphosphate receptor. In each case, FKBPs modulate channel function possibly by
      enhancing the cooperativity between subunits.

PMID- 8757785
TI  - Regulation of protein transport to the nucleus: central role of phosphorylation.
AB  - Nuclear protein transport is integral to eukaryotic cell processes such as
      differentiation, transformation, and the control of gene expression. Although the
      targeting role of nuclear localization signals (NLSs) has been known for some
      time, more recent results indicate that NLS-dependent nuclear protein import is
      precisely regulated. Phosphorylation appears to be the main mechanism controlling
      the nuclear transport of a number of proteins, including transcription factors
      such as NFkappaB, c-rel, dorsal, and SWI5 from yeast. Cytoplasmic retention
      factors, intra- and intermolecular NLS masking, and NLS masking by
      phosphorylation are some of the mechanisms by which phosphorylation specifically
      regulates nuclear transport. Even nuclear localization of the archetypal NLS
      containing simian virus 40 large tumor antigen (T-ag) is regulated, namely by the
      "CcN motif," which comprises the T-ag NLS ("N") determining ultimate subcellular
      destination, a casein kinase II site ("C") 13 amino acids NH2-terminal to the NLS
      modulating the rate of nuclear import, and a cyclin-dependent kinase site ("c")
      adjacent to the NLS regulating the maximal level of nuclear accumulation. The CcN
      motif appears to be a special form of phosphorylation-regulated NLS (prNLS),
      where phosphorylation at site(s) close to the NLS specifically regulates NLS
      function. The regulation of nuclear transport through phosphorylation and prNLSs
      appears to be common in eukaryotic cells from yeast and plants to higher mammals.

PMID- 8757786
TI  - Principles of rhythmic motor pattern generation.
AB  - Rhythmic movements are produced by central pattern-generating networks whose
      output is shaped by sensory and neuromodulatory inputs to allow the animal to
      adapt its movements to changing needs. This review discusses cellular, circuit,
      and computational analyses of the mechanisms underlying the generation of
      rhythmic movements in both invertebrate and vertebrate nervous systems. Attention
      is paid to exploring the mechanisms by which synaptic and cellular processes
      interact to play specific roles in shaping motor patterns and, consequently,
      movement.

PMID- 8757787
TI  - Taste reception.
AB  - Recent research on cellular mechanisms of peripheral taste has defined
      transduction pathways involving membrane receptors, G proteins, second
      messengers, and ion channels. Receptors for organic tastants received much
      attention, because they provide the specificity of a response. Their future
      cloning will constitute a major advance. Taste transduction typically utilizes
      two or more pathways in parallel. For instance, sweet-sensitive taste cells of
      the rat appear to respond to sucrose with activation of adenylyl cyclase,
      followed by adenosine 3',5'-cyclic monophosphate (cAMP)-dependent membrane events
      and Ca2+ uptake. The same cells respond differently to some artificial
      sweeteners, i.e., with activation of phospholipase C (PLC) followed by inositol
      1,4,5-trisphosphate (IP3)-dependent Ca2+ release from intracellular stores. Some
      bitter tastants block K+ channels or initiate the cascade receptor G1 protein,
      PLC, IP3, and Ca2+ release or the cascade receptor alpha-gustducin,
      phosphodiesterase (PDE), cAMP decrease, and opening of cAMP-blocked channels.
      Membrane-permeant bitter tastants may elicit a cellular response by interacting
      with G protein, PLC, or PDE of the above cascades. Salt taste is initiated by
      current flowing into the taste cell through cation channels located in the apical
      membrane, even though basolateral channels may also contribute (following salt
      diffusion through paracellular pathways). In rodents, the Na+-specific component
      of salt taste is typically mediated by apical amiloride-sensitive Na+ channels,
      but less specific and not amiloride-sensitive taste components exist in addition.
      Sour taste may in part be mediated by amiloride-sensitive Na+ channels conducting
      protons, but other mechanisms certainly contribute. Thus the transduction of
      taste cells generally comprises parallel pathways. Furthermore, the transduction
      pathways vary with the location of taste buds on the tongue and, of course,
      across species of animals. To identify these pathways, to understand how they are
      controlled and why they evolved to this complexity are major goals of present
      research.

PMID- 8757788
TI  - Gastric endocrine cells: gene expression, processing, and targeting of active
      products.
AB  - Endocrine cells of the gastric epithelium secrete biologically active peptides
      and small messenger molecules such as histamine, serotonin, and gamma
      aminobutyric acid. The secretory products may act locally (paracrine or autocrine
      effects) or at distant targets after delivery in the circulation (hormonal
      effects). the contents of the gastric lumen control both secretion of gastric
      endocrine cells and the expression of genes involved in the synthesis of their
      active secretory products; in some cases, gene regulation may occur over periods
      as short as that required for digestion of a single meal. The conversion of
      inactive peptide precursors to their active forms takes place during transit
      along the secretory pathway and is only completed after sequestration in
      secretory granules. the processing of the gastrin precursor provides a useful
      model for studying prohormone processing. Generation of the well-known amidated
      gastrins requires prohormone cleavage and COOH-terminal amidation; the products
      stimulate acid secretion and mucosal growth. However, recent work indicates that
      biosynthetic intermediates that do not stimulate acid secretion may nevertheless
      act at a novel receptor to stimulate growth, so that control of prohormone
      processing determines which of two alternative types of biologically active
      peptide is released by gastrin cells. Gastric endocrine cells also have the
      capacity to accumulate small messenger molecules in secretory vesicles, via
      proton exchangers. Recent work indicates physiological regulation of the
      expression of genes encoding cytosolic enzymes such as histidine decarboxylase,
      which converts histidine to histamine, and of secretory granule transporters such
      as vesicular monoamine transporter type 2, which concentrates amines in secretory
      vesicles. Together these findings suggest that modulation of regulatory peptide
      and amine biosynthesis in gastric endocrine cells constitutes a primary response
      of the stomach to the arrival of a meal.

PMID- 8757789
TI  - Nuclear magnetic resonance spectroscopy of living systems: applications in
      comparative physiology.
AB  - The most attractive feature of nuclear magnetic resonance spectroscopy (MRS) is
      the noninvasive and nondestructive measurement of chemical compounds in intact
      tissues. MRS already has many applications in comparative physiology, usually
      based on observation of 31P, since levels of phosphorus compounds indicate tissue
      energy status and are changed during exercise, fatigue, recovery, hypometabolism,
      anesthesia, hypoxia, hypercapnia, and osmotic and acid stress. Nuclei other than
      31P may also be monitored, such as 1H, 13C, 15N, 19F, or 23Na, and applied in
      biological research. Particularly, 13C-MRS is interesting because it allows the
      analysis of metabolic pathways in living systems. Applications of MRS in
      comparative physiology and biochemistry are comprehensively discussed in this
      review. The main focus is on anaerobic metabolism during hypoxia, ischemia, and
      exercise. Species as widely different as slime molds, nematodes, frogs, turtles,
      and ducks have been studied by 31P-MRS. It is not surprising that striking
      species differences do occur, but many similarities are also observed. Unique is
      the occurrence of six different phosphagens with different values of Gibbs free
      energy in polychete worms The presence of a particular phosphagen may be related
      to the average oxygen tension within the tissues. Phosphagens and their kinases
      are also discussed in relation to hypercapnia and acid stress. Other topics
      discussed in this paper are enzyme kinetics, anesthetics, development and growth,
      parasitism, and the detection of previously unknown compounds.

PMID- 8757790
TI  - Oxygen sensing and molecular adaptation to hypoxia.
AB  - This review focuses on the molecular stratagems utilized by bacteria, yeast, and
      mammals in their adaptation to hypoxia. Among this broad range of organisms,
      changes in oxygen tension appear to be sensed by heme proteins, with subsequent
      transfer of electrons along a signal transduction pathway which may depend on
      reactive oxygen species. These heme-based sensors are generally two-domain
      proteins. Some are hemokinases, while others are flavohemoproteins
      [flavohemoglobins and NAD(P)H oxidases]. Hypoxia-dependent kinase activation of
      transcription factors in nitrogen-fixing bacteria bears a striking analogy to the
      phosphorylation of hypoxia inducible factor-1 (HIF-1) in mammalian cells.
      Moreover, redox chemistry appears to play a critical role both in the trans
      activation of oxygen-responsive genes in unicellular organisms as well as in the
      activation of HIF-1. In yeast and bacteria, regulatory operons coordinate
      expression of genes responsible for adaptive responses to hypoxia and hyperoxia.
      Similarly, in mammals, combinatorial interactions of HIF-1 with other identified
      transcription factors are required for the hypoxic induction of physiologically
      important genes.

PMID- 8757791
TI  - Structure and function of voltage-dependent sodium channels: comparison of brain
      II and cardiac isoforms.
AB  - Cardiac and nerve Na channels have broadly similar functional properties and
      amino acid sequences, but they demonstrate specific differences in gating,
      permeation, ionic block, modulation, and pharmacology. Resolution of three
      dimensional structures of Na channels is unlikely in the near future, but a
      number of amino acid sequences from a variety of species and isoforms are known
      so that channel differences can be exploited to gain insight into the
      relationship of structure to function. The combination of molecular biology to
      create chimeras and channels with point mutations and high-resolution
      electrophysiological techniques to study function encourage the idea that
      predictions of structure from function are possible. With the goal of
      understanding the special properties of the cardiac Na channel, this review
      examines the structural (sequence) similarities between the cardiac and nerve
      channels and considers what is known about the relationship of structure to
      function for voltage-dependent Na channels in general and for the cardiac Na
      channels in particular.

PMID- 8757792
TI  - Over-production of proteins in Escherichia coli: mutant hosts that allow
      synthesis of some membrane proteins and globular proteins at high levels.
AB  - We have investigated the over-production of seven membrane proteins in an
      Escherichia coli-bacteriophage T7 RNA polymerase expression system. In all seven
      cases, when expression of the target membrane protein was induced, most of the
      BL21(DE3) host cells died. Similar effects were also observed with expression
      vectors for ten globular proteins. Therefore, protein over-production in this
      expression system is either limited or prevented by bacterial cell death. From
      the few survivors of BL21(DE3) expressing the oxoglutarate-malate carrier protein
      from mitochondrial membranes, a mutant host C41(DE3) was selected that grew to
      high saturation cell density, and produced the protein as inclusion bodies at an
      elevated level without toxic effect. Some proteins that were expressed poorly in
      BL21(DE3), and others where the toxicity of the expression plasmids prevented
      transformation into this host, were also over-produced successfully in C41(DE3).
      The examples include globular proteins as well as membrane proteins, and
      therefore, strain C41(DE3) is generally superior to BL21(DE3) as a host for
      protein over-expression. However, the toxicity of over-expression of some of the
      membrane proteins persisted partially in strain C41(DE3). Therefore, a double
      mutant host C43(DE3) was selected from C41(DE3) cells containing the expression
      plasmid for subunit b of bacterial F-ATPase. In strain C43(DE3), both subunits b
      and c of the F-ATPase, an alanine-H(+) symporter, and the ADP/ATP and the
      phosphate carriers from mitochondria were all over-produced. The transcription of
      the gene for the OGCP and subunit b was lower in C41(DE3) and C43(DE3),
      respectively, than in BL21(DE3). In C43(DE3), the onset of transcription of the
      gene for subunit b was delayed after induction, and the over-produced protein was
      incorporated into the membrane. The procedure used for selection of C41(DE3) and
      C43(DE3) could be employed to tailor expression hosts in order to overcome other
      toxic effects associated with over-expression.

PMID- 8757793
TI  - Site-specific recombination by Tn3 resolvase, photocrosslinked to its supercoiled
      DNA substrate.
AB  - Site-specific recombination, transposition, and retroviral integration reactions
      involve the collaborative action of multiple identical protein subunits, making
      it difficult to determine the catalytic functions and fate of a subunit at any
      particular DNA binding site of the substrate. To investigate the mechanism of
      catalysis by the site-specific recombinase Tn3 resolvase, we fixed specific
      subunits to their binding sites by laser photocrosslinking, using a partially
      synthetic supercoiled DNA substrate containing photoreactive nucleotides.
      Crosslinked resolvase subunits were able to participate in a complete
      recombination reaction, demonstrating that the interaction of the subunit with
      its binding site persists throughout the reaction, and thus placing limitations
      on acceptable models for the catalytic mechanism.

PMID- 8757794
TI  - RNP export is mediated by structural reorganization of the nuclear pore basket.
AB  - Messenger RNA leaves the cell nucleus as ribonucleoprotein (RNP) particles. The
      nucleocytoplasmic translocation of the particles takes place through the nuclear
      pore complex (NPC) and includes two steps: binding to the NPC and transit through
      its central channel. The NPC basket is a fishtrap-like component of NPC facing
      the nucleoplasm. Its position in the NPC strongly suggests that it has an
      important role in the initial steps of macromolecular export from the nucleus.
      Here we report a cyclic rearrangement of the basket structure in relation to the
      translocation of a specific messenger RNP (mRNP) of exceptional size, the
      Balbiani ring RNP particles in the salivary gland cells in Chironomus. We used
      field emission in-lens scanning electron microscopy (FEISEM), transmission
      electron microscopy (TEM), and immunocytochemistry to analyse the structural
      organization of the basket during the mRNP export. Our observations reveal five
      configurations of the basket which are presented in a model of basket
      reorganization related to the state of mRNP penetration into the NPC. We suggest
      that the functional role of the basket is to anchor the mRNP particle to the NPC
      and position it in correct orientation at the entrance to the central channel of
      the NPC.

PMID- 8757795
TI  - Reversible pH-dependent conformational change of reconstituted influenza
      hemagglutinin.
AB  - Fusion between influenza virus and cell membranes is mediated by a major acid
      induced conformational change of the spike glycoprotein of the viral envelope,
      hemagglutinin (HA). The conformational change of HA is commonly believed to be a
      kinetically controlled irreversible process, although the experimental evidence
      for this is controversial. Here we show by polarized infrared spectroscopy that
      the previously described acid-induced inclination of HA reconstituted in
      supported phospholipid bilayers is reversible in the absence, but irreversible in
      the presence, of bound target membranes. We also demonstrate reversible pH
      dependent changes in the capability of reconstituted HA to bind target membranes.
      These results support a thermodynamically controlled mechanism of the
      conformational change of HA and provide new insight into the understanding of the
      energetics of influenza-mediated membrane fusion.

PMID- 8757796
TI  - Repressor forms of the enhancer-binding protein NrtC: some fail in coupling ATP
      hydrolysis to open complex formation by sigma 54-holoenzyme.
AB  - NtrC (nitrogen regulatory protein C) is a bacterial enhancer-binding protein that
      activates transcription by catalyzing isomerization of closed complexes between
      sigma54-holoenzyme and a promoter to open complexes. To catalyze this reaction,
      NtrC must be phosphorylated and form an appropriate oligomer so that it can
      hydrolyze ATP. NtrC can also repress transcription by sigma70-holoenzyme. In this
      paper we characterize "repressor" mutant forms of NtrC from Salmonella
      typhimurium, forms that have lost the ability to activate transcription by
      sigma54-holoenzyme (in vitro activity at least 1000-fold lower than wild-type)
      but retain the ability to repress transcription by sigma70-holoenzyme. The amino
      acid substitutions in NtrCrepressor proteins that were obtained by classical
      genetic techniques alter residues in the central domain of the protein, the
      domain directly responsible for transcriptional activation. Commensurate with
      this, phosphorylation and the autophosphatase activities of NtrCrepressor
      proteins, which are functions of the amino-terminal regulatory domain of NtrC,
      are normal. In addition, these proteins have essentially normal DNA-binding,
      which is a function of the C-terminal region of NtrC and bind cooperatively to
      enhancers. (The NtrC(G219K) protein has "improved" DNA-binding, which is
      discussed.) We previously presented evidence that several NtrCrepressor proteins
      have impaired ATPase activity. We now show that two other repressor proteins,
      NtrC(A216V) and NtrC(A220T), have as much ATPase activity as wild-type NtrC when
      they are phosphorylated and bound to an enhancer and that they have considerably
      more activity than an unphosphorylated NtrC(constitutive) protein, which is
      capable of activating transcription. These results demonstrate that NtrC(A216V)
      and NtrC(A220T) fail in a function of the central domain other than ATPase
      activity. Although they may fail in contact with sigma54-holoenzyme per se, the
      fact that alanine is the amino acid normally found at these positions leads us to
      speculate that these proteins fail in coupling energy to a change in conformation
      of the polymerase.

PMID- 8757797
TI  - In vitro characterization of transcription termination factor Rho from
      Escherichia coli rho(nusD) mutants.
AB  - Escherichia coli nusD strains are bacteria that carry mutations in rho, the gene
      for transcription termination factor Rho, that block the growth of phages T4 and
      lambdar32. We have identified the rho mutation in six independent nusD strains,
      and although five of the strains have different mutations, with one exception the
      mutations are in the proposed RNA-binding domain of Rho. We overexpressed,
      purified, and characterized the five different mutant Rho proteins. All show
      substantial RNA-dependent ATPase activity with several homoribopolymers or the
      lambda cro message as cofactor. At the lambda tR1 Rho-dependent terminator in
      vitro, all mutant Rho proteins show decreased termination compared with wild
      type, and all also terminate within cro at a new terminator, tRE, with endpoints
      5' to tR1 at 170, 200, 245 and 260 nucleotides 3' from the transcription start.
      The mutant Rho proteins are proposed to interfere with bacteriophage T4 growth
      through indirect effects on host gene expression.

PMID- 8757798
TI  - The mechanism of early transcription termination by Rho026.
AB  - We previously found that nusD-type mutations in Escherichia coli transcription
      termination factor Rho enhance in vitro transcription termination at four points
      within the lambdacro gene. Here we show that the early termination points are
      part of one Rho-dependent termination site, tRE, with properties like those of
      previously characterized Rho-dependent sites lamda tR1 and trpt'. The early
      termination points are all RNA polymerase pause sites, and by deletion analysis
      and oligonucleotide blocking experiments, a common 5' Rho entry site for the
      early termination points (rutE) is identified. We show that both Rho026 and Rho+
      can use rutE as an entry point for termination, but that Rho026 is more efficient
      in releasing the nascent RNA at tRE. The RNA-dependent ATPase activities of wild
      type and mutant Rhos are similar, as are their abilities to bind free RNA and to
      use (rC)10 oligomers for ATPase activation. We therefore suggest that Rho-RNA
      polymerase interactions that define the site of RNA 3' end formation are altered
      in NusD Rho mutants. NusD Rho mutants are less dependent on, but still responsive
      to, the transcription termination factor NusG. However, addition of NusG to in
      vitro termination assays allows Rho+ to terminate more efficiently at tRE. These
      results suggest that NusG aids in the 3' end formation process. The decreased
      dependence on NusG for termination by the mutant Rhos in vitro provides an
      explanation for poorer lambda growth in rho(nusD) cells by interference with
      lamdaN-mediated antitermination at Rho-dependent sites.

PMID- 8757799
TI  - Mimicking somatic hypermutation: affinity maturation of antibodies displayed on
      bacteriophage using a bacterial mutator strain.
AB  - Human antibodies can now be isolated from antibody repertoires displayed on the
      surface of filamentous bacteriophage in a process that mimics the primary immune
      response. Here we have attempted to mimic the secondary response, the natural
      process of affinity maturation of antibodies occurring in germinal centres, by
      multiple cycles of random mutation and selection. Phage displaying a human
      antibody fragment recognising the hapten 2-phenyl-5-oxazolone were grown in a
      mutator strain of bacteria (Escherichia coli: mutD5) to generate a large
      repertoire of antibodies that should include the majority of possible single
      nucleotide point mutations. The repertoire of phage antibody mutants was then
      selected by binding to hapten. By multiple rounds of growth in the mutator
      strain, and increasingly stringent selection, we succeeded in isolating mutants
      with improved binding affinities; furthermore, the distribution of mutations and
      nucleotide substitution preferences strongly resembled those of somatic
      hypermutation. We then constructed a genealogical tree from the sequences of
      mutants taken at different rounds, and identified four sequentially acquired
      mutations that together improve the binding affinity of the antibody by a factor
      of 100-fold (from Kd 320 nM to 3.2 nM).

PMID- 8757800
TI  - In vitro protein-primed initiation of pneumococcal phage Cp-1 DNA replication
      occurs at the third 3' nucleotide of the linear template: a stepwise sliding-back
      mechanism.
AB  - Phage Cp-1 from Streptoccocus pneumoniae makes use of a protein-priming mechanism
      to start replication of its linear DNA: the first reaction consists of the
      addition of 5' dAMP to a molecule of the primer protein, an initiation event
      occurring at both DNA ends. After elongation of the initiation complex, the
      primer protein remains linked to the 5' end of the nascent DNA chain, and is
      subsequently referred to as terminal protein (TP). In this paper, using DNA-free
      extracts from Cp-1-infected S. pneumoniae, we provide evidence that the formation
      of the covalent complex TP-dAMP is a template-instructed reaction and that ssDNA
      molecules can serve as templates for TP-primed replication. A mutational analysis
      of the 3' terminal nucleotides of Cp-1 DNA reveals that a precise DNA sequence is
      required for efficient template recognition, and that in vitro initiation of Cp-1
      DNA replication is directed by the third nucleotide of the template. However, the
      two terminal nucleotides are recovered during the first steps of elongation. A
      new variant of the sliding-back mechanism for protein-primed initiation, firstly
      described for Bacillus subtilis phage phi29, is proposed to account for the
      maintenance of Cp-1 DNA ends. The results presented here reinforce the hypothesis
      that sliding-back must be a common feature in all genomes that use protein
      priming to initiate replication.

PMID- 8757801
TI  - Determination of the number and location of the manganese binding sites of DNA
      quadruplexes in solution by EPR and NMR in the presence and absence of thrombin.
AB  - The interaction of a DNA quadruplex with thrombin has been studied by first
      determining the sites of manganese binding to the quadruplex in the absence of
      thrombin. This has been followed by determining if the interactions with thrombin
      displace the bound manganese. A different DNA quadruplex has also been studied as
      a control. The refined solution structures of two DNA quadruplexes have been used
      to predict the electrostatic potentials of these DNAs. The calculated
      electrostatic potentials have been used to predict the locations of the binding
      sites of the paramagnetic ion manganese to these DNAs. The enhanced relaxation of
      DNA protons due to the binding of the paramagnetic metal ion Mn2+ has been used
      to experimentally determine the locations of the binding sites. The NMR results
      and the predictions based on the electrostatic potentials both place the binding
      sites of the manganese in the narrow grooves of these quadruplex DNAs. The
      predicted locations are spatially close to those experimentally observed, and the
      predicted and experimental locations also have similar electrostatic potential
      energy. These results have allowed a validation of the predictions of
      electrostatic potentials from structure. The 15mer quadruplex has two strong Mn2+
      binding sites with one in each narrow groove. Both Mn2+ are released when the
      15mer is complexed with thrombin, indicating that both narrow grooves are
      involved in the 15mer-thrombin interactions. The dimer quadruplex has a different
      structural motif than the 15mer and the presence of thrombin does not appreciably
      affect its interactions with Mn2+.

PMID- 8757802
TI  - Structure of the CAP-DNA complex at 2.5 angstroms resolution: a complete picture
      of the protein-DNA interface.
AB  - The crystallographic structure of the CAP-DNA complex at 3.0 A resolution has
      been reported previously. For technical reasons, the reported structure had been
      determined using a gapped DNA molecule lacking two phosphates important for CAP
      DNA interaction. In this work, we report the crystallographic structure of the
      CAP-DNA complex at 2.5 A resolution using a DNA molecule having all phosphates
      important for CAP-DNA interaction. The present resolution permits unambiguous
      identification of amino acid-base and amino acid-phosphate hydrogen bonded
      contacts in the CAP-DNA complex. In addition, the present resolution permits
      accurate definition of the kinked DNA conformation in the CAP-DNA complex.

PMID- 8757803
TI  - Carbohydrate and protein-based inhibitors of porcine pancreatic alpha-amylase:
      structure analysis and comparison of their binding characteristics.
AB  - The crystal structures of porcine pancreatic alpha-amylase isozyme II (PPA II) in
      its free form and complexed with the trestatin A derived pseudo-octasaccharide V
      1532 have been determined using Patterson search techniques at resolutions of 2.3
      and 2.2 angstroms, respectively. Seven rings of the competitive inhibitor V-1532
      could be detected in the active site region as well as two maltose units in
      secondary binding sites on the surface. V-1532 occupies the five central sugar
      binding subsites similar to the PPA/acarbose structure. A sixth ring exists at
      the reducing end, connecting two symmetry related PPA molecules. The seventh
      moiety, a 6-hydroxymethylconduritol ring, is located at the non-reducing end. The
      electron density for this ring is relatively weak, indicating considerable
      disorder. This study shows that PPA is able to accommodate more than five rings
      in the active site region, but that additional rings would increase the binding
      affinity only slightly, which is in accordance with kinetic experiments. A
      comparison of the structures of free PPA, PPA/V-1532 and PPA/Tendamistat shows
      the characteristic conformational changes that accompany inhibitor binding and
      distinguish pseudo-oligosaccharide inhibitors from proteinaceous inhibitors.
      Although both classes of inhibitors block the sugar binding subsites in the
      active site region, the extreme specificity and binding affinity of the
      proteinaceous inhibitors is probably due to an intricate interaction pattern
      involving areas further away from the catalytic center.

PMID- 8757804
TI  - The 1.6 angstroms resolution crystal structure of nuclear transport factor 2
      (NTF2).
AB  - Nuclear transport factor 2 (NTF2) facilitates protein transport into the nucleus
      and interacts with both the small Ras-like GTPase Ran and nucleoporin p62. We
      have determined the structure of bacterially expressed rat NTF2 at 1.6 angstroms
      resolution using X-ray crystallography. The NTF2 polypeptide chain forms an alpha
      + beta barrel that opens at one end to form a distinctive hydrophobic cavity and
      its fold is homologous to that of scytalone dehydratase. The NTF2 hydrophobic
      cavity is a candidate for a potential binding site for other proteins involved in
      nuclear import such as Ran and nucleoporin p62. In addition, the hydrophobic
      cavity contains a putative catalytic Asp-His pair, which raises the possibility
      of an unanticipated enzymatic activity of the molecule that may have implications
      for the molecular mechanism of nuclear protein import.

PMID- 8757805
TI  - Native-like beta-structure in a trifluoroethanol-induced partially folded state
      of the all-beta-sheet protein tendamistat.
AB  - The effect of trifluoroethanol (TFE) on the structure of the all-beta-sheet
      protein tendamistat was investigated. At low concentrations TFE induces
      cooperative loss of the native tertiary structure leading to a partially folded
      state. The loss of specific side-chain interactions in the transition from the
      native state of the TFE-induced state is demonstrated by the disappearance of the
      CD bands in the aromatic region, a reduced chemical shift dispersion of the one
      dimensional 1H NMR spectrum and a broad, uncooperative thermal unfolding
      transition of the partially folded state. An increased line-width of the NMR
      bands in the TFE state compared with the unfolded state suggests the presence of
      multiple, rapidly interconverting conformations. Hydrogen-exchange studies of
      amide proteins in the TFE state reveal the existence of defined hydrogen bonds at
      the same locations as in the native state, but with largely reduced stability.
      This suggests the presence of most of the native beta-sheet structure. These
      results are supported by Fourier transformed IR measurements, which show nearly
      the same amount of beta-structure in the TFE state and in the native state. Far
      UV CD spectroscopy suggests the induction of some alpha-helical structure upon
      addition of TFE, which appears to be located mainly in regions corresponding to
      loops or random structure in the native state and which seems to represent
      fluctuating conformations with preferred backbone angles rather than stable,
      hydrogen-bonded alpha-helices. These results show that stable non-local
      interactions, as they occur in beta-sheets, can form in the absence of specific
      side-chain interactions. The presence of a subset of the native long-range
      interactions and the absence of stable non-native interactions suggests that the
      observed partially folded state might represent an early intermediate on a
      hierarchical folding pathway of tendamistat.

PMID- 8757806
TI  - A concerted tryptophanyl-adenylate-dependent conformational change in Bacillus
      subtilis tryptophanyl-tRNA synthetase revealed by the fluorescence of Trp92.
AB  - A semi-conserved tryptophan residue of Bacillus subtilis tryptophanyl-tRNA
      synthetase (TrpRS) was previously asserted to be an essential residue and
      directly involved in tRNATrp binding and recognition. The crystal structure of
      the Bacillus stearothermophilus TrpRS tryptophanyl-5'-adenylate complex (Trp-AMP)
      shows that the corresponding Trp91 is buried and in the dimer interface, contrary
      to the expectations of the earlier assertation. Here we examine the role of this
      semi-conserved tryptophan residue using fluorescence spectroscopy. B. subtilis
      TrpRS has a single tryptophan residue, Trp92. 4-Fluorotryptophan (4FW) is used as
      a non-fluorescent substrate analog, allowing characterization of Trp92
      fluorescence in the 4-fluorotryptophanyl-5'-adenylate (4FW-AMP) TrpRS complex.
      Complexation causes the Trp92 fluorescence to become quenched by 70%. Titrations,
      forming this complex under irreversible conditions, show that this quenching is
      essentially complete after half of the sites are filled. This indicates that a
      substrate-dependent mechanism exists for the inter-subunit communication of
      conformational changes. Trp92 fluorescence is not efficiently quenched by small
      solutes in either the apo- or complexed form. From this we conclude that this
      tryptophan residue is not solvent exposed and that binding of the Trp92 to
      tRNATrp is unlikely. Time-resolved fluorescence indicates conformational
      heterogeneity of B. subtilis Trp92 with the fluorescence decay being best
      described by three discrete exponential decay times. The decay-associated spectra
      (DAS) of the apo- and complexed-TrpRS show large variations of the concentration
      of individual fluorescence decay components. Based on recent correlations of
      these data with changes in the local secondary structure of the backbone
      containing the fluorescent tryptophan residue, we conclude that changes observed
      in Trp92 time-resolved fluorescence originate primarily from large perturbations
      of its local secondary structure. The quenching of Trp92 in the 4FW-AMP complex
      is best explained by the crystal structure conformation, in which the tryptophan
      residue is found in an alpha-helix. The amino acid residue cysteine is observed
      clearly within the quenching radius (3.6 angstroms) of the conserved tryptophan
      residue. These tryptophan and cysteine residues are neighbors, one helical turn
      apart. If this local alpha-helix was disrupted in the apo-TrpRS, this disruption
      would concomitantly relieve the putative cysteine quenching by separating the two
      residues. Hence we propose a substrate-dependent local helix-coil transition to
      explain both the observed time-resolved and steady-state fluorescence of Trp92. A
      mechanism can be further inferred for the inter-subunit communication involving
      the substrate ligand Asp132 and a small alpha-helix bridging the substrate
      tryptophan residue and the conserved tryptophan residue of the opposite subunit.
      This putative mechanism is also consistent with the observed pH dependence of
      TrpRS crystal growth and substrate binding. We observe that the mechanism of
      TrpRS has a dynamic component, and contend that conformational dynamics of
      aminoacyl-tRNA synthetases must be considered as part of the molecular basis for
      the recognition of cognate tRNA.

PMID- 8757807
TI  - Easily searched protein folding potentials.
AB  - In order to calculate the tertiary structure of a protein from its amino acid
      sequence, the thermodynamic approach requires a potential function of sequence
      and conformation that has its global minimum at the native conformation for many
      different proteins. Here we study the behavior of such functions for the simplest
      model system that still has the essential features of the protein folding
      problem, namely two-dimensional square lattice chain configurations involving two
      residue types. First we demonstrate a method for accurately recovering the given
      contact potential from only a knowledge of which sequences fold to which
      structures and what the non-native structures are. Second, we show how to derive
      from the same information more general potential functions having much better
      positive correlations between potential function value and conformational
      deviation from the native. These functions consequently permit faster and more
      reliable searches for the native conformation, given the native sequence.
      Furthermore, the method for finding such potentials is easily applied to more
      realistic protein models.

PMID- 8757808
TI  - Transient and persistent experimental infection of nonhuman primates with
      Helicobacter pylori: implications for human disease.
AB  - Helicobacter pylori can establish chronic infection in the human gastric mucosa,
      and it is a major cause of peptic ulcer disease and a principal risk factor for
      gastric cancer. This creates a need for H. pylori infection models that mimic the
      human condition. To test the suitability of rhesus monkeys as infection models,
      H. pylori-free animals were inoculated intragastrically with mixtures of H.
      pylori strains, bacteria recovered from colonized animals were typed by
      arbitrarily primed PCR, and host inflammatory and immunologic responses were
      monitored. Among five H. pylori-free animals inoculated with a mixture of two
      human strains plus one monkey strain, one became persistently infected and one
      became only transiently infected. The recovered bacteria matched the monkey input
      strain in DNA fingerprint. A subsequent trial using two new human isolates and
      three animals that had resisted colonization by the monkey strain resulted in
      persistent infection in one animal and transient infection in two others. Antral
      gastritis, anti-H. pylori serum immunoglobulin G, and atrophy all increased, but
      with patterns that differed among animals. We conclude that (i) rhesus monkeys
      can be infected experimentally with H. pylori, (ii) individuals differ in
      susceptibility to particular bacterial strains, (iii) infections may be
      transient, and (iv) the fitness of a particular strain for a given host helps
      determine the consequences of exposure to that strain.

PMID- 8757809
TI  - Plasmodium falciparum stimuli for human gammadelta T cells are related to
      phosphorylated antigens of mycobacteria.
AB  - The presence in Plasmodium falciparum of a mitogenic factor for the major human
      blood gammadelta T-cell subset has been known for years. These gammadelta T cells
      bearing T-cell receptor Vgamma9 and Vdelta2 variable regions also respond to
      Mycobacterium tuberculosis, through recognition of several phosphorylated
      nonpeptidic antigens. In this study, we undertook a better characterization of
      the malarial stimulus and show that the polygonal activation of Vgamma9/Vdelta2
      gammadelta T cells by P. falciparum schizonts is also and exclusively
      attributable to two phosphorylated malarial compounds. The finding of such
      stimuli in eukaryotic cells evidence an antigenic link between intracellular
      parasites as different as Plasmodium and Mycobacterium species. Hence,
      phosphorylated antigens could be involved in a common pattern of transdisease T
      cell responses against various human pathogens.

PMID- 8757810
TI  - Capsular polysaccharide of Cryptococcus neoformans induces proinflammatory
      cytokine release by human neutrophils.
AB  - Human polymorphonuclear leukocytes from normal subjects produced proinflammatory
      cytokines in response to stimulation with Cryptococcus neoformans yeast cells.
      The cytokines released after stimulation of neutrophils included interleukin
      1beta (IL-1beta), IL-6, IL-8 and tumor necrosis factor alpha. The magnitude of
      the cytokine response was related to the yeast capsule size. Cells of a large
      capsule isolate stimulated release of greater amounts of cytokine than did a
      thinly encapsulated isolate, which, in turn, stimulated release of greater
      amounts of cytokine than an acapsular isolate. Cytokine release was also
      stimulated by supernatant fluids from cryptococcal cells that were preincubated
      with 10% human serum, suggesting the generation of a soluble mediator. The major
      capsular polysaccharide, glucuronoxylomannan, stimulated release of tumor
      necrosis factor alpha, IL-1beta, and IL-8 in a dose-dependent fashion. These
      results differ from previous studies of cytokine secretion by human monocytes in
      several important respects, including the importance of encapsulation in
      stimulation of cytokine secretion and the ability of purified glucuronoxylomannan
      to induce cytokine secretion.

PMID- 8757811
TI  - The major surface protein complex of Treponema denticola depolarizes and induces
      ion channels in HeLa cell membranes.
AB  - The oral spirochete Treponema denticola is closely associated with periodontal
      diseases in humans. The 53-kDa major surface protein (Msp) located in the outer
      membrane of T. denticola serovar a (ATCC 35405) has both pore-forming activity
      and adhesin activity. We have used standard patch clamp recording methods to
      study the effects of a partially purified outer membrane complex containing Msp
      on HeLa cells. The Msp complex was free of the chymotrypsin-like proteinase also
      found in the outer membrane of T. denticola. Msp bound to several HeLa cell
      proteins, including a 65-kDa surface protein and a 96-kDa cytoplasmic protein.
      The Msp complex depolarized and increased the conductance of the HeLa cell
      membrane in a manner which was not strongly selective for Na+, K+, Ca2+, and Cl-
      ions. Cell-attached patches of HeLa cell membrane exposed to Msp complex
      exhibited short-lived channels with a slope conductance of 0.4 nS in
      physiologically normal saline. These studies show that Msp binds both a putative
      epithelial cell surface receptor and cytoplasmic proteins and that the Msp
      complex can form large conductance ion channels in the cytoplasmic membrane of
      epithelial cells. These properties may contribute to the cytopathic effects of T.
      denticola on host epithelial cells.

PMID- 8757812
TI  - Identification of a transferrin-binding protein from Borrelia burgdorferi.
AB  - Bacterial pathogens have evolved various strategies to acquire iron from the iron
      restricted environment found in mammalian hosts. Borrelia burgdorferi should be
      no different with regard to its requirement for ferric iron, and previous studies
      have suggested that transferrin (Tf) may be a source of iron in vivo. By probing
      blots with Tf conjugated to horseradish peroxidase, we have identified an outer
      membrane protein (28 kDa) from B. burgdorferi B31 that bound holo-Tf but not apo
      Tf. The 28-kDa protein bound human, rat, or mouse Tf and was produced only by low
      passage (less than passage 5), virulent isolates of strain B31. In addition, the
      Tf-binding protein (Tbp) from strain B31 retained the ability to bind Tf after
      treatment with 2% sodium dodecyl sulfate-1% beta-mercaptoethanol and heating to
      100 degrees C for 5 min. These properties are remarkably similar to those of the
      Tbp of Staphylococcus aureus and Tbp2 from Neisseria meningitidis. B. burgdorferi
      Sh-2-82 produced an outer membrane protein different in size, i.e., 26 kDa, but
      with properties similar to those of to the protein from strain B31, suggesting
      variation in B. burgdorferi Tbps. The exact role of the 28-kDa protein in iron
      acquisition by B. burgdorferi remains to be determined.

PMID- 8757813
TI  - Epidermal growth factor-binding protein in Mycobacterium avium and Mycobacterium
      tuberculosis: a possible role in the mechanism of infection.
AB  - Epidermal growth factor (EGF) is a potent mitogen for a variety of eukaryotic
      cells. EGF is found in a number of tissues and is prevalent in necrotic tissues
      and granulomata. The biological effect of EGF on mammalian cells is initiated by
      the binding to a specific receptor. Both Mycobacterium avium and Mycobacterium
      tuberculosis cause lung infections and localized or disseminated disease in both
      patients without AIDS and those with AIDS. Histopathologic studies show necrosis
      in the lung, liver, and splenic tissues of patients with disseminated
      mycobacterial infection. In the course of experiments to examine the effect of
      growth factors on macrophages, it was observed that M. avium and M. tuberculosis
      but not Mycobacterium smegmatis cultured in the presence of 5, 50, or 500 ng of
      EGF per ml grew significantly faster than mycobacteria cultured in the absence of
      EGF. 125I-EGF was found to bind to M. avium and M. tuberculosis, and the binding
      was competitively inhibited by unlabeled EGF. A receptor for EGF was identified
      on mycobacteria. Incubation of mycobacteria with EGF prior to infection of
      macrophage monolayers resulted in faster bacterial growth within macrophages
      compared with that of mycobacteria not incubated with EGF. EGF-binding protein
      was cloned and expressed in Escherichia coli, and subsequently the protein was
      purified and the N-terminal amino acids were sequenced. These results suggest
      that EGF is a growth factor for pathogenic mycobacteria in granulomatous tissues
      and within macrophages and might enhance growth rates of both intracellular and
      extracellular mycobacteria in the site of infection.

PMID- 8757814
TI  - The Bcg/Ity/Lsh locus: genetic transfer of resistance to infections in C57BL/6J
      mice transgenic for the Nramp1 Gly169 allele.
AB  - The murine Bcg/Ity/Lsh locus determines the susceptibilities of inbred strains to
      infection with unrelated intracellular parasites, such as Mycobacterium bovis,
      Salmonella typhimurium, and Leishmania donovani. A candidate for Bcg/Ity/Lsh,
      designated Nramp1, has been recently identified and shown to encode a novel
      integral membrane protein that is expressed exclusively in professional
      phagocytes but whose function remains unknown. In inbred strains, the
      susceptibility to infection is associated with a single glycine-to-aspartic acid
      substitution at position 169 (G169D) in the predicted TM4 of the protein. To
      confirm the candidacy of Nramp1 as Bcg/Ity/Lsh and to determine the importance of
      the G169D mutation on Nramp1 function, we constructed transgenic mice in which
      the G169 allele of Nramp1 was transferred onto the background of a homozygous
      D169 allele. These transgenic mice were analyzed for their sensitivity to
      infections under the control of Bcg/Ity/Lsh. The transgene constructed for these
      studies contained the entire Nramp1G169 gene together with approximately 5 kb of
      sequences upstream of the transcription initiation site of this gene. We observed
      that these sequences were sufficient to direct Nramp1G169 expression in
      transgenic macrophages, resulting in the appearance of a mature protein of 90 to
      100 kDa over a background of Nramp1G169 characterized by the complete absence of
      the mature Nramp1 polypeptide. The appearance of the Nramp1G169-encoded protein
      in transgenic macrophages was concomitant with the emergence of resistance to
      infection by M. bovis BCG, as measured by the extent of bacteria] replication in
      the spleen, and by S. typhimurium, as measured by survival after an intravenous
      challenge. The gain of function detected in transgenic Nramp1G169 animals
      establishes unambiguously that Nramp1 and Bcg/Ity/Lsh are allelic.

PMID- 8757815
TI  - Specific induction of fibronectin binding activity by hemoglobin in Candida
      albicans grown in defined media.
AB  - Fibronectin (FN) is a major component of host extracellular matrix that may play
      an important role in the initiation and dissemination of Candida albicans
      infections. Expression of FN binding requires growth of C albicans blastoconidia
      in complex medium, and the regulation of FN receptor expression is poorly
      understood. We now demonstrate that hemoglobin is a potent and specific inducer
      of FN receptor expression and describe a defined medium supplemented with
      hemoglobin that greatly and stably enhances the binding activity of C. albicans
      for soluble FN. Enhancement of FN binding by hemoglobin in strain 44807 was
      concentration dependent and was maximal at 0.1% hemoglobin with 20- to 80-fold
      enhancement. The hemoglobin-induced FN binding to C. albicans was saturable, with
      a Kd of 2.7 X 10(-8) M. Enhancement required growth of C. albicans in hemoglobin
      containing medium, since simply exposing blastoconidia to hemoglobin in a
      nongrowing status did not enhance binding. Induction was reversible following
      removal of hemoglobin from the growth medium and not associated with germination.
      Inorganic or protein-bound iron was not sufficient for the induction, since other
      iron-containing proteins or inorganic iron salts were inactive. Growth in the
      simple medium yeast nitrogen base supplemented with hemoglobin increased cell
      adhesion to immobilized FN and to cultured monolayers of bovine corneal
      endothelial cells. These data suggest that hemoglobin may be an important
      regulator of FN binding activity in C. albicans and thus may play a role in its
      pathogenesis.

PMID- 8757816
TI  - Induction of an extracellular esterase from Candida albicans and some of its
      properties.
AB  - An extracellular esterase from Candida albicans A-714 was found to be induced in
      a medium containing 0.7% yeast nitrogen base and 2.5% Tween 80
      (polyoxyethylenesorbitan compounds). Enzyme activity, which exists predominantly
      in the extracellular space, was measured by a colorimetric method using alpha
      naphthyl palmitate as a substrate. The induction level of the esterase activity
      was found to be well correlated with fungal growth and was dependent on the Tween
      80 concentration. Such esterase activity was observed only in medium containing
      Tween 80 or other Tweens as the sole carbon source and therefore was not observed
      in either peptone-glucose medium or peptone-glucose medium supplemented with
      Tween 80. The induced esterase was heat labile and had maximum activity at pH
      5.5. Enzyme activity was stimulated by the addition of sodium taurocholate, an
      activator of lipase. Thin-layer chromatography revealed that this enzyme does not
      hydrolyze triolein and L-alpha-lecithin, suggesting that it is a monoester
      hydrolase (not a lipase in the strict sense of the word). Esterase activity was
      examined in 85 clinical isolates of Candida species; C. albicans, C. tropicalis,
      and C. parapsilosis tended to have higher enzyme activities than C. kefyr, C.
      krusei, C. glabrata, and C. guilliermondii. Although the physiological properties
      of this esterase are not clear at present, it was found to be crucial for fungal
      growth under specific conditions.

PMID- 8757817
TI  - Role of gamma interferon in a neonatal mouse model of group B streptococcal
      disease.
AB  - The aim of this study was to assess the role of gamma interferon (IFN-gamma) in a
      neonatal mouse model of group B streptococcal (GBS) sepsis. IFN-gamma was
      produced by spleen cells at 24, 48, and 72 h after GBS challenge. Treatment with
      anti-IFN-gamma at 6 h before challenge totally abrogated the IFN-gamma response
      but did not affect survival. Subcutaneous administration of recombinant IFN-gamma
      (2,500 IU per pup) at 18 h after challenge resulted in increased survival time
      and reduced blood colony counts at 48 and 72 h. In vitro preincubation of
      neonatal whole blood with IFN-gamma before the addition of GBS resulted in
      significant restriction of bacterial growth. These data indicate that
      administration of recombinant IFN-gamma can partially restore impaired host
      defenses against GBS in neonatal mice. This cytokine may be useful for the
      treatment of neonatal infections.

PMID- 8757818
TI  - Miller-Fisher syndrome associated with Campylobacter jejuni bearing
      lipopolysaccharide molecules that mimic human ganglioside GD3.
AB  - A Campylobacter jejuni strain of serotype O:10 was isolated from a patient who
      had Miller-Fisher syndrome. In its biochemical reactions and cellular morphology,
      the isolate was characteristic of typical C. jejuni. Antibodies against extracted
      lipopolysaccharide (LPS) were detected by passive hemagglutination in the acute-
      and convalescent-phase patient sera. By sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and immunoblotting with the O:10 antiserum, it was demonstrated
      that the strain possessed both low- and high-molecular-weight molecules. Chemical
      analysis of the LPS revealed that the core oligosaccharide has a terminal
      trisaccharide epitope consisting of two molecules of sialic acid linked to
      galactose, a structure reflecting the terminal region of human ganglioside GD3.
      As this trisaccharide is also present in LPS cores of serotype O:19 strains from
      patients with Guillain-Barre syndrome but not in cores of nonneuropathic C.
      jejuni, a possible role for the trisaccharide in the etiology of neuropathies is
      indicated, and a difference for distinguishing neuropathic strains from
      nonneuropathic strains may be the presence of a sialyltransferase required for
      the synthesis of this trisaccharide.

PMID- 8757819
TI  - Antibody-independent effector mechanisms in resistance to the intestinal nematode
      parasite Trichuris muris.
AB  - The development of a strong Th2-type immune response is essential in resistance
      to the intestinal nematode parasite Trichuris muris. Although the underlying cell
      regulatory mechanisms important in protective immunity are well defined, the
      actual Th2-controlled effector mechanisms culminating in worm expulsion are
      uncharacterized. Using methodology involving the selective reconstitution of
      severe combined immunodeficiency mice with highly pure populations of CD4+ T
      cells from immune BALB/c donors, we show here that antibody is not an essential
      component in resistance to T. muris. Thus, CD4+ T cells purified from BALB/c
      donor mice at a time point when Th2 cells are in dominance (days 19 to 21
      postinfection) confer resistance to infection on recipient severe combined
      immunodeficiency mice in the complete absence of an antibody response.

PMID- 8757820
TI  - Immunity against Yersinia enterocolitica by vaccination with Yersinia HSP60
      immunostimulating complexes or Yersinia HSP60 plus interleukin-12.
AB  - Microbial heat shock proteins (HSP) are dominant antigens for the host immune
      response. Because of the high sequence homology between mammalian and microbial
      HSP, their value as component of a subunit vaccine has been the subject of
      controversy. Previous work from this laboratory, however, demonstrated for the
      first time that the adoptive transfer of HSP60-reactive CD4+ alphabeta T-cell
      clones confers protection against bacterial infection in mice but does not induce
      autoimmunity. In the present study, we have therefore evaluated the potential
      role of Yersinia HSP60 (Y-HSP60) as a vaccine in the Yersinia enterocolitica
      mouse infection model. For this purpose, immunostimulating complexes (ISCOM)
      which included Y-HSP60 were constructed. Parenteral administration of this
      vaccine induced high Y-HSP60-specific serum antibody responses as well as T-cell
      responses. This reaction was parallelled by immunity against a lethal challenge
      with Y. enterocolitica. In contrast, mucosal application of Y-HSP60-ISCOM failed
      to induce systemic Y-HSP60-specific T-cell responses and thus failed to induce
      immunity against yersiniae. Likewise, vaccination with purified recombinant Y
      HSP60 induced antibody responses but only weak T-cell responses. Therefore, this
      vaccination protocol was not protective. However, when interleukin-12 was used as
      an adjuvant, purified Y-HSP60 induced significant Y-HSP60-specific T-cell
      responses and thus induced protection against subsequent challenge with
      yersiniae. These studies suggest that (i) microbial HSP might be promising
      candidates for the design of subunit vaccines and (ii) interleukin-12 is an
      efficient alternative adjuvant to ISCOM particles for induction of protective CD4
      Th1-cell-dependent immune responses against bacterial pathogens.

PMID- 8757821
TI  - Th1-like antifilarial immune responses predominate in antigen-negative persons.
AB  - To characterize immune responses associated with the putatively immune state in
      bancroftian filariasis (that is, both microfilaria and antigen free), humoral and
      cellular responses were compared among antigen- and microfilaria-negative,
      antigen-positive and microfilaria-negative, and microfilaria-positive
      individuals. Antifilarial isotype levels were measured by enzyme-linked
      immunosorbent assay. Peripheral blood mononuclear cell responses were measured by
      proliferation, by bioassay for interleukin-2 (IL-2) and IL-10, and by reverse
      transcription-PCR for IL-4, IL-5, and gamma interferon. The absence of
      circulating filarial antigen was associated with Th1-like responses, including
      significantly higher proliferative (P < 0.001) and IL-2 (P = 0.008) responses and
      a higher prevalence of gamma interferon (0.02 < P < 0.1) responses. Significantly
      elevated antifilarial immunoglobulin G4 (IgG4) levels (P = 0.0035) were
      associated with antigenemia, whereas microfilaremia was associated with
      significantly decreased antifilarial IgG2 levels (P = 0.0014). IL-4 mRNA levels
      were not significantly different among the three groups; however, there was a
      subpopulation of microfilaremic individuals who did not make detectable levels of
      IL-4 mRNA and who produced low antifilarial IgG4 levels compared with those of
      individuals who had detectable levels of IL-4 mRNA. IL-5 mRNA levels also were
      not significantly different among groups; however, more microfilaremic
      individuals produced IL-5 mRNA in response to adult filarial antigens, and total
      parasite-specific IL-4 and IL-5 mRNA levels were significantly correlated (P =
      0.05). Although longitudinal data are not currently available, the elevated Th1
      like responses in antigen- and microfilaria-negative individuals are consistent
      with the hypothesis that these responses contribute to protection in putatively
      immune individuals.

PMID- 8757822
TI  - Mechanism of membrane damage by El Tor hemolysin of Vibrio cholerae O1.
AB  - El Tor hemolysin (ETH; molecular mass, 65 kDa) derived from Vibrio cholerae O1
      spontaneously assembled oligomeric aggregates on the membranes of rabbit
      erythrocyte ghosts and liposomes. Membrane-associated oligomers were resolved by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting into
      two to nine bands with apparent molecular masses of 170 to 350 kDa. ETH assembled
      oligomers on a liposomal membrane consisting of phosphatidylcholine and
      cholesterol, but not on a membrane of phosphatidylcholine alone. Cholesterol
      could be replaced with diosgenin or ergosterol but not with 5alpha-cholestane-3
      one, suggesting that sterol is essential for the oligomerization. The treatment
      of carboxyfluorescein-encapsulated liposomes with ETH caused a rapid release of
      carboxyfluorescein into the medium. Because dextrin 20 (molecular mass, 900 Da)
      osmotically protected ETH-mediated hemolysis, this hemolysis is likely to be
      caused by pore formation on the membrane. The pore size(s) estimated from osmotic
      protection assays was in the range of 1.2 to 1.6 nm. The pore formed on a rabbit
      erythrocyte membrane was confirmed morphologically by electron microscopy. Thus,
      we provide evidence that ETH damages the target by the assembly of hemolysin
      oligomers and pore formation on the membrane.

PMID- 8757823
TI  - Selective killing of human monocytes and cytokine release provoked by
      sphingomyelinase (beta-toxin) of Staphylococcus aureus.
AB  - The best-known activity of Staphylococcus aureus sphingomyelinase C, alias beta
      toxin, is as a hemolysin that provokes hot-cold lysis of erythrocytes which
      contain substantial amounts of sphingomyelin in the plasma membrane. Sheep
      erythrocytes are most susceptible, and we found that one hemolytic unit,
      representing the toxin concentration that elicits 50% hemolysis of 2.5 X 10(8)
      erythrocytes per ml, corresponds to 0.05 enzyme units or to approximately 0.25
      microg of sphingomyelinase per ml. The cytotoxic action of beta-toxin on
      nucleated cells has not been described in any detail before, and the present
      investigation was undertaken to fill this information gap. We now identify beta
      toxin as a remarkably potent monocytocidal agent. At a concentration of 0.001
      U/ml, corresponding to approximately 5 ng/ml, beta-toxin killed over 50% of human
      monocytes (10(6) cells per ml) within 60 min. By contrast, 1 to 5 microg of beta
      toxin per ml had no cytocidal effects on human granulocytes, fibroblasts,
      lymphocytes, or erythrocytes. A selective monocytocidal action was also observed
      with sphingomyelinase C from Bacillus cereus and a Streptomyces sp., whereas
      phospholipase A2 and phospholipase D at 100 U/ml were without effect. Monocytes
      succumbing to the action of beta-toxin processed and released interleukin-1beta,
      soluble interleukin-6 receptor, and soluble CD14 into the supernatant. Thus,
      monocyte killing by beta-toxin is associated with cytokine-related events that
      are important for the initiation and progression of infectious disease. These
      findings uncover a potentially important role for sphingomyelinase as a
      determinant of microbial pathogenicity.

PMID- 8757824
TI  - Identification and characterization of the Yersinia enterocolitica gsrA gene,
      which protectively responds to intracellular stress induced by macrophage
      phagocytosis and to extracellular environmental stress.
AB  - Yersinia enterocolitica is able to resist the microbicidal mechanisms of
      macrophages and to grow within phagocytic cells. Some bacteria including Y.
      enterocolitica have been shown to respond to the hostile environment in
      macrophages by producing a set of stress proteins which are also induced by
      environmental stresses. To understand the role of stress proteins in
      intracellular survival of bacteria, we identified and cloned a Y. enterocolitica
      gene, called gsrA (global stress requirement). The gsrA gene was identified
      because its insertional inactivation by a transposon resulted in the inability of
      the organism to grow at an elevated temperature and to survive within macrophages
      after phagocytosis. The gsrA gene was sequenced and shown to encode a basic,
      49,500-Da protein. The GsrA protein shows significant amino acid sequence
      homology to the HtrA stress protein which was originally identified in
      Escherichia coli. Furthermore, the genetically defined Y. enterocolitica gsrA
      mutant was constructed and characterized. The insertional mutation of gsrA
      resulted in inhibition of growth at temperatures above 39 degrees C and greatly
      increased susceptibility to oxidative and osmotic stresses. The mutant
      additionally lost the ability to survive and replicate within macrophages. These
      results, taken together, indicate that the gsrA gene is an essential component of
      the protection mechanism employed by Y. enterocolitica, allowing it to respond to
      the intracellular stress in macrophages as well as extracellular environmental
      stress.

PMID- 8757825
TI  - Invasion of epithelial cells by Actinobacillus actinomycetemcomitans: a dynamic,
      multistep process.
AB  - The invasion process of Actinobacillus actinomycetemcomitans, a
      periodontopathogen, was studied with microscopy and viable quantitative assays
      using both KB and Madin-Darby canine kidney (MDCK) epithelial cells. Microscopy
      revealed that the events associated with the A. actinomycetemcomitans invasion
      process occurred rapidly. Scanning electron micrographs revealed A.
      actinomycetemcomitans associated with craters on the KB cell surface and others
      entering the KB cells through apertures with lip-like rims within 30 min of
      infection. Both transmission electron and immunofluorescence micrographs
      demonstrated that by this time some bacteria had, in fact, already entered,
      replicated, and exited host cells. Scanning electron micrographs revealed that
      infected KB cells exhibited fibrillar protrusions which contained bulges with the
      conformation of bacteria. Some protrusions formed intercellular connections
      between KB cells. Immunofluorescence micrographs revealed protrusions which
      harbored A. actinomycetemcomitans. The spread of internalized A.
      actinomycetemcomitans from one MDCK epithelial cell monolayer to another was
      demonstrated using a sandwich assay developed in our laboratory. Transcytosis of
      A. actinomycetemcomitans through polarized MDCK cells was also demonstrated. This
      study indicates that soon after entry of A. actinomycetemcomitans bacteria into
      epithelial cells, they undergo rapid multiplication and may subsequently be found
      in protrusions which sometimes extend between neighboring epithelial cells. The
      protrusions are thought to mediate the cell-to-cell spread of A.
      actinomycetemcomitans. Cell-to-cell spread may also occur by the endocytosis of
      A. actinomycetemcomitans bacteria which have been released into the medium via
      rudimentary protrusions which do not interconnect epithelial cells. The finding
      that the A. actinomycetemcomitans invasion process is so dynamic sheds
      significant new light on the interaction of this periodontopathogen with
      mammalian cells.

PMID- 8757826
TI  - Invasion of primary nasopharyngeal epithelial cells by Neisseria meningitidis is
      controlled by phase variation of multiple surface antigens.
AB  - We have investigated bacterial factors required for the entry of Neisseria
      meningitidis serogroup B into mucosal cells using a novel in vitro infection
      model of primary cultures of human nasopharyngeal epithelium. An invasive
      meningococcal phenotype was obtained after several cycles of selection for
      intracellular bacteria with gentamicin. Invasive bacteria differed from those in
      the initial inoculum in that they lacked a capsule and pili, exhibited a
      nonsialylated low-molecular-weight type of lipopolysaccharide (LPS), and produced
      a new 28-kDa opacity outer membrane protein. LPS revertants of the selected
      meningococci expressed a nonsialylated L3,(7,9) type of LPS and were also
      invasive, while after LPS sialylation bacterial entry was inhibited. Variants
      lacking the 28-kDa opacity protein were poorly invasive. Coexpression of the
      outer membrane protein Opc and the 28-kDa opacity protein strongly inhibited
      microbial invasion into the primary cultured nasopharyngeal cells. Conversely,
      meningococcal internalization by cells of various epithelia] cell lines was
      correlated with the expression of Opc rather than the 28-kDa opacity protein. Our
      data indicate that a concurrent phase switching of multiple phase-variable
      bacterial surface components may be a prerequisite for meningococcal invasion
      into nasopharyngeal epithelium and that meningococcal class 5 proteins (Opa and
      Opc) may promote tissue tropism.

PMID- 8757827
TI  - Mitogenic activities of amino acid substitution mutants of staphylococcal
      enterotoxin B in human and mouse lymphocyte cultures.
AB  - Site-directed mutagenesis has been used to introduce amino acid substitutions at
      specific residues of the staphylococcal enterotoxin B (SEB) gene cloned from
      Staphylococcus aureus 10-275. The mitogenic activities of these derivatives were
      determined in two assay systems: (i) mouse spleen cells and (ii) a mixture of
      human peripheral blood mononuclear cells and lymphocytes. Substitution of either
      His-12, His-32, His-121, His-166, Lys-152, or Gly-205 did not significantly alter
      the mitogenic activity from that of the wild-type toxin in either proliferation
      assay. Substitution of either residue Asn-23, Phe-44, or Cys-93 reduced the
      mitogenicity of SEB by a degree that depended upon the assay system used. Similar
      to the results reported by others measuring toxin activation of mouse lymphoid
      cells, we found that substitutions of these three residues of SEB caused at least
      800-fold reductions of mitogenic activity from that of the wild-type toxin. When
      tested for toxicity in vivo in D-galactosamine-treated mice, the reduced
      activities of these mutant toxins, however, were not as pronounced. In contrast,
      when tested in the human cell mitogenicity assay, these mutant toxins were
      active. Small alterations in activity (two- to fivefold reduction) were
      observable only at low concentrations. Our findings reveal the importance of
      using human lymphocytes in addition to the traditional mouse spleen cell assay
      when assessing biological activities of staphylococcal enterotoxins.

PMID- 8757828
TI  - Cytokine production by human epithelial and endothelial cells following exposure
      to oral viridans streptococci involves lectin interactions between bacteria and
      cell surface receptors.
AB  - In order to examine the possible implication of human epithelial and endothelial
      cells in the pathogenesis of various diseases associated with oral viridans
      streptococci, we tested the immunomodulatory effects of 11 representative strains
      of oral viridans streptococci on human epithelial KB cells and endothelial cells.
      We then examined the possible role of two major adhesins from oral viridans
      streptococci, protein I/II and rhamnose-glucose polymers (RGPs), in this process.
      In this study we demonstrate that oral viridans streptococci are potent
      stimulators of interleukin-8 (IL-8) production from KB cells and of IL-6 and IL-8
      production from endothelial cells. The ability of protein I/II and RGPs to
      contribute to these effects was then examined. Using biotinylated protein I/IIf
      and RGPs from Streptococcus mutans OMZ 175, we showed that these adhesins bind to
      KB and endothelial cells through specific interactions and that the binding of
      these molecules initiates the release of IL-8 from KB cells and of IL-6 and IL-8
      from endothelial cells. These results suggest that protein I/IIf and RGPs play an
      important role in the interactions between bacteria and KB and endothelial cells
      in that similar cytokine profiles are obtained when cells are stimulated with
      bacteria or surface components. We also provide evidence that protein I/IIf binds
      to and stimulates KB and endothelial cells through lectin interactions and that N
      acetyl neuraminic acid (NANA) and fucose present on cell surface glycoproteins
      may form the recognition site since binding and cytokine release can be inhibited
      by dispase and periodate treatment of cells and by NANA and fucose. These results
      demonstrate that oral viridans streptococci, probably by engaging two cell
      surface adhesins, exert immunomodulatory effects on human KB and endothelial
      cells.

PMID- 8757829
TI  - Iron uptake and iron-repressible polypeptides in Yersinia pestis.
AB  - Pigmented (Pgm+) cells of Yersinia pestis are virulent, are sensitive to
      pesticin, adsorb exogenous hemin at 26 degrees C (Hms+), produce iron-repressible
      outer membrane proteins, and grow at 37 degrees C in iron-deficient media. These
      traits are lost upon spontaneous deletion of a chromosomal 102-kb pgm locus (Pgm
      ). Here we demonstrate that an Hms+ but pesticin-resistant (Pst(r)) mutant
      acquired a 5-bp deletion in the pesticin receptor gene (psn) encoding IrpB to
      IrpD. Growth and assimilation of iron by Pgm- and Hms+ Pst(r) mutants were
      markedly inhibited by ferrous chelators at 37 degrees C; inhibition by ferric and
      ferrous chelators was less effective at 26 degrees C. Iron-deficient growth at 26
      degrees C induced iron-regulated outer membrane proteins of 34, 28.5, and 22.5
      kDa and periplasmic polypeptides of 33.5 and 30 kDa. These findings provide a
      basis for understanding the psn-driven system of iron uptake, indicate the
      existence of at least one additional 26 degrees C-dependent iron assimilation
      system, and define over 30 iron-repressible proteins in Y. pestis.

PMID- 8757830
TI  - Identification of surface-exposed B-cell epitopes on high molecular-weight
      adhesion proteins of nontypeable Haemophilus influenzae.
AB  - We previously reported that two surface-exposed high-molecular-weight proteins,
      HMW1 and HMW2, expressed by a prototypic strain of nontypeable Haemophilus
      influenzae (NTHI) mediate attachment to human epithelial cells. These proteins
      are members of a family of highly immunogenic proteins common to most nontypeable
      Haemophilus strains. We also reported that immunization with an HMW1-HMW2 mixture
      modified the course of disease in an animal model of otitis media, suggesting the
      potential usefulness of these proteins as NTHI vaccine components. Identification
      of surface-accessible B-cell epitopes could be important to efforts to develop
      recombinant or synthetic peptide vaccines based upon these high-molecular-weight
      proteins. Thus, the purpose of the present study was to identify surface
      accessible epitopes on the HMW1 and HMW2 proteins by using monoclonal antibodies
      (MAbs) and to determine the prevalence of these epitopes among the high-molecular
      weight proteins expressed by heterologous nontypeable Haemophilus strains. MAbs
      were generated by immunizing mice with high-molecular-weight proteins purified
      from prototype strains and were screened by immunoelectron microscopy (IEM) for
      the ability to recognize surface epitopes. Two MAbs, designated AD6 and 10C5,
      that recognized surface epitopes by IEM were recovered. In order to map the
      epitopes recognized by these two MAbs, we constructed a set of HMW1 and HMW2
      recombinant fusion proteins using the pGEMEX vectors and examined the reactivity
      of the MAbs with these fusion proteins. MAb AD6 recognized an epitope in both
      HMW1 and HMW2 which mapped to the last 75 amino acids at the carboxy termini of
      the two proteins. When examined for reactivity with heterologous strains, MAb AD6
      recognized high-molecular-weight proteins in 75% of 125 unrelated nontypeable
      Haemophilus strains and, in addition, reacted with three of three such strains
      when examined by IEM. MAb 10C5 recognized an epitope that mapped to a 155-amino
      acid segment near the carboxy terminus of HMW1. This epitope was adjacent to but
      distinct from the AD6 epitope and was absent from HMW2. The 10C5 epitope was
      expressed by 40% of the AD6 reactive strains. Identification of shared surface
      exposed epitopes on the high-molecular-weight adhesion proteins suggests the
      possibility of developing recombinant or synthetic peptide-based vaccines
      protective against disease caused by the majority of NTHI strains.

PMID- 8757831
TI  - Novel insights into the genetics, biochemistry, and immunocytochemistry of the 30
      kilodalton major extracellular protein of Mycobacterium tuberculosis.
AB  - The 30/32-kDa complex of major secretory proteins are among the most important
      and intensively studied proteins of Mycobacterium tuberculosis. The proteins have
      been demonstrated to be immunoprotective and to play a central role in the
      physiology of the mycobacterium. In this study, we present a series of novel
      insights into this key protein complex arising out of a combination of genetic,
      biochemical, and immunocytochemical analyses. Our genetic analyses (i) indicate
      that the genes are arranged as separate transcription units, (ii) demonstrate
      that the mature 30-kDa protein of M. tuberculosis differs from the corresponding
      30-kDa proteins of two strains of Mycobacterium bovis BCG by only 1 and 5 amino
      acids, (iii) suggest that expression of the proteins is regulated at the
      transcriptional level, and (iv) map the transcriptional start site of the 30-kDa
      protein gene. Our biochemical analyses provide evidence that (i) the 30-kDa
      protein and the two 32-kDa proteins (i.e., 32A and 32B) are secreted at a ratio
      of approximately 3:2:1, respectively, (ii) the proteins exist as monomers, (iii)
      the proteins are not posttranslationally modified by the addition of
      carbohydrates and lipids, (iv) the 30-kDa and 32A proteins contain one disulfide
      bridge, and (v) high-level expression and leader peptide processing are
      achievable in Escherichia coli. Our immunocytochemical analyses demonstrate that
      the 30/32-kDa complex is expressed in human monocytes and that the proteins are
      localized to the phagosomal space and the mycobacterial cell wall. These analyses
      fill important gaps in our knowledge of this critical protein complex of M.
      tuberculosis and, at the same time, raise new and fundamental questions regarding
      regulatory mechanisms that control coordinate expression of the proteins at a
      fixed ratio.

PMID- 8757832
TI  - Localization of a yeast-phase-specific gene product to the cell wall in
      Histoplasma capsulatum.
AB  - A yeast-phase-specific gene, yps-3, has been identified in the virulent
      Histoplasma capsulatum strain, G217B. Although DNA sequencing of the genomic yps
      3 gene from G217B failed to detect homologies with known proteins, the 5' end of
      a yps-3 cDNA contained a consensus signal sequence. A 519-bp fragment of the cDNA
      containing the translational stop codon was linker modified and inserted into the
      bacterial expression vector, pATH 1. Escherichia coli extracts containing the
      pATH 1 vector alone expressed a major 34-kDa TrpE polypeptide following induction
      with indoleacrylic acid, while the pATH 1/yps-3 construct produced a predominant
      54-kDa TrpE/yps-3 fusion protein. Polyclonal rabbit sera directed against G217B
      reacted exclusively with the 54-kDa fusion protein in Western blots
      (immunoblots); serum samples from three patients with acute pulmonary or
      disseminated histoplasmosis were also positive. To localize the yps-3 protein
      within G217B, a monoclonal antibody (MAb 7.1) which recognized the yps-3 portion
      of the fusion protein was generated. A 17.4-kDa protein was detected with MAb 7.1
      in Western blots prepared from cell wall fractions of G217B; cytoplasmic
      fractions were unreactive. No yps-3 antigen was detected in either fraction of
      the Downs strain, which fails to express the yps-3 gene. MAb 7.1 also detected a
      17.4-kDa antigen in ethanol-precipitated culture supernatants derived from G217B.
      These findings localize the yps-3 gene product to the cell wall and culture
      supernatants, where the protein may influence the phase transition or the
      maintenance of the yeast state.

PMID- 8757833
TI  - Engineered deltaguaB-A deltavirG Shigella flexneri 2a strain CVD 1205:
      construction, safety, immunogenicity, and potential efficacy as a mucosal
      vaccine.
AB  - Shigella flexneri 2a strain CVD 1204, which was constructed by introducing a
      specific, in-frame deletion mutation in the guaB-A operon, was compared with
      deltaaroA strain CVD 1201. CVD 1204 was less invasive for HeLa cells than CVD
      1201, whereas following invasion, the abilities of the two mutants to proliferate
      intracellularly were similarly impaired. The reduction in invasiveness was
      independent of the guanine auxotrophic phenotype and fully recovered when the
      chromosomal deletion mutation in CVD 1204 was repaired. Following inoculation of
      the conjunctival sac of guinea pigs (Sereny test) at high doses (10(9) CFU per
      eye), both strains evoked minimal, short- lived conjunctival inflammation, which
      was significantly milder with strain CVD 1204. Double mutant deltaguaB-A
      deltavirG (also called icsA) strain CVD 1205 induced, after a single intranasal
      dose, high mucosal immunoglobulin A antilipopolysaccharide titers, which were
      significantly boosted further following a second dose of vaccine given 14 days
      later. Upon Sereny test challenge with wild-type S. flexneri 2a, CVD 1205
      vaccinated animals were significantly protected against keratoconjunctivitis
      (zero of eight vaccinees versus five of seven controls, P = 0.03; vaccine
      efficacy, 100%). CVD 1205 is an attractive candidate for human clinical trials.

PMID- 8757835
TI  - Experimental immunization of rats with a Streptococcus mutans 59-kilodalton
      glucan-binding protein protects against dental caries.
AB  - Glucan-binding proteins (GBPs) are theoretically important in the molecular
      pathogenesis of dental caries caused by Streptococcus mutans. The present study
      evaluated the ability of antibody induced by the S. mutans 59-kDa GBP (GBP59) to
      affect dental caries caused by experimental infection with S. mutans in a rodent
      model. Groups of 20-day-old rats were injected twice at 9-day intervals
      subcutaneously in the salivary gland vicinity with GBP59, glucosyltransferase
      (GTF), or phosphate-buffered saline (sham injection), each incorporated in an
      adjuvant. Two weeks after the second injection, GBP59- and GTF-injected rats
      contained significant levels of salivary immunoglobulin A and serum
      immunoglobulin G antibody to the respective injected antigens. However, cross
      reacting antibody to S. mutans GTF or GBP59 was not induced by the respective
      antigen. Rats were then orally infected with S. mutans. After 71 days of
      infection, GBP59- and GTF-injected groups had smaller numbers of S. mutans on
      their molar surfaces, compared with the sham-injected infected group. Total,
      sulcal, and smooth-surface molar caries in the GBP59- and GTF-immunized S. mutans
      infected groups were each significantly lower (P < or = 0.003) than the
      respective measures of caries in the sham injected infected group. The results of
      this investigation demonstrate that immunization with S. mutans GBP59 induces an
      immune response in rats that can interfere with the accumulation of S. mutans and
      can reduce the level of dental caries caused by this cariogenic streptococcus.
      Furthermore, the protective immunity induced by either GBP59 or GTF appears to
      result from antibodies to independent epitopes since these two S. mutans
      components do not have a close antigenic relationship.

PMID- 8757834
TI  - Induction of cytokine granulocyte-macrophage colony-stimulating factor and
      chemokine macrophage inflammatory protein 2 mRNAs in macrophages by Legionella
      pneumophila or Salmonella typhimurium attachment requires different ligand
      receptor systems.
AB  - The attachment of bacteria to macrophages is mediated by different ligands and
      receptors and induces various intracellular molecular responses. In the present
      study, induction of cytokines and chemokines, especially granulocyte-macrophage
      colony-stimulating factor (GM-CSF) and macrophage inflammatory protein 2 (MIP-2),
      was examined, following bacterial attachment, with regard to the ligand-receptor
      systems involved. Attachment of Legionella pneumophila or Salmonella typhimurium
      to cultured mouse peritoneal macrophages increased the steady-state levels of
      cellular mRNAs for the cytokines interleukin 1beta (IL-1beta), IL-6, and GM-CSF
      as well as the chemokines MIP-1beta, MIP-2, and KC. However, when macrophages
      were treated with alpha-methyl-D-mannoside (alphaMM), a competitor of
      glycopeptide ligands, induction of cytokine mRNAs was inhibited, but the levels
      of chemokine mRNAs were not. Pretreatment of the bacteria with fresh mouse serum
      enhanced the level of GM-CSF mRNA but not the level of MIP-2 mRNA. In addition,
      serum treatment reduced the inhibitory effect of alphaMM on GM-CSF mRNA. These
      results indicate that bacterial attachment increases the steady-state levels of
      the cytokine and chemokine mRNAs tested by at least two distinct receptor-ligand
      systems, namely, one linked to cytokine induction and involving mannose or other
      sugar residues and the other linked to chemokine induction and relatively alphaMM
      insensitive. Furthermore, opsonization with serum engages other pathways in the
      cytokine response which are relatively independent of the alphaMM-sensitive
      system. Regarding bacterial surface ligands involved in cytokine mRNA induction,
      evidence is presented that the flagellum may be important in stimulating cytokine
      GM-CSF message but not chemokine MIP-2 message. Analysis of cytokine GM-CSF and
      chemokine MIP-2 signaling pathways with protein kinase inhibitors revealed the
      involvement of calmodulin and myosin light-chain kinase in GM-CSF but not MIP-2
      mRNA induction, adding further evidence that several distinct receptor systems
      are engaged during the process of bacterial attachment and induction of cytokines
      and chemokines, such as GM-CSF and MIP-2, respectively.

PMID- 8757836
TI  - Counterprotective effect of erythrocytes in experimental bacterial peritonitis is
      due to scavenging of nitric oxide and reactive oxygen intermediates.
AB  - Erythrocytes (RBC) in the peritoneal cavity significantly increase the lethality
      of bacterial peritonitis. The lethality is known to be associated with, and
      perhaps due to, increased bacterial counts in the peritoneal cavity. The
      mechanism is unknown. In this study, we investigated the hypothesis that RBC
      scavenge reactive oxygen intermediates (ROI) and nitric oxide (NO), so that the
      counterprotective effect is due to a loss of the microbiostatic activity of both
      ROI and NO. To study this effect, rats were subjected to a peritoneal inoculation
      of live Escherichia coli without RBC (nonlethal dose) or with RBC (lethal dose).
      The adjuvant effect of RBC was not modified by NG-monomethyl-L-arginine (NMA, an
      NO synthase inhibitor), superoxide dismutase, catalase, mannitol, or a
      combination of these agents. Furthermore, the increased number of bacteria in the
      peritoneal cavity in the presence of RBC was unaffected by these treatments. The
      administration of NMA with bacteria alone (no RBC) converted a nonlethal model
      into a lethal one associated with higher intraperitoneal bacterial counts. A
      similar effect was seen with superoxide dismutase and catalase but not with
      mannitol. During bacterial peritonitis in the absence of RBC, superoxide and NO
      formation (determined by the total nitrite plus nitrate formed) was detected in
      the ascites and inducible NO synthase mRNA expression was present in the
      peritoneal cells. In the absence of RBC, superoxide was detected and oxidation of
      dihydrorhodamine to rhodamine was observed, indicating that peroxynitrite was
      produced. Both were blocked by the inclusion of RBC. Preinjection with a low
      inoculum of killed bacteria protected the rats from a subsequent lethal
      peritoneal bacterial challenge; this effect was reversed by scavenging ROI and
      NO. The protective effect of killed bacterial pretreatment was lost when RBC were
      placed in the peritoneal cavity. In vitro bactericidal activity of NO- and ROI
      generating macrophages was also inhibited by RBC or by inhibiting ROI and NO
      formation. Taken together, these data are consistent with the hypothesis that RBC
      can impair bacterial clearance by removing both NO and ROI, suggesting that NO in
      combination with superoxide may be important to the antimicrobial defenses of the
      peritoneal cavity.

PMID- 8757837
TI  - Escherichia coli hemolysin mutants with altered target cell specificity.
AB  - In order to understand the functional significance of HlyC-dependent acylation of
      the Escherichia coli hemolysin structural protein (HlyA), random as well as site
      directed substitutions at the known regions of modification, i.e., those at
      lysine residues at amino acid positions 563 and 689 (HlyAK563 and HlyAK689,
      respectively), were isolated. Sixteen random hlyA mutations were identified on
      the basis of a screen for loss of immunoreactivity to the hemolysin-neutralizing
      D12 monoclonal antibody that reacts to only HlyC-activated HlyA. These
      substitutions occurred at the region from HlyAE684 to HlyAY696. A recombinant
      glutathione S-transferase-hemolysin gene fusion encoding glutathione S
      transferase-HlyAS608-T725 residues reacts with monoclonal antibody when HlyC is
      coexpressed with the fusion protein. Therefore, at most only 12% of the total
      HlyA primary sequence is needed for HlyC-facilitated acylation at the HlyAK689
      position, and this modification can occur in the absence of the proximal HlyAK563
      acylation site. The cytolytic activities of these HlyA mutants against sheep
      erythrocytes and bovine and human lymphocyte cell lines (BL-3 and Raji cells,
      respectively) were analyzed. HlyAK563 and HlyAK689 substitutions displayed
      various degrees of loss of cytotoxicity that depended on the particular amino
      acid replacement. An HlyAK563C variant retained greater than 59 and 21% of its BL
      3-lytic and erythrolytic activities, respectively, but was nearly inactive
      against Raji cells. An HlyA mutant with a K-to-E substitution at amino acid 689
      (HlyAK689E) was essentially inactive against all three cell types, whereas an
      HlyAK689R substitution had a pattern of activity similar to that of the HlyAK563C
      mutant. Preceding the two in vitro acylated HlyA lysines are glycines that appear
      to be the only amino acids conserved in alignments of these regions among the RTX
      toxins. Remarkably, considering the retention of cytotoxic activity by some
      HlYAK689 mutants, each of three different substitutions at the HlyAG688 position
      was relatively inactive against all three cell types tested. This suggests that
      HlyAG688 plays a significant structural role in cytotoxic activity apart from its
      possible participation in an HlyC activation process which presumably requires
      recognition of pro-HlyA structures. The related RTX toxin, the Pasteurella
      haemolytica leukotoxin structural protein (LktA), can be activated in an E. coli
      recombinant background by HlyC. In amino acid sequence alignments, LktAK554 is
      equivalent to the HlyAK563 position but it has an asparagine (LktAN684) at the
      homologous HlyAK689 site. An LktAN684K substitution possesses wild-type
      leukotoxin activity against BL-3 cells and does not acquire hemolytic or Raji
      cell cytotoxic activity. Surprisingly, both LktAK554C and LktAK554T substitutions
      retain considerable BL-3 cytotoxicity (45 and 49%, respectively), indicating that
      there may be additional lysines within LktA that the HlyC activation mechanism is
      capable of acylating. Based on these results and a comparison of amino acid
      sequence alignments of 12 RTX toxins, a putative consensus structure of the RTX
      residues necessary for HlyC activation is hypothesized.

PMID- 8757838
TI  - Intact immune defenses are required for mice to resist the ts-4 vaccine strain of
      Toxoplasma gondii.
AB  - The ts-4 strain of Toxoplasma gondii is a temperature-sensitive mutant that fails
      to grow at 40 degrees C in vitro. Unlike mildly virulent cyst-forming strains,
      which can cause fatal chronic infections in certain mouse strains, ts-4 has been
      widely used to vaccinate mice against virulent T. gondii and is a valuable tool
      with which to investigate mechanisms of acquired resistance to this parasite. In
      this report, the basis for the avirulence of ts-4 is analyzed. It is shown that
      ts-4 is able to persist long-term in vivo in mildly immunocompromised mice, which
      rules out an intrinsic growth defect as a reason for avirulence. ts-4 does not
      induce body temperatures in mice as high as that needed to kill it in vitro.
      Moreover, the mild fevers elicited in resistant B6 mice are also seen in
      susceptible C57BL/6 scid/scid mice. However, ts-4 elicits strong preimmune
      defenses, dependent on gamma interferon, which are needed by mice to survive
      acute infection. Furthermore, CD4+ and CD8+ T-cell-dependent acquired immunity is
      essential for long-term survival of ts-4-infected mice.

PMID- 8757839
TI  - Intermedilysin, a novel cytotoxin specific for human cells secreted by
      Streptococcus intermedius UNS46 isolated from a human liver abscess.
AB  - A novel cytotoxin (intermedilysin) specific for human cells was identified as a
      cytolytic factor of Streptococcus intermedius UNS46 isolated from a human liver
      abscess. Intermedilysin caused human cell death with membrane blebs.
      Intermedilysin was purified from UNS46 culture medium by means of gel filtration
      and hydrophobic chromatography. The purified toxin was resolved into major and
      minor bands of 54 and 53 kDa, respectively, by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. These proteins reacted with an antibody
      against intermedilysin. Five internal peptide fragments of intermedilysin were
      sequenced and found to have 42 to 71% homology with the thiol-activated cytotoxin
      pneumolysin. However, the action of intermedilysin differed from that of thiol
      activated cytotoxins, especially in terms of a lack of activation by
      dithiothreitol and resistance to treatments with N-ethylmaleimide and 5,5'-dithio
      bis-(2-nitrobenzoic acid), although cholesterol inhibited the toxin activity.
      Intermedilysin was potently hemolytic on human erythrocytes but was 100-fold less
      effective on chimpanzee and cynomolgus monkey erythrocytes. Intermedilysin was
      not hemolytic in nine other animal species tested. Since human erythrocytes
      treated with trypsin were far less sensitive to intermedilysin than were the
      intact cells, a cell membrane protein(s) may participate in the intermedilysin
      action. These data demonstrated that intermedilysin is distinguishable from all
      known bacterial cytolysins.

PMID- 8757840
TI  - Purification and characterization of an extracellular secretogenic non-membrane
      damaging cytotoxin produced by clinical strains of Vibrio cholerae non-O1.
AB  - Some clinical strains of Vibrio cholerae non-O1 produce an extracellular factor
      that evokes a rapid and dramatic cytotoxic response which manifests as cell
      rounding of Chinese hamster ovary (CHO) and HeLa cells without accompanying
      membrane damage. This study was performed to establish the identity of the non
      membrane-damaging cytotoxin (NMDCY), which was not inhibited by antitoxins
      against cholera toxin, heat-labile toxin of enterotoxigenic Escherichia coli, El
      Tor hemolysin, Shiga-like toxin I, and Shiga-like toxin II, indicating that NMDCY
      did not bear an apparent immunological relationship with the above toxins and
      hemolysin. Brain heart infusion broth and AKI medium supported the maximal
      production of NMDCY; culture supernatant of AKI medium was found to be free of
      hemolysin activity, whereas in brain heart infusion broth hemolysin was
      coproduced with NMDCY. Maximal production of NMDCY in AKI medium was observed at
      37 degrees C under shaking conditions with the pH of the medium adjusted to 8.5.
      NMDCY was purified to homogeneity by a three-step purification procedure which
      increased the specific activity of the cytotoxin by 1.7 X 10(5)-fold. The
      denatured molecular weight of the purified toxin was 35,000, and the cytotoxin
      was heat labile and sensitive to trypsin. Purification of the cytotoxin revealed
      an enterotoxic activity as reflected by its ability to accumulate fluid in the
      rabbit ileal loop. Both the cytotoxic and enterotoxic activities of NMDCY could
      be inhibited or neutralized by antiserum raised against purified cytotoxin but
      not by preimmune serum. Immunodiffusion test between purified NMDCY and antiserum
      gave a single well-defined precipitin band which showed reactions of complete
      identity, while, in an immunoblot assay, a well-defined single band was observed
      in the 35-kDa region. Our results indicate that the cytotoxic and enterotoxic
      activities expressed by NMDCY appear to contribute to the pathogenesis of the
      disease associated with V. cholerae non-O1 strains which produce this cytotoxin.

PMID- 8757841
TI  - Brucella abortus as a potential vaccine candidate: induction of interleukin-12
      secretion and enhanced B7.1 and B7.2 and intercellular adhesion molecule 1
      surface expression in elutriated human monocytes stimulated by heat-inactivated
      B. abortus.
AB  - Development of a vaccine which is capable of generating a strong cellular immune
      response associated with gamma interferon (IFN-gamma) production and cytotoxic T
      cell development requires that the immunogen be capable of inducing the secretion
      of interleukin-12 (IL-12), which is a pivotal factor for the differentiation of
      Th1 or Tc1 cells. We have previously shown that the heat-inactivated gram
      negative bacterium Brucella abortus can induce IFN-gamma secretion by T cells. In
      the present study, we demonstrate that B. abortus and lipopolysaccharide (LPS)
      from B. abortus can induce IL-12 p40 mRNA expression and protein secretion by
      human elutriated monocytes (99% pure). p40 mRNA was detected within 4 h, and p40
      protein could be measured at 24 h. This induction was abrogated by anti-CD14
      monoclonal antibody, suggesting that monocytes recognize B. abortus via their
      receptor for LPS. The biological activity of IL-12 secreted by B. abortus
      stimulated monocytes was demonstrated by its ability to upregulate IFN-gamma mRNA
      expression in T cells separated from monocytes and B. abortus by a transwell
      membrane. The B. abortus-induced IL-12 also enhanced NK cytolytic activity
      against K562 target cells. B. abortus was shown to rapidly increase the
      expression of the costimulatory molecules B7.1 and B7.2 and intercellular
      adhesion molecule 1 on human monocytes. Together, these data indicate that B.
      abortus can directly activate human monocytes and provide the cytokine milieu
      which would direct the immune response towards Th1-Tc1 differentiation.

PMID- 8757842
TI  - Escherichia coli cellulitis in broiler chickens: clonal relationships among
      strains and analysis of virulence-associated factors of isolates from diseased
      birds.
AB  - Thirty-nine Escherichia coli isolates from broiler chickens with cellulitis were
      serotyped and analyzed for clonal relationships by multilocus enzyme
      electrophoresis. The isolates were further characterized with respect to
      hemagglutination (HA); serum resistance; antibiotic susceptibility; production of
      aerobactin, colicin V, and hemolysin; expression of K1 or K5 capsule; sensitivity
      to cloacin DF13 after treatment with diphenylamine; expression of iron-regulated
      outer membrane proteins; and virulence in 1-day-old chickens. In addition, the
      isolates were examined for the presence of DNA sequences related to F1A (fim) and
      P (pap) fimbriae, aerobactin synthesis (iuc) and transport (iut), hemolysin
      operon hly, and TraT lipoprotein-induced serum resistance (traT). Only 38.4% of
      the isolates were typeable with standard O antisera, and of these, serogroups O25
      and O78 were the most frequently observed. Multilocus enzyme electrophoresis,
      based on 20 enzymes, resolved 17 electrophoretic types, forming seven clusters.
      Isolates from four of these clusters fell into E. coli clone complexes that have
      been previously reported to be commonly associated with avian colibacillosis. All
      isolates expressed two to five iron-regulated outer membrane proteins, were
      resistant to serum and cloacin DF13, and possessed DNA sequences homologous to
      fim and iuc/iut. Most isolates (72%) were positive for traT, and a majority
      produced colicin V and aerobactin (92 and 82%, respectively). Assays for the
      presence of fim and pap DNA sequences, for HA, and for virulence gave variable
      results but suggest that cellulitis isolates may express F1A and/or other mannose
      resistant HA fimbriae different from P and may be virulent in 1-day-old chickens.
      Our results support the hypothesis that cellulitis in broilers in many cases is
      caused by E. coli clones identical to other pathogenic avian E. coli strains.
      Certain clones may be specific to cellulitis, because 25% of the isolates tested
      belong to clusters not related to known clone complexes.

PMID- 8757843
TI  - Peroxynitrite contributes to the candidacidal activity of nitric oxide-producing
      macrophages.
AB  - Nitric oxide (NO) is associated with functions as diverse as peristalsis, blood
      flow, neuroendosecretion, visual transduction, smooth muscle relaxation, and
      microbial killing (H. H. W. H. Schmidt and V. Walter, Cell 78:919-925, 1994).
      Despite the well-established role of NO in macrophage candidacidal activity (E.
      Cenci, L. Romani, A. Mancacci, R. Spaccapelo, E. Schiaffella, P. Puccetti, and F.
      Bistoni, Eur. J. Immunol. 23:1034-1038, 1993; J. Jones-Carson, A. Vazquez-Torres,
      H. Van der Heide, R. D. Wagner, T. Warner, and E. Balish, Nature Med. 1:552-557,
      1995; and A. Vazquez-Torres, J. Jones-Carson, T. Warner, and E. Balish, J.
      Infect. Dis. 172:192-198, 1995), NO is not directly candidacidal for Candida
      albicans (A. Vazquez-Torres, J. Jones-Carson, and E. Balish, Infect. Immun.
      63:1142-1144, 1995). Because macrophages can produce both NO and superoxide anion
      (02-), we postulated that peroxynitrite (ONOO-), a product of the dilution
      limited reaction of NO and O2-, is the candidacidal molecule of activated
      macrophages. We now report that ONOO-, in addition to being candidacidal in
      vitro, is responsible for the candidacidal activity of NO-producing macrophages.
      ONOO- synthesis by NO-producing macrophages was triggered by two independent
      mechanisms: one was nonopsonic and dependent on fungal cell wall glucan moieties,
      and the other was dependent on opsonic antibodies. As we have demonstrated for
      the pathogenic fungus C. albicans, ONOO- may also be the molecule that enables
      macrophages to kill other microbes that are resistant to both O2- and NO.

PMID- 8757844
TI  - Cloning of a DNA fragment encoding a heme-repressible hemoglobin-binding outer
      membrane protein from Haemophilus influenzae.
AB  - Haemophilus influenzae is able to use hemoglobin as a sole source of heme, and
      heme-repressible hemoglobin binding to the cell surface has been demonstrated.
      Using an affinity purification methodology, a hemoglobin-binding protein of
      approximately 120 kDa was isolated from H. influenzae type b strain HI689 grown
      in heme-restricted but not in heme-replete conditions. The isolated protein was
      subjected to N-terminal amino acid sequencing, and the derived amino acid
      sequence was used to design corresponding oligonucleotides. The oligonucleotides
      were used to probe a Southern blot of EcoRI-digested HI689 genomic DNA. A
      hybridizing band of approximately 4.2 kb was successfully cloned into pUC19.
      Using a 1.9-kb internal BglII fragment of the 4.2-kb clone as a probe,
      hybridization was seen in both typeable and nontypeable H. influenzae but not in
      other bacterial species tested. Following partial nucleotide sequencing of the
      4.2-kb insert, a putative open reading frame was subcloned into an expression
      vector. The host Escherichia coli strain in which the cloned fragment was
      expressed bound biotinylated human hemoglobin, whereas binding of hemoglobin was
      not detected in E. coli with the vector alone. In conclusion, we hypothesize that
      the DNA fragment encoding an approximately 120-kDa heme-repressible hemoglobin
      binding protein mediates one step in the acquisition of hemoglobin by H.
      influenzae in vivo.

PMID- 8757845
TI  - Influence of agr on fibrinogen binding in Staphylococcus aureus Newman.
AB  - The ability of Staphylococcus aureus to bind fibrinogen is believed to be
      important in promoting bacterial adherence to both intravascular catheters and
      host tissues during infection. We investigated the influence of the global
      regulator agr on the fibrinogen binding capacity and its relationship to the
      expression of coagulase (encoded by coa) and clumping factor (encoded by clfA) in
      strain Newman. Strains were obtained by transducing site-specific mutations of
      clfA, coa, and agr into strain Newman to obtain single, double, and triple
      mutants of the respective genes. As expected, the clfA mutant bound less soluble
      125I-labeled fibrinogen than the corresponding coa mutant in agr+ strains;
      however, with agr mutant strains, the upregulation in fibrinogen binding capacity
      correlated mostly with the increased expression and transcription of coagulase as
      shown by Western (immunoblot) and Northern (RNA) blot analysis. In particular,
      the coa agr double mutant resulted in a significant reduction in fibrinogen
      binding compared with that of the agr mutant. The contribution of clfA to
      fibrinogen binding in agr-negative strains was less than that of coa (32,740 +/-
      1,189 versus 18,141 +/- 334 and 38,919 +/- 1,021 cpm for clfA agr, coa agr, and
      the single agr mutant, respectively). Thus, coagulase is a major binding protein
      for soluble fibrinogen in the agr-negative background. In in vitro microtiter and
      catheter adherence assays with solid-phase fibrinogen, clumping factor, but not
      coagulase, plays a major role in binding to immobilized fibrinogen. coa
      transcription was negatively modulated by agr and occurred mainly during the
      exponential growth phase. In contrast, clfA transcription was agr independent and
      was strongest during the postexponential phase. Although an agr coa clfA triple
      mutant bound less soluble fibrinogen than the agr coa double mutant (8,504 +/-
      831 versus 18,141 +/- 334 cpm), significant residual fibrinogen binding capacity
      remained in the triple mutant, thus suggesting an additional fibrinogen binding
      component. By using direct ligand affinity blotting with 125I-fibrinogen, we
      could identify coagulase and an additional unidentified 52-kDa protein as a
      fibrinogen binding component in cell extracts. This band was absent in the
      extract of the coa clfA double mutant.

PMID- 8757846
TI  - Neurotoxicity of glia activated by gram-positive bacterial products depends on
      nitric oxide production.
AB  - The present study examined the mechanism by which bacterial cell walls from two
      gram-positive meningeal pathogens, Streptococcus pneumoniae and the group B
      streptococcus, induced neuronal injury in primary cultures of rat brain cells.
      Cell walls from both organisms produced cellular injury to similar degrees in
      pure astrocyte cultures but not in pure neuronal cultures. Cell walls also
      induced nitric oxide production in cultures of astrocytes or microglia. When
      neurons were cultured together with astrocytes or microglia, the cell walls of
      both organisms became toxic to neurons. L-NAME, a nitric oxide synthase
      inhibitor, protected neurons from cell wall-induced toxicity in mixed cultures
      with glia, as did dexamethasone. In contrast, an excitatory amino acid antagonist
      (MK801) had no effect. Low concentrations of cell walls from either gram-positive
      pathogen added together with the excitatory amino acid glutamate resulted in
      synergistic neurotoxicity that was inhibited by L-NAME. The induction of nitric
      oxide production and neurotoxicity by cell walls was independent of the presence
      of serum, whereas endotoxin exhibited these effects only in the presence of
      serum. We conclude that gram-positive cell walls can cause toxicity in neurons by
      inducing the production of nitric oxide in astrocytes and microglia.

PMID- 8757847
TI  - Characterization of elastase-deficient clinical isolates of Pseudomonas
      aeruginosa.
AB  - Elastase production in Pseudomonas aeruginosa is regulated by the lasR, lasI,
      rhlR, and rhlI genes. Recently, we have analyzed several clinical isolates of P.
      aeruginosa for the production of elastase and other extracellular virulence
      factors. Four of these isolates (CIT1, CIW5, CIW7, and CIW8) produced no
      elastolytic activity. We have characterized these isolates with respect to their
      elastase-deficient phenotype. Elastase was detected by immunoblotting experiments
      using elastase-specific antiserum. We also determined the presence of IasB and
      IasR mRNAs by Northern (RNA) blot hybridization experiments using lasB and lasR
      internal probes, respectively. None of the four elastase-deficient strains
      produced either the elastase protein or the lasB mRNA. Complementation
      experiments (using plasmids carrying either the lasB or the lasR gene) were
      conducted to determine if the isolates carry defective lasB or lasR genes. The
      presence of either a lasB or a lasR plasmid in CIW7 and CIW8 resulted in the
      production of very low levels of elastase and lasB mRNA. Neither elastase nor
      lasB mRNA was detected in CIT1 and CIW5 carrying the lasB plasmid. The presence
      of the lasR plasmid in CIT1 and CIW5 resulted in the production of lasB mRNA and
      elastase protein in CIW5 only. All elastase-deficient strains produced detectable
      levels of lasR mRNA which were enhanced in the presence of the lasR plasmid. The
      Pseudomonas autoinducer (which is encoded by lasI) was also produced by all
      strains. CIT1 produced both hemolysin and alkaline protease but was defective in
      pyocyanin production. These results suggest that (i) CIT1 may contain a defect in
      a lasB-regulatory gene, (ii) CIW5 carries a defect within lasR, and (iii) the
      defect in isolates CIW7 and CIW8 affects the efficiency of lasB transcription.

PMID- 8757848
TI  - Cloning, sequencing, expression, and protective capacity of the oma87 gene
      encoding the Pasteurella multocida 87-kilodalton outer membrane antigen.
AB  - Membrane proteins of Pasteurella multocida have been shown previously to elicit
      protective immunity. We have identified an 87-kDa outer membrane antigen, Oma87,
      which is present in all 16 serotypes of P. multocida. The gene encoding this
      protein was cloned and sequenced and found to have significant similarity to the
      D15 protective surface antigen of Haemophilus influenzae. Oma87 was localized to
      the outer membrane of the cell, and proteinase K treatment suggested that the
      protein is surface exposed. Native and recombinant Oma87 were strongly
      immunostained by convalescent-phase antiserum, indicating that the protein is
      expressed in vivo. Specific Oma87 antiserum protected mice against homologous,
      lethal P. multocida challenge. These results suggest that Oma87 is a protective
      outer membrane antigen of P. multocida.

PMID- 8757849
TI  - Immune response in mice following immunization with DNA encoding fragment C of
      tetanus toxin.
AB  - Tetanus toxin is a potent neurotoxin synthesized by Clostridium tetani.
      Immunization with fragment C protein, the nontoxic C-terminal domain of tetanus
      toxin, will protect mice against lethal challenge with tetanus toxin. A synthetic
      gene encoding fragment C (tetC) had previously been shown to express high levels
      of fragment C in Saccharomyces cerevisiae. A plasmid, pcDNA3/tetC, which encodes
      the synthetic tetC gene expressed under the control of the human cytomegalovirus
      major intermediate-early promoter/enhancer region, was constructed. Expression of
      fragment C was observed in eukaryotic cells growing in vitro following
      transfection with pcDNA3/tetC. The immune response induced by intramuscular
      immunization with pure pcDNA3/tetC DNA was evaluated in a murine model. Anti
      fragment C serum immunoglobulin and proliferative responses in splenocytes were
      observed in BALB/c mice following two immunizations with pcDNA3/tetC. The major
      immunoglobulin G subclass that recognized fragment C was immunoglobulin G2a, and
      the stimulated splenocytes secreted high levels of gamma interferon. Immunity to
      tetanus is dependent on the presence of neutralizing serum antibodies against
      tetanus toxin. Sufficient anti-fragment C serum immunoglobulins were induced by
      DNA-mediated immunization to protect mice against lethal challenge with tetanus
      toxin.

PMID- 8757850
TI  - Target organs of infection in guinea pigs with acquired congenital syphilis.
AB  - The target organs of infection in guinea pigs with asymptomatic acquired or
      congenital syphilis were identified by PCR and in some cases by rabbit
      infectivity test (RIT). The prevalence of Treponema pallidum DNA was examined in
      the following seven organs: the inguinal and mesenteric lymph nodes, spleen,
      liver, kidney, heart, and brain. Test samples consisted of 95 organs from two
      genetically different strains of female guinea pigs (C4-deficient and Albany)
      with different susceptibilities to cutaneous infection by T. pallidum and 195
      organs from their asymptomatic offspring. Twenty organs from dams of both strains
      injected with heat-killed T. pallidum and 19 organs from their progeny served as
      negative controls. The infections of mothers and neonates were documented by PCR,
      RIT, and serology. Though any of the organs tested could be infected, there was a
      spirochetal predilection for some anatomical locations, such as the lymph nodes,
      heart, and brain, regardless of the strain, route of maternal infection, and age.
      None of the 49 organs collected from control animals were positive by PCR. In
      infected C4-deficient dams, one to four organs were positive by PCR, whereas the
      organs of 7 of their 27 (25%) asymptomatic offspring were treponemal DNA
      negative, despite evidence of immunoglobulin M treponemal antibodies. Comparative
      analysis done by both PCR and RIT on a limited number of samples showed 90%
      agreement between results. An examination of multiple samples obtained from
      single organs demonstrated that even within 24 h of spirochetemia, when most
      organs appeared to be infected, not all samples from an individual organ were
      positive by PCR. A specific immunological response in guinea pigs with congenital
      syphilis was a more consistent parameter of vertical transmission than was an
      analysis of T. pallidum DNA.

PMID- 8757851
TI  - Outer surface lipoproteins of Borrelia burgdorferi activate vascular endothelium
      in vitro.
AB  - Previously, we reported that activation of vascular endothelium by the Lyme
      disease pathogen Borrelia burgdorferi results in enhanced expression of
      endothelial cell adhesion molecules and promotion of the transendothelial
      migration of neutrophils in vitro. To investigate the role of spirochetal
      lipoproteins in this process, we assessed the ability of a synthetic
      lipohexapeptide corresponding to the N terminus of B. burgdorferi outer surface
      protein A (OspA) to activate human umbilical vein endothelial cells (HUVEC).
      Using a whole-cell enzyme-linked immunosorbent assay, we demonstrated that OspA
      lipopeptide activated endothelium in a dose-dependent fashion, as measured by
      upregulation of E-selectin. Near-maximal stimulation was achieved with 100
      micromolar lipopeptide. In addition, the lipopeptide increased expression of
      vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1
      (ICAM-1). Similar results were obtained with 25 nM native OspA or lipidated
      recombinant OspA or OspB. Incubation of HUVEC with nonlipidated OspA peptide,
      nonlipidated recombinant OspA or OspB, or tripalmitoyl-S-glyceryl-cysteine had
      little or no effect on expression of these adhesion molecules. A mutant strain of
      B. burgdorferi that lacked OspA and OspB upregulated expression of E-selectin to
      the same degree as its wild-type counterpart, indicating that other spirochetal
      components also possess the ability to activate endothelium. Conditioned medium
      from HUVEC incubated with OspA lipopeptide or lipidated recombinant OspA induced
      chemotaxis of neutrophils in Boyden chamber assays, whereas the OspA preparations
      alone were devoid of chemotactic activity. When HUVEC grown on connective tissue
      substrates were treated with OspA lipopeptide, subsequently added neutrophils
      migrated across the endothelial monolayers. These results implicate the outer
      surface lipoproteins of B. burgdorferi as potential effector molecules in the
      promotion of a host inflammatory response.

PMID- 8757852
TI  - Induction of cytokine gene expression by listeriolysin O and roles of macrophages
      and NK cells.
AB  - To determine the role of listeriolysin O (LLO) of Listeria monocytogenes in the
      host response at the initial stage of infection, cytokine gene expression in
      mouse peritoneal exudate macrophages and spleen cells was examined by reverse
      transcription-PCR. Expression of various cytokine mRNAs, especially those of
      interleukin-1 (IL-1), tumor necrosis factor alpha, gamma interferon (IFN-gamma),
      and IL-12, was observed to occur in spleen cells after direct stimulation with an
      LLO preparation purified to a single band on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Induction of mRNA expression by LLO was not
      blocked by cholesterol, which abrogated the hemolytic activity of LLO. After the
      depletion of NK cells in spleen cells by treatment with anti-asialo GM1 antibody
      plus complement, LLO-induced expression of IFN-gamma was decreased, indicating
      that NK cells were the main source of IFN-gamma. After depletion of macrophages
      by passing spleen cells over a Sephadex G-10 column, expression of macrophage
      derived cytokines, including IL-1alpha, tumor necrosis factor alpha, and IL-12,
      was diminished. In addition, IFN-gamma mRNA expression was impaired, indicating
      that IFN-gamma mRNA expression from NK cells required signaling from macrophages.
      It is suggested that LLO is capable of inducing endogenous cytokines of mice, and
      both NK cells and macrophages are involved in the host cytokine response to LLO.

PMID- 8757853
TI  - Polysaccharide side chains are not required for attaching and effacing adhesion
      of Escherichia coli O157:H7.
AB  - Escherichia coli of the serotype O157:H7 is an enterohemorrhagic human pathogen
      which demonstrates attaching and effacing adhesion to colonocytes in vivo and to
      epithelial cells grown in tissue culture. Transposon TnphoA mutants of E. coli
      O157:H7 strain CL-8 were produced. Two of 300 alkaline phosphatase positive
      mutants, designated JB6 and JB27, did not express O157 side chains as assessed by
      agglutination with specific polyclonal O157 antiserum, silver staining of
      lipopolysaccharide extracts separated by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis, and Western immunoblots with polyclonal O157-specific
      antiserum. Both O157-negative mutants and the parent strain demonstrated
      localized adherence to HEp-2 cells when examined by Giemsa staining and bright
      field microscopy. Furthermore, both O157-negative mutants showed enhanced
      adherence to HEp-2 cells compared with the parent strain when assessed by
      quantification of adherent bacterial CFUs. The parent strain, CL-8, and both of
      the mutants produced fluorescent foci when adherent bacteria and HEp-2 cells were
      stained with fluorescein isothiocyanate-labelled phalloidin. Transmission
      electron microscopy confirmed attaching and effacing adherence of strain CL-8 and
      the OO7-negative mutants to HEp-2 cells. These findings indicate that mutants
      deficient in O157 polysaccharide repeats exhibit adherence to tissue culture
      cells in vitro and that O157 polysaccharide repeats are not required to produce
      the attaching and effacing lesion.

PMID- 8757854
TI  - Naturally acquired Pneumocystis carinii pneumonia in gene disruption mutant mice:
      roles of distinct T-cell populations in infection.
AB  - When kept under strict specific-pathogen-free conditions, H-21-Abeta (Abeta(-/
      ),T-cell receptor beta (TCRbeta(-/-)), and recombinase-activating gene 1 (RAG-1(
      /-) gene disruption mutant mice, deficient in conventional CD4+ T cells,
      TCRalphabeta cells, and all peripheral T and B lymphocytes, respectively,
      consistently developed lethal Pneumocystis carinii pneumonia through natural
      infection. The most severe symptoms appeared in RAG-1(-/-) mutants. In contrast,
      TCRdelta(-/-) and beta2-microglobulin(-/-)(beta2m-/-) mutants, deficient in
      TCRgammadelta cells and conventional CD8alphabeta+ TCRalphabeta cells,
      respectively, were fully resistant to infection. Our data indicate not only the
      insufficiency but also the dispensability of CD8 alphabeta+TCRalphabeta cells and
      of TCRgammadelta lymphocytes in resistance to P. carinii infection. Under disease
      conditions, large numbers of unusual single-positive CD4+ and CD8alphabeta+ as
      well as double-negative TCRgammadelta subpopulations of cells accumulated in
      lungs of TCRbeta(-/-) mutants. This accumulation was consistently accompanied by
      a drastic increase in the pulmonary B-cell population. In contrast, CD8alphabeta+
      TCR alpha beta cells, but no B cells, appeared in lungs of parasitized Abeta (-/
      ) mutants. Since lung damage and parasite numbers were less prominent in morbid
      TCRbeta(-/-) and Abeta(-/-) mutants than in diseased RAG-1(-/-) mice, the
      remaining lymphocytes accumulating in lungs of the former two mutants seem to
      perform residual resistance functions.

PMID- 8757855
TI  - The (alpha2-->8)-linked polysialic acid capsule of group B Neisseria meningitidis
      modifies multiple steps during interaction with human macrophages.
AB  - Group B Neisseria meningitidis causes systemic disease, including meningitis,
      after initial colonization and subsequent penetration of nasopharyngeal mucosa, a
      tissue which is richly populated by macrophages. In an initial effort to
      characterize the interaction of N. meningitidis and mature human macrophages, the
      influence of the alpha2-->8) -linked polysialic acid capsule on the interaction
      of N. meningitidis with human monocyte-derived macrophages was investigated with
      a capsulate case isolate and an isogenic Tn916-derived noncapsulate transformant.
      The capsulate strain was fourfold less adherent to the macrophage surface after
      cold incubation, although adherence of both strains was significantly increased
      after opsonization with nonimmune C5-depleted serum. When opsonized inocula were
      adjusted so that they adhered to macrophages in equal numbers, the two strains
      were internalized at equivalent rates and both entered membrane-bound
      compartments (phagosomes). Colocalization of bacteria with the late endosomal and
      lysosomal marker lysosome-associated membrane protein revealed that fusion of
      lysosomes with phagosomes containing the capsulate organism was significantly
      reduced 10 and 30 min after entry, but by 1 h, no difference between the strains
      was observed. Once internalized, meningococci were effectively killed, although
      more rapid killing of the capsulate strain was observed over the first 3 h. These
      results indicate that the (alpha2-->8)-linked polysialic acid capsule modifies
      the interaction of meningococci with human macrophages at multiple steps,
      including adherence to the macrophage surface and phagosome-lysosome fusion.
      Moreover, the discordance between the kinetics of phagosome- lysosome fusion and
      bacterial killing suggests that a nonlysosomal mechanism may be responsible for a
      significant fraction of macrophage killing of N. meningitidis.

PMID- 8757856
TI  - Pathogenicity island evaluation in Escherichia coli K1 by crossing with
      laboratory strain K-12.
AB  - In bacterial pathogens, strain-specific chromosomal segments often contain genes
      encoding strain-specific traits, and because these genes often appear to be
      dedicated to pathogenic interactions with eucaryotic hosts, the segments
      containing them may be considered so-called pathogenicity islands (G. Blum, M.
      Ott, A. Lischewski, A. Ritter, H. Imrich, H. Tschape, and J. Hacker, Infect.
      Immun. 62:606-614, 1994). We evaluated the contribution to pathogenesis of a
      recently identified strain-specific chromosomal segment from an Escherichia coli
      K1 mammalian-newborn sepsis strain: transfer of E. coli K-12 DNA sequences near
      64 min, by P1 transduction, into K1 strain RS218 resulted in an RS218-K-12
      chimera that (i) contained a shortened NotIotl restriction fragment (relative to
      wild-type RS218) encompassing the 64-min region; (ii) lacked invasiveness in
      newborn rats; and (iii) grew in vitro, in both rich and minimal laboratory media,
      indistinguishably from strain RS218. In addition, genomic DNA from the chimera
      failed to hybridize with sequences of the K1 capsule genes from strain RS218,
      suggesting that the chromosomal segment near 64 min which was lost contained
      these sequences and indeed contained K1-specific virulence genes. Transfer of K
      12 sequences resulting in deletion of E. coli pathogen-specific chromosomal
      segments may afford a general method of detecting genes encoding virulence and/or
      other distinguishing traits.

PMID- 8757857
TI  - Involvement of reactive oxygen intermediates in tumor necrosis factor alpha
      dependent bacteriostasis of Mycobacterium avium.
AB  - We studied the involvement of reactive oxygen intermediates and reactive nitrogen
      intermediates in the bacteriostasis of two Mycobacterium avium strains differing
      in virulence by resident peritoneal macrophages. We found that both the highly
      virulent strain (25291) and the low-virulence strain (1983) of M. avium induced
      superoxide production but inhibited nitrite production in vitro. This inhibition
      was due to the production of superoxide, a nitric oxide scavenger. The
      stimulation of superoxide production was two- to fivefold higher in strain 1983
      infected than in strain 25291-infected resident peritoneal macrophages and was
      independent of contaminating T cells or NK cells. Superoxide secretion was
      dependent on the tumor necrosis factor (TNF) produced endogenously by the
      macrophages. This was also true when macrophages were isolated from infected
      mice. Addition of TNF to the infected resident peritoneal macrophages caused only
      a slight, albeit significant, increase in superoxide production by strain 25291
      infected macrophages. Incubation of resident peritoneal macrophages with
      different scavengers of reactive oxygen intermediates showed that strain 1983 was
      susceptible to hydrogen peroxide produced by resident peritoneal macrophages.
      Strain 25291 was shown to decrease superoxide secretion inside heavily infected
      bone marrow-derived macrophages. This strain was also shown to be a better
      trigger for production of reactive oxygen intermediates than strain 1983. In
      summary, strain 1983 induced high levels of TNF synthesis that acted in an
      autocrine fashion to stimulate production of reactive oxygen intermediates by
      macrophages leading to growth restriction mediated by hydrogen peroxide. The
      highly virulent strain 25291 induced low levels of TNF synthesis, and therefore
      little reactive oxygen intermediate production, and could also inhibit superoxide
      production by the infected macrophages.

PMID- 8757858
TI  - Interleukin-6 is required for a protective immune response to systemic
      Escherichia coli infection.
AB  - Interleukin-6 (IL-6) is a multipotential cytokine detected in the serum of
      patients or experimental animals undergoing bacterial sepsis. To date, the role
      of IL-6 in gram-negative sepsis models has been controversial. We have used IL-6
      deficient mice to investigate the role of IL-6 during virulent Escherichia coli
      infection and in lipopolysaccharide (LPS)-induced mortality. In this report we
      describe an increased susceptibility of IL-6-deficient mice to E. coli infection
      in terms of mortality and accumulation of viable bacteria in tissues, indicating
      a protective role for IL-6 during the immune response against E. coli. In
      contrast, mortality rates of IL-6-deficient mice and control animals undergoing
      LPS-induced shock did not differ, indicating that IL-6 was inconsequential for
      survival in this model. Furthermore, we have shown that neutrophils were crucial
      for resistance to E. coli in normal mice. IL-6-deficient mice were unable to
      efficiently induce neutrophilia in the bloodstream immediately following
      challenge with E. coli, in contrast to a characteristic neutrophilia induced in
      control animals. Prophylactic treatment of the mutant animals with recombinant IL
      6 protein reverted both the deficit of neutrophilia and the accumulation of
      bacteria in tissues. These data clarify the role of IL-6 as protective in
      virulent E. coli infection and suggest that the protective effect may be at least
      partially mediated through neutrophils.

PMID- 8757859
TI  - Roles for tumor necrosis factor alpha and nitric oxide in resistance of rat
      alveolar macrophages to Legionella pneumophila.
AB  - Legionella pneumophila is an intracellular parasite of alveolar macrophages, and
      recovery from legionellosis is associated with activation of alveolar macrophages
      to resist intracellular bacterial replication. Gamma interferon (IFN-gamma) is
      known to activate alveolar macrophages to suppress L. pneumophila, but the role
      of macrophage-derived cytokines in modulating alveolar macrophage resistance is
      unknown. To test the hypothesis that macrophage-derived mediators contribute to
      the resistance of alveolar macrophages to L. pneumophila, we incubated adherent
      rat alveolar macrophages with Escherichia coli lipopolysaccharide (LPS),
      recombinant tumor necrosis factor alpha (TNF-alpha), recombinant IFN-gamma,
      neutralizing anti-TNF-alpha, and/or N(G)-monomethyl-L-arginine (L-NMMA) for 6 h
      before challenge with L. pneumophila. Monolayers were sonically disrupted and
      quantitatively cultured on successive days. We also measured bioactive TNF-alpha
      release by infected macrophages in the presence or absence of IFN-gamma. We found
      that pretreatment of alveolar macrophages with LPS or, to a lesser degree, TNF
      alpha, significantly inhibited intracellular replication of L. pneumophila. Both
      LPS and TNF-alpha acted synergistically with IFN-gamma at less than the maximally
      activating concentration to suppress L. pneumophila growth. The independent and
      coactivating effects of LPS were blocked by anti-TNF-alpha. Killing of L.
      pneumophila by IFN-gamma at the maximally activating concentration was inhibited
      by anti-TNF-alpha. The synergistic effects of TNF-alpha. or LPS in combination
      with IFN-gamma were inhibited by L-NMMA. Infected alveolar macrophages secreted
      TNF-alpha in proportion to the bacterial inoculum, and secretion of TNF-alpha was
      potentiated by cocultivation with IFN-gamma. These data indicate that secretion
      of TNF-alpha is an important autocrine defense mechanism of alveolar macrophages,
      serving to potentiate the activating effects of IFN-gamma through costimulation
      of nitric oxide synthesis.

PMID- 8757861
TI  - Role of Pseudomonas aeruginosa lipase in inflammatory mediator release from human
      inflammatory effector cells (platelets, granulocytes, and monocytes.
AB  - Previously, we have shown that Pseudomonas aeruginosa lipase and phospholipase C
      (PLC), two extracellular lipolytic enzymes, interact with each other during 12
      hydroxyeicosatetraenoic acid (HETE) generation from human platelets. In this
      regard. the addition of purified P. aeruginosa lipase to PLC-containing crude P.
      aeruginosa culture supernatants enhances the generation of the chemotactically
      active 12-HETE from human platelets. Therefore, we analyzed the interaction of
      purified P. aeruginosa lipase and purified hemolytic P. aeruginosa PLC with
      regard to inflammatory mediator release from human platelets, neutrophilic and
      basophilic granulocytes, and monocytes. Purified P. aeruginosa PLC, but not
      purified lipase by itself, induced 12-HETE generation from human platelets, the
      generation of leukotriene B4 (LTB4) and oxygen metabolites, enzyme release from
      human neutrophils, and histamine release from basophils but diminished
      interleukin-8 (IL-8) release from human monocytes in a dose-dependent manner. The
      addition of purified lipase enhanced PLC-induced 12-HETE and LTB4 generation, did
      not influence enzyme, histamine, or IL-8 release, but diminished the PLC-induced
      chemiluminescent response. Similar results were obtained when the hemolytic PLC
      from Clostridium perfringens was used instead of P. aeruginosa PLC. For further
      comparison, we used the well-defined calcium ionophore A23187 and phorbol-12
      myristate-13-acetate (PMA) as stimuli. Lipase enhanced calcium ionophore-induced
      LTB4 generation and beta-glucuronidase release but reduced calcium ionophore
      induced and PMA-induced chemiluminescence. In parallel, we analyzed the role of
      lipase in a crude P. aeruginosa culture supernatant containing PLC and lipase.
      Lipase activity in the P. aeruginosa culture supernatant was inhibited by
      treatment with the lipase-specific inhibitor hexadecylsulfonyl fluoride, leaving
      the activity of PLC unaffected. The capacity of "lipase-inactivated culture
      supernatant" to induce 12-HETE and LTB4 generation was diminished by 50 to 100%.
      Our results suggest that the simultaneous secretion of lipase and PLC by P.
      aeruginosa residing in an infected host may result in severe pathological effects
      which cannot be explained by the sole action of the individual virulence factor
      on inflammatory effector cells.

PMID- 8757860
TI  - Characterization of echinocandin-resistant mutants of Candida albicans: genetic,
      biochemical, and virulence studies.
AB  - The pneumocandins are potent antifungal agents of the echinocandin class which
      are under development for use as broad-spectrum antimycotic therapy. One
      important consideration for any new therapeutic class for treating serious fungal
      infections is the potential for drug resistance development. In this study we
      have isolated and characterized four independent spontaneous Candida albicans
      mutants resistant to the potent semisynthetic pneumocandin L-733,560. These
      mutants have many of the properties of FKS1/ETG1 echinocandin-resistant mutants
      of Saccharomyces cerevisiae, including (i) cross-resistance to other 1,3-beta-D
      glucan synthase inhibitors, such as papulacandin and echinocandins, but no change
      in sensitivity to other antifungal agents; (ii) in vitro glucan synthase activity
      that is more resistant to pneumocandins than the wild-type parent enzyme; and
      (iii) semidominant drug resistance in spheroplast fusion strains. The mutants
      were compared with C. albicans echinocandin-resistant mutants isolated by
      mutagenesis by L. Beckford and D. Kerridge (mutant M-2) (abstr. PS3.11, in
      Proceedings of the XI Congress of the International Society for Human and Animal
      Mycology, Montreal, Canada, 1992) and by A. Cassone, R. E. Mason, and D. Kerridge
      (mutant CA-2) (Sabouraudia 19:97-110, 1981). All of the strains had resistant
      enzyme activity in vitro. M-2 grew poorly and had low levels of enzyme activity.
      In contrast, CA-2 and the spontaneous mutants grew as well as the parents and had
      normal levels of glucan synthase activity. These results suggest that these
      resistant mutants may have alterations in glucan synthase. CA-2 was unable to
      form germ tubes, an ability retained by the spontaneous mutants. The virulence of
      the spontaneous mutants was unimpaired in a mouse model of disseminated
      candidiasis, while M-2 and CA-2 were 2 orders of magnitude less virulent than
      their parent strains. Significantly, mice challenged with the spontaneous mutant
      CAI4R1 responded therapeutically to lower levels of L-733,560 than would he
      predicted by the increase in in vitro susceptibility.

PMID- 8757862
TI  - Biochemical and molecular analysis of phospholipase C and phospholipase D
      activity in mycobacteria.
AB  - Resurgence of mycobacterial infections in the United States has led to an intense
      effort to identify potential virulence determinants in the genus Mycobacterium,
      particularly ones that would be associated with the more virulent species (e.g.,
      Mycobacterium tuberculosis). Thin-layer chromatography (TLC) using radiolabeled
      phosphatidylcholine and sphingomyelin as substrates indicated that cell extracts
      of M. tuberculosis contain both phospholipase C (PLC) and phospholipase D (PLD)
      activities. In contrast, only PLD activity was detected in cell extracts of M.
      smegmatis. Neither activity was detected in cell-free culture supernatants from
      these organisms. We and others recently identified two open reading frames in M.
      tuberculosis with the potential to encode proteins which are highly homologous to
      the nonhemolytic (PlcN) and hemolytic (PlcH) phospholipase C enzymes of
      Pseudomonas aeruginosa. In contrast to the plc genes in P. aeruginosa, which are
      considerably distal to each other (min 34 and 64 on the chromosome), the
      mycobacterial genes, designated mpcA and mpcB, are tandemly arranged in the same
      relative orientation and separated by only 191 bp. Both the mpcA and the mpcB
      genes were individually cloned in M. smegmatis, and PLC activity was expressed
      from each gene in this organism. Hybridization experiments using the mpcA and the
      mpcB genes as probes under conditions of moderate stringency identified sequences
      homologous to these genes in M. bovis, M. bovis BCG, and M. marinum but not in
      several other Mycobacterium species, including M. smegmatis, M. avium, and M.
      intracellulare. TLC analysis using radiolabeled substrates indicated that M.
      bovis and M. marinum cell extracts contain PLC and PLD activities, but only PLD
      activity was detected in M. bovis BCG cell extracts. Sphingomyelinase activity
      was also detected in whole-cell extracts of M. tuberculosis, M. marinum, M.
      bovis, and M. bovis BCG, but this activity was not detected in extracts of M.
      smegmatis. Sphingomyelinase activity was detected in cell extracts from M.
      smegmatis harboring either recombinant mpcA or mpcB. These data indicate that PLC
      and sphingomyelinase activities are associated with the most virulent
      mycobacterial species, while PLD activity was detected in both virulent and
      saprophytic strains.

PMID- 8757863
TI  - Proteins of 30 and 36 kilodaltons, membrane constituents of the Staphylococcus
      aureus L form, induce production of tumor necrosis factor alpha and activate the
      human immunodeficiency virus type 1 long terminal repeat.
AB  - We have previously demonstrated that the membrane of the Staphylococcus aureus L
      form induced tumor necrosis factor alpha (TNF-alpha) from murine macrophages. In
      this study, we purified two proteins which induce TNF-alpha production from a
      human monocytic cell line, THP-1, and murine macrophages. These molecules were
      purified from delipidated membranes by deoxycholic acid extraction, two-step
      anion-exchange chromatography, and preparative electrophoresis. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis of the purified proteins showed for
      each a single band with a molecular mass of 30, and 36 kDa. These proteins were
      heat stable. Polymyxin B did not affect the production of TNF-alpha induced by
      these proteins. Furthermore, these proteins induced comparable levels of TNF
      alpha in both lipopolysaccharide-responsive and -nonresponsive mouse macrophages.
      Pretreatment of murine macrophages with gamma interferon enhanced 30- and 36-kDa
      protein-mediated TNF-alpha production. The 30-kDa protein showed lethal toxicity
      to D-galactosamine-treated mice. The 30- and 36-kDa proteins stimulated the human
      immunodeficiency virus type 1 long terminal repeat in a monocytic cell line but
      not a T-cell line. This effect appeared to be mediated through the induction of
      nuclear factor kappaB. These results indicate that the 30- and 36-kDa proteins,
      membrane constituents of the S. aureus L form, may play a role in S. aureus
      infection and/or in human immunodeficiency virus type 1-infected individuals.

PMID- 8757864
TI  - Evidence for a predominant proinflammatory conjunctival cytokine response in
      individuals with trachoma.
AB  - Immune responses to Chlamydia trachomatis infection in trachoma do not protect
      against reinfection or the development of scarring and blindness. In addition,
      the immunoregulatory contribution of cytokines to the development of conjunctival
      histopathology or protection is undefined. In this study, conjunctival cytokine
      mRNA transcripts were compared among subgroups of chlamydia infection status and
      ocular disease presentations of 50 individuals from an area where trachoma is
      endemic. There was a significant association of elevated interleukin (IL)-1beta,
      transforming growth factor beta1, and tumor necrosis factor alpha transcripts
      with infection, follicular inflammation, and scarring. Both gamma interferon (IFN
      gamma) and IL-2 transcripts were significantly associated with infection;
      slightly elevated IL-2 levels were found in inflammatory disease. High IFN-gamma
      transcript levels were present with follicles and inflammatory disease and to a
      lesser extent with inflammatory scarring. The role of IFN-gamma in protection
      from infection or disease was not apparent from this study, since transcripts
      were frequently present in both chlamydial infection and disease. IL-12 (p40)
      transcripts were elevated in adults and children in association with follicular
      inflammation but not with scarring. IL-4, IL-5, and IL-10 transcripts were not
      detected in any samples. In conclusion, C. trachomatis infection stimulates local
      cytokines which favor a strong cell-mediated and proinflammatory response in both
      the early and later manifestations of trachoma. In addition, cytokine transcript
      levels that were associated with disease but no infection were characteristically
      lower overall than when chlamydia was present.

PMID- 8757865
TI  - Increased susceptibility to primary infection with Listeria monocytogenes in
      germfree mice may be due to lack of accumulation of L-selectin+ CD44+ T cells in
      sites of inflammation.
AB  - The host defense of germfree (GF) mice against primary infection with Listeria
      monocytogenes was compared with that of specific-pathogen-free (SPF) mice. In SPF
      mice, the numbers of bacteria in the peritoneal cavity, liver, and spleen
      decreased gradually to undetectable levels by day 8 after intraperitoneal
      infection with a sublethal dose (2 X 10(3) CFU) of L. monocytogenes. On the other
      hand, the elimination of bacteria in these organs of GF mice was significantly
      impaired at this stage after inoculation. We have reported previously that T
      cells coexpressing L-selectin and CD44 play an important role in protection
      against L. monocytogenes through trafficking to sites of inflammation. Consistent
      with our previous findings, the number of unique L-selectin+ CD44+ T cells in the
      peritoneal cavity was remarkably increased on day 8 after infection in SPF mice,
      whereas such an increase was not evident in GF mice at this stage. Listeria
      specific T-cell proliferation was normally detected in the lymph node cells of GF
      mice inoculated with L. monocytogenes, whereas the T-cell-proliferative response
      of the peritoneal exudate cells of GF mice was significantly impaired compared
      with that of SPF mice. These results suggest that the priming of T cells against
      listerial antigens normally occurs in the peripheral lymphoid organs of GF mice
      but the trafficking of the activated T cells to the inflamed sites may be
      severely impaired in GF mice, resulting in increased susceptibility to infection
      with L. monocytogenes.

PMID- 8757866
TI  - Minimal requirements for murine resistance to infection with Francisella
      tularensis LVS.
AB  - Intraperitoneal or intravenous infection of mice with Francisella tularensis LVS
      is lethal, with an intraperitoneal 50% lethal dose (LD50) approaching a single
      bacterium. Intradermal (i.d.) LVS infection has a much higher LD50, about 10(6)
      bacteria in BALB/cByJ mice, and survival of i.d. infection leads to solid
      generation of immunity against lethal challenge. To define the minimal
      requirements for both initial and long-term survival of i.d. infection, we
      characterized the nature of i.d. LVS infection in lymphocyte-deficient
      BALB/cByJ.scid (scid) mice. scid mice infected i.d. with strain LVS survived for
      about 20 days and then died from overwhelming disseminated infection. However,
      scid mice treated with monoclonal antibodies to gamma interferon, tumor necrosis
      factor alpha, or neutrophils-granulocytes all died within 1 week of infection,
      indicating that these were essential for early control of infection. Studies
      using GKO (gamma interferon knockout) mice emphasized that gamma interferon is
      absolutely required for initial survival of i.d. LVS infection. scid mice could
      be reconstituted for long-term survival of i.d. LVS infection and clearance of
      bacteria by intravenous transfer of splenic lymphocytes or purified B220-/T+
      lymphocytes but not nu/nu lymphocytes. T cells are therefore required for long
      term clearance and survival of i.d. LVS infection; efforts to determine whether
      CD4+ T cells, CD8+ T cells, or both are involved are ongoing.

PMID- 8757867
TI  - Translocation of Shiga toxin across polarized intestinal cells in tissue culture.
AB  - Escherichia coli strains producing Shiga toxins (Stx) 1 and 2 colonize the lower
      gastrointestinal tract in humans and are associated with gastrointestinal and
      systemic diseases. Stx are detectable in the feces of infected patients, and it
      is likely that toxin passes from the intestinal tract lumen to underlying
      tissues. The objective of this study was to develop an in vitro model to study
      the passage of Stx across intact, polarized cell monolayers. Translocation of
      biologically active Stx was examined in four cell lines grown on polycarbonate
      filters. Stx1 translocated across intestinal cell monolayers (CaCo2A and T84
      cells) in an energy-requiring and saturable manner, while the monolayers
      maintained a high level of electrical resistance. Stx1 had no effect on
      electrical resistance or inulin movement across these cell lines for at least 24
      h. Induction of specific Stx receptors with sodium butyrate reduced the
      proportion of toxin translocated across CaCo2A monolayers but had no major effect
      on the movement of horseradish peroxidase or [3H]inulin. We have shown that
      biologically active Stx1 is capable of moving across intact polarized intestinal
      epithelial cells without apparent cellular disruption, probably via a
      transcellular pathway. The data also suggest that the presence of Stx receptors
      on the apical surface of intestinal epithelial cells may offer some protection
      against the absorption of luminal Stx1.

PMID- 8757868
TI  - Regulated expression of Clostridium perfringens enterotoxin in naturally cpe
      negative type A, B, and C isolates of C. perfringens.
AB  - Clostridium perfringens enterotoxin (CPE), the virulence factor responsible for
      symptoms associated with C. perfringens type A food poisoning, is produced by
      enterotoxigenic C. perfringens type A isolates when these bacteria sporulate in
      the gastrointestinal tract. Less than 5% of the global C. perfringens population
      apparently carries the cpe gene. To assess the distribution of cpe-regulatory
      factors, we investigated whether the cpe gene of a C. perfringens food poisoning
      isolate can be expressed and properly regulated (i.e., expressed in a sporulation
      associated manner) when transformed into naturally cpe-negative C. perfringens
      isolates. Sporulation-associated CPE expression was observed when low-copy-number
      plasmids carrying either a 5.7-kb DNA insert, containing the cpe open reading
      frame plus >1 kb each of upstream and downstream flanking sequences from C.
      perfringens food poisoning isolate NCTC 8239, or a 1.6-kb insert, containing only
      the cpe open reading frame of NCTC 8239, were electroporated into cpe-negative C.
      perfringens type A, B, and C isolates. Northern (RNA) blot analysis demonstrated
      that the sizes of the cpe message in the transformants and the naturally
      enterotoxigenic C. perfringens NCTC 8239 were similar and that this message was
      detectable only in sporulating cultures of the transformants or NCTC 8239. These
      studies strongly suggest that many, if not all, cpe-negative C. perfringens
      isolates (including type B isolates, which are not known to naturally express
      CPE) produce a factor(s) involved in normal (i.e., sporulation-associated)
      transcriptional regulation of CPE expression by C. perfringens food poisoning
      isolates. These findings are consistent with this CPE-regulatory factor(s) also
      regulating the expression of other genes in C. perfringens.

PMID- 8757869
TI  - Protective immune responses to apical membrane antigen 1 of Plasmodium chabaudi
      involve recognition of strain-specific epitopes.
AB  - Apical membrane antigen 1 (AMA-1), an asexual blood-stage antigen of Plasmodium
      falciparum, is an important candidate for testing as a component of a malaria
      vaccine. This study investigates the nature of diversity in the Plasmodium
      chabaudi adami homolog of AMA-1 and the impact of that diversity on the efficacy
      of the recombinant antigen as a vaccine against challenge with a heterologous
      strain of P. chabaudi. The nucleotide sequence of the AMA-1 gene from strain DS
      differs from the published 556KA sequence at 79 sites. The large number of
      mutations, the nonrandom distribution of both synonymous and nonsynonymous
      mutations, and the nature of both the codon changes and the resulting amino acid
      substitutions suggest that positive selection operates on the AMA-1 gene in
      regions coding for antigenic sites. Protective immune responses induced by AMA-1
      were strain specific. Immunization of mice with the refolded ectodomain of DS AMA
      1 provided partial protection against challenge with virulent DS (homologous)
      parasites but failed to protect against challenge with avirulent 556KA
      (heterologous) parasites. Passive immunization of mice with rabbit antibodies
      raised against the same antigen had little effect on heterologous challenge but
      provided significant protection against the homologous DS parasites.

PMID- 8757870
TI  - Influence of lipoteichoic acid structure on recognition by the macrophage
      scavenger receptor.
AB  - Lipoteichoic acids (LTAs) belong to the immunostimulatory class of molecules of
      gram-positive bacteria (GPB). Previous investigations showed that the macrophage
      scavenger receptor (SR), a glycosylated trimeric transmembrane protein, binds
      directly to many GPB, possibly via LTA. SR binding to other ligands is dependent
      upon the spatial characteristics of the repeating negative charge of the ligand.
      We therefore investigated SR recognition of LTA species with various charge
      densities and distributions by determining the capacity of these LTAs to compete
      with the binding of metabolically labeled SR to beads coated with the known SR
      ligand polyguanylic acid. Staphylococcus aureus LTA, a classical LTA type
      (unbranched 1,3-linked polyglycerophosphate chain covalently bound to a membrane
      diacylglyceroglycolipid), had a 50% inhibitory concentration (IC50) for
      inhibition of SR binding of 0.84 microg/ml. When the S. aureus LTA was rendered
      more negatively charged by removal of ester-linked alanine from the
      polyglycerophosphate backbone, the IC50 dropped to 0.23 microg/ml. Other
      polyglycerophosphate LTAs from Enterococcus faecalis, Enterococcus faecium,
      Enterococcus hirae, Listeria monocytogenes, Listeria welshimeri, and
      Streptococcus sanguis showed IC50S of 0.5 to 2.1 microg/ml, supporting the role
      of negative charge in binding to SR. Accordingly, the zwitterionic LTA of
      Streptococcus pneumoniae and Clostridium innocuum LTA substituted with positively
      charged sugar residues had no binding capacity. Monoglycerophosphate branches,
      but not succinyl ester, affected binding of lipoglycans. The data presented above
      parallel the previous findings for whole organisms and support the role of
      surface-associated LTA as a major ligand of GPB for binding to SR. Whether
      binding of LTA and whole GPB to macrophages initiates uptake and degradation or
      results in signal transduction remains to be determined.

PMID- 8757871
TI  - The Cu,Zn superoxide dismutases of Aspergillus flavus, Aspergillus niger,
      Aspergillus nidulans, and Aspergillus terreus: purification and biochemical
      comparison with the Aspergillus fumigatus Cu,Zn superoxide dismutase.
AB  - Cu,Zn superoxide dismutases (SODs) have been purified to homogeneity from
      Aspergillus flavus and A. niger, which are significant causative agents of
      aspergillosis, and from A. nidulans and A. terreus, which are much rarer
      causative agents of disease, using a combination of isoelectric focusing and gel
      filtration fast protein liquid chromatography. The purified enzymes have been
      compared with the previously described SOD from the most important pathogen in
      the genus, A. fumigatus (M. D. Holdom, R. J. Hay, and A. J. Hamilton, Free
      Radical Res. 22:519-531, 1995). The N-terminal amino acid sequences of the four
      newly purified enzymes were almost identical and demonstrated homology to known
      Cu,Zn SODs from a range of organisms including that from the previously described
      SOD from A. fumigatus. SOD activity was detectable in the culture filtrates of
      all species, and intracellular Cu,Zn SOD activity as a proportion of total
      protein was highest in early-log-phase cultures. The specific activities of the
      purified enzymes were similar, and all four of the newly described enzymes were
      inhibited by potassium cyanide and diethyldithiocarbamate, known Cu,Zn SOD
      inhibitors. Sodium azide and o-phenanthroline demonstrated inhibition at
      concentrations from 5 to 30 mM, and EDTA also exhibited a varying degree of
      inhibition of SOD activity. However, there were differences in the nonreduced
      molecular masses, the reduced molecular masses, and the isoelectric points of the
      four newly described SODs and the A. fumigatus enzyme; these varied from 55 to
      123 kDa, 17.5 to 19.5 kDa, and 5.0 to 5.9, respectively. Of particular note was
      the observation that the A. fumigatus enzyme was thermostable compared with the
      SODs from the other species; in addition, the A.fiumigatus enzyme retained all of
      its activity at 37 degrees C relative to 20 degrees C, whereas the SODs of A.
      nidulans and A. terreus lost significant activity at the higher temperature.
      Aspergillus Cu,Zn SOD plays a hypothetical role in the avoidance of oxidative
      killing mechanisms, and our data suggest that the thermotolerant A. fumigatus
      Cu,Zn SOD would be more effective in such a protective system than, for example,
      the equivalent enzyme from the more rarely pathogenic A. nidulans.

PMID- 8757872
TI  - Evidence for presence in the cell wall of Candida albicans of a protein related
      to the hsp70 family.
AB  - We have previously reported the isolation of several clones from a cDNA
      expression library from Candida albicans, one of which was associated with a
      constitutively expressed 70-kDa protein. The moiety was present in the beta
      mercaptoethanol extracts of cell walls from both blastoconidia and germ tubes.
      The surface expression of this moiety was revealed by an indirect
      immunofluorescence assay using affinity-purified antibody to the fusion protein
      produced by the clone. The 0.68-kb cDNA insert was sequenced. A database search
      revealed extensive homology with the 70-kDa family of stress or heat shock
      proteins (hsps). The 77% homology with another C. albicans HSP70 sequence
      suggested that this fragment represented a second member of the HSP70 family in
      this organism. Homology ranging from 65 to 76% was observed with members of four
      subfamilies (SSA, SSB, SSC, and SSD) of the Saccharomyces cerevisiae HSP70 gene
      family. The nucleic acid sequence and the deduced amino acid sequence of the open
      reading frame showed greatest homology with SSA1 and SSA2 sequences, and the gene
      corresponding to the cDNA clone was designated C. albicans SSA2. The relationship
      with the SSA family was supported by reactivity of the 70-kDa component with
      antibody recognizing the Ssa proteins of S. cerevisiae. The presence of an hsp70
      in the cell wall was confirmed by two additional methods. Cell wall proteins were
      biotinylated with a non-membrane-permeable derivative to distinguish
      extracellular from cytosolic proteins. Biotinylated hsp70 was detected by Western
      blotting (immunoblotting) among the biotinylated components affinity purified by
      chromatography on streptavidin, thereby establishing its presence in the cell
      wall. Immunoelectron microscopy showed that the 70-kDa component was present at
      the cell surface as well as the outer surface of the plasma membrane and extended
      through the cell wall, occasionally appearing to reach the cell surface through
      channels. Northern (RNA) blot analysis showed that the gene was expressed in
      yeast cells growing in yeast extract-peptone medium at both 25 and 37 degrees C
      and in Lee medium at 25 degrees C and during formation of germ tubes in Lee
      medium 37 degrees C. No obvious increase in the expression level was detected
      after the temperature shift. Members of the hsp70 family have been reported to be
      immunoreactive. The fusion protein produced by the cDNA clone was recognized by
      serum from healthy individuals and patients with candidiasis. Since members of
      the hsp70 family of eucaryotic proteins are associated with chaperone and
      translocation functions, in addition to being immunogenic, this protein may play
      a role in the assembly and function of other cell wall proteins.

PMID- 8757874
TI  - Role of nitric oxide in host defense against an extracellular, metazoan parasite,
      Brugia malayi.
AB  - The mechanisms by which mammalian hosts eliminate microparasites such as bacteria
      and viruses are well established. In viral infections, these mechanisms include
      the interferons, neutralizing and opsonizing antibodies, and cytotoxic T
      lymphocytes. In bacterial infections, polymorphonuclear leukocytes and
      macrophages, often facilitated by opsonizing antibodies, ingest the infectious
      agent and mediate host defense. In addition, complement, in the presence of
      specific antibodies directed against surface antigens, can lyse certain bacterial
      pathogens. In contrast, our understanding of the host defenses against metazoan,
      extracellular parasites is less well grounded. We obtained data by two different
      approaches to document the role of nitric oxide (NO) as a mediator of host
      defense against a human nematode parasite. First, treatment of immunocompetent,
      nonpermissive mice with an inhibitor of NO synthase abrogated resistance to
      Brugia malayi, one of the causative agents of human lymphatic filariasis. Second,
      treatment of permissive, immunodeficient mice with a compound that releases NO
      conferred resistance to infection. These data reinforce studies by James and her
      coworkers (I. P. Oswald, T. A. Wynn, A. Sher, and S. L. James, Comp. Biochem.
      Physiol. Pharmacol. Toxicol. Endocrinol. 108:11-18, 1994) on the role of NO in
      defense against trematode parasites and of Kanazawa et al. (T. Kanazawa, H.
      Asahi, H. Hata; K. Machida, N. Kagei, and M. J. Stadecker, Parasite Immunol. 15:
      619-623, 1993) on cestode parasites.

PMID- 8757873
TI  - Babesia bovis rhoptry-associated protein 1 is immunodominant for T helper cells
      of immune cattle and contains T-cell epitopes conserved among geographically
      distant B. bovis strains.
AB  - The ability of rhoptry-associated protein 1 (RAP-1) of Babesia bovis and Babesia
      bigemina to confer partial protective immunity in cattle has stimulated interest
      in characterizing both B-cell and T-cell epitopes of these proteins. It was
      previously shown that B. bovis RAP-1 associates with the merozoite surface as
      well as rhoptries and expresses B-cell epitopes conserved among otherwise
      antigenically different B. bovis strains. An amino-terminal 307-amino-acid domain
      of the molecule that is highly conserved in the B. bigemina RAP-1 homolog did not
      contain cross-reactive B-cell epitopes. The studies reported here demonstrate
      that B. bovis RAP-1 is strongly immunogenic for T helper (Th) cells from B. bovis
      immune cattle and that like B-cell epitopes, Th-cell epitopes are conserved in
      different B. bovis strains but not in B. bigemina RAP-1. Lymphocytes from cattle
      immune to challenge with the Mexico strain of B. bovis proliferated against
      recombinant B. bovis RAP-1 protein derived from the Mexico strain. T-cell lines
      established by stimulating lymphocytes with recombinant RAP-1 protein responded
      against B. bovis, but not B. bigemina, merozoites. T-cell lines established by
      repeated stimulation of lymphocytes with B. bovis membrane antigen proliferated
      strongly against RAP-1, demonstrating the immunodominant nature of this protein.
      RAP-1-specific CD4+ T cell clones recognized Mexico, Texas, Australia, and Israel
      strains of B. bovis but neither B. bigemina merozoites nor recombinant B.
      bigemina RAP- 1. Analysis of cytokine mRNA in RAP-1-specific Th cell clones
      revealed strong expression of gamma interferon but little or no expression of
      interleukin-2 (IL-2), IL-4, or IL-10. Gamma interferon production was confirmed
      by enzyme-linked imunosorbent assay. These results indicate the potential to use
      selected B. bovis RAP-1 peptides as immunogens to prime for strong, anamnestic,
      strain-cross-reactive type 1 immune responses upon exposure to B. bovis.

PMID- 8757875
TI  - Characterization of the murine antibody response to peptides representing the
      variable domains of the major outer membrane protein of Chlamydia pneumoniae.
AB  - In an attempt to gain more knowledge about the immunogenicity of the variable
      domains (VDs) of the major outer membrane protein (MOMP) of Chlamydia pneumoniae,
      peptides representing these areas were used to immunize BALB/c and C57BL/6 mice.
      Antisera to the peptides and to peptides conjugated to keyhole limpet hemocyanin
      (KLH) were characterized by their ability to recognize the immunizing peptide and
      elementary bodies (EBs) of C. pneumoniae by enzyme-linked immunosorbent assay
      (ELISA) and Western blot (immunoblot). In addition, antiserum was analyzed for
      its molecular specificity by a pepscan as well as its in vitro neutralizing
      ability. In general, results obtained with antisera to the peptides paralleled
      the results obtained with the antisera to the KLH-conjugated peptides except that
      the titers or strength of reaction in the assays was less. Antisera to the VDs in
      both strains of mice gave ELISA titers to the homologous VD peptide ranging from
      1,000 to >64,000. The strength of reactivity with the reduced MOMP as judged by
      Western blot, in most cases, paralleled the ELISA titer to the peptide. However,
      only antisera raised in both strains of mice to the VD1 and VD4 peptides reacted
      strongly with the EBs, suggesting surface exposure of these VDs. In addition,
      antisera to VD3 from C57BL/6 mice gave strong reactivity to EBs. By pepscan
      analysis antisera from both strains of mice reacted with several VD1 and VD3
      octameric peptides, with weaker reactivity being seen with the octameric peptides
      in the other two VDs. This was in contrast to antisera raised to EBs of C.
      pneumoniae TW-183, which identified two immunogenic regions, one in VD1 and the
      other mapped to VD4. While antisera raised to EBs strongly neutralized the
      infectivity of C. pneumoniae, none of the peptide antisera was able to
      neutralize. In addition, peptides to the VDs were not able to block the
      neutralizing ability of the antisera to EBs of C. pneumoniae. Therefore, these
      results suggest that the VDs of the MOMP of C. pneumoniae are surface exposed but
      do not elicit neutralizing antibodies when linear peptides representing them are
      used as the immunogen.

PMID- 8757876
TI  - Distinct characteristics of initiation of the classical and alternative
      complement pathways by Candida albicans.
AB  - Candida albicans is a potent activator of the complement system. The objective of
      this study was to characterize factors that influence the kinetics for activation
      of C3 and binding of C3 fragments to C. albicans. Factors that were examined
      included the surface properties of the yeast and contributions of the classical
      and alternative complement pathways. The results showed that incubation of
      hydrophobic, hydrophilic, or germinating yeast cells in normal human serum (NHS)
      containing radiolabeled C3 led to immediate accumulation of C3 on all three cell
      types, although the rate of accumulation of C3 on germinating cells was lower. An
      examination of the sites for early C3 binding showed that classical pathway
      initiation led to immediate, synchronous binding over the entire cell surface. A
      blockade of the classical pathway by absorption of putative classical pathway
      initiators or by chelation of calcium limited activation to the alternative
      pathway. Binding of C3 solely via the alternative pathway was characterized by a
      significant lag in the initial binding kinetics. In the absence of classical
      pathway initiation, the early cellular sites for C3 binding appeared as random,
      asynchronous foci of C3 that appeared to expand with time. The factor(s)
      mediating rapid deposition of C3 that was characteristic of the classical pathway
      initiation was reciprocally cross-absorbed by hydrophilic and hydrophobic C.
      albicans but was not removed by absorption of NHS with Saccharomyces cerevisiae,
      encapsulated Cryptococcus neoformans, or nonencapsulated C. neoformans. Delayed
      binding of C3 produced by absorption of serum was largely reversed by addition to
      the absorbed serum of immunoglobulin G isolated from NHS, indicating a
      significant role for a naturally occurring anti-C. albicans immunoglobulin C. in
      classical pathway initiation.

PMID- 8757877
TI  - Relative significance of mannose-sensitive hemagglutinin and toxin-coregulated
      pili in colonization of infant mice by Vibrio cholerae El Tor.
AB  - A previously described in-frame deletion in mshA--the gene encoding the
      structural subunit of the mannose-sensitive hemagglutinin pilus--has been
      introduced into the chromosome of three El Tor O1 strains of Vibrio cholerae.
      None of the deltamshA mutants showed significant attenuation or loss of
      colonization potential in the infant mouse cholera model. A second mutation,
      created by insertion of a kanamycin resistance cartridge into deltamshA, also
      failed to affect in vivo behavior. In contrast, strains carrying mutations in
      tcpA (encoding the monomer of the toxin-coregulated pilus [TCP]) were markedly
      attenuated and showed dramatically impaired colonization. This result was in line
      with those of previous studies. Protection tests performed with antibodies to TCP
      and to MshA showed that only the former were able to confer immunity against El
      Tor O1 challenge in this model. Studies with mutants constructed from two O139
      strains similarly suggest that TCP but not mannose-sensitive hemagglutinin pili
      are critical for colonization by strains of this serogroup.

PMID- 8757878
TI  - Functional characterization of a sialyltransferase-deficient mutant of Neisseria
      gonorrhoeae.
AB  - Previous studies indicate that sialylation of lipopolysaccharide (LPS) by host
      CMP-N-acetylneuraminic acid (CMP-NANA) catalyzed by bacterial sialyltransferase
      rendered gonococci resistant to killing by phagocytes, to entry into epithelial
      cell lines, to killing by immune serum and complement, and to absorption of
      complement component C3. These results have been confirmed by comparing a
      sialyltransferase-deficient mutant (strain JB1) with its parent (strain F62) in
      appropriate tests. In contrast to F62, JB1 was very susceptible to killing by
      human polymorphonuclear phagocytes in opsonophagocytosis tests and incubation
      with CMP-NANA did not decrease the level of killing. The inherent resistance of
      F62 in these tests was probably due to LPS sialylation by CMP-NANA and lactate
      present in the phagocytes. A JB1 variant expressing the invasion-associated Opa
      protein was as able to enter Chang human conjunctiva epithelial cells as an Opa
      positive variant of F62, suggesting that the sialyltransferase is not required
      for Opa-mediated entry. After incubation with CMP-NANA, the number of F62 variant
      gonococci entering cells but not that of JB1 variant gonococci was drastically
      reduced. Both JB1 and F62 were killed by incubation with rabbit antibody to
      gonococcal major outer membrane protein, protein I, and human complement, but
      only F62 was rendered resistant to the killing by incubation with CMP-NANA.
      Finally, both JB1 and F62 absorbed similar amounts of complement component C3 and
      the binding was decreased by incubation with CMP-NANA only for the wild type,
      F62.

PMID- 8757879
TI  - Microtubule-disrupting agents inhibit nitric oxide production in murine
      peritoneal macrophages stimulated with lipopolysaccharide or paclitaxel (Taxol).
AB  - Paclitaxel (Taxol), a yew-derived antimitotic agent which binds to microtubules,
      can mimic certain effects of lipopolysaccharide (LPS) on macrophages from LPS
      responder mouse strains. The production of nitric oxide (NO) by the peritoneal
      macrophages of LPS responder C3H/HeN mice stimulated with taxol or LPS was
      partially, but not completely, suppressed by microtubule-disrupting agents, such
      as colchicine, podophyllotoxin, vinblastine, and nocodazole, but not by
      lumicolchicine, an inactive derivative of colchicine. Inducible NO synthase
      protein expression induced by taxol and LPS in the macrophages was also
      suppressed by colchicine, but colchicine did not suppress the transcription of
      iNOS mRNA in the macrophages after stimulation with taxol or LPS. These findings
      suggest that microtubules function in the posttranscriptional processes of iNOS
      protein expression rather than in the transcriptional process of iNOS mRNA and
      the synthetic process of NO molecules.

PMID- 8757880
TI  - The Salmonella virulence plasmid enhances Salmonella-induced lysis of macrophages
      and influences inflammatory responses.
AB  - The Salmonella dublin virulence plasmid mediates systemic infection in mice and
      cattle. Here, we analyze the interaction between wild-type and plasmid-cured
      Salmonella strains with phagocytes in vitro and in vivo. The intracellular
      recovery of S. dublin from murine peritoneal and bovine alveolar macrophages
      cultured in the presence of gentamicin in vitro was not related to virulence
      plasmid carriage. However, the virulence plasmid increased the lytic activity of
      S. dublin, Salmonella typhimurium, and Salmonella choleraesuis for resident or
      activated mouse peritoneal macrophages. Lysis was not mediated by spv genes and
      was abolished by cytochalasin D treatment. Peritoneal and splenic macrophages
      were isolated from mice 4 days after intraperitoneal infection with wild-type or
      plasmid-cured S. dublin strains. The wild-type strain was recovered in
      significantly higher numbers than the plasmid-cured strain. However, the
      intracellular killing rates of such cells cultured in vitro for both S. dublin
      strains were not significantly different. Four days after infection, there was a
      lower increase of phagocyte numbers in the peritoneal cavities and spleens of
      mice infected with the wild-type strain compared with the plasmid-cured strain.
      The virulence plasmid influenced the survival of macrophages in vitro following
      infection in vivo as assessed by microscopy. Cells from mice infected with the
      plasmid-cured strain survived better than those from mice infected with the wild
      type strain. This is the first report demonstrating an effect of the virulence
      plasmid on the interaction of Salmonella strains with macrophages. Plasmid
      mediated macrophage dysfunction could influence the recruitment and/or the
      activation of phagocytic cells and consequently the net growth of Salmonella
      strains during infection.

PMID- 8757881
TI  - Sequence of the toxic shock syndrome toxin gene (tstH) borne by strains of
      Staphylococcus aureus isolated from patients with Kawasaki syndrome.
AB  - To explore whether a novel staphylococcal clone or structural variant of toxic
      shock syndrome toxin 1 is associated with Kawasaki syndrome, six toxigenic
      strains of Staphylococcus aureus from Kawasaki syndrome patients were studied.
      The strains were divisible into two groups based on phenotypic and genotypic
      characteristics and are therefore unequivocally not clonal. Portions of the tstH
      genes of each strain were sequenced. Three were sequenced in their entirety,
      while the remainder were sequenced from codon 66 to codon 137 of the mature
      protein only. Two of the former group differed slightly in the sequences of their
      signal peptides relative to the sequence published for the tstH signal peptide.
      Those differences did not affect toxin processing or secretion. The sequenced
      portions of the regions encoding mature toxic shock syndrome toxin 1 were
      identical in all six strains and corresponded exactly to the published sequence
      of tstH. No evidence was found for the existence of a structural variant of tstH
      uniquely associated with Kawasaki syndrome.

PMID- 8757882
TI  - Stimulation of the ceramide pathway partially mimics lipopolysaccharide-induced
      responses in murine peritoneal macrophages.
AB  - Recent studies have suggested that lipolysaccharide (LPS) stimulates cells by
      mimicking the second-messenger function of ceramide, a lipid generated in the
      cell by the action of sphingomyelinase (SMase). To examine this possibility
      further, we compared the abilities of LPS, SMase, and/or ceramide analogs to
      induce cytokine secretion, modulate gene expression, and induce endotoxin
      tolerance in macrophages. SMase and LPS induced secretion of tumor necrosis
      factor alpha (TNF-alpha) to comparable degrees; however, unlike LPS, SMase failed
      to stimulate detectable interferon activity. Cell-permeable analogs of ceramide
      induced the expression of many LPS-inducible genes; however, the expression of
      interferon-inducible protein 10 (IP-10) and interferon consensus sequence-binding
      protein (ICSBP) mRNAs was significantly lower than that induced by LPS. Both
      SMase-induced TNF-alpha secretion and LPS-induced TNF-alpha secretion were
      inhibited by pretreatment with a serine/threonine phosphatase inhibitor,
      calyculin A. Macrophages preexposed in vitro to LPS to induce a well
      characterized state of endotoxin tolerance secreted little or no TNF-alpha upon
      secondary challenge with either LPS or SMase, whereas macrophages preexposed to
      SMase secreted high levels of TNF-alpha upon secondary stimulation with LPS or
      SMase. Collectively, these results suggest that ceramide activates a subset of
      LPS-induced signaling pathways in murine peritoneal exudate macrophages.

PMID- 8757883
TI  - Characterization of PepB, a group B streptococcal oligopeptidase.
AB  - Group B streptococci were recently reported to possess a cell-associated
      collagenase. Although the enzyme hydrolyzed the synthetic collagen-like substrate
      N-(3-[2-furyl]acryloyl)-Leu-Gly-Pro-Ala, we found that neither the highly
      purified enzyme nor crude group B streptococcal cell lysate solubilized a film of
      reconstituted rat tail collagen, an activity regarded as obligatory for a true
      collagenase. We cloned and sequenced the gene for the enzyme (pepB). The deduced
      amino acid sequence showed 66.4% identity to the PepF oligopeptidase from
      Lactococcus lactis, a member of the M3 or thimet family of zinc
      metallopeptidases. The group B streptococcal enzyme also showed oligopeptidase
      activity and degraded a variety of small bioactive peptides, including
      bradykinin, neurotensin, and peptide fragments of substance P and
      adrenocorticotropin.

PMID- 8757884
TI  - Interleukin-8 gene expression in Staphylococcus aureus-infected endothelial
      cells.
AB  - Interleukin-8 (IL-8) plays a crucial role in the migration of neutrophils to
      bacterium-infected sites. This study investigated IL-8 induction in
      Staphylococcus aureus-infected endothelial cells (EC). We observed that S. aureus
      infected EC were induced to express both IL-8 mRNA and protein, which can promote
      transmigration of neutrophils across an EC monolayer.

PMID- 8757885
TI  - Purification and characterization of the staphylococcal slime-associated antigen
      and its occurrence among Staphylococcus epidermis clinical isolates.
AB  - The Staphylococcus epidermidis slime-associated antigen (SAA) was purified and
      characterized. N-Acetyl-glucosamine accounted for 70% of the dry weight of SAA,
      which was immunolocalized on the ruthenium red-positive material produced by
      slime-positive strains. A total of 59% of slime-producing S. epidermidis clinical
      isolates expressed SAA, while the phenotype slime- SAA+ was never recovered.

PMID- 8757886
TI  - Adhesion of K88ab to guinea pig erythrocytes: effect on membrane enzyme
      activities.
AB  - Nontoxigenic Escherichia coli strains bearing K88 fimbriae have been associated
      with diarrhea in piglets. We have used guinea pig erythrocytes as a model of the
      host cell to study the cellular alterations after adherence of purified K88ab
      fimbriae. Although Mg2+-dependent ATPase was inhibited (up to 61%), Na/K ATPase
      was not. Metabolic enzymes were not significantly affected.

PMID- 8757887
TI  - Ingestion of Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia
      coli by human peritoneal mesothelial cells.
AB  - In the present study we examined whether mesothelial cells can ingest and digest
      bacteria. The results showed that all strains were ingested. Ingested
      staphylococci proliferated abundantly, and only a few were digested. Escherichia
      coli, however, was digested during the first 8 h, whereafter the mesothelial
      cells disintegrated and proliferation of bacteria could be observed. The clinical
      implications of these findings are discussed.

PMID- 8757888
TI  - Granulocyte-macrophage colony-stimulating factor: involvement in control of
      Trypanosoma cruzi infection in mice.
AB  - Several cytokines play crucial roles in Trypanosoma cruzi infection in mice, but
      the involvement of endogenous granulocyte-macrophage colony-stimulating factor
      (GM-CSF) is poorly documented. This report shows that T. cruzi infection of mice
      triggered an early and sharp increase in plasma GM-CSF during the ascending phase
      of parasitemia. The plasma GM-CSF concentration remained stable at the peak of
      parasitemia and subsequently increased in those mice that survived to the acute
      phase. GM-CSF level increased again sharply, while parasitemia was rapidly
      decreasing. Finally, GM-CSF was undetectable, soon after the disappearance of
      circulating parasites. Injection of T. cruzi-infected mice with neutralizing anti
      GM-CSF monoclonal antibodies induced the early appearance of parasitemia and
      aggravated cumulative mortality. In contrast, recombinant mouse GM-CSF (rmGM-CSF)
      caused sharp decreases in both parasitemia and cumulative mortality in T. cruzi
      infected mice. Peritoneal macrophages from rmGM-CSF-treated and infected or
      uninfected mice were less infected ex vivo than those from control mice. Taken
      together these data demonstrate the protective action of endogenous GM-CSF in T.
      cruzi infection. Neutralization of endogenous GM-CSF aggravates infection, while
      exogenous rmGM-CSF decreases both parasitemia and host mortality.

PMID- 8757892
TI  - [Schizophrenia research].

PMID- 8757889
TI  - Tumor necrosis factor primes neutrophils to kill Staphylococcus aureus by an
      oxygen-dependent mechanism and Plasmodium falciparum by an oxygen-independent
      mechanism.
AB  - The cytokine tumor necrosis factor (TNF) plays the important role of priming
      neutrophils for increased antimicrobial activity. We now demonstrate that human
      neutrophils which lack the ability to generate oxygen radicals, from patients
      with chronic granulomatous disease, show TNF-induced enhancement of killing of
      intraerythrocytic stages of Plasmodium falciparum but not of Staphylococcus
      aureus.

PMID- 8757893
TI  - [Fractures of the scaphoid].

PMID- 8757890
TI  - Structural similarities among malaria toxins insulin second messengers, and
      bacterial endotoxin.
AB  - Malaria toxin causes hypoglycemia and induction of tumor necrosis factor.
      Extracts of parasitized erythrocytes which were coeluted and copurified with one
      of the two subtypes of mammalian insulin-mimetic inositolphosphoglycans similarly
      induced fibroblast proliferation in the absence of serum. In addition, induction
      of tumor necrosis factor in macrophages by malaria toxin and by
      lipopolysaccharide from Escherichia coli was enhanced by pretreatment of these
      toxins with alpha-galactosidase. Thus, parasitized erythrocytes contain both
      soluble inositolphosphoglycan-like insulin second messengers and endotoxin-like
      lipidic molecules.

PMID- 8757894
TI  - [Cochlear implants in children--clinical research prepared the way].

PMID- 8757895
TI  - [Schizophrenia. Current biological theories on the etiology].
AB  - Recent biological research on the aetiology of schizophrenia is reviewed. High
      risk studies, family studies, twin studies, adoption studies, molecular genetics
      and studies on the pre- and perinatal environmental factors are reviewed and it
      is concluded that the diathesis-stress-model is still the predominant
      aetiological hypothesis, although the biological environmental factors seem to
      play a minor role. It is also concluded that the international diagnostic systems
      although valid for clinical diagnostic purposes are insufficient for the
      aetiological research of schizophrenia. With a view to finding aetiologically
      valid phenotypes, future research areas with the aim of broadening the phenotype
      or finding endophenotypes are discussed.

PMID- 8757896
TI  - [Pathogenesis of schizophrenia. Illustrated by anatomical, physiological and
      neuropsychological aspects of the brain].
AB  - Research into schizophrenia over the latest years has led to many new
      investigations and results, and a new hypothesis has suggested a defect in the
      neurointegrative function of the central nervous system. Changes in the
      cytoarchitecture of the hippocampus and the entorhinal cortex points towards a
      dysfunction of temporo-limbic structures, probably a result of embryogenesis, and
      as a consequence dysfunction of the prefrontal cortex arises. The hypothesis of
      the defect filter function, which has been placed in the thalamus, explains how
      the schizophrenic person cannot protect himself against various bombardments of
      stimuli. This leads to a deficiency in information processing, known as defective
      automatic categorisation. The long-term memory, especially the semantic memory
      with common knowledge about the world, is affected, which can be of importance to
      the schizophrenic delusions. The discoveries suggest a dysfunction of the cortico
      striato-thalamo-cortical circuit.

PMID- 8757897
TI  - [Psychological theories in relation to the development of schizophrenia].
AB  - A description of schizophrenia is given from a psychodynamic perspective. The
      illness is subsequently illuminated by means of different psychological theories,
      as the characteristic symptomatology is explained through five basic branches of
      psychology: The psychology of perception, motivation, cognition, personality
      formation and developmental psychology. Finally, current treatment-strategies are
      discussed.

PMID- 8757898
TI  - [Healing of scaphoid fractures assessed by tomography. A follow-up study of
      treated patients].
AB  - Thirty-five of 40 patients who had sustained an undisplaced fracture of the waist
      of the scaphoid were reviewed clinically and radiographically (including
      tomography) at a median of 70 (13-120) weeks after injury. All fractures had been
      retained in a below elbow scaphoid plaster for a period of median eight (3-12)
      weeks. End of treatment was based on the absence of "tenderness" over the
      scaphoid and on radiographical signs of fracture union median ten (5-24) weeks
      after injury. At review 28 (80%) of the fractures were united based on standard
      radiographs and tomography. Four fractures ((11%) 95% confidence limits: 3-27%)
      were nonunions and three fractures (9%) were probably united. Tomography gave
      additional information about the state of union if the fracture was visible but
      unclassifiable on standard radiographs. Tenderness over the scaphoid was only
      found in the nonunions and probably united fractures. Radiographic and clinical
      evaluation of the fracture six months after injury is recommended.

PMID- 8757899
TI  - [Vibrio vulnificus infections in Denmark during the summer of 1994].
AB  - The clinical manifestations and epidemiological data of 11 patients infected with
      Vibrio vulnificus found in Denmark during the unusually warm summer of 1994 are
      reported. All patients had been exposed to seawater prior to illness, but none
      had consumed seafood. Nine patients, including four with bacteraemia, developed
      skin manifestations of various degrees of severity. One patient died of septic
      shock despite surgery and treatment with relevant antibiotics. Four patients
      contracted the disease while fishing. High seawater temperature increases the
      risk of V. vulnificus infections even in temperate climates such as the Danish.
      Exposure to seawater, including handling of fresh seafood, during warm periods
      carries a risk of infection with V. vulnificus.

PMID- 8757900
TI  - [Education of young radiologists. A questionnaire by physicians in chief].
AB  - A questionnaire concerning the training of future radiologists and factors
      affecting the quality of specialist training was sent to the heads of all
      radiological departments participating in the training program in Denmark. The
      answers showed that the quality of training and of radiological production were
      suffering due to increasing numbers of investigations and administrative demands
      without a corresponding increase in resources.

PMID- 8757901
TI  - [Sexuality and quality of life. Results from the quality of life-study of 4,626
      Danes aged 31-33 years born at Rigshospitalet 1959-1961].
AB  - From a cohort of 7222 31-33-year-olds we obtained answers to a 317-item quality
      of-life questionnaire that included five questions on sexuality from 4626
      respondents, giving a response rate of 64.1%. Among the women, 1.6% said they
      were bisexual and 1.4% homosexual; the corresponding figures for men were 1.3%
      and 1.1% respectively. The quality of life of bisexual persons was somewhat lower
      than the cohort mean (W: 15.6% lower, M: 19.1% lower), and that of homosexual
      persons was a little lower than the cohort mean (W: 8.5% lower, M: 3.7% lower).
      About a quarter of all respondents said they had sexual problems. Most frequent
      among the women were reduced sexual desire (17.0%) and the absence of a suitable
      sex partner (7.6%), and among the men, the absence of a suitable sex partner
      (12.5%) and premature ejaculation (5.5%). The quality of life of persons with
      sexual problems was measured to be from 7.0% to 24.2% lower than the cohort mean
      (as expressed in terms of this mean). The intermediate-sized relationship between
      sexual problems and quality of life suggests that such problems can be symptoms
      of reduced quality of life, rather than medical problems to be tackled as such.
      Implications for quality life-sensitive clinical practice are discussed.

PMID- 8757902
TI  - [Recurrent arthritis in a child. A rare manifestation of Wilson's disease].
AB  - Wilsons disease is a rare autosomal recessive disorder of copper transportation,
      which is fatal if not treated. The disease often starts in adolescence, and most
      common symptoms are due to liver-and/or brain involvement. This paper deals with
      an adolescent with Wilsons disease. His clinical presentation was joint
      complaints for almost two years. The final diagnosis was made by mutation
      analysis. It is stressed that the clinician should consider Wilson's disease in
      cases of unexplained liver- and neurological involvement as well as cases of
      repetitive unexplained joint symptoms in the pubertal period.

PMID- 8757903
TI  - [Active management of labor--the long way is popular again...].

PMID- 8757904
TI  - Digital distribution.

PMID- 8757905
TI  - A benchmark for dental health advice.

PMID- 8757907
TI  - Is general anaesthesia for orthodontic extractions in children necessary?
AB  - Recent surveys of children have shown the use of general anaesthesia for
      extractions by GDPs has declined while its use in hospitals may actually have
      increased. Shaw and Weatherill argue the aim should be to reduce its use.

PMID- 8757908
TI  - Nerve injury.

PMID- 8757910
TI  - The professional debate continues.

PMID- 8757909
TI  - Recruitment to academic posts.

PMID- 8757911
TI  - Oral cancer.

PMID- 8757912
TI  - Emergency arrangements.

PMID- 8757913
TI  - Anecdotal evidence.

PMID- 8757914
TI  - Dental injuries during general anaesthesia.

PMID- 8757915
TI  - Dental health related behaviours in toddlers in low and high caries areas in St
      Helens, north west England.
AB  - The aim of this investigation was to compare the dental health behaviour of
      toddlers in low caries (A) and high caries (B) communities in St Helens. Parents
      of 60 children aged between 17 and 20 months in community A, and 68 in community
      B were interviewed at home. Using 24-hour dietary recall, sugar intake was
      recorded as sugar episodes-a sugar episode being a half-hour period during which
      any amount of non-milk extrinsic sugars (NMES) was consumed. Exposure to fluoride
      was recorded according to the number of times fluoride toothpaste was used and
      whether a fluoride supplement was given in the 24-hour period. The median sugar
      episode score for community A was 6 per 24-hour period (interquartile range 5 to
      8), compared with 10.5 (7 to 13) for community B. Sixty per cent of parents in
      community A compared with 37% in community B reported brushing their child's
      teeth twice daily with fluoride toothpaste. The respective figures for use of
      fluoride supplements were 12% and 6%. It is concluded that patterns of dental
      health behaviour are established early in children's lives, and that marked
      differences exist between communities within the same district. Recommendations
      are made for oral health promotion policy.

PMID- 8757916
TI  - The use of removable orthodontic appliances in the General Dental Service.
AB  - One hundred and fifty removable appliance cases consecutively sampled by the
      Scottish Dental Practice Board were analysed using the PAR index. The cases were
      assessed as being suited or unsuited to the removable appliance approach based on
      the presenting features previously shown to be effectively treated by removable
      appliances. Using chi-squared tests of association, suitable cases were
      characterised as being in the mixed dentition, had one feature treated and one
      appliance used. Suitable cases on average showed 3-4 PAR points more improvement
      as a result of treatment than equivalent unsuitable cases; regression equations
      are given. Because of the wide variability within the sample it proved impossible
      to predict accurately the expected duration of treatment in the General Dental
      Service.

PMID- 8757917
TI  - Panoramic dental radiography: an aid in detecting individuals prone to stroke.
AB  - Stroke (cerebrovascular accident, CVA) is the third leading cause of death and an
      important cause of hospital admission and long-term disability in England and
      Wales. Atherosclerotic lesions at the bifurcation of the common carotid artery
      are the most common cause of stroke. On occasion, these lesions are partially
      calcified and visible on a conventional panoramic dental radiograph. The atheroma
      may appear either as a nodular radiopaque mass or as two radiopaque vertical
      lines within the soft tissues of the neck at the level of the lower margin of the
      third cervical vertebra (C3). These opacities are separate and distinct from the
      hyoid bone and variably appear above or below it. Dentists should scrupulously
      review the panoramic radiographs of all individuals over the age 55 with medical
      histories (hypertension, diabetes mellitus, hypercholesterolaemia, coronary
      artery disease) and behaviours (smoking, alcohol abuse, dietary indiscretion,
      overweight, sedentary life-style) known to be associated with atherosclerosis and
      stroke.

PMID- 8757918
TI  - Canalicular adenoma of the palatal mucosa.
AB  - The clinical and histological features of a canalicular adenoma occurring in the
      palatal mucosa of a 79-year-old male are described. The management of the case
      prompt referral to a specialist centre, histological confirmation of complete
      excision and an uneventful postoperative course-illustrates the correct
      procedures for what may be regarded as a cure of this neoplastic disease.

PMID- 8757919
TI  - Practical marketing for dentistry. 4. Marketing strategy and planning for dental
      organisations.

PMID- 8757920
TI  - Future prospects for the analysis of complex biological systems using micro
      column liquid chromatography-electrospray tandem mass spectrometry.
AB  - An overview is provided of methods for the study of complex biological processes
      by using micro-column liquid chromatography-electrospray ionization tandem mass
      spectrometry. Procedures discussed include electrospray ionization, micro-column
      liquid chromatography, tandem mass spectrometry, tandem mass spectra data
      interpretation for peptides, and database searching with mass spectral data.
      Several problems in immunology are discussed to illustrate this approach.

PMID- 8757921
TI  - Nitrogen factors for sheepmeat. Part 2. Lamb meat. Analytical Methods Committee.
AB  - Nitrogen factors (the percentage nitrogen on a fat-free basis) for lamb meat were
      estimated using a total of 81 lamb carcases from the UK. The samples included
      carcases representative of the EU class ranges for conformation and fatness. The
      sampling period extended over one year in order to include the three age groups
      under which lamb meat is marketed. The results obtained were compared with those
      reported for mutton in Part 1 of this study and a factor of 3.50 for the whole
      side, on a fat-free basis, for the lean with intermuscular fat was recommended as
      an overall figure for mutton and lamb. There were significant differences between
      the factors for some joints and different factors were recommended for use when
      the type of joint used was known.

PMID- 8757922
TI  - Determination of isotope enrichments of magnesium in microwave-digested
      biological samples by thermal ionization mass spectrometry using a direct loading
      technique.
AB  - The isotope ratios of magnesium were determined in isotopically normal and 26 Mg
      enriched samples of human blood, blood plasma, urine and faeces and bovine
      muscle. The measurements were made with a magnetic sector, thermal ionization
      mass spectrometer (TIMS) equipped with a multiple ion collector system for
      simultaneous detection of the ion currents. The samples were decomposed using
      microwave digestion with HNO3 and HCI. Without further chemical treatment, the
      mineralized samples were deposited together with silica gel and boric acid on
      rhenium filaments, which served as thermal ionization source filaments. This
      method, called the direct loading technique (DLT), results in stable ion signals
      of the magnesium isotopes with isotope ratios indistinguishable from those of
      natural Mg standards within experimental error. Fractionation-corrected 26 Mg/24
      Mg ratios of natural Mg standards were determined with a relative external
      precision of 0.02%. The magnesium recoveries for all of the analysed matrices
      were > or = 97%; 26 Mg was added to calibrated sample solutions to produce
      isotopic enrichments within a range typically appearing in samples of human
      tracer studies. Linear regression analysis of measured versus expected per 1000
      (/1000) enrichments yields y = 0.998x + 0.79. The DLT described here is a simpler
      and quicker method than other methods reported hitherto. It has the advantage of
      avoiding magnesium separation and purification steps prior to TIMS analysis for
      all of the analysed biological samples and thus reduces contamination and
      guarantees optimum magnesium recovery. The reported method improves the
      applicability of stable isotopes of magnesium in human tracer studies.

PMID- 8757923
TI  - Second-derivative synchronous fluorescence spectroscopy for the simultaneous
      determination of naproxen and salicylic acid in human serum.
AB  - Second-derivative synchronous fluorescence spectrometry was used to develop a
      simple, rapid and sensitive spectrofluorimetric method for the simultaneous
      determination of naproxen and salicylic acid in human serum. The method is based
      on the intrinsic fluorescence of naproxen and salicylic acid in chloroform-1%
      acetic acid solution. A delta gamma of 130 nm was used for the direct measurement
      of salicylic acid in the binary mixture, whereas naproxen was determined from
      direct measurements at delta gamma = 60 nm and by means of a correction equation
      which incorporates the concentration of salicylic acid. The range of application
      is 0-14 mg l-1 for naproxen and 0-13 mg l-1 for salicylic acid. The detection
      limits for naproxen and salicylic acid are 0.003 and 0.01 mg l-1, respectively.
      Serum samples are extracted into chloroform-1% acetic acid solution prior to
      instrumental measurement. Analytical recoveries range from 97 to 105% (mean 102%)
      for naproxen and from 97 to 112% (mean 103%) for salicylic acid. The within-run
      precision (RSD) for the method for four naproxen-salicylic acid mixtures varied
      from 1.2 to 6.7% and the day-to-day precision for mixtures varied from 2.1 to
      5.0%.

PMID- 8757924
TI  - Observation of albumin resonances in proton nuclear magnetic resonance spectra of
      human blood plasma: N-terminal assignments aided by use of modified recombinant
      albumin.
AB  - Two-dimensional total shift correlation spectroscopy (TOCSY) and double-quantum
      filtered phase-sensitive homonuclear shift-correlated spectroscopy (DQF-COSY) 1H
      NMR spectra are used to assign peaks for about one sixth of the amino acids
      residues of isolated human serum albumin (67 kDa) to amino acid types. Sequential
      assignments are presented for 1H NMR resonances of the N-terminal residues Asp1,
      Ala2 and His3 of human serum albumin (HSA). These are based on pH-dependent
      chemical shifts reflecting the titrating N-terminal NH2 and the His3 imidazole
      ring, in addition to DQF-COSY and TOCSY experiments. Studies of variant
      recombinant human albumin with Asp1 deleted, rHA(2-585), aided the assignments.
      The structural nature of the N-and C-termini of HSA are discussed and pKa values
      of 7.9 and 6.3 were determined for the N-terminal amino group and His3 imidazole
      ring, respectively. About 20 spin systems for albumin, including those for the N
      terminal amino acids, were assigned in 1H NMR spectra of blood plasma buy
      comparison with isolated albumin. Resonances for lipids within lipoproteins and
      also several low molecular mass components can also be assigned in 2D TOCSY 1H
      NMR spectra of plasma.

PMID- 8757925
TI  - Strategy for fractionating high-affinity antibodies to steroid hormones by
      affinity chromatography.
AB  - A general strategy for fractionating high-affinity antibodies to steroid hormones
      has been developed and applied to the fractionation of an antiserum to
      testosterone 3-(O-carboxymethyl)oxime-bovine serum albumin. If the antibodies
      interacting with a stationary phase containing a low concentration of immobilized
      steroid are considered as monovalent binders, a simple equation can be applied to
      show that the affinity of the antibody-stationary phase interaction must be
      higher than about 2 x 10(6) l mol-1 in order to avoid the loss of antibodies
      during the loading and washing of the column. Conversely, to elute the retained
      antibodies, the affinity must be decreased to a value lower than about 2 x 10(5)
      l mol-1 and the dissociation rate constants of the antibody-steroid complexes
      must be >> 1 s-1. In order to prepare an affinity column that satisfies these
      conditions, the ligand to be immobilized was selected on the basis of the cross
      reactions of the antiserum with several testosterone derivatives. Moreover, the
      dissociation rate constants of several antibodies of known affinity were
      measured, together with the effect of acidic buffers and various organic solvents
      on the antiserum-testosterone interaction. Then, an affinity column, prepared by
      coupling testosterone 17 beta-acetate to AH-Sepharose 4B, was used to load the
      antiserum without loss of antibodies during the washing step. The retained
      antibodies were successfully eluted by a mixture of 30% dioxane in phosphate
      citrate buffer (pH 3.4). The affinity of the eluted antibodies was in the range 7
      x 10(9)-2 x 10(11) l mol-1 and was linearly related to the retention volume.
      These results confirm that high-affinity antibodies can be fractionated to
      steroid hormones by a proper choice of the ligand on the stationary phase and the
      eluent composition.

PMID- 8757926
TI  - Flow injection microscopy: a novel tool for the study of cellular response and
      drug discovery.
AB  - Studying responses of live cells to agonists, antagonists and other physical
      stimuli offers insight into their complex membrane and internal biochemistry. An
      experimental technique has been developed in which responses of living cells in
      an inverted radial flow chamber are continuously monitored while being repeatedly
      stimulated using controlled pulses of a biologically active ligand. Precisely
      defined flow conditions result in reproducible peaks which can be numerically
      analysed by comparison with a tracer curve obtained by substituting a dye for the
      stimulus. Exploratory studies have demonstrated that the flow injection technique
      can provide a novel method for kinetics of receptor binding and cellular
      responses. Flow injection microscopy (FIM) allows identification of biologically
      active ligands and their ranking based on measurement of the cellular responses
      in a short time frame. The use of FIM for rapid drug screening, through
      monitoring of the initial kinetics of cellular responses, is demonstrated on a
      model system.

PMID- 8757927
TI  - Enzyme linked immunosorbent assay for detecting benzodiazepines in urine.
AB  - A relatively simple ELISA technique was developed for the detection of a range of
      benzodiazepines (BZs) in urine. The assay employs a mouse anti-oxazepam antibody
      that is highly specific for the BZs. The limit of detection using 10 microliters
      samples of urine was 0.3 microgram ml-1 oxazepam. N-Desmethyldiazepam showed
      equal cross-reactivity to oxazepam, 11 BZs cross-reacted weakly and flurazepam
      and chlordiazepoxide did not cross-react at levels reported to be found in urine.
      No cross-reactivity was observed with drugs of abuse and a range of therapeutic
      drugs commonly found in urine. The assay was used as a screen to detect the
      presence of BZs in urine from 88 addicts that had been screened by the EMIT
      technique and a radioreceptor assay (RRA) for BZs. The ELISA produced two false
      negatives that were EMIT and RRA positive whereas the EMIT produced four
      different false negatives that were positive by both ELISA and RRA. Thirty-three
      positives were common to all three assays. The ELISA was also used to monitor
      nitrazepam-like activity in the urine of a greyhound receiving 5 mg oral
      medication and the results were compared with those obtained by RRA. Both assays
      were able to detect nitrazepam-like activity for up to 10 h post-administration.

PMID- 8757928
TI  - Direct determination of some phenothiazine sedatives in greyhound urine by
      fluoroimmunoassay.
AB  - Antibodies have been raised in rabbits to a chlorpromazine sulfoxide-bovine serum
      albumin immunogen and the resulting antiserum used to develop a magnetizable
      solid-phase antibody fluoroimmunoassay for the detection of sulfoxide metabolites
      of commonly used phenothiazine and thioxanthine neuroleptics. These assays were
      used to screen metabolite levels in the urine of a greyhound following oral
      medication with chlorpromazine in order to assess the potential of these assays
      as simple screens for detecting exposure of racing greyhounds to such sedatives.
      The urine samples were also screened for neuroleptic content using an established
      radioreceptor assay and by TLC. The immunoassay described represents a relatively
      simple, sensitive and group-specific alternative method for screening for
      medication with phenothiazine and structurally similar sedatives in urine
      samples.

PMID- 8757929
TI  - Validation of an automatic urea analyser used in the continuous monitoring of
      hemodialysis parameters.
AB  - The validation of an automatic urea analyser used in the monitoring of
      hemodialysis processes is reported. The analyser can indirectly determine
      dialysis parameters as dialysis delivery (KT/V) and protein catabolism (PCRn).
      These parameters are useful for the prescription and optimization of
      hemodialysis. The analyser, based on a previously-reported flow-injection
      analytical biosystem, was connected on-line to the effluent of a dialysis machine
      during several hemodialysis sessions. The urea concentration data were
      continuously processed and dialysis parameters were obtained in quasi real time
      by means of the integration of an adjusted time-dependent exponential function.
      These values were compared with those obtained by applying the methods
      traditionally employed in hospital laboratories. The evaluation comprised 24 data
      sets from several patients of different gender and age. No significant
      differences were found between the KT/V and PCRn results obtained with the usual
      method and those results produced by the analyser proposed here.

PMID- 8757930
TI  - Use of proficiency tests to assess the comparative performance of analytical
      methods: the determination of fat in foodstuffs.
AB  - The determination of fat in foodstuffs is a common analytical task. Hitherto
      there has been no authoritative comparative exercise to assess the available
      methods by means of results from a large number of laboratories. In this paper
      four different empirical methods of analysis for fat are compared using the
      results generated from a proficiency testing scheme. The results show significant
      bias between some of the different methods, confirming the empirical nature of
      the determination.

PMID- 8757931
TI  - Trace elements in a commercial freeze-dried human urine reference material.
AB  - A large batch of freeze-dried human urine reference material, Seronorm Trace
      Elements Urine, Lot 101021, was prepared commercially (Nycomed Pharma AS, Oslo,
      Norway) for quality control purposes in trace element analysis. Analytes are
      being determined by a voluntary, international co-operative effort so that the
      material will be available to the scientific community at modest cost. The
      material is in stoppered glass vials and is to be reconstituted with 5.00 ml of
      water prior to use. We have evaluated the trace element content for several
      elements, including chromium and zinc, elements for which we have two independent
      methods available for the determinations, namely isotope dilution mass
      spectrometry (IDMS) and atomic absorption spectrometry (AAS). We also report on
      other trace elements measured by IDMS alone, such as Se, for which we have
      enriched stable isotopes available. Results for chromium indicate a mean +/-
      standard deviation (n = 10) of 1.2 +/- 0.3 (by IDMS) and 1.4 +/- 0.3 (by AAS) ng
      Cr per ml of reconstituted urine, indicating possible inhomogeneity and/or
      contamination (21-25% relative standard deviation, RSD). Approximately half of
      the observed chromium originates from the sample container. The values observed
      for zinc were 590 +/- 90 ng ml-1 (15% RSD) for freshly reconstituted material,
      760 +/- 60 ng ml-1 (8% RSD) for material reconstituted 4 d earlier, and 940 +/-
      60 ng ml-1 (6% RSD) 2 months after reconstitution. Selenium values by IDMS were
      very reproducible, with a mean concentration of 16 +/- 0.15 ng g-1 (0.9% RSD),
      suggesting little or no contamination and a high degree of sample homogeneity for
      this element. The source of potential contaminants has been evaluated by
      multielement determinations of leachates of the vials and stoppers. Elements
      noted in significant amounts include B, Ba, Sr, Mo, Cu and Zn, with most of the
      zinc coming from the rubber stopper.

PMID- 8757932
TI  - Plant cell enlargement and the action of expansins.
AB  - Plant cells are caged within a distended polymeric network (the cell wall), which
      enlarges by a process of stress relaxation and slippage (creep) of the
      polysaccharides that make up the load-bearing network of the wall. Protein
      mediators of wall creep have recently been isolated and characterized. These
      proteins, called expansins, appear to disrupt the noncovalent adhesion of matrix
      polysaccharides to cellulose microfibrils, thereby permitting turgor-driven wall
      enlargement. Expansin activity is specifically expressed in the growing tissues
      of dicotyledons and monocotyledons. Sequence analysis of cDNAs indicates that
      expansins are novel proteins, without previously known functional motifs.
      Comparison of expansin cDNAs from cucumber, pea, Arabidopsis and rice shows that
      the proteins are highly conserved in size and amino acid sequence. Phylogenetic
      analysis of expansin sequences suggests that this multigene family diverged
      before the evolution of angiosperms. Speculation is presented about the role of
      this gene family in plant development and evolution.

PMID- 8757933
TI  - Dosage compensation in Drosophila and the "complex' world of transcriptional
      regulation.
AB  - The purpose of this review is to draw attention to the mechanism of dosage
      compensation in Drosophila as a model for the study of the regulation of gene
      activity through the modulation of transcription. Dosage compensation resembles
      some mechanisms of transcriptional regulation, found in widely divergent
      organisms, that do not play a role in the activation of silent genes but
      determine the level of activity of genes that have been induced through the
      action of specific activators. It differs from other known regulatory mechanisms
      in that its effect is to achieve, on average, a twofold change in gene activity
      levels. This review introduces the notion that, in order to yield such a defined
      level of regulation, the mechanism of dosage compensation in Drosophila, and
      perhaps in Caenorhabditis as well, incorporates elements that govern both
      transcriptional enhancement and repression within the same multi-protein
      regulatory complex.

PMID- 8757934
TI  - Modulation by nitric oxide of metalloprotein regulatory activities.
AB  - In many cells, a nitric oxide (NO) synthase inducible by immunological stimuli
      produces a sustained flow of NO that lasts a long time. NO is a short-lived
      molecule but it is a diffusible ligand believed to be capable of reaching distal
      target sites. Further, several lines of evidence indicate that cysteine-rich
      motifs of metal-binding proteins, as well as redox-sensitive metal clusters of
      metalloproteins, are natural sensors of bioradicals like NO. In metalloregulatory
      proteins, metals are often conveniently located at binding sites and bound to
      cysteine residues. Accordingly, disruption of the metal-thiolate polymetallic
      clusters should trigger significant remodelling of the protein structure involved
      in regulation. We can therefore postulate that the nitrosation reaction occurring
      at metal centres or cysteine-rich motifs will preclude correct binding to
      regulatory sites. Several examples are given of metalloregulatory proteins whose
      metal is bound to thiols and may then become sensitive to NO. Recent observations
      indicate that in response to NO synthesis, iron regulatory protein, a eukaryotic
      bifunctional [Fe-S] protein, switches from acting as aconitase to being an RNA
      binding regulator, and we suggest that the interplay between NO or a NO-derived
      molecule and metal clusters at critical allosteric sites may be a crucial
      component of the cellular response to environmental stress.

PMID- 8757935
TI  - Protein kinase cascades activated by stress and inflammatory cytokines.
AB  - Signal transduction pathways constructed around a core module of three
      consecutive protein kinases, the most distal being a member of the extracellular
      signal-regulated kinase (ERK) family, are ubiquitous among eukaryotes. Recent
      work has defined two cascades activated preferentially by the inflammatory
      cytokines TNF-alpha and IL-1-beta, as well as by a wide variety of cellular
      stresses such as UV and ionizing radiation, hyperosmolarity, heat stress,
      oxidative stress, etc. One pathway converges on the ERK subfamily known as the
      "stress activated' protein kinases (SAPKs, also termed Jun N-terminal kinases,
      JNKs), whereas the second pathway recruits the p38 kinases. Upstream inputs are
      diverse, and include small GTPases (primarily Rac and Cdc42; secondarily Ras)
      acting through mammalian homologs of the yeast Ste20 kinase, other kinase
      subfamilies (e.g. GC kinase) and ceramide, a putative second messenger for
      certain TNF-alpha actions. These two cascades signal cell cycle delay, cellular
      repair or apoptosis in most cells, as well as activation of immune and
      reticuloendothelial cells.

PMID- 8757936
TI  - Molecular analysis of Fanconi anaemia.
AB  - The autosomal recessive genetic disease, Fanconi anaemia, is perceived as another
      manifestation of defective cellular DNA repair, just as in the autosomal
      recessive disease Xeroderma pigmentosum. The biochemistry and cellular biology of
      Xeroderma pigmentosum have been convincingly elucidated, but the same has not
      been true for Fanconi anaemia. In this review we consider the pleiotropic nature
      of Fanconi anaemia, its clinical and cellular variability and its genetic
      heterogeneity. We take into account the wealth of experimental findings available
      and offer a novel hypothesis involving feedback control of DNA replication during
      S phase of the cell cycle to explain the basic defect in the disease.

PMID- 8757937
TI  - Genomic imprinting in unstable DNA diseases.
AB  - Evidence for recombination suppression has been identified in linkage studies of
      several unstable DNA diseases. Also sex-specific changes in recombination
      frequency have been detected at the loci of Huntington's disease and myotonic
      dystrophy. It can be hypothesized that meiotic recombination is regulated by
      genome-wide genomic imprinting and that changes in meiotic recombination imply
      the presence of the genomic imprinting defect. If aberrant recombination at the
      locus of trinucleotide repeat expansion is verified, new theoretical and
      experimental opportunities will arise in studies on the role of genomic
      imprinting in the unstable DNA disease.

PMID- 8757938
TI  - Pattern formation: regional specification in the early C. elegans embryo.
AB  - Recent findings suggest that C. elegans, albeit displaying an invariant cell
      lineage for embryonic development, uses the same basic strategy for embryogenesis
      as other organisms. The early embryo is regionalised by cell-cell interactions.

PMID- 8757939
TI  - Trabeculation in the embryonic heart.

PMID- 8757940
TI  - Choice of microbial host for the naphthalene dioxygenase bioconversion.
AB  - The use of whole cell biotransformations for single and multistep enzyme
      conversions is gaining widespread application. In this study the naphthalene
      dioxygenase nah A gene was transferred into Pseudomonas aeruginosa PAC 1R,
      Escherichia coli JM107 and Pseudomonas putida PpG 277. The effect of ethanol on
      these genetically engineered Gram-negative bacteria was studied by measurement of
      enzyme activity, stability and cell integrity. Ethanol has been used in
      biotransformations as a co-substrate carbon source for co-factor recycling and as
      a co-solvent increasing dissolved substrate and product levels. Ethanol increased
      the dissolved substrate (naphthalene) concentration slightly and dissolved
      product ((+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene) by approximately 30%
      at 4% (w/v) ethanol. Both P. aeruginosa PAC 1R and P. putida PpG 277 showed
      decreased activity with increasing ethanol concentration whilst E. coli enzyme
      activity increased with increasing ethanol concentration being comparable to that
      when glucose was used as a carbon source. This project highlighted the many
      factors involved in the selection of microbial hosts for whole cell
      biotransformation processes.

PMID- 8757941
TI  - Fungal colonization of fiberglass insulation in the air distribution system of a
      multi-story office building: VOC production and possible relationship to a sick
      building syndrome.
AB  - Complaints characteristic of those for sick building syndrome prompted
      mycological investigations of a modern multi-story office building on the Gulf
      coast in the Southeastern United States (Houston-Galveston area). The air
      handling units and fiberglass duct liner of the heating, ventilating and air
      conditioning system of the building, without a history of catastrophic or chronic
      water damage, demonstrated extensive colonization with Penicillium spp and
      Cladosporium herbarum. Although dense fungal growth was observed on surfaces
      within the heating-cooling system, most air samples yielded fewer than 200 CFU m
      3. Several volatile compounds found in the building air were released also from
      colonized fiberglass. Removal of colonized insulation from the floor receiving
      the majority of complaints of mouldy air and continuous operation of the units
      supplying this floor resulted in a reduction in the number of complaints.

PMID- 8757942
TI  - Mineralization of 2,4,6-trinitrophenol (picric acid): characterization and
      phylogenetic identification of microbial strains.
AB  - Four bacterial strains that use picric acid as their sole carbon and energy
      source were isolated. Mineralization of 14C-UL-picric acid showed that up to 65%
      of the radioactivity was released as 14CO2. HPLC and UV/Vis spectral analyses
      indicated complete degradation of picric acid by these organisms. HPLC and LC/MS
      analyses showed transient formation of 2,4-dinitrophenol during picric acid
      degradation. Degradation of picric acid was concomitant with stoichiometric
      release of three moles of nitrite per mole of picric acid. The four picric acid
      degraders were identified as close relatives of Nocardioides simplex (ATCC 6946)
      based on their small subunit (16S) rRNA gene sequences.

PMID- 8757943
TI  - Independent pathways for de-repression of the mouse Ig heavy chain germ-line
      epsilon promoter: an IL-4 NAF/NF-IL-4 site as a context-dependent negative
      element.
AB  - The activation of germ-line promoters in the Ig heavy chain loci is regulated by
      cytokines as part of the regulation of B cell commitment to production of new
      antibody isotypes. Activation of the germ-line promoter of the epsilon heavy
      chain locus (Gepsilon) and production of IgE are induced by IL-4 and each is
      virtually undetectable in the absence of IL-4 or the homologous cytokine IL-13.
      Basal expression of the Gepsilon promoter is repressed by the non-histone
      chromosomal protein HMG-I(Y), which also contributes to promoter inducibility,
      and IL-4 stimulates phosphorylation of the C-terminus of HMG-I(Y) through a
      rapamycin-sensitive pathway. IL-4 treatment of mouse B cells also induces a
      Gepsilon DNA binding activity with the properties of IL-4 NAF, which is rapidly
      induced and requires phosphotyrosine for DNA binding activity. This protein binds
      to a different site from HMG-I(Y), but the IL-4 NAF/NF-IL-4 binding site also is
      a negative element more active in repression of basal transcription of the
      Gepsilon promoter. This site acts as a negative element when transferred to the
      thymidine kinase promoter, but does not confer inducibility. In contrast to HMG
      I(Y), IL-4 NAF/NF-IL-4 activation is refractory to rapamycin but sensitive to
      genistein. These findings indicate that two independent signal transduction
      pathways diverge from the IL-4 receptor and suggest that normal expression of
      Gepsilon RNA or IgE is low in part because the germ-line promoter is kept in a
      state of repression which requires de-repression through several cooperative
      pathways. These pathways target conserved nucleotide sequence motifs whose
      precise function depends on the promoter context in which they are situated.

PMID- 8757944
TI  - Bcl-2 protects against Fas-based but not perforin-based T cell-mediated
      cytolysis.
AB  - Fas ligand and perforin are the two key effector mechanisms in T cell-mediated
      cytotoxicity. These molecules mediate cytolysis of target cells by membrane
      damage and apoptosis. bcl-2 is known to protect cells against apoptosis induced
      by many stimuli including growth factor removal. However bcl-2's effect on Fas
      ligand and perforin-induced lysis has not been studied extensively. We
      investigated the effect of overexpression of bcl-2 alone, Fas alone or their
      combined overexpression on lysis of a commonly used target, P815, by perforin
      sufficient, Fas ligand-sufficient and perforin-deficient or Fas ligand-deficient,
      allospecific cytotoxic T lymphocytes (CTL). Wild-type P815 are susceptible to
      lysis by perforin-sufficient CTL, regardless of the presence or absence (gld) of
      Fas ligand, but are poorly lysed by perforin-deficient CTL. Fas transfection of
      P815 makes target cells highly susceptible to lysis by both perforin-sufficient
      and -deficient CTL, indicating the presence of the Fas ligand-mediated
      cytotoxicity on both types of CTL. Co-transfection of P815-fas with bcl-2
      abolishes their increased susceptibility to Fas-mediated lysis, even in the face
      of Fas overexpression on the cell membrane. The protective effect of bcl-2
      against cell lysis is evident with perforin-deficient CTL as effector cells or
      when perforin activity is eliminated by the absence of extracellular calcium in
      perforin-sufficient CTL. bcl-2 overexpression by P815, however, does not protect
      against CTL lysis by the perforin pathway, regardless of Fas overexpression, as
      demonstrated by fas ligand mutated gld and wild-type perforin-sufficient CTL.
      Therefore bcl-2 can protect P815 target cells against Fas-mediated lysis when
      triggered by the Fas ligand on CTL, but not against perforin-mediated lysis.

PMID- 8757945
TI  - The level of tumor necrosis factor-alpha producing cells in the spinal cord
      correlates with the degree of Theiler's murine encephalomyelitis virus-induced
      demyelinating disease.
AB  - The levels of tumor necrosis factor (TNF)-alpha producing cells were analyzed in
      mice with Theiler's murine encephalomyelitis virus-induced demyelinating disease
      (TMEV-IDD). Using an ELISPOT assay, we demonstrate an increase in TNF-alpha
      producing cells in the spinal cords of TMEV-infected SJL/J mice, especially at an
      active disease stage. The numbers of TNF-alpha producing cells were extremely
      high in susceptible SJL/J mice compared with the numbers in resistant BALB/c and
      C57BL/6 mice. TNF-alpha producing cells were also immunohistochemically
      identified in active lesions of TMEV-IDD at acute as well as chronic stages. The
      percentage of TNF-alpha producing cells compared with the total number of cells
      isolated from spinal cords was higher in TMEV-infected SJL/J mice than resistant
      BALB/c and C57BL/6 mice. Correspondingly, the level of TNF-alpha was much higher
      in the culture supernatants of both infiltrating cells in the spinal cords and
      spleen cells from clinically affected animals than that from similarly treated
      resistant mice. Treatment of virus-infected mice with a mAb specific for TNF
      alpha at the beginning of the onset of disease suppressed the development of the
      demyelinating disease. These findings suggest that TNF-alpha may play an
      important role in the pathogenicity of TMEV-IDD.

PMID- 8757946
TI  - Treatment of old mice with IL-2 corrects dysregulated IL-2 and IL-4 production.
AB  - Splenic T cells from old BALB/c mice, activated in vitro with antibody to
      CD3epsilon, secrete more IL-4 but less IL-2 than splenic T cells from young mice.
      The age-associated increase in IL-4 secretion is associated with a significantly
      increased concentration of intracellular IL-4 and its mRNA, although there is no
      increase in the number of activated T cells with intracellular IL-4. In contrast,
      the age-associated decrease in IL-2 secretion is associated with a significant
      decrease in the number of activated T cells with intracellular IL-2. In vivo
      there is a similar age-associated change in the number of activated T cells with
      detectable cytokine. The number of activated T cells with intracellular IL-4 is
      comparable in old and young mice, while the number of activated T cells with
      intracellular IL-2 is significantly decreased in old compared with young mice. Of
      great interest is the fact that old mice continuously exposed to IL-2 in vivo
      following the transplantation of J558 cells expressing the transfected IL-2 gene
      product have an increased number of splenic T cells with intracellular IL-2 that
      equals the level of such cells observed in young mice. Most important, the effect
      of continuous IL-2 administration in vivo was stable as spleen cells from old, IL
      2-treated mice when stimulated in vitro with anti-CD3epsilon had a young-like
      pattern of both intracellular IL-2 and IL-4 expression as well as IL-2 and IL-4
      secretion following in vitro activation. Thus, it appears that exposure of old
      mice to exogenous IL-2 can redress the age-associated imbalance in cytokine
      expression in vivo and cytokine secretion in vitro.

PMID- 8757947
TI  - Activation-induced cell death in murine T cell hybridomas. Differential
      regulation of Fas (CD95) versus Fas ligand expression by cyclosporin A and FK506.
AB  - We have previously reported that activation of murine T cell hybridomas leads to
      expression of Fas (CD95) and its ligand (FasL) which subsequently interact, even
      on the same cell, leading to apoptotic cell death. Since the immunosuppressive
      drugs cyclosporin A (CsA) and FK506 block activation-induced apoptosis in T cell
      hybridomas, we examined whether such compounds affect cell death by interfering
      with expression of Fas, FasL or both, or whether they block Fas signal
      transduction. We have found that CsA- and FK506-treated cells did not exhibit
      transcription of FasL mRNA after activation and were lacking functional FasL
      protein on their surface as determined by staining and the ability to induce
      apoptosis in Fas+ target cells. In contrast, no inhibition of the elevated Fas
      mRNA expression was observed in cells activated in the presence of CsA or FK506.
      Surprisingly, however, cell surface Fas levels were consistently lower on cells
      activated in the presence of immunosuppressive drugs than on activated cells,
      suggesting Fas expression is regulated at several levels. Nevertheless, cells
      activated in the presence of CsA or FK506 underwent apoptosis upon treatment with
      anti-Fas antibody, while unactivated cells did not. Furthermore, CsA and FK506 do
      not interfere with Fas signaling since anti-Fas induced apoptosis in Fas+ target
      cells was unaffected by these drugs. We therefore conclude that CsA and FK506
      block activation-induced apoptosis in T cell hybridomas predominantly by
      interfering with activation signals leading to FasL expression and, further, that
      the regulation of the expression of Fas and FasL on activated T cells is
      differentially controlled.

PMID- 8757948
TI  - Role of HLA-B*5101 binding nonamer peptides in formation of the HLA-Bw4 public
      epitope.
AB  - HLA-Bw4 is one of two HLA-B public epitopes which are discriminated by specific
      alloantisera and mAb. It is believed that the 77-83 of HLA-B molecules form the
      Bw4 epitope recognized by specific antibodies. This epitope is also recognized by
      NKB1 receptors on NK cells. We investigated the role of a peptide bound to HLA-B
      molecules on the formation of the Bw4 epitope recognized by two HLA-Bw4-specific
      mAb, TU109 and TU48, which recognized the difference of the Bw4 epitope among HLA
      B52, -B52 and -B53. Recognition of the HLA-B*5101-peptide complex by these mAb
      was examined using a panel of HLA-B*5101 binding nonamer peptides. The sequence
      of HLA-B*5101 binding peptides has a minimum influence on the binding of TU48 mAb
      to HLA-B*5101 molecules. In contrast, the binding of TU109 mAb to HLA-B*5101
      molecules was critically influenced by the sequence of a peptide bound to HLA
      B*5101 molecules. TU109 mAb did not recognize HLA-B*5101 binding peptides
      carrying small or negatively charged residues at P8. The results were confirmed
      by a panel of mutant peptides at P8. Taken together, these results indicate that
      a positively charged or neutralized side chain of P8 is critical for the epitope
      formation of Bw4 recognized by this mAb.

PMID- 8757949
TI  - The nature of cryptic epitopes within the self-antigen myelin basic protein.
AB  - Mechanisms that allow potentially autoreactive T cells to escape central
      tolerance and persist in the peripheral lymphoid organs of healthy individuals
      are poorly defined. It has been proposed that such cells are specific for
      epitopes which normally are not well presented to the immune system or, in other
      words, are cryptic. We have used synthetic peptides to define potential T cell
      epitopes within the N-terminal portion of myelin basic protein (MBP). These were
      defined in terms of their relative affinity for the MHC-restriction element I-Au
      and their ability to activate T cells in mice of the H-2(u) haplotype. Three
      epitopes were identified, one of which corresponded to the known dominant N
      terminal epitope (Ac1-9). The other two epitopes (9-20 and 5-20) bound to their
      MHC-restriction element with relatively high affinity but were cryptic, as
      defined by the poor response to these epitopes following immunization with intact
      MBP. Even the longer of these two epitopes did not induce autoimmune
      encephalomyelitis in H-2(u) mice. These results demonstrate that antigen
      processing can control both the induction of and effector function of
      autoreactive T cells, and is therefore a principal mechanism involved in limiting
      the autoreactive T cell repertoire.

PMID- 8757950
TI  - Normal D-JH rearranged products of the IgH gene in SCID mouse bone marrow.
AB  - SCID mice are profoundly immunodeficient, resulting from an inability to carry
      out the V(D)J recombination reaction during both B cell and T cell development.
      Recently, however, it was revealed that normal rearrangement frequently did occur
      in the TCR delta and gamma chain loci in the SCID thymus. To evaluate whether the
      normal rearrangement occurring in SCID is a T-cell-specific phenomenon, we
      directly cloned using PCR the DQ52-JH2 and DFL16.1-JH2 rearranged segments of the
      IgH gene from SCID bone marrow. The subsequent analysis revealed that normal
      V(D)J recombination occurred in a significant number of the analyzed clones. By
      quantitative Southern hybridization it was shown that the quantity of normal DQ52
      JH2 joints existing in the SCID bone marrow is approximately 4-7% that in normal
      bone marrow. D-JH rearrangement in SCID mice and normal mice differs in the
      frequency of nucleotide insertion (N insertion). Although most of the normal
      mouse clones exhibited N insertion in the D-JH rearrangement, in SCID mouse
      clones N insertion was identified in only a few D-JH rearrangements. Furthermore,
      in several normal rearranged clones, the recombination occurred at the short
      homologous sequence. These observations suggest that the V(D)J recombination of
      IgH normally occurs at the early stage of SCID B cell development, just as TCR
      gene rearrangement occurs during SCID T cell development. Furthermore, the
      features of rearranged products isolated from SCID bone marrow cells were
      remarkably similar to those from leaky SCID mice.

PMID- 8757951
TI  - Preferential requirement of CD3 zeta-mediated signals for development of immature
      rather than mature thymocytes.
AB  - Antigen recognition signals by the TCR are transduced through activation motifs
      present in the cytoplasmic region of CD3 chains. In vitro analysis has suggested
      that the CD3zeta chain mediates different signals from other CD3 chains. To
      analyze the in vivo function of CD3zeta-mediated signals for T cell development,
      mice expressing a mutant CD3zeta chain lacking all the activation motifs were
      generated by introducing the transgene into zeta-knockout mice. Mature CD4(+)
      single-positive (SP) thymocytes in these mice were greater in number than in zeta
      deficient mice, and the promoted differentiation was indicated by the changes of
      CD69 and HSA phenotypes. We found that even in the absence of activation motifs
      in CD3zeta, these mature cells became functional, being able to induce Ca2+
      mobilization and proliferation upon stimulation. On the other hand, CD4(-)CD8(-)
      double-negative (DN) thymocytes, most of which were arrested at the CD44(
      )CD25(+) stage similarly to those in zeta-deficient mice, could not be promoted
      for differentiation into CD4(+)CD8(+) double-positive thymocytes in these mice in
      spite of the fact that the expression of the transgene in DN thymocytes was
      higher than that of zeta in wild-type mice. These results demonstrate the
      preferential dependence of the promotion of development and/or expansion of DN
      thymocytes rather than mature thymocytes upon the activation signals through the
      zeta chain and suggest differential requirements of TCR signaling for mature SP
      and immature DN thymocyte developments in vivo.

PMID- 8757952
TI  - Defects of somatic hypermutation and class switching in alymphoplasia (aly)
      mutant mice.
AB  - The alymphoplasia (aly) mutation of mice causes the systemic absence of lymph
      nodes, Peyer's patches and well-defined lymphoid follicles in the spleen. We
      found that antibody responses are elicited, albeit weakly, to either T cell
      dependent or T cell-independent antigen by aly/aly mutants. However, isotype
      switching was defective. The T cell-dependent immune response was not elicited in
      splenectomized aly/aly mice. Neither hypermutation nor germinal center formation
      was observed in aly/aly mice. These results suggest that T-B collaboration
      requires either lymph nodes or spleen, and that hypermutation and affinity
      maturation depend on germinal center formation.

PMID- 8757953
TI  - Alterations in CD4 dependence accompany T cell development and differentiation.
AB  - Several studies have indicated that the necessity for co-receptor engagement
      during T cell activation depends on the avidity of the TCR-MHC interaction under
      investigation. Using thymocytes, naive T cells and a long-term T cell line
      isolated from 2B4 TCR transgenic mice, we have examined the role of the CD4 co
      receptor on cells expressing the identical TCR at multiple stages of T cell
      maturation. When anti-CD4 Fab fragments were used to block CD4-MHC class II
      interactions, we found decreasing CD4 dependence as T cells matured. As a second
      approach to examining the role of the CD4 co-receptor, we generated I-Ek mutants
      defective in CD4 interactions. In the course of this study, we identified a new
      potential site for CD4 interaction in the beta1 domain of I-Ek. The new beta1
      mutation and a mutation in the previously described CD4 binding site in the beta2
      domain both interfere with stimulation of 2B4 thymocytes, but not mature T cells.
      Together these data demonstrate that the role of the CD4 co-receptor depends on
      the state of maturation of the T cell.

PMID- 8757954
TI  - Induction of T cell responses to the invariant chain derived peptide CLIP in mice
      immunized with the group 1 allergen of house dust mite.
AB  - In this study we demonstrate that immunization of H-2(b) mice with the allergen
      Der p 1 induces MHC class II restricted T cells that proliferate to residues 15
      29 of Der p 1 (p15-29) and to the murine MHC class II-associated invariant chain
      derived peptide (CLIP). T cells from naive H-2(b) mice and those immunized with
      murine CLIP fail to respond to either CLIP or p15-29. T cell lines and clones
      reactive with p15-29 strongly proliferate in response to splenic antigen
      presenting cells (APC) from normal H-2(b) mice but show reduced proliferation to
      APC from invariant chain deficient mice. Furthermore, T cells isolated from Der p
      1 primed mice and expanded on H-2(b) spleen cells in the absence of the p15-29
      epitope retained specificity for both p15-29 and CLIP, suggesting that naturally
      presented self components can act as mimetic peptides and may maintain T cell
      memory to foreign antigens.

PMID- 8757955
TI  - Primary porcine endothelial cells express membrane-bound B7-2 (CD86) and a
      soluble factor that co-stimulate cyclosporin A-resistant and CD28-dependent human
      T cell proliferation.
AB  - Increasing evidence suggests that endothelial cells can directly activate
      syngeneic, allogeneic and xenogeneic T cells. In this study we demonstrate that
      unstimulated, paraformaldehyde-fixed primary porcine aortic endothelial cells
      (PAEC) and microvascular endothelial cells (PMVEC) can provide co-stimulation for
      human T cell IL-2 secretion and proliferation. EC-mediated co-stimulation has
      both cyclosporin A (CsA)-sensitive and CsA-resistant components. The CsA
      resistant component is completely suppressed either by blocking with anti-CD28
      F(ab) fragments or CTLA-4-Ig. Northern blot analysis of unstimulated PAEC and
      PMVEC with porcine-specific probes reveals constitutive expression of B7-2 mRNA
      while B7-1 message was not detected. hCTLA-4-Ig and anti-B7-2 mAb
      immunoprecipitates a single 79 kDa PMVEC surface protein. Surprisingly, PMVEC
      conditioned media also has soluble co-stimulatory activity that is blocked by
      anti-CD28 F(ab) fragments or anti-B7-2 mAb. These findings demonstrate that
      primary unstimulated porcine EC can co-stimulate CsA-resistant human T cell
      proliferation through binding of membrane bound, constitutively expressed EC B7-2
      (CD86) to human T cell CD28, providing one of the first demonstrations of
      functional B7-2 on cells outside the immune system. In addition, PMVEC secrete or
      shed a soluble factor that mediates CD28-dependent human T cell proliferation,
      demonstrating the existence of soluble mediators of CD28 activation.

PMID- 8757956
TI  - An anti-CD2 mAb induces immunosuppression and hyporesponsiveness of CD2+ human T
      cells in vitro.
AB  - We describe here the potent specific immunosuppression obtained in vitro by LO
      CD2a, a rat mAb directed against the human CD2 molecule. Addition of low dose LO
      CD2a (40 ng/ml) at the time of mixed lymphocyte culture (MLC) initiation inhibits
      80% of the proliferation and, more impressive, addition of the mAb 4 days after
      culture initiation at a similar concentration still suppresses 50% of the MLC.
      When responder T cells previously treated with LO-CD2a are challenged a second
      time by the same donor or third party allogeneic cells, hyporesponsiveness occurs
      in both cases, although reactivity to T cell mitogenic stimulation persists.
      Finally, the low production of cytokines such as tumor necrosis factor-alpha and
      IFN-gamma after incubation of human T cells with LO-CD2a suggests the absence of
      T cell activation. These results demonstrate that LO-CD2a mAb has a significant
      immunosuppressive effect and induces hyporesponsiveness in vitro, thereby
      suggesting potential efficacy in vivo for the treatment of acute rejection and
      for the induction of tolerance in allotransplantation.

PMID- 8757958
TI  - Memory TCR repertoires analyzed long-term reflect those selected during the
      primary response.
AB  - Normal T cell repertoire selection and evolution in antigen-specific responses is
      poorly understood. We have recently described an MHC class I-restricted response
      characterized by an overwhelming expansion of CD8 cells expressing a Vbeta10 TCR,
      thus allowing the identification of antigen-selected cells directly ex vivo. Our
      present strategy to follow the overall TCR repertoire selection was to monitor
      the expression of a particular TCR alpha chain (Valpha8) on antigen-selected
      Vbeta10(+) cells by four-color flow cytometry. We demonstrate that while there is
      substantial variation among the responder mice in Valpha8 usage, the repertoires
      of individual animals remain relatively stable over long periods of time (>1
      year), with or without repeated antigenic challenge. Thus if any evolution of
      this response occurs upon re-exposure to antigen, it would appear not to skew the
      TCR repertoire established during the primary response.

PMID- 8757957
TI  - Differential expression of CD22 (Lyb8) on murine B cells.
AB  - Previous studies have established the distribution, biochemistry and functional
      attributes of human CD22, a B cell-restricted glycoprotein. Recently, molecular
      cloning of the murine CD22 equivalent revealed this molecule to be the same as
      the previously described Lyb8 alloantigen. Using the anti-Lyb8 mAb Cy34.1.2, the
      present report documents the expression patterns of CD22 within the murine B cell
      compartment. The results demonstrate that in the bone marrow, murine CD22 is
      absent on the surface of pro-B cells, pre-B cells and newly emerging IgM+ B
      cells. CD22 is present at a low density on immature IgMhi B cells and fully
      expressed on mature recirculating B cells. In the periphery, murine CD22 is
      expressed at mature levels on all B cell subsets including follicular, marginal
      zone, B1 and switched B cells. Further studies showed CD22 to be retained on
      activated murine B cells for extended periods. Finally, in combination with CD23
      and heat stable antigen, CD22 can be used to delineate the immature splenic B
      cells, and distinguish them from follicular and marginal zone cells. Together,
      the results demonstrate murine CD22 to be a useful pan marker for all mature B
      cell subsets.

PMID- 8757959
TI  - S-adenosylhomocysteine as a physiological modulator of Apo-1-mediated apoptosis.
AB  - APO-1/Fas (CD95) is a member of the tumor necrosis factor/nerve growth factor
      receptor superfamily and mediates apoptosis in various cell types. Here we show
      that L929 cells, expressing human APO-1 treated with agonistic antibodies (anti
      APO-1), elicit an early and transient increase of S-adenosylhomocysteine
      (AdoHcy), a potent inhibitor of S-adenosylmethionine (AdoMet)-dependent
      methylation reactions. In contrast, anti-APO-1 did not induce an AdoHcy increase
      in L929-APO-1 Delta4 cells expressing a C-terminally truncated APO-1 lacking part
      of the 'death domain' known to be required for the transduction of apoptotic
      signals. Addition of adenosine and D, L-homocysteine also led to an increase of
      cellular AdoHcy thus enhancing anti-APO-1-induced killing of L929-APO-1 cells.
      Treatment with anti-APO-1 also induced release of arachidonic acid from
      phospholipids: this effect was augmented by elevated levels of AdoHcy. In
      contrast, AdoHcy had only a minor effect on anti-APO-1-mediated DNA
      fragmentation. These findings suggest that AdoHcy functions as a physiological
      modulator of APO-1-mediated cell death in L929 cells and enhances anti-APO-1
      induced cell killing at least partially by acting via the phospholipase A2
      pathway.

PMID- 8757960
TI  - Elevated expression levels of an Ig transgene in mice links the IgH 3' enhancer
      to the regulation of IgH expression.
AB  - To delineate the role of the IgH 3' enhancer in the regulation of Ig heavy (IgH)
      chain gene expression, mice harbouring rearranged IgH transgenes, with (PSVmu3)
      and without (PSVmu1) this element, were produced. RNA and protein analysis from
      the different transgenic lines revealed a 5- to 7-fold increase in the expression
      level of the transgene containing the IgH 3' enhancer. This difference is also
      reflected at the protein level in hybridomas generated from the two transgenic
      lines. The elevation of transgene Ig expression in the PSVmu3 lines is restricted
      to activated B lymphocytes, an observation which is further supported by the
      ability of this transgene to be reactivated upon immunization. Interestingly,
      although the up-regulation of transgene expression in PSVmu3 animals is
      considerably higher in comparison to the PSVmu1 animals, a significant response
      is still observed in the PSVmu1 mice. We speculate therefore that the IgH locus
      is subject to transcriptional modification in late B cell development. Our data
      suggest that both the Emu enhancer and the IgH 3' enhancer can up-regulate
      transgene Ig expression, but the presence of the 3' enhancer results in elevated
      levels of transgene Ig production. It therefore appears that the expression level
      of IgH genes is subject to transcriptional modification during B cell
      development. Additional control elements are most likely required for optimal Ig
      expression, since our expression data from the transgene in PSVmu3 animals are
      incompatible with endogenous Ig levels. The recent identification of additional
      enhancer elements in the far 3' end of the IgH locus supports this possibility.
      The data presented here provides a sound basis for the production of high levels
      of mAb, possibly tailored to suit the needs of the researcher.

PMID- 8757961
TI  - Lck dependence of signaling pathways activated by gamma-irradiation and CD3
      epsilon engagement in RAG-1(-/-)-immature thymocytes.
AB  - The src family tyrosine kinase, Lck, transduces signals from the pre-TCR complex
      which regulate the development and expansion of CD4/CD8 double-positive (DP)
      thymocytes from CD25(+) CD4/CD8 double-negative progenitors. We and others have
      recently shown that sublethal gamma-irradiation bypasses the need for TCRbeta
      expression to promote the development and expansion of DP thymocytes in scid or
      recombinase-activating gene (RAG)-deficient mice. Here we demonstrate that gamma
      irradiation activates an Lck-dependent signaling process in immature thymocytes
      similar to that initiated physiologically by the pre-TCR complex.

PMID- 8757962
TI  - Kupffer cell-mediated cytotoxicity against hepatoma cells occurs through
      production of nitric oxide and adhesion via ICAM-1/CD18.
AB  - Rat Kupffer cell (KC)-mediated cytotoxicity against both the syngeneic hepatoma
      cell line AH70 and hepatocytes was evaluated by changes in mitochondrial
      function, and the possible role of ICAM-1/CD18 in the interaction between the
      cells was studied. Rhodamine 123 fluorescence, a marker of the mitochondrial
      membrane potential, decreased in AH70 cells after co-culture with CK, while that
      in hepatocytes was unchanged by co-culture. This decrease was blocked by anti
      ICAM-1 anti-CD18 and the inhibition of nitric oxide synthesis. Cytometric studies
      demonstrated that ICAM-1 expression on AH70 cells increased after addition of IFN
      gamma, IL-1beta, tumor necrosis factor (TNF)-alpha or KC, while in hepatocytes
      ICAM-1 was not increased. Anti-ICAM-1 pretreatment inhibited the increase in ICAM
      1 expression and the decrease in rhodamine 123 fluorescence on AH70 cells after
      co-culture with KC. CD18 on KC was increased only after co-culture with AH70. TNF
      alpha but not IFN-gamma was detected in the supernatant of co-culture between KC
      and AH70 cells, and this production was partially inhibited by anti-ICAM-1 and
      anti-CD18. The activity of inducible nitric oxide synthase in Kupffer cells and
      the levels of nitrites and nitrates in the co-culture supernatant increased over
      time, and this increase was attenuated either by addition of NO synthesis
      inhibitors, anti-ICAM-1 or anti-CD18. These results indicate that the rat KC
      causes mitochondrial dysfunction in cancer cells via the production of NO and
      cell-to-cell adhesion via ICAM-1/CD18 has an important role in this cytotoxic
      process.

PMID- 8757963
TI  - Role of oxidative damage and IL-1 beta-converting enzyme-like proteases in Fas
      based cytotoxicity exerted by effector T cells.
AB  - The implication of oxidative damage and/or intact mitochondrial function in
      physiological Fas-based cytotoxicity has been tested using the cytolytic
      hybridoma d11S and the CD8(+) CTL clone KB5.C20, previously stimulated to express
      Fas ligand (FasL) on their surface, as effectors and U937 or U937-rho0 cells
      (depleted of mitochondrial DNA) as targets. Immobilized anti-Fas mAb, which
      induced death of U937 cells, inhibited the growth of U937-rho0 cells but without
      inducing cell death. By contrast, FasL-expressing effectors readily killed both
      targets, with induction of DNA fragmentation, in 20 h assays. These results
      demonstrate the lack of involvement of mitochondrial-derived free radicals and/or
      intact mitochondrial function in physiological Fas-based cytotoxicity.
      Supplementation of Fas-sensitive cells (Jurkat, U937, L1210Fas) with a
      polyunsaturated fatty acid, which induces cell death through the generation of
      lipid free radicals, resulted in the potentiation of Fas-based cytotoxicity. This
      potentiating effect, but not Fas-based cytotoxicity itself, was eliminated by the
      physiological antioxidant vitamin E. On the other hand, the IL-1beta-converting
      enzyme (ICE)-like protease tetrapeptide inhibitor Ac-YVAD-cmk partially inhibited
      Fas-based cytotoxicity, while the specific inhibitor of CPP32/Yama Ac-DEVD-CHO
      was a much more effective inhibitor of Fas-induced apoptosis. It was concluded
      that Fas-induced cytotoxicity was clearly dependent on ICE-like protease
      activation, and especially on that of CPP32 in Fas-sensitive cells, including
      mitochondrial DNA-depleted ones.

PMID- 8757964
TI  - Molecular control of erythroid differentiation.
AB  - The number of circulating red cells is regulated by the daily balance between two
      processes: the destruction of the old red cells in the liver and the generation
      of new cells in the bone marrow. The process during which hematopoietic stem
      cells generate new red cells is called erythropoiesis. This article describes the
      most recent advances in molecular and cellular biology which have allowed the
      identification of the molecular mechanisms involved in the process of erythroid
      differentiation. It reviews the cellular compartments involved in the process,
      what is known on how these cells respond to erythroid specific growth factors and
      how the cells progressively activate specific transcription factors in order to
      express genes involved in the establishment of the erythroid phenotype.

PMID- 8757965
TI  - Cytogenetic and molecular genetic studies on Indian patients with chronic
      lymphocytic leukemia.
AB  - This is the first cytogenetic and molecular genetic study to find any specific
      genetic abnormalities in Indian patients with chronic lymphocytic leukemia (CLL).
      Cytogenetic studies on 18 patients indicated that their karyotypes were
      relatively simple and trisomy 12 was seen on karyotype evolution in one patient.
      Fluorescence in situ hybridization (FISH) revealed abnormal clones of trisomy 12
      in nine cases and RB gene deletion in 14 of the 29 cases analyzed. Three patients
      had both clones. Immunoglobulin genes were rearranged in all the cases and TCR
      beta in none of the 18 cases Southern blotted. BCL-1 was rearranged in one case.
      No rearrangement of BCL-2 gene was seen in any case. Genetic changes in Indian
      CLL were more similar to Western CLL than to Japanese CLL, even though India is
      supposed to be a low incidence area. Therefore, factors (such as HLA and other
      genetic markers) other than these routine parameters must be studied to explain
      the low incidence of CLL in India.

PMID- 8757966
TI  - Suppression of humoral immunity by monoclonal antibody to CD79b, an invariant
      component of antigen receptors on B lymphocytes.
AB  - CD79b is an invariant component of antigen receptors on B lymphocytes. Previous
      data have suggested that monoclonal antibody (mAb) to CD79b would introduce
      negative signals into B lymphocytes and suppress humoral immunity. We tested this
      hypothesis in this study using in vitro assay systems, and revealed that anti
      CD79b mAb effectively suppressed the antibody response to a T-cell dependent
      antigen. The speculated mechanisms for this immunosuppression were: (i) down
      modulation of antigen receptors, (ii) inhibition of B lymphocyte differentiation,
      and (iii) induction of B lymphocyte unresponsiveness. Of these three, we
      confirmed that the first two were actually induced by anti-CD79b mAb treatment,
      whereas the in vitro system could not induce the unresponsiveness of B
      lymphocytes.

PMID- 8757967
TI  - High prevalence of B-cell monoclonality in labial gland biopsies of Japanese
      Sjogren's syndrome patients.
AB  - Patients with Sjogren's syndrome (SS) have an increased risk of developing
      malignant lymphoma. Although some clinical parameters may herald the imminent
      onset of lymphoma, few reliable markers are available to predict the progression
      to a malignant lymphoproliferative disorder. Although there are a number of
      immunological and serologic features that distinguish SS in Japanese patients, in
      common with their Western counterparts these patients also have an increased risk
      of lymphoid neoplasia. Recently we have reported finding a high prevalence (17%)
      of monoclonal immunoglobulin (Ig) heavy chain gene rearrangements in labial
      salivary gland (LSG) biopsies of Western SS using the polymerase chain reaction
      (PCR). In many cases this finding was predictive for the subsequent development
      of lymphoma. In this study LSG from 50 Japanese SS patients were examined for Ig
      heavy chain gene monoclonality using PCR to amplify the VDJ region and identified
      in 7 of 50 (14%) cases. Three patients with monoclonality in the LSG had evidence
      of lymphoma at extra-salivary gland sites. In one of these the diagnosis of
      lymphoma was made subsequent to lip biopsy. In the other two lymphoma at extra
      salivary gland sites was diagnosed prior to LSG biopsy. The results suggest that
      the prevalence of Ig heavy chain gene monoclonality in LSG of Japanese SS
      patients is similar to that in the West, and that neoplastic cells can be
      identified in LSG as a component of more widely disseminated disease.

PMID- 8757968
TI  - A sequence analysis of von Willebrand factor mRNA, gene, and pseudogene in two
      patients with von Willebrand disease type 2B, and an investigation of gene
      conversion in its gene.
AB  - We identified the point mutations in two unrelated patients with von Willebrand
      disease (vWD) type 2B using sequence analyses of the gene, pseudogene and
      messenger RNA of vWF. Both patients were determined to be heterozygotes with
      amino acid transitions of 1308 Arg-->Cys in Case 1 and 1316 Val-->Met in Case 2.
      Moreover, we also found single base transitions 7541 A-->G in intron 27 of the
      active gene, and 7642 A-->G, which thus destroyed the Kpn 1 site, in its
      pseudogene in both cases. Since these mutations represented changes in the base
      between the gene and its pseudogene, we studied the presence of gene conversion
      in exon 28 of vWF gene to clarify its pathological role. Using RT-PCR and an
      allele-specific restriction enzyme analysis, we identified no gene conversions in
      this region in four other patients with vWD, 25 normal subjects and one cell
      line, MEG01. Based on these findings, gene conversion in the vWF gene is not
      considered to be a frequent phenomenon in either vWD patients or normal subjects.

PMID- 8757969
TI  - Hereditary partial deficiency of plasminogen activator inhibitor-1 associated
      with a lifelong bleeding tendency.
AB  - We report a family with a partial deficiency of plasminogen activator inhibitor-1
      (PAI-1). The affected family members had had lifelong bleeding episodes, such as
      rebleeding after tooth extraction and trauma. This bleeding tendency in the
      propositus was autosomally transmitted from grandfather to son. The
      characteristic abnormalities of fibrinolysis in the patients were shortened
      eugloblin lysis time, low PAI activity with low antigen levels of plasminogen
      activator inhibitor-1 in plasma and serum. Furthermore, plasma 'active PAI' which
      indicates the quantity of plasminogen activator inhibitor-1 bound with
      plasminogen activator added was very low in these patients. These parameters were
      markedly low after the venous occlusion test. Moreover, two of the affected
      members had a much lower level of platelet PAI-1 than the normal controls.
      Tranexamic acid (Transamine) was useful to control bleeding in these patients.

PMID- 8757970
TI  - Acquired sideroblastic anaemia induced by a copper-chelating agent.
AB  - Acquired sideroblastic anaemia may be related to drugs and other chemicals that
      inhibit the activity of mitochondrial enzymes involved in haem synthesis. We
      report a case of secondary acquired sideroblastic anaemia following
      administration of triethylene tetramine dihydrochloride (trientine), a second
      line copper-chelating agent used in the treatment of Wilson's disease. The
      anaemia improved after dose reduction of trientine. The mechanism of induction of
      sideroblastic anaemia in this case is unclear, but trientine does not appear to
      alter the function of two key mitochondrial haem enzymes, and may instead act
      directly on mitochondrial iron metabolism.

PMID- 8757971
TI  - Philadelphia chromosome-negative cells with trisomy 8 after busulfan and
      interferon treatment of Ph1-positive chronic myelogenous leukemia.
AB  - A 48-year-old Japanese man with Philadelphia chromosome (Ph1)-positive chronic
      myelogenous leukemia (CML) was treated with busulfan followed by interferon-alpha
      (IFN-alpha). Ten months after IFN-alpha treatment, Ph1(-) cells with trisomy 8
      were detected by the conventional banding technique and fluorescence in situ
      hybridization (FISH) analysis. Add(Y)(q12) was also found in Ph1(-) cells with
      trisomy 8. Although Ph1(+) cells disappeared after the treatment with IFN-alpha,
      Ph1(-) cells with trisomy 8 did not. We summarize four previous case reports of
      Ph1(+) CML developing Ph1(-) cells with trisomy 8. All four patients had received
      busulfan and IFN-alpha. These drugs may be related to the ontogenesis of Ph1(-)
      cells with trisomy 8, but the significance of Ph1(-) cells with trisomy 8 is not
      known, and further observation is needed.

PMID- 8757972
TI  - Potyviral HC-Pro: a multifunctional protein.

PMID- 8757973
TI  - Switches in the mode of transmission select for or against a poorly aphid
      transmissible strain of potato virus Y with reduced helper component and virus
      accumulation.
AB  - A poorly aphid-transmissible potato virus Y (PVY-PAT) variant emerged after
      several cycles of mechanical transmission of an initially aphid-transmissible
      (AT) isolate. Sequence analysis of the N-terminal region of the helper component
      proteinase (HC-Pro) gene revealed a Lys to Glu change at a position previously
      found to abolish the HC-Pro aphid transmission activity in several potyviruses.
      Two cycles of aphid transmission allowed the virus population to evolve towards
      an AT form (PVY-ATnew) where a Glu to Lys change was observed. PVY-PAT produced
      lower amounts of coat protein and the accumulation of its HC-Pro in infected
      plants decreased from 7 to 28 days post-inoculation, as compared to PVY-ATnew. RT
      PCR and restriction analysis showed that the two virus populations co-existed in
      the PVY-AT isolate and that the AT form was counter-selected during mechanical
      transmission. These observations suggest that the Lys to Glu substitution leads
      to decreased stability of HC-Pro resulting in poor transmissions by aphids, and
      further strengthen the idea that HC-Pro is involved in the accumulation of
      potyvirus in infected plants.

PMID- 8757974
TI  - Assembly of virus-like particles in insect cells infected with a baculovirus
      containing a modified coat protein gene of potato leafroll luteovirus.
AB  - DNA encoding the coat protein (P3) of a Scottish isolate of potato leafroll virus
      (PLRV) was inserted into the genome of Autographa californica
      nucleopolyhedrovirus (AcNPV) such that the coat protein was expressed either in
      an unmodified form or with the addition of the amino acid sequence
      MHHHHHHGDDDDKDAMG at the N terminus (P3-6H). Insect cells infected with these
      recombinant baculoviruses accumulated substantial amounts of P3 and P3-6H. P3
      could not be recovered from cell extracts unless it was denatured in SDS but a
      proportion of the P3-6H was recoverable in a soluble form in non-denaturing
      conditions. Immunogold labelling of sections of infected cells showed that P3
      accumulated in nuclei in large amorphous bodies. In contrast, although much of
      the P3-6H also accumulated in nuclei, it formed virus-like particles (VLP) which
      were often grouped in close-packed, almost cystalline arrays. When electron
      microscope grids coated with antibodies to PLRV were floated on cell extracts
      containing P3-6H, VLP were trapped which were indistinguishable from PLRV
      particles trapped from extracts of PLRV-infected plants. The VLP co- sedimented
      in sucrose gradients with PLRV particles which suggests that the VLP contained
      RNA. VLP collected from sucrose density gradient fractions contained protein
      which reacted with nickel chelated to nitrilotriacetic acid, a histidine-specific
      reagent. Cells infected with either recombinant baculovirus also synthesized a
      protein, with an Mr of about 17000, which was shown to be the translation product
      of the P4 gene which is in the +1 reading frame within the coat protein gene.
      This protein was also found in the nuclear fraction of infected cells but was
      more readily soluble than was P3.

PMID- 8757975
TI  - High resolution analysis of the readthrough domain of beet necrotic yellow vein
      virus readthrough protein: a KTER motif is important for efficient transmission
      of the virus by Polymyxa betae.
AB  - The 5'-terminal cistron of beet necrotic yellow vein furovirus RNA 2 encodes the
      21 kDa major viral coat protein and terminates with an amber stop codon which can
      undergo suppression to give rise to a 75 kDa readthrough (RT) protein referred to
      as P75. P75 is a minor component of virions and the 54 kDa RT domain following
      the coat protein sequence is important both for virus assembly and transmission
      by the fungal vector Polymyxa betae. To better define the regions of the RT
      domain involved in these two steps, RNA 2 transcripts encoding different in-frame
      RT domain deletion mutants were tested for their ability to form virions when
      inoculated to plants with the other viral RNAs and to be fungus-transmitted. All
      deletions in the N-terminal half of the RT domain interfered with virus assembly
      and partially or completely inhibited fungus transmission. A 4 1 1 nucleotide
      deletion within the C-terminal half of the RT domain did not inhibit assembly but
      blocked fungus transmission of the virus. Alanine scanning mutagenesis within the
      aforesaid 4 1 1 nucleotide subdomain identified a peptide motif (KTER) which is
      important for the fungus transmission process.

PMID- 8757976
TI  - Horseradish curly top virus is a distinct subgroup II geminivirus species with
      rep and C4 genes derived from a subgroup III ancestor.
AB  - The complete nucleotide sequence (3080 nt) of an infectious DNA clone derived
      from the geminivirus horseradish curly top virus (HrCTV) has been determined. The
      relationship of HrCTV to other geminiviruses was examined using dot matrix plots
      of nucleotide sequence similarities, and by phylogeny of predicted amino acid
      sequences of individual ORFs based upon parsimony or neighbour-joining methods.
      These analyses indicate that the V1 and V2 virion sense ORFs of HrCTV are most
      closely related to, yet distinct from, the corresponding ORFs of the subgroup II
      geminivirus beet curly top virus (BCTV). HrCTV also encodes a third virion sense
      ORF (V3) which is similar (72-74 percent amino acid identity) to the BCTV V3 ORF;
      however, the HrCTV V3 ORF has diverged in sequence to a greater extent relative
      to that observed among isolates of BCTV (98-100% amino acid identity). The HrCTV
      genome encodes only three complementary sense ORFs (Cl, C2 and C4) and lacks a C3
      ORF which is conserved among all other subgroup II and III geminiviruses
      characterized to date. Although the neighbour-joining analysis indicated that the
      HrCTV C2 ORF was distantly related to the C2 ORF of BCTV, the predicted amino
      acid sequence deduced from the HrCTV C2 ORF lacks the characteristic zinc-finger
      domain present in the transcriptional activating protein (TrAP) encoded by the
      subgroup III ORF AC2, which is also retained within the TrAP-related product of
      the BCTV C2 ORF. Surprisingly, the rep and C4 proteins encoded by HrCTV share a
      closer phylogenetic relationship to the corresponding proteins of the subgroup
      III geminivirus squash leaf curl virus (SLCV) than to BCTV. These results suggest
      that the HrCTV genome may have arisen by a recombination event between a BCTV
      like subgroup II virus ancestor and an SLCV-like subgroup III virus ancestor.
      Possible mechanisms that may explain recombination events among geminiviruses are
      discussed.

PMID- 8757977
TI  - Expression of polydnavirus genes under polydnavirus promoter regulation in insect
      larvae infected with baculovirus recombinants.
AB  - We have evaluated the use of baculoviruses to deliver Campoletis sonorensis
      polydnavirus (CsPDV) genomic DNA into lepidopteran larvae to facilitate the
      identification of functional CsPDV genes. Genomic fragments consisting of
      regulatory (promoter) and coding sequences for two CsPDV genes (VHv1.1 and
      WHv1.6) were used to generate CsPDV-baculovirus recombinants and evaluate the
      expression of genes under the regulation of the CsPDV promoters. Northern blot
      and primer extension studies established that CsPDV genes were expressed under
      the control of their own promoters in these CsPDV-baculovirus recombinants.
      Transcripts were detected as early as 4 h post-infection indicating that temporal
      activity of CsPDV promoters was retained. The VHv1.1 gene product as expressed
      from CsPDV-baculovirus recombinants was identical in size and in functional
      properties to that produced in CsPDV-infected insects. CsPDV-baculovirus
      recombinants may be useful for the screening and characterization of polydnavirus
      genes with functional activities that can only be evaluated in insect larvae.

PMID- 8757978
TI  - Unimpaired function of a naturally occurring C terminally truncated vif gene
      product of human immunodeficiency virus type 1.
AB  - In approximate 10 percent of natural human immunodeficiency virus 1 (HIV-1) vif
      gene populations, sequences of shortened vif open reading frames with premature
      stop codons have been found. Here we report the functional analysis of two
      patient-derived vif genes. Vif45-2 encodes a C terminally truncated Vif protein
      of only 173 instead of 192 amino acids and additionally contains several rare
      amino acid substitutions which are in part shared by vifA65-5. HIV-1 pNL4-3
      derived recombinant A45-2 and A65-5 virions were fully infectious in H9 cells and
      human PBMC, both known to be non-permissive for vif-defective HIV-1. Furthermore,
      A45-2 virions produced in primary human monocyte-derived macrophages were
      infectious for MT-4 cells. This study unequivocally demonstrates that the C
      terminal region (19 amino acids) of the Vif protein is dispensable for Vif
      function in the in vitro cell culture systems employed. Additionally, we
      investigated whether the Vif protein might be phosphorylated in vivo and obtained
      no evidence for this.

PMID- 8757979
TI  - Varying temperature-dependence of post-attachment neutralization of human
      immunodeficiency virus type 1 by monoclonal antibodies to gp 120: identification
      of a very early fusion-independent event as a neutralization target.
AB  - Neutralization of human immunodeficiency virus type 1 by adding antibody after
      the virus has attached to the host cell (post-attachment neutralization:PAN) was
      investigated using three rat monoclonal antibodies (MAbs) directed against the
      outer domain of the membrane protein, gp 120. Two of the MAbs are specific for
      the CD4-binding site region and one for the V3 loop. MAb ICR39.13g (CD4-binding
      site region-specific; IgG2b) effected PAN efficiently at temperatures from 4 to
      35 degree C. MAb ICR41.1i (V3 loop-specific; IgG2c) effected PAN only at
      temperatures of 24 degree C and below. This suggests that its V3 epitope is
      masked by a change in gp 120 which occurs at temperatures > or = 26 degree C, or
      that the virion function which is inhibited by ICR41.1i and is responsible for
      neutralization has already operated at > or = 26 degree C. Resistance to
      neutralization by ICR41.1i occurred within 20 min of shifting the temperature up
      to 35 degree C. Finally, MAb ICR39.3b (CD4-binding site region-specific; IgG2b)
      did not give PAN at any temperature, indicating that neutralization can only
      occur if this MAb binds virus before it attaches to the cell. Thus, these studies
      identify at least one novel fusion-independent event, the neutralization target
      of a V3 MAb, which occurs very early in the initial stages of virus-cell
      interaction.

PMID- 8757980
TI  - Antigenicity of truncated forms of the human immunodeficiency virus type 1
      envelope glycoprotein.
AB  - Chinese hamster ovary (CHO) cell lines secreting a series of truncated forms of
      human immunodeficiency virus type 1 (HIV-1) IIIB (clone BH10) gp12O were
      assembled. Using purified glycoproteins, we demonstrated the functional and
      structural integrity of these truncates by their reactivity with both sCD4 and
      anti-gp 120 monoclonal antibodies (MAbs). Deletion of the Vl, V2 and V3 regions
      had minimal effects on CD4 binding, but deletion of the NH2 terminus affected the
      folding of the truncated molecule. Deletion of either V1/V2 or V1/V2/V3 regions
      led to enhanced recognition by some, but not all, MAbs mapping to the CD4 binding
      site. In contrast, deletion of the V1/V2 regions had no effect on the ability of
      V3-specific MAbs to bind to the truncate. These results support the use of
      truncated forms of gp12O as components of potential HIV vaccines.

PMID- 8757981
TI  - Replication kinetics and cell tropism of an immunosuppressive feline leukaemia
      virus.
AB  - To elucidate in vivo cell tropism and infection kinetics of an immunodeficiency
      inducing isolate of feline leukaemia virus (FeLV-FAIDS), we quantified the two
      major genotypes comprising FeLV-FAIDS [the replication-competent common form
      (clone 61E) and the replication-defective variant (clone 61C)] in lymphocyte and
      leukocyte populations from infected cats. Micromagnetic separation of cell
      subsets, virus genome-specific PCR and flow cytometry were used to demonstrate
      the following sequence of events in infected animals: (i) very early replication
      of both 61E and 61C in CD4 T cells (provirus burden 0.2 to 1 copy/cell at 2-4
      weeks post-infection); (ii) lower magnitude replication of both viruses in CD8 T
      cells and B cells during this initial phase of infection; (iii) plateauing of CD4
      cell virus burden accompanied by escalation in CD8 and B cell provirus burdens
      after 4 weeks; (iv) extensive infection of haemopoietic and circulating myeloid
      cells. FeLV-FAIDS 61E and 61C replication kinetics and lymphocyte tropisms were
      similar in blood and lymph nodes, where provirus burdens ranged from 0.15 to 1.0
      copy/cell. Moreover, virus infection was productive; 8-48 percent of blood
      lymphocytes, 35-81 percent of node lymphocytes and 53-98 percent of bone marrow
      cells expressed FeLV capsid antigen (p27 Gag). These findings suggest that the
      immunosuppressive potency of FeLV-FAIDS reflects the unique cytopathicity rather
      than unique cytotropism of its 61C (versus 61E) component.

PMID- 8757982
TI  - Characterization of the gene encoding core protein VP6 of two African
      horsesickness virus serotypes.
AB  - The genes encoding the inner core protein VP6 of African horsesickness virus
      (AHSV) serotypes 3 and 6 have been cloned and sequenced. The genes are 1169
      nucleotides in length and both encode a largely hydrophilic protein of 369 amino
      acids. The VP6 amino acid sequence is highly conserved between the two serotypes
      with an overall similarity of 95 percent. Comparison of the AHSV VP6 amino acid
      sequences with those of bluetongue virus serotype 10 VP6 revealed that it is 41
      amino acids longer with an overall amino acid identity of 29 percent. The
      similarity is mainly confined to a short but highly conserved 13 amino acid
      region at the N terminus, a short seven amino acid region at the C terminus and a
      22 amino acid region close to the C terminus. Within this last region is a
      smaller 11 amino acid region from 318 to 328 with a 91 percent similarity to the
      Rep helicase of Escherichia coli.

PMID- 8757983
TI  - Interference of reovirus strains occurs between the stages of uncoating and dsRNA
      accumulation.
AB  - Interference of wild-type reovirus growth by some temperature-sensitive (ts)
      mutant viruses under non-permissive conditions or by other wild-type isolates has
      been demonstrated; however, the stage of the virus replication cycle at which
      interference occurs has not been defined. Examination of the time-course of the
      yields of T1 Lang (T1L) dsRNA in the progeny of mixed infections of T1L with T3
      Dearing (T3D) or with a panel of T3D ts mutants at a non-permissive temperature
      revealed that interference takes place by 8-10 h post-infection and occurs prior
      to or at the same time as accumulation of reovirus dsRNA. Taken together with our
      previous results, these data indicate that interference occurs during a window
      between virus uncoating and synthesis of dsRNA in the reovirus replication cycle,
      probably at the stage of assembly of primary reovirus particles.

PMID- 8757984
TI  - Pathogenesis of an attenuated and a virulent strain of group A human rotavirus in
      neonatal gnotobiotic pigs.
AB  - Gnotobiotic (Gn) pigs were orally inoculated with Wa strain (G1P1A[P8]) human
      rotavirus (Wa HRV) serially passaged in Gn pigs (virulent) or cell culture
      (attenuated) to determine the median virus infectious dose (ID50) and to assess
      the site of infection and type and progression of morphological lesions and
      clinical responses induced by these two strains in Gn pigs. The ID50 of virulent
      Wa HRV was = or < 1 f.f.u. whereas the infectivity of attenuated Wa HRV had to be
      determined by seroconversion and was approximately 1.3 x 1O(6) f.f.u. Diarrhoea
      developed at 13 h post-inoculation (p.i.) in pigs inoculated with approximately
      1O(5) f.f.u. of virulent Wa HRV and correlated with the presence of viral antigen
      within villous epithelial cells; villous atrophy developed later at 24 h p.i. and
      correlated with peak faecal viral titres; recovery from disease correlated with
      the return of morphologically normal villi. Virus, diarrhoea and villous atrophy
      were not detected in pigs inoculated with approximately 2 x 10(8)f.f.u.
      attenuated Wa HRV although HRV-specific serum antibodies were present by 7 days
      p.i. These findings demonstrate that virulent Wa HRV infection in Gn pigs occurs
      primarily within intestinal villous epithelial cells with villous atrophy
      developing as a sequela to infection. However, factors other than villous atrophy
      appear to contribute to the early stages of HRV-associated disease expression in
      Gn pigs. The ability of the attenuated virus to elicit virus-neutralizing serum
      antibodies without disease or pathology indicates promise in the use of such
      strains for oral immunization.

PMID- 8757985
TI  - The region between the M and S genes of porcine haemagglutinating
      encephalomyelitis virus is highly similar to human coronavirus OC43.
AB  - The nucleotide sequences of the regions between the membrane and spike protein
      genes of three strains of porcine haemagglutinating encephalomyelitis virus (HEV)
      were determined. A total of 739 (HEV strain 67N) and 751 (strains NT9 and VW572)
      nucleotides were sequenced. Two ORFs, potentially encoding proteins of 12.8 and
      9.6 kDa, were identified. Pairwise comparisons with the corresponding ORFs in
      bovine coronavirus (BCV) and human coronavirus (HCV) OC43 revealed sequence
      similarities of greater than 88.5 percent at the nucleotide and 85.3 percent at
      the amino acid level for the 12.8 kDa ORF product. For the 9.6 kDa ORF product
      similarities were greater than 96.9 percent and 95.2 percent, respectively. An
      additional 12 nucleotide deletion upstream of the 12.8 kDa ORF start codon was
      found in HEV 67N compared to NT9 and VW572. These results reveal a genomic
      organization of HEV in the region analysed that is homologous to HCV OC43 but
      different from BCV.

PMID- 8757986
TI  - Molecular differences between wild-type Japanese encephalitis virus strains of
      high and low mouse neuroinvasiveness.
AB  - Japanese encephalitis (JE) virus strain P3 was highly neurovirulent and
      neuroinvasive in weanling mice whereas two other JE virus strains, SA14/USA and
      S892, were only neurovirulent. Infectivity titrations of brains and sera showed
      that P3 virus multiplied faster and reached a higher infectivity titre than S892
      virus following inoculation of viruses by the intraperitoneal (i.p.) route. The
      p.f.u./LD50 was 10(1.7) and 10(6.2) for P3 and S892 viruses respectively,
      following i.p. inoculation, while JE virus strain SA14/USA did not kill mice when
      inoculated by this route (i.e. > or = 10(6.3) p.f.u./LD50). Nevertheless, the
      genomic similarity between P3 virus and strains SA 14/USA and S892 was more than
      97.8 percent at the nucleotide level and 99 percent at the amino acid level.
      Compared with S892 and SA14/USA viruses, P3 virus had 33 and 21 amino acid
      differences, respectively. The structural protein genes of P3 virus were more
      divergent than non-structural protein genes. Nine unique amino acids were found
      in the envelope protein gene. None of these amino acid differences were shared
      with other wild-type JE virus strains. Although we cannot identify the precise
      molecular determinants of virulence of JE virus, there were no unique amino acids
      in M, NS1, NS2A, NS3, NS4A and NS4B proteins of P3 virus compared with other wild
      type viruses. Therefore, it appears that these proteins make no significant
      contribution to the high neuroinvasiveness of P3 virus. The structural proteins,
      and non-structural proteins NS2B and NS5 may be involved in increasing
      neurovirulence and neuroinvasiveness of P3 virus. P3 virus differed by several
      nucleotides in the 3' non-coding region while no nucleotide difference was found
      in the 5' non-coding region.

PMID- 8757987
TI  - Persistent infection of African buffalo (Syncerus caffer) with SAT-type foot-and
      mouth disease viruses: rate of fixation of mutations, antigenic change and
      interspecies transmission.
AB  - Transmission of a plaque-purified SAT-2 foot-and-mouth disease virus (FMDV)
      occurred erratically from artificially infected African buffaloes in captivity to
      susceptible buffaloes and cattle in the same enclosure; in some instances
      transmission occurred only after contact between persistently infected carriers
      and susceptible animals lasting a number of months. Because the rate at which
      FMDV mutations accumulated in persistently infected buffaloes was approximately
      linear (1.64 percent nucleotide substitutions per year over the region of the 1D
      gene sequenced), both buffaloes and cattle that became infected some months after
      the start of the experiment were infected with viruses that differed from the
      original clone. The nucleotide differences were reflected in significant
      antigenic change. A SAT-1 FMDV from a separate experiment inadvertently infected
      some of the buffalo in the SAT-2 experiment. The SAT-1 FMDV also accumulated
      mutations at a constant rate in individual buffaloes (1.54 percent nucleotide
      changes per year) but the resultant antigenic variation was less than for SAT-2.
      It is concluded that persistently infected buffaloes in the wild constantly
      generate variants of SAT-1 and SAT-2 which explains the wide range of genomic and
      antigenic variants which occur in SAT-1 and SAT-2 viruses in southern Africa.

PMID- 8757988
TI  - Enterovirus infection of the central nervous system of humans: lack of
      association with chronic neurological disease.
AB  - We have searched, using a sensitive nested-PCR, for enterovirus RNA in
      cerebrospinal fluid and post mortem central nervous system (CNS) tissue from
      patients with previous poliomyelitis with or without late functional
      deterioration, patients with motor neuron disease (MND), and control patients
      with other neurological disease or without neurological disease. Enterovirus RNA
      was detected in patients with previous poliomyelitis and MND, but also in control
      patients with and without neurological disease. Our results do not provide any
      evidence that such enterovirus infection is related to late functional
      deterioration in patients with previous poliomyelitis, which could be attributed
      to other medical conditions in most instances, and do not support the hypothesis
      that MND is associated with enterovirus infection of the CNS. Nucleotide sequence
      analysis of enterovirus RNA sequences detected indicated that enteroviruses
      detected were of the non-polio type.

PMID- 8757989
TI  - Interactions between the ectodomains of haemagglutinin and CD46 as a primary step
      in measles virus entry.
AB  - Recombinant soluble forms of the ectodomains of measles virus haemagglutinin (sH)
      and of its receptor CD46 (sCD46) were obtained as a purified disulphide-bonded sH
      homodimer with an apparent molecular mass of 160 kDa and a purified sCD46 monomer
      with an apparent molecular mass of 60 kDa, without detectable contamination with
      moesin. Purified sH bound to purified and immobilized sCD46 and this binding was
      specifically inhibited by sCD46 in solution. sCD46 bound to wild-type H expressed
      on the cell surface and inhibited measles virus binding to CD46-expressing cells.
      Binding of sCD46 to cell surface H was increased about twofold when measles virus
      fusion protein was coexpressed with H. sH bound to wild-type cell surface CD46
      and inhibited measles virus binding onto CD46-expressing cells. sCD46 also
      inhibited virus infection. Thus, the direct interaction between the ectodomains
      of H and CD46 is likely to be the primary event in measles virus infection.

PMID- 8757990
TI  - The immunological activity of a deletion mutant of influenza virus haemagglutinin
      lacking the globular region.
AB  - A deletion mutant of influenza virus haemagglutinin (HA; headless HA) lacking the
      globular region was expressed in CV-1 cells and detected with a monoclonal
      antibody, C179, which recognizes a conformational epitope in the middle of the
      stem region of HA and neutralizes all H1 and H2 subtypes. The cDNA coding for the
      headless HA was constructed from influenza virus A/Okuda/57 (H2N2), which was
      also used to select C179. The conformational epitope recognized by C179 was
      highly stable even after removal of the globular region. The survival rate of
      mice immunized with the headless HA and challenged with lethal influenza virus
      A/FM/l/47 (H1N1) was significantly higher than that of the control mice. The
      headless HA has the potential to induce cross-protection against influenza virus
      infection.

PMID- 8757991
TI  - Frequent occurrence of genetic reassortment between influenza C virus strains in
      nature.
AB  - Previous studies of the haemagglutinin-esterase (HE) genes of various influenza C
      isolates suggested the existence of three distinct virus lineages
      (C/Yamagata/26/81-, C/Aichi/1/81- and C/Mississippi/80-related lineages) in Japan
      in the 1980s. Here we analysed the genetic properties of three strains
      (C/Yamagata/5/92, C/Miyagi/3/93 and C/Miyagi/4/93) isolated in Yamagata and
      Sendai Cities, Japan, in 1992/1993. Comparison of total or partial nucleotide
      sequences of the seven RNA segments of C/Yamagata/5/92 with those of 11 previous
      isolates suggested that the 1992 strain is a reassortant which inherited HE, P3,
      NP and M genes from a C/Mississippi/80-like virus and PB2, PB1 and NS genes from
      a C/pig/Beijing/115/81-like virus. Furthermore, it became evident that at least
      two (C/England/83 and C/Yamagata/9/88) of the 11 reference strains are also
      reassortants.

PMID- 8757993
TI  - Intracellular distribution of the ORF4 gene product of varicella-zoster virus is
      influenced by the IE62 protein.
AB  - Varicella-zoster virus (VZV) open reading frame 4-encoded protein (IE4) possesses
      transactivating properties for VZV genes as well as for genes of heterologous
      viruses. The major regulatory immediate-early protein of VZV (IE62) is a
      transactivator of VZV gene expression. In transfection assays, IE4 has been shown
      to enhance activation induced by IE62. To investigate the functional interactions
      underlying this observation, indirect immunofluorescence studies were undertaken
      to determine whether IE62 could influence IE4 intracellular localization in
      transfected cells. In single transfections, IE4 was predominantly found in
      cytoplasm. In cotransfection with IE62, the IE4 localization pattern was altered,
      with nuclear staining predominating over cytoplasmic staining. This effect was
      specific to the IE62 protein since the gene products of ORF63 and ORF61, which
      are also regulatory proteins, did not influence IE4 distribution. The use of IE62
      mutants indicated that IE62 influence is independent of its transactivation
      function and that the integrity of regions 3 and 4 is required. IE62 remained
      nuclear whether IE4 was present or not. These observations underline differences
      in the regulation of gene expression between VZV proteins and their herpes
      simplex virus type 1 homologues. In infected cells, IE4 was only sometimes found
      to colocalize with IE62 in nuclei. This observation suggests that when all VZV
      proteins are present, complex interactions probably occur which could diminish
      the influence of IE62.

PMID- 8757992
TI  - Heterogeneity in the haemagglutinin gene and emergence of the highly pathogenic
      phenotype among recent H5N2 avian influenza viruses from Mexico.
AB  - Molecular changes in the haemagglutinin (HA)-coding regions and proteolytic
      cleavage sites from multiple H5N2 subtype viruses isolated during a recent
      outbreak of avian influenza (AI) in central Mexico have been characterized.
      Eighteen isolates, collected during a 15 month period (October 1993 to January
      1995) from six central states, were sequenced. None of the 18 predicted HA1 amino
      acid sequences were identical and changes were not restricted to a specific
      region of the sequence. Phylogenetic analyses of the HA1 sequences demonstrated
      two virus lineages, designated Puebla and Jalisco, with sequence variation as
      high as 10.5 percent for amino acid and 6.2 percent for nucleotide sequences.
      During the latter months of the surveillance period, highly pathogenic (HP)
      strains of AI emerged causing lethal disease in commercial poultry flocks. In
      each of the HP strains isolated, the HA protein was cleaved in chicken embryo
      fibroblast cells in the absence of trypsin, and two alterations not found in
      earlier non-HP isolates were detected. In the HA protein, HP strains all had a
      glutamic acid --> lysine substitution at amino acid position 324 and an insertion
      of arginine and lysine as new residues 325 and 326. The insertion appears to be
      due to a duplication of the nucleotide sequence AAAGAA at nucleotide positions
      965-970 of the HA1-coding region. Computer-assisted secondary structure analyses
      place the target for the insertion in a predicted RNA stem-loop structure. A
      mechanism is suggested by which the polymerase duplicates the sequence.

PMID- 8757994
TI  - Glycoprotein H (gII/gp108) and glycoprotein L form a functional complex which
      plays a role in penetration, but not in attachment, of bovine herpesvirus 1.
AB  - The glycoproteins of bovine herpesvirus 1 (BHV-1) play important roles in the
      interactions between virions and target cells. A 108 kDa glycoprotein, designated
      gII or gp 108, has been identified by two different panels of monoclonal
      antibodies. The gII- and gp 108-specific monoclonal antibodies were shown to
      react with the same protein, which was identified by N-terminal sequencing as the
      homologue of herpes simplex virus type 1 (HSV-1) gH. When BHV-1 gH was purified
      by immunoadsorbent chromatography, gL was co-purified. The gH-gL complex induced
      the production of antibodies that neutralized virus infectivity and inhibited
      virus penetration. Affinity-purified gH-gL did prevent penetration, but not
      attachment of BHV-1, which suggests that the gH-gL complex is essential for
      penetration of BHV-1 into susceptible cells.

PMID- 8757995
TI  - Effect on substrate binding of an alteration at the conserved aspartic acid-162
      in herpes simplex virus type 1 thymidine kinase.
AB  - Despite the extensive use of antiviral drugs for the treatment of herpesvirus
      infections and as pro-drugs for ablative gene therapy of cancer, little
      structural information about the drug activating enzyme, herpes simplex virus
      type 1 thymidine kinase (TK), was available until recently. In the absence of the
      three-dimensional structure we sought to elucidate the function of the key
      aspartic acid residue (Dl62) present within a highly conserved tri-peptide motif
      that is thought to function in nucleoside binding. In this study we generated a
      mutant, D162Q, by site-directed mutagenesis, purified both the wild-type and
      mutant TKs to near homogeneity by single-step affinity chromatography and
      determined the kinetic parameters for thymidine, ATP, dTMP and dTTP interactions.
      A 12-fold increase in Km for thymidine by D162Q TK (Km = 6.67 microM) relative to
      wild-type enzyme (Km = 0.56 microM) was observed and the absence of any
      alteration in Km for ATP suggests that D162 participates in nucleoside binding.
      Furthermore, the Ki for dTMP is significantly higher for D162Q TK than for HSV-1
      TK which is indicative of a shared or overlapping binding site with thymidine.
      This assessment is further supported by the different inhibition patterns of
      D162Q and wild-type TKs observed using [alpha-32P]5-N3dUMP photoaffinity
      labelling in the presence of thymidine, ganciclovir or dTMP. Interestingly, the
      Ki for dTTP was 30-fold lower for D162Q TK (Ki = 2.2 microM) than for the wild
      type enzyme (Ki = 65.8 microM) which provides further evidence of the importance
      of D162 in TK function.

PMID- 8757996
TI  - Repression by RAZ of Epstein-Barr virus bZIP transcription factor EB1 is
      dimerization independent.
AB  - The hallmark of Epstein-Barr virus (EBV) infection is the establishment of a
      viral genome transcription pattern called latency. The EBV BZLF1 gene product EB1
      (also known as ZEBRA or Zta) is a transcription factor which is essential for the
      switch from latency to the lytic cycle. It has been proposed that latency is
      maintained (i) by the inhibition of EB1 translation via antisense hybridization
      of EBNA1 and EB1 hnRNAs, or (ii) by the inactivation of the EB1 activating
      function via the direct interaction of EB1 with RelA, the retinoic acid receptor
      and p53, or via the titration of EB1 in RAZ:EB1 inactive heterodimers that are
      unable to bind to DNA. RAZ, a fusion protein which contains the EB1 C-terminal
      dimerization and DNA-binding domains fused to the N-terminal 86 amino acids of
      the EBV BRLF1 gene product R, has been described as a trans-dominant negative
      regulator of EB1-activated transcription. We demonstrate here that although RAZ
      efficiently represses EB1-mediated transcriptional activation, the amount of RAZ
      protein expressed is incompatible with repression through the titration of EB1 in
      inactive EB1:RAZ heterodimers. Furthermore, we also demonstrate that RAZ
      efficiently represses transcription activated by an EB1 mutant carrying the GCN4
      homodimerization domain (EB1 gcn4), despite the inability of RAZ and EB1 gcn4 to
      form stable heterodimers.

PMID- 8757997
TI  - Glycoprotein H of human cytomegalovirus is a major antigen for the neutralizing
      humoral immune response.
AB  - A recombinant baculovirus expressing glycoprotein H (gpUL75) of human
      cytomegalovirus was used to examine the humoral immune response in naturally
      infected individuals. Recombinant baculovirus infected insect cells produced two
      forms of gH with molecular masses of 78-82 kDa and 94 kDa. The 94 kDa polypeptide
      was modified by high mannose oligosaccharide side-chains as shown by reduction in
      molecular mass after treatment with endoglycosidases H and F. The 78-82 kDa
      protein represented the non-glycosylated precursor which was resistant to the
      enzymes. In contrast to gH expressed in mammalian cells, the recombinant
      baculovirus expressed gH was transported to the cell surface. Glycoprotein H
      produced in insect cells was reactive with human convalescent sera and all tested
      neutralizing monoclonal antibodies recognizing either linear or conformational
      epitopes. Antibodies reacting with insect cell derived gH were detected in 96
      percent of HCMV seropositive human sera. Using insect cells infected with the gH
      expressing recombinant baculovirus as immunoabsorbent, between 0 percent and 58
      percent of the total virus neutralizing activity was removed from sera of
      individuals with a past HCMV infection. gH must therefore be considered a major
      antigen for the induction of neutralizing antibodies during natural infection.

PMID- 8757998
TI  - Processing of human cytomegalovirus glycoprotein B in recombinant adenovirus
      infected cells.
AB  - Intracellular processing of human cytomegalovirus (HCMV) glycoprotein B (gB;
      gpUL55) expressed by a recombinant adenovirus (Ad-gB) was studied in human A549
      cells as processing events could affect immunogenicity when such viruses are used
      as live-recombinant vaccines. Cleavage of [35S]methionine-labelled gp13O into
      gp93 and gp55 reached a maximum after a 3 h chase. Cleavage was completely
      inhibited by brefeldin A, suggesting that processing normally occurs as a late
      Golgi or post-Golgi event. Uncleaved gp 130 remained completely sensitive to endo
      beta-N-acetylglucosaminidase H (Endo-H) in untreated cells following long chase
      periods, indicating high-mannose oligosaccharides at all of the 18 N-linked
      glycosylation sites (Asn-X-Ser/Thr) and retention in the endoplasmic reticulum.
      Endo-H analysis of gp55 from swainsonine-treated and untreated cells was
      consistent with glycosylation at all three potential sites, with two
      oligosaccharides remaining sensitive to Endo-H and one being processed to Endo-H
      resistance. The heavily glycosylated N-terminal gp93 subunit was not detected by
      [35S]methionine-labelling but was easily detected along with gp55 after labelling
      with [3H]mannose. No cleavage of gp 130 was observed in analogous pulse-chase
      radiolabelling of Ad-gB-infected human fibroblasts, even though these cells are
      permissive for HCMV replication and can process the native gB molecule.
      Processing of gB in recombinant adenovirus-infected A549 cells was generally
      similar to that previously reported for native gB in HCMV-infected fibroblasts.

PMID- 8757999
TI  - Cloning and sequence analysis of the genes encoding DNA polymerase, glycoprotein
      B, ICP18.5 and major DNA-binding protein of rat cytomegalovirus.
AB  - In all herpesviruses a block of genes is present which is composed of the genes
      encoding DNA polymerase, glycoprotein B (gB), ICP18.5 and major DNA-binding
      protein (MDBP). Here we report the cloning and sequencing of this gene block from
      rat cytomegalovirus (RCMV). The gene block spans 13.3 kbp and contains the four
      genes in the order pol, gB, ICP18.5 and MDBP. A similar order of genes has
      previously been reported for human and murine cytomegaloviruses. The pol, gB,
      ICP18.5 and MDBP genes contain open reading frames which have the capacity to
      encode proteins of 1120, 914, 893 and 1281 amino acids, respectively. Comparison
      of the predicted amino acid sequences of the four RCMV proteins with the
      corresponding proteins of other herpesviruses revealed a close relationship
      between RCMV and other cytomegaloviruses, which corroborates the usefulness of
      the RCMV-rat model for studying cytomegalovirus biology.

PMID- 8758000
TI  - Location, DNA sequence and transcriptional analysis of the DNA polymerase gene of
      orf virus.
AB  - Degenerate oligonucleotides representing conserved regions of various DNA
      polymerases hybridized to a region located 26 kb from the left end of the orf
      virus (OV) strain NZ-2 genome. DNA sequence analysis of this region revealed a
      3024 bp open reading frame able to encode a protein with 56 percent amino acid
      identity to the DNA polymerase of vaccinia virus (VAC) and with significant
      homology to other DNA polymerases. Early transcripts derived from the open
      reading frame were detected in RNA purified from OV-infected cells, and 5' ends
      were mapped to a region 8-19 nt downstream from an A/T-rich sequence that
      resembles VAC early promoters. Unlike the VAC gene, the OV DNA polymerase makes
      almost exclusive use of G/C coding options. Attempts to substitute the activity
      of the OV DNA polymerase for its VAC counterpart were unsuccessful. This may
      indicate that the OV DNA polymerase is incompatible with VAC accessory proteins.

PMID- 8758001
TI  - Construction of recombinant myxoma viruses expressing foreign genes from
      different intergenic sites without associated attenuation.
AB  - Two myxoma virus transient dominant selection vectors were constructed and used
      to generate recombinant viruses expressing single and double foreign gene
      insertions from intergenic sites. The intergenic insertion sites were located
      between the myxoma virus genes MJ2 (thymidine kinase) and MJ2a, and MA24 (beta
      subunit RNA polymerase) and MA27 (fusion protein) located approximately 60 and
      113 kb from the left-end of the viral genome, respectively. Recombinant myxoma
      viruses expressing the lacZ gene from either intergenic insertion site retained
      wild-type virulence. However, expression of the gus gene reduced the virulence of
      the recombinant viruses in vivo. Northern blot analysis indicated that the major
      late mRNAs encoding the viral RNA polymerase subunit and fusion protein are both
      of discrete size. Insertion of a foreign gene under the control of a synthetic
      late promoter between the MA24 and MA27 genes results in a specific-sized major
      late transcript for the inserted foreign gene. The MA27 gene transcripts directed
      by these recombinant viruses are heterogeneous in size, implying the typical
      pattern of poxvirus late transcription by random 3'-termination prior to
      polyadenylation. The transcription studies suggest signals located downstream of
      the insertion site direct 3'-processing of late transcripts irrespective of the
      gene immediately upstream.

PMID- 8758002
TI  - Vaccination of cattle with bovine papillomavirus type 4 L2 elicits the production
      of virus-neutralizing antibodies.
AB  - Prophylactic vaccination of cattle with the N terminus (L2a, aa 11-200) of the
      minor capsid protein L2 completely prevented bovine papillomavirus type 4 (BPV-4)
      infection of the alimentary canal. To investigate the mechanisms underlying
      protection from viral infection, sera from vaccinated animals were analysed in
      neutralization assays both in the nude mouse xenograft system and in cattle. BPV
      4 retained its infectivity when incubated with preimmune cattle sera, whereas,
      when incubated with immune sera from animals vaccinated with either whole L2 or
      its N terminus L2a, its infectivity was greatly reduced, indicating that the
      immune sera had neutralizing activity against the virus. This activity could be
      abrogated by absorbing the immune sera with L2 or L2a, thus indicating that virus
      neutralization was due to the presence in the immune sera of anti-L2 antibodies.

PMID- 8758003
TI  - Proliferative T cell responses to the human papillomavirus type 16 E7 protein in
      women with cervical dysplasia and cervical carcinoma and in healthy individuals.
AB  - The levels of proliferative T cell responses to peptides representing the human
      papillomavirus type 16 (HPV-16) E7 protein have been measured using short-term T
      cell lines derived from peripheral blood of healthy women and those with cervical
      dysplasias and carcinoma of the cervix. In healthy individuals 47 percent (7/15)
      responded predominantly to the N- and C-terminal regions of the protein and 6/7
      responders were to a single peptide between amino acids 80-94. In comparison 29
      percent (9/31) of women with cervical dysplasia responded to HPV-16 E7, with a
      significantly reduced response to both the N- and C-terminal regions (P = 0.03
      and 0.038, respectively). A higher proportion of responders was found in patients
      with high grade lesions (56 percent, 5/9) versus those with atypical or low grade
      histology (20 percent, 4/20) and the response to a single peptide between amino
      acids 75-94 was also increased in this patient group (P = 0.044). This may be a
      reflection of higher levels of current or previous exposure to HPV-16 in patients
      with high grade lesions. Correlation of T cell responses with HPV DNA type
      (detected by PCR of cervical biopsy tissue) showed that 3/9 (33 percent) HPV-16
      DNA-positive individuals responded. This suggests that E7 may not be the dominant
      target of the immune response or that the response to E7 is down-regulated in
      these patients. In addition 4/18 (22 percent) HPV-16 DNA-negative individuals
      responded, suggesting that their T cells may have been primed by previous
      exposure to HPV-16 or that a cross-reactive response was detected. Proliferative
      T cell responses to both HPV-16 E7 and L1 were reduced in women with cervical
      carcinoma in comparison to those with cervical dysplasia and healthy controls.
      The observed down-regulation of responses to HPV-16 E7 in women with cervical
      dysplasia and cervical carcinoma may reflect an altered functional balance
      between subsets of T helper cells in HPV-16 infections.

PMID- 8758004
TI  - Scrapie infection can be established readily through skin scarification in
      immunocompetent but not immunodeficient mice.
AB  - Scarification of the skin is a possible route of entry for scrapie infectivity in
      sheep, and for Creutzfeldt-Jakob disease agent in humans within the context of
      occupational exposure to infected brain in the autopsy room or laboratory. The
      effectiveness of skin scarification routes as portals of entry for infectivity
      had not previously been tested experimentally but this study has shown that these
      are efficient routes for establishing infection in mice using the 139A and ME7
      strains of scrapie agent. Scarification had much the same efficiency as
      inoculation by the intraperitoneal, intravenous or perivenous routes but was not
      effective in immunocompromised (SCID) mice. It was concluded that replication of
      infectivity within the lymphoreticular system, which is precluded in SCID mice,
      is a necessary prerequisite for the development of infection in the central
      nervous system following inoculation via scarification.

PMID- 8758005
TI  - Strain specific and common pathogenic events in murine models of scrapie and
      bovine spongiform encephalopathy.
AB  - The development of transmissible spongiform encephalopathies in experimental
      models depends on two major factors: the intracerebral accumulation of an
      abnormal, protease-resistant isoform of PrP (PrPres), which is a host protein
      mainly expressed in neurons; and the existence of different strains of agent. In
      order to make a distinction between pathogenic mechanisms depending upon the
      accumulation of host-derived PrPres and the strain-specific effects, we
      quantified and compared the sequence of molecular [PrPres and glial fibrillary
      acidic protein (GFAP) accumulation] and pathological events in the brains of
      syngeneic mice throughout the course of infection with two different strains of
      agent. The bovine spongiform encephalopathy (BSE) agent exhibits properties
      different from any known scrapie source and has been studied in comparison with a
      classical scrapie strain. Convergent kinetic data in both models confirmed the
      cause-effect relationship between PrPres and pathological changes and showed that
      PrPres accumulation is directly responsible for astrocyte activation in vivo.
      Moreover, we observed a threshold level of PrPres for this effect on astroglial
      cells. However, despite similar infectivity titres, the BSE model produced less
      PrPres than scrapie, and the relative importance of gliosis was higher. The
      comparison of the molecular and pathological features after intracerebral or
      intraperitoneal inoculation also revealed differences between the models.
      Therefore, the mechanisms leading to the targeting and the fine regulation of the
      molecular events seem to be independent of the host PrP and to depend upon the
      agent. The possible involvement of a regulatory molecule accounting for these
      specificities has to be considered.

PMID- 8758006
TI  - Research training and Calman reforms: a role for the MSc?

PMID- 8758007
TI  - Asymptomatic primary hyperparathyroidism.
AB  - The prevalence of hypercalcaemia in the adult population is probably between 0.6
      and 1.1%, sufferers being predominantly women over 50 years of age. Most
      apparently asymptomatic hypercalcaemic patients are found to have primary
      hyperparathyroidism, and may in fact show some symptoms of the condition (lowered
      bone mineral density, cardiovascular disease and/or neuropsychiatric symptoms).
      The criteria for surgical intervention in these cases are discussed in the light
      of the high success rate of parathyroidectomy in experienced hands and the lack
      of effective alternative treatments.

PMID- 8758008
TI  - Chronic pancreatitis: diagnosis and treatment.
AB  - Three-dimensional magnetic resonance cholangiopancreatography is currently the
      most exciting new imaging technique for chronic pancreatitis. Endoscopy-assisted
      duodenal intubation during the secretin-cholecystokinin test reduces intubation
      time in difficult cases. The NBT-para-amino benzoic acid test has been refined to
      enhance its discriminant power. The cholesteryl-[C13]octanoate breath test and
      the faecal elastase test are newer highly sensitive and specific tubeless tests.
      Pain in chronic pancreatitis continues to be a vexing therapeutic issue. Enzyme
      treatment continues despite criticism. Neurotensin is the new suspected mediator
      of the feedback mechanism, which is downregulated by enzyme therapy. Steroid
      ganglion block is an exciting therapeutic tool for pain relief. Endoscopic
      pancreatic sphincterotomy, Dormia basketing and pancreatic stenting in
      conjunction with extracorporeal shock wave lithotripsy should be performed early
      in chronic pancreatitis to prevent parenchymal atrophy with ensuing exocrine and
      endocrine pancreatic dysfunction. The modified Puestow's procedure preserves
      endocrine and exocrine pancreatic functions besides relieving pain. Closed loop
      insulin infusion allows superior management of pancreatic diabetes following near
      total pancreatectomy. The standardised incidence rate of pancreatic cancer is
      16.5 in patients with alcoholic chronic pancreatitis and 100 for tropical chronic
      pancreatitis. Aggressive treatment protocols combining neo-adjuvant
      chemoradiation and intra-operative radiation with surgery are being used to
      improve the prognosis in this dismal complication of chronic pancreatitis.

PMID- 8758009
TI  - Document of care for older people with diabetes. Special Interest Group in
      Diabetes, British Geriatrics Society.

PMID- 8758010
TI  - Influenza vaccination in the elderly.
AB  - There is overwhelming evidence for the clinical efficacy of the influenza
      vaccine, especially in the elderly with chronic disease, reducing mortality and
      hospital admissions. There is also evidence to suggest that the influenza vaccine
      may be beneficial in the healthy elderly. There is some evidence to suggest that
      the antibody response in the elderly to the vaccine may decrease with increasing
      age, although there are several confounding factors that have not been taken into
      account in many of these studies. That aside, even if antibody response is not as
      good as that in younger people, the evidence that vaccination saves lives and
      reduces morbidity in the elderly means that the vaccination should be offered to
      elderly patients at high risk and perhaps even to the elderly healthy population.
      Although vaccination of an elderly at-risk patient does not necessarily mean that
      that particular patient will mount an appropriate antibody response, a
      significant number of elderly patients will respond appropriately. Serious side
      effects from vaccination are extremely rare and the more common side-effects are
      mild and self-limiting. Increasing the number of elderly people receiving the
      influenza vaccination will not only result in cost savings for the National
      Health Service in terms of reduced hospitalisation but, more significantly, the
      elderly will benefit in terms of reduced morbidity and mortality.

PMID- 8758011
TI  - Training in anaesthesia: the US perspective.
AB  - In the light of the recent Calman Report and the Royal College of Anaesthetists
      document 'Specialist training in anaesthesia, supervision and assessment', there
      is currently much debate concerning the future of anaesthesia training in the UK.
      We present a description of anaesthesia training in the US for discussion and
      comparison. US residency training is short and seamless. It is highly structured,
      but retains a capacity for specialisation. It may offer ideas for the future
      direction of training in the UK.

PMID- 8758012
TI  - Klippel-Trenaunay syndrome.
AB  - The Klippel-Trenaunay syndrome, typically characterised by the triad of cutaneous
      haemangioma, venous varicosities, and limb hypertrophy, may also have a formes
      frustes presentation, with absence of the cutaneous naevus. A case is reported in
      a 75-year-old woman with a presumptive diagnosis of renovascular hypertension.

PMID- 8758013
TI  - Changes in haemodynamic parameters following Tai Chi Chuan and aerobic exercise
      in patients recovering from acute myocardial infarction.
AB  - In this study, 126 patients (90 males, average age 56 years, range 39-80) were
      randomised to Wu Chian-Ch'uan style Tai Chi (38), aerobic exercise (41) or a non
      exercise support group (47) following acute myocardial infarction. Patients
      attended twice weekly for three weeks then weekly for a further five weeks. Heart
      rate and blood pressure were recorded before and after each session. Over the 11
      sessions of exercise there was a negative trend in diastolic blood pressure only
      in the Tai Chi group (Rs = 0.79, p < 0.01). Significant trends in systolic blood
      pressure occurred in both exercise groups (Rs = 0.64 and 0.63, both p < 0.05).
      Only four (8%) patients completed the support group eight-week programme which
      was less than the number completing Tai Chi (82%; p < 0.001) and aerobic exercise
      groups (73%; p < 0.001).

PMID- 8758014
TI  - Metformin treatment in NIDDM patients with mild renal impairment.
AB  - Metformin is contraindicated in patients with renal failure because of the risk
      of lactic acidosis. This study assessed the complications of metformin treatment
      in patients with non-insulin-dependent diabetes mellitis with normal and raised
      serum creatinine. Subjects using metformin with serum creatinine above the upper
      reference range (120 mu mol/l) were identified (n = 17) from a hospital diabetes
      register; those with abnormal liver function, cardiac failure, peripheral
      vascular disease or recent severe illness were excluded. Reference plasma lactate
      levels were established, mean 1.742 mu mol/l (SD 0.819) using age-matched non
      diabetic subjects. Age-matched patients treated with metformin with normal serum
      creatinine levels formed the control group (n = 24). Details of gastrointestinal
      disturbance were recorded, and plasma lactic acid and vitamin B12 levels
      measured. The median total daily dose of metformin in both groups was 1700 mg.
      The mean plasma lactate in subjects with serum creatinine 80-120 mu mol/l (2.640
      mmol/l (SD 1.434) p < 0.02) was higher than non-diabetic control levels while
      diabetic subjects with serum creatinine 120-160 mumol/l had a mean of 2.272
      mmol/l (SD 0.763) p < 0.05. There was no significant difference between the two
      groups taking metformin, nor any significant difference in the reporting of
      gastrointestinal symptoms between the groups on metformin (11.76% vs 12.5%).
      Plasma lactic acid levels are higher in diabetic subjects taking metformin
      compared with healthy volunteers but, within the diabetic groups, the small
      elevation of serum creatinine was not associated with higher plasma lactate
      levels.

PMID- 8758015
TI  - Deep cerebral venous thrombosis presenting as an encephalitic illness.
AB  - Three cases of deep cerebral vein thrombosis presenting as encephalitic illnesses
      are described. Thyrotoxicosis was present in one case, ulcerative colitis in one
      case and an anticardiolipin antibody was detected in two cases. All three
      patients were on oestrogen and progesterone. Magnetic resonance imaging and
      angiography allowed rapid confirmation of the diagnosis and permitted non
      invasive follow up of this condition. The first two patients made complete
      clinical recoveries despite having thalamic infarction, in one case bilaterally,
      demonstrable radiologically.

PMID- 8758016
TI  - Coronary subclavian steal syndrome following coronary by-pass surgery.
AB  - The coronary steal syndrome is an uncommon but well recognised occurrence
      following coronary artery by-pass surgery using the internal mammary artery. We
      report a case of coronary steal successfully treated with percutaneous
      transluminal angioplasty of a subclavian stenosis.

PMID- 8758017
TI  - Bilateral endogenous Escherichia coli endophthalmitis: a devastating complication
      in an insulin-dependent diabetic.
AB  - We report a case of bilateral endogenous Escherichia coli endophthalmitis in an
      insulin-dependent diabetic. This condition appears to occur almost exclusively in
      diabetics, and is invariably related to a urinary tract infection. Treatment of
      any infection in diabetics should be aggressive, and any deterioration in vision
      should be addressed promptly.

PMID- 8758018
TI  - Elevated serum prostate-specific antigen and pancreatic carcinoma.
AB  - We report a case of elevated serum prostate-specific antigen-like
      immunoreactivity in a man with a disseminated pancreatic carcinoma.

PMID- 8758019
TI  - Insulin resistance and development of diabetes mellitus associated with megestrol
      acetate therapy.
AB  - We describe a case of diabetes mellitus induced by megestrol acetate in a patient
      with the acquired immunodeficiency syndrome. Metabolic studies including an
      arginine infusion test excluded an insulinopenic state and suggested insulin
      resistance as the underlying mechanism for hyperglycaemia. Withdrawal of
      megestrol acetate resulted in rapid correction of all metabolic abnormalities and
      eliminated the need for exogenous insulin therapy.

PMID- 8758020
TI  - Digoxin toxicity presenting as encephalopathy.
AB  - We describe two cases of digoxin toxicity presenting with clinical and
      electroencephalographic evidence of encephalopathy without other features of
      digoxin toxicity.

PMID- 8758021
TI  - Profound anaemia in an elderly man.

PMID- 8758022
TI  - Massive haemobilia.

PMID- 8758023
TI  - Weight loss.

PMID- 8758024
TI  - An unusual but important cause of sciatica.

PMID- 8758025
TI  - Breathlessness in an Afro-Caribbean woman.

PMID- 8758026
TI  - Tingling extremities in a young man.

PMID- 8758027
TI  - Glottic angioedema, ciprofloxacin, and ACE inhibitors.

PMID- 8758028
TI  - Anorexia nervosa.

PMID- 8758029
TI  - Modifiers of non-specific symptoms in occupational and environmental syndromes.
AB  - Many occupational and environmental health hazards present as an increased
      reporting of non-specific symptoms such as headache, backache, eye and
      respiratory irritation, tiredness, memory problems, and poor concentration. The
      pattern and number of such symptoms is surprisingly constant from hazard to
      hazard suggesting that common psychological and social factors, not directly
      related to the exposure may be involved. A recent workshop (see acknowledgements)
      was held to review the pattern of symptoms in varying hazardous situations and
      the psychological mechanisms behind the genesis and maintenance of symptoms. The
      involvement of both direct physicochemical and psychological mechanisms in
      symptom generation and reporting in any situation was discussed and is reported
      here. A model that identifies the issues that need to be considered in any
      epidemiological study based on the incidence or prevalence of non-specific
      symptoms is proposed.

PMID- 8758030
TI  - Shiftwork and mortality from ischaemic heart disease.
AB  - OBJECTIVES: To investigate the relation between shift work and death from
      ischaemic heart disease (IHD). METHODS: A nested case-control approach was used.
      The cohort comprised male manual workers who joined an industrial company aged 50
      years or under between 1 January 1950 and 31 December 1992 and worked there for
      at least one month. Cases were 467 cohort members who died during the same period
      aged 75 years or under, with ischaemic heart disease (IHD) (international
      classification of diseases (ICD) 410-414) coded from the death certificate. For
      each case a control worker was chosen, who joined the company at the same age and
      in the same period but who survived the case. Work status (shift work or day
      work) was assigned to cases for their entire employment and to controls for that
      part of their employment which preceded the matching case's death. The main
      source of information was historical personnel records containing pay codes which
      differed for day work and shift work. Information on weight, height, blood
      pressure, and smoking from a pre-employment medical was available. RESULTS: Two
      thirds of subjects had been employed for at least one month as shift workers and
      there was evidence that they had slightly better health at recruitment than day
      workers. The odds ratio for shift workers during the period starting 10 years
      after shift work began, and after adjustment for height, body mass index, blood
      pressure, smoking, duration of employment, and job status (skilled or unskilled)
      was 0.90 (90% confidence interval (90% CI): 0.68-1.21). There was no relation
      between risk of IHD death, and duration of shift work, but there was evidence of
      a reduced risk when actively employed as a shift worker, together with an
      increased risk in the first five years after leaving shift work to do day work.
      CONCLUSIONS: Shift work did not increase the risk of death from ischaemic heart
      disease in this study. Those workers with poorer cardiovascular health may be
      under represented in groups with longer shift work experience because of health
      related selection out of shift work.

PMID- 8758031
TI  - Shift work, nitrous oxide exposure, and spontaneous abortion among Swedish
      midwives.
AB  - OBJECTIVES: To study the relation between irregular work hours, nitrous oxide
      (N2O) exposure, and the risk of spontaneous abortion. METHODS: All 3985 female
      members of the Swedish Midwives Association in 1989, born in 1940 or later,
      received a questionnaire on exposure before and during all of their pregnancies.
      Questions on work conditions covered occupation, extent of employment, workplace,
      work schedules, use of anaesthetics, and work load. The association between
      exposure variables and spontaneous abortion was analysed by logistic regression
      models. RESULTS: Night work and three shift schedules among midwives showed
      increased odds ratios (ORs) (95% confidence intervals (95% CI)) 1.63 (0.95-2.81)
      and 1.49 (0.86-2.59), respectively. The ORs of late spontaneous abortions (after
      the 12th week of pregnancy) was increased for night work 3.33 (1.13-9.87). Use of
      N2O (> 50% of the deliveries) was not associated with increased risk of
      spontaneous abortion OR 0.95 (0.62-1.47). Frequent or permanent shortage of staff
      was related to an increased risk of spontaneous abortions before the 13th week of
      pregnancy. CONCLUSIONS: The results support the hypothesis that night work and
      high work load increase the risk of spontaneous abortion.

PMID- 8758032
TI  - Effect of subchronic in vivo exposure to nitrogen dioxide on lung tissue
      inflammation, airway microvascular leakage, and in vitro bronchial muscle
      responsiveness in rats.
AB  - OBJECTIVES: In a previous study on bronchoalveolar lavage fluid from rats exposed
      in vivo for seven days to 10 ppm nitrogen dioxide (NO2), it has been shown that
      there is an influx of macrophages into the airways. The present study
      investigated the effect of seven day exposure to 10 ppm NO2, on: (a) lung tissue
      inflammation and morphology; (b) airway microvascular leakage; (c) in vitro
      contractile response of main bronchi. METHODS: Lung tissue was studied by light
      microscopy, after fixing the lungs by inflation with 4% formalin at a pressure of
      20 cm H2O. Microvascular leakage was measured by extravasation of Evans blue dye
      in the larynx, trachea, main bronchi, and intrapulmonary airways. Smooth muscle
      responsiveness was evaluated by concentration-responses curves to acetylcholine
      (10(-9)-10(-3) M), serotonin (10(-9)-10(-4) M), and voltage-response curves (12
      28 V) to electrical field stimulation. RESULTS: Histology showed an increased
      total inflammation at the level of respiratory bronchioles and alveoli. No influx
      of inflammatory cells was found in the main bronchi. A loss of cilia in the
      epithelium of small airways and ectasia of alveolar capillaries was also found.
      By contrast, no alterations to microvascular permeability or modification of
      bronchial smooth muscle responsiveness was found. CONCLUSIONS: Subchronic
      exposure to 10 ppm NO2 causes airway inflammation and structural damage, but does
      not cause any persistent alteration to microvascular permeability or bronchial
      smooth muscle responsiveness in rats.

PMID- 8758033
TI  - Wool and grain dusts stimulate TNF secretion by alveolar macrophages in vitro.
AB  - OBJECTIVE: The aim of the study was to investigate the ability of two organic
      dusts, wool and grain, and their soluble leachates to stimulate secretion of
      tumour necrosis factor (TNF) by rat alveolar macrophages with special reference
      to the role of lipopolysaccharide (LPS). METHODS: Rat alveolar macrophages were
      isolated by bronchoalveolar lavage (BAL) and treated in vitro with whole dust,
      dust leachates, and a standard LPS preparation. TNF production was measured in
      supernatants with the L929 cell line bioassay. RESULTS: Both wool and grain dust
      samples were capable of stimulating TNF release from rat alveolar macrophages in
      a dose-dependent manner. The standard LPS preparation caused a dose-dependent
      secretion of TNF. Leachates prepared from the dusts contained LPS and also caused
      TNF release but leachable LPS could not account for the TNF release and it was
      clear that non-LPS leachable activity was present in the grain dust and that wool
      dust particles themselves were capable of causing release of TNF. The role of LPS
      in wool dust leachates was further investigated by treating peritoneal
      macrophages from two strains of mice, LPS responders (C3H) and LPS non-responders
      (C3H/HEJ), with LPS. The non-responder mouse macrophages produced very low
      concentrations of TNF in response to the wool dust leachates compared with the
      responders. CONCLUSIONS: LPS and other unidentified leachable substances present
      on the surface of grain dust, and to a lesser extent on wool dust, are a trigger
      for TNF release by lung macrophages. Wool dust particles themselves stimulate
      TNF. TNF release from macrophages could contribute to enhancement of inflammatory
      responses and symptoms of bronchitis and breathlessness in workers exposed to
      organic dusts such as wool and grain.

PMID- 8758034
TI  - Cancer mortality among shoe manufacturing workers: an analysis of two cohorts.
AB  - OBJECTIVES: To examine the cancer risk of shoe manufacturing workers and evaluate
      whether the risk was associated with exposure to leather dust and solvents.
      METHODS: Data from two historical cohort studies of shoe workers were expanded
      and analysed in parallel. A total of 4215 shoemakers from England contributing
      103 726 person-years at risk and 2008 shoemakers from Florence, Italy,
      contributing 54,395 person-years at risk were included in the analysis. Exposure
      to leather dusts and solvents from glues was evaluated on the basis of job title
      information. Standardised mortality ratios (SMR) were calculated as ratios of
      observed deaths (Obs) over expected derived from national mortalities. RESULTS:
      Overall mortality was lower than expected in both cohorts (English cohort: Obs
      3314, SMR 81, 95% confidence interval (95% CI) 78-84; Florence cohort: Obs 333,
      SMR 87, 95% CI 78-97). An increased risk of nasal cancer was found (English
      cohort: Obs 12, SMR 741; Florence cohort: Obs 1, SMR 909). 10 of the 13 cases
      occurred among English workers employed in the manufacture of welted boots (SMR
      926, 95% CI 444-1703), a sector of the industry thought to have had the highest
      exposure to leather dust. Mortality from leukaemia was not increased in the
      English cohort (Obs 16, SMR 89), but was increased in the Florence cohort (Obs 8,
      SMR 214, 95% CI 92-421); and the highest risk was found among shoe workers in
      Florence who were first exposed between 1950 and 1959 when exposure to benzene
      was substantial (Obs 3, SMR 536, 95% CI 111-1566). Some evidence for an excess
      risk of stomach, bladder, and kidney cancer, as well as multiple myeloma and non
      Hodgkin's lymphoma was also found in the Florence cohort only among workers
      employed in jobs with the highest exposure to solvents. CONCLUSIONS: These
      findings confirm the associations between exposure to leather dust and nasal
      cancer and between exposure to benzene and leukaemia in the shoe manufacturing
      industry and suggest that the risk of other cancers may be increased among
      workers exposed to solvents or glues.

PMID- 8758035
TI  - Lung cancer in asbestos cement workers in Denmark.
AB  - OBJECTIVES: To study the relative and absolute risks of main types of lung cancer
      in a cohort of asbestos cement workers from Denmark. METHOD: A cohort of 7887 men
      and 576 women employed between 1928 and 1984 was compiled from the personnel
      files of Danish Eternit Production. The cohort was followed up for deaths,
      emigrations, and incident cancer cases during the period 1943-90. The observed
      number of lung cancer cases in the cohort was compared with the expected number
      based on incidences for the Danish population. Internal comparison was made with
      Poisson modelling. RESULTS: A total of 226 lung cancer cases were observed (223
      men and three women). The standardised incidence ratio (SIR) for all lung cancer
      among men was 1.7 (observed number 223, expected number 129.7, 95% confidence
      interval (95% CI) 1.5-2.0). The SIRs were raised for all main types of lung
      cancer; adenocarcinoma 2.6, squamous cell carcinoma 1.7, and anaplastic carcinoma
      1.5. The higher SIR for adenocarcinomas was found particularly with a latency
      period of 25 years or more. Among the 93 excess lung cancer cases, 36 were
      squamous cell carcinomas and 32 were adenocarcinomas. CONCLUSION: Asbestos cement
      work is associated with an increased risk of lung cancer of all main types.
      During the first 25 years after the start of employment this excess risk is
      shared almost equally between the different histological types of lung cancer,
      but the risk of adenocarcinomas is clearly higher after this point.

PMID- 8758036
TI  - Occupational exposure to poultry and prevalence of antibodies against Marek's
      disease virus and avian leukosis retroviruses.
AB  - OBJECTIVES: To compare the prevalence of antibodies against Marek's disease
      herpes virus (MDV) and against avian leukosis viruses type C (ALV) in groups of
      workers exposed to poultry and in unexposed groups. METHODS: Antibodies directed
      against avian viral proteins were detected by enzyme linked immunosorbent assay
      in 549 subjects. Exposure to chickens was high in two subgroups: farmers on
      intensive chicken farms and workers at chicken slaughterhouses. One subgroup,
      traditional farmers on dairy or pig farms with poultry, had moderate exposure to
      poultry. Another subgroup, farmers and slaughterhouse workers on quail farms, had
      high exposure to quails. Three subgroups were not exposed to chickens: farmers on
      dairy or pig farms without poultry, workers at cattle slaughterhouses, and white
      collar workers. Also, MDV antibodies were tested after serum sample adsorption
      with chicken antigens in 134 serum samples. RESULTS: The prevalence of antibodies
      against MDV was significantly higher in the exposed subgroups than in unexposed
      groups (odds ratio (OR) 6.17; 95% confidence interval (95% CI) 3.91-9.75). No
      association was found between seroprevalence and age. However, higher prevalence
      was found among women and was related to duration of exposure to chickens. The
      concentration of antibodies from a few subjects remained very high after
      adsorption. Significant differences between the men and women were found for the
      prevalence of antibodies for ALV but were not related to exposure to chickens.
      CONCLUSIONS: The prevalence of antibodies against MDV was significantly higher
      among workers exposed to chickens and was related to sex and duration of
      exposure. The higher prevalence of antibodies against avian oncogenic viruses
      found among women compared with men may be induced by differences in exposure or
      by genetic factors. The meaning of these high titres could be related to the
      presence of MDV in humans. Because the involvement of animal oncogenic viruses in
      human cancer is indicated by epidemiological and some experimental studies, the
      integration of viral DNA in human cells needs to be investigated.

PMID- 8758037
TI  - Semen quality of men employed at a lead smelter.
AB  - OBJECTIVE: To evaluate the effects of recent and long term occupational lead
      exposure on indicators of male reproductive health. METHODS: In a cross sectional
      study of male employees of a lead smelter (n = 2469), blood samples were obtained
      from 152 workers including 119 who also provided semen samples. Semen analysis
      and serum concentrations of testosterone, follicle stimulating hormone, and
      luteinising hormone were used as indicators of reproductive health. Semen and
      hormone variables were examined in relation to measures of current and long term
      body lead burden estimated from current blood lead concentrations and historical
      blood lead monitoring data. RESULTS: For current blood lead concentration groups
      of < 15, 15-24, 25-39, > 40 micrograms/dl, the geometric mean sperm
      concentrations were, respectively, 79.1, 56.5, 62.7, and 44.4 million cells/ml
      and geometric mean total sperm counts were 186, 153, 137, and 89 million cells (P
      for trend 0.04). Compared with workers with blood lead concentrations less than
      15 micrograms/dl, workers with current blood lead concentrations of 40
      micrograms/dl or more had an increased risk of below normal sperm concentration
      (odds ratio (OR) 8.2, 95% confidence interval (95% CI) 1.2-57.9) and total sperm
      count (OR 2.6, 95% CI 0.4-15.7), based on World Health Organisation standards.
      Independent of current lead exposure, sperm concentration, total sperm count, and
      total motile sperm count were inversely related to measures of long term lead
      exposure. No association was found between lead exposure and measures of sperm
      motility, sperm morphology, or serum concentrations of reproductive hormones.
      CONCLUSIONS: Blood lead concentrations below the currently accepted worker
      protection criteria seem to adversely affect spermatogenesis.

PMID- 8758038
TI  - Biological indicators of exposure to total and respirable aluminium dust
      fractions in a primary aluminium smelter.
AB  - OBJECTIVES: The study attempts to define biological indicators of aluminium
      uptake and excretion in workers exposed to airborne aluminium compounds in a
      primary aluminium smelter. Also, this study defines the total and respirable
      aluminium dust fractions in two different potrooms, and correlates their
      concentrations with biological indicators in this group of workers. METHODS: Air
      was sampled at defined work sites. Non-destructive and conventional techniques
      were used to find total and respirable aluminium content of the dust. Blood and
      urine was collected from 84 volunteers employed at various work stations
      throughout the smelter and from two different cohorts of controls matched for
      sex, age, and socioeconomic status. Aluminium in serum samples and urine
      specimens was measured by flameless atomic absorption with a PE 4100 ZL
      spectrometer. RESULTS: The correlation of aluminium concentrations in serum and
      urine samples with the degree of exposure was assessed for three arbitrary
      exposure categories; low (0.036 mg Al/m3), medium (0.35 mg Al/m3) and high (1.47
      mg Al/m3) as found in different areas of the smelter. At medium and high
      exposure, the ratio of respirable to total aluminium in the dust samples varied
      significantly. At high exposure, serum aluminium, although significantly raised,
      was still within the normal range of an unexposed population. The workers with
      low exposure excreted aluminium in urine at levels significantly higher than the
      controls, but still within the normal range of the population. However, potroom
      workers with medium and high exposure had significantly higher urinary aluminium
      than the normal range. CONCLUSIONS: It is concluded that only urinary aluminium
      constitutes a practical index of occupational exposure at or above 0.35 mg Al/m3,
      and that the respirable fraction of the dust may play a major role in the
      biological response to exposure to aluminium in a smelter environment.

PMID- 8758039
TI  - A cross sectional study of chemical industry workers with occupational exposure
      to persulphates.
AB  - OBJECTIVES: Hair bleaches containing persulphates have been identified as the
      cause of occupational asthma in hairdressers. Also employees in persulphate
      production with occupational asthma have been described. It was the aim of this
      study to give an estimate of the prevalence of asthma due to persulphates in
      chemical workers with exposure to ammonium and sodium persulphate. METHODS: A
      cross sectional study was performed in 32 of 33 employees of a persulphate
      producing chemical plant. Eighteen of 23 workmen from the same plant with no
      exposure to persulphates were taken as controls. Also, information was collected
      from medical records of the seven subjects who had left the persulphate
      production for medical reasons since 1971. Data were recalled by a questionnaire,
      skin prick tests were performed with five environmental allergens, and ammonium
      and sodium persulphate (80 mg/ml). Specific immunoglobulin E (IgE) to the same
      environmental allergens as in the skin test, and total IgE were measured. Lung
      function and bronchial responsiveness to histamine were assessed by standard
      procedures. Workplace concentrations of ammonium and sodium persulphate were
      estimated by area and personal monitoring. The amount of persulphate was analysed
      as sulphur by inductively coupled plasma emission spectrometry. RESULTS: Work
      related rhinitis was reported by one subject with exposure to persulphates,
      conjunctivitis and bronchitis were reportedly related to work by two controls.
      There were no cutaneous reactions to persulphates in either group. Four non
      atopic subjects exposed to persulphates, and two controls, one atopic and one non
      atopic, were considered to be hyperresponsive to histamine. Three subjects
      exposed to persulphates with bronchial hyperresponsiveness (provocation dose of
      histamine causing a 15% fall in forced expiratory volume in one second (PD15
      FEV1) < or = 1 mg) did not show variability in peak expiratory flow of > or =
      20%, the rest refused peak flow measurements. None of the variables showed
      significant differences between the groups (P > 0.05). Six of the exworkers left
      because of work related contact dermatitis. Mean values for workplace
      concentrations of ammonium and sodium persulphate within the bagging plant were
      below 1 mg/m3, and the maximal concentrations were 1.4 mg/m3 and 3.6 mg/m3,
      respectively. CONCLUSION: Exposure to workplace concentrations of ammonium and
      sodium persulphate of about 1 mg/m3 in this chemical plant was not associated
      with a risk of occupational asthma.

PMID- 8758040
TI  - Prevalence of dermatoses and skin sensitisation associated with use of pesticides
      in fruit farmers of southern Taiwan.
AB  - OBJECTIVES: Agricultural workers are known to have occupational skin diseases.
      The prevalence and pattern of skin diseases are unknown in Taiwanese fruit
      farmers. The objective of this study is to determine the work exposure,
      prevalence of skin diseases, and sensitivity to common skin allergens and
      agricultural chemicals in fruit farmers of southern Taiwan. METHODS: 122 fruit
      farmers who regularly prepared and sprayed pesticides and a group of 63 printing
      press workers with no known exposure to pesticides were examined and patch tested
      with common skin allergens and agricultural chemicals. The farmers were also
      interviewed for their work habits, use of protective clothing, and exposure to
      pesticides. RESULTS: Most farmers reported regular use of hat, boots, and mask,
      but not gloves, raincoat, and goggles. This resulted in frequent skin contact
      with pesticides especially on the hands and face. About 30% of farmers had hand
      dermatitis, and more than two thirds had pigmentation and thickening on the
      hands. Fungal infection of the skin was noted in a quarter of subjects. By patch
      test, farmers and the printing press workers had a similar rate of sensitivity to
      common skin allergens. 40% of farmers were sensitive to agricultural chemical
      allergens, which was about twofold higher than that of the comparison group.
      Farmers were most frequently sensitive to Captofol, Folpet, and Captan which were
      associated with dermatitis on the volar aspects of the hands. CONCLUSIONS: Fruit
      farmers in southern Taiwan had a high prevalence of skin diseases related to use
      of pesticides, and appropriate protective measures and work practices should be
      taken to prevent such problems.

PMID- 8758041
TI  - Acute irreversible renal failure.

PMID- 8758042
TI  - Tourette's syndrome: a disorder of cingulate and orbitofrontal function?
AB  - We discuss the clinical characteristics of tics and Tourette's syndrome (TS) and
      also possible treatment options. Based upon an overview of published
      pathophysiological and PET data, and the results of a recent PET study of changes
      in opioid receptor binding in TS, we hypothesize that the disease arises due to
      dysfunction within the cingulate and orbitofrontal cortex. The beneficial effects
      of dopamine receptor antagonists and dopamine-depleting agents in TS are
      suggested to be mediated via basal ganglia-thalamofrontal circuits, while opioid
      agents may act directly on the cingulate.

PMID- 8758043
TI  - Anti-thrombotic therapy for non-rheumatic atrial fibrillation.
AB  - Recent randomized trials of antithrombotic therapy in non-rheumatic atrial
      fibrillation have helped to clarify the benefits of warfarin and aspirin. Low
      risk patients (normotensives aged < 60 with normal left ventricular function)
      have a small risk of thromboembolic events and are unlikely to benefit
      significantly from anticoagulants, but may benefit from aspirin with little
      increase in risk of bleeding. High-risk patients (> 75 years, impaired left
      ventricular function, previous thromboembolism and/or associated conditions such
      as hypertension and diabetes mellitus) have an increased risk of thromboembolism,
      and benefit from long-term anticoagulant therapy to a greater degree than with
      aspirin, although at a risk of increased bleeding complications.

PMID- 8758044
TI  - Survivors of acute renal failure who do not recover renal function.
AB  - Overall survival in 1095 patients with severe acute renal failure (ARF) between
      1984 and 1995 was 59.5%. Of these, 107 (16.2%) remained dependent on long-term
      dialysis. The frequency of end-stage renal failure (ESRF) in survivors of ARF
      varied between 3% and 41% according to the cause of ARF, being highest in those
      with acute renal parenchymal disease (in whom survival was also among the highest
      at 84%) and lowest in ARF due to obstetrics and trauma. Patients failing to
      regain adequate renal function did not appear to differ on clinical grounds from
      survivors who became dialysis-independent. Survival in those requiring long-term
      dialysis was less good than for other patients with ESRF, partly due to excess
      mortality in those for whom vascular disease or surgery was the precipitating
      cause of ARF. Six patients recovered sufficient renal function to become
      independent of dialysis after 3-18 months on regular dialysis therapy (6-21
      months after onset of ARF). ESRF resulting from ARF is more frequent than
      previously reported. This increase may be due to a changing case-mix, increasing
      age of patients (and hence reduced capacity for renal recovery), and an increase
      in aggressive surgery for patients with advanced vascular disease. This presents
      a significant and increasing problem, with implications for both clinical
      management and the provision of dialysis services.

PMID- 8758045
TI  - Predictors of outcome in Cryptococcus neoformans var. gattii meningitis.
AB  - In Papua New Guinea, Cryptococcus neoformans var. gattii meningitis has a high
      fatality rate even in immunocompetent patients. Our retrospective study attempted
      to identify marker of poor prognosis. Of 88 immunocompetent patients, 30 (34.1%)
      died, usually soon after admission, and mortality was higher in men (p = 0.025)
      and older patients (p = 0.039). Death was associated with altered consciousness
      (p < 0.001), a history of convulsions prior to treatment (p = 0.002) and a
      maximum systolic blood pressure of > 150 mmHg (p = 0.017). These data suggest
      that death results from raised intracranial pressure and subsequent tentorial
      herniation. However, CSF opening pressure measured on admission was raised in
      29/36 (81%) patients and did not predict outcome. In survivors, relapse was
      uncommon and was not predicted by discharge serum cryptococcal antigen titres,
      which were frequently raised on completion of therapy in asymptomatic patients.
      Mortality may be reduced if efforts are made to lower intracranial pressure in
      those patients who present with markers of poor prognosis.

PMID- 8758046
TI  - The clinical spectrum of postpartum thyroid disease.
AB  - The clinical and biochemical features of postpartum thyroid disease were analysed
      in 152 antithyroid peroxidase antibody-positive (anti-TPO+ve) women and compared
      with 239 anti-TPO-ve age-matched control postpartum women. All were assessed
      monthly for up to 12 months postpartum. Seventy three anti-TPO+ve women developed
      postpartum thyroiditis (PPT): 19.2% hyperthyroid alone, 49.3% hypothyroid alone,
      and 31.5% characterized by hyper- followed by hypothyroidism. None of the
      antibody-negative women developed any thyroid dysfunction. A significant increase
      in many of eleven symptoms of hypothyroidism and some of eight symptoms of
      hyperthyroidism compared to control women was observed in all anti-TPO+ve women,
      independent of thyroid status. This was particularly seen in women who later
      developed PPT when they were euthyroid, but was also observed in euthyroid anti
      TPO+ve women who showed no decline of thyroid function during the postpartum
      period. Although PPT is usually transient, this condition, and the euthyroid
      antibody-positive state, may be associated with significant symptomatology,
      including an increased incidence of minor to moderate depression. Early
      recognition of this syndrome by antenatal screening of thyroid antibodies may
      contribute to improved management of women during the postpartum period.

PMID- 8758047
TI  - Genetic analysis of thermolabile methylenetetrahydrofolate reductase as a risk
      factor for myocardial infarction.
AB  - Hyperhomocyst(e)inemia is associated with an increased risk of coronary artery
      disease and myocardial infarction. Both genetic and environmental factors
      influence the plasma level of homocysteine. One of the metabolic pathways for
      homocysteine involves the enzyme methylenetetrahydrofolate reductase (MTHFR),
      which regulates the conversion of homocysteine to methionine. A thermolabile
      variant of MTHFR is associated with reduced enzyme activity and increased plasma
      homocysteine levels. Recently, the cause of this variant of MTFHR has been
      identified as a single base change altering an alanine to a valine residue in the
      protein. Using a PCR-based assay to distinguish the normal and thermolabile
      variants of MTHFR in this study, we investigated whether the thermolabile variant
      is a genetic risk factor for myocardial infarction. In a study of 532 subjects
      (310 myocardial infarction patients and 222 population-based controls), we found
      no difference in either MTHFR genotype distribution (p = 0.57) or allele
      frequencies (p = 0.68) between cases and controls. The allele frequencies of the
      thermolabile variant were 0.34 and 0.35 in cases and controls, respectively. The
      age- and sex-stratified odds ratio for risk of myocardial infarction associated
      with homozygosity for the thermolabile variant was 0.85 (95% CI 0.50-1.50, p =
      0.57) and that with carriage of the thermolabile allele was 1.06 (95% CI 0.73
      1.52, p = 0.76). The odds ratios remained non-significant when restricted to
      young subjects (< 60 years) or males, and were not influenced by several other
      risk factors for myocardial infarction considered either singly or in
      combination. Interestingly, in both cases and controls, there was a trend toward
      a higher prevalence of hypertension in subjects carrying the normal allele,
      although as this is a post-hoc finding it needs to be interpreted with caution.
      The thermolabile variant of MTHFR is not a major risk factor for myocardial
      infarction and is unlikely to explain a significant proportion of the reported
      association of hyperhomocyst(e)inemia with coronary artery disease.

PMID- 8758048
TI  - Fibrodysplasia (myositis) ossificans progressiva: clinicopathological features
      and natural history.
AB  - Patients with fibrodysplasia (myositis) ossificans progressiva (FOP) (n = 28)
      were studied for up to 24 years. All had characteristic short big toes
      potentially recognizable at birth; there were radiographic changes in the toes,
      thumbs, cervical spine and metaphyses of the long bones, including exostoses.
      Ossification in the large skeletal muscles began from birth to 16 years (mean age
      4.6 years) initially in 25 patients in the neck and upper spinal muscles, and
      later around the hips, major joints and jaw. The rate and extent of disability
      was unrelated to the time of onset. There was no evidence that any form of
      treatment produced consistent benefit. Despite the unique combination of skeletal
      abnormalities and ectopic ossification, the first diagnosis in patients with FOP
      was often wrong and usually delayed after ectopic ossification began (mean 2.7
      years, range 0-14). Except where presentation was unusual, such as progressive
      stiffness, this delay was mainly due to failure to recognize the significance of
      the abnormal toes. The most frequent erroneous histological diagnoses were soft
      tissue sarcoma or fibromatosis. This series emphasizes the usually incorrect
      initial diagnosis, the misinterpretation of the histology, the unpredictable
      prognosis and the failure of current treatment. Despite its extreme rarity, there
      is a need for wider knowledge of this condition both to avoid clinical errors and
      to stimulate research.

PMID- 8758049
TI  - Methods of estimating cardiac output in the field.
AB  - Simultaneous estimation of cardiac output (CO) by thoracic electrical
      bioimpedance (TEB) and thermodilution (TD) confirmed the results of a previous
      study which showed good agreement between these methods in selected, principally
      non-septic, patients. Poor agreement was found between simultaneous TEB and
      oesophageal Doppler monitoring (ODM) estimates of baseline and acute changes in
      CO. Taken with the results of previous studies, this implies that although
      isolated ODM estimates of CO, which tend to underestimate, are less reliable, ODM
      is the preferred method to monitor acute changes in CO. For many reasons, not
      least the speed with which a large number of seriously injured soldiers could be
      assessed, ODM is probably the better method if a non-invasive estimate of CO is
      required in field hospitals.

PMID- 8758050
TI  - Thyrotoxic periodic paralysis in a Chinese population.
AB  - We retrospectively evaluated the characteristics of adult patients admitted with
      thyrotoxic hypokalaemic periodic paralysis in Hong Kong. From 1984 to 1993, 45
      Chinese adult patients were admitted with acute limb weakness, plasma potassium <
      or = 3.5 mmol/l and thyrotoxicosis confirmed by laboratory investigations. All
      but one were male. Seventy-five percent of attacks occurred between 9pm and 9am.
      Half of the attacks occurred between July and October (49.1%), most commonly in
      August (20%). Mean (+/- SEM) plasma potassium on admission was 2.17 +/- 0.08
      mmol/l (range 1.1-3.5). In 15 episodes (27.3%), plasma potassium on recovery
      exceeded 5.0 mmol/l, while in three episodes (5.5%), potassium exceeded 6.0
      mmol/l. No patient had a positive family history of thyrotoxic periodic
      paralysis. Only 28.9% had a known history of thyrotoxicosis before their first
      presentation with periodic paralysis. Twenty-seven (60%) had clinical evidence of
      thyrotoxicosis. Although all were biochemically thyrotoxic, 11.4% had only a mild
      degree of thyrotoxicosis (suppressed thyroid-stimulating hormone, high free
      thyroxine, but normal free triiodothyronine). One quarter of the patients had a
      normal erythrocyte zinc concentration, indicating either a short history of
      thyrotoxicosis or transient thyrotoxicosis. The diagnosis of thyrotoxic
      hypokalaemic paralysis should always be considered in Chinese patients with acute
      muscle weakness, especially in young males. Absence of clinical thyrotoxicosis
      does not exclude the diagnosis. Plasma potassium should be monitored carefully
      during treatment to prevent rebound hyperkalaemia.

PMID- 8758051
TI  - Respiratory insufficiency in neuronopathic and neuropathic disorders.
AB  - Twenty-nine patients with a neuronopathic or neuropathic disorder were referred
      for assessment of respiratory insufficiency between 1978 and 1994. Diagnoses
      included spinal muscular atrophy (6), chronic idiopathic demyelinating neuropathy
      (4), Vialetto-van Laere syndrome (3), hereditary motor and sensory neuropathy (3)
      and a miscellaneous group (5). We also describe seven patients with Guillain
      Barre syndrome (GBS) who required long-term ventilatory support for over 6 months
      to 7 years after the initial illness. Respiratory insufficiency occurred as a
      consequence of respiratory muscle weakness, impaired bulbar function and
      restrictive lung defects. In some groups presentation was with progressive
      nocturnal hypoventilation culminating in acute respiratory failure. Five patients
      with GBS or chronic idiopathic demyelinating neuropathy were weaned from
      ventilatory support up to 18 months after the initial illness. The remaining 24
      patients required continuous or nocturnal ventilatory support using intermittent
      positive-pressure ventilation (13), negative pressure ventilation (4), nasal-mask
      delivered intermittent positive-pressure ventilation (4), nasal-mask-delivered
      continuous positive-pressure ventilation (3), mouthpiece-assisted ventilation by
      day (2) and rocking bed (1). None have been weaned from support after a period of
      ventilation ranging from one month to 10 years. Eight patients have subsequently
      died.

PMID- 8758052
TI  - Should we use thiazide diuretics in hypertensive patients with non-insulin
      dependent diabetes mellitus?

PMID- 8758053
TI  - Radioiodine therapy for hyperthyroidism--perceptions of risk.

PMID- 8758054
TI  - Ivermectin-based control of onchocerciasis in northern Cameroon: individual
      factors influencing participation in community treatment.
AB  - A study aimed at determining individual factors associated with participation in
      community treatment with ivermectin was conducted in a village hyperendemic for
      onchocerciasis in northern Cameroon. The respective influences of sex, age, place
      of residence, distance between the compound and the dosing point, compound size,
      and participation in treatment by authoritative individuals in the compound was
      evaluated using univariate and multivariate analysis. Participation in treatment
      was closely associated with the attitude of the compound heads. Participation of
      compound heads in treatment increased as the household size increased, and as the
      distance to the distribution point diminished. This may be explained by the fact
      that getting information on health programmes is easier in large households whose
      members are involved in various social activities, and in compounds located near
      the village centre. Staff involved in health education should take this issue
      into account, and try to ensure circulation of information particularly to those
      living in small or remote compounds.

PMID- 8758055
TI  - Screening assessment of the elderly in rural Thailand by a mobile unit.
AB  - Using a mobile health unit, we conducted a survey to determine the prevalence of
      social and medical problems among an elderly population in rural Thailand. 3302
      persons aged 60 years and older from 54 villages in Mae Sot District, Tak
      Province, northern Thailand, were interviewed and examined between November 1993
      and April 1994. About 4% of those surveyed lived alone and most of them preferred
      to remain with their relatives and neighbours in the community. The proportion of
      current tobacco smokers was slightly higher in men (55.5%) than in women (51.4%).
      Men also had a higher proportion of current alcohol drinkers (20.3%) than women
      (5.3%). About 80% of the elderly reported having used medication within one month
      before the interview. Falls were the most common cause of reported injury,
      followed by cutting/piercing. The proportion of the elderly who had difficulty
      with activities of daily living was higher for women than men and increased with
      age. Meal preparation was the most common activity needing help. About 58% of
      hypertensive persons and 75% of those with diabetes were first detected during
      the survey. Some persons with treatable disorders such as senile cataract and
      dyslipidaemia were also detected by the screening programme. Geriatric screening
      assessment using mobile units may be helpful in uncovering treatable conditions
      among the elderly in rural areas.

PMID- 8758056
TI  - Occurrence of the erythrocyte band 3 (AE1) gene deletion in relation to malaria
      endemicity in Papua New Guinea.
AB  - South-east Asian ovalocytosis status was determined in 1629 individuals
      originating from 12 different geographical areas of Papua New Guinea,
      representing different ethnic groups and degrees of malaria endemicity. This was
      achieved by using polymerase chain reaction amplification to demonstrate a 27
      base pair deletion in the erythrocyte band 3 (AE1) gene. By using this method,
      the prevalence of erythrocyte band 3 gene deletion was determined to range from
      zero in both the lowland inland area of Wosera, East Sepik Province and the
      highland region of Goroka, Eastern Highlands Province to 35% on the north coast
      of Madang Province. In general, the prevalence correlated well with altitude,
      being highest on the coast where malaria transmission is high, intermediate in
      the lowlands, and lowest in the non-malarious highlands. However, Wosera, a
      lowland area in the Sepik River Plains, which is hyperendemic for malaria, was an
      exception in that no ovalocytosis was detected. These results largely confirm the
      prevalence rates that have been reported in the past using microscopy. In keeping
      with the autosomal dominant mode of inheritance, the male:female ratio was 1.02
      and no homozygote was detected, indicating that homozygosity for the ovalocytosis
      band 3 gene deletion is lethal.

PMID- 8758057
TI  - Temperature is predictive of severe malaria years in Zimbabwe.

PMID- 8758058
TI  - Anopheles oswaldoi a potential malaria vector in Acre, Brazil.

PMID- 8758059
TI  - Recrudescence of visceral leishmaniasis unrelated to HIV infection in the
      Campania region of Italy.

PMID- 8758060
TI  - Prevalence of hepatitis B antigens in human immunodeficiency virus type 1
      seropositive and seronegative pregnant women in Zambia.

PMID- 8758061
TI  - Epidemic dengue 2 in the city of Djibouti 1991-1992.
AB  - From October 1991 to February 1992, an outbreak of acute fever (in which thick
      blood films were negative for malaria) spread rapidly in the city of Djibouti,
      Djibouti Republic, affecting all age groups and both nationals and foreigners.
      The estimated number of cases was 12,000. The clinical features were consistent
      with a non-haemorrhagic dengue-like illness. Serum samples from 91 patients were
      analysed serologically for flavivirus infection (dengue 1-4, West Nile, yellow
      fever, Zika, Banzi, and Uganda-S), and virus isolation was attempted. Twelve
      strains of dengue 2 virus were isolated. Dengue infection was confirmed by a 4
      fold or greater rise in immunoglobulin (Ig) G antibody in paired serum specimens,
      the presence of IgM antibody, or isolation of the virus. Overall, 46 of the
      suspected cases (51%) were confirmed virologically or had serological evidence of
      a recent flavivirus infection. Statistical analysis showed that the presence of a
      rash was the best predictor of flavivirus seropositivity. In November 1992, Aedes
      aegypti was widespread and abundant in several districts of Djibouti city. A
      serological study of serum samples collected from Djiboutian military personnel 5
      months before the epidemic showed that only 15/177 (8.5%) had flavivirus
      antibodies. These findings, together with a negative serosurvey for dengue
      serotypes 1-4 and yellow fever virus performed in 1987, support the conclusion
      that dengue 2 virus has only recently been introduced to Djibouti.

PMID- 8758062
TI  - Bartonellosis in Zamora Chinchipe province in Ecuador.
AB  - Human bartonellosis was investigated in the Ecuadorian province of Zamora
      Chinchipe; 17 cases were identified retrospectively from hospital records over
      the period 1984-1995, mostly from 6 communities in the provincial district of
      Zumba. A questionnaire concerning risk factors for disease transmission was
      administered in these 6 communities. Blood samples were taken from individuals
      with current febrile illnesses or skin lesions suggestive of bartonellosis.
      Samples for detection of Bartonella bacilliformis were also taken from all school
      age children in communities where historical cases had been identified by
      questionnaire. No bacteriologically positive case was identified and no evidence
      of asymptomatic infection was detected. Risk factors for disease transmission,
      identified by the questionnaire, included the presence of sick or dying chickens
      and guinea-pigs. It was suggested that bartonellosis is a zoonosis with wild
      animals, probably rodents, as the reservoir. The widespread use of residual
      insecticides and the easy availability of antibiotics is likely to have modified
      the epidemiology of this disease over the last decade.

PMID- 8758063
TI  - A field trial of the ParaSight-F test for the diagnosis of Plasmodium falciparum
      infection.
AB  - The rapid manual ParaSight-F test for Plasmodium falciparum is an antigen capture
      test detecting trophozoite-derived histidine rich protein II, is simple and
      provides a definitive diagnosis within 10 min. Compared with 913 thick blood film
      examinations, the ParaSight-F test had 93.4% sensitivity and 98.2% specificity.
      Compared with 520 blood samples within the same study examined with the aid of
      the polymerase chain reaction, the ParaSight-F test had 91.6% sensitivity and
      99.4% specificity. The ParaSight-F test could be a valuable diagnostic tool for
      falciparum malaria in any situation requiring rapid diagnosis in the absence of
      microscopical examination.

PMID- 8758064
TI  - A miniature kit for the in vitro isolation of Trypanosoma brucei gambiense: a
      preliminary field assessment on sleeping sickness patients in Cote d'Ivoire.

PMID- 8758065
TI  - Use of the ProSpecT microplate enzyme immunoassay for the detection of pathogenic
      and non-pathogenic Entamoeba histolytica in faecal specimens.
AB  - A commercial microplate enzyme immunoassay (ProSpecT EIA; Alexon Inc., Sunnyvale,
      CA 94089, USA) was compared with conventional microscopy for the diagnosis of
      Entamoeba histolytica infection. Using specimens known to be infected, the
      sensitivity of the ProSpecT EIA was 78% and its specificity was 99%. No cross
      reaction with other intestinal parasites was observed. The ProSpecT EIA and
      conventional microscopy (using merthiolate-iodine-formaldehyde direct wet mounts
      and concentration techniques) were then used to detect E. histolytica infections
      in 431 patients in a mental hospital in Taiwan. Using single stool specimens,
      microscopy detected infection in 10.9% of the patients, compared with 16.9%
      detected by ProSpecT EIA. The latter method was simple and quick, but more
      expensive, and could be used to complement microscopy if a prompt diagnosis is
      desired clinically. However, ProSpecT EIA cannot differentiate between pathogenic
      E. histolytica and non-pathogenic strains (= E. dispar), which limits its
      usefulness.

PMID- 8758066
TI  - A comparison of phase contrast microscopy and an immunofluorescence test for the
      detection of Giardia spp. in faecal specimens from cattle and wild rodents.
AB  - As part of a study on the presence of Giardia cysts in water, a commercial direct
      immunofluorescence (DIF) test for the cysts was evaluated and compared to phase
      contrast microscopy. Forty faecal samples were collected from cattle; 31
      contained Giardia. All 31 samples were positive by DIF whereas only 17 were
      detected by microscopy. The detected Giardia cysts were identified as belonging
      to the G. duodenalis group. 216 faecal samples were collected from wild rodents
      (Apodemus flavicollis, A. sylvaticus and Clethrionomys glareolus); 103 contained
      Giardia. Cysts were detected in 97 samples by DIF and in 57 by microscopy; 51
      samples were positive by both methods. Nineteen rodents harboured cysts which
      morphologically resembled G. duodenalis. Specific identification was possible
      only by phase contrast microscopy, but the results suggested that DIF was
      superior for the detection of Giardia cysts in faeces of the animals tested.

PMID- 8758067
TI  - Diagnostic potential of fractionated Brugia malayi microfilarial
      excretory/secretory antigen for bancroftian filariasis.
AB  - Due to the non-availability of sufficient parasite material from Wuchereria
      bancrofti, a heterologous filarial antigen from Brugia malayi has been
      investigated for the diagnosis of bancroftian filariasis. B. malayi microfilarial
      excretory/secretory antigen (BmmfES) effectively inhibited the binding of
      circulating filarial antigen fractions (CFA2-1, 9, 11 and 12) from
      microfilaraemic cases, and of W. bancrofti microfilarial excretory/secretory
      antigen, to the immunoglobulin G (IgG) fraction of anti-filarial serum
      immunoglobulins. BmmfES was separated by ion-exchange chromatography on DEAE
      cellulose into 2 fractions, BmE DE1 and BmE DE2. BmE DE1 was marginally superior
      to whole BmmfES and BmE DE2 in detecting filarial IgG antibodies in human sera.
      230 human sera from different groups of patients were screened against BmE DE1,
      which detected specific IgG in 83% of sera from microfilaraemic donors, 83% of
      sera from patients with clinical filariasis, 17% of sera from normal residents of
      an endemic area, and in none of the sera from persons living in a non-endemic
      area. The assay system using BmE DE1, with a sensitivity of 83% and specificity
      of 83%, should be very useful in detecting microfilaraemia, particularly in
      active clinical infections where the parasite is usually not seen.

PMID- 8758068
TI  - Detection of hydatid antigen by co-agglutination in fluid samples from hydatid
      cysts.
AB  - The co-agglutination (Co-A) procedure was standardized and evaluated to detect
      hydatid antigen in fluid samples aspirated from hydatid cysts. Samples were
      collected from 14 hydatid cysts in different organs (liver, 7; lung, 5; multiple
      abdominal cysts, 1; and kidney, 1) by surgery. Echinococcus granulosus scolices
      and hooklets were seen in only 6 (42.85%) samples by routine microscopy. In
      contrast, hydatid antigen was demonstrated in all the samples by Co-A (100%
      sensitivity). Co-A could be employed as a simple and rapid diagnostic procedure,
      as an alternative to microscopy, to confirm the hydatid aetiology of a suspected
      cyst.

PMID- 8758069
TI  - Cotton wool swabs provide a convenient medium for the collection, transport and
      storage of sputum for the subsequent molecular investigation of Mycobacterium
      tuberculosis.

PMID- 8758070
TI  - The yield of acid-fast bacilli from serial smears in routine microscopy
      laboratories in rural Tanzania.
AB  - Routine results of direct examination of sputum smears for acid-fast bacilli from
      34 laboratories in Tanzania were analysed. These represented 8 regions providing
      94 laboratory-years of work; 61,580 tuberculosis suspects were evaluated with the
      aid of 141,371 smears. The average proportion of cases found among suspects was
      18.9% (range 14.3-23.8% in the 8 regions). The number of cases missed among
      suspects with incomplete examinations was calculated based on the number observed
      among suspects with a complete set of 3 smears examined, and an incremental yield
      of 83.4% with the first, 12.2% with the second, and 4.4% with the third smear was
      estimated for the total number of expected cases. These data suggest that (i) the
      method frequently employed for calculating requirements for laboratory supplies
      in low income countries, based on the estimate that 10 suspects need examination
      to identify one case of sputum smear-positive tuberculosis, is generous in the
      context of Tanzania and (ii) under routine conditions the incremental yield from
      a third smear examination after 2 negative examinations is relatively small.

PMID- 8758071
TI  - Changes in weight gain and anaemia attributable to malaria in Tanzanian children
      living under holoendemic conditions.
AB  - We investigated the effect of Plasmodium falciparum malaria on weight gain and
      haematocrit in Tanzanian children aged 6-40 months following a malaria control
      scheme which combined insecticide-impregnated bed nets with chloroquine
      chemotherapy on demand. Data from 7 villages (3 intervention and 4 control) were
      collected before, and one year after, the implementation of the programme.
      Initially, 82% of the children were parasitaemic, 78% were anaemic (i.e., packed
      cell volume < 33%) and 38% were underweight (i.e., 2 standard deviations below
      their weight-for-age Z score). One year after implementation of the programme,
      children not protected by the bed nets grew 286 g less (95% confidence interval
      [CI] 171-402 g) in a 5 months period and were twice as likely to be anaemic (95%
      CI 1.4-2.7) than were children not using impregnated bed nets. Our results
      indicated that, under holoendemic conditions, P. falciparum infection has a
      marked effect on both weight gain and anaemia.

PMID- 8758072
TI  - Electrocardiographic monitoring in severe falciparum malaria.
AB  - Electrocardiographic monitoring over 24 h was performed with 53 patients with
      severe Plasmodium falciparum malaria (11 adults and 42 children) to assess the
      frequency of unrecognized cardiac arrhythmias. Nine patients (17%) died, 5 during
      the monitoring period and 4 afterwards. Pauses lasting 2-3 s were observed in 3
      children, a single couplet in one, and a further child experienced frequent
      supraventricular ectopic beats which had not been detected clinically. In none of
      the patients who died could death be attributed to cardiac arrhythmia.
      Furthermore, no abnormality was detected which could have resulted from the often
      large doses of quinine, chloroquine or the artemisinin derivatives used for
      treatment. These results suggest that the heart is remarkably resilient even in
      the face of heavy parasite sequestration and other vital organ dysfunction, and
      that deaths from cardiac arrhythmias in severe malaria are rare. The need for
      routine cardiac monitoring of patients with severe and complicated P. falciparum
      malaria is questionable.

PMID- 8758073
TI  - Association between serum levels of reactive nitrogen intermediates and coma in
      children with cerebral malaria in Papua New Guinea.
AB  - Serum levels of reactive nitrogen intermediates (RNI; nitrate plus nitrite) were
      measured in 92 patients with cerebral malaria in the Madang Province of Papua New
      Guinea. RNI levels were compared to disease severity and clinical outcome, and
      correlated with both the depth of coma on admission and its duration. Median
      levels were higher among children with deeper coma than among those with lighter
      coma (35.6 microM vs. 16.7 microM; P = 0.008) and also among children with longer
      duration of coma (72 h; 59.3 microM vs. 19.3 microM; P = 0.004). RNI levels also
      correlated with clinical outcome, fatal cases having significantly higher RNI
      levels than survivors (41.2 microM vs. 18.5 microM; P = 0.014). Thus, high RNI
      levels are associated with indices of disease severity and may predict outcome in
      children with cerebral malaria. These data are consistent with the hypothesis
      that nitric oxide is involved in the pathogenesis of coma in human cerebral
      malaria.

PMID- 8758074
TI  - Circulating ICAM-1 levels in falciparum malaria are high but unrelated to disease
      severity.
AB  - Intercellular adhesion molecule 1 (ICAM-1) mediates the binding of Plasmodium
      falciparum to vascular endothelium. In a case-control study of falciparum malaria
      in Gambian children, we have looked for evidence that a generalized increase in
      expression of ICAM-1 is associated with cerebral malaria. Plasma levels of
      circulating ICAM-1 (cICAM-1) were significantly higher in 246 children with acute
      malaria than in 156 children with non-malarial illnesses. cICAM-1 levels
      correlated with levels of tumour necrosis factor (TNF), interleukin 1 alpha (IL-1
      alpha) and interferon gamma, supporting the view that these cytokines are
      responsible for a general upregulation of ICAM-1 expression in malaria. However,
      while it has been previously shown that TNF and IL-1 alpha levels were related to
      disease severity, this was not the case for cICAM-1. It may be that differences
      in the distribution of ICAM-1, rather than its total level of expression, are
      critical in determining the clinical outcome in malaria.

PMID- 8758075
TI  - Neutrophil leucocyte activation in severe malaria.

PMID- 8758076
TI  - Human infection by Trypanosoma rangeli in the Brazilian Amazon.

PMID- 8758077
TI  - Pyogenic liver abscesses and acute schistosomiasis mansoni: report on 3 cases and
      experimental study.
AB  - Three children with acute schistosomiasis mansoni developed pyogenic liver
      abscesses. The abscesses were diagnosed by ultrasonography and confirmed during
      laparotomy. Staphylococcus aureus were the sole bacteria isolated from the
      abscesses. An experimental study was carried out in mice to establish whether
      schistosomiasis is a predisposing cause for pyogenic liver abscesses. Seventeen
      mice (group 1) were infected with 40 Schistosoma mansoni cercariae (LE strain)
      and 60 d later inoculated intravenously with a strain of Staph. aureus, isolated
      from a patient with bacteraemia; 17 mice infected with Sch. mansoni (group 2), 19
      infected with bacteria alone (group 3), and 18 uninfected mice (group 4), served
      as controls. Thirteen group 1 mice (77%) developed multiple liver abscesses while
      none was observed in the controls. These results indicate that acute
      schistosomiasis mansoni concurrent with Staph. aureus bacteraemia favours the
      colonization of the liver by bacteria and the development of pyogenic hepatic
      abscesses.

PMID- 8758078
TI  - Bloody diarrhoea of adults in Malawi: clinical features, infectious agents, and
      antimicrobial sensitivities.
AB  - In a prospective study, 132 hospital out-patients presenting with bloody
      diarrhoea ('cases') were evaluated in Malawi, Central Africa; 73 out-patient
      tuberculosis suspects acted as controls. Most (100/132, 76%) subjects reported an
      illness lasting < or = 5 d with > 5 bowel actions in the preceding 12 h; 39/132
      (30%) reported use of systemic antimicrobial drugs in the preceding week; 57%
      (74/130) had a body mass index < 20; 4% (5/131) were febrile; and 18/130 (13%)
      had one or more sign(s) of dehydration. The 73 controls reported no diarrhoea and
      more systemic antimicrobial drug use (P = 0.0003), but were otherwise comparable
      to the subjects. All stool samples from controls and 38/124 (31%) from cases were
      macroscopically normal. Only 32% (40/124) of the cases had blood visible in the
      stool. Parasitic gut infections were found in 42/124 (34%) cases compared with
      1/60 (2%) controls (P < 0.0001). The commonest parasite was Schistosoma mansoni.
      Bacterial cultures were positive in 32/124 (26%) of the subjects. Shigella
      dysenteriae (Sd) 1 accounted for 53% (17/32) of these. All bacterial isolates
      were sensitive in vitro to nalidixic acid and ciprofloxacin, while only 18% were
      sensitive to cotrimoxazole. Sd 1 with significant antimicrobial resistance
      continues to cause seasonal epidemics of dysentery in Malawi. During these,
      approximately two-thirds of patients presenting with bloody diarrhoea have no
      blood visible in the stool. Nalidixic acid remains the drug of choice but its use
      should be restricted to patients at greatest risk of complicated shigellosis.

PMID- 8758079
TI  - Amicrofilaraemic carriers of adult Wuchereria bancrofti.
AB  - To determine the extent to which Wuchereria bancrofti infections can be detected
      in asymptomatic amicrofilaraemic men in Greater Recife, Brazil, we studied 100
      asymptomatic men who were long-term residents (> or = 15 years) of this
      filariasis-endemic area and who were amicrofilaraemic in 60 microL of capillary
      blood collected at night. Increasing amounts (1, 5, and 10 mL) of venous blood
      were collected in consecutive weeks, filtered, and examined for microfilariae; 27
      men were eventually found to be microfilariaemic and 10 remained amicrofilaraemic
      but were found to be carriers of living adult W. bancrofti by ultrasound
      examination of the scrotal area. Thus, 37% of 'amicrofilaraemic' men (in 60
      microL of blood) were found to be infected by more thorough investigation.
      Ultrasound is a valuable tool to identify adult worm infections in
      amicrofilaraemic persons, particularly for evaluation of serological assays and
      immunological studies in which the distinction between 'amicrofilaraemic adult
      worm carriers' and 'endemic normal subjects' is critical.

PMID- 8758080
TI  - Crimean-Congo haemorrhagic fever in Oman.

PMID- 8758081
TI  - Sickle cell disease and risk of peptic ulceration.

PMID- 8758082
TI  - Coagulopathy and fibrinolysis following the bite of a hump-nosed viper (Hypnale
      hypnale).

PMID- 8758083
TI  - Plasmodium falciparum: increased proportion of severe resistance (RII and RIII)
      to chloroquine and high rate of resistance to sulfadoxine-pyrimethamine in
      Peninsular Malaysia after two decades.
AB  - Uncomplicated falciparum malaria patients were randomly assigned to receive
      either 25 mg/kg chloroquine (CHL) over 3 d or a statim dose of 25 mg/kg
      sulfadoxine (SDX) plus 1.25 mg/kg pyrimethamine (PYR). Patients were followed up
      for 28 d and the parasite response graded according to World Health Organization
      criteria. Overall resistance to CHL was 63.3% and 47.4% to SDX/PYR. RI, RII and
      RIII rates were 9.1%, 42.4% and 12.1% for CHL and 10.5%, 21.1% and 15.8% for
      SDX/PYR, respectively. Degree and rates of resistance to CHL were significantly
      correlated with pre-treatment parasite density, but not those to SDX/PYR. Plasma
      CHL and SDX/PYR levels were within the reported ranges and were not significantly
      different in patients with sensitive and resistant responses.

PMID- 8758084
TI  - An open randomized trial of artemether versus quinine in the treatment of
      cerebral malaria in African children.
AB  - We have compared the efficacy of artemether versus quinine as treatment for
      cerebral malaria in children in an open randomized clinical trial in Kenya.
      Children admitted to hospital with coma and Plasmodium falciparum parasitaemia
      were treated with either intramuscular artemether (3.2 mg/kg loading dose
      followed by 1.6 mg/kg daily) or intravenous quinine (20 mg/kg loading dose
      followed by 10 mg/kg every 8 h). Both drugs were well tolerated and no
      significant adverse effect was observed. Parasite clearance times (50% and 90%)
      were shorter in patients treated with artemether (median times [h], with
      interquartile ranges in brackets, were: 50%, 7.3 [4.2-12.4] vs. 15.5 [9-22]; 90%,
      16.9 [13.2-25] vs. 28.5 [22-35]; P < 0.0001). The total mortality in 160 children
      with cerebral malaria was 16.25%, with no overall significant difference between
      the 2 treatment groups. In a subgroup of children with respiratory distress,
      mortality was higher in those treated with artemether (43.7% vs. 11.1%, P <
      0.05). The frequency of neurological sequelae and clinical recovery times were
      similar in both treatment groups. We conclude that there would currently be no
      advantage in replacing quinine with artemether for the treatment of cerebral
      malaria in African children.

PMID- 8758085
TI  - A malariometric survey in Turkana District, Kenya: chemosensitivity in vivo of
      Plasmodium falciparum infections and identity of the vector.
AB  - We have carried out a limited survey in vivo of the efficacy of chloroquine (n =
      39) and pyrimethamine-sulfadoxine (n = 29) as treatments for falciparum malaria
      in Kaling, Turkana District, northern Kenya. Both treatments were effective,
      achieving clinical cure (> 75% reduction in parasitaemia on day 2 with clinical
      improvement, and negative blood slide on day 7) in both children and adults. A
      limited entomological survey suggested that the main malaria vector in this area
      was Anopheles arabiensis.

PMID- 8758086
TI  - Fatal quinine cardiotoxicity in the treatment of falciparum malaria.

PMID- 8758087
TI  - Early clinical failures after pyrimethamine-sulfadoxine treatment of
      uncomplicated falciparum malaria.

PMID- 8758088
TI  - The effect of atovaquone (566C80) on the maturation and viability of Plasmodium
      falciparum gametocytes in vitro.
AB  - Atovaquone (566C80), a hydroxynaphthoquinone, was investigated for activity
      against Plasmodium falciparum gametocytes (NF54 strain) in vitro. After 96 h of
      continuous exposure to the drug at 1.4 x 10(-7) M (a concentration achievable in
      humans 14 d after administration of a therapeutic dose of 10 mg/kg) reductions of
      75%, 54% and 20% in the number of gametocyte stages 2, 3 and 4, respectively,
      were achieved. A small increase (14%) in stage 5 gametocytes was seen. At the
      same concentration, atovaquone showed greater activity against the asexual stages
      of P. falciparum, reductions of 93%, 96% and 43% in the number of rings,
      schizonts and trophozoites, respectively, being achieved. These data are
      consistent with inhibition of maturation of trophozoites. The observed effect on
      maturation of gametocytes is similarly consistent with blockade of gametocyte
      recruitment from merozoites produced by the preceding schizogony, or to stasis of
      intraerythrocytic sexual development before the formation of stage 2 gametocytes.

PMID- 8758089
TI  - Hyperreactive malarial splenomegaly and AIDS: proguanil prevents recurrent
      pneumonia.
AB  - An Ethiopian immigrated to Israel and gave a positive test result for human
      immunodeficiency virus. Soon after, he was thrice admitted to hospital in 3
      months for severe pneumonia. Acquired immunodeficiency syndrome was diagnosed, as
      was hyperreactive malarial splenomegaly (HMS). Thereafter, during maintained
      proguanil treatment for HMS, the patient remained well for 16 months. Then, after
      another pneumonic illness, pneumococcal vaccine was administered. Proguanil was
      maintained for another 10 months and, despite declining CD4 cell counts, good
      health continued for a further 18 months.

PMID- 8758090
TI  - Gambian trypanosomiasis and synergism between melarsoprol and eflornithine: first
      case report.

PMID- 8758091
TI  - Azithromycin prophylaxis prevents epidemic dysentery.

PMID- 8758092
TI  - Early efficacy of liposomal amphotericin B in the treatment of visceral
      leishmaniasis.
AB  - The rapidity and efficacy of a short course of liposomal amphotericin B was
      evaluated in 29 children affected by visceral leishmaniasis (Leishmania
      infantum). Their overall health status was assessed using the prognostic
      inflammatory and nutritional index (PINI), and their haematological status by the
      reticulocyte count and haemoglobin blood levels. All these quantities were
      measured on day 0, and 3 and 10 d after starting therapy. A significant decrease
      of inflammatory signs, associated with an improved reticulocyte count, was
      recorded after 3 d of therapy. A significant increase of haemoglobin levels was
      also observed 10 d after the start of treatment. The early reduction of
      inflammatory signs and the improvement of bone marrow function in most patients
      confirmed the validity of amphotericin B therapy. The PINI score is helpful in
      assessing the severity of visceral leishmaniasis and the follow-up of its
      treatment.

PMID- 8758093
TI  - Comparison of three treatment regimens with liposomal amphotericin B (AmBisome)
      for visceral leishmaniasis in India: a randomized dose-finding study.
AB  - The efficacy and safety of 3 regimens of liposomal amphotericin B (AmBisome) in
      the treatment of Indian visceral leishmaniasis were compared in a prospective
      open randomized trial. Thirty parasitologically confirmed patients were randomly
      divided into 3 equal treatment groups; group 1 received AmBisome 2mg/kg on days
      1, 2, 3, 4, 5, 6, and 10 (total dose 14 mg/kg); group 2 received AmBisome 2 mg/kg
      on days 1, 2, 3, 4, and 10 (total dose 10 mg/kg); group 3 received the same
      dosage on 1, 5 and 10 (total dose 6 mg/kg). Clinical cure resulted in all
      patients by day 24. Haemoglobin, white blood cell count, body weight and serum
      albumin level improved on day 24 and became normal by day 180. No patient
      relapsed within 12 months of follow-up. Side effects were minimal. One patient in
      group 2 died after 2 months from an unrelated disease. Liposomal amphotericin B
      is a promising new drug which is highly efficacious in the treatment of Indian
      kala-azar and produces minimal toxicity.

PMID- 8758094
TI  - Successful treatment of visceral leishmaniasis with high-dose amphotericin B
      diluted in fat emulsion: a case report.

PMID- 8758095
TI  - Correlations between specific antibody levels and urine egg counts for
      Schistosoma haematobium.

PMID- 8758096
TI  - A comparison of vaccine efficacy and mortality during routine use of high-titre
      Edmonston-Zagreb and Schwarz standard measles vaccines in rural Senegal.
AB  - Vaccine efficacy and mortality in successive cohorts of children who routinely
      received either Edmonston-Zagreb high-titre (EZ-HT) or Schwarz standard (SW-STD)
      measles vaccines have been examined in a rural area of Senegal. The 2 vaccines
      were equally protective against measles infection (vaccination efficacy: EZ-HT
      94%; SW-STD 93%). Children who did not attend a scheduled session to receive
      measles vaccine had a higher mortality rate between 9 months and 2 years of age
      than did children receiving either EZ-HT (mortality ratio [MR] = 1.81, 95%
      confidence interval [CI] 1.06-3.08) or SW-STD measles vaccine (MR = 1.74, 95% CI
      0.95-3.21). Children of either sex vaccinated with EZ-HT had lower mortality than
      their equivalents who had not received any measles vaccine. There was no
      difference in overall mortality between recipients of EZ-HT and SW-STD (MR =
      0.96, 95% CI 0.70-1.30). Using a Cox regression analysis to adjust for sex, age
      and significant background factors (season and death of mother), mortality rates
      tended to be lower for male recipients of EZ-HT than for boys receiving SW-STD
      (MR = 0.73, 95% CI 0.50-1.11) and higher for girls receiving EZ-HT than for girls
      receiving SW-STD (MR = 1.30, 95% CI 0.81-2.09) (test of interaction between sex
      and vaccine, P = 0.067). The tendency to reduced survival benefit for girls
      following receipt of high-titre measles vaccines substantiated observations from
      randomized trials in Guinea-Bissau, Senegal and Haiti. Existing data provide
      little support for the notion that high-titre vaccine is deleterious but it may
      not have the same beneficial effects as standard-titre measles vaccine.

PMID- 8758097
TI  - Acanthamoeba keratitis, contact lenses, and the potential health implications of
      global marketing.

PMID- 8758098
TI  - Blindness from quinine as an antimalarial.

PMID- 8758099
TI  - Glucantime dosage.

PMID- 8758100
TI  - Tuberculosis without tubercles.

PMID- 8758101
TI  - Tuberculosis in Siberia: 1. An epidemiological and microbiological assessment.
AB  - SETTING: Siberia, Russian Federation. OBJECTIVE: To assess the situation
      regarding tuberculosis as a paradigm for the Russian Federation. DESIGN: Data was
      obtained from official sources and through visits to dispensaries and hospitals
      in 1994. RESULTS: The downward trend in notifications of tuberculosis throughout
      Russia reversed in 1990/91, the rate increasing from 34/100,000 to 42.9/100,000
      in 1993. Incidence rates are higher in Siberia, varying from approximately 43 to
      108/100,000; prevalence is 250-300/100,000. The tuberculosis service is
      centralized and based on specialized polyclinics and dispensaries. An extensive
      surveillance system employs regular fluorography and tuberculin testing: half of
      the cases diagnosed are detected by fluorography, against 1% through contact
      tracing. Patients are classified principally on clinical and radiological
      grounds. Bacille Calmette-Guerin immunisation is performed at birth and at age 7,
      and again at 13, 21, and 28 years if Mantoux test is negative. Microscopy and
      culture services are organisationally separate, and direct comparison of smear
      and culture data is not possible. Drug resistance to isoniazid and streptomycin
      is probably high and resistance to rifampicin low, but data on susceptibility of
      isolates from new cases are not available. CONCLUSION: Tuberculosis is increasing
      in Siberia. Homelessness, unemployment and alcoholism are important factors, but
      concurrent human immunodeficiency virus (HIV) infection appears to be uncommon.
      Prisons probably form a significant reservoir of infectious cases.

PMID- 8758103
TI  - Deaths from active tuberculosis: can we rely on notification and mortality
      figures?
AB  - SETTING: Notification rates and mortality are the main indicators in the
      epidemiology of tuberculosis. While errors in case notification are known to be
      considerable, the quality of the data on deaths is largely unknown. OBJECTIVE: To
      validate the quality of data on deaths from active tuberculosis. DESIGN: We
      compared deaths from active tuberculosis in Statistics Norway with the National
      Tuberculosis Register (NTR) and cases found by autopsy in two Norwegian counties
      in 1977-1989. We also assessed the diagnostic classification and inclusion
      criteria for tuberculosis. RESULTS: 110 patients were entered into the study. We
      excluded 30 of 106 patients in Statistics Norway, primarily because of inactive
      tuberculosis (16) or minimal lesions (7). We found an additional 20 patients in
      the NTR and 14 more from autopsy reports. These missing cases were registered in
      Statistics Norway with a different diagnosis (28), inactive tuberculosis (4) or
      not found (2). Nineteen of them were diagnosed with tuberculosis by autopsy and
      five by cultures reported after death. We altered the diagnostic classification
      of underlying cause in 14% and found tuberculosis to be the underlying cause in
      65 patients. CONCLUSION: The mortality rate from active tuberculosis in
      Statistics Norway was fairly correct, but one-third were under-reported and one
      third over-reported. The mortality rate includes only half of all the deaths from
      active tuberculosis. All the cases in which active tuberculosis is mentioned on
      the death certificate are a clearer indication of tuberculosis deaths.

PMID- 8758102
TI  - Use of two methods of analysis to estimate the annual rate of tuberculosis
      infection in Southern Algeria.
AB  - SETTING: Analysis of tuberculin skin test surveys. OBJECTIVE: To estimate the
      annual tuberculous infection rate in Tamanrasset (southern Algeria) by applying
      on the one hand the classical method of the Tuberculosis Surveillance Research
      Unit (TSRU) of the International Union Against Tuberculosis, and on the other the
      study of variations of allergy published by Raj Narain et al. METHODS: 3675
      pupils aged 5-18 years were tested in October 1982 or November 1983; 1240 of them
      were tested on both occasions. The technique of the World Health Organization,
      with 2 TU PPD RT23 tuberculin was used by trained testers. The TSRU method was
      applied to the 863 children aged 5-15 years without bacille Calmette-Guerin (BCG)
      scar, according to three estimates of the prevalence of infection (cut-off points
      of the distribution of reactions of 10 mm, of 14 mm corrected by dividing by
      0.82, and mirror technique with a mode of 17 mm), and to three hypotheses of the
      decrease in infection risk (1%, 3% and 5%). The study of variations of allergy
      was used in the 1240 pupils tested twice (BCG-vaccinated or not). RESULTS: The
      average annual risk of tuberculous infection estimated by the TSRU method was
      lower than 1% (0.5%-0.6% according to the most stringent criteria). By the method
      of variations of allergy, the estimated annual infection rate was 0.9%. For the
      latter, our results are consistent with those obtained by other researchers.
      CONCLUSIONS: These findings suggest that the study of variations of allergy might
      be a good alternative approach to estimate the annual infection rate in countries
      where children are BCG-vaccinated at birth, which is the case for most developing
      countries.

PMID- 8758104
TI  - Tuberculosis in sub-Saharan Africa: a regional assessment of the impact of the
      human immunodeficiency virus and National Tuberculosis Control Program quality.
AB  - BACKGROUND: The effect of the human immunodeficiency virus (HIV) epidemic on
      tuberculosis (TB) has been evaluated for certain countries in sub-Saharan Africa.
      However, no multi-country comparisons have been performed of the magnitude of the
      changes in TB case rates and the roles of the HIV epidemic and national TB
      control program (NTP) quality in these changes. METHODS: We examined trends in TB
      case rates after 1985 for 20 sub-Saharan African countries, and also from 1975
      1984 for 10 of these countries (core countries). Average annual changes in TB
      case rates after 1985 were stratified by 1992 urban low-risk HIV seroprevalence
      and by NTP quality, as determined by a survey of international TB experts.
      RESULTS: Case rates in the core countries decreased by an average of -1.6% per
      year prior to 1985, but increased by an average of +7.0% per year after 1985
      (+7.7% per year after 1985 in all 20 countries). Average annual case rates after
      1985 increased approximately twice as fast in countries with high vs low or
      intermediate HIV seroprevalence ratings. In both the core countries and all 20
      countries, the average annual rate of rise in case rates after 1985 decreased as
      NTP quality rating increased. This relationship persisted even after
      stratification by HIV seroprevalence rating. CONCLUSIONS: TB case rates have
      increased in sub-Saharan Africa since 1985. These increases were relatively
      greater as HIV seroprevalence increased, and relatively lower as NTP quality
      increased. Improving NTP quality is essential to mitigate the resurgence of TB in
      the HIV era.

PMID- 8758105
TI  - Pulmonary tuberculosis in Guinea-Bissau: clinical and bacteriological findings,
      human immunodeficiency virus status and short term survival of hospitalized
      patients.
AB  - OBJECTIVE: To study tuberculosis patients in Guinea-Bissau with regard to
      clinical findings, bacteriologically verified diagnosis, human immunodeficiency
      virus (HIV) status and short term survival. DESIGN: 763 consecutive patients
      referred to the tuberculosis clinic with pulmonary symptoms underwent clinical
      examination and Ziehl-Neelsen sputum microscopy. Sputum for culture of
      mycobacteria on Lowenstein-Jensen medium was collected from all hospitalized
      patients, who were also screened by enzyme linked immunosorbent assay for the
      presence of HIV-1 and HIV-2 antibodies. HIV-positivity was confirmed by Western
      blot. RESULTS: 350 patients were diagnosed with tuberculosis and hospitalized.
      Adequate sputum samples were obtained from 301 patients, of whom 184 (61%) were
      positive on direct microscopy and the remaining 116 patients were diagnosed from
      clinical findings. Mycobacterium tuberculosis was cultured from 184 patients and
      M. avium in 16 patients, whereas in 101 patients the culture was negative. HIV-1
      antibodies were found in 3.0%, HIV-2 antibodies in 16.4%, and dual infections in
      2.0%. These figures, however, did not differ significantly from those of randomly
      selected age and sex matched controls. The prevalence of HIV-antibodies was
      statistically as common in patients with culture verified tuberculosis as in
      patients with clinically defined tuberculosis. Clinical acquired immunodeficiency
      syndrome was commonly diagnosed (80/301 patients) but significantly more often in
      HIV-positive, culture-positive tuberculosis patients, as were weight loss and
      lymphadenopathy. There was no statistical difference in short-time survival rate
      between the various patient groups. CONCLUSION: The diagnostic criteria applied,
      which are generally used in developing countries, identified most patients with
      pulmonary tuberculosis; however, a substantial number of patients are treated for
      tuberculosis without definite diagnostic criteria. The prevalence of HIV
      infection was high but statistically no significant difference was demonstrated
      between the patient groups, controls and patients hospitalized for diseases other
      than tuberculosis.

PMID- 8758106
TI  - Pattern of utilization of rifabutin for prophylaxis of Mycobacterium avium
      complex among patients with advanced human immunodeficiency virus disease in a
      community setting.
AB  - OBJECTIVE: To characterize the pattern of utilization, effectiveness, and safety
      profile of rifabutin for Mycobacterium avium complex (MAC) prophylaxis among
      individuals with advanced human immunodeficiency virus disease in a community
      setting. METHODS: Individuals who, while registered in the provincial drug
      distribution program, had at least one CD4 count below 100 cells/mm3 for the
      period 1 May 1993 to 31 March 1994 were included. MAC diagnoses were identified
      through a record linkage with the mycobacterial reference laboratory of the
      Provincial Centre for Disease Control. In order to determine the occurrence of
      adverse events, a survey was sent in March 1994 to the 98 primary care physicians
      prescribing rifabutin prophylaxis in the province. We achieved 100% response rate
      to the survey. RESULTS: During the study period 515 patients in our drug
      treatment program were eligible to receive MAC prophylaxis. Of these, 340 (66%)
      were being prescribed rifabutin as recommended by current guidelines. Rifabutin
      prophylaxis use was significantly associated with use of antiretroviral therapy.
      The product limit estimate of the cumulative incidence of MAC at 10 months was
      13.0% among those receiving rifabutin prophylaxis. Diagnosis of MAC was
      significantly associated with a lower baseline CD4 count (cumulative incidence
      7.1% and 18.1% for CD4 > or = 50 and < 50 cells/mm3, respectively, P = 0.01). A
      total of four cases of uveitis, eight cases of pseudo-jaundice, and five cases of
      arthralgia in 16 patients were identified by our survey. CONCLUSION: Our data
      demonstrates that rifabutin prophylaxis of MAC is being used by approximately 66%
      of eligible individuals. Rifabutin use was associated with antiretroviral use,
      which may reflect individuals' attitudes towards medications. Our intention-to
      treat analysis, with a 10 month cumulative MAC incidence of 13.0% among those
      receiving rifabutin prophylaxis, is in keeping with break-through rates
      previously reported in the context of clinical trials. Our results also support
      previous observations that the risk of MAC infection greatly increases at CD4
      counts < 50 cells/mm3. Rifabutin prophylaxis was generally well-tolerated in our
      program.

PMID- 8758107
TI  - Short course chemoprophylaxis with rifampicin, isoniazid and pyrazinamide for
      tuberculosis evaluated in gold miners with chronic silicosis: a double-blind
      placebo controlled trial.
AB  - SETTING: A medical facility for approximately 90,000 gold miners employed on 24
      South African gold mines. OBJECTIVE: To evaluate the effectiveness of rifampicin,
      isoniazid and pyrazinamide given for 3 months for the prevention of tuberculosis
      in men with silicosis. DESIGN: A randomised double-blind placebo controlled trial
      with active 4-year follow up of subjects by routine radiographic screening.
      RESULTS: A total of 382 gold miners with silicosis were randomised to receive
      rifampicin 600 mg, isoniazid 400 mg and pyrazinamide 1.25 g daily as Rifater or a
      placebo. These men have been followed for 4 years since the end of the treatment
      period. Eleven men who received the combination tablet and 15 men who received
      the placebo tablet have developed tuberculosis (chi 2 df1 = 0.66, P = 0.4).
      CONCLUSION: This multi-drug short course chemoprophylaxis regimen has failed to
      prevent tuberculosis in miners with silicosis. Even if a larger study had
      demonstrated a statistically significant effect of the regimen as compared with
      placebo, the rate of tuberculosis in the men who received the three-drug regimen
      was unacceptably high.

PMID- 8758108
TI  - Comparative histopathological study of pulmonary tuberculosis in human
      immunodeficiency virus-infected and non-infected patients.
AB  - SETTING: Clinical features of human immunodeficiency virus (HIV)-associated
      tuberculosis depend upon the patients' residual immunity. An immune-dependent
      presentation has also been described at the histopathological level in many extra
      pulmonary sites, but no descriptions have so far been made on the histopathology
      of HIV-associated pulmonary tuberculosis. OBJECTIVE: To compare the
      histopathological features of pulmonary tuberculosis in HIV-infected subjects and
      seronegative patients. DESIGN: We carried out a retrospective comparative study
      on 16 HIV-infected subjects and 16 seronegative patients with culture-proven
      pulmonary tuberculosis who underwent transbronchial biopsy. We evaluated the
      bacillary burden and the parenchymal inflammatory reaction by means of a four
      graded scoring system giving an approximate quantitative measure of the two
      parameters. RESULTS: HIV-associated pulmonary tuberculosis was found to differ
      significantly from disease forms seen in seronegative patients, with a
      significant tendency to develop highly bacillary and poorly reactive
      histopathological pictures along with the downgrading evolution of immune
      function. CONCLUSION: Pathologic features of pulmonary tuberculosis in HIV
      infected subjects differ from those encountered in seronegative patients
      depending upon the individual immunity of the former. HIV-associated progressive
      depletion of CD4+ lymphocytes leads to substantial changes in pulmonary
      reactivity to Mycobacterium tuberculosis; multibacillary pictures in a background
      of loose inflammatory reactions are quite common findings at the extreme phase of
      HIV-related immune deterioration.

PMID- 8758109
TI  - Clinical evaluation of MPT-64 and MPT-59, two proteins secreted from
      Mycobacterium tuberculosis, for skin test reagents.
AB  - SETTING: Department of Pulmonary Medicine P, Bispebjerg Hospital, Copenhagen,
      Denmark. OBJECTIVE: To study the ability of two proteins secreted from
      Mycobacterium tuberculosis, MPT-64 and MPT-59 to induce delayed type
      hypersensitivity (DTH) reactions following intradermal administration. DESIGN: In
      a small scale clinical investigation, skin reactions to these antigens were
      compared to reactions to tuberculin PPD RT23 in 1) patients with active
      tuberculosis, 2) BCG vaccinated healthy subjects with close contact with
      tuberculous patients, and 3) BCG vaccinated healthy subjects without contact with
      tuberculous patients. Tests for in vitro reactivity to these antigens were
      carried out in similar groups. RESULTS: All subjects gave positive reaction to
      tuberculin PPD RT23, whereas approximately half of the subjects in each of the
      three groups reacted to MPT-59. Two subjects (one patient with tuberculosis and
      one healthy bacille Calmette-Guerin vaccinated subject without patient contact)
      reacted to MPT-64. The studies of cell proliferation and induction of interferon
      gamma (IFN-gamma) following stimulation with tuberculin PPD and MPT-64 supported
      this profile of reactivity. CONCLUSION: None of the experimental skin test
      antigens had properties superior to tuberculin PPD RT23 in humans. The failure of
      MPT-64 to induce delayed type hypersensitivity reactions in the majority of
      tuberculosis patients is discussed, in view of the potent reactivity to MPT-64 in
      tuberculous guinea pigs.

PMID- 8758110
TI  - Differentiation of Mycobacterium species by restriction enzyme analysis of
      amplified 16S-23S ribosomal DNA spacer sequences.
AB  - SETTING: Mycobacteriology research and service laboratories in Thailand.
      OBJECTIVE: To evaluate the possibility of differentiating species of mycobacteria
      by amplifying 16S-23S ribosomal deoxyribonucleic acid (DNA) spacer and
      restriction enzyme analysis of the products. DESIGN: DNA of 113 strains of
      mycobacteria belonging to 18 species of the genus Mycobacterium were amplified by
      primers PL1 (5'-GAAGTCGTAACAAGG) and PL2 (5'-CAAGGCATCCACCAT). The amplified
      products as well as their HaeIII-, MspI- and BstXI-digested products were
      visualized after agarose gel electrophoresis. RESULTS: The amplified products of
      rapid-growing mycobacteria were different from the slow-growing mycobacteria. The
      restriction profiles of members of M. tuberculosis complex were the same as each
      other but different from other investigated species. The restriction profiles of
      some species, such as M. avium, M. intracellulare and M. gordonae, were unique,
      while those of the other species had more than one pattern. However, the
      restriction profiles of most investigated species were different from each other.
      CONCLUSION: This preliminary study suggested that the method might be useful for
      species differentiation of some commonly isolated pathogenic mycobacteria.

PMID- 8758111
TI  - Use of DNA restriction fragment typing in the differentiation of Mycobacterium
      tuberculosis complex isolates from animals and humans in Burundi.
AB  - SETTING: Bubanza Hospital and Veterinary Laboratory in Bujumbura, Burundi.
      OBJECTIVE: To monitor the rate of Mycobacterium bovis infections among
      tuberculosis (TB) patients and among slaughtered cattle, and to analyse the
      polymorphism among deoxyribonucleic acid (DNA) fingerprints of the M.
      tuberculosis complex isolates. DESIGN: 135 lymph node biopsies and 35 sputum
      specimens from human patients, together with specimens from 46 healthy animals
      and 36 animals suspected for bovine tuberculosis (BTB), were cultured. Isolates
      were identified phenotypically and DNA fingerprints were obtained by IS6110 based
      restriction fragment length polymorphism. RESULTS: 119 M. tuberculosis complex
      isolates were obtained from 170 human specimens. M. bovis was not identified in
      any human sample. One out of 46 healthy animals and 14 out of 36 BTB suspected
      animals yielded M. bovis isolates. DNA fingerprinting revealed four to eight
      copies of IS6110 for all M. bovis isolates with some degree of polymorphism, and
      some clustering for human TB isolates. No relationship was observed between human
      and bovine isolates. CONCLUSION: At present M. bovis seems to play a minor role
      in human TB in Burundi, despite the high prevalence of both human
      immunodeficiency virus infection in humans and M. bovis in cattle. DNA
      fingerprinting is able to differentiate between bovine isolates.

PMID- 8758112
TI  - Lymph node swelling due to bacille Calmette-Guerin vaccination with multipuncture
      method.
AB  - SETTING: In the mass bacille Calmette-Guerin (BCG) vaccination programme using
      the multipuncture method practised in Japan for young children, lymph node
      swelling is a not uncommon complication and its management is sometimes
      unnecessarily radical. OBJECTIVES: To determine the frequency of lymphadenitis
      after BCG vaccination with the multipuncture method, and to describe its clinical
      features. DESIGN: A total of 34,516 children aged 0-3 years, who received primary
      vaccination with BCG between 1985 and 1989, were observed for the occurrence of
      lymphadenopathy. Oral explanation was given to the parents about lymph node
      swelling, and a postcard with a reporting form was given, to be returned if any
      lymph node swelling was observed in the baby. The parents were then contacted,
      and invited to our clinic for further observation. Cases with one or more swollen
      nodes greater than 7 mm were included in this analysis as cases of
      lymphadenopathy. RESULTS: The frequency of lymphadenopathy was 0.73% (95% CI 0.65
      0.83). Babies under 1 year of age had higher incidence. Lymph nodes greater than
      10 mm were seen among 0.40% of babies, with a higher rate among boys than in
      girls (0.95% and 0.50%, respectively). Sixty-five percent of the cases were first
      noticed 4-6 weeks after vaccination; others were detected before or after that
      period. Nineteen percent of the cases had multiple swollen nodes, and 2% had
      adenitis only outside the axilla. Eight cases progressed to suppurative adenitis
      with rupture, comprising 0.02% (95% CI 0.012%-0.046%) of those vaccinated. In the
      remaining cases the swelling subsided quickly (92% within 2 months and the others
      later), with no medical or surgical treatment.

PMID- 8758113
TI  - Tuberculosis in the community: 1. Evaluation of a volunteer health worker
      programme to enhance adherence to anti-tuberculosis treatment.
AB  - SETTING: A voluntary health worker project (Operation Elsies River) was started
      in a high incidence tuberculosis (TB) area in the Western Cape of South Africa,
      in order to assist the local TB Control programme with case-holding. OBJECTIVE:
      To evaluate the effectiveness of this group of volunteers in enhancing adherence
      of notified TB patients to tuberculosis treatment. DESIGN: A cohort study was
      conducted with 351 TB patients (203 children and 148 adults). RESULTS: The data
      from the child and the adult groups were analysed separately. The child group was
      more adherent to TB treatment than adults. The supervision option with staff
      dedicated to the treatment of TB, such as the clinic and the SANTA creche,
      achieved better adherence results for pre-school children. The supervision
      modalities for adults did not differ in their adherence performance even
      following adjustment for confounders. CONCLUSION: The supervision option provided
      by the volunteers did not significantly improve the adherence of adult patients
      to antituberculosis treatment.

PMID- 8758114
TI  - Polymerase chain reaction for non-invasive diagnosis of brain mass lesions caused
      by Mycobacterium tuberculosis: report of five cases in human immunodeficiency
      virus-positive subjects.
AB  - To investigate whether the polymerase chain reaction (PCR) on the IS6110 sequence
      of Mycobacterium tuberculosis could permit the early and non-invasive diagnosis
      of tuberculous brain lesions without meningeal involvement in acquired
      immunodeficiency virus patients, we examined retrospective cerebrospinal fluid
      (CSF) samples from five patients diagnosed as having cerebral lesions caused by
      M. tuberculosis. M. tuberculosis deoxyribonucleic acid was detected in CSF
      samples obtained from each of the patients studied, but in none of the controls.
      The PCR results coincided with M. tuberculosis isolation from CSF in two
      patients. In an additional two subjects, culture for M. tuberculosis on CSF was
      negative, and the diagnosis of central nervous system tuberculosis was achieved
      by response to specific therapy. In the last patient the PCR result on CSF was
      confirmed by isolation of M. tuberculosis from brain biopsy. Interestingly, in
      this patient the CSF did not yield M. tuberculosis isolation when cultured. The
      data show the value of PCR as a potentially useful approach for the early and
      rapid diagnosis of cerebral tuberculosis even without meningitis.

PMID- 8758115
TI  - Lymph node biopsy as an aid in the diagnosis of intracranial tuberculosis.
AB  - This report describes five patients with intracranial tuberculosis (TB): four
      with tuberculous meningitis and one with intracranial tuberculomas. In all cases
      the diagnosis was confirmed by excision biopsy of an enlarged cervical or
      axillary lymph node. The biopsies showed caseating granulomas and acid fast
      bacilli, confirming the diagnosis of TB within 48 h of admission. Lymphnode
      biopsies may be an effective and practical aid in diagnosing intracranial TB.

PMID- 8758116
TI  - Bronchopulmonary infection with Mycobacterium malmoense presenting as a
      bronchoesophageal fistula.
AB  - We report a bronchopulmonary infection with Mycobacterium malmoense in a patient
      with severe immunosuppression due to insulin-dependent diabetes mellitus, humoral
      immunodeficiency after thymoma (Good's syndrome) and prolonged immunosuppressive
      treatment after myasthenic crisis. It presented as non-resolving pneumonia of the
      left lower lobe. Bronchoscopically, a bronchoesophageal fistula was detected.
      Numerous acid-fast organisms were found in the sputum specimen and in the
      bronchial biopsy around the fistula. M. malmoense was isolated from sputum,
      bronchoalveolar lavage and bronchial biopsy. Whereas conventional in vitro
      susceptibility testing revealed susceptibility only to ethambutol, multi-drug
      susceptibility testing confirmed susceptibility to rifampicin, ethambutol,
      clarithromycin and prothionamide. The clinical outcome after 12 months of therapy
      resulted in a stable remission and considerable suppression of the mycobacterial
      load, but not in complete eradication.

PMID- 8758117
TI  - Serological diagnosis of tuberculosis employing lipooligosaccharide antigen in
      developing countries.

PMID- 8758118
TI  - The phylogeny of Mycobacterium tuberculosis.

PMID- 8758119
TI  - The application of empiric antituberculosis treatment.

PMID- 8758121
TI  - Dilated cardiomyopathy.

PMID- 8758122
TI  - Nitric oxide production in critically ill patients.
AB  - OBJECTIVE: To measure serum nitrite and nitrate levels in critically ill children
      as indicators of endogenous nitric oxide (NO) production. HYPOTHESIS: Endogenous
      NO production is increased in children with conditions characterised by immune
      stimulation. DESIGN: Prospective descriptive study in a multidisciplinary
      paediatric intensive care unit. PATIENTS: 137 consecutive critically ill children
      with a variety of clinical conditions. INTERVENTIONS: Using a rapid microtitre
      plate technique, daily serum nitrite and nitrate levels were measured from serum
      samples that remained in the clinical laboratory after daily routine phlebotomy.
      Clinical and laboratory information was also gathered daily for each patient.
      RESULTS: The maximum serum nitrite plus nitrate levels (microM) reached by
      children with infection (41.8 (SD 18.1)), sepsis syndrome (85.1 (39.9)), shock
      without sepsis (36.4 (19.1)), transplantation alone (61.0 (43.4)),
      transplantation with sepsis (200.7 (150.5)), or rejection (161.7 (70.4)), were
      higher than in controls (18.1 (9.3)). In the absence of exogenous NO donors,
      levels greater than 80 microM were reached only in children with the sepsis
      syndrome, organ transplantation, or acute rejection. CONCLUSIONS: Increased
      endogenous NO production occurs in children with clinical conditions associated
      with immune stimulation. Further investigation is warranted to determine the
      value of this simple and rapid test as a clinically useful diagnostic tool and
      therapeutic monitor in the evaluation of children at risk for the sepsis syndrome
      or acute allograft rejection.

PMID- 8758120
TI  - L-Carnitine.

PMID- 8758123
TI  - Accelerated pubertal development in patients with shunted hydrocephalus.
AB  - OBJECTIVE: To evaluate pubertal development and peripheral concentrations of
      gonadotrophins and sex hormones in children with shunted hydrocephalus compared
      with healthy controls. STUDY DESIGN: 114 patients (52 females, 62 males) and 73
      healthy controls (35 females, 38 males) aged 5 to 20 years were analysed for
      stage of puberty, age at menarche, testicular volume, basal serum follicle
      stimulating hormone (FSH), luteinising hormone (LH), sex hormone binding globulin
      (SHBG), testosterone and oestradiol concentrations, and free androgen index.
      RESULTS: Male gonadal and male and female pubic hair development occurred
      significantly earlier in the patients than in the controls. The mean age at
      menarche was significantly lower in the female patients than in their controls
      (11.7 v 13.2 years; p < 0.001), and lower than it had been for their mothers (v
      13.1 years; p < 0.001). Relative testicular volume was higher in the male
      patients than in their controls (1.2 standard deviation score (SDS) v 0.2 SDS; p
      < 0.001). The prepubertal patients had higher basal LH (0.13 U/l v 0.08 U/l; p <
      0.001) and SHBG (132.3 nmol/l v 109.1 nmol/l; p < 0.01) than the controls. Both
      the prepubertal and pubertal females had significantly higher basal FSH than
      their controls (1.57 U/l v 1.03 U/l; p < 0.05, and 4.0 U/l v 2.9 U/l; p < 0.01,
      respectively). CONCLUSIONS: Hydrocephalic children experience accelerated
      pubertal maturation, reflected in a younger age at menarche in females and an
      increased testicular volume in males. This may be because of enhanced
      gonadotrophin secretion, possibly resulting from unphysiological variations in
      intracranial pressure.

PMID- 8758124
TI  - Osteocalcin, growth, and inhaled corticosteroids: a prospective study.
AB  - OBJECTIVES: To determine the relationship between biochemical markers of bone
      metabolism and statural growth, and their suitability as surrogate markers of
      inhaled corticosteroid induced growth suppression. DESIGN: Randomised, double
      blind, placebo controlled comparison of inhaled beclomethasone dipropionate 200
      micrograms twice daily as dry powder for six months. SETTING: Southampton.
      OUTCOME MEASURES: Serum osteocalcin, urinary deoxypyridinoline, and statural
      growth. SUBJECTS: 7 to 9 year old children with recurrent wheeze. RESULTS: There
      were no significant differences in serum osteocalcin between the beclomethasone
      dipropionate and placebo group measured at baseline or after three and six
      months' treatment, while deoxy-pyridinoline was significantly higher in the
      placebo treated children after three months. Growth was significantly decreased
      in the beclomethasone dipropionate group over the course of the study. Growth
      over the six months, both in those receiving beclomethasone dipropionate and
      those receiving placebo, was significantly correlated with serum osteocalcin
      measured at three months and six months. CONCLUSION: Although serum osteocalcin
      shows excellent correlation with growth, it is a poor marker for decreased growth
      associated with use of inhaled corticosteroids.

PMID- 8758125
TI  - Factors affecting prepubertal growth in homozygous sickle cell disease.
AB  - OBJECTIVE: To investigate the role of haematological indices, socioeconomic
      status, and morbidity in prepubertal growth in homozygous sickle cell (SS)
      disease. METHOD: Height, weight, and haematology were serially recorded in a
      cohort study of 315 children with SS disease from birth to 9 years at the sickle
      cell clinic of the University Hospital of the West Indies, Kingston, Jamaica.
      RESULTS: Height increment between 3 and 9 years correlated positively with total
      haemoglobin at age 7 years in boys but not girls. Attained height and weight at
      age 7 years correlated positively with haemoglobin and fetal haemoglobin in boys
      but not girls. Only the correlation between haemoglobin and weight showed a
      significant gender difference. Partial correlation analysis suggested that the
      effect of haemoglobin was accounted for by the effect of fetal haemolglobin and
      further analysis indicated that height correlated with F reticulocyte count (a
      measure of fetal haemoglobin production) in both sexes but not with the ratio of
      F cells to F reticulocytes (a measure of F cell enrichment). Growth was not
      significantly related to mean red cell volume, proportional reticulocyte count,
      alpha thalassaemia, socioeconomic status, or morbidity. CONCLUSION: A high
      concentration of fetal haemoglobin in boys with SS disease is associated with
      greater linear growth. It is postulated that in boys, low concentrations of fetal
      haemoglobin increase haemolysis and hence metabolic requirements for
      erythropoiesis, putting them at greater risk of poor growth. Differences in the
      relationship of haematology and growth between boys and girls with SS disease
      dictate that future analyses of growth take gender into account.

PMID- 8758126
TI  - Differential cytology of bronchoalveolar lavage fluid in immunosuppressed
      children with pulmonary infiltrates.
AB  - OBJECTIVE: Bronchoalveolar lavage (BAL) is a well established technique for the
      detection of pathogens in immunosuppressed children, but its diagnostic yield is
      variable. The aim of this study was to investigate whether BAL differential cell
      counts are helpful in the evaluation of pulmonary infiltrates in
      immunocompromised children. STUDY DESIGN: BAL was performed 28 times in 27
      febrile immunocompromised children with pulmonary infiltrates. All patients were
      pretreated with broad spectrum antibiotics; 11 children also received
      amphotericin B. BAL was conducted with a flexible bronchoscope wedged in the area
      of maximal pathology as suggested by the chest radiograph or in the middle lobe
      in patients with diffuse interstitial radiographic changes. Differential cell
      counts were performed from cell smears obtained after centrifugation of BAL
      fluid. RESULTS: Bacterial or fungal organisms were detected in BAL fluid of 12
      patients. Patients with bacterial or fungal infections (group 1) had a
      significantly higher percentage of granulocytes in BAL fluid both compared with
      patients with sterile BAL cultures (group 2) and with a control group of children
      without pulmonary disease (p < 0.001, Wilcoxon test). The proportion of
      lymphocytes was not different from the control group in group 1 but significantly
      increased in group 2 (p < 0.001, Wilcoxon test). Blood differential cell counts
      were not different in the two patient groups. Lymphocyte subsets of BAL fluid
      obtained in a subgroup of patients were not significantly different from
      controls. CONCLUSION: These data suggest that BAL differential cell counts may be
      a useful adjunct in the differential diagnosis of pulmonary infection in
      immunocompromised children.

PMID- 8758127
TI  - Assessment of pulmonary mechanics and breathing patterns during posturally
      induced glossoptosis in infants.
AB  - Respiratory mechanics were studied in nine infants with glossoptosis-apnoea
      syndrome to determine whether glossoptosis may account for signs of both
      inspiratory and expiratory airway obstruction. Airflow, oesophageal pressure,
      inspiratory and expiratory time (Ti and Te), and inspiratory and expiratory
      resistance (Ri and Re) were measured before and during ventilatory phases
      characterised by glossoptotic pharyngeal obstruction, induced by turning the
      infants onto their backs. In addition, an attempt was made to correlate the
      abnormalities in pulmonary mechanics with the clinical features. During partial
      glossoptotic pharyngeal obstruction, a significant increase was observed in Te
      and Re and variable changes in Ti and Ri. During severe obstruction, the infants
      displayed obstructed inspiratory efforts often associated with stridor, as well
      as obstructed expiratory efforts often associated with audible grunting and
      retarded expiratory flow pattern. The expiratory grunt was loudest over the neck
      and mimicked bronchospasm over the chest. These findings indicate that
      glossoptotic pharyngeal obstruction induces functional airway obstruction which
      may affect both inspiration and expiration. Expiratory airway obstruction seems,
      at least in part, to be due to active braking of expiratory flow.

PMID- 8758128
TI  - Predictive value of preschool surveillance in detecting learning difficulties.
AB  - OBJECTIVES: The Hall report specified the early detection of mild to moderate
      learning difficulties as one aim of child health surveillance (CHS). This study
      examines the efficacy of preschool CHS in the early recognition of children with
      these disorders. DESIGN: A retrospective case-control study. SUBJECTS: All
      children (n = 408) with mild to moderate learning difficulties born between 1
      July 1983 and 30 June 1984 and resident in North and West Belfast. CONTROLS: 2406
      birth records and 150 full child health records controlled for age and
      geographical area. RESULTS: The prevalence of mild to moderate learning
      difficulties in North and West Belfast was 16%. Only 6% of children with learning
      difficulties were identified by the CHS in the preschool period, although the
      detection rate for children eventually requiring placement in schools for
      moderate learning difficulties was better. Coverage of the CHS ranged from 90% at
      the 2 year examination to 98% at the 4 year examination. Perinatal variables
      associated with learning difficulties after multiple logistic regression analysis
      were lower social class (odds ratio (OR) 3.9), prematurity < 35 weeks (OR 3.0),
      male sex (OR 1.6), and birth to an unmarried mother (OR 0.6). Independent
      preschool variables identified by the CHS were speech delay (OR 3.3), poor
      parenting skills (OR 4.0), behaviour problems (OR 2.8), enuresis (OR 2.4), poor
      visual acuity (OR 1.8), and otitis media with effusion (OR 1.4). A statistical
      model for the early detection of learning difficulties using these risk factors
      is unable to predict accurately the children who will develop mild to moderate
      learning difficulties. CONCLUSIONS: The CHS as it existed from 1983 to 1989 in
      North and West Belfast was poorly sensitive to the detection of mild to moderate
      learning difficulties despite excellent coverage. An accurate predictive model
      for learning difficulties could not be developed from the risk factors documented
      by the CHS.

PMID- 8758129
TI  - A study of bereavement care after a sudden and unexpected death.
AB  - Bereaved parents' perceptions of care after the sudden, unexpected death of their
      child (from 1 week to 12 years), and the care that was or could be offered by
      statutory and voluntary agencies, was assessed in 11 health districts in seven
      regions of England and Wales. In these 11 districts, 185 families were identified
      who met the criteria of the study. Permission to contact these families was given
      by only 72 general practitioners. Of these, 42 families responded (58%). Sudden
      infant death syndrome accounted for 43% of the deaths. The results from postal
      questionnaires sent to both parents showed that hospital care was perceived as
      good on the whole, although parents would like more choices. Most parents felt
      that community care was inadequate, leaving many feeling isolated. In contrast,
      questionnaires from health visitors and general practitioners in the same health
      districts showed that they believed that they were the most appropriate
      professionals to give follow up care, but as there were few policies to guide
      them and little training provided, felt unable to offer support.

PMID- 8758130
TI  - Treatment of hypogammaglobulinaemia with intravenous immunoglobulin, 1973-93.
AB  - AIMS: To review the results of long term high dose intravenous immunoglobulin
      treatment. METHODS: 162 treatment years in 18 patients with
      hypogammaglobulinaemia who received intravenous immunoglobulin treatment between
      1973 and 1993 were reviewed. RESULTS: A mean dose of 0.42 g/kg immunoglobulin
      resulted in a mean trough IgG concentration on the 23.5th centile for age. The
      subjects enjoyed a good standard of health. Infection rates were similar to the
      general paediatric population and a similar pattern of infections occurred. There
      were only 0.06 episodes of pneumonia and 0.11 hospital admissions per year of
      treatment. The development of chronic pulmonary disease was significantly related
      to trough IgG concentrations less than the 10th centile (p < 0.009), however,
      this developed in only two children after the start of treatment. All children
      had normal growth parameters. Adverse reactions to immunoglobulin infusions
      reduced from 9.1% to 0.8% after the introduction of low pH modified intravenous
      immunoglobulin in 1986. Although minor, transient increases in liver transaminase
      values were common; none of the 11 patients tested by hepatitis C polymerase
      chain reaction were positive. CONCLUSION: Children with hypogammaglobulinaemia
      who are receiving replacement treatment grow normally and have an infection rate
      similar to that of non-immunodeficient children. No evidence of transmission of
      hepatitis C virus by the Commonwealth Serum Laboratories immunoglobulin was
      found.

PMID- 8758131
TI  - How much coughing is normal?
AB  - A new multiparametric device (RBC-7) was used for recording cough in ambulatory
      children over a 24 hour period. The number of coughs and the pattern of coughing
      can easily be studied with the aid of a personal computer and dedicated computer
      software. Forty one 'normal' children were recorded, identified from a primary
      school with the aid of a questionnaire. They were free from any respiratory
      infection for one month, and had a normal examination and spirometry immediately
      before recording. Cough frequency was 11.3, range 1 to 34, cough episodes per 24
      hours. This was unaffected by passive smoking or the presence of furry pets in
      the home. Nocturnal and prolonged coughing was unusual in these children. The
      device was highly acceptable to the children, and no adverse effects were
      reported. Such objective data on cough outside the laboratory setting are unique,
      help to determine what is normal, and may help in the diagnosis and assessment of
      many respiratory diseases.

PMID- 8758132
TI  - Sputum induction for the diagnosis of tuberculosis.
AB  - Confirmation of tuberculosis in young children is difficult as they seldom
      expectorate sputum. Gastric aspirates are invasive and stressful and like
      laryngeal swabs are seldom smear positive. Induction of sputum by nebulised
      hypertonic saline (3%) was attempted in 30 Malawian children aged 3-15 years and
      was successful in 29. Four sputa were smear positive and Mycobacterium
      tuberculosis was cultured from three of them. A further four sputa were culture
      positive though smear negative. In all, the diagnosis of tuberculosis was
      confirmed in eight (28%) of 29 children. The presence of polymorphonuclear cells
      in the specimen was indicative of sputum, in contrast to epithelial cells which
      originate from saliva. A predominance of polymorphonuclear cells in specimens was
      more common in older children and these specimens were more likely to be smear
      positive or culture positive. Sputum induction is a useful method for the
      confirmation of tuberculosis and is possible in young children.

PMID- 8758133
TI  - Placental weight, birth measurements, and blood pressure at age 8 years.
AB  - OBJECTIVE: To examine relationships between blood pressure during childhood and
      both placental weight and body size at birth, in an Australian population.
      DESIGN: A follow up study of a birth cohort, undertaken when cohort members were
      aged 8 years. SETTING: Adelaide, South Australia. SUBJECTS: 830 children born in
      the Queen Victoria Hospital in Adelaide, South Australia, during 1975-6. MAIN
      OUTCOME MEASURES: Systolic and diastolic blood pressure measured when the
      children were aged 8 years. RESULTS: Blood pressure at 8 years was positively
      related to placental weight and inversely related to birth weight, after
      adjusting for the child's current weight. For diastolic pressure there was a
      decrease of 1.0 mm Hg for each 1 kg increase in birth weight (95% confidence
      interval (CI) = -0.4 to 2.4) and an increase of 0.7 mm Hg for each 100 g increase
      in placental weight (95% CI = 0.1 to 1.3). Diastolic pressure was also inversely
      related to chest circumference at birth, independently of placental weight, with
      a decrease of 0.3 mm Hg for each 1 cm increase in chest circumference (95% CI =
      0.2 to 0.5). CONCLUSIONS: These findings are further evidence that birth
      characteristics, indicative of fetal growth patterns, are related to blood
      pressure in later life.

PMID- 8758134
TI  - 3-Phosphoglycerate dehydrogenase deficiency: an inborn error of serine
      biosynthesis.
AB  - Serine concentrations were markedly decreased in the cerebrospinal fluid of two
      brothers with congenital microcephaly, profound psychomotor retardation,
      hypertonia, epilepsy, growth retardation, and hypogonadism. The youngest boy also
      had congenital bilateral cataract. Magnetic resonance imaging of the brain showed
      evidence of dysmyelination. Plasma serine as well as plasma and cerebrospinal
      fluid glycine concentrations were also decreased but to a lesser extent.
      Treatment with oral serine in the youngest patient significantly increased
      cerebrospinal fluid serine and abolished the convulsions. In fibroblasts of both
      patients, a decreased activity was demonstrated of 3-phosphoglycerate
      dehydrogenase, the first step of serine biosynthesis (22% and 13% of the mean
      control value). This is an unusual disorder as the great majority of
      aminoacidopathies are catabolic defects. It is a severe but potentially treatable
      inborn error of metabolism that has not been previously reported in man.

PMID- 8758135
TI  - Uncooked cornstarch--efficacy in type I glycogenosis.
AB  - Uncooked cornstarch (UCCS) loads in 14 patients with type 1 glycogenosis revealed
      that satisfactory glycaemia was achieved for a median of 4.25 hours (range 2.5 to
      6). Length of glycaemia was related weakly to UCCS dose, but not to patient age
      or measures of metabolic control. Careful monitoring is required during UCCS
      treatment.

PMID- 8758136
TI  - X linked agammaglobulinaemia with a 'leaky' phenotype.
AB  - Typical X linked agammaglobulinaemia (XLA) is characterised by absence of
      immunoglobulin production and lack of mature B cells. The gene responsible for
      XLA has recently been identified, and codes for a B cell tyrosine kinase, BTK. A
      family affected by a B cell immunodeficiency, which is less severe than classical
      XLA, is described but they had a pedigree suggestive of X linked inheritance.
      Demonstration of a mutation in the BTK gene confirms that this is a mild form of
      XLA.

PMID- 8758137
TI  - Disclosure of Duchenne muscular dystrophy after newborn screening.

PMID- 8758138
TI  - Predicting the distribution of tsetse flies in West Africa using temporal Fourier
      processed meteorological satellite data.
AB  - An example is given of the application of remotely-sensed, satellite data to the
      problems of predicting the distribution and abundance of tsetse flies in West
      Africa. The distributions of eight species of tsetse, Glossina morsitans, G.
      longipalpis, G. palpalis, G. tachinoides, G. pallicera, G. fusca, G. nigrofusca
      and G. medicorum in Cote d'Ivoire and Burkina Faso, were analysed using
      discriminant analysis applied to temporal Fourier-processed surrogates for
      vegetation, temperature and rainfall derived from meteorological satellites. The
      vegetation and temperature surrogates were the normalized difference vegetation
      index and channel-4-brightness temperature, respectively, from the advanced, very
      high-resolution radiometers on board the National Oceanic and Atmospheric
      Administration's polar-orbiting, meteorological satellites. For rainfall the
      surrogate was the Cold-Cloud-Duration (CCD) index derived from the geostationary,
      Meteosat satellite series. The presence or absence of tsetse was predicted with
      accuracies ranging from 67%-100% (mean = 82.3%). A further data-set, for the
      abundance of five tsetse species across the northern part of Cote d'Ivoire (an
      area of about 140,000 km2), was analysed in the same way, and fly-abundance
      categories predicted with accuracies of 30%-100% (mean = 73.0%). The thermal data
      appeared to be the most useful of the predictor variables, followed by vegetation
      and rainfall indices. Refinements of the analytical technique and the problems of
      extending the predictions through space and time are discussed.

PMID- 8758139
TI  - The ecology of malaria--as seen from Earth-observation satellites.
AB  - Data from sensors on board geostationary and polar-orbiting, meteorological
      satellites (Meteosat and NOAA series) are routinely obtained free, via local
      reception systems, in an increasing number of African countries. Data collected
      by these satellites are processed to produce proxy ecological variables which
      have been extensively investigated for monitoring changes in the distribution and
      condition of different natural resources, including rainfall and vegetation
      state. How these data products (once incorporated, along with other data, into a
      geographical information system) could contribute to the goals of monitoring
      patterns of malaria transmission, predicting epidemics and planning control
      strategies is the subject of the present review. By way of illustration, an
      analysis of two of these products, normalized difference vegetation index (NVDI)
      and cold-cloud duration (CCD), is given in conjunction with epidemiological and
      entomological data from The Gambia, a country where extensive studies on malaria
      transmission have been undertaken in recent years. Preliminary results indicate
      that even simple analysis of proxy ecological variables derived from satellite
      data can indicate variation in environmental factors affecting malaria
      transmission indices. However, it is important to note that the associations
      observed will vary depending on the local ecology, season and species of vector.
      Whilst further quantitative research is required to validate the relationship
      between satellite-data products and malaria-transmission indices, this approach
      offers a means by which detailed knowledge of the underlying spatial and temporal
      variation in the environment can be incorporated into a decision-support system
      for malaria control.

PMID- 8758140
TI  - Malaria in pregnancy: efficacy of a low dose of mefloquine in an area holoendemic
      for multi-drug resistant Plasmodium falciparum.
AB  - Thirty-three pregnant women with pure P. falciparum parasitaemias (> or = 10(3)
      parasites/microliters blood), were each treated with a single, oral dose (12.5
      mg/kg body weight) of mefloquine base (MQ), at Ahmadu Bello University Teaching
      Hospital, Zaria urban area, Nigeria. All 33 women were aparasitaemic by day 6
      post-treatment and none became parasitaemic during the remaining 21 days of
      observation. Minimal side-effects were reported by the patients. The mean (S.D.)
      fever- and parasite-clearance times were 48 (17) and 50 (26) h, respectively. In
      standard microtests in vitro, schizont maturation was inhibited with MQ at 16
      pmol/well (3.2 pmol/microliters). These findings indicate that, at least in the
      study area, semi-immune, pregnant women have high tolerability to relatively low
      doses of MQ and that such doses are fully effective against the local P.
      falciparum isolates.

PMID- 8758142
TI  - Multiple infection with Plasmodium and helminths in communities of low and
      relatively high socio-economic status.
AB  - A study was conducted in the city of Lubumbashi, Zaire: (1) to survey parasitic
      infections and clinical conditions in the local children and their mothers; (2)
      to identify combinations of parasites and clinical conditions that commonly
      occurred together in individuals; and (3) to determine whether single- and/or
      multiple-species infections were risk determinants of the observed clinical
      conditions. Overall, 1100 children and mothers from three subdivisions, two of
      low socio-economic status (LSES) and one of relatively high socio-economic status
      (HSES), provided stool and blood samples and were clinically examined. Plasmodium
      prevalence was higher in the two LSES subdivisions than in the HSES subdivision.
      Prevalence and intensity of Ascaris lumbricoides infection were low in the HSES
      subdivision and one of the two LSES subdivisions. In contrast, prevalence and
      intensity of Trichuris trichiura and of hookworms were similar in all
      subdivisions. Plasmodium and A. lumbricoides were the most frequently found
      single-species infections. The combination of A. lumbricoides and Plasmodium was
      the most frequent double-species infection and that of A. lumbricoides,
      Plasmodium and T. trichiura was the most frequent triple-species infection.
      Significant positive associations between parasite species were detected in the
      HSES subdivision, and in one of the two LSES subdivisions. Because the
      relationships were not consistently detected, it is hypothesized that the
      associations are determined by environmental conditions rather than synergy
      between the parasites in the host. The most commonly observed clinical conditions
      were abdominal pain, diarrhoea, fever, and low packed-cell volume (PCV). The
      occurrence of each was significantly lower in the HSES subdivision than in at
      least one of the two LSES subdivisions. Abdominal pain and low PCV were most
      common in individuals presenting with only a single clinical condition, and the
      combination of this symptom and sign was the most commonly observed pair of
      conditions. Abdominal pain, low PCV and diarrhoea was the most common combination
      in individuals with three clinical conditions. Logistic regression revealed that
      hookworm infection, T. trichiura infection, young age and residence in an LSES
      subdivision were determinants of diarrhoea. Trichuris trichiura infection, young
      age and living in an LSES subdivision were risk factors for abdominal pain.
      Plasmodium infection and young age were risk factors for fever. LSES was the only
      predictor of low PCV. Infection with A. lumbricoides did not enter any of the
      models. No significant interactions were detected among parasites, indicating
      that there was no synergism or antagonism among parasites in the induced disease.

PMID- 8758141
TI  - Therapeutic effects of chloroquine in combination with quinine in uncomplicated
      falciparum malaria.
AB  - The efficacy and toxicity of oral quinine combined with oral chloroquine were
      studied in 50 Thai men with uncomplicated falciparum malaria. All were treated
      for 7 days with quinine sulphate (10 mg salt/kg every 8 h). Twenty-five of the
      patients, selected at random, were also given oral tetracycline (4 mg/kg four
      times daily) over the same period and the remainder were given chloroquine (25 mg
      base/kg over the first 3 days). There were no serious adverse effects. Overall
      fever-clearance times (FCT) and parasite-clearance times (PCT) in the chloroquine
      and tetracycline groups were not significantly different, with mean (S.D.) values
      of 51 (33) and 41 (27) h for FCT and 80 (25) and 83 (21) h for PCT, respectively.
      Most of the patients (18 in each group) were followed for > or = 2 months.
      Recrudescence rates (R1) were significantly higher in the chloroquine group than
      in the tetracycline group (39% v. 6%; P = 0.02), all recrudescences occurring
      within 4 weeks (18-25 days) of starting treatment. Subsequent parasitaemia with
      Plasmodium vivax, however, occurred less frequently in the chloroquine group
      (11%) than in the tetracycline group (33%) (P = 0.11) and took longer to develop
      in the chloroquine group [51 or 59 days compared with a mean (S.D.) value of 29
      (10) days in the tetracycline group; P = 0.01]. Within the chloroquine group, FCT
      and PCT were both shorter in those with cure than in those with R1 resistance,
      with mean (S.D.) values of 41 (25) and 70 (33) h for FCT (P = 0.09) and 72 (20)
      and 100 (18) h for PCT (P = 0.01), respectively. Chloroquine does not potentiate
      the clinical response to quinine against resistant strains of uncomplicated
      falciparum malaria, nor does it convey any useful antipyretic effect.

PMID- 8758143
TI  - Therapeutic effect of reference antileishmanial agents in murine visceral
      leishmaniasis due to Leishmania infantum.
AB  - A sensitive, culture-based, microtitration technique has recently been developed
      for determining parasite burdens in organs recovered from Balb/c mice infected
      with Leishmania infantum. In the present study, this technique was used to
      examine the efficacy of three, first-line, antileishmanial agents in reducing
      parasite burdens and eradicating parasites from target organs in mice. Treatment
      with meglumine antimoniate (50 mg SbV/kg.day) significantly reduced the parasite
      burdens in the livers and lungs (by about 10-fold and > 100-fold, respectively)
      but not those in the spleens. Although use of a higher dose of meglumine
      antimoniate (200 mg SbV/kg.day) resulted in an even more dramatic reduction in
      the parasite burdens in the livers, it had no significant effect on the burdens
      in the spleens. Treatment with amphotericin B (0.8 mg/kg every other day)
      resulted in significant reductions in the parasite burdens in the livers, spleens
      and lungs of infected mice. Although low doses of aminosidine (20 mg/kg.day) had
      no effect, high doses (200 mg/kg.day) resulted in undetectable parasite burdens
      in the livers, for at least 100 days post-treatment, and marked reductions in
      burdens in the spleens. These results are consistent with previous data from
      studies using animal models of visceral leishmaniasis. Thanks to the sensitivity
      of the technique, culture microtitration revealed that none of the drug schedules
      achieved the elimination of all parasites in all target organs. The murine model
      used mimics some important features of HIV/Leishmania infantum co-infections in
      humans.

PMID- 8758145
TI  - Fulminant, systemic strongyloidiasis in AIDS.
AB  - The 15th known case of systemic Strongyloidiasis in an AIDS patient is recorded,
      with emphasis on the fulminant clinical cause and diffuse organ involvement.

PMID- 8758144
TI  - Human behaviour, water usage and schistosomiasis transmission in a small
      settlement near Yola, Nigeria.
AB  - A study of the social, environmental and parasitological factors involved in the
      transmission of schistosomiasis among 1834 residents of a small settlement within
      an agricultural establishment near Yola, Nigeria, was carried out between June
      1991 and May 1992. Water-contact rates and the prevalences of urinary
      schistosomiasis and intestinal schistosomiasis (40.0% of all contacts, 98% and
      79%, respectively) were highest among children of 5-12 years, who were also the
      major contributors to the contamination of the Lake Geriyo environment with
      faeces and urine. The frequency and duration of water contact followed a seasonal
      pattern and seemed to be influenced by physiological and social needs such as
      defecation, urination and avoidance of harsh weather conditions. The interplay
      between a need for water contact, sanitation, freshwater snails and a supportive
      environment ensures a recycling of parasites within the studied community. This,
      in turn, helps to maintain a parasite bank from which infection is probably
      spread to other areas of the state. The present study is part of a series, on the
      dynamics of schistosomiasis transmission, which began with a study of the ecology
      of the freshwater snails in the same area.

PMID- 8758146
TI  - Human dirofilariasis in Greece: a review of reported cases and a description of a
      new, subcutaneous case.
AB  - A superficial analysis of Greek reports of human cases of dirofilariasis
      indicated that this zoonosis is rare in Greece. However, a more detailed review
      of the international literature revealed several more cases, diagnosed and
      recorded in other countries following infection during holidays in Greece.
      Overall, at least 20 individuals are now known to have been infected in Greece,
      in all regions of the country. A new, subcutaneous case of dirofilariasis is
      described; the infection occurred in a 45-year-old male living in Piraeus
      (Athens), and was localized in the abdominal wall. Histology revealed a female
      Dirofilaria (Nochtiella) repens in the reactive nodule.

PMID- 8758147
TI  - Agglutination of Leishmania promastigotes by midgut lectins from various species
      of phlebotomine sandflies.
AB  - Lectins which agglutinate Leishmania promastigotes were demonstrated in gut
      lysates from laboratory colonies of five Phlebotomus and two Lutzomyia species.
      In general, the highest agglutination titres were found in P. halepensis and Lu.
      longipalpis (Jacobina). Marked differences were found in the agglutination of
      promastigotes of various Leishmania species and strains and high agglutination
      titres were observed in some natural vector-parasite combinations, such as
      Phlebotomus argentipes and Le. donovani. Intraspecific variability, in
      agglutination of Le. major strains, could be related to the varying infectivity
      of the strains to laboratory animals. Similar carbohydrates, of which the most
      effective were D-mannosamine and N-acetyl-D-glucosamine, inhibited the
      agglutination of Le. major and Le. donovani promastigotes by midgut extracts from
      P. papatasi and Lu. longipalpis. D-Mannosamine and N-acetyl-D-glucosamine
      inhibited agglutination of promastigotes in all vector-parasite combinations. The
      results of the carbohydrate-inhibition tests indicate that the lectin
      specificities in Phlebotomus are similar to those in Lutzomyia.

PMID- 8758149
TI  - An outbreak of the vesicating beetle Paederus sabaeus Er. (Coleoptera:
      Staphylinidae) in Rivers State, Nigeria.

PMID- 8758148
TI  - Self-protection from malaria vectors in Pakistan: an evaluation of popular
      existing methods and appropriate new techniques in Afghan refugee communities.
AB  - Experimental huts were used to measure the impact of several techniques for self
      protection from malaria vectors in Pakistan. An electric fan, pyrethrum coils,
      untreated curtains, pyrethroid-vaporizing mats and permethrin-impregnated
      curtains reduced the total catches of blood-fed Anopheles stephensi by 27%, 36%,
      47%, 56% and 65%, respectively. The most marked effect of all the interventions
      was in reducing the numbers of mosquitoes entering the huts, although all the
      techniques, except for the untreated curtain, also reduced the proportion of
      mosquitoes inside the hut which fed. Although the trends seen were similar for
      both anopheline (all An. stephensi) and culicine mosquitoes, they were more
      pronounced in the culicines. Social surveys were conducted on current self
      protection practices. The social and economic constraints associated with each of
      the various techniques are discussed. All the strategies were shown to offer a
      degree of protection and their use should be encouraged. Impregnated curtains
      seem especially promising. Pyrethroid-impregnated bednets have been widely
      promoted in eastern Afghanistan since 1991 and have the advantage of providing
      protection when people sleep outside during the summer. However, surveys show
      that some owners stop using their nets in late autumn, despite the continued risk
      of malaria. People should be encouraged to use their bednets as impregnated
      curtains rather than putting them into storage.

PMID- 8758150
TI  - Infusion systems.

PMID- 8758151
TI  - Improvements in anaesthetic care resulting from a critical incident reporting
      programme.
AB  - The role of an anaesthetic incident reporting programme in improving anaesthetic
      safety was studied. The programme had been running for 4 to 5 years in three
      large hospitals in Hong Kong and more than 1000 incidents have been reported. The
      number of reports being made and frequency of the various categories of incident
      reported, did not alter during the study period. Sixty nine percent of incidents
      were considered to be preventable. Human error contributed to 76% of incidents
      and violations of standard practice to 30% of incidents. The programme was
      effective in its ability to detect latent errors in the anaesthesia system and
      when these were corrected, incidents did not recur. The frequency with which
      various contributing factors were cited did not decrease with time. With the
      exception of problems dealt with by specific protocol development, the study
      found no evidence that an increasing awareness of the problem of human error was
      effective in reducing this kind of problem.

PMID- 8758152
TI  - Sevoflurane degradation by soda lime in a circle breathing system.
AB  - Sevoflurane is degraded by soda lime to a vinyl ether commonly referred to as
      compound A. We measured the concentration of compound A in the circle breathing
      system of 31 patients receiving sevoflurane anaesthesia. Inspiratory and
      expiratory gas samples were analysed using gas chromatography and flame
      ionisation detection. The end-tidal sevoflurane concentration and soda lime
      temperature were recorded. The peak compound A concentration ranged between 10 to
      32 ppm in the inspiratory limb and 7 to 26 ppm in the expiratory limb. There was
      a positive correlation between the peak compound A concentration and the end
      tidal sevoflurane concentration (r2 = 0.545, p < 0.0001) and the soda lime
      temperature (r2 = 0.301, p = 0.0014). We conclude that the end-tidal
      concentration of sevoflurane and the temperature of the soda lime are important
      variables in determining concentration of compound A in a circle system.

PMID- 8758153
TI  - Spinal anaesthesia induced by intrathecal magnesium sulphate.
AB  - We have demonstrated in a rat model that the intrathecal injection of 0.02 ml of
      6.3% magnesium sulphate, a concentration iso-osmolar with rat plasma, will
      produce a state of spinal anaesthesia and general sedation, lasting approximately
      1 h. These effects reversed completely after 6 h, without evidence of
      neurotoxicity, immediately or during the period 1 week following the injection.
      The accompanying changes in haemodynamic and respiratory functions were minimal
      throughout the period of anaesthesia and compare favourably with those induced by
      an intrathecal bolus of 0.04 ml of 2% lignocaine.

PMID- 8758154
TI  - An investigation of the effects of heparin, low molecular weight heparin,
      protamine, and fentanyl on the balance of pro- and anti-inflammatory cytokines in
      in-vitro monocyte cultures.
AB  - We report a study conducted to determine if drugs given peri-operatively during
      cardiac surgery could themselves modulate the balance of pro- and anti
      inflammatory cytokines. We determined the cytokine response of 10 separate in
      vitro monocyte cultures to the administration of drugs at concentrations used
      during cardiac 'surgery:fentanyl (25 ng.ml-1), heparin 2.5 i.u.ml-1, heparin with
      an equal concentration of protamine, and enoxaparin 2.5 i.u.ml-1. Fentanyl,
      heparin and low molecular weight heparin (enoxaparin) led to increased tumour
      necrosis factor alpha but this did not reach statistical significance. Tumour
      necrosis factor soluble receptor 1 and 2 was not elevated. Interleukin-1 beta was
      increased by heparin (p < 0.05), whereas interleukin-1 receptor antagonist was
      increased by fentanyl (p < 0.05). Protamine blocked the heparin-induced increase
      in tumour necrosis factor alpha and interleukin-1 beta. These data raise the
      possibility that endogenous and exogenously administered opioids may be partly
      contributing to the interleukin-1 receptor antagonist response seen during major
      surgery.

PMID- 8758155
TI  - Audit in pain clinics: changing the management of low-back and nerve-damage pain.
AB  - This audit study took place in ten outpatient pain clinics and focused on the
      management of low back pain and nerve-damage pain. The objective was to identify
      and promote appropriate changes in management. An analysis of the treatment of
      1236 patients with low back pain and/or nerve-damage pain highlighted wide
      variations in practice. Presentation of these data to the clinics was used as a
      means of promoting change. Data on a further 1791 patients were used to assess
      the extent of any changes in practice. Prior to the audit feedback, treatments
      were used often in some clinics, but only rarely in other clinics, for seemingly
      similar patients. During the feedback sessions three treatments were identified
      for more frequent use by several of the clinics: antidepressant and
      anticonvulsant drugs, and transcutaneous electrical nerve stimulation. Many
      changes in practice occurred after the audit intervention, with large increases
      in the utilisation of these three treatments. Since there is reasonable evidence
      to support the use of these treatments for chronic pain this represents an
      improvement in the process of care. The audit demonstrated that patient
      management can be improved by a combination of active feedback and discussions
      based around comparisons between centres.

PMID- 8758156
TI  - Epidural morphine for postherpetic neuralgia.
AB  - Eleven patients with established postherpetic neuralgia, unresponsive to
      antidepressant therapy, entered this single-blind, placebo-controlled study to
      assess the effectiveness of epidural morphine in the control of the pain of
      postherpetic neuralgia. Two patients obtained a reduction in pain of greater than
      50% following morphine 0.5 mg. The duration of this pain relief was 36 h in one
      patient and 72 h in the other. Repeated doses, however, were ineffective in one
      patient and resulted in intolerable side effects in the other. The other six
      patients who received morphine developed opioid-related side effects without pain
      relief. Three patients did not receive morphine as they gained significant, long
      lasting pain relief from placebo. Two retained that benefit for more than 6
      months. Epidural morphine is more likely to produce side effects than pain relief
      when administered to patients with postherpetic neuralgia.

PMID- 8758157
TI  - Effect of bupivacaine-induced spinal block on the hypnotic requirement of
      propofol.
AB  - The hypnotic dose-response of propofol was compared with its combination with
      either bupivacaine-induced spinal block or intramuscular bupivacaine 12.5 mg in
      105 men, divided into three groups of 35, undergoing lower abdominal, pelvic or
      lower limb surgery. Dose-response curves were determined for each group using
      bootstrap analysis. Bupivacaine-induced spinal block at the level of T8-T9 was
      found to reduce the ED50 of propofol by 39%. While this enhancement of hypnotic
      effect by spinal block is mostly attributable to reduced afferent input,
      differences in its potency between drugs suggest a role for additional factors.

PMID- 8758158
TI  - The use of a non-invasive method to measure intrapulmonary shunt during one-lung
      anaesthesia.
AB  - The Non Invasive Virtual Shunt computer program has previously been described and
      validated. The system has subsequently been developed to give a real time,
      continuous trace of virtual shunt. A portable computer connected to routine
      monitoring equipment displays a plot of virtual shunt updated every 10 s. A
      practical use of this device in the clinical setting of one-lung anaesthesia is
      described. The equipment was used to monitor shunt before, during and after
      surgery in three patients. In one case, a displaced double lumen bronchial tube
      was detected before there was any other indication of the problem.

PMID- 8758159
TI  - Systemic piroxicam as an adjunct to patient-controlled analgesia with alfentanil
      for postoperative pain relief.
AB  - In a double-blind, placebo-controlled study, the non-steroidal anti-inflammatory
      drug, piroxicam, in combination with alfentanil given in a patient-controlled
      analgesia system, was compared with alfentanil alone given by the same route for
      analgesic effect, side effects and acute phase reaction over a 4-day period
      following anterior cruciate ligament reconstruction of the knee. The patients
      receiving piroxicam had lower pain scores and consumed less alfentanil. There
      were no differences with regard to side effects between the two treatment groups,
      apart from significantly more sedation at 08.00 h on the first postoperative day
      in the non-piroxicam group. Piroxicam did not influence either the levels of
      interleukin-6 or the acute phase response to surgery.

PMID- 8758160
TI  - Spontaneous movement after injection of propofol.
AB  - Spontaneous movement following injection of propofol at induction was studied in
      303 patients. Two hundred patients were Caucasians and 103 were Asians. In a
      pilot study carried out prior to the main study, 26% of the Asians moved at
      induction as compared with 6% of the Caucasians. The patients were studied in
      relation to a number of variables; age, sex, weight, height, race, smoker/non
      smoker, vegetarian/non vegetarian, alcohol consumption, premedication, use of
      fentanyl at induction and dose of propofol. When race was included as the sole
      variable there was a marginal but not significant difference between the two
      groups in terms of movement (p = 0.06). However, when the other recorded
      variables were taken into account, race was not included as a predictor of
      whether or not the patient moved. The best model for predicting whether the
      patients moved or not combines the variables weight and dose of propofol.
      Patients were more likely to move if they were lighter and the dose of propofol
      used at induction was higher.

PMID- 8758161
TI  - A study of the brightness of laryngoscope light.
AB  - We have measured the brightness (luminance) of the light spot produced by 105
      Macintosh 3 laryngoscope blades (33 bulb, 72 fibrelight) using a Hagner
      photometer. An estimate of the minimum luminance required for laryngoscopy
      (circa. 100 cd.m-2), was determined using a laryngoscope adapted to provide a
      variable light output. Five (15%) of bulb blades and 24 (33%) of the fibrelight
      blades failed to meet this minimum level. A new bulb blade produced brighter
      lighting conditions (maximum 700 cd.m-2) than a new fibrelight blade (max. 500
      cd.m-2). In total, 61 (84%) of the fibrelight blades and three (9%) of the bulb
      blades were found to provide a light spot that encompassed areas of luminance
      below 30 cd.m-2, which is a level for comfortable reading. The light spot from a
      mains-powered fibreoptic bronchoscope was found to be four times brighter (2000
      cd.m-2) than a new battery-powered fibrelight laryngoscope.

PMID- 8758162
TI  - Optimal shape of the laryngeal mask cuff: the influence of three deflation
      techniques.
AB  - A randomised, single-blinded, controlled trial was conducted to determine if a
      new laryngeal mask deflation tool offered any advantages over manual or free
      deflation. Ten laryngeal mask airways were tested and the deflation tool provided
      a significantly superior and more consistent shape than either hand manipulation
      or the free deflation, but did not offer any benefits in terms of residual
      volume. The deflator tool should encourage wider use of the standard recommended
      insertion technique. It can be used as a backup when manual deflation cannot
      provide the correct shape and may be useful for researchers studying laryngeal
      mask airway placement.

PMID- 8758163
TI  - Anaesthesia and the Internet.
AB  - The Internet is a network of computers that allows rapid transfer of information
      throughout the world. The number of medical, and particularly anaesthetic,
      resources is rapidly increasing. This article briefly describes the Internet and
      its features which may be of interest to anaesthetists and intensivists in the
      United Kingdom, together with some of the tools for working with them.

PMID- 8758164
TI  - Hydrogen peroxide: an unusual cause of arterial and venous gas embolism.
AB  - A patient undergoing minor orthopaedic surgery suffered from unexpected arterial
      and venous gas embolism caused by hydrogen peroxide. We describe our management
      of the case and emphasise the need for continued vigilance during the use of
      hydrogen peroxide.

PMID- 8758165
TI  - Contralateral pneumothorax following thoracotomy for vertebrectomy.
AB  - A 21-year-old woman underwent correction of congenital thoracic kyphoscoliosis.
      The procedure was completed in two stages. The first stage involved right
      thoracotomy and anterior vertebrectomy. Following positional obstruction of her
      right-sided chest drain she developed a very large, left-sided pneumothorax in
      the immediate postoperative period. No attempt at central venous line placement
      had been made on the left side. Breach of the midline at vertebrectomy may allow
      pleural gas to cross and cause a contralateral pneumothorax.

PMID- 8758166
TI  - Iatrogenic vertebrojugular arteriovenous fistula.
AB  - Arteriovenous fistulae originating from the vertebral artery are rare. We report
      a patient in whom a vertebral artery-jugular venous fistula developed following
      insertion of a central venous catheter via the internal jugular vein. The fistula
      was successfully occluded surgically.

PMID- 8758167
TI  - Upper airway obstruction caused by acquired inhibitor to factor VIII.
AB  - Bleeding caused by inhibitors to factor VIII is a rare medical emergency
      requiring immediate specialist investigation and management. Urgent initiation of
      therapy with high dose factor VIII concentrates may be life saving. Successful
      management of acute upper airway obstruction from uncontrolled haemorrhage into
      the oropharyngeal tissues should be achieved with fibreoptic guided nasotracheal
      intubation.

PMID- 8758168
TI  - Compartment syndrome with severe rhabdomyolysis in the postoperative period
      following major vascular surgery.
AB  - We report a case of compartment syndrome with marked rhabdomyolysis in the
      immediate postoperative period following major vascular surgery. Early and
      aggressive treatment, based on intravenous fluids, sodium bicarbonate, mannitol
      and fasciotomy, resulted in satisfactory management of the patient and prevented
      the onset of severe complications, such as acute renal failure in a patient who
      presented several factors that predisposed him to this disorder.

PMID- 8758169
TI  - A comparison of epidural infusions of fentanyl or pethidine with bupivacaine in
      the management of postoperative pain.
AB  - A double-blind randomised clinical trial was undertaken in 40 patients undergoing
      major abdominal surgery. Postoperative pain relief was provided using epidural
      infusions of 0.06% bupivacaine with fentanyl 4 micrograms.ml-1 (n = 20) (group F)
      or with pethidine 1.5 mg.ml-1 (n = 20) (group P). Postoperative pain scores using
      a visual analogue scale (0-100 mm) were not significantly different between the
      two groups. Median pain scores were 0-19 mm at all times of assessment indicating
      that good analgesia was provided by both regimens. There was no significant
      difference between the epidural infusion rates in the two groups. The side
      effects and effect on pulmonary function were similar in each group. Nine
      patients were withdrawn from the study (four from group F, five from group P) due
      to failure of the epidural technique or other complications. Fourteen patients,
      equally distributed, required a total of 24 epidural 'top-ups' by an anaesthetist
      because of inadequate analgesia. We demonstrated no advantage with epidural
      pethidine over fentanyl when used by infusion in combination with bupivacaine in
      the management of postoperative pain.

PMID- 8758170
TI  - Topical lignocaine and thiopentone for the insertion of a laryngeal mask airway;
      a comparison with propofol.
AB  - We assessed conditions for insertion of a laryngeal mask airway in 90
      unpremedicated adult patients who received either thiopentone 5 mg.kg-1 preceded
      by 40 mg of topical lignocaine spray to the posterior pharyngeal wall or propofol
      2.5 mg.kg-1 alone in a randomised, single-blinded trial. All patients received
      fentanyl 1 microgram.kg-1. Gagging, coughing and laryngospasm following laryngeal
      mask insertion were graded and haemodynamic data and apnoea times were recorded.
      There were no significant differences between the two groups with regard to the
      incidence of gagging, coughing and laryngospasm, but the apnoea time was
      significantly less in the thiopentone group (p < 0.005). The decrease in systolic
      and diastolic blood pressure, following induction and the insertion of a
      laryngeal mask with propofol was significantly greater than following thiopentone
      (p < 0.05--systolic, p < 0.01--diastolic). We conclude that thiopentone preceded
      by topical lignocaine spray provides conditions for insertion of a laryngeal mask
      equal to those of propofol, with more haemodynamic stability and a shorter period
      of apnoea.

PMID- 8758171
TI  - Oxygen saturation of patients recovering from electroconvulsive therapy.
AB  - Oxygen saturation was measured by pulse oximetry in 33 psychiatric patients
      breathing air during recovery from 60 episodes of electroconvulsive therapy.
      Desaturation to less than 90% occurred in 17% of patients. Oxygen saturation
      values in recovery were significantly lower than pre-operative saturations (p =
      0.0014 using ANOVA), with a significant difference (p = 0.001) for up to 5 min in
      recovery.

PMID- 8758172
TI  - A lesson in the management of anaphylactic reactions.

PMID- 8758173
TI  - Patient controlled co-sedation.

PMID- 8758174
TI  - Laryngeal mask airway and lingual nerve injury.

PMID- 8758175
TI  - Recurrent laryngeal nerve palsy and the laryngeal mask airway.

PMID- 8758176
TI  - Subdural or epidural?

PMID- 8758177
TI  - The use of obstetric emergency drug trays: room for improvement?

PMID- 8758178
TI  - Near infrared spectroscopy.

PMID- 8758179
TI  - Gastric intramucosal pH.

PMID- 8758180
TI  - Complications of intrathecal administration of pethidine.

PMID- 8758181
TI  - Transtracheal ventilation.

PMID- 8758182
TI  - Anaesthesia for exodontia in young children--a snapshot survey of European
      practice.

PMID- 8758183
TI  - Knotted guidewire--A complication of Hickman line insertion.

PMID- 8758184
TI  - A new method of chest drain insertion.

PMID- 8758185
TI  - What do patients want from medical research?

PMID- 8758186
TI  - Can acupuncture have specific effects on health? A systematic review of
      acupuncture antiemesis trials.
AB  - The effects of acupuncture on health are generally hard to assess. Stimulation of
      the P6 acupuncture point is used to obtain an antiemetic effect and this provides
      an excellent model to study the efficacy of acupuncture. Thirty-three controlled
      trials have been published worldwide in which the P6 acupuncture point was
      stimulated for treatment of nausea and/or vomiting associated with chemotherapy,
      pregnancy, or surgery. P6 acupuncture was equal or inferior to control in all
      four trials in which it was administered under anaesthesia; in 27 of the
      remaining 29 trials acupuncture was statistically superior. A second analysis was
      restricted to 12 high-quality randomized placebo-controlled trials in which P6
      acupuncture point stimulation was not administered under anaesthesia. Eleven of
      these trials, involving nearly 2000 patients, showed an effect of P6. The
      reviewed papers showed consistent results across different investigators,
      different groups of patients, and different forms of acupuncture point
      stimulation. Except when administered under anaesthesia, P6 acupuncture point
      stimulation seems to be an effective antiemetic technique. Researchers are faced
      with a choice between deciding that acupuncture does have specific effects, and
      changing from 'Does acupuncture work?' to a set of more practical questions; or
      deciding that the evidence on P6 antiemesis does not provide sufficient proof,
      and specifying what would constitute acceptable evidence.

PMID- 8758187
TI  - The chemokines: cytokines that direct leukocyte migration.

PMID- 8758189
TI  - The euthanasia debate: in reply to Lord Walton.

PMID- 8758188
TI  - Psoriasis, T cells and autoimmunity.

PMID- 8758190
TI  - An analysis of telephone calls to an inner-city accident and emergency
      department.
AB  - The general public in the UK often telephone accident and emergency (A&E)
      departments for medical advice. Such calls are usually dealt with by nursing
      staff in an informal manner (often with no written record of the call being
      made). The specific questions addressed in this study are who was calling for
      advice, when did they call, what were their presenting complaints, and what was
      the outcome of the call? In addition, the study provided an opportunity to test
      the implementation of a new system of record-keeping for telephone consultation.
      A telephone consultation record (TCR) was developed and used to record details of
      each call made to the A&E department for medical/health advice. An analysis of
      597 consecutive documented calls is presented in this paper. The majority of
      calls were dealt with by 'E' grade nursing staff (42.7%); only four calls (0.7%)
      were recorded by medical staff. Two hundred and six (43.5%) calls related to
      patients aged up to 15 years. In 57% of the cases the call was made by a third
      party. In all, 149 different presenting complaints were recorded on the TCRs. The
      three most common presenting complaints were dental problems (7.4%), fever
      (4.3%), and concerns about drug reactions (23%). Seventy-three per cent of
      callers were advised that a visit to the A&E department was not immediately
      necessary. The study identifies several important issues for development of a
      more formal and effective system of telephone advice. The majority of calls made
      to the A&E department appeared to be of a primary care nature but the extent to
      which nurses are trained to assess and advise on these problems needs to be
      questioned. A reluctance to document the calls to A&E was identified, one reason
      being a concern about accountability. Training and support are clearly required.

PMID- 8758191
TI  - A study in white: Dr. Watson in the medical press.

PMID- 8758192
TI  - Floaters after cataract surgery.

PMID- 8758193
TI  - High dose chemotherapy for breast cancer: the case for trials in adjuvant
      therapy.
AB  - Adjuvant polychemotherapy reduces the annual mortality for breast cancer, the
      effect being seen for at least the first decade after primary treatment for stage
      II disease. However, the overall benefit is modest with an annual reduction in
      the odds of death of the order of 20%-30%. For patients at standard or low risk
      of recurrence this appears to be an acceptable benefit given low toxicity of
      treatment. However, some patients have a very much worse prognosis identifiable
      on the basis of the number of involved axillary nodes at surgery. Patients with
      more than 10 lymph nodes, for example, have a predicted survival of less than 30%
      at 5 years and around 10% at 10 years. High dose chemotherapy has shown immediate
      benefits in terms of complete response rates in advanced breast cancer. Potential
      benefits of this treatment could be even higher in the adjuvant setting given the
      patient's fitness and the fact that micrometastatic disease represents the best
      clinical analogue of the successful laboratory experimental conditions. Now that
      the safety factors appear to be favourable with a treatment-related mortality of
      less than 5% it would appear that stage II poor risk disease is an appropriate
      setting to test high dose chemotherapy against the best conventional therapy in
      randomized trials.

PMID- 8758194
TI  - Mason type II radial head fractures fixed with Herbert bone screws.
AB  - The management of radial head fractures remains controversial. Accurate
      classification of the fracture (Mason) may necessitate the use of special X-ray
      views (45 degrees arterior oblique or radio-capitellar). We present the results
      of 19 cases of Mason type II fractures treated operatively by open reduction and
      internal fixation with the Herbert bone screw. All patients achieved 'good-to
      excellent' outcome at follow-up. Our results compare favourably with other forms
      of treatment for this injury.

PMID- 8758195
TI  - Cochlear implants in children: principles, practice and predictions.
AB  - An audit was undertaken of the first 36 children who had received cochlear
      implants in Nottingham. These children had previously derived no benefit from
      prolonged trials of powerful hearing aids. Following implantation, all children
      could hear warble tones at all audiometric frequencies from 500 to 4000 Hz at
      sound pressure levels between 30 and 50 dB. The majority of children implanted
      below the age of 5 years developed intelligible spoken language after 3 years.
      The outcomes for children born deaf and those who acquired deafness under the age
      of 3 years were substantially similar. The best results were obtained in those
      children who were implanted before the age of 5 years or in whom the deafness was
      of short duration. The needs of implanted children continue over many years. A
      small number of dedicated, well-funded multidisciplinary teams are needed to meet
      the growing demand nationally.

PMID- 8758196
TI  - Ilizarov bone transport for the treatment of chronic osteomyelitis: a rare
      complication.

PMID- 8758197
TI  - Brain electrical activity mapping (BEAM): a diagnostic technique for heat-induced
      cerebral dysrhythmia?

PMID- 8758198
TI  - Ornamental fish: look but do not touch!

PMID- 8758199
TI  - Women doctors--a review.

PMID- 8758200
TI  - Acute mountain sickness.

PMID- 8758201
TI  - Major vascular injury during lumbar laminectomy.

PMID- 8758202
TI  - Evidence-based pathology.

PMID- 8758203
TI  - Helicobacter pylori infection and gastric cancer.

PMID- 8758204
TI  - How to differentiate between T-cell-rich B-cell lymphoma and lymphocyte
      predominant Hodgkin's disease. Evidence for the value of MB1 and 4KB5
      immunostaining.
AB  - Striking morphological similarities exist between T-cell-rich B-cell lymphoma and
      lymphocyte-predominant Hodgkin's disease (Hodgkin's paragranuloma), making the
      distinction between them extremely difficult. Immunohistochemistry provides a
      means of overcoming this difficulty. Immunostaining with UCHL1, L26, MB1, and
      4KB5 was performed on five T-cell-rich B-cell lymphomas and 11 Hodgkin's
      paragranulomas (7/11 nodular, 4/11 diffuse). L26 stained the tumour cells not
      only of T-cell-rich B-cell lymphomas, but also of L+H Hodgkin's disease. In
      contrast, MB1 as well as 4KB5 identified all of the neoplastic cells in 3/5 T
      cell-rich B-cell lymphomas, but did not react with the L+H cells in 8/11
      Hodgkin's paragranulomas. Some overlap of staining patterns became apparent in
      the remaining cases, with 2/5 T-cell-rich B-cell lymphomas showing the MB1+/4KB5+
      phenotype in a tumor cell subset only. Similarly, in 3/11 Hodgkin's
      paragranulomas, some MB1/4KB5-positive L+H cells occurred in addition to MB1/4KB5
      negative L+H cells. These cases, nevertheless, could be distinguished from one
      another by the numbers of MB1/4KB5-positive background lymphocytes, which were
      scanty or absent in T-cell-rich B-cell lymphomas and more numerous in Hodgkin's
      paragranulomas.

PMID- 8758205
TI  - BCL-6 expression in reactive lymphoid tissue and in B-cell non-Hodgkin's
      lymphomas.
AB  - Chromosomal abnormalities involving 3q27 have recently been associated with
      diffuse large B-cell lymphomas and, less frequently, with follicular lymphomas.
      Molecular studies have led to the identification of the BCL-6/LAZ-3 gene, located
      at 3q27 and coding for a putative zinc-finger protein that might act as a
      transcriptional regulator during cell differentiation and development.
      Rearrangement of BCL-6 results in truncation of the gene in its 5' portion,
      leaving the protein intact; a resultant deregulation of its expression has been
      hypothesized. In order to test this hypothesis, the expression of BCL-6 protein
      was investigated in human reactive lymphoid tissue and compared with a group of
      non-Hodgkin's lymphomas (NHLs) with or without 3q27 anomalies and/or BCL-6 gene
      rearrangement. BCL-6 protein is consistently expressed in reactive lymphoid
      tissues, where it is restricted to the follicle centre. The protein is also
      widely expressed in NHL: all follicular lymphomas tested showed a pattern of
      expression similar to the reactive B follicle, independently of the presence of
      BCL-6 gene rearrangement and/or 3q27 anomalies. In the diffuse large B-cell
      lymphomas, there was more variation in BCL-6 expression, but a correlation with
      3q27 anomalies and/or BCL-6 rearrangement was not found. Deregulation of the BCL
      6 gene did not result in an aberrant tissue expression as detected by
      immunohistochemistry.

PMID- 8758206
TI  - Mutation of the Von Hippel-Lindau tumour suppressor gene in capillary
      haemangioblastomas of the central nervous system.
AB  - A series of 20 capillary haemangioblastomas of the central nervous system was
      screened for mutations of the von Hippel-Lindau (VHL) tumour suppressor gene by
      single strand conformational polymorphism (SSCP) and heteroduplex analysis.
      Aberrant polymerase chain reaction (PCR) products were detected in ten tumours.
      DNA sequencing of these PCR products revealed that seven tumours had frameshift
      mutations due either to deletions of one or more base pairs (six cases) or to
      insertion of one base pair (one case). The remaining three tumours had either
      point mutations of intron splice site sequences (two cases) or a point mutation
      resulting in an amino acid substitution (one case). Evidence for germline
      alterations of the VHL gene was found in two patients who showed identical
      mutations in both tumour and corresponding leukocyte DNA. The results suggest
      that mutation of the VHL tumour suppressor gene represents a significant event in
      the development of capillary haemangioblastomas.

PMID- 8758207
TI  - Mutation of the VHL gene is associated exclusively with the development of non
      papillary renal cell carcinomas.
AB  - To define the possible role of the VHL gene in the development of sporadic renal
      cell carcinomas, 91 different parenchymal tumours of the kidney have been
      investigated for mutation of the VHL gene by single strand conformation
      polymorphism (SSCP) and/or heteroduplex (HD) techniques. Chromosome 3p deletion
      was detected in 98 per cent of non-papillary renal cell carcinomas and in 25 per
      cent of chromophobe renal cell carcinomas. In 22 of the 43 non-papillary renal
      cell carcinomas, abnormally migrating DNA bands were detected by SSCP and/or HD
      analysis. No mobility shift was seen in any of the 23 chromophobe renal cell
      carcinomas. In addition, 15 papillary renal cell tumours and ten renal
      oncocytomas, which are characterized by genetic changes other than loss of
      chromosome 3p sequences, were analysed for mutation of the VHL gene. None of
      these tumours showed abnormal migration patterns. The results indicate that
      mutation of the VHL gene is associated exclusively with the development of non
      papillary renal cell carcinoma.

PMID- 8758208
TI  - The expression pattern of Wilms' tumour gene (WT1) product in normal tissues and
      paediatric renal tumours.
AB  - WT1, the Wilms' tumour suppressor gene located at chromosome 11p13, plays an
      important role in the development of the kidney. It is mutated in 10 per cent of
      Wilms' tumours (WTs) and their putative precursors called nephrogenic rests
      (NRs). A sensitive immunohistochemical technique was established to localize the
      WT1 gene product in archival normal tissues and paediatric renal tumour samples.
      Strong nuclear signal was seen in the various sites such as the kidneys, gonads,
      and decidua. Nuclear immunoreactivity of variable intensity was also seen in the
      skeletal muscle, smooth muscle of urinary bladder, ureter, and arteries. All 28
      WTs (including the anaplastic variant) showed the WT1 gene product in a varying
      proportion of the blastema, epithelium, and stroma. The anaplastic nuclei in six
      WTs showed an intensity of staining comparable to their adjacent favourable
      histology counterparts. All the intralobar and perilobar types of NR demonstrated
      the WT1 gene product. All three malignant rhabdoid tumours were positive, while
      three of four mesoblastic nephromas and a clear cell sarcoma were negative. These
      findings provide an insight into the interrelationships of these renal tumours.

PMID- 8758209
TI  - Loss of chromosome 9 in tissue sections of transitional cell carcinomas as
      detected by interphase cytogenetics. A comparison with RFLP analysis.
AB  - Interphase cytogenetics by in situ hybridization (ISH) using a panel of
      centromere-associated DNA probes for chromosomes 1, 7, 9, 10, 11, 16, 17, and 18
      was performed on 5 microns thick frozen tissue sections of transitional cell
      carcinomas (TCCs) of the urinary bladder. By this approach, chromosome ploidy,
      numerical chromosome aberrations, imbalance between chromosomes, and
      heterogeneity of aberrations within individual tumours were determined. In 15 of
      24 TCCs, loss or underrepresentation of chromosome 9, compared with the ISH copy
      numbers of at least five other chromosomes, was demonstrated. Independently, RFLP
      analysis were performed on the same cases to detect loss of heterozygosity (LOH)
      of chromosome loci 9q34, 11p15, 16q22-24, 17p13, and 18q21. LOH was found in 9 of
      19 informative cases for chromosome locus 9q34. Comparison of the ISH and RFLP
      results showed no correlation between numerical aberration and LOH for the loci
      on chromosomes 11, 16, 17, and 18. However, numerical loss of chromosome 9 was
      found in 89 per cent (eight of nine cases) with LOH for 9q34. Conversely, LOH at
      9q34 was observed in only 67 per cent (eight of 12 cases) with
      underrepresentation of chromosome 9. Moreover, in 60 per cent of the non
      informative cases (three of five cases), underrepresentation for chromosome 9 was
      observed. These results indicate that the heterochromatin probe for chromosome 9
      can be reliably used in TCC tissue sections for the detection of chromosomal
      loss. In aneuploid TCCs, this DNA probe can be used for the detection of
      chromosomal underrepresentation only in combination with other centromere
      associated DNA probes.

PMID- 8758210
TI  - p53 mutation, allele loss on chromosome 17p, and DNA content in ovarian
      carcinoma.
AB  - The aim of this investigation was to explore the relationships between p53
      mutation, DNA aneuploidy, 17p deletions, and clinical stage in ovarian cancer.
      Nuclear suspensions were obtained by tissue disaggregation, stained with
      propidium iodide, and analysed on a Coulter EPICS Elite flow cytometer. DNA cell
      cycle analysis was performed using Multicycle software (Phoenix Flow Systems).
      DNA extracted from paraffin-embedded archival carcinomas/non-tumour tissue was
      used as template for PCR amplification of the microsatellite dinucleotide repeat
      polymorphism D17S513, a locus telomeric to p53 on 17p13.1. Allele loss at D17S513
      was detected in 64.5 per cent of carcinomas (20 of 31 informative cases). DNA
      aneuploidy was detected in 20 of 54 (37 per cent) carcinomas. Eight of ten cases
      previously shown to harbour p53 mutations showed aneuploid DNA content. Although
      ten other DNA aneuploid cases had shown no p53 mutations, the results show a
      statistically significant association between p53 mutation and DNA aneuploidy (P
      < 0.01). Furthermore, the mean DNA index of the DNA aneuploid cases was
      significantly higher in p53 mutant cases compared with those showing no p53
      mutation (P = 0.02). There was also a significant association between p53
      mutations and stage, between ploidy and stage, and between allelic deletions at
      D17S513 or p53 and stage, but not between these allelic deletions and ploidy. p53
      mutations appear to be associated with DNA aneuploidy in ovarian cancer
      independently of 17p deletions. p53 mutations, DNA aneuploidy, and 17p deletions
      are associated with late stage.

PMID- 8758211
TI  - Cadherin expression in melanocytic naevi and malignant melanomas.
AB  - An immunocytochemical study has been undertaken of cadherin expression in 11
      benign melanocytic naevi and 14 malignant melanomas. Anti-pan-cadherin rabbit
      antibodies, which recognize multiple cadherin subtypes, demonstrated cadherin
      expression of moderate or strong intensity in 8 of 11 naevi. Expression was
      restricted to the more superficial melanocytes which possessed abundant cytoplasm
      (type A melanocytes). More deeply located melanocytes possessing little cytoplasm
      (type B melanocytes) or having a spindle cell morphology (type C melanocytes)
      lacked detectable pan-cadherin expression. The monoclonal antibody HECD-1
      detected weak E-cadherin immunostaining in all 11 naevi, expression again being
      limited, with a single exception, to type A melanocytes. Cadherin immunostaining
      of moderate or strong intensity was detected by the pan-cadherin antibody in all
      14 malignant melanomas. In contrast to naevi, cadherin expression in melanomas
      frequently extended into the deepest portions of the tumours. E-cadherin
      immunostaining in malignant melanomas was generally much stronger than that seen
      in naevi, often being of comparable intensity to the pan-cadherin staining. In
      summary, cadherins are frequently expressed in melanocytic tumours. In naevi,
      cadherin expression is related to the degree of melanocytic maturation. Cadherin
      expression, and particularly E-cadherin expression, tends to be greater in
      malignant melanomas than in naevi.

PMID- 8758212
TI  - Collagen distribution in focal and segmental glomerulosclerosis: an
      immunofluorescence and ultrastructural immunogold study.
AB  - Focal and segmental glomerulosclerosis (FSGS) is a non-specific scarring process
      of the glomerulus, initially described in idiopathic nephrotic syndrome. The
      distribution of types I, III, IV, V, and VI collagen and of the alpha 1, alpha 3,
      alpha 4, alpha 5, and alpha 6 chains of type IV collagen was studied by
      immunohistochemistry in sclerotic lesions of nine nephrotic children. Dual
      immunofluorescence and high-resolution immunogold labelling were used to
      determine the precise distribution of the antigens. No changes were detected in
      normal glomeruli of patients compared with controls. In FSGS, type IV collagen
      [alpha 1(IV)2 alpha 2(IV)], and to a lesser degree type VI, accumulates in the
      two components of the lesion: the enlarged mesangial matrix and the material
      deposited between the pushed-out podocytes and the alpha 3-alpha 5(IV)-positive
      glomerular basement membrane. Staining for alpha 6(IV) and types I, III, and V
      collagen was practically negative. These results suggest that the matrix
      components of the sclerotic lesion are produced solely by glomerular cells.
      Changes in the relative distribution of type IV collagen chains, characterized by
      the presence of collagen [alpha 1(IV)2 alpha 2(IV)] in close contact with the
      podocytes, strongly suggest a switch in the podocyte programme of collagen
      synthesis.

PMID- 8758213
TI  - Explanted vein grafts with an intact endothelium demonstrate reduced focal
      expression of endothelial nitric oxide synthase specific to atherosclerotic
      sites.
AB  - The endothelial L-arginine:nitric oxide (NO) system is fundamental to vascular
      function. It is becoming evident that this system is compromised in aorto
      coronary vein grafts, although it is not clear how it is affected. It was
      postulated that the development of intimal lesions in vein grafts may be
      associated with reduced expression or loss of endothelial NO synthase (eNOS). The
      immunocytochemical localization and quantitative expression of eNOS were
      therefore investigated in normal human saphenous veins (n = 6) and explanted vein
      grafts (n = 6). The vein grafts demonstrated marked morphological changes evident
      as fibro-intimal hyperplasia (FIH) and focal sites of atherosclerosis, often
      occurring along the same length of graft. Staining for eNOS was abundantly
      evident in the endothelium of normal veins but revealed a differential reduction
      in staining intensity in vein grafts. Staining intensity measurements revealed a
      significant reduction (P < 0.001) in the amount of eNOS present in areas of
      atherosclerosis as compared with normal veins and areas of vein graft with FIH
      changes alone. This reduction in the relative quantity of antigen was specific to
      eNOS, since the endothelial markers von Willebrand factor (vWf) and CD31 showed
      no such variations. These data support the view that vascular activity of NO is
      impaired in atherosclerosis and indicate that reduced expression of eNOS, and
      therefore by inference lower NO production, may make an important contribution to
      this phenomenon.

PMID- 8758214
TI  - Microvascular angiopathy in advanced periodontal disease.
AB  - Previous studies have shown a perivascular hyaline thickening affecting
      restricted regions of the microcirculation in gingivitis and moderate
      periodontitis and in the pulpal vessels in chronic pulpitis. In the present study
      of the lesion of advanced periodontitis, immunostaining for type IV collagen and
      laminin demonstrated widespread deposition of basement membrane material, with
      manifest involvement of the venous network. Some vessels were associated with an
      increased deposition of both basement membrane proteins, while others showed
      preferential deposition of either laminin or type IV collagen. Immunostaining
      also revealed an extensive trabecular network of type IV collagen throughout the
      affected gingival tissue that was related to recognizable vessels but was co
      extensive with less intense staining for laminin. This network was not associated
      with viable endothelial cells demonstrable by staining with the endothelial
      marker Ulex agglutinin (UEA-1). The results indicate extensive vascular pathology
      in advanced periodontitis that could explain the attenuation of the inflammatory
      reaction and the restricted ability to develop reparative granulation tissue in
      this disease.

PMID- 8758215
TI  - How important is tumour shape? Quantification of the epithelial-connective tissue
      interface in oral lesions using local connected fractal dimension analysis.
AB  - Quantification of the local complexity of the epithelial-connective tissue
      interface (ECTI) in normal mucosa, epithelial dysplasia, and squamous cell
      carcinoma of the floor of the mouth was investigated by estimating the local
      connected fractal dimension in tissue profiles from histological sections. The
      use of certain parameters of the distribution of the local connected fractal
      dimensions of the ECTI classifies the cases belonging to these three
      histopathological diagnoses with 85 per cent accuracy by means of linear
      discriminant analysis. The values of the local fractal dimension were also used
      to produce colour-coded dimensional images of the ECTI, to highlight locations
      with higher irregularity that may correlate with locally invasive 'higher-risk'
      areas.

PMID- 8758216
TI  - Standardized AgNOR quantitation.

PMID- 8758217
TI  - Methodological issues in studies of air pollution and daily counts of deaths or
      hospital admissions.
AB  - STUDY OBJECTIVE: To review the issues and methodologies in epidemiologic time
      series studies of daily counts of mortality and hospital admissions and
      illustrate some of the methodologies. DESIGN: This is a review paper with an
      example drawn from hospital admissions of the elderly in Cleveland, Ohio, USA.
      MAIN RESULTS: The central issue is control for seasonality. Both over and under
      control are possible, and the use of diagnostics, including plots, is necessary.
      Weather dependence is probably non-linear, and adequate methods are necessary to
      adjust for this. In Cleveland, the use of categorical variables for weather and
      sinusoidal terms for filtering season are illustrated. After control for season,
      weather, and day of the week effects, hospital admission of persons aged 65 and
      older in Cleveland for respiratory illness was associated with ozone (RR = 1.09,
      95% CI 1.02, 1.16) and particulates (PM10 (RR = 1.12, 95% CI 1.01, 1.24), and
      marginally associated with sulphur dioxide (SO2) (RR = 1.03, 95% CI = 0.99,
      1.06). All of the relative risks are for a 100 micrograms/m3 increase in the
      pollutant. CONCLUSIONS: Several adequate methods exist to control for weather and
      seasonality while examining the associations between air pollution and daily
      counts of mortality and morbidity. In each case, care and judgement are required.

PMID- 8758219
TI  - The association between air pollution and the daily number of deaths: findings
      from the Slovak Republic contribution to the APHEA project.
AB  - STUDY OBJECTIVE: To analyse the short term relation between daily air pollutant
      values and the daily number of deaths in Bratislava, Slovak Republic, during the
      study period 1987-91. DESIGN: This follows the APHEA protocol. The association
      between the daily number of total and cause specific deaths and daily variations
      in ambient air levels of sulphur dioxide (SO2) and total suspended particulates
      (TSP) were analysed using Poisson regression that allowed control for
      meterological data and variables that handle temporal and autoregressive
      patterns. SETTING: Bratislava is the capital town of Slovakia, the total
      population was 442,999 according to 1991 census data. The dominant sources of
      industrial air pollution are the chemical industry and oil refinery. MAIN RESULTS
      AND CONCLUSIONS: After adjustment for season, temperature and relative humidity,
      days of week and holidays, secular trends, and autoregressive patterns no
      significant associations were found between the daily variations in the air
      pollutants, SO2-24 h and TSP-24 h, and total mortality (RR 0.978, 95% CI 0.96,
      0.99; RR 1.008, 95% CI 0.96, 0.99) and cause specific mortality in Bratislava
      during the study period.

PMID- 8758218
TI  - Short term effects of air pollution on health: a European approach using
      epidemiologic time series data: the APHEA protocol.
AB  - BACKGROUND AND OBJECTIVES: Results from several studies over the past five years
      have shown that the current levels of pollutants in Europe and North America have
      adverse short term effects on health. The APHEA project aims to quantifying these
      in Europe, using standardised methodology. The project protocol and analytical
      methodology are presented here. DESIGN: Daily time series data were gathered for
      several air pollutants (sulphur dioxide; particulate matter, measured as total
      particles or as the particle fraction with an aerodynamic diameter smaller than a
      certain cut off, or as black smoke; nitrogen dioxide; and ozone) and health
      outcomes (the total and cause specific number of deaths and emergency hospital
      admissions). The data included fulfilled the quality criteria set by the APHEA
      protocol. SETTING: Fifteen European cities from 10 different countries with a
      total population over 25 million. METHODOLOGY: The APHEA collaborative group
      decided on a specific methodological procedure to control for confounding effects
      and evaluate the hypothesis. At the same time there was sufficient flexibility to
      allow local characteristics to be taken into account. The procedure included
      modelling of all potential confounding factors (that is, seasonal and long term
      patterns, meteorological factors, day of the week, holidays, and other unusual
      events), choosing the "best" air pollution models, and applying diagnostic tools
      to check the adequacy of the models. The final analysis used autoregressive
      Poisson models allowing for overdispersion. Effects were reported as relative
      risks contrasting defined increases in the corresponding pollutant levels. Each
      participating group applied the analyses to their own data. CONCLUSIONS: This
      methodology enabled results from many different European settings to be
      considered collectively. It represented the best available compromise between
      feasibility, comparability, and local adaptibility when using aggregated time
      series data not originally collected for the purpose of epidemiological studies.

PMID- 8758220
TI  - Short term effects of air pollution on emergency hospital admissions for
      respiratory disease: results of the APHEA project in two major cities in The
      Netherlands, 1977-89.
AB  - STUDY OBJECTIVE: To assess the short term relationship between air pollution and
      the daily number of emergency hospital admissions for respiratory disease.
      DESIGN: Data were analysed using autoregressive Poisson regression allowing for
      overdispersion and controlling for possible confounding factors such as seasonal
      and other chronological variables, meteorological factors, and influenza
      epidemics. SETTING: The two major cities in The Netherlands-Amsterdam (694,700
      inhabitants) and Rotterdam (576,200 inhabitants). PARTICIPANTS AND MEASUREMENTS:
      Emergency hospital admissions for respiratory diseases, registered on a daily
      basis by the National Medical Registration, for the period 1977-89 were used. ICD
      9 codes included were: respiratory (460-519), chronic obstructive pulmonary
      disease (490-492, 494, 496), and asthma (493). The mean (range) of the total
      daily number of admissions for these three classifications were as follows: 6.70
      (0-23), 1.74 (0-9) and 1.13 (0-7) respectively in Amsterdam and 4.79 (0-19), 1.57
      (0-9), and 0.53 (0-5) in Rotterdam. Air pollution measurements were provided by
      the National Institute of Public Health and Environmental Protection. In The
      Netherlands, air pollution is at a low to moderate ("summer type") or a low
      ("winter type") level. The levels in Amsterdam and Rotterdam did not differ much
      for the "summer type". For 1977-89 the mean (range) values of ozone (O3), the
      "summer type" pollutant (O3-8 h), were 86 (0-252) micrograms/m3 in Amsterdam and
      82 (0-286) micrograms/m3 in Rotterdam. The mean (range) of the values "winter
      type", pollutant, sulphur dioxide (SO2-24 h), were 38 (0-381) micrograms/m3 in
      Amsterdam and 50 (1-379) micrograms/m3 in Rotterdam. For black smoke (BS-24 h),
      values were 14 (1-84) micrograms/m3 and 28 (1-144) micrograms/m3 respectively
      (1986-89). MAIN RESULTS: Ozone had a non-significant positive effect on the
      number of respiratory emergency admissions in summer in people aged > or = 65
      years (relative risk for a 100 micrograms/m3 increase in O3-8 h of 1.127 (0.983,
      1.292) in Amsterdam and a significant positive effect of 1.344 (1.097, 1.647) in
      1977-81 in Rotterdam). Sulphur dioxide did not show any clear effects; in
      Amsterdam a significant negative effect was even found. The same was true for
      nitrogen dioxide in Amsterdam; in Rotterdam, however, nitrogen dioxide showed non
      significant positive effects (RR 0.965, 1.342). Black smoke did not show any
      clear effects in Amsterdam; in Rotterdam it was positively but not significantly
      related to the number of admissions. CONCLUSIONS: The results show that the
      relation between short term air pollution and emergency hospital admissions is
      not always consistent at these rather low levels of daily hospital admissions and
      of air pollution.

PMID- 8758221
TI  - Short term effects of air pollution on mortality in the city of Lyon, France,
      1985-90.
AB  - OBJECTIVE: The short term association between daily mortality and ambient air
      pollution in the city of Lyon, France (population, 410,000) between 1985 and 1990
      was assessed using time series analysis. DESIGN: This study followed the
      standardised design and statistical analysis (Poisson regression) that
      characterise the APHEA project. METHODS: Four categories of cause of death were
      studied: total (minus external causes), respiratory, cardiovascular, and
      digestive causes (as a control condition). RESULTS: No association was found with
      any cause of death for nitrogen dioxide (NO2) and ozone (O3), nor, for any
      pollutant, for digestive conditions. Sulphur dioxide (SO2) and, to a much lesser
      degree, suspended particles (PM13), were significantly related to mortality from
      respiratory and cardiovascular conditions. The relative risk (RR) of respiratory
      deaths associated with a 50 micrograms/m3 increment of mean daily SO2 over the
      whole period was 1.22 (95% CI 1.05, 1.40); the RR for cardiovascular deaths was
      1.54 (1.22, 1.96). The corresponding RRs for PM13 were 1.04 (1.00, 1.09) for
      respiratory mortality and 1.04 (0.99, 1.10) for cardiovascular deaths.
      CONCLUSIONS: The effects of particulates were slightly increased during the cold
      season. When particulates concentrations were greater than 60 micrograms/m3, the
      joint SO2 effect was increased, suggesting some interaction between the two
      pollution indicators. These results agree with other studies showing an
      association between particulate pollution and daily mortality; however, they also
      suggest the noxious effect of SO2.

PMID- 8758222
TI  - Short term effect of air pollution on mortality in Polish urban populations--what
      is different?
AB  - STUDY OBJECTIVE: To assess, within the multinational European Community funded
      APHEA project, the relationship between daily ambient air pollution with sulphur
      dioxide (SO2) and black smoke (BS) and the daily number of deaths from all causes
      except external, from cardiovascular diseases, and from respiratory diseases
      taking into account several possible confounding factors. DESIGN: Time series
      analysis with the application of Poisson regression to the counts of daily number
      of deaths from selected causes over several years. Data were obtained from the
      computer files of individual death records in four Polish cities. Criteria
      developed for all the centres participating in the project were applied to the
      process of model building. SETTING: Four Polish cities - Cracow (period 1977-89),
      Lodz (1977-90), Poznan (1983-90), and Wroclaw (1979-89). SUBJECTS: Permanent
      residents of the cities who died in a city of residence or in a surrounding
      region during the study period. MAIN RESULTS: There were significant positive
      associations between mortality from all causes excluding external ones and SO2
      and BS in Cracow and in Lodz and between mortality from cardiovascular diseases
      and SO2 in Cracow alone. In other cities the association was either non
      significant or significant but in the opposite direction. No significant positive
      association was found between respiratory deaths and these pollutants.
      CONCLUSIONS: Short term effect of air pollution on mortality in Polish urban
      population cannot be ignored. However, differences observed between the cities
      suggest that the association may be not so straightforward and therefore there is
      a need of further studies to identify additional factors that may modify and
      confound the association.

PMID- 8758223
TI  - Short term respiratory health effects of ambient air pollution: results of the
      APHEA project in Paris.
AB  - STUDY OBJECTIVE: To quantify the short term respiratory health effects of ambient
      air pollution in the Paris area. DESIGN: Time series analysis of daily pollution
      levels using Poisson regression. SETTING: Paris, 1987-92. MEASUREMENTS AND MAIN
      RESULTS: Air pollution was monitored by measurement of black smoke (BS) (15
      monitoring stations), sulphur dioxide (SO2), nitrogen dioxide (NO2), particulate
      matter less than 13 microns in diameter (PM13), and ozone (O3) (4 stations).
      Daily mortality and general admissions to public hospitals due to respiratory
      causes were considered. The statistical analysis was based on a time series
      procedure using linear regression modelling followed by a Poisson regression.
      Meterological variables, epidemics of influenza A and B, and strikes of medical
      staff were included in the models. The mean daily concentration of PM13 and daily
      1 hour maximum of SO2 significantly affected daily mortality from respiratory
      causes. An increase in the concentration of PM13 of 100 micrograms/m3 above its
      5th centile value increased the risk of respiratory death by 17%. PM13 and BS
      were also associated with hospital admissions due to all respiratory diseases
      (4.1% increased risk when the BS level exceeded its 5th centile value by 100
      micrograms/m3). SO2 levels consistently influenced hospital admissions for all
      respiratory diseases, chronic obstructive pulmonary disease, and asthma. Asthma
      was also correlated with NO2 levels. CONCLUSIONS: These results indicate that
      even though the relative risk is weak in areas with low levels of pollution,
      ambient air pollution, and especially particulate matter and SO2, nonetheless
      require attention because of the number of people exposed and the existence of
      high risk groups.

PMID- 8758224
TI  - Daily mortality and "winter type" air pollution in Athens, Greece--a time series
      analysis within the APHEA project.
AB  - STUDY OBJECTIVE: There is evidence that air pollution in Athens between 1975 and
      1987 had adverse short term health effects. The short term effects of "winter
      type" air pollution on the daily total number of deaths are investigated for the
      period 1987-91 as part of the European Community multi centre APHEA project.
      DESIGN: A temporal study using aggregated data is presented. The associations of
      the daily time series of three pollutants, sulphur dioxide (SO2), black smoke
      (BS), and carbon monoxide (CO) and the daily total number of deaths in the Athens
      area were assessed. DATA AND METHODS: The average measurement from three stations
      was used for each pollutant. The daily number of deaths was recorded from the
      Athens Town Registry and the registries of the 18 municipalities contiguous to
      Athens. Data on the mean daily temperature (degree C) and relative humidity (%)
      were also used. Poisson autoregressive models that also allowed for
      overdispersion were used. Seasonality, other long term patterns, temperature,
      humidity, day of the week, and holidays were adjusted for. Several a priori
      defined pollutant transformations and lags were investigated. One day
      measurements as well as cumulative exposure effects were assessed. Effect
      modification by season as well as among pollutants was tested. MAIN RESULTS:
      Linear terms were used for all pollutants. The magnitude of the effect was
      greater at lags 0 for CO and 1 for BS and SO2 gradually declining after lag 1.
      For an increase of 100 micrograms/m3 in SO2 and BS there were corresponding
      increases (95% CI) of 12% (7%, 16%) and 5% (3%, 8%) in the daily total numbers of
      deaths, while for an increase of 10 micrograms/m3 in CO the increase (95% CI) in
      the daily total number of deaths was 10% (5%, 15%). A significant interaction of
      the effects of SO2 with season were found. The strongest effect was observed
      during the winter, when higher levels of SO2 were observed. A stronger effect of
      SO2 on the daily total number of deaths was observed when the levels of BS were >
      100 micrograms/m3. CONCLUSIONS: These results strengthen the evidence of a causal
      association between ambient particle, SO2, or CO levels in the air and the daily
      total number of deaths and points to an important public health issue for the
      Athens population.

PMID- 8758225
TI  - Daily mortality and air pollutants: findings from Koln, Germany.
AB  - STUDY OBJECTIVE AND DESIGN: For the APHEA study, the short term effects of air
      pollutants on human health were investigated in a comparable way in various
      European cities. Daily mortality was used as one of the health effects
      indicators. This report aims to demonstrate the steps in epidemiological model
      building in this type of time series analysis aimed at detecting short term
      effects under a poisson distribution assumption and shows the tools for decision
      making. In addition, it assesses the impact of these steps on the pollution
      effect estimates. SETTING: Koln, Germany, is a city of one million inhabitants.
      It is densely populated with a warm, humid, unfavourable climate and a high
      traffic density. In previous studies, smog episodes were found to increase
      mortality and higher sulphur dioxide (SO2) levels were connected with increases
      in the number of episodes of croup. PARTICIPANTS, MATERIALS AND METHODS: Daily
      total mortality was obtained for 1975-85. SO2, total suspended particulates, and
      nitrogen dioxide (NO2) data were available from two to five stations for the city
      area, and size fractionated PM7 data from a neighbouring city. The main tools
      were time series plots of the raw data, predicted and residual data, the partial
      autocorrelation function and periodogram of the residuals, cross correlations of
      prefiltered series, plots of categorised influences, chi 2 statistics of
      influences and sensitivity analyses taking overdispersion and autocorrelation
      into account. RESULTS AND CONCLUSIONS: With regard to model building, it is
      concluded that seasonal and epidemic correction are the most important steps. The
      actual model chosen depends very much on the properties of the data set. For the
      pollution effect estimates, trend, season, and epidemic corrections are important
      to avoid overestimation of the effect, while an appropriate short term meterology
      influence correction model may actually prevent underestimation. When the model
      leaves very little over-dispersion and autocorrelation in the residuals, which
      indicates a good fit, correction for them has consequently little impact. Given
      the model, most of the range of SO2 values (5th centile to 95th centile) led to a
      3-4% increase in mortality (significant), particulates led to a 2% increase
      (borderline significant, less data than for SO2), and NO2 had no relationship
      with mortality (measurements possibly not representative of actual exposure).
      Effects were usually delayed by a day.

PMID- 8758226
TI  - Asthma and ambient air pollution in Helsinki.
AB  - OBJECTIVE: To study whether ambient air levels of sulphur dioxide (SO2), nitrogen
      dioxide (NO2), total suspended particulates (TSP), and ozone (O3) affect the
      number of hospital admissions for asthma. DESIGN: The associations between the
      daily number of admissions and air pollutants were analysed with Poisson
      regression, taking into account potential confounding factors by using the
      standardised protocol of the APHEA project. SETTING: Helsinki, Finland, 1987-89.
      PATIENTS AND MEASUREMENTS: Patients admitted to hospitals through emergency rooms
      because of asthma (n = 2421). The daily mean concentration was 13-25
      micrograms/m3 for SO2, 33-41 micrograms/m3 for NO2, 19-41 micrograms/m3 for O3,
      and 58-109 micrograms/m3 for TSP during the different seasons. Values are means
      for various stations. The daily mean temperature during the three year period was
      +5.4 degrees C (range -37-27 degrees C). MAIN RESULTS: Positive associations with
      admissions were observed for O3 levels in all children under 14 years, and for
      SO2 levels in 15-64 year olds and among those older than 64. Significant
      associations were also seen between admissions for digestive tract diseases (the
      control) and O3 levels. This suggests that the modelling, which proved to be
      problematic, was unsatisfactory, or it may be a statistical coincidence. A rise
      in temperature was associated with a low number of admissions for asthma among 0
      14 year olds and among 15-64 year olds, whereas humidity did not have a
      significant effect on the number of admissions. CONCLUSIONS: It is possible than
      even low level pollution may increase hospital admissions for asthma. However,
      definitive conclusions will be justified only after meta-analysis comprising
      several studies. The methodology was seen to have a strong effect on the results
      and standardised methods, possibly differing from those for the study concerning
      mortality, are needed to investigate the association between morbidity and
      ambient air pollutants.

PMID- 8758227
TI  - Effects of air pollution on daily hospital admissions for respiratory disease in
      London between 1987-88 and 1991-92.
AB  - STUDY OBJECTIVE: To investigate whether air pollution levels in London have short
      term effects on hospital admissions for respiratory disease. DESIGN: Poisson
      regression analysis of daily counts of hospital admissions, adjusting for effects
      of trend, seasonal and other cyclical factors, day of the week, holidays,
      influenza epidemic, temperature, humidity, and autocorrelation. Pollution
      variables were particulates (black smoke: BS), sulphur dioxide (SO2), ozone (O3),
      and nitrogen dioxide (NO2), lagged 0-3 days. SETTING AND PATIENTS: All immediate
      admissions for respiratory disease (ICD 460-519) to hospitals in London health
      districts in the five years April 1987 to February 1992 for all ages and the 0
      14, 15-64, and 65+ age groups. MAIN RESULTS: O3 (lagged one day) was
      significantly associated with an increase in daily admissions among all age
      groups, except the 0-14 group, and this effect was stronger in the "warm" season
      (April-September). In this season, the relative risks of admission associated
      with an increase in 8 hour O3 levels of 29 ppb (10th to 90th centile) were 1.0483
      (95% CI 1.0246, 1.0726), 1.0294 (0.9930,1.0672), 1.0751 (1.0354,1.1163), and
      1.0616 (1.0243,1.1003) for all ages and age groups 0-14, 15-64, and 65+
      respectively. Very few significant associations were observed with the other
      pollutants, though these tended to be positive. Controlling for other pollutants
      made little difference to the O3 coefficients. There was evidence of a threshold
      at about 40-60 ppb O3 (maximum hourly or maximum 8 hour). CONCLUSIONS: O3 levels
      in London have a small but significant effect on hospital admissions for
      respiratory disease at all ages. The possible role of aerollergen as a
      confounding factor needs to be examined. Unlike other cities where similar
      effects have been reported, little or no effect of particulates was observed in
      London.

PMID- 8758228
TI  - Short term effects of urban air pollution on respiratory health in Milan, Italy,
      1980-89.
AB  - STUDY OBJECTIVE: To investigate the association between daily urban air pollution
      and acute effects on respiratory health. STUDY DESIGN: Time series analysis
      following the procedure defined in the APHEA protocol. SETTING: City of Milan,
      Italy, from 1980-89. Two air pollutants, total suspended particulates (TSP) and
      sulphur dioxide (SO2), and two health outcomes, deaths and hospital admissions
      were considered. The last was analysed according to two age groups. SUBJECTS:
      Daily deaths and general hospital admissions for respiratory causes in residents
      who died in Milan or were admitted to local hospitals in that city. MAIN RESULTS:
      There was an increased risk of respiratory death and of hospital admission
      associated with increased concentrations of SO2 and TSP. The relative risks were
      similar for both pollutants, and were higher for respiratory deaths than for
      hospital admissions. No changes in relation to season were seen in the SO2 effect
      on respiratory deaths, but there was a suggestion of a higher effect on hospital
      admissions in the cool months. The seasonal pattern of the TSP effect was
      inconsistent: for mortality it was higher in the warm period while for hospital
      admissions it seemed to be higher in the cool months. This last result might be
      due to chance, although some role could have been played by the hospital
      admission data on all general admissions for respiratory causes (ICD-9: 460-519)
      as these are a much less specific end point. CONCLUSION: In Milan, a positive
      association was found between the daily SO2 or TSP concentrations and the number
      of deaths or hospital admissions for respiratory causes. This confirms results
      from other European and North American cities.

PMID- 8758230
TI  - The C-ASE Project: computer-assisted simulated examination.
AB  - Simulations of clinical scenarios for medical education can take a number of
      forms, including paper-based tutorials, interactive computer programs, and
      Standardized Patients (SPs). The fidelity of a simulation to the situation it
      mimics may have a great deal to do with its educational effectiveness. It was
      hypothesized that it is possible to create simulation experiences on a
      microcomputer that occupy a middle ground between the low-fidelity simulation of
      paper-based tutorials and many interactive computer programs, and high-fidelity
      simulation of SPs. The C-ASE (computer-assisted simulated examination) project,
      developed to test this hypothesis, incorporates a simulated three-dimensional
      environment and digital video of patients and clinic staff.

PMID- 8758229
TI  - Air pollution and mortality in Barcelona.
AB  - STUDY OBJECTIVES: Studies conducted in Barcelona reported a short term relation
      between daily air pollutant values and emergency department admissions for
      exacerbation of chronic obstructive pulmonary diseases and asthma. Air pollution
      in Barcelona is mainly generated by vehicle exhaust and is below the World Health
      Organization air quality guidelines. The acute relation between air pollution and
      mortality was assessed. DESIGN: Daily variations in total mortality, mortality in
      subjects older than 70 years, and cardiovascular and respiratory mortality were
      related with daily variations in air pollutants for the period 1985-91, using
      autoregressive Poisson regression models that allow to control for temperature,
      relative humidity and variables handling temporal and autoregressive patterns.
      MAIN RESULTS: Black smoke and sulphur dioxide (SO2) were related to total
      mortality (relative risks (RR) for 100 micrograms/m3 = 1.07 and 1.13
      respectively), elderly mortality (RR = 1.06 and 1.13), cardiovascular mortality
      (RR = 1.09 and 1.14), and respiratory mortality (RR = 1.10 and 1.13); all the
      associations being statistically significant, except for respiratory mortality (p
      = 0.07). The association between SO2 and respiratory mortality was stronger in
      summer (1.24, p < 0.01) than in winter (1.08, p > 0.1). Oxidant pollutants
      (nitrogen dioxide and ozone) were positively related with elderly mortality (RR =
      1.05 and 1.09, respectively) and cardiovascular mortality (RR = 1.07 and 1.09)
      during the summer (p < 0.05), but not during the winter. CONCLUSIONS: Current air
      pollutant levels were related to mortality in Barcelona. These results were
      consistent with similar studies in other cities and coherent with previous
      studies with emergency room admissions in Barcelona.

PMID- 8758231
TI  - Digital image databasing.
AB  - A previous two-part article by Simon Brown described the acquisition, editing,
      compression and initial storage of digital images taken in the clinical studio.
      Due to the higher-than-expected demand for this clinical service, additional
      factors had to be considered when dealing with large numbers of images. These
      included storage on writable compact disc (CD) drives and a system for retrieving
      images from these devices which was flexible enough to handle the requirements of
      different specialities and be usable by all medical illustration staff.

PMID- 8758232
TI  - 'Funnel light' photography of metallic objects (designed by Leon J. LeBeau).

PMID- 8758233
TI  - Neurofibromatosis: Von Recklinghausen's disease.

PMID- 8758234
TI  - An appreciation of the life and work of John Arthur Fairfax Fozzard MA Hon FRPS
      1905-1993.

PMID- 8758235
TI  - GMC Guidance on filming patients for television programmes.

PMID- 8758236
TI  - PSA and prostate cancer diagnosis.

PMID- 8758237
TI  - Ifosfamide and paediatrics: should this marriage be saved?

PMID- 8758238
TI  - Accuracy of admission and clinical diagnosis of tumours as revealed by 2000
      autopsies.
AB  - Admission, clinical and autopsy diagnoses of tumour were computed in 2000
      consecutive cases, aged 30-80 years, using data collected in two university
      pathology departments in Budapest, Hungary. Based on diagnosis of tumour,
      regardless of site, as the underlying cause of death false-negative rates were
      37.4% at admission and 8.8% clinically. Corresponding false-positive rates were
      8.4 and 9.1%. General practitioners who correctly diagnosed a tumour as the cause
      of the terminal illness identified the primary site wrongly in 20.6% (90/436) of
      cases. Hospital clinicians did so in 20.4% (130/636) of cases. Overall, of site
      specific tumours considered as the underlying cause of death at autopsy, 27.4%
      were incorrectly diagnosed clinically and 50.4% at admission. Diagnostic errors
      were particularly common for tumours of the lung, liver, ovary and gall bladder.
      Graduate and postgraduate education, planning of the health care system and
      quality of cancer care may benefit from statistical data derived from autopsy
      diagnoses.

PMID- 8758239
TI  - Carcinoid of the pancreas: clinical characteristics and morphological features.
AB  - The classical carcinoid tumour (WHO) of the pancreas is extremely rare and its
      diagnosis may puzzle physicians and pathologists. Here, 29 previously published
      cases of pancreatic carcinoid tumours, including one new case, are reviewed.
      Literature research was done using MedLine from 1966 to 1995. Pancreatic
      carcinoids produce an atypical carcinoid syndrome. Skin flushing was reported in
      only 34%. The main symptom was pain, followed by diarrhoea and weight loss.
      Elevated urinary 5-HIAA levels were found in 85% (17/20). The immunocytochemical
      sensitivity for serotonin was 100% (11/11). The diagnosis of pancreatic carcinoid
      tumour is based on the typical endocrine histological features together with
      increased serotonin metabolism. Generally, the slow growth rate and late invasion
      of adjacent organs render local resection possible, but the high incidence of
      distant metastases (69%) prevents long-term survival in the majority of patients.
      The possible role of the Octreoscan, a new radionuclide imaging technique, is
      discussed with regard to this tumour entity.

PMID- 8758240
TI  - Locoregional chemotherapy for adjuvant treatment of colorectal adenocarcinoma.
AB  - Adjuvant chemotherapy with 5-fluorouracil (5-FU) and levamisole administered
      intravenously for 1 year has proved to be effective after curative surgical
      resection of Dukes' stage C colon carcinomas. Locoregional chemotherapy aims at
      delivering drugs directly into the abdominal cavity or the liver using either
      intraperitoneal or intraportal route of administration. Theoretically, these
      routes of administration have several advantages. The drugs can be delivered at a
      high dose concentration to the most common site of recurrence (i.e. peritoneum
      and liver) with decreased systemic toxicity. This article reviews the present
      status of intraportal and intraperitoneal chemotherapy as adjuvant postoperative
      treatment for colorectal carcinoma with special attention to the results of
      prospective randomised trials. Some positive results confirm that both route of
      administration represent promising methods for adjuvant chemotherapy. However,
      currently there are insufficient data on which to make a clear-cut conclusion on
      real benefits. New trials are currently in progress to test new modalities using
      different drugs or different drug combinations, using both locoregional and
      systemic treatments, and may prove to be more effective than systemic
      chemotherapy alone in the adjuvant treatment of colorectal cancers.

PMID- 8758241
TI  - Value of PSA (prostate-specific antigen) in the detection of prostate cancer in
      patients with urological symptoms. Results of a multicentre study.
AB  - The aim of this multicentre study was to assess the usefulness of prostate
      specific antigen (PSA) as a diagnostic procedure for prostate cancer in patients
      with urological symptoms, and compare it with digital rectal examination (DRE).
      The study included 2054 urological patients, aged over 50 years, and PSA levels
      were measured using an automated enzyme immunoassay. In the 680 cases with PSA
      levels > 3 micrograms/l and/or suspect DRE, transrectal ultrasound and prostate
      biopsy were also performed, leading to a diagnosis of cancer in 131 cases. The
      sensitivity of PSA was higher (95% and 73% for the cut-off values of 3 and 10
      micrograms/l, respectively) than DRE (69%), both parameters being complementary.
      When DRE and PSA (> 10 micrograms/l) were combined, 118 cancers were diagnosed,
      with a PPV of 37%. We recommend using PSA and DRE in combination as a diagnostic
      procedure for prostate cancer in urological patients, since both methods are
      complementary.

PMID- 8758242
TI  - Genitourinary group phase II study of chemotherapy in stage T3-4 N0-X M0
      transitional cell cancer of the bladder: prognostic factor analysis.
AB  - The aim of this study was to examine prognostic factors for survival of patients
      with invasive bladder cancer who had received neoadjuvant chemotherapy followed
      by further treatment. From 1986 to 1990, 149 eligible patients with T3-4 N0-X M0
      bladder cancer were entered into a phase II trial of neoadjuvant chemotherapy,
      consisting of cisplatin and methotrexate. Patients received two or four courses
      of chemotherapy, depending on the absence or presence, respectively, of a major
      clinical response after two courses. 136 patients were evaluable for clinical
      response after two courses of chemotherapy, and 75 patients were evaluable for
      pathological response after two or four courses. A multivariate analysis, based
      on pretreatment variables and the post-treatment variables, clinical response and
      pathological response, showed that performance status, tumour size and clinical
      response after two courses of chemotherapy were the only independent prognostic
      factors for all eligible patients. A second multivariate analysis in the selected
      subgroup of patients, who underwent a cystectomy, showed that the G-cagetory and
      pathological response were the only independent prognostic factors. In
      conclusion, in this group of patients, the response to chemotherapy was a strong
      and independent prognostic factor in addition to other independent variables.
      However, it was not accurate or strong enough to allow an impact on the choice of
      locoregional therapy.

PMID- 8758243
TI  - Karnofsky and ECOG performance status scoring in lung cancer: a prospective,
      longitudinal study of 536 patients from a single institution.
AB  - The Karnofsky's index of performance status (KPS) and the Eastern Cooperative
      Oncology Group Performance Status Scale (ECOG PS) are widely used methods of
      assessing the functional status of cancer patients. In this study, we compare
      their predictive validity, and suggest a table of transformation between scales.
      536 consecutive lung cancer patients were assigned both KPS and ECOG PS scores
      before, during and after treatment (in all, 1656 assignments). Patients were
      accurately staged at diagnosis, and carefully re-evaluated at each follow-up
      visit. Multiple clinical, laboratory and instrumental data were recorded along
      with performance status assessments. Survival times were measured from the
      pathological diagnosis. KPS and ECOG PS assignments were strongly related to each
      other (Spearman R = -0.869). Correlation between scales persisted unchanged in
      pretreatment and post-treatment assessments, advanced and limited diseases,
      response or non-response to treatment, and different assessors (R indices ranging
      from -0.825 to -0.901). A three-point conversion table showed the highest rate of
      success with an overall percentage of agreement exceeding 84% (grade 1: KPS =
      100, 90, 80 and ECOG PS = 0, 1; grade 2: KPS = 70, 60 and ECOG PS = 2; grade 3:
      KPS < 60 and ECOG PS = 3, 4). Both univariate and multivariate analyses of
      survival documented the predictive validity of the two scales. However, KPS
      showed less ability than ECOG PS to discriminate patients with different
      prognosis. Because of the better predictive ability shown in this study, ECOG PS
      should be preferred to KPS. A general consensus on the scale to use could avoid
      problems of conversion, which is not always easy and free of errors.

PMID- 8758244
TI  - Effect of home care on the place of death of advanced cancer patients.
AB  - This study presents a prospective evaluation of the home care programme for
      patients with advanced cancer at the National Cancer Institute of Milan.
      Demographic, psychosocial and physical variables were evaluated. The Therapy
      Impact Questionnaire was used for symptom and quality of life assessment. The
      association of clinical and demographic variables with the place of death was
      investigated, considering that the aim of the home care programme is to follow up
      patients until death in their houses. Eighty-six per cent (86%) of patients died
      at home and 14% in hospitals. Multivariate analysis showed that only a higher
      degree of family support was associated with home death. Several changes in
      symptoms and quality of life items scores were seen, pain improved while physical
      debility and cognitive functions worsened throughout the home care duration to
      death. High intensity pain and dyspnoea were still present in, respectively, 23.8
      and 15.3% of patients in the last week of life. Psychological distress was high
      at the end of life and did not seem to be affected by treatment. Home care is a
      feasible alternative for implementing palliative care in a selected population of
      patients with advanced cancer. Palliation of physical symptoms is more easily
      achieved than the control of psychological suffering. Family and economical
      issues implied by home care models should be part of the discussion in
      implementing palliative care for advanced cancer patients.

PMID- 8758245
TI  - Immunohistochemical evaluation of multiple biological markers in ductal carcinoma
      in situ of the breast.
AB  - In order to obtain prognostic clinicopathological information, 49 cases of pure
      ductal carcinoma in situ of the breast (DCIS), were evaluated for the
      immunohistochemical expression of potential predictor markers including c-erbB-2
      oncogene product, p53 protein, oestrogen (ER) and progesterone (PR) receptors,
      oestrogen-regulated proteins pS2 and cathepsin-D (cath-D), CD44 protein and 67
      kDa laminin receptor (MLuC5). Immunohistochemical findings were compared with
      conventional pathological parameters, clinical findings, and the clinical outcome
      of the patients. When markers were matched to each other, statistical analyses
      provided a significant positive correlation between c-erbB-2 overexpression and
      p53 positivity (P < 0.01) and between ER and PR (P < 0.01), ER, PR and pS2 (P <
      0.01), pS2 and MLuC5 (P < 0.05). Significant negative correlations between c-erbB
      2 overexpression and ER (P < 0.05), PR (P < 0.01) and pS2 (P < 0.01) positivity
      was also observed. Data on the relationship between marker status and
      pathological findings revealed a significant positive trend between c-erbB-2,
      p53, and increased grade values (P < 0.05) and opposite results with PR receptor
      expression (P < 0.01). c-erbB-2 overexpression was further significantly
      associated with comedotype carcinoma (P < 0.05) and distribution of disease in
      confluent neoplastic ducts (P < 0.01). Although no statistically significant
      correlation among biological markers expression, clinical findings and outcome
      was demonstrated, overall this study indicates that tumour cells from a subset of
      DCIS, which includes comedotype carcinoma, express significantly unfavourable
      prognostic factors.

PMID- 8758246
TI  - Pre-operative serum levels of CA 242 and CEA predict outcome in colorectal
      cancer.
AB  - The prognostic value of the preoperative serum levels of CA 242 and CEA in
      patients with colorectal cancer was investigated. The serum concentrations of CA
      242 and CEA were determined from preoperative serum samples of 259 patients with
      colorectal cancer (39 Dukes' A, 100 Dukes' B, 59 Dukes' C and 61 Dukes' D).
      Survival data of these patients were obtained to the end of 1993. There was a
      significantly longer survival in patients with a CA 242 level below 20 U/ml
      compared with patients with an elevated serum level. A difference was seen in
      overall survival (P < 0.0001), and in Dukes' B (P = 0.016) and Dukes' D (P =
      0.009) stages. In Dukes' A and C colorectal cancer, the difference was not
      significant (P = 0.67 and P = 0.07, respectively). When 5 ng/ml was used as cut
      off value for CEA, there was a significant difference in overall survival (P <
      0.0001), but not within the different Dukes' stages. The prognosis was
      considerably worse in patients with concomitant elevation of CA 242 and CEA,
      compared with the prognosis of patients with normal levels or only one marker
      elevated (P < 0.0001). When analysing according to stage, a significant
      difference was seen in Dukes' B (P = 0.0004) and Dukes' C (P = 0.0007) stages. In
      a multivariate analysis, CA 242 was an independent prognostic factor (P <
      0.0001). CEA was also an independent prognostic factor (P = 0.03), but only after
      exclusion of CA 242. Concomitant rise of CA 242 and CEA was found to be a strong
      independent prognostic factor (P < 0.0001). This study shows that the pre
      operative serum CA 242 level is an independent prognostic factor in patients with
      colorectal cancer and that the prognosis of patients having a concomitant pre
      operative elevation of CA 242 and CEA is poor.

PMID- 8758247
TI  - Economic analysis of the use of recombinant human granulocyte colony stimulating
      factor in autologous bone marrow transplantation.
AB  - The aim of this study was to assess the economic impact of the use of granulocyte
      colony stimulating factor (RHu-G-CSF) in patients treated by autologous bone
      marrow transplantation (ABMT) for lymphomas. Demographic, clinical and economic
      data were collected retrospectively from a random sample of 55 patients in four
      French centres who underwent ABMT (usual care) without or with administration of
      RHu-G-CSF over a period of 100 days post-ABMT. The patients treated with RHu-G
      CSF had a shorter period of infection, neutropenia and severe neutropenia (P <
      0.05) when compared with usual care recipients. Compared to usual care, the use
      of G-CSF was associated with a 3% reduction in total cost of care for ABMT over
      100 days post-ABMT or US$1316, including RHu-G-CSF cost. This cost reduction was
      mainly due to a reduced length of stay in hospital and fewer laboratory tests.

PMID- 8758248
TI  - Monitoring the action of clodronate with type I collagen metabolites in multiple
      myeloma.
AB  - In our previous double-blind trial, we reported that clodronate reduced the
      incidence of bone lesions, fractures, pain and hypercalcaemia in multiple
      myeloma. Recently, it has been assumed that the antiresorptive effect of
      bisphosphonates on the osteoclasts is mediated through the osteoblasts. We
      therefore determined, in 244 patients of the same trial, serum assays of
      aminoterminal propeptide of type I procollagen (PINP) and type I collagen
      degradation product (ICTP). PINP is an early synthesis product of proliferating
      osteoblasts, in comparison to the alkaline phosphatase (AP) which is secreted by
      differentiated osteoblasts during the maturation phase of collagen. ICTP
      circulates in serum when old bone is resorbed. Our results indicate that after 25
      months, the PINP levels decreased in the clodronate group (from 68.9 +/- 4.4
      micrograms/l to 37.2 +/- 3.5 micrograms/l; P < 0.001) but not in the control
      group (from 61.5 +/- 3.2 micrograms/l to 69.3 +/- 7.5 micrograms/l; P < NS). The
      fall in the ICTP levels was markedly steeper in the patients receiving clodronate
      (from 8.38 +/- 0.80 micrograms/l to 4.58 +/- 0.32 micrograms/l; P < 0.01) than
      placebo (from 7.84 +/- 0.53 micrograms/l to 6.45 +/- 0.95 micrograms/l; P = NS).
      A significant difference between the study groups was seen at 4 months in the
      PINP, at 7 months in the ICTP and at 13 months in the AP levels, suggesting that
      clodronate affected through the proliferating osteoblasts, the osteoclasts, and
      through the osteoclasts, the differentiated osteoblasts. High baseline ICTP, PINP
      and AP levels indicated a poor prognosis. The decrease of the markers by
      clodronate was more marked in survivors than in non-survivors.

PMID- 8758249
TI  - An open phase I study to assess the biological effects of a continuous
      intravenous infusion of Interleukin-3 followed by Granulocyte Macrophage-Colony
      Stimulating Factor.
AB  - To assess any synergistic stimulatory effect in vivo of Interleukin 3 (IL-3) and
      Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) upon white cell and
      platelet counts, toxicity and antitumour effect, we conducted this phase I study.
      IL-3 0.25, 0.5 or 5 micrograms/kg/day for 1, 4 or 7 days was given by continuous
      intravenous (i.v.) infusion to 35 patients with advanced malignancy. 21 of the 35
      patients also received sequential or overlapping treatment with continuous i.v.
      infusion of GM-CSF 1 or 3 micrograms/kg/day for up to 10 days. Monotherapy with
      IL-3 producted significant dose related increases in platelets and white cell
      counts. Combinations of IL-3 and GM-CSF also produced increases in white cell
      counts, but these were no greater than would be expected following GM-CSF
      treatment alone. There was a trend for platelets to increase more in patients
      receiving IL-3 and GM-CSF than those receiving IL-3 alone, but this did not reach
      statistical significance. In general, IL-3 and combinations of IL-3 and GM-CSF
      were well tolerated and the most common side-effect was fever. A maximum
      tolerated dose was not reached and antitumour effects were not seen. Future
      studies using combinations of IL-3 5 micrograms/kg/day and GM-CSF 3
      micrograms/kg/day may help to define the optimal therapeutic regimen.

PMID- 8758250
TI  - Ifosfamide nephrotoxicity: limited influence of metabolism and mode of
      administration during repeated therapy in paediatrics.
AB  - This study investigated the relationship between both acute and chronic
      nephrotoxic effects of ifosfamide (IFO) and its metabolism. 15 paediatric
      patients (4 girls) were investigated. Each received 6-9 g/m2 IFO over 15 days,
      repeated every 3 weeks for up to 16 courses. The pharmacokinetics and metabolism
      of IFO were measured during its administration, either as a continuous 72 h
      infusion or as three bolus doses of 3 g/m2 on consecutive days. In 8 patients,
      the metabolism of IFO was investigated during one early course and one late
      course to determine the magnitude of any changes following repeated
      administration. Acute measures of renal toxicity were not correlated with any of
      the IFO pharmacokinetic or metabolic parameters in the same course, whether the
      drug was administered as a bolus or by continuous infusion. Chronic renal
      toxicity, determined 1 month (n = 13) or 6 months (n = 8) after treatment, did
      not correlate with any of the IFO pharmacokinetic or metabolic parameters in any
      individual course of treatment. The overall degree of nephrotoxicity, however,
      was correlated with the changes in metabolism between late and early courses (n =
      8). There was a negative correlation between the change in area under the curve
      of the dechloroethylated metabolites of IFO and the overall nephrotoxicity at 1
      month or 6 months after treatment (both r2 = 0.66, P = 0.014). The results imply
      that patients in whom metabolism via dechloroethylation decreases are at a
      greater risk of chronic nephrotoxicity. This is contrary to the hypothesis that
      the systemic production of chloroacetaldehyde is the mechanism by which IFO
      causes nephrotoxicity. The importance of acute and chronic changes in renal
      function for long-term outcome remains to be determined.

PMID- 8758251
TI  - Monitoring chemotherapy-induced hearing loss in children.

PMID- 8758252
TI  - An ecological study of cancer incidence and radon levels in South West England.
AB  - To investigate the relationship of domestic radon levels and cancer, the
      incidence of 14 major cancers in Devon and Cornwall were examined in relation to
      the local radon levels. Cancer registrations for 1989-1992 were provided by the
      South-Western Regional Cancer Registry. The average radon levels for postcode
      sectors were sorted into ten categories from low (< 40 Bq/m3) to extremely high
      (> or = 230 Bq/m3) and age-standardised incidence rates were calculated for each
      radon category. The incidence rates for lung cancer, where radon has been claimed
      to be a risk factor, were very similar across all domestic radon categories. Only
      non-melanoma skin cancers, showed a significant increase in incidence in the high
      radon postcode sectors (> or = 100 Bq/m3) compared with the low-radon sectors (<
      60 Bq/m3) and this effect was observed for both sexes. The remaining 12 cancer
      sites showed no significant trend in incidence rates with increasing radon
      concentration. There was no significant difference in corrected survival rates
      for any cancer site between the low- and high-radon areas. The possible
      contribution of confounding factors to the results of this study is discussed.

PMID- 8758253
TI  - Variations in the screening history and appropriateness of management of cervical
      cancer in South East England.
AB  - In seven health districts in southern England, an audit of the management of
      cervical cancer compared with regionally developed guidelines was undertaken
      between 1988 and 1991. Four hundred and sixty-nine regional residents were
      treated in the study district hospitals. 73 (15.6%) women were appropriately
      staged, with increasing likelihood of appropriate staging investigations observed
      with higher stages (P < 0.0001) and type of hospital [Teaching 23 (21%), Non
      Teaching with oncology support 11 (11.5%), Non-teaching 4 (7%), P < 0.0001] but
      with no change over the study period. There was no significant trend in the
      proportion of women treated appropriately over time, with 270 (59%) being
      appropriately treated, 91 (20%) under-treated and 98 (21%) over-treated overall.
      Appropriateness of treatment increased with higher stages (P < 0.0001) and
      hospital workload for cancer of the cervix (P = 0.038). Multivariable analysis
      indicated that survival independently and significantly decreased with age and
      stage, under-treatment and in cases where lymph nodes were involved or not
      examined. There was no change in the appropriateness of management over the 4
      years, with high levels of inappropriate care. Survival was not only influenced
      by biological and demographic factors, but by inappropriate care.

PMID- 8758254
TI  - DNA amplification on chromosome 3q26.1-q26.3 in squamous cell carcinoma of the
      lung detected by reverse chromosome painting.
AB  - Multiple genetic lesions have been reported in small cell lung carcinoma (SCLC),
      while considerably less information is available on squamous cell carcinoma
      (SCC). We used reverse chromosome painting to screen a total of nine SCCs for DNA
      amplifications. In three of the nine SCCs, hybridisation signals were found at
      chromosome region 3q26.1-q26.3, which does not contain any known oncogene. In one
      of the three SCCs, there were additional hybridisation signals at 1q, 5p and
      6p21.1. The high frequency of a consistent amplification (3q26.1-q26.3) in SCC
      strongly indicates a novel gene at 3q26.1-q26.3 that is important in the
      pathology of SCC.

PMID- 8758255
TI  - Prognostic and aetiological relevance of 8-hydroxyguanosine in human breast
      carcinogenesis.
AB  - In order to estimate the level of oxidative damage and its role in breast cancer,
      the promutagenic oxidative lesion, 8-hydroxy-2'-deoxyguanosine (8-OHdG), was
      determined in DNA isolated from 75 human breast tissue specimens and from normal
      and transformed human breast cell lines, utilising a newly developed solid-phase
      immunoslot blot assay. The amount of 8-OHdG was found to be 0.25 +/- 0.03
      pmol/microgram in normal breast tissue from reduction mammoplasty, 0.98 +/- 0.174
      pmol/microgram in benign tumours and 2.44 +/- 0.49 pmol/microgram DNA in
      malignant breast tissue with invasive ductal carcinoma. The malignant tissue had
      a statistically significant 9.76-fold higher level of 8-OHdG than normal tissue
      (P < 0.001, Mann-Whitney). A statistically significant 12.9-fold (P = 0.004)
      higher endogenous formation of 8-OHdG was also observed in cultured breast cancer
      cells compared with normal breast epithelial cells. In addition, a significantly
      elevated level (3.35-fold higher, P < 0.05) of 8-OHdG observed in oestrogen
      receptor-positive compared with oestrogen-negative malignant tissues, and in
      breast cancer cell lines (9.3-fold higher, P = 0.007) suggests a positive
      relationship between 8-OHdG formation and oestrogen responsiveness. The extent of
      8-OHdG adducts did not show a discernible correlation with either the age or the
      smoking status of the patients. These results indicate that the accumulation of 8
      OHdG in DNA has a predictive significance for breast cancer risk assessment and
      is conceivably a major contributor in the development of breast neoplasia.

PMID- 8758256
TI  - Elevated serum E-selectin in patients with liver metastases of colorectal cancer.
AB  - E-selectin, an endothelial cell adhesion molecule, mediates the initial step of
      leucocyte adhesion to activated vascular endothelium. The soluble isoform of E
      selectin promotes angiogenesis in rat cornea. In the present study, we
      investigated whether leucocyte adhesion and angiogenesis are also involved in
      tumour progression and metastasis of colorectal cancer. Therefore, we determined
      the level of circulating soluble E-selectin in serum samples of 38 patients with
      colorectal cancer; 20 patients with non-metastatic and 18 patients with
      metastatic disease. Median levels of soluble E-selectin were found to be
      significantly higher in metastatic tumour disease (88.7 ng/ml, range 25-203
      ng/ml) than in healthy controls (34.9 ng/ml, range 15-59 ng/ml, P = 0.01), in
      patients with primary tumours or with local recurrences (39.5 ng/ml, range 22-100
      ng/ml). Furthermore, there was no correlation with the serum level of C-reactive
      protein, fibrinogen or tumour necrosis factor alpha suggesting that the elevation
      of E-selectin is independent of inflammation in tumour patients. Therefore, we
      propose that elevated soluble E-selectin may reflect increased neovascularisation
      in metastatic tumour tissue.

PMID- 8758257
TI  - Azidothymidine in combination with 5-fluorouracil in human colorectal cell lines:
      in vitro synergistic cytotoxicity and DNA-induced strand-breaks.
AB  - The in vitro cytotoxicity of the combination of azidothymidine (AZT) and 5
      fluorouracil (5-FU) against the human colorectal cancer cells SW-480, SW-620 and
      COLO-320DM was evaluated. The cytotoxic effects of 5-FU and AZT were determined
      by the assay using 2,3-bis(2-methoxy-4-nitro-5-sulfophenil)-2H-tetrazolium-5
      carbo xanilide inner salt (XXT), while drug-induced DNA strand-breaks were
      measured using a fluorometric analysis of DNA unwinding. After an exposure of 72
      h, 5-FU and AZT induced a dose-dependent cytotoxicity against each cell line. The
      addition of 3, 10 and 30 microM AZT to various concentrations of 5-FU, as well as
      the addition of 0.5, 1 and 3 microns 5-FU to various concentrations of AZT,
      resulted in an enhanced cytotoxic effect. Isobologram analysis and the
      combination index (CI) method demonstrated that the interaction between 5-FU and
      AZT was clearly synergistic in each cell line, except for the 30% level of effect
      in SW-620, where borderline synergism was observed. The evaluation of DNA strand
      breaks after an exposure of 16 h to 5-FU, AZT or 5-FU + AZT demonstrated that the
      5-FU + AZT combination produced the greatest DNA damage, and that this
      interaction was synergistic in each cell line. In conclusion, our study supports
      the evidence that the potential antitumour activity of AZT can be modulated by
      combining it with agents which inhibit thymidylate (dTMP) formation, such as 5
      FU, and that the increased cytotoxicity is related to enhanced DNA damage. These
      findings should encourage further experimental and clinical studies of the
      potential use of AZT in combination with inhibitors of de novo dTMP synthesis.

PMID- 8758258
TI  - The activity and expression of thymidine phosphorylase in human solid tumours.
AB  - Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial
      cell growth factor (PD-ECGF) and has angiogenic activity. Since dThdPase seems to
      have an important role in angiogenesis of tumours, we measured the activity and
      expression of dThdPase in various tumours and the adjacent non-neoplastic
      tissues. We assayed dThdPase activity by spectrophotometric means, and the
      expression of dThdPase was examined by immunoblotting and by immunohistochemical
      staining using a monoclonal antibody against dThdPase. In the oesophagus,
      stomach, colorectum, pancreas, and lung, dThdPase activity in carcinomas was
      significantly higher (P < 0.05) than that in the adjacent non-neoplastic tissues.
      The expression level of dThdPase detected by immunoblotting correlated well with
      the activity of dThdPase. In the oesophagus, stomach, colorectum, gall bladder,
      pancreas and lung, the proportion of dThdPase-positive tumours was significantly
      higher (P < 0.05 or 0.01) than that of the dThdPase-positive adjacent normal
      tissues. In oesophageal, gastric colorectal and lung carcinomas, the proportion
      of dThdPase positivity in advanced carcinomas was significantly higher (P < 0.01)
      than that in early carcinomas. Tumour-infiltrative macrophages or lymphocytes in
      the lymph node, alveolar macrophages and Kupffer cells expressed high levels of
      dThdPase. The results indicate that dThdPase activity and expression level in
      many tumours are higher than those in the adjacent non-neoplastic tissues, and
      that dThdPase may have an important role in the proliferation of these solid
      tumours.

PMID- 8758259
TI  - Phenotypic and functional characterisation of tumour-infiltrating lymphocytes
      derived from thyroid tumours.
AB  - The natural history of thyroid tumours and the hyper-reactivity of the immune
      system in patients with thyroid cancer suggest that immune surveillance may play
      a role in the control of this disease. A study was therefore undertaken to
      analyse the phenotypic and functional features of tumour-infiltrating lymphocytes
      (TILs) derived from thyroid tumours. In a series of experiments, it was found
      that, in contrast to TILs derived from patients with melanoma or renal cell
      carcinoma, thyroid TILs could be efficiently expanded in vitro only in the
      presence of allogeneic EBV transformed B (B. EBV) cells. Indeed, only one of the
      seven thyroid-derived TILs grew in vitro without feeder cells, whereas all 16
      thyroid-derived TILs could be expanded in the presence of allogeneic B. EBV
      feeder cells. Phenotypic analysis of these TILs revealed a frequent in vitro
      expansion of an unusual T cell population that expressed both the CD4 and CD8
      markers. Indeed, it was demonstrated that in five of 14 TILs in short-term
      culture (< day 23) and four of 11 TILs in long-term culture (> day 40), a
      lymphocyte population that coexpressed CD4 and CD8 antigen accounted for more
      than 15% of the total TIL population. This double-positive T cell population was
      not observed in TILs derived from melanoma or renal cell carcinoma. Thyroid
      derived TILs also displayed an intense cytolytic activity against NK-sensitive
      tumour targets with 10 of 11 TILs exhibiting significant cytotoxicity towards the
      NK-sensitive K562 cell line. Six of 11 TILs were also cytotoxic towards
      autologous tumour, but when cold target inhibition with K562 was performed with
      three cultures, unlabelled K562 completely inhibited lysis of autologous tumour
      cells. A significant expansion of CD3+CD56+ T cells in the different TIL
      populations may explain this high level of NK-like cytotoxicity. In conclusion,
      TILs derived from thyroid tumours could be efficiently expanded in vitro under
      certain culture conditions. Different strategies must be explored to enhance
      their specific tumour autologous specificity, however, before they can be used in
      immunotherapy protocols.

PMID- 8758260
TI  - [211At]methylene blue for targeted radiotherapy of human melanoma xenografts:
      dose fractionation in the treatment of cutaneous tumours.
AB  - 3,7-(dimethylamino) phenazathionium chloride [methylene blue (MTB)] labelled with
      alpha-particle emitter astatine-211 (211At) selectively accumulates in melanoma
      cells due to an exceptionally high affinity of MTB to melanin, and proves to be a
      very effective agent in targeting radiotherapy for pigmented human melanoma grown
      in mice. This study aimed at a selection of the most advantageous [211At]MTB dose
      fractionation leading to irreversible regression of the treated lesions. Nude
      mice bearing subcutaneous human melanoma xenografts of either highly pigmented
      HX118 or poorly pigmented HX34 human melanoma were treated with [211At]MTB
      administered intravenously. The treatment was performed using three different
      schedules of [211At]MTB fractionation: a single large dose, five fractions
      delivered sequentially every 48 h and two to five fractions given with a mean
      frequency of one per week. The effectiveness of [211At]MTB treatment was assessed
      by determination of the growth rate of cutaneous tumours and length of time
      between tumour implantation and killing of moribund mice. [211At]MTB applied with
      a mean frequency of one fraction per week appeared to be the most efficient
      treatment for highly pigmented HX118 melanomas. Its effectiveness was dependent
      on [211At]MTB activity used per fraction and the size of the cutaneous tumours at
      the beginning of the treatment. A total dose of [211At]MTB seemed of less
      importance. An irreversible regression of the lesions was achieved. Poorly
      pigmented cutaneous melanoma xenografts were affected most significantly by
      [211At]MTB applied as five fractions given every 48 h. The treatment caused a
      temporary inhibition of tumour growth after which the lesions regained the
      control growth rate. These and previous results suggest that [211At]MTB could
      successfully control the growth of already formed lesions of pigmented melanoma,
      as well as prevent metastatic spread of the tumour, provided an appropriate
      fractionation regime of the radiolabelled compound is employed.

PMID- 8758261
TI  - Sensitivity of testis tumour cells to chemotherapeutic drugs: role of detoxifying
      pathways.
AB  - In contrast to most other types of cancer, metastatic testicular germ cell
      tumours (TGCT) are cured in most patients using cisplatin-based combination
      chemotherapy. The biochemical mechanisms underlying this sensitivity have not
      been defined. Drug detoxification can modulate response to chemotherapy in vivo
      and in vitro, and therefore we measured levels of glutathione (GSH), glutathione
      S-transferase (GST) and both constitutive and cisplatin- and dexamethasone
      induced levels of metallothionein (MT) in five human testis tumour cell lines.
      The levels were compared with those in five human bladder cancer cell lines and
      two cell lines with cisplatin resistance acquired in vitro. GSH levels were
      relatively low in the testis tumour cell lines, as might be expected in drug
      sensitive cells, and there was a 77-fold increase in GSH levels in the cisplatin
      resistant testis tumour cell line. GST levels were similar in the two cell types,
      while metallothionein levels were relatively high in the testis tumour cell
      lines. These data indicate that GSH may contribute to the sensitivity of TGCT to
      chemotherapy, and that GSH expression may be involved in the acquisition of
      cisplatin resistance in these tumours.

PMID- 8758263
TI  - Long-term positron emission tomography evaluation of slowly progressive gliomas.
AB  - Non-invasive positron emission tomography (PET) was performed to identify changes
      in blood flow and metabolism, specific to early stages of tumour occurrence or
      recurrence. 2 patients with slowly progressive gliomas from early to late stages
      of tumour development were analysed by serial PET measurements of circulation and
      metabolism using 15O-gas and 18F-fluorodeoxyglucose. PET revealed a persistent
      depression of oxygen metabolism, as indicated by the regional oxygen extraction
      fraction or metabolic rate of oxygen, in the regions where tumours were later
      found. Abnormal blood flow and metabolism may precede the morphological changes
      detected by computed tomography (CT) in patients with gliomas.

PMID- 8758262
TI  - Phase II trial of N-(phosphonacetyl)-L-aspartate (PALA), 5-fluorouracil and
      recombinant interferon-alpha-2b in patients with advanced gastric carcinoma.
AB  - The aspartate transcarbamoylase inhibitor, N-(phosphonacetyl)-L-aspartate (PALA),
      synergistically enhanced the cytotoxicity of a combination of 5-fluorouracil (5
      FU) and interferon-alpha (IFN) against human colon cancer cell lines in vitro. To
      test the efficacy of this combination in the clinical setting, patients with
      locally advanced or advanced gastric carcinoma were treated with the combination
      of PALA, 5-FU and IFN (PFI). Patients were required to have biopsy-proven disease
      beyond the scope of surgical resection, measurable disease, no prior
      chemotherapy, adequate bone marrow, renal and hepatic function, to be fully
      ambulatory and to have given informed consent. Drug was administered as follows:
      PALA, 250 mg/m2, 15 min i.v. infusion, days 1, 15, 22, 29, and then weekly; 5-FU,
      750 mg/m2 daily x 5 as a continuous i.v. infusion beginning day 2, then at 750
      mg/m2 days 16, 23 and 30, then weekly; IFN, 9 MU subcutaneously three times per
      week beginning day 2. There were 22 patients enrolled. The major toxicities were
      fatigue and associated neurotoxicity, with acceptable gastrointestinal and
      haematological toxicities. There was one complete responder (5%) and 3 partial
      responders (14%); two of these responses were durable (> 3 years). Despite this
      modest clinical activity, other regimens for advanced gastric cancer such as
      FAMTX and ELF appear to have greater activity with comparable toxicity.

PMID- 8758264
TI  - Bronchioloalveolar carcinoma presenting aerogenous metastasis to the upper
      airway.

PMID- 8758265
TI  - Thyroglobulin measurement and postablative iodine-131 total body scan after total
      thyroidectomy for differentiated thyroid carcinoma in patients with no evidence
      of disease.

PMID- 8758267
TI  - [Raise the level of research on infection in immunocompromised host].

PMID- 8758266
TI  - Increasing the dose intensity of chemotherapy by means of granulocyte-colony
      stimulating factor (G-CSF) support in the treatment of small cell lung cancer
      (SCLC)

PMID- 8758268
TI  - [The role of TNF alpha, IL-1 beta and MIP-1 alpha in LPS-induced organ injury].
AB  - OBJECTIVE: To investigate the role of inflammatory cytokines in endotoxemia
      models and to explore the possible anti-cytokine therapy of endotoxemia. METHODS:
      TNF alpha in plasma was measured by ELISA, and the mRNA of cytokines was assessed
      by slot blot analysis. RESULTS: LPS-induced TNF alpha release was in a
      dose:dependent manner in human whole blood. Dexamethasone (> or = 10(-8)mol/L)
      exhibited inhibitory effect on TNFa release. Ibuprofen 10(-7)-10(-9) mol/L had
      inhibitory effect on TNFa production, whereas 10(-3)-10(-4)mol/L stimulated TNFa
      release. The rat model of acute lung injury was made by LPS intraperitoneal
      injection. Both dexamethasone and ibuprofen that injected at 1 hour before LPS
      injection could decrease the contents of Evans blue in the lung (t 2.80 and 7.31
      respectively, P < 0.05 vs LPS control). After LPS administered, there was a
      progressive up regulation in transcripts of TNF alpha, IL-1 beta and MIP-1 alpha
      in whole lung homogenates of rats. The mRNA peaked at 2, 6, 12 hours
      respectively. The TNF alpha, IL-1 beta and MIP-1 alpha mRNA levels decreased
      markedly when dexamethasone or ibuprofen given at 1 hour before LPS injection.
      CONCLUSION: TNF alpha, IL-1 beta and MIP-1 alpha play an essential role in the
      inflammatory response. LPS-induced acute lung injury may be prevented by
      dexamethasone and ibuprofen which have inhibitory effect on the gene expression
      of cytokines in the lung.

PMID- 8758269
TI  - [The effect of cytokines on the liver necrosis].
AB  - OBJECTIVE: To investigate the effect of cytokines on liver necrosis. METHODS: We
      injected IL-1, IL-6, IFN gamma, TNF alpha with or without D-galactosamine (D-GAL)
      into the abdominal cavity of mice separately. RESULTS: There was no effect on
      hepatocyte of normal mice after injection of IL-1, IL-6, IFN gamma alone or
      together. The serum total bilirubin (TBIL) and liver necrosis of mice increased
      more markedly by using of TNF alpha, IL-6 or IFN gamma separately with D-GAL
      (TBIL: 46.2 +/- 10.6 micromol/L, 44.6 +/- 12.9 micromol/L, 41.9 +/- 14.9
      micromol/L), then by D-GAL alone (TBIL: 27 +/- 11 micromol/L) also the serum TBIL
      of mice and liver necrosis also increased after injection of IL-1, IL-6 with D
      GAL and TNF alpha. CONCLUSION: Cytokines like IL-1, IL-6, IFN gamma and TNF alpha
      joined the process of hepatocyte necrosis. They can enhance the degree of liver
      necrosis induced by D-GAL.

PMID- 8758270
TI  - [Nosocomial bacterial infection in comprehensive intensive care unit].
AB  - OBJECTIVE: To establish the prevalence of nosocomial bacterial infection and
      changes in resistance in a comprehensive intensive care unit. METHODS: We
      retrospectively analyzed all the bacterial isolates of ICU, PUMC Hospital from
      1989 to 1994, such as the species and resistance pattern. RESULTS: Among all
      bacterial isolates, the percentage of Gram-positive cocci steadily increased (16%
      in 1989, 33% in 1994), while that of Gram-negative bacilli decreased (84% in
      1989, 67% in 1994). The most prevalent isolates of Gram-negative pathogens were
      Pseudomonas aeruginosa, Acinetobacter baumanii, inducible Enterobacteriaceae and
      Xanthomonas maltophilia, with imipenem and amikacin as the most susceptible
      antibiotics. Enterococci, oxacillin-resistant Staphylococcus epidermidis and
      oxacillin-resistant Staphylococcus aureus accounted for 44%, 21% and 10%,
      respectively. The resistant rate of these three Gram-positive bacteria to
      vancomycin were 19%, 0% and 0%. CONCLUSION: Understanding of the epidemiological
      data and changes of bacterial resistance profile is prerequisite to rational use
      of antibiotics, which is crucial to reducing the resistance of nosocomial
      infection pathogens.

PMID- 8758271
TI  - [Liver transplantation report of 23 cases].
AB  - OBJECTIVE: To explore the experience of liver transplantation in patients with
      terminal liver failure. METHOD: From October 1991 to July 1995, 17 adults and 6
      children underwent orthotopic liver transplantation. Preoperative diagnosis
      showed biliary atresia (n = 5), Alagille syndrome (n = 1), primary biliary
      cirrhosis (n = 2), cryptogenic cirrhosis (n = 2), alcoholic cirrhosis (n = 4),
      Wilson's disease (n = 1), fulminant hepatic failure (n = 3), polycystic liver (n
      = 2), secondary biliary cirrhosis (n = 1), hepatitis B cirrhosis (n = 1), and
      autoimmune hepatitis associated with a small hepatocellular carcinoma (n = 1).
      One paediatric patient suffered from hepatitis of unknown aetiology which
      progressed to liver failure after liver transplantation. She received
      retransplantation using a living graft from her mother. The liver grafts were
      obtained from 17 brainstem dead donors and 7 living donors. RESULTS: The overall
      patient survival rate was 92% and graft survival rate was 88%. There were only 2
      deaths, one was due to primary graft nonfunction and the other was due to
      persistent graft rejection not responding to pulse steroid and OKT3. The other
      patients are alive and well. CONCLUSIONS: Liver transplantation is a feasible and
      viable treatment for patients with terminal liver failure in Hong Kong. The only
      limitation is lack of brainstem dead donor. Promotion of concept of brainstem
      death and organ donation in the society is the key to wide use of liver
      transplantation for patients with terminal liver failure in Asia.

PMID- 8758272
TI  - [Application of radiolabeled anti-HBx monoclonal antibody for HCC targeting
      therapy].
AB  - OBJECTIVE: To explore the possibility of anti-HBx McAb as a carrier of HCC
      targeting therapy after we prepared successfully the anti-HBx monoclonal antibody
      by immunizing BALB/C mice with 17KD hepatitis B virus X protein. METHODS: The
      antibody was prepared, purified, identified, radiolabled and used in nude mice
      bearing human HCC and two HCC patients respectively for experimental and clinical
      trials. In the experimental study, 0.5mCi 131I-anti-HBx was injected
      peritoneally. In the clinical trial, the patients were treated with 131I-anti-HBx
      by injecting into the hepatic artery. After the treatment for one course, a total
      dose of 37.5 mCi was administered. RESULTS: The survival periods of the mice were
      prolonged and the tumors were suppressed significantly. The symptoms of the
      patients were improved significantly with decreased titre of AFP. The B
      ultrasonic and CT scanning showed that the tumors became smaller. For these
      reasons, one of the two patients was reoperated. The tumor was removed and
      necrosis of the whole tumor was noted except few living tumor cells on the edge
      of tumor specimen. CONCLUSIONS: It is possible to use the anti-HBx monoclonal
      antibody as a carrier for human HCC targeting therapy.

PMID- 8758273
TI  - [C-myc activation by translocation in human primary non-small cell lung cancer].
AB  - OBJECTIVE: Lung cancer is one of the most common human neoplasms. The
      carcinogenesis and development of lung cancer are related to activation and
      inactivation of many oncogenes and tumor-suppressor genes. We reported c-myc
      activation by translocation in SV40T-transformed human bronchial epithelial cells
      and lung cancer cell line before. In order to confirm that c-myc translocation
      exists in human primary non-small cell lung cancer, we continued our studies in
      12 primary human lung cancers. METHODS: We applied major fluorescence in situ
      hybridization (FISH) in combination with immunohistochemistry. RESULTS: c-myc
      translocation was detected in two cases of the 12 primary lung cancers.
      Overexpression of c-myc was detected in the two cases by means of
      immunohistochemistry. CONCLUSION: These results suggest that c-myc can be
      activated by translocation in human primary lung cancer.

PMID- 8758274
TI  - [The inhibitory effects of serum of patients with acute promyelocytic leukemia on
      the formation of megakaryocytopoiesis colony unit].
AB  - OBJECTIVES: To determine if the sera of patients with acute promyelocytic
      leukemia (APL) and all-trans retinoic acid (ATRA) inhibit the formation of colony
      forming-unit of megakaryocyte (CFU-Meg). METHODS: By cellular culture assay, the
      sera of 22 APL patients treated with ATRA and 10(-6)' mol/L ATRA were kinetically
      used to perform the investigation. Meanwhile, serum tumor necrosis factor (TNF)
      activity and bone marrow CFU-L were also detected. RESULTS: Before treatment,
      there was an inhibitory activity on CFU-Meg in the serum of APL patients (29.6%
      +/- 2.4%). The activity reduced gradually with the treatment and was stimulus
      when bone marrow remission obtained (-18.7% +/- 4.1%, P < 0.001). It was
      positively correlated with TNF activity in the serum and the number of CFU-L
      however negatively correlated with the number of megakaryocyte in bone marrow and
      PLT. Serum TNF activity and the number of CFU-L before treatment were higher than
      those after treatment (P < 0.05 and < 0.001, respectively). ATRA could stimulate
      the growth of CFU-Meg. CONCLUSIONS: There was an inhibitory activity in the serum
      of APL patients which could be used to monitor the efficacy of the therapy. ATRA
      stimulates the growth of CFU-Meg.

PMID- 8758275
TI  - [Expression of epidermal growth factor receptor (EGFR) in endometrioid carcinoma
      of the ovary].
AB  - OBJECTIVE: To determine the expression of EGFR expression in endometrioid
      carcinoma of the ovary and its relationship to clinicopathologic features and
      prognosis. METHODS: Expression of EGFR oncoprotein was studied by
      immunohistochemistry in paraffin-embedded tumor tissues from 28 patients with
      endometrioid carcinoma of the ovary. RESULTS: Tissues from 13 patients (46.4%)
      were stained positively with EGFR polyclonal antibody (1005). The staining was
      membranous and/or cytoplasmic. There was no relationship between EGFR expression
      and age at diagnosis, preoperative CA125 titer, clinical stage, histologic grade,
      and lymph node metastases. A higher expression rate was observed in patients with
      residual tumors (56.3% versus 33.3%). The mortality rate was higher in patients
      with EGFR expression than in those without EGFR expression (46.2% versus 14.3%),
      but the difference was not statistically significant. CONCLUSION: EGFR expression
      was not related to the clinicopathologic features in endometrioid carcinoma of
      the ovary, but was related to the poor prognosis of this disease.

PMID- 8758276
TI  - [Detection of bacterial vaginosis in gram stained vaginal smears and papanicolaou
      stained cervical smears].
AB  - OBJECTIVE: To determine the sensitivity and specificity of diagnosis of bacterial
      vaginosis (BV) by papanicolaou (PAP)-stained cervical smears and gram-stained
      vaginal smears according to clinical criteria. METHODS: In the prospective study
      of 196 non-pregnant women of child-bearing age, 94 were clinically diagnosed to
      have BV. Gram-stained vaginal smears and PAP-stained cervical smears were
      collected from all enrolled patients. RESULTS: In comparison with clinical
      diagnosis of BV, the sensitivity and specificity of gram-stained vaginal smears
      and PAP-stained cervical smears were 94.7% (89/94), 98.0% (100/102) 85.1%
      (80/94), and 95.1% (97/102). The characteristics of BV in gram-stained vaginal
      smears and PAP-stained cervical smears included small bacteria of Gardnerella and
      bacteroides morphotypes and curved gram variable rods and absence of bacteria of
      Lactobacillus morphotypes. CONCLUSION: It is possible to screen and manage BV
      according to Gram-stained vaginal smears or PAP-stained cervical smears.

PMID- 8758277
TI  - [Correlation analysis of the changes of EEG mapping and the changes of CT scan in
      patients with senile dementia].
AB  - OBJECTIVE: To observe the changes of EEG mapping and CT scan and analyse the
      correlation between the changes of the function presented by EEG mapping and
      morphology presented by CT. METHODS: The absolute power of EEG mapping and 9
      parameters of CT in 30 normal controls and 31 patients with senile dementia were
      measured. The correlation was analysed quantitatively with multiple stepwise
      regression method. RESULTS: The EEG mapping of senile dementia revealed a diffuse
      increase in delta, theta power and decreased alpha power in most areas. CT scan
      showed cortical and subcortical atrophy in brain. There were positive
      correlations between the increase of delta power and lateral fissure, and between
      the increase of delta power and average cerebral sulcus. There was a negative
      correlation between the decrease of alpha power and the increase of lateral
      fissure. CONCLUSION: The EEG mapping and CT in patients with senile dementia are
      different from those in normal elderly. There is a correlation between the
      changes of EEG mapping and CT scan.

PMID- 8758278
TI  - [Receptor mechanism of dynorphin A in rat secondary spinal cord injuries].
AB  - OBJECTIVE: To clarify the effects of dynorphin A on secondary spinal cord
      injuries. METHODS: Spinal cord injured rat model made according to modified
      Allen's method was used by comparing the effect of intrathecal dynorphin A
      antiserum and that of its receptor antagonist nor-BNI. RESULTS: The recovery of
      the muscle tension and motor function of the hindlimb in dynorphin antiserum
      group was markedly faster than that in both control and nor-BNI groups. Also, the
      recovery of motor function in the nor-BNI group was favorable at the early stage
      of injury, compared to the control group. Pathological observation showed that
      the residual area of the spinal cord in dynorphin A1-13 antiserum group was
      larger than that in both control and nor-BNI groups. The residual area of the
      spinal cord in the nor-BNI group was also larger than that in the control group.
      CONCLUSION: These observations support the hypothesis that dynorphin contributes
      to certain pathophysiological changes following traumatic SCI through both opiate
      receptor mediated and nonopioid mechanisms.

PMID- 8758279
TI  - [Dynamic changes of amino acids in extracellular fluid in rat hippocampus in
      cases of cerebral ischemia].
AB  - OBJECTIVE: To study the changes of excitatory amino acid (EAA) in patients with
      cerebral ischemia. METHODS: We observed dynamic changes of EAA in extracellular
      fluid by intracerebral microdialysis inserted in hippocampus through stereotaxic
      method with modified Pulsinelli's model of four vessels occlusion. RESULTS: The
      concentration of Glu was 5.88 +/- 1.40 and 11.2 +/- 1.5 micromol/L in patients
      with incomplete cerebral ischemia after 30 minutes and 60 minutes, and the
      concentration of Asp was 2.72 +/- 0.24 and 4.4 +/- 0.6 micromol/L. The
      concentration of Glu was 15.1 +/- 1.6 micromol/L and 17.9 +/- 1.6 micromol/L in
      patients with complete cerebral ischemia after 30 minutes and 60 minutes, and the
      concentration of Asp was 8.2 +/- 1.0 and 12.1 +/- 1.1 micromol/L. The
      concentration of Glu and Asp was 1.75 +/- 0.88 micromol/L and 0.24 +/- 0.09
      micromol/L in the controls. CONCLUSIONS: In this study, the concentration of Glu
      and Asp in patients with cerebral ischemia was significantly increased than in
      the controls, and the more serious ischemia was, the more release of EAA. It is
      suggested that Dansen injection can reduce the release of EAA by cerebral cells
      in case of ischemia.

PMID- 8758280
TI  - [The disturbance of calcium homeostasis in vascular smooth muscle proliferation
      after balloon denudation].
AB  - OBJECTIVE: To investigate the changes of calcium homeostasis in smooth muscle
      cells (VSMC) and the role of disturbance of calcium homeostasis in VSMC
      proliferation after balloon denudation. METHODS: Assay of the cellular
      incorporation of 3H-leucine and measurement of 45Ca transport were done on the
      model of balloon-denuded aorta in rat. RESULTS: Endothelial injury induced VSMC
      proliferation, intimal thickening. After balloon denudation, VSMC calcium influx
      increased (3 days after balloon denudation, 3.28 +/- 0.14 vs 4.12 +/- 0.28, P <
      0.05; 10 days 3.31 +/- 0.09 vs 4.09 +/- 0.21 nmol/10(6) cells, P < 0.01), and
      calcium efflux decreased, and calcium content increased (3 days after balloon
      denudation 695 +/- 33 vs 995 +/- 54, P < 0.01; 10 days 709 +/- 32 vs 1022 +/- 94
      nmol/10(6) cell, P < 0.01). SR and mitochondria calcium uptake increased. Calcium
      antagonist, verapamil not only regulated the disturbance of calcium homeostasis,
      but also inhibited endothelium injury-induced VSMC proliferation. CONCLUSION: The
      disturbance of calcium homeostasis is probably one of the underlying mechanisms
      of VSMC proliferation induced by balloon denudation.

PMID- 8758281
TI  - [Osteoblast-like cells cultured in vitro].
AB  - OBJECTIVE: To identify the relationship of osteogenesis and osteoblast-like cells
      from different tissues, and the shape and functional changes of these cells in
      their different growing stages. METHODS: Three types of osteoblast-like cells,
      long spindle-shaped, spherical, and squamous cells were obtained from the fetal
      calvaria of SD rats or Leghorn chickens cultured in vitro. RESULTS: The long
      spindle-shaped and the spherical cells developed into the squamous cells. They
      had the same developing tendency and the same results of development. Three types
      of cells in their different growing stages displayed separately their functional
      status. They secreted acid mucopolysaccharide, collagen, calcium salt, alkaline
      phosphatase, etc. The secreted substances heaped up to form new bone tissues. At
      the same time there were positive acid phosphatase-staining cells around the new
      bone tissues. CONCLUSIONS: The cells isolated from the fetal calvaria contained
      two lines of bone cells, carrying out both bone formation and bone resorption.

PMID- 8758283
TI  - [Application and development of immunity of childhood vaccines].

PMID- 8758282
TI  - [Assignment of differentiation-relevant cDNA RA538 on human chromosomes by
      fluorescence in situ hybridization].
AB  - OBJECTIVE: To localize the differentiation-relevant cDNA RA538 (3.8kb) onto the
      human chromosome 8q2. METHODS: A modified non-isotopic labeling technique was
      used. RESULTS: The cDNA RA538 was obtained by subtraction hybridization from
      human esophageal cancer cell line EC8712 induced by retinoic acid. Fluorescence
      in situ hybridization (FISH) using double-labeled probes showed clear and paired
      hybridization signals at the corresponding regions of both two chromatids in 18
      out of 60 metaphases examined. While by single-labeling, only 7 were positive in
      60 metaphases observed and the fluorescent spots were seen only at one chromatid.
      CONCLUSION: The modified FISH protocol is useful for mapping cDNA sequences of a
      few kilobases.

PMID- 8758284
TI  - Control of parasitic diseases in China. Current status and prospects.

PMID- 8758285
TI  - Experimental and field studies on some biological characteristics of Plasmodium
      vivax isolated from tropical and temperate zones of China.
AB  - OBJECTIVE: To clarify some biological behaviors of Plasmodium vivax including the
      periodical infectivity of gametocytes for mosquitoes, the prepatent period, the
      incubation period, the relapse patterns and their relationship. METHODS:
      Laboratory reared Anopheles sinensis were fed through fetal membrane on blood
      from patients naturally infected with vivax malaria. After feeding at different
      hours, the engorged mosquitoes kept in the insectarium were dissected 5-7 days
      later. The percentage of mosquitoes infected and the mean number of oocysts per
      gut were taken as criteria of the viability of the gametocytes. The healthy
      volunteers artificially infected by mosquito bite or quantitative inoculation of
      sporozoites were treated with 1.5 g chloroquine base alone before and after the
      first and subsequent onset of fever to detect the natural course of disease in
      human body. RESULTS: The infection in mosquitoes can readily be divided into
      upward, peak, downward and non-infective period. The infectivity reached a peak
      at interschizogony period and fell to low level at the time when schizogony
      occurred. The short incubation period was frequently observed in persons bitten
      by 10 infected mosquitoes or 10 000 sporozoites inoculated and the long
      incubation period was constantly recorded in cases receiving 100 sporozoites.
      When one mosquito was allowed to feed on volunteers or 1 000 sporozoites were
      injected, the incubation period may be short or prolonged. CONCLUSIONS: The 48
      hour cycle in the infectivity of gametocyte for mosquitoes was demonstrated and
      the peak of oocyst production preceded the peak of parasitaemia by 1 to 3 days.
      Prompt radical treatment is extra important. Since the incubation period is
      variable depending on the number of sporozoites inoculated and the tropical
      versus temperate zone malaria is not all-inclusive, the classification of tertian
      malaria might be reconsidered.

PMID- 8758286
TI  - Field studies on the preventive effect of oral artemether against schistosomal
      infection.
AB  - OBJECTIVE: To study the preventive effect of oral artemether (Art) against
      schistosomal infection in the field. METHODS: In Minglang District of Yiyang
      City, Hunan Province, there is an islet with embankment type endemic area in the
      southern Dongting Lake region. From August to October 1994 the residents who
      frequently contacted the infested water were selected for study and allocated to
      the Art group and the control group. About one month before the preventive Art
      administration, all the residents understudied were examined by stool hatching
      technique, and then treated orally with praziquantel at a single dose of 40 mg/kg
      in stool egg-negative residents and 50 mg/kg in stool egg-positive ones. In the
      Art group, the first dose of 6 mg/kg was given at the end of August, followed by
      3 repeated doses every 15 days. Placebo (starch) was given to the control group
      at the same time as in the Art group. The preventive efficacy was evaluated by
      stool examination 25-32 days after the last medication. RESULTS: In the Art
      group, 20 out of 365 studied residents became stool positive with an infection
      rate of 5.5%, while in the control group, 51 out of 376 studied residents were
      stool positive with an infection rate of 13.6%. The egg count per gram of feces
      (EPG) determined by the Kato-Katz method was 122 +/- 79 in the Art group and 681
      +/- 909 in the control group. Meanwhile, two cases of acute schistosomiasis were
      found in the control group, but none was observed in the Art group. No apparent
      adverse side effect was seen during the treatment with Art. CONCLUSION: Oral Art
      exhibited apparent preventive effect on the residents who contacted the infested
      water in schistosomiasis endemic area.

PMID- 8758287
TI  - Serotype epidemiology and patterns of antibiotic susceptibilities of salmonellae
      isolated in Hong Kong 1983-93.
AB  - OBJECTIVE: To study the serotype epidemiology and patterns of antibiotic
      susceptibilities of salmonellae isolated in Hong Kong over an eleven-year period.
      METHODS: The laboratory information of 22 733 strains of salmonellae isolated
      from diarrhea stool samples of 7 public hospitals, 5 out-patient clinics and 2
      public health laboratories and reported to the Salmonella surveillance system in
      Hong Kong from 1983 to 1993 were analysed. RESULTS: The yearly total number of
      isolates has remained steady, while an increasing proportion of cases occurred in
      the > 25 years age group with a substantial decline in the < 1 age group. Males
      were significantly more affected than females, particularly in those < 15 years
      old. S. typhimurium and S. derby were the two most commonly isolated serotypes
      throughout the period. An outbreak of S. portsmouth occurred which accounted for
      15.3% of total isolates in that year. S. enteritidis has doubled in the last 2
      years, while S. typhi has more than halved over the 11-year period. The S.
      enteritidis increase was seen mostly in the > 25 age groups, with those < 5 years
      little affected. Antibiotic susceptibility tests showed the typhoid and
      paratyphoid bacilli remained fully antibiotic sensitive, while non-typhoid non
      paratyphoid isolates showed increasing resistance to ampicillin, chloramphenicol,
      tetracycline, and cotrimoxazole. CONCLUSIONS: Laboratory monitoring of salmonella
      serotypes causing diarrhea and their antibiotic susceptibilities is essential as
      population movements and industrial activities increase in the southern parts of
      China.

PMID- 8758288
TI  - Interrelationship between magnesium and potassium in preventing myocardial
      ischemia-reperfusion arrhythmia.
AB  - OBJECTIVE: To assess the interrelationship between Mg2+ and K+ in preventing
      reperfusion arrhythmia (RA). MATERIAL AND METHODS: 72 rat hearts were randomly
      divided into 6 equal groups, and perfused with various combinations of Mg2+ and
      K+ in the perfusate by Langendorff method. Each heart was subjected to coronary
      occlusion for 15 minutes followed by 12-minute reperfusion. The incidence of RA
      was recorded. The concentration of K+ and malondialdehyde (MDA) in the coronary
      effluent before and after reperfusion were measured with increasing
      concentrations of Mg2+ and fixed concentration of K+. RESULTS: All forms of
      ventricular arrhythmias occurred after reperfusion but with decreased incidence
      by increasing Mg2+ and K+. When both Mg2+ and K+ were in high level, no VF
      appeared on reperfusion. However, when they were both in low level, 100% of
      hearts developed severe arrhythmia. The concentration of K+ and MDA in the
      coronary effluent was markedly increased compared with that before reperfusion,
      and the loss of K+ and malondialdehyde (MDA) decreased with increasing Mg2+.
      CONCLUSIONS: Mg2+ may prevent or reduce the incidence of RA by maintaining the
      integrity of intracellular K+ and by reducing the lipid peroxide reaction.

PMID- 8758289
TI  - Cervical cancer screening in an urban population in Taiwan: five-year results.
AB  - OBJECTIVE: To review the first five years of the educational and cervical cancer
      screening program (ECCSP) at twelve public health centers in the metropolitan
      area of Taipei and to measure whether the ECCSP had an impact on cancer patterns.
      METHODS: We used data for cervical cancers diagnosed between 1986 and 1991 from
      all hospitals in Taipei and from the national cancer registry. During this time
      period, 2 158 cervical cancers were diagnosed from thirty-nine hospitals in
      Taipei city, of which 5% were identified after referral from the ECCSP: RESULTS:
      The percentage of early cervical cancers, defined as stage 0 or Ia, was 70% in
      women referred from the ECCSP, compared with 20% for women who were not referred
      from the ECCSP (P < 0.001). All age groupings also demonstrated this similar
      difference. The case-fatality rate of cervical cancer was significantly lower for
      ECCSP referred patients (8 of 106, 7.5%) than for non-ECCSP referred patients
      (401 of 2 051, 19.6%) during this study period (P < 0.01). CONCLUSIONS: This
      information suggests that the ECCSP has had a remarkable impact on the early
      diagnosis of cervical cancer. It is expected that a well organized screening
      program will be applied to a large target population from young to old adults so
      that the program can be effective for reducing the mortality rate of cervical
      cancer in Taiwan.

PMID- 8758290
TI  - Cordocentesis: a useful method for prenatal diagnosis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of cordocentesis for prenatal
      diagnosis of various fetal diseases. PATIENTS AND METHODS: Fetal blood sampling
      was performed in 30 pregnancies from gestational week 19 to 36 for various
      prenatal diagnoses. We used Aloka SSD-650 real-time ultrasound scanner with 3.5
      mHz curvilinear transducer during the procedure. A regular 22-gauge spinal needle
      was used for fetal blood sampling. RESULTS: Twenty-five cordocentesis were
      successful at the first attempt. A second attempt of cordocentesis succeeded in
      three cases. In the remaining two cases, intrahepatic vein sampling and
      cardiocentesis were employed respectively. The duration of procedure was shorter
      than 15 minutes in 25 cases. 1-6 ml of fetal blood was obtained from each case.
      Fetal blood was diluted with amniotic fluid in four samples. Maternal blood
      contamination never happened. No lethal complication occurred in our series.
      CONCLUSION: It is believed that cordocentesis is a safe and useful method for
      prenatal diagnosis, and intrahepatic vein sampling is an alternative choice when
      cordocentesis has failed.

PMID- 8758291
TI  - Detection of PML-RAR alpha in patients with APL during follow-up period.
AB  - OBJECTIVE: To evaluate the significance of PML-RAR alpha transcripts in patients
      with acute promyelocytic leukemia (APL) during remission period and to follow up
      the patients through monitoring aberrant gene expression. PATIENTS AND METHODS:
      This study included 17 patients with APL (5 females and 12 males). Another 19 APL
      patients during relapse served as control. RNA extraction was obtained through
      the single-step method. By means of reverse transcriptase polymerase chain
      reaction (PCR), the PML-RAR alpha was detected in the sample mRNA. RESULTS: Nine
      out of 10 patients with complete remission (CR) duration shorter than 3 years
      were positive. Four cases became negative and three remained positive among 7
      cases in a long remission of over 3 years. The difference of the positive rate of
      PML-RAR alpha transcripts between the 2 groups was significant (P < 0.05). Four
      among 12 positive cases relapsed. No evidence of relapse was present in the 5
      negative patients after 9.6 +/- 3.9-month follow-up. Further treatment was
      therefore given to the 4 positive patients whose treatment was already ceased at
      that time. By this management they were all in CR during the following 10-month
      observation. CONCLUSIONS: RT-PCR detection for PML-RAR alpha transcripts was
      useful in monitoring MRD and guiding further treatment to obtain a long
      remission. Persistently positive transcripts were closely associated with the
      relapse.

PMID- 8758292
TI  - Different methylation patterns of the M-BCR gene in myeloblastic and
      lymphoblastic crisis of chronic myelocytic leukemia.
AB  - OBJECTIVE: To investigate the relationship between methylation status of M-bcr
      gene and transformation of chronic myelocytic leukemia (CML) from chronic to
      blastic phase. MATERIAL AND METHODS: The methylation patterns of M-bcr in 23
      patients with Ph' positive CML were studied. DNAs extracted from mononuclear
      cells of both chronic and blastic phases (20 cases) or blastic phases only (3
      cases), were doubly digested with restriction enzymes HpaII and BglII, hybridized
      with a 5'M-bcr probe labeled with 32p-deoxycytidine triphosphate, and
      autoradiographed. RESULTS: In all the patients with myeloblastic crisis, DNAs
      from both chronic and blastic cells of each patient showed identical methylation
      patterns. There was substantial heterogeneity in methylation patterns in the
      patients with lymphoblastic crisis. All the lymphoblastic patterns were distinct
      from the chronic patterns as well as the patterns shown in myeloblastic crisis.
      Moreover, in four out of six patients with lymphoblastic crisis, the chronic
      patterns were different from those in cases with myeloblastic crisis.
      CONCLUSIONS: The methylation status of M-bcr was stable during evolution of CML
      from chronic to myeloblastic phase. Analysis of M-bcr methylation status may be
      of clinical use in distinguishing lymphoblastic from myeloblastic crisis and
      predicting the cell lineage of crisis when the disease is still in its chronic
      phase.

PMID- 8758293
TI  - The combination of melphalan, cyclophosphamide and cytosine arabinoside as a
      conditioning regimen for autologous bone marrow transplantation for acute
      leukemia.
AB  - OBJECTIVE: To explore more effective and less toxic conditioning regimen without
      total body irradiation for autologous bone marrow transplantation (ABMT) for
      acute leukemia (AL). MATERIAL AND METHODS: Twenty patients with AL were treated
      with ABMT, including 13 cases of acute myelocytic leukemia (AML) and 7 cases of
      acute lymphocytic leukemia (ALL). A median of 1.06 (range, 0.69-1.75) x 10(8)
      nucleated BM cells/kg was harvested and stored in normal salt solution containing
      heparin at 4 degrees C. The conditioning regimen (MAC) consisted of high-dose
      melphalan (M, 140-160 mg/m2), cyclophosphamide (CY, 120 mg/kg) and cytosine
      arabinoside (Ara-C, 2.0 g/m2). These 3 drugs were administered within 25 hours
      and the unpurged autologous marrow infusion began after another 24-hour interval.
      RESULTS: MAC regimen could result in myeloblastic efficacy in a week. All marrow
      cells were reinfused within 56 hours after the harvest so that hemopoietic
      reconstitutions could occur in all the patients. The median time to reach a
      neutrophil count of > 1.0 x 10(9)/L and a platelet count of > 50 x 10(9)/L was 20
      and 26 days respectively. With a median observation period of 25 months, the
      median duration on continuous complete remission in our patients was 22 months,
      and the longest reached 56 months. The median survival was 33 months, and the
      longest was over 6 years. The event-free survival at 2 years had reached 72%. In
      seven patients with leukemic relapse, six (86%) relapsed within 8 months after
      ABMT. The relapse rate and mortality in AML patients were significantly lower
      than those in ALL patients. In 7 patients with M3, relapse had not yet been
      observed. The nonhematologic toxic effects of MAC conditioning regimen occurred
      mainly in the gastrointestinal tract. CONCLUSIONS: The preliminary results
      indicated that the ABMT using MAC conditioning regimen had some advantages in
      stronger antileukemic efficacy, less extrahematologic toxicity and earlier
      recovery of platelet and could greatly prolong the duration of remission and
      survival in some patients with AL.

PMID- 8758294
TI  - Blink reflex: normal values and its findings on peripheral facial paralysis.
AB  - OBJECTIVE: To establish the normal values of blink reflex (BR) in healthy
      subjects and investigate the manifestations of BR in patients with peripheral
      facial paralysis (PFP). METHODS: BR was investigated in 23 patients with PFP and
      50 healthy persons serving as control. While stimulating the supraorbital nerve
      on one side, the reflex responses of bilateral inferior-orbicularis oculi were
      recorded respectively, in which the two components recorded on the ipsilateral
      side of stimulation were named R1, R2 and the contralateral one, R2'. RESULTS:
      There was no significant difference between sexes, sides and among various groups
      of age R1, R2 and R2'. The mean latency of R1 was 10 msec and R2, R2', 29 msec.
      The absolute values of the amplitude were of relatively smaller significance due
      to their great variance, whereas the amplitude ratio between two sides was of
      some value. All patients showed absent response, delayed latency or/and abnormal
      amplitude on the paretic side, regardless of the side of stimulation, indicating
      a typically efferent involvement. CONCLUSION: BR is another objective and
      noninvasive test for facial paralysis in evaluating the lesion site, scope and
      the abnormality degree, and predicting the prognosis if combined with the
      clinical conditions.

PMID- 8758295
TI  - Ankylosing spondylitis and heterogeneity of HLA-B27 in Chinese.
AB  - OBJECTIVE: To examine the relationship between ankylosing spondylitis and
      heterogeneity of HLA-B27 in Chinese. PATIENTS AND METHODS: We subtyped HLA-B27 in
      76 patients with ankylosing spondylitis and 1 200 healthy Chinese of Han
      nationality. Polymerase chain reaction was designed to amplify specific regions
      of class I (exon 2 and 3). Amplified sequences were tested with eight sequence
      specific oligonucleotides to distinguish all HLA-B27 subtypes. RESULTS: The HLA
      B27 was closely related to ankylosing spondylitis and at least four subtypes
      presented in Chinese patients. B2704 was the most common subtype, occurring in
      54.8% and 50.85% respectively in HLA-B27 positive ankylosing spondylitis patients
      and healthy controls. The main HLA-B27 subtypes in the HLA-B27 positive patients
      distributed in similar proportion to those of HLA-B27 positive healthy controls
      (P < 0.1). CONCLUSIONS: The prevalences of various subtypes of HLA-B27 vary in
      different races. HLA-B2704 is the main subtype in Chinese Han nationality. The
      HLA-B27 specific residues that are shared by the subtypes might be involved in
      the pathogenesis of ankylosing spondylitis.

PMID- 8758296
TI  - Spinal dorsal ramus syndrome.

PMID- 8758297
TI  - Dredging psychotherapy: its relationship with traditional Chinese culture and
      ancient Chinese medicine.

PMID- 8758298
TI  - Correlation between brain edema on CT-scan and fine structure changes in patients
      with intracranial tumors.

PMID- 8758299
TI  - Detection of unstable coronary atherosclerotic lesions by intracoronary
      ultrasound.

PMID- 8758300
TI  - Primary malignant pheochromocytoma in the left forearm.

PMID- 8758301
TI  - Leiomyomatosis peritonealis disseminata. Two case reports.

PMID- 8758302
TI  - Differentiation therapy of acute promyelocytic leukemia.

PMID- 8758303
TI  - Recent study on colorectal cancer in China.

PMID- 8758304
TI  - A concept in analgesic mechanisms of acupuncture.

PMID- 8758305
TI  - In situ molecular biological techniques.

PMID- 8758306
TI  - Improve the DNA recombination protein drugs.

PMID- 8758307
TI  - Cardiac cytotoxic mechanism mediated by antibodies against myocardial
      mitochondrial ADP/ATP carrier in patients with dilated cardiomyopathy.
AB  - OBJECTIVE: To investigate mechanism of the antibody-mediated cardiac cytotoxicity
      and clinical significance in dilated cardiomyopathy (DCM), and study the effects
      of the antibodies against the myocardial mitochondrial ADP / ATP carrier from
      sera of patients with dilated cardiomyopathy on the guinea pig ventricular
      myocytes. PATIENTS AND METHODS: This study included 18 patients with DCM (12 men
      and 6 women), with mean age of 43 years. Control group included 18 health donors,
      (9 men and 9 women), with mean age of 32 years. The antibodies against the ADP /
      ATP carrier and cell membrane 52 000 peptide were examined by immunoblotting. The
      antibody-mediated cardiac cytotoxicity was studied with the cytotoxic test and
      whole cell patch-clamp technique. RESULTS: The antibodies against myocardial
      mitochondrial ADP / ATP carrier and cell membrane 52 000 peptide were positive in
      18 patients with DCM, while negative in controls. The antibodies induced
      cytotoxic damage with time-dependent and enhanced Ca-current in cardiac myocytes.
      The increasing amplitude of peak Ca(2+)-current was 100 pA-840 pA (n = 8) in
      different dilution of the antibodies. The effect of the antibodies might be
      inhibited by verapamil, and were null in controls (n = 4). CONCLUSIONS: The above
      findings suggest that an increase in the antibody-mediated Ca(2+)-current of
      cardiac myocytes is related to the cytotoxic damage in dilated cardiomyopathy.

PMID- 8758308
TI  - Transplantation of encapsulated neonatal porcine islet-like cluster cells into
      diabetic rats.
AB  - OBJECTIVE: To evaluate the function of alginate poly-L-ysine membrane in
      protecting porcine to rat islet xenografts. MATERIAL AND METHODS: Newborn porcine
      islet-like cluster cells (ICC) were obtained by digesting pancreas with type XI
      collagenase. After 2-3 days' incubation, encapsulated ICC were formed through
      instrument. In vitro, insulin release and insulin stimulating test was performed.
      In vivo, encapsulated ICC were transplanted into streptozotocin-induced diabetic
      rats. RESULTS: Unlike ICC only (insulin can be tested within 14 days)
      encapsulated ICC maintained insulin release at certain level for nearly 28 days.
      High insulin response to 16.7 mM glucose and 10 mM theophylline significantly
      differed from low insulin response to 5.6 mM or 16.7 mM glucose (P < 0.01).
      Extended survival of porcine ICC xenografts implanted in diabetic rats had been
      achieved by encapsulation. After transplantation, rats sustained normal glycemia
      for average 4 months. The capsules with ICC obtained from experimental group
      could be stained with neutral red. Insulin release of survival capsules with ICC
      in response to 16.7 mM glucose and 10 mM theophylline was 3 times more as
      compared to the insulin response to 5.6 mM glucose. Sections of encapsulated ICC
      (H&E) showed fairly good cell clusters and the membranes were generally free of
      fibrosis and host cell adherence. CONCLUSION: Artificial membrane can protect
      discordant islet xenografts from rejection.

PMID- 8758309
TI  - Urinary D-glucaric acid excretion in idiopathic neonatal jaundice.
AB  - OBJECTIVE: To determine the extent to which immaturity of hepatic microsomal
      enzyme activity might contribute to physiological jaundice. METHODS: Urinary
      excretion of D-glucaric acid, expressed in mumol glucaric acid/ mmol creatinine,
      was measured in 122 Chinese full-term healthy newborn babies during the first
      five days of life. Among the 122 babies, 22 were born by normal spontaneous
      delivery at the British Military Hospital and 100 were born by caesarean section
      at the Prince of Wales Hospital. RESULTS: In all babies the excretion of D
      glucaric acid was highest on the first day of life and gradually decreased over
      the following 5 days. Five babies born by spontaneous delivery and six babies
      born by caesarean section developed jaundice during the study period. The
      excretion of D-glucaric acid in the jaundiced babies was significantly higher on
      the first two days than in the non-jaundiced babies. CONCLUSIONS: D-glucaric acid
      excretion was increased in jaundiced newborn babies in the first few days of
      life. This finding does not indicate less liver microsomal enzyme activity in the
      jaundiced babies compared to those non-jaundiced. On the contrary, it suggests
      that in idiopathic neonatal jaundice compensatory mechanism might operate from a
      very early stage to excrete a higher bilirubin load that might be present through
      haemolysis.

PMID- 8758310
TI  - Very low density lipoprotein and oxidized very low density lipoprotein induce
      monocyte chemotactic protein 1 in rabbit aortic smooth muscle cells.
AB  - OBJECTIVE: To understand whether very low density lipoprotein (VLDL) and
      oxidatively modified very low density lipoprotein (OX-VLDL) can stimulate
      vascular smooth muscle cells (SMCs) to express high level of monocyte chemotactic
      protein (MCP-1) mRNA. METHODS: LDL and VLDL were isolated from normal blood
      donors by density gradient ultracentrifugation and oxidatively modified by adding
      CuCl2 and incubation at 37 degrees C for 24 hours. Rabbit aortic SMCs were
      cultured by a substrate-attached explant method, and their total RNA was
      extracted by guanidinium isothiocyanate method. The expression of MCP-1 mRNA in
      SMCs was examined by dot blotting analysis using a probe of gamma-22P-end-labeled
      35-mer oligonucleotide. RESULTS: Dot blotting analysis showed that cultured SMCs
      can express MCP-1 mRNA and the level of MCP-1 mRNA was increased significantly in
      SMCs after 24-hour coculture with VLDL (6-fold) and OX-VLDL (20-fold).
      CONCLUSIONS: VLDL and OX-VLDL both can induce MCP-1 mRNA expression in cultured
      rabbit aortic SMCs and the latter is more effective than the former.

PMID- 8758311
TI  - Effects of low dose gamma-ray irradiation on peripheral leukocyte counts and
      spleen of mice.
AB  - OBJECTIVE: To study the effects of low dose gamma-ray irradiation on peripheral
      leukocyte counts and spleen weight of mice. MATERIALS AND METHODS: Two hundred
      male mice of ICR strain were divided into four groups. Group A served as normal
      control. Groups B, C and D, the experimental groups were treated with 5, 50 and
      100 cGy (exposure dose in air) of whole body gamma-ray irradiation respectively.
      The leukocyte counts and its differential counts, body weight and the spleen
      weight of mice were measured on days 1, 5, 12, 19, 26 and 33 after irradiation.
      The relative spleen weight derived from the data of body weight and spleen weight
      was also calculated in tested animals. RESULTS: The leukocytes and its
      differential counts and relative spleen weight in mice decreased after 100 cGy
      gamma-ray irradiation. Fifty cGy gamma-ray irradiation could inhibit the
      leukocyte and its differential counts. The lowest dose, 5 cGy had no considerable
      damage. CONCLUSIONS: One hundred cGy of 137Cs gamma-ray irradiation had an
      inhibitory effect on counts of total leukocyte, lymphocyte, neutrophil, monocyte,
      spleen weight and body weight, while 50 cGy gamma-ray irradiation had an evident
      inhibition on peripheral leukocytes and its differential counts in mice. However,
      5 cGy gamma-ray irradiation had no obvious inhibition in the tested mice in the
      period of the investigation.

PMID- 8758312
TI  - Effect of interferon-gamma on antigen-induced eosinophil infiltration into the
      mouse airway.
AB  - OBJECTIVE: To investigate whether murine recombinant interferon-gamma (IFN-gamma)
      is capable of inhibiting antigen-induced eosinophil (EOS) infiltration into the
      mouse airway. MATERIALS AND METHODS: BALB/c mice were sensitized and challenged
      repeatedly with ovalbumin (OVA) to develop an allergic airway inflammation model.
      The experimental mice were given injection of different doses of IFN-gamma. The
      numbers of EOS in bronchoalveolar lavage fluid (BALF) from each group were
      counted, and concentrations of interleukin (IL)-5 in supernatants of cultured
      spleen cells were detected. RESULTS: In sensitized mice challenged with OVA 20
      minutes once a day for 6 days, the number of BLAF EOS was 9.53 +/- 0.84 x
      10(5)/ml. However, no EOS could be found in BALF from mice without OVA
      sensitization and challenge. In mice treated with IFN-gamma, doses of IFN-gamma
      (1.0 x 10(3), 1.0 x 10(4), 1.0 x 10(5)U/KG) produced 29.8% (P < 0.05), 55.7% (P <
      0.01), and 69.0% (P < 0.01) inhibition of eosinophilia, respectively. The results
      also showed that IFN-gamma prevented antigen-induced EOS recruitment into airway
      accompanied be decrement of levels of IL-5 with a dose-related response.
      CONCLUSION: IFN-gamma is capable of inhibiting EOS infiltration into mouse airway
      by inhibiting the production of IL-5. Our results suggested that IFN-gamma may be
      of value in treating asthma in human beings.

PMID- 8758313
TI  - Stereotactic intratumour irradiation with nuclide for craniopharyngiomas.
AB  - OBJECTIVE: Craniopharyngiomas is a kind of intractable tumor in neurosurgery.
      Since the radical excision is very difficult and occasionally hazardous because
      of its deep location and close neighbouring to critical cerebral structures, it
      is necessary to look for a simple and effective method. PATIENTS AND METHODS:
      Stereotactic intratumour irradiation with instillation of nuclide colloid was
      performed in 220 patients with craniopharyngiomas (altogether 265 times), of
      whom, 130 were male and 90 female. Their ages ranged from 5 to 69 years. The
      syndromes of optic path's impairment were present in all of the patients. CT or
      MRI scan showed cystic tumour in 125 patients, solid and cystic in 80 and solid
      in 15. No severe complications and death were related to the operation. RESULTS:
      150 patients were followed up for 2 months to 7 years (average 3.5 years).
      Tumours disappeared in 92 patients (61.4%), decreased dramatically in 20 (13.4%),
      decreased less than 50% in 19 (12.6%), and increased in 15 (10%); and there were
      4 deaths (2.6%). CONCLUSIONS: Stereotactic intratumour irradiation with
      instillation of nuclide colloid is effective in the patients with
      craniopharyngiomas. Beta-emitting isotopes (P-32 and Y-90) are the preferred
      internal radiation source because of their limited penetration of the energy
      released and the greater ease of handling. A calculated dose of 20 000 rads to
      the cyst wall is recommended.

PMID- 8758314
TI  - Experience in prevention of serious complications of laparoscopic
      cholecystectomy.
AB  - OBJECTIVE: To study the causes and prevention of the complications of
      laparoscopic cholecystectomy (LC). PATIENTS AND METHODS: Based on experience with
      2 428 cases, the following should be paid attention to when dissecting and
      separating adhesions around the gallbladder and of the Calot's triangle. The best
      method for the prevention of mistaking the common bile duct (CBD) for the cystic
      duct is to find the junction of the cystic infundibulum and duct, separate the
      gallbladder wall along the infundibulum, and transect the cystic duct at the
      junction with the infundibulum. If dense adhesions around the gallbladder or of
      the Calot's triangle are met with, LC should be abandoned and open the
      cholecystectomy (OC) should be used instead. In separating the Calot's triangle,
      blunt dissection should be used to avoid burning the extrahepatic bile duct
      (EHBD), and blind hemostasis should be avoided. If the cystic artery lies in the
      upper part and the back of the cystic duct, the cystic duct should be dissected
      out, clipped and cut first, then the cystic artery be dealt with. If the cystic
      artery is in the front part of the pedicle of the gallbladder, the artery should
      be separated, clipped and cut first. Injury to the adjacent organs may be avoided
      by using electric coagulating hook correctly and avoiding accidental damage to
      the viscera, and keeping from viscera injury due to current chemotaxis in the
      closed cavity of the body. RESULTS: A total of 2427 patients were cured. One
      patient died of frequent episodes of supraventricular tachycardia and pneumonia
      on the 21st day after LC. CONCLUSION: If LC surgeons follow the above said
      principles of LC technique. LC is very safe for patients with benign diseases of
      the gallbladder.

PMID- 8758315
TI  - Endovascular embolization with self-made silk segment suspension in a rabbit
      model.
AB  - OBJECTIVE: To evaluate the efficacy and the histologic changes caused by self
      made silk segment suspension as an agent for endovascular embolization of the
      external carotid artery of rabbit. METHODS: Three different silk suspension were
      used to perform selective endovascular embolization of the external carotid
      artery in 21 rabbits. Postembolization changes were investigated by angiography,
      light and electron microscopy, and behavioral and functional examination made in
      various groups of rabbits. RESULTS: The vascular changes in the group of simple
      silk segment were limited. The intima became thinner, while the media and
      adventitia were intact. However, in groups of ethanol-or estrogen-soaked silk
      segments, there was evident destruction of all layers of the vascular wall,
      including the intima, the media and the adventitia. CONCLUSIONS: Estrogen- or
      ethanol-soaked silk suspension is ideal and reliable for endovascular
      embolization, with the former being more effective than the latter. The
      obliteration caused by the suspension of simple silk segment was due to
      mechanical packing and compression plus incomplete thrombosis, which is likely to
      result in recurrence through compensatory collateral circulation.

PMID- 8758316
TI  - Effects of enflurane and isoflurane anesthesia on the pharmacokinetics of
      pancuronium in adult patients.
AB  - OBJECTIVE: To evaluate the effects of 1 MAC of enflurane or isoflurane anesthesia
      on the pharmacokinetics of pancuronium. METHODS: Eighteen adult patients
      undergoing the elective plastic surgery were randomly divided equally into 3
      groups, namely, Group 1 (control group), Group 2 (enflurane group) and Group 3
      (isoflurane group). Anesthesia was maintained with thiopental and 67% N2O-O2 in
      Group 1, 1 MAC enflurane in Group 2 and 1 MAC isoflurane in Group 3. After
      administration of a bolus of pancuronium 100 micrograms/kg, an improved
      fluorimetric assay was used to determine the serum concentrations of pancuronium
      and the pharmacokinetic variables of pancuronium were calculated with a 3P87
      program. RESULTS: The disposition of pancuronium may be well described
      mathematically by a two-compartment open model. The results showed that in
      comparison with the control group, patients in Group 2 and Group 3 had a longer
      T1/2 beta and MRT. The patients in Group 2 had the slower K10 and lower CL than
      those in the control group. There were no significant differences among the three
      groups in T1/2 alpha, V1, V2, Vdss, V beta, K21, K12 and AUC. CONCLUSION: During
      enflurane and isoflurane anesthesia, CL of pancuronium decreased, and T1/2 beta
      and MRT of pancuronium were prolonged in our patients, so duration of the
      effective plasma concentrations of pancuronium was much longer. As a result, the
      effects of enflurane and isoflurane of the pharmacokinetics of pancuronium may be
      part of reason why two drugs extended the duration of neuromuscular depression
      produced by pancuronium.

PMID- 8758317
TI  - A prospective randomized placebo-controlled trial of low-dose aspirin for
      prevention of intra-uterine growth retardation.
AB  - OBJECTIVE: To evaluate the effects of low-dose aspirin on placental circulation
      and on the prevention of intrauterine growth retardation (IUGR). MATERIAL AND
      METHODS: We conducted a prospective randomized, double blind, controlled clinical
      trial in 84 pregnant women (mainly nulliparous women) at high risk of IUGR. From
      the 28th-30th week of gestation onward, low dose aspirin (75 mg daily, study
      group, n = 40) or placebo (control group, n = 44) was given consecutively for 6
      to 8 weeks. Pulse-wave umbilical artery Doppler velocimetry was measured before
      and after drug use. RESULTS: The mean value of systolic/diastolic ratio of
      umbilical artery flow velocity waveforms in the study group was significantly
      lower than that in the control group after drug use, but there was no difference
      between the two groups before drug use. The incidences of IRGR and preeclampsia
      in the study group (7.5% and 10.0% respectively) were significantly lower than
      those in the control group (27.3% of both). No adverse effects of low dose
      aspirin on both mother and fetus were observed. CONCLUSIONS: Low dose aspirin
      administration (75 mg daily) beginning at the early stage of third trimester may
      improve the fetoplacental circulation, and thus prevent IUGR and/or preeclampsia
      effectively.

PMID- 8758318
TI  - Cataract extraction and intraocular lens implantation with anterior vitrectomy in
      children.
AB  - OBJECTIVE: Extracapsular cataract extraction (ECCE) with selective intraocular
      lens (IOL) implantation has been the choice of the treatment for children with
      cataracts. With regard to surgical technique, ECCE with anterior segment
      vitrectomy has shown some success in reducing complications. Formation of a
      secondary membrane and opacity of the posterior capsule, however, are still major
      postoperative complications. To reduce these complications, we modified current
      surgical procedures with minimal incisions and manipulations. PATIENTS AND
      METHODS: ECCE with anterior segment vitrectomy was performed using Storz
      Protage's system in 84 eyes of 58 children ranging in age from 14 months to 14
      years. Of 70 eyes of children aged above 3 years, IOLs were implanted
      simultaneously. Vision improvement and incidence of postoperative complications
      were compared with other standard procedures to determine the benefits of the
      operation for children with cataracts. After the anterior capsule was opened by
      continuous circular capsulorhexis or envelope-form capsulectomy, the lens cortex
      was excised. Subsequently, the IOL was implanted into the bag. RESULTS: Nine-30
      months follow-up showed that all of the central area of the posterior capsule
      remained clear except one eye in which a secondary membrane was partially formed
      on the anterior surface of vitreous. No other operative or postoperative
      complications occurred. CONCLUSIONS: The results indicate that the modified
      procedure is beneficial in the prevention of secondary cataract formation and
      other postoperative complications in a short term follow-up, however, a long-term
      follow-up is warranted to evaluate its role in pediatric cataract surgery.

PMID- 8758319
TI  - Correlation of 137Cs-induced micronuclei with survival fraction in human HT29
      cancer cells.

PMID- 8758320
TI  - Renovascular hypertension caused by traumatic arteriovenous fistula.

PMID- 8758321
TI  - Congenital absence of pericardium: report of 3 cases.

PMID- 8758322
TI  - A case of toxoplasmatic rhinitis and laryngitis.

PMID- 8758323
TI  - Community control of hypertension.

PMID- 8758324
TI  - Management of acute myocardial infarction.

PMID- 8758325
TI  - Gene therapy of familial hypercholesterolemia.

PMID- 8758326
TI  - Thrombolytic intervention of acute myocardial infarction in the 1990s.

PMID- 8758327
TI  - Applications of bio-techniques on treatment of cardiovascular diseases.

PMID- 8758328
TI  - Advances in the study on rheological behavior of leukocyte during severe shock.

PMID- 8758329
TI  - Construction and application of human chromosomal specific DNA probe pools.

PMID- 8758330
TI  - Clinical epidemiology in China.

PMID- 8758331
TI  - Tuberculosis in patients with chronic renal failure in China.

PMID- 8758332
TI  - Present status of radiation oncology in China. Second survey of Chinese Society
      of Radiation Oncology.

PMID- 8758333
TI  - Hot spots of hepatitis B virus for genetic mutation in Chinese patients and its
      clinical significance.

PMID- 8758334
TI  - Radiation risks: threshold or no threshold. The centenary of the discovery of X
      rays by W.C. Roentgen.

PMID- 8758335
TI  - Recent advances in the study of molecular biology of bladder cancer in China.

PMID- 8758336
TI  - Progress in surgical techniques in renal graft plantation. Anastomosis with
      titanium staplers.

PMID- 8758337
TI  - Experimental and clinical study on hepatobiliary surgery in China.

PMID- 8758338
TI  - A flow cytometric study on giant cell tumor of bone.
AB  - OBJECTIVE: Giant cell tumor of bone (GCT) is a comparatively common bone tumor in
      Chinese. Though GCT is generally considered as a benign tumor, it can pursue an
      aggressive course. The present study attempts to clarify whether the flow
      cytometric study can be an useful tool for prognosis of GCT patients. METHODS:
      DNA content and cell cycle studies on 96 pathologically confirmed GCT specimens
      and anti-GCT monoclonal antibody (GCF-5 McAb) labeling study on 30 GCTs were made
      by flow cytometry. RESULTS: 29 GCTs (30.2%) exhibited aneuploid and 67 (69.8%)
      diploid. Of 71 primary tumors, 16 (22.5%) exhibited aneuploid. The DNA index was
      0.97+0.15, and the average S, G2/M phase cells 15.23+6.15%. Of 25 recurrent
      tumors, 13 (52%) were aneuploid, with an average DI of 1.08+0.17. The average S,
      G2/M phase cells was 19.56+7.12%. Between the primary and recurrent tumor groups,
      there was significant statistical difference both in S, G2/M phase cell
      percentage (P < 0.05) and DNA content (P < 0.01). There was no significant
      difference between Jaffe's grade I and grade II groups in DNA content or in S,
      G2/M phase cell percentage. GCF-5 McAb could combine with almost all cells of S,
      G2/M phase and part of the cells in G0/G1 phase. Significant relationship existed
      (r=0.468, P < 0.05) between the percentages of S, G2/M phase cells and GCF-5
      positive cells. Between the primary and the recurrent tumor groups, there was a
      significant difference in the percentage of both S, G2/M phase cells and GCF-5
      positive cells. CONCLUSION: Apparently flow cytometric study is of value in the
      evaluation of the biological behavior of GCT as well as the prognosis of the
      patients.

PMID- 8758339
TI  - Effects of glycyrrhizae and glycyrrhizic acid on cellular immunocompetence of
      gamma-ray-irradiated mice.
AB  - OBJECTIVE: To investigate the effects of glycyrrhizae (GL) and glycyrrhizic acid
      (GA) on cellular immunocompetence in the gamma-ray-irradiated mice. MATERIALS AND
      METHODS: Tested mice of ICR strain were treated with GL and GA for 10 days
      continuously after 4 Gy gamma-irradiation. The counts of total leukocytes,
      lymphocytes, neutrophils and monocytes in peripheral blood of mice were measured.
      The blastogenic responses of splenocytes to mitogens, such as PHA, PWM, Con A and
      LPS were also detected. The cellular immunocompetence was measured by 3H
      thymidine incorporation in each tested mouse. RESULTS: The leukocytes and their
      differential counts decreased in gamma-irradiated mice. The blastogenic responses
      of splenocytes to mitogens were inhibited by gamma-ray irradiation. GL and GA
      were effective in enhancing the recovery of leukocyte count and the blastogenic
      responses of splenocytes to mitogens, such as PHA, PWM, Con A and LPS from the
      inhibition of 4 Gy gamma-irradiation. CONCLUSIONS: Four Gy gamma-ray irradiation
      can decrease leukocytes and their differential counts, and the blastogenic
      responses of splenocytes of mice. GL and GA can help the recovery of the cellular
      immunocompetence in the gamma-irradiated mice.

PMID- 8758340
TI  - Effects of gypenosides on cellular immunity of gamma-ray-irradiated mice.
AB  - OBJECTIVE: To investigate the effects of gypenosides (Gs) on cellular
      immunocompetence in the gamma-ray-irradiated mice. MATERIALS AND METHODS: Tested
      mice of ICR strain were treated continuously with Gs for 10 days before or after
      4 Gy gamma-irradiation. Body weight and splenic weight of mice were measured. The
      blastogenic response of splenocytes to mitogens, such as PHA, Con A and LPS were
      also detected. The cellular immunocompetence was measured by 3H-thymidine
      incorporation in each tested mouse. RESULTS: Body weight as well as splenic
      weight decreased in gamma-ray-irradiated mice. The blastogenic responses of
      splenocytes to mitogens were inhibited after gamma-ray irradiation. To treat with
      Gs was effective to enhance the recovery of body weight, splenic weight and
      immunocompetence in gamma-ray-irradiated mice from radiation damage. CONCLUSIONS:
      Four Gy gamma-ray irradiation could decrease splenic weight and cellular
      immunocompetence of mice. Gs could help the recovery of the splenic weight and
      cellular immunocompetence in gamma-ray-irradiated mice.

PMID- 8758341
TI  - Evaluation of the redox tolerance index on hepatic energy reserve of hepatitis B
      patients.
AB  - OBJECTIVE: To detect the redox tolerance index (RTI) for hepatic energy reserve.
      PATIENTS AND METHODS: 27 patients with chronic active hepatitis B (CAH) and 34
      patients with post-hepatitis B liver cirrhosis (LC) were studied. RESULTS: The
      RTI was significantly lower in CAH and LC cases than in normal controls (P <
      0.01). There was no difference between CAH and LC. The RTI of decompensated LC
      was significantly lower than that of the compensated LC (P < 0.05), indicating
      that there was no correlation between RTI and the parameters of routine liver
      functions. CONCLUSION: It is suggested that the RTI based on redox theory is
      effective and accurate in predicting hepatic energy reserve.

PMID- 8758342
TI  - Selective arterial embolization in the management of internal bleeding caused by
      trophoblastic diseases.
AB  - OBJECTIVE: To evaluate the efficacy and safety of selective arterial embolization
      in the management of internal bleeding caused by trophoblastic diseases. PATIENTS
      AND METHODS: Four patients with internal bleeding caused by trophoblastic
      diseases were diagnosed with arteriography and treated with selective arterial
      embolization as a life-saving measure. Effect of controlling bleeding was
      assessed by follow-up arteriogram and clinical observation. RESULTS: The
      embolization successfully controlled the bleeding in all patients. Operation time
      was short with a mean of 42 minutes. The shock was corrected dramatically. Fever
      and pain were common complications. CONCLUSION: Selective arterial embolization
      is a life-saving measure in the management of internal bleeding caused by
      trophoblastic diseases.

PMID- 8758343
TI  - In vivo effect of high energy shock waves on growth and metastasis of the
      heterografted tumors of nude mice.
AB  - OBJECTIVES: To examine whether high energy shock waves (HESW) can inhibit tumor
      growth in vivo and whether it can promote the metastasis of the heterografted
      tumors of nude mice. MATERIALS AND METHODS: Observations were made on the effect
      of HESW on tumor growth, histological and ultrastructural (transmission electron
      microscope, TEM) variations and metastasis to lymph nodes and viscera in the nude
      mice with heterografted tumors. The Dornier HM3 lithotripter was used under the
      working voltage of 15 kV, the impulse number being 0, 400 and 800 respectively,
      the temperature of waterbath, 35-37 degrees C and the impulse rate, 60/min.
      RESULTS: HESW did have cytotoxic effect on tumors in vivo, including acute and
      chronic lethal effects and growth inhibitory effect, and it could act on levels
      of cell membrane, cytoplasmic organelles and nuclear chromatin. At a definite
      working voltage, this effect was positively proportional to the impulse number.
      The action mechanism of HESW in vivo might be direct mechanical damage and
      indirect inhibition of tumor growth as a result of causing damage to the blood
      supply. Histological examination showed no metastatic foci to the lymph nodes and
      viscera of the nude mice with the heterografted tumors. CONCLUSIONS: HESW do
      inhibit tumor growth in vivo, but temporarily. This observation showed no tumor
      metastasis in the nude mice after the impulsion of HESW, but further studies on
      this topic are needed. It can be predicted that HESW will become a clinical
      method to treat the tumors after further investigation on its mechanism of
      action.

PMID- 8758344
TI  - Relationship between chondroitin sulfate proteoglycan and coronary
      atherosclerosis in the youth.
AB  - OBJECTIVE: To study the relationship between chondroitin sulfate proteoglycan
      (CSPG) and coronary atherosclerosis in youth. MATERIAL AND METHODS:
      Immunohistochemistry of chondroitin sulfate proteoglycan and SM-alpha-actin was
      performed on 39 human coronary arteries, including normal vessels and vessels
      with fatty streaks, intermediate lesions and plaques. Some of the lesional
      vessels were taken for beta-lipoprotein immunohistochemical study. CSPG contents
      were quantitated by image analyzer and the coronary arteries from one heart were
      processed for immunoelectron microscopy. RESULTS: The range of CSPG distribution
      was extensive and CSPG area density was increased significantly in the intima
      with atherosclerotic lesions. The increase of CSPG was parallel to the numbers of
      smooth muscle cell (SMC) with positive SM-alpha-actin reaction and was likely
      related to the phenotype transformation of SMC. Similar distribution of beta
      lipoprotein and CSPG were found within the lesional regions. CONCLUSIONS: The
      increase of CSPG in atherosclerotic lesion may be an important factor resulting
      in the deposition of lipids in the vascular wall so as to promote the formation
      and development of atherosclerosis.

PMID- 8758346
TI  - A new method of early diagnosis of fat embolism syndrome. An experimental study
      of the pulmonary microvascular cytology.

PMID- 8758345
TI  - Diagnosis and treatment of acute focal bacterial nephritis.
AB  - OBJECTIVE: Acute focal bacterial nephritis (AFBN) or acute lobar nephronia
      represents an acute localized non-liquefactive infection of the kidney caused by
      bacterial infection. The main manifestations consist of fever, chills, abdominal
      pain, flank pain, and tenderness and percussion pain of the costoverbral angles.
      Ultrasound and CT examinations identify the renal parenchymal space-occupying
      lesion which may resemble renal abscess or carcinoma. The clinical symptoms and
      the renal mass disappear following anti-infection treatment. METHODS AND RESULTS:
      Between January 1985 and May 1994, we treated 15 patients with AFBN, 10 men and
      five women, aged 16-56 years with an average of 30 years. The left kidneys in 11
      patients and the right kidneys in four were affected. All of the patients
      presented a fever and persistent flank pain on affected side. Ultrasound showed
      local enlarged renal volume and space-occupying masses with low level echoes. CT
      scans demonstrated focal enlargement of affected kidneys and low-density solid
      space-occupying lesions. CT reconstructions showed wedge-shaped masses. 14
      patients responded to appropriate parenteral antibiotics. The inflammatory masses
      diminished gradually in about 4 weeks. CONCLUSIONS: We believe that acute focal
      bacterial nephritis should be strongly suspected when a patient presents fever,
      chills and pain on the affected side and has a history of urinary tract
      infection. In addition, ultrasound and CT examinations suggest evidence of
      parenchymal space-occupying lesion, and the renal mass and its clinical symptoms
      disappear following anti-infection treatment.

PMID- 8758347
TI  - Uterine rupture in Zanzibar.

PMID- 8758348
TI  - Comments on some new viruses associated with old diseases in China.

PMID- 8758349
TI  - Human group B rotavirus: adult diarrhea rotavirus.

PMID- 8758350
TI  - Arbovirus survey in China in recent ten years.

PMID- 8758351
TI  - A new diarrhea pathogen: entero-adherent-invasive-toxigenic Escherichia coli.

PMID- 8758352
TI  - Bacterial L-forms research in China.

PMID- 8758353
TI  - Small hepatocellular carcinoma: past, present and future.

PMID- 8758354
TI  - The current situation of road traffic trauma.

PMID- 8758355
TI  - Clinical use of left ventricular assist device.

PMID- 8758356
TI  - Organ transplantation.

PMID- 8758357
TI  - Heart transplantation.

PMID- 8758358
TI  - IVF-ET program at Beijing Medical University.

PMID- 8758359
TI  - Rheum officinale: a new lead in preventing progression of chronic renal failure.

PMID- 8758360
TI  - Nephrological research.

PMID- 8758361
TI  - Hepatitis B virus variants and their significance in pathogenesis, prevention and
      treatment.

PMID- 8758362
TI  - Beta-amyloid protein and Alzheimer's disease.

PMID- 8758363
TI  - Direct neural regulation of the mammalian anterior pituitary.

PMID- 8758364
TI  - SJAMP-induced platelet aggregation defect.

PMID- 8758365
TI  - Membrane changes and metabolic disorders in erythrocytes of patients and rat
      models with aplastic anemia.

PMID- 8758366
TI  - Elevation of macrophage SeGSHPx gene expression prevents from its formation of
      foam cell and inhibits atherogenesis.

PMID- 8758367
TI  - Studies on traditional Chinese drugs.

PMID- 8758368
TI  - Development and research of Chinese herbal medicines.

PMID- 8758369
TI  - Immunologic effect of traditional Chinese drugs.

PMID- 8758370
TI  - Medical perspectives of nitric oxide.

PMID- 8758372
TI  - Recent advances in microsurgical anatomy.

PMID- 8758371
TI  - Raise the teaching and research level to fit development of diagnostic
      imageology.

PMID- 8758373
TI  - Age-related ocular diseases.

PMID- 8758374
TI  - Pathogenesis of idiopathic uveoencephalitis. The association of HLA-DR4 gene
      subtypes with Vogt-Koyanaki-Harada syndrome.

PMID- 8758375
TI  - The first one hundred AIDS cases in Hong Kong.
AB  - OBJECTIVE: To study the clinical and epidemiological characteristics of the first
      100 reported AIDS cases in Hong Kong. PATIENTS AND METHODS: The case records of
      the first 100 AIDS cases reported to the Department of Health were retrieved. An
      analysis was made on their demographic data, clinical and immunologic profile,
      treatment received as well as mortality. RESULTS: The AIDS patients were reported
      over a ten-year period, from February 1985 to March 1994. The majority of them
      were male, Chinese and between the age of 20 and 49. More than 80% acquired HIV
      via sexual contact. The most common primary AIDS- defining illness was
      Pneumocystis carinii pneumonia (PCP), which occurred in 46 patients. Eight
      episodes of Penicillium marneffei infection have been recorded. Fifty-nine
      patients have received antiretroviral therapy whereas PCP prophylaxis was given
      to 47 patients. The mean CD4 count at HIV and AIDS diagnosis was 394/microliters
      and 121 /microliters respectively. Sixty-seven patients were known to have died
      at the time of the analysis. PCP was the most common cause of death, accounting
      for over one-fifth of the cases. The median survival after AIDS diagnosis was
      less than 2 months for cases reported in 1985-1987 and over 15 months for those
      of 1990-1991. CONCLUSION: Pneumocystis carinii pneumonia was the most common
      initial AIDS-defining disease and cause of death in Hong Kong. Survival of the
      patients has gradually improved over the past few years.

PMID- 8758376
TI  - Histological and electron-microscopic observations on the mucosa of pediculate
      gastric wall graft transplanted to the intestines in Wistar rats.
AB  - OBJECTIVE: To study the machanism of the development of intestinal metaplasia
      through the transplantation of a flap of gastric wall with vascular pedicle to
      the intestines. METHODS: The pedicled gastric wall flaps of Wistar rats were
      transplanted to their duodenum, jejunum and colon respectively. After the
      operation the rats were killed at the 3th, 6th, 9th and 12th month respectively,
      and histological change of the gastric grafts was observed with optical and
      electron microscopy. RESULTS: Intestinal metaplasia was found in all the gastric
      grafts transplanted to the intestines and the alkaline phosphatase positive
      intestinal metaplasia was seen in the gastric graft mucosa transplanted to the
      duodenum and jejunum. CONCLUSIONS: The formation of intestinal metaplasia in the
      gastric mucosa may be related to a change of the microenvironment around the
      tissues, and gastric mucosa may differentiate into intestinal mucosa by the
      increase of pH value. The possible mechanism of the development of intestinal
      metaplasia was discussed.

PMID- 8758377
TI  - Photodynamic treatment of subcutaneous tumors in mice with photofrin II and Argon
      ion laser.
AB  - OBJECTIVE: To investigate the combined effects of photofrin (Pf) II and laser
      irradiation on mice bearing subcutaneous tumors. METHOD: Ehrlish ascites tumor
      cells (1 x 10(7)) were implanted subcutaneously into the breast area of ICR mice.
      The tumors, when grew up to 0.55 +/- 0.15cm3, was administered of laser
      irradiation (514.5nm, 112.5mW/cm2 for 11.12 min with a total energy 75j/cm2)
      after intraperitoneal injection of Pf II (5, 7.5, 10 and 15mg/kg body weight)
      once a day for three successive days. RESULTS: The mortality rate (MR120) in the
      tumor control was 93.7% and the mean survival time (MST120) was 46.6 days. The
      best therapeutic effect (50% mortality rate, 53.8% tumor control rate and mean
      survival time 86 days) was observed in the group treated with 7.5mg of Pf II per
      kg of body weight and total irradiation energy of 75J/cm2 (112.5mW/cm2 for 11.12
      min) with 514.5nm argon ion laser light. CONCLUSIONS: The effect on the survival
      rate of tumor cells and synthetic rates of DNA, RNA and protein were obviously
      inhibited, as the dose of pf II and laser irradiation increased.

PMID- 8758378
TI  - Prognostic significance of lymph node metastasis in surgical resection of
      esophageal cancer.
AB  - OBJECTIVE: Although surgery is relatively successful in eradicating local tumor,
      post-resection five-year survival rate for esophageal cancer is still lower than
      30%. Multiple factors are found to influence the long-term results after surgical
      treatment. However, recent investigations have focused on the significance of
      lymph node matastasis (LNM), which seems to be one of the most important factors
      leading to poor survival. Hence, the prognostic significance of LNM in surgical
      resection of esophageal cancer was studied. METHODS: The rate and degree of LNM
      were evaluated and their prognostic significance was investigated through a
      retrospective study of 474 patients with esophageal cancer treated by surgery
      alone. RESULTS: LNM was positive in 211 patients, with an incidence of 44.5%
      (211/474). A total of 5382 lymph nodes were resected and studied pathologically,
      among which metastasis was found in 690 nodes with an overall LNM degree of 12.8%
      (690/5382). The 5-year survival rate was 30.6% (145/474) in the entire series,
      12.8% (27/211) in patients with LNM, and 44.9% (118/263) in those without LNM.
      CONCLUSIONS: Surgery remains the first choice of treatment for carcinoma of the
      esophagus, and that meticulous lymph node dissection is an important practice of
      surgical oncology. However, in more advanced cases of this disease, surgery alone
      is of limited value in eradicating all cancer compromized tissue, and therefore
      the routine practice of extensive lymph node dissection in such cases may not be
      rewarding.

PMID- 8758379
TI  - Target imaging diagnosis of human brain glioma. Clinical analysis of 40 cases.
AB  - OBJECTIVE: To establish a method for localization and qualitative diagnosis of
      glioma. METHODS: The monoclonal antibody SZ-39 against human glioma was labelled
      with 131I and injected intravenously into 40 patients with intracranial occupying
      lesions proved by X-CT. 72 hours after 131I-McAb-SZ39 administration, cranial
      bone nuclide-imaging agent 99mTc-MDP was injected intravenously, and the patients
      were examined by SPECT scan with dual nuclide double channel tomography and
      special software. On radio-immuno-image, the immunocomplex formed by specific
      conjugation of 131I-McAb-SZ39 with target tissue was red, while the cranial bone
      incorporated with 99mTc-MDP was green. The location of the immunocomplex area
      could be identified by the superimposition of the images. RESULTS: 21 patients
      with positive targeting diagnosis of glioma showed the accuracy rate checked by
      SPECT was 81%(17/21) and by X-CT 48% (10/21). Seven patients with negative
      targeting diagnosis showed the accuracy rate checked by SPECT was 86%(6/7) and by
      X-CT 14% (1/7). Pathologically, the sensitivity of targeting SPECT to glioma was
      94.5%(17/18) and that of X-CT 55%(10/18). CONCLUSIONS: Targeting SPECT
      examination could be used for localization and qualitative diagnosis of glioma
      and make up the inadequacy of X-CT in the qualitative diagnosis of atypical
      incipient and recurrent glioma, meningioma, metastatic carcinoma, and
      inflammatory lesions of brain.

PMID- 8758380
TI  - A preliminary clinical report of automated lamellar keratoplasty with excimer
      laser keratectomy for correction of high myopia.
AB  - OBJECTIVE: To evaluate the therapeutic effects of automated lamellar keratoplasty
      combined with excimer laser keratectomy (ALK-E) for the correction of high
      myopia. METHODS: With the automated corneal shaper and Keracor 116 excimer laser,
      ALK-E was performed on 47 eyes of 40 cases with myopia of -8.00 to -30.00
      diopters (mean, -14.55D +/- 5.14D) and the highest astigmatism 7.00D.
      Postoperatively, all patients have been followed up for at least 3 months.
      RESULTS: The refractive status and visual acuity tend to be stable about 1 month
      postoperatively. For myopes below -15.00D, the mean refraction was -1.33D +/-
      1.05D at 3 months, and 66.7% achieved their preoperative best corrected visual
      acuity. For myopes over -15.00D, the mean refraction was -2.42D +/- 1.84D at 3
      months and 52.9% achieved their preoperative best corrected visual acuity.
      CONCLUSIONS: The early therapeutic results of ALK-E for treatment of high myopia
      are very promising. However, the operative techniques, parameters and remote
      therapeutic results remain to be further studied.

PMID- 8758381
TI  - [Limbal epithelial autograft transplantation for treatment of unilateral fibrous
      vascularized cornea caused by chemical burns].
AB  - OBJECTIVE: To provide healthy epithelial source for damaged cornea to prevent the
      invasion of conjunctival tissue for treatment of corneal vascularized opacity
      after chemical turns. METHODS: Limbal epithelial autograft transplantation was
      performed on 17 cases (17 eyes) with vascularized corneal opacity caused by
      chemical burns. RESULTS: Of 17 cases, the epithelial healing was stable in 15
      cases, and there was corneal graft transparency, improvement of visual acuity and
      without neovascularization in 13 cases. CONCLUSION: Limbal epithelial autograft
      Limbal epithelial autograft transplantation applied for reconstruction of
      palisades of Vogt to provide new stem cell source for injured limbus is a
      reasonable therapeutic method for treatment of vascularized corneal opacity
      caused by chemical burns.

PMID- 8758382
TI  - [Penetrating keratoplasty in children].
AB  - OBJECTIVE: The study was designed to approach the operative techniques of
      penetrating keratoplasty (PKP) in children and the influential factors on the
      rate of graft clarity. METHODS: PKP was performed on 33 eyes of 30 children whose
      corneal opacities resulted from various causes and they were followed for 6
      months to 3 years. RESULTS: The rate of graft clarity was 66.7% and 44.8% of
      these eyes were relieved from blindness. The poorest results achieved were in
      cases with congenital corneal opacity and the main cause of graft failure is
      endothelial immune rejection. CONCLUSION: Although the surgical results in
      children are poorer than that in adults, from the concern of prevention of
      amblyopia and cosmetic problem, it is necessary to perform the operation earlier.

PMID- 8758383
TI  - [Histopathological study on corneal incisions of radial keratotomy].
AB  - OBJECTIVE: The study was designed to improve the safety and predictability of
      radial keratotomy (RK). METHOD: Penetrating keratoplasty was performed on two
      eyes following RK for 2 months and 2 years respectively and their corneal buttons
      were studied histopathologically. RESULTS: The study revealed that at 2 months,
      there was only bridge-like healing of corneal epithelium, and oblique "V"-shaped,
      discontinuous or shallow incisions were seen, at 2 years, the healing process of
      partial incisions had not completed, and epithelial emboli were seen in the deep
      part of some incisions. CONCLUSION: Postoperatively, the incisions of RK are
      unstable for quite a long time. The RK incisions may influence other corneal
      surgeries performed on the same cornea in the future and are directly related to
      the healing and refractive outcome of RK. It is important to standardize the
      operative techniques.

PMID- 8758384
TI  - [A study of the immunopathology of Mooren's ulcer].
AB  - OBJECTIVE: The study was designed to investigate the immunopathology of bulbar
      conjunctive adjacent to Mooren's ulcer of the cornea and to evaluate the roles of
      immune regulation status, the adhesive action of conjunctival cells and
      leucocytes in the pathological tissue in the pathogenesis of the lesion. METHOD:
      15 limbal conjunctival specimens from 14 patients with the progressive Mooren's
      ulcer were examined by using immunohistochemical stainings for T-lymphocyte and
      its subsets (Pan-T, TH and TS), B-lymphocyte, intercellular adhesion molecule-1
      (ICAM-1) and lymphocyte function associated antigen-1 (LFA-1). RESULT: The ratio
      of T-helper to T-suppressor cells (TH/TS) in Mooren's ulcer group was
      significantly higher than that in the normal group, ICAM-1 was strongly expressed
      on conjunctival cells, whereas LFA-1 was strongly expressed in infiltrating
      leukocytes. CONCLUSION: The immune hyperfunction at the peripheral corneal lesion
      and its adjacent bulbar conjunctiva possibly is the direct cause of the
      pathogenesis of Mooren's ulcer. Simultaneously, the mutual action of ICAM-1 and
      LFA-1 might play an important role in the development of the disease.

PMID- 8758385
TI  - [Anti-herpes simplex virus action of combined therapy with cyclocytidine and
      ganciclovir].
AB  - OBJECTIVE: The study was designed to investigate the combined effect of
      cyclocytidine (CC) and ganciclovir (GCV) on herpes simplex virus-1 (HSV-1) in
      cell culture. METHODS: The 50% inhibition concentrations of HSV-1 plaque
      formation (IC50) of CC, GCV alone and in combination were determined by the
      inhibitory test of plaque formation. The combined anti-HSV-1 effect of CC and GCV
      was evaluated by a graphic method and fractional inhibitory concentration (FIC)
      indexes. RESULTS: IC50 of CC and GCV was 0.19 and 0.1 micrograms/ml,
      respectively. The combination of CC with GCV produced significantly synergistic
      activity against HSV-1 in cell culture. FIC indexes were all below 0.75. The
      combined therapy of CC and GCV can also decrease and delay the emergence of drug
      resistant variants. CONCLUSION: These results suggest that this combined therapy
      of CC and GCV may be a potentially effective means in the management of patients
      with HSV-1 ocular infection.

PMID- 8758386
TI  - [Early corneal topographic changes after intraocular lens implantation].
AB  - OBJECTIVE: The study was designed to investigate the early post-operative effect
      of the incision of extracapsular cataract extraction (ECCE) with intraocular lens
      (IOL) implantation on the whole corneal curvature. METHODS: TMS-1 Topographic
      System was used to record the changes in corneal refractive power and topography
      of 42 eyes within 3 months following the surgery through a 11 mm stepped limbal
      incision. RESULTS: The corneal topographic map showed that a vertical dumbbell
      configuration centered at the corneal top presented, the vertical corneal
      curvature at various radial distances steepened after the operation, the
      steepening at radial distance of 2.5 mm was much greater than that of 1.5 and 3.5
      mm and the steepening at the upper cornea was greater than that at the
      corresponding lower cornea. The postoperative vertical corneal steepening
      gradually flattened and the refractive power decreased. CONCLUSION: The
      topographic map early after ECCE with IOL implantation presents a flattening
      change of vertical corneal steepening corresponding to a with-the-rule
      astigmatism which decreases gradually.

PMID- 8758387
TI  - [The effect of mitomycin C on filtration surgery of glaucoma with poor
      prognosis].
AB  - OBJECTIVE: To determine the anticicatrization effect of mytomycin C (MMC).
      METHODS: We randomly divided 30 cases (40 eyes) into two groups: 21 eyes in MMC
      group and 19 eyes in control group. Intra-operatively, 0.4 mg/ml MMC was used in
      the trabeculectomy in MMC group, and no MMC was used in the control group. The
      post-operative follow-up periods ranged from 6 to 25 months (mean, 10.0 months).
      RESULTS: The successful rate of the operation of MMC group was 90.4% and that of
      the control group, 26.3% (P < 0.0001). The rate of eyes with functional filtering
      blebs was 17/21 and that of the control group, 4/19 (P = 0.002). Macular edema
      occurred in 3 eyes of MMC group and none in the eyes in the control group. There
      were no corneal complication and leakage of the wound. CONCLUSION: The results
      show that MMC can promote the formation of functional filtering bleb and elevate
      the successful rate of filtration surgery.

PMID- 8758388
TI  - [An ultrastructural study on human retina with late glaucoma].
AB  - OBJECTIVE: To study the pathologic changes of retina in glaucoma. METHOD: Retinas
      from 6 cases with absolute glaucoma were observed by transmission electron
      microscope. RESULT: It was found that the nerve fiber layer was significantly
      thin and the axons were severely damaged even lost; the ganglion cells nearly
      disappeared and a number of cell-like bodies were seen instead; the nerve cells
      of the outer and inner nuclear layers were degenerated, decreased in number, and
      disorderly arranged; the outer segments of the cone and rod cells became
      degenerative and edematous. CONCLUSION: In advanced glaucoma the degeneration and
      atrophy of the ganglion cells and their nerve axons were the major pathologic
      changes of the retina that lead to the permanent damage of visual function.

PMID- 8758389
TI  - [A clinical investigation on scleral reinforcement for treatment of high myopia].
AB  - OBJECTIVE: The study was designed to observe the therapeutic effects of scleral
      reinforcement in treatment of high myopia. METHOD: 86 patients (109 eyes) with
      high myopia were treated by scleral reinforcement using silicone sponge and
      heterogeneous sclera. RESULTS: Postoperatively, the naked visual acuity increased
      in 71.9% of all the eyes in 1-4 years of follow-up. 69.9% of them had a stable
      axial length, and the volume of blood flow in ophthalmic artery increased in some
      eyes. CONCLUSION: Scleral reinforcement has therapeutic effects in treatment of
      high myopia. The surgical techniques applied were mentioned.

PMID- 8758390
TI  - [An analysis on therapeutic effects of posterior scleral support operation for
      treatment of myopia].
AB  - OBJECTIVE: The therapeutic effects of modified posterior scleral support
      operation for treatment of myopia and its operative effect on ocular axial length
      in high myopia were analyzed. METHOD: Among 78 cases 151 myopic eyes having
      undergone this operation and followed for 6-12 months, there were 23 cases (43
      eyes) whose mean ocular axial length was compared with that of matched 20 cases
      (39 eyes) of myopia having undergone radial keratotomy alone and that of matched
      19 cases (38 eyes) without any operation. RESULT: The results showed significant
      differences. CONCLUSION: The modified operation is safe, of simple operative
      procedure and has definite effect on preventing the lengthening of ocular axial
      length in high myopia.

PMID- 8758391
TI  - [The purification and analysis of S-antigen in rabbit retina].
AB  - OBJECTIVE: S-antigen from rabbit retina was isolated and purified to investigate
      the immune mechanisms of experimental autoimmune uveoretinitis (EAU) and lay a
      foundation for its experimental treatment. METHOD: Two-step ion exchange
      chromatography was used for the purification of S-antigen and it was analyzed.
      RESULT: The analytical studies show that the molecular weight of the purified S
      antigen is 55,000, its isoelectric point is 6.40, and non-polar amino acid
      constitutes a relatively large proportion in its amino acids. Scanning tunnel
      electron microscope was used to investigate the configuration of S-antigen. It is
      elliptic globe-like. The purified S-antigen successfully induced the model of
      EAU. CONCLUSION: S-antigen purified by two-step ion exchange chromatography can
      be used for its own analytical studies and induction of EAU model.

PMID- 8758392
TI  - [Subconjunctival 5-fluorouracil polyphase liposome interference with scar
      formation in experimental filtration surgery].
AB  - OBJECTIVE: A comparative study was made to determine the effect of 5-fluorouracil
      (5-Fu) polyphase liposome and 5-Fu solution on the prevention of scar formation
      in filtration surgery. METHOD: 20 New Zealand white rabbits that underwent a
      standard trabeculectomy in both eyes were divided into two groups and each group
      consisted of 10 rabbits. Postoperatively, according to randomized fashion, in the
      first group, one eye received daily subconjunctival injection of 5 mg (0.2 ml) 5
      Fu solution and the fellow eye received equal subconjunctival amount of normal
      saline serving as the control, in the second group, one eye received once
      subconjunctival injection of 5 mg (0.2 ml) of 5-Fu ployphase liposome with every
      3 days apart and the fellow eye received the equal amount of subconjunctival
      injection of polyphase liposome serving as the control. RESULTS: Two weeks after
      the surgery, the eyes treated with 5-Fu solution in the first group and 5-Fu
      polyphase liposome in the second group showed marked reduction of intraocular
      pressure (IOP, P < 0.05) and the control eyes of both groups did not reveal any
      marked reduction of IOP as compared with preoperative IOP respectively.
      Morphometric analysis of the areas of fibrosis in histologic section demonstrated
      a significant decrease (P < 0.002) in episcleral fibrosis in the eyes treated
      with 5-Fu solution and 5-Fu polyphase liposome as compared with their control
      eyes respectively. Superficial punctate keratopathy occurred in two of the 5-Fu
      solution-treated eyes (20%) and no toxic reaction was noted in the 5-Fu polyphase
      liposome-treated eyes. CONCLUSION: Postoperatively, subconjunctival 5-Fu
      polyphase liposome instead of 5-Fu solution inhibits the scar formation at
      filtering site, and the therapy is safe and effective, leading to a higher
      success rate.

PMID- 8758393
TI  - [Protective effect of verapamil on light-induced rat retinopathy].
AB  - OBJECTIVE: In order to search for simple and effective medicine to protect light
      induced retinopathy. METHOD: We used verapamil as a protective agent. We measured
      the contents of the end product of lipid peroxidation, malondialdehyde (MDA), in
      the rat retinas immediately, 4 days, 15 days and 30 days after the damage in the
      damaged group and protective group, and observed their histopathologic structures
      and the integrity of the outer blood-retinal barrier. RESULTS: The results showed
      that the content of MDA in the normal retina was 0.36 +/- 0.07 nmol/mg, while in
      the damaged group the MDA levels at different times were 0.52 +/- 0.03 nmol/mg,
      0.70 +/- 0.20 nmol/mg, 0.52+/- 0.07 nmol/mg, and 0.47 +/- 0.03 nmol/mg
      respectively, being significantly different from that of the normal group. In the
      protective group, the MDA levels at different times were 0.40 +/- 0.04 nmol/mg,
      0.49 +/- 0.03 nmol/mg, 0.40 +/- 0.05 nmol/mg and 0.39 +/- 0.08 nmol/mg
      respectively, being significantly different from that in the damaged group at the
      corresponding times. In the damaged group, the histologic study showed that the
      retinal structures were damaged in various degrees at 4 days and most severely at
      15 days after light exposure and the outer blood-retinal barrier was also
      damaged, while in the protective group no significant pathologic changes of
      retina were seen. CONCLUSION: Verapamil is an effective protective medicine for
      light-induced retinopathy.

PMID- 8758394
TI  - [A study on cryotherapy of experimental posterior penetrating eye injury].
AB  - OBJECTIVE: The study was designed to investigate the effects of cryotherapy on
      intraocular tissues in ocular penetrating injury, and an experimental study was
      made on rabbits. METHODS: The penetrating injury models in both eyes of 23 (46
      eyes) pigmental rabbits were performed. Cryotherapy was applied after the
      operation in the left eye but not in the right eye (the control) of each animal.
      All the pupils of the eyes were dilated and examined by ophthalmoscope and B-scan
      at different time after the operation. Enucleations were performed at 2 weeks, 6
      weeks and 3 months and the enucleated eyeballs were examined pathologically by
      light and electron microscopy. The synchronous fundus and pathological changes
      were evaluated and analyzed statistically (Pearson Chi-square test). RESULTS: The
      intraocular reaction and proliferation in cryotreated group was much more severe
      than those in the control one (P = 0.027), especially in the vitreous (P =
      0.016). The incidence of tractional retinal detachment in cryotreated group was
      higher than that in the control. CONCLUSION: It is suggested that the
      prophylactic cryotherapy in the posterior penetrating ocular injury of rabbits
      increase intraocular proliferation.

PMID- 8758395
TI  - [An experimental study on effects of form deprivation on development of myopia].
AB  - OBJECTIVE: The study was designed to approach the pathogenesis of myopia. METHOD:
      Haisaik chickens were used to establish the animal models of myopia and form
      deprivation method was applied. Monocular eyelids were sutured for form
      deprivation on the 5th day after chicken birth. RESULTS: Form deprivation leads
      to myopic refractive abnormality (P < 0.001). The ocular anteroposterior axis (P
      < 0.005), transverse and vertical diameters lengthen (P < 0.05). In the mean
      time, obvious pathologic changes were found. The cartilaginous cell layer of the
      sclera became thicker, the numbers of chondrocytes and binucleate cells were
      greater, and the fibrous layer of the sclera was thinner. CONCLUSION: Form
      deprivation is the main cause of the development of myopia.

PMID- 8758396
TI  - [Control and elimination of measles].

PMID- 8758397
TI  - [Study on the subclinical infection of the recipients of measles vaccine].
AB  - Through observation to subclinical infection of the 71 children who had been
      inoculated against measles 12 years ago and then exposed to natural measles from
      three classes at a primary school, we have noticed: (1) Subclinical infection did
      exist among the crowd who were inoculation against measles; The rate of
      subclinical infection of the three classes was between 18.5%-75.0%, with an
      average of 45.1%. (2) The level of the HI Ab titer was between 1:2-1:16. The peak
      level was between 1:2 and/or 1:4. So the rate of subclinical infection who had
      been inoculation against measles but later exposed to natural measles would
      depend on the proportion of those whose titer of HI Ab was 1:2-1:4 in the crowd.
      (3) The epidemiological significance of subclinical measles infection lies in
      that it can actively keep and consolidate the level of immunity to certain extent
      in a crowd who had been inoculation against measles.

PMID- 8758398
TI  - [A prevalence study on HBV and HCV infection status in patients with hemopathy].
AB  - A prevalence study on Hepatitis B virus (HBV) and Hepatitis C virus (HCV)
      infection in 144 patients with hemopathy was carried out, using an enzyme linked
      immunosorbent assay (ELISA). The HBsAg, HBcAb and anti-HCV positive rates in sera
      of these patients were 9.72%, 36.81% and 24.31% respectively, comparing with data
      from healthy control subjects, 12.03%, 46.30% and 0.93% respectively. No
      correlation between HCV infection and patient's age or sex was noticed.
      Nevertheless the incidence of HCV infection was closely related to the history
      and the frequency of blood transfusion. The ALT level in sera of patients with
      HCV infection was higher than that of patients without HCV infection. The ALT
      level in sera was the highest in patients superinfected with HBV and HCV. Our
      results suggested that blood transfusion and receiving blood products were
      important routes of HCV transmission in patients with hemopathy.

PMID- 8758399
TI  - [An epidemiological study on influenza pandemic].
AB  - A cross-sectional epidemiological study on "the relationship between five
      variables [Fish, Pig, Duck, Chicken and Integrated Fish Farming (IFF)] and
      influenza pandemic" was carried out in 697 disease surveillance spots in the
      rural areas of Shandong & Henan provides. Results suggested that ducks might have
      played an important role in the ecology of influenza. Pigs did not seem to be a
      greater culprit in ecology of influenza but gave the inconsistent view with the
      hypothesis that IFF could lead to human influenza pandemic.

PMID- 8758400
TI  - [Screening on lameness caused by poliomyelitis in Anhui Province].
AB  - In 1992, a screening of poliomyelitis caused lameness among children under 15
      years of age was conducted to verify whether poliomyelitis has been absent in
      Anhui. A total number of 7,639 cases were diagnosed as poliomyelitis caused
      lameness. The prevalence rate was 0.44%, the rate was higher in plains than in
      hilly and mountainous areas. Rate was higher in ural than in urban areas. The
      disease mainly occurred in children at age below 3. The result showed that there
      were two epidemic peaks during 1976-1991, but the incidence rate tended to be
      declining. The incidence rate was the lowest in 1991. Many cases were not
      reported during 1976-1988.

PMID- 8758401
TI  - [Research on factors affecting neonatal tetanus and its prevention through
      immunization].
AB  - Neonatal Tetanus (NT) has been set by WHO as one of the most important diseases
      to be under control. Its incidence rate at some counties and cities in Southern
      Fujian province exceeded set out levels. Both retrospective and cohort studies
      were carried. It was found that in rural areas only 8.66% (319/3,683) pregnant
      women gave births at hospital and 94.85% (129/136) NT cases were delivered by
      untrained midwives. When TAT was tested in mothers and newborns, only 23.81% and
      20.65% of them reached protective level. This shows the main reasons for high NT
      incidence rate were due to poor medical treatment during delivery and low
      antibody level. Using tetanus toxin (TT) to fully immunize pregnant women, no
      side effects were observed and TAT antibody levels for mothers and newborns were
      increasing to reach 100% (99/99) and 93.94% (93/99) relatively. When immunizing
      women at child-bearing age with TT, 90.40% (113/125) of them still had TAT up to
      protective level in 3 years. A total number of 8,882 newborns whose mothers had
      been fully vaccinated with TT were investigated, no NT case occurred. Among 4,835
      newborns whose mothers did not receive vaccination, some NT cases were
      identified. The incidence rate was as high as 5.28%. These results showed that
      the TT vaccination in women at child-bearing age should be considered as the
      major strategy for NT prevention.

PMID- 8758402
TI  - [Study on the geographic distribution and serological typing of HFRS in Hebei
      Province].
AB  - Surveillance on the HFRS had been carried out during the period of 1986-1993.
      Rodent density ranged from 4.6%-12.2% with R.norvegicus exceeding 60% in all
      kinds of rodents. HV antigen carrier rate of R.norvegicus was 1.3%-7.5%, much
      higher than that among other rodents. A significantly positive correlation had
      been observed between the HFRS morbidity and the R.norvegicus density. Of 129
      specimens from HFRS patients, 89% belonged to the type of SEOV. In the eastern
      and centre Parts of Hebei plain, HTNV occupied 1.6%. A total number of 9,609 HFRS
      patients had been identified during the period of 1980-1993. The plain area in
      Hebei province was recognized as the major epidemic area. The key measure for
      decreasing the HFRS morbidity was deratizationin in the residential area in
      January and February and immunization with HFRS inactivated vaccine.

PMID- 8758403
TI  - [Serological survey on mycoplasma infection among three populations in Yunnan
      Province].
AB  - Mycoplasma infection in both female and male genital tract has attracted
      attention recently. 636 infertile and sterile cases together with 284 women with
      IUDs and 113 women with genital inflammatory complications after artificial
      abortion were detected through indirect hemagglutination test for serological
      survey on the frequency of ureaplasma urealyticum (Uu) and mycoplasma hominis
      (Mh) infection. Some of them were detected through isolated culture at the same
      time. Among the 636 infertile and sterile cases, the results showed that the
      antibody positive rate to mycoplasma was 26.10%. Among women with IUD, the
      antibody positive rate was 32.39%. However, the antibody positives rates among
      women with IUD shorter than three months were significantly higher than those
      prior to and three to twelve months after insertion of IUD (P < 0.01). Among the
      113 women after abortion, the positive rate was 46.02%. The positive rates of the
      three groups were significantly different from the control group (P < 0.001), and
      the antibody titers to mycoplasma were significantly higher than that of the
      control group. It is suggested that mycoplasma infection is one of the important
      causes for infertility and causing complication of genital inflammatory symptoms
      after abortion.

PMID- 8758404
TI  - [Preliminary study of microbiocide effect and its mechanism of electrolyzed
      oxidizing water].
AB  - Electrolyzed Oxidizing water (EO Water) is characterized by possessing higher
      oxidizing reduction potential (ORP), lower pH value and oxidizing potential.
      Under conditions of free organic matter, it was tested for microbiocide efficacy
      in laboratory. The results showed that EO water could completely kill all of the
      staphylococcus aureus and E. coli within 15 seconds, while for completely killing
      of spores of Bacillus subtilis Var. niger it would take 10 min. When it was used
      to destroy the antigenicity of HBsAg, 30 seconds was needed. The ORP and pH
      values of EO water were not obviously changed when stored in room-temperature
      with, airtight and light-free conditions for three weeks. Distilled water and
      physiological saline had little influence on the ORP and pH value of EO water,
      but organic matters and phosphates had greater influence upon the two values.

PMID- 8758405
TI  - [Study on the epidemiology of HP infection among 464 school staff in Henan
      Province].
AB  - An epidemiological study of Helicobacter pylori (HP) infection among 464 school
      staff was carried out by detecting sera urease antibody. The result showed that
      HP infection rate was 42.03% and increased with age. It was higher among persons
      with upper gastrointestinal symptoms and with gastric disease than without. The
      rate of HP infection tended to relate to factors as educational level, income,
      alcohol consumption but did not reach significant level statistically. HP
      infection did not seem to be related to gender, members in a family and smoking.

PMID- 8758406
TI  - [Analysis of population attributable risk of breast cancer in urban and mining
      districts inhabitants].
AB  - In order to study the risk factors associated with female breast cancer, two 1:2
      matched case-control studies were conducted from 1986 to 1993 in five cities in
      Hubei province and from 1991 to 1994 in Pingdingshan coal mining districts in
      Henan province. The results of multivariate conditional logistic regression
      analysis showed that history of breast diseases, number of births, age of first
      birth were major risk factors for breast cancer in urban inhabitants. Their
      adjusted attributable risks (PARs) were 0.3917, 0.3564, 0.1414 respectively. The
      combined population attributable risks (PAR) for the three factors was 0.7419.
      History of breast disease, number of births, menstrual disorder, family history
      of breast cancer were major risk factors in the Mining districts. Their PARs were
      0.1487, 0.4781, 0.1282, 0.0791 respectively. PAR for four factors was 0.6952.

PMID- 8758407
TI  - [Comparison between the plaque reduction neutralization test and the
      hemagglutination inhibition test in determination of human anti-measles
      antibodies].
AB  - In order to evaluate the difference between plaque reduction neutralization test
      (PNt) and hemagglutination inhibition (HI) test on human anti-measles antibodies,
      pre- and postimmunization sera collected from 328 infants aged 3-6 months who
      were immunized with Shanghai 191 measles vaccine, were detected by both methods.
      The results demonstrated that PNt was more sensitive than HI when they were used
      to measure the pre-immunization sera. No significant difference was found between
      these two methods when they were used to measure the post-immunization sera. PNt
      can be used to test low level maternal anti-measles antibodies in infants,
      especially for estimating the effect of maternal anti-measles antibodies on the
      immunogenicity of measles vaccine.

PMID- 8758408
TI  - [Measles virus and measles vaccine].

PMID- 8758409
TI  - [Current status of the prevention and treatment of measles].

PMID- 8758410
TI  - [Rates of hip fractures in Beijing China].
AB  - One-third of the world's hip fractures are said to occur in Asia, but there have
      been no validated studies of hip fracture rates in China. In 1988-1992 all 76
      hospitals in Beijing reported 820 hip fracture admissions coded as ICD-9.
      Checking against original discharge logs, medical records, X-ray reports,
      operation notes and operating room logs of a random sample of Beijing hospitals
      to discover underestimated and misclassified cases. In order to estimate hip
      fracture treated outside hospitals, we also interviewed a random sample of 2113
      women aged 50 and over with a 97% response rate in Beijing. Finally, we also
      surveyed 27 hospitals in the suburbs of Beijing, but have found that no Beijing
      residents had been treated for hip fracture outside the city. Based on the 1990
      China census, age-standardized rates (per 100,000) of hip fractures in Beijing
      were 88 for women, 97 for men. From 1988 to 1992, the rates in Beijing increased
      35% in women and 33% in men. This is the first validated population-based study
      on the rates of hip fractures in China that has confirmed the completeness and
      accuracy of reports of hip fracture cases and has estimated the degree of under
      reporting of hospital discharge. Hip fracture rates in Beijing are among the
      lowest in the world but may rise rapidly.

PMID- 8758411
TI  - [The trend of proportion among inpatients with gout in 21 hospitals during the
      past 15 years].
AB  - We analyzed data gathered from 21 hospitals in our country from 1979 to 1993 on
      the total number of hospitalized patients with the number of gout patients.
      Results showed that the proportion of hospitalized gout patients in 21 hospitals
      has increased sharply during the past 15 years (Chi2 = 823.4, P < 0.001). The
      constituent ratio of hospitalized gout patients in 13 hospitals in southern China
      increased abruptly (Chi2 = 650.9, P < 0.001); while the constituent ratio in 8
      hospitals in northern China increased to a lesser extent (Chi2 = 188.1, P <
      0.001). A significant difference was noticed between southern and northern China
      (Chi2 = 45.8, P < 0.001). During the past 15 years, the proportion of
      hospitalized gout patients has been increasing rapidly, with greater extent in
      the south. This is probably related to the economic development which improves
      the standard of living and to the changes of food structure.

PMID- 8758412
TI  - [Association of air pollution with unscheduled outpatient visits in Beijing
      Longfu Hospital, 1991].
AB  - Outpatient visits to Beijing Longfu Hospital, a community-based hospital, were
      analyzed to assess the association of air pollution with daily outpatient visits
      in 1991. Measurements of total suspended particulate (TSP) were available for 224
      days (mean was 359 micrograms/m3) and sulfur dioxide (SO2) for 221 days (mean was
      124 micrograms/m3). The effects of TSP and SO2 were assessed by linear
      regressions adjusting for temperature, humidity, seasons and the workdays as
      covariables with a Markov correction for auto-correlation in time series data.
      There was a significant exposure-response relationship between TSP level and non
      surgery outpatient visits but not for surgery visits. SO2 was only significantly
      associated with pediatric visits.

PMID- 8758413
TI  - [Vaginal colonization of group B Streptococcus: a study in 267 cases of factory
      women].
AB  - An epidemiologic study on vaginal colonization of group B streptococcus (GBS)
      from non-pregnancy women was carried out. Two hundred sixty seven female workers
      were studied. The carrier rate of GBS in vaginal specimens was 10.86%. Women aged
      45 years old and above had more cases with genital tract GBS colonization. Women
      with vaginal colonization had more history of miscarriage and using IUD. We did
      not find the positive correlations between vaginal colonization and oral
      contraceptive, ovarian cyst, hysteromyoma in our study group. Women with
      gynecologic inflammation had more cases with vaginal GBS colonization. There is a
      significant increase for women with vaginitis and cervicitis. Serotyping study
      showed that types III and II were the most frequent GBS types isolated from the
      carriers. Antibiotic sensitivity test showed that more than half GBS strains were
      resistant to oxcillin and amikacin.

PMID- 8758414
TI  - [A five years surveillance on neural system birth defects in rural areas of
      China].
AB  - A total number of 167,274 births were observed on birth defects in rural areas
      1968-1990 in China. The results showed that there were 361 cases of neural system
      defects, accounting for 31.45% in all birth defects. The incidence of neural
      system defects was 2.19% with hydrocephalus, anencephalus and spinal bifida
      0.89%, 0.87%, 0.36% respectively. The distribution of neural system birth defects
      showed that incidence in northern part of the country was higher than that of in
      the south while in winter--spring was higher than in summer--autumn. Results of
      unconditional logistic regression analysis demonstrated that risk factors were
      related to neural system defects as maternal education level, parity, delivery
      mode and lower birth weight.

PMID- 8758415
TI  - [An epidemiological analysis on the relationship between motorization and traffic
      mortality in China].
AB  - In order to explore the road accident which brings about a threat against
      residents' life. We applied motorized extent of city (MEC, the rate per 1,000
      persons possessing the number of vehicles), level of traffic safety (LTS, the
      mortality rate per 10,000 registered vehicles), level of personal safety (LPS,
      the mortality rate per 100,000 persons) to evaluate the relationship between
      secular trend of motorization and traffic mortality in China. Although increased
      by 100 times from 1949 to 1992, MEC was considered rather low in the whole
      country (MEC = 11.2%). When MEC was progressing while LPS was decreasing year
      after year, LTS has been improved since the late 1970s. The best records of MEC
      and LTS were noticed in Beijing and the best LPS was in Inner Mongolia.
      Throughout the 30 administrative areas, LPS has taken a favourable turn, while
      MEC and LTS abtained distinct improvement in certain areas. Thus one's personal
      safety is affected by both the synergism of motorization and the road safety
      level.

PMID- 8758416
TI  - [The relationship between integrated fish farming and human influenza pandemic].
AB  - The study was carried out for reviewing the hypothesis on the relationship
      between integrated fish farming (IFF) and human influenza A pandemic using study
      methods of longitudinal epidemiology, ecology and serology. Four rural villages
      with IFF, non-IFF and non-fish farming, selected from two provinces (Henan and
      Shandong of PRC) were investigated for the status about human influenza A
      epidemic and infections with human, duck, swine influenaz A viruses in those
      communities. The results put forward views on that there is no relation between
      IFF and the increase of incidence rate, infection rate and antibodies level to
      human influenza A virus. Duck may play an important role in the increase of
      infection rate to human influenza A viruses among human communities. Pigs seem
      not to play obvious role in the increase of infection rate to human influenza A
      viruses among human communities. Human, duck, swine influenza A viruses may
      spread among human duck and pigs communities interchangably.

PMID- 8758417
TI  - [A serological study on the infection of Helicobacter pylori among children].
AB  - Using ELISA method, anti-H. pylori IgG and IgM were detected in 181 sera from
      patients (aged 2-14 years) complaining of repeated midepigastical pain and 152
      sera of controls. The positive rate of anti-H, pylori IgG in the patients was
      53%, significantly higher than those of control groups (34.6%-35%), (P < 0.05).
      The presence of anti-H. pylori IgG in serum can assist in the diagnosis of H.
      pylori, but can not indicate the existence of H. pylori. There were no evident
      relationships between level of antibodies (anti-H. pylori IgG and IgM) and the
      degree of H. pylori infection, or the duration of disease. Children's H. pylori
      infection increases with age. Elder children have the same positive rate of anti
      H. pylori IgG as adults. Hence, eradication of H. pylori infection should be
      focused not only on adults but also on children.

PMID- 8758419
TI  - [A general discription and analysis of plague epidemiology in China during 1990
      1994].
AB  - The result of systematic and active surveillance indicates that the human cases
      increased dramatically in the 90's. The main reason was due to the renewed
      activity of R. flavipectus nidi in Yunnan Province, but has basically been under
      control. As the effort of prevention, enzootic plague in southeast costal and
      northeast regions has been stabilized for thirty to forty years. The policy of
      plague control in China is to put prevention first. The measures include
      surveillance, deratization and depulization, health education and emergency
      management in epidemic areas.

PMID- 8758418
TI  - [Nosocomial transmission of Helicobacter pylori through fiberoptic gastroscopy].
AB  - The relationship of nosocomial transmission of Helicobacter pylori (Hp) by
      fiberoptic gastroscopy was investigated. Hp was cultured from the materials
      obtained from the suction/biopsy channel (4/12 times) and biopsy forceps (3/10
      times). The positive rate of Hp was increased with times undertaking endoscopy in
      the past in elder patients with chronic gastritis. The rate from Hp negative
      transforming into positive also increased with the times of receiving endoscopic
      follow-up in the past in patients with Hp negative chronic gastritis. The average
      age of Hp positive patients were older in those patients under follow-up studies
      than that in randomly age-matched normal or chronic gastritis controls. The
      results suggested that the contamination of gastroscopic equipment played a
      potential role as vehicle causing nosocomial infection of Hp. The risks of Hp
      transmission correlated with times of undertaking endoscopy, especially in the
      elderly.

PMID- 8758420
TI  - [A comparison of purified urease antigen and whole cell antigen of Helicobacter
      pylori by ELISA test--study on the application and serum diagnoses of
      Helicobacter pylori urease diagnostic reagent].
AB  - A useful assay for epidemiological survey of H. pylori infection was reported,
      using the urease antigen of H. pylori to detect the anti-urease antibody in sera
      from 676 patients suffered from gastropathy with ELISA technique, and compared
      with whole cell antigen. Results showed that the purified urease antigen was
      better than whole cell antigen. The partially purified urease antigens rapid
      diagnostic reagent of H. pylori was examined in hospital/institution and compared
      with whole-cell antigens. Results of sera from 676 H. pylori-positive gastritis
      and non-ulcer dyspepsia patients being tested showed that specificity and
      sensitivity of ELISA were 96% and 98% respectively. It seemed to be very useful
      for epidemiological studies on H. pylori infection. The use of ELISA in the
      detection of IgG antibodies against H. pylori was also sensitive, specific and
      rapid in assessing the improvement of both acute and chronic inflammation,
      cleaning of bacteria and the antibody titers after treatment, so as recognized an
      ideal diagnostic method.

PMID- 8758421
TI  - [Epidemiological characteristics of Parkinson's disease in various areas in the
      world].

PMID- 8758423
TI  - [Current status of heart surgery and surgical-therapy of atrial fibrillation in
      China].

PMID- 8758422
TI  - [Intestinal bacterial flora and cancer of the large bowel].

PMID- 8758424
TI  - [Pathological observation and immunohistochemistry study of Type I, III, IV
      collagen in mitral valve and cardiac interstitium of rheumatic disease].
AB  - OBJECTIVES: To examine the pathological base of mitral valve and cardiac
      interstitium of rheumatic disease, and to explore the relationship between Type
      I, and III, IV collagen in mitral and cardiac interstitium of rheumatic heart
      disease. METHODS: HE and ABC method special staining were used to observe the
      mitral valve and cardiac interstitium pathology in 26 case. RESULTS: Diffused
      collagen fibroplasia, hyaline and amyloid degeneration were noted and sometimes
      associated local necrosis and calcification in myocardial interstitium and in
      mitral valve. It was a significant pathologic characteristic of rheumatic heart
      disease. The localization of Type I, III and IV collagen in the valve and
      myocardiac tissues was studied by ABC method of immunohistochemistry. Significant
      fibroplasia of collagen Type I and III was found in the valve, cordae tendon and
      myocardial interstitium of rheumatic heart disease. The composition and secretion
      of collagen Type I and III were expressed not only in fibroblasts but also in
      myocardial cells. CONCLUSIONS: The pathologic foundation of valve and myocardial
      fibrosis is collagen fibroplasia. The degree of fibroplasia is related to the
      repeated reaction of chronic rheumatic inflammation.

PMID- 8758425
TI  - [Preventive effect of gene therapy with pro-uk gene on the formation of intimal
      hyperplasia of vascular anastomotic site].
AB  - OBJECTIVES: To develop a new way to prevent vascular anastomotic sites from
      intimal hyperplasia, we applied medical suture which had been soaked in pN2-pro
      uk plasmid solution to perform rat carotid artery end-to-end anastomosis and
      study the effect of gene therapy with pro-uk gene on the formation of intimal
      hyperplasia of vascular anastomotic sites. METHODS: 11/0 nylon medical suture
      which had been soaked in pN2-pro-uk plasmid solution was applied to perform rat
      carotid artery end to end anastomoses. The rats were randomly divided into
      control and treatment groups. In the control group, medical suture was soaked in
      the pN2 plasmid solution for 72 hours before use. In the treatment group, medical
      suture was soaked in the pN2-pro-uk plasmid solution. By means of Northern blot
      analysis, pro-urokinase activity assay, the number detection of cr-51 labelled
      platelets accumulating at anastomotic sites, 3H-TDR incorporation detection of
      anastomotic sites, pathological changes study, the following results were
      obtained. RESULTS: When isolated RNA was hybridized with the radiolabeled pro-uk
      probe, band appeared in Northern blot analysis in the treatment group, but band
      could not be found in the control group. The pro-uk activity could be detected on
      the 2nd, 7th, 14th, 90th day in the treatment group, but could not be detected in
      the control group. The number of platelets accumulating at the anastomotic sites,
      the average intimal area and 3H-TDR incorporation of anastomotic sites were
      significantly fewer in the treatment group than in the control group (P < 0.01).
      CONCLUSIONS: When medical suture which has been soaked in pN2-pro-uk plasmid
      solution is used to perform vascular anastomoses, the foreign gene can produce
      pro-uk at anastomotic sites and effectively prevent the formation of intimal
      hyperplasia. The mechanism is probably related to the decrease of platelets
      accumulating at anastomotic sites. This study provides a new way to prevent
      vascular anastomotic sites from intimal hyperplasia.

PMID- 8758426
TI  - [K562 cells differentiation induced by RNA from rabbit reticulocytes].
AB  - OBJECTIVE: To study the effect of RNA from the reticulocytes of rabbit on cell
      differentiation of human leukemia cell line K562 cells. METHOD: RNA from rabbit
      reticulocytes and human leukemia K562 cells were cultured for 4 days to detect
      cellular changes. RESULTS: When K562 cells grew in a medium containing 100
      micrograms/ml RNA, the cellular growth and division were gradually suppressed and
      the cells changed toward a differentiated phenotype. Subsequently, K562 cells
      produced hemoglobins and further differentiated terminally. CONCLUSION: RNA of
      mammalian erythrocyte played a role in declining cellular division and growth of
      K562 cells, reversing malignant phenotype, and promoting differentiation.

PMID- 8758427
TI  - [Identification of vertical transmission of hepatitis B virus from mother to
      children by direct sequencing a segment of surface gene of hepatitis B virus].
AB  - SUBJECTIVE: To explore the reason for the failure to interrupt vertical
      transmission of hepatitis B virus (HBV) from mother to children in Chinese
      subjects by vaccination. METHODS: HBV nucleotide sequences isolated from three
      sets of mother/children pairs were analyzed. HBV DNA from the surface antigen
      region encoding the amino acids 101 to 160 of hepatitis B surface antigen (HBsAg)
      was amplified and sequenced from HBsAg positive mother and their children.
      RESULTS: Nucleotide and deduced amino acid sequences were absolutely identical in
      the mother and children in family one and two respectively. However, there were
      five nucleotides different in family one's isolates compared with the family
      two's isolates. All of them were a subtype. In one child of family three, with
      coexisted HBsAg and anti-HBs, sequencing result revealed a point mutation which
      predicted a change from glycine to arginine at residue 145 in the second loop of
      the determinant. The mother and another child had a glycine at this position.
      CONCLUSION: This study revealed the vertical transmission linkage of HBV between
      the mother and children in a molecular level, and also first described a codon
      145 immune escape mutant in Chinese vaccinated children.

PMID- 8758428
TI  - [Confirming the cause of inherited chronic chorea in Chinese patients].
AB  - OBJECTIVE: Huntington's disease (HD, known as inherited chronic chorea in China)
      is an autosomal dominant disorder. Almost all of the cases of inherited chronic
      chorea reported in the chinese literature were sporadic while about one-third of
      the HD families in foreign reports were related. To find out whether the gene
      defect responsible for inherited chronic chorea in Chinese is the same as that
      for Huntington's disease in Caucasians. METHOD: PCR method was employed to
      amplify the (CAG)n repeat sequence of the IT15 gene in normal Chinese and members
      of the families suffering from inherited chronic chorea in Chinese. RESULTS: The
      copy number of the repeats varied from 16 to 26 in 25 normal Chinese and
      increased significantly from 44 to 53 in 7 affected members from 4 families.
      CONCLUSION: It was confirmed for the first time at the gene level that the
      mechanism for inherited chronic chorea in Chinese is the same as that for
      Huntington's disease in Caucasians.

PMID- 8758429
TI  - [Color Doppler in evaluating the effects of octreotide on portal hemodynamics].
AB  - OBJECTIVE: To study the effects of octreotide on portal pressure and the
      relationship between the portal pressure and portal hemodynamics measured by
      color Doppler. METHODS: A high portal resistance model by injecting bletilla
      hyacinthina was established in 6 dogs. The portal pressure and portal
      hemodynamics studied by color Doppler were measured respectively by two
      investigators before and after injecting octreotide into the peripheral vein.
      RESULTS: Portal hypertension was caused by injecting bletilla hyacinthina into
      the portal vein. The portal pressure was reduced and portal venous velocity
      increased after injecting octreotide into the peripheral vein. There was a
      significant negative correlation between the portal pressure and portal venous
      velocity. CONCLUSION: Color Doppler is helpful in evaluating the effects of
      octreotide on the portal pressure.

PMID- 8758430
TI  - [Role of nitric oxide in immunological liver injury in mice].
AB  - OBJECTIVE: To study the role of nitric oxide (NO) in mouse immunological liver
      injury. METHODS: Injection of either bacille calmette gurein (BCG) or
      lipopolysaccharide (LPS) alone in mice was used to induce moderate increase of
      plasma NO level and liver damage were seen after the RESULTS: Administration of
      LPS following BCG injection resulted in remarkable elevation of plasma NO level
      and severe liver damage. The elevation of NO level and liver damage induced by
      BCG or BCG + LPS were not affected by administration of L-arginine, and substrate
      of NO synthase. Inhibition of NO synthase by NG-monomethyl-arginine (NMMA)
      decreased the elevated plasma NO without effect on the elevated plasma GPT and
      GOT levels induced by BCG injection. The BCG + LPS induced elevation of plasma
      GPT and GOT levels were more pronounced after NO production was inhibited by NMMA
      treatment. The action of NMMA mentioned above was partially reversed by
      simultaneous administration of L-arginine. CONCLUSION: NO plays a protective
      action against liver injury induced by BCG + LPS in mice.

PMID- 8758431
TI  - [Detection of minimal disease in bone marrow from non-Hodgkin's lymphoma and its
      clinical significance].
AB  - OBJECTIVE: Using some molecular biological techniques, we studied the clinical
      significance of minimal disease (MD) in bone marrow (BM) from the patients with
      non-Hodgkin's lymphomas (NHL). METHOD: Polymerase chain reaction (PCR) and
      restriction enzymes map analysis of PCR products (PCR/RE) were used to find the
      clonal gene rearrangement of IgH and TCR(gamma) for detecting MD in BM. The BM
      samples from 35 patients with NHL were examined by these techniques. RESULTS: The
      incidences of MD in BM were 66% (23/35), 51% (18/35) in IgH group and 49% (17/35)
      in TCR(gamma) group. While the frequency of BM involvement detected by BM smear
      was 26% (9/35). Not only majority of patients with NHL in this series but also
      above half of patients (7/12) in stage I and II had MD in their BM. MD was
      related to histologic grade and systemic symptoms (P < 0.05). The incidence
      tended to be increased gradually from stage I to stage IV, and these patients
      with MD to be poorer in response rate, mortality and recurrence rate, though
      without statistical significant correlation. CONCLUSIONS: NHL is a systemic
      disease. MD in BM may be a prognostic factor in NHL.

PMID- 8758432
TI  - [The influence of infected mothers on their children's immune response to
      filariasis].
AB  - OBJECTIVES: To investigate the reason for broad clinical spectrum of filariasis
      among the people in the endemic area, and to know the effect of infected mothers
      on their children's immune response to filariasis. METHODS: We measured the
      specific IgG and IgM antibodies in the sera of women and their 1-10 year old
      children, and maternal and umbilical cord, including Mf cases and control
      subjects by using IEST. RESULTS: The positive rates of IgG in the sera of women
      with Mf and their children were 91.4% (53/58) and 65.5% (38/58), and those of the
      control group 28.6% (34/119) and 24.4% (29/119). The positive rates of IgM were
      81.0% (47/58) and 20.7% (12/58), and those the control group 11.8% (14/119) and
      10.9% (13/119), respectively. Also, the positive rates of IgG in the sera of
      women with Mf and their infants were 91.7% (22/24) and 75.0% (18/24), and those
      of the control group 20.2% (19/94) and 16.0% (15/94). The positive rates of IgM
      were 70.8% (17/24) and 8.3% (2/24), and those of the control group 10.6% (10/94)
      and 3.2% (3/94), respectively. CONCLUSIONS: Whether the mother infected with the
      disease or not, the acquired immunological tolerance and resistance to the
      disease in their children might not be affected.

PMID- 8758433
TI  - [Inducing effect of dimethy-4, 4'-dimethoxy-5, 6,5',6-dimethylenedioxybipheny-2,
      2'-dicarboxylate (DDB) on differentiation of leukemia HL-60 cells].
AB  - OBJECTIVE: To study the effects of anti-hepatitis drug, DDB, on leukemia cell
      line HL-60. METHOD: Cytobiological methods were used. RESULT: DDB was inhibited
      the proliferation of HL-60 cells. About 50% of HL-60 cells treated with DDB (10(
      4)mol/L) for 6 days exhibited NBT reduction, and phagocytosis activity was also
      enhanced by DDB (10(-4)mol/L) for 4 days. The HL-60 cells treated with DDB turned
      out to be mature granulocytes morphologically. CONCLUSION: The activity of acid
      phosphatase in DDB-treated HL-60 cells was significantly increased. DDB can
      induce HL-60 cells to differentiate along granulocyte lineage.

PMID- 8758434
TI  - [Anti-embryonation immunity and cultivation of Schistosoma japonicum eggs in
      vitro].
AB  - OBJECTIVE: To study anti-SIEA super-immune sera against the influence on
      schistosoma japonicum in vitro cultivation of newly laid eggs by adult worms,
      their hatches and development. METHODS: The adult worm pairs of Schistosoma
      japonicum were collected from test animals, portae vena which infected with the
      worms for 38-45 days. The worm pairs were injected divided into control group
      with normal rabbit sera and experimental group with anti-SIEA super-immune sera.
      The output of newly laid eggs and the embryonic development were observed with
      immunofluorescence staining. RESULTS: Female worms cultured in vitro with normal
      rabbit serum not only discharged eggs already contained in its uterus, but also
      produced newly formed ones. They however, did not occur in female worms cultured
      with anti-SIEA super-immune sera and the output of eggs by the latter was much
      lower than that of the former. There was also a marked decrease in the proportion
      of developed eggs in the experimental group compared with that in the control
      group. In addition, immunofluorescence staining of immature eggs and female worms
      by anti-SIEA super-immune sera showed that a lightened fluorescence was not only
      seen in the embryonic cells of immature eggs, but also in the vitelaria and in
      the internal membrane tissue of gut cavity of the female worms. CONCLUSION: SIEA
      was possibly involved in the immunity against egg development and fecundity of
      schistosoma japonicum.

PMID- 8758435
TI  - [General principles for ultrasound-guided interventional treatment of liver
      cancer].

PMID- 8758436
TI  - [US-guided microwave in the treatment of liver cancer: experimental study and
      preliminary clinical application].
AB  - OBJECTIVE: To completely coagulate deep tumor and protect normal tissue by using
      microwave electrode is vivo and in vitro animal experimental study, under US
      guided percutaneous microwave coagulation. METHOD: The Ultrasound Microwave
      Therapy-I (UMT-I) equipment was utilized at 2450 MHz in frequency. RESULTS:
      Microwave coagulation could produce a stable necrosis area of 2cm in diameter
      with irradiation at 60-80W for 60-180 seconds, and the corresponding temperature
      at its surrounding area was 61.95 +/- 5.81 degrees C. Microwave induced
      coagulation of tumor correlated well with the sonographic changes. The shape of
      coagulated area was elliptic when 27 mm or 9 mm of the inner conductor of
      electrode was exposed, and the temperature of the shaft of the electrode raised
      smaller and slowly based on our animal experimental study, 15 nodules of 12
      patients with liver cancer were microwave-coagulated under US-guide. The
      temperature of tumor surrounding area raised to 54-69.5 degrees C during
      operation. After treatment, all lesions had smaller size, hypoechogenicity and
      disappearance of blood flow. AFP titer dropped in 7 patients and normalized in 4.
      CONCLUSION: US-guided microwave for the treatment of liver cancer is effective in
      coagulating deep tumor and protecting normal tissue.

PMID- 8758437
TI  - [Application of laparoscopic technique in gastrointestinal surgery].
AB  - OBJECTIVE: To evaluate the feasibility of gastrointestinal procedures guided by
      laparoscopy in 42 patients aged from 18 to 86 years. METHODS: We performed 10
      Billroth II gastrectomies, 10 resections of gastric benign tumor, 11 repairs of
      duodenal perforation, 2 highly selective vagotomies, 5 resections of small bowel,
      3 adhesiolyses of small bowel and 1 ileocolectomy. The operations were performed
      under general anesthesia with endotracheal intubation and through four portals
      (10mm). The omentum and mesentery were mobilized with an electrocautery and
      vessels controlled with either Endoclip or ELC. The reconstructions of the
      digestive tract were performed entirely intraabdominally with ELC. RESULTS:
      Except one patient receiving Billroth II gastrectomy complicated with
      postoperative bleeding had to be reoperated, the remaining 41 patients were
      successfully treated. All the 41 patients could walk and take fluids on the
      second postoperative day. The average length of hospitalization after operation
      was 7.5 days. CONCLUSIONS: Laparoscopic gastrointestinal procedures for selected
      cases can be carried out safely and effectively with decreased postoperative pain
      and rapid recovery. It may change the surgical management of some benign
      gastrointestinal diseases.

PMID- 8758438
TI  - [Anti-tumor effects of bispecific monoclonal antibody targeted human monocytes
      macrophages on hepatoma cells].
AB  - OBJECTIVE: To study anti-tumor affects of bispecific monoclonal antibody targeted
      human monocytes-macrophages on hepatoma cells. METHODS: The fragment of
      monoclonal antibody HAb18F(ab')2 which has high affinity to hepatoma cells and
      the fragment of monoclonal antibody antimonocytes/macrophages MAb7F(ab')2 were
      cross-linked with N-succinimidyl 3-(2-pyridl-dithil) propionate. RESULTS:
      Heteroaggregated monoclonal antibodies HAb18F(ab')2-MAb7F(ab')2 could bind to
      hepatoma cells as well as monocytes-macrophages. They were purified with FPLC
      Sephacryl S-200. The bispecific character was identified with Indirect
      Immunofluorescent Staining. CONCLUSION: In vitro cytotoxicity assay showed that
      HAb18F(ab')2-MAb7F(ab')2 could significantly enhance the lysis of human hepatoma
      cells by human monocytes-macrophages.

PMID- 8758439
TI  - [Experimental study of human micro-urokinase gene therapy].
AB  - OBJECTIVE: To determine the feasibility and efficiency of gene therapy to
      thrombotic disease. METHODS: The retroviral vectors containing 982 bp mUKcDNA
      were constructed and transfected into PA317 viral packaging cells. Recombinant
      retroviral particles collected from media of PA317 cells were injected into mice
      subcutaneous tissue, abdominal cavity and quadriceps muscle, respectively. mUK
      activity of plasma was measured with a synthetic substrate S-2390. Six mice were
      sacrificed after injection for immunofluorohistochemical staining. RESULTS: The
      mUK activity in plasma was obviously increased (P < 0.01) and the expression of
      mUKcDNA was observed at local sites of injection by immunofluorohistochemical
      staining. The mUK activity was raised for 4 months. CONCLUSION: The injection of
      recombinant viral particles containing transcriptional unit of mUKcDNA might be
      applied to the prevention and treatment of thrombotic disease.

PMID- 8758440
TI  - [Role of sensory neuropeptides in the responses of pulmonary and cerebral blood
      vessels to acute hypoxia in rats].
AB  - OBJECTIVE: To study the effects of sensory neuropeptides on pulmonary circulation
      and cerebral blood flow during acute hypoxia in SD rats. METHODS: The changes in
      hypoxic pulmonary vasoconstriction (HPV) and hypoxic cerebral vasodilatation
      (HCVD) were observed in mature SD rats pretreated with capsaicin (50 mg/kg) when
      they were newborn. The hypoxic changes of plasma substance P in the pulmonary
      circulation and the peptidergic nerve fibers in the lungs were determined with
      radioimmunoassay and immunohistochemical staining respectively. The effects of
      exogenous SP on HPV and HCVD were studied as well. RESULTS: The mean pulmonary
      artery pressure (2.46 +/- 0.07kPa), pulmonary vascular resistance (3665.09 +/-
      164.08kPa.s/L) and the percentage change of pulmonary vascular resistance (delta
      PVR%) during hypoxia (98.67% +/- 4.07%) in group capsaicin (Caps) were higher
      than those in group Veh (vehicle control) (2.22 +/- 0.04 kPa, 2945.14 +/-
      119.23kPa.s/L and 41.21% +/- 2.08% respectively) (t = 2.89, 3.49 and 12.18, P <
      0.01) and those in group NC (normal control) (2.22 +/- 0.03 kPa, 2908.19 +/-
      130.85 kPa.s/L and 39.13% +/- 1.48%) (t = 3.09, 3.59 and 13.48, P < 0.01). The
      wave amplitude in rheoencephalogram (H) in group Caps (11.27 +/- 1.02 m omega)
      was less than those in group Veh (14.96 +/- 1.08 m omega) (t = 2.49, P < 0.05)
      and group NC (15.86 +/- 1.33 m omega) (t = 2.69, P < 0.05) during normoxia. It
      increased significantly in groups Veh (41.36% +/- 6.74%) (t = 9.44, P < 0.01) and
      NC (48.79 +/- 6.10%) (t = 11.21, P < 0.01) during acute hypoxia, however it
      dropped in group Caps (-23.55 +/- 2.38%). The plasma SP-like immunoreactivity
      level in the outflow blood of pulmonary circulation increased in hypoxic rats
      (SPop-SPip = 139.04 +/- 27.97 pmol/L) while it decreased in group Caps (SPop-SPip
      = -45.84 +/- 6.52 pmol/L) (t = 5.41, P < 0.01). The SP- and CGRP-immunoreactive
      fibers in lungs appeared to be sparser and thinner during hypoxic inspiration for
      3-5 min. SP decreased delta PVR% from 47.42% +/- 4.70% to 20.58% +/- 2.66% (t =
      6.84, P < 0.01) while it increased delta H% from 12.51% +/- 4.31% to 37.66% +/-
      5.17% (t = 3.93, P < 0.01) during hypoxia. CONCLUSIONS: Sensory neuropeptides
      might contribute to the modulation of the basic tone of pulmonary and cerebral
      vessels. They could be released during acute hypoxia modulating HPV and mediating
      HCVD.

PMID- 8758441
TI  - [Inhibitory effects of antisense oligonucleotides delivered locally via hydrogel
      catheter on myointimal hyperplasia of rat carotid artery after nitrogen drying].
AB  - OBJECTIVE: To determine if antisense c-myb delivered locally via the hydrogel
      catheter inhibits the development of myointimal hyperplasia in rat carotid artery
      after nitrogen desiccation of the endothelium. METHODS: Forty rats were
      randomized into four groups (ten in each). After endothelial injury, different
      oligonucleotides were administered locally through the hydrogel catheter. Animals
      were killed at 14 days following gas drying. The lumen areas, ratios of intimal
      to medial areas and intimal to medial thickness were measured with the aid of
      computer. The q test was used for statistical analysis. RESULTS: The lumen area
      of antisense c-myb group (0.29 +/- 0.01 mm2) was larger than that of sense and
      mismatch groups (0.17 +/- 0.05 mm2, q = 4.1729; 0.18 +/- 0.05 mm2, q = 3.7489, P
      < 0.05), and less than that of control group (0.40 +/- 0.14, q = 3.7782, P <
      0.05). The ratios of intimal to medial areas and intimal to medial thickness for
      antisense c-myb group (0.45 +/- 0.24, 0.57 +/- 0.24) were significantly decreased
      compared with sense and mismatch groups (1.26 +/- 0.25, q = 9.8913; 1.16 +/-
      0.38, q = 8.4252; 2.15 +/- 0.85, q = 8.6850; 1.85 +/- 0.79, q = 6.8389, P <
      0.01). CONCLUSIONS: Myointimal hyperplasia of rat carotid artery after nitrogen
      drying can be markedly suppressed by intravascular local delivery of synthetic
      antisense c-myb via hydrogel catheter. The technique is a promising to prevent
      artery from obstructive stenosis.

PMID- 8758442
TI  - [Modulation of bcl-2 antisense RNA on programmed cell death of leukemic cell
      line].
AB  - OBJECTIVE: To investigate modulation of decrease of intrinsic bcl-2 protein
      levels on programmed cell death of leukemia cells. METHOD: Gene transfection
      procedure was applied to observe the effect of antisense RNA-mediated suppression
      of bcl-2 gene expression on programmed cell death of human T-lymphocytic leukemia
      cell line CEM. RESULTS: Temporary expression of antisense bcl-2 gene could
      effectively reduce levels of intrinsic bcl-2 protein of CEM cells and render it
      more sensitive to etoposide-induced cytotoxicity. Moreover, a great deal of
      apoptotic bodies and ladder DNA was always produced during etoposide-mediated
      killing of CEM and when CEM expressing bcl-2 antisense RNA served as target cells
      in particular, the amount of ladder DNA increased to around 40%. CONCLUSION:
      Programmed cell death is one of the mechanisms by which etoposide kills leukemic
      cells and is modulated by cellular intrinsic bcl-2 protein.

PMID- 8758443
TI  - [Glutamine dipeptide enriched nutritional solutions attenuate bacterial
      translocation in rats after 60% intestinal resections].
AB  - OBJECTIVE: To investigate the effects of alanyl-glutamine dipeptide (Ala-Gln)
      enriched parenteral nutrition solution on intestinal mucosa or gut barrier since
      traditional parenteral nutrition leads to bacterial translocation. METHODS: The
      moderate operation stress was induced by 60% resection of small intestine.
      Qualified rats distributed in three groups: Chow group (n = 10) received standard
      rat chow, PN group (n = 10) received traditional parenteral nutrition solution
      only, and Ala-Gln group (n = 10) received glutamine dipeptide enriched
      nutritional solutions (3% Ala-Gln). Rats were maintained on their respective
      diets for 7 days. RESULTS: Chow group and Ala-Gln group maintained serum
      glutamine concentration, villus height and mucosal thickness. The bacterial
      translocation rate in Chow group and Ala-Gln group was 20% and in PN group 70%.
      CONCLUSION: Results demonstrate that Ala-Gln enriched nutritional solutions
      maintain intestinal adaptation and gut barrier function after massive intestinal
      resection.

PMID- 8758444
TI  - [Effect of platelet activating factor receptor at spinal cord neurocyte membrane
      on secondary damage after spinal cord injury].
AB  - OBJECTIVE: To investigate the effects of platelet activating factor (PAF)
      receptor and its antagonist on secondary damage after spinal cord injury.
      METHODS: We extracted spinal cord neurocyte membrane protein in cats by improved
      Domigo method. The specific binding sites of PAF were measured by 3H-PAF
      radioligand binding test. RESULTS: There were both high affinity binding sites
      and low affinity binding sites of PAF on spinal cord neurocyte membrane. The Kd1,
      Bmax1, Kd2 and Bmax2 of PAF receptor on spinal cord neurocyte membrane at 2, 6
      hours and 1 week after trauma significantly decreased as compared to sham
      operated control group (P < 0.01). PAF receptor antagonist BN52021 could reduced
      water content and Even's blue content of injured spinal cord tissue, also improve
      pathological change of spinal cord tissue after trauma. CONCLUSIONS: PAF receptor
      plays an important role in inducing pathophysiological process of secondary
      damage after trauma. PAF receptor antagonist can effectively prevent and treat
      secondary damage after trauma.

PMID- 8758445
TI  - [Study on asialoglycoprotein receptor mediated endocytosis of antiviral
      conjugate].
AB  - OBJECTIVE: To observe the internalization process of asialoglycoprotein receptor
      mediated antiviral conjugate lactosaminated human albumin arabinoside adenine
      monophosphate (L-HSA-Ara-AMP) in human hepatoma cell line HepG-2, and provide the
      specificity and practicability of receptor targeting treatment of viral
      hepatitis. METHODS: Colloidal gold labelling technique combined with
      electronmicroscopic observation was employed. The study was carried out in three
      groups: experiment group (the internalization of antiviral conjugate in HepG-2
      cell line), positive control group (lactosaminated human serum albumin), and
      negative control group and (human serum albumin). RESULTS: L-HSA-Ara-AMP can be
      specially recognized and uptaken by the cells and enter the cells via coated pit.
      After internalization, the antiviral conjugate entered the lysosome ultimately.
      CONCLUSIONS: The therapy of asialoglycoprotein receptor targeting treatment of
      viral hepatitis has a high specificity. The therapy is worth further study.

PMID- 8758446
TI  - [Ultrastructural and immunohistochemical localization of endothelin-1 in
      nonneoplastic, hyperplastic and neoplastic adrenal gland].
AB  - OBJECTIVE: To determine the ET-1 immunoreactivity in human nonneoplastic,
      hyperplastic and neoplastic adrenal gland ultrastructurally and histologically.
      METHODS: Sensitive immunohistochemical technique was used. RESULTS: The ET-1
      immunoreactivity was found in non-neoplastic (100%), adrenal cortical adenoma
      (100%) and cortical carcinoma (3/10). ET-1 immunoreactivity was regularly seen in
      the cortex, especially in zona fasciculata and to a varying extent also in the
      other two zones, but not in the medulla. The immunoreactive material in the
      cytoplasm was mostly in vacuolar or grain-like structures. Focally, cell membrane
      also showed immunoreactive staining. Most cortical adenomas displayed numerous
      immunoreactive cells. The immunoreactivity in the tumor tissue was in the same
      forms as in normal cortex, but the reactive products were generally few. No
      obvious differences in immunostaining were seen between the aldosterone- and
      cortisol-producing adenomas or the non-functioning ones. Three of the ten
      carcinomas contained immunoreactive cells, but they were few and appeared
      focally. The ET-1 immunoreactive structures were seen as "dust-like" material.
      Electronmicroscopical investigation revealed ET-1 immunoreactive products
      adjacent to the outer surface of the membrane of lipid bodies, in mitochondria,
      rough endoplasmic reticulum and focally on the cell membrane, but no
      immunolabelling was seen in the medulla. CONCLUSIONS: The localization of ET-1 in
      the endoplasmic reticulum indicates that this peptide is synthesized in the
      cortical cells. The localization in the membrane of the lipid bodies and in the
      mitochondria indicates that it may take part in steroid synthesis. The focally
      immunolabelled cell membranes may depend on ET-1 bond to ET receptors. The
      difference in immunoreactivity between the benign and the malignant cortical
      neoplasms may be of diagnostic value.

PMID- 8758447
TI  - [The effect of nimodipine and papaverine on delayed cerebral vasospasm in dogs].
AB  - OBJECTIVE: To evaluate the effect of nimodipine and papaverine (Pap) on the
      spastic arteries with delayed cerebral vasospasm (DCVS) in dogs. METHODS: A model
      of DCVS in dogs was induced by the cisterna magna injections of fresh autologous
      blood twice. The diameter of the basilar arteries with and without DCVS was
      measured with the aid of a JVC operative microes cope in vivo after nimodipine
      and Pap were directly placed around the arteries. RESULTS: The dilation of the
      basilar arteries was obviously induced by application of nimodipine and Pap in
      the dogs without DCVS no dilation was induced by application of nimodipine and
      slight dilation by application of Pap but in those with DCVS. CONCLUSION: The
      cerebral blood flow is improved by the effect of nimodipine on non-spastic
      arteries. Pap has been found to reverse slightly the narrowing of the basilar
      arteries with DCVS and to dilate the arteries without DCVS, but the vasodilation
      effect is transient.

PMID- 8758448
TI  - [Ion-selective microelectrodes: principle and application of in vivo measurements
      of ionic concentrations in cochlear endolymph].
AB  - OBJECTIVE: To introduce the method of making neutral carrier ion-selective
      microelectrode and use it for in vivo measurement of ionic concentrations in
      cochloear endolymph. METHODS: GG-17 glass capillaries with 1.85 mm O.D. were
      rinsed extensively and dried in an oven. Two capillaries were parallelly
      connected and pulled with microelectrode puller to make a double-barreled
      micropipette. One barrel was back-filled with ion exchanger and internal
      reference solution, which served as ionic potential electrode, while the other
      barrel filled with 150 mmol/L KCL as reference electrode. Each barrel of
      microelectrode was connected to differential electrometer via Ag-AgCl wire and
      output was recorded on a three-channel recorder. Every ion-selective
      microelectrode was calibrated in a series of standard solutions to determine the
      required characteristics. Twenty healthy guinea pigs with normal hearing were
      anesthetized and were artificially respired through the tracheal canal after the
      intramuscular injection of suxamethonium chloride. The tympanic bulla was exposed
      and a double-barreled ion-selective electrode was inserted into the scala media
      through the round window and basilar membrane. The ionic potentials and
      endocochlear potentials (EP) were simultaneously recorded from the basal turn of
      the cochlea. Ionic concentrations were then calculated by Nicolsky-Eisenman
      equation. RESULTS: The concentrations of potassium, sodium and calcium ions in
      the cochlear endolymph were 146.3 +/- 11.8 mmol/L, 0.36 +/- 0.22 mmol/L and 16.2
      +/- 5.7 micromol/L, respectively. CONCLUSIONS: The neutral carrier ion-selective
      microelectrode made with the above method is reliable and therefore can be used
      for accurately measuring the ionic concentrations of microenvironment in vivo
      continuously and transiently.

PMID- 8758449
TI  - [Grouping and typing of Ureaplasma urealyticum].
AB  - OBJECTIVE: To construct the molecular biological methods to group and type
      Ureaplasma urealyticum. METHOD: Polymerase chain reaction was used to detect and
      group the 14 standard serotypes of Ureaplasma urealyticum. 272 urogenital tract
      clinical samples were detected and grouped. Random amplified polymorphic
      deoxyribose nucleic acid was used to study and compare Ureaplasma urealyticum
      serotypes 1, 3, 6, 14, 8, 10, 11. RESULTS: Detected by the polymerase chain
      reaction, group 1 had 403 bp amplified fragments, and group 2 had 448 bp
      amplified fragments. 272 urogenital tract clinical samples were detected. 72
      cases were positive for ureaplasma urealyticum, 69 were positive for group 1, and
      3 were positive for group 2. Random amplified polymorphic deoxyribose nucleic
      acid was used and gene fingerprinting maps of ureaplasma urealyticum serotypes 1,
      3, 6, 14, 8, 10, 11 were constructed. CONCLUSIONS: Ureaplasma urealyticum
      grouping method was constructed by polymerase chain reaction. Among the
      urogenital tract clinical samples positive for Ureaplasma urealyticum, group 1
      was more common to be positive. Random amplified polymorphic deoxyribose nucleic
      acid can be used as typing method of Ureaplasma urealyticum.

PMID- 8758450
TI  - [Clinical study of scopolamine detoxification for the treatment of heroin
      addicts].
AB  - OBJECTIVE: To evaluate the efficacy of treatment of heroin addicts (n = 100) by
      scopolamine detoxification (10 days program). METHODS: Methadone detoxification
      (10 days program) group (n = 50) and clonidine treated group (n = 50) served as
      controls. RESULTS: The scores of abstinence syndrome in scopolamine
      detoxification group were lower that those in clonidine treated group in the
      first three days of protocol, but this difference disappeared in the late stage
      of treatment. While scopolamine detoxification was effective as methadone
      detoxification in the control of abstinence syndrome during the first five days
      of treatment but the difference in the scores of abstinence syndrome between
      scopolamine and methadone group was observed during the late five days of
      protocol. The side-effects produced by scopolamine in general were dry mouth,
      somnolence, tachycardia, blurred vision and so on, which relieved gradually or
      disappeared with decreasing of its doses. CONCLUSION: Scopolamine does not result
      in potential dependence and has definite curative effect in the treatment of
      heroin addiction.

PMID- 8758452
TI  - [Improving the diagnosis and treatment of ischemic necrosis of femoral head].

PMID- 8758451
TI  - [Advances in the study of proto-oncogene c-erbB-2].

PMID- 8758453
TI  - [Proper evaluation and uses of quinolone antibiotics].

PMID- 8758454
TI  - [Serological diagnosis of viral hepatitis E].

PMID- 8758455
TI  - [Prevention and treatment effect of niacin on FES: experimental study].
AB  - OBJECTIVE: On the basis of fat embolism syndrome animal model injected with
      homologous dog bone marrow fat, we probed into the prevention and treatment
      effect of niacin on FES. METHODS: Fourteen dogs were divided into experimental
      group and control group. In the experimental group, the dogs were injected with
      homologous dog bone marrow fat accompanied by niacin injection 4 mg/kg. 8 hr
      intravenously for 48 hours, while in the control group, only bone marrow fat was
      injected. PaO2, FFA, triglyceride, platelet counts, fat drops in the blood clots
      of vein were examined at different times. Finally, morphology and pathology of
      the lungs were observed. RESULTS: There were a slower decrease in PaO2 and
      platelet counts and no obvious increase in triglycerides and FFA in the
      experimental group. The amount and diameter of fat drops in the blood clots of
      vein and in the lungs were less in the experimental group than in the control.
      Pathological examinations of the lungs demonstrated much less injuries in the
      experimental group. CONCLUSION: Good prevention and treatment effect of niacin on
      fat embolism syndrome is suggested.

PMID- 8758456
TI  - [Using a lipid clearing drug to prevent osteocytes damage of the femoral head in
      steroid-treated rabbits].
AB  - OBJECTIVE: We investigated experimentally the prevention of steroid-induced
      osteonecrosis of the femoral head. METHODS: Twenty-three rabbits were divided
      into three groups: (Group S) steroid treated, (Group T), steroid and clofibrate
      treated, and controls. Serological tests (cholesterol and triglyceride),
      histology and histochemical studies and electron microscopic examination were
      performed six weeks after treatment. RESULTS: The serum cholesterol and TG levels
      increased obviously in Group S. Although Group T animals also showed
      hyperlipidemia, their serum cholesterol and TG levels were much lower than those
      for Group S. Group S animals demonstrated fatty degeneration of the liver. Lipid
      droplets were seen in the osteocytes of the femoral heads of these animals, which
      compressed the nucleus of the osteocytes along with nuclear pyknosis or absent
      nuclei. However, the construction of liver cells and osteocytes of the femoral
      head were almost normal in Group T. Lipid containing osteocytes were not seen in
      these animals. CONCLUSION: These observations demonstrated that clofibrate
      decreased hyperlipidaemia, modified lipid metabolism, and diminished steroid
      induced damage to the osteocytes. This finding may be a guide to protect against
      steroid-induced osteonecrosis of the femoral head.

PMID- 8758457
TI  - [Transplantation of pedicled pisiform bone to replace lunate bone with aseptic
      necrosis].
AB  - OBJECTIVE: To find out a new and effective method for the treatment of aseptic
      necrosis of lunate bone. METHODS: Blood supply and morphology of pisiform bone
      were investigated in 25 upper limbs and 57 sets of carpal bone from adult
      cadavers on the basis of anatomical study. The lunate bone was replaced with
      pisiform bone of pedicled blood vessel and tendon of musculus flexor earpiulnaris
      in 17 patients with aseptic necrosis of lunate bone (stage III). RESULTS: The
      patients were followed up for 18-46 months (average of 28 months). Complete
      relief of pain was obtained in all of the patients, and the range of motion of
      their wrists was improved. Grip strength was increased by 48.2%. Radiograph
      showed normal location of transferred pisiform bone without osteosclerosis and
      atrophy in 16 patients. Atrophy of pisiform bone was found 2 years after
      operation in one patient. In the 17 patients, 15 resumed their original jobs and
      2 changed their jobs for other reasons. CONCLUSION: We consider that the carpal
      bone chain can be completely preserved by transplantation of pedicled pisiform
      bone, which it is an effective method to treat aseptic necrosis stage III of
      lunate bone.

PMID- 8758458
TI  - [HP8: the partial cDNA clone of a novel member of C/EBP gene family].
AB  - OBJECTIVE: To explore the human C/EBP related genes. METHODS: Screening human
      placenta cDNA library with rat C/EBP cDNA probe. RESULTS: One positive clone, HP8
      was obtained. This clone contained 1975 base pairs which include 604 coding base
      pairs. The matched DNA sequence was not found in the gene database (EMBL 95.6).
      The 201 amino acids encoded by this gene had the leucine zipper structure and
      demonstrated the highest homology (97%) with C/EBP throughout the DNA-binding
      domain and leucine repeat region (C-terminal 60 amino acids). Beyond this region,
      only low homology was detected in HP8 protein and C/EBP or C/EBP related
      proteins. Herewith, HP8 was defined as a novel member of C/EBP gene family.
      Genomic Southern blot analysis confirmed that HP8 was a single copy gene.
      Northern blot analysis in 14 different fetus tissues showed that high level of
      HP8 mRNA was expressed in small intestine and skin, middle level in adrenal
      gland, low level in liver, lung, kidney, thyroid gland and gallbladder. In 3
      human adult liver tissues, only one low level HP8 mRNA, whereas of 5 hepatomas
      and one of their surrounding nontumorous hepatic tissues had, high level HP8
      mRNA. CONCLUSION: These results suggested that HP8 gene might be a transactivator
      related to cell growth. As Northern blot analysis indicated, HP8 gene has about
      2.7 Kb full length cDNA.

PMID- 8758459
TI  - [The incidence of hypertension and associated factors in 10 population groups of
      China].
AB  - OBJECTIVE: To study the natural populations studied including 3 groups of
      workers, 6 groups of farmers and 1 group of fishermen, distributed in
      Heilongjiang, Hebei, Shanxi, Shannxi, Jiangsu and Zhejiang provinces and Guangxi
      Autonomous Region. METHODS: In 1982-1985, a total of 25656 persons (male 13,390,
      female 12,266) aged 35-59 were surveyed for the risk factors of cardiovascular
      diseases. RESULTS: 20641 (male 10584, female 10057) of them were re-examined in
      1988-1989, giving a response rate of 80.5%. During the 5 year follow-up period,
      the incidence of definite hypertension was 1.20% (male) and 1.07% (female), with
      the borderline plus definite rates being 3.27% and 2.68% per year, respectively.
      The incidence varied from 0.76% to 5.62% per year for borderline plus definite.
      The incidence was higher in the north than in the south, higher in farmers than
      in workers, and lowest in fishermen. The incidence rates were higher in men than
      in women, and the older the age, the higher the incidence of hypertension. Both
      univariate and logistic regression indicated that the main risk factors of
      hypertension are the levels of baseline systolic and diastolic blood pressure,
      BMI, and alcohol intake, all of which showed a dose-response relation to the
      incidence rate of hypertension. These relationships were affected by age; the
      younger, the more marked the increase of relative risk (RR) with risk factor
      levels. After adjusting for age, sex and location by logistic regression, with
      every 10 mmHg increase of SBP or DBP within the normotensive range, or every 1
      unit increase of BMI, the RR of hypertension was -- estimated to increase by
      71.5%, 102.4% and 10.8%, respectively. No significant relationship was found
      between the level of serum cholesterol and the incidence of hypertension, but
      persons with faster heart rates showed a higher RR. CONCLUSION: Primary
      prevention of hypertension in persons should be started before age of 35 years.

PMID- 8758460
TI  - [Inhibition of genomic HDV ribozyme activity by antisense oligodeoxynucleotides].
AB  - OBJECTIVE: To study inhibitory effect of antisense oligodeoxynucleotides (asODNs)
      on genomic HDV ribozyme activity. METHODS: Plasmid pHDVrz277 used to transcribe a
      112 nucleotides (nt) genomic HDV ribozyme constructed earlier in our laboratory.
      It had genomic and antigenomic HDV ribozyme sequences from 665-941nt. The
      inhibitory effect of five asODNs on genomic HDV ribozyme activity was studied to
      select the potential effective sequences in vitro. RESULTS: The results showed
      that asODN, being complementary to 683-703nt (stem I and self-cleavage site),
      completely blocked the activity of a 112nt genomic HDV ribozyme transcription in
      vitro. The inhibition rate of asODNs against 756-770nt (SSrB) and 721-735nt
      (SSrA) were 69.36% and 48.64% respectively. However, two asODNs covered the 736
      750nt (stem IV) and 704-720nt (SSrC) showed almost no inhibitory effect on
      genomic HDV ribozyme. Fine sequence specificity testing at region 683-703nt
      revealed that asODN as small as 13 nt flanking the self-cleavage site (683-695nt)
      retained a high inhibition rate (> 90%). CONCLUSION: The results suggested that
      stem I and SSrB may play an important role in genomic HDV ribozyme and asODNs can
      block genomic HDV ribozyme activity almost completely.

PMID- 8758462
TI  - [Heparin-free hemodialysis of hemophan adsorption: an experimental study].
AB  - OBJECTIVE: To demonstrate the adsorption of heparin by hemophan and investigate
      the related factors influencing the adsorbent quantity in attempting to provide
      theoretical evidence for the clinical application of heparin-free hemodialysis.
      METHODS: The amount of heparin adsorbed by hemophan was obtained by calculating
      the decrease of heparin concentration before and after circulated in the dialyzer
      for 25 minutes. Heparin concentration in the circulating solution was measured by
      using HPLC. In addition, samples taken from the naturally dried hemophan dialyzer
      were also undergone X-ray photoelectronic spectrometric analysis. The adsorption
      time and the dosage of heparin were considered as factors influencing the amount
      of heparin adsorption. RESULTS: A special sulfur peak occurred in the samples
      taken from heparin circulated hemophan dialyzer, while it did not appear in
      unused control, demonstrated that the hemophan membrane had a good capacity to
      adsorbed heparin. The mean adsorbent values in new dialyzer and those reused one
      or twice were 31.9 mg and 40.6 mg respectively. The adsorbent quantity was
      increased as the dose of heparin and adsorption time were increased. CONCLUSION:
      The hemophan membrane is able to adsorb heparin, thus bring forth strong evidence
      for the clinical application of heparin-free hemodialysis.

PMID- 8758461
TI  - [Enhancing immunogenicity of pres antigen of hepatitis B virus by fusing
      genetically it with interleukin-2].
AB  - OBJECTIVE: To combine the bioactivities of human interleukin-2 (IL-2) with entire
      preS antigen of hepatitis B virus (HBV), and search for specific
      immunotherapeutic agent against chronic hepatitis B. METHODS: A chimeric gene
      composed of preS gene from HBV DNA and human IL-2 cDNA was constructed by using
      polymerase chain reaction and genetic engineering methods, and a novel type of
      chimeric protein (IL-2-preS) was expressed with high efficiency in E. coli
      transformed by the chimeric gene clone. RESULTS: It was confirmed that the
      chimeric protein retained the full bioactivities of natural IL-2 and preS
      molecules, such as maintaining CTLL cells to proliferate, with the specific
      activity being about 10(7)u/mg protein, and binding with monoclonal antibodies
      against preS1 and preS2 and polymerized human serum albumin (PHSA), etc. It was
      shown that the titer of antibody against preS antigen in mice induced by IL-2
      preS was 9, 11 and 13 times more than those induced by a mixture of IL-2 with
      preS antigen, MS-2-preS chimeric protein and preS antigen alone, respectively.
      CONCLUSION: IL-2-preS potentiates immunogenecity of preS antigen and enhances
      immune responses of human bodies against preS antigen. In addition, IL-2-preS is
      of double targetting effect in human bodies, and may be used as a new generation
      of immunotherapeutic agent for chronic hepatitis B and hepatocellular carcinoma.

PMID- 8758463
TI  - [Effects of insulin and captopril on growth of glomerular mesangial cells in STZ
      induced diabetic rats].
AB  - OBJECTIVE: To observe the effects of insulin and captopril on growth of mesangial
      cells and on production of interleukin-6 (IL-6) and tumor necrosis factor (TNF)
      in culture media of glomerular cells. METHOD: Streptozocin induced diabetic rats
      (DM rats) were compared with normal wistar rats. RESULTS: The CPM value of 3H-TdR
      incorporated into mesangial cells in DM rats was significantly higher than that
      in Wistar rats. When the culture media was added by 5 x 10(-4) U/ml, 5 x 10(-3)
      U/ml and 5 x 10(-1) U/ml of insulin, the CPM value incorporated into mesangial
      cells and the concentration of IL-6 in the culture media of both DM and wistar
      rats were significantly higher than those of the control (no insulin). When
      captopril (10(-6) mol/L, 10(-4) mol/L, 10(-3) mol/L) was added into the media in
      different concentration, the cpm value of 3H-TdR and the concentration of TNF in
      DM rats were significantly lower than those of the control (no captopril). But
      the CPM value of 3H-TdR in Wistar rats was lower than that in the control, which
      was only seen in the concentration of 10(-3)M captopril. CONCLUSION: Ins could
      promote 3H-TdR in corporation and increase the production of IL-6, and captopril
      inhibited 3H-TdR in corporation and decrease the production of TNF.

PMID- 8758465
TI  - [Altitude medicine].

PMID- 8758464
TI  - [Effects of ACM sequential chemotherapy on ovarian function in trophoblastic
      tumors].
AB  - OBJECTIVE: To study the changes of ovarian function during and after ACM
      sequential chemotherapy on trophoblastic tumors. METHODS: 17 patients with
      trophoblastic tumors, received totally 48 cycles of ACM chemotherapy. Of these, 7
      underwent hysterotomy and focal ectomy and ovarian biopsy. Changes of
      menstruation and BBT were observed. beta-hCG, E2, FSH and LH were assayed and
      histological and immunohistochemical studies in ovaries biopsied were made.
      RESULTS: Amenorrhea and anovulatory BBT were predominant at the onset of
      chemotherapy and high level of beta-hCG. Following chemotherapy and decrease of
      beta-hCG, menstruation recovered with less amount and BBT transformed into
      ovulatory types with shorter luteal phase. The E2 level appeared to be lower and
      the FSH and LH level higher. The different kinds of follicles were decreased, but
      estrogen receptors unchanged. Follow-up showed that ovarian function of 12 of the
      17 patients returned to normal in one year. CONCLUSION: ACM chemotherapy
      suppresses ovarian function mildly and temporarily. Trophoblastic tumor also
      affects ovarian function. ACM chemotherapy seems to be suitable for young
      patients with trophoblastic tumors who desire child-bearing.

PMID- 8758466
TI  - [Aviation medicine].

PMID- 8758467
TI  - [Naval medicine].

PMID- 8758468
TI  - [Social medicine].

PMID- 8758469
TI  - [Comparison of the activity of beta-lactams against Pseudomonas aeruginosa
      according to phenotypes of resistance].
AB  - The in vitro activity of ticarcillin, ticarcillin-clavulanic acid, piperacillin,
      piperacillin-tazobactam, cefsulodin, ceftazidime, cefepime, cefpirome and
      aztreonam was evaluated against 130 isolates of Pseudomonas aeruginosa with
      various beta-lactam phenotypes. MICs were determined by the agar dilution method
      and inhibition method and inhibition zones by the disk test. The resistance
      mechanisms were characterized by the iodometric method. The activity of cefepime
      was greater than that of cefpirome whatever the resistance phenotype. Some
      ticarcillin-susceptible strains were intermediate to cefepime and cefpirome. Most
      strains with a penicillinase or "intrinsic resistance" phenotype were susceptible
      to ceftazidime but intermediate to cefepime and cefpirome. Only 10% of
      cephalosporinase-over-producing strains remained susceptible to cefepime.

PMID- 8758470
TI  - [In vitro activity of a new fluoroquinolone, marbofloxacin (RO 09-1168) against
      strictly anaerobic bacteria and some bacteria from human fecal flora].
AB  - As recommended by the EEC, the in vitro activity of a veterinary quinolone has to
      be evaluated on human strains isolated from the gut and especially against
      anaerobes. Thus, the MICs for Marbofloxacin were determined by the reference agar
      method (Norma NCCLS M11 A3) using Wilkins Chalgren medium for the 124 anaerobic
      strains and Mueller Hinton agar for E. coli, Proteus, Enterococcus and
      Lactobacillus. On the whole aerobes, the activity of Marbofloxacin was equal or
      slightly greater to that of ofloxacin. The modal MIC was 0.03 mg/l for
      Enterobacteriaceae, 2 mg/l and 16 mg/l for Enterococcus and Lactobacillus
      strains, respectively. Considering the anti-anaerobic activity of this new drug,
      in comparison with that of ofloxacin, MICs for ofloxacin were generally one log2
      higher for Gram negative bacilli and two log2 higher for Gram positive bacilli.
      Modal MICs for marbofloxacin were 0.12 mg/l for Clostridium perfringens, 0.5 mg/l
      for Bacteroides fragilis, Fusobacterium, Prevotella, and Peptostreptococcus
      strains, 1 mg/l for Bifidobacteria, 2 mg/l for non-fragilis members of the B.
      fragilis group, and 4 mg/l for C. difficile strains, respectively. It appears in
      vitro that Marbofloxacin was a more potent agent than ofloxacin on the whole
      anaerobes.

PMID- 8758471
TI  - [In vitro study of the bacteriostatic and bactericidal activity of meropenem
      against strains of Pseudomonas aeruginosa multiresistant to antibiotics].
AB  - Meropenem is a new dehydropeptidase stable carbapenem which has an in vitro
      bacteriostatic activity superior to imipenem against Pseudomonas aeruginosa.
      Minimal inhibitory concentrations of meropenem (MEM) and imipenem (IPM) were
      determined on twelve strains: two were genetically characterized reference
      strains and ten isolated from patients. Killing curves were performed for MEM
      used at 1,2 and 4 fold the MIC and 32 mg/l; survivors were counted at baseline
      and after 5 and 24 hours of incubation by spiral plating. Five strains were
      susceptible to MEM and IPM; five were intermediate and two resistant to MEM;
      these seven strains were resistant to IPM. A weak bactericidal effect was
      obtained after 5 h at each concentration. Only one strain achieved a 3 log 10
      reduction after 5 h at 2 x MIC. A regrowth of all the strains tested was observed
      after 24 h.

PMID- 8758472
TI  - [In vitro susceptibility of Pasteurella and related bacteria to five orally
      administered antibiotics].
AB  - Tetracyclines and beta-lactam antibiotics are usually recommended for the
      treatment of pasteurellosis following bite wounds. However other oral
      antimicrobial agents could be proposed. In vitro susceptibility of 94 Pasteurella
      strains [P. multocida (79), P. stomatis (11), P. dagmatis (2), P. canis (1), P.
      "SP" (1)], 20 group EF-4 strains and 28 Neisseria weaveri strains (formerly group
      M-5), that are bacteria often isolated after animal-inflicted wounds, was studied
      towards five antibiotics: clarithromycin, azithromycin, pristinamycin,
      trimethoprim-sulfamethoxazole and ciprofloxacin. MICs were determined by the agar
      dilution method using HTM medium (Oxoid), and for pristinamycin using both HTM
      and Mueller-Hinton agar supplemented with 5% horse blood (BMH). Most of
      Pasteurella isolates showed intermediate susceptibility to clarithromycin (63%)
      and to azithromycin (90.5%) with lower MICs for azithromycin. Fourty-two and
      thirty-two percent of Pasteurella strains were susceptible to pristinamycin
      respectively on HTM and on BMH. EF-4 and N. weaveri were more sensitive than
      Pasteurella to macrolides and to pristinamycin. Trimethoprim-sulfamethoxazole was
      active against all isolates, with higher MICs for EF-4 and N. weaveri. On all
      strains tested, the lowest MICs were observed for ciprofloxacin. Trimethoprim
      sulfamethoxazole and ciprofloxacin could be proposed as a therapeutic alternative
      in case of pasteurellosis following animal bites.

PMID- 8758473
TI  - [Comparative study of minimal inhibiting concentrations of doxycycline, ofloxacin
      and erythromycin against 18 recent isolates from Chlamydia trachomatis (1994
      1995)].
AB  - In vitro activity of the 3 antimicrobial agents, against 18 recent isolates of
      Chlamydia trachomatis: 11 from urethral samples and 7 from endocervical samples,
      was tested by cell culture technique. HeLa 229 cells maintained in antibiotic
      free MEM medium supplemented with 10% fetal calf serum and 2 mM glutamine were
      seeded into 96-well culture plates. After inoculation with 10(2) to 10(3)
      inclusion-forming units/ml of each strain of C. trachomatis, the culture medium
      was replaced by a maintenance medium containing 1 micrograms/ml of cycloheximide
      and serial two fold dilutions of the antibiotics. After 48 h incubation at 36
      degrees C in 5% CO2 atmosphere, cells were fixed and inclusion bodies were
      stained using fluorescein-conjugated anti-Chlamydia monoclonal antibodies. MICs
      were defined as the lowest antibiotic concentrations required to inhibit the
      development of a single inclusion. MICs 90% (mg/l) were 0.054 for doxycyclin,
      0.700 for ofloxacin and 0.150 for erythromycin. These results confirm the
      effective in vitro activity of the three antibiotics tested against C.
      trachomatis.

PMID- 8758474
TI  - [In vitro activity of a new quinolone, NM 394, against Chlamydia trachomatis].
AB  - A study of antimicrobial susceptibility of Chlamydia trachomatis was performed
      with a new quinolone, NM 394 (Laboratoire Dr. Bouchara). Ten C. trachomatis
      strains of four different genovars (3G, 4E, 2D, IDv) were grown in confluent
      McCoy cells on coverslips in multidishes (24 wells). For each C. trachomatis
      strain, two multidishes were prepared, one for MIC, one for MBC. Three inoculum
      titrated from 100 to 10000 IFU/ml were inoculated into wells. After incubation 48
      h at 37 degrees C, the cultures were fixed in methanol and examined for
      inclusions after staining with fluorescein-conjugated anti-Chlamydia antibody.
      The MIC was defined as the lowest antibiotic concentration at which no inclusion
      formation was observed. For the determination of MBC, the culture media was
      replaced with sucrose phosphate buffer (2SP) and the cultures were incubated
      without antibiotic for 48 h and stained. The MBC was the lowest antibiotic
      concentration at which no inclusion formation was observed after one passage
      without antibiotic. The increase of the inoculum from 10(3) to 10(5) IFU/ml did
      not affect significantly the activity of NM 394. All strains were inhibited by 16
      mg/l of NM 394. The IC 50 and 90 were 2 and 8 mg/l respectively. The MIC and the
      MBC values were similar.

PMID- 8758475
TI  - [Detection of pneumococci with reduced susceptibility to penicillin G using the
      ATB++STREP strip].
AB  - Antibiotic susceptibility of 104 clinical isolates of Streptococcus pneumoniae
      was routinely tested using ATB STREP strips (Bio-Merieux), and interpreted with
      ATB PLUS Expert V 2.3.1 software. In parallel, CMI of penicillin G was determined
      by Etest, strains with MIC < or = 0.06 mg/l were classified as penicillin
      susceptible. ATB system proved to be both sensitive and specific for the
      detection of strains of reduced susceptibility to penicillin G, accurately
      detecting 70 out of the 71 susceptible strains, and all of the 33 resistant
      strains. However the level of resistance cannot be deduced from ATB results.

PMID- 8758476
TI  - Use of the E-test for determining antimicrobial susceptibility of anaerobic
      bacteria.
AB  - Routine determination of antimicrobial susceptibility of anaerobic clinical
      isolates is difficult. The E-test is a practical alternative technique that we
      evaluated while testing clinical isolates in a multicenter study. The
      susceptibility to 9 antibiotics (penicillin, amoxycillin/clavulanate,
      ticarcillin/clavulanate, piperacillin/tazobactam, imipenem, cefoxitin,
      metronidazole, clindamycin, chloramphenicol) of 351 strains belonging to 63
      different species was determined by the NCCLS reference agar dilution procedure
      using Wilkins-Chalgren agar medium with 5% sheep blood and was compared to the E
      test performed on the same medium and using manufacturer's recommendations. The
      MIC values obtained with the E-test were generally one dilution lower than those
      obtained with the reference technique, 87.1% of the results being within two
      dilutions. In terms of susceptibility categories, 95.1% agreement was observed
      with 3.8% minor errors and only 0.5% major and 0.6% very major errors. With some
      Fusobacterium spp. and Clostridium spp. strains, the E-test was difficult to read
      or not interpretable because of the presence of growth within the inhibition zone
      of all beta-lactam antibiotics, representing a trailing phenomenon. We conclude
      that, if some interpretation difficulties are taken into account, the E-test is a
      convenient and reliable technique that can be applied in all clinical
      laboratories. It could be used for the individual testing of important anaerobes
      in certain clinical situations but cannot yet be considered as a reference
      technique. Its utility is emphasised by the increased resistance rate against
      clindamycin and the appearance of a few strains in the B. fragilis group with a
      reduced susceptibility against metronidazole.

PMID- 8758477
TI  - [Comparison of four methods for the determination of the susceptibility of 47
      strains of Pseudomonas aeruginosa to ceftazidime and cefepime: influence of the
      choice of interpretative criteria].
AB  - 47 isolates of Pseudomonas aeruginosa were tested for susceptibility to
      ceftazidime and cefepime by four methods (agar disc diffusion, E TEST and API
      ATB). Concordance between the methods is good, but the percentage of strains
      susceptible or of intermediate susceptibility depends of the interpretative
      criteria (French Committee for Antibiogram or National Committee Control for
      Laboratory Standards). An international agreement could be useful to compare the
      bacteriological and clinical studies.

PMID- 8758478
TI  - [Kinetics of bactericidal activity of cefepime and cefpirome alone or combined
      with gentamicin, amikacin or ciprofloxacin against Acinetobacter baumannii,
      Stenotrophomonas maltophilia and Enterobacter cloacae hyperproductive in
      cephalosporinase].
AB  - Nosocomial infections encountered in intensive care units are frequently due to
      Gram negative bacilli among which Stenotrophomonas maltophilia, Acinetobacter
      sp., and Enterobacter sp. The aim of the present study was to evaluate the in
      vitro bactericidal activity of the new broad spectrum cephalosporins cefepime
      (FEP) and cefpirome (CPO) alone or in combination with amikacin (AKN), gentamicin
      (GTN) or ciprofloxacin (CIP) against Acinetobacter baumannii, Stenotrophomonas
      maltophilia and Enterobacter cloacae producing a derepressed cephalosporinase.
      This study was performed by using the time-kill curve method on 24 h with a
      starting inoculum of 10(6) - 10(7) cfu/ml. The combination of FEP (4 mg/l) with
      AKN (4 mg/l) against A. baumanii only results in about 1 log decrease at 24 h,
      but when FEP is combined at 8 mg/l, the decrease reaches 4 log in 24 h. The
      combination of FEP (16 and 32 mg/l) clavulanic acid (4 mg/l) resulted in 3 log
      decrease at 24 h. When combined with CIP 2 mg/l, FEP (16 and 32 mg) resulted in 5
      and 6 log decrease in 24 h respectively. There were no survival bacteria at 6 h
      when FEP (32 mg/l) was combined with clavulanic acid (4 mg/l) and GTN (8 mg/l) at
      6 h. Used alone FEP (1 mg/l) or CPO (1 mg/l) against E. cloacae, a 3 log decrease
      occurs at 6 h followed by a regrowth at 24 h. Combined with AKN (2 mg/l), FEP (1
      mg/l) results in a 6 log decrease at 24 h, when CPO at 2 mg/l is needed for an
      equivalent result. These data show synergistic bactericidal activity of both new
      extended cephalosporins combined with AKN, GTN or CIP at concentrations
      achievable in biological fluid with adaptative dosage regimen.

PMID- 8758479
TI  - [Model of a miniature pig catheterized for pharmacokinetic and pharmacodynamic
      studies of anti-infective agents].
AB  - The miniature pig exhibits physiological and anatomical similarities to man. In
      addition, its reduced size and its docility make it appropriate for laboratory
      use. Curiously, this model remains seldom used in experimental pharmacokinetics.
      We present here in a chronic model of catheterized micropig allowing long term
      investigations of antiinfective agents. We work with Yucatan adult female
      micropigs weighing between 20 and 40kg. A catheter (60 cm x 2 mm) is placed in
      the external jugular vein under general anaesthesia and exits in the midline
      dorsal neck. The catheter is flushed every two days with heparinized saline to
      retain its potency. At the time of kinetic studies, the antiinfective agent is
      injected in an ear vein. Blood samples are obtained using the jugular catheter.
      The mean time of viability of the device is 13 weeks (SD: 10 weeks). Thrombosis
      was the main cause of arrest of the model. In conclusion, this chronic model of
      catheterized micropig is suitable for long term pharmacokinetic and
      pharmacodynamic investigations of antiinfective agents.

PMID- 8758480
TI  - [Pharmacokinetic interaction between itraconazole and rifampin in Yucatan
      miniature pigs].
AB  - The objective of this study was to examine the effects of rifampin on
      itraconazole pharmacokinetics, at steady state, in three Yucatan miniature pigs.
      The pits received daily during three weeks oral itraconazole at a dosage of 200
      mg at the beginning of the meal, then during the next two weeks oral itraconazole
      combined with an intravenous administration of rifampin at a dosage of 10
      mg/kg/day. The coadministration of rifampin resulted in a 18 fold decrease of the
      Cmax of itraconazole [from 113.0 (SD: 17.2) to 6.2 ng/ml (SD: 3.9)], and in a 22
      fold decrease of the AUC [from 1652.7 (SD: 297.7) to 75.6 ng.h/ml (SD: 30.01)].
      The active metabolite of itraconazole, hydroxyitraconazole, was undetectable.
      This study demonstrates that rifampin considerably affects itraconazole kinetics
      at steady-state in this model of micropig, probably by inducing the hepatic
      metabolism of itraconazole.

PMID- 8758481
TI  - [Amphotericin B into parenteral lipid emulsions. Galenic stability of mixtures.
      Preliminary results].
AB  - The amphotericin B in glucose solution is the reference's treatment of the major
      systemic mycoses. Because of its bad tolerance, certain authors put forward
      others vehicules such as fat emulsions. The aim of our work has been to study the
      physico-chemical stability of two regeneration's methods; P1: direct
      regeneration. P2: regeneration of 50mg of Fungizone in 5 ml of glucose serum and
      laced with 45 ml of Ivelip 20% versus PR: 50 mg of Fungizone in 50 ml of glucose
      serum. Our results seem to show that the P1 is totally incompatible with a
      parenteral administration, because 23% of the granulometric population has a
      diameter superior to 5 microns. The solution P2 seems better even if the pH is
      different from PR and a light depot comes after reconstitution.

PMID- 8758482
TI  - [Adequate intrathecal diffusion of teicoplanin after failure of vancomycin,
      administered in continuous infusion in three cases of shunt associated
      meningitis].
AB  - Glycopeptides which have excellent in vitro activity against the Gram-positive
      causal agents of meningitis unfortunately have a poor CSF penetration. Vancomycin
      distribution into CSF is improved when administered by a continuous intravenous
      route and staphylococcal shunt related infection have been reported to be cured.
      Teicoplanin has good in vitro activity against a lot of staphylococci, and
      activity superior to vancomycin, against streptococci and is less toxic. In three
      children with shunt ventriculitis (S epidermidis 2, S. faecalis 1) despite a
      continuous infusion, vancomycin 15 mg/kg over 60 minutes onset, then 50 mg/kg/day
      was clinically and bacteriologically ineffective with very poor CSF levels even
      if high blood levels. After failure of vancomycin we used teicoplanin as a
      continuous i.v. infusion 6 mg/kg over 60 mn onset, then 12 mg/kg/day. This
      treatment was quickly effective and well tolerated.

PMID- 8758483
TI  - TNF alpha production by whole blood from HIV-1 infected patients.
AB  - Production of cytokines by immunocompetent cells in vitro may be assessed after
      stimulation with polyclonal activators. Because it mimics the natural
      environment, diluted whole blood (WB) culture may be the most appropriate milieu
      in which to study cytokine production in vitro. We tested TNF alpha production by
      small volume of whole blood (25 microliters) from HIV-1 positive patients by
      using a one-step procedure that combines WB stimulation with LPS and PHA and
      cytokine measurement. We studied 30 patients without secondary infection or at
      distance of secondary infection staged according to the classification proposed
      by the CDC and 12 healthy seronegative subjects. The mean values of TNF alpha
      from patients were not statistically different from those from normal controls
      however in certain patients at different stages of the disease higher values than
      the mean +2 SD of controls and lower values than the mean -2 SD of controls were
      obtained. Heparinized blood from 5 control subjects had been collected
      sequentially during a period of 5 months. The individual variation of TNF alpha
      production were limited for all these individuals. For each of 6 HIV-1 patients,
      whole blood samples were collected sequentially during a period of 5 months and
      in most of patients large variations of levels of TNF alpha were observed from
      one sample to another one. Our method can detect abnormal cytokine production in
      HIV-1 positive individuals and can become a useful tool to investigate the role
      of cytokines in the outcome of HIV-1 infection.

PMID- 8758484
TI  - [In vivo and in vitro analysis of the ability of urinary catheter to microbial
      colonization].
AB  - Bacterial adhesion to biomaterials is a complex phenomenon involving numerous
      factors. The ability to reduce urinary catheters infections simply by general
      hygiene and asepsis is low: an ascending colonization cannot be avoided. This
      will lead to a clinical infection only if several factors favour the bacterial
      adhesion or the bacterial coaggregation and the feeding of the bacterial biofilm.
      Among the many factors involved in bacterial adhesion, we focused in this paper
      on the physical parameters of surface hydrophobicity of the urinary catheters
      (Van der Waals and acido-basic forces) and the surface hydrophobicity of the
      bacteria (BATH and zeta potential). We also compared scanning electron microscopy
      (SEM) of in vivo and in vitro infected urinary catheters. We provided evidence
      that the more hydrophobic the bacteria, the more they are able to colonize
      hydrophobic materials, whereas hydrophilic cells are able to colonize hydrophilic
      materials more easily. Some biomaterials were found to display an irregular
      texture of hydrophobic and hydrophilic areas: they favour both types of adhesion.
      Moreover the divalent cations (MgII) drastically increased the bacterial
      coaggregation and favour bacterial growth within the biofilm. Finally, an
      increase in urinary pH and ionic strength increases the colonization risk.
      Consequently, choice of urinary catheter biomaterials is essential as patient
      hygiene and diet in order to avoid clinical infections.

PMID- 8758485
TI  - CMV-IGG avidity and CMV-IGM concentration in both immunocompromised and
      immunocompetent patients.
AB  - Both CMV-specific IgG avidity index (AI) and CMV-specific IgM concentration were
      studied in different stages of CMV infection in both immunocompromised and
      immunocompetent patients. In these two groups (61 patients), a past CMV infection
      was associated with a mean AI constantly higher than 80%, just as the secondary
      infections observed in 18 immunocompromised patients (mean AI = 92%). In the 5
      immunocompromised patients with primary CMV infection, the maturation of CMV IgG
      activity was delayed for at least one year; in contrast, the CMV-specific IgM
      concentration was persistently high up to 12 months. In additions, the 10
      pediatric liver recipients who developed a primary CMV infection despite the
      administration of CMV specific immunoglobulins during the first two months post
      transplantation had initially a high AI for anti-CMV reflecting the AI of
      passively acquired immunoglobulins. In four immunocompetent patients whose sera
      were taken less than 100 days after seroconversion, the mean AI was low (less
      than 35%) and was associated for 3 out of these 4 patients with a high
      concentration of CMV-specific IgM (IgM ratio > 3). Likewise, the AI of CMV
      specific IgG in sera from 25 immunocompetent patients with suspected CMV
      infection was usually inversely correlated with CMV-specific IgM concentration.
      Thus, the use of these two parameters may help to date a CMV infection in
      immunocompetent patients especially in pregnant women.

PMID- 8758486
TI  - [Staphylococcus aureus resistant to methicillin. Survey of prevalence in Yvelines
      hospitals].
AB  - During 2 months (01.01.95-28.02.95), we noted for each Staphylococcus aureus (SA)
      isolates, identification and susceptibility methods, hospital size, medical
      speciality, source, penicillin (P) and methicillin (M) susceptibility. For each
      non repetitive methicillin resistant SA we noted phenotype of aminoglycoside
      resistance of SA to 6 antistaphylococci drugs. We isolated 399 SA, SAP sensitives
      6.5%, methicillin resistant SA (MRSA) 31.8%. MRSA in acute care unit 28.4%, non
      acute care unit 61.7%, surgery 28.6%, medicine 36.5%, orthopedics 34.5%,
      pediatrics 4%, ICU 38.8%, others 10.3%. MRSA from wound 28.2%, respiratory tract
      38.3% blood 22.5%, urine 58.5%, others 25.8% - MRSA kanamycin 1.7%, kanamycin
      tobramycin 36.2%, kanamycin, tobramycin, gentamicin 56.9% - MRSA erythromycin
      79.5%, pefloxacin 91.3%, rifampicin 53.5%, acide fusidique 8.7%, fosfomycine
      18.9%, TMP SMZ 5.5%. The proportion MRSA is equivalent among medical specialities
      predominant in urine cultures and respiratory tract. It should be better to carry
      on the survey for more than two months in each hospital.

PMID- 8758487
TI  - [Current aspects of the fecal flora of the newborn without antibiotherapy during
      the first 7 days of life: Enterobacteriaceae, enterococci, staphylococci].
AB  - Last years, il became obvious that the colonization pattern described in 1976
      1978 was no more valid: early colonization by Enterobacteriaceae at the 2-3 rd
      day of life in all newborns, with constant presence of antibioresistant
      strainseven in non treated newborns. To establish the new pattern of
      colonization, the same quantitative method of dilution and culture on selective
      media was used daily from day 1 to day 7 (5 days only for M). The number of
      Enterobacteriaceae, enterococci and staphylococci was determined in the stools of
      10 newborns in the Maternity unit (= M) (term 40 weeks +/- 1, birth weight 3,356
      g +/- 383), 10 in the Premature nursery (= P) (term 34.9 weeks +/- 1, birth
      weight 2,457 g +/- 676), and 14 in the Neonatal intensive care unit (= R) (term
      35.2 weeks +/- 3.8, birth weight 2,457 g +/- 763). The results establish that
      colonization by Enterobacteriaceae is no more constant at D3. It could be
      demonstrated only in 8/10 M, 1/10 P, and 6/14 R (statistically different - p <
      0.01 - between M and P). At D5, 9/10 M, 5/10 P, 10/14 R, and at D7, 6/10 P and
      10/14 R were colonized. Resistant Enterobacteriaceae (Escherichia coli,
      Klebsiella pneumoniae, Enterobacter cloacae) could be found in only 3/10 M, 4/10
      P and 6/14 R. Enterococci could be found in 1 newborn M, 2 P and 7 newborns R.
      Staphylococci appeared earlier: all newborns M, P and R were colonized at D2, 4
      and 5 respectively. These bacteria were coagulase negative, associated with
      Staphylococcus aureus in 3 P. Our hypothesis is that late colonization with
      Enterobacteriaceae and enterococci is due to the improvement of hygiene
      procedures and due to the decontaminating effect of antibiotics in other treated
      newborns (Enterobacteriaceae by 3 rd generation cephalosporin and enterococci by
      pharyngeal vancomycin).

PMID- 8758488
TI  - [Molecular epidemiology of pneumococci with decreased susceptibility to
      penicillin isolated in a Parisian pediatric hospital].
AB  - Pneumococci with decreased susceptibility or resistant to penicillin (PRP) have
      been isolated with an increasing frequency in France. Among PRP, isolates of
      serotypes 23F and 9V were the most frequently recovered in our children's
      hospital. Penicillin-resistance is due to the appearance of altered penicillin
      binding proteins (PBPs) with reduced affinity for beta-lactam antibiotics. 3 PBPs
      have been well studied, 2b, 2x and 1a, and the sequences of their genes have been
      determined. Our molecular epidemiological study of 14 PRP 9V and 26 PRP 23F
      isolated mainly from otitis in 1993-94, consisted of determining chromosomic
      restriction patterns (Apa I) by pulsed-field gel electrophoresis, and restriction
      patterns (Hinf I) of PBP genes pbp 2b, pbp 2x and pbp 1a after PCR. All the PRP
      9V exhibited the same pulsotype and identical patterns for each of the genes pbp
      2b, pbp 2x and pbp 1a, suggesting a clonal origin. The origins of PRP 23F were
      more heterogenous: 5 clones could be defined, with one predominant clone composed
      of 20 isolates. Most of the PRP 23F shared identical profiles for the genes pbp
      2b, pbp 2x and pbp 1a with the PRP 9V, suggesting a horizontal transfer of DNA.
      Molecular markers, which provide more informations than serotyping, were useful
      to clarify the complex epidemiology of PRP.

PMID- 8758489
TI  - Pulsed field gel electrophoresis in Streptococcus pneumoniae isolated in France
      and Portugal.
AB  - During a multicenter surveillance study on Streptococcus pneumoniae resistant to
      antibiotics in Portugal we have analyzed, within the predominant serotypes of
      penicillin G resistant strains, the chromosomal DNA restriction profiles by
      pulsed field gel electrophoresis. The aim of this work was to compare the PFGE
      restriction profiles of penicillin resistant pneumococci isolated in France with
      those of Portuguese strains within each serotype. We have studied fifteen
      penicillin resistant strains isolated in different geographical regions of
      France, and representing equally the three predominant resistant serotypes 23F,
      9V and 14. In general we observed an important homogeneity of profiles within
      each serotype, in the two countries. In serotype 23F, the five French strains
      studied show subtypes of a pattern called A, also detected in the majority of 23F
      Portuguese strains; similarly 4 of the 5 serotype 9V strains belong to subtypes
      of the pattern G, also common within 9V Portuguese strains; 4 of the 5 strains of
      serotype 14 show a subtype of profile H, found often in Portuguese strains. The
      observed homogeneity of chromosomal DNA restriction profiles within each serotype
      in the two countries, confirms the importance of geographic spread of
      pneumococcal resistant clones, previously described.

PMID- 8758490
TI  - [Molecular typing by pulsed field gel electrophoresis of Stenotrophomonas
      maltophilia isolated in a department of hematology].
AB  - Stenotrophomonas maltophilia is an important nosocomial pathogen. The increased
      isolates of S. maltophilia among hematology unit patients led to an
      epidemiological survey. Over 26 months, 24 strains isolated from 23 patients and
      an environmental isolate from blood pressure armband have been identified. The
      isolated were first analysed by the use of phenotypical markers: biotype,
      antibiotic susceptibility, but the minor differences observed justified a
      genotypic analysis. Pulsed field gel electrophoresis of genomic DNA was carried
      with XbaI and DraI restriction endonucleases by contour-clamped homogeneous
      electric field method (CHEF). The data obtained showed a great genomic diversity
      within the species S. maltophilia. Nevertheless, the same restriction profile was
      found for 3 patients and 3 other profiles were obtained for 3 couples of patients
      hospitalized at the same time. All the other strains isolated from subjects
      hospitalized during the same period exhibited pulsotypes independent from each
      other. Compared to biotypes and antibiotic susceptibility, these results indicate
      field only with non modified primers, and the absence of 460 mutations was
      confirmed by sequencing. Two isolates P1 and P2, from a transplanted patient were
      amplified with both primers MCMM and MCMW: sequencing analysis shown the presence
      of a mixture of strains, one of them harbouring A- > G 1378 mutation. One
      resistant strain was amplified neither with MCMM nor with MCMW: a C- > T silent
      mutation at nt 1368 was present. As sequencing analysis confirmed PCR results,
      discriminative PCR enables isolates to be rapidly assessed for the presence or
      absence of 460 mutations. Moreover, it can distinguish Met to Val from Met to Ile
      mutations, and allows the analysis of mixtures of sensitive and resistant
      strains.

PMID- 8758491
TI  - Pseudomonas (Burkholderia) cepacia in children with cystic fibrosis:
      epidemiological investigation by analysis or restriction fragment length
      polymorphism.
AB  - Since 1987, Pseudomonas cepacia has been isolated with an increasing frequency in
      the expectorants of children with cystic fibrosis followed at the Hopital
      d'enfants Armand Trousseau (Paris, France). Colonization by P. cepacia may be
      responsible for serious secondary infections and rapid deterioration in
      respiratory function in these patients. Among the 130 children attending our
      centre, 14 (8 girls and 6 boys) aged 3 to 18, exhibited chronic colonization. 132
      isolates, originating from sputum obtained between 1992 and 1994 were studied.
      Nine biochemical patterns and 6 antibiotic susceptibility patterns at least were
      defined, therefore exhibiting great polymorphism. Chromosome restriction patterns
      with Xba I after pulsed field gel electrophoresis enabled 4 pulsotypes to be
      identified: A, B, C and D. Thirteen patients harboured pulsotypes A, C and D, and
      1 patient pulsotype B, the last being quite distinct from the first three.
      Pulsotypes A, C and D were almost similar, suggesting that closely related
      strains, probably the same strain, was harboured by 13 of the 14 patients. The
      origin could be contamination from a single source, or stem from patient-to
      patient crossed transmission.

PMID- 8758492
TI  - [Mycological monitoring of Candida albicans infections in various hospital care
      units. Molecular typing of isolated strains and epidemiological survey].
AB  - To evaluate risk factors associated with the nosocomial infection of Candida
      albicans, a prospective study is conducted twice for three months in three
      intensive care units. Samples from patients HIV negatives, non neutropenic and
      non immunodepressive are collected as they came in the unit, on several anatomic
      sites. Every C. albicans carriers are included in a mycological monitoring.
      Samples from environmental surfaces, hands and deep pharynx from hospital
      personnel were also cultured. Strains genetic profile are defined by isoenzyme
      electrophoresis technique. Thirteen polymorphic loci allowed samples classement
      into 52 electrophoretic types (ET). If only one crossed contamination is
      described, strains regroupment into some ET incites us to extend this study. C.
      albicans strains from patients closed environment have never been isolated.

PMID- 8758493
TI  - [Analysis of restriction fragment length polymorphism (RFLP) of Mycobacterium
      tuberculosis strains isolated from patients with several episodes of
      tuberculosis].
AB  - Analysis of restriction fragment length polymorphism (RFLP), using a DNA probe
      directed against the insertion sequence IS6110, was applied to strains of
      Mycobacterium tuberculosis successively isolated from four patients. In order to
      determine the cause of recurrence in these patients, the RFLP patterns of the
      corresponding isolated were analyzed. The profils obtained from the strains
      isolated from each of the patients were identical, thus suggesting that a
      relapse, rather than an exogenous reinfection with a new strain, was the cause of
      recurrence. The RFLP patterns of successive isolated remained unchanged during
      periods of time ranging from 5 months to 7 years, and were not modified after
      development of rifampin resistance. These results demonstrate the stability of
      the polymorphism detected by the IS6110 probe. Therefore, RFLP analysis is a
      powerfull epidemiologic tool to distinguish relapse from exogenous reinfection.

PMID- 8758494
TI  - [Resistance of cytomegalovirus to ganciclovir: rapid detection of the mutations
      460 of the UL97 phosphotransferase].
AB  - The substitution of methionine by either isoleucine or valine at residue 460 in
      the UL97 phosphotransferase has been shown to be responsible for resistance to
      ganciclovir (GCV) in 30% of resistant cytomegalovirus (CMV) isolates [4]. These
      substitutions require one nucleotide change in the gene (G- > T 1 380 and A- > G
      1378 respectively). The aim of this study was to develop a discriminative PCR
      assay for rapid detection of these DNA changes. A PCR assay was duplicated in
      parallel for each mutation; to detect G- > T 1380 each reaction mixture contained
      primer VSUL14 and either primer LNW to distinguish wild type residues or LNM to
      distinguish mutant residues, and for A- > G 1378 primers were VSUL8 and either
      MCMW to detect wild type sequences or MCMM to detect mutated residues. For
      optimal discrimination, primers MCMW and MCMM were designed with a mismatch at
      position 3'-1. The reference strains AD169, Davis and Towne, a laboratory GCV
      resistant mutant RCL1.7, and 33 CMV isolates (10 resistant, 2 indetermined and 21
      sensitive) were tested by PCR. AD169, Davis and Towne, and 30 isolates were
      amplified only with non modified primers, and the absence of 460 mutations was
      confirmed by sequencing. Two isolates P1 and P2, from a transplanted patient were
      amplified with both MCMM and MCMW: sequencing analysis shown the presence of a
      mixture of strain, one of them harbouring A- > G 1378 mutation. One resistant
      strain was amplified neither with MCMM nor with MCMW: a C- > T silent mutation at
      nt 1368 was present. As sequencing analysis confirmed PCR results, discriminative
      PCR enables isolates to be rapidly assessed for the presence or absence of 460
      mutations. Moreover, it can distinguish Met to Val from Met to Ile mutations, and
      allows the analysis of mixtures of sensitive ad resistant strains.

PMID- 8758495
TI  - [Polyvalent hyperimmune immunoglobulins prevent the infection of monocytic type
      cells by human cytomegalovirus].
AB  - Monocyte/macrophage cell types can be infected with Human Cytomegalovirus (HCMV)
      could be a reservoir and a vehicle for virus spread in infected patients. We
      developed a model to study the effects of antiviral molecules on these cells. The
      monocytic-like cell line THP-1 and the human diploid cells MRC-5 were used. THP-1
      cells were cultivated with a phorbol 12-myristate 13-acetate (PMA) for 24h prior
      to the infection. We studied infection of these cells with reference strain (AD
      169). A cell free virus suspension of HCMV was preincubated with hyperimmune
      polyvalent immunoglobulins. The infection of the cells was studied on the basis
      of immune detection of viral immediate early antigens (IEA) in nucleus 24h after
      culture. Our results showed that hyperimmune polyvalent immunoglobulins have been
      able to neutralize fibroblasts and THP-1 cells infection, whereas control
      antibodies did not inhibit the infection of the cells. This is the first report
      of the use of monocytic-like cells for testing the efficiency of anti-CMV
      molecules.

PMID- 8758496
TI  - Identification of HCV genotypes in the Calabria region.
AB  - The present work describes the distribution of HCV genotypes in Calabria. The
      data presented suggest that, in the sample of population investigated, genotype
      1b is the most prevalent followed by the 2b and the 2a.. In addition it is
      important to note that in Calabria the prevalence of genotype 1b is strikingly
      high in respect to the other Italian pullulation. An Association between HCV type
      1b and the more severe clinical course of the liver disease has been reported.
      Although the data presented indicate that in Calabria most of the subjects
      enrolled in the study are infected by a virulent HCV strain, no association has
      been found with more severe clinical manifestations.

PMID- 8758497
TI  - [Predictive value of a rapid negativity of serum virus C viremia during treatment
      with interferon alpha in patients with chronic hepatitis C].
AB  - Interferon alpha (INF) used for chronic hepatitis C treatment induces a response
      in less than 25% of patients. The aim of this study was to appreciate the
      predictive value of the delay of clearance of hepatitis C virus (HCV) viremia
      after onset therapy and to compare it with other virological markers such as
      viral load before treatment and viral type. Thirty one patients with chronic
      hepatitis C, treated with 3 MU Interferon, 3 times a week for 6 months, were
      followed until 6 months post-treatment. Response was defined according to the
      normalisation of transaminases levels and loss of HCV viremia. Five patients were
      long term responder, eleven patients were complete to relapse responder and
      fifteen patients were non responder. Serum HCV RNA level, HCV type and serial
      detection of serum HCV RNA were determined and correlated with the long term
      response to INF. Patients with long term response had lower pre-INF viral load
      compared to the complete to relapse responder or to the non responder (p <
      0.001). A rapid clearance of serum HCV RNA (1 month) is observed for all the long
      term responder (p < 0.001). The lowest viral load is also observed in these
      patients (p < 0 05). By contrast, although the number of patient is low, we were
      not able to observe a relation between the viral type and the response to
      treatment. In conclusion this data indicate that the delay of clearance of HCV
      RNA is also a good predictor of response to INF therapy. Furthermore a rapid
      clearance of HCV RNA in patients with a very weak pre-INF viral load is strongly
      associated with long term response (positive predictive value: 100%).

PMID- 8758498
TI  - [Hepatoportal sclerosis, nodular regenerative hyperplasia, incomplete septal
      cirrhosis: lesions of hepatic microcirculation?].

PMID- 8758499
TI  - [Treatment of common bile duct lithiasis under laparoscopy. A prospective
      multicenter study in 189 patients].
AB  - OBJECTIVES: The aim of this study was to assess the feasibility and results of
      common bile duct laparoscopic treatment and exploration in patients with
      choledocholithiasis. PATIENTS AND METHODS: From November 1991 to December 1994,
      189 consecutive malades (120 females; mean age 68 years, range: 21-92) with
      choledocholithiasis identified during routine intraoperative cholangiogram
      underwent surgical exploration of common bile duct in 5 surgical centers. Twenty
      patients were referred to surgery after unsuccessful endoscopic sphincterotomy.
      RESULTS: Following laparoscopic exploration and intraoperative cholangiography,
      common bile duct stone extraction by laparoscopy was not attempted in 11 patients
      (5.8%). The common bile duct was successfully cleared of all stones in 153
      patients (81% of the overall population and 86% of laparoscopic attempts), either
      via the transcystic route (n = 97) or through choledocotomy (n = 56). Eighteen
      patients required conversion to open surgery, 16 for unsuccessful stone
      extraction and 2 despite successful stone extraction. Postoperative endoscopic
      sphincterotomy was required in 7 patients (4.4%) for retained stones after
      laparoscopic treatment. There were no postoperative deaths (95% confidence
      interval 0-1.6%), and follow-up, ranging from 3 to 42 months, has shown no
      further clinical evidence of retained stones. CONCLUSION: Diagnosis and treatment
      of common bile duct stones is feasible by laparoscopy, and the results in this
      series compare favorably with those of conventional surgical treatment. Complete
      treatment of biliary lithiasis, in one operation, avoids the pitfalls of patient
      selection for preoperative endoscopic retrograde cholangiography and the risks of
      endoscopic sphincterotomy.

PMID- 8758500
TI  - [Extrahepatic manifestations of hepatitis A virus infection].

PMID- 8758501
TI  - [Frontiers of digestive surgery using laparoscopy].

PMID- 8758502
TI  - [Role of celioscopy in acute obstructions of the small intestine].
AB  - OBJECTIVES: The aim of this study was to evaluate the possibilities of
      laparoscopy in the diagnosis and treatment of acute small bowel obstruction.
      METHODS: Thirty five patients, with less than three abdominal incisions, who had
      undergone initial laparoscopy for acute small bowel obstruction, were reviewed.
      The small bowel was mobilized to determine the cause and site of obstruction.
      RESULTS: In 31 cases, small bowel obstruction was caused by a single or numerous
      obstructing bands. Among 31 cases of adhesions, laparoscopic treatment of
      intestinal obstruction was possible in 16 cases (51.6%). In 15 cases, laparoscopy
      had to be completed by laparotomy: numerous adhesions could not be divided in 12
      cases; intestinal ischemia which required resection was present in 3 cases. There
      was no hospital mortality and postoperative complications occurred in 19% of
      cases. Multivariate analysis demonstrated a relation between need to complete
      laparoscopy by laparotomy and two factors : presence of signs of peritoneal
      irritation (P < 0.05) and intestinal obstruction caused by numerous adhesions or
      bands (P < 0.05). Mean hospital stay and postoperative ileus were significantly
      shorter in the "laparoscopy" group than in the "laparoscopy + laparotomy" group.
      CONCLUSIONS: Laparoscopic treatment of acute small bowel obstruction is difficult
      and was possible in only half of the cases. The first port should be inserted by
      open technique to avoid the risk of perforation of distented small bowel. When
      laparoscopy shows numerous adhesions, laparoscopic treatment should not be
      pursued, and laparotomy should be recommended to avoid the risk of visceral
      perforation.

PMID- 8758503
TI  - [Laxative effect and tolerance of lactulose administrated in one or two intakes
      in the treatment of chronic idiopathic constipation. Groupe d'Investigateurs
      O'Ile-de-France (GIIF)].
AB  - OBJECTIVES: The aim of this study was to compare the tolerance and effects of
      lactulose taken at a daily dose of 20 mg in one or two intakes, in the treatment
      of idiopathic chronic constipation. METHODS: A total of 121 outpatients (30 men,
      91 women, mean age 55) was included in a prospective double blind crossover
      multicentric study. Patients took lactulose according to two different ways of
      administration and for two successive 3-week periods. Each period consisted in 2
      weeks of adaptation and one week of evaluation. At the end of each period, a
      global visual satisfactory scale was evaluated as a global index. Patients
      collected every day the frequency and the aspects of the stools, the quality of
      exoneration and the existence of digestive symptoms. RESULTS: Number of stools
      per week (7.29 +/- 3.20 vs 7.08 +/- 3.03), consistency, quality of exoneration,
      were equivalent whatever the number of intakes and the period of treatment. With
      one or two intakes, the satisfactory index was the same but significantly better
      at the end of the second period. With one or two intakes, frequency and intensity
      of side effects were low and identical. They mostly occurred during the first
      period. CONCLUSION: Effects and tolerance with one single intake of lactulose (20
      g) in the evening and with two intakes, were found to be equivalent. Effect on
      exoneration persists during the six weeks of administration and then tolerance
      improves.

PMID- 8758504
TI  - [Helicobacter pylori and gastroduodenal lesions in 547 symptomatic young adults].
AB  - OBJECTIVES: Helicobacter pylori (H. pylori) is involved in the pathogenesis of
      gastric inflammatory disorders. Both antral chronic gastritis and H. pylori
      infection prevalence increase with age. The aim of the study was to assess the
      prevalence of H. pylori infection in young adults and to study the relationship
      between endoscopical and histological features and H. pylori infection. METHODS:
      The study concerned 547 young patients (age: 18-25 years), undergoing endoscopy
      for upper gastrointestinal symptoms. The severity and the activity of chronic
      gastritis was graded by histological examination of antral biopsies. The
      diagnosis of H. pylori infection was based on histology and culture or urease
      test. RESULTS: Fifty-three percent of the patients had a normal endoscopy; 44
      ulcers were found: 34 duodenal ulcers and 10 gastric ulcers. H. pylori infection
      was detected in 34% of cases. The prevalence of H. pylori infection was 29.8% in
      non-ulcer patients, 50% in gastric ulcers and 91% in duodenal ulcers (P < 0.01).
      Duodenal ulcer, aspect of antral mosaic mucosa and nodular gastritis, were
      closely related to the presence of H. pylori. There was a significant
      relationship between H. pylori infection and both the severity (P < 0.01) and the
      activity (P < 0.01) of the antral chronic gastritis. The prevalence of follicular
      gastritis was 22% : it was present in 60% of H. pylori positive patients and 2.4%
      of H. pylori negative patients. H. pylori infection was more frequent in patients
      from Africa than in Europeans (P < 0.01). There was no significant association
      between H. pylori infection and different types of diets, settlements (rural vs
      urban) or symptoms. CONCLUSION: These results show that in the young population
      studied, duodenal ulcer, nodular gastritis, antral mosaic mucosa, active chronic
      gastric and follicular gastritis are closely related to H. pylori infection. They
      suggest that in the subgroup of non ulcer symptomatic patients, H. pylori
      prevalence is higher than in the general population.

PMID- 8758505
TI  - [Is celioscopic surgery for colorectal cancer currently justified?].

PMID- 8758506
TI  - [Choledochoduodenal fistula: an unusual complication of duodenal ulcer].
AB  - We report a case of choledochoduodenal fistula in a patient with a duodenal ulcer
      and poor compliance to treatment. The fistula tract was demonstrated on a plain
      abdominal X-ray (presence of air in the biliary tract), and was confirmed by a
      fistulography from the site of the ulcer (opacification of the bile duct). A
      Finsterer type 2/3 gastrectomy was performed in this patient, leading to the
      treatment of the ulcer and disappearance of the fistula following a gastrojejunal
      shunt of the duodenum. Clinical outcome was excellent.

PMID- 8758507
TI  - [Specific respiratory manifestations associated with hemorrhagic rectocolitis.
      Analysis of a case and review of the literature].
AB  - Respiratory impairments occurring as systemic manifestations of ulcerative
      colitis are often misinterpreted. We report a case of chronic productive
      bronchitis associated with ulcerative colitis; symptoms appeared after colectomy.
      Clinical features distinguished it from common chronic bronchitis: it occurred in
      a woman without respiratory disease or smoking history, a chronic productive
      cough without bronchiectasis, negative infectious investigations, severe
      endoscopic and histologic lesions, and above all remarkable steroid efficacy.
      Systematic research and early treatment of these manifestations avoids
      aggravating pulmonary disease, especially secondary bronchiectasis. Though less
      frequent, other respiratory manifestations of ulcerative colitis have been
      described, such as asphyxiating tracheal stenosis, pneumonia or interstitial
      pulmonary diseases, pleurisy or pleuro-pericarditis.

PMID- 8758508
TI  - [Acute myelitis after immunization against hepatitis B with recombinant vaccine].

PMID- 8758509
TI  - [Acute hepatitis related to the ingestion of terbinafine].

PMID- 8758510
TI  - [Severe hepatic lesion after a long distance running].

PMID- 8758511
TI  - [Serum smooth muscle antibodies with anti-actin specificity appeared during
      treatment with interferon alpha].

PMID- 8758512
TI  - [Control of the course of acute mesenteric ischemias: value of celioscopy].

PMID- 8758513
TI  - [Hemorrhagic esophageal papilloma associated with the ingestion of non-steroidal
      anti-inflammatory agents].

PMID- 8758514
TI  - [Severe myalgias: an unusual undesirable effect of levamisole combined with 5
      fluorouracil].

PMID- 8758515
TI  - [Rectal localization of Wegener's disease].

PMID- 8758516
TI  - [Development of an in vitro cellular model of Crigler-Najjar disease: towards a
      gene therapy of the disease].

PMID- 8758517
TI  - [Prevention of the risk of contamination in the operating room. Must a
      preoperative serologic HIV test be performed in each patients?].

PMID- 8758518
TI  - [Role of functional explorations in the surgical practice in patients consulting
      for defecation disorders].

PMID- 8758519
TI  - [Concomitant preoperative radiochemotherapy for rectal cancers].
AB  - In December 1994, The French Consensus Conference on the Treatment of Rectal
      Cancer stated that: "Preoperative irradiation improves local control in T3 and T4
      resectable rectal cancer patients and is recommended". Recent data indicate that
      this approach not only reduces local failure but also increases overall survival.
      The therapeutic ratio depends on the total dose delivered and technical
      parameters. Inadequate radiotherapy techniques leeds to increased toxicity and
      masks the potential benefits of the treatment. Combined preoperative chemo
      radiotherapy, a promising issue in rectal cancer patients, is now under
      evaluation in a large European phase III trial (EORTC 22921).

PMID- 8758520
TI  - [Radiation injuries of the small intestine. Surgical treatment].
AB  - From 1978 to 1992, 55 patients (48 women: 87%) with a mean age of 62 years (35
      89) underwent 70 operations for radiation injury of the small bowel. Primary
      pathology treated with radiotherapy was gynecologic cancer (40: 72%), digestive
      malignancy (9: 16%), male genital cancer (4: 7%), carcinoma of the bladder (2:
      3%). External radiation was performed alone (47: 85.5%) or associated with
      intracavitary radium or cesium (8: 14.5%), mean radiation dose was 50 Gy for 35
      patients and not specified for 20 but greater than 45 Gy for all patients.
      Fifteen patients had associated chemotherapy. Latent period between radiation
      injury and first symptoms was 39 months (1-16 years) and 72 months (3-26 years)
      between radiation and surgical treatment. There were 28 solitary lesions (mean
      length: 148.5 cm) with 5 associated colonic injuries, 27 multiple lesions of the
      small bowel (mean length: 187.5 cm) with 21 associated colonic injuries. Twenty
      one lesions of the abdominal wall and 13 lesions of the urinary tract were also
      associated. Nineteen patients had pre-operative total parenteral nutritional
      assistance. Surgical treatment was performed for chronic obstruction in 46
      patients, for fistulae in 5 or for an acute complication in 4 (perforating
      peritonitis: 3, occlusion: 1). Operations performed were: small bowel resection
      (32), associated with bypass (2); internal by-pass (15); dissection of adhesions
      and/or stomy (7). RESULTS: Operative mortality was 2 (6.2%). Morbidity occurred
      in 16 (29%) with 3 anastomotic fistulae. Functional results were good for 36
      patients (24 resections, 7 by-pass), poor for 2 (1 resection). Failure leading to
      a second operation occurred in 15 (5 resections, 8 by-pass). COMMENTS: 1) pre
      operative nutritional assistance improves operative results; 2) intestinal
      resection is preferable to internal by-pass whenever it can be performed without
      extreme risk or unacceptable sequelae.

PMID- 8758521
TI  - [Results of surgical treatment of complicated paraesophageal hernias].
AB  - From January 1979 to May 1995, 18 patients (4 men, 14 women) with a mean age of
      75.4 +/- 12.5 yr underwent surgery for a complicated paraesophageal hiatus
      hernia. In 5 patients, the complication was the first sign of the diagnosis.
      Thirteen patients had a history of digestive, respiratory, or cardiac symptoms
      (mean duration of symptoms 74 mo.; range 2-240 mo.); 9 of them were aware that
      they had a hiatus hernia. Ten patients presented with acute obstruction
      (associated with a perforation in 1 case, jaundice in 1 case, and righy lower
      lobe pneumonia in 1 case). Hemorrhage occurred in 6 patients (hematemesis 4
      cases, melena 2 cases). One patient had a perforation and another had an abscess
      of the lower right lobe. Surgery was performed via a transabdominal approach in
      all cases (5 times as an emergency, 12 times as a delayed emergency procedure,
      and once as an elective procedure). The procedure was delayed in 13 cases because
      of successful nasogastric decompression. All patients underwent reintegration of
      the stomach, diaphragmatic repair and gastropexy. An antireflux procedure was
      performed in 14 cases. Seven patients had an ancillary procedure (including one
      splenectomy following decapsulation). There were no postoperative deaths. Two
      patients who underwent emergency surgery developed a benign complication. The
      outcome of 17 patients is known; none of them developed a recurrence. One patient
      who did not undergo an antireflux procedure presented with gastroesophageal
      reflux; another experienced pain during eructation. In conclusion, nearly two
      thirds of all patients who present with an acute complication can benefit from
      medical preparation before surgery, a strategy that improves results.

PMID- 8758522
TI  - [Morbidity of lateral loop ileostomy].
AB  - The aim of this retrospective study was to assess the morbidity of twisted loop
      ileostomy (TLI). Between 1985 and 1994, 83 TLI were performed in 79 patients.
      Before TLI closure, 13 patients (16%) presented complications, requiring surgery
      in 5 cases. Small bowel obstruction (7 cases: 8%) and high stoma output (4 cases:
      5%) were the commonest complications. After stoma closure (performed in 76
      cases), 8 patients (10.5%) presented complications, requiring surgery in 3 cases.
      The most commonest complication was enteric fistula (4 cases: 5.3%) requiring
      reoperation in 2 cases. This procedure adds a separate set of postoperative
      complications, which tend to be minor in nature without any permanent sequelae
      and which can be minimized by a meticulous surgical technique. This technique
      remains a safe and effective procedure for fecal diversion.

PMID- 8758523
TI  - [A radical treatment of villous tumors of the duodenum].
AB  - Three cases of large villous tumors of the second part of the duodenum treated by
      pancreaticoduodenectomy are reported. These lesions are in frequent and
      premalignant. Their treatment can be either local, endoscopic or surgical, or
      radical. The malignancy of the tumors is often missed preoperatively. The
      frequent recurrence after local excision and the theoretical risk of lymph node
      invasion even for carcinoma in situ compared with the low operative risk of
      whipple's procedure in the authors' experience lead them to propose radical
      treatment for extensive villous tumors of the second part of the duodenum.

PMID- 8758524
TI  - [Primary adenocarcinoma of the duodenum. Study of three cases and review of the
      literature].
AB  - The authors report three cases of primary adenocarcinoma, two concerning the
      duodenum and the third concerning the duodenojejunal junction. These rare tumours
      are characterized by polymorphic and non specific clinical signs. Diagnosis is
      suspected by upper gastrointestinal fibroscopy and barium swallow, and confirmed
      by biopsies. Prognosis varies according to histological differentiation and lymph
      node extension. Whipples operation is the sole curative procedure in the absence
      of local lymph node involvement. Cases of extensive invasion are managed by bilio
      digestive by-pass.

PMID- 8758525
TI  - [Amebic abscess of the liver: ultrasound guided puncture].
AB  - The aim of this study is to present the results of ultrasound-guided needle
      aspiration in amoebic abscess of the liver in 1289 patients. Out of 1512 patients
      hospitalized from 1990 to 1995 for an amoebic abscess of the liver, 1289 (83.6%)
      were treated by this approach. The abscesses of less than 40 mm (8.9%) were
      treated medically, and those of more than 170 mm (0.6%) were operated on. The
      abscesses with peritonitis (5.2%) were also operated on. A treatment with
      metronidazole or dehydroemetin was associated with the surgical treatment or with
      the aspiration of the abscess. There was no death. A second aspiration was
      necessary in 24.9% of the patients, and a third one in 9.4%. Three complications
      were observed, two hemorrhages and one fistula. Nine patients had a recurrent
      abscess after their discharge from hospital. Four failures were observed in
      patients with abscesses of more than 170 mm in diameter. Results were considered
      as good in 1273 patients (98.7%). These results suggest that in amoebic abscess
      of the liver with a diameter between 40 and 170 mm, aspiration associated with
      amoebic treatment may be the standard treatment. Smaller abscesses usually
      recover with medical treatment alone, and greater abscesses need surgical
      drainage.

PMID- 8758526
TI  - [Computers in a private surgeon's office. "Do it yourself" or "one is never
      served better than by oneself"].
AB  - In an attempt to minimise the administrative work involved in private surgical
      practice, the author naturally considered the use of computers. After studying
      the medical software market, he was convinced that most software was better
      adapted to general practice than to surgery. He concluded that the best person to
      design a surgical software would be the surgeon himself, provided he was prepared
      to spend some of his leisure time to develop a computer application. The software
      developed is a large integrated application facilitating all of the functions
      necessary to good functioning of the surgical office. It therefore ensures filing
      of medical records, correspondence, accounts, management of salaries, and
      appointments, as all of these sectors are related to the surgical activity
      itself. This approach led to the design of an application, and its functioning
      and the possibilities provided are described.

PMID- 8758527
TI  - [Perforations and porosity of surgical gloves. Frequency, mechanism, risk].
AB  - Surgical gloves constitute part of the most exposed barrier material, as one half
      of accidental exposures to blood in the exposures to blood in the operating room
      involve the hands. Approximately 15% of gloves tested at the end of the operation
      were found to be perforated. Double gloving lowers this rate to 5% with
      apparently acceptable tolerance for surgeons. Although surgical glove are
      initially impermeable to various viruses, the porosity increases with the
      duration of use. This porosity is related to hydratation and deformation of latex
      fibres. The maintenance of a good barrier function of surgical gloves requires
      regular changing, at least hourly, in the current state of knowledge.

PMID- 8758528
TI  - [Anorectal melanoma. Apropos of a distant recurrence].

PMID- 8758529
TI  - [Renal tolerability of cisplatin].

PMID- 8758530
TI  - [Role of biopsy of the accessory salivary glands in Lofgren's syndrome and other
      forms of sarcoidosis].
AB  - The diagnosis of sarcoidosis requires histopathological analysis. Easy accessible
      site of biopsy is seldom. A systematic labial salivary gland biopsy was performed
      in 62 suspected sarcoidosis: 22 patients with Lofgren syndrome (group I), and 40
      patients with systemic sarcoidosis (group II). Systematic bronchial biopsy was
      performed in eight patients of group I and ten patients of group II. If
      systematic biopsies were negative, direct biopsies were performed (lymph node,
      skin, kidney, liver). In group I, 8/22 labial salivary gland biopsies and 1/8
      bronchial biopsies were positive; in group II, 17/40 labial salivary gland
      biopsies and 5/10 bronchial biopsies were positive. In the other patients, direct
      biopsies were positive: 27 lymph nodes, eight skin, eight hepatic, four kidney
      biopsies. In conclusion, labial salivary gland biopsy (even in the absence of
      sicca syndrome) is more reliable than systematic bronchial biopsies, particularly
      in Lofgren syndrome and may avoid in 30 to 50% of the cases more aggressive and
      dangerous biopsies such as liver, kidney or deep lymph nodes biopsies.

PMID- 8758531
TI  - [Iatrogenic drug-induced diseases, requiring hospitalization, in patients over 65
      years of age. 1-year retrospective study in an internal medicine department].
AB  - Iatrogenic pathology is mainly seen in the elderly. In a one year retrospective
      study, we showed that drug toxicity was responsible for 87 cases requiring
      hospitalisation in patients aged 65 years and above (7.7% of hospital admission
      for patients over 65 years). The major manifestations were: 21 cases of sera
      electrolyte disturbance, 19 concerning gastro-intestinal tract and liver, 16
      cardiological disorders, 13 neurological complications, ten involving the
      endocrine system, six hematological complications. The most common drugs involved
      were: antihypertensive agents (36%), of which 20.5% were diuretics,
      psychotherapeutic drugs (24.8%), anti-inflammatory drugs (17.8%). The average
      cost per patient was calculated to 20,602 FF per patient. Impossibility for
      direct return to the original dwelling place was another complication in 29% of
      hospitalisations related to iatrogenic disorders. The high number of drugs taken
      daily increases the risk of drug interactions which was responsible for
      iatrogenic accidents in 12.6% of the patients of this study.

PMID- 8758532
TI  - [Food-dependent Cushing syndrome: a new entity of organic hypercorticism].
AB  - Diagnosis of Cushing's syndrome is quite difficult in endocrinology. Spontaneous
      Cushing's syndrome is usually divided into two subgroups, one which is dependent
      on corticotropin (ACTH) and another one which is not. In the first class are
      Cushing's disease, the ectopic corticotropin syndrome and the rare ectopic
      corticotropin-releasing hormone (CRH) syndrome; these ACTH-dependent Cushing's
      syndrome have usually diffusely enlarged adrenal glands. In the second class are
      cortisol producing unilateral adrenocortical adenomas or carcinomas, and the
      recent Cushing's syndrome with food dependent periodic hormonogenesis. This food
      dependent Cushing's syndrome is an ACTH-independent Cushing's syndrome with
      multinodular enlargement of both adrenal glands. Pathogenesis is an aberrant
      adrenal sensitivity to physiologic secretion of gastric inhibitory peptide (GIP).
      Ectopic expression of GIP receptors on adrenal cells involve pathologic food
      induced cortisol secretion. Food dependent Cushing's syndrome is a new cause of
      Cushing's syndrome. Food induced cortisol secretion may have to be explored in
      the ACTH-independent Cushing's syndrome.

PMID- 8758533
TI  - [Hypomagnesemic and hypocalcemic coma, convulsions and ocular motility disorders
      after chemotherapy with platinum compounds].
AB  - We describe a case of neurologic manifestations including coma, convulsion and
      eye movement disorders, associated with hypomagnesemia and hypocalcemia in a
      patient treated with cisplatin for an ovarian adenocarcinoma. Pathophysiological
      mechanisms involve renal tubular damage leading to renal magnesium wasting and
      related hypocalcemia.

PMID- 8758534
TI  - [Thrombosis of the superior mesenteric artery and Behcet's syndrome].
AB  - The authors describe the third case in the literature of superior mesenteric
      artery's thrombosis occurring in the course of the Behcet's syndrome according to
      Mason and Barnes classification. Clinical manifestations in the patient were
      represented by intestinal angor. The literature data concerning vascular
      involvement in Behcet's disease, particularly thrombosis are reviewed. The value
      of noninvasive paraclinic arterial digestive explorations is discussed.

PMID- 8758535
TI  - [Fusaria infection in patients with neutropenia: apropos of 3 cases].
AB  - The authors report three cases of fusarial infection in neutropenic patients with
      hematologic malignancies. The first patient was affected by a cutaneous extensive
      fusariosis. The second patient developed a fusarial lung infection during a
      multiple organ failure following allogenic bone marrow transplantation. The third
      patient who presented with refractory acute myelogenous leukemia, developed
      fusarial skin lesions, and died from pulmonary failure. The treatment of fusarial
      infection is disappointing and requires amphotericin B, in association with
      hematopoietic growth factors. The role of new agents, or combination chemotherapy
      remains to be determinated. The recovery of adequate neutrophil levels is the
      most important factor in the resolution of fusarial infection.

PMID- 8758536
TI  - [Acute intermittent porphyria in 2 Moroccan families. Clinical and biological
      study].
AB  - Three patients from Moroccan kindreds with acute intermittent porphyria (AIP) are
      described. The propositus of family A originating from Mrirt, Morocco, is living
      in Embrun, France. This 26 year-old woman who experienced an acute attack with
      visceral manifestations presented an elevated urinary level of 5-ALA and PBG, and
      a half-normal activity in porphobilinogen deaminase (PBG-D) in red blood cells
      (RBC). The family's survey was carried out by measuring the PBG-D activity in RBC
      (normal values = 125 +/- 40 U). Three of the 16 subjects tested, beside the
      propositus, were found to be asymptomatic carriers (PBG-D < 70 U). The two
      patients of family B, originating from Tetouan in the Rif area, were living in
      Bastia, Corsica. The two brothers, respectively 37 and 39 years old, had a long
      history (6 years) of neuropsychiatric manifestations before the AIP diagnosis was
      evidenced by elevated urinary level of 5-ALA and PBG, and showed a partial
      deficiency, approximately, 50%, of PBG-D activity in RBC. The youngest patient
      also presented a peripheral neuropathy and recently died after surgery from an
      unknown reason at the age of 45.

PMID- 8758537
TI  - [Sarcoidosis of the central nervous system: clinical and radiological
      polymorphism].
AB  - Central nervous system (CNS) neurosarcoidosis was considered to be infrequent.
      Clinical and radiological polymorphism explained the delay before diagnosis. With
      magnetic resonance imaging (MRI), diagnosis is more easily performed, especially
      in paucisymptomatic cases. A review of the most important clinical and
      radiological studies and three personal cases are reported. This underlines
      variable characteristics of hemispheric localizations, especially pseudotumoral
      forms.

PMID- 8758538
TI  - [Use of interferon alpha in multiple myeloma].
AB  - Alpha Interferon has been used for fifteen years in the management of patients
      with multiple myeloma. However this indication remains controversial. Seven
      multicenter randomized trials have compared alpha Interferon with observation in
      patients responding to conventional chemotherapy. Three of these studies have
      given negative results. In the other four, alpha Interferon therapy has prolonged
      remission duration but in none of them has the overall survival been
      significantly prolonged. After intensive treatments the results of only one study
      are available and are in favour of alpha Interferon. Seven randomized studies
      have tested the impact of a combination chemotherapy plus alpha Interferon as
      compared to chemotherapy alone. Only one has shown a significant benefit for
      patients receiving chemotherapy plus natural alpha Interferon. This benefit has
      been limited of IgA and BJ myelomas and to stage II myelomas. Finally, the
      combination high dose dexamethasone-alpha Interferon has given promising
      preliminary results which justify prospective ongoing studies. These clinical
      results are analyzed in relation to the in vitro data.

PMID- 8758539
TI  - [Papular eruption].

PMID- 8758540
TI  - [Hypocalcemia caused by hypomagnesemia during a treatment with cisplatin].

PMID- 8758541
TI  - [Ileocecal tuberculosis and laparoscopic surgery].

PMID- 8758542
TI  - [Eosinophilic fasciitis associated with sarcoidosis: apropos of a case].

PMID- 8758543
TI  - [Temporal epileptic seizures and hyperglycemia: cure of hallucinations with
      insulin].

PMID- 8758544
TI  - [IgG kappa monoclonal gammopathy complicated by AL amyloidosis with symptomatic
      involvement of the temporal artery].

PMID- 8758545
TI  - [Systemic lupus erythematosus, caused by carbamazepine. Apropos of a case].

PMID- 8758546
TI  - [In situ hybridization].

PMID- 8758547
TI  - Human microsporidioses and AIDS: recent advances.
AB  - Microsporidia, unicellular parasites frequent in animals, were rarely reported in
      humans before the advent of AIDS. This immunodeficiency syndrome induces the
      emergence or resurgence of opportunistic infections such as microsporidioses.
      Since 1985, five species of microsporidia have been found in HIV-infected
      patients. One of these species was already known in animals whereas all others
      are new. An increasing number of cases of microsporidioses is detected due to the
      improvement of methods of diagnosis. According to a study conducted in USA,
      intestinal microsporidia appear to be the first cause of diarrhea in patients
      with AIDS. These parasites are intensively investigated as shown by the
      increasing number of studies published since 1993. Most data concern the
      diagnosis, pathology, therapy and epidemiology of human microsporidioses as well
      as the characterization of their agents. Experimental studies aiming to define
      the immune context of these infections are also reported.

PMID- 8758548
TI  - [Cryopreservation of isolates of Toxoplasma gondii in cell culture].
AB  - For a better preservation and identification of Toxoplasma gondii isolates, we
      propose a new method of freezing of toxoplasma growth in THP-1 cell culture. A
      cystogenic strain isolated from foetal blood has been grown in these cells and
      frozen in liquid nitrogen. After thawing, toxoplasma recover the same growth rate
      and morphology in vitro and the same capacity to form brain cysts into mice
      compared to the initial strains. The freezing of the cell suspension provides a
      simple and appropriate method for preservation of Toxoplasma gondii within "bank"
      isolates.

PMID- 8758549
TI  - Canine visceral leishmaniasis in the great Athens area, Greece.
AB  - A survey of 1,175 dogs with suspected visceral leishmaniasis (VL), was carried
      out to investigate canine leishmaniasis in the Athens basin, the largest
      metropolitan area of Greece. The dogs examined were not a random sample since
      animals were selected on the basis of symptoms indicating the disease. Dog sera
      were tested using the indirect fluorescent antibody technique (IFAT), with titres
      greater than or equal to 1/200 considered positive for VL. On this basis 569 dogs
      (48.4%) were found positive for VL and 69 (5.9%) borderline (with titres of
      1/100). Additionally, 218 of these sera were also tested by enzyme-linked
      immunosorbent assay (ELISA). Of this sample, 120 were negative and 88 were
      positive with both IFAT and ELISA (according to the stated criteria), and thus
      the concordance of the two methods was 98.6%. Dogs positive for VL were
      classified according to age, sex, breed, and area of residence. Dogs from
      outlying areas of the Athens basin had higher infection rates than dogs from the
      city. The most affected breed was the Doberman, and the least affected was the
      Collie.

PMID- 8758550
TI  - High prevalence of Ancylostoma spp. infection in dogs, associated with endemic
      focus of human cutaneous larva migrans, in Tacuarembo, Uruguay.
AB  - A helminthological survey of the intestinal parasites in stray dogs was conducted
      in urban and suburban area of Tacuarembo, Uruguay, during winter time. Eighty
      stray dogs captured in the city were necropsied. Seventy nine dogs (98.8%) were
      positive for helminth infection. Seventy seven (96.3%) were parasitized by
      hookworms. Two species of hookworms were found: Ancylostoma caninum 96.3% and A.
      braziliense 49.4%. This is the first report of the prevalence of A. braziliense
      in Uruguay. Considering that incidences of human cutaneous larva migrans caused
      by the migration of hookworms larvae were restricted mainly to the northern part
      of Uruguay and that only A. caninum were reported to be prevalent in the southern
      part, it is supposed that A. braziliense is the primary causative agent of human
      cutaneous larva migrans in Uruguay.

PMID- 8758551
TI  - Taenia multiceps (Cestoda): Ia antigen expression and prostaglandin secretion by
      parasite-modified, murine peritoneal macrophages.
AB  - Taenia multiceps secretions modify accessory cell activity in macrophages. The
      present experiments were designed to elucidate the cellular mechanisms involved.
      While normal, murine peritoneal macrophages amplified mitogen-activated T-cell
      proliferation, macrophages modified by exposure to parasite secretions inhibited
      this proliferation. The modified behaviour was shown by glutaraldehyde-fixed as
      well as living macrophages, and modification was inducible by FPLC fraction 24 of
      coenurus fluid and was associated with an expanded population of 1a- macrophages.
      Secretory products of parasite-activated macrophages also inhibited T-cell
      proliferation, and secretion was prevented by indomethacin. The measurement of
      modified accessory activity was not influenced by the concentration of tritiated
      thymidine in lymphocyte proliferation assays. Consequently there is no evidence
      that the reported events are affected by macrophage-derived, cold thymidine
      secretion. It is concluded that T. multiceps si able to manipulate macrophage
      accessory function by mechanisms which involve altered histocompatibility antigen
      expression and the secretion of prostaglandin.

PMID- 8758552
TI  - Cell surface analysis of trypanosomes of the subgenus Schizotrypanum isolated
      from bats.
AB  - Two stocks (M5, M29) of trypanosomes of the subgenus Schizotrypanum were isolated
      from the bat Phyllostomus hastatus and analyzed for cell electrophoretic mobility
      (EPM) and lectin binding surface sites. Epimastigotes from the M5 and M29 stocks
      presented a mean EPM of around -0.57 and -0.56 microns. s-1.V-1.cm respectively.
      Differences in the agglutination profiles were detected between epimastigotes or
      trypomastigotes from the two parasite populations using lectins with specificity
      for D-GlcNAc, D-GalNAc, D-Gal and D-Man as probe. Major variation was observed
      between epimastigote forms. Additionally, the D-GlcNAc binding lectins WGA and BS
      II strongly interacted with the trypomastigote from both M5 and M29 stocks; this
      fact is evidence that these trypanosomes are distinct from Trypanosoma
      (Schizotrypanum) cruzi.

PMID- 8758553
TI  - [Two cases of hepatic helminthiasis in Marmota monax with hepatitis virus(WHV)
      infection].
AB  - Autopsy of two Woodchuck Hepatitis Virus (WHV) infected Woodchucks, Marmota
      monax, revealed the presence of two parasites in an hepatic localization, Taenia
      mustelae (Larvae) and Calodium hepaticum. The authors present the identification
      of the two parasites, based on the observation of cysticerci of Taenia mustelae,
      or on the observation of the eggs of C. hepaticum. They discuss the probable
      interaction between hepatic parasites and WHV infection.

PMID- 8758554
TI  - Second case of zoonotic Onchocerca infection in a resident of Oita in Japan.
AB  - A non-gravid female Onchocerca was found in histopathological sections of a
      biopsy specimen taken from a painful nodule in the wrist of a 57-year old woman
      in Oita, in southern Japan. Six species of Onchocerca have been found in animals
      in Japan: two in wild bovids, one in equids, and three in domestic bovids of
      which one, Onchocerca sp., is only known by the microfilaria and infective stage.
      Distinctive morphological features of the worm, including a three-layered thick
      cuticle with prominent annular ridges at wide intervals, high somatic muscles and
      narrow lateral chords, resembled those of O. gutturosa, one of the three bovine
      Onchocerca species transmitted in the Oita region. However Onchocerca sp., which
      is also transmitted in this region, cannot be excluded. An ELISA test of the
      patient serum suggests that infections by Onchocerca spp. might be distinguished
      from those by Dirofilaria immitis, of which the number of human cases is
      increasing in Japan.

PMID- 8758555
TI  - Madin Darby canine kidney: a new cell line for Pneumocystis carinii in vitro
      culture.
AB  - Pneumocystis carinii pneumonia (PCP) is a highly frequent cause of morbidity and
      mortality in immunocompromised subjects, particularly in HIV-infected ones. The
      biology of P. Carinii is poorly understood because of the lack of reliable
      synthetic media or adequate cell lines to grow this opportunistic pathogen in
      continuous culture. We reported the suitability of the MDCK (Madin Darby Canine
      Kidney, ATTC CCL 34) cell line to support the temporary microorganism's growth in
      vitro and the experimental pharmacological trials, in comparison with the HEL 299
      cell line, used as reference standard.

PMID- 8758556
TI  - Lack of activity of artemether for prophylaxis and treatment of Toxoplasma gondii
      and Pneumocystis carinii infections in rat.
AB  - Artemisinin and its derivatives have been found effective in vivo against
      Plasmodium and in vitro against Toxoplasma gondii and Pneumocystis carinii. We
      tested the activity of artemether for prophylaxis and treatment in the rat model
      of concurrent T. gondii and P. carinii infection. Artemether at doses of 18 and
      100 mg/kg administered (s.c.) in prophylaxis did not prevent toxoplasmosis or
      pneumocystosis, while trimethoprimsulfamethoxazole (reference treatment) was
      effective for prevention of both infections. Similar results were obtained in
      curative studies. These results do not support the use of artemether for
      prevention or treatment of toxoplasmosis or pneumocystosis.

PMID- 8758557
TI  - [French experience in the closure of atrial septal defects of the ostium secundum
      type with the Sideris button occluder].
AB  - From February 1992 to November 1995, four French teams used the Sideris button
      occluder to close 122 ostium secundum, foramen ovale or surgical fenestration
      atrial septal defects in 121 patients aged 2 to 79 years with body weights of 10
      to 96 kg. a left-to-right shunt in 110 cases (average QP/QS = 2.09) or right-to
      left shunt in 12 cases. The usual type of prosthesis was used in 115 cases, 8
      centered on a guide wire, reverse type in 5 cases and the "centering-device" type
      in 2 patients. Nineteen implantation attempts were abandoned before releasing the
      prosthesis. The immediate results were: closure of the atrial septal defect in
      116 patients: 59 were completely occluded, 43 had minimal residual shunts. Five
      patients were operated for non-buttoning or malposition of the prosthesis. In one
      other case, the device was removed by catheterisation. During follow-up ranging
      from 1 month to 3 years, 20 patients were operated for varying complications, the
      commonest of which was malposition of the prosthesis (17 cases) with a shunt of
      variable volume. In one other case, a second device was inserted. Seventy-seven
      patients were reviewed at 1 year, 28 a 2 years and 6 at 3 years. The residual
      shunts decreased with time but only completely disappeared in half the cases.
      Secondary fractures not requiring surgery were observed in 5 patients. Failures
      and complications were the result of various causes which are discussed.
      Successive technological improvements and the experience of the medical teams
      should reduce this incidence, but caution is required especially in the treatment
      of young children.

PMID- 8758558
TI  - [Percutaneous implantation of endoprostheses in stenosis of the pulmonary
      branches].
AB  - Between July 1992 and October 1995. 10 Palmaz stents were implanted in 6 patients
      aged 2 to 25 years with stenoses of pulmonary artery branches. The stenoses were
      located on the right (n = 2) or left pulmonary artery (n = 3) or both branches (n
      = 1). Stenoses of the right pulmonary artery were secondary to a Waterston (n =
      1) or Blalock-Taussig (n = 1) anastomosis or to surgical plasty with Dacron (n =
      1). Stenoses of the left pulmonary artery were secondary to surgical plasty with
      Goretex (n = 2), pericardium (n = 1) or Dacron (n = 1): three of these patients
      had undergone a left Blalock-Taussig anastomosis before complete correction.
      After implantation of the stent, the pulmonary artery diameter increased from 4
      +/- 2 mm to 11 +/- 2 mm (p = 0.0117) and the transstenotic gradient decreased
      from 44 +/- 18 to 15 +/- 12 mmHg (p = 0.0277). Similarly, the percentage of
      homolateral pulmonary perfusion at scintigraphy increased from 22 +/- 13% to 53
      +/- 17% (p = 0.0431). There were no deaths. The major complication was migration
      of the stent, observed in three patients at the moment of implantation in two
      cases and in the hours following implantation in the other case. In these 3
      patients, the embolised stent was left in the pulmonary arteries with no adverse
      consequences on pulmonary perfusion. Two of these patients later successfully
      underwent further catheterisation for implantation of another stent. Implantation
      of a stent is a therapeutic alternative in pulmonary artery stenoses which often
      recur after surgery and/or angioplasty. They increase the diameter of the
      stenosed vessel and reestablish the equilibrium of perfusion between the two
      lungs.

PMID- 8758559
TI  - [Percutaneous valvotomy of aortic valve stenoses in children].
AB  - A retrospective cooperative study of percutaneous aortic valvuloplasty was
      undertaken in 12 French centres from 1985 and included 90 children over 3 months
      of age (average 8.5 +/- 5.2 years) treated for isolated aortic valve stenosis
      with peak transvalvular pressure gradients of 80.7 +/- 23 mmHg. over 50 mmHg in
      92% of cases. The majority of cases were performed by a retrograde femoral
      arterial approach with inflation of a balloon with a diameter approximating that
      of the aortic annulus. There was one serious complication (lethal collapse
      occurring before dilatation) and 12% of local complications due to arterial
      trauma: the latter were temporary or accessible to simple therapeutic measures.
      Overall, the pressure gradient decreased by an average of 39.2 +/- 25.4 mmHg.
      There were 15 immediate failures (17%) and 21 partial results (23%) requiring a
      further procedure at varying intervals after the valvuloplasty. There were 54
      primary successes (60%) with annulation of the pressure gradient and this result
      was sustained in 45 of the 51 cases followed up for an average of 34 +/- 21
      months. Aortic regurgitation was observed or aggravated in 29 children; at the
      end of the study, this remained a serious problem in 15 cases (17%). The authors
      conclude that interventional catheterisation is an elegant. simple and relatively
      economical alternative to conventional surgery. It is as safe, but less
      immediately effective overall; aortic continence may be compromised in the long
      term. In the absence of technical innovations, a parallel development of the two
      therapeutic procedures is to be expected.

PMID- 8758561
TI  - [Percutaneous dilatation of the pulmonary tract in tetralogy of Fallot].
AB  - When palliative treatment is indicated in tetralogy of Fallot, percutaneous
      endoluminal dilatation of the valvular pulmonary stenosis may represent an
      alternative to palliative surgery (systemico-pulmonary shunt) and its
      disadvantages. This paper sets out the clinical outcome and growth of the
      pulmonary arterial circulation after dilatation of the valvular pulmonary
      stenosis in children with tetralogy of Fallot. Twenty-five children (average age:
      8 +/- 5.8 week; average weight: 6.7 +/- 2.4 kg) were included in this study. The
      dilatation resulted in an immediate decrease in the patients' cyanosis and a
      significant increase (+10%) in arterial oxygen saturation. However, this
      technique did not suppress the risk of anoxic malaise. Only 5 children (20%)
      required a palliative surgical shunt for persistence of anoxic malaise. From the
      anatomical point of view, the dilatation induced significant growth of the
      pulmonary annulus (7.6 mm vs 11.3 mm; p < 0.0001), of the main pulmonary artery
      (6.8 mm vs 10 mm); p = 0.008) and left pulmonary artery (7 mm vs 11 mm; p =
      0.02). The need for a procedure to widen the right ventricular outflow tract at
      the time of complete correction was also reduced. The perioperative mortality of
      complete correction and postoperative pulmonary insufficiency were decreased.
      Percutaneous dilatation of the right ventricular outflow tract is therefore a
      valuable palliative alternative to surgical sytemico-pulmonary shunt.

PMID- 8758560
TI  - [Percutaneous pulmonary valvuloplasty in neonates and infants with tetralogy of
      Fallot].
AB  - Percutaneous pulmonary valvuloplasty remains controversial as a palliative
      procedure in Tetralogy of Fallot. This paper reports the results of this
      technique with respect to clinical improvement and growth of the pulmonary
      arterial tree. Between June 1990 and July 1995, valvuloplasty with a balloon
      catheter was performed in 25 neonates or infants with Tetralogy of Fallot (13
      girls and 12 boys). All patients were symptomatic with severe cyanosis associated
      with anoxic malaise in 14 cases. At catheterisation, the children were aged 3.5
      +/- 2.6 months and weighted 4.7 +/- 1.2 kg. After dilatation, cutaneous oxygen
      saturation increased from 75 +/- 11 to 88 +/- 8% (p = 0.001). However, 3 children
      were referred for early surgery (one complete correction and two systemico
      pulmonary anastomoses because of persistent desaturation. There were no lethal
      complications. A control (catheterisation or surgery) allowed evaluation of the
      growth of the pulmonary tract, on average 5.5 +/- 4.3 months after dilatation.
      The pulmonary artery diameter increased from 6.17 +/- 1.26 mm to 8.66 +/- 1.22 mm
      (p = 0.0015). Expressed as a Z score, the annulus diameter changed from -3.93 +/-
      0.91 to -2.54 +/- 1.2 SD (p = 0.0019). The mean Z score of the right pulmonary
      artery increased from -3.01 +/- 0.69 to -1.98 +/- 1.12 SD (p = 0.0251) and the Z
      score of the left pulmonary artery from -2.68 +/- 0.85 to -1.61 +/- 1.46 SD (p =
      0.0357). At complete correction, 50% of patients had had correction of their
      malformation without section of the pulmonary annulus. In conclusion, pulmonary
      valvuloplasty in Tetralogy of Fallot enables growth of the annulus and pulmonary
      arteries and is a valuable alternative to palliative systemico-pulmonary
      anastomosis.

PMID- 8758562
TI  - [Closure of patent ductus arteriosus by video thoracoscopy in 282 children].
AB  - Closure of patent ductus arteriosus by video thoracoscopy is a standardised
      procedure. The authors report their experience of closure of patent ductus
      arteriosus by video-thoracoscopy from May 1991 to December 1995. The series
      included 282 patients divided into 3 groups according to age: under 6 months (78
      patients, 27.6%), from 6 months to 4 years (135 patients, 42.88%) and over 4
      years of age (69 patients, 24.6%) with an average weight of 12.6 kg (range: 1.2
      to 65 kg). Symptomatic pulmonary hypertension was observed in 39 cases and 9
      children had associated intracardiac malformations (ostium secundum: 3;
      ventricular septal defect: 5; abnormal pulmonary venous drainage: 1) which were
      not corrected. The technique consisted of placing two titanium clips in position
      under video-thoracoscopy to close the ductus. An echo performed immediately
      afterwards confirmed closure of the ductus. The main complications were:
      persistence of a shunt (4 cases) at the beginning of our experience requiring
      immediate reoperation by video-thoracoscopy in 3 cases and by thoracotomy in one
      case; left recurrent laryngeal nerve palsy in 6 cases (2.1%) with regression in 5
      and persistence in one case; one case of postoperative chylothorax which
      regressed rapidly. There were no fatalities or haemorrhages and no blood
      transfusions were required in this series. The average operating time was 20 +/-
      15 minutes and the duration of hospital stay around 48 hours when the patients
      were over 6 months old and 72 hours when less than 6 months of age. Video
      thoracoscopic closure of patent ductus arteriosus is rapid, safe, economical, it
      provides excellent results and may be used in children of all ages.

PMID- 8758563
TI  - [Double outlet left ventricle: a rare and unusual cardiopathy. Apropos of 7 new
      cases].
AB  - Double outlet left ventricle is a very rare condition due to an abnormality of
      conotruncal morphogenesis. The authors report 7 new cases to the 119 already
      published, one with an anatomical variation not previously described. Three of
      the cases reported were of the most usual type similating tetralogy of Fallot.
      Two of these cases underwent complete correction with excellent results 13 months
      and 2 years after surgery. The third patient aged 6 months is well after initial
      palliative neonatal surgery. A case with an L-malposition pedicle with
      subpulmonary ventricular septal defect and pulmonary outflow tract obstruction
      died after early palliative surgery (Blalock-Taussig). A case with subaortic
      ventricular septal defect, pulmonary stenosis, and tricuspid atresia, underwent
      physiopathological correction (Fontan procedure) after a Waterston shunt and is
      well at 19 years of age. The other two cases presented more unusual anatomical
      forms aortic outflow obstruction: one had hypoplasia of the aortic arch with an
      isthmic coarctation requiring a Crafoord procedure in the neonatal period
      associating with banding followed by complete correction at 19 months of age.
      After 3 years, the patient is asymptomatic. The last case with atresia of the
      aortic valve and severe hypoplasia of the ascending aorta died after corrective
      surgery of first intent. Other cases have been described in the literature with
      different clinical presentations: absence of pulmonary or aortic obstruction;
      intact interventricular septum. The anatomical variability is due to the complex
      embryogenesis of the conotruncal region and explains the clinical diversity of
      this congenital cardiac malformation.

PMID- 8758564
TI  - [Pulmonary arborization abnormalities in complex forms of pulmonary atresia with
      ventricular septal defect: unification, unifocalization and complete repair].
AB  - The presence of intrapulmonary arborization abnormalities in patients with
      pulmonary atresia and ventricular septal defect remains a therapeutic challenge.
      The aim of this study was to assess the value of procedures of pulmonary
      unifocalization, i.e. pulmonary unification, remodelling of the central pulmonary
      arteries and creation of an unifocal pulmonary blood supply, thereby resulting in
      complete repair. From october 1989 to october 1995, 27 unifocalization procedures
      were performed in 19 patients. The number of pulmonary segments dependant on non
      communicating systemico-pulmonary collaterals was 14.7 +/- 5.4 per patient. The
      number of non-communicating systemico-pulmonary collaterals was 3.4 +/- 1.2 per
      patient. The Nakata index was 71 +/- 83 mm2/mm2. There were 3 deaths after an
      unifocalization procedure (mortality rate 15.8%). In 12 patients (63.2% of cases)
      a pulmonary arterial tree compatible with a complete repair was obtained. Eight
      complete repairs, with no mortality, following one or several pulmonary
      unifocalization procedures with a right to left ventricular systolic pressure
      ratio of 0.61 +/- 0.12 (range 0.4 to 0.75). Pulmonary unifocalization increases
      the recruitment of pulmonary segments and thereby the possibilities of complete
      correction in forms of pulmonary atresia with ventricular septal defect and
      arborization abnormalities of the pulmonary arterial tree.

PMID- 8758565
TI  - [Surgical treatment of isolated multiple ventricular septal defects. apropos of a
      series of 175 consecutive cases].
AB  - Between January 1980 and September 1995, 175 children were operated for closure
      of isolated multiple ventricular septal defects (VSD) (mean age 20 +/- 8 months,
      mean weight 8.1 +/- 4.4 kg). Eighty-nine patients had pulmonary protection:
      pulmonary artery banding (n = 76) and pulmonary valvular stenosis (n = 13). The
      remainder had severe pulmonary hypertension (mean pulmonary systolic pressures:
      75.7 +/- 20.5 mmHg). The surgical strategy was based on the site of the VSD and
      the ventricular dominance determined preoperatively or at surgery. The VSD were
      perimembranous in 141 cases, muscular in 175 cases, of the inlet septum in 19
      cases and infundibular in 13 cases. A surgical approach through a right atriotomy
      was adequate for complete repair in 122 patients; a second approach was necessary
      by right (n = 35) or left ventriculotomy (n = 4) or both (n = 2) or via the
      pulmonary artery in 2 cases. The operative mortality was 7.4% (13 patients). The
      causes of death were: residual (VSD (n = 6), pulmonary hypertension (n = 2),
      ventricular hypoplasia (n = 2), myocardial infarction (n = 3). Of the 162
      survivors, 33 had residual VSDs, 12 were reoperated once (n = 11) or twice (n =
      1). The mortality was 54.5%. The patients were classified in two groups: Group I
      (n = 130), those operated before 1990, and Group II (n = 45), the ones operated
      afterwards. The low muscular VSDs and left ventriculotomy were risk factors for
      mortality in univariate analysis for Group I and the "Swiss Cheese" type for
      Group II.

PMID- 8758566
TI  - [Long-term outcome of subvalvular aortic stenoses. A comparative study in adults
      and children].
AB  - The aim of the study was to determine the medium and long-term outcome of
      discrete subaortic stenosis after surgery: the data of two groups of patients
      classified according to age (children versus adults) at the time of diagnosis
      were compared retrospectively. Sixteen patients, with subaortic stenosis, were
      followed up clinically and by annual echocardiography for an average period of
      5.7 +/- 3.6 years (range 1 day to 16 years) and patients in group II were aged
      43.6 +/- 6 years (range: 3 to 17 years). Patients in group I were aged 5.4 +/-
      4.2 years (range: 37 to 53 years). Four patients from group II had significant
      aortic incompetence. All but one patient had a membranous stenosis. Seven
      patients from group I and all in group II underwent surgery during the follow-up
      period. Four of the 5 adults in Group II were asymptomatic compared with only 1
      in group I. Three patients of group II developed left ventricular dysfunction
      during the preoperative period compared with none in group I. Four patients in
      group II underwent aortic valve replacement compared with none in group I. Four
      of the 7 operated patients in group I had recurrence of subaortic stenosis, one
      of which was a tunnel form. Two reoperations were necessary in group I. There
      were no recurrences in group II. In conclusion, the poor outcome of adult
      subaortic stenosis has led to early surgical referral. This attitude should be
      nuanced in view of the risk of recurrence and of reoperation in childhood.

PMID- 8758567
TI  - [Cardiac adaptation to muscular exercise in children after complete repair of
      tetralogy of Fallot].
AB  - The aim of this study was to assess cardiac adaptation to muscular exercise in
      children operated for tetralogy of Fallot. Eight children with a history of
      tetralogy of Fallot were studied and compared with ten control children. The
      basal evaluation consisted of an electrocardiogram, spirometry in all cases.
      Chest X-ray and echocardiography in all operated children. A muscular exercise
      stress test with incremental load on a bicycle ergometer was carried out with
      measurement of the cardiac output by CO2 rebreathing (experimental method). Under
      resting conditions, the two groups were comparable with respect to
      anthropometrical parameters and respiratory function. The cardiovascular data
      confirmed the good postoperative results of the children with a history of
      tetralogy of Fallot; cardiothoracic index of 0.49 to 0.55; sinus rhythm on the
      electrocardiogram; right ventricular pressures within normal limits; residual
      instantaneous right ventricular-pulmonary artery pressure gradient less than 25
      mmH. On exercise, there was no significant difference with respect to VO2max,
      maximal heart rate, maximal cardiac output and maximal ventilation. The
      relationship between cardiac output and oxygen consumption was linear in two
      groups: y = 8.17x + 1.95 in the control group, y = 8.57x + 2.82 in the operated
      children. The change in cardiac output on exercise was comparable in the two
      groups. These observations seemed to be related to the good postoperative
      haemodynamic result: absence of pulmonary sequellae and right ventricular
      dysfunction. Despite the normality of the results obtained in this series,
      exercise stress testing with analysis of cardiac and respiratory adaptation would
      seem to be necessary in the follow-up of children operated for tetralogy of
      Fallot to exclude a ventilatory or circulatory limitation.

PMID- 8758568
TI  - [Cardiac output evaluation during exercise in children treated with atrial
      surgery for transposition of great vessels].
AB  - The long-term physiopathological consequences of atrial surgery (Senning or
      Mustard procedures) for transposition of the great vessels with respect to
      exercise capacity are not well known. We measured the cardiac index by the
      technique of CO2 rebreathing at two submaximal levels of exercise corresponding
      to a stable oxygen consumption of 20 (E20) and 30 (E30) ml/min/kg in 7 patients
      successfully operated for transposition of the great vessels and in 7 control
      children paired for age, gender and body surface area. Despite an identical
      chronotropic response to exercise in the two groups, the increase in cardiac
      index was not as great in the children operated for transposition (from 6.86 +/-
      0.51 to 7.71 +/- 0.78 l/min/m2) as in the control population (from 7.71 +/- 0.78
      to 10.2 +/- 0.51 l/min/m2; p < 0.02). The stroke volume index was therefore
      significantly lower in the transposition group at both levels of exercise (52 +/-
      3.2 vs 63 +/- 4.1 ml/m2; p < 0.04 at E20; and 46.4 +/- 4.3 vs 66 +/- 5.1 ml/m2 at
      E30). The main cause of this reduction of the stroke volume index is probably a
      lack of adaptation of right ventricular systolic function on exercise but it is
      not possible to exclude diastolic dysfunction due to reduce compliance secondary
      to the intraatrial patch. The conditions of preload are in fact instrumental in
      increasing stroke volume index at submaximal exercise levels.

PMID- 8758569
TI  - [Cardiac MIBG imaging: a new marker for myocardial function in children?].
AB  - MIBG cardiac imaging is a non-invasive procedure of studying neuronal recapture
      of noradrenaline. In adult cardiomyopathy, abnormal results are observed earlier
      than the increase in circulating catecholamines and constitute a reliable
      prognostic indicator of the disease. The authors assessed this technique in
      children with severe cardiac dysfunction in whom the evaluation of ventricular
      pump function was of primordial importance for the therapeutic decision. Twenty
      eight patients aged 3 months to 20 years (average 6.4 +/- 5.8 years) were
      included in the study. Twenty had hypokinetic dilated cardiomyopathies: with
      respect to the normal values in adults MIGBG uptake was reduced in all cases.
      This alteration was correlated with the severity of myocardial dysfunction
      assessed by echocardiography but is was without doubt the expression of another
      type of physiopathological process. No relationship was observed with the
      aetiology of the cardiomyopathy. Eight children had a single ventricle treated by
      cavopulmonary bypass in 7 cases and by pulmonary artery banding in the other
      case: MIBG imaging did not allow assessment of myocardial function in these
      patients probably because the cavopulmonary bypass denervated the heart and
      thereby changed MIBG uptake independently of the cardiac function. These
      preliminary results are encouraging and should lead to the adoption of MIBG
      imaging as one of the key investigations in the functional evaluation of
      childhood cardiomyopathy and perhaps as an important parameter in the decision of
      transplantation in this indication.

PMID- 8758570
TI  - [Late supraventricular arrhythmia complicating Fontan or cavopulmonary type
      procedures. Apropos of 7 cases].
AB  - The authors report 7 cases of late arrhythmias after atriopulmonary (5 cases) or
      total cavopulmonary (2 cases) bypass procedures. There were 6 cases of atrial
      flutter and one case of atrial tachycardia. The condition presented with cardiac
      failure in 5 cases. In 2 patients, atrial flutter caused syncope or dizziness.
      The arrhythmia was reduced by atrial stimulation (3 cases) or by cardioversion (1
      case). Prevention of recurrence with oral amiodarone was effective in all cases
      but was responsible for secondary effects in 4 cases. In one patient, recurrence
      of atrial flutter was complicated by right atrial thrombosis with cerebral
      embolism. Five patients were reoperated after cardiac catheterisation and
      angiography. Surgery consisted of resection of a stenosis of the anastomosis in
      one case, and the transformation of atriopulmonary anastomosis into a total
      cavopulmonary bypass because of a very dilated right atrium without stenosis in 4
      patients. The immediate postoperative period was complicated by a recurrence of
      the arrhythmia in 3 children not treated by antiarrhythmic therapy. At long-term,
      one patient died 6 months after withdrawal of amiodarone therapy of recurrence of
      atrial flutter. Five of the 6 survivors are treated with amiodarone or a
      betablocker; 3 have had pacemaker implantation for severe bradycardia. Late
      atrial arrhythmias complicating atrio- and cavopulmonary bypass procedures carry
      a risk of cardiac failure and sudden death. When diagnosed, the patient should be
      investigated for stenosis of the anastomosis but severe dilatation of the right
      atrium is often the only finding. After restoration of sinus rhythm, maintenance
      antiarrhythmic therapy should be continued indefinitely.

PMID- 8758571
TI  - [Cardiac involvement in Kugelberg-Welander disease. A prospective study of 8
      cases].
AB  - Kugelberg-Welander disease is a juvenile form of slowly progressive spiral
      amyotrophy in which the incidence of cardiac involvement is difficult to
      appreciate as cases are sporadic. Classically, it presents with atrial
      hyperexcitability with variable degrees of atrioventricular block. In order to
      assess the prevalence of cardiac involvement in this condition, the authors
      undertook a prospective study in 8 patients with Kugelberg-Welander disease. All
      underwent clinical and paraclinical examinations to assess cardiac function and
      rhythm. Doppler echocardiography, myocardial scintigraphy with Thallium 201 and
      Technetium99m, resting ECG. 24 hour Holter monitoring and signal averaged ECG
      were performed in all cases. This unique study detected one patient with
      infraclinical disease of the conduction system who became symptomatic during the
      follow-up period and required definitive cardiac pacing. During the study, one 20
      year old man with Kugelberg-Welander disease was admitted to hospital with
      dilated cardiomyopathy with a fatal outcome. Because of the small number of
      patients and after a review of the literature, this study is to be continued to
      obtain a more accurate evaluation of cardiac involvement in this neuromuscular
      disease.

PMID- 8758572
TI  - [Genetics of hereditary cardiopathies].
AB  - Hypertrophic cardiomyopathy may be secondary to a mutation in the cardiac beta
      myosin heavy chain (14q11-q12), alpha tropomyosin (15q22), troponin T (1q32),
      protein C gene (11p11-q13) or in a non yet mapped gene. A X-linked dilated
      cardiomyopathy may be due to a mutation in the dystrophin gene (Xp21). The long
      QT syndrome may be secondary to a mutation in a potassium channel (7q35-36), an
      alpha subunit of the sodium channel gene (3p21) or in genes not yet identified
      (11p15.5, 4q25-q27). Marfan syndrome is associated to mutations in the fibrillin
      1 gene (15q21.1) and a Marfan-like syndrome with not ocular anomalies was mapped
      to 3p24. Patients with Williams-Beuren syndrome have microdeletions in 7q11,
      whereas in the supravalvular aortic stenosis, the elastin gene which maps to the
      same region, is mutated. In Di George and Shprintzen syndromes but not in
      conotruncal malformations, microdeletions in 22q11 are observed. Heterotaxia can
      be transmitted by 3 types of mendelian inheritance (Xq24-q27.1). Finally, other
      diseases were mapped: Noonan and Holt-Oram syndromes (12q), isolated conduction
      blocks (19q13.3), arrhythmogenic right ventricular cardiomyopathy (14q23-q24),
      total anomalous pulmonary venous return (4p13-q12) and Osler-Weber-Rendu (9q33
      q34.1, 3p22 and 12q1). In the near future, these incoming data will deeply modify
      the cardiovascular field.

PMID- 8758573
TI  - [Importance of intrauterine diagnosis of rudimentary autonomic circulation in an
      acardiac twin].
AB  - Foetal acardia is a major complication of twin pregnancies which endangers the
      life of the healthy twin. The authors report the case of a twin pregnancy with an
      acardiac twin followed up by repeated echocardiography from the 20th week of
      pregnancy until delivery at the 36th week. Despite the presence of a parasitic
      mass, the healthy twin showed no sign of heart failure. Attentive ultrasonography
      of this mass showed a certain degree of autonomic circulation ensured by a
      rudimentary cardiac pump. This case confirms the favorable effect of this finding
      on the healthy twin, moreover, it clarifies some haemodynamic features of the
      parasitic mass: to-and-fro circulation, characteristic of a cardiac pump without
      a valve, anastomoses and competitive flow between the two circulatory systems.

PMID- 8758574
TI  - [Pulmonary vein stenosis. Description of a sutureless surgical procedure using
      the pericardium in situ].
AB  - Pulmonary vein stenosis is a rare cardiac disease associated with a disastrous
      prognosis. Nowadays, it is more often a iatrogenic complication, following
      neonatal surgical repair of total anomalous pulmonary venous drainage (TAPVD). It
      is as well a native congenital anomaly. The responsible histologic lesion is an
      intimal hyperplasia that proliferates to involve the extracardiac segment of the
      pulmonary veins. This lesion tends to be extremely recurrent following surgical
      or angioplastic attempts. A new sutureless surgical technique, that tunelizes the
      pulmonary veins to the left atrium through the pericardium, is described. This
      method was successfully applied in a 2.5 years old child, presenting with
      bilateral stenosis of pulmonary veins, following neonatal repair of a TAPVD. The
      result, controlled 6 months later, by catheterization and angiography was judged
      satisfactory. This new technique, that has to be confirmed by a longer follow up,
      may provide a therapeutic answer to this challenging disease.

PMID- 8758575
TI  - [Anomalous origin of the left main coronary artery from the right coronary sinus
      and trajectory to the great vessels. Value of echocardiography in a child].
AB  - During a routine medical check-up, a pathological electrocardiogram was recorded
      in an asymptomatic 6 year old girl. The demonstration of coronary insufficiency
      by exercise stress testing and sestamib myocardio-scintigraphy led to the
      diagnosis of an anomalous origin of the left coronary artery. This vessel arose
      from the right coronary sinus and continued anteriorly to the main coronary
      artery. The data of the literature suggest that the risk of sudden death and of
      coronary insufficiency is associated with the passage of the left coronary artery
      between the aorta and pulmonary artery. The authors describe the anomalous origin
      of the left coronary artery and its trajectory with respect to the great vessels
      by echocardiography, using a high frequency transducer. The anterior direction of
      the left coronary artery in front of the main pulmonary artery may lead to
      ischaemia on effort even without stenosis at coronary angiography.
      Echocardiography may therefore be useful in children with positive exercise
      stress tests for diagnosing anomalous coronary vessels and their relationship
      with respect to the great vessels.

PMID- 8758576
TI  - [Coronary-cardiac fistula as a cause of tricuspid endocarditis treated by mitral
      homograft].
AB  - The authors report a rare case which is interesting from three points of view:
      tricuspid valve endocarditis in a child complicating a fistula between the right
      coronary artery and right ventricle with negative blood cultures but a positive
      serology for Coxiella burnetii. This mutilating tricuspid endocarditis was
      complicated by multiple pulmonary embolism of the right lung. After two months of
      antibiotic therapy the coronaro-cardiac fistula was closed and the tricuspid
      valve replaced with a mitral homograft. All cases of blood culture negative
      endocarditis require serological investigation to detect intracellular organisms
      which are difficult to diagnose and justify specific prolonged antibiotic
      therapy. Control serological tests are essential in the long-term because of the
      risk of chronic infection, especially in cases with prosthetic intracardiac
      material. Treatment, based mainly on tetracyclines, should be continued for at
      least two years.

PMID- 8758577
TI  - [Should postoperative pain management units be developed in France?].

PMID- 8758578
TI  - [Creation of a committee for pain evaluation and treatment].

PMID- 8758579
TI  - [Combined spinal and epidural analgesia for labor. Prolongation by addition of a
      minidose of clonidine to sufentanil. An initial study].
AB  - The effect of adding a minidose of clonidine to intrathecal sufentanil during the
      early first stage of a painful labour was evaluated in this preliminary open
      label, non-randomised trial. Group 1 received sufentanil 5 micrograms + clonidine
      30 micrograms intrathecally (n = 10) and group 2 only intrathecal sufentanil 5
      micrograms (n = 11). The two groups were not statistically different regard-ing
      age, weight, height, primiparity (67 vs 50%), oxytocin use (37 vs 60%), initial
      cervical dilation (m +/- DS: 2.9 +/- 1.1 vs 2.9 +/- 1 cm) and VAS pain scores (70
      +/- 14 vs 68 +/- 19 mm). In group 1, analgesia was markedly prolonged with a
      reduced variability in duration: 146 +/- 27 min vs 95 +/- 44 min, (P = 0.006).
      VAS pain scores were: 14 +/- 20 vs 19 +/- 13, 1 +/- 3 vs 9 +/- 12, 0 vs 5 +/- 7,
      48 +/- 12 vs 65 +/- 15, five and fifteen minutes after intrathecal injection,
      during maximum efficacy, and at the time additional analgesia was required, in
      group 1 and group 2, respectively. Analgesia evaluated with the VAS pain scores
      was better in group 1 compared with group 2 (P = 0.02) and decreased somewhat
      slower. Side effects, such as hypotension, pruritus and sedation, were not
      statistically different between groups. Nausea and motor blockade did not occur.
      In conclusion, the addition of a minidose (30 micrograms) of clonidine to
      sufentanil 5 micrograms given intrathecally seems to potentiate markedly the
      analgesia obtained during the early first stage of labour.

PMID- 8758580
TI  - [Transtracheal jet ventilation with spontaneous ventilation in neoplastic
      laryngeal dyspnea].
AB  - In six suffocating patients with a severe upper airway obstruction (three
      patients after direct laryngoscopy under general anaesthesia and three patients
      with cervical tumor scheduled for a difficult tracheostomy), jet-ventilation was
      delivered using a transtracheal catheter. The jet-ventilator insufflated oxygen
      only when the tracheal pressure was below a preset value, during spontaneous
      inspiration. During expiration, tracheal pressure increased above the preset
      value, the ventilator stopped the insufflation and the expiratory gases escaped
      through the upper airway. This method corresponds to an inspiratory support
      without intubation. In post-anaesthesia patients, oxygenation and alveolar
      ventilation were improved, allowing the avoidance of tracheostomy. In the other
      patients, tracheostomy was made possible with good surgical conditions under
      general anaesthesia. This method can be applied in conscious patients and allows
      oxygenation of suffocating patients.

PMID- 8758581
TI  - [Cancer pain: beneficial effect of ketamine addition to spinal administration of
      morphine-clonidine-lidocaine mixture].
AB  - OBJECTIVE: To assess the benefit of ketamine addition to a morphine-clonidine
      lidocaine mixture administered continuously by the intrathecal route for the
      treatment of cancer pain. STUDY DESIGN: Case series analysis. PATIENTS AND
      METHOD: Four patients experiencing cancer pain with nociceptive and neuropathic
      components were treated with a continuous intrathecal administration of a mixture
      of ketamine (10 mg)-morphine (1-20 mg)-clonidine (30 micrograms)-lidocaine (20
      mg) in 12 mL of normal saline, injected daily with an infusor (Baxter) pump. This
      treatment, associated with oral administration of sustained release morphine
      (SRM), was extended over 35 to 58 days, until the death of the patients. RESULTS:
      Either the secondary addition of ketamine to the morphine-clonidine-lidocaine
      mixture after the 40th and 15th days of treatment in patients no 1 and 2
      respectively, because of a loss of efficiency of the mixture, or the immediate
      administration of the association of the four agents in patients no 3 and 4
      provided efficient analgesia, unchanged over time, without significant adverse
      effects and allowed a decrease of the SRM doses. CONCLUSION: Ketamine by
      intrathecal route potentiates analgesia obtained with morphine-clonidine and
      lidocaine, while impeding the development of a tolerance vis-a-vis the former.

PMID- 8758582
TI  - [Effects of anesthesia on the lower sphincter of the esophagus].
AB  - The lower oesophageal sphincter (LOS) is the most important structure preventing
      regurgitation of gastric contents, with the risk of tracheobronchial aspiration,
      as it occurs in cases of laryngeal incompetence in connection with general
      anaesthesia. This article reviews anatomical data, means of assessment of the
      sphincter function, as well as the effects of anaesthetic agents and situations
      carrying a high risk of regurgitation and tracheobronchial aspiration.

PMID- 8758583
TI  - [Preoperative evaluation of coronary circulation].
AB  - To define a strategy for coronary circulation assessment is a difficult task as
      most of the studies have been carried out in vascular surgery, as some of them
      are controversial, and as no test has a 100% sensitivity and specificity. However
      patients with high perioperative risk of cardiac events have to be identified, in
      order to intensify medical treatment or to consider myocardial revascularisation.
      A first evaluation is based on history, physical examination and simple tests,
      such as rest electrocardiogram and thorax X-Ray. Additional tests are not
      required when surgery does not elicit a major activity of the cardiocirculatory
      system. Postoperative cardiac risk is low when none of the nine risk factors
      defined by Goldman and/or coronary insufficiency (residual angina elicited by
      minor physical activity, unstable angina, myocardial infarction) are present. The
      problem remains in patients with Goldman risk factors and/or at risk of coronary
      artery disease because of diabetes mellitus, heavy smoking,
      hypercholesterolaemia, arterial hypertension, undergoing major abdominal,
      thoracic or vascular surgery. Preoperative electrocardiographic Holter monitoring
      is still of value, especially in patients with known or supposed ischaemic heart
      disease and unable to make a physical effort. A poor exercise capacity and
      changes in electrocardiographic stress testing are factors of poor prognosis. The
      dobutamine stress echocardiography has a good sensitivity and specificity when an
      effort test cannot be performed. The value of dipyridamole-thallium 201
      scintigraphy could be improved by a quantitative analysis of the number of
      affected segments and territories. Patients with angina or ischaemic episodes on
      continuous electrocardiogram, or with dobutamine echocardiography kinetic
      disturbances and with stress myocardic scintigraphy or stress exercise testing
      abnormalities could undergo a coronarography, in order to consider myocardic
      revascularization prior to surgery.

PMID- 8758584
TI  - [Anesthesia and implantable automatic defibrillator].
AB  - Since the introduction of first generation automatic implantable cardioverter
      defibrillators (AICD) in 1980, an increasing number of such devices have been
      inserted in patients at high risk for sudden death by ventricular tachycardia or
      fibrillation (VT/VF). With the improvement of technology and implanting
      techniques, devices may be inserted at present subcutaneously into the abdominal
      or the thoracic wall, rather than by thoracotomy. The anaesthesist is involved in
      the primary implantation of the AICD and the secondary testing of efficiency.
      Implantation generally requires general anaesthesia and the extension of
      monitoring is guided by the patient's underlying disease(s). The efficiency of
      the implanted system is tested one to two months later in inducing VT/VF under
      general anaesthesia and in determining the defibrillation threshold. The
      anaesthetist may also have to take care of patients with a AICD. For such cases
      the following recommendations can be made: a) gloves should be worn by doctors
      and nurses coming into contact with these patients, in order to limit the risk of
      electrification; b) a ring magnet must be available to inactivate the unit; c) in
      case of external defibrillation, the external paddles should be oriented
      perpendicularly to the line joining the two implanted electrodes; d) AICD should
      be disabled during electrocautery and prior to electroconvulsive therapy; e) the
      assistance of a electrophysiologist may be helpful for the management of these
      patients.

PMID- 8758585
TI  - [Coronary artery bypass with extracorporeal circulation in a patient with
      hemophilia B].
AB  - A 64-year-old patient with factor IX deficiency (Christmas disease) underwent
      quadruple coronary bypass grafting for angina pectoris. Excessive bleeding was
      prevented by infusion of factor IX concentrates from one day before surgery until
      the 19th postoperative day. The surgical procedure and the cardiopulmonary bypass
      were carried out in the same manner as in patients without any haemorrhagic
      disorder. No haemorrhagic complication occurred, neither during nor after the
      operation.

PMID- 8758586
TI  - [Management of suspected heart injuries].
AB  - Penetrating cardiac injury has to be ruled out in any patients with penetrating
      thoracic injuries, even in those with no alterations in vital functions.
      Undelayed echocardiography should be performed to screen for the presence of
      pericardial effusion. The first case underlines the risk of cardiac tamponade if
      the diagnosis is missed. Echocardiography was not performed because no
      echocardiographist was present at the time, and a high suspicion of a neck
      vascular injury existed. Sudden deterioration due to the onset of acute tamponade
      was only reversed by an immediate pericardiocentesis followed by surgical
      haemostasis. The second patient, although stable, had a large echographic
      pericardial effusion. Emergent sternotomy revealed a large amount of blood in the
      pericardial space and two cardiac wounds with one on a coronary artery.
      Penetrating wounds in proximity to the heart, even in a stable patient, require
      aggressive attempts at ruling out a cardiac injury. Immediate echocardiography
      should be systematically performed to screen for pericardial fluid.

PMID- 8758587
TI  - [Laparoscopic cholecystectomy in a patient with Steinert disease].
AB  - Steinert's disease or myotonic myopathy is associated with chronic restrictive
      respiratory insufficiency. A case of a patient with Steinert's disease undergoing
      laparoscopic cholecystectomy, with a full recovery within three days is reported.
      It is concluded that laparoscopic surgery is a possible therapeutic tool in
      patients suffering from a myopathy.

PMID- 8758588
TI  - [Evaluation of the activity of a postoperative analgesia department in a Canadian
      hospital].
AB  - OBJECTIVE: To describe the setting up and the activity of an acute pain service
      (APS). STUDY DESIGN: Retrospective descriptive study including two surveys among
      the nursing staff, the first one eight months after the setting up of the APS and
      the second one ten months later. RESULTS: In the first 19 months, 3,404 patients
      were treated in the APS: 1,456 with patient-controlled analgesia (PCA), 1,299
      with epidural analgesia, 589 with spinal opioids and 60 with continuous nerve
      blocks. The resulting overall incidence of respiratory depression was 0.7%. It
      ranged from 0% with continuous nerve block to 1.2% with PCA. It was at 0.3% with
      epidural analgesia and 0.5% with spinal opioids. Both surveys confirmed that
      nurses had a positive attitude toward the APS, mainly because they believed it
      offered patients significant advantages. Many of them thought that epidural
      analgesia and PCA were likely to impede patient's ambulation and most of them
      agreed that these techniques increased their work load. CONCLUSION: Although the
      incidence of respiratory depression was low among the APS patients, it can
      probably still be decreased by a more refined patient selection. Setting up an
      APS is viewed positively by the nursing staff in spite of some perceived
      disadvantages.

PMID- 8758589
TI  - [Neuroanesthesia and intensive care in subarachnoid hemorrhage caused by aneurysm
      rupture].

PMID- 8758590
TI  - [Subarachnoid hemorrhage caused by aneurysm rupture. Initial management of
      patients].
AB  - Subarachnoid haemorrhage is a severe illness with a high mortality and morbidity.
      Its diagnosis is considered in the case of a brutal, violent and unusual
      headache. It is confirmed rapidly with the conventional techniques such as CT
      scan and lumbar puncture. The main complications (ischaemia, rebleeding,
      hydrocephalus) occur during the first two weeks and are a usual event in case of
      a lack of diagnosis or specialised medical, surgical and radiological management.
      Among the complications, rebleeding badly affects prognosis, and only early
      surgery or interventional radiology may improve the outcome. Delayed ischaemia
      may be prevented by medical management with correction of hypovolaemia and
      administration of calcium antagonists, before and after surgery, particularly
      between the 4th and the 10th day. When signs of ischaemia occur, aggressive
      treatment should be administered in order to improve cerebral perfusion pressure
      and cerebral blood flow. The treatment is aimed to prevent the complications of
      subarachnoid haemorrhage and to establish optimal conditions for surgical and
      radiological procedures.

PMID- 8758591
TI  - [Peroperative risks in cerebral aneurysm surgery].
AB  - The perioperative complications associated with cerebral aneurysm surgery require
      a specific anaesthetic management. Four major perioperative accidents are
      discussed in this review. The anaesthetic and surgical management in case of
      rebleeding subsequent to the re-rupture of the aneurysm is mainly prophylactic.
      It includes haemodynamic stability assurance, maintenance of mean arterial
      pressure (MAP) between 80-90 mmHg during stimulation of the patient such as
      endotracheal intubation, application of the skull-pin head-holder, incision, and
      craniotomy. The aneurysmal transmural pressure should be adequately maintained by
      avoiding an aggressive decrease of intracranial pressure. Once the skull is open,
      the brain must be kept slack in order to decrease pressure under the retractors
      and avoid the risks of stretching and tearing of the adjacent vessels. If,
      despite these precautions, the aneurysm ruptures again. MAP should be decreased
      to 60 mmHg and the brain rendered more slack, in order to allow direct clipping
      of the aneurysm, or temporary clipping of the adjacent vessels. The optimal
      agents in this situation are isoflurane (which decreases CMRO2), intravenous
      anaesthetic agents (inspite their negative inotropic effect, they may potentially
      protect the brain) and sodium nitroprusside. Vasospasm occurs usually between the
      3rd and the 7th day after subarachnoid haemorrhage. It may be seen
      peroperatively. The optimal treatment, as well as prophylaxis, is moderate
      controlled hypertension (MAP > 100 mmHg), associated with hypervolaemia and
      haemodilution, the so-called triple H therapy, with strict control of the filling
      pressures. Other beneficial therapies are calcium antagonists (nimodipine and
      nicardipine), the removal of the blood accumulated around the brain and in the
      cisternae, and possibly local administration of papaverine. Abrupt MAP increases
      are controlled in order to maintain adequate aneurysmal transmural pressure. Beta
      blockers, local anaesthetics administered locally or intravenously, a carefully
      titrated level of anaesthesia, a maintained volaemia play a protective role.
      Cerebral oedema is sometimes already present at the opening of the skull or may
      arise later, due to a high pressure under the retractors, to the surgical
      manipulations of the brain or to brain ischaemia subsequent to temporary
      clipping. Its treatment is aggressive, with intravenous agents, mannitol, deep
      hypocapnia and/or lumbar drainage. Prophylaxis, according to the "brain
      homeostasis concept", is the preferred method to avoid these four peroperative
      accidents. It includes normal blood volume, normoglycaemia, moderate hypocapnia,
      normotension, soft manipulation of the brain and optimal brain relaxation.

PMID- 8758592
TI  - [Anesthesia and intensive care of subarachnoid hemorrhage. A survey on practice
      in 32 centres].
AB  - OBJECTIVE: To assess the current practices in anaesthesia and intensive care in
      patients experiencing subarachnoid haemorrhage (SAH). STUDY DESIGN: Analysis of
      questionnaire sent to the members of the French speaking Association of
      neuroanesthesia and intensive care. METHODS: The survey, performed in the summer
      of 1995, included questions on the composition of the neuroanesthesia team,
      anaesthesia, as well as medical and surgical treatments. RESULTS: Twenty-nine
      French and three non French centers answered the questionnaire. In 14 centers,
      more than 60 SAH had been treated in the previous year. Angiography was performed
      under sedation with a benzodiazepine associated with an opioid (54%). Criteria
      for choosing an endovascular approach were the site of the aneurysm (81%), its
      neck size (42%) and the underlying disease (42%). Anaesthesia was induced with
      either propofol (60%) or thiopentone (40%) associated with an opioid and a muscle
      relaxant. It was maintained with either isoflurane (59%) or propofol (41%).
      Nitrous oxide was often associated (62%). During anaesthesia, nimodipine (84%),
      mannitol (69%), anticonvulsants (47%), dopamine (31%) and lidocaine (9%) were
      also administered. Postoperatively, nimodipine was administered for prophylaxis
      of vasospasm (97%) and transcranial Doppler was employed to diagnose vasospasm
      (50%). Other techniques of care included hypervolaemia (89%), controlled arterial
      hypertension (36%) and haemodilution (36%).

PMID- 8758593
TI  - [Subarachnoid hemorrhage caused by aneurysm rupture. Surgery or embolization?].
AB  - Traditionally the aneurysms of the circle of Willis have been an indication for
      neurosurgery. New technologies of endovascular treatment with electrically
      detachable coils resulted in a different therapeutical concept since four years.
      A series including 140 patients has been treated in our institution from 1
      January 1992 to 31 December 1994, 94 of them presenting with a subarachnoid
      haemorrhage. Out of these 140 patients, 84 were treated with surgery, 51 with the
      endovascular technique, five with surgery after incomplete or unsuccessful
      endovascular treatment. Surgery was indicated in patients presenting early after
      bleeding, devoid of vasospasm, with a favourable Hunt and Hess grading and in
      aneurysms located in the anterior part of the circle of Willis. Endovascular
      treatment was indicated in patients admitted with delay, with severe vasospasm, a
      poor Hunt and Hess grading and in all aneurysms of the vertebrobasilar arterial
      network. Age was of less importance in comparison to the status of the vessels
      for selection of the method of treatment. Giant aneurysms are difficult to treat
      as surgery is faced with the size of the aneurysmal itself and endovascular
      technique with the width of the aneurysmal neck.

PMID- 8758594
TI  - [Endovascular treatment of intracranial aneurysms].
AB  - Major improvements have been achieved in endovascular treatment of intracranial
      aneurysms during the last twenty years. Initial techniques of selective balloon
      occlusion were progressively replaced by the packing of the aneurysmal pouch with
      very small and soft metallic devices, named coils, with controlled detachment. In
      some rare cases, balloon occlusion is still used in order to occlude the parent
      vessel or to reverse the flow, especially in the vertebro-basilar system.
      Essential aims for the anaesthesiologist include: complete immobility of the
      patient throughout the endovascular procedure, systemic anticoagulation in order
      to avoid any thromboembolic complication during and after treatment, prevention
      and/or treatment of vasospasm, precise evaluation of fluid balance during the
      procedure. Our experience is based on 145 aneurysms in 135 patients, treated by
      endovascular route; 91 (63%) of them were revealed by a subarachnoid haemorrhage
      (SAH). Their main locations were: the carotid siphon (33.1%), the anterior
      communicating artery (19.3%), the basilar artery (17.2%) and the middle cerebral
      artery (17.2%). Thirty-seven of these aneurysms (25.5%) were very small in size
      with a diameter less than 4 mm. Total or sub-total (more than 90%) occlusion was
      achieved in 141 aneurysms (90.3%). Thromboembolic complications occurred in eight
      patients (5.9%), neurological sequelae in one. Other treatment-related
      complications included the migration of a coil outside the aneurysm in six cases
      (4.4%) without neurological deficit in one and five ruptures of the aneurysm
      (3.7%) during the procedure with one lethal issue due to the spontaneous bleeding
      of a controlateral arterio-venous malformation. Thirteen patients died (9.6%).
      The cause of the death was related on the initial SAH in 11 of them. The two
      others were both due to rupture: of a second untreated aneurysm in one case and
      of an associated arteriovenous malformation in the second one. At present the
      main indications of endovascular treatment are poor or non indications for
      neurosurgery. Due to the quality of results, endovascular therapy will be more
      and more used in case of ruptured or non ruptured aneurysms.

PMID- 8758595
TI  - [Anesthesia and critical care for endovascular occlusion of ruptured intracranial
      aneurysms with electrically detachable coils].
AB  - The endovascular occlusion of ruptured intracranial aneurysms with electrically
      detachable coils is a therapeutic approach which seems to be a promising
      technique. General anaesthesia is considered as being the most adapted for its
      realisation, as its provides complete immobility and as controlled ventilation
      and extended monitoring offer optimal conditions for undelayed treatment of
      haemorrhagic and thromboembolic complications. The available equipment should be
      the same as that used for conventional surgical treatment of ruptured aneurysms.
      Anticoagulation is required to prevent thromboembolic complications during and
      after the procedure. Most teams administer heparin.

PMID- 8758596
TI  - [Enhancement of cardiac performance for prevention and treatment of delayed
      cerebral ischemia caused by vasospasm].
AB  - Following subarachnoid haemorrhage, delayed cerebral ischaemia from cerebral
      vasospasm remains the most important cause of mortality and morbidity in patients
      with surgically secured aneurysms. Therapy with haemodilution, hypertension and
      volume expansion has been recommended to prevent and treat delayed cerebral
      ischaemia in these patients on the basis of uncontrolled clinical series (level
      of evidence III to V, grade C recommendation). Despite the lack of controlled
      studies, the maintenance of a cardiac index > 3.5 L.min-1.m-2 and a systolic
      arterial pressure between 120 and 150 mmHg before clipping and 160 to 200 mmHg
      thereafter is recommended as a prophylactic or therapeutic measure for vasospasm.
      Close monitoring of neurological and cardiorespiratory status is important to
      avoid neurologic and systemic complications.

PMID- 8758597
TI  - [Pharmacological treatment of vasospasm in subarachnoid hemorrhage].
AB  - Pharmacological treatment of vasospasm in subarachnoid haemorrhage (SAH) is
      founded on prevention and treatment of arterial narrowing and delayed ischaemic
      deficits. Safety and efficacy of different agents have been studied and trials
      classified according to the level of evidence proposed by the "Stroke Council" of
      the American Heart Association. Early intracisternal fibrinolysis can prevent
      vasospasm (level III to V of evidence, grade C). Pharmacological treatment is
      based on few drugs. Nimodipine reduces poor outcome related to vasospasm, but
      does not affect angiographic vessel caliber (level of evidence I and II, grade
      A). Its use is strongly recommended. Nicardipine decreases symptomatic and
      angiographic vasospasm, but does not affect outcome (level of evidence I to V,
      grade B). Tirilazad associated with nimodipine prevents delayed ischaemic
      deficits due to vasospasm and improves outcome in male patients. Intra-arterial
      infusion of papaverine associated with transluminal angioplasty can improve
      symptomatic vasospasm, resistant to conventional therapy (level of evidence IV to
      V, grade C). Pharmacological treatment of vasospasm associated with specific
      management founded on pathophysiology of SAH has improved patients outcome.

PMID- 8758598
TI  - [Pharmacological therapeutic prospects of cerebral vasospasm].
AB  - New therapies of cerebral vasospasm aim to prevent the effects of subarachnoid
      haemorrhage. These effects result in red blood cell haemolysis and release of
      oxyhaemoglobin, free radicals formation and lipid peroxidations, imbalance in
      endothelial modulation of vasomotor tone and activation of the complement system.
      Low doses of fibrinolytic agents administered intrathecally accelerate the
      fibrinolysis of the clot and reduce the oxyhaemoglobin release. The tissue-type
      plasminogen activator has proven to be effective in preventing vasospasm, but the
      modalities of this therapy remain to be defined. Free radical reactions may be
      inhibited by free radical scavengers and inhibitors of lipid peroxidations.
      Tirilazad is a potent inhibitor of lipid peroxidations, which improves the
      patients' outcome and has gone to Phase III human trials. Superoxide dismutase
      and tropolone derivatives are currently evaluated in animal models. Vasomotor
      tone can be modified in experimental models either by blocking endothelin
      receptors (BQ-123), or by facilitating the release and enhancing the effect of
      nitric oxide using protein kinase C inhibitors, drugs that increase intracellular
      calcium (cyclopiazonic acid, LP-805) and free radicals scavengers (superoxide
      dismutase). These possibilities are being investigated. Finally, preliminary
      studies have demonstrated the efficacy of FUT-175, an inhibitor of the complement
      system, in the prevention of vasospasm. In the next years, these new therapies
      have to be validated by prospective and randomized clinical trials to propose
      guidelines for the management of patients at risk of cerebral vasospasm after
      aneurysmal rupture.

PMID- 8758599
TI  - [Endovascular treatment of vasospasm].
AB  - Various therapeutic strategies have been recently proposed to prevent the
      vasospasm after subarachnoid haemorrhage, and to avoid its clinical consequences.
      Despite these progresses, mortality and morbidity of delayed ischaemic
      consequences of vasospasm remain important. Two endovascular treatments have been
      proposed. The successful use of transluminal angioplasty for vasospasm was first
      reported by Zubkov in 1984. Transluminal angioplasty is very effective with
      clinical improvement when the treatment is undertaken without delay after the
      onset of symptoms. Limitations of this technique are the inaccessibility of
      distal arteries and the risks (vascular rupture or occlusion). More recently, to
      overcome these limitations, a selective intraarterial infusion of papaverine has
      been proposed. These infusions are less risky and can be employed in distal
      vasospasm. However, clinical results seem to be less favourable and often
      transient. These two techniques are still used with slightly different
      indications. According to our experience, it seems reasonable to reserve
      transluminal angioplasty for symptomatic vasospasm, associated with papaverine or
      not, and to use papaverine alone in all other cases.

PMID- 8758600
TI  - [Difficult intubation in cesarean section is a reality!].

PMID- 8758601
TI  - [Right bronchial rupture during intubation with carlens tube].

PMID- 8758602
TI  - [Arterial catheterization and invasive monitoring of blood pressure in children].

PMID- 8758603
TI  - [Staphylococcus aureus meningitis after obstetrical epidural anesthesia].

PMID- 8758604
TI  - [Intrathoracic venous injury from high pressure water jet].

PMID- 8758605
TI  - [Wandering pacemaker].

PMID- 8758606
TI  - [Non vascular pulsatile exophthalmos complicating head injury].

PMID- 8758607
TI  - [Impact factor: reliable "audimat" of scientific journals].

PMID- 8758608
TI  - Physiotherapy and occupational therapy for juvenile chronic arthritis: custom and
      practice in five centres in the UK, USA and Canada.
AB  - Physiotherapy and occupational therapy are widely accepted as being of central
      importance for the treatment of juvenile chronic arthritis (JCA). However, these
      approaches have rarely been subject to critical scrutiny. The aims of this report
      are to highlight some of the inter-centre similarities and differences observed
      in the implementation of physical and occupational therapy for JCA, and to
      emphasize the need for scientifically controlled research in this area. During a
      series of visits to several paediatric rheumatology units in the UK, USA and
      Canada, three aspects of the service were noted: treatment philosophy, physical
      interventions used for the treatment of JCA and quality-of-life and independence
      training activities. There was general consensus with the philosophy that early
      physical intervention was a vital part of the treatment plan for JCA, although
      all therapists were concerned that compliance with treatment modalities was poor.
      Differences between units in the approach to acute arthritis, the use of foot
      orthoses and wrist splints, the treatment of joint contractures and the use of
      general quality-of-life training activities were noted. Although it was widely
      recognized that controlled research into the efficacy of physical intervention
      was needed, no centre had a co-ordinated plan for such investigations.

PMID- 8758609
TI  - Heterotopic ossification complicating long-term sedation.

PMID- 8758610
TI  - Scurvy, osteoporosis and megaloblastic anaemia due to alleged food intolerance.

PMID- 8758611
TI  - Low-dose corticosteroids and blindness in giant cell arteritis.

PMID- 8758612
TI  - Cardiac abnormalities in a patient with localized scleroderma.

PMID- 8758613
TI  - Evaluation of persons of varying ages.
AB  - Dual coding theory (Paivio, 1986) suggests that communicating a stimulus person's
      age verbally/abstractly through words and numbers arouses little feeling and has
      little effect on the way others evaluate her or him, whereas communicating age
      nonverbally/concretely through facial photographs arouses more feeling and has a
      greater impact on evaluation. Two experiments reported in this article, involving
      U.S. students and incorporating techniques developed in prior research by Levin
      (1988) strongly support these theoretical expectations.

PMID- 8758614
TI  - Coping styles among adolescent competitive athletes.
AB  - The use of approach and avoidance coping styles and task-focused and emotion
      focused coping strategies in competitive sport was explored. Four hundred twenty
      one adolescent males from New South Wales, Australia, who were currently
      competing in team sports indicated their usual responses to each of 8 acute
      stressors commonly experienced in sport, using a 128-item inventory. The
      reliability coefficient (Cronbach's alpha) for each stressor ranged from .81 to
      .92. Twenty-six of the original 128 items on the inventory were retained, on the
      basis of factor analysis. Correlations between stressors indicated that coping
      styles were a function of type of stressor, providing support for the
      transactional model. Goodness of fit was high (.87). The present results
      partially support the construct of coping style among adolescent-aged sports
      competitors.

PMID- 8758615
TI  - Conservative orientation as a determinant of hopelessness.
AB  - Conservative orientation is identified with reference to authoritarianism, work
      ethic belief, just world belief, and endorsement of individualistic causes of
      social problems. This over-arching orientation is hypothesized to affect
      hopelessness and to be affected by self-esteem with reference to ego development
      theory and learned helplessness theory. Causal modeling of data obtained from 1st
      year college students (N = 556) in Hong Kong supports the hypotheses, showing
      that a student's hopelessness relates to his or her conservative orientation,
      even when self-esteem is controlled. This relationship can be interpreted by ego
      development and learned helplessness theories and cannot be explained as a
      spurious effect. Through the theories, hopelessness is interpreted as a result of
      maladaptive development and fatalistic, alienated, and helpless outlooks. This
      maladaptive development and the outlooks in turn result from students'
      conservative and individualistic orientation.

PMID- 8758616
TI  - Conformity in the Asch task as a function of age.
AB  - The social conformity paradigm of Asch (1956) was replicated to investigate the
      relationship between age and conformist behavior. One hundred ten Australian
      school children and adolescents between 3 and 17 years of age participated in the
      study. Each participant was placed in the position of being a minority of 1
      against a wrong but unanimous majority of 3. The results indicate that conformity
      decreases with age in perceptually unambiguous tasks. Conflicting evidence from
      earlier studies can be attributed to task ambiguity in those studies.

PMID- 8758617
TI  - An attributional analysis of suicide.

PMID- 8758618
TI  - Effects of sexual orientation of interviewer on expressed attitudes toward male
      homosexuality.

PMID- 8758619
TI  - Social class and self-esteem.

PMID- 8758620
TI  - The Milgram obedience experiment: support for a cognitive view of defensive
      attribution.

PMID- 8758621
TI  - Men's and women's self-estimates of intelligence.

PMID- 8758622
TI  - Preemployment predictors of children's union attitudes: the moderating role of
      identification with parents.

PMID- 8758623
TI  - Characterization of casein phosphopeptides prepared using alcalase: determination
      of enzyme specificity.
AB  - Tryptic casein phosphopeptides containing the cluster sequence-Ser(P)-Ser(P)
      Ser(P)-Glu-Glu- have been shown to stablize amorphous calcium phosphate at
      neutral and alkaline pH and be anticariogenic in various in vitro, animal and
      human experiments. Furthermore, metal ion complexes of the casein phosphopeptides
      (CPPs) have potential as dietetic supplements to increase the bioavailability of
      calcium, iron, and other essential metal ions. In this study, we have used a
      Ca2+/ethanol selective precipitation procedure to produce a range of
      phosphopeptides from an alcalase digest of whole casein. The CPPs released by
      alcalase were truncated relative to those which are released by trypsin. The
      peptides could be grouped into those containing the cluster sequence as well as
      the group of tri-, di-, and monophosphorylated peptides. The two groups contained
      a number of homologous peptides of varying lengths resulting from the broad
      specificity of alcalase. Alcalase was observed to cleave peptide bonds on the
      carboxyl side of Glu, Met, Leu, Tyr, Lys, and Gln; however, of the twenty-six
      different cleavage sites, seventeen contained a Glu in the P1 position and of
      these, fifteen contained a hydrophobic residue in either the P2' or P3'
      positions. Furthermore, of the twenty-six cleavage sites identified, twenty-two
      contained a hydrophobic residue in either the P2' or P3' positions. Of the four
      other sites cleaved by alcalase, two contained a hydrophobic residue in the P1'
      position and one a hydrophobic residue in the P1 position.

PMID- 8758624
TI  - Effects of driving pressure and recurrent laryngeal nerve stimulation on glottic
      vibration in a constant pressure model.
AB  - Glottic phonatory parameters have been studied in constant flow models; however,
      the lung-thorax system is better viewed as a constant pressure source. Adjusting
      the driving pressure and recurrent laryngeal nerve stimulation as independent
      variables, rather than as dependent variables, may provide a more physiologic
      understanding of laryngeal function and glottic parameters, including subglottic
      pressure, airflow, fundamental frequency, and glottic area. In three dogs
      subglottic pressure and airflow were measured in two separate conditions: with
      constant recurrent laryngeal nerve stimulation and varying driving pressure, and
      with constant driving pressure and varying recurrent laryngeal nerve stimulation.
      Videostroboscopic measures on four dogs assessed glottic areas with constant
      recurrent laryngeal nerve stimulation at different driving pressures. With
      constant recurrent laryngeal nerve stimulation, increasing driving pressure had
      no effect on glottic areas, whereas subglottic pressure, fundamental frequency,
      and airflow increased significantly. However, changes in subglottic pressure were
      minimal in comparison with changes in driving pressure. At constant driving
      pressure, increasing recurrent laryngeal nerve stimulation increased subglottic
      pressure and fundamental frequency and decreased airflow. These findings suggest
      that during phonation subglottic pressure is primarily dependent on recurrent
      laryngeal nerve stimulation and laryngeal muscular contraction, but not on lung
      driving pressure.

PMID- 8758625
TI  - Anosmia and chronic sinus disease.
AB  - Chronic sinus disease associated with progressive mucosal disease is often a
      cause for anosmia. Despite aggressive allergic, medical, and surgical
      intervention, long-term relief of anosmia has been difficult to document. Fifty
      patients sought treatment for subjective anosmia and symptoms of progressive
      sinusitis and underwent endoscopic sinus surgery. After surgery 52% maintained
      significant improvement in smell by subjective measures that correlated with
      objective olfactory University of Pennsylvania Small Identification test
      ("UPSIT") results. Of the remaining patients, some had intermittent improvement,
      but most remained hyposmic or anosmic despite clinically well-healed ethmoid
      surgical beds. Of the preoperative and postoperative historical, clinical, and
      radiological data analyzed, severity of the presenting sinus disease (defined as
      stage II In the Kennedy staging criteria or disease extending beyond the ethmoids
      on preoperative computed tomography scan) and persistent mucosal disease in the
      surgical bed are associated with persistent anosmia (p = 0.005).

PMID- 8758626
TI  - Chondrosarcoma of the nasal septum: skull base imaging and clinicopathologic
      correlation.
AB  - Chondrosarcoma arising in the head and neck and craniofacial region is an
      uncommon lesion. The nasal septum is a particularly rare site of origin, with
      approximately 30 cases previously reported in the English literature. We present
      six new cases of chondrosarcoma arising in the nasal septum. Each of these tumors
      required cranial base surgical approaches for removal. Current imaging techniques
      allow a very accurate diagnosis to be made before biopsy. The characteristic ring
      forming calcifications seen on computed tomography scans can be correlated with
      the histologic pattern of calcification. Magnetic resonance imaging techniques
      allow precise definition of tumor extent, which is particularly important because
      the disease is best treated with primary surgery. Advances in imaging and
      surgical techniques allow a much more complete tumor removal. It is hoped that
      this will increase the likelihood of cure in these patients. Surgical management
      and indications for adjuvant therapy are discussed.

PMID- 8758627
TI  - Receptors for glucocorticoids in the human inner ear.
AB  - Glucocorticoid receptors were detected in the human inner ear. The highest
      concentration of glucocorticoid receptor protein was measured by enzyme-linked
      immunosorbent assay in the spiral ligament tissues; the lowest concentration of
      glucocorticoid receptors was measured in the macula of the saccule. The
      demonstration of the presence of glucocorticoid receptors in human Inner ear
      tissues provides a basis to consider the direct effects of glucocorticoid action
      on select inner ear cells, rather than assuming a systemic antiinflammatory or
      immunosuppressive effect during the therapeutic treatment of patients with given
      inner ear disorders.

PMID- 8758628
TI  - Correlation of modified radioallergosorbent test scores and skin test results.
AB  - In addition to a significantly increased sensitivity as compared with the initial
      Phadebas radioallergosorbent test, a major advantage of the Fadal-Nalebuff
      modified RAST is its correlation with skin testing using skin end point
      titration. This correlation allows physicians to use both these modalities in the
      diagnosis and treatment of allergic disorders. However, it has been anecdotally
      believed that the correlation of radioallergosorbent test classes and skin test
      end points varied somewhat with different antigens. Fifty-three patients were
      tested by radioallergosorbent test for 12 inhalant antigens common to the North
      Texas region. These patients subsequently underwent confirmation of their
      radioallergosorbent test results by application of intradermal tests at a
      concentration of one fivefold step weaker than the corresponding
      radioallergosorbent test level (a "RAST minus one" dilution). The relationship
      between radioallergosorbent test and skin test results will be critically
      analyzed.

PMID- 8758629
TI  - Enhanced retrosigmoid exposure with posterior semicircular canal resection.
AB  - A subset of patients with acoustic neuromas and useful hearing have tumors that
      are inadequately approached by both middle fossa and retrosigmoid techniques. The
      enhanced retrosigmoid technique combines the hearing preservation of posterior
      semicircular canal ablation to achieve lateral internal auditory canal exposure
      with the ample cerebel-lopontine angle exposure of the standard retrosigmoid
      technique.

PMID- 8758630
TI  - Aspergillus sinusitis: clinical aspects and treatment outcomes.
AB  - Seventy-two cases of Aspergillus sinusitis were analyzed during a period of 14
      years from January 1980 through October 1993. There were 60 cases of primary type
      and 12 cases of secondary type. The maxillary and ethmoid sinuses were most
      commonly affected in both primary and secondary types. The sphenoid sinus was
      commonly involved in secondary type. Fourteen (23%) cases of primary type and 4
      (33%) cases of secondary type demonstrated sinus wall destruction on computed
      tomography or magnetic resonance images. Seventy percent of primary type and all
      cases of secondary type showed focal or diffuse areas of increased attenuation in
      the soft tissue mass on computed tomography scans. Sixteen cases assessed by
      magnetic resonance imaging showed decreased signal intensities on T1-weighted
      images and markedly reduced signal intensities on T2-weighted images. Fifty-nine
      (98%) of 60 cases of primary type were noninvasive, and 1 was invasive. In
      secondary type, 10 (83%) of 12 patients had noninvasive disease. The most common
      coexisting disease in secondary aspergillosis was diabetes mellitus. Thickened
      mucosa with necrotic brownish green material, which was the most common finding
      in both types, was found in 33 patients with primary type and in 5 with secondary
      type. Surgery was performed in most cases, among which 4 patients received
      chemotherapy after surgery with amphotericin B with or without flucytosine. All
      patients were cured without recurrence during a mean follow-up period of 13
      months.

PMID- 8758631
TI  - How to systematically review the medical literature.
AB  - In contrast to traditional narrative reviews, systematic reviews are true
      hypothesis-driven research. Meta-analysis is a form of systematic review in which
      studies are selected and combined by use of a predefined protocol to reduce bias
      and subjectivity. A sensitivity analysis shows how results vary through the use
      of different assumptions, tests, and criteria. The most valid synthesis of
      information occurs when published and unpublished materials are subjected to the
      same rigorous evaluation and when results are calculated with and without
      unpublished sources of data. A good systematic review captures the reader's
      attention through a skillful blend of numbers and narrative and qualifies for
      publication as original research in a peer-reviewed journal. Otolaryngologists
      have published systematic reviews of varying quality since 1990. This article
      should help improve the quality and validity of future efforts.

PMID- 8758632
TI  - Nasal septum after sublabial transseptal transsphenoidal pituitary surgery.
AB  - Transseptal transsphenoidal approach to the pituitary fossa is a well-described
      and effective procedure. This article relates our experience with this procedure
      with specific emphasis on the nasal septum, both before and after surgery. It has
      been our experience that this surgery has minimal local complications in the nose
      and it would appear to improve septal alignment with subjective improvement in
      nasal function as reported by the patient. A total of 55 patients undergoing a
      sublabial transseptal transsphenoidal approach to the pituitary fossa were
      included in this study. All other approaches to the pituitary gland were
      excluded. Visual changes and headaches were the most common presenting symptoms,
      occurring alone or in combination in 28 (51%) patients. Twelve (22%) patients
      reported symptoms of nasal obstruction before surgery and only one (2%) after
      surgery. A moderately or severely deviated septum was noted in 30 (54%) patients
      before surgery and 4 (7%) patients after surgery. The septum was straight in 21
      (38%) patients before the procedure and 49 (89%) patients after the surgery.
      Sinusitis developed in two patients, and one patient subsequently required
      surgery. No synechiae or septal perforations were noted.

PMID- 8758633
TI  - Vestibular deficits in deaf children.
AB  - Considerable knowledge has been accumulated regarding acquired and congenital
      deafness in children. However, despite the intimate relationship between the
      auditory and vestibular systems, data are limited regarding the status of the
      balance system in these children. Using a test population of 15 children, aged 8
      to 17 years, we performed electronystagmography testing. The test battery
      consisted of the eye-tracking (gaze nystagmus, spontaneous nystagmus, saccade,
      horizontal pursuit and optokinetic) tests, positional/positioning (Dix-Hallpike
      and supine) tests, and rotational chair tests. With age-matched controls, five
      children were tested in each of the following three categories: normal hearing,
      hereditary deafness, and acquired deafness. The children in the hereditary
      deafness category were congenitally deaf and had a family history of deafness.
      Those subjects in the acquired deafness category had hearing loss before the age
      of 2 years, after meningitis. Analysis of variance demonstrated significant
      differences between the two deaf groups and the control subjects in the gaze
      nystagmus test, saccade latencies, horizontal pursuit phase, and Dix-Hallpike and
      supine positionally provoked nystagmus. Also, significant differences were found
      in rotational chair gain and phase between the deaf and normal-hearing children.
      The children with acquired deafness exhibited the most profound results. In
      addition, there were significant differences in rotational chair gain between the
      acquired and congenitally deaf children. No differences were noted in horizontal
      pursuit gains, saccade accuracies, or saccade asymmetries. These preliminary data
      demonstrate that the etiologic factors responsible for congenital and acquired
      deafness in children may indeed affect the balance system as well. These findings
      of possible balance disorders in conjunction with the profound hearing loss in
      this patient population will have prognostic implications in the future
      evaluation, treatment, and rehabilitation of these patients.

PMID- 8758634
TI  - Long-term follow-up of stapedectomy in children and adolescents.
AB  - Otosclerosis presenting in children and adolescents is uncommon. Typically,
      otosclerosis presents as a slowly progressive conductive hearing loss in the
      third to fourth decade. Many well-documented studies have demonstrated excellent
      long-term hearing results with stapedectomy. Although stapedectomy is highly
      effective, the rare complications may be devastating. Thirty-one patients, 21
      years or younger, underwent 40 stapedectomies for otosclerosis at our
      institution. The average age at surgery was 16 years, with a range of 7 to 21
      years. Postoperative results showed an average improvement in air-bone gap of 22
      dB. Clinical and audiologic data were collected over a mean follow-up period of
      25 years. There was no statistically significant difference in air-bone gap when
      comparing the immediate postoperative gap (measured 2 months after stapedectomy)
      with the last gap recorded (mean, 25 years after stapedectomy). Fifty percent of
      the ears operated on maintained an air-bone gap within 10 dB at the last follow
      up, and an additional 40% maintained a 10- to 20-dB gap. There were no
      significant relationships between demographic or clinical factors and "success"
      (gap <= 10 dB) or long-term gap closure. Our data demonstrate that stapedectomy
      is an effective method for closing the air-bone gap in children and adolescents
      with otosclerosis, and long-term results parallel those of adults, showing
      maintenance of excellent gap closure. This review represents the largest
      population with the longest follow-up in children who underwent stapedectomy for
      the treatment of otosclerosis.

PMID- 8758635
TI  - Anterior facial nerve rerouting in cranial base surgery: a comparison of three
      techniques.
AB  - Anterior rerouting of the facial nerve is a maneuver designed to enhance exposure
      of the jugular foramen and carotid canal during resection of cranial base tumors.
      Our clinical impression is that the degree of additional exposure afforded by
      moving the facial nerve varies considerably according to both anatomic variations
      and the technique used. Three possible techniques exist based on the extent of
      facial nerve mobilization and point of rotation: canal wall up-second genu pivot
      point (CWU-2G); canal wall down-second genu pivot point (CWD-2G); and canal wall
      down-first genu pivot point (CWD-IG). We anatomically studied 20 human cadaver
      heads to establish clinically relevant guidelines for the selective use of these
      techniques. At the level of the dome of the jugular bulb, the facial nerve
      mobilized anteriorly a mean of 4.2 mm for CWU-2G, 10 mm for CWD-2G, and 14 mm for
      CWD-1G. Detailed analysis of numerous measurements and rotation angles suggests
      that the typical exposure afforded by the various rerouting techniques is as
      follows: CWU-2G, complete exposure of the jugular bulb; CWD-2G, exposure of the
      jugular bulb and a mean of 6 mm of the posterior aspect of the carotid artery;
      and CWD-IG, exposure of the jugular bulb and entire carotid genu. Minimizing the
      amount of facial nerve manipulation needed to achieve sufficient surgical
      exposure helps optimize postoperative functional status.

PMID- 8758636
TI  - Universal newborn screening for hearing loss: ideal vs. reality and the role of
      otolaryngologists.
AB  - In 1993 the National Institutes of Health Consensus Statement, Early
      Identification of Hearing Impairment in Infants and Young Children, recommended
      "universal screening for hearing impairment prior to three months of age."
      However, the decision to invoke screening programs that include all newborns
      remains highly controversial, even though such programs now exist in at least 60
      hospitals in 18 states. Unfortunately, otolaryngologists in the United States
      have not been actively involved in this ongoing debate, despite the role of those
      in our specialty as "gatekeepers" of hearing loss in patients of all ages. In
      relation to identification of hearing loss in the neonatal period, we have
      abrogated our responsibility to other health care professionals.
      Otolaryngologists, this is your "wake up call."

PMID- 8758637
TI  - Processing of adenoid and tonsil specimens in children: a national survey of
      standard practices and a five-year review of the experience at the Children's
      Hospital of Pittsburgh.
AB  - The best means of pathologically examining routine tonsillectomy and
      adenoidectomy specimens in children remains controversial. Otolaryngologists fear
      missing an unsuspected diagnosis. However, the cost-effectiveness of microscopic
      analysis, given the rare incidence of unsuspected diagnosis, is questionable. If
      a significant pathologic diagnosis is missed, the medicolegal implications could
      be significant. A questionnaire was sent to 111 members of the American Society
      of Pediatric Otolaryngology. Additionally, we reviewed our experience at the
      Children's Hospital of Pittsburgh for the 5-year span from 1989 to 1994 to
      determine our incidence of unsuspected pathologic diagnoses. Sixty-five
      questionnaires were returned (59% response rate). More than half (56%) of the
      respondents stated that microscopic analysis was routinely performed on all
      specimens, and 42% replied that only gross examination was performed, reserving
      microscopic examination for selected cases. Three respondents said that they
      discarded their specimens in the operating room. From March 1989 to October 1994,
      in 1985 children undergoing bilateral tonsillectomy and adenoidectomy at the
      Children's Hospital of Pittsburgh, no significant pathologic diagnoses were
      found. Twenty-seven additional children who underwent only tonsillectomy between
      January 1991 and October 1994 were also reviewed. One lymphoma, suspected before
      surgery, and a glycogen storage disorder, not suspected before surgery, were
      diagnosed. Therefore, in a total of 2012 children, we found only one clinically
      significant unsuspected diagnosis. In conclusion, we found no national consensus
      governing the best way to examine routine adenotonsillectomy specimens in
      children. Given that unsuspected diagnoses are rare, reserving microscopic
      analysis for specific clinical indications may be both more cost-effective and
      medically feasible.

PMID- 8758638
TI  - Intraoperative auditory monitoring in acoustic neuroma surgery.
AB  - Intraoperative auditory monitoring is a useful adjunct that is currently
      evolving. Near-field monitoring techniques such as electrocochleography and
      direct eighth nerve compound action potential are being used more frequently. The
      use of these two techniques is compared in 26 patients undergoing hearing
      preservation acoustic neuroma resection. Overall, 9 (35%) of the 26 patients had
      their hearing preserved. Three (23%) of the 13 with electrocochleography
      monitoring and 6 (46%) of the 13 with direct compound action potential monitoring
      had hearing preserved after surgery. Although there was a suggestion of improved
      results with direct compound action potential monitoring, the results were not
      statistically different. It was noted that lack of electrical response at the
      completion of the procedure (regardless of monitoring technique) was correlated
      with poor postoperative hearing, whereas the presence of a waveform at
      termination in no way predicted satisfactory postoperative hearing. The two
      techniques and their advantages and disadvantages are discussed.

PMID- 8758639
TI  - Pediatric cholesteatoma: an individualized, single-stage approach.
AB  - We report our experience with a one-stage surgery for pediatric cholesteatoma in
      216 ears. Our technique is based on three main principles: (1) the surgery is
      individualized; (2) the goal of surgery is to completely remove cholesteatoma and
      related disease in one operation; and (3) the reconstruction is performed to
      provide both good hearing and a dry, trouble-free ear. The incidence of
      recidivism was 10.2%, and the rate achieved was 13.3% at 5 years and 24% at 10
      years. Canal wall down surgery was the predominant procedure used. The incidence
      of intraoperative neurosensory hearing loss, vertigo, and facial nerve injury was
      extremely low. The postoperative cavity problems encountered were minimal.

PMID- 8758640
TI  - Allergic rhinitis: clinical practice guideline. Committee on Practice Standards,
      American Academy of Otolaryngic Allergy.

PMID- 8758641
TI  - Otolaryngology and the Internet.
AB  - During the past 25 years, the Internet has grown tremendously. Starting as four
      academic computers linked by the Department of Defense, it has become a major
      technical and cultural entity that is accessible to millions of persons outside
      the realm of government and academia. The field of medicine has been well served
      by this telecommunications system, in which many applications have been developed
      to assist in research, clinical medicine, and education. More recently, resources
      of specific interest to otolaryngologists have been implemented at various
      academic departments and national organizations. This review is intended to
      simplify the Internet for otolaryngologists who do not have extensive experience
      in computers or telecommunication. The Internet is described in basic, minimally
      technical terms, and specific examples are provided of ways that on-line
      resources can be used in the practice of otolaryngology-head and neck surgery.

PMID- 8758642
TI  - Malignant nerve sheath tumor of the nasal septum.

PMID- 8758643
TI  - Invasive aspergillosis of the larynx in AIDS.

PMID- 8758644
TI  - Obstructing laryngeal granuloma after brief endotracheal intubation in neonates.

PMID- 8758645
TI  - Massive, destructive, dentigerous cyst: A case report.

PMID- 8758646
TI  - Electrocautery burns and operator ignorance.

PMID- 8758647
TI  - Basal cell adenocarcinoma of the parotid gland.

PMID- 8758648
TI  - Benign cervical teratoma in the adult: report of a rare case with dense fibrosis
      involving adjacent vital structures.

PMID- 8758649
TI  - Adult acute epiglottitis caused by Serratia marcescens.

PMID- 8758650
TI  - Arytenoid dislocation.

PMID- 8758651
TI  - Nasal septal perforation and carotid cavernous aneurysm: unusual manifestations
      of systemic lupus erythematosus.

PMID- 8758652
TI  - Postlaryngectomy dysphagia caused by an anterior neopharyngeal diverticulum.

PMID- 8758653
TI  - Benign symmetric lipomatosis (Madelung's disease).

PMID- 8758654
TI  - Lymphangiomatous polyp of the palatine tonsil.

PMID- 8758655
TI  - Facial plastic surgery: subspecialty helps otolaryngology define its boundaries.

PMID- 8758656
TI  - Organ transplantation at the Hartford Transplant Center.
AB  - Over 1,243 organ transplants have been performed at the Hartford Transplant
      Center over the past two decades. Survival in kidney, heart, liver, and pancreas
      patients is at or above the national average. Hartford was one of the first
      centers to use triple immunosuppression, which significantly improved survival in
      kidney transplantation. For recipients of kidneys from living related donors and
      cadaveric kidneys, two-year actuarial graft survival has been 98% and 83%,
      respectively, over the last five years. For heart and liver transplants, two-year
      survival has been 79% and 67%, respectively. Despite high success rates at most
      transplant centers, donor organs remain scarce. This problem needs to be
      addressed through increased cooperative efforts in the health-care community and
      the general public.

PMID- 8758658
TI  - Minimum prostate-specific antigen (PSA) level diagnostic of prostate cancer.
AB  - The PSA levels in benign prostatic hyperplasia (BPH) and prostate adenocarcinoma
      (PA) overlap, both below and above 4 to 10 ng/mL. There is no known PSA level
      diagnostic of PA. In this study, data were obtained in 160 consecutive men aged
      58 to 87. Prebiopsy PSA levels (PSA-1) were obtained prior to "sextant" gun
      biopsies in 97 cases diagnosed as noncarcinoma, and in 56 cases diagnosed as PA.
      Multiple hematoxylin and eosin sections were made of each biopsy, and Gleason
      scores given the PAs. Cases were followed up to 30 months with repeated PSA
      levels and additional biopsies. The highest PSA level in NPA in this series was
      54.6 ng/mL.

PMID- 8758657
TI  - The current treatment of cervical disc rupture.

PMID- 8758659
TI  - The Internet: a new instrument in a virtual "doctor's bag".
AB  - The Internet is a valuable professional tool, and savvy physicians should
      understand its strengths and weaknesses. This worldwide network of networks
      allows doctors to communicate using any of several common Internet tools
      electronic mail, mailing lists, newsgroups, telnet, file transfer protocol,
      gopher, and the World Wide Web. Many sites on the World Wide Web are expressly
      designed for physicians, although users must be careful to evaluate information
      for accuracy and currency. In Connecticut, physicians can use CHIME-Net, which
      provides access to the Internet and easy exchange of financial and patient data.
      Physicians ready to plunge into the Internet should consult their hospital
      library or information services department for more information.

PMID- 8758661
TI  - Barbarism is part of human nature.

PMID- 8758660
TI  - Inadequate treatment of opioid dependence due to society's attitudes and beliefs.
AB  - The attitudes and beliefs held by society, including health professionals, are
      detrimental to the health and welfare of the chemically dependent. Dependency on
      psychoactive agents bears the hallmarks of a bona fide neurological illness due
      to alterations in neurons affected by exogenous neuroactive agents. Emphasis on
      abstinence as the only acceptable goal of treatment may be harmful to those
      incapable of attaining a drug-free state. Other alternatives for treatment must
      be offered without stigmatization and bias against the drug dependent. Methadone
      treatment for opioid dependence needs to be promoted and liberalized, especially
      because the oral route of administration eliminates the risks accompanying drug
      injection. Patients receiving methadone must be retained in treatment rather than
      terminated for rules infractions that are not harmful to others. This is an
      urgent matter in light of the current HIV epidemic among drug injectors.

PMID- 8758663
TI  - The century of the automobile: random reflections on technology.

PMID- 8758664
TI  - Subacute thyroiditis as fever of unknown origin.

PMID- 8758666
TI  - Extending the boundaries of medicine.

PMID- 8758667
TI  - Pressures: impact on health of adolescents.

PMID- 8758668
TI  - Strokes in children.

PMID- 8758669
TI  - Separation or synthesis: a holistic approach to therapeutics.

PMID- 8758670
TI  - Developmental learning disorders: clues to their diagnosis and management.

PMID- 8758671
TI  - Index of suspicion. Case 3. Diagnosis: Cushing syndrome.

PMID- 8758672
TI  - Rifampin.

PMID- 8758673
TI  - [Preoperative and postoperative chemotherapy of osteogenic sarcoma of the limbs
      in children].
AB  - BACKGROUND: A preoperative and postoperative chemotherapy regimen was applied to
      nonmetastatic osteosarcoma of the extremities in patients under 16 years of age
      to prevent the progress to metastatic disease and reduce the volume of the
      primary tumor in order to assess a conservative surgery. PATIENTS AND METHODS: A
      modified T-10 chemotherapy regimen was used before surgery, including high dose
      methotrexate, vincristine, bleomycin, cyclophosphamide and dactinomycin. After
      surgery patients with a grade of tumor necrosis > 90% received the same regimen
      up to 45 weeks of treatment. For the cases with necrosis < 90%, this regimen was
      substituted by adriamycin and cisplatinum. Survival was studied in relation with
      age, sex, tumor site, levels of alkaline phosphatase and LDH, surgical treatment
      and tumor necrosis in the surgical specimen after preoperative chemotherapy. Uni
      and multivariate analysis were performed. RESULTS: Twenty seven patients with
      ages ranging from 5 to 15 years (median 11 years) were treated. The most common
      site of primary tumor was femur, followed by humerus and tibia. In 9 cases (33%)
      tumor necrosis was > 90%. Consecutive surgery was performed in 20 patients and 7
      suffered amputation or disarticulation of the extremity. Twenty patients remain
      alive and disease-free at a median follow-up of 84 months. The probability of
      disease-free survival at 50 months is 71%. The only factor which influenced
      significantly the survival was the grade of tumor necrosis. Survival was 100% for
      the 9 patients with necrosis > 90% and 53% for the 18 cases with necrosis > 90%
      (p = 0.022). CONCLUSIONS: Preoperative and postoperative chemotherapy achieve
      disease-free survival in more than two thirds of patients with nonmetastatic
      osteosarcoma of the extremities and allow a non mutilating surgical treatment in
      the majority of them.

PMID- 8758674
TI  - [Effects of surfactant administration in premature infants with severe
      respiratory distress syndrome].
AB  - BACKGROUND: From January 1992 to June 1993 a study was performed to show whether
      the administration of surfactant to low birth weight infants with respiratory
      distress decreased the need for ventilatory support and improved survival.
      METHOD: Twenty three infants born at a single hospital received the surfactant
      (one dose of a 100 mg/kg divided in four aliquots) and they were eligible for the
      treatment if they met the following criteria: 1) Weight between 650 g and 2000 g;
      2) postnatal age 4 to 24 hours; 3) clinical-radiographic signs of respiratory
      distress, and 4) need of mechanical ventilation with FiO2 > or = 0.6. The results
      of the treatment were evaluated comparing the arterial-alveolar oxygenation
      ratio, maximal inspiratory pressure and the oxygenation index before and after
      the administration of surfactant. The last consecutive eighteen infants born at
      our hospital, before our study was started, that met the same criteria were
      elected as control group. RESULTS: In the group of infants treated with
      surfactant the arterial-alveolar oxygenation ratio increased from 0.10 +/- 0.009
      before treatment to 0.28 +/- 0.02 six hours after treatment (p < 0.01); the
      oxygenation index decreased from 37.79 +/- 4.27 to 12.71 +/- 1.17 (p < 0.01) and
      the maximal inspiratory pressure from 22.13 +/- 0.81 cmH2O to 19.52 +/- 0.76 (p <
      0.001) in the same period of time. This improvement was maintained during the
      following 72 hours. In the group of infants treated with surfactant, mortality
      decreased (p < 0.01), the frequency of pneumothorax diminished (p < 0.001) and
      the frequency of pulmonary haemorrhage increased (p < 0.05). The ventilatory time
      was similar in both groups of infants but the global length of stay of the
      newborn that received surfactant was longer due to the fact that the non
      survivors of the control group died before the 72 hours of life. CONCLUSIONS:
      Treatment with surfactant improves the initial evolution of the respiratory
      distress syndrome of the newborn and decreases mortality.

PMID- 8758675
TI  - [Clinical, psychological and biological variables in a group of 108 adolescent
      patients with anorexia nervosa].
AB  - BACKGROUND: To assess the clinical and psychological characteristics, hormonal
      changes derived from malnutrition and the prognostic factors in an adolescent
      group of patients with anorexia nervosa. PATIENTS AND METHODS: In this
      retrospective study specific case-history medical record for this disorder was
      used first with the parents and later with the patients. Depression
      questionnaires (BDI or CDI) and eating disorders questionnaires (EAT and CIMEC)
      were also administered, and hormonal tests were carried out. RESULTS: 98 out of
      108 patients (90.7%) were females. Mean age was 15 years, 23 patients (21.1%)
      showed major depressive disorders or obsessive-compulsive disorders besides
      anorexia nervosa. The duration of the disorder was 12.0 +/- 9.0 months. The age
      at onset of the disorder was 15.1 +/- 1.5 (10-17 years), and the percentage of
      weight loss ranged between 15.53%. In relation to the hormonal findings the low
      levels of T3, insulin, somatomedin, prolactin, LH and 17 B estradiol were shown
      up. There were no differences between inpatients and outpatients in relation to
      the age of onset of the disorder onset, duration of the disorder, percentage of
      weight loss, psychological variables or applied hormonal findings. There were
      differences in relation to the used psychometric tests, which differentiated
      between patients with a good and bad outcome. CONCLUSIONS: Major depressive
      disorders and obsessive-compulsive disorders are the most frequent comorbid
      psychiatric disorders in the anorexia nervosa. The age at onset of the disorder,
      duration of the disorder, percentage of weight loss and hormonal changes do not
      seem to influence in outcome, whereas initial affective and eating symptomatology
      tend to predict disorder outcome.

PMID- 8758676
TI  - [Introduction to molecular biology of endometrial cancer].

PMID- 8758677
TI  - [Clinical-basic or basic-clinical research?].

PMID- 8758678
TI  - [Proposals of a quality model in health care].

PMID- 8758679
TI  - [The new vaccines and immunologic response (and II). The antigenic presentation.
      Adjuvants as inducers of inducer T-lymphocyte cell-mediated response].

PMID- 8758680
TI  - [Metastatic cardiac tamponade in a patient with papillary carcinoma of the
      thyroid].

PMID- 8758681
TI  - [Sepsis: a pending subject for the 21st century].

PMID- 8758682
TI  - [Hyper-IgM syndrome linked to X chromosome and hepatopathy: a frequent
      association].

PMID- 8758683
TI  - [The coherence between the frontal-parietal cortex and cardiac sympathetic nerve
      activity in cats].
AB  - Experiments were performed on 86 cats anesthetized with chloralose, paralyzed
      with gallamine triethiodide and ventilated artificially. Autospectral and
      coherence analysis revealed that the frontal-parietal cortex activity (EEG) and
      cardiac sympathetic nerve discharge (SND) were remarkably correlated in 33/44
      cats. SND lagged EEG by 50 +/- 20 ms with a cross-correlation value of 0.4 +/-
      0.1. Coherence value was 0.25 +/- 0.05, indicating a statistically significant
      relationship between the two signals. Midbrain transection at stereotaxic plane
      A3 preferentially decreased SND power at frequencies 3-4.2 Hz, accompanied by a
      fall in mean blood pressure (5.47 +/- 0.13 kPa). The coherence of SND to EEG was
      eliminated after decerebration. However, the total power in EEG was not
      significantly affected. The SND rhythm and blood pressure returned nearly to
      control level within 1 h after decerebration. The effects of midbrain transection
      were significantly attenuated by prior minor lesions of the lateral hypothalamus
      or medial thalamus. These results suggest that the forebrain is responsible
      significantly for a component of sympathetic tone in anesthetic cats. The
      integrity of diencephalon is required for the participation of forebrain in
      setting the level of basal SND. Reduction in SND following decerebration was due
      in part to interruption of the descending influence from diencephalon and brain
      stem sympathetic rhythm generators are involved in compensating for the loss of
      the forebrain dependent component of SND.

PMID- 8758684
TI  - [Effect of substance P on the somatic membrane of rat DRG neurons].
AB  - Intracellular recordings were performed on isolated rat DRG neurons to
      investigate the changes in the membrane potential in response to substance P and
      the involved ionic mechanisms. The resting membrane potential examined was -58.9
      +/- 8.2 mV (X +/- SE) (n = 81). The conduction velocities estimated were: 20.4 +/
      4.8 m/s (X +/- SE) ranging from 14.1 to 28.7 m/s (47/60) in type A(alpha beta)
      cell, 9.8 +/- 5.2 m/s (X +/- SE) ranging from 1.2 to 13.7 m/s (13/60 in type
      A(delta) and type C cell. In majority of the neurons bath application of SP (10(
      7) - 3 x 10(-4) mol/L) induced marked membrane potential depolarization (56/60).
      The membrane conductance increased 24.6% in average from control value of 2.72 x
      10(-8) S during SP-induced depolarization (n = 3). The reversal potential was
      between +40 - %50 mV (n = 3). When NaCl in BSS was substituted with choline
      chloride or containing TTX (10(-5) mol/L), the amplitude of SP-induced
      depolarization attenuated markedly but not incompletion eventually. When high (20
      mmol/L) and low (0 mmol/L) Ca2+ BSS was used, the amplitude of SP-induced
      depolarization increased and decreased respectively. However, when BSS containing
      10(-4) mol/L Cd2+ or 10(-2) mol/L TEA was used SP-induced depolarization was
      reduced. The above results indicate that SP-induced depolarization involves a
      rather multiple changes in ionic conductance.

PMID- 8758685
TI  - [Effects of AF64A on neurons containing both nitric oxide synthase and choline
      acetyltransferase in the rat septal complex].
AB  - Ethylcholine mustard aziridinium ion (AF64A), a neurotoxic choline analog, was
      injected (ICV) bilaterally (1.5 nmol/ventricle, n = 10) into male adult rats to
      induce a model of Alzheimer's disease (AD). One month later, using NADPH
      diaphorase (NADPH-d) histochemistry followed by choline acetyltransferase (ChAT)
      immunocytochemistry (PAP) on the coronal sections of the septal complex, double
      staining experiments were performed to assay the alterations of septal
      cholinergic neurons coexisted with nitric oxide synthase (NOS). Compared to
      controls, AF64A can significantly reduce the numbers of ChAT single labelled
      neurons and NADPH-d + ChAT double labelled neurons in the dorsal subgroup (29.5%
      and 26.7%, respectively, P < 0.01). Moreover, the dendrites of these neurons were
      damaged. While administration of AF64A resulted in a significant decrease in the
      number of ChAT single labelled neurons (35.2%, P < 0.01) in the intermediate
      subgroup (rostral extension of the nucleus/substantia innominata) NADPH-d + ChAT
      double labelled neurons were unchanged (P > 0.05). In the midline and the ventral
      subgroups, both of these two kinds of cholinergic neurons were not affected
      significantly by AF64A (P > 0.05). Furthermore, AF64A had no effect on NADPH
      diaphorase single labelled neurons in all subgroups of septal complex. These
      results indicate that: (1) the administration of AF64A has different effects on
      the cholinergic neurons with or without NOS in different subgroups of the septal
      complex, and the NADPH-d + ChAT double labelled neurons resist the neurotoxicity
      of AF64A; (2) in the intermediate subgroup, the cholinergic neurons containing
      NOS may have projections different from those without NOS.

PMID- 8758686
TI  - [Subtypes of glutamate receptor and their distribution in the somatic membrane of
      neurons freshly isolated from rat DRG].
AB  - The aim of the present study was to investigate the distribution and coexistence
      of glutamate (Glu) receptor subtypes in the isolated rat DRG neurons as
      identified by the recorded NMDA-, KA- or QA/AMPA-activated current using whole
      cell patch-clamp technique. Of the 37 identified neurons, 15 contain only a
      single subtype receptor, 13 with two kind subtype receptors, only 4 with all
      subtype receptors. With regard the frequency of occurrence of the three types of
      receptors, the NMDA, KA and QA/AMPA subtype were found present respectively in 26
      (70.3%), 7 (18.9%) and 21 (56.8%) of the recorded cells.

PMID- 8758687
TI  - [Influence of peripheral process branching in nerve of spinal ganglion on the
      primary afferent impulse].
AB  - In order to observe the electrical and morphological characteristics of neurons
      in toad spinal ganglion (SG) preparation, microelectrode filled with 0.75%
      horseradish peroxidase (HRP) was used both for intracellular recording and for
      intracellular labelling. Histological result showed that there were apparent
      branchings in peripheral process of A type cells. Intra-axonal recording of the
      discharges of dorsal root fiber could be evoked by simultaneous stimulation of
      two separate fine bundles in spinal nerve. The discharging event exhibited the
      patterns of interruption, default and addition. The above results suggest that
      the peripheral process branching might alter the array and frequency of primary
      sensory afferent input.

PMID- 8758688
TI  - [Endotoxin causes release of calcitonin gene-related peptide (CGRP) from the
      isolated mesenteric arterial bed in rat].
AB  - Our previous work has shown that CGRP is released into the circulation during
      endotoxin or hemorrhagic shock in animals and septic shock in patients. We have
      also identified the blood vessels as a major source of production of circulating
      CGRP in the endotoxic rat. In the present study we determined whether ETX could
      directly trigger release of CGRP from CGRP-containing perivascular nerves in
      isolated mesenteric arterial bed (MAB) of rat. The results showed that ETX caused
      time- and concentration (10-100 micrograms/ml) -dependent release of CGRP. ETX
      (50 micrograms/ml) is increased by 20 fold CGRP in perfusate 10-15 min after ETX.
      Characterization of CGRP in perfusates by reverse-phase HPLC showed one
      predominant peak which coeluted with synthetic rat CGRP. Pretreated MAB with
      capsaicin or ruthenium red inhibited ETX-induced release of CGRP by 90% and 65%
      respectively. ETX-induced CGRP release was decreased under Ca2+-free perfusion by
      80%. The data suggest that ETX directly trigger the release of CGRP from
      capsaicin-sensitive sensory nerve innervating blood vessels. The release of CGRP
      is dependent on extra-cellular Ca2+ and Ca2+-induced Ca2+ release from the
      intracellular Ca2+ store which is sensitive to ruthenium red.

PMID- 8758689
TI  - [Correlation between ability of learning-memory and synaptosomal free [Ca2+]i in
      mice of different age].
AB  - In the present investigation, the behavior of learning and memory of 1-month and
      6-month-old mice was studied by using Y-maze and one-trial passive avoidance
      response device. The synaptosomal free [Ca2+]i of four main brain regions
      (Hippocampus, Cerebral cortex, Cerebellum, Tectum of midbrain) of these mice were
      measured by fluorescent probe Ca2+ indicator Fura-2 and an AR-CM-MIC cation
      measurement system. The results showed that, in comparison with 1-month-old mice,
      the ability of discrimination learning and memory of 6-month-old ones were
      attenuated, and the synaptosomal free [Ca2+]i of hippocampus was increased.

PMID- 8758690
TI  - [Effects of oxygen free radicals on myocardial alpha 1-adrenoceptor and its
      subtypes in rat].
AB  - The effects of oxygen free radicals on myocardial alpha 1-adrenoceptor and its
      subtypes and beta-adrenoceptor were observed by the method of radioligand binding
      assay in rat. The experiments showed: (1) .OH and O??? reduced the Bmax of alpha
      1-adrenoceptors binding to 125IBE2254 by 55% and 36%, respectively. (2) The KI
      values of alpha 1-adrenoceptors were increased by .OH (by 171%), but not by O2-.
      (3) Both .OH and O2-. increased the ratio of alpha 1A vs alpha 1B subtypes. (4)
      beta-adrenoceptors were not changed by either .OH or O2-. (5) Oxygen free radical
      scavengers mannitol and superoxide dismutase were capable of preventing the
      changes of alpha 1-adrenoceptor and its subtypes induced by oxygen free radicals.
      The above results suggest that oxygen free radicals can reduce the number and
      affinity of myocardial alpha 1-adrenoceptors, of which the alpha 1B subtype is
      more accessible to the changes.

PMID- 8758691
TI  - [Effects of endothelin on the electrical activity of sino-atrial pacemaker cells
      of rabbit].
AB  - The effects of endothelin-1 (ET-1) on the electrophysiological activity of
      pacemaker cells of rabbit sino-atrial node were examined by using intracellular
      microelectrode technique. The results obtained were as follows: (1) With
      superfusion of ET-1 (1-30 nmol/l), the velocity of diastolic depolarization (VDD)
      of pacemaker cells was significantly decreased in a concentration dependent
      manner, resulting in a reduced rate of pacemaker firing (RPF). (2) The decreases
      in RPF and VDD induced by ET-1 could be virtually blocked by pretreatment with
      ET(A) receptor blocker BQ-123 (20 or 100 micrograms/L). It was strongly suggested
      that the electrophysiological effects of ET-1 on the pacemaker cells were
      mediated by the ET(A) receptor. (3) The negative chronotropic action of ET-1 on
      the pacemaker cells was totally abolished by pretreatment with a kind of KATP
      channel blocker glibenclamide (10 mumol/L). On the basis of above results, it
      appears that the binding of ET-1 with ET(A) receptor may induce an activation of
      KATP channels with resultant increase in K+ current so as to decrease the
      velocity of diastolic depolarization in the pacemaker cells.

PMID- 8758692
TI  - [Projections from pontine pneumotaxic center to medullary Botzinger complex in
      cats].
AB  - Experiments were done on 33 adults cats. After injection of WGA-HRP (5%, 30-60
      nl) into the Botzinger complex, labelled cells were observed in the lateral
      parabrachial nucleus and the Kolliker-Fuse nucleus. Injection into control sites
      failed to label the cells in the above two nuclei. Ninety-one respiratory related
      neurons recorded from the pneumotaxic center were tested by electrical
      stimulation of the Botzinger complex. Thirteen neurons (14.3%, inspiratory 11,
      phase-spanning 2) could be antidromically activated. Results of the present study
      showed that neurons in the pneumotaxic center sent axons to the Botzinger complex
      concerning respiratory control.

PMID- 8758694
TI  - [Capsaicin-sensitive afferent neurons and endogenous nitric oxide (NO) mediate
      the gastric acid secretion and hyperemic responses to intragastric peptone].
AB  - Using hydrogen gas clearance technique to measure gastric mucosal blood flow
      (GMBF) and a high dose of capsaicin to ablate the capsaicin-sensitive afferent
      neurons, the role of capsaicin-sensitive neurons in the gastric acid secretion
      and hyperemic response to intragastric peptone was investigated. The results were
      as follows: (1) there was an increase in acid secretion associated with the
      hyperemic response to intragastric peptone; (2) pretreatment with a high dose of
      capsaicin to ablate afferent neurons completely abolished the gastric hyperemic
      response to intragastric peptone and partially inhibited the acid secretion; (3)
      the gastric hyperemic response to intragastric peptone was completely blocked by
      pretreatment with L-nitro-arginine methyl ester (L-NAME), whereas the acid
      secretion was significantly attenuated; (4) inhibited effects of L-NAME on acid
      secretion and GMBF could be reversed by pretreatment with L-arginine (L-ARG); (5)
      pretreatment with atropine inhibited gastric acid output (GAO) and partially
      attenuated GMBF. These results suggested that capsaicin-sensitive afferent
      neurons and endogenous NO were involved in the gastric acid secretion and
      hyperemic response to intragastric peptone and the hyperemic response was
      mediated by both cholinergic and noncholinergic neurons.

PMID- 8758693
TI  - [Expression of c-fos mRNA induced by pressure overload in the left ventricle].
AB  - In the present study the effect of pressure overload on the expression of
      protooncogene c-fos in the left ventricle was investigated in rats with abdominal
      aorta constriction. It was found that a remarkable expression of c-fos was
      induced by pressure overload and the expression was greatly attenuated by
      angiotensin converting enzyme inhibitor captopril. In the pressure overload group
      the angiotensinogen mRNA level was found increased. The above results suggest
      that angiotensin II is involved in the expression of c-fos due to pressure
      overload.

PMID- 8758695
TI  - [Effect of neuromedin C on gastrin secretion from isolated and perfused rat
      stomach].
AB  - Using a model of isolated and perfused rat stomach, it was observed that the
      gastrin secretion was increased significantly by intravascular perfusion of 10(
      8) mol/l neuromedin C (NMC) (from 550 +/- 126 pg/10 min to 1060 +/- 180 pg/10
      min, P < 0.01). The effect was in part suppressed by atropine (10(-7) mol/L) (756
      +/- 152 pg/10 min v.s. 1060 +/- 180 pg/10 min, P < 0.05) and completely blocked
      by D-Phe6-BN (6-13) OMe (10(-6) mol/L), a bombesin receptor antagonist from human
      antral G-cells. These results indicate that NMC is a powerful stimulant for
      gastrin secretion mostly by directly stimulating G-cells and, to some extent, by
      stimulating cholinergic pathway. It was also suggested that the bombesin-related
      receptor in rat stomach is similar to that in the human G-cells.

PMID- 8758696
TI  - [Effect of L-TYR on the uterine cytosol estradiol and progesterone receptors in
      rat].
AB  - The effect of L-TYR on rat uterine cytosol estradiol and progesterone receptor
      contents was studied. The rats were divided into 4 groups: proestrus, estrus,
      metestrus and diestrus. One horn of each uterus was injected with L-TYR (2
      mmol/L, 0.1 ml), while the other with 0.1 ml 0.9% NaCl serving as control. The
      mole concentration of receptor was calculated with RRA and cytosol receptor
      content was expressed as fmol/mg protein. It was shown that L-TYR decreased
      significantly the uterine estradiol and progesterone receptors in proestrus,
      estrus and diestrus phases of the estrus cycle, but without effect on metestrus.
      This was most probably due to competitive combination of TYR with some functional
      groups of the estradiol receptor because of similar chemical conformation of TYR
      to estradiol. Threonine could also decrease, to some extent, the uterine cytosol
      progesterone receptor content at estrus and dioestrus phases. Serine had no
      effect on the contents of uterine cytosol either estradiol or progesterone
      receptor in normal and ovariectomized rats. The present observation indicates
      that L-TYR appears to affect the synthesis of the cytosol estradiol and
      progesterone receptor in the rat uterus independent, however, of endogenous
      ovarian sex hormones, since the effect is still present in the ovariectomized
      animals.

PMID- 8758697
TI  - [Frequency dependence of substance P release by electroacupuncture in rat spinal
      cord].
AB  - Previous studies in our laboratory have shown that electroacupuncture (EA) using
      different frequencies produced differential opioid peptides release in the spinal
      cord of rats and human beings. In the present study we observed the frequency
      dependence of substance P (SP) release from rat spinal cord, with the frequencies
      of EA set at 2, 4, 8, 15, 30 and 100 Hz. The spinal perfusate was collected in 3
      periods of 30 min before, during and after EA, and the immunoreactive SP (SP-ir)
      was measured by radioimmunoassay (RIA). The effectiveness of EA-induced analgesia
      was assessed by tail flick latency (TFL). Rats showing an increase of TFL over
      40% was considered as EA responder. The results showed that in the responders, SP
      ir in spinal perfusate showed a moderate decrease during 2 Hz EA, (P < 0.01
      compared with baseline level), no change in the 4 Hz EA group, and a marked
      increase during 8, 15, 30 and 100 Hz EA (P < 0.01), with maximal increase
      occurring at 15 Hz (P < 0.001). The above results suggest that EA may induce
      upward or downward modulation in SP-ir release depending on the frequency of EA.
      However in the non-responder rats no change in spinal fluid SP-ir content was
      observed. This suggests that changes in SP-ir release have same causal relation
      with the analgesia induced by EA stimulation.

PMID- 8758698
TI  - [Solubilization of beta-bungarotoxin-binding protein from rat diaphragm and
      inhibition of its binding by some other presynaptic neurotoxins].
AB  - The mechanism of the transmitter release-blocking action of beta-bungarotoxin at
      neuromuscular junctions is probably related to the binding of the toxin to a
      presynaptic voltage-dependent K+ channel. In this paper we report the
      solubilization of beta-bungarotoxin-binding protein from rat diaphragm membrane
      preparations with Triton X-100. The specific binding activities of the detergent
      extracts are 200-400 fmol/mg of protein, and the yields are about 50%-70%. The
      binding of 125I-beta-bungarotoxin to the extracts could be completely inhibited
      by dendrotoxin, with an IC50 of about 8 x 10(-8) mol.L. Another beta-neurotoxin,
      beta-agkistrodotoxin, however, could not inhibit the 125I-beta-bungarotoxin
      binding at all. This indicates that the acting sites of beta-agkistrodotoxin on
      the presynaptic membranes are different from those of beta-bungarotoxin.

PMID- 8758699
TI  - [Effect of hedgehog hydnum on the delay of fatigue in mice].
AB  - Two groups of mice were fed with either hedgehog hydnum powder or extract for
      sixty days. For the assay of fatigue, the activity of serum lactate
      dehydrogenase, the serum urea nitrogen content, blood lactic acid, hepatic and
      muscular glycogen, and the physical stamina of the mice were determined. The
      activity of serum lactate dehydrogenase and the hepatic and muscular glycogen
      content in the experimental mice were evidently higher than that in the control
      mice (P < 0.05 or P < 0.01). After exercise, the increase in blood lactic acid
      and serum urea nitrogen in the experimental mice was significantly lower than
      that in the control mice (P < 0.05 or P < 0.01), but the rate of elimination of
      blood lactic acid in the experimental mice was significantly higher than that in
      the control mice (P < 0.05). In the physical stamina swimming, the experimental
      mice drowned after a longer period of time than the control mice (P < 0.05). In
      conclusion hedgehog hydnum had a significant effect on raising physical stamina
      and delaying fatigue in mice.

PMID- 8758700
TI  - Clinical investigation of traditional Chinese medicine and pharmacy in treating
      respiratory tract infections in AIDS.
AB  - Based on the difference in severity of the disease and complications, 80 cases of
      acquired immune-deficiency syndrome (AIDS) accompanied with cough were divided
      into 2 groups: One treated by traditional Chinese medicine (TCM group), including
      58 cases and the other treated by Integrated Chinese and Western medicine
      (integrated group), 22 cases. The therapeutic results show that in the TCM group
      there were 18 cases (31.03%) with clinical cure of the respiratory tract
      infection, 7 cases with therapeutic effect (12.07%) and 33 cases without any
      effect (56.90%), for a total rate of 43.10% therapeutic effectiveness; while in
      the integrated group there were 6 cases with clinical cure (27.27%), 2 cases with
      therapeutic effect (9.09%) and 14 cases without any effect (63.64%), the total
      rate of therapeutic effectiveness being 36.36%, slightly lower than in the TCM
      group and possibly related to greater severity of the disease or complications.

PMID- 8758702
TI  - 62 cases of chronic prostatitis treated by rectal ionintroduction of TCM
      suppository.

PMID- 8758701
TI  - Research into analgesia by inhaling analgesic.
AB  - This article deals with analgesia by inhaling analgesic. According to Chinese
      medical theories, TCM analgesics were chosen from the literature and folk
      prescriptions screened and proved by analgesic tests on animals. A reasonable
      prescription was made up and the drug inhaled. Its analgesic effect was superior
      to that of dolantin injection (3 mg/kg body weight, intraperitoneal injection).
      Clinical trials showed its analgesic effect in 3-10 minutes and it lasted for
      more than 2 hours in over 70% of the cases for a total effective rate of 94.6%.
      The drug is absorbed quickly and acts directly on the nerve center. Its use is
      not addictive.

PMID- 8758703
TI  - Observation of curative effect of acupuncture therapy plus scalp acupuncture for
      restoring consciousness and inducing resuscitation in 80 cases of acute apoplexy.
AB  - During our 4-year work in The Republic of Yemen, the authors used acupuncture
      therapy to restore consciousness and induce resuscitation plus scalp acupuncture
      in 80 cases of acute apoplexy, with 63 cases cured, accounting for 78.75%. This
      therapy is obviously superior to the traditional principle of point selection in
      acupuncture used in 25 cases as to curative effect, treatment course and other
      aspects. There is an obvious statistical difference (P < 0.005).

PMID- 8758704
TI  - Clinical experience of Dr. Shao Jingming in treatment of diseases by puncturing
      back-shu points.

PMID- 8758705
TI  - Clinical observation on Hashimoto's thyroiditis treated by indirect moxibustion
      with various Chinese medicines.

PMID- 8758706
TI  - Ear point tapping and pressing therapy for giving up smoking in 45 cases.

PMID- 8758707
TI  - 206 cases of spinogenic dizziness treated by contralateral acupuncture.

PMID- 8758708
TI  - 3-directional penetration needling for the treatment of paralysis.

PMID- 8758709
TI  - TCM treatment in three cases of splenic hypofunction with water retention.

PMID- 8758710
TI  - Manuduction of adhesive ankylosis of the knee under anesthesia.
AB  - This paper reports 60 cases of adhesive ankylosis of the knee treated by
      manuduction under anesthesia. Excellent and good effects were achieved in 50
      cases (83%), and normal function of the knee joint was maintained in 35 of the 40
      cases followed up for more than one year.

PMID- 8758711
TI  - Studies of Qingyangshen (II): modulatory effect of co-treatment with qingyangshen
      and diphenylhydantoin sodium on rat hippocampal c-fos expression during seizures.
AB  - We have reported that, after KA treatment in rats, there was first a significant
      increase in hippocampal c-fos expression during acute seizures and then a long
      term inhibition in hippocampal c-fos expression during chronic seizures. In this
      experiment, we examined the modulatory effect of Qingyangshen (QYS), a
      traditional Chinese medicine with antiepileptic property, and diphenylhydantoin
      sodium (DPH) on hippocampal c-fos expression during seizures. We found that after
      intraperitoneal injection of QYS + DPH (15 mg/kg and 50 mg/kg respectively,
      q.o.d. x 6), the peak level of hippocampal c-fos mRNA induction during KA-induced
      acute seizures was reduced by 56.27%; while the inhibition of hippocampal c-fos
      expression during KA-induced chronic seizures was disinhibited to control level.
      It is suggested that the inhibitory effect of QYS + DPH on KA-induced seizures,
      chronic seizures in particular, may have much to do with its modulatory effect on
      hippocampal c-fos expression.

PMID- 8758712
TI  - Effect of herba artemisiae scopariae on cytogenetic damage induced by aflatoxin
      B1.
AB  - It was found that the per mill rate of micronucleus of marrow cells in mice
      induced by AFB1 decreased with the increasing dosage of Herba Artemisiae
      Scopariae, and that there were dosage-effect relations in the lowering of
      percentage of chromosomal aberration induced by AFB1 and in the inhibition effect
      on some sister chromatid exchanges per cell.

PMID- 8758713
TI  - Progress of experimental studies on prescriptions designed by Zhang Zhongjing.

PMID- 8758714
TI  - Advanced in studies on acupuncture abstinence.

PMID- 8758715
TI  - Indications and contraindications in emergency acupuncture treatment.
AB  - This essay suggests the indications and relative contraindications in the
      emergency treatment and cure by acupuncture and moxibustion based on an analysis
      of the characteristics and principles of treatment in emergency cases and the
      many-sided regulating effects of acupuncture and moxibustion. It also introduces,
      case by case, methods of acupuncture and moxibustion treatment in 22 frequently
      encountered emergency situations, and stresses the fact that emergency treatment
      with acupuncture and moxibustion must be based on the various new achievement and
      experience and strictly observe rules of operation. It states that only by doing
      so can the therapeutic effect be enhanced and adverse reactions prevented.

PMID- 8758716
TI  - [Experimental study on "three-dimensional" culture of scar-derived fibroblasts].
AB  - Based on the monolayer cell culture system, we resuspended the scar-derived
      fibroblasts in a solution of polymerizing collagen to develop a "three
      dimensional" cell culture system. In this system, cells, extracellular matrices
      and various modulating factors were associated to form an organic entity, in
      which the fibroblasts express their biologic characteristics similar to that in
      living body. With the three-dimensional system, we could study not only the
      morphology, proliferation and metabolism of fibroblasts, but also their
      cytophysiology, such as the role on connective tissue contraction. We recommend
      this culture system as a better model in the research of wound healing and scar
      formation.

PMID- 8758717
TI  - [The effects of retinoic acid on the ultrastructure of cultured fibroblasts].
AB  - The paper reports the effects of retinoic acid on the ultrastructure of cultured
      fibroblasts. Electron microscopic observation (SEM and TEM) showed that fibrous
      substances on the cell surface and outside the cell had decreased. The results
      indicated that retinoic acid inhibits collagen synthesis of fibroblasts. The
      possible mechanism of the effect of retinoic acid in the treatment of scar is
      discussed.

PMID- 8758718
TI  - [A study of human keloid with electron spin resonance].
AB  - Electron spin resonance (ESR) was used to examine human keloid, normal connective
      tissue and skin. The results showed that more oxygen free radicals were
      identified in keloid, less in normal connective tissue while no free radicals
      were found in skin. The author discussed the significance of the occurrence of
      oxygen free radicals and its relation with keloid and suggested that reduction or
      elimination of production of oxygen free radicals by its scavenger may be of help
      in preventing the excessive growth of scar tissue.

PMID- 8758719
TI  - [Regeneration of free nerve endings and sensory corpuscles after implantation of
      nerve into the denervated skin in the monkey].
AB  - Two rhesus monkeys were used. Their fingers were denervated first and then the
      nerve was implanted into the denervated skin. The results showed that: (1) the
      process of regeneration of nerve fibers was similar to that of previous
      experiments in rabbits; (2) regeneration of nervous tissue included 2 kinds of
      sensory receptors with capsule-Meissner corpuscles and Merkel cell-dendrite
      complex; (3) the regenerative rate of Meissner corpuscles increased progressively
      and their morphology and structure became matured with elapse of time; (4) no
      regeneration of pacinian corpuscle was found in 6 months after nerve
      implantation; (5) Meissner corpuscles also regenerated in the transplanted
      glabrous skin.

PMID- 8758720
TI  - [Experimental study on antibacterial activity of subdermal vascular network
      island skin flap].
AB  - A comparison study was carried out on the antibacterial activity between two
      kinds of pig buttock flaps: the conventional island skin flap and the subdermal
      vascular network island skin flap which was created by thinning the distal half
      of a conventional island flap, preserving its subdermal vascular network.
      Antibacterial activity was evaluated by bacterial counts, phagocytic index and
      intracellular bacterial killing ratio of leukocytes, skin temperature, laser
      Doppler, ink perfusion, microangiography and transparent specimen technique. The
      results indicated that antibacterial activity of the subdermal vascular network
      island skin flap was much lower than that of the conventional island skin flap.
      The reduced blood supply and decreased leukocyte function were responsible for
      the low antibacterial activity after the conventional island flap was thinned.

PMID- 8758721
TI  - [One-stage repair of hypospadias with double-pedicle scrotum septal flap].
AB  - Nine cases of hypospadias were repaired using double-pedicle scrotum septal flap
      from December 1991 to December 1992. Success was achieved in all cases. The key
      point of success was to preserve the vascular pedicle to the flap. The operative
      technique and the management of complications are described.

PMID- 8758722
TI  - [Sternocleidomastoid muscle lengthening for the cure of muscular torticollis].
AB  - A Z-plasty was designed to lengthen the sternocleidomastoid muscle for the
      treatment of muscular torticollis. Since September 1990, forty-nine patients (36
      males, 13 females) have been treated. Their age ranged from 2 to 22 years old.
      Follow-up of there months to three years showed 95.9% of them were good results.
      The paper not only described the operative procedure, indications, choice of
      anaesthesia. postoperative functional exercise and the application of neck
      splint, but also emphasized the aesthetic effect to the operation.

PMID- 8758723
TI  - [Eyebrow reconstruction by a scalp island flap based on the frontal branch of the
      superficial temporal artery].
AB  - The author studied the course and measured the length of the frontal branch of
      the superficial temporal artery in 30 normal subjects. 19 eyebrows were
      reconstructed in 11 burned patients using the scalp island flap based on the
      frontal branch of the superficial temporal artery. The results were satisfactory.
      The reconstructed eyebrows looked natural with wooly hair of the frontal
      hairline. This method can be used not only in male patients but also in female or
      pediatric patients.

PMID- 8758724
TI  - [Evaluation of levator palpebrae superioris muscle resection in 500 cases].
AB  - We sum up the effects of levator palpebrae superioris muscle resection to correct
      congenital ptosis in 500 cases. The surgical results in 369 cases (73.8%) are
      excellent; ninety-six cases (19.2%) are good and 35 cases (7%) are poor. The
      operative result depends on the amount of muscle resection. We believe that the
      levator palpebrae superioris muscle resection is the first choice of treatment
      for a patient whose levator has no function. The operation method is described
      and the indications of the operation and related problems are discussed.

PMID- 8758725
TI  - [Clinical application of medial leg skin flap for the repair of defects of the
      extremities].
AB  - A total of fifteen medial leg skin flaps with the posterior tibial artery as an
      axial vessel have been applied successfully to reconstruct extremity defects,
      such as chronic ulcers, scar contracture, high-voltage electric injuries and hot
      crush, etc. This skin flap can be elevated as a free flap, or vascular island
      flap, or cross-leg vascular pedicle flap to resurface the defects on the
      extremities. It is especially suitable for foot repair because of its long
      vascular pedicle and wide rotational arc as an island skin flap. The paper
      describes and discusses the indications, design and operating technique of this
      flap.

PMID- 8758726
TI  - [Clinical application of intraoperative sustained limited expansion].
AB  - Since May 1993, the technique of intraoperative sustained limited expansion
      (ISLE) had been applied clinically in 21 cases for the immediate reconstruction
      of soft tissue defects. Satisfactory results were obtained in 18 cases (85.7%),
      and failed in 3 cases (14.3%). ISLE had been applied successfully in various
      regions of the body. It had been shown that the results were dependent on the
      extent of soft tissue defect, the extent of intraoperative tissue gain, and the
      time of intraoperative sustained expansion.

PMID- 8758727
TI  - [Influences of early enteral feeding enriched with glutamine on the gut blood
      flow and oxygen consumption in severely burned mini-swines].
AB  - In order to investigate the effects of L-glutamine on the gut blood flow and
      oxygen consumption after burn, 14 mini-swines were randomly and equally divided
      into Non-Gln group and Gln group (which was supplied with L-glutamine, 0.64 g/kg
      day). Gut blood flow and oxygen consumption were continuously determined from
      preburn to PBD 10. The results showed that portal venous blood flow (Fpv) and
      oxygen consumption decreased markedly in all animals, especially the Non-Gln
      group (P < 0.01), on PBD 4 to PBD 10, when Fpv and oxygen consumption returned to
      preburn level in Gln group and remained low in Non-Gln group. The portal venous
      MDA concentration was significantly higher in Non-Gln group than that of Gln
      group. The results suggest that early enteral feeding enriched with glutamine
      increases the intestinal blood flow, and decreases the intestinal hypoxemia and
      reperfusion injury.

PMID- 8758728
TI  - [Relationship between disturbances of microcirculation and TNF during burn
      shock].
AB  - The changes in microcirculation and the level of plasma TNF in rat at the early
      stage of burn shock were measured, and the effects of Polygonum cuspidatum (PC)
      on above mentioned changes were observed. It was shown when the level of plasma
      TNF was increased, the number of adhesive leukocytes on venule wall was increased
      and the number of open capillaries were reduced significantly, and there were
      apparent aggregation of leukocytes and injury in lungs. The level of plasma TNF
      and the number of adhesive leukocytes were nearly normal, and the degree of
      aggregation of leukocytes and injury of lungs were attenuated by giving PC. The
      present study showed that the level of elevated plasma TNF in the early stage of
      burn shock was directly correlated with the adherence of leukocytes and the
      closing of capillaries. The administration of PC could apparently inhibit the
      increase of leukocytes, and at the meantime, attenuate the adherence of the
      neutrophils and injury of the lung. The results confirmed that the elevation of
      plasma TNF might be involved in the development of adherence of neutrophils and
      the disturbances of microcirculation in burn shock.

PMID- 8758729
TI  - [Relationship between wound healing and TNF, MDA and SOD contents in granulation
      tissues of rats in the first week].
AB  - An experimental model was used to determine the changes in TNF, MDA and SOD in
      granulation tissues during natural wound healing after skin excision on rats. Our
      results indicated that the changes in TNF and SOD exhibited a curve of V. The
      levels of TNF and SOD were lower on day 7 than day 3. The levels of MDA rose
      gradually, especially on day 7. A positive correlation was shown between TNF and
      MDA (at days 3, 5, 7), also between TNF and SOD (at day 3, 7). When the
      concentration of TNF was lower than 90 Pg/mg protein, the process of wound
      healing was best, while wound healing was hindered when the levels of SOD were
      low. The results suggest that in the process of wound repair there are
      influential changes in the contents of TNF, MDA and SOD. Lower levels of TNF and
      higher levels of SOD are apparently beneficial to wound healing after trauma.

PMID- 8758730
TI  - [The dynamic change in the levels of hydroxyproline in the burned wound].
AB  - Hydroxyproline, the main component of collagen, and morphological changes were
      assayed dynamically in the superficial second-degree burn wounds of rats, with
      the aim to investigate the change in collagen and its relationship with
      epidermization of burn wound. The results are as follows. Epidermal layer was
      lacking and higher levels of OHP were noted in the early days postburn, OHP
      peaked on the 3rd day, declined to normal on day 10 and day 14 postburn, the
      latter event was in pace with the epidermization of the burn wound. These results
      indicated that the levels of collagen in the superficial second-degree burn wound
      were mainly regulated by epidermal cells. Epidermization might inhibit over
      proliferation of collagen. Epidermal derived factor (EDF) might be the main
      factor regulating the synthesis of collagen in the superficial second-degree burn
      wound.

PMID- 8758731
TI  - [Immune and biochemical analysis of protein of homogenates of three different
      kinds of skin].
AB  - The amount and constitution of protein, its ultraviolet photo-absorption ability,
      and esterase in homogenates of human cadaveric and guinea pig skin (each
      consisted of newborn, fresh adult and stored adult skin) were assayed by using
      ultraviolet spectrophotometer, polyacrylamide gel electrophoresis and sodium
      dodecyl sulphate polyacrylamide gel electrophoresis. Our experiment shows that
      immune and biochemical analysis of protein of three different skin groups are
      different. The biochemical components of cadaveric and guinea pig skin protein
      and esterase in newborn skin group are lowest. The changes in adult skin stored
      at -196 degrees C are less obvious as compared with that in fresh adult skin.

PMID- 8758732
TI  - [Changes in blood gas in burned patients in Xining].
AB  - The changes in arterial blood gas were observed and analysed in twenty-seven
      burned patients at high altitude. It was showed that a serious hypoxemia existed
      in burn patients, both in survivors and dead cases, and that hypoxemia occurred
      earlier in the cases with inhalation injury or dead cases than without inhalation
      injury. These results suggest that patients with inhalation injury should undergo
      tracheostomy as early as possible to ensure oxygen supply, and patients without
      inhalation injury should be give oxygen therapy routinely. ARDS occurred in all
      inhalation injury cases, and high frequency jet ventilation was effective in
      improving hypoxemia in such cases.

PMID- 8758733
TI  - [Dynamic study of renal function with radioimmunoassay technique (RIA) in burn
      patients].
AB  - Alb, beta 2-m, IgG in serum and urine were determined in 52 burn patients (from
      January 1993 to December 1994) with RIA technique. The results revealed that
      there was no obvious connection between the area of burn and the alteration in
      these parameters (P > 0.05). Our findings indicated a positive correlation
      between the depth of burn and impairment in the renal function. The recovery of
      renal function was gradual, and that of glomerulus was earlier than renal
      tubules. Monitoring of renal function with RIA technique showed a higher
      sensitivity and accuracy than routine examinations, and it might play an
      important role in the treatment of burned patients in different periods.

PMID- 8758734
TI  - [Endotoxemia and carbonhydrate metabolism].

PMID- 8758735
TI  - The relationship between mast cell infiltration and the expression of PCNA and
      EGFr in experimental hepatocellular carcinoma of liver and squamous cell
      carcinoma of stomach in rats.
AB  - The expression of PCNA and EGFr in chemically induced hepatocellular carcinoma of
      liver and squamous cell carcinoma of stomach in rats were immunohistochemically
      observed. The results showed that the carcinoma cells of both tumors revealed a
      positive immunreaction to PCNA and EGFr. The histochemical observation of mast
      cell (MC) in both tumor tissues showed that the amount of MC in the surroundings
      of tumor cell nests was markedly different. According to the amount of the
      surrounding MCs the tumor cell nests could be divided into two groups: Group A
      with abundant MC infiltration and Group B with only scarce or without MC
      infiltration. The PCNA-positive cells in the tumor cell nests of both groups were
      calculated respectively. The results revealed that the amount of PCNA-positive
      cells in the group B was markedly more than that in the group A. The numerical
      ratio between two groups was 3:1 in the liver carcinoma and 2:1 in the stomach
      carcinoma approximately. An overexpression of EGFr was observed in tumor tissues
      of both groups, but there was also a marked difference in the amount of
      positively expressed cells and in the intensity of their staining reaction
      between both groups. The positively expressed cells in group B were much more and
      their staining intensity was much stronger than those in group A. According to
      the above mentioned results of observation, the expression state of both factors
      (PCNA and EGFr) was basically identical, suggesting that the MC may possess some
      inhibitory effect upon the growth rate of tumor cells of the experimental
      hepatocellular carcinoma of liver and the squamous cell carcinoma of stomach in
      rats.

PMID- 8758736
TI  - [Study of an ancient corpse of the Warring States period unearthed from Tomb No.
      1 at Guo-Jia Gang in Jingmen City (A comprehensive study)].
AB  - An ancient female corpse excavated from the robbed tomb No. 1 at Guo-Jia-Gang in
      Jingmen city of Hubei Province was studied. It was confirmed that the corpse was
      buried more than 2,300 years ago, namely at the middle stage of the Warring
      States period and is the earliest one of the ancient coffin corpses unearthed in
      China so far. It is of the same type as the ancient corpses of Weatern Han
      Dynasty excavated from tomb No. 1 at Ma-Wang-Dui in Changsha City and from the
      tomb No. 168 at Phoenix Hill in Jinagling City respectively. The collagenous
      fibers of connective tissue from all parts in the corpse were well preserved,
      showing fine ultrastructure with clear periodical cross banding, and a lot of
      bacterial spores were found between them. In addition, a large number of eggs of
      clonorchis sinensis and trichuris trichiura were found in the content of the
      bowel. The level and the cause of good preservation were discussed and it was
      believed that the good preservation may result from the combined effect of the
      internal and external environmental factors around the corpse.

PMID- 8758737
TI  - Construction of eukaryotic expression vector pBlacz and its expression both in
      vitro and in vivo.
AB  - A novel eukaryotic expression vector pBlacZ was constructed, which was
      transfected into the cell lines of NIH/3T3, COS-1, CHO and the primary culture of
      murine dermatic fibroblasts in vitro, and also into the murine subcutaneous layer
      and skeletal muscles of rats in vivo. It was detected that the gene expression
      vector could encode the E. Coli beta-galactosidase effectively in all these
      histocytes. The results suggested that pBlacZ, as a novel expression vector,
      might have certain value of application.

PMID- 8758738
TI  - The effects of radiofrequency catheter ablation on the metabolic enzymes and
      Ca(++)-ATPase of myocytes.
AB  - Using histochemical technique, the effects of radiofrequency catheter ablation
      (RFCA) on the activities of LDH, SDH, CCO, and Ca++-ATPase of guinea-pig
      ventricular myocytes were examined. The histological changes were observed for
      comparison. Radiofrequency energy (500 kHz) delivered was 20 W x 10 s. The
      results were as follows: RFCA resulted in significant impairments in all the four
      kinds of enzymes but without statistical differences in the areas involved in
      this energy level. No statistically significant difference was found between the
      ranges of enzymatic damages and areas of pathological lesions. These findings
      showed a consistency in areas of the histological and histochemical lesions
      resulted from RFCA.

PMID- 8758739
TI  - ALP induction by beta-glycerophosphate during the non-mineralization phase in
      vitro.
AB  - beta-GP influences on rat osteoblast development at the early period of culture
      i.e., the non-mineralization phase, and changes with the different cell passages
      were investigated. Alkaline phosphatase (ALP) was chosen as a main object.
      Northern blot analysis revealed up to two-fold increase in the steady state level
      of ALP mRNA after stimulation of rat osteoblast with 10 mM beta-GP. Likewise, 10
      mM beta-GP induced a 10-30% increase in ALP activity (P < 0.01) of early passages
      (1 to 4), but not of later passages (5 to 6). The beta-GP induced increase in ALP
      activity was totally inhibited by the protein synthesis inhibitor, cycloheximide
      (50 microM). beta-GP stimulation was found to be without effect on cell
      proliferation measured as 3H-thymidine incorporation. It is concluded that beta
      GP has no effect on proliferation but induces an increase in both mRNA level and
      activity of ALP in the non-mineralization phase of cultures of fetal rat
      calvarial cells, which lasts for several passages but will disappear in older
      cultures.

PMID- 8758740
TI  - [Detection and significance of HCV RNA in saliva, seminal fluid and vaginal
      discharge in patients with hepatitis C].
AB  - To investigate the transmission of HCV infection through family contact, we
      detected HCV RNS in body fluids (saliva, seminal and vaginal discharge) of 16
      serum HCV RNA positive patients (including 7 men and 9 women) and in sera of
      their family members. The positive rates of HCV RNA in the body fluids were
      31.25% (5/16) in saliva, 57.14% (4/17) in seminal fluid and 22.22% (2/9) in
      vaginal discharge, respectively. Among the family members in our series, all were
      negative for both anti-HCV and HCV RNA, despite two spouses positive for HCV RNA.
      This result strongly suggested the potential possibility of the transmission of
      HCV infection through the family contact.

PMID- 8758741
TI  - Application of Fuzzy mathematics to the evaluation of drinking water quality in
      Wuhan.
AB  - The quality of raw water from major water plants in Wuhan was evaluated by using
      Fuzzy synthetic evaluation model. It is suggested to select the alternative
      synthetic evaluation model when the first Fuzzy synthetic model failed in order
      to increase accuracy.

PMID- 8758742
TI  - Effects of nerve growth factor on axonal retrograde transport after axonal injury
      of motoneurons.
AB  - In this experimental study we coupled nerve growth factor (NGF) with notatin by
      dicyclohexylcarbodiimide to label NGF and observed the effects of NGF on axonal
      retrograde transport after axonal injury of motoneurons with the aid of notatin
      chemiluminescence system. The results showed that NGF could be transported
      through axon not only to sensory neurons in dorsal root ganglia but also to
      motoneurons in spinal cord ventral horn.

PMID- 8758743
TI  - Portal hypertensive vascular lesions.
AB  - The aim of present study is to assess the pathological changes of gastric
      coronary vein in cirrhotic patients (n = 30) by immunohistochemical and
      morphological observation. The damage to endothelium, hypertrophy and hyperplasia
      of smooth muscle and increament of ECM were found in gastric coronary vein of
      cirrhotic patients. The vessel wall hardened and thickened with decrease of
      elasticity. The results showed that the portal hypertension could accompany with
      portal hypertensive vascular lesions.

PMID- 8758744
TI  - [Selective embolization of coronary vein of the stomach--a new approach for the
      treatment of bleeding from esophageal varices].
AB  - Selective embolization of coronary vein of stomach was employed for the treatment
      of 222 patients with bleeding from esophageal varices due to portal hypertension.
      The coronary vein was separated at middle segment and tube was inserted and
      clamped 5 cm below and above the cardia. The gamma-octyl-cyanoacrylate was used
      for embolization. 19 patients received preventive operation, 106 was subject to
      emergency surgery and 98 patients was treated by elective operation. The bleeding
      of all patients receiving emergency procedure was stopped. 3 died of liver
      failure after operation. 219 survived. 189 cases were followed up for 1-2 years
      and on varices was found. 182 cases followed up for 6 years revealed no relapse
      of bleeding. This technique could achieve good curative effect, which provides a
      new approach for the treatment of bleeding from esophageal varices of portal
      hypertension.

PMID- 8758745
TI  - A scintigraphic study on gastric emptying in patients with non-ulcer dyspepsia.
AB  - Solid gastric emptying rates (GER) were determined with scintigraphic techniques
      in 20 patients with non-ulcer dyspepsia (NUD) and 9 healthy volunteers. GER were
      significantly decreased in NUD patients compared with controls, especially 45 min
      (P < 0.05), 60 and 90 min (P < 0.01) and 120 min (P < 0.05) after ingestion. In
      13 out of 20 NUD patients who demonstrated lower GER, only 4 cases gave a lower
      GER at all stages throughout the determination, the other 9 showed their abnormal
      GER only after 60 min. In 3 cases who received repeated GER studies after
      cisapride therapy, 2 patients showed symptomatic relief accompanied by GER
      improvement. It is concluded that gastric emptying delay may be present with a
      high percentage in patients with non-ulcer dyspepsia. Scintigraphic gastric
      emptying test is a safe and reliable technique with good reproducibility. It may
      be helpful in quantitative study about gastric motion disorders.

PMID- 8758746
TI  - Prevention and management of related complication due to laparoscopic operation:
      pneumothorax, pneumomediastinum and subcutaneous emphysema.
AB  - Essential prerequisite of laparoscopic operation is establishing and maintaining
      pneumoperitoneum with a certain pressure. But under certain circumstances CO2-gas
      insufflating could induce pneumothorax, pneumomediastinum and subcutaneous
      emphysema during the operation. to probe the mechanism of the above
      complications. 2 typical cases were reported with attempt to probe the mechanism
      of the development of such applications. We believe that high intra-abdominal
      pressure during operation is the primary cause of the complications. The
      essentials of prevention and management of such complications were proposed.

PMID- 8758747
TI  - Epiphyseal lengthening operation--an improved technique.
AB  - An improved method of epiphyseal lengthening operation and subsequent outer
      fixation are presented on the basis of experience in 30 cases. The operative
      technique is described in detail, including the different options of separative
      traction and osteotomy at subtrochanteric, distal part of the upper femur and
      lower tibial levels. The physiological and histological research concerning this
      method is discussed. The authors believe that this procedure is better than the
      other methods.

PMID- 8758748
TI  - Treatment of tuberculous pleurisy with effusion by artificial pneumothorax.
AB  - 57 patients were divided into two groups at random. The patients of two groups
      were all given standard treatments with anti-tuberculous drugs. Treatment group
      received artificial pneumothorax to help the cure. Results showed that the
      frequency and quantity of drawing liquid in the treatment group were obviously
      less than those in the control group and the duration of the complete liquid
      absorption was shortened markedly in the treatment group and that total effective
      rate in treatment group (92.5%) was obviously higher than that of the control
      group (83.33%). We found that the artificial pneumothorax could raise the intra
      pleural pressure by 0.20-0.39 kPa, reduce leakage in parietal pleurae and
      increase the absorption in visceral layer evidently. As it can isolate the two
      layers of pleurae from one another by the air in thorax, the incidence of pleurae
      adhesion can be decreased.

PMID- 8758749
TI  - Gingival fibromatosis.
AB  - Presented in this paper is a clinico-pathological report of 11 cases of gingival
      fibromatosis. Of the 11 patients in our series, 2 cases (18.2%) with family
      history began to have symptom from age of 3, which is manifested by the
      involvement of whole gum. 9 patients (81.8%), for which the etiology was unknown,
      had onset of the disease at the periods of deciduous dentition, mixed dentition
      or permanent dentition, with localized or overall involvement of gingiva. The
      disease is characterized by diffuse or localized proliferation of gum.
      Microscopically, the proliferating gum tissue revealed well-developed fibrotic
      structure with few cells; and the fibers were densely arranged without clear
      boundary. The fibrotic tissues showed a diminishing of blood vessels and the
      infiltration of inflammatory cells is not conspicuous.

PMID- 8758750
TI  - C-Ha-ras oncogene in oral leukoplakia tissues.
AB  - The amplification and the G-T mutation at codon 12 of the C-Ha-ras oncogene in
      oral leukoplakia tissues were analyzed by using polymerase chain reaction (PCR)
      and molecular biologic technique. The results showed that these tissues had no
      amplification of Ha-ras oncogene. Only one case harbored G-T mutation in 11 oral
      leukoplakias, but this mutation was absent in 10 normal oral mucosal tissues. The
      possible role and significance of C-Ha-ras oncogene in oral precancerous lesions
      were also discussed.

PMID- 8758751
TI  - Intraoperative use of mitomycin in trabeculectomy.
AB  - Mitomycin (0.2 mg/ml) was applied intraoperatively to 26 glaucomatous patients
      (33 eyes) during conventional trabeculectomy procedure. Most of them were
      considered to be at high risk of surgical failure. The conjunctival flap was
      fornix-based in 9 patients (11 eyes). The success rate was 84.8% without any
      serious side effect.

PMID- 8758752
TI  - BCL-2 protein changes within the hippocampus cells in coriaria lactone-induced
      GTC seizure in rats.

PMID- 8758753
TI  - [Advances in the study of the chemical constituents of gardenia].

PMID- 8758754
TI  - [Development and utilization of medicinal plant resources of Salvia in Anhui].
AB  - In this paper, twenty species (including three forma) of Salvia produced and
      distributed in Anhui, together with a key for their identification are presented.
      Development and utilization of these plant resources, as well as the cause for
      poor quality of Salvia miltiorrhiza at present are also discussed.

PMID- 8758755
TI  - [A comparative study on inorganic elements of guangjiao, buffalo horn and cattle
      horn].
AB  - Determination and comparison were made on the contents of Ca, Mg, Fe, Zn, Cu, Mn,
      Co and Pb in Guangjiao, buffalo horn and cattle horn. The results show that among
      the three species of horns there exist differences as well as similarities.

PMID- 8758756
TI  - [Comparison on the chemical constituents of chuanhonghua I with jianyang
      honghua].
AB  - Based on the qualitative reaction of chemical constituents and TLC, the chemical
      constituents of Chuanhonghua-I were found similar to those Jianyang honghua. The
      effective constituents, safflower haematochrome and safflower yellow contents of
      Chuanhonghua-I, meet the standards of Chinese Pharmacopoeia (Ed. 1990).

PMID- 8758758
TI  - [Esterase isoenzyme of various types in rhizoma Gastrodiae].
AB  - By means of polyacrylamide gel slab electrophoresis, the esterase isoenzyme of
      various types in Gastrodia elata in different growing periods was studied and the
      relativity and difference in physiology and biochemistry were discussed. The
      result reveals that apparent variety of Rhizoma Gastrodiae is not decided by
      genetic factors.

PMID- 8758757
TI  - [Quality of semen Hydnocarpi anthelminiticae introduced to various places].
AB  - The result shows that the Semen Hydnocarpi Anthelminticae introduced in
      Guangdong, Hainan and Yunnan Provinces is similar to the control medicinal
      materials in fatty oil content, index of refraction, effective component content
      and trace element content. But the saponification value of the introduced
      products is higher. The quality of the Semen Hydnocarpi Anthelminticae introduced
      to the above places is up to the level of the control medicinal materials.

PMID- 8758759
TI  - [Quantitative changes of flavonoids in Epimedium koreanum Nakai in different
      collecting periods].
AB  - The quantitative changes of flavonoids in Epimedium koreanum in different
      collecting periods were determined by HPLC and UV spectrophotometry. The result
      shows that the highest content of flavonoids is found in the flowering period
      (May).

PMID- 8758760
TI  - [Comparison of cytotoxicity of different processed products of gamboge on K562
      tumor cells].
AB  - The cytotoxicity of different processed products of Gamboge on K562 tumor cell
      was observed. The result showed that the antitumor action of Garcinia hunburyi
      processed by steaming (0.15MPa, 126 C for 30 min) was the strongest.

PMID- 8758761
TI  - [Determination of pharmacokinetic parameters of shandahuang xiaoyan zhixue
      capsules].
AB  - Based on residual accumulation and biophase availability principles and using
      animal death rate as index, determination has been carried out of the residual
      accumulation rate as well as the toxicokinetic and pharmacokinetic parameters at
      different times of the Shandahuang Xiaoyan Zhixue Capsules.

PMID- 8758762
TI  - [Content determination of baicalin by ultraviolet second order derivative
      spectra].
AB  - By the method of UV second order derivative spectra, baicalin in contents in the
      Lanqin Oral Liquid were determined. Able to eliminate the influence of other
      constituents, this method is simple, rapid, sensitive and accurate.

PMID- 8758763
TI  - [Chemical constituents of Swertia pubescens Franch].
AB  - Four compounds were isolated from Swertia pubescens. They were identified as
      isoorientin, gentiopicroside, glucose and oleanolic acid by chemical and physical
      properties and spectral analysis.

PMID- 8758764
TI  - [Chemical constituents of Coleus carnosifolius Dunn].
AB  - Four compounds were isolated from Coleus carnosifolius. They were identified as
      betulic acid, betulin, oleanic acid and beta-sitosterol by spectral analysis and
      comparison with authentic samples.

PMID- 8758765
TI  - [Determination of flavonol glycosides in the leaf of Ginkgo biloba L. by TLC
      scanning].
AB  - A TLC scanning method for the determination of flavonol glycosides in the leaf of
      Ginkgo biloba has been established. The method includes hydrolysis of the
      flavonoids and subsequent quantitative TLC scanning assay of the aglycones
      obtained. Determinations were carried out with a Shimadzu CS-930 scanner, with
      lambda(S) = 370 nm and lambda(R) = 650 nm. The recoveries were 96.0%-99.6% with
      RSD of 1.03%-2.08%.

PMID- 8758766
TI  - [Determination of chlorogenic acid in Epimedium koreanum Nakai by HPLC].
AB  - The chlorogenic acid content in Epimedium koreanum was determined by HPLC. The
      result shows that this method is simple, specific and accurate. The recovery was
      97.5% and relative standard deviation was 1.4%. With good reproducibility and
      wide response linearity, the method can be used for the quality control of this
      herbal medicine.

PMID- 8758767
TI  - [Effects of total saponins of semen ziziphi Spinosae on brain damages and brain
      biochemical parameters under cerebral ischemia of rats].
AB  - Total saponins of Semen Ziziphi Spinosae (ZS) can reduce the contents of water
      and MDA in ischemic rat's brain tissues, elevate the activity of SOD, CK and LDH,
      cut down the content of lactate and alleviate the damages of nerve cells in
      brain. The study shows that ZS possesses protective effects on cerebral ischemic
      injuries.

PMID- 8758769
TI  - [Effects of neferine on the 45Ca-influx and efflux induced by activation of alpha
      1 adrenoceptor of vascular smooth muscle].
AB  - Experiments have shown that in the vascular smooth muscle neferine (Nef) can
      markedly reduce the 45Ca-influx induced by phenylephrine, but does not affect the
      45Ca-influx induced by mmol/L KCl, which is almost completely inhibited by
      nifedipine. Neferine does not inhibit 45Ca-efflux.

PMID- 8758768
TI  - [Inhibitory action of Chinese compound prescription for reinforcing vital energy
      and invigorating blood circulation on cancer cell multiplication].
AB  - Experiments have proved that the Chinese compound prescription for reinforcing
      vital energy and invigorating blood circulation markedly helps to improve the
      morphology of cancer cell nucleolus and membrane surface microvillus, amend the
      composition of microtubulin and facilitate intercellular gap junctional
      communication. Cell cycle kinetics shows that the multiplication of cancer cells
      in human stomach is checked mainly at G2M stage.

PMID- 8758770
TI  - [Problems and measures of diagnosis and treatment of gestational trophoblastic
      disease].

PMID- 8758771
TI  - [Selective arterial catheterization in the management of drug-resistant
      choriocarcinoma].
AB  - OBJECTIVE: In order to save the life of the patients with drug-resistant
      choriocarcinoma due to improper treatment, selective arterial catheterization was
      used. METHODS: All the 71 cases were treated with systemic chemotherapy together
      with pelvic selective arterial chemotherapy. 5 of them had arterial chemotherapy
      plus arterial embolization for hemorrhage. In 13 patients who had lung
      metastasis, intraarterial injection of methotrexate (MTX) through bronchial
      arterial was added. RESULTS: 55 of 71 (77.8%) achieved complete remission and 10
      (14.1%) had partial remission. One patient failed to follow-up. 5 died of various
      causes during hospitalization. On Follow-up 12 had survived for more than 5 years
      with no signs of recurrence. 2 of them had childbirth after recovery. CONCLUSION:
      Systemic intravenous infusion chemotherapy in combination with arterial
      chemotherapy is useful for drug-resistant choriocarcinoma. In patients with
      intraperitoneal hemorrhage caused by tumor rupture, selective arterial
      embolization should be used as emergency treatment to effectively control the
      bleeding, in order that patients will have a chance for further chemotherapy.

PMID- 8758772
TI  - [The study of DNA fingerprint of hydatidiform moles and the clinical outcome].
AB  - OBJECTIVE: To study the genetic origin of hydatidiform moles (HM) and the
      clinical outcome. METHODS: 41 cases of hydatidiform mole were collected mainly
      from Beijing area and studied for genetic components by DNA fingerprints. The
      diagnosis of persistent gestational trophoblastic disease (PTD) was made if blood
      hCG remained higher than normal 8 weeks after mole evacuation. RESULTS: Among 41
      HM samples, 32 produced identifiable DNA fingerprints. DNA from only paternal
      origin was found in 21, in which 6 were PTD, DNA from both parents in 11, none of
      which developed PTD. CONCLUSIONS: DNA from only paternal origin was more
      frequently found than from both parents in HM, and there was a higher risk of PTD
      in the former group than in the latter.

PMID- 8758773
TI  - [Study on cellular proliferation activity of placental site trophoblastic tumor].
AB  - OBJECTIVE: To study the relationship among the cellular proliferation activity,
      benign clinical process and pathologic characteristics of placental site
      trophoblastic tumor (PSTT). METHODS: Paraffin-embedded blocks from ten patients
      with PSTT were reexamined by mitotic count, argyrophilic nucleolar organizer
      regions (AgNOR) staining and flow cytometric DNA analysis. Five cases of
      hydatidiform mole (HM) and 5 choriocarcinoma (CC) were chosen as controls.
      RESULTS: Mean mitotic figures of PSTT were 1.3 (0-3) per 10 high power field,
      while those of HM and CC were 0.8 (0-2) and 2.2 (1-4) respectively. AgNOR number
      of PSTT was 2.70 +/- 0.55 per cell, while those of HM and CC were 1.96 +/- 0.38
      and 4.50 +/- 0.73 respectively. Flow cytometric DNA content revealed that PSTT
      had DNA index (DI) of 1.10, S phase of 16.7% and proliferating index (PI) of
      26.6%. Eight of 10 Cases were followed up, 7 are alive and 1 died of primary lung
      cancer. CONCLUSION: PSTT has relative low cellular proliferation activity. The
      good clinical procedure and benign pathological feature of PSTT may be associated
      with its diploidy DNA and low cellular proliferation activity.

PMID- 8758774
TI  - [Diagnostic value of color Doppler flow imaging in gestational trophoblastic
      diseases].
AB  - OBJECTIVE: To investigate the value of color doppler flow imaging (CDFI) and
      pulsed doppler (PD) determinations in early diagnosis, evaluation of therapeutic
      effects and prediction of prognosis of gestational trophoblastic diseases (GTD).
      METHOD: CDFI and PD were performed in 55 cases of GTD and 30 normal pregnant
      women as controls. RESULTS: The uterine muscular layer in GTD showed multicolored
      abundant blood flow and blood sinuses. Blood flow resistance was low with a
      resistance index (RI) less than 0.5. After chemotherapy the RI changed
      dramatically. Pathological evidences were found in surgical specimens of 8
      patients. Findings of pelvic hysterography in 16 cases were in accordance with
      the results of CDFI and PD determinations. CONCLUSION: CDFI and PD as new methods
      for early diagnosis of GTD can also be used to evaluate the chemotherapeutic
      results as well as to determine the prognosis of the disease.

PMID- 8758775
TI  - [Combination chemotherapy of 5-fluorouracil and nitrocaphane for the treatment of
      malignant trophoblastic tumor].
AB  - OBJECTIVE: To evaluate the effectiveness, side effects and long term result of
      combination protocol of 5-fluorouracil (5-FU) and nitrocaphane (AT1258) on
      patients with malignant trophoblastic tumor. METHODS: The chart and follow up
      data of 166 patients treated from 1979 to 1988 in Liaoning Province Tumor
      Hospital were reviewed. 136 invasive mole and 30 choriocarcinoma were treated by
      a 5-FU and AT1258 combined protocol. Their immediate treatment results, side
      effects and long-term follow-ups were retrospectively analysed. RESULTS: The
      complete remission rate of invasion mole was 100.0% and choriocarcinoma 86.7%.
      The accumulative 5 and 10 year's survival rate for invasive mole were 100.0% and
      99.3%, while 85.8% and 85.8% for choriocarcinoma. None of this group died of side
      effects or complication. CONCLUSION: 5-FU and AT1258 combination chemotherapy may
      be a protocol of choice in the treatment of malignant trophoblastic tumor.

PMID- 8758776
TI  - [A study on DNA content and cell cycle phase analysis in endometrial carcinoma].
AB  - OBJECTIVE: To study the prognostic value of DNA content, cell cycle phase in
      endometrial carcinoma. METHODS: DNA content and cell cycle phase analysis were
      performed on 100 paraffin-embedded archival specimens from 103 cases of
      endometrial carcinoma using flow cytometry. RESULTS: Aneuploidy was found in
      71.0% of specimens. The aneuploidy rate in specimens from grade III, deep
      myometrial invasion and stage III, IV was significantly higher than that in
      specimens from grade I, nonmyometrial invasion and stage I (P < 0.05
      respectively). 5-year survival rate for patients with aneuploidy was 65.9% and
      for patients with diploidy was 87.6% (P < 0.01). High S-phase fraction (SPF) was
      associated with high grade, deep myometrial invasion and advanced stage. The mean
      SPF was 13.4% in the living group and 17% in the dead group. The 5-year survival
      rate for patients with SPF > 17% was 50.4% and for patients with SPF < 17% was
      79.1% (P < 0.01). SPF and stage were the most important prognostic factors in
      endometrial carcinoma by Cox's proportional hazards model. CONCLUSIONS: DNA
      ploidy and SPF were found to be of important prognostic indicators in endometrial
      carcinoma.

PMID- 8758777
TI  - [Changes in plasma endothelin-1 and lipid peroxidate levels and amount of
      superoxidate dismutase in red blood cell in patients with pregnancy-induced
      hypertension].
AB  - OBJECTIVE: To evaluate the role of endothelin (ET-1) and lipid peroxide (LPO) in
      the pathogenesis of pregnancy-induced hypertension (PIH). METHODS: The plasma
      concentrations of ET-1, LPO and the amount of superoxide dismutase (SOD) in red
      blood cell were measured by radioimmunoassay, thiobarbituric acid fluorimetric
      determination and catechol self-oxidation determination respectively in total 95
      women (normal non-pregnant women 15, Late pregnant women 20 and patients with PIH
      60). RESULTS: (1) The levels of ET-1, LPO and SOD in normal late pregnant women
      were significantly higher than those in non-pregnant women (P < 0.01), but the
      LPO/SOD ratio was not significantly different between the two groups. (2) The
      levels of plasma ET-1 and LPO/SOD ratio in cases with PIH were markedly higher
      than those in normal late pregnant women, and it increased with the severity of
      the disease and returned to the levels of normal late pregnant women within 3-7
      days after delivery. (3) There was a positive correlation between ET-1 and
      LPO/SOD ratio in PIH. CONCLUSIONS: The imbalance of oxidation and antioxidation
      and endothelial cell injury may play an important role in the pathogenesis of
      PIH.

PMID- 8758778
TI  - [Study on infertility caused by infections of Chlamydia trachomatis and
      ureaplasma urealyticum].
AB  - OBJECTIVE: To explore the effects of chlamydia trachomatis (CT) and ureaplasma
      urealyticum (UU) infections on male and female infertility. METHODS: Samples from
      cervical canal or male urethra of 1198 infertile patients (599 couples) were
      studied and from 167 normal fertile men and women served as control. The
      fluorescent monoclonal antibody technique and the culture method were used for CT
      and UU assays respectively. RESULTS: The positive rates of CT and UU infections
      in infertile group were 25.5% (306/1 198) and 35.9% (167/1 198) respectively,
      while 6.6% (11/167) and 15.6% (26/167) in the control group respectively. There
      were significant differences between the 2 groups (P < 0.01). After treatment of
      positive patients, the pregnancy rates were higher in those patients became
      negative than that in patients remained positive (P < 0.01). CONCLUSION: The CT
      and UU infections were one of the factors causing infertility.

PMID- 8758779
TI  - [Addison's disease in pregnancy: a report of six cases].
AB  - OBJECTIVE: To review six cases of pregnancy with Addison's disease at Obstetrics
      and Gynecology Hospital, Shanghai Medical University from 1949 to 1994. METHOD:
      This is a clinical retrospective analysis. Five of the 6 patients were treated
      with hormone replacement therapy, and the remaining one received no hormone
      treatment due to lack of symptoms during pregnancy and neglect of previous
      adrenal surgery by obstetricians. RESULTS: The patient received no treatment
      occurred Addisonian crisis and died soon after delivery. The other five patients
      had smooth course of delivery and postpartum period. CONCLUSIONS: Hormone
      replacement therapy is important for patients with Addison's disease in pregnancy
      especially for acute decompensation of adrenal function. Pregnant women with
      history of adrenal surgery should be monitored carefully even without any
      symptoms and hormone treatment is necessary. Vaginal delivery is encouraged
      unless there is obstetric indication.

PMID- 8758780
TI  - [Clinical analysis of bacterial vaginosis in 76 cases].
AB  - OBJECTIVE: To study the clinical manifestation and treatment of bacterial
      vaginosis (BV). METHODS: The criteria used for diagnosis were the presence of
      clue cells by wet mount slide or gram stain, plus at least 2 of the following 3
      signs and symptoms: (1) vaginal discharge with pH > 4.5; (2) an increased thin
      homogeneous vaginal discharge; (3) positive amine test. From 1994, 1 to 1995, 3,
      a total of 76 cases with BV who had good follow up were diagnosed and treated by
      Kejunning (a combination of chinese traditional herb medicine), Shuangzuotai
      (combined metronidazole vaginal suppository), metronidazole, etc. RESULTS: For
      BV, the presence of clue cells is a prerequisite for diagnosis. Vaginal discharge
      with pH > 4.5 and positive amine test were present in all the cases. Increased
      white thin homogeneous vaginal fluid were found in 96.1% (73/76) of the cases.
      79.0% of the patients complained of fishy odor vaginal discharge. Treatment with
      antibiotics or Shuangzuotai were effective. Kejunning had a cure rate of 70.0%
      one month after treatment. CONCLUSIONS: The detection of clue cell is an
      important diagnostic criterion. Besides metronidazole, Kejunning had a good
      result for the treatment of BV as well.

PMID- 8758782
TI  - [Improving quality of obstetric care for safe motherhood].

PMID- 8758781
TI  - [Hereditary ovarian cancer syndrome].

PMID- 8758783
TI  - [Summary of National Symposium on Improving Quality of Obstetric Care for Safe
      Motherhood].

PMID- 8758784
TI  - [Obstetric quality investigation on urban and rural area in China].
AB  - OBJECTIVE: A survey on implementing the proclamation in "National plan of action
      for the survival, protection and development of children in 1990s" in China
      (NPA), by reducing the maternal mortality rate (MMR) by half and the infant
      mortality rate (IMR) by 1/3 by the year 2000 as a proof of improved obstetric
      quality. METHOD: The maternal and child health (MCH) bureau, ministry of health,
      have called on a cooperative investigation on obstetric quality in 75 obstetric
      clinics in 11 provinces, municipalities or autonomous regions, randomly sampled
      from each of the 6 governmental areas in China. The data were collected and
      analyzed centrally, together with the yearly reports from the monitored county
      hospitals. RESULTS: Senior medical professionals associated to 32.68% in
      provincial and teaching hospitals while only 2.63% in the country hospitals. The
      former are provided with all necessary equipment while the latter with inadequate
      and outdated ones. MMR declined year by year, more marked wherever hospital
      delivery rate was high and when the numbers of antenatal visit were more.
      However, when antenatal visit began late in pregnancy, MMR rose Zhejiang province
      and Shanghai ranked first in obstetric quality because of an efficient systematic
      management of the pregnancies. CONCLUSIONS: Having enough leading professionals
      in this specialty to train adequate medical ground personnel at grass root level;
      providing sufficient medical installations; enforcing easily and good quality
      antenatal care and increasing hospital deliveries carried out under authoritative
      management are important points to raise the quality of obstetrics.

PMID- 8758785
TI  - [The changing trend of cesarean section rates in 35 years].
AB  - OBJECTIVE: To investigate the changing trend of cesarean section rates in 35
      years. METHODS: Samples taken from 4 months (March, June, September, December) of
      a year every 5 years in 35 years (from 1959 to 1994) were analysed and a total of
      1 667 cases were collected. RESULTS: Cesarean section rates increased since 1975
      and particularly from 1980 to 1994. The causes of this trend may be related to
      following reasons. (1) Improvement of skill and safety of operation. (2) Change
      of indications of cesarean section. (3) Social factors. CONCLUSION: The decrease
      of perinatal mortality rate was not relevant only to the cesarean section rate,
      but dependent more on good perinatal care.

PMID- 8758786
TI  - [Clinical analysis of 62 pregnant women complicated with organic heart diseases].
AB  - OBJECTIVE: To investigate the factors which effect maternal-fetal outcomes in
      pregnant women complicated with organic heart disease. METHOD: Clinical data of
      62 pregnant cases with either rheumatic or congenital heart diseases, collected
      from Beijing Anzhen Hospital during 1985-1994, were analysed retrospectively.
      RESULTS: The prevalence of organic heart diseases in total pregnant women during
      the same period was 0.97%. No significant difference was found in maternal-fetal
      complications between the two types of heart diseases. However, the incidences of
      maternal heart failure, premature birth, intrauterine growth retardation were
      significantly higher in patients without previous surgical treatment as compared
      with those with previous surgical therapy, and were also higher in patients with
      heart function of grade III-IV in comparison with those with grade I-II.
      CONCLUSIONS: Patients with organic heart diseases should be treated and operated
      on in order to achieve grade I-II heart function before pregnancy. Cesarean
      section is the better choice of delivery.

PMID- 8758787
TI  - [Study on evaluation of fetal scalp tissue pH value during labor].
AB  - OBJECTIVE: To assess the predictive value of serial monitoring fetal scalp tissue
      pH value (tpH) during labor. METHOD: Fifty two primipara with singleton and
      cephalic presentation were recruited during their active phase of labor after
      rupture of membrane. Their fetal scalp tpH were determined by a new type of alloy
      pH spiral electrode and pH-LS-1 sensor. These values were compared with the
      umbilical blood pH values (bpH) measured immediately after delivery. RESULTS: The
      fetal tpH values were significantly positive correlated with the bpH values (r =
      0.822 and 0.725). The incidence of neonate asphyxia in tpH >or= 7.20 group was
      significantly lower than those to tpH<7.15 group. No adverse effect was observed
      in this study. CONCLUSION: Determination of fetal scalp tpH during labor is of
      predictive value and harmless fro detecting fetal distress.

PMID- 8758788
TI  - [Study of the relationship between complement activation and vascular endothelial
      damage in pregnancy induced hypertension].
AB  - OBJECTIVE: To evaluate the relationship between complement activation and
      vascular endothelial damage in pregnancy induced hypertension (PIH). METHODS: We
      quantified C1q, B-factor (BF) and C1-inhibitor (C1-INH) in peripheral and
      retroplacental sera of 35 nulliparous PIH patients and 20 normotensive controls
      with double antibody sandwich ELISA. Circulating endothelial cell (CEC)of the two
      groups were isolated with the density gradient system of Percoll liquid and
      counted under microscope. The correlation between CEC and C1q was analysed.
      RESULTS: (1) C1q concentrations in peripheral and retroplacental sera were
      significantly decreased in PIH patients than that in normotensive controls,
      however, the concentrations of BF and C1-INH were significantly elevated in PIH
      patients. The changes in retroplacental serum were much more profound than those
      in peripheral serum. (2) The count of CEC was significantly increased in PIH
      patients than that in controls. (3) The count of CEC was negatively correlated to
      C1q concentration. CONCLUSIONS: Not only the classical complement activation
      pathway but also the alternative complement activation pathway and complement
      regulatory protein play important roles in the pathogenesis of PIH, and
      complement activation and vascular endothelial damage is correlated. Evaluation
      of C1q, BF, C1-INH and CEC may be of value in clinical monitoring and management
      of PIH.

PMID- 8758789
TI  - [Effects of diagnostic ultrasound on villus ultrastructure of early pregnancy].
AB  - OBJECTIVE: To evaluate the effects of diagnostic ultrasound on villus
      ultrastructure of early pregnancy. METHODS: Using the electron microscopy, the
      effect of B-mode ultrasound and color Doppler flow image on villus of early
      pregnancy were studied. 46 cases of early pregnancy women were divided into five
      groups: Groups 1 : control group; Group II and III: 24 +/- 1 hours after exposure
      to B mode and color Doppler ultrasound for 30 minutes respectively; Group IV and
      V: 72 +/- 1 hours after exposure to B mode and color Doppler ultrasound for 30
      minutes respectively. RESULTS: Expansion of perinuclear space in cytotrophoblasts
      and syncytiotrophoblasts, enlargement of rough endoplasmic reticulum, and
      vacuolization in the cytoplasm were found in Group II and III. CONCLUSIONS: The
      present study showed that the main injured sites after exposure to ultrasound
      were the plasma membrane and suborganelles. These changes disappeared within 3
      days.

PMID- 8758790
TI  - [Pharmacokinetic study of intraperitoneal chemotherapy with high-dose cisplatin
      for advanced ovarian cancer].
AB  - OBJECTIVE: To determine the characteristics of pharmacokinetics with high-dose
      cisplatin (DDP) instilled intraperitoneally and its toxicity as compared with
      that by intravenous (i.v.) route of administration (i.p.). METHODS: Sixteen
      patients with advanced ovarian cancer, not previously treated, were randomly
      divided into two groups: every patient in group I received intraperitoneal
      administration of DDP (100mg/m2) and those in group II received the same dose of
      DDP by intravenous route. The blood, ascitic fluid and urine were collected in
      different intervals as scheduled for 8 days after administration of these drugs.
      The total platinum of all samples were measured by a flameless type of atomic
      absorption spectrometry. RESULTS: The concentration of total platinum in the
      ascitic fluid was very high in i.p. group. The area under the concentration-time
      curve (AUC) for total platinum in ascitic fluid after i.p. therapy was 5 folds
      greater than that after i.v. therapy (P < 0.05). The total platinum concentration
      in serum after i.p. therapy was about the same as that after i.v. therapy. The
      half-life time for the elimination phase of total platinum from ascitic fluid and
      serum after i.p. administration was longer than that after i.v. administration.
      The toxicity of high-dose DDP given i.p. was not increased as compared with that
      given i.v.. CONCLUSIONS: This study indicates that high-dose DDP i.p. therapy
      offers some advantages in the treatment of ovarian cancer. The tumor tissues and
      peritoneal growths could be bathed in a high concentrations of DDP with a longer
      duration, so that the tumorcidal effect may be increased. The drug concentration
      in serum after i.p. therapy was as high as i.v. route. The toxicity of high-dose
      DDP i.p. therapy was not higher than that of i.v. therapy.

PMID- 8758791
TI  - [Comparison of human papilloma virus-DNA in condyloma acuminatum, cervical cancer
      and the female genital tract].
AB  - OBJECTIVE: To examine human papilloma virus (HPV) infection rate and types in
      several lesions of the genital tract and to observe the relation between HPV and
      host cells for differential handling of cases and for early diagnosis. METHODS:
      Tissues from 89 cases of condyloma acuminata, 76 cases of cervical cancer and
      swabs from 198 cases of normal vaginal were analysed by polymerase chain reaction
      for HPV infective rate. Main HPV types were compared and Southern blot was used
      to compare the physical pattern of HPV in condyloma acuminata and cervical
      cancer. RESULTS: The positive rates of HPV-DNA in condyloma acuminata and
      cervical cancer were respectively 98.9% and 94.7%. The primary types of the
      former were HPV 6, 11 and of the latter mainly 16 and 18. The latent infective
      rates in normal vagina was 37.4%, among which, HPV 6, 11, 16, 18 consisted of
      only 21.6%. HPV11-DNA in condyloma acuminata existed mainly in episodic form.
      Most of HPV16-DNA in cervical cancer integrates into the host cells with
      variation. CONCLUSIONS: The different types of HPV are related to particular
      morphology and characteristics of lesions. The relation of HPV-DNA to host cell
      and can offer some reference for the determination of the character of the
      lesion, and it may be award of malignant transformation.

PMID- 8758792
TI  - [Gonadotropins stimulate the proliferation of human epithelial ovarian cancer
      cell].
AB  - OBJECTIVE: To observe the effect of FSH and LH on the proliferation of human
      epithelial ovarian cancer cell. METHOD: Human epithelial ovarian cancer AO cells
      were incubated with follicle stimulating hormone (FSH) and luteinizing hormone
      (LH) (2U/L and 2.5U/L respectively). They were detected for proliferation by the
      use of the immunohistochemical technique and morphology. RESULTS: The positive
      rate of proliferating cell nuclear antigen expressed in the cancer cell was
      increased significantly (p < 0.05) indicating its proliferation stimulating
      effect by FSH. The mitosis of cancer cells was increased by FSH and by LH (35%,
      16% respectively). CONCLUSIONS: It is suggested that FSH and LH can stimulate the
      proliferation of epithelial ovarian cancer cell, and they may play an important
      in the development of epithelial ovarian cancer.

PMID- 8758793
TI  - [Effect of antisense c-erbB2 on biologic behaviour and chemotherapeutic drug
      sensitivity in human ovarian cancer cells].
AB  - OBJECTIVE: To explore the effects of antisense erbB2 on the biological behaviours
      and on chemotherapeutic drug sensitivity in human ovarian cancer cells. METHODS:
      A recombinant retroviral expression vector: pDOR-erbB-neo was constructed which
      contain the neomycin resistant gene and the erbB2 cDNA 3.8kb antisense fragment.
      pDOR-erbB-neo was introduced into human ovarian cancer cell line SKOV3 by
      lipofectin. The cells were selected with geneticin (G418). The cells transfected
      with pDOR-erbB-neo were named SKOV3-A2. RESULTS: Southern blot analysis confirmed
      the presence of the antisense erbB2 in transfected cells. Transfected cells
      showed no obvious changes in morphology. Compared with parental cells and with
      pDOR-neo transfected cells used as controls, the growth and DNA synthesis of
      antisense transfected cells, SKOV3-A2, were inhibited. Transfection with pDOR
      erbB-neo rendered the cells significantly, more sensitive to chemotherapeutic
      drugs (5-fluorouracil, cisplatinum) than the parental cells. CONCLUSIONS: The
      effectiveness and the potentiality of antisense erbB2 in ovarian cancer gene
      therapy is demonstrated. c-erbB2 oncogene may be related to drug resistance in
      ovarian cancer cell.

PMID- 8758794
TI  - [Relation between progesterone and pathogenesis of uterine leiomyomas].

PMID- 8758795
TI  - [Current status and trends in chemotherapy of ovarian cancer].

PMID- 8758796
TI  - [Summary of the National Conference on Chemotherapy of Gynecological
      Malignancies].

PMID- 8758797
TI  - [Experimental study on the mechanism of cisplatin resistance and its reversion in
      human ovarian cancer].
AB  - OBJECTIVE: To explore the mechanism of cisplatin resistance and its reversion in
      human ovarian cancer. METHODS: A xenografted cisplatin resistant mice model of
      human ovarian cancer, SKOV3/cp, was developed by the microencapsulated technique.
      The multiple changes of bio-chemical markers in the model were determined, and
      various modulators for reversion were tested. RESULTS: Intracellular platinum
      accumulation in SKOV3 was 5.1 times, Pt-DNA adducts 2.4 times and interstrand
      cross link of DNA (ISC) 4.8 times of those in cisplatin-resistant cell line,
      SKOV3/cp. These changes in SKOV3/cp could not be reversed by verapamil.
      Amphotercin B (AmB) and Novobiocin (NVB) could raise the concentrations of
      platinum and Pt-DNA adducts in SKOV3/cp, resulting in complete or partial
      reversion of cisplatin-resistance of SKOV3/cp. There were no differences in total
      glutathione (GSH) level and in sensitivity to CdCl2 between SKOV3 and SKOV3/cp.
      CONCLUSIONS: It is suggested that the primary factor causing SKOV3/cp resistance
      to cisplatin is the reduction of intracellular platinum accumulation and the
      augmentation of the ability to remove Pt-DNA adducts. The resistance is not
      considered to be associated with the multidrug resistant, GSH, metallothionein
      systems. AmB and NVB can overcome cisplatin resistance of SKOV3/cp in vitro and
      in vivo.

PMID- 8758798
TI  - [The evaluation of adenosine triphosphate bioluminescence assay for
      chemosensitivity testing of ovarian cancer cell line].
AB  - OBJECTIVE: To assess the efficacy of adenosine triphosphate (ATP) assay for
      chemosensitity testing of ovarian cancer cell line and to compare its predicting
      value with that of diphenyltetrazolium bromide (MTT) test. METHODS: By using ATP
      assay and MTT test the cytotoxic effect of 7 anticancer drugs on ovarian cancer
      cell line AO were determined. The sensitivity and stability of ATP assay were
      compared with those of MTT test. The optimal time of exposure of the cells to the
      drugs before doing ATP chemosensitity assay is investigated. RESULTS: (1) The
      results obtained by ATP assay correlate well with that by MTT test (r = 0.918 1).
      However, in 90% of the assay samples the cytotoxic effect of the chemotherapeutic
      agents on cancer cells detected by ATP assay was 10% or more stronger as compared
      with that determined by MTT test. The difference in sensitivity of the two assays
      was also demonstrated by the least number of living cells. A change of living
      cells of 60 per well could be detected by ATP assay while that detected by MTT
      test should be 200 per well. (2) By repeating the tests of a same batch of
      samples for 5 times, it revealed that the results obtained by ATP assay was more
      stable than MTT test. The difference between the sx- (standard error) of the two
      tests was significant (P < 0.05). (3) The optimal time of exposure of the cancer
      cells to the anticancer drugs for testing its chemosensitivity was 5 days.
      CONCLUSIONS: The method of ATP assay for chemosensitivity test is simple and
      convenient with high sensitivity and stability. It may be used as a new in vitro
      chemosensitivity test in patients with ovarian cancer.

PMID- 8758799
TI  - [The roles of tamoxifen in the treatment of pre- and post-menopausal endometrial
      carcinoma patients].
AB  - OBJECTIVE: To investigate the role of tamoxifen in the treatment of pre- and post
      menopausal patients with endometrial carcinoma, its mechanism and effects.
      METHODS: Forty patients of endometrial cancer were divided into pre- and post
      menopausal groups. Each group was treated with oral tamoxifen 20mg three times
      per day for 10 days. The changes of serum levels of sex hormones, levels of
      estrogen and progesterone receptor (ER, PR) in carcinoma tissue as well as
      histopathologic changes following tamoxifen treatments were observed and
      compared. RESULTS: Histological changes showed that the cell nucleus to cell
      plasma ratio decreased, the nuclear mitoses reduced and the nuclear shape varied
      from stick to circular, indicating a tendency of cancer cells towards better
      differentiation. For pre-menopausal patients, follicle-stimulating hormone (FSH)
      increased, the concentration of ER either rose or went down while PR increased.
      For post-menopausal patients, FSH decreased, the concentrations of ER and PR were
      mainly on the increase. CONCLUSION: Tamoxifen was effective in treating patients
      with endometrial cancer. For pre-menopausal patients, it acted as an
      antioestrogen. For post-menopausal patients, it acted as a weak oestrogen.

PMID- 8758800
TI  - [Cardiotoxicity of 5-fluorouracil].
AB  - OBJECTIVE: To determine the possibility and magnitude of cardiotoxicity following
      high dose intravenous infusion of fluorouracil (5-FU). METHODS: A prospective
      clinical study was performed on 104 patients with choriocarcinoma and invasive
      mole. 5-FU was administered by slow intravenous infusion in 5% glucose 500 ml for
      8 hours at doses of 28-30 mg.kg-1.day-1 when used as a single agent treatment or
      24-26 mg.kg-1.day-1 when used in combination with kengshengmycin (KSM). The total
      cycles of treatment with 5-FU + KSM were 109 and those of 5-FU or KSM each used
      as a single agent were 71 and 12 respectively. The cardiac functions were
      monitored by cardiac symptoms, ECG and serum cardiac enzymes before and after 5
      FU infusion. RESULTS: Among the 192 treatment cycles tachycardia, palpitation or
      cardiac distress were observed in 14 cycles. ECG showed changes of ST or T waves
      in 8 cycles, sinus tachycardia in 3 cycles. The results of serum cardiac enzyme
      determinations were variable. The diagnostic criteria of cardiotoxicity were
      appearances of abnormalities manifested in any two of the three monitor items.
      The incidence of cardiotoxicity was 4.2% in 5-FU group, 4.6% in 5-FU + KSM group
      and 0% in KSM group. All episodes were mild, reversible spontaneously after
      cessation of chemotherapy and did not reappear in subsequent chemotherapeutic
      cycles. Seven patients with definite cardiac diseases before chemotherapy were
      given 5-FU treatment, but no obvious aggravation of cardiotoxicities were
      observed even with repeated 5-FU treatments. CONCLUSION: Only occasional
      cardiotoxicities were observed in 5-FU treatments. They were rather mild and
      reversible. The incidence of cardiotoxicity might be reduced with emphasis on
      strict observance of the treatment regimen in regard to the dosage used, the
      speed of the infusion and attention to the treatment of any side-effects.

PMID- 8758801
TI  - [The relationship between placental pathology and certain pathogens detected in
      paraffin-embedded tissues in cases of intrauterine growth retardation].
AB  - OBJECTIVE: To study the relationship between placental pathology and certain
      pathogens detected in paraffin-embedded placental tissues in cases of
      intrauterine growth retardation (IUGR). METHODS: The PCR-DNA techniques were used
      for determination of pathogens, including toxoplasma, cytomegalovirus and herps
      simplex type II in paraffin-embedded placental tissues from 53 cases of IUGR.
      RESULTS: Among 53 cases of IUGR, the pathogens were detected in 19 cases
      (35.85%). The relationships of pathogens detected to placental pathology were
      analyzed. Pathogens were found in 10 of 18 placentas with villitis, 7 of 11
      placentas with villous maturation retarded and 2 of 3 intervillous space
      infections respectively. The incidence of infection in the pathological placentas
      was 59.38%. CONCLUSIONS: The study suggested that the haematogenous infections
      could play important roles in unknown causes of IUGR.

PMID- 8758802
TI  - [A comparison of plasma amino acid concentrations between appropriate and small
      for gestational age fetuses].
AB  - OBJECTIVE: To investigate the role of amino acid played in pathogenesis of small
      for gestational age (SGA) fetuses. METHODS: Plasma amino acids' concentrations
      (PAAC) of umbilical venous samples obtained by cordocentesis before labor or at
      cesarean section were measured in 30 cases of appropriate for gestational age
      (AGA) fetuses at different gestational age. PAAC of both mother and fetuses were
      measured and compared in 10 cases of SGA and 10 cases of AGA. RESULTS: In cases
      of AGA, the PAAC in fetuses (3.11 +/- 0.41 mmol/L) were found to be higher than
      that in mothers. There were significant correlations between fetal and maternal
      PAAC. The total PAAC in mothers and fetuses, and its ratios were not changed with
      gestational age. In cases of SGA, essential amino acids' concentration (EAA),
      especially branch chain amino acid (BCAA) and lysine, decreased significantly.
      The feto-maternal ratios of EAA and BCAA were reduced significantly, whereas
      concentrations of EAA and BCAA in mothers did not change significantly.
      CONCLUSIONS: The results indicated that placental function and maternal nutrient
      supplement were important factors for maintaining fetal growth and development.
      In AGA cases, relationship of PAAC between mothers and fetuses were kept in a
      stable balance. In SGA fetuses certain amino acid metabolic disturbances existed.
      The reduction of some PAAC was not due to their decrease in mothers.

PMID- 8758804
TI  - [A clinical-pathological study on hypoxic ischemic encephalopathy in 124 cases of
      perinates].
AB  - OBJECTIVE: To explore the morphological feature, its pathogenesis and clinical
      significance of hypoxic-ischemic encephalopathy (HIE) through pathological
      examinations. METHODS: In addition to the routine pathologic examination, the
      brain tissues, including frontal lobus, temporal lobus, occipital lobus,
      hippocampus, capsula interna, cerebellum and medullary bulb, were sectioned and
      examined respectively. RESULTS: (1) 93.5% of cases had a history of direct or
      indirect asphyxia. (2) The main pathological alterations were edema, congestion,
      hyaline thrombosis, haemorrhage, degeneration and necrosis of nerve cells.
      Softening, calcification, cavity formation and fibrosis were also seen in some
      cases. CONCLUSIONS: The study suggested that congestion and edema of cerebral
      tissue were essential changes for the pathogenesis of HIE. Hemorrhage and
      necrosis were common pathological alterations. Fibrosis and cavitation were
      changes of convalescence. It is of primary importance to treat asphyxia during
      perinatal period for the prevention of HIE.

PMID- 8758803
TI  - [An experimental study on the treatment of fetal rabbits with intrauterine growth
      retardation].
AB  - OBJECTIVE: To investigate the effect of histocyte activators and vasodilators on
      the amino acids concentration in fetal rabbits with intrauterine growth
      retardation (IUGR). METHODS: The rabbits with IUGR were caused by passive smoking
      and treated with histocyte activators (adenosine triphosphatase, coenzyme A,
      cytochrome C, and vasodilators (injectio salviac molfiorrhizae composita,
      anisodamine). The effects of different remedies on the fetal plasma amino acids'
      concentration and the fetal development (i.e. birth weight, the weights of fetal
      liver and fetal brain) were studied. RESULTS: Both histocyte activators and
      vasodilators had favorable effects on the improvement of fetal development and
      the increase of fetal plasma amino acids' concentration. But the action of
      histocyte activators was stronger than vasodilators. CONCLUSIONS: The results
      suggested that vasodilators could improve the uterine-placental flow, and
      histocyte activators could enhance placental transfer of amino acids. But
      histocyte activators seem to be better than vasodilators.

PMID- 8758806
TI  - [Detection of placental alkaline phosphatase in ovarian cancer].
AB  - OBJECTIVE: To establish a method for diagnosis of malignant tumors by
      determination of the placental alkaline phosphatase (PLAP) in serum. METHODS: A
      solid phase enzyme immunoassay was adopated by an antibody against PLAP. PLAP in
      serum of 81 patients with malignant tumor and 86 healthy people as control were
      determined. RESULTS: In the control group, the PLAP activity showed deviative
      distribution, the 95th percentile values of PLAP in control group was 3.8U/L. If
      this value served as normal cut-off line, 18 cases among 81 patients with
      malignant tumors were positive. The positive rate was 22.2%, but the positive
      rates in ovarian cancer was 61.9%. CONCLUSIONS: The increasing of serum PLAP may
      be helpful for the diagnosis of malignant tumors especially ovarian cancer.

PMID- 8758805
TI  - [Effects of assisted ovarian stimulation with leuprolide acetate on alterations
      of plasma estradiol levels and newly synthesized endometrial proteins].
AB  - OBJECTIVE: To evaluate the effects of leuprolide acetate (LA)-assisted ovarian
      stimulation on endometrial protein synthesis in hamsters. METHODS: Hamsters were
      treated separately with three different regimens: (1) 40 IU of pregnant mare's
      serum gonadotropin (PMSG) followed by 100 IU of hCG after 52 hours (PMSG alone
      group). (2) Same volumes of normal saline on the same schedule (control group).
      (3) 40 micrograms of LA daily prior to the same regimen of PMSG-hCG treatment in
      order to down-regulate the pituitary-ovarian functions (LA-PMSG group). The newly
      synthesized endometrial proteins were characterized and quantitated in vitro by
      3H-leucine incorporation test and 10% SDS-PAGE technique. RESULTS: The levels of
      newly synthesized 3H-labelled endometrial proteins were not different between LA
      PMSG and control groups. However, those of low and middle molecular weight (<
      31,000 and 45,000) proteins in the PMSG alone group were significantly lower than
      the levels in both LA-PMSG and control groups (P < 0.05, P < 0.01). CONCLUSIONS:
      The addition of LA in ovarian stimulation protocol resulted in more physiological
      endometrial protein synthesis. This phenomenon may causally related to higher
      pregnancy rate when applied in vitro fertilization-embryo transfer programs.

PMID- 8758807
TI  - [Uses of nitric oxide in obstetrics and gynecology].

PMID- 8758808
TI  - [Primary malignant lymphoma of corpus uteri].

PMID- 8758809
TI  - [Uterine papillary serous carcinoma--one kind of special type of uterine
      endometrial carcinoma].
AB  - OBJECTIVE: To study the clinico-pathologic features of uterine papillary serous
      carcinoma and point out the complete difference between the two kinds of
      endometrial carcinoma. METHODS: One hundred and ten cases of endometrial
      carcinoma who received treatment in the our hospital from May 1, 1982 to April
      30, 1994 were analyzed retrospectively. RESULTS: Of them, 10 cases (9.1%) of
      uterine papillary serous carcinoma (UPSC) were found. The age in average was 67.2
      years old, which is nearly 10 years older than those with ordinary endometrial
      cancer (P < 0.01). The occurrence of UPSC was revealed no relationship with the
      relative factors of occurrence of endometrial carcinoma. The study shows that
      tumor has very marked tendency of lymph node metastasis, much worse grade, much
      deeper myometrial invasion and much earlier extrauterine disease. CONCLUSIONS:
      UPSC is a special pathologic type of endometrial carcinoma with completely
      different clinico-pathologic behavior. The surgical staging is necessary for the
      patients with UPSC to get comprehensive stage because the clinical stage is
      usually not correct enough.

PMID- 8758810
TI  - [Uterine papillary serous carcinoma and papillary endometrial carcinoma: analysis
      of clinical biological behaviors of 56 cases].
AB  - OBJECTIVE: To characterize the clinical biological behavior and the pathological
      morphology of uterine papillary serous carcinoma and papillary endometrial
      carcinoma. METHODS: This is a retrospective analysis of 56 patients with
      papillary endometrial cancer treated at Cancer Hospital. Chinese Academy of
      Medical Sciences from January, 1981 to December, 1993. Of the 56 cases, 15 were
      uterine papillary serous carcinomas (UPSC), 41 papillary endometrial carcinomas
      (PEC). One hundred and sixty patients with endometrial adenocarcinoma (AC) were
      submitted as control group. RESULTS: 26.7% of UPSC, 14.6% of PEC and 5.6% of AC
      patients had stage III or IV by clinical examination (P < 0.05), whereas 53.3% of
      UPSC, 20.8% of PEC and 12.1% of AC patients has extrauterine disease at surgery
      (P < 0.01). Deep myometrial invasion occurred in 75.0% of UPSC, 41.7% of PEC, and
      32.3% of AC patients (P < 0.01). An increasing gradient of 5 year survival rate
      (life table method) was observed from UPSC (45.7%) to PEC (61.9%) to AC (90.3%)
      in their early stage (stage I-II) (P < 0.01). Upper abdominal spread was a common
      finding in UPSC which had a high rate of persistent disease (46.2%). The pelvis
      was the predominant involving site in PEC with a high frequency of recurrence and
      metastasis (31.0%). CONCLUSIONS: The presence of papillary features in
      endometrial carcinoma is an important prognostic indicator. The prognosis of PEC
      is better than UPSC, but worse than AC.

PMID- 8758811
TI  - [Analysis for 13 term deliveries after cardiac valve replacement and percutaneous
      transluminal mitral commissuroplasty].
AB  - OBJECTIVE: To study the cardiac function, mode of delivery and anticoagulant
      therapy in 13 pregnant women after cardiac valves replacement (CVR) and
      percutaneous transluminal mitral commissuroplasty (PTMC). METHOD: Retrospective
      data analysis. RESULTS: Patients with cardiac function of degree I to III can
      accomplish pregnancy and delivery safely after cardiac operation one and a half
      years. Using warfarin during pregnancy and delivery safely. Using warfarin during
      pregnancy and heparin during delivery did not increase the blood loss in both
      mothers and neonates, and congenital malformation either. It is more appropriate
      for pregnant women who had CVR to deliver by cesarean section and those who had
      PTMC to deliver vaginally. CONCLUSIONS: Women after cardiac operation can
      accomplish pregnancy and delivery if their cardiac function belong to degree I
      III with or without digoxin treatment before delivery. Using anticoagulant
      therapy correctly according to prothrombin time (PT) test during pregnancy does
      not increase delivery complications to both mothers and neonates.

PMID- 8758812
TI  - [The ananlysis of relationship between fetal stress and blood dynamics in fetal
      vessels and placental bed vessels].
AB  - OBJECTIVE: To evaluate the value of color Doppler ultrasound examination in
      perinatal monitoring. METHOD: Doppler ultrasound results of 22 cases with fetal
      stress and 6 cases with perinatal mortality were retrospectively analyzed, and
      compared that of 555 normal pregnancies with same gestational age (36 to 40
      weeks) using Ultramark 9 HDI color Doppler ultrasound. RESULTS: The resistance of
      fetal umbilical artery (FUA), fetal renal artery (FRA) and placental bed artery
      (PBA) in fetal stress group were significantly higher than that in normal
      pregnant group; there were no changes of resistance in middle cerebral artery
      (MCA). In perinatal mortality group, the resistance of FUA, FRA and PBA were the
      highest, the resistance of MCA was the lowest, and end-diastolic flow in FUA and
      FRA were absent or reverse. CONCLUSION: The results showed that fetal and
      placental flow dynamics study examined by color Doppler ultrasound is an
      effective method in the assessment of fetal well-being.

PMID- 8758813
TI  - [A prospective study on causal factors of female infertility with laparoscopy and
      transvaginal B-ultrasound].
AB  - OBJECTIVE: To study the casual factors of female infertility with laparoscopy and
      B-ultrasound. METHODS: Eighty-five infertile women were evaluated by serial
      transvaginal B-ultrasound scans for follicular development and ovulation and by
      laparoscopic examinations 2 to 6 days after ovulation. RESULTS: The patterns of
      follicular development and ovulation detected by B-ultrasound were: (1) ovulation
      from normal follicle (ONF) (56.47%); (2) ovulation from two follicles at the same
      time (O2F) (5.88%); (3) ovulation from small follicle (OSF) (16.47%); (4)
      ovulation from polycystic ovaries (PCO) (3.53%); (5) luteinized unruptured
      follicle syndrome (LUFS) (7.06%); (6) anovulation (10.90%). Laparoscopic
      examinations showed that the incidence of partial and complete tubal obstruction
      was 32.94% and pelvic adhesions 35.29%. Pelvic tuberculosis was found in 20.00%,
      which was the main disease leading to pelvic adhesions (46.67%), and tubal
      obstruction (60.71%). Endometriosis (EMS) was discovered in 36 cases (42.35%),
      among them, 30 (83.33%) had patent tubes. The stigmas or/and corpus hemorrhagica
      were seen in 60 out of 70 patients in whom ovulation had been diagnosed by B
      ultrasound. 6 cases were defined as "mechanically unruptured follicle syndrome".
      CONCLUSIONS: Abnormal follicular development may result in female infertility.
      Pelvic tuberculosis is another main causal factor of infertility. Endometriosis
      related infertility may rather result from other factors than tubal obstruction.
      Laparoscopic examinations combined with transvaginal B-ultrasound scans are very
      useful approaches in the etiological study of female infertility.

PMID- 8758814
TI  - [Autocrine transforming growth factor-beta stimulates human ovarian cancer cell
      growth in vitro and in vivo].
AB  - OBJECTIVES: Our previous studies have shown that human ovarian cancer cell lines
      COC1 and COC2 secrete transforming growth factor-beta (TGF-beta) like substance
      in serum-free culture. In this study the effect of COC1 and COC2-produced TGF
      beta like substance on COC1 and COC2 cell growth was investigated. METHODS: The
      COC1 and COC2 RPMI 1640 serum-free conditioned media SFCM (SFCM1 from COC1, SFCM2
      from COC2) were prepared, and their activities were investigated on COC1 and COC2
      cell growth (SFCM1 on COC1, SFCM2 on COC2) in vitro and in vivo, and compared
      with that of TGF-beta. RESULTS: SFCM1 and SFCM2 could separately promote COC1 and
      COC2 cell proliferation in culture with dose-dependent response, SFCM2
      significantly promoted COC2 cell growth in BABL/C nude mice. Radioreceptor assay
      showed that both COC1 and COC2 expressed TGF-beta receptor (or binding site). The
      above mentioned SFCM growth-stimulating effects can be partially blocked by anti
      TGF-beta antibody. CONCLUSION: The results suggest that there may be TGF-beta
      autocrine loop in the two ovarian cancer cell lines, which is associated with
      autonomous proliferation of COC1 and COC2 cells.

PMID- 8758815
TI  - [Enhancement of antitumor effect of cisplatin on human ovarian cancer by
      cyclosporin A in vitro and in vivo].
AB  - OBJECTIVES: To investigate the enhanced impact of cyclosporin A (CsA) on
      antitumor activity of cisplatin (DDP) for human ovarian cancer cells. METHODS: 
      IN VITRO STUDIES: human ovarian adenocarcinoma cells (COC1) and its resistant
      subline (COC1/DDP) were cultured separately with 4 different preparations: (1)
      normal saline; (2) CsA alone; (3) DDP alone; (4) DDP plus CsA. After 72 hours,
      the numbers of tumor cells were counted under microscope. Furthermore, 3H
      thymidine incorporation tests were performed on the above 4 systems, and the
      inhibitory rate of tumor growth were calculated. In vivo studies: normal saline
      or 2mg/kg of DDP and 5mg/kg of CsA was injected intraperitoneally to nude mice
      with COC1/DDP xenograft cancer every 3 day for 3 times. The changes of tumor
      volumes and its pathological appearances were compared before and after
      treatment. RESULTS: IN VITRO STUDIES, DDP combined with CsA exhibited a
      synergistic cytotoxic effect on COC1 and COC1/DDP cells. The decrease of tumor
      cell numbers reached 24%-36%, 48%-60% of controls respectively. The inhibitory
      rates of DNA synthesis of these tumor cells, measured by 3H-TdR incorporation
      tests, were greater in DDP plus CsA group than those in DDP alone group (64.7%
      63.9% versus 39.6% 25.1%, P < 0.01). The greater inhibitory rates of CsA+DDP
      regimen (81.4%) was also shown in vivo studies when compared with DDP alone
      regimen (49.1%) (P < 0.01). There were significant decreases of tumor cell
      density and nuclear mitosis in the combined group as compared with that of the
      DDP alone group (P < 0.01). CONCLUSIONS: The combination of DDP with 2
      micrograms/ml of CsA yields enhancement of antitumor effect on human ovarian
      cancer. This study suggests that CsA may be used clinically as an antitumor
      enhancement of DDP for the treatment of ovarian adenocarcinoma.

PMID- 8758816
TI  - [Comparative study on assessment of tubal patency among tubal insufflation,
      hydrotubation, hysterosalpingography and chromotubation under laparoscopy].
AB  - OBJECTIVES: To compare the diagnostic value of tubal insufflation, hydrotubation,
      hysterosalpingography (HSG) and chromotubation under laparoscopy for tubal
      patency assessment. METHODS: Among 258 women who underwent chromofubation during
      laparoscopy procedures for infertility assessment in our hospital, tubal
      insufflation were performed in 42 cases, hydrotubation in 70, HSG in 63, both
      insufflation and hydrotubation in 20, insufflation and HSG in 11, and
      hydrotubation and HSG in 22. The accuracy of each method was compared with that
      of chromotubation under laparoscopy. RESULTS: The accuracy rates of hydrotubation
      (87.1%) and HSG (73.0%) were significantly higher than that of insufflation
      (50.0%) (P < 0.01, P < 0.05 respectively). Similar results were shown when 2
      different procedures in the same patient were compared with laparoscopy.
      CONCLUSIONS: Tubal insufflation has no longer its place in tubal patency
      assessment due to its grossly inaccuracy; Both hydrotubation and HSG can be used
      as screening methods. Laparoscopy is the most accurate procedure in assessing
      tubal patency, as well as in searching pelvic abnormalities.

PMID- 8758817
TI  - [Serious papillary endometrial adenocarcinoma].

PMID- 8758818
TI  - [The role of nitric oxide in the pathogenesis of pregnancy induced hypertension].

PMID- 8758819
TI  - [Clinical study and application of auricular magnet anesthesia for the operation
      of the thyroid].

PMID- 8758820
TI  - [Afferent projections to the central superior raphe nucleus of brain stem and its
      relation to acupuncture anesthesia].
AB  - The afferent projections to the central superior raphe nuclus (CS) in the rat
      were investigated by means of HRP retrograte tracing method. 3% WGA-HRP 0.05-0.1
      microliters was injected into the CS in each of 11 rats. The labeled cells were
      found in the medial part of lateral habenular nucleus, posterior hypothalamic
      area, lateral subnucleus of interpeduncular nucleus, dorsal raphe nucleus,
      periaqueductal gray matter, dorsal paramedial nucleus, preposital hypoglossal
      nucleus, dorsal paragiganto-cellular nucleus, magnum raphe nucleus, and
      fastigatum of cerebellum. The results provide morphological basis for researching
      function of the CS in acupuncture anesthesia.

PMID- 8758821
TI  - [The effect of intrathecal injection of neurotensin on acupuncture analgesia in
      rats].
AB  - The influence of intrathecal injection of Neurotensin (NT) and Anti-NT serum
      (ANTS) on pain threshold, and electroacupuncture (EA) analgesia in the rat was
      investigated. The tail-flick induced by potassium iontophoresis was used to
      measure the pain threshold. The increase of pain threshold was observed within
      100 min, after NT injection (2 micrograms), and it was more effective than that
      of the ACSF injection (P < 0.01). The NT administration could also enhance the EA
      analgesia. On the contrary, the pain threshold was decreased in ANTS group as
      compared with that of ACSF control group. The ANTS administration could decreased
      the role of EA analgesia. Our data show that NT in spinal cord may play an
      important role in the EA analgesia.

PMID- 8758822
TI  - [Influence of microiontophoretic morphine on nociceptive responses of Pf neurons
      after lesion of SmI].
AB  - Neuronal responses in thalamic nucleus parafasciculus (Pf) to microiontophoretic
      morphine were examined in 20 wistar rats after lesion of SmI. Extracellular
      recordings were made with five-barreled glass microelectrodes. The results showed
      that the spontaneous responses of Pf neurons were not statistically changed (n =
      11, P > 0.05), but their nociceptive responses were attenuated at 0-8 minutes
      after iontophoretic morphine (n = 11, P < 0.05). There were statistically
      significant differences in nociceptive responses between morphine and saline
      groups at 0-8 minutes after iontophoresis. The results suggest that morphine may
      be involved in corticofugal modulation of nociceptive responses in thalamic Pf
      neurons.

PMID- 8758823
TI  - [Effect of brain somatostatin on electroacupuncture analgesia of rat].
AB  - The purpose of this study was to verify the role of somatostatin (Som) of brain
      in analgesia of electroacupuncture (EA). Intracerebroventricular (icv) injection
      of Som caused a more marked elevation of pain threshold and of EA analgesic
      effect, but the activity of Ca(2+)-APTase in hippocampus was significantly
      decreased; The Som and GABA levels in hippocampus and brain stem were decreased
      by EA analgesia. The Som in hippocampus and brain stem were obviously depleted by
      icv injection of cycteamine, but without any change of pain threshold and
      analgesic effect of EA. These results indicated that the exogenous Som of brain
      potentiated the analgesic effect of EA, however, the decrease of endogenous of
      some brain regions took part in the process of EA analgesia.

PMID- 8758824
TI  - [Effects of electroacupuncture at different time on brain methionine-enkephalin
      contents in rats].
AB  - The basic level of methionine-enkephalin (MEK) in rat medulla oblongata plus pons
      was the highest at 05:00 o'clock and the lowest at 23:00. In both the
      hypothalamus and the striatum at 05:00 MEK levels were respectively higher than
      those at 11:00, 17:00 amd 23:00. In both the hippocampus and the midbrain at
      05:00 and 23:00 they were respectively higher than those at 11:00 and 17:00. In
      the cortex it was higher at 05:00 than those at 11:00 and 17:00.
      Electroacupuncture (EA) at 05:00 increased the MEK content in the medulla
      oblongata plus pons and decreased the MEK content in the hypothalamus. EA at
      11:00 produced decreases of MEK concentrations in the medulla oblongata plus pons
      and the midbrain and increases of MEK content in the cortex. At 17:00 it
      increased the MEK level in the hypothalamus and at 23:00 it reduced the level of
      MEK in the hippocampus. The results suggest that there are very marked circadian
      rhythms in the MEK basic levels of the six discrete brain regions observed and EA
      at different hours produces different effects on brain MEK levels.

PMID- 8758825
TI  - [The functional connection among the "zusanli"-spinal dorsal horn neurons
      trigeminal sensory nucleus of rats].
AB  - Electrical stimulation of Zusanli (ST36) point and Trigeminal Sensory Nucleus
      (TSN) as well as microelectrode recording from the laminae II - VI of the lumbar
      spinal dorsal horn have been used on the pentobarbital anesthetized rats, finding
      and identifying 142 spinal neurons responding to the stimulation of both ST36 and
      TSN. Among them, 29 responded antidromically to TSN; the others, responded
      orthodromically to TSN; These neurons distributed in the L2-S1 segments, the most
      in the L3-L6 segments, and in the laminae III-V, occasionally in the laminae II
      and VI in the spinal dorsal horn, the LTM and WDR neurons were 50% respectively
      of them. The results indicate that (i) single spinal dorsal horn neurons receives
      ST36 afferent input and then conveys it to the TSN; (ii) some spinal dorsal horn
      neurons receive, in turn, innervation from TSN; (iii) The convergence and
      integration between ST36 and TSN inputs might occur in the spinal dorsal horn
      neurons.

PMID- 8758826
TI  - [Effect of acupuncture on the contents of enkephalins in different brain regions
      of rats with traumatic shock].
AB  - The study was carried out on the animal model of traumatic shock which induced by
      ligating bilateral hind legs. The contents of enkephalins in hippocampus,
      striatum, hypothalamus, diencephalon and brain stem were determined with
      radioimmunoassay. The results show that: (1) when traumatic shock occurs, the
      contents of Met-enkephalin are not obvious change in the above 5 brain regions,
      and also not significant change after acupuncture; (2) there is a tendency to
      increase the content of Leu-enkephalin in each brain region described above of
      shock animal, while it is decreased in hypothalamus after acupuncture. The result
      suggests that the occurrence of traumatic shock may be related to the functional
      activities of Leu-enkephalinergic system in the central nervous system; the anti
      shock of acupuncture may be through a decrease in the level of central Leu
      enkephalin to improve micro-circulation and raise the blood pressure.

PMID- 8758827
TI  - [Histochemical observation of the effect of electroacupuncture on the livers of
      rats with endotoxic shock].
AB  - The experimental rats were randomly divided into three groups: i.e. control
      group; endotoxic shock group (the model of endotoxic shock was induced by
      intravenous administration of E. Coli endotoxin, 16 mg/kg); and
      electroacupuncture (EA) group ("Renzhong" or "Zusanli" acupoint was stimulated
      for 15 minutes at 1 hr after injection of endotoxin). The experimental rats were
      decapitated at 75 minutes after injecting endotoxin. Their livers were taken out
      for cryostat section, and histochemical observation. The results were as follows:
      1) The glycogen in the hepatic cells of endotoxic shocked rats were almost
      completely depleted. The activities of SDH Mg(++)-ATPase and G-6-Pase and 5'-Nase
      were decreased; especially the activities of 5'-Nase in the biliary canaliculi
      and sinusoids were apparently reduced. 2) The content of hepatic glycogen in EA
      group was increased, but some of them was still depleted. The activities of SDH,
      Mg(++)-ATPase and G-6-Pase were slightly increased as compared with that of the
      endotoxic shock group. The activity of 5'-Nase was obviously increased after EA.
      The preliminary results indicated that EA at "Renzhong" or "Zusanli" acupoint of
      rats with endotoxic shock might play certain role on improving the hepatic
      metabolism and promoting the membrane transport action.

PMID- 8758828
TI  - [Clinical and experimental researches in the inhibition of bile pigment
      lithogenesis by acupuncture and moxibustion].
AB  - Clinical subjects were the patients in whom cholecystectomy and choledochotomy
      were performed with T tube drainage. Four groups of acupoints were established
      according to different point prescriptions. Under the strict control of
      experimental conditions and fixation of electrical acupuncture stimulation
      parameters, the changes of hepatic bile output were observed in five different
      stages before, during and after acupuncture, and compared with those in control
      group not treated by acupuncture. The results showed that electrical acupuncture
      of Ganshu (Back-Shu point) (GB 18) and Qimen (Front-Mu point) (LI 14) could
      obviously promote the secretion of hepatic bile. The immediate effect was
      superior to that in other groups. In a group not treated by acupuncture, hepatic
      bile output gradually decreased as time went on. In animal experiment, a model of
      bile pigment lithogenesis was made in guinea pig. The animals were randomly
      divided into five groups of control, simultaneous acupuncture, simultaneous
      moxibustion, re-acupuncture after one week and re-acupuncture after two weeks.
      The results indicated that electrical acupuncture or moxibustion of relevant
      acupoints such as Ganshu (GB 18) and Qimen (LI 14) could really very effectively
      inhibit the animal lithogenesis caused by lithogenesis food. A tendency was
      observed towards that the earlier acupuncture was performed, the better the
      preventive effect on lithogenesis. In the influence on lithogenesis bile, both
      acupuncture and moxibustion could reduce the contents of biliary total bilirubin
      and free bilirubin and the activity of biliary beta-glucuronidase. Acupuncture
      also produced an effect in lowering hepatic beta-glucuronidase but moxibustion
      didn't. Hepatohistological observation showed that lithogenous food could also
      cause fatty degeneration of liver, and moxibustion could markedly inhibit its
      progress. Both acupuncture and moxibustion didn't remarkably influence the
      content of serum cholesterol.

PMID- 8758829
TI  - [Effects of electroacupuncture on gastrin, mast cell and gastric mucosal barrier
      in the course of protecting rat stress peptic ulcer].
AB  - The experimental Wistar rats were divided into two groups, the acupuncture group
      and the control group. Stress-induced gastric ulcer models were established by
      immersion of restrained rats in water. The electroacupuncture was able to protect
      stress rat from stress induced peptic ulcer. The results indicated that
      electroacupuncture protecting rat from stress ulceration was relevant to
      enhancing gastric mucosal barrier, stabilizing gastric mast cell and inhibiting
      the gastrin levels in gastric mucous.

PMID- 8758830
TI  - [Changes of amino acids release in rat's hippocampus during kainic acid induced
      epilepsy and acupuncture].
AB  - Changes of amino acids release in rat's hippocampus were studied by using push
      pull perfusion and high performance liquid chromatography (HPLC) with
      fluorometric detection techniques during kainic acid (KA) induced epilepsy and
      acupuncture. The results indicated that the levels of glutamate, aspartate,
      glycine and GABA were statistically increased in hippocampus 40min after
      administration of KA. After EA treatment, there was marked elevation in the
      extracellular level of taurine. It's shown that the inhibitory effect of EA on
      epilepsy may be related to the increase of inhibitory amino acids's release in
      hippocampus.

PMID- 8758831
TI  - [Influence of acupuncture on blood pressure, contents of NE, DA and 5-HT of SHR
      and the interrelation between blood pressure and whole blood viscosity].
AB  - Twenty spontaneous hypertensive rats (SHR) with systolic blood pressure (SBP)
      >or= 20 kPa were chosen and divided randomly into two groups (acupuncture group
      and control group). The former was acupunctured on bilateral Quchi (L1 11),
      Zusanli (ST 36). Another 46 immature SHRs which were about 7-week-old with SBP
      ranged from 16 kPa to 20 kPa were given 10% high molecular weight dextran (HMWD)
      or normal saline by intervention respectively. The results showed: 1. After three
      course of acupuncture, SHRs' SBP dropped remarkably from 25.493 +/- 0.73 kPa to
      19.547 +/- 0.555 kPa (P < 0.01); 2. After three courses of acupuncture, NE and 5
      HT contents in plasma were lowered (P < 0.05, < 0.01) and DA content in plasma
      was increased (P < 0.05) compared with that in the control group. 3. After three
      course of acupuncture, NE content in brainstem, hypothalamus, cerebral cortex
      increased (P < 0.005-0.01) and DA content in brainstem, cerebral cortex increased
      remarkably (P < 0.005-0.01) compared with that in the control group. 5-HT content
      in brainstem, hypothalamus, and cerebral cortex increased obviously compared with
      that in the control group. 4. After 1 or 2 hours of intervention of 10% HMWD to
      immature SHR, the whole blood viscosity and blood pressure rise remarkably
      compared with normal saline group. The experiment implies that the mechanism of
      lowering the blood pressure of SHR by acupuncture lies in that it can adjust NE,
      DA and 5-HT contents in plasma and central nervous system to adjust the activity
      of sympathetic, reduce whole blood viscosity etc.

PMID- 8758832
TI  - [Treatment of ototoxic auditory damage caused by kanamycin with
      electroacupuncture at different acupoints].
AB  - We adopted the technique and method of integrating the morphology with function
      to select the effective acupoints for treatment of deafness. The results show
      that: (1) Tinggong (SI 19), Yifeng (TE 17), Waiguan (TE 5), Shenshu (UB 23),
      Sanyinjiao (SP 6) and Zhubin (KI 9) etc. are the effectine acupoints for the
      treatment of ototoxic auditory damage caused by drug, especially, the effect of
      Tinggong, Sanyinjiao and Zhubin etc, is much better; (2) electroacupuncture can
      promote audibility, improve SDH activity and relieve progressing injury of
      auditory hair cells, (3) FFR method has an important significance in the
      determination of ototoxic damage caused by drug.

PMID- 8758833
TI  - [Effect of acupuncture on the regulation of cell-mediated immunity in the
      patients with malignant tumors].
AB  - In order to investigate the role of acupuncture in the regulation of cellular
      immune function, we observed acupuncture therapy affecting the levels of T
      lymphocytes subgroup (CD3+, CD4+, CD8+), soluble interleukin-2 receptor (SIL-2R)
      and beta-endorphin (beta-EP) in the peripheral blood of patients with malignant
      tumors. Here was used the random-gioland method, the patients were divided into a
      group treated by acupuncture (acup. group, 20 cases) and a control group (20
      cases). The acup. group was treated using points PC6, LI4, ST36, RN4 and location
      of symptomatic points bilaterally, one treatment of 30 min daily for 10 days. The
      results showed that there were increased levels of CD3+, CD4+ percentage,
      CD4+/CD8+ ratio and radioimmunoassay of beta-EP in blood plasma, a decreased
      level of SIL-2R after acup. The statistical significance was found to be
      remarkable (P < 0.01), so has a notable difference, the correlation analysis
      indicated: (1) there was a positive correlation between beta-EP and T-lymphocytes
      subgroups; (2) a negative correlation between beta-Bp and SIL-2R, so did it
      between T subgroups and SIL-2R. Our results showed that beta-EP enhanced immune
      function of patients by increased T lymphocyte subgroups, reduced SIL-2R, and
      this action of beta-EP may be mediated by opioid receptor. The above mentioned
      results prevented evidence that there was an adjusting-network of immune in the
      body, through this way, acup. therapy can heighten the cellular immune function
      of patients, providing a beneficial effect in anti-cancer treatment.

PMID- 8758834
TI  - mRNA expression of vimentin gene in lens of transgenic mouse and DNA
      amplification in human cataracts.
AB  - PURPOSE: To investigate the role of vimentin gene in cataractogenesis. METHODS:
      The 12.7kb chicken vimentin genes were microinjected into the male pronuclei of
      918 fertilized mice eggs. 841 injected embryos were transferred into oviducts of
      pseudopregnant recipient females, of which 12 pregnant mice gave birth to 49
      offspring mice. The integration and expression of exogenous gene in the offspring
      were analysed by Southern and Northern blot hybridizations. In the human senile
      cataract, the lens vimentin gene was analyzed with the chicken vimentin gene
      probe. RESULTS: It showed that four of F1 offspring were transgenic mice in which
      the chicken vimentin gene was integrated in their genomes. The transgenic band
      was 12kb, similar to the 12.7kb chicken vimentin fragment injected. One 2kb
      vimentin mRNA was visualized on E2 mouse lens blot, which revealed that the
      chicken vimentin gene was efficiently expressed in this transgenic mouse. In the
      human senile cataract lens, 12kb BamHI-restricted vimentin fragments displayed a
      stronger hybridization signal than that of the control lens in Southern blot
      analysis. It implies that the formation of human senile cataract may be
      associated with the amplification of vimentin gene. CONCLUSIONS: We have
      successfully developed four transgenic mice bearing chicken vimentin gene and
      having mRNA expression which can be used for further study. It is to be observed
      if the normal lens cell function is affected by the expressed product and
      cataract occurs in our transgenic mice. The cause of the gene amplification in
      human cataract remains for further investigation.

PMID- 8758835
TI  - A study on HSV-1 corneal potential infection by in situ nucleic acid
      hybridization.
AB  - PURPOSE: To evaluate the possibility of HSV-1 corneal latency by in situ nucleic
      acid hybridization in animal models. METHODS: 20 normal New Zealand White (NEW)
      rabbits were used, 14 of them were inoculated bilaterally with 3 x 10 PFU/ml of
      McKrae strain HSV-1 by intrastromal injection. 22/28 eyes developed typical
      herpes simplex keratitis (HSK) diseases. At 60 day postoperation (PI), 4 latent
      corneas were transplanted to one eye of 4 noninfected NZW rabbits and removed 2
      weeks PI. Corneas at all time intervals of infection and two weeks after PKP were
      detected for presence of HSV-1 antigen and nucleic acid sequences by using clonal
      IgG HSV-1 antibody and biotinylated HSV-1 DNA probe individually. RESULTS: The
      results showed that the HSV-1 DNA sequences were retained within the corneal
      epithelium and anterior stromal keratocytes during acute diseases, while the
      corneas during latent infection and postoperation, the HSV-1 DNA sequences were
      retained only within the stromal layer with negative HSV-1 antigen staining.
      CONCLUSIONS: These results strongly suggest that the cornea may be capable of
      harboring latent HSV-1.

PMID- 8758836
TI  - Lymphocyte proliferation response to S antigen in patients with uveitis and optic
      neuritis.
AB  - PURPOSE: To evaluate the autoimmunity which may play a major role in the etiology
      of certain forms of uveitis and optic neuritis. METHODS: Lymphocyte proliferation
      response to retinal soluble antigen in vitro by incorporation 3H-thymidine with
      DNA was tested in 115 patients with anterior uveitis, posterior/pan-uveitis,
      optic neuritis, and 50 volunteers with unrelated diseases such as congenital
      ptosis, strabismus, or completely healthy persons as control. RESULTS: The
      positive rate of lymphocyte stimulation was 34% (18/53) in anterior uveitis,
      41.5% (17/41) in posterior/pan-uveitis, and 57.1% (12/21) in optic neuritis. The
      results in the experimental groups were significantly different from those of the
      control group (X2 = 14.76, P < 0.05, x2 = 19.14, P < 0.005, x2 = 26.38, P <
      0.005, respectively). CONCLUSION: The autoimmunity plays a role in the
      pathogenesis in certain forms of uveitis and optic neuritis. Such immune
      responses may be secondary to the exposition or release of retinal antigens by
      various causes, leading to activation or augmentation of meager or low-affinity S
      antigen specific lymphocytes which may pre-exist in the circulation and starting
      the pathogenic autoimmune process.

PMID- 8758837
TI  - Change of water-soluble-protein, urea-soluble-protein and membrane intrinsic
      protein in human senile cataract.
AB  - PURPOSE: To analyze the change of water-soluble-protein (WSP), urea-soluble
      protein (USP) and membrane intrinsic protein (MIP) in human senile cataract.
      METHODS: The water-soluble-fractions (WSF) were prepared basically according to
      the method of Kibbelear, et al. But in this study, 5 mmol/L B-mercaptoethanol was
      added to the buffer solution. The urea-soluble-fractions (USF) were prepared
      basically according to the method of Kibbelear, et al. Lens fiber cell membranes
      were purified basically according to the method of Russell, et al. SDS-PAGE were
      performed according to the procedure of Laemmili, et al. using resolving gel 13%
      and 3% stacking gel. RESULTS: The WSP was fractionated into HM+ alpha-, beta(1-3)
      and gamma-crystallin components. In nuclear cataractous lenses HM+ alpha- and B
      crystallin increase, while r-crystallin decrease. The USP from clear lenses
      contains mainly alpha beta chains of 22KD, whereas in cataractous lenses,
      especially in nuclear cataractous lenses, the relative amount of the 28- and 23KD
      polypeptide (the components of beta-crystallin) increased markedly. Lens fiber
      cell MIP, clear lens and cataract lens contained the main polypeptide of 27KD
      (MIP) and 23KD (MP23). CONCLUSION: The water-insoluble protein, whether in
      quantity or in quality, plays an important role in cataract formation.

PMID- 8758838
TI  - Nd: YAG laser lysis of the fibrinous membrane and remnant substance on the
      anterior surface of intraocular lens.
AB  - PURPOSE: To determine the effects of Nd: YAG laser to disrupt the fibrinous
      membrane and remnant substance on the anterior surface of intraocular lens.
      METHODS: Nd: YAG laser was applied on 23 cases of fibrinous membrane formation
      and 8 cases of remnant substance on the anterior surface of intraocular lenses
      (IOL) which had not responded well to steroid therapy. Eighteen cases were male
      and 13 female. The mean age was 49.7 years (range, 5 approximately 78 years). The
      interval between IOL implantation and laser therapy was 0.5 approximately 30
      months in the fibrinous membrane cases and 3 approximately 10 days in the remnant
      substance cases. The energy applied was 0.8 approximately 3.0 mJ/exp. with 2
      approximately 112 exposures. Mean follow-up period was 3.6 months. RESULTS:
      Complications during therapy included only 2 cases of slight iris bleeding.
      Visual acuity after therapy was improved 1 line in 16 cases, 2 lines in 11 cases,
      3 lines in 1 case, 4 lines in 1 case and 5 lines in 2 cases. No post-therapy
      complication was found. CONCLUSIONS: Nd: YAG laser lysis is an effective
      alternative to remove the fibrinous membrane and remnant substances on the
      anterior surface of IOL.

PMID- 8758839
TI  - Membrane formation on the surface of implanted posterior chamber intraocular
      lenses.
AB  - PURPOSE: To study the prevention and treatment of the membrane formation on the
      lens surface after extracapsular cataract extraction (ECCE) with posterior
      chamber intraocular lens (PCIOL) implantation. METHODS: We reviewed the records
      of 312 cataractous patients that had undergone ECCE with PCIOL implantation
      between 1989 and 1993. Postoperatively all patients were examined under slit-lamp
      microscopy. The membrane formation on the surface of PCIOL in pupilar area was
      divided into four grades. Two membranes of surgical removal were observed under a
      transmission electron microscopy. One PCIOL of surgical removal was observed
      under a scanning electron microscopy. RESULTS: Of 312 patients, 21 had the
      membrane formation on the surface of the PCIOL postoperatively. The incidence of
      the membrane formation was 6.7%. Comparisons with cases of senile cataract showed
      the incidence to be significantly the highest among: 1. patients who had
      traumatic cataract (P < 0.05); 2. patients with complicated cataract (P < 0.05).
      Intraoperatively residual lens cortex and rupture of posterior capsule, interval
      time between the first and second eye operations less than 1 month are the main
      factors of membrane formation. The ultrastructure in membrane and cytology on the
      lens surface showed that the membrane on the surface of PCIOLs is usually
      composed of a cellular protein film and cellular elements, including macrophages,
      fibroblast-like cells, epithelioid cells, giant cells, fibroblasts and collagen
      fibrils, etc. CONCLUSIONS: The cellular response on the surface of an implanted
      PCIOL is a chronic foreign-body inflammatory reaction and the membrane of the
      surface of implanted PCIOL is a reactive membrane of the foreign-body.

PMID- 8758840
TI  - Modified scleral flap incision to reduce corneal astigmatism after intraocular
      lens implantation.
AB  - PURPOSE: To investigate a simple method during extracapsular cataract extraction
      with posterior chamber intraocular lens implantation in order to reduce
      surgically induced corneal astigmatism. METHODS: A modified scleral flap incision
      was used in the extracapsular cataract extraction with intraocular lens
      implantation and the postoperative changes in corneal astigmatism was observed.
      RESULTS: The peak value of postoperative corneal astigmatism was 3.60 D, and the
      corneal astigmatism regression was 2.11 D, surgically induced astigmatism was
      less significant in modified scleral flap incision group than that in
      conventional limbal incision group (P < 0.05). CONCLUSIONS: The modified scleral
      flap incision is an ideal incision for cataract extraction with intraocular lens
      implantation when phacoemulsifier is not available.

PMID- 8758841
TI  - Primary posterior chamber intraocular lens implantation in traumatic cataract
      with posterior capsule breaks.
AB  - BACKGROUND: In patients with incomplete posterior capsule support, posterior
      chamber intraocular lenses (PC-IOLs) were implanted with both haptics
      transscleral fixation. This causes more damage to the eye and may result in more
      complications. In patients with small posterior breaks, non-fixation or single
      haptic fixation may be adequate. METHODS: Thirty-two consecutive patients of
      traumatic cataract with posterior capsule breaks caused by penetrating eye trauma
      were retrospected. Posterior chamber intraocular lenses were implanted in all
      these patients with three techniques, ie, without fixation, with single haptic
      fixation and with both haptics fixation. The selection of the technique was based
      on the position and size of the posterior capsule. The follow-up period was 21
      days to 28 months (mean, 15.2 months). RESULTS: Intra-operative problems included
      ciliary body bleeding (two patients, 6.25%) and enlargement of posterior capsule
      breaks (2 patients, 6.25%). Postoperative visual acuity was 0.5 or better
      (corrected) in 28 case (87.5%) and 0.1-0.4 in four patients (12.5%).
      Postoperative complications included hyphema (6 eyes, 18.8%), transient
      intraocular pressure elevation (6 eyes, 18.8%), transient hypotention (7 eyes,
      21.8%). Postoperative IOL position were good except one case of IOL tilt. No
      pupillary capture or endophthalmitis was found. CONCLUSIONS: Not all PC-IOLs have
      to be fixed by two haptics. In patients with small posterior capsule breaks, PC
      IOL may not be fixed or fixed by only one haptics.

PMID- 8758842
TI  - Laser Raman spectrometry study on experimental galactose-induced cataract.
AB  - PURPOSE: To observe the dynamic changes of hydration in galactose induced
      cataract. METHODS: Two groups of Wistar rats were used in the experiment. There
      were 12 rats in the experimental group, which were fed diet of 50% D-Galactose
      standard feed; while the control group had 8 rats fed standard feed. Their other
      living conditions were the same. At desired time periods, two Wistar rats fed
      galactose and one normal control were selected and killed 20 minutes before the
      instrument examination respectively, then, their lenses were removed from the
      orbs by a posterior approach. The cleaned fresh lens was placed in a quartz
      cuvette with Tris buffered balanced salt solution containing 5.5 mmol/L glucose.
      The quartz cuvette was placed on the stage of the Spectrometer. The laser beam
      was focused at the lens nuclear from the bottom of the cuvette and the scattered
      light was collected at 90 degrees to the incident beam. RESULTS: Raman
      spectroscopy showed that (1) during the formation of galactose cataract, the
      water signal (at 3390cm-1) increased obviously, and the ratio of I3390/I2935
      increased from 0.31 (3 days) to 2.26 (17 days), which is correlated with the
      imbibition of water in the lens nuclear; (2) the hydration of lens nuclear could
      be divided into two phases. The ratio I3390/I2935 was increased slowly and
      steadily by 11 days after galactose feeding. Then, the ratio turned to increase
      quite fast till 17 days. CONCLUSION: The hydration of nuclear is changed
      simultaneously with the formation of cataract. The hydration of nuclear is mainly
      due to the imbalance of Na+/K+.

PMID- 8758843
TI  - A study on the structure of human optic nerve lamina cribrosa.
AB  - PURPOSE: To determine the mechanism of nerve fiber damage in glaucoma by studying
      the structure of human optic nerve lamina cribrosa (LC) in different regions.
      METHODS: 15 human eyes of 10 cases were studied. The specimens were prepared for
      scanning electron microscopy, and numbers and areas of pores in LC were measured
      by electron image analysis system. Draw a frequency distribution map with each
      curve represents the tendency of pores distribution in a particular part. The
      proportion of the connective tissue in respective quadrant can also be
      calculated. The specimens were also prepared for histological examination.
      RESULTS: There are many pores of various magnitude and shapes on the surface of
      LC. There are significantly more large pores (> or = 3000 micron2) in the
      superior and inferior than those in the nasal and temporal quadrants, especially
      in the peripheral regions. In terms of area, the percentages of connective tissue
      in the nasal and temporal quadrants are the highest. Collageous fibers, various
      in diameter, are arranged in bundles and tangentially around each pore.
      CONCLUSION: In normal persons, the percentage of large pores in the superior and
      inferior peripheral parts is the highest, the density of the connective tissue is
      the lowest. So, the force received by unit area of the superior and inferior
      parts is bigger than that of the nasal and temporal sides, therefore, it is
      susceptible to the impact of high intraocular pressure at the early stage and
      causing corresponding visual defect. Our study may suggest the mechanism of optic
      nerve damage of glaucoma.

PMID- 8758844
TI  - Characteristics of reversal optic cupping in adults glaucoma after reduction of
      intraocular pressure.
AB  - PURPOSE: According to Quigley's hypothesis the dense of connective tissue is the
      least and the pores of the lamina cribrosa are the largest at the superior and
      inferior poles of the lamina cribrosa, therefore they are the most vulnerable
      location to be involved in the characteristic glaucomatous optic nerve damage. To
      get clinical evidence for the hypothesis, the reversal of optic cup in adults
      glaucoma after reduction of intraocular pressure (IOP) was examined. METHODS: The
      stereoscopic flicker comparison on with computerized image system was used to
      monitor the optic cup's changing, 2 serial superposed stereo pairs were displayed
      alternatively and rapidly and the changing parts appeared moving Under the
      stereoscopic observation, the changes of 3-dimension optic cup could be seen and
      the false positive phenomena caused by photographic angle variation, vascular
      pulsation could be differentiated from the characteristic change of the cup.
      Stereo fundus photographs were taken from 31 eyes with hypertension glaucoma
      before and after treatment of reduction of IOPs which was either diamox
      administration or trabeculectomy. RESULTS: The result showed that the reversal of
      optic cups after reduction of IOPs were mostly asymmetrical, especially at the
      inferior and/or superior poles. By multiple stepwise regression, it is known that
      the amount of the change is only correlated with the initial elevated IOP.
      CONCLUSIONS: The study indicated that it was the distortion and deformity of the
      lamina cribrosa leading to shearing stress that results in glaucomatous
      characteristic damage in structure and function. The individual tolerance of the
      lamina cribrosa to the high intraocular pressure and the locations of individual
      vulnerable at the optic nerve head are various.

PMID- 8758845
TI  - The changes of pattern reversal visual evoked potentials in normal infants.
AB  - PURPOSE: To study pattern reversal visual evoked potential (PVEPs) and determine
      the developmental character and mature time of visual function in normal infants
      at different months of age. METHODS: PVEPs were recorded from 115 normal infants
      at 3, 6, 9, 12 months age. P1 latency for different checks (1 degree 40', 25',
      6') was analyzed and compared to those of normal adults. Changes of N1, N2
      latency of PVEPs were also examined. RESULTS: P1 latency for all checks (1 degree
      40', 25', 6') was significantly longer at 3 months than at 6 months of age (P <
      0.05), but no significant differences can be seen after 6 months of age for
      larger (1 degree 40') and intermediate (25') checks (P > 0.05). P1 latency for
      larger checks (1 degree 40') reached adult level after 3 months of age, but not
      for the intermediate check (25'), while P1 latency for small check (6') presented
      the character of fluctuation. CONCLUSION: The visual system continued to develop
      after birth and appeared a certain regularity. Our results showed that P1 latency
      for larger check (1 degree 40') reached adult levels after 3 months of age. But
      P1 latency for intermediate check still has not reached adult levels after 3
      months of age. To determine the age at which adult levels are finally reached,
      infants of 12 months and older must be tested. The reason why P1 latency for
      smaller check (6') presented the character of fluctuation should be the temporal
      tuning function developing much more slowly.

PMID- 8758846
TI  - The retinal nerve fiber layer defects in patients with anterior ischemic optic
      neuropathy.
AB  - PURPOSE: To demonstrate the effects of optic nerve ischemia on retinal nerve
      fiber layer (RNFL) and the associated visual dysfunction. METHODS: 23 patients
      (25 eyes) with anterior ischemic optic neuropathy (AION) underwent fundus
      fluorescein angiography (FFA), and then red-free light pictures were taken via SE
      40 exceiter filter. All pictures were printed for RNFL analysis. Humphrey central
      field analysis was conducted. All data obtained from FFA and visual field defects
      were analysed statistically. RESULTS: The RNFL defects and the corresponding
      visual field defects were presented in 23 of 25 eyes (92%). The optic disc
      filling defects, RNFL defects and visual field defects were found to be highly
      correspondent to each other. The RNFL defects were mainly the local losses of
      RNFL which were correspondent to the ischemic regions. CONCLUSION: The poor optic
      disc filling or ischemia can result in the RNFL defects which cause the
      associated visual dysfunction. Because RNFL defects are irreversible changes, the
      potential values in predicting the prognosis of visual field defects caused by
      RNFL damages were suggested.

PMID- 8758847
TI  - Effect of the multiglycoside of Tripterygium Wilfordii Hook f. (Tii) on cornea
      allograft rejection model in rabbit.
AB  - PURPOSE: To examine the effect of Tii treatment of cornea graft survival in a
      rabbit model. METHODS: Tii was administered orally after eccentrical corneal
      transplantation. Survival times were determined by biomicroscopy. Cytotoxic T
      lymphocytes (CTL) and delayed-type hypersensitivity (DTH) responses to donor
      alloantigens were assessed at day 16 after heterotopic corneal grafts. RESULTS:
      Administration of Tii reduced the incidence and prolonged the graft survival
      time. Both CTL and DTH responses to donor alloantigens were severely depressed in
      hosts treated with Tii. However, combination of Tii and cyclosporine further
      enhanced the immunosuppressive effects described above. CONCLUSIONS: Tii is a
      potent immunosuppressant with the ability to prolong allograft survival in the
      rabbit penetrating keratoplasty model and may have coordinative effects with CsA
      through different mechanisms. Further studies are necessary to define any
      potentially coordinative role in the prevention of allograft rejection in human
      keratoplasty.

PMID- 8758848
TI  - Experimental studies of the effect of Forskolin on the lowering of intraocular
      pressure.
AB  - PURPOSE: To determine the effect of domestic Forskolin on lowering of intraocular
      pressure (IOP) in rabbits. METHODS: Measure the normal IOP and ocular
      hypertension by water load in rabbits using Perkins tonometer. Measure the
      adenylate cyclase (AC) activity by Ho & Sutherland's method. RESULTS: The results
      show that Forskolin significantly lowered the normal IOP of rabbits and blocked
      the ocular hypertension induced by water load in rabbits (P < 0.01). The maximum
      decrease value of 2%, 1% and 0.5% of the Forskolin was 0.59, 0.36 and 0.19 kPa
      (1kPa = 7.5 mmHg), which showed the noticeable dose-effect relationship. Topical
      ocular application of Forskolin lowered IOP in half an hour, reached to a peak in
      2-3 hours and remained significantly for 10 hours. The pupillary diameter did not
      change when IOP was reduced. The Forskolin had potent stimulative properties to
      AC. The greater the ability of the Forskolin to stimulate AC, the stronger the
      effect of IOP lowering. CONCLUSIONS: The Forskolin had the effect on lowering the
      IOP of rabbits. The mechanism of IOP reduction by Forskolin is related to its AC
      activation.

PMID- 8758849
TI  - [Relationship between lead content in umbilical blood and neurobehavioral
      development in infants].
AB  - One hundred and thirty-two babies were selected and their umbilical blood lead
      level were determined as a marker to reflect their exposure, to study the
      diagnostic criteria for lead poisoning in young children. And, mental development
      index (MDI) and psychomotor development index (PDI) of three-month babies in
      Bayley scales of infant development were used as effective indicators to study
      levels of lead on their development. Results indicated that both MDI and PDI in
      infants with blood lead levels of greater than or equal to 0.48 mumol/L were
      obviously lower than those with less than 0.48 mumol/L. All children were divided
      into two groups (high-blood-lead and low-blood-lead) according to the cut-off
      values for blood lead of 0.72, 0.48, and 0.24 mumol/L, respectively, and the
      difference in MDI and PDI between the two groups decreased gradually with the cut
      off value shifted down, and there was no difference in them between the two
      groups when the cut-off point lowering down to 0.24 mumol/L. Therefore, the
      authors recommended that a level of 0.48 mumol/L of blood lead be used as
      diagnostic criteria for lead poisoning in young children.

PMID- 8758850
TI  - [Effects of different modes for health education on mothers' knowledge of baby
      feeding].
AB  - To study the effects of existing different modes of health education on mothers'
      knowledge in feeding babies and young children, 414 mothers with their babies
      aged 0 to 18 months were interviewed with an ad hoc questionnaire in urban and
      rural areas in Guangdong Province during February to April, 1995. Results
      revealed that the best source of mothers' nutritional knowledge was derived from
      a comprehensive mode of health education, the others from mass media and medical
      care professionals, and the last one from mothers' relatives and friends.
      Prenatal training course for baby feeding was one of the effective measures in
      nutritional education, but its effects depended on mothers' occupation and
      cultural level. Baby-friend hospitals played an important role in improvement of
      mothers' knowledge level in breast-feeding. It suggests comprehensive education
      channel, training course for pregnant women, baby-friend hospitals, and so on,
      all are major means of nutritional education for baby feeding.

PMID- 8758851
TI  - [Incidence of insulin dependent diabetes mellitus in children of Shanghai,
      China].
AB  - A retrospective study on incidence of insulin dependent diabetes mellitus (IDDM)
      in children aged 1-14 was conducted in urban districts of Shanghai in 1989-1993.
      There were 1,401,664 children aged 0-14 in the urban area of Shanghai in 1990. 58
      cases of IDDM, 28 boys and 30 girls, were traced from hospitals, primary and high
      schools, kindergartens and nurseries in the city during 1989 to 1993 with a
      "capture-recapture" method in line with DIAMOND protocol sponsored by WHO with
      independent validation of complete case ascertainment, with an average crude
      incidence of 0.83/100,000 (95% CI of 0.61/100,000-10.4/100,000), and a corrected
      incidence of 0.96/100,000 (95% CI of 0.71/100,000-1.18/100,000). Peak incidence
      of IDDM was in 1992 and at age of nine. Age of onset in boys (a median of 8.0
      years) was earlier than that in girls (9.7 years). Incidence of IDDM was
      increasing in Shanghai as compared with the studies in 1980-1991, but it still is
      placed in the lowest throughout the world.

PMID- 8758852
TI  - [Harmfulness of obesity in children to their health].
AB  - With the increase of obese children, harmfulness of obesity to their health was
      studied to lay a basis for formulating corresponding intervention measures. Blood
      sugar, intelligent quotient (IQ), thyroid function, cardiac and pulmonary
      function, and index of gonad development were determined in 150 obese children
      and 150 normal healthy children. Results showed baseline secretion of insulin and
      C-polypeptide in obese children were significantly higher than that in controls,
      and thyroid function, total IQ, speech IQ and operation IQ all were relatively
      lower, cardiac and pulmonary function was significantly lower, and gonad
      development and maturity took place earlier in the former than in those in the
      latter. It indicated that there were a lot of risk factors harmful to their
      health in obese children.

PMID- 8758853
TI  - [Studies on multiple factor intervention in stroke of ten areas in northeast,
      north China and Shanghai].
AB  - In order to explore the ways to prevent from the disease, 4,793 subjects aged
      over 40 at high risk of stroke from a total population of 250,000 in communities
      with high incidence of it were studied with multiple factor intervention, by oral
      administration of "Nao An" capsules as a major measure in 10 areas of north and
      northeast China, as well as Shanghai, during 1990 to 1993. Three years after
      intervention, incidence of stroke decreased by 49.17% in the population, with
      reduction of systolic and diastolic blood pressure, levels of blood sugar,
      cholesterol and triglyceride. Lowering of stroke incidence correlated positively
      with that of blood pressure in the population. It suggests stroke can be
      prevented effectively by concentrated efforts in comprehensive intervention in
      individuals at high risk.

PMID- 8758854
TI  - [Toxicity of cadmium and its mechanism on renal tubular epithelial cells in
      vitro].
AB  - The direct effects of cadmium on the functions and metabolism of renal tubular
      epithelial cells were observed with radio-immune assay, cytochemical and
      biochemical methods to study further the mechanism of nephrotoxicity of cadmium.
      Results revealed uptake of alpha-methyl-D-glucoside (alpha-MG) in renal tubular
      epithelial cells obviously reduced, outflow of potassium ions increased, c-AMP
      content reduced and activity of Na+-K+-ATPase was inhibited significantly after
      exposure to cadmium. Electrochemical gradient of tubular cells maintained by Na+
      K+-ATPase played an important role in transference of sodium and glucose, and
      damage in energy resource system within tubular epithelial cells may be one of
      the pathogenic mechanisms of kidney injury caused by cadmium. In addition,
      changes in a group of biological markers and functional enzymes (alkaline
      phosphatase, AKP; gamma-glutamyltransferase, gamma-GT; lactate dehydrogenase,
      LDH; glucose-6-phosphate dehydrogenase, G-6-PD; N-acetylglucoside, NAG) were
      determined in the study, and it was found that they all could reflect better the
      degree of injury in tubular epithelial cells and their metabolic status and could
      be used in clinical practice.

PMID- 8758855
TI  - [Effects of selenium and germanium on lipid peroxidation in rats fed with low
      selenium grain].
AB  - Rats were fed with grain produced in the area prevalent of Keshan disease for 12
      weeks, by adding certain amount of sodium selenite (Na2SeO3) and
      carboxylethylgermanium (Ge-132) to study the combined effects of selenium and
      germanium on lipid peroxidation and metabolism of free radicals in their bodies.
      Results showed selenium and germanium added to the grain could reduce the content
      of free radicals in rats' liver and kidney tissues, and that of lipid peroxide in
      their heart, liver and kidney, and increase the activities of glutathione
      peroxidase (GSH-Px) in their blood, in a synergic way.

PMID- 8758856
TI  - [Metabolism and utilization of calcium derived from hydrolysed oyster shell in
      rats].
AB  - Experimental rats modeled on calcium deficiency were fed with calcium derived
      from hydrolysed oyster shell, calcium carbonate and calcium chloride
      respectively, equivalent to 45 mg a day, for four weeks to study their
      bioavailability. Calcium contents in the blood, urine, feces and bone of rats
      were determined with atomic absorption spectrometry and EDTA complex titration,
      and their bone density was measured with densitometry. Results showed proportions
      of calcium absorption and retention were 67.3% +/- 16.7% and 64.6% +/- 17.5%,
      respectively, in rats fed with calcium from hydrolysed oyster, and their femur
      calcium content and bone density (BMC/BW) 131.2 +/- 1.48 mg/g and 0.318 +/- 0.034
      g/cm2, respectively, significantly higher than those in the rats fed with calcium
      carbonate. There were no significant difference in blood calcium contents, weight
      gains and feed intake between those three groups of rats. It suggests that
      calcium derived from hydrolysed oyster shell may be absorbed and utilized more
      easily than calcium carbonate.

PMID- 8758857
TI  - [A study on AIDS-related knowledge, attitude and behavior in servicemen in
      China].
AB  - AIDS-related knowledge, attitude and behavior were studied in 1,058 servicemen in
      China with self-administered and anonymous questionnaires. Results showed 76.7%
      to 89.5% of the servicemen surveyed knew correctly the risk of AIDS and its route
      of transmission, but only 8.5% of them answered all the questions listed in the
      questionnaire correctly. Source of their knowledge about AIDS was mainly from
      newspapers, magazines and extracurricular books. Most of them thought they could
      have very little, or no chance to contract the illness. There were 74.0% of the
      servicemen eager to get knowledge about AIDS and 83.2% would like to accept
      relevant testing. And, 80.2% of them answered that they could put their behavior
      under control, or change their unhealthy one to prevent from the illness. It
      indicated that comprehensive and correct publicity and education could play an
      active role in the prevention of HIV infection.

PMID- 8758858
TI  - [Influenced factors of nuclease P1-enhanced 32 P-postlabeling method].

PMID- 8758859
TI  - [Quality of drinking water and its preventive measurements in China].

PMID- 8758860
TI  - [Studies on microcystin contents in different drinking water in highly endemic
      area of liver cancer].
AB  - In order to study the pollution with microcystin (MC), a potent liver promoter,
      in drinking water in highly endemic area of liver cancer, cyanobacteria and its
      product MC were detected in drinking water in Haimen, Jiangsu Province during
      1992 to 1993. Oscillatoria was identified as the most common species of
      cyanobacteria in pond-ditch and river water in Haimen, Jiangsu Province, which
      can produce MC. MC was detected in two of 65 water samples with high performance
      liquid chromatography, liquid chromatography and mass spectrography. In addition,
      studies were conducted in 989 samples collected from drinking water in Haimen,
      Jiangsu Province and more sensitive ELISA was used to detect their MC contents.
      Results showed proportions of samples with positive MC (greater than 50 pg/ml)
      were 17.3%, 31.9%, 4.3% and 0 for pond-ditch, river, shallow and deep well water,
      respectively, with average contents of 101, 160, 68 and 0 pg/ml, respectively.
      Proportions of positive MC samples and average MC contents for pond-ditch water
      were significantly greater than those in shallow and deep well water. It suggests
      studies on relationship between MC and liver cancer should be conducted further.

PMID- 8758862
TI  - [Relationship between aflatoxin and sclerotia production in aspergillus flavus].
AB  - Eighty strains of Aspergillus flavus (AF) isolated from grain produced in
      Zhejiang Province were studied experimentally on their abilities of sclerotia
      production, and 51.3% of the strains could produce sclerotia in Czapek solution
      agar containing 3% sodium nitrate at 30 C incubation for 12 days, with an average
      diameter of 827 +/- 131 microns, and no toxigenic S strain producing abundant
      small sclerotia was found. Most of the toxigenic strains producing sclerotia were
      L strain. There were no significant difference in the rates and amount of
      sclerotia production between toxigenic and a toxigenic strains. There was
      difference in diameter of sclerotia produced between them, with a smaller one in
      the toxigenic strains.

PMID- 8758861
TI  - [A pilot study on trihalomethane formation in water treated by chlorine dioxide].
AB  - Trihalomethane (THM) formation was determined by gas chromatography in water
      disinfected with chlorine dioxide (ClO2) only or ClO2 combined with chlorine
      (Cl2), to lay a basis for water disinfected with ClO2. Results showed no THM was
      produced in water disinfected with ClO2 only if without existence of bromine (Br)
      ion in it; certain amount of bromoform could be formed with existence of bromine
      ion, and THM formation could be inhibited by ClO2 and Cl2, with a ratio of
      greater than 1 between them. Light irradiation could decrease the amount of THM
      produced whether in disinfection with ClO2 or combination with ClO2 and Cl2. No
      significant effect of pH value of water on THM formation was observed, but pH
      should be controlled under neutral or slightly acidic to ensure the concentration
      of ClO2 in water.

PMID- 8758863
TI  - [A study on risk factors of neural tube defects].
AB  - One hundred and twenty-three cases with neural tube defects collected during 1991
      to 1993 from 12 hospitals with birth defect surveillance in Hebei Province, and
      their pair-matched controls were analyzed with single and multiple conditional
      logistic regression to study the effects of food and drinking water on occurrence
      of neural tube defects. Results showed factors contributing to neural tube
      defects were maternal previous history of birth defects, much consumption of
      dried and pickled vegetables during pregnancy, too much nitrate content in
      drinking water (containing more than 10 mg nitrogen per liter of water), less
      consumption of meat, eggs, and beans in their diet.

PMID- 8758864
TI  - [Effects of stress on indices for assessing zinc nutrition status].
AB  - To evaluate the specificity of some functional indices in assessment of body zinc
      nutrition status, we used experimental rat model to observe the effects of some
      factors, such as forced swimming, starvation, trauma and alcohol intoxication on
      zinc the status. Plasma zinc levels of rats significantly decreased after trauma
      increased after starvation. Liver zinc content showed a rising tendency in trauma
      and starvation rats. Activities of superoxide dismutase in red blood cells and
      alkaline phosphatase, mannosidase, 5'-nucleotidase in plasma of rats with alcohol
      intoxication declined significantly. Starvation led to decreased activities of
      alkaline phosphatase and angiotensin-converting enzyme, but increased activities
      of mannosidase. Trauma and forced swimming could cause increase of angiotensin
      converting enzyme activity and decrease of 5'-nucleotidase activity,
      respectively. These results indicate that physiological and pathological effects
      should be excluded from of the above indices as plasma zinc index, in the
      assessment of body zinc nutrition status.

PMID- 8758865
TI  - [Comprehensive cost-benefit evaluation for the improvement of rural water supply
      in Hunan province].
AB  - Comprehensive cost-benefit evaluation for the improvement of rural water supply
      was conducted according to the national standard methods for analysis of water
      quality. Results showed total bacteria count and coliform group count in the
      water declined by 51% after the improvement, and synthetic index of water quality
      declined to 19% of that before the Improvement. Environmental epidemiological
      studies showed yearly incidence of hepatitis A, typhoid fever, diarrhea and
      enteritis decreased by 2.20/1,000, 0.39/1,000, 2.70/1,000 and 14.30/1,000,
      respectively, as compared with those before the improvement, and with the
      manpower capital method, economic loss caused by the above-mentioned diseases
      lowered by 37,238 yuan, economic benefit gained by saving labor-time for water
      taking reached 198,644 yuan, and family income increased 164,188 yuan per year.
      It suggests the above indicators all can be used in comprehensive cost-benefit
      evaluation of the improvement of rural water supply.

PMID- 8758866
TI  - [Protective effects of sodium selenite and selenomethionine on genotoxicity to
      human peripheral lymphocytes induced by arsenic].
AB  - Inhibition bioassay of sister chromatid exchanges (SCE) and DNA synthesis was
      carried out to study the mechanism that selenium, as a chemical agent for
      intervention, could antagonize the effects of arsenic on body damage and lower
      incidence of tumor. Results demonstrated that SCE frequency in peripheral
      lymphocytes induced by As2O3 could be significantly reduced by preincubation with
      5 x 10(-7), 1 x 10(-6) mol/L Na2SeO3 and co-exposure of 1 x 10(-6) mol/L
      selenomethionine. Inhibition of DNA synthesis could be antagonized by
      preincubation in with 5 x 10(-6) mol/L Na2SeO3 and co-exposure of 1 x 10(-6), 5 x
      10(-6) mol/L selenomethionine. But, the mechanism that protective effects of
      selenium on the damage to cell genetic material induced by arsenic should be
      studied further.

PMID- 8758867
TI  - [A study on model of inheritance of systemic lupus erythematosus in Chinese].
AB  - Analysis of segregation and heritability were performed, with the aid of
      Penrose's method, maximum likelihood estimation and Falconer's method, in 215
      cases with systemic lupus erythematosus (SLE) and their pedigrees to explore its
      possible model of inheritance. Results showed that prevalence of SLE in first
      degree relatives of the proband with SLE was 0.85% and higher than that in
      general population (0.03%). A ratio of s/q approached 1/square root q with
      Penrose's method, segregation proportion was equal to 0.029 with simple
      segregation analysis, with a chi-square for goodness-of-fit of 0.0001 (P > 0.05),
      and the heritability of SLE was 56.7% (P < 0.05). It suggests that SLE follows a
      pattern of multifactorial inheritance rather than single-gene one.

PMID- 8758868
TI  - [Screening of high-risk population susceptible to stroke and their
      characteristics].
AB  - High-risk population susceptible to stroke were screened with self-designed
      scoring method for quantitatively evaluating the risk of stroke in 550,000 frame
      population in 22 areas with different incidence of stroke during 1990-1993 and
      its related factors were analyzed by a principal component analysis method.
      Results showed scoring value correlated positively with probabilities of stroke,
      which suggested its objectivity and feasibility. The first principal component
      correlated positively with age, blood pressure, blood sugar, blood cholesterol,
      body mass index, ect., which reflected the characteristics of high risk
      population susceptible to stroke, and 71.43% of those with stroke were in the
      first principal component class. The proportion of the population with the first
      principal component correlated positively with the incidence of stroke in the
      area, therefore, stroke prevention should be focused on such population.

PMID- 8758869
TI  - [Canonical correlation of body composition and pulmonary function in children
      aged eight to twelve].
AB  - Canonical correlation of body composition and pulmonary ventilation function in
      school boys and girls aged 8 to 12 and normally developed was analyzed. Skinfolds
      of triceps and subscapular angle were measured, and body composition was
      estimated as body fat percentage (BF%), body fat (BF) and lean body mass (LBM).
      Ventilation function was measured. Results indicated that correlation between
      body composition and ventilation function mainly attributed to a positive
      correlation between LBM and vital capacity (VC) and a negative correlation
      between BF% and a ratio of expiratory reserve volume (ERV) to VC. It suggests
      effects of body composition on ventilation function mainly attributed to LBM and
      BF%.

PMID- 8758870
TI  - Keeping pace with the evolving management of nonpalpable breast lesions.

PMID- 8758871
TI  - Analysis of malignancy detected by needle-localized breast biopsy.
AB  - The medical records of 192 women with nonpalpable mammographically detected
      breast lesions who underwent needle-localized breast biopsy between January 1989
      and January 1991 and between March 1992 and March 1994 were reviewed. Of the 192
      patients examined, 100 underwent biopsy for evaluation of microcalcifications
      suggestive of malignancy. Ninety-two biopsies were performed for non-specific
      radiodensities not inclusive of microcalcifications. This study examines the
      radiographic characteristics of the nonpalpable breast lesion. Although presence
      of microcalcifications on mammograms are an important finding in detection of
      breast carcinoma, it must not be considered pathognomonic. Other distinguishing
      factors require evaluation to assess the indication for biopsy. Central to this
      study was the presence of microcalcifications alone or as detected in association
      with a dominant mass. Cancer was discriminated in 38 (20%) of the patients
      studied. Mammographic findings with microcalcification, regardless of the
      presence of a mass, were found to be malignant in 20% of patients undergoing
      biopsy. Nine percent of biopsies done to evaluate microcalcifications alone were
      malignant. The finding of microcalcification associated with a dominant mass
      proved malignant in 34% of patients who had a biopsy done. The authors include
      guidelines for increasing the effectiveness of needle-localized biopsies of the
      breast.

PMID- 8758872
TI  - Eustrongylidiasis--a parasitic infection acquired by eating live minnows.
AB  - The objective of this study was to heighten physician awareness of
      eustrongylidiasis by investigating the epidemiology of this parasitic infection.
      The nematode Eustrongylides ignotus was recovered surgically from our patient, in
      whom eustrongylidiasis simulated acute appendicitis. The patient had consumed two
      live minnows obtained from Big Timber Creek of Belmawr, NJ. The authors
      determined the E ignotus infestation rate of free-living minnows at this creek.
      With this data, they approximate the probability of human infection with E
      ignotus after eating live minnows and attempt to evaluate the hypothesis that
      eating live minnows may lead to eustrongylidiasis.

PMID- 8758873
TI  - Osteopathic manipulative treatment applications for the emergency department
      patient.
AB  - The emergency department (ED) setting offers osteopathic physicians multiple
      opportunities to provide osteopathic manipulative treatment (OMT) as either the
      primary therapy or as an adjunct to the intervention. In doing so, osteopathic
      physicians can decrease or eliminate the morbidity and symptoms associated with
      protracted dysfunction. Low back pain, chest pain, torticollis, asthma, and
      sinusitis are some of the illnesses in which OMT should be implemented as part of
      the management plan, note the authors. They provide a guide to the general usage
      of OMT when the aforementioned illnesses present themselves in ED patients, but
      also emphasize the importance of first ruling out any underlying illnesses that
      could be manifested by musculoskeletal symptoms.

PMID- 8758874
TI  - The power of words: communicating effectively with young patients.
AB  - Communication skills are the cornerstone of the doctor-patient relationship. This
      article provides clinically helpful hints to practitioners working with children
      and families. Specific examples of clinical phrases are presented along with
      alternative phrases that may enhance the clinical process.

PMID- 8758875
TI  - Metaplastic breast carcinoma.
AB  - Metaplastic breast carcinoma, a rare entity, accounts for only about 0.02% of all
      breast carcinomas. It involves the transformation of mammary neoplasms into
      osteoid and chondroid substances. Because of the relatively small patient
      population and the limited number of controlled studies, there is confusion
      regarding its classification and staging. Its histogenesis is unknown. The
      authors describe a 65-year-old woman with findings consistent with metaplastic
      breast carcinoma. Theories as to etiology and prognosis as well as treatment are
      discussed.

PMID- 8758876
TI  - Use of computed tomography guidance and mammographic hook wires to remove
      displaced, embedded contraceptive rods.
AB  - Because of dysfunctional uterine bleeding, a patient requested removal of
      levonorgestrel contraceptive rods. The patient was referred to a general surgeon
      by her gynecologist who was unable to palpate the rods in the region of
      implantation in her left upper arm. Initially, the surgeon was able to locate and
      remove four of the six previously implanted rods. Because these implants are not
      visible under convention radiography or fluoroscopy, computed tomography was used
      to locate the remaining two rods. After localization by use of mammographic hook
      wires, the remaining two rods were successfully removed surgically.

PMID- 8758877
TI  - Effects of thyroid hormone treatment on 31P-NMR spectroscopy of muscle and on
      nerve conduction studies in a patient with long-standing severe hypothyroidism.
AB  - Hypothyroidism exerts a significant effect on several body systems, including the
      functioning of muscle and nerve. Described here is the case of a severely
      hypothyroid patient with weakness and numbness of the legs who showed marked
      clinical improvement with thyroid hormone treatment. Concurrently obtained
      phosphorus 31-nuclear magnetic resonance (NRM) spectra and nerve conduction
      studies showed changes in muscle phosphorus metabolism with increases in
      conduction velocities. Phosphorus 31-NMR spectroscopy is useful for evaluating
      metabolism in muscle in hypothyroid patients.

PMID- 8758878
TI  - Churg-Strauss syndrome.
AB  - The neurologic manifestations of systemic necrotizing vasculitis are
      heterogeneous and often complex. Late onset asthma, systemic vasculitis manifest
      by mononeuritis multiplex, and peripheral eosinophilia-the triad of which is
      consistent with Churg-Strauss syndrome-developed in a 59-year-old woman.
      Electromyography and nerve conduction studies showed both myelinating and axonal
      neuropathy involving multiple nerves. Muscle and nerve biopsy showed neurogenic
      atrophy, demyelination, and axonal changes involving the sural nerve and
      inflammatory necrotizing small and medium vessel arterial changes. The patient
      was treated with high-dose prednisone and improved rapidly. Unusual in this case
      was the lack of multisystemic involvement. Churg-Strauss syndrome is a disease
      that is being recognized with increased clinical frequency and responds quickly
      to methylprednisolone treatment.

PMID- 8758879
TI  - Acute appendicitis secondary to non-0 group I Vibrio cholerae.
AB  - Acute appendicitis is the most common abdominal surgical condition and is usually
      associated with colonic flora. The patient described had acute appendicitis
      associated with an uncommon microorganism. This report underscores the importance
      of obtaining an adequate occupational, travel, and dietary history.

PMID- 8758880
TI  - Application of a self-modeling curve resolution approach to the study of solvent
      effects on the acid-base and copper (II)-complexing behavior of polyuridylic
      acid.
AB  - The solvent effect on the acid-base and complexation behavior of the
      homopolynucleotide polyuridylic acid (poly(U)) has been studied by means of
      potentiometric and spectrometric titrations (circular dichroism and UV-VIS) in
      water and in 30 and 50% (v/v) dioxane-water media. The potentiometric studies
      revealed the absence of polyelectrolytic effects in the acid-base equilibrium,
      and the spectrometric experiments detected only a random coil conformation
      associated with both the protonated and deprotonated species. The common behavior
      observed in the three media seems to indicate the weakness of both intramolecular
      interactions, i.e., base stacking, and solute/solvent interactions, i.e.,
      hydrogen-bonding, and consequently their small effect during the protonation
      process. Differences regarding the solubility of the deprotonated species in the
      solvents used are due to the difficult stabilization of such a charged species in
      the low polar environment of the dioxane-water mixtures. Complexation has been
      exhaustively studied in aqueous media, and no conformational changes have been
      noticed in the only copper(II)-poly(U) complex detected. The inclusion of the
      copper(II) ion in the macromolecular skeleton of the polynucleotide does not
      contribute to an ordination of the structure, which remains as a random coil. No
      comparison between this equilibrium in aqueous solution and in the hydroorganic
      mixtures could be carried out since the limited pH range of the soluble complex
      in those solvent mixtures prevented a rigorous quantitative monitoring of such a
      chemical process.

PMID- 8758881
TI  - A new method for the voltammetric response of hemoglobin.
AB  - Hemoglobin (Hb) could give a voltammetric response after it was acted on by the
      surfactant dodecyl benzene sodium sulfonate (DBS) or sodium dodecyl sulfate
      (SDS). The mechanism might be the enhancement of the adsorption process when
      there was surfactant in the protein solution. Moreover, the macromolecules might
      open their electroactive sections after they interacted with the hydrophobic
      groups of the surfactant. Comparative studies showed that DBS could make Hb
      present a more welcome result than SDS since it had an extra benzene ring. On the
      other hand, since surfactant was a denaturant to Hb as well and the electrode
      surface might be fouled with it, a negative effect of the surfactant should be
      considered in the meantime.

PMID- 8758882
TI  - Magnetic properties of tunicate blood cells. II. Ascidia ceratodes.
AB  - The magnetic properties of intact blood cells of the tunicate Ascidia ceratodes
      have been measured up to 50 kOe with a SQUID susceptometer. Analysis of total
      metal contents by plasma emission spectroscopy and V(IV) content by epr indicates
      that approximately 5% of the accumulated vanadium is +4 vanadyl ion. Measured
      values of the magnetic moment Mp at different values of the applied magnetic
      field H over the temperature range T = 2-100 K depend on the magnitude of the
      field indicating magnetic anisotropy of the ground state. The slope of the Mp vs.
      H/T curve at high temperature is significantly higher than expected from electron
      spin S = 1 per vanadium(III) ion. The model that fits these data best is a dimer
      with one V(III) S = 1 ion ferromagnetically coupled to a second V(III) S = 1 ion,
      with spin-coupling constant J = 3.5 cm-1, and 5% of the total vanadium content in
      the form of a V(IV) S = 1/2 ion. Since vanadium in A. ceratodes is known to
      reside in at least three different types of blood cell, the excellent fit
      indicates that the metal is stored predominantly as a dimer regardless of blood
      cell type. Ferromagnetic coupling implies that the two vanadium ions in the dimer
      are connected by an unprotonated mu-oxo bridge.

PMID- 8758883
TI  - The Drug Involvement Scale for Adolescents (DISA).
AB  - This article specifically addressed the need for a multidimensional approach to
      measuring adolescents' drug involvement. The Drug Involvement Scale for
      Adolescents (DISA) was theoretically specified and its measurement properties
      were tested using Confirmatory Factor Analyses and traditional procedures with
      705 high-risk and typical high school students. Five first-order dimensions, Drug
      Access, Alcohol Use, Other Drug Use, Drug Use Control Problems and Adverse Drug
      Use Consequences, and a hierarchical model of Drug Involvement demonstrated a
      good fit between model and data. Further, the DISA demonstrated good internal
      consistency (alpha = .91); correlated as expected with known correlates of
      adolescent drug use; discriminated drug involvement between high-risk and typical
      high school students; and predicted later drug involvement and known drug-related
      consequences among adolescents. The results suggest the DISA should be useful for
      capturing a multidimensional view of adolescent drug involvement in both
      etiologic and prevention studies. A major advantage of the DISA is its brevity:
      twenty-two indicators constructed from twenty-nine items.

PMID- 8758884
TI  - Early prevention of alcohol and other drug use among adolescents.
AB  - Among a variety of methods to prevent drug use among adolescents, school
      community based prevention and intervention programs are prevalent. The impact of
      such programs will be compromised, however, if drug use among adolescents is
      impacted by forces apart from the impact of school-community prevention and
      intervention, such as the function of the family. On the other hand, prevention
      and intervention programs can have a powerful impact if teenage drug use is
      responded to through early intervention. The purpose of this study was to review
      a sample of students referred for drug assessments to determine how early
      intervention should occur and how involved high school and middle school students
      are with alcohol and other drugs.

PMID- 8758885
TI  - Adolescent counterarguing of TV beer advertisements: evidence for effectiveness
      of alcohol education and critical viewing discussions.
AB  - The pervasiveness of American youth's exposure to alcohol advertising is well
      documented, as is the correlational evidence linking such exposure to alcohol
      related attitudes, use, and expectancies. While efforts to train young people to
      resist persuasive appeals are often made in alcohol education programs, little
      evidence exists concerning the effectiveness of such efforts. The present study
      (N = 83) found that recency of exposure to alcohol education classes and
      discussion of alcohol advertising in such classes predicts cognitive resistance
      (counterarguing) of such advertisements months or even years after class
      exposure. Age, gender, and ethnicity were statistically controlled. While females
      tended to counterargue the alcohol advertisements more than did males, there was
      no statistically significant difference in the impact of education on males and
      females.

PMID- 8758886
TI  - Drug education and the college athlete: evaluation of a decision-making model.
AB  - In general there is a lack of information describing the components and structure
      of drug education and prevention programs (DEPP) for college student athletes.
      While concern about the prevalence of drug abuse among college student athletes
      has increased, a relative lack of clarity remains regarding what elements of drug
      education prevention programs have been successful or unsuccessful in this
      setting. In an effort to address this issue at Oregon State University a two
      credit ten-week DEPP was implemented as a requirement for all collegiate
      athletes. This article describes the evaluation of this program. Altogether 635
      student athletes from three National Collegiate Athletic Association (NCAA)
      Division One universities provided data in this two-year evaluation project.
      Participants were student athletes from Oregon State University (OSU), a Mid
      Western University (MWU), and another Pacific North-Western University (PNWU).
      Pre- and post-test data were collected regarding knowledge about drugs, attitudes
      toward drug use, drug use, and decision-making factors. Students at OSU and MWU
      were enrolled in a structured DEPP, and the third group from PNWU was used as a
      control and did not receive regular instruction. The baseline data taken before
      the drug education course indicated that athletes at OSU, MWU, and PNWU were no
      different in their knowledge of drugs, attitudes toward drugs, or perception of
      the value of drug education in preventing drug abuse among student athletes.
      However, the data at the end of the ten-week course revealed many significant
      improvements among OSU and MWU students athletes, in knowledge, attitude related
      to performance enhancing drugs and recreational drugs, and perceptions of drug
      education. At the end of the course 88 percent of the participating OSU athletes
      agreed that drug education can be effective in preventing drug abuse among
      student athletes.

PMID- 8758887
TI  - Loss-grief addiction model.
AB  - This group study features a loss-grief inventory in the treatment of ninety-eight
      substance abusers in a public outpatient treatment facility. The inventory serves
      as both assessment and treatment tools. That is, the inventory helps the
      counselor and the client to identify unresolved loss-grief issues which may
      contribute to the addiction; it also serves as a treatment tool to assist the
      client through the grieving process. In identifying losses, the client has three
      time categories from which to choose: 1) pre-addiction losses; 2) losses
      associated with the addiction; and 3) losses associated with entering treatment.
      An additional feature of the inventory illustrates a simplified procedure to
      compute the client's unresolved loss-grief level through use of a 5-point Likert
      scale.

PMID- 8758888
TI  - A survey of training needs of experienced certified addictions counselors.
AB  - The alcohol and other drug abuse field has, more often than not, determined the
      topics of education and training be directed by published authors and associated
      authority figures. Rarely do workshop instructors ask the field what they would
      like to see presented, or how they prefer the information to be conveyed. A
      recent survey was conducted by The Pennsylvania State University and the
      Pennsylvania Chemical Abuse Certification Board to address these questions. The
      results indicate a preference for training topics that encompass cultural issues,
      alternative forms of treatment and relapse prevention. The preferred style of
      delivery was that via discussion groups and lectures. Data such as this needs to
      be weighed into future drug and alcohol education.

PMID- 8758889
TI  - How selective is the transporter associated with antigen processing?

PMID- 8758890
TI  - CD95-induced apoptosis of lymphocytes in an immune privileged site induces
      immunological tolerance.
AB  - We examined the relationship between cell death and tolerance induction following
      antigen injection into the anterior chamber of the eye. Our data show that when
      inflammatory cells undergo apoptosis following infection with HSV-1, tolerance to
      the virus was observed. In contrast, when cell death was absent due to defects in
      Fas or FasL, immune tolerance was not observed. Further studies revealed that
      cell death and tolerance required that the lymphoid cells be Fas+ and the eye be
      FasL+. Additionally, we show that while Fas/FasL-mediated apoptosis occurred in
      the eye, it was apoptotic cell death that was critical for tolerance induction.
      Our results further demonstrate immune privilege is not a passive process
      involving physical barriers, but is an active process that employs an important
      natural mechanism to induce cell death and immune tolerance.

PMID- 8758891
TI  - The roles of Fas/APO-1 (CD95) and TNF in antigen-induced programmed cell death in
      T cell receptor transgenic mice.
AB  - The possible involvement of Fas/APO-1 (CD95) and TNF in antigen-specific AICD of
      thymocytes and mature T cells has been investigated. Antigenic stimulation in
      vivo of influenza hemagglutinin (HA)-specific TCRtg mice was used to demonstrate
      that the kinetics of thymocyte and peripheral CD4+ T cell deletion are similar in
      mice with normal (+/+) or defective Fas (lpr/lpr) background, indicating that a
      Fas-independent pathway(s) is responsible for the deletion of activated T cells.
      TCRtg-+/+ or TCRtg-lpr/lpr mice injected with murine TNF-blocking MAb (TN3)
      showed rapid apoptosis of thymocytes after HA stimulation, indicating that death
      signaling through Fas and TNF receptors is not essential for HA-induced thymocyte
      deletion. CDC peripheral T cells in TCRtg-lpr/lpr mice did not undergo apoptosis
      following injection with HA and TN3, indicating that TNF-mediated apoptosis is
      involved in the deletion of mature T cells after antigenic stimulation. However,
      apoptosis still occurred in TCRtg-+/+ mice injected with TN3, indicating that
      both Fas- and TNF-mediated cell death can contribute to the deletion of activated
      peripheral T cells.

PMID- 8758892
TI  - TGF beta 1 inhibits NF-kappa B/Rel activity inducing apoptosis of B cells:
      transcriptional activation of I kappa B alpha.
AB  - TGF beta 1 treatment of B cell lymphomas decreases c-myc gene expression and
      induces apoptosis. Since we have demonstrated NF-kappa/Rel factors play a key
      role in transcriptional control of c-myc, we explored the effects of TGF beta1 on
      WEHI 231 immature B cells. A reduction in NF-kappa B/Rel activity followed TGF
      beta 1 treatment. In WEHI 231 and CH33 cells, we observed an increase in I kappa
      B alpha, a specific NF-kappa B/Rel inhibitor, due to transcriptional induction.
      Engagement of surface CD40 or ectopic c-Rel led to maintenance of NF-kappa B/Rel
      and c-Myc expression and protection of WEHI 231 cells from TGF beta 1-mediated
      apoptosis. Ectopic c-Myc expression overrode apoptosis induced by TGF beta 1.
      Thus, downmodulation of NF-kappa B/Rel reduces c-Myc expression, which leads to
      apoptosis in these immature B cell models of clonal deletion. The inhibition of
      NF-kappa B/Rel activity represents a novel TGF beta signaling mechanism.

PMID- 8758893
TI  - Duration of TCR stimulation determines costimulatory requirement of T cells.
AB  - Current models suggest that T cells that receive only signal-1 through antigenic
      stimulation of the T cell receptor (TCR) become anergic, but will mount an immune
      response when a costimulatory signal-2 is provided. Using mice deficient for an
      important costimulatory molecule, CD28, we show that a transient signal-1 alone,
      either through infection with an abortively replicating virus, or through
      injection of viral peptide, anergizes CD8+ T cells, demonstrating the biological
      relevance of T cell anergy in vivo. However, in the absence of CD28, continued
      presence of signal-1 alone, either through prolonged viral replication or
      repeated injection of peptide, prevents the induction of anergy and generates a
      functional T cell response in vivo.

PMID- 8758894
TI  - A TCR binds to antagonist ligands with lower affinities and faster dissociation
      rates than to agonists.
AB  - T lymphocyte activation is mediated by the interaction of specific TCR with
      antigenic peptides bound to MHC molecules. Single amino acid substitutions are
      often capable of changing the effect of a peptide from stimulatory to
      antagonistic. Using surface plasmon resonance, we have analyzed the interaction
      between a complex consisting of variants of the MCC peptide bound to a mouse
      class II MHC (Ek) and a specific TCR. Using both an improved direct binding
      method as well as a novel inhibition assay, we show that the affinities of three
      different antagonist peptide-Ek complexes are approximately 10-50 times lower
      than that of the wildtype MCC-Ek complex for the TCR, largely due to an increased
      off-rate. These results suggest that the biological effects of peptide
      antagonists and partial agonists may be largely based on kinetic parameters.

PMID- 8758895
TI  - Identification of an H2-M3-restricted Listeria epitope: implications for antigen
      presentation by M3.
AB  - Using expression cloning, we have identified an H2-M3-restricted epitope of the
      intracellular bacterial pathogen Listeria monocytogenes. Picomolar concentrations
      of an amino-terminal N-formylated hexapeptide, fMIGWII, targeted cells for lysis
      by CD8+ cytotoxic T cells, while the nonformylated peptide was approximately 100
      fold less active. The sequence of the 185 aa protein source of this epitope
      predicts a transmembrane protein that retains its N terminus and assumes an
      N(out)-C(in) topology. This membrane orientation offers an explanation for the
      protection of the epitope from deformylases present in the bacterial cell and
      suggests an explanation for the ability of phagocytes to present H2-M3-restricted
      bacterial epitopes via a vacuolar TAP-independent mechanism.

PMID- 8758896
TI  - A Listeria monocytogenes pentapeptide is presented to cytolytic T lymphocytes by
      the H2-M3 MHC class Ib molecule.
AB  - Polymorphism of MHC class Ia molecules severely constrains vaccine development
      against intracellular pathogens. Antigen presentation by MHC class Ib molecules,
      which are generally conserved between different individuals, may circumvent this
      obstacle. Herein, we use tandem mass spectrometry to identify a Listeria
      monocytogenes pentapeptide antigen that is presented to T lymphocytes by the H2
      M3 MHC class Ib molecule. The peptide contains N-formyl methionine at the N
      terminus and exclusively hydrophobic amino acids. Mice of the H-2 d, H-2 b,and H
      2 k haplotypes respond to this peptide upon infection with Listeria
      monocytogenes. Identification of antigens presented by MHC class Ib molecules is
      feasible and may provide opportunities for relatively unrestricted vaccine
      development.

PMID- 8758897
TI  - Distinct tumorigenic potential of abl and raf in B cell neoplasia: abl activates
      the IL-6 signaling pathway.
AB  - The development of murine plasma cell tumors induced by raf/myc containing
      retroviruses is facilitated by T cells and completely dependent on IL-6. To
      determine whether kinases with differing specificities reflect alternative
      biochemical pathways in B cell tumorigenesis, we have employed an abl/myc
      containing retrovirus to assess neoplastic development. In contrast with raf/myc,
      abl/myc disease is T cell and IL-6 independent. An examination of the IL-6 signal
      transduction pathway reveals that this pathway, as defined by activation of
      Stat3, is inducible by IL-6 in raf/myc tumors but constitutively activated in
      abl/myc tumors. These findings provide a mechanism for the derivation of cytokine
      independent plasma cell tumors and suggest that both IL-6-dependent and
      independent tumors may arise in vivo depending on the particular mutational
      events incurred during tumorigenesis.

PMID- 8758898
TI  - C/EBP activators are required for HIV-1 replication and proviral induction in
      monocytic cell lines.
AB  - Previous work has shown that C/EBP sites and C/EBP transcriptional activators are
      necessary for HIV-1 LTR activity in monocytes/macrophages. We have investigated
      the role that C/EBP proteins play in induction and replication of HIV-1. Ectopic
      expression of the dominant negative C/EBP protein LIP inhibited HIV-1 mRNA and
      virus production in activated U1 cells, demonstrating that C/EBP proteins are
      required for provirus induction. U1 lines overexpressing C/EBP activator NF-IL-6
      produced more viral mRNA and virus particles following cellular activation than
      control lines, demonstrating that C/EBP proteins are limiting for virus
      transcription. HIV-1 harboring mutations within two C/EBP sites were crippled in
      their ability to replicate in U937 promonocytic cells, indicating that these
      sites are required for replication. These data identify C/EBP proteins as
      regulators of HIV-1 expression in monocytes/macrophages.

PMID- 8758899
TI  - Insulin receptor substrate 1 overexpression in human hepatocellular carcinoma
      cells prevents transforming growth factor beta1-induced apoptosis.
AB  - Insulin-like growth factors initiate tyrosyl phosphorylation of the insulin
      receptor substrate I (IRS-I) protein and activate multiple signaling pathways
      essential for liver growth. This gene has been found to be up-regulated in human
      hepatocellular carcinomas (HCCs), and overexpression of IRS-1 in NIH 3T3 cells
      leads to malignant transformation with activation of the mitogen-activated
      protein kinase cascade. To explore another possible role of IRS-I in
      hepatocarcinogenesis, we examined the capability of transforming growth factor
      beta1 (TGF-beta1), a known negative regulator of hepatocyte growth, to induce
      programmed cell death in the context of IRS-I overexpression. Hep3B HCC cells
      were stably transfected with a retroviral vector containing the IRS-I gene. The
      overexpressed IRS-I protein was highly tyrosyl phosphorylated following
      insulin/insulin- like growth factor I stimulation and led to constitutive
      activation of downstream signal transduction molecules such as
      phosphatidylinositol-3 kinase and mitogen-activated protein kinase. Although
      parental Hep3B cells were sensitive to apoptosis, the Hep3B-IRS-I-transfected
      cells acquired resistance to TGF-beta1-induced programmed cell death. Our
      investigations suggest that IRS-I-mediated signals may act as survival factors
      and protect against TGF-beta1-induced apoptosis in HCC; this phenomenon may
      contribute to hepatic oncogenesis.

PMID- 8758900
TI  - Inhibition of 2-Amino-1-methyl-6-phenylimidazo[4,5]pyridine-induced lymphoma
      formation by oltipraz.
AB  - 2-Amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and
      carcinogenic heterocyclic amine present in pyrolysate products of meat and fish
      and has been shown to induce tumors in the colon, mammary gland, and possibly
      lymphatic system. Experiments were designed to examine the lymphoma-inducing
      capacity of PhIP and to test the inhibitory effects of oltipraz on PhIP-induced
      lymphomas in male F344 rats. Beginning at 5 weeks of age, groups of rats were fed
      the diets containing 0, 200, and 400 ppm oltipraz with or without 100-400 ppm
      PhIP. All animals were continued on this regimen until the 58th week. The results
      indicate that administration of PhIP produced lymphomas in 75% of rats. Most of
      the large lymphomas were thymomas (65%), and these lymphomas developed in less
      than 6 months. Death of animals during the course of the study was due to
      suffocation produced by a large lymphoma that filled the entire thoracic cavity,
      resulting in collapse of the lungs. Administration of 200-400 ppm oltipraz
      significantly protected rats from PhIP-induced toxicity; most of the rats
      survived until termination of the experiments. It is noteworthy that the addition
      of oltipraz at 200 and 400 ppm in the diet suppressed the PhIP-induced lymphomas
      to 90-100%. In conclusion, PhIP-induced lymphomas in the laboratory rat appears
      to be a very useful model to analyze the genesis of lymphomas, and oltipraz
      serves as a potential chemopreventive agent for lymphomas.

PMID- 8758901
TI  - Injection of complementary DNA encoding interleukin-12 inhibits tumor
      establishment at a distant site in a murine renal carcinoma model.
AB  - Interleukin (IL-12) protein has been shown to elicit diverse immunological
      responses and potent antitumor activity. We demonstrate here that intradermal
      injection of IL-12 cDNA induces systemic biological effects characteristic of the
      cytokine in vivo. Intradermal injection of IL-12 cDNA resulted in local
      expression of IL-12 mRNA, which correlated with a 10-fold increase in natural
      killer activity and a 3-4-fold increase in anti-CD3-induced IFN-gamma production
      in cultured splenocytes. Furthermore, when challenged with Renca tumor cells at a
      distant site, the day of tumor emergence was significantly delayed, and tumor
      growth was reduced in mice that received IL-12 cDNA, compared to mice given
      injections of plasmid vector alone. A number of the mice receiving IL-12 cDNA
      injections remained tumor free months after tumor challenge. In contrast to mice
      receiving recombinant IL-12 protein, no splenomegaly was detected when natural
      killer activity was significantly induced in mice receiving injections of IL-12
      cDNA. Because purified plasmid DNA is more economical to prepare and has a longer
      shelf-life than recombinant proteins, and intradermal administration of cDNA
      encoding IL-12 did not cause splenomegaly, our findings suggest that the in vivo
      injection of cDNA encoding IL-12 may be a less toxic and more cost-effective
      alternative to IL-12 protein therapy in some clinical or experimental therapeutic
      applications.

PMID- 8758902
TI  - Antiangiogenic treatment with linomide as chemoprevention for prostate, seminal
      vesicle, and breast carcinogenesis in rodents.
AB  - There are two distinct phases during prostatic carcinogenesis with regard to
      tumor blood vessel development. During the first or prevascular phase, which may
      persist for years, cells that have undergone some but not all of the
      transformation steps undergo a limited amount of net growth, producing
      premalignant prostatic intraepithelial neoplastic (PIN) lesions. Most of these
      PIN lesions do not continue net growth and do not progress to produce
      histologically detectable cancer. Even the PIN lesions that do progress to cancer
      remain of limited virulence unless they undergo conversion to the second or
      angiogenic phase. Once this angiogenic phase is reached, new blood vessel
      development is greatly enhanced within the cancer. It is this enhanced tumor
      angiogenesis which allows these cancers both to grow continuously and to
      metastasize. Thus, inhibition of angiogenesis should be an effective
      chemopreventive approach for prostatic carcinogenesis. Linomide is a low
      molecular weight, water-soluble agent with excellent p.o. absorption and
      bioavailability. We have previously demonstrated that daily p.o. treatment with
      Linomide has antiangiogenic abilities against a series of rat and human prostatic
      cancer xenografts growing in vivo. In the present studies, we have demonstrated
      using Matrigel in in vivo angiogenesis assays that daily p.o. Linomide at 25
      mg/kg/day inhibits angiogenesis induced by tumor necrosis factor alpha, acidic
      fibroblast growth factor, basic fibroblast growth factor, and vascular
      endothelial growth factor. Using an N-methylnitrosourea initiation-androgen
      promotion model, Linomide was given p.o. at a daily dose as high as 25 mg/kg/day
      for at least 1 year without major toxicity while inhibiting the development of
      seminal vesicle/prostate cancers in male rats by >50%. Dose-response analysis
      demonstrated that a Linomide blood level of 50-100 microM is optimal for such
      chemoprevention. In addition, Linomide treatment at a dose of 25 mg/kg/day was
      able to inhibit by approximately 60% the incidence of N-methylnitrosourea and
      approximately 50% of 7,12-dimethyl-benz(a)anthracine-induced mammary
      carcinogenesis in female rats.

PMID- 8758903
TI  - A common mutation in BRCA2 that predisposes to a variety of cancers is found in
      both Jewish Ashkenazi and non-Jewish individuals.
AB  - Recent studies have identified mutations in the breast and (ovarian cancer
      susceptibility gene 2 (BRCA2), one which has been found in the germline of
      several males and one female affected with breast cancer. To establish the
      carrier frequency of this mutation in a large population of individuals affected
      with cancer, we evaluated constitutional DNA isolated from 83 individuals
      diagnosed with breast cancer and 93 diagnosed with ovarian cancer at any age, 42
      of whom reported a family history of cancer. Using a simple allele-specific PCR
      based nonradioactive method, we detected a total of eight individuals (4.5%)
      carrying a 1-bp deletion at nucleotide 6174 of the BRCA2 gene (6174delT). The age
      of disease onset in the mutant allele carriers was highly variable and typically
      late onset (41-72 years for breast cancer and 48-73 years for ovarian cancer).
      Evaluation of family histories for the eight mutant allele carriers revealed that
      several individuals had significant cancer histories that included, in addition
      to breast and/or ovarian cancer, an increased incidence of colon, esophageal,
      pancreatic, stomach, and hematopoietic cancers. Interestingly, seven of the eight
      individuals were of Ashkenazi Jewish descent. Haplotype data for the mutant
      allele carriers using markers spanning the region of the BRCA2 gene on chromosome
      13ql2-ql3 suggest that only two of the confirmed Jewish Ashkenazi individuals
      share a single common ancestry, indicating several independent origins for this
      mutation. These data provide evidence for the presence of a specific BRCA2
      mutation which has its origins in both Jewish Ashkenazi and non-Jewish
      populations. The observed overrepresentation of specific mutations within a
      subgroup of the general population may eventually help contribute to the
      development of inexpensive and routine tests such as the one described in our
      study.

PMID- 8758904
TI  - Rb and p16INK4a expression in resected non-small cell lung tumors.
AB  - Inactivation of the cyclin-dependent kinase inhibitor p16INK4a (CDKN2/MTS1) is
      documented in a wide variety of cancer cell lines and tumors. We have shown that
      loss of p16INK4a protein expression is a common event in early stage non-small
      cell lung cancer (NSCLC), correlates with a significantly worse survival, and is
      more common in higher stage disease. One hundred NSCLC tumors from patients
      undergoing definitive thoracotomies at a single institution were examined for
      p16INK4a and retinoblastoma protein (pRB) expression. Abnormal pRB staining was
      identified in 15% of the tumors, whereas 51% possessed aberrant p16INK4a protein
      expression. Tumors with aberrant expression of p16INK4a by immunohistochemistry
      were associated with a significantly worse survival (P=0.04). Additionally, the
      inverse correlation of pRB and p16INK4a expression previously noted in lung
      cancer cell lines and tumors was confirmed in this large cohort of patients, with
      65% of the tumors demonstrating inverse expression of pRB and p16INK4a
      (p=0.00019). A statistically significant increase in aberrant p16INK4a
      expression, as well as inverse expression of p16INK4a and pRB, was seen with
      increasing pathological stage of disease. These findings establish the prognostic
      significance (of the absence of p16INK4, in resected NSCLC and confirm the
      critical importance of disrupting the pathway of cyclin-dependent kinase-mediated
      phosphorylation of pRB in the molecular oncogenesis and progression of NSCLC.

PMID- 8758905
TI  - Familial predisposition to neuroblastoma does not map to chromosome band 1p36.
AB  - Familial predisposition to neuroblastoma, a common embryonal cancer of childhood,
      segregates as an autosomal dominant trait with high penetrance. It is therefore
      likely that neuroblastoma susceptibility is due to germ line mutations in a tumor
      suppressor gene. Cytogenetic, functional, and molecular studies have implicated
      chromosome band 1p36 as the most likely region to contain a suppressor gene
      involved in sporadic neuroblastoma tumorigenesis. We now demonstrate that
      neuroblastoma predisposition does not map to any of eight polymorphic markers
      spanning 1p36 by linkage analysis in three families. In addition, there is no
      loss of heterozygosity at any of these markers in tumors from affected members of
      these kindreds. Furthermore, there is strong evidence against linkage to two
      Hirschsprung disease (a condition that can cosegregate with neuroblastoma)
      susceptibility genes, RET and EDNRB. We conclude that the neuroblastoma
      susceptibility gene is distinct from the 1p36 tumor suppressor and the currently
      identified Hirschsprung disease susceptibility genes.

PMID- 8758906
TI  - P210 Bcr-Abl interacts with the interleukin 3 receptor beta(c) subunit and
      constitutively induces its tyrosine phosphorylation.
AB  - Chronic myelogenous leukemia is a neoplasm of pluripotent hematopoietic cells.
      The P210 Bcr-Abl oncoprotein is a deregulated cytoplasmic tyrosine kinase that
      has been shown to cause chronic myelogenous leukemia-like neoplasms in mice.
      Cytokines such as interleukin 3 and granulocyte/macrophage-colony-stimulating
      factor regulate the growth and differentiation of hematopoietic precursors. These
      cytokines activate two distinct signals to the nucleus. One signal is through the
      Ras pathway, and the second involves activation of Jak2. We demonstrated that Bcr
      Abl co-immunoprecipitates with, and constitutively phosphorylates, the common
      beta(c) subunit of the interleukin 3 and granulocyte/macrophage-colony
      stimulating factor receptors. Our data show that formation of this complex leads
      to the constitutive tyrosine phosphorylation of Jak2. It has been demonstrated
      that Bcr-Abl interacts with Grb2 and Shc, which in turn activates the Ras
      pathway. Our new findings raise the possibility that Bcr-Abl activates signaling
      through both pathways in a factor-independent fashion.

PMID- 8758907
TI  - Suppression of human bladder cancer growth by increased expression of C-CAM1 gene
      in an orthotopic model.
AB  - Recently, we demonstrated that an immunoglobulin-like cell adhesion molecule, C
      CAM, acts as a tumor suppressor in prostate cancer. It is known that C-CAM is
      expressed in many epithelial cell types. In this study, we tested the possibility
      that C-CAM may also suppress bladder cancer progression. We used an orthotopic
      tumor model, which provides a relevant organ condition for examining the
      interaction between primary tumor cells and their microenvironment; this
      interaction has a critical impact on the behavior of carcinoma. We constructed a
      recombinant adenovirus expressing C-CAM1 (an isoform of C-CAM) and infected the
      253J B-V cell line, a tumorigenic human bladder carcinoma subline. In vitro, C
      CAM1 protein was detected in C-CAM1 adenovirus-infected cells but not in
      antisense control virus-infected cells, and the levels of expression showed dose
      dependency. When these cells were injected orthotopically in nude mice, we found
      that the increased expression of C-CAM1 in the 253J B-V cells repressed the
      growth of 253J B-V-induced tumors. Taken together, these data indicate that C
      CAM1 is a potent tumor suppressor in human bladder cancer.

PMID- 8758908
TI  - Oncogenic transformation and hypoxia synergistically act to modulate vascular
      endothelial growth factor expression.
AB  - Hypoxia can select for cells that have lost their apoptotic potential, thereby
      making them resistant to adverse conditions. However, long-term survival of
      transformed cells which have diminished apoptotic sensitivity when exposed to low
      oxygen conditions would require the activation of their angiogenic program to
      compensate for an insufficient oxygen supply. In this report, we show that the
      activity (of oncogenic Ha-ras, either constitutively or transiently, enhances the
      induction of the angiogenic mitogen, vascular endothelial growth factor (VEGF),
      by hypoxia. Analysis of the 5' flanking region of the VEGF promoter indicates
      that a HIF-1-like sequence is to promote a 15-fold increase in reporter gene
      activity in Ha-ras-transformed cells when exposed to hypoxia, whereas mutations
      in the same site totally inhibited VEGF induction. Under low oxygen conditions,
      VEGF induction is inhibited in cells expressing a mutant inhibitory allele of Ha
      ras (RasN17), indicating a direct role for Ras in modulating VEGF activity. We
      propose that the angiogenic switch in Ras-transformed cells may be
      physiologically promoted by the tumor microenvironment through VEGF induction.

PMID- 8758909
TI  - Independent amplification and frequent co-amplification of three nonsyntenic
      regions on the long arm of chromosome 20 in human breast cancer.
AB  - DNA amplification at 20q13.2 is common in breast cancer, correlates with poor
      prognosis, and may reflect location of an important oncogene. Recently, other
      regions along 20q were also found to undergo amplification. Here, amplification
      levels and patterns of co-amplification were analyzed by interphase fluorescence
      in situ hybridization at 14 loci along 20q in 146 uncultured breast carcinomas
      and 14 cell lines. Three regions were independently amplified in uncultured
      tumors: RMC20C001 region at 20q13.2 (highly amplified in 9.6% of the cases),
      PTPN1 region 3 Mb proximal (6.2%), and AIB3 region at 20q11 (6.2%). Co
      amplifications involving two or three of these regions were seen in 11 of the 19
      highly amplified tumors. The results suggest that three distinct nonsyntenic
      regions along 20q may be important and that complex chromosomal rearrangements
      underlie their frequent co-amplification in breast cancer.

PMID- 8758910
TI  - Hybrid selection of transcribed sequences from microdissected DNA: isolation of
      genes within amplified region at 20q11-q13.2 in breast cancer.
AB  - In human breast carcinomas, increased copy number of DNA sequences derived from
      the long arm of chromosome 20 (20q) has been commonly observed by both chromosome
      microdissection and comparative genomic hybridization. This chromosomal region is
      likely to contain one or more genes that are the biological targets of this
      amplification event. We describe here the utilization of a chromosome
      microdissection-hybrid selection strategy to isolate transcribed sequences from
      microdissected homogeneously staining regions encompassing 20q. Using this
      strategy, we have isolated three novel amplified genes (termed AIB1, AIB3, and
      AIB4) from a cDNA library constructed from the 20q amplified breast cancer cell
      line BT-474. These three genes were mapped to 20q11 (AIB3 and AIB4) and 20q12
      (AIB1) by fluorescence in situ hybridization. Our results indicate an unsuspected
      complexity to the amplification pattern of 20q in breast cancer and provide
      probes that will be useful for further characterization of tumor specimens.

PMID- 8758911
TI  - Binding characteristics of seven inhibitors of human aromatase: a site-directed
      mutagenesis study.
AB  - Aromatase, a cytochrome P450, catalyzes three consecutive hydroxylation reactions
      converting C19 androgens to aromatic C18 estrogenic steroids. In this study,
      eight human aromatase mutants (I133Y, I133W, F235L, I395F, I474Y, I474W, I474M,
      and I474N) were prepared to evaluate the active site and a proposed hydrophobic
      pocket of the enzyme that exists in an aromatase model based on the X-ray
      structure of cytochrome P450cam. In addition, the binding characteristics of
      three steroidal inhibitors [4-hydroxyandrostenedione, 7alpha-(4'-amino)phenylthio
      1,4-androstandiene-3,17-dione, and bridge (2,19-methyleneoxy)androstene-3,17
      dione (MDL 101,003)] and four nonsteroidal inhibitors [aminoglutethimide, CGS
      20267, ICI D1033, and vorozole (R83842)] were investigated through inhibitory
      profile studies on the eight new and three previously generated mutants (P308F,
      D309A, and T310S). The latter analyses have provided a molecular basis regarding
      how seven aromatase inhibitors with different structures bind to the active site
      of aromatase.

PMID- 8758912
TI  - Proton nuclear magnetic resonance spectroscopy reveals cellular lipids involved
      in resistance to adriamycin and taxol by the K562 leukemia cell line.
AB  - Proton nuclear magnetic resonance spectroscopy was performed on whole cells to
      study lipids and metabolites in Adriamycin- and Taxol-resistant K562 cells
      expressing multidrug resistance (MDR) and their sensitive counterparts. With one
      dimensional spectra, both resistant cell lines showed lower fatty acid
      methylene:methyl ratios and higher choline:methyl ratios than sensitive cells.
      Using two-dimensional COSY spectra, a decrease in the glutamine content was
      evidenced in resistant cells. When these cells were maintained in culture medium
      without the drug, the fatty acid signals were partially recovered. Adriamycin
      resistant K562 cells were also treated for 4 days with a high dose of verapamil,
      a MDR-reversing agent. The nuclear magnetic resonance spectra of verapamil
      treated cells also showed partial recovery of fatty acid signals. These results
      could be paralleled with the reversion of the resistant phenotype, as evidenced
      by measuring the inhibiting concentration of Adriamycin and vinblastine in
      K562adr cells cultured without the drug or after short-term exposure to
      verapamil. Conversely, P-glycoprotein and mRNA expression and DNA amplification
      of the mdr gene were not modified when compared to resistant cells, suggesting
      that the MDR phenotype could be partially reversed independently of the mdr gene
      amplification and expression. These results demonstrate the role of lipids in the
      resistance phenomenon.

PMID- 8758913
TI  - Quantitative differences in GlcNAc:beta1-->3 and GlcNAc:beta1-->4
      galactosyltransferase activities between human colonic adenocarcinomas and normal
      colonic mucosa.
AB  - The activities of GlcNAc:beta1-->3 and GlcNAc:beta1->4 galactosyltransferases in
      normal human colonic mucosa and well or moderately differentiated colonic
      adenocarcinomas and their enzyme-kinetic characteristics were investigated. After
      UDP-[3H]galactose and N-linked type monoantennary oligosaccharides GlcNAc beta1-
      >2Man alpha1-->3(6)Man beta1-->4GlcNAc) had been incubated with microsome
      fractions prepared from these tissues, the synthesized [3H]galactose-labeled
      oligosaccharides were analyzed by Ricinus communis agglutinin-I agarose
      chromatography, Streptococcus 6646K beta-galactosidase, Gal beta1-->4-specific
      diplococcal beta-galactosidase, and Gal beta1-->3GlcNAc-specific lacto-N
      biosidase digestion. The beta-galactosyltransferases from normal mucosa
      synthesized both type 1 and type 2 chains at comparable levels, whereas those
      from adenocarcinomas predominantly synthesized type 2 chains. To our knowledge,
      this is the first quantitative estimation of GlcNAc:beta1-->3
      galactosyltransferase activity toward N-linked sugar chains. Furthermore, we
      compared the two galactosyltransferase activities in 10 normal mucosa and
      adenocarcinoma samples and found that while there existed similar levels of
      GlcNAc:beta1-->4 galactosyltransferase activity in normal mucosa and
      adenocarcinomas, GlcNAc:beta1-->3 galactosyltransferase activity apparently
      decreased from 0.67 +/- 0.26 (normal mucosa) to 0.18 +/- 0.11 nmol/min/mg of
      protein (adenocarcinomas). These results are consistent with those of comparative
      structural studies on N-linked sugar chains of carcinoembryonic antigen and its
      normal counterparts and suggest that in the process of differentiated
      carcinogenesis of human colonic tissues, the expression of GlcNAc:beta1-->3
      galactosyltransferase is negatively regulated.

PMID- 8758914
TI  - Enhancement of N-nitrosodiethylamine-initiated hepatocarcinogenesis caused by a
      colchicine-induced cell cycle disturbance in partially hepatectomized rats.
AB  - The effects of a colchicine-induced M-phase block of regeneration after partial
      hepatectomy on early-stage liver carcinogenesis were studied in rats. When
      administered 1 or 3 days after N-diethylnitrosamine initiation and partial
      hepatectomy, colchicine increased the mitotic index of regenerating hepatocytes
      at days 4-6 without evidence of liver cell necrosis. When the protocol was
      combined with a selection procedure (E. Cayama et al., Nature (Lond.), 275: 60
      62, 1978), a significant increase in the size but not number of gamma
      glutamyltranspeptidase-positive foci at week 5 was observed in a colchicine dose
      dependent manner. This was associated with an elevated incorporation of 5-bromo-2
      deoxyuridine into the gamma-glutamyltranspeptidase-positive cells. In a longer
      term experiment, the numbers, sizes, and 5-bromo-2-deoxyuridine labeling index of
      persistent nodules were increased significantly in colchicine-treated rats at
      week 9. This was associated with significant increases in the incidences and
      numbers of hepatocellular carcinomas at week 42. The above results raise the
      interesting possibility that a cell cycle disturbance in the early stage of liver
      carcinogenesis provides a persisting growth advantage for initiated cells,
      resulting in enhanced growth of foci and persistent nodules that evolve into
      hepatocellular carcinomas.

PMID- 8758916
TI  - Breast cancer growth is inhibited by vasoactive intestinal peptide (VIP) hybrid,
      a synthetic VIP receptor antagonist.
AB  - Breast cancer vasoactive intestinal peptide (VIP) receptors were characterized.
      Using in vitro autoradiographic techniques, 125I-labeled VIP bound with high
      affinity to breast biopsy sections. 125I-labeled VIP bound specifically to give
      breast cancer cell lines examined using receptor-binding techniques. Specific
      125I-labeled VIP binding to MDA-MB-231 cells was inhibited with high affinity by
      VIP and pituitary adenylate cyclase-activating polypeptide (IC50, = 2 nM) and
      with moderate affinity by the VIP hybrid (IC50 = 0.5 microM). VIP elevated the
      cAMP in a dose-dependent manner, and VIP hybrid (10 microM) inhibited the
      increase in cAMP caused by VIP. Using Northern blot analysis, VIP (10 nM)
      stimulated c-fos and c-myc mRNA, and the increase caused by VIP was reversed by
      the VIP hybrid. The VIP hybrid inhibited breast cancer growth in vitro and in
      vivo using nude mice bearing breast cancer xenografts. These data suggest that
      the VIP hybrid is a breast cancer VIP receptor antagonist.

PMID- 8758915
TI  - Mitogen-activated protein kinase (MAPK) activation by butylated hydroxytoluene
      hydroperoxide: implications for cellular survival and tumor promotion.
AB  - The mitogen-activated protein kinase (MAPK) cascade plays an important role in
      carcinogenic development. Herein, we show that the skin tumor promoter butylated
      hydroxytoluene hydroperoxide (BHTOOH) stimulates a rapid and potent (14- to 20
      fold) activation of extracellular signal-regulated kinase (ERK) in vivo and in
      cultured mouse keratinocytes. BHTOOH also moderately (5-fold) activated c-jun-N
      terminal kinase, and 38-kDa MAPK-related protein in these same cells. N
      acetylcysteine and o-phenanthroline abolished ERK activation by BHTOOH,
      consistent with a requirement for metal-dependent formation of reactive
      intermediates. Indeed, 4-CD3-BHTOOH, an analogue that generates less of the
      metabolite BHT-quinone methide (2,6-di-tert-butyl-4-methylene-2,5
      cyclohexadienone) and fewer tumors in vivo, accordingly exhibited diminished
      potency for activating ERK. ERK activation by BHTOOH was inhibited by suramin,
      and by expression of dominant-negative Ras-N-17 in PC12 cells, suggesting overlap
      between the pathways for BHTOOH and growth factor signaling. Induction of MAPK
      dependent genes c-fos and MAPK phosphatase-1 by BHTOOH was also blocked by Ras-N
      17 expression. Moreover, expression of Ras-N-17 or kinase-defective MAPK kinase
      (MEK) diminished cell survival following BHTOOH exposure. Similarly, pretreatment
      with suramin or the MEK inhibitor PD098059 also potentiated the toxicity of
      BHTOOH. On the other hand, expression of constitutively active MEK enhanced cell
      survival. Thus, we demonstrate that the MAPK cascade is critical to the cellular
      response to BHTOOH. This study suggests a functional role for MAPK activation in
      tumor promotion stimulated by oxidants and other agents.

PMID- 8758917
TI  - Lack of a role of glutathione in cellular nonenzymatic activation of BMS-181174,
      a novel analogue of mitomycin C.
AB  - Recent studies, using a cell-free system, have suggested that thiol-dependent
      nonenzymatic bioactivation may be responsible for the superior antitumor activity
      of the mitomycin C analogue BMS-181174 [N-7-[2-(4
      nitrophenyldithio)ethyl]mitomycin C] when compared to the parent compound. If
      operational in tumor cells, this pathway could have enormous clinical
      implications since tumor cell resistance to a variety of anticancer agents is
      often associated with increased glutathione (GSH) levels and BMS-181174 may be
      used to reverse this mechanism of resistance. The present study was undertaken to
      determine the role of GSH in cellular activation of BMS-181174 using a pair of
      well-characterized human bladder cancer cells (J82 and SCaBER) as a model. A 20-h
      pretreatment of J82 and SCaBER cells with a nontoxic concentration of D,L
      buthionine-S,R-sulfoximine (BSO) caused about 80-88% reduction in cellular GSH
      levels. Surprisingly, the sensitivity of both cells to BMS-181174 was increased,
      not reduced, by BSO-induced GSH depletion. On the other hand, the cytotoxicity of
      BMS-181174 was significantly reduced in both cells by a 4-h pretreatment with 1
      mM GSH. Like BSO, a 4-h pretreatment with another thiol compound (cysteine)
      resulted in a statistically significant sensitization of both cells to BMS
      181174. Cellular GSH levels were not affected in either of the cell lines by
      pretreatment with GSH or cysteine. In conclusion, the results or the present
      study argue against a role of GSH in cellular nonenzymatic activation of BMS
      181174 in J82 and SCaBER cells.

PMID- 8758918
TI  - Inhibition of growth of human tumor cell lines in nude mice by an antisense of
      oligonucleotide inhibitor of protein kinase C-alpha expression.
AB  - A 20-mer phosphorothioate oligodeoxynucleotide (ISIS 3521) designed to hybridize
      sequences in the 3'-untranslated region of human protein kinase C-alpha (PKC
      alpha) mRNA has been shown to inhibit the expression of PKC-alpha in multiple
      human cell lines. In human bladder carcinoma (T-24) cells, inhibition of PKC
      alpha was both concentration dependent and oligonucleotide sequence specific.
      ISIS 3521 had a IC50 of 50-100 nM for PKC-alpha mRNA reduction and was without
      effect on the expression of other members of the PKC family of genes (PKC-eta and
      zeta). Toxicity studies in mice revealed that the oligodeoxynucleotide was well
      tolerated at repeat doses of 100 mg/kg i.v. for up to 14 days, with no acute
      toxicity apparent. The oligodeoxynucleotide was found to also inhibit the growth
      of three different human tumor cell lines, the T-24 bladder, human lung carcinoma
      (A549), and Colo 205 colon carcinoma grown in nude mice. The inhibition was dose
      dependent with ID50 values for the growth inhibition between 0.06 and 0.6 mg/kg
      daily when given i.v., depending on the cell line examined. Three control
      phosphorothioate oligodeoxynucleotides not targeting human PKC-alpha were without
      effect on the growth of the tumors at doses as high as 6 mg/kg. Recovery of ISIS
      3521 from tumor tissue and resolution by capillary gel electrophoresis revealed
      that 24 It after the final dose of oligodeoxynucleotide, intact, full-length 20
      mer material was present as well as some apparent exonuclease degradation
      products (e.g., n-1 and n-2 mers). These studies demonstrate the in vivo
      antitumor effects of an antisense oligodeoxynucleotide targeting PKC-alpha and
      suggest that this compound may be of value as a chemotherapeutic agent in the
      treatment of human cancers.

PMID- 8758919
TI  - Antibody penetration of tumor GS-7 xenografts in nude mice: a model for mucinous
      adenocarcinoma of the colon.
AB  - A new cell line derived from a human adenocarcinoma of the colon, GS-7, was
      propagated as a s.c. tumor in nude mice. This tumor histologically is a mucinous
      adenocarcinoma (also designated mucoid or colloid) with characteristic large
      mucin pools that are not lined by an epithelial layer but may contain scattered,
      randomly distributed cancer cells. Ten to 20% of human colorectal adenocarcinomas
      are of this histological type, but rapidly growing xenografts with this histology
      have been rarely used experimentally. This tumor, therefore, constitutes a useful
      model for similar human tumors. The mucin pools contain large amounts of
      carcinoembryonic antigen and tumor-associated glycoprotein 72, and the cells
      express epithelial glycoprotein 2 on their surface. The ability of antibodies
      injected i.v. to penetrate this tumor was investigated, using both biotinylated
      and radioiodinated antibodies (Abs). The results demonstrate that Abs can
      effectively penetrate the mucin pools, and that large amounts of Ab can localize
      there. This tumor type may have advantages as a target for certain forms of
      experimental immunotherapy.

PMID- 8758920
TI  - NKR-P1+ cells localize selectively in Rat 9L gliosarcomas but have reduced
      cytolytic function.
AB  - To better understand immune responses to brain tumors and to develop possible
      approaches for immunotherapy, we have investigated the leukocyte populations
      infiltrating the rat 9L gliosarcoma. By immunocytochem-ical analyses of the cells
      infiltrating the tumor, we observed a substantial number of cells expressing
      natural killer cell receptor protein 1 (NKR-P1), a marker expressed only on rat
      lymphocytes capable of non-MHC-restricted cytotoxicity. Previous investigations
      have determined the existence of three populations of NKR-P1+ lymphocytes in
      normal rats, including NKR-P1bright/T-cell receptor (TCR)-/CD3-/CD5-
      (approximately 5-15%), NKR-P1dim-/TCRalphabeta+/CD3+/CD5+ (approximately 1-5%),
      and NKR-P1dim/TCRgammadelta+/CD3+/CD5+ (approximately 0.5-2%). By one-parameter
      flow cytometry, it was determined that NKR-P1+ cells constituted 30-60% of the
      lymphocytes in 9L tumors. Among splenic lymphocytes or peripheral blood
      leukocytes, NKR-P1bright cells are 1.5-4.5 times more numerous than NKR-P1dim
      cells. In striking contrast, NKR-p1dim cells were 4-5 times more numerous than
      NKR-P1bright cells among lymphocytes isolated from 9L tumors. Using quantitative
      analyses of laser confocal microscopic scans, we determined that NKR-P1dim cells
      were approximately 4 times as numerous as NKR-P1bright cells in situ, confirming
      flow cytometric findings. By two-color now cytometric analyses, it was observed
      that approximately 5-10% of the cells were NKR-p1bright/CD5-/TCR-, a phenotype
      representative of NK cells. Also, approximately 11-25% of the cells were NKR
      P1dim/CD5+/TCR+ cells, corresponding to the T-cell subset with non-MHC-restricted
      lytic function. In addition, we observed a cell population among 9L-derived
      lymphocytes with a NKR- p1dim/CD5-/TCR- phenotype (approximately 15-25%). Cells
      of this phenotype have not been reported previously, and most likely represent NK
      cells down-modulated for expression of NKR-P1. Alternatively, they might
      represent cells of unknown origin or cells down-modulated for expression of T
      cell markers in the microenvironment of 9L tumors. We also compared the lytic
      capacity of NKR-P1+ populations derived from normal animals and from 9L
      gliosarcomas. In these experiments, it was determined that, although cells
      isolated from 9L tumors had some capacity to lyse tumor target cells, they were
      clearly less efficient than cells isolated from normal splenocytes. Cumulatively,
      these data suggest that there is selective localization of cells capable of
      mediating antitumor responses in 9L, but that tumor-associated factors may down
      regulate their function and expression of NKR-P1.

PMID- 8758921
TI  - Specific monoclonal antibodies against leukocyte-restricted cell surface molecule
      CD43 react with nonhematopoietic tumor cells.
AB  - CD43 is the major sialoglycoprotein found on the surface of cells of hemopoietic
      origin. Because CD43 is a typical member of the surface mucins, molecules that
      play a relevant role in tumor progression, we have addressed the expression of
      CD43 in nonhematopoietic tumor cells. For this purpose, we have tested a broad
      panel of anti-CD43 antibodies on tumors of different embryonic origins. Of the 17
      anti-CD43 mAbs used, 9 reacted with leukocytes in paraffin-fixed formalin
      embedded lymph node tissues. Two mAbs, BS1 and L10, stained 24 out of 31 (78%)
      nonhematopoietic tumors analyzed; ie., some tumors were positive for both
      antibodies, and others were positive for either L10 or BSL We have also found
      reactivity of these two anti-CD43 mAbs in 13 out of 20 metastases studied.

PMID- 8758922
TI  - Telomerase activity in oral leukoplakia and head and neck squamous cell
      carcinoma.
AB  - The expression of telomerase, a ribonucleoprotein complex, is necessary to
      overcome cellular senescence, and it is associated with immortal cells and
      cancer. However, its role in precancerous lesions such as oral leukoplakias is
      less known. The purpose of this study is to investigate the presence of
      telomerase activity in oral leukoplakia and the relationship between the enzyme
      and multistep tumorigenesis. Telomerase activity was detectable in 14 of 16 human
      head and neck squamous cell carcinomas and 10 of 26 oral leukoplakia tissues. We
      also showed that the expression of telomerase in the premalignant lesions was
      associated with phenotypic progression, the degree of dysplasia. These results
      indicate that telomerase is activated frequently during the late stage of oral
      premalignancy and may play a crucial role in head and neck squamous cell
      carcinogenesis.

PMID- 8758923
TI  - Microsatellite analysis of endometriosis reveals loss of heterozygosity at
      candidate ovarian tumor suppressor gene loci.
AB  - Endometriosis is a very common gynecological condition in which tissue similar to
      endometrium proliferates at sites outside the uterine cavity, most commonly the
      ovary. Although it generally remains a benign condition, malignant transformation
      has been documented. and it is commonly found in association with endometrioid
      subtype ovarian cancer. Tumor suppressor genes are commonly altered in ovarian
      cancers, and the development of endometriosis may involve mutations in the same
      class of genes. We have investigated this possibility by examining DNA from 40
      cases of endometriosis for clonal status, alterations in TP53 and RASK, and
      allelic losses at candidate ovarian tumor suppressor loci on chromosome arms 6q,
      9p, l1q, 17p, l7q, and 22q. The majority of endometriotic cysts were monoclonal,
      but interestingly, 8 of 10 normal endometrial glands were also monoclonal,
      demonstrating that both are able to develop from a single progenitor cell. No
      mutations were detected in TP53 or RASK. Loss of heterozygosity (LOH) was
      detected on chromosomes 9p (18%), 1lq (18%), and 22q (15%). In total, 11 of 40
      (28%) cases demonstrated LOH at one or more of these loci. This study, which is
      the first to report LOH in endometriosis, supports the notion that tumor
      suppressor gene inactivation may play a role in the development of at least a
      subset of cases.

PMID- 8758924
TI  - Flk-1 as a target for tumor growth inhibition.
AB  - A number of growth factor receptor tyrosine kinases have been implicated in
      angiogenesis, including epidermal growth factor receptor, fibroblast growth
      factor receptor, platelet-derived growth factor receptor, Flk-1/KDR, Flt-1, Tie
      1, and Tek/Tie-2. Flk-1/KDR, a receptor for vascular endothelial growth factor
      (VEGF), is expressed exclusively in endothelial cells. Using dominant-negative
      methods, Flk-1 was shown to play a role in angiogenesis and the growth of a
      variety of tumor types. Because of this, a drug discovery effort was established
      to identify Flk-1 kinase inhibitors. For initial screening, an ELISA in, a 96
      well format was used to measure VEGF-induced Flk-1 tyrosine phosphorylation in
      whole cells. Compounds that inhibited ligand-induced receptor autophosphorylation
      were confirmed by antiphosphotyrosine immunoblotting. Inhibition of VEGF
      stimulated DNA synthesis in human endothelial cells was also assessed. Inhibitors
      were further evaluated for their effects on vessel formation using the
      chorioallantoic membrane assay. Using these methods, antiangiogenesis compounds
      that inhibit Flk-1 tyrosine kinase activity, endothelial cell mitogenesis, and
      blood vessel formation in the chorioallantoic membrane assay have been found.

PMID- 8758925
TI  - Accelerated disappearance of melanocytes in bcl-2-deficient mice.
AB  - Follicular melanocytes in bcl-2(-/-) mice have been reported to turn gray during
      the second hair cycle. Light microscopic analysis revealed that about half of bcl
      2(-/-) mouse hair shafts had no detectable melanin granules after the second hair
      follicle cycle, but the remaining hair appeared to be pigmented normally. After
      depilation to induce new anagen hair, more than 97% of the hair shafts did not
      have visible melanin granules in bcl-2(-/-) mice, whereas 100% of the hair shafts
      in bcl-2(+/+) mice were pigmented. In bcl-2(+/+) mice, dopa-positive melanocytes
      appeared on day 4 after depilation, whereas bcl-2(-/-) mice developed few dopa
      positive melanocytes after depilation, as assessed by light and electron
      microscopic observation. bcl-2(-/-) mouse hair in the second hair cycle contained
      about 60-70% less melanin than normal mouse hair, and newly generated bcl-2(-/-)
      mouse hair after depilation contained a level of melanin as low as that of albino
      mouse hair. These observations suggest that the expression of bcl-2 might be
      essential for melanocyte maintenance after the second hair cycle.

PMID- 8758926
TI  - A brief staurosporine treatment of mitotic cells triggers premature exit from
      mitosis and polyploid cell formation.
AB  - At any point during the progression of many tumor types, cells can develop a
      hyperploid DNA content. Hyperploid tumors are significant more aggressive, with a
      higher growth rate and a poor patient prognosis. Yeast genetics have implicated
      three important genes involved in DNA ploidy changes: cdc2, cyclin b, and a
      specific inhibitor of the p34(cdc2)/cyclin B kinase, rum1. Mutations in these
      genes uncoupled the dependence mitosis on DNA replication in the fission yeast,
      Saccharomyces pombe. It was proposed that the inactivation of the mitotic kinase
      complex, p34(cdc2)/cyclin B, induces a G(1), state wherein the cells re-replicate
      their DNA without an intervening mitosis. We show in this report that treatment
      of only M phase-arrested mouse cells, with the protein kinase inhibitor
      staurosporine, induced polyploidy. Nocodazole-arrested metaphase FT210 cells were
      pulsed with 100 ng/ml of staurosporine for 1 h. This 1-h treatment results in the
      inhibition of the mitotic p34(cdc2) kinase. The inhibition of the mitotic kinases
      leads to a reduction in the histone H1 and H3 mitotic-associated
      phosphorylations, chromosome decondensation and nuclear membrane reformation.
      When released into normal growth medium, these cells are reset to a G(1)state, re
      replicate their DNA without completing mitosis, and become octaploid.

PMID- 8758927
TI  - Human breast cancer progression can be regulated by dominant trans-acting factors
      in somatic cell hybridization studies.
AB  - Human breast cancer is often characterized by a progression to an ER (estrogen
      receptor)-negative, estrogen-independent, antiestrogen-resistant, EGFR (epidermal
      growth factor receptor)-positive, and highly metastatic phenotype. The molecular
      and biochemical mechanisms behind this progression are not well defined. Most
      studies of breast cancer have focused on one or another aspect or this
      progression but have not found a common pathway. By constructing stable and
      complete human-human somatic cell fusions between a highly metastatic,
      undifferentiated, ER-negative line of melanoma lineage and the estrogen
      dependent, ER-positive MCF-7 line, this study produced hybrids that were ER
      negative, highly expressive of EGFR, estrogen independent, estrogen unresponsive,
      fully tumorigenic, and highly metastatic. ER negativity was on the basis of
      complete suppression of ER transcription as evidenced by Northern blot analysis
      and nuclear run-on assay, not on the basis of gene rearrangement. EGFR positivity
      was not due to gene amplification or rearrangement but rather to increased EGFR
      transcription. Mechanisms, including ras activation, fibroblast growth factor 4
      expression, and human DNA methyltransferase activation causing ER promoter
      methylation, which are respectively known to induce estrogen-independent growth,
      induce spontaneous metastasis, and decrease ER levels in breast carcinoma
      experimentally, were not mechanisms operating in the hybrids. This model
      demonstrates that many of the common denominators of human breast carcinoma
      progression can be regulated by dominant trans-acting factors.

PMID- 8758928
TI  - Combination of a potent 20-epi-vitamin D3 analogue (KH 1060) with 9-cis-retinoic
      acid irreversibly inhibits clonal growth, decreases bcl-2 expression, and induces
      apoptosis in HL-60 leukemic cells.
AB  - All-trans retinoic acid (RA) is the first highly effective differentiation
      inducing agent for remission induction in patients with acute promyelocytic
      leukemia. However, remissions are short-lived because the treatment fails to
      induce complete differentiation and fails to eradicate the malignant clone. To
      eliminate rapidly the malignant clone, in analogy with aggressive chemotherapy,
      the combination of potent differentiation- and apoptosis-inducing drugs working
      through different receptors and signal pathways may be useful. The active form of
      vitamin D3 (1,25-dihydroxyvitamin D3; 1,25(OH)2D3) inhibits proliferation and
      induces differentiation of myeloid leukemic cells. The 9-cis-RA, unlike all-trans
      RA which binds only retinoic acid receptors, is a high affinity ligand for both
      retinoic acid receptors and retinoid X receptors. The aim of this study was to
      evaluate the therapeutic potential of combining a vitamin D(3) analogue, 20-epi
      22-oxa-24a,26a,27a-tri-homo-1alpha,25(OH) 2D, (KH 1060), which belongs to the
      family of potent 20-epi-1,25(OH),D3 analogues, with 9-cis-RA by assessing their
      effects on the proliferation, differentiation, and apoptosis of the human
      leukemia cell line HL-60 in vitro. Our data show that KH 1060 alone is a very
      potent inhibitor of clonal proliferation of HL-60, but this effect is reversible,
      and that 9-cis-RA alone is a weak inhibitor of clonal proliferation of HL-60
      cells. In contrast, the combination of KH 1060 and 9-cis-RA synergistically and
      irreversibly inhibited the clonal proliferation of HL-60 cells and induced
      apoptosis, as detected by morphological changes and DNA fragmentation. This
      combination also affected the expression of apoptosis-related genes. The bcl-2
      protein became nearly undetectable, and expression of bax protein increased
      slightly (the bax:bcl-2 ratio was 14-fold higher than in untreated cells).
      Differentiation of treated HL-60 cells was assessed by their ability to produce
      superoxide, as measured by reduction of nitro blue tetrazolium, positive staining
      for alpha-naphthyl acetate esterase, phagocytosis, morphology, and analysis of
      membrane-bound differentiation markers with two-color immunofluorescence.
      Treatment with the combination of KH 1060 and 9-cis-RA was a potent inducer of
      differentiation of HL-60, with the cells developing a myelomonocytic phenotype.
      In summary, our data demonstrate that the combination of both KH 1060 and 9-cis
      RA irreversibly and synergistically inhibited clonal growth, induced
      differentiation and apoptosis of HL-60 cells concomitantly with a very marked
      decreased expression of bcl-2, and increased the bax:bcl-2 ratio. This drug
      combination may have important therapeutic significance.

PMID- 8758929
TI  - Transfection of glutathione S-transferase (GST)-pi antisense complementary DNA
      increases the sensitivity of a colon cancer cell line to adriamycin, cisplatin,
      melphalan, and etoposide.
AB  - The goal of this study was to demonstrate that glutathione S-transferase (GST)-pi
      is directly involved in the intrinsic and acquired resistance of cancer cells to
      anticancer drugs. To this end, GST-pi antisense cDNA was transfected into the
      cultured human colon cancer cell line M7609, which expresses an innately high
      level of GST-pi and shows intrinsic drug resistance, and into an M7609 strain
      with acquired resistance to Adriamycin (ADR;i.e., M7609/ADR cells). The changes
      in the sensitivity of these transfectants to various anticancer drugs were
      investigated. The intracellular concentrations of GST-pi in M7609/anti-1 cells
      and M7609/anti-2 cells, two clones that were established by transfection of GST
      pi antisense cDNA into M7609 cells, were decreased to approximately half of those
      detected in the parent cells (M7609) and in the control cells transfected with
      vector alone (M7609/pLJ). The sensitivities of the antisense transfectants in
      relation to ADR, cisplatin, melphalan, and etoposide were increased -3.3-fold,
      2.3-fold, 2.2-fold, and 2.1-fold, respectively, compared with those of M7609 and
      M7609/pLJ. On the other hand, the sensitivities of the antisense transfectants to
      Taxol, vincristine, 5-fluorouracil, and mitomycin C were not significantly
      changed. Similarly, the transfection of antisense cDNA into M7609/ADR cells
      resulted in the reduction of intracellular GST-pi concentration (by about half)
      and an increased sensitivity to ADR (4.4-fold), but no increase in 5-fluorouracil
      sensitivity. Thus, GST-pi is considered to be a multidrug resistance factor that
      is responsible for both the intrinsic and acquired resistance of cancer cells to
      anticancer drugs such as ADR, cisplatin, melphalan, and etoposide.

PMID- 8758930
TI  - Inhibition of proliferation and clonal growth of human breast cancer cells by
      interleukin 13.
AB  - We tested the influence of recombinant human interleukin (rhIL)-l3 and rhIL-4 on
      clonal growth of human breast cancer cell lines. rhIL-13 and rhIL-4 inhibited
      clonal growth of three of nine lines to approximately 50% of controls (ED50, 0.5
      ng/ml). rhIl-13 reduced [3H]thymidine incorporation in all three cell lines: two
      showing a minor (84% and 83% of controls) and one showing a major response (25%
      of control). Both cytokines markedly reduced serum-induced G(0/1) exit
      (approximately 25% versus 60%). 125I-labeled interleukin (IL) 13 binding assays
      revealed high-affinity binding sites for IL-13 on two of the three responding
      cell lines (KD approximately 60 pM). (Y124D)IL-4 effectively antagonized all
      effects of rhIl-13 and rhIL-4, arguing for shared receptor components between
      them. However, neither rhIl-4 nor (Y124D) IL-4 could displace 125I-labeled IL-13
      from binding, although unlabeled rhIL-13 effectively did so. Using reverse
      transcription-PCR, we studied the expression of the common gamma chain (gammac)
      in responding cell lines, putatively being shared between IL-4 receptor and IL-13
      receptor; none of the three cell lines express gammac. In conclusion, we
      demonstrate antiproliferative effects of IL-4 and IL-13 on carcinoma cells which
      express IL-13 binding sites without participation of gammac.

PMID- 8758931
TI  - Activation of Src kinases p53/56lyn and p59hck by p210bcr/abl in myeloid cells.
AB  - Chronic myeloid leukemia is characterized by the Philadelphia (Ph1) translocation
      t(9;22) that generates a hybrid gene, bcr/abl, translated to a Mr210,000 tyrosine
      kinase (p210bcr/abl) with transforming activity for hematopoietic cells.
      Hematopoietic cell transformation by p2l0bcr/abl seems to involve activation of
      the Ras signaling pathway by at least two different signaling intermediates,
      growth factor receptor-bound protein 2 and Src homology and collagen protein, but
      additional signaling proteins are likely to be required as well. In an effort to
      identify additional phosphoproteins activated by p210bcr/abl, we studied the
      murine, interleukin 3-dependent, myeloid cell line, 32D, and a bcr/abl
      transfected, factor-independent subline, 32Dp210. The analysis of whole-cell
      lysates of 32D and 32Dp210 cells showed that several proteins with a molecular
      weight of Mr50,000-60,000 were phosphorylated on tyrosine residues in 32Dp210
      cells. Because Src family kinases have an apparent molecular weight of Mr50,000
      60,000, we asked whether they could become activated by p2l0bcr/abl. Two Src
      family kinases, p53/56lyn and p59hck, showed a severalfold higher phosphokinase
      activity in 32Dp210 cells than in 32D cells. Coimmunoprecipitation experiments
      with anti-Lyn, anti-Hck, and anti-Abl antibodies demonstrated an intracellular
      association of p210bcr/abl with p53/56lyn and p59hck. Moreover, the phosphokinase
      activity of p53/56lyn was higher in bcr/abl-positive myeloid cell lines (K562,
      BV173, and LAMA84) than in the bcr/abl-negative myeloid cell line JOSK-M. In
      conclusion, the results show that p210bcr/abl induces the activation of at least
      two Src family kinases, P53/56lyn and p59hck, in myeloid cells. These findings
      extend the range of potential targets of p210bcr/abl that might mediate its
      transforming effects.

PMID- 8758932
TI  - Induction of primary cutaneous melanocytic neoplasms in urokinase-type
      plasminogen activator (uPA)-deficient and wild-type mice: cellular blue nevi
      invade but do not progress to malignant melanoma in uPA-deficient animals.
AB  - Evidence suggests that the plasminogen activators (PAs), in particular urokinase
      type PA (uPA), play a pivotal role in tumor invasion and metastasis. We studied
      the contribution of the PAs to the malignant phenotype through the chemical
      induction of melanocytic neoplasms in uPA-deficient mice. Primary tumors were
      induced and promoted concurrently in 35 uPA-/- deficient and 35 uPA+/+ wild-type
      mice using a single application of 7,12-dimethylbenz(a)anthracene followed by
      repetitive applications of croton oil. Animals were sacrificed at 60-day
      intervals for 1 year. At necropsy, the four largest pigmented lesions in each
      animal were excised, characterized histologically, and evaluated microscopically
      for evidence of invasion. The regional lymph nodes, lungs, and solid abdominal
      visceral organs were sectioned and examined microscopically for evidence of
      metastatic disease. Cellular blue nevi were induced in 100% of uPA-/- and uPA+/+
      promoted animals. Although a reduction in the radial and vertical progression of
      these lesions was noted in the uPA-deficient mice compared with the wild-type
      group, more than 95% of cellular blue nevi induced in both groups of animals
      invaded the underlying tissues. These lesions did not metastasize to the regional
      lymph nodes. Malignant melanoma arose in 5 of 35 (14.3%) of promoted wild-type
      mice. These tumors were locally aggressive, produced tissue-type PA, but were not
      metastatic to the regional nodes, lungs, or abdominal viscera. These results
      indicate that the invasive capability of melanocytic lesions may depend more on
      tissue-type PA than uPA activity. No melanomas were induced in the uPA-/- mice.
      The resistance of the uPA -/- strain to melanoma induction suggests that uPA
      contributes to malignant progression. We propose that the absence of uPA
      negatively affects tumorigenesis by decreasing the liberation and availability of
      growth factors such as basic fibroblast growth factor.

PMID- 8758933
TI  - Inverse association of cell adhesion regulator messenger RNA expression with
      metastasis in human colorectal cancer.
AB  - Alterations in several classes of adhesion molecules have been implicated in the
      progression of colorectal cancer. Cell adhesion regulator (CAR) has been
      identified as a regulator molecule of integrin-dependent cell adhesion. We have
      explored a possible involvement of the CAR gene in colorectal cancer. Reverse
      transcription-PCR revealed that CAR expression was detected in normal colonic
      cells, whereas it was decreased or undetectable in 6 of 13 (46.2%) human colon
      cancer cell lines. To further study the biological significance of CAR expression
      in colon cancer cells, a CAR expression vector was introduced into HT-29 cells,
      in which CAR is not expressed. Adhesion of HT-29 cells to extracellular matrix
      components was up-regulated by the introduction of CAR. In spite of similar
      growth properties with the controls, CAR-transfected HT-29 cells showed a
      significantly reduced spontaneous metastatic potential in nude mice. To determine
      whether these experimental results are of relevance with respect to actual human
      tumors, we investigated CAR expression in 30 surgical specimen pairs of human
      colorectal cancer and adjacent noncancerous tissue using semiquantitative reverse
      transcription-PCR. In 14 of 30 cases (46.7%), CAR expression in cancer was less
      than one-tenth of that in matched noncancerous tissue. The tumor:normal ratio of
      CAR expression was significantly lower in patients with lymph node metastasis
      than in those without it (P < 0.01) and in patients with distant metastasis than
      in those without it (P < 0.05). CAR expression was significantly lower in more
      advanced Dukes' stage tumors (P < 0.05). Our results suggest that down-regulation
      of CAR expression may play an important role in the progression and metastasis of
      colorectal cancer.

PMID- 8758934
TI  - Correspondence re: N-B. Liabakk et al., matrix metalloprotease 2 (MMP-2) and
      matrix metalloprotease 9 (MMP-9) type IV collagenases in colorectal cancer.
      Cancer Res., 56: 190-196, 1966.

PMID- 8758935
TI  - Interaction of P-glycoprotein with protein kinase C in human multidrug resistant
      carcinoma cells.
AB  - Indirect evidence has suggested that P-glycoprotein (P-gp), the multidrug
      transporter, is phosphorylated by protein kinase C (PKC) and that phosphorylation
      modulates its transport function. To address the first premise more directly,
      ie., that P-gp is phosphorylated by PKC, we investigated the interaction between
      P-gp and PKC in sensitive and multidrug resistant MCF-7 and KB human carcinoma
      cell lines. We found that P-gp and PKC were coimmunoprecipitated from the
      multidrug-resistant cell lines MCF-7/AdrR and KB-V-1, using antibodies to either
      protein. The association between the two proteins was enhanced by phorbol 12
      myristate 13-acetate, an analogue of diacylglycerol that induces translocation of
      PKC to the plasma membrane. The anti-P-gp immunoprecipitates contained PKC
      activity as measured by direct phosphorylation reactions. The interaction of PKC
      with P-gp displayed isozyme specificity: PKC-alpha, -beta, gamma, -epsilon, and 
      phi, but not -delta, -mu, -zeta, -lambda, were found to coimmunoprecipitate with
      P-gp. These studies indicate that P-gp closely interacts with PKC and serves as a
      substrate, and that specific isozymes of this kinase may be involved in the
      phosphorylation of the multidrug transporter.

PMID- 8758938
TI  - The semaphorins: a family of axonal guidance molecules?

PMID- 8758936
TI  - Transcriptional activation by p53, but not induction of the p21 gene, is
      essential for oncogene-mediated apoptosis.
AB  - The p53 tumor suppressor limits cellular proliferation by inducing either G1
      arrest or apoptosis, depending on the cellular context. To determine if these
      pathways are mechanistically distinct, we have examined the effects of different
      p53 mutants in p53 null primary mouse embryo fibroblasts. We chose this system as
      it is highly physiological and ensures that the interpretation of the results
      will not be confounded by the presence of endogenous p53 or oncoproteins which
      target p53. Using single cell microinjection assays for both G1 arrest and
      apoptosis, with loss-of-function and chimeric gain-of-function mutants, we have
      demonstrated that transcriptional activation is critical for both processes.
      Replacement of the p53 activation domain with that of VP16, or replacement of the
      p53 oligomerization domain with that of GCN4, reconstituted both G1 arrest and
      apoptosis activities. However, despite the importance of transcriptional
      activation in both processes, the target gene requirements are different. The p21
      cyclin-dependent kinase inhibitor, which has been shown to be a direct target of
      p53 and a component of the radiation-induced G1 arrest response, is dispensable
      for oncogene-induced apoptosis, suggesting that these two p53-dependent
      transcriptional pathways are distinct.

PMID- 8758939
TI  - Chronic NMDA receptor antagonism during retinotopic map formation depresses CaM
      kinase II differentiation in rat superior colliculus.
AB  - We examined the effects of chronic NMDA receptor antagonism on the normal
      postnatal differentiation of calcium- and calmodulin-dependent kinase II (CaM
      kinase II) in the rat superior colliculus. At postnatal day (P) zero, most CaM
      kinase II protein, as well as CaM kinase II activity, was detected in the soluble
      fraction. In vitro phosphorylation of P0 superior colliculus revealed several
      prominent substrates in both the particulate and soluble fractions. At P19 there
      was more particulate enzyme than soluble enzyme, and CaM kinase II activity in
      the particulate fraction was higher than in P0 particulate tissue. Additionally,
      in vitro phosphorylation of P19 superior colliculus revealed many more CaM kinase
      II substrates. Chronic NMDA receptor antagonism with 2-amino-5-phosphonovalerate
      (DL-AP5) caused CaM kinase II to retain many of the characteristics of the enzyme
      found in P0 untreated superior colliculus. In P19 superior colliculus treated
      with LD-AP5 from birth, most of the protein was in the soluble fraction, CaM
      kinase II activity was largely restricted to the soluble fraction, and only a few
      substrates were observed by in vitro phosphorylation. These effects were not
      observed in tissue treated with the inactive isomer, L-AP5. These results suggest
      that synaptic maturation is slowed by antagonism of NMDA receptors during
      retinotopic map formation.

PMID- 8758937
TI  - Distinct domains of hTAFII100 are required for functional interaction with
      transcription factor TFIIF beta (RAP30) and incorporation into the TFIID complex.
AB  - TFIID is the DNA binding component of the RNA polymerase II transcriptional
      machinery and is composed of the TATA binding protein (TBP) and TBP-associated
      factors (TAFIIs). Here we report the characterization of a new human TAF,
      hTAFII100, which is the human homologue of Drosophila TAFII80 and yeast TAFII90.
      hTAFII100 interacts strongly with hTAFII250, hTAFII55 and hTAFII28, less with
      hTAFII20 and hTAFII18, weakly with TBP and not at all with delta NTAFII135 and
      hTAFII30. Deletion analysis revealed that the C-terminal half of hTAFII100, which
      contains six WD-40 repeats, is not required for incorporation into the TFIID
      complex. Our results suggest that hTAFII100 can be divided into two domains, the
      N-terminal region responsible for interactions within the TFIID complex and the C
      terminal WD repeat-containing half responsible for interactions between hTAFII100
      and other factors. An anti-hTAFII100 antibody, raised against a C-terminal
      epitope, selectively inhibited basal TFIID-dependent in vitro transcription and
      the specific interaction between hTAFII100 and the 30 kDa subunit of TFIIF
      (RAP30). We demonstrate that the hTAFII100-TFIIF interaction supports pre
      initiation complex formation in the presence of TFIID. Thus, this is the first
      demonstration that a TAFII functionally interacts with a basal transcription
      factor in vitro.

PMID- 8758940
TI  - Transient colocalization of parvalbumin and calbindin D28k in the postnatal
      cerebral cortex: evidence for a phenotypic shift in developing nonpyramidal
      neurons.
AB  - In the adult rat cerebral cortex the calcium-binding proteins parvalbumin and
      calbindin D28k are present in essentially non-overlapping populations of
      GABAergic interneurons. These proteins follow different developmental patterns in
      the cortex: calbindin D28k-immunoreactive nonpyramidal neurons are abundant until
      the second postnatal week and decrease markedly thereafter; it is at this time
      that parvalbumin immunoreactivity develops in cortical nonpyramidal neurons. To
      determine whether parvalbumin-immunoreactive neurons derive from calbindin D38k
      positive cells we used double-immunofluorescence studies for both calcium-binding
      proteins, together with combined immunocytochemistry for calbindin D28k and in
      situ hybridization for parvalbumin mRNA during postnatal development. Double
      labelled cells were found in all cortical layers between P9 and P21, coinciding
      with the onset of parvalbumin expression. The percentage of colocalization of the
      two calcium-binding proteins depended on the age and layer examined.
      Colocalization reached a peak (80-100%) during the second postnatal week. Double
      labelled neurons were rare in layer V at all ages studied. The present results
      indicate a phenotypic shift during the development of some cortical interneurons
      that halts the expression of calbindin D28k while parvalbumin expression starts.
      These findings agree with lineage analyses reporting that different types of
      nonpyramidal neuron arise from a common progenitor.

PMID- 8758941
TI  - The convergence of axon terminals from the mediodorsal thalamic nucleus and
      ventral tegmental area on pyramidal cells in layer V of the rat prelimbic cortex.
AB  - We investigated the ultrastructural basis of the synaptic convergence of afferent
      fibres from the mediodorsal thalamic nucleus (MD) and the ventral tegmental area
      (VTA) on the prefrontal cortical neurons of the rat by examining the synaptic
      relationships between thalamocortical or tegmentocortical terminals labelled with
      anterograde markers [lesion-induced degeneration or transport of wheat germ
      agglutinin conjugated to horseradish peroxidase (WGA-HRP)] and randomly selected
      unlabelled apical dendrites of layer V pyramidal cells in the prelimbic cortex.
      WGA-HRP-labelled terminals from the VTA ranged in diameter from 0.7 to 2.8 microm
      and established synaptic contacts with large dendritic profiles, i.e. proximal
      segments of apical dendritic shafts and spines from layer V pyramidal cells.
      Symmetrical synapses, i.e. inhibitory synapses, were more often seen than
      asymmetrical ones. Degenerating terminals from the MD formed asymmetrical
      synapses on dendritic spines or occasionally on small dendritic shafts of apical
      dendrites from layer V pyramidal cells, which received tegmentocortical synapses,
      mostly within layer III. Thalamocortical synapses were more distally distributed
      over common apical dendrites than tegmentocortical synapses, although some of
      them overlapped. The numerical density of direct synaptic inputs from the MD and
      VTA was low. These results suggest that fibres from the VTA exert their
      inhibitory effects directly on pyramidal cells in layer V via synaptic junctions
      with apical dendrites of these pyramidal cells, and that the tegmentocortical
      fibres are in an ideal anatomical position to modulate the reverberatory circuits
      between the MD and the prelimbic cortex.

PMID- 8758942
TI  - Interactions between associative synaptic potentials in the piriform cortex of
      the in vitro isolated guinea pig brain.
AB  - The interaction between synaptic potentials generated by the activation of
      separate sets of associative fibres was investigated in the piriform cortex of an
      in vitro isolated guinea pig brain preparation. Restricted regions of the
      piriform cortex served by separate contingents of afferent fibres of the lateral
      olfactory tract were isolated surgically. The activity generated by these patches
      of cortex in response to afferent stimulation propagates to remote cortical
      regions along cortico-cortical associative fibres. Current source density (CSD)
      analysis of field potential laminar profiles evoked by lateral olfactory tract
      stimulation confirmed that the synaptic sinks induced by distinct associative
      fibre contingents converge on the apical dendrites of piriform cortex neurons in
      the superficial lb layer. Pairing between potentials evoked by activation of two
      separate sets of associative fibres resulted in an almost linear summation when
      the two responses coincided. For interstimulus intervals of <100 ms,
      heterosynaptic pairing of independent associative inputs induced a facilitation
      of the conditioned associative potential, which correlated with an increase in
      the associative sink located in layer lb, as demonstrated by CSD analysis. The
      evaluation of the pairing intervals suggests that the heterosynaptic facilitation
      of the conditioned associative potentials may be due to the summation of local
      and remote associative synaptic events. It is concluded that separate associative
      inputs converge on the apical dendrites of piriform cortex pyramidal neurons to
      generate synaptic potentials through the activation of spatially close but
      independent synapses. The role of associative synaptic integration in the
      functional organization of the olfactory cortex is discussed.

PMID- 8758943
TI  - Cortical networks for visual reaching: intrinsic frontal lobe connectivity.
AB  - The anatomical substrates of reaching to visual targets were studied in monkeys
      (Macaca nemestrina) by combining behavioural neurophysiology and neuroanatomy. An
      instructed-delay reaching task was used to characterize the arm-related regions
      of the dorsolateral frontal cortex. This task revealed gradients of signal-, set-
      movement- and position-related activity along the rostrocaudal extent of the
      frontal lobe. The frontal mesial projections to these physiologically defined
      gradients were studied through anatomical methods based on the retrograde
      transport of distinguishable tracers. The tangential distribution of the cells of
      origin of these projections displayed a gradient-like arrangement similar to that
      defined physiologically in their terminal territory. These mesial projections to
      the dorsolateral frontal cortex may therefore be considered part of a cortical
      network wherein connections make only a limited contribution to the integration
      of different sources of information for the control of reaching movements.
      Further combination of such information must occur within each given cortical
      region by intrinsic local connections.

PMID- 8758944
TI  - Glutamate-enriched inputs from the mesopontine tegmentum to the entopeduncular
      nucleus in the rat.
AB  - In order to clarify the origin and to examine the synaptology of the projection
      from the mesopontine tegmentum to the entopeduncular nucleus, rats received
      discrete deposits of anterograde tracers in different regions of the mesopontine
      tegmentum. Anterogradely labelled fibres in the entopeduncular nucleus were
      analysed at the light and electron microscopic levels. To determine the
      neurochemistry of the projection, the distributions of GABA and glutamate
      immunoreactivity in anterogradely labelled boutons in the entopenducular nucleus
      were studied by postembedding immunocytochemistry. The morphological
      characteristics of anterogradely labelled structures were compared to those of
      choline acetyltransferase-immunopositive structures. The anterograde tracing
      demonstrated that the projection to the entopeduncular nucleus arises from the
      area defined by the cholinergic neurons of the pedunculopontine region and from
      the more medial and largely non-cholinergic, midbrain extrapyramidal area. The
      anterogradely labelled terminals formed asymmetrical synaptic contacts with
      dendritic shafts, cell bodies and more rarely spines in the entopeduncular
      nucleus, and they were significantly enriched in glutamate immunoreactivity
      compared to identified GABAergic terminals in the same region. The morphology,
      trajectory and synaptology of the anterogradely labelled fibres showed
      similarities to those of choline acetyltransferase-immunopositive fibres and
      terminals, providing indirect evidence in support of previous suggestions that at
      least part of the projection is cholinergic. The structures postsynaptic to the
      anterogradely labelled boutons also received input from other classes of
      terminals that had the morphological and neurochemical characteristics of boutons
      derived from the neostriatum, globus pallidus and subthalamic nucleus. These
      findings imply that the mesopontine tegmentum sends a projection to the
      entopeduncular nucleus that is heterogeneous with respect to its origin and also
      possibly its neurochemistry. The synaptology of the projection underlies one
      route through which the mesopontine tegmentum can exert effects on movement by
      modulating the direct and indirect pathways of information flow through the basal
      ganglia.

PMID- 8758945
TI  - The glutamatergic innervation of oxytocin- and vasopressin-secreting neurons in
      the rat supraoptic nucleus and its contribution to lactation-induced synaptic
      plasticity.
AB  - The present ultrastructural study analysed the distribution of glutamatergic
      synapses on oxytocin- and vasopressin-secreting neurons in the rat supraoptic
      nucleus (SON) after post-embedding immunogold labelling for glutamate
      immunoreactivity, visible over synaptic-like vesicles, mitochondria and synaptic
      densities. Double labelling for glutamate and GABA showed that putative
      glutamatergic terminals were distinct from GABAergic terminals. In ultrathin
      sections stained for glutamate and either oxytocin or vasopressin, the proportion
      of glutamatergic synapses was similar on oxytocinergic and vasopressinergic
      somata in virgin rats under basal conditions of peptide release as well as in
      lactating rats, in which oxytocin secretion is enhanced. Cross-sectional soma
      areas were significantly increased in lactating rats: oxytocinergic profiles
      were, on average, approximately 40% larger than in virgin rats. However, the
      incidence of axo-somatic glutamatergic synapses (assessed as mean number of
      synapses per 100 microm of plasmalemma or proportion of somatic surface apposed
      to synaptic active zones) did not diminish, indicating that there was a
      compensatory increase of synapses during lactation. Also, we found an increase in
      the number of glutamatergic terminals making synaptic contact simultaneously onto
      two or more oxytocinergic elements in the same plane of section. Our observations
      therefore indicate that SON oxytocinergic and vasopressinergic neurons are
      innervated to a similar extent by a relatively large proportion of glutamatergic
      synapses. They reveal, moreover, that glutamatergic afferents participate in the
      lactation-induced synaptic plasticity of the oxytocinergic system.

PMID- 8758946
TI  - Evidence for an anuran homologue of the mammalian spinocervicothalamic system: an
      in vitro tract-tracing study in Xenopus laevis.
AB  - Evidence is presented for an anuran homologue of the mammalian
      spinocervicothalamic system. In vitro tract-tracing experiments with biotinylated
      dextran amine Xenopus laevis show that ascending spinal fibres from all levels of
      the spinal cord, passing via the dorsolateral funiculus, terminate in a cell area
      ventrolateral to the dorsal column nucleus. This cell area can be considered a
      possible homologue of the mammalian lateral cervical nucleus. After tracer
      applications to the ventral thalamus or to the torus semicircularis (both targets
      for somatosensory projections), the anuran lateral cervical nucleus was
      retrogradely labelled contralateral to the application sites. Tracer applications
      to the dorsolateral funiculus at the obex level and rostral spinal cord resulted
      in labelling of the cells of origin of the spinocervical tract. These were found,
      mainly ipsilaterally, in the ventral part of the dorsal horn, and were rather
      evenly distributed throughout the spinal cord. These data suggest the presence of
      an anuran homologue of the mammalian spinocervicothalamic system. A brief survey
      of the literature shows that such a system is much more common in vertebrates
      than previously thought.

PMID- 8758947
TI  - Regional variation in expression of calbindin and inositol 1,4,5-trisphosphate
      receptor type 1 mRNAs in the cerebellum of the staggerer mutant mouse.
AB  - The Purkinje cells in the staggerer mutant mouse have various cellular
      abnormalities, including reduced cell number, ectopia, smaller size and absence
      of dendritic spines. It is also know that some of these abnormalities exhibit
      regional variations in the cerebellum. In this paper we have investigated
      expression in the staggerer Purkinje cells of the calbindin and inositol 1,4, 5
      trisphosphate receptor type 1 mRNAs by in situ hybridization. Although the
      transcription levels of both mRNAs were significantly reduced compared with the
      wild-type cells, the reduction among the Purkinje cell populations was not even,
      varying greatly from region to region. Purkinje cells with different
      transcription levels were distributed in discrete regions and arranged
      alternately in the mediolateral direction. Moreover, the cell bodies with higher
      transcription levels were larger in size and aligned in a monolayer between the
      granular and molecular layers, whereas those with lower levels were smaller in
      size, fewer in number and dispersed throughout the granular layer. These findings
      suggest that there is a distinct mediolateral heterogeneity in the staggerer
      cerebellum with respect to transcription levels of these Purkinje cell-specific
      molecules, which might correlate with some cytological phenotypes.

PMID- 8758948
TI  - Subthalamic nucleus lesion in rats prevents dopaminergic nigral neuron
      degeneration after striatal 6-OHDA injection: behavioural and immunohistochemical
      studies.
AB  - Several studies have shown that antagonists of N-methyl-D-aspartate receptors
      provide protection of the dopaminergic nigrostriatal pathway in animal models of
      Parkinson's disease. Since the substantia nigra compacta receives a moderate
      glutamatergic innervation from the subthalamic nucleus, we tried to determine
      whether subthalamic nucleus lesion could prevent the toxicity of the selective
      dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA). Experiments were carried out
      on four groups of rats. Group 1 (n = 10) received a unilateral injection of 6
      hydroxydopamine in the striatum and group 2 (n = 10) received kainic acid in the
      subthalamic nucleus. Group 3 (n = 10) received an injection of kainic acid in the
      subthalamic nucleus and 1 week later an injection of 6-OHDA in the striatum.
      Group 4 (n = 5) received the same treatment but kainic acid was replaced by
      saline. Apomorphine induced an ipsilateral rotation in rats of groups 2 and 3 and
      a contralateral rotation in rats of groups 1 and 4. The number of tyrosine
      hydroxylase-immunoreactive cells in the pars compacta of the substantia nigra was
      not significantly decreased on the side ipsilateral to 6-OHDA striatal injection
      in rats of groups 1 and 4. These results show that subthalamic nucleus lesion
      provides neuroprotection of the dopaminergic nigrostriatal pathway against 6-OHDA
      toxicity and opens a new way for slowing or stopping the progression of
      Parkinson's disease.

PMID- 8758949
TI  - Target selectivity and neurochemical characteristics of VIP-immunoreactive
      interneurons in the rat dentate gyrus.
AB  - Vasoactive intestinal polypeptide (VIP) has been shown to be present in a
      morphologically heterogeneous subpopulation of interneurons in the dentate gyrus,
      but the relationship between their input and output characteristics and
      neurochemical features has not been established. Three types of VIP
      immunoreactive cells have been identified on the basis of these criteria: (i)
      cells forming a dense axonal plexus in the hilus have always coexisted with the
      calcium binding protein calretinin (CR), but never with the neuropeptide
      cholecystokinin (CCK). The postsynaptic targets of these VIP-positive cells were
      neurons visualized by immunostaining for substance P receptor, which is known to
      label different hilar non-principal cells. (ii) VIP-immunoreactive basket cells,
      innervating predominantly the somata and proximal dendrites of granule cells,
      were found in the striatum moleculare and stratum granulosum. They contained CCK,
      but not CR. (iii) Cells projecting to the stratum moleculare were found to have
      dendrites and axons restricted to this layer. In 75% of these cells VIP coexisted
      with CR but not with CCK, and they established multiple contacts largely with non
      principal cells. GABA was shown to be present but the calcium-binding proteins
      calbindin D28K and parvalbumin were absent in all three types of VIP-containing
      interneuron. On the basis of these observations we conclude that three different
      types of VIP-positive neuron are present in this area, and are likely to subserve
      different inhibitory functions, cells with a hilar projection as well as those
      projecting to the stratum moleculare may synchronize the activity of hilar and
      other interneurons, or disinhibit granule cells by specific interneuron-to
      interneuron connections. In contrast, basket cells control the activity of
      granule cells directly, via perisomatic inhibition.

PMID- 8758950
TI  - Expression of heat shock protein-70 and limbic seizure-induced neuronal death in
      the rat brain.
AB  - The effect of MK-801, a non-competitive N-methyl-D-aspartate (NMDA) antagonist,
      on the kainic acid-induced expression of the inducible heat shock protein 70 kDa
      (HSP70) and on neuronal death in the rat hippocampus was investigated. HSP70 is
      expressed in approximately 80% of the pyramidal neurons in the CA1 field 1 day
      after kainic acid injection. The majority of these HSP70-immunopositive neurons
      exhibited swelling and a hollow appearance in the perikaryon, indicating that
      they had been injured following kainic acid-elicited limbic seizures. Four days
      after administration of kainic acid, 87% of the pyramidal neurons in the CA1
      field were dead. When a single dose of MK-801 was administered 1 h before kainic
      acid injection, the number of rats suffering with seizures was reduced, the
      severity of limbic seizures was attenuated and seizure onset was delayed. Neither
      HSP70 expression on day 1 nor neuronal loss on day 4 in the CA1 pyramidal cell
      layer was observed in these animals. A considerable number of HSP70
      immunopositive neurons was detected in the dentate hilus, however, and somewhat
      fewer in the CA3a and CA3c subfields on day 1. Severe neuronal damage in these
      regions followed on day 4. Interestingly, little HSP70 expression or neuronal
      loss was observed in the CA3b subfield in these same animals. When a single dose
      of MK-801 was given 4 h after kainic acid treatment, HSP70 expression was
      partially blocked; 18% of neurons expressed HSP70 on day 1 and 37% on day 4 in
      CA1 pyramidal neurons in comparison to the kainic acid controls. About 50%
      neuronal death was detected in the CA1 pyramidal cell layer 4 days after kainic
      acid treatment followed by MK-801. When the animals were treated with MK-801 4 h
      after kainic acid treatment followed by additional daily administration for 3
      days, a negligible number of pyramidal neurons expressed HSP70, and the survival
      of pyramidal cells was significantly increased in the CA1 field. Limbic seizure
      induced HSP70 expression not only indicates neuronal injury in the pyramidal cell
      layer of the hippocampus but also predicts delayed neuronal death, at least in
      the case of the CA1 field of animals that suffered stage IV-V seizures.

PMID- 8758951
TI  - Involvement of gamma and beta actin isoforms in mouse neuroblastoma
      differentiation.
AB  - Two actin isoforms, gamma and beta, are contained within neuroblastoma cells.
      However, the relative amount and distribution of both isoforms within the cells
      are differentially regulated during neurite extension. The proportion of gamma
      actin isoform became about four times greater than that of beta actin during
      neuroblastoma cell differentiation. Additionally, whereas beta actin appears to
      be concentrated in the cell cortex, gamma actin is also present throughout the
      cell body. Upon differentiation, neuroblastoma cells reorganize their actin
      cytoskeleton and gamma actin is induced to polymerize whereas beta actin polymers
      are partially disassembled. Moreover, both actin isoforms are differentially
      distributed within differentiated cells. Thus, gamma actin polymers are located
      both in the soma and proximal regions of extended neurites, whereas beta actin is
      enriched in the terminal tip of the neurites. Our results strongly suggest that
      both actin isoforms are involved in a different way in neuroblastoma cell
      differentiation.

PMID- 8758952
TI  - Autocrine-paracrine regulation of hippocampal neuron survival by IGF-1 and the
      neurotrophins BDNF, NT-3 and NT-4.
AB  - In contrast to sympathetic and sensory neurons in the peripheral nervous system,
      the neurotrophic requirements for neurons in the central nervous system (CNS)
      have not been clearly identified. The inactivation of specific neurotrophic
      factors and their receptors by gene targeting has shown that there are no major
      changes in neuron numbers in the CNS. This suggests an overlap between the action
      of different neurotrophic factors in the brain during development. Here we have
      studied the survival of hippocampal neurons prepared from embryonic rats using
      different culture conditions. Whereas the hippocampal neurons survive well in
      culture when plated at high density, they die at lower cell densities in the
      absence of appropriate neurotrophic factors. Under the latter conditions, both
      insulin-like growth factor-1 (IGF-1) and neurotrophins - brain-derived
      neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) -
      rescued a large proportion of cultured neurons. In addition, hippocampal neurons
      from BDNF knockout mice exhibited enhanced cell death compared with cells from
      wild-type animals. BDNF and IGF-1 both increased the survival of the hippocampal
      neurons lacking BDNF, showing complementary action for these factors in
      supporting survival. Blocking antibodies against NT-3 and IGF-1 decreased
      hippocampal neuron survival at low cell densities, showing autocrine or paracrine
      action of the factors. At higher cell densities, however, the antibodies had no
      effect, demonstrating that there is a sufficient amount of endogenous factors in
      supporting survival. Blocking antibodies against NT-3 and IGF-1 decreased
      hippocampal neurons depend for survival on local neurotrophic factors such as IGF
      1, BDNF and NT-3, which act in an autocrine/paracrine manner. The multifactorial
      support of hippocampal neurons ensures a maximal degree of neuron survival even
      in the absence of an individual factor

PMID- 8758953
TI  - Pain processing in four regions of human cingulate cortex localized with co
      registered PET and MR imaging.
AB  - Neurosurgical and positron emission tomography (PET) human studies and animal
      electrophysiological studies show that part of the anterior cingulate cortex
      (ACC) is nociceptive. Since the contribution of the ACC to pain processing is
      poorly understood, this study employed PET and magnetic resonance (MR) image co
      registration in grouped and individual cases to locate regions of altered
      relative regional cerebral blood flow (rCBF). Seven right-handed, neurologically
      intact males were subjects; each received neuropsychological and pain threshold
      testing. Subjects were scanned during infusion of H2[15O]: four randomized scans
      during innocuous heat stimulation to the back of the left hand and four scans
      during noxious but bearable heat to the same place. The averaged rCBF values
      during innocuous stimuli were subtracted from those during noxious stimuli and
      statistical parametric maps (SPMs) for the group were computed to identify
      regions of altered relative rCBF. Finally, single-subject PET images of elevated
      and reduced rCBF were co-registered with MR images and projected onto
      reconstructions of the medial surface of the hemisphere. The SPM analysis of the
      group showed one site with elevated rCBF in the midcingulate cortex and one in
      the perigenual cortex predominantly contralateral to the side of stimulation.
      There were bilateral sites of reduced rCBF in the cingulofrontal transitional
      cortex and in the posterior cingulate cortex (PCC). Co-registered PET and MR
      images for individuals showed that only one case had a single, large region of
      elevated rCBF, while the others had a number of smaller regions. Six cases had at
      least one significant elevation of rCBF in the right hemisphere that primarily
      involved area 24b'; five of these cases also had an elevation in area 32', while
      the seventh case had elevated rCBF in these areas in the left hemisphere. The
      rostral site of elevated rCBF in the group was at the border of areas 24/24' and
      areas 32/32' although most cases had a site of elevation more rostral in the
      perigenual cingulate cortex. The ACC site of reduced rCBF was in areas 8 and 32
      and that in the PCC included much of areas 29/30 in the callosal sulcus, areas
      23b and 31 on the cingulate gyral surface and parietal area 7m. The localization
      of relative rCBF changes suggests different roles for the cingulate cortex in
      pain processing: (i) elevated rCBF in area 24' may be involved in response
      selection like nocifensive reflex inhibition; (ii) activation of the perigenual
      cortex may participate in affective responses to noxious stimuli like suffering
      associated with pain; and (iii) reduced rCBF in areas 8 and 32 may enhance pain
      perception in the perigenual cortex, while that in the PCC may disengage visually
      guided processes.

PMID- 8758954
TI  - Simultaneous recording of spontaneous activities and nociceptive responses from
      neurons in the pars compacta of substantia nigra and in the lateral habenula.
AB  - Using simultaneous extracellular single-unit recording in the pars compacta of
      the substantia nigra and in the lateral habenula of rats, 45 pairs of neurons
      responding to peripheral nociceptive stimulation were recorded. In 41 of these
      pairs, nigral dopaminergic neurons were inhibited by peripheral nociceptive
      stimulation, while lateral habenula neurons were excited. Moreover, in 14 pairs,
      when sweeps were triggered randomly by spontaneous spikes from lateral habenula
      neurons the spontaneous firing rate of the dopaminergic neurons during the first
      250 ms after the sweep was much lower than rates after this time period. In this
      case, the sweep was often triggered by burst-firing of lateral habenula neurons.
      Our results indicate a cross-correlation between the spontaneous activities of
      these two nuclei, suggesting that the excitation of lateral habenula neurons
      induced by peripheral nociceptive stimulation might be directly responsible for
      inhibition of nigral dopaminergic neurons.

PMID- 8758955
TI  - Dissociations in hippocampal 5-hydroxytryptamine release in the rat following
      Pavlovian aversive conditioning to discrete and contextual stimuli.
AB  - The experiments examined the release of 5-hydroxytryptamine using in vivo
      microdialysis methods in the hippocampus of freely moving rats following
      Pavlovian aversive conditioning to discrete and contextual stimuli. Differential
      conditioning was achieved by manipulating the interval between the offset of a
      discrete auditory 'clicker' stimulus and the onset of a mild foot-shock
      reinforcer (0.5 mA, 0.5 s). Foot-shock occurred either simultaneously with the
      last second of the discrete auditory stimulus (in short-trace subjects) or 60 s
      later (long-trace subjects). In this way, subjects were preferentially
      conditioned to the discrete stimulus and background 'contextual' stimuli
      respectively. During conditioning subjects also received two identical unpaired
      visual stimuli. At test, dialysates were collected and behavioural measures taken
      as all animals experienced (i) the aversive and two other 'neutral' environments,
      and (ii) the discrete unconditioned and conditioned stimuli presented in both
      aversive and neutral environments. Exposure to the aversive environment, but not
      to either of the two neutral environments, was associated with significantly
      increased hippocampal 5-hydroxytryptamine release in long-trace subjects. There
      was also a small but non-significant increase in 5-hydroxytryptamine release in
      short-trace animals. In contrast, hippocampal 5-hydroxytryptamine release was
      unaffected by presentation of either of the discrete stimuli under all
      conditions. The last result was obtained despite robust behavioural responses
      (freezing) to the discrete conditioned stimulus. These data do not agree with the
      hypothesis that aversive cues generally activate 5-hydroxytryptamine function in
      the hippocampus. Rather, they suggest a degree of specificity whereby 5
      hydroxytryptamine release in the hippocampus was determined primarily by other
      qualitative properties of the conditioned aversive stimulus, namely whether the
      aversive cue was discrete or contextual, as well as by the magnitude of
      conditioning.

PMID- 8758956
TI  - Perisynaptic location of metabotropic glutamate receptors mGluR1 and mGluR5 on
      dendrites and dendritic spines in the rat hippocampus.
AB  - Ionotropic and metabotropic (mGluR1a) glutamate receptors were reported to be
      segregated from each other within the postsynaptic membrane at individual
      synapses. In order to establish whether this pattern of distribution applies to
      the hippocampal principal cells and to other postsynaptic metabotropic glutamate
      receptors, the mGluR1a/b/c and mGluR4 subtypes were localized by
      immunocytochemistry. Principal cells in all hippocampal fields were reactive for
      mGluR5, the strata oriens and radiatum of the CA1 area being most strongly
      immunolabelled. Labelling for mGluR1b/c was strongest on some pyramids in the CA3
      area, weaker on granule cells and absent on CA1 pyramids. Subpopulations of non
      principal cells showed strong mGluR1 or mGluR5 immunoreactivity. Electron
      microscopic pre-embedding immunoperoxidase and both pre- and postembedding
      immunogold methods consistently revealed the extrasynaptic location of both
      mGluRs in the somatic and dendritic membrane of pyramidal and granule cells. The
      density of immunolabelling was highest on dendritic spines. At synapses,
      immunoparticles for both mGluR1 and mGluR5 were found always outside the
      postsynaptic membrane specializations. Receptors were particularly concentrated
      in a perisynaptic annulus around type 1 synaptic junctions, including the
      invaginations at 'perforated' synapses. Measurements of immunolabelling on
      dendritic spines showed decreasing levels of receptor as a function of distance
      from the edge of the synaptic specialization. We propose that glutamergic
      synapses with an irregular edge develop in order to increase the circumference of
      synaptic junctions leading to an increase in the metabotropic to ionotropic
      glutamate receptor ratio at glutamate release sites. The perisynaptic position of
      postsynaptic metabotropic glutamate receptors appears to be a general feature of
      glutamatergic synaptic organization and may apply to other G-protein-coupled
      receptors.

PMID- 8758957
TI  - Acidic calponin cloned from neural cells is differentially expressed during rat
      brain development.
AB  - Calponin is an actin-, tropomyosin- and Ca2+ calmodulin-binding protein that
      inhibits in vitro the actomyosin MgATPase. Basic and acidic variants of calponin
      have been described to date. Although the cerebral expression of calponin
      remained controversial for some time, transcripts encoding acidic calponin in the
      adult rat brain and in cultured cerebellar cells have been reported. In the
      present work, we report the expression of acidic calponin mRNAs and the isolation
      of cDNAs encoding the full-length acidic calponin in cultured neuronal and glial
      cells and in adult rat brain. Sequence analysis reveals that acidic calponin in
      the brain is identical to that previously described in rat aortic vascular smooth
      muscle. In situ hybridization shows that calponin is highly expressed during
      ontogenesis in granule cells of the dentate gyrus of the hippocampus, in all
      layers of the olfactory bulb and in cerebellar granule neurons of the external
      and internal layers. In the adult rat brain, calponin expression decreased in
      these fields, but increased in choroid plexus cells. Bergmann glial cells were
      also labelled by a calponin probe. The reverse transcription-coupled polymerase
      chain reaction confirms that calponin mRNA levels are highest in the early stages
      of hippocampal development and that expression levels are low in adult
      hippocampi. The developmental expression pattern of brain acidic calponin
      suggests that calponin could be involved in contractile activity associated with
      neural cell proliferation or neuronal migration.

PMID- 8758958
TI  - Non-synaptic release of ATP by electrical stimulation in slices of rat
      hippocampus, cerebellum and habenula.
AB  - ATP is thought to be a fast neurotransmitter in the medial habenula region of the
      brain, and may be coreleased with other transmitters, for example with glutamate
      in the hippocampus. We monitored ATP release in rat brain slices using the
      bioluminescent indicator system luciferin-luciferase. Electrical stimulation of
      the hippocampus, cerebellum or habenula led to ATP release, but this release was
      calcium-independent and was not blocked by tetrodotoxin, or by other agents found
      to block ATP release from red blood cells. Although calcium-dependent ATP release
      may occur in response to electrical stimulation, it appears to be overwhelmed by
      calcium-independent release, which may result from electroporation of cells close
      to the stimulating electrode. Consistent with this, uptake into cells of the
      fluorescent dye Lucifer yellow was promoted by electrical stimulation. Our data
      undermine a previous suggestion, based on use of the luciferin-luciferase
      technique, that ATP is synaptically released with glutamate in the hippocampus.

PMID- 8758959
TI  - Activation of multiple metabotropic glutamate receptor subtypes prevents NMDA
      induced excitotoxicity in rat hippocampal slices.
AB  - Metabotropic glutamate receptors (mGluRs) belong to a relative large receptor
      family consisting of multiple members with important roles in a number of brain
      functions. We report here that activation of mGluRs prevents the neurotoxic
      effect induced by N-methyl-D-aspartate (NMDA) in slices from the rat hippocampus.
      Neuroprotection was elicited when slices were simultaneously exposed to both the
      selective mGluR agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid
      (tACPD) and NMDA. Persisting stimulation of mGluRs after the toxic exposure did
      not improve the survival of pyramidal or granular cells. The neuroprotection
      elicited by tACPD toxic exposure did not improve the survival of pyramidal or
      granular cells. The neuroprotection elicited by tACPD was also evoked by its
      active isomer, (1S, 3R)-ACPD, and was prevented by the selective mGluR antagonist
      (+)-alpha-methyl-4-carboxyphenyl-glycine (500 microM), confirming that mGluR
      activation is involved in the mechanism of action of tACPD. The effect of 100
      microM tACPD was reproduced by 100 microM quisqualate, an agonist of mGluR2 and
      mGluR3 subtypes. No neuroprotection was induced by L-2-amino-4-phosphonobutyrate,
      a selective agonist for mGluR4, mGluR6, mGluR7 and mGluR8, at 500 microM. Since
      the NMDA-mediated cell death in hippocampal slices is considered relevant to
      ischaemia-induced brain injury, these results indicate that mGluRs may be
      important safety devices used by neurons to decrease their sensitivity to
      excitotoxic stimuli and increase their chance of survival.

PMID- 8758960
TI  - Thalamic and basal forebrain afferents modulate the development of parvalbumin
      and calbindin D28k immunoreactivity in the barrel cortex of the rat.
AB  - In the adult barrel cortex of the rat the calcium-binding proteins calbindin D28k
      (CALB) and parvalbumin (PARV) are found in separate populations of GABAergic
      nonpyramidal neurons. In layers II to IV of the barrel cortex most PARV
      immunoreactive neurons are likely to derive from a subpopulation of CALB
      immunoreactive neurons whose CALB immunoreactivity ceases when they begin to
      express PARV between the second and third postnatal weeks. The aim of this study
      was to investigate the influence of subcortical afferents on the neurochemical
      differentiation of cortical PARV- and CALB-immunoreactive nonpyramidal neurons
      during development of the barrel cortex. We produced unilateral excitotoxic
      lesions with a single injection of ibotenic acid (0.5 microl, 0.05 M) in
      different subcortical nuclei in 7- to 8-day-old rats. Lesions involving the
      ventroposterior thalamic nuclei resulted in delayed development of PARV and CALB
      immunoreactivity in the barrel cortex. One week after ibotenic acid injections a
      transient decrease in the number of PARV-immunoreactive neurons in layer IV was
      observed, together with increased numbers of CALB-immunoreactive neurons in all
      cortical layers. The number of nonpyramidal neurons displaying coexistence of
      PARV and CALB in the lesioned hemisphere also increased compared with the numbers
      in the control hemisphere or control littermates. In contrast, lesions affecting
      the globus pallidus, zona incerta and reticular thalamic nucleus transiently
      increased the number of PARV-immunoreactive neurons in layers II and III, but had
      no effect on the number of CALB-positive cells. From 3 weeks onwards no
      differences were found between control and lesioned hemispheres after injections
      into either the ventroposterior thalamic nuclei or the magnocellular basal
      forebrain. These results suggest that CALB and PARV expression in nonpyramidal
      cortical neurons can be reversibly modulated in opposite directions by different
      cortical afferents during postnatal development.

PMID- 8758961
TI  - Selective immunolesioning of the basal forebrain cholinergic system disrupts
      short-term memory in rats.
AB  - Selective depletion of nerve growth factor receptor-bearing neurons in the basal
      forebrain cholinergic system nuclei by the immunotoxin 192 IgG-saporin offers a
      new and highly useful tool for the study of the role of the forebrain cholinergic
      system in cognitive functions. In the present study, we have tested the effects
      of 192 IpG-saporin in an operant delayed matching-to-position task which has
      previously been used to discriminate between delay-dependent learning impairments
      and delay-independent disturbances of non-mnemonic processes. Rats were first
      trained to criterion performance and then received intraventricular injections of
      5 microg of 192 IgG-saporin 4 weeks prior to a second testing session. Rats with
      192 IgG-saporin lesions displayed a significant delay-dependent decline in
      performance compared to normal controls, indicating a deficit in short-term
      memory. Administration of the muscarinic blocker scopolamine (0.5 mg/kg, i.p.)
      produced more pronounced impairment in the performance of the normal control rats
      across all delays, and induced further impairment also in animals with 192 IgG
      saporin lesions. These effects were not observed following control injections of
      methyl scopolamine, suggesting that the impairment induced by scopolamine was due
      to the blockade of central muscarinic receptors. No improvement in performance
      was observed in either group following systemic treatment with the muscarinic
      cholinergic agonist arecoline (1.00 mg/kg). Biochemical and morphological
      analyses confirmed the selective and severe (>90-95%) depletion of cholinergic
      neurons throughout the septal-diagonal band area and the nucleus basalis region
      by the intraventricular 192 IgG-saporin treatment. Although the immunotoxin was
      observed to produce additional damage to the cerebellar Purkinje cells, no gross
      motor abnormalities were observed that could contribute to the effects on
      accuracy in the task used here. In conclusion, the results show that selective
      combined lesions of the basal forebrain cholinergic neurons in the septal
      diagonal band area and nucleus basalis produce long-lasting impairments in short
      term memory, thus providing further support for a role of this system in
      cognitive functions.

PMID- 8758962
TI  - Dopamine D1 receptor-mediated facilitation of GABAergic neurotransmission in the
      rat strioentopenduncular pathway and its modulation by adenosine A1 receptor
      mediated mechanisms.
AB  - By using in vivo microdialysis it was found that one of the main functions of
      striatal dopamine D1 receptors is to selectively facilitate GABAergic
      neurotransmission in the 'direct' strioentopeduncular pathway. D1 receptors
      localized in the entopeduncular nucleus were also found to facilitate GABA
      release. However, results obtained from in vivo microdialysis, in vivo
      electrochemistry, immunohistochemistry and confocal laser microscopy suggested
      that entopeduncular D1 receptors could only be activated under pharmacological
      conditions. Adenosine A1 receptors were found to antagonistically modulate the D1
      mediated regulation of the strioentopeduncular pathway. Furthermore, using in
      situ hybridization D1 and A1 receptors were shown to be colocalized in medium
      sized striatal neurons. These results show that the strioentopeduncular neuron is
      a main locus for adenosine-dopamine interactions in the brain.

PMID- 8758964
TI  - Prognostic value of abnormal EEG transients in preterm and full-term neonates.
AB  - The prognostic value of abnormal EEG transients was investigated in 362 subjects
      submitted to EEG recording during the neonatal age and followed-up at least until
      the 12th month of corrected age. The incidence of negative and positive spikes
      and sharp waves, of rhythmic sharp theta and delta activities and of alpha
      discharges were evaluated by means of a quantitative score. These abnormal EEG
      transients appeared to be generally rare and even absent in a large number of
      subjects. In infants with normal outcome their incidence tends to increase from
      low postmenstrual ages towards term period. Full-term newborns with abnormal
      neurological outcome presented a significantly higher incidence of these
      transients. Preterm infants with unfavourable evolution showed a higher incidence
      only when submitted to EEG recording at around term age. However, no difference
      between subjects with normal and abnormal outcome was detected in preterm infants
      when evaluated at low postmenstrual ages. The hypothesis that at low
      postmenstrual ages brain damage might, on the one hand, give rise to abnormal
      transients and, on the other, alter the "capability' of manifesting them
      (together with other EEG maturational aspects), might explain these results.

PMID- 8758963
TI  - Brain-derived neurotrophic factor reversed experience-dependent synaptic
      modifications in kitten visual cortex.
AB  - During a critical period of early postnatal development the functional
      architecture of the visual cortex is shaped by experience-dependent circuit
      selection following a Hebbian mechanism. One consequence is that monocular
      deprivation (MD) leads to competitive repression of the input from the deprived
      eye. Recently it has been proposed that this process might involve activity
      dependent competition for neurotrophic substances because the synthesis of brain
      derived neurotrophic factor (BDNF) is regulated by visual input. Here we
      investigate the effects of intracortical infusion of BDNF and nerve growth factor
      (NGF) on MD effects in the visual cortex. Neuronal responses were monitored with
      optical and single unit recording techniques in the visual cortex of kittens that
      had been infused intracortically either with BDNF, NGF or cytochrome C while
      subjected to MD for 1 week during the peak of the critical period. NGF or
      cytochrome C had no effect on the consequences of MD. After BDNF treatment, by
      contrast, ocular dominance (OD) shifted towards the deprived eye in a zone
      extending 2.5-3.5 mm from the infusion cannula, and neurons lost their
      orientation selectivity. At intermediate distances both eyes activated the cortex
      equally well and responses were again tuned for orientation; at still larger
      distances OD was shifted towards the normal eye. Thus, BDNF antagonizes the
      functional effects of MD and at high concentrations causes paradoxical
      disconnection of non-deprived afferents and a loss of orientation selectivity.

PMID- 8758965
TI  - Nocturnal sleep latencies among alert, alert-deprived and sleepy subjects.
AB  - Twenty-seven healthy, asymptomatic subjects participated in a study to determine
      repeated nocturnal sleep latencies as a function of level of daytime sleepiness.
      Subjects were screened polysomnographically and were determined to be free of any
      sleep pathology. Nine subjects had a screening multiple sleep latency test (MSLT)
      of < or = 5 min and 18 had a MSLT of > or = 10 min. Subjects were assigned to 3
      groups, sleepy (MSLT < or = 5 min), alert, and alert sleep-deprived groups (MSLT
      > or = 10 min). Repeated nocturnal latencies to sleep were determined at 2300,
      0110, 0310 and 0510 h on 2 nights with at least 5 days between nights. The
      results showed a main effect of group on the repeated nocturnal sleep latencies.
      Post-hoc tests demonstrated longer repeated nocturnal latencies among alert
      subjects compared to the sleepy and alert sleep-deprived subjects. The latter two
      groups had comparable sleep latencies. A significant main effect of time of night
      was also shown. The 0510 h latency was significantly shorter than the latencies
      at 2300 and 0110 h. The 0310 h latency was significantly shorter than the 0110 h
      latency and comparable to the 2300 and 0510 h latency. Significant correlations
      were found between daytime MSLT, repeated nocturnal sleep latencies, and
      nocturnal sleep time. These results show systematic differences in repeated
      nocturnal sleep latencies among sleep and alert subjects and extend the already
      described characteristics of these subjects by comparing them to a group of alert
      sleep-deprived subjects.

PMID- 8758966
TI  - A technique for sequential measurements of DC neuromagnetic fields.
AB  - Magnetoencephalography (MEG) has the capability of detecting DC neuromagnetic
      fields which might arise from migraine, stroke, head trauma, etc. However, such
      fields are not readily measured in serial fashion for technical reasons,
      including arbitrary neuromagnetometer baselines, residual DC fields which vary
      from place to place inside conventional magnetically shielded rooms, and
      especially the high sensitivity of such measurements to small changes in distance
      between the probe and head. A technique is described to carry out such
      measurements by raising and lowering the subject under the probe and calibrating
      the DC shift against the amplitude of spontaneous activity.

PMID- 8758967
TI  - N2, P3 and the lateralized readiness potential in a nogo task involving selective
      response priming.
AB  - Motor inhibition and its correlates in the event-related potential (ERP) are
      often studied in go/nogo tasks. However, go and nogo trials differ in their motor
      and their attentional requirements, rendering an interpretation of corresponding
      changes in ERP components difficult. As an alternative strategy to study motor
      inhibition, a hybrid choice-reaction go/nogo procedure involving selective
      response priming was used. Eighteen subjects performed the task. Response time
      (RT) and error measures as well as the lateralized readiness potential (LRP)
      indicated that responses were primed by flanker stimuli that were associated with
      one of the two possible responses. In nogo trials, selective response priming
      influenced the N2 amplitude whereas the P3 amplitude was unaffected. Because the
      N2 appeared irrespective of whether an erroneous response was correctable (in go
      trials) or not (in nogo trials), we conclude that the N2 reflects either the
      detection or the inhibition of an inappropriate tendency to respond.

PMID- 8758968
TI  - Brain potentials before and during memory scanning.
AB  - Brain potentials were recorded from 10 normal subjects engaged in a 3-item
      auditory verbal short-term memory task. A fixed interval (3 s) between the last
      memory item and the probe was compared to a random interval (1.8-4.2 s with a
      mean of 3 s). Subjects indicated by button press whether the probe was or was not
      a member of the memory-set. The same 3-item task was also presented as a counting
      task and required a button press to the "fourth stimulus' (the probe). The
      amplitudes of several slow potential shifts preceding and following the probe,
      and the amplitudes and latencies of the accompanying short duration components
      (N100, P200) were measured. When the probe appeared at a fixed interval, the
      amplitude of a slow negative potential in the 300 ms period preceding the probe
      was slightly larger in the memory than in the counting task. When the probe
      appeared at a random interval in the memory task, the slow negative shift
      preceding the probe was absent. Another slow negative shift that peaked at
      approximately 376 ms after the probe was present in the memory tasks but was
      absent in the counting task. The amplitude of a late positive shift that peaked
      at approximately 700 ms after the probe was not different within the memory
      tasks, or between the memory and counting tasks. N100 amplitude but not P200
      amplitude was larger in the memory task when the probe occurred at a fixed than
      at a random interval. These results suggest that the amplitude of a slow negative
      shift preceding the probe was related primarily to a temporal expectancy for the
      appearance of the probe and to a lesser extent to memory processes. In contrast,
      a slow negative shift that followed the probe occurred only during the memory
      tasks.

PMID- 8758969
TI  - Frontal processing negativity in a visual selective attention task.
AB  - The auditory processing negativity has been associated with the maintenance of an
      internal representation of context and has been shown to be dependent on the
      integrity of the prefrontal cortex. Previous visual selective attention studies
      have failed to show consistent evidence of a frontal processing negativity. The
      present study employed a multi-dimensional visual selective attention task,
      modelled after Hillyard and Munte (Percept. Psychophys., 1984, 36: 185-198).
      Subjects responded to infrequent target stimuli of a particular location, color
      and height combination, while ignoring all stimuli differing from the target on
      any of these dimensions. Consistent with previous literature, at posterior sites,
      location selection resulted in enhancement of P1 and N1 amplitude, followed by
      color selection within the attended location at around 200 ms. These effects were
      most pronounced contralaterally. However, unlike previous studies, a large
      prolonged processing negativity was evident at all frontal sites. This effect
      involved three components, an early frontally negative component peaking around
      the N1, a frontocentral negativity maximal at 300 ms and a long-lasting
      widespread negativity beginning after 500 ms. Processing of location preceded the
      onset of color and location/color conjunction processing, suggesting hierarchical
      stimulus feature analysis. However, at posterior temporal sites there was
      evidence of parallel color processing in the unattended location.

PMID- 8758970
TI  - Sound-evoked electrocortical desynchronization is inhibited by N omega-nitro-L
      arginine methyl ester microinfused into the inferior colliculi in rats.
AB  - In previous experiments we have shown that systemic or intracerebroventricular
      administration of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of
      nitric oxide (NO) synthase, is able to significantly reduce sound-evoked
      electrocortical (ECoG) desynchronization in rats. The present experiments were
      aimed at identifying the site(s) of the brain through which these effects are
      mediated. L-NAME (200 and 300 nmol), oxyhaemoglobin (200 and 300 nmol), a NO
      trapping agent, and methylene blue (100 and 150 nmol), an inhibitor of guanylate
      cyclase and NO synthase, given bilaterally into the inferior colliculi, but not
      in other relay stations of the acoustic pathway, prevented the reduction in ECoG
      amplitude induced by sound stimulation in rats. Significant reduction of sound
      evoked ECoG desynchronization has also been observed in rats receiving injection
      of CGP37849 (125 and 500 pmol) and LY274614 (125 pmol), two competitive N-methyl
      D-aspartate receptor antagonists into the inferior colliculi. The present results
      show that the inferior colliculus represents the main site where sound-evoked
      ECoG desynchronization is prevented by L-NAME and provide further support for the
      hypothesis that NO may play a role at this level in the control of the measured
      response.

PMID- 8758971
TI  - Age increases brain complexity.
AB  - This study investigated age-related changes in the human brain function using
      both traditional EEG analysis (power spectra) and the correlational dimension, a
      measure reflecting the complexity of EEG dynamics and, probably, the complexity
      of neurophysiological processes generating the EEG. Assuming that the
      accumulation of individual experience is determined by the formation of
      functionally related groups of neurons showing a repetitive synchronous
      activation (cell assemblies), an increase in the number of such independently
      oscillating cortical cell assemblies can be expected, despite a decline of some
      metabolic and memory functions with normal ageing. Thus, the "wisdom of old age'
      may find its neurophysiological basis in greater complexity of brain dynamics
      compared to young ages. The experimental hypothesis was that EEG dimension
      steadily increases with age. In order to test this hypothesis the resting EEGs of
      5 age groups from 7 to 60 were analysed. The results confirm the hypothesis:
      after a jump in the brain dynamics complexity during puberty a linear increase
      with age is observed. During maturation (7-25 years), the maximum gain in
      complexity occurs over the frontal associative cortex.

PMID- 8758972
TI  - Simultaneous intracranial and extracranial recording of interictal epileptiform
      activity in patients with drug resistant partial epilepsy: patterns of conduction
      and results from dipole reconstructions.
AB  - Ten patients with complex partial epileptic seizures undergoing invasive
      video/EEG-monitoring were recorded with a combination of 10 subdural strip
      electrode contacts (subtemporal + lateral temporal), and 22 extracranial
      recording sites. In each patient several spikes with different intracranial
      distributions were identified, and spikes with similar distributions were
      averaged together with their extracranial activity. Dipole analysis of the
      extracranial activity was performed with the BESA program (Scherg, Garching
      Instrumente, Munchen). In the horizontal plane subtemporal spikes gave oblique
      posterior, and lateral temporal spikes straight lateral or oblique anterior
      dipole orientations. In the coronal plane all spikes had an elevated orientation,
      most pronounced for medial subtemporal spikes. Dipole locations did not separate
      as well as dipole orientations. In our opinion our results would be difficult to
      explain without postulating a substantial degree of volume conduction from deep
      temporal areas to the surface. We conclude that dipole analysis of the interictal
      epileptiform activity does provide substantial information about which parts of
      the temporal lobe are involved in the epileptogenic process, making the method a
      useful tool in the preoperative investigation of patients with drug resistant
      partial epilepsy.

PMID- 8758973
TI  - Improved dipole localization using local mesh refinement of realistic head
      geometries: an EEG simulation study.
AB  - A systematic evaluation of dipole localization accuracy using the boundary
      element method is presented. EEG simulations are carried out with dipoles located
      in the right parietal and temporal regions of the head. Uniformly meshed and
      locally refined head models are considered in both spherical and realistic
      geometries. An initial study determines the influence upon the localization
      accuracy of the dipole depth below the brain surface, of its orientation (radial
      and tangential), and of the global and local mesh densities. Simulated potential
      data are computed analytically in the spherical case, and numerically using a
      very fine (locally refined) model in the realistic case. Results in both
      geometries show that in order to get localization errors of about 2-4 mm,
      uniformly meshed models may be used for dipoles located at depths greater than 20
      mm, whereas locally refined models should be used for shallower dipoles. Two
      other studies show how the localization accuracy depends upon the size of the
      local refinement area and upon the number of electrodes (19, 32, 63). Results
      show that a large number of electrodes brings significant improvements,
      especially for shallow and tangential dipoles.

PMID- 8758974
TI  - Scalp-recorded direct current potential shifts induced by hypocapnia and
      hypercapnia in humans.
AB  - Shifts in scalp-recorded direct current (DC) potential were studied in relation
      to the changes in end-tidal partial CO2 (PACO2) or O2 (PAO2) of the expired gas
      either during hyperventilation (HV), hypoventilation (HYPO) or inhalation of high
      CO2 content air during HV or HYPO in 10 healthy subjects. The DC potential was
      obtained through a chopper stabilized type of DC amplifier from Cz referred to
      linked earlobes. Each session was comprised of 3 min control, 3 min experimental
      and 5 min recovery periods. HV induced a negative shift of the DC potential of
      765.5 +/- 203.0 microV (mean +/- SEM). Inhalation of 6% CO2 air during HYPO
      induced a positive shift of the DC potential of 280.6 +/- 62.8 microV (mean +/-
      SEM). The magnitude of the DC potential shifts was linearly dependent on the
      changes in the end-tidal PACO2 (r = 0.78, P < 0.0001). There was no change in the
      cephalic inter-electrodes impedance during each experimental session. The results
      suggest that the scalp-recorded DC potentials reflect the changes in cortical
      excitability associated with the PACO2 level.

PMID- 8758975
TI  - Molecular genetic studies confirm the role of brassinosteroids in plant growth
      and development.

PMID- 8758976
TI  - A plant kinesin heavy chain-like protein is a calmodulin-binding protein.
AB  - Calmodulin, a calcium modulated protein, regulates the activity of several
      proteins that control cellular functions. A cDNA encoding a unique calmodulin
      binding protein, PKCBP, was isolated from a potato expression library using
      protein-protein interaction based screening. The cDNA encoded protein bound to
      biotinylated calmodulin and 35S-labeled calmodulin in the presence of calcium and
      failed to bind in the presence of EGTA, a calcium chelator. The deduced amino
      acid sequence of the PKCBP has a domain of about 340 amino acids in the C
      terminus that showed significant sequence similarity with the kinesin heavy chain
      motor domain and contained conserved ATP- and microtubule-binding sites present
      in the motor domain of all known kinesin heavy chains. Outside the motor domain,
      the PKCBP showed no sequence similarity with any of the known kinesins, but
      contained a globular domain in the N-terminus and a putative coiled-coil region
      in the middle. The calmodulin-binding region was mapped to a stretch of 64 amino
      acid residues in the C-terminus region of the protein. The gene is differentially
      expressed with the highest expression in apical buds. A homolog of PKCBP from
      Arabidopsis (AKCBP) showed identical structural organization indicating that
      kinesin heavy chains that bind to calmodulin are likely to exist in other plants.
      This paper presents evidence that the motor domain has microtubule stimulated
      ATPase activity and binds to microtubules in a nucleotide-dependent manner. The
      kinesin heavy chain-like calmodulin-binding protein is a new member of the
      kinesin superfamily as none of the known kinesin heavy chains contain a
      calmodulin-binding domain. The presence of a calmodulin-binding motif and a motor
      domain in a single polypeptide suggests regulation of kinesin heavy chain driven
      motor function(s) by calcium and calmodulin.

PMID- 8758977
TI  - Expression of the early nodulin, ENOD40, in soybean roots in response to various
      lipo-chitin signal molecules.
AB  - The lipo-chitin (LCO) nodulation signal (nod signal) purified from Bradyrhizobium
      japonicum induced nodule primordia on soybean (i.e. Glycine soja) roots. These
      primordia were characterized by a bifurcated vascular connection, cortical cell
      division, and the accumulation of mRNA of the early nodulin gene, ENOD40. A
      chemically synthesized LCO identical in structure to the Nod signal purified from
      B. japonicum cultures showed the same activity when inoculated on to soybean
      roots. Surprisingly, synthetic LCO or chitin pentamer, inactive in inducing root
      hair curling (HAD) or cortical cell division (NOI) in G. soja, induced the
      transient accumulation of ENOD40 mRNA. In roots inoculated with such LCO, ENOD40
      mRNA was abundant at 40 h after inoculation but decreased to the background
      levels 6 days after inoculation. In contrast, nod signals active in inducing HAD
      and NOI induced high levels of ENOD40 accumulation at 40 h and 6 days after
      inoculation. In situ hybridization analysis showed that ENOD40 mRNA accumulated
      in the pericycle of the vascular bundle at 24 h after root inoculation with nod
      signal. At 6 days post-inoculation with nod signal, ENOD40 expression was seen in
      dividing subepidermal cortical cells. These results provide morphological and
      molecular evidence that nodule induction in soybean in response to purified or
      synthetic nod signal is similar, if not identical, to nodule formation induced by
      bacterial inoculation. Surprisingly, ENOD40 mRNA accumulation occurs in response
      to non-specific chitin signals. This suggests that, in the case of ENOD40,
      nodulation specificity is not determined at the level of initial gene expression.

PMID- 8758979
TI  - Benzothiadiazole induces disease resistance in Arabidopsis by activation of the
      systemic acquired resistance signal transduction pathway.
AB  - Benzothiadiazole (BTH) is a novel chemical activator of disease resistance in
      tobacco, wheat and other important agricultural plants. In this report, it is
      shown that BTH works by activating SAR in Arabidopsis thaliana. BTH-treated
      plants were resistant to infection by turnip crinkle virus, Pseudomonas syringae
      pv 'tomato' DC3000 and Peronospora parasitica. Chemical treatment induced
      accumulation of mRNAs from the SAR-associated genes, PR-1, PR-2 and PR-5. BTH
      treatment induced both PR-1 mRNA accumulation and resistance against P.
      parasitica in the ethylene response mutants, etr1 and ein2, and in the methyl
      jasmonate-insensitive mutant, jar1, suggesting that BTH action is independent of
      these plant hormones. BTH treatment also induced both PR-1 mRNA accumulation and
      P. parasitica resistance in transgenic Arabidopsis plants expressing the nahG
      gene, suggesting that BTH action does not require salicylic acid accumulation.
      However, because BTH-treatment failed to induce either PR-1 mRNA accumulation or
      P. parasitica resistance in the non-inducible immunity mutant, nim1, it appears
      that BTH activates the SAR signal transduction pathway.

PMID- 8758980
TI  - Expression of Escherichia coli branching enzyme in tubers of amylose-free
      transgenic potato leads to an increased branching degree of the amylopectin.
AB  - In order to increase the branching degree of potato tuber starch, the gene
      encoding branching enzyme (glgB) of Escherichia coli was expressed in the amylose
      free potato mutant. The E. coli glgB was cloned in the binary vector pBIN19 under
      the transcriptional control of the potato Granule Bound Starch Synthase (GBSS)
      promoter and transitpeptide sequence. The E. coli glgB was cloned behind the two
      N-terminal amino acids of the GBSS mature protein, creating a chimeric protein.
      Transgenic plants were obtained which expressed the E. coli branching enzyme as
      was shown by the presence of mRNA and protein in the tubers. Correctly processed
      protein was found both in the soluble and starch granule bound protein fraction.
      Analysis of the starch showed an increase in the branching degree (DE) of up to
      25% more branchpoints. The increase in the number of branchpoints was due to the
      presence of more short chains, with a degree of polymerization (DP) of 16 glucose
      residues or less in the amylopectin. Changes in other characteristics of the
      starch, such as average chain length (CL) and lambda max, indicated a more
      branched structure for starch of transformed plants as well.

PMID- 8758981
TI  - Strong, constitutive expression of the Arabidopsis ACT2/ACT8 actin subclass in
      vegetative tissues.
AB  - Arabidopsis has a complex and ancient actin gene family encoding six divergent
      subclasses of proteins. One subclass is represented by ACT2 and ACT8, which
      encode nearly identical proteins. These two genes differ significantly in
      flanking and intron sequences and in silent nucleotide positions within codons.
      Gene-specific RNA gel blot hybridization and reverse transcriptase-mediated
      polymerase chain reaction (RT-PCR) assays showed that ACT2 and/or ACT8mRNAs were
      coordinately and strongly expressed in leaves, roots, stems, flowers, pollen, and
      siliques. Together they account for greater than 80% of the actin mRNA in most
      Arabidopsis organs. The 5' flanking regions, including the promoter, the mRNA
      leader exon, an intron in the mRNA leader, and the first 19 codons, were coupled
      to a beta-glucuronidase (GUS) reporter gene and transformed into Arabidopsis. The
      ACT2/GUS construct was expressed strongly in nearly all the vegetative tissues in
      seedlings, juvenile plants, and mature plants. These activities persisted in
      older tissues. Little or no expression was observed in seed coats, hypocotyls,
      gynoecia, or pollen sacs. In contrast, the expression of the ACT8/GUS construct
      was weaker. It was observed only in a subset of the organs and tissues expressing
      ACT2/GUS and was not significantly expressed in the flower. ACT2, ACT8, and
      ACT8/GUS mRNAs were present at moderate to high levels in pollen, and yet neither
      ACT2/GUS nor ACT8/GUS enzyme expression could be detected in pollen. This
      suggested a mechanism of translational control affecting ACT2 and ACT8 expression
      in some tissues. The conservation of protein sequence and overlapping patterns of
      expression, in spite of significant DNA sequence divergence, suggests that the
      function and regulation of these two genes have been conserved during the
      evolution of the Brassicaceae.

PMID- 8758982
TI  - Transcript processing internal to a mitochondrial open reading frame is
      correlated with fertility restoration in male-sterile sorghum.
AB  - A chimeric mitochondrial DNA (mtDNA) configuration of the cytoplasmic male
      sterile (cms) sorghum line IS1112C includes a 321 bp open reading frame
      designated orf107, encoding a predicted polypeptide product of 11.85 kDa. The
      open reading frame, similar to several other genes associated with cms, consists
      of amino-terminal sequences derived from an obligate gene. Unlike other examples
      to date, however, the carboxy-terminal sequences are highly similar to the
      carboxy terminus of an open reading frame implicated in cms of rice, orf79. The
      amino-terminal 31 residues of orf107 are 84% similar to atp9, and the carboxy
      terminal 49 residues are 57% identical and 80% similar to the carboxy terminus of
      orf79. Transcripts of orf107 are edited, with four C-to-U changes that alter
      amino acids. Sorghum lines partially or fully restored to fertility exhibit a
      high-efficiency internal-orf107 transcript processing activity, precluding
      abundant whole-length transcripts, while male-sterile lines exhibit only a trace
      of the activity. Previous data on the abundance of a 12kDa in organello
      synthesized polypeptide in male-sterile versus male-fertile lines are correlated
      with differential orf107 transcript processing activity of these lines.
      Examinations of backcross and F2 lines suggest a gametophytic mode of
      restoration, and indicate that enhanced transcript processing activity is
      necessary, but not sufficient, to restore full fertility. These novel
      observations indicate that mitochondrial open reading frames associated with cms
      in different species can include highly similar motifs, and that fertility
      restoration could involve a mechanism by which synthesis of a cms-associated gene
      product may be precluded through internal transcript cleavage.

PMID- 8758983
TI  - The developmentally regulated bZIP factor ROM1 modulates transcription from
      lectin and storage protein genes in bean embryos.
AB  - Expression of the MAT genes DLEC2 and PHS beta, coding for phytohemagglutinin L
      subunit and beta-phaseolin, respectively, is coordinately induced in bean embryos
      at the onset of seed maturation and regulated at the level of transcription.
      Previously, it was reported that expression of DLEC2 and PHS beta genes is
      positively regulated by the acidic transcription activator PvALF. This article
      describes the regulator of MAT1 (ROM1), a basic/leucine-zipper protein that binds
      to hybrid G box/C box motifs found on the DLEC2 and PHS beta seed enhancers. ROM1
      repressed DLEC2- and PHS beta-driven expression and antagonized transactivation
      of either promoter by PvALF, in a dosage-dependent manner. By contrast, a
      PvALF/ROM1 hybrid protein activated transcription. Both repression by ROM1 and
      activation by the hybrid protein required the presence of intact G-box/C-box
      motifs. The abundance of ROM1 mRNA in embryos was highest during the cotyledon
      stage and decreased rapidly at the beginning of maturation, as phytohemagglutinin
      and phaseolin mRNAs were induced. The results demonstrate that ROM1 is a DNA
      binding site-dependent repressor and point to its possible role as a negative
      modulator of PvALF-activated transcription of MAT genes.

PMID- 8758986
TI  - Vectors carrying two separate T-DNAs for co-transformation of higher plants
      mediated by Agrobacterium tumefaciens and segregation of transformants free from
      selection markers.
AB  - Novel 'super-binary' vectors that carried two separate T-DNAs were constructed.
      One T-DNA contained a drug-resistance, selection-marker gene and the other
      contained a gene for beta-glucuronidase (GUS). A large number of tobacco
      (Nicotiana tabacum L.) and rice (Oryza sativa L.) transformants were produced by
      Agrobacterium tumefaciens LBA4404 that carried the vectors. Frequency of co
      transformation with the two T-DNAs was greater than 47% GUS-positive, drug
      sensitive progeny were obtained from more than half of the co-transformants.
      Molecular analyses by Southern hybridization and polymerase chain reactions
      confirmed integration and segregation of the T-DNAs. Thus, the non-selectable T
      DNA that was genetically separable from the selection marker was integrated into
      more than a quarter of the initial, drug-resistant transformants. Since various
      DNA fragments may be inserted into the non-selectable T-DNA by a simple
      procedure, these vectors will likely be very useful for the production of marker
      free transformants of diverse plant species. Delivery of two T-DNAs to plants
      from mixtures of A. tumefaciens was also tested, but frequency of co
      transformation was relatively low.

PMID- 8758987
TI  - Hypermutagenic PCR involving all four transitions and a sizeable proportion of
      transversions.
AB  - Very complex mutant libraries of the dihydrofolate reductase (DHFR) gene encoded
      by the Escherichia coli plasmid R67 were created using hypermutagenic PCR with
      biased deoxynucleotide triphosphate (dNTP) concentrations. Exploiting the
      particular stability of the G:T mismatch, the DHFR gene could be enriched in A+T
      by employing biased deoxypyrimidine triphosphate concentrations, i.e. [dTTP] >
      [dCTP]. A sizeable fraction of hypermutants were functional. A combination of
      [dTTP] > [dCTP] and [dGTP] > [dATP] biases generated mutations at unexpectedly
      low frequencies. This could be overcome by the addition of Mn2+ cations. Overall
      mutation frequencies of 10% per amplification (range 4-18% per clone) could be
      attained. All four transitions and a smaller number of transversions were
      produced throughout the gene. PCR mutagenesis could be so extensive as to
      inactivate all amplified versions of the gene.

PMID- 8758989
TI  - DNA bending by the silencer protein NeP1 is modulated by TR and RXR.
AB  - NeP1 binds to the F1 silencer element of the chicken lysozyme gene and, in the
      presence of TR, v-ERBA or RAR, synergistically represses transcriptional
      activity. This repression involves a silencing mechanism acting independently of
      the relative promoter position. Here we show that NeP1 alone can induce a
      significant directed bend on DNA. The chicken homologue of human NeP1, CTCF,
      shows identical binding and bending properties. In contrast, the isolated DNA
      binding domain of CTCF efficiently binds DNA, but fails to confer bending.
      Similarly, the TR-RXR hetero- or homodimer, binding adjacent to NeP1 at the F2
      sequence, do not show significant DNA bending. The binding of the T3 ligand to TR
      changes neither the magnitude nor the direction of the NeP1 induced bend.
      However, when all factors are bound simultaneously as a quaternary complex, the
      TR-RXR heterodimer changes the location of the bend center, the flexure angle and
      the bending direction.

PMID- 8758988
TI  - Analysis of the mechanism of the Serratia nuclease using site-directed
      mutagenesis.
AB  - Based on crystal structure analysis of the Serratia nuclease and a sequence
      alignment of six related nucleases, conserved amino acid residues that are
      located in proximity to the previously identified catalytic site residue His89
      were selected for a mutagenesis study. Five out of 12 amino acid residues
      analyzed turned out to be of particular importance for the catalytic activity of
      the enzyme: Arg57, Arg87, His89, Asn119 and Glu127. Their replacement by alanine,
      for example, resulted in mutant proteins of very low activity, < 1% of the
      activity of the wild-type enzyme. Steady-state kinetic analysis of the mutant
      proteins demonstrates that some of these mutants are predominantly affected in
      their kcat, others in their Km. These results and the determination of the pH and
      metal ion dependence of selected mutant proteins were used for a tentative
      assignment for the function of these amino acid residues in the mechanism of
      phosphodiester bond cleavage by the Serratia nuclease.

PMID- 8758990
TI  - Asn-tRNA in Lactobacillus bulgaricus is formed by asparaginylation of tRNA and
      not by transamidation of Asp-tRNA.
AB  - In many organisms (e.g., gram-positive eubacteria) Gin-tRNA is not formed by
      direct glutaminylation of tRNAGln but by a specific transamidation of Glu
      tRNAGln. We wondered whether a similar transamidation pathway also operates in
      the formation of Asn-tRNA in these organisms. Therefore we tested in S-100
      preparations of Lactobacillus bulgaricus, a gram-positive eubacterium, for the
      conversion by an amidotransferase of [14C]Asp-tRNA to [14C]Asn-tRNA. As no
      transamidation was observed, we searched for genes for asparaginyl-tRNA
      synthetase (AsnRS). Two DNA fragments (from different locations of the
      L.bulgaricus chromosome) were found each containing an ORF whose sequence
      resembled that of the Escherichia coli asnS gene. The derived amino acid
      sequences of the two ORFs (432 amino acids) were the same and 41% identical with
      E.coli AsnRS. When one of the ORFs was expressed in E.coli, it complemented the
      temperature sensitivity of an E.coli asnS mutant. S-100 preparations of this
      transformant showed increased charging of unfractionated L.bulgaricus tRNA with
      asparagine. Deletion of the 3'-terminal region of the L.bulgaricus AsnRS gene led
      to loss of its complementation and aminoacylation properties. This indicates that
      L.bulgaricus contains a functional AsnRS. Thus, the transamidation pathway
      operates only for Gin-tRNAGln formation in this organism, and possibly in all
      gram-positive eubacteria.

PMID- 8758991
TI  - Solid-phase synthesis of oligo-2-pyrimidinone-2'-deoxyribonucleotides and oligo-2
      pyrimidinone-2'-deoxyriboside methylphosphonates.
AB  - A synthetic method was developed for the synthesis of oligodeoxyribonucleotides
      and oligodeoxyribonucleoside methylphosphonates comprised exclusively of the
      fluorescent 2-pyrimidinone base for the first time. The method utilized the solid
      phase 2-cyanoethylphosphoramidite and methylphosphonamidite chemistry for
      internucleotide couplings and a baselabile oxalyl linkage to anchor the oligomers
      onto the CPG support. Cleavage of the oligomers from the support was effected by
      a short treatment of the support with 5% ammonium hydroxide in methanol at room
      temperature, without any degradation of the base-sensitive 2-pyrimidinone
      residues or the base-sensitive methylphosphonate backbone.

PMID- 8758992
TI  - Structural elements of the 3'-terminal coat protein binding site in alfalfa
      mosaic virus RNAs.
AB  - The 3'-terminal of the three genomic RNAs of alfalfa mosaic virus (AIMV) and
      ilarviruses contain a number of AUGC-motifs separated by hairpin structures.
      Binding of coat protein (CP) to such elements in the RNAs is required to initiate
      infection of these viruses. Determinants for CP binding in the 3'-terminal 39
      nucleotides (nt) of AIMV RNA 3 were analyzed by band-shift assays. From the 5'-
      to 3'-end this 39 nt sequence contains AUGC-motif 3, stem-loop structure 2
      (STLP2), AUGC-motif 2, stem-loop structure 1 (STLP1) and AUGC-motif 1. A
      mutational analysis showed that all three AUGC-motifs were involved in CP
      binding. Mutation of the A- and U-residues of motifs 1 or 3 had no effect on CP
      binding but similar mutations in motif 2 abolished CP binding. A mutational
      analysis of the stem of STLP1 and STLP2 confirmed the importance of these
      hairpins for CP binding. Randomization of the sequence of the stems and loops of
      STLP1 and STLP2 had no effect on CP binding as long as the secondary structure
      was maintained. This indicates that the two hairpins are not involved in sequence
      specific interactions with CP. They may function in a secondary structure
      specific interaction with CP and/or in the assembly of the AUGC-motifs in a
      configuration required for CP binding.

PMID- 8758993
TI  - Structure of a U.U pair within a conserved ribosomal RNA hairpin.
AB  - A conserved hairpin corresponding to nt 1057-1081 of large subunit rRNA
      (Escherichia coli numbering) is part of a domain targeted by antibiotics and
      ribosomal protein L11. The stem of the hairpin contains a U.U juxtaposition,
      found as either U.U or U.C in virtually all rRNA sequences. This hairpin has been
      synthesized and most of the aromatic and sugar protons were assigned by two
      dimensional proton NMR. Distances and sugar puckers deduced from the NMR data
      were combined with restrained molecular dynamics calculations to deduce
      structural features of the hairpin. The two U residues are stacked in the helix,
      form one NH3-O4 hydrogen bond and require an extended backbone conformation
      (trans alpha and gamma) at one of the U nucleotides. The hairpin loop, UAGAAGC
      closed by a U-A pair, is the same size as tRNA anticodon loops, but not as well
      ordered.

PMID- 8758994
TI  - Is the in-frame termination signal of the Escherichia coli release factor-2
      frameshift site weakened by a particularly poor context?
AB  - The synthesis of release factor-2 (RF-2) in bacteria is regulated by a high
      efficiency +1 frameshifting event at an in-frame UGA stop codon. The stop codon
      does not specify the termination of synthesis efficiently because of several
      upstream stimulators for frameshifting. This study focusses on whether the
      particular context of the stop codon within the frameshift site of the
      Escherichia coli RF-2 mRNA contributes to the poor efficiency of termination. The
      context of UGA in this recoding site is rare at natural termination sites in
      E.coli genes. We have evaluated how the three nucleotides downstream from the
      stop codon (+4, +5 and +6 positions) in the native UGACUA sequence affect the
      competitiveness of the termination codon against the frameshifting event.
      Changing the C in the +4 position and, separately, the A in the +6 position
      significantly increase the termination signal strength at the frameshift site,
      whereas the nucleotide in the +5 position had little influence. The efficiency of
      particular termination signals as a function of the +4 or +6 nucleotides
      correlates with how often they occur at natural termination sites in E.coli;
      strong signals occur more frequently and weak signals are less common.

PMID- 8758995
TI  - Unexpected anisotropy in substrate cleavage rates by asymmetric hammerhead
      ribozymes.
AB  - RNA substrates which form relatively short helices I and III with hammerhead
      ribozymes are generally cleaved more rapidly than substrates which create longer
      binding helices. We speculated that for optimum cleavage rates, one of the
      helices needed to be relatively weak. To identify this helix, a series of
      ribozymes and substrates of varying lengths were made such that in the complex,
      helices I and III consisted of 5 and 10 bp respectively or vice versa. In two
      independent systems, substrates in the complexes with the shorter helix I and
      longer helix III were cleaved one to two orders of magnitude more rapidly than
      those in the complexes with the longer helix I and shorter helix III. Similar
      results were obtained whether the numbers of base pairs in helices I and III were
      limited either by the length of the hybridizing arms of the ribozyme or the
      length of the substrate. The phenomenon was observed for both all-RNA and DNA
      armed ribozymes. Thus, a relatively short helix I is required for fast cleavage
      rates in pre-formed hammer-head ribozyme-substrate complexes. When helix III has
      10 bp, the optimum length for helix I is approximately 5 bp.

PMID- 8758996
TI  - The loop B domain is physically separable from the loop A domain in the hairpin
      ribozyme.
AB  - In order to understand the catalysis mechanism of the hairpin ribozyme, mutant
      ribozymes were constructed. The distance between the loop A domain and the loop B
      domain was extended by inserting various lengths of nucleotide linkers at the
      hinge region in cis mutants, or the domains were separated physically in a trans
      mutant. All the mutant ribozymes, including the trans mutant, could cleave
      substrate RNA at the predicted site. A cis mutant with a single nucleotide
      insertion exhibited cleavage activity about twice as high as that of the wild
      type (wt) ribozyme. The insertion of 2-5 nucleotides (nt) gradually reduced the
      activity to the level of the wt ribozyme. Insertion of a longer linker, up to 11
      nt, resulted in the reduction of activity to one half of that of the wt ribozyme.
      The ribozyme with a single nucleotide insertion at the hinge region seems to form
      a more suitable conformation for catalysis by three-dimensional fold-back of the
      loop B to loop A containing the cleavage site. The trans mutant, in which the A
      and B domains were physically separated, maintained a significant level of
      activity, suggesting that both domains are necessary for catalysis, but
      separable. These results demonstrate that interaction between the A and B domains
      results in catalysis.

PMID- 8758998
TI  - High-titer bicistronic retroviral vectors employing foot-and-mouth disease virus
      internal ribosome entry site.
AB  - Bicistronic retroviral vectors were constructed containing the foot-and-mouth
      disease virus (FMDV) internal ribosome entry site (IRES) followed by the coding
      region of beta-galactosidase (beta-gal) or therapeutic genes, with the selectable
      neomycin phosphotransferase gene under the control of the viral long terminal
      repeat (LTR) promoter. LNFX, a vector with a multiple cloning site 3' to foot-and
      mouth disease virus IRES, was used to construct vectors encoding rat
      erythropoietin (EP), rat granulocyte colony-stimulating factor (G-CSF), human
      adenosine deaminase (ADA) and beta-gal. In transduced primary rat vascular smooth
      muscle cells the cytokines were expressed at high levels, similar to those
      obtained from vectors employing the viral LTR promoter. LNFZ, a vector encoding
      beta-gal, had a 10-fold increase in titer over that of LNPoZ, a comparable vector
      containing the poliovirus (Po) internal ribosome entry site. Primary canine
      vascular smooth muscle cells infected with LNFZ and LNPoZ expressed similar
      activities of beta-gal and neomycin phosphotransferase (NPT). Overall, these
      vectors had titers between 10(6) and 2 x 10(7) c.f.u./ml, indicating that foot
      and-mouth disease virus IRES provides high-titer bicistronic vectors with high
      level two gene expression.

PMID- 8758997
TI  - Requirements for cleavage by a modified RNase P of a small model substrate.
AB  - M1 RNA, the catalytic RNA subunit of RNase P from Escherichia coli, has been
      covalently linked at its 3' terminus to oligonucleotides (guide sequences) that
      guide the enzyme to target RNAs through hybridization with the target sequences.
      These constructs (M1GS RNAs) have been used to determine some minimal features of
      model substrates. As few as 3 bp on the 3' side of the site of cleavage in a
      substrate complex and 1 nt on the 5' side are required for cleavage to occur. The
      cytosines in the 3' terminal CCA sequence of the model substrates are important
      for cleavage efficiency but not cleavage site selection. A purine (base-paired or
      not) at the 3' side of the cleavage site is important both for cleavage site
      selection and efficiency. M1GS RNAs provide both a simple system for
      characterization of the reaction governed by M1 RNA and a tool for gene therapy.

PMID- 8758999
TI  - The influence of base identity and base pairing on the function of the alpha
      sarcin loop of 23S rRNA.
AB  - The alpha-sarcin loop of large subunit rRNAs is one of the sites of interaction
      of elongation factors with the ribosome, and the target of the cytotoxins alpha
      sarcin and ricin. Using a genetic selection for increased frameshifting in a
      reporter gene, we have isolated a C --> U mutation at position 2666 in the alpha
      sarcin loop. In the NMR-derived structure of the loop, bases equivalent to 2666
      and 2654 are paired via a non-canonical base pairing interaction. Each of the
      three base substitutions at C2666 and A2654 was constructed by site-directed
      mutagenesis of a plasmid borne copy of the rrnB operon of Escherichia coli. Only
      the C2666 --> U and A2654 --> G mutations that resulted in the formation of
      canonical A-U and C-G base pairs respectively, increased the levels of stop codon
      readthrough and frameshifting. The effects of different base pair combinations at
      positions 2666 and 2654 on ribosome function were then tested by constructing and
      analyzing all possible base combinations at these sites. All A --> G base
      substitution mutations at position 2654 and C --> U substitutions at position
      2666 increased the levels of translational errors. However, these effects were
      greatest when G2654 and U2666 had the potential to engage in standard Watson
      Crick base pairing interactions. These data indicate that base identity as well
      as base pairing interactions are important for the function of this essential
      component of the large subunit rRNA.

PMID- 8759000
TI  - In vitro and in vivo function of the C-terminus of Escherichia coli single
      stranded DNA binding protein.
AB  - We constructed several deletion mutants of Escherichia coli single-stranded DNA
      binding protein (EcoSSB) lacking different parts of the C-terminal region. This
      region of EcoSSB is composed of two parts: a glycine and proline-rich sequence of
      approximately 60 amino acids followed by an acidic region of the last 10 amino
      acids which is highly conserved among the bacterial SSB proteins. The single
      stranded DNA binding protein of human mitochondria (HsmtSSB) lacks a region
      homologous to the C-terminal third of EcoSSB. Therefore, we also investigated a
      chimeric protein consisting of the complete sequence of the human mitochondrial
      single-stranded DNA binding protein (HsmtSSB) and the C-terminal third of EcoSSB.
      Fluorescence titrations and DNA-melting curves showed that the C-terminal third
      of EcoSSB is not essential for DNA-binding in vitro. The affinity for single
      stranded DNA and RNA is even increased by the removal of the last 10 amino acids.
      Consequently, the nucleic acid binding affinity of HsmtSSB is reduced by the
      addition of the C-terminus of EcoSSB. All mutant proteins lacking the last 10
      amino acids are unable to substitute wild-type EcoSSB in vivo. Thus, while the
      nucleic acid binding properties do not depend on an intact C-terminus, this
      region is essential for in vivo function. Although the DNA binding properties of
      HsmtSSB and EcoSSB are quite similar, HsmtSSB does not function in E.coli. This
      failure cannot be overcome by fusing the C-terminal third of EcoSSB to HsmtSSB.
      Thus differences in the N-terminal parts of both proteins must be responsible for
      this incompatibility. None of the mutants was defective in tetramerization.
      However, mixed tetramers could only be formed by proteins containing the same N
      terminal part. This reflects structural differences between the N-terminal parts
      of HsmtSSB and EcoSSB. These results indicate that the region of the last 10
      amino acids, which is highly conserved among bacterial SSB proteins, is involved
      in essential protein-protein interactions in the E.coli cell.

PMID- 8759001
TI  - Site-specific recombination by the beta protein from the streptococcal plasmid
      pSM19035: minimal recombination sequences and crossing over site.
AB  - The beta recombinase from the broad host range Grampositive plasmid pSM19035
      catalyzes intramolecular site-specific recombination between two directly or
      inversely oriented recombination sites in the presence of a chromatin-associated
      protein (Hbsu). The recombination site had been localized to a 447 bp DNA segment
      from pSM19035. This segment includes a 90 bp region that contains two adjacent
      binding sites (I and II) for beta protein dimers. Using in vitro recombination
      assays, we show that this 90 bp region is necessary and sufficient for beta
      protein-mediated recombination; this defines the six site as the region required
      for beta protein binding. The point of crossing over has been localized to the
      center of site I. Hbsu has a strong binding affinity for an unknown site located
      within the 447 bp segment containing the six site. We discuss the possibility
      that Hbsu recognizes an altered DNA structure, rather than a specific sequence,
      generated in the synaptic complex.

PMID- 8759002
TI  - In differentiating mouse myoblasts DNA methyltransferase is posttranscriptionally
      and posttranslationally regulated.
AB  - Upon the onset of mouse myoblast differentiation there is a rapid drop in DNA
      methyltransferase activity followed by a genome wide demethylation [Jost and Jost
      (1994) J. Biol. Chem. 269, 10040-10043]. Here we show by using specific
      antibodies directed against DNA methyltransferase that upon differentiation there
      was a rapid drop in nuclear DNA methyltransferase whilst the internal control
      histone H1 remained constant. The loss of nuclear methyltransferase was not due
      to a translocation of the enzyme from the nucleus to the cytoplasm where there
      was an increase in creatine phosphokinase protein. In vitro run on experiments
      carried out with growing and differentiating myoblast nuclei showed no difference
      in the rate of DNA methyltransferase mRNA synthesis. As measured by Northern blot
      hybridization the relative half life of DNA methyltransferase mRNA in growing and
      differentiating cells in the presence of Actinomycin D was 5 h and 1 h 30 min
      respectively, whereas in the same cells the half life of histone H4 mRNA was in
      both cases 80 min. As measured by a combination of pulse chase experiments with
      labeled leucine and immunoprecipitation, the relative half-life of DNA
      methyltransferase in growing and differentiating cells was approximately 18 h and
      4 h 30 min respectively.

PMID- 8759003
TI  - Transcription activation by GC-boxes: evaluation of kinetic and equilibrium
      contributions.
AB  - Basal and GC-box activated transcription were compared by various assays in order
      to learn the basis for an 8-fold difference observed under standard conditions.
      The time required for forming pre-initiation complexes and initiating and
      elongating RNA synthesis, and the extent of transcription reinitiation were found
      to be quite similar for basal and activated transcription, with complex formation
      being the slow step in both cases. The extent of activation was found to vary
      widely with the amount of template DNA used. Activated pre-initiation complexes
      were found to have a higher stability than basal complexes. The data are
      interpreted to indicate that GC-box elements do not stimulate the rate constants
      for critical steps in this system but rather increase the equilibrium constant
      for pre-initiation complex formation, probably by 10-30-fold.

PMID- 8759004
TI  - PairWise and SearchWise: finding the optimal alignment in a simultaneous
      comparison of a protein profile against all DNA translation frames.
AB  - DNA translation frames can be disrupted for several reasons, including: (i)
      errors in sequence determination; (ii) RNA processing, such as intron removal and
      guide RNA editing; (iii) less commonly, polymerase frameshifting during
      transcription or ribosomal frameshifting during translation. Frameshifts
      frequently confound computational activities involving homologous sequences, such
      as database searches and inferences on structure, function or phylogeny made from
      multiple alignments. A dynamic alignment algorithm is reported here which
      compares a protein profile (a residue scoring matrix for one or more aligned
      sequences) against the three translation frames of a DNA strand, allowing
      frameshifting. The algorithm has been incorporated into a new package, WiseTools,
      for comparison of biological sequences. A protein profile can be compared against
      either a DNA sequence or a protein sequence. The program PairWise may be used
      interactively for alignment of any two sequence inputs. SearchWise can perform
      combinations of searches through DNA or protein databases by a protein profile or
      DNA sequence. Routine application of the programs has revealed a set of database
      entries with frameshifts caused by errors in sequence determination.

PMID- 8759005
TI  - 1H NMR studies of the 5-(hydroxymethyl)-2'-deoxyuridine containing TF1 binding
      site.
AB  - The pyrimidine base 5-(hydroxymethyl)-2'-deoxyuridine (HmU) is a common
      nucleotide in SPO1 phage DNA. Numerous transcriptional proteins bind HmU
      containing DNA preferentially implicating a regulatory function of HmU. We have
      investigated the conformation and dynamics of d-(5'-CHmUCHmUACACGHmUGHmUAGAG-OH
      3')2 (HmU-DNA). This oligonucleotide mimics the consensus sequence of
      Transcription Factor 1 (TF1). The HmU-DNA was compared to the thymine-containing
      oligonucleotide. NOESY and DQF COSY spectroscopy provided resonance assignments
      of nonexchangeable and exchangeable protons, intranucleotide, internucleotide and
      intrastrand proton-proton distances, and dihedral angle constraints. Methylene
      protons of the hydroxymethyl group are nonequivalent protons and the
      hydroxymethyl group is not freely rotating. The hydroxymethyl group adopts a
      specific orientation with the OH group oriented on the 3' side of the plane of
      the base. Analysis of imino proton resonances and NOEs indicates additional end
      base pair fraying and a temperature-induced transition to a conformation in which
      the internal HmU-A base pairs are disrupted or have reduced lifetimes.
      Orientation of the hydroxymethyl group indicates the presence of internucleotide
      intrastrand hydrogen bonding between the HmU12C5 hydroxyl group and A13. All
      sugars in both DNAs show a C2'endo conformation (typical of B-DNA).

PMID- 8759006
TI  - A novel promoter sequence is involved in the oxidative stress-induced expression
      of the adult T-cell leukemia-derived factor (ADF)/human thioredoxin (Trx) gene.
AB  - Adult T cell leukemia-derived factor (ADF) is a human thioredoxin (Trx) and is a
      disulfide reducing protein with various biological functions. We found that
      expression of the ADF/Trx gene was increased by oxidative agents such as hydrogen
      peroxide, diamide and menadione in Jurkat cells. Analysis using a CAT expression
      vector plasmid under the control of the ADF/Trx gene promoter revealed that CAT
      gene expression in Jurkat cells was increased after exposure to oxidative agents.
      A series of deletion analyses showed that a region from -976 to -890 of the 5'
      flanking sequence was required for enhancement of ADF/Trx promoter activity
      against the oxidative agents. Gel mobility shift assay revealed the specific DNA
      binding activities to the sequences from -953 to -930 in the nuclear extracts
      from the Jurkat cells. The sequences in this region showed no homology with any
      known consensus sequences for DNA binding factors. It is suggested that ADF/Trx
      gene expression is enhanced through a novel cis-acting regulatory element
      responsive for the oxidative stress and a new factor(s) is involved in this
      oxidative stress responsive element.

PMID- 8759007
TI  - Mitochondrial DNA polymerase gamma is expressed and translated in the absence of
      mitochondrial DNA maintenance and replication.
AB  - Mitochondria are essential organelles in all eukaryotic cells where cellular ATP
      is generated through the process of oxidative phosphorylation. Protein components
      of the respiratory assembly are gene products of both mitochondrial and nuclear
      genes. The mitochondrial genome itself encodes several protein and nucleic acid
      components required for such oxidative phosphorylative processes, but the vast
      majority of genes encoding respiratory chain components are nuclear. Similarly,
      the processes of replication and transcription of mitochondrial DNA rely
      exclusively upon RNA and protein species encoded by nuclear genes. We have
      analyzed two key nuclear-encoded proteins involved in mitochondrial DNA
      replication and transcription as a function of the presence or absence of
      mitochondrial DNA. Mitochondrial DNA polymerase (DNA polymerase gamma), the
      nuclear-encoded enzyme which synthesizes mtDNA, is expressed and translated in
      cells devoid of mitochondrial DNA itself. In contrast, mitochondrial
      transcription factor A protein levels are tightly linked to the mtDNA status of
      the cell. These results demonstrate that the DNA polymerase gamma protein is
      stable in the absence of mitochondrial DNA, and that there appears to be no
      regulatory mechanism present in these cells to alter levels of this protein in
      the complete absence of mitochondrial DNA. Alternatively, it is possible that
      this enzyme plays an additional, as yet undefined, role in the cell, thereby
      mandating its continued production.

PMID- 8759008
TI  - Cloning and analysis of the genes encoding the type IIS restriction-modification
      system HphI from Haemophilus parahaemolyticus.
AB  - The genomic region encoding the type IIS restriction-modification (R-M) system
      HphI (enzymes recognizing the asymmetric sequence 5'-GGTGA-3'/5'-TCACC-3') from
      Haemophilus parahaemolyticus were cloned into Escherichia coli and sequenced.
      Sequence analysis of the R-M HphI system revealed three adjacent genes aligned in
      the same orientation: a cytosine 5 methyltransferase (gene hphIMC), an adenine N6
      methyltransferase (hphIMA) and the HphI restriction endonuclease (gene hphIR).
      Either methyltransferase is capable of protecting plasmid DNA in vivo against the
      action of the cognate restriction endonuclease. hphIMA methylation renders
      plasmid DNA resistant to R.Hindill at overlapping sites, suggesting that the
      adenine methyltransferase modifies the 3'-terminal A residue on the GGTGA strand.
      Strong homology was found between the N-terminal part of the m6A
      methyltransferasease and an unidentified reading frame interrupted by an
      incomplete gaIE gene of Neisseria meningitidis. The HphI R-M genes are flanked by
      a copy of a 56 bp direct nucleotide repeat on each side. Similar sequences have
      also been identified in the non-coding regions of H.influenzae Rd DNA. Possible
      involvement of the repeat sequences in the mobility of the HphI R-M system is
      discussed.

PMID- 8759009
TI  - Analysis of co-crystal structures to identify the stereochemical determinants of
      the orientation of TBP on the TATA box.
AB  - Possible stereochemical determinants of the orientation of TBP on the TATA box
      are discussed using the crystal coordinates of TBP-TATA complexes, which have
      been determined by other groups. The C-terminal half of the TBP beta-sheet
      interacts with the TATA site of the DNA, and the N-terminal half with the A-rich
      site, so that the two sites with distinct curvatures produce a unique fit.
      Although chemical contacts take place between one side of the beta-sheet and the
      DNA minor groove, the interaction seems to be facilitated indirectly by the
      characteristics of the other side of the beta-sheet and the DNA major groove.
      Thus, Ala71, Leu162 and Pro190 differentiate the curvature of the beta-sheet in
      the N- and C-halves. The methyl positions in the DNA major groove modulate the
      bendability of the two DNA sites by using differences in the rolling capacity of
      TA and AT compared with PyT, and in the shifting capacity of AT compared with TT.
      The deformations of the first steps (TA and PyT) in the two sites are the largest
      and thus are important for the overall bending of the DNA. The differences
      between the two DNA sites are greatest at the second steps (AT and TT) and so
      these are important for determining the orientation of TBP.

PMID- 8759010
TI  - Analysis and suppression of DNA polymerase pauses associated with a trinucleotide
      consensus.
AB  - We have studied a novel class of DNA sequences that cause DNA polymerases to
      pause. These sequences have the central consensus Py-G-C and are not necessarily
      adjacent to hairpins in the DNA template. Since most consensus sequences do not
      cause pauses under standard conditions, additional template features must exist
      that make it difficult to incorporate nucleotides at these positions. We believe
      that these pauses result from constraints that make the conformation change
      involved in nucleotide selection more difficult. These pauses can obscure parts
      of DNA sequencing ladders and prevent DNA amplification by the polymerase chain
      reaction. The addition of betaine, and some related compounds, relieves these
      pauses.

PMID- 8759013
TI  - A new universal linker for solid phase DNA synthesis.
AB  - A method is described as an alternative to the use of nucleoside pre
      functionalized supports for DNA synthesis. The procedure should allow the
      generation of 3'-OH terminal moieties of any natural or modified DNA fragment
      using a single derivatized solid support material. The method utilizes 1-O-(4,4'
      dimethoxytrityl)-2- O-succinoyl-3-N-allyloxycarbonylpropane immobilized on amino
      propyl CPG followed by subsequent coupling of unit phosphoramidites. Work up is
      accomplished by removal of the 3-N-allyloxycarbonyl group [Pd(0) at 50 degrees C
      for 15 min] followed by cleavage under very mild conditions (aqueous TEAA/NH3
      buffer pH 10, room temperature) to release the desired product. The mechanism is
      believed to involve nucleophilic attack of the linker-derived amino group on the
      3'-phosphate triester, followed by elimination of the desired product. DNA
      synthesis with the new support and with classical nucleotide synthesis supports
      have been performed, and the products shown to be identical. Further proof of
      product integrity was given by MALDI mass spectral studies and the efficacy of
      DNA primers made with the new support in PCR amplification.

PMID- 8759012
TI  - Cloning and characterization of Sse9I DNA-methyltransferase recognizing 5'-AATT
      3'.
AB  - The gene from Sporosarcina species 9D encoding Sse9I DNA-methyltransferase
      (M.Sse9I) was cloned and expressed in Escherichia coli. The recombinant plasmid
      pMSse-1 contains the M.Sse9I gene 1086 bp in length, corresponding to a protein
      of 362 amino acid residues. M.Sse9I recognizes the tetranucleotide sequence 5'
      AATT-3' and modifies the second adenine within the recognition sequence. The
      amino acid sequence of M.Sse9I was compared with those of other methylases.
      According to mutual positions of four conservative domains the new enzyme belongs
      to a subgroup of D12 class. This subgroup includes Sse9I, CviAII, NlaIII and N
      terminal domains of LlaI, FokI and StsI DNA-methyltransferases.

PMID- 8759011
TI  - A dominant transcriptional silencer located 5' to the human T-cell receptor V
      beta 2.2 gene segment which is activated in cell lines of thymic phenotype.
AB  - We have identified a transcriptional regulatory sequence located 5' to the human
      T-cell receptor V beta 2.2 promoter. The upstream part of this sequence acts as a
      transcriptional activator in the three cell lines, Jurkat, MOLT4 and HSB2, which
      all have a thymic phenotype. The downstream part of the sequence exerts a
      dominant silencing activity in the Jurkat and MOLT4 cell lines, but not in the
      immature HSB2 cell line. The silencing sequence binds nuclear factor(s).
      Mutations of nucleotides in a short stretch of sequence, demonstrating
      methylation interference, abolish both the factor binding and the silencing
      effect. Replacement of the silencing element by a homologous sequence found 5' to
      the human V beta 8.1 segment, leads to a protein binding pattern which shows some
      DNA- protein specific complexes identical to those observed with the V beta 2.2
      sequence. Interestingly, binding of nuclear factors to the V beta 2.2 silencing
      sequence is also observed using thymic extracts, but not using extracts from
      samples enriched for CD34+ cells, PBL, EBV cell lines or the HeLa cell line.

PMID- 8759015
TI  - Sequence analysis and characterization of stutter products at the tetranucleotide
      repeat locus vWA.
AB  - The PCR amplification of tetranucleotide short tandem repeat (STR) loci typically
      produces a minor product band 4 bp shorter than the corresponding main allele
      band; this is referred to as the stutter band. Sequence analysis of the main and
      stutter bands for two sample alleles of the STR locus vWA reveals that the
      stutter band lacks one repeat unit relative to the main allele. Sequencing
      results also indicate that the number and location of the different 4 bp repeat
      units vary between samples containing a typical verses low proportion of stutter
      product. The results also suggest that the proportion of stutter product relative
      to the main allele increases as the number of uninterrupted core repeat units
      increases. The sequence analysis and results obtained using various DNA
      polymerases appear to support the slipped strand displacement model as a
      potential explanation for how these stutter products are generated.

PMID- 8759014
TI  - Characterization of the single-strand-specific BPV-1 origin binding protein, SPSF
      I, as the HeLa Pur alpha factor.
AB  - SPSF I and II are two cellular proteins which bind specifically to single
      stranded DNA. SPSF I and II binding sites are found in the minimal origin of
      replication of BPV-1 DNA and near the P2 promoter of the cellular c-myc gene. DNA
      binding properties of the two proteins to single-stranded oligonucleotides of
      different lengths and sequences were quantified by determination of DNA-binding
      constants. The binding constant of SPSF proteins to the lower strand of the BPV-1
      origin was determined to be 1.5 x 10(-10) M-1. Peptide sequences derived from
      purified SPSF I and II revealed the identity of at least one of the SPSF proteins
      with the so-called HeLa Pur alpha factor. The HeLa Pur alpha factor was
      identified previously by virtue of its capacity to bind to purine-rich strands of
      the PUR element found in initiation zones of DNA replication [Bergemann, A.D.,
      Ma,Z.-W. and Johnson, E.M. (1992) Mol. Cell. Biol. 12, 5673-5682]. Expression of
      the Pur cDNA confirmed the identity of the Pur alpha protein with the 42 kDa SPSF
      I protein. Analysis of several Pur alpha cDNA clones revealed the existence of an
      extended 3'-untranslated region in all Pur mRNAs.

PMID- 8759016
TI  - E2A basic-helix-loop-helix transcription factors are negatively regulated by
      serum growth factors and by the Id3 protein.
AB  - Id3, a member of the Id multigene family of dominant negative helix-loop-helix
      transcription factors, is induced sharply in murine fibroblasts by serum growth
      factors. To identify relevant targets of Id3 activity, the yeast two-hybrid
      system was used to identify proteins that dimerize with Id3. Four murine cDNAs
      were identified in the screen, all of which encode helix-loop-helix proteins:
      E12, E47, ALF1 and Id4. Co-immunoprecipitation assays confirm that Id3 interacts
      with E12, E47 and two alternative splice products of ALF1 in vitro. Id3 disrupts
      DNA binding by these proteins in vitro and blocks transcriptional activation by
      these factors in cultured murine cells. Additionally, Id3 shows evidence of
      interacting with the related proteins E2-2 and MyoD, but not c-Myc. These results
      suggest that Id3 can function as a general negative regulator of the basic-helix
      loop-helix family of transcription factors exemplified by the 'E' proteins and
      MyoD. Although it was previously suspected that E2A is constitutively expressed,
      our data indicate that E2A is induced in quiescent fibroblasts, by growth factor
      withdrawal but not by contact inhibition of cell proliferation. These
      observations extend the role of Id3 in the functional antagonism of E2A-class
      transcription factors, and suggest that E2A proteins may mediate growth
      inhibition.

PMID- 8759017
TI  - A viral genome containing an unstable aflatoxin B1-N7-guanine DNA adduct situated
      at a unique site.
AB  - A problem that has hindered the study of the biological properties of certain DNA
      adducts, such as those that form at the N7 atoms of purines, is their extreme
      chemical lability. Conditions are described for the construction of a single
      stranded genome containing the chemically and thermally labile 8,9-dihydro-8- (N7
      guanyl)-9-hydroxyaflatoxin B1 (AFB1-N7-Gua) adduct, the major DNA adduct of the
      potent liver carcinogen aflatoxin B1 (AFB1). A 13mer oligonucleotide,
      d(CCTCTTCGAACTC), was allowed to react with the exo-8,9-epoxide of AFB1 to form
      an oligonucleotide containing a single AFB1-N7-Gua (at the underlined guanine).
      This modified 13mer was 5'-phosphorylated and ligated into a gap in an M13
      bacteriophage genome generated by annealing a 53mer uracil-containing scaffold to
      M13mp7L2 linearized by EcoRI. Following ligation, the scaffold was enzymatically
      removed with uracil DNA glycosylase and exonuclease III. The entire genome
      construction was complete within 3 h and was carried out at 16 degrees C, pH 6.6,
      conditions determined to be optimal for AFB1-N7-Gua stability. Characterization
      procedures indicated that the AFB1-N7-Gua genome was approximately 95% pure with
      a small (5%) contamination by unmodified genome. This construction scheme should
      be applicable to other chemically or thermally unstable DNA adducts.

PMID- 8759018
TI  - De novo generation of simple sequence during gene amplification.
AB  - Mammalian cells that have undergone gene amplification and/or gene rearrangement
      have been used as resources to gain insight into the questions of chromosome
      structure and dynamics. The multidrug resistant murine cell line J7.V2-1 has been
      shown previously to contain two distinct forms of the highly amplified mdr2 gene,
      a member of the mouse gene family responsible for the multidrug resistant (MDR)
      phenotype [Kirschner, L. S. (1995) DNA Cell Biol. 14, 47-59]. Characterization of
      both forms of the gene revealed that one form corresponded to the wild-type
      structure of the gene, whereas the other represented a rearrangement.
      Investigation of this altered gene demonstrated a deletion of 1.6 kb of the wild
      type sequence, and replacement of this region with a poly(AT) tract that appears
      to have been generated de novo. Analysis of the native sequence in this region
      demonstrated the absence of repetitive elements, but was notable for the presence
      of two long stretches of polypurine: polypyrimidine strand asymmetry. Analysis of
      mdr2 transcripts in this cell line revealed that nearly all of the mRNA is
      transcribed from the rearranged form of the gene. This message is unable to code
      for a functional mdr2 gene product, owing to a deletion of the fourth exon during
      this event. Mechanisms of the rearrangement, as well as the significance of this
      curious effect on transcription, are discussed.

PMID- 8759019
TI  - In vitro expansion of GGC:GCC repeats: identification of the preferred strand of
      expansion.
AB  - The human fragile-X syndrome, a major cause of inherited mental retardation, is
      associated with expansion of the trinucleotide repeat GGC:GCC. Repetitive
      sequences in DNA are subject to slippage during catalysis by DNA polymerases. We
      characterized the extent of slippage of synthetic GGC:GCC repeats by various DNA
      polymerases: Taq DNA polymerase, Klenow fragment of DNA polymerase I, DNA
      Sequence, DNA polymerase-alpha and polymerase-beta, as well as HIV reverse
      transcriptase. All of these enzymes were found to expand GGC:GCC repeats, with
      the most extensive expansion exhibited by Taq DNA polymerase. Starting with a
      template and primer, each 15 nucleotides (nt) in length, the product of one round
      of synthesis by Taq polymerase is as long as 250 nt. Sequence analysis of cloned
      DNA fragments expanded by Taq polymerase indicates that expansion involves
      multiple triplet additions and that it is asymmetric. The asymmetric distribution
      of terminal nucleotides in the expanded product is consistent with active
      expansion of the GCC strand and passive additions onto the GGC strand. The
      preferential elongation and expansion of the GCC strand was confirmed in studies
      utilizing longer repeats within a single-stranded M-13 template.

PMID- 8759020
TI  - Structural features and stability of an RNA triple helix in solution.
AB  - A 30 nt RNA with a sequence designed to form an intramolecular triple helix was
      analyzed by one-and two-dimensional NMR spectroscopy and UV absorption
      measurements. NMR data show that the RNA contains seven pyrimidine-purine
      pyrimidine base triples stabilized by Watson-Crick and Hoogsteen interactions.
      The temperature dependence of the imino proton resonances, as well as UV
      absorption data, indicate that the triple helix is highly stable at acidic pH,
      melting in a single sharp transition centered at 62 degrees C at pH 4.3. The
      Watson-Crick and Hoogsteen pairings are disrupted simultaneously upon melting.
      The NMR data are consistent with a structural model where the Watson-Crick paired
      strands form an A-helix. Results of model building, guided by NMR data, suggest a
      possible hydrogen bond between the 2' hydroxyl proton of the Hoogsteen strand and
      a phosphate oxygen of the purine strand. The structural model is discussed in
      terms of its ability to account for some of the differences in stability reported
      for RNA and DNA triple helices and provides insight into features that are likely
      to be important in the design of RNA binding compounds.

PMID- 8759022
TI  - Aminotetralin drugs and D3 receptor functions. What may partially selective D3
      receptor ligands tell us about dopamine D3 receptor functions?
AB  - The dopamine D3 receptor gene was identified by Sokoloff and colleagues in 1990.
      This finding rapidly gained the interest of the scientific community because this
      unexpected dopamine receptor subtype may play an important role in the
      antipsychotic activity of neuroleptic drugs. It recognizes most neuroleptics with
      a high affinity, and its brain distribution is restricted mainly to the ventral
      part of the striatal complex. However, the characterization and the subsequent
      identification of functions of the D3 receptor were hampered initially by at
      least four important factors that are still partially unresolved: (1) the absence
      of selective drugs that can discriminate between the D2 and D3 receptor subtype
      functions in vivo, (2) the lack of apparent coupling with GTP-dependent proteins,
      (3) the absence of effects on second messenger systems, and (4) the low level of
      expression of this receptor in brain tissue; these factors have contributed to
      tempering the interest of scientists. However, this situation has begun to change
      with the identification of [3H]7-hydroxy-N,N-(di-n-propyl)-2-aminotetralin ([3H]7
      OH-DPAT), the first selective ligand for the dopamine D3 receptor. Although its
      binding selectivity for the D3 versus the D2 receptor is somewhat artificial, the
      potentially important impact of identification of a function for the D3 receptor
      encouraged scientists to use this aminotetralin compound for in vivo studies
      with, however, limited success. This commentary is focused on the impact and
      controversies generated by the use of 7-OH-DPAT and its congeners, on new
      conceptual views that may arise from this research, and on what partially
      selective D3 receptor ligands may tell us about dopamine D3 receptor functions.

PMID- 8759023
TI  - Involvement of the beta-diketone moiety in the antioxidative mechanism of
      tetrahydrocurcumin.
AB  - We examined the inhibitory effects of curcumin and tetrahydrocurcumin (THC), one
      of the major metabolites of curcumin, on the lipid peroxidation of erythrocyte
      membrane ghosts induced by tertbutylhydroperoxide. The results demonstrated that
      THC showed a greater inhibitory effect than curcumin. To investigate the
      mechanism of antioxidative activity, we examined the effects of several
      inhibitors, such as antioxidant enzymes, hydroxyl radical scavengers, 1O2
      quencher, and chelating agents for metal ions. Given that all inhibitors failed
      to inhibit membrane peroxidation, THC must scavenge radicals such as tert-butoxyl
      radical and peroxyl radical. To clarify the antioxidative mechanism of THC, in
      particular the role of the beta-diketone moiety, dimethylated THC was incubated
      with peroxyl radicals generated by thermolysis of 2,2'-azobis(2,4
      dimethylvaleronitrile). Four oxidation products were detected, three of which
      were identified as 3,4-dimethoxybenzoic acid, 3',4'-dimethoxyacetophenone, and 3
      (3,4-dimethoxyphenyl)-propionic acid. The fourth oxidation product seems to be an
      unstable intermediate, and its detailed structure has not been determined. These
      results suggest that the beta-diketone moiety of THC must exhibit antioxidative
      activity by cleavage of the C-C bond at the active methylene carbon between two
      carbonyls in the beta-diketone moiety. Because THC is one of the major
      metabolites of curcumin, it may also exhibit the same physiological and
      pharmacological properties as the active form of curcumin in vivo by means of the
      beta-diketone moiety as well as phenolic hydroxy groups.

PMID- 8759021
TI  - Functional interaction between a RARE and an AP-2 binding site in the regulation
      of the human HOX A4 gene promoter.
AB  - HOX A genes are induced in a temporal fashion after retinoic acid (RA) treatment
      in non-N-ras-transformed PA-1 human teratcarcinoma cells. However, In N-ras
      transformed PA-1 cells, RA-Induced expression of HOX A genes is delayed. The mRNA
      for the transcriptional activator AP-2 is overexpressed in these ras-transformed
      cells, but AP-2 transcriptional activity is inhibited relative to non ras
      transformed PA-1 cells. Constitutive expression of AP-2 mimics the effect of ras
      by transforming cells and inhibiting differentiation in culture. We analyzed 4 kb
      of the human HOX A4 gene promoter and identified seven putative AP-2-binding
      sites in the DNA sequence. Transcription assays with variably sized HOX A4
      promoter reporter constructs revealed that a 365 bp region of the promoter, -2950
      to -3315 relative to the mRNA start, controls RA responsiveness and ras-mediated
      inhibition of HOX A4 activity. This region contains an AP-2 binding site and a
      RARE. Elimination of the AP-2 site by site-directed mutagenesis demonstrated that
      the AP-2 site is involved in RA-mediated transcriptional activation of the human
      HOX A4 promoter in combination with the RA receptor response element (RARE). In N
      ras-transformed cells, low HOX A4 promoter activity results from ras inhibition
      of AP-2 transactivation.

PMID- 8759024
TI  - Two activities of the immunosuppressive metabolite of leflunomide, A77 1726.
      Inhibition of pyrimidine nucleotide synthesis and protein tyrosine
      phosphorylation.
AB  - Previous studies have demonstrated that the active metabolite of leflunomide, A77
      1726 [N-(4-trifluoromethylphenyl-2-cyano-3-hydroxycrotoamide)], is capable of
      inhibiting the activities of tyrosine kinases and dihydroorotate dehydrogenase
      (DHO-DHase). In the present study, we define the relative contribution of these
      activities to the ability of A77 1726 to inhibit proliferation of the murine
      leukemia cell line LSTRA. A77 1726 inhibited LSTRA cell growth and proliferation
      (IC50 = 10-30 microM); this inhibition, however, could be reversed by the
      addition of exogenous uridine, suggesting that the anti-proliferative activity of
      A77 1726 may be due to inhibition of de novo pyrimidine nucleotide synthesis.
      Quantitation of nucleotide levels revealed that A77 1726, at an IC50 of about 10
      microM, selectively inhibited pyrimidine nucleotide but not purine nucleotide
      synthesis. In vitro enzyme assays confirmed that A77 1726 directly inhibited the
      activity of DHO-DHase, the fourth enzyme in the de novo pathway of pyrimidine
      nucleotide synthesis (IC50 = 220 nM). LSTRA cells overexpress p56lck and have
      elevated levels of tyrosine phosphorylated intracellular proteins. A77 1726
      reduced the intracellular levels of tyrosine phosphorylated proteins with
      relatively high IC50 values ranging from 50 to 100 microM. A77 1726 also
      inhibited p56lck activity in LSTRA membrane preparation and immunoprecipitates;
      the IC50 values for inhibition of immunoprecipitated p56lck autophosphorylation
      and exogenous substrate histone 2B were 80 and 40 microM, respectively. The anti
      tyrosine phosphorylation activity of A77 1726 was not affected by uridine. These
      studies therefore demonstrate the two activities of A77 1726: inhibition of
      pyrimidine nucleotide synthesis and interference with tyrosine phosphorylation.

PMID- 8759025
TI  - Evidence for reversible sequestration of morphine in rat liver.
AB  - The residence of morphine in the systemic circulation is prolonged despite a high
      systemic clearance, suggestive of significant extravascular sequestration. The
      present study was conducted to test the hypothesis that morphine binds
      significantly in tissues, and that the liver plays an important role in morphine
      binding. [14C]Morphine was administered to male Sprague-Dawley rats 55 min before
      unlabeled morphine or saline. Blood 14C increased immediately after injection of
      unlabeled morphine; the area under the blood concentration-time curve (AUC) for
      14C increased approximately 2-fold after morphine compared with saline injection.
      Residual radioactivity in the liver was lower in morphine-treated rats than in
      controls, suggesting that unlabeled drug displaced [14C]morphine (or a
      metabolite) from binding sites. To examine this phenomenon more directly, a
      recirculating isolated perfused liver system was employed. [14C]Morphine was
      added to the perfusate reservoir 15 min before unlabeled morphine or saline;
      perfusate and bile samples were collected for 120 min. Upon termination of
      perfusion, the liver was fractionated to identify the hepatic subcellular
      fraction(s) in which morphine was sequestered. The perfusate AUC for
      [14C]morphine was increased approximately 2-fold in response to unlabeled drug,
      consistent with the in vivo experiment. Morphine was associated preferentially
      with the cytosolic fraction, and [14C]morphine in all relevant fractions was
      reduced after administration of unlabeled morphine. In contrast, unlabeled drug
      had no influence on derived [14C]morphine-3-beta,D-glucuronide. These data are
      consistent with significant, reversible binding of morphine in hepatic tissue.

PMID- 8759026
TI  - Inhibition of topoisomerase II by ICRF-193, the meso isomer of 2,3-bis(2,6
      dioxopiperazin-4-yl)butane. Critical dependence on 2,3-butanediyl linker absolute
      configuration.
AB  - The bis(2,6-dioxopiperazine)s are a structurally and mechanistically unique class
      of topoisomerase II inhibitors that do not bind DNA and that do not stabilize
      topoisomerase II-DNA strand passing intermediates ("cleavable complexes"). The
      most effective topoisomerase II inhibitor in the bis(2,6-dioxopiperazine) series
      is ICRF-193 (meso or S*, R* isomer), with a meso 2,3-butanediyl linker connecting
      the dioxopiperazine rings. The two enantiomeric diastereomers, (R,R) and (S,S),
      of ICRF-193 possessing the two optically active 2,3-butanediyl linkers have been
      prepared from their respective optically pure 2,4-diaminobutanes via 2,3
      diaminobutane-N,N,N',N'-tetraacetic acid, esterification, and imide formation.
      Both in vivo and in vitro assays for catalytic inhibition of topoisomerase II
      were employed to show that the (S,S)- and (R,R)-isomers are almost inactive as
      topoisomerase II inhibitors. The data indicate that the meso stereochemistry of
      the alkanediyl linker is crucial for activity and provides additional evidence
      that the cytotoxicity of the bis(2,6-dioxopiperazine)s is due to their ability to
      inhibit topoisomerase II.

PMID- 8759027
TI  - Novel bisquinoline antimalarials. Synthesis, antimalarial activity, and
      inhibition of haem polymerisation.
AB  - We report the synthesis of two series of novel bisquinoline compounds that
      inhibit the growth of both chloroquine-sensitive and chloroquine-resistant
      strains of Plasmodium falciparum. To study the molecular basis of the action of
      these novel antimalarial drugs, we examined their ability to inhibit haem
      polymerisation in the presence and absence of parasite extracts. The level of
      antimalarial potency was correlated with the level of inhibition of haem
      polymerisation, suggesting that these bisquinolines exert their antimalarial
      activity by antagonising the sequestration of toxic haem moieties.

PMID- 8759028
TI  - Hepatic extraction ratio of 5-fluorouracil in rats. Dose dependence and effect of
      uracil and interleukin-2.
AB  - The hepatic extraction ratios (EH) of 5-fluorouracil (FUra) in rats were studied
      to clarify the disposition of FUra in the liver. The EH of FUra in rats at
      infusion rates ranging from 0.375 to 3 mg/kg/min decreased from 0.750 to 0.225.
      The EH of values of tegafur, a pro-drug of FUra, were 0.076 to 0.103 over the
      range of infusion rates, 0.577 to 4.616 mg/kg/min, and were much lower than those
      of FUra. The EH of FUra at an infusion rate of 0.375 mg/kg/min combined with
      uracil (0.323 mg/kg/min) was 0.646, which was significantly lower than that of
      FUra alone, 0.750 (P < 0.001). The EH of FUra combined with interleukin-2 (IL-2)
      at an infusion rate of 7500 U/kg/min was significantly higher than that of FUra
      alone (P < 0.01). The dose dependence of the EH of FUra and the effects of uracil
      and IL-2 on the EH of FUra corresponded with clinical findings. These results
      suggest that this experimental model in rats may be useful for predicting the
      clinical pharmacokinetics and efficacy of FUra. We also studied the effect of IL
      2 on the EH of mitomycin C (MMC). The EH of MMC combined with IL-2 was higher
      than that of MMC alone, but the difference was not significant.

PMID- 8759029
TI  - Differential modulation of protein kinase C isozymes in rat parotid acinar cells.
      Relation to amylase secretion.
AB  - We investigated the expression, distribution, and activation parameters of
      protein kinase C (PKC) isozymes in isolated rat parotid acinar cells. By
      analyzing cellular extracts by western blot analysis and for isozyme-specific
      RNA, the Ca(2+)-independent PKC-delta, -epsilon, and -zeta were detected in the
      cytosolic, particulate (plasma membrane), and nuclear fractions of unstimulated
      cells, whereas the Ca(2+)-dependent PKC-alpha was confined to the cytosolic and
      particulate fractions. The expressed isozymes showed distinct responses to
      phorbol 12-myristate 13-acetate (PMA), thymeleatoxin, and cell surface receptor
      agonists with respect to translocation from cytosol to particulate fraction and
      nucleus, as well as sensitivity to down-regulation caused by prolonged exposure
      to PMA (3-20 hr). The marked susceptibility to down-regulation displayed by PKC
      alpha and -delta was accompanied by an enhanced secretory response to
      norepinephrine as compared with control cells. Further, the selective PKC
      inhibitors Ro 31-8220 and CGP 41,251 also produced a concentration-dependent
      enhancement of norepinephrine-induced amylase secretion. Our findings suggest
      that PKC-alpha or -delta plays a negative modulatory role, rather than an
      obligatory role, in amylase secretion. Also, the localization and redistribution
      of PKC-epsilon and -delta to the nucleus by PKC activators imply that one or both
      of these isozymes may regulate such processes as cellular proliferation and/or
      differentiation.

PMID- 8759030
TI  - Oxidation of vitamin E, vitamin C, and thiols in rat brain synaptosomes by
      peroxynitrite.
AB  - Peroxynitrite is formed by the reaction of superoxide with nitric oxide, an
      important neurotransmitter. Incubation of rat brain synaptosomes with
      peroxynitrite resulted in the consumption of antioxidant substances such as alpha
      tocopherol, ascorbate, and thiols. Membrane cholesterol was not oxidized under
      the same conditions. alpha-Tocopherol and ascorbate in synaptosomes were oxidized
      very rapidly by peroxynitrite. In contrast, previous reports in the literature
      have shown that peroxynitrite treatment did not oxidize tocopherol in human
      plasma. Peroxynitrite in sufficient concentrations oxidized all of the tocopherol
      and ascorbate in synaptosomes. Thus, the oxidant is able to diffuse to the
      different membranes in synaptosomes and oxidize tocopherol in all of them. alpha
      Tocopherol is converted quantitatively to tocopherolquinone during the oxidation.
      Significant amounts of thiols (at least 30% of the total thiols) do not seem to
      be accessible to oxidation by peroxynitrite. However, the concentration of thiols
      is much higher than those of tocopherol and ascorbate. Addition of the hydroxyl
      radical quenchers benzoate or mannitol or the enzymes superoxide dismutase or
      catalase (alone or together) did not affect the oxidation of tocopherol and
      ascorbate by peroxynitrite, whereas cysteine and glutathione blocked the
      oxidation. Therefore, reactive oxygen species may not be directly involved as
      intermediates in oxidations induced by peroxynitrite. The latter is a potent
      oxidizing agent that can oxidize substances such as tocopherols, ascorbate, and
      thiols in the immediate vicinity of its formation. The antioxidant nutrients
      ascorbate and tocopherol could play important roles in protecting brain from
      oxidative damage induced by peroxynitrite.

PMID- 8759031
TI  - Atypical cytochrome P450 induction profiles in glomerular mesangial cells at the
      mRNA and enzyme level. Evidence for CYP1A1 and CYP1B1 expression and their
      involvement in benzo[a]pyrene metabolism.
AB  - Recent studies in this laboratory have shown that benzo[a]pyrene (BaP) modulates
      growth factor-related gene expression and proliferation of renal glomerular
      mesangial cells (GMCs) in vitro. Because many of the toxic and biochemical
      effects of this polycyclic aromatic hydrocarbon are mediated through oxidative
      metabolism, the present studies were conducted to examine the patterns of
      cytochrome P450IA1 (CYP1A1) and P4501B1 (CYP1B1) inducibility in mesangial cells
      and the molecular consequences of this response. Exposure of cultured GMCs to BaP
      (30 microM) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 10 nM) for 24 hr
      induced CYP1A1 mRNA levels, a response abolished by cotreatment with 10 microM
      cycloheximide. The pattern of hydrocarbon inducibility was atypical in that BaP
      was a more effective inducer of CYP1A1 gene expression than TCDD, and both
      hydrocarbons induced aryl hydrocarbon hydroxylase (AHH) activity, but not
      ethoxyresorufin-O-deethylase activity. Cotreatment with alpha-naphthoflavone
      (alpha NF, 1 microM) or ellipticine (ELLIP, 0.1 nM) only partially inhibited the
      induction of AHH activity by BaP (30 microM). BaP and TCDD also induced
      expression of the CYP1B1 protein and the pattern of induction was comparable to
      that observed for CYP1A1. Treatment of GMCs with 30 microM BaP was associated
      with the formation of eight DNA adducts, and their occurrence could be inhibited
      by pretreatment with alpha NF (1 microM), but not ELLIP (0.1 nM). These results
      demonstrate that CYP1A1 and CYP1B1-related activities are induced in GMCs by BaP
      and TCDD and this induction is associated with metabolism of BaP to reactive
      intermediates that bind covalently to DNA.

PMID- 8759032
TI  - Inhibition of fibroproliferation by pentoxifylline. Activity of metabolite-1 and
      lack of role of adenosine receptors.
AB  - We have reported previously that pentoxifylline and adenosine decrease platelet
      derived growth factor- (PDGF) stimulated fibroproliferation. To determine the
      role of adenosine receptors in the inhibition of fibroproliferation observed with
      pentoxifylline, we used a non-selective adenosine receptor antagonist, 8
      phenyltheophylline, and specific A1 and A2 adenosine receptor antagonists. If the
      A2 receptor, which is present on fibroblasts, mediates the inhibition of
      fibroproliferation which occurs with pentoxifylline, then pretreatment of
      fibroblasts with receptor antagonists prior to the addition of pentoxifylline
      should prevent the action of pentoxifylline. The results indicated that
      pretreatment of fibroblasts with 8-phenyltheophylline (100 microM) did not alter
      the inhibitory effect of pentoxifylline on PDGF-stimulated fibroproliferation.
      These results argue against a mechanism involving inhibition of adenosine
      reuptake as the mechanism for pentoxifylline's effect in this system. 8
      Phenyltheophylline also did not alter the effect of pentoxifylline on baseline
      proliferation, suggesting that these effects of pentoxifylline are not mediated
      by adenosine receptors. Pentoxifylline is metabolized to several metabolites
      including 1-(5-hydroxyhexyl)-3,7-dimethylxanthine (metabolite-1). Metabolite-1
      significantly reduced PDGF-stimulated fibroproliferation and was as effective as
      pentoxifylline. The combination of pentoxifylline and metabolite-1 had an
      additive effect. Metabolite-1 and pentoxifylline also reduced baseline
      proliferation. Preincubation of fibroblasts with 8-phenyltheophylline did not
      prevent the inhibitory action of metabolite-1 on PDGF-stimulated proliferation or
      on basal proliferation of fibroblasts, suggesting that the action of metabolite-1
      on fibroproliferation was not mediated by adenosine receptors. Results using A1
      and A2 adenosine receptor antagonists further suggest that the effect of
      pentoxifylline was not mediated by adenosine receptors.

PMID- 8759033
TI  - Effects of sphingosine stereoisomers on P-glycoprotein phosphorylation and
      vinblastine accumulation in multidrug-resistant MCF-7 cells.
AB  - To investigate the role of protein kinase C (PKC) in the regulation of multidrug
      resistance and P-glycoprotein (P-gp) phosphorylation, the natural isomer of
      sphingosine (SPH), D-erythro sphingosine (De SPH), and its three unnatural
      stereoisomers were synthesized. The SPH isomers showed similar potencies as
      inhibitors of in vitro PKC activity and phorbol binding, with IC50 values of
      approximately 50 microM in both assays. Treatment of multidrug-resistant MCF-7ADR
      cells with SPH stereoisomers increased vinblastine (VLB) accumulation up to 6
      fold at 50 microM but did not alter VLB accumulation in drug-sensitive MCF-7 wild
      type (WT) cells or accumulation of 5-fluorouracil in either cell line. Phorbol
      dibutyrate treatment of MCF-7ADR cells increased phosphorylation of P-gp, and
      this increase was inhibited by prior treatment with SPH stereoisomers. Treatment
      of MCF-7ADR cells with SPH stereoisomers decreased basal phosphorylation of the P
      gp, suggesting inhibition of PKC-mediated phosphorylation of P-gp. Most drugs
      that are known to reverse multidrug resistance, including several PKC inhibitors,
      have been shown to directly interact with P-gp and inhibit drug binding. SPH
      stereoisomers did not inhibit specific binding of [3H] VLB to MCF-7ADR cell
      membranes or [3H]azidopine photoaffinity labeling of P-gp or alter P-gp ATPase
      activity. These results suggest that SPH isomers are not substrates of P-gp and
      suggest that modulation of VLB accumulation by SPH stereoisomers is associated
      with inhibition of PKC-mediated phosphorylation of P-gp.

PMID- 8759034
TI  - Modulation of nicotine-evoked [3H]dopamine release from rat striatal synaptosomes
      by voltage-sensitive calcium channel ligands.
AB  - The calcium channel subtypes mediating nicotine-evoked [3H]dopamine release from
      rat striatal synaptosomes were probed with L-, N-, and P-type calcium channel
      ligands. Responses to nicotine were blocked by the peptides omega-conotoxin GVIA
      and omega-agatoxin IVA. The affinity constants for these compounds were
      consistent with their actions at N- and P-type channels, respectively. Together,
      these channels mediate at least 90% of the calcium-dependent response to
      nicotine. The L-type antagonists nifedipine, verapamil, and nicardipine were also
      effective blockers of nicotine-evoked release with maximal effects of 80-100%
      inhibition. However, these effects occurred at concentrations 2-3 orders of
      magnitude higher than those necessary to block L-type channels. Moreover, Bay
      K8644, an L-type agonist, also blocked nicotine-evoked release. Together, these
      findings argue strongly against the involvement of L-type channels.

PMID- 8759035
TI  - Specific binding of nitroglycerin to coronary artery microsomes. Evidence of a
      vascular nitrate binding site.
AB  - The vasodilating action of organic nitrates, such as nitroglycerin (NTG), is
      thought to be mediated through metabolic conversion to nitric oxide (NO) in
      vascular smooth muscle. Although the pertinent enzyme(s) that carries out this
      crucial step has not been identified, previous studies have shown that the
      primary enzymatic site is located within cellular membrane fractions. In these
      studies, we examined the binding of [14C]NTG to microsomal fractions from bovine
      coronary arteries. Specific binding was linearly related to protein
      concentration, and binding equilibrium was reversible, reached equilibrium within
      1 hr, and remained stable for 4 hr at 25 degrees. Competition experiments with
      unlabeled NTG demonstrated the presence of two binding sites of differing
      affinities (high-affinity site: Bmax 24.1 +/- 0.9 pmol/mg protein, Kd 554 +/- 22
      pM; low-affinity site: Bmax 79.0 +/- 2.9 pmol/mg protein, Kd 151 +/- 3 microM).
      Both of the thiol alkylators 1-chloro-2,4-dinitrobenzene and N-ethylmaleimide
      were found to inhibit [14C]NTG binding, as well as enzymatic generation of NO
      from NTG, in a concentration-dependent manner. Competition of [14C]NTG was also
      observed with five other organic nitrate vasodilators, and the degree of
      competition was linearly related to the in vitro vaso-relaxing potencies of these
      agents. Parallel experiments also showed that in the absence of thiol cofactor,
      the enzymatic production of NO from NTG was antagonized competitively by less
      potent organic nitrates. Intact blood vessel experiments using rat aorta also
      showed that the presence of isosorbide dinitrate (ISDN), at concentrations that
      did not induce relaxation alone, caused a slight but significant shift in the
      relaxation potency of NTG (EC25 9 +/- 2 versus 28 +/- 7 nM, in the presence and
      absence of 0.3 microM ISDN, respectively; P < 0.05). These results demonstrate
      the presence of specific binding of organic nitrates to microsomal proteins in
      vascular smooth muscle, and the observed binding is apparently related to
      enzymatic conversion to NO and the vasodilating properties of these compounds.

PMID- 8759036
TI  - Kinetic study of cutaneous and subcutaneous distribution following topical
      application of [7,8-14C]rac-alpha-lipoic acid onto hairless mice.
AB  - To diminish oxidative injury, topically applied antioxidants must reach
      susceptible cells. alpha-Lipoic acid is a potent thiol antioxidant that might be
      useful for skin protection; therefore, its skin penetration kinetics were
      assessed. The cutaneous and subcutaneous distributions of [7,8-14C]rac-alpha
      lipoic acid were studied in anesthetized hairless mice after application of a 5%
      solution in propylene glycol for 0.5 to 4 hr. The mice were killed; then the skin
      was washed, and the stratum corneum was removed by 10 cellophane tape strippings.
      A punch biopsy of the frozen, stripped skin was sectioned, and amounts of [14C]
      alpha-lipoic acid were determined in strippings and slices of epidermis (4 x 5
      microns), dermis, and subcutaneous fat (10 x 10 microns, 20 x 20 microns). The
      rate of [14C]-alpha-lipoic acid absorption into skin was constant by 30 min (0.10
      +/- 0.01 nmol/cm2/min); maximum skin concentrations were reached by 2 hr. The
      [14C]-alpha-lipoic acid penetration kinetics into the first layer of the stratum
      corneum predicted its penetration through the stratum corneum and subsequent
      percutaneous absorption (r2 = 0.96, P < 0.02). Cutaneous absorption of unlabeled
      alpha-lipoic acid and its reduction to the more potent antioxidant form,
      dihydrolipoic acid, were also demonstrated, using HPLC analysis with
      electrochemical detection. In conclusion, alpha-lipoic acid topically applied to
      skin penetrated readily, and was reduced to dihydrolipoic acid. Thus, alpha
      lipoic acid could potentiate skin antioxidant protection.

PMID- 8759037
TI  - Collateral sensitivity to the bisdioxopiperazine dexrazoxane (ICRF-187) in
      etoposide (VP-16)-resistant human leukemia K562 cells.
AB  - Etoposide (VP-16)-resistant K562 cells (K/VP.5) were 26-fold resistant to VP-16,
      due in part to a reduction in DNA topoisomerase II (topoisomerase II) protein
      levels. Compared with parental K562 cells, VP-16-resistant K/VP.5 cells were
      found to be 3.4-fold more sensitive to the effects of dexrazoxane (ICRF-187), a
      topoisomerase II inhibitor that does not stabilize topoisomerase II-DNA covalent
      complexes. In contrast, K/VP.5 cells were 4.0-fold cross-resistant to merbarone
      and showed no cross-resistance to fostriecin, two other topoisomerase II
      inhibitors that do not stabilize topoisomerase II-DNA covalent complexes.
      Preincubation with ICRF-187 resulted in greater inhibition of subsequent VP-16
      induced topoisomerase II-DNA covalent complexes in K/VP.5 cells than in K562
      cells. Conversely, preincubation with merbarone resulted in less inhibition of VP
      16-induced topoisomerase II-DNA covalent complexes in K/VP.5 cells than in
      parental K562 cells. Preincubation with forstriecin had little effect on VP-16
      induced topoisomerase II-DNA covalent complex formation in either cell line. The
      onset rates for ICRF-187 inhibition of VP-16-induced topoisomerase II-DNA complex
      formation were similar in sensitive and resistant cells. In addition, ICRF-187
      had a comparable concentration-dependent inhibitory effect on the topoisomerase
      II catalytic activities of K562 and K/VP.5 cells. Together, our results indicate
      that collateral sensitivity to ICRF-187 in K/VP.5 cells is due to decreased
      topoisomerase II protein levels rather than to an alteration in topoisomerase II
      activity. Furthermore, results suggest that ICRF-187, merbarone, and fostriecin
      have different mechanisms of action that can be studied effectively in K/VP.5 and
      K562 cells.

PMID- 8759038
TI  - Stimulation of cyclic AMP accumulation and phosphoinositide hydrolysis by M3
      muscarinic receptors in the rat peripheral lung.
AB  - The effects of oxotremorine-M (oxo-M), a muscarinic agonist, on cyclic AMP (cAMP)
      accumulation in slices of the rat peripheral lung were investigated. Oxo-M
      stimulated cAMP accumulation in a concentration-dependent manner with an EC50
      value of 4.2 microM and a maximal effect of 2.4 +/- 0.39-fold over basal. In the
      presence of forskolin (25 microM), the maximal effect of oxo-M was increased to
      14.1 +/- 4.0-fold over basal. Forskolin alone caused a 5.9 +/- 2.2-fold increase
      in cAMP relative to basal; therefore, the combination of both drugs was more than
      additive. The effects of oxo-M on cAMP accumulation were unaffected by
      tetrodotoxin, indicating that the action of oxo-M was not mediated by neuronal
      release of neurotransmitters. Oxo-M had a small inhibitory effect on cAMP in a
      homogenate preparation, indicating that the stimulatory response to oxo-M in
      slices of the lung is not due to direct stimulation of adenylyl cyclase.
      Characterization of the oxo-M potentiation of forskolin-stimulated cAMP
      accumulation using different muscarinic antagonists yielded calculated pKB values
      that agreed with binding affinities for the M3 subtype. Oxo-M elicited
      phosphoinositide hydrolysis in the lung, and the nature of the antagonism of this
      response was also consistent with that expected for an M3-mediated response. cAMP
      accumulation in the presence of oxo-M (100 microM), forskolin (12 microM), or
      both drugs combined was inhibited by indomethacin (1 microM). These results
      demonstrate that the M3 receptor stimulates cAMP accumulation and
      phosphoinositide hydrolysis in the rat peripheral lung, and the mechanism for
      cAMP stimulation may involve arachidonic acid metabolites.

PMID- 8759039
TI  - Activation of a human peroxisome proliferator-activated receptor by the antitumor
      agent phenylacetate and its analogs.
AB  - The aromatic fatty acid phenylacetate and its analogs induce tumor cytostasis and
      differentiation in experimental models. Although the underlying mechanisms of
      action are not clear, effects on lipid metabolism are evident. We have now
      examined whether these compounds, structurally similar to the peroxisome
      proliferator clofibrate, affect the human peroxisome proliferator-activated
      receptor (hPPAR), a homolog of the rodent PPAR alpha, a transcriptional factor
      regulating lipid metabolism and cell growth. Gene transfer experiments showed
      activation of hPPAR, evident by the increased expression of the reporter gene
      chloramphenicol acetyltransferase linked to PPAR-response element from either the
      rat acyl-CoA oxidase or rabbit CYP4A6 genes. The relative potency of tested drugs
      in the co-transfection assay was: 4-iodophenylbutyrate > 4-chlorophenylbutyrate >
      clofibrate > phenylbutyrate > naphthylacetate > 2,4-D > 4-chlorophenylacetate >
      phenylacetate >> indoleacetate. Phenylacetylglutamine, in which the carboxylic
      acid is blocked, was inactive. The ability of the aromatic fatty acids to
      activate PPAR was confirmed in vivo, as CYP4A mRNA levels increased in
      hepatocytes of treated rats. Further studies using human prostate carcinoma,
      melanoma, and glioblastoma cell lines showed a tight correlation between drug
      induced cytostasis, increased expression of the endogenous hPPAR, and receptor
      activation documented in the gene-transfer model. These results identify
      phenylacetate and its analogs as a new class of aromatic fatty acids capable of
      activating hPPAR, and suggest that this nuclear receptor may mediate tumor
      cytostasis induced by these drugs.

PMID- 8759040
TI  - Effect of acute and chronic intermittent hypoxia on DNA topoisomerase II alpha
      expression and mitomycin C-induced DNA damage and cytotoxicity in human colon
      cancer cells.
AB  - Recently, we reported that alterations in topoisomerase II (topo II) activity
      appear to contribute to mitomycin C (MMC) resistance in HT-29R13 human colon
      cancer cells under aerobic conditions. In this study, the expression of topo II
      alpha and topo II beta in parent HT-29 and MMC resistant variant HT-29R13 cells
      was investigated under aerobic, acute hypoxic (after 4 hr in 95% N2, 5% CO2 <
      0.01% O2), and chronic intermittent hypoxic (after 4 hr hypoxia/day x 7 days)
      conditions. Acute hypoxia induced topo II alpha mRNA and protein, effects that
      were more pronounced in HT-29 cells. Chronic intermittent hypoxia caused a
      decrease in topo alpha mRNA and protein, changes that were again more pronounced
      in HT-29 cells. The observed changes in topo II alpha protein were associated
      with parallel changes in topo II activity under all conditions tested. Topo II
      beta mRNA was expressed at a very low level in both cell lines under aerobic and
      hypoxic conditions. Compared with cells under aerobic conditions, HT-29 cells
      were more sensitive to MMC under acute hypoxia but more resistant under chronic
      intermittent hypoxia. In contrast, the senstivity of HT-29R13 cells was unchanged
      under acute hypoxia, but the cells were more resistant under chronic intermittent
      hypoxia. Under all conditions tested, the degree of cytotoxicity corresponded to
      the frequency of MMC-induced DNA cross-links and topo II alpha protein levels and
      activity. Our results demonstrated that MMC cytotoxicity in hypoxic cells is
      highly dependent upon the type of hypoxia and the cell type. Hypoxia has
      significant effects on topo II alpha expression in HT-29 and HT-29R13 cells which
      correlate with MMC cytotoxicity.

PMID- 8759041
TI  - Noradrenaline stimulation of high-affinity GTPase activity in membranes from rat
      aorta and caudal artery.
AB  - The ability of noradrenaline (NA) to stimulate increases in high-affinity GTPase
      activity in sarcolemma-enriched rat aorta and caudal artery membranes was
      examined in the present study. In aortic membranes, NA significantly (P < 0.05; N
      = 5) increased the Vmax from a basal value of 103 +/- 29 to 156 +/- 38 pmol
      Pi/min/mg protein, but did not affect the Km which was 0.32 +/- 0.08 microM in
      the absence and 0.58 +/- 0.16 microM in the presence of NA. However, in caudal
      artery membranes, NA significantly (P < 0.05; N = 6) increased both the Vmax and
      the Km from basal values of 69 +/- 12 pmol Pi/min/mg protein and 0.24 +/- 0.05
      microM, respectively, to 205 +/- 54 pmol Pi/min/mg protein and 1.01 +/- 0.25
      microM, respectively. Removing the endothelium from both artery preparations did
      not alter significantly basal GTPase activity or the magnitude of the increase
      stimulated by NA. Prazosin significantly inhibited NA-stimulated increases in
      GTPase activity in membranes from endothelium-denuded caudal artery and aorta,
      and in endothelium-intact caudal artery membranes. However, yohimbine
      significantly inhibited NA-stimulated increases in GTPase activity only in
      preparations from endothelium-intact caudal arteries. Therefore, in endothelium
      intact caudal artery membranes, NA stimulated increases in GTPase activity that
      were apparently mediated by both alpha 1-adrenoceptors and alpha 2-adrenoceptors,
      while in endothelium-denuded aortic and caudal artery membranes this increase was
      mediated solely by alpha 1-adrenoceptors. Western blotting of these arteries
      confirmed the presence of both Gi alpha 2,3 and Gq/11 alpha, which are candidates
      for mediating the alpha 1-adrenoceptor-stimulated increases in GTPase activity.

PMID- 8759042
TI  - The processing-speed theory of adult age differences in cognition.
AB  - A theory is proposed to account for some of the age-related differences reported
      in measures of Type A or fluid cognition. The central hypothesis in the theory is
      that increased age in adulthood is associated with a decrease in the speed with
      which many processing operations can be executed and that this reduction in speed
      leads to impairments in cognitive functioning because of what are termed the
      limited time mechanism and the simultaneity mechanism. That is, cognitive
      performance is degraded when processing is slow because relevant operations
      cannot be successfully executed (limited time) and because the products of early
      processing may no longer be available when later processing is complete
      (simultaneity). Several types of evidence, such as the discovery of considerable
      shared age-related variance across various measures of speed and large
      attenuation of the age-related influences on cognitive measures after statistical
      control of measures of speed, are consistent with this theory.

PMID- 8759043
TI  - Goodness of visual regularities: a nontransformational approach.
AB  - Until recently, the transformational approach provided the only available formal
      analysis of visual regularities like repetition and mirror symmetry. This
      theoretical study presents a new analysis, based on the recently developed
      concept of holographic regularity. This concept applies to the intrinsic
      character of regularity and specifies the unique formal status of perceptually
      relevant regularities. The crucial point is that the two analyses imply the same
      structure for repetition but a different structure for mirror symmetry.
      Transformationally, mirror symmetry is an all-or-nothing property, whereas
      holographically, it is a graded property. This difference pervades the
      understanding of both perfect regularities and perturbed regularities. Whereas
      the transformational approach explains hardly any goodness phenomenon, the
      holographic approach explains a wide variety of goodness phenomena in a coherent
      way that is ecologically plausible as well.

PMID- 8759044
TI  - Neurofunctional mechanisms in autism.
AB  - Behavioral impairments in autism are theorized to result from abnormal neuronal
      organization in brain development generating 4 systemically related
      neurofunctional impairments: (a) canalesthesia, wherein abnormal hippocampal
      system function "canalizes" sensory records, disrupting integration of
      information; (b) impaired assignment of the affective significance of stimuli,
      wherein abnormal amygdaloid system function disrupts affect association; (c)
      asociality, wherein impaired oxytocin system function flattens social bonding and
      affiliativeness; and (d) extended selective attention, wherein abnormal
      organization of temporal and parietal polysensory regions yields aberrant
      overprocessing of primary representations. This model proposes that complex human
      behaviors may be guided by multiple overlapping neural mechanisms.

PMID- 8759045
TI  - Monitoring and control processes in the strategic regulation of memory accuracy.
AB  - When people are allowed freedom to volunteer or withhold information, they can
      enhance the accuracy of their memory reports substantially relative to forced
      report performance. A theoretical framework addressing the strategic regulation
      of memory reporting is put forward that delineates the mediating role of
      metamemorial monitoring and control processes. Although the enhancement of memory
      accuracy is generally accompanied by a reduction in memory quantity, experimental
      and simulation results indicate that both of these effects depend critically on
      (a) accuracy incentive and (b) monitoring effectiveness. The results are
      discussed with regard to the contribution of meta-memory processes to memory
      performance, and a general methodology is proposed that incorporates these
      processes into the assessment of memory-accuracy and memory-quantity performance.

PMID- 8759046
TI  - Orthographic processing in visual word recognition: a multiple read-out model.
AB  - A model of orthographic processing is described that postulates read-out from
      different information dimensions, determined by variable response criteria set on
      these dimensions. Performance in a perceptual identification task is simulated as
      the percentage of trials on which a noisy criterion set on the dimension of
      single word detector activity is reached. Two additional criteria set on the
      dimensions of total lexical activity and time from stimulus onset are
      hypothesized to be operational in the lexical decision task. These additional
      criteria flexibly adjust to changes in stimulus material and task demands, thus
      accounting for strategic influences on performance in this task. The model
      unifies results obtained in response-limited and data-limited paradigms and helps
      resolve a number of inconsistencies in the experimental literature that cannot be
      accommodated by other current models of visual word recognition.

PMID- 8759047
TI  - Reconciling simplicity and likelihood principles in perceptual organization.
AB  - Two principles of perceptual organization have been proposed. The likelihood
      principle, following H. L. F. von Helmholtz (1910/1962), proposes that perceptual
      organization is chosen to correspond to the most likely distal layout. The
      simplicity principle, following Gestalt psychology, suggests that perceptual
      organization is chosen to be as simple as possible. The debate between these two
      views has been a central topic in the study of perceptual organization. Drawing
      on mathematical results in A. N. Kolmogorov's (1965) complexity theory, the
      author argues that simplicity and likelihood are not in competition, but are
      identical. Various implications for the theory of perceptual organization and
      psychology more generally are outlined.

PMID- 8759048
TI  - On the reality of cognitive illusions.
AB  - The study of heuristics and biases in judgement has been criticized in several
      publications by G. Gigerenzer, who argues that "biases are not biases" and
      "heuristics are meant to explain what does not exist" (1991, p. 102). The article
      responds to Gigerenzer's critique and shows that it misrepresents the authors'
      theoretical position and ignores critical evidence. Contrary to Gigerenzer's
      central empirical claim, judgments of frequency--not only subjective
      probabilities--are susceptible to large and systematic biases. A postscript
      responds to Gigerenzer's (1996) reply.

PMID- 8759049
TI  - Correlation between cell differentiation stage, types of invasion, and
      hematogenous metastasis in experimental rhabdomyosarcomas.
AB  - Cancer malignancy is directly related to invasiveness and metastasis and
      inversely related to the degree of tumor differentiation. The relation between
      the stage of cell differentiation and the types of invasion leading to metastasis
      is not entirely clear. Intramuscularly transplanted rat rhabdomyosarcomas are
      good models to study cell differentiation, invasion, and metastasis. Rat
      rhabdomyosarcoma cell lines (SMF-Ai, SMF-Da, and RMS-B and its clones) with
      defined invasive and metastatic potentials have been established. The stage of
      myogenic differentiation was evaluated morphologically and by
      immunohistochemistry. Invasiveness was evaluated according to the infiltration of
      muscle fibers and basal lamina. The SMF-Ai line is highly invasive and
      metastatic. It is composed of premyoblasts that were involved in intercellular,
      translaminar, and transcellular invasion of muscle fibers. The SMF-Da line is
      noninvasive and nonmetastatic. It is composed of myoblasts. The RMS-B line and
      its clones were at different stages of differentiation and they differed in their
      invasiveness and metastatic potentials. In highly invasive and metastatic clones
      (RMS-Bg and RMS-Bc), premyoblasts were involved in translaminar invasion. Clones
      composed of myoblasts, rhabdomyoblasts, and myotubes only showing intercellular
      invasion did not present hematogenous metastasis. Our results demonstrate a
      correlation between premyoblastic stage of differentiation and translaminar
      invasion. The presence of translaminar invasion is directly related to
      hematogenous metastatic ability of rat rhabdomyosarcomas.

PMID- 8759050
TI  - Organotypic culture of human gallbladder epithelium.
AB  - We have modified methods of growing human gallbladder epithelial cells in
      monolayer and organotypic culture. These cells were grown in the presence of
      fetal bovine serum and with coculture of feeder layers of human gallbladder
      fibroblasts. Human gallbladders were obtained from cholecystectomy specimens, and
      the cells were dissociated with trypsin/EDTA. Cells, which were grown with feeder
      layer on collagen-coated plates in the presence of 10% FBS, grew rapidly and
      formed islands of cuboidal cells with morphology typical of epithelial cells in
      culture. They could be passaged up to four times. The cells were also
      successfully grown by organotypic technique producing a monolayer of tall,
      columnar, palisade, epithelial cells. These cells, both in monolayer and in
      organotypic culture, were positive to antibodies for simple epithelial keratin
      and negative to antibody for vimentin or any of the mesenchymal antibodies. These
      cells respond to agonists (prostaglandin E2, isoproterenol) by the intracellular
      generation of cAMP. Secreted mucin on the apical surface stained strongly with
      periodic acid-Schiff. Organotypic culture of human gallbladder epithelium may
      serve as a cell preparation for the study of pathobiology of columnar epithelial
      cells.

PMID- 8759051
TI  - Hypolipidemic and antiatherosclerotic effects of a novel ACAT inhibitor, HL-004,
      in stroke-prone spontaneously hypertensive rats.
AB  - The hypolipidemic and antiatherosclerotic effects of a novel acyl CoA:cholesterol
      acyltransferase (ACAT) inhibitor, HL-004, were studied in stroke-prone
      spontaneously hypertensive rats (SHRSP). SHRSP were administered 0.01-0.09% HL
      004 mixed in a hypercholesterolemic (HC) diet for 50 days. HL-004 reduced the
      cholesterol and triglyceride levels in serum, as well as those in the liver,
      small intestine, and aorta, in a dose-dependent manner. HC diet-induced severe
      fat deposition in the mesenteric arteries, which is characteristic of SHRSP, was
      also decreased by HL-004. The ACAT activity of the small intestine and liver was
      decreased by HL-004. In particular, liver ACAT activity was significantly low in
      SHRSP given 0.09% HL-004, compared to that of normal animals. These results
      suggest that HL-004 is a systemic ACAT inhibitor and that the ACAT inhibition in
      the intestine, liver, and aorta is involved in the hypolipidemic and
      antiatherosclerotic effects of HL-004.

PMID- 8759052
TI  - Distribution of cisplatin in bone marrow cells: quantitative X-ray imaging.
AB  - The distribution of cisplatin in freeze-dried cryosections of rabbit bone marrow
      cells was measured with an imaging system. Cisplatin contains a single atom of
      platinum per molecule which allowed the concentration of the drug to be measured
      throughout the cryosections. This technique was chosen because it does not
      require the separation of cells into homogeneous subpopulations. X-ray imaging
      measured not only the distribution of the element labeling the drug, but also
      other elements which were used to follow the effect of the drug on membrane ion
      transport. In samples incubated for 10 hr in cisplatin a high selectivity in the
      uptake of this drug was observed. Only a few of the large early cells were found
      to accumulate this drug, while in the smaller more mature cells platinum could
      not be detected. Most of the platinum accumulated in the cytoplasm and was not
      evenly distributed. Cells containing high levels of platinum lost their
      cytoplasmic potassium and gained extracellular sodium and chloride. In some cases
      cells that contain lower concentrations of platinum with normal levels of
      potassium were found, indicating that the alteration of the membrane permeability
      or the inhibition of the K/Na pump did not occur during the initial accumulation
      of the drug. This membrane permeability or pump change requires the accumulation
      of high concentrations of the drug, resulting in the loss of potassium and the
      gain of sodium.

PMID- 8759053
TI  - Tissue repair in the iris in experimental autoimmune uveoretinitis.
AB  - Our previous work on rats with S-antigen-induced experimental autoimmune
      uveoretinitis showed iris tissue changes involving infiltration of inflammatory
      cells, destruction of the iris architecture, and breakdown of the blood-retinal
      barrier. The present study reports the remarkable ability of the iris to
      regenerate during the postinflammatory period. The iris regenerates 50% of its
      architecture by Day 20 postimmunization. The number of lymphocytes and
      polymorphonuclear leukocyte (PMNs) was relatively high at this stage. Many
      capillaries showed abnormal endothelial cells. Unmyelinated nerve axons were
      often seen near blood vessels. The iris stroma was edematous. By Day 30,
      approximately 95% of the iris had regenerated, the number of lymphocytes and PMNs
      decreased, and the number of macrophages increased. Most capillaries looked
      normal and numerous axons in different stages of myelination were apparent. The
      stroma, the dilator muscle, and the posterior epithelium were almost completely
      restored. By Day 45, the iris appeared to be virtually normal. Most striking was
      the abundance of myelinated nerve axons located near blood vessels. Type I
      collagen immunoreactivity in vascular endothelial cells increased from Day 20 to
      Day 60 postimmunization, suggesting that blood vessel endothelial cells may play
      a role in collagenization of the iris stroma.

PMID- 8759054
TI  - Keratinocyte growth factor and receptor mRNA expression in benign and malignant
      human prostate.
AB  - We have examined whether keratinocyte growth factor (KGF) and its receptor are
      expressed in normal, fetal, and prostate cancer cells since KGF may play a role
      in the growth of adenocarcinomas. In situ hybridization studies with digoxigenin
      labeled oligonucleotides (anti-sense and sense controls) were employed to examine
      KGF and KGF receptor mRNA expression in prostate cancer. We found that the KGF
      and KGF receptor genes were faintly expressed in the stromal and epithelial
      cells, respectively, in both fetal (n = 6) and normal adult prostate (n = 6)
      tissues examined. In 10 benign prostatic hyperplasias (BPH), and in low- and high
      grade prostatic carcinoma (32 total), both the KGF gene and the receptor mRNA
      were expressed in the glandular epithelial cells. KGF was also expressed by the
      stromal cells in BPH and low-grade carcinoma. Computer assisted system analysis
      indicated that the intensity of epithelial labeling by both probes was increased
      in high Gleason score carcinomas ( > 8) and in metastatic nodules. We interpret
      the data to mean that the paracrine loop in normal prostate may be replaced by an
      autocrine loop in BPH and adenocarcinomas.

PMID- 8759055
TI  - Heat shock in vivo induces Mallory body formation in drug primed mouse liver.
AB  - Perturbations in keratin intermediate filament organization and Mallory body (MB)
      formation are associated with alcoholic hepatitis. Inducible heat shock proteins
      (HSPs) are expressed in a variety of liver diseases including alcoholic liver
      disease. Therefore, we investigated whether heat shock protein induction can lead
      to MB formation. Mice were primed by a 5-month feeding of griseofulvin (GF) or
      diethyl 1,4-dehydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC) followed by
      drug withdrawal for 1 month. The animals were then subjected to an in vivo heat
      shock treatment or sham heat treatment. Liver morphology, HSP expression, liver
      regeneration (PCNA-labeled nuclei), and MB formation were monitored during a 7
      day posttreatment period. Numerous MBs developed in the livers of mice exposed to
      GF or DDC for 5 months, but very few small MBs remained after 1-month withdrawal
      of either drug. No MBs were found at Day 1 post heat shock, whereas numerous MBs
      were observed at Day 7. The frequency of PCNA-labeled nuclei increased during the
      same period. At Day 1 posttreatment, a variable liver centrilobular necrosis was
      observed accompanied by a prominent increase in HSP-25 and HSP70 expression, but
      HSP-90 expression was not increased. In drug-primed mouse liver, a heat shock
      treatment induces the expression of specific HSPs prior to the formation of MBs,
      indicating that HSP expression may play a role in the pathogenesis of MB
      formation. We speculate that this role is through the protein unfolding function
      of HSP, which leads to the aggregation of the cytokeratins to form MBs as well as
      to polyubiquitin binding to these proteins in a manner analogous to amyloid
      formation.

PMID- 8759056
TI  - Antidote for America's leading pediatric disease.

PMID- 8759057
TI  - Acknowledgement of your research sponsor. It pays to advertise.

PMID- 8759058
TI  - Angiotensin-converting enzyme gene polymorphism. What to do about all the
      confusion.

PMID- 8759059
TI  - Reversing endothelial dysfunction with ACE inhibitors. A new trend.

PMID- 8759060
TI  - The atrial flutter reentrant circuit. Additional pieces of the puzzle.

PMID- 8759061
TI  - Should Fontan fenestrations be closed with coils?

PMID- 8759062
TI  - Transcatheter coil occlusion of surgical fenestration after Fontan operation.
AB  - BACKGROUND: Fenestration of the Fontan circulation that results in a residual
      right-to-left shunt has improved operative survival rates among high-risk
      patients. Late closure of the fenestration by use of a transcatheter umbrella
      device has achieved separation of the systemic and pulmonary venous circulations,
      "completing" the Fontan pathway. Because use of umbrella devices is restricted,
      many institutions continue to perform only nonfenestrated Fontan procedures.
      METHODS AND RESULTS: Five children 3.5 to 8.3 years old (mean, 5.1 years)
      underwent cardiac catheterization 0.5 to 24 months (mean, 10 months) after
      operation for the purpose of occluding a persistently patent Fontan fenestration.
      Once candidacy was determined, an 8-mm x 10-cm Gianturco coil was delivered to
      straddle the fenestration with established techniques for coil occlusion of
      patent ductus arteriosus. Complete occlusion occurred in 4 of 5 patients, in 2 of
      the 4 before they left the catheterization laboratory. One patient had a residual
      angiographic shunt but had complete closure within 24 hours by echocardiography.
      In 1 patient who had a residual shunt at 24 hours, the fenestration was
      completely closed at 1 month after coil placement. One patient had residual
      shunting at 2 months but saturations have increased 15% to 17% since coil
      placement. No embolizations (early or late), clinical hemolysis, thromboembolic
      events, or hemodynamic deterioration occurred among patients during 1- to 14
      month follow-up periods. CONCLUSIONS: A persistently patent fenestration after
      Fontan operation may be closed with a Gianturco coil. This universally available
      alternative to umbrella devices may make the fenestrated Fontan a more appealing
      option to centers that had not previously considered its use.

PMID- 8759063
TI  - Low-temperature mapping predicts site of successful ablation while minimizing
      myocardial damage.
AB  - BACKGROUND: Temperatures near 50 degrees C can cause reversible loss of
      excitability in myocardial cells. METHODS AND RESULTS: Low-temperature, short
      duration applications of radiofrequency energy were used to determine the
      adequacy of electrophysiological mapping of accessory pathway (AP) locations in
      15 patients at 27 target sites using a closed-loop, temperature-controlled
      generator set to 50 degrees C. Energy was delivered until evidence of conduction
      block, or for a maximum of 10 seconds. If AP block occurred, a full 70 degrees C
      set point radiofrequency application was delivered to the same site. In the
      absence of AP block, tests with higher temperature settings (60 degrees C and 70
      degrees C) were delivered to determine if inadequate temperature or catheter
      position led to failure of the initial 50 degrees C test. At 15 successful target
      sites where permanent AP block was achieved, the 50 degrees C test resulted in AP
      block in 14 (93%). Conduction returned in 13 of 14 APs after radiofrequency power
      was turned off. The time to block for the 70 degrees C applications was
      significantly shorter than for the 50 degrees C tests, and the peak temperature
      achieved was significantly higher. At unsuccessful sites where permanent AP block
      was not achieved, no block was induced with 11 of 12 tests at 50 degrees C, 6 of
      6 tests at 60 degrees C, and 1 of 2 tests at 70 degrees C, suggesting that
      failure was due to incorrect catheter position. The sensitivity and positive
      predictive values of a 50 degrees C test identifying a successful site were >
      90%. CONCLUSIONS: Low-temperature radiofrequency applications that cause
      transient AP block predict permanent success when a higher-temperature
      application is delivered at the same site. The time to achieve conduction block
      is a function of the temperature set point, and low-temperature tests produce
      reversible conduction block, suggesting minimal permanent injury.

PMID- 8759064
TI  - Angiotensin-converting enzyme inhibition with quinapril improves endothelial
      vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial
      on Reversing ENdothelial Dysfunction) Study.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors may exert some of
      their benefits in the therapy of hypertension, congestive heart failure, and
      acute myocardial infarction by their improvement of endothelial dysfunction.
      TREND (Trial on Reversing ENdothelial Dysfunction) investigated whether quinapril
      might improve endothelial dysfunction in normotensive patients with coronary
      artery disease and no heart failure, cardiomyopathy, or major lipid abnormalities
      so that confounding variables that affect endothelial dysfunction could be
      minimized. METHODS AND RESULTS: Using a double-blind, randomized, placebo
      controlled design, we measured the effects of quinapril (40 mg daily) on coronary
      artery diameter responses to acetylcholine using quantitative coronary
      angiography. The primary response variable was the net change in the
      acetylcholine-provoked constriction of target segments between the baseline
      (prerandomization) and 6-month follow-up angiograms. The constrictive responses
      to acetylcholine were comparable in the placebo (n = 54) and quinapril (n = 51)
      groups at baseline. After 6 months, only the quinapril group showed significant
      net improvement in response to incremental concentrations of acetylcholine (4.5
      +/- 3.0% [mean +/- SEM] versus -0.1 +/- 2.8% at 10(-6) mol/L and 12.1 +/- 3.0%
      versus -0.8 +/- 2.9% at 10(-4) mol/L, quinapril versus placebo, respectively;
      overall P = .002). CONCLUSIONS: TREND shows that ACE inhibition with quinapril
      improved endothelial dysfunction in patients who were normotensive and who did
      not have severe hyperlipidemia or evidence of heart failure. These benefits of
      ACE inhibition are likely due to attenuation of the contractile effects and
      superoxide-generating effects of angiotensin II and to enhancement of endothelial
      cell release of nitric oxide secondary to diminished breakdown of bradykinin.

PMID- 8759065
TI  - Nitric oxide activity is deficient in spasm arteries of patients with coronary
      spastic angina.
AB  - BACKGROUND: Coronary spasm can be induced by acetylcholine, serotonin,
      ergonovine, or histamine, all of which cause vasodilation when the endothelium is
      intact by releasing nitric oxide (NO). Coronary spasm is promptly relieved by
      nitroglycerin, which vasodilates through its conversion to NO. It is thus
      possible that NO release may be deficient in the spasm arteries in patients with
      coronary spastic angina (CSA). The aim of this study was to determine whether NO
      release is deficient in coronary arteries of patients with CSA. METHODS AND
      RESULTS: NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase, was
      infused into coronary arteries in 21 patients with coronary spastic angina (CSA)
      and in 28 control patients. Coronary spasm was induced by intracoronary injection
      of acetylcholine and was documented angiographically in all patients with CSA. L
      NMMA dose-dependently decreased basal luminal diameter of coronary arteries in
      control patients, whereas it had no effect on basal diameter of the spasm
      arteries in patients with CSA. L-NMMA abolished the dilator response to
      acetylcholine and enhanced the constrictor response to acetylcholine in control
      arteries, whereas it had no effect on the constrictor response to acetylcholine
      in spasm arteries. Intracoronary infusion of L-arginine did not affect the
      diameter of spasm or control arteries. The dilator response to nitroglycerin was
      increased markedly in spasm arteries compared with control arteries, whereas
      response to diltiazem did not differ between them. CONCLUSIONS: There is a
      deficiency in endothelial NO activity in spasm arteries, which leads to the
      supersensitivity of the artery to the vasodilator effect of nitroglycerin and to
      the vasoconstrictor effect of acetylcholine in patients with CSA. This deficient
      endothelial NO activity plays an important role in the pathogenesis of coronary
      spasm.

PMID- 8759066
TI  - Apolipoprotein A-I and B levels and the risk of ischemic heart disease during a
      five-year follow-up of men in the Quebec cardiovascular study.
AB  - BACKGROUND: Results obtained largely from case-control studies have suggested
      that an elevated plasma concentration of apolipoprotein (apo) B may be considered
      an important risk factor for ischemic heart disease (IHD). Prospective data on
      the relevance of measuring apo A-I and apo B levels in the assessment of IHD
      risk, however, remain sparse as well as controversial. METHODS AND RESULTS:
      Plasma lipid, apo B, and apo A-I levels as well as other risk factors were
      evaluated at baseline in 1985 in a sample of 2155 men (45 to 76 years old) who
      were followed for a period of 5 years for clinical signs of IHD. Proportional
      hazards analyses indicated that plasma apo B concentrations measured at entry
      were strongly associated with onset of IHD (relative rate, 1.4; 95% confidence
      interval [CI], 1.2 to 1.7), independent of covariables such as age, smoking,
      diabetes mellitus, and systolic blood pressure. Controlling for triglycerides,
      HDL cholesterol, and total/HDL cholesterol ratio did not eliminate the
      relationship between plasma apo B levels and IHD. The association between apo A-I
      and IHD was of lower magnitude (relative rate, 0.85; 95% CI, 0.7 to 1.0), and
      adjustment for selected plasma lipid and lipoprotein levels eliminated this
      association. Stepwise logistic regression analysis revealed that, among metabolic
      variables, apo B was the strongest correlate of IHD. CONCLUSIONS: These
      prospective results emphasize the importance of apo B as a risk factor for IHD.
      Apo B may be regarded as a relevant tool in the assessment of IHD risk in men,
      because it may provide information that would not be obtained from the
      conventional lipid-lipoprotein profile.

PMID- 8759067
TI  - Platelet activation and coronary stent implantation. Effect of antithrombotic
      therapy.
AB  - BACKGROUND: Platelet activation and surface expression of adhesive glycoproteins
      play a key role in ischemic thrombotic complications after coronary intervention.
      The purpose of this case-control study was to evaluate the effects of two
      different antithrombotic regimens on platelet function after coronary Palmaz
      Schatz stent implantation. METHODS AND RESULTS: The study group consisted of 46
      "low-risk" patients who were treated with ticlopidine (250 mg BID) and aspirin
      (100 mg BID) after stenting. The control group was derived from a cohort of 151
      patients receiving conventional anticoagulation therapy, including phenprocoumon
      (target international normalized ratio, 3.5), heparin (activated partial
      thromboplastin time, 80 to 120 seconds), and aspirin (100 mg BID) after stenting.
      Criteria for matching were indication for stenting, target vessel, balloon size,
      inflation pressure, and number of inserted stents. Matches were obtained for 38
      patients. Platelet function was evaluated before and daily for 12 days after
      stenting in venous blood samples with immunologic activation markers. Patients
      receiving anticoagulation therapy showed a significantly increased surface
      exposure of LIBS1 (activated fibrinogen receptor; P < .05) and CD62P (P-selectin;
      P < .001) above prestent values, peaking days 3 to 6 after stenting. In contrast,
      in patients receiving ticlopidine, expression of LIBS1 decreased (P < .01) and
      expression of CD62P remained basically unchanged after stenting. Platelet count
      significantly decreased after stenting in patients treated by anticoagulation
      (day 3; P < .01), whereas no significant changes were found in the ticlopidine
      group. CONCLUSIONS: Significant platelet activation occurs in patients receiving
      anticoagulation therapy after stenting, while platelet deactivation is found in
      patients treated with combined antiplatelet therapy. This may contribute to a
      lowering of the incidence of subacute stent thrombosis.

PMID- 8759068
TI  - Comparison of myocardial perfusion reserve before and after coronary balloon
      predilatation and after stent implantation in patients with postangioplasty
      restenosis.
AB  - BACKGROUND: Stents provide a scaffold for coronary arteries after angioplasty and
      inhibit elastic recoil. METHODS AND RESULTS: In 25 patients with postangioplasty
      restenosis of the left anterior descending artery, ECG-gated digital subtraction
      coronary angiograms were recorded at baseline and during hyperemia (12 mg
      papaverine IC) before and after balloon predilatation (PTCA), after implantation
      of a Palmaz-Schatz stent, and after 6 months. Densitometric evaluation revealed
      different time and density parameters to calculate two definitions of myocardial
      perfusion reserve (MPR1 and MPR2) and maximum flow ratio (MaxFR). Poststenotic
      MPR1 increased from 1.57 +/- 0.14 to 2.59 +/- 0.86 after PTCA and to 3.10 +/-
      0.41 after stenting, with 2.90 +/- 0.65 at follow-up (ANOVA, P < .05), while
      reference MPR1 remained unchanged at 3.10 +/- 0.40. Poststenotic MPR2 increased
      from 1.36 +/- 0.28 to 2.50 +/- 1.20 and to 3.40 +/- 0.58, respectively, with 3.20
      +/- 0.92 at follow-up (ANOVA, P < .05), while reference MPR2 remained unchanged
      at 3.40 +/- 0.60. MaxFR was 2.13 +/- 0.53 after PTCA, elasticity 2.83 +/- 0.35
      after stenting, and 2.73 +/- 0.58 at follow-up (ANOVA, P < .05). A good
      correlation was found between minimal stenotic luminal diameter and MPR1 or MPR2
      (r = .87 and r = .94) and between luminal gain and MaxFR (r = .75). A negative
      correlation was measured between recoil and MPR1, MPR2, and MaxFR (r = -.80, r = 
      .86, and r = -.83). At follow-up, a steeper correlation was found between MPR and
      minimal stenosis diameter (MPR1: slope, 0.52 versus 0.91; MPR2: slope, 1.48
      versus 1.95) and between MaxFR and net lumen gain (slope, 0.78 versus 1.27).
      CONCLUSIONS: Coronary stent implantation in patients with postangioplasty
      restenosis normalized poststenotic myocardial perfusion immediately as a result
      of a larger postprocedural lumen and a more pronounced inhibition of elastic
      recoil. After 6 months this benefit was sustained despite progressive lumen loss.

PMID- 8759069
TI  - Beneficial effects of RheothRx injection in patients receiving thrombolytic
      therapy for acute myocardial infarction. Results of a randomized, double-blind,
      placebo-controlled trial.
AB  - BACKGROUND: RheothRx (poloxamer 188) is a surfactant with hemorheological and
      antithrombotic properties that reduces myocardial reperfusion injury in animal
      models of myocardial infarction. The purpose of the present study was to evaluate
      the safety and efficacy of adjunctive therapy with poloxamer 188 in patients
      receiving thrombolytic therapy for acute myocardial infarction. METHODS AND
      RESULTS: In this multicenter trial, we randomized 114 patients to a 48-hour
      infusion of poloxamer 188 or vehicle placebo beginning immediately after the
      initiation of thrombolytic therapy. Tomographic imaging with 99mTc sestamibi
      before reperfusion and again 5 to 7 days after the infarction was used to
      determine myocardium at risk for infarction, infarct size, and myocardial
      salvage. Radionuclide angiography at 5 to 7 days after infarction was used to
      measure left ventricular ejection fraction. The treated and control groups had
      comparable baseline characteristics, time to thrombolytic administration, and
      time to treatment with poloxamer 188 or placebo. Poloxamer 188-treated patients
      demonstrated a 38% reduction in median myocardial infarct size (25th and 75th
      percentile) compared with placebo (16% [7, 30] versus 26% [9, 43]; P = .031),
      greater median myocardial salvage (13% [7, 20] versus 4% [1, 15]; P = .033), and
      a 13% relative improvement in median ejection fraction (52% [43, 60] versus 46%
      [35, 60]; P = .020). Poloxamer 188 treatment also resulted in a reduced incidence
      of reinfarction (1% versus 13%; P = .016). Poloxamer 188 was well tolerated
      without adverse hemodynamic effects or significant organ toxicity. CONCLUSIONS:
      Adjunctive therapy with poloxamer 188 resulted in substantial benefit in this
      randomized trial, including significantly smaller infarcts, greater myocardial
      salvage, better left ventricular function, and a lower incidence of in-hospital
      reinfarction. Although the mechanisms are unproven, poloxamer 188 treatment may
      accelerate thrombolysis, reduce reocclusion, and ameliorate reperfusion injury.

PMID- 8759070
TI  - Only hibernating myocardium invariably shows early recovery after coronary
      revascularization.
AB  - BACKGROUND: The aims of this study were to identify hibernating myocardium
      (hypocontractile, hypoperfused viable myocardium that regains contractility after
      revascularization) in the clinical setting and to predict functional outcome in
      patients with coronary artery disease after coronary revascularization. METHODS
      AND RESULTS: Preoperative data related to the anterior free wall of the left
      ventricle were collected in 50 coronary bypass surgery candidates (positron
      emission tomography [PET], [13N]NH3 for flow, and [18F]FDG for metabolism [MET];
      equilibrium-gated nuclear angiography [EGNA] for regional ejection fraction
      [REF]; and histological data from myocardial biopsies for percentage fibrosis and
      viable myocytes). Three months after surgery, the patients had follow-up PET and
      EGNA investigations. A principal-components analysis identified four patient
      clusters. Cluster 1 (n = 9) had normal viable myocardium. Cluster 2 (n = 18) had
      viable hypocontractile myocardium (REF, 39 +/- 12%) showing a PET mismatch
      pattern. Cluster 3 (n = 16) had viable hypocontractile myocardium associated with
      morphological myocyte injury showing a matched moderate decrease in flow (66 +/-
      11%) and MET (70 +/- 11%). Cluster 4 (n = 7) had hypocontractile myocardium with
      mainly scar tissue (fibrosis, 74 +/- 12%). After surgery, only cluster 2, with
      hibernating myocardium, showed significant improvement in REF (from 39 +/- 12% to
      50 +/- 13%, P < .05). Cluster 3, with sites of morphological myocyte injury,
      showed no recovery. The stepwise logistic regression showed a combination of low
      preoperative REF and high MET to be the best predictor of functional recovery (P
      < .008). CONCLUSIONS: Multivariate analysis identifies hibernating myocardium
      showing early postrevascularization recovery, as opposed to viable but myolytic
      myocardium with no early recovery. Postrevascularization recovery can be
      predicted (combination of low REF and high MET) by noninvasive techniques.

PMID- 8759071
TI  - Endothelin and calcium antagonists in the skin microcirculation of patients with
      coronary artery disease.
AB  - BACKGROUND: Endothelin, a potent endothelium-derived vasoconstrictor peptide, is
      elevated in coronary artery disease (CAD); however, its pathophysiological role
      is uncertain. Calcium antagonists are widely used in patients with CAD. Using
      laser Doppler flowmetry, we investigated the influence of two endothelin
      antagonists and the calcium antagonist diltiazem on endogenous and exogenous
      endothelin in the skin microcirculation of CAD patients and healthy control
      subjects. METHODS AND RESULTS: Both endothelin antagonists and diltiazem applied
      intradermally induced vasodilation in CAD patients, which was more pronounced
      with the ETA/ETB antagonist than with the ETA antagonist or diltiazem. Exogenous
      endothelin led to profound vasoconstriction in CAD patients and healthy
      volunteers. Both endothelin antagonists and diltiazem blunted the
      vasoconstriction to exogenous endothelin in CAD patients and young healthy
      volunteers and less so in old healthy volunteers. However, compared with both
      endothelin antagonists, a 10-times-higher dose of diltiazem was required.
      Systemic diltiazem (240 mg, slow release) attenuated endothelin-induced
      vasoconstriction in CAD patients. Neurogenic vasodilation to exogenous endothelin
      was inhibited by both endothelin antagonists. CONCLUSIONS: This study
      demonstrates that endogenous endothelin of CAD patients contributes to the
      regulation of vascular tone in the skin microcirculation not only through ETA
      receptors but also possibly through ETB receptors. Diltiazem inhibited endothelin
      induced vasoconstriction, but endothelin antagonists were slightly more
      effective. Thus, endothelin antagonists represent potent new tools to interfere
      with the vascular effects of endothelin in CAD patients. Future studies must
      confirm these findings in other areas of the circulation.

PMID- 8759072
TI  - Skeletal muscle and cardiovascular adaptations to exercise conditioning in older
      coronary patients.
AB  - BACKGROUND: Older coronary patients suffer from a low functional capacity and
      high rates of disability. Supervised exercise programs improve aerobic capacity
      in middle-aged coronary patients by improving both cardiac output and peripheral
      extraction of oxygen. Physiological adaptations to aerobic conditioning, however,
      have not been well studied in older coronary patients. METHODS AND RESULTS: The
      effect of a 3-month and a 1-year program of intense aerobic exercise was studied
      in 60 older coronary patients (mean age, 68 +/- 5 years) beginning 8 +/- 5 weeks
      after myocardial infarction or coronary bypass surgery. Outcome measures included
      peak aerobic capacity, cardiac output, arterio-venous oxygen difference,
      hyperemic calf blood flow, and skeletal muscle fiber morphometry, oxidative
      enzyme activity, and capillarity. Training results were compared with a
      sedentary, age- and diagnosis-matched control group (n = 10). Peak aerobic
      capacity increased in the intervention group at 3 months and at 1 year by 16% and
      20%, respectively (both P < .01). Peak exercise cardiac output, hyperemic calf
      blood flow, and vascular conductance were unaffected by the conditioning
      protocol. At 3 and 12 months, arteriovenous oxygen difference at peak exercise
      was increased in the exercise group but not in control subjects. Histochemical
      analysis of skeletal muscle documented a 34% increase in capillary density and a
      23% increase in succinate dehydrogenase activity after 3 months of conditioning
      (both P < .02). At 12 months, individual fiber area increased by 29% compared
      with baseline (P < .01). CONCLUSIONS: Older coronary patients successfully
      improve peak aerobic capacity after 3 and 12 months of supervised aerobic
      conditioning compared with control subjects. The mechanism of the increase in
      peak aerobic capacity is associated almost exclusively with peripheral skeletal
      muscle adaptations, with no discernible improvements in cardiac output or calf
      blood flow.

PMID- 8759073
TI  - Determinants of increased regional left atrial coagulation activity in patients
      with mitral stenosis.
AB  - BACKGROUND: Recent evidence suggests that regional left atrial coagulation
      activity may be increased in mitral stenosis and perhaps contribute to the
      pathophysiology of left atrial thrombus. However, the relation of left atrial
      coagulation activity to factors that predispose to left atrial thrombus formation
      is unknown, and the relation between left atrial and systemic coagulation
      activities is unresolved. METHODS AND RESULTS: Left atrial and peripheral venous
      levels of the coagulation marker prothrombin fragment 1 + 2 (F1 + 2) were
      measured in 32 patients with mitral stenosis with normal clotting times and no
      left atrial thrombus who were undergoing percutaneous balloon mitral
      valvuloplasty. Baseline peripheral venous F1 + 2 levels, measured at the
      beginning of the valvuloplasty procedure, did not differ from those of 30 age
      matched control patients. Prevalvuloplasty left atrial F1 + 2 levels, obtained
      immediately after transseptal puncture, were similar to femoral venous levels in
      patients without left atrial spontaneous echo contrast (LASEC) (0.81 +/- 0.32
      versus 0.81 +/- 0.27 nmol/L, n = 7) but greater than femoral venous levels in
      patients with LASEC and either sinus rhythm (1.57 +/- 0.86 versus 0.99 +/- 0.38
      nmol/L, n = 16, P < .001) or atrial fibrillation (1.52 +/- 0.69 versus 0.85 +/-
      0.33 nmol/L, n = 9, P < .003). Furthermore, LASEC emerged as the only significant
      predictor of increased regional left atrial coagulation activity (P = .005) on
      stepwise multivariate logistic regression analysis. CONCLUSIONS: Increased
      regional left atrial coagulation activity in mitral stenosis occurs in the
      presence of LASEC, is evident in either sinus rhythm or atrial fibrillation, and
      is associated with normal systemic coagulation activity.

PMID- 8759074
TI  - Negative chronotropic effect of beta-blockade therapy reduces myocardial oxygen
      expenditure for nonmechanical work.
AB  - BACKGROUND: The negative chronotropic effect of beta-blocking agents is likely to
      provide hemodynamic and energetic advantages. However, the negative chronotropic
      effect on cardiac energetics observed on the initiation of beta-blockade therapy
      has not been fully elucidated. METHODS AND RESULTS: In 18 patients with heart
      failure, left ventricular pressure and volume, external work (EW), myocardial
      oxygen consumption per beat (total Vo2), mechanical efficiency (EW/total Vo2),
      and Vo2 for nonmechanical work (total Vo2-2.EW) were measured with the use of
      conductance catheter and Webster catheter at the following three states: under
      control conditions and after beta-blockade (0.15 +/- 0.07 mg/kg propranolol IV)
      with and without atrial pacing to keep the heart rate at control levels. Heart
      rate decreased after atrial pacing was stopped. EW decreased during beta-blockade
      with pacing and returned to the control level after pacing was stopped. Total Vo2
      did not change during beta-blockade with or without pacing, whereas Vo2 for
      nonmechanical work increased with pacing and returned to the control level after
      pacing was stopped. As a result, mechanical efficiency decreased during beta
      blockade with pacing and returned to the control level after pacing was stopped.
      CONCLUSIONS: The negative chronotropic effect of a beta-blocking agent may offset
      the mechanoenergetical deterioration resulting from its negative inotropic effect
      through a reduction in oxygen expenditure for nonmechanical work. These findings
      suggest that the negative chronotropic effect is an important aspect of beta
      blockade therapy.

PMID- 8759075
TI  - Diltiazem improves cardiac function and exercise capacity in patients with
      idiopathic dilated cardiomyopathy. Results of the Diltiazem in Dilated
      Cardiomyopathy Trial.
AB  - BACKGROUND: Evidence is arising that calcium antagonists in idiopathic dilated
      cardiomyopathy (IDC) may have beneficial effects on virus-induced
      cardiopathology, alcohol toxicity, micro-circulatory disorders, and impaired
      calcium cycling, all possibly involved in the pathogenesis of the disease. Thus,
      the effect of adjunct diltiazem (60 to 90 mg TID) on standard treatment was
      investigated. METHODS AND RESULTS: The Diltiazem in Dilated Cardiomyopathy (DiDi)
      trial was a randomized, double-blind, placebo-controlled, multicenter trial of
      186 patients (92 receiving diltiazem, 94 receiving placebo) with IDC diagnosed by
      coronary angiography, catheterization of the left side of the heart, and a left
      ventricular ejection fraction of < 0.50 (mean, 0.34 +/- 0.11). The effect of
      adjunct diltiazem treatment on transplant listing-free survival, hemodynamics,
      exercise capacity, and subjective status was investigated. During the 24-month
      study period, 33 patients dropped out of the study; 153 patients finished the
      study protocol. Twenty-seven patients died or had a listing for heart
      transplantation: 16 in the placebo group and 11 in the diltiazem group. The
      transplant listing-free survival rate was 85% for diltiazem and 80% for placebo
      recipients (P = .444). After 24 months, only diltiazem significantly increased
      cardiac index at rest (P = .01) and under a workload (P = .02), systolic and
      diastolic pressures (P = .003 and P = .004), stroke volume index (P = .003), and
      stroke work index (P = .000) and decreased both pulmonary artery pressure under
      workload (P = .007) and heart rate (P = .001). Diltiazem also increased exercise
      capacity (P = .002) and subjective well-being (P = .01). Adverse reactions were
      minor and evenly distributed in both groups, except for an increase in the PQ
      interval in the diltiazem group. CONCLUSIONS: In patients with IDC, the adjunct
      therapy of diltiazem improves cardiac function, exercise capacity, and subjective
      status without deleterious effects on transplant listing-free survival.

PMID- 8759076
TI  - Acute effects of beta 1-selective and nonselective beta-adrenergic receptor
      blockade on cardiac sympathetic activity in congestive heart failure.
AB  - BACKGROUND: beta-Blockers may reduce cardiac sympathetic activity in patients
      with heart failure by antagonizing beta-adrenergic receptors that facilitate
      sympathetic outflow to the heart. To explore this possible effect of beta
      blockade, we measured cardiac norepinephrine spillover responses in patients with
      heart failure after the acute administration of either propranolol, a
      nonselective beta-blocker, or metoprolol, a beta 1-selective agent. METHODS AND
      RESULTS: Eighteen patients were studied. Repeated intravenous doses of
      propranolol (0.5 mg; nine patients; left ventricular ejection fraction, 14 +/-
      2%) or metoprolol (1.0 mg; nine patients; left ventricular ejection fraction, 18
      +/- 2%) were administered until one of the following end points was reached: a
      15% decrease in heart rate, left ventricular +dP/dt, or mean arterial blood
      pressure or a 5 mm Hg increase in left ventricular end-diastolic pressure.
      Propranolol (mean dose, 2.0 mg) and metoprolol (mean dose, 3.6 mg) caused similar
      reductions in heart rate, +dP/dt, and coronary sinus plasma flow. Cardiac
      norepinephrine spillover was reduced after propranolol (277 +/- 55 to 262 +/- 53
      pmol/min, P < .05) but was increased after metoprolol (233 +/- 57 to 296 +/- 82
      pmol/min, P < .05). In a comparison of the two groups, the decrease in spillover
      after propranolol was significantly different than the increase seen after
      metoprolol (P < .01). CONCLUSIONS: The administration of a beta 1-selective
      antagonist was associated with increased cardiac norepinephrine spillover. In
      contrast, the administration of a nonselective beta-blocker until similar
      hemodynamic end points were reached caused a reduction in norepinephrine
      spillover. This suggests that in patients with heart failure, nonselective beta
      blockade may have favorable inhibitory effects on cardiac sympathetic activity.

PMID- 8759077
TI  - Continuum of cardiovascular performance across a broad range of fitness levels in
      healthy older men.
AB  - BACKGROUND: Although it has become clear that habitual exercise in older
      individuals can partially offset age-associated cardiovascular declines, it is
      not known whether the beneficial effects of exercise training in older
      individuals depend on their prior fitness level. METHODS AND RESULTS: Ten
      sedentary men (S), age 60.0 +/- 1.6 years (mean +/- SEM), who were carefully
      screened to exclude cardiac disease underwent exercise training for 24 to 32
      weeks, and eight age-matched endurance-trained men (ET) stopped their exercise
      training for 12 weeks. All underwent treadmill exercise and rest and maximal
      cycle exercise upright gated blood pool scans at baseline and after the lifestyle
      intervention. Before the intervention, the treadmill maximum rate of oxygen
      consumption (Vo2max) was 49.9 +/- 1.9 and 32.1 +/- 1.4 mL.kg-1.min-1 in ET and S,
      respectively. During upright cycle exercise at exhaustion, although heart rate
      did not differ between groups, cardiac index, stroke volume index, ejection
      fraction, and left ventricular contractility index (systolic blood pressure/end
      systolic volume index) all were significantly higher, and end-systolic volume
      index, diastolic blood pressure, and total systemic vascular resistance all were
      significantly lower in ET versus S. After the partial deconditioning of ET men,
      Vo2max fell to 42 +/- 2.2 mL.kg-1.min-1, and training of S increased Vo2max to
      36.2 +/- 1.6 mL.kg-1.min-1. Training of S had effects on cardiovascular function
      that were similar in magnitude but directionally opposite those of detraining ET.
      All initial differences in cardiovascular performance at peak work rate between S
      and ET were abolished with the intervention. Across the broad range of fitness
      levels encountered before and after change in training status (Vo2max of 26 to 58
      mL.kg-1.min-1), cardiac index, stroke volume index, end-systolic volume index,
      ejection fraction, and the left ventricular contractility index were all linearly
      correlated with Vo2max. CONCLUSIONS: Exercise training or detraining of older men
      results in changes in left ventricular performance that are qualitatively and
      quantitatively similar, regardless of the initial level of fitness before the
      intervention.

PMID- 8759078
TI  - Innervation of human atrioventricular and arterial valves.
AB  - BACKGROUND: Limited information exists on the innervation of human cardiac valves
      and the relationship of nerve fibers and terminals with functional elements
      within leaflets. METHODS AND RESULTS: We examined human AV and arterial valves,
      obtained postmortem and at surgery, using quantitative immunohistochemical,
      histochemical, and confocal microscopic techniques. Significant differences in
      nerve density and distribution were found both between and within cardiac valves.
      Nerve density within the anterior leaflet of the mitral valve, for example, was
      twofold greater than that in the posterior leaflet (P < .001). Nerves within the
      AV valves were situated in the atrial layer and extended over the proximal and
      medial portions of the leaflets, whereas those in the arterial valves were
      situated in the ventricular layer. No nerves reached either the free edge or the
      fibrous core of the leaflets. The arterial valves displayed a similar density of
      innervation, except for the noncoronary leaflet of the aortic valve in which the
      innervation was attenuated (P < .01). The innervation of aortic valvar leaflets
      was age dependent. Nerve terminal arborizations, arising from myelinated nerves
      and exhibiting variable morphology, were detected in all four cardiac valves and
      in some tendinous cords. Nerve terminals exhibited either acetylcholinesterase
      activity or tyrosine hydroxylase and neuropeptide Y immunoreactivity. Varicose
      nerve fibers occurred in close physical proximity to valvar endothelial, smooth
      muscle, and fibroblast cells. CONCLUSIONS: Human cardiac valves have distinct
      patterns of innervation that comprise both primary sensory and autonomic
      components. The presence of distinct nerve terminals and the close association of
      varicose nerve fibers with endothelial, smooth muscle, and fibroblast cells
      suggest a possible neural involvement in the control of valvar function.

PMID- 8759079
TI  - Radiofrequency current catheter ablation of accessory atrioventricular pathways
      in Ebstein's anomaly.
AB  - BACKGROUND: In patients with Ebstein's anomaly, localization of accessory
      pathways (APs) may be impeded by abnormal local electrograms recorded along the
      atrialized right ventricle and by the presence of multiple APs. The impact of
      these factors on radiofrequency (RF) current catheter ablation of APs has not
      been evaluated yet. METHODS AND RESULTS: Twenty-one patients with Ebstein's
      anomaly and reentrant atrioventricular tachycardias underwent
      electrophysiological evaluation and subsequent attempts at RF catheter ablation.
      Thirty-four right-sided APs were found, with 30 located along the atrialized
      ventricle. Local electrograms in this region were normal in 10 patients but
      fragmented in 11. Fragmented electrograms prevented the clear distinction between
      atrial and ventricular activation potentials as well as the identification of AP
      potentials. Right coronary artery mapping was performed in 7 patients. Abolition
      of all 26 APs was achieved in the 10 patients with normal local electrograms and
      in 6 of 11 patients with abnormal electrograms. Right coronary artery mapping
      allowed AP localization and ablation in 5 patients. In the 5 patients with
      abnormal electrograms and a total of 8 APs, 6 APs could not be ablated.
      Unsuccessfully treated patients received antiarrhythmic drugs. During 22 +/- 12
      months of follow-up, 5 patients had clinical recurrences, including 4 who had
      undergone a successful RF procedure. CONCLUSIONS: In patients with Ebstein's
      anomaly and reentrant atrioventricular tachycardias, factors likely to account
      for failure of RF catheter ablation include an AP located along the atrialized
      right ventricle and the abnormal morphology of endocardial activation potentials
      generated in this region.

PMID- 8759080
TI  - Site-dependent intra-atrial conduction delay. Relationship to initiation of
      atrial fibrillation.
AB  - BACKGROUND: Atrial dysrhythmia patients have exaggerated intra-atrial conduction
      delays and prolonged relative refractoriness in response to atrial premature
      depolarizations (APDs). Furthermore, atrial fibrillation (AF) is more readily
      inducible by APDs from the high right atrium (HRA) than the coronary sinus (CS).
      In this study, we postulated that site-specific intra-atrial conduction delays
      can explain why AF is initiated more from the HRA than from the CS. METHODS AND
      RESULTS: We examined 17 patients (age, 49 +/- 22 years) without a history of
      atrial flutter, AF, or structural heart disease. Programmed stimulation was
      carried out from the HRA and distal CS, and bipolar recordings were made at the
      HRA, His bundle, posterior triangle of Koch, and CS. More prolongations in
      conduction and relative refractoriness in all intra-atrial sites were observed
      during HRA than CS APDs. AF was induced in 8 patients after HRA and not CS
      stimulation. During HRA stimulation, patients with AF inducibility exhibited
      significant prolongation of conduction to the posterior triangle of Koch and
      marked broadening of the posterior triangle of Koch electrogram compared with CS
      stimulation. In patients without AF inducibility, the posterior triangle of Koch
      electrogram width was the same during HRA and CS stimulation. CONCLUSIONS: The
      existence of site-dependent intra-atrial conduction delays and site-dependent
      dispersion of refractoriness appears to be a common property of the atrial
      myocardium and does not necessarily forecast AF inducibility. However, the
      presence of nonuniform anisotropic characteristics of the posterior triangle of
      Koch may be critical for AF induction.

PMID- 8759081
TI  - Predictors of atrial fibrillation after coronary artery surgery. Current trends
      and impact on hospital resources.
AB  - BACKGROUND: Atrial fibrillation (AF) after coronary artery bypass surgery (CABG)
      is the most common sustained arrhythmia. Its pathophysiology is unclear, and its
      prevention and management remain suboptimal. The aim of this prospective study
      was to determine the current incidence of AF, identify its clinical predictors,
      and examine its impact on resource utilization. METHODS AND RESULTS: Over a 12
      month period ending July 31, 1994, a CABG procedure was performed on 570
      consecutive patients (age range, 32 to 87 years; median age, 67 years; 232 [41%]
      were > or = 70 years; 175 [31%] were women; 173 [30%] were diabetics; 364 [65%]
      required nonelective surgery; 86 [15%] had had a prior CABG; and 86 [15%] had had
      prior percutaneous transluminal coronary angioplasty). AF occurred in 189
      patients (33%). The median age for patients with AF was 71 years compared with 66
      for patients without (P = .0001). Multivariate logistic regression analysis (odds
      ratio, +/- 95% CI, P value) was used to identify the following independent
      predictors of postoperative AF: increasing age (age 70 to 80 years [OR = 2; CI,
      1.3 to 3; P = .002], age > 80 years [OR = 3; CI, 1.6 to 5.8; P = .0007]), male
      gender (OR = 1.7; CI, 1.1 to 2.7; P = .01), hypertension (OR = 1.6; CI, 1.0 to
      2.3; P = .03), need for an intraoperative intraaortic balloon pump (OR = 3.5; CI,
      1.2 to 10.9; P = .03), postoperative pneumonia (OR = 3.9; CI, 1.3 to 11.5; P =
      .01), ventilation for > 24 hours (OR = 2; CI, 1.3 to 3.2; P = .003), and return
      to the intensive care unit (OR = 3.2; CI, 1.1 to 8.8; P = .03). The mean length
      of hospital stay after surgery was 15.3 +/- 28.6 days for patients with AF
      compared with 9.3 +/- 19.6 days for patients without AF (P = .001). The adjusted
      length of hospital stay attributable to AF was 4.9 days, corresponding to > or =
      $10 055 in hospital charges. CONCLUSIONS: AF remains the most common complication
      after CABG and consequently is a drain on hospital resources. Concerted efforts
      to reduce the incidence of AF and the associated increased length of stay would
      result in substantial cost saving and decrease patient morbidity.

PMID- 8759082
TI  - Activation and entrainment mapping defines the tricuspid annulus as the anterior
      barrier in typical atrial flutter.
AB  - BACKGROUND: The importance of anatomic barriers in the atrial flutter reentry
      circuit has been well demonstrated in canine models. It has been shown previously
      that the crista terminalis and its continuation as the eustachian ridge form a
      posterior barrier. In this study we tested the hypothesis that the tricuspid
      annulus forms the continuous anterior barrier to the flutter circuit. METHODS AND
      RESULTS: Thirteen patients with typical atrial flutter were studied. A 20-pole
      halo catheter was situated around the tricuspid annulus. A mapping catheter was
      used for activation and entrainment mapping from seven sequential sites around
      the tricuspid annulus and from three additional sites including the tip of the
      right atrial appendage, at the fossa ovalis, and in the distal coronary sinus.
      Sites were considered to be within the circuit when the postpacing interval minus
      the flutter cycle length and the stimulus time minus the activation time were <
      or = 10 ms; sites were considered to be outside the circuit when these intervals
      were > 10 ms. All seven annular sites were within the circuit; activation
      occurred sequentially around the annulus and accounted for 100% of the flutter
      cycle length. The fossa ovalis, the distal coronary sinus, and the right atrial
      appendage were outside the circuit. CONCLUSIONS: Closely spaced sites around the
      tricuspid annulus are activated sequentially, and are all within the flutter
      circuit according to entrainment criteria. This demonstrates that the tricuspid
      annulus constitutes a continuous anterior barrier constraining the reentrant wave
      front of human counterclockwise atrial flutter.

PMID- 8759083
TI  - Role of the tricuspid annulus and the eustachian valve/ridge on atrial flutter.
      Relevance to catheter ablation of the septal isthmus and a new technique for
      rapid identification of ablation success.
AB  - BACKGROUND: Typical atrial flutter (AFL) results from right atrial reentry by
      propagation through an isthmus between the inferior vena cava (IVC) and tricuspid
      annulus (TA). We postulated that the eustachian valve and ridge (EVR) forms a
      line of conduction block between the IVC and coronary sinus (CS) ostium and forms
      a second isthmus (septal isthmus) between the TA and CS ostium. METHODS AND
      RESULTS: Endocardial mapping in 30 patients with AFL demonstrated atrial
      activation around the TA in the counter-clockwise direction (left anterior
      oblique projection). Double atrial potentials were recorded along the EVR in all
      patients during AFL. Pacing either side of the EVR during sinus rhythm also
      produced double potentials, which indicated fixed anatomic block across EVR.
      Entrainment pacing at the septal isthmus and multiple sites around the TA
      produced a delta return interval < or = 8 ms in 14 of 15 patients tested.
      Catheter ablation eliminated AFL in all patients by ablation of the septal
      isthmus in 26 patients and the posterior isthmus in 4. AFL recurred in 2 of 12
      patients (mean follow-up, 33.9 +/- 16.3 months) in whom ablation success was
      defined by the inability to reinduce AFL, compared with none of 18 patients (mean
      follow-up, 10.3 +/- 8.3 months) in whom success required formation of a complete
      line of conduction block between the TA and the EVR, identified by CS pacing that
      produced atrial activation around the TA only in the counterclockwise direction
      and by pacing the posterior TA with only clockwise atrial activation.
      CONCLUSIONS: (1) The EVR forms a line of fixed conduction block between the IVC
      and the CS; (2) the EVR and the TA provide boundaries for the AFL reentrant
      circuit; and (3) verification of a complete line of block between the TA and the
      EVR is a more reliable criterion for long-term ablation success.

PMID- 8759085
TI  - Prognostic significance of heart rate variability in post-myocardial infarction
      patients in the fibrinolytic era. The GISSI-2 results. Gruppo Italiano per lo
      Studio della Sopravvivenza nell' Infarto Miocardico.
AB  - BACKGROUND: Studies performed before the introduction of fibrinolysis showed that
      a low heart rate variability (HRV) is associated with higher mortality in post
      myocardial infarction (MI) patients. We evaluated whether HRV adds information
      relevant to risk stratification in patients treated with fibrinolysis as well.
      METHODS AND RESULTS: From 24-hour ECG recordings obtained at discharge in
      patients treated with recombinant tissue-type plasminogen activator or
      streptokinase, we measured several time-domain indexes of HRV: standard deviation
      (SDNN), root-mean-square of successive differences (RMSSD), and number of RR
      interval increases > 50 ms ("NN50+"). The prognostic value of HRV for total and
      cardiovascular mortality was assessed. Of 567 patients with valid recordings, 52
      (9.1%) died during the 1000 days of follow-up, 44 (7.8%) of cardiovascular
      causes. All indexes of low HRV were able to identify patients (16% to 18% of
      total population) with a higher total mortality (20.8% to 24.2% versus 6.0% to
      6.8%, depending on index used). The independent predictive value of low HRV was
      confirmed by the adjusted analysis with the following relative risks: NN50+, 3.5
      (95% CI, 1.9 to 6.7); SDNN, 3.0 (95% CI, 1.55 to 5.9); and RMSSD, 2.8 (95% CI,
      1.5 to 5.3). Advanced age, previous MI, Killip class at entry, and use of
      digitalis were also independent predictors. Similar data were obtained for
      cardiovascular mortality. CONCLUSIONS: Time-domain indexes of HRV retain their
      independent prognostic significance even in post-MI patients of all ages treated
      with fibrinolysis.

PMID- 8759084
TI  - Fibrin D-dimer and beta-thromboglobulin as markers of thrombogenesis and platelet
      activation in atrial fibrillation. Effects of introducing ultra-low-dose warfarin
      and aspirin.
AB  - BACKGROUND: Previous studies have demonstrated increased markers of
      thrombogenesis in patients with atrial fibrillation (AF), suggesting the presence
      of a hypercoagulable or prothrombotic state. The objective of this study was to
      determine the effects of introducing ultra-low-dose warfarin (1 mg), conventional
      warfarin, and aspirin. (300 mg) therapy on thrombogenesis and platelet activation
      in AF. METHODS AND RESULTS: We measured sequential changes in plasma fibrin D
      dimer (an index of thrombogenesis) and beta-thromboglobulin (beta-TG, a measure
      of platelet activation) in 51 patients with chronic AF before and at 2 and 6
      weeks after randomization to either 1 mg warfarin or 300 mg aspirin (phase 1).
      Then all patients were started on conventional warfarin therapy (phase 2) with
      samples taken 2 and 6 weeks later. Pretreatment results were compared with those
      from 26 healthy control subjects in sinus rhythm. Baseline (pretreatment) beta-TG
      and D-dimer levels in patients with AF were elevated compared with those of
      control subjects (P < .001). In phase 1, there were no significant changes in
      median levels of fibrin D-dimer or beta-TG, despite warfarin 1 mg or aspirin 300
      mg. With standard warfarin therapy (phase 2), there was a reduction in median
      beta-TG at 6 weeks (P = .025) and a sequential reduction in median D-dimer levels
      at 2 (P = .001) and 6 (P < .001) weeks compared with baseline levels.
      CONCLUSIONS: Patients with AF have increased intravascular thrombogenesis and
      platelet activation compared with patients in sinus rhythm. Introduction of ultra
      low-dose warfarin (1 mg) or aspirin 300 mg does not significantly alter these
      markers, although conventional warfarin therapy reduces beta-TG and fibrin D
      dimer levels. This is consistent with the beneficial effect of full-dose warfarin
      in preventing stroke and thromboembolism in AF and suggests that ultra-low-dose
      warfarin and aspirin may not exert similar beneficial effects.

PMID- 8759086
TI  - Usefulness of electron-beam computed tomography in arrhythmogenic right
      ventricular dysplasia. Relationship to electrophysiological abnormalities and
      left ventricular involvement.
AB  - BACKGROUND: Electron-beam computed tomography (CT) may be useful for detecting
      myocardial fat infiltration and diagnosing arrhythmogenic right ventricular
      dysplasia (ARVD). There are several characteristic electron-beam CT findings of
      ARVD. However, the incidence, their relation to electrophysiological
      abnormalities, and the usefulness of electron-beam CT for evaluating left
      ventricular involvement are unknown. This study aimed to clarify these issues.
      METHODS AND RESULTS: Electron-beam CT was performed in 14 patients with ARVD
      (ARVD group), 16 age- and sex-matched patients with right ventricular enlargement
      and/or dysfunction without ARVD (RV enlargement group), and 13 control subjects
      (control group). The incidences of abnormal electron-beam CT findings in the
      three groups were examined. Furthermore, we examined the endocardial fat
      infiltrated areas detected by electron-beam CT (CT-A) and electrophysiologically
      abnormal areas detected in the mapping electrophysiology study (EPS-A) and
      compared the relationship between them in the ARVD group. (1) The frequencies of
      abundant epicardial adipose tissue, low-attenuation trabeculations, scalloping of
      the right ventricular free wall, and intramyocardial fat deposits were 86%, 71%,
      79%, and 50%, respectively, in the ARVD group, whereas these findings were not
      observed in the RV enlargement and control groups. (2) Three ARVD patients (21%)
      had adipose tissue involvement of the left ventricle. (3) The relationship
      between CT-A and EPS-A was as follows: CT-A > EPS-A, 71%; CT-A = EPS-A, 14%; and
      EPS-A only, 14%. CONCLUSIONS: Characteristic electron-beam CT findings are
      frequently observed only in patients with ARVD. Electron-beam CT is useful for
      evaluating for left ventricular involvement and can estimate EPS-A.

PMID- 8759087
TI  - Relation between air-filled albumin microbubble and red blood cell rheology in
      the human myocardium. Influence of echocardiographic systems and chest wall
      attenuation.
AB  - BACKGROUND: We have previously shown that the intravascular rheology of sonicated
      air-filled albumin microbubbles is similar to that of red blood cells (RBCs) and
      that their myocardial transit rate is also similar to that of RBCs in the beating
      canine heart. In the present study, we tested the hypothesis that the myocardial
      transit rates of these microbubbles reflect those of RBCs in humans at different
      coronary flow rates. METHODS AND RESULTS: RBC and microbubble transit rates were
      measured in 17 patients undergoing coronary angiography: in 8, measurements were
      made only at rest, whereas in 9, they were performed both at rest and during a
      pacing-induced increase in coronary blood flow. A gamma-variate function was used
      to derive mean RBC and microbubble transit rates from the time-activity and time
      intensity plots after the left main injection of RBCs and microbubbles,
      respectively. There was linear correlation between the myocardial transit rates
      with both tracers with the slope of the correlation determined by the specific
      echocardiographic system that was used. Microbubble transit rate consistently
      overestimated RBC transit rate due to artificial narrowing of the time-intensity
      curves caused by chest wall attenuation of the echocardiographic signal, which
      was confirmed through in vitro experiments. CONCLUSIONS: There is close
      correlation between air-filled albumin microbubbles and RBC rheology in the human
      myocardium. The use of these microbubbles in the cardiac catheterization
      laboratory could, therefore, provide further insights into myocardial blood
      flow/myocardial blood volume relations in humans.

PMID- 8759088
TI  - Insights from three-dimensional echocardiographic laser stereolithography. Effect
      of leaflet funnel geometry on the coefficient of orifice contraction, pressure
      loss, and the Gorlin formula in mitral stenosis.
AB  - BACKGROUND: Three-dimensional echocardiography can allow us to address uniquely
      three-dimensional scientific questions, for example, the hypothesis that the
      impact of a stenotic valve depends not only on its limiting orifice area but also
      on its three-dimensional geometry proximal to the orifice. This can affect the
      coefficient of orifice contraction (Cc = effective/anatomic area), which is
      important because for a given flow rate and anatomic area, a lower Cc gives a
      higher velocity and pressure gradient, and Cc, routinely assumed constant in the
      Gorlin equation, may vary with valve shape (60% for a flat plate, 100% for a
      tube). To date, it has not been possible to study this with actual valve shapes
      in patients. METHODS AND RESULTS: Three-dimensional echocardiography
      reconstructed valve geometries typical of the spectrum in patients with mitral
      stenosis: mobile doming, intermediate conical, and relatively flat immobile
      valves. Each geometry was constructed with orifice areas of 0.5, 1.0 and 1.5 cm2
      by stereolithography (computerized laser polymerization) (total, nine valves) and
      studied at physiological flow rates. Cc varied prominently with shape and was
      larger for the longer, tapered dome (more gradual flow convergence proximal and
      distal to the limiting orifice): for an anatomic orifice of 1.5 cm2, Cc increased
      from 0.73 (flat) to 0.87 (dome), and for an area of 0.5 cm2, from 0.62 to 0.75.
      For each shape, Cc increased with increasing orifice size relative to the
      proximal funnel (more tubelike). These variations translated into important
      differences of up to 40% in pressure gradient for the same anatomic area and flow
      rate (greatest for the flattest valves), with a corresponding variation in
      calculated Gorlin area (an effective area) relative to anatomic values.
      CONCLUSIONS: The coefficient of contraction and the related net pressure loss are
      importantly affected by the variations in leaflet geometry seen in patients with
      mitral stenosis. Three-dimensional echocardiography and stereolithography, with
      the use of actual information from patients, can address such uniquely three
      dimensional questions to provide insight into the relations between cardiac
      structure, pressure, and flows.

PMID- 8759089
TI  - Accurate measurement of left ventricular ejection fraction by three-dimensional
      echocardiography. A comparison with radionuclide angiography.
AB  - BACKGROUND: Three-dimensional echocardiography is a promising technique for
      calculation of left ventricular ejection fraction, because it allows its
      measurement without geometric assumptions. However, few data exist that study its
      reproducibility and accuracy in patients. METHODS AND RESULTS: Twenty-five
      patients underwent radionuclide angiography and three-dimensional
      echocardiography that used the rotational technique (2 degrees interval and ECG
      and respiratory gating). Left ventricular volume and ejection fraction were
      calculated by use of Simpson's rule at a slice thickness of 3 mm. Analyses were
      performed to define the largest slice thickness required for accurate calculation
      of left ventricular volume and ejection fraction. Three-dimensional
      echocardiography showed excellent correlation with radionuclide angiography for
      calculation of left ventricular ejection fraction (mean +/- SD, 38.9 +/- 19.8 and
      38.5 +/- 18.0, respectively; r = .99); their mean difference was not significant
      (0.03 +/- 0.17; P = .3), and they had a close limit of agreement (-0.385, 0.315).
      Intraobserver variability for radionuclide angiography and three-dimensional
      echocardiography was 4.2% and 2.6%, respectively, whereas interobserver
      variability was 6.2% and 5.3%, respectively. There was no significant difference
      between left ventricular volume and ejection fraction calculated at a slice
      thickness of 3 mm and that calculated at different slice thicknesses up to 24 mm.
      However, the standard deviation of the mean difference showed a stepwise
      increase, particularly at thicknesses > 15 mm. At a slice thickness of 15 mm, the
      probability of three-dimensional echocardiography to detect > or = 6% difference
      in ejection fraction was 80%. CONCLUSIONS: Three-dimensional echocardiography has
      excellent correlation with radionuclide angiography for calculation of left
      ventricular ejection fraction in patients and has an observer variability similar
      to that of radionuclide angiography. We recommend the use of a 15-mm-thick slice
      for accurate and rapid measurement of left ventricular volume and ejection
      fraction.

PMID- 8759090
TI  - Extent of clinical improvement after surgical treatment of hypertrophic
      obstructive cardiomyopathy.
AB  - BACKGROUND: A subgroup of patients with hypertrophic obstructive cardiomyopathy
      remain severely symptomatic despite optimal medical therapy. Septal myectomy
      reduces or eliminates left ventricular outflow obstruction and produces marked
      symptomatic improvement. With the recent advent of alternative methods for
      treatment of this disorder, such as dual-chamber pacing, it is necessary to
      establish the risks and benefits of septal myectomy in the modern surgical era.
      METHODS AND RESULTS: The clinical, ECG, echocardiographic, cardiac
      catheterization, and surgical data were analyzed for 65 patients 20 to 70 years
      old with hypertrophic obstructive cardiomyopathy who had surgical treatment
      between 1986 and 1992. Specific symptoms and overall functional status were
      evaluated before surgery and at the end of the first postoperative year.
      Subsequent long-term clinical postoperative follow-up was also obtained. The
      extent of postoperative improvement was measured by the presence and severity of
      persistent symptoms, overall New York Heart Association (NYHA) functional class,
      and patients' self-perceptions of overall improvement. Of the patients, 95% were
      in NYHA functional class III or IV before surgery: 95% had dyspnea, 62% had
      angina, 63% had near-syncope, and 23% had syncope. The overall early mortality
      rate was 4.6%; there was no mortality among the 45 patients who underwent
      isolated septal myectomy. At the 1-year postoperative evaluation, 89% of
      survivors were in NYHA functional class I or II, and 47% believed that they had
      100% improvement. Significant improvement (as defined) was seen in 67% of
      patients with dyspnea, 90% with angina, 86% with near-syncope, and 100% with
      syncope. The 5-year survival rate was 92%. CONCLUSIONS: The results of the
      present study reaffirm the efficacy of surgical treatment of hypertrophic
      obstructive cardiomyopathy in patients who are severely symptomatic despite
      optimal medical therapy and serve as a useful reference by which the surgical
      approach can be compared with new and potentially promising treatment
      alternatives.

PMID- 8759091
TI  - Cardiac troponin T isoform expression correlates with pathophysiological
      descriptors in patients who underwent corrective surgery for congenital heart
      disease.
AB  - BACKGROUND: This study examined cardiac troponin T (cTnT) isoform expression in
      patients who had undergone surgery at Duke University Medical Center (Durham, NC)
      between December 1, 1993, and January 31, 1995, to correct congenital heart
      defects. The human heart expresses four cTnT isoforms (cTnT1 through cTnT4) whose
      sequence differences result from combinatorial alternative splicing of two exons.
      We have previously shown that cTnT4 is expressed at higher levels in severely
      failing hearts from transplant patients. In this study, we tested the hypothesis
      that congenital heart defects that have a more negative effect on myocardial
      function increase cTnT4 expression. We used the presence or absence of drug
      treatment for heart failure or congested circulation before surgery and the
      duration of inotropic support after corrective surgery as indicators of the
      pathophysiological state of the heart just before surgery. METHODS AND RESULTS:
      Right atrial appendage tissue was collected from 34 patients, 6 days to 35 years
      old (median age, 3.4 months). The amounts of the cTnT1 through cTnT4 isoforms,
      measured as a percentage of total cTnT, were determined from Western blots probed
      with MAb13-11, a cTnT-specific monoclonal antibody. We found that cTnT4
      expression correlated positively with the duration of inotropic support and was
      higher in patients who received drug treatment before surgery than in those who
      did not. Furthermore, we found that the percent of cTnT4 was significantly higher
      in hearts with congenital defects that caused congestive failure than in hearts
      with tetralogy of Fallot. CONCLUSIONS: These findings suggest that in patients
      with congenital cardiac defects, cTnT4 expression is modulated by heart failure
      and is increased in hearts that are more hemodynamically stressed.

PMID- 8759092
TI  - Acute hemodynamic responses to inhaled nitric oxide in patients with limited
      scleroderma and isolated pulmonary hypertension.
AB  - BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator that
      reduces pulmonary vascular resistance (PVR) in patients with primary pulmonary
      hypertension. Their responses to inhaled NO predict their responses to other
      vasodilators, such as prostacyclin, and provide an estimate of the "fixed"
      component of their increased PVR. Some patients with limited cutaneous systemic
      sclerosis develop isolated pulmonary hypertension with a similar clinical course.
      Therefore, we have measured the acute hemodynamic response to inhaled NO in such
      patients. METHODS AND RESULTS: Seven patients were studied during inhalation of
      increasing concentrations of NO (0 to 80 ppm). Complete hemodynamic data were
      collected on five patients. They demonstrated a selective, dose-dependent, and
      rapidly reversible fall in PVR (34%) and mean pulmonary artery pressure (17%).
      There was a nonsignificant increase in cardiac index but no change in mean
      arterial pressure or systemic vascular resistance. The mean right atrial pressure
      fell (27%), but there was no change in pulmonary artery occlusion pressure. Of
      the seven patients, five responded to inhaled NO ( < or = 40 ppm) with a decrease
      in total pulmonary resistance of at least 20%. CONCLUSIONS: Inhaled NO is an
      effective and selective pulmonary vasodilator in a significant number of patients
      with pulmonary hypertension associated with limited cutaneous systemic sclerosis.
      It may be useful in determining the potentially reversible contribution to the
      increased PVR and should be considered for patients with acute pulmonary vascular
      crisis.

PMID- 8759093
TI  - Prospective study of oral contraceptives and hypertension among women in the
      United States.
AB  - BACKGROUND: Oral contraceptives induce hypertension in approximately 5% of users
      of high-dose pills that contain at least 50 micrograms estrogen and 1 to 4 mg
      progestin, and small increases in blood pressure have been reported even among
      users of modern low-dose formulations. However, neither the responsible hormone
      in the oral contraceptive nor particular subgroups of women who might be
      susceptible to the hypertensive effect of oral contraceptives have been
      identified. METHODS AND RESULTS: In a prospective cohort study in the United
      States, 68 297 female nurses aged 25 to 42 years and free of diagnosed
      hypertension, diabetes, coronary heart disease, stroke, and cancer at baseline
      were followed up for 4 years. During 231 006 person-years of follow-up, 1567
      incident cases of hypertension were diagnosed. Compared with women who had never
      used oral contraceptives, the age-adjusted relative risk was 1.5 (95% CI = 1.2 to
      1.8) for current use and 1.1 (95% CI = 0.9 to 1.2) for past use. After adjustment
      for age, body mass index, hormones cigarette smoking, family history of
      hypertension, parity, physical activity, alcohol intake, and ethnicity, current
      users of oral contraceptives had an increased risk of development of hypertension
      (RR = 1.8; 95% CI = 1.5 to 2.3) compared with women who had never used them. The
      multivariate relative risk for past users was 1.2 (95% CI = 1.0 to 1.4). There
      were no important modifying effects of age, family history of hypertension,
      ethnicity, or body mass index. CONCLUSIONS: Current users of oral contraceptives
      had a significant, moderately increased risk of hypertension. However, among this
      group, only 41.5 cases per 10 000 person-years could be attributed to oral
      contraceptive use. Risk decreased quickly with cessation of oral contraceptives,
      and past users appeared to have only a slightly increased risk.

PMID- 8759094
TI  - Local venous responses to endotoxin in humans.
AB  - BACKGROUND: Septic shock is characterized by arterial and venous dilatation and
      decreased responsiveness to vasoconstrictors. We have developed a method to
      explore the effects and mechanisms of action of administration of endotoxin into
      a blood vessel in vivo. METHODS AND RESULTS: Endotoxin was instilled into a
      dorsal hand vein for 1 hour and then removed. A dose-response curve to
      norepinephrine was constructed before and 1, 2, 3, and 4 hours after endotoxin.
      In a separate study, dose-response curves to norepinephrine were constructed in
      two separate veins on the same hand, only one of which received endotoxin.
      Sympathetic-mediated venoconstrictor responses were also studied. Cyclooxygenase
      inhibitors, nitric oxide synthase inhibitors, and hydrocortisone were used to
      explore the mechanisms of the effects seen. Endotoxin caused a rightward shift in
      the dose-response curve to norepinephrine. The effect was greatest at 1 hour
      (maximal constriction: before endotoxin, 87 +/- 4%; after endotoxin, 52 +/- 8%;
      occlusion n = 4; P < .05) and returned to normal by 4 hours. In addition, deep
      breath venoconstrictor responses were abolished in the endotoxin-treated vein.
      Instillation of endotoxin daily for 3 days resulted in the development of
      tolerance (maximal constriction to norepinephrine after endotoxin; day 1, 39 +/-
      6%; day 2, 67 +/- 7%; day 3, 85 +/- 7%). Cyclooxygenase and/or nitric oxide
      synthase inhibitors did not alter the response to endotoxin, whereas prior
      administration of hydrocortisone abolished the effects. CONCLUSIONS: Instillation
      of endotoxin caused a glucocorticoid-inhibitable hyporesponsiveness to the
      constrictor effects of norepinephrine and abolished sympathetically induced and
      drug-induced venoconstriction. This acute response does not appear to be mediated
      by nitric oxide or prostanoids. Direct vascular tolerance to endotoxin occurs on
      repeated administration.

PMID- 8759095
TI  - Effects of dietary L-arginine on atherosclerosis and endothelium-dependent
      vasodilatation in the hypercholesterolemic rabbit. Response according to
      treatment duration, anatomic site, and sex.
AB  - BACKGROUND: Nitric oxide (NO) may protect arteries against atherosclerosis. In
      the present study, we examined whether dietary L-arginine, the precursor of NO,
      could chronically preserve endothelium-dependent vasodilatation in vivo and/or
      limit atherogenesis. METHODS AND RESULTS: Rabbits were randomized according to
      sex to receive 2% dietary cholesterol, with or without L-arginine (2.25%
      solution), for 7 or 14 weeks. Hindlimb vasodilator responses to acetylcholine and
      nitroprusside were measured with an electromagnetic flow probe. Atherosclerosis
      was measured with planimetry of aortic lesions stained with Oil-Red-O. In rabbits
      administered L-arginine, plasma arginine levels increased to 483 +/- 30 mumol/L
      at 3 weeks (mean +/- SEM, P < .0001 versus control animals) but declined to 224
      +/- 25 mumol/L at 7 weeks (P = .02) and to 100 +/- 23 mumol/L at 14 weeks (NS
      versus control animals). At 7 weeks, peak hindlimb conductance in response to
      acetylcholine in cholesterol-fed males was 249 +/- 49% of baseline compared with
      332 +/- 9% in control animals (P = .04), but peak response in arginine-fed
      rabbits (314 +/- 24%) did not differ from that of control animals. At 14 weeks,
      peak responses to acetylcholine were equally reduced in males fed cholesterol
      with (266 +/- 21%, P = .02 versus control) or without (263 +/- 13%, P = .01
      versus control) L-arginine. Similar impairment of endothelium-dependent
      vasodilatation was seen in females at 14 weeks. Vasodilator responses to
      nitroprusside did not differ from those of control animals in any treatment
      group. After 14 weeks, atherosclerosis was less in the descending aorta of
      arginine-fed males (16 +/- 4% surface area) than that of males fed cholesterol
      only (42 +/- 8%, P = .04), but no treatment benefit was seen in the ascending
      aorta or in females. CONCLUSIONS: Dietary L-arginine supplementation causes an
      early rise in plasma arginine levels, with limitation of atherosclerosis in the
      descending aorta and preservation of endothelium-dependent vasodilatation in
      resistance arteries, but this treatment effect is not sustained. Dietary L
      arginine may not be of long-term benefit in the prevention of atherosclerosis in
      humans.

PMID- 8759096
TI  - Functional and structural alterations with 24-hour myocardial hibernation and
      recovery after reperfusion. A pig model of myocardial hibernation.
AB  - BACKGROUND: Short-term myocardial hibernation of 3 hours resulting from a
      moderate resting coronary flow reduction has been reproduced in pigs. This study
      was designed to determine whether any structural changes accompany short-term
      hibernation caused by a moderate flow reduction maintained for 24 hours and
      whether any such structural alterations are reversible after reperfusion. METHODS
      AND RESULTS: A severe left anterior descending coronary artery (LAD) stenosis was
      created with a reduction of resting flow to approximately 60% of baseline and
      maintained for 24 hours. Regional coronary flow was measured by a flowmeter; wall
      thickening was determined by echocardiography, and local metabolic changes were
      measured. Of 17 pigs, 11 completed the study protocol of 24 hours. The LAD flow
      was reduced from 0.91 +/- 0.11 to 0.52 +/- 0.13 mL.min-1.g-1, a 43% mean
      decrease, at 15 minutes after the LAD stenosis and was maintained at 0.56 +/-
      0.11 mL.min-1.g-1 at 24 hours. The reduction of regional coronary flow initially
      produced acute myocardial ischemia, as evidenced by reduced regional wall
      thickening (from 37.2 +/- 6.9% at baseline to 11.5 +/- 6.8%), regional lactate
      production (-0.34 +/- 0.28 mumol.g-1.min-1), and a decrease in regional coronary
      venous pH (from 7.41 +/- 0.035 at baseline to 7.30 +/- 0.030). At 24 hours, the
      reductions in coronary flow and wall thickening were maintained relatively
      constant and the rate-pressure product was relatively unchanged, but lactate
      production ceased and regional H+ concentration normalized, with a tendency
      toward a further reduction in regional oxygen consumption, from 3.10 +/- 0.90
      mL.min-1.100 g-1 at 15 minutes after stenosis to 2.52 +/- 0.95 mL.min-1.100 g-1
      at 24 hours (P = .06), indicating metabolic adaptation of the hypoperfused
      regions. Of 11 pigs, 6 were free of myocardial infarction; 3 had patchy necrosis
      involving 4%, 5%, and 6% of the area at risk; and 2 other pigs had a few
      scattered myocytes with necrosis, detected only by light and electron microscopy.
      Ultrastructural changes consisted of a partial loss of myofibrils and an increase
      in mitochondria and glycogen deposition. Regional wall thickening recovered 1
      week after reperfusion in most pigs, and the ultrastructural changes reverted to
      normal. CONCLUSIONS: In this pig model, moderately ischemic myocardium undergoes
      metabolic and structural adaptations but preserves the capacity to recover both
      functionally and ultrastructurally after reperfusion.

PMID- 8759097
TI  - Bradykinin and its metabolite, Arg-Pro-Pro-Gly-Phe, are selective inhibitors of
      alpha-thrombin-induced platelet activation.
AB  - BACKGROUND: Plasma kininogens are selective inhibitors of alpha-thrombin
      activation of platelets and endothelial cells. In the present study, we localized
      the alpha-thrombin inhibitory sequence of kininogens and describe its mechanism
      of action. METHODS AND RESULTS: Bradykinin and an analogue, MKRPPGFSPFRSSRIG,
      inhibited alpha-thrombin-induced platelet aggregation and secretion with an IC50
      of 0.25 and 1 mmol/L and of 0.23 and 0.5 mmol/L, respectively. The minimal
      inhibitory peptide was RPPGF. Bradykinin and its analogues did not inhibit ADP-,
      collagen-, U46619-, or SFLLRN-induced platelet activation or the ability of alpha
      thrombin to cleave chromogenic substrates, clot fibrinogen, or block alpha
      thrombin binding to platelets. Bradykinin, MKRPPGFSPFRSSRIG, and RPPGF abolished
      alpha-thrombin-induced (1 nmol/L) calcium mobilization. On flow cytometry,
      bradykinin and MKRPPGFSPFRSSRIG blocked alpha-thrombin from removing the epitope
      of its cleavage site on the cloned thrombin receptor. Furthermore, peptide RPPGF
      or high-molecular-weight kininogen prevented alpha-thrombin from cleaving the
      thrombin receptor peptide, NATLDPRSFLLR, between arginine and serine.
      CONCLUSIONS: These results indicate that bradykinin and its metabolites are
      selective antithrombins by preventing alpha-thrombin cleavage of the cloned
      thrombin receptor between arginine-41 and serine-42. These newly recognized
      antithrombin peptides, which are termed thrombostatins, contribute to the
      cardioprotective nature of kinins.

PMID- 8759098
TI  - Cardiac vagal reflex modulates intestinal vascular capacitance and ventricular
      preload in anesthetized dogs with acute myocardial infarction.
AB  - BACKGROUND: The purpose of the present study was to examine the effects of the
      cardiac vagal reflex on intestinal vascular capacitance and cardiac filling
      pressure during experimental acute myocardial infarction (AMI). METHODS AND
      RESULTS: AMI was induced in anesthetized dogs through injection of microspheres
      into the left main coronary artery. Intestinal blood volume was measured with
      blood-pool scintigraphy. Portal venous pressure was varied through graded
      inflation of a portal venous constrictor to determine the intestinal vascular
      pressure-volume relation. Induction of AMI decreased intestinal blood volume to
      88 +/- 3% of the control value (P < .01) and shifted the pressure-volume relation
      toward the pressure axis. This change was associated with increased left
      ventricular (LV) end-diastolic pressure (LVEDP) (from 6 +/- 1 to 17 +/- 2 mm Hg,
      P < .01) and LV segment length (to 112 +/- 4% of the control value, P < .01).
      During AMI, blockade of the cardiac vagal reflex by intrapericardial application
      of 2% lidocaine further decreased intestinal blood volume (to 83 +/- 3% of the
      control value, P < .05, versus AMI without lidocaine), increased LVEDP (to 22 +/-
      2 mm Hg, P < .05, versus AMI without lidocaine), and tended to increase LV
      segment length (to 115 +/- 5%, P < .10). Lidocaine had no effect in dogs with AMI
      that had been vagotomized. CONCLUSIONS: These results suggest that the cardiac
      vagal reflex modulates the decrease in the intestinal vascular capacitance
      induced by AMI and modulates ventricular preload through pooling of blood in the
      intestinal circulation.

PMID- 8759099
TI  - Mechanism of the systemic, left ventricular, and coronary vascular tolerance to a
      binge of cocaine in conscious dogs.
AB  - BACKGROUND: Prior experimental studies have emphasized the cardiovascular effects
      of acute, single doses of cocaine. However, cardiovascular complications are most
      often reported in chronic users, who have been exposed to repetitive doses of
      cocaine. It remains unclear whether there is tolerance or sensitization to the
      systemic, left ventricular, and coronary hemodynamic effects of a binge of
      cocaine. METHODS AND RESULTS: We studied 11 conscious, chronically instrumented
      dogs to determine the systemic pressor, inotropic, chronotropic, and coronary
      vascular resistance responses to cocaine (1 mg/kg IV) administered every 25
      minutes for five doses. There was progressive tolerance to the systemic pressor
      (mean arterial pressure: first dose, +42 +/- 4% from 97 +/- 2 mm Hg; fifth dose,
      +8 +/- 3% from 116 +/- 7 mm Hg; P < .01) and heart rate (first dose, +45 +/- 8%
      from 93 +/- 5 bpm; fifth dose, +8 +/- 2% from 109 +/- 9 bpm; P < .01) responses
      and abolition of the positive inotropic (left ventricular dP/dt: first dose, +19
      +/- 4% from 2824 +/- 75 mm Hg/s; fifth dose, -3 +/- 5% from 2531 +/- 436 mm Hg/s;
      P < .01) and coronary vasoconstrictor (coronary vascular resistance: first dose,
      +38 +/- 9% from 1.9 mm Hg.mL-1.min-1; fifth dose, -7 +/- 2% from 2.6 +/- 0.2 mm
      Hg. mL-1.min-1; P < .01) responses to a binge of cocaine despite progressive
      increases in peak plasma cocaine concentrations. In contrast, both the plasma
      norepinephrine and epinephrine responses were attenuated with repetitive exposure
      to cocaine, whereas myocardial alpha and beta-adrenergic responsiveness was
      maintained. CONCLUSIONS: Repetitive cocaine administration is associated with the
      development of early and progressive tolerance to systemic, left ventricular, and
      coronary vascular effects of cocaine. The mechanism of the tolerance involves
      neither impaired myocardial nor coronary vascular responsiveness to adrenergic
      stimulation but, rather, attenuated catecholamine responses to repetitive cocaine
      administration.

PMID- 8759100
TI  - An oligosaccharide sialyl-Lewis(x) analogue does not reduce myocardial infarct
      size after ischemia and reperfusion in dogs.
AB  - BACKGROUND: Polymorphonuclear leukocytes, particularly neutrophils, are important
      mediators of ischemia/reperfusion-induced myocardial and coronary vascular
      injury. The selectin family of glycoprotein receptors mediates neutrophil
      "rolling," a loose, transient adhesion to the coronary endothelium that precedes
      the firmer adhesion associated with cardiovascular injury. The oligosaccharide
      sialyl-Lewis(x) (SLe(x)) is the probable neutrophil counterligand for endothelial
      E- and P-selectin. Administration of analogues of SLe(x) could potentially
      prevent neutrophil rolling by competing for the selectin-adhesion sites. We
      investigated the effects of treatment with an analogue of SLe(x) in a chronic
      canine model of ischemia/reperfusion. METHODS AND RESULTS: Anesthetized mongrel
      dogs were subjected to 90 minutes of ischemia through occlusion of the left
      anterior descending coronary artery and 48 hours of reperfusion. Five minutes
      before the onset of reperfusion, dogs received either the SLe(x) analogue CY-1503
      at a dose of 20 mg/kg or normal saline. Myocardial infarct size was measured
      through triphenyltetrazolium chloride staining, and polymorphonuclear leukocyte
      accumulation was evaluated through measurement of cardiac myeloperoxidase
      activity. After adjustment for blood flow, the mean infarct size of control dogs
      (44.7 +/- 4.2%) was not different from that of treated dogs (33.4 +/- 4.0%, P =
      .06), although there was a trend toward a slightly lower value in the treated
      dogs. Myeloperoxidase activity was not different in the infarcted myocardium of
      the treated group compared with that of the control group (2.7 +/- 0.71 treated
      versus 1.08 +/- 0.41 units/mg protein control, P = .06). CONCLUSIONS: We conclude
      that CY-1503 does not substantially or consistently reduce myocardial infarct
      size or neutrophil accumulation in dogs subjected to ischemia followed by a
      prolonged period (48 hours) of reperfusion.

PMID- 8759102
TI  - Pleural and pericardial pressures limit fetal right ventricular output.
AB  - BACKGROUND: The chest wall, lungs, and pericardium limit diastolic filling of the
      left ventricle in the fetus, neonate, and adult. To determine the effect that
      these tissues have on the fetal right ventricle (RV), we studied six fetal lambs
      (142 days of gestation) METHODS AND RESULTS: Pregnant ewes were anesthetized
      (ketamine and alpha-chloralose), and the fetuses were partially delivered by
      cesarean section. Fetuses were instrumented to record RV stroke volume, RV end
      diastolic pressure (Prved), intrapericardial pressure (Pip), and pleural
      pressure. Prved was varied between 2 and 20 mm Hg under three conditions:
      initially with a closed chest and a closed pericardium (CCCP); subsequently with
      an open chest (chest wall and lungs retracted) and a closed pericardium (OCCP);
      and finally after the chest wall, lungs, and pericardium were retracted (OCOP).
      At equal Prved, stroke volume increased substantially when the chest wall and
      lungs were retracted from the heart and increased further on subsequent
      retraction of the pericardium (eg, at Prved of 9 mm Hg, stroke volume increased
      from 1.2 +/- 0.2 mL [mean +/- SEM] in the CCCP condition to 2.9 +/- 0.4 and 4.2
      +/- 0.3 mL in the OCCP and OCOP conditions, respectively, P < or = .05). The
      limitation of stroke volume in the CCCP and OCCP conditions occurred because Pip
      increased in an almost one-to-one fashion as Prved increased; as a consequence,
      RV preload (RV end-diastolic transmural pressure, Prved minus Pip) was relatively
      unchanged. CONCLUSIONS: The chest wall-lung combination and the pericardium each
      significantly constrain the fetal RV and together limit RV stroke volume.

PMID- 8759101
TI  - Mechanism of catecholamine-induced proliferation of vascular smooth muscle cells.
AB  - BACKGROUND: Catecholamines have been shown to aggravate atherosclerosis in
      animals and humans, and abnormal proliferation of vascular smooth muscle cells
      (VSMC) is a key event in the early stage of atherosclerosis. Catecholamines may
      be involved in such cell growth. Therefore, a series of experiments using
      cultured VSMC was performed to elucidate their possible mitogenic effect. METHODS
      AND RESULTS: We examined the mitogenic effect of catecholamines using rat aortic
      smooth muscle cells (VSMC) by measuring [3H]thymidine incorporation, checking
      with flow cytometry, and counting the cell number directly. Furthermore, the
      catecholamine-activated signal transduction pathway was assessed by measurement
      of the formation of inositol 1, 4, 5-triphosphate, intracellular Ca2+
      concentration, mitogen-activated protein kinase (MAPK) activity, and mitogenic
      gene expression. Norepinephrine (NE) and phenylephrine stimulated [3H]thymidine
      incorporation and cell growth. Clonidine and isoproterenol showed little of such
      effects. Prazosin was more effective than either yohimbine or propranolol in
      suppressing the mitogenic effect of NE, indicating that catecholamine-induced
      VSMC proliferation is mediated by alpha 1-adrenoceptors. The alpha 1-adrenoceptor
      activation was coupled to pertussis toxin-insensitive Gq-protein and triggered
      phosphoinositide hydrolysis with subsequent activation of protein kinase C and
      MAPK in VSMC. In response to NE, both 42- and 44-kD MAPK were activated and
      tyrosine was phosphorylated. alpha 1-Adrenoceptor stimulation with NE also caused
      accumulation of c-fos, c-jun, and c-myc mRNA. Chloroethylclonidine completely
      blocked the alpha 1-adrenoceptor-mediated mitogenesis. CONCLUSIONS: The effect of
      catecholamines appears to be mediated via the activation of the
      chloroethylclonidine-sensitive alpha 1-adrenoceptors that triggers the
      phosphoinositide hydrolysis and activates the MAPK pathway, leading to DNA
      synthesis and cell proliferation.

PMID- 8759103
TI  - Class III antiarrhythmic effects of zatebradine. Time-, state-, use-, and voltage
      dependent block of hKv1.5 channels.
AB  - BACKGROUND: Zatebradine is a bradycardic agent that inhibits the
      hyperpolarization-activated current (I(f)) in the rabbit sinoatrial node. It also
      prolongs action potential duration in papillary muscles in guinea pigs and in
      Purkinje fibers in rabbits. The underlying mechanism by which zatebradine induces
      this effect has not been explored, but it is likely to involve K+ channel block.
      METHODS AND RESULTS: Cloned human cardiac K+ delayed rectifer currents (hKv1.5)
      were recorded in Ltk- cells transfected with their coding sequence. Zatebradine
      10 mumol/L did not modify the initial activation time course of the current but
      induced a subsequent decline to a lower steady-state current level with a time
      constant of 109 +/- 16 ms. Zatebradine inhibited hKv1.5 with an apparent KD of
      1.86 +/- 0.14 mumol/L. Block was voltage dependent (electrical distance delta =
      0.177 +/- 0.003) and accumulated in a use-dependent manner during 0.5- and 1-Hz
      pulse trains because of slower recovery kinetics in the presence of the drug.
      Zatebradine reduced the tail current amplitude, recorded at -30 mV, and slowed
      the deactivation time course, which resulted in a "crossover" phenomenon when
      control and zatebradine tail currents were superimposed. CONCLUSIONS: These
      results indicate that (1) zatebradine is an open-channel blocker of hKv 1.5, (2)
      binding occurs in the internal mouth of the ion pore, (3) unbinding is required
      before the channel can close, and (4) zatebradine-induced block is use dependent
      because of slower recovery kinetics in the presence of the drug. These effects
      may explain the prolongation of the cardiac action potential and could be
      clinically relevant.

PMID- 8759104
TI  - Atrioventricular junctional tissue. Discrepancy between histological and
      electrophysiological characteristics.
AB  - BACKGROUND: Previous work has demonstrated that cells with AV nodal-type action
      potentials are not confined to Koch's triangle but may extend along the AV
      orifices. The aim of this study was to examine the histological and
      electrophysiological characteristics of this tissue. METHODS AND RESULTS: Studies
      were performed in isolated, blood-perfused dog and pig hearts. Microelectrode
      recordings revealed cells with nodal-type action potentials around the tricuspid
      and mitral valve rings. These cells were found within 1 to 2 mm of the valve
      annuli. A zone of cells with intermediate action potentials, approximately 1 cm
      wide, separated cells with nodal-type action potentials from cells with atrial
      type action potentials in the body of the atria. In cells with nodal-type action
      potentials, adenosine caused a reduction in action potential amplitude (49 +/- 2
      versus 33 +/- 2 mV, mean +/- SE; P < .001), upstroke velocity (2.5 +/- 0.2 versus
      2.0 +/- 0.2 V/s, P < .05), and duration (150 +/- 4 versus 96 +/- 8 ms, P < .001).
      The light microscopic appearance of AV junctional cells was similar to that of
      myocytes in the body of the atrium. A polyclonal antibody raised against connexin
      43 bound to atrial and ventricular tissue but not to the AV junctional tissue or
      AV nodal region. The absence of connexin-43 correlated with the sites of cells
      with nodal-like action potentials. With pacing techniques, the AV junctional
      tissue in the region of the posterior AV nodal approaches could be electrically
      dissociated from atrial, AV nodal, and ventricular tissue. AV nodal echoes were
      induced with ventricular pacing in three dog hearts. In each case, retrograde
      conduction was through the slow pathway, and anterograde conduction was through
      the fast pathway. During echoes, activation of AV junctional cells preceded
      atrial activation during retrograde slow pathway conduction, but these cells were
      not activated during anterograde fast pathway conduction. CONCLUSIONS: AV
      junctional cells around both annuli are histologically similar to atrial cells
      but resemble nodal cells in their cellular electrophysiology, response to
      adenosine, and lack of connexin-43. The light microscopic appearance of AV
      junctional cells is a poor guide to their action potential characteristics. The
      AV junctional cells in the posterior AV nodal approaches appear to participate in
      slow pathway conduction. These cells may be the substrate of the slow "AV nodal"
      pathway.

PMID- 8759105
TI  - Dual-chamber versus ventricular pacing. Critical appraisal of current data.

PMID- 8759106
TI  - Additional information on solving the riddle of phentolamine's action.

PMID- 8759107
TI  - Measurement of intracardiac pressures.

PMID- 8759108
TI  - Double ventricular responses during AV nodal reentrant tachycardia or other
      mechanism.

PMID- 8759109
TI  - Detection of intralesional calcium in coronary arteries.

PMID- 8759110
TI  - HCM in the general population.

PMID- 8759111
TI  - Assessment of coronary vasoreactivity.

PMID- 8759112
TI  - Assignment of markers by using polymerase chain reaction on pools of swine flow
      sorted chromosomes.
AB  - Gene chromosomal assignment can be realized not only by somatic hybrid panels but
      also by spot-blot hybridization or polymerase chain reaction (PCR) of flow-sorted
      chromosomes. We propose a swine chromosome assignment strategy by PCR
      amplification on pooled chromosomal DNA, which allows assignment despite possible
      chromosomal contamination during sorting. Each pool contains three different
      chromosomes, each chromosome being present in one or two pools. We present
      concordant results obtained for eight markers already mapped to different swine
      chromosomes and we assign the somatostatin gene to chromosome 13, a new marker in
      the pig genome.

PMID- 8759113
TI  - Cloning and characterization of 414 polymorphic porcine microsatellites.
AB  - We report the sequences, sizes, and number of alleles of 414 new porcine
      microsatellites that were cloned in our laboratory and 21 microsatellites derived
      from GenBank DNA sequences. We also confirm the usefulness of porcine
      microsatellite primer pairs derived from short interdispersed elements.

PMID- 8759114
TI  - A search for quantitative trait loci for ovulation rate in cattle.
AB  - Seventy-seven polymorphic microsatellites were analysed in offspring of three
      elite sires that were part of the foundation of an experimental population
      selected for twinning rate at the US Meat Animal Research Center, Clay Center,
      Nebraska. All females were assessed for ovulation rate by rectal palpation of
      corpora lutea over 8-10 consecutive oestrous cycles from approximately 12 to 18
      months of age, and associations between ovulation rate and sire allele were
      examined in each of the three sire groups. A preliminary analysis was performed
      using selectively genotyped daughters of each sire. Markers found significant or
      approaching significance were also genotyped in all daughters, sons and
      granddaughters of these sires. A test of marker associations limited to the
      granddaughter data provided an independent confirmation of marker effect and
      significance relative to the initial test with daughter data. Putative ovulation
      rate quantitative trait loci were detected on chromosomes 7 and 23. Marker UWCA20
      on chromosome 7 was associated with an effect in excess of one phenotypic
      standard deviation and accounted for approximately 10% of phenotypic variation
      ovulation rate. Marker CYP21 (steroid 21-hydroxylase) on chromosome 23 was
      associated with an effect of slightly less than half a phenotypic standard
      deviation and accounted for approximately 4% of phenotypic variation.

PMID- 8759115
TI  - The bovine butyrophilin gene maps to chromosome 23.
AB  - Chromosomal assignment of the bovine butyrophilin gene (BTN) was performed by
      analysis of DNA from somatic hybrid cell lines using the polymerase chain
      reaction. The gene was assigned to bovine chromosome 23 using two sets of primers
      specific for bovine BTN.

PMID- 8759116
TI  - Linkage mapping of the retinoic acid receptor-gamma gene to porcine chromosome 5.
AB  - The porcine retinoic acid receptor-gamma gene (RARG) has been mapped by
      restriction fragment length polymorphism analysis to porcine chromosome 5. The
      placement of RARG distal to the diacylglycerol kinase gene increases the length
      of the existing map (PiGMaP) and adds a fifth type-I marker to this sparsely
      mapped chromosome. This augments the homology of pig chromosome 5 and human
      chromosome 12 established by previous comparative mapping.

PMID- 8759117
TI  - Allele frequencies of the major milk proteins in the Finnish Ayrshire and
      detection of a new kappa-casein variant.
AB  - A total of 20990 Finnish Ayrshire cows were phenotyped for the major milk
      proteins by isoelectric focusing in polyacrylamide gels. The predominant alleles
      in the Finnish Ayrshire were alpha S1-casein B (0.999), alpha S2-casein A
      (0.991), beta-casein A1 (0.509) and alpha 2 (0.490), kappa-casein A (0.612) and
      beta-lactoglobulin B (0.716). The kappa-casein E allele (0.307) was also rather
      common in the Finnish Ayrshire. A new kappa-casein variant (kappa-casein F) was
      demonstrated in two Finnish Ayrshire cows, a dam and a daughter.

PMID- 8759118
TI  - Restriction fragment length polymorphism in amplification products of the bovine
      butyrophilin gene: assignment of bovine butyrophilin to bovine chromosome 23.
AB  - A polymorphism was identified in the bovine butyrophilin (BTN) gene by digesting
      polymerase chain reaction products with the restriction enzyme HaeIII. This
      polymorphism was segregating in a Holstein-Friesian sire selected as part of an
      ongoing study directed towards the identification of quantitative trait loci
      affecting milk composition. Screening of a half-sib family established for the
      heterozygous sire allowed the localization of BTN to bovine chromosome 23
      (BTA23).

PMID- 8759119
TI  - Integration of the PiGMaP and USDA maps for porcine chromosome 14.
AB  - In order to align two previously published genetic linkage maps, a set of four of
      the United States Department of Agriculture (USDA) microsatellite linkage markers
      was mapped in the International Pig Gene Mapping Project (PiGMaP) reference
      families. Two-point linkage analysis was used between these USDA markers and the
      set of genes and markers previously mapped on the PiGMaP chromosome 14 map.
      Markers with threshold lod scores of three or greater were used for multipoint
      map construction. The USDA and PigGMaP linkage maps of chromosome 14 were aligned
      using the four USDA microsatellite markers along with three markers that are
      common to both maps. The PiGMaP genetic linkage map order for chromosome 14 was
      confirmed and the map was expanded to 193 cM with addition of the new markers.

PMID- 8759122
TI  - Transfer of bovine microsatellites to the cervine (Cervus elaphus).
AB  - Bovine microsatellites were used to amplify DNA of red deer (Cervus elaphus).
      Fourteen of 27 bovine systems (52%) displayed polymorphism, while no (CA)n-repeat
      was detected in seven systems and six systems gave no amplificates in red deer.
      The allele number ranged from 2 to 7, the polymorphism information content
      between 0.24 and 0.76. The results demonstrate that transfer of microsatellite
      systems between families of the same order (artiodactyla) is possible. Molecular
      genetic research will help to clarify the differentiation and ecology of wild
      animals and will contribute to define criteria needed for the preservation of
      endangered species.

PMID- 8759123
TI  - Characterization and linkage mapping of ten sheep microsatellite markers derived
      from a sheep x hamster cell hybrid.
AB  - A cosmid library has been constructed from a sheep x hamster cell hybrid
      containing sheep chromosome t1, rob (6;24). Clones containing sheep DNA were
      identified by hybridizing to a total sheep genomic DNA probe. Small fragments (<
      500 bp) containing (AC)n microsatellites were subcloned and sequenced. Ten
      microsatellite markers were characterized and six were mapped back to chromosomes
      6 and 24. The remaining microsatellites mapped to chromosome 26, which was shown
      to be present in a small proportion of cells of the cell line.

PMID- 8759124
TI  - Simultaneous analysis of bovine kappa-casein and BLAD alleles by multiplex PCR
      followed by parallel digestion with two restriction enzymes.
AB  - An improved and simplified method allowing simultaneous genetic typing of kappa
      casein and CD 18 (bovine leucocyte adhesion deficiency; BLAD) loci has been
      developed. The method is based on the simultaneous amplification of fragments of
      the two groups of alleles by multiplex PCR, and on a concurrent, parallel
      digestion of the products by two restriction enzymes (PstI and HaeIII) in the
      same incubation buffer. Digestion with PstI distinguishes kappa-casein A and B
      alleles and does not cut within any of the BLAD alleles, while digestion with
      HaeIII allows the differentiation between normal and mutant allele variants of
      the CD18 locus. All combinations of the known mutants of the two alleles,
      characterized to the regions amplified and resulting in phenotypic effect, could
      be detected by electrophoretic separation performed on the same agarose gel owing
      to the vast differences in the length of the restriction fragments.

PMID- 8759125
TI  - PCR-SSCP in the ovine calpastatin gene.

PMID- 8759126
TI  - Mononucleotide repeat polymorphism within intron 1 of the bovine interferon-gamma
      gene.

PMID- 8759127
TI  - A PstI RFLP at the bovine INHBA locus.

PMID- 8759128
TI  - A microsatellite (BOBT24) located between the bovine IL4 and IL13 loci is
      polymorphic in cattle and goat.

PMID- 8759129
TI  - RFLPs at the amylase 1 locus in cattle.

PMID- 8759130
TI  - Isolation of a Y-specific bovine DNA fragment using minisatellite-related PCR
      primers.

PMID- 8759131
TI  - Three new polymorphic equine microsatellites: HLM2, HLM3, HLM5.

PMID- 8759133
TI  - Five polymorphic trinucleotide (CCA) bovine microsatellites.

PMID- 8759134
TI  - A second polymorphism in exon 2 of the BoLA-DYA gene.

PMID- 8759135
TI  - Five molecular markers localized by FISH on pig chromosomes.

PMID- 8759136
TI  - Equine dinucleotide repeat loci LEX015-LEX024.

PMID- 8759137
TI  - A BstUI PCR/RFLP in the bovine tyrosinase-related protein-1 (TYRP1) gene.

PMID- 8759138
TI  - UW52 and UW53: polymorphic bovine microsatellites.

PMID- 8759139
TI  - An ovine dinucleotide repeat polymorphism at the RJH1 locus.

PMID- 8759140
TI  - A polymorphic microsatellite locus (AFZ1) derived from a bovine brain cortex cDNA
      library.

PMID- 8759141
TI  - Five bovine polymorphic microsatellite markers (AF1-AF5).

PMID- 8759142
TI  - Polymorphisms and physical locations of three bovine microsatellite loci:
      IOBT395, IOBT528, IOBT1401.

PMID- 8759143
TI  - The history of the International Society for Animal Genetics to 1994.

PMID- 8759144
TI  - Food selection by the domestic cat, an obligate carnivore.
AB  - The domestic cat Felis silvestris catus is the most accessible member of the
      family Felidae for the study of the relationship between food selection and
      nutrition. In contrast to pack-living animals such as the dog, and opportunistic
      omnivores such as the rat, the cat is generally able to maintain its normal body
      weight even when allowed ad libitum access to palatable food by taking small
      meals and adjusting intake according to the energy density of the food(s)
      available. The most extreme adaptations to carnivory discovered to date lie in
      the taste buds of the facial nerve, which are highly responsive to amino acids
      and unresponsive to many mono- and disaccharides. Preferences for particular
      foods can be modified by their relative abundance, their novelty, and by aversive
      consequences such as emesis: the mechanisms whereby these are brought about
      appear to be similar to those used by omnivorous mammals.

PMID- 8759145
TI  - Biogenic monoamines in the freshwater snail, Biomphalaria glabrata: influence of
      infection by the human blood fluke, Schistosoma mansoni.
AB  - The biogenic monoamines, serotonin (5-HT), dopamine (DA) and L-dopa were measured
      using high performance liquid chromatography with electrochemical detection (HPLC
      ED) in the extracts of the central nervous system (CNS) and plasma of uninfected
      freshwater snails, Biomphalaria glabrata, and in snails at 7, 14, 21 and 28 days
      postexposure (PE) to the miracidia of the human blood fluke, Schistosoma mansoni.
      Relative to age-matched uninfected snails, a general depression of biogenic amine
      levels was observed in the plasma (cell-free haemolymph) and the CNS of infected
      snails, especially during the latter phase of the prepatency period. Significant
      decreases were first observed in the CNS of infected snails beginning at Day 14
      PE for DA and 5-HT and Day 21 PE for L-dopa. Parasite-exposed snails also
      exhibited an early and persistent suppression of plasma 5-HT concentrations,
      starting at 7 days PE and continuing throughout the infection test period. In
      order to determine the effect of 5-HT on reproduction and, thereby, establish a
      possible relationship between the observed parasite-induced reduction in 5-HT
      levels and parasitic castration, the effect of exogenous 5-HT on individual
      infected and uninfected B. glabrata was investigated. Repeated treatment with 10
      microM 5-HT promoted both ovulation and oviposition in B. glabrata. Snails
      treated with 5-HT consistently layed more eggs than did sham-treated controls.
      Infected snails that were treated with 5-HT exhibited similar egg-laying rates as
      those of both serotonin-treated and untreated, uninfected snail groups, thus
      reversing the castrating effects of larval infection. These findings suggest that
      5-HT acts as a stimulant for egg production in B. glabrata, and that parasitic
      castration may be due, at least in part, to larval-induced suppression of 5-HT in
      the snail's CNS and plasma during the course of infection with S. mansoni.

PMID- 8759146
TI  - Energetics of vocalization in the African reed frog (Hyperolius marmoratus).
AB  - Rates of oxygen consumption and carbon dioxide release were measured in calling
      and resting painted reed frogs, Hyperolius marmoratus. O2 consumption increased
      linearly with call rate and reached 0.91 ml/g . h at average call rates of 3100
      calls/hr. The respiratory quotient (RQ = VCO2/VO2) was calculated to evaluate
      which metabolic substrates--lipids or carbohydrates--are utilized. Males that
      were not fed for a week had significantly lower RQ's during calling (0.75) than
      recently fed males (0.89) and thus utilized approximately twice as much lipid to
      fuel calling. Whole-body lipid reserves of males collected in the field varied
      considerably. Lipid stores alone would be sufficient to provide energy for a
      median of 15 nights of calling activity at a high density chorus.

PMID- 8759147
TI  - Effects of partial sympathectomy of brown fat or of adrenomedullectomy on
      catecholamine metabolism in cold-reared rats.
AB  - 1) The aim of this work was to study the effects of surgical denervation of the
      interscapular brown adipose tissue (IBAT) and of bilateral adrenal demedullation
      on cold adaptation of rats. 2) After sympathectomy in the 28 degree C rats, there
      were substantial decreases in the IBAT NE basal level and turnover rate but no
      modifications in the heart and adrenals. In the 16 degree C rats there were also
      decreases in the basal level and turnover rate of the IBAT NE but, in addition,
      significant increases in levels and turnover rates of NE in the heart and of
      epinephrine in the adrenals. 3) Bilateral adrenal demedullation led to increases
      in the NE basal level and turnover rate in the IBAT and the heart in the 16
      degree C rats; no effects were observed in the 28 degree C rats. 4) It is
      concluded that in rats born and reared in a mild cold environment a compensatory
      stimulation of catecholamine production and turnover rate occurs in some organs
      after a partial sympathectomy of BAT or bilateral adrenal demedullation.

PMID- 8759148
TI  - Maternal testosterone in the avian egg enhances postnatal growth.
AB  - The eggs of the canary (Serinus canaria) contain variable doses of maternal
      testosterone. The reported experiments investigated whether testosterone
      influences nestling growth and how this interacts with differences of the growth
      of nest mates that are caused by asynchronous hatching. Injections of
      testosterone into the yolk of unincubated eggs enhanced the growth after hatching
      compared to nestlings that had hatched simultaneously from control eggs. These
      differences were established within 22 hr of hatching. Exogenous testosterone
      promoted growth in both sexes and there was no sexual difference in the growth of
      control birds. Testoster-one-treated chicks also begged more often for food.
      Previous studies have shown that the content of maternal testosterone increases
      in each subsequently laid egg in a clutch. Consistent with the results obtained
      by testosterone injections nestlings that hatched from eggs with higher
      concentrations of maternal testosterone grew faster compared to chicks that
      hatched synchronously from eggs with lower testosterone concentrations. However,
      more testosterone did not compensate for reduced growth that was caused by later
      hatching due to asynchronous incubation of clutches. This direct effect of
      maternal testosterone on growth in combination with a flexible onset of
      incubation allows to selectively enhance the growth and fitness of individual
      offspring of a brood.

PMID- 8759149
TI  - Skeletal muscle characteristics of racing reindeer (Rangifer tarandus).
AB  - Samples from the middle gluteal muscle of 3-7-year-old racing reindeer were taken
      before (7 reindeer) and at the end of the racing season (12 reindeer) for
      determination of fibre type composition, activities of citrate synthase (CS), 3
      hydroxyacyl-CoA-dehydrogenase (HAD) and the glycogen content. Muscle samples were
      also taken from 7 female and 18 male reindeer of same age for histochemical
      determination of muscle fibre composition. During the racing season the fibre
      type composition remained unchanged as did the activities of CS and HAD. The high
      activities of CS and HAD together with the high intensity in the NADH
      dehydrogenase stain indicate that the reindeer muscle has a high oxidative
      capacity. The glycogen content increased during the winter which can explain the
      increasing tendency in the transverse fibre area. The racing reindeer had a lower
      percentage of type I fibres and a higher percentage of type IIA fibres than the
      ordinary male reindeer. The differences in the fibre type composition suggest
      that the racing reindeer represent a selected reindeer population.

PMID- 8759150
TI  - Bibliography of Comparative Biochemistry and Physiology A generated from the
      Current Awareness in Biological Sciences database.

PMID- 8759151
TI  - Effect of iron limitation on the amount of slime produced by strains of
      Staphylococcus epidermidis.
AB  - To investigate the effect of iron limitation on the amount of slime production by
      most strains of Staphylococcus epidermidis, ethylenediamine-di-o-hydroxyphenol
      acetic acid (EDDA), was added to the growth medium and twenty clinically relevant
      strains were assayed for slime production during growth in standard tryptic soy
      broth (TSB) and iron-limited TSB. Findings revealed that the density of the
      biofilm which formed on the base of microtitre plates was dependent on the degree
      of iron limitation, characteristics of the test strains and the stage of the
      growth cycle.

PMID- 8759152
TI  - Haematoporphyrin and proflavine-sensitized photoinactivation of Salmonella
      dublin.
AB  - The photosensitive activity of haematoporphyrin (HP) and proflavine (PF) on some
      biological parameters of Salmonella dublin cells was assessed. The investigations
      showed a decreased respiratory activity of photosensitized PF bacterial cells,
      accompanied by lower virulence. HP-treatment and light irradiation of salmonellae
      did not influence their survival in vitro, which was in contrast to the PF
      incubated and irradiated cells. Light irradiation of HP- and PF-treated bacteria
      did not change their phagocytosis from guinea pig alveolar macrophages. In the
      presence of visible light the PF-treatment considerably reduced the survival rate
      and multiplication in alveolar macrophages in comparison with HP-treated and
      light-exposed bacteria. Correlation was established between the degree of
      structural damage, as observed by electron microscopy and the level of diminution
      of the chosen biological parameters, which were more strongly expressed after PF
      treatment. PF as a photosensitizer which influences the bacterial genomes and its
      possible practical use, is discussed.

PMID- 8759153
TI  - A study of induced genotoxicity in MCF-7 cells.
AB  - Following upon earlier work the response of MCF-7 breast cancer cells to
      mitomycin C, a known genotoxicant, was examined. This previous research has
      yielded a baseline of chromosome aberrations in human peripheral blood
      lymphocytes from which comparisons can now be made. Results of genotoxicity
      testing conducted with the same protocol yielded a significantly increased level
      of chromosome aberrations in MCF-7 cells than in normal human peripheral blood
      lymphocytes. Dose response curves are presented. Although these results need to
      be confirmed and extended, the hypothesis is proposed that the present findings
      are simply another manifestation of the genetic instability inherent in these
      cancer cells. This seems to be the only known published study of breast cancer
      cells addressing this issue using the techniques of cytogenetics.

PMID- 8759154
TI  - The effects of near null magnetic field upon the leucocyte response in rats.
AB  - Wistar rats were kept for 2 and 4 weeks in conditions of near null magnetic
      field. The total serum proteins, lipids and glucides, as well as the leucocyte
      and neutrophil counts showed no significant changes against controls kept in
      natural magnetic field conditions. A significant monocytosis, a decrease in the
      circulating phagocyte count and in the phagocytic activity was noticed in null
      magnetic field. These results suggest that the natural magnetic field
      significantly influences health both on the ground and possibly in cosmic
      conditions.

PMID- 8759155
TI  - Interleukin-1 beta, but not IL-1 alpha, stimulates cell proliferation in the
      adrenal cortex.
AB  - Endocrine and immune systems are closely interconnected, so the effect of
      interleukin-1 on adrenal cortex proliferation in vivo was investigated.
      Interleukin-1 alpha (IL-1 alpha) and IL-1 beta (0.1, 1 and 10 micrograms/kg) were
      given twice daily alone or in combination with interleukin-1 receptor-antibody
      (IL-1rAb) to adult male Wistar rats. The cell proliferation ratio was measured by
      5-bromo-2'-deoxyuridine (BrdU) incorporation. BrdU-positive cells were counted in
      entire equatorial sections of the gland, and, in addition, separately for each
      adrenocortical zone. IL-1 beta (1 and 10 micrograms/kg) enhanced cell growth in
      the adrenal cortex. This was due to the stimulation of cell proliferation in the
      zona glomerulosa and fasciculata. IL-1rAb exerted an opposite effect, and
      reversed the stimulatory influence of IL-1 beta. IL-1 alpha did not evoke any
      significant changes in the proliferation ratio of the adrenocortical cells. The
      results indicate a close interconnection between the immune and endocrine systems
      with IL-1 beta providing a growth-promoting stimulus to adrenocortical cells.

PMID- 8759156
TI  - Improved synthesis and characterisation of a hydrazide derivative of
      diethylenetriaminepentaacetic acid for site-specific labelling of monoclonal
      antibodies with 111In.
AB  - The monohydrazide derivative of diethylenetriaminepentaacetic acid,
      (HOOCCH2)2NCH2CH2N(CH2CO-OH)CH2CH2N(CH2COOH++ +)(CH2CO.NHNH2), is a bifunctional
      chelator designed for attaching the radiometal 111In selectively to the
      carbohydrate side chains of pre-oxidised monoclonal antibodies. A simple
      synthesis of this chelator (from diethylenetriaminepentaacetic acid cyclic
      anhydride and hydrazine), and its purification and chemical characterisation, are
      described. Rabbit IgG was oxidised with periodate, and the aldehyde groups thus
      generated were reacted with the linker forming a conjugate that was readily
      labelled in high yield and purity with 111In.

PMID- 8759157
TI  - Direct radioiodination of metabolic 8-hydroxy-quinolyl-glucuronide, as a
      potential anti-cancer drug.
AB  - 8-Hydroxy-quinolyl-glucuronide (8-HOQ-Glu) can be deglucuronidated by the beta
      glucoronidase enzyme, which has an activity that is considerably high in certain
      kinds of cancer cell. Owing to this enzyme activity, 8-HOQ-Glu can be considered
      as a potential anti-cancer drug. The combination of the radiotoxicity known of
      125I nuclide with the cytotoxicity of 8-hydroxy-quinoline (8-HOQ) and
      particularly the selective carrying of 125I into the cancer cells is the
      principal aim of this study. As a first step, the metabolic 8-HOQ-Glu was
      extracted from the urine of rabbits treated with 8-HOQ directly radioiodinated
      using the iodogen method. The results showed that the radioiodination was
      successfully realized, and its yield was found to be about 90-95%.

PMID- 8759158
TI  - Gross alpha-particle activities in the ground waters in Western Anatolia.
AB  - The purpose of this study is to present data on gross alpha-particle activity, pH
      and conductivity in the ground waters in Western Anatolia. The gross alpha
      particle activities in 27 ground water samples were determined by radiochemical
      carrier-precipitation methods. The gross alpha-particle activities of water
      samples were measured by using a ZnS (Ag) detector system. Measurable alpha
      particle activity is present in all ground water samples, with one ground water
      sample having a gross alpha-particle activity > 0.55 Bq/L.

PMID- 8759159
TI  - Anti-HIV triterpene acids from Geum japonicum.
AB  - The methanol extract from the whole plant of Geum japonicum was found to inhibit
      the human immunodeficiency virus (HIV-1) protease. Through bioassay-directed
      fractionation of the extract, a new triterpene acid along with five known
      triterpene acids, ursolic acid, epipomolic acid, maslinic acid, euscaphic acid,
      and tormentic acid, were isolated. The structure of the new compound was
      determined by spectral means including 1H-1H COSY, HMQC, HMBC, and NOE
      experiments to be 2 alpha, 19 alpha-dihydroxy-3-oxo-12-ursen-28-oic acid (1). Of
      these compounds, 1, ursolic acid, and maslinic acid showed potent inhibitory
      activity against HIV-1 protease.

PMID- 8759160
TI  - Cyclopentabenzofuran lignan protein synthesis inhibitors from Aglaia odorata.
AB  - In the course of screening for Ras function inhibitors, rocaglaol (1) and the
      related compounds, the known pyrimidinone (2) and the novel aglaiastatin (3),
      were isolated from a CHCI3 extract of the leaves of Aglaia odorata. The structure
      of 3 was elucidated as a novel cyclopentabenzofuran on the basis of its NMR
      spectroscopic data and by X-ray crystallographic analysis. These compounds (1-3)
      were potent inhibitors of the growth of K-ras-NRK cells, with IC50 values of 1-10
      ng/mL, and induced normal morphology in K-ras-NRK cells at 10-30 ng/mL. They also
      specifically inhibited protein synthesis. Aglaiastatin (3) was slightly more
      potent than 1 and 2 in inhibiting cell growth. Aglaiastatin (3) reduced the
      amount of Ras, possibly by inhibiting its de novo synthesis.

PMID- 8759161
TI  - Lupane derivatives from Lophopetalum wallichii with farnesyl protein transferase
      inhibitory activity.
AB  - Chloroform-soluble extracts of the stems and of the mixed stems and stem bark of
      Lophopetalum wallichii were found to be inhibitory in a farnesyl protein
      transferase (FPTase) bioassay system. During the course of activity-guided
      fractionation, the known lupane-type triterpenes, ochraceolide A (1),
      ochraceolide B (2), betulin, and lupeol and the new lupane lactone, dihydro
      ochraceolide A (4), were isolated. The stereochemistry of the epoxide group of
      ochraceolide B (2) was determined by preparation of both epoxide isomers [2, and
      the new semisynthetic derivative, 20-epi-ochraceolide B (3)] from 1. The
      structure of 4 was established by reduction of 1 with sodium borohydride.
      Compounds 1 and 2 exhibited significant inhibitory activity in the FPTase assay
      (IC50 values of 1.0 and 0.7 microgram/mL, respectively). Lupeol was found to be
      weakly active (IC50 65.0 micrograms/mL) in this test system, whereas no
      significant inhibition was detected for betulin or compounds 3 or 4. When
      evaluated against a panel of human cancer cells in culture, compounds 1 and 4
      were modestly cytotoxic. Compounds 2 and 3 were not active in the panel.

PMID- 8759162
TI  - Ehretianone, a novel quinonoid xanthene from Ehretia buxifolia with antisnake
      venom activity.
AB  - Ehretianone (1), a new quinonoid xanthene, together with known sterols, was
      isolated from a MeOH extract of the root bark of Ehretia buxifolia. The structure
      of ehretianone was elucidated as 7-hydroxy-9a alpha-(3-methylbut-2-enyl)-4a
      alpha,9 alpha-(2-methylprop-2-enyl)-4a, 9a-dihydro-1,4-dioxoxanthene on the basis
      of spectroscopic data and X-ray crystallographic analysis. The antisnake venom
      activity of ehretianone against Echis carinatus venom in mice is also reported.

PMID- 8759163
TI  - Antibacterial neoclerodane diterpenoids from Ajuga lupulina.
AB  - The whole plants of Ajuga lupulina afforded five compounds, including three new
      clerodane diterpenes, lupulins A-C (1-3), whose structures were elucidated by
      spectral methods. Among these compounds, lupulins A (1) and B (2) as well as the
      acid hydrolysate (5) of lupulin D (4) showed antibacterial activities against
      Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli.

PMID- 8759164
TI  - Antiplatelet flavonoids from seeds of Psoralea corylifolia.
AB  - The MeOH extract of the seeds of Psoralea corylifolia L. was found to inhibit the
      aggregation of rabbit platelets induced by arachidonic acid, collagen, and
      platelet activating factor. Bioassay-directed fractionation led to the isolation
      of three flavonoids, isobavachalcone (1), neobavaiso-flavone (2), and bavachin
      (3). Compounds 1 and 2 inhibited platelet aggregation.

PMID- 8759165
TI  - Mucronine J a 14-membered cyclopeptide alkaloid from Zizyphus mucronata.
AB  - From the CH2Cl2 extract of the root bark of Z. mucronata (Rhamnaceae), a new
      cyclopeptide alkaloid, named mucronine J, was isolated together with previously
      known alkaloids abyssenine A and mucronine D. The structure of mucronine J was
      elucided by mass spectrometry and 1D and 2D NMR. A solution conformation is
      proposed on the basis of NOE experiments in combination with MM2 calculations.

PMID- 8759166
TI  - Two new quassinoids, ailantinols A and B, and related compounds from Ailanthus
      altissima.

PMID- 8759167
TI  - A new norcembranoid dimer from the red sea soft coral Sinularia gardineri.
AB  - A study of Sinularia gardineri (Pratt) (Alcyoniidae), collected in the Red Sea,
      revealed a new heptacyclic norcembranoid dimer singardin (1). The structure of
      singardin was deduced by spectroscopic analysis. A known sesquiterpene,
      guaianediol (2), and the known cembranolides (1R,5S,8R,10S,11R)-11-hydroxy-1
      isoprenyl-8-methyl-3,6-dioxo -5,8-epoxycyclotetradec-12-ene 10,12-carbolactone (5
      epi-sinuleptolide) and sinuleptolide were also isolated. Compounds 1 and 2 show
      cytotoxicity to murine leukemia (P-388), human lung carcinoma (A-549), human
      colon carcinoma (HT-29), and human melanoma cells (MEL-28).

PMID- 8759168
TI  - Extraction and quantitation of digoxin and acetyldigoxin from the Digitalis
      lanata leaf via near-supercritical methanol-modified carbon dioxide.
AB  - An extraction process is reported that employs a near-supercritical mixture of
      CO2 and MeOH to extract the cardiac glycoside, digoxin, from the Digitalis lanata
      leaf. The method development of the sample preparation procedure is presented in
      detail, and reasons for trends that occur in the natural products extraction are
      given.

PMID- 8759169
TI  - New prenylated quinones from Peperomia galioides.
AB  - Two new prenylated quinones, piperogalone (1) and galopiperone (2), and a new
      prenylated dihydroquinone, hydropiperone (3), were isolated from Peperomia
      galioides H.B.K (Piperaceae). Hydropiperone exhibited potent antiparasitic
      activity against three species of Leishmania.

PMID- 8759170
TI  - DNA topoisomerase I inhibitors: cytotoxic flavones from Lethedon tannaensis.
AB  - From ethyl acetate and methanolic extracts of Lethedon tannaensis leaves, which
      were cytotoxic against murine leukemia (P-388) and human nasopharynx carcinoma
      (KB) cells, one new and six known 5-hydroxy-7-methoxyflavones variously
      substituted on the B ring were isolated and their structures determined by
      spectral analysis. Compounds active against KB cells were velutin (4) (IC50 4.8
      microM), 7,3',5'-tri-O-methyltricetin (2) (IC50 22.2 microM), genkwanin (6) (IC50
      30.6 microM), and the novel compound, 7,3',4'-tri-O-methyltricetin, named
      lethedocin (1) (IC50 47.6 microM). These flavones required the presence of
      hydroxyl groups at C-5 and C-4' and methoxyl groups at C-7 and C-3' for
      inhibition of calf thymus DNA topoisomerase I activity.

PMID- 8759171
TI  - Lycaconitine revisited: partial synthesis and neuronal nicotinic acetylcholine
      receptor affinities.
AB  - The norditerpenoid alkaloid lycaconitine (2) was synthesized from lycoctonine (3)
      and its affinity determined for two neuronal nicotinic acetylcholine receptor
      subtypes. The structure of 2 was confirmed by a combination of spectroscopic
      methods.

PMID- 8759173
TI  - Hormone replacement therapy and diabetes mellitus.

PMID- 8759172
TI  - Antimalarial activity: the search for marine-derived natural products with
      selective antimalarial activity.
AB  - In this short review, an approach to the isolation of potential antimalarial
      agents and lead compounds is outlined. A discussion of organism collection,
      followed by a description of biological testing and isolation methodologies, is
      also given. For two organisms, details of their secondary metabolite chemistry
      are reported. From one of these, Laurencia papillosa, the two aromatic compounds
      p-hydroxybenzaldehyde (1) and p-methoxybenzyl alcohol (2) were isolated. From the
      other, the tropical marine sponge Cymbastela hooperi, 15 diterpenes (3-17), which
      contain isonitrile, isothiocyanate, and isocyanate functionalities, are reported.
      Together with the diterpenes, three sesquiterpene hydrocarbons, 18-20, and the
      thiol, 21, were obtained. All structures were established by spectroscopic
      methods, particularly 1H-1H and 1H-13C shift-correlated 2D NMR spectroscopy and
      accurate mass measurement (HREIMS). The majority of isolates demonstrate
      significant and selective in vitro antimalarial activity. For compounds 4-17 a
      brief description of their possible structure-activity relationships is provided.

PMID- 8759174
TI  - TSH receptor and disease.

PMID- 8759175
TI  - Thyroid autoimmune disorders in patients with chronic hepatitis C before and
      during interferon-alpha therapy.
AB  - BACKGROUND AND AIMS: Hepatitis C virus is involved in the induction of
      autoimmunity and interferon can also induce hepatic and non-hepatic autoimmune
      reactions. This study assessed the prevalence of thyroid autoantibodies and
      autoimmune thyroid disorders in patients with chronic hepatitis C before and
      during interferon therapy. PATIENTS AND METHODS: We studied prospectively 207
      patients positive for anti-HCV and viral RNA. One hundred and forty-four of them
      received a therapeutic trial of one year with interferon-alpha. Free thyroxine,
      TSH and autoantibodies to thyroglobulin and thyroid microsomes were
      systematically tested at entry and at weeks 12 and 24 in both untreated and
      treated patients. RESULTS: Sixteen of the 207 patients (7.7%) had thyroid
      dysfunction, including positive antithyroid antibodies in 14 (6.7%) and
      hypothyroidism in 10 (4.8%) prior to interferon therapy. In addition, during
      pretreatment evaluation one patient developed clinical hyperthyroidism after
      transient subclinical hypothyroidism and another had subclinical hyperthyroidism.
      Prevalences of positive antithyroid antibodies and hypothyroidism were
      significantly higher in women (14.7 and 10.5%, respectively, vs 0% in men, P <
      0.01) and were directly associated with increasing age (P < 0.01). The incidence
      of thyroid dysfunction was also significantly higher in patients with other
      autoantibodies such as anti-nuclear (ANA) (P < 0.01). A trial with interferon was
      initiated in 144 patients and 8 of 142 (5.6%) without previous thyroid
      abnormalities developed thyroid dysfunction, including positive antithyroid
      antibodies in 7 (4.9%) and hypothyroidism in 4 (2.8%) with a prevalence again
      significantly higher in women (12.7 and 8.3%, respectively, vs 1% in men, P <
      0.01) and also directly related to increasing age (P < 0.01). An association was
      found between the development of thyroid dysfunction during interferon therapy
      and the presence of other autoantibodies, including ANA, anti-DNA and anti
      Sjogren's antibodies (P < 0.01), as well as with the induction of autoimmune
      hepatitis and Sjogren's syndrome (P < 0.01 and < 0.05 respectively). Thyroid
      abnormalities were reversed in all patients when interferon therapy was
      discontinued. CONCLUSIONS: No significant association was found between chronic
      hepatitis C and the presence of thyroid autoimmunity in female patients. On the
      contrary, interferon therapy induced antithyroid autoantibodies and thyroid
      dysfunction de novo in patients with chronic hepatitis C without pre-existing
      thyroid abnormalities. Thyroid dysfunction secondary to interferon was reversible
      after discontinuation of therapy.

PMID- 8759176
TI  - Effect of thyroid substitution on hypercholesterolaemia in patients with
      subclinical hypothyroidism: a reanalysis of intervention studies.
AB  - OBJECTIVE: The significance of mild hypercholesterolaemia in subclinical
      hypothyroidism and whether there is beneficial reduction after thyroxine
      replacement, remain controversial. We aimed to describe the association between
      hypercholesterolaemia and subclinical hypothyroidism, and to quantify the effect
      of thyroid substitution therapy by an analysis of previously published
      intervention studies. DATA SOURCES: Intervention studies cited in the Medline
      database from January 1976 until January 1995, with index terms cholesterol,
      hypercholesterolaemia, hyperlipidaemia, thyrotrophin (TSH), hypothyroidism,
      thyroid and human. A total of 148 studies were reviewed. DATA EXTRACTION: We
      recorded the year of publication, study design, number of patients enrolled, mean
      age, duration of thyroid substitution, normal range of TSH levels, TSH levels pre
      and post-substitution treatment and total cholesterol in plasma before and after
      treatment. DATA ANALYSIS: (1) Qualitative description of studies on the
      relationship between hypercholesterolaemia and hypothyroidism, both subclinical
      and clinical. (2) Precision weighted pooled estimates of the effect of thyroid
      substitution therapy on the plasma levels of total cholesterol, in patients with
      subclinical and overt hypothyroidism. RESULTS: Subclinical hypothyroidism was two
      to three times more frequent in people with an elevated total plasma cholesterol.
      In addition, the total plasma cholesterol levels were slightly elevated in
      patients with subclinical dysfunction of the thyroid. Thyroid substitution
      therapy in patients with subclinical hypothyroidism, restoring the TSH levels to
      normal, decreased total cholesterol by 0.4 mmol/l (95% confidence interval (Cl)
      0.2-0.6 mmol/l) independently of the initial plasma level. The effect of thyroid
      substitution therapy on HDL-cholesterol in patients with subclinical
      hypothyroidism was not consistent. The effect of thyroid substitution in patients
      with overt hypothyroidism was highly dependent on the pretreatment levels of
      total cholesterol. In these patients substitution therapy decreased total
      cholesterol by 1.2 mmol/l (95% Cl 0.9-1.5 mmol/l) when the plasma levels were
      elevated up to 8 mmol/l, and by 3.4 mmol/l (95% Cl 3.0-3.7) when plasma levels
      were higher than 8 mmol/l. The high density lipoprotein (HDL)-cholesterol level
      decreased and amounted to 0.16 mmol/l (95% Cl 0.07-0.24). CONCLUSIONS: Thyroid
      substitution treatment in patients with hypercholesterolaemia and subclinical
      hypothyroidism decreases total plasma cholesterol by 0.4 mmol/l, but plasma
      levels remain elevated in most patients. Further treatment with dietary
      restriction and cholesterol synthesis inhibitors should then be considered.

PMID- 8759177
TI  - Time-related effects of a progestogen on the isoforms of serum gonadotrophins in
      17 beta-oestradiol treated post-menopausal women.
AB  - OBJECTIVE: It has previously been shown that 17 beta-oestradiol (E2) implants
      counteract the formation of more acidic isoforms of the gonadotrophins in post
      menopausal women. A much lesser effect was observed on the charge of the
      gonadotrophin isoforms in women with chronic oral daily therapy with 2 mg E2
      combined with a progestogen, 1 mg norethisterone acetate (NETA), in spite of
      similar serum levels of E2 and SHBG. The presence of the progestogen in the
      latter study may explain the difference observed. The present study investigated
      the effect of the progestogen NETA on the charge and concentration of serum FSH
      and LH in E2 implant treated women. DESIGN: A group of 8 post-menopausal women,
      mean age 65 years (range 50-80 years) treated with 20 mg E2 implants every 6
      months, participated in the study. The women were given a daily oral medication
      of 5 mg NETA for a 4-week period starting at 4 weeks after the insertion of an E2
      implant (mean serum E2 420 pmol/l). This treatment with NETA was repeated in 6 of
      the women starting at 18 weeks after the insertion of the E2 implant (mean serum
      E2 317 pmol/l). Blood samples were obtained at the start of the NETA therapy,
      after 2 and 4 weeks of treatment and at 4 weeks after the last NETA treatment.
      The effects of NETA therapy on the charge of the serum gonadotrophin isoforms was
      determined by electrophoresis in 0.1% agarose suspension and FSH, LH, E2, and
      SHBG were determined with fluoroimmunoassays. RESULTS: The NETA treatment
      decreased the serum FSH and LH levels after 2 weeks to 24 and 23% of the levels
      before NETA and after 4 weeks to 14.6 and 8.8%, which were 1.3 and 2.2% of the
      mean levels for non-treated post-menopausal women. Both FSH and LH isoforms
      became more acidic during the first 2 weeks of treatment. During the following 2
      weeks of NETA treatment the isoforms of both FSH and LH became more basic again.
      Ten weeks later both the concentration and the charge of the gonadotrophins were
      similar to those before the NETA treatment. The changes in concentration and
      charge of the gonadotrophins during the second treatment period were similar to
      those during the first. All the changes were statistically significant (P < 0.05 
      < 0.001). The mean SHBG level decreased (P < 0.01) from 84.5 to 70.6 nmol/l
      after 2 weeks and to 59.9 nmol/l after 4 weeks of NETA treatment and increased (P
      < 0.01) 10 weeks later to 77 nmol/l. CONCLUSION: In the oestradiol treated women,
      the effect of the progestogen norethisterone acetate on the charge of the
      gonadotrophin isoforms was time-related. The oestradiol effect on the charge was
      counteracted during the first 2 weeks of progestogen treatment and more acidic
      isoforms appeared in the circulation. During the following 2 weeks the isoforms
      became more basic again. The levels of the gonadotrophins were efficiently
      decreased after 2 weeks of progestogen treatment and further decreased after 4
      weeks. The time-related effect of the progestogen on the gonadotrophin isoforms
      may be mediated via changes in the pattern of GnRH release from the hypothalamus.
      The observed gradual decrease in the SHBG level during the progestogen therapy
      may cause an increased oestradiol effect on the hypothalamus and pituitary.

PMID- 8759178
TI  - Three years of GH treatment in Turner's syndrome: complex effect of GH dosage on
      growth parameters. French Pediatric Clinics and Sanofi-Winthrop.
AB  - OBJECTIVE: There have been few studies of GH dose responses in Turner's syndrome.
      We have therefore compared the growth effect of two doses of subcutaneous GH:
      0.45 (D1) or 0.90 (D2) IU/kg/week. DESIGN: Multicentre study with two parallel
      randomized groups treated with D1 or D2 dose for one year, then with D2 for the
      second and third years in both groups. PATIENTS: Ninety-seven girls with Turner's
      syndrome aged from 4.8 to 16.5 years. RESULTS: The first mean height velocity
      (HV) was significantly higher with D2. At one year the girls changed from D1 to
      D2 showed a further acceleration in HV. During second and third years HV remained
      above the mean for untreated Turner girls, in both groups. Mean cumulative height
      gains over the 3 years were 1.06 and 1.17 SDS/CA (Ranke's Turner standard) in
      groups G1 and G2 respectively. Bone maturation, over 36 months, was 33.7 (G1) and
      31.9 (G2) months. CONCLUSION: These results suggest that, if a higher initial GH
      dose is associated with a greater net initial height gain, the duration of
      treatment might affect the long-term results. Intermittent treatment should be
      considered.

PMID- 8759179
TI  - Growth hormone-binding protein related immunoreactivity is regulated by the
      degree of insulinopenia in diabetes mellitus.
AB  - OBJECTIVE: Derangements in the GH/IGF axis are common in patients with diabetes
      mellitus. In insulin-dependent diabetes mellitus (IDDM), these disturbances seem
      to be due to a partial defect in GH action on its own receptor or via a post
      receptor defect. In non-insulin-dependent diabetes mellitus (NIDDM), data are
      limited, and the regulation of the GH receptor (GHR) remains unclear. However,
      animal studies with diabetic rats demonstrated that the GHR density may be
      influenced by insulin disposal at the hepatocyte. With respect to this hypothesis
      we studied the relation between peripheral insulin status and the serum GH
      binding protein (GHBP), which reflects indirectly the GHR density in the tissues.
      Patients with IDDM were compared to a NIDDM group as well as to a group of
      healthy subjects. DESIGN AND PATIENTS: Basal blood samples for the determination
      of serum GHBP, GH, and IGF-I were obtained from patients with IDDM (n = 27),
      subjects with NIDDM (n = 112) and healthy controle (n = 42). Insulin, proinsulin,
      C-peptide and IGF-binding protein 1 (IGFBP-1) serum levels were used to estimate
      the insulin status in diabetic patients. RESULTS: GHBP serum levels were
      significantly lower in patients with IDDM than in either NIDDM or controls (P <
      0.001). Conversely, the IGF-I levels were reduced in both groups of diabetics. A
      subgroup of hypoinsulinaemic NIDDM patients showed significantly decreased GHBP
      concentrations (P < 0.05) compared to the NIDDM sub-group with hyperinsulinaemia.
      Furthermore, GHBP levels were significantly decreased in insulin-treated patients
      with NIDDM compared to either non-insulin-requiring subjects or normal controls
      (P < 0.05). A significant direct relation was found between levels of GHBP and
      total insulin dose (P < 0.01) in patients with IDDM. In the NIDDM group, GHBP was
      correlated with proinsulin (P < 0.001), C-peptide (P < 0.01), Insulin (P < 0.05)
      and inversely with IGFBP-1 (P < 0.001). Multiple linear regression analysis
      indicated a significant contribution of proinsulin and IGFBP-1 to the variation
      of GHBP. CONCLUSIONS: Decreased GHBP levels in IDDM as well as in NIDDM correlate
      with insulinopenia. Since the degree of insulinopenia depends on the capability
      of the beta-cells to secrete proinsulin, C-peptide and insulin, we hypothesize
      that these hormones at least partially influence the serum level of GHBP. Low
      GHBP levels may reflect a reduced GH receptor density and a concomitant GH
      insensitivity, which leads to an impaired IGF generation in insulin-deficient
      patients.

PMID- 8759180
TI  - Predicting the growth response to growth hormone in patients with intrauterine
      growth retardation.
AB  - OBJECTIVE: Human GH treatment of short children who had intrauterine growth
      retardation (IUGR) results in a highly variable growth response. The object of
      this study was to test the hypothesis that differences in responsiveness to
      exogenously administered GH might reflect differences in endogenous GH secretion
      or sensitivity. DESIGN: Prospective study evaluating th growth response to GH
      therapy in short individuals with prior IUGR. PATIENTS: Ten short, prepubertal
      children with prior IUGR were studied. Mean age was 6 years (3.39-8.61). Mean
      bone age was 4.6 years (2.3-8.3). Mean body mass index was 13.2 kg/m2 (9.9-14.0;
      normal 13.5-19.0). MEASUREMENTS: Overnight spontaneous GH release was measured
      using a constant withdrawal pump and stimulated GH release was measured following
      clonidine (0.15 mg/m2) administration. IGF-I concentrations were measured at
      baseline and 12, 24, 36 and 48 hours after sequential doses of GH (0.05 and 0.2
      mg/kg/dose) given 48 hours apart. Patients were treated with GH (0.125 mg/kg
      three times a week) and growth response was assessed. In the second and third
      year, attempts were made to improve the growth rate by nutritional
      supplementation and increasing the dose of GH to 0.25 mg/kg three times a week.
      RESULTS: All patients had normal integrated nocturnal GH secretion (> 3
      micrograms/l, 6mU/l) and normal peak GH secretion in response to clonidine (> 7
      micrograms/l). In the first year of the trial, mean growth velocity (GV)
      increased from 5.39 cm/year +/- 0.29 to 7.32 cm/year +/- 0.39 (P = 0.004).
      Changes in GV correlated inversely with integrated GH (r = -0.69; P = 0.038),
      baseline IGF-I concentration (r = -0.88; P = 0.002) and baseline GV-SDS (r = 
      0.68; P = 0.043). There was no correlation between change in GV and GH binding
      protein, baseline height SDS or age. The effect of GH waned in the second year,
      but tended to remain greater than the pretreatment growth rate (6.54 +/- 0.49 vs
      5.53 cm/year +/- 0.29; P = 0.09). No significant advancement of bone age over
      chronological age was observed over the first 2 years. Increasing nutritional
      intake by 17% did not result in significant weight gain nor increase in height
      velocity. Doubling the dose of GH in the second or third year did not result in a
      significant increase in GV. CONCLUSION: The variable response to GH therapy in
      short children with a history of intrauterine growth retardation may partly
      reflect relative sufficiency or insufficiency of GH. Baseline IGF-I levels and
      baseline growth velocity appear to be useful and practical predictors of response
      to GH.

PMID- 8759182
TI  - Accelerated bone loss in post-menopausal women with mild primary
      hyperparathyroidism.
AB  - OBJECTIVES: Osteopenia is regarded as an indication for parathyroidectomy in
      primary hyperparathyroidism. However, uncertainty exists as to the extent and
      degree of the skeletal effects in those with mild disease. We sought to determine
      whether mild primary hyperparathyroidism affects the rate of bone loss in
      postmenopausal women. DESIGN: Prospective 2-year comparison of rates of bone loss
      throughout the skeleton in 17 post-menopausal women with untreated mild
      asymptomatic primary hyperparathyroidism, and 48 age-matched, eucalcaemic
      controls. RESULTS: The women with primary hyperparathyroidism had a greater
      annual rate of loss of bone mineral density (BMD) of the total body (mean +/- SE,
      primary hyperparathyroidism -1.15 +/- 0.31%, controls -0.39 +/- 0.10%; P = 0.04)
      and its spine subregion (primary hyperparathyroidism -2.08 +/- 0.88%, controls
      0.04 +/- 0.35%; P = 0.02). Lumbar spine BMD tended to decline in the primary
      hyperparathyroidism group (-0.35 +/- 0.33%) in contrast to the control group
      (+0.28 +/- 0.22%) (P = 0.10). There were no significant differences between the
      groups in rates of changes of BMD in the legs or the proximal femur. In the
      primary hyperparathyroidism group, the rate of total body bone loss in the eight
      women known at study entry to have had long-standing (> 5 years) primary
      hyperparathyroidism was -1.52 +/- 0.61%/year, similar to that of the whole group.
      CONCLUSION: Primary hyperparathyroidism is associated with an increased rate of
      loss of total body bone mineral density in post-menopausal women. Prolonged
      disease duration is therefore likely to be associated with an increasing risk of
      osteopenia, such that skeletal surveillance and interventions designed to reduce
      bone loss should be considered.

PMID- 8759181
TI  - Acute biochemical effects of growth hormone treatment compared with conventional
      treatment in familial hypophosphataemic rickets.
AB  - OBJECTIVE: Conventional treatment of familial hypophosphaiaemic rickets with oral
      phosphate and 1 alpha-hydroxycholecalciferol (1 alpha HCC) does not
      satisfactorily correct the metabolic or physical defects of the disease and can
      have adverse effects, such as nephrocalcinosis. Hyperoxaluria from increased oral
      phosphate intake may contribute to nephrocalcinosis. Growth hormone enhances
      renal tubular phosphate reabsorption and 1,25-dihydroxy-cholecalciferol
      production in normal and in GH deficient individuals, and may thus be of benefit
      to patients with familial hypophosphataemic rickets. PATIENTS: We have assessed
      the acute effects of GH on phosphate and calcium metabolism in 6 children (age 4
      14 years) with familial hypophosphataemic rickets. DESIGN: Each patient served as
      his/her own control and received the following in a sequential non-randomized
      design: conventional treatment with oral phosphate 1.0-3.4 mmol/kg/day in 3-6
      divided doses and 1 alpha HCC 18-31 ng/kg/day-no treatment-GH 0.05 mg/kg daily-GH
      and 1 alpha HCC-and GH with phosphate and 1 alpha HCC. Each treatment was given
      for 7 days with 7 day periods of no treatment in between. MEASUREMENTS AND
      RESULTS: Glomerular filtration rate, tubular maximum rate of phosphate
      reabsorption per litre of glomerular filtrate (TmP/GFR) and serum 1,25
      dihydroxycholecalciferol increased with GH. Mean 24-hour plasma phosphate
      concentrations did not increase with GH but were higher in the treatment phases
      which included phosphate and 1 alpha HCC (P = 0.002). Serum PTH was higher when
      GH was given in combination with phosphate and 1 alpha HCC compared to other
      phases. Urine oxalate excretion did not differ between the treatment phases.
      CONCLUSIONS: GH seemed to partially correct the defects in renal tubular
      phosphate transport and 1 alpha-hydroxylation of 25-hydroxycholecalciferol. We
      speculate that the net effect of GH treatment was an increase in body phosphate,
      although this was not reflected in a change in plasma phosphate. Therefore, GH in
      combination with 1 alpha HCC may act as a phosphate sparing agent, permitting
      treatment with lower and less frequent doses of oral phosphate and reducing
      adverse effects such as nephrocalcinosis.

PMID- 8759183
TI  - Overnight dexamethasone pre-treatment improves the performance of the lysine
      vasopressin test in the diagnosis of Cushing's syndrome.
AB  - OBJECTIVE: There is no endocrine test which is completely reliable for the
      confirmation of Cushing's syndrome and in separation of the various aetiologies.
      We have tested the hypothesis that overnight dexamethasone pre-treatment should
      result in a better performance of the lysine-vasopressin (LVP) test in the
      diagnosis of Cushing's syndrome. STUDY DESIGN AND PATIENTS: We studied 61
      subjects, including 25 pituitary-dependent and 9 pituitary independent Cushing's
      (7 adrenal tumour and 2 ectopic ACTH syndromes), 18 euadrenal controls, 4
      depressed subjects, and 5 cushingoid patients. The subjects received 1 mg of
      dexamethasone orally at 2300 h and the following morning they were given 10 IU of
      lysine-vasopressin im. MEASUREMENTS: Plasma cortisol (RIA) was measured at times 
      15, 0, 15, 30, 45, 60, 75, 90 and 120 minutes. RESULTS: The dexamethasone
      modified LVP (Dx/LVP) test resulted in four patterns of cortisol response. The
      dexa sensitive pattern (positive suppression and negative response to LVP) was
      found in euadrenal subjects; the dexa insensitive pattern (negative suppression
      and positive response to LVP) was seen in Cushing's disease; a non-responsive
      pattern (negative suppression and negative response to LVP) was observed only in
      pituitary independent Cushing's; and an indeterminate pattern (positive
      suppression and positive response to LVP) was equivocal, being observed in 2
      control subjects, 1 patient with Cushing's disease and 1 depressed patient. In
      separating control subjects from Cushing's syndromes the Dx/LVP test had 88.9%
      sensitivity, 100% specificity and 96.2% diagnostic accuracy; when the test was
      used to segregate Cushing's disease from control subjects we found 96.0%
      sensitivity, 100% specificity and 97.7% diagnostic accuracy. The performance
      variables for the Dx/LVP test in separating pituitary dependent from pituitary
      independent Cushing's were uniformly 100%. Depressed and cushingoid subjects did
      not differ from control subjects in their cortisol patterns during the test.
      Successful removal of the pituitary microadenoma in Cushing's disease was
      invariably followed by a reversal of the abnormal cortisol pattern (dexa
      insensitive) during the test to a dexa sensitive pattern indistinguishable from
      that of control subjects. CONCLUSION: These results confirm our hypothesis and
      suggest that an improved performance of any corticotroph stimulus (oCRH, LVP, AVP
      or desmopressin) in the diagnosis of Cushing's syndrome should result from pre
      treatment with dexamethasone.

PMID- 8759184
TI  - The outcome of hypophysectomy for prolactinomas in the era of dopamine agonist
      therapy.
AB  - OBJECTIVE: Dopamine agonists are the primary therapeutic modality for the
      majority of patients with prolactinomas, with pituitary surgery reserved for
      those patients intolerant of or resistant to these agents. Most published
      surgical series, however, contain patients treated by surgery as the primary
      therapeutic modality. Previous exposure to dopamine agonists or the selection of
      patients with prolactinomas resistant to conventional therapy may potentially
      compromise the surgical success rate. The purpose of this study was to evaluate
      the efficacy and safety of pituitary surgery for prolactinomas in a tertiary
      referral centre where the majority of patients were operated on after treatment
      with dopamine agonists. DESIGN: A retrospective review of the outcome of
      pituitary surgery for prolactinomas performed at a tertiary neurosurgical centre
      by a single neurosurgeon. PATIENTS: Twenty-three patients underwent excision of a
      macro and 11 excision of a micro-prolactinoma. MEASUREMENTS: Pituitary tumour
      diameter was determined by CT or MRI imaging. Pre and post-operative measurements
      were made of serum PRL concentration (off dopamine agonist therapy), free T4,
      free T3, LH and testosterone (males). Post-operative restoration of a menstrual
      cycle was taken to indicate resolution of hypogonadism in female patients.
      RESULTS: The majority (73.9%) of the patients with macro and all with micro
      prolactinomas had received dopamine agonists preoperatively. Of the 23 patients
      with macroprolactinomas, in whom the median preoperative PRL concentration was
      13255 mU/l, 17 (73.9%) had radiological evidence of suprasellar extension and 5
      (21.7%) cavernous sinus invasion. Only 4 (17.4%) of the patients with
      macroprolactinomas had a normal serum PRL post-operatively, although there was an
      improvement in visual fields in 66% of those with preoperative defects. The
      median preoperative PRL concentration was 4309 mU/l in the patients with
      microprolactinomas, significantly lower than in the macroprolactinoma group (P =
      0.02). Despite a significant fall in serum PRL postoperatively (median PRL 860
      mU/l, P = 0.0001), only 45.5% of patients had a normal serum PRL concentration
      after surgery. CONCLUSIONS: The cure rate following pituitary surgery for
      prolactinomas in a tertiary referral centre was low when compared with previous
      series in which surgery was used as the primary therapeutic modality. We suggest
      this may result both from dopamine agonist pretreatment and the referral of
      prolactinomas resistant to conventional therapy. The outcome is probably a more
      realistic reflection of the results of pituitary surgery for prolactinomas as
      currently practised in the majority of neuroendocrine centres.

PMID- 8759185
TI  - Pre-clinical Cushing's syndrome: an unexpected frequent cause of poor glycaemic
      control in obese diabetic patients.
AB  - OBJECTIVE: Autonomous cortisol secretion without clinical stigmata of Cushing's
      syndrome (CS) has been recently recognized and termed pre-clinical or sub
      clinical CS. The common assumption is that CS is an extremely rare cause of
      uncontrolled diabetes; however, the prevalence of this entity has not been
      studied. We assessed the prevalence of pre-clinical CS among obese patients with
      uncontrolled diabetes. PATIENTS AND DESIGN: (1) In a retrospective analysis, the
      medical records of 63 patients with endogenous CS were reviewed. (2) In a cross
      sectional study, 90 obese patients (BMI > 25 kg/m2) followed in a University
      Hospital and the local Health Fund endocrine and diabetes clinics, with poorly
      controlled diabetes (glycosylated haemoglobin > 9%), underwent an overnight 1 mg
      dexamethasone suppression. In patients with non-suppressible cortisol levels (>
      140 nmol/l), Liddle's 2 and 8 mg dexamethasone suppression tests and imaging
      studies were performed. MEASUREMENTS: The prevalence of poorly controlled
      diabetes, the major presenting symptom of CS, was assessed in the retrospective
      analysis. The prevalence of "true' CS and the false positive rate in the
      overnight dexamethasone suppression test were calculated. The endocrine
      evaluation of the patients with pre-clinical CS and the effects of surgical cure
      on glycaemic control are described. RESULTS: In the retrospective analysis, 11
      (17.5%) had diabetes and 2 (3.2%) lacked the classic physical characteristics of
      the syndrome. In the cross-sectional study, 4 patients failed to suppress plasma
      cortisol (< 140 nmol/l). In one patient the diagnosis of CS was not confirmed by
      a standard Liddle's test and was therefore considered false positive. In the
      other 3, the diagnosis of CS was confirmed (prevalence of 3.3%, 95% confidence
      interval 1-9%). In all other patients the overnight cortisol suppression test was
      normal (cortisol level 47.3 +/- 2.5 nmol/l (mean +/- SEM)). After surgical
      treatment of CS, glycaemic control was markedly improved in all 5 patients (2
      from retrospective and 3 from cross-sectional studies). CONCLUSIONS: The
      prevalence of pre-clinical Cushing's syndrome in obese patients with poorly
      controlled diabetes appears to be considerably higher than previously believed.
      The overnight dexamethasone suppression test proved to be a simple, sensitive and
      highly specific screening test for Cushing's syndrome despite the presence of
      obesity and hyperglycaemia.

PMID- 8759186
TI  - An ovarian lipid cell tumour causing virilization and Cushing's syndrome.
AB  - We report a 73-year-old woman with rapidly developing symptoms and signs of
      Cushing's syndrome and high urinary free cortisol. She was virilized and hirsute
      with testosterone levels which became exceptionally high. ACTH was suppressed and
      CT scan of the adrenals and pelvis showed no abnormality. Ultrasound scanning
      showed enlargement of the left ovary. Venous catheter studies suggested a left
      ovarian source. A 2-cm diameter lipid cell tumor was removed from the left ovary
      laparoscopically. Histology was initially benign, and clinical and biochemical
      cure of Cushing's syndrome was rapid. However, the neoplastic nature of the
      ovarian tumour was demonstrated 12 months later when peritoneal metastases were
      detected and there was then clinical and biochemical relapse.

PMID- 8759187
TI  - Non-islet cell tumour-associated hypoglycaemia: 111In-octreotide imaging and
      efficacy of octreotide, growth hormone and glucocorticosteroids.
AB  - A patient presented with frequent episodes of spontaneous hypoglycaemia due to a
      solitary fibrous tumour of pleural origin, secreting incompletely processed pro
      insulin-like growth factor II (big IGF-II). Somatostatin receptors were
      demonstrated in the tumour by 111 inlabelled octreotide scintigraphy, but despite
      maximal doses of octreotide, there was no suppression of big IGF-II secretion and
      the hypoglycaemia persisted. The combination of GH and glucocorticoid therapy
      abolished the hypoglycaemia.

PMID- 8759188
TI  - Dexamethasone-suppressible adrenal tumour in untreated 21-hydroxylase deficiency.

PMID- 8759189
TI  - Growth hormone replacement treatment in adult patients.

PMID- 8759190
TI  - T-cell receptor gene analysis in cutaneous T-cell lymphomas.
AB  - An essential property of the immune system is its ability to generate diverse
      antibody and T-cell mediated responses to virtually any potential foreign
      particle. The basic molecular mechanisms responsible for producing this extensive
      diversity have now been elucidated. Each T cell expresses a unique membrane bound
      T-cell antigen receptor (TCR) which combines with specific antigenic peptides and
      major histocompatibility complex molecules. The characterization of TCR usage now
      represents a focal point for many studies of inflammatory and neoplastic
      disorders. Such studies are helping to clarify the pathogenesis of T-cell
      mediated diseases and provide the basis for the development of specific
      therapies. This paper will review several techniques used to identify neoplastic
      T-cell clones in cutaneous T-cell lymphoma. Similar methods may be used to
      analyse TCR gene usage in cutaneous inflammatory dermatoses.

PMID- 8759191
TI  - Port wine stains on the lower limb: response to pulsed dye laser therapy.
AB  - The pulsed tunable dye laser is the established treatment for facial port wine
      stains (PWSs), particularly in children. There have been very few studies
      specifically addressing the efficacy of this laser in the treatment of lower limb
      PWSs. Twenty-seven patients with lower limb PWSs have been treated with the
      Candela pulsed tunable dye laser. Seventeen patients have been discharged; one
      patient had greater than 95% clearance of the naevus and three others had a good
      response to treatment. Ten patients who are continuing treatment have had an
      average of 9.4 treatments. Only one patient has achieved a good result, and none
      an excellent result. These results are disappointing compared with published
      figures for outcome following pulsed tunable dye laser treatment to facial PWSs,
      and confirm the clinical impression that PWSs on the lower limb do not respond
      well to pulsed dye laser therapy.

PMID- 8759192
TI  - Failure of pulsed dye laser therapy for resistant verrucae.
AB  - Treatment with the 585-nm pulsed dye laser was performed in seven patients with
      viral warts (six with plantar warts and one with a periungual wart) who had
      failed to respond to conventional therapeutic modalities, including keratolytics,
      formalin soaks, cryotherapy, curettage, CO2 laser and systemic retinoids. Each
      patient was and treated on six occasions, separated by intervals of 3 weeks, with
      fluences of 8.5-9.5 J/cm2. Final follow-up was performed 3 weeks after the final
      treatment. All patients showed some decrease in the thickness of their warts,
      this being of a small degree in five of the patients. In the remaining two, there
      was a moderate reduction in both thickness and wart size. None of the patients
      experienced complete resolution of their lesions. symptomatic improvement was
      obtained in all three patients who had previously complained of pain. These data
      indicate that treatment of resistant viral verrucae of the periungual and plantar
      skin with the pulsed dye laser is not curative although partial resolution and
      symptomatic improvement may occur.

PMID- 8759193
TI  - Nail growth measurement employing nail indentation--an experimental follow-up
      study of nail growth in situ.
AB  - Nail growth was studied over 20 weeks in five healthy volunteers by indenting
      eight nails in each subject with a dental burr. The indentations were drilled in
      the middle part of the lunula with the proximal edge of the indentation 1 mm from
      the cuticle. Their volume was measured by filling them with an elastic two
      component material immediately after indentation and 4, 8, 12, 16 and 20 weeks
      thereafter. Nail growth as reflected by the volume changes of the indentations
      could be followed for 8-12 weeks in the thumb, the middle finger and the second
      toe and for 20 weeks in the big toe. The most rapid outgrowth, 8-12 weeks,
      occurred in the second toe and middle finger. The decrease in the volume of the
      indentations by approximately 30-35%, as they travelled from the lunula towards
      the distal end of the nail plate, also reflects nail growth from the nail bed.
      This study has shown that indentation of the nails and the measurement of their
      volume changes provides a reliable and simple method for the study of nail
      growth.

PMID- 8759194
TI  - Pemphigus vulgaris in distant relatives of two families: association with major
      histocompatibility complex class II genes.
AB  - We describe major histocompatibility complex (MHC) class II gene haplotypes in
      two extended families, each of which has two members with pemphigus vulgaris
      (PV). One family is of Ashkenazi Jewish descent and the other family of English
      Scottish descent. In one family the patients are distant relatives; in the other,
      both share the same mother but have different fathers. The affected relatives in
      the two families have never shared a common environment and live in distant
      states. All four PV patients, regardless of whether they were of Ashkenazi Jewish
      or of English-Scottish descent, had the same haplotype, namely HLA-DRB1 0402,
      DQA1 0301, DQB1 0302. Thus the PV patients, even though distantly related within
      a family, had the same MHC class II haplotype previously documented in Jewish
      patients. This observation further supports the concept that PV may result from
      an enhanced genetic susceptibility or predisposition to the disease.

PMID- 8759195
TI  - Expression of the T-cell activation antigens CD27 and CD28 in normal and
      psoriatic skin.
AB  - Activated T lymphocytes are thought to be involved in the pathogenesis of
      psoriasis. From studies with peripheral blood T lymphocytes it is known that T
      cells show a decrease in membrane expression of CD27 molecules during continuous
      antigenic stimulation. The T-cell activation molecule CD28 is thought to be
      involved in the transduction of an antigen-non-specific costimulatory signal.
      Therefore, in order to elucidate further the pathogenesis of psoriasis we studied
      the expression of CD27 and CD28, together with CD4, CD8 and CD45RA in this benign
      inflammatory dermatological disease. We used immunohistochemical techniques to
      determine absolute numbers of T lymphocytes and expression of these T-cell
      activation and T-subset-specific molecules in normal (n = 7), uninvolved
      perilesional (n = 7) and lesional psoriatic (n = 7) skin. We found that not only
      lesional but also clinically uninvolved perilesional skin showed an increased
      number of T cells. Further, immunohistochemical studies showed that CD27 is
      expressed by a minority of normal skin T cells, while in lesional psoriatic skin,
      expression was even lower, and almost absent in perilesional skin sections. In
      contrast to normal skin, both perilesional and lesional psoriatic skin contained
      no CD28 positive T cells. In lesional psoriatic skin, however, T cells showed
      predominantly the CD4 phenotype, while in perilesional skin CD8 positive T cells
      were dominant. Two conclusions were reached: first, the absolute number of T
      cells, their CD27, CD28 and CD45RA expression, and the influx of CD8 positive T
      cells, indicate that perilesional psoriatic skin is different from normal and
      lesional psoriatic skin; and secondly, the data on CD27 and CD28 suggest that not
      only lesional but also perilesional psoriatic skin is subject to continuous
      antigenic stimulation, thus leading to decreased CD27 and CD28 expression on skin
      T cells.

PMID- 8759196
TI  - Comparison of the actions of kallidin and bradykinin in the skin of normal and
      psoriatic subjects.
AB  - With the recent development of selective drugs acting on the kinin system and the
      identification of a kallikrein-like enzyme from psoriatic blister fluid, there is
      now much interest in the possible role of kinins in psoriasis. We have examined
      the time-course of the inflammatory (weal and flare) responses to intradermal
      kallidin (lysbradykinin) and bradykinin in normal volunteers, and have compared
      the dose-response effect of these agents in normal volunteers and patients with
      psoriasis. Initially, normal subjects (n = 5) received coded intradermal
      injections of 50 microliters normal saline containing kallidin or bradykinin
      (0.1, 0.5, 1.0 and 5.0 micrograms). Weal volume, weal area and flare area were
      calculated at 5, 15, 30 and 60 min by measuring two perpendicular diameters and
      change in skinfold thickness. Weal and flare measurements were subsequently made
      at 15 and 5 min, respectively. Patients with psoriasis (n = 9) and normal
      subjects (n = 10) were given intradermal injections of kallidin (0.1 and 1.0
      microgram) and bradykinin (0.1, 0.5 and 1.0 microgram) in clinically normal
      forearm skin, using histamine and normal saline as controls. The dose-response
      effects of kallidin on weal and flare responses in human skin were established in
      the study and compared with those of bradykinin. There was wide inter-individual
      variability for both agents and, although mean responses to the highest doses of
      kallidin and bradykinin were decreased in psoriatic skin, no significant
      differences were found between the psoriatic and normal group for kallidin,
      bradykinin or histamine. Hence, there do not appear to be any obvious altered
      vascular responses to kallidin or bradykinin in patients with psoriasis, despite
      the fact that kinins may be generated in psoriatic tissue.

PMID- 8759197
TI  - Phenytoin-induced toxic epidermal necrolysis: a case report.
AB  - We present a case of phenytoin-induced toxic epidermal necrolysis resulting in 60
      70% skin involvement. Systemic corticosteroids and prophylactic antibiotics used
      initially were discontinued, and subsequent management concentrated on intensive
      supportive treatment. The patient survived, but is left with disabling ocular
      complications.

PMID- 8759198
TI  - Bullous pemphigoid and penicillamine.
AB  - We describe a woman who developed bullous pemphigoid in association with
      penicillamine therapy. While pemphigus is a well-recognized complication of
      penicillamine, pemphigoid should also be considered in the differential diagnosis
      of bullous eruptions induced by this drug.

PMID- 8759199
TI  - Chronic bullous disease of childhood following Epstein-Barr virus seroconversion:
      a case report.
AB  - We report the case of a 3-year-old boy with classical chronic bullous disease of
      childhood (CBDC) arising after recent Epstein-Barr virus seroconversion following
      infectious mononucleosis. The patient also had small red cells and decreased
      levels of circulating IgA. He received combined treatment with dapsone and
      prednisone with good results. Our report is the first of CBDC preceded by Epstein
      Barr virus seroconversion. The virus may have had an initial immunopathogenic
      role in the genesis of the bullous eruption.

PMID- 8759200
TI  - Kaposi's varicelliform eruption in a patient with healing second degree burns.
AB  - A 15-year-old boy with Kaposi's varicelliform eruption complicating healing
      second degree burns is reported. Clinically, umbilicated vesicles and pustules
      evolving to extensive erosions appeared over previously burned areas, sparing
      normal skin. Rapid diagnosis was made on the basis of the presence of
      multinucleate giant cells in a Tzanck smear. Therapy with intravenous acyclovir
      was followed by complete epithelialization without scarring. Previous cases of
      Kaposi's varicelliform eruption in burned patients are reviewed.

PMID- 8759201
TI  - The clinical significance of partial lipoatrophy and C3 hypocomplementaemia: a
      report of two cases.
AB  - Partial lipoatrophy often presents with a characteristic 'cadaveric' facial
      appearance but may also present with manifestations of immune deficiency and
      renal disease. We present two cases illustrating all these features.

PMID- 8759202
TI  - Cutis laxa complicating Ehlers-Danlos syndrome type II.

PMID- 8759203
TI  - Strict anatomical coexistence of vitiligo and psoriasis vulgaris--a Koebner
      phenomenon?
AB  - We describe a patient who developed typical psoriatic plaques covering completely
      or partly the vitiliginous areas of her skin. Her psoriasis was strictly limited
      to the vitiliginous patches with no involvement of the normal skin. Strict
      anatomical coexistence of both diseases is extremely rare and suggests a causal
      mechanism, possibly due to a Koebner phenomenon, but genetic and environmental
      factors may also be involved.

PMID- 8759204
TI  - Secondary amyloidosis complicating arthropathic psoriasis.
AB  - We report a patient with secondary systemic amyloidosis complicating arthropathic
      psoriasis. At autopsy amyloidosis was observed in the spleen, kidneys, liver,
      gastro-intestinal tract, lung, heart, pancreas, adrenal glands, thyroid and gall
      bladder in addition to the skin by histological, histochemical and
      ultrastructural studies. The amyloid deposits in these organs were of amyloid A
      protein type.

PMID- 8759205
TI  - Cutaneous xanthomatous tumours as an expression of chronic myelomonocytic
      leukaemia?
AB  - Nonspecific cutaneous xanthomas have been reported in a variety of lymphocytic
      neoplastic processes, but to date only three cases of xanthomatous lesions
      associated with monocytic leukaemias have been described. We now report a patient
      with a chronic myelomonocytic leukaemia (CMML) associated with these lesions. The
      clinical and immunohistochemical features do not correspond to any entity
      previously described and suggest that xanthomas is are a cutaneous expression of
      the CMML.

PMID- 8759206
TI  - Demodex folliculitis on the trunk of a patient with mycosis fungoides.
AB  - A 43-year-old man with tumour stage mycosis fungoides developed multiple
      follicular pustules on the trunk during total-skin electron beam therapy. A
      potassium hydroxide preparation of the contents of the pustules revealed the
      presence of Demodex mites. The patient was treated with 6% sulphur lotion with
      rapid improvement of the cutaneous lesions. We believe that this case represents
      a pustular folliculitis caused by Demodex mites. Immunosuppression associated
      with mycosis fungoides and its treatment may have resulted in the proliferation
      of this obligate parasite of the pilosebaceous follicle, and the development of
      the folliculitis.

PMID- 8759207
TI  - Scrotal pyoderma gangrenosum associated with dermatomyositis.
AB  - Pyoderma gangrenosum (PG) of the scrotum is extremely rare. We report a case of
      scrotal PG associated with dermatomyositis. Initial healing was slow despite the
      use of oral prednisolone and azathioprine. Healing was accelerated by the local
      use of a potent topical corticosteroid. PG should be considered in the
      differential diagnosis of ulcerating lesions of the genitalia.

PMID- 8759208
TI  - Scalp necrosis in temporal (giant cell) arteritis:implications for the
      dermatologic surgeon.
AB  - Temporal arteritis, a variant of giant cell arteritis, is a systemic
      granulomatous vasculitis of large and medium-sized arteries. Usually the clinical
      features are dominated by ophthalmological and neurological complications. In
      rare instances, ischaemic necrosis, especially of the scalp, may lead patients to
      the dermatologist. We report a 76-year-old woman presenting with a unilateral
      scalp necrosis, accompanied by a dramatic ipsilateral impairment of vision.
      Immediately after duplex-sonography of the extracranial vessels and after
      initiation of corticosteroid therapy, the diagnosis of temporal arteritis was
      confirmed by temporal artery biopsy. One month later, because of insufficient
      secondary healing of the ulcer, the defect was covered by a mesh graft. The
      taking of the graft was delayed due to immunosuppressive therapy, but was
      complete. The patient unfortunately died as a result of complications related to
      surgical removal of an aspergilloma in the sphenoid cavity secondary to
      immunosuppressive therapy. We discuss the technique of artery biopsy and the
      possibility of surgical management of scalp necrosis in temporal arteritis.

PMID- 8759209
TI  - Acquired progressive lymphangioma occurring following femoral arteriography.
AB  - Our case report concerns an unusual case of acquired progressive lymphangioma
      (APL) which developed in a 52-year-old Japanese man following femoral artery
      catheterization for angiography. The histological examination revealed many
      irregularly shaped and dilated lymphatic channels that were lined by a single
      layer of endothelial cells. Immunohistochemical staining for von Willebrand
      factor was negative in the endothelial cells of the dilated channels. Electron
      microscopic study demonstrated no Weibel-Palade bodies in the cytoplasm of the
      endothelial cells. The endothelial cells had no distinct basement membrane.

PMID- 8759210
TI  - Tumoral calcinosis: an unusual cause of cutaneous calcification.
AB  - Tumoral calcinosis is an uncommon ectopic calcification syndrome characterized
      clinically by the presence of irregular, painless, periarticular soft tissue
      calcifying masses, and pathologically by fibrous-walled cystic spaces containing
      structureless calcific debris and associated with a variable inflammatory
      reaction. The pathogenesis remains obscure but the condition probably represents
      a disordered tissue reparative process. Of the previous literature reports,
      almost all have been in patients of African origin. We report a case in a white
      English woman.

PMID- 8759211
TI  - A case of giant bathing trunk naevus with neurofibroma-like change.
AB  - It is recognized that cells of melanocytic naevi may resemble neuroid structures
      and the term neurotization has been used to describe this phenomenon. This may
      result in difficulty in the histological differentiation between naevi and
      neurofibromas. We report the case of a patient with a giant bathing trunk naevus
      which has undergone marked neurotization and in whom there had been diagnostic
      difficulty.

PMID- 8759212
TI  - Multiple endocrine neoplasia type 1 presenting as rosacea.
AB  - We present a case of malignant carcinoid initially diagnosed as rosacea. This
      patient was later found to have an additional functioning parathyroid tumour.
      Although a pituitary tumour was not identified, the association represents a
      probable case of multiple endocrine neoplasia type 1 (MEN 1). This autosomal
      dominant syndrome is characterized by tumours of the pancreas, parathyroid and
      pituitary. Inoperable carcinoid tumour is best treated with a long-acting
      somatostatin analogue, octreotide. A diagnosis of MEN 1 has important
      connotations for the proband's first-degree relatives, who should be entered into
      an appropriate screening programme.

PMID- 8759213
TI  - Striae from DEPO-PROVERA injections.

PMID- 8759214
TI  - Environmental factors influencing rosacea.

PMID- 8759215
TI  - Vitiligo and endocrine disorders.

PMID- 8759216
TI  - Calcified subcutaneous nodule in a heart transplant recipient.

PMID- 8759217
TI  - Atrophoderma of Pasini and Pierini.

PMID- 8759219
TI  - Sweet's syndrome preceding inflammatory bowel disease.

PMID- 8759218
TI  - Varicella zoster virus infection complicating bullous pemphigoid.

PMID- 8759220
TI  - Overture: quare fremuerunt?

PMID- 8759221
TI  - Decision making in the neonatal intensive care environment.
AB  - Consideration as to whether withdrawal of intensive care support might be a more
      appropriate line of action than to continue with full intensive care has become a
      part of the life and death decision making process undertaken in neonatal
      intensive care units. After outlining the moral objectives of delivery of health
      care, the arguments for taking quality of life and its various components into
      account during these deliberations are presented. The circumstances in which the
      appropriateness of continuing care should be considered are highlighted and the
      care options presented. The crucial importance of allowing time for parents to
      come to terms with the situation is emphasised as is the need for giving clear
      guidelines to junior staff over resuscitation issues. Finally, an environment for
      providing optimal family support during the process of withdrawal is suggested.

PMID- 8759222
TI  - General practitioners and voluntary euthanasia.

PMID- 8759223
TI  - . . . and a time to die: the medicine of old age.
AB  - Most deaths in Britain occur in old age, and old people dying have as many
      symptoms as do the young. Management is complicated by diagnostic difficulty, by
      the frequency of mental disorder (sometimes treatable) and of severe disability,
      and by the difficulty in ascertaining patients' feelings. Decisions about the
      management of dying are inevitable, and multifactorial, and views of others may
      be helpful. Cardiopulmonary resuscitation is not indicated if futile, and may or
      may not be wanted by the patient. Withholding or withdrawing life-prolonging
      treatment may be justified if the totality of life gained (length and quality) is
      not justified by the burden of treatment. Decisions are most difficult when the
      prognosis is poor but not definitely fatal. Palliative care is important, not
      only in cancer. Euthanasia is seldom requested at present, and in The Netherlands
      is carried out less in old people than young. It would do little for the most
      serious problems of old age.

PMID- 8759224
TI  - Euthanasia and related ethical issues in dementias of later life with special
      reference to Alzheimer's disease.
AB  - Increased public interest and concern regarding euthanasia have been aroused in
      recent years by a number of developments. A succession of judgments pronounced by
      Courts of Law in different parts of the world have, in recent years, sanctioned
      the withdrawal of life sustaining procedures in cases of prolonged and
      irreversible unconsciousness and in patients suffering from painful and
      distressing terminal diseases. They have, therefore, pronounced euthanasia in
      these circumstances to be legally and ethically justified. This has generated
      wide ranging debate regarding the ethics of management of those judged beyond
      hope of recovery or improvement and near the terminal phase of their lives. The
      practice of euthanasia in The Netherlands, which has been in progress for a
      number of years, has also served to focus the attention of the medical and legal
      professions, and the public at large, upon the ethical, legal and clinical
      aspects of euthanasia. In the majority of patients, life had been terminated on
      request. But in a substantial minority, it had been undertaken on an involuntary
      basis. The scale of the practice of euthanasia in The Netherlands in recent years
      has yielded a vast body of information regarding the moral and practical dilemmas
      posed for doctors, families and society concerning patients who are chronically
      unconscious and ambiguously poised between life and death. As a high proportion
      of those whose lives were terminated were of advanced age, the lessons learned
      are closely relevant for the specific theme of this paper.

PMID- 8759225
TI  - Euthanasia in chronic severe disablement.
AB  - One of the major dilemmas for the clinician caring for people with chronic
      disabling conditions is how to provide not only a good quality of life but also
      the best quality of dying. It is my view that the clinician should provide the
      opportunity for living before giving the opportunity to die. By this I mean that
      the clinician has the responsibility to ensure that efforts have been made to
      improve the quality of life by controlling clinical situations and providing
      psychological and emotional support. Once the decision has been made by patient,
      family and clinical team that it is inappropriate that life should continue, then
      the quality of the dying process should be of the highest standard. The present
      attitude of ending the patient's life by withdrawal of nutrition and fluids is
      highly unsatisfactory, if not inhumane, and the option of euthanasia would be by
      far a more satisfactory solution. In addition, a more satisfactory procedure than
      application to the High Court for a directive on withdrawal of tube feeding needs
      to be found. This method is very stressful for family and staff already in
      distress and is an extremely expensive approach. An independent ethical panel to
      ensure that the decision to end the patient's life is clinically appropriate, is
      being carried out purely for the best interests of the patient and is not
      influenced by the other considerations.

PMID- 8759226
TI  - Euthanasia: the intensive care unit.
AB  - The purpose of intensive care is to provide monitoring and organ support for
      patients with critical illness from which recovery is possible. Despite
      increasing technological and pharmacological sophistication, mortality in
      intensive care units remains high, with significant disability in those who
      survive. Methods of predicting outcome from intensive care have been developed.
      These enable patients to be placed in risk groups, but do not accurately predict
      the outcome of individual patients. That prediction is a clinical judgement based
      on the underlying disease, the number of body systems failing and the length of
      time for which intensive care support has been necessary. Once a decision has
      been made to withhold or withdraw intensive care, the principles of good
      palliative medicine should be employed during what will then be the inevitable
      terminal phase of the illness.

PMID- 8759227
TI  - Palliative medicine: a new specialty changes an old debate.
AB  - The specialty of palliative care, of which palliative medicine is part, has
      developed from hospice care for the dying and aims to meet the various needs of
      those suffering from advanced incurable progressive disease. Specialist
      palliative care is not expensive and can be made available to all those who need
      it, at home, in hospital or in a hospice. Arguments in favour of permitting
      euthanasia for those dying as a result of a chronic disease are usually based on
      compassion respect for autonomy or perceived hypocrisy in existing medical
      practice. Each of these arguments is examined and found wanting.

PMID- 8759228
TI  - Euthanasia: the institutional response.
AB  - For health institutions, euthanasia represents an increasingly complex but
      increasingly inescapable debate, in which the expectations of health
      professionals have moved away from the declaratory answer in search of greater
      sophistication and clarity. The House of Lords' Committee on Medical Ethics drew
      attention to the unavoidable complexity of future medical decisions at the end of
      life, the inexorably changing doctor-patient relationship and the demographic
      shift resulting in greater numbers surviving longer to face chronic, degenerative
      conditions. The committee proved a watershed in many respects, not least in the
      moral debate it triggered in the public and among health professionals. Arguably
      it aired questions which still have not been conclusively answered. Its
      questioning mirrored the trend observable among the institutions' membership for
      rigour and detail to justify the positions adopted. It represents one facet of
      the pressure on health institutions, whose previous mode of dealing with the
      euthanasia debate was by declaration and some would say by pontification. Their
      reticence to probe deeper was undoubtedly based partly on the conviction that
      detailed debate about euthanasia was an anathema within professional groups
      committed to the traditional life-preserving goal of medicine. Also influential
      has been the assumption that it would be otiose for professional bodies to issue
      guidance on matters unambiguously covered by law. Arguably, both of these views
      should have been challenged if not dispelled by the effort involved in
      contributing evidence to the House of Lords' Committee. That exercise exposed the
      need for guidance and the ambiguities at law but it remains to be seen how the
      debate will be taken forward, or not, by health institutions.

PMID- 8759229
TI  - Euthanasia and the law.
AB  - This paper examines why the law concerns itself with euthanasia. The nature of
      the right to life and its protection in law is explored. Such a right demands
      legal intervention to prohibit, or at least control, involuntary and non
      voluntary euthanasia. Voluntary euthanasia is not a violation of the individual's
      right to life as such, so on what grounds can law limit autonomy by prohibiting
      such conduct? It is suggested that, while concepts of sanctity of life still play
      a part in the legal debate, fears of abuse in any scheme for voluntary euthanasia
      largely explain the reluctance of many jurisdictions to follow the example of The
      Netherlands. Finally, the paper asks whether reform and regulation of voluntary
      euthanasia are as attractive options as they are sometimes portrayed.

PMID- 8759230
TI  - Euthanasia: law and practice in The Netherlands.
AB  - In The Netherlands, euthanasia is defined as the deliberate termination of the
      life of a person on his request by another person. Although, in this limited
      sense, euthanasia is only one of the issues raised by medical decision-making at
      the end of life, it is, in particular, the acceptance of euthanasia in this
      country that has attracted attention from abroad. Also, in The Netherlands
      itself, the toleration of the courts of euthanasia (if carried out by a physician
      under strict conditions) has given rise to much debate. This contribution surveys
      the developments in the law (including recent legislation), and in medical
      practice, and explores the relation between the two, with particular attention to
      the position of the physician.

PMID- 8759231
TI  - Euthanasia: the law in the United Kingdom.
AB  - The regulation of euthanasia by the criminal law has tended to be one of the more
      contentious areas of medical law, and continues to be the subject of debate. Few
      areas of the criminal law have been so consistently the target of reformist
      pressure, and certainly few areas have so strongly resisted change.
      Understandably, legislators are unwilling to involve themselves in a matter of
      law reform which engenders such moral disagreement, and it is significant that
      only two jurisdictions-The Netherlands and the Australian Northern Territories
      have made any substantial change in their legal practice in this area. In other
      countries, including the UK, the courts and legislators have consistently refused
      to remove the fundamental criminal law objection to the practice of euthanasia.
      This is not to say, of course, that the courts have failed to recognise the
      medical subtleties in medical treatment at the end of life; in several important
      decisions, the courts in Britain have considered the boundaries of the criminal
      law's protection of life and have offered guidelines for doctors facing the
      delicate issues associated with treating the dying patient. Yet, in spite of
      several helpful decisions from the courts, the basic principle remains firm: the
      criminal law does not countenance the taking of life, no matter how good the
      motive. This means that there are very clear legal limits to the extent to which
      doctors can follow their individual consciences in this area.

PMID- 8759232
TI  - Towards the right to be killed? Treatment refusal, assisted suicide and
      euthanasia in the United States and Canada.
AB  - This chapter describes some dominant trends of American and Canadian law in
      relation to treatment refusal, physician-assisted suicide and euthanasia.
      Although common law in both countries recognizes the right of patients to refuse
      treatment, problems have arisen, especially in the US, over treatment refusal on
      behalf of incompetent patients. One response has been to enact advance-directive
      legislation, promoting the use of living wills and proxy appointments. Courts
      have also specified criteria for withholding and withdrawing treatment from
      incompetent patients. The notion of a "right to die', developed in court cases on
      treatment refusal, is now being invoked to support the legalization of assisted
      suicide. Courts are generally reluctant to recognize an extention of this right.
      Debates and court cases following the recent initiative to legalize assisted
      suicide in Oregon and the Sue Rodriguez case in Canada's Supreme Court, which
      resulted in a special report of a Canadian Senate Committee, are of major
      importance for the development of law in this area.

PMID- 8759233
TI  - Killing and letting die: a defensible distinction.
AB  - The distinction between killing and letting die is investigated and clarified. It
      is then argued that in most cases, though not in all, it is worse to kill than to
      let die. In euthanasia the significance of the distinction is diminished, but
      still important.

PMID- 8759234
TI  - Theological perspectives.

PMID- 8759235
TI  - Euthanasia: Buddhist principles.
AB  - Religions provide various forms of motivation for moral action. This chapter
      takes Buddhism as an example from within the Indian "family' of religions and
      seeks to identify the doctrinal and cultural principles on which ethical
      decisions are taken. Although beginning from very different religious premises,
      it is argued that the conclusions to which Buddhism tends are broadly similar to
      those found within mainstream Christianity.

PMID- 8759236
TI  - Euthanasia: sociological perspectives.
AB  - The potential of medicine to intervene to prolong or shorten the life of those
      considered to be dying or of those whose life is rated as of little or even
      negative value has only recently surfaced. It is an issue likely to affect
      society and the normative social relationships which that society believes it is
      duty to promote. It is probable that, covertly, members of the medical profession
      have long played a role in speeding up the process of dying, with or without the
      consent of affected individuals. The openness, however, with which the moral
      issues involved in hastening or prolonging life by medical means are now
      discussed is a late 20th century phenomenon. Sociologists are beginning to study
      the circumstances surrounding the issues and the wider societal implications of
      possible changes in the law, professional practices and normative values. Their
      work may well begin to influence public policy as well as private practice.

PMID- 8759237
TI  - Recent historical perspectives regarding medical euthanasia and physician
      assisted suicide.
AB  - Medical assistance in the termination of life, whether euthanasia or assisted
      suicide, is arguably one of the most hotly debated topics as we approach the
      millenium. While euthanasia has been a subject of controversy for thousands of
      years, the historical influences vis a vis the medical profession are primarily
      rooted in the past century. This chapter seeks to explore some of the recent
      historical developments which have had an impact on the emergence of medical
      euthanasia and physician assisted suicide. The objective is to juxtapose events
      in a way that relates historical fact (and fiction) to current events and
      debates. Sociology, law and theology have each a view and impact in this arena;
      however, they are deliberately left to the side, so as to allow for a
      longitudinal landscape.

PMID- 8759238
TI  - Mechanisms and prevention of restenosis: from experimental models to clinical
      practice.

PMID- 8759239
TI  - Paracrine modulation of heart cell function by endothelial cells.
AB  - An accumulating body of experimental data supports the presence of a paracrine
      pathway for the modulation of myocardial function by cardiac endothelial cells.
      Cardioactive substances released by endothelial cells include nitric oxide,
      endothelin-1, prostanoids, adenylpurines, natriuretic peptides, and other agents
      that have so far only been characterised in bioassay studies. Endothelial cells
      also possess enzymatic activities, in particular ACE/kininase activity, which can
      alter local levels of angiotensin II and bradykinin. Many of the "endothelial"
      mediators can be produced by cardiac myocytes themselves, often under
      pathological conditions, suggesting a potential parallel autocrine pathway.
      Complex reciprocal relationships exist between individual mediators, which affect
      both their release and actions. Most studies to date have focused on the acute
      influence of these agents on contractile function; the longer-term modulation
      both of cardiac structure and function could be equally important. A notable
      feature of the action of several of the endothelial mediators is that they modify
      myocardial contractile behaviour predominantly through changes in myofilament
      properties rather than by altering cytosolic Ca2+ transients. This mode of action
      often results in a disproportionate effect on myocardial relaxation and diastolic
      tone. The opposing contractile effects and differing time-scales of action of
      agents such as nitric oxide and endothelin-1 are reminiscent of the interplay
      between these factors in the regulation of blood vessel tone. The endothelial
      paracrine pathway is likely to act in concert and to interact with other
      cardiovascular regulatory pathways, e.g., the Frank-Starling mechanism,
      neurohumoral influences, the effects of heart rate, coronary perfusion and load.
      A better understanding of its physiological and pathophysiological roles may lead
      to novel therapeutic strategies.

PMID- 8759240
TI  - Hypertension: a case of the gratuitous rider.

PMID- 8759241
TI  - Glucocorticoid-remediable aldosteronism.

PMID- 8759242
TI  - Comparison of in vivo and in vitro haemodynamic function in experimental heart
      failure: use of echocardiography.
AB  - OBJECTIVE: To compare in vivo and in vitro haemodynamic performance in two models
      of experimental cardiac failure. To validate echocardiography as a means of non
      invasive assessment of left ventricular dysfunction in rabbits. METHODS: Cardiac
      failure was induced by doxorubicin injection (1-1.25 mg.kg-1 twice weekly for 8
      weeks (n = 16)) or coronary ligation (n = 12), with 12 controls. Left ventricular
      diastolic dimension and ejection fraction were assessed in vivo by
      echocardiography. The doxorubicin-treated and ligation hearts were subdivided by
      ejection fraction > 0.40 or < or = 0.40 into non-failing and failing groups.
      Thermodilution cardiac output was measured in vivo at baseline and after a fluid
      load. Basal cardiac output and peak cardiac output achieved by increased preload
      were measured in vitro in the working heart mode. RESULTS: The mean ejection
      fractions in the doxorubicin-treated and ligation groups were significantly (P <
      0.001) lower than in controls, but there was wide inter-individual variability
      ranging from normal to severely impaired function [mean +/- s.d. (range) controls
      0.65 +/- 0.03 (0.59-0.72), doxorubicin 0.45 +/- 0.11 (0.30-0.67), ligation 0.42
      +/- 0.12 (0.25-0.65)]. Basal and peak cardiac outputs in vivo and in vitro were
      significantly lower in the doxorubicin and coronary ligation groups than in
      controls, although there was a wider scatter of values in the pathological
      groups. Among the doxorubicin and coronary ligation groups, hearts with ejection
      fractions < or = 0.40 demonstrated significantly impaired haemodynamic function
      compared with those with ejection fractions > 0.40. There were significant
      correlations between ejection fraction and all indices of haemodynamic function
      in vivo and in vitro. CONCLUSIONS: Simple non-invasive measurement of ejection
      fraction allowed improved characterization of haemodynamic responses in vivo and
      in vitro. Individual assessment of animals by echocardiography will improve
      interpretation of cellular or molecular studies in experimental heart failure by
      relating observed abnormalities to the degree of global cardiac dysfunction.

PMID- 8759243
TI  - Right heart failure chronically stimulates heat shock protein 72 in heart and
      liver but not in other tissues.
AB  - OBJECTIVES: During cardiac failure several ontogenically developed adaptional
      mechanisms are activated. Among these, heat-shock proteins (HSP) are expressed in
      response to stress. The aim of the present study was to investigate the HSP72
      protein expression in lungs, liver, cardiac and skeletal muscles during
      congestive heart failure (CHF). METHODS: CHF was induced in Sprague-Dawley rats
      by a single intraperitoneal injection of monocrotaline (50 mg/kg). Two groups of
      animals emerged: a CHF group (n = 10) with right ventricular hypertrophy, pleural
      and peritoneal effusions, and an Hypertrophy group (n = 12) with right
      ventricular hypertrophy without CHF. The data for each group were compared with
      those of control (saline infused) age-matched rats. Lungs, liver, right and left
      ventricles, soleus, extensor digitorum longus and tibialis anterior muscles were
      excised and analyzed for HSP72 concentration by Western blot analysis using a
      specific monoclonal antibody. Noradrenaline levels in the heart were also
      measured using HPLC. RESULTS: The CHF group showed: (1) reduced right (0.460 +/-
      0.090 vs 0.830 +/- 0.070 nmol/ventricle, P < 0.01) and left (1.10 +/- 0.09 vs
      2.10 +/- 0.130 nmol/ventricle, P < 0.001) ventricular content of noradrenaline
      compared to the control; (2) significant activation of HSP72 concentration in
      right and left ventricles (39.4 +/- 1.6 vs 5 +/- 0.9% and 13 +/- 1.2 vs 3.5 +/-
      0.6%, P < 0.001 both) and in the liver (39.8 +/- 11 vs 6 +/- 2%, P < 0.001); (3)
      no modification in HSP72 concentration in lungs and all of the peripheral muscles
      considered. The Hypertrophy group showed: (1) unchanged total noradrenaline
      tissue content as compared to the control; and (2) unmodified HSP72 concentration
      in all tissues analyzed. CONCLUSIONS: The present study demonstrates that CHF,
      but not compensatory hypertrophy, is a specific stimulus for chronic HSP72
      induction in the heart and liver. On the contrary, CHF does not affect HSP in
      lungs and peripheral muscles. HSP 72 induction represents an intracellular marker
      of stress reaction which can persist chronically.

PMID- 8759244
TI  - Role of neutral endopeptidase 24.11 in AV fistular rat model of heart failure.
AB  - OBJECTIVE: The aortovenocaval fistular (AVF) rat represents a model of heart
      failure caused by increased cardiac volume overload and reduced renal function.
      Both circulating vasoconstrictors like the renin-angiotensin-aldosterone system
      and vasodilators like atrial and brain natriuretic peptides (ANP and BNP) are
      activated in this animal model of heart failure. In addition, neutral
      endopeptidase 24.11 (NEP) in plasma and urine is elevated in AVF rats. In the
      present investigation we examined the renal and hormonal effects of the NEP
      inhibitor, ecadotril, in acute and chronic studies in rats with an aortovenocaval
      fistula (AVF). METHODS: Sprague Dawley rats (350-430 g) were prepared by
      introducing a shunt between abdominal aorta and the vena cava. RESULTS: Acute
      administration of the neutral endopeptidase inhibitor, ecadotril (30 mg/kg p.o.),
      significantly improved the reduced renal excretion of sodium in AVF rats (83 +/-
      10 to 145 +/- 14 mumol/kg/h, P < 0.01) but had no significant effect in sham
      operated rats. However, neutral endopeptidase activity in urine was significantly
      decreased after ecadotril in both groups. Plasma ANP was increased after
      ecadotril only in AVF rats (275 +/- 83 to 748 +/- 187 pg/ml, P < 0.05), whereas
      the increase in plasma BNP was not statistically significant. After 4 weeks of
      observation the ANP and BNP plasma levels, renin activity (PRA), angiotensin I,
      and neutral endopeptidase activity were significantly higher in AVF rats than in
      sham-operated rats. Four weeks on ecadotril (30 mg/kg p.o., b.i.d.) increased
      plasma ANP (245 +/- 48 as opposed to 450 +/- 77 pg/ml, P < 0.05) and decreased
      PRA (11.3 +/- 1.5 as opposed to 6.8 +/- 1.2 ng/ml/h, P < 0.005) in AVF rats.
      Plasma NEP activity was inhibited in both groups. Ventricle weight was
      significantly higher in AVF rats than in sham-operated controls, and ecadotril
      treatment over 4 weeks decreased ventricular hypertrophy to a slight extent.
      CONCLUSION: These results indicate that in the AVF rat model of heart failure the
      neutral endopeptidase inhibitor, ecadotril, improves the reduced kidney function
      in AVF rats by raising natriuretic peptides in plasma and probably in urine. NEP
      inhibition with ecadotril could therefore offer useful therapeutic possibilities
      in the treatment of heart failure.

PMID- 8759245
TI  - Increasing coronary perfusion pressure on diastolic and systolic performance is
      less pronounced in right ventricle than in left ventricle.
AB  - OBJECTIVE: Little is known as to whether an increase in coronary perfusion
      pressure can alter the right ventricular (RV) distensibility and the contractile
      function as it does in the case of the LV. METHODS: In eight isolated
      isovolumically contracting canine hearts, RV and LV volumes and coronary
      perfusion were independently controlled. Effects of an increase in coronary
      perfusion pressure (from 73 +/- 1 to 152 +/- 6 mmHg) on the end-diastolic and end
      systolic pressure-volume relations in both RV and LV were assessed. RESULTS:
      Following an increase in coronary perfusion, and at a similar volume of the
      ventricles, end-diastolic pressure was elevated by 2.8 +/- 0.8 mmHg in RV and 8.9
      +/- 2.0 mmHg in LV (P < 0.01; RV vs LV), and the slope of RV end-systolic
      pressure-volume relation, Ees, increased by 11 +/- 6% (P < 0.05) and that of the
      LV Ees by 21 +/- 5% (P < 0.01). The percent change of RV pressure-volume area
      (PVA) was less than that in LV-PVA (26 +/- 9 vs 48 +/- 11%; P < 0.05).
      CONCLUSIONS: Accordingly, increases in coronary perfusion pressure and/or flow
      decreased the RV distensibility and enhanced the RV contractile function, the
      extent of which, however, was less than that in the LV.

PMID- 8759246
TI  - The effect of afterload and angiotensin II on proto-oncogene mRNA levels in the
      isolated working rat heart.
AB  - OBJECTIVES: The proto-oncogenes c-fos, c-myc and H-ras have been shown to rise in
      a characteristic pattern in the left ventricle undergoing hypertrophy in the
      coarctation model of experimental hypertension and there is some evidence to
      suggest that they might play a role in the initiation of hypertrophic growth.
      However, in vivo studies do not discriminate between the direct effects of
      pressure and pressure-independent trophic stimuli such as angiotensin II. To
      examine these influences separately we studied isolated working hearts exposed to
      different afterloads in the presence or absence of angiotensin II. METHODS:
      Hearts from normotensive female Wistar rats were perfused with a modified Krebs
      Henseleit solution, with and without angiotensin II (100 nmol/1) and exposed to
      low (60 mmHg) or high (140 mmHg) afterload (n > 17/group). Proto-oncogene mRNA
      induction in the left ventricle was assessed by Northern blot analysis. RESULTS:
      Aortic pressures were 101 +/- 14/63 +/- 6 mmHg (mean +/- s.d.) with low and 175
      +/- 13/93 +/- 20 mmHg with high afterload; hearts in both groups maintained a
      stable cardiac output over 240 min, except for high afterload hearts not perfused
      with angiotensin II, which showed a 59% drop by the end of the experiment (P <
      0.001). There was a 50% (32%, 72%) (geometric mean and 95% confidence interval)
      increase of c-myc and 54% (27%, 86%) increase in c-fos, but a 32% (25%, 40%)
      suppression of H-ras with high (140 mmHg) as compared with low (60 mmHg)
      afterloads (P < 0.0001 for each). There was no significant difference in c-myc
      and c-fos induction with different levels of high afterload (110, 120, 140 mmHg),
      but for H-ras suppression progressively increased with increasing afterload (P =
      0.003). At high afterload, levels of c-fos rose at 30 min and peaked at 60 min, c
      myc continued to rise up to 240 min, and H-ras was suppressed at all four time
      points. The addition of angiotensin II (100 nmol/l) to the perfusate resulted in
      18% (6%, 28%; P = 0.006) lower c-myc levels, 12% (-6%, 28%; P = 0.18) lower c-fos
      levels and an 11% (-0.1%, 24%; P = 0.056) increase of H-ras. CONCLUSION: The
      isolated perfused working rat heart is capable of performing stably for a period
      of at least 240 min at high afterload pressures comparable to those encountered
      in hypertension. A proto-oncogene induction similar to that seen in the
      hypertrophying heart can be induced by increased pressure alone, without the
      mediating effects of circulating angiotensin II. Hearts perfused with angiotensin
      II showed a more stable performance at high levels of afterload which was
      associated with a minor attenuation of pressure-induced changes in proto-oncogene
      expression.

PMID- 8759247
TI  - Effects of afterload on regional left ventricular torsion.
AB  - OBJECTIVE: To determine if left ventricular torsion, as measured by magnetic
      resonance tissue tagging, is afterload dependent in a canine isolated heart model
      in which neurohumoral responses are absent, and preload is constant. METHODS: In
      ten isolated, blood perfused, ejecting, canine hearts, three afterloads were
      studied, while keeping preload constant: low afterload, high afterload (stroke
      volume reduced by approx. 50% of low afterload), and isovolumic loading (infinite
      afterload). RESULTS: There were significant effects of afterload on both torsion
      (P < 0.05) and circumferential shortening (P < 0.0005). Between low and high
      afterloads, at the anterior region of the endocardium only, where torsion was
      maximal, there was a significant reduction in torsion (15.1 +/- 2.2 degrees to
      7.8 +/- 1.8 degrees, P < 0.05). Between high afterload and isovolumic loading
      there was no significant change in torsion (7.8 +/- 1.8 degrees to 6.2 +/- 1.5
      degrees, P = NS). Circumferential shortening at the anterior endocardium was
      significantly reduced both between low and high afterload (-0.19 +/- 0.02 to 
      0.11 +/- 0.02, P < 0.0005), and also between high afterload and isovolumic
      loading (-0.11 +/- 0.02 to 0.00 +/- 0.02, P < 0.05). Plots of strains with
      respect to end-systolic volume demonstrated a reduction in both torsion and
      shortening with afterload-induced increases in end-systolic volume. Torsion, but
      not circumferential shortening, persisted at isovolumic loading. CONCLUSIONS:
      Maximal regional torsion of the left ventricle is afterload dependent. The
      afterload response of torsion appears related to the effects of afterload on end
      systolic volume.

PMID- 8759248
TI  - Effects of propafenone on the median frequency of ventricular fibrillation in
      Langendorff perfused guinea-pig hearts.
AB  - OBJECTIVE: The aim was to investigate the antifibrillatory effects of two
      concentrations of propafenone by means of signal analysis of epicardial ECG
      recordings in isolated, Langendorff-perfused guinea-pig hearts. METHODS: Isolated
      Langendorff-perfused guinea-pig hearts were used as a model for sustained
      ventricular fibrillation (VF) during reperfusion after global ischaemia. ECG
      signals were recorded for the first 20 min of reperfusion. The recording was
      divided into episodes of 1 s and the median frequency (FM) of the dynamic power
      spectrum was computed for each episode. Cardiac electrical activity was monitored
      for an additional 10 min. Additionally steady state conditions (i.e. constant FM
      values for the remaining observation period) were analysed and the effects of 0.1
      microM and 1.0 microM propafenone added at reperfusion on the FM were examined.
      RESULTS: After initial irregularities, FM remained on a high steady state level
      in the control group. The addition of propafenone altered the steady state value
      of FM in a dose-dependent and significant manner but had no effects on the time
      until steady state was reached. During reperfusion without propafenone, 1 out of
      6 hearts spontaneously converted to a stable sinus rhythm. Reperfusion with 0.1
      microM propafenone caused spontaneous conversion to stable sinus rhythm in 1 out
      of 6 hearts and intermittent periods of sinus rhythms in 2 additional hearts.
      During the first 30 min of reperfusion with 1.0 microM propafenone, 5 out of 6
      hearts spontaneously converted to stable sinus rhythm. The sixth heart showed
      repeated switching between VF and periods of non-sustained sinus rhythm.
      CONCLUSION: Propafenone caused a dose-dependent decrease of FM at steady state
      conditions. The rate of spontaneous termination of VF appeared to be dose
      dependent and the stability of the sinus rhythm was correlated inversely with the
      FM immediately before spontaneous defibrillation. Therefore, in this model the FM
      value prior to spontaneous termination of VF may be useful in the estimation of
      defibrillation success.

PMID- 8759249
TI  - Myocardial calcium-independent phospholipase A2 activity during global ischemia
      in isolated rabbit hearts.
AB  - OBJECTIVES: To study calcium-independent phospholipase A2 activity during global
      ischemia in isolated rabbit hearts by measuring the hydrolysis of the endogenous
      choline phospholipids. METHODS: Langendorff perfused rabbit hearts were exposed
      to global ischemia for 15 or 60 min, or control perfusion for the same length of
      time. The hearts were then rapidly frozen in liquid nitrogen and lyophilized.
      Calcium-independent phospholipase A2 activity in the lyophilized tissue was
      studied by measuring accumulation of lysophospholipids resulting from hydrolysis
      of both the choline diacylphospholipid and the choline plasmalogen pool. RESULTS:
      The calcium-independent phospholipase A2 activity showed the same pH, temperature
      and calcium sensitivity in control and ischemic (15 min of ischemia) lyophilized
      myocardial tissue. Incubation of control and ischemic tissue showed no difference
      in the rate of accumulation of lysophospholipids when the ischemic tissue was
      obtained from hearts exposed to 15 min of ischemia (107 +/- 4 vs 111 +/- 7 nmol/g
      dry wt x min, ischemia versus control, mean +/- s.e.m., n = 8), but a significant
      decrease was noticed in tissue from hearts that had been exposed to 60 min of
      ischemia (31 +/- 9 vs 86 +/- 18 nmol/g dry wt x min, P < 0.05, n = 4). The
      decreased phospholipase A2 activity in tissue exposed to 60 min of ischemia was
      not due to enhanced metabolism of the lysophospholipids (84 +/- 15 vs 79 +/- 8
      nmol/g dry wt x min, n = 4). The calcium-independent phospholipase A2 activity
      was considerably lower in fresh myocardial tissue compared with lyophilized
      tissue, but comparison of control and ischemic fresh tissue gave results
      comparable to those found using lyophilized tissue. The myocardial calcium
      independent phospholipase A2 activity showed no plasmalogen selectivity in either
      control or ischemic myocardium. CONCLUSIONS: In isolated perfused rabbit hearts
      we found no evidence for activation of calcium-independent phospholipase A2
      activity during global ischemia. With prolonged time of ischemia there was a
      significant decrease in calcium-independent phospholipase A2 activity.

PMID- 8759250
TI  - Limitation of myocardial infarct size in the rabbit by ischaemic preconditioning
      is abolished by sodium 5-hydroxydecanoate.
AB  - OBJECTIVE: To investigate the effect of the ATP-sensitive potassium (KATP)
      channel inhibitor sodium 5-hydroxydecanoate (5-HD) on the reduction in myocardial
      infarct size afforded by ischaemic preconditioning in the sodium pentobarbitone
      rabbit. METHODS: New Zealand white rabbits were anaesthetised with sodium
      pentobarbitone and subjected to 60 min occlusion of the first antero-lateral
      branch of the left coronary artery (LAL) followed by 120 min reperfusion.
      Ischaemic preconditioning was achieved by a single episode of 5 min LAL occlusion
      followed by 15 min reperfusion prior to the 60 min occlusion. 5-HD (5 mg kg-1),
      an ischaemia selective KATP channel inhibitor, was administered into the left
      ventricle as a bolus injection 10 min prior to the onset of ischaemic
      preconditioning. Injection of Evans blue dye was used to determine the area of
      the left ventricle at risk and infarct size was determined by incubation of the
      area at risk with nitro-blue tetrazolium. RESULTS: There were no significant
      differences between groups in haemodynamics or area at risk. Ischaemic
      preconditioning resulted in a significant reduction in infarct size (27 +/- 8%)
      when compared to control animals (55 +/- 3%; P < 0.05). Pretreatment of animals
      with 5-HD completely abolished the cardioprotection seen with ischaemic
      preconditioning (50 +/- 6%). CONCLUSION: These results support the hypothesis
      that the cardioprotection afforded by ischaemic preconditioning in the
      pentabarbitone anaesthetised rabbit is dependent on the opening of KATP channels.

PMID- 8759251
TI  - Melatonin prevents ischemia reperfusion injury in hamster cheek pouch
      microcirculation.
AB  - OBJECTIVE: We used the hamster cheek pouch microcirculation to investigate the
      effects of melatonin (ME) on ischemia reperfusion (I-R) injury by in vivo
      microscopy. ME is a hormone produced by the pineal gland and is the most powerful
      and effective hydroxyl radical scavenger detected to date in vitro. The second
      aim was to determine the scavenger effect of ME in cheek pouch microcirculation
      when topically applying an oxygen-derived free radical generating system.
      METHODS: Ischemia was induced by clamping the cheek pouch for 30 min followed by
      30 min of reperfusion. We quantified the increase in permeability, the perfused
      capillary length and leukocyte adhesion by computerized methods. Microcirculation
      was also exposed to a hypoxanthine-xanthine oxidase (H-X) system. RESULTS: In
      control hamsters I-R was associated with increased permeability, increased number
      of leukocytes sticking to venules, and decreased perfused capillary length.
      Treatment with ME completely inhibited microvascular edema formation and reduced
      the number of leukocytes sticking to venules after reperfusion. Moreover, ME
      prevented the marked decrease in perfused capillary length, preserving
      microvascular perfusion. ME topically applied reduced significantly the
      permeability increase due to H-X exposure. CONCLUSIONS: The beneficial effect of
      ME may be related to its antioxidant properties. These protect the endothelial
      barrier integrity as well as preserve microvascular blood perfusion by
      dysfunctions after I-R.

PMID- 8759252
TI  - The vulnerable period for low and high energy T-wave shocks: role of dispersion
      of repolarisation and effect of d-sotalol.
AB  - INTRODUCTION: The induction of ventricular fibrillation (VF) by T-wave shocks has
      been related to dispersion of repolarisation, but only indirect evidence of this
      hypothesis exists. The effects of drugs prolonging repolarisation like d-sotalol
      on the vulnerability to T-wave shocks remain unknown. METHODS: In 9 isolated
      rabbit heart, 7 monophasic action potentials (MAPs) and an ECG were recorded
      simultaneously. Vulnerable periods were determined using two different shock
      strengths, one close to the fibrillation threshold and the other close to the
      upper limit of vulnerability, at baseline and after action potential prolongation
      by d-sotalol. RESULTS: The vulnerable period had a duration of 30 +/- 14 ms for
      the lower and 34 +/- 12 ms for the higher shock strength (P = NS). Coupling
      intervals of the vulnerable periods were 13 +/- 10 ms shorter for higher shock
      strengths as compared to lower shock strengths (P < 0.005). The vulnerable period
      for low shock strengths coincided with dispersion of MAPs at 90% repolarisation
      (r = 0.87-0.92, P < 0.005), and the vulnerable period for high shock strengths
      coincided with dispersion at 70% repolarisation (r = 0.82-0.93, P < 0.005). ECG
      parameters predicted the vulnerable periods less precisely than MAP
      repolarisation (r < or = 0.72). d-Sotalol prolonged MAP durations by an average
      of 33 ms at 70% and 39 ms at 90% repolarisation but did not alter the described
      relations, nor did it reduce dispersion of repolarisation or duration of the
      vulnerable periods. CONCLUSIONS: Dispersion of repolarisation determines
      vulnerable periods and might be part of the arrhythmogenic substrate promoting
      induction of VF by T-wave shocks. The coupling intervals of the vulnerable
      periods depend on the applied shock strength as well as repolarisation, with
      shock strengths close to the fibrillation threshold inducing VF during dispersion
      at 90% repolarisation and shock strengths close to the upper limit of
      vulnerability inducing VF during dispersion at 70% repolarisation. d-Sotalol
      reduces neither vulnerability to T-wave shocks nor dispersion of repolarisation
      in this isolated heart model.

PMID- 8759253
TI  - Differential effects of MS-551 and E-4031 on action potentials and the delayed
      rectifier K+ current in rabbit ventricular myocytes.
AB  - OBJECTIVE: The frequency-dependent effects of MS-551 on the action potential
      duration (APD) and the underlying ionic mechanisms were investigated in
      comparison with those of E-4031. METHODS: Whole-cell clamp techniques were used
      to study action potentials and ionic currents in enzymatically isolated rabbit
      ventricular myocytes. RESULTS: The frequency-response obtained within the range
      of 0.1 to 3.3 Hz was different for MS-551 and E-4031. The APD prolongation by MS
      551 (10 microM) was significant at 0.5-3.3 Hz, whereas that by E-4031 (1 microM)
      was significant at 0.1-1.0 Hz. The prolongation by MS-551 (10 microM) of APD of a
      test action potential, which was preceded by a train of 1.0 Hz stimulation,
      decreased progressively as the rest duration increased, whereas that by E-4031 (1
      microM) remained at the same level. Both MS-551 (10 microM) and E-4031 (1 microM)
      significantly decreased IK, but showed no effects on the transient outward
      current (Ito) and the inward rectifier K+ current (IKl). The development of the
      block on IK and the recovery from the block by MS-551 were voltage dependent. At
      a holding potential of -50 mV, MS-551 reduced the tail current to a similar
      extent (21-34%, n = 6) across all the tested durations of the depolarizing pulses
      to +10 mV, whereas at -75 mV, the intensity of the block progressively increased
      as the durations of depolarizing pulses were prolonged. The recovery from the
      block by MS-551 was absent at -50 mV, but occurred at -75 mV with a time constant
      of 577 +/- 179 ms (n = 6). The development of the block on IK by E-4031 was
      voltage and time independent. No recovery from the block was observed for E-4031
      at either -50 or -75 mV. CONCLUSIONS: These findings suggest that MS-551 produces
      frequency-dependent class III action, presumably due to the voltage-dependent
      binding and unbinding to the IK channels. The reverse frequency dependence of
      class III action by E-4031 cannot be explained by the effects on IK.

PMID- 8759254
TI  - Enhanced modifications of low-density lipoproteins (LDL) by endothelial cells
      from smokers: a possible mechanism of smoking-related atherosclerosis.
AB  - OBJECTIVE: The aim of the study was to investigate LDL modifications by cultured
      human umbilical vein endothelial cells (HUVEC) from women smokers and non
      smokers. METHODS: Modifications of LDL by HUVEC were studied by determining the
      values of thiobarbituric acid-reactive substances (TBARS) and the percentage of
      the most electronegative oxidized LDL fraction (fraction C) by using an ion
      exchange chromatographic method based on fast protein liquid chromatography
      (FPLC). We also studied the cellular production of superoxide anion, the effect
      of various inhibitors and cysteine, and determined total intracellular
      glutathione content and cell growth. RESULTS: LDL exposed to HUVEC from smokers
      for 48 h showed significantly greater modifications than LDL exposed to HUVEC
      from non-smokers, as assessed by TBARS determination (19.4 +/- 1.2, mean +/-
      s.e.m., n = 20 versus 15.4 +/- 0.7 nmol/mg LDL, n = 19; P < 0.01) and by FPLC
      (percentage of fraction C: 39 +/- 7, n = 29 versus 14 +/- 3, n = 34; P < 0.001).
      Moreover, HUVEC from smokers produced significantly more superoxide anion than
      those from non-smokers (0.46 +/- 0.13 nmol/10(5) cell/min, n = 9 versus 0.22 +/-
      0.05, n = 10; P < 0.05). Superoxide production, like cell-induced modification of
      LDL, was strongly dependent on the presence of cysteine in the medium.
      Furthermore, HUVEC from smokers had a significantly (P < 0.05) higher total
      intracellular glutathione content than those from non-smokers (39.9 +/- 3.1
      nmol/mg, n = 9 versus 31.8 +/- 2.2, n = 7). Finally, HUVEC from smokers and non
      smokers showed similar growth at 48 h. CONCLUSION: HUVEC from smokers converted
      significantly more LDL into an atherogenic form than HUVEC from non-smokers, a
      phenomenon that was not due to altered cell growth. HUVEC-mediated LDL
      modifications were strongly thiol-dependent, as both LDL modifications and
      superoxide anion production were inhibited in cysteine-free medium. Stimulation
      of cystine uptake by HUVEC, reflected by the enhanced total glutathione content,
      could account for the enhanced superoxide anion production. All these
      observations may be relevant to the pathophysiology of smoking-related
      cardiovascular disease.

PMID- 8759255
TI  - What is the best primary surgical treatment for the infantile glaucomas?

PMID- 8759256
TI  - The challenge of HIV/AIDS related eye disease.

PMID- 8759257
TI  - Should myopes have routine axial length measurements before retrobulbar or
      peribulbar injections?

PMID- 8759258
TI  - Long-term follow up of primary trabeculectomy for infantile glaucoma.
AB  - BACKGROUND: The treatment for infantile glaucoma is surgical. Treatment options
      include goniotomy, trabeculotomy, combined trabeculotomy-trabeculectomy, and
      trabeculectomy. METHODS: Patients who had a follow up of 5 years or longer after
      primary trabeculectomy were examined to determine the long term stability in
      infantile glaucoma. RESULTS: In eyes with primary infantile glaucoma 92.3%
      achieved control of their glaucoma with a single trabeculectomy; 100% achieved
      control with two trabeculectomies; 85.7% of eyes with secondary infantile
      glaucoma achieved control with a single trabeculectomy. There were no serious
      complications experienced in either group. CONCLUSION: Primary trabeculectomy is
      a safe and successful operation for infantile glaucoma.

PMID- 8759259
TI  - Carcinoma of the conjunctiva and HIV infection in Uganda and Malawi.
AB  - AIM: To investigate the association of human immunodeficiency virus (HIV)
      infection and carcinoma of the conjunctiva in Africa, and the role of human
      papilloma virus type 16 (HPV-16). METHODS: Patients in Uganda and Malawi
      presenting to eye clinics with lesions suspicious of carcinoma were studied.
      Pathological confirmation of eye lesions was sought. HIV testing of patients who
      were biopsied and, in Uganda, of matched case control subjects was carried out as
      was testing of a sample of fixed biopsies for HPV-16 by polymerase chain reaction
      (PCR). The HIV-1 serology, histopathology of conjunctival biopsies (conjunctival
      intraepithelial neoplasia (CIN), invasive carcinoma, other lesions), and
      prevalence of HPV-16 infection were determined. RESULTS: Of Ugandan patients,
      27/38 (71%) with carcinoma (27 invasive carcinoma, 11, CIN) were HIV positive
      compared with 12/76 (16%) of controls (odds ratio 13, 95% confidence interval 5
      38). The calculated population aetiological fraction of carcinoma associated with
      HIV was 66%. Of 32 Malawian patients (20 invasive carcinoma, 12 CIN), 25/29
      tested (86%) were HIV positive. HPV-16 infection was found in 7/20 (35%) of
      carcinoma samples, 0/9 pingueculae, and 2/6 conjunctivitis samples. CONCLUSIONS:
      HIV infection is strongly associated with an apparent increase in the incidence
      of conjunctival carcinoma in Africa. While ultraviolet light is probably the
      prime risk factor and HPV-16 is implicated in a proportion of cases, the
      interactions of ultraviolet light, HIV, HPVs, and other factors are unclear in
      the pathogenesis of carcinoma. The disease represents another model of
      multifactorial epithelial carcinogenesis.

PMID- 8759260
TI  - Optic nerve diameters and perimetric thresholds in idiopathic intracranial
      hypertension.
AB  - AIMS/BACKGROUND: Idiopathic intracranial hypertension (IIH) is a central nervous
      disorder characterised by abnormally increased cerebrospinal fluid (CSF) pressure
      leading to optic nerve compression. An indirect estimate of increased CSF
      pressure can be obtained by the ultrasonographic determination of optic nerve
      sheaths diameters. Computerised static perimetry is regarded as the method of
      choice for monitoring the course of the optic neuropathy in IIH. The aims were to
      compare the echographic optic nerve diameters (ONDs) and the perimetric
      thresholds of patients with IIH with those of age-matched controls, and to
      examine the correlation between these two variables in individual patients with
      papilloedema. METHODS: Standardised A-scan echography of the mid orbital optic
      nerve transverse diameters and automated threshold perimetry (Humphrey 30-2) were
      performed in 20 patients with IIH with variable degree of papilloedema (according
      to the Frisen scheme) and no concomitant ocular diseases. Echographic and
      perimetric results were compared with those obtained from 20 age-matched
      controls. RESULTS: When compared with controls, patients with IIH showed a
      significant increase in mean ONDs and significantly reduced mean perimetric
      sensitivities. In individual patients with papilloedema, the transverse ONDs
      correlated negatively with Humphrey mean deviation values and positively with
      pattern standard deviation values. CONCLUSION: These results indicate that OND
      changes in IIH are associated with perimetric threshold losses, and suggest that
      IIH functional deficits may be related to the degree of distension of optic nerve
      sheaths as a result of an increased CSF pressure.

PMID- 8759261
TI  - Feasibility of automated visual field examination in children between 5 and 8
      years of age.
AB  - AIMS: To investigate how young children develop the ability to undergo a visual
      field evaluation using regular automated perimetry. METHODS: The study included
      42 normal girls aged 5, 6, 7, and 8 years. Twelve locations in the 15 degrees
      eccentricity were tested in one eye, using an Octopus 2000R perimeter with a two
      level strategy. False positive and false negative catch trials were presented.
      The examination was performed three times in succession. Before the examination
      procedure, a specially designed programme was conducted for progressive
      familiarisation. RESULTS: During the familiarisation procedure, it was found that
      all of the 5-year-old children, seven of the 6-year-old children, and three of
      the 7-year-old children were unable to perform immediately, and correctly, the
      instructions given during the familiarisation phase; these children took from 30
      seconds to 3 minutes to comply with the examiner's requests. With the exception
      of one 5-year-old child, all tested subjects completed the planned procedure. The
      mean proportion of false negative answers in catch trials was 1.6%. The mean
      proportion of false positive answers was 12.2%. The quadratic dependency on age
      suggested by the averages was not significant (F(3,116) = 0.88; p = 0.45).
      Detection stimulus improved with age, as shown by the fact that probability of
      perceiving dim stimulus increases significantly (F(3,116) = 12.68; p < 0.0001).
      CONCLUSION: Children did remarkably well regarding both the duration of the
      examination and the reliability of the answers. A preliminary familiarisation
      phase with a specially designed adaptation programme was found to be mandatory
      with children aged 7 or under. To our knowledge, this is the first time that such
      an investigation has been performed.

PMID- 8759262
TI  - Visual field loss following vitrectomy for stage 2 and 3 macular holes.
AB  - AIM: To describe the phenomenon of peripheral field loss following routine pars
      plana vitrectomy for stage 2 and 3 full thickness macular hole and to investigate
      the underlying mechanism. METHODS: Five patients, who reported peripheral field
      defects after apparently uncomplicated vitrectomy, posterior cortical vitreous
      peeling, and perfluoropropane (C3F8) gas tamponade, were studied retrospectively
      with slit-lamp biomicroscopy, automated and kinetic perimetry, fundal fluorescein
      angiography, focal electroretinography (ERG), and colour contrast sensitivity
      (CCS) testing. RESULTS: All five patients, who were between 50 and 73 years of
      age, reported an inferotemporal field defect following resolution of the
      intraocular gas bubble. In all eyes, the scotomata encroached to within 20
      degrees to 30 degrees of fixation and to within 5 degrees to 15 degrees of the
      blind spot. In one eye, a partial altitudinal component was evident. All
      scotomata subsequently remained stable and three eyes developed subtle segmental
      nasal disc pallor and nerve fibre loss corresponding to the field defect. CCS
      testing revealed absent colour contrast in the scotomatous area, in the presence
      of a preserved focal quadrantic flash ERG, compared with normal CCS protan
      thresholds and focal ERGs in unaffected quadrants, indicating preserved outer
      retinal function in the area of the scotoma. CONCLUSIONS: These observations
      support the hypothesis that field defects occur as a result of retinal nerve
      fibre layer damage. It is proposed, on the basis of intraoperative observations
      and other evidence, that the most likely site of nerve fibre damage is at the
      nasal portion of the optic nerve rim or peripapillary retina, probably due to
      traction during cortical vitreous peeling.

PMID- 8759263
TI  - Spatial classification of glaucomatous visual field loss.
AB  - AIMS: To develop and describe an objective classification system for the spatial
      patterns of visual field loss found in glaucoma. METHODS: The 560 Humphrey visual
      field analyser (program 24-2) records were used to train an artificial neural
      network (ANN). The type of network used, a Kohonen self organising feature map
      (SOM), was configured to organise the visual field defects into 25 classes of
      superior visual field loss and 25 classes of inferior visual field loss. Each
      group of 25 classes was arranged in a 5 by 5 map. RESULTS: The SOM successfully
      classified the defects on the basis of the patterns of loss. The maps show a
      continuum of change as one moves across them with early loss at one corner and
      advanced loss at the opposite corner. CONCLUSIONS: ANNs can classify visual field
      data on the basis of the pattern of loss. Once trained the ANN can be used to
      classify longitudinal visual field data which may prove valuable in monitoring
      visual field loss.

PMID- 8759264
TI  - Sublingual timolol--an alternative to topical medication in glaucoma?
AB  - AIMS: To assess whether timolol drops lower a raised intraocular pressure (IOP)
      when given sublingually. This route of administration would be useful for
      glaucoma patients who are unable to instil their own drops--for example, because
      of stroke, poor vision, arthritis, poor coordination, or blepharospasm. METHODS:
      A placebo controlled randomised, double masked, crossover study was undertaken in
      the glaucoma clinic of a large teaching hospital. Twelve patients with ocular
      hypertension with IOPs over 21 mm Hg, normal optic discs, and full visual fields
      were examined by Humphrey perimetry. Single dose units of timolol maleate 0.5%
      drops and normal saline drops were given by instillation in one eye or
      sublingually. The IOP of both eyes, pulse rate, and blood pressure were all
      measured before and after each type of drop and route of administration. RESULTS:
      Two hours after instillation of timolol in one eye, the IOP in the treated eye
      was reduced by a mean of 8.5 mm Hg (p = 0.0000), and by 1.66 mm Hg in the fellow
      eye (p = 0.03). Two hours after sublingual instillation of timolol, the IOP was
      reduced by 7.55 mm Hg in the study eye (p = 0.0000) and by 7.7 mm Hg in the
      fellow eye (p = 0.0000). There was an equal amount of reduction in pulse rate by
      either route, but there was no significant change in blood pressure. CONCLUSIONS:
      The results show that, at least after 2 hours, sublingual treatment is almost as
      effective as topical treatment in lowering a raised IOP.

PMID- 8759265
TI  - Indocyanine green angiographic findings in serpiginous choroidopathy.
AB  - AIMS: Analysis of the choroidal findings in patients affected by serpiginous
      choroidopathy (SC). METHODS: Thirteen patients (23 eyes; 11 males and two
      females; age range 50-68 years; mean age 59.1 years) affected by SC were examined
      with fluorescein angiography (FA) and indocyanine green angiography (ICGA). The
      follow up period was 7-33 months. RESULTS: Using ICGA the disease could be
      divided into the following stages: (1) subclinical or choroidal stage
      (hypofluorescent lesions without FA evidence); (2) active stage (with ICGA and FA
      evidence); (3) subhealing stage (slight late hyperfluorescent lesions with ICGA,
      with no evidence on FA); (4) inactive or healed stage (hypofluorescent areas with
      ICGA and hyperfluorescent areas with FA). CONCLUSIONS: Although FA showed a clear
      distinction between active and healed stages, ICGA allowed a greater subdivision
      of the disease. In particular, ICGA allowed: (1) better staging of SC, revealing
      choroidal alterations when there was no ophthalmoscopic or FA evidence; (2)
      better identification of the active lesions which appear to be larger at the
      choroidal level in comparison with the corresponding retinal lesions; and (3)
      revealed a persistence of choroidal activity even when the signs of retinal
      activity had disappeared. Thus, ICGA should be a particularly useful clinical and
      therapeutic monitoring tool of SC.

PMID- 8759266
TI  - Ultrasound biomicroscopy of eyes undergoing deep sclerectomy with collagen
      implant.
AB  - AIMS: To assess the intraocular pressure (IOP) lowering mechanism of deep
      sclerectomy with collagen implant (DSCI), a non-penetrating glaucoma surgery.
      METHODS: Nine eyes of nine patients with medically uncontrolled open angle
      glaucoma underwent DSCI. Ultrasound biomicroscopy (UBM) of the sclerectomy site
      was performed 1 month after surgery. The following factors were assessed: length
      and height of collagen implant, and thickness of the residual trabeculocorneal
      membrane. RESULTS: Postoperative IOP decreased significantly in all nine eyes
      from a preoperative mean value of 25.8 (SD 4.8) mm Hg to a postoperative (1
      month) mean value of 11.3 (6.3) mm Hg (p = 0.001). In all nine eyes, UBM at 1
      month after surgery showed a subconjunctival filtration through the thin
      trabeculocorneal membrane and through the scleral flap around the collagen
      implant. In four cases, a hypoechoic area in the suprachoroidal space was
      observed and might represent ciliary body detachment or be due to suprachoroidal
      drainage of aqueous humour through the thin deep scleral wall. At 1 month after
      surgery the mean trabeculocorneal membrane thickness was 110.1 (16.8) microns,
      and the mean length and height of the collagen implant were 2.3 (0.1) mm and 1.1
      (0.1) mm respectively. CONCLUSION: DSCI lowered IOP by allowing aqueous
      filtration through a thin trabeculocorneal membrane to the subconjunctival space
      and, eventually, to the suprachoroidal space.

PMID- 8759267
TI  - Role of epithelial hyperplasia in regression following photorefractive
      keratectomy.
AB  - AIM: To determine the relation between epithelial hyperplasia and regression of
      effect after photorefractive keratectomy (PRK). METHODS: Seventy unilaterally
      treated patients with PRK were examined. All eyes had been treated with the
      Summit excimer laser 27 (SD 7) months previously with zone diameters of 4.1 to
      5.0 mm. The untreated fellow eyes served as controls. Epithelial thickness was
      measured centrally with a thin slit optical pachometer and manifest subjective
      refraction was performed. RESULTS: The epithelium was 21% thicker in the treated
      eye (p < 0.0001). The relation between refractive regression and epithelial
      hyperplasia was significant (r = 0.41; p < 0.001). CONCLUSIONS: Epithelial
      hyperplasia after PRK correlated with the myopic shift (including hyperopia
      reduction) after treatment with the Summit laser. A model is proposed suggesting
      that both subepithelial and epithelial layers contribute to regression in the
      Summit treated eyes with 18 microns of epithelial hyperplasia contributing each
      dioptre of regression.

PMID- 8759268
TI  - Sulphapyridine--a new agent for the treatment of ocular cicatricial pemphigoid.
AB  - AIMS: Ocular cicatricial pemphigoid (OCP) is a severe, potentially sight
      threatening systemic disease that sometimes requires systemic immunosuppression.
      This study assessed the clinical outcome of patients with OCP treated with
      sulphapyridine, a sulphonamide with an anti-inflammatory and immunosuppressive
      action but few side effects. METHODS: A prospective, single armed, unmasked
      clinical trial was undertaken at Moorfields Eye Hospital. Twenty consecutive
      patients with moderate or marked conjunctival inflammation due to OCP were
      treated with oral sulphapyridine 500 mg twice daily. The degree of ocular
      inflammation was assessed as nil, mild, moderate, marked, or severe. Success was
      defined as resolution to mild or less. Ocular limbitis, systemic features of the
      disease, and side effects of the drug were also monitored. RESULTS: Follow up was
      a mean of 12.3 (SD 4.0) months and ranged from 7 to 17 months. A successful
      reduction in inflammation was recorded in 22/39 eyes (56%) and 10/20 patients
      (50%). This improvement occurred within 1 month in 64% and in all by 2 months.
      Three patients developed allergy. Other side effects included nausea (n = 3),
      headache (n = 1), urinary hesitancy (n = 1), and mild lymphocytopenia (n = 1).
      These were dose dependent. Progression of cicatrisation was observed in 1/22
      eyes. Success was less likely if there were systemic features of OCP or ocular
      limbitis. CONCLUSIONS: Sulphapyridine was clinically effective in 50% of patients
      with moderate marked inflammation and had few side effects. It is a good
      alternative to dapsone.

PMID- 8759269
TI  - Bell's phenomenon in newborns and premature babies.
AB  - AIMS: To evaluate the development and course of Bell's phenomenon (BP) in
      premature and normal neonates. METHODS: Twenty seven preterm infants and 42
      healthy full term infants were studied. Mean birth weight, gestational age, and
      head circumference were recorded. BP was graded from no response to full
      response. The premature group was examined in the first week of life, and then at
      4 and 8 weeks after birth. The full term group was initially examined at the age
      of 3 days until a full response was observed. RESULTS: No preterm infants
      exhibited BP during the first week of life, while 8/28 (29.6%) exhibited a weak
      to full reflex at 8 weeks of age. In the full term group 15/42 neonates (35.7%)
      demonstrated a mature reflex at age of 3 days and 36/37 (97.3%) at age 16 weeks.
      A significant correlation was observed between BP, sex, and birth weight, as well
      as gestational age in the premature group. No such correlation was found in the
      full term infants. CONCLUSION: BP has a longitudinal course. It is an important
      clinical marker for evaluation and follow up of neuro-ophthalmic maturation in
      neonates.

PMID- 8759270
TI  - Eosinophil cationic protein in tears in allergic conjunctivitis.
AB  - AIMS/BACKGROUND--Eosinophil cationic protein (ECP) is a quantifiable product
      secreted by activated eosinophils. The aim of this study was to assess the degree
      of eosinophil activity in different clinical stages of various forms of allergic
      conjunctivitis. METHODS--Tears were collected in glass capillary tubes from 14
      subjects with seasonal allergic conjunctivitis (SAC), 23 subjects with vernal
      keratoconjunctivitis (VKC), 16 subjects with atopic keratoconjunctivitis (AKC),
      10 subjects with giant papillary conjunctivitis (GPC), and 16 healthy control
      subjects. The samples were analysed in duplicate with a radio-immunoassay for
      ECP. RESULTS--Statistically significant differences were evident between healthy
      controls and allergic subjects (p < 0.001). Subjects with AKC and VKC had
      significantly higher tear ECP values than subjects with GPC and SAC. In addition,
      there was a significant correlation between ECP values and disease severity in
      all disorders. CONCLUSION--The data suggest a particular pathogenic role of the
      eosinophil in VKC and AKC, and a less pronounced but still important eosinophil
      involvement in the disease processes of GPC and SAC.

PMID- 8759271
TI  - Intracellular calcium response to hydraulic pressure in human trabecular cells.
AB  - AIMS: To understand the mechanism for regulation of intraocular pressure, human
      trabecular cells were examined to determine whether they could respond to the
      change in hydraulic pressure. METHODS: Human trabecular cells were cultured from
      trabeculum tissue fragments excised during trabeculectomy in four eyes of three
      patients with primary open angle glaucoma and exposed to the change of hydraulic
      pressure in a tissue culture flask connected to a glass syringe. The pressure was
      exerted by automatic infusion of the piston of the syringe and monitored by a
      pressure gauge. The intracellular calcium concentration was measured in real time
      with a calcium binding fluorescent dye, fluo-3. RESULTS: A small number (about
      10%) of cells appearing morphologically to be trabecular cells showed transient
      elevations or oscillations of the intracellular calcium concentration in response
      to the elevation of hydraulic pressure to 20-30 mm Hg, indicating that a part of
      the human trabecular cells could sense the change in hydraulic pressure.
      CONCLUSION: Some cells in the human trabecular tissue seem to sense the change in
      intraocular pressure and might play a role in its regulation.

PMID- 8759273
TI  - Metachronous lymphoma of the breast and conjunctiva.

PMID- 8759274
TI  - Optic neuropathy associated with hypertrophic cranial pachymeningitis.

PMID- 8759275
TI  - A case of traumatic retinal avulsion at the optic nerve head.

PMID- 8759272
TI  - Ocular oxygen measurement.

PMID- 8759276
TI  - Werner's syndrome.

PMID- 8759277
TI  - Bilateral combined hamartoma of the retina and the retinal pigment epithelium.

PMID- 8759279
TI  - Peters' anomaly.

PMID- 8759278
TI  - The south Asian cataract management study.

PMID- 8759280
TI  - Participation of NH4+ in total ammonia absorption across the rumen epithelium of
      sheep (Ovis aries).
AB  - 1. Participation of NH4+ in total ammonia transport across sheep rumen wall was
      studied in vitro. 2. In Ussing-type chambers addition of NH4+ or K+ to the
      incubation solution on the mucosal side of the epithelium evoked positive short
      circuit currents (ISC). 3. The K+ induced ISC but not the NH4+ induced ISC could
      be blocked by Ba2+ whereas both, K+ or NH4+ induced ISC were blocked by
      quinidine. 4. Transepithelial fluxes of ammonia were significantly reduced when
      quinidine was present in the incubation solution. 5. When the transepithelial
      potential difference was clamped to -25 mV (polarity on the serosal side) ammonia
      fluxes from the mucosal to the serosal side were significantly larger than fluxes
      of ammonia measured as a potential difference of +25 mV. 6. It is suggested that
      NH4+ takes part in ammonia transport across the rumen epithelium, most probably
      by using a K(+)-transport system.

PMID- 8759281
TI  - Intrauterine programming of hypertension in the rat: nutrient interactions.
AB  - The feeding of low protein diets to pregnant rats is known to programme
      hypertension in their offspring though a glucocorticoid-dependent mechanism. To
      establish whether diets of differing fatty acid composition could produce the
      same effects, or modulate the effects of a low protein diet, pregnant rats were
      fed 1 of 4 different diets. Control animals were fed an 18% casein:corn oil (18 +
      Corn) diet, while experimental groups were fed 18% casein:coconut oil (18 +
      Coco), 9% casein:corn oil (9 + Corn) or 9% casein:coconut oil (9 + Coco). Feeding
      of coconut oil diets significantly reduced weight gain of the rats, an effect
      attributable to a lower food intake. Despite this, reproductive performance of
      the rats was not compromised. While pups of the 9 + Corn group were of normal
      birthweight, the dams in the 18 + Coco and 9 + Coco groups gave birth to pups of
      significantly lower weight. At 7 weeks of age male and female pups exposed to the
      9 + Corn diet in utero had significantly elevated systolic blood pressure. Males
      exposed to the 9 + Coco and 18 + Coco diets also had higher blood pressures than
      control animals, but the effect was not observed in females. Female rats exposed
      to the three experimental diets in utero had enlarged hearts, relative to
      controls and the same effect of maternal diet was observed in male rats exposed
      to the 9 + Coco and 18 + Coco diets. Effects of maternal diet upon liver size
      were also noted in males exposed to 18 + Coco and 9 + Corn diets (smaller
      livers). Males exposed to 9 + Corn had smaller lungs than control rats, whilst
      the rats from the 9 + Coco group had significantly enlarged lungs. In rats
      exposed to the 9 + Corn diet in utero there was evidence of increased
      glucocorticoid action in both liver and hypothalamus, where activities of
      corticosteroid inducible enzymes were elevated. There was no evidence of a role
      for glucocorticoids in programming the hypertension of male rats exposed to high
      saturated fat diets in utero. The data would suggest that high saturated fatty
      acid, or low linoleic acid intake in pregnancy may programme hypertension in the
      fetal rat. This effect of maternal diet occurs through a mechanism different to
      that initiated by protein restriction and is sex specific.

PMID- 8759282
TI  - Differential degradation of extracellular adenine nucleotides by folliculated
      oocytes of Xenopus laevis.
AB  - The degradation of extracellular ATP and ADP by Xenopus oocytes was studied to
      investigate whether one or two ecto-enzymes are responsible for breakdown of both
      nucleotides. At a concentration of 100 microM, the half-life of ATP and ADP was
      33 and 40 min, respectively. Degradation of ATP caused an initial fast and then a
      sustained accumulation of ADP in the buffer, while the concentration of AMP in
      the buffer increased slowly, but progressively, in a relatively linear manner.
      The rates of degradation of ATP and ADP were similar at pH levels between 7 and
      10, but the velocity of breakdown of ATP was significantly higher than that of
      ADP at pH of 5-6. In divalent cation-free buffer, the addition of 0.1 mM of Ca2+,
      but not equimolar Mg2+, significantly potentiated the degradation of ATP by
      oocytes while, in the case of ADP, each of these divalent cations were able to
      potentiate its degradation. The rate of hydrolysis of ATP and its kinetic
      constants were not significantly different in the presence or absence of ADP (50
      microM). In conclusion, differences in pH- and cation-dependency, and absence of
      inhibitory effect of ADP on degradation of ATP suggest that degradation of ATP
      and ADP by oocytes is provided by separate enzymes, namely Ca2+/Mg(2+)-dependent
      ecto-ATPase and ecto-ADPase, rather than by one ecto-enzyme.

PMID- 8759283
TI  - Seasonal variations of blood haptoglobin level of brown bears in Japan.
AB  - Haptoglobin (Hp), a hemoglobin-binding protein, is known as an acute phase
      protein increasing in blood during inflammation in most mammals. On the basis of
      our previous studies on purification and characterization of bear Hp (Comp.
      Biochem. Physiol. 110B, 785-789, 1995), in this study, we developed an
      immunoassay method to measure serum Hp level in bear, and measured the
      concentration of Hp in blood samples collected from 84 reared and 25 wild brown
      bears in Hokkaido, Japan. The mean serum Hp concentration was 0.94 +/- 0.25 mg/ml
      in wild bears, which is nearly equal to those reported in other species. In
      reared bears, the Hp concentration was apparently higher (3.82 +/- 0.29 mg/ml),
      although total protein and albumin concentrations were nearly equal in the two
      groups. A significant seasonal variation of serum Hp, low in spring and high in
      autumn and winter, was found in reared bears. Possible factors participating in
      the seasonal variation were discussed with special references to hibernation.

PMID- 8759284
TI  - Kangaroo rat bone compared to white rat bone after short-term disuse and
      exercise.
AB  - Kangaroo rats (Dipodomys ordii) were used to study the effects of confinement on
      mechanical properties of bone with a long range objective of proposing an
      alternative to the white rat model for the study of disuse osteoporosis. Kangaroo
      rats exhibit bipedal locomotion, which subjects their limbs to substantial
      accelerative forces in addition to the normal stress of weight bearing. We
      subjected groups of kangaroo rats and white rats (Rattus norvegicus) to one of
      two confinement treatments or to an exercise regime; animals were exercised at a
      rate calculated to replicate their (respective) daily exercise patterns. White
      laboratory rats were used as the comparison because they are currently the
      accepted model used in the study of disuse osteoporosis. After 6 weeks of
      treatment, rats were killed and the long bones of their hind limbs were tested
      mechanically and examined for histomorphometric changes. We found that kangaroo
      rats held in confinement had less ash content in their hind limbs than exercised
      kangaroo rats. In general, treated kangaroo rats showed morphometric and
      mechanical bone deterioration compared to controls and exercised kangaroo rats
      appeared to have slightly "stronger" bones than confined animals. White rats
      exhibited no significant differences between treatments. These preliminary
      results suggest that kangaroo rats may be an effective model in the study of
      disuse osteoporosis.

PMID- 8759286
TI  - Bibliography of Comparative Biochemistry and Physiology A generated from the
      Current Awareness in Biological Sciences database.

PMID- 8759285
TI  - Effects of concanavalin A and phorbol myristate acetate on glutamine metabolism
      and proliferation of porcine intestinal intraepithelial lymphocytes.
AB  - This study was designed to determine the effects of concanavalin A (ConA) (a T
      cell mitogen) and phorbol myristate acetate (PMA) (an activator of protein kinase
      C) plus ionomycin (Iono) on glutamine metabolism and proliferation of porcine
      intestinal intraepithelial lymphocytes (IEL). IEL were prepared from jejunum of
      29-day-old pigs weaned at 21 days of age. Cells were cultured at 37 degrees C for
      48 hr in RPMI-1640 medium containing 10 mM D-glucose, 0 to 4 mM L-glutamine, 0 to
      5 micrograms/ml ConA, or 20 ng/ml PMA + 375 ng/ml Iono. The medium was also
      supplemented with 0 or 0.1 mM adenosine, guanosine, inosine, uridine or cytosine
      to study the effect of nucleosides or bases on IEL proliferation. IEL
      proliferation was assessed by pulsing with 3H-thymidine for 18 hr. Glutamine
      metabolism was studied in incubated IEL in the presence of Krebs-Henseleit
      bicarbonate buffer containing 5 mM D-glucose and 1 mM L-[U-14C]glutamine.
      PMA+Iono markedly stimulated 3H-thymidine incorporation and glutamine metabolism
      to ammonia, glutamate, aspartate and CO2. When stimulated by PMA+Iono, rates of
      3H-thymidine incorporation and glutamine metabolism were much lower in IEL than
      in mesenteric lymph node lymphocytes. Glutamine was required for IEL
      proliferation, and it could not be replaced by adenosine, guanosine, inosine,
      uridine or cytosine, suggesting that porcine IEL cannot interconvert purine and
      pyrimidine nucleotides. Porcine IEL poorly or not at all responded to ConA
      stimulation, in contrast to lymph node lymphocytes, in terms of both
      [3H]thymidine uptake and glutamine metabolism.

PMID- 8759287
TI  - Isolation of a peptide structurally related to mammalian corticostatins from the
      lamprey Petromyzon marinus.
AB  - Peptides in an extract of skin from the agnathan Petromyzon marinus (sea lamprey)
      were purified by reversed-phase high-performance liquid chromatography and
      characterized by Edman degradation. The primary structure of a cysteine- and
      arginine-rich peptide (termed lamprey corticostatin-related peptide [LCRP]) was
      established as Cys-Pro-Cys-Gly-Arg-Arg-Arg-Cys-Cys-Val-Arg-Gly-Leu-Asn-Val-Tyr
      Cys-Cys- Phe. Mass spectrometry indicated that all cysteine residues are
      intramolecularly linked. This amino acid sequence shows structural similarity to
      rat corticostatin R4 and rabbit corticostatin R1. In particular, LCRP contains
      the polyarginine sequence at the N-terminus of the peptide that is believed to
      mediate both the inhibition of ACTH stimulated steroidogenesis and the
      antimicrobial (defensin-like) actions of the corricostatins.

PMID- 8759288
TI  - Accumulation of uric acid in plasma after repeated bouts of exercise in the
      horse.
AB  - Plasma concentration of uric acid, total peroxyl radical-trapping antioxidative
      parameter (TRAP), blood lactate concentration and plasma activity of xanthine
      oxidase (XO) were measured in six Standardbreed trotters after six bouts of
      exercise with increasing intensity on two separate days three days apart. Blood
      samples were taken immediately, 5, 10, 15, 30 and 60 min after each heat and 2,
      4, and 6 hr after the last heat. Exercise caused an increase in TRAP and in the
      concentrations of lactate and uric acid. Plasma uric acid concentration increased
      exponentially with respect to time after the last heat performed maximal speed,
      indicating a rapid increase in the rate of purine degradation. Plasma XO activity
      increased during exercise, but the intensity of exercise had only a minor effect
      on the level of XO activity. In conclusion, these data suggest that a threshold
      for the plasma accumulation of uric acid in terms of the intensity of exercise
      may exist and that XO may play a role in the formation of uric acid in horse
      plasma. Intense exercise causes an increase in the plasma antioxidant capacity
      that in the horse is mainly caused by the increase in the plasma uric acid
      concentration.

PMID- 8759289
TI  - Modification of DNA topoisomerase I enzymatic activity with phosphotyrosyl
      protein phosphatase and alkaline phosphatase from the hepatopancreas of the
      shrimp Penaeus japonicus (Crustacea:Decapoda).
AB  - DNA topoisomerase I was partially purified from the hepatopancreas of the shrimp
      Penaeus japonicus. The specific activity of the final preparation was 7,000,000
      units/mg of protein with SV40 viral DNA as substrate. SDD-polyacrylamide gel
      electrophoresis of the final preparation yielded two major bands of proteins with
      M(r) 70,000 and M(r) 67,000, as well as less intense bands of proteins with M,
      64,000 and M(r) 56,000. Incubation of the partially purified enzyme fraction with
      rabbit antiserum against human DNA topoisomerase I, allowed all these proteins
      except that of M(r) 56,000, to be positively reacted. Treatment of the partially
      purified DNA topoisomerase I with tyrosine kinase p43v-abl resulted in
      phosphorylation of only the two major subunits. Phosphorylation by tyrosine
      kinase p43v-abl or dephosphorylation by phosphotyrosyl protein phosphatase
      resulted in a decrease of the enzymatic activity. The treatment with shrimp
      alkaline phosphatase abolished the enzymatic activity of the purified DNA
      topoisomerase I in a dose-dependent manner. Thus, the DNA topoisomerase I was
      apparently isolated from the hepatopancreas of the shrimp P. japonicus in a
      phosphorylated form, and this phosphorylation was essential for expression of
      enzymatic activity in vitro. The activity of DNA topoisomerase I is inhibited by
      ZnCl2, CuCl2 and Pb(NH3)3 at millimolar concentrations, but less inhibition was
      observed with CaCl2.

PMID- 8759290
TI  - Role of delivery on serum iron-related parameters in Macaca fascicularis females.
AB  - Few data exist on the iron status and metabolism in macaques, which are
      considered optimal models for the study of reproductive biology and anemia. The
      delivery influence on the hematological parameters of iron metabolism was
      investigated in adult Macaca fascicularis females during late pregnancy and at 6
      weeks postpartum follow-up. No significant differences were detected for each
      parameter by one-way analysis of variance. A decrease of all parameters was
      observed at delivery. During the following weeks, however, the hematological
      values progressively came back to normal. In conclusion, notwithstanding the
      increased need of iron faced during pregnancy, a balanced diet, including iron,
      does not allow the development of either iron deficiency or sideropenic anemia.

PMID- 8759291
TI  - The amino acid sequences, structure comparisons and inhibition kinetics of sheep
      cathepsin L and sheep stefin B.
AB  - Cathepsin L and stefin B were isolated from sheep liver, the cathepsin L being
      isolated by a low pH homogenisation method, which increases the proportion of the
      two-chain form of the enzyme, thus facilitating sequencing. The amino acid
      sequences of the isolated cathepsin L and stefin B were determined. The two-chain
      form of cathepsin L contains 217 amino acid residues and has an M(r) of 23,627.
      The sequence was obtained by sequencing the native active enzyme, the light and
      heavy chains and the peptides generated by cyanogen bromide cleavage. These
      peptides were aligned with peptides obtained by hydrolysis with endoproteinase
      Lys-C, glycyl endopeptidase and endoproteinase Glu-C. Sheep liver cathepsin L
      exhibits a high degree of sequence identity to human cathepsin L. Sheep stefin B
      consists of 98 amino acid residues and its calculated M(r) is 11,150. The
      inhibitor has its NH2-terminal amino acid residue blocked. Its amino acid
      sequence was determined by sequencing the peptides obtained by cleavage with
      cyanogen bromide and peptides obtained by hydrolysis with endoproteinase Glu-C
      and endoproteinase Lys-C. Sheep stefin B shows a high degree of sequence identity
      with bovine and human stefin B. The kinetics of the interaction between sheep
      cathepsin L and stefin B were determined, with the interaction of stefin B with
      papain used as a benchmark to compare with other published results. Despite the
      considerable homology between bovine and sheep stefin B, the kinetics of their
      interaction with papain and cathepsin L differed markedly, possibly due to the
      differences in the so-called "trunk" region of the cystatin molecule.

PMID- 8759292
TI  - Evidence for the presence of two (Ca(2+)-Mg2+) ATPases with different
      sensitivities to thapsigargin and cyclopiazonic acid in the human flatworm
      Schistosoma mansoni.
AB  - The subcellular localization of the (Ca(2+)-Mg2+)ATPase activities present in
      heterogeneous (P1), nuclear (P2), mitochondrial (P3) and microsomal (P4)
      fractions obtained by differential centrifugation of Schistosoma mansoni
      homogenate was investigated. In the microsomal fraction (P4), the (Ca(2+)
      Mg2+)ATPase activity was completely blocked by 3 microM thapsigargin, whereas in
      the more heterogeneous fraction (P1), about 20-30% of this activity was resistant
      to the drug. The same pattern of inhibition was observed using 20 microM
      cyclopiazonic acid. The distribution pattern of (Ca(2+)-Mg2+)ATPase activity
      among the four subcellular fractions (P1 > P4 > > P3 > P2) was completely
      different from that of [3H]-ouabain binding sites (P1 > or = P4 = P2 > or = P3).
      These results indicate that the (Ca(2+)-Mg2+)ATPase in S. mansoni is
      predominantly of the SERCA type (localized in the endoplasmic reticulum).
      However, there is another enzyme, present in lower proportion that could have a
      plasma membrane origin (PMCA type), because it is resistant to thapsigargin and
      cyclopiazonic acid and its inhibition by tamoxifen is antagonized by calmodulin.

PMID- 8759293
TI  - Distribution of phosphoglycerate mutase isozymes in rat, rabbit and human
      tissues.
AB  - The distribution of phosphoglycerate mutase isozymes (types MM, MB and BB) in
      rat, rabbit and human tissues has been studied by electrophoresis on cellulose
      acetate and by highly-resolutive ion exchange chromatography. In the three
      species, muscle is the tissue with higher phosphoglycerate mutase activity. Heart
      is the only tissue with the three phosphoglycerate mutase isozymes in substantial
      amounts. Skeletal muscle contains mostly type MM isozyme and the other tissues
      possess almost exclusively type BB isozyme. Even in the presence of inhibitors,
      adenylate kinase can interfere with the staining reactions when large samples are
      analyzed and a long period of incubation is required.

PMID- 8759294
TI  - Synthesis of vitellogenin polypeptides and deposit of yolk proteins in Anolis
      pulchellus.
AB  - The recognition of liver and serum polypeptides in Anolis pulchellus by a
      polyclonal antibody against S1-lipovitellin confirmed their identity as
      vitellogenins (Vtg) and demonstrated their structural relationship to yolk
      lipoproteins. In vivo labeling demonstrated active synthesis of Vtg by
      vitellogenic females since intracellular incorporation of [3H]-leucine was
      detected at short periods of label in all five Anolis Vtg forms. Time course
      analysis of 3H-Vtg levels indicated a 1 hr lag phase between synthesis and
      secretion. On the other hand, 32P-Vtg appears to be rapidly secreted from the
      liver into the blood since label was detected simultaneously in both
      compartments. After 2 hr intracellular 32P-Vtg levels reached a plateau.
      Decreasing 32P-Vtg levels in the blood were observed several hours after
      injection. In growing oocytes 32P was detected in yolk phosphoproteins ranging
      from 37,000 to 75,000 in molecular weight. Based on these results together with
      previous published data we conclude that in tropical anole the yolk
      phosphoproteins appear to be derived from the larger highly phosphorylated Vtg
      forms according to the typical vertebrate Vtg precursor-product relationship.
      However, the main component of yolk lipovitellin is synthesized in the liver as
      an independent lipoprotein (Vtg-116) which is taken up by growing oocytes without
      major proteolytic modifications. This novel mode of lipovitellin biosynthesis and
      deposit in reptiles has not been reported previously.

PMID- 8759295
TI  - Purification and characterization of a 58,000-Da proteinase inhibitor from the
      hemolymph of a solitary ascidian, Halocynthia roretzi.
AB  - A new endogenous proteinase inhibitor from the cell-free hemolymph of a solitary
      ascidian, Halocynthia roretzi, was purified by a combination of ammonium sulfate
      fractionation, hydrophobic interaction chromatography on Ether-Toyopearl and
      affinity chromatography on Heparin-Sepharose. The purity of the inhibitor was
      examined by SDS-PAGE, gel-permeation chromatography, reversed-phase
      chromatography, isoelectric focusing, immunological analysis and amino-terminal
      amino acid sequence analysis. The inhibitor is a single polypeptide chain whose
      molecular weight, isoelectric point and the first 10 amino-terminal amino acid
      sequences are 58 kDa, pI 9.2 and NH2-Thr-Lys-Lys-Asp-Gly-Glu-Glu-Lys-Val-Ala,
      respectively. The purified protein inhibits plasma enzyme(s) of H. roretzi, and
      the rate of inhibition to the plasma enzyme(s) activity was accelerated by
      incubation with dextran sulfate, but the effect was neutralized by further
      incubation with polycation, such as polybrene or protamine sulfate. The
      inhibitory activity was not affected appreciably by pH 7-10 but ceased completely
      below pH 5 or by heating at 50 degrees C for 30 min.

PMID- 8759296
TI  - Isolation and characterization of Muscovy (Cairna moschata) duck insulin.
AB  - Ducks (Anatidae Family, Anseriform order) are divided in two genera: Pekin duck
      (Anasplatyrhynchos genus) and Muscovy duck (Cairina moschata genus) and differ
      for their number of liver insulin receptors (despite rather similar plasma
      insulin levels). The possibility that the presence of different endogenous
      insulins account for the difference in insulin receptor number between the two
      duck species led us to purify, sequence and characterize the binding properties
      of Muscovy duck insulin. The sequence of Muscovy duck insulin (measured mass:
      5729.11) was identical to that described in two other species from the
      Anseriforme order: Pekin duck or goose. The binding affinity of Muscovy duck
      insulin for rat liver insulin receptors (either membrane bound or solubilized
      receptors) was lower than that of porcine insulin (0.3), which most likely
      accounts for the low biological potency of Pekin duck insulin previously
      described. In contrast, liver receptors from chicken and both duck species
      exhibited the same affinity for duck and porcine insulin suggesting the presence
      of specific changes in the structure of binding sites of bird liver insulin
      receptors. The decrease in the number of insulin receptors in Muscovy duck liver
      is not therefore the consequence of a change at the level of the insulin molecule
      itself. As discussed, among bird insulins, the hypoactive "duck type" insulin
      would have appeared after the hyperactive "chicken type" insulin during the
      evolution of Aves.

PMID- 8759297
TI  - Evaluation of solubilizing methods of the egg envelope of the fish, Oryzias
      latipes, and partial determination of amino acid sequence of its subunit protein,
      ZI-3.
AB  - The inner layer of most teleostean egg envelopes, especially those after
      hardening, is almost insoluble in ordinary solvent, and therefore the inner layer
      of only the unhardened egg envelope has been subjected to solubilization with
      some potent solvents. We comparatively evaluated the methods of solubilization of
      the inner layer of egg envelope of medaka, Oryzias latipes, with SDS, urea and
      guanidium chloride (GuHCI). Analysis of the solubilized samples by SDS
      polyacrylamide gel electrophoresis, comparison of their amino acid compositions
      or peptide maps using high-performance liquid chromatography and partial
      determination of their amino acid sequences showed that SDS and GuHCI were
      appropriate for solubilization and characterization of the envelope. Urea
      solubilization resulted in some artificial modifications of lysine and/or
      cysteine residues of envelope proteins. Partial determination of amino acid
      sequence of a subunit, ZI-3, isolated from the SDS-or GuHCI-solubilized envelope
      strongly suggested the identity of the envelope subunit, ZI-3, and its precursor,
      L-SF.

PMID- 8759298
TI  - A glucokinase-like-enzyme in the liver of Atlantic salmon (Salmo salar).
AB  - An enzyme with properties similar to rat liver glucokinase (Hexokinase IV or D)
      is present in salmon liver in addition to low-Km hexokinase(s). The specific
      activity of this enzyme increases about 1.6 fold, comparing activities after
      feeding diets with 25% and 0% digestive energy from starch. The enzyme has a low
      affinity for glucose, S0.5 = 25.2-26.8 mM (95% confidence interval) and a low
      activity with fructose, approximately 8% of the activity with glucose. Its
      molecular mass was estimated to 50.7 +/- 0.6 kDa (SEM. n = 3) by gel filtration,
      and it displays positive cooperativity with respect to glucose. The Hill constant
      = 1.73-1.81 (95% confidence interval). The enzyme is competitively inhibited by N
      acetyl glucosamine, K(i) approximately 0.28 mM.

PMID- 8759299
TI  - Purification and some properties of a carboxylesterase from ovine liver.
AB  - Carboxylesterase ESB3 was extracted from ovine liver and purified to homogeneity
      by ammonium sulphate fractionation, hydrophobic interaction chromatography on
      Phenyl Sepharose, ion exchange chromatography on Mono-Q Sepharose and size
      exclusion chromatography on Superose 6. The enzyme is free of carboxylesterase
      ESB2 activity. The molecular mass of the enzyme is estimated 182 kDa as judged by
      size exclusion chromatography. Isoelectric focusing indicates the presence of six
      isoforms of pI 5.50-5.77 with three main isoforms of pI 5.55-5.65. The enzyme is
      active towards the substrates p-nitrophenyl acetate and the aliphatic substrates
      ethyl acetate, ethyl propionate, ethyl butyrate, and ethyl valerate. Of the ethyl
      esters the affinity is lowest towards acetate and highest towards ethyl butyrate.
      The enzyme is totally inhibited by phenylmethylsulphonyl fluoride (PMSF) and
      mercuric chloride but not affected by eserine or cupric chloride. The pH optimum
      of the enzyme is 7.5 and it is stable at 55 degrees C for 20 min.

PMID- 8759300
TI  - Chylomicron triacylglycerol fatty acids in suckling northern elephant seals
      (Mirounga angustirostris) resemble the composition and the distribution of fatty
      acids in milk fat.
AB  - Following birth, the northern elephant seal (Mirounga angustirostris) pups
      rapidly gain weight by ingesting milk with a high fat content, as much as 50%. To
      better understand the metabolism of the pups during the suckling period, the
      positional distributions of triacylglycerol fatty acids in both the milk and
      chylomicra were determined. Extracts of enzymatically digested lipids were
      separated by thin layer chromatography and the constituent fatty acids were
      separated and quantified by gas liquid chromatography. Over 84% of the fatty
      acids were either monoenoic or saturated, with the ratio of monoenoic to
      saturated fatty acids ranging between 2.9-4.0. Positional distributional analyses
      revealed that the very long chain monoenoics (20:1 and 22:1) were located
      primarily at the sn-1,3 positions of milk triacylglycerols. In the interval
      between the onset of lactation to the time of weaning, the content of these very
      long chain monoenoic fatty acids at the sn-1,3 positions increased from 13-37%.
      At the sn-2 position, the percentage of 18:1 was 3-5-fold higher than 16:1.
      Analyses indicated that the triacylglycerols in both milk and suckling pup
      chylomicra were similar. This particularly was true for the distributions at the
      sn-2 position, indicating that milk fats are being absorbed primarily via the 2
      monoacylglycerol pathway.

PMID- 8759301
TI  - Pressure effects on metabolism in tissues from mice (Mus muscalis) and freshwater
      mussel (Elliptio complanata).
AB  - Metabolic rates of tissue sections from freshwater mussel gills and mouse brain
      and lung tissue were measured by calorimetry in ampules pressurized with gas
      mixtures. Increasing partial pressure of oxygen or total pressure with constant
      partial pressure of O2 does not affect the respiratory quotient but increases
      rates of tissue metabolism. Changes in metabolic activity occur over pressure and
      Po2 ranges commonly encountered by humans engaged in SCUBA diving.

PMID- 8759302
TI  - Diurnal variability of cysteine and glutathione content in the pancreas and liver
      of the mouse.
AB  - The sensitivity of organs such as the liver to injury by certain drugs is
      modulated by the endogenous capacity to synthesize glutathione during periods of
      increased demand. Recent experimental evidence suggests that glutathione
      availability could also play an important role in preventing pancreatic injury as
      well. To better understand the role of cysteine availability in regulating
      glutathione homeostasis in the pancreas and liver under normal conditions, the
      diurnal variation in cysteine in mouse pancreas and liver was measured and
      compared with corresponding measurements of organ glutathione content. Pancreatic
      cysteine varied significantly over a 24-hr period, dropping to 21 nmol/g at 2
      P.M. and rising to 68 nmol/g at 10 P.M. Fasting prevented this diurnal variation
      in pancreatic cysteine. Pancreatic glutathione was at its lowest at 10 P.M. and
      rose sharply to a peak at 2 A.M. Fasting had no effect on this diurnal pattern.
      In contrast to the pancreas, fasting did not prevent the diurnal change in liver
      cysteine, whereas it caused substantial depletion of liver glutathione. Together,
      these findings suggest that under normal conditions, pancreatic and liver
      glutathione content are not determined solely by tissue cysteine availability.
      Moreover, basal glutathione content is under differing homeostatic mechanisms in
      the pancreas and the liver.

PMID- 8759303
TI  - Age-related changes in branched-chain fatty acid concentration of the skin
      surface lipid from hairless mouse.
AB  - Age-related changes in branched chain fatty acid (BCFA) concentration were
      studied with the skin surface lipid from hairless mice. A large proportion of
      BCFA was present in the cholesterol ester (CE) and wax diester (WDE) fraction of
      the skin surface lipid from hairless mice. The concentration of iso-series BCFA
      was highest at infancy and decreased with advancing age in both CE and WDE
      fraction. The concentration of anteiso-series BCFA appeared to be constant
      throughout the experiment.

PMID- 8759304
TI  - Comparative properties of arginases.
AB  - Arginase is a primordial enzyme, widely distributed in the biosphere and
      represented in all primary kingdoms. It plays a critical role in the hepatic
      metabolism of most higher organisms as a cardinal component of the urea cycle.
      Additionally, it occurs in numerous organisms and tissues where there is no
      functioning urea cycle. Many extrahepatic tissues have been shown to contain a
      second form of arginase, closely related to the hepatic enzyme but encoded by a
      distinct gene or genes and involved in a host of physiological roles. A variety
      of functions has been proposed for the "extrahepatic" arginases over the last
      three decades. In recent years, interest in arginase has been stimulated by a
      demonstrated involvement in the metabolism of the ubiquitous and multifaceted
      molecule nitric oxide. Molecular biology has begun to furnish new clues to the
      disparate functions of arginases in different environments and organisms.
      Comparative studies of arginase sequences are also beginning to elucidate the
      comparative evolution of arginases, their molecular structures and the nature of
      their catalytic mechanism. Further studies have sought to clarify the involvement
      of arginase in human disease. This review presents an outline of the current
      state of arginase research by giving a comparative overview of arginases and
      their associated properties.

PMID- 8759305
TI  - Bibliography for Comparative Biochemistry and Physiology B generated from the
      Current Awareness in Biological Sciences database.

PMID- 8759306
TI  - Micelle-like conformation of humic substances as revealed by size exclusion
      chromatography.
AB  - To gain further insight into the macromolecular behaviour of humic substances we
      treated a humic material with simple organic compounds and followed the change in
      molecular size distribution. Monocarboxylic, dicarboxylic, and tricarboxylic
      acids shifted the humic absorbance from high to low molecular sizes in size
      exclusion chromatograms. Mineral acids, phenol, alcohols, were not able to
      produce the same shift and gave total absorbance at the column void volume as in
      the case of humic substances alone. Our results are evidence of the micellar
      behaviour of humic substances in solution and of the importance of hydrophobic
      bondings in holding humic molecules together. The organic acids enter in the
      interior of the humic micelle and alter its stereochemical hydrophobic
      arrangement. In alkaline conditions, the developed negative charges disrupt the
      apparent high molecular size configuration and disperse the humic material into
      small-size micelles. This macromolecular property, that we report for the first
      time, may be of great importance in understanding the biological activity and the
      overall environmental behaviour of humic substances.

PMID- 8759307
TI  - Determination of pentachlorophenol in commercially prepared lyophilized human
      urine control samples.
AB  - Commercially available reference materials consisting of lyophilized human urine
      are routinely utilized by clinical chemists to monitor laboratory performance for
      a variety of analyses. In this study commercially prepared lyophilized human
      urine control samples were reconstituted and analyzed for pentachlorophenol.
      Based on replicate analyses of two different reference materials, the levels of
      PCP in each were found to be representative of the levels typically present in
      urine samples collected from the general population of the province of
      Saskatchewan.

PMID- 8759308
TI  - Biodegradability simulation studies in semicontinuous activated sludge reactors
      with low (microgram/L range) and standard (ppm range) chemical concentrations.
AB  - The official OECD/EEC activated-sludge biodegradability simulation test has been
      criticised for providing a poor simulation of the biodegradability behaviour of
      industrial chemicals in municipal sewage treatment plants due to the high dosed
      concentration of test substance of approx. 20-40 mg/L necessitated by measuring
      compound removal by DOC-analysis. Realistic concentrations of industrial
      chemicals are more commonly in the microgram/L range. With increasing
      concentration both the kinetic regime of degradation and the adaptation behaviour
      can be expected to change. Results from a comparative study in semicontinuous
      reactors with high (20 mg DOC/L) and low (10 micrograms test substance/L) inlet
      concentrations of aniline, 4-chloroaniline, and pentachlorophenol, conducted by
      means of 14C-tracer technique, revealed large differences in biodegradation
      behaviour between the two concentration levels and led to the following tentative
      general conclusions: 1) the percentage of test compound removed by unadapted
      sludge tends to be higher with test compound dosed at trace concentrations than
      at standard (high) concentrations (20 mg/DOC/L); 2) by contrast, in successfully
      adapted systems, the removal percentage (and the "extent of adaptation") may be
      largest with high concentrations; 3) the use of real sewage instead of peptone
      synthetic sewage better safeguards against sludge deterioration, in particular at
      low sludge retention times, and tends to increase the adaptation potential of the
      sludge; 4) the use of synthetic sewage in combination with regular reinoculation
      of the reactor (in this study by replacing 10% of the sludge with freshly
      collected sludge once a week) may be a feasible alternative to using real sewage.

PMID- 8759309
TI  - Metabolism of organochlorine pesticides: the role of human cytochrome P450 3A4.
AB  - Organochlorine compounds are widely used as pesticides and are substantial
      environmental pollutants and carcinogens due to their extensive environmental
      release. In the present study biotransformation of these pesticides was observed
      in the microsomal fractions and whole cells of Saccharomyces cerevisiae
      expressing human cytochrome P450 3A4. In both in vitro and in vivo studies,
      hexachlorobenzene and pentachlorobenzene were metabolised into pentachlorophenol
      which was further transformed into tetrachlorohydroquinone. Metabolites were
      identified by thin layer chromatography and 13C-NMR spectroscopy. The formation
      of products was observed only in the presence NADPH in microsomal fractions and
      no activity was observed in control microsomal fractions, or in whole cells.

PMID- 8759310
TI  - Survey of consumption fish from Swedish waters for chlorinated pesticides and
      polychlorinated biphenyls.
AB  - In this survey eighty-seven samples of consumption fish comprising mainly of
      salmon, pike, eel, herring, whitefish, sea-trout, perch, pike-perch, mackerel,
      cod, flounder, plaice and sole collected between 1992-1993 have been analysed for
      the levels of chlorinated pesticides and polychlorinated biphenyls (PCBs).
      Considering the diversity in the sizes and assortment, locations, and time of
      catch, the samples are deemed to represent the normal fish variety available to
      the local people at various seasons of the year. Virtually all the samples
      contained CB-153 levels below the new established maximum limit of 0.1 mg/kg
      fresh weight. Results are compared with those obtained between 1985 and 1993.
      Neither the total PCB (on fat weight basis) nor CB 153 as a marker showed any
      clear trend for most of the fish species analysed, particularly for the short
      period 1991-1993. The pesticides, on the other hand, showed a rather good
      downward trend up till 1991; some of them seem to have virtually attained a
      steady state after 1991.

PMID- 8759311
TI  - An energy budget model for the biodegradation and cometabolism of organic
      substances.
AB  - Expression of bacterial cellular processes (maintenance, heat loss, growth,
      cometabolism and substrate degradation) into energy units yielded surprisingly
      realistic figures on the bacterial energy balance in spite of the severe
      approximations and assumptions that had to be made. For studies without
      cometabolism, 47-83% of the calculated amount of available energy was consumed by
      growth; for maintenance + heat loss this percentage was 20-35%. When involved,
      cometabolism consumed 7-13% of the total energy budget. Overall, 67-118% of the
      calculated amount of energy generated was spent on these energy-consuming
      processes. This shows that the model is internally consistent. Relationships
      between growth and cometabolism may offer predictions of persistence of
      cometabolizable chemicals under different conditions. The energy budget model as
      presented provides a starting point for the development of such relationships. In
      addition, the method is used to explain threshold concentrations, below which
      normally degradable compounds are not degraded.

PMID- 8759312
TI  - Estimation of kinetic rate constants for biodegradation of chemicals in activated
      sludge wastewater treatment plants using short term batch experiments and
      microgram/L range spiked concentrations.
AB  - Biodegradation rate constants that are believed to be predictive for activated
      sludge sewage treatment plants have been determined at microgram/L concentration
      levels using short term (hours) laboratory scale batch experiments with activated
      sludge. Rate constants were estimated for four model chemicals with widely
      different biodegradability characteristics, and experiments were conducted with
      sludges of various origin and treatment. Test substances were applied at
      concentrations ranging from a few microgram/L for deriving first order rate
      constants and up to several mg/L for full investigation of the kinetics. Model
      substances were acetate, aniline, 4-chloroaniline and pentachlorophenol and their
      biodegradation was assessed by means of 14C tracer technique. Some experiments
      included test concentrations equal to those prescribed in standard
      biodegradability tests (20 mg DOC/L). Sludge types investigated included adapted
      and non-adapted sludge from laboratory scale semicontinuous reactors as well as
      sludges collected from a pilot scale sewage treatment plant loaded with
      predominantly domestic sewage. At low chemical concentrations ( < approx. 100
      micrograms/L) first order degradation rate constants were reasonably constant and
      varied only little with the applied concentration. With aniline, however,
      elimination rates increased at concentrations below about 20 micrograms/L,
      probably because transient sorption became significant. At higher concentrations
      absolute (linear) degradation rates could be described by saturation kinetics,
      and for aniline a half saturation constant, K(S), was estimated at 3 mg/L. "Best
      estimates" of average first order rate constants in the low concentration regime
      measured with 3 g SS/L and at 22 degrees C were: acetate, 8 h-1; aniline, 0.8 h
      1, 4-chloroaniline, 0.15 h-1, and pentachlorophenol, 0.01 h-1 (non adapted
      sludge) or 0.02 h-1 (adapted sludge). These figures seem to agree well with
      standard or default biodegradation rate constants for sewage treatment plants
      suggested in a European Union technical guidance document for chemical risk
      assessment, which is currently under preparation.

PMID- 8759313
TI  - Determination of bioconcentration potential of tetrachloroethylene in marine
      algae by 13C.
AB  - The use of stable isotope of organic-carbon, organic-13C, as a tracer for the
      determination of the concentration of tetrachloroethylene (PCE), CA, in
      Heterosigma akashiwo and Skeletonema costatum was examined. CA determined by the
      13C and GC methods showed good agreement with each other. This suggests that it
      is reasonable and reliable to determine the bioconcentration potential of PCE in
      marine algae. Fitting values of bioconcentration potential parameters, including
      uptake rate constant k1, elimination rate constant k2 and bioconcentration factor
      on the basis of dry weight BCFD, were done not only to the time course for PCE
      uptake by the algae with the bioconcentration model, but also to experimental
      data for "percent inhibition(%) approximately exposure concentration of PCE
      approximately time" with the combined bioconcentration and probability model. The
      values obtained from the bioconcentration model were consistent with those from
      the combined bioconcentration and probability model. With the parameters (such as
      k1, k2, growth rate constant kG, critical concentration of HOCs in the organism
      resulting in growth inhibition CA* and spread factor S) the variability in
      toxicity (such as EC10, EC50, EC70) can be estimated from the combined
      bioconcentration and probability model, which fits well with the experimental
      observations.

PMID- 8759314
TI  - A characteristic bent conformation of RNA pseudoknots promotes -1 frameshifting
      during translation of retroviral RNA.
AB  - The structures of four different RNA pseudoknots that provide one of the signals
      required for ribosomal frameshifting in mouse mammary tumor virus have been
      determined by NMR. The RNA pseudoknots have similar sequences and assume similar
      secondary structures, but show significantly different frameshifting
      efficiencies. The three-dimensional structures of one frameshifting and one non
      frameshifting RNA pseudoknot had been determined previously by our group. Here we
      determine the structures of two new RNA pseudoknots, and relate the structures of
      all four pseudoknots to their frameshifting abilities. The two efficient
      frameshifting pseudoknots adopt characteristic bent conformations with stem 1
      bending towards the major groove of stem 2. In contrast, the two poor
      frameshifting pseudoknots have structures very different from each other and from
      the efficient frameshifters. One has linear, coaxially stacked stems, the other
      has stems twisted and bent, but in the opposite direction to the efficient
      frameshifters. Changes in loop size that favor bending (shorter loops) increase
      frameshifting efficiency; longer loops that allow linear arrangement of the stems
      decrease frameshifting. Frameshifting pseudoknots in feline immunodeficiency
      virus and simian retrovirus have different loop sequences, but the sequences at
      their stem junctions imply the same bent conformation as in the mouse mammary
      tumor viral RNA. The requirement for a precise pseudoknot conformation for
      efficient frameshifting strongly implies that a specific interaction occurs
      between the viral RNA pseudoknot and the host protein-synthesizing machinery.

PMID- 8759315
TI  - Identification of an UP element within the IHF binding site at the PL1-PL2 tandem
      promoter of bacteriophage lambda.
AB  - An UP element defines a supplementary promoter element located upstream of the 
      35 region that stimulates transcription by interacting with the C-terminal domain
      of the RNA polymerase alpha subunit (alpha CTD). The alpha CTD also responds to
      various transcription activators, including the integration host factor protein,
      IHF, in the stimulation of the bacteriophage lambda PL promoter. PL consists of
      the tandem PL1-PL2 promoters where PL1 is stimulated and PL2 is repressed by IHF.
      We identified a functional UP element that binds the alpha subunit of RNA
      polymerase and is located in the region from -36 to -60 relative to the PL2 start
      site. PL2 expression requires the presence of the UP element and requires an
      intact alpha CTD. The UP element is nested within the DNA region protected by IHF
      against DNase I digestion. We used mutational analysis to identify the IHF
      recognition sequence which was found to be located downstream of the UP element,
      overlapping the -35 region of PL2. The possible function of the complex structure
      of the PL promoter is discussed.

PMID- 8759316
TI  - Isolation of 88F actin mutants of Drosophila melanogaster and possible
      alterations in the mutant actin structures.
AB  - The 88F actin (act88F) gene of Drosophila, melanogaster encodes an actin isoform
      that is expressed exclusively in the indirect flight muscle. In order to isolate
      a large number of act88F mutants, an efficient screening method was used to
      obtain dominant flightless mutants. Genetic analyses revealed that 25 mutations
      were located near or at the act88F locus. From each mutant strain, the DNA
      fragments including the coding region of the act88F gene were asymmetrically
      amplified by the polymerase chain reaction method, and the amplified fragments
      were directly sequenced. Eighteen of them were found to have point mutations
      within their coding regions. Of these, 13 were novel alleles of this gene. We
      have characterised these mutations in detail. First, their flight abilities were
      tested after introducing two normal alleles of this gene. Second, two-dimensional
      gel electrophoresis was used to examine actin isoforms and whole thorax proteins.
      Third, morphological anomalies of indirect flight muscle fibres and myofibrils
      were examined with an optical microscope. On the basis of these phenotypes and
      the known atomic structure of actin, possible alterations in the structure of
      actin brought about by these mutations are discussed.

PMID- 8759317
TI  - Homologous recombination between the tuf genes of Salmonella typhimurium.
AB  - The genes coding for the translation factor EF-Tu, tufA and tufB are separated by
      over 700 kb on the circular chromosome of Salmonella typhimurium. The coding
      regions of these genes have 99% identity at the nucleotide level in spite of the
      presumed ancient origin of the gene duplication. Sequence comparisons between S.
      typhimurium and Escherichia coli suggest that within each species the two tuf
      genes are evolving in concert. Here we show that each of the S. typhimurium tuf
      genes can transfer genetic information to the other. In our genetic system the
      transfers are seen as non-reciprocal, i.e. as gene conversion events. However,
      the mechanism of recombination could be reciprocal, with sister chromosome
      segregation and selection leading to the isolation of a particular class of
      recombinant. The amount of sequence information transferred in individual
      recombination events varies, but can be close to the entire length of the gene.
      The recombination is RecABCD-dependent, and is opposed by MutSHLU mismatch
      repair. In the wild-type, this type of recombination occurs at a rate that is two
      or three orders of magnitude greater than the nucleotide substitution rate. The
      rate of recombination differs by six orders of magnitude between a recA and a
      mutS strain. Mismatch repair reduces the rate of this recombination 1000-fold.
      The rate of recombination also differs by one order of magnitude depending on
      which tuf gene is donating the sequence selected for. We discuss three classes of
      model that could, in principle, account for the sequence transfers: (1) tuf mRNA
      mediated recombination; (2) non-allelic reciprocal recombination involving sister
      chromosomes; (3) non-allelic gene conversion involving sister chromosomes,
      initiated by a double-strand break close to one tuf gene. Although the mechanism
      remains to be determined, the effect on the bacterial cells is tuf gene sequence
      homogenisation. This recombination phenomenon can account for the concerted
      evolution of the tuf genes.

PMID- 8759318
TI  - DNA-stacking interactions determine the sequence specificity of the
      deoxyribonuclease activity of 1,10-phenanthroline-copper ion.
AB  - Bis(1,10-phenanthroline)-copper(I) ion (OP2Cu+) binds reversibly to B-DNA and
      makes single-stranded cuts by oxidative attack on the deoxyribose moiety. The
      deoxyribonuclease activity is sequence-dependent yet not nucleotide-specific at
      the cutting site. OP2Cu+ sequence specificity was analysed in terms of local
      variations of DNA stability. Kinetic constants of strand cleavage were measured
      at sequence positions on the two strands and converted into activation free
      energies of the cleavage reaction. DNA unwinding free energies were calculated
      from the base sequence using B-DNA stacking parameters for calculations. The two
      free-energy variations were statistically compared for a series of DNA
      restriction fragments bearing the binding sites of regulatory proteins and
      representing a total of 345 DNA base positions. This study shows that the mean
      activation free energy of strand cleavage at a pair of opposing sugars across the
      DNA minor groove varies like the unwinding free energy of the DNA sequence
      delimited by opposing sugars (3 to 4 bp). A statistical equality between the two
      free-energy variations is demonstrated when considering the sum of the two
      cleavage events at the opposing sugars. Systematic deviations between the two
      free-energy distributions were observed at specific sequences, including
      polypurine-polypyrimidine tracts (AnTm/AmTn, CnTmCp/GpAmGn), alternating purine
      pyrimidine tracts ((TA)n/(TA)n, (TG)n/(CA)n) and at certain G+C-rich triplets
      (GGC, GCC and CGC). The physical significance of these observations is discussed
      and a model of OP2Cu+ binding and cleavage specificity based on the free-energy
      equality is proposed.

PMID- 8759319
TI  - X-ray crystallographic structure of recombinant eosinophil-derived neurotoxin at
      1.83 A resolution.
AB  - The X-ray crystallographic structure of recombinant eosinophil-derived neurotoxin
      (rEDN) has been determined by molecular replacement methods and refined at 1.83 A
      resolution to a conventional R-factor ( = sigma magnitute of (magnitute of
      F(zero)-magnitude of Fc)/ sigma magnitude of F(zero) of 0.152 with excellent
      stereochemistry. The molecular model of rEDN contains all 1081 non-hydrogen
      protein atoms, two non-covalently bound sulfate anions and 121 ordered solvent
      molecules. The polypeptide fold of rEDN is related to those observed in the
      homologous structures of RNase A, Onconase and angiogenin. rEDN is one of the
      largest members of the pyrimidine-specific ribonuclease superfamily of
      vertebrates and has small insertions in four of its seven loop structures and a
      large insertion from Asp115 to Tyr123. The non-covalently bound SO4(A) and SO4(B)
      anions occupy phosphate-binding subsites of rEDN. The active site SO4(A) anion
      makes contacts in rEDN that are similar to those in RNase A and involve the side
      chain atoms of Gln14, His15 and His129, and the NH group of Leu130. The SO4(B)
      anion makes contacts with the side-chain atoms of Arg36 and Asn39 and the main
      chain atoms of Asn39 and Gln40. The equivalent residues of RNase A cannot make
      contacts similar to those observed in rEDN. The SO4(B) binding site of rEDN
      likely corresponds to the P-1 subsite and may be representative of how other
      homologous RNases bind the P-1 phosphate.

PMID- 8759320
TI  - The refined crystal structure of toxic shock syndrome toxin-1 at 2.07 A
      resolution.
AB  - The pyrogenic toxin toxic shock syndrome toxin-1 from Staphylococcus aureus is a
      causative agent of the toxic shock syndrome disease. It belongs to a family of
      proteins known as superantigens that cross-link major histocompatibility class II
      molecules and T-cell receptors leading to the activation of a substantial number
      of T cells. The crystal structure of this protein has been refined to 2.07 A with
      an Rcryst value of 20.4% for 51,240 reflections. The final model contains three
      molecules in the asymmetric unit with good stereochemistry and a root-mean-square
      deviation of 0.009 A and 1.63 from ideality for bond lengths and bond angles,
      respectively. The overall fold is considerably similar to that of other known
      microbial superantigens (staphylococcal enterotoxins). However, a detailed
      structural analysis shows that toxic shock syndrome toxin-1 lacks several
      structural features that affect its specificity for V beta elements of the T-cell
      receptor and also its recognition by major histocompatibility class II molecules.

PMID- 8759321
TI  - Accretion of structure in staphylococcal nuclease: an 15N NMR relaxation study.
AB  - 15N main-chain dynamics are compared in four forms of staphylococcal nuclease
      with different stabilities to unfolding: (1) SN-T, the ternary complex of the
      protein, Ca2+, and the inhibitor thymidine 3', 5'-bisphosphate; (2) SN, the
      protein in the absence of added ligands; (3) SN-OB, a folded fragment that
      corresponds to an "OB-fold" subdomain; (4) delta 131 delta, a denatured 131
      residue fragment. SN-T exhibits very little internal motion on the nanosecond
      timescale. In SN, a moderate increase in flexibility is observed for the first
      three strands of the five-stranded beta-sheet, and for a loop between strands 4
      and 5. In SN-OB, the loops between strands 3 and 4, and between strands 4 and 5,
      are extremely flexible on the nanosecond timescale. While the beta-sheets of SN
      OB and SN have comparable dynamics on the nanosecond timescale, the beta-sheet in
      SN-OB experiences additional motion on a slower timescale of 330(+/-170)
      microseconds. We attribute the latter to interconversion between a major folded
      (> or = 98%) and a minor unfolded (> or = 2%) conformation. In delta 131 delta,
      the first three strands of beta-sheet experience conformational averaging on the
      millisecond timescale. Most of the remainder of the polypeptide chain is highly
      flexible on the nanosecond timescale. When all four forms of nuclease are
      considered, there is an increase in the proportion of residues with large
      amplitude internal motions (low order parameters) as the stability of the folded
      state is decreased. Residues with low order parameters cluster to distinct
      regions of the chain, and have H alpha chemical shifts and 3JHN-H alpha coupling
      constants that tend towards "random coil" values. Conversely, a trend towards
      uniformly high order parameters suggests a consolidation of structure with
      increasing stability to denaturation.

PMID- 8759322
TI  - The hydration of globular proteins as derived from volume and compressibility
      measurements: cross correlating thermodynamic and structural data.
AB  - We report the first thermodynamic characterization of protein hydration that does
      not depend on model compound data but rather is based exclusively on macroscopic
      (volumetric) and microscopic (X-ray) measurements on protein molecules
      themselves. By combining these macroscopic and microscopic characterizations, we
      describe a quantitative model that allows one for the first time to predict the
      partial specific volumes, v(zero), and the partial specific adiabatic
      compressibilities, ks(zero), of globular proteins from the crystallographic
      coordinates of the constituent atoms, without using data derived from studies on
      low-molecular-mass model compounds. Specifically, we have used acoustic and
      densimetric techniques to determine v(zero) and ks(zero) for 15 globular proteins
      over a temperature range from 18 to 55 degrees C. For the subset of the 12
      proteins with known three-dimensional structures, we calculated the molecular
      volumes as well as the solvent-accessible surface areas of the constituent
      charged, polar and nonpolar atomic groups. By combining these measured and
      calculated properties and applying linear regression analysis, we determined, as
      a function of temperature, the average hydration contributions to v(zero) and
      ks(zero) of 1 A2 of the charged, polar, and nonpolar solvent-accessible protein
      surfaces. We compared these results with those derived from studies on low
      molecular-mass compounds to assess the validity of existing models of protein
      hydration based on small molecule data. This comparison revealed the following
      features: the hydration contributions to v(zero) and ks(zero) of charged protein
      surface groups are similar to those of charged groups in small organic molecules.
      By contrast, the hydration contributions to v(zero) and ks(zero) of polar protein
      surface groups are qualitatively different from those of polar groups in low
      molecular-mass compounds. We suggest that this disparity may reflect the presence
      of networks of water molecules adjacent to polar protein surface areas, with
      these networks involving waters from second and third coordination spheres. For
      nonpolar protein surface groups, we find the ability of low-molecular-mass
      compounds to model successfully protein properties depends on the temperature
      domain being examined. Specifically, at room temperatures and below, the
      hydration contribution to ks(zero) of protein nonpolar surface atomic groups is
      close to that of nonpolar groups in small organic molecules. By contrast, at
      higher temperatures, the hydration contribution to ks(zero) of protein nonpolar
      surface groups becomes more negative than that of nonpolar groups in small
      organic molecules. We suggest that this behaviour may reflect nonpolar groups on
      protein surfaces being hydrated independently at low temperatures, while at
      higher temperatures some of the solvating waters become influenced by neighboring
      polar groups. We discuss the implications of our aggregate results in terms of
      various approaches currently being used to describe the hydration properties of
      globular proteins, particularly focusing on the limitations of existing additive
      models based on small molecule data.

PMID- 8759324
TI  - Determination of melengestrol acetate in supercritical fluid-solid phase extracts
      of bovine fat tissue by HPLC-UV and GC-MS.
AB  - A method is developed for the determination of melengestrol acetate in bovine fat
      tissue at or less than the established tolerance level of 25 ppb. The procedure
      uses a combination of supercritical fluid extraction (SFE) and solid-phase
      extraction (SPE) techniques to produce an extract suitable for analysis with
      either high-performance liquid chromatography with ultraviolet detection or gas
      chromatography-mass spectrometry. Overall recovery of the analyte from bovine fat
      tissue is 99.4% with a coefficient of variation of 4.14%. The SFE-SPE procedure
      uses a total of 12 mL of organic solvent per fat tissue sample versus more than
      1.7 L consumed in current extraction procedures.

PMID- 8759323
TI  - A dataset of protein-protein interfaces generated with a sequence-order
      independent comparison technique.
AB  - While there are a number of structurally non-redundant datasets of protein
      monomers, there is none of protein-protein interfaces. Yet, the availability of
      such a dataset is expected to provide an added insight into a number of
      investigations. First and foremost among these is analyzing the interfaces to
      obtain their prevailing architectures, the forces that account for the protein
      protein associations and their packing considerations. Their comparisons with
      those of the monomers are likely to shed additional light on protein-protein
      recognition on the one hand and on the folding of the polypeptide chain on the
      other. Docking simulations are also expected to benefit from the existence of
      such a dataset. A major stumbling block to the generation of a dataset of
      interfaces has been that the interface is composed of at least two chains.
      Furthermore, in the interfaces, each of the chains might be represented by non
      contiguous pieces. Their order in the interfaces being compared might be
      different as well. This discontinuity stems from the definition of an interface.
      An interface consists of interacting residues between the chains, and those that
      are in their vicinity in the supporting scaffold, within a certain distance
      threshold. This necessarily yields unordered fragments, as well as isolated
      residues. Our novel, efficient, sequence-order-independent structural comparison
      technique is ideally suited to handle the task of the generation of a library of
      structurally non-redundant protein-protein interfaces. As it is computer-vision
      based, it views atoms as collections of points in space, disregarding their chain
      connectivity. In this work, 351 interface-families are created. Comparisons of
      the interfaces, and separately, of the chains which contribute to them, yield
      some interesting cases. In one of the cases, while two interfaces are similar,
      the structure of only one of the two chains is similar between the two complexes.
      The structure of the second chain of the first complex differs from that of the
      second chain of the second complex. Here the structure of the cleft in the first
      chain dictates the specific binding interactions. In another case, while the
      interfaces in the two complexes are similar, both chains composing them differ
      between the complexes. Lastly, the chains composing the complexes are similar,
      but the interfaces are dissimilar, providing a set of data for investigations of
      the favorable orientations of protein-protein associations.

PMID- 8759325
TI  - A modified procedure for caseinophosphopeptide analysis.
AB  - A modified procedure is established for analyzing caseinophosphopeptides. The
      sodium caseinate hydrolysate is first treated by immobilized metal ion affinity
      chromatography to enrich the phosphopeptides. Because of the formation of Fe(3+)
      peptide complexes, ethylenediaminetetraacetic acid is added to the bound fraction
      eluted with the immobilized metal ion affinity chromatography to disintegrate the
      complexes. Thus, the subsequent high-performance liquid chromatographic analysis
      is facilitated. A stepwise gradient elution is also suggested to enhance the
      resolution of caseinophosphopeptides during high-performance liquid
      chromatographic analysis.

PMID- 8759326
TI  - Rapid screening of taxol metabolites in human microsomes by liquid
      chromatography/electrospray ionization-mass spectrometry.
AB  - Liquid chromatography with an electrospray ionization (ESI) interface has been
      applied to study the anticancer drug taxol and its metabolites after incubation
      with human hepatic microsomes. The parent drug and its metabolites were monitored
      in the positive-ionization mode. Since ESI gave only quasi-molecular ions for
      taxol and its analogues, collision-induced dissociation experiments were carried
      out in order to generate fragment ions, by increasing the cone voltage at the ESI
      source. The product-ion mass spectra of taxol and its metabolites contained
      diagnostic fragment ions, which enabled the presence of hydroxylated and
      deacetylated metabolites of taxol to be established.

PMID- 8759327
TI  - The novel selected-ion flow tube approach to trace gas analysis of air and
      breath.
AB  - We present an overview of the development and use of our selected-ion flow tube
      (SIFT) technique as a sensitive, quantitative method for the rapid, real-time
      analysis of the trace gas content of atmospheric air and human breath, presenting
      some pilot data from various research areas in which this method will find
      valuable application. We show that it is capable of detecting and quantifying
      trace gases, in complex mixtures such as breath, which are present at partial
      pressures down to about 10 parts per billion. Following discussions of the
      principles involved in this SIFT method of analysis, of the experiments which we
      have carried out to establish its quantitative validity, and of the air and
      breath sampling techniques involved, we present sample data on the detection and
      quantification of trace gases on the breath of healthy people and of patients
      suffering from renal failure and diabetes. We also show how breath ammonia can be
      accurately quantified from a single breath exhalation and used as an indicator of
      the presence in the stomach of the bacterium Helicobacter pylori. Health and
      safety applications are exemplified by analyses of the gases of the gases of
      cigarette smoke and on the breath of smokers. The value of this analytical method
      in environmental science is demonstrated by the analyses of petrol vapour, car
      exhaust emissions and the trace organic vapours detected in town air near a busy
      road. Final examples of the value of this analytical method are the detection and
      quantification of the gases emitted from crushed garlic and from breath following
      the chewing of a mint, which demonstrate its potential in food and flavour
      research. Throughout the paper we stress the advantages of this SIFT method
      compared to conventional mass spectrometry for trace gas analysis of complex
      mixtures, emphasizing its selectivity, sensitivity and real-time analysis
      capability. Finally, we note that whilst the current SIFT is strictly laboratory
      based, both transportable and portable instruments are under construction and
      development. These instruments will surely extend the application of this
      analytical technique into more areas and allow greater exploitation of their on
      line and real-time features.

PMID- 8759328
TI  - Post-source decay and delayed extraction in matrix-assisted laser
      desorption/ionization-reflectron time-of-flight mass spectrometry. Are there
      trade-offs?
AB  - By the incorporation of delayed extraction (DE) into matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry a dramatic improvement of
      performance with respect to sensitivity, mass resolution and mass accuracy of
      precursor ions up to approximately 10 kDa has been achieved. Since DE reduces
      collisional in-source activation to a large extent, the rate of subsequent
      metastable decay is considerably reduced. Results are presented which demonstrate
      that under DE the loss of total post-source decay (PSD) fragment ion yield can be
      as large as one order of magnitude but that, in terms of sensitivity, part of
      this loss is balanced by a better S/N ratio which results from a significantly
      improved mass resolution of the PSD fragment ions (M/delta M up to 1800 compared
      with M/delta M = 200-500 under prompt extraction). While this compensatory effect
      is true for the middle to high mass range of PSD fragment ions, it gradually
      vanishes towards the low mass end of the PSD mass scale where, in the case of
      linear peptides some important information (immonium ions) is lost. It appears,
      however, that in the majority of practical PSD work, DE improves the qualty of
      the PSD spectra and that high energy collisional post-source activation can
      compensate for the occasional loss of analytical information.

PMID- 8759329
TI  - The development of a data system for a combination of liquid chromatography or
      capillary electrophoresis with an ion trap storage/reflectron time-of-flight mass
      detector.
AB  - A data system based upon a 200 MHz transient recorder interface card in a Pentium
      PC computer is demonstrated for on-line analysis of microbore high-performance
      liquid chromatography (HPLC), capillary HPLC and capillary electrophoresis (CE)
      separations using a fast and sensitive ion-trap storage/reflectron time-of-flight
      mass spectrometric detector (IT-reTOFMS). Under the control of a user-written
      program, the system is capable of conducting the data acquisition and storage for
      a minimum of 30 min, at rates exceeding 10 Hz, of individual mass spectra
      containing 16,000 data points having 10 nsec resolution. The capability is mainly
      attributed to the use of a data reduction scheme in which only mass intensities
      higher than a preset threshold are saved as indexed flight-time/intensity pairs.
      This produces a typical reduction ratio of 30:1 in data set size, yielding faster
      storage with smaller file size, and permits the complete set of mass spectra to
      be held in the computer's memory. In addition, the data system is capable of
      displaying, for real-time evaluation of the analysis, each individual mass
      spectrum and the total-ion chromatogram. Further, the selected-ion chromatograms
      of given masses and a 3-dimensional topographic map describing a separation
      process can be rapidly generated from the collected data for the unambiguous and
      high fidelity identification of target analytes in a complex mixture.

PMID- 8759330
TI  - A quantitative study of in vitro hepatic metabolism of tacrolimus (FK506) using
      secondary ion and matrix-assisted laser desorption/ionization mass spectrometry.
AB  - The identification and simultaneous quantification of Tacrolimus and its hepatic
      metabolites in baboons has been achieved using matrix-assisted laser
      desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry and static
      secondary-ion mass spectrometry (TOF-SIMS). Little fragmentation, high
      sensitivity and tolerance to contamination are the major advantages of these
      methods, allowing facile identification and quantification of metabolites
      produced in vitro with minor analyte isolation. Based on the MALDI and TOF-SIMS
      results, seven metabolites have been identified: de-methylated, di de-methylated,
      hydroxylated, di hydroxylated, de-methylated hydroxylated, dihydrodiol, and di de
      methylated hydroxylated. The concentrations of the parent drug and its major
      metabolites (e.g. de-methylated, di de-methylated) were measured using Rapamycin
      as an internal standard. The time course of Tacrolimus and its major metabolites
      as a function of incubation time was calculated. Good correlation between SIMS
      and MALDI results was obtained.

PMID- 8759331
TI  - Determination of bacterial protein profiles by matrix-assisted laser
      desorption/ionization mass spectrometry with high-performance liquid
      chromatography.
AB  - A rapid method for profiling bacterial and cellular proteins has been developed
      using a combination of capillary high-performance liquid chromatography
      separation followed by (MALDI-MS) matrix-assisted laser desorption/ionization
      mass spectrometric analysis. In this method, bacteria are sonicated, the cell
      walls broken, and the water-soluble proteins precipitated for analysis. The
      proteins are separated by capillary liquid chromatography and detected on-line by
      a UV absorption detector. The eluents are then collected for off-line analysis by
      MALDI-MS. Using this method, it is demonstrated that bacteria can be
      discriminated based upon their protein profiles to the species level with only
      pmol level detection of proteins. It has also proved to be a fast and accurate
      means for monitoring the expression of Hsp27 in an insect cell system.

PMID- 8759332
TI  - Rapid identification of intact whole bacteria based on spectral patterns using
      matrix-assisted laser desorption/ionization with time-of-flight mass
      spectrometry.
AB  - Matrix assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOFMS) was investigated as a method for the rapid identification of whole
      bacteria, either by comparison with archived reference spectra or by co-analysis
      with cultures of known bacteria. Bacteria were sampled from colonies on an agar
      plate, mixed with the matrix, air-dried, and introduced in batches into the mass
      spectrometer for analysis. In the first experiment, both bacterial strains that
      had been previously analyzed to obtain reference spectra and other strains that
      had not been analyzed were blind-numbered and their spectra were obtained. Those
      strains that matched reference spectra were found to be correctly identified. A
      second experiment involved co-analysis of reference strains and bind-numbered
      strains under identical conditions; species-specific identification was
      demonstrated by comparison of spectra of the blind-numbered strains with those of
      the standards. In all of the spectra obtained in these experiments, each
      bacterial strain showed a few characteristic high-mass ions which are thought to
      be derived from bacterial proteins. This work represents the first reported
      instance of successful bacterial chemotaxonomy by MALDI-TOFMS analysis of whole
      cells. For the strains tested, the method is rapid and simple.

PMID- 8759333
TI  - Curie-point pyrolysis-gas chromatography/mass spectrometry in the art field. 2-
      The characterization of proteinaceous binders.
AB  - Curie point pyrolysis with gas chromatography/mass spectrometry has been employed
      to characterize some proteinaceous media used in the art field as painting
      binders: milk casein, egg yolk, egg albumin, bone glue, skin glue, rabbit glue
      and fish glue. A careful analysis of the gas chromatograms so obtained has led to
      the distinction of the different proteinaceous binders in terms of different
      chromatographic profiles. Some of the pyrolysis products have been identified by
      library search.

PMID- 8759334
TI  - A comparison of the positive- and negative-ion mass spectra of bio-active
      peptides from the dorsal secretion of the Australian red tree frog, Litoria
      rubella.
AB  - The collision-induced tandem mass spectral data for MH+ and [M-H]- ions from six
      bio-active peptides from Litoria rubella are compared. Backbone cleavages of [M
      H]- ions provide sequencing information for five of the peptides [e.g. Phe Pro
      Trp Leu (NH2) and pGlu Phe Pro Trp Leu (NH2)] and in these cases, the negative
      ion spectra are as informative as the positive-ion spectra. Side-chain cleavages
      are also noted in these spectra. For example, (i) when Trp is present, the loss
      of C9H7N (129 u) competes with the backbone cleavages, and (ii) the [M-H]- ion of
      Ile Glu Phe Phe Thr (NH2) undergoes facile side-chain fragmentation [loss of H2O
      (from Glu) and MeCHO (from Thr)], but does not form any conventional backbone
      cleavage ions.

PMID- 8759335
TI  - Simple analysis of plasmalogens in erythrocytes using gas chromatography/mass
      spectrometry with selected-ion monitoring acquisition.
AB  - Plasmalogens are a unique class of ether-phospholipids whose role, even though
      not fully defined, is essential. Their biosynthesis starts in peroxisomes,
      therefore, plasmalogen analysis is fundamental in the study of peroxisomal
      disorders. The present work reports a simple method for plasmalogen determination
      in erythrocytes for use in the study of peroxisomal disorders in humans; the
      procedure is based on two other methods that have previously been reported and
      employs GC/MS for separation and detection.

PMID- 8759336
TI  - Electron impact mass spectrometry of some potential anti-HIV nucleosides.

PMID- 8759337
TI  - Absence of cellular responses to a putative autoantigen in onchocercal
      chorioretinopathy: cellular autoimmunity in onchocercal chorioretinopathy.

PMID- 8759338
TI  - Recent developments in vision research: light damage in cataract.

PMID- 8759339
TI  - Presence of functional type B natriuretic peptide receptor in human ocular cells.
AB  - PURPOSE: To study the effects of natriuretic peptides on cyclic guanosine
      monophosphate (cGMP) production and calcium mobilization in cultured human ocular
      cells. METHODS: Cultured simian virus 40-transformed (HTM-3) and nontransformed
      (HTM-16) human trabecular meshwork (TM) cells and nontransformed human ciliary
      muscle (CM) cells were used. Accumulation of cGMP in cells lysate was measured by
      radioimmunoassay. Intracellular calcium concentration was measured by microscope
      based ratiofluorometry. RESULTS: Both atrial natriuretic peptide (ANP) and C-type
      natriuretic peptide (CNP) increased the accumulation of cGMP in HTM-3, HTM-16,
      and CM cells. In the nontransformed TM cells, CNP was five times more efficacious
      (maximal effect of CNP was 497% +/- 44% that of ANP) and 10 times more potent
      than ANP (ANP, log [EC50] = -6.99 +/- 0.08; CNP, log [EC50] = -7.96 +/- 0.20).
      Similar results were seen in HTM-3 and CM cells. Under the assay conditions used,
      the peptides increased only the production of cGMP without changing its
      degradation rate. The peptide-induced increase of cGMP in the TM and CM cells
      correlated with suppression of carbachol-induced calcium mobilization in the
      cell. CONCLUSIONS: It is known that CNP, but not ANP, selectively activates the
      guanylyl cyclase associated with the type B natriuretic peptide receptor (NPR-B).
      Thus, the data suggest that NPR-B is the primary functional NPR in the TM and CM
      cells. The effects on cGMP and calcium produced by the activation of this
      receptor are expected to alter TM and CM contractility and may affect aqueous
      humor hydrodynamics and intraocular pressure.

PMID- 8759340
TI  - Orbicularis oculi muscle fibers are relatively short and heterogeneous in length.
AB  - PURPOSE: The anatomy of individual myofibers within the orbicularis oculi muscle
      was examined to determine individual myofiber lengths in the different regions of
      the muscle. A wide variety of eyelid conditions require eyelid surgery or drug
      injections directly into the eyelid. Knowledge of regional myofiber anatomy and
      physiology is important for accurate treatment of these conditions. METHODS:
      Eyelid specimens from rabbits were treated with collagenase, fixed, and stained
      for neuromuscular junction location. Individual myofibers were dissected from
      these muscle specimens and were measured to determine individual myofiber length
      and neuromuscular junction position. Additional eyelid specimens of rabbits and
      humans were stained en bloc to visualize neuromuscular junction location in the
      pretarsal and preseptal regions of the orbicularis oculi muscle. RESULTS: The
      myofibers showed variable lengths, shorter in the pretarsal region of the muscle
      and longer in the preseptal region. The average individual myofiber length in the
      pretarsal region was 36% as long as the entire length of the pretarsal muscle
      region. In the preseptal region, the myofibers were slightly longer, covering 54%
      of the entire length of this region of the muscle. In both the pretarsal and
      preseptal regions of the rabbit and human orbicularis oculi muscle, there were
      many clusters of neuromuscular junctions throughout the medial to lateral length
      of the muscle, with the majority of the neuromuscular junctions in the medial and
      lateral canthal regions of the preseptal portion of the lid. This indicates that
      the muscle is composed of relatively short, overlapping myofibers, and that the
      shortest myofibers reside in the medial and lateral canthal regions of the
      eyelid. Multiple innervation of one rabbit myofiber was observed as a rare
      occurrence. CONCLUSIONS: Individual myofibers of the orbicularis oculi muscle are
      relatively short, end intrafascicularly, and are of heterogeneous lengths varying
      regionally within the muscle. Thus, for drug injections into the eyelid, optimal
      drug effectiveness may require treatment of the entire lid from medial to lateral
      canthus to overcome the tissue barriers to diffusion. The existence of muscle
      fibers of heterogeneous lengths suggests that the complex organization of muscle
      fibers may play previously unappreciated but important roles in normal function,
      pathophysiology, and age-related changes in the eyelid.

PMID- 8759341
TI  - Immunodetection of connexins and cadherins in corneal fibroblasts and
      myofibroblasts.
AB  - PURPOSE: In normal cornea, stromal fibroblasts (keratocytes) interact with one
      another by gap junctions. After corneal wounding, the remaining corneal stroma
      cells are phenotypically fibroblasts and myofibroblasts. For insight into the
      respective roles of fibroblasts and myofibroblasts in wound healing, the authors
      have investigated the molecular basis of cell-cell interaction in cultures of
      corneal fibroblasts and corneal myofibroblasts. METHODS: Using Western blot
      analysis and immunofluorescent microscopy, the authors determined the relative
      expression and localization of junction proteins-connexins, cadherins, and
      cadherin-associated proteins (catenins)-in cultured fibroblasts and
      myofibroblasts. RESULTS: In cultured corneal fibroblasts, the gap junction
      protein, connexin 43, was highly expressed and was localized to dense maculae;
      cadherins were not detected in cell-cell contacts. Cultured myofibroblasts showed
      the opposite pattern: Cadherins were highly expressed and localized at the cell
      cell contacts, whereas myofibroblast connexin 43 was primarily intracellular.
      Myofibroblast cadherin was identified by a pan-cadherin antibody as a molecule of
      135 kDa that reacted weakly with an N-cadherin monoclonal antibody. In addition,
      cadherin-associated cytoplasmic proteins, alpha- and beta-catenins, co-localized
      with cadherin at the cell-cell borders of the myofibroblasts. CONCLUSIONS: The
      presence of connexin 43 at the cell-cell borders of corneal fibroblasts is
      consistent with a primary communication role of junctions in confluent corneal
      fibroblasts. In contrast, the presence of cadherin at the cell-cel borders of
      myofibroblasts may provide a site for insertion of actin filaments. A cadherin
      actin association could support actin-based force generation for effective wound
      closure.

PMID- 8759342
TI  - Human corneal fibrillogenesis. Collagen V structural analysis and fibrillar
      assembly by stromal fibroblasts in culture.
AB  - PURPOSE: The stroma of the developing cornea is a highly organized extracellular
      matrix formed essentially by uniform, small-diameter collagen fibrils with
      constant interfibrillar spacing. Unlike the fibrillogenesis of chicken cornea,
      the assembly and maturation of human corneal fibrils have been poorly
      investigated. In the current study, the authors aimed to ascertain the
      heterotypic organization (collagens I and V) of the human corneal fibrils at the
      supramolecular level. To gain more insight into the molecular structure of
      collagen V, its cellular source, and its role in fibrillogenesis, the authors
      used cultured human corneal fibroblasts. METHODS: The structure of human corneal
      stroma after brief homogenization of the tissue was analyzed by immunogold
      labeling using specific polyclonal antibodies and rotary shadowing. Biochemical,
      electron microscopic, and immunolabeling approaches were used to investigate the
      collagen fibril formation and the extracellular matrix synthesis using human
      corneal fibroblasts grown in culture as a model system. RESULTS: The authors
      showed that in human corneal stroma, collagen I is distributed uniformly along
      the striated fibrils, in contrast to collagen V, which could be identified only
      at sites at which the fibrils partially were disrupted. Rotary shadowing
      observations of the homogenate revealed that collagen VI, a major component of
      the human cornea, was associated closely with the collagen fibril surface.
      Corneal fibroblasts synthesize and deposit a collagenous matrix with fibrils
      resembling those of the human cornea in appearance and collagen composition.
      Biochemical data indicate that a high concentration (20% to 30%) of collagen V is
      synthesized by stromal fibroblasts and that collagen V molecules are processed
      similarly to matrix forms in which the extension peptides are retained on the
      molecules. CONCLUSIONS: The heterotypic nature (collagens I and V) of human
      corneal fibrils was determined. Results indicate that human corneal fibroblasts
      synthesize the major collagen types in human cornea (collagens I, V, and VI) and
      express all the posttranslational equipment for correct collagen molecular
      assembly and processing in a manner that closely resembles the situation in situ,
      offering the opportunity for more detailed study of this process, which is
      essential for optical transparency.

PMID- 8759343
TI  - Innervation of the chick cornea analyzed in vitro.
AB  - PURPOSE: During the early stages (embryonic day 3 [E3]) of avian corneal
      development, nerve fibers extend from the trigeminal ganglion to the corneal
      limbus. On E11, these nerve fibers enter the cornea and extend through the
      secondary stroma to begin innervation of the epithelium on E13. This process of
      innervation is concomitant with the cornea's dehydration and transition from
      opacity to transparency; thus, suggesting a link between innervation and the
      attainment of corneal function. This investigation attempts to ascertain whether
      the developing cornea can support its innervation in vitro and whether there is a
      possible developmental interrelationship between corneal innervation and
      dehydration, with the associated transition from opacity to transparency.
      METHODS: Isolated corneas from either E8 or E14 chicks were co-cultured with E8
      dorsal root ganglia. After 4 days of culture, innervation was visualized by
      silver staining and immunohistochemistry. Changes in corneal composition and
      organization associated with this innervation in vitro were analyzed by measuring
      changes in specific hydration, thickness and compaction, and incorporation of
      [35S]sulfate into glycosaminoglycans during co-culture. RESULTS: The E8 and E14
      corneas support extensive innervation in vitro. Developing nerve fibers extend
      through the secondary stroma to innervate the epithelium. In vitro innervation of
      E8, but not E14, corneas was associated with a decrease in corneal specific
      hydration, whereas control corneas (without dorsal root ganglia) failed to show
      any such changes. E8 corneas also showed a significant increase in compaction
      when innervated in vitro. Corneal innervation in vitro did not significantly
      change the overall incorporation of [35S]sulfate into glycosaminoglycans.
      Furthermore, incorporation of [35S]sulfate into corneal sulfated
      glycosaminoglycans (sGAG) is not influenced by either the number of nerve fibers
      innervating the cornea or nerve growth factor (NGF). In addition, the
      distribution of staining of the corneal glycosaminoglycans, chondroitin sulfate
      and keratan sulfate, and peanut agglutinin-binding epitopes, suggests that these
      molecules are not associated with inhibition of axonal development. CONCLUSIONS:
      The in vitro system described here is a useful model to understand the process of
      corneal development. Co-culture has shown that corneal innervation promotes the
      process of dehydration, which is dependent on the age of the cornea. However,
      other functionally related refinements necessary for transparency-notably
      proteoglycan synthesis-may not be linked to innervation or NGF production. The
      authors conclude that the development of transparency is dependent on corneal
      innervation, though not exclusively, and that other controlling factors also are
      required.

PMID- 8759344
TI  - Sub-retinal pigment epithelial deposits in a dominant late-onset retinal
      degeneration.
AB  - PURPOSE: To determine the pathogenesis of an autosomal dominant late-onset
      retinal degeneration by studies of the retinal histopathology, phenotype of
      family members, and candidate genes for the disease. METHODS: The retina from an
      80-year-old patient donor was prepared for light and electron microscopy,
      including special stains and immunocytochemistry. Family members were examined
      clinically and with retinal function tests. Rhodopsin, peripherin/RDS, and TIMP3
      genes were screened for mutations, and linkage analysis was performed with short
      tandem repeat polymorphisms flanking these genes. RESULTS: Affected family
      members had nyctalopia in the sixth decade of life and severe visual loss
      developed by the eighth decade. The donor retina showed marked loss of
      photoreceptors except in the inferior periphery. A thick layer of extracellular
      deposits was present between the RPE and Bruch's membrane in all retinal regions.
      A 70-year-old affected family member had a retinopathy resembling retinitis
      pigmentosa. Her 42-year-old daughter had a patch of punctate yellow-white lesions
      in one fundus and abnormal dark adaptation. The 50-year-old son of the donor had
      normal fundi but abnormal dark adaptation and electroretinography. No mutations
      were detected in the coding sequence of the rhodopsin, peripherin/RDS, and TIMP3
      genes. Rhodopsin and TIMP3 were further excluded with linkage analysis.
      CONCLUSIONS: This novel retinal degeneration shares histopathologic and clinical
      features with both Sorsby fundus dystrophy and retinitis pigmentosa. The sub-RPE
      deposits may disrupt the exchange of nutrients and metabolites between the retina
      and the choriocapillaris, leading to photoreceptor dysfunction and degeneration.

PMID- 8759345
TI  - Visual evoked potentials with crossed asymmetry in incomplete congenital
      stationary night blindness.
AB  - PURPOSE: To investigate a proposed postretinal defect in patients with the
      incomplete form of congenital stationary night blindness (CSNB2) and to compare
      visual evoked potential (VEP) results with those found in various forms of
      albinism. METHODS: Visual evoked potentials were performed in 10 patients with a
      diagnosis of CSNB2, 10 subjects with albinism, and 17 normal subjects. Visual
      evoked potentials were elicited monocularly with diffuse flash stimulation. Scalp
      electrodes were placed over each hemisphere and referred to the forehead.
      Interhemispheric bipolar recordings were derived, and the correlation coefficient
      (CC) was calculated for various segments of the interhemispheric responses.
      RESULTS: A crossed visual evoked potential asymmetry pattern could be
      demonstrated in 9 of 10 patients with CSNB2. All subjects with albinism and none
      of the normal subjects showed the crossed asymmetry pattern. Statistical
      comparison of the CC computed for various segments of the interhemispheric
      response shows that the pattern of inversion in CSNB2 is more prominent in the 25
      to 100 msec range (median CC, -0.37) and in the 175 to 250 msec range (CC, 
      0.27). In subjects with albinism, all segments show a negative CC (range, -0.46
      to -0.60). In normal subjects, all segments are positively correlated (range,
      0.36 to 0.66). CONCLUSIONS: Crossed visual evoked potential asymmetry was found
      in patients with CSNB2; therefore, excessive decussation, as demonstrated by this
      testing procedure, should not be considered as pathognomonic for albinism.

PMID- 8759346
TI  - Tissue transglutaminase in apoptosis of photoreceptor cells in rat retina.
AB  - PURPOSE: The possible involvement of tissue transglutaminase (tTG) in apoptosis
      during photoreceptor degeneration was examined in retinal photic injury in rats
      and in retinal dystrophy of Royal College of Surgeons (RCS) rats. METHODS:
      Retinal photic injury was induced in 48 male Lewis albino rats by exposure to
      green fluorescent light of 300 to 320 foot-candles. The retinal tTG was examined
      by enzyme assay, immunohistochemistry, and Western blot analysis after 9, 12, or
      24 hours of exposure or at 6 or 24 hours of dark adaptation after 24 hours of
      light exposure. Retinas from RCS rats at various stages of degeneration also were
      examined with similar methods. RESULTS: There was a progressive increase in
      retinal tTG activity after 300 to 320 ft-c of light exposure, reaching a peak
      after 24 hours of light exposure. In the RCS rats, tTG activity increased with
      age. Western blot analysis revealed an immunoreactive band at 80 kDa, which
      increased in accordance with the transglutaminase activity in both models. In
      normal rat retinas, tTG immunolabeling was present only in the outer segments.
      There was an increased number of immunolabeled photoreceptor nuclei from 12 hours
      of light exposure to 24 hours of light exposure. In the RCS rat, increasing
      numbers of immunopositive photoreceptor nuclei from 20 to 50 days of age were
      noted. CONCLUSIONS: The data associated increased retinal tTG activity and enzyme
      levels with photoreceptor cells undergoing apoptosis. The tTG-dependent
      irreversible cross-linking of intracellular protein may play an important role in
      causing the structural changes in cells undergoing apoptosis in the retina.

PMID- 8759347
TI  - A gene expression profile of human corneal epithelium and the isolation of human
      keratin 12 cDNA.
AB  - PURPOSE: To describe the quantitative and qualitative aspects of gene expression
      in human corneal epithelium and to discover novel cornea-specific genes. METHODS:
      A 3'-directed cDNA library was constructed with messenger RNA prepared from
      normal human corneal epithelial cells, and inserts in 1069 randomly chosen clones
      were sequenced. These sequences were compared with each other to determine the
      frequency of appearance and were searched against GenBank for identification. The
      resultant expression profile, a list of gene species and their recurrences,
      reflected the composition of mRNA in the cornea. Recurrently appearing sequences,
      representing abundant transcripts, were compared with sequences in expression
      profiles obtained from seven other tissues and from those in dbEST to discover
      cornea-specific genes. RESULTS: The expression profile of human corneal
      epithelium showed that the most abundant transcript in this tissue was that for
      apolipoprotein J. Altogether 62 genes were suggested to be very active, including
      calcyclin, alpha-enolase, keratin 3, connexin 43, and 12 novel genes. The
      expression of four of these 12 novel genes seemed to be limited to cornea because
      they were not found in seven other expression profiles nor in dbEST. Full-length
      cDNA corresponding to one of these (GS8025), isolated from a separately made cDNA
      library, contained open reading frame highly homologous to mouse keratin 12,
      which is known to be cornea specific. CONCLUSIONS: An expression profile of
      corneal epithelium provides probes to monitor physiological and pathologic
      conditions of this tissue in terms of gene expression. Furthermore, by comparing
      this profile with those of other tissues, probes to isolate genes uniquely
      transcribed in corneal epithelium are determined. These genes are assumed to
      carry unique functions for this tissue and are candidate genes for inherited
      diseases that manifest only in cornea. As an example, human cornea-specific
      keratin was isolated, and partial cDNA sequences for three more cornea-specific
      genes were presented.

PMID- 8759348
TI  - Effect of photorefractive keratectomy on the accuracy of pneumatonometer readings
      in rabbits.
AB  - PURPOSE: To determine whether measurement of intraocular pressure (IOP) using a
      pneumatonometer is reliable after myopic 5 or 15 D excimer laser photoablation in
      rabbits. METHODS: Ten rabbits underwent 5 D myopic photorefractive keratectomy
      (PRK) of the left eye. Another seven rabbits underwent 15 D PRK: The right eye
      served as a control. The diameter of each PRK was 5 mm. Rabbits were examined 2.5
      to 3 months later under general anesthesia. Eyes were cannulated, and the IOP was
      maintained at 5 to 40 mm Hg and measured using an intracameral manometer and a
      pneumatonometer at each pressure level; approximately 50 pressure points were
      formed. Readings of the two techniques were compared. RESULTS: Linear regression
      analysis comparing manometric and pneumatonometric readings revealed the
      following data in eyes with 5 D corrections (n = 10): correlation coefficient (r)
      = 0.926, slope = 1.058, and intercept = -3.133. The values of the unoperated
      control eyes were: r = 0.900, slope = 0.962, and intercept = -1.010. The
      following results were obtained in eyes with 15 D photoablation (n = 7): r =
      0.876, slope 1.133, and intercept -3.147. Values for the control eye were: r =
      0.885, slope = 1.175, and intercept = -3.497. When the manometer and
      pneumatonometer readings of all animals were compared, the adjusted squared
      correlation coefficient was 79%. When the variabilities associated with the
      animals and the PRK procedure (pooled 5 and 15 D corrections) were taken into
      account, adjusted squared correlation coefficient increased from 8% to 87%.
      CONCLUSIONS: Photorefractive keratectomy as high as 15 D/5 mm had only a minor
      effect on pneumatonometer readings in rabbits, indicating that the elastic
      properties of the cornea related to the accuracy of pneumatonometry were not
      significantly altered. Postoperative IOP monitoring with tonometers, based on
      flattening of the cornea under pressure, is accurate after PRK.

PMID- 8759349
TI  - Cell lineage and the differentiation of corneal epithelial cells.
AB  - PURPOSE: Studies were designed to determine whether cell division and cell
      differentiation are linked directly in the corneal epithelium. To obtain these
      data, corneal basal epithelial cells were labeled during DNA synthesis, and the
      resultant daughter cells were followed for as long as 2 weeks. METHODS: Adult
      rats were injected with 5-bromo-deoxyuridine (BrdU), a thymidine analog, and were
      killed 6 hours to 14 days later. Corneas were fixed and permeabilized, and BrdU
      labeled nuclei were detected with a monoclonal antibody to BrdU and a fluorescent
      labeled secondary antibody. Fluorescent nuclei were visualized in three
      dimensions in corneal whole-mounts using a laser scanning confocal microscope.
      Optical sections were collected and displayed as serial images, three-dimensional
      anaglyphs, color-encoded projections, or three-dimensional reconstructions. Data
      were confirmed using 3H-thymidine autoradiography of epithelia sectioned parallel
      to the corneal surface. RESULTS: Cells synthesizing DNA at the time of injection
      incorporated BrdU into their DNA. Pairs of labeled nuclei were produced by the
      division of cells that had been labeled with BrdU. These daughter cells remained
      in the basal layer of the epithelium for a variable period of time. Some daughter
      cells continued to divide, producing clusters of labeled basal cells. When
      labeled daughter cells left the basal layer and began the process of terminal
      differentiation, they nearly always did so together. The synchronous
      differentiation of daughter cells was evident from the pairs of labeled nuclei
      seen throughout the depth of the epithelium from 2 to 14 days after labeling.
      CONCLUSIONS: Cell division and differentiation are not linked directly in the
      corneal epithelium. After cell division, daughter cells either remain in the
      basal layer, where they may undergo additional rounds of cell division, or both
      cells differentiate synchronously. When the daughter cells of a mitosis
      differentiate, the time between the previous cell division and differentiation is
      highly variable. This suggests that the coordination of cell division and
      differentiation in the corneal epithelium involves a complex regulatory network.

PMID- 8759350
TI  - Synthesis of group II phospholipase A2 and lysozyme in lacrimal glands.
AB  - PURPOSE: The aim of this study was to demonstrate the synthesis and cellular
      distribution of group II phospholipase A2 and lysozyme in the main and accessory
      lacrimal glands. METHODS: The authors studied samples of normal main lacrimal
      glands of seven autopsied subjects and accessory lacrimal glands of eight
      patients who underwent ptosis surgery. The specimens were immunostained with a
      rabbit antiserum against group II phospholipase A2 and a monoclonal antibody
      against lysozyme. Expression of group II phospholipase A2 gene was shown using
      Northern hybridization and in situ hybridization. RESULTS: Lysozyme was present
      in the secretory granules of most acini, whereas group II phospholipase A2 was
      seen in a minority of acinar cells, primarily in the central parts of lobules in
      the main and accessory lacrimal glands. Synthesis of group II phospholipase A2 in
      the glandular cells was confirmed by Northern hybridization and by in situ
      hybridization. CONCLUSIONS: There are two specialized cell types in the main and
      accessory lacrimal glands, one synthesizing group II phospholipase A2 and the
      other synthesizing lysozyme. These enzymes are important nonspecific
      antibacterial factors in tears.

PMID- 8759351
TI  - Characterization of ocular hypertension induced by adenosine agonists.
AB  - PURPOSE: Previous studies have shown that adenosine agonists may induce a rise in
      intraocular pressure (IOP), a reduction in IOP, or both. Although the reduction
      in IOP results from the activation of adenosine A1 receptors, the mechanisms
      responsible for the rise in IOP have not been investigated. This study examines
      the receptors and mechanisms responsible for the adenosine agonist-induced rise
      in IOP. METHODS: The ocular effects of the nonselective adenosine agonist NECA,
      the relatively selective adenosine A2 agonist CV-1808, the A2a agonist CGS-21680,
      and the A1 agonist R-PIA were evaluated. RESULTS: The topical administration of
      CV-1808 produced a rapid rise in IOP, with a maximum increase of 15.6 +/- 1.6 mm
      Hg. Dose-response curves demonstrated that each agonist produced a dose-related
      rise in IOP with the following rank order of potency: NECA > CV-1808 > > R-PIA =
      CGS-21680. At times corresponding to the rise in IOP, the administration of high
      doses of CV-1808 (165 micrograms) produced a significant increase in aqueous
      humor flow and protein concentration. Increases in IOP and aqueous humor protein
      levels induced by CV-1808 were blocked by pretreatment with the adenosine A2
      antagonist DMPX. In vitro studies demonstrated that CV-1808 did not alter cyclic
      adenosine monophosphate production in the rabbit iris-ciliary body. In cats,
      topical administration of CV-1808 produced a rapid rise in IOP, with a maximum
      increase of 8.1 +/- 2.4 mm Hg and an ED50 of 73 +/- 2.9 micrograms. This rise in
      IOP was blocked by DMPX pretreatment. CONCLUSIONS: These data demonstrate that
      adenosine receptor agonists can induce an acute rise in IOP in rabbits and cats.
      On the basis of pharmacologic characteristics, the rise in IOP is consistent with
      the activation of ocular adenosine A2 receptors. Functional studies indicate that
      at high doses, this rise in IOP involves an increase in aqueous flow and the
      breakdown of the blood-aqueous barrier.

PMID- 8759352
TI  - Serum effects on aqueous outflow during anterior chamber perfusion in monkeys.
AB  - PURPOSE: To prevent the increase in outflow facility during anterior chamber
      perfusion in nonhuman primates by the addition of autologous serum to Barany's
      mock aqueous humor. METHODS: Total outflow facility was measured simultaneously
      in both eyes of living cynomolgus monkeys for 3 hours by two-level constant
      pressure perfusion of the anterior chambers from elevated reservoirs with
      Barany's solution with (one eye) or without (opposite eye) 3%, 5%, 10%, or 15% to
      20% autologous serum. In other experiments, the anterior chamber contents
      initially were exchanged with Barany's solution with (one eye) or without
      (opposite eye) 5% autologous serum, and the facility response to intravenous
      pilocarpine was determined. RESULTS: Eyes perfused with serum had a lower
      starting facility than control eyes, with facility decreasing with increasing
      serum concentrations. For both groups, facility increased with perfusion time and
      with volume of fluid perfused through the eye, but the rate of change of facility
      over time and per change in volume was significantly less for the serum-treated
      eyes. This difference remained significant when the proportional change of
      facility relative to baseline level was analyzed as a function of time but not as
      a function of volume. Intravenous infusion of pilocarpine increased facility by
      approximately the same proportion relative to baseline in both groups, but the
      absolute change and the final facility were lower in the serum-treated eyes.
      CONCLUSIONS: Serum or a serum component in the vicinity of the trabecular
      meshwork normally may help maintain outflow resistance but may be washed away
      during perfusion with serum-free media.

PMID- 8759353
TI  - Effect of age on superoxide dismutase activity of human trabecular meshwork.
AB  - PURPOSE: It has been hypothesized that accelerated aging of the trabecular
      meshwork, perhaps because of oxidative damage, is involved in the pathogenesis of
      primary open angle glaucoma. The authors sought to evaluate the effect of donor
      age on the specific activity of superoxide dismutase and catalase in normal fresh
      human cadaver trabecular meshwork. METHODS: Total superoxide dismutase and
      catalase were assayed in tissue extracts generated from fresh human trabecular
      meshwork. Cadaver tissue was obtained from 19 donors (18 paired) of a wide age
      range (30 to 91 years). The assays were performed within 6 hours of enucleation
      and within 36 hours of donor death. Enzyme-specific activities were calculated
      using protein concentration of the extract as the denominator. RESULTS: Multiple
      regression analysis modeled with age and time from death until the beginning of
      the experiment was performed. The specific activity of superoxide dismutase
      declined with age (P = 0.00022; r2 = 0.67). There was no effect of age on
      catalase specific activity (P = 0.24; r2 = 0.16). The time from donor death until
      the beginning of the experiment was not a significant factor (P > 0.28).
      CONCLUSIONS: The specific activity of superoxide dismutase, but not catalase,
      demonstrates an age-dependent decline in normal cadaver human trabecular
      meshwork. The potential role of superoxide dismutase in primary open angle
      glaucoma, a disorder of the aging trabecular meshwork, warrants further
      investigation.

PMID- 8759354
TI  - Comparative flow velocity of erythrocytes and leukocytes in feline retinal
      capillaries.
AB  - PURPOSE: To study the flow velocity of erythrocytes and leukocytes in the same
      retinal capillaries in cat eyes. METHODS: Blood cells from cats were stained with
      fluorescent label and reinjected into the animals. An electro-optical device
      combined with a highly sensitive CCD camera detected the fluorescent signal from
      the labeled blood cells. The signal was stored on a videotape (VHS-PAL, 25 frames
      per second) and later analyzed digitally. Twenty leukocytes were identified, each
      flowing through a separate retinal capillary pathway. The capillary pathways were
      categorized as simple and complex according to their morphologic complexity.
      Observations were made on 10 simple and 10 complex capillary pathways. The
      passages of one leukocyte and 20 erythrocytes in each capillary path were
      recorded and analyzed. The blood cell velocity ratio was calculated from the
      number of frames needed for each cell to complete a passage through the capillary
      pathway (higher velocity = fewer frames). RESULTS: The erythrocytes traveled
      faster than the leukocytes in both the short and long capillary pathways. The
      frames ratio (mean percent +/- standard deviation) of erythrocyte-leukocyte
      passage in the same capillary pathway was 84.55% +/- 2.0% in the short ones and
      66.21% +/- 7.1% in the complex ones. The main deceleration in leukocytes flow was
      noted in the looping parts of the complex capillary pathways. CONCLUSIONS: The
      velocity of leukocytes is slower than that of erythrocytes in a given retinal
      capillary pathway. The structural complexity of a capillary pathway has a greater
      effect on leukocytic velocity than on erythrocytic velocity.

PMID- 8759355
TI  - An endothelin-1 induced model of optic nerve ischemia in the rabbit.
AB  - PURPOSE: To evaluate blood flow reduction and topographic optic nerve changes
      after the local administration of endothelin-1 in vivo, delivered to the
      perineural region of the anterior optic nerve in the rabbit. METHODS: Endothelin
      1 (five rabbits) in a dosage of 0.1 microgram/day or balanced salt solution (two
      rabbits) was delivered to the perineural region of the anterior optic nerve with
      osmotically driven minipumps. Optic nerve blood flow was determined by the
      colored microspheres technique after 14 days of local endothelin-1 or balanced
      salt solution administration to the microvasculature of the optic nerve. In
      addition, optic nerve blood flow was determined in two rabbits that had no
      minipump implants. The morphologic changes induced by reduction of blood flow
      were assessed in five additional rabbits implanted with osmotically driven
      minipumps containing endothelin-1 (0.1 microgram/day). These rabbits were
      observed for 8 weeks, and the morphologic optic nerve changes were monitored with
      a confocal scanning laser ophthalmoscope. RESULTS: Independent of intraocular
      pressure, endothelin-1 induced a decrease in blood flow of approximately 38% in
      the experimental eye, compared to the decrease induced by balanced salt solution
      or to the decrease in rabbits without minipumps (analysis of covariance, P =
      0.0092). Multivariate statistical analysis showed a significant change in
      topometric parameters (cup area, cup depth, rim volume) obtained with a confocal
      scanning laser ophthalmoscope, indicating an increase in optic nerve cupping and
      a decrease of the perineural rim volume in the experimental eyes (P = 0.017).
      CONCLUSIONS: The current results suggest that morphologic optic nerve alterations
      can be induced experimentally in the rabbit model after ischemia produced by the
      local administration of endothelin-1 to the perineural region of the anterior
      optic nerve.

PMID- 8759356
TI  - Identification, quantitation, and purification of a 36 kDa circulating protein
      associated with active pars planitis.
AB  - PURPOSE: To establish a correlation between the presence of a 36 kDa protein in
      the blood of patients with pars planitis and to characterize and purify this
      protein. METHODS: Blood samples were obtained from patients with pars planitis
      and other types of uveitis and from various controls. Samples were treated with
      polyethelene glycol and protein A and were analyzed on 10% SDS-PAGE for the
      presence of a 36 kDa protein. Quantitative estimation of the level of this
      protein was determined by densitometric tracing of the stained gels. Polyclonal
      antibodies were raised by immunizing New Zealand White rabbits with a mixture of
      the gel fragment containing the 36 kDa protein (p-36) and complete Freund's
      adjuvant. These antibodies were used in the immunoaffinity purification of this
      protein. RESULTS: The levels of p-36 were sixfold to eightfold higher in 81% of
      the patients with active pars planitis than in controls (P < 0.05). Furthermore,
      the levels of this protein correlated with disease activity. A partial amino
      terminal sequence analysis revealed that p-36 may be a novel protein. It has been
      purified from the patient's blood using affinity chromatography. CONCLUSIONS: A
      36 kDa protein (p-36) is found in elevated concentrations in the blood of many
      patients with active pars planitis. Its putative role in the etiopathogenesis of
      pars planitis is unknown.

PMID- 8759358
TI  - Membrane-bound regulators of complement activation in uveal melanomas. CD46,
      CD55, and CD59 in uveal melanomas.
AB  - PURPOSE: To identify the presence of membrane-bound regulators of complement
      activation (m-RCA) on uveal melanomas and uveal melanoma cell lines and to
      examine their role in the inhibition of complement-mediated lysis in vitro.
      METHODS: Immunohistochemistry and flow cytometric analysis with monoclonal
      antibodies directed against m-RCA CD46, CD55, and CD59 were applied to tissue
      sections of 10 uveal melanomas, three primary uveal melanoma cell lines, and one
      uveal melanoma metastatic cell line. A microcytotoxicity test was used for
      measuring antibody-dependent complement-mediated lysis. RESULTS: The tissue
      sections and all four uveal melanoma cell lines expressed CD46, CD55, and CD59.
      Complement-mediated lysis in the presence of human complement was increased after
      partial removal of the m-RCA CD55 and CD59 with phosphatidylinositol-specific
      phospholipase C from the uveal melanoma cell line 92-1. CONCLUSIONS: These
      results demonstrate that CD46, CD55, and CD59 are expressed in uveal melanomas
      and that CD55 or CD59, or both, plays a role in resistance to complement-mediated
      cytotoxicity. The finding that m-RCA are expressed in uveal melanomas may have
      implications for the effectiveness of the anti-tumor response and in the
      therapeutic application of monoclonal antibodies directed against tumor
      associated antigens.

PMID- 8759357
TI  - Molecular cloning, sequencing, and expression of the 36 kDa protein present in
      pars planitis. Sequence homology with yeast nucleopore complex protein.
AB  - PURPOSE: Patients with active pars planitis have increased levels of a 36 kDa
      protein (p-36) in their circulation. The current studies were undertaken to
      determine the primary structure of this protein. METHODS: A degenerate
      oligonucleotide probe based on the amino terminal sequence of p-36 was used to
      identify a clone from a human spleen cDNA library. The cDNA insert was subcloned
      into the EcoR1 site of pUC-19, and both strands were sequenced. Southern blot
      analysis was used to study the genomic hybridization pattern. p-36 cDNA was
      subcloned in a pSG5 expression vector, and the construct was used to transfect
      COS-7 cells. RESULTS: The cDNA sequence contained an open reading frame of 966
      base pairs encoding a protein of 322 amino acids, an untranslated region of 322
      base pairs, and 2693 base pairs at the 5' and 3' ends, respectively. The deduced
      amino acid sequence showed 96.8% identity with the carboxy-terminal region of a
      yeast nucleopore complex protein, nup 100. Southern blot analysis of human
      genomic DNA revealed a simple hybridization pattern. Transfection of p-36 cDNA in
      COS-7 cells resulted in the presence of p-36 mRNA and expression of protein.
      CONCLUSIONS: The 36 kDa protein (p-36) detected at increased levels in the blood
      of patients with active pars planitis was cloned from a human spleen cDNA
      library. Its deduced amino acid sequence is homologous with the carboxy-terminal
      region of a nucleopore complex protein. Thus, we refer to this protein as nup36.

PMID- 8759359
TI  - Local carboplatin therapy in transgenic murine retinoblastoma.
AB  - PURPOSE: To determine the efficacy and toxicity associated with intraocular
      delivery of carboplatin in the treatment of murine transgenic hereditary
      retinoblastoma. METHODS: Forty-eight transgenic BLH-SV40 Tag retinoblastoma mice
      were administered five intravitreal injections of carboplatin in one eye. After
      12 weeks, the eyes were examined histopathologically to evaluate tumor burden.
      Twelve rabbits were administered intravitreal injections of carboplatin in one
      eye, after which they underwent serial electroretinography. All experimental and
      control eyes were obtained for histopathology and electron microscopy. RESULTS: A
      dose-dependent inhibition of intraocular tumor growth by carboplatin was observed
      in transgenic retinoblastoma mice. Tumor development was inhibited in 50% of the
      mouse eyes at doses of 1.4 micrograms. In rabbits, retinal toxicity resulted when
      intravitreal injections of carboplatin were administered at doses of 10
      micrograms or higher. CONCLUSIONS: Local delivery of carboplatin in serial doses
      effectively inhibits intraocular tumor growth in a dose-dependent manner in
      transgenic murine retinoblastoma.

PMID- 8759360
TI  - Platelet activating factor inhibits fluid transport by corneal endothelium.
AB  - PURPOSE: Given reports of corneal edema after endothelial exposure to platelet
      activating factor (PAF), the authors have investigated whether PAF can affect the
      function of corneal endothelium in vitro. METHODS: The endothelial side of
      deepithelialized rabbit corneas was perfused with BSS+ and test agents: PAF, its
      inactive receptor ligand analog Lyso-PAF, and its antagonist BN52021. Stromal
      thickness was determined by specular microscopy. Translayer-specific electrical
      resistance (rho) was measured in cultured bovine corneal endothelial cells grown
      on permeable substrates at 36.5 degrees C. RESULTS: Control corneas perfused with
      BSS+ or with BSS+ containing Lyso-PAF swelled at a very slow rate (6.2 +/- 0.1,
      and 7.9 +/- 0.2 microns/hour, respectively). Corneas exposed to PAF swelled
      appreciably faster and at rates that were a saturable function of PAF (K(m), 2.1
      microM); maximal rates of swelling were < 20 microns/hour, indicating no
      appreciable damage to intercellular junctions. BN52021 prevented PAF-induced
      swelling (Ki, 1.1 microM). PAF led also to a decrease in rho (from 42.8 +/- 1.4
      to 24.5 +/- 0.6 omega cm2 in 1 hour; 46.8 +/- 1.5 to 38.3 +/- 1.4 omega cm2 in
      control layers; and 43.0 +/- 1.2 to 30.8 +/- 1.6 omega cm2 in layers exposed to
      PAF+BN52021). Such rho changes are consistent with swelling of intercellular
      spaces. CONCLUSIONS: Results suggest that PAF inhibits transendothelial fluid
      transport on binding to an endothelial cell receptor for it; continuous
      stimulation of a PAF-induced signaling cascade may lead to such inhibition. From
      these and other results, fluid transport might result from cascades activating
      sequentially basolateral and apical transporters or channels.

PMID- 8759361
TI  - Molecular cloning of a rhodopsin gene from salamander rods.
AB  - PURPOSE: Salamander photoreceptor cells have been used widely as models in vision
      research. However, the salamander opsin genes had not been cloned. The purpose of
      this study was to clone a salamander rhodopsin and to determine its primary
      structure and cell type-specific expression. METHODS: Using salamander retina RNA
      as a template and Xenopus rhodopsin-specific oligonucleotides as primers, reverse
      transcription and polymerase chain reaction (RT-PCR) were used to amplify and
      clone a rhodopsin cDNA fragment. This fragment was used as a probe to isolate a
      full-length cDNA of the rhodopsin from a cDNA library of salamander retina. The
      dideoxynucleotide chain termination method was used to determine the nucleotide
      sequence. Single rod and cone cells were isolated by micromanipulation, and the
      absorbance spectra of the rod outer segments were measured with a photon-counting
      microspectrophotometer. Individual rod and cone cells were lysed for RT-PCR and
      Southern blot analysis to detect cell-specific expression of this gene. RESULTS:
      A 1.2 kb rhodopsin cDNA containing the full-length coding region of rhodopsin has
      been cloned and sequenced from the larval tiger salamander, Ambystoma tigrinum.
      This cDNA encodes 354 amino acids that, by hydropathy profile, could form seven
      transmembrane domains characteristic of other rhodopsins. Sequence identity was
      found with other amphibian rhodopsins at the nucleic acid (82% to 83%) and the
      amino acid (88% to 89%) levels. Key amino acids critical for structure and
      function of rhodopsin have been retained. The mRNA of this rhodopsin was
      identified in red rod cells (lambda max 506 nm). No expression of the gene was
      detected in cone cells. CONCLUSIONS: The cloned rhodopsin is a newly isolated
      member of the G protein-coupled receptor superfamily. This protein is expressed
      in rods but not in cones.

PMID- 8759362
TI  - Gene transfer with liposomes to the intraocular tissues by different routes of
      administration.
AB  - PURPOSE: To determine whether a reporter gene carried by liposomes can be
      introduced into the ocular tissues in vivo by different routes of administration.
      METHODS: Three different kinds of liposomes carrying plasmid DNA with beta
      galactosidase gene were applied topically to the eye or were injected into the
      anterior chamber, subretinal space, and vitreous of adult Wistar rats. Gene
      expression was detected by enzymatic color reaction using X-gal as a substrate in
      enucleated eyes 1 day, 1 week, and 1 month after topical application or
      injection. RESULTS: Topical application could transfer the gene to retinal
      ganglion cells. Injection into the anterior chamber delivered the gene to the
      basal layer of the corneal epithelium, ciliary epithelium, stroma of the ciliary
      body and iris, and retinal ganglion cells. Injection into the vitreous or
      subretinal space resulted in the expression of the gene in the ciliary
      epithelium, stroma of the ciliary body and iris, retinal ganglion cells, and
      retinal pigment epithelial cells. CONCLUSIONS: Efficient and stable transfer of
      the functional gene could be achieved by liposomes in the cornea, iris, ciliary
      body, and retina of rats. Liposomes appear to be a promising vehicle for
      delivering therapeutic genes in vivo to mammalian intraocular tissues.

PMID- 8759363
TI  - Localization of TIMP-3 mRNA expression to the retinal pigment epithelium.
AB  - PURPOSE: To evaluate ocular sites of expression of the tissue inhibitor of
      metalloproteinases-3 gene (TIMP-3). METHODS: In situ hybridization was performed
      on frozen sections of albino mouse eyes using riboprobes generated to the 3'
      untranslated region of TIMP-3. RESULTS: TIMP-3 mRNA expression was detected
      strongly in the retinal pigment epithelium (RPE) and to a minor extent in the
      ciliary epithelium, but not at any other site within the eye. CONCLUSIONS:
      Expression of TIMP-3 in the RPE is consistent with the recent demonstration of
      TIMP-3 mutations in patients with Sorsby's fundus dystrophy, a condition marked
      by the early onset of choroidal neovascularization in the macula. Unlike many of
      the recently described genes that cause human retinal disease, TIMP-3 is
      preferentially expressed in the RPE of the normal eye, as opposed to the
      photoreceptors.

PMID- 8759364
TI  - Effect of tumor necrosis factor alpha on rabbit corneal endothelial permeability.
AB  - PURPOSE: Tumor necrosis factor alpha (TNF alpha) is present in the iris and the
      lacrimal gland, and its concentration is increased during inflammation and after
      corneal wounding. Although TNF alpha has been shown to increase keratocyte and
      corneal epithelial interleukin production, no definitive effects of TNF alpha on
      corneal endothelial cells have been reported. TNF alpha has been shown to disrupt
      barrier function in vascular endothelial monolayers through f-actin
      depolymerization. A reduction in intracellular cyclic adenosine monophosphate
      (cAMP) concentration may play a role in this response. This study was designed to
      examine the role and signal transduction mechanisms of TNF alpha modulation of
      endothelial permeability in the cornea. In addition, it is the first examination
      of the effects of TNF alpha on the barrier function of a noncultured cell
      monolayer. METHODS: Rabbit corneal endothelial superfusions were performed under
      an in vitro specular microscope. Corneas were processed for permeability
      measurements or f-actin staining. RESULTS: TNF alpha superfused corneas had
      significantly higher permeabilities than controls. f-actin staining revealed that
      TNF alpha superfusion disrupted f-actin filaments when compared to controls.
      Corneas superfused with the f-actin stabilizing agent phallacidin had
      significantly lower permeabilities than TNF alpha superfused pairs.
      Permeabilities of corneas superfused with TNF alpha plus 8-bromo-cAMP (0.01 to 3
      mM) were significantly lower than TNF alpha superfused pairs at all
      concentrations, although only significantly lower at the 0.1 mM cAMP
      concentration. CONCLUSIONS: TNF alpha causes an increase in corneal endothelial
      permeability, and this increase is mediated by disruption of f-actin filaments;
      cAMP appears to be involved in this response.

PMID- 8759365
TI  - Subfoveal fibrovascular membranes in age-related macular degeneration express
      vascular endothelial growth factor.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is a potent and specific
      angiogenic growth factor, in vitro and in vivo, that may be associated with the
      development of intraocular neovascularization. In the current study, the authors
      analyze the expression of VEGF in subfoveal fibrovascular membranes from patients
      with age-related macular degeneration. METHODS: Surgically removed subfoveal
      fibrovascular membranes from 18 eyes were analyzed for the expression of VEGF
      mRNA and protein using in situ hybridization and immunohistochemistry,
      respectively. RESULTS: Most specimens expressed both VEGF mRNA and protein. The
      VEGF mRNA expression was particularly high in areas with a marked inflammatory
      response, in which the expression was concentrated to cells resembling
      fibroblasts and to surrounding inflammatory cells. VEGF protein expression was
      seen in fibrovascular parts of the membranes and was predominantly localized to
      the cytoplasm of fibroblastlike cells. In some of these membranes, strong VEGF
      protein immunoreactivity also was concentrated to extracellular matrix foci
      within the fibrovascular stroma. CONCLUSIONS: Results indicate that VEGF may be
      of pathogenetic importance for the development of the choroidal
      neovascularization (age-related macular degeneration) and also may implicate a
      role of fibroblasts of presumable choroidal origin in this process.

PMID- 8759366
TI  - Atlantic salmon (Salmo salar) fed L-carnitine exhibit altered intermediary
      metabolism and reduced tissue lipid, but no change in growth rate.
AB  - Metabolic evidence was sought to explain the reduced body fat and increased body
      protein observed in Atlantic salmon fed diets supplemented with L-carnitine. By
      stimulating fatty acid oxidation, dietary carnitine might increase flux through
      pyruvate carboxylase and decrease flux through the branched-chain alpha-keto acid
      dehydrogenase complex, by increasing regulatory ratios of acetyl CoA:free enzyme
      A (CoA-SH) and ATP:ADP. Such changes could conserve nitrogen by providing more
      carbon for amino acid biosynthesis and by blocking oxidative loss of the branched
      chain amino acids. Consistent with this hypothesis, salmon fed carnitine (23
      mmol/kg diet) for 9 wk exhibited greater metabolic rates than cohorts fed a
      carnitine-free diet (P < 0.05) for the following: 1) 1-[14C] palmitate oxidation
      by liver cubes (48%) and by isolated hepatocytes (151%), 2) pyruvate-dependent
      [14 CO2]-fixation by isolated mitochondria (81%), 3) incorporation of 1-[14C]
      lactate into glucose by liver cubes (120%) and by isolated hepatocytes (210%),
      and 4) incorporation of [35S]-methionine into the acid-insoluble fraction of
      liver cubes (59%) and isolated hepatocytes (89%). Hepatic concentrations of seven
      amino acids, including the branched-chain amino acids, were greater (7-112%), as
      were the plasma concentrations of three of these (45-130%). However, 230% more
      enzyme in the mitochondria of carnitine-fed fish, and not a difference in the
      ratios of acetyl CoA:CoA-SH or ATP:ADP, appeared to account for accelerated flux
      through pyruvate carboxylase; flux through the dehydrogenase complex was
      unchanged. These results implicate induction of pyruvate carboxylase (or a
      reduction in turnover) and enhanced protein synthesis in the mechanism for
      carnitine-induced changes in gluconeogenesis and nitrogen metabolism.

PMID- 8759367
TI  - Dietary (n-3) polyunsaturated fatty acids improve adipocyte insulin action and
      glucose metabolism in insulin-resistant rats: relation to membrane fatty acids.
AB  - To study the effects of dietary fish oil on insulin-stimulated glucose metabolism
      in adipocytes of insulin-resistant rats (rats fed 50% sucrose and 30% fat),
      eighteen 5-wk-old Sprague-Dawley rats were fed, for 6 wk, a diet containing 30%
      fat as either fish oil (FO) or a mixture of vegetable and animal oils [control
      oils (CO)]. A third reference group was fed a standard diet (62% corn starch and
      13% fat). At the end of the 6-wk period, the two experimental groups had
      comparable plasma glucose concentrations that were higher than that found in the
      reference group. FO feeding corrected the hyperinsulinemia of the experimental
      rats (P < 0.05) to reach values in the reference group. Plasma triacylglycerol (P
      < 0.01) and cholesterol (P < 0.001) concentrations were also lower in rats fed FO
      than in those fed CO. The body weights of FO-fed rats were similar to that of CO
      fed rats, but epididymal adipose tissue weight was lower (P < 0.01). Adipocytes
      of FO-fed rats, compared with those of CO-fed rats, had high insulin-stimulated
      glucose transport (P < 0.05), oxidation (P < 0.001) and incorporation into total
      lipids (P < 0.05). The incorporation of (n-3) polyunsaturated fatty acids in
      adipocyte membrane phospholipids was higher in FO-fed rats than in those fed CO
      (P < 0.0001). Insulin action was positively correlated with the fatty acid
      unsaturation index in membrane phospholipids. Thus dietary fish oil has
      beneficial effects on insulinemia, plasma lipids and insulin-stimulated glucose
      metabolism in insulin-resistant slightly diabetic rats.

PMID- 8759368
TI  - Exercise down-regulates hepatic lipogenic enzymes in food-deprived and refed
      rats.
AB  - The effects of an acute bout of prolonged exercise on the activities of several
      hepatic lipogenic enzymes and the abundance of fatty acid synthase (FAS) mRNA
      were evaluated using a food deprivation-refeeding protocol in which diets
      contained 50% of the energy from either fructose or cornstarch. Food was withheld
      from male rats for 48 h and refed for 0, 4, 8, 12, 24 or 48 h. At each time
      point, half of each dietary group was subjected to a single bout of treadmill
      running until exhaustion and killed immediately. The other half of each group
      rested without food for the same amount of time before being killed. Exercise
      significantly decreased FAS activity by 57, 46, 10, 26 and 70% at 4, 8, 12, 24
      and 48 h of refeeding, respectively, in the fructose-fed rats; and by 70 and 63%
      at 24 and 48 h of refeeding, respectively, in the cornstarch-fed rats. Activities
      of L-type pyruvate kinase and glucose 6-phosphate dehydrogenase were
      significantly decreased after exercise in the fructose-fed, but not cornstarch
      fed rats. In rested rats, FAS mRNA abundance increased approximately fourfold
      above the unfed levels after 8 and 12 h of refeeding. Exercise attenuated the
      diet-induced increases in FAS mRNA abundance. At 8 h of refeeding, both
      cornstarch- and fructose-fed exercised rats had 71% (P < 0.05) of the FAS mRNA
      levels of their rested counterparts; at 12 h, these exercised rats showed only 46
      and 27% (P < 0.05) of FAS mRNA levels compared with rested rats fed the same
      diet. We conclude that dietary induction of FAS activity and mRNA abundance can
      be inhibited by prolonged exercise, suggesting that exercise may influence FAS
      transcription and/or mRNA stability.

PMID- 8759369
TI  - Amaranth and its oil inhibit cholesterol biosynthesis in 6-week-old female
      chickens.
AB  - All amaranth varieties contain tocotrienols and squalene compounds which are
      known to affect cholesterol biosynthesis. Therefore, in the present study, the
      influence of dietary supplementation of whole seed, popped, and milled amaranth
      and amaranth oil on cholesterogenesis was studied in 6-wk-old female chickens.
      Serum total cholesterol and LDL-cholesterol were lowered 10-30% and 7-70% (P <
      0.01), respectively, in birds fed amaranth-containing diets. HDL-cholesterol was
      not affected by amaranth supplementation. Activities of liver cholesterol 7alpha
      hydroxylase (the enzyme responsible for cholesterol breakdown into bile acids)
      were 10-18% higher (P < 0.01) than those of controls for birds fed most forms of
      amaranth and its oil, whereas activities of liver 3-hydroxy-3-methylglutaryl
      coenzyme A reductase (the rate-limiting enzyme for cholesterol biosynthesis) were
      lowered by about only 9% (P < 0.01) by popped, milled amaranth and its oil. This
      lack of marked inhibition of this enzyme suggests the presence of some other
      potent cholesterol inhibitor(s) apart from tocotrienols and squalene in amaranth.

PMID- 8759370
TI  - Dietary guar gum alters colonic microbial fermentation in azoxymethane-treated
      rats.
AB  - To assess the effects of guar gum on colonic microbial fermentation and cancer
      development, azoxymethane-treated rats were fed a partially hydrolyzed guar or
      control diet. Anaerobic fecal incubations were conducted at 8-wk intervals,
      either without added substrate or with cornstarch or hydrolyzed guar as
      substrates. Short-chain fatty acids in colonic contents and colonic carcinoma
      areas were measured at 27 wk. Fecal in vitro fermentation rates were higher for
      guar-fed rats than for control rats [three-way ANOVA (diet, time, in vitro
      substrates), P = 0.002]. Fecal in vitro butyrate production was greater for guar
      fed rats than for control rats after 3-11 weeks of diet treatment (three-way
      ANOVA, P = 0.027). Butyrate concentrations of colonic contents at 27 wk were
      higher in guar-fed than in control rats and higher in the cecum than in the post
      cecal colon (two-way ANOVA, P = 0.0001). A regression equation predicting colonic
      carcinoma area (r2 = 0.279) using propionate and butyrate concentrations of the
      contents of the post-cecal colon showed propionate as a positive predictor (P <
      0.001) and butyrate as a negative predictor (P = 0.033). Our results show that
      patterns of short-chain fatty acid production may affect the results of fiber
      carcinogenesis experiments. Dietary addition of hydrolyzed guar is associated
      with fecal fermentation low in propionate and high in butyrate; short-chain fatty
      acid concentrations are greater proximally than distally. These results suggest
      that butyrate protects against colonic neoplasia, whereas propionate enhances it,
      and demonstrate that colonic microbiota adapt to produce more butyrate if given
      time and the proper substrate.

PMID- 8759371
TI  - Functional and psychic deterioration in elderly people may be aggravated by
      folate deficiency.
AB  - The deterioration of functional and mental capacity is one of the major problems
      of the elderly. This deterioration may be caused or worsened by folate
      deficiency. The aim of this investigation was to analyze the relationship between
      mental and functional capacities and folate status in a group of 177 elderly
      Spanish people. Folate deficiency is common in the Spanish population. In this
      study, 48.6% of the elderly subjects had folate intakes below recommended values
      (200 microg/day), 34.9% had serum concentrations < 14 nmol/L and 6.6% had <360
      nmol/L erythrocyte folate. Subjects took part in a series of tests: Katz' scale
      of activities of daily living, Lawton's scale of instrumental activities of daily
      living, Pfeiffer's mental status questionnaire, Folstein's Mini-Mental State Test
      and the Geriatric Depression scale of Yesavage. The results for Lawton's scale of
      instrumental activities of daily living were significantly better (indicating
      greater independence and capacity) when folate intake and serum or erythrocyte
      folate concentrations were adequate (i.e., folate intake no less than
      recommended, > or = 14 nmol/L serum folate or > or = 360 nmol/L erythrocyte
      folate). Subjects with adequate Mini-Mental State Exam results (> or = 28 points)
      had serum and erythrocyte folate concentrations significantly higher than those
      with less adequate results (<28 points). Thus, there is evidence to suggest that
      the folate status of the elderly should be monitored and, if possible, improved.

PMID- 8759372
TI  - A soy protein isolate rich in genistein and daidzein and its effects on plasma
      isoflavone concentrations, platelet aggregation, blood lipids and fatty acid
      composition of plasma phospholipid in normal men.
AB  - The effects of consuming a soy protein isolate beverage powder (60 g/d for 28 d)
      vs. a casein supplement was evaluated in 20 male subjects who were randomly
      allocated into the two groups. A dramatic rise in plasma isoflavone
      concentrations was observed after supplementation in the soy protein group, the
      levels reaching 907 +/- 245 nmol/L for genistein (a 110-fold increase) and 498 +/
      102 nmol/L for daidzein (a 150-fold increase) as measured by isotope dilution
      gas chromatography - mass spectrometry. These concentrations are higher than
      previously reported for the plasma of Japanese subjects consuming a traditional
      diet (276 nmol/L and 107 nmol/L, respectively). No significant differences in
      collagen- or 9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin F2alpha
      (U46619)-induced platelet aggregation were observed in platelet-rich plasma from
      the two groups; the increase in plasma isoflavonoids from soy protein
      supplementation is not sufficient to significantly inhibit platelet aggregation
      ex vivo. Similarly, plasma total and HDL-cholesterol were not affected by protein
      supplementation, possibly because the men were normocholesterolemic at entry.
      Analysis of plasma phospholipid polyunsaturated fatty acid composition showed no
      differences between soy protein and casein supplementation. Previous
      investigations reported a significant alteration in fatty acid status in animals
      fed soy protein relative to those fed casein. The present studies indicate that
      although soy protein supplementation to a typical Western diet can increase
      plasma concentrations of isoflavones, this may not necessarily be sufficient to
      counter heart disease risk factors such as high plasma cholesterol and platelet
      aggregation.

PMID- 8759373
TI  - Soy protein concentrate and isolated soy protein similarly lower blood serum
      cholesterol but differently affect thyroid hormones in hamsters.
AB  - There is a wide variation in the hypocholesterolemic response to ingestion of soy
      protein in humans. One possible explanation is that the different soy protein
      preparations used contain different spectra of biologically active components.
      This could affect a number of indices including thyroid hormone status. An
      increased level of thyroxine has been proposed as an underlying mechanism of the
      hypocholesterolemic effect of soy protein. The objective of this study was to
      determine if serum cholesterol and thyroid hormone concentrations differed
      because of feeding soy protein from different sources. Twenty-nine male weanling
      golden Syrian hamsters were fed rations containing 25 g/100 g protein from either
      isolated soy protein (ISP), soy protein concentrate (SPC) or casein for 35 d.
      Serum total cholesterol concentrations were lower in hamsters fed ISP and SPC
      compared with those fed casein (P < 0.05). No differences in cholesterol
      concentrations were observed in lipoprotein fractions. Serum thyroxine and free
      thyroxine were greater only in hamsters fed ISP than in those fed casein (P <
      0.05), whereas triiodothyronine concentrations were higher in casein-fed than in
      SPC-fed hamsters (P < 0.05). Results indicate that protein from ISP and SPC are
      both effective in lowering blood cholesterol concentrations, whereas only ISP
      increases thyroxine concentrations. Therefore, it appears unlikely that
      modulation of thyroid hormone status is responsible for the cholesterol-lowering
      effect of soy protein.

PMID- 8759374
TI  - Dose-dependent production of mammalian lignans in rats and in vitro from the
      purified precursor secoisolariciresinol diglycoside in flaxseed.
AB  - The mammalian lignans enterodiol (ED) and enterolactone (EL) produced from
      colonic bacterial action on dietary precursors have exhibited anticarcinogenic
      effects in vitro. The major lignan precursor in flaxseed (a rich source) has been
      identified as secoisolariciresinol diglycoside (SDG). The purpose of this study
      was to first isolate SDG and determine whether 1) SDG accounted for all the
      lignan production from flaxseed; 2) this production was dose-related; and 3) a
      relationship between in vitro production and in vivo urinary excretion existed.
      Extraction of flaxseed with dioxane:ethanol (1:1, v/v) followed by
      chromatographic separations yielded the purified SDG. Rats were fed a high fat
      diet without/with 2.5, 5 or 10 g/100g ground flaxseed or 1.1, 2.2 or 4.4 micromol
      SDG/d (equivalent to levels in the respective flaxseed diets) for 4 wk. In vitro
      lignan production was assessed by fermenting flaxseed or SDG for 24 h with human
      fecal inoculum. Urinary lignan excretion increased linearly with doses from 0-5%
      flaxseed and 0-2.2 micromol SDG/d followed by a plateau, indicating a threshold
      response. When all doses were considered, a curvilinear relationship was
      observed. A similar trend was seen in vitro for SDG, resulting in a high
      correlation between in vitro production and in vivo excretion of lignans (r =
      0.990, P < 0.02). Thus in vivo response can be predicted with confidence based on
      in vitro results. Theoretical urinary ED + EL from the SDG present in flaxseed
      correlated with the actual excretion in flaxseed-fed animals (r = 0.655, P <
      0.005). However, urinary ED + EL of SDG-fed rats was only 20% of levels of
      flaxseed-fed rats, indicating the presence of other precursors or incomplete
      conversion of SDG to ED and EL.

PMID- 8759375
TI  - Food deprivation modifies fatty acid partitioning and beta-oxidation capacity in
      rat liver.
AB  - The involvement of lipids under starvation conditions in the shift from the phase
      of protein sparing (phase II) to the phase of increased protein breakdown (phase
      III) has been investigated. Plasma and liver were sampled from fed and unfed rats
      at two distinct stages which were characterized according to the changes in
      specific loss in daily body mass and nitrogen excretion. In the two groups of
      food-deprived rats corresponding to phases II and III, the liver concentration of
      triglycerides (micromol/g) was significantly lower, that of cholesterol
      significantly higher and that of the other lipid classes was moderately affected
      compared with concentrations in fed rats. Hepatic phospholipids had significantly
      higher concentrations (mol/100 mol) of 22:6(n-3) in food-deprived rats than in
      fed rats. Triglycerides had significantly higher concentrations of stearic and
      arachidonic acids in livers of both groups of food-deprived rats compared with
      fed rats. The total activity of carnitine palmitoyl transferase [mmol/(min x
      liver)] was 48% higher in rats studied at the end of phase II than in fed rats
      but was similar in fed rats and in rats studied at the beginning of phase III.
      The total activity of fatty acyl-CoA oxidase was 73% lower only in rats studied
      at the beginning of phase III when compared with fed rats. Our results indicate
      that during food deprivation the change in the rate of protein utilization is
      associated with important qualitative and quantitative alterations of hepatic
      lipids and oxidative capacity of fatty acids. These modifications appear to be
      related to the change from a preferential use of lipids to a preferential
      utilization of proteins.

PMID- 8759376
TI  - Reduced digestibility of beef tallow and cocoa butter affects bile acid excretion
      and reduces hepatic esterified cholesterol in rats.
AB  - We investigated stearic acid (18:0) digestibility and how it affects bile acid
      excretion in male Sprague-Dawley rats fed diets containing (g 18:0/ 100 g fatty
      acids): pork lard (13); beef tallow (19); cocoa butter (35); corn oil (2) or corn
      oil plus cholestyramine for 25 d. Apparent lipid digestibility was reduced with
      increased dietary intake of 18:0 as follows: lard (90%), beef tallow (82%), cocoa
      butter (78%), cholestyramine (87%), and corn oil (94%); P < 0.001, pooled SD = 2.
      Hepatic concentrations of total and esterified cholesterol were significantly
      less in cocoa butter-, beef tallow- and cholestyramine-fed groups compared with
      lard- and corn oil-fed groups. Fecal bile acid excretion was significantly
      greater in rats fed cocoa butter or cholestyramine compared with those fed corn
      oil. The half-life of intraperitoneally administered 14C-cholic acid was
      significantly longer in rats fed cocoa butter (1.36 +/- 0.02 d) compared with
      cholestyramine (0.98 +/- 0.03 d) and intermediate in those fed corn oil, lard or
      beef tallow (1.11-1.21 +/- 0.05 d). Fecal excretion of muricholic acids (bile
      acids) correlated strongly with dietary intake of 18:0 (r2 = 0.98, P < 0.01),
      whereas excretion of bile acids derived from cholic and chenodeoxycholic acids
      was similar among groups. In summary, the lower digestibility of cocoa butter is
      associated with increased fecal bile acid excretion, reduced hepatic
      concentration of esterified cholesterol, decreased fractional turnover of 14C
      cholic acid and increased excretion of muricholic acids in rats. The mechanism by
      which stearate-rich dietary fats alter bile acid and cholesterol metabolism is,
      however, uncertain.

PMID- 8759377
TI  - Energy metabolism and protein balance in growing rats housed in 18 degree C or 28
      degree C environments and fed different levels of dietary protein.
AB  - A study was performed to investigate the effect of environmental temperature and
      increasing levels of protein in the diet on visceral organ size, digestibility,
      protein balance and energy metabolism in rats. Thirty-six male Wistar rats,
      initial body weight 77-80 g, were used in a factorial design consisting of three
      levels of dietary protein and two environmental temperatures of either 18 or 28
      degrees C. Three fish meal-based diets were prepared to contain 91, 171 and 262 g
      protein (N X 6.25/kg diet). Gas-exchange measurements were made and urine and
      feces were quantitatively collected. The weights of the visceral organs from rats
      housed at 18 degrees C were greater (P < 0.05) than those of rats housed at 28
      degrees C. The digestibilities of dry matter and protein were not affected by
      environmental temperature, whereas fat and energy digestibilities were higher (P
      < 0.05) at 18 degrees C than at 28 degrees C. As the level of protein was
      increased, the digestibilities of protein, energy and fat increased (P < 0.05).
      Protein intake and protein retention were higher at 18 degrees C (P < 0.05) than
      at 28 degrees C and increased (P < 0.05) as dietary protein concentration
      increased. Apparent biological value was lower (P < 0.05) at 18 degrees C than at
      28 degrees C and decreased (P < 0.05) as dietary protein level increased. Heat
      production as a percentage of metabolizable energy was higher (P < 0.05) for the
      low protein diet than for the medium and high protein diets. The efficiency of
      energy utilization was depressed (P < 0.05) for the high protein diet when rats
      were kept at 28 degrees C. The results suggest that thermogenesis was induced
      when low protein was fed. The increase in thermogenesis may have been important
      in regulating energy balance and maintaining a constant body temperature in a
      cold environment.

PMID- 8759378
TI  - Long-term low ascorbic acid intake reduces bone mass in guinea pigs.
AB  - The effect of long-term (1 y) low to excess ascorbic acid (AA) intake on bone
      mass was evaluated using guinea pigs that were 12-14 d old at the start of the
      experiment. Dietary AA was low (0.15 g/ kg diet) (n = 7), normal (0.50 g/kg) (n =
      8) or excess (10 g/kg) (n = 8). After 12 mo, total body bone mineral density
      (BMD, mg/cm2) and bone mineral content (BMC, g) were determined by dual energy X
      ray absorptiometry. Histomorphometric analysis of the cancellous bone of the
      proximal tibial metaphysis was completed after in vivo dual fluorochrome
      labeling. Total body BMD of the low AA group was 4.9% lower (P < 0.05), and total
      body BMC was 12.4% lower (P < 0.05) than in the normal AA group. Total body BMD
      and BMC were similar in normal and excess AA groups and in the low and excess AA
      groups. Histomorphometric analysis indicated significantly greater (P < 0.05)
      double-labeled bone surface, mineralizing surface, and bone formation rate in the
      low AA guinea pigs compared with the normal AA animals. Thus, there was greater
      bone turnover in the low AA group than in the normal AA guinea pigs. No
      differences in histomorphometric endpoints existed between the normal AA and
      excess AA groups. Long-term AA deficiency, during the period of rapid growth and
      slower phases of skeletal maturation, resulted in bone abnormalities in adult
      guinea pig skeletons. Long-term dietary AA excess caused no such abnormalities.

PMID- 8759379
TI  - Hepatic betaine-homocysteine methyltransferase activity in the chicken is
      influenced by dietary intake of sulfur amino acids, choline and betaine.
AB  - There is much interest in the metabolism of homocysteine, because elevated plasma
      homocysteine [hyperhomocyst(e)inemia] is an independent risk factor for the
      development of cardiovascular disease. Four chick assays were conducted to
      determine the effects of varying dietary sulfur amino acids, choline and betaine
      on the activity of hepatic betaine-homocysteine methyltransferase (BHMT), an
      enzyme likely to be important in modulating plasma homocysteine. In Experiment 1,
      chicks were fed a purified crystalline amino acid diet containing adequate sulfur
      amino acids and choline. Excess dietary methionine, or the combination of excess
      cystine with choline or betaine, caused a small increase (P < 0.05) in BHMT
      activity. In Experiment 2, use of a methionine-deficient purified diet resulted
      in a threefold increase (P < 0.05) in BHMT activity, and addition of choline or
      betaine further increased (P < 0.05) BHMT activity. In Experiment 3, use of a
      methionine-deficient corn-peanut meal diet increased BHMT (P < 0.05) relative to
      that of chicks supplemented with adequate methionine, and addition of surfeit
      choline to the methionine-deficient basal diet caused a further increase (P <
      0.05). In Experiment 4, addition of both surfeit choline and surfeit betaine to
      the methionine-deficient corn-peanut meal diet caused an increase (P < 0.05) in
      BHMT activity relative to that observed in chicks fed the methionine-deficient
      basal diet. These assays show that large increases in BHMT activity can be
      produced under methionine-deficient conditions, especially in the presence of
      excess choline or betaine.

PMID- 8759380
TI  - [Adrenaline in anaphylaxis].

PMID- 8759381
TI  - [Obesity. New therapeutic perspectives].

PMID- 8759382
TI  - [Self-administration of adrenaline aerosol in anaphylactic reactions after insect
      stings].
AB  - A serious allergic reaction after an insect sting is wellknown source for concern
      and anxiety. Patients with known hypersensitivity to insect stings are usually
      equipped with an adrenaline self-injection kit by an allergologist. In Denmark a
      new device for self-medication of adrenaline was approved in 1994, the adrenaline
      aerosol spray, Adrenalin Medihaler. The article is based on former studies and
      experiences, related to the usage of an adrenaline aerosol spray for the
      treatment of anaphylactic reactions after an insect sting. We conclude that
      adrenaline aerosol treatment should play an important role as emergency treatment
      for anaphylactic reactions after insect stings, and in most cases can replace the
      use of adrenalin self-injection kits. Adrenaline aerosol self-treatment could
      have an important beneficial effect helping to avoid exacerbation of the initial
      symptoms after insect venom exposition, such as bronchial obstruction and
      laryngeal oedema.

PMID- 8759383
TI  - [Etiology of endometrial cancer].
AB  - Based on a survey of the literature, a summary of the etiology of endometrial
      cancer (EC) is presented. The effect of a number of expositions on the risk of
      developing EC, expressed as odds ratio or relative risk, are indicated. Combining
      these with the prevalence of the specific exposition allows calculation of the
      etiologic fraction (EF) for each risk factor. The etiologic fraction indicates
      the proportion of EC that would disappear if the exposition were eliminated.
      Obesity increases the risk of EC with a factor three to four. One quarter of
      Danish women of 60-70 years of age have a relative weight exceeding 1.2 times the
      ideal weight. The corresponding EF is 41%. Oestrogen substitution therapy is
      connected with an odds ratio of EC of 3.8 and an EF of 8%, anticipating that the
      lifetime prevalence of pure oestrogen substitution is 3%. On the other hand, oral
      contraceptives imply a reduction in EC of 14%, parity of 37% and cigarette
      smoking of 26%. It appears that the etiology of EC is multifactorial, and that a
      number of disposing and protecting factors are identified and quantified. The
      greatest prophylactic potential seems to be in reducing weight among obese women.

PMID- 8759384
TI  - [Leptin--a new way to diet?].
AB  - The relatively constant level of body fat in the adult mammal is explained by the
      lipostat theory as follows: A factor is released from adipose tissue in amounts
      that reflect total body fat content. This factor is then registered by the
      hypothalamic centres that regulate appetite. The theory has gained particular
      support from parabiotic experiments in genetically fat mice, amongst whom the so
      called ob/ob mice appear to produce too little of the factor, whilst signal
      transduction to the satiety centre appears to be defective in the so-called db/db
      mice. The two genetic defects have recently been clarified, and it has been shown
      that the normal ob gene nodes for a protein called leptin. Leptin is released
      from adipose tissue, and its plasma concentration reflects total body fat. The
      normal db-gene codes for a hypothalamic receptor for leptin. These crucial
      discoveries have greatly supported the correctness of the lipostat theory. At
      present, extensive investigations of the roles of leptin and the leptin receptor
      in human adiposity are in progress.

PMID- 8759385
TI  - [Treatment of obesity in patient groups].
AB  - The purpose of this study was to assess the results of group treatment in
      obesity. Patients referred to a department of endocrinology were on referral
      given individual diet counselling, and the patients were then seen every second
      week for control weighing and supplemental counselling either in groups of 10-12,
      or individually. One hundred and twenty-three (97 female and 26 male) patients
      who during a two year period, 1991-1993, were referred to the outpatient clinic
      of the Department of Endocrinology were identified. Ninety-five percent of the
      patients were markedly obese, body mass index > 30 m2/kg. Seventy percent of the
      patients continued the treatment and were either followed in the groups or
      individually. The patients followed in the groups (n = 66) lost 5.2 kg during 127
      days (median), and this is not significantly different from those followed
      individually (n = 22) who lost 4.9 kg during 98 days. In conclusion, only a small
      weight reduction is seen in obese patients treated either in groups or
      individually. These results are comparable with previously reported results from
      a Danish study only using individual counselling.

PMID- 8759386
TI  - [Prognostic markers for weight loss in the treatment of obesity].
AB  - The aim of the study was to identify prognostic metabolic markers for long-term
      weight loss outcome in obese women. Forty female obese patients underwent a
      dietary intervention of 36 weeks treatment with a 4.2 MJ/d low-fat high
      carbohydrate diet and were followed-up two and a half years after cessation of
      treatment. The maximum weight loss (mean 16.2 kg. 95% CI 14.2-18.2) was
      positively associated to pre-treatment 24-h energy expenditure (EE) (p < 0.01),
      fat oxidation (%) (p < 0.02), plasma dihydrotestosterone (DHT) (p < 0.01), and to
      postprandial noradrenaline concentration (p < 0.04). Together these factors could
      explain 41% of the variation in maximum weight loss. After 36 weeks only 24-h EE
      and DHT had predictive power on weight loss. Weight losses in upper and lower
      tertiles of DHT concentrations were 17.7 kg (14.1-21.4) and 9.8 kg (6.2-13.3) (p
      < 0.02) and the adjusted relative risk of losing < 10 kg in the upper compared to
      the lower DHT tertile was 12% (4-32%). At two and a half years follow-up 21
      patients had maintained some of the weight loss (54%), while 14 patients had
      maintained > 5 kg weight loss (36%). High levels of pre-treatment DHT were also
      associated with better weight loss at two and a half years follow-up. The study
      suggests that long-term weight loss outcome may be predicted by pre-treatment
      metabolic and hormonal factors in obese women.

PMID- 8759387
TI  - [Small cell lung cancer].

PMID- 8759388
TI  - [Therapeutic results in localized ventricular non-Hodgkin's lymphomas. A
      retrospective study of 106 cases].
AB  - One hundred and six cases of localized gastric lymphomas reported to a population
      based register of non-Hodgkin lymphomas were analysed retrospectively to identify
      the optimum primary treatment. Five-year survival was 67%, and no type of
      treatment showed any superiority. Surgical resection was associated with
      significantly more unacceptable late complications than radiotherapy.
      Accordingly, the latter treatment should substitute surgery as the primary local
      treatment in localized gastric lymphoma.

PMID- 8759389
TI  - [Hemothorax and ectopic pregnancy].
AB  - Ectopic pregnancy presenting as haemothorax is extremely rare and difficult to
      handle. A case report concerning this problem is presented and a possible
      mechanism is discussed. The importance of bearing pregnancy in mind when fertile
      women present obscure symptoms is emphasized.

PMID- 8759390
TI  - [Formaldehyde in the occupational environment. A possible cause of chemically
      induced reactive arthritis].
AB  - A case is presented of a farmer aged 33 years who developed polyarthritis four to
      five days after having used formaldehyde for fumigation of his piggery. The
      farmer was admitted to the General Hospital in Herning for treatment. The course
      of the treatment was several months. Furthermore, two farm assistants and a
      bricklayer were exposed to formaldehyde in the piggery. They developed acute
      intoxication symptoms and, a few days after the exposure, arthralgia. There was
      no other collective exposure. Apart from the formaldehyde, there was a great
      amount of water in the piggery, leading to the conclusion that the exposure was
      due to the formaldehyde being absorbed in the water with following evaporation.
      In conclusion, a relationship between these particular circumstances of
      formaldehyde exposure and reactive arthritis is found to be likely.

PMID- 8759391
TI  - [Alternative fragments?].

PMID- 8759393
TI  - [A fat mutation].

PMID- 8759394
TI  - [Genetically reduced effect or deficiency of the hormone leptin as the cause of
      obesity].

PMID- 8759395
TI  - [Hypertensive crises].

PMID- 8759396
TI  - [Adrenaline for self treatment of anaphylactic reactions. Indications, available
      preparations and prescription rules].
AB  - Adrenaline is the drug of choice for the treatment of anaphylaxis. The
      indications, available formulations, and rules for prescribing adrenaline for
      self treatment of anaphylactic reactions in allergic subjects are summarized in
      this paper. Emergency kits containing adrenaline must be prescribed only to
      patients with a definite history of anaphylactic reactions or laryngeal oedema. A
      kit containing Adrenaline DAK 1 mg/ml in a traditional glass ampoule together
      with a 1 ml syringe and an i.m. cannula is the cheapest solution, and a usable
      alternative in the patient who after sufficient training feels safe to prepare
      his own injection. Ana-guard injector is recommended for the allergic adult due
      to its easy handling and the fact that it contains two doses of adrenaline 0.3
      mg. For both children and adults with a low bodyweight, the Epi-Pen automatic
      injector is recommended. It contains one dose of adrenaline (0.15 or 0.30 mg) and
      requires no preparation before use. The Adrenalin Medihaler is recommended for
      the treatment of laryngeal oedema and threatened airway obstruction. Due to the
      low and unpredictable absorption after inhalation, adrenaline injection is
      recommended for the treatment of systemic symptoms. Prescribing adrenaline in
      semi-or automatic injectors requires special permission from the Danish Health
      Authorities.

PMID- 8759397
TI  - [Symposium on Hyperandrogenemia. Zagreb, 22 March 1996. Croatian Medical
      Association, Subiceva 9, Zagreb].

PMID- 8759398
TI  - [Epidemiology, classification and clinical aspects of hyperandrogenemia].
AB  - Hyperandogenemia in women is manifested typically by clinical features that may
      include hirsutism, acne, central obesity, male pattern baldness, increased waist
      to-hip ratio, clitoral hypertrophy and deepening of the voice. The differential
      diagnosis include Cushing syndrome, PCO and iatrogenic hirsutism. Complications
      include cardiovascular disease, intravascular disease and insulin resistance. An
      interdisciplinary approach to management is strongly recommended. Risk reduction
      strategies include correction of dyslipidemias, low-dose aspirin for primary
      prevention of myocardial infarction, maintenance of ideal weight, smoking
      cessation, use of oral contraceptives with low progestin, and postmenopausal
      estrogen replacement.

PMID- 8759399
TI  - [Biosynthesis of steroids in the adrenal gland].
AB  - Cholesterol and steroid hormone biosynthesis, enzymes which catalyze each step in
      the biosynthesis, their localization and the genes that encode them are
      presented. The simplified mechanism of the enzyme cytochrome P450 action is
      described. It comprises alternative oxidation and reduction of flavoprotein
      adrenodoxin reductase, adrenodoxin and cytochrome P450. delta 4 and delta 5
      pathways for androgen biosynthesis and an alternative biosynthetic pathway for
      aldosterone and cortisol biosynthesis are also described.

PMID- 8759400
TI  - [Biosynthesis of steroids in the ovaries].
AB  - Biosyntheses of androgens and estrogens occur within the preovulatory follicle in
      the theca interna and granulosa cells, guided by gonadotropins, LH and FSH. The
      avascular granulosa cell layer is exposed to high concentrations of aromatizable
      androgen that reach it by diffusion from the theca interna. Estradiol is released
      into the bloodstream in greatest amounts as the follicle destined to ovulate
      completes its development in the late follicular phase.

PMID- 8759401
TI  - [Congenital adrenal hyperplasia due to 21-hydroxylase enzyme deficiency].
AB  - Congenital adrenal hyperplasia (CAH) is an inherited metabolic disease caused by
      the deficiency of one of the enzymes necessary for cortisol synthesis. Deficiency
      of 21-hydroxylase (21-OH) accounts for 95% of affected patients There are two
      forms of the disease. The first is classic, which may be incomplete (simple
      virilizing) or complete (salt wasting). The second is nonclassic, which may be
      symptomatic or asymptomatic. In classic 21-OH deficiency which occurs in 1:10000
      15000 live births, prenatal exposure to excess androgens results in virilisation
      of female fetus. Newborn males have normal genitalia. Postnatally, untreated
      females as well as males present with signs of androgen excess. Three fourths of
      classic 21-OH deficiency cases do not effectively synthesize aldosterone and are
      salt wasting, a condition that is potentially fatal. Nonclassic 21-OH deficiency,
      allelic variant of classic 21-OH deficiency is associated with a milder enzymatic
      defect and no genital ambiguity at birth, but postnatal virilization may be seen.
      A subset of individuals with nonclassic 21-OH deficiency are asymptomatic,
      despite high levels of androgens (cryptic form of disease). The 21-OH enzyme, a
      cytochrome P450 hemoprotein (cytochrome P450 c21) is encoded by the gene CYP21,
      which has a closely neighboring homologous pseudogene, CYP21P. Mutations in the
      CYP21 gene, causing 21-OH deficiency, are common and occur owing to two
      mechanisms: gene deletion and apparent gene conversion. Prenatal diagnosis is
      important to identify a fetus affected with 21-OH deficiency. Genital ambiguity
      in affected females can be prevented by proper administration of dexamethasone to
      pregnant mother. Postnatally, the treatment of 21-OH deficiency is lifelong
      hormonal replacement. With carefully supervised medical treatment. CAH patients
      have the capacity for normal puberty and fertility.

PMID- 8759402
TI  - [The genetics of polycystic ovaries].
AB  - The clinical characterisation of polycystic ovary syndrome (PCOS) and its
      fenotype complicate the search for its genetic causes. Still now, there is no
      concordance about the exact clinical phenotype for PCOS and there is still an
      open question whether polycystic ovaries are the necessary part of PCOS at all.
      Therefore, the author suggests to accept and follow Legro's proposal and genetic
      models in the future investigations of PCOS. Through the ethnic, familial cluster
      studies, through molecular genetic examinations and novel technology, we may be
      able to solve the problem of PCOS and find it out, how much the PCOS could be
      connected with mutations in human genome and how much could be the importance of
      environmental factors in PCOS.

PMID- 8759403
TI  - [Clinical significance of testosterone and dihydrotestosterone metabolism in
      women].
AB  - Hyperandrogenism in women refers to both excess androgen production and clinical
      manifestations of androgen excess. Clinical evaluation of women with
      hyperandrogenism is complex. The synthesis and release of androgenic steroid in
      women are normal part of adrenal and ovarian steroidogenesis. One of the classic
      questions concerning androgenic disorders concerns the source of circulating
      androgens. Relative roles of adrenal and ovary vary greatly, both can be
      involved. The use of gonadal or adrenal steroid administration can sometimes be
      used to distinguish the source of androgen excess. In many cases of
      hyperandrogenism no laboratory diagnosis of adrenal and ovarian androgen
      overproduction can be made. These patients may have increased androgen
      sensitivity due to increased enzyme 5 alpha-reductase activity in the skin. To be
      active in the skin, testosterone (T) must be converted to dihydrotestosterone
      (DHT) by the 5 alpha-reductase. The increase in DHT production is a localized
      phenomenon and there is no generalized increase in enzyme activity in women with
      hyperandrogenism. DHT is rapidly converted to other steroid metabolites including
      androsteron, androstanediol and their glucuronide and sulfate conjugates.
      Although once thought to be specific for skin conversion of T to DTH these
      androgen conjugates reflect adrenal steroid production and metabolism.
      Antiandrogens (androgen receptor blockers) are the most effective therapeutic
      modalities of cutaneous hyperandrogenism. Clinical trials are in progress to
      determine efficacy of finasteride for the treatment of hirsutism and androgenetic
      alopecia. Finasteride is the first available medication of a new class of drugs
      that is an competitive inhibitor of 5 alpha-reductase and therefore should be
      beneficial for medical treatment of cutaneous hyperandrogenism.

PMID- 8759404
TI  - [Androgen excess in women and the metabolic syndrome (syndrome X)].
AB  - In this paper we presented characteristics of insulin resistance syndrome (IRS),
      also known as metabolic syndrome and syndrome X, with an emphasis on insulin
      resistance in hyperandrogenemic women. The aim features of IRS are obesity,
      hypertension, dyslipidemia-hypertriglyceridemia and decreased HDL cholesterol,
      impaired glucose tolerance with hyperinsulinemia and higher cardiovascular
      morbidity. It is considered typical that in hyperandrogenemia, especially in PCO
      syndrome, insulin resistance and hyperinsulinemia without other characteristics
      of IRS are expressed.

PMID- 8759405
TI  - [Polycystic ovary syndrome: a disorder of insulin action and an increased risk
      for onset of non-insulin-dependent diabetes].
AB  - Hyperandrogenemia may be the most common endocrinopathy in women, affecting up to
      10% of all women and as many as 30% of certain subgroups. Women with polycystic
      ovary syndrome have a unique disorder of insulin action and are at increased risk
      to develop NIDDM. NIDDM in women with PCOS has earlier age of onset than it does
      in the general population. Insulin-induced receptor autophosphorylation is
      diminished in 50% of PCOS women. PCOS may be a disease of abnormal protein
      tyrosine kinase receptor signaling. IGF-I and IGF-II play an important role in
      regulating ovarian androgen production via receptors.

PMID- 8759406
TI  - [The effects of androgens and other sex hormones on serum lipoproteins].
AB  - This review summarizes recent data on the effects of endogenous and exogenous
      androgens, estrogens and progesterone on serum lipoproteins levels and
      composition in humans. Sex steroid hormones modulate serum lipoprotein metabolic
      mechanisms and influence atherosclerosis and coronary heart disease. In general,
      androgens lower HDL and raise LDL levels and Lp(a) thus promoting the atherogenic
      process. As it is true with estrogens, the lipoprotein effects of androgens are
      more pronounced with oral than with parenteral administration. Millions of women
      use oral contraception and postmenopausal women use more and more some form of
      hormone replacement therapy. The HDL-raising effect of estrogen replacement seems
      to be mediated by an increase in apoprotein AI production and not by a decrease
      in the clearance rate. Estrogens lower LDL levels by accelerating the rate of LDL
      catabolism which is due to an increase in the number of hepatic LDL receptors.
      They also improve endothelium-dependent vasodilatation which might be mediated by
      an antioxidant action of estrogens. These facts could explain well known
      cardioprotective effects of estrogens. Androgen progestins, especially older such
      as norgestrel, lower HDL and raise LDL thus diminishing or eliminating the
      benefits of estrogens on cardiovascular system while newer progestins have a
      lesser effect on circulating lipoproteins.

PMID- 8759407
TI  - [Insulin-like growth factors and ovarian function].
AB  - Insulin-like growth factors (IGF) are important in physiology and function of the
      human ovary. Intraovarian peptides may have a potential for local modulation of
      follicular development serving as intercellular mediator between the ovarian
      cells. IGFs constitute a family of homologous, low molecular weight, single chain
      polypeptide growth factors named for their remarkable structural and functional
      similarity to insulin. Studies have suggested its synthesis in several
      extrahepatic tissues wherein it may play autocrine or paracrine regulatory roles.
      IGF-1 stimulates DNA synthesis in human granulosaluteal cells. In synergism with
      FSH, IGF-1 stimulates aromatase activity, enhances proteoglycan biosynthesis,
      increases progesterone action. IGF-1 and IGF-2 stimulate human oocyte maturation.
      Hyperandrogenism of any type has been suggested to be due to an effect of IGFs
      mediated through their receptors or their binding proteins.

PMID- 8759408
TI  - [Polycystic ovary syndrome--Doppler parameters].
AB  - OBJECTIVE: To evaluate the value of transvaginal color and pulsed Doppler
      measurements of the uterine and ovarian arteries in infertile patients with
      polycystic ovarian syndrome (PCOS). STUDY DESIGN: Prospective controlled trial
      included forty (40) patients with PCOS and 40 healthy women. All the patients
      were examined by transvaginal color and pulsed Doppler on the 5th, 10th, 12th,
      15th, 21st and 24th day of the menstrual cycle. The hormonal profile (estradiol
      (E2), luteinizing hormone (LH), follicular stimulating hormone (FSH),
      progesterone, testosterone and prolactin) was correlated to the Doppler results.
      RESULTS: The flow velocity patterns of uterine and ovarian vessels showed changes
      during the normal ovulatory menstrual cycle, while in the patients with PCOS
      these changes did not occur. The high resistance index (RI = 1.0) with reverse
      flow was detected in both ovarian arteries in PCOS group, and showed no cyclic
      changes. Ovarian stromal and hilar arterial impedance (0.54 +/- 0.05) as well as
      uterine artery resistance index (0.91 +/- 0.09) did not show significant changes
      during the menstrual cycle. CONCLUSIONS: Our study suggests that a large fraction
      of patients suffering from PCOS has elevated uterine artery resistance index
      despite normal plasma E2 levels. It can be postulated that excessive production
      of ovarian factor (other than E2) may increase the uterine resistance and alter
      the endometrial receptivity. This finding may explain why endometrial receptivity
      is shown to be poor in patients with PCOS. Estimation of uterine and ovarian
      arterial impedance values seems to have clinical impact in the management of
      these patients attending an in vitro fertilization program.

PMID- 8759409
TI  - [Treatment of hyperandrogenemia].
AB  - Various kinds of non-hormonal or hormonal treatment of hirsutism with the
      description of medication effect spot, clinical effect and possible complications
      are described. The necessity for carrying out this therapy in combination with
      cosmetic interventions because of aesthetical reasons, as well as possible effect
      of androgenic hormones on subsequent fertility are emphasized. The effects of
      contraceptives, corticosteroides, spironolactones, ketoconazoles, GnRH agonists,
      flutamides, finasterides, somatostatine analogues, H2 receptors blockers, thyroid
      gland hormones and cyproterone acetates are shown.

PMID- 8759410
TI  - [Acne, hirsutism and androgenic alopecia].

PMID- 8759411
TI  - [Tests of adrenal gland and ovarian function in the hyperandrogenemia syndrome].
AB  - Androgen production in women is under the influence of pituitary hormones on
      ovaries and adrenal glands, or they originate from peripheral conversion of
      androgen precursor. Each of the three principal compartments of androgen
      production has a serum specific marker that may be clinically helpful. Serum
      testosterone signifies ovarian production, dehydroepiandrosterone sulfate (DHA-S)
      is an adrenal marker, and serum 3 alpha-diol glucuronide reflects androgen action
      in the peripheral compartment. Many physiologic and pathologic states affect
      transport proteins and enzyme systems which modulate androgenic activity. This
      fact makes the determination of mechanism and origin of hyperandrogenemia more
      difficult, as well as the choice of therapy. In the syndrome of
      hyperandrogenemia, the primary place of the disorder is determined by the tests
      of adrenal cortex and ovary functions. The correct response of androgens in
      dexamethasone test is manifested by free testosterone suppression to < 0.028
      nmol/L, and by DHA-S and plasma cortisol suppression under the reference values.
      In the complex and controversial syndrome of hyperandrogenemia, the nafarelin
      test is used after insufficient free testosterone suppression in dexamethasone
      test. The significant diagnostic criterion is the rise of 17-hydroxyprogesterone
      (17-OHP) over 7 nmol/L, which aligns a great number of idiopathic
      hyperandrogenemias in the group of polycystic ovary syndrome. A good correlation
      was found between the rise of 17-OHP in nafarelin test and the suppression of
      free testosterone in dexamethasone test. This finding supports the conception
      that both tests determine the ovary function and that their sensitivity and
      specificity for ovary hyperandrogenemia is comparable.

PMID- 8759412
TI  - [Hyperinsulinemia and arterial hypertension].
AB  - Data concerning hyperinsulinemia/insulin resistance in the pathogenesis of
      essential hypertension are presented. Approximately 50% of hypertensive patients
      have insulin resistance. The prime site of insulin resistance is in the skeletal
      muscle affecting non oxidative glucose metabolism (glycogen synthesis). Effects
      of insulin on the kidney points toward possible, but not the key role of the
      hyperinsulinemia in the pathogenesis of arterial hypertension. According to some
      results hypertension causes hyperinsulinemia/insulin resistance through
      hemodynamic alterations and structural changes of blood vessels. On the other
      hand, there is no hyperinsulinemia in the secondary forms of arterial
      hypertension. This is an argument against hypertension as a prime cause in
      insulin resistance inception. The importance of metabolic alterations of lipid
      status and fibrinolytic system in patients with hyperinsulinemia has been
      emphasized. These metabolic changes increase cardiovascular risk. Effects of
      antihypertensive drugs on glucose metabolism and insulin sensitivity are
      reported. In conclusion, hyperinsulinemia per se is not a risk factor. However,
      when connected with other metabolic disturbances (dyslipidemia, hypertension,
      hyperuricemia, disorders of fibrinolysis) it increases the risk of cardiovascular
      diseases.

PMID- 8759413
TI  - [National organization of health care in diabetes based on the "Croatian model"].
AB  - This review article shows the development and organization of the "Croatian
      Model" of organization of health care for diabetic patients from Professor Vuk
      Vrhovac to this day, and its inclusion in the St. Vincent Declaration-a group of
      recommendations agreed upon in 1989 with the aim to decrease the morbidity and
      mortality of diabetes and its complications. The Model is organized on primary,
      secondary and terciary levels of health care. After the administrative changes of
      1993, specialized health care for diabetic patients is delivered through County
      and Regional Centres for Diabetes and the Diabetes Reference Centre (the Vuk
      Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases), a scientific
      and educational institution and a WHO Collaborating Centre. Mention is made of
      the Croatian Diabetes Registry and statistical data on the morbidity (the
      prevalence of diabetes in Croatia is 2.37%) and mortality of diabetes mellitus
      and its complications, of organization of health care for diabetic patients,
      their medical treatment and care in Croatia.

PMID- 8759415
TI  - [Mucolipidosis type III (case report)].
AB  - A six-year-old boy with mucolipidosis type III or pseudo Hurler polydystrophy is
      described. The disease is manifested by multiple progressive joint contractures,
      especially of fingers, presenting as claw hands. The diagnosis of mucolipidosis
      was established after exclusion of rheumatoid arthritis and
      mucopolysaccharidosis. In serum and medium of cultured skin fibroblasts, high
      catalytic activities of several lysosomal enzymes with strikingly decreased
      values in fibroblast homogenate were found. In most lysosomal diseases gene
      mutations cause reduced or absent activity of a specific enzyme. In mucolipidosis
      type III, a basic biochemical disorder is the absence of mannose-6-phosphate, a
      marker that enables lysosomal membrane receptors to recognize lysosomal enzymes.
      The transport of lysosomal enzymes across the lysosomal membrane is therefore
      defective. These and several other metabolic diseases are thus categorized as the
      disorders of the lysosomal enzyme transport. A genetic and biochemical
      heterogeneity, as well as clinical manifestations, are described in more detail.

PMID- 8759414
TI  - [Biochemical changes in hypertensive patients during a 1-year cross-over study of
      treatment with hydrochlorothiazide and propranolol].
AB  - A prospective, randomized, cross-over trial comparing the antihypertensive
      efficacy and biochemical changes during treatment with either hydrochlorothiazide
      (HTZ: 25 mg o.d.) or propranolol (PRO: 40 mg t.i.d.), included 55 mild to
      moderate hypertensives (diastolic blood pressures ranged from 90 to 110 mmHg),
      aged 25-65 years. Forty patients completed the study; during the first six months
      20 of them (12 males and 8 females) were taking HTZ, and the remaining 20 (13
      males and 7 females) PRO. After a one-week wash-out period, for the next six
      months the alternative drug was administered. Antihypertensive efficacy of both
      drugs was nearly equal: systolic and diastolic blood pressure significantly
      decreased already after the first month (approximately by 10%), and kept
      unchanged until the end of the study. The analyzed biochemical parameters, i.e.
      blood glucose, cholesterol, and triglycerides did not increase significantly,
      while serum potassium level remained almost unchanged during the trial.
      Furthermore, during PRO in group B, cholesterol significantly decreased (3rd
      month), as well as blood glucose during HTZ treatment (10th month). Only the uric
      acid level, although unsignificantly, increased in group A (from 326.2 to 365.3
      +/- 125.2 on HTZ, and to 391.4 +/- 120.0 mumol/l on PRO). It is concluded that
      HTZ and PRO are comparably effective antihypertensives. During the long-term
      treatment in small doses these drugs do not induce significant biochemical
      disturbances.

PMID- 8759416
TI  - [The Klippel-Trenaunay syndrome].
AB  - The article presents the Klippel-Trenaunay syndrome. The diagnosis was set upon
      birth based on typical skin angiomatous nevi and hypertrophy of soft tissue and
      bones. Later on, the patient also developed the third element of the syndrome,
      i.e. varicose veins. The patient has a rare form of the disease, with hypertrophy
      of soft tissue in the left forearm and soft tissue and bones of his right leg.
      The static type macrodactylia is present on both hands and feet. The paper gives
      clinical description of this rare, nonhereditary disease. The need of continuous
      multidisciplinary monitoring of such patients is emphasized, since this syndrome
      should be distinguished from Parkes Weber syndrome which has essentially
      different prognosis.

PMID- 8759417
TI  - [Fatal "overwhelming" strongyloidiasis in an immunosuppressed patient].
AB  - The increased use of immunosuppressants in the treatment of malignant and non
      malignant diseases in today's medicine has significantly contributed to the
      increased interest in infections caused by opportunistic microorganisms and rare
      parasites. A fifty-eight-year old male patient, professor, born in Bosnia, was
      admitted to the Institute due to poor general condition and decompensated steroid
      diabetes. He had been under immunosuppressant therapy for the previous 5 weeks.
      Six months before, he noticed squamous and crusted changes on capilli, and
      afterwards on his body too. As these changes did not respond to local therapy he
      was admitted to the Department of Dermatovenereology, Zagreb University School of
      Medicine. Histologic analysis indicated pemphigus erythematosus. He was treated
      with immunosuppressants (methylprednisolone + azathioprine). Endoscopic
      examinations revealed duodenal ulcer, in addition to diabetes which could not be
      regulated by oral hypoglycemics. He received antiulcerative therapy for ulcer
      treatment. Several hours upon admission the patient became highly febrile, and
      vomited a sanguinolent content. In spite of intensive therapy, he became comatose
      and died 20 hours later. On autopsy, generalized strongyloidosis of the lungs,
      liver, duodenum and small intestine, and a bleeding duodenal ulcer due to
      strongyloidosis were found. This review should remind us that hyperinfestation
      with strongyloides is a rare and severe complication, and could be expected in
      immunocompromised patients.

PMID- 8759418
TI  - [Reconstruction of the cervical esophagus with free autotransplantation of the
      jejunum--direct monitoring of viability].
AB  - Although free jejunum transfer has become an accepted form of hypopharyngeal
      reconstruction, an ideal method of monitoring the viability of the graft has not
      been devised yet. The method of direct visualisation through the incision in the
      skin above the transferred jejunum has proven very reliable and easy to perform,
      especially for the nursing staff. This reliable method of monitoring free
      vascularised jejunum to the neck region has been used in two patients. After two
      days of direct monitoring, the incision in the skin healed without additional
      sutures. No failures of the graft occurred, and 12 days later the patients were
      able to swallow fluids without difficulty. The effectiveness of this technique
      has surpassed that of all previously published methods.

PMID- 8759419
TI  - [Does the Lich-Gregoir antireflux procedure belong to the past?].
AB  - The Lich-Gregoir antireflux surgical procedure was applicable in 166 children and
      adolescents with primary vesicoureteric reflux of all grades. In these patients
      we have done 275 antireflux plastics and reflux was cured in 97.8% operated
      ureters. This procedure is not applicable in patients with grossly dilated
      ureters on the excretory urogram, but gives highgrade success in all others
      cases. The operation is extravesical, with minimal risk of damaging urinary
      structures and adjacent tissue, and is simple to perform. The patients recover
      quickly and easily. This practical and safe antireflux operative method has been
      unduly neglected and it has its place in the future.

PMID- 8759420
TI  - [Anorexia nervosa].
AB  - Anorexia nervosa is a very serious and potentially lethal eating disorder. It is
      characterized by distorted body picture, obsession with thinness, and loss of
      body weight exceeding 15% of expected ideal body weight. The incidence of this
      disorder is increased and the earlier the diagnosis and therapy start, the better
      is the prognosis. Etiology is unknown, but biological, social and psychological
      factors are assumed. The clinical picture is characterized by loss of body
      weight, amenorrhea, opstipation, sensitivity to cold, dry skin, exhaustion and
      obsession with the fear of becoming fat. Some laboratory findings are deranged,
      especially electrolyte balance. Hormonal derangement is also found. Diagnosis is
      made according to ICD 10, or DSM IV diagnostic criteria. In differential
      diagnosis, distinction has to be made from many somatic and some psychiatric
      disorders. Generally, somatic complications indicate the treatment, first in
      hospital and later on the outpatient basis. In the treatment, special attention
      should be paid to simultaneous application of pharmacotherapy and psychotherapy
      in order to ensure better prognosis, which is usually poor.

PMID- 8759421
TI  - [Disorders of clearance of pollutants from the lung].
AB  - Mechanisms of elimination of pollutants from the lungs are described. Factors
      which might produce deleterious effects on elimination of pollutants are listed.
      Changes of mucociliatry clearance and phagocytosis under the influence of general
      atmospheric pollutants, cigarette smoke, pharmacologic preparations, immunologic
      system, occupational exposures, and other effects are presented.

PMID- 8759422
TI  - [Dihydropyridine: what is the status today?].

PMID- 8759423
TI  - [The role of arterial hypertension in the progression of chronic renal failure].

PMID- 8759424
TI  - Dealing with heat stress.

PMID- 8759425
TI  - On-line detection of glutamate release from cultured chick retinospheroids.
AB  - A continuous fluorometric assay was adapted to measure the release of endogenous
      glutamate from cultured chick retinospheroids. The results obtained with this
      technique are compared with the release of [3H]D-aspartate from monolayer
      cultures of chick retina cells. It is shown that although excitatory amino acids
      may be released in a Ca(2+)-dependent manner, most of the neurotransmitter
      release from cultured retina cells occurs by reversal of the glutamate
      transporter. The presence of extracellular Ca2+ may actually inhibit glutamate
      release by the cells present in the retinospheroids, or the [3H]D-aspartate
      release by cells in monolayers, when veratridine is the depolarizing agent.

PMID- 8759427
TI  - c-fos gene expression in postnatal rat retinas with light/dark cycle.
AB  - We examined the diurnal variation of c-fos gene expression during a 12:12
      light/dark cycle in developing rat retinas by in situ hybridization
      histochemistry. c-fos Gene was not expressed before postnatal day 10 (P10) but
      was expressed on P15 in the outer nuclear layer throughout the dark period and in
      the inner nuclear layer and the ganglion cell layer during the light period.
      These results demonstrated that the earliest c-fos gene expression occurred
      between P11 and P15. The good correlation between the expression of c-fos gene
      and the genes coding for proteins involved in phototransduction, in terms of
      their diurnal variation and in their development, suggested that c-fos gene may
      play a role in the regulation of these genes in retinal cells during the
      light/dark cycle.

PMID- 8759426
TI  - Effects of excitatory amino acids on phosphoinositide metabolism in frog retina.
AB  - The effects of excitatory amino acid receptor agonists on the hydrolysis of
      phosphoinositides were examined using frog retinal membranes prelabeled in vitro
      with either 32PO4 or [3H]inositol. Glutamate stimulated release of [3H]inositol
      phosphates (IPs) from the retinas and altered the 32P-labeling pattern of
      phosphatidylinositol (PI) cycle intermediates. This indicates that glutamate
      affects not only the hydrolysis of phosphoinositides but possibly other steps
      involved in the PI cycle. Among glutamate analogs, kainate (KA), quisqualate
      (QA), and, to a lesser extent, N-methyl-D-aspartate (NMDA) mimicked the glutamate
      effect, whereas L-2-amino-4-phosphonobutyrate (L-AP4) was not effective in
      causing either the accumulation of [3H]IPs or the alteration of the 32P-labeling
      pattern of PI cycle intermediates. Among QA specific agonists, alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionate (AMPA), but not ibotenate (IBO) or trans-1
      aminocyclopentane-1,3-dicarboxylate (ACPD) was active in stimulating IPs
      formation. KA effect on IPs formation may be due to indirect (polysynaptic)
      activation of receptor(s) other than L-AP4, IBO, or ACPD specific QA receptors.
      To avoid activating polysynaptic pathways, retinal synaptoneurosomes prelabeled
      with [3H]inositol were used to examine the hydrolysis of phosphoinositides. As in
      whole retinas, KA, carbachol (CARB), and NMDA stimulated the release of IPs while
      L-AP4 had minimal effect. Glycine (GLY) had no effect. Our results show CARB and
      KA to be the most effective in stimulating the production of IPs. Their effects
      were exerted directly through separate receptors and not through polysynaptic
      pathways. ACPD and IBO were the least effective in eliciting the release of IPs.
      Our studies provide evidence that ionotropic and not metabotropic glutamate
      receptors are involved in PI metabolism in the retina.

PMID- 8759428
TI  - Identification of retinolisomers by high-performance liquid chromatography not
      unequivocal up to now.
AB  - Former publications dealing with high-performance liquid chromatography (HPLC) of
      retinol provide inconsistent results and lack evidence for the identification of
      isomers. For clarification of the problems in this field, the isomeric structure
      of the major retinol isomers in crystallized form was proven by 1H-NMR, UV
      absorption spectroscopy and by X-ray analysis. These identified isomeric forms of
      retinol were separated by HPLC with different eluent mixtures and the
      chromatograms compared in detail with previously published data. A conclusive
      assignment for HPLC separation of retinol isomers is given.

PMID- 8759429
TI  - Brightness induction from uniform and complex surrounds: a general model.
AB  - We studied the brightness induced from complex non-figural achromatic surrounds.
      A spatially uniform test field was surrounded by a random texture composed of two
      sets of dots. The luminance of each set of dots was modulated sinusoidally at 0.5
      Hz. The mean luminance, phase and amplitude of modulation of each set were
      controlled independently so as to modulate the luminance and/or the contrast of
      the surround. Brightness induction was measured by a modulation nulling
      technique. The results were fit by a model in which the total brightness induced
      by a surround is equal to a weighted spatial summation of the induced effects
      from each point in the surround. The model incorporates local luminance gain
      controls in the test and surround fields and assumes that the magnitude of
      induction from each surround element is gain controlled by the difference between
      the mean luminance of the test and the individual surround elements.

PMID- 8759430
TI  - Fourier and non-Fourier pattern discrimination compared.
AB  - Various studies indicate the existence of non-Fourier visual mechanisms that can
      extract non-luminance cues (e.g., contrast modulation) as well as a Fourier
      mechanism that deals with luminance variation only. We compared the pattern
      discrimination performance of the non-Fourier mechanism with that of the Fourier
      mechanism by using orientation discrimination and spatial-frequency
      discrimination tasks. The Fourier patterns used were D6s, the sixth spatial
      derivative of a Gaussian function multiplied by another Gaussian function in the
      orthogonal dimension. The corresponding non-Fourier patterns were D6 contrast
      modulated cosine gratings. Our results showed a similar trend for the non-Fourier
      and the Fourier performance at various peak spatial-frequencies or orientations
      of D6. However, the discrimination threshold of the non-Fourier mechanism was
      about two-fold higher than that of the Fourier mechanism. The oblique effect was
      also stronger for non-Fourier patterns. In addition, worse performance for non
      Fourier patterns at short stimulus durations (around 33.3 msec) was consistent
      with the prediction of the two-stage non-Fourier model, which requires more time
      for the additional rectification and filtering operations.

PMID- 8759431
TI  - Relative size disparities and the perception of surface slant.
AB  - Perceived slant produced by size disparities in random-dot displays was measured
      by tactile matching. For a 60 deg surface, slant produced by vertical-size
      disparity (the induced effect) was opposite to that produced by horizontal-size
      disparity. Overall-size disparity produced a little slant. With small displays,
      effects of horizontal and vertical disparities were reduced but not those of
      overall disparity. A zero-disparity surround increased effects of horizontal and
      overall disparities but reduced the induced effect. A mixture of horizontally
      disparate and zero-disparity dots produced two slanted surfaces. Vertically
      disparate and zero-disparity dots produced one slanted surface. Abutting opposite
      horizontal disparities produced surfaces with a sharp boundary. Abutting vertical
      disparities produced surfaces with a gradual boundary. Perceived slant depends on
      the difference between horizontal-size disparity detected locally and mean
      vertical-size disparity over a relatively large area.

PMID- 8759432
TI  - Responses to opposed directions of motion: continuum or independent mechanisms?
AB  - Opponency between opposite directions of motion is a characteristic of many
      models of movement detection and is commonly invoked in explanations of the
      motion after-effect. If detection of opposite directions is mediated by a single
      mechanism, then a single, smooth psychometric function for the discrimination of
      global direction in random-dot kinematograms should be found as a function of the
      percent of directional coherence of dots in the display, ranging from 100%
      coherence leftwards through 0% coherence to 100% coherence rightwards. Moreover,
      after rightward motion adaptation, a single psychometric function should still be
      observed if adaptation affects the perceptual system prior to opponent
      interactions. If, however, leftward and rightward detectors operate
      independently, then the slopes of the leftward and rightward halves of the
      function may differ, particularly after unidirectional adaptation. We measured
      the probability of a "rightward" direction response for nine values of motion
      coherence for five observers with and without prior rightward motion adaptation.
      Although a smooth psychometric function was found without motion adaptation,
      after adaptation, the rightward half of the psychometric function was flattened
      whereas the leftward half remained unchanged. Such results indicate that movement
      direction analysers operate in a non-opponent manner.

PMID- 8759433
TI  - Better performance through amblyopic than through normal eyes.
AB  - Spatio-temporal interpolation reconstructs the (complete) motion path of objects
      presented discontinuously, e.g. under stroboscopic illumination or in television.
      Interpolative vernier stimuli were created by presenting two line segments with a
      temporal delay instead of a spatial offset. Ten amblyopic patients had to
      indicate whether the lower segment of the moving target was offset to the left or
      right relative to the upper segment. For five patients we also measured
      thresholds for a conventional moving vernier. Five normal subjects were measured
      with sharply focused and blurred interpolative verniers. At low velocities of
      interpolative vernier targets, results of amblyopic eyes are inferior to those of
      normal eyes. However, 9 out of 10 patients perform better using their amblyopic
      than using their normal eye at high velocities. In control subjects, blurred
      stimuli yield results similar to those of amblyopic eyes, indicating a similarity
      between (optical) blur and the mechanisms underlying amblyopia. Thresholds for
      conventional vernier targets of amblyopic observers, on the other hand, are
      constant over the whole velocity range for both normal and amblyopic eyes, with a
      better performance of the normal eye at all velocities. The consequences for
      models of amblyopia are discussed.

PMID- 8759434
TI  - Development of grating acuity and contrast sensitivity in the central and
      peripheral visual field of the human infant.
AB  - Central and peripheral visual functions were measured simultaneously in 39
      infants from 10 to 39 weeks old using a dual-frequency VEP technique. Central
      acuity and contrast sensitivity over a 4 deg circular field were measured at 6 or
      8 Hz. Peripheral acuity and contrast sensitivity were measured simultaneously at
      the other rate with a semi-circular stimulus extending from 8 to 16 deg. The EEG
      was analyzed at 12 and 16 Hz to determine the separate responses for the central
      and peripheral fields. Both central and peripheral VEP acuity developed over the
      age range tested. Central acuity improved by about a factor of 2.6 over the age
      range tested, while peripheral acuity improved by about a factor of 2.2. Central
      acuity was always higher by an average factor of about 2.3. Contrast sensitivity
      showed similar development for the central and peripheral fields with an early
      rapid rise in sensitivity.

PMID- 8759435
TI  - The time course of 2-D shape discrimination in random dot stereograms.
AB  - Predictions of a coarse-to-fine and co-operative stereo matching algorithm were
      compared using a 2-D shape discrimination task for disparity-defined targets in
      50% random dot stereograms. Uniform disparity targets, square wave modulated
      targets with a different mean disparity to the background, or uncorrelated dots
      could be seen at much briefer exposures (down to 33 msec) than square wave
      modulated targets with the same mean disparity as the background. In the latter
      case, performance at brief exposures was improved by using coarser disparity
      corrugations. The results are readily explained by a coarse-to-fine matching
      scheme such as that proposed by Marr & Poggio (1979) [Proceedings of the Royal
      Society of London (B), 204, 301-328] and suggest that the correspondence problem
      is not the limiting step in the perception of simple cyclopean forms.

PMID- 8759436
TI  - Stereoscopic depth perception and vertical disparity: neural mechanisms.
AB  - The additivity assumption relates to the various stereo-disparity components in
      the vertical and horizontal meridians, each of which is assumed to be independent
      of the other, with the total disparity in each dimension being the linear sum of
      the separate components. Information about the position of the eyes provided by
      the corollary discharge leads to compensatory changes in the lateral geniculate
      nuclei whereby the angle of gaze disparity component at retinal level is offset
      by equal and opposite changes at geniculate level. These geniculate changes
      concern only eye position. Changes in the retinal images such as those produced
      by lenses (i.e. induced effect) are passed on to the cortex without modification
      at the geniculate level. Discrimination of the local depth disparity component
      can be achieved by subtracting the local vertical eccentricity component from the
      total horizontal disparity.

PMID- 8759437
TI  - Decreases in the latency of smooth pursuit and saccadic eye movements produced by
      the "gap paradigm" in the monkey.
AB  - The initiation of both pursuit and saccades was affected by the presence of a
      temporal gap between the disappearance of a fixated visual target and the
      appearance of a second, eccentric, target. For pursuit, the gap paradigm produced
      a modest (20 msec) decrease in latency. For saccades, the gap paradigm produced a
      similar modest decrease in the latency of some saccades, but also revealed a
      population of very short latency "express" saccades. The modest changes in the
      latency of pursuit and regular saccades displayed a similar dependence on gap
      duration, with the largest decreases produced by gaps of 200-300 msec. The gap
      paradigm did not produce "express" pursuit, even though express saccades could be
      elicited on interleaved trials.

PMID- 8759438
TI  - A novel method for measuring saccade profiles using the scanning laser
      ophthalmoscope.
AB  - Most existing techniques for accurately measuring angular eye position vs time
      during a saccade (the saccade profile) need either contact to the eye or are
      restricted in time resolution. In this paper we introduce a new noninvasive
      method, with high spatial and temporal resolution, for determining saccade
      profiles using a scanning laser ophthalmoscope (SLO). This method uses the fact
      that images of a moving object taken with the SLO are not blurred (as are images
      from video cameras) but show a tilt with respect to images of the same stationary
      object. A mathematical framework is given that allows determination of a saccade
      profile from a restricted number of consecutive SLO video fields of the fundus
      during a saccade. The angular resolution obtained by this method is below 0.1
      deg, and the maximum time resolution near 1 msec. Measured saccade profiles could
      be well approximated by a gamma function, the first derivative of which yields
      the saccade velocity profile. Measurements of peak saccade velocity as a function
      of saccade amplitudes (main sequence) using our method show good agreement with
      results obtained by other authors.

PMID- 8759439
TI  - Losses in peripheral colour sensitivity predicted from "hit and miss" post
      receptoral cone connections.
AB  - On the basis of the early primate neurophysiological recordings, it was thought
      that the different cone types of the primate retina project selectively into the
      centre and surround of the receptive fields of cone opponent neurons, and more
      recently this view has been reasserted on the basis of physiological results. An
      alternative idea is that these projections are in fact unselective for cone type,
      and, therefore, cone opponency arises from chance variations in the proportions
      of different cone types in centre and surround. The issue is presently
      controversial with anatomical or physiological support for both hypotheses. Our
      results show that there is a selective loss of red-green colour sensitivity
      across the human visual field. Furthermore, this selective loss occurs under low
      temporal frequency conditions (0.5 Hz) which were selected to favour the
      mediation of both colour and luminance detection by a common P cell pathway and
      to exclude an M cell contribution to detection threshold. We show that "hit and
      miss" post-receptoral cone projections will produce a decline in cone opponency
      that is sufficient to account for this selective loss, thus providing
      psychophysical evidence consistent with this hypothesis.

PMID- 8759440
TI  - Sex differences in macular pigment optical density: relation to plasma carotenoid
      concentrations and dietary patterns.
AB  - Sex differences in macular pigment (MP) optical density (measured
      psychophysically) were examined. Concentrations of lutein and zeaxanthin (L and
      Z) (non-separated) and beta-carotene (BC) in the blood were determined using
      reverse phase high-performance liquid chromatography. Dietary intake of L and Z,
      BC, fat, and iron were estimated by questionnaire. Males had 38% higher MP
      density than females (P < 0.001) despite similar plasma carotenoid concentrations
      and similar dietary intake (except for fat). Dietary intake of carotenoids, fat
      and iron, as well as plasma concentrations of L and Z were positively related to
      MP density in males. Conversely, only plasma L and Z was related to MP density
      for females, and dietary fat was negatively related to MP density. Sex
      differences in protection of the retina by MP and in the relationship between the
      retina, blood and diet could be a factor in the incidence of retinal diseases,
      especially age-related macular degeneration.

PMID- 8759441
TI  - Reconstruction of retinal horizontal cell responses by the ionic current model.
AB  - An ionic current model of the retinal horizontal cell is constructed. The
      horizontal cell models are interconnected by gap junctions to form a horizontal
      cell layer. The light response properties of the L-type horizontal cell are
      analyzed using this model. We demonstrate the functional role of each ionic
      current and the role of the feedback loop between cones and horizontal cells. The
      present study provides insight into the dynamic relationships between
      characteristics on the cellular level and on the multi-cellular level for
      producing the light response in horizontal cells.

PMID- 8759442
TI  - Angle judgement: is the whole the sum of its parts?
AB  - This study concerns whether the discrimination of a geometric angle depends on
      the orientations of its bounding lines or on angle size. In Experiment 1,
      thresholds for angle discrimination were measured in three observers for angles
      ranging from 15 to 180 deg, oriented either vertically or obliquely. Angle
      discrimination thresholds were found to depend primarily on angle size for most
      of the range of angles (angle-dependent, or Weber's law regime). However, in a
      small region near 90 deg (orientation-dependent regime) angle discrimination
      depends on the orientations of the bounding lines. When our data in the angle
      dependent regime were fitted with a power function, the exponents were close to
      or < 0.5, suggesting that a step-increment approach was used to calculate angle.
      In Experiment 2, orientation discrimination thresholds for lines corresponding to
      the bounding lines of the vertically and obliquely oriented 15, 90 and 165 deg
      angles were measured. Confirming previous studies, a strong meridional anisotropy
      in line orientation discrimination was found for all three observers. The
      orientation discrimination thresholds were then used to predict the
      discrimination thresholds for the corresponding angles based on a simple
      statistical model. The predicted angle discrimination thresholds were worse than
      those measured empirically except for the titled 90 deg angles. This result
      indicates that angle discrimination thresholds are not limited by the same noise
      as orientation discrimination for most angles except for the tilted 90 deg angle,
      where the limiting factor may be the precision in determining the orientations of
      the bounding lines. In Experiment 3, we show that angle discrimination is quite
      robust to small amounts of orientation jitter, suggesting that angle judgments
      are made at a level beyond the early filter representation.

PMID- 8759443
TI  - Undersampling produces non-veridical motion perception, but not necessarily
      motion reversal, in peripheral vision.
AB  - We investigated motion perception in peripheral vision (10-40 deg eccentricity)
      for drifting gratings above and below the Nyquist limit set by neural sampling of
      the retinal image. We found that psychometric functions for motion discrimination
      rarely exhibited worse-than-chance performance indicative of motion reversal. A
      series of control experiments indicated that failure to demonstrate motion
      reversal could not be attributed to: (1) failure to detect the contrast of the
      stimulus; (2) failure to detect the motion of the stimulus; (3) use of an
      inappropriate range of spatial frequencies. Although consistent motion reversal
      was not observed, additional experiments demonstrated that motion perception was
      nevertheless non-veridical for spatial frequencies above the Nyquist limit. These
      seemingly contradictory results were reconciled by the observation that aliased
      patterns could appear to move in several different directions, all of which were
      different from the direction of stimulus, but only of which was opposite to the
      stimulus direction. Nyquist limits inferred from motion discrimination lie near
      the predictions for P-ganglion cells in human retina and well above M-cell
      predictions, which implies the M-cell array is too sparse to account for the
      limits to verdical motion perception in peripheral vision.

PMID- 8759444
TI  - Perceived texture segregation in chromatic element-arrangement patterns: high
      intensity interference.
AB  - An element-arrangement pattern is composed of two types of elements that differ
      in the ways in which they are arranged in different regions of the pattern. We
      report experiments on the perceived segregation of chromatic element-arrangement
      patterns composed of equal-size red and blue squares as the luminances of the
      surround, the interspaces and the background (surround plus interspaces) are
      varied. Perceived segregation was markedly reduced by increasing the luminance of
      the interspaces. Perceived segregation was approximately constant for constant
      ratios of interspace luminance to square luminance and increased with the
      contrast ratio of the squares. Unlike achromatic element-arrangement patterns
      composed of squares differing in lightness [Beck et al (1991). Vision Research,
      32, 719-743] perceived segregation did not decrease when the luminance of the
      interspaces was below that of the squares. Similar results were obtained for red
      and yellow, red and green, green and yellow, green and blue, and blue and yellow
      squares. Perceived segregation based on edge alignment was not interfered with by
      high intensity interspaces. Stereoscopic cues that caused the squares composing
      the element-arrangement pattern to be seen in front of the interspaces did not
      greatly improve perceived segregation. One explanation of the results is in terms
      of inhibitory interactions among achromatic and chromatic cortical cells tuned to
      spatial frequency and orientation. Alternately, the results may be explained in
      terms of how the luminance of the interspaces affects the grouping of the squares
      for encoding surface representations. Neither explanation accounts fully for the
      data and both mechanisms may be involved.

PMID- 8759445
TI  - Face recognition under varying poses: the role of texture and shape.
AB  - Although remarkably robust, face recognition is not perfectly invariant to pose
      and viewpoint changes. It has long been known that both profile and full-face
      views result in poorer recognition performance than a 3/4 view. However, little
      data exist which investigate this phenomenon in detail. The present work provides
      such data using a high angular resolution and a large range of poses. Since there
      are inconsistencies in the literature concerning these issues, we emphasize the
      different roles of the learning view and the testing view in the recognition
      experiment. We also emphasize the roles of information contained in the texture
      and in the shape of a face. Our stimuli were generated from laser-scanned head
      models and contained either the natural texture or only Lambertian shading and no
      texture. The results of our same/different face recognition experiments are: (1)
      only the learning view but not the testing view affects recognition performance.
      (2) For textured faces the optimal learning view is closer to the full-face view
      than for the shaded faces. (3) For shaded faces, we find a significantly better
      recognition performance for the symmetric view. The results can be interpreted in
      terms of different strategies to recover invariants from texture and from
      shading.

PMID- 8759446
TI  - Direction-selective adaptation and simultaneous contrast induced by stereoscopic
      (cyclopean) motion.
AB  - Across four experiments, this study investigated direction-specific adaptation
      and simultaneous contrast induced by moving binocular disparity information
      (stereoscopic motion). The stimuli were moving arrays of stereoscopic dots
      created from dynamic random-element stereograms. Experiments 1 and 2 examined the
      effects of adaptation to motion in a given direction on the apparent direction of
      test motion. Results showed that the direction of test motion appeared repulsed
      away from the direction of adapting motion (repulsion aftereffect) by as much as
      20 deg or more when directions of adapt and test were similar. Experiment 3
      investigated transfer of the repulsion aftereffect across the stereoscopic and
      luminance domains by employing stereoscopic adapting motion and luminance test
      motion or vice versa. Results showed that the repulsion aftereffect transferred
      across the two stimulus domains. Experiment 4 investigated direction-specific
      contrast by measuring the perceived direction of two stereoscopic arrays
      presented simultaneously and moving in different directions. Results showed that
      the directions of the arrays appeared repulsed away from one another when their
      directions were similar. Taken together, these results suggest that the direction
      of stereoscopic motion is coded in the activity of directionally selective
      mechanisms, as is the case for luminance-domain motion. Transfer of the repulsion
      aftereffect between stereoscopic and luminance domains indicates the two kinds of
      motion perception are mediated by a common substrate.

PMID- 8759447
TI  - Brightness contrast from inhomogeneous surrounds.
AB  - The luminance of a test within an inhomogeneous ("checkerboard") surround was
      adjusted to match the brightness of a comparison patch within a uniform surround.
      All stimuli were achromatic. Both surrounds had the same space-averaged
      luminance. With an incremental comparison patch, a test-within-checkerboard at a
      luminance between the luminances of the brighter and dimmer checks appears dimmer
      than if viewed within the uniform surround. A decremental comparison patch,
      however, is matched by a test luminance that is little affected by the
      inhomogeneity of the surround. In general, the brightness of the test is mediated
      neither by the space-averaged luminance of an inhomogeneous surround, nor by any
      equivalent uniform surround, regardless of luminance. We consider alternative
      models for the brightness of a region that is neither strictly an increment nor
      decrement with respect to contiguous surrounding surfaces.

PMID- 8759448
TI  - Spatial frequency adaptation: threshold elevation and perceived contrast.
AB  - We have measured the spread of contrast adaptation across the dimension of
      spatial frequency. Threshold elevation was tightly tuned to the adapting spatial
      frequency but became much broader as test contrast was increased. This means
      that, for a given test frequency, there are some frequencies which do not raise
      threshold but do result in a loss of perceived contrast. The contrast dependence,
      retinal specificity and interocular transfer of adaptation effects elicited from
      same-and remote-frequency adaptation were compared. While we were able to show
      some distinct differences between threshold and suprathreshold tests, we were
      unable to demonstrate any reliable differences in the retinal specificity and
      interocular transfer between same- and remote-frequency adaptation.

PMID- 8759449
TI  - Perceived contrast following adaptation to gratings of different orientations.
AB  - Using a contrast matching procedure, we measured the perceived contrast of
      vertical test gratings after adapting to other gratings of either vertical or
      horizontal orientation. The results show that both parallel and orthogonal
      adapting gratings reduce perceived contrast and do so proportionally more at low
      test contrasts than at high. The results are consistent with a single mechanism
      model proposed by Ross and Speed [(1991). Proceedings of the Royal Society
      (Series B), 246, 61-69] that assumes that adaptation to gratings repositions
      contrast-response transducer functions. They are not consistent with the notion
      of two different forms of adaptation, subtractive for parallel and multiplicative
      for orthogonal adaptors as proposed by Snowden and Hammett [(1992). Nature, 355,
      248-250]. Nowhere is the reduction in perceived contrast by an orthogonal grating
      greater than that by a parallel grating of the same contrast. A direct comparison
      using two orthogonal adaptors confirms the greater potency of parallel adaptors,
      but also reveals interactions between the adaptors.

PMID- 8759450
TI  - Speed discrimination under stabilized and normal viewing conditions.
AB  - To determine whether speed discrimination improves when the retinal image is
      stabilized against the effects of eye movements, thresholds were measured under
      stabilized and normal viewing conditions. In the normal viewing conditions, eye
      movements were recorded and used to estimate retinal-image speeds. Stimulus
      reference speed for sinusoidal gratings varied from 0.5 to 8.0 deg/sec. Results
      showed that speed discrimination thresholds, expressed as Weber ratios, decreased
      with increasing stimulus speed for both the normal and stabilized viewing
      conditions. Stabilized viewing thresholds were higher than normal viewing
      thresholds only at the slowest stimulus reference speed. However, when speed
      discrimination thresholds were expressed as a function of the estimated retinal
      speed, there was no difference in thresholds for the stabilized and normal
      viewing conditions. A retinal-image model, whereby speed discrimination depends
      on retinal-image motion, explains the results.

PMID- 8759451
TI  - Saccade target selection and object recognition: evidence for a common
      attentional mechanism.
AB  - The spatial interaction of visual attention and saccadic eye movements was
      investigated in a dual-task paradigm that required a target-directed saccade in
      combination with a letter discrimination task. Subjects had to saccade to
      locations within horizontal letter strings left and right of a central fixation
      cross. The performance in discriminating between the symbols "E" and "E",
      presented tachistoscopically before the saccade within the surrounding
      distractors was taken as a measure of visual attention. The data show that visual
      discrimination is best when discrimination stimulus and saccade target refer to
      the same object; discrimination at neighboring items is close to chance level.
      Also, it is not possible, in spite of prior knowledge of discrimination target
      position, to direct attention to the discrimination target while saccading to a
      spatially close saccade target. The data strongly argue for an obligatory and
      selective coupling of saccade programming and visual attention to one common
      target object. The results favor a model in which a single attentional mechanism
      selects objects for perceptual processing and recognition, and also provides the
      information necessary for motor action.

PMID- 8759452
TI  - Neural encoding of binocular disparity: energy models, position shifts and phase
      shifts.
AB  - Neurophysiological data support two models for the disparity selectivity of
      binocular simple and complex cells in primary visual cortex. These involve
      binocular combinations of monocular receptive fields that are shifted in retinal
      position (the position-shift model) or in phase (the phase-shift model) between
      the two eyes. This article presents a formal description and analysis of a
      binocular energy model with these forms of disparity selectivity. We propose how
      one might measure the relative contributions of phase and position shifts in
      simple and complex cells. The analysis also reveals ambiguities in disparity
      encoding that are inherent in these model neurons, suggesting a need for a second
      stage of processing. We propose that linear pooling of the binocular responses
      across orientations and scales (spatial frequency) is capable of producing an
      unambiguous representation of disparity.

PMID- 8759453
TI  - Age-related functional field losses are not eccentricity dependent.
AB  - Previous studies have found an increase in peripheral target localization errors
      in normally sighted older adults. These results have been interpreted as
      indicative of a constriction of the "useful field of view". In the present study,
      we parametrically manipulated masking, distractors and stimulus luminance and
      examined the relationships between peripheral target localization and age. We
      found that backward masking and/or flashed distractors increased error rates.
      This decrement in performance was larger for more peripherally located targets
      and largest for the older subjects at all stimulus locations. Stimulus luminance
      (either 2 or 78 cd/m2) had no effect on peripheral localization performance at
      any age. We also demonstrated that all subjects, regardless of age, had higher
      localization error rates to more peripherally located targets. In older subjects,
      error rates increased equally at all eccentricities; that is, there was an
      eccentricity independent increase in the number of target localization errors as
      a function of age. This finding does not support the interpretation of a
      selective constriction of the functional visual field in older subjects.

PMID- 8759454
TI  - Lectin cytochemical analysis of glycoconjugates in photoreceptor cell membranes
      of Lampetra japonica.
AB  - Seven types of ferritinized lectin were used to examine the distribution of
      glycoconjugates on the outer segment membranes of lamprey photoreceptor cells.
      Ultrastructural pre-embedding labeling revealed that peanut agglutinin, soybean
      agglutinin and Ricinus communis agglutinin I were preferentially bound to the
      proximal, lateral and luminal surfaces of the long cell outer segments, whereas
      Griffonia simplicifolia agglutinin II and concanavalin A agglutinin were bound to
      the corresponding surfaces of the short cell outer segments. The results indicate
      that there is marked difference in the composition of glycoconjugates over the
      outer segment membranes between long and short photoreceptors.

PMID- 8759455
TI  - Proton inhibition of the NMDA-gated channel in isolated catfish cone horizontal
      cells.
AB  - The effect of H+ on the N-methyl-D-aspartate-induced (NMDA) membrane current in
      enzymatically isolated catfish cone horizontal cells was investigated.
      Extracellular acidification to pH 5.5 blocked nearly completely the NMDA-induced
      current and reduced desensitization. The pK for the H+ effect was 6.5, near that
      for the free amino acid histidine. Protons did not alter the receptor affinity
      for NMDA and the inhibition was insensitive to the membrane potential and surface
      charge screening. However, extracellular H+ increased the IC50 for Zn2+. These
      results indicate that protons can modulate the NMDA-induced membrane current by a
      mechanism that may include interaction with histidine residues.

PMID- 8759456
TI  - Matched filtering by a photoreceptor membrane.
AB  - This study demonstrates how phototransduction cascades and membranes tune
      photoreceptor response dynamics to image quality, and eliminate noise introduced
      in cell signalling. Intracellular recordings from intact retina confirm that the
      light-adapted photoreceptors of the crane fly Tipula paludosa (Diptera;
      Tipulidae) have a slow response, appropriate for their visual ecology. To provide
      a slow response, the phototransduction cascade's impulse response fails to narrow
      with light-adaptation, despite reductions in the timescales of latency and
      quantum bumps. The photoreceptor membrane acts as a passive RC-filter, because
      light induced depolarization inactivates voltage-gated potassium currents. The
      frequency response of the membrane equals the cascade's and, as a result, the
      membrane is a matched filter that suppresses photon shot noise. This type of
      broad-band filter, matched to the predictable dynamics of preceding processes to
      remove noise, could be widely employed in vision and in many other chains of
      cellular communication.

PMID- 8759457
TI  - A chromatic-cancellation property of human pupillary responses.
AB  - The pupil exhibits a response property somewhat analogous to perceptual red-green
      cancellation. Across a limited range of flash intensities near threshold,
      pupillary constrictions evoked by red flashes can be reduced, if not nulled, by
      the simultaneous addition of a green flash. The percentage of trials on which a
      stimulus-evoked response can be correctly discriminated from noise also falls to
      chance level as a green flash is added to the red flash. In terms of the quanta
      absorbed by L and M cones, the cancellation can be modelled as a function of
      magnitude of 0.65*L-M.

PMID- 8759458
TI  - Masking of the achromatic system: implications for saccadic suppression.
AB  - Brief (10 msec) increments, presented on a white adapting background, are known
      to elicit a spectral sensitivity function with a broad mid-spectral peak (King
      Smith & Carden, 1976). We have found that a luminance decrement, presented as
      either a forward or backward mask, dramatically alters the form of the resultant
      sensitivity function: the broad mid-spectral peak is replaced by a color-opponent
      function with narrow peaks at 520 and 620 nm. Over the region of the spectrum
      where this change in shape occurs, there is a substantial reduction in
      sensitivity. We also find that the mask is more effective when it precedes the
      stimulus than when it follows it, and that the masking can be characterized as a
      type A effect. The implications of these data for mechanisms of saccadic
      suppression are discussed.

PMID- 8759459
TI  - Binocular rivalry with isoluminant stimuli visible only via short-wavelength
      sensitive cones.
AB  - To test whether the binocular contour rivalry mechanism is tritanopic, we
      presented isoluminant, rival stimuli visible only via the short-wavelength
      sensitive (S) cones. We stimulated only the S cones with violet gratings
      superimposed on a bright yellow field that adapted the responses of the middle-
      and long-wavelength-sensitive (M and L) cones. We found that an S-cone grating
      presented to one eye rivalled with an orthogonal grating presented to the other.
      Rivalry persisted over a range of luminances and contrasts of the S-cone stimuli,
      and was greater than could be accounted for by nonrival fading. The spatial
      spread of rivalry from S-cone stimuli is similar to that for the same stimuli
      when visible also to the M and L cones (luminance stimuli). We found that an S
      cone stimulus would rival with a luminance stimulus, and exploited this to
      determine the equivalent luminance contrast of S-cone stimuli by putting them in
      a rivalry competition with luminance stimuli. For rivalry, the equivalent
      luminance contrast of isoluminant, S-cone stimuli is much less than their S-cone
      contrast. The existence of rivalry with isoluminant stimuli, along with earlier
      evidence that such stimuli can support stereopsis, challenges the view that an
      achromatic channel alone drives certain higher level functions such as depth
      perception.

PMID- 8759460
TI  - Flicker brightness enhancement and visual nonlinearity.
AB  - The purpose of this study was to investigate the nonlinear mechanism underlying
      brightness enhancement, in which a flickering stimulus appears brighter than a
      steady stimulus of equal mean luminance. The flickering and matching stimuli were
      temporally alternated. Both were cosine windowed to minimize the potential
      effects of temporal transients. Subjects adjusted the amplitude of the matching
      stimulus to match it in brightness to the flickering stimulus. The temporal
      frequency, modulation, and waveform of the flickering stimulus were varied. With
      sinusoidal flicker, brightness enhancement increased with increasing modulation
      at all frequencies, peaking at about 16 Hz at full modulation. The results were
      modeled by a broad temporal filter followed by a single accelerating
      nonlinearity. The derived temporal sensitivity of the early filter inferred from
      brightness enhancement decreased more slowly at high frequencies than the
      filter(s) inferred from flicker modulation thresholds. With low frequency
      sawtooth flicker, brightness enhancement was phase-dependent at low, but not at
      high modulations, suggesting that multiple neural mechanisms may also be involved
      in addition to an early nonlinearity.

PMID- 8759461
TI  - Two-dot alignment across the physiological blind spot.
AB  - Three competing hypotheses have been proposed for the cortical representation of
      the blind spot. These are: (i) the regions surrounding the blind spot maintain
      their spatial values; (ii) the opposite sides of the blind spot are represented
      adjacently at the cortex, so that the blind spot is "sewn-up"; and (iii) the
      blind spot is sewn-up with compensation occurring in the immediate surround of
      the blind spot, so that spatial values are distorted only in the immediate
      surround of the blind spot. To distinguish between these hypotheses we used a two
      dot alignment task, with the two dots straddling the blind spot at varying dot
      separations. Thresholds in the two-dot alignment task are limited by the cortical
      separation of the two dots. When thresholds for alignment across the blind spot
      are compared with thresholds over intact retina at the same eccentricity, the
      three hypotheses predict: (i) no change in thresholds; (ii) a lowering of
      thresholds; and (iii) a lowering of thresholds but only at separations slightly
      greater than the diameter of the blind spot. Thresholds across the blind spot
      were closely similar to thresholds across intact retina. The results do not
      support a sewing-up (with or without compensation) of the blind spot. Rather, our
      results are consistent with a preservation of spatial values around the blind
      spot.

PMID- 8759462
TI  - Increment threshold and purity discrimination spectral sensitivities of X
      chromosome-linked color-defective observers.
AB  - The goal of the study was to evaluate spectral opponency in nine X-chromosome
      linked color-defective observers. The tasks included increment threshold spectral
      sensitivity on an achromatic background, heterochromatic flicker photometry, and
      colorimetric purity discrimination. With a task of heterochromatic flicker
      photometry, the anomalous trichromatic observers showed spectral sensitivity of
      the corresponding dichromat. The increment threshold spectral sensitivity and
      colorimetric purity discrimination data were analyzed using the concept of
      standard cone photopigment spectral sensitivities for normal and defective
      vision, and a model that postulates one cone-additive and two cone-antagonistic
      systems. The model incorporated a shift of the peak spectral sensitivity of the
      long-wavelength-sensitive (LWS) pigment (for protan observers) or of the middle
      wavelength-sensitive (MWS) pigment (for deutan observers). Two dichromats and two
      anomalous trichromats did not show clear evidence of LWS vs MWS cone antagonism.
      Five anomalous trichromats showed such cone antagonism. Molecular genetic
      analysis of the opsin genes is presented for eight of the observers.

PMID- 8759464
TI  - Infants' sensitivity to uniform motion.
AB  - Uniform motion across the retina is a powerful cue to the perception of self
      motion. In spite of its importance for adaptive functioning, little is known
      about the early development of uniform motion sensitivity. Six-, 12-, and 18-week
      old infants viewed random-dot kinematograms depicting leftward or rightward
      uniform motion. The display induced optokinetic nystagmus (OKN), which a trained
      observer used to judge the direction of target motion. Both speed of motion and
      directional coherence were varied to obtain independent motion detection
      thresholds. Infants of all three ages could detect uniform motion, and their
      detection thresholds were constant during this period of development. This is in
      contrast to the clear improvements in relative motion sensitivity noted
      previously between 6 and 18 weeks of age with a preferential looking (PL)
      paradigm. The developmental differences between these studies may result from:
      (1) separate mechanisms for detecting uniform (absolute) and differential
      (relative) motion; or (2) separate mechanisms underlying OKN and PL response
      measures.

PMID- 8759463
TI  - The role of high-order phase correlations in texture processing.
AB  - Isodipole textures are pairs of texture ensembles whose autocorrelations, and
      hence power spectra, are equal. Examples of readily discriminable isodipole
      textures are well known. Such discriminations appear to require feature
      extraction, since the isodipole condition eliminates ensemble differences in
      spatial frequency content. We studied the effects of phase decorrelation on VEP
      indices of discrimination of isodipole texture pairs. Phase decorrelation, which
      ranged from 0.125 pi radians (slight randomization) to pi radians (complete
      randomization), was introduced in two ways: by independent jittering of each
      spatial Fourier component, and by a product method, which preserved correlations
      among certain quadruples of spatial Fourier components, despite pairwise
      decorrelation. For the even/random isodipole texture pair, independent phase
      decorrelation greater than 0.5 pi radians markedly reduced VEP indices of texture
      discrimination for all check sizes, and eliminated them entirely for check sizes
      of 8 min or greater. However, the product method preserved texture discrimination
      signals even with complete pairwise randomization of spatial phases. For the
      triangle/random isodipole texture pair, both kinds of phase decorrelation
      eliminated VEP indices of texture discrimination. These results imply that
      isodipole texture discrimination is based on fundamentally local processing, and
      not on global Fourier amplitudes-since the phase manipulations which eliminate
      texture discrimination preserve the Fourier amplitudes. The dependence of the
      antisymmetric response component (the odd harmonics) on phase decorrelation and
      texture type is consistent with a previously proposed model for feature
      extraction, and leads to constraints on how texture processing is modulated by
      contrast. The limited contribution of global spectral characteristics for small
      checks is consistent with a previously identified breakdown in scale-invariant
      processing.

PMID- 8759465
TI  - A comparison of sampling efficiency and internal noise level in young and old
      subjects.
AB  - Contrast detection in different levels of external visual noise allows a given
      loss in contrast sensitivity to be attributed to either an increase in the
      internal noise of the visual system, a decrease in sampling efficiency, or both.
      Sampling efficiency indicates how effectively the available stimulus information
      is utilized by the visual system. The aim of this study is to investigate the
      effect of normal ageing on sampling efficiency and internal noise. Contrast
      thresholds for sine-wave gratings of 6 c/deg were measured in the presence of
      four (including zero) levels of externally added visual noise in young and older
      healthy observers. Results showed that sampling efficiencies were significantly
      lower for the older group compared to the younger, while the internal noise
      showed no significant change. The implications of the data for the relative
      contribution of the optical and neural systems on visual function loss with
      ageing are discussed. Our results suggest that the neural system plays a major
      role in the loss of contrast sensitivity with ageing in normal, healthy eyes.

PMID- 8759466
TI  - Towards a texture naming system: identifying relevant dimensions of texture.
AB  - Recently, researchers have started using texture for data visualization. The
      rationale behind this is to exploit the sensitivity of the human visual system to
      texture in order to overcome the limitations inherent in the display of
      multidimensional data. A fundamental issue that must be addressed is what
      textural features are important in texture perception, and how they are used. We
      designed an experiment to help identify the relevant higher order features of
      texture perceived by humans. We used twenty subjects, who were asked to rate 56
      pictures from Brodatz's album on 12 nine-point Likert scales. Each subject was
      also asked to group these pictures into as many classes as desired. We applied
      the techniques of hierarchical cluster analysis and non-parametric
      multidimensional scaling (MDS) to the pooled similarity matrix generated from the
      subjects' groupings. We used Classification and Regression Tree Analysis (CART),
      discriminant analysis, and principal component analysis on the data from the
      scale ratings. The clusters generated from hierarchical cluster analysis remained
      intact in the MDS plots. We found that the MDS solutions fit the data well. The
      stress in the three-dimensional case is 0.12. The CART and discriminant analyses
      provided further justification for our interpretation. The three orthogonal
      dimensions we identified for texture are repetitive vs non-repetitive; high
      contrast and non-directional vs low-contrast and directional; granular, coarse
      and low-complexity vs non-granular, fine and high-complexity.

PMID- 8759467
TI  - Visual motion processing in one-month-old infants: preferential looking
      experiments.
AB  - The ability of infants to discriminate between opposite directions of motion was
      assessed using forced-choice preferential looking between a random-dot pattern
      which was segregated into regions which moved in opposite directions, and a
      uniform pattern in which all the dots moved in the same direction. The first
      experiment measured velocity thresholds (Vmin and Vmax) for direction
      discrimination; between 10 and 13 weeks Vmin decreased, while at the same time
      Vmax increased. The second experiment explored possible implications of this
      expanding velocity range for direction discrimination by younger infants. One
      month-olds showed no evidence for direction discrimination at any of a number of
      test velocities in the range 1-43 deg/sec. The 1-month-olds were also tested with
      two additional conditions: they could discriminate between moving and static
      patterns at velocities of 10 deg/sec or above, and they could also discriminate
      between coherent and incoherent motion at velocities of 21 deg/sec or below.
      Neither of these discriminations depends on sensitivity to the direction of the
      coherent motion. The results suggest that 1-month-olds may not be sensitive to
      the direction of visual motion.

PMID- 8759468
TI  - Visual motion processing in one-month-old infants: habituation experiments.
AB  - The ability of infants to discriminate between opposite directions of motion was
      examined in infant control habituation experiments. A group of 3-5-week-olds
      showed no evidence of discrimination between a random-dot pattern which was
      segregated into regions that moved in opposite directions, and a uniform pattern
      in which the dots all moved in the same direction. However, they did discriminate
      between segregated and uniform patterns in two additional conditions, neither of
      which required sensitivity to direction: in the first of these, segregation was
      based on the contrast between coherently moving and stationary dots, while in the
      second the contrast was between coherently and incoherently moving dots. Unlike
      the younger infants, a slightly older group of 6-8-week-olds proved capable of
      discriminating between the segregated and uniform patterns when the contrast was
      between opposite directions of motion. These results confirm and extend the
      results from preferential looking [Wattam-Bell, J. (1996). Motion processing in
      one-month-old infants: Preferential looking experiments. Vision Research, 36,
      1671-1677]; they suggest that direction discrimination may not emerge until
      around 6-8 weeks of age. The apparent lack of direction discrimination before 6
      weeks may reflect an inability to use directional cues to visually segment the
      segregated pattern, rather than an insensitivity to direction as such. To examine
      this, a further set of infants was tested for absolute direction discrimination
      i.e., between leftwards- and rightwards-moving uniform patterns. However, in this
      case neither 3-5- nor 6-8-week-olds showed any evidence of discrimination, which
      suggests that direction discrimination may first emerge for relative motion.
      Possible reasons for this are discussed.

PMID- 8759469
TI  - Contribution of chromatic mechanisms to the production of small-field optokinetic
      nystagmus (OKN) in normals and strabismics.
AB  - The contribution of chromatic mechanisms to motion processing is currently
      debated. Although OKN as a measure of motion processing has been employed for
      chromatic stimuli, the contribution of chromatic mechanisms to the production of
      OKN has not been assessed directly. We measured voluntary-pursuit and involuntary
      stare OKN responses to drifting patterns defined by colors modulated in a cone
      based color space which isolates luminance and color mechanisms. Results show
      that OKN responses are reduced for isoluminant stimuli, particularly for the
      stare conditions. The greatest reduction in responses occur for isoluminance
      stimuli that isolate the S cones. These results suggest that the chromatic
      mechanisms may have reduced input to the neural substrate that produces
      involuntary-stare OKN or that stare OKN has different temporal characteristics
      when stimulated by chromatic and luminance mechanisms. We also measured OKN
      asymmetries in several convergent strabismics in response to isoluminant and
      luminance patterns and compared their response to previous reports of horizontal
      OKN asymmetries in normal neonate infants. The results question the validity of
      either the modeling of OKN asymmetries in strabismus as incomplete development or
      the comparison of adult eye movement records evaluated with criteria for OKN with
      psychophysical forced choice evaluation of ocular drift in infants.

PMID- 8759470
TI  - Abnormalities of the retinal cone system in retinitis pigmentosa.
AB  - Patients with retinitis pigmentosa (RP) show delayed inner retinal responses as
      measured by the cone ERG response to a 30 Hz stimulus. To determine the extent to
      which this delay results from abnormalities of cone phototransduction, cone ERGs
      to single flashes were obtained from 21 patients with RP and a model of cone
      phototransduction was fitted to the leading edge of the a-waves of these ERGs.
      Nearly all patients showed an abnormally low sensitivity of cone
      phototransduction consistent with a reduction in the amplification of
      transduction. This abnormality can account for part of the delayed 30 Hz
      response. Analysis of post-receptoral potentials indicated that RP also slows the
      responses of the inner retina. A combination of these two factors, a sensitivity
      change at the receptor and a delay in the response of the inner retina, produces
      the delayed response of the cone flicker ERG in patients with RP.

PMID- 8759471
TI  - Guidelines for conducting tuberculin skin test surveys in high prevalence
      countries.

PMID- 8759472
TI  - Selection criteria for pulmonary rehabilitation.

PMID- 8759473
TI  - Influence of baseline airway calibre and pulmonary emphysema on bronchial
      responsiveness in patients with chronic obstructive pulmonary disease.
AB  - STUDY OBJECTIVE: Bronchial hyper-responsiveness (BHR) is widely observed in
      patients with chronic obstructive pulmonary disease (COPD). However, its clinical
      significance in COPD has not yet been established. To determine the factors that
      influence BHR in COPD, multiple linear regression analysis was used to analyse
      the relationship between BHR to methacholine and baseline forced expiratory
      volume in 1 s (FEV1), vital capacity (VC), residual volume (RV)/total lung
      capacity (TLC), static compliance (Cst), transfer coefficient of the lung (Kco),
      and the percentage of low attenuation area (%LAA) determined by computed
      tomographic (CT) scan. METHODS: Bronchial responsiveness to methacholine was
      determined in 63 patients with COPD by the dosimeter method and expressed as
      PD20FEV1. Residual volume and TLC were determined by body plethysmography. The
      percentage of low attenuation area was defined as the percentage of area less
      than -960 Hounsfield unit on a CT scan of the thorax. RESULTS: Forced expiratory
      volume in 1s (%predicted) and %LAA correlated with BHR (P = 0.023 and 0.020,
      respectively), while VC (%pred), RV/TLC, Cst and Kco did not. The coefficient of
      determination was 0.43. The regression analysis showed that a 10% increase in
      FEV1 (%pred) and a 10% decrease in %LAA would increase log(PD20FEV1) by 0.145 and
      0.117, respectively. CONCLUSIONS: A considerable proportion of the BHR in COPD is
      related to functional abnormalities and morphologic changes of emphysema, such as
      decreased baseline airway calibre and destruction of the lung parenchyma.

PMID- 8759474
TI  - Soluble interleukin-6 receptor levels in pleural effusions.
AB  - Generation of soluble cytokine receptors is a general phenomenon, and the roles
      of several such receptors have been investigated in clinical settings. Unlike
      other soluble cytokine receptors, soluble interleukin-6 receptor (sIL-6R) can act
      as an agonist and thus is implicated as an important modulator in the acute-phase
      reaction of prolonged inflammation. The purpose of the present study was to
      determine the roles of pleural sIL-6R in both differential diagnosis of pleural
      diseases and in the induction of acute-phase protein. Specific sandwich enzyme
      linked immunosorbent assays were used to determine sIL-6R and IL-6 in 19
      tuberculous, 48 malignant and 10 transudative effusions. Although IL-6 levels in
      pleural effusions were strikingly different, no significant differences in
      pleural sIL-6R levels were found between the groups. Pleural levels of IL-6 were
      invariably much higher, whereas those of SIL-6R were invariably lower than serum
      levels. Furthermore, IL-6, but not sIL-6R, levels in effusions correlated
      significantly with serum C-reactive protein levels. These results suggest that:
      (1) pleural levels of sIL-6R are not increased even in strong inflammation such
      as tuberculous pleurisy, nor significantly different among pleural diseases; and
      (2) the local levels of sIL-6R are not as important as expected for the induction
      of acute-phase proteins in patients with pleural diseases.

PMID- 8759475
TI  - Adenocarcinoma of the lung--clinical features and survival.
AB  - Four thousand patients were registered by the Edinburgh Lung Cancer Group in 1981
      1987; 9.5% had adenocarcinoma. Of these, 102 patients with pathological
      confirmation of the diagnosis, presenting to one hospital group in Edinburgh,
      were reviewed. Two cases were excluded after case note review. Of the remaining
      100, 64 were male and 36 were female, with a mean age of 73 years. The majority
      (89%) were smokers or ex-smokers, and 52% had a poor performance status
      (Karnofsky Index 10-70). Significantly, more adenocarcinoma patients underwent
      surgery compared to other cell types (39 vs. 19%, P < 0.01), and less were
      treated with radiotherapy (19 vs. 31%). The 5-yr survival rate for the
      adenocarcinoma patients was 19 vs. 7% in the remainder of patients. Of 39
      patients referred for surgery, 37 had lung resections and their 5-yr survival
      rate was 42%. Post-operative staging showed 48% in Stage I, 27% in Stage II and
      24% in Stage III. The majority of the long-term survivors had Stage I disease
      (64%). Forty-two percent of the patients received palliative therapy alone (all
      died within 10 months). Ten percent of patients receiving radiotherapy survived
      for 5 yr. Review of these cases suggested two patterns of presentations: (1)
      patients with poor performance status, extensive disease and often pleural
      involvement (16%); and (2) patients with more localized disease (39%), many of
      whom were suitable for surgical resection with surprisingly good prognosis.

PMID- 8759477
TI  - Spirometry in life-long non-smoking, healthy Chinese women in Taiwan.
AB  - To establish the spirometric values for normal, healthy Chinese women in Taiwan,
      the spirometry of 506 life-long non-smoking, healthy Chinese women was examined,
      including 140 subjects over the age of 60 years. Significant correlations among
      age, height and forced vital capacity (FVC), forced expiratory volume in 1 s
      (FEV1), FEV1/FVC%, peak expiratory flow (PEF), Vmax75, Vmax50, Vmax25 were found.
      However, there were no significant correlations between age and FEV1/FVC%, nor
      age and Vmax25 in the elderly group. FEV1 (FEV1*) and FVC (FVC*) were
      standardized to the overall mean height for elderly women using Cole's formula.
      The decline in FEV1* and FVC* with age were observed. The predicted value for the
      average 70-year-old woman with a height of 1.5 m derived from the present study
      is compared with those from other surveys of the elderly. The values from the
      present study are somewhat higher than the values from the Hong Kong study. The
      authors believe the fact that all of the present subjects were life-long non
      smokers might explain the differences.

PMID- 8759476
TI  - Effect of inhaled beclomethasone on serum markers of collagen metabolism in
      postmenopausal asthmatic women.
AB  - The use of inhaled corticosteroids in bronchial asthma has widened, but there is
      a lack of data on their effect on bone collagen synthesis and degradation. This
      paper reports the effect of three dose levels (200, 1000 and 2000 micrograms day
      1, 3 weeks each) of inhaled beclomethasone on specific characteristics of bone
      collagen metabolism in seven postmenopausal women with new asthma without any
      previous corticosteroid therapy. Serum aminoterminal (PINP) propeptide of human
      type I procollagen was seen, after an initial increase, to decrease significantly
      (from 42.2 to 35.5 micrograms l-1, P = 0.001) with the higher doses of inhaled
      beclomethasone, but no statistical change was found in the carboxyterminal
      propeptide (PICP) or type I collagen crosslinked telopeptide (ICTP). This data
      shows that type I collagen synthesis may be disturbed when using high-dose
      inhaled corticosteroids. However, further studies are needed to assess the
      effects of inhaled beclomethasone on the ability of the osteoblasts to form bone
      matrix, and on the density of bone during a longer treatment period with inhaled
      corticosteroids.

PMID- 8759478
TI  - Classification of pulmonary lesions into central and peripheral with a template
      applied on chest X-ray.
AB  - To facilitate the understanding of the anatomical localization of pulmonary
      lesions and to optimize diagnostic evaluation, a template was designed which, on
      conventional chest X-rays, could be employed to discriminate between central and
      peripheral pulmonary lesions. The term 'central' implies that the lesion should
      be visible in the tracheobronchial tree through a fibre-optic bronchoscope, and
      the term 'peripheral' suggests that the lesion is not visible through a
      bronchoscope. In 20 patients examined by fibre-optic bronchoscopy, the
      bronchoscope was wedged into four pre-selected segmental bronchi in each lung.
      Using fluoroscopy, the tip of the bronchoscope was marked out on the skin with
      leadshot. On subsequent chest X-rays, with posterior-anterior and right lateral
      views, the distances and angles of the markings of the bronchi were mapped out in
      relation to the main carina. These data were used to design the template.

PMID- 8759479
TI  - Totally implantable venous access devices in adult patients with cystic fibrosis.
AB  - Between September 1987 and April 1995, 33 totally implantable venous access
      devices (TIVADs) were implanted at the Cardiff Adult Cystic Fibrosis Centre,
      U.K., for the purpose of intermittent antibiotic therapy, including 22 PORT-A
      CATH (Simcare Ltd.) devices (PCs) to 18 patients, and 11 P.A.S.PORT (Simcare
      Ltd.) devices (PPs) to nine patients. There were 50 complications during 25 824
      days of catheter function which were severe enough to lead to removal of the
      devices in eight patients (six PCs and four PPs). Overall, patients' acceptance
      of these devices was excellent. Despite a shorter functional time and a higher
      rate of complications in PPs compared with PCs, PPs were preferred by many
      patients for cosmetic reasons. Totally implantable venous access devices provide
      safe, effective and convenient means of venous access in cystic fibrosis patients
      requiring intermittent antibiotic therapy.

PMID- 8759480
TI  - Outpatient management of chronic obstructive pulmonary disease.

PMID- 8759481
TI  - Cholesterol crystals in BAL fluid from patients with idiopathic pulmonary
      fibrosis.

PMID- 8759482
TI  - Bronchoalveolar lavage cytology in pulmonary fibrosis associated with
      neurofibromatosis.

PMID- 8759483
TI  - The performance of mini Wright peak flow meters after prolonged use.

PMID- 8759484
TI  - Bovine TB in badgers: a reappraisal of aetiology and pathogenesis.

PMID- 8759485
TI  - Do your clean or contaminate your bronchoscope.

PMID- 8759486
TI  - Nicotine and gastrointestinal disease.

PMID- 8759487
TI  - Cutaneous mosaicism.

PMID- 8759488
TI  - Smoking and cardiovascular disease.

PMID- 8759489
TI  - The spectrum of meningitis in a population with high prevalence of HIV disease.
AB  - We studied the spectrum of meningitis and impact of HIV infection retrospectively
      (8 months) and prospectively (4 months) in 284 adult patients with meningitis
      hospitalized in Soweto, South Africa. Tuberculous meningitis (TBM) was the most
      common cause of meningitis (25.4%) followed by acute bacterial meningitis (ABM;
      22.5%), acute viral meningitis (14.1%) and cryptococcal meningitis (13%). The in
      hospital mortality was > 40% in TBM, ABM, cryptococcal meningitis, the
      neurosurgery and the parameningeal/parenchymal groups. At least 37.3% of all
      patients were HIV-seropositive (only 67.9% of patients were tested). In at least
      27% of the study group the meningitis was an AIDS-defining illness (TBM,
      cryptococcal meningitis). Only 56.2% of patients with ABM had positive cultures
      (CSF or blood), of which Streptococcus pneumoniae was by far the most frequently
      found organism (35.8%). The spectrum of meningitis in HIV-affected communities in
      Africa can be expected to change towards a predominance of TBM and cryptococcal
      meningitis.

PMID- 8759490
TI  - CD4 and total lymphocyte counts as predictors of HIV disease progression.
AB  - CD4+ T-lymphocyte (CD4) counts are a standard laboratory marker of disease
      progression in HIV infection, but expense precludes their use in large parts of
      the world. Total lymphocyte counts (TLC), in contrast, are widely available. We
      compared CD4 and TLC counts as predictors of developing AIDS or death in 831 HIV
      positive out-patients (582 males and 249 females with both homosexual (males, n =
      316) and heterosexual (n = 515) transmission patterns. The first CD4 count <
      200/microliter and first TLC < 1250/microliter predicted similar (p = 0.52)
      survival, irrespective of clinical stage. For each clinical stage, a significant
      difference in progression to AIDS and mortality was predicted by TLC above or
      below 1250/microliter (p < 0.03). Survival and progression to AIDS occurred at
      similar rates in patients with a TLC < 1250/microliter or a CD4 count <
      200/microliter (p > 0.1), and patients with a TLC > 1250/microliter or a CD4
      count > 200/microliter (p > 0.5). A TLC < 1250/microliter preceded the
      development of Pneumocystis carinii pneumonia or cerebral toxoplasmosis in 76% of
      patients. In this longitudinal study, TLC and CD4 counts were equal predictors of
      disease progression. A TLC < 1250/microliter could be considered an indication
      for commencing cotrimoxazole prophylaxis.

PMID- 8759491
TI  - Duodenal mucosal ferritin in rheumatoid arthritis: implications for anaemia of
      chronic disease.
AB  - Anaemia is a common feature of rheumatoid arthritis (RA) and other chronic
      diseases. Among the alterations in iron metabolism contributing to this effect is
      a decrease in intestinal iron absorption. The mechanism for this is unknown, but
      might involve a 'mucosal block' process similar to that proposed in iron
      overload, whereby increased expression of an enterocyte storage protein binds
      absorbed iron and prevents its transfer to the circulation. We examined the
      effect of disease-modifying therapy on ferritin expression in duodenal mucosa in
      RA to determine whether it may play a role in the 'mucosal block' process.
      Endoscopic small bowel biopsies were obtained from 11 patients with active RA
      both before, and 6 months after, a course of either gold or methotrexate (MTX).
      Mucosal ferritin levels in small bowel and stomach were measured by radioimmune
      assay. Duodenal mucosal ferritin decreased significantly following treatment (p <
      0.05). There were no changes in gastric mucosal ferritin. The fall in duodenal
      mucosal ferritin correlated with indices of disease activity at start of therapy,
      and the largest decreases were in those patients showing the best response to
      treatment in terms of a fall in inflammatory markers. Site-specific changes in
      mucosal ferritin may underlie the altered iron absorption observed in active
      inflammatory disease by modifying the enterocyte 'mucosal block'.

PMID- 8759492
TI  - The systemic inflammatory response syndrome as a predictor of bacteraemia and
      outcome from sepsis.
AB  - Criteria defining the systemic inflammatory response syndrome (SIRS) were used to
      assess prospectively 270 clinical episodes in which blood cultures were taken
      from patients in general medicine. SIRS, severe sepsis and septic shock occurred
      in 149 (55%), 13 (5%) and 9 (3%) episodes, respectively. However, evidence of
      organ hypoperfusion indicating severe sepsis was recorded as sought in only 26%
      of episodes of SIRS. Crude mortality at 28 days increased sequentially as more
      SIRS criteria were met, rising from 12% in non-SIRS blood culture episodes, to
      36% when all four criteria were met. Mortality from severe sepsis and septic
      shock was 38% and 56%, respectively. In 61/64 (95%) episodes of clinically
      important bacteraemia, patients fulfilled SIRS criteria when the blood culture
      was taken. However, the positive predictive value of SIRS for predicting
      bacteraemia was only 7%. Patients who did not fulfil SIRS criteria when blood
      cultures were taken were at low risk of bacteraemia and comprised 45% (121/270)
      of the study population. Three patients in this low-risk group had bacteraemia.
      Mortality in bacteraemic patients with severe sepsis or septic shock who were
      initially treated with ineffective antibiotics for up to 48 h was 80%, compared
      to 42% in those always treated appropriately.

PMID- 8759494
TI  - Risk factors for infection in Malaysian patients with systemic lupus
      erythematosus.
AB  - To determine the incidence, types and risk factors for infection in systemic
      lupus erythematosus (SLE) patients in Kuala Lumpur, Malaysia, we retrospectively
      reviewed the medical records of 102 patients with definite SLE attending a
      specialist clinic. Details of major infections (pneumonia or severe infection
      requiring intravenous therapy) and minor infections, and their time of onset in
      relation to immunosuppressive therapy and disease flares were recorded. There
      were 77 major and 163 minor infections during 564 patient-years of follow-up. In
      the month following a course of pulse methylprednisolone, the incidence of major
      infection was 20 times higher and the incidence of minor infection was 10 times
      higher than at other periods (p < 0.0001). In the month after disease flare, the
      incidence of major infection was 10 times higher and the incidence of minor
      infection six times higher than at other times (p < 0.0001). After allowing for
      methylprednisolone therapy and disease flares, there was no increase in the rate
      of infections during treatment with azathioprine, oral or intravenous
      cyclophosphamide. There was no effect of renal involvement on infection rate.

PMID- 8759493
TI  - The emerging syndrome of envenoming by the New Guinea small-eyed snake
      Micropechis ikaheka.
AB  - The New Guinea small-eyed or ikaheka snake, Micropechis ikaheka, which occurs
      throughout New Guinea and some adjacent islands, is feared by the indigenes. The
      first proven human fatality was in the 1950s and this species has since been
      implicated in many other cases of severe and fatal envenoming. Reliable
      attribution of envenoming to this species in victims unable to capture or kill
      the snake recently became possible by the use of enzyme immunoassay. Eleven cases
      of proven envenoming by M. ikaheka, with two fatalities, were identified in Papua
      New Guinea and Irian Jaya. Five patients showed no clinical signs of envenoming.
      The other six patients showed symptoms typical of envenoming by other
      Australasian elapids: mild local swelling, local lymphadenopathy, neurotoxicity,
      generalized myalgia, spontaneous systemic bleeding, incoagulable blood and
      passage of dark urine (haemoglobinuria or myoglobinuria). Two patients developed
      hypotension and two died of respiratory paralysis 19 and 38 h after being bitten.
      In vitro studies indicate that the venom is rich in phospholipase A2, is
      indirectly haemolytic, anticoagulant and inhibits platelets, but is not
      procoagulant or fibrinolytic. It shows predominantly post-synaptic neurotoxic and
      myotoxic activity. Anecdotally, Commonwealth Serum Laboratories' (CSL) death
      adder antivenom has proved ineffective whereas CSL polyvalent antivenom may be
      beneficial. Anticholinesterase drugs might prove effective in improving
      neuromuscular transmission and should be tested in patients with neurotoxic
      envenoming.

PMID- 8759495
TI  - Imaging secondary neuroendocrine tumours of the liver: comparison of I123
      metaiodobenzylguanidine (MIBG) and In111-labelled octreotide (Octreoscan).
AB  - Functional imaging of neuroendocrine tumours with Octreoscan and I123
      metaiodobenzylguanidine (MIBG) is important for assessment prior to various
      therapies and assessing response. The two imaging methods have not been directly
      compared in hepatic neuroendocrine tumours. Patients (n = 18) were studied with
      both imaging techniques. The sensitivity of Octreoscan was 94%, and that of MIBG
      39%. No previously occult primary sites were detected. Concurrent octreotide
      therapy did not reduce the sensitivity of Octreoscan. Widespread bone metastases
      were seen in two post-liver-transplant patients using Octreoscan. Octreoscan is a
      sensitive means of detecting hepatic neuroendocrine tumours, and the more
      specific technique. MIBG has poor sensitivity, reducing its clinical utility.
      Therapy with I131-MIBG is likely to be applicable to relatively few patients.

PMID- 8759496
TI  - Psychiatric aspects of Cushing's syndrome.
AB  - Patients with Cushing's syndrome were studied (n = 209, 78% females). Control
      patients had pituitary adenomas secreting growth hormone or prolactin. Age at
      diagnosis of Cushing's syndrome was 8-74 (mean 39) years. Duration of symptoms
      was 0.2-9 (median 2.0) years. Adverse life events within the 2 years preceding
      the onset of Cushing's syndrome were not significantly commoner than in controls.
      Depressive illnesses were associated with the presence of adverse life events (p
      < 0.001). Depressive illness was more common in females (p < 0.01). There were no
      significant differences in the severity of depression in the different types of
      Cushing's syndrome. Pathological anxiety had been diagnosed in 26 patients (12%),
      mania or hypomania in six patients (3%) and confusion in three patients (1%).
      Psychotic illness had been diagnosed in 16 patients (8%) and was more common in
      adrenal carcinomas (p < 0.01). Significant psychiatric illness, usually
      depressive, preceded the onset of all symptoms and signs of Cushing's syndrome in
      25 patients (12%); 23 of these developed pituitary Cushing's disease, and two
      adrenal adenomas. When Cushing's syndrome was diagnosed, significant psychiatric
      illness, usually depression, was present or had been a feature of Cushing's
      syndrome in 120 (57%) patients.

PMID- 8759497
TI  - Treatment of Wilson's disease: the historical background.

PMID- 8759499
TI  - Public concern about meningitis.

PMID- 8759498
TI  - Maintenance doses of warfarin in Chinese patients.

PMID- 8759500
TI  - A non-compliant smoker with brittle asthma.

PMID- 8759501
TI  - The meningitis scare in perspective.

PMID- 8759502
TI  - Minimising the risk of travel infection.

PMID- 8759503
TI  - A GP guide to tropical skin infections.

PMID- 8759504
TI  - Is MRSA a risk in the community?

PMID- 8759505
TI  - Grommets: what GPs need to know.

PMID- 8759506
TI  - When to use antihypertensives.

PMID- 8759507
TI  - A fiancee seeking genetic advice.

PMID- 8759508
TI  - Cholesterol: a rational approach.

PMID- 8759509
TI  - The technology of pacing decoded.

PMID- 8759511
TI  - The challenge of unstable angina.

PMID- 8759510
TI  - Cardiovascular testing: a GP guide.

PMID- 8759512
TI  - Managing patients after an MI.

PMID- 8759513
TI  - Overcoming culture and language barriers.

PMID- 8759514
TI  - Development and ageing of the RPE in a marsupial, the quokka.
AB  - We have previously shown that the mature adult quokka, aged between 8 and 15
      years, has a distinct cell topography in the retinal pigment epithelium (RPE). We
      reported that the adult cell densities were high in central temporal retina and
      low in a peripheral band, adjacent to the ora serrata, a region with a
      concentration of multinucleate cells. In the present paper, we have studied the
      development of these features in order to understand how they mature, as well as
      to gain insight into regional specializations of the RPE. Retinal area, cell
      density and the extent of multinucleation were analysed using whole-mounted
      retinae from animals aged post-natal day (P) 2 to 15. The retina continues to
      grow in area throughout life, however, RPE cell number does not change. The
      features of the mature adult RPE develop at different times over the entire
      lifespan of the animal. In peripheral retina, cell density decreases throughout
      life and the band of low cell density becomes progressively wider and more
      distinct with age with an increasing proportion of multinucleate cells. By
      contrast, RPE cell density in equatorial retina remains, throughout life, at the
      level observed in 1-year-old animals. A specialization of high cell density in
      temporal central RPE was discernible in animals older than 2 years, with the cell
      density of this region increasing steadily beyond this age. Central regions of
      other quadrants demonstrate a constant and relatively uniform density with age.
      The RPE in the marsupial quokka is a dynamic tissue, demonstrating topographic
      changes throughout life.

PMID- 8759515
TI  - Macrophage subpopulations and RPE elimination in the pathogenesis of experimental
      autoimmune pigment epithelial protein-induced uveitis (EAPU).
AB  - Experimental autoimmune pigment epithelial protein-induced uveitis (EAPU) is a
      new type of disease that destroys the retinal pigment epithelium (RPE), and
      exhibits a hitherto unknown form of progressive chorioretinal dystrophy in which
      neuroretinal inflammatory foci are absent. The present study was aimed at
      studying the expression of adhesion molecules, and the kinetics of the appearance
      of the main types of macrophages and other intraocular immunocompetent cell
      populations in the various stages of this disease. EAPU was evoked in Lewis rats
      by immunization with the membrane protein from bovine RPE cells containing PEP-65
      as main constituent. In the uvea, increased expression of intercellular adhesion
      molecule-1, of class II major histocompatibility complex antigen, and of ED2
      macrophage reactivity were observed closely before the onset of EAPU. Expression
      of these reactivities was also slightly elevated by injections of the applied
      adjuvants alone. The onset of EAPU was mainly characterized by initial uveal
      infiltrations of ED1+ macrophages and a minor population of CD4 T cells, and an
      increase in ED3, ED7 and perivascular ED2 reactive macrophages. This was followed
      by the development of focal accumulations of ED1+ cells at both sides of the
      Bruch's membrane-RPE layer (Dalen-Fuchs nodules) which was permeated and
      disintegrated at these sites. The outer choroidal layer, the anterior iridal
      surface, and the base of the ciliary body more frequently contained active
      inflammatory cells than the other uveal areas. Lymphoid cells were found
      scattered through the uvea, aqueous and vitreous. The sites of increased activity
      of ED2+ and ED3+ cells in the uvea were rather similar to those of ED1
      macrophages in the various stages of EAPU. Starting from multiple foci, the
      process of the formation of plaque-shaped cell accumulations in severe EAPU
      progressed along the RPE and exhibited a chronic character. The results of this
      study show that ED1+, ED2+, ED3+ and ED7+ subpopulations of macrophages are
      actively involved in an immunopathological process in which the RPE is the
      target. The thickening of the plaque-shaped cell accumulations stops if the
      integrity of all RPE cells at that site has been affected. We postulate that this
      is the result of antigen elimination while additional influence of the abrogation
      of RPE cytokine production is presumed.

PMID- 8759516
TI  - Matrix metalloproteinases and their inhibitors in aqueous humor.
AB  - Matrix metalloproteinase activity is the rate-limiting step in extracellular
      matrix degradation. One mechanism by which metalloproteinases are regulated is
      through the activity of their endogenous inhibitors, the tissue inhibitors of
      metalloproteinases. Since metalloproteinase activity is a key component of the
      angiogenic process and many anterior segment structures are largely avascular, we
      became interested in examining aqueous humor for the presence of
      metalloproteinases and their endogenous inhibitors. Using zymography, we have
      identified the presence of several metalloproteinases in normal aqueous humor.
      Treatment with 4-aminophenylmercuric acetate, an organomercurial which activates
      latent metalloproteinases, revealed that all metalloproteinases were in their
      active state. By Western blot analysis, normal aqueous humor was also found to
      contain at least two tissue inhibitors of metalloproteinases. Subsequent partial
      purification by two successive chromatographic steps revealed the presence of
      inhibitory activity against collagenase, endothelial cell DNA synthesis, and
      angiogenesis on the chick chorioallantoic membrane. The presence of
      metalloproteinases and their inhibitors in normal aqueous humor, a fluid which
      bathes avascular ocular structures, suggests that future studies should examine
      whether an imbalance in this protease/inhibitor family may contribute to the
      anterior chamber extracellular matrix alterations associated with diseases such
      as ocular neovascularization and glaucoma.

PMID- 8759517
TI  - Identification of prostanoid receptors in rabbit non-pigmented ciliary epithelial
      cells.
AB  - Preliminary ligand binding studies demonstrated that the membrane preparations of
      the rabbit nonpigmented ciliary epithelial cell line have 3H-prostaglandin E2
      binding sites. The binding sites were specific for 3H-prostaglandin E2 as
      demonstrated by competition with unlabeled prostaglandin E2. The IC50 of
      prostaglandin E2 for the inhibition of 3H-prostaglandin E2 binding was 435 nM.
      The stimulation of adenylyl cyclase and phospholipase C by prostanoid receptor
      agonists, in rabbit non-pigmented ciliary epithelial cells resulted in the
      formation of either cyclic AMP or inositol phosphates. Prostaglandin E2 and 16-16
      dimethyl prostaglandin E2 (both are EP1, EP2, EP3 and EP4 receptor agonists). 11
      deoxy prostaglandin E1 (EP2, EP3 and EP4 receptor agonist), butaprost (EP2
      receptor agonist), and prostaglandin D2 (DP receptor agonist) stimulated the
      formation of cyclic AMP in a dose-dependent manner. Maximal stimulation occurred
      between 1.25 and 2.5 microM for prostaglandin E2 and 16,16-dimethyl prostaglandin
      E2 and between 10 and 20 microM for 11-deoxy prostaglandin E1 and prostaglandin
      D2. Prostaglandin E2 and 16,16-dimethyl prostaglandin E2 were more potent (EC50
      of 0.25 microM and 0.42 microM respectively) than 11-deoxy prostaglandin E1,
      butaprost or prostaglandin D2. The formation of cyclic AMP by prostaglandin D2
      was inhibited by BW868C, a highly selective DP receptor antagonist. 17-phenyl
      trinor prostaglandin E2, prostaglandin F2 alpha and U46619, the EP1, FP and TP
      receptor agonists, respectively stimulated phospholipase C (as measured by the
      formation of total inositol phosphates) in a dose-dependent manner. The agonists
      11-deoxy prostaglandin E1 and butaprost coupled to adenylyl cyclase via guanine
      nucleotide binding protein, G8, did not increase the turnover of inositol
      phosphates. The results of the present study suggest that rabbit non-pigmented
      ciliary epithelial cells express EP1, EP2, DP, FP and TP receptors.

PMID- 8759518
TI  - Differential phosphorylation of alpha-A crystallin in human lens of different
      age.
AB  - Previous studies have demonstrated that a major site of in vivo phosphorylation
      of alpha-A crystallin from human lens is serine-122. To determine the relative
      degree of this phosphorylation in alpha-A crystallin from human lenses of
      different age, alpha-A crystallin was purified from total lens proteins, followed
      by sequential digestion with lys-C and asp-N endoproteases. Mass spectral
      analysis of the asp-N peptide fragments that contained serine-122 demonstrated
      undetectable levels of phosphorylation from infant human lenses (41 days, 2
      months and 4 months of age). Identical analysis of alpha-A crystallin from older
      lenses (12, 15, 40 and 73 years of age) indicated significant phosphorylation of
      serine-122, demonstrating that phosphorylation of the serine-122 residue of alpha
      A crystallin does not occur during the aging process, but is rather a
      developmentally regulated event in the human lens.

PMID- 8759519
TI  - Inhibition of cataracts in moderately diabetic rats by aminoguanidine.
AB  - The effect of aminoguanidine (AG), an inhibitor of advanced glycation, on the
      development of cataracts was studied in diabetic rats. Rats were made diabetic
      with streptozotocin, and based on the level of plasma glucose they were grouped
      as moderately (< 350 mg dl-1 plasma glucose) and severely (> 350 mg dl-1 plasma
      glucose) diabetic. One half of the animals in each group received AG (25 mg kg-1
      body weight each day), intraperitoneally, starting from the day of streptozotocin
      injection. Progression of lens opacification was recorded using Fundus and
      Scheimpflug photography at regular time intervals. On the ninetieth day all the
      rats were killed and the levels of advanced glycation end products (AGE) was
      determined by measuring the non-tryptophan fluorescence of the lens soluble and
      insoluble fractions. Densitometric analysis of Scheimpflug images showed that in
      diabetic rats lens opacification progressed in a biphasic manner, an initial slow
      progression for the first 60 days, followed by a steep increase during next 30
      days. Moderately and severely diabetic rats developed lens opacities more or less
      at the same time. AGE fluorescence in the lens soluble fractions increased three
      fold and seven-fold in the moderately and severely diabetic rats, respectively;
      whereas in insoluble fractions there was a 30% and three-fold increase in the
      moderately and severely diabetic rats, respectively. Although AG treatment
      inhibited the AGE fluorescence of lens soluble and insoluble fractions by about
      56% and 75% in moderately diabetic and by 19% and 52% severely diabetic rats,
      respectively, the development of cataracts was delayed only in the moderately
      diabetic rats. These results thus suggest that the effect of AG is indeed
      inhibition of the formation of AGEs. However, in the severely diabetic rats the
      beneficial effect of AG is overwhelmed by the excessive accumulation of AGEs.

PMID- 8759520
TI  - Effect of histamine on phosphoinositide turnover and intracellular calcium in
      human ciliary muscle cells.
AB  - This report describes the effect of histamine on phospholipase C (PLC) activity
      and calcium mobilization in cultured human ciliary muscle cells. PLC activity was
      assessed by measuring the production of inositol phosphates and intracellular
      calcium mobilization was assessed by Fura 2 ratio fluorometry. The stimulation of
      PLC by histamine was concentration dependent with an EC50 of 0.96 microM. The H1
      antagonist chlorpheniramine blocked the response with an IC50 of 0.53 microM.
      Calcium fluorometry experiments indicated a mean basal calcium concentration of
      36 nM with a 10(-4) M histamine induced mean peak value of 1132 nM followed by a
      gradually declining plateau phase. EC50 and IC50 (chlorpheniramine) values from
      histamine induced peak calcium concentrations agreed with the PLC results.
      Pretreatment of the cells with the PLC inhibitor U73122 at 10(-6) M completely
      blocked histamine induced calcium mobilization. Removal of extracellular calcium
      eliminated the plateau phase but not the initial calcium peak indicating that
      both intra and extracellular calcium sources are required for a normal response.
      The calcium ATPase inhibitor thapsigargin caused depletion of intracellular
      calcium stores and prevented a subsequent normal calcium mobilization response to
      histamine. Ryanodine, a release inhibitor of certain intracellular calcium
      stores, had no effect on the histamine induced response. The results of these
      experiments indicate that histamine, via an H1 receptor, activated the PLC second
      messenger pathway, and caused a multi-phasic mobilization of both intracellular
      and extracellular calcium. The entry of the extracellular calcium was shown to be
      dependent upon release of calcium from a ryanodine insensitive intracellular
      store.

PMID- 8759521
TI  - Variation in cellular glutathione peroxidase activity in lens epithelial cells,
      transgenics and knockouts does not significantly change the response to H2O2
      stress.
AB  - This investigation examines the contribution of glutathione peroxidase (GSHPx-1)
      in degrading H2O2 in lens preparations. Rabbit (N/N1003A) and normal and GSHPx-1
      transfected mouse (alpha TN4-1) lens epithelial cell lines and normal and GSHPx-1
      transgenic and knockout mouse lenses were utilized. GSHPx-1 activity in the cell
      lines was increased from two-fold to about four-fold, in the lenses from
      transgenics more than four-fold and the lenses from knockouts had less than 3% of
      normal GSHPx-1 activity. The transgenic and knockout mice as well as their lenses
      appeared normal for up to 3 to 4 months, the longest period of observation. The
      preparations were subjected to oxidative stress by placing them either in a
      medium containing 120 or 300 microM H2O2 or utilizing photochemical stress where
      the H2O2 levels normally rise to about 100 microM over a few hours in the
      presence of a normal lens. With all preparations, it was found that either
      markedly increasing or eliminating GSHPx-1 activity had only a small effect on
      the system's ability to metabolize H2O2, 1,3-bis(2-chloroethyl)-1-nitrosourea
      (BCNU), an inhibitor of GSSG reductase (GSSG Red) and 3-aminotriazole (3-AT), an
      inhibitor of catalase, also had little effect. However, the addition of both
      inhibitors caused a marked decrease in H2O2 degradation. Examination of the
      distribution of GSHPx-1 in the lens indicated that the activity per milligram of
      protein was evenly distributed between the epithelium and the remainder of the
      lens in the normal lens and was about 1.7-fold greater in the epithelium of
      transgenic lenses than in the remainder of the lens. Surprisingly, the
      distribution of GSSG Red was quite different with eight- to ten-fold more
      activity in the epithelium. Catalase was also found to be concentrated in the
      epithelium. With H2O2 exposure, a rapid loss of non-protein thiol (NP-thiol) was
      found in cell cultures and in the epithelia of cultured lenses. However, the
      remainder of the lens showed little change in NP-thiol. The variation of GSHPx-1
      activity did not influence the NP-thiol changes which occurred more rapidly and
      to a greater extent in the presence of BCNU. The addition of BCNU also caused a
      decrease in total lens NP-thiol. Examination of thymidine incorporation and
      choline transport, indicators of nuclear and membrane function, also reflects the
      H2O2 degradation data, showing little difference in the degree to which H2O2
      effects these parameters in lenses from normal and transgenic animals. Catalase
      activity is four- to six-fold greater than GSHPX-1 activity in the alpha TN4-1
      cell lines, about three-fold lower in the rabbit cell line and, remarkably, about
      18-fold lower than the peroxidase in the normal mouse lens. In spite of such
      observations, the consistent overall conclusion is that GSHPx-1 and catalase
      function together but when GSHPx-1 is knocked out or GSSG Red is inhibited,
      catalase is able to protect the system from H2O2 stress. Indeed, the young mouse
      does not appear to require GSH Px-1 for normal function.

PMID- 8759522
TI  - Organ culture of human main and accessory lacrimal glands and their secretory
      behaviour.
AB  - The purpose of this study was to investigate the in vitro viability and secretory
      behaviour of human main and accessory lacrimal glands using an organ culture
      technique. We evaluated the influence of the second messengers cAMP and cGMP on
      secretion. Fragments less than 1 mm3 of main and accessory lacrimal glands as
      well as conjunctiva were cultured for 2-72 hr at 37 degrees C in an atmosphere
      consisting of 50% O2, 45% N2 and 5% CO2, using a specially devised culture medium
      (+/- cAMP or cGMP). The conjunctival tissue served as negative control.
      Supernatants were assayed for secretory-component-bound IgA, lactoferrin and
      lysozyme using ELISA. Cultured tissue pieces were embedded in paraffin, serially
      sectioned, stained and their volumes calculated using an image-analysis system.
      This enabled us to differentiate between secretory, connective and fatty tissue.
      Secreted exudate was correlated to the volume of secretory tissue. Viability of
      cultured organ pieces was determined by electron microscopic examination.
      Suitable organ culture conditions for human lacrimal glands were successfully
      established. Electron microscopic examinations proved that the structural
      characteristics of the organ and the polarity of the individual cells were well
      preserved up to 22 days of culture. Culture supernatants were assayed for
      secretory-component-bound IgA, lactoferrin, and lysozyme and showed that the
      amount of protein secreted increased with time. Upon addition of cAMP (1 x 10(-3)
      M) and cGMP (4 x 10(-3) M), secretion was elevated in both main and accessory
      lacrimal glands. An organ culture system for lacrimal glands was developed that
      maintains their structural and cellular characteristics as well as their
      secretory function for up to 22 days. We believe that this system mimics the in
      vitro state of the organ better than monolayer cultures and thus proves to be a
      valuable tool when examining lacrimal function in vitro. The fact that both cAMP
      and cGMP enhance secretion may help to shed some light on the cellular pathways
      human main and accessory lacrimal glands use for signal transduction.

PMID- 8759523
TI  - A simple organ culture model for assessing the effects of growth factors on
      corneal re-epithelialization.
AB  - The effects of growth factors on re-epithelialization of wounded human and bovine
      corneas were studied in a simple organ culture system. Excisional trephine and
      epithelial scrape wounds were created on bovine and human corneo-scleral rings in
      which the endothelial corneal concavity was then filled with an agar-collagen
      mixture. Organ culture was undertaken at 37 degrees C in a humidified 5% CO2
      incubator with serum-free Medium 199 maintained at the level of the conjunctival
      epithelium. Rates of reepithelialization in response to addition of exogenous
      epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and
      transforming growth factor type beta 1 (TGF-beta 1) were assessed by image
      analysis. Corneal cultures could be maintained for up to 3 weeks without
      significant stromal oedema or keratocyte deterioration and with little loss of
      epithelial architecture. Following wounding the cornea reepithelialized in a
      similar fashion to that observed in vivo i.e. a lag phase followed by
      migration/proliferation and the reformation of an intact multilayered epithelium.
      EGF accelerated, basic FGF had no effect on, and TGF-beta 1 inhibited the rate of
      corneal re-epithelialization. Our organ culture model maintains corneal integrity
      and provides a practical system in which to study factors that modulate corneal
      reepithelialization following wounding.

PMID- 8759524
TI  - Hydrodynamics of ageing Bruch's membrane: implications for macular disease.
AB  - The hydrodynamic properties of isolated human Bruch's membrane and choroid were
      investigated as a function of age and retinal location. Macular and peripheral
      regions of the fundus showed an exponential decline of hydraulic conductivity
      with half-lives of 15 and 22 years respectively. Comparison of age profiles for
      hydraulic conductivity and lipid deposits suggests the involvement of two
      discrete processes for reduction in transport capability. The first appears to
      involve 'membrane remodelling' with a programmed decay rate leading to a major
      reduction in hydraulic conductivity by the fifth decade of life. The second
      commences in the fourth decade and is apparently dependent on the lipid content
      of Bruch's membrane.

PMID- 8759525
TI  - Light intensity distributions in refracting structures placed between crossed
      polarizers.
AB  - A number of refracting structures each with different optical properties, were
      placed between crossed polarizers, illuminated with diffuse light and
      photographed. The images of the characteristic cross pattern (isogyres) seen in
      such structures, viewed under these conditions, were analysed to determine the
      relative distributions of light intensity within the patterns. The experimental
      findings show that intensity distributions are related to the optical properties
      of a refracting structure. Comparison of dimensional differences shows that in a
      larger sample the profile of light intensity distribution (in the quadrants
      between the isogyres) is more symmetrical and the peak is closer to the centre of
      the quadrant. Sharper peaks are seen in the intensity distribution profiles of
      gradient-index structures than in profiles of homogenous-index bodies of
      comparable dimensions. Some agreement was found between an experimental
      observation and a previously derived mathematical model for homogenous index,
      curved bodies.

PMID- 8759527
TI  - Incorporating immunological ideas in epidemiological models.
AB  - Many diseases show important interactions between epidemiology and immunology.
      Both models and data suggest that epidemiologically controlled variables, like
      frequency and intensity of exposure, can affect immunological outcomes in a wide
      variety of diseases. Conversely, the results of the immunological "battle"
      between host and parasite determine the ability of the parasite to spread. I
      present a simple model with two possible states of infection, which assumes that
      higher exposure to infection is correlated with likelihood of acquiring a more
      severe infection. For some parameter values, this model leads to simultaneous
      stability of the disease-free equilibrium and an endemic equilibrium, implying
      that the disease might be able to persist in a population that it could not
      invade. I also derive a simple and interpretable sufficient condition for
      multiple stable states. The "cartoon" model presented here shows that interaction
      between epidemiology and immunology can have important effects on the invasion
      and persistence of diseases. In particular, it raises the possibility that this
      mechanism can lead to mathematical "catastrophe" and to long-term cycles in
      disease prevalence.

PMID- 8759526
TI  - Simultaneous induction of cytokine mRNA expression in the anterior uvea during
      endotoxin-induced uveitis in the rat.

PMID- 8759528
TI  - Sexual selection enhances population extinction in a changing environment.
AB  - Animal communication systems (sexual and social communications) may cause an
      extra selection load on populations because of the cost of the signals. Under
      environmental deterioration, the cost of signaling must increase, resulting in an
      evolutionary reduction in the signal if it is maintained by natural selection vs.
      sexual selection balance. And in turn, the degeneration of the signal tends to
      reduce the selection load imposed by the cost. But if female preference resides
      in a population, sexual selection may prevent rapid degeneration of the signal,
      which is increasingly costly. Hence sexual selection may enhance populational
      extinction by increasing selection load under environmental changes. This paper
      evaluates the extra selection load that a communication system suffers when an
      environment deteriorates or the ecological optimum for a signal changes in the
      opposite direction to the sexual selection optimum.

PMID- 8759529
TI  - Aspects of bioenergetics and civilization.
AB  - By means of an allometric relation between the oxygen consumption rate and the
      body mass of an animal a metabolic coefficient is derived that can be used as a
      measure of standard metabolism in different animal species. This coefficient
      increased in the course of evolution corresponding to the time of appearance of
      each class of animal. It reached its highest values in Primates and passerine
      birds. A further increase across an energetic threshold was only possible with
      human civilization. A similar approach to evolution is performed through an
      encephalization coefficient showing that in all phases of evolution, species
      existed with a much larger relative brain volume than the other members of their
      class. These species might have established a non-human civilization on Earth if
      evolution would have taken another path. Finally, social activities of insects
      and the use of external energy sources by animals are discussed to show further
      implications of this bioenergetic approach to evolution.

PMID- 8759530
TI  - State-space analysis of a myocybernetic model of the lower urinary tract.
AB  - To study the control of the lower urinary tract, the state space of the
      myocybernetic model by Bastiaanssen et al. (1996) is analysed. This model is able
      to respond to input signals from a neural network and includes descriptions of
      the muscle dynamics of both the detrusor in the bladder wall and the urethral
      sphincter. The equilibrium states of the model for constant input signals were
      found by evaluation of the roots of calculated flow curves. Two types of
      equilibrium states could be distinguished: (i) the inflow and the outflow of the
      bladder are both equal to zero and (ii) the bladder in- and outflow are both
      equal to a prescribed small constant flow from the ureters into the bladder. The
      first type of equilibrium features a very high bladder pressure, which in vivo
      could result in a reflux of urine into the ureters. The second type shows a
      constant loss of urine. For different combinations of constant input signals,
      several stable equilibrium states of both types were found. The neural controller
      should avoid these states so that the lower urinary tract fulfils either its
      storage or its voiding function. Therefore, the trajectory through the state
      space of a simulated normal filling and micturition event was evaluated here. It
      appeared that equilibrium states were avoided by rapid changes of the input
      signals. The behaviour of the model outside the normal trajectory is compared
      with neurologic urinary tract disorders. Several pathological behaviours are in
      qualitative agreement with the model predictions.

PMID- 8759531
TI  - Organizing sensory information for postural control in altered sensory
      environments.
AB  - Healthy human subjects can maintain adequate balance despite distorted
      somatosensory or visual feedback or vestibular feedback distorted by a peripheral
      vestibular disorder. Although it is not precisely known how this sensorimotor
      integration task is achieved, the nervous system coordinates information from
      multiple sensory systems to produce motor commands differently in different
      sensory environments. These different ways of coordinating sensory information
      and motor commands can be thought of as "sensorimotor states". The way the
      nervous system distributes the monitoring of postural sway among states is
      analysed in this paper as a logical structure of transitions between states. The
      form of the transition structure is specified and distinguished from a finite
      state machine. The hypothesis that the nervous system could use a transition
      structure to maintain balance is tested by developing transition structures which
      are consistent with a set of experimental observations of postural control in
      healthy subjects and three groups of patients with peripheral vestibular disease.

PMID- 8759532
TI  - Barotitis in children after aviation; prevalence and treatment with Otovent.
AB  - Barotitis is an acute or chronic inflammation caused by environmental pressure
      changes. The most common cause is the pressure change during descent in civil
      aviation. To prevent barotitis the middle ear pressure has to be equalised
      several times during descent. This can be achieved by performing the Valsalva
      manoeuvre, but for children, many of whom have a dysfunction of the Eustachian
      tube, this is difficult to perform and they are therefore at high risk of
      developing barotitis during flight. The traditional treatment modalities of
      barotitis are inflation by a Politzer balloon, myringotomy or prophylactic
      grommet insertion. An alternative treatment or prophylactic measure is
      autoinflation using the Otovent treatment set. This prophylaxis/treatment can be
      performed by the child with assistance from its parents as soon as possible or
      rather before the descent has started. The prevalence of barotitis amongst
      transit passengers was found to be highest in young children, 25 per cent,
      compared with adults, five per cent. Only 21 per cent of the youngest children
      with negative middle ear pressure after flight managed a successful Valsalva's
      manoeuvre, whereas 82 per cent could increase the middle ear pressure inflating
      the Otovent set. In conclusion we recommend autoinflation using the Otovent set
      by children and adults with problems clearing the ears during flight.

PMID- 8759533
TI  - Configuration of experimentally produced cholesteatoma by transplantation of a
      free skin graft.
AB  - Residual cholesteatoma was experimentally produced in guinea pigs by
      transplanting a free skin graft into the middle ear bulla. In group A, the graft
      was placed on the mucosa after scratching the surface with a pick, while in group
      B, it was placed on the bone surface following removal of the mucosa and drilling
      with a diamond burr. The group A procedure was conducted on the left ear and the
      group B procedure on the right ear in 12 guinea pigs. The animals were sacrificed
      at two, four and eight weeks after transplantation. In all 12 ears of group A,
      the graft kept its original flat shape, resembling an open type residue. In eight
      of 12 ears of group B, the graft grew forming a squamous pearl, while in the
      remaining four ears it retained a flat shape. The difference in configuration is
      thought to be due to the amount of granulation around the graft.

PMID- 8759534
TI  - Facial nerve schwannoma: nerve fibre dissemination.
AB  - Biopsy of a middle ear mass can lead to facial paralysis when the mass is a
      facial nerve schwannoma. Immunostaining techniques were used to determine if
      nerve fibres might be present within the tumour mass. Nerve fibres were found to
      be widely disseminated throughout the tumour in eight of 23 facial nerve
      schwannomas. Antibodies to neurofilaments demonstrated single fibres, or small
      groups of fibres, that are very difficult to see with routine haematoxylin and
      eosin stains. The presence of fibres throughout some tumours makes biopsy of them
      likely to result in facial dysfunction.

PMID- 8759535
TI  - A clinical, genetic and audiological study of patients and families with
      unilateral vestibular schwannomas. I. Clinical features of neurofibromatosis in
      patients with unilateral vestibular schwannomas.
AB  - Ninety-three patients with unilateral vestibular schwannomas were examined in a
      clinical, genetic and audiological study, to determine whether they had features
      associated with neurofibromatosis Type 1 or neurofibromatosis Type 2. In 91
      families, one patient only was found to be affected with a unilateral vestibular
      schwannoma. Patients did have a few cafe-au-lait macules, but fewer than six in
      number. None of the patients satisfied the cutaneous diagnostic criteria for
      neurofibromatosis Type 1. Neither Lisch nodules nor presenile posterior
      subcapsular lenticular opacities or cortical opacities were a feature. Five
      patients with unilateral vestibular schwannomas are described where the clinical
      findings raised the possibility of neurofibromatosis Type 2. It is suggested that
      certain individuals with unilateral vestibular schwannomas are at risk of
      developing neurofibromatosis Type 2. Furthermore, the possibility of
      neurofibromatosis Type 2 should be considered if more than one individual in a
      family is found to be affected with a unilateral vestibular schwannoma.

PMID- 8759536
TI  - Analysis of CT scanning referrals for chronic rhinosinusitis.
AB  - The principal role of computed tomography (CT) scanning in rhinosinusitis is as a
      planning investigation for patients requiring functional endoscopic sinus surgery
      (FESS). The pre-operative scan is used to highlight any potential surgical
      hazards, and to delineate the extent of disease reducing unnecessary intervention
      in disease-free areas. It is inappropriate for CT to be used purely as a
      diagnostic investigation for chronic rhinosinusitis. As concern has been
      expressed over the steady rise in the referrals for CT of the sinuses, we
      conducted a retrospective review of all patients having these scans at two CT
      scanner sites in Scotland during 1993. Of the 162 scans performed for
      rhinosinusitis, 58 patients (36 per cent) had not had nasendoscopy performed or
      had a trial of medical treatment. Subsequently, only 61 patients (38 per cent)
      went on to FESS. The inappropriate use of CT for these patients can be reduced by
      insisting that nasendoscopy is performed prior to scanning. Furthermore,
      radiologists and surgeons should audit the number of patients not having FESS
      after scanning.

PMID- 8759537
TI  - Submucosal glands after maxillary sinus surgery. An experimental study in
      rabbits.
AB  - Thirty New Zealand White rabbits underwent unilateral partial or complete removal
      of maxillary sinus mucosa in order to evaluate submucosal maxillary sinus glands.
      After three months, specimens were taken for examination from all operated on and
      control sinuses. Bacteriological cultures, light and electron microscopy were
      performed. Histopathological findings showed a decrease in the number of serous
      glands and significant inflammation was present in the sinus in which there was
      complete surgical removal. Electron microscopy revealed changes in the secretory
      cells of the serous glands in the regenerated post-surgical mucosa.

PMID- 8759538
TI  - Incidental paranasal sinus inflammatory changes in a British population.
AB  - A retrospective study was carried out to determine the prevalence of abnormality
      in the paranasal sinuses in a British population having magnetic resonance
      imaging (MRI) scans for neurological signs and symptoms. The T2-weighted scans of
      130 patients were studied. Abnormalities in the paranasal sinuses show as high
      signal on the T2-weighted scans and thus are clearly seen. Abnormalities included
      mucosal thickening, fluid levels, sinus opacification and retention cysts/polyps.
      Of the patients studied, 49.2 per cent showed one or more abnormality. Mucosal
      thickening was the most common abnormality noted and the ethmoid sinuses the most
      commonly affected.

PMID- 8759539
TI  - Coherence analysis of EEG changes during odour stimulation in humans.
AB  - In a pilot study, EEG changes during odour administration were evaluated by
      coherence analysis. Ten normal adults were studied. Simultaneous recordings of 16
      EEG channels with, and without, odour administration were stored on magnetic tape
      for further processing. EEG signals were analysed using a signal analyser.
      Coherence spectra were calculated between all possible channel pairs on the
      scalp. The amount of data was reduced by extracting broad band coherence values
      for five frequency bands: delta (2-3.9 Hz), theta (4-7.9 Hz), alpha 1 (8-9.9 Hz),
      alpha 2 (10-12.9 Hz), and beta 1 (13-17.9 Hz). Coherence values extracted from
      the control EEG recordings and those during odour administration were compared to
      evaluate the presence of any significant differences. The results demonstrated
      significant changes in the EEG coherence between the two control recordings
      (control before and control after) in the theta and beta 1 bands. These frequency
      bands were therefore excluded from the examination. During odorant stimulation
      with methyl-cyclopentenolone, the coherence in the delta band decreased in the
      frontal region, while that in the alpha 1 and alpha 2 bands increased in the
      temporal region. During odorant stimulation with scatol, the coherence in the
      delta band decreased in the frontal region, while that in the alpha 1 and alpha 2
      bands increased between the longitudinal electrode locations. It was suggested
      that EEG coherence mapping may provide the basis for the development of an
      objective test of olfactory function in humans.

PMID- 8759540
TI  - Papillary and follicular thyroid carcinoma: the treatment results of 357 patients
      at the National Kyushu Cancer Centre of Japan.
AB  - During the period from April 1974 to March 1993, 357 patients received surgical
      treatment for papillary and follicular carcinoma of the thyroid gland at the
      Department of Head and Neck Surgery of National Kyushu Cancer Centre, Japan. In
      this paper, we review the various clinico-pathological features of these patients
      and analyse their influence on patient survival. While the majority of the
      patients' ages ranged from the third through seventh decade, only the patients
      older than 40 years old died. In papillary carcinomas, there was a statistically
      significant difference in the survival rate between younger (less than 45 years
      old) and older (45 years of age or older) patients. The rate of patients who died
      of thyroid cancer also increased in the cases with extra-thyroidal tumour
      invasion, and metastasis to distant organs. A multivariate analysis also showed
      that the age, extrathyroidal invasion and distant metastasis are significant
      prognostic factors. However, sex, histology and lymph node metastasis were not
      prognostic factors for survival.

PMID- 8759541
TI  - A complication of indoor pistol shooting.
AB  - The aetiology of chronic rhinitis and nasal obstruction is often elusive and
      obscure. Many different causes have been documented including allergens,
      cigarette smoke, cold dry air, viruses, sulphur dioxide and industrial
      pollutants. This is the first case we have been able to identify of rhinitis
      associated with exposure to high levels of lead through indoor pistol shooting.

PMID- 8759542
TI  - Unilateral choanal atresia in siblings--a rare occurrence.
AB  - The genetic aspects of choanal atresia have not been clearly defined though it is
      probably a multifactorial trait as in cleft lip and cleft palate. The appearance
      of the condition in both single and successive generations supports this
      contention. Choanal atresia can occur as an isolated anomaly, but is more
      commonly associated with one or more concomitant congenital anomalies. In this
      report two sisters both in their teens presented with unilateral choanal atresia
      as an isolated anomaly. Endoscopic trans-nasal repair of choanal atresia was
      performed in both of them as this offers excellent visualisation and access.

PMID- 8759543
TI  - Cryoglobulinaemia and septal perforation: a rare but logical cause.
AB  - A case of nasal septal perforation secondary to cryoglobulinaemia is reported. In
      this instance the cryoglobulinaemia was due to Waldenstrom's macroglobulinaemia
      (lymphoplasmocytic lymphoma with IgM paraprotein) in which the paraprotein was a
      potent cryoglobulin.

PMID- 8759544
TI  - Recurrent frontal sinusitis complicating orbital decompression in Graves'
      disease.
AB  - An unusual case of recurrent frontal sinusitis with abscess formation secondary
      to orbital decompression for Graves' disease is described. The infection was
      refractory to antibiotics treatment, external drainage and the sinus obliteration
      procedure. Since the sinus outflow was obstructed by prolapsing tissue following
      excessive removal of the orbital walls, sinus re-aeration by supporting the
      prolapsed tissue with a silastic sheet and stenting the sinus drainage tract was
      attempted. This led to a complete resolution of the infection with an excellent
      long-term result.

PMID- 8759545
TI  - Pitfalls in the determination of intracranial spread of complicated suppurative
      sinusitis.
AB  - We present two cases of suppurative sinusitis that presented to our casualty
      department over a one-week period. Both patients suffered complications of the
      disease secondary to extension of the inflammatory process beyond the bony
      confines of the sinus. Neither of the patients had a previous history of sinus
      disease. The first patient deteriorated suddenly 24 hours after admission. The
      initial computed tomography (CT) scan failed to demonstrate a developing subdural
      empyema. This complication was confirmed following repeat scanning 24 hours later
      and the patient required urgent neurosurgical intervention and drainage. The
      second patient presented with periorbital cellulitis secondary to sinusitis and
      suffered a grand mal seizure on admission. Once again initial CT scan changes
      were subtle and significant intracranial extension was not noted until the
      subsequent magnetic resonance imaging (MRI) scan was performed. The purpose of
      this paper is to highlight the potential dangers over reliance on CT scanning in
      diagnosing early intracranial spread of sinus disease and we emphasise that the
      clinician must interpret any radiological investigations in light of the
      associated clinical findings.

PMID- 8759546
TI  - Metastatic osteosarcoma of the ethmoid: an unusual cause of recurrent epistaxis
      and proptosis.
AB  - Osteosarcoma is the most common primary malignant tumour of bone and it usually
      metastasises to the lung. In the nasal cavity metastatic disease is extremely
      rare. We describe a case of osteosarcoma presenting with recurrent epistaxis, and
      proptosis due to secondaries in the nasal cavity. To our knowledge such a case
      has not been reported previously in the available English literature.

PMID- 8759547
TI  - An unusual foreign body in the larynx.
AB  - A case of a needle lodged in the larynx is reported. The needle had been inhaled
      via an asthma inhaler.

PMID- 8759548
TI  - Abductor vocal fold palsy in the Shy-Drager syndrome presenting with snoring and
      sleep apnoea.
AB  - The case of an elderly male with Shy-Drager syndrome is presented. His
      presentation to the Sleep Clinic for assessment of snoring illustrates bilateral
      abductor vocal fold palsy as a rare presentation of the syndrome. This case
      emphasizes the need for thorough investigation of all patients with sleep-related
      breathing disorders with video and sound recordings prior to anaesthesia and
      surgery.

PMID- 8759549
TI  - Oesophageal strictures in children: balloon or bougie dilatation?
AB  - The management of oesophageal strictures in neonates and infants is often by
      bougie dilatation. We report two cases in which balloon dilatation was used
      successfully and suggest that this may be a preferable technique in this age
      group.

PMID- 8759550
TI  - Spontaneous closure of acquired tracheo-oesophageal fistula.
AB  - Acquired tracheo-oesophageal fistulae are uncommon in the paediatric age group. A
      case of such a fistula secondary to impaction of a button battery is reported
      below. Prompt management is essential to reduce morbidity and mortality in these
      cases.

PMID- 8759551
TI  - Familial paraganglioma.
AB  - Non-secreting paragangliomas are rare tumours usually present in the head and
      neck. We describe an unusual case of familial paraganglioma with cranial nerve
      palsies. After exhaustive investigation, a vagal paraganglioma, was found and
      excised. The positive family history of paraganglioma was of significance,
      although this was only present in one of five generations. The diagnosis and
      management of non-secreting paragangliomas is discussed.

PMID- 8759552
TI  - Wegener's granulomatosis presenting as major salivary gland enlargement.
AB  - Salivary gland involvement is rare in Wegener's granulomatosis. We report the
      first case of widespread major salivary gland enlargement as part of the
      presentation of this disease. A review of the few reported cases in the
      literature suggests that salivary gland involvement may be associated with a
      limited form of the disease and an improved prognosis. The anti-neutrophil
      cytoplasmic antibody (c-ANCA) assay remains the gold standard of diagnosis but
      care should be exercised in the interpretation of results. This patient responded
      well to current immunosuppressive therapy.

PMID- 8759553
TI  - Aggressive cutaneous squamous cell carcinoma of the head and neck in patients
      with chronic lymphocytic leukaemia.
AB  - We describe multiple cutaneous squamous cell carcinomas of the head and neck in
      five patients with chronic lymphocytic leukaemia (CLL). When associated with CLL,
      cutaneous squamous cell carcinomata behave in a much more aggressive manner than
      otherwise expected. Four patients developed local recurrence after primary
      treatment. All five patients developed lymph node metastases containing squamous
      cell carcinoma. Three of five patients (60 per cent) had multiple primary
      lesions. Whereas the increased incidence of second cancers in CLL and notably of
      skin cancers is documented, little has been written to describe the aggressive
      behaviour of these tumours. It is important, when treating these patients, to be
      aware of the high tendency towards local recurrence and lymph node metastasis and
      to consider an aggressive management plan and careful follow-up.

PMID- 8759554
TI  - Chondroblastoma--an unusual site in a young patient.
AB  - We report a case of primary chondroblastoma presenting as a submucosal lump on
      the nasal bridge of a 15-year-old female. The lesion was curetted and the patient
      remains well after one year follow-up. This case report describes a primary
      chondroblastoma arising in an unusual site and in an unusual age group.

PMID- 8759555
TI  - Polymorphous low-grade adenocarcinoma of the tongue.
AB  - Primary adenocarcinomas of the oral cavity in minor salivary glands are
      distinctive lesions which can be subclassified according to their growth patterns
      or histomorphology. Polymorphous low-grade adenocarcinoma (PLGA) of minor
      salivary tissue has been recognized as a distinct entity. We report an unusual
      case of PLGA of the tongue. Only a few previous cases have been reported in the
      English literature. The treatment is discussed and a review of the current
      literature concerning this tumour is included.

PMID- 8759556
TI  - Are the morphology of papillary thyroid carcinoma and the tumour's behaviour
      correlated?
AB  - Six cases of papillary thyroid carcinoma showing clinically highly aggressive
      behaviour by invading the upper airway and digestive tract structures were
      retrospectively reviewed to evaluate the morphological variants of the tumours.
      Four of them were found to be pure papillary and one was a mixed-papillary and
      follicular-variants regarded as non-aggressive. Only one case was found to be
      tall cell variant-regarded as an aggressive variant of papillary thyroid
      carcinoma. The findings suggest that the prognosis of papillary thyroid carcinoma
      cannot be predicted from its morphological variant and attention should be given
      to other clinical parameters.

PMID- 8759557
TI  - Highly aggressive behaviour of occult papillary thyroid carcinoma.

PMID- 8759558
TI  - Pre-operative information in mastoidectomy: what about the facial nerve and
      hearing loss.

PMID- 8759559
TI  - Where would you choose to have a coronary angiogram?

PMID- 8759560
TI  - Testosterone, androgens and the risk of myocardial infarction.

PMID- 8759562
TI  - Postcholecystectomy problems and the role of endoscopic retrograde
      cholangiopancreatography.
AB  - Many patients continue to have symptoms even after cholecystectomy. We studied 4
      patients with postcholecystectomy problems over a period of seven years; 208 were
      females, males and their mean age was 41.8 years (range 14-70). Presenting
      symptoms were abdominal pain (217), jaundice (74), cholangitis (38) and external
      biliary fistula (eight). Fifteen patients also had a t-tube in situ. Endoscopic
      retrograde cholangiopancreatography was successfully performed in 239 patients
      and revealed abnormal findings in 179. These included: stones (89), strictures
      (53), choledochoduodenal fistula (10), choledochal cyst (three), biloma (three),
      ligation of bile duct (five), ascaris in bile duct (three), pancreatitis (nine),
      long cystic duct stump (11), and various other findings. Endoscopic
      sphincterotomy was carried out in 59 patients with stones. Seven patients with
      strictures were managed with stents. Ascaris in the bile duct of three patients
      was removed with the help of a Dormia basket. To conclude, stones and strictures
      are common postcholecystectomy problems and endoscopic retrograde
      cholangiopancreatography is very helpful in the diagnosis and management of
      postcholecystectomy patients.

PMID- 8759563
TI  - Parental knowledge and experiences after surgery for chronic otitis media.
AB  - Sixty-four parents completed questionnaires pertaining to their knowledge,
      attitudes and experiences both before and two months after their children
      underwent adenoidectomy and grommet insertion. Although a positive image of and
      high satisfaction with both procedure and inpatient stay were demonstrated, many
      parents failed to appreciate the existence, nature and frequency of possible
      complications. Parents should be given quite explicit descriptions of the most
      common postoperative problems.

PMID- 8759564
TI  - The effect of ranitidine (as effervescent tablets) on the quality of life of GORD
      patients.
AB  - Patients diagnosed as suffering from symptomatic reflux disease were entered into
      this comparative, multicentre study based in UK general practice. The study was
      designed to investigate the symptomatic response and quality of life of these
      GORD sufferers as they received ranitidine (Zantac effervescent tablets) over a
      four-week period. All patients initially received ranitidine 150 mg bd for two
      weeks. Subsequent treatment was allocated according to symptomatic response:
      responders remained on the initial dose for the remaining two weeks of the study,
      non-responders had their dosage increased to qds. Quality of life was assessed
      using the short-form 36 questionnaire (SF-36) both before and two and four weeks
      after treatment. The GORD sufferers had a significantly worse quality of life
      than a representative sample of the general population before treatment. After
      just four weeks of treatment with ranitidine, however, substantial improvements
      were observed in all domains of the SF-36, to the extent that the quality of life
      profile of the GORD sufferers became very similar to that of the general
      population and no significant differences were observed between the groups.

PMID- 8759566
TI  - Current methods to reduce the adverse haematological consequences of
      cardiopulmonary bypass.
AB  - Bleeding remains a significant cause of morbidity after cardiac surgery and
      results in a major demand on blood transfusion capacity. The aetiology is
      multifactorial, but platelet dysfunction is the most important cause. Because of
      the potential risks of heterologous blood transfusion, a number of techniques
      have been developed to reduce its need. These can broadly be divided into three
      categories. First, modification of bypass methods and the use of agents such as
      aprotinin can reduce blood loss. Second, more use can be made of the patient's
      own blood through predonation of autologous blood or blood conservation
      techniques. Finally, transfusion policy can be modified so that a lower
      postoperative haemoglobin level is accepted. However, a method with which to
      preoperatively predict those patients who will bleed significantly remains
      elusive.

PMID- 8759567
TI  - Benign paroxysmal positional vertigo.
AB  - Benign paroxysmal positional vertigo should be considered when a patient
      complains of attacks of dizziness of brief duration, that seem to occur under
      particular circumstances related to the position of the head. The true nature of
      the disorder may be missed unless examination is carried out in a certain way:
      the head must be positioned below the rest of the body and turned to one or other
      side. Diagnosis then depends on the occurrence of vertigo and on noting the
      transient nystagmus. There are a number of causes of benign paroxysmal positional
      vertigo-head injury is a relatively frequent one. It has been suggested that this
      disorder is due to deposits on the cupula of the precipitating posterior
      semicircular canal. Indeed, exercises designed to dislodge such deposits can be
      successful. If not, and the vertigo lasts for more than a few months, surgery can
      be considered.

PMID- 8759565
TI  - Pain control after hysterectomy: an observer-blind, randomised trial of
      lornoxicam versus tramadol.
AB  - This 24-hour, randomised, double-blind, placebo-controlled study compared the
      efficacy and tolerability of intravenous injections of lornoxicam 4 mg and 8 mg
      with tramadol 50 mg in 78 female patients aged 20-65 years with moderate to
      intolerable postoperative pain following mainly hysterectomy. Patients who
      received lornoxicam 8 mg had a significantly (p < 0.05) longer time to first
      remedication than placebo recipients and tended to have a greater reduction in
      pain intensity and a longer time to withdrawal due to "non-response' than
      tramadol and placebo patients. Lornoxicam was well tolerated at both doses and
      was associated with a lower incidence of adverse events than tramadol. Thus,
      intravenous lornoxicam at a dose of 8 mg is superior to placebo and at least as
      effective as intravenous tramadol 50 mg in relieving moderate to intolerable post
      hysterectomy pain. Furthermore, lornoxicam seems to possess a more favourable
      tolerability profile than tramadol.

PMID- 8759568
TI  - Alendronate: a new bisphosphonate for the treatment of osteoporosis.
AB  - Alendronate is a drug with considerable potential. It is likely to work best in
      elderly patients with moderate to severe osteoporosis. Long-term studies and
      comparison with other therapeutic agents are needed before its exact role is
      established.

PMID- 8759569
TI  - Conference review: scientific session of the American College of Cardiology 1996.
AB  - Several truly "landmark' studies were presented during the 45th Annual Scientific
      Session of the American College of Cardiology (ACC). This report reviews studies
      of markers of atherosclerosis and some of the trials in endothelial dysfunction
      (TREND), lipid lowering (CARE), coronary angioplasty and unstable angina (EPILOG,
      CAPTURE, RESTORE), acute myocardial infarction (HERO, GUSTO 11b), post-myocardial
      infarction (EMIAT, CAMIAT), and heart failure (DIG trial).

PMID- 8759570
TI  - Myocardial infarction with extensive intracoronary thrombus induced by anabolic
      steroids.
AB  - Anabolic steroids have been associated with a variety of adverse reactions,
      including myocardial infarction. We report two cases of myocardial infarction in
      young men on anabolic steroids. In both men, extensive intracoronary thrombosis
      was demonstrated at coronary angiography; this failed to resolve despite
      anticoagulation.

PMID- 8759571
TI  - Acalculous cholecystitis in patients with acute leukaemia.
AB  - Cases of acalculous cholecystitis in patients with acute leukaemia are rare.
      Manifestations of the primary disease often mask the acute cholecystitis
      symptoms. A high index of suspicion and ultrasonographic examination in leukaemic
      patients with abdominal pain and unexplained fever may allow earlier diagnosis,
      before the development of complications. We report two cases of acute acalculous
      cholecystitis during the course of acute leukaemia.

PMID- 8759572
TI  - A new method for rapid, percutaneous, sheathless insertion of the intra-aortic
      balloon.
AB  - Rapid insertion of the intra-aortic balloon (IAB) via the femoral artery is
      sometimes necessary. The increasing age of patients in cardiac units means that
      insertion into atherosclerotic and stenosed vessels can lead to ischaemic
      complications, particularly when the sheath is used. We present a modified method
      for rapid, percutaneous insertion of the sheathless IAB using the sheath dilator
      supplied with the insertion kit.

PMID- 8759573
TI  - Lymphocytic pleural exudate in a patient receiving amiodarone.
AB  - We present a patient who developed a unilateral, exudative pleural effusion
      without concomitant pulmonary parenchymal disease while being treated with
      amiodarone. Previous attempts to discontinue amiodarone therapy and substitute
      alternative antiarrhythmics resulted in recurrence of life-threatening
      arrhythmias. We chose to continue amiodarone and observe the response to a brief
      course of oral corticosteroids. The pleural effusion resolved quickly and had not
      recurred after 36 months of observation.

PMID- 8759574
TI  - Acute-phase mental health consequences of disasters: implications for triage and
      emergency medical services.

PMID- 8759575
TI  - Report on 640 victims of the Tokyo subway sarin attack.

PMID- 8759576
TI  - Triage: techniques and applications in decision making.
AB  - Correct decision making may have far-reaching consequences. Triage is an area in
      which decision-makers must know what they are doing, why they are doing it, and
      which actions to take to achieve a satisfactory outcome. Triage has its origins
      in military history and today is used in a variety of medical settings. In this
      article we focus on the role of triage in disaster situations, its application in
      military settings, and its use in disaster medicine. Useful concepts enabling
      correct decision making by the triage officer include the application of computer
      technology and a review of methods of patient categorization. The dynamic nature
      of triage and the role of the triage officer as part of a team approach to
      disaster patient management are highlighted. We explore techniques for the
      successful training and education of triage officers and investigate a model of
      the emergency physician as the triage officer.

PMID- 8759577
TI  - Analgesic practice for acute orthopedic trauma pain in Costa Rican emergency
      departments.
AB  - STUDY OBJECTIVE: Studies in US emergency departments have demonstrated that pain
      is undertreated in adults and children. Previous studies have also demonstrated
      cultural differences in the expression and perception of pain. The objective of
      this investigation was to describe the analgesic practices and patient pain
      responses in two Costa Rican EDs in light of possible differences due to cultural
      variation. METHODS: We carried out a prospective, noninterventional observational
      assessment protocol of a convenience sample of patients being treated for
      orthopedic trauma in two university-affiliated urban teaching hospital EDs.
      Children between the ages of 5 and 12 years and all adults, ages 16 to 63, who
      presented with painful orthopedic trauma were included. Patients quantified their
      pain on arriving at and before leaving the ED. Children used a Face Interval
      Scale ranging from 1 (no pain) to 9 (maximum pain), and adults used a numeric
      rating scale ranging from 0 to 10. RESULTS: One fourth of pediatric and more than
      half of all adult patients had no reduction in their pain scores on leaving the
      ED. Eleven percent of adults and fewer than 4% of children received pain
      treatment while in the ED. Fewer than half of all patients were sent home with
      analgesics. We observed no use of opioids in the ED for analgesia. CONCLUSION:
      Our data illustrate that both adults and children with severe pain resulting from
      orthopedic injury in the Costa Rican EDs we studied often receive inadequate or
      no analgesic treatment. This finding suggests that the phenomenon of
      oligoanalgesia is more widespread and resistant to cultural differences. We also
      noted a reluctance to use opioids in this setting.

PMID- 8759578
TI  - Comparison of intravenous ketorolac, meperidine, and both (balanced analgesia)
      for renal colic.
AB  - STUDY OBJECTIVE: To compare the analgesic efficacy and safety of IV ketorolac,
      the only nonsteroidal antiinflammatory drug indicated for parenteral use in acute
      pain in the United States, with IV meperidine and with a combination of the two
      agents in renal colic. METHODS: We carried out a double-blind, randomized,
      multicenter clinical trial in the emergency departments of four urban tertiary
      care teaching hospitals. Our study subjects were 154 patients with suspected
      renal colic. Each subject received an initial IV dose of ketorolac 60 mg,
      meperidine 50 mg, or both supplemented as needed beyond 30 minutes with
      additional doses of meperidine. RESULTS: The main outcome measures were changes
      in pain-intensity and pain-relief scores, amount of supplemental meperidine
      required, end-of-study drug tolerability, and adverse events. Analyses of 106
      subjects with confirmed renal colic indicated that ketorolac and the combination
      were significantly better than meperidine alone by all efficacy measures,
      including pain relief and time elapsed before the need for supplemental
      meperidine. By 30 minutes, 75% of the ketorolac group and 74% of the combination
      group had a 50% reduction in pain scores, compared with 23% of the meperidine
      group (P < .001). The ketorolac and combination groups did not differ
      significantly in any of the efficacy measures. CONCLUSION: IV ketorolac, alone or
      in combination with meperidine, was superior to IV meperidine alone in moderate
      and severe renal colic. Because many subjects in all three treatment groups
      received supplemental meperidine and because response to ketorolac alone cannot
      be predicted, clinicians may choose to initiate treatment with a ketorolac
      meperidine combination.

PMID- 8759579
TI  - Factors associated with unrecognized HIV-1 infection in an inner-city emergency
      department.
AB  - STUDY OBJECTIVE: To determine the prevalence of and risk factors associated with
      unrecognized HIV-1 infection among medical patients presenting to an inner-city
      emergency department. METHODS: We conducted anonymous HIV-1 testing in subjects
      interviewed for risk behaviors and knowledge of HIV status at an inner-city ED in
      the Bronx, New York. Our subjects were consecutive adult medical patients in
      noncritical condition (N = 1,744) who were evaluated by three physicians
      providing primary emergency care. Each patient was given a structured interview
      for demographic characteristics, risk behaviors, and knowledge of HIV status.
      Excess serum, drawn for clinical purposes, was linked without identifiers to
      responses and tested for antibodies to HIV-1. In subjects who denied HIV
      infection, we tested associations with seropositivity using univariate analyses
      and logistic-regression techniques (multivariate). RESULTS: Of the 1,744 patients
      interviewed, 656 (37.6%) reported HIV risk behaviors. Of 970 tested for HIV-1
      antibodies, 125 (12.9%) were seropositive. The prevalence of HIV-1 infection
      among those who denied known infection was 4.0% (35 of 875). In the multivariate
      model, independent predictors of unrecognized HIV-1 infection were age 35 to 44
      years, crack cocaine use, history of syphilis, and ED diagnosis of an infection
      not necessarily related to HIV infection. Unrecognized HIV-1 infection was more
      likely among patients admitted to the hospital, but 21 of the 35 with
      unrecognized infection (60%) were not admitted and in 9(25.7%) no risk factors
      were identified. CONCLUSION: More than one third of patients who visited one
      inner-city ED acknowledged HIV risk behaviors. One quarter of patients with
      unrecognized HIV-1 infection reported no identifiable risk factors. Easily
      accessible HIV counseling and testing should be considered in EDs in areas
      serving persons at risk for HIV infection.

PMID- 8759581
TI  - Nonfatal firearm injuries in New Zealand, 1979-1992.
AB  - STUDY OBJECTIVE: To describe the epidemiology of serious non-fatal firearm injury
      in New Zealand. METHODS: Cases of nonfatal firearm-related injury were extracted
      from the hospital inpatient data files of the New Zealand Health Information
      Service for the period 1979 to 1992 inclusive. RESULTS: There were 1,239 firearm
      related injuries, or 2.7 injuries per 100,000 population per year. Males, persons
      aged 15 to 24 years, certain occupational groups, and persons living in rural
      environments had higher rates of injury. Unintentional incidents accounted for
      64% of the injuries. At least 25% of the incidents involved shotguns, and a
      further 20% involved rifles. CONCLUSION: The results presented here serve to
      support the attention that has been given to prevention of firearm injuries in
      New Zealand. Priority should be given to establishment of a surveillance system
      that would provide uniform data on firearm-related mortality and morbidity to aid
      in risk factor research and development and evaluation of intervention programs.

PMID- 8759580
TI  - Primary varicella in adults: pneumonia, pregnancy, and hospital admission.
AB  - STUDY OBJECTIVE: To define the rate of complications of adult varicella,
      including pneumonia, and to determine the association of such complications with
      pregnancy. METHODS: Retrospective, descriptive case series of consecutive adult
      emergency department patients with primary varicella seen over a 31-month period
      in an urban county hospital. RESULTS: A total of 130 patients were identified,
      with a mean age of 23.9 +/- 6.1 years; 69 (53%) were female. Thirteen patients
      (10.0%) had pneumonia; 6 of these were hospitalized. Two patients admitted with
      pneumonia had significant underlying comorbid disease and expired from
      respiratory failure. The remaining 4 admitted patients recovered uneventfully.
      Four of the 7 patients discharged with pneumonia were known to have recovered
      uneventfully. Twenty-eight (41%) of the 69 female study patients were pregnant; 7
      of these (25%) were admitted, with admission diagnoses of pneumonia (1), active
      labor (2), and pregnancy with varicella (4). Incidence of pneumonia in pregnant
      patients was 3.6% (1 of 28; 95% confidence interval, 1% to 18.3%). All 7 admitted
      pregnant patients and the 19 (of 21) discharged pregnant patients who were
      contacted recovered uneventfully. No congenital anomalies or perinatal
      complications were noted in the infants of the 26 mothers with documented follow
      up. CONCLUSION: Hospital admission should be considered for adults with varicella
      pneumonia, especially if they have significant comorbid disease. It does not
      appear that pregnant women are at increased risk of developing varicella
      pneumonia.

PMID- 8759582
TI  - Epidemiology of firearm mortality and injury estimates: state of Connecticut,
      1988-1993.
AB  - STUDY OBJECTIVES: To retrospectively determine the 6-year cumulative incidence
      rate of firearm mortality and estimate nonfatal firearm injuries in Connecticut.
      METHODS: Retrospective analysis of data originating from the Connecticut State
      Medical Examiner's Office and records from the Trauma Registry of one urban
      hospital. RESULTS: From January 1988 through December 1993, 1,625 Connecticut
      residents died from firearm-related injuries. The cumulative incidence rate was
      49.4 deaths per 100,000 population during the 6-year study period. Rates peaked
      among 20- to 24-year-olds at 18.1 deaths per 100,000. Males outnumbered females
      more than eightfold. The ratio of nonfatal firearm injuries to firearm deaths was
      7:1 for those shot by another, self-inflicted injuries were fatal in half of all
      cases. CONCLUSION: Analysis of firearm mortality data indicated that males in
      younger age categories were disproportionately affected. These rates combined
      with nonfatal injury projections demonstrate that firearms represent a
      significant public health threat to the population of Connecticut, reaching
      epidemic proportions among specific subpopulations. These results are consistent
      with those obtained from national studies.

PMID- 8759583
TI  - Safety of imaging exploding bullets with ultrasound.
AB  - STUDY OBJECTIVE: To evaluate the safety of using ultrasound to image exploding
      bullets that have not detonated. METHODS: We evaluated various types of exploding
      bullets using ultrasonography at various depths with various transducers and
      using standard radiography. RESULTS: None of the unexploded bullets subjected to
      ultrasonography or standard radiography exploded. CONCLUSION: Our results suggest
      that evaluation of exploding bullets with ultrasonography is safe.

PMID- 8759584
TI  - Evaluation of the emergency department logbook for population-based surveillance
      of firearm-related injury.
AB  - STUDY OBJECTIVE: To evaluate existing emergency department logbooks as a source
      of population-based data on firearm-related injuries. METHODS: We examined the
      logbooks of the 24 acute care and specialty-hospital EDs in Allegheny County,
      Pennsylvania, to determine the number and type of data variables each contained
      and the completeness of reporting of each variable for selected firearm-related
      cases. The amount of missing data for certain variables was determined and the
      cause for the missing data described. RESULTS: Logbooks from 18 of the 24
      eligible hospitals were reviewed. We identified 785 cases of firearm-related
      injury recorded between January 1, 1992, and December 31, 1993. Of the variables
      we selected for analysis, only date (100%), chief complaint or diagnosis (100%),
      name (98%), and time of admission (97%) were consistently documented. In 37% of
      cases the patient's county of residence could not be determined. Similarly
      incomplete data were found for body part injured (31%), race (28%), age (26%),
      sex (22%), and mode of arrival (21%). The factor most responsible for the high
      percentage of incomplete data was the considerable variation in the data elements
      contained in the different hospitals' logbooks. CONCLUSION: Missing data
      resulting from inconsistencies in the variables contained in different EDs'
      logbooks and errors of omission prevent ED logbooks, in their current state, from
      providing population-based data for surveillance of firearm-related injury.
      Standardization of such variables in ED logbooks would yield a more useful source
      of information for injury and disease surveillance. In lieu of standardized
      logbooks, multiple sources of data are necessary to establish a more
      comprehensive and useful system of surveillance of firearm-related injury.

PMID- 8759585
TI  - Gunshot wound review.
AB  - There is no serious argument about the wounding potential of various kinds of
      penetrating projectiles. The laws of physics in concert with modern bullet
      testing have clarified and quantified the mechanisms by which bullets disrupt
      tissue. Despite this scientific background, much misinformation persists in the
      wound-ballistics literature. The article reviews the interaction of penetrating
      projectiles with human tissue. Understanding of wound allows the emergency
      physician to become a more informed reader of its literature, as well as a more
      reliable provider of care to the wounded patient.

PMID- 8759586
TI  - Firearm violence among youth: public health strategies for prevention.
AB  - Firearm violence is a serious threat to the health of our children: an American
      child dies of gunshot wounds every 1 1/2 hours, and every 2 days 30 children--the
      equivalent of a school classroom--lose their lives to guns. Injured children and
      adolescents are cared for in emergency departments and trauma centers, and in
      some urban areas the increasing incidence of firearm injuries threatens to
      overwhelm the trauma care delivery system. Because of the prevalence and enormous
      cost of firearm violence it has been identified as an epidemic and a public
      health emergency. In this article we discuss the burden of firearm injury and its
      effect on children and young adult, and we outline a public health approach to
      firearm injury prevention.

PMID- 8759587
TI  - Method to electronically collect emergency department data.
AB  - STUDY OBJECTIVE: To describe the development and completeness of an electronic
      injury-surveillance system, the Rural Injury Surveillance System (RISS). METHODS:
      The emergency departments of nine rural Iowa hospitals submitted information on
      all patients treated from May 1993 through June 1994. RESULTS: The EDs submitted
      information on 23,594 patients with 32,445 different injury, disease, or follow
      up visits. On the basis of comparison with the handwritten ED logbook, 90% of
      visits were also available in the RISS. Of the visits recorded in the RISS, 99%
      were also recorded in the logbook. The proportion of missing diagnostic codes
      decreased from a high of 22.6% in May 1993 to 8.1% in June 1994. The proportion
      of missing external cause codes was about 25% at the end of the study period. The
      proportion of missing industry and occupational codes was less than 5% at the end
      of the study period. CONCLUSION: Our findings show that complete, computerized,
      ED-based injury surveillance in rural EDs is possible and should be developed
      further.

PMID- 8759588
TI  - External emergency medical disaster response: does a need exist?

PMID- 8759589
TI  - Chemical agent terrorism.

PMID- 8759590
TI  - Diagnostic testing: a call for continuing investigation [corrected].

PMID- 8759591
TI  - Rapid identification of group A streptococcus as the cause of necrotizing
      fasciitis.
AB  - Group A beta-hemolytic Streptococcus pyogenes (GAS) causes a spectrum of highly
      aggressive, invasive infections. We report two cases of necrotizing fasciitis in
      which GAS was identified as the presumptive causative organism with the use of
      the standard rapid streptococcal diagnostic kit. We believe the rapid test kits
      may be a useful adjunct in the diagnosis and treatment of this catastrophic
      illness and may play a role in limiting the spread of infection.

PMID- 8759592
TI  - Presentation of Ehlers-Danlos syndrome: iliac artery pseudoaneurysm rupture.
AB  - We present a case of acute flank and groin pain resulting from a ruptured left
      iliac artery with pseudoaneurysm in a patient with previously undiagnosed Ehlers
      Danlos syndrome (EDS). EDS is an uncommon, heterogeneous disease of abnormal
      collagen production with potentially fatal sequelae. The nine major types of EDS
      have varying clinical manifestations and degrees of severity. Type IV EDS is of
      special concern in that it is frequently associated with life-threatening
      vascular complications such as arterial aneurysm formation with rupture and
      dissection. EDS should be suspected in young people with vascular complications,
      recurrent joint dislocations, or fragile skin. In patients with known EDS,
      abdominal, flank, or pelvic pain should be investigated promptly to rule out life
      threatening complications involving the vascular system, gastrointestinal tract,
      or gravid uterus.

PMID- 8759593
TI  - Scombroid poisoning.
AB  - Scombroid poisoning is described in the literature as a toxic poisoning caused by
      ingestion of certain dark meat fish undergoing bacterial decomposition. Poisoning
      results from the ingestion of a heat-stable toxin. We describe the case of a man
      who presented to the emergency department several hours after eating tuna steak
      with evidence of scombroid poisoning that was associated with loss of vision and
      atrial tachycardia with block. All signs and symptoms resolved after treatment
      for scombroid poisoning.

PMID- 8759594
TI  - Meningococcal sequelae.

PMID- 8759595
TI  - Air bag alert. National Highway Traffic Safety Administration.

PMID- 8759596
TI  - Air bags and the teachable moment.

PMID- 8759597
TI  - Health care reform revisited.

PMID- 8759598
TI  - Diagnosis of ventricular tachycardia.

PMID- 8759599
TI  - Myoglobin and creatine kinase-MB.

PMID- 8759600
TI  - Shoulder reduction.

PMID- 8759601
TI  - Hot liquid aspiration and child abuse.

PMID- 8759602
TI  - Loss of heterozygosity on chromosome 1 in human hepatoblastoma.
AB  - In previous studies we have found loss of heterozygosity (LOH) on chromosome arm
      11p in 33% of hepatoblastomas (HBs). In addition, cytogenetic studies have
      revealed aberrations of chromosome arm 1p in single cases. Therefore, we have
      used the PCR to amplify 10 microsatellites on the short arm and 7 microsatellites
      on the long arm of chromosome I to assess allelic loss in 32 cases of HB. LOH on
      chromosome I was found in II cases. Seven HBs showed LOH on chromosome Ip, 7
      cases had LOH on Iq, and 3 tumors had LOH on both Ip and Iq. Six HBs with LOH on
      Ip had LOH at DIS243 (Ip36.3), and one tumor had a loss at DIS80 maintaining
      heterozygosity at DIS243. A common region of overlap was present at the telomeric
      chromosomal portion of Ip between DIS80 and DIS243. Of the HBs with LOH on Iq, 4
      showed a common region of overlap at Iq3I-q32.I, and the other 3 at DISI609
      located more telomerically. The parental origin of the lost allele was of random
      distribution for chromosome arm Ip and of paternal origin for chromosome arm Iq.
      Our data suggest that tumor suppressor genes located at the telomeric region of
      chromosome arm Ip and different regions of chromosome arm Iq may be involved in
      the pathogenesis of HB.

PMID- 8759603
TI  - A population-based study of cancer risk in twins: relationships to birth order
      and sexes of the twin pair.
AB  - One thousand and sixty-three twins with cancer whose co-twin was born alive were
      identified among patients born since September 1939 with cancers incident in
      England and Wales during 1971-1984 at childhood and young adult ages. Site
      specific risks of cancer were analysed in relation to birth order within the
      twinship and sexes of the twin pair, using adjusted national birth data to give
      control distributions of these variables. Risk of leukaemia was increased in
      first-born twins, risk of testicular cancer was increased in second-born twins
      with female co-twins but decreased in second-born twins with male co-twins and
      lung cancer risk was increased in first-born twins with same-sex co-twins.
      Cutaneous melanoma risk was increased in persons with opposite-sex co-twins,
      nervous system cancer risk was increased in females with opposite-sex co-twins
      and Hodgkin's disease risk was increased in persons with same-sex co-twins. For
      most of the findings, no previous comparable analyses are available, so
      interpretation of the results must be provisional until the analyses can be
      repeated on other data. The result for leukaemia would accord with previous
      suggestions that leukaemia may be of prenatal origin and may sometimes lead to
      intrauterine death. The Hodgkin's disease result would fit with theories of an
      infectious aetiology, and this view is strengthened by reanalysis of previous
      data on paralytic poliomyelitis in twins, which show a pattern similar to that
      for the Hodgkin's disease patients. Cancer risk in relation to birth order and
      sex of twins can give novel, objective data relating to prenatal and infectious
      disease aetiology of cancers.

PMID- 8759604
TI  - Gene expression of DNA topoisomerases I, II alpha and II beta and response to
      cisplatin-based chemotherapy in advanced ovarian carcinoma.
AB  - DNA topoisomerases, nuclear enzymes that regulate DNA topology, are recognized as
      the primary targets of effective anti-tumor drugs. These enzymes may also have a
      role in the repair of DNA damage induced by alkylating agents and platinum
      compounds; therefore, their expression may be a determinant of tumor response to
      chemotherapy. Our study was undertaken in an attempt to establish a correlation
      between the enzyme expression and response of ovarian cancer to cisplatin-based
      chemotherapy. The expression of topoisomerase I, II alpha and II beta genes was
      assessed by RNase protection assay in tumor specimens obtained from 37 untreated
      patients with advanced epithelial ovarian cancer at initial surgery and from 13
      pre-treated patients at subsequent laparotomy. The expression levels were
      compared with those found in 5 specimens from benign ovarian tissue and 5
      specimens from normal ovarian tissue. The expression levels in untreated patients
      were used to establish a correlation with response to high-dose cisplatin
      therapy. A significant intertumor variability of mRNA expression was noted for
      all the genes examined. However, a comparison of median values indicated a
      remarkable increase of expression in malignant tumors over benign or normal
      tissues only for topoisomerase II alpha. This change is not related to
      alterations or amplification of topoisomerase II alpha gene. Interestingly, a
      correlation was found between tumor response to chemotherapy and the expression
      level of the isoform alpha (but not of topoisomerase II beta and topoisomerase
      I). The observed correlation suggests a contribution of the enzyme in determining
      tumor sensitivity. Alternatively, increased expression levels of the alpha
      isoenzyme gene in responsive tumors might reflect higher fractions of
      proliferating tumor cells that may be more drug-sensitive than resting cells.

PMID- 8759605
TI  - Naevi and pigmentary characteristics as risk factors for melanoma in a high-risk
      population: a case-control study in New South Wales, Australia.
AB  - The relationship between risk of cutaneous malignant melanoma and total body and
      site-specific naevus counts and other host factors was investigated in a
      Caucasian population aged 15-84 years in New South Wales, Australia. The study
      sample comprised 244 cases with melanoma diagnosed in 1989-1993, and 276
      controls. The strongest relationship was with total body naevus count. Risk of
      melanoma was raised 12 times in those with more than 100 naevi compared with
      those with less than 10. There were also strong risks, with odds ratios of 5 or
      more, associated with having multiple atypical naevi, multiple large naevi, high
      naevus counts in sun-exposed or sun-protected areas and being unable to tan on
      repeated sun exposure. The effect of inability to tan was stronger at younger
      than older ages. Lesser risks, with odds ratios of 2-3, were associated with
      being prone to burn on sun exposure, having many freckles as a child and having
      red hair. The site distribution of naevi in males compared with females resembled
      the distribution of melanoma by sex. Risk of melanoma of the back was
      significantly more closely related to back naevus count than naevus count for the
      remainder of the body. For other anatomical sites, naevus count was non
      significantly more closely related to naevus counts at that site than counts over
      the remainder of the body. Naevus count declined with age in both cases and
      controls. In those aged under 40, having 100 or more naevi was associated with an
      aetiological fraction (AF) of 41%. In those aged 60 and over, however, the AF
      associated with this number of naevi was only 5%.

PMID- 8759606
TI  - Expression of cathepsin E in pancreas: a possible tumor marker for pancreas, a
      preliminary report.
AB  - Ductal cancers of the pancreas frequently express markers of gastrointestinal
      epithelial cells. Cathepsin E (CTSE) is a non-secretory, intracellular, but non
      lysosomal proteinase found in the highest concentration in the superficial
      epithelial cells of the stomach. The aims of our study were to examine the
      expression of CTSE in the pancreas, to establish an assay system of CTSE and to
      evaluate the diagnostic usefulness of CTSE in the pancreatic juice. Eleven
      patients with pancreatic ductal adenocarcinoma, 10 with mucin-producing adenoma,
      3 with intraductal papillary hyperplasia and 43 with chronic pancreatitis were
      examined. Surgically resected pancreatic tissues were subjected to
      immunohistochemistry for CTSE. Pancreatic juice was collected from the patients
      and subjected to sandwich ELISA and Western analysis for detecting CTSE. Positive
      staining for CTSE was observed in pancreatic ductal adenocarcinoma by
      immunohistochemistry. CTSE was also expressed in mucin-producing adenoma,
      intraductal papillary hyperplasia and mucinous hyperplasia. CTSE in the
      pancreatic juice was present in 8 of 11 patients with pancreatic ductal
      adenocarcinoma, 5 of 10 patients with mucin-producing tumor, 1 of 3 patients with
      intraductal papillary hyperplasia and 4 of 43 patients with chronic pancreatitis.
      The detection frequency of CTSE in the pancreatic juice was significantly higher
      in the patients with pancreatic ductal adenocarcinoma than in the patients with
      chronic pancreatitis. Our findings suggest that the expression of CTSE is
      associated with the pathogenesis of pancreatic ductal adenocarcinoma, that CTSE
      in the pancreatic juice seems to be a useful marker for a definitive diagnosis
      and that CTSE may be expressed at a relatively early stage of multistep
      carcinogenesis in pancreatic lesions.

PMID- 8759607
TI  - Lymphoma, myeloma and occupation: results of a case-control study.
AB  - The known risk factors for lymphoma and myeloma cannot account for the current
      incidence rates of these cancers, and there is increasing interest in exploring
      occupational causes. We present results regarding lymphoma and myeloma from a
      large case-control study of hundreds of occupational exposures and 19 cancer
      sites. We examine in more detail those exposures previously considered to be
      related to these cancers, as well as exposures which were strongly related in our
      initial analyses. Lymphoma was not associated in our data with exposure to
      solvents or pesticides, or employment in agriculture or wood-related occupations,
      although numbers of exposed cases were sometimes small. Hodgkin's lymphoma was
      associated with exposure to fabric dust, and non-Hodgkin's lymphoma was
      associated with exposure to copper dust, ammonia and a number of fabric and
      textile-related occupations and exposures. Employment as a sheet metal worker was
      associated with development of myeloma.

PMID- 8759608
TI  - Time trend and age-period-cohort effect on incidence of thyroid cancer in
      Connecticut, 1935-1992.
AB  - Recent studies from Europe suggest a continuing increase in thyroid cancer, but
      it is unclear whether this trend also applies to the United States. The current
      study examined the long-term trend of thyroid cancer in Connecticut. Our results
      show that the overall age-adjusted incidence rate of thyroid cancer has been
      increasing in Connecticut, from 1.30/100,000 in 1935-1939 to 5.78/100,000 in 1990
      1992 in females, and from 0.30/100,000 in 1935-1939 to 2.77/100,000 in 1990-1992
      in males. The increase mainly comes from papillary carcinoma of the thyroid. The
      birth cohort analyses indicate that the increase in thyroid cancer occurred among
      cohorts born between 1915 and 1945, which experienced an increase of 31.4% every
      5 years in males and 17.3% in females over the period 1960-1979. For those born
      since the 1945 cohort, the incidence has been decreasing, at rates of 9.3% and
      8.3% every 5 years over the period 1975-1992 in males and females, respectively.
      Age-period-cohort modeling results also suggest a strong birth cohort effect on
      the observed time trend in both sexes, which closely follows the introduction of
      radiation treatment of benign childhood conditions in the head and neck between
      1920 and the 1950s in the United States. Our results are consistent with the
      suggested radiation hypothesis, indicating that radiation treatment of benign
      childhood conditions in the head and neck is largely responsible for the observed
      increase of thyroid cancer in Connecticut.

PMID- 8759609
TI  - Evidence for two distinct tumor-suppressor gene loci on the long arm of
      chromosome 11 in human oral cancer.
AB  - Loss of heterozygosity (LOH) on human chromosome 11 has been reported in a
      variety of human cancers. To search for the existence of tumor-suppressor gene(s)
      associated with oral squamous cell carcinoma (SCC) on chromosome 11, we have
      performed high-resolution deletion mapping in 31 patients with oral SCC using 22
      microsatellite markers for this chromosomal region. LOH was observed in 14 of 25
      cases (56.0%) that were informative with at least one locus. Most allelic
      deletions detected in our study were specific to the long arm of the chromosome.
      Furthermore, the data presented here show 2 distinct, commonly deleted regions.
      The first region, with frequent LOH, was restricted between markers DIIS939 and
      DIIS924 separated by 3 centimorgans (cM) on chromosome 11q23. The second region
      of common deletion was identified between markers DIIS912 and DIIS910, separated
      by 7 cM at 11q25. Our results suggest that at least 2 tumor-suppressor genes
      involved in the development of oral SCC are present on the long arm of chromosome
      11.

PMID- 8759610
TI  - Second primary tumors in patients with hereditary retinoblastoma: a register
      based follow-up study, 1945-1994.
AB  - The aim of this register-based follow-up study was to evaluate the long-term
      cumulative incidence of second primary tumors (SPT) among survivors of hereditary
      retinoblastoma, with special interest for the incidence of pineoblastoma in
      retinoblastoma patients born after 1970. The Dutch Retinoblastoma Register was
      completed and updated: in the period 1945-1994, 639 retinoblastoma patients were
      registered. The vital status of each patient was obtained from the municipal
      registries and the Central Office of Genealogy. SPT were traced and
      histopathologically confirmed. Survival curves and cumulative incidence of SPT
      were calculated by the Kaplan-Meier method. The survival of patients with
      hereditary retinoblastoma was significantly shorter than that of patients with
      non-hereditary retinoblastoma. The cumulative incidence of SPT in hereditary
      patients was 3.7 and 17.7% at the ages of 10 and 35 years, respectively. Long
      term follow-up revealed a high proportion of melanomas (7 melanomas out of 28
      SPT). In the sub-cohort of the hereditary-retinoblastoma patient group born after
      1970, the cumulative incidence of pineoblastomas at the age of 5 years was 9.3%.
      Our results suggest that patients with hereditary retinoblastoma should have
      careful follow-up, and procedures for diagnosing SPT and pineoblastomas at an
      early and potentially treatable stage should be developed.

PMID- 8759611
TI  - Effects of mass screening on age-specific incidence of neuroblastoma.
AB  - Using data from the Japan Children's Cancer Registry, we estimated the age
      specific incidence rates of neuroblastoma. Before the neuroblastoma screening
      program started in 1985, the age-standardized incidence rates of neuroblastoma
      ranged from 7.5 to 9.1 x 10(-6) for children under 15 years of age. After the
      introduction of the screening program, the annual incidence rate rose to 19.5 x
      10(-6). The annual incidence rate for neuroblastoma in children under 1 year of
      age was 150.60 x 10(-6) in the years 1989 to 1992, whereas the incidence rates
      only varied between 23.6 and 34.13 x 10(-6) in the 3 preceding 5-year periods.
      This increase in incidence for infants was accompanied by a minor decrease in
      incidence for children 2 to 3 years of age. However, this decrease may only
      partly explain the large increase in incidence for infants. Therefore, we suggest
      that screening may result in the detection of otherwise spontaneously regressing
      tumors. It is urgent to determine the contribution of screening to decreasing
      mortality before deciding whether this screening program should be continued.

PMID- 8759612
TI  - Pharmacological inhibition of gelatinase B induction and tumor cell invasion.
AB  - The 92 kDa matrix metalloproteinase (gelatinase B, MMP-9) plays a major role in
      the facilitation of tumor metastasis and in inflammatory disorders characterized
      by excessive matrix protein destruction. MMP-9 is transcriptionally induced in
      multiple cell types by exposure to the inflammatory mediators bacterial
      endotoxin, interleukin-1 (IL-1) or tumor necrosis factor-alpha (TNF-alpha). CT
      2519, (1-(5-isothiocyanatohexyl)-3,7-dimethylxanthine), a synthetic small
      molecule from an anti-inflammatory compound library, was evaluated for its effect
      on endotoxin and cytokine-induced MMP-9 synthesis by a monocytic leukemic cell
      line, THP-1, and a monocyte/macrophage line, RAW 264.7. CT-2519 dose-dependently
      inhibited endotoxin and cytokine-induced synthesis of MMP-9 by these cells.
      Furthermore, both MMP-9 secretion and matrix invasion by cells of a human
      fibrosarcoma cell line, HT-1080, were inhibited by CT-2519 in a dose-dependent
      manner. Northern blot analyses and studies utilizing MMP-9 promoter constructs
      indicated that the inhibitory action of CT-2519 occurs at the level of
      transcriptional suppression. Given the observation that cellular activation by
      endotoxin, IL-1 and TNF-alpha may be mediated, at least in part, through
      induction of certain species of phosphatidic acid (PA), the effect of CT-2519 on
      lipid levels was analyzed. CT-2519 effectively reduced endotoxin-mediated
      increases in particular cellular lipid levels. Pharmacologic modulation of
      cytokine-dependent gene products, such as MMP-9, may offer an important
      therapeutic approach to the treatment of neoplastic and inflammatory disorders.

PMID- 8759613
TI  - Growth-independent induction of spermidine transport by IL-4 and IL-13 in ZR-75-1
      human breast cancer cells.
AB  - Polyamine transport is strongly induced by insulin and estradiol (E2) in ZR-75-1
      human breast cancer cells. Because signal transduction mechanisms of insulin and
      interleukin-4 (IL-4) partly overlap, we have compared the ability of these agents
      as well as that of interleukin-13 (IL-13), a cytokine that often mimics IL-4, to
      modulate spermidine transport in these cells. In the presence of E2, insulin
      increased DNA content and the rate of [3H]spermidine uptake by 2.1- and 3.7-fold,
      respectively, after an 8-day incubation, whereas the sole addition of IL-4 caused
      a quantitatively similar induction of [3H]spermidine uptake while leaving cell
      growth unaffected. No comparable induction of spermidine transport was observed
      with interleukins-1 alpha and -6, and the effect of IL-4 was not additive to that
      elicited by insulin plus E2. IL-4 and IL-13 stimulated [3H]spermidine uptake to a
      comparable extent, with half-maximal effects observed at 80 and 400 pg/ml,
      respectively. Interferon-gamma inhibited IL-4- and IL-13-dependent spermidine
      uptake to a much greater extent than basal or insulin-induced transport of the
      polyamine. IL-4 and IL-13 increased the Vmax and K(m) of [3H]spermidine uptake by
      about 4- and 2.5-fold, respectively. Na(+)-dependent amino acid uptake was
      increased by insulin but not by IL-4 or IL-13, indicating that the cytokines do
      not induce a general increase in membrane transport activity. IL-4 and IL-13 did
      not interfere with feedback inhibition of polyamine uptake, and only modestly
      decreased polyamine content after prolonged incubation, suggesting that these
      cytokines stimulate spermidine uptake by increasing total transport capacity
      rather than by repressing and endogenous inhibitor.

PMID- 8759614
TI  - Maintenance of growth factor signaling through Ras in human colon carcinoma cells
      containing K-ras mutations.
AB  - Fifty percent of human colon carcinomas contain activating mutations in the K-ras
      gene. However, whether these alterations in K-ras affect the function of Ras
      proteins in growth factor (GF) signal transduction is now known. Here we have
      characterized a previously defined human colon carcinoma cell model system for K
      ras gene mutations and for altered levels of Ras protein expression and have
      examined whether these alterations affect Ras function in GF signal transduction.
      Sequence analysis of PCR-amplified K-ras gene fragments indicated that among the
      more aggressive cell lines, four had a normal K-ras sequence, whereas 3 others
      (isolated from the same human tumor) contained a mutation at codon 13. In
      contrast, all 7 of the less aggressive cell lines contained a mutation at either
      codon 12 or 13. In addition to the presence of a K-ras mutation, one cell line
      expressed higher levels of the K-Ras protein and displayed elevated Ras-GTP
      loading (in the absence of GF addition) compared with the other cell lines
      examined. Despite these alterations, the mitogenic GF combination epidermal
      growth factor + insulin + transferrin resulted in an activation of Ras and
      extracellular signal-regulated kinase 2. Collectively, our results indicate that
      the malignant phenotype of the cell lines was not correlated with the presence of
      K-ras mutations or with higher levels of Ras protein expression. Furthermore, K
      ras mutations, high levels of K-Ras protein expression, and elevated Ras-GTP
      loading, as they occur naturally in human colon carcinomas, do not abolish the
      function of Ras in GF signaling.

PMID- 8759615
TI  - Activation of cathepsin B, secreted by a colorectal cancer cell line requires low
      pH and is mediated by cathepsin D.
AB  - The aim of our study was to identify changes in secreted procathepsin B levels in
      a model of the human colorectal adenoma to carcinoma sequence and to determine
      the factors required for its extracellular activation. Conversion of the non
      tumorigenic adenoma-derived cell line PC/AA to a highly tumorigenic phenotype
      (designated AA/CI/SB10/M) was associated with an 8-fold increase in the presence
      of the proform of cathepsin B in 24 hr conditioned serum-free medium (SFM). In
      addition, mature enzyme was only detected in the cell lines of this model with
      increased malignant potential. This is in agreement with the findings of a
      previous study, in which mature cathepsin B was only present in the 24 hr
      conditioned SFM of cancer-derived cell lines and not in SFM from adenoma-derived
      cell lines. Having demonstrated a reduction in the pH of conditioned medium from
      cell lines with increased malignant potential, we used a range of specific
      proteinase inhibitors to show that an aspartyl proteinase was involved in the
      initial activation of procathepsin B. Consistent with this finding, we
      subsequently demonstrated an increased secretion of the aspartyl proteinase
      cathepsin D in the medium of the AA/CI/SB10/M adenocarcinoma cells compared with
      the non-tumorigenic AA/Cl cell line. Therefore, the presence of mature cathpsin B
      in the conditioned medium of the more malignant cell lines coincided with a
      reduction in pH and an increase in the amount of cathepsin D secreted. Data from
      the human colorectal derived adenoma to carcinoma sequence indicate that an in
      vivo mechanism may exist that, dependent on the simultaneous presence of both a
      tumour-generated acidic extracellular environment and an elevated secretion of
      procathepsin D, could result in the activation of latent procathepsin outside the
      cell.

PMID- 8759616
TI  - Interstitial and transurethral photodynamic therapy of the canine prostate using
      meso-tetra-(m-hydroxyphenyl) chlorin.
AB  - Photodynamic therapy (PDT) produces localised necrosis with light after prior
      administration of a photosensitising drug. Although the technique is promising
      for small tumours of hollow organs, little work has been done on solid organs
      like the prostate. We studied the tissue biodistribution and photodynamic effects
      of meso-tetra-(m-hydroxyphenyl) chlorin (mTHPC), a potent second-generation
      photosensitiser, on normal canine prostate in vivo. Using quantitative
      fluorescence microscopy, the highest concentration of mTHPC in the prostate was
      seen 24-72 hr after intravenous administration. For PDT, red light (650 nm) was
      delivered to the prostate by laser fibres inserted via the transurethral or
      transperineal route under transrectal ultrasound guidance. PDT lesions up to 40
      mm in diameter (using 4 fibre sites) were produced, characterised by swelling,
      inflammatory response and extensive glandular destruction. There was persistent
      glandular atrophy at 90 days, but no disruption of the main stroma and no change
      in the ultimate size or shape of the gland. Urethral damage sometimes caused
      temporary urinary retention, but this resolved by 7 days, and no animal became
      incontinent. Occasional small lesions were seen in the rectum, but these healed
      without sequelae and there were no fistulae. Since cancer and normal prostate are
      likely to respond similarly, PDT has considerable promise for treating cancer
      confined to the gland as large areas of glandular tissue can be necrosed with
      safe healing. Because the structural integrity of the gland is maintained, PDT is
      unlikely to be of value in the management of benign prostatic hypertrophy.

PMID- 8759617
TI  - Spontaneous de-differentiation correlates with extended lifespan in transformed
      thyroid epithelial cells: an epigenetic mechanism of tumour progression?
AB  - Normal thyroid follicular cells, like many highly differentiated epithelia, have
      limited proliferative capacity. We previously showed that this could be extended
      by expression of the SV40 large T oncogene, but that immortal lines always lost
      thyroid-specific differentiation. Detailed analysis now show that clones
      expressing T undergo 2 mutually exclusive fates. They either (i) remain well
      differentiated, in which case they undergo irreversible growth arrest after 5 to
      15 p.d., or (ii) spontaneously develop poorly differentiated sub-clones that
      exhibit greatly extended proliferative life spans (up to 75 p.d.). The frequency
      of this event (> 3 per 10(4) cell divisions) greatly exceeds that expected from
      somatic mutation, suggesting an epigenetic basis. This is supported by our
      finding of rare de-differentiated epithelial cells in normal thyroid that all
      generate clones with extended life spans, indistinguishable from the above,
      following introduction of SV40 T. Escape from early mortality in differentiated
      thyroid epithelium therefore requires not only loss of tumour suppressor gene
      function (induced here by SV40 T), but also a switch in differentiation
      programme, with the latter effectively converting the follicular cell into a cell
      type with increased intrinsic proliferative potential. The analogy between this
      in vitro model and the progression of thyroid cancer from the well-differentiated
      to the highly aggressive, anaplastic form suggests that de-differentiation may
      play a causal rather than a passive role in this critical switch in tumour
      behaviour.

PMID- 8759618
TI  - Estrogen induces apoptosis in a rat prostatic adenocarcinoma: association with an
      increased expression of TGF-beta 1 and its type-I and type-II receptors.
AB  - Rats transplanted with the androgen-sensitive Dunning R3327 PAP prostatic
      adenocarcinoma were castrated and treated with either estrogen or vehicle alone
      for short periods (4 hr, 12 hr, 24 hr) and for 6 weeks. In these tumors the
      expression of TGF-beta 1, TGF-beta type-I and type-II receptors (TGF-beta RI, TGF
      beta RII) was examined by immunohistochemistry. Apoptotic cells were identified
      by in situ nick and labelling (TUNEL). Tumor growth was retarded by castration
      and even more by additive estrogen treatment. The epithelium of the untreated
      tumors stained weakly for TGF-beta 1 and TGF-beta RI, but TGF-beta RII was not
      detected. Castration induced moderate TGF-beta 1 immunoreactivity in a major part
      of the glandular epithelium after 24 hr. After 12 hr already, castration plus
      estrogen resulted in an intense staining for TGF-beta 1 in the basal epithelial
      cells, some of which also showed an apoptotic appearance. The percentage of cells
      having stained positive for TGF-beta 1 was significantly higher in the estrogen
      treated groups than in the castrated group after 12 hr, and its elevated TGF-beta
      1 level remained at 6 weeks. Notably, the increased immunoexpression of TGF-beta
      1 occurred before the onset of induction of apoptosis. In parallel with the
      upregulation of TGF-beta 1 after castration, the expression of its receptors. TGF
      beta RI and RII, was induced and was further enhanced by the additive estrogen
      treatment. The number of intensely stained TGF-beta 1 tumor cells showed a strong
      correlation with the number of apoptotic tumor cells identified by TUNEL in the
      whole material. Furthermore, TGF-beta 1 immunoreactivity co-localized with the
      presence of apoptotic cells in the estrogen-treated tumors at 6 weeks after
      castration.

PMID- 8759619
TI  - Anti-estrogens enhance the therapeutic effect of lymphokine-activated killer
      cells on the P815 murine mastocytoma.
AB  - Tamoxifen (TX) and toremifene (TO) enhanced the lysis of P815 mastocytoma cells
      in vitro by syngeneic DBA2 spleen cells that have been activated by human
      recombinant interleukin-2 (IL-2) for 6 days (lymphokine-activated killer [LAK]
      cells). Similarly, enhanced tumor suppression occurred when TX- or TO-treated
      P815 cells were mixed with LAK cells and injected s.c. into normal DBA2
      recipients. Tumor suppression could be increased further by treating such
      recipients orally with TX or TO and by the repeated injections of LAK cells into
      the tumor site. The treatment of animals bearing tumors (5 mm in diameter) orally
      with TX or TO or with LAK cells i.p. resulted in tumor suppression. When the drug
      treatment was combined with LAK cells, tumor suppression was more pronounced, and
      complete tumor regression was induced in a significant number of the animals so
      treated. Our results indicate that the immunotherapeutic effect of LAK cells can
      be significantly amplified by combined treatment with the anti-estrogens TX or
      TO.

PMID- 8759620
TI  - Scientific and ethical issues of computer-linked records.

PMID- 8759621
TI  - Structural abnormality of 1q in an AIDS-related body-cavity-based lymphoma.

PMID- 8759622
TI  - Identification of a retinoic acid receptor alpha subtype specific agonist.

PMID- 8759623
TI  - Potent thrombin inhibitors that probe the S1 subsite: tripeptide transition state
      analogues based on a heterocycle-activated carbonyl group.

PMID- 8759624
TI  - Potent inhibition of tumor necrosis factor-alpha production by
      tetrafluorothalidomide and tetrafluorophthalimides.

PMID- 8759625
TI  - Mechanism-based inhibition of L-pipecolate oxidase by 4,5-dehydro-L-pipecolic
      acid.

PMID- 8759626
TI  - Neighborhood behavior: a useful concept for validation of "molecular diversity"
      descriptors.
AB  - When searching for new leads, testing molecules that are too "similar" is
      wasteful, but when investigating a lead, testing molecules that are "similar" to
      the lead is efficient. Two questions then arise. Which are the molecular
      descriptors that should be "similar"? How much "similarity" is enough? These
      questions are answered by demonstrating that, if a molecular descriptor is to be
      a valid and useful measure of "similarity" in drug discovery, a plot of
      differences in its values vs differences in biological activities for a set of
      related molecules will exhibit a characteristic trapezoidal distribution
      enhancement, revealing a "neighborhood behavior" for the descriptor. Applying
      this finding to 20 datasets allows 11 molecular diversity descriptors to be
      ranked by their validity for compound library design. In order of increasing
      frequency of usefulness, these are random numbers = log P = MR = strain energy <
      connectivity indices < 2D fingerprints (whole molecule) = atom pairs =
      autocorrelation indices < steric CoMFA fields = 2D fingerprints (side chain only)
      = H-bonding CoMFA fields.

PMID- 8759627
TI  - Bioisosterism as a molecular diversity descriptor: steric fields of single
      "topomeric" conformers.
AB  - The comparative molecular field analysis steric field of a single "topomeric"
      conformer is introduced as a molecular diversity descriptor particularly useful
      for combinatorial chemistry involving variations around a fixed "core". Using
      this new descriptor, 736 commercially available thiols are divided into 231
      bioisosteric clusters, whose compositions agree at least as well with medicinal
      chemical experience and intuition as do clusters derived from Tanimoto
      differences between 2D fragment occurrences. However, in practice topomeric
      steric fields complement 2D fingerprints, being the two most frequently useful
      descriptors yet found for neighborhood-based design of combinatorial libraries.

PMID- 8759628
TI  - Synthesis and structure-activity relationships of 2-pyridones: a novel series of
      potent DNA gyrase inhibitors as antibacterial agents.
AB  - Two novel series of 2-pyridones were synthesized by transposition of the nitrogen
      of 4-quinolones to the bridgehead position. This subtle interchange of the
      nitrogen atom with a carbon atom yielded two novel heterocyclic nuclei,
      pyrido[1,2-alpha]pyrimidine and quinolizine, which had not previously been
      evaluated as antibacterial agents and were found to be potent inhibitors of DNA
      gyrase. Quinolizines with a methyl group at the 9-position such as (S)-45a (ABT
      719) demonstrate exceptional broad spectrum antibacterial activity. Most notably,
      they are active against resistant bacteria such as methicillin-resistant
      Staphylococcus aureus, vancomycin-resistant strains of enterococci, and
      ciprofloxacin-resistant organisms. In addition, 2-pyridones also possess
      favorable physiochemical and pharmacokinetic properties. These 2-pyridones were
      synthesized from the commercially available starting materials by 10-17 linear
      transformations. The structure of an adduct yielded by this sequence, (S)-45a
      (ABT-719), was determined by X-ray crystallographic analysis.

PMID- 8759629
TI  - Synthesis of 2-amido-2,3-dihydro-1H-phenalene derivatives as new conformationally
      restricted ligands for melatonin receptors.
AB  - Tetrahydroanthracene, tetrahydrophenanthrene, and tetrahydrophenalene moieties
      were used to design novel constrained melatoninergic agents. Compounds 1 and 2
      were synthesized from the cyclization of the aryl succinic acids 6a,b followed by
      catalytic reduction, Curtius degradation to the amino derivatives, and
      acetylation. The phenalene derivatives 3 were prepared by cyclization of the aza
      lactones of the corresponding alpha-N-acetyl amino acids. The ketone derivatives
      were reduced directly by catalytic hydrogenation to produce the compounds 3. The
      different compounds were evaluated in vitro in binding assays using 2-[125I]
      iodomelatonin and chicken brain membranes. Melatonin and 2-acetamido-8
      methoxytetralin were used as the reference compounds. The results showed the
      superiority of the dihydrophenalene framework 3 over those of
      tetrahydroanthracene and tetrahydrophenanthrene. 3a had relatively good affinity
      for melatonin receptors (Ki = 28.7 nM). Introduction of an additional methoxy
      group gave a derivative (3c) with nanomolar affinity (Ki = 0.7 nM), confirming
      the existence of a secondary binding site in the receptor which has been
      described previously. An increase in the affinity was also observed with the
      propionamido derivative 3e (Ki = 6.0 nM). The potential agonist properties of the
      compound 3e were evaluated on the dermal melanocytes of Xenopus laevis tadpoles.
      At the concentration of 2.3 nM (5 x Ki), melatonin gave a melanophore index value
      of 1. Similarly to melatonin, 3e was shown to be a potent agonist of the
      melanosome aggregation.

PMID- 8759630
TI  - Evaluation of the stability and animal biodistribution of gadolinium (III)
      benzylamine-derivatized diethylenetriaminepentaacetic acid.
AB  - The need for a readily available Gd(III) bifunctional chelate for protein
      conjugation has led to the development of LDTPA (N,N-bis[2-[N',N'
      bis(carboxymethyl)amino]- ethyl]-4-amino-L-phenyl-alanine). The benzylamine group
      is readily converted to the isothiocyanato group (SCN-LDTPA) by treatment of the
      lithium salt of LDTPA with thiophosgene. SCN-LDTPA was successfully conjugated to
      three proteins, BSA (bovine serum albumin), mannose BSA, and galactose BSA. All
      protein conjugates were labeled with 111In3+ or 153Gd3+. Competition of Gd-LDTPA
      with DTPA (diethylenetriaminepentaacetic acid) resulted in a log stability
      constant of 21.2. The thermodynamic stability constant of Gd-LDTPA was also
      measured. The log Gd(III) stability constant (log K) is 21.99, and the log
      protonation constants (pKa's) are 10.16, 8.92, 5.35, 3.93, 2.71, and 1.89.
      Comparison of the thermodynamic stability constants for Gd(LDTPA)2- with other
      DTPA derivatives indicates that the stability of Gd(LDTPA)2- is similar to
      Gd(DTPA)2- (log K = 22.4), and higher than DTPA derivatives with one or more
      carboxylate arm(s) functionalized. The biodistribution of 153Gd-LDTPA-protein
      conjugates is consistent with the in vitro stability measurements. By monitoring
      the bone accumulation of 153Gd3+, 153Gd-LDTPA-protein shows a higher in vivo
      stability than 153Gd-DTPA-protein, the radiolabeled protein conjugate formed by
      the reaction of DTPA dianhydride with proteins.

PMID- 8759631
TI  - De novo antimicrobial peptides with low mammalian cell toxicity.
AB  - De novo antimicrobial peptides with the sequences: (KLAKKLA)n, (KLAKLAK)n (where
      n = 1,2,3), (KALKALK)3, (KLGKKLG)n, and (KAAKKAA)n (where n = 2,3), were prepared
      as the C-terminus amides. These peptides were designed to be perfectly
      amphipathic in helical conformations. Peptide antibacterial activity was tested
      against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus.
      Peptide cytotoxicity was tested against human erythrocytes and 3T3 mouse
      fibroblasts. The 3T3 cell testing was a much more sensitive test of cytotoxicity.
      The peptides were much less lytic toward human erythrocytes than 3T3 cells.
      Peptide secondary structure in aqueous solution, sodium dodecylsulfate micelles,
      and phospholipid vesicles was estimated using circular dichroism spectroscopy.
      The leucine/alanine-containing 21-mers were bacteriostatic at 3-8 microM and
      cytotoxic to 3T3 cells at about 10 microM concentrations. The leucine/alanine- or
      leucine/glycine-containing 14-mers and the leucine/glycine 21-mer were
      bacteriostatic at 6-22 microM but had much lower cytotoxicity toward 3T3 cells
      and higher selectivities than the natural antimicrobial peptides magainin 2 amide
      and cecropin B amide. The 7-mer peptides are devoid of biological activity and of
      secondary structure in membrane mimetic environments. The 14-mer peptides and the
      glycine-containing 21-mer show modest levels of helicity in model membranes. The
      leucine/alanine-containing 21-mer peptides have substantial helicity in model
      membranes. The propensity to alpha-helical conformation of the peptides in
      amphipathic media is proportional to their 3T3 cell cytotoxicity.

PMID- 8759632
TI  - Peptidyl anthraquinones as potential antineoplastic drugs: synthesis, DNA
      binding, redox cycling, and biological activity.
AB  - A series of new compounds containing a 9,10-anthracenedione moiety and one or two
      peptide chains at position 1 and/or 4 have been synthesized. The amino acid
      residues introduced are glycine (Gly), lysine (Lys), and tryptophan (Trp), the
      latter two in both the L- and D-configurations. The peptidyl anthraquinones
      maintain the ability of intercalating efficiently into DNA, even though the
      orientation within the base-pair pocket may change somewhat with reference to the
      parent drugs mitoxantrone (MX) and ametantrone (AM). The interaction constants of
      the mono-, di-, and triglycyl derivatives are well comparable to those found for
      AM but 5-10 times lower than the value reported for MX. On the other hand, the
      glycyl-lysyl compounds bind DNA to the same extent as (L-isomer) or even better
      than (D-isomer) MX. As for the parent drugs without peptidyl chains, the new
      compounds prefer alternating CG binding sites, although to different extents. The
      bis-Gly-Lys derivatives are the least sensitive to base composition, which may be
      due to extensive aspecific charged interactions with the polynucleotide backbone.
      As far as redox properties are concerned, all peptidyl anthraquinones show a
      reduction potential very close to that of AM and 60-80 mV less negative than that
      of MX; hence, they can produce free-radical-damaging species to an extent similar
      to the parent drugs. The biological activity has been tested in human tumor and
      murine leukemia cell lines. Most of the test anthraquinones exhibit cytotoxic
      properties close to those of AM and considerably lower than those of MX.
      Stimulation of topoisomerase-mediated DNA cleavage is moderately present in
      representatives of the glycylanthraquinone family, whereas inhibition of the
      background cleavage occurs when Lys is present in the peptide chain. For most of
      the test anthraquinones, the toxicity data are in line with the DNA affinity
      scale and the topoisomerase II stimulation activity. However, in the lysyl
      derivatives, for which lack of cytotoxicity cannot be related to poor binding to
      DNA, the steric and electronic properties of the side-chain substituent must
      impair an effective recognition of the cleavable complex.

PMID- 8759633
TI  - Synthesis and evaluation of phorboid 20-homovanillates: discovery of a class of
      ligands binding to the vanilloid (capsaicin) receptor with different degrees of
      cooperativity.
AB  - A number of phorboid 20-homovanillates were prepared by condensation of phorbol
      12,13-diesters and 12-dehydrophorbol 13-esters with Mem-homovanillic acid
      followed by removal of the protecting group with SnCl4 in THF. These compounds
      were evaluated for their ability to inhibit [3H]resiniferatoxin (RTX) binding to
      rat spinal cord membranes. Compounds bearing a lipophilic ester group on ring C
      were considerably active, but a surprising tolerance of the vanilloid receptor
      toward the location and the orientation of this ester group was disclosed.
      Unexpectedly, these ligands could also diminish, to a variable degree, the
      positive cooperativity which characterizes RTX binding to the vanilloid receptor.
      Phorbol 12-phenylacetate 13-acetate 20-homovanillate (PPAHV, 6a), a compound
      which abolished binding cooperativity, was further tested in a variety of in vivo
      assay used to characterize vanilloid-like activity. PPAHV showed only a marginal
      pungency and failed to induce a measurable hypothermia response at doses (up to
      200 mg/kg) at which it effectively desensitized against neurogenic inflammation.
      These data suggest that the peculiar binding behavior of these ligands might be
      associated with a distinct spectrum of biological activity.

PMID- 8759634
TI  - Antipsoriatic anthrones with modulated redox properties. 3. 10-thio-substituted
      1,8-dihydroxy-9(10H)-anthracenones as inhibitors of keratinocyte growth, 5
      lipoxygenase, and the formation of 12(S)-HETE in mouse epidermis.
AB  - The synthesis of a series of 1,8-dihydroxy-9(10H)-anthracenones bearing sulfur
      linked substituents in the 10-position is described. These compounds were
      evaluated for their ability to inhibit the growth of the human keratinocyte cell
      line HaCaT and the 5- and 12-lipoxygenase enzymes in bovine polymorphonuclear
      leukocytes and mouse epidermal homogenate, respectively. In addition, the
      following redox properties of the compounds were determined: reactivity against
      2,2-diphenyl-1-picrylhydrazyl, generation of hydroxyl radicals as measured by
      deoxyribose degradation, and inhibition of lipid peroxidation in model membranes.
      Compounds 4e and 4h of this series compare favorably in the cellular assays with
      the antipsoriatic anthralin. They have the combined inhibitory action against
      leukotriene B4 and 12(S)-HETE formation and are highly potent antiproliferative
      agents against keratinocyte growth. In contrast to anthralin, 4h, 1,8-dihydroxy
      10-[(4-hydroxyphenyl)thio]-9(10H)-anthracenone, is not cytotoxic as documented by
      the LDH activity released from cytoplasm of keratinocytes and does not enhance
      lipid peroxidation in model membranes.

PMID- 8759635
TI  - Orally active fibrinogen receptor antagonists. 2. Amidoximes as prodrugs of
      amidines.
AB  - The potent and selective GP IIb-IIIa antagonist lamifiban (1, Ro 44-9883) is
      currently in clinical development as an injectable antithrombotic agent for
      treating and preventing acute coronary syndromes. However, for secondary
      prevention of thrombotic occlusions, orally active inhibitors are needed. By
      means of a prodrug strategy, the modest oral absorption of 1 in mice was improved
      by a factor of 9. In addition, these studies demonstrated that an amidoxime group
      can serve as a prodrug functionality for an amidino group. Application of this
      principle to the structurally related amidino carboxylate 13 led to the amidoxime
      ester 18 which was absorbed approximately 20 times better, after oral
      administration to mice, than 13. Due to the modification of the amidino group as
      well as of the carboxylate group, 18 completely lost its ability to interact with
      purified platelet GP IIb-IIIa. After oral administration of 18 to rats, dogs, and
      rhesus monkeys, the bioavailability of the active derivative 13 was 26 +/- 5, 25
      +/- 6, and 33 +/- 6%, respectively, and the elimination half-life was 4.1 +/-
      1.7, 11.4 +/- 1.1, and 5.1 +/- 1.4 h, respectively. On the basis of these
      properties, the orally active 18 (Ro 48-3657), a double prodrug of the potent and
      selective non-peptide GP IIb-IIIa antagonist 13 (Ro 44-3888), was selected as
      clinical candidate for evaluation as a prophylactic agent in patients at high
      risk for arterial thrombosis.

PMID- 8759636
TI  - Structure-activity relationships of (E)-3-(1,4-benzoquinonyl)-2-[(3-pyridyl)
      alkyl]-2-propenoic acid derivatives that inhibit both 5-lipoxygenase and
      thromboxane A2 synthetase.
AB  - As part of our research for the development of novel antiinflammatory drug
      candidates, we have designed and synthesized a series of (E)-3-(1,4
      benzoquinonyl)-2-[(3-pyridyl)alkyl]-2-propenoic acid derivatives as dual
      inhibitors of 5-lipoxygenase (5-LO) and thromboxane (TX) A2 synthetase. In order
      to increase the absorption after oral administration, we introduced a carboxylic
      acid moiety into the 1,4-benzoquinone skeleton, which has 5-LO-inhibitory
      character. Introduction of a 3-pyridylalkyl group at the double bond of the 1,4
      benzoquinonyl propenoic acid moiety afforded good to moderate inhibitory
      activities against the production of leukotriene (LT) B4 and TXA2 while not
      significantly inhibiting that of prostaglandin E2 by glycogen-induced peritoneal
      cells of rat (in vitro). The length of the methylene chain of the 3-pyridylalkyl
      group influenced the inhibition of LTB4 and TXB2 production. An increase of
      lipophilicity by introducing a more lipophilic alkoxy group did not markedly
      increase the inhibitory activity on LTB4 production. The position of alkoxy group
      on the 1,4-benzoquinone skeleton played an important role in TXA2 synthetase
      inhibition. Compounds such as 20c (E6700) with an appropriate alkoxy group and
      proper length of methylene side chain, together with a polar substituent
      (carboxylic acid), showed good inhibition of both 5-LO and TXA2 synthetase and
      possess a variety of pharmacologically beneficial effects.

PMID- 8759637
TI  - Mercaptoacyl dipeptides as orally active dual inhibitors of angiotensin
      converting enzyme and neutral endopeptidase.
AB  - Dual inhibitors of the two zinc metallopeptidases, neutral endopeptidase (NEP, EC
      3.4.24.11) and angiotensin-I-converting enzyme (ACE, EC 2.4.15.1), have been the
      focus of much clinical interest for the treatment of hypertension and congestive
      heart failure. We have previously reported that compound 2 (N-[[1-[(2(S)-mercapto
      3-methyl-1-oxobutyl) amino]-1-cyclopentyl]-carbonyl]-L-tyrosine) was a potent
      dual inhibitor in vitro (IC50 (ACE) = 7.0 nM, IC50 (NEP) = 1.5 nM) (Fink et al.
      J. Med. Chem. 1995, 38, 5023-5030). This compound was found to have oral
      activity; however, its duration of effect was short. A series of thioacetate
      carboxylic acid ester analogs of compound 2 was prepared. Modifications were also
      made to the tyrosine phenol. These compounds were evaluated for their ability to
      inhibit plasma ACE activity when administered orally to conscious normotensive
      rats. Most of the compounds prepared were found to be orally active with longer
      durations of effect than compound 2. Compound 38 (N-[[1-[(2(S)-(acetylthio)-3
      methyl-1-oxobutyl) amino]-1-cyclopentyl]carbonyl]-O-methyl-L-tyrosine ethyl
      ester), administered at 11.7 mg/kg po, was found to be more efficacious than
      captopril at 10 mg/kg po. This compound was also found to inhibit plasma NEP
      activity following oral administration to conscious rats and was more efficacious
      than acetorphan. Compound 38 was found to lower blood pressure in the aorta
      ligated rat and the spontaneously hypertensive rat when administered orally. The
      synthesis and biological activity of these dual inhibitors are discussed.

PMID- 8759638
TI  - Synthesis and characterization of pseudopeptide bradykinin B2 receptor
      antagonists containing the 1,3,8-triazaspiro[4.5]decan-4-one ring system.
AB  - A series of pseudopeptides containing alkyl-, cycloalkyl-, aryl-, and aralkyl
      substituted 1,3,8-triazaspiro[4.5]decan-4-one-3-acetic acids as amino acid
      surrogates to replace the Pro2-Pro3-Gly4-Phe5 section of the peptide bradykinin
      B2 receptor antagonist [Pro3, Phe5]HOE 140 (D-Arg0-Arg1-Pro2-Pro3-Gly4-Phe5-Ser6
      D-Tic7+ ++-Oic8-Arg9) were prepared. These psuedopeptides were examined in vitro
      for their B2 receptor affinities as well as for their ability to block bradykinin
      mediated actions in vivo. Two compounds in particular, NPC 18521 (I) and NPC
      18688 (V) were quite potent in these latter assays, indicating that a significant
      portion of this prototypical second generation decapeptide antagonist can be
      replaced with a more compact nonpeptide molecule.

PMID- 8759639
TI  - Synthesis and biological activity of NK-1 selective, N-backbone cyclic analogs of
      the C-terminal hexapeptide of substance P.
AB  - The application of the concept of backbone cyclization to linear substance P (SP)
      analogs is presented. We describe the synthesis, characterization, and biological
      activity of a series of backbone-to-amino-terminus cyclic analogs of the C
      terminal hexapeptide of SP. These analogs were designed on the basis of NMR data
      and molecular modeling of the selective NK-1 analog WS-septide (Ac[Arg6,Pro9]SP6
      11). A series of peptides with the general formula: cyclo[-CH2)m-NH-CO-(CH2)n-CO
      Arg-Phe-Phe-N-]-CH2-CO-Leu-Met-NH2 (n = 2, 3, 6 and m = 2, 3, 4) was synthesized
      by solid phase methodology using Fmoc chemistry for the main chain and Boc
      chemistry for the building units [Na-(omega-aminoalkyl)Gly] side chains.
      Cyclization was performed on the resin after removal of the Boc protecting group
      from the omega-aminoalkyl chain. Cyclic and precyclic analogs were compared. They
      were purified by HPLC and characterized by mass spectroscopy and NMR. Biological
      activity and selectivity to the NK-1 neurokinin receptor were found to depend on
      cyclization and the ring size: The most active and selective analog had a ring of
      20 atoms. This analog was found to have enhanced metabolic stability in various
      tissue preparation compared to WS-septide.

PMID- 8759640
TI  - Aryl 1-but-3-ynyl-4-phenyl-1,2,3,6-tetrahydropyridines as potential antipsychotic
      agents: synthesis and structure-activity relationships.
AB  - A novel series of aryl 1-but-3-ynyl-4-phenyl-1,2,3,6-tetrahydropyridines with
      dopaminergic activity is described. The structure-activity relationships of this
      series were studied by synthesis of analogs and evaluation of their affinities
      for the dopamine (DA) D2 receptor and inhibition of locomotor activity (LMA) in
      rodents. The basic amine, alkyne chain length, and aryl groups were varied.
      Compounds having a 4-phenyl-1,2,3,6-tetrahydropyridine and an aryl group with
      hydrogen-bonding substituents separated by a butynyl chain were found to have the
      most potent dopaminergic activity. Several compounds that were found to have
      exceptional in vivo activity in LMA inhibition in rodents were evaluated for
      additional pharmacological activity including binding affinities for other DA
      receptor subtypes as well as effects on brain DA synthesis, DA neuronal firing,
      and conditioned avoidance responding in squirrel monkeys.

PMID- 8759641
TI  - A new highly selective metabotropic excitatory amino acid agonist: 2-amino-4-(3
      hydroxy-5-methylisoxazol-4-yl)butyric acid.
AB  - The homologous series of acidic amino acids, ranging from aspartic acid (1) to 2
      aminosuberic acid (5), and the corresponding series of 3-isoxazolol bioisosteres
      of these amino acids, ranging from (RS)-2-amino-2-(3-hydroxy-5-methylisoxazol-4
      yl)acetic acid (AMAA, 6) to (RS)-2-amino-6-(3-hydroxy-5-methylisoxazol-4
      yl)hexanoic acid (10), were tested as ligands for metabotropic excitatory amino
      acid receptors (mGlu1 alpha, mGlu2, mGlu4a, and mGlu6). Whereas AMAA (6) and (RS)
      2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propinoic acid (AMPA, 7) are potent
      and highly selective agonists at N-methyl-D-aspartic acid (NMDA) and AMPA
      receptors, respectively, the higher homologue of AMPA (7), (RS)-2-amino-4-(3
      hydroxy-5-methylisoxazol-4-yl)butyric acid (homo-AMPA, 8), is inactive at
      ionotropic excitatory amino acid receptors. Homo-AMPA (8), which is a 3
      isoxazolol bioisostere of 2-aminoadipic acid (3), was, however, shown to be a
      specific and rather potent agonist at mGlu6, approximately 4 times weaker than
      the nonselective excitatory amino acid receptor agonist (S)-glutamic acid. 2
      Aminoadipic acid (3), which shows a complex excitatory amino acid synaptic
      pharmacology, was an agonist at mGlu6 as well as mGlu2. AMPA (7) and the higher
      homologue of homo-AMPA (8), (RS)-2-amino-5-(3-hydroxy-5-methylisoxazol-4
      yl)pentanoic acid (9), showed relatively weak agonist effects at mGlu6. It is
      concluded that homo-AMPA (8) is likely to be a useful tool for studies of the
      pharmacology and physiological role of mGlu6. We describe a new versatile
      synthesis of this homologue of AMPA and the synthesis of compound 10.

PMID- 8759642
TI  - 1-aryl-4-[(1-tetralinyl)alkyl]piperazines: alkylamido and alkylamino derivatives.
      Synthesis, 5-HT1A receptor affinity, and selectivity. 3.
AB  - The synthesis and binding profile on 5-HT1A, 5-HT2, D-1, D-2, alpha 1, and alpha
      2 receptors of the N-4 long-chain arylpiperazines 22-40 are reported, where an
      amino or amido function is inserted into the intermediate chain linked to the
      alpha position of the tetralin nucleus. Unlike the buspirone analogues, for the
      amido derivatives studied in this paper, the terminal amide function of long
      chain piperazines is not important for 5-HT1A receptor affinity binding, and its
      removal yields high-affinity 5-HT1A receptor agents.

PMID- 8759643
TI  - Aza-peptide analogs as potent human immunodeficiency virus type-1 protease
      inhibitors with oral bioavailability.
AB  - A series of aza-peptide analogs with a (hydroxyethyl)hydrazine isostere has been
      synthesized as HIV-1 protease inhibitors using a simple synthetic scheme.
      Structure-activity studies based on the X-ray of a previously described inhibitor
      enzyme complex led to potent inhibitors with antiviral activity in the low
      nanomolar range. The S-configuration of the transition-state hydroxyl group was
      preferred in this series. Small modifications of the P2P3 and P2'P3' substituents
      had little effect on enzyme inhibition but greatly influenced the pharmacokinetic
      profile. As a result of these studies, the symmetrically acylated compound 8a and
      its close analog 24a bearing a methyl carbamate in P3 and an ethyl carbamate in
      P3' position were identified as potent inhibitors with plasma concentrations
      exceeding antiviral ED50 values 150-fold following oral application in mice.

PMID- 8759644
TI  - Synthesis and biological evaluation of certain alkenyldiarylmethanes as anti-HIV
      1 agents which act as non-nucleoside reverse transcriptase inhibitors.
AB  - Several novel alkenyldiarylmethane (ADAM) non-nucleoside HIV-1 reverse
      transcriptase inhibitors were synthesized. The most potent of these proved to be
      3',3"-dibromo-4',4"-dimethoxy-5'5"-bis(methoxycarbonyl)-1,1-diphenyl-1-+
      ++heptene (8) ADAM 8 inhibited the cytopathic effect of HIV-1 in CEM cell culture
      with an EC50 value of 7.1 microM and was active against an array of laboratory
      strains of HIV-1 in CEM-SS and MT-4 cells, but was inactive as an inhibitor of
      HIV-2. In common with the other known non-nucleoside reverse transcriptase
      inhibitors, ADAM 8 was an effective inhibitor of HIV-1 reverse transcriptase
      (IC50 1 microM) with poly(rC).oligo(dG), but not with poly(rA).oligo(dT), as the
      template/primer. ADAM 8 was inactive against HIV-1 reverse transcriptases
      containing non-nucleoside reverse transcriptase inhibitor resistance mutations at
      residues 101, 106, 108, 139, 181, 188, and 236, while it remained active against
      enzymes with mutations at residues 74, 98, 100, 103, and at 103/181. An AZT
      resistant virus having four mutations in reverse transcriptase was more sensitive
      to inhibition by ADAM 8 than the wild-type HIV-1. In addition, ADAM 8 displayed
      synergistic activity with AZT, but lacked synergy with ddI. ADAM 8 or a
      structurally related analog may therefore be useful as an antiviral agent in
      combination with AZT or with other NNRTIs that are made ineffective by mutations
      at residues which do not confer resistance to ADAM 8.

PMID- 8759645
TI  - Outpatient therapeutic ERCP: cutting sphincters and cutting costs.

PMID- 8759646
TI  - Wire-guided dilatation and fluoroscopy: is seeing believing?

PMID- 8759647
TI  - Cost-effectiveness: definitions and use in the gastroenterology literature.
AB  - In this era of rapid change in our health care system, we will be required to
      demonstrate that our practices and procedures in gastroenterology are both
      effective and cost-effective. In the face of rising national health care
      expenditures, the medical profession confronts an increased demand to justify
      practices and to demonstrate the value of its services. This has led to both an
      expansive literature examining the cost-effectiveness of practices and procedures
      and an alarming disparity in the definition and use of the term "cost
      effectiveness." Many reports may be lacking appropriate documentation of costs
      and benefits, the critical components for the determination of cost
      effectiveness. OBJECTIVE: The purpose of this article was to define what is meant
      by a "cost-effective" intervention, with special reference to gastroenterology.
      METHODS: The varied use of the term "cost-effective" in the gastroenterology
      literature is illustrated. Accepted definitions of the term are provided, and
      suggested uses are outlined. The value judgements that must be made in funding
      decisions are presented, and the parameters that may be used to determine the
      cost-effectiveness of a procedure or practice are discussed. SUMMARY: Cost
      effectiveness as it applies to GI medicine is defined, and appropriate and
      inappropriate uses of the term are illustrated. It is only through effective
      communication and precise definitions that we will be able to determine the cost
      effectiveness of our practices in gastroenterology.

PMID- 8759648
TI  - Zenker's diverticulum: reappraisal.
AB  - For more than 2 centuries, the nature and pathophysiology of pharyngoesophageal
      (Zenker's) diverticulum has been a matter of argument. The intrinsic or extrinsic
      forces and structures that might play a role in the development of this disorder
      have been repeatedly scrutinized, and still today the different theories of
      muscular incoordination and/or spasm, cricopharyngeal achalasia, gastroesophageal
      reflux, or neuromuscular abnormalities try to find their way as the final word
      regarding etiology remains to be told. Options for treatment follow a similar
      pattern although myotomy and diverticulopexy seem to have yielded the best
      results. In this review, historical and current data gathered from the world
      literature are compiled in an attempt to give a clear overview of the
      pathophysiology surrounding the genesis of Zenker's diverticulum and the clinical
      manifestations, diagnosis, and different alternatives for definite treatment of
      this disorder.

PMID- 8759649
TI  - A prospective study of the safety of endoscopic therapy for choledocholithiasis
      in an outpatient population.
AB  - OBJECTIVE: Many centers routinely admit patients for observation after endoscopic
      therapy of choledocholithiasis although this is contrary to the current mandate
      for cost containment. The purpose of this study was to determine the safety,
      success, and complication rates of outpatient therapeutic ERCP in the management
      of choledocholithiasis. METHODS: Over a 4-month period, 97 consecutive
      outpatients undergoing endoscopic treatment for choledocholithiasis were enrolled
      in a prospective manner. Each subject was observed 1-3 h postprocedure before
      discharge with follow-up at 10 days. RESULTS: Successful endoscopic management of
      choledocholithiasis was achieved in 100% of patients. Complication rates were as
      follows: pancreatitis (2.1%), postsphincterotomy bleeding (3.2%), perforation
      (0%), and sepsis (0%). One patient required admission during the observation
      period, and two others with pancreatitis were readmitted within 24 h of
      discharge. There was no apparent adverse clinical outcome related to this policy.
      CONCLUSION: Endoscopic therapy of choledocholithiasis may be performed safely on
      an outpatient basis, realizing significant cost savings.

PMID- 8759650
TI  - Esophageal dilation with polyvinyl (American) dilators over a marked guidewire:
      practice and safety at one center over a 5-yr period.
AB  - OBJECTIVE: Improvements in dilator technology over the past decade have
      revolutionized esophageal dilation. There remains, however, a number of
      controversies relating to several technical aspects of wire-guided dilation,
      including whether or not fluoroscopy is necessary. We describe our experience
      with wire-guided esophageal bougienage. METHODS: We retrospectively reviewed our
      experience with esophageal dilation using polyvinyl (American) dilators and
      marked guidewires over the period 1990-1994 to assess the practice habits of our
      endoscopists and the safety of the technique. We did 606 wire-guided dilations on
      354 adult patients. Dilations were done by six different endoscopists. RESULTS:
      Fluoroscopy was used in only 32/606 dilations (5.3%) and then only to pass a
      guidewire when the scope could not be passed through the stricture. Fluoroscopy
      was not used to monitor dilator passage. Peptic strictures were dilated to their
      maximal target size (determined by the individual endoscopist) in one session in
      195 of 253 instances (77.1%). Practice differences were seen between the
      individual endoscopists relating to how rapidly dilation was accomplished, the
      number of dilators passed per session, and the maximal dilator size passed. No
      perforations or other serious complications occurred in our series. CONCLUSIONS:
      Wire-guided esophageal bougienage is a very safe procedure when careful attention
      to technique is observed. No perforations were seen in our series of over 600
      dilations. Fluoroscopy is needed only in those cases in which a scope cannot be
      passed through a stricture to assist with guidewire passage. In a majority of
      cases, peptic strictures can be dilated to a 45-to 51-Fr size in a single
      session.

PMID- 8759651
TI  - The prevalence and clinical characteristics of short segments of specialized
      intestinal metaplasia in the distal esophagus on routine endoscopy.
AB  - OBJECTIVE: To prospectively determine the prevalence and clinical characteristics
      of short segments of specialized intestinal metaplasia in the distal esophagus.
      Short segment is defined as extending less than 2 cm proximal to the
      esophagogastric junction. This has been referred to by some investigators as
      "short segment Barrett's esophagus." METHODS: One hundred and seventy two
      patients undergoing elective esophagogastroduodenoscopy were consecutively
      enrolled. Patients with known Barrett's esophagus were excluded. All study
      patients completed a symptom questionnaire. At endoscopy, the presence of
      esophagitis and locations of the diaphragmatic hiatus, esophagogastric junction,
      and the squamocolumnar junction were recorded. Biopsy specimens were obtained at
      the squamocolumnar junction to identify specialized intestinal metaplasia and 2
      cm above the squamocolumnar junction to evaluate for histological esophagitis.
      RESULTS: Two patients (1.2%) had at least 2 cm of columnar-lined esophagus. Of
      the 170 patients without 2 cm of columnar-lined esophagus, 16 (9.4%) patients had
      short segments of specialized intestinal metaplasia. Twelve (7.0%) of these
      patients had specialized intestinal metaplasia limited to the esophagogastric
      junction. All patients with specialized intestinal metaplasia were Caucasian, and
      there was a slight male predominance. Patients without specialized intestinal
      metaplasia (n = 154, 90.6%) did not differ statistically with respect to age,
      gender, use of acid-suppressing drugs, alcohol, or smoking history. Pyrosis and
      regurgitation were significantly more common in patients with specialized
      intestinal metaplasia involving the distal 2 cm of the esophagus or the
      esophagogastric junction. Cough was more common in the group with specialized
      intestinal metaplasia limited to the esophagogastric junction. The groups were
      similar in frequency of dysphagia, globus sensation, nocturnal pyrosis,
      eructation, early satiety, nausea, and abdominal pain. CONCLUSIONS: Specialized
      intestinal metaplasia less than 2 cm proximal to the esophagogastric junction is
      common in Caucasian patients undergoing routine esophagogastroduodenoscopy.
      Pyrosis and regurgitation are significantly more common in patients with short
      segments of specialized intestinal metaplasia, whether involving the distal 2 cm
      of the esophagus or the esophagogastric junction alone. Alcohol and tobacco use
      are no more common in patients with specialized intestinal metaplasia than in
      those without metaplasia. The presence of specialized intestinal metaplasia did
      not correlate with either endoscopic or histological esophagitis.

PMID- 8759652
TI  - Antineutrophil cytoplasmic antibodies in relatives of patients with inflammatory
      bowel disease.
AB  - BACKGROUND: The occurrence of antineutrophil cytoplasmic antibodies (ANCA) has
      been reported more frequently than expected in healthy first-degree relatives of
      patients with ulcerative colitis, suggesting that these antibodies may represent
      a subclinical marker of genetic disease susceptibility. AIM: To determine the
      prevalence of ANCA in unaffected first-degree relatives of inflammatory bowel
      disease patients in a Spanish population. METHODS: Three hundred and seventy sera
      obtained from 80 patients with inflammatory bowel disease (55 ulcerative colitis,
      25 Crohn's disease), 217 unaffected first-degree relatives (157 from ulcerative
      colitis and 60 from Crohn's disease patients), 62 healthy controls, and 11 celiac
      disease patients were tested using an indirect immunofluorescence assay. RESULTS:
      Antibodies were detected in 64% of patients with ulcerative colitis but in only
      12.5% of patients with Crohn's disease. ANCA were seldom present in their
      unaffected first-degree relatives (4.6%), control subjects (1.6%), and celiac
      disease patients (0%). CONCLUSIONS: In the Spanish population studied,
      antineutrophil cytoplasmic antibodies occur more commonly in ulcerative colitis
      than in Crohn's disease, as reported in other Caucasian populations. Moreover,
      their presence is not increased in their first-degree relatives. These findings
      indicate that ANCA are not a subclinical marker of genetic susceptibility to
      inflammatory bowel disease in this population.

PMID- 8759653
TI  - Evaluation of liver histology, ALT elevation, and HCV RNA titer in patients with
      chronic hepatitis C.
AB  - OBJECTIVE: Hepatic histological evaluation is currently the gold standard to
      determine the degree of liver injury in chronic hepatitis C. It is unclear
      whether degree of serum ALT elevation or quantitative hepatitis C virus (HCV) RNA
      can predict level of histological damage. METHODS: Fifty nine biopsies from 44
      patients with chronic hepatitis C were reviewed. The amount of liver damage was
      quantified using the Histology Activity Index (HAI) and was compared with serum
      ALT and, in 26 biopsies, quantitative HCV RNA (branched DNA amplification,
      Quantiplex, Chiron). RESULTS: A statistically significant linear relationship was
      noted between degree of ALT elevation and amount of liver injury based on HAI
      score (p < 0.05) although this relationship was not statistically strong (rs =
      0.4900). No significant correlation was noted between serum ALT and HCV RNA titer
      (rs = 0.4044) or between quantitative HCV RNA titer and HAI score (rs = 0.3506).
      No individual component of the HAI correlated with ALT or HCV RNA. CONCLUSIONS:
      Although there is a correlation between serum ALT and degree of hepatic injury
      based on HAI score, this relationship is weak and probably of no clinical use.
      There is no significant correlation between HCV RNA and serum ALT or HCV RNA and
      degree of hepatic injury in individual patients. Hepatic histological evaluation
      continues to be required for clinical assessment of patients with chronic
      hepatitis C.

PMID- 8759654
TI  - alpha-Interferon retreatment of patients with chronic hepatitis C.
AB  - To evaluate the effect of a second cycle of alpha-IFN treatment on patients who
      have not responded to a first cycle or responded and relapsed, 37 patients, 25
      men and 12 women, mean age 41 yr, were retreated with alpha-interferon (IFN).
      Seven patients responded to the first cycle of treatment, and 30 did not. Five
      patients who had not responded to the second cycle received a third one. All
      patients received twice the dose of the first cycle unless they experienced side
      effects during the first cycle. Thus, nine patients received 9 mU/w, nine
      received 15 mU/w, and 19 received 30 mU/w for 6 months. Complete response was
      defined as nondetectable hepatic hepatitis C virus (HCV)-RNA at the end of
      therapy; sustained response was defined as normal ALT levels with negative serum
      HCV-RNA at > 6 months after cessation of therapy. Of the 30 nonresponders to the
      first cycle, eight responded to the second, but only four (13%) had a sustained
      response. Six of the seven responders to the first cycle responded to the second
      cycle, but only three had a sustained response (3/7, 43%) (p = NS). Although 33
      and 21% (p = NS) of those who were treated with 15 mU/w and 30 mU/w,
      respectively, showed a sustained response, none of those treated with 9 mU/w had
      a sustained response (p = NS). Although age or sex of the patients studied had no
      effect on the response rate, liver histology was an important factor because only
      noncirrhotics showed a long term response (47 vs 0%; p < 0.02). There was no
      difference in response rate between patients with chronic active hepatitis and
      chronic persistent hepatitis. In conclusion, noncirrhotic patients who have not
      responded or responded and relapsed to a 6-month course of alpha-INF (3-5 mU
      three times per week) should try a second course at a dose of 15 mU/w.
      Retreatment may induce complete and long lasting response in 13% of the initial
      nonresponders and 43% of the initial responders. A second course of alpha-IFN in
      nonresponding cirrhotics appears ineffective in clearing the virus at the doses
      used.

PMID- 8759655
TI  - Persistent acid secretion during omeprazole therapy: a study of gastric acid
      profiles in patients demonstrating failure of omeprazole therapy.
AB  - OBJECTIVE: To identify patients with gastroesophageal reflux disease (GERD) who,
      despite omeprazole 20 mg b.i.d., demonstrate continued abnormal gastric acid
      secretion. METHODS: Eighty-eight patients with GERD completed ambulatory gastric
      and esophageal pH monitoring for persistent symptoms on omeprazole 20 mg b.i.d..
      Seventeen (19%) demonstrated abnormal gastric acid secretion (percentage time
      gastric pH < 4 > 50%). The 17 omeprazole failures (OF) were compared with: 1) 19
      randomly selected patients with GERD (also studied on omeprazole 20 mg b.i.d. and
      2) 19 normal volunteers studied on both placebo and omeprazole 20 mg b.i.d..
      Total time intragastric pH < 4, 24-hr gastric pH frequency distribution, and 15
      min median pH values for the 6-h period after the evening omeprazole dose were
      compared. RESULTS: Both the 24-hr frequency distribution for gastric pH and the
      15-min median gastric pH profile for patients with GERD and volunteers on
      omeprazole 20 mg b.i.d. were almost identical. By contrast, gastric pH studies
      from the OF group receiving omeprazole 20 mg b.i.d. most closely resembled those
      of the normal subjects receiving placebo, with respect to these variables.
      Gastric pH monitoring in seven of the 17 OF patients while on omeprazole 80
      mg/day demonstrated a significant decrease in the median percentage time gastric
      pH remained below 4 (32.8% on 80 mg/day vs 74.3% on 40 mg/day; p < 0.02).
      CONCLUSION: There are individuals whose intragastric acidity persists despite
      conventional doses of omeprazole. Although the underlying mechanism remains
      unclear, the majority (six of seven) (87%) demonstrated improved gastric acid
      control when placed on high dose omeprazole, indicating that this is often a dose
      dependent phenomenon.

PMID- 8759656
TI  - Optimal dosing of omeprazole 40 mg daily: effects on gastric and esophageal pH
      and serum gastrin in healthy controls.
AB  - BACKGROUND: Little is known about the best regimen of omeprazole 40 mg/day for
      suppressing gastric acid and distal esophageal acid exposure. In addition, the
      relationship between the level of serum gastrin and gastric pH and this therapy
      is still uncertain. METHODS: Nineteen healthy male volunteers (mean age 25 yr)
      had a baseline fasting serum gastrin and 24-h ambulatory combined distal
      esophageal and gastric pH monitoring. Subjects underwent a 7-day course of each
      of three specific regimens of omeprazole 40 mg (20 mg b.i.d., 40 mg qAM, 40 mg
      qPM) with repeat pH and gastrin on day 6. Meals and activity patterns were
      constant for each subject during the test series. Medications were taken before
      meals. RESULTS: All dosing regimens caused significant (p < 0.01) acid reduction
      compared with baseline in both the stomach and the distal esophagus. There was no
      significant difference in the amount of acid exposure (time pH < 4) among the
      three dosing regimens in the esophagus and between qAM and qAM dosing in the
      stomach. However, b.i.d. dosing gave better (p < 0.05) gastric acid suppression
      compared with single daily dosing in 15 of 19 subjects. When the baseline was
      compared with all regimens of omeprazole 40 mg, there was a significant
      difference with both the serum gastrin (p < 0.01) and the percentage time gastric
      pH was < 4 (p < 0.01). The correlation between change in serum gastrin and change
      in percentage time gastric pH was < 4 was poor (r = 0.26). CONCLUSIONS: Divided
      dosing of omeprazole 20 mg b.i.d. provides superior gastric acid suppression to
      either once a day regimen of omeprazole 40 mg in most individuals. Serum gastrin
      levels do not correspond well to gastric pH, necessitating the use of gastric pH
      monitoring to accurately determine the response to gastric acid suppression.

PMID- 8759657
TI  - The prevalence of esophagitis in patients with duodenal ulcer or ulcer-like
      dyspepsia.
AB  - OBJECTIVE: It has been reported that 30-72% of patients with duodenal ulcer
      disease also have esophagitis. However, many of these reports included patients
      who had severe or complicated ulcer disease, so that the high prevalence may
      reflect pyloric stenosis or gastric hyper-secretion. The objective of this study
      was to determine the prevalence of esophagitis in unselected patients with
      duodenal ulcer disease or ulcer-like dyspepsia. METHOD: A prospective study of
      endoscopic and histological esophagitis in consecutive patients with either
      duodenal ulcer disease or with ulcer-like dyspepsia. RESULTS: Of 27 patients with
      duodenal ulcer disease, 33% had endoscopic esophagitis, 26% had histological
      esophagitis, and 48% had esophagitis by either criterion. Of 66 patients with
      ulcer-like dyspepsia, 35% had endoscopic esophagitis, 47% had histological
      esophagitis, and 62% had esophagitis by either criterion. Esophagitis was
      independent of patients' Helicobacter pylori status. CONCLUSIONS: Esophagitis is
      common in patients with duodenal ulcer disease, and the prevalence is similar in
      patients with ulcer-like dyspepsia. In addition to causing heartburn, esophagitis
      may also be cause ulcer-like epigastric pain. Concomitant esophagitis may account
      for the persisting or recurring dyspepsia that has been reported in up to one
      third of duodenal ulcer patients after successful eradication of H. pylori.

PMID- 8759658
TI  - Differences between generalist and specialist physicians regarding Helicobacter
      pylori and peptic ulcer disease.
AB  - OBJECTIVES: To assess differences between gastroenterologists and primary care
      physicians in the United States in their attitudes, timing of adoption, and
      practice patterns concerning the use of Helicobacter pylori eradication therapy
      in peptic ulcer disease (PUD) patients. METHODS: We surveyed a random sample of
      4500 gastroenterologists, family practitioners, and general internists shortly
      after a National Institutes of Health Consensus Conference recommended
      eradication of H. pylori in PUD patients. RESULTS: The survey response rate was
      30%. Bivariate comparisons revealed significant differences between primary care
      physicians and gastroenterologists in sources of information about H. pylori,
      beliefs about the strength of the evidence supporting the relationship between H.
      pylori and PUD, adoption of H. pylori eradication therapy and timing of first
      use, and patients likely to receive eradication therapy. Although adoption of H.
      pylori eradication therapy was nearly universal among gastroenterologists by
      April 1994 (99%), approximately one-third of primary care providers had never
      prescribed H. pylori eradication therapy. Practice patterns of physicians using
      eradication therapy also varied significantly by specialty group. CONCLUSIONS:
      Gastroenterologists were more aware of the relationship of H. pylori to PUD and
      adapted their practices more quickly to this emerging information than did
      primary care providers. Specialty differences in attitudes and adoption patterns
      of medical innovation existed, even when the new intervention did not require
      specialized training or equipment. These findings have important clinical
      implications as the role of primary care physicians expands and managed care
      delivery systems decrease the use of specialist services.

PMID- 8759659
TI  - Antimicrobial therapy for Helicobacter pylori infection versus long-term
      maintenance antisecretion treatment in the prevention of recurrent hemorrhage
      from peptic ulcer: prospective nonrandomized trial on 125 patients.
AB  - OBJECTIVE: Our objective was to assess the effectiveness of therapy for
      Helicobacter pylori (HP) on the prevention of recurrent bleeding in patients with
      recent upper gastrointestinal hemorrhage from peptic ulcers. METHODS: We
      performed a prospective follow-up study without randomization on 125 consecutive
      patients (83 males and 42 females) who had presented with their first major
      episode of upper gastrointestinal hemorrhage from peptic ulcer (22 gastric and
      103 duodenal ulcers). All 125 patients were HP-positive. During the acute phase
      of bleeding, all patients were treated with standard supportive measures. After
      the acute bleeding phase, patients were allocated to two treatment groups: 1)
      antimicrobial therapy-84 patients received one of the following three regimens:
      1) amoxicillin 500 mg t.i.d. for 10 days + omeprazole 20 mg b.i.d. for 30 days;
      2) clarythromycin 500 mg t.i.d. for 12 days + omeprazole 20 mg b.i.d. for 30
      days; or 3) amoxicillin 500 mg t.i.d. for 10 days + metronidazole 500 mg t.i.d.
      for 10 days + colloidal bismuth subcitrate 240 mg b.i.d. for 30 days. For long
      term antisecretion maintenance treatment, 41 patients were allocated to either
      omeprazole 20 mg once a day or ranitidine 150 mg once a day, for 1 yr. RESULTS:
      During the follow-up period, peptic ulcers recurred in six patients in the
      antibiotic group (7.14%) and 13 patients in the maintenance group (31.7%) (p <
      0.001). The fraction of patients without recurrent bleeding was greater in the
      antibiotic group than in the maintenance group. Two patients in the antibiotic
      group (2.3%) and five in the maintenance group (12.1%) had recurrent hemorrhages
      (p < 0.1). CONCLUSION: Cure of HP infection reduces the recurrence of peptic
      ulcer and of rebleeding from ulcer disease more effectively than does long-term
      maintenance therapy.

PMID- 8759660
TI  - Early recognition of post-ERCP pancreatitis by clinical assessment and serum
      pancreatic enzymes.
AB  - BACKGROUND: This study evaluates the relative value of clinical assessment and
      serum pancreatic enzymes in the discharge management of outpatients undergoing
      ERCP. METHODS: Two hundred thirty-one patients who underwent ERCP had a detailed
      clinical assessment performed 2 h after the procedure and blood drawn for amylase
      and lipase. RESULTS: One-third of the patients who later developed pancreatitis
      had no pain 2 h after the end of the procedure, whereas an equal number who had
      no pancreatitis did complain of pain. Values below 276 U/L for amylase and 1000
      U/L for lipase were useful in ruling out pancreatitis with negative predictive
      values of 0.97 and 0.98, respectively. Based on the data of this study a
      discharge algorithm for outpatients undergoing ERCP is proposed. CONCLUSIONS: In
      contrast to clinical assessment, which is unreliable, it is possible to stratify
      patients according to their risk of developing pancreatitis according to their 2
      h serum amylase and lipase values. This helps to rationalize the discharge
      management of outpatients undergoing ERCP at a time when careful utilization of
      resources, especially the avoidance of unnecessary hospital admissions, becomes
      increasingly more important.

PMID- 8759662
TI  - Survival of patients diagnosed with colorectal cancer through a television
      advertised screening program.
AB  - OBJECTIVES: Although controversial, fecal occult blood testing (FOBT) is
      advocated to reduce mortality due to colorectal cancer. Our aim was to determine
      whether a television-advertised screening program for colorectal cancer using
      fecal occult blood tests improved survival of patients diagnosed with colorectal
      cancer. METHODS: A retrospective analysis of the stage and survival of patients
      diagnosed with colorectal cancer in our 1986 and 1987 screening programs was
      conducted. The 5-yr survival rate of patients diagnosed with colorectal cancer
      was determined in our screened population and compared with national survival
      data from the National Cancer Institute Surveillance, Epidemiology, End Results
      (SEER) program. RESULTS: In our screening programs, 75,633 FOBT were distributed
      and returned for analysis. Test slides were positive in 3.3%. Follow-up was
      available in 121 of 131 patients diagnosed with colorectal cancer. In our
      screened population, significantly more colorectal cancers were identified in a
      localized stage compared with the national average (76 vs 37%). Consequently, the
      percentage of our patients with regional and distant disease was decreased
      compared with SEER data. The overall 5-yr survival rate of patients with
      colorectal cancer who participated in our screening program was significantly
      higher than the national survival rate (75 vs 59%). Survival of patients older
      than 75 yr of age with colorectal cancer in our screening program was not
      improved. CONCLUSIONS: Television-advertised screening for colorectal cancer
      using FOBT was effective in recruiting a large number of participants. Patients
      diagnosed with colorectal cancer in our program tended to have early stage
      disease with improved 5-yr survival. The results of this study support FOBT as an
      effective means to reduce the mortality of colorectal cancer.

PMID- 8759661
TI  - Antioxidants in hereditary pancreatitis.
AB  - OBJECTIVE: The cause of hereditary pancreatitis (HP) remains unknown. This study
      evaluated the hypothesis that patients with HP have genetically determined low
      concentrations of antioxidants that may predispose them to repetitive pancreatic
      injury. METHODS: This cross-sectional analysis compared antioxidant levels in
      four groups of patients. Group 1 included 14 related people with chronic
      pancreatitis. Group 2 (11 individuals) belonged to the same kindred but did not
      have pancreatitis. Group 3 was a group of 65 unrelated control subjects, and
      Group 4 consisted of seven unrelated children with chronic pancreatitis from
      other causes. The antioxidant levels analyzed included glutathione peroxidase,
      superoxide dismutase, glutathione reductase, glutathione transferase, selenium,
      and vitamin E. Amylase levels were measured in all patients in groups 1, 2, and
      4. RESULTS: People with chronic pancreatitis or relatives of people with
      hereditary pancreatitis (groups 1, 2, and 4) had significantly lower mean
      glutathione peroxidase values than controls (group 3, p < 0.001). Group 1 also
      had significantly lower selenium levels than groups 2 and 3 (p < 0.001) but
      greater levels than group 4 (p = 0.029). Vitamin E levels were lower in group 1
      than in groups 2 and 4. The superoxide dismutase levels were significantly
      different between each group (p < 0.001), and group 1 had the highest level. The
      glutathione reductase, glutathione transferase, and amylase levels did not differ
      significantly between groups. However, group 1 had a significantly higher
      glutathione transferase level than group 4. CONCLUSION: We identified antioxidant
      deficiencies in a group of patients with hereditary pancreatitis. Higher selenium
      and vitamin E levels may have prevented their relatives in group 2 from having
      pancreatitis secondary to oxidant injury, despite low glutathione peroxidase
      levels. Supplementation with selenium or vitamin E or both may be a beneficial
      therapeutic option in these patients to decrease the frequency of pancreatitis.

PMID- 8759663
TI  - Changes in overnight fasting intragastric pH show poor correlation with
      duodenogastric bile reflux in normal subjects.
AB  - BACKGROUND: Spontaneous rises in intragastric pH are a common phenomenon in
      patients and normal subjects who undergo prolonged ambulatory pH monitoring;
      however, controversy exists over their etiology. Some investigators have
      postulated that these events are secondary to duodenogastric bile reflux (DGBR),
      and others have implicated increased salivation or increased esophageal
      bicarbonate production. The advent of a fiberoptic system that reliably
      identifies the presence of bilirubin has made it feasible to qualitatively detect
      DGBR. We used this technology along with simultaneous ambulatory intragastric pH
      monitoring to evaluate the relationship between DGBR and rises in intragastric pH
      in normal subjects. METHODS: We studied five normal subjects for a 15-h overnight
      period with simultaneous intragastric pH and bilirubin monitoring. The probes
      were sutured together so that the pH electrode lay adjacent to the fiberoptic
      bilirubin sensor, then passed transnasally into the fundus of the stomach.
      Subjects were fasted for the entire study. Data were obtained by plotting all
      intragastric pH values (recorded every 4 s) and their corresponding intragastric
      bilirubin absorbance units (recorded every 8 s) at 5-min intervals from the
      beginning to the end of the study for each of the five subjects (n = 903).
      RESULTS: Regression analysis of the data showed poor correlation (r = 0.26)
      between intragastric pH and intragastric bilirubin absorbance. CONCLUSION: Rises
      in intragastric pH do not predict the presence of bile in normal subjects. In
      addition, DGBR usually does not cause alkaline shifts of intragastric pH.
      Although further studies are needed to fully elucidate the etiology of
      spontaneous rises in intragastric pH, we believe that the measurement of
      "alkaline reflux" with ambulatory intragastric pH monitoring alone is an outdated
      technique and that the Bilitec 2000 should become the standard technique for the
      detection of intraluminal bile.

PMID- 8759664
TI  - The Short Inflammatory Bowel Disease Questionnaire: a quality of life instrument
      for community physicians managing inflammatory bowel disease. CCRPT
      Investigators. Canadian Crohn's Relapse Prevention Trial.
AB  - OBJECTIVE: Health-related quality of life (HRQOL) affects outcome in chronic
      diseases such as inflammatory bowel disease (IBD). The inflammatory bowel disease
      questionnaire (IBDQ), a disease-specific HRQOL questionnaire, can define changes
      in health status in IBD, but simple instruments are needed for daily application.
      The present study proposed to develop a short version of the IBDQ, the SIBDQ, for
      community physicians. METHODS: Using data from a clinical trial in 149 patients
      with Crohn's disease, 10 items were selected (by forward stepwise regression)
      that best explained the variance of the IBDQ or dimensional scores (bowel,
      systemic, social, emotional). The validity, reliability, and responsiveness of
      the SIBDQ were then assessed in 150 different patients with Crohn's disease and
      45 with ulcerative colitis. All scores were reported with a 7-point scale (1 =
      poor HRQOL, 7 = optimum HRQOL). RESULTS: Mean SIBDQ scores were similar (p =
      0.22) in Crohn's patients among 14 participating centers at study entry. Mean
      scores were lower in active Crohn's disease (range 4.00-4.92) than inactive
      disease (range 4.67-5.83; p = 0.0015). In active ulcerative colitis, the mean
      SIBDQ was 4.79 +/- 1.17 compared to 5.90 +/- 0.80 (p = 0.0006) in inactive
      disease. The SIBDQ explained 92% and 90% of the IBDQ variance in Crohn's disease
      and ulcerative colitis, respectively. In patients with stable Crohn's disease,
      the test-retest reliability coefficient was 0.65 and Crohnbach's alpha was 0.78,
      indicating good reliability. In patients with Crohn's disease who relapsed during
      follow-up, the mean SIBDQ decreased by -0.93 + 0.55 (p = 0.001). CONCLUSION: The
      SIBDQ is valid, reliable, and able to detect meaningful clinical changes in HRQOL
      that might occur in the office setting.

PMID- 8759665
TI  - Treatment of irritable bowel syndrome with Lacteol Fort: a randomized, double
      blind, cross-over trial.
AB  - OBJECTIVE: To assess the efficacy of Lacteol Fort, an antidiarrheal drug, in
      patients suffering from the chronic intestinal disease known as irritable bowel
      syndrome (IBS). DESIGN: The randomized, double-blind, cross-over trial versus
      placebo was carried out from 1992 to 1994. This trial consisted of administering
      a 6-wk treatment with a first drug (Lacteol Fort or placebo), followed by a wash
      out period of 2 wk, and then the administration of a second drug for a further 6
      wk (placebo or Lacteol Fort). Among the 29 patients eligible after recruitment,
      18 adults with well documented IBS fulfilled the inclusion criteria. Four
      patients were dropped for loss of materials used in the study and seven for lack
      of compliance. The patient's initial state was assessed using a questionnaire
      relating to six criteria: abdominal pain, bloating or gas, daily number of
      stools, consistency, mucus content, and general physical state. During the
      treatment, these criteria were evaluated daily by the patients themselves.
      RESULTS: All investigated criteria were scored, and then a daily mean index was
      calculated. The statistical analysis of the daily mean index values showed that
      the number of patients (nine cases) obtaining better results with Lacteol Fort
      than with placebo was statistically significant (p = 0.018). CONCLUSIONS: This
      double-blind, placebo-controlled, cross-over trial demonstrated that Lacteol Fort
      leads to a statistically significant therapeutic benefit in 50% of patients, when
      taking into consideration all of the six selected clinical criteria considered
      representative of IBS.

PMID- 8759666
TI  - Preoperative diagnosis of mucinous gastric adenocarcinoma by endoscopic
      ultrasonography.
AB  - OBJECTIVES: The aims of this study were to investigate the characteristic
      features of mucinous gastric carcinoma on endoscopic ultrasonography (EUS) and to
      demonstrate the usefulness of EUS in the preoperative diagnosis of this disease.
      METHODS: Twelve patients with mucinous gastric carcinoma who underwent EUS
      examination between April 1984 and April 1995 were enrolled in this study. All
      patients subsequently underwent surgery. Histopathologically, tumors were
      classified according to the mucin content (high or moderate) and the glandular
      formation of the tumor cells (well or poorly differentiated). Finally, the
      histological and endosonographic features were compared. RESULTS: In all
      patients, the infiltrated wall appeared echogenic because of diffusely
      distributed, reticular, highly echoic speckles in the submucosa and muscularis
      propria. The presence of mucinous lakes surrounded by reactive fibrous tissue
      correlated well with reticular, highly echoic speckles on EUS. There was an
      increase in echogenicity and thickness of the muscularis propria, depending on
      the invasion of the mucin. Although the boundary between submucosa and muscularis
      propria was distinct and the five-layered gastric wall structure was generally
      preserved, the mucosal layer was not discriminated in patients with poorly
      differentiated mucinous carcinoma with high mucin content. CONCLUSIONS: As a
      preoperative diagnostic procedure, EUS may be useful in recognizing the mucinous
      component of gastric tumors and may facilitate the differentiation of mucinous
      carcinoma from other gastric epithelial tumors.

PMID- 8759667
TI  - Ultrasound-guided percutaneous transhepatic fine needle aspiration cytology study
      of gallbladder polypoid lesions.
AB  - OBJECTIVE: To determine the accuracy and safety of ultrasound (US)-guided
      percutaneous transhepatic fine needle aspiration cytology (PT FNAC) in the
      diagnosis of large gallbladder (GB) polyps, especially cholesterol polyps.
      METHODS: Between January 1993 and April 1995, 17 patients with GB polyps of a
      size over 1 cm were examined preoperatively with US-guided PT FNAC, with needle
      aspiration from the center of the polyps. A cytological-histopathological
      correlation study was performed postoperatively to assess the accuracy of the PT
      FNAC results. RESULTS: 1) All eight cholesterol polyps were accurately diagnosed
      with the PT FNAC alone, showing foamy histiocytes. 2) In five patients, a
      diagnosis of epithelial tumor was made with PT FNAC study, showing the presence
      of columnar epithelium, but the PT FNAC failed to detect focal malignant change
      in adenomas of three of these patients. Only one case of adenocarcinoma was
      correctly diagnosed preoperatively by the PT FNAC. 3) The PT FNAC failed to
      detect an inflammatory polyp in one patient. 4) Failed cytology study was
      encountered in three patients-only bile was aspirated out. One patient had a GB
      stone, misdiagnosed as a GB polyp, another had an adenomyoma, and the last
      patient had chronic cholecystitis with Rokitansky-Aschoff sinuses. 5) One
      complication occurred-mild bile peritonitis. CONCLUSIONS: US-guided PT FNAC
      directly targeting the GB lesions seems accurate in the diagnosis of cholesterol
      polyps, and is a safe procedure.

PMID- 8759668
TI  - Endoscopic features of gastric inflammatory fibroid polyps.
AB  - OBJECTIVES: The inflammatory fibroid polyp (IFP) is a rare benign lesion that can
      occur throughout the digestive tract. The aim of this study is to describe
      endoscopic features of gastric IFPs and to determine the clinical value of
      endoscopic removal. METHODS: Upper gastrointestinal endoscopy was performed in 13
      patients with gastric IFPs. The IFPs were resected either by endoscopic removal
      or gastrectomy, and confirmed histologically as IFPs. To evaluate the diagnostic
      value, endoscopic features of the lesions were analyzed. RESULTS: The most
      frequent features were semi-pedunculated protrusions (61.5%), covered with a
      smooth surface of normal mucosa (100%), and located in the antrum or prepyloric
      region (100%). Bridging folds were observed in three of the 13 lesions (23.1%).
      The central surface of all 10-mm or larger lesions had an erythematous depression
      (three lesions), ulceration (five lesions), or white cap on the polyp (one
      lesion). Endoscopic biopsies failed to confirm IFP in any lesions. CONCLUSIONS:
      IFPs are commonly visualized as semi-pedunculated elevations, covered with a
      smooth surface of normal mucosa, and located in the antrum or prepyloric region.
      The 10-mm or larger lesions have central changes. Endoscopic removal of gastric
      IFPs is a useful method for both accurate diagnosis and treatment in view of
      negative results with the use of standard biopsy forceps.

PMID- 8759669
TI  - The safety and efficacy of percutaneous endoscopic gastrostomy after recent
      myocardial infarction: a study of 28 patients and 40 controls at four university
      teaching hospitals.
AB  - OBJECTIVES: To analyze the risks versus benefits of percutaneous endoscopic
      gastrostomy (PEG) performed soon after myocardial infarction. METHODS:
      Retrospective review of 28 patients undergoing PEG within 30 days after
      myocardial infarction at four university teaching hospitals for study periods of
      up to 10 yr. Forty controls undergoing PEG were matched for age and sex and had
      no myocardial infarction during the prior 6 months. RESULTS: Indications for PEG
      were inability to eat because of stroke in 13, chronic dependency on mechanically
      assisted ventilation in seven, anoxic encephalopathy in five, dementia in two,
      and other in one. The mean patient age was 72.5 +/- 9.2 (SD) yr. PEG was
      performed on average 22.3 +/- 6.2 days after myocardial infarction. Seventeen
      patients were intubated and were receiving mechanically assisted ventilation at
      the time of PEG. PEG was successfully performed in all patients. Study patients
      suffered two insignificant complications, and one significant complication from
      PEG of bleeding at the gastrostomy site that required transfusion of 4 U of
      packed erythrocytes. Of note, no study patient suffered a cardiovascular
      complication due to PEG. The control complication rate was not significantly
      different (three insignificant and one significant complications, NS, Fisher's
      exact test). PEG feedings in study patients resulted in stabilization of body
      weight and significant improvement of the serum albumin level (from 2.2 +/- 0.3
      gm/dl to 2.5 +/- 0.5 gm/dl, p < 0.03, Student's t test). Also the absolute
      lymphocyte count, hematocrit, and serum total protein level tended to improve
      after PEG. PEG contributed to transfer to a rehabilitation center, skilled
      nursing facility, or home in 19 study patients (70%; control rate = 78%, NS, chi
      2). CONCLUSION: Recent myocardial infarction is not an absolute contraindication
      to PEG. In this study, the benefits exceeded the risks of PEG in medically stable
      patients. PEG should be performed with monitoring by electrocardiography and
      pulse oximetry in medically stable patients. PEG is an elective procedure that
      should not be performed in highly unstable patients.

PMID- 8759670
TI  - Abdominal ultrasound in the assessment of extent and activity of Crohn's disease:
      clinical significance and implication of bowel wall thickening.
AB  - AIMS: The aim of this study was to evaluate the relevance of ultrasound (US) in
      assessing disease extent and activity in a series of patients with quiescent or
      active Crohn's disease (CD). In particular, the study was aimed at evaluating
      whether US may be useful in distinguishing between active disease and bowel wall
      thickening (BWT) due to fibrosis. PATIENTS AND METHODS: A series of consecutive
      patients with ileal, ileo-colonic, or colonic CD previously studied with x-ray
      and/or endoscopy, underwent abdominal US. The following parameters were also
      determined in these patients: CD activity index (CDAI), erythrocyte sedimentation
      rate, C reactive protein, length of disease, previous surgical resection, and
      number of recurrences. The relationship between BWT and the aforesaid parameters
      was assessed by means of univariate and multiple regression analysis. RESULTS:
      Overall sensitivity and specificity of US for the assessment of anatomical
      distribution of CD were 89% and 94%, respectively, and there was also a
      significant correlation between the extent of ileal disease measured by US and
      that determined by small bowel x-ray. By univariate analysis, statistically
      significant correlations were found between BWT, CDAI, and biological indices of
      inflammation (erythrocyte sedimentation rate and C reactive protein), although
      all the correlation coefficients were low with values not exceeding 0.40, and
      among these, backward multiple regression analysis identified only CDAI, along
      with ileo-colonic localization, as the subset of predictive variables of bowel
      wall thickness. However, both predictions were rather weak and accounted for only
      20% of the variability of the BWT. In addition, a significant relationship was
      found between disease US extent and clinical or biochemical disease activity.
      However, in a subgroup of patients characterized by quiescent disease and high
      BWT, CD was complicated by higher prevalence of strictures, as detected by
      radiological and endoscopic examinations, and more frequent surgical outcome than
      others. CONCLUSIONS: Abdominal US is an accurate method for determining the
      abdominal distribution of CD and appears to be accurate in detecting and
      evaluating the disease length of ileal lesions. In contrast, despite a weak but
      significant correlation between BWT and clinical and biochemical parameters, the
      usefulness of US as an index of disease activity seems to be fairly limited.
      However, a high BWT in quiescent patients suggests the presence of fibrosis,
      which is poorly responsive to steroid treatment.

PMID- 8759671
TI  - Intrahepatic metastases in hepatocellular carcinoma: evidence for spread via the
      portal vein as an efferent vessel.
AB  - BACKGROUND: The mechanism and pathogenesis of the high frequency of intrahepatic
      metastasis in hepatocellular carcinoma (HCC) has not yet been elucidated.
      METHODS: Two hundred thirty-one tumors ( < or = 5 cm in diameter) of resected
      specimens of HCC were examined for the relationship between mode of tumor spread
      and tumor size. Efferent vessels in HCC were identified by direct injection of
      radiopaque material into the tumor in 23 resected liver specimens selected from
      the 231 tumors. RESULTS: The most frequent site for tumor spread in HCC was
      capsular invasion followed by extracapsular invasion, vascular invasion, and
      finally intrahepatic metastasis. Radiopaque material injected directly into 23
      resected tumors entered the portal vein in only 17 tumors and entered into both
      the portal and hepatic veins in six tumors. CONCLUSIONS: These findings suggest
      that tumor spread in HCC progresses from capsular invasion to intrahepatic
      invasion and that the portal vein may act as an efferent tumor vessel.

PMID- 8759672
TI  - Diagnosis of pancreatic cancer by K-ras point mutation and cytology of pancreatic
      juice.
AB  - OBJECTIVES: Recently, it was reported that detection of K-ras point mutation at
      codon 12 in pancreatic juice is an objective method for the diagnosis of
      pancreatic cancer, but a few reports have suggested that this might represent an
      early event in pancreatic oncogenesis. In the present study we examined, in
      various patients, the occurrence of K-ras codon 12 point mutation in pancreatic
      juice and compared it with pancreatic juice cytology, which is also a reliable
      diagnostic method. METHODS: Pancreatic juice was obtained endoscopically from
      patients with various pancreatic disorders and those without definite diseases,
      and was examined cytologically and for the occurrence of K-ras codon 12 point
      mutation. The K-ras gene was amplified by polymerase chain reaction (PCR) and the
      mutation at codon 12 (GGT-->GAT) was examined by slot blot hybridization
      analysis. RESULTS: K-ras point mutation at codon 12 was detected in seven of 14
      (50%) pancreatic cancers, in four of 10 (40%) mucin-producing tumors, in four of
      13 (31%) chronic pancreatitis, and in two of 10 (20%) pancreas without definite
      disorders. K-ras point mutation was detected in nine of 18 (50%) pancreatic juice
      samples containing cancer cells, in eight of 18 (44%) pancreatic juice samples
      containing atypical cells, but in none of such samples containing only normal
      cells. CONCLUSION: Cancer cells were detected from pancreatic cancer exclusively,
      but K-ras point mutation at codon 12 was detected in pancreatic juice, not only
      from pancreatic cancer, but also from other diseases.

PMID- 8759673
TI  - Endoscopic cystgastrostomy: role of endoscopic ultrasonography.
AB  - We report a case of successful endoscopic cystgastrostomy guided by endoscopic
      ultrasound after an unsuccessful attempt of "blind" drainage. Endoscopic drainage
      of pseudocysts without endoscopic ultrasonography is an appropriate initial
      approach by experienced endoscopists in carefully selected patients. In cases in
      which an intraluminal impression by the pseudocyst is not well visualized, or the
      conventional approach has not established drainage, endoscopic ultrasound
      provides excellent localization for the therapeutic maneuver.

PMID- 8759674
TI  - Vanishing bile duct syndrome temporally associated with ibuprofen use.
AB  - Nonsteroidal anti-inflammatory drugs are widely used, but the potential
      hepatotoxic side effects are not always appreciated. Herein, we report the first
      case, to our knowledge, of an atopic patient in whom severe cholestatic jaundice
      from bile ductopenia developed 3 wk after initiation of ibuprofen therapy. This
      drug-induced vanishing bile duct syndrome is probably an immunological
      (hypersensitivity) reaction. Vanishing bile duct syndrome as a consequence of
      ibuprofen use should be considered as a potential cause of chronic cholestasis
      when other more common etiologies have been excluded.

PMID- 8759675
TI  - Pseudoxanthoma elasticum: a rare cause of gastrointestinal bleeding.
AB  - Pseudoxanthoma elasticum (PXE) is a rare connective tissue disorder. The main
      clinical features of this condition are characteristic skin lesions, angioid
      streaks of the fundus oculi, and occlusive vascular disease. Gastric hemorrhage
      is a rare complication. A gastroscopic examination was performed on two patients
      with PXE who presented with upper gastrointestinal tract bleeding. The two
      patients had submucosal yellowish nodular lesions similar to the xanthoma-like
      skin lesions seen in the disease. We suggest that a diagnosis of PXE be
      considered for any patient with gastrointestinal hemorrhage, especially if
      routine clinical and endoscopic examination fail to reveal the cause, and if
      raised yellow plaque-like lesions are seen in the stomach by endoscopy.

PMID- 8759676
TI  - Fibromuscular dysplasia of the visceral arteries.
AB  - Fibromuscular dysplasia (FMD) commonly involves the renal and carotid arteries.
      However, visceral arterial involvement is rare. We report a 39-yr-old male who
      developed ischemic bowel disease twice (once in the jejunal artery and once in
      the sigmoid artery) as a result of FMD. First ischemic change occurred in the
      sigmoid colon with manifestation of melena and abdominal pain, and the second
      occurred in the jejunum, with severe abdominal pain and intestinal stenosis.
      Angiography revealed the "string of beads" appearance, characteristic of FMD, in
      those two arteries responsible for the ischemic lesions. Fasting therapy with
      intravenous hyperalimentation improved both lesions, but secondary stenosis
      caused by ischemia occurred in the jejunum. Surgical resection of the stenotic
      jejunum was required. Although the abnormal arteries that had been imaged as a
      "string of beads" on angiography were not resected, the postoperative course has
      been uneventful and satisfactory.

PMID- 8759677
TI  - Endoscopic identification and removal of an unusual symptomatic esophageal
      foreign body.

PMID- 8759679
TI  - Liver abscess secondary to intrahepatic perforation of the gallbladder,
      presenting as a liver mass.
AB  - We present an unusual case of a large pyogenic liver abscess containing multiple
      stones caused by perforation of a necrotic gallbladder and spread of the
      infection into the liver. It manifested by weakness, weight loss, and a palpable
      liver mass, pointing toward a neoplastic process. Workup for metastatic disease
      was negative, and tumor markers also were negative. Ultrasound and computerized
      tomography were inconclusive, and the diagnosis was established by laparoscopy.
      Open drainage and cholecystectomy were performed, with good outcome. In the
      literature, there have been very few reports of intrahepatic perforation of the
      gallbladder resulting in formation of hepatic abscess. The presentation,
      diagnosis, and management of liver abscesses, as well as the complications of
      acute cholecystitis, are discussed.

PMID- 8759678
TI  - Minocycline-induced liver injury.
AB  - Tetracycline may cause fatty infiltration of the liver; more recently, it has
      been reported to cause intrahepatic cholestasis with bile duct depletion.
      However, minocycline, a derivative of tetracycline, is not generally recognized
      to be hepatotoxic. We report a series of six cases of presumed minocycline
      induced liver injury; five of these patients had acute hepatitic illness, whereas
      one had a more prolonged course with histological evidence of chronic hepatitis.
      In addition, three patients demonstrated abnormal anti-nuclear antibody levels,
      and one had positive double-stranded DNA.

PMID- 8759680
TI  - Diagnosis of gallbladder carcinoma with color Doppler ultrasonography.
AB  - A 65-yr-old woman was referred to our department for evaluation of a gallbladder
      lesion detected at another institution, where she was diagnosed with chronic
      cholecystitis. Conventional ultrasonography revealed that the gallbladder lumen
      was filled with debris-like components, and the gallbladder wall was mildly
      thickened. Color Doppler ultrasonography revealed color signals in both the
      lesion and the gallbladder wall. These signals showed a high-speed pulsatile
      wave, and one of the visualized signals revealed a high-resistance index (1.0) on
      fast Fourier transform analysis. These findings were highly suggestive of
      malignancy. Surgery was performed, and histological examination of the resected
      specimen revealed carcinoma of the gallbladder. We conclude that color Doppler
      ultrasonography can be useful in the diagnosis of tumefactive gallbladder
      lesions.

PMID- 8759681
TI  - Adenocarcinoma in situ in Barrett's esophagus with stricture of 10-yr duration: a
      cytological diagnosis.

PMID- 8759682
TI  - Orofacial lesions in Crohn's disease.
AB  - We describe a female patient with Crohn's disease who presented with longstanding
      gingival swelling. She went into remission after surgery, but had labial
      involvement while in remission. A review of the literature is presented with
      special reference to the clinical characteristics of orofacial Crohn's disease
      and Melkersson-Rosenthal syndrome, which can mimic such presentation of Crohn's
      disease.

PMID- 8759683
TI  - Short-segment jejunal stenosis complicating subacute portomesenteric venous
      thrombosis in a patient with protein S deficiency type II.

PMID- 8759684
TI  - Pemphigus vulgaris with asymptomatic pseudomembranous colitis.

PMID- 8759685
TI  - Spontaneous cholecystocutaneous fistula secondary to calculous cholecystitis.

PMID- 8759686
TI  - Localized epidermolysis bullosa acquisita of the esophagus in a patient with
      Crohn's disease.
AB  - Epidermolysis bullosa acquisita is a rare autoimmune subepidermal bullous disease
      that affects both the skin and mucosae and is frequently associated with Crohn's
      disease. We report the case of a 27-yr-old man with Crohn's disease who presented
      with localized epidermolysis bullosa acquisita of the esophagus, without any
      other mucosal or cutaneous lesions. The patient was successfully treated with
      sulfasalazine.

PMID- 8759687
TI  - A case of strangulated transomental hernia diagnosed preoperatively.
AB  - A patient with an unusual case of internal hernia was treated successfully with
      surgery for strangulated transomental hernia, diagnosed preoperatively by
      abdominal computed tomographic examination (CT). The herniation occurred through
      congenital defects in the gastrocolic omentum. Herniation of this nature is
      extremely rare, and abdominal CT examination is very useful for preoperative
      diagnosis.

PMID- 8759688
TI  - Pelvic-peritoneal tuberculosis simulating ovarian carcinoma: report of three
      cases with elevation of the CA 125.
AB  - We report three cases of women with abdominal pathology in which an elevated
      serum CA 125 tumor marker could have led to an erroneous diagnosis of ovarian
      carcinoma. However, after peritoneal biopsies were taken, tuberculosis was
      diagnosed. Furthermore, specific tuberculostatic treatment normalized serum CA
      125 levels.

PMID- 8759689
TI  - Clostridium difficile colitis: optimizing a cost-effective approach.

PMID- 8759690
TI  - Duodenogastroesophageal reflux parallels acid and not alkaline exposure in the
      esophagus and contributes to complications of reflux disease.

PMID- 8759691
TI  - First do no harm.

PMID- 8759692
TI  - Re: Constipation in an elderly community.

PMID- 8759694
TI  - Choice of HCV RNA level determination.

PMID- 8759695
TI  - Helicobacter pylori and lanzoprazole.

PMID- 8759696
TI  - Short-term low-dose triple therapy with lansoprazole plus amoxycillin and
      clarithromycin for Helicobacter pylori eradication.

PMID- 8759697
TI  - Additional potential candidates for hepatitis A vaccination.

PMID- 8759698
TI  - Re: Fecal occult blood testing.

PMID- 8759699
TI  - Comparison of ColoCARE versus Hemoccult SENSA for fecal occult blood testing in
      high-risk patients.

PMID- 8759700
TI  - Re: Clinical use of ColoCARE as a screening test for colorectal neoplasia.

PMID- 8759701
TI  - Interferon therapy for fulminant hepatitis associated with precore region
      mutation in hepatitis B virus carrier.

PMID- 8759702
TI  - Endosonography-guided celiac plexus injection for abdominal pain due to chronic
      pancreatitis.

PMID- 8759703
TI  - Mast cell infiltration and degranulation in colonic mucosa in the irritable bowel
      syndrome.

PMID- 8759704
TI  - Autonomic neuropathy in adult celiac disease.

PMID- 8759705
TI  - More intestinal worms on colonoscopy.

PMID- 8759706
TI  - Idiopathic thrombocytopenic purpura and pancytopenia in a patient with Crohn's
      disease: a new association.

PMID- 8759707
TI  - Etiology of gastric outlet obstruction.

PMID- 8759708
TI  - Pigmentation: a clue to hyperplastic right and transverse colon polyps.

PMID- 8759709
TI  - Systemic levels of soluble CD44 variant 6 (sCD44v6) in chronic inflammatory bowel
      disease.

PMID- 8759710
TI  - Beta-chemokine inhibition of monocytotropic HIV-1 infection. Interference with a
      postbinding fusion step.
AB  - The beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta have potent suppressive
      effects on HIV-1 infection resulting from an early postbinding block in virus
      fusion and entry. Inhibition was observed only with monocytotropic isolates and
      mapped to the V3 region of the HIV-1 envelope. RANTES did not inhibit virus
      expression in chronically infected cells or reduce initial virus attachment to
      the cell membrane. Inhibitory activity required RANTES binding to the target cell
      but not G protein-mediated signaling or protein tyrosine kinase activity. The
      results are consistent with a reversible competitive mechanism of virus
      inhibition that prevents a V3-associated postbinding step in membrane fusion. The
      data support a role for a RANTES chemokine receptor as a coreceptor for
      monocytotropic-HIV-1.

PMID- 8759711
TI  - CTLA-4 blockade enhances clinical disease and cytokine production during
      experimental allergic encephalomyelitis.
AB  - The B7 family of cell surface molecules expressed on APC provides accessory
      signals to T cells via either CD28 or CTLA-4. However, while CD28 transduces a
      costimulatory signal that is required for an optimal immune response, CTLA-4
      transmits a negative signal. These studies use an anti-CTLA-4 mAb to directly
      address the role of this T cell surface molecule in experimental allergic
      encephalomyelitis (EAE). CTLA-4 regulation of disease was assessed during initial
      immune cell interactions and during the effector stage of the encephalitogenic
      immune response. The effects of anti-CTLA-4 treatment were schedule dependent.
      CTLA-4 blockade during the onset of clinical symptoms markedly exacerbated
      disease, enhancing mortality. Disease exacerbation was associated with enhanced
      production of the encephalitogenic cytokines TNF-alpha, IFN-gamma and IL-2.
      Hence, CTLA-4 regulates the intensity of the autoimmune response in EAE,
      attenuating inflammatory cytokine production and clinical disease manifestations.

PMID- 8759712
TI  - Direct measurement of anergy of antigen-specific T cells following oral tolerance
      induction.
AB  - T cell tolerance induced by oral administration of Ag may be the result of either
      deletion or functional inactivation of Ag-specific T cells. OVA p(323-339)
      specific TCR transgenic (Tg+) lymphocytes were transplanted into BALB/c
      recipients. Chimeric mice were fed OVA and subsequently challenged with the
      peptide in CFA. Tolerance was then assessed by measurement of lymph node (LN)
      cell proliferation in response to the peptide, and deletion was assessed by
      measuring the frequency Tg+ T cells by flow cytometry. Lymphocytes from chimeric
      mice fed OVA showed a dose-dependent decline in their proliferative response to
      the peptide in vitro, compared with immunized control mice that were not fed OVA.
      Calculation of proliferative potential per Tg+ cell demonstrates that
      nonresponsiveness due to feeding Ag results in the induction of anergy in the LN.
      In addition, analysis of intestinal intraepithelial lymphocytes following feeding
      of OVA did not show evidence of trafficking of LN T cells to the small intestine
      intraepithelial nor lamina propria compartments.

PMID- 8759713
TI  - Naive murine neonatal T cells undergo apoptosis in response to primary
      stimulation.
AB  - The cellular mechanisms controlling deficient immune responses in newborn animals
      are not well understood. Our earlier studies showed that developmental regulation
      of Th cell activity may be one of the major causes of immunodeficiency in
      neonatal animals. Naive murine neonatal T cells showed poor Th1 activity but
      robust Th2 activity in response to primary stimulation in vitro. Although they
      produced high levels of IL-4, neonatal T cells proliferated poorly, suggesting
      that neonatal T cell survival in primary cultures may be limited. We show here
      that, unlike adult T cells, naive neonatal T cells undergo apoptosis in response
      to primary TCR-mediated stimulation. Ligation of the TCR alone, in the absence of
      accessory cell costimulation, is sufficient to induce apoptosis. Moreover, CD4+
      and CD8+ T cells show equivalent levels of apoptosis. Lastly, this apoptosis can
      be prevented by the addition of excess IL-2 or by conditions promoting a high
      level of IL-2 production (TCR-independent stimulation, anti-CD28 mAb, or
      exogenous IL-6) by neonatal T cells. However, IL-2 alone is not sufficient to
      support functional rescue from apoptosis; only IL-6 supports the ability of these
      cells both to survive and to mount vigorous secondary responses. The
      identification of conditions allowing functional rescue from apoptosis in vitro
      has important implications for enhancing vaccine responsiveness in vivo.

PMID- 8759714
TI  - A direct role for IFN-gamma in regulation of Th1 cell development.
AB  - IL-12 has been identified as a major cytokine influencing the differentiation of
      CD4 cells to a Th1 phenotype, whereas a role for IFN-gamma is controversial. We
      investigated the interrelationship between IL-12 and IFN-gamma in promoting Th1
      responses using naive CD4 cells reactive with pigeon cytochrome c from TCR
      transgenics and memory CD4 cells derived by in vivo priming with KLH. Without
      exogenous rIL-12 or rIFN-gamma, primary and memory effectors induced by Ag or
      anti-CD3 and anti-CD28 secreted variable levels of IL-2 and IFN-gamma. The level
      of IFN-gamma secreted by effectors correlated with endogenous IFN-gamma produced
      in primary cultures, and anti-IFN-gamma largely inhibited the development of
      effectors producing IFN-gamma. With optimal TCR stimulation and costimulation,
      endogenous IFN-gamma, without IL-12, was sufficient to elicit Th1 cells via an
      autocrine mechanism, whereas with suboptimal stimulation, exogenous rIFN-gamma or
      rIL-12 was required for Th1 development. However, rIL-12 was more effective than
      rIFN-gamma, partially because rIL-12 greatly enhanced autocrine production of IFN
      gamma, and optimal development of the Th1 phenotype was mediated by the
      synergistic actions of both cytokines. Thus, both IFN-gamma and IL-12 can
      independently regulate Th1 development, but because of IFN-gamma-mediated
      feedback, their relative contributions are determined by the conditions of T cell
      stimulation. The extent of differentiation to a Th1 phenotype may, therefore,
      depend on the availability of both APC-derived IL-12 and autocrine IFN-gamma
      consequent to the overall strength of T cell stimulation.

PMID- 8759715
TI  - Bcl-2 expression inhibits prostaglandin E2-mediated apoptosis in B cell
      lymphomas.
AB  - Apoptosis is a critical mechanism in the maturation and maintenance of the immune
      system. However, the process by which cells die remains poorly understood. The
      proto-oncogene bcl-2 is considered important in determining whether cells enter
      an apoptotic pathway or survive. In this report, we first examined the
      differential sensitivity of immature (CH31) and mature (CH12) B cell lymphomas to
      growth inhibition by PGE2. The CH31 cell line was growth inhibited and underwent
      apoptosis in response to PGE2, unlike its mature counterpart, CH12. Furthermore,
      endogenous levels of the anti-apoptotic protein Bcl-2 in CH31 cells were low
      compared with CH12. To further investigate the role of Bcl-2 in PGE2- and cAMP
      mediated cell death, a retroviral vector bearing the human bcl-2 gene was
      introduced into CH31. High expression of Bcl-2 in CH31 had no effect on growth
      inhibition induced by PGE2 or dibutyryl cAMP. In contrast, increased expression
      of Bcl-2 completely inhibited PGE2- and cAMP-mediated DNA fragmentation and
      nuclear condensation. Finally, cell cycle analysis of Bcl-2-expressing CH31 cells
      demonstrated that PGE2 increased the percentage of cells in G1, and analysis of
      synchronized populations revealed that PGE2 acts at all phases of the cell cycle
      to delay normal progression. These results support the hypothesis that apoptosis
      induced through PGE2 and cAMP signaling is sensitive to regulation by Bcl-2 in
      CH31 B cell lymphomas. Furthermore, unlike apoptosis, regulation of PGE2- and
      cAMP-mediated growth inhibition in B lineage cells is a distinct and Bcl-2
      independent mechanism.

PMID- 8759716
TI  - Murine T lymphocytes modulate activity of an ATP-activated P2Z-type purinoceptor
      during differentiation.
AB  - Murine T, but not B, lymphocytes constitutively express a membrane receptor for
      adenosine nucleotides that opens a nonspecific pore that admits Ca2+ and ethidium
      (314 Da), but not propidium (415 Da) ions. ATP, ADP, and AMP show decreasing
      potency; UTP and adenosine are inactive. Nonhydrolyzable ATP analogues are
      completely ineffective. Oxidized ATP inhibits the response. Activity is
      detectable at ATP concentrations of 125 microM and peaks at 1 mM. The
      intracellular free Ca2+ ([Ca2+]i) rise is not reversed by removing ATP by
      centrifugation or apyrase. The kinetics, agonist and antagonist profiles, and the
      passage of ions as large as ethidium are the characteristics of a P2z-type
      purinoceptor. No expression of classical P2x-, P2u-, or P2Y-type purinoceptors
      can be detected. The [Ca2+]i elevating activity of the ATP receptor is modulated
      during T cell differentiation. CD4+8+ double-positive thymocytes are the least
      responsive. CD4-8+ single-positive thymocytes, CD8+ splenic T cells, CD4+8-
      single-positive thymocytes, and CD4+ splenic T cells show increasing reactivity.
      Measurement of P2Z expression by the rate of ethidium ion uptake correlates with
      the [Ca2+]i. The trimodal expression of P2Z by splenic CD4+ T cells correlates
      with the subsets defined by CD44 and CD45RB, differentiation Ags that distinguish
      memory cells: P2Zlow cells are CD44brightCD45RBbright; P2Zint are
      CD44dullCD45RBint; P2Zhigh are CD44brightCD45RBdull. It is suggested that P2Z
      receptor-mediated signaling could be involved in the regulation of
      differentiation and cell death in the thymus and peripheral T lymphocytes.

PMID- 8759717
TI  - Coordinated regulation in human T cells of nucleotide-hydrolyzing ecto-enzymatic
      activities, including CD38 and PC-1. Possible role in the recycling of
      nicotinamide adenine dinucleotide metabolites.
AB  - The human leukocyte surface Ag CD38 was recently identified as a nicotinamide
      adenine dinucleotide (NAD)(+)-glycohydrolase ecto-enzyme, degrading NAD into
      nicotinamide and ADP-ribose. We show here that expression of CD38 is increased in
      the Jurkat T cell line after treatment with agents that augment intracellular
      cAMP, with the permeant cAMP analogue dibutyryl-cAMP (db-cAMP), and also with
      PMA, which activates protein kinase C. Treatment of human PBL T cells with db
      cAMP or submitogenic doses of PMA also increased CD38 expression. Two other
      nucleotide-hydrolyzing activities were induced on the T cell surface
      concomitantly with CD38: the human PC-1 molecule, a nucleotide
      phosphodiesterase/pyrophosphatase that produces AMP from NAD or ADP-ribose, and a
      nucleotidase that produces adenosine from AMP, but which may be distinct from the
      CD73 5'-nucleotidase. All three enzymes were up-regulated after stimulation of
      human peripheral blood T cells with PHA. The coordinated regulation of these ecto
      enzymes suggested that, besides a possible signaling function, they may recycle
      extracellular NAD by degrading it to adenosine and nicotinamide, which can be
      taken up by cells. In support of this hypothesis, db-cAMP-treated Jurkat cells
      could degrade extracellular NAD for de novo synthesis of purines, while untreated
      cells could not. Activated lymphocytes are often located in tissues in which cell
      death is common. It is suggested that the coordinated expression of these enzymes
      may allow activated T cells to re-use NAD and nucleotides from dead cells.

PMID- 8759718
TI  - Activated B cells express CD28/B7-independent costimulatory activity.
AB  - Resting and activated B cells display distinct phenotypes and functional
      properties. Resting B cells are incompetent accessory cells whereas activated B
      cells are capable of triggering T cell activation. The up-regulation of
      expression of the B7 family of molecules has been considered to be the primary
      reason for this functional conversion of activated B cells. We report here that
      activation of B cells induces a novel costimulatory activity for induction of T
      cell proliferation, which is independent of the CD28/B7 costimulatory pathway. B
      cells activated by different stimuli expressed comparable levels of many of the
      known counter-receptors for costimulation and intercellular adhesion (B7-1, B7-2,
      HSA, ICAM-1), but differed markedly in their capacity to activate CD4+ T cells
      from CD28-deficient (-/-) mice. Activation of B cells via CD40, and to a lesser
      extent with LPS, induced potent B7/CD28-independent costimulatory activity that
      resulted in marked augmentation of IL-2-mediated proliferative responses of CD4+
      T cells from CD28 -/- mice. The B7/CD28-independent costimulatory pathway was
      capable of triggering the activation of naive CD4+ T cells, as both sorted
      CD45RBhigh and isolated high density naive CD4+ T cells from CD28 -/- mice
      responded vigorously to the costimulation provided by CD40L-activated B cells.

PMID- 8759719
TI  - Reciprocal regulation of mucosal surface IgA+ B cells by Ig receptor cross
      linking and CD40 ligand.
AB  - In the present study, we analyze the role of Ig receptor cross-linking in T cell
      dependent stimulation of both preswitch (surface IgM+ (sIgM+/sIgD+) B cells and
      postswitch (sIgA+) B cells. We demonstrate that purified sIgA+ B cells pretreated
      with anti-IgA-dextran at low concentrations (10 and 100 ng/ml) exhibited an
      increased response to activated T cells, whereas pretreatment with higher doses
      (1 and 10 micrograms/ml) led to a profound suppression of IgA secretion (> or =
      90%). The suppressive effect of anti-IgA-dextran was accentuated in the presence
      of IL-2 and attenuated in the presence of IL-4. Anti-IgA-dextran pretreatment had
      no effect on sIgA+ B cell survival. sIgM+/sIgD+ B cells pretreated with anti-IgD
      dextran or anti-IgM-dextran did not show significant inhibition. The increased
      susceptibility of sIgA+ B cells, but not of sIgM+/sIgD+ B cells, to Ig cross
      linking-mediated suppression was confirmed in cross-linking studies with the same
      Ab (anti-kappa-dextran). Importantly, anti-IgA-dextran-mediated suppression could
      be reversed by stimulation of sIgA+ B cells with fibroblasts expressing CD40L;
      such a reversal required persistent exposure to cells expressing high levels of
      CD40L. These studies imply that Ig receptor cross-linking renders postswitch
      sIgA+ B cells unresponsive to subsequent stimulation via activated T cells, but
      this unresponsiveness is overcome by a persistent high level CD40L signal.

PMID- 8759720
TI  - Dendritic cells can present antigen in vivo in a tolerogenic or immunogenic
      fashion.
AB  - Dendritic cells (DC) are unmatched among APCs in their ability to bind, process,
      and present Ag. Presentation by such potent APCs, if always immunogenic and never
      tolerogenic, might stimulate pathogenic autoimmune responses. To determine
      whether Ag presentation by DC can induce tolerance, mice were injected with a rat
      IgG2b anti-splenic DC mAb, 33D1, and challenged 13 to 28 days later with a
      stimulatory rat IgG2b mAb. Injection of mice with 1 ng/100 micrograms of 33D1
      rarely induced an anti-rat IgG2b Ab response and, in most mice, induced rat IgG2b
      specific T cell and B cell tolerance. Tolerant mice had decreased ability to
      secrete Ab and make both type 1 and type 2 cytokine mRNA and protein in response
      to immunization with rat IgG2b. 33D1 was 100- to 1000-fold more potent as a
      tolerogen than an isotype-matched control rat IgG2b mAb. Injecting mice with
      aggregated 33D1, 33D1 plus anti-IgD mAb, or 33D1 plus IL-1 induced an IgG1 anti
      rat IgG2b Ab response rather than tolerance. IL-1 injected 3 days after 33D1
      still induced an Ab response rather than tolerance. Not all anti-DC mAbs are
      tolerogenic. Injection of a DC-specific hamster anti-CD11c mAb (N418) stimulates
      an IgG anti-hamster response, and injection of 33D1 plus N418 stimulates both
      anti-hamster and anti-rat IgG2b responses. These observations indicate that DCs
      can present Ag in either a tolerogenic or stimulatory manner and suggest that
      inflammatory stimuli can convert an otherwise tolerogenic signal to a stimulatory
      signal.

PMID- 8759721
TI  - Inhibition of transcription factor Stat1 activity in mononuclear cell cultures
      and T cells by the cyclic AMP signaling pathway.
AB  - Activation of T cells results in a cascade of gene activation and subsequent
      proliferation and differentiation into effector phenotypes. The regulation of
      transcription factors belonging to the signal transducer and activator of
      transcription (STAT) family was analyzed in PHA-activated mononuclear cells and
      in purified T cells activated by cross-linking cell surface CD3. Cell activation
      resulted in a delayed induction of STAT DNA-binding activity, which was sustained
      for several days, was composed predominantly of Stat1 and Stat3, and was blocked
      by cycloheximide and actinomycin D. Increased Stat1 and Stat3 mRNA and protein
      levels were detected, respectively 4 and 24 h after activation. Stimulation of
      the cAMP signal transduction pathway, which skews cytokine production toward a
      Th2 pattern, resulted in the preferential suppression of Stat1 activity. cAMP
      inhibited the induction of expression of IL-2 receptor components, but did not
      inhibit IL-4 receptor alpha-chain and CD69 expression or the induction of
      activator protein 1 transcription factors. cAMP signaling inhibited Stat1 at
      several different levels, including suppression of DNA binding and down
      regulation of Stat1 protein and mRNA levels. Our results demonstrate the
      regulation of STAT activity by a signaling pathway that regulates the T cell
      functional phenotype and is distinct from the cytokine-activated Janus kinase
      STAT signaling pathway.

PMID- 8759722
TI  - Implantation of IL-2-containing osmotic pump prolongs the survival of
      superantigen-reactive T cells expanded in mice injected with bacterial
      superantigen.
AB  - In the present study we investigated the mechanism of deletion of superantigen
      (sAg)-reactive T cells expanded in sAg-injected mice. In staphylococcal
      enterotoxin A (SEA)-injected mice, IL-2 activity in serum peaked at 1 to 3 h and
      the expression of IL-2R alpha-chain (IL-2R alpha) on SEA-reactive (V beta 3+, or
      V beta 11+) T cells peaked at 6 to 12 h after the injection. Expansion of V beta
      3+ or V beta 11+ T cells peaked at 2 days after the injection when most of these
      T cells were IL-2R alpha negative, and IL-2 activity was not detected at all in
      serum, suggesting the involvement of IL-2 deprivation in the deletion of expanded
      T cells. Implantation of an osmotic pump containing human rIL-2 (IL-2 pump)
      prolonged the expanded states of V beta 3+ or V beta 11+ T cells in SEA-injected
      C57BL/6 mice and of V beta 8+ T cells in SEB-injected MRL +/+ and Fas Ag
      defective MRL-Ipr/Ipr mice. Adult thymectomy did not change at all the effect
      induced by implantation of IL-2 pump. DNA fragmentation was blocked substantially
      in mice co-treated with SEA and IL-2 pump. In addition, CD4+ T cell blasts,
      obtained by in vitro stimulation with rIL-2 of splenic CD4+ T cells from mice co
      treated with SEA and IL-2 pump, produced substantial amounts of IL-2 upon
      restimulation with SEA. These results indicate that deprivation of IL-2 is deeply
      involved in the deletion of expanded sAg-reactive T cells and their anergy
      induction in sAg-injected mice.

PMID- 8759723
TI  - Nebulized IFN-gamma inhibits the development of secondary allergic responses in
      mice.
AB  - The effects of nebulized IFN-gamma on primary and secondary IgE production and
      development of airway hyper-responsiveness (AHR) were investigated. BALB/c mice
      received primary exposure to aerosolized OVA daily for 10 days and developed anti
      OVA IgE responses, immediate cutaneous reactivity to OVA, and altered airway
      function when assayed on day 12. After secondary exposure to OVA challenges on
      days 30 and 31, these mice developed an amplified IgE response, heightened
      cutaneous reactivity to OVA and AHR when measured on day 37. Administration of
      IFN-gamma for 13 days, beginning 3 days prior to and during primary OVA
      sensitization, resulted in a decrease in anti-OVA IgE, increases in serum anti
      OVA IgG2a levels, a decrease in cutaneous reactivity to OVA, and normal airway
      function when assessed on day 12 after primary sensitization. This treatment also
      prevented the development of secondary anti-OVA IgE responses and altered airway
      responsiveness but did not induce a secondary rise in anti-OVA IgG2a in the serum
      measured on day 37. Treatment with IFN-gamma on days 26 to 30, well after primary
      responses were established but just prior to secondary OVA challenge, abolished
      the development of secondary anti-OVA IgE responses, resulted in an increase in
      anti-OVA IgG2a in the serum, and prevented the development of AHR. In vitro, CD4+
      T cells obtained from OVA-sensitized mice treated with either "early" or "late"
      IFN-gamma inhibited IgE production. Delivery of IFN-gamma to the airways can
      prevent secondary allergen sensitization even after primary sensitization has
      been achieved and this effect is mediated by CD4+ T cells.

PMID- 8759724
TI  - CD40 ligation results in protein kinase C-independent activation of ERK and JNK
      in resting murine splenic B cells.
AB  - CD40 is a 45- to 50-kDa transmembrane glycoprotein that plays an important role
      in B cell proliferation, survival, memory, and Ig isotype switching. How CD40
      engagement couples to these distal events in B cell activation remains poorly
      understood. In this study, we have examined signal transduction events mediated
      by CD40 cross-linking in resting murine splenic B cells. In comparison to
      signaling via the B cell Ag receptor (BCR), CD40 cross-linking was less effective
      at activating protein tyrosine kinases. Interestingly, however, CD40 engagement
      resulted in the phosphorylation of both extracellular signal-regulated protein
      kinase (ERK) and the Ras guanine nucleotide exchange factor, Son of sevenless. In
      addition, both ERK and c-Jun NH2-terminal kinase activities were increased after
      both CD40 and BCR ligation. Overnight treatment of cells with phorbol ester as
      well as pharmacologic inhibitors of protein kinase C abrogated these signaling
      events after BCR treatment; however, no effect was seen on CD40-mediated
      activation of ERK or c-Jun NH2-terminal kinase, suggesting that the BCR and CD40
      differentially utilize protein kinase C to couple with these signaling pathways.

PMID- 8759725
TI  - Expression of the CTL-associated protein TIA-1 during murine embryogenesis.
AB  - TIA-1 is a T cell-associated protein that binds poly(A) in vitro and induces
      apoptosis in permeabilized thymocytes. It may be involved in the induction of
      apoptosis in target cells during lymphocyte attack. To elucidate the role of TIA
      1 in mammalian development, a cDNA-encoding mouse TIA-1 was cloned. The predicted
      mouse TIA-1 protein contains three RNA binding domains at the amino terminus and
      a putative lysosomal targeting sequence at the carboxyl terminus. The mouse
      sequence shows 96% overall identity with the human TIA-1 homologue. During murine
      embryogenesis, abundant mouse TIA-1 mRNA is detectable from 12.5 days of
      development onward in the brain and the retina, where it is selectively expressed
      within neuronal cells. Transcripts are also found in the lung, kidney, and
      thymus. TIA-1 in the adult mouse is expressed mainly in T cells and NK cells. The
      expression of TIA-1 during mouse embryogenesis is endogenous to tissues in which
      apoptotic cell death occurs. The conservation of this RNA-binding protein
      throughout evolution implicates its importance in embryogenesis, and in
      particular neuronal development.

PMID- 8759726
TI  - Signaling through CD38 augments B cell antigen receptor (BCR) responses and is
      dependent on BCR expression.
AB  - mAbs directed against the ectoenzyme CD38 will induce B cell proliferation in
      normal resting B lymphocytes, but cannot induce proliferation in B cells that are
      unresponsive to B cell Ag receptor (BCR) cross-linking. Using the CD38- murine B
      cell line A20 we have examined the relationship between CD38- and BCR-mediated
      signaling after transfection of wild-type or mutant CD38 molecules. Although
      association between CD38 and the BCR was not detectable, co-cross-linking of CD38
      and the BCR gave rise to a synergistic response, and expression of CD38 lowered
      the threshold for BCR-induced responses. Generation of Ig loss variant clones
      established that coexpression of the BCR was required for CD38-mediated signal
      transduction. The cytoplasmic tail of Ig alpha or Ig beta rescued CD 38
      responsiveness in the CD38+Ig- cells provided that the chimeric molecules were
      coligated with CD38. Separate experiments indicated that the cytoplasmic tail of
      CD38 is not required for CD38 signaling. The anti-CD38-induced response was
      dependent on the influx of extracellular calcium but was not accompanied by
      detectable tyrosine phosphorylation of any cellular proteins. Together, these
      data demonstrate that the CD38 molecule can influence BCR-induced responses and
      that CD38 signaling is dependent on the BCR complex, perhaps to utilize a
      functional cytoplasmic tail(s) for intracellular signaling.

PMID- 8759727
TI  - Tyrphostin A9 inhibits calcium release-dependent phosphorylations and calcium
      entry via calcium release-activated channel in Jurkat T cells.
AB  - The mechanism by which calcium-depleted intracellular stores may trigger an
      external calcium influx through a calcium release-activated channel was
      investigated by analyzing the effects of several protein tyrosine kinase
      inhibitors on calcium movements in Jurkat T cells. Tyrphostin A9, an inhibitor of
      the kinase activity of the platelet-derived growth factor (PDGF) receptor,
      dramatically impaired the sustained elevation of cytosolic calcium concentration,
      induced by either CD3 mAbs, thapsigargin, ionomycin at low (10(-7) M)
      concentration, or passive depletion of intracellular stores; other tested
      tyrphostins, lavendustin, genistein, and compound 5 lacked significant effect.
      Tyrphostin A9, added during the plateau phase, was able to return cytosolic
      calcium to resting concentration. Likewise, it abrogated manganese entry in cells
      stimulated by CD3 or thapsigargin, measured by the quenching of the fluorescence
      of Indo-1. However, it did not measurably modify kinetics of intracellular
      calcium releases monitored in the absence of extracellular calcium, nor did it
      reverse the inhibition of phosphatidylserine that occurs as a consequence of
      emptying intracellular stores. Analyses of tyrosine phosphorylations demonstrated
      that A9 inhibited the phosphorylation of proteins, which occurred every time that
      internal calcium stores were depleted. These phosphorylations were not impaired
      by chelation of external Ca2+, nor by La3+ that inhibits calcium release-induced
      calcium entry. We concluded that their inhibition was not a consequence, but may
      be a cause, of the blockade of calcium release-activated channel by tyrphostin
      A9.

PMID- 8759728
TI  - B cells selected for apoptosis in the sheep ileal Peyer's patch have enhanced
      mutational diversity in the Ig V lambda light chain.
AB  - To investigate the molecular events associated with B cell apoptosis, we analyzed
      follicular B cells from the large Peyer's patch (PP) in the sheep ileum. Over 95%
      of B cells generated in the ileal PP are rapidly destroyed by apoptosis. Ig V
      lambda sequences from apoptotic B cells were compared with sequence from B cells
      about to emigrate from the PP. The sequences originated from two germline genes,
      V lambda 5.1 and V lambda 5.3. Only V lambda 5.1 was rearranged in apoptotic
      cells, whereas both V lambda 5.1 and V lambda 5.3 were rearranged in B cells
      about to emigrate. Apoptotic B cells had evidence of increased Ig sequence
      diversity based on: 1) significantly greater replacement to silent mutation
      ratios in the complementarity determining regions, 2) the more random
      distribution of mutations, and 3) the lack of mutational specificity compared
      with the mutational bias favoring transitions and purines in B cells about to
      emigrate. Based on this analysis, we propose that the continual proliferation of
      B cells in the PP follicle might increase their affinity to local Ags. Those Ags
      that are sequestered in this environment might be expected to stimulate the
      production of B cells with such high-affinity receptors that ligation would
      trigger apoptosis. This could account for the deletion of B cells with
      specificity for self-antigens, selecting ligands as well as gut-derived food and
      microbial Ags. This process could contribute to the elimination of self-reactive
      B cells, the expansion of the antibody repertoire, and the generation of oral
      tolerance.

PMID- 8759729
TI  - Physical and functional association of Fc mu receptor on human natural killer
      cells with the zeta- and Fc epsilon RI gamma-chains and with src family protein
      tyrosine kinases.
AB  - We recently reported that Fc mu R on NK cells is a signal transducing protein
      that stimulates a rapid increase in the level of cytoplasmic free calcium upon
      binding of IgM. This study was designed to examine signal transduction via the Fc
      mu R on NK cells and to characterize intracellular second messengers activated by
      IgM. Immunoprecipitation of IgM-bound Fc mu R by IgM-specific Ab
      coimmunoprecipitated the zeta- and Fc epsilon RI gamma-chains. Furthermore,
      engagement and clustering of Fc mu R by polyclonal IgM induced tyrosine
      phosphorylation of the zeta- and Fc epsilon RI gamma-chains, indicating their
      functional association with the Fc mu R-induced signal transduction cascade.
      Ligand-induced clustering of the Fc mu R also induced activity of src family
      kinases, Lck, Fyn, Lyn, and Src, as well as their physical interaction with the
      receptor. Triggering via Fc mu R also induced the activity of Syk and Zap-70,
      tyrosine kinases demonstrated to associate with zeta and Lck. Phospholipase C
      gamma 1 and phosphatidylinositol 3-kinase were identified as substrates
      phosphorylated on tyrosine, as down-stream components of the signaling pathway
      activated in NK cells by polyclonal IgM. Although the Fc mu R on NK cells has not
      yet been biochemically characterized, our results suggest that the zeta- and Fc
      epsilon RI gamma-chains are functional subunits of this as well as other
      important cell surface receptors and that the Fc mu R is coupled either directly
      or indirectly to nonreceptor tyrosine kinases, which phosphorylate and thereby
      activate regulatory enzymes such as phospholipase C-gamma 1 and
      phosphatidylinositol 3-kinase.

PMID- 8759730
TI  - Somatic mutations in human Ig variable genes correlate with a partially
      functional CD40-ligand in the X-linked hyper-IgM syndrome.
AB  - X-linked hyper-IgM (HIGM-1) syndrome is a rare disorder resulting from mutations
      in the CD40-ligand (CD40L) gene. This defect is associated with normal or
      elevated serum levels of IgM, and with low to undetectable levels of serum IgG,
      IgA, and IgE. We analyzed the somatic mutation status in Ig V genes from three
      unrelated HIGM-1 patients by reverse-transcription PCR and sequence analysis. Two
      patients (B.S. and P.S.) expressed unmutated VH6 genes. In contrast, one patient
      (A.T.) was found to express mutated VH6 genes. Whether the presence of somatic
      mutations in this patient was related to a functional CD40L was assessed by
      deriving T cell clones from his peripheral blood cells. Upon activation, these T
      cell clones expressed weakly and transiently surface CD40L, and were able to
      induce limited isotype switch of normal native B cells, indicating residual CD40L
      function. Altogether, our results 1) confirm the central role played by CD40L in
      the generation of somatic mutation (patients B.S. and P.S.), 2) provide an
      unusual illustration of the relative dissociation between somatic mutation and
      isotype switching (patient A.T.), and 3) demonstrate a further complexity of the
      X-linked HIGM syndrome that may occur despite a partially functional CD40L.

PMID- 8759731
TI  - TGF-beta 1 promotes in vitro development of dendritic cells from CD34+
      hemopoietic progenitors.
AB  - Several studies have demonstrated that dendritic cells (DC) can be generated in
      vitro from CD34+ hemopoietic progenitor cells. The growth requirements for these
      cells are poorly characterized, however. In particular, undefined serum/plasma
      components seem to significantly contribute to in vitro DC development. We report
      here that the cytokine combination granulocyte-macrophage CSF (GM-CSF) plus TNF
      alpha and stem cell factor (SCF) commonly used for the in vitro generation of DC
      in serum/plasma-supplemented medium is, in the absence of serum supplementation,
      very inefficient in inducing DC development. We further demonstrate that
      supplementation with TGF-beta 1 is required for substantial DC development to
      occur in the absence of serum. Culture of CD34+ cells under serum-free conditions
      with TGF-beta 1 plus GM-CSF, TNF-alpha, and SCF strongly induces DC
      differentiation. This culture condition is even more efficient than culturing
      CD34+ cells with GM-CSF plus TNF-alpha and SCF in the presence of cord blood
      plasma. The proportions and total yields of cells with typical DC morphology and
      CD1a molecule expression are higher. The allostimulatory capacity of DC from TGF
      beta 1-supplemented, cultures exceeds allostimulation by cells grown in plasma
      containing medium. Substantial numbers (21 +/- 7%) of cells grown in TGF-beta 1
      supplemented, but not plasma-supplemented, cultures express the Birbeck granule
      marker molecule Lag and display numerous Birbeck granules. Cells with distinct
      monocytic features are less frequently observed in TGF-beta 1-supplemented serum
      free cultures. The addition of neutralizing anti-TGF-beta 1 Ab abrogates the
      observed TGF-beta 1 effects.

PMID- 8759732
TI  - Phorbol ester and calcium ionophore can replace TCR signals that induce positive
      selection of CD4 T cells.
AB  - Positive selection of immature thymocytes is a developmental process in which TCR
      ligation by low avidity interaction induces the generation of mature T cells.
      However, biochemical signals that can induce positive selection have been
      unclear. By using TCR-alpha beta- mutant thymus cultures, the present study shows
      that direct stimulation of intracellular signals by PMA and calcium ionophore
      ionomycin can induce the generation of mature CD4+8- T cells, bypassing TCR
      induced positive selection signals. Interestingly, the concentrations of phorbol
      ester that induced positive selection were more restricted than those that
      induced mature T cell activation. Moreover, the combination of phorbol ester and
      ionomycin restored the generation of CD4+8- T cells in class II MHC- thymus
      cultures, but did not induce the generation of CD4-8+ T cells in class I MHC-
      thymus cultures. These results identify that the combination of protein kinase C
      activation and calcium elevation is the biochemical signal that can induce
      positive selection of CD4+ T cells.

PMID- 8759733
TI  - Inhibition of T lymphocyte activation by cAMP is associated with down-regulation
      of two parallel mitogen-activated protein kinase pathways, the extracellular
      signal-related kinase and c-Jun N-terminal kinase.
AB  - The induction of T cell proliferation requires signals from the TCR and a co
      receptor molecule, such as CD28, that activate parallel and partially cross
      reactive signaling pathways. These pathways are disrupted by agonists that
      utilize adenylate cyclase and cAMP-dependent protein kinase A (PKA). We found
      that the adenylate cyclase activator, forskolin, inhibits anti-CD3-induced shift
      in Lck electrophoretic mobility, suggesting an intervention at the TCR-coupled
      phosphoinositide turnover that precedes the activation of PKC. The shift of Lck
      following direct PKC activation by 12-O-tetradecanoyl phorbol 13-acetate, which
      bypasses early receptor-triggered biochemical events, is insensitive to
      forskolin. Nevertheless, forskolin also inhibits PKC downstream events, such as c
      jun expression, which is critical for the activation process of T cells. To
      further analyze potential cross points between positively and negatively
      regulating signaling pathways in T cells, we tested the effects of activators of
      the adenylate cyclase or PKA on two parallel mitogen-activated protein kinase
      signaling pathways mediated by extracellular signal-regulated kinase (ERK) and c
      Jun N-terminal kinase. Using a PKC-specific inhibitor, GF109203X, or PKC-depleted
      T cells, we found that a large part of the anti-CD3-induced ERK activation is PKC
      dependent. Both PKC-dependent and -independent activation of ERK were sensitive
      to inhibition by forskolin or a cell-permeable cAMP analogue, dbcAMP.
      Furthermore, the effect of 12-O-tetradecanoyl phorbol 13-acetate and ionomycin,
      which synergized to fully activate c-Jun N-terminal kinase, was also sensitive to
      inhibition by forskolin. Our results suggest that PKA inhibits T cell activation
      by interfering with multiple events along the two signaling pathways operating
      downstream of the TCR and the CD28 co-receptor molecules.

PMID- 8759734
TI  - Enhanced generation of NK cells with intact cytotoxic function in CD45 exon 6
      deficient mice.
AB  - CD45 is a cell membrane-type protein tyrosine phosphatase that is essential for
      Ag receptor-mediated signaling in both T and B lymphocytes. To characterize roles
      of CD45 molecules in murine NK cells, we analyzed the development and the
      cytotoxic functions of NK cells in mice lacking CD45 exon 6 (CD45 -/-). A
      markedly increased number of NK cells was observed in spleens of the CD45 -/-
      mice, despite no CD45 surface expression on the NK cells. From the results of
      mixed bone marrow chimera experiments, it was demonstrated that the expansion of
      NK cells in CD45 -/- mice was due to the influence of disappeared expression of
      CD45 in the NK cells per se, but not to the modulation of environmental factors.
      The NK cells in the CD45 -/- mice had normal cytotoxic activities, including NK
      and Ab-dependent cell-mediated cytotoxicity activities comparable with those in
      normal mice (CD45 +/+). Additionally, the CD45 -/- NK cells could functionally
      differentiate to lymphokine-activated killer cells by culturing with a high dose
      of IL-2, despite a lack of induced expression of B220. Therefore, these results
      suggest that CD45 is involved in NK cell development, but is not essential for
      cytotoxic activities and Fc gamma R-mediated signaling in NK cells.

PMID- 8759735
TI  - Cytokine-mediated communication between dendritic epidermal T cells and
      Langerhans cells. In vitro studies using cell lines.
AB  - Murine epidermis contains two leukocyte populations: Langerhans cells (LC), which
      are APC of dendritic cell (DC) lineage, and dendritic epidermal T cells (DETC),
      which are members of the tissue-type gamma delta T cell family. Despite close
      physical approximation in vivo, the extent to which LC and DETC affect each
      other's function has remained unknown. We addressed this question using the long
      term DC line XS52 and the gamma delta T cell line 7-17, both of which were
      established from mouse epidermis, and both of which retain important features of
      the resident populations from which they were derived. XS52 DC proliferated
      maximally when cocultured with gamma-irradiated 7-17 DETC. They also proliferated
      in response to culture supernatants collected from anti-CD3- or Con A-activated 7
      17 DETC, but not from nonstimulated DETC. In both systems, DETC-induced XS52 DC
      growth was inhibited partially (up to 70%) by Abs against granulocyte/macrophage
      CSF (GM-CSF) or CD115 (CSF-1 receptor) and nearly completely (up to 90%) by both
      together. Among 28 tested cytokines, only GM-CSF, CSF-1, IL-4, and IL-13 promoted
      XS52 DC growth significantly. Anti-IL-4 failed to inhibit DETC-induced XS52 cell
      growth, and IL-4 was not detectable in DETC supernatants. Thus, we conclude that
      GM-CSF and CSF-1 (and perhaps IL-13) account for the DC growth-promoting activity
      secreted by DETC. These results suggest that during coculture, XS52 DC activate 7
      17 DETC to secrete both GM-CSF and CSF-1. In fact, when cultured with XS52 DC, 7
      17 DETC also elevated their expression of the gamma c receptor and acquired
      proliferative responsiveness to their own growth factor IL-15. We propose that LC
      and DETC in situ may interact with each other in a similar manner, thereby
      regulating their residence and function.

PMID- 8759736
TI  - The transcription factor B-cell-specific activator protein is not involved in the
      IL-4-induced activation of the human IgE germline promoter.
AB  - Transcriptional activity of the human IgE germline gene is a prerequisite for a
      subsequent deletional rearrangement of the Ig heavy-chain locus, the hallmark of
      isotype switching to IgE. The B-cell-specific transcription factor B cell
      specific activator protein (BSAP) was described for being critically involved in
      the IL-4 up-regulation of the murine IgE germline gene. Our study was initiated
      to evaluate the regulatory role of BSAP in the human IgE germline promoter. It is
      shown that BSAP binds to a DNA element located immediately upstream of the most
      5' transcriptional start site. The authenticity of BSAP was determined by
      electrophoretic mobility shift assays in which oligonucleotides corresponding to
      published BSAP binding sites efficiently competed for binding to the novel
      identified sequence. In addition, recombinant purified BSAP protein bound this
      motif and comigrated with the band seen with nuclear extracts. Finally, a
      polyclonal anti-BSAP antiserum specifically prevented interaction of the protein
      with its DNA recognition sequence. The affinity of BSAP for its recognition
      sequence was low compared with the sites identified in the CD19, the blk gene,
      and an LR1 transcription factor binding sequence located in the Ig gamma 1 switch
      region. Reporter gene constructs in which binding of BSAP was abolished by site
      directed mutagenesis responded to IL-4 stimulation better than the wild-type
      construct in both cell lines tested. In addition, the basal activity of the
      mutated promoter did not change significantly despite the close proximity of the
      BSAP motif to the transcriptional start site. It is concluded that BSAP plays no
      direct regulatory role in the cytokine-induced response of the human IgE germline
      promoter.

PMID- 8759737
TI  - A third Ig light chain gene isotype in Xenopus laevis consists of six distinct VL
      families and is related to mammalian lambda genes.
AB  - Xenopus laevis is a unique model for studying the ontogenetic development of
      immune functions. A short primer PCR amplification method was employed to amplify
      fragments from Xenopus genomic DNA that are related to Ig light chains and TCR.
      One fragment was identified that appeared to represent a novel type of light
      chain and was used as a probe to recover the corresponding cDNA from a spleen
      cDNA library. We designate these light chains type III. Using an iterative
      screening procedure, six families of VL genes, two distinct JL and two distinct
      CL sequences, were identified. In a comparison of phylogenetically diverse light
      chains, the type III genes align with higher vertebrate lambda genes. Southern
      blot hybridization analyses with genomic DNA from different animals showed the VL
      and CL sequences to be both diverse and polymorphic. Intrafamily sequence
      comparisons of VL genes revealed additional diversity. Collectively, these
      studies confirm the existence of a third type of light chain gene in Xenopus,
      establish a high degree of genetic variation in the sequences encoding the light
      chain V regions, and provide the most significant evidence to date for the
      presence of a lambda-like light chain gene at the phylogenetic level of the
      amphibians.

PMID- 8759738
TI  - The rat MHC haplotype RT1c expresses two classical class I molecules.
AB  - Cloning and characterization of classical MHC class I coding sequences of the
      laboratory rat Rattus norvegicus has been reported so far for only four
      haplotypes, RT1a, RT1(1), RT1n, and RT1u. In all four cases, only one RT1.A
      classical class I molecule was found. Here we report that, in contrast, the RT1c
      haplotype expresses two different classical class I molecules. Using recombinant
      rat strains, we find that allotypic serologic determinants carried by the two
      molecules map to the RT1.A region, and so we have named them RT1.A1c and RT1.A2c.
      Multiple clones of functional cDNAs for each of these two molecules were isolated
      using a recently developed PCR-based expression-cloning method. Using a panel of
      20 RT1.Ac-reactive mAb, we find that six recognize RT1.A1c, seven recognize
      RT1.A2c, and seven recognize both. We also show that both molecules are
      recognized and distinguished by primary alloreactive cytotoxic T lymphocytes, and
      that they correspond to identifiable and distinct molecular species in cells that
      express RT1c naturally. These data all concur to demonstrate that the RT1.Ac
      region carries two different loci, each of which encodes a functional classical
      class I molecule.

PMID- 8759739
TI  - Stat1 alpha expression is involved in IFN-gamma induction of the class II
      transactivator and class II MHC genes.
AB  - Class II MHC Ags are critical in the regulation of immune responses by presenting
      Ag to T lymphocytes, resulting in their activation and differentiation. Class II
      expression is rare in the normal central nervous system, but elevated expression
      on glial cells has been observed in several neurologic diseases. We have
      previously demonstrated that IFN-gamma-induced class II expression in glial cells
      involves activation of both tyrosine kinase and protein kinase C. IFN-gamma
      induces tyrosine phosphorylation of the tyrosine kinases Jak1 and Jak2 and of
      Stat1 alpha. In addition, IFN-gamma enhances expression of Stat1 alpha mRNA and
      protein. We utilized antisense oligonucleotides against Stat1 alpha to determine
      directly whether IFN-gamma-induced activation and/or enhancement of Stat1 alpha
      is involved in class II expression. Antisense oligonucleotides complementary to
      Stat1 alpha mRNA were introduced in CH235-MG astroglioma cells by transient
      transfection; such treatment inhibited both constitutive and IFN-gamma-enhanced
      expression of Stat1 alpha. IFN-gamma-induced class II MHC expression was also
      inhibited in cells exposed to Stat1 alpha antisense oligonucleotides. The fact
      that the class II promoter does not contain IFN-gamma-activated sequences for
      binding Stat1 alpha suggests that Stat1 alpha must activate another protein that
      is directly involved in class II expression. A likely candidate is the class II
      MHC transactivator (CIITA). IFN-gamma induction of CIITA mRNA was also inhibited
      in cells treated with antisense oligonucleotides against Stat1 alpha. These
      findings demonstrate that Stat1 alpha is involved in IFN-gamma induction of CIITA
      expression, resulting in class II MHC expression.

PMID- 8759740
TI  - Comparison of CD45 extracellular domain sequences from divergent vertebrate
      species suggests the conservation of three fibronectin type III domains.
AB  - Mammalian CD45 is a transmembrane protein tyrosine phosphatase expressed by all
      nucleated cells of hematopoietic origin. In lymphocytes, CD45 is required for Ag
      induced signal transduction due to its ability to positively regulate Src family
      members. The mechanisms by which CD45 function is regulated are unknown. Indeed,
      the interactions of CD45 extracellular domains are largely undefined. To gain
      insight into potentially important regions of the extracellular domain, we sought
      to identify conserved features from divergent species. cDNAs encoding the
      putative CD45 homologue from Heterodontus francisci (horned shark) were isolated.
      The cDNA sequence predicts a protein of 1200 amino acids that contains a 452
      amino acid extracellular domain, a 22-amino acid transmembrane region, and a 703
      amino acid cytoplasmic domain. Alignment searches revealed that the Heterodontus
      cytoplasmic domain sequence was most identical to mammalian CD45 and a
      transmembrane protein tyrosine phosphatase sequence identified from chickens,
      ChPTP lambda. A dendrogram with other transmembrane protein tyrosine phosphatase
      sequences suggest that the Heterodontus and chicken sequences represents CD45
      orthologues for their respective species. Analysis of vertebrate CD45
      extracellular domain sequences indicates the conservation of three structural
      regions: a region containing potential O-linked carbohydrate sites, a cysteine
      containing region, and a region containing three fibronectin type III domains.
      For each vertebrate species, multiple isoforms are generated by alternative
      splicing of three exons that encode a portion of the region containing potential
      O-linked glycosylation sites. These studies provide evidence for a conservation
      in CD45 extracellular domain structure between divergent species and provide a
      basis for understanding CD45 extracellular domain interactions.

PMID- 8759741
TI  - The binding epitopes of human CD16 (Fc gamma RIII) monoclonal antibodies.
      Implications for ligand binding.
AB  - Numerous mAbs have been generated against Fc gamma RIII (CD16), the low-affinity
      receptor for the Fc part of IgG. Most of the mAbs recognize both the receptor
      isoforms, transmembranous Fc gamma RIIIA, and glycosylphosphatidylinositol-linked
      Fc gamma RIIIB. Binding epitopes of some of the mAbs that differentiate between
      the two neutrophil Ag (NA) alleles of Fc gamma RIIIB (CLB-Gran11 against NA1;
      GRM1, BL-LGL/1 against NA2 allele) have been mapped on the first, membrane-distal
      domain of CD16. We demonstrate that mAbs 3G8, B88-9, CLB-Gran1, MEM-154, and
      LNK16 almost completely block the receptor's interaction with IgG. Using chimeric
      Fc gamma RIIIB/Fc epsilon RI receptors and molecular modeling, we localized the
      epitopes of 3G8 and B88-9 on the putative FG loop of the membrane-proximal Ig
      like domain, which we have previously identified as the major binding site for
      IgG. The epitopes of CLB-Gran1 and MEM-154 are shown to reside in proximity to
      the FG loop (probably BC or C'E loop). The blocking mAb LNK16 was detected to be
      directed against the putative C' beta-sheet of the membrane-proximal domain,
      suggesting that additional residues may be involved in IgG binding of Fc gamma
      RIII.

PMID- 8759742
TI  - Characterization of an Ig VH idiotope that results in specific homophilic binding
      and increased avidity for antigen.
AB  - mAb against GD3 ganglioside demonstrate homophilic binding in which soluble anti
      GD3 mAb bind, through the GD3 binding site, to a VH idiotope (designated IdHOM)
      on solid phase anti-GD3 mAb. In this way, homophilic binding provides a mechanism
      for amplifying the binding of mAb to cell surface GD3. We show that serine 52a,
      within CDR2, is required for IdHOM expression, homophilic binding, and high
      avidity binding to cell surface GD3. Computer modeling based on the crystal
      structure of anti-GD3 mAb R24 showed serine 52a situated at the mouth of the GD3
      binding pocket, but not directly involved with GD3 binding. Substitutions at
      position 52a predicted to maintain the GD3 binding pocket (e.g., threonine)
      resulted in the loss of IdHOM expression and homophilic binding and markedly
      decreased binding to cell surface GD3, but maintained low avidity GD3 binding as
      measured by ELISA. All other substitutions at position 52a were predicted to
      significantly distort the GD3 binding pocket and resulted in the loss of both
      homophilic binding and any detectable avidity for GD3. We have structurally
      defined IdHOM and conclude that this idiotope is not required for the GD3 binding
      pocket, but that the idiotope is necessary for homophilic binding, which is
      required for high avidity binding to cell surface GD3. We speculate that
      selection of certain VH genes may result in the expression of idiotopes that
      allow homophilic binding, and this may represent a general mechanism for
      increasing the avidity of Abs against T cell-independent Ags.

PMID- 8759743
TI  - IL-12 is both required and sufficient for initiating T cell reactivity to a class
      I-restricted tumor peptide (P815AB) following transfer of P815AB-pulsed dendritic
      cells.
AB  - Delayed-type hypersensitivity responses, mediated by CD8+ cells and detected by
      skin test assay, occur in sensitized mice in response to challenge with a class I
      restricted synthetic peptide related to a poorly immunogenic tumor rejection Ag,
      P815AB, of murine mastocytoma cells. Efficient priming for this response, which
      requires functional CD4+ cells and production of IFN-gamma in the host, is
      achieved by transfer of dendritic cells (DC) pulsed in vitro with a physical
      mixture of P815AB and T helper peptides, such as a class II-restricted synthetic
      peptide of tetanus toxin. We now show that the adjuvant effect of the T helper
      peptide was associated with the appearance of early and late IL-12 transcripts in
      the spleens of DC recipient mice, correlated with a late IFN-gamma response, and
      was negated by serologic ablation of endogenous IL-12 at the time of cell
      transfer. rIL-12, administered in vivo to the DC recipient mice, could substitute
      for the T helper peptide in initiating skin test reactivity following transfer of
      DC pulsed with P815AB alone, leading to Ag-specific production of IFN-gamma by
      CD4+ and CD8+ T cells. In vitro and in vivo cell depletion experiments suggested
      the following: 1) the exogenous IL-12 required both CD4+ and CD8+ cells for
      activity; 2) the immune response initiated by IL-12 relied on later production of
      IL-12 by the host; and 3) the early adjuvanticity of the exogenous IL-12 involved
      improved recognition of class II-restricted epitopes of this otherwise poorly
      immunogenic tumor peptide.

PMID- 8759744
TI  - Th1-associated immune responses to beta-galactosidase expressed by a replication
      defective herpes simplex virus.
AB  - The immunogenic properties of a replication-defective herpes simplex virus HD-2,
      containing the Escherichia coli lacZ gene under control of the HSV ICP8 early
      gene promoter were studied in BALB/c mice. Experiments were designed to determine
      if the HD-2 virus preferentially stimulated either Th1- or Th2-associated immune
      responses to beta-galactosidase (beta gal). Sera from mice immunized i.p. or s.c.
      with virus HD-2, beta gal on aluminum phosphate adjuvant, or a control ICP8
      deletion mutant, d301, were assayed for total and Ag-specific IgG1 and IgG2a Abs,
      beta gal-driven lymphocyte proliferation, and in vitro production of the
      cytokines IFN-gamma, IL-4, and IL-2. Viruses HD-2 and d301 preferentially
      stimulated the production of total serum IgG2a following two immunizations i.p.
      or a single immunization s.c., while only HD-2 virus stimulated in vivo
      production of beta gal-specific IgG2a serum Abs. In contrast, beta gal adsorbed
      on AIPO4 preferentially stimulated production of Ag-specific IgG1 serum Abs. The
      HD-2 virus also induced a potent cellular proliferative response to beta gal,
      which was still pronounced 5 wk after primary immunization. Cultured lymphocytes
      from HD-2-immunized mice produced IFN-gamma after 5 days in culture with soluble
      beta gal in an Ag- and dose-dependent fashion. These results demonstrate that
      replication-defective mutants of HSV can be used as vectors for eliciting Th1
      associated immune responses to a heterologous Ag expressed from the viral genome.

PMID- 8759745
TI  - Rhinovirus produces nonspecific activation of lymphocytes through a monocyte
      dependent mechanism.
AB  - There is evidence that rhinovirus (RV) infections are frequent causes of
      increased asthmatic symptoms and can specifically enhance allergic inflammation
      in the airway. To further define effects of RV infection on cellular immunity, we
      have begun to develop in vitro models for study. When human PBMC were incubated
      with 35S-labeled RV16, specific binding via ICAM-1 on monocytes was observed.
      Incubation of PBMC with RV also led to a dose-related increase in the expression
      of the early activation marker CD69 on 30 to 70% of T cells. The RV16-induced
      increases in CD69 were blocked by anti-ICAM-1 mAb, and were not elicited by UV
      inactivated (noninfectious) virus. The degree of CD69 enhancement correlated with
      the number of monocytes in mixtures of PBMC, did not occur in monocyte-depleted
      cultures, and was mediated by one or more soluble factor(s). RV also induced
      secretion of IFN-gamma from both peripheral blood T cells and NK cells, and IFN
      gamma mRNA was greatest in T cells that were CD69+. Finally, supernatant from RV
      activated CD3+CD69+ cells had biologic activity that promoted eosinophil survival
      in vitro; this RV16-associated activity was blocked when co-incubations were
      performed with IFN-gamma mAbs. These observations suggest that RV nonspecifically
      activates a large proportion of T cells through a monocyte-dependent mechanism.
      Such changes in vivo could enhance airway inflammation, and this may include
      effects on inflammatory cells in the airways of allergic individuals.

PMID- 8759746
TI  - Escherichia coli and Pseudomonas aeruginosa induce expansion of V delta 2 cells
      in adult peripheral blood, but of V delta 1 cells in cord blood.
AB  - Human peripheral blood T cells proliferate in response to Escherichia coli and
      Pseudomonas aeruginosa. We observed that during the first few days after
      stimulation a large percentage of the responding PBMC were gamma delta T cells.
      In our study we characterized the early T cell responses of freshly isolated
      adult and newborn PBMC to soluble preparations of heat-killed E. coli and P.
      aeruginosa. Specimens from all healthy adults tested showed intense proliferation
      in response to both bacterial preparations; at 6 days, the responding cells were
      mainly T cell blasts, of which high percentages (up to 80%) were gamma delta T
      cells, most expressing V delta 2/V gamma 9. All newborn blood specimens tested
      also showed T cell proliferative responses, which included a marked expansion of
      gamma delta T cells, mainly of the V delta 1 subset. Populations of purified V
      delta 1 and V delta 2 T cells were obtained from adult PBMC following stimulation
      with E. coli; both subsets proliferated upon rechallenge with the bacterial
      preparations. Protease treatment of the bacterial preparations did not
      appreciably affect their ability to induce expansion of gamma delta T cells in
      either adult or cord blood, indicating that the stimulatory components were not
      proteins. The response of gamma delta T cells from newborns indicates that prior
      exposure to bacterial products is not necessary and suggests that gamma delta T
      cells are important elements in natural immunity to these extracellular
      organisms.

PMID- 8759747
TI  - Participation of lymphocyte subpopulations in the pathogenesis of experimental
      murine cerebral malaria.
AB  - We determined the requirement for selected lymphocyte subsets and cytokines in
      the pathogenesis of experimental murine cerebral malaria (CM) by using gene
      targeted knockout and mAb-suppressed mice. Plasmodium berghei ANKA infection
      induced CM in A 0/0 mice, which lack expression of surface MHC class II
      glycoproteins and consequently express a severe and chronic reduction in numbers
      of CD4+ T cells. However, when A 0/0 mice, which are on a C57BL/6 x 129 genetic
      background, or immune-intact C57BL/6 controls treated with anti-CD4 mAb were
      infected, none developed CM. The latter finding confirms an earlier report that
      CD4+ T cells are required for CM to occur and additionally indicates that the
      reduced numbers of CD4+ T cells present in A 0/0 mice are sufficient for CM
      development. Neither the recently described CD4+, NK1.1+ T cell subset shown to
      be present in A 0/0 mice nor traditional NK cells seem to be required for the
      induction of CM because A 0/0 and C57BL/6 mice severely depleted of both NK1.1+
      populations with mAb developed CM as readily as did normal Ig-treated controls.
      Deficiency of Th1-associated cytokines (IFN-gamma or IL-2) in mice by gene
      targeted disruptions completely inhibited CM development, whereas the lack of Th2
      associated cytokines (IL-4 or IL-10) did not prevent this disease. Our
      observation that B cell-deficient JHD and microMT mice developed CM provides
      evidence that neither B cells, their products, nor B cell Ag presentation are a
      requisite for CM pathology. We further observed that neither beta 2m 0/0 knockout
      mice, which lack CD8+ alpha beta T cells, nor C57BL/6 mice depleted of CD8+ T
      cells with anti-CD8 mAb treatment developed CM, leading us to conclude that CD8+
      T cells are also crucial for the development of CM.

PMID- 8759748
TI  - Enhancement of TNF-alpha synthesis by overexpression of G alpha z in a mast cell
      line.
AB  - Ag stimulation of mast cells via the IgE receptor (Fc epsilon RI) elicits
      production and release of numerous cytokines. This activation of Fc epsilon RI
      initiates various tyrosine kinase-dependent signaling cascades, which ultimately
      result in the de novo synthesis of cytokines. To date, no heterotrimeric G
      proteins have been implicated in this process. Here we report that the alpha
      subunit of the heterotrimeric G protein, Gz, can regulate production of the
      cytokine, TNF-alpha. The alpha subunit was overexpressed in a cultured mast cell
      line (RBL-2H3) known to contain G alpha z. In stimulated cells, overexpression of
      G alpha z significantly enhanced the production of TNF-alpha. This effect of G
      alpha z appeared to be restricted in that constitutive synthesis of the cytokine,
      TGF-beta, and Ag-stimulation of the phosphoinositide-dependent secretory pathway
      were not significantly affected. Thus, G alpha z, a heterotrimeric G protein,
      appeared to modulate the stimulatory pathways for induction of TNF-alpha
      synthesis in RBL-2H3 cells.

PMID- 8759749
TI  - In vivo antioxidant treatment suppresses nuclear factor-kappa B activation and
      neutrophilic lung inflammation.
AB  - We hypothesized that endotoxin injection in rats would stimulate in vivo nuclear
      factor-kappa B (NF-kappa B) activation in lung tissue and that antioxidant
      treatment before endotoxin injection would attenuate endotoxin-induced NF-kappa B
      activation, chemokine gene expression, and neutrophilic lung inflammation. We
      studied NF-kappa B activation in rat lung tissue following a single i.p.
      injection of endotoxin (6 mg/kg). After in vivo endotoxin treatment, lung NF
      kappa B activation peaked at 2 h and temporally correlated with the expression of
      cytokine-induced neutrophil chemoattractant mRNA in lung tissue. Treatment with
      the antioxidant N-acetylcysteine (NAC) 1 h before endotoxin resulted in decreased
      lung NF-kappa B activation in a dose-dependent manner (from 200-1000 mg/kg) and
      diminished cytokine-induced neutrophil chemoattractant mRNA expression in lung
      tissue. Treatment with NAC significantly suppressed endotoxin-induced
      neutrophilic alveolitis. The average total lung lavage neutrophil count was 5.5 x
      10(6) with endotoxin treatment vs 0.9 x 10(6) with NAC treatment before
      endotoxin. The NF-kappa B pathway represents an attractive therapeutic target for
      strategies to control neutrophilic inflammation and lung injury.

PMID- 8759750
TI  - Stress-induced changes in blood leukocyte distribution. Role of adrenal steroid
      hormones.
AB  - The numbers and proportions of leukocytes in the blood provide an important
      representation of the state of activation of the immune system, and of the
      pattern of distribution of immune cells in the body. We have shown previously
      that acute stress induces large, rapid, and reversible changes in the
      distribution of peripheral blood leukocyte subpopulations in the rat. The studies
      described here specifically investigate the role played by adrenal steroid
      hormones in mediating stress-induced changes in blood leukocyte distribution.
      Since adrenal steroids act at two distinct receptor subtypes that show a
      heterogeneity of expression in immune cells and tissues, the role played by each
      subtype in mediating changes in leukocyte distribution is also investigated.
      Cyanoketone, a corticosterone (CORT) synthesis inhibitor, significantly reduced
      the decrease in lymphocyte numbers observed during stress and significantly
      enhanced the increase in neutrophil numbers observed after the cessation of
      stress. Acute administration of aldosterone (a specific type I adrenal steroid
      receptor agonist) to adrenalectomized animals did not have a significant effect
      on blood leukocyte numbers. In contrast, acute administration of CORT (the
      endogenous type I and type II receptor agonist), or RU28362 (a specific type II
      receptor agonist), to adrenalectomized animals produced changes in leukocyte
      distribution that were similar to those observed in intact animals during stress.
      These results suggest that CORT, acting at the type II adrenal steroid receptor,
      is a major mediator of the stress-induced changes in blood lymphocyte and
      monocyte distribution.

PMID- 8759751
TI  - Anaphylaxis mediated through a humanized high affinity IgE receptor.
AB  - Mast cells and basophils, which are activated by IgE and allergens through the
      high affinity IgE receptor (Fc epsilon RI), play a prominent role in anaphylaxis
      in the mouse. Mice deficient in this receptor become resistant to passive
      anaphylaxis. As a first step in developing an in vivo model that more closely
      mimics the IgE-mediated responses in man, we used a combination of transgenic and
      embryonic stem cell technology to generate a mouse line in which the murine Fc
      epsilon RI alpha-chain has been replaced with its human homologue. We demonstrate
      here that these mice express a tetrameric high affinity IgE receptor, in which
      the human alpha-chain associates with the murine beta- and gamma-chains, and that
      upon triggering with relevant Ag, this receptor mediates the initiation of the
      expected intracellular events. In addition, we show that the human alpha-chain
      restores an anaphylactic response to the nonresponsive alpha-deficient parental
      mouse line. This "humanized" mouse represents a potentially important model
      system, not only for studying the role of IgE in human immune responses, but also
      for testing potential therapeutic reagents that can interfere with responses
      mediated through the human Fc epsilon RI receptor.

PMID- 8759752
TI  - Cytokine activation sensitizes human monocytic and endothelial cells to the
      cytotoxic effects of an anti-CD40 immunotoxin.
AB  - G28-5 sFv-PE40 is a single-chain immunotoxin that is cytotoxic toward malignant B
      cells expressing CD40. Human monocytes, which also express cell surface CD40,
      were found to be insensitive to the immunotoxin. Activation of the monocytic cell
      line THP-1, or freshly isolated peripheral blood monocytes with IFN-gamma, but
      not IL-3, GM-CSF, IL-6, or TNF-alpha, greatly sensitized the cells toward G28-5
      sFv-PE40, lowering the EC50 value from > 10 micrograms/ml to 80 ng/ml. This
      sensitization could not be explained simply by the two- to threefold increase in
      cell surface CD40 expression induced by IFN-gamma since TNF-alpha or the
      combination of TNF-alpha and IL-6 gave similar increases in CD40 expression but
      did not sensitize the cells to the immunotoxin. Internalization of G28-5 sFv-PE40
      after IFN-gamma activation was also increased threefold, reflective of the
      increase in CD40 expression. IFN-gamma-treated but not -untreated THP-1 cells
      produced IL-6 and TNF-alpha following incubation with G28-5 sFv-PE40, indicating
      an association between CD40 signaling, which induces cytokine production, and
      sensitivity to the immunotoxin. HUVECs also express CD40 but were found to be
      insensitive to the anti-CD40 immunotoxin. A combination of IFN-gamma and TNF
      alpha, but neither cytokine alone, sensitized the endothelial cells to G28-5 sFv
      PE40. These data show that activation with cytokines can sensitize monocytes and
      endothelial cells to an immunotoxin targeted to CD40, most likely by altering the
      trafficking and/or processing of the immunotoxin after receptor-mediated
      internalization.

PMID- 8759753
TI  - Analysis of the gene that encodes the complement regulatory protein, membrane
      inhibitor of reactive lysis (CD59). Identification of an alternatively spliced
      exon and characterization of the transcriptional regulatory regions of the
      promoter.
AB  - Membrane inhibitor of reactive lysis (MIRL, CD59) is an 18-kDa
      glycosylphosphatidylinositol-anchored protein that regulates formation of the
      membrane attack complex of complement. The purpose of these studies was to
      characterize the gene that encodes CD59. Our experiments redefined the structural
      organization of the gene by identifying a previously unrecognized alternatively
      spliced exon. Analysis by PCR of cDNA derived from a variety of cultured human
      cell lines and from PBMC showed that transcripts containing the alternatively
      spliced exon sequence were expressed concordantly with transcripts lacking that
      sequence. Primer extension studies demonstrated that the transcriptional start
      site of alternatively spliced CD59 mRNA is the same as that of transcripts
      without the alternatively spliced exon sequence, suggesting that expression of
      both forms of CD59 mRNA is regulated similarly. Analysis of the promoter region
      showed that the first 70 nucleotides immediately 5' of the transcriptional start
      site of the CD59 gene are essential for both constitutive and PMA-responsive
      transcription; however, responsiveness to PMA is cell line specific. Together,
      these studies have redefined the organization of the CD59 gene and identified
      regions of the promoter involved in constitutive and PMA-inducible transcription.

PMID- 8759754
TI  - Phospholipase A2 triggers the first phase of the thermal stress response and
      exhibits cell-type specificity.
AB  - To understand the relationship of inflammatory and cellular stress responses,
      phospholipase A2 (PLA2) was examined for its role in the first phase of the
      transcriptional response to cellular stress. Electromobility shift analysis
      revealed heat shock transcription factor (HSF1)-DNA binding when HeLa S3 and
      Jurkat cells were exposed to exogenous PLA2. Although PLA2-inducible HSF1-DNA
      binding was comparable to thermal stress, it did not induce maximal heat shock
      gene expression. PLA2-induced HSF1 was not hyperphosphorylated relative to the
      heat-inducible form, thus suggesting that exogenous PLA2 affects the signal for
      HSF1 multimerization but not its phosphorylation. Because inflammation often
      involves elevated temperatures, the effect of PLA2 on thermal regulation of HSF1
      DNA binding activity was examined. PLA2 exposure altered the thermal threshold
      for HSF1 activation, and pore-gradient gel analysis indicated that either
      conformational changes or other modifications of HSF1 are being induced when
      cells are treated by PLA2, thus creating a synergistic environment for HSF1
      activation into its DNA-bound state. Surprisingly, the monocyte-like cell line, U
      937, was insensitive to the action of exogenous PLA2. Neither HSF1-DNA binding or
      lowering of the temperature threshold for HSF1 activation was observed in PLA2
      treated U-937 cells. These data suggest that inflammatory mediators such as PLA2
      partially affect transcriptional switches mediating thermal stress in some cell
      types but not others. The purpose of HSF1 activation during inflammation and its
      differential induction are discussed relative to these observations.

PMID- 8759755
TI  - Activation of human eosinophils by IL-13. Induction of CD69 surface antigen, its
      relationship to messenger RNA expression, and promotion of cellular viability.
AB  - To study the effect of IL-13 on CD69 expression and cell viability in human
      eosinophils, purified human peripheral blood eosinophils from healthy donors were
      incubated with increasing concentrations of IL-13. The expression of CD69 was
      analyzed by flow cytometry (FACS). Surface expression of CD69, which was absent
      on untreated eosinophils, was induced by IL-13 at concentrations ranging from 1
      ng/ml to 1 microgram/ml in a concentration-dependent manner. In contrast,
      neutrophils expressed CD69 neither spontaneously nor following incubation with IL
      13. Semiquantitative reverse transcription-PCR for CD69 mRNA showed constitutive
      CD69 mRNA expression in purified human eosinophils. Incubation of eosinophils
      with IL-13 further increased CD69-specific mRNA. Analysis of intracellularly
      stored CD69 in eosinophils permeabilized with saponin revealed intracellular
      binding of anti-CD69 Abs in all isolated eosinophils. After stimulation with 100
      ng/ml IL-13 for 24 h, the concentration of intracellular CD69 decreased by 41 +/-
      9%. Furthermore, IL-13 at a concentration of 100 ng/ml enhanced eosinophil
      viability, as assessed by propidium iodide staining after 4 days in culture from
      8.6 +/- 5.5% in control medium to 50.7 +/- 6.8% following stimulation with IL-13
      treatment. The effect of Il-13 on eosinophil viability as well as that on CD69
      expression were both neutralized by anti-IL-13 Abs. In conclusion, our results
      demonstrate that IL-13 specifically activates human eosinophils, as determined by
      the expression of CD69 cell surface protein and mRNA expression. Furthermore, IL
      13 significantly prolongs eosinophil survival in vitro. The data suggest that IL
      13 may play a role in the activation of eosinophils.

PMID- 8759756
TI  - Priming of eosinophil recruitment in vivo by LPS pretreatment.
AB  - Eosinophils are important inflammatory cells in allergic diseases. Recent
      evidence suggests that priming mechanisms in the blood may be important for
      effective eosinophil recruitment to sites of allergic inflammation. We have
      investigated whether priming an inflammatory site could enhance eosinophil
      recruitment in vivo. Pretreatment of skin sites in the guinea pig with a low dose
      (30 ng) of LPS, which had little effect on eosinophil accumulation alone,
      enhanced by up to threefold the 111In-eosinophil accumulation in response to a
      passive cutaneous anaphylactic reaction and to intradermally injected eosinophil
      chemoattractants (leukotriene B4, PAF, and C5ades Arg). In contrast, LPS
      pretreatment did not enhance accumulation of 111In-neutrophils. Priming was seen
      only with a 1-h pretreatment time and was not associated with an increase in
      local edema or a change in cutaneous blood flow. It was independent of local
      protein synthesis, as assessed using cycloheximide, and was unaffected by a PAF
      antagonist, a 5-lipoxygenase inhibitor, and the IL-1 receptor antagonist. The
      priming response was, however, reduced by co-injection with the LPS of TNFR-IgG,
      but not of CD4-IgG. Blockade of CD18 showed this adhesion molecule to be critical
      for eosinophil accumulation, and LPS-primed sites were inhibited as effectively
      as nonprimed sites. In conclusion, low dose LPS pretreatment of guinea pig skin
      sites primes for eosinophil accumulation induced by intradermally injected
      inflammatory mediators and cutaneous anaphylactic reaction. This may be an
      important process by which eosinophil recruitment is modulated in vivo.

PMID- 8759757
TI  - C3a and C5a are chemotaxins for human mast cells and act through distinct
      receptors via a pertussis toxin-sensitive signal transduction pathway.
AB  - Mast cells are known to accumulate at sites of inflammation, however, the
      chemotaxins involved are undefined. Since most natural leukocyte secretagogues
      also induce cell migration, and since the anaphylatoxins C3a and C5a are mast
      cell secretagogues, we hypothesized that both C3a and C5a are also mast cell
      chemotaxins. Here we report that C3a and C5a are, in fact, potent chemotaxins for
      the human mast cell line HMC-1. The optimal concentrations, half-maximal
      effective concentrations (a measure of agonist potency) and the efficacy
      (response at the optimal concentration) compared with medium control were, for
      C3a: 10 nM, 0.5 nM, and 256%, respectively; for C5a: 1 nM, 10 pM and 145%.
      Chemotaxis of HMC-1 cells to both C3a and C5a was blocked by pertussis toxin,
      suggesting that Gi-coupled receptors are involved in signal transduction. C3a and
      C5a also induced transient pertussis toxin-inhibitable increases in [Ca2+]i (ED50
      = 1 nM for both) that could be homologously but not heterologously desensitized,
      suggesting that the receptors for C3a and C5a are distinct. These results make
      C3a the most effective mast cell chemotaxin identified to date. The chemotactic
      potency described here for C3a is also 100- to 1000-fold greater than for all of
      its previously described cellular actions. Direct chemoattraction of mast cells
      by C3a and C5a may help explain the rapid accumulation of mast cells at sites of
      inflammation.

PMID- 8759758
TI  - IL-1 beta activation in human epidermis.
AB  - IL-1 beta is produced as an inactive 31-kDa precursor processed to active 18-kDa
      IL-1 beta by proteolytic cleavage, catalyzed by the highly specific IL-1
      converting enzyme (ICE). In vitro activation of IL-1 beta can also be obtained by
      other proteases. Human keratinocytes express IL-1 beta, but not active ICE. The
      role played by IL-1 beta produced by keratinocytes has therefore been unclear. We
      asked whether normal human plantar stratum corneum contains biologically active
      IL-1 beta and, if so, by which mechanism this IL-1 beta is activated. Crude
      extracts and partially purified preparations from which IL-1 alpha had been
      removed were used. Biologic IL-1 activity was measured as the ability to induce
      expression of E-selectin in HUVEC. The crude extract contained IL-1-like activity
      that could be partially abolished with Abs to IL-1 alpha or IL-1 beta and totally
      inhibited with a mixture of the two Abs. IL-1 activity in the partially purified
      preparation was totally inhibited by Abs to IL-1 beta. The specific IL-1 beta
      activity in the two preparations was 60 to 85% of the sp. act. of recombinant
      human IL-1 beta. IL-1 beta from plantar stratum corneum had a slightly higher
      molecular mass than recombinant mature IL-1 beta. Its isoelectric point was
      approximately 6.1 compared with 6.9 for rIL-1 beta. We conclude that human
      plantar stratum corneum contains biologically active IL-1 beta that has been
      activated by an alternative mechanism that does not involve ICE. This is, to our
      knowledge, the first report of an alternative mechanism of IL-1 beta activation
      occurring in vivo.

PMID- 8759759
TI  - IL-11 enhances survival and decreases TNF production after radiation-induced
      thoracic injury.
AB  - We hypothesized that IL-11 would protect against radiation-induced thoracic
      injury. To test this hypothesis, we compared the survival of rIL-11 and vehicle
      treated control mice after 25 Gy of thoracic irradiation, and initiated studies
      to elucidate the mechanism of the observed protection. This dose of radiation
      killed 50% of the control mice during the first 2 wk after irradiation. In
      contrast, the s.c. administration of rIL-11 resulted in significant
      radioprotection with 89% of the rIL-11-treated animals surviving the study
      interval (p < 0.001). This radioprotection was at least partially specific for
      normal thoracic structures since rIL-11 did not alter the development or
      radiosensitivity of EMT6 tumor cells growing as lung metastases. TNF mRNA was not
      detected in normal lungs but was impressively induced after thoracic irradiation.
      Treatment with rIL-11 abrogated this increase. Parallel in vitro studies
      demonstrated that rIL-11 inhibits LPS and radiation-induced macrophage TNF
      protein production and mRNA accumulation. These studies demonstrate that rIL-11
      reduces the mortality following thoracic irradiation, without enhancing the
      development or diminishing the radiosensitivity of pulmonary metastatic tumors.
      They also demonstrate that rIL-11 inhibits both radiation-induced TNF mRNA
      expression in vivo and macrophage TNF protein production and mRNA accumulation in
      vitro, suggesting that the radioprotective effects of rIL-11 may be mediated, at
      least in part, via the modulation of TNF production.

PMID- 8759760
TI  - Functional and structural characterization of the eosinophil P-selectin ligand.
AB  - Our recent studies have indicated an important role for P-selectin in eosinophil
      adhesion. We have therefore compared eosinophil and neutrophil binding with nasal
      polyp endothelium as well as purified P-selectin. We have also compared the
      structure and expression of the eosinophil and neutrophil P-selectin ligands.
      Using the frozen section assay, eosinophils bound to 2-fold more blood vessels
      within the nasal polyp tissue than neutrophils. Up to 10-fold more eosinophils
      than neutrophils bound per unit length of endothelium. Neutrophil and eosinophil
      binding was inhibited by a mAb against P-selectin and a P-selectin chimera which
      binds to the P-selectin ligand. Eosinophils bound with approximately 2-fold
      greater avidity to purified P-selectin under flow conditions. Using SDS-PAGE we
      characterized the eosinophil P-selectin ligand as a sialylated, homodimeric
      glycoprotein consistent with the known structure of PSGL-1. However, expression
      of PSGL-1 by eosinophils was significantly greater than on neutrophils. The
      eosinophil ligand had a calculated molecular mass by SDS-PAGE of approximately 10
      kDa greater than the neutrophil ligand, which was not due to differences in N
      glycosylation. Eosinophils expressed the 15-decapeptide repeat form of PSGL-1
      compared with neutrophils that have the 16-decapeptide repeat form. The increased
      binding of eosinophils, compared with neutrophils, to P-selectin in both an ex
      vivo and in vitro assay suggests that P-selectin may have a role directing the
      specific migration of eosinophils in diseases such as asthma. The increased
      avidity may be due to increased expression of PSGL-1 by eosinophils, differences
      in the peptide backbone, or post-translational modifications.

PMID- 8759761
TI  - Mouse bone marrow-derived mast cells and mast cell lines constitutively produce B
      cell growth and differentiation activities.
AB  - The present report describes a novel function of mast cells that consists of a B
      cell growth activity. The B cell response occurred without any stimulation or
      preactivation of mast cells. A small number of mast cells was required, since
      mast cell/B cell ratios as low as 1/100 to 1/10,000 lead to effective B cell
      activation. Mast cell-dependent B cell activation resulted, within 48 h of
      incubation, in blast formation, proliferation, and IgM production. Both low and
      high density B cells were responsive to mast cells. Supernatants from
      unstimulated mast cells could also activate B cells, suggesting that a B cell
      stimulating activity (MC-BSA) is mediated by a soluble factor(s). The addition of
      anti-IL-4 or anti-IL-6 mAbs or even proteases to the mast cell-derived
      supernatants did not alter B cell activation. However, treatment of mast cells
      with mitomycin C or actinomycin D, or paraformaldehyde fixation totally abrogated
      MC-BSA. Fractionation of mast cell supernatant by gel filtration chromatography
      resulted in four peaks, ranging from > 200 to 15 kDa, all of which were
      biologically active on B cells. Because mast cells are known to continuously
      release proteoglycans, MC-BSA was subjected to chondroitinase and heparinase
      treatment, but no significant inhibition of B cell activation was obtained. This
      direct T cell-independent stimulatory effect of mast cells on B cells could
      account for a mechanism by which plasma cells are continuously produced in
      lymphoid organs and particularly in bone marrow.

PMID- 8759762
TI  - CD88 antibodies specifically bind to C5aR on dermal CD117+ and CD14+ cells and
      react with a desmosomal antigen in human skin.
AB  - The expression of the C5aR (CD88) on human epidermal and dermal cells was studied
      with five anti-C5aR mAb directed to the N-terminal domain of the receptor. All
      mAb bound to suspended dermal CD117+ mast cells and to dermal CD14+ cells. The
      binding to CD14+ and CD117+ cells could be blocked by rC5a and by peptide EX-1
      representing amino acid residues 1-31 of the C5aR. In acetone-fixed frozen or in
      paraformaldehyde-fixed, paraffin-embedded tissue, we detected a binding of the
      Abs to dermal perivascular cells and, additionally, to keratinocytes and dermal
      epithelial cells that could be blocked by EX-1. Immunoelectromicroscopy revealed
      a binding of anti-C5aR mAb to desmosomal regions in human epidermis. However, the
      following results indicate that CD88 mAb cross-react with epithelium in a
      specific way: 1) the binding to suspended epidermal cells and to the epidermal
      cell line HaCat could be blocked by EX-1 but not by rC5a; 2) FITC-labeled C5a
      bound to CD117+ and to CD14+ cells but not to epidermal cells; 3) C5a led to
      transient calcium fluxes in CD14+ and CD117+ dermal but not in epidermal cells;
      4) C5aR mRNA was detectable by reverse transcription PCR in granulocytes but not
      in keratinocytes or in HaCat. Our results show that CD88 mAb are good tools for
      the investigation of the C5aR on hemopoietic cells. Results with epithelial cells
      should be considered with caution, as the binding of CD88 mAb that were raised to
      a synthetic peptide sequence may be due to a cross-reactivity.

PMID- 8759763
TI  - Identification of mouse granulocyte chemotactic protein-2 from fibroblasts and
      epithelial cells. Functional comparison with natural KC and macrophage
      inflammatory protein-2.
AB  - Neutrophil and monocyte chemotactic factors were isolated from conditioned media
      of mouse fibroblasts and epithelial cells. Neutrophil chemotactic activities were
      purified to homogeneity using a four-step chromatographic procedure, and the
      corresponding proteins were identified by amino acid sequence analysis. Natural
      forms of the murine chemokines KC and macrophage inflammatory protein-2 were
      isolated from virus-infected fibroblasts. However, the major neutrophil
      chemotactic activity from fibroblasts stimulated with endotoxin plus double
      stranded RNA and from PMA-treated epithelial cells resided in other 7- and 8-kDa
      proteins. Amino acid sequence analysis revealed a novel Cys-Xaa-Cys chemokine
      structure, characterized by the conservation of four cysteines and the Glu-Leu
      Arg motif. Based on the completely identified primary structure of this natural
      protein, this chemokine must be considered to be the murine homologue of human
      and bovine granulocyte chemotactic protein-2 (GCP-2; 61 and 64% identical
      residues, respectively). Due to NH2-terminal cleavage, 11 different forms of
      mouse GCP-2 were discovered. In contrast to human and bovine GCP-2, functional
      comparison of long and short NH2-terminal forms of mouse GCP-2 demonstrated that
      truncated mouse GCP-2 (short form) has a higher specific activity in neutrophil
      activation (gelatinase B release) and chemotaxis assays. Furthermore, mouse GCP-2
      was more potent than human GCP-2 on human neutrophils, and more active than
      murine KC and macrophage inflammatory protein-2 on mouse neutrophils. In view of
      the absence of a murine homologue for IL-8, NH2-terminally processed GCP-2 can be
      considered a major neutrophil chemoattractant in the mouse during the
      inflammatory response.

PMID- 8759764
TI  - Role of vitamin D3-binding protein in activation of mouse macrophages.
AB  - When mouse peritoneal nonadherent (lymphocytes) cells were treated with
      lysophosphatidylcholine (lyso-Pc) and cultured with adherent cells (macrophages)
      in 1% fetal calf serum (FCS)- or adult mouse serum (AMS)-supplemented medium for
      3 h, markedly enhanced phagocytic and superoxide-generating capacities of
      macrophages were observed. Stepwise cultivation of lyso-Pc-treated B cells and
      untreated T cells with an FCS-supplemented medium generated a macrophage
      activating factor (MAF), whereas cultivation of lyso-Pc-treated B cells alone in
      AMS-supplemented medium was sufficient to generate the MAF. The accumulated
      evidence suggests that lyso-Pc-inducible beta-galactosidase of B lymphocytes and
      the Neu-1 sialidase of T lymphocytes modified the bovine serum vitamin D3-binding
      protein (DBP) to yield the MAF, a protein with N-acetylgalactosamine as the
      remaining sugar. In contrast, the lyso-Pc-inducible beta-galactosidase of B cells
      alone modified mouse DBP to yield the MAF. These observations led us to conclude
      that bovine DBP carries a trisaccharide composed of N-acetylgalactosamine,
      galactose, and sialic acid, whereas mouse DBP carries a disaccharide composed of
      N-acetylgalactosamine and galactose. Thus, macrophages of a T-cell-deficient nude
      (BALB/c nu/nu) mouse and a T-cell Neu-1 sialidase-deficient SM/J mouse were
      efficiently activated by administration of lyso-Pc.

PMID- 8759765
TI  - Induction of autoimmunity in the absence of CD28 costimulation.
AB  - Ag-specific activation of T lymphocytes requires two signals, one by the TCR and
      a second by costimulatory molecules. In a CD4+ T helper cell-dependent
      experimental autoimmune myocarditis model, we provide genetic evidence that
      cardiac myosin-induced autoimmune myocarditis and the production of IgG auto-Abs
      is dependent on functional T cells and did not occur in mice lacking the tyrosine
      kinase p56lck or the tyrosine phosphatase CD45. By contrast, animals lacking the
      T cell-costimulatory molecule CD28 (CD28 -/-) developed autoimmune heart disease,
      although at significantly lower severity than in heterozygous littermates, and
      produced IgG auto-Abs depending on the concentration of the autoantigen
      administered. In addition, the isotypes of IgG auto-Abs specific for cardiac
      myosin differed between CD28 +/- and CD28 -/- mice. Whereas CD28 +/- mice
      predominantly produced Th2-mediated IgG1 auto-Abs, CD28 -/- mice produced
      predominantly IgG2a. These data suggest that CD28 costimulation plays a crucial
      role in induction and maintenance of autoimmune heart disease and that CD28
      expression is required for predominant Th2-IgG1 responses in an autoimmune
      setting.

PMID- 8759766
TI  - Inhibition of superantigen-induced proinflammatory cytokine production and
      inflammatory arthritis in MRL-lpr/lpr mice by a transcriptional inhibitor of TNF
      alpha.
AB  - We have used fas-defective MRL-lpr/lpr mice to study the effects of the
      staphylococcal enterotoxin superantigens on the development of autoimmune,
      inflammatory joint disease in animals that are susceptible to the development of
      rheumatoid arthritis-like disease. We show that systematic administration by a
      single i.p. injection of staphylococcal enterotoxin B (SEB; 10 micrograms/mouse)
      caused a mild, inflammatory arthritis +30 days postchallenge in the knee joints
      of young (< 2-mo-old) MRL-lpr/lpr mice, but not aged-matched MRL +/+ mice. In
      aged (> 8-mo-old) MRL-lpr/lpr mice, but not in aged MRL +/+ mice, SEB caused a
      severe, inflammatory arthritis, as assessed histologically, and systemic
      autoimmune disease, including glomerulonephritis and autoantibody production.
      Furthermore, in aged MRL-lpr/lpr mice, SEB but not heat-denatured SEB caused
      acute weight loss and elevated levels of serum proinflammatory cytokines.
      Compared with highly purified peritoneal macrophages obtained from either aged
      MRL +/+, young MRL-lpr/lpr, or young MRL +/+, peritoneal macrophages obtained
      from aged MRL-lpr/lpr mice constitutively expressed 2- to 10-fold greater levels
      of TNF-alpha, IL-1 beta, IL-6, and IL-10, and produced elevated amounts of these
      cytokines when treated in vitro with SEB. SEB-challenged aged MRL-lpr/lpr mice
      treated with anti-TNF mAb (100 micrograms/mouse; every other day), anti-V beta 8
      TCR mAb (250 micrograms/mouse; every other day), or orally with the novel TNF
      alpha inhibitor MDL 201,449A (9-[(1R, 3R)-trans-cyclopentan-3-ol] adenine; 25
      mg/kg/day) exhibited reduced inflammatory arthritis, autoantibody formation, and
      serum TNF-alpha levels, but not IL-10 levels, after +30 days of treatment. These
      data suggest that SEB is an extremely potent macrophage-activating factor in
      vitro and in vivo, enhancing several aspects of autoimmune disease in MRL-lpr/lpr
      mice, and that anti-TNF therapies may have potential use in inflammatory
      arthritis.

PMID- 8759767
TI  - Biochemical characterization and microsequencing of a 205-kDa synovial protein
      stimulatory for T cells and reactive with rheumatoid factor containing sera.
AB  - Synovial fluid (SF) was found to possess stimulatory capacity for the
      proliferation of T cell clones derived from patients with rheumatoid arthritis
      (RA) when cultured together with IL-2. Using chromatography technique and gel
      electrophoresis, a synovial fluid protein with an apparent m.w. of 205 kDa (p205)
      was isolated that demonstrated a bioactivity analogous to that obtained with
      native synovial fluid. After electroelution, p205 dissociated into 70-kDa
      fragment(s). Upon IEF, it appeared as a single band with an isoelectric point of
      6.5, suggesting a noncovalently bound trimer complex. Amino acid sequences of the
      whole protein and of tryptic peptides were determined by N terminal sequencing.
      The N terminal amino acid sequence of the 70-kDa fragment and of the tryptic
      peptides showed no identity to recently described protein sequences. One peptide
      matched, in 11 amino acid residues, with the human IgG1-4 constant heavy chain
      and rheumatoid factor (RF) binding region. The p205 induced the proliferation of
      peripheral blood T cells and long term T cell cultures that had been raised by
      alternate stimulation with IL-2 and p205. In a similar approach, synovial lining
      cells were shown to release a protein with biochemical characteristics similar to
      the synovial fluid-derived p205. Western blot analysis revealed the binding of RF
      containing sera to p205, which was diminished by absorption with an RF reagent.
      These observations suggest that p205 is expressed by synovial cells and may be a
      target for T and B cells in RA.

PMID- 8759768
TI  - T-T cellular interaction between CD4-CD8- regulatory T cells and T cell clones
      presenting TCR peptide. Its implication for TCR vaccination against experimental
      autoimmune encephalomyelitis.
AB  - Regulatory T cells recognizing TCR determinants presumably play a critical role
      in the control of experimental autoimmune encephalomyelitis, a prototype tissue
      specific autoimmune disease. This study was initiated to determine whether
      regulatory T cells can be induced against a V beta 17a CDR2 peptide (residues 50
      68) in SJL/J mice. Although the TCR peptide showed regulatory effects in vivo,
      the presence of T cells specific for the peptide could not be proven with
      conventional proliferation assays. Unexpectedly, in the presence of myelin basic
      protein-specific T clone cells (Tcc), the sensitized spleen cells vigorously
      proliferated in response to the TCR peptide. The subsequent experiment showed
      that this was due to the outstanding capability of the Tcc as APC for the
      exogenous TCR peptide. Using the Tcc as APC, we were able to establish V beta
      17a50-68-specific T cell lines from in vivo primed spleen cells. The line cells
      were MHC class I restricted and dominated by T cells with a distinct surface
      phenotype (CD4-CD8-V beta 17a+). Presentation of the peptide by the Tcc was
      inhibited by treatment with gelonin that could block a MHC class I presentation
      pathway. The ability of T cells to present the TCR peptide was not related to
      their Ag specificity, but correlated with the expression levels of MHC class I
      molecules and adhesion molecules such as intercellular adhesion molecule-1 and B7
      1 on their surface. The TCR peptide-specific T cells produced a soluble
      mediator(s) that is inhibitory for T cell activation and were protective against
      actively induced experimental autoimmune encephalomyelitis. These results show
      that V beta 17a50-68 vaccination induces regulatory CD4-CD8- T cells that could
      interact with T cells presenting relevant TCR fragments.

PMID- 8759769
TI  - Susceptibility of HIV-1 plasma virus to complement-mediated lysis. Evidence for a
      role in clearance of virus in vivo.
AB  - This study was undertaken to directly assess the susceptibility of HIV-1 plasma
      virus to C-mediated lysis. Plasma from HIV-infected individuals was collected and
      ultracentrifuged over 20% sucrose to isolate virions from plasma components
      including anticoagulants, which inhibit C activity. Treatment with C alone in the
      absence of exogenously added Ab caused lysis of virus from all patients (n = 18)
      (range 14 to 86%). This lysis occurred via the classical C pathway and was not
      due to cross-reactive Abs in the C source. Protein A bound a fraction of isolated
      plasma virus and this binding was blocked by purified human Ig suggesting that
      anti-HIV Abs bound to plasma virus could be responsible for inducing C
      activation. A portion of virus bound to CR2 on cells in the absence of
      exogenously added C indicating that virus activated C in vivo. C levels from six
      of six patients were determined to be sufficient to lead to lysis of virus in
      vivo. Since plasma virus appeared more sensitive to C than primary isolates,
      isolated virus was evaluated for the presence of C control proteins. While
      primary isolate virions contained CD46, CD55, and CD59, only CD59 was detected on
      plasma virus. The results of this study strongly suggest that C is activated by a
      portion of plasma virus in vivo due to the binding of Ab. The resultant
      opsonization plus subsequent lysis may be important routes of clearance and
      destruction of plasma virus in infected persons.

PMID- 8759770
TI  - Pathogenesis of post-thymectomy autoimmune gastritis. Identification of anti-H/K
      adenosine triphosphatase-reactive T cells.
AB  - Autoimmune gastritis spontaneously develops following thymectomy of 3-day-old
      BALB/c mice (d3Tx). These mice develop autoantibodies to the gastric parietal
      cell proton pump, H/K ATPase, and aberrant expression of the H/K ATPase in the
      neonatal thymus prevents the induction of disease post-thymectomy. To
      characterize the effector cells mediating autoimmune gastritis, we isolated H/K
      ATPase-enriched preparations of parietal cell microsomes and further purified the
      enzyme by lectin affinity chromatography. Both preparations induced significant
      proliferative responses of gastric lymph node cells, which were mediated by CD4+,
      MHC class II-restricted T cells. Surprisingly, T cells reactive to the Ag could
      only be demonstrated in lymph nodes in the immediate proximity of the stomach;
      little or no response was seen when mesenteric or peripheral lymph nodes were
      tested. It is likely that the H/K ATPase-reactive T cells are actually the
      effector cells in this disease, as they could only be detected in mice that
      developed gastritis, as indicated by anti-parietal cell Ab, gastric inflammation,
      and the presence of cells capable of transferring disease into nu/nu mice. H/K
      ATPase-specific T cell proliferative responses could first be detected 5 wk post
      thymectomy and were accompanied by high background responses at this time point.
      These latter responses may represent enhanced syngeneic MLRs, which we have
      previously shown to be elevated in d3Tx mice. Characterizations of the H/K ATPase
      reactive and self-reactive T cell populations may reveal the factors that break
      peripheral T cell tolerance and lead to the development of organ-specific
      autoimmune disease.

PMID- 8759771
TI  - Eosinophil recruitment following allergen challenge is associated with the
      release of the chemokine RANTES into asthmatic airways.
AB  - Eosinophil infiltration of the airways in response to allergen exposure is a
      characteristic of bronchial asthma. However, the mechanisms by which these cells
      are recruited are poorly understood. We have investigated the presence of
      eosinophil chemotactic activity (ECA) in bronchoalveolar lavage fluid obtained
      from allergic asthmatics (n = 6) 4 h after endobronchial allergen challenge. ECA
      was purified by sequential heparin affinity chromatography and reverse-phase
      HPLC. A single peak of ECA was detected; SDS-PAGE and Western blot analysis
      showed that the peak contained a protein of 8 kDa and corresponded to the
      chemokine RANTES (regulated upon activation, normal T cell expressed and
      secreted). Consistent with this, the ECA was neutralized by an Ab to RANTES.
      Measurement of RANTES by ELISA in 10x concentrated bronchoalveolar lavage fluid
      showed increased levels of this chemokine at the allergen site (median, 187
      pg/ml; range, 46-263 pg/ml) in comparison with a saline challenge control site
      (median, 32.5 pg/ml; range, 11-94 pg/ml), P < 0.005. Furthermore, there was a
      significant correlation between concentrations of immunoreactive RANTES and the
      number of eosinophils at the allergen challenge site (r = 0.8; p < 0.001), but
      not at the saline site (r = 0.2; p = 0.12). These results suggest that RANTES in
      involved in the recruitment of eosinophils into the asthmatic airways after
      allergen challenge.

PMID- 8759772
TI  - Reversible phosphorylation of the C-terminal domain of RNA polymerase II.

PMID- 8759775
TI  - Neurobiological bases of age-related cognitive decline in the rhesus monkey.
AB  - The rhesus monkey offers a useful model of normal human aging because when
      monkeys are tested on a battery of behavioral tasks that can also be used to
      evaluate cognition in humans, it is found that the monkeys undergo an age-related
      decline in several domains of cognitive function as do humans. In monkeys these
      changes begin at about 20 years of age. To determine what gives rise to this
      cognitive decline, we have examined several parameters in the brains of monkeys.
      Some parameters do not change with age. Examples of this are the numbers of
      neurons in the neocortex and hippocampal formation, and the numbers of synapses
      in the hippocampal formation. Changes in other parameters can be positively
      correlated with chronological age; examples of this are numbers of neuritic
      plaques, a decrease in the numbers of neurons in the striatally projecting pars
      compacta of the substantia nigra, and a decrease in the thickness of layer I in
      primary visual cortex. But the most interesting changes are those that correlate
      either with cognitive decline alone, or with both cognitive decline and
      chronological age. Among these are a breakdown in the integrity of myelin around
      axons, an overall reduction in the volume of white matter in the cerebral
      hemispheres, thinning of layer I in area 46 of prefrontal cortex, and decreases
      in the cell density in cortically projecting brain stem nuclei. To date then, our
      studies suggest that the cognitive declines evident in the rhesus monkey may be a
      consequence of changes in layer I and in the integrity of myelinated axons,
      rather than an age-related loss of cortical neurons or synapses, as has long been
      assumed.

PMID- 8759776
TI  - Continuous quality improvement (CQI) in neuropathology.
AB  - Continuous quality improvement activities are mandated by the Joint Commission on
      Accreditation of Healthcare Organizations and the College of American
      Pathologists. In a recent Needs Assessment Survey of neuropathologists undertaken
      by the College of American Pathologists, in cooperation with the American
      Association of Neuropathologists, neuropathologists indicated the need for
      information regarding continuous quality improvement for neuropathology
      laboratories. This article suggests activities that may be incorporated in a
      continuous quality improvement program, including suggested monitors in surgical
      and autopsy neuropathology, as well as an example of a continuous quality
      improvement plan.

PMID- 8759777
TI  - Cold-injury of the cerebral cortex: immunolocalization of cellular proteins and
      blood-brain barrier permeability studies.
AB  - The occurrence of blood-brain barrier (BBB) permeability alterations and
      neovascularization are well documented in the cerebral cortical cold-injury
      model. This model was used to determine whether the glucose transporter (glutI)
      protein was present in endothelium of cerebral vessels with breakdown of BBB to
      protein and when regenerating endothelial cells become immunoreactive for glutI
      protein. Secondly, the protein products of c-fos and c-jun were localized to
      determine whether these early immediate genes are activated in this model.
      Observations were made over a period of 12 hours to 14 days after the cold
      injury. Blood-brain barrier permeability was assessed using horseradish
      peroxidase (HRP) as a tracer. Since HRP may not be able to enter thrombosed
      vessels within the cold lesion, immunohistochemistry was used to detect
      extravasation of endogenous serum proteins using antisera to rat serum proteins.
      The proteins-glut1, GFAP, c-fos and c-jun-were localized by immunohistochemistry.
      Endothelium of vessels which were permeable to protein, whether in the cold
      injury site or in the perilesional area, all contained glut1 protein; hence, the
      presence of glut1 did not appear to correlate with an intact BBB to protein. An
      interesting point is that in the process of neovascularization, regenerating
      endothelial cells become immunoreactive for glut1 at 5 days and this coincides
      with the presence of tight junctions in these cells. Immunoreactivity for c-fos
      was observed in regenerating endothelium within the lesion site, in astrocytes,
      and to a lesser extent in endothelial cells and neurons in the perilesional area.
      Few astrocytes showed immunoreactivity for c-jun at 4 and 5 days. Possibly, the
      growth factors generated to promote angiogenesis and repair led to activation of
      the c-fos gene with deposition of c-fos protein. The results suggest that during
      nervous system development or endothelial regeneration, the presence of glut1 in
      cerebral endothelium coincides with the presence of an intact BBB to protein and
      protein tracers. However, in pathological states presence of glut1 in cerebral
      endothelium does not appear to correlate with an intact BBB to protein. This
      model lends itself to the study of angiogenesis and repair processes in the
      cerebral cortex in an environment unaffected by ischemia and thus the findings
      may be relevant to traumatic injuries of the human cerebral cortex.

PMID- 8759778
TI  - Characterization of the precursor protein of the non-A beta component of senile
      plaques (NACP) in the human central nervous system.
AB  - A novel and highly conserved presynaptic protein has been independently described
      in rodents (synuclein/SYN-1), songbirds (synelfin), and humans (the precursor
      protein of the non-A beta component of senile plaques, NACP); a fragment of the
      latter has been detected in senile plaques in Alzheimer's disease (AD). We
      characterized the expression of NACP in human AD and non-AD brain. A subcellular
      fractionation study demonstrated that NACP was mainly localized to cytosolic
      fractions of human temporal cortex. NACP was also detectable in various membrane
      and vesicular fractions, suggesting that the protein was associated with membrane
      structures including synaptic vesicles. Pericellular immunostaining of the
      neuropil was observed in neocortical and limbic regions, supporting a synaptic
      localization. Senile plaques in AD brains were not immunoreactive, and confocal
      microscopy suggested a loss of NACP immunoreactivity in cored plaques. No
      difference was found in the amount of protein in AD and control frontal cortex,
      as measured by immunoblotting. PCR analysis showed that the full-length mRNA
      product was the major splice form in both AD and control human brains. Thus,
      despite the association of a hydrophobic fragment of NACP with senile plaques,
      our data suggest that the precursor itself is not a significant component of
      plaques and NACP synthesis is not substantially altered in AD. Nevertheless, the
      protein is an abundant component of synaptic regions prone to degeneration in AD,
      and may have a role in the expression or advancement of the disease.

PMID- 8759780
TI  - 1,25 Dihydroxyvitamin D3 exerts regional effects in the central nervous system
      during experimental allergic encephalomyelitis.
AB  - 1,25-dihydroxyvitamin D3 (1,25-D3) is already known to prevent clinical signs of
      experimental allergic encephalomyelitis when animals are treated during the
      immunization phase. In the present work we have evaluated the ability of 1,25-D3
      to inhibit chronic relapsing experimental allergic encephalomylitis (EAE) of the
      Lewis rat, when administered after the beginning of clinical signs. We observed a
      significant clinical improvement in 1,25-D3-treated rats. This effect was
      accompanied by a profound inhibition of CD4 antigen expression by central nervous
      system (CNS) infiltrating monocytes/macrophages and parenchymal microglia. In
      addition, immunohistochemical analysis performed at the time of the second attack
      evidenced a region-specific distribution of inflammatory cells. In the same way,
      some aspects of the effects exerted by 1,25-D3 appeared to vary depending on the
      region considered, namely spinal cord, brainstem, cerebellum, midbrain or
      anterior brain. Thus, in 1,25-D3-treated rats, we observed an almost complete
      inhibition of CD4 antigen expression in the granule cell layer and the adjacent
      white matter of the cerebellum as well as a marked decrease in the number of OX42
      positive cells (macrophages and activated microglia) in anterior brain sections.
      We conclude that 1,25-D3 can exert immunomodulatory effects inside the CNS during
      an ongoing immune process and may thus represent a promising therapy for multiple
      sclerosis.

PMID- 8759779
TI  - Dystrophin, utrophin and beta-dystroglycan expression in skeletal muscle from
      patients with Becker muscular dystrophy.
AB  - The precise localization and semiquantitative correlation of dystrophin, utrophin
      and beta-dystroglycan expression on the sarcolemma of skeletal muscle cells
      obtained from patients with Becker muscular dystrophy (BMD) was studied using
      three types of double immunofluorescence. Staining intensity was measured using a
      confocal laser microscope. Each of these proteins was identified at the same
      locus on the sarcolemma. The staining intensities of dystrophin and utrophin were
      approximately reciprocal at sarcolemmal sites where dystrophin expression was
      obviously observed. The staining intensity of beta-dystroglycan was strong in
      areas where dystrophin staining was also strong and utrophin expression was weak.
      Quantitative analysis revealed that the staining intensity of beta-dystroglycan
      minus that of dystrophin approximated the staining intensity of utrophin,
      indicating that the sum of dystrophin and utrophin expression corresponds to that
      of beta-dystroglycan. These results suggest that utrophin may compensate for
      dystrophin deficiency found in BMD by binding to beta-dystroglycan.

PMID- 8759781
TI  - Localization and expression of ciliary neurotrophic factor (CNTF) in postmortem
      sciatic nerve from patients with motor neuron disease and diabetic neuropathy.
AB  - Ciliary neurotrophic factor (CNTF) is thought to play an important role in the
      maintenance of the mature motor system. The factor is found most abundantly in
      myelinating Schwann cells in the adult sciatic nerve. Lack of neuronal growth
      factors has been proposed as one possible etiology of amyotrophic lateral
      sclerosis (ALS) and spinal muscular atrophy (SMA). Growth factor replacement
      therapies are currently being evaluated as a treatment for motor neuron disease.
      In this report we determined whether the expression of CNTF in sciatic nerve
      differed in patients with motor neuron disease compared to controls or patients
      with another form of axonopathy. We identified 8 patients (7 with ALS and 1 with
      SMA) with motor neuron disease and 6 patients with diabetic motor neuropathy who
      had autopsy material available. Immunoperoxidase staining showed reduced CNTF
      expression in nerves of patients with motor neuron disease but not in patients
      with diabetic motor neuropathy. Decreased CNTF appears be associated with primary
      motor neuron disease rather than a generalized process of axon loss. This result
      supports suggestions that CNTF deficiency may be an important factor in the
      development of motor neuron disease.

PMID- 8759782
TI  - Reduction of calcineurin enzymatic activity in Alzheimer's disease: correlation
      with neuropathologic changes.
AB  - Neurofibrillary tangles (NFT), neuritic plaques, and dystrophic neurites are the
      classic neuropathologic hallmarks of Alzheimer's disease (AD), all of which
      contain to varying degrees abnormally and/or hyperphosphorylated forms of the
      microtubule-associated protein tau. Protein phosphatase 2B (calcineurin)
      dephosphorylates tau isolated from AD brains to control levels in vitro as well
      as regulates tau phosphorylation and function in vivo. It has been hypothesized
      that the changes in tau phosphorylation observed in AD may be due to increases in
      kinase activity and/or decreases in phosphatase activity. In order to investigate
      the latter possibility, we examined calcineurin enzyme activity using the
      substrate para-nitrophenyl-phosphate (pNPP) in postmortem brain samples from
      individuals with moderate to severe AD (n = 8) and age-matched controls (n = 7).
      The stimulation of calcineurin activity by manganese chloride (1 mM) was reduced
      by 60% (p < 0.01) in whole-cell homogenates prepared from AD temporal cortex
      (Brodmann area 38). On the other hand, in P2 membrane fractions, the stimulation
      of calcineurin activity by manganese chloride as well as nickel chloride (1 mM)
      was reduced by 37% (p < 0.05) and 79% (p < 0.01), respectively. The manganese
      stimulated calcineurin activity in the temporal cortex inversely correlated with
      both the number of NFT (r = -0.60, p < 0.02) and neuritic/core plaques (r = 
      0.63, p < 0.02) in whole-cell homogenates, but only with NFT (r = -0.61, p <
      0.02) in P2 membrane fractions. The nickel-stimulated calcineurin activity did
      not correlate with neuropathology measures in either whole-cell or P2 membrane
      fractions. In striate visual cortex (Brodmann area 17), an area relatively
      unaffected in AD, neither whole-cell nor P2 membrane calcineurin activity were
      significantly altered. To our knowledge, this is the first report of a reduction
      in calcineurin phosphatase activity in AD which correlates with the
      neuropathological features in a region-, subcellular fraction-, and divalent
      cation-specific manner.

PMID- 8759783
TI  - Ultrastructural study of the synapses of central chromatolytic anterior horn
      cells in motor neuron disease.
AB  - This report deals with an ultrastructural investigation of the synapses on the
      somata of central chromatolytic anterior horn neurons of seven patients with
      amyotrophic lateral sclerosis (ALS) and four patients with lower motor neuron
      disease (LMND) who had no upper motor neuron or corticospinal tract involvement.
      Specimens from 24 age-matched individuals who died of non-neurological diseases
      served as controls. We examined a total of 171 anterior horn neurons with central
      chromatolysis (51 from ALS, 42 from LMND and 78 from controls), and 174 normal
      appearing anterior horn neurons as controls. The cross-sectional area, the number
      of synapses, and the length of active zone were significantly reduced in the
      chromatolytic neurons of both patients and controls as compared with normal
      appearing neurons of the controls (p < 0.0001). However, regarding chromatolytic
      neurons, no significant differences were seen in the number of synapses, length
      of each individual synapse, and length of its active zone between patients and
      controls and also in the frequency of presynaptic alterations on the somata.
      There was no overall difference between ALS and LMND patients in any of these
      parameters. Our findings suggest that the flow of electrophysiological
      information from afferent fibers to the somata may be greatly impaired in central
      chromatolytic neurons of both control individuals and patients with motor neuron
      disease (MND), and that the observed synaptic alterations may reflect
      pathological events resulting from anterior horn neuron degeneration. It may
      represent a compensatory mechanism of the synapses for diminished synaptic
      function that synapses were relatively well preserved on the somata of central
      chromatolytic neurons of the MND patients as compared with those of the
      chromatolytic neurons of the controls despite of markedly reduced cross-sectional
      area in the former. It also suggests that the pathomechanism involved in central
      chromatolysis differs between normal individuals and patients with MND.

PMID- 8759784
TI  - Site-specific recombination in gram-positive theta-replicating plasmids.
AB  - This review summarises current information on the site-specific recombinases
      encoded by the plasmids of the Gram-positive bacteria that have low guanine and
      cytosine content in their DNA. It focuses on the peculiar biological features of
      the recombination systems encoded by the theta-replicating plasmids and compares
      them with the site-specific recombinases encoded by transposons or plasmids
      originally isolated from Gram-negative bacteria.

PMID- 8759785
TI  - Occurrence of [copper, zinc]-cofactored superoxide dismutase in Pasteurella
      haemolytica and its serotype distribution.
AB  - Fifty-two ovine strains of Pasteurella haemolytica and P. trehalosi representing
      serotypes 1-16 were examined for the presence of [copper, zinc]superoxide
      dismutase DNA sequences. This was done using a combination of polymerase chain
      reaction with degenerate primers based on the sequence of the [Cu,Zn]superoxide
      dismutase gene (sodC) in related species and Southern hybridization using a
      fragment of sodC from P. haemolytica A2 serotype as a probe. Both detection
      methods identified a fragment of the sodC gene in 9/9 strains of P. haemolytica
      serotype 2 examined and in 5/8 strains of serotype 7. No evidence of this gene
      was found in any other serotype of P. haemolytica or in any P. trehalosi
      serotype. Comparison of DNA sequence showed near identity between sodC from the
      A2 and A7 serotypes of P. haemolytica and substantial similarity (70%) to sodC
      previously sequenced in P. multocida, Haemophilus parainfluenzae and H.
      influenzae. Analysis by gel electrophoresis of the superoxide dismutase activity
      present in cell lysates showed that one or more superoxide dismutase is present
      in all serotypes. However, cyanide-inhibitable activity, corresponding to
      [Cu,Zn]superoxide dismutase, was detected only in those strains of serotypes A2
      and A7 which showed evidence of the sodC gene fragment.

PMID- 8759786
TI  - A rapid screening procedure to identify mini-Tn10 insertion mutants of
      Escherichia coli K-12 with altered adhesion properties.
AB  - A rapid screening procedure was developed for detection of Escherichia coli
      mutants with altered adhesion abilities using polystyrene 96-well microtiter
      plates as attachment surfaces. During this assay, bacterial strains grew and
      adhered simultaneously, and attached cells were measured after crystal violet
      staining. Starting with a total of 7000 W3110::Tn10 insertion mutants of E. coli
      K-12 W3110, 50 adhesion-deficient mutants were isolated which showed less than
      40% attachment, and 22 mutants were found with an attachment of 40-75%. Motility
      assays were performed on these 72 mutants, and 34 displayed altered motility.

PMID- 8759787
TI  - Mechanism of clarithromycin resistance in clinical isolates of Helicobacter
      pylori.
AB  - Seventy-three Helicobacter pylori-positive patients were treated with a
      combination of clarithromycin and ranitidine in order to eradicate the bacterium.
      Eradication was successful in 79.5%. In 15 patients eradication failed, and in 11
      cases this was due to clarithromycin resistance. In one patient the infecting
      strain was resistant at the onset of treatment, while in the remaining 10
      patients resistance developed during therapy. These isolates had also become
      resistant to various other antibiotics. Random amplified polymorphic DNA and
      restriction fragment end-labeling analysis of the isolates showed close genetic
      relatedness between pre- and post-treatment isolates, indicating that resistance
      was the result of selection of variants of the infecting strain rather then
      infection with an exogenous resistant strain. Nucleotide sequence comparisons
      revealed that all resistant isolates had a single base pair mutation in the 23S
      rRNA. Since this single point mutation results in co-resistance to various
      antibiotics at high frequencies, caution should be taken when using
      clarithromycin as a single antibiotic.

PMID- 8759788
TI  - 16S-23S ribosomal RNA spacer regions of Acetobacter europaeus and A. xylinum,
      tRNA genes and antitermination sequences.
AB  - The 16S-23S ribosomal RNA spacer regions of Acetobacter europaeus DSM 6160, A.
      xylinum NCIB 11664 and A. xylinum CL27 were amplified by PCR. Specific PCR
      products were obtained from each strain and their nucleotide sequences
      determined. The spacer region of A. europaeus comprises 768 nucleotides (nt),
      that of A. xylinum 778 nt and that of A. xylinum CL27 759 nt. Genes encoding
      tRNAIle and tRNAAla were identified. Putative antitermination sequences were
      found between the tRNAAla sequence and the 5'-terminus of the 23S rRNA coding
      sequence. The boxA element has the nucleotide sequence TGCTCTTTGATA. Based on
      hybridization data of digested chromosomal DNA with spacer-specific probes, the
      copy number of the rrn operons on the chromosome of Acetobacter strains is
      estimated to be four.

PMID- 8759789
TI  - Immunological characterization of serine-glyoxylate aminotransferase and
      hydroxypyruvate reductase from a methylotrophic bacterium, Hyphomicrobium
      methylovorum GM2.
AB  - Immunological characterization of serine-glyoxylate aminotransferase and
      hydroxypyruvate reductase, key enzymes for the assimilation of one-carbon
      compounds in methylotrophs, was performed using antibodies raised against these
      enzymes purified from Hyphomicrobium methylovorum GM2. Immunodiffusion studies
      indicated that serine-glyoxylate aminotransferase and hydroxypyruvate reductase
      of all seven Hyphomicrobium strains tested were immunochemically similar. In
      immunotitration experiments and Western blot analyses of both enzymes in the
      genera Hyphomicrobium and Methylobacterium, the serine-glyoxylate
      aminotransferase of the genus Methylobacterium exhibited low similarity to that
      of the genus Hyphomicrobium. For hydroxypyruvate reductase, no immunological
      relationship was observed between the genera Hyphomicrobium and Methylobacterium,
      which was in agreement with the differences in primary structure and
      enzymological properties.

PMID- 8759790
TI  - Comparison of the inhibitory action on Saccharomyces cerevisiae of weak-acid
      preservatives, uncouplers, and medium-chain fatty acids.
AB  - This study was initiated to establish whether inhibition of growth of yeasts by
      medium-chain fatty acids resembled that caused by weak-acid preservatives or
      uncouplers. Unlike sorbic acid and 2,4-dinitrophenol, decanoic acid caused rapid
      cell death at its inhibitory concentration. This suggested a mode of action by
      medium-chain fatty acids, distinct from both weak-acid preservatives and
      uncouplers. Sorbic acid and 2,4-dinitrophenol both increased lag and doubling
      times, reduced cell yields and inhibitory concentrations of both were highly pH
      sensitive. The possibility is discussed as to whether weak-acid preservatives and
      uncouplers share common modes of inhibition.

PMID- 8759791
TI  - Attachment of bacteria to model solid surfaces: oligo(ethylene glycol) surfaces
      inhibit bacterial attachment.
AB  - Bacterial cell attachment to the surfaces of self-assembled monolayers formed by
      the adsorption of omega-substituted alkanethiols on transparent gold films has
      been studied under defined bacterial culture and flow conditions. Phase contrast
      microscopy was used to quantify the attachment of two organisms, one of medical
      (Staphylococcus epidermidis) and one of marine (Deleya marina) importance. Self
      assembled monolayers terminated with hexa(ethylene glycol), methyl, carboxylic
      acid and fluorocarbon groups were investigated. Over the range of experimental
      conditions, self-assembled monolayers formed from HS(CH2)11(OCH2CH2)6OH were
      found to be uniformly resistant to bacterial attachment, with a 99.7% reduction
      of attachment for both organisms when compared to the most fouled surface for
      each organism. On other surfaces, S. epidermidis and D. marina were shown to
      exhibit very different attachment responses to the wettability of the substratum.
      While the attachment of S. epidermidis correlated positively with surface
      hydrophilicity, D. marina showed a preference for hydrophobic surfaces. This
      study suggests that surfaces incorporating high densities of oligo(ethylene
      glycol) are good candidates for surfaces that interact minimally with bacteria.

PMID- 8759792
TI  - Characterization of Borrelia sp. isolated from Ixodes tanuki, I. turdus, and I.
      columnae in Japan by restriction fragment length polymorphism of rrf (5S)-rrl
      (23S) intergenic spacer amplicons.
AB  - Borrelia isolated from various sources in Japan, including rare species of ixodid
      ticks, Ixodes tanuki, I. turdus, and I. columnae, were characterized by
      restriction fragment length polymorphism analysis and sequencing analysis of the
      5S-23S rRNA intergenic spacer amplicon. Borrelia sp. isolated from I. tanuki, I.
      turdus and I. columnae generated restriction fragment length polymorphism
      patterns different from those of known B. burgdorferi sensu lato isolates
      previously reported. Furthermore, some B. afzelii and B. garinii isolated in
      Japan showed unique RFLP patterns which were not observed among European B.
      afzelii and B. garinii.

PMID- 8759793
TI  - Rapid distinction between Leptonema and Leptospira by PCR amplification of 16S
      23S ribosomal DNA spacer.
AB  - The PCR amplification of the genomic DNA of Leptonema illini strain 3055 using
      primers directed against conserved regions of the rRNA operon provided evidence
      that the 16S and 23S rRNA genes were linked via an intergenic spacer region. The
      sequencing of the intergenic spacer region indicated that it was 435 nucleotides
      in length and sequence similarity searches revealed that it bore no homology to
      any known sequences including tRNA available in databases. Further investigations
      using Southern blot hybridization revealed that there were two copies of these
      linked genes in the genome. However, similar PCR studies on a representative
      strain from each of the 23 serogroups of Leptospira interrogans, which are
      pathogenic, and eight strains from the 6 serogroups of Leptospira biflexa, which
      are non-pathogenic, revealed that the 16S and 23S rRNA genes were not linked.

PMID- 8759794
TI  - A sequence-specific DNA-binding protein interacts with the xlnC upstream region
      of Streptomyces sp. strain EC3.
AB  - The alignment of the promoter region of several Streptomyces xylanases shows
      three conserved sequences which could be involved in gene regulation. By
      electromobility shift assays these specific sequences, present only in
      Streptomyces xylanolytic strains, were identified as protein-binding sites. The
      sequence required for efficient recognition by the retarding protein appeared to
      be a 4-bp inverted repeat: 5'-CTTT-Nx-AAAG-3'. The DNA-protein affinity was
      influenced by the culture conditions.

PMID- 8759795
TI  - Characterization of the genes encoding a phosphate-regulated two component
      sensory system in the marine cyanobacterium Synechococcus sp. WH7803.
AB  - An oligomer probe was designed to detect the presence of a putative phoB gene in
      the genome of the marine, phycoerythrin-containing cyanobacterium Synechococcus
      sp. WH7803. A 2.2 kb PstI fragment, identified using this probe, was cloned and
      the complete nucleotide sequence determined. The fragment contained two open
      reading frames encoding polypeptides which display all the sequence features
      expected of the response regulator and histidine protein kinase elements of a two
      component sensory system. Northern analysis confirmed that transcription of these
      genes was induced by phosphate limitation. On the basis of the sequence
      similarities and the regulation of their transcription by the availability of
      inorganic phosphate (Pi) these open reading frames were designated as phoB and
      phoR, respectively.

PMID- 8759796
TI  - Cloning of the fliI gene from Rhodobacter sphaeroides WS8 by analysis of a
      transposon mutant with impaired motility.
AB  - A transposon mutant of Rhodobacter sphaeroides WS8 was isolated that showed
      reduced swarming on soft agar plates. Liquid cultures of this mutant (M18) showed
      a low percentage of motile swimming cells in mid-exponential phase and a low
      level of extracellular flagellin protein by Western blotting. M18 was
      complemented by a clone from a library of R. sphaeroides WS8 DNA, and restriction
      mapping of the site of TnphoA insertion in the mutant, coupled with DNA
      sequencing, showed that it had a defect in the fliI gene. To determine if a
      partly functional fliI gene was giving the low-motility phenotype of M18, a drug
      resistance omega cartridge was inserted into the gene to give a complete null
      mutant. This null strain also produced a low percentage of motile cells. Possible
      reasons for this apparent fliI-independent flagellar formation are discussed.

PMID- 8759797
TI  - Expression of the fibrinogen binding mannoprotein and the laminin receptor of
      Candida albicans in vitro and in infected tissues.
AB  - We have previously reported a 37 kDa laminin-binding protein (p37) and a 58 kDa
      fibrinogen-binding mannoprotein (mp58) on the surface of Candida albicans. A few
      yeast cells expressed both functional receptors at the surface while germ tubes
      expressed a functional mp58 fibrinogen but not a functional p37 laminin receptor.
      These receptors were heterogeneously dispersed at the surface as shown by binding
      of rabbit antiserum to mp58 (PAb anti-mp58) and antiserum to the human high
      affinity laminin receptor. In this report we have used a dual fluorescence
      technique to determine if the two receptors colocalize, perhaps as part of a
      receptor complex. Fibrinogen was used as a probe for mp58 and polyclonal
      antiserum generated to the p37 (PAb anti-p37) was used as a probe for the 37 kDa
      laminin-binding protein. Both receptors were heterogeneously distributed, but the
      receptors were not colocalized as the areas of concentration of each receptor
      were different. Immunohistochemical analysis of tissue sections from patients
      with disseminated and superficial candidiasis with PAb anti-p37 and PAb anti-mp58
      revealed that both receptors were also expressed in infected tissues. The
      patterns of morphological expression were similar to the in vitro patterns
      detected by immunofluorescence.

PMID- 8759798
TI  - High frequency gene conversion among benomyl resistant transformants in the
      entomopathogenic fungus Metarhizium anisopliae.
AB  - Three different methods, (i) PEG, (ii) electroporation and (iii) biolistic, were
      employed to transform Metarhizium anisopliae using benomyl resistance as a
      selectable marker. Transformation frequencies and mitotic stability varied for
      each method, from 0.8 to 6.9 transformants micrograms-1 of DNA and 46%,
      respectively, by the PEG method; 1.3 to 1.8 transformants micrograms-1 of DNA and
      67% by electroporation; and 32 to 201 transformants micrograms-1 of DNA and 90%
      by biolistic. We demonstrate by PCR that 60% of the transformants were generated
      by gene conversion.

PMID- 8759799
TI  - Complete development of Cryptosporidium parvum in MDBK cells.
AB  - Sporozoites of Cryptosporidium parvum excysted in vitro from bovine oocysts were
      incubated with monolayers of Madin-Darby bovine kidney cells. The extent of
      parasite colonisation was monitored by light microscopy and immunofluorescence.
      Electron microscopy confirmed the complete development and replication of C.
      parvum within Madin-Darby bovine kidney cells.

PMID- 8759800
TI  - Incidence and treatment of elastic recoil occurring in the 15 minutes following
      successful percutaneous transluminal coronary angioplasty.
AB  - This study was performed (1) to assess the incidence and magnitude of elastic
      recoil occurring within 15 minutes of successful coronary angioplasty, and (2) to
      determine the effect of subsequent additional balloon inflations on coronary
      luminal diameter in patients displaying substantial recoil. The coronary
      angiograms of 50 consecutive patients who underwent a successful percutaneous
      transluminal coronary angioplasty were analyzed using computer-assisted
      quantitative analysis. The patients were divided into 2 groups based on the
      magnitude of early elastic recoil following angioplasty: those with < or = 10%
      (group I, n = 30) and those with > 10% (group II, n = 20) loss of minimal luminal
      diameter as assessed by comparing the angiogram obtained immediately after
      successful angioplasty with that obtained 15 minutes later. The 2 groups were
      similar in clinical, angiographic, and procedural characteristics. Of the 20
      group II subjects, 18 (90%) underwent repeat balloon dilatations, and 2 patients
      (10%) had no further intervention. After additional balloon inflations were
      performed in these 18 patients, 16 (90%) had a final result with < 10% loss of
      minimal luminal diameter 15 minutes later. In conclusion, elastic recoil 15
      minutes after apparently successful percutaneous transluminal coronary
      angioplasty is frequent, occurring in approximately 40% of patients, and is
      attenuated in 90% of subjects with additional balloon inflations. The resultant
      larger lumen diameter may exert a salutary effect on long-term outcome.

PMID- 8759801
TI  - Indications, practice, and procedural outcomes of percutaneous transluminal
      coronary angioplasty in northern New England in the early 1990s. The Northern New
      England Cardiovascular Disease Study Group.
AB  - We conducted a prospective cohort study from October 1, 1989 to December 31, 1993
      of the current indications, practices and procedural outcomes of percutaneous
      transluminal coronary angioplasty (PTCA) in Northern New England to determine how
      it compared with reports from other regions and registries. Thirty-five
      cardiologists contributed data on 12,232 admissions for PTCA performed at all
      hospitals in New Hampshire and Maine, plus 1 in Massachusetts, supporting PTCA.
      Mean patient age was 61.1 years, 67.5% were men, and 38.5% had multivessel
      disease. Unstable (45.6%), stable (22.9%), and postinfarction angina (21.0%) were
      common indications for the procedure. Of all patients, 86.9% had 1-vessel PTCA,
      including 65.7% of those with multivessel disease. Angiographic success was
      90.4%, and 88.1% of patients had > or = 1 lesion successfully dilated and no
      adverse clinical event. The risk of death, nonfatal acute myocardial infarction,
      or coronary artery bypass grafting was 5.7%. The practice and outcomes of PTCA in
      Northern New England were somewhat similar to reports from other regional
      registries but different from a registry of select institutions. We conclude that
      PTCA as performed in Northern New England is safe and effective.

PMID- 8759802
TI  - Association between angina pectoris and ischemic indexes during exercise testing
      and ambulatory monitoring.
AB  - We examined the relation between anginal symptoms and ischemic indexes during
      ischemia on exercise testing and daily activities in 76 patients (59 men and 17
      women, mean age 61.5 years) with documented coronary artery disease and exercise
      induced ischemia. All patients underwent upright bicycle exercise testing and 48
      hour ambulatory electrocardiographic monitoring (AECG). Angina was reported in 28
      patients (37%) during exercise-induced ischemia. A total of 287 ischemic episodes
      were detected from 44 patients (58%) during AECG. There was a mean number of 7.4
      episodes and a mean total duration of 75 min/48 hours. There were no differences
      in the prevalence and the magnitude of ambulatory ischemia between patients with
      and without angina during exercise testing. Among the 44 patients who had
      ischemia during both tests, 50% of patients with angina during exercise testing
      had symptomatic ischemia during AECG compared to 14% in patients with silent
      ischemia during exercise testing (p = 0.01). Ninety-two percent of ischemic
      episodes were preceded by an increase in heart rate (HR) of > 10 beats/min. There
      was a strong positive correlation (r = 0.70, p < 0.01) between HR at onset of 1
      mm ST depression (ischemic threshold) during exercise testing and during AECG. We
      conclude that (1) patients with exercise-induced angina have significantly more
      symptoms during ambulatory ischemia, (2) ischemic threshold during exercise
      testing and daily life are positively correlated, and (3) our findings emphasize
      the role of increased myocardial oxygen demand in the development of ambulatory
      ischemia.

PMID- 8759803
TI  - Trends in coronary thrombolytic therapy for acute myocardial infarction (the
      Minnesota Heart Survey Registry, 1990 to 1993).
AB  - Between 1990 and 1993, patient selection and relative effectiveness of
      thrombolytic agents were issues for clinical trials of thrombolytic therapy,
      particularly the Third International Study of Infarct Survival (ISIS-3) and the
      Second Gruppo Italiano per Lo Studio della Streptochinasi nell'Infarto Miocardico
      trials. The purpose of this report is to document the use of coronary
      thrombolytic therapy in community hospital practice during this period. Patients
      admitted to the coronary care unit of 6 hospitals with suspect acute myocardial
      infarction (AMI) between 1990 and 1993 were prospectively enrolled in the
      Minnesota Heart Survey Registry. Of the 1,225 patients with AMI enrolled, 310 men
      (37%) and 103 women (26%) received thrombolytic therapy (p < 0.001). The age
      adjusted male-to-female odds ratio (95% confidence interval) for receiving
      thrombolysis among patients with < or = 12 hours since symptom onset was 1.33
      (0.94, 1.87). The proportion of those treated receiving tissue plasminogen
      activator declined from 196 (64%) to 102 (34%) between 1990 and 1991 and 1992 and
      1993. Use of streptokinase increased from 48 (16%) to 156 (52%) during the same
      time period. There were no statistically significant gender or lytic agent type
      differences in complications from thrombolytic therapy. Changes in type of agent
      used coincided with the release of results from the ISIS-3 trial.

PMID- 8759804
TI  - Gender and referral for coronary angiography after treadmill thallium testing.
AB  - Considerable controversy exists regarding whether women are less likely than men
      to be referred to coronary angiography after an abnormal noninvasive test. This
      prospective cohort study analyzed consecutive subjects (2,351 men and 1,318
      women) with no prior history of invasive cardiac procedures who were referred for
      treadmill thallium testing at the Cleveland Clinic Foundation. The primary end
      point was performance of coronary angiography within 90 days of treadmill
      thallium testing. A secondary end point was all-cause mortality during 1.8 years
      of follow-up. Women were less likely than men to undergo coronary angiography (6%
      vs 14%, odds ratio [OR] 0.42, 95% confidence interval [Cl] 0.33 to 0.54, p <
      0.001), but were also less likely to have an abnormal thallium scan (8% vs 29%, p
      < 0.001). In logistic regression analyses with adjustment for thallium result and
      age, women were as likely as men to be referred for coronary angiography
      (adjusted OR 1.00, 95% Cl 0.75 to 1.34, p > 0.9). Women were less likely to have
      severe coronary disease on angiography (15% vs 30%, p = 0.006). During 1.8 years
      of follow-up there were 26 deaths (2%) among women and 84 deaths (4%) among men.
      After adjusting for age, thallium abnormalities, and clinical characteristics in
      Cox regression analyses, women had a lower mortality rate than men (relative risk
      0.58, 95% Cl 0.36 to 0.94, p = 0.03). Thus, gender-related differences in
      referral for coronary angiography after treadmill thallium testing can be
      explained by a higher rate of abnormal tests in men. No evidence of a post-test
      gender bias was detected, but a pretest bias affecting referral to nuclear
      testing cannot be excluded. Furthermore, women have a lower prevalence of severe
      coronary disease and a lower adjusted mortality rate.

PMID- 8759805
TI  - Diagnostic value of B-type natriuretic peptide concentrations in patients with
      acute myocardial infarction.
AB  - Although elevations of plasma atrial natriuretic peptide (ANP) concentrations
      have been shown to have prognostic significance in patients after acute
      myocardial infarction (AMI), the relation between plasma levels of B-type
      natriuretic peptide (BNP) and cardiovascular mortality remains unknown. To test
      the prognostic value of plasma ANP and BNP after AMI, plasma concentrations were
      measured a mean of 3 days after infarction in 75 patients. During a median follow
      up of 19.7 months, 14 patients (18.4%) died of cardiovascular causes. On
      univariate analysis, plasma ANP and BNP, Killip class, modified Peel index, left
      ventricular ejection fraction, and presence of left ventricular failure were all
      associated with cardiovascular mortality. In contrast, plasma ANP was the only
      variable that correlated with the development of symptomatic heart failure and
      hospitalization. For the combined end point of cardiovascular mortality,
      symptomatic heart failure, and hospitalization, plasma neurohormones were the
      only variables of predictive value. By stepwise regression analysis, plasma BNP
      was the only significant independent predictor of cardiovascular mortality (p =
      0.001), whereas plasma ANP identified patients at risk of symptomatic heart
      failure and hospitalization (p = 0.002 and 0.019, respectively). This study
      indicates that plasma BNP measured after AMI is a powerful neurohormonal
      predictor of subsequent cardiovascular mortality, whereas plasma ANP correlates
      better with the development of symptomatic heart failure and hospitalization.
      Routine measurement of both of these peptides in the period immediately after an
      AMI may provide a simple means of risk stratification with different information
      gained from each peptide.

PMID- 8759806
TI  - Effects of the intracoronary infusion of cocaine on coronary arterial dimensions
      and blood flow in humans.
AB  - This study was done to assess the influence of large concentrations of cocaine
      (infused into the left coronary artery) on coronary arterial dimensions and blood
      flow in humans. In 20 subjects undergoing cardiac catheterization, incrementally
      increasing doses of (1) saline solution (n = 10, controls) or (2) cocaine
      hydrochloride (n = 10) were infused into the left coronary artery, and the
      effects on heart rate, systemic arterial pressure, coronary sinus blood flow, and
      coronary arterial dimensions were measured. Saline solution induced no change in
      any variable. With the infusion of cocaine, there was an incremental increase in
      its concentration in the systemic (femoral arterial) and coronary (coronary
      sinus) circulations (maximal concentrations, 0.14 +/- 0.06 [mean+/-SD] and 3.50
      +/- 0.70 mg/L, respectively). At the maximal cocaine infusion rate, heart rate
      and diastolic arterial pressure increased slightly, but coronary sinus blood flow
      and the dimensions of nondiseased and diseased coronary arterial segments did not
      change. Thus, intracoronary infusion of cocaine in an amount sufficient to
      achieve a high concentration in the coronary circulation does not induce
      epicardial coronary arterial vasoconstriction or alter blood flow.

PMID- 8759807
TI  - Regional cardiac sympathetic nerve dysfunction and the diagnostic efficacy of
      metaiodobenzylguanidine tomography in stable coronary artery disease.
AB  - The present study endeavors to correlate regional myocardial sympathetic nerve
      dysfunction with reversible and persistent perfusion abnormalities and depressed
      regional wall motion, and to determine the diagnostic efficacy of radio-iodinated
      metaiodobenzylguanidine (MIBG) tomography for detecting coronary artery disease.
      In 28 consecutive patients with stable coronary artery disease and 7 patients
      with atypical chest pain but no coronary stenosis, regional MIBG uptake was
      semiquantitatively evaluated in 13 left ventricular segments early (30 minutes)
      and late (4 hours) after injection. Regional MIBG uptake was reduced in 68 of 90
      segments (76%) showing reversible perfusion abnormality and 72 of 81 segments
      (89%) showing persistent abnormality 4 hours after injection. Although the
      sensitivity and negative predictive values of late MIBG scanning for detecting
      myocardial perfusion abnormalities were relatively high (82% and 85%,
      respectively), the specificity, positive predictive value, and kappa value were
      low (63%, 57%, and 0.41, respectively). Right coronary lesions were detected by
      late MIBG scanning with a high sensitivity (85%) but a low specificity (41%).
      Conversely, the sensitivities for detecting lesions in the other 2 major left
      coronary arteries were low (55%). The overall diagnostic accuracy of late MIBG
      scanning was 66% and the positive and negative predictive values and kappa value
      were low; 60%, 70%, and 0.31, respectively. Similarly, regional sympathetic
      dysfunction was observed in 42 of 49 asynergic segments (86%) on late MIBG scans,
      of which 32 segments were viable and 10 nonviable; but the low specificity (73%)
      and positive predictive value (44%) reduced the kappa value (0.43). Thus,
      regional cardiac sympathetic innervation is impaired in ischemic, asynergic but
      noninfarcted myocardium as well as in myocardium which is infarcted or has a
      persistent perfusion abnormality. The diagnostic efficacy of MIBG tomography to
      detect coronary artery disease, however, is limited probably because of
      nonspecific reductions of MIBG uptake in the inferior and posterolateral regions.

PMID- 8759808
TI  - Right ventricular stiffness measured by a new method without volume estimation in
      coronary artery disease.
AB  - This study was designed to measure the right ventricular (RV) stiffness (delta P/
      delta V) with a new method without estimating the RV volume itself. RV stiffness
      has rarely been measured due to the difficulty in estimating the RV volume.
      Without measuring RV volume itself, stiffness can be determined by measuring its
      volume change (delta V). Tricuspid filling flow volume, which is the diastolic RV
      delta V, is measurable by using Doppler echocardiography. Thus, RV stiffness may
      possibly be obtained from Doppler echocardiography combined with high-fidelity RV
      pressure. Subjects consisted of 8 controls, 8 patients with angina pectoris, 8
      with anterior, 8 with posterior, and 8 with inferior prior myocardial infarction.
      Tricuspid annular dimension was measured by 2-dimensional echocardiography and
      the tricuspid annular area was calculated. Velocity-time integral of the
      tricuspid filling flow during the late diastole was measured by pulsed Doppler
      echocardiography. Then, the late diastolic RV delta V was obtained as the product
      of the tricuspid annular area and the integral. The late diastolic RV pressure
      rise (delta P) was also measured with a micromanometer catheter. The RV elastic
      chamber stiffness constant ([delta P/ delta V]/P) was obtained by dividing simple
      stiffness by the mean RV pressure during late diastole. The RV elastic chamber
      stiffness constant did not significantly differ among controls, patients with
      angina pectoris, and those with anterior and posterior myocardial infarction
      (0.0054 +/- 0.0009 vs 0.0057 +/- 0.0018 vs 0.0064 +/- 0.002 vs 0.0052 +/- 0.0019
      ml-1). However, it was significantly increased in patients with inferior
      myocardial infarction (0.010 +/- 0.004 ml-1, p < 0.01 or 0.05) compared with
      those in the other 4 groups. These results suggest (1) that RV stiffness can be
      measured with a new method without RV volume estimation, and (2) that this new
      method is useful in evaluating RV diastolic pathophysiology in patients with
      coronary artery disease.

PMID- 8759809
TI  - Prevalence and identification of abnormal lipoprotein levels in a biracial
      population aged 23 to 35 years (the CARDIA Study). The Coronary Artery Risk
      Development in Young Adults Study.
AB  - This study examines the prevalence of abnormal low-density lipoprotein (LDL) and
      high-density lipoprotein (HDL) cholesterol levels in young adults to determine
      the ability of National Cholesterol Education Program Adult Treatment Panel (ATP)
      guidelines to identify persons with elevated LDL cholesterol, to compare other
      algorithms with those of the ATP, and to determine the contributions of race,
      gender, and other coronary artery disease risk factors to identifying patients
      with elevated LDL and low HDL cholesterol. The cohort was population-based, aged
      23 to 35 years, and included relatively equal numbers of blacks and whites, and
      men and women. The prevalence of LDL cholesterol > or = 160 mg/dl (> 4.1 mmol/L)
      was 5% in black women, 4% in white women, 10% in black men, and 9% in white men.
      ATP identified most participants with elevated LDL cholesterol (range: 58.8% of
      white men to 70.7% of black women). Lipoprotein panels would have been required
      in 6% to 7% of women and to 15% to 18% of men. Algorithms that used nonlipid risk
      factors required more lipoprotein panels and identified fewer additional
      participants at risk. The prevalence of HDL cholesterol < 35 mg/dl (0.9 mmol/L)
      was 3% in women, 7% in black men, and 13% in white men. Algorithms that used
      nonlipid risk factors before measuring HDL cholesterol would require HDL
      cholesterol measurements in 35% of whites and 56% of blacks, but reduced
      sensitivity for identifying low HDL cholesterol (range: 58% in white men to 93%
      in black women). In young adults, algorithms based on nonlipid risk factors and
      family history have lower sensitivity, and increase rather than decrease the
      number of fasting lipoprotein panels required when compared with ATP levels.

PMID- 8759810
TI  - Chronic rise in defibrillation threshold with a hybrid lead system.
AB  - Nonthoracotomy leads have become standard for implantable cardioverter
      defibrillators (ICD) because of low perioperative morbidity, mortality, and
      expense. Reported increases in defibrillation thresholds (DFTs) with these lead
      systems, however, have raised the possibility of an eventual loss of
      defibrillation efficacy. The mechanism of this increase is unknown. In contrast,
      defibrillation efficacy of traditional epicardial lead systems has been
      demonstrated to remain relatively stable. In the present study, we examined the
      implantation and chronic DFTs in 45 patients with a hybrid system (a high right
      atrial coil and an extrapericardial patch) that combines elements from both the
      thoracotomy and nonthoracotomy approach. The mean threshold increased from 11.7
      +/- 3.0 to 15.8 +/- 10.0 J (p < 0.001) and mean impedance increased from 37.0 +/-
      7.7 to 48.8 +/- 9.0 ohms (p < 0.0001). There was a marked (> or = 10 J) increase
      in DFT in 11 patients (24%) including 4 who required reoperation to obtain an
      adequate safety margin. The increase in DFT was unrelated to any of the analyzed
      variables. We conclude that the presence of an extrapericardial patch does not
      prevent the increase in DFT reported with nonthoracotomy lead systems. This
      increase is unpredictable and occurs in almost 25% of patients.

PMID- 8759811
TI  - Effects of waveform and polarity on defibrillation thresholds in humans using a
      transvenous lead system.
AB  - Minimizing defibrillation thresholds is important to allow for implantation of
      downsized pulse generators with reduced outputs while maintaining an adequate
      defibrillation safety margin. Recent studies have demonstrated a significant
      reduction in monophasic defibrillation thresholds with a transvenous lead when
      the polarity was reversed (proximal coil = cathode). However, conflicting data
      exist concerning the effect of polarity reversal on biphasic defibrillation
      thresholds. The present study was designed to evaluate prospectively the effect
      of waveform shape and polarity on defibrillation thresholds in humans. The group
      studied consisted of 26 patients undergoing cardioverter-defibrillator
      implantation for standard indications. All data were obtained with a transvenous
      lead alone configuration. Defibrillation thresholds were determined using a step
      down protocol with the initial waveform and polarity randomized. Reversing
      polarity significantly decreased the delivered energy at defibrillation threshold
      with monophasic waveforms (14.8 +/- 7.1 vs 20.4 +/- 8.9 J; p < 0.001), but had no
      effect on the overall efficacy of biphasic waveforms (11.1 +/- 5.5 vs 12.2 +/-
      6.5 J). In the subgroup of patients with high biphasic defibrillation thresholds
      (> or = 15 J), reversing polarity decreased the defibrillation threshold from
      18.2 +/- 5.1 to 13.3 +/- 5.8 J (p < 0.001). Similarly, the improvement in
      defibrillation thresholds with reversing polarity of monophasic waveforms was
      confined to the subgroup of patients with higher defibrillation thresholds.
      Therefore, the lack of group effect of polarity on biphasic defibrillation
      thresholds may be simply due to the overall lowering of defibrillation thresholds
      by this waveform.

PMID- 8759812
TI  - Effects of the early administration of zofenopril on onset and progression of
      congestive heart failure in patients with anterior wall acute myocardial
      infarction. The SMILE Study Investigators. Survival of Myocardial Infarction Long
      term Evaluation.
AB  - Chronic congestive heart failure (CHF) is a common disease responsible for a high
      mortality and morbidity whose clinical course can be improved by angiotensin
      converting-enzyme (ACE) inhibition. However, limited data are available on the
      effects of ACE inhibitors on the onset and progression of CHF in patients with
      acute myocardial infarction (AMI). The present study was performed as a substudy
      of the Survival of Myocardial Infarction Long-term Evaluation trial and involved
      1,146 patients with anterior wall AMI not undergoing thrombolysis with the
      exclusion of patients with prior history or clinical signs of CHF on admission.
      Patients were randomly allocated to treatment with zofenopril (7.5 to 30 mg twice
      daily) or placebo for a cumulative period of 6 weeks. The prevalence of CHF,
      either mild to moderate or severe, has been the main objective and has been
      evaluated 6 weeks and 1 year after AMI. The overall prevalence of CHF was not
      reduced by zofenopril after both 6 weeks and 12 months. Conversely the prevalence
      of severe CHF (1.6% vs 2.6%: risk reduction 55.5%; 95% confidence interval 9 to
      63; p = 0.0325) and the combined occurrence of death or severe CHF (4.8% vs 8.2%:
      risk reduction 59%; 95% confidence interval 11 to 71; p = 0.024) were reduced
      after 6 weeks of treatment with zofenopril. Moreover, the percentage of patients
      experiencing a deterioration to severe CHF after 1 year was significantly reduced
      with zofenopril (11.0% vs 24.3%; p = 0.001). In conclusion, the early
      administration of zofenopril to patients with AMI attenuates the progression of
      the clinical symptoms of CHF and its clinical consequences, suggesting that ACE
      inhibitors should be regarded as a suitable strategy for the prevention and
      treatment of CHF in patients with AMI.

PMID- 8759813
TI  - Anthropometric, demographic, and cardiovascular predictors of left ventricular
      mass in young children.
AB  - Left ventricular (LV) mass is a strong independent predictor of cardiovascular
      morbidity and mortality. Few longitudinal studies have examined predictors of LV
      mass in children. This study assessed the contributions of anthropometric,
      demographic, and cardiovascular parameters (at rest and after exposure to
      laboratory stressors) as predictors of LV mass 3.6 years after the initial
      examination in a sample of 68 Caucasian and African-American children 7.9 +/- 0.7
      years old. At the initial examination, all subjects had standard anthropometrics
      measured and hemodynamics assessed at rest and during 3 stressors: postural
      change, forehead cold stimulation, and treadmill exercise. On the follow-up
      examination 3 to 4 years later, echocardiographic evaluations were conducted to
      estimate LV mass and related LV geometry. LV mass and LV internal diameter in
      diastole were adjusted for linear growth (LV mass/height2.7 and LV internal
      dimension during diastole/height0.80, respectively). Hierarchical stepwise
      multiple regression analyses were conducted using parameters significant in
      univariate comparisons (p < 0.05). Initial weight (R2 = 0.38), height (R2 =
      0.42), and cardiac output reactivity to standing and treadmill exercise (final
      model R2 = 0.55) were significant predictors of LV mass, whereas LV
      mass/height2.7 was predicted by initial adiposity (R2 = 0.07) and cardiac output
      and systolic pressure reactivity to postural change (final model R2 = 0.25).
      Follow-up relative wall thickness was significantly predicted by ethnicity
      (African-Americans greater than Caucasians, R2 = 0.15), adiposity (R2 = 0.20),
      and systolic pressure reactivity to postural change (final model R2 = 0.28).
      These findings suggest the potential benefit of weight control in childhood as a
      primary prevention for later onset of cardiovascular disease.

PMID- 8759814
TI  - A cost analysis of coronary stenting without anticoagulation versus stenting with
      anticoagulation using warfarin.
AB  - A case-controlled study was performed comparing hospitalization costs and length
      of hospital stay in a group of patients managed with antiplatelet therapy only,
      versus a group treated with anticoagulation using warfarin after coronary artery
      stenting. The patients managed with antiplatelet therapy alone had significantly
      reduced total hospitalization costs and a significantly reduced average hospital
      stay than patients managed with anticoagulation.

PMID- 8759815
TI  - Effects of enalapril on tissue factor in patients with uncomplicated acute
      myocardial infarction.
AB  - In a randomized, double-blind, placebo-controlled study beginning 4 weeks after
      uncomplicated acute myocardial infarction, it was established that the baseline
      plasma tissue factor antigen level was significantly higher in patients with
      myocardial infarction than in control subjects, and enalapril therapy
      significantly reduced the elevated plasma tissue factor antigen level. This may
      be associated with the reduction in the risk of coronary thrombosis seen with the
      use of angiotensin-converting enzyme inhibitors.

PMID- 8759816
TI  - Dobutamine stress testing in the cardiac catheterization laboratory.
AB  - Dobutamine stress ventriculography is a safe test that appears to separate groups
      of patients with and without significant coronary artery stenoses. In this study,
      all 7 patients with significant coronary artery stenoses who reached a heart rate
      > or = 110 beats/min had a positive stress test, whereas 9 of 10 control patients
      had a negative stress test.

PMID- 8759817
TI  - The Dressler syndrome after pulmonary embolism.
AB  - A study was conducted in 14 patients with pericardial syndrome after pulmonary
      embolism. The role of right ventricular myocardial injury and noncardiogenic
      pulmonary edema in this syndrome is considered and its existence is established.

PMID- 8759818
TI  - Ablation therapy of type I atrial flutter may eradicate paroxysmal atrial
      fibrillation.
AB  - In patients with paroxysms of atrial fibrillation preceded by episodes of atrial
      flutter on Holter monitoring, eradication of the flutter circuit may also abolish
      the episodes of atrial fibrillation. At electrophysiology study, these patients
      are identified by documentation of simultaneous flutter of the right atrium and
      fibrillation of the left atrium.

PMID- 8759819
TI  - Effects of intravenous propranolol on cardiovascular hemodynamics during
      supraventricular tachycardia.
AB  - Hemodynamic variables were evaluated in 10 patients during supraventricular
      tachycardia before and after administration of intravenous propranolol. The drug
      markedly worsened the already compromised hemodynamic pattern of supraventricular
      tachycardia.

PMID- 8759820
TI  - Ambulatory blood pressure monitoring in atrial fibrillation.
AB  - Ambulatory blood pressure monitoring (ABPM) devices are increasingly used in the
      assessment of hypertension, but patients with atrial fibrillation are usually
      excluded because device accuracy in this patient group is unproved. The present
      study investigates the clinical use of the Spacelabs 90207 oscillometric ABPM
      device in outpatients with chronic atrial fibrillation and suggests that such
      devices can be used in clinical practice to assess blood pressure in stable
      outpatients with chronic atrial fibrillation.

PMID- 8759821
TI  - Concomitant factors of decompensation in chronic heart failure.
AB  - The concomitant factors implicated in 328 nonfatal decompensations of 304
      patients with congestive heart failure were: arrhythmias in 24%, infections in
      23%, poor compliance in 15%, angina in 14%, iatrogenic factors in 10%, and other
      causes in 5% of cases. New York Heart Association class and right atrial pressure
      significantly related to the occurrence of decompensation. Poor compliance and
      angina were unpredictable, infection was related to pulmonary wedge pressure,
      iatrogenic factors were predicted by the more advanced functional classes,
      whereas arrhythmias were more frequent in patients with renal failure.

PMID- 8759822
TI  - Natural history and left ventricular response in chronic aortic regurgitation.
AB  - This study was aimed at clarifying the natural history and left ventricular
      response in aortic regurgitation using M-mode echocardiography. We analyzed the
      history and echocardiographic data on 94 patients, who were divided into 4 stages
      according to symptoms. The duration of the asymptomatic period, which represents
      pure volume overload, is long, and the period of minimal symptoms, combined
      volume and pressure overload, is relatively short. Patients with overt heart
      failure due to impaired contractility can survive longer than is usually
      believed, and the factor that predicted the onset of heart failure was a decrease
      in fractional shortening > 3.8 percentage points.

PMID- 8759823
TI  - Angiotensin-converting enzyme and heart chymase gene polymorphisms in
      hypertrophic cardiomyopathy.
AB  - We examined the insertion/deletion polymorphism in the angiotensin-converting
      enzyme gene and identified polymorphisms in the heart chymase gene to test the
      hypothesis that these angiotensin II-producing enzymes are associated with a
      monogenic cardiac disease (50 patients and 50 control subjects) as a model of
      cardiac hypertrophy. We found that the angiotensin-converting enzyme DD genotype
      was present more often in patients than in control subjects and identified a
      possible interaction with 1 of the chymase polymorphisms.

PMID- 8759824
TI  - Evaluation of left atrial appendage stasis in patients with atrial fibrillation
      using transesophageal echocardiography with an intravenous albumin-contrast
      agent.
AB  - To assess stasis in the left atrial appendage in patients with atrial
      fibrillation and to identify patients at increased risk for thromboembolism, we
      performed transesophageal echocardiography with an intravenous albumin contrast
      agent (Albunex) in 25 patients with atrial fibrillation and in 22 patients in
      sinus rhythm. We demonstrated that the absence of opacification in the left
      atrial appendage after Albunex administration implies a high risk of left atrial
      thrombus and cardiogenic thromboembolism.

PMID- 8759825
TI  - Effects of dobutamine on left ventricular diastolic performance are attenuated in
      patients with systemic hypertension.
AB  - We measured Doppler echocardiographic diastolic parameter during infusion of low
      dose dobutamine in 14 untreated hypertensive subjects and in 14 normal controls.
      Low-dose dobutamine accelerated left ventricular relaxation in normal controls
      but not in hypertensive subjects.

PMID- 8759827
TI  - The underused miracle drugs: the statin drugs are to atherosclerosis what
      penicillin was to infectious disease.

PMID- 8759826
TI  - Effect of sotalol on RR interval variability during induced ventricular
      tachycardia.
AB  - The effect of sotalol on the rate and the RR interval variability of induced
      ventricular tachycardia was studied in 26 patients. Sotalol increased the mean
      cycle length and irregularity of RR intervals, which may affect detection of
      ventricular tachycardia by implantable cardioverter-defibrillator devices.

PMID- 8759828
TI  - Left ventricular pacing: a fact, not an artifact.

PMID- 8759829
TI  - Progression in nondilated sites and restenosis: a time-dependent relation.

PMID- 8759830
TI  - Bias in case-control studies of calcium antagonists.

PMID- 8759831
TI  - Long QT syndrome associated with syndactyly in a female.

PMID- 8759832
TI  - Considerations about plasma fibrinogen concentration and the cardiovascular risk:
      combined evidence from the GRIPS and ECAT studies. Goettingen Risk Incidence and
      Prevalence Study. European Concerted Action on Thrombosis and Disabilities.

PMID- 8759833
TI  - Avoiding unnecessary radionuclide exercise stress testing.

PMID- 8759834
TI  - Endothelial function of internal mammary artery grafts.

PMID- 8759835
TI  - Fancy meeting you here! A fresh look at "prokaryotic" protein phosphorylation.
AB  - Bacteria play host to a wide range of protein phosphorylation-dephosphorylation
      systems (Fig. 1). As little as five years ago the known systems were thought to
      be late-emerging and absolutely prokaryote specific. Today we know that most
      protein kinases and protein phosphatases are descended from a set of common, and
      possibly quite ancient, prototypes. Prokaryote- and eukaryote-specific protein
      kinases and protein phosphatases are rare and represent exceptions, not the rule
      as previously thought. Commonality suggests that a dynamic and versatile
      regulatory mechanism was first adapted to the modulation of protein function as
      early if not earlier than more "basic" mechanisms such as allosterism, etc. The
      existence of common molecular themes confirms that the microbial world offers a
      unique, largely untapped library and a powerful set of tools for the
      understanding of a regulatory mechanism which is crucial to all organisms, tools
      whose diversity and experimental malleability will provide new avenues for
      exploring and understanding key modes of cellular regulation.

PMID- 8759836
TI  - A conserved motif in S-layer proteins is involved in peptidoglycan binding in
      Thermus thermophilus.
AB  - There is experimental evidence to suggest that the 100-kDa S-layer protein from
      Thermus thermophilus HB8 binds to the peptidoglycan cell wall. This property
      could be related to the presence of a region (SLH) of homology with other S-layer
      proteins and extracellular enzymes (A. Lupas, H. Engelhardt, J. Peters, U.
      Santarius, S. Volker, and W. Baumeister, J. Bacteriol. 176:1224-1233, 1994). By
      using specific monoclonal antibodies, we show that similar regions are present in
      different members of the Deinococcus-Thermus phylogenetic group. To analyze the
      role that the SLH domain plays in vivo and in vitro in T. thermophilus, we have
      obtained a mutant form (slpA.X) of the S-layer gene (slpA) in which the SLH
      domain was deleted. The slpA.X gene was inserted into the chromosome of the
      thermophile by gene replacement, resulting in a mutant which expressed a major
      membrane protein with the size expected from the construction (90 kDa). This
      protein was identified as the product of slpA.X by its differential reaction with
      monoclonal antibodies. Mutants expressing the SlpA.X protein grow as groups of
      cells, surrounded by a common external envelope of trigonal symmetry that
      contains the SlpA.X protein as a main component, thus showing the inability of
      the SLH-defective protein to attach to the underlying material in vivo. In
      addition, averaged images of SlpA.X-rich fractions showed a regular arrangement,
      identical to that built up by the wild-type (SlpA) protein in the absence of
      peptidoglycan. Finally, we demonstrate by Western blotting (immunoblotting) the
      direct role of the SLH domain in the binding of the S-layer of T. thermophilus
      HB8 to the peptidoglycan layer.

PMID- 8759837
TI  - High-affinity maltose/trehalose transport system in the hyperthermophilic
      archaeon Thermococcus litoralis.
AB  - The hyperthermophilic marine archaeon Thermococcus litoralis exhibits high
      affinity transport activity for maltose and trehalose at 85 degrees C. The K(m)
      for maltose transport was 22 nM, and that for trehalose was 17 nM. In cells that
      had been grown on peptone plus yeast extract, the Vmax for maltose uptake ranged
      from 3.2 to 7.5 nmol/min/mg of protein in different cell cultures. Cells grown in
      peptone without yeast extract did not show significant maltose or trehalose
      uptake. We found that the compound in yeast extract responsible for the induction
      of the maltose and trehalose transport system was trehalose. [14C]maltose uptake
      at 100 nM was not significantly inhibited by glucose, sucrose, or maltotriose at
      a 100 microM concentration but was completely inhibited by trehalose and maltose.
      The inhibitor constant, Ki, of trehalose for inhibiting maltose uptake was 21 nM.
      In contrast, the ability of maltose to inhibit the uptake of trehalose was not
      equally strong. With 20 nM [14C]trehalose as the substrate, a 10-fold excess of
      maltose was necessary to inhibit uptake to 50%. However, full inhibition was
      observed at 2 microM maltose. The detergent-solubilized membranes of trehalose
      induced cells contained a high-affinity binding protein for maltose and
      trehalose, with an M(r) of 48,000, that exhibited the same substrate specificity
      as the transport system found in whole cells. We conclude that maltose and
      trehalose are transported by the same high-affinity membrane-associated system.
      This represents the first report on sugar transport in any hyperthermophilic
      archaeon.

PMID- 8759838
TI  - A sigma E dependent operon subject to catabolite repression during sporulation in
      Bacillus subtilis.
AB  - To identify genes expressed at intermediate stages of Bacillus subtilis
      sporulation, we screened for sigma E-dependent promoters. One promoter that we
      found drives expression of an operon consisting of at least five open reading
      frames (ORFs). The predicted products of the first three ORFs are very homologous
      to enzymes involved in fatty acid metabolism, including acetyl coenzyme A (acetyl
      CoA) acetyltransferase (thiolase), 3-hydroxybutyryl-CoA dehydrogenase, and acyl
      CoA dehydrogenase, respectively. We showed that the fourth ORF encoded a third
      isozyme of citrate synthase in B. subtilis. Genetic evidence and primer extension
      results showed that transcription of this operon is directed by the mother cell
      compartment-specific sigma factor, sigma E, and so the operon was named mmg (for
      mother cell metabolic genes). Furthermore, we found that a sequence (mmgO) with
      homology to a catabolite-responsive element mediates glucose repression of mmg
      promoter activity during sporulation and that this repression was lost in a ccpA
      mutant.

PMID- 8759839
TI  - Identification and functional differentiation of two type I fatty acid synthases
      in Brevibacterium ammoniagenes.
AB  - The fatty acid synthase (FAS) from Brevibacterium ammoniagenes is a homohexameric
      multienzyme complex that catalyzes the synthesis of both saturated and
      unsaturated fatty acids. By immunological screening of a B. ammoniagenes
      expression library, an fas DNA fragment was isolated and subsequently used to
      clone the entire gene together with its flanking sequences. Within 10,525 bp of
      sequenced DNA, the 9,189-bp FAS coding region was identified, corresponding to a
      protein of 3,063 amino acids with a molecular mass of 324,910 Da. This gene
      (fasA) encodes, at its 5' end, the same amino acid sequence as is observed with
      purified B. ammoniagenes FAS. A second reading frame encoding another B.
      ammoniagenes FAS variant (FasB) had been identified previously. Both sequences
      are colinear and exhibit 61 and 47% identity at the DNA and protein levels,
      respectively. By using specific antibodies raised against a unique peptide
      sequence of FasB, this enzyme was shown to represent only 5 to 10% of the
      cellular FAS protein. Insertional inactivation of the FasB coding sequence causes
      no defective phenotype, while fasA disruptants require oleic acid for growth.
      Correspondingly, oleate-dependent B. ammoniagenes cells obtained by ethyl
      methanesulfonate mutagenesis were complemented by transformation with fasA DNA
      but not with fasB DNA. The data indicate that B. ammoniagenes contains two
      related though differently expressed type I FASs. FasA represents the bulk of
      cellular FAS protein and catalyzes the synthesis of both saturated and
      unsaturated fatty acids, while the minor variant, FasB, cannot catalyze the
      synthesis of oleic acid.

PMID- 8759840
TI  - Bacillus subtilis acyl carrier protein is encoded in a cluster of lipid
      biosynthesis genes.
AB  - A cluster of Bacillus subtilis fatty acid synthetic genes was isolated by
      complementation of an Escherichia coli fabD mutant encoding a thermosensitive
      malonyl coenzyme A-acyl carrier protein transacylase. The B. subtilis genomic
      segment contains genes that encode three fatty acid synthetic proteins, malonyl
      coenzyme A-acyl carrier protein transacylase (fabD), 3-ketoacyl-acyl carrier
      protein reductase (fabG), and the N-terminal 14 amino acid residues of acyl
      carrier protein (acpP). Also present is a sequence that encodes a homolog of E.
      coli plsX, a gene that plays a poorly understood role in phospholipid synthesis.
      The B. subtilis plsX gene weakly complemented an E. coli plsX mutant. The order
      of genes in the cluster is plsX fabD fabG acpP, the same order found in E. coli,
      except that in E. coli the fabH gene lies between plsX and fabD. The absence of
      fabH in the B. subtilis cluster is consistent with the different fatty acid
      compositions of the two organisms. The amino acid sequence of B. subtilis acyl
      carrier protein was obtained by sequencing the purified protein, and the sequence
      obtained strongly resembled that of E. coli acyl carrier protein, except that
      most of the protein retained the initiating methionine residue. The B. subtilis
      fab cluster was mapped to the 135 to 145 degrees region of the chromosome.

PMID- 8759841
TI  - Topological analysis of the Rhodobacter capsulatus PucC protein and effects of C
      terminal deletions on light-harvesting complex II.
AB  - A theoretical model for the cytoplasmic membrane topology of the Rhodobacter
      capsulatus PucC protein was derived and tested experimentally with pucC'::pho'A
      gene fusions. The alkaline phosphatase (AP) activities of selected fusions were
      assayed, and the resultant pattern of high and low activity was compared with
      that of the theoretical model. High AP activity correlated well with fusion
      joints located in regions predicted to be periplasmic, and most fusions in
      predicted cytoplasmic loops yield approximately 1/20th as much activity.
      Replacement of pho'A with lac'Z in nine of the fusions confirmed the topology, as
      beta-galactosidase activities were generally reciprocal to the corresponding AP
      activity. On the basis of the theoretical analysis and the information provided
      by the activities of fusions, a model for PucC topology in which there are 12
      membrane-spanning segments and both the N and C termini are located in the
      cytoplasm is proposed. Translationally out-of-frame pucC::phoA fusions were
      expressed in an R. capsulatus delta pucC strain. None of the fusions missing only
      one or two of the proposed C-terminal transmembrane segments restored the wild
      type phenotype, suggesting that the C terminus of PucC is important for function.

PMID- 8759842
TI  - Cloning of a Neisseria meningitidis gene for L-lactate dehydrogenase (L-LDH):
      evidence for a second meningococcal L-LDH with different regulation.
AB  - We report the cloning of lldA, a Neisseria meningitidis gene for L-lactate
      dehydrogenase (L-LDH). Escherichia coli contains a single L-LDH gene (lldD) in
      the lld operon (previously lct). E. coli grown in complex media does not have L
      LDH activity, but the activity is induced by growth in defined medium with L
      lactate as the carbon source. In contrast, meningococci contain at least one L
      LDH in addition to the lldA gene product. These enzymes are active in
      meningococci grown in complex media and are not dependent on growth in L-lactate.
      The predicted amino acid sequence of lldA is homologous to that of E. coli lldD
      and of other prokaryotic and eukaryotic flavin mononucleotide-containing enzymes
      that catalyze the oxidation of L-lactate and other small alpha-hydroxy acids. A
      mutant with a deletion in lldA was found to have reduced L-LDH activity. However,
      this mutant was able to grow on L-lactate, indicating that a second L-LDH must
      exist. Activity of the lldA enzyme was affected by growth conditions, being
      increased by growth on a defined medium with either L-lactate or pyruvate as the
      carbon source. For meningococci grown on a complex medium, activity of the lldA
      enzyme was increased by growth on plates or in well-aerated broth. A second L
      lactate-oxidizing activity was seen in bacteria grown in poorly aerated broth.
      Neisseria gonorrhoeae contains a homolog of lldA. As for meningococci, mutation
      of the gonococcal lldA reduced L-LDH activity but did not affect growth on L
      lactate.

PMID- 8759843
TI  - Isolation and nucleotide sequence of the GDP-mannose:cellobiosyl
      diphosphopolyprenol alpha-mannosyltransferase gene from Acetobacter xylinum.
AB  - A genetic locus from Acetobacter xylinum involved in acetan polysaccharide
      synthesis has been characterized. The chromosomal region was identified by
      screening a genomic library of A. xylinum in a Xanthomonas campestris mutant
      defective in xanthan polysaccharide synthesis. The A. xylinum cosmid clone can
      functionally complement a xanthan-negative mutant. The polymer produced by the
      recombinant strain was found to be indistinguishable from xanthan. Insertion
      mutagenesis and subcloning of the cosmid clone combined with complementation
      studies allowed the identification of a 2.3-kb fragment of A. xylinum chromosomal
      DNA. The nucleotide sequence of this fragment was analyzed and found to contain
      an open reading frame (aceA) of 1,182 bp encoding a protein of 43.2 kDa. Results
      from biochemical and genetic analyses strongly suggest that the aceA gene encodes
      the GDP-mannose:cellobiosyl-diphosphopolyprenol alpha-mannosyltransferase enzyme,
      which is responsible for the transfer of an alpha-mannosyl residue from GDP-Man
      to cellobiosyl-diphosphopolyprenol. A search for similarities with other known
      mannosyltransferases revealed that all bacterial alpha-mannosyltransferases have
      a short COOH-terminal amino acid sequence in common.

PMID- 8759844
TI  - Metabolic activities of metronidazole-sensitive and -resistant strains of
      Helicobacter pylori: repression of pyruvate oxidoreductase and expression of
      isocitrate lyase activity correlate with resistance.
AB  - In this study, we compared metronidazole (Mtz)-sensitive and -resistant strains
      of Helicobacter pylori for metabolic differences that might correlate with drug
      resistance. Included in this study was an isogenic Mtz(r) strain, HP1107, that
      was constructed by transforming genomic DNA from Mtz(r) strain HP439 into Mtz(s)
      strain HP500. Enzyme activities were also measured for Mtz(r) strains grown in
      the presence or absence of 18 micrograms of metronidazole per ml (ca. one-half of
      the MIC). These studies confirmed the presence of the Embden-Meyerhof-Parnas,
      Entner-Doudoroff, and pentose pathways. H. pylori strains expressed enzymatic
      activities indicative of a complete and active Krebs cycle. All strains expressed
      pyruvate oxidoreductase (POR) and alpha-ketoglutarate oxidoreductase (KOR) as
      measured with the redox-active dye benzyl viologen (30 to 96 nmol/min/mg of
      protein for POR and 30 nmol/min/mg of protein for KOR). When grown in the
      presence of Mtz at > or = 3.5 micrograms/ml, Mtz(r) strains expressed no
      detectable POR or KOR activity. The apparent repression of POR and KOR activities
      by Mtz affected bacterial growth as manifest by extended lag periods and growth
      yield reductions of > 30%. A dose-dependent relationship was demonstrated between
      the metronidazole concentration in the growth medium and the specific activity of
      POR measured in bacterial cell extracts. The observed repression was not due to
      inactivation of POR by Mtz. In addition to repression of POR and KOR activities,
      growth in the presence of Mtz also led to decreases in the activities of various
      Krebs cycle enzymes, including aconitase, isocitrate dehydrogenase and succinate
      dehydrogenase. All of the Mtz(r) strains examined expressed isocitrate lyase and
      malate synthase activities indicative of the glyoxylate bypass. No isocitrate
      lyase activity was detected in Mtz(s) strain HP500. Isocitrate lyase activity was
      expressed by HP500 following transformation to Mtz resistance (Mtz(r) strain
      HP1107) with DNA from an Mtz(r) strain. The results of this study suggest that
      Mtz resistance may be a recessive trait, possibly involving inactivation of a
      regulatory gene, that results in constitutive expression of isocitrate lyase.
      Repression of POR and KOR activities in response to low levels of Mtz may be a
      general response of H. pylori strains to Mtz, but only resistant strains manage
      to survive via activation of compensatory metabolic pathways.

PMID- 8759845
TI  - Modulation of NifA activity by PII in Azospirillum brasilense: evidence for a
      regulatory role of the NifA N-terminal domain.
AB  - Azospirillum brasilense NifA, which is synthesized under all physiological
      conditions, exists in an active or inactive from depending on the availability of
      ammonia. The activity also depends on the presence of PII, as NifA is inactive in
      a glnB mutant. To investigate further the mechanism that regulates NifA activity,
      several deletions of the nifA coding sequence covering the amino-terminal domain
      of NifA were constructed. The ability of these truncated NifA proteins to
      activate the nifH promoter in the absence or presence of ammonia was assayed in
      A. brasilense wild-type and mutant strains. Our results suggest that the N
      terminal domain is not essential for NifA activity. This domain plays an
      inhibitory role which prevents NifA activity in the presence of ammonia. The
      truncated proteins were also able to restore nif gene expression to a glnB
      mutant, suggesting that PII is required to activate NifA by preventing the
      inhibitory effect of its N-terminal domain under conditions of nitrogen fixation.
      Low levels of nitrogenase activity in the presence of ammonia were also observed
      when the truncated gene was introduced into a strain devoid of the ADP
      ribosylation control of nitrogenase. We propose a model for the regulation of
      NifA activity in A. brasilense.

PMID- 8759846
TI  - The heat shock protein ClpB mediates the development of thermotolerance in the
      cyanobacterium Synechococcus sp. strain PCC 7942.
AB  - The heat shock protein CIpB (HSP100) is a member of the diverse group of Clp
      polypeptides that function as molecular chaperones and/or regulators of energy
      dependent proteolysis. A single-copy gene coding for a ClpB homolog was cloned
      and sequenced from the unicellular cyanobacterium Synechococcus sp. strain PCC
      7942. The predicted polypeptide sequence was most similar to sequences of
      cytosolic ClpB from bacteria and higher plants (i.e., 70 to 75%). Inactivation of
      clpB in Synechococcus sp. strain PCC 7942 resulted in no significant differences
      from the wild-type phenotype under optimal growth conditions. In the wild type,
      two forms of ClpB were induced during temperature shifts from 37 to 47.5 or 50
      degrees C, one of 92 kDa, which matched the predicted size, and another smaller
      protein of 78 kDa. Both proteins were absent in the delta clpB strain. The level
      of induction of the two ClpB forms in the wild type increased with increasingly
      higher temperatures, while the level of the constitutive ClpC protein remained
      unchanged. In the delta clpB strain, however, the ClpC content almost doubled
      during the heating period, presumably to compensate for the loss of ClpB
      activity. Photosynthetic measurements at 47.5 and 50 degrees C showed that the
      null mutant was no more susceptible to thermal inactivation than the wild type.
      Using photosynthesis as a metabolic indicator, an assay was developed for
      Synechococcus spp. to determine the importance of ClpB for acquired
      thermotolerance. Complete inactivation of photosynthetic oxygen evolution
      occurred in both the wild type and the delta clpB strain when they were shifted
      from 37 directly to 55 degrees C for 10 min. By preexposing the cells at 50
      degrees C for 1.5 h, however, a significant level of photosynthesis was retained
      in the wild type but not in the mutant after the treatment at 55 degrees C for 10
      min. Cell survival determinations confirmed that the loss of ClpB synthesis
      caused a fivefold reduction in the ability of Synechococcus cells to develop
      thermotolerance. These results clearly show that induction of ClpB at high
      temperatures is vital for sustained thermotolerance in Synechococcus spp., the
      first such example for either a photosynthetic or a prokaryotic organism.

PMID- 8759847
TI  - A study of mycobacterial transcriptional apparatus: identification of novel
      features in promoter elements.
AB  - Our earlier studies on transcriptional signals of mycobacteria had revealed that
      (i) strong promoters occur less frequently in the slowly growing pathogen
      Mycobacterium tuberculosis H37Rv than in the fast-growing saprophyte M. smegmatis
      and (ii) mycobacterial promoters function poorly in Escherichia coli. We now
      present evidence that RNA polymerases of M. smegmatis, M. tuberculosis, and M.
      bovis BCG recognize promoter elements with comparable efficiencies. Analysis of
      these randomly isolated mycobacterial promoters by DNA sequencing, primer
      extension, and deletion experiments revealed that their -10 regions are highly
      similar to those of E. coli promoters, in contrast to their -35 regions, which
      can tolerate a greater variety of sequences, owing presumably to the presence of
      multiple sigma factors with different or overlapping specificities for -35
      regions, as reported earlier for the Streptomyces promoters. A comparison of the 
      10 and -35 binding domains of MysA, HrdB, and RpoD (the principal sigma factors
      of M. smegmatis, Streptomyces aureofaciens, and E. coli, respectively) showed
      that all three sigma factors have nearly identical -10 binding domains. However,
      the -35 binding domains of the principal mycobacterial and streptomycete sigma
      factors, although nearly identical to each other, are vastly different from the
      corresponding region of the sigma factor of E. coli. Thus, the transcriptional
      signals of mycobacteria have features in common with Streptomyces promoters but
      differ from those of E. coli because of major differences in the -35 regions of
      the promoters and the corresponding binding domain in the sigma factor.

PMID- 8759848
TI  - Cloning and characterization of nanB, a second Streptococcus pneumoniae
      neuraminidase gene, and purification of the NanB enzyme from recombinant
      Escherichia coli.
AB  - Streptococcus pneumoniae is believed to produce more than one form of
      neuraminidase, but there has been uncertainty as to whether this is due to
      posttranslational modification of a single gene product or the existence of more
      than one neuraminidase-encoding gene. Only one stable pneumococcal neuraminidase
      gene (designated nanA) has been described. In the present study, we isolated and
      characterized a second neuraminidase gene (designated nanB), which is located
      close to nanA on the pneumococcal chromosome (approximately 4.5kb downstream).
      nanB was located on an operon separate from that of nanA, which includes at least
      five other open reading frames. NanB has a predicted size of 74.5 kDa after
      cleavage of a 29-amino-acid signal peptide. There was negligible amino acid
      homology between NanA and NanB, but NanB did exhibit limited homology with the
      sialidase of Clostridium septicum. NanB was purified from recombinant Escherichia
      coli and found to have a pH optimum of 4.5, compared with 6.5 to 7.0 for NanA.
      Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis suggested that
      NanB has a molecular size of approximately 65 kDa. The discrepancy between this
      estimate and the size predicted from the nucleotide sequence is most likely a
      consequence of C-terminal processing or anomalous electrophoretic behavior.

PMID- 8759849
TI  - Effects of mecA and mecB (clpC) mutations on expression of sigD, which encodes an
      alternative sigma factor, and autolysin operons and on flagellin synthesis in
      Bacillus subtilis.
AB  - The expression of the major vegetative phase-specific autolysin genes (cwlB
      [lytC] and cwlG [lytD]) was greatly reduced by mecA and mecB null mutations. In
      contrast to the negative effects on late competence genes (such as comG) and
      levansucrase gene (sacB) expression, this positive effect of mec genes on
      autolysin gene expression was not mediated through the ComK protein but
      apparently through the level of the SigD protein. The pleiotropic effects of the
      mec mutations, i.e., the reduction of sigD expression and the overexpression of
      the ComK protein, seem not to be interwoven since the SigD- and ComK-dependent
      functions are clearly separable in the mec mutants. We also show that the
      synthesis of the flagellin protein, which is encoded by the SigD-dependent hag
      gene, was similarly affected by the mec mutations. Complementation analysis with
      a SigD-overproducing plasmid, pHYSigD, in mec mutants revealed the reversion of
      almost all of the SigD-dependent phenotypes except motility. This finding
      suggested that Mec proteins act on motility genes at two levels, one of which is
      apparently SigD independent. Finally, we discuss the transcriptional regulation
      of the sigD gene by multiple regulators, i.e., MecA, MecB, SinR (FlaD), and DegS
      DegU, and its implications for cells in a global context.

PMID- 8759850
TI  - Replication of a plasmid lacking the normal site for initiation of one strand.
AB  - The origin of replication of the plasmid R1162 contains an initiation site for
      the synthesis of each DNA strand. When one of these sites (oriL) is deleted,
      synthesis on the corresponding strand is no longer initiated efficiently in vitro
      by the R1162-encoded replication proteins, and the plasmid is no longer stably
      maintained in the cell. However, in vivo the two strands of the plasmid duplex
      molecule are active at a similar level as templates for DNA synthesis, and newly
      synthesized copies of each strand are incorporated into daughter molecules at a
      similar rate. No secondary, strong initiation sites on the delta oriL strand were
      detected in the region of the origin. The delta oriL plasmid induces the SOS
      response, and this is important for plasmid maintenance even in a recombination
      proficient strain. Our results indicate that an SOS-induced host system can
      maintain an R1162 derivative lacking one of its initiation sites.

PMID- 8759851
TI  - Identification and characterization of iron-regulated Bordetella pertussis
      alcaligin siderophore biosynthesis genes.
AB  - Bordetella bronchiseptica mutants BRM1, BRM6, and BRM9 fail to produce the native
      dihydroxamate siderophore alcaligin. A 4.5-kb BamHI-Smal Bordetella pertussis
      genomic DNA fragment carried multiple genes required to restore alcaligin
      production to these siderophore-deficient mutants. Phenotypic complementation
      analysis using subclones of the 4.5-kb genomic region demonstrated that the
      closely linked BRM1 and BRM9 mutations were genetically separable from the BRM6
      mutation, and both insertions exerted strong polar effects on expression of the
      downstream gene defined by the BRM6 mutation, suggesting a polycistronic
      transcriptional organization of these alcaligin biosynthesis genes. Subcloning
      and complementation experiments localized the putative Bordetella promoter to a
      0.7-kb BamHI-SphI subregion of the cloned genomic DNA fragment. Nucleotide
      sequencing, phenotypic analysis of mutants, and protein expression by the 4.5-kb
      DNA fragment in Escherichia coli suggested the presence of three alcaligin system
      genes, namely, alcA, alcB, and alcC. The deduced protein products of alcA, alcB,
      and alcC have significant primary amino acid sequence similarities with known
      microbial siderophore biosynthesis enzymes. Primer extension analysis mapped the
      transcriptional start site of the putative alcaligin biosynthesis operon
      containing alcABC to a promoter region overlapping a proposed Fur repressor
      binding site and demonstrated iron regulation at the transcriptional level.

PMID- 8759853
TI  - Atrazine chlorohydrolase from Pseudomonas sp. strain ADP: gene sequence, enzyme
      purification, and protein characterization.
AB  - Pseudomonas sp. strain ADP metabolizes atrazine to carbon dioxide and ammonia via
      the intermediate hydroxyatrazine. The genetic potential to produce
      hydroxyatrazine was previously attributed to a 1.9-kb AvaI DNA fragment from
      strain ADP (M. L. de Souza, L. P. Wackett, K. L. Boundy-Mills, R. T. Mandelbaum,
      and M. J. Sadowsky, Appl. Environ. Microbiol. 61:3373-3378, 1995). In this study,
      sequence analysis of the 1.9-kb AvaI fragment indicated that a single open
      reading frame, atzA, encoded an activity transforming atrazine to
      hydroxyatrazine. The open reading frame for the chlorohydrolase was determined by
      sequencing to be 1,419 nucleotides and encodes a 473-amino-acid protein with a
      predicted subunit molecular weight of 52,421. The deduced amino acid sequence
      matched the first 10 amino acids determined by protein microsequencing. The
      protein AtzA was purified to homogeneity by ammonium sulfate precipitation and
      anion-exchange chromatography. The subunit and holoenzyme molecular weights were
      60,000 and 245,000 as determined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and gel filtration chromatography, respectively. The purified
      enzyme in H2(18)O yielded [18O]hydroxyatrazine, indicating that AtzA is a
      chlorohydrolase and not an oxygenase. The most related protein sequence in
      GenBank was that of TrzA, 41% identity, from Rhodococcus corallinus NRRL B
      15444R. TrzA catalyzes the deamination of melamine and the dechlorination of
      deethylatrazine and desisopropylatrazine but is not active with atrazine. AtzA
      catalyzes the dechlorination of atrazine, simazine, and desethylatrazine but is
      not active with melamine, terbutylazine, or desethyldesisopropylatrazine. Our
      results indicate that AtzA is a novel atrazine-dechlorinating enzyme with fairly
      restricted substrate specificity and contributes to the microbial hydrolysis of
      atrazine to hydroxyatrazine in soils and groundwater.

PMID- 8759852
TI  - Organization of the Escherichia coli K-12 gene cluster responsible for production
      of the extracellular polysaccharide colanic acid.
AB  - Colanic acid (CA) is an extracellular polysaccharide produced by most Escherichia
      coli strains as well as by other species of the family Enterobacteriaceae. We
      have determined the sequence of a 23-kb segment of the E. coli K-12 chromosome
      which includes the cluster of genes necessary for production of CA. The CA
      cluster comprises 19 genes. Two other sequenced genes (orf1.3 and galF), which
      are situated between the CA cluster and the O-antigen cluster, were shown to be
      unnecessary for CA production. The CA cluster includes genes for synthesis of GDP
      L-fucose, one of the precursors of CA, and the gene for one of the enzymes in
      this pathway (GDP-D-mannose 4,6-dehydratase) was identified by biochemical assay.
      Six of the inferred proteins show sequence similarity to glycosyl transferases,
      and two others have sequence similarity to acetyl transferases. Another gene
      (wzx) is predicted to encode a protein with multiple transmembrane segments and
      may function in export of the CA repeat unit from the cytoplasm into the
      periplasm in a process analogous to O-unit export. The first three genes of the
      cluster are predicted to encode an outer membrane lipoprotein, a phosphatase, and
      an inner membrane protein with an ATP-binding domain. Since homologs of these
      genes are found in other extracellular polysaccharide gene clusters, they may
      have a common function, such as export of polysaccharide from the cell.

PMID- 8759854
TI  - Global analysis of the carbon starvation response of a marine Vibrio species with
      disruptions in genes homologous to relA and spoT.
AB  - The stringent control response, which involves a rapid accumulation of ppGpp, is
      triggered if the marine Vibrio sp. strain S14 is subjected to carbon and energy
      starvation. By means of high-resolution two-dimensional gel electrophoresis
      analysis, we addressed the role of the major ppGpp-synthesizing enzyme (RelA) in
      the regulation of the carbon starvation response of Vibrio sp. strain S14. The
      finding that a large number of the carbon starvation-induced proteins were
      underexpressed in the Vibrio sp. S14 relA mutant strain after the onset of
      glucose starvation suggests that a rapid accumulation of ppGpp is required for
      induction of many of the carbon starvation-induced proteins. However, it was also
      found that a majority of the carbon starvation-induced proteins were
      significantly less induced if the stringent control response was provoked by
      amino acid starvation. We therefore also addressed the notion that a carbon
      starvation-specific signal transduction pathway, complementary to the stringent
      control, may exist in Vibrio sp. strain S14. It was found that a majority of the
      proteins that were underexpressed in the relA mutant strain were also
      underexpressed in the Vibrio sp. S14 spoT mutant strain (csrS1). Interestingly, a
      large proportion of these underexpressed proteins were found to belong to a group
      of proteins that are not, or significantly less, induced by starvation conditions
      that do not promote starvation survival. On the basis of these observations and
      the finding that the csrS1 strain survives poorly but accumulates ppGpp in a
      fashion similar to the wild type during carbon and energy source starvation, the
      gene product of the csrS gene is suggested to be responsible for the mediation of
      a signal which is complementary to ppGpp and essential for the successful
      development of the starvation- and stress-resistant cell. This conclusion was
      also supported by experiments in which changes in phenotypic characteristics
      known to be induced during carbon starvation were studied. The starvation
      induction of the high-affinity glucose uptake system was found to be dependent on
      the csrS gene but not relA, and the synthesis of carbon starvation-specific
      periplasmic space proteins was dependent, at different times of starvation, on
      both the relA and the csrS gene products.

PMID- 8759855
TI  - Porin activity of the native and recombinant outer membrane protein Oms28 of
      Borrelia burgdorferi.
AB  - The outer membrane-spanning (Oms) proteins of Borrelia burgdorferi have been
      visualized by freeze-fracture analysis but, until recently, not further
      characterized. We developed a method for the isolation of B. burgdorferi outer
      membrane vesicles and described porin activities with single-channel conductances
      of 0.6 and 12.6 nS in 1 M KCI. By using both nondenaturing isoelectric focusing
      gel electrophoresis and fast-performance liquid chromatography separation after
      detergent solubilization, we found that the 0.6-nS porin activity resided in a 28
      kDa protein, designated Oms28. The oms28 gene was cloned, and its nucleotide
      sequence was determined. The deduced amino acid sequence of Oms28 predicted a 257
      amino-acid precursor protein with a putative 24-amino-acid leader peptidase I
      signal sequence. Processed Oms28 yielded a mature protein with a predicted
      molecular mass of 25,363 Da. When overproduced in Escherichia coli, the Oms28
      porin fractionated in part to the outer membrane. Sodium dodecyl sulfate
      polyacrylamide gel-purified recombinant Oms28 from E. coli retained functional
      activity as demonstrated by an average single-channel conductance of 1.1 nS in
      the planar lipid bilayer assay. These findings confirmed that Oms28 is a B.
      burgdorferi porin, the first to be described. As such, it is potential relevance
      to the pathogenesis of Lyme borreliosis and to the physiology of the spirochete.

PMID- 8759856
TI  - The role of the 5'-end untranslated region of the mRNA for CspA, the major cold
      shock protein of Escherichia coli, in cold-shock adaptation.
AB  - During cellular adaptation to low temperature, Escherichia coli transiently
      synthesizes the major cold-shock protein CspA. It was found that adaptation to
      cold shock is blocked when the 143-base sequence of the 5' untranslated region
      (5' UTR) of the cspA mRNA is overproduced. The overproduction of this UTR at 15
      degrees C caused the synthesis of not only CspA but also other cold-shock
      proteins such as CspB and CsdA to be no longer transient but rather prolonged. In
      addition, inhibition of both the synthesis of cellular proteins other than cold
      shock proteins and cell growth was observed. Interestingly, when CspA was also
      overproduced together with the 5' UTR, normal cold-shock adaptive response was
      resumed without a prolonged lag period of cell growth. This indicates that the 5'
      UTR of the cspA mRNA and its gene product CspA play a critical role in the
      regulation of the expression of cold-shock genes and cold-shock adaptation. An 11
      base common sequence (cold box) was found in the 5' UTRs of cspA, cspB, and csdA
      mRNAs. Indeed, the 25-base sequence within the 5' UTR of the cspA mRNA containing
      the cold-box sequence was able to prolong CspA production at 15 degrees C. We
      propose that a putative repressor binds to the cold-box sequence of the cold
      shock mRNAs during the adaptive process and this binding in turn blocks the
      transcription of the cold-shock genes or destabilizes their mRNAs. CspA appears
      to promote either directly or indirectly the repressor function.

PMID- 8759857
TI  - 2,4-Dinitrotoluene dioxygenase from Burkholderia sp. strain DNT: similarity to
      naphthalene dioxygenase.
AB  - 2,4-Dinitrotoluene (DNT) dioxygenase from Burkholderia sp. strain DNT catalyzes
      the initial oxidation of DNT to form 4-methyl-5-nitrocatechol (MNC) and nitrite.
      The displacement of the aromatic nitro group by dioxygenases has only recently
      been described, and nothing is known about the evolutionary origin of the enzyme
      systems that catalyze these reactions. We have shown previously that the gene
      encoding DNT dioxygenase is localized on a degradative plasmid within a 6.8-kb
      NsiI DNA fragment (W.-C. Suen and J. C. Spain, J. Bacteriol. 175:1831-1837,
      1993). We describe here the sequence analysis and the substrate range of the
      enzyme system encoded by this fragment. Five open reading frames were identified,
      four of which have a high degree of similarity (59 to 78% identity) to the
      components of naphthalene dioxygenase (NDO) from Pseudomonas strains. The
      conserved amino acid residues within NDO that are involved in cofactor binding
      were also identified in the gene encoding DNT dioxygenase. An Escherichia coli
      clone that expressed DNT dioxygenase converted DNT to MNC and also converted
      naphthalene to (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene. In contrast, the
      E. coli clone that expressed NDO did not oxidize DNT. Furthermore, the enzyme
      systems exhibit similar broad substrate specificities and can oxidize such
      compounds as indole, indan, indene, phenetole, and acenaphthene. These results
      suggest that DNT dioxygenase and the NDO enzyme system share a common ancestor.

PMID- 8759858
TI  - ADP-ribosylation of proteins in Bacillus subtilis and its possible importance in
      sporulation.
AB  - Endogenous ADP-ribosylation was detected in Bacillus subtilis, as determined in
      vitro with crude cellular extracts. The ADP-ribosylated protein profile changed
      during growth in sporulation medium, displaying a temporary appearance of two ADP
      ribosylated proteins (36 and 58 kDa) shortly after the end of exponential growth.
      Mutants resistant to 3-methoxybenzamide, a known inhibitor of ADP
      ribosyltransferase, were obtained, and a significant proportion (15%) were found
      to be defective in both sporulation and antibiotic production. These mutants
      failed to ADP-ribosylate the 36- and 58-kDa proteins. The parent strain also lost
      the ability to ADP-ribosylate these proteins when grown in the presence of 3
      methoxybenzamide at a concentration at which sporulation but not cell growth was
      severely inhibited. Results from genetic transformations showed that the mutation
      conferring resistance to 3-methoxybenzamide, named brgA, was cotransformed with
      the altered phenotypes, i.e., defects in ADP-ribosylation and sporulation. spoOA
      and spoOF mutants displayed an ADP-ribosylation profile similar to that of the
      parent strain, but a spoOH mutant failed to ADP-ribosylate any proteins,
      including the 36- and 58-kDa proteins. The significance of protein ADP
      ribosylation in sporulation was further indicated by the observation that ADP
      ribosylation of the 36-kDa protein could be induced by treatment with decoyinine,
      an inhibitor of GMP-synthetase, and by amino acid limitation, both of which
      resulted in an immediate decrease in GTP pool size eventually leading to massive
      sporulation. We propose that a new sporulation gene, which presumably controls
      sporulation via ADP-ribosylation of certain functional proteins, exists.

PMID- 8759859
TI  - Fermentative arginine degradation in Halobacterium salinarium (formerly
      Halobacterium halobium): genes, gene products, and transcripts of the arcRACB
      gene cluster.
AB  - Fermentative growth via the arginine deiminase pathway is mediated by the enzymes
      arginine deiminase, carbamate kinase, and catabolic ornithine transcarbamylase
      and by a membrane-bound arginine-ornithine antiporter. Recently we reported the
      characterization of catabolic ornithine transcarbamylase and the corresponding
      gene, arcB, from Halobacterium salinarium (formerly Halobacterium halobium).
      Upstream of the arcB gene, three additional open reading frames with
      halobacterial codon usage were found. They were identified as the arcC gene
      coding for carbamate kinase, the arcA gene coding for arginine deiminase, and a
      gene, tentatively termed arcR, coding for a putative regulatory protein. The
      identification of the arcC and arcA genes was verified, respectively, by
      heterologous expression of the enzyme in Haloferax volcanii and by protein
      isolation and N-terminal sequence determination of three peptides. The gene order
      arcRACB differs from the gene order arcDABC in Pseudomonas aeruginosa, the only
      other organism for which sequence information is available. Transcripts from H.
      salinarium cultures grown fermentatively or aerobically were characterized by
      Northern (RNA) blot and primer extension analyses. It was determined (i) that
      monocistronic transcripts corresponding to the four open reading frames exist and
      that there are three polycistronic transcripts, (ii) that the level of induction
      during fermentative growth differs for the various transcripts, and (iii) that
      upstream of the putative transcriptional start sites for the three structural
      genes there are sequences with similarities to the halobacterial consensus
      promoter. The data indicate that expression of the arc gene cluster and its
      regulation differ in H. salinarium and P. aeruginosa.

PMID- 8759860
TI  - Structure of the low-affinity penicillin-binding protein 5 PBP5fm in wild-type
      and highly penicillin-resistant strains of Enterococcus faecium.
AB  - Among its penicillin-binding proteins (PBPs), Enterococcus faecium possesses a
      low-affinity PBP5, PBP5fm, which is the main target involved in beta-lactam
      resistance. A 7.7-kb EcoRI chromosomal fragment of E. faecium D63r containing the
      pbp5fm gene was cloned and sequenced. Two open reading frames (ORFs) were found.
      A 2,037-bp ORF encoded the deduced 73.8-kDa PBP5fm, the amino acid sequences of
      which were, respectively, 99.8, 78.5, and 62% homologous to those of the low
      affinity plasmid-encoded PBP3r of Enterococcus hirae S185r and the chromosome
      encoded PBP5 of E. hirae R40 and Enterococcus faecalis 56R. A second 597-bp ORF,
      designated psrfm, was found 2.3 kb upstream of pbp5fm. It appeared to be 285 bp
      shorter than and 74% homologous with the regulatory gene psr of E. hirae ATCC
      9790. Different clinical isolates of E. faecium, for which a wide range of
      benzylpenicillin MICs were observed, showed that the increases in MICs were
      related to two mechanisms. For some strains of intermediate resistance (MICs of
      16 to 64 micrograms/ml), the increased level of resistance could be explained by
      the presence of larger quantities of PBP5fm which had an affinity for
      benzylpenicillin (second-order rate constant of protein acylation [k+2/K] values
      of 17 to 25 M(-1) s(-1)) that remained unchanged. For the two most highly
      resistant strains, EFM-1 (MIC, 90 micrograms/ml) and H80721 (MIC, 512
      micrograms/ml), the resistance was related to different amino acid substitutions
      yielding very-low-affinity PBP5fm variants (k+2/K < or = 1.5 M(-1) s(-1)) which
      were synthesized in small quantities. More specifically, it appeared, with a
      three-dimensional model of the C-terminal domain of PBP5fm, that the
      substitutions of Met-485, located in the third position after the conserved SDN
      triad, by Thr in EFM-1 and by Ala in H80721 were the most likely cause of the
      decreasing affinity of PBP5fm observed in these strains.

PMID- 8759861
TI  - Cloning and characterization of nnrR, whose product is required for the
      expression of proteins involved in nitric oxide metabolism in Rhodobacter
      sphaeroides 2.4.3.
AB  - During denitrification, the production and consumption of nitric oxide (NO), an
      obligatory and freely diffusible intermediate, must be tightly regulated in order
      to prevent accumulation of this highly reactive nitrogen oxide. Sequencing
      upstream of norCB, the structural genes for NO reductase, in the denitrifying
      bacterium Rhodobacter sphaeroides 2.4.3, we have identified a gene, designated
      nnrR, which encodes a protein that is a member of the cyclic AMP receptor family
      of transcriptional regulators. Insertional inactivation of nnrR prevents growth
      on nitrite, as well as the reduction of nitrite and NO, but has no effect on
      reduction of nitrate or photosynthetic growth. By using nirK-lacZ and norB-lacZ
      fusions, we have shown that NnrR is a positive transcriptional regulator of these
      genes. nnrR is expressed at a low constitutive level throughout the growth of R.
      sphaeroides 2.4.3. These results show that NnrR is not a global regulator but is
      instead a regulator of genes whose products are directly responsible for
      production and reduction of NO. Evidence is also presented suggesting that an
      NnrR homolog may be present in the nondenitrifying bacterium R. sphaeroides
      2.4.1. The likely effector of NnrR activity, as determined on the basis of work
      detailed in this paper and other studies, is discussed.

PMID- 8759863
TI  - Identification and characterization of the origin of conjugative transfer (oriT)
      and a gene (nes) encoding a single-stranded endonuclease on the staphylococcal
      plasmid pGO1.
AB  - The genes mediating the conjugative transfer of the 52-kb staphylococcal plasmid
      pGO1 are within a 14.4-kb gene cluster designated trs. However, a clone
      containing trs alone cannot transfer independently and no candidate oriT has been
      found within or contiguous to trs. In this study, we identified a 1,987-bp open
      reading frame (ORF) 24 kb 3' and 13 kb 5' to trs that was essential for
      conjugative transfer: transposon insertions into the ORF abolished transfer and a
      plasmid containing the ORF could complement these transposon-inactivated pGO1
      mutants for transfer. Analysis of the nucleotide sequence of this ORF revealed
      significant homology between the amino terminus of its predicted protein and
      those of several single-stranded endonucleases. In addition, a 12-bp DNA sequence
      located 100 bp 5' to the ORF's translational start site was identical to the oriT
      sequences of the conjugative or mobilizable plasmids RSF1010, pTF1, R1162,
      pSC101, and pIP501. The ability of the ORF, designated nes (for nicking enzyme of
      staphylococci), to generate a single-stranded nick at the oriT was demonstrated
      in Escherichia coli by alkaline gel and DNA sequence analysis of open circular
      plasmid DNA. Plasmids that could be converted to the open circular form by the
      presence of oriT and nes could also be mobilized at high frequency into
      Staphylococcus aureus recipients with a second plasmid containing only trs. We
      propose that the 14.4 kb of trs and the approximately 2.2 kb of the oriT-nes
      region, coupled with an origin of replication, make up the minimal staphylococcal
      conjugative replicon.

PMID- 8759864
TI  - SpoIIE mutants of Bacillus subtilis comprise two distinct phenotypic classes
      consistent with a dual functional role for the SpoIIE protein.
AB  - Mutations in the spoIIE locus of Bacillus subtilis block sporulation at the stage
      of asymmetric septation and prevent compartment-specific activation of the
      transcription factor delta F. Recent ultrastructural studies of spoIIE mutants
      led to the conclusion that cells blocked at the stage of asymmetric septation
      form primarily thick septal structures similar to those formed at the mid-cell
      site during vegetative growth, although in an earlier study Piggot (J. Bacteriol.
      114:1241-1253, 1973) clearly detected a more complex range of phenotypes. We have
      examined the phenotypes of six spoIIE mutants, including one example of the
      previously studied null type, spoIIE21. We confirmed that the spoIIE21 mutant and
      two other null mutants exhibit the classic thick-septum phenotype. However, two
      of the missense mutants, the spoIIE64 and spoIIE71 mutants, were found to display
      a strikingly different phenotype characterized by the presence of only thin
      asymmetric septa, frequently at both polar positions, as noted by Piggot. This
      phenotype is essentially identical to those of spoIIA (delta F) and spoIIG (delta
      E) null mutants, which also form sporulation septa that appear structurally
      normal at the level of electron microscopy. Despite the formation of apparently
      normal asymmetric septa, spoIIE64 and spoIIE71 mutants are fully defective in
      activation of delta F-dependent gene expression. These results indicate that the
      functional roles performed by SpoIIE in septum assembly and sigma factor
      regulation are distinct and separable.

PMID- 8759862
TI  - Preponderance of Fis-binding sites in the R6K gamma origin and the curious effect
      of the penicillin resistance marker on replication of this origin in the absence
      of Fis.
AB  - Fis protein is shown here to bind to 10 sites in the gamma origin of plasmid R6K.
      The Fis-binding sites overlap all the previously identified binding sites in the
      gamma origin for the plasmid-encoded pi initiator protein and three host-encoded
      proteins, DnaA, integration host factor, and RNA polymerase. However, the
      requirement of Fis for R6K replication depends on the use of copy-up pi-protein
      variants and, oddly, the antibiotic resistance marker on the plasmid. In Fis
      deficient cells, copy-up pi variants cannot drive replication of R6K gamma-origin
      plasmids carrying the bla gene encoding resistance to penicillin (Penr) but can
      drive replication of plasmids with the same origin but carrying the
      chloramphenicol acetyltransferase gene encoding chloramphenicol resistance (Cmr).
      In contrast, R6K replication driven by wild-type pi is unaffected by the
      antibiotic resistance marker in the absence of Fis protein. Individually, none of
      these elements (copy-up pi, Fis deficiency, or drug markers) prevents R6K
      replication. The replication defect is not caused by penicillin in the medium or
      runaway replication and is unaffected by the orientation of the bla gene relative
      to the origin. Replication remains inhibited when part of the bla coding segment
      is deleted but the bla promoter is left intact. However, replication is restored
      by insertion of transcriptional terminators on either side of the gamma origin,
      suggesting that excess transcription from the bla gene may inactivate replication
      driven by pi copy-up mutants in the absence of Fis. This study suggests that
      vector sequences such as drug markers may not be inconsequential in replication
      studies, as is generally assumed.

PMID- 8759865
TI  - Sigma factor-anti-sigma factor interaction in alginate synthesis: inhibition of
      AlgT by MucA.
AB  - Conversion from the nonmucoid to the mucoid phenotype is a typical feature of
      Pseudomonas aeruginosa strains causing chronic pulmonary infections in cystic
      fibrosis patients. One of the key genetic controls in this conversion to mucoidy
      is from the algT(U)-mucA-mucB(algN) locus, located at 67.5 min on the standard P.
      aeruginosa chromosomal map. The algT gene promotes conversion to mucoidy and
      encodes an alternative sigma factor (sigma E) which belongs to the ECF (for
      extracytoplasmic function) family. On the other hand, the mucA and mucB (algN)
      genes suppress conversion to mucoidy. Loss-of-function mutations in mucA have
      been postulated to be the cause of mucoidy in some P. aeruginosa strains isolated
      from cystic fibrosis patients. We expressed and purified the protein products
      from the mucA and mucB open reading frames. The purified MucA protein abolishes
      the in vitro transcription specified by AlgT and the ability of AlgT to compete
      with an Escherichia coli sigma factor, FliA, suggesting that inhibiting AlgT
      dependent transcription could be the mechanism by which mucA suppresses mucoidy
      in vivo. Enzyme-linked immunosorbent assay and glycerol density gradient
      sedimentation experiments suggest that MucA physically interacts with AlgT.

PMID- 8759866
TI  - Control of AlgU, a member of the sigma E-like family of stress sigma factors, by
      the negative regulators MucA and MucB and Pseudomonas aeruginosa conversion to
      mucoidy in cystic fibrosis.
AB  - The alternative sigma factor AlgU (Pseudomonas aeruginosa sigma E) is required
      for full resistance of P. aeruginosa to oxidative stress and extreme
      temperatures. AlgU also controls conversion of P. aeruginosa to the mucoid,
      alginate-overproducing phenotype associated with lethal infections in cystic
      fibrosis patients. Mutations that cause conversion to mucoidy in cystic fibrosis
      isolates occur frequently in mucA, the second gene within the algU mucABCD gene
      cluster. Here we analyze the biochemical basis of conversion to mucoidy. MucA was
      shown to act as an anti-sigma factor by binding to AlgU and inhibiting its
      activity. MucB, another negative regulator of AlgU, was localized in the
      periplasm. MucB exerts its function from this compartment, since deletion of the
      leader peptide and the cytoplasmic location of MucB abrogated its ability to
      inhibit mucoidy. These data support a model in which a multicomponent system,
      encompassing an anti-delta factor and elements in the periplasmic compartment,
      modulates activity of AlgU. Since factors controlling AlgU are conserved in other
      gram-negative bacteria, the processes controlling conversion to mucoidy in P.
      aeruginosa may be applicable to the regulation of AlgU (sigma E) equivalents in
      other organisms.

PMID- 8759867
TI  - Sequence analysis and identification of the pyrKDbF operon from Lactococcus
      lactis including a novel gene, pyrK, involved in pyrimidine biosynthesis.
AB  - Three genes encoding enzymes involved in the biosynthesis of pyrimidines have
      been found to constitute an operon in Lactococcus lactis. Two of the genes are
      the well-known pyr genes pyrDb and pyrF, encoding dihydroorotate dehydrogenase
      and orotidine monophosphate decarboxylase, respectively. The third gene encodes a
      protein which was shown to be necessary for the activity of the pyrDb-encoded
      dihydroorotate dehydrogenase; we propose to name the gene pyrK. The pyrK-encoded
      protein is homologous to a number of proteins which are involved in electron
      transfer. The lactococcal pyrKDbF operon is highly homologous to the
      corresponding part of the much-larger pyr operon of Bacillus subtilis. orf2, the
      pyrK homolog in B. subtilis, has also been shown to be necessary for pyrimidine
      biosynthesis (A. E. Kahler and R. L. Switzer, J. Bacteriol. 178:5013-5016, 1996).
      Four genes adjacent to the operon, i.e., orfE, orfA, orfC, and gidB, were also
      sequenced. Three of these were excluded as members of the pyr operon by
      insertional analysis (orfA) or by their opposite direction of transcription (orfE
      and gidB). orfC, however, seems to be the distal gene in the pyrKDbF-orfC operon.

PMID- 8759868
TI  - Identification of a novel gene of pyrimidine nucleotide biosynthesis, pyrDII,
      that is required for dihydroorotate dehydrogenase activity in Bacillus subtilis.
AB  - An in-frame deletion in the coding region of a gene of previously unidentified
      function (which is called orf2 and which we propose to rename pyrDII) in the
      Bacillus subtilis pyr operon led to pyrimidine bradytrophy, markedly reduced
      dihydroorotate dehydrogenase activity, and derepressed levels of other enzymes of
      pyrimidine biosynthesis. The deletion mutation was not corrected by a plasmid
      encoding pyrDI, the previously identified gene encoding dihydroorotate
      dehydrogenase, but was complemented by a plasmid encoding pyrDII. We propose that
      pyrDII encodes a protein subunit of dihydroorotate dehydrogenase that catalyzes
      electron transfer from the pyrDI-encoded subunit to components of the electron
      transport chain.

PMID- 8759869
TI  - Expression of the structural gene, laf1, encoding the flagellin of the lateral
      flagella in Azospirillum brasilense Sp7.
AB  - The induction of the lateral flagella of Azospirillum brasilense Sp7 was studied
      by using a translational fusion between the laf1 promoter and gusA. The fusion
      was induced when cells were grown on solid media but not when they were grown in
      broth. The fusion was also induced by incubation of liquid-grown cells with an
      anti-polar flagellum polyclonal antiserum. Hindrance of polar-flagellum rotation
      is suggested to be the signal for this induction.

PMID- 8759870
TI  - Analysis of Fur binding to operator sequences within the Neisseria gonorrhoeae
      fbpA promoter.
AB  - The gene encoding Neisseria gonorrhoeae periplasmic binding protein FbpA contains
      two regions whose sequences exhibit homology with the Escherichia coli ferric
      uptake regulator protein (Fur) consensus binding sequence. In this study, DNase I
      footprinting experiments were employed to characterize the operator sequences
      within the fbpA promoter region to which E. coli Fur binds. A 160-bp fragment
      encompassing the promotor region and the putative iron boxes of the fbpA promoter
      was incubated with Fur, DNaseI was added, and the products of these reactions
      were sequenced to identify nucleotide peaks that were protected. At 50 nM Fur, a
      protected region that spanned 33 bp and extended 19 bp upstream and 8 bp
      downstream of the -35 region of the fbpA promoter was observed. At higher
      concentrations of Fur (75 and 100 nM), an extension of this protected region
      upstream of the -35 region was observed. Introduction of a plasmid carrying an
      fbpA-cat transcriptional fusion in E. coli H1717 (Fur+) resulted in an 88%
      induction of chloramphenicol acetyltransferase expression under conditions of
      iron restriction; however, chloramphenicol acetyltransferase expression was not
      responsive to iron in E. coli H1745 (Fur-), indicating that transcriptional
      regulation of fbpA in response to iron occurs via the negative regulator Fur. The
      extent of the fbpA operator sequence (42 bp), as defined by our footprinting
      analysis, would suggest the binding of two Fur repressor dimers.

PMID- 8759871
TI  - Effect of viscosity on swimming by the lateral and polar flagella of Vibrio
      alginolyticus.
AB  - By using mutants of Vibrio alginolyticus with only a polar flagellum (Pof+ Laf-)
      or only lateral flagella (Pof- Laf+), we examined the relationship between
      swimming speed and the viscosity of the medium for each flagellar system. Pof+
      Laf- cells could not swim in the high-viscosity environment (ca. 200 cP) in which
      Pof- Laf+ cells swam at 20 microns/s. The Pof- Laf+ cells swam at about 20
      microns/s at normal viscosity (1 cP) without the viscous agent, and the speed
      increased to 40 microns/s at about 5 cP and then decreased gradually as the
      viscosity was increased further. These results show the functional difference
      between polar and lateral flagella in viscous environments.

PMID- 8759872
TI  - Isolation and characterization of the structural gene for OmpL, a pressure
      regulated porin-like protein from the deep-sea bacterium Photobacterium species
      strain SS9.
AB  - Transposon-directed cloning was used to isolate the ompL gene from the deep-sea
      bacterium Photobacterium species strain SS9. The deduced amino acid sequence of
      OmpL displays sequence homology to porin proteins from enteric bacteria. Gene
      fusion and primer extension analyses indicate that ompL is transcriptionally
      regulated by pressure.

PMID- 8759874
TI  - Identification of additional genes under the control of the transcription factor
      sigma F of Bacillus subtilis.
AB  - We describe the identification of five transcriptional units under the control of
      the sporulation transcription factor sigma F in Bacillus subtilis. These are
      csfA, csfB, csfC, csfD, and csfF, located at approximately 230 degrees, 2
      degrees, 316 degrees, 205 degrees, and approximately 290 degrees, respectively,
      on the genetic map. Null mutations in csfA, csfB, csfC, or csfD, either alone or
      together, do not cause a noticeable defect in sporulation or germination.

PMID- 8759873
TI  - Proteome of Salmonella typhimurium SL1344: identification of novel abundant cell
      envelope proteins and assignment to a two-dimensional reference map.
AB  - Forty-nine cell envelope proteins of Salmonella typhimurium SL1344 have been
      identified by microsequencing and assigned to a two-dimensional reference map.
      Ten of the sequenced proteins appear to be novel. Several others closely match
      currently hypothetical proteins or proteins found in other bacteria but not
      previously reported in salmonellae.

PMID- 8759875
TI  - Single-stranded DNA-binding protein enhances the stability of CTG triplet repeats
      in Escherichia coli.
AB  - The stability of CTG triplet repeats was analyzed in Escherichia coli to identify
      processes responsible for their genetic instability. Using a biochemical assay
      for stability, we show that the absence of single-stranded-DNA-binding protein
      leads to an increase in the frequency of large deletions within the triplet
      repeats.

PMID- 8759876
TI  - Escherichia coli DNA repair genes radA and sms are the same gene.
AB  - Escherichia coli strains carrying radA100 or sms mutations were identical in
      their sensitivities to either methyl methanesulfonate or UV radiation treatment
      and in their plasmid complementation patterns for UV radiation survival. DNA
      sequencing analysis of the radA mutant and radA+ strains and comparison of their
      sequences with the published sms gene sequence showed the radA mutant to differ
      only by a G-to-A transition mutation, which is predicted to change a cysteine in
      a zinc-finger motif to tyrosine. The sms gene is concluded to be identical to the
      previously described radA gene.

PMID- 8759877
TI  - A developmental stage-specific histone H1 homolog of Coxiella burnetii.
AB  - Two DNA-binding proteins have been detected in Coxiella burnetii by southwestern
      (DNA-protein) blotting. One of these, termed Hq1, is enriched in the small cell
      variant stage of the developmental cycle and displays compositional and primary
      amino acid sequence similarities to eukaryotic histone H1. C. burnetii appears to
      be another example of an intracellular parasite with morphologically distinct
      developmental forms whose nucleoid structure may be controlled by histone H1
      homologs.

PMID- 8759878
TI  - Identification of a second RcsA protein, a positive regulator of colanic acid
      capsular polysaccharide genes, in Escherichia coli.
AB  - A second form of RcsA, a positive activator of the capsular polysaccharide genes
      (cps), has been identified in Escherichia coli. Ferguson plot analysis suggests
      that the two RcsA proteins differ by size rather than by charge. Both RcsA
      proteins are expressed from a single rcsA gene. Detection of both RcsA proteins
      in delta lon cells is RcsB dependent.

PMID- 8759879
TI  - Multiple myeloma: almost all patients are cytogenetically abnormal.

PMID- 8759880
TI  - Activity of the ligand for c-mpl, thrombopoietin, in early haemopoiesis.
AB  - We examined the role of the ligand for c-mpl. thrombopoietin (TPO). in murine
      early haemopoiesis. using a serum-free culture system. TPO in combination with
      the ligand for c-kit (SF) or interleukin-3 (IL-3) supported colony formation by
      marrow cells of 5-fluorouracil (5-FU)-treated mice whereas TPO alone yielded no
      colony. When blast cell colonies grown in the presence of TPO plus SF or TPO plus
      IL-3 were individually replated in suspension cultures containing serum and
      several growth factors, various combinations of myeloid lineages were seen,
      indicating that the progenitors supported by TPO plus SF or TPO plus IL-3 are
      multipotential. Delayed addition experiments demonstrated that TPO has the
      potential to effectively support the survival of haemopoietic progenitors. We
      then studied the effects of TPO on proliferative kinetics of cycling progenitors.
      TPO hastened IL-3-dependent growth of progenitors by shortening the time required
      for cell cycling. These results suggest that TPO as a single factor, can support
      the survival of haemopoietic progenitors and TPO synergizes with SF or IL-3 to
      act on early multipotential haemopoietic progenitors.

PMID- 8759881
TI  - Haemopoietic growth factor tyrosine kinase receptor expression profiles in normal
      haemopoiesis.
AB  - Expression profiles were generated for the haemopoietic tyrosine kinase receptors
      (HGF-TKRs or class III TKRs) by PCR on cDNA samples (RT-PCR) using a degenerate
      primer set. Each profile consisted of primary and secondary, i.e. enriched for
      less-expressed sequences, fingerprints. This method was applied on FACS-purified
      haemopoietic CD34+ cells, both from bone marrow (BM) and umbilical cord blood
      (UCB), and on mature cells from peripheral blood. CD34+ BM cells showed
      expression of c-fms. flt3, whereas CD34+ UCB cells expressed c-fms and, to a
      lesser extent, c-kit and flt3. In mature blood cells, only c-fms was observed in
      monocytes and a weaker flt3 expression in monocytes and T lymphocytes, whereas no
      known class III TKRs were detected in B lymphocytes and polymorphonuclear cells
      (PMNs). In all fractions a novel band could be observed, which appeared to be
      RET. Expression of RET was confirmed by RT-PCR and showed the highest levels in
      monocytes, followed by PMNs and CD34+ cells. B lymphocytes revealed low levels of
      expression. RET is known to be essential in neural development. Our results
      suggest a possible role for this receptor in haemopoiesis.

PMID- 8759882
TI  - A possible change in doubling time of haemopoietic progenitor cells with stem
      cell development.
AB  - We separated haemopoietic progenitors derived from marrow cells of 5-fluorouracil
      (5-FU)-treated mice into three groups, based on the stages of stem cell
      development and studied doubling time, using a serum-free clonal culture system.
      Stage I progenitors were those present in primary marrow cells from 5-FU-treated
      mice. Stages II and III progenitors were early and late progenies in culture of
      stage I progenitors respectively. The morphological analysis of colonies derived
      from stage I, II and III progenitors demonstrated an association of progression
      of stages with loss of multipotentiality. The doubling time of haemopoietic
      progenitors was estimated by sequential analysis of colony formation and studies
      of growth fraction. The time required for haemopoietic progenitors to double
      shortened as their stage of development progressed. Alteration in one doubling
      time of haemopoietic progenitors at progressive stages of stem cell development
      was seen in cultures supported by various combinations of growth factors,
      including interleukin-3 (IL-3), IL-11. and steel factor (SF), Cell-cycle analysis
      suggested that reduction of the doubling time of haemopoietic progenitors is
      probably due to a decrease in the time spent in the G1 phase of the cell cycle.
      Our results suggest that in early haemopoiesis the doubling time of haemopoietic
      progenitors may change with stem cell development.

PMID- 8759883
TI  - Constitutive expression of granulocyte-colony stimulating factor receptor on a
      human B-lymphoblastoid cell line.
AB  - The present study demonstrated that a human B-cell line derived from non
      Hodgkin's lymphoma. HCF-MLpN. constitutively expressed G-CSF receptor on the cell
      surface. G-CSF binding to the cell surface was shown by immunofluorescence
      staining using biotinylated G-CSF preparation and analysed by flow cytometry.
      Specific binding of G-CSF to the cells was shown by pretreatment with unlabelled
      G-CSF. In the radioreceptor assay and Scatchard plot analysis using radiolabelled
      ligand, MLpN cells revealed a single species of binding site with an equilibrium
      dissociation constant of 167 (153-182) pM and a maximal binding site per cell of
      1076 (1044-1116). The G-CSF receptor mRNA transcript was exhibited in the RNA
      from MLpN cells by reverse transcriptase polymerase chain reaction procedure.
      [3H]thymidine incorporation and trypan blue exclusion showed that the G-CSF
      receptor was capable of transducing the growth signal to HCF-MLpN cells. A small
      fraction of fresh B blasts from six patients with B-cell lymphoma and leukaemia
      displayed G-CSF binding by two-colour immunofluorescence staining. In contrast, a
      panel of seven B-cell lines was negative for the binding to biotinylated G-CSF
      preparation. These results suggest that the phenotype of G-CSF binding may be
      lost during the culture. The expression of G-CSF receptor in HCF-MLpN cells
      appeared to be exceptional.

PMID- 8759884
TI  - Cryopreserved human bone marrow stroma is fully functional in vitro.
AB  - Human-marrow long-term culture (LTC) enables maintenance of both stromal and
      haemopoietic elements of normal bone marrow (NBM) in vitro for 4-6 months. Stroma
      based cultures are critical for quantitation of long-term culture initiating
      cells (LTC-IC), the most primitive human haemopoietic cells measurable in vitro.
      Supply of NBM can be sporadic, and up to 3-4 weeks in culture is required for
      stromal maturity. Stroma availability for experimental purposes can therefore be
      limited. Efforts to produce transformed human and transfected murine stromal cell
      lines comparable to NBM stroma have had some success. As an alternative, we
      investigated cryopreserved NBM and cryopreserved performed stroma. Function of
      cryopreserved and control fresh NBM stroma was similar when evaluated for up to
      12 weeks in LTC. We have also demonstrated that stroma derived from cryopreserved
      NBM or performed cryopreserved NBM stroma can sustain third-party haemopoiesis as
      efficiently as fresh NBM stroma in LTC. Batched cryopreserved stroma is a
      convenient, rapidly available, source of functional stroma which avoids the
      logistic difficulties and lack of standardization associated with stroma from
      fresh NBM. This important advance will enhance the use of stroma-based LTC in
      studies of human haemopoiesis.

PMID- 8759885
TI  - The behaviour of red cells in narrow tubes in vitro as a model of the
      microcirculation.
AB  - To investigate the behaviour of red cells in the microcirculation, we established
      a new capillary method using narrow fluorinated ethylenepropylene copolymer tubes
      with internal diameters of 12.5 and 25.0 microns. Red cell flow in the tubes
      under a given range of pressure was analysed through a video system connected to
      a microscope. The experimental condition was adjusted so that the velocity of the
      control normocytes would be compatible with that in corresponding vessels in
      vivo, 0.5-1.5 mm/s. In the 12.5 microns tube, normocytes obtained from 12 young
      normal volunteers ran in an axisymmetric edge-on orientation with a folded shape
      at higher pressures, but rolled along freely without deformation at lower
      pressures. Deformation during the passage of the microcytes obtained from four
      patients with polycythaemia vera complicated with iron-deficient microcytosis and
      10 patients with iron deficiency anaemia was relatively mild, whereas that of the
      macrocytes obtained from eight patients with refractory anaemia was marked. Even
      after the screening effect at the tube entrance was taken into consideration, the
      velocities of both microcytes and macrocytes were found to be significantly lower
      than the control normocytes. Therefore this method may be a new way to
      investigate the flow properties of red cells in the microcirculation.

PMID- 8759886
TI  - Isolated beta-globin chains reproduce, in normal red cell membranes, the
      defective binding of spectrin to alpha-thalassaemic membranes.
AB  - Alpha-thalassaemic erythrocytes develop a specific membrane skeletal defect that
      is manifest as a loss of normal spectrin-binding sites on the inner surface of
      the thalassaemic membranes. To test whether this lesion could be caused by the
      excess free beta-globin chains that accumulate in alpha-thalassaemic red cells,
      we incubated normal red cell membranes with native, haem-containing alpha or beta
      globin chains or with haemoglobin A. Spectrin-depleted inside-out membrane
      vesicles (IOVs) derived from membranes incubated with beta-globin chains bound
      only 9 +/- 3% as much spectrin as IOVs from control membranes incubated with
      bovine serum albumin. In contrast. IOVs from membranes incubated with alpha
      globin chains or haemoglobin A were nearly normal (79 +/- 3% and 86 +/- 5% of
      controls, respectively). This differential effect of globin chains was not seen
      when membranes were first transformed into spectrin-depleted IOVs and then
      incubated with the isolated globin chains. Under these conditions, both alpha and
      beta globin chains reduced the spectrin-binding capacity of the IOVs by
      approximately 45% (alpha 46 +/- 7%, beta 43 +/- 6%) whereas haemoglobin A had no
      effect. Unlike IOVs, spectrin isolated from membranes exposed to alpha or beta
      globin chains bound normally to IOVs and to actin (in the presence of protein
      4.1). These studies show that isolated beta-globin chains (but not alpha-globin
      chains) can produce a spectrin-binding defect in normal red cell membranes
      similar to that seen in alpha thalassaemia. The existence of similar defects in
      the membrane skeletons of red cells from other diseases with unstable beta
      globins suggests a common pathophysiology for the premature destruction of these
      cells.

PMID- 8759887
TI  - Haematological abnormalities in Shwachman-Diamond syndrome.
AB  - We have analysed the haematological parameters in 21 patients with Shwachman
      Diamond syndrome (SDS) seen over a 25-year period at our institution.
      Neutropenia, although present in all patients, was intermittent in two-thirds,
      constant in the rest and was associated with impaired chemotaxis in all of those
      patients tested. Fetal haemoglobin (HbF) was elevated in 80% of the patients at
      some stage, and anaemia and thrombocytopenia was documented in 66% and 24%
      respectively. Bone marrow samples were taken in over half of the patients.
      Myelodysplastic syndrome (MDS) developed in seven (33%) patients, five of whom
      had acquired clonal structural chromosome abnormalities in their bone marrows. In
      five of the patients with MDS (24%) transformation to acute myeloid leukaemia
      occurred. Like other constitutional bone marrow failure syndromes. SDS has a
      predilection to leukaemic transformation hitherto assumed to be in the region of
      5-10%. The data presented here suggest that this figure probably represents an
      underestimate. Shwachman-Diamond syndrome is an interesting model of leukaemia
      development and greater understanding of the clinical spectrum of this rare
      disorder should produce further insights into its pathobiology.

PMID- 8759888
TI  - Second transplantation using allogeneic peripheral blood stem cells in a beta
      thalassaemia major patient featuring stable mixed chimaerism.
AB  - Allogeneic bone marrow transplantation (BMT) for beta-thalassaemia major carries
      the risks of disease recurrence due to residual thalassaemic stem cells or true
      immune-mediated rejection. We report a thalassaemic patient who displayed stable
      mixed chimaerism with only 5% donor-derived cells for about 5 years after BMT.
      Displacement of host cells was accomplished by ambulatory non-myeloablative
      conditioning and allogeneic G-CSF mobilized peripheral blood stem cell
      transplantation from the same donor, resulting in full reconstitution. Patients
      featuring stable mixed chimaerism after BMT may benefit from allogeneic cell
      therapy with immunocompetent lymphocytes and stem cells, whilst avoiding
      supralethal conditioning.

PMID- 8759889
TI  - The effect of iron chelation on haemopoiesis in MDS patients with transfusional
      iron overload.
AB  - Long-term follow-up data are presented on changes in peripheral blood counts and
      Hb requirements of 11 patients with myelodysplastic syndromes (MDS) during iron
      chelation treatment with desferrioxamine for up to 60 months. The erythroid
      marrow activity was indirectly evaluated by repeated determinations of the serum
      transferrin receptor concentration. The efficacy of iron chelation was evaluated
      by repeated quantitative determination of the liver iron concentration by
      magnetic resonance imaging. Reduction in the Hb requirement ( > or = 50%) was
      seen in 7/11 (64%) patients. Five patients (46%) became blood transfusion
      independent. Platelet counts increased in 7/11 (64%) patients and the neutrophil
      counts in 7/9 (78%) evaluable patients. All patients in whom iron chelation was
      highly effective showed improvement of erythropoietic output accompanied by an
      increase in the serum transferrin receptor concentration. It is concluded that
      reduction in cytopenia in MDS patients may be accomplished by treatment with
      desferrioxamine, if the iron chelation is efficient and the patients are treated
      for a sufficiently long period of time. Exactly how treatment with
      desferrioxamine works remains a challenge for further investigation.

PMID- 8759890
TI  - Neutralizing anti-interferon-alpha antibodies and response to treatment in
      patients with Ph+ chronic myeloid leukaemia sequentially treated with recombinant
      (alpha 2a) and lymphoblastoid interferon-alpha.
AB  - Neutralizing anti-IFN alpha antibodies (nIFN alpha Abs) occur in a significant
      proportion of patients with hairy cell leukaemia, hepatitis or solid tumours
      treated with recombinant IFN alpha (IFN alpha 2a or IFN alpha 2b), but
      information on their incidence in chronic myeloid leukaemia (CML) is scanty and
      their clinical relevance is not yet completely defined. By using an IFN alpha
      antiviral neutralization bioassay, the frequency of nIFN alpha 2a Abs was
      evaluated in 67Ph+ CML patients during IFN alpha 2a therapy at doses ranging from
      6 to 9 MU/d. 15 patients (22%) developed nIFN alpha 2a Abs (titre ranging from
      1:40 to 1:20480) and 11/15 (73%) were haematologically and/or karyotypically
      unresponsive to treatment. 52 patients did not develop antibodies and 11 of them
      (21%) were unresponsive. The negative relationship between the positivity for
      nIFN alpha 2a Abs and the response to treatment was highly significant (P =
      0.0001). In nine nIFN alpha 2a Abs positive patients, treatment was changed from
      recombinant IFN alpha 2a to lymphoblastoid IFN alpha (IFN alpha-ly), at the same
      dose and schedule. After 9 months of IFN alpha-ly treatment a haematological
      response was achieved in 4/7 cases who were non-responsive to prior IFN alpha 2a
      therapy and was maintained in the other two patients previously responsive to IFN
      alpha 2a. However, no karyotypic response was observed. This data shows that a
      significant proportion of Ph+ CML patients receiving treatment with IFN alpha 2a
      can develop neutralizing antibodies and that these antibodies are associated with
      a loss of IFN alpha 2a efficacy. Changing the patients to treatment with
      lymphoblastoid IFN alpha may restore haematological response but it is not likely
      to induce a karyotypic response.

PMID- 8759891
TI  - Analysis of the kappa light chain variable region in multiple myeloma.
AB  - The study of immunoglobulin heavy chain gene rearrangements in multiple myeloma
      has revealed extensive divergence from the germline sequences, but no intraclonal
      diversity with disease evolution. Our study investigated the state of the
      rearranged kappa light chain variable region (V kappa) gene segments as well as
      abortive V kappa family gene usage in cases of multiple myeloma expressing lambda
      light chain. We studied 11 cases of kappa and five cases of lambda light chain
      expressing multiple myeloma. Total cellular RNA was extracted from the bone
      marrow of patients with overt disease and subjected to reverse transcription
      polymerase chain reaction (RT-PCR) analysis to amplify clonally rearranged
      variable region sequences. Direct nucleotide sequencing by the dideoxy-chain
      termination method was performed on the RT-PCR products. We did not observe
      preferential usage of certain V kappa gene families. Mutation frequencies of the
      V kappa segments varied in number. In the majority of cases, extensive somatic
      mutations occurred within the complementarity determining regions (CDRs) of V
      kappa, whereas only a limited degree of divergence from the germline was observed
      in others. In all cases studied. replacement mutations tended to cluster in the
      CDRs, a finding compatible with an antigen-driven somatic hypermutation process.
      In 3/5 cases of lambda light-chain expressing multiple myeloma, abortively
      rearranged V kappa gene segments were amplified from genomic DNA; in two cases a
      non-templated nucleotide insertion rendering the V kappa sequences out-of-frame
      was observed, and in the third a stop codon was identified in the open reading
      frame of the V kappa sequence. Somatic mutations were observed in all cases of
      abortive V kappa genes studied; however, their distribution does not suggest
      selection by antigen. We conclude that somatic mutations observed in the V kappa
      regions of myeloma cells are of variable extent and suggest operation of the
      antigen selection process. Lack of or minimal somatic hypermutation in a few
      cases may be in some way implicated in the biological heterogeneity of the
      disease.

PMID- 8759892
TI  - A plasmocyte selective monoclonal antibody (B-B4) recognizes syndecan-1.
AB  - We developed a new monoclonal antibody. B-B4, which specifically identifies human
      plasma cells. It strongly reacts with all multiple myeloma cell lines and with
      malignant plasma cells of all tumour samples of the multiple myeloma patients
      tested. B-B4 does not react with any peripheral blood, bone marrow or tonsil
      cells. Cloning of the B-B4 antigen reveals that the monoclonal antibody
      recognizes syndecan-1. It appears that the monoclonal antibody B-B4 is a suitable
      marker for human plasmocyte identification among haemopoietic cells and a useful
      probe for the diagnosis of haematological malignancies. Furthermore, this
      monoclonal antibody can be used for depletions prior to CD34 grafting.

PMID- 8759893
TI  - Effect of interferon on the health-related quality of life of multiple myeloma
      patients: results of a Nordic randomized trial comparing melphalan-prednisone to
      melphalan-prednisone + alpha-interferon. The Nordic Myeloma Study Group.
AB  - In a Nordic multi-centre trial, 583 previously untreated multiple myeloma
      patients were randomized to receive melphalan-prednisone or melphalan-prednisone+
      interferon alpha-2b at a dose of 5 million units subcutaneously, 3 d/week. A
      quality-of-life study was integrated into the trial, using the EORTC QLQ C-30
      questionnaire supplemented with 11 questions concerning interferon toxicity. The
      questionnaire was completed prior to treatment and after 1, 6, 12, 24, 36 and 48
      months. 90% of the patients participated in the quality-of-life study, and 83%
      completed all questionnaires submitted to them. During the first year of
      treatment the patients on interferon reported significantly more fever, chills,
      dry skin, fatigue, pain, nausea/vomiting and appetite loss than the control
      patients. There was a moderate reduction of the global quality-of-life score and
      slight, non-significant, reductions of physical, emotional, cognitive, social and
      role functioning scores. After the first year there were no statistically
      significant differences in any toxicity, symptom or quality-of-life score, except
      for an increased frequency of dizziness in the interferon group. As only 60% of
      the patients remained on interferon after 24 months, our data probably
      underestimate the potential toxicity of the drug. Although there was no
      significant survival benefit for the interferon patients, a 5-6 months
      prolongation of the response and plateau phase duration was observed. However, by
      intention-to-treat analysis, there was no late quality-of-life benefit for the
      interferon patients to compensate for the early impairment. Thus, the clinical
      significance of the plateau-phase prolongation is uncertain.

PMID- 8759894
TI  - Treatment of acute myelogenous leukaemia in patients aged 50-65: idarubicin is
      more effective than zorubicin for remission induction and prolonged disease-free
      survival can be obtained using a unique consolidation course. The Goelam Group.
AB  - From December 1987 to June 1992, 251 patients aged 50-65 with de novo acute
      myelogenous leukaemia (AML) were recruited to a multi-institutional randomized
      clinical trial. Induction therapy consisted of Ara-C (200 mg/ m2, continuous
      infusion, days 1-7) with either zorubicin (ZRB) (200 mg/m2, i.v., days 1-4) or
      idarubicin (IDR) (8 mg/ m2, i.v., days 1-5). Consolidation therapy consisted of a
      single course of intensive chemotherapy with high-dose Ara-C (3 g/m2, 3 h
      infusion, q 12 h, days 1-4) and m-Amsa (100 mg/m2/d, i.v., days 5-7). The
      complete remission (CR) rate was (73%) with Ara-C/ IDR versus (60%) with Ara
      C/ZRB (P = 0.033). In multivariate analysis, factors found to be significant in
      predicting CR were normal karyotype and treatment with IDR. With a median follow
      up of 73 months, the median disease-free survival (DFS) duration of all CR
      patients and the probability of CR at 6 years were 17 months and 29%. In
      multivariate analysis the only factor associated with an increased DFS duration
      was a normal karyotype. The median event-free survival (EFS) duration for all
      evaluable patients and the median overall survival duration for all eligible
      patients were respectively 7 and 12 months without any difference between
      induction arms. The study shows that in patients aged 50-65 idarabicin is more
      effective than zorubicin for remission induction. However, the type of
      anthracycline did not influence overall survival duration. Using a unique
      consolidation course, we observed a prolonged DFS which compares favourably with
      results obtained with more prolonged consolidation therapy or maintenance
      treatment.

PMID- 8759895
TI  - The retinoblastoma gene (rb1) in acute myeloid leukaemia: analysis of gene
      rearrangements, protein expression and comparison of disease outcome.
AB  - The occurrence of retinoblastoma gene abnormalities in a large subset of various
      malignancies suggests an important role for this tumour suppressor gene in
      carcinogenesis, but this varies considerably from one tumour type to another and
      results in patients with acute myeloid leukaemia (AML) have been controversial.
      We analysed 106 AML patients and 18 normal controls for RB1 gene rearrangements
      and 86 AML patients for RB protein (pRB) expression. Southern blot analysis
      detected no gross gene rearrangements, but several restriction enzyme
      polymorphisms were observed. By Western blot analysis, 20 patients (23%) had no
      detectable pRB protein and seven (8%) had truncated pRB bands. Discordance
      between the DNA and protein data suggests that there may be minor deletions and
      point mutations in the RB1 gene or abnormalities in the proteins regulating the
      expression of pRB. No significant differences in the frequency of attainment of
      complete remission or length of survival were observed between patients with
      normal and abnormal pRB.

PMID- 8759896
TI  - The ultrastructure of mantle cell lymphoma and other B-cell disorders with
      translocation t(11;14)(q13;q32).
AB  - We conducted an ultrastructural study in 22 cases of B-lymphoproliferative
      disorders in leukaemic phase bearing the t(11;14) translocation. The features of
      peripheral blood leukaemic cells in nine cases of mantle cell lymphoma (MCL) were
      compared to those diagnosed as B-prolymphocytic leukaemia (B-PLL) (five cases),
      splenic lymphoma with villous lymphocytes (SLVL) (four cases), lymphoplasmocytic
      lymphoma (LPL) (one case), chronic lymphocytic leukaemia with > 10%
      prolymphocytes (CLL/ PL) (one case) and unclassified B-non Hodgkin's lymphoma (B
      NHL) (two cases). The ultrastructural characteristics were also compared to those
      present in B-NHL without t(11;14), including cases of follicular centre lymphoma
      (FCL). This study shows that MCL has distinct ultrastructural features including
      a cleaved or indented nucleus with an even heterochromatin distribution, an
      absent or inconspicuous nucleolus, low N/C ratio, abundant mitochondria, a well
      developed Golgi zone, profiles of endoplasmic reticulum and centrioles. This
      pattern clearly differs from that found in FCL cells. The nuclear pattern of MCL
      cells also differed from the cells in the other disorders with t(11;14), but
      shared an organelle-rich cytoplasm, and features which were not apparent in cases
      without t(11;14). The cytoplasmic changes observed in cells bearing t(11;14)
      suggest increased cellular activity which may relate to the chromosome
      translocation and the resulting over-expression of bcl-1.

PMID- 8759897
TI  - Interferon-alpha 2b (IFN alpha) for early-phase chronic lymphocytic leukaemia
      with high risk for disease progression: results of a randomized multicentre
      study.
AB  - The efficacy of interferon-alpha 2b (IFN alpha) to prolong progression-free (PFS)
      and/or overall survival (OS) in early B-CLL (Binet stage A) was examined in a
      risk-adapted phase III study. 99 previously untreated B-CLL patients were
      recruited. 44 patients with expected high risk for disease progression, defined
      by non-nodular bone marrow infiltration and lymphocyte doubling time < or = 12
      months or serum thymidine kinase levels > or = 5 U/I, were randomized to either
      receive IFN alpha (group 1, n = 21) or not (group 2, n = 23). 55 low-risk
      patients were observed to evaluate this risk stratification (group 3). During a
      median observation time of 36 months, four patients in the IFN alpha group
      achieved a partial remission (PR), no patient had stable disease (SD), and 17
      patients experienced progressive disease (PD). The four responders had less
      extensive disease at study entry and tended to exhibit a rise in serum IgG
      levels. In group 2, no PR, seven SD and 16 PD, whereas in group 3, no PR, 37 SD
      and 18 PD occurred. PFS in group 1 (6.7 months) was not different from group 2
      (13.3 months, P = 0.22), but PFS of groups 1 and 2 differed from group 3 (37
      months, P < or = 0.001). OS was 44.9 months (group 1), 43.1 months (group 2) and
      57.9 months (group 3). OS was not significantly different for group 1 v 2, but
      was significant between groups 1 and 3 (P = 0.023). The higher percentage of PD
      in group 2 compared to group 3 (70% v 29%) shows that the selected risk factors
      allow the definition of CLL stage A patients at risk for disease progression
      within about a year. In conclusion, our data indicate that IFN alpha does not
      prolong PFS or OS in stage A CLL patients with high risk for disease progression.

PMID- 8759898
TI  - Elevated platelet count features the variant type of BCR/ABL junction in chronic
      myelogenous leukaemia.
AB  - A variant form of BCR/ABL junction was identified in a patient with chronic
      myelogenous leukaemia (CML). The BCR/ABL fusion mRNA of this patient showed in
      frame junction between BCR exon c3 and ABL exon 2. Although the diagnosis of CML
      was made, the patient showed clinical features of essential thrombocythaemia (ET)
      rather than that of typical CML. Treatment with interferon-alpha showed no
      cytogenetic response. The c3-a2 type of BCR/ABL junction seems to be associated
      with elevated platelet count and thus could form a novel clinical entity
      different from typical CML.

PMID- 8759899
TI  - Additional neoplasms and HCV infection in low-grade lymphoma of MALT type.
AB  - Several chronic inflammatory conditions and genetic alterations are likely to be
      involved in the pathogenesis of low-grade lymphoma of MALT type. In a well
      characterized series of 27 patients with low-grade lymphoma of MALT type, we
      studied: (1) the incidence of other neoplasms, which might be indicative of
      genetic instability, apparently a characteristic of this disease; (2) the
      prevalence of serologic and molecular markers of HCV infection, which has been
      found in association with other lymphoproliferative disorders. Three patients had
      one or more additional cancers; a total of eight tumours, five of which occurred
      in the same patient, suggests the presence of some genetic instability in at
      least some cases of the disease. Rather unexpectedly, anti-HCV antibodies and HCV
      RNA sequences were documented in 50% of the patients examined, without elevation
      of serum transaminases. Of interest, the two patients with parotid and
      conjunctival MALT lymphomas, respectively, with a previous history of Sjogren's
      syndrome, were HCV positive. We suggest, for the first time, that HCV may be
      considered, in addition to Helicobacter pylori, as another potential infectious
      co-factor in the multistep pathogenesis of low-grade lymphomas of MALT type.

PMID- 8759900
TI  - Clinical and molecular remission after allogeneic blood cell transplantation in a
      patient with mantle-cell lymphoma.
AB  - Mantle-cell lymphoma (MCL) is a B-cell tumour with a usually poor prognosis,
      characterized by the proliferation of small cleaved lymphocytes with a diffuse
      growth pattern. We report a polymerase chain reaction-based analysis of minimal
      residual disease in a patient who achieved complete remission after allogeneic
      blood cell transplantation (BCT). Rearrangement of the immunoglobulin heavy-chain
      genes was used to generate a lymphoma-specific molecular marker. Lymphoma cells
      were not detectable in a bone marrow sample collected 12 months after BCT. Our
      findings suggest that allogeneic BCT may offer a curative approach to MCL.

PMID- 8759901
TI  - An aggressive nasal lymphoma accompanied by high levels of soluble Fas ligand.
AB  - Fas ligand (FasL), either in the membrane bound form or soluble form, has
      cytotoxic activity against Fas-expressing cells. We report a case of nasal
      lymphoma accompanied by liver damage and pancytopenia. The serum level of soluble
      FasL (sFasL) was very high on admission, but rapidly decreased to normal levels
      after chemotherapy for lymphoma. Liver damage and pancytopenia also improved with
      the decrease in serum sFasL. Since Fas is expressed on both hepatocytes and
      haemopoietic cells, these facts suggest that FasL was expressed on lymphoma cells
      and directly associated with pathogenesis of liver damage and pancytopenia
      through its cytotoxic activity.

PMID- 8759902
TI  - Cryosupernatant as replacement fluid for plasma exchange in thrombotic
      thrombocytopenic purpura. Members of the Canadian Apheresis Group.
AB  - The current established treatment of thrombotic thrombocytopenic purpura (TTP) is
      plasma exchange with fresh frozen plasma (FEP). With this treatment, there is a
      49% response after seven exchanges and a 78% survival at 1 month. Although the
      exact cause of TTP is unknown, the presence of von Willebrand factor (VWF)
      multimers has been implicated in the disease. Accordingly, it has been suggested
      that cryosupernatant (plasma from which cryoprecipitate has been removed), which
      is relatively deficient in VWF multimers, might be an effective replacement fluid
      during plasma exchange. Patients from six centers were treated by plasma exchange
      with cryosupernatant. 18 patients who had failed a first course (average 7.7
      exchanges) of plasma exchange with FFP. received a further seven exchanges with
      cryosupernatant. Subsequently, 40 previously untreated patients were exchanged
      with cryosupernatant. Of the 18 previously treated patients, 11 responded
      (defined as an increase in platelet count to > 150 x 10(9) /1 and no neurological
      events) after seven exchanges and 15 (83%) of the patients were alive at 1 month.
      The response rate in the 40 previously untreated patients was 75% at the end of
      seven exchanges and 95% of the patients were alive at 1 month. These values are
      significantly different (P < 0.05) from those reported in our earlier study and
      in other patients concurrently treated at the same centres with FFP when
      cryosupernatant was not available. Some patients who have failed to respond to
      plasma exchange with FFP replacement will respond to further exchange with
      cryosupernatant. Cryosupernatant replacement may be more effective as first-line
      treatment of TTP than FFP.

PMID- 8759903
TI  - Recombinant human c-Mpl ligand is not a direct stimulator of proplatelet
      formation in mature human megakaryocytes.
AB  - To evaluate the effect of the c-Mpl ligand on platelet production by
      megakaryocytes, we investigated proplatelet formation in isolated human
      megakaryocytes cultured in serum-free medium, with or without the c-Mpl ligand,
      interleukin-6 and erythropoietin. When interleukin-6 was added to the culture
      medium, the percentage of megakaryocytes displaying proplatelets was
      approximately 1.5-fold the control value; whereas, in the presence of the c-Mpl
      ligand, the percentage of megakaryocytes displaying proplatelets decreased in a
      dose-dependent manner and did not increase compared to control values at any dose
      tested. However, the viability of megakaryocytes after a 4 d culture in the
      presence of the c-Mpl ligand was significantly higher than that of the cells
      cultured without it. The c-Mpl ligand did not stimulate the proplatelet formation
      in megakaryocytes in vitro.

PMID- 8759904
TI  - Mature micromegakaryocytes: an unusual developmental pattern in term infants.
AB  - We sought to gain perspective on platelet production in the fetus and the newborn
      by counting and characterizing megakaryocytes from available cord blood.
      Elutriation was used to isolate circulating megakaryocytes from umbilical
      arteries and veins obtained at scheduled caesarean sections of nine normal term
      fetuses. Megakaryocytes were identified by established criteria, their diameters
      measured, and maturation stages recorded. Large numbers of megakaryocytes, mostly
      mature, were found in both the umbilical arteries and veins, many times more than
      previously observed circulating in adult blood. In term infants more than a third
      of the mature megakaryocytes had unusually decreased nuclear lobation and were
      dwarf cells with diameters as small as 13 microns, which we considered to be
      micromegakaryocytes. The atypicality of these small but mature cells is seen as
      merely a leftward skewing in the development of megakaryocyte ploidies. We
      believe that in normal fetuses the extent of megakaryocyte ploidization and
      development is distinctive and probably regulated differently to the adult
      pattern.

PMID- 8759905
TI  - Mutations in a subgroup of patients with mild haemophilia A and a familial
      discrepancy between the one-stage and two-stage factor VIII:C methods.
AB  - A subgroup of patients with haemophilia A who have a familial discrepancy between
      the one-stage and two-stage factor VIII:C results has previously been described.
      These patients show factor VIII:C levels by one-stage assay that are 2-7-fold
      higher than their two-stage results. We have studied 10 such families and
      identified six different mutations in the factor VIII gene in this group. The
      chemical cleavage method and DNA sequencing was used to identify mutations in
      factor VIII gene fragments generated by reverse transcription and PCR. All
      available family members were tested to confirm the presence of the mutation in
      affected individuals. These patients were found to have one of six single point
      substitutions causing a missense mutation and alteration to one codon in exons 7,
      11, 14 or 18. The mutations comprise three that have not previously been
      described (Ala284Glu. Arg698Leu. Leu1932Phe) and three that have been previously
      described (Ser289Leu, Arg531His, Arg698Trp). Alterations to the amino acid
      composition of the A1, A2 and A3 domains of factor VIII are predicted by these
      molecular studies. In contrast, a control group of 23 mild haemophilia families
      with equivalent factor VIII:C results by one-stage and two-stage assays did not
      have any of the above mutations. Detailed studies in seven of these latter
      families identified four mutations affecting the A3, C1 and C2 domains of factor
      VIII. These findings suggest a genetic basis to the unusual factor VIII phenotype
      but do not explain the mechanism of the discrepant factor VIII activity.

PMID- 8759906
TI  - Age-related changes in factor VII proteolysis in vivo.
AB  - Previous studies have reported that pre-operative plasmas of patients over the
      age of 40 years who developed post-operative deep vein thrombosis (DVT) had
      approximately twice the amount of proteolysed factor VII found in plasmas of
      patients in whom prophylaxis with heparin or low M(r) heparin was successful.
      These and other studies also reported higher concentrations of thrombin
      antithrombin III in pre- and post-operative plasmas of patients who developed
      post-operative thrombosis than in plasmas of patients in whom prophylaxis was
      successful. Whether the extent of factor VII proteolysis seen in the patients who
      developed post-operative DVT is related to the severity of their disease or age
      is not known. This report investigated age-related changes in the concentrations
      of total factor VII protein, factor VII zymogen, factor VIIa, tissue factor
      pathway inhibitor, thrombin-antithrombin III, and prothrombin fragment 1 + 2 in
      normal plasmas and the relationships between these parameters. With the exception
      of thrombin-antithrombin III, statistically significant increases in the
      concentrations of these parameters with age were found. Additionally, the
      differences between the concentrations of total factor VII protein and factor VII
      zymogen, an index factor VII proteolysis in vivo, were statistically significant
      only for individuals over age 40. Using linear regression analysis, a significant
      correlation was found to exist between the concentrations of plasma factor VIIa
      and prothrombin fragment 1 + 2. Since factor VIIa-tissue factor probably
      initiates coagulation in vivo, we hypothesize that the elevated plasma factor
      VIIa (reflecting a less tightly regulated tissue factor activity and therefore
      increased thrombin production in vivo) accounts for the high risk for post
      operative thrombosis seen in individuals over the age of 40.

PMID- 8759907
TI  - Acute arterial thrombosis due to platelet aggregation in a patient receiving
      granulocyte colony-stimulating factor.
AB  - We describe a 44-year-old man with non-Hodgkin's lymphoma receiving granulocyte
      colony-stimulating factor (G-CSF) who developed an acute arterial thrombosis. The
      removed thrombus contained large amounts of platelet aggregation. A rapid
      increase of platelets and increased adenosine diphosphate (ADP)- and collagen
      induced platelet aggregation were observed at the time of the thrombotic event. A
      challenge test of G-CSF showed an increase in the platelet count and an
      augmentation of ADP- and collagen-induced platelet aggregation. In the use of
      GCSF. patients who produce a rapid increase in platelet levels could be at
      greater risk for thrombotic events and need to be followed-up carefully.

PMID- 8759908
TI  - Denaturing gradient gel electrophoresis: a novel method for determining Rh
      phenotype from genomic DNA.
AB  - Denaturing gradient gel electrophoresis (DGGE) was carried out on PCR products
      amplified from exons 2 and 5 of RHD and RHCE. Exon 2 of RHD and exon 2 of the C
      allele of RHCE have an identical sequence, which differs from that of the c
      allele of RHCE. One band representing D and/or C, and another representing c,
      could be distinguished by DGGE of exon 2 amplifications of genomic DNA from
      individuals with the appropriate Rh phenotype. C and c could only be
      distinguished in D-negative samples. Exon 5 of RHD and exon 5 of the E and e
      alleles of RHCE all have different nucleotide sequences. Bands representing D, E
      and e could be distinguished following DGGE of the products of exon 5
      amplification of genomic DNA from individuals with red cells of the appropriate
      Rh phenotype. In samples from individuals with VS+ red cells (V+ or V-) there was
      a shift of the band representing e. Sequencing demonstrated that VS is associated
      with a RHCE e sequence with a single base change predicting a Leu245 --> Val
      substitution in the Rh polypeptide. This substitution may be responsible for the
      VS and e5 antigens.

PMID- 8759909
TI  - Further improvement of t(8;21) detection by RT-PCR.

PMID- 8759910
TI  - Bone marrow transplantation for Fanconi's anaemia: conditioning with reduced
      doses of cyclophosphamide without radiation.

PMID- 8759911
TI  - Therapy with recombinant erythropoietin in paroxysmal nocturnal haemoglobinuria.

PMID- 8759912
TI  - Protochlorophyllide reduction: a key step in the greening of plants.
AB  - The reduction of Protochlorophyllide (Pchlide) is a major regulatory step in the
      biosynthesis of chlorophyll (Chl) in oxygenic phototrophs. Two different enzymes
      catalyze this reduction: a light-dependent enzyme (LPOR), which is unique as a
      consequences of its direct utilization of light for catalysis; and a light
      independent Pchlide reductase (DPOR). Since the reduction of Pchlide in
      angiosperms is catalyzed exclusively by LPOR, they become etiolated in the
      absence of light. LPOR, a major protein in etioplast membranes, consists of a
      single polypeptide and it exists as a ternary complex with its substrates,
      Pchlide and NADPH. By contrast to the copious information about LPOR, limited
      information about DPOR has been reported. Recent molecular genetic analyses in a
      cyano-bacterium and a green alga have revealed that at least the three genes,
      namely, chlL, chlN and chlB, encode proteins essential for the activity of DPOR.
      These genes are widely distributed among phototrophic organisms with exception of
      angiosperms and Euglenophyta. This distribution seems to be well correlated with
      light-independent greening ability. These genes might have been lost during the
      evolution of gymnosperms to angiosperms. The similarities among the deduced amino
      acid sequences of the three gene products and the subunits of nitrogenase suggest
      an evolutionary relationship between DPOR and nitrogenase. The identification of
      genes for the reduction of Pchlide provides the groundwork for investigations of
      the mechanism that regulates the synthesis of Chl, which is closely coordinated
      with greening in plants.

PMID- 8759913
TI  - The mode of expression and promoter analysis of the arcA gene, an auxin-regulated
      gene in tobacco BY-2 cells.
AB  - The arcA, a member of the G protein beta-subunit family, was isolated from
      tobacco BY-2 cells as an auxin-responsive gene. Characterization of arcA, which
      should help to elucidate the function of the gene product in the plant cells, was
      performed with emphasis on the mode of expression and the analysis of its
      promoter. Accumulation of the arcA message was detected only after treatments
      with auxins and not after treatments with other phytohormones or CdCl2, implying
      that responsiveness of arcA was exclusive to auxin. The putative arcA promoter
      region was fused to a reporter gene for beta-glucuronidase (GUS), and transient
      expression was analyzed in tobacco BY-2 cells. Two series of arcA promoter/GUS
      chimeric genes were constructed. One consisted of a set of 5' nested deletions of
      the arcA promoter connected to the gene for GUS and the other consisted of a
      variety of the arcA promoter fragments fused to a minimal promoter-GUS construct.
      The results indicated that the promoter sequence covering four sets of direct
      repeats (-562 to -167) was necessary for the sufficient response of arcA promoter
      to auxin in BY-2 cells. Moreover, irrespective of auxin treatment, elevated
      activity of GUS driven by this promoter fragment was detected, a result that
      implies that this region behaves an enhancer in BY-2 cells.

PMID- 8759914
TI  - Molecular cloning and characterization of the cDNA for discoidin II of
      Dictyostelium discoideum.
AB  - By using monoclonal antibodies directed against discoidin II, we have isolated
      cDNA clones from axenically grown Ax-2 cells. One cDNA clone (D2) contained a 1.2
      kb insert encoding the entire discoidin II protein, which is composed of 257
      amino acid residues and has a calculated molecular mass of 28,574. The amino acid
      sequences, determined by Edman degradation of six tryptic peptides of discoidin
      II, were identical to those deduced from the cDNA sequence. The protein bears no
      resemblance to any proteins in the data banks, except that its sequence is 49%
      identical with the amino acid sequence of discoidin I. Discoidin II shares with
      discoidin I both a carbohydrate-binding site and an Art-Gly-Asp (RGD) sequence,
      which has been found in fibronectin in mammalian cells. With the onset of
      aggregation (8 h of development), a 1.3-kb discoidin II mRNA begins to
      accumulate. A similar pattern of regulation occurs at the protein level.

PMID- 8759915
TI  - A transcription factor with a leucine-zipper motif involved in light-dependent
      inhibition of expression of the puf operon in the photosynthetic bacterium
      Rhodobacter sphaeroides.
AB  - In the purple nonsulfur photosynthetic bacterium Rhodobacter sphaeroides the
      synthesis of components of the photosystem is regulated in response to oxygen
      tension and light intensity. We have purified and cloned a trans-acting protein
      (SPB) that binds to the promoter region of the puf operon, which encodes the
      apoproteins of light-harvesting complex I and the reaction center. The SPB was
      composed of a single polypeptide with an apparent molecular mass of 15.0 kDa. The
      nucleotide sequence of the spb gene was determined. The gene encoded 104 amino
      acid residues, which correspond to a molecular mass of 11.5 kDa. SPB exhibited
      53% homology to HvrA in Rhodobacter capsulatus. The deduced amino acid sequence
      indicated that SPB contained a region with homology to the leucine-zipper motif
      of c-JUN, a transcription factor in eukaryotes, and SPB also had a DNA-binding
      domain on the amino-terminal side of the leucine-zipper motif. The leucine-zipper
      motif of SPB might contribute to the formation of a dimer. Northern analysis
      indicated that spb was constitutively and monocistronically transcribed in R.
      sphaeroides, irrespective of growth conditions. Structural and functional
      differences between SPB and HvrA are discussed.

PMID- 8759916
TI  - Purification of the cytosolic CuZn-superoxide dismutase (CuZn-SOD) of Marchantia
      paleacea var. diptera and its resemblance to CuZn-SOD from chloroplasts.
AB  - Suspension-cultured cells of Marchantia paleacea var. diptera contain a single
      form of CuZn-superoxide dismutase (SOD; EC 1.15.1.1) which is localized in the
      cytosol. SOD activity was found in cells cultured under heterotrophic,
      photoheterotrophic and photoautotrophic conditions. The CuZn-SOD was purified to
      homogeneity from liverwort cells that had been cultured heterotrophically. Its
      molecular mass was 32.6 kDa, and it contained 17.5 dDa subunits, an indication
      that the enzyme is a homodimer. The enzyme had peaks of absorption at 252, 258
      and 264 nm in the ultraviolet region, due to the presence of phenylalanine, and a
      peak at 680 nm in the visible region, which is characteristic of CuZn-SODs from
      chloroplasts. The amino acid sequence of the amino-terminal region of the enzyme
      exhibited a very high degree of homology to those of chloroplast CuZn-SODs. An
      antiserum raised against the CuZn-SOD from liverwort cross-reacted more strongly
      with the enzyme from spinach chloroplasts, than with the enzyme from spinach
      cytosol. These results indicate that the CuZn-SOD of liverwort resembles CuZn-SOD
      in chloroplasts even though the former is located in the cytosol.

PMID- 8759917
TI  - Submergence enhances expression of a gene encoding 1-aminocyclopropane-1
      carboxylate oxidase in deepwater rice.
AB  - Partial submergence greatly stimulates internodal growth in deep water rice
      (Oryza sativa L.). Previous work has shown that the effect of submergence is, at
      least in part, mediated by ethylene, which accumulates in the air spaces of
      submerged internodes. To investigate the expression of the genes encoding
      ethylene biosynthetic enzymes during accelerated growth of deep water rice, we
      cloned a 1-aminocyclopropane-1-carboxylate (ACC) oxidase cDNA (OS-ACO1) from
      internodes of submerged plants and measured the activity of the enzyme in tissue
      extracts with an improved assay. We found an increase in ACC oxidase mRNA levels
      and enzyme activity after 4 to 24 h of submergence. Thus, it is likely that
      ethylene biosynthesis in internodes of deep water rice is controlled, at least in
      part, at the level of ACC oxidase.

PMID- 8759918
TI  - Occurrence of a novel galactopinitol and its changes with other non-reducing
      sugars during development of Leucaena laucocephala seeds.
AB  - A new cyclitol which is abundant in the late developmental stages of leucaena
      (Leucaena leucocephala (Lam.) de Wit) seeds was identified by HPLC, NMR, and GC
      MS as O-alpha-D-galactopyranosyl-(1-->1)-3-O-methyl-D-chiroinositol, a new
      galactopinitol. This galactopinitol was initially detected midway through seed
      development and increased to 10.2 mg (gDW)-1, but decreased in mature seeds to
      its about a half. Stachyose content increased greatly and remained the most
      abundant of the soluble sugars in mature seeds (25.6 mg (g DW)-1). Artificial
      drying at 73% relative humidity of 70 DPA immature seeds induced the accumulation
      of raffinose, stachyose, galactopinitol and galactinol, but the total amounts of
      these sugars were only about half of those found in mature seeds. Seed
      germination decreased following an initial increase after 8 d artificial drying
      to a moisture content of 24%, and this dehydration damage probably is because of
      underdevelopment of seed tissue. Galactopinitol changes in a similar fashion to
      the oligosaccharides during the late developmental stage and dehydration
      experiment, implying that galactopinitol may play a role in desiccation tolerance
      of leucaena seeds.

PMID- 8759919
TI  - A zinc-finger-type transcription factor WZF-1 that binds to a novel cis-acting
      element of histone gene promoters represses its own promoter.
AB  - WZF-1 is a zinc-finger protein which binds to the wheat histone gene promoter.
      Southwestern-binding analyses revealed that it bound a CACTC sequence, a novel
      positive cis-acting element. The activity of WZF-1 gene promoter, containing six
      CACTC sequences, was markedly reduced when WZF-1 was co-expressed, suggesting
      that WZF-1 is a transcriptional repressor.

PMID- 8759920
TI  - Two novel genes rapidly and transiently activated in suspension-cultured rice
      cells by treatment with N-acetylchitoheptaose, a biotic elicitor for phytoalexin
      production.
AB  - By using subtracted probes, two cDNA clones of rice, EL2 and EL3, were isolated
      as genes responsive within 6 min to N-acetylchitoheptaose, a potent biotic
      elicitor for phytoalexin biosynthesis. Analyses of the sequence of the cDNAs
      showed that both of EL2 and EL3 encoded basic proteins with no significant
      similarities to those of known genes.

PMID- 8759921
TI  - An electrogenic chloride pump in a zoological membrane.
AB  - Two widely documented mechanisms of chloride transport across animal plasma
      membranes are anion-coupled antiport and sodium-coupled symport. No direct
      genetic evidence has yet been provided for primary active chloride transport
      despite numerous reports of cellular CI(-)-stimulated ATPases coexisting, in the
      same tissue, with uphill chloride transport that could not be accounted for by
      the two common chloride transport processes. CI(-)-stimulated ATPases are a
      common property of practically all animal cells, with the major location being of
      mitochondrial origin. It also appears that the plasma membranes of animal cells
      are sites of CI(-)-stimulated ATPase activity. Recent studies of CI(-)-stimulated
      ATPase activity and chloride transport in the same membrane system, including
      liposomes, suggest a mediation by the ATPase in net movement of chloride up its
      electrochemical gradient across animal plasma membranes. Further studies,
      especially from a molecular biological perspective, are required to confirm a
      direct transport role to plasma membrane-localized Cl(-)-stimulated ATPases.

PMID- 8759922
TI  - A Cl- pump in rat brain neurons.
AB  - Cl(-)-stimulated and ethacrynic acid-sensitive ATPase (Cl(-)-ATPase) of plasma
      membrane origin in the rat brain is a candidate for an active outwardly directed
      Cl- translocating system. Biochemistry of Cl(-)-ATPase and ATP-dependent Cl-
      transport (Km values for ATP and Cl-, nucleotide specificity, pH dependency, and
      sensitivity to ethacrynic acid) suggested that Cl(-)-ATPase is an ATP-driven Cl-
      pump. Activity of the reconstituted Cl(-)-ATPase/pump increased in the presence
      of phosphatidylinositol-4-monophosphate, and this pump activity further increased
      at an inside-positive membrane potential or in the presence of a protonophore,
      suggesting that the Cl(-)-ATPase/pump is an electrogenic Cl- transporter,
      probably regulated by phosphoinositide turnover in vivo. In cultured hippocampal
      pyramidal cell-like neurons from embryonic rat brain, ethacrynic acid and ATP
      consuming treatment increased, but furosemide, an inhibitor of Na+/K+/Cl-
      cotransporter, decreased, [Cl-]i when monitored using Cl(-)-sensitive fluorescent
      probes. The stationary levels of [Cl-]i were lower and the effects of ethacrynic
      acid were more prominent in perikarya than in dendrites, while the effects of
      furosemide were more obvious in dendrites than in perikarya. The lower
      perikaryonic [Cl-]i and the marked effects of ethacrynic acid were observed in
      the later stage rather than in the early stage of culture. Thus, region-specific
      localization and developmental changes in the activities of Cl- transporters
      probably result in uneven and age-dependent distribution of Cl- in the neurons.

PMID- 8759923
TI  - Antiport-driven sulfate secretion in an invertebrate epithelium.
AB  - A novel invertebrate gastrointestinal transport mechanism has been shown to
      couple chloride/sulfate exchange in an electrogenic fashion. In the lobster,
      Homarus americanus, the hepatopancreas, or digestive gland, exists as an
      outpocketing of the digestive tract, representing a single cell layer separating
      the gut lumen and an open circulatory system comprised of hemolymph.
      Investigations utilizing independently prepared brush-border and basolateral
      membrane vesicles revealed discrete antiport systems which possess the capacity
      to bring about a transcellular secretion of sulfate. The luminal antiport system
      functions as a high affinity, one-to-one chloride-sulfate exchanger that is
      stimulated by an increase in luminal hydrogen ion concentration. Such a system
      would take advantage of the high chloride concentration of ingested seawater, as
      well as the high proton concentrations generated during digestion, which further
      suggests a potential regulation by resident sodium-proton exchangers. Exchange of
      one chloride for one divalent sulfate ion provides the driving force for
      electrogenic vectorial translocation. The basolateral antiport system was found
      to be electroneutral in nature, responsive to gradients of the dicarboxylic anion
      oxalate, while lacking in proton stimulation. No evidence of sodium-sulfate
      cotransport, commonly reported for the brush border of vertebrate renal and
      intestinal epithelia, was observed in either membrane preparation. The two
      antiporters together can account for the low hemolymph to seawater sulfate levels
      previously described in decapod crustaceans. A secretory pathway for sulfate
      based upon electrogenic chloride-antiport may appear among invertebrates partly
      in response to digestion taking place in a seawater environment.

PMID- 8759924
TI  - Voltage-dependent chloride channels: invertebrates to man.
AB  - Chloride channels are ubiquitous proteins found in invetebrates to man. Cl- is
      one of the most abundant biological anions and accounts for a measurable fraction
      of the electrical conductance of many biological membranes. Physiologically this
      contributes to cellular processes, including pH regulation, volume regulation,
      generation of the resting membrane potential, and regulation of membrane
      excitability. The unitary conductance of voltage-dependent Cl- channels is as
      diverse as the number of different types of Cl- channels described ranging from 5
      450 pS. Cl- channels are highly anion selective passing at least ten anionic
      species, including all of the halides. Cl- channels are blocked by various
      agents, including aromatic acids, inorganic cations, and protons. Maintaining
      high resting conductance and normal excitability, regulating cell volume, and
      modulating hormone action are some examples of the functions of Cl- channels.
      Despite the large amount of data accumulated on voltage-dependent Cl- channels,
      identifying subsets within this class of channels with coherent biophysical
      features that subserve each specific function is still not possible. At present,
      the molecular structure for every type of functional Cl- channels has not been
      determined, but future identification of cloned Cl- channel structures should
      provide a clearer understanding of the functional properties of background Cl-
      channels.

PMID- 8759925
TI  - Regulation of the CFTR chloride channel from humans and sharks.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) in an ATP
      dependent channel which mediates cAMP-stimulated chloride secretion by epithelia,
      particularly those of the pancreas, airways, and intestine. CFTR homologues have
      been found in all higher vertebrates examined to date and also in some lower
      vertebrates, although only the human, shark, and Xenopus genes have been
      heterologously expressed and shown to generate protein kinase A-activated Cl
      channels. Once phosphorylated, CFTR channels require hydrolyzable nucleotides to
      be active, but they can be locked in an open burst state when exposed to mixtures
      of ATP and its hydrolysis-resistant analogue AMP-PNP. This locking requires low
      level phosphorylation at unidentified sites that are not among the ten "strong"
      (dibasic) PKA consensus sequences on CFTR. Mutagenesis of the dibasic PKA sites,
      which reduces in vitro phosphorylation by > 98%, reduces open probability (Po) by
      about 50% whilst having no effect on burst duration. Thus, incremental
      phosphorylation of these sites under normal conditions does not increase Po by
      slowing down ATP hydrolysis and stabilizing the open burst state, although
      locking does strictly require low-level phosphorylation at one or more cryptic
      sites. In addition to serving as a Cl channel, there is compelling evidence that
      CFTR inhibits the amiloride-sensitive, epithelial sodium channel (ENaC). The
      mechanism of coupling is not known but most likely involves physical interactions
      between the channels, perhaps mediated by an intermediate protein that impinges
      on other transport proteins. CFTR does not function as a conductive channel for
      ATP; however, extracellular ATP does regulate epithelial channels through
      activation of P2U purinergic receptors and, after being hydrolyzed
      extracellularly, through activation of adenosine receptors which elevate cAMP.

PMID- 8759926
TI  - Nature and control of chloride transport in insect absorptive epithelia.
AB  - Insect epithelia most commonly absorb from KCI-rich, low Na+ fluids. This is true
      of the locust hindgut, which is functionally analogous to vertebrate kidney
      tubules. Active absorption of Cl- at the apical membrane is the predominant
      transport process giving rise to a large short-circuit current (Isc) after
      stimulation by neuropeptides (CTSH, ITP) via cAMP as second messenger. This Cl-
      transport is not coupled to or driven secondarily by Na+, K+, HCO3-, Ca2+, or
      Mg2+ movements. An apical V-type H+ ATPase acidifies the hindgut lumen but at a
      rate that is 10-15% of Cl-dependent Isc. The evidence to date as to whether the
      resulting large apical proton gradient is used to drive Cl- transport secondarily
      by an apical H+/Cl- symport is mixed. Thus a primary mechanism of Cl- absorption
      remains an alternative possibility. The complete primary structure of a large
      neuropeptide stimulant (ITP: 72 amino acids) of locust ileal Cl- transport has
      recently been deduced from its cDNA. This is the first putative insect
      neuropeptide hormone shown to stimulate ion transport across absorptive epithelia
      for which the primary sequence has been deduced.

PMID- 8759927
TI  - Incorporation of bromodeoxyuridine in regenerating fin tissue of the goldfish
      Carassius auratus.
AB  - We have investigated the pattern of incorporation of 5-bromo-2'-deoxyuridine-5'
      monophosphate (BrdU) by proliferating cells during regeneration of the tail fin
      of Carassius auratus. Fifteen days after amputation, intraperitoneal injection of
      a single dose of 0.25 mg/g wet weight of BrdU and subsequent immunocytochemical
      detection on sections revealed groups of replicating cells in the blastema and
      epidermis at different proximodistal levels. Proliferating blastemal cells were
      confined to a crowded, compact distal area that lost its replicative capacity
      laterally, causing the differentiation of scleroblasts, which synthesize the
      lepidotrichia hemisegments. Proximally, but centrally located, the blastemal
      cells did not incorporate BrdU and they differentiated giving rise to the mature
      intraray connective tissue. An independent cell-proliferation process was noted
      in the epidermis. The distal cap did not proliferate; the lateral faces of the
      epidermis showed high rates of cell replication in the central layer at every
      level of the regenerate rays; quiescent cells remained in the superficial layers.
      The basal epidermal cells did not incorporate BrdU when actinotrichia were
      present. The possible role of basal epidermal cells in the synthesis of
      actinotrichia, the contribution of these collagen macrofibrils to the
      morphogenetic process, and the different pathways of cell differentiation during
      fin regeneration are discussed.

PMID- 8759929
TI  - n-3 fatty acids and cell-cell interaction.

PMID- 8759930
TI  - Association of fibrinogen-bound glycoprotein IIb-IIIa complexes on the activated
      platelet surface.

PMID- 8759931
TI  - Zinc modulation of immune function: specificity and mechanism of interaction.

PMID- 8759932
TI  - Academic medicine: building on the strengths of the past as we approach a cloudy
      future.

PMID- 8759933
TI  - Store-operated Ca2+ influx: what is the message from the stores to the membrane?

PMID- 8759934
TI  - Inhibition of phagocyte-endothelium interactions by oxidized fatty acids: a
      natural anti-inflammatory mechanism?
AB  - Diets rich in marine fish oil may protect against cardiovascular disease.
      Although the mechanisms involved in such protection are not known, fish oils have
      been reported to exert anti-inflammatory actions. For example, dietary fish oil
      supplementation was observed to profoundly decrease the numbers of monocytic
      cells adherent to endothelium overlying atherosclerotic lesions in pigs. We have
      therefore investigated the possibility that fish oil components-particularly n-3
      polyunsaturated fatty acids (PUFAs)-might inhibit phagocyte-endothelium
      interactions. We have found that binding of a monocytic cell line (U937) to
      cultured endothelium (with cell adhesion molecules up-regulated by exposure to
      lipopolysaccharide (LPS), interleukin-1 alpha, tumor necrosis factor-alpha, or
      phorbol myristate acetate (PMA) is greatly decreased by pre-exposure of
      endothelial cells to n-3 and other PUFAs that are incidentally or purposefully
      oxidized; unoxidized PUFAs are completely ineffective. Decreased monocyte
      adherence probably derives from diminished up-regulation of endothelial cell
      adherence molecules VCAM-1 and ELAM-1. Oxidized n-3 PUFAs prevent LPS- or PMA
      induced activation of transcription factor NF-kappa B and the consequent
      induction of mRNA for both cell adhesion molecules. Hydroperoxy fatty acids are
      the active principle in oxidized PUFAs because the activity (1) is predominantly
      organic soluble, (2) is obliterated by pretreatment of oxidized material with
      chemical reducing agents, and (3) is diminished by enzymatic reduction of organic
      hydroperoxides with glutathione/glutathione peroxidase. We speculate that this
      suppression of phagocyte-endothelium interactions by oxidized PUFAs may help
      explain the anti-inflammatory and possible anti-atherogenic effects of diets rich
      in fish oil. Perhaps more importantly, this modulation of endothelial cell
      adhesion molecule expression by oxidized lipids may represent a natural mechanism
      whereby inflammation-mediated oxidation of endothelial PUFAs may retard ingress
      of phagocytes and thereby prevent unrestrained phlogistic responses.

PMID- 8759935
TI  - Self-association of bound fibrinogen on platelet surfaces.
AB  - Binding of fibrinogen to receptors on the surfaces of activated platelets
      triggers movement of the ligand-bound receptors. In this study this process was
      followed by using native and colloidal gold-labeled fibrinogen. Both labeled and
      unlabeled proteins on platelet surfaces could be visualized by low-voltage, high
      resolution scanning electron microscopy. Fibrinogen and gold-conjugated
      fibrinogen were observed to bind to platelet surfaces and to trigger identical
      patterns of receptor-ligand complex redistribution. In addition to previously
      described long- and short-range translocation patterns, fibrinogen, either
      unlabeled or conjugated to gold particles, formed small, specific, nonfibrillar
      aggregates after binding to platelet surface receptors. Similar triggering and
      movement resulted from binding of gold-conjugated antibody to the fibrinogen
      receptor, but no subsequent self-association of the antibody-gold was observed.

PMID- 8759936
TI  - Zinc deficiency affects cell cycle and deoxythymidine kinase gene expression in
      HUT-78 cells.
AB  - Although zinc is known to be involved in cell proliferation and DNA synthesis,
      the mechanism by which zinc may regulate these processes is not understood. We
      have studied the role of zinc on cell proliferation and gene expression of a DNA
      synthesizing enzyme, deoxythymidine kinase (TK), in a T helper human malignant
      lymphoblastoid cell line (HUT-78). In zinc-deficient and zinc-sufficient media,
      the cell doubling time (mean +/- SD) of HUT-78 was 59 +/- 8 hours and 32.6 +/- 6
      hours, respectively. The effect of zinc was T cell specific, inasmuch as the cell
      growth of another T malignant lymphoblastoid cell line, MOLT-3 (immature T
      cells), was not affected by zinc deficiency. Iron, copper, or manganese did not
      completely correct the cell growth of zinc-deficient HUT-78 cells. TK activity
      and the relative accumulation of TK-mRNA were significantly decreased in zinc
      deficient cells during the G1 phase of cell cycle in comparison with zinc
      sufficient cells. Nuclear run-on experiments and actinomycin-D studies showed
      that the transcription of TK-mRNA was affected adversely by zinc deficiency. Cell
      cycle studies showed that more zinc-deficient cells remained in S phase and did
      not undergo mitosis in comparison with zinc-sufficient cells. In conclusion, our
      data show that zinc is a T cell-specific growth factor and that a decreased gene
      expression of DNA-synthesizing enzyme TK in zinc-deficient HUT-78 cells in G1
      phase affected adversely the DNA synthesis in S phase and delayed cell cycle.

PMID- 8759937
TI  - Mechanism and computer simulation of immune complex formation, opsonization, and
      clearance.
AB  - A computer simulation of immune complex formation, opsonization, and clearance
      has been developed (ICMODEL) that uses equations describing the kinetics of known
      immunologic processes and an additional pathologic process of immune complex
      mediated tissue damage and antigen production. ICMODEL was used to (1) compare
      simulated with reported immune response kinetics, (2) evaluate the relative
      stability of the immune system described by the simulation, and (3) determine the
      conditions required to produce high immune complex levels as found in patients
      with immune complex-mediated disease. ICMODEL simulated primary and secondary
      immune responses as well as short- and long-term immunity. ICMODEL also depicted
      a relatively stable immune response system. Under certain conditions, however,
      the system could be perturbed, resulting in an unstable response. For example,
      when the rate constant regulating Fc gamma-mediated phagocytosis was decreased
      and the rate constant regulating immune complex-mediated tissue damage/antigen
      production was increased, immune complex concentrations oscillated with time and
      increased exponentially. These data suggest that ICMODEL can be used to define
      the specific parameters that, when perturbed, will give rise to increased immune
      complex concentrations. As such, this model has direct implications for studies
      of immune complex-mediated disease in human patients.

PMID- 8759939
TI  - Abnormal fibrin structure and inhibition of fibrinolysis in patients with
      multiple myeloma.
AB  - Abnormal clot structures have been reported in patients with multiple myeloma,
      and purified immunoglobulin G (IgG) has been shown to influence fibrin assembly
      in purified systems. Recently fibrin structure has been demonstrated to be a
      major determinant of fibrinolytic rates. This study examined the effects of
      purified polyclonal and monoclonal myeloma IgG on fibrin structure and
      fibrinolysis in plasma clots. Clotting was initiated by the addition of thrombin
      (1.0 NIH units/ml) and calcium (10 mmol/L). Gelation was monitored as a time
      dependent increase in optical density (633 nm). Fibrin fiber size (mu = mass
      length ratio) was measured by scanning the gel from 800 to 400 nm. Two
      preparations of polyclonal IgG and plasma samples from 10 patients with myeloma
      were studied. Both Sandoglobulin (Sandoz Pharmaceuticals Corp.) and Gamimmune
      (Miles Inc., Cutter Biological) decreased final gel turbidity as the IgG
      concentration increased from 0 to 15 mg/ml. Because of its high maltose content,
      Gamimmune produced more-pronounced effects. Over a concentration range of 0 to 15
      mg IgG per milliliter, mu decreased from 1.25 to 0.59 x 10(13) daltons/cm for
      Sandoglobulin and from 1.30 to 0.18 x 10(13) daltons/cm for Gamimmune. Polyclonal
      IgG at 15 mg/ml prolonged clot lysis induced by tissue-type plasminogen activator
      (tPA) from 800 seconds to > 12 hours. Similar effects were noted in myeloma
      clots. mu values in myeloma clots were significantly smaller than mu values in
      comparable normal clots. mu became smaller and lysis times became increasingly
      prolonged as the IgG level increased. High IgG concentrations induce thin fiber
      formation and impair fibrinolysis in plasma gels. These results demonstrate that
      fibrinolysis is inhibited in myeloma clots and that the degree of inhibition is
      correlated with IgG-mediated alterations in fibrin structure. Thin fibrin fibers
      may contribute to thrombotic risk in myeloma.

PMID- 8759938
TI  - Interleukin-2 induces increased platelet-endothelium interactions: a potential
      mechanism of toxicity.
AB  - Cancer immunotherapy with interleukin-2 (IL-2) is limited by side effects that
      may cause organ dysfunction. The role of platelets in the generation of IL-2
      induced organ dysfunction has not been studied, although various studies have
      shown that IL-2 therapy activates both platelets and the vascular endothelium. We
      hypothesized that IL-2 therapy may enhance the thrombogenic response to
      inflammatory stimuli through increased platelet-endothelial interactions and that
      these effects could lead to the development of organ dysfunction. C57BI/6 mice
      were treated with IL-2 intraperitoneally for 2 hours (short term) or 2 to 5 days
      (long term) and prepared for in vivo microscopy of the ear microcirculation. Mice
      were injected intra-arterially with fluorescein isothiocyanate conjugated to
      bovine serum albumin (FITC-BSA). Blue light activation of the FITC-BSA in ear
      arterioles induced thrombus formation. The time to initial thrombus formation was
      measured as an index of thrombogenicity. Platelet function was analyzed by
      aggregometry and platelet expression of IL-2 receptors, and the adhesion molecule
      lymphocyte function-associated antigen-1 (LFA-1) was analyzed by flow cytometry.
      Organ dysfunction was evaluated by serum markers. The administration of both
      short-term and long-term IL-2 reduced the time to initial thrombus formation as
      compared with controls. In vitro platelet aggregometry revealed no acute
      alterations in platelet function; however, long-term IL-2 treatment resulted in
      decreased disaggregation rates. There were no platelet IL-2 receptors present,
      and the expression of the adhesion molecule LFA-1 was not altered by IL-2.
      Increased thrombogenicity occurred before the generation of organ dysfunction.
      These data suggest that increased platelet adherence induced by IL-2 is caused by
      effects on the endothelium that could result in microvascular thrombus formation
      and contribute to organ dysfunction.

PMID- 8759940
TI  - Renal function reserve and sodium sensitivity in essential hypertension.
AB  - It has been postulated that glomerular capillary pressure is elevated in sodium
      sensitive types of hypertension. In addition, the presence or absence of renal
      function reserve, in response to a chronic protein load, is thought to be useful
      in predicting the existence of glomerular hypertension. Intrarenal hemodynamic
      parameters in the sodium-sensitive type of essential hypertension were therefore
      calculated by analyzing the pressure-natriuresis curve, and the preservation of
      renal function reserve was evaluated. Fifteen patients with essential
      hypertension were maintained on a normal sodium diet for 1 week and a low-sodium
      diet for a second week in study 1. This protocol was repeated for low and high
      protein intake in 8 patients in study 2. Subjects in study 1 whose mean arterial
      pressure was reduced by more than 10% by sodium restriction were considered
      sodium sensitive (n = 7), with the remaining patients classified as non-sodium
      sensitive (n = 8). There were no significant differences in mean arterial
      pressure (125 +/- 2 mm Hg), glomerular filtration rate (80 +/- 3 ml/min), or
      renal plasma flow rate (355 +/- 24 ml/min) on the normal sodium diet between
      sodium-sensitive and non-sodium-sensitive patients. Glomerular capillary pressure
      (59 +/- 2 mm Hg vs 47 +/- 1 mm Hg, p < 0.0002) was estimated to be elevated in
      sodium-sensitive patients relative to that in non-sodium-sensitive patients,
      whereas the whole kidney ultrafiltration coefficient of glomerular capillary
      walls (0.068 +/- 0.009 (ml/sec)/mm Hg vs 0.221 +/- 0.042 (ml/sec)/mm Hg, p <
      0.005) was decreased. Chronic protein loading increased both glomerular
      filtration and renal plasma flow rates in study 2. Although the sodium
      sensitivity of blood pressure showed no significant correlation with the increase
      in either glomerular filtration or renal plasma flow rate, it showed a weak
      negative correlation with the increase in filtration fraction (r = -0.69, p <
      0.06), which is the ratio of the two rates. Taken together, these results suggest
      that glomerular capillary pressure is elevated and renal function reserve is
      impaired in patients with sodium-sensitive essential hypertension.

PMID- 8759941
TI  - Serum samples from pancreatectomized patients contain trypsinogen
      immunoreactivity.
AB  - The concentrations of trypsinogen-1 and -2 in serum samples from patients who
      have undergone pancreatectomy were measured by highly sensitive and specific time
      resolved immunofluorometric assays. The isoenzyme pattern was determined by ion
      exchange chromatography and determination of immunoreactivity in the fractions.
      All samples contained trypsinogen-2, the mean level being one fifth of that in
      healthy controls. Trypsinogen-1 was detected in one of nine samples. In addition
      to the main trypsinogen isoenzymes, we observed in normal serum two trypsinogen
      isoenzymes previously found in mucinous ovarian cyst fluid. Our results suggest
      that trypsinogen is not exclusively expressed by the pancreas and certain tumors
      but that it also may be produced by normal extrapancreatic tissues. This should
      be considered when an assay of trypsinogen in serum is used for clinical
      purposes.

PMID- 8759943
TI  - Associated daily biosynthesis of cortisol and thromboxane A2: a preliminary
      report.
AB  - Cortisol is the most important hormone secreted in response to acute and chronic
      stress. Thromboxane A2 (TxA2) is a potent eicosanoid with vasoconstricting and
      proaggregatory actions. Our earlier finding of a close correlation between plasma
      levels of TxB2, the stable metabolite of TxA2, and cortisol in subjects with
      major depression but without frank hypercortisolism prompted us to investigate a
      possible association between TxA2 and cortisol production in nondepressed
      subjects. The 24-hour urinary excretion values of 2,3-dinor-TxB2 (the urinary
      catabolite of TxA2) and cortisol were measured by radioimmunoassay in 50 subjects
      divided into three groups matched for age, sex distribution, and body mass index.
      Group 1 consisted of 19 healthy subjects; group 2 consisted of 15 patients with
      type IIa hypercholesterolemia, a condition associated with a high
      atherothrombotic risk, but without history of atherosclerosis or evidence of this
      disorder documented clinically or in noninvasive diagnostic tests; and group 3
      consisted of 16 patients with regional atherosclerosis (8 with cerebrovascular
      disease, 6 with coronary artery disease, and 2 with peripheral vascular disease).
      Although the three groups had similar cortisol and 2,3-dinor-TxB2 urinary values,
      a significant direct correlation emerged between the two catabolites in the whole
      study sample (r = 0.63; p < 0.0001) and the three groups (r1 = 0.62, p < 0.01; r2
      = 0.78, p < 0.0001; r3 = 0.63, p < 0.01). The close association between cortisol
      and thromboxane A2 biosynthesis thus appears to be a general phenomenon. These
      findings may be important in interpreting the well-described causative link
      between stress and atherothrombotic cardiovascular disease.

PMID- 8759944
TI  - Acoustic radiation pressure in a three-dimensional lossy medium.
AB  - Acoustic radiation pressure exerted by an arbitrary acoustic wave in a three
      dimensional lossy medium is calculated by extending an indirect approach
      developed by Chu and Apfel [B-T. Chu and R.E. Apfel, "Acoustic radiation pressure
      produced by a beam of sound," J. Acoust. Soc. Am. 72, 1673-1687 (1982)]. Without
      appealing to the detailed solutions of equations governing fluid motion, a
      general analytic expression for the radiation pressure in lossy media with
      arbitrary waves is obtained. When an infinite lossy medium is considered, the
      expression states that the radiation pressure, to the lowest order of
      approximation (i.e., second order), is equal to corresponding total energy
      density. For a special class of confined spaces, the expression leads to a rather
      general formula for the radiation pressure, in which the radiation pressure is
      given in terms of various energy densities in the field. Furthermore, a
      relationship among these energy densities is generalized to the case of lossy
      media, which enables one to compute the radiation pressure in the class of spaces
      with the knowledge of the first-order perturbation solution only.

PMID- 8759942
TI  - Soluble (1-->3)-beta-D-glucan purified from Candida albicans: biologic effects
      and distribution in blood and organs in rabbits.
AB  - (1-->3)-beta-D-glucan is a ubiquitous constituent of fungi, and elevated plasma
      glucan levels are commonly present in patients with deep mycosis or fungemia. The
      pharmacokinetics, biologic effects, and distribution in blood and organs of
      iodine 125-labeled (1--> 3)-beta-D-glucan purified from Candida albicans
      organisms were analyzed in rabbits during the 24-hour period after intravenous
      administration of this constituent. The intravascular half-life of beta-glucan
      was 1.8 minutes in the low-dose group (9.3 micrograms/kg, n = 3) and 1.4 minutes
      in the high-dose group (222 micrograms/kg, n = 3), and the total body clearance
      was 1.12 +/- 0.30 ml/min and 1.17 +/- 0.16 ml/min (mean +/- SD), respectively
      (not significantly different). The serum concentration of (1-->3)-beta-D-glucan
      was also biologically determined by a test using coagulation factor G of the
      Japanese horse-shoe crab (G test). There was good correlation between the
      clearance of beta-glucan measured biologically and isotopically. During the 24
      hour period of observation the rabbits remained well and beta-glucan failed to
      alter blood cell counts, tumor necrosis factor levels, or lipid metabolism. 125I
      labeled beta-glucan associated with the blood cellular compartment initially was
      less than 3% (the majority in the platelets) and decreased further during the
      following 2-hour period. Over 97% of circulating 125I-labeled beta-glucan was
      associated with the cell-free plasma, and the majority of this glucan in plasma
      appeared not to be associated with lipoproteins. The liver contained more than
      80% of the 125I-labeled beta-glucan detected in the six major organs analyzed.

PMID- 8759945
TI  - Simulation of fixed microphone arrays for directional hearing aids.
AB  - Microphone arrays with fixed optimum weights are known to suppress the background
      noise and reverberation that severely reduce the effectiveness of conventional
      hearing aids. By means of a general technique for digital frequency-domain
      implementation of optimum broadband arrays that was developed recently [C. Liu
      and S. Sideman, J. Acoust. Soc. Am. 98, 241-247 (1995)], a practically promising
      system is proposed to realize the arrays with the well-known sensitivity
      constrained superdirective beamforming weights, and with five identical
      omnidirectional, cardioid, hypercardioid, or dipole microphones, respectively, in
      the endfire or broadside configurations, which were theoretically proposed by
      Stadler and Rabinowitz [J. Acoust. Soc. Am. 94, 1332-1342 (1993)]. The digital
      broadband frequency-domain beamforming system allows the broadband superdirective
      beamforming weights to be faithfully and independently applied to each frequency
      component of the signal. The practical application of this technique is
      demonstrated through computer simulation of the system in anechoic situations.
      Furthermore, its performance in simulated reverberant environments is evaluated.

PMID- 8759946
TI  - On the incorporation of moire shape measurements in finite-element models of the
      cat eardrum.
AB  - The mechanical behavior of the eardrum has previously been shown to depend
      critically on its shape, but accurate shape measurements have been difficult to
      make. Phase-shift moire topography provides a valuable technique for measuring
      such shapes, and measurement in the presence of large static pressures
      facilitates the determination of the boundaries of the pars tensa, pars flaccida,
      and manubrium. New measurements of the shape of the cat eardrum are presented.
      The presence of hysteresis in the pressure-displacement response is demonstrated.
      The shapes are incorporated in individualized finite-element models for four
      different ears, and the variability between and within animals is examined. Fixed
      manubrium low-frequency displacements are simulated and compared for the
      different models.

PMID- 8759947
TI  - Finite-element modeling of the normal and surgically repaired cat middle ear.
AB  - In this work, three-dimensional finite-element models of the normal and
      surgically repaired cat middle ear were developed. The normal middle-ear model
      was formed by adding explicit representations for the footplate and cochlear load
      to an existing model of the cat eardrum. The footplate was modeled as a thin
      plate with a thickened rim. The cochlear load was represented by springs attached
      along the footplate's periphery. The model is valid for frequencies below 1 kHz
      and for physiological sound levels. Eardrum and manubrium displacement, and out
      of-plane displacements of the footplate's center, were found to compare well with
      experimental results. The normal model was modified to simulate the effects of
      two types of middle-ear surgery, both of which are used to repair a discontinuous
      ossicular chain. Bulging of the footplate was found to occur when a prosthesis
      made direct contact with the footplate. The location of the prosthesis along the
      manubrium did not affect the motion of the footplate as long as the joints were
      all rigid. When the joints were flexible, the largest displacements occurred when
      the prosthesis was positioned near the upper end of the manubrium.

PMID- 8759948
TI  - Distortion product otoacoustic emissions created through the interaction of
      spontaneous otoacoustic emissions and externally generated tones.
AB  - Spontaneous otoacoustic emissions (SOAEs) and external tones (XTs) were used as
      primaries f2 and f1, respectively (frequency of f2 > f1) to create 2f1--f2
      distortion product otoacoustic emissions (DPOAEs). Amplitude and frequency of the
      SOAEs, XTs, and DPOAEs were recorded by placing a sensitive microphone in the ear
      canal and extracted using fast Fourier transform analysis. XTs were presented to
      ten ears at SOAE/f1 ratios between 1.08 and 1.22. XTs were incremented in 5-dB
      steps and ranged from levels equal to the initial SOAE amplitudes to levels at
      which the SOAEs and DPOAEs were suppressed into the noise floor. Results
      indicated that DPOAE amplitudes and SOAE suppression characteristics were
      idiosyncratic. Despite the variability, the following trends were noted: (1) at
      larger frequency ratios, DPOAE generation and SOAE suppression were associated
      with greater XT levels; (2) DPOAE growth functions were characterized by slopes
      less than 1 dB/dB, a maximum, rollover and disappearance into the noise floor
      with increasing XT levels; (3) maximum amplitude DPOAEs were observed at
      frequencies approximately one-half octave lower than the SOAE (f2); (4) the
      presence of DPOAEs was associated with SOAE suppression; (5) the most common SOAE
      frequency shift, in the presence of XT stimulation, was a shift to a higher
      frequency.

PMID- 8759949
TI  - Toward optimizing the clinical utility of distortion product otoacoustic emission
      measurements.
AB  - This study examined the effect of primary stimulus level on the ability of
      distortion product otoacoustic emission (DPOAE) measurements to separate normal
      hearing from hearing-impaired ears. Complete I/O functions were obtained for nine
      f2 frequencies on 210 people approximately evenly divided between normal hearing
      and hearing impaired. Clinical decision theory was used to assess both DPOAE
      amplitudes and DPOAE threshold as diagnostic indicators of hearing status.
      Moderate level primary stimuli elicited responses that separated normal from
      impaired better than either lower level or higher level stimuli. The two
      populations were differentiated for all frequencies above 500 Hz by DPOAE
      amplitude, given primary levels, L1 and L2, of 65 and 55 dB SPL. DPOAE threshold
      performed equally well, but threshold ambiguity in noise and longer testing times
      make it a less suitable DPOAE measure to use diagnostically.

PMID- 8759950
TI  - The use of cumulative distributions to determine critical values and levels of
      confidence for clinical distortion product otoacoustic emission measurements.
AB  - Distortion product otoacoustic emission (DPOAE) input/output functions were
      measured at nine f2 frequencies ranging from 500 to 8000 Hz in 210 normal-hearing
      and hearing-impaired subjects. In a companion paper [Stover et al., J. Acoust.
      Soc. Am. 100, 956-967 (1996)], L1-L2 was held constant at 10 dB, and L2 was
      varied from 65 to 10 dB SPL in 5-dB steps. Based upon analyses using clinical
      decision theory, it was demonstrated that DPOAE amplitudes for 65/55 dB SPL
      primaries (L1/L2) and DPOAE thresholds resulted in the greatest separation
      between normal and impaired ears. In this paper, the data for these two
      conditions were recast as cumulative distributions, which not only describe the
      extent of overlap between normal and impaired distributions, but also provide the
      measured value (i.e., the specific DPOAE amplitude or threshold) for any
      combination of hit and false alarm rates. From these distributions, confidence
      limits were constructed for both DPOAE amplitude and threshold to determine the
      degree of certainty with which any measured response could be assigned to either
      the normal or impaired population. For these analyses, DPOAE measurements were
      divided into three categories (a) response properties that would be unlikely to
      come from normal ears, (b) response properties that would be unlikely to come
      from impaired ears, and (c) response properties for which hearing status was
      uncertain. Based upon DPOAE amplitude measurements, the region of uncertainty,
      defined between the 95 percentile for impaired ears and the 5 percentile for
      normal ears, was relatively narrow for f2 frequencies ranging from 707 to 4000
      Hz. For DPOAE thresholds, this region was relatively narrow for F2 frequencies
      ranging from 1414 to 4000 Hz.

PMID- 8759951
TI  - Effects of stimulus rate on the feline brain-stem auditory evoked response during
      development. I. Peak latencies.
AB  - The effects of stimulation rate on the brain-stem auditory evoked response (BAER)
      of developing and adult cats were investigated. Age ranged from 10-post-natal
      days to young adults. Clicks were presented at levels of 90 dB pSPL and 20 dB
      above each animal's click threshold (20 dB SL). For all animals, a conventional
      BAER rate series was obtained at rates of 5, 10, 30, 60, and 90 Hz. BAERs were
      also obtained using pseudorandom pulse sequences called maximum length sequences
      (MLSs). The minimum time between pulses, the minimum pulse interval (MPI),
      included 0.5, 1, 2, 4, and 6 ms, which correspond to average rates of 1000, 500,
      250, 125, and 83 Hz, respectively. Dependent variables included the latencies of
      the first four BAER peaks, labeled i through iv. MLS BAERs were indistinguishable
      from conventional BAERs at all ages studied. In general, for both conventional
      and MLS BAERs, peak latencies and the i-iv interval increased with increasing
      stimulus rate. Although absolute peak latencies and the i-iv interval decreased
      systematically with age, the relative shift in latency and i-iv interval induced
      by increasing stimulus rate decreased during development. The enhanced
      sensitivity to stimulus rate observed at younger ages was not the consequence of
      the threshold improvement that occurs during development since similar
      observations were made when stimuli were presented at a constant absolute level
      (90 dB pSPL) or at a constant level above threshold (20 dB SL). In addition,
      successive BAER peaks exhibited progressively larger latency shifts with
      increasing stimulus rate at all ages studied. These data suggest that higher
      stimulus rates produce greater neural adaptation resulting in prolonged BAER peak
      latencies. Furthermore, the effects of adaptation are cumulative across synapses,
      and the mechanisms responsible for the acquisition of adult-like adaptation
      properties develop during the early post-natal period in the cat.

PMID- 8759952
TI  - Effects of stimulus rate on the feline brain-stem auditory evoked response during
      development. II. Peak amplitudes.
AB  - The effects of click rate on brain-stem auditory evoked response (BAER) peak
      amplitudes were investigated in adult cats and kittens in four age groups: 10,
      15, 20, and 30 post-natal days. Conventional BAERs were obtained at rates of 5,
      10, 30, 60, and 90 Hz. Maximum length sequences (MLSs) were used to obtain
      responses at rates of 83, 125, 250, 500, and 1000 Hz. For both techniques, clicks
      were presented at 90 dB pSPL, and at 20 dB above threshold (20 dB SL). BAERs were
      observed for all age groups, at all click rates. However, not all peaks could be
      identified in all animals, with peak absence more common for the youngest kittens
      at the higher rates. BAER waves i through iv decreased in amplitude with
      increasing click rate for all age groups. In general, the smallest peak
      amplitudes were observed for the youngest animals (10- to 15-day-old) studied,
      while the largest amplitudes were found for the adult, 20- or 30-day-old animals,
      regardless of rate. When amplitudes were normalized to eliminate the influences
      of differences in absolute values due to developmental stage (i.e., made
      proportional to the amplitude observed at 5 Hz), the younger age groups exhibited
      enhanced sensitivity to the effects of stimulus rate. However, exceptions to this
      trend were observed. In general, amplitudes of BAER peaks obtained with the MLS
      procedure were smaller than those obtained using conventional averaging with a
      similar average click rate, regardless of age. Finally, the most efficient method
      for obtaining a response at a criterion signal-to-noise ratio was typically by
      the use of conventional averaging at a rate of 60 or 90 Hz, for all peaks and age
      groups, Overall, these data suggest that higher stimulus rates produce greater
      neural adaptation resulting in reduced BAER peak amplitudes. The mechanism
      responsible for the acquisition of adult-like adaptation properties appears to
      develop during the early post-natal period in the cat.

PMID- 8759953
TI  - The cubic distortion product otoacoustic emissions from the normal and noise
      damaged chinchilla cochlea.
AB  - A normative study of the cubic distortion product emissions from 104 monaural and
      binaural chinchillas was undertaken to establish criteria upon which noise
      exposed animals could be evaluated. From this normative group, 47 randomly
      selected chinchillas were exposed to various high level (150-, 155-, and 160-db
      peak SPL) impulse noises. Auditory evoked potentials and cubic distortion product
      otoacoustic emissions were measured on each animal pre- and post-exposure and
      related to the sensory cell populations 30 days post-exposure. Both group mean
      and individual animal data indicated that the distortion product emissions were
      more sensitive, frequency-specific indices of noise-induced cochlear effects than
      pure-tone threshold measures. This was particularly evident near the threshold
      for noise-induced damage to the outer hair cell system.

PMID- 8759954
TI  - On the relation between comodulation masking release and temporal modulation
      transfer functions.
AB  - Explanations for the phenomenon known as comodulation masking release (CMR)
      generally assume that temporal envelope information from different peripheral
      filters is compared, thus entailing multiple envelope representations. Here it is
      shown that a leaky-integrator model, yielding a single envelop representation
      extracted from a broad frequency range, provides an alternative account of CMR.
      One prediction obtained from model simulations is that adding a single tone to
      the stimulus will disrupt the CMR effect, leading to an increase in thresholds.
      Supporting evidence from several experiments shows that the magnitude of CMR is
      reduced following the addition of a single tone, even when separated from
      comodulated masking and flanking bands by more than an octave. Whereas these
      findings are consistent with the leaky-integrator model, they cannot be easily
      explained by models which assume multiple envelope representations.

PMID- 8759955
TI  - Loudness enhancement and intensity discrimination under forward and backward
      masking.
AB  - There is a large deterioration in intensity discrimination performance at medium
      levels for a 30-ms sinusoidal pedestal presented 100 ms before or 100 ms after an
      intense masker [Plack and Viemeister, J. Acoust. Soc. Am. 92, 3097-3101 (1992)].
      It has also been demonstrated that the loudness of a 30-ms sinusoidal tone burst,
      presented 100 ms after a masking tone burst, is enhanced at mid-levels [Zeng, J.
      Acoust. Soc. Am. 96, 2127-2131 (1994)]. The present experiment measured intensity
      discrimination and loudness enhancement in both forward and backward masking. A
      double-staircase adaptive procedure was used to match the loudness of a 30-ms, 1
      kHz standard sinusoid presented in quiet to the loudness of a 30-ms, 1-kHz
      sinusoid presented 100 ms after (forward masking) or 100 ms before (backward
      masking) a 110-ms, 90-dB, 1-kHz masking sinusoid. The mean of the thresholds from
      the two staircases was used to determine the amount of enhancement, and the
      difference between the thresholds from the two staircases was used to determine
      the intensity just noticeable difference (jnd). Four listeners were tested at a
      range of standard levels between 30 and 90 dB. For all listeners, in both forward
      and backward masking, the jnd and loudness were greatest at mid-levels (40-70
      dB). For a given listener, there was no substantial difference between the form
      of the results under forward and compared to backward masking, although there was
      considerable variability in the size of the effects between the individual
      listeners. Combining all the data, for both forward and backward masking there
      was a positive correlation between the size of the jnd and the magnitude of the
      loudness enhancement, although the correlation was only significant in backward
      masking (p < 0.005). Taken with the results of Zeng, these data suggest a link
      between loudness enhancement and the jnd increase, and a link between the
      mechanisms underlying the effects of forward and backward masking on intensity
      discrimination. It is suggested that all these effects may be caused by long-term
      loudness integration in the auditory system.

PMID- 8759956
TI  - Temporal factors in referential intensity coding.
AB  - Three experiments investigated the finding [Plack et al., J. Acoust. Soc. Am. 97,
      1141-1149 (1995)] that intensity discrimination under backward masking can be
      improved by presenting an additional, "proximal," tone burst shortly before or
      after the pedestal. All the stimuli used in the experiments were 30-ms, 1-kHz
      sinusoids. In the first experiment, intensity discrimination was measured for a
      50-dB SPL pedestal presented 100 ms before an 80 dB SPL masker. A proximal tone
      burst was presented either before or after the pedestal, separated from the
      pedestal by a brief silent gap. For the conditions in which the proximal burst
      was before the pedestal, adding a proximal burst with a higher level than the
      pedestal produced an improvement in intensity discrimination. The most effective
      level of the proximal burst increased as the gap was increased. For the
      conditions in which the proximal burst was after the pedestal, two listeners
      showed an improvement when the proximal burst was lower in level than the
      pedestal, and one listener showed an improvement when the proximal burst was
      higher in level than the pedestal. In a second experiment, detection threshold
      measurements showed that good performance was not dependent on the proximal burst
      making the pedestal in one of the two observation intervals. The final experiment
      used a selective training procedure to demonstrate that listeners were basing
      performance on two conflicting strategies, namely, to pick the interval that
      sounded as if it had three tone bursts in it when the proximal level was higher
      than the pedestal level, and to pick the interval that sounded as if it had two
      tone bursts in it when the proximal level was lower than the pedestal level. A
      model of temporal resolution is presented that can explain certain aspects of the
      results in terms of the detection of "bumps" in the temporal excitation patterns
      produced by the stimuli. In conditions of backward masking, these relative
      features seem to provide a superior cue for intensity discrimination than
      absolute intensity, which is actively rejected as a cue.

PMID- 8759957
TI  - Development of auditory information integration abilities.
AB  - The ability of normal-hearing children (aged 4 through 7 years) and adults to
      integrate information was measured in an auditory sample discrimination task. On
      each trial a pair of tonal sequences was played whose component frequencies were
      randomly drawn from two equal-variance, Gaussian distributions with different
      means. The listeners task was to identify the sequence drawn from the
      distribution with the higher mean frequency. Performance was first evaluated as a
      function of the number of components in each sequence. Results showed that
      discrimination accuracy improved with increasing age until age 7, at which time
      performance was adult-like. The 7-year-olds and the adults discriminated the
      sequences with increasing accuracy as the sequence length was increased, but the
      4-to 6-year-old listeners, as a group, did not. Data were fitted with a model
      with two free parameters, one representing resolution of the components and
      presumed to reflect peripheral processing, and another representing central noise
      added to the decision process after the component information is combined [R.
      Lutfi, J. Acoust. Soc. Am. 86, 934-944 (1989)]. On average, both parameters
      showed gradual changes as age increased, with adult-like values by 7 years of
      age. Individual data however suggest that the changes in central noise with age
      may be less gradual than the changes in peripheral resolution. In a second
      condition, increases in component duration produced improved performance for the
      7-year-olds and the adults, while that of the younger listeners remained the
      same. Fitted parameters suggested improvements in component resolution for the
      older children, with no changes in central noise levels. In a third condition,
      reducing the overlap in the distributions improved performance for only a few of
      several younger children. This improvement was attributable to lower levels of
      central noise. Overall, these results suggest that with increasing age children
      are better able to discriminate between sounds that are variable and have
      overlapping acoustic characteristics. This age-related improvement may be
      attributed both to improvements in the ability to resolve the components and to
      reductions in central noise.

PMID- 8759958
TI  - Vowel discrimination in cats: thresholds for the detection of second formant
      changes in the vowel /epsilon/.
AB  - The ability of cats to discriminate changes in the second formant of the vowel
      /epsilon/ was examined across a range of stimulus levels. Cats were trained to
      press and hold down a lever to produce a pulsed train of the standard vowel
      /epsilon/, and to release the lever only when a variant of [epsilon] occurred.
      Six synthetic variants of /epsilon/ had the same first and third formants (F1 and
      F3), but with the second formant (F2) located between 1700 and 2000 Hz. All
      stimuli were tested at levels of 10, 30, 50, and 70 dB SPL. Average difference
      thresholds for changes in F2 (delta F2) of the vowel /epsilon/ ranged from 87 to
      36 Hz across levels of 10 to 70 dB SPL, and were only slightly above those of
      humans. Further, the delta F2 values were lower than pure-tone delta F values in
      the same frequency range, whereas humans exhibit higher delta F2 values than pure
      tone delta F values in the same frequency range. Changes in the second formant in
      a negative direction (downward F2 shifts) were also found to be more difficult to
      detect than upward F2 shifts. These results suggest that, compared to pure tones,
      cats are better able to discriminate small changes in more complex, vowel-like
      stimuli.

PMID- 8759959
TI  - Sound orientation behavior in cats. I. Localization of broadband noise.
AB  - Behavioral experiments measured the accuracy of the cat's voluntary head
      orientation responses to bursts of broadband noise at 104 locations in the
      frontal sound field. Cats were presented sound stimuli at randomly selected
      locations and received a food reward for releasing a lever when a light-emitting
      diode (LED) flashed at the same location. Head movements to the perceived
      location of the acoustic stimulus, and therefore expected location of the LED
      cue, were tracked by an electromagnetic sensor. Orientation responses to single
      sound bursts were directed to within 5 degrees of the azimuth and elevation of
      sounds within 15 degrees of the immediate frontal field and did not change for
      burst durations of 40, 100, and 200 ms. An increasing underestimation of target
      location was observed as the sound stimulus moved to more lateral azimuths and
      higher elevations. The "undershoot" phenomenon was reduced by allowing subjects
      to track paired stimulus bursts that repeated from the same location. These
      effects of sound location on the accuracy of orientation responses are predicted
      by the availability of mid-frequency spectral cues for sound localization.

PMID- 8759960
TI  - Sound orientation behavior in cats. II. Mid-frequency spectral cues for sound
      localization.
AB  - The cat's head-related transfer function creates a directionally dependent mid
      frequency notch in the amplitude spectrum of a broadband sound as the stimulus
      propagates to the tympanic membrane [Rice et al., Hear. Res. 58, 132-152 (1992)].
      Our previous behavioral studies [May and Huang, J. Acoust. Soc. Am. 100, 1059
      1069 (1996)] have indicated that the cat's sound-evoked orientation responses are
      well directed to the azimuth and elevation of broadband noise bursts in the
      frontal sound field, where pinna-based spectral notches are prominent and change
      systematically with sound direction. In the present study, the importance of mid
      frequency directional cues in the cat's sound localization behavior was further
      evaluated by manipulating the frequency and bandwidth of orientation stimuli. The
      accurate pattern of orientation behavior seen previously with bursts of broadband
      noise was relatively unaffected when stimulus bandwidth was decreased to mid
      frequency bandpass noise of 5-18 kHz. In contrast, poorly directed head
      orientation responses were observed in tests with high-pass noise (> 18 kHz) and
      mid-frequency pure tones. When tested with narrow bands of mid-frequency noise,
      cats oriented toward the spatial location where HRTF-filtering properties most
      closely matched the stimulus spectrum. These results suggest that important sound
      localization cues are derived from mid-frequency spectral features of the cat's
      HRTF.

PMID- 8759961
TI  - The perception of temporal patterns for electrical stimulation presented at one
      or two intracochlear sites.
AB  - The question of how well the temporal structure in pulsatile electrical
      stimulation is perceived, and the nature of the information that may be conveyed
      by this temporal structure, is of importance to the further development of speech
      processing strategies for cochlear implants. The two experiments described here
      investigated the perception of temporal fine structure in amplitude modulated 1
      kHz pulse trains, both when a single electrode position was used, and when the
      pulses alternated between two electrode positions. Five subjects with the Mini
      System 22 implant took part in these experiments. The amplitude modulations were
      constructed so that all dual-electrode stimuli had the same temporal pattern on
      each individual electrode but differed in the aggregate temporal pattern A
      hypothesis was investigated that subjects perceive the aggregate temporal pattern
      rather than the pattern at each individual electrode place, only when the
      electrodes are less than a critical distance apart. The first of these two
      experiments used a four-interval forced-choice task to measure the ability of
      subjects to detect changes in the aggregate temporal pattern. At electrode
      distances greater than 3 to 4 mm, subjects could no longer perceive the aggregate
      pattern, confirming the hypothesis. The second experiment used a single-interval
      pitch estimation task to test the hypothesis that the perceptual differences in
      temporal patterns measured in the previous experiment were classified similarly
      to rate pitch differences by the subjects. The results confirmed this hypothesis,
      and showed that the pitch of the modulated stimuli could be predicted by the
      expected inter-pulse intervals in the excited neural population.

PMID- 8759962
TI  - Speech compensation to structural modifications of the oral cavity.
AB  - Acoustic and perceptual analyses of vowels, stops, and fricatives produced with
      and without an artificial palate were conducted. Recordings were made both
      immediately upon insertion of the palate and following a 15-min adaptation
      period. Results of the acoustic analyses revealed significant alterations in the
      fricative spectra under conditions of perturbation with fewer, if any, changes in
      the vowels and stop consonants. Perceptual data confirmed these patterns and
      provided evidence of possible improvements in compensation over time. The data
      are compared to our previous studies of speech sound articulation under bite
      block conditions. Differences between adaptation to modifications of oral
      structure (artificial palate) and oral function (jaw fixation by a bite block)
      are considered.

PMID- 8759963
TI  - A comparison of speech envelopes of stutters and nonstutterers.
AB  - A new parameter, the area under the speech envelop, was used to evaluate the
      degree of speech dysfluency in stutterers. This parameter has been measured for
      100-s utterances of 30 fluent speakers and 30 stutterers speaking with
      simultaneous auditory feedback (SAF) and delayed auditory feedback (DAF). A
      correlation was found between the area under the speech envelope and the severity
      of stuttering. Thus for stutterers, this parameter can be used to evaluate the
      degree of the disturbance of fluency. The values of this parameter were
      significantly higher in fluent utterances than in nonfluent ones. The reduction
      of stuttering observed in stutterers under DAF was accompanied by an increase of
      the area under the speech envelope, making it comparable to the one measured for
      the utterances of fluent speakers.

PMID- 8759964
TI  - The perceptual magnet effect as an emergent property of neural map formation.
AB  - The perceptual magnet effect is one of the earliest known language-specific
      phenomena arising in infant speech development. The effect is characterized by a
      warping of perceptual space near phonemic category centers. Previous explanations
      have been formulated within the theoretical framework of cognitive psychology.
      The model proposed in this paper builds on research from both psychology and
      neuroscience in working toward a more complete account of the effect. The model
      embodies two principal hypotheses supported by considerable experimental and
      theoretical research from the neuroscience literature: (1) sensory experience
      guides language-specific development of an auditory neural map, and (2) a
      population vector can predict psychological phenomena based on map cell
      activities. These hypotheses are realized in a self-organizing neural network
      model. The magnet effect arises in the model from language-specific
      nonuniformities in the distribution of map cell firing preferences. Numerical
      simulations verify that the model captures the known general characteristics of
      the magnet effect and provides accurate fits to specific psychophysical data.

PMID- 8759965
TI  - Prominence lent by rising and falling pitch movements: Testing two models.
AB  - Two experiments are reported in which a pitch-level difference (PLD) model for
      prominence perception [Hermes and Rump, J. Acoust. Soc. Am. 96, 83-92 (1994)] is
      subjected to further tests. The model holds that the contribution of pitch to the
      perceived degree of prominence is proportional to the difference in pitch level
      between the vocalic nuclei of the accented and the previous syllable. In
      experiment I, the influence of stretching and compressing the utterance in time
      was assessed. It was found that the predictions made by the model were not fully
      supported by the data. An alternative model was developed according to which
      pitch movements resynthesized in the same register lend equal prominence when
      pitch levels on the upper declination lines in the stimuli are equal. These two
      models gave different predictions when the lower declination lines are different.
      This was tested in experiment II. The results which are more or less between the
      predictions by the two models suggest that low pitch levels play a smaller role
      in prominence perception than high pitch levels do.

PMID- 8759966
TI  - Speech versus nonspeech in pitch memory.
AB  - The memory trace of the pitch sensation induced by a standard tone (S) can be
      strongly degraded by subsequently intervening sounds (I). Deutsch [Science 168,
      1604-1605 (1970)] suggested that the degradation is much weaker when the I sounds
      are words than when they are tones. In Deutsch's study, however, the pitch
      relations between S and the I words were not controlled. The first experiment
      reported here was similar to that of Deutsch except that the speech and nonspeech
      stimuli used as I sounds were matched in pitch. The speech stimuli were
      monosyllabic words derived from recordings of a real voice, whereas the nonspeech
      stimuli were harmonic complex tones with a flat spectral profile. These two kinds
      of I sound were presented at a variable pitch distance (delta-pitch) from the S
      tone. In a same/different paradigm, S had to be compared with a tone presented 6
      s later; this comparison tone could be either identical to S or shifted in pitch
      by +/- 75 cents. The nature of the I sounds (spoken words versus tones) affected
      discrimination performance, but markedly less than did delta-pitch. Performance
      was better when delta-pitch was large than when it was small, for the speech as
      well as nonspeech I sounds. In a second experiment, the S sounds and comparison
      sounds were spoken words instead of tones. The differences to be detected were
      restricted to shifts in fundamental frequency (and thus pitch), the other
      acoustic attributes of the words being left unchanged. Again, discrimination
      performance was positively related to delta-pitch. This time, the nature of the I
      sounds (words versus tones) had no significant effect. Overall, the results
      suggest that, in auditory short-term memory, the pitch of speech sounds is not
      stored differently from the pitch of nonspeech sounds.

PMID- 8759967
TI  - Modeling the perception of concurrent vowels: Role of formant transitions.
AB  - When two synthetic vowels are presented concurrently and monaurally, listeners
      identify the members of the pair more accurately if they differ in fundamental
      frequency (F0), or if one of them is preceded or followed by formant transitions
      that specify a glide or liquid consonant. However, formant transitions do not
      help listeners identify the vowel to which they are linked; instead, they make
      the competing vowel easier to identify. One explanation is that the formant
      transition region provides a brief time interval during which the competing vowel
      is perceptually more prominent. This interpretation is supported by the
      predictions of two computational models of the identification of concurrent
      vowels that (i) perform a frequency analysis using a bank of bandpass filters,
      (ii) analyze the waveform in each channel using a brief, sliding temporal window,
      and (iii) determine which region of the signal provides the strongest evidence of
      each vowel. Model A [Culling and Darwin, J. Acoust. Soc. Am. 95, 1559-1569
      (1994)] computes the rms energy in each channel at successive time intervals to
      generate running excitation patterns that serve as input to a vowel classifier,
      implemented as a linear associative neural network. Model B uses a temporal
      analysis in each channel to generate running autocorrelation functions, and it
      includes a further stage of source segregation [Meddis and Hewitt, J. Acoust.
      Soc. Am. 91, 233-245 (1992)] to partition the channels into two groups, one group
      providing evidence of the periodicity of the vowel with the dominant F0, the
      other group providing evidence of the competing vowel. Both models predicted
      effects of F0 and formant transitions on identification, but model B provided
      more accurate predictions of the pattern of listeners' identification responses.
      Taken together, the empirical and modeling results support the idea that the
      identification of concurrent vowels involves an analysis of the composite
      waveform using a sliding temporal window, combined with a form of F0-guided
      source segregation.

PMID- 8759968
TI  - Auditory and visual speech perception: confirmation of a modality-independent
      source of individual differences in speech recognition.
AB  - Two experiments were run to determine whether individual differences in auditory
      speech-recognition abilities are significantly correlated with those for speech
      reading (lipreading), employing a total sample of 90 normal-hearing college
      students. Tests include single words and sentences, recorded on a videodisc by a
      male speaker [Bernstein and Eberhardt, Johns Hopkins Lipreading Corpus, The Johns
      Hopkins University, Baltimore, MD, 1986]. The auditory speech was presented with
      a white noise masker, at -7 dB Sp/N. The correlations between overall auditory
      and visual performance were 0.52 and 0.43 in the two experiments, consistent with
      the existence of a modality-independent ability to perceive linguistic "wholes"
      on the basis of linguistic fragments. Subjects in the second experiment also
      identified printed sentences, with 40%-60% portions of the printed characters
      deleted. Performance on this graphical "fragmented-sentences test" also
      correlated significantly with auditory speech recognition, providing a possible
      clue to the cognitive basis for the look-versus-listen correlation. The existence
      of a modality-independent source of variance in speech-recognition abilities may
      be a partial explanation of the difficulty in demonstrating strong associations
      between psychoacoustic measures of spectral or temporal acuity, and speech
      discrimination or identification. Female subjects in both experiments were
      significantly better lipreaders than their male counterparts.

PMID- 8759969
TI  - Inertial cavitation produced by pulsed ultrasound in controlled host media.
AB  - The purpose of this work is to provide measurements in well-characterized media
      in order to better understand inertial (transient) cavitation phenomena. Focused
      transducers with megahertz center frequencies (2.5 MHz, 4.3 MHz) and a clinical
      diagnostic ultrasound system (4.0 MHz) was used to generate pulsed ultrasound to
      induce cavitation. An improved active cavitation detector which utilizes a highly
      focused transducer with much higher center frequency (30 MHz) was used to measure
      the threshold of inertial cavitation. In order to study the effect of the
      concentration of nucleation agents on cavitation thresholds, experiments were
      conducted in distilled water seeded with polystyrene particles. Inertial
      cavitation thresholds were measured for various concentrations of polystyrene
      particles. It was observed that the threshold decreased from 2.5 MPa at
      concentration of about 10(6) particles/ml to 1.6 MPa at a concentration of about
      10(9) particles/ml. The effect of the concentration is not significant for
      smaller changes of concentration. Measurements of the cavitation thresholds were
      then made in specially developed phantom materials to study the effect of
      viscosity on the cavitation threshold when surface tension and other mechanical
      properties of the materials are kept relatively constant. Experimental results
      show that the threshold increases with increasing viscosity, consistent with
      theoretical predictions. Cavitation was also detected in water seeded with
      polystyrene particles using a clinical ultrasound system at an acoustic pressure
      of 3.84 MPa. Results are comparable with those obtained in the laboratory using a
      4.3-MHz focused transducer.

PMID- 8759970
TI  - Template-based automatic recognition of birdsong syllables from continuous
      recordings.
AB  - The application of dynamic time warping (DTW) to the automated analysis of
      continuous recordings of animal vocalizations is evaluated. The DTW algorithm
      compares an input signal with a set of predefined templates representative of
      categories chosen by the investigator. It directly compares signal spectrograms,
      and identifies constituents and constituent boundaries, thus permitting the
      identification of a broad range of signals and signal components. When applied to
      vocalizations of an indigo bunting (Passerina cyanea) and a zebra finch
      (Taeniopygia guttata) collected from a low-clutter, low-noise environment, the
      recognizer identifies syllables in stereotyped songs and calls with greater than
      97% accuracy. Syllables of the more variable and lower amplitude indigo bunting
      plastic song are identified with approximately 84% accuracy. Under restricted
      recordings conditions, this technique apparently has general applicability to
      analysis of a variety of animal vocalizations and can dramatically decrease the
      amount of time spent on manual identification of vocalizations.

PMID- 8759971
TI  - A parametric study of the concentric-ring transducer design for MRI guided
      ultrasound surgery.
AB  - Noninvasive surgery using high-powered, focused ultrasound transducers in
      conjunction with magnetic resonance imaging has been shown to be feasible in
      previous studies. For clinical treatments, the geometry of standard MRI equipment
      limits the space available for ultrasound surgical equipment. This space
      requirement can be reduced in one dimension by using phased arrays to control the
      focal depth, thus eliminating the space required for the motion of a fixed focus
      transducer. Because of its symmetry, an annular array is ideal for changing the
      focal depth. Previous works have simulated, built, and characterized various
      concentric-ring transducers; however, no study has thoroughly examined the
      potential and limitations of the concentric-ring design for MRI guided ultrasound
      surgery. The present work is a systematic examination of the capabilities of the
      concentric-ring array, using numerical simulations to predict the power field,
      temperature distribution, and accumulated thermal dose. The results presented
      here illustrate the effects of ring size, center-to-center spacing
      configurations, number of rings, and radius of curvature on transducer
      performance. A 10-cm radius of curvature transducer with 14 evenly spaced rings
      has been built and characterized in order to verify the accuracy of the numerical
      simulations. The pressure-squared fields produced by this transducer are in
      excellent agreement with the simulated fields.

PMID- 8759972
TI  - An experimentally obtainable heat source due to absorption of ultrasound in
      biological media.

PMID- 8759973
TI  - Profile of a neurology residency in the United Kingdom.

PMID- 8759974
TI  - Correlations between triplet repeat expansion and clinical features in
      Huntington's disease.

PMID- 8759975
TI  - Event-related potentials in HIV infection: evidence for impact of antiretroviral
      treatment.

PMID- 8759976
TI  - Reduction of fasciculations in patients with amyotrophic lateral sclerosis with
      the use of gabapentin.

PMID- 8759977
TI  - Neuroimaging criteria for vascular dementia.
AB  - OBJECTIVE: To examine published imaging criteria that separate cranial computed
      tomographic (CT) scans into grades of increasing support for a diagnosis of
      vascular dementia (VaD). DESIGN: Patients were divided into 4 grades of
      increasing extent of vascular lesions on CT. The frequency of VaD was compared
      between these grades. SETTING: A university department of neurology. PATIENTS:
      Forty-two consecutive patients who underwent neuropsychological assessment for
      possible dementia and who had a CT scan performed within 6 months following any
      stroke causing dementia. Patients with delirium, severe aphasia, and motor and/or
      sensory deficits that impaired neuropsychological testing and patients with mass
      lesions or nonvascular white matter disease shown on CT were excluded. MAIN
      OUTCOME MEASURE: The National Institute of Neurological Disorders and Stroke and
      the Association Internationale pour la Recherche et l'Enseignement en
      Neurosciences criteria for probable VaD. RESULTS: The frequency of VaD was
      greater in patients with grade 1 (7 [50%] of 14, P = .01), grade 2 (2[50%] of 4,
      P = .2), and grade 3(7[78%] of 9, P = .002) scans than the frequency of VaD with
      grade O scans (1[7%] of 15). There was a linear association of the frequencies of
      VaD between imaging grades (P = .0008). In a subgroup of patients with
      neuropsychological deficits caused by cerebrovascular disease, there was a linear
      association of the severity of the deficits between imaging grades (P = .007).
      CONCLUSIONS: We conclude that our criteria can separate CTs into increasing
      levels of support for a diagnosis of VaD. The extent of vascular lesions on CT
      reflects the severity of associated neuropsychological deficts.

PMID- 8759978
TI  - Amyotrophic lateral sclerosis and occupational history. A pilot case-control
      study.
AB  - OBJECTIVE: To assess the association of a number of occupational and industrial
      exposures with amyotrophic lateral sclerosis (ALS). DESIGN: A case-control study
      of ALS cases matched by age and sex to 2 controls each: 1 from a neurologic
      clinic and 1 from a local community. Exposures were ascertained by questionnaire,
      and patients were requested before the interview to be to prepared to supply
      occupational histories. SETTING: Patients with ALS were enrolled at the
      University of Minnesota ALS Clinic in Minneapolis. PATIENTS: Patients with ALS (n
      = 25) were from the University of Minnesota ALS clinic, and clinic controls (n =
      25) were patients with other neuromuscular diseases from the university's Muscle
      Disease Clinic, selected on the basis of clinic enrollment date nearest to that
      of the matched case. Clinic controls were principally patients with myopathies.
      Community controls (n = 25) were selected from the community using a random-digit
      dialing protocol matching on the first 5 digits of the case patient's telephone
      number. RESULTS: The strongest association with disease was exposure to welding
      or soldering materials (odds ratio, 5.0) and the welding industry (odds ratio,
      5.3). Electric plating showed a high odds ratio of 8 (95% confidence interval,
      0.9-72.0), but low statistical significance (P < .07) Several exposures or
      industries, while not statistically different, showed enough difference that to
      ignore them might lead to a Type II error, a result of the pilot nature and small
      sample size. These included paint or pigment manufacturing, the petroleum
      industry, the printing industry, and shipbuilding. CONCLUSIONS: The association
      with welding, soldering, and the welding industry is strong and suggests a need
      for further work. This is despite the small numbers studied, thus making most
      industrial or occupational exposures too limited to draw conclusions or detect
      associations. Perhaps the most obvious candidate from the welding, soldering
      exposure for a common toxin would be lead. Other suggestions of risk were seen
      for paint or pigment manufacture, shipbuilding, electric plating, and the dairy
      industry. The degree of association for these, while high, is not statistically
      significant, and suggests that there may be 1 or more environmental toxins common
      to those industries that need more precise measurement.

PMID- 8759979
TI  - Prevalence of risk factors in spontaneous intracerebral hemorrhage and aneurysmal
      subarachnoid hemorrhage.
AB  - OBJECTIVE: To evaluate whether differences exist in the occurrence of modifiable
      risk factors between aneurysmal subarachnoid hemorrhage and spontaneous
      intracerebral hemorrhage, since these stroke subtypes have frequently been
      combined in epidemiological studies and labeled hemorrhagic stroke. DESIGN: Cross
      sectional survey. SETTING: Helsinki University Central Hospital in Helsinki,
      Finland. PATIENTS: One hundred fifty-six consecutive patients with spontaneous
      intracerebral hemorrhage aged 16 to 60 years (96 males and 60 females) and 281
      patients with aneurysmal subarachnoid hemorrhage (145 males and 136 females) who
      were admitted to an emergency department. MAIN OUTCOME MEASURES: Prevalence of
      several health habits, previous diseases, and medication of patients with
      spontaneous intracerebral hemorrhage were compared with that of patients with
      subarachnoid hemorrhage using multiple logistic regression. RESULTS: Hypertension
      (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.6-4.3), diabetes mellitus
      (OR, 26.4; 95% CI, 3.1-221.6), alcohol intake within the preceding week (for 1
      150 g of alcohol: OR, 2.0; 95% CI, 1.1-3.6; for 151-300 g of alcohol: OR, 1.7;
      95% CI, 0.8-3.8; and for > 300 g of alcohol: OR, 4.4; 95% CI, 2.1-9.1), and
      anticoagulant treatment (OR, 21.8; 95% CI, 2.3-207.3) were all significantly more
      common, but current cigarette smoking (OR, 0.3; 95% CI, 0.2-0.5) was less common
      in patients with intracerebral hemorrhage than in those with subarachnoid
      hemorrhage simultaneously after adjustment for sex, age, and body mass index. In
      males, hypertension (OR, 2.3; 95% CI, 1.1-4.5) and alcohol intake (for > 300
      g/wk: OR, 5.8; 95% CI, 2.2-15.7) were more common, but current smoking (OR, 0.2;
      95% CI, 0.1-0.4) was less common in patients with intracerebral hemorrhage than
      in those with subarachnoid hemorrhage after adjustment for age, body mass index,
      and diabetes mellitus. In females, hypertension (OR, 2.9; 95% CI, 1.4-5.8) and
      anticoagulant treatment (OR, 10.0; 95% CI, 1.0-100.2) were more common in
      patients with intracerebral hemorrhage after adjustment for age and body mass
      index. In univariate statistics, patients with intracerebral hemorrhage were also
      older, more often had previous symptoms of cerebral ischemia, and had higher
      values for body mass index and gamma-glutamyltransferase than did those with
      subarachnoid hemorrhage. CONCLUSIONS: Hypertension, diabetes mellitus,
      anticoagulant treatment, and amount of alcohol taken within 1 week seem more
      commonly to be associated with intracerebral hemorrhage than with subarachnoid
      hemorrhage, which is, however, associated more frequently with cigarette smoking.

PMID- 8759980
TI  - Association of dementia severity with cortical gray matter and abnormal white
      matter volumes in dementia of the Alzheimer type.
AB  - OBJECTIVE: To examine associations between dementia severity and quantitative
      magnetic resonance imaging measures of cortical gray matter volume and abnormal
      white matter volume in 52 patients diagnosed with probable Alzheimer disease.
      DESIGN: Analysis of the relationship between magnetic resonance imaging volume
      measures and dementia severity using multiple regression and Pearson
      correlations. SETTING: Alzheimer's Disease Research Center, University of
      California, San Diego. PARTICIPANTS: Twenty-three men and 29 women with probable
      Alzheimer disease (average age, 71.7 years; average education, 13.3 years). MAIN
      OUTCOME MEASURES: The Mattis Dementia Rating Scale (MDRS) and the Mini-Mental
      State Examination. RESULTS: Using simultaneous multiple regression, magnetic
      resonance imaging volumetric measures of cortical gray matter and abnormal white
      matter were independently associated with dementia severity measured by either
      the MDRS or the Mini-Mental State Examination. Cortical gray matter volume and
      abnormal white matter volume also made independent contributions to performance
      in 4 of 5 cognitive domains assessed by the MDRS. Regional analysis indicated
      that limbic cortical gray matter volume and nonlimbic cortical gray matter volume
      were also correlated with the MDRS score; however, in the regression analysis the
      individual gray matter measures were not independently associated with MDRS
      performance. A similar analysis revealed statistically independent relationships
      of limbic gray matter volume and abnormal white matter volume, but not nonlimbic
      cortical gray matter volume, to Mini-Mental State Examination performance.
      CONCLUSIONS: Quantitative magnetic resonance methods provided strong evidence
      that cortical gray matter volume, which may reflect atrophy, and abnormal white
      matter volume are independently related to dementia severity in probable
      Alzheimer disease: lower gray matter and higher abnormal white matter volumes are
      associated with more severe dementia.

PMID- 8759981
TI  - Sporadic corticosteroid pulses and osteoporosis in multiple sclerosis.
AB  - BACKGROUND: Bone mineral density is reduced in patients with multiple sclerosis
      (MS), but the reduction has not been shown to correlate with steroid use
      retrospectively. OBJECTIVE: To prospectively measure bone density following a
      single corticosteroid pulse using dual energy x-ray absorptiometry. PATIENTS AND
      METHODS: Thirty acutely relapsing patients with MS were given 1000 mg of
      methylprednisolone intravenously daily for 3 days followed by an oral prednisone
      taper for 2 weeks. The bone density was determined at the lumbar spine and
      femoral neck prior to treatment. Seventeen patients were reevaluated 2,4, and 6
      months following treatment. RESULTS: Prior to treatment, bone density in patients
      with MS was already reduced at the femoral neck compared with an age-matched
      reference population, but the degree of this reduction did not correlate with
      prior steroid exposure. Lumbar density, in contrast, was normal. Following the
      steroid pulse, lumbar bone density increased, becoming 1.7% greater than baseline
      6 months later (P = .02). Femoral bone density did not change on average, but the
      patients who required a cane or walker for ambulation had a 1.6% decrease in
      femoral bone density, while those with better ambulation had a 2.9% increase (P =
      .04). CONCLUSIONS: Bone density is decreased in MS. A single corticosteroid pulse
      did not reduce bone density in fully ambulatory patients with MS and multiple
      pulses did not have a cumulative effect on bone density in retrospective
      analysis. The change in femoral density in poorly ambulatory patients may have
      been related to inactivity rather than the steroid pulse.

PMID- 8759982
TI  - Neuropsychological characterization and detection of subclinical hepatic
      encephalopathy.
AB  - OBJECTIVE: To elucidate the nature of the neuropsychological deficits associated
      with subclinical hepatic encephalopathy. DESIGN: Prospective study comparing the
      performance of patients with liver disease and carefully matched normal controls
      on a short but comprehensive neuropsychological test battery. SETTING: A
      university medical center. PARTICIPANTS: Twenty patients with cirrhosis (10
      alcoholic and 10 nonalcoholic) and 20 controls carefully matched on the basis of
      age, sex, education, and alcohol history. RESULTS: The cirrhotic patients
      exhibited relatively selective deficits in complex attentional and fine motor
      skills, with preservation of general intellectual ability, memory, language and
      visuospatial perception. CONCLUSIONS: This pattern of neuropsychological deficits
      suggests a subcortical pathophysiology, possibly reflecting involvement of the
      basal ganglia. These neuropsychological findings are consistent with recent
      neuroradiological, electrophysiological, and neurophysiological research
      implicating basal ganglia involvement in cirrhosis.

PMID- 8759983
TI  - Safety and tolerance of multiple doses of intramuscular fosphenytoin substituted
      for oral phenytoin in epilepsy or neurosurgery.
AB  - BACKGROUND: Safety, tolerability, and pharmacokinetics of fosphenytoin sodium, a
      water-soluble phenytoin prodrug, were investigated after a temporary substitution
      of intramuscular fosphenytoin for oral phenytoin sodium in 240 epileptic or
      neurosurgical patients taking oral phenytoin sodium (100-500 mg/d). METHODS:
      Patients were randomly assigned to 1 of 2 parallel groups. During screening and
      follow-up, patients were maintained on a regimen of oral phenytoin at an
      individualized dose. During treatment, the phenytoin-treated patients received
      intramuscular placebo and their prescribed dose of oral phenytoin; the
      fosphenytoin-treated patients received oral placebo and intramuscular
      fosphenytoin equimolar to their phenytoin dose. RESULTS: Both groups had similar
      types and frequencies of mild to moderate adverse events. Fosphenytoin was as
      well tolerated as intramuscular placebo at the injection site. Intramuscular
      fosphenytoin equimolar to a patient's oral phenytoin dose produced equal or
      greater plasma phenytoin concentrations. CONCLUSIONS: Dosing adjustments are not
      required when intramuscular fosphenytoin is temporarily substituted or oral
      phenytoin therapy is resumed. Intramuscular fosphenytoin is a safe and well
      tolerated alternative to oral phenytoin when oral administration is not feasible.

PMID- 8759984
TI  - The potential contribution of the polymerase chain reaction to the diagnosis of
      tuberculous meningitis.
AB  - OBJECTIVE: To examine diagnostic utility of polymerase chain reaction (PCR) on
      cerebrospinal fluid (CSF) in tuberculous meningitis (TBM). DESIGN: Comparison
      study. SETTING: Referral center for tuberculosis diagnosis and treatment in Ho
      Chi Minh City, Vietnam, and research laboratory in Amsterdam, the Netherlands.
      PATIENTS: One hundred thirty-six consecutive patients, aged 4 months to 85 years,
      with features compatible with TBM seen during a 12-month period. MEASUREMENTS:
      Clinical examination; cytology; Gram, india ink, and Ziehl-Neelsen staining;
      culture of CSF for bacteria, mycobacteria, fungi, and viruses; and CSF chloride,
      protein, and glucose. All these tests were performed in Vietnam. The PCR on CSF
      was performed in the Netherlands. RESULTS: Patients were managed in Vietnam
      without knowledge of PCR results. Based on clinical grounds and the results of
      initial CSF microscopy, antituberculous treatment was given to 104 patients, 66
      of whom had evidence of extraneural tuberculosis. Among the 39 patients with
      confirmed TBM (ie, positive Ziehl-Neelsen staining or culture or PCR results for
      Mycobacterium tuberculosis), PCR detected 32 patients (82%), 1 case was proven
      positive through microscopy and 17 (44%) had positive culture results. There were
      no false-positive PCR results. In 99 patients with a final diagnosis of confirmed
      or probable TBM (ie, clinical features of TBM and response to antituberculous
      treatment), PCR had a sensitivity of 32%; culture, 17% and microscopy, 1%.
      CONCLUSIONS: Many patients who respond to treatment for TBM do not have M
      tuberculosis in the CSF identifiable by microscopy, PCR, or culture. Polymerase
      chain reaction on CSF is the best method for the laboratory diagnosis of TBM.
      Polymerase chain reaction is especially useful for the early diagnosis of TBM in
      those without active extraneural tuberculosis.

PMID- 8759985
TI  - Posttraumatic Amnesia as a predictor of outcome after severe closed head injury.
      Prospective assessment.
AB  - OBJECTIVES: To identify the demographic and clinical variables related to the
      duration of posttraumatic amnesia after severe closed head injury; to evaluate
      the usefulness of posttraumatic amnesia duration in predicting outcome at the
      time of hospital discharge and at 6 months after injury. SETTING: Four clinical
      centers located in primary care hospitals. PATIENTS: Three hundred fourteen
      severely injured subjects aged 16 years or older who did not have trauma as a
      result of a penetrating injury and came out of coma before hospital discharge.
      INTERVENTIONS: Approximately half of the subjects were administered phenytoin
      sodium for some period after termination of coma; 17% were administered
      dexamethasone and 41% morphine sulfate. MAIN OUTCOME MEASURES: Galveston
      Orientation and Amnesia Test scores defined the duration of posttraumatic
      amnesia. The Glasgow Outcome Scale was used to grade outcome at the time of
      hospital discharge and at 6 months. RESULTS: Older age, low initial Glasgow Coma
      Scale score, nonreactive pupil(s), coma duration, and use of phenytoin were
      associated with a longer duration of posttraumatic amnesia. Poor pupillary
      response, time in coma, and duration of posttraumatic amnesia and use of
      phenytoin was predictive of the 6-month outcome. CONCLUSIONS: The results support
      the prognostic usefulness of prospectively measuring duration of posttraumatic
      amnesia after termination of coma. Pending replication, our findings suggest that
      posttraumatic amnesia duration may be a useful surrogate outcome measure for
      clinical trials involving interventions for acute head injury.

PMID- 8759986
TI  - Multiple sclerosis in Italy. A reappraisal of incidence and prevalence in
      Ferrara.
AB  - BACKGROUND: Previous descriptive surveys on multiple sclerosis (MS) in the
      province of Ferrara, northern Italy, carried out by our own epidemiological
      research group, pointed out that this area was not at low-medium risk for MS.
      OBJECTIVE: To verify the morbidity estimates and update the temporal trend of MS.
      DESIGN AND METHODS: We used a complete enumeration approach by reviewing all the
      possible sources of case collection available in Ferrara for 1965 through 1993.
      We included all patients with definite and probable MS according to the criteria
      of Poser et al. RESULTS: The mean annual incidence rate was 2.3 per 100,000
      population (95% confidence interval, 2.0-2.6 per 100,000), 3.0 per 100,000 for
      women and 1.5 per 100,000 for men. On December 31, 1993, 249 patients (170 women
      and 79 men) suffering from definite or probable MS were living in the province of
      Ferrara, giving a crude prevalence rate per 100,000 population of 69.4 (95%
      confidence interval, 61.2-78.7), 90.8 for women and 46.0 for men. CONCLUSION: The
      data confirm that in Ferrara, MS occurs more frequently than previously suggested
      by the latitude-related epidemiological model, supporting the view that northern
      Italy is a high-risk area for the disease. While the prevalence rate is much
      higher than in our previous studies, probably owing to the increasing survival of
      the patients because of improving supportive care, the incidence rates, similar
      in magnitude to those observed in high-risk areas of northern and central Europe,
      have remained relatively stable over time.

PMID- 8759987
TI  - Beneficial effects of corticosteroids on ocular myasthenia gravis.
AB  - OBJECTIVE: To determine if moderate-or low-dose corticosteroid therapy can reduce
      the diplopia and frequency of deterioration to generalized disease in ocular
      myasthenia gravis. DESIGN: Retrospective record review. SETTING: Two university
      based neuro-ophthalmology services. PATIENTS: All 32 patients with ocular
      myasthenia gravis, treated with prednisone, followed up for a minimum of 2 years
      were included. Patients were treated with 1 or more courses of daily prednisone
      (highest initial dose, 40-80 mg) gradually withdrawn over 4 to 6 weeks.
      Subsequently, in 6 patients, 2.5 to 20 mg of prednisone was given on alternate
      day. OUTCOME MEASURES: Diplopia in the primary position or downgaze diplopia and
      generalized myasthenia gravis after 2 years of follow-up. RESULTS: Diplopia,
      which was initially found in the primary position in 29 patients and in the
      downgaze position in 26 patients, was absent in 21 patients at 2 years.
      Generalized myasthenia gravis occurred in 3 patients at 2 years. Elevated serum
      acetylcholine receptor antibody levels and abnormal electromyography findings
      were not predictive of worsening. No patient experienced a major steroid
      complication. CONCLUSIONS: Moderate-dose daily prednisone for 4 to 6 weeks,
      followed by low-dose alternate-day therapy as needed, can control the diplopia in
      patients with ocular myasthenia gravis. The frequency of deterioration to
      generalized myasthenia gravis at 2 years may be reduced; 9.4% in this study
      compared with more than 40% previously reported frequency. Corticosteroids may be
      useful even when ocular motor dysfunction is not normalized.

PMID- 8759988
TI  - Gustave Dax and the early history of cerebral dominance.
AB  - In 1863, 2 years before Paul Broca published his heralded paper on the special
      role of the left hemisphere in speech, Gustave Dax sent a paper to the Academie
      de Medecine in Paris, France. His lengthy submission included an insightful
      memoir presumably written by his father Marc in 1836 and supportive material that
      he had collected himself. The present article examines the events leading to
      Gustave's 1863 submission to the Academie. It also presents an English
      translation of the negative response that this paper received and a translation
      of the short article that Gustave published in 1865. These materials help to show
      how cerebral dominance was first discovered, how it was made public, and how the
      first advocates of the concept were judged by their contemporaries.

PMID- 8759989
TI  - Progressive deterioration of intellect and motor function occurring several
      decades after cranial irradiation. A new facet in the clinical spectrum of
      radiation encephalopathy.
AB  - OBJECTIVE: To report the cases of 2 patients who developed the features of
      radiation encephalopathy 33 and 28 years after cranial irradiation. DESIGN: Case
      reports; clinical data were available for 2 years in each instance. CONCLUSION:
      Latent intervals approaching 2 decades have been reported in cases of radiation
      necrosis following cranial irradiation, but a similar or greater delay before the
      onset of radiation encephalopathy has not been described previously. This report
      indicates that a diagnosis of radiation encephalopathy must be considered when
      any individual who has received cranial irradiation presents with deterioration
      in intellectual or motor function, whatever the interval.

PMID- 8759990
TI  - Spontaneous spinal epidural hematoma. Another neurologic complication of cocaine?
AB  - OBJECTIVES: To describe a patient with a spontaneous spinal epidural hematoma
      associated with cocaine use and to present issues related to pathogenesis and
      management of this potential complication. DESIGN: Case report. SETTING:
      Municipal hospital. CASE: A spontaneous spinal epidural hematoma developed at the
      thoracic level in a 62-year-old man in association with cocaine use. Clinical,
      laboratory, and radiologic data are presented. MAIN OUTCOME AND RESULTS: The
      patient was treated medically with intravenous and oral dexamethasone sodium
      phosphate. His neurologic status gradually improved during a 12-day
      hospitalization. CONCLUSION: Cocaine use should be considered in the evaluation
      of spontaneous spinal epidural hemorrhage.

PMID- 8759991
TI  - [Immediate knowledge and ad hoc knowledge].

PMID- 8759992
TI  - [Obstetric quality assurance].

PMID- 8759993
TI  - [What does the Danish population know about the scientific ethics committees?].
AB  - The Danish system of research ethical committees (RECs) was established in 1978
      and formal legislation on RECs was passed in 1992. We have investigated the
      general knowledge about the RECs through a telephone survey of a random sample of
      the adult Danish population. Among the 1137 respondents only 342 (30%) were aware
      of the existence of an official body which controls medical research, and only a
      small minority was aware of the composition of the RECs and that the laymembers
      outnumber the professional members. Knowledge about RECs was positively
      correlated to higher education, young age, and being male. It is argued that
      there is a need for increased public information about the existence and
      composition of the Danish RECs.

PMID- 8759994
TI  - [Birth statistics for "standard populations". A basis for obstetric quality
      development].
AB  - Using standard populations like "standard-primipara" (normal pregnancy, singleton
      term delivery and cephalic presentation) and "caesarean secundapara" (previous
      caesarean section and second birth) as the basis for interunit comparisons of
      maternity care will control for differences in casemix that may be seen at
      different units, thereby increasing the validity of comparisons. Focusing on
      clinically meaningful subsets of the population may have the additional benefit
      of clarifying the relationship between everyday clinical decision making, and the
      statistics from medical birth registration. Birth registry data from
      Rigshospitalet, Hvidovre Hospital and Herning Centralsygehus 1993-1994 have been
      used to illustrate the association between local quality improvement activities,
      on the one hand, and rates of interventions and foetal outcome in "standard
      primipara" on the other.

PMID- 8759995
TI  - ["The withered arm". A multifocal motor neuropathy and considerations in
      differential diagnosis].
AB  - Multifocal motor neuropathy (MMN) is a newly recognized disorder with a
      characteristic clinical picture. The diagnosis of MMN is established by the
      presence of a specific electrodiagnostic abnormality, conduction block confined
      to motor axons, and in some instances by the associated high titers of anti-GM1
      antibodies. Clinical improvement may be achieved by treatment with intravenous
      immunoglobulin or cyclophosphamide, which underlines the importance of
      recognizing these patients. We present two patients with slowly progressive
      predominantly distal weakness and muscle wasting of an upper extremity
      characteristic of MMN. Extensive electrophysiological examinations are necessary
      to demonstrate conduction block of motor axons, which distinguishes patients with
      MMN from patients with motor neuron disease. Other diagnostic possibilities are
      discussed.

PMID- 8759996
TI  - [Induced abortion after the 12th week of pregnancy in the county of Arhus 1993
      1994. Psychological consequences].
AB  - The records of all women applying for permission to have an abortion performed
      after the 12th week of pregnancy during a one-year period in the County of Aarhus
      were continuously reviewed, and the women who had the abortion performed due to
      psychosocial reasons were interviewed with a questionnaire at the time of the
      abortion and again four months later. Of the 76 women who applied for permission
      for a late abortion the following were excluded from the study: 31 who had the
      abortion because a malformed child was suspected, six women who did not have the
      abortion although permission had been given, five women who did not receive
      permission, four who were under 18 years of age, one who had a miscarriage, 10
      who were from another country of origin and did not understand Danish and finally
      four women who were allowed an abortion on a medical indication and who were
      either in hospital or in jail. Fifteen women were questioned concerning their
      age, length of pregnancy and psychological and social histories and were asked to
      fill out a depression scale. The data showed that none of them had planned their
      pregnancy and they had had no symptoms of pregnancy until the time at which they
      applied for the abortion. None of them regretted the abortion afterwards; half of
      the women were under psychological strain at the time of application, and a few
      of them had even more psychological symptoms four months after the abortion.
      Although they had many social problems, physical complications and psychological
      problems only a few of the women had seen a doctor in the four month period
      between the abortion and the follow-up.

PMID- 8759997
TI  - [Tuberculosis in Greenland 1994. A minor outbreak of new cases of tuberculosis in
      the village of Kullorsuaq].
AB  - An outbreak of pulmonary tuberculosis was detected in 1994 in a small village,
      Kullorsuaq, located 300 kilometres north of Upernavik in the north-western part
      of Greenland. The inhabitants of Kullorsuaq mainly live off subsistence, hunting,
      seal-hunting and fishing. Too many people were living in bad housing and with a
      general lack of sanitation facilities. There had been a few serious cases of
      pulmonary tuberculosis in 1993, and when three new cases of tuberculosis in
      school children were diagnosed in April 1994, the authorities arranged for all
      292 inhabitants of Kullorsuaq to be examined by chest X-ray. We defined
      tuberculosis as an infiltration seen on X-ray when tuberculosis was discovered in
      the near environment together with a strongly positive mantoux test. We found 20
      cases of tuberculosis, two were smear positive by microscopy, both confirmed by
      culture, and a further five cases were diagnosed only by culture. By DNA
      fingerprint-analysis we found all culture positive cases to be exactly alike. Two
      cases of lung cancer were also diagnosed.

PMID- 8759998
TI  - [Infections in connection with epidural catheterization].
AB  - Seventy-eight patients with culture-positive epidural catheters were studied.
      Fifty-nine had symptoms of exit site infection and 11 patients had clinical
      meningitis, two of whom also had en epidural abscess. This corresponds to a local
      infection incidence of at least 4.3% and an incidence of central nervous system
      infection of at least 0.7% at Odense University Hospital. The patients with
      generalized symptoms of infection had been catheterized for a longer time, and
      were older than patients with only local symptoms of infection. The
      microorganisms isolated from the epidural catheters were coagulase- negative
      staphylococci (41%), Staphylococcus aureus (35%), Gram-negative bacilli (14%) and
      other bacteria (10%). The Gram-negative bacilli and S. aureus caused serious
      infections more frequently than the others. We discuss the symptoms and diagnosis
      of spinal epidural abscess and propose prophylactic and diagnostic guidelines for
      epidural catheter-related infections.

PMID- 8759999
TI  - [Primary cerebral non-Hodgkin's lymphomas and primary malignant brain tumors in a
      well-defined geographical area. Population-based data from the registry of non
      Hodgkin's lymphoma in western Denmark, LYFO and the cancer registry, Kraeftens
      Bekaempelse].
AB  - In a Danish population-based non-Hodgkin's lymphoma (NHL) registry (LYFO)
      representing a population of 2.7 million all new cases of NHL were registered
      from 1st January 1983 to 31st May 1994. Incidence data of primary malignant
      tumours of the brain and central nervous system in western Denmark for the period
      1971-1990 have been obtained from the Danish Cancer Registry. During the
      approximate 11-year period 3124 new cases of NHL were registered. Of these, 1152
      (37%) were extranodal and 48 were non-AIDS related primary central nervous system
      lymphomas (PCNSL) accounting for 4.2% of extranodal NHL and 1.5% of all NHL,
      respectively. The average annual incidence rate of non-AIDS related PCNSL during
      the period was 1.56 cases per million population (age range: 15-85 yrs, median:
      62 yrs, M/F ratio: 1). In a 23-year period there was no trend towards an
      increasing incidence of non-AIDS related PCNSL in a well-defined population.
      PCNSL accounted for 1.7% of all primary malignant brain tumours. Incidence of
      primary malignant brain tumours was stable, except for age ranges over 70 years.
      Histologically, 85% were high grade, centroblastic diffuse (60%) and
      immunoblastic lymphoma (13%) (Kiel classification). No T-cell lymphomas were
      detected. Treatment included surgical resection, whole brain irradiation (WBRT)
      and chemotherapy. Median survival for those receiving either WBRT or WBRT and
      chemotherapy was eight months and 20 months, respectively (p = 0.78). Overall
      survival was 53%, 38% and 26% at one, two and five years. Cox-regression analysis
      identified only one factor having independent impact on survival in performance
      score > or = 2 (PCNSL p < 0.001, RR = 5.8).

PMID- 8760000
TI  - [Primary cerebral non-Hodgkin's lymphoma. Intensive chemotherapy supported by
      crania radiotherapy].
AB  - Four cases of primary central nervous system lymphomas treated with high dose
      cytosine arabinoside and high dose methotrexate prior to cranial irradiation are
      described. All patients achieved a complete clinical and radiological remission
      following treatment with chemotherapy alone. Three patients are alive with a
      follow-up period of 60, 45 og 24 months, respectively. One patient died 12 months
      after diagnosis at another hospital. Autopsy was not performed.

PMID- 8760001
TI  - [Pseudosarcomatous fibromyxoid tumor in the spermatic cord].
AB  - A case of fibrous pseudotumour in the spermatic cord is described. The patient
      had a large hydrocele, at the edge of which a tumour seven cm in diameter
      consisting of pleomorphic cells of fibrohistiocytic or myofibroblastic type was
      found. The patient has been followed for 18 months, with no signs of recurrence,
      but the biologic potential of this type of tumour has yet to be decided.

PMID- 8760002
TI  - [Assessment of cells from solid tumors in peripheral blood].

PMID- 8760003
TI  - [Assessment and treatment of renal stones].

PMID- 8760004
TI  - Role of polymerase chain reaction in the diagnosis of gastric syphilis.

PMID- 8760005
TI  - Recommendations for the reporting of urinary bladder specimens containing bladder
      neoplasms. Association of Directors of Anatomic and Surgical Pathology.
AB  - The Association of Directors of Anatomic and Surgical Pathology have developed
      recommendations for the surgical pathology report for common malignant tumors.
      The recommendations for carcinomas of the urinary bladder are reported herein.

PMID- 8760006
TI  - The prognostic significance of histomorphometry and immunohistochemistry in giant
      cell tumors of bone.
AB  - Eighty-two cases of giant cell tumor (GCT) were reviewed. Hematoxylin-eosin-and
      hematoxylin, phloxine, saffron, and alcian green-stained sections (82 cases) were
      examined for mitotic rate, the number of giant cells, and the pleomorphism of the
      stromal cells. In 29 cases, the tumor was stained for CD68, alpha 1
      antichymotrypsin (AIACT), S100 protein, Muramidase, and von Willebrand factor
      (factor VIII). The staining properties of mononuclear and multinucleated giant
      cells were compared. Morphometric analysis was performed on 14 cases with a LECO
      2001 computer-assisted image analyzer (LECO Instruments Ltd, Mississauga,
      Ontario, Canada) and included absolute cell count, nuclear area, perimeter,
      roughness, roundness, and aspect and nuclear versus cytoplasmic ratios, measured
      both in the stromal cells and giant cells. The cases were divided into four
      groups: (1) cases with metastasis, (2) cases with recurrence, (3) cases with both
      metastasis and recurrence, and (4) cases with neither metastasis nor recurrence.
      Immunohistochemistry revealed a stronger AIACT than muramidase positivity in
      general. The staining was stronger in stromal cells than in giant cells. Giant
      cells in all tumors were positive for CD68. Stromal cells showed weaker
      positivity for the same stain. The number of asymmetrical mitotic figures was
      significantly greater in group 3 than in group 4 (P < .05). Morphometric
      assessment has identified a statistically significant difference in the aspect
      ratio and the roundness of the nuclei between these two groups. The other
      parameters did not differ significantly. In this article, the significance of
      these findings in prognostication and the histogenesis of the giant cell tumor
      are discussed. Their clinical applicability is yet to be determined.

PMID- 8760007
TI  - Gastric syphilis: polymerase chain reaction detection of treponemal DNA in
      pseudolymphomatous lesions.
AB  - Syphilis is an unexpected diagnosis in the stomach. To establish the diagnosis,
      evidence of Treponema pallidum in the gastric lesion is necessary. However, it is
      sometimes difficult to prove the presence of the organisms by conventional
      methods. The authors describe two cases of early gastric syphilis with
      pseudolymphomatous histology in which T pallidum gene was detected by the
      polymerase chain reaction (PCR) using paraffin biopsy sections. The gastric
      lesion of each case endoscopically and histologically simulated that of malignant
      lymphoma. However, no clonality was proved by immunohistochemistry or PCR gene
      rearrangement analysis. No spirochetal organisms were detected with certainty by
      Warthin-Starry silver stain, whereas the organisms were shown by
      immunofluorescent stain in one patient. A PCR study showed the treponemal DNA in
      both patients, and its validity was supported by a direct sequencing and a
      restriction enzyme digestion. Positive results of serological tests for syphilis
      and regression of the lesions after antisyphilitic treatment were confirmatory of
      the diagnosis. Gastric syphilis should be considered as a differential diagnosis
      when an atypical lymphoid infiltrate fails to show monoclonality. The present PCR
      method would be helpful in showing T pallidum using routinely processed small
      biopsy specimens as the tissue source.

PMID- 8760008
TI  - Pathology of radiation-induced heart disease: a surgical and autopsy study of 27
      cases.
AB  - During the 20 years between 1973 and 1992, 27 patients were identified in whom
      cardiac tissue was available (15 surgical, 10 autopsy, and 2 both) that exhibited
      radiation-related injury. Specimens were assessed for damage to the pericardium,
      valves, myocardium, and coronary arteries. Patients ranged in age from 22 to 76
      years (mean, 49 years), and 19 were men. Among 20 cases with available
      pericardium, 14 (70%) had radiation-related disease including six with an
      effusion, three with constriction, two with both, and three with neither. In 17
      cases with available valves, 12 (71%) showed radiation injury involving 25 valves
      (nine mitral, eight aortic, five tricuspid, and three pulmonary), although
      clinically significant dysfunction was diagnosed in only eight. For the 16
      patients from whom myocardium was available, 10 (63%) exhibited radiation-related
      fibrosis, which was moderate or severe in only the seven who received more than
      3,000 rad (cGy). Among the 13 cases with available coronary arteries, only two
      had unequivocal radiation-induced obstructions (26- and 44-year-old men with
      Hodgkin's disease). In conclusion, radiation injury to the heart includes not
      only constrictive pericarditis and myocardial fibrosis, but also appreciable
      valvular and coronary artery lesions. As patients with malignancies survive
      longer, the surgical relief of radiation-induced heart disease may become more
      prevalent.

PMID- 8760009
TI  - Chronic irradiation enteritis: its correlation with the elapsed time interval and
      morphological changes.
AB  - Twenty-one lesions from 19 patients with chronic irradiation enteritis (CIE) were
      examined to elucidate correlations with the histological findings and either the
      elapsed time interval or the macroscopic features. The lesions were divided into
      the early CIE group (E group; the lesions resected within 2 years after
      irradiation) of 10 lesions and the late CIE group (L group; the lesions resected
      more than 8 years after irradiation) of 11 lesions. Based on the macroscopic
      features, the lesions of CIE were divided into three types: ulcerative stricture
      type (U type; 11 lesions), serosal adhesion type (A type; 6 lesions) and wall
      sclerosing type (S type; 4 lesions). Only A type lesions were observed in the E
      group, and U type lesions were significantly more frequently encountered in the L
      group (9 of 11; 82%) than in the E group (2 of 10; 20%). Moderately to markedly
      degenerated changes of the vessel wall (8 of 11; 73%), enteritis cystica profunda
      (8 of 11; 73%), atypical epithelia (7 of 11; 64%), and the occurrence of fistula
      (2 of 11; 18%) were all significantly more frequently present in the L group than
      in the E group. No radiation-induced colorectal carcinomas were observed. The
      authors thus conclude that CIE is a slowly progressive disease. The late CIE
      showed macroscopically ulcerative stricture type properties with tissue
      degradation, such as fistulas, perforation, and dysplastic epithelia compared
      with early CIE; thus, long-standing CIE should be followed for the early
      identification of further complications. The classification of CIE based on
      macroscopic features is, therefore, considered to be useful to understand the
      clinical course of this disease better.

PMID- 8760010
TI  - Mutations associated with carcinomas arising from pleomorphic adenomas of the
      salivary glands.
AB  - Pleomorphic adenoma (PA) is the most common benign tumor of salivary glands.
      Carcinomas in pleomorphic adenomas (CPAs) may arise by malignant transformation
      of the epithelial components of PAs. Occasionally, transitional zones containing
      cells with histological features intermediate between those of the benign PA and
      carcinomatous components of CPA are identified. After careful microdissection of
      archival microslides, the authors studied 12 cases of CPAs and their attendant
      adenomatous and transitional areas for mutations in the p53, RB, and K-ras genes,
      and at chromosomal loci 5q and 9p. The authors failed to find mutations in the K
      ras gene or 9p locus. A relatively high rate of mutations (loss of heterozygosity
      [LOH] and microsatellite alterations) at the p53 gene were detected in CPAs
      (58%), and at somewhat lower frequencies at the RB gene (33%) and chromosomal
      location 5q (17%). Mutational frequency in the associated transitional and
      adenomatous areas were slightly lower than in the corresponding CPAs. No
      mutations were detected in adenomatous or transitional areas unless they also
      were present in the corresponding CPAs. Mutations of these three genes were
      absent in four cases of CPA, and in seven PAs without malignant change. These
      findings indicate that most CPAs arise from adenomas as the result of mutations
      in the three genes, especially p53. In addition, other, as yet unidentified genes
      may also be involved both in the development of PA and in its malignant
      progression to CPA. Mutational analysis of PAs may provide information of
      prognostic importance.

PMID- 8760011
TI  - Detection of transforming growth factor-alpha protein and messenger RNA in
      hepatobiliary diseases by immunohistochemical and in situ hybridization
      techniques.
AB  - Transforming growth factor-alpha (TGF-alpha) is a cytokines related to cell
      proliferation and transformation. Immunoreactive TGF-alpha protein is expressed
      in regenerating hepatocytes and interlobular bile ducts as well as in
      hepatocellular carcinoma. Although TGF-alpha is thought to play an important role
      in the intrahepatic biliary tree, its role in cellular physiology is poorly
      understood. This study investigates the expression of TGF-alpha and its messenger
      RNA (mRNA) in various hepatobiliary diseases. The authors showed by
      immunohistochemistry that TGF-alpha and its receptor, epidermal growth factor
      receptor (EGFR), were expressed in interlobular bile ducts, proliferating bile
      ductules, and most hepatocytes in various hepatobiliary liver tissues. They also
      showed by Western blot analysis that TGF-alpha protein was present in hepatic
      bile samples obtained from patients with obstructive jaundice. In situ
      hybridization showed that TGF-alpha mRNA was localized in hepatocytes of some
      pathological liver tissues, but it was absent in biliary epithelial cells of the
      same tissues. These findings suggest that TGF-alpha protein is produced by
      hepatocytes, and hepatocyte stimulation occurred as autocrine growth regulation.
      The release of TGF-alpha into hepatic bile caused biliary proliferation and
      transformation through EGFR, present on the existing cell surface membrane of
      biliary epithelial cells.

PMID- 8760012
TI  - Allergic fungal sinusitis: a clinicopathologic study of 16 cases.
AB  - Allergic fungal sinusitis (AFS) has been clinicopathologically defined as a
      noninvasive form of fungal infection. Etiologically, most reported cases have
      been attributed to pigmented dematiaceous fungi. The authors report 16 cases of
      AFS from our institution, along with a review of cases from the literature. The
      patients' age ranged from 8 to 71 years, with a mean age of 25 years. All
      patients were immunocompetent, although six had a strong history of atopy.
      Multiple sinuses were affected in all cases; nine patients had bilateral
      involvement, and seven patients manifested unilateral involvement.
      Histopathologically, all cases were characterized by the presence of "allergic
      mucin," with scattered fungal organisms without invasion of mucosa or bone.
      Fontana-Masson stain identified fungi in all but one case and assisted in
      distinguishing the pigmented dematiaceous organisms from other septated fungal
      forms. Accordingly, Fontana-Masson stain can be useful in confirming the
      diagnosis of AFS in the lack of tissue culture results. Fungal cultures performed
      on six cases grew Exserohilum (three cases), Bipolaris (one case), Drechslera
      (Bipolaris) (one case), and Curvularia (one case). All patients were treated with
      surgical debridement and sinus aeration. Follow-up of at least 6 months was
      obtained in six cases, of which four showed recurrent disease between 8 months
      and 4 years after the initial surgical procedure. A literature review showed that
      the most common etiologic agents were members of the dematiaceous family (81%),
      with the most common genus being Bipolaris (42%), followed by Curvularia (21.3%).
      It is believed that type I and III hypersensitivity reactions underlie the
      pathogenesis of this disease.

PMID- 8760013
TI  - Expression of cytokeratin messenger RNA versus protein in the normal mammary
      gland and in breast cancer.
AB  - It is not known how tightly regulation of cytokeratin (CK) protein expression is
      correlated with transcriptional activity in breast cancer. The level of control
      of CK expression in the normal mammary gland and in breast cancer has been
      assessed by combining in situ hybridization with riboprobes, and with
      immunohistochemistry using monospecific antibodies. In normal mammary gland,
      luminal cells showed abundant hybridization with complementary RNA (cRNA) probes
      for CK7, CK8, CK18, and CK19. Proteins of these CKs were correspondingly
      distributed except for that of CK19, which showed a heterogeneous staining. In
      primary carcinomas, both messenger RNAs (mRNAs) and proteins of CK8 and CK18 were
      generally expressed to a degree similar to that of normal epithelia, but a lower
      level of mRNA and protein of CK18 was observed in metastatic carcinomas. Reduced
      expression of CK7 and CK14 was observed in all carcinomas, and the correlation
      between mRNA and protein for these two cytokeratins was unbalanced, whereas the
      expression of CK19 mRNA and the proportion of its protein-positive cells were
      increased. The results suggest that these major CKs in normal mammary gland
      epithelia are regulated at the transcriptional level except for CK19, which is
      partially under the posttranscriptional control. The alterations observed in
      breast cancer are not only reflected by the reduced or increased expression of
      individual cytokeratins, but characterized by partial loss of the normal
      regulation of cytokeratin expression.

PMID- 8760014
TI  - Quantitation of proliferation-associated markers Ag-NOR and Ki-67 does not
      contribute to the prediction of lymph node metastases in squamous cell carcinoma
      of the vulva.
AB  - A key prognostic parameter for vulvar carcinoma is the presence of lymph node
      metastases. Determination of proliferation markers has been suggested as a method
      to predict lymph node metastases in several tumor types. If this were true in
      vulvar carcinomas, reduced surgical therapy for patients with low-risk vulvar
      carcinoma could be considered. The authors analyzed whether the proliferation
      associated markers silver nucleolar organizer region (Ag-NOR) and Ki-67 are
      predictors for inguinofemoral lymph node metastases in women with vulvar
      carcinoma. The authors also analyzed whether these proliferation markers are
      interrelated. Data were obtained from samples of 145 patients with T1/T2 squamous
      cell carcinoma of the vulva who were treated with vulvectomy and bilateral
      lymphadenectomy. None of these patients received preoperative therapy, and the
      invasion depth of the tumors was more than 1 mm. The median age was 71 years. The
      group consisted of 67 patients with differentiation grade 1, 64 with grade 2, and
      18 with grade 3; 22% (15 of 67) of the patients with grade 1, 45% (29 of 64) with
      grade 2, and 43% (six of 14) with grade 3 had lymph node metastases. Formalin
      fixed, paraffin-embedded sections were stained for proliferation markers Ag-NOR
      and MIB-1 (an equivalent of Ki-67 for fixed material). Both parameters were
      scored at the tumor stroma interface. Ag-NOR number and areas were quantified by
      interactive image analysis and Ki-67 index was scored microscopically with a
      grid. No relation was found between Ki-67 or Ag-NOR and lymph node metastases. A
      relation was found between Ki-67 and mitotic index (MI), but not between Ag-NOR
      and MI or Ki-67 index. Therefore, it is questionable whether Ag-NOR is, indeed, a
      marker for proliferation. The authors conclude that quantitation of Ki-67 and Ag
      NOR does not contribute to the prediction of inguinofemoral lymph node metastases
      in squamous cell carcinoma of the vulva.

PMID- 8760015
TI  - Two consensus primer systems and nested polymerase chain reaction for human
      papillomavirus detection in cervical biopsies: A study of sensitivity.
AB  - Polymerase chain reaction (PCR) is being increasingly used in clinical
      laboratories for the diagnosis of human papillomavirus. From the L1 region, there
      are two commonly used consensus primer systems designated CP5+/G6+ and MY09/MY11.
      Both detect a wide variety of human papillomaviruses (HPVs). In this
      investigation, the authors compared the sensitivity of these approaches with the
      modification of hot-start PCR on 148 neutral-buffered formaldehyde-fixed cervical
      biopsies classified as cervical intraepithelial neoplasia (CIN) I to III. The
      authors chose hot-start PCR because in a previous study it proved more sensitive
      than cold-start PCR. Furthermore, the authors combined GP5+/GP6+ and MY09/MY11 in
      a two-step amplification (nested PCR) to analyze further those cases that proved
      negative with either GP5+/GP6+ or MY09/MY11. The authors found that the two
      consensus primer systems were equally sensitive with a correlation of 98%. By
      using GP5+/GP6+, the authors achieved an HPV positivity rate of 95% and with
      MY09/MY11 94%. Nested PCR did not improve HPV positivity in the CINs included in
      this study.

PMID- 8760016
TI  - Endocervical type glands in urinary bladder: a clinicopathologic study of six
      cases.
AB  - The authors report six cases of glandular lesions made up of endocervical type
      glands in the urinary bladders of women aged 34 to 65 years (mean, 39 years). Two
      patients presented with dysuria, one with painless hematuria, one with complaints
      of pelvic discomfort and hematuria, and one with vaginal discharge. The sixth
      patient was asymptomatic, but on a routine gynecologic examination, a pelvic mass
      was found. On physical examination, three women had masses between the bladder
      and uterus. Four lesions were located in the posterior wall of the urinary
      bladder, one in the dome, and one in the trigone. Four patients underwent biopsy
      of the bladder lesion. One of these patients had undergone a hysterectomy 10
      years earlier. One woman with a pelvic mass between the bladder and uterus
      underwent a hysterectomy, bilateral salpingo-oophorectomy, and partial
      cystectomy. The sixth patient had a transurethral resection of the bladder tumor
      and left oophorectomy. Histologically, all cases showed intermediate to large
      sized irregularly shaped endocervical type glands in the muscularis propria of
      the urinary bladder. Some glands exhibited cystic dilatation and contained
      mucinous secretions. The glands elicited no desmoplastic tissue reaction. The
      intraluminal mucin frequently contained polymorphonuclear leukocytes. In all
      cases, the glands were lined by mucinous, tall, columnar cells and less commonly
      by flattened to cuboidal cells. Rare admixed ciliated cells were also observed.
      The lining epithelium was bland in five cases, but moderate nuclear atypia was
      seen in one case. Mitoses were not observed in any case. Associated lesions
      included endometrial type glands surrounded by elastotic stroma in one case,
      exuberant cystitis glandularis in one case, and a pseudodiverticulum of the
      bladder in one case. Review of the slides from the patient who had had a
      hysterectomy 10 years previously revealed endocervical adenocarcinoma in situ.
      Follow-up (mean = 30 months; range = 6 to 60 months) shows that all patients are
      alive and well, suggesting that the lesion is benign.

PMID- 8760017
TI  - Quantitative image cytometry of infiltrating ductal carcinoma: comparison with
      prognostic parameters and reproducibility of histological grade.
AB  - Quantitative image cytometry was used to compare 18 parameters relating to
      ploidy, nuclear area, and chromatin texture to axillary lymph node status, tumor
      size, and histological grade for 34 infiltrating ductal carcinomas, each of which
      had been graded independently by each of six surgical pathologists. Zinc formalin
      fixed, paraffinembedded tumors were assessed using the Elston and Ellis
      modification of the Bloom and Richardson histological grading scheme. When
      axillary lymph node-negative tumors were compared with those involving four or
      more nodes, % 2 c (diploid) cells, nuclear area, and eight of 12 chromatin
      texture parameters showed statistically significant differences. Carcinomas < 2
      cm had more % 2 c (diploid) cells and fewer % > 4 c (hypertetraploid) cells than
      larger neoplasms. For tumors having nuclear pleomorphism score two versus those
      with score three, nuclear area, four of five parameters related to ploidy level,
      each of five parameters related to run-length matrix features and one of four co
      occurrence matrix features showed significant differences. Nearly all of these
      cytometric parameters also showed significant differences for histological grade
      and mitotic count, which was strongly correlated with nuclear pleomorphism. In
      examining the cytometric parameters in relation to the interobserver
      reproducibility of histological grade and its components, the largest number of
      statistically significant parameters related to the nonreproducibility of nuclear
      pleomorphism. The findings indicate that as the grade of infiltrating ductal
      carcinomas increases, there are fewer % 2 c (diploid) cells and more % > 4 c
      (hypertetraploid) and % > or = 5 c (polyploid) cells. In addition, the cells of
      high grade tumors have larger nuclear areas and more small and large dense
      chromatin clumps, which increase in such number that they tend to join together.
      When compared with the cytometric parameters, nuclear pleomorphism is the most
      sensitive component of grade to nonreproducibility.

PMID- 8760018
TI  - Nasopharyngeal lymphomas: further evidence for a natural killer cell origin.
AB  - The authors report four cases of sinonasal lymphomas with immunophenotypic (four
      cases) and genotypic (three cases) studies. These lymphomas are frequent in
      Oriental countries, but unusual in Western populations, particularly in France.
      Although they have been originally considered as T-cell lymphomas, their origin
      remains unclear, and several authors have recently suggested that they are a
      natural killer (NK)-cell proliferation. The tumor cells of the four cases
      reported here showed characteristics of NK cells. On cryostat sections, they were
      CD3 negative, but CD2 and CD56 positive. The cytoplasm of the tumor cells
      exhibited azurophilic granulations. Using polymerase chain reaction (PCR), no
      clonal rearrangement of the T-cell receptor gamma gene was present. Furthermore,
      clinically, two presented a pharyngeal involvement, and two were also
      characterized by hepatosplenic involvement at the time of the diagnosis. Thus,
      the present cases provide additional evidence toward the NK-cell origin of these
      rare lymphomas. Many sinonasal lymphomas, including the present cases, are
      positive for Epstein-Barr virus (EBV) (LMP-1 antibody and EBER-messenger RNA
      probes). This may suggest an important role of EBV as a local factor in their
      pathogenesis.

PMID- 8760019
TI  - Depletion of stromal and intraepithelial antigen-presenting cells in cervical
      neoplasia in human immunodeficiency virus infection.
AB  - Human immunodeficiency virus-positive (HIV+) women have an increased risk of
      lower genital tract dysplasia and neoplasia, and studies of the central lymphoid
      system suggest that impaired immunosurveillance plays a role in the development
      of their cervical tumors. Intraepithelial and stromal immunocompetent cell counts
      were compared in cervical specimens from 50 HIV+ and 50 appropriately matched HIV
      women (controls) with low and high grade squamous intraepithelial lesions (SIL),
      or carcinoma. Each histological class of HIV+ women displayed fewer
      intraepithelial Langerhans' (S100+) cells (LC) (as already known), and also fewer
      stromal LC and both intraepithelial and stromal (CD68+) macrophages. LC and
      macrophages were reduced in all HIV+ patients, whereas reduction of cervical T
      lymphocytes was found in only immunocompromised subjects (peripheral blood CD4+ T
      cell count < 500/microL). A mucosal quantitative deficiency of antigen-presenting
      cells (APC) thus precedes that of T cells. HIV infection appears to lead to early
      impairment of mucosal immunoreactivity mainly because of defective antigen
      presentation. This impairment may be one mechanism underlying the increased
      frequency of cervical dysplasia/neoplasia, and the enhanced aggressiveness of
      invasive cancers in HIV+ women.

PMID- 8760020
TI  - Pathology of cryptococcal meningoencephalitis: analysis of 27 patients with
      pathogenetic implications.
AB  - In this autopsy series of cryptococcal meningoencephalitis (CME), the authors
      analyzed neuropathologic lesions in 13 human immunodeficiency virus (HIV) and 14
      non-HIV-related cases. Most non-HIV patients did not have immunosuppressive
      predisposing illness. Analysis of pathological findings revealed significant
      differences in the inflammatory response to CME in patients with and without HIV
      infection. None of the acquired immunodeficiency syndrome (AIDS) patients had
      granulomatous inflammation, whereas most non-HIV-associated cases had granulomas,
      supporting a role for cell-mediated immunity in CME. Lymphocytic infiltrate in
      both groups consisted of T cells (CD45RO+). In some non-HIV-associated cases, CME
      was undiagnosed and untreated. In most HIV-associated cases, CME had an
      encephalitic component, resulting in grossly or microscopically visible
      accumulations of fungi within the brain parenchyma, whereas in non-HIV-associated
      cases, CME was often confined to the subarachnoid space and large perivascular
      spaces (Virchow-Robin spaces). In non-HIV-associated cases, yeast forms were
      fewer and showed a more limited distribution. In contrast, many extracellular
      fungi were present in many cases of HIV-associated CME. The principal reactive
      cell in CME in AIDS was brain macrophages and microglia, especially those in the
      perivascular and juxtavascular locations. Reactive astrocytes were limited to
      large destructive lesions and subpial regions. In several patients with HIV
      associated CME, large parenchymal cryptococcomas contained Crytococcus neoformans
      (CN) with cell wall pigmentation, suggestive of melanin. The authors suggest that
      in AIDS patients altered immune functions allow CN to accumulate within the
      brain, predominantly extracellularly, and that deficient macrophage/microglial
      effector function may be responsible for the altered pathology. In addition,
      coexisting CNS processes in HIV-associated CME may contribute to the altered
      pathology. The authors conclude that cryptococcal meningitis is not a disease
      limited to the cerebrospinal fluid (CSF) space but affects the brain more
      significantly than suspected. Therapeutic strategies that enhance the effector
      function of glial cells at the CNS-CSF barrier may be useful for improving the
      response to therapy.

PMID- 8760021
TI  - Clonal Epstein-Barr virus associated cholangiocarcinoma with lymphoepithelioma
      like component.
AB  - Epstein-Barr virus (EBV) has been linked to several undifferentiated carcinomas
      of the aerodigestive tract, especially the nasopharynx, but has not been reported
      in the biliary tract. We here presented a case of an unusual cholangiocarcinoma
      harboring EBV genome in a 47-year-old Chinese woman. Physical examination in 1988
      in Taiwan, including abdominal sonography of the liver, was essentially negative.
      She experienced three episodes of malaria in 1990 when she worked in Ghana,
      Africa, and felt a tumor mass in the epigastrium in October 1992. She received an
      extended left lobectomy for a huge hepatic tumor of 12 x 10 x 5.5 cm in February
      1993. Light microscopy revealed a cholangiocarcinoma composed of both well
      differentiated adenocarcinoma and lymphoepitheliomatous undifferentiated
      carcinoma components. Abundant EBV EBER1 was shown in both tumor components, but
      not in the nontumor liver. Southern blot analysis and polymerase chain reaction
      showed a monoclonal episomal form of EBV, with a genotype characteristic for
      Chinese EBV strain type 1. This finding suggests that the EBV infection preceded
      monoclonal EBV-harboring tumor cell expansion in this case.

PMID- 8760022
TI  - Lymphoepithelioma-like carcinoma of the thyroid gland: lack of evidence of
      association with Epstein-Barr virus.
AB  - Lymphoepithelioma-like carcinomas (LELC) occurring in sites derived from the
      primitive pharynx and foregut have been reported to show a strong association
      with Epstein-Barr virus (EBV), especially in the Oriental population. Primary
      lymphoepithelioma-like carcinoma of the thyroid is an extremely rare neoplasm
      which has been known under many different names, such as intrathyroidal
      epithelial thymoma, primary thyroid thymoma, carcinoma of the thyroid showing
      thymoma-like features, and carcinoma showing thymus-like differentiation
      (CASTLE). We report one such case in a Chinese woman, whose tumor was negative
      for EBV by in situ hybridization technique. This finding suggests that LELC of
      the thyroid may be biologically different from other LELCs, and that detection of
      EBV may aid in diagnosis when the LELC presents initially in lymph nodes or other
      metastatic sites.

PMID- 8760023
TI  - Malignant granular cell tumor: a case report and review of the recent literature.
AB  - We report a case of an extremely rare neoplasm, malignant granular cell tumor
      (MGCT). The tumor occurred in the infratemporal fossa of a 30-year-old man,
      extended to the left orbital base, into the foramen ovale, and invaded the
      mandible. A granular cell tumor (GCT) was diagnosed by fine-needle aspiration and
      core needle biopsy of the mass. The patient underwent a radical subtotal
      debulking procedure followed by radiotherapy. He is alive with recurrent disease
      12 months after presentation. Cytologically, the aspirated material was
      abundantly cellular showing large polygonal cells with ample granular
      eosinophilic cytoplasm, eccentric nuclei, and often prominent nucleoli.
      Histologically, the tumor consisted of solid sheets of similar cells that stained
      strongly with S-100 protein, neuron-specific enolase (NSE), and vimentin. There
      was moderate nuclear pleomorphism and broad zones of necrosis. Four mitotic
      figures per 100 high-power field (HPF) were counted. By electron microscopy, the
      cytoplasm of the tumor cells was filled with lysosomes. Although, some observers
      advocate that the diagnosis of a MGCT should be reserved for cases in which lymph
      node and/or distant organ metastasis is evident, we believe malignancy ought to
      be considered in any GCT with aggressive clinical course defined by persistent
      local recurrence and destruction of neighboring structures. Nuclear pleomorphism,
      necrosis, and presence of any mitotic activity should indicate malignancy.

PMID- 8760024
TI  - Insulin-like growth factor II expression in primary meningeal hemangiopericytoma
      and its metastasis to the liver accompanied by hypoglycemia.
AB  - In situ hybridization and immunohistochemistry were performed to detect insulin
      like growth factor II (IGF2) in tissue sections obtained from a patient with
      hypoglycemia in association with primary meningeal hemangiopericytoma and
      metastatic foci in the liver. High levels of IGF2 mRNA and IGF2 peptide were
      detected in both primary and metastatic tumor cells, although the serum IGF2
      level was within the normal range. Because the serum level of IGF binding protein
      3 was low, whereas the serum insulin level and other endocrinological
      examinations were normal, we speculate that the mechanism of the hypoglycemia was
      associated with the tumor-produced IGF2.

PMID- 8760025
TI  - Mucoepidermoid carcinoma and solid cell nests of the thyroid.

PMID- 8760026
TI  - William Hewson's studies of red blood corpuscles and the evolving concept of a
      cell membrane.
AB  - The botanist Carl Nageli is generally considered to have laid the basis for the
      cell membrane concept by his 1855 study of the osmotic properties of plant cells.
      It is shown here that William Hewson in 1773 presented cogent experimental
      evidence for the concept of a cell membrane in red blood corpuscles. Although his
      work was largely confirmed in subsequent studies, and a cell membrane became an
      attribute of the cell in T. Schwann's cell theory, the idea of a cell membrane
      was rejected by anatomists in 1861 essentially on theoretical grounds, and plant
      physiologists did not mention Hewson's pioneering endeavour. As a consequence,
      Hewson's work has been ignored to this day. A broad cell membrane concept then
      had to await the ingenious work of Overton, started in 1895. The possible reasons
      for these lapses in scientific recognition are analyzed.

PMID- 8760027
TI  - Regulation of ion channels in smooth muscles by calcium.
AB  - Intracellular Ca2+ concentration ([Ca2+]i) plays a central role in regulating
      tone and contractility of smooth muscle cells. In contrast to the "classic" model
      of electromechanical coupling where membrane potential determines [Ca2+]i, it is
      now well established that [Ca2+]i in turn may also affect membrane potential by
      modulating open probabilities of ion channels. Activation by [Ca2+]i of large
      conductance K+ channels, Cl- channels, and nonselective cation channels has been
      described, as well as block of delayed rectifier K+ channels by [Ca2+]i and
      [Ca2+]i-induced inactivation of Ca2+ channels. Therefore, a network consisting of
      positive- and negative-feedback loops regulates [Ca2+]i as well as membrane
      potential. In this context, we review the properties of Ca(2+)-dependent ion
      channels and their functional role in vascular and visceral smooth muscles. Any
      alteration of the "Ca2+ sensitivity" of ion channels is expected to have a
      profound effect on the reciprocal relationship between membrane potential and
      [Ca2+]i. Already several molecular factors determining Ca2+ sensitivity of Ca(2+)
      activated K+ channels have been identified. We provide a working definition for
      Ca2+ sensitivity.

PMID- 8760028
TI  - Hydrolytic and nonhydrolytic interactions in the ATP regulation of CFTR Cl-
      conductance.
AB  - Previously, we showed in the native sweat duct that, in the presence of 0.1-0.5
      mM ATP, nonhydrolyzable ATP analogue adenosine 5'-adenylylimidodiphosphate (AMP
      PNP) can activate cystic fibrosis transmembrane conductance regulator Cl-
      conductance (CFTR GCl) (15). The objective of this study is to determine if 1)
      nonhydrolytic ATP binding alone can activate CFTR GCl after stable
      phosphorylation [in the presence of adenosine 5'-O-(3-thiotriphosphate) and
      phosphatase inhibition cocktail] of CFTR or 2) an ATP hydrolysis (in addition to
      phosphorylation) is required to support subsequent nonhydrolytic ATP regulation
      of CFTR GCl. We show that stably phosphorylated CFTR could only be activated by
      AMP-PNP in the presence of a small background ATP concentration. However, AMP-PNP
      can sustain previously activated CFTR GCl in the absence of ATP, even though Mg2+
      is required for phosphorylation activation of CFTR GCl. However, once stably
      phosphorylated, ATP activation of CFTR GCl is independent of Mg2+. Our results
      show that both hydrolytic and nonhydrolytic interactions regulate CFTR GCl in
      vivo. Nonhydrolytic ATP interaction plays a significant role in both activation
      and deactivation of CFTR GCl.

PMID- 8760029
TI  - Paracrine mediation of calcium signaling in human SK-N-MCIXC neuroepithelioma
      cells.
AB  - Paracrine-mediated Ca2+ signaling in SK-N-MCIXC neuroepithelioma cells was
      evaluated by means of two experimental paradigms. In the first, single SK-N-MCIXC
      cells were microinjected with inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and
      cytoplasmic Ca2+ was monitored by fura 2 digital-imaging microfluorometry. In
      response to Ins(1,4,5)P3 or CaCl2, but not inositol 1,3,4-trisphosphate, an
      increase in cytoplasmic Ca2+ concentration ([Ca2+]i) was observed in injected
      cells and also in neighboring cells. The direction of intercellular propagation
      of Ca2+ signals was influenced by the presence of a flow in the extracellular
      medium and occurred in the absence of any detectable gap-junctional
      communication. The P2 purinoceptor antagonist suramin, but not antagonists of
      other phosphoinositide-linked receptors, blocked cell-to-cell Ca2+ signaling
      initiated by microinjections of Ins(1,4,5)P3. In the second paradigm, conditioned
      medium (CM) obtained from monolayers of SK-N-MCIXC cells elicited increases in
      [Ca2+]i when reapplied to cells on coverslips. The Ca(2+)-mobilizing activity of
      CM was reversibly antagonized by suramin and abolished by pretreatment with
      apyrase. The presence of nucleotide di- and triphosphates in CM was confirmed by
      high-performance liquid chromatography. We conclude that SK-N-MCIXC cells release
      nucleotides that then activate specific receptors on neighboring cells. A rise in
      [Ca2+]i in these cells, and subsequent additional release of nucleotides, serves
      to further the propagation of intercellular Ca2+ signals.

PMID- 8760030
TI  - Plasmin-platelet interaction involves cleavage of functional thrombin receptor.
AB  - We tested the hypothesis that the inhibition of thrombin-induced platelet
      activation by plasmin is mediated via the enzymatic action of plasmin on the
      functional thrombin receptor. We monitored the binding of the anti-thrombin
      receptor antibody [anti-TR-(34-46)] to platelets; this binding is sensitive to
      the cleavage of the thrombin receptor at amino acid residues Arg-41 to Ser-42.
      Plasmin inhibited anti-TR-(34-46) binding in dose- and time-dependent manners.
      The inactive synthetic peptide with the amino acid sequence 40-55 of the thrombin
      receptor (D-FPRSFLLRNPNDKYEPF) was similarly cleaved by thrombin and plasmin to
      an active peptide (SFLLRNPNDKYEPF) that produced robust cytosolic Ca2+ responses.
      At high concentrations, plasmin itself can activate platelets. We explored this
      effect with the use of anti-TR-(1-160). This antibody abolished the cytosolic
      Ca2+ responses to thrombin and to the thrombin receptor-activating peptide SFLLRN
      but did not attenuate the plasmin-induced cytosolic Ca2+ response. Thus plasmin
      inhibits thrombin-evoked platelet activation by cleaving the thrombin receptor,
      but the plasmin-induced cytosolic Ca2+ response is not due to the generation of
      the tethered peptide of the thrombin receptor.

PMID- 8760031
TI  - Stimulation of gastric acid secretion by cAMP in a novel alpha-toxin
      permeabilized gland model.
AB  - It is generally believed that histamine-stimulated gastric acid secretion
      involves a transient elevation of intracellular Ca2+ and the adenosine 3',5'
      cyclic monophosphate (cAMP)-dependent protein kinase (PKA) cascade through
      phosphorylation, whose actions ultimately effect the fusion of H(+)-K(+)
      adenosinetriphosphatase (ATPase)-containing vesicles to the apical plasma
      membrane of parietal cells. To dissect the signaling events underlying gastric
      acid secretion, we have developed a permeabilized gastric gland model using
      Staphylococcus alpha-toxin. The advantage of this model is its ability to retain
      cytosolic components that are required for the secretory machinery. Here we show
      that acid secretion in alpha-toxin-permeabilized glands is a cAMP-dependent
      process, reaching a maximal stimulation at 100 microM cAMP. The cAMP-elicited
      acid secretion, as monitored by the accumulation of the weak base aminopyrine
      (AP), required functional mitochondria or exogenously supplied ATP. Maximal
      stimulation elicited by cAMP for AP uptake by permeabilized glands was 51-85% of
      intact glands. Moreover, secretory activity was potentiated by 0.1 mM ATP. The
      recruitment of H(+)-K(+)-ATPase-rich tubulovesicles into the apical plasma
      membrane was measured using biochemical and morphological assays, thus validating
      the cell activation processes in response to cAMP. From this permeabilized model,
      [gamma-32P]ATP was used to directly phosphorylate target proteins. A number of
      proteins whose phosphorylation-dephosphorylation is specifically modulated by
      cAMP were found. These studies establish the first permeabilized gland model in
      which the resting-to-secreting transition can be triggered and show that cAMP
      mediated phosphorylation is correlated with secretory activity.

PMID- 8760032
TI  - Swelling and cAMP on hyperpolarization-activated Cl- conductance in rat Leydig
      cells.
AB  - We have used the whole cell patch-clamp technique to characterize changes in
      membrane conductance induced by osmotic swelling in mature rat Leydig cells
      dialyzed with ATP (control cells) or adenosine 3',5'-cyclic monophosphate (cAMP)
      plus ATP (cAMP cells). A spontaneous current activation occurs in both groups in
      isosmotic conditions (300/295 mosM in/out). This development is entirely
      counteracted in control cells and partly inhibited in cAMP cells by exposing them
      to a hyperosmotic (350 mosM) bath solution, and these currents increase again in
      a hyposmotic (205 mosM) bath solution. These currents are sensitive to 4
      acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid, a Cl- channel blocker.
      Taken together, the results indicate that, in the control cells (ATP alone) as
      well as in the presence of intracellular cAMP, osmotic swelling activates the
      background hyperpolarization-activated Cl- conductance, osmotic swelling and cAMP
      appearing to act synergistically.

PMID- 8760033
TI  - Effects of cytochrome P-450 inhibitors on ionic currents in isolated rat type I
      carotid body cells.
AB  - Hypoxic chemoreception in the carotid body involves selective inhibition of K+
      channels in type I cells. We have investigated whether cytochrome P-450 may act
      as an O2 sensor coupling hypoxia to K+ channel inhibition, by investigating the
      actions of P-450 inhibitors to modulate channel activity (recorded using patch
      clamp techniques) in type I cells isolated from 8-to 12-day-old rat pups. The
      imidazole antimycotic P-450 inhibitors miconazole and clotrimazole (1-10 microM)
      inhibited the Ca(2+)-activated (KCa) and voltage-gated K+ (Kv) currents in
      isolated type I cells. Single-channel recordings indicated that the KCa channels
      could be inhibited directly by miconazole. Miconazole also irreversibly inhibited
      Ca2+ channel currents. By contrast, acute application of the suicide substrate P
      450 inhibitor, 1-aminobenzotriazole (1-ABT; 3 mM) was without effect on K+ or
      Ca2+ currents. Hypoxia (16-23 mmHg) reversibly inhibited K+ currents and
      prevented the inhibitory actions of miconazole. Furthermore, the inhibitory
      actions of miconazole could be partially reversed by hypoxia. Pretreatment of
      cells for 60 min with 3 mM 1-ABT substantially reduced the inhibitory actions of
      hypoxia on K+ currents. Our results indicate that imidazole antimycotic P-450
      inhibitors can directly and nonselectively inhibit ionic channels in type I cells
      but, more importantly, provide evidence to suggest that hypoxic inhibition of K+
      currents in type I cells is mediated in part at least by cytochrome P-450.

PMID- 8760034
TI  - Changes in action potentials and ion currents in long-term cultured neonatal rat
      ventricular cells.
AB  - A primary culture of neonatal ventricular myocytes isolated from day-old rats was
      established for investigating the changes in action potentials and ion currents
      over long periods. Cells at days 5 and 15 in culture were studied. These changes
      in vitro were compared with those in situ derived from the age-matched freshly
      isolated cells. During primary culture, quiescent cells demonstrated shortening
      of action potential durations (APD) resembling the developmental changes observed
      in situ. The beating cultured cells were not associated with APD shortening.
      Despite constant current amplitudes, the densities of Ca2+ currents (ICa)
      decreased in the quiescent cultures at later ages as a result of cell
      enlargement. ICa densities were maintained in the beating cultured and freshly
      isolated cells. Acceleration in the inactivation of ICa was observed during
      developments both in vitro and in situ. In addition, the densities of transient
      outward currents (Ito) tripled and doubled in the quiescent and beating cells
      during 15-day cultures. However, Ito in beating cultured cells made less
      contribution to APD in contrast to the quiescent cultured and freshly isolated
      myocytes. These findings demonstrate that electrophysiological properties differ
      between two types of long-term cultured cells. ICa densities remained constant in
      the beating cultures, suggesting that cell beating may be required for the
      maintenance of ICa density in developing cardiomyocytes.

PMID- 8760035
TI  - Cytochrome P-450 metabolites mediate extracellular Ca(2+)-induced inhibition of
      apical K+ channels in the TAL.
AB  - We used the patch-clamp technique to study the effect of extracellular Ca2+
      (Ca2+o) on the activity of the apical 70-pS K+ channel in the isolated split-open
      thick ascending limb (TAL) of the rat kidney. Raising Ca2+o from 1.1 to 5 mM
      reversibly reduced the activity of the 70-pS K+ channel in cell-attached patches
      to 16 +/- 2% of the control value within 300 s. In addition, 50 microM neomycin
      mimicked the effect of an increase in Ca2+o on channel activity in cell-attached
      patches and completely inhibited channel activity. The effect of neomycin on the
      channel activity in cell-attached patches is an indirect effect, since addition
      of 50 microM neomycin on the 70-pS K+ channel in inside-out patches reduced only
      the apparent amplitude of the channel current without changing channel open
      probability. We examined further the role of protein kinase C (PKC) and the
      cytochrome P-450-dependent metabolites of arachidonic acid in mediating the Ca2+o
      -induced inhibition of channel activity. Addition of phorbol 12-myristate 13
      acetate (2 microM) reversibly blocked channel activity in cell-attached patches
      to 4 +/- 1% of the control value, whereas 75 nM calphostin C increased the
      channel activity by 115 +/- 10%. Moreover, addition of 1 nM exogenous PKC
      reversibly and completely inhibited the 70-pS K+ channel. However, inhibition of
      PKC with calphostin C (75 nM) only slightly prolonged the time course of the
      effect of Ca2+o on channel activity (370 +/- 40 s) and failed to abolish the
      inhibitory effect of 5 mM Ca2+o on channel activity in cell-attached patches,
      indicating that PKC was not mainly responsible for the effect of Ca2+o on channel
      activity. In contrast, the effect of 5 mM Ca2+o on the apical 70-pS K+ channel
      was completely abolished when TAL tubules were first incubated in the 17
      octadecynoic acid (5 microM)-containing solution, an agent that specifically
      blocks cytochrome P-450 monooxygenase. In conclusion, these data indicate that
      Ca2+o is an important regulator of the apical 70-pS K+ channel and that a
      cytochrome P-450-dependent metabolite of arachidonic acid is involved in
      mediating this inhibitory effect.

PMID- 8760036
TI  - cAMP- and swelling-activated chloride conductance in rat hepatocytes.
AB  - An outwardly rectifying Cl- conductance was identified in primary isolated rat
      hepatocytes, and the whole cell patch-clamp technique was used to characterize
      its properties and mechanisms of activation. With symmetrical Cl(-)-containing
      solutions on both sides and adenosine 3',5'-cyclic monophosphate (cAMP; 100
      microM) in the pipette solution, a large outwardly rectifying conductance (1,014
      +/- 153 pS/pF, n = 20) developed in all cells within 3 min. This cAMP-activated
      conductance was highly anion selective and slowly inactivated at voltages > 80
      mV. It was completely inhibited by the anion channel blocker 5-nitro-2-(3
      phenylpropylamino) benzoic acid (200 microM, n = 6) and partially inhibited by
      4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (150 microM, n = 7). It
      displayed a halide selectivity of I- > Br- > Cl-. In the absence of cAMP, a
      functionally similar conductance was activated by cell swelling. Reduction of
      bath osmolality from 300 to 250 mosmol/kg increased membrane conductance from 64
      +/- 16.4 to 487 +/- 23 pS/pF (n = 4). This swelling-activated conductance was
      also highly anion selective and had identical halide selectivity and blocker
      sensitivity as the cAMP-activated conductance. Although cell swelling was not
      necessary for cAMP activation, cell shrinkage with hyperosmotic bath (350
      mosmol/kg), either before or after exposure to cAMP, inhibited the cAMP-activated
      conductance. By the determination of conductance as a function of bath osmolality
      in the presence and absence of cAMP, it was observed that cAMP shifted the
      osmotic set point for conductance activation without changing either the maximum
      or minimum conductance. In conclusion, both cAMP and cell swelling activate a
      large outwardly rectifying Cl- conductance in rat hepatocytes. Its ionic
      selectivity and sensitivity to channel blockers are identical to those seen for
      swelling-activated Cl- conductances in many cell types. The conductive properties
      are not those of cystic fibrosis transmembrane conductance regulator-mediated Cl-
      conductance. cAMP appears to activate this conductance by altering the volume set
      point of a swelling-activated channel.

PMID- 8760037
TI  - Regulation of HSP70 by PTH: a model of gene regulation not mediated by changes in
      cAMP levels.
AB  - Parathyroid hormone (PTH) activates both adenylate cyclase and phospholipase C in
      target cells, and cloned PTH/PTH-related protein (PTHrP) receptor can mediate
      both responses when expressed in host cells such as LLC-PK1 renal epithelial
      cells. Because calcitonin (CT) is known to augment 70-kDa heat shock protein
      (HSP70) mRNA by an adenosine 3',5'-cyclic monophosphate (cAMP)-independent
      mechanism in LLC-PK1 cells, we examined regulation of HSP70 transcription by PTH
      in these cells. Like CT, human PTH-(1-34) [hPTH-(1-34); 10(-10) to 10(-7) M)]
      increased porcine HSP70 mRNA and human HSP70 promoter-chloramphenicol
      acetyltransferase (CAT) expression within 4 h in LLC-PK1 cells that stably
      express > or = 100,000 PTH/PTHrP receptors per cell. The effect of PTH on HSP70
      mRNA was not mimicked by cAMP analogues, forskolin, phorbol esters, Ca2+
      ionophores, or alpha-thrombin; was insensitive to pertussis toxin; and was not
      due to increased mRNA stability. The upregulation of HSP70 gene transcription by
      hPTH (and CT) was clearly observed even after deletion of the functional heat
      shock consensus element in the promoter region of the human HSP70/CAT reporter.
      Upregulation of HSP70 transcription via endogenous PTH receptors also was
      observed in the osteoblastic cell lines SaOS-2 and ROS 17/2.8. Regulation of
      HSP70 gene transcription by PTH may be a common cellular response to the hormone,
      which, in some cells, may not be mediated by activation of adenylate cyclase or
      protein kinase C.

PMID- 8760038
TI  - Increased sensitivity to 1,25(OH)2D3 in bone from genetic hypercalciuric rats.
AB  - As a model of human hypercalciuria, we have selectively inbred genetic
      hypercalciuric stone-forming (GHS) Sprague-Dawley rats whose mean urine calcium
      excretion is eight to nine times greater than that of controls. A large component
      of this excess urine calcium excretion is secondary to increased intestinal
      calcium absorption, which is not due to an elevation in serum 1,25(OH)2D3, but
      appears to result from an increased number of intestinal 1,25(OH)2D3 receptors
      (VDR). When GHS rats are fed a low-calcium diet, the hypercalciuria is only
      partially decreased and urine calcium excretion exceeds intake, suggesting that
      an additional mechanism contributing to the hypercalciuria is enhanced bone
      demineralization. To determine if GHS rat bones are more sensitive to exogenous
      1,25(OH)2D3, we cultured calvariae from neonatal (2- to 3-day-old) GHS and
      control rats with or without 1,25(OH)2D3 or parathyroid hormone (PTH) for 48 h at
      37 degrees C. There was significant stimulation of calcium efflux from GHS
      calvariae at 1 and 10 nM 1,25(OH)2D3, whereas control calvariae showed no
      significant response to 1,25(OH)2D3 at any concentration tested. In contrast, PTH
      induced similar bone resorption in control and GHS calvariae. Immunoblot analysis
      demonstrated a fourfold increase in the level of VDR in GHS calvariae compared
      with control calvariae, similar to the increased intestinal receptors described
      previously. There was no comparable change in VDR RNA levels as measured by slot
      blot analysis, suggesting the altered regulation of the VDR occurs
      posttranscriptionally. That both bone and intestine display an increased amount
      of VDR suggests that this may be a systemic disorder in the GHS rat and that
      enhanced bone resorption may be responsible, in part, for the hypercalciuria in
      the GHS rat.

PMID- 8760039
TI  - Protein kinase C-dependent phosphorylation of Na(+)-K(+)-ATPase alpha-subunit in
      rat kidney cortical tubules.
AB  - We have previously shown that, in oxygenated rat kidney proximal convoluted
      tubules (PCT), activation of protein kinase C (PKC) by phorbol 12,13-dibutyrate
      (PDBu) directly stimulates Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity.
      PKC modulation of Na(+)-K(+)-ATPase activity by phosphorylation of its alpha
      subunit was the postulated mechanism. The present study was therefore designed to
      investigate the relationship between PKC-mediated phosphorylation of the
      catalytic alpha-subunit and the cation transport activity of the Na(+)-K(+)
      ATPase. In a suspension of rat kidney cortical tubules, activation of PKC by 10(
      7) M PDBu increased the level of phosphorylation of the Na(+)-K(+)-ATPase alpha
      subunit and stimulated the ouabain-sensitive 86Rb uptake by 47 and 42%,
      respectively. Time and dose dependence of the PDBu-induced increase in Na(+)-K(+)
      ATPase activity and phosphorylation was strongly linearly correlated. The effects
      of PDBu on phosphorylation and activity of Na(+)-K(+)-ATPase were prevented by GF
      109203X, a specific PKC inhibitor, whereas H-89, a specific PKA inhibitor, was
      ineffective. These results demonstrate that PKC activation induces
      phosphorylation of the catalytic alpha-subunit of Na(+)-K(+)-ATPase, which may
      participate in the stimulation of its cation transport activity in the rat PCT.

PMID- 8760040
TI  - Modal gating in neuronal and skeletal muscle ryanodine-sensitive Ca2+ release
      channels.
AB  - The bursting behavior of ryanodine-sensitive single Ca2+ release channels present
      in chicken cerebellum endoplasmic reticulum (ER), rat hippocampus ER, and frog
      and rabbit skeletal muscle sarcoplasmic reticulum was established. Unconditional
      dwell time distributions fitted by the maximum likelihood method reveal at least
      three open and closed exponential components. Trains of low open probability
      (P(o)) bursts were interspersed with trains of high P(o) bursts (> or = 0.8) in
      all the ryanodine receptor isotypes tested. The gating kinetics of the Ca2+
      release channels were defined in long recordings by analyzing burst sequences and
      gamma distributions of average intraburst open (T(o)) and closed times (Tc). The
      gamma distributions of T(o) had two gamma components, suggesting the existence of
      two distinct burst types. In contrast, the gamma distributions of Tc had only one
      component. The correlation between consecutive burst pairs was defined in terms
      of T(o) and then statistically tested by 2 x 2 matrix contingency analysis. The
      probability that the ubiquitous sequential burst pattern was generated by random
      occurrence was < 0.01 (two-tailed Fisher's exact test). Temporal correlations
      were observed in all ryanodine receptor isotypes under a variety of experimental
      conditions. These data strongly suggest that single Ca2+ release channels switch
      slowly between modes of gating. We propose that the effects of agonists of Ca2+
      release channels such as Ca2+ itself can be explained as concentration-dependent
      changes in the availability of each mode.

PMID- 8760041
TI  - Angiotensin II type 1 receptor modulation of neuronal K+ and Ca2+ currents:
      intracellular mechanisms.
AB  - Angiotensin II (ANG II) elicits an ANG II type 1 (AT1) receptor-mediated decrease
      in voltage-dependent K+ current (Ik) and an increase in voltage-dependent Ca2+
      current (ICa) in neurons cocultured from newborn rat hypothalamus and brain stem.
      Modulation of these currents by ANG II involves intracellular messengers that
      result from an AT1 receptor-mediated stimulation of phosphoinositide hydrolysis.
      For example, the effects of ANG II on IK and ICa were abolished by phospholipase
      C antagonists. The reduction in IK produced by ANG II was attenuated by either
      protein kinase C (PKC) antagonists or by chelation of intracellular Ca2+. By
      contrast, PKC antagonism abolished the stimulatory effect of ANG II on ICa.
      Superfusion of the PKC activator phorbol 12-myristate 13-acetate produced effects
      on IK and ICa similar to those observed after ANG II. Furthermore, intracellular
      application of inositol 1,4,5-trisphosphate (IP3) elicited a significant
      reduction in IK. This suggests that the AT1 receptor-mediated changes in neuronal
      K+ and Ca2+ currents involve PKC (both IK and ICa) and IP3 and/or intracellular
      Ca2+ (IK).

PMID- 8760042
TI  - Expression and action of parathyroid hormone-related peptide in human cervical
      epithelial cells.
AB  - Parathyroid hormone-related peptide (PTHRP) expression and activity were analyzed
      in normal human ectocervical keratinocytes (HCX) and keratinocytes immortalized
      by transfection with human papillomavirus (HPV) types 16 and 18 DNAs. In normal
      cells, trans-retinoic acid (RA) and 2.0 mM Ca2+ significantly stimulated PTHRP
      mRNA expression and secretion and led to a significant reduction in the rate of
      proliferation. In contrast, the basal level of PTHRP production decreased sharply
      in confluent HCX, and induction by Ca2+ or exogenous growth factors was reduced
      or lost. After stable transfection with HPV16 and HPV18 DNAs, we observed a sharp
      decrease of PTHRP production in high-passage poorly differentiated HCX. Finally,
      addition of exogenous PTHRP-(1-141) inhibited proliferation of both normal cells
      and low-passage well-differentiated HPV16 immortalized cells. High-passage poorly
      differentiated cells were refractory to PTHRP. These results demonstrate that
      PTHRP production varies greatly with the degree of cell proliferation and
      differentiation and suggest that this peptide acts as an autocrine negative
      growth regulator for cervical keratinocytes.

PMID- 8760043
TI  - Angiotensin-converting enzyme inhibitors regulate the Na(+)-K+ pump via effects
      on angiotensin metabolism.
AB  - Treatment of rabbits with angiotensin-converting enzyme (ACE)-inhibiting drugs
      increases Na(+)-K+ pump current (Ip) of isolated cardiac myocytes when
      intracellular Na+ is at near-physiological levels. To examine if effects of ACE
      inhibitors are related to angiotensin metabolism, we measured Ip in myocytes
      isolated from rabbits treated with the AT1 receptor antagonist losartan. Ip was
      increased to levels similar to those after treatment with ACE inhibitors.
      Exposure of myocytes from captopril-treated rabbits to 10 nM angiotensin II (ANG
      II) for 45 min in vitro reduced Ip to levels similar to those of myocytes from
      untreated control rabbits. This rapid response to ANG II suggests that treatment
      with captopril had induced a functional change in preexisting pump units rather
      than synthesis of a new population of pumps. Consistent with this, we could not
      detect a change in Na(+)-K+ pump subunit mRNAs during treatment with captopril.
      The decrease in Ip of myocytes from captopril-treated rabbits induced by ANG II
      in vitro was blocked by pertussis toxin, bisindolylmaleimide I, and
      staurosporine. Exposure of myocytes to phorbol 12-myristate 13-acetate induced a
      decrease in Ip similar to that induced by ANG II. Thus ACE inhibitors regulate
      the Na(+)-K+ pump in myocytes via an effect on angiotensin metabolism. The
      regulatory mechanism appears to include the AT1 receptor, a G protein, and
      protein kinase C.

PMID- 8760044
TI  - Sarcoplasmic reticulum Ca2+ pump in pig coronary artery smooth muscle is
      regulated by a novel pathway.
AB  - Coronary artery smooth muscle expresses an alternative splice (SERCA2b) of the
      sarcoplasmic reticulum (SR) Ca2+ pump gene SERCA2, which is also expressed in
      cardiac muscle (SERCA2a), but how the activity of this transporter is regulated
      in the coronary artery is not known. SERCA2a in the cardiac muscle can be
      regulated via phospholamban or, as recently reported, by a direct phosphorylation
      of this protein by calmodulin kinase (Xu, A., C. Hawkins, and N. Narayanan.
      J.Biol. Chem. 268:8394-8397, 1993). Because both SERCA2a and SERCA2b contain this
      calmodulin kinase phosphorylation site, we examined the effect of endogenous
      calmodulin kinase phosphorylation of the SR Ca2+ pump in the coronary artery. SR
      enriched membranes were isolated from coronary artery smooth muscle and washed in
      ethylene glycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid to remove
      bound calmodulin. When these membranes were incubated with MgATP2- in the
      presence of Ca2+/calmodulin, a 115-kDa protein was phosphorylated. This
      phosphorylated 115-kDa protein was identified as SERCA2b in Western blots and by
      immunoprecipitation using a SERCA2-selective antibody. Preincubating the
      membranes in MgATP2- in the presence of Ca2+/calmodulin stimulated the subsequent
      Ca2+ uptake in the presence of oxalate plus MgATP2- and azide. The stimulation of
      Ca2+ uptake was inhibited by including the SR Ca2+ pump inhibitors thapsigargin
      and cyclopiazonic acid in the Ca2+ uptake medium or by including the calmodulin
      antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide or the calmodulin
      kinase II peptide fragment 290-309 in the phosphorylation solution. Thus an
      endogenous calmodulin-dependent kinase phosphorylated SERCA2b and activated it.
      Phospholamban could not be detected in these membranes in Western blots.
      Therefore, the regulation of the SR Ca2+ pump activity in coronary artery smooth
      muscle may involve a direct phosphorylation of the pump protein by an endogenous
      calmodulin-dependent kinase.

PMID- 8760045
TI  - cAMP- but not Ca(2+)-regulated Cl- conductance is lacking in cystic fibrosis mice
      epididymides and seminal vesicles.
AB  - Cystic fibrosis (CF) reflects the loss of adenosine 3',5'-cyclic monophosphate
      (cAMP)-regulated Cl- secretion consequent to mutations in the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene. In humans, but not mice, with
      CF, the disease is associated with male infertility. The present study
      investigated the relative magnitudes of the cAMP pathways and an alternative
      Ca(2+)-regulated Cl- secretory pathway in primary cultures of the epididymides
      and the seminal vesicles of normal and CF mice. The basal equivalent short
      circuit currents (Ieq) of cultures derived from the epididymides and the seminal
      vesicles from the CF mice were lower (6.0 +/- 0.6 and 4.0 +/- 1.0 muA/cm2,
      respectively) than those from normal mice (11.1 +/- 1.0 and 6.6 +/- 0.6 muA/cm2,
      respectively). Forskolin induced significant Ieq responses in both the epididymis
      (8.0 +/- 0.7 muA/cm2) and seminal vesicles (4.0 +/- 0.5 muA/cm2) from normal
      mice, whereas forskolin-induced changes in Ieq in CF mouse epididymis and seminal
      vesicles were absent, consistent with defective cAMP-CFTR-mediated Cl- secretion
      in CF mice. Ieq responses to agonists (ionomycin, ATP) that raise intracellular
      Ca2+ (Ca2+i) were larger than forskolin responses in normal animals (6.6 +/- 0.9
      and 13.4 +/- 1.8 muA/cm2, respectively) and were preserved in CF (6.5 +/- 0.9 and
      17.1 +/- 1.0 muA/cm2, respectively). We speculate that the fertility of male CF
      mice is maintained by persistent expression of the predominant alternative Ca(2+)
      mediated Cl- transport system in the epididymides and seminal vesicles.

PMID- 8760046
TI  - FK-506 and rapamycin but not cyclosporin inhibit aldosterone-stimulated sodium
      transport in A6 cells.
AB  - The immunosuppressants cyclosporin A (CyA), FK-506, and rapamycin (RAP) have
      multiple actions on target cells that appear to be mediated by interaction of
      drug-binding protein complexes. Both FK-506 and CyA, but not RAP, inhibit the
      Ca2(+)-dependent phosphatase, calcineurin, and in so doing have been found to
      inhibit Na(+)-K(+)-ATPase activity in various nephron segments. Of interest, FK
      506 and RAP, but not CyA, are bound by the steroid receptor-associated FK-506
      binding heat shock protein of 56 kDa, HSP56. To determine the physiological
      effect of this interaction on a steroid-mediated phenomenon, the effect of these
      agents on steroid-mediated Na+ transport in A6 cells was investigated.
      Aldosterone stimulation of Na+ transport and Na(+)-K(+)-ATPase activity are
      significantly inhibited by prolonged incubation with FK-506 and RAP. Although CyA
      inhibits basal Na(+)-K(+)-ATPase activity, it has no effect on aldosterone
      induced Na+ transport or the aldosterone-induced increase in Na(+)-K(+)-ATPase
      activity. FK-506 inhibits the aldosterone-induced synthesis of G alpha i-3
      protein but has no effect on glucocorticoid receptor number as quantified by
      Western blotting. The results suggest that FK-506 and RAP inhibit steroid
      mediated Na+ transport at some pretranslational site. The common interaction of
      these agents with the steroid receptor-associated HSP56 might account for these
      findings.

PMID- 8760047
TI  - Transient activation of K+ channels by carbachol in bovine pigmented ciliary body
      epithelial cells.
AB  - The action of carbachol (CCh) on isolated pigmented ciliary epithelial cells was
      examined using whole cell patch-clamp recording. Application of 100 microM CCh
      caused transient, occasionally oscillatory, increases in the inward and outward
      currents, followed by a long-term decrease in both currents. Caffeine produced
      transient responses similar to those of CCh. The responses to CCh were blocked by
      the muscarinic receptor antagonist atropine and the inositol 1,4,5-trisphosphate
      receptor blocker heparin (200 micrograms/ml in patch pipette). Manipulation of
      the internal ionic concentrations indicated that only K+ conductances were
      affected by CCh. Changing intracellular Ca2+ concentration ([Ca2+]i) with the
      calcium ionophore ionomycin demonstrated that both the inward rectifier K+
      current and the outward current exhibited Ca2+ dependence. There was no Cl-
      current stimulated either directly by CCh or indirectly by modulators of [Ca2+]i,
      and any Cl- currents present arose from osmotic effects. In the short term,
      muscarinic stimulation will activate K+ channels by causing a transient increase
      in [Ca2+]i. This effect only lasts for 1-5 min, however, and, in the long term,
      the conductance decreases below its original level. The effect of such a
      transient increase in [Ca2+]i on secretion would be complex, involving effects on
      gap junction communication between the pigmented and nonpigmented cell layers and
      the activation state of Cl- channels in the nonpigmented cells. This complexity
      probably accounts for the variable reports of the effects of muscarinic
      stimulation of the ciliary body in vivo.

PMID- 8760048
TI  - Dipeptide uptake by adenohypophysial folliculostellate cells.
AB  - Dipeptide uptake was studied in primary cultures from rat anterior pituitaries by
      use of radiolabeled carnosine and the fluorescent dipeptide derivative beta-Ala
      Lys-N epsilon-AMCA (AMCA is 7-amino-4-methylcoumarin-3-acetic acid). Fluorescence
      microscopic studies revealed that the reporter peptide specifically accumulated
      in the S-100 positive folliculostellate cells that do not produce any known
      hormone. The dipeptide derivative was taken up in unmetabolized form by an energy
      dependent saturable process with apparent kinetic constants as follows: Michaelis
      constant, 19 microM; maximum velocity, 5.5 nmol.mg protein-1.h-1. This high
      affinity transporter was strongly affected by inhibitors of sodium/proton
      exchangers and thus appeared to be driven by a proton gradient. Competition
      studies revealed that the peptide transporter exhibits broad substrate
      specificity with a preference for hydrophobic dipeptides. In contrast to free
      amino acids and the pseudotetrapeptide amastatin, tripeptides were also accepted.
      Compounds without an alpha- and beta-amino group, such as captopril, thiorphan,
      and benzylpenicillin, did not affect uptake of the reporter peptide, although
      they were substrates of the well-characterized intestinal and renal dipeptide
      transporters.

PMID- 8760049
TI  - Interactions of external and internal K+ with K(+)-HCO3- cotransporter of rat
      medullary thick ascending limb.
AB  - We studied [K+]i and [K+]o, where subscripts i and o refer to intracellular and
      extracellular, respectively, concentration dependency of the kinetic properties
      of the electroneutral K(+)-HCO3-cotransport, using suspensions of rat medullary
      thick ascending limb (mTAL). With the use of nigericin and monensin, [K+]i was
      clamped at various values, while maintaining [Na+]i = [Na+]o = 37 mM, [HCO3-]i =
      [HCO3-]o = 23 mM, and pHi = pHo = 7.4. As indicated by 2',7'-bis(carboxyethyl)
      5(6)-carboxyfluorescein HCO3(-)-dependent rates of change in pHi, at constant
      [K+]i, increasing the magnitude of the outward K+ gradient by varying [K+]o
      saturated HCO3-efflux with a Michaelis-Menten curve (apparent Michaelis constant
      for [K+]o = 2 mM, Hill coefficient = 1). On the other hand, increasing [K+]i from
      30 to 140 mM, while either [K+]o or the magnitude of the K+ concentration
      gradient was fixed, saturated HCO3- efflux with a sigmoidal curve and yielded a
      Hill coefficient of 3.4 and 50% of maximum velocity at 70 mM [K+]i. These results
      indicate that [K+]i, independent of its role as a transportable substrate for the
      cotransport with HCO3-, has a role as an allosteric activator of the K(+)-HCO3-
      cotransporter. Such an allosteric modulation may contribute to the maintenance of
      net HCO3- absorption despite large in vivo physiological variations of K+
      concentration in the medullary interstitium.

PMID- 8760050
TI  - Apical membrane permeability of MDCK cells.
AB  - The osmotic water permeability (Pf) and permeability to nonelectrolytes were
      determined for the apical membrane of clonal strain Madin-Darby canine kidney
      (MDCK) C12 cells cultured as cysts with the apical membrane facing the
      surrounding medium. Pf and solute permeabilities were calculated from the rate of
      volume change of cysts by digitizing images at 1-s intervals after instantaneous
      osmotic challenge. Image measurement was fully automated with the use of a
      program that separated the image of the cyst from the background by using
      adaptive intensity thresholding and shape analysis. Pf, calculated by curve
      fitting to the volume loss data, averaged 2.4 +/- 0.1 micron/s and was increased
      by addition of amphotericin B. The energy of activation for Pf was high (16.3
      kcal/mol), and forskolin (50 microM) had no effect on Pf. Two populations of MDCK
      cysts were studied: those with two to three cells and those that appeared to be
      composed of only one cell. The Pf of multicell cysts was the same as single cell
      cysts, suggesting that paracellular water flow is not significant. Solute
      permeability was measured using paired osmotic challenges (sucrose and test
      solute) on the same cyst. Urea permeability was not different from zero, whereas
      the permeabilities of acetamide and formamide were consistent with their relative
      oil-water partition coefficients. Our data are similar to values from studies on
      the permeability properties of vesicles of water-tight epithelial apical
      membrane. The combination of the unique model of MDCK apical-out cysts and fully
      automated data analysis enabled determination of apical membrane permeability in
      intact epithelial cells with high precision.

PMID- 8760051
TI  - Measuring volume perturbation of proximal tubular cells in primary culture with
      three different techniques.
AB  - Osmotic cell volume perturbations of rabbit proximal tubule (PT) in primary
      culture were measured using three independent techniques. Automatic cell
      thickness monitoring of PT monolayers revealed that cell volume rapidly increased
      by 39 +/- 2% in hypotonic medium (150 mosM), which was followed by partial
      regulatory volume decrease (RVD). Subsequent incubation in hypertonic medium (500
      mosM) rapidly decreased cell volume by 54 +/- 2% not followed by regulatory
      volume increase (RVI). When cell volume in PT monolayers was derived from
      concentration changes in the trapped fluorescent dyes, fura 2 or 2',7'-bis(2
      carboxyethyl)-5(6)-carboxyfluorescein, osmotically induced cell volume changes
      appeared much smaller (17 +/- 1 and 22 +/- 2% for similar hypo- and
      hypertonicity, respectively). However, changes in fluorescence intensity were
      most often not in agreement with anticipated cell volume changes. With the
      Coulter counter, a much larger shift in cell volume was observed in PT cell
      suspensions. In this situation, cell swelling in hypotonic medium amounted to 74
      +/- 2% but was still followed by partial RVD. Hypertonicity resulted in a
      decrease in cell volume of 42 +/- 3% not followed by RVI. In conclusion, our
      study indicates that automatic cell thickness monitoring of an epithelial cell
      layer cultured on a permeable support provides more reliable data than monitoring
      changes in fluorescence intensity of trapped dyes.

PMID- 8760052
TI  - Inhibition of renin secretion by Ca2+ through activation of myosin light chain
      kinase.
AB  - This study sought to identify specific enzyme(s) involved in the biochemical
      cascade of inhibition of renin secretion through Ca(2+)-calmodulin mediation with
      the use of inhibitors of protein kinase and phosphatases. Inhibition of renin
      secretion mediated by Ca(2+)-calmodulin was induced by incubating rat renal
      cortical slices in K(+)-rich depolarizing medium, producing > 50% inhibition.
      This inhibition was completely blocked by the calmodulin antagonist
      calmidazolium. The inhibitor of protein kinase with broad specificity, K-252a,
      blocked the inhibition of renin secretion. Neither KN-62, a specific inhibitor of
      Ca(2+)-calmodulin-dependent protein kinase II (CaMK II), nor specific inhibitors
      of protein phosphatase 2B (PP2B), cyclosporin A and FK-506, blocked the
      inhibition. On the other hand, all four known inhibitors specific for myosin
      light chain kinase (MLCK), with different chemical structures and mechanisms of
      inhibition (ML-9, ML-7, KT-5926 and wortmannin), almost completely protected
      renin secretion against the inhibition by Ca2+. In particular, ML-9 reversively
      protected > 77% secretion against the inhibition both in K(+)-rich medium alone
      and in combination with the calcium ionophore A-23187 in a concentration
      dependent manner. Together, these findings from our present study provide the
      first evidence, albeit indirect in nature, for the possibility that activation of
      Ca(2+)-calmodulin-dependent MLCK at the downstream of Ca2+ influx into
      juxtaglomerular (JG) cells leads to phosphorylation of 20-kDa regulatory myosin
      light chain (MLC20). Through interaction with actin, the phosphorylated MLC20 may
      play an important role in the inhibitory stimulus-secretion coupling of renin.

PMID- 8760053
TI  - Inhibitory effect of Ca2+ on renin secretion elicited by chemiosmotic stimuli
      through actomyosin mediation.
AB  - We had previously shown that several experimental manipulations, which are likely
      to produce osmotic swelling of renin secretory granules, stimulate secretion of
      renin (C.S. Park, T.W. Honeyman, S. K. Ha, H. K. Choi, C. L. Chung, and C. D.
      Hong. J. Pharmacol. Exp. Ther. 259: 211-218, 1991). In subsequent studies, Ca2+
      was found to block the stimulation of renin secretion evoked by osmotic swelling
      of renin secretion granules [Park, Hong, and Honeyman, Am. J. Physiol. 262 (Renal
      Fluid Electrolyte Physiol. 31): F793-F798, 1992]. Furthermore, evidence from our
      recent studies indicates that myosin light chain kinase (MLCK) might be involved
      in the inhibition of renin secretion through Ca(2+)-calmodulin. In the present
      study we investigate the possibility that MLCK might mediate the inhibitory
      action of Ca2+ on renin secretion stimulated by osmotic swelling of renin
      secretory granules. Rat renal cortical slices were incubated under a variety of
      experimental conditions that would produce osmotic swelling of renin secretory
      granules. Incubation in hypotonic KCl medium, isosmotic NH4Cl or CH3COONH4
      medium, or isosmotic KCl or CH3COOK medium plus nigericin in the absence of Ca2+
      all produced a significant increase in renin secretion 2- to 14-fold (P < 0.001).
      Ca2+ added to all of these media partially or completely blocked the stimulatory
      effects (P < 0.001). This inhibitory effect of Ca2+ was significantly blocked by
      ML-9 (10(-4) M, P < 0.001), a putative specific inhibitor of the Ca(2+)
      calmodulin-dependent MLCK. Taken together, the present findings support the idea
      that the renin secretory response may involve chemiosmotic swelling of renin
      secretory granules. This pivotal step may be regulated by contractile actomyosin
      interaction, which is in turn modulated through the Ca(2+)-calmodulin-dependent
      activity of MLCK.

PMID- 8760054
TI  - Role of protein kinases in regulating sheep erythrocyte K-Cl cotransport.
AB  - K-Cl cotransport in sheep erythrocytes can be activated by treatment either with
      A-23187 and EDTA to reduce concentration of internal ionized Mg [Mg]i) to
      submicromolar levels, with staurosporine, a potent kinase inhibitor, or with N
      ethylmaleimide (NEM). Activation by these maneuvers is prevented and reversed by
      genistein [inhibition constant (Ki) of 15 microM], which inhibits tyrosine
      kinases (TK). The related glycosidated compound genistin, which does not inhibit
      TK, does not inhibit transport, whereas another TK inhibitor, tyrphostin B46,
      inhibits both basal and stimulated transport (Ki of 28 microM). Cotransport
      activation by NEM is prevented and reversed by the phosphatase inhibitor,
      calyculin A, and activation by staurosporine occurs only if cells contain ATP.
      Increasing [Mg]i inhibits cotransport in the presence of calyculin A whether or
      not staurosporine is present as well. Our work suggests that genistein inhibits
      cotransport through a TK and that staurosporine and NEM activate cotransport,
      probably through inhibition of other kinases, causing stimulation through
      dephosphorylation of a protein (possibly the transporter itself) be a
      serine/threonine phosphatase. [Mg]i inhibits cotransport by activating a kinase
      (concentration for half-maximal activation of 10 microM) that phosphorylates this
      protein.

PMID- 8760055
TI  - Cellular mechanisms underlying adenosine actions on cholinergic transmission in
      enteric neurons.
AB  - Whole cell recordings were used to investigate the effects of adenosine and
      several of its analogues on voltage-activated calcium currents (VACC) of
      myenteric and submucosal neurons. Electrophysiological and pharmacological
      properties of the soma VACC recorded in myenteric neurons indicate that they are
      carried through N-type calcium channels, similar to those of the submucosal
      neurons and to those of the calcium conductance that mediates acetylcholine
      release at the submucosal ganglia. Adenosinergic compounds inhibited, in a
      concentration-response and in a voltage-dependent manner, VACC in neurons from
      both enteric plexuses. The pharmacological profile of the receptors that mediate
      this effect was similar to that of the receptors involved in presynaptic
      inhibition in enteric neurons and likely of the A1 subtype. The effects of 2
      chloroadenosine (CADO) on VACC were prevented by pretreatment with pertussis
      toxin (PTX), became irreversible with guanosine 5'-O-(3-thiotriphosphate) (inside
      the pipette), and were abolished with N-ethylmaleimide (NEM; known to uncouple
      receptors from G protein complexes). Intracellular recordings were used to
      further evaluate presynaptic effects of adenosine at the submucosal plexus.
      Adenosinergic compounds reduced the amplitude of fast excitatory postsynaptic
      potentials (EPSPs) by acting at nerve terminals. This effect was insensitive to
      PTX and staurosporine (a protein kinase inhibitor) but was abolished by NEM. CADO
      effects on EPSPs were not reversed by increasing the extracellular calcium
      concentration. In conclusion, activation of A1 adenosine receptors inhibits VACC
      via PTX-sensitive G proteins in myenteric and submucosal neurons. Reduction of
      cholinergic transmission also involves A1 adenosine receptors and appears to
      involve the activation of PTX-insensitive G proteins.

PMID- 8760056
TI  - IFN-gamma modulates CD1d surface expression on intestinal epithelia.
AB  - In vivo, epithelial cells that line the intestine are intimately associated with
      lymphocytes, termed intestinal intraepithelial lymphocytes (iIEL). A putative
      ligand for iIEL on intestinal epithelial cells is CD1d, and recent studies
      demonstrate a surface form of this molecule exists on intestinal epithelia. At
      present, it is not known whether CD1d expression is regulated by cytokines in the
      intestinal microenvironment. Thus we examined the impact of relevant cytokines on
      CD1d at the level of mRNA and cell surface expression. Using a sensitive whole
      cell enzyme-linked immunosorbent assay, we assessed the impact of relevant
      cytokines on CD1d expression on intestinal epithelial cell lines. We were readily
      able to detect CD1d on the surface of T84 cells, a cryptlike intestinal
      epithelial cell line. Epithelial cell exposure to human recombinant interferon
      gamma (IFN-gamma) resulted in increased CD1d expression in a dose- and time
      dependent manner. Polymerase chain reaction amplification of CD1d cDNA revealed a
      time-dependent induction after exposure to IFN-gamma. This IFN-gamma effect on
      CD1d expression was cytokine specific and was evident with epithelial cell lines
      other than T84, including Caco-2 and HT-29 cells. Finally, we were not able to
      detect significant surface expression of CD1a, CD1b, or CD1c on intestinal
      epithelial cell lines in the presence or absence of relevant cytokines. These
      results indicate that CD1d cell surface protein and cellular mRNA, like other
      major histocompatibility complex-related molecules, is cytokine regulated in
      intestinal epithelial cell lines.

PMID- 8760057
TI  - Role for protein phosphatase in the regulation of Ca2+ influx in parotid gland
      acinar cells.
AB  - Stimulation of Ca2+ (and Mn2+) entry in salivary epithelial cells by carbachol,
      or thapsigargin, is mediated by an, as yet, unknown mechanism that is dependent
      on the depletion of Ca2+ from intracellular Ca2+ stores. This study assesses the
      possible role of protein phosphorylation in the regulation of Ca2+ entry in rat
      parotid gland acinar cells. Treatment of cells with the protein phosphatase
      inhibitors okadaic acid, calyculin A, and pervanadate induced a dose-dependent
      inhibition of carbachol and thapsigargin stimulation of Ca2+ and Mn2+ entry. All
      three inhibitors decreased carbachol stimulation of internal Ca2+ release, which
      likely accounts for the inhibition of carbachol-stimulated Ca2+ entry.
      Thapsigargin-induced internal Ca2+ release was not affected by the treatments.
      Additionally, all three phosphatase inhibitors decreased Mn2+ entry into cells
      with depleted internal Ca2+ store(s) (achieved by incubation with either
      carbachol or thapsigargin in Ca2+-free medium). Treatment of cells with phorbol
      12-myristate 13-acetate, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, or
      staurosporine did not affect divalent cation entry into unstimulated cells or
      thapsigargin treated cells. Importantly, when cells with depleted internal Ca2+
      store(s) were pretreated with staurosporine, or K-252a, the inhibition of Ca2+
      entry by calyculin A and okadaic acid, but not by pervanadate, was attenuated.
      Although the effect of pervanadate remains to be clarified, these results
      demonstrate a role for protein phosphorylation in the regulation of divalent
      cation influx in rat parotid acinar cells.

PMID- 8760058
TI  - Effect of low-protein diet-induced intrauterine growth retardation on rat
      placental amino acid transport.
AB  - Given the central role of the placenta in nutrient transport to the fetus, one
      might propose that maternal nutrition would have a regulatory effect on this
      nutrient delivery. We have examined the effect of a low-protein adequate-calorie
      diet on specific amino acid transport processes by the rat placenta. Maternal
      weight, fetal weight, and placental weight were all significantly reduced in dams
      fed a low-protein (5% casein), isocaloric diet when compared with dams pair-fed a
      control (20% casein) diet. Even though maternal serum amino acid levels were
      maintained in the low-protein animals, fetomaternal serum amino acid ratios were
      significantly reduced, suggesting a reduction in nutrient transfer to the fetus.
      Apical and basal membrane vesicles were isolated from the placental trophoblast
      and were used to examine the amino acid transport capacity of both maternal
      facing and fetal-facing membranes, respectively. Na+-dependent neutral amino acid
      transport mediated by system A was decreased in both membrane preparations, while
      transport mediated by system ASC was unaffected. The Na+-dependent anionic amino
      acid uptake by system X(-)AG (EAAC1) was reduced on the basal membrane, while the
      Na+-independent component was similar between the low-protein and control diet
      fed dams. Cationic amino acid uptake was also reduced on both membrane surfaces.
      A decreased steady-state mRNA content for EAAC1 and CAT1 (system y+) suggests
      that reduced synthesis of the transporter proteins is responsible for the
      decrease in transport activity. Taken together, these data support the hypothesis
      that maternal protein malnutrition affects nutrient delivery to the fetus by
      downregulation of specific amino acid transport proteins.

PMID- 8760059
TI  - Dephosphorylation of activated protein kinase C contributes to downregulation by
      bryostatin.
AB  - We show that bryostatin 1 (Bryo) rapidly produces an inactive, incompetent 76-kDa
      form of protein kinase C-alpha (PKC-alpha) in the LLC-MK2 line of renal
      epithelial cells. Bryo, like phorbol 12-myristate 13-acetate (PMA), acutely
      activated PKC, as indicated by autophosphorylation and translocation of PKC
      alpha, the predominant PMA-sensitive isoform expressed by the cells. Bryo
      concomitantly increased the 32P labeling of 80-kDa PKC-alpha by
      autophosphorylation and produced a 76-kDa form of PKC-alpha that lacked
      detectable 32P. The 76-kDa form was in the particulate rather than the cytosolic
      fraction, which suggests that it was produced from activated kinase. Alkaline
      phosphatase treatment of immunoprecipitated PKC-alpha converted the 80-kDa form
      to 76 kDa, but it had no effect on the mobility of the 76-kDa form, suggesting
      that it was not phosphorylated. Pulse-chase labeling of PKC-alpha with
      [35S]Met/Cys indicated that there is a precursor-product relationship between the
      80- and 76-kDa forms, respectively. Inhibition of protein synthesis had no effect
      on the production of 76-kDa PKC-alpha by Bryo. PMA also produced 76-kDa PKC-alpha
      but was less potent and efficacious than Bryo. Bryo produced a more rapid loss of
      80-kDa PKC-alpha protein and total Ca(2+)- and phospholipid-dependent PKC
      activity than PMA. The 76-kDa form is inactive and incompetent because it lacked
      detectable 32P under conditions that strongly autophosphorylated the 80-kDa form.
      We suggest that dephosphorylation predisposes PKC to proteolysis, and greater
      production of the 76-kDa form explains the more efficient downregulation of the
      kinase by Bryo vs. PMA.

PMID- 8760060
TI  - Intestinal epithelial cytoskeleton selectively constrains lumen-to-tissue
      migration of neutrophils.
AB  - Migration of neutrophils (polymorphonuclear leukocytes; PMN) across polarized
      epithelia is asymmetrical: basolateral-to-apical (physiologically directed)
      migration is far more efficient than migration in the reverse direction,
      suggesting the presence of luminal retention signal(s). Following pilot
      observations, we used polarized intestinal epithelial monolayers (T84) to examine
      whether asymmetrical constraint of migration afforded by the epithelial
      cytoskeleton might underlie such retention signals. Rearrangement of epithelial
      cortical F-actin accompanied PMN transepithelial migration (in either direction)
      and was prevented by preloading monolayers with the F-actin stabilizing agent
      phallacidin. Although phallacidin preloading did not influence physiologically
      directed PMN transepithelial migration, such treatment greatly enhanced migration
      in the reverse direction (i.e., effective loss of luminal retention signal). 1,2
      Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) preloading also
      prevented epithelial cortical actin rearrangements and selectively resulted in
      loss of luminal retention signal(s). BAPTA preloading did not influence
      resistance or forskolin-induced Cl- secretion, and phallacidin preloading did not
      influence resistance or carbachol-induced Cl- secretion, suggesting that barrier
      function and surface polarity were maintained under these conditions. These and
      supplementary data suggest that epithelial actin (but not microtubule)
      cytoskeletal reordering asymmetrically influences PMN migration and underlies, at
      least in part, the observed signal that biases for retention of PMN in the
      luminal space.

PMID- 8760061
TI  - Human connexin 43 gap junction channel gating: evidence for mode shifts and/or
      heterogeneity.
AB  - The gating parameters of human connexin 43 (Cx43) gap junction channels were
      determined using dual whole cell patch clamp and methods designed for analysis of
      multichannel recordings. Under steady-state conditions, the mean open time (MOT)
      of Cx43 gap junction channels was computed and it ranged from 0.43 to 5.25 s. The
      computed mean closed times (MCT) varied from 0.21 to 1.49 s. Analysis showed
      that, while the MOT declined with increasing transjunctional voltage (Vj), the
      apparent decline in the MCT with Vj was not statistically significant. The
      calculated open probabilities ranged from 0.50 to 0.95. Inspection of the data
      showed that there was a prolonged decay in junctional current, which had a time
      course of 60-150 s. The analysis excluded the possibility of a homogeneous
      voltage inactivated/deactivated population of independent and identical Cx43 gap
      junction channels. The analysis provided evidence for a homogeneous population of
      Cx43 channels, which can mode shift under the influence of voltage. The latter
      case cannot be distinguished from a heterogeneous population of Cx43 channels in
      which one population is voltage inactivated/deactivated and another is unaffected
      or weakly inactivated/deactivated by voltage.

PMID- 8760062
TI  - Ca(2+)-dependent nitric oxide release in endothelial but not R3230Ac rat mammary
      adenocarcinoma cells.
AB  - We have characterized the ability of several cell types associated with the
      microvasculature of solid tumors to release nitric oxide (NO.) in response to
      increases in cytosolic Ca2+ concentration ([Ca2+]c). EA.hy926 immortalized human
      umbilical vein endothelial cells (EC), rat fibroblasts (RFL), and tumorigenic
      cells isolated from R3230Ac rat mammary adenocarcinoma (MaC) were treated with
      thapsigargin (TG), an inhibitor of Ca(2+)-ATPase. NO. output was measured via a
      chemiluminescence detection system. Baseline NO. output was detectable only for
      EC. TG caused a significant increase in EC NO. output that could be blocked with
      NG-monomethyl-L-arginine and restored with L-arginine. TG did not stimulate NO.
      release from RFL or MaC cells, despite elevating [Ca2+]c in all cells. A Ca(2+)
      dependent isoform of NO synthase (eNOS) was detected by immunoblot only in EC.
      These data indicate that EC, but not RFL or MaC, are capable of Ca(2+)-dependent
      NO. release and suggest that any Ca(2+)-dependent NO. release within this tumor
      is primarily of endothelial (and not tumorigenic cell) origin.

PMID- 8760063
TI  - Phorbol ester and okadaic acid regulation of Na-2Cl-K cotransport in rabbit
      tracheal epithelial cells.
AB  - We evaluated a role for protein kinase C (PKC) in the regulation of rabbit
      tracheal epithelial Na-Cl(K) cotransport. Short-term treatment with phorbol 12
      myristate 13-acetate (PMA) dose dependently increased bumetanide-sensitive Na and
      Cl efflux and elevated staurosporine- and bumetanide-sensitive Na, Cl, and K
      uptake. PMA and the alpha 2A-adrenergic agonist guanabenz both induced
      contransport with a stoichiometry of 2 Cl:1 Na and 2 Cl:1 Rb and elevated
      staurosporine-sensitive PKC activity in cytosolic and particulate fractions.
      Prolonged PMA treatment did not sustain bumetanide-sensitive 2 Cl:1 Na and 2 Cl:1
      Rb transport but did block stimulation of bumetanide-sensitive transport by PMA
      or guanabenz and elevation of PKC activity by PMA and guanabenz in a particulate
      fraction. Cells treated with okadaic acid exhibited a staurosporine- and
      bumetanide-sensitive 2 Cl:1 Na and 2 Cl:1 Rb uptake. In cultured monolayers,
      basolateral perfusion with epinephrine, isoproterenol, or PMA increased short
      circuit current (Isc). Basolateral application of bumetanide reduced elevated Isc
      to baseline levels, indicating a role for Cl secretory cells in a reconstituted
      tracheal epithelium. Pretreatment of transmonolayer cultures with PMA diminished
      the stimulatory response to epinephrine. These results indicate that, in rabbit
      tracheal epithelial cells, alpha-adrenergic stimulation activated Na-2Cl-K
      cotransport and that PKC is a critical effector in this process.

PMID- 8760064
TI  - Altered sodium current response to intracellular fatty acids in halothane
      hypersensitive skeletal muscle.
AB  - Biopsies of human skeletal muscle were analyzed by an in vitro contracture test
      (IVCT) for responsiveness to a halothane challenge: noncontracting
      (nonresponsive; IVCT-) and contracting (IVCT+). A muscle biopsy that is IVCT+
      indicates potential malignant hyperthermia (MH) susceptibility. Primary cultures
      were grown from portions of the skeletal muscle biopsies, and voltage-activated
      currents were measured by whole cell recording in the presence or absence of 2-5
      microM intracellular arachidonic or oleic acids. In untreated IVCT- cells, Na+
      currents were predominantly tetrodotoxin (TTX) insensitive, indicating that most
      of the current was carried through the embryonic SkM2 isoform of the Na+ channel.
      Inclusion of fatty acids in the recording pipette of IVCT- cells produced an
      increase in voltage-activated Na+ currents during 20 min of recording.
      Approximately 70% of currents in fatty acid-treated cells were TTX sensitive,
      indicating activation of the adult SkM1 isoform of the Na+ channel. In contrast
      to IVCT- cells, IVCT+ cells expressed Na+ currents that were predominantly TTX
      sensitive even in the absence of added fatty acid, thus showing a relatively
      large baseline functional expression of SkM1 channels. Addition of fatty acids to
      the recording pipette produced little further change in the magnitude or TTX
      sensitivity of the whole cell currents in IVCT+ cells, suggesting altered
      functional regulation of Na+ channels in MH muscle.

PMID- 8760065
TI  - Prostaglandin E2 inhibits Na-K-2Cl cotransport in medullary thick ascending limb
      cells.
AB  - Prostaglandin E2 (PGE2) is known to inhibit transepithelial Cl transport in
      medullary thick ascending limb (mTAL), but the mechanism of inhibition or the
      transport pathway affected has not been identified. We undertook this study to
      examine the effect of PGE2 on Na-K-2Cl cotransport in mouse mTAL cells in
      culture. In nanomolar concentrations, PGE2 inhibited the Na- and Cl-dependent,
      bumetanide-sensitive K influx by 45%, and this inhibition was also observed in
      the presence of 3 mM ouabain. Although PGE2 also inhibited ouabain-sensitive K
      flux, that inhibition was abolished in the presence of apical nystatin,
      suggesting that the pump inhibition was secondary to diminished Na entry into the
      cells. The effect of PGE2 was concentration dependent. Inhibition was observed at
      a concentration of < 1 nM, and half-maximal effect was observed at 2.5 nM. The
      effect of PGE2 was not mediated by an action on cytosolic Ca because cytosolic Ca
      was unchanged after the addition of PGE2. PGE2 reduced the maximal velocity for
      the cotransporter but had no effect on the affinity of the cotransporter for
      external Na, K, or Cl. Specific [3H]bumetanide binding was reduced in the
      presence of PGE2, suggesting that PGE2 affected bumetanide-sensitive K influx by
      downregulating the number of functioning Na-K-2Cl cotransporters. These results
      suggest that Na-K-2Cl cotransport in the mTAL cells may be under tonic inhibitory
      control of PGE2.

PMID- 8760066
TI  - Impaired cAMP-mediated gene expression and decreased cAMP response element
      binding protein in senescent cells.
AB  - The capacity of various growth factors to induce c-fos expression is diminished
      with senescence. Because adenosine 3',5'-cyclic monophosphate (cAMP)-mediated
      responses are also blunted with aging, we wondered whether cAMP-induced c-fos
      gene expression might be impaired with senescence. Using IMR fibroblasts, we
      found that prostaglandin E1 (PGE1) and forskolin, stimulators of cAMP
      accumulation in young and senescent cells, increased abundance of c-fos and junB
      mRNA more in young than senescent cells. The abundance of the cAMP response
      element binding protein (CREB), a transcription factor which enhances gene
      expression when phosphorylated by protein kinase A, was markedly decreased in
      both whole cell and nuclear extracts of senescent cells, in both Western blotting
      and in gel retardation assays. Also, PGE1-induced phosphorylation of CREB by
      protein kinase A was markedly attenuated in senescent cells. There is a marked
      decrement in expression of CREB with senescence, and the results suggest the
      possibility that the diminished expression of CREB may contribute to altered cAMP
      mediated regulation of gene expression with senescence.

PMID- 8760067
TI  - Human monocytes lose 5-lipoxygenase and FLAP as they mature into monocyte-derived
      macrophages in vitro.
AB  - Previous studies in mononuclear phagocytes have shown that macrophages have
      substantially greater 5-lipoxygenase activity than monocytes and that this is
      associated with greater amounts of 5-lipoxygenase and its activating protein
      (FLAP). The aim of this study was to examine the effect of mononuclear phagocyte
      maturation in vitro on 5-lipoxygenase expression. At baseline, monocytes had
      significant 5-lipoxygenase activity, but then lost all detectable 5-lipoxygenase
      activity over 7 days. Immunoblot and Northern blot analysis revealed that
      immunoreactive protein and mRNA for both 5-lipoxygenase and FLAP were
      significantly decreased over time. These studies demonstrate that in vitro
      differentiation of monocytes into a macrophage phenotype is not accompanied by
      the enhanced expression of 5-lipoxygenase and FLAP seen in macrophages derived
      from in vivo sources. In fact, baseline expression of 5-lipoxygenase and FLAP by
      monocytes is lost in vitro. These studies have clear implications for the use of
      cultured monocytes as a model of macrophages, and they also further our
      understanding of the regulation of the 5-lipoxygenase pathway.

PMID- 8760068
TI  - Functional analysis of a genetic defect of copper transport (Menkes disease) in
      different cell lines.
AB  - To define the function of the Cu-transporting ATPase in Menkes disease, Menkes
      and normal fibroblasts were incubated with 67Cu before and after brief exposure
      to -SH reagents, p-chloromercuribenzoate (PCMB) and dithiothreitol (DTT).
      Accumulation and retention were compared among these cells, BeWo cells, and rat
      C6 glioma cells similarly treated. The Michaelis constant for influx of 67Cu into
      normal and Menkes fibroblasts was practically the same (0.21 +/- 0.07 vs. 0.24 +/
      0.06 microM). The PCMB treatment stimulated 67Cu accumulation in C6 cells,
      inhibited accumulation in normal and Menkes fibroblasts, and did not affect BeWo
      cells. DTT stimulated 67Cu uptake in all cells but BeWo cells. DTT treatment
      after PCMB further enhanced 67Cu accumulation in normal fibroblasts and C6 cells
      but had no enhancing effect on Menkes fibroblasts or BeWo cells. Menkes
      fibroblasts and BeWo cells released 67Cu at rates considerably slower than normal
      fibroblasts (0.06 and 0.09 vs. 0.22%/min, respectively). The PCMB blocked 67Cu
      release from normal fibroblasts but did not affect Menkes fibroblasts or BeWo
      cells. Reverse transcription-polymerase chain reaction analysis of total RNA from
      BeWo cells failed to show a predicted 943-base pair fragment representing a
      partial transcript of the Menkes factor. The fragment was present in extracts
      from normal fibroblasts. We conclude that the mechanism underlying Cu homeostasis
      varies among different cell types. As exemplified by BeWo and Menkes cells,
      failure to efflux Cu ions may be linked with the failure to express a functional
      Cu-transporting ATPase, namely, the Menkes protein.

PMID- 8760069
TI  - Enhanced NO production during Mg deficiency and its role in mediating red blood
      cell glutathione loss.
AB  - The effect of dietary Mg deficiency on nitric oxide (NO) production and its role
      in mediating oxidative depletion of red blood cell (RBC) glutathione in rats were
      investigated. Male Sprague-Dawley rats were placed on Mg-deficient or Mg
      sufficient diets for up to 3 wk. Plasma nitrate plus nitrite levels, determined
      by the Escherichia coli reductase/Griess reagent procedures, increased 1.7-fold
      during the 1st wk and increased 2- to 2.4-fold during the 2nd and 3rd wk on the
      Mg-deficient diet. In association, substantial losses (approximately 50%) of RBC
      glutathione occurred during the 2nd and 3rd wk. Administration of the NO
      synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in drinking water
      (0.5 mg/ml) effectively blunted the increases in plasma nitrate/nitrite during Mg
      deficiency. Concomitantly, losses of RBC glutathione exhibited by Mg-deficient
      rats were significantly attenuated. Packed RBCs, obtained from Mg-deficient but
      not from Mg-sufficient animals, displayed a prominent nitrosyl hemoglobin signal
      detected by electron spin resonance spectroscopy; the signals of the samples from
      the L-NAME-treated Mg-deficient rats were greatly reduced. With isolated RBCs,
      losses of the glutathione could be induced directly by peroxynitrite or 3
      morpholinosydnonimine, which generates NO + .O2-, but not by NO (from sodium
      nitroprusside) alone, in a concentration-dependent manner. The results clearly
      indicate that NO overproduction occurs and participates in RBC glutathione loss
      during Mg deficiency. Because neutrophil activation also occurs, we suggest that
      NO might interact with superoxide anions to form peroxynitrite, which then
      directly oxidizes RBC glutathione.

PMID- 8760070
TI  - Effect of ablation of phospholamban on dynamics of cardiac myocyte contraction
      and intracellular Ca2+.
AB  - We compared mechanical activity and Ca2+ transients of ventricular myocytes
      isolated from wild-type and phospholamban (PLB)-deficient mouse hearts in control
      conditions and during beta-adrenergic stimulation. Compared with wild-type
      controls, cells isolated from PLB-deficient mouse hearts showed 1) a 2-fold
      increase in extent of cell shortening, 2) a 3-fold increase in maximal shortening
      velocity, and 3) a 3.4-fold increase in maximal relengthening velocity. PLB
      deficient myocytes also demonstrated significant increases in the peak amplitude
      of the fura 2 fluorescence ratio and the rates of rising and falling phases of
      the Ca2+ transient. The fura 2 diastolic ratios were similar in both groups,
      suggesting no change in intracellular Ca2+ during diastole. In PLB-deficient
      myocytes, 0.05 microM isoproterenol induced an increase in the twitch amplitude
      by 152 +/- 11% (n = 6) compared with 290 +/- 31% (n = 6) in wild-type cells.
      Maximal shortening velocity was increased by 183 +/- 10% (n = 6) in PLB-deficient
      myocytes, compared with 398 +/- 62% (n = 6) in wild-type cells. The isoproterenol
      induced increase in maximum relengthening velocity was increased by 168 +/- 8% (n
      = 6) in PLB-deficient cells compared with 445 +/- 71% (n = 6) in wild-type
      myocytes. In both groups, these changes in contractile parameters were
      accompanied by changes in the Ca2+ transient. Our results indicate that
      phosphorylation of sites other than PLB may play an important role in regulation
      of contraction-relaxation dynamics of heart cells responding to beta-adrenergic
      stimulation.

PMID- 8760071
TI  - Action of protein kinase C in endothelin-induced contractions in rat aortic
      rings.
AB  - Endothelin (ET) is a potent vasoconstrictor peptide that induces
      characteristically long-lasting contractions. We used both intact and endothelium
      denuded rat aortic rings to investigate the role of protein kinase C (PKC) in ET
      induced contractions. ET (10(-9) M) and phorbol 12,13-dibutyrate (PDBu), a PKC
      activator, produced a gradual and sustained contraction of greater magnitude in
      denuded aortic rings than in intact rings. When aortic rings were pretreated with
      graded concentrations of different PKC inhibitors, inhibition of ET-induced
      contractions began at 10(-9)M and was nearly complete at 10(-3)M, and the
      reduction was greater in intact than in denuded rings. Pretreatment of aortic
      rings with PDBu or NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of
      nitric oxide synthase, potentiated ET-induced contractions. PKC enzyme assay
      showed activation of PKC in aortic rings that were treated with either ET or
      PDBu, inhibition after pretreatment with PKC inhibitors, and no change with 4
      alpha-phorbol 12,13-didecanoate (PDD), an inactive phorbol ester. ET
      significantly increased nitrate and nitrite production, which was further
      increased by pretreatment with PKC inhibitors. PDBu prevented ET-induced
      nitrate/nitrite production, and PDD had no effect. These results strongly suggest
      that PKC mediates, in part, ET-induced contractions in rat aortic rings and that
      an intact endothelium is required for maximum inhibition by PKC inhibitors
      because PKC stimulated by ET inhibits nitric oxide release.

PMID- 8760072
TI  - Mechanism of nonlinear responses of taste cells to mixed tastes.
AB  - Coupling between ionic flows through different kinds of channels affects
      essentially the responses of multisensitive taste cells to single- and mixed
      taste stimuli. The mechanism of taste transduction is studied by using a
      realistic model of the multisensitive cells of the rat. The transduction pathways
      considered are amiloride-sensitive Na+ channels for NaCl and HCl and adenosine
      3',5'-cyclic monophosphate-mediating K+ channels for sucrose. Contributions of
      paracellular pathways and taste-insensitive ionic channels are also studied. The
      calculated responses of various multisensitive cells induced by single stimuli of
      NaCl, HCl, or sucrose reproduce experimentally observed responses as well. The
      two main conclusions are as follows. 1) Whether the response of a cell to a
      binary mixture becomes synergetic or antagonistic can be estimated from the
      individual responses of the cell to each component of the mixture. 2) Whether the
      response is enhanced or suppressed by addition of a new taste to the original
      taste can be determined, for most receptive cells, from a viewpoint of linear
      superposition of the individual responses.

PMID- 8760073
TI  - Aldosterone regulation of sodium channel gamma-subunit mRNA in cortical
      collecting duct cells.
AB  - Specific regulatory mechanisms of aldosterone-stimulated Na+ reabsorption through
      the apical amiloride-sensitive channel are unknown. In this study, we examined
      the effects of aldosterone on Na+ channel gamma-subunit mRNA levels in cultured
      rabbit cortical collecting duct cells. With the use of reverse transcriptase
      polymerase chain reaction (RT-PCR) with RNA isolated from aldosterone-treated
      cells and degenerate primers, a 446-base pair (bp) PCR product was amplified and
      further characterized by nested PCR and sequencing. The nested PCR yielded a
      predicted 164-bp product. Sequencing of the 446-bp PCR product revealed 83%
      nucleotide and 91% amino acid identity to the rat colonic Na+ channel gamma
      subunit. The relative abundance of Na+ channel mRNA was determined by
      quantitative PCR after a 24-h aldosterone treatment. The results demonstrate that
      Na+ channel gamma-subunit mRNA levels were significantly higher (2.6 +/- 0.42) in
      aldosterone-treated cultures vs. the controls. This increase, however, is less
      than the aldosterone-induced increase (3.2 +/- 2.0) in the amiloride-sensitive
      short-circuit current. These results indicate that Na+ channel gamma-subunit mRNA
      levels are increased by aldosterone and that this increase is likely to be
      responsible, at least in part, for the aldosterone-induced Na+ current in the
      kidney.

PMID- 8760074
TI  - Protein kinase A activation is required for IL-1-induced nitric oxide production
      by cardiac myocytes.
AB  - We have previously reported that interleukin-1 beta (IL-1) alone induced the
      transcription of inducible nitric oxide synthase (iNOS) mRNA and nitric oxide
      (NO) production by isolated neonatal rat cardiac myocytes (CM). The present
      studies were undertaken to explore the signal transduction pathways involved in
      IL-1-induced NO production by CM. The addition of IL-1 to CM resulted in a peak
      rise in both adenosine 3',5'-cyclic monophosphate (cAMP) and protein kinase A
      (PKA) activities by 10 min followed by rapid declines and return to basal levels
      within 60 min. The PKA inhibitor KT-5720 completely blocked NO-2 production by IL
      1-stimulated CM (P < 0.01; n = 12). The protein kinase C (PKC) inhibitor,
      calphostin C, had no effect on NO2- production by IL-1 stimulated CM [P = not
      significant (NS); n = 12]. The addition of PKA+cAMP to cytosols derived from IL-1
      treated CM did not directly enhance iNOS enzyme activity (P = NS; n = 3). CM
      treated with IL-1 alone stained positively for iNOS protein by
      immunohistochemistry. iNOS staining was absent in CM treated with IL-1+KT-5720.
      KT-5720 resulted in an earlier disappearance of iNOS mRNA from IL-1-treated CM,
      as detected by semiquantitative reverse transcriptase-polymerase chain reaction.
      We report for the first time that PKA (but not PKC) activation is required for IL
      1-induced NO production by CM.

PMID- 8760075
TI  - Compartmentalization of protein traffic in insulin-sensitive cells.
AB  - Insulin-sensitive cells, adipocytes and myocytes, translocate a number of
      intracellular proteins to the cell surface in response to insulin. Among these
      proteins are glucose transporters 1 and 4 (GLUT-1 and GLUT-4, respectively),
      receptors for insulin-like growth factor II (IGF-II)/mannose 6-phosphate (Man-6
      P) and transferrin, the aminopeptidase gp 160, caveolin, and a few others. In the
      case of insulin-activated glucose transport, this translocation has been proven
      to be the major, if not the only regulatory mechanism of this process. It seems
      likely that the cell surface recruitment of the IGF-II/Man-6-P and transferrin
      receptors also serves the nutritional needs of cells, whereas the physiological
      role of the aminopeptidase gp160 remains uncertain. Analysis of the
      compartmentalization and trafficking pathways of translocatable proteins in fat
      cells identified more than one population of recycling vesicles, although all
      have identical sedimentation coefficients and buoyant densities in vitro. GLUT-4
      containing vesicles include essentially all the intracellular GLUT-4, gp160, and
      the acutely recycling populations of receptors for IGF-II/Man-6-P and
      transferrin. Besides these proteins, which can be considered as vesicle "cargo",
      GLUT-4-containing vesicles have other components, like secretory carrier
      associated membrane proteins (SCAMP), Rab(s), and vesicle-associated membrane
      protein (VAMP)/cellubrevin, which are ubiquitous to secretory vesicles and
      granules from different tissues. GLUT-1 and caveolin are excluded from GLUT-4
      containing vesicles and form different vesicular populations of unknown
      polypeptide composition. In skeletal muscle, two independent populations of GLUT
      4-containing vesicles are found, insulin sensitive and exercise sensitive, which
      explains the additive effect of insulin and exercise on glucose uptake. Both
      vesicular populations are similar to each other and to analogous vesicles in fat
      cells.

PMID- 8760076
TI  - T3 potentiates the adrenergic stimulation of type II 5'-deiodinase activity in
      cultured rat brown adipocytes.
AB  - Iodothyronine type II 5'-deiodinase (5'D-II) activities were studied in cultures
      of rat brown adipocytes. In the presence of serum, the adrenergically stimulated
      5'D-II activities were very low. In the absence of serum, adenosine 3',5'-cyclic
      monophosphate (cAMP) analogues stimulated 5'D-II activity. Thyroxine (T4)
      inhibited these increases. Norepinephrine slightly increased 5'D-II activity in
      hypothyroid conditions, but 3,5,3'-triiodothyronine (T3) strongly potentiated the
      adrenergic stimulation of 5'D-II (20-fold). T3 amplification of the adrenergic
      stimulation was via beta-adrenergic receptors, specifically mimicked by beta3
      agonists, but it was not observed using cAMP analogues. The stimulatory effect of
      T3 predominated over the inhibitory action of T4, increased with exposure to T3,
      and required de novo protein synthesis. The half-life of 5'D-II was 30 min,
      suggesting that stabilization of 5'D-II did not occur. The effect was only
      observed in differentiated adipocytes. Retinoic acid has similar although smaller
      effects than T3. In conclusion, the presence of T3 is required and strongly
      potentiates the noradrenergic stimulation of 5'D-II activity in rat brown
      adipocytes.

PMID- 8760077
TI  - Galanin gene expression in radiothyroidectomy-induced thyrotroph adenomas.
AB  - Galanin gene expression is markedly increased in the anterior pituitary glands of
      estrogen-treated rats (lactotroph hyperplasia) as well as human growth hormone
      releasing hormone transgenic mice (somatotroph hyperplasia). The objective of
      this study was to examine galanin in a mouse model of thyrotroph adenoma
      formation. Male mice were radiothyroidectomized by use of iodine-131 (131I), and
      galanin peptide levels were assessed in the hypothalamic-pituitary axis.
      Immunoreactive galanin concentrations in the anterior pituitaries of 131I-treated
      mice were decreased 80% at 3, 6, 9, and 12 mo after radiothyroidectomy. Galanin
      peptide levels in the hypothalamus were decreased 20-25% at these times.
      Treatment with either estradiol or 3,3',5-triiodo-L-thyronine increased galanin
      peptide concentrations in the anterior pituitaries of 131I-treated mice, but
      neither treatment restored galanin concentrations. Galanin mRNA levels were
      decreased > 80% 1 yr after radiothyroidectomy. We conclude that, unlike animal
      models of lactotroph and somatotroph hyperplasia, galanin gene expression is
      suppressed throughout the development of thyrotroph adenomas, suggesting that
      galanin does not have a stimulatory role in the proliferation of thyrotrophs.
      Moreover, these data show that thyroid hormones are important positive regulators
      of galanin gene expression in the mouse and that estrogen may stimulate galanin
      gene expression in the absence of thyroid hormones.

PMID- 8760078
TI  - Creatine ingestion favorably affects performance and muscle metabolism during
      maximal exercise in humans.
AB  - Nine male subjects performed two bouts of 30-s maximal isokinetic cycling before
      and after ingestion of 20 g creatine (Cr) monohydrate/day for 5 days. Cr
      ingestion produced a 23.1 +/- 4.7 mmol/kg dry matter increase in the muscle total
      creatine (TCr) concentration. Total work production during bouts 1 and 2
      increased by approximately 4%, and the cumulative increases in both peak and
      total work production over the two exercise bouts were positively correlated with
      the increase in muscle TCr. Cumulative loss of ATP was 30.7 +/- 12.2% less after
      Cr ingestion, despite the increase in work production. Resting phosphocreatine
      (PCr) increased in type I and II fibers. Changes in PCr before exercise bouts 1
      and 2 in type II fibers were positively correlated with changes in PCr
      degradation during exercise in this fiber type and changes in total work
      production. The results suggest that improvements in performance were mediated
      via improved ATP resynthesis as a consequence of increased PCr availability in
      type II fibers.

PMID- 8760079
TI  - Metabolic response of type I and II muscle fibers during repeated bouts of
      maximal exercise in humans.
AB  - Nine male subjects performed two bouts of 30-s maximal isokinetic cycling. Each
      bout of exercise was performed at 80 revolutions/min and was separated by 4 min
      of recovery. Mixed-muscle phosphocreatine (PCr) resynthesis during recovery (88.1
      +/- 6.1%) was positively correlated with the restoration of total work production
      during bout 2 (r = 0.80, P < 0.05). During bout 1, ATP and PCr utilization were
      greater in type II compared with type I fibers (P < 0.01 and P < 0.05,
      respectively). The subsequent 4-min period of recovery was insufficient to allow
      total restoration of ATP and PCr in type II fibers, but restoration of ATP and
      PCr in type I fibers was almost complete. During the second bout of exercise, ATP
      and PCr utilization were reduced in type II fibers (P < 0.01), without a
      corresponding change in type I fibers, and performance was also significantly
      reduced. The reduction in work capacity observed during bout 2 may have been
      related to a slower resynthesis, and consequently a reduced availability, of ATP
      and PCr in type II fibers.

PMID- 8760080
TI  - Adipose tissue stearoyl-CoA desaturase mRNA is increased by obesity and decreased
      by polyunsaturated fatty acids.
AB  - Stearoyl-CoA desaturase (SCD) is a key regulatory enzyme in the synthesis of
      unsaturated fatty acids. Although regulation of hepatic SCD by obesity and
      polyunsaturated fatty acids (PUFA) has been well investigated, no studies have
      addressed whether similar regulation occurs in adipose tissue. We addressed these
      questions by feeding control (12% corn oil) and high-PUFA (48% corn oil) diets to
      lean and obese Zucker rats and analyzing SCD mRNA levels in adipose tissue and
      liver. We report that SCD mRNA content was dramatically elevated in adipose
      tissue of obese vs. lean rats on both diets and was significantly decreased by
      PUFA in both genotypes. Interestingly, we demonstrate that SCD expression was
      directly downregulated in a dose dependent manner by PUFA in 3T3-L1 adipocytes.
      We conclude that 1) obese Zucker rats overexpress the SCD gene in both liver and
      adipose tissue and 2) PUFA directly suppress SCD expression in adipocytes.
      Further studies will elucidate the mechanisms responsible for obesity- and PUFA
      mediated regulation of SCD in adipose cells.

PMID- 8760081
TI  - Reciprocal GLUT-1 and GLUT-4 expression and glucose transport in denervated
      muscles.
AB  - We investigated in 3-day-denervated muscles 1) the expression of GLUT-1 in
      perineurial sheaths (PNS) and muscle, 2) the muscle fiber-specific changes in
      GLUT-1 and GLUT-4, and 3) changes in basal and insulin-stimulated 3-O
      methylglucose transport. GLUT-1 was increased in both the PNS (P < 0.05) and in
      the muscle membranes (P < 0.05). GLUT-1 and GLUT-4 concentrations were changed
      reciprocally, in a fiber-dependent fashion [GLUT-1: red gastrocnemius (RG), +31%;
      white gastrocnemius (WG), +10%; GLUT-4: RG, -53%; WG, -16%]. Basal glucose
      transport was increased (P < 0.05), and this increase was correlated with the
      oxidative nature of the muscles (r = 0.97). Insulin-stimulated glucose transport
      was decreased in denervated muscles (P < 0.05). This was also related to the
      oxidative nature of the muscles (r = -0.88). The increase in basal glucose
      transport was correlated with the loss of insulin-stimulated transport (r =
      0.95). Thus the increase in GLUT-1 compensates for the loss of GLUT-4, resulting
      in a 56% regain of the reduced insulin-stimulated glucose transport.

PMID- 8760082
TI  - Kinetic aspects of acetate metabolism in healthy humans using [1-13C] acetate.
AB  - Acetate metabolism in humans is not well known. Kinetic aspects of acetate were
      investigated in the postabsorptive state on healthy subjects. In a first study,
      six subjects were infused with a primed constant infusion of [1-13C]acetate for 3
      h and a prime of NaH13CO3. No difference was found between arterialized and
      venous tracer enrichments from the arm, although arterialized acetate
      concentrations were higher (74 +/- 12 vs. 59 +/- 14 mumol/l, P < 0.05),
      suggesting that the hand muscles used but did not produce acetate in the
      postabsorptive state. Total body flux of acetate was 8.4 +/- 0.6 mumol.kg-1.min
      1, of which 69 +/- 5% was oxidized. Acetate contributed to 6.5 +/- 0.4% of the
      basal energy expenditure. In a second study, five volunteers were submitted to a
      gastric infusion for 3 h followed by an intravenous infusion of [1-13C]acetate
      for 3 h. Higher fluxes were observed with the tracer gastric infusion, and the
      first-pass removal of acetate within the splanchnic bed was 60 +/- 7%. Acetate
      contributes significantly to the energy supply of the body. It is mainly used by
      the liver when produced in the gut.

PMID- 8760083
TI  - Involvement of G proteins in the effect of carbachol and cholecystokinin in rat
      pancreatic islets.
AB  - Phospholipase C is involved in the insulinotropic effect of carbachol (CCh) and
      cholecystokinin octapeptide (CCK-8). The involvement of the type of G protein was
      investigated in rat pancreatic islets. Guanosine 5'-O-(3-thiotriphosphate) (GTP
      gamma S; a nonhydrolyzable GTP analogue) increased insulin release in
      electrically permeabilized islets. Both CCh and CCK-8 increased the GTP gamma S
      effect indicative of an involvement of G proteins. Pretreatment of the islets
      with pertussis toxin (PT) impaired the CCh-induced insulin secretion in the
      presence of 3.0 mM glucose and inhibited the stimulatory CCh effect on inositol
      1,4,5-trisphosphate (IP3) levels at low and high glucose. In contrast to CCh, the
      CCK-8 effect on both insulin release and IP3 levels of islets was not modified by
      a PT pretreatment at various glucose concentrations. Two types of experiments
      indicate the type of G protein involved: first, long-term agonistic stimulation
      by either CCh or CCK-8 led to a downregulation of alpha o and alpha q/11,
      respectively; second, introduction of specific anti-alpha o or -alpha q/11
      antibodies into electrically permeabilized islets nearly completely abolished the
      effects of CCh and CCK-8, respectively. The data indicate that both CCh and CCK-8
      act as insulinotropic agents via the phospholipase C system; in the effect of CCh
      the PT-sensitive alpha o and in the effect of CCK-8 the PT-insensitive alpha q/11
      is involved.

PMID- 8760084
TI  - Kinetic analysis of receptor-mediated endocytosis of G-CSF derivative,
      nartograstim, in rat bone marrow cells.
AB  - To elucidate the mechanism of the receptor-mediated clearance of granulocyte
      colony-stimulating factor (G-CSF), we performed kinetic analyses of the receptor
      mediated endocytosis (RME) processes using a human G-CSF derivative, nartograstim
      (NTG), and isolated rat bone marrow cells. The first-order rate constants
      involved in RME processes were obtained by computerized model fitting of the time
      courses of the ligand-receptor complex on both the cell surface and in the cell
      interior and the degradation products in the medium in the pulse-chase
      experiment. They were also calculated based on a kinetic model involving the
      ligand concentration dependence of the initial binding rate, the steady-state
      degradation rate, and the steady-state amounts of ligand on both the cell surface
      and in the interior. The rate constants for the RME processes after receptor
      binding determined in the different experiments were similar, that is, the half
      times for the dissociation, internalization, and degradation of the ligand
      receptor complex were 770, 10-30, and 20 min, respectively. However, the
      association constant obtained by measuring the initial binding was fivefold
      greater than that calculated under steady-state conditions. These kinetic
      analyses support the hypothesis that the internalization of the receptor may be
      accelerated by ligand binding, causing downregulation of the receptor on the cell
      surface. These overall kinetic analyses based on steady-state and non-steady
      state data of the RME processes clarify the dynamics of the interaction between
      NTG and its receptor.

PMID- 8760085
TI  - Role for GTP in glucose-induced phospholipase C activation in pancreatic islets.
AB  - We have previously demonstrated a permissive role for GTP in insulin secretion;
      in the current studies, we examined the effect of GTP on phospholipase C (PLC)
      activation to explore one possible mechanism for that observation. In rat islets
      preexposed to the GTP synthesis inhibitors mycophenolic acid (MPA) or mizoribine
      (MZ), PLC activation induced by 16.7 mM glucose (or by 20 mM alpha-ketoisocaproic
      acid) was inhibited 63% without altering the labeling of phosphoinositide
      substrates. Provision of guanine, which normalizes islet GTP content and insulin
      release, prevented the inhibition of PLC by MPA. Glucose-induced phosphoinositide
      hydrolysis was blocked by removal of extracellular Ca2+ or by diazoxide. PLC
      induced directly by Ca2+ influx (i.e., 40 mM K+) was reduced 42% in MPA
      pretreated islets but without inhibition of the concomitant insulin release.
      These data indicate that glucose-induced PLC activation largely reflects Ca2+
      entry and demonstrate (for the first time in intact cells) that adequate GTP is
      necessary for glucose (and Ca(2+)-)-induced PLC activation but not for maximal
      Ca(2+)-induced exocytosis.

PMID- 8760086
TI  - Perfused skeletal muscle contraction and metabolism improved by angiotensin II
      mediated vasoconstriction.
AB  - In the present study, the effects of angiotensin II (ANG II) on tension
      development and associated metabolism during twitch and tetanic stimulation via
      the sciatic nerve of the gastrocnemius-plantaris-soleus muscle group of the
      perfused rat hindlimb were investigated. Rat hindlimbs were perfused at constant
      flow with an erythrocyte-containing medium equilibrated with 95% air-5% CO2 at 37
      degrees C, and determinations of oxygen and glucose uptake, lactate and glycerol
      release, and 2-deoxy-D-[1-3H]glucose uptake (Rg') into individual muscles were
      carried out. ANG II (1 nM) infusion alone caused vasoconstriction with increased
      oxygen (55%) and glucose (98%) uptake and lactate (37%) and glycerol (64%)
      release. ANG II infusion during muscle contraction gave less vasoconstriction but
      increased the tension development during tetanic stimulation by 80% and increased
      the contraction-induced oxygen uptake and Rg' by plantaris and gastrocnemius red
      and white muscles. These effects of ANG II may have been due to increased
      nutritive flow to contracting muscles or to redirection of flow from
      noncontracting and type I fiber muscles to the type II fiber contracting muscles
      in the hindlimb. The results indicate that the regulation of flow by the
      vasculature is an important regulator of muscle contraction and metabolism.

PMID- 8760087
TI  - Expression of AT1A and AT1B angiotensin II receptor messenger RNA in forebrain of
      2-wk-old rats.
AB  - The gene expression of angiotensin II receptor subtypes AT1A and AT1B was
      localized in the forebrain of 2-wk-old rats by in situ hybridization
      histochemistry and compared with [125I]Sar1-angiotensin II binding patterns. AT1A
      receptor mRNA was expressed in circumventricular organs, in hypothalamic nuclei
      like the paraventricular nucleus, in the lateral olfactory tract, in the
      basolateral amygdaloid and anterior olfactory nuclei, and in the piriform cortex.
      No AT1B receptor mRNA was detected in these areas. AT1A and AT1B receptor mRNA
      was detected in the hippocampus, cingulate cortex, and choroid plexus. No
      forebrain area studied expressed AT1B receptor mRNA exclusively. Most often, a
      good match for receptor mRNA and binding was found. In some areas, apparent
      mismatches suggested receptor formation elsewhere (median eminence) or receptor
      presence in local neuronal circuits (hippocampus, cingulate, and piriform
      cortex). Our results support the hypothesis that AT1A receptors are involved in
      the classical central functions of angiotensin II. Both AT1A and AT1B receptors
      may play roles in cortical and limbic system function, particularly early in
      development.

PMID- 8760088
TI  - Role of nitric oxide resistance in erythropoietin-induced hypertension in rats
      with chronic renal failure.
AB  - We studied the mechanism of erythropoietin (EPO)-induced hypertension (HTN) in
      rats with chronic renal failure (CRF). After partial nephrectomy, rats were
      randomized into four groups. Group A received EPO, 150 U/kg, two times weekly for
      6 wk to prevent anemia; group B received placebo injections and became anemic;
      group C received EPO but was kept anemic by dietary iron deficiency; and group D
      received placebo and regular transfusions to match hematocrit (Hct) in group A.
      Blood pressure (BP), Hct, platelet cytosolic calcium ([Ca2+]i) and magnesium
      concentration, and pressor and vasodilatory responses were determined. By design,
      Hct in groups A and D were comparable and significantly greater (P < 0.01) than
      in groups B and C. Despite divergent Hct values, the EPO-treated groups A and C
      showed a significant rise in BP compared with the placebo-treated groups B and D.
      HTN occurred whether EPO therapy was begun immediately or 4 wk after nephrectomy.
      EPO therapy augmented the elevation of basal [Ca2+]i and restored the defective
      thrombin-mediated rise of platelet [Ca2+]i in CRF animals. EPO therapy did not
      alter caudal artery contraction in response to either 68 mM K(+)-induced
      depolarization, angiotensin II or alpha 1-agonist, methoxamine in vitro, or the
      pressor response to angiotensin II in vivo. However, EPO therapy impaired the
      hypotensive response to nitric oxide (NO) donors, sodium nitroprusside and S
      nitroso-N-acetyl-D,L-penicillamine, and reversed the CRF-induced upregulation of
      guanosine 3',5'-cyclic monophosphate production by thoracic aorta in vitro. Thus
      EPO-induced HTN in CRF rats is Hct independent and is associated with and perhaps
      causally related to increased basal and stimulated [Ca2+]i and impaired
      vasodilatory response to NO.

PMID- 8760089
TI  - Effects of pulsatile delivery of basal growth hormone on lipolysis in humans.
AB  - Growth hormone (GH) excess stimulates lipolysis, but its role in the hierarchy of
      lipolysis regulation is not clear. We studied whether pulsatile GH delivery is
      required for its lipolytic effect. With use of the pancreatic clamp, eight
      subjects were randomized to three protocols: protocol A, GH deficiency; protocol
      B, constant GH infusion; protocol C, pulsatile GH delivery (same total GH as
      protocol B). Pulsatile GH was given in four consecutive bursts, with symmetric
      peak width (60 min), amplitude of 10.7 (men) and 15 (women) ng.kg-1.min-1, and
      peak width at half-height of 15 min. Palmitate flux (PF) was measured at baseline
      and in the last hour of each study with [3H]palmitate. GH (ng/ml) decreased from
      approximately 3.5 to 2.0 in protocol A (P < 0.05), it remained between 3.2 and
      4.0 in protocol B (P < 0.05), but in protocol C it fluctuated between
      approximately 2.7 and approximately 5.0 (P < 0.05). Palmitate concentration (in
      mumol/l) was approximately 150 at baseline; it did not change in protocols A and
      B (137 +/- 17 and 136 +/- 12, respectively) but increased to 198 +/- 16 (P <
      0.05) in protocol C. PF (mumol.kg-1.min-1) was approximately 2.7 at baseline and
      did not change in protocol B (2.4 +/- 0.2); it decreased to 2.2 +/- 0.1 in
      protocol A (P < 0.05); it increased to 3.1 +/- 0.3 (P < 0.05) in protocol C.
      These experiments provide evidence that pulsatile secretion of GH is required for
      its lipolytic effect.

PMID- 8760090
TI  - Direct effects of catecholamines on hepatic glucose production in conscious dog
      are due to glycogenolysis.
AB  - The effects of catecholamines (CATS) infused into the hepatic portal vein were
      studied in ten 18-h-fasted conscious dogs. Glucose production (GP) and
      gluconeogenesis (GNG) were assessed using tracer ([3H]glucose, [14C]alanine) and
      arteriovenous difference techniques. Each experiment consisted of a 100-min
      equilibration, a 40-min basal, and two 90-min test periods. A pancreatic clamp
      (somatostatin + basal portal insulin and glucagon) was used to fix insulin and
      glucagon at basal levels. Propranolol (1 microgram.kg-1.min-1) and phentolamine
      (2 micrograms.kg-1.min-1) were infused intraportally during both test periods of
      the blockade group while a carrier solution was infused in the control group.
      Norepinephrine (NE; 100 ng.kg-1.min-1) and epinephrine (Epi; 40 ng.kg-1.min-1)
      were infused intraportally during the second test period of both protocols.
      Portal NE (70 +/- 46 to 8,404 +/- 674 and 162 +/- 57 to 6,530 +/- 624 pg/ml,
      respectively) and portal Epi (21 +/- 11 to 3,587 +/- 309 and 29 +/- 6 to 2,989 +/
      406 pg/ml, respectively) rose in the control and adrenergic blockade groups,
      respectively. The increases in arterial NE and Epi were modest in both groups.
      Intraportal infusion of CATS increased GP from 2.1 +/- 0.2 to 6.2 +/- 1.0 mg.kg
      1.min-1 in the control group but did not change it (2.7 +/- 0.4 to 2.7 +/- 0.3
      mg.kg-1.min-1) in the blockade group. Portal CATS had no effect on GNG in the
      presence or absence of adrenergic blockade (GNG rose from 0.7 +/- 0.2 to 0.9 +/-
      0.2 and 0.8 +/- 0.2 to 1.0 +/- 0.2 mg.kg-1.min-1 in the control and blockade
      groups, respectively). In conclusion, portal infusion of catecholamines
      significantly augmented GP by selectively stimulating glycogenolysis. The
      increase in hepatic GP could be completely inhibited by intraportal adrenergic
      blockade.

PMID- 8760091
TI  - Microdialysis measurements in skin: evidence for significant lactate release in
      healthy humans.
AB  - To assess net lactate release from dermal skin, seven lean, healthy men were
      studied after overnight fasting. Two microdialysis catheters were inserted in the
      upper dermal tissue, as ensured by ultrasound scanning, in the periumbilical
      area. Each catheter was calibrated in situ to get an estimate of the lactate
      concentration in interstitial fluid (1,001 +/- 24 mumol/l), which in turn enabled
      calculation of the local capillary-venous lactate concentration (963 +/- 25
      mumol/l). Concomitantly, arterialized venous plasma lactate (673 +/- 32 mumol/l),
      blood hematocrit (43 +/- 1%), and skin blood flow (3.8 +/- 0.9 ml.100 g-1.min-1)
      as measured by 133Xe clearance were determined, and dermal apparent lactate
      release (570 +/- 89 nmol.100 g-1.min-1) was estimated according to the Fick
      principle. During an oral glucose tolerance test (OGTT, 75 g), the dermal
      interstitial-arterial lactate difference decreased significantly to reach a nadir
      at 60 min. Moreover, no significant increase in skin blood flow was seen during
      the OGTT. In conclusion, we found a significant net lactate release from
      abdominal dermal skin after overnight fasting, whereas no significant increase
      was observed during an OGTT.

PMID- 8760092
TI  - Role of the lactate transporter (MCT1) in skeletal muscles.
AB  - We used an antibody, constructed against the monocarboxylate transporter 1 (MCT1)
      protein (L. Carpenter, R. C. Poole, and A. P. Halestrap. Biochim. Biophys. Acta
      1279: 157-165, 1996), to study the expression and role of MCT1 in rat skeletal
      muscles. MCT1 was higher in red than in white muscles (P < 0.05) and was highly
      correlated with the oxidative fiber content (%slow-twitch oxidative + %fast
      twitch oxidative glycolytic) of skeletal muscles (r = 0.91). MCT1 was highly
      related to lactate uptake in skeletal muscles (r = 0.90). Total lactate
      dehydrogenase (LDH) activity, an index of glycolysis, was negatively correlated
      with MCT1 in rat muscles (r = -0.80). MCT1 was also strongly correlated with the
      heart-type forms of LDH (LDH-1 vs. MCT1, r = 0.83; LDH-2 vs. MCT1, r = 0.89).
      There was no relationship between MCT1 and the muscle form of LDH (LDH-5; P >
      0.05). MCT1 was highly correlated with citrate synthase activity, a marker of the
      oxidative capacity of muscle (r = 0.82). Therefore, MCT1 may have kinetics that
      favor the uptake of L-lactate into the muscle cell for oxidative metabolism, and
      MCT1 may be coordinately expressed with the heart forms of LDH and enzymes of
      oxidative metabolism.

PMID- 8760093
TI  - Dexamethasone rapidly increases hypothalamic neuropeptide Y secretion in
      adrenalectomized ob/ob mice.
AB  - A single intracerebroventricular injection of dexamethasone (DEX) rapidly (within
      30 min) suppresses brown adipose tissue thermogenesis and increases plasma
      insulin concentrations in adrenal-ectomized (ADX) ob/ob mice but not in ADX lean
      mice. Intracerebroventricular neuropeptide Y (NPY) administered
      intracerebroventricularly causes these same metabolic changes within 30 min in
      both ob/ob and lean ADX mice. We therefore hypothesized that DEX exerts these
      rapid-onset metabolic actions in ob/ob mice via a phenotype-specific enhancement
      of NPY secretion within the central nervous system. In support of this
      hypothesis, DEX (a type II glucocorticoid receptor agonist) administered
      intracerebroventricularly selectively lowered NPY concentrations in the whole
      hypothalamus of ADX ob/ob mice by 35% and in the arcuate nucleus region by
      approximately 70% within 30 min but not in the brain stem or hippocampus or in
      any of these regions of lean mice. DEX also functioned in vitro to enhance
      depolarization-dependent release of NPY from hypothalamic blocks of ADX ob/ob
      mice but not of ADX lean mice. Thus DEX acts in the hypothalamus of ob/ob mice in
      a phenotype-specific manner to evoke rapid transport of NPY from cell bodies
      within the arcuate nucleus to terminal regions including the dorsomedial and
      ventromedial hypothalamic regions for release.

PMID- 8760094
TI  - Response of phosphoenolpyruvate cycle activity to fasting and to hyperinsulinemia
      in human subjects.
AB  - We have used a new isotopic tracer technique to investigate the physiological
      role of the phosphoenolpyruvate (PEP) cycle in metabolic adaptation to fasting
      and to hyperinsulinemia. The forward direction of the PEP cycle is the conversion
      of oxaloacetate (OAA) to PEP, and the net flux of the cycle is the rate at which
      PEP from OAA goes on to form glucose or glycogen, as opposed to being recycled to
      pyruvate and then OAA. Normal volunteers (n = 6) were studied after an overnight
      fast and then again after 3 days of fasting, and five additional subjects were
      studied during a hyperinsulinemic clamp (insulin concentration = 568 +/- 25
      microU/ml, glucose infusion = 14.2 +/- 0.55 mg.kg-1.min-1). After an overnight
      fast, 35.4 +/- 6.7% of PEP from OAA was recycled to pyruvate-lactate. Short-term
      fasting caused a significant increase in the conversion of OAA to PEP and also a
      drop in the percentage of PEP from OAA that went to pyruvate-lactate to 15.2 +/-
      4.0%. The principal response to hyperinsulinemia was a decrease in the recycling
      of OAA to lactate, because there was no significant change in the conversion of
      OAA to PEP. We conclude that changes in both directions of the PEP cycle are
      important in regulating gluconeogenic-glyconeogenic flux.

PMID- 8760095
TI  - Effects of circulating IGF-I on glucose and amino acid kinetics in the ovine
      fetus.
AB  - To investigate the role of insulin-like growth factor I (IGF-I) in the regulation
      of fetal metabolism, the kinetics of leucine, phenylalanine, and glucose were
      assessed in the chronically catheterized ovine fetus (0.85 gestation) before and
      during infusion of recombinant human IGF-I (rhIGF-I). Substrate kinetics were
      determined by tracer dilution. rhIGF-I was infused at 6.7 nmol.kg fetus-1.h-1.
      Fetal insulin and growth hormone concentrations were significantly decreased by
      50% during rhIGF-I infusion. Net umbilical glucose uptake was unchanged, and
      glucose rate of appearance increased in the fed state only. There were no changes
      in the net umbilical uptakes of leucine or phenylalanine, but the rates of
      appearance of both declined during rhIGF-I infusion, indicative of decreased
      fetal protein breakdown (Ra,Leu 45.4 +/- 1.40 to 40 +/- 1.4 mumol/min in the fed
      state, 43 +/- 1.5 to 37 +/- 1.5 mumol/min in the fasted state; Ra,Phe 10.7 +/-
      0.3 to 10.4 +/- 0.3 mumol/min in the fed state and from 10.7 +/- 0.3 to 9.8 +/-
      0.3 mumol/min in the fasted state). Leucine oxidation was also decreased (8.90 +/
      0.76 to 6.52 +/- 0.81 mumol/min, P = 0.025), more so in the fasted than the fed
      state. These results indicate a significant antiproteolytic endocrine effect for
      IGF-I in the late-gestation mammalian fetus.

PMID- 8760096
TI  - Fetal substrate uptake during increased ovine fetal cortisol concentration.
AB  - Corticosteroid administration adversely affects fetal growth and consequently,
      unless metabolic rate increases (thereby increasing the need for fetal metabolic
      substrates), reduces fetal need for exogenous substrates. To find whether the
      uptake of all or only certain metabolic substrates was affected by fetal
      hypercortisolemia, we measured exogenous uptake of glucose, lactate, and alpha
      amino nitrogen during fetal hypercortisolemia in seven late-gestation sheep
      fetuses. Hydrocortisone infusion increased fetal cortisol concentrations from
      normal to values usually associated with late gestation (4.3 +/- 0.9 vs. 72.5 +/-
      5.0 ng/ml; P < 0.001). In association with increased fetal cortisol
      concentration, both fetal metabolic rate and the uptakes of glucose and lactate
      remained constant. However, the uptake of alpha-amino nitrogen-containing
      substances fell (39.6 +/- 3.1 vs. 28.5 +/- 3.4 mumol.kg-1.min-1; P < 0.002) as
      did the proportion of metabolic rate (0.45 +/- 0.04 vs. 0.32 +/- 0.04; P < 0.002)
      that could be supported by metabolism of these substances. The proportion of
      fetal metabolic rate that could be supported by complete metabolism of all
      substrates taken up across the placenta decreased (1.09 +/- 0.07 vs. 0.95 +/-
      0.06; P < 0.02). In conclusion, hypercortisolemia alters the composition of
      oxidative substrates taken up by the sheep fetus and decreases total fetal
      substrate uptake. These changes occur within hours of exposure to increased
      cortisol concentration.

PMID- 8760097
TI  - Control of cell proliferation in the rat adrenal gland in vivo by the renin
      angiotensin system.
AB  - Adrenal cytogenesis was investigated in response to 1) subcutaneous infusions of
      angiotensin (ANG) II (200 ng.kg-1.min-1); 2) high and low sodium intake; and 3)
      captopril treatment (10 mg.kg-1.day-1). Cell proliferation was assessed as uptake
      of 5-bromo-2'-deoxyuridine (BrdUrd) into nuclei. BrdUrd, infused continuously
      throughout 2 wk of treatment, was detected immunocytochemically. ANG II and
      sodium restriction caused hypertrophy of the zona glomerulosa with two- to
      threefold increases in BrdUrd indexes. After captopril, the glomerulosa appeared
      atrophied with pyknotic nuclei, but the BrdUrd index was unchanged. Zonae
      intermedia and fasciculata were unaffected by any treatment. Zona reticularis
      epithelial cells proliferated in response to ANG II and sodium restriction but
      were unaffected by captopril. In the medulla, captopril increased BrdUrd uptake,
      whereas ANG II, but not low sodium, caused a decrease. In conclusion, 1)
      proliferation of the glomerulosa and reticularis cells is specifically controlled
      by ANG II, 2) captopril may cause glomerulosa cells to die, and 3) blood pressure
      may control proliferation of the medulla.

PMID- 8760098
TI  - Lack of effect of an acute ileal perfusion of short-chain fatty acids on glucose
      metabolism in healthy men.
AB  - Dietary fiber intake is associated with several beneficial effects on
      carbohydrate metabolism. Some authors have speculated that this improvement may
      be due to short-chain fatty acids (SCFA) produced by the colonic fermentation of
      dietary fibers. To test this hypothesis, six healthy men aged 26 +/- 2 (SE) yr
      with a body mass index of 20.9 +/- 0.7 received on three occasions an 18-h ileal
      perfusion infused at a flow rate of 3.3 ml/min, containing either 90 mmol/l of
      SCFA (60% acetate, 25% propionate, and 15% butyrate) (A), SCFA during the first
      12 h and then a saline solution (A/S), or a saline solution (S). Basal hepatic
      glucose production (BHGP), insulin sensitivity (3-step euglycemic-hyperinsulinic
      clamp), and erythrocyte insulin binding (EIB) were studied 12 h after the
      beginning of the ileal perfusion. There was no change in BHGP or insulin
      sensitivity. However, maximal EIB was significantly different: 7.1 +/- 0.1 (A),
      6.8 +/- 0.1 (A/S), vs. 6.5 +/- 0.1% (S) (P = 0.03). We conclude that acute
      administration of SCFA does not significantly alter glucose metabolism in healthy
      subjects.

PMID- 8760099
TI  - Fluid flow stimulates rapid and continuous release of nitric oxide in
      osteoblasts.
AB  - Interstitial fluid flow may mediate skeletal remodeling in response to mechanical
      loading. Because nitric oxide (NO) has been shown to be an osteoblast mitogen and
      inhibitor of osteoclastic resorption, we investigated and characterized the role
      of fluid shear on the release of NO in osteoblasts. Rat calvarial cells in a
      stationary culture produced undetectable levels of NO. Fluid shear stress (6
      dyn/cm2) rapidly increased NO release rate to 9.8 nmol.h-1.mg protein-1 and
      sustained this production for 12 h of exposure to flow. Cytokine treatment also
      induced NO synthesis after a 12-h lag phase of zero production, followed by a
      production rate of 0.6 nmol.h-1.mg protein-1. Flow-induced NO production was
      blocked by the NO synthase (NOS) inhibitor NG-amino-L-arginine, but not by
      dexamethasone, which suggests that the flow stimulated a constitutive NOS
      isoform. This is the first time that a functional constitutively present NOS
      isoform has been identified in osteoblasts. Moreover, fluid flow represents the
      most potent stimulus of NO release in osteoblasts reported to date. Fluid flow
      induced NO production may therefore play a primary role in bone maintenance and
      remodeling.

PMID- 8760100
TI  - Physiological mechanisms of cholecystokinin action on pancreatic secretion.
AB  - Recent experimental studies in animals and humans provide strong evidence that
      cholecystokinin (CCK) acts via cholinergic pathways to mediate pancreatic enzyme
      secretion. These studies indicate that the sites of CCK's action to stimulate
      pancreatic secretion are dose dependent. Doses of CCK that produce physiological
      plasma CCK levels act via stimulation of the vagal afferent pathway originating
      from the gastroduodenal mucosa, whereas doses that produce supraphysiological CCK
      levels act to stimulate intrapancreatic neurons and pancreatic acini. These CCK
      sensitive fibers are also responsive to a wide range of chemical and osmotic
      stimuli. In this manner, gastrointestinal afferents responding to hormones such
      as CCK and the ever-changing chemical and physical luminal environment provide
      sensory information to the central nervous system, which in turn stimulates
      pancreatic secretion via a vagal cholinergic pathway.

PMID- 8760101
TI  - Structural requirements of CCK analogues to differentiate second messengers and
      pancreatic secretion.
AB  - We previously demonstrated that, in rat pancreatic acinar cells, the high
      affinity cholecystokinin (CCK) receptor agonist JMV-180 utilizes the
      phospholipase A2 (PLA2) cascade to mediate Ca2+ oscillations and amylase
      secretion. In contrast, the low-affinity CCK receptor utilizes the phospholipase
      C beta 1 (PLC beta 1) pathway. We have investigated structural requirements of
      CCK analogues to activate different intracellular pathways. CCK analogues such as
      CCK-8 [Met28,31; half-maximal effective concentration (EC50) = 0.4 pM], CCK-7
      (Met28,31; EC50 = 0.7 pM), and NONA (Thr28/Nle31; EC50 = 5 pM) caused a biphasic
      amylase secretion. Reduction of secretion occurred with high doses of these
      peptides (> 100 pM). In contrast, CCK-5 (Met31; EC50 = 20,000pM), JMV-180
      (Nle28,31; 1,500 pM), and OPE (Nle28,31; 200 pM) caused a monophasic secretion.
      CCK-8, but not JMV-180, increased protein kinase C (PKC) activities. The PKC
      activator phorbol ester inhibited an increase in myo-inositol 1,4,5-trisphosphate
      levels induced by CCK-8 and abolished monophasic amylase secretion induced by
      OPE. CCK-8, CCK-7, and NONA caused Ca2+ oscillations (< 100 pM) or large Ca2+
      transients (> 100 pM). In contrast, JMV-180 and OPE evoked Ca2+ oscillations,
      even in high doses. Ca(2+)-signaling modes induced by CCK-5 were intermediate
      types between CCK-8 and JMV-180. CCK-8- and CCK-7-stimulated Ca2+ spikes were
      inhibited by the PLC inhibitor U-73122, but not by the PLA2 inhibitor ONO-RS-082.
      The action of CCK-5 was only partially sensitive to the PLC inhibitor. In
      contrast, JMV-180- and OPE-stimulated Ca2+ oscillations were inhibited by the
      PLA2, but not by the PLC, inhibitor. NONA was sensitive to PLC and PLA2
      inhibitors. Although JMV-180 differs from CCK-8 by having an Asp-2
      phenylethylester, rather than an Asp-phenylalanine amide, it is unlikely that
      these differences in the carboxyl terminus are important in determining which
      second-messenger systems will be activated. This is because CCK-5 (Phe33-CONH2)
      causes monophasic amylase secretion and Ca2+ oscillation in a manner similar to
      those induced by JMV-180 (2-phenylethylester). Meanwhile NONA (Phe33-CONH2)
      appeared to activate PLC and PLA2 pathways. The actions of all CCK analogues were
      abolished by L-364,718, indicating mediation by CCK-A receptors. Therefore,
      depending on the agonists used, CCK-A receptor activation in pancreatic acini may
      result in differential involvement of second-messenger systems, Ca2+ signal
      transduction, and amylase secretion. On the basis of the amino acid sequence of
      the carboxy terminus of CCK analogues, it appears that key amino acids for this
      differentiation are Met28 (or Thr28) for PLC pathways and Nle28 for PLA2
      pathways.

PMID- 8760102
TI  - Edema and intrapancreatic trypsinogen activation precede glutathione depletion
      during caerulein pancreatitis.
AB  - Acute pancreatitis is characterized by hyperamylasemia, pancreatic edema, and the
      presence of activated digestive enzymes within the pancreas. The secretagogue
      induced model of acute pancreatitis is also characterized by pancreatic acinar
      cell vacuolation, subcellular redistribution of lysosomal hydrolases, and a fall
      in pancreatic glutathione levels. We have performed time-dependence studies to
      determine the sequence with which these phenomena appear and to establish their
      cause-and-effect relationship. Evidence of lysosomal enzyme redistribution and
      trypsinogen activation within the pancreas could be detected within 10-15 min of
      the onset of supramaximal secretagogue stimulation, while hyperamylasemia (30
      min), pancreatic edema (60 min), and acinar cell vacuolation (60 min) occurred at
      later times. Pancreatic glutathione levels were either unchanged (15 and 30 min)
      or elevated (60 min) during the early times of supramaximal stimulation and were
      only noted to be decreased at a later time. These results support the conclusion
      that intrapancreatic digestive enzyme activation, possibly occurring by a
      mechanism involving lysosomal hydrolase redistribution, is an early and likely a
      critical event in the evolution of secretagogue-induced pancreatitis but that
      glutathione depletion is neither early nor critical to the evolution of this
      model of pancreatitis.

PMID- 8760103
TI  - Nitric oxide attenuates endothelin-1-induced vasoconstriction in canine stomach.
AB  - We previously observed that endothelin-1 (ET-1)-induced gastric vasoconstriction
      is enhanced after ischemia-reperfusion. The purpose of our present study was to
      examine the role of nitric oxide in regulating ET-1-induced vasoconstriction
      under normal conditions and after ischemia-reperfusion. Using a mechanically
      perfused stomach segment from chloralose-anesthetized dogs, we examined 1)
      responses to NG-nitro-L-arginine methyl ester (L-NAME) alone and in combination
      with L-arginine, 2) whether L-NAME affects ET-1-induced vasoconstriction under
      normal conditions and after ischemia-reperfusion, and 3) if spermine NONOate {1,3
      propanediamine-N-[4-1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazi no] butyl; a
      nitric oxide donor} attenuates the augmented response to ET-1 after ischemia
      reperfusion. Our results show that 1) L-NAME significantly increased baseline
      vascular resistance and this response was reduced by L-arginine, 2) ET-1-induced
      vasoconstriction was enhanced by L-NAME, and 3) administration of spermine
      NONOate during reperfusion largely attenuated the vasoconstrictor response to ET
      1 after ischemia-reperfusion. Our findings are consistent with the hypothesis
      that nitric oxide modulates responses to ET-1 under normal conditions, and loss
      of this vasodilator after ischemia-reperfusion results in an augmented response
      to ET-1.

PMID- 8760104
TI  - Peptide YY receptor in submucosal and myenteric plexus synaptosomes of canine
      small intestine.
AB  - PYY receptors were characterized and their loci determined in canine small
      intestine. The density of 125I-labeled peptide tyrosine tyrosine (PYY) binding
      was highest in myenteric (MY) and submucosal (SUB) plexus fractions enriched in
      synaptosomes. Two binding sites [high affinity (H) and low affinity (L)] were
      found in the submucosal synaptosome-enriched membrane: dissociation constant
      (Kd)H = 7.6 pM, maximal binding capacity (Bmax)H = 28 fmol/mg; KdL = 0.18 nM,
      BmaxL = 120 fmol/mg protein. The binding of 125I-PYY reached a maximum within 30
      min; dissociation was incomplete in the presence of unlabeled PYY. The rate of
      dissociation was enhanced after exposure of synaptosomes to guanosine 5'-O-(3
      thiotriphosphate). Binding of 125I-PYY was completely inhibited by neuropeptide Y
      (NPY)-(13-36) (in SUB and MY) and by [Leu31,Pro34]NPY (in MY) but only partially
      by [Leu31,Pro34]NPY in SUB, suggesting the presence of Y2 receptor in SUB and the
      presence of Y1 and Y2 receptors in MY. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analysis of the PYY receptor complex revealed a radioactive band
      at 70 kDa. The PYY receptors in the canine small intestinal myenteric and
      submucosal plexus correspond in location to that of PYY in synaptosomes and are
      coupled with G proteins. Different subtypes are present in different loci.

PMID- 8760106
TI  - Neural integration of jejunal motility and ion transport in nematode-infected
      ferrets.
AB  - Jejunal motility measured manometrically and coupled fluctuations in electrogenic
      ion transport measured as transmural potential differences (PD) were
      simultaneously studied in ferrets infected with enteric stages of the parasitic
      nematode, Trichinella spiralis. Vagotomy in uninfected ferrets abolished jejunal
      motility clusters and associated PD oscillations. Conversely, in infected ferrets
      on days 8-12 postinfection (PI), vagotomy did not abolish jejunal motility and
      PD. Calculated motility indexes (MI) indicated that postvagotomy MI decreased to
      12% of prevagotomy MI in uninfected ferrets, whereas, in T.spiralis-infected
      ferrets, postvagotomy MI declined only to 48% of prevagotomy MI. Atropine
      abolished all vagotomy-resistant residual jejunal motility clusters and PD
      oscillations in T. spiralis-infected ferrets. Decreased intestinal content of
      substance P (27% of control) and vasoactive intestinal peptide (41% of control)
      and increased myeloperoxidase activity (262% of control) were detected in T.
      spiralis-infected ferrets. Our results suggest that integrated neural control of
      muscular and epithelial effectors in the small bowel is altered by nematode
      induced inflammation.

PMID- 8760105
TI  - Significance of peptic digestion in rat pancreatic secretory response to dietary
      protein.
AB  - The importance of peptic digestion of dietary protein in pancreatic enzyme
      secretion and cholecystokinin (CCK) release was investigated in conscious rats.
      Native casein and native bovine serum albumin (BSA) were infused intragastrically
      and intra-intestinally, and the effect of peptic predigestion on the pancreatic
      secretory and plasma CCK responses to BSA were determined (all infused at 450
      mg/h). When dietary proteins were infused intraduodenally, native casein was a
      much stronger stimulant of CCK release (5.8 +/- 0.6 vs. 1.6 +/- 0.2 pM) and
      pancreatic protein secretion [5,592 +/- 736 vs. 750 +/- 461 (0-180)mg.kg-1.min]
      than native BSA. Infusion by the intragastric route markedly increased pancreatic
      protein secretion for BSA but not for casein. HCl-pepsin treatment of BSA
      significantly increased its ability to increase pancreatic secretion and plasma
      CCK. Pancreatic protease binding to native BSA was inferior compared with casein.
      Peptic digestion of BSA increased its protease binding activity more than
      threefold. The results indicate that peptic digestion of dietary proteins
      enhances the proteins' ability to elicit the pancreatic feedback stimulatory
      response.

PMID- 8760107
TI  - Membrane cholesterol alters gallbladder muscle contractility in prairie dogs.
AB  - The cause and effect relationship between membrane cholesterol and gallbladder
      muscle contractility was examined by altering membrane cholesterol to
      phospholipid mole ratio using cholesterol-rich or cholesterol-free liposomes.
      Gallbladder single muscle cells, from prairie dogs that were fed either a regular
      or high-cholesterol (1.2%) diet, were isolated enzymatically with collagenase.
      Plasma membranes of gallbladder muscle were purified in sucrose gradient.
      Cholesterol was measured using the cholesterol oxidase method. Phospholipids were
      measured with the method of G.R. Bartlett (J. Biol. Chem. 234: 466-468, 1959).
      The results of this experiment are 1) after high-cholesterol feeding, cholesterol
      contents and cholesterol/ phospholipid mole ratio in plasma membranes of
      gallbladder muscle increased 90%, and muscle cell contraction in response to
      cholecystokinin octapeptide decreased 58%; 2) similar changes were observed when
      normal gallbladder muscle cells were incubated with cholesterol-rich liposomes
      for 2 h; and 3) the changes induced either in vivo or in vitro were reversed when
      muscle cells were subsequently incubated with cholesterol-free liposomes for 2-6
      h. We conclude that gallbladder muscle may incorporate excess cholesterol into
      its plasma membrane when exposed to a cholesterol-rich environment, that excess
      membrane cholesterol impairs muscle contractility, and that these changes appear
      to be reversible.

PMID- 8760108
TI  - Fat absorption is not complete by midgut but is dependent on load of fat.
AB  - Since the intubation study of B. Borgstrom, A. Dahlqvist, and G. Lundh (J. Clin.
      Invest. 36: 1521-1536, 1957) in humans, the completion of fat absorption within
      the proximal small intestine has been widely accepted. Based on this report, it
      has been assumed that the distal small intestine is exposed to fat only in the
      setting of pathology. This concept may be flawed, since completeness of fat
      absorption was calculated from the recovery of a water-soluble marker but the
      aqueous phase is now known to move independently from fat. To reexamine the
      question of whether fat absorption is complete by midgut, we measured the
      recovery of a fat-specific marker, 99mTc-thiocyanate, in a canine model equipped
      with duodenal and midgut fistulas. The fistulous output allowed for the
      measurement of the amount of fat entering the small intestine and the amount of
      fat entering the distal one-half of the small intestine. Emulsion meals
      containing 15 or 60 g of corn oil were tested. The importance of fat exposure of
      the distal one-half of the small intestine was further confirmed by comparing the
      fistulous fat recovery under two different patterns of exposure [allowing (ALL)
      or denying (150 cm) access to the distal small intestine]. We found that fat
      recovery depended on 1) the dose of fat (15 vs. 60 g; P < 0.0005), 2) the pattern
      of exposure (150 cm vs. ALL; P < 0.01), and 3) the fistulous position (duodenal
      vs. midgut; P < 0.005). Specifically, under a 150-cm exposure pattern, whereas
      8.8 +/- 1.8 g (means +/- SE) of fat emptied into the duodenum after the 15-g fat
      meal, 32.6 +/- 3.2 g emptied after the 60-g fat meal. Correspondingly, although
      3.5 +/- 1.5 g of fat were recoverable from the midgut fistulous output after the
      15-g meal, a much larger amount, 17.1 +/- 5.6 g of fat, was recoverable and
      therefore not absorbed by the proximal one-half of the small intestine after the
      60-g meal. The amount of fat recovery at each fistula was reduced when chyme was
      allowed access to the whole gut (by triggering fat-induced ileal brake). We
      conclude that the intestinal length required for fat absorption depends on the
      load of fat in the meal so that, even after usual meals, absorption of fat is not
      complete by midgut.

PMID- 8760109
TI  - Positional specificity of defensin gene expression reveals Paneth cell
      heterogeneity in mouse small intestine.
AB  - Cryptdins are antimicrobial peptides of the defensin family that are expressed
      specifically by Paneth cells in small intestinal crypts (M.E. Selsted, S.I.
      Miller, A.H. Henschen, and A.J. Ouellette. J. Cell Biol. 118: 929-936, 1992), and
      at least 17 cryptdin isoforms have been reported in mouse small intestine (A.J.
      Ouellette, M.M. Hsieh, M.T. Nosek, D.F. Cano-Gauci, K.M. Huttner, R.N. Buick, and
      M.E. Selsted. Infect. Immun. 62: 5040-5047, 1994). Analysis of cryptdin gene
      expression in adult mouse small bowel revealed that the cryptdin-4 isoform is
      differentially expressed along the proximal-to-distal intestinal axis. By peptide
      specific reverse transcriptase-polymerase chain reaction-based assays, cryptdin-4
      mRNA was found to be absent from the proximal small bowel, increasing to maximal
      levels in the ileum. In contrast, intestinal content of cryptdin-1 and -5 mRNAs
      was equivalent in duodenum, jejunum, and ileum, and Northern blot hybridization
      experiments were consistent with both sets of data. Similarly, individual crypts
      isolated from duodenum contain cryptdin-1 mRNA but not cryptdin-4 mRNA. Taken
      together, the results show that Paneth cells are heterogeneous, depending on
      their position along the longitudinal axis of the small bowel. The positional
      specificity of defensin gene expression suggests that cryptdins may be useful
      markers for investigating the establishment and maintenance of this epithelial
      lineage in the mouse small intestine.

PMID- 8760110
TI  - Role of transforming growth factor-beta in the restitution of injured guinea pig
      gastric mucosa in vitro.
AB  - The role of transforming growth factor-beta (TGF-beta) in restitution was
      examined in intact sheets of injured guinea pig gastric mucosa in which the
      epithelial cell-collagen interaction can be quantitatively evaluated. The luminal
      surface of intact sheets of in vitro guinea pig gastric mucosa was injured by
      exposure to 1.25 mol/l NaCl for 10 min. Restitution was evaluated by measurement
      of transmucosal electrical resistance and [3H]mannitol flux before and after
      injury. Recovery of electrical resistance and [3H]mannitol flux was retarded by
      inhibition of endogenous TGF-beta with either aprotinin or anti-TGF-beta
      antibody; effects were restored by human recombinant TGF-beta1. During inhibition
      of endogenous TGF-beta, type IV collagen accelerated the recovery. Inhibition of
      reconstruction of the basement membrane by simultaneous addition of cis-4-OH-L
      proline and anti-type IV collagen completely abolished the enhancement of the
      recovery by TGF-beta 1. These results suggest that endogenous TGF-beta is
      required for restitution to occur in guinea pig gastric mucosa and that type IV
      collagen plays an important role in TGF-beta-abetted restitution.

PMID- 8760111
TI  - Characterization of cytosolic Ca2+ signaling in rat bile duct epithelia.
AB  - Bile duct epithelia play an important role in the formation and conditioning of
      bile. However, hormonal responses in this epithelial tissue are incompletely
      understood. Secretin increases ductular secretion through the intracellular
      messenger adenosine 3',5'-cyclic monophosphate (cAMP), but whether hormones
      increase cytosolic Ca2+ (Ca2+(i)) in these cells and whether Ca2+(i) regulates
      duct secretion is unknown. To address these questions, we examined Ca2+(i)
      signaling in isolated rat bile duct units using ratio microspectrofluorometry and
      confocal microscopy. We also used videomicroscopy to examine secretion and cell
      volume in isolated bile duct cells and duct units. Acetylcholine (ACh) and ATP
      both increased Ca2+(i) in bile duct units and elicited patterns of Ca2+(i)
      increases and oscillations that were distinct and dose dependent. In contrast,
      Ca2+(i) was not increased by the hepatocyte Ca2+(i) agonists vasopressin,
      angiotensin, and phenylephrine or by the exocrine pancreas agonists
      cholecystokinin (CCK) and bombesin. In addition, secretin did not increase
      Ca2+(i) in the isolated bile duct units, whereas ACh did not increase Ca2+(i) in
      isolated hepatocytes. Mobilization of internal, thapsigargin-sensitive Ca2+
      stores contributed more than influx of extracellular Ca2+ to the Ca2+(i)
      increases induced in the duct units, and ATP-induced increases in Ca2+(i) could
      be blocked by microinjection of heparin but not de-N-sulfated heparin. ACh
      transiently decreased bile flow in the isolated perfused rat liver, although
      neither ACh nor ATP altered secretion in isolated ducts or changed the volume of
      single isolated bile duct cells. These findings demonstrate that bile duct
      epithelial cells possess both muscarinic and purinergic receptors that activate
      Ca2+(i) signaling pathways similar to those seen in other types of epithelia, but
      that the two types of receptors elicit distinct patterns of Ca2+(i) signals.
      Increases in Ca2+(i) have minimal direct effects on bile duct secretion, although
      it remains to be determined whether such signals selectively modulate other
      aspects of bile duct epithelial cell function.

PMID- 8760112
TI  - A diet containing glycine improves survival in endotoxin shock in the rat.
AB  - In this study, we investigated the effects of a glycine-containing diet (5%) on
      mortality and liver injury due to intravenous injection of endotoxin [Escherichia
      coli lipopolysaccharide (LPS)] in Sprague-Dawley rats in vivo. Fifty percent of
      the rats fed control diet died within 24 h after an intravenous injection of LPS
      (10 mg/kg), whereas feeding the rats glycine totally prevented mortality and
      markedly reduced an LPS-induced elevation of serum transaminase levels, hepatic
      necrosis, and lung injury. The elevation in serum tumor necrosis factor-alpha
      (TNF-alpha) due to LPS was also blunted and delayed significantly by glycine
      feeding. In a two-hit model (hepatic ischemia-reperfusion and injection of
      sublethal LPS), all rats fed control diet died, whereas 83% of glycine-fed
      animals survived with a significant reduction in transaminases and improved liver
      and lung histology. LPS elevated intracellular Ca2+ concentration ([Ca2+]i) in
      cultured Kupffer cells, an effect blocked almost completely by glycine. Glycine
      most likely reduces injury and mortality by preventing the LPS-induced elevation
      of [Ca2+]i in Kupffer cells, thereby minimizing toxic eicosanoid and cytokine
      production.

PMID- 8760113
TI  - Insulin potentiates mitogenic effect of epidermal growth factor on cultured
      guinea pig gastric mucous cells.
AB  - Epidermal growth factor (EGF) stimulated proliferation of gastric mucous
      epithelial cells from guinea pigs in serum-free culture conditions. Western blot
      analysis with antiphosphotyrosine antibody showed that EGF initiated tyrosine
      phosphorylation of a 170-kDa protein, and this protein was identical to the EGF
      receptor. Insulin was not mitogenic, but it potentiated the mitogenic effect of
      EGF. Tyrosine phosphorylation of additional proteins was not induced by the
      combined actions of insulin and EGF. Stimulation by EGF and/or insulin did not
      cause a calcium response. However, when insulin was added to cells pretreated
      with EGF for > 6 h, it elicited a rapid intracellular calcium concentration rise
      that was reproducible in both cell suspension and single cell analyses. This
      calcium response coincided with the translocation of protein kinase C (PKC) from
      the cytosolic to the particulate fraction. Phorbol 12-myristate 13-acetate also
      caused the translocation and stimulated proliferation of the cells. These results
      suggest that the calcium-dependent activation of PKC may participate in the
      potentiation of the mitogenic effect of EGF by insulin.

PMID- 8760114
TI  - Inhibition of binding to fatty acid binding protein reduces the intracellular
      transport of fatty acids.
AB  - Male livers, containing lesser amounts of fatty acid binding protein (FABP),
      utilize fatty acids more slowly than female livers. Conventional wisdom dictates
      that FABP stimulates fatty acid use by increasing cytoplasmic transport rates.
      Previously, we showed that the cytoplasmic diffusion of a fatty acid analogue [12
      N-methyl-7-nitrobenzo-2-oxa-1,3-diazol-amino stearate (NBD-stearate)] is faster
      in female hepatocytes, paralleling the larger amounts of FABP. Sex differences in
      other cytoplasmic factors could also lead to faster diffusion, independent of
      FABP levels. The aim of this study was to determine the effect of inhibition of
      fatty acid binding to FABP on the directly measured intracellular transport rate
      of NBD-stearate. The binding of NBD-stearate to FABP was reduced by incubating
      hepatocytes isolated from male and female rats with alpha-bromo-palmitate (0
      1,500 microM), a modified long-chain fatty acid that binds to FABP. The
      inhibition by alpha-bromo-palmitate on NBD-stearate binding to FABP was measured
      with the use of centrifugation to separate cytosol from cytoplasmic membranes.
      Laser photobleaching (fluorescence recovery after photobleaching) was used to
      measure the cytoplasmic diffusion of NBD-stearate in hepatocytes. Alpha-Bromo
      palmitate incubation reduced NBD-stearate binding to FABP in a dose-dependent
      manner. The measured diffusion rate was also reduced in proportion to the degree
      of binding inhibition. We conclude that cytoplasmic transport of NBD-stearate is
      modulated by binding to soluble proteins like FABP. FABP enhances diffusive
      transport by reducing binding to immobile cytosolic membranes.

PMID- 8760116
TI  - Kinetics of cytokine expression during healing of acute colitis in mice.
AB  - The mechanisms of wound healing in the gut are poorly understood but are mediated
      by cytokines in other tissues. In this study we wanted to determine which
      cytokines were expressed after nonspecific colonic injury, the kinetics of that
      expression, and how cytokine expression correlated with tissue histology. At 0,
      4, 8, 12, 24, 48, and 72 h after intrarectal administration of 3% acetic acid to
      C3H/HeJ mice, their colons were removed for histology, organ culture, and RNA
      extraction. Cytokine mRNA expression for various cytokines was assessed by
      reverse transcriptase-polymerase chain reaction with primers specific for each
      cytokine. Cytokine production in organ cultures was measured with bioassays.
      Shortly after colonic injury and during colonic regeneration, proinflammatory
      cytokines such as interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor
      alpha (TNF-alpha), macrophage inflammatory protein (MIP), and transforming growth
      factor-beta (TGF-beta) were expressed. In contrast, expression of T cell-derived
      cytokines was not detected at any time point. Cytokines such as IL-1 beta, IL-6,
      IL-10, TNF-alpha, and MIP-1 are important mediators of tissue repair and
      restitution after nonspecific colonic injury and may subserve a similar role in
      human colitis.

PMID- 8760115
TI  - Expression of PRL-1 nuclear PTPase is associated with proliferation in liver but
      with differentiation in intestine.
AB  - Mechanisms controlling the tyrosine phosphorylation of cellular proteins are
      important in the regulation of cellular processes including growth and
      differentiation. It has become clear that a number of protein tyrosine
      phosphatases (PTPases) that dephosphorylate tyrosyl residues may play a role in
      the growth response, both in growth-promoting and growth-inhibiting capacities.
      We identified PRL-1, a unique nuclear PTPase that is an immediate-early gene in
      liver regeneration and is positively associated with growth, including fetal and
      neoplastic hepatic growth and anchorage-independent growth after overexpression
      in fibroblasts. In this study, we show that PRL-1 nuclear protein levels in
      regenerating liver parallel those of its mRNA, although the peak occurs later,
      just before the onset of DNA synthesis. We further show that PRL-1 is
      significantly expressed in intestinal epithelia and that, in contrast to the
      expression pattern of PRL-1 in liver, its expression is associated with cellular
      differentiation in intestine. Specifically, PRL-1 is expressed in villus but not
      crypt enterocytes and in confluent differentiated but not undifferentiated
      proliferating Caco-2 colon carcinoma cells. The expression of PRL-1 in intestine
      shows inverse correlation with proliferating cell nuclear antigen expression, a
      marker for S-phase cells. These results suggest that PRL-1 may play different
      roles in these two digestive tissues. Such a dichotomy of roles has previously
      been described for some protein tyrosine kinases and might be due to the
      availability of alternate substrates in different tissues.

PMID- 8760117
TI  - Effect of endotoxin on bile acid transport in rat liver: a potential model for
      sepsis-associated cholestasis.
AB  - Intrahepatic cholestasis in the setting of extrahepatic bacterial infection has
      been attributed to the effects of endotoxin and cytokines such as tumor necrosis
      factor-alpha (TNF-alpha) on bile acid transport. To define the mechanism of
      sepsis-associated cholestasis, taurocholate transport was examined in basolateral
      (bLPM) and canalicular (cLPM) rat liver plasma membrane vesicles derived from
      control and endotoxin [lipopolysaccharide (LPS)]-treated animals and in plasma
      membrane vesicles prepared after TNF-alpha treatment. Na(+)-dependent
      [3H]taurocholate uptake and both membrane-potential-dependent and ATP-dependent
      [3H]taurocholate transport were reduced in bLPM and cLPM vesicles, respectively,
      after LPS treatment. In membrane vesicles from TNF-alpha-treated animals, Na(+)
      dependent [3H]taurocholate uptake was also reduced. Northern blot hybridization,
      using cDNA probes for the putative sinusoidal bile acid transporter (Ntcp) and
      canalicular ecto-adenosinetriphosphatase, demonstrated decreased mRNA levels
      after LPS and TNF-alpha treatment. Immunoblot analysis of membrane extracts from
      LPS-treated animals revealed decreased levels of these putative bile acid
      transporters. Impaired bile acid transport at the sinusoidal and canalicular
      membrane domains by these and other mediators of the inflammatory response may
      account for sepsis-associated cholestasis.

PMID- 8760118
TI  - Carbachol, but not forskolin, increases mucosal-to-serosal transport of intact
      protein in rat ileum in vitro.
AB  - The effects of the secretagogues forskolin and carbachol on protein uptake in
      isolated ileum of rats were studied. The mucosal-to-serosal transport of
      horseradish peroxidase (HRP, mol mass 40 kDa) was measured in Ussing chambers,
      and afterwards tissues were processed for electron microscopy. In the absence of
      secretagogues, the flux of enzymatically active HRP was 5 pmol.cm-2.h-1 at a
      mucosal concentration of 10 microM. Electron micrographs showed vesicles filled
      with active HRP in enterocytes but no HRP activity in intercellular spaces.
      Forskolin decreased HRP activity in the cells. Carbachol increased the amount of
      HRP-filled vesicles in enterocytes and induced HRP filling in some intercellular
      spaces and tight junctions in the upper parts of the villi. The transepithelial
      flux of intact HRP increased more than 2.5-fold. This effect was suppressed by
      atropine. We conclude that cholinergic activation can increase the uptake of
      intact protein via endocytosis and the transepithelial passage by the induction
      of a diffusional paracellular pathway. We speculate that the increased transport
      of intact protein through the intestinal barrier may influence immunologic
      sensitization to food allergens.

PMID- 8760119
TI  - Pharmacokinetics and organ metabolism of carboxyamidated and glycine-extended
      gastrins in pigs.
AB  - The elimination of carboxyamidated gastrin-17 and its glycine-extended precursor
      was studied in anesthetized pigs during constant-rate infusion. Extraction of
      amidated gastrin-17 was recorded in the hindlimb (42%), kidney (40%), head (32%,
      P < 0.001), and the gut (13%, P < 0.01). Elimination was not recorded in the
      liver, lungs, or heart. Extraction of glycine-extended gastrin-17 was measured in
      the kidney (36%), hindlimb (31%, P < 0.001), head (26%), and the gut (16%, P <
      0.01), but not in the liver or the lungs. Glycine-extended gastrin-17 was not
      processed to amidated gastrin during infusion. The half-life, metabolic clearance
      rate, and apparent volume of distribution for amidated gastrin-17 were 3.5 +/-
      0.4 min, 15.5 +/- 1.1 ml.kg-1.min-1, and 76.5 +/- 9.9 ml/kg, respectively, and
      for glycine-extended gastrin-17 were 4.3 +/- 0.6 min, 17.4 +/- 0.9 ml.kg-1.min-1,
      and 104.7 +/- 11.9 ml/kg, respectively. We conclude that extraction of amidated
      and glycine-extended gastrin-17 varies in the vascular beds, with elimination
      mainly confined to nonorgan tissues and the kidneys.

PMID- 8760120
TI  - Expression of the ornithine decarboxylase gene in response to asparagine in
      intestinal epithelial cells.
AB  - Refeeding fasted rats significantly stimulates mucosal growth and ornithine
      decarboxylase (ODC), the rate-limiting enzyme in the biosynthesis of polyamines,
      but the exact mechanism responsible for induction of ODC at the molecular level
      is unknown. Of normal dietary constituents, the amino acid asparagine markedly
      increases ODC activity and mucosal growth when administered intragastrically. The
      current study examined the expression of the ODC gene in IEC-6 cells (a line of
      normal rat small intestinal crypt cells) after exposure to asparagine. Cells were
      grown in Dulbecco's minimal essential medium containing 5% dialyzed fetal bovine
      serum. They were deprived of serum for 24 h before experiments. Exposure to
      asparagine at the dose of 10 mM resulted in the rapid increase in ODC mRNA
      levels. The increased expression of the ODC gene began 1 h after and peaked
      between 3 and 5 h after treatment with asparagine. Maximum increases in ODC mRNA
      levels were approximately fivefold the normal value. Increased levels of ODC mRNA
      in cells exposed to asparagine were paralleled by increases in ODC protein and
      enzyme activity and cellular polyamine levels. The half-life of mRNA for ODC in
      unstimulated IEC-6 cells was approximately 30 min and increased to > 2 h in cells
      exposed to 10 mM asparagine. The half-life of ODC activity also was increased in
      asparagine-treated cells. When cellular protein synthesis was inhibited by
      cycloheximide, asparagine superinduced ODC mRNA levels. Furthermore, asparagine
      also significantly stimulated DNA synthesis in IEC-6 cells. These results
      indicate that 1) asparagine stimulates ODC in IEC-6 cells through multiple
      pathways and 2) increased ODC mRNA levels result partly from a delay in the rate
      of degradation. These findings suggest that luminal amino acids stimulate gut
      mucosal growth in association with their ability to regulate ODC gene expression.

PMID- 8760121
TI  - Physicochemical characteristics of emulsions during fat digestion in human
      stomach and duodenum.
AB  - Seven fasting subjects were fitted with nasogastric and nasoduodenal tubes and
      received intragastrically a coarsely emulsified test meal. Gastric and duodenal
      aspirates were collected after 1, 2, 3, and 4 h. In the duodenum, most lipids (>
      90%) were present as emulsified droplets 1-100 microns in size. Large droplets
      and unemulsified material present in the test meal (> 100 micron) disappeared,
      whereas smaller droplets (1-50 microns) were generated after 1 h of digestion.
      Thus the median lipid droplet diameter significantly decreased (19.6 vs. 56.5
      microns in the test meal) and the droplet surface area significantly increased
      (1.58 vs. 0.70 micron2/g fat). Intermediate droplet diameters were 34.3, 46.3,
      and 27.6 microns after 2, 3, and 4 h, respectively. In the stomach, a comparable
      emulsion particle size pattern was observed, with median droplet diameters of
      17.2, 37.9, 52.4, and 41.6 microns after 1, 2, 3, and 4 h, respectively. However,
      the extent of triglyceride hydrolysis was much lower in the stomach (6-16%) than
      in the duodenum (42-45%), where small droplets were enriched in lipolytic
      products, cholesterol, and phospholipids. The present findings show for the first
      time that most dietary lipids are present in the human duodenum as emulsified
      droplets 1-50 microns in size and that no further marked emulsification of
      dietary fat occurs in the duodenum compared with the stomach.

PMID- 8760122
TI  - Changes in electrical and mechanical activity during ontogeny of the canine
      proximal colon.
AB  - The ontogenetic development of the circular muscle layer of the canine proximal
      colon was studied in animals from midway through gestation to 30 days old. With
      age, there was an increase in resting membrane potential along the submucosal
      surface and a decrease along the myenteric surface of the circular layer.
      Coinciding with the changes in membrane potential, slow waves increased in
      amplitude along the submucosal border and decreased in amplitude along the
      myenteric border. Muscle strips from animals midway through gestation were
      mechanically quiescent; however, 1 wk before birth spontaneous activity was
      observed. Electrical field stimulation of enteric nerves increased spontaneous
      contractions; this increase in activity was reversed to inhibition by atropine.
      In the presence of atropine and N omega-nitro-L-arginine or N omega-nitro-L
      arginine methyl ester, a noncholinergic excitation was revealed at stimulation
      frequencies > 5 Hz. The results of these studies provide evidence that the canine
      proximal colon is spontaneously rhythmic and that a functional innervation to the
      circular muscle layer exists before birth. The gradient in resting membrane
      potential across the circular layer is absent at birth but develops within 2-3 wk
      after parturition.

PMID- 8760123
TI  - Adaptations of intestinal nutrient transport to chronic caloric restriction in
      mice.
AB  - Lifelong caloric restriction increases median and maximum life span and retards
      the aging process in many organ systems of rodents. Because the small intestine
      absorbs a reduced amount of nutrients each day, does lifelong caloric restriction
      induce adaptations in intestinal nutrient transport? We initially compared
      intestinal transport of sugars and amino acids between 24-mo-old mice allowed
      free access to food [ad libitum (AL)] and those provided a calorically restricted
      [40% less than ad libitum (CR)] diet since 3 mo of age. We found that CR mice had
      significantly greater transport rates for D-glucose, D-fructose, and several
      amino acids and had significantly lower villus heights. Total intestinal
      absorptive capacities for D-glucose, D-fructose, and L-proline were each 40-50%
      greater in CR mice; absorptive capacity normalized to metabolic mass (body weight
      0.75) was approximately 80% greater in CR mice. Comparison of uptakes in aged AL
      and CR mice with previously published results in young AL mice suggests that
      caloric restriction delays age-related decreases in nutrient transport. In
      contrast to published studies in hibernation and starvation, chronic caloric
      restriction enhances not only uptake per milligram but also uptake per
      centimeter. We then switched 24-mo-old AL mice to a calorie-restricted diet for 1
      mo and found that short-term caloric restriction has no effect on intestinal
      nutrient transport, intestinal mass, and total absorptive capacity. Thus chronic
      but not short-term caloric restriction increases intestinal nutrient transport
      rates in aged mice, and the main mechanism underlying these increases is enhanced
      transport rates per unit intestinal tissue weight.

PMID- 8760124
TI  - Dynamics of arterial and portal venous flow interactions in perfused rat liver:
      an intravital microscopic study.
AB  - Intravital epifluorescent microscopy was used to quantitate microvascular
      parameters in the single-pass, dually perfused rat liver preparation. Livers
      perfused via the hepatic artery (HA) and portal vein (PV) at physiological
      pressures and perfusion rates responded to vasoactive agents and exhibited the HA
      buffer response. The distribution of arterial blood was found to be highly
      heterogeneous, whereas PV flow was distributed uniformly. The intrasinusoidal
      velocity of fluorescein isothiocyanate (FITC)-labeled red blood cells (RBCs)
      arriving from the HA was higher than that for RBCs arriving from the PV,
      indicating a shorter transit time for the arterially delivered FITC-RBCs.
      Experiments on livers perfused simultaneously via the HA and retrogradely via the
      hepatic vein revealed the presence of arteriovenous shunts, with some of the
      arterially delivered FITC-RBCs reaching the terminal hepatic venules via direct
      channels without traversing the sinusoidal bed. In livers perfused portally only,
      changes in PV flow rate (from 8 to 20 ml/min) produced small changes in perfusion
      pressure but large changes in vascular diameters, while portal pressure and
      transit time of portal blood remained relatively constant. In experiments
      designed to identify the location of hepatic vascular resistance, it was observed
      that hepatic venular diameters measured in the preparation under identical
      pressure and flow conditions were greater during retrograde than during prograde
      perfusion, suggesting that the site of hepatic vascular resistance is
      presinusoidal or sinusoidal.

PMID- 8760125
TI  - Hexose transporter expression in rat small intestine: effect of diet on diurnal
      variations.
AB  - In rodents, a number of intestinal digestive and absorptive processes demonstrate
      a diurnal pattern of activity. To investigate if the jejunal hexose transporters
      are regulated in such a diurnal fashion, the levels for the glucose and fructose
      transporter mRNA and proteins were determined at 6-h intervals over a 24-h
      control fed period. SGLT-1, GLUT-2, and GLUT-5 mRNA levels increased between two-
      and eightfold before the onset of peak feeding. GLUT-5 protein levels also varied
      in a diurnal fashion but were out of phase with the observed changes in GLUT-5
      mRNA levels. In contrast, GLUT-2 protein levels remained relatively constant
      during the control fed 24-h period. The effect of dietary manipulations on the
      observed diurnal variation was also investigated. After only 3 h of feeding a 60%
      fructose-enriched diet, the levels of GLUT-5 mRNA and protein were significantly
      elevated. GLUT-5 mRNA and protein levels remained elevated relative to the level
      of control diet-fed animals over the ensuing 24 h and during the 7th day of
      fructose feeding. Exposure to elevated levels of fructose had no significant
      effect on the diurnal pattern of GLUT-2 and SGLT-1 mRNA. In contrast, GLUT-2
      protein was rapidly downregulated during the length of the fructose feeding
      study. In conclusion, the data demonstrate a normal daily variation in the level
      of hexose transporter expression that can be rapidly modulated by diet.

PMID- 8760126
TI  - Measurement of proximal and distal gastric motility with magnetic resonance
      imaging.
AB  - The precise motor mechanisms associated with gastric emptying of nutrient liquids
      are unclear, in part because of difficulties in measuring the motility from the
      proximal and distal stomach simultaneously. We have now examined proximal and
      distal gastric motility, using a novel magnetic resonance imaging (MRI)
      technique. In seven healthy volunteers (4 males, 3 females; 27-37 yr), gastric
      emptying and motility were determined on two occasions after ingestion of 500 ml
      10% and 25% dextrose labeled with 1 mM gadolinium tetraazacyclododecane
      tetraacetic acid, using a 1.5-tesla Philips Gyroscan ACS II scanner. Gastric
      emptying was determined every 15 min with a series of transaxial scans. After
      each series of transaxial scans, 120 coronal scans, 1.2 s apart, were performed
      through the antrum and proximal stomach. For each coronal slice the diameters of
      the proximal stomach and the antrum were measured to determine the number of
      contractions per minute and depth (%basal diameter). Gastric emptying (half
      emptying time) was faster after ingestion of 10% compared with 25% dextrose (49
      +/- 15 vs. 118 +/- 37 min; P < 0.01). After both meals, the diameter of the
      proximal stomach remained relatively constant, whereas there were marked
      fluctuations in the diameter of the antrum. Mean (+/- SD) frequency (2.8 +/- 0.6
      vs. 2.0 +/- 0.8/min; P < 0.001) and depth (40 +/- 17% vs. 34 +/- 16%; P < 0.04)
      of antral contractions were higher after 10% dextrose compared with 25% dextrose.
      Rapid MRI techniques allow simultaneous measurement of both gastric emptying and
      motor function of different gastric regions. The increase in the frequency and
      depth of distal gastric contractions during ingestion of 10% compared with 25%
      dextrose supports the concept that the antrum contributes to the regulation of
      gastric emptying of nutrient liquids.

PMID- 8760127
TI  - Biophysical and molecular properties of amiloride-inhibitable Na+ channels in
      alveolar epithelial cells.
AB  - The recent immunopurification and cloning of various lung Na+ channel proteins
      has provided the necessary tools to study Na+ transport at a fundamental level
      across a number of epithelial tissues. Various macroscopic measurements of Na+
      transport have shown that Na+ ions enter the cytoplasm of alveolar cells mainly
      through amiloride-inhibitable Na+ channels. Molecular biology studies have shown
      the existence of three Na+ channel subunit mRNAs (alpha-, beta-, and gamma-rENaC)
      in mature fetal (FDLE) and adult alveolar type II (ATII) cells. Patch-clamp
      studies have demonstrated the existence of various types of amiloride-inhibitable
      Na+ channels, located in the apical membranes of FDLE and ATII cells. beta
      Agonists and agents that enhance intracellular adenosine 3',5'-cyclic
      monophosphate levels increase the open probability of these channels, leading to
      increased Na+ transport across the alveolar epithelium in vivo.
      Immunopurification of a putative channel protein from adult ATII cells showed
      that it contains an amiloride-binding subunit with a molecular mass of 150 kDa.
      When this protein was reconstituted in planar lipid bilayers, it exhibited single
      channels with a conductance of 25 pS, which were moderately selective for Na+
      over K+. The open probability of these channels was increased by the addition of
      protein kinase A (PKA) and ATP, and was decreased to the same extent by addition
      of [N-ethyl-N-isopropyl]-2'-4'-amiloride (EIPA) and amiloride (1 microM each) in
      the apical side of the bilayer, in agreement with the results of patch-clamp
      studies in ATII cells. Exposure of rats to sublethal hyperoxia increased alpha
      rENaC mRNA and the functional expression of Na+ channels in alveolar epithelial
      cells and limited alveolar edema. These findings indicate that alveolar
      epithelial channels contain at least one family of amiloride-sensitive Na+
      channel proteins, which displays a number of unique properties, including
      sensitivity to EIPA.

PMID- 8760128
TI  - Nitric oxide alters metabolism in isolated alveolar type II cells.
AB  - Alveolar type II cells may be exposed to nitric oxide (.NO) from external
      sources, and these cells can also generate .NO. Therefore we studied the effects
      of altering .NO levels on various type II cell metabolic processes. Incubation of
      cells with the .NO generator, S-nitroso-N-acetylpenicillamine (SNAP; 1 mM), leads
      to reductions of 60-70% in the synthesis of disaturated phosphatidylcholines
      (DSPC) and cell ATP levels. Cellular oxygen consumption, an indirect measure of
      cell ATP synthesis, is also reduced by SNAP. There is no direct effect of SNAP on
      lung mitochondrial ATP synthesis, suggesting that .NO does not directly inhibit
      this process. On the other hand, incubation of cells with NG-nitro-L-arginine
      methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), the enzyme
      responsible for .NO synthesis, results in increases in DSPC synthesis, cell ATP
      content, and cellular oxygen consumption. The L-NAME effects are reversed by
      addition of L-arginine, the substrate for NOS. Production of .NO by type II cells
      is inhibited by L-NAME, a better inhibitor of constitutive NOS (cNOS) than
      inducible NOS (iNOS), and is reduced in the absence of external calcium.
      Aminoguanidine, a specific inhibitor of iNOS, has no effect on cell ATP content
      or on .NO production. These results indicate that alveolar type II cell lipid and
      energy metabolism can be affected by .NO and suggest that there may be cNOS
      activity in these cells.

PMID- 8760129
TI  - Regulation of ornithine decarboxylase by hypoxia in pulmonary artery smooth
      muscle cells.
AB  - The polyamines are a family of low-molecular-weight organic cations that play
      essential intracellular regulatory roles in cell growth and differentiation.
      Elevations in cellular polyamine contents necessary for most physiological and
      pathological events in the lung appear to be driven by increase de novo
      synthesis. In contrast, increases in lung cell polyamines required for hypoxic
      pulmonary vascular disease can be attributed to augmented transmembrane polyamine
      transport which may, in turn, be the result of hypoxia-related decreases in the
      activity of the initial and generally rate-limiting enzyme in de novo polyamine
      synthesis, ornithine decarboxylase (ODC). To begin to define the unusual
      mechanism whereby hypoxia governs polyamine regulatory pathways, the present
      study examined the impact of varying severity and durations of hypoxic exposure
      on ODC activity and mRNA content in cultured bovine main pulmonary artery smooth
      muscle cells (PASMC). The effect of hypoxia on the activity of another rate
      limiting enzyme in polyamine synthesis, S-adenosylmethionine decarboxylase
      (AdoMet-DC), also was examined. Hypoxia caused time-dependent decreases in ODC
      and AdoMet-DC activities that were related to the severity of hypoxic exposure.
      Similarly, ODC mRNA content also was depressed by hypoxic exposure. The
      relationship between the decline in ODC activity and mRNA content was roughly
      linear. To determine whether hypoxia impairs ODC mRNA stability, two different
      inhibitors of transcription and Northern analyses were used to follow the decay
      in ODC mRNA abundance in hypoxic and normoxic PASMC. Densitometric scanning of
      Northern analysis indicated that ODC mRNA stability did not differ between
      hypoxic and normoxic PASMC. These results suggest that the reduction in ODC
      activity provoked by hypoxia in cultured bovine PASMC can be ascribed in part to
      a diminished transcriptional rate rather than to alterations in mRNA stability.

PMID- 8760130
TI  - Alteration of lung atrial natriuretic peptide receptors in genetic
      cardiomyopathy.
AB  - These studies were designed to characterize the atrial natriuretic peptide (ANF)
      receptor subtypes [guanylyl cyclase natriuretic peptide receptors (NPR-A, NPR-B)
      and NPR-C] in lungs of normal hamsters and to evaluate alterations in receptor
      kinetics in genetic cardiomyopathy (CMO), a model of human congestive heart
      failure. Lung membranes were obtained from normal and CMO 200-to 230-day-old
      hamsters. Cross-linking and competitive binding receptor assays using 125I
      labeled human ANF showed that lung membranes exhibit NPR, mainly guanylyl cyclase
      NPR-A and clearance NPR-C receptors. Stimulation of guanylyl cyclase by ANF and C
      type natriuretic peptide (CNP) confirmed the presence of NPR-A and NPR-B. The
      maximum binding capacity of total ANF binding sites (442 +/- 68 vs. 271 +/- 57
      fmol/mg protein, P < 0.05) was reduced, but dissociation constant (0.26 +/- 0.04
      vs. 0.41 +/- 0.08 nM) was not altered in CMO animals. Similar reductions were
      observed in the binding sites for brain natriuretic peptide (BNP; 438 +/- 83 vs.
      236 +/- 53 fmol/mg protein) and CNP (321 +/- 80 vs. 165 +/- 56 fmol/mg protein, P
      < 0.05) which may reflect a decline in NPR-A and NPR-B and/or NPR-C. Acid wash
      improved binding of 125I-labeled rat ANF to lung membranes of both normal and CMO
      hamsters, but the tendency towards reduced binding in CMO hamsters did not reach
      statistical significance, implying that downregulation may not have been due only
      to prior occupancy of the receptors. Transcripts of NPR-A, NPR-B, and NPR-C
      receptors in hamster lungs were detected by quantitative polymerase chain
      reaction. Compared with normal controls, the CMO hamster lung NPR-A mRNA was
      reduced by 50%, but NPR-B mRNA and NPR-C mRNA were not altered. Moreover, CMO
      hamster lungs showed less activation of guanylyl cyclase by ANF. These studies
      demonstrate that lung NPR are downregulated in hamster CMO.

PMID- 8760131
TI  - Hepatocyte growth factor is a mitogen for alveolar type II cells in rat lavage
      fluid.
AB  - Proliferation of type II cells is required for maintenance of the alveolar
      epithelium and for restoration after lung injury. Although various known growth
      factors have been reported to stimulate type II cell proliferation in vitro,
      there is very little knowledge on which growth factors are present in the lung in
      vivo. We have previously reported that rat lavage fluid contains a mitogen(s) for
      type II cells, and this study was de signed to identify the growth factor(s) in
      this biological fluid for type II cells. The mitogenic activity was purified by
      sequential chromatography on blue Sepharose and heparin Sepharose. Hepatocyte
      growth factor (HGF) and acidic fibroblast growth factor by Western analysis. The
      amount of HGF recovered by lavage was approximately 6 ng/rat. By a use of
      neutralizing antibodies for different growth factors, HGF was found to be
      responsible for most of the stimulatory activity for rat type II cells in the
      partially purified lavage fluid. In addition to HGF, rat lavage fluid also
      contained potent mitogenic activity for fibroblasts. Finally, we have
      demonstrated that much of the mitogenic activity in salt extracts of human lung
      is HGF. We conclude that HGF is found in rat lavage fluid and is possibly an
      important mitogen for adult type II cells in vivo.

PMID- 8760132
TI  - Dynamics of TGF-beta 3 peptide activity during rat alveolar epithelial cell
      proliferative recovery from acute hyperoxia.
AB  - Hyperoxia causes a reproducible pattern of lung injury and recovery,
      characterized by proliferation of type II alveolar epithelial cells (AEC2) during
      the recovery phase. We measured TGF-beta peptide production by AEC2 and
      macrophages from lungs of adult male rats exposed to 100% oxygen for 48 h and
      then allowed to recover for up to 72 h in room air. TGF-beta peptide activity
      levels were measured using the PAI-1 promoter-luciferase mink lung epithelial
      cell assay and characterized with peptide specific inhibitory antibodies. Control
      AEC2 produced 997 +/- 54 pg active TGF-beta x 10(6) cells-1.24h-1 (mean +/- SD),
      of which > 70% was TGF-beta 3, while cultured macrophages produced 58 +/- 17 pg
      active TGF-beta x 10(6) macrophages-1.24 h-1, > 80% of which was TGF-beta 1.
      During hyperoxia and recovery, active TGF-beta 3 production by AEC2 decreased by
      75%, with a nadir at 24 h recovery (P < 0.005). In contrast, TGF-beta peptide
      activity increased from undetectable levels in lung lavage from control rats to a
      peak of 1,470 +/- 743 pg/rat after 48 h oxygen exposure and 24 h recovery, while
      lavaged macrophage TGF-beta production in culture also increased threefold to a
      peak of 150 +/- 5 pg. 10(6) cells-1. 24 h-1 after 48 h oxygen exposure (P <
      0.005). The nadir of active TGF-beta 3 production by AEC2 coincided with the peak
      of the AEC2 proliferative phase of repair as determined by BrdU incorporation and
      FACS analysis of freshly isolated AEC2. We conclude that active TGF-beta 3
      production by AEC2 is dynamically downregulated during the proliferative phase of
      recovery from acute hyperoxic injury in rat. We speculate that decreased
      autocrine negative regulation of AEC2 proliferation by TGF-beta 3 may facilitate
      AEC2 proliferation during recovery from acute hyperoxic injury.

PMID- 8760133
TI  - Fibronectin modulates expression of interleukin-1 beta and its receptor
      antagonist in human mononuclear cells.
AB  - Identification of factors that regulate production of proinflammatory cytokines
      may provide insight into mechanisms governing lung inflammation. One potential
      regulatory factor highly expressed in inflamed tissues is fibronectin (FN). To
      determine the potential effects of FN on interleukin (IL)-1 beta production, we
      exposed human peripheral blood mononuclear cells to soluble FN. This treatment
      resulted in the accumulation of IL-1 beta mRNA and enhancement of IL-1 beta
      protein synthesis and secretion. This effect was dose dependent and appeared to
      be mediated by the integrin alpha 5 beta 1. Treatment with FN also increased
      production of IL-1 receptor antagonist (IL-1ra), a naturally occurring inhibitor
      of IL-1 function. However, the stimulatory effect of FN on IL-1ra production was
      abolished by costimulation with type I collagen. We conclude that the increased
      deposition of FN in injured tissues may enhance the expression of IL-1 beta mRNA
      and augment the production and release of IL-1 beta protein by mononuclear cells.
      Differential expression of IL-1 beta and IL-1ra resulting in a high IL-1 beta-to
      IL-1ra ratio in response to mixed matrices containing FN and type I collagen may
      be an important regulatory point in inflammation.

PMID- 8760134
TI  - Inhibition of Na-K-ATPase activity after prolonged hypoxia in an alveolar
      epithelial cell line.
AB  - Exposure to alveolar hypoxia may induce acute pulmonary edema. Because the
      vectorial sodium transport by alveolar epithelium represents an important
      mechanism for alveolar edema clearance, we examined whether hypoxia affects Na-K
      ATPase activity in cultured SV40-transformed rat alveolar type II cells (SV40
      ATII cells). Hypoxic exposures (O or 5% O2 for at least 12 h) induced a time- and
      O2 concentration-dependent decrease in ouabain-sensitive rubidium (osRb) influx.
      Neither the sensitivity of Rb influx to ouabain nor the maximum velocity of the
      enzyme measured on crude cell homogenates was affected by hypoxia. The osRb
      influx decrease was independent of hypoxia-induced ATP depletion. Na-K-ATPase
      inhibition was most likely related to impaired calcium homeostasis, because 1)
      calcium influx was increased in hypoxic cells, 2) hypoxia-induced osRb influx
      decrease was completely prevented by nifedipine (10-5 M), and 3) osRb influx
      decreased in normoxic cells incubated with ionomycin (10-6 M, 15 min).
      Furthermore, hypoxia-induced Na-K-ATPase impairment might be due, at least in
      part, to the endogenous release by hypoxic cells of a lipidic factor in
      extracellular medium, because incubation of normoxic cells with hypoxic cells
      conditioned medium (CM), or with the lipidic subphase from hypoxic cells CM, also
      induced a partial decrease in osRb influx. This decrease was associated with
      increased calcium influx into normoxic cells and was suppressed either by the
      removal of external calcium or by nifedipine, suggesting that the lipidic factor
      exerted its inhibitory action on Na-K-ATPase via an enhancement of calcium entry.
      These results indicate that prolonged hypoxic exposure impairs Na-K-ATPase
      activity in SV40 ATII cells and may therefore decrease the vectorial sodium
      transport by alveolar epithelium.

PMID- 8760135
TI  - Effect of dexamethasone on expression of adhesion molecules on CD4+ lymphocytes.
AB  - Despite the widespread use of corticosteroids in asthma therapy, little is known
      of the effects of corticosteroids on cell surface markers involved in T
      lymphocyte activation and adhesion. We used flow cytometry to analyze the effects
      of 1, 10, and 100 nM dexamethasone on expression of markers on resting and
      phytohemagglutinin (PHA)-stimulated peripheral blood CD4+ T lymphocytes.
      Expression of the leukocyte common antigen CD45 was significantly (P = 0.016, n =
      3) increased from an average mean fluorescence intensity of 215.8 [95% confidence
      intervals (CI): 100.5, 463.5] on cells from unstimulated cultures to 334.2 (CI:
      167.9, 663.7) on cells from PHA-stimulated cultures after 70-h incubation. At the
      same time, the percentage of cells also expressing the CD45RO isoform, a marker
      of memory T lymphocytes, increased significantly (P = 0.0006, n = 3) from 54.4 +/
      1.3% (unstimulated) to 92.8 +/- 0.6% (stimulated). Dexamethasone had no
      significant effect on expression of CD45 or CD45RO, including the observed
      changes. Dexamethasone also did not affect expression of the beta 1-integrin VLA
      4. These results suggest that corticosteroids do not modulate the cell surface
      expression of these molecules involved in CD4+ T lymphocyte activation, adhesion,
      and recirculation.

PMID- 8760136
TI  - Overexpression of R domain eliminates cAMP-stimulated Cl- secretion in 9/HTEo-
      cells in culture.
AB  - The intracellular hydrophilic region of the cystic fibrosis transmembrane
      conductance regulator (CFTR), the R domain, has been postulated to be a regulator
      of the Cl-channel. Under basal conditions R blocks the channel, but when
      phosphorylated, R undergoes conformational change to open the channel.
      Overexpression of R in 9/HTEo- cells, a human tracheal epithelial cell line with
      adenosine 3',5' -cyclic monophosphate (cAMP)-regulated Cl- conductance due to
      CFTR, caused reduced basal Cl- conductance and elimination of its response to
      isoproterenol, but ionomycin-stimulated Cl- efflux was preserved. Cells which
      overexpressed R showed no downregulation of endogenous CFTR mRNA and had normal
      cAMP production and protein kinase A (PKA) activity, so R did not act at these
      levels. Although the precise mechanism by which R affects CFTR conductance is
      undetermined, these cell lines could be useful in separating the cell biological
      consequences of impaired Cl- transport from those of mutant CFTR per se.

PMID- 8760137
TI  - Maximal PDGF-induced lung fibroblast chemotaxis requires PDGF receptor-alpha.
AB  - Alteration of the platelet-derived growth factor (PDGF) receptor system could be
      important in enhancing the mitogenic and chemotactic potential of lung
      fibroblasts during pulmonary fibrogenesis. We previously reported that
      interleukin-1 beta (IL-1 beta) upregulates the PDGF receptor-alpha (PDGFR-alpha)
      gene, and in this study we sought to establish the importance of the PDGFR-alpha
      relative to the PDGFR-beta in mediating a chemotactic response to PDGF-AA, -AB,
      and -BB. Pretreatment of fibroblasts for 24 h with IL-1 beta increased chemotaxis
      to all three PDGF isoforms. IL-1 beta pretreatment markedly increased the maximal
      number of 125I-labeled PDGF-AA binding sites but did not change the number of
      125I-PDGF-AB or PDGF-BB sites. However, IL-1 beta increased 125I-PDGFR-AB
      affinity twofold. Neomycin (5 mM) was used as a PDGFR-alpha antagonist and
      completely blocked 125I-PDGF-AA binding and PDGF-AA-induced chemotaxis. The
      binding affinity of 125I-PDGF-AB and 125I-PDGF-BB was increased two-to threefold
      by neomycin, and chemotaxis to PDGF-AB and PDGF-BB was enhanced. These results
      define a role for the PDGFR-alpha as a regulatory receptor subtype that is
      necessary for PDGF isoforms to exert maximal chemotaxis.

PMID- 8760138
TI  - Activation of KCa channels in airway smooth muscle cells by endogenous protein
      kinase A.
AB  - The regulation of calcium-activated potassium (KCa) channels by endogenous
      protein kinase A (PKA) was examined in inside-out patches from equine tracheal
      myocytes. In the absence of exogenous protein kinases, ATP (500 microM)
      significantly augmented KCa channel activity when applied to the cytosolic patch
      surface [open-state probability (nP0, mean +/- SE) increased from 0.010 +/- 0.001
      to 0.034 +/- 0.005 (n = 24)]. The stimulatory effect of ATP was mimicked by ATP
      gamma-S but not by AMP-PNP. Rather, AMP-PNP significantly inhibited channel
      activity. The PKA inhibitory peptide (PKI) significantly reduced nPo and
      prevented the augmenting effect of subsequent ATP. Ht 31, an inhibitory peptide
      for A-kinase-anchoring proteins (AKAP), but not its proline-substituted mutant,
      also blocked the stimulatory effect of ATP. These results suggest that 1) ATP
      augments KCa channel activity through phosphorylation; 2) the phosphorylation is
      catalyzed by endogenous PKA; 3) anchoring via AKAP is required to maintain
      association of PKA with the membrane; and 4) in a newly obtained patch, some of
      the KCa channels are probably already in a phosphorylated state.

PMID- 8760139
TI  - Protein kinase C in intracellular pH regulation in alveolar type II cells.
AB  - The Na+/H+ exchanger and Na(+)-HCO3- cotransporter have been implicated in
      regulation of intracellular pH (pHi) in alveolar type II cells. This study
      demonstrates that activation of protein kinase C (PKC) stimulates both of these
      ion transporters in type II cells. Treatment of type II cells with 80 nM phorbol
      12-myristate 13-acetate (PMA) increased the resting pHi in a time-dependent
      manner. Compared with control cells, the rates of recovery from an acid load
      increased with PMA treatment, reaching a maximum at 15 min, and returned to
      control levels by 3 h. The PMA-stimulated changes in recovery rate were sensitive
      to H-7, a PKC inhibitor. For PMA treatment up to 2 h, these recoveries were also
      sensitive to dimethylamiloride (DMA), an inhibitor of Na+/H+ exchanger activity,
      and to HCO3-, suggesting activation of both the Na+/H+ exchanger and the Na(+)
      HCO3- cotransporter. After prolonged (3 h) treatment with PMA, however, the
      recovery was insensitive to DMA but was sensitive to HCO3-, suggesting that the
      Na+/H+ exchanger was no longer active and that most of the recovery was mediated
      by the Na(+)-HCO3- cotransporter. PMA treatment also altered the Na+ kinetics of
      the recovery from an acid load with respect to the Michaelis constant (Km) and
      maximal ion flux (Vmax), suggesting protein modifications of each transporter. We
      suggest that PKC activation in type II cells results in acute and long-term
      changes in pHi regulatory mechanisms mediated by the Na+/H+ exchanger and by the
      Na(+)-HCO3- cotransporter.

PMID- 8760140
TI  - Augmentation of cytokine-induced nitric oxide synthesis by hydrogen peroxide.
AB  - The inducible isoform of nitric oxide synthase (iNOS) is induced upon stimulation
      of cells with cytokines and lipopolysaccharide (LPS). Stimulation of rat pleural
      mesothelial cells with combinations of interleukin-1 beta (IL-1 beta), tumor
      necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and LPS induced
      the synthesis of nitric oxide as measured by the oxidation products nitrite (NO2
      ) and nitrate (NO3-). Addition of 25-50 microM H2O2 to the cytokines
      significantly augmented the synthesis of NO2- and NO3-. Stimulation with IL-1
      beta and TNF-alpha plus H2O2 or IL-1 beta and LPS plus H2O2 increased the
      synthesis of NO2- and NO3- by 3.8- and 3.5-fold, respectively. These effects were
      inhibited by NG-nitro-L-arginine methyl ester and cycloheximide as well as by
      catalase. Immunoblotting demonstrated that H2O2 augmented cytokine-induced
      synthesis of iNOS protein. These effects were inhibited by certain antioxidants
      and metal chelators, suggesting that the hydroxyl radical may mediate the oxidant
      induced effect. Northern blotting demonstrated that H2O2 greatly augmented steady
      state levels of iNOS mRNA, suggesting that H2O2 acted in part at the
      transcriptional level.

PMID- 8760141
TI  - Role of calmodulin and myosin light-chain kinase in lung ischemia-reperfusion
      injury.
AB  - It is generally accepted that microvascular permeability is controlled by
      intercellular endothelial cell gap size. This process is controlled in
      endothelial cell monolayers and peripheral blood vessels by calmodulin (CaM)
      dependent myosin light-chain kinase (MLCK), which phosphorylates MLC20 with
      subsequent actin-myosin interaction. In the present study both CaM and MLCK
      blockers were studied during ischemia-reperfusion (I/R)-induced injury in
      isolated buffer-perfused rat lungs. The effects of a calcium ionophore (CaI) were
      tested in isolated intact rat lungs to compare the effects of increasing
      intracellular Ca2+ to I/R-induced damage. Because protein kinase C (PKC) could
      also be a mediator of I/R injury, a PKC inhibitor was studied in lungs subjected
      to either I/R or CaI. In lungs subjected to I/R alone, a fivefold increase in
      microvascular permeability occurred after 30 min of reperfusion (P < 0.001), and
      a tenfold increase was present after an additional 60 min of reperfusion (P <
      0.01). Pretreatment of the I/R lungs with a CaM inhibitor (trifluoperazine, 100
      microM) or with a MLCK inhibitor (ML-7,500 nM) blocked the microvascular damage
      at both 30 and 90 min of reperfusion. When the CaM inhibitor was introduced into
      the venous reservoir after 46 min of reperfusion, after the microvascular damage
      was present, no further increase in microvascular permeability occurred.
      Pretreatment of the lungs with a PKC inhibitor (staurosporine, 100 nM) did not
      alter the magnitude of the increased microvascular permeability produced by I/R
      or the time course of the damage. The calcium ionophore A23187 (7.5 microM)
      caused increases in Kfc values similar to those produced by I/R. Pretreatment of
      A23187-treated lungs with a CaM inhibitor produced no protective effect on the
      microvascular injury at 30 min after administration. Pretreatment of the CaI
      challenged lungs with staurosporine significantly increased the microvascular
      barrier injury at 30 min compared with that occurring with I/R. When a beta
      adrenergic receptor agonist (isoproterenol, 10 microM) was introduced to the lung
      after CaI-induced damage had occurred, no further increase in microvascular
      permeability was observed, and a trend toward reversal of injury occurred. We
      conclude from these studies that CaM/MLCK/MLC20 system is involved in our model
      of I/R-induced rat lung injury but is not involved in lung injury associated with
      Ca2+ entering the cell.

PMID- 8760142
TI  - Prostaglandin G/H synthase-2 is the constitutive and dominant isoform in cultured
      human lung epithelial cells.
AB  - Two isoforms of prostaglandin G/H synthase (PGHS; prostaglandin endoperoxide
      synthase, cyclooxygenase) have been identified; PGHS-1 is expressed
      constitutively in most tissues, whereas PGHS-2 is thought to be induced by
      various proinflammatory cytokines and growth factors. In this study, we
      determined which isoform of PGHS mRNA, protein, and activity was present
      constitutively in A549 (a human lung adenocarcinoma cell line) and in
      untransformed (normal human bronchial epithelial or NHBE) and transformed
      (16HBE4o-) human bronchial epithelial cells. Two PGHS-2-specific inhibitors, NS
      398 and L-745, 337, blocked the release of prostaglandin E2 from A549 cells with
      mean inhibitory concentrations of 5 and 18 nM, respectively, but did not inhibit
      its release from human bronchial smooth muscle cells (BSMC) at a concentration of
      10 microM. Northern and immunoblot analysis demonstrated that BSMC expressed PGHS
      1 mRNA and protein constitutively, whereas epithelial cells expressed PGHS-2 mRNA
      and protein constitutively with either undetectable (A549, 16HBE4o-) or very low
      levels (NHBE) of PGHS-1. We conclude that PGHS-2 is the dominant PGHS isoform in
      unstimulated and stimulated lung epithelial cells in culture.

PMID- 8760143
TI  - In vivo exposure to NO2 reduces TNF and IL-6 production by endotoxin-stimulated
      alveolar macrophages.
AB  - Exposure to NO2 appears to affect lung defense mechanisms. We exposed rats to 10
      ppm of NO2 for 24 h or 7 days and studied the production of tumor necrosis factor
      (TNF), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) by alveolar macrophages
      after endotoxin stimulation. TNF and IL-6 production was significantly decreased
      (four-to sixfold) in the cell lysate of alveolar macrophages isolated from rats
      exposed to NO2. In parallel, PGE2 production was significantly increased in the
      same samples and in the bronchoalveolar lavage fluid. Northern blot analysis of
      the two cytokines indicated a reduction of the mRNA content. We also studied the
      expression of the TNF receptor type 1 (TNF-R1), known to neutralize TNF activity
      in its soluble form, and found that expression of the mRNA was increased after
      endotoxin stimulation. We can conclude that rats exposed to NO2 produce less TNF
      and IL-6 and that this might be related to increased PGE2 production and
      increased expression of TNF-R1.

PMID- 8760144
TI  - Insulin-like growth factor-I and type I insulin-like growth factor receptor in
      85% O2-exposed rat lung.
AB  - The expression of insulin-like growth factor I (IGF-I) and insulin-like growth
      factor II (IGF-II) was studied in the lungs of adult rats exposed to air or 85%
      O2, using Northern analysis, in situ hybridization, and immunohistochemistry.
      Distribution of the type I insulin-like growth factor receptor (IGF-IR) was
      assessed by immunohistochemistry. IGF-I, but not IGF-II, was localized to airway
      epithelium, while IGF-IR was localized to perivascular and peribronchial cells,
      in the lungs of animals breathing air. IGF-II mRNA did not increase with exposure
      to 85% O2, but IGF-II was localized to sites of perivascular edema and to
      occasional peribronchial cells. A widespread increase in IGF-I mRNA and peptide
      was seen after both a 6-day and a 14-day exposure to O2, with maximal expression
      in the airway and alveolar epithelium, and lesser expression in interstitial
      cells. After 6 days in 85% O2, increased IGF-IR immunoreactivity was localized to
      both perivascular and peribronchial cells and to endothelial cells. By 14 days in
      85% O2, IGF-IR immunoreactivity was also localized to alveolar epithelial cells.
      The distribution of IGF-IR immunoreactivity was consistent with a paracrine role
      for IGF-I in O2-mediated pulmonary hypertension and airway hyperreactivity, by
      mediating smooth muscle cell hyperplasia, as well as a role in endothelial cell
      repair and late pneumocyte hyperplasia. The relative insensitivity of IGF-IR
      immunohistochemistry did not allow us to identify cells with low abundance IGF
      IR, and potential cellular targets for IGF-I actions after O2-exposure may be
      even more extensive than those recognized here.

PMID- 8760145
TI  - Redox regulation of manganese superoxide dismutase.
AB  - The importance of reactive oxygen species (ROS) or changes in cellular redox
      state in signal transduction and gene regulation is becoming increasingly
      evident. In this study, we tested the hypothesis that ROS are directly involved
      in the induction of the mitochondrial antioxidant manganese superoxide dismutase
      (MnSOD) and mediate the induction of MnSOD by tumor necrosis factor-alpha (TNF
      alpha). Pretreatment of human pulmonary adenocarcinoma cells H441 with the
      antioxidants N-acetyl-L-cysteine (NAC) and nordihydroguaiaretic acid (NDGA)
      blocked MnSOD induction by TNF-alpha, implicating ROS as a signaling agent in
      this pathway. Treatment of H441 cells with the exogenous oxidants hydrogen
      peroxide (H2O2) and diamide increased MnSOD mRNA, supporting the hypothesis that
      ROS directly affect expression of MnSOD. The temporal pattern of MnSOD induction
      differed for TNF-alpha and H2O2, suggesting distinct signaling pathways. DNA
      binding of two redox-sensitive transcription factors, NF-kappa B and activator
      protein (AP)-1, was evaluated. TNF-alpha increased nuclear factor (NF)-kappa B
      DNA binding, an effect blocked by pretreatment with NAC. H2O2 did not alter NF
      kappa B-DNA binding. There was no evidence of AP-1 binding in cells treated with
      either TNF-alpha or H2O2. We conclude that ROS directly alter MnSOD expression
      and are involved in the induction of MnSOD by TNF-alpha.

PMID- 8760146
TI  - Bioelectric response of human nasal epithelial cells to polycationic protein.
AB  - Polycationic proteins alter electrolyte transport by epithelium and endothelium,
      and in asthma are thought to disrupt the airway epithelium and contribute to
      hyperresponsiveness and airway plugging. In the present study, we used primary
      cultures of human nasal epithelial cells to investigate the response of
      respiratory tract epithelium to luminal presentation of a polycationic protein,
      protamine. Protamine (100 micrograms/ml) in the apical bathing solution had no
      significant effect on basal transepithelial resistance (Rt) but decreased short
      circuit current (Isc) and hyperpolarized the apical membrane, indicating that Na+
      absorption had been inhibited. Pretreating with amiloride inverted the response
      to protamine, resulting in an increase in Isc, depolarization of the apical
      membrane, and decrease in the fractional resistance of the apical membrane (fRa).
      The increase in Isc was inhibited by pretreatment with bumetanide. These results
      indicated that protamine augmented amiloride-induced Cl- secretion. Induction of
      Cl- secretion by bathing the apical surface in 3 mM Cl(-)-Ringer solution
      similarly resulted in protamine-induced depolarization of the apical membrane.
      Heparin precipitated protamine from solution and reversed the Isc responses. In
      summary, low concentrations of polycationic protein can alter electrolyte
      transport by human airway epithelium without desquamation, and the response is
      dependent on the secretory state of the tissue.

PMID- 8760147
TI  - Transcriptional regulation of iNOS by IL-1 beta in cultured rat pulmonary artery
      smooth muscle cells.
AB  - Transcriptional regulation of iNOS by IL-1 beta in cultured rat pulmonary artery
      smooth muscle cells. Am. J. Physiol. 271 (Lung Cell. Mol. Physiol. 15): L166
      L171, 1996.-Interleukin-1 beta (IL-1 beta) is the critical cytokine affecting
      peripheral vascular expression of inducible nitric oxide synthase (iNOS).
      Accordingly, we sought to determine a role for IL-1 beta in stimulating iNOS
      transcription in cultured rat pulmonary artery smooth muscle cells (RPASMC).
      Treatment of RPASMC with IL-1 beta caused a concentration-dependent increase in
      iNOS gene expression by Northern and Western blotting. To demonstrate IL-1 beta
      mediated transcriptional activation, we used transient liposome-mediated
      transfection of RPASMC with promoter-luciferase constructs containing deletional
      mutations of the murine macrophage iNOS 5' flanking promoter region. IL-1 beta
      increased promoter activity approximately two- to threefold over baseline in
      fragments ranging from -1592 (full-length) to -242 bp. Activity was lost,
      however, when the promoter fragment was shorter than -242 bp. IL-1 beta-mediated
      increases in steady-state iNOS mRNA were sensitive to pyrrolidine dithiocarbamate
      (PDTC), an inhibitor of NF-kappa B activation. Nuclear proteins from IL-1 beta
      stimulated cells demonstrated PDTC-sensitive binding to an oligonucleotide
      containing the sequence for the NF-kappa B binding element present in the region
      between -242 and -42 bp. These data document that IL-1 beta, by itself, increases
      iNOS expression in RPASMC by transcriptional activation, mediated in part by NF
      kappa B.

PMID- 8760148
TI  - Hypoxia impairs nitrovasodilator-induced pulmonary vasodilation: role of Na-K
      ATPase activity.
AB  - To elucidate the effect of hypoxia on nitrovasodilator-induced pulmonary
      vasodilation, we studied canine pulmonary arterial rings under isometric
      conditions in vitro. Exposure to hypoxia inhibited the relaxant responses of KCl
      contracted tissues to sodium nitroprusside (SNP), so that the maximal relaxation
      (Emax) and the negative logarithm of molar concentration required to produce 50%
      relaxation (pD2) were decreased from 92 +/- 7 to 62 +/- 5% and from 5.8 +/- 0.2
      to 4.7 +/- 0.3, respectively (means +/- SE, P < 0.01 for each). This effect was
      likewise observed when 8-bromoguanosine-3',5'-cyclic monophosphate was used as a
      relaxant. The impairment of SNP-induced relaxation of endothelium-denuded rings
      under hypoxia was abolished by ouabain or K(+)-free solution. Incubation with
      SNPincreased intracellular cGMP contents in a dose dependent manner, an effect
      that was not altered by hypoxia. SNP also increased ouabain-sensitive 86Rb
      uptake, and this effect was inhibited by hypoxia. These results suggest that
      hypoxia reduces nitrovasodilator-induced relaxation of pulmonary artery, probably
      through an inhibition of cGMP-dependent sarcolemmal Na-K-adenosine triphosphatase
      activity.

PMID- 8760149
TI  - Distribution of alveolar type II cells in neonatal and adult rat lung revealed by
      RT-PCR in situ.
AB  - Type II pneumocytes in newborn lungs are more uniformly distributed, whereas in
      adult lungs they are located at alveolar corners. We used morphometry and reverse
      transcription-polymerase chain reaction in situ hybridization of surfactant
      protein C mRNA to determine the patterns of type II cell distribution in random
      lung sections from Sprague-Dawley rats at various neonatal stages and adults.
      There was a progressive increase in the percentage of type II cells at alveolar
      corners from 30% at 1 day to 51, 62, 78, and 81% at 3, 5, and 7 days old and
      adult rats, respectively. There were statistically significant differences (P <
      0.001) in the localization of type II cells from the nearest alveolar corner in
      the 1-day-old compared with 7-day-old and adult rat lungs. These results show
      that rat type II cells localize to the alveolar corners within the first 7 days
      postnatally and provide a system for study of factors that regulate alveolar
      epithelial cell distribution.

PMID- 8760150
TI  - Effect of ACh and calmodulin inhibitor on O2 transfer from exocrine pancreatic
      microvessels of rats.
AB  - Effects of acetylcholine (ACh) and calmodulin (CaM) inhibitor, N-(6-aminohexyl)-5
      chloro-1-naphthalenesulfonamide hydrochloride (W-7), on the rate of O2 release
      (Ro2) from single exocrine pancreatic microvessels of anesthetized rats were
      investigated with dual-spot microspectroscopy. The surface of the pancreas was
      superfused with Krebs-Henseleit buffer containing various concentrations of ACh
      and/or W-7. Superfusion of ACh (> or = 20 microM) elevated Ro2 as well as
      pancreatic secretion approximately 2.5 times higher than that of control level,
      whereas superfusion of W-7 (> or = 100 microM) reduced approximately 50%. In both
      cases, O2 inflow in single microvessels, as quantified by oxyhemoglobin inflow
      into the microvessels, was maintained at control level. On the other hand,
      superfusion of both ACh and W-7 did not modify Ro2 and pancreatic secretion,
      despite significant reduction in O2 inflow. These results indicate that 1) the
      ACh-induced elevation of O2 release from single microvessels is accomplished by
      increased O2 extraction instead of increased O2 inflow in the microvessels, and
      2) the activity of a W-7-sensitive Ca2+ binding protein, most likely CaM, is
      responsible for half of the microvascular O2 transfer and of the pancreatic
      exocrine secretion.

PMID- 8760151
TI  - Effect of hypoxia on nitric oxide production in neonatal pig lung.
AB  - Nitric oxide (NO) synthase inhibitors potentiate hypoxic vasoconstriction (HV),
      suggesting that NO production during hypoxia normally acts to attenuate HV. To
      begin to examine the effect of hypoxia on lung NO production, we studied four
      groups of isolated neonatal pig lungs. In three groups of lungs, the accumulation
      of nitrite/nitrate (NOx-) was measured in the recirculating perfusate during
      ventilation with a control gas mixture (Cont), a hypoxic gas mixture (Hyp), or
      the control gas mixture with N omega-nitro-L-arginine methyl ester (L-NAME) added
      to the perfusate. Both hypoxia and L-NAME significantly increased perfusion
      pressure [pulmonary arterial pressure (Pa)-pulmonary venous pressure (Pv)]
      compared with control. NOx- accumulated in the perfusate at an average rate of
      9.1 +/- 2.3 (SE) nmol/min in Cont, 3.7 +/- 0.8 nmol/min (P < 0.05 vs. control) in
      Hyp, and 3.7 +/- 0.6 nmol/min (P < 0.05 vs. control) in L-NAME. In the fourth
      group of lungs, exhaled NO output was measured during ventilation with the
      control gas mixture, the hypoxic gas mixture, and the control gas mixture with L
      NAME added to the perfusate. Pa-Pv increased significantly with both hypoxia and
      L-NAME in these lungs. The exhaled NO output also decreased significantly with
      both hypoxia and L-NAME. These results suggest that in this preparation there was
      continuous production of NO that was decreased by hypoxia or L-NAME. It is not
      clear how the potentiation of HV by NO inhibitors and inhibition of NO production
      by hypoxia are linked.

PMID- 8760152
TI  - Sympathetic nerve activities in pulsatile and nonpulsatile systemic circulation
      in anesthetized goats.
AB  - To investigate the effects of pulsatile and nonpulsatile systemic circulation on
      the sympathetic nerve activity, using a left heart bypass technique, we converted
      systemic circulation between the pulsatile and the nonpulsatile mode in
      anesthetized goats and analyzed differences in periodicity and quantity of renal
      nerve activity (RNA). After pulsatile systemic circulation was converted to the
      nonpulsatile mode, the mean RNA was significantly increased from 10.7 +/- 3.6 to
      13.1 +/- 3.4 microV and periodic discharges of RNA, which corresponded to pulse
      related rhythm during pulsatile circulation, became obscure, whereas an 8-12
      cycle/s rhythm, which was distinguished and accounted for 30 +/- 9% of total
      intervals during pulsatile circulation, became dominant (48 +/- 11%). These
      results clarified a significant increase in mean RNA after depulsation of the
      systemic circulation and indicated that the cardiac-related rhythm in RNA could
      be produced by periodic inputs from arterial baroceptors alone, whereas the 8-12
      cycle/s rhythm that was present regardless of the type of circulation was the
      fundamental rhythm originating from the vasomotor center.

PMID- 8760153
TI  - KATP channels in rat heart: blockade of ischemic and acetylcholine-mediated
      preconditioning by glibenclamide.
AB  - The objective of this study was to examine if the opening of ATP-sensitive K+
      (KATP) channels play an important role in ischemic preconditioning (PC) in the
      rat heart. A second goal was to test the role of acetylcholine (ACh) in mimicking
      PC and test if it could be blocked by KATP antagonist. Glibenclamide, a specific
      antagonist of the KATP channel, was given as two doses of 0.3 mg/kg each at 60
      and 30 min before PC. Six groups of rats were subjected to ischemia and
      reperfusion (I/R) using these protocols: 1) control (I/R), 30-min ischemia
      followed by 90-min reperfusion (n = 6 rats); 2) preconditioned hearts given 5-min
      ischemia 10 min before I/R (n = 9 rats); 3) glibenclamide (0.3 mg/kg) treatment
      60 and 30 min before PC (n = 13 rats); 4) glibenclamide treatment before I/R (n =
      15 rats); 5) ACh infusion for 5 min (18 micrograms/ml) at a rate of 0.15 ml/min
      followed by equilibration for 10 min before I/R, n = 13 rats; and 6)
      glibenclamide treatment before ACh infusion followed by I/R (n = 11 rats).
      Preconditioning reduced the infarcted area (expressed as percent area at risk)
      from 42.0 +/- 4.4% in control to 8.7 +/- 6% (mean +/- SE, P < 0.05).
      Glibenclamide blocked the protection conferred by PC (39.1 +/- 4.5%, P < 0.05)
      without having a significant effect on control nonpreconditioned hearts. ACh
      infusion in lieu of PC also reduced infarct size to 25.0 +/- 5.63% (P < 0.05
      compared with control), which was again blocked by glibenclamide (44.2 +/- 5.0%,
      P < 0.05). The data suggest that opening of KATP channels for ischemic and ACh
      mediated preconditioning is also important in the rat heart.

PMID- 8760155
TI  - Muscle reflex stimulates sympathetic postganglionic efferents innervating triceps
      surae muscles of cats.
AB  - Two neural mechanisms contribute to the cardiovascular responses to exercise. The
      first, central command, proposes a parallel activation of central locomotor and
      brain stem circuits controlling cardiovascular function. The second, the muscle
      reflex, proposes that contraction-activated group III and IV afferents increase
      cardiovascular function. In humans, whole nerve recordings of sympathetic
      discharge suggest that central command increases sympathetic outflow to skin but
      not to skeletal muscle and that the muscle reflex increases sympathetic outflow
      to skeletal muscle but not to skin. We therefore tested the hypothesis that the
      muscle reflex, but not central command, increases the discharge of single
      sympathetic postganglionic efferents innervating the triceps surae muscles of
      decerebrate unanesthetized cats. Central command was evoked by electrical
      stimulation of the mesencephalic locomotor region. The reflex was evoked by
      electrical stimulation of the tibial nerve, which in turn contracted the triceps
      surae muscles. Hexamethonium abolished spontaneous and evoked activity, verifying
      that the recordings were from sympathetic postganglionic fibers. The discharge of
      13 efferents was increased by static contraction (from 0.6 +/- 0.2 to 1.0 +/- 0.3
      imp/s; P < 0.05) but was not increased by central command (from 0.6 +/- 0.2 to
      0.8 +/- 0.2 imp/s; P > 0.05). Nevertheless, the discharge of nine efferents, not
      increased by central command before alpha-adrenergic blockade (from 0.5 +/- 0.2
      to 0.9 +/- 0.4 imp/s; P > 0.05), was increased after blockade (from 1.3 +/- 0.2
      to 3.2 +/- 0.8 imp/s; P < 0.05). We conclude that the muscle reflex stimulates
      sympathetic postganglionic efferents innervating the vasculature of skeletal
      muscle. Furthermore, baroreceptors appear to buffer the central command-induced
      increases in the discharge of these efferents.

PMID- 8760154
TI  - Comparative effects of contraction and angiotensin II on growth of adult feline
      cardiocytes in primary culture.
AB  - The purposes of this study were 1) to determine whether angiotensin II causes
      growth of adult feline cardiocytes in long-term culture, 2) to compare the growth
      effects of angiotensin II with those resulting from electrically stimulated
      contraction, and 3) to determine whether the anabolic effects of contraction are
      exerted via the angiotensin type 1 receptor. Adult feline cardiocytes were
      cultured on laminin-coated trays in a serum-free medium. Cardiocytes were either
      electrically stimulated to contract (1 Hz, 5-ms pulse duration, alternating
      polarity) or were nonstimulated and quiescent. Quiescent cells were studied as
      controls and after treatment with angiotensin II (10(-8) M), losartan (10(-6) M;
      an angiotensin type 1-receptor antagonist), or angiotensin II plus losartan.
      Contracting cells were studied in the presence and absence of angiotensin II or
      losartan. In quiescent cardiocytes, angiotensin II treatment on day 7
      significantly increased protein synthesis rates by 22% and protein content per
      cell by 17%. The effects of angiotensin II were completely blocked by losartan.
      Electrically stimulated contraction on days 4 and 7 in culture significantly
      increased protein synthesis rate by 18 and 38% and protein content per cell by 19
      and 46%, respectively. Angiotensin II treatment did not further increase protein
      synthesis rate or protein content in contracting cardiocytes. Furthermore,
      losartan did not block the anabolic effects of contraction on protein synthesis
      rates or protein content. In conclusion, angiotensin II can exert a modest
      anabolic effect on adult feline cardiocytes in culture. In contracting feline
      cardiocytes, angiotensin II has no effect on growth. Growth caused by
      electrically stimulated contraction occurs more rapidly and is greater in
      magnitude than that caused by angiotensin II. Growth of contracting adult feline
      cardiocytes is not dependent on activation of the angiotensin receptor.

PMID- 8760156
TI  - Parasympathetic inhibition of sympathetic effects on sinus rate in anesthetized
      dogs.
AB  - The intracardiac parasympathetic neural elements that control sinus rate are
      found in the fatty tissue overlying the atrial junctions of the right pulmonary
      veins of mammalian hearts. We refer to these nerves as the sinus rate-related
      parasympathetic nerves (SRRPN). Thus, to elucidate the role of SRRPN, we studied
      the effects of cervical vagus stimulation on the positive chronotropic responses
      to cardiac sympathetic nerve stimulation and isoproterenol infusion before and
      after the SRRPN were removed in the open-chest anesthetized dog heart. Before
      SRRPN denervation, cervical vagus stimulation suppressed the sinus rate and the
      positive chronotropic response to sympathetic nerve stimulation or isoproterenol
      infusion. After SRRPN denervation, cervical vagus stimulation hardly decreased
      the sinus rate. On the other hand, even after SRRPN denervation, cervical vagus
      stimulation suppressed the rate increased by sympathetic stimulation. Cervical
      vagus stimulation also attenuated the sinus rate increased by isoproterenol. The
      inhibition by vagus stimulation of the chronotropic response to sympathetic
      stimulation was greater than that of the response to isoproterenol. The
      attenuation by cervical vagus stimulation was abolished by atropine. These
      results suggest that 1) a small number of vagus nerves to the sinoatrial nodal
      area different from the SRRPN decrease the sinus rate increased by adrenergic
      interventions and 2) the same activation that causes relatively small effects on
      sinus rate is capable of causing much larger changes in sinus rate during
      increased sympathetic tone or in the case of beta-adrenoceptor agonist treatment
      in the heart in situ.

PMID- 8760157
TI  - Functional effects of EMD-57033 in isovolumically beating isolated rabbit hearts.
AB  - The results of isolated myocyte and cardiac muscle experiments indicate that
      inotropic agents that increase responsiveness of myofilaments to Ca2+ (so-called
      Ca2+ sensitizers) may prolong myocardial contraction and increase diastolic tone,
      but the importance of these effects in the whole heart is unclear. Therefore, we
      studied the effects of the Ca2+ sensitizer EMD-57033 (EMD) on left ventricular
      (LV) contractile events and passive properties in isovolumically beating isolated
      rabbit hearts that were buffer perfused at 30 degrees C. Several LV pressure and
      timing variables were evaluated, including the passive pressure-volume
      relationship, the Frank-Starling relationship, and the wall stress dependence of
      the duration of relaxation during perfusion with 0, 2, and 4 microM EMD. EMD (2
      microM) increased average peak developed pressure of the Frank-Starling
      relationship by approximately 18%. In contrast, the peak developed pressure of
      the Frank-Starling relationship decreased toward control with 4 microM EMD, and
      therefore all the results presented pertain to 2 microM EMD. The maximum
      developed pressure at baseline volume was increased by approximately 19% by 2
      microM EMD, and this was accompanied by an increase in contraction duration of
      approximately 13%, due exclusively to slowed relaxation. The relative
      contributions of maximal wall stress (sigma max) versus an independent negative
      lusitropic effect of EMD were determined at three LV volumes. At baseline volume,
      just less than one-half of the effect to slow relaxation was ascribable to an
      increase in sigma max, whereas the remainder was due to an independent EMD
      effect. LV passive properties were unchanged by perfusion with 2 microM EMD. We
      conclude that EMD is a potent inotrope in our isolated rabbit heart preparation,
      which has no effect on diastolic tone and causes a modest prolongation of
      contraction duration due to slowed relaxation. At baseline volume, approximately
      50% of the slowed relaxation was ascribable to positive inotropy leading to
      increased sigma max, whereas the remaining approximately 50% was ascribable to a
      direct negative lusitropic effect of EMD. We discuss our results in terms of the
      current hypotheses regarding the mechanism of action of the Ca2+ sensitizers.

PMID- 8760158
TI  - Perfusion-MVO2 mismatch during inotropic stress in CAD patients with normal
      contractile function.
AB  - With the use of[11C]acetate, positron emission tomography (PET) permits
      exploration of myocardial blood flow (MBF) and oxidative metabolism (MVo2)
      coupling. PET imaging was performed at rest and under dobutamine infusion in 8
      normal subjects and 10 coronary artery disease (CAD) patients with significant
      single-vessel left anterior descending (LAD) stenosis (> 70%) and normal regional
      left contractile function at rest. Resting MBF and MVo2 were similar in remote
      and LAD regions of normal subjects and patients. During dobutamine infusion, MBF
      and myocardial flow reserve were lower in LAD regions of patients compared with
      remote regions (MBF: 1.49 +/- 0.42 and 2.06 +/- 0.57 ml.g-1.min-1, P < 0.01;
      reserve: 1.73 +/- 0.59 and 2.14 +/- 0.47, P < 0.01, respectively), whereas MVo2
      expressed as kmono (an index of MVo2) and metabolic reserve were similar (kmono:
      0.106 +/- 0.021 vs. 0.107 +/- 0.017 min-1; reserve: 1.88 +/- 0.32 vs. 1.98 +/-
      0.37, respectively). This is the first human study showing that, in normal
      contractile regions at rest but perfused by stenosed artery, a disparate rise in
      MVo2 relative to the rise in myocardial perfusion occurs during increased cardiac
      work induced by dobutamine. This flow-metabolism uncoupling probably reflects an
      increase in O2 extraction.

PMID- 8760159
TI  - SERCA2a and mitochondrial cytochrome oxidase expression are increased in hearts
      of exercise-trained old rats.
AB  - Aging of rats results in slower activities of calcium transport by cardiac
      calcium adenosinetriphosphatase (ATPase) of the sarcoplasmic reticulum (SR) and
      mitochondrial cytochrome oxidase (COX). These enzyme activities are faster after
      exercise training of previously sedentary old rats. Our purpose was to determine
      whether the expression of the genes encoding SR calcium ATPase (SERCA2a) or COX
      is altered by exercise training. Old (24-mo-old) male Fischer 344 rats were
      assigned to SO (sedentary old) or EO (exercised old) groups and compared with
      younger (12-mo-old) sedentary rats (SM). EO rats were trained on a treadmill for
      8-10 wk. SERCA2a and COX mRNAs were lower (P < 0.05) in SO compared with SM and
      EO, whereas glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and cardiac alpha
      actin mRNAs were similar across groups. The immunoreactive protein contents of
      cardiac calcium ATPase, cytochrome c, sarcomeric actin, and GAPDH followed the
      changes, when observed, in mRNA contents. Thus pretranslational mechanisms may be
      modified in some genes during aging and exercise training of previously sedentary
      old rats.

PMID- 8760160
TI  - Right ventricular contractile protein function in rats with left ventricular
      myocardial infarction.
AB  - We studied contractile function in cardiac trabeculae isolated from the right
      ventricles (RV) of rats with experimental heart failure (HF) induced by left
      ventricular (LV) myocardial infarction (24 wk post-MI; n = 6) and from sham
      operated rats (n = 7). Sarcomere length (SL) was measured by laser diffraction
      techniques, and force (F) was measured by silicon strain gauge. SL was kept
      constant at all times by computer feedback control. HF was associated with marked
      LV dilation and pulmonary congestion. In intact, RV twitching trabeculae, HF was
      associated with a depression of the F-SL relation at extracellular Ca2+
      concentration ([Ca2+]o) = 1.5 mM and a depression of the F-[Ca2+]o relation at SL
      = 2.0 microns. HF was also associated with a significant depression of the F
      intracellular [Ca2+] relation at SL = 2.0 microns measured after chemical
      permeabilization of these RV trabeculae (skinned fibers). Our results suggest
      that reduced force development in this model of HF is due, in part, to depressed
      function of the contractile filaments.

PMID- 8760161
TI  - Stimulation of 5-HT3 receptors in the NTS inhibits the cardiac Bezold-Jarisch
      reflex response.
AB  - Intra-atrial administration of phenylbiguanide has been shown to trigger, through
      the stimulation of vagal afferent C-fibers, reflex bradycardia, hypotension, and
      sympathoinhibition classically known as the Bezold-Jarisch (B-J) reflex (O.
      Krayer. Naunyn-Schmiedeberg's Arch. Exp. Pathol. Pharmacol. 240: 361-368, 1961).
      The effects of microinjections, into the nucleus tractus solitarius (NTS), of
      serotonin (5-HT) and 1-(m-chlorophenyl)-biguanide (CPBG), a potent 5-HT3 receptor
      agonist, on these reflex responses were studied in urethananesthetized rats. 5-HT
      (600 and 900 pmol) and CPBG (10-150 pmol) produced a dose-dependent inhibition of
      the atropine-sensitive bradycardiac component of the B-J reflex. The effect of
      both agonists was reversed by prior local microinjection of the 5-HT3 receptor
      antagonists zacopride (100 pmol) and ondansetron (100 pmol), but not by that of
      the 5-HT2 receptor antagonist ketanserin (10 pmol) or the mixed 5-HT1/5-HT2
      receptor antagonist methysergide (100 pmol). In contrast, CPBG (150 pmol) did not
      affect the B-J reflex inhibition of lumbar sympathetic nerve discharge. These
      results show that stimulation of NTS 5-HT3 receptors produced an inhibition of
      the cardiovagal component of the B-J reflex without affecting its sympathetic
      component. Because the stimulation of these receptors also inhibits the cardiac
      component of the baroreflex, the present data suggest the participation of NTS 5
      HT3 receptors in the mechanisms that modulate cardiac reflex responses elicited
      by messages from different vagal afferents.

PMID- 8760162
TI  - Effect of endothelin antagonism on blood pressure and vascular structure in
      renovascular hypertensive rats.
AB  - To investigate the potential pathogenic role of endothelin in blood pressure
      elevation and vascular hypertrophy in renovascular hypertensive rats, which
      present twofold elevations in endothelin-1 mRNA abundance in blood vessels, the
      response of blood pressure and vascular structure to chronic treatment with the
      endothelin receptor antagonist bosentan was evaluated. One-kidney, one clip
      (1K,1C) and two kidney, one clip (2K,1C) Goldblatt hypertensive rats were treated
      for 2 wk with bosentan (100 mg.kg-1.day-1) in their chow, and systolic blood
      pressure was measured by the tail-cuff method. Vascular structure was studied in
      small arteries mounted on a wire myograph. Treatment with bosentan did not result
      in a significant change in systolic blood pressure or in the structure of small
      coronary, renal cortical, mesenteric, or femoral arteries in 1K, 1C or in 2K, 1C
      hypertensive rats. In conclusion, modest (twofold) elevations of endothelin-1
      gene expression in blood vessels in renovascular hypertension are not associated
      with hypotensive responses or regression of vascular hypertrophy during treatment
      with endothelin antagonists in contrast to what is found in deoxycorticosterone
      acetate salt hypertensive rats, which exhibit very dramatic increases in
      endothelin-1 expression (five-to eightfold) and do respond to endothelin
      antagonism with blood pressure lowering and regression of vascular hypertrophy.
      These small elevations of vascular endothelin-1 gene expression thus do not
      appear to indicate the presence of an endothelin component in blood pressure
      elevation in renovascular hypertension in rats.

PMID- 8760163
TI  - Volume-related activities of sodium ion transporters: multinuclear NMR studies of
      isolated rat hearts.
AB  - The present study aims to determine the volume-related activities of sodium ion
      transporters in the rat heart. Intracellular volumes were measured in isolated
      hearts by 1H of water and 59Co nuclear magnetic resonance (NMR) of the
      extracellular marker cobalticyanide. Inhibition of the Na-K
      adenosinetriphosphatase pumps with 50 microM ouabain did not affect the extent of
      cellular swelling during 30 min of ischemia: cells swelled by 0.37 ml/g dry wt
      compared with the controls (0.38 ml/g dry wt). After perfusion with 400 microM
      ouabain or 200 microM iodoacetate, the cells shrank during ischemia (from 2.50 +/
      0.06 to 2.20 +/- 0.09 and 2.28 +/- 0.07 ml/g dry wt, respectively). Inhibition
      of passive sodium ion transporters reduced cellular swelling during ischemia:
      pretreatment (10 min) with 100 microM furosemide (Na-K-2Cl cotransport), 1.5
      microM ethylisopropylamiloride (Na/H antiport), and 50 microM lidocaine (sodium
      channels) led to swelling of 0.27, 0.21, and 0.13 ml/g dry wt, respectively. The
      extent of cellular water accumulation was apparently correlated with the onset
      and maximal force of the ischemic contracture, unlike the data of hearts treated
      with ouabain and iodoacetate. The blockage of each of the passive sodium
      transporters improved the recovery of intracellular volumes at reperfusion,
      indicating that in the heart these pathways are responsible for the sustained
      reperfusion cellular edema. It is concluded that acute cellular swelling during
      myocardial ischemia is not caused by insufficiency of the Na-K pumps but is
      partially mediated by systems that transport sodium into the cells.

PMID- 8760164
TI  - Blockade of brain "ouabain" prevents sympathoexcitatory and pressor responses to
      high sodium in SHR.
AB  - The effects of blockade of brain "ouabain" by central infusion of antibody Fab
      fragments, which bind ouabain and brain "ouabain" with high affinity, on sodium
      sensitive hypertension were studied in spontaneously hypertensive rats (SHR) from
      5 to 9 wk of age on high- or regular sodium diet. The Fab fragments or, in
      controls, gamma-globulins were infused intracerebroventricularly via osmotic
      minipump. Blood pressure (BP), heart rate (HR), and renal sympathetic nerve
      activity (RSNA) and their responses to air stress and to the alpha 2-adrenoceptor
      agonist guanabenz intracerebroventricularly were recorded in conscious rats at 9
      wk. In control SHR but not Wistar-Kyoto rats (WKY), high sodium further increased
      resting mean arterial pressure (171 +/- 3 vs. 141 +/- 4 mmHg in control SHR on
      regular sodium) and potentiated excitatory and inhibitory responses of BP, HR,
      and RSNA to air stress and intracerebroventricular guanabenz, respectively. These
      effects of high sodium were all prevented by intracerebroventricular Fab
      fragments. In SHR on regular sodium or WKY on either diet, the Fab fragments had
      no effects on resting BP or responses to air stress and guanabenz. We conclude
      that similar to Dahl salt-sensitive rats, in SHR, a sodium-induced increase in
      brain "ouabain" is responsible for the decreased sympathoinhibition and increased
      sympathoexcitation and thus the exacerbation of hypertension. Brain "ouabain"
      appears not to be involved in the development of hypertension in SHR on regular
      sodium intake.

PMID- 8760165
TI  - Protein kinase C inhibits delayed rectifier K+ current in rabbit vascular smooth
      muscle cells.
AB  - The effect of protein kinase C (PKC) activation on 4-aminopyridine (4-AP)
      sensitive delayed rectifier current (IdK) was studied in isolated rabbit portal
      vein smooth muscle cells by use of standard whole cell voltage clamp. The effects
      of the phorbol ester, 4 beta-phorbol 12,13-dibutyrate (PdBu, 100 nM) and
      diacylglycerol analogues, 1,2-dioctanoyl-sn-glycerol (1,2-diC8, 10 microM) and
      1,3-dioctanoyl-sn-glycerol (1,3-diC8, 10 microM), on macroscopic whole cell IdK
      were assessed in myocytes dialyzed with 10 mM 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid (BAPTA) and 5 mM ATP (20-22 degrees C). Activation of
      PKC by 1,2-diC8 or PdBu caused a decline in IdK that was reversed with washout of
      drug. 1,2-diC8 had no effect on outward current present after exposure to 4-AP
      (20 mM). The inactive analogue, 1,3-diC8, did not affect IdK, but subsequent
      exposure to the active analogue, 1,2-diC8, caused a marked depression of the
      current. The inhibition of IdK by 1,2-diC8 was significantly reduced by
      intracellular dialysis with the inhibitors of PKC, chelerythrine (50 microM) and
      calphostin C (1 microM). Substitution of extracellular Ca2+ with Mg2+ in the
      presence of 10 mM intracellular BAPTA did not affect the suppression of IdK by
      1,2-diC8, indicating the involvement of a Ca(2+)-independent isoform of PKC. This
      study suggests a novel signal transduction mechanism for inhibition of 4-AP
      sensitive IdK involving a phosphotransferase reaction catalyzed by PKC in
      vascular smooth muscle myocytes.

PMID- 8760166
TI  - Regulation of ANG II receptor in hypertension: role of ANG II.
AB  - To investigate the role of angiotensin II (ANG II) in the development of
      hypertension induced by reduced renal mass (RRM) and the gene expression of ANG
      II type 1 (AT1) receptors in the remnant renal tissue, four groups of rats were
      given 1% NaCl in water and subjected to RRM, RRM+ ramipril, RRM+ losartan, or
      sham surgery (control). Tail-cuff systolic blood pressure was significantly
      higher in RRM rats than in the other three groups. Northern blot showed that AT1
      gene expression was significantly decreased in RRM, RRM + ramipril, or RRM +
      losartan vs. control. There was no significant difference among the three RRM
      groups. Renal transforming growth factor-beta 1 (TGF-beta 1) mRNA levels were
      increased threefold (P < 0.05) in RRM, RRM+ ramipril, and RRM+ losartan vs.
      control. There was no significant difference among the three RRM groups. We
      conclude that the development of RRM hypertension is ANG II dependent but not
      mediated by AT1 gene expression. RRM downregulates AT1 mRNA and upregulates TGF
      beta 1 mRNA in the remnant renal tissue, regardless of blood pressure or plasma
      levels of ANG II, suggesting that these gene responses are triggered by an effect
      of local injury.

PMID- 8760167
TI  - Effect of subarachnoid hemorrhage on dilatation of rat basilar artery in vivo.
AB  - Cerebral vasodilator responses are often impaired following subarachnoid
      hemorrhage (SAH). Because depolarization of vascular muscle may occur after SAH,
      we tested in vivo the hypothesis that SAH may augment dilatation in response to
      hyperpolarization due to activation of K+ channels. Anesthetized rats were
      studied two days after injection of saline or autologous blood into the cisterna
      magna. Diameter of the basilar artery in vivo was 224 +/- 5 microns (mean +/- SE)
      in saline-treated rats and 201 +/- 6 microns in SAH rats (P < 0.05). In control
      rats, acetylcholine (ACh), sodium nitroprusside (SNP), aprikalim and calcitonin
      gene-related peptide (CGRP; both activators of ATP-sensitive K+ channels),
      papaverine, 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP), and brain
      natriuretic peptide (BNP; an activator of particulate guanylate cyclase) produced
      concentration-dependent dilatation. In SAH rats, vasodilatation was impaired in
      response to ACh and SNP. In contrast, vasodilator responses to aprikalim and CGRP
      were augmented in SAH, rats (by two- to fourfold). Vasodilator responses to 8
      BrcGMP, papaverine, and BNP were similar in both groups. Thus responses mediated
      by activation of soluble guanylate cyclase are selectively impaired by SAH, but
      responses to guanosine 3',5'-cyclic monophosphate are normal. Vasodilator
      responses to activation of ATP-sensitive K+ channels are augmented by SAH.

PMID- 8760168
TI  - Nitric oxide regulates endothelium-dependent vasodilator responses in rabbit
      hindquarters vascular bed in vivo.
AB  - The objective of this study was to determine whether nitric oxide (NO) could
      function as a negative feedback modulator of endothelium-dependent vasodilation
      in vivo. To this end, the influence of exogenous NO on vasodilator responses in
      the rabbit hindquarters vascular bed was determined. Previous in vitro studies
      have demonstrated that NO inhibits both neuronal NO synthase from rat cerebellum
      as well as NO synthase derived from bovine aortic endothelial cells. The present
      study was conducted in the rabbit hindquarters vascular bed under conditions of
      constant blood flow so that changes in pressure directly reflected changes in
      vascular resistance. Under these in vivo conditions, the NO donor agent S-nitroso
      N-acetylpenicillamine (SNAP) reversibly attenuated responses to the endothelium
      dependent vasodilators, acetylcholine and bradykinin. In contrast, SNAP did not
      influence the endothelium-independent vasodilator response to SNAP itself or to 8
      bromoguanosine 3',5'-cyclic monophosphate. These observations indicate clearly
      that NO interferes with endothelium-dependent vasodilator action and support the
      view that endogenous NO may actually play a physiological role in regulating
      vascular tone.

PMID- 8760169
TI  - Different responses of epicardium and endocardium to KATP channel modulators
      during regional ischemia.
AB  - We examined the responses of epicardial (Epi) and endocardial (Endo) layers to
      ATP-sensitive K+ (KATP) channel modulators during regional ischemia in
      anesthetized dogs. Five-minute occlusion of the left anterior descending coronary
      artery was repeated at 30-min interval. Monophasic action potentials (MAPs) and
      extracellular K+ concentrations ([K+]o) were measured at Epi and Endo layers. 5
      Hydroxydecanoate (5-HD, 30 mg/kg iv), a KATP channel blocker, or nicorandil (NCR,
      0.2-0.5 mg/kg iv), an opener, was administered before the third or fourth
      occlusion. Shortening rate of action potential duration at 90% repolarization
      (APD90) was greater at the Epi layer than at the Endo layer during the first 4
      min after the second control occlusion (19.7 +/- 1.5 vs. 13.1 +/- 2.4%, n = 14, P
      < 0.05). 5-HD suppressed the shortening preferentially at the Epi layer and
      reduced the difference between the two layers (11.0 +/- 3.5 vs. 11.5 +/- 3.7%, n
      = 6, NS). In contrast, NCR augmented the shortening preferentially at the Epi
      layer and increased the difference between the two layers at 4 min (29.0 +/- 2.0
      vs. 5.9 +/- 3.0%, n = 6, P < 0.05). The time differentiation of [K+]o rise was
      similar at the two layers during the control occlusion (0.44 vs. 0.50 mM/min, n =
      12). 5-HD reduced the rate of [K+]o rise at both layers (0.34 vs. 0.40 mM/min),
      whereas NCR augmented the rate at the Epi layer (0.82 vs. 0.50 mM/min).
      Activation of KATP channels appears to be involved in ischemia-induced APD
      shortening and [K+]o rise. The different responses of the two layers suggest a
      lower threshold for activation and/or a denser distribution of KATP channels or
      other K+ channels at the Epi layer.

PMID- 8760170
TI  - Regional and functional factors determining induction and maintenance of atrial
      fibrillation in dogs.
AB  - The present study was designed to determine the factors governing the ability of
      premature beats at various atrial sites to initiate atrial fibrillation (AF) and
      the determinants of the duration of AF in dogs at 1-10 Hz. The site of atrial
      extrasystoles determined their ability to induce AF. Regional differences in AF
      inducibility were due to differences in local refractoriness. Premature beats
      initiated AF by blocking in regions of greater refractoriness, causing
      macroreentrant activation with subsequent disorganization producing fibrillation.
      The atrial refractory period and wavelength during rapid 1:1 atrial pacing were
      weak predictors of AF duration (r = 0.24 and 0.23, respectively), which depended
      strongly on variability in regional refractoriness measured by the standard
      deviation in local refractory periods (r = 0.80, P < 0.001) and on the
      heterogeneity of activation during AF (r = 0.74, P < 0.001). Thus, premature
      beats cause AF by initiating a single macroreentrant cycle that degenerates into
      multiple wavefronts, regional refractoriness is the primary determinant of AF
      induction by premature beats, and variability in refractoriness may be an
      important determinant of the ability of AF to sustain itself.

PMID- 8760172
TI  - cGMP and cAMP in prostaglandin-induced pial artery dilation and increased CSF
      opioid concentration.
AB  - It has been observed that prostaglandins (PG) PGE2 and PGI2 increased cortical
      periarachnoid cerebrospinal fluid (CSF) methionine enkephalin (Met-enk) and
      leucine enkephalin (Leu-enk) concentrations in the newborn pig. It was also
      observed that PG-induced pial artery dilation was associated with elevated CSF
      guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic
      monophosphate (cAMP) levels in the piglet. However, other studies have not always
      supported a role for cGMP in PG dilation. The present study used a
      pharmacological approach to test the hypothesis that both cGMP and cAMP
      contribute to PG-induced pial dilation and associated elevated CSF opioid
      concentration. PGE2 produced pial vasodilation that was blunted by the Rp
      diastereomer of bromoguanosine 3',5'-cyclic monophosphothioate [Rp-8-BrcGMPS (10(
      5)M)], a cGMP antagonist (9 +/- 1, 16 +/- 1, and 23 +/- 1 vs. 4 +/- 1, 6 +/- 1,
      and 9 +/- 1% for 1, 10, and 100 ng/ml PGE2 before and after Rp-8-BrcGMPS,
      respectively). PGE2 elevated CSF Met-enk concentration, and these biochemical
      changes were also blunted by Rp-8-BrcGMPS (1,001 +/- 23, 1,424 +/- 54, and 1,973
      +/- 56 vs. 804 +/- 41, 988 +/- 52, and 1,222 +/- 21 pg/ml for control, 10, and
      100 ng/ml PGE2 in the absence and presence of Rp-8-BrcGMPS, respectively).
      Similar biochemical and vascular effects of Rp-8-BrcGMPS were observed for PGI2.
      Additionally, the Rp diastereomer of bromoadenosine 3',5'-cyclic
      monophosphothioate [Rp-8-BrcAMPS (10(-5)M)], a cAMP antagonist, blunted PGE2
      dilation (10 +/- 1, 15 +/- 1, and 24 +/- 1 vs. 5 +/- 1, 8 +/- 1, and 12 +/- 1%
      for 1, 10, and 100 ng/ml PGE2 before and after Rp-8-BrcAMPS, respectively). PGE2
      associated increases in CSF Met-enk and Leu-enk were similarly blunted by Rp-8
      BrcAMPS. These data show that both cGMP and cAMP contribute to PG-induced pial
      dilation and that PG-associated elevated CSF cGMP and cAMP levels result in
      increased CSF Met-enk and Leu-enk concentration.

PMID- 8760171
TI  - Formation of an F2-isoprostane in vascular smooth muscle cells by elevated
      glucose and growth factors.
AB  - Recently a series of non-cyclooxygenase-derived prostanoids were identified in
      vivo in humans and in animal models of free radical injury as products of free
      radical-catalyzed peroxidation of arachidonic acid. One of these, an F2
      isoprostane, 8-epiprostaglandin F2 alpha (8-epi-PGF 2 alpha), is a potent renal
      vasoconstrictor and can increase vascular smooth muscle cell (VSMC) DNA
      synthesis. In the present study we have evaluated whether F2-isoprostanes play a
      role in diabetic vascular dysfunction by studying the formation of 8-epi-PGF2
      alpha in porcine VSMC (PVSMC) cultured under hyperglycemic conditions. 8-Epi-PGF2
      alpha levels were quantitated by a specific enzyme immunoassay. We also examined
      whether certain VSMC growth factors, such as angiotensin II, platelet-derived
      growth factor, and transforming growth factor-beta, could also regulate the
      formation of 8-epi-PGF2 alpha. We observed that PVSMC cultured under high glucose
      (HG) conditions produced significantly higher amounts of 8-epi-PGF2 alpha
      compared with normal glucose (NG) conditions (3.7 +/- 0.13 ng/10(6) cells in HG
      vs. 2.9 +/- 0.2 ng/10(6) cells in NG, P < 0.05). Furthermore, all three growth
      factors tested evoked significant dose-dependent formation of 8-epi-PGF2 alpha
      (ranging from 125 to 220% of control). These results suggest that 8-epi-PGF2
      alpha formation, as a result of hyperglycemia or due to growth factor action, may
      lead to increased VSMC growth and contribute to the complications of diabetes and
      cardiovascular disease.

PMID- 8760173
TI  - Lymph pump mechanics in the rabbit hind leg.
AB  - The mechanisms that govern fluid uptake by the initial lymphatics and adjustment
      of lymph flow rates remain to a large degree uncertain. The aim of this study was
      to examine how passive tissue movement contributes to lymph flow rates. Lymph
      fluid was collected via a cannula inserted into one of the popliteal prenodal
      lymphatics in the rabbit hind leg. Lymph flow rates were measured during periodic
      whole leg rotation and controlled oscillatory massage of the dorsal skin of the
      foot. Without whole leg rotation, lymph flow remained at low values (< 0.01
      ml/h). Introduction of whole leg passive rotation caused a frequency-dependent
      increase in lymph flow rates, which were increased linearly with the log of
      frequency between 0.03 and 1.0 Hz. Local skin massage in the region of the
      initial lymphatics also led to a similar increase of lymph flow rates dependent
      on frequency as well as amplitude of skin displacement. Lymph flow rates during
      local skin massage reached a comparable order of magnitude regardless of whether
      the animal was alive or the heart had been arrested, suggesting that local lymph
      flow rates can be adjusted by periodic tissue motion independently of capillary
      fluid filtration pressures. The results indicate that periodic expansion and
      compression of initial lymphatics provide a mechanism for lymph pumping.

PMID- 8760174
TI  - Active renin and renin glycoform dynamics in the carotid artery.
AB  - Active renin and five major active renin glycoforms were measured in plasma and
      the carotid wall of anesthetized rabbits before and after 1.5- and 24-h bilateral
      nephrectomy (BNX). Before BNX, there was no difference in renin glycoform
      proportions between plasma and the carotid wall. Plasma renin concentration (PRC)
      fell by 67% after 1.5-h BNX due to preferential clearance of renin glycoforms
      I+II, but no significant change in renin concentration was seen in the carotid
      artery (or aorta). Twenty-four hours after BNX, PRC and carotid wall renin
      concentrations were reduced by 99.7 and 97.7%, respectively, while the proportion
      of renin glycoforms I+II in the carotid wall was significantly elevated. These
      data are consistent with the view that vascular renin is derived from plasma
      renin of renal origin. After BNX, renin disappearance from the carotid (and
      aortic wall) is slower than renin decay from plasma, and the less negatively
      charged active renin glycoforms I+II exit the carotid wall much more slowly than
      the more negatively charged glycoforms. After 24-h BNX, renin glycoforms I+II
      were still effluxing from the vascular wall and represented the only glycoforms
      present in the carotid wall.

PMID- 8760175
TI  - Mitochondrial dysfunction accompanies diastolic dysfunction in diabetic rat
      heart.
AB  - The objective of this study was to determine whether a defect in mitochondrial
      respiratory function accompanies the development of diabetic cardiomyopathy. The
      hypothesis tested in this study is that a decrease in Ca2+ uptake into
      mitochondria may prevent the stimulation of Ca(2+)-sensitive matrix
      dehydrogenases and the rate of ATP synthesis. Streptozotocin (55 mg/kg)-induced
      diabetic rats were used as a model of insulin-dependent diabetes mellitus. Hearts
      from 4-wk diabetic rats had basal heart rates and rates of contraction and
      relaxation similar to control. Isoproterenol caused a similar increase in the
      rate of contraction in diabetic and control hearts, whereas the peak rate of
      relaxation was reduced in diabetic hearts. Mitochondrial Ca2+ uptake was reduced
      in mitochondria from diabetic hearts after 2 wk of diabetes. Na(+)-induced Ca2+
      release was unchanged. State 3 respiration rate was depressed in mitochondria
      from diabetic rats only when the respiration was supported by the substrate of a
      Ca(2+)-regulated matrix enzyme. The pyruvate dehydrogenase activity was reduced
      in diabetic mitochondria compared with that of control. It was concluded that
      mitochondria from diabetic hearts had a decreased capacity to upregulate ATP
      synthesis via stimulation of Ca(2+)-sensitive matrix dehydrogenases. The
      impairment in the augmentation of ATP synthesis rate accompanies a decreased rate
      of relaxation during increased work load.

PMID- 8760176
TI  - Effects of oxygen on regional hemodynamics in hemorrhagic shock.
AB  - This study investigated mechanisms of the hemodynamic effects of oxygen in
      hemorrhagic shock induced by bleeding 30% of the total blood volume in
      anesthetized rats. An ultrasonic flowmeter was used to monitor regional blood
      flow. Changes in tissue perfusion were assessed by the laser-Doppler technique.
      The inhalation of 100% oxygen induced a significant increase in mean arterial
      blood pressure (MABP) and vascular resistance in the hindquarters, with a
      concomitant decrease in blood flow in the distal aorta and biceps femoris muscle.
      In contrast, oxygen did not change vascular resistance in the superior mesenteric
      artery (SMA) and renal beds and induced a significant increase in blood flow to
      the renal artery, SMA, and small bowel in hemorrhaged rats. L-Arginine (100 mg/kg
      iv) but not D-arginine or the vehicle (0.9% NaCl) completely abolished the
      effects of oxygen on blood pressure and reversed its effects on blood flow and
      resistance in the hindquarters and biceps femoris muscle. Administration of the
      nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (50 mg/kg
      iv) significantly increased MABP and the resistance in the three vascular beds.
      Pretreatment of hemorrhaged rats with a superoxide dismutase mimic, the NO-stable
      radical 2,2,6,6-tetramethylpiperidine-N-oxyl (5 mg/kg iv), resulted in
      significantly diminished effects of oxygen on hindquarter hemodynamics. These
      results demonstrate a differential effect of oxygen, which increases vascular
      resistance in the hindquarters without a significant effect in the splanchnic and
      renal beds, thus favoring an increase in splanchnic and renal perfusion. It is
      suggested that inactivation of NO by reactive oxygen species may underlie the
      effects of oxygen on hindquarter vascular tone during shock.

PMID- 8760177
TI  - Tissue specific expression of vascular smooth muscle angiotensin II receptor
      subtypes during ovine pregnancy.
AB  - Uteroplacentral responses to infused angiotensin II (ANG II) are less than those
      elicited by systemic vasculature. This does not reflect ANG II receptor (AT)
      downregulation but may reflect differences in AT-receptor subtypes expressed. We
      examined AT-receptor subtypes in smooth muscle (SM) from uterine (UA),
      mesenteric, renal, and mammary arteries and aorta from nulliparous (n = 12),
      pregnant (n = 18; 105-140 days, term = 145 days), postpartum (n = 5; 6-9 days
      after delivery), and nonpregnant parous (n = 14) ewes by assessing displacement
      of 125I-labeled ANG II binding by [Sar1, Ile8]ANG II (AT1 and AT2), losartan
      (AT1) PD-123319 (AT2), and CGP-42112A (AT2). AT2 receptors accounted for 75-90%
      of total binding in UA. Except for mammary arteries, other arteries expressed
      only AT1 receptors. Receptor subtype expression was not altered by reproductive
      state in any artery studied. With the use of autoradiography, AT2 receptors
      appear to predominate in media of small intramyometrial arteries, whereas AT1
      receptors predominate in the luminal portion. We therefore determined which
      subtype mediates endothelium-derived ANG II-induced increases in UA PGI2
      synthesis during pregnancy. ANG II (0.05 microM) increased PGI2 synthesis 62%,
      from 214 +/- 13 to 346 +/- 23 pg.mg-1.h-1 (P < 0.05). Losartan (1.0 microM)
      inhibited the rise in PGI2 (257 +/- 24 vs. 238 +/- 25 pg.mg-1.h-1), whereas 1.0
      microM PD-123319 had no effect (231 +/- 23 vs. 337 +/- 31 pg.mg-1.h-1; P < 0.05).
      AT2 receptors do not mediate ANG II-induced vasoconstriction, thus differences in
      uteroplacental and systemic sensitivity to ANG II may reflect predominance of AT2
      receptors in UASM and ANG II-induced increases in UA prostacyclin synthesis by
      endothelial AT1 receptors.

PMID- 8760178
TI  - Pulmonary vascular response to angiotensin II in canine pacing-induced heart
      failure.
AB  - The effects of angiotensin II(ANG II) on pulmonary vascular resistance and
      microvascular permeability were studied in isolated, blood-perfused, ventilated
      canine lung lobes from control animals (n = 40) and animals with pacing-induced
      heart failure (n = 15). Conditioned dogs were paced (245 beats/min) for 30.6 +/-
      0.9 (SE) days until left ventricular shortening fraction decreased by 56% (P <
      0.05). Baseline pulmonary arterial resistance (Ra) (19.1 +/- 1.6 vs. 8.0 +/- 1.1
      cmH2O.1(-1).min.100g) and venous resistance (Rv) (17.1 +/- 2.3 vs. 7.8 +/- 1.0
      cmH2O.1(-1).min.100 g) were greater (P < 0.05) in the paced group compared with
      controls, respectively. Increments in Ra (delta Ra) and Rv(delta Rv) were
      measured after intra-arterial boluses of ANG II (1-10 micrograms). ANG II
      produced a dose-dependent response in delta Ra that was enhanced after pacing (P
      < 0.05). There was no effect on delta Rv in either group. At increased venous
      pressure (Pv = 20 cmH2O), the increments in delta Ra were significantly
      attenuated in both groups. In control lobes at low Pv, delta Ra and delta Rv both
      tended to decrease with increased lobar blood flow, suggesting that blood flow
      affects the pulmonary vascular response of ANG II. The baseline capillary
      filtration coefficient (Kf,c) was not different in the paced group compared with
      control, nor was there any effect of ANG II on Kf,c in the paced group. However,
      Kf,c did increase after ANG II in the control groups evaluated at either low or
      high Pv (P < 0.05). This difference in Kf,c was not seen if the experiment was
      done at increased Pv but without ANG II administration. We conclude that the
      pulmonary vasoconstrictor activity of ANG II is modestly enhanced in canine
      pacing-induced heart failure. Nonetheless, ANG II does not likely contribute to
      increased pulmonary vascular resistance in vivo in heart failure, since this
      effect was abolished at increased Pv. Finally, the absence of any effect of ANG
      II on pulmonary microvascular permeability in the paced group is suggestive of
      some adaptive remodeling of the capillary endothelial barrier.

PMID- 8760179
TI  - Impaired Ca2+ handling is an early manifestation of pressure-overload hypertrophy
      in rat hearts.
AB  - Both cytosolic free Ca2+ ([Ca2+]i) decline and myocardial relaxation are slowed
      in severe hypertrophy and heart failure. However, it is not certain whether this
      occurs in mild to moderate hypertrophy. Therefore, we tested the hypotheses that
      slowing of [Ca2+]i decline 1) occurs in mild to moderate hypertrophy, 2) occurs
      in the absence of slowed relaxation, and 3) is related to the degree of
      hypertrophy. Experiments were performed on isolated rat hearts subjected to
      pressure overload. Indo 1 fluorescence was used as an index of [Ca2+]i. [Ca2+]i
      decline and myocardial relaxation were assessed by the time constant of
      exponential [Ca2+]i decline (tau Ca) and left ventricular (LV) pressure decline
      (tau p), respectively. Mean tau Ca was significantly increased in hearts from
      banded rats compared with sham-operated rats (59 +/- 13 vs. 45 +/- 5 ms, P =
      0.03). In contrast, there was no difference in mean tau p (28 +/- 3 vs. 29 +/- 5
      ms, P = not significant). There was a linear relationship between tau Ca and LV
      dry weight (r = 0.79). In summary, slowing of the [Ca2+]i transient decline
      occurred in mild to moderate hypertrophy. However, LV relaxation was unaffected.
      Furthermore, slowing of the [Ca2+]i transient decline was closely related to the
      degree of LV hypertrophy. These data suggest that slowing of [Ca2+]i decline is
      an early manifestation of pressure-overload hypertrophy that precedes slowing of
      relaxation.

PMID- 8760180
TI  - Myocardial adenosine A1 and A2 receptor activities during juvenile and adult
      stages of development.
AB  - Myocardial contractile responsiveness to beta-adrenoceptor stimulation is known
      to be reduced with maturation or aging. The present study was undertaken to
      determine the role of antiadrenergic A1 and stimulatory A2 adenosine receptors in
      the modulation of beta-adrenergic-elicited contractile performance of the heart
      at juvenile (approximately 25 days) and adult (approximately 79 days) stages of
      maturation. Isoproterenol, a beta-adrenergic agonist, at 10(-7) M produced a
      greater maximal increase in contractility, assessed as the maximal rate of left
      ventricular pressure development (+dP/dtmax), in immature than in mature hearts
      (104 and 80%, respectively), but produced a greater increase in venous adenosine
      concentration in the mature than in the immature hearts (738 and 277 nM,
      respectively). Isoproterenol at 10(-9) to 10(-8) M produced similar increases in
      contractility in the absence or presence of the A1 adenosine receptor antagonist
      xanthine amine congener (XAC; 0.5 microM) for both immature and mature hearts. In
      addition, XAC did not alter the isoproterenol-elicited contractile response in
      the immature heart during hypoperfusion induced by 50% reduction of coronary
      flow. However, in the mature heart, 10(-8) M isoproterenol elicited a
      significantly greater increase in +dP/dtmax during hypoperfusion in the presence
      (79%) vs. the absence (60%) of XAC. In both immature and mature hearts,
      hypoperfusion enhanced isoproterenol-elicited venous adenosine concentration by
      similar magnitudes of 76 and 72%, respectively. In further studies, the A2
      adenosine receptor antagonist 9-chloro-2-(2-furyl)[1,2,4]-triazolo[1,5
      c]quinazolin-5-amine (CGS-15943; 1 microM) reduced the isoproterenol-elicited
      contractile response of mature but not immature hearts during normal perfusion.
      These results suggest that myocardial adenosine modulates the beta-adrenergic
      elicited contractile response of the adult heart via activation of both A1 and A2
      adenosine receptors and that these functions of adenosine become expressed with
      myocardial maturation.

PMID- 8760181
TI  - Quantitative beat-to-beat analysis of heart rate dynamics during exercise.
AB  - Beat-to-beat heart rate (HR) dynamics were studied by plotting each R-R interval
      as a function of the previous R-R interval (Poincare plot) during incremental
      doses of atropine followed by exercise for 10 subjects and during exercise
      without autonomic blockade for 31 subjects. A quantitative two-dimensional vector
      analysis of a Poincare plot was used by measuring separately the standard
      deviation of instantaneous beat-to-beat R-R interval variability (SD1) and the
      standard deviation of continuous long-term R-R interval variability (SD2) as well
      as the SD1/SD2 ratio. Quantitative Poincare measures were compared with linear
      measures of HR variability (HRV) and with approximate entropy (ApEn) at rest and
      during exercise. A linear progressive reduction was observed in SD1 during
      atropine administration, and it remained almost at the zero level during exercise
      after a parasympathetic blockade. Atropine resulted in more variable changes in
      SD2 and the SD1/SD2 ratio, but during exercise after parasympathetic blockade, a
      progressive increase was observed in the SD1/SD2 ratio until the end of exercise.
      The SD1/SD2 ratio had no significant correlations with the frequency domain
      measures of HRV. However, the SD1/SD2 ratio had a modest correlation with ApEn at
      rest (r = -0.69, P < 0.001), but not during exercise (r = 0.27, P = NS). All
      measures of vagal modulation of HR decreased progressively until the ventilatory
      threshold level was reached, when sympathetic activation was reflected as changes
      in the SD1/SD2 ratio. These results show that quantitative two-dimensional vector
      analysis of a Poincare plot can provide useful information on vagal modulation of
      R-R interval dynamics during exercise that are not easily detected by linear
      summary measures of HRV or by ApEn.

PMID- 8760182
TI  - Decreased sensitivity to vasoconstrictors in aortic rings after acute exposure to
      nitric oxide.
AB  - Nitric oxide (NO) has been postulated as a regulator of vascular reactivity, and
      the current study tested the hypothesis that NO-induced decreased sensitivity to
      vasoconstrictors persists following removal of NO. Endothelium-denuded segments
      of rat aorta were incubated 2-4 h at 37 degrees C with the NO donor S-nitroso-N
      acetylpenicillamine (SNAP). Incubation produced rightward shifts in concentration
      response curves for phenylephrine [i.e., half-maximum effective concentration
      (EC50; in microM): control = 0.016, NO = 0.14], aluminum fluoride (i.e., EC50 in
      mM: control = 1.66, NO = 2.29), and KCl (i.e., EC50 in mM: control = 5.9, NO =
      23.9). Similar shifts were seen for two other NO donors. The SNAP-induced shift
      was not attenuated by a guanylyl cyclase inhibitor, LY-83583 (10 microM) and was
      not mimicked by 8-bromoguanosine 3',5'-cyclic monophosphate (100 microM). It was
      attenuated by 1,4-naphthoquinone (50 microM), an inhibitor of endogenous mono-ADP
      ribosyltransferases. NO incubation increased cGMP content (4.6 +/- 0.8 vs. 1.5 +/
      0.15 pmol/mg protein), an increase unaffected by 1,4-naphthoquinone (3.3 +/- 1.0
      pmol/mg protein) but prevented by LY-83583 (1.6 +/- 0.36 pmol/mg protein). ADP
      ribosylation of three proteins was observed in membranes from HEK 293 cells:
      88,66, and 38 kDa. ADP ribosylation of the 38-kDa protein was stimulated in a
      concentration-dependent manner by NO but was not decreased by 1,4-naphthoquinone.
      In conclusion, NO produces a long-lasting inhibition of vascular contractility by
      both a cGMP-dependent and -independent mechanism. Based on the observations of
      1,4-naphthoquinone, we conclude that the cGMP-independent mechanism is not
      stimulation of endogenous ADP ribosylation but some other covalent modification
      in the pathway that mediates contraction.

PMID- 8760183
TI  - Hypoxia does not directly stimulate ischemically sensitive abdominal visceral
      afferents during ischemia.
AB  - Abdominal ischemia activates ischemically sensitive sympathetic visceral
      afferents and evokes reflex excitation of the cardiovascular system. These
      afferents respond to ischemic metabolites, including lactic acid, bradykinin,
      prostaglandins, and reactive oxygen species. Severe hypoxemia also has been shown
      to activate these afferents. It is not known, however, if the regional tissue
      hypoxia induced by abdominal ischemia directly or indirectly activates
      ischemically sensitive visceral afferents. To determine the role of tissue
      hypoxia in activation of ischemically sensitive abdominal afferents, continuous
      single-unit activity of ischemically sensitive abdominal sympathetic C-fiber
      afferents (conduction velocity = 0.51-1.48 m/s) and regional tissue PO2, measured
      by a polarographic oxygen electrode in the porta hepatis, duodenum, or pancreas,
      were recorded simultaneously in anesthetized cats before and during 10-15 min of
      ischemia. Abdominal ischemia rapidly decreased regional tissue PO2 from 161 +/-
      10 to 8 +/- 2 mmHg (P < 0.01) within an interval of 136 +/- 12 s. By contrast,
      after longer latency (399 +/- 24 s, P < 0.01 vs. PO2 interval), the activity of
      these afferents increased from 0.06 +/- 0.01 to 0.33 +/- 0.07 imp/s (P < 0.01).
      Furthermore, the activity of ischemically sensitive afferents gradually increased
      throughout ischemia with peak activity (0.68 +/- 0.14 imp/s) occurring at 600 +/-
      39 s, although tissue PO2 remained constant. There was no correlation between the
      changes of tissue PO2 and discharge activity of these afferents (r = -0.428, P =
      0.144). These data suggest that tissue hypoxia induced by abdominal ischemia is
      not directly responsible for activation of ischemically sensitive sympathetic
      visceral afferents but likely acts in an indirect fashion by promoting formation
      of other metabolic products capable of activating these nerve endings.

PMID- 8760184
TI  - Myogenic responses of isolated rat skeletal muscle venules: modulation by
      norepinephrine and endothelium.
AB  - The pressure-induced myogenic response of large venules of skeletal muscle and
      its possible interactions with adrenergic receptor activation and endothelial
      factors have not yet been elucidated. Therefore, first-order venules of rat
      gracilis muscle were isolated, cannulated, and placed in an organ chamber.
      Changes in internal diameter of the vessels as a function of perfusion pressure
      (PP) were obtained. In response to increases in PP (0.5-17.5 mmHg), the diameter
      of venules increased from 197.1 +/- 23.96 to 369 +/- 14.1 microns. In passive
      conditions (in Ca(2+)-free solution), the pressure-diameter curve of venules
      shifted significantly upward. In the presence of norepinephrine (NE; 10(-6) M) in
      the bath solution, the pressure-diameter curve of active venules shifted
      significantly downward, and in the pressure-normalized diameter curve, a negative
      slope developed (-6.1 +/- 4.6). In both the absence and presence of NE, removal
      of endothelium significantly reduced venular diameters in the pressure ranges of
      3-5 and 2-5 mmHg, respectively, but did not change significantly the
      characteristics of the pressure-diameter curves. These findings indicate that the
      smooth muscle of venules actively responds to changes in intraluminal pressure.
      This response is greatly facilitated by NE and modulated by the endothelium. The
      myogenic response of skeletal muscle venules, especially in the presence of NE,
      could have a role in the regulation of the resistance and capacitance of venules
      and, consequently, blood flow and tissue exchange in skeletal muscle.

PMID- 8760185
TI  - Infusions of pressor agents selectively attenuate depressor responses to ACh in
      anesthetized dogs.
AB  - In dogs anesthetized with pentobarbital sodium (30 mg/kg iv), infusions of
      phenylephrine (PE; 1-3 micrograms.kg-1.min-1 iv for 30 min and longer) caused
      sustained elevations in blood pressure and suppressed depressor responses to
      acetylcholine (ACh; 1 microgram/kg iv) in a dose- and time-dependent manner. The
      dose-response curve for ACh (0.01-100 micrograms/kg iv)-induced depressor
      responses was shifted to the right by approximately 80-fold after an intravenous
      infusion of PE (3 micrograms.kg-1.min-1) for 120 min. Similar suppression was
      observed when infusions of methoxamine (5 micrograms.kg-1.min-1 iv),
      norepinephrine (3 micrograms.kg-1.min-1 iv under blockade of beta-adrenoceptors),
      or angiotensin II (0.3 micrograms.kg-1.min-1 iv) were carried out. However, in
      dogs treated with prazosin (1 mg/kg iv) or hydralazine (1 mg/kg iv) to prevent
      elevations in blood pressure over the baseline level, PE (3 micrograms.kg-1.min-1
      iv) failed to attenuate depressor responses to ACh. The suppression observed
      after PE infusion was specific to ACh-induced depressor responses; i.e., no
      suppression was observed on the depressor responses to other drugs, such as
      histamine, sodium nitroprusside, carbachol, and methacholine. Furthermore,
      neostigmine (bolus injection of 30 microgram/kg iv followed by an infusion of 15
      micrograms.kg-1.h-1 iv) greatly diminished the suppressive effect of PE. Except
      for a slight increase in acetylcholinesterase (AChE) activity in renal arterial
      segments, activities of both AChE and butyryl-cholinesterase in plasma,
      erythrocytes, and pulmonary and renal arterial segments were unchanged after PE
      infusion. These results suggest that prolonged elevation in blood pressure and/or
      vasoconstriction selectively attenuates depressor responses to ACh through
      accelerated degradation of this material.

PMID- 8760186
TI  - Encapsulation of VIP into liposomes restores vasorelaxation in hypertension in
      situ.
AB  - The purpose of this study was to determine whether vasoactive intestinal peptide
      (VIP) elicits vasodilation in the in situ peripheral microcirculation of hamsters
      with spontaneous hypertension and whether encapsulation of VIP into liposomes
      modulates this response. Using intravital microscopy, we found that suffusion of
      VIP (0.05 and 0.1 nmol) alone over cheek pouch resistance arterioles of
      normotensive hamsters elicited significant vasodilation that was potentiated and
      prolonged by encapsulation of the peptide into liposomes (P < 0.05). By contrast,
      VIP (0.5 and 0.1 nmol) had no significant effects on arteriolar diameter in
      hamsters with spontaneous hypertension. However, encapsulation of VIP into
      liposomes restored its vasorelaxant effects in hypertensive animals, although the
      duration of vasodilation was significantly shorter in comparison with controls (P
      < 0.05). Empty liposomes had no significant effects on arteriolar diameter in
      either group. These data indicate that VIP-induced vasodilation in the peripheral
      microcirculation in situ is impaired in essential hypertension and that
      encapsulation of VIP into liposomes restores, in part, this response.

PMID- 8760187
TI  - Bidirectional augmentation of heart rate regulation by autonomic nervous system
      in rabbits.
AB  - Although the characteristics of the static interaction between the sympathetic
      and parasympathetic nervous systems in regulating heart rate (HR) have been well
      established, how the dynamic interaction modulates the HR response remains
      unknown. We therefore investigated dynamic interaction by estimating the transfer
      function from nerve stimulation to HR using a band-limited Gaussian white-noise
      technique. The transfer function relating dynamic sympathetic stimulation to HR
      had characteristics of a second-order low-pass filter. Simultaneous tonic vagal
      stimulation at 5 and 10 Hz increased gain of the transfer function by 55.0 +/-
      40.1 and 80.7 +/- 50.5%, respectively (P < 0.05). The transfer function from
      dynamic vagal stimulation to HR had characteristics of a first-order low-pass
      filter. Simultaneous tonic sympathetic stimulation at 5 and 10 Hz increased the
      gain by 18.2 +/- 17.9 and 24.1 +/- 18.0%, respectively (P < 0.05). Thus
      interaction augmented dynamic gain bidirectionally, even though it affected mean
      HR antagonistically. By virtue of this interaction, the autonomic nervous system
      appears to extend its dynamic range of operation.

PMID- 8760188
TI  - Vanadate causes synthesis of endothelium-derived NO via pertussis toxin-sensitive
      G protein in pigs.
AB  - The effects of sodium orthovanadate, an inhibitor of protein tyrosine
      phosphatases, on the endothelial nitric oxide (NO) pathway were studied in vitro.
      Vanadate caused endothelium-dependent relaxations in isolated porcine coronary
      arteries, which were abolished by N omega-nitro-L-arginine methyl ester. The
      relaxations were also abolished by pertussis toxin, an inhibitor of certain G
      proteins. Tyrosine kinase inhibitors, genistein and alpha-cyano-3-ethoxy-4
      hydroxy-5-phenyl-methylcinnamamide (ST-638), significantly attenuated the
      vanadate-induced relaxations. Vanadate also caused pertussis toxin-sensitive,
      endothelium-dependent relaxations in isolated porcine renal and femoral arteries
      and jugular veins. Immunoblots, using an antibody to phosphotyrosines and to c
      Src in native porcine aortic endothelial cells, respectively, showed that
      vanadate induced an elevation of phosphotyrosine proteins and a decrease in the
      amount of the active form of c-Src family kinases; both changes were markedly
      suppressed by cotreatment with ST-638. These results indicate that in porcine
      blood vessels, vanadate causes a synthesis of endothelium-derived NO for which
      endothelial tyrosine kinases and pertussis toxin-sensitive G protein are
      considered to be closely involved.

PMID- 8760189
TI  - Diurnal heart rate variability in healthy subjects: effects of aging and sex
      difference.
AB  - To study the effects of aging and gender, circadian profiles of heart rate
      variability were evaluated for 105 healthy volunteers by frequency domain
      analysis of a Holter electrocardiogram record. The low-frequency (LF) component
      representing cardiac beta-adrenergic function showed high values for the 0800
      1200 period in male subjects and the 1200-2400 period in female subjects. The
      high-frequency (HF) component representing parasympathetic function showed a peak
      for the 0000-0600 period in both male and female subjects independent of age.
      Male subjects showed significantly higher %LF [LF/(LF + HF) x 100] than female
      subjects. LF showed consistently highly significant correlation with age. These
      basic findings can help elucidate the diurnal profile of cardiac nerve function
      and how it is affected by aging and sex difference.

PMID- 8760190
TI  - Differential effects of EMD-53998 on calcium-pressure relationship in normal and
      ischemic guinea pig heart.
AB  - We investigated the effects of EMD-53998 and digoxin on Ca2+ transients and left
      ventricular (LV) function in indo 1-loaded Langendorff guinea pig hearts. EMD
      53998 (10(-9) to 10(-5) M) and digoxin (10(-10) to 10(-6) M) increased +dP/dt and
      Ca2+ transients in normal hearts. The relative increase in Ca2+ transients by EMD
      53998 was similar to digoxin. At 10(-5) M, EMD-53998 increased LV end-diastolic
      pressure. Low-flow ischemia decreased +dP/dt by 50%, while indo 1 ratio increased
      by 10-25%. EMD-53998 (10(-9) to 10(-6) M) effectively restored the depressed
      +dP/dt with little effect on indo 1 ratio, but at 10(-5) M, it markedly elevated
      LV end-diastolic pressure and the beneficial effect on contractile dysfunction
      disappeared. Digoxin (10(-10) to 10(-7) M) failed to improve LV function, but at
      10(-6) M, it restored contractile dysfunction with a large increase in indo 1
      ratio. The relation between indo 1 ratio and +dP/dt clearly showed that EMD-53998
      restored contractile dysfunction by Ca2+ sensitization. These findings suggest
      that Ca2+ sensitization by EMD-53998 is an advantageous approach for ischemic
      contractile failure but impairs diastolic function.

PMID- 8760191
TI  - Stability of high-energy phosphates in right ventricle: myocardial energetics
      during right coronary hypotension.
AB  - This study was conducted to determine if mechanisms that reduce right coronary
      (RC) blood flow (RCBF) and right ventricular (RV) oxygen consumption (MVO2)
      during moderate RC hypotension preserve RV high-energy phosphates. RC arteries of
      anesthetized dogs were cannulated and perfused with arterial blood supplied by a
      pressurized extracorporeal circuit. RC perfusion pressure (RCPP) was either kept
      constant at 100 mmHg or reduced to 60 or 30 mmHg for 20 min followed by a freeze
      clamp biopsy of RV. Left ventricular (LV) biopsy was also performed to compare
      energy metabolism between RV and LV.RCBF and MVO2 significantly decreased when
      RCPP was reduced to 60 mmHg, but RV segment shortening (%SS) was unchanged; ATP,
      creating phosphate (CrP) and phosphorylation state of CrP ([CrP]/[Cr][Pi]) did
      not differ from control values. RV %SS, CrP, and phosphorylation state fell
      markedly at 30 mmHg RCPP. At 100 mmHg RCPP, CrP phosphorylation state in RV was
      only 35% of that in LV. These results indicate that RV increases its energetic
      efficiency without significant changes in high-energy phosphates or CrP
      phosphorylation state during moderate RC hypotension. Furthermore, the RV
      myocardium maintains a much lower energy level than LV myocardium, commensurate
      with its lower energy requirements.

PMID- 8760192
TI  - Proarrhythmic and antiarrhythmic actions of ion channel blockers on arrhythmias
      in the heart: model study.
AB  - We explain why 1) some class I and IV antiarrhythmia drugs could exert
      proarrhythmic action, 2) some class III drugs are effective in controlling
      reentrant arrhythmias, and 3) cycle length (CL) oscillation is involved in the
      termination or initiation of reentry. To explain these phenomena, we employ the
      following three means: bifurcation analysis, simulation, and model construction.
      Antiarrhythmia drugs are modeled by varying maximal conductances of Na+, Ca2+,
      and time-dependent delayed rectifying and time-independent inward rectifying K+
      channels in the Beeler-Reuter model, where the model cells are arranged in a
      ring. Bifurcation analysis predicts that there is a critical ring size (CRS) at
      which infinite ring behavior suddenly breaks down. Channel blockers can affect
      CRS in different manners: Na+ and Ca2+ blockers shorten CRS, whereas delayed
      rectifying K+ channel blockers and the inward K+ channel blockers lengthen CRS.
      This differential explains why some antiarrhythmia drugs are proarrhythmic (i.e.,
      shorten CRS) whereas others are antiarrhythmic (i.e., lengthen CRS). Simulation
      is then used to investigate how the drugs affect reentrant rhythms in the
      neighborhood of the CRS. We find that, in this region, CL, conduction velocity,
      and action potential duration become oscillatory. As ring size shrinks, the
      pattern of the oscillation becomes more complex. When the ring shrinks to a
      certain size, reentry can no longer be sustained, and it terminates after a few
      oscillatory cycles. To explain the basic mechanism involved in CL oscillation, we
      then construct a minimal model that contains a low-threshold fast inward current
      and a high-threshold slow inward current. With this model, we show that the two
      inward currents, with vastly different activation and inactivation kinetics,
      cause CL oscillations. Our results thus give theoretical explanations for the
      experimental finding of Frame's group in canine atrial tricuspid ring in vitro
      that class IC drugs can bring about stable reentry from nonsustained transient
      reentry, whereas class III drugs transform stable reentry to complex oscillations
      in CL. Our results also support the result of Frame's group, in that, in
      "adjustable" tricuspid rings, CL oscillation becomes more complex and its period
      becomes shorter as an excitable gap is shortened.

PMID- 8760193
TI  - Economy of contraction of cardiomyocytes as influenced by different positive
      inotropic interventions.
AB  - In the present study the effects of the novel cardiotonic agent EMD-57033 on
      contraction and energetic demand of isolated, electrically stimulated
      cardiomyocytes were investigated and compared with the effects of enhancement of
      extracellular calcium and of the beta-mimetic isoproterenol. In a specially
      designed setup [H. Rose, K.H. Strotmann, S. Popping, Y. Fischer, D. Kulsch, and
      H. Kammermeier. Am. J. Physiol. 261 (Heart Circ. Physiol. 30): H1329-H1334, 1991]
      parameters of contractile behavior and metabolic demand (O2 consumption) of
      isolated cardiac myocytes were measured. For a given enhancement of contractile
      performance (cell shortening) the increase in energetic demand (VO2) after
      application of EMD-57033 were markedly lower than on treatment with elevated
      extracellular Ca2+ concentration or with isoproterenol. This economization of
      positive inotropic effects was proposed to be due to two factors. First,
      stimulation-related ion cycling was only slightly enhanced with marked increase
      in contraction amplitude after application of EMD-57033. Second, calcium
      sensitization reflected in a leftward shift of the calcium concentration needed
      for half-maximum force development could be interpreted to be mediated by
      modulation of the cross-bridge dynamics of the myofilaments, where reduction of
      the switch-off rate of the cross bridges and prolongation of their force
      generating states were presumed to be involved. Lowered pH (7.0) decreased
      economy of contraction. EMD-57033 restored contraction amplitude and economy of
      contraction at lowered pH.

PMID- 8760194
TI  - Determination of PO2 and its heterogeneity in single capillaries.
AB  - We have applied the phosphorescence lifetime technique (Vanderkooi, J. M., G.
      Maniara, T. J. Green, and D. F. Wilson. J. Biol. Chem. 262: 5476-5482, 1987) to
      determine oxygen tension in single capillaries of the hamster retractor muscle.
      Palladium meso-tetra(4-carboxyphenyl)porphine (10 mg/ml, pH 7.40, bound to bovine
      serum albumin) was used as the phosphorescent oxygen sensor. Our measurement
      system consisted of a microscope configured for epi-illumination, a strobe flash
      lamp, a 430-nm bandpass excitation filter, and a 630-nm cut-on emission filter. A
      rectangular diaphragm was used to limit the illumination field to 10 microns x 10
      microns, and an end-window photomultiplier tube was used to detect the
      phosphorescence signal, which was then input to an analog-to-digital board in a
      personal computer. In vitro calibrations were carried out at 37 degrees C on
      samples flowing through a glass capillary tube (diameter, 300 microns) at four
      different O2 concentrations (0, 2.5, 5, and 7.5%). In vivo tests were carried out
      on arterioles, capillaries, and venules of the retractor muscle of anesthetized
      hamsters. The phosphorescent compound was administered by injection into a
      jugular vein (20 mg/kg). Phosphorescence decay curves were analyzed by a new
      model of heterogeneous oxygen distribution in the excitation/emission volume.
      Mean Po2 values and the local Po2 gradients within the excitation/ emission
      volume were calculated from phosphorescence life-times obtained from individual
      decay curves. The time course of Po2 obtained during 0.5-s measurement periods (5
      decay curves at 0.1-s intervals) at a given site along a capillary indicated the
      presence of a gradient in Po2 within the plasma space between and near red blood
      cells. Similar Po2 gradients were also detected in arterioles and venules. Mean
      Po2 values for arterioles, capillaries, and venules over the 0.5-s observation
      period were 27 +/- 5, 14 +/- 2, and 11 +/- 3 (SD) mmHg, respectively. The
      magnitude of the Po2 gradient in the arterioles, capillaries, and venules was 6
      +/- 1, 4 +/- 1, and 2 +/- 1 mmHg/micron, respectively.

PMID- 8760195
TI  - Hypertension, cardiac hypertrophy, and neurohumoral activity in a new animal
      model of obesity.
AB  - Although obesity is a major risk factor for morbidity and mortality, the
      mechanisms mediating cardiovascular abnormalities in response to weight gain are
      unclear. One reason for the paucity of information in this area is the lack of
      appropriate animal models for the study of human obesity. Therefore, the goal of
      the present study was to develop a small animal model of dietary-induced obesity
      that mimics many of the characteristics of human obesity. We studied female New
      Zealand White rabbits fed either a normal (n = 17) or high-fat diet (n = 15) and
      examined the cardiovascular consequences of obesity, including changes in blood
      pressure, humoral activation, and end-organ effects such as cardiac hypertrophy.
      After 12 wk, rabbits on the high-fat diet were 46% heavier than their lean
      counterparts (5.49 +/- 0.09 vs. 3.77 +/- 0.06 kg, respectively; P = 0.0001).
      Obese rabbits had higher resting heart rates than lean rabbits (220 +/- 7 vs. 177
      +/- 6 beats/min; P = 0.0001) and developed hypertension (96 +/- 2 vs. 85 +/- 1
      mmHg; P = 0.0001), hyperinsulinemia (32.5 +/- 3.4 vs. 15.5 +/- 1.0 microU/ml; P =
      0.0001), hyperglycemia (162.4 +/- 2.9 vs. 141.9 +/- 2.7 mg/dl; P = 0.0001), and
      elevated triglycerides (102.3 +/- 9.1 vs. 48.5 +/- 4.0 mg/dl; P = 0.0001). Obese
      rabbits also developed cardiac hypertrophy, as evidenced by left ventricular (LV)
      dry weights that were 52% greater in obese than in lean rabbits (P = 0.0003). In
      addition, LV total protein was increased in proportion to the increase in LV
      weight. The results of this study suggest that rabbits fed a high-fat diet for a
      period of 12 wk develop many of the characteristics of human obesity. The obese
      rabbit should provide a small and relatively inexpensive animal model to
      investigate mechanisms of obesity-related cardiovascular abnormalities.

PMID- 8760196
TI  - Muscarine-gated K+ channel: subunit stoichiometry and structural domains
      essential for G protein stimulation.
AB  - Coexpression in Xenopus oocytes of the cloned cardiac inward rectifier subunits
      Kir 3.1 and Kir 3.4 results in G protein-stimulated channel activity closely
      resembling the muscarinic channel underlying the inwardly rectifying K+ current
      in atrial myocytes. To determine the stoichiometry and relative subunit positions
      within the channel, Kir 3.1 and Kir 3.4 were coexpressed in varying ratios with
      cloned G beta 1 gamma 2 subunits and also as tandemly linked tetramers with
      different relative subunit positions. The results reveal that the most efficient
      channel comprises two subunits of each type in an alternating array within the
      tetramer. To localize regions important for subunit coassembly and G protein
      sensitivity, chimeric subunits containing domains from either Kir 3.1, Kir 3.4,
      or the G protein-insensitive subunit Kir 4.1 were expressed. The results
      demonstrate that the transmembrane domains dictate the potentiation of the
      coassembled channels and that, although the NH4- or COOH-termini of both subunits
      alone can confer G protein sensitivity, both termini are required for maximal
      stimulation by G beta 1 gamma 2.

PMID- 8760197
TI  - Acceptance of minerals and other compounds by calcium-deprived rats: 24-h tests.
AB  - We measured 24-h spontaneous intake of four to eight concentrations of 31
      different solutions by groups of rats fed control or low-calcium diets. Relative
      to controls, those fed low-calcium diet had increased acceptance of one or more
      concentrations of sodium chloride, sodium acetate, and sodium bicarbonate, but
      not sodium gluconate. Differences in palatability between these sodium salts were
      unimportant because the rats fed low-calcium diet consumed more sodium chloride
      even if this was made less acceptable by adulteration with citric acid. The
      possibility that calcium-deprived rats have an enhanced general cation or mineral
      appetite was supported by findings of increased acceptance of one or more
      concentrations of nine of ten chloride minerals tested (aluminum chloride,
      ammonium chloride, ferric chloride, ferrous chloride, magnesium chloride, sodium
      chloride, potassium chloride, strontium chloride, zinc chloride). However, there
      were no differences in acceptance of any concentration of cesium chloride,
      magnesium sulfate, or lead acetate. Moreover, calcium-deprived rats drank more
      hydrochloric acid and malic acid than did controls. Thus the effect of calcium
      deficiency on intake was not confined to minerals. Acidity or bitterness did not
      appear important because there was no difference between the groups in intake of
      sulfuric acid, citric acid, or quinine hydrochloride. Consistent with the
      exacerbating effects of phosphates on calcium deprivation, deprived rats had
      decreased intakes of phosphates (sodium phosphate, potassium phosphate). However,
      they also had decreased intakes of sucrose and saccharin. It is clear that
      calcium deprivation does not induce a general increase in acceptance of all taste
      solutions, but there appears to be no simple explanation for what these animals
      consume.

PMID- 8760198
TI  - Immediate acceptance of minerals and HCl by calcium-deprived rats: brief exposure
      tests.
AB  - We conducted two experiments to test the hypothesis that calcium consumption by
      calcium-deprived rats is unlearned and guided by oral cues. In experiment 1, we
      gave 23.5-h water-deprived control and calcium-deprived rats 30-min tests with
      water and various taste solutions. Relative to controls, calcium-deprived rats
      licked significantly less water and more 300 mM Ca.lactate in the first minute,
      more 50 mM HCl and 125 mM HCl in the first 10 min, and more 75 mM CaCl2, 150 mM
      CaCl2, and 300 mM CaCl2 by the end of the 30-min session. There was no difference
      between the groups at any time in lick rates for sodium solutions, quinine
      hydrochloride, sucrose octaacetate, or saccharin. In experiment 2, we gave 23-h
      water-deprived control, calcium-deprived, and sodium-deprived rats 10-min tests.
      During the first minute, calcium-deprived rats licked more than did control and
      sodium-deprived rats for 100 mM CaCl2, 100 mM FeCl2, and 20 mM Pb.acetate. Sodium
      deprived rats licked more than did control and calcium-deprived rats for 600 mM
      NaCl and less than did controls for 200 mM L-histidine. At the end of the 10-min
      session, sodium-deprived rats had higher lick rates for 100 mM FeCl2 than did
      control rats. There were no differences between the groups in lick rates for 1 mM
      quinine hydrochloride, 100 mM SrCl2, or 20 mM citric acid. The results suggest
      that calcium-deprived rats use innate oral factors to guide consumption of
      calcium and other solutions.

PMID- 8760199
TI  - Indispensable amino acid deficiency and increased seizure susceptibility in rats.
AB  - Repeated subthreshold stimulation of limbic brain areas increases seizure
      susceptibility in experimental models of epilepsy. In addition, acute dietary
      indispensable amino acid (IAA) deficiency activates the anterior piriform cortex
      (APC), a seizure-prone limbic brain area in the rat. Based on these two findings,
      we hypothesized that activation of the APC by chronic exposure to IAA-deficient
      diets might increase seizure susceptibility. Several nonessential amino acid
      neurotransmitters are important in seizures, but deficiencies of nontransmitter
      IAAs have not been well studied in seizure models. In four trials, we made
      injections of pentylenetetrazole intraperitoneally or of bicuculline into the APC
      in histidine-, isoleucine-, or threonine-deficient rats and controls. Increased
      susceptibility to seizures in the deficient animals was observed as increased
      severity of the seizures, decreased threshold for the dose of the chemostimulant
      and time to seizure, or a combination thereof. Pair-fed controls showed that this
      effect was not due to an energy deficit. This novel but robust finding suggests
      that IAA deficiency may increase vulnerability to seizures by repeated activation
      of the APC.

PMID- 8760200
TI  - Cortisol disposition and production rate in horses during rest and exercise.
AB  - The influence of a 56-km endurance exercise on cortisol kinetics and production
      rate was evaluated in six horses administered [3H]cortisol. Exercise resulted in
      an immediate two- to threefold increase in plasma cortisol, with values returning
      very rapidly to preexercise levels. During exercise, clearance and steady-state
      volume of distribution of total cortisol were greatly increased (338 +/- 95 vs.
      137 +/- 34 ml.kg-1.h-1 for clearance and 359 +/- 82 vs. 229 +/- 18 ml/kg for
      volume of distribution), whereas the terminal half-life decreased significantly
      (0.97 +/- 0.16 vs. 1.55 +/- 0.33 h). The estimated cortisol production rate was
      4.41 +/- 1.06 micrograms.kg-1.h-1 at rest and 26.75 +/- 5.11 micrograms.kg-1.h-1
      during exercise. We conclude that exercise triggers a large increase (x 6) in the
      adrenal secretion rate, which is not accurately reflected by the more limited
      increase (x 2-3) in plasma cortisol concentration, the actual measurement of
      plasma cortisol clearance being a prerequisite to assessment of adrenal gland
      function during exercise.

PMID- 8760201
TI  - Subcellular mechanisms of angiotensin II and arginine vasopressin activation of
      area postrema neurons.
AB  - Angiotensin II (ANG II) and arginine vasopressin (AVP) act on area postrema (AP)
      neurons to modulate the baroreflex. Because activation of AP neurons by either
      ANG II or AVP increases intracellular free Ca2+ concentrations ([Ca2+]i), the
      goal of this study was to analyze the factors affecting the [Ca2+]i responses to
      ANG II and AVP. Neurons were recovered from 14- to 16-day old rats and studied
      after 8-14 days in culture by use of the microscopic digital image analysis for
      fura 2-loaded cells. The effects of ANG II (100 nM) and AVP (100 nM) on [Ca2+]i
      were determined in normal (2 mM) and low (< 10 nM) extracellular Ca2+
      concentrations. In 143 of 240 neurons, ANG II increased [Ca2+]i 4.65-fold after
      20 s, and a similar response was observed in the absence of extracellular Ca2+
      (3.65-fold after 20 s). After 60 s of observation, steady-state levels of
      increased [Ca2+]i were still present under both conditions. Pretreatment with AT1
      antagonist or pertussis toxin abolished the response to ANG II. AVP also
      increased [Ca2+]i (3.6-fold at peak, 20 s) in normal and low extracellular Ca2+.
      Pretreatment with AVP V1 antagonist or pertussis toxin abolished the response to
      AVP. This study indicates that ANG II-induced increases in [Ca2+]i are
      independent of extracellular Ca2+ concentrations and involve the activation of
      AT1 receptors and a pertussis toxin-sensitive G protein. Although AVP affects a
      fewer number of AP neurons, the mechanisms of activation are also independent of
      extracellular Ca2+ concentration and are mediated by a pertussis toxin-sensitive
      G protein.

PMID- 8760202
TI  - High lipid content enhances the rate of oxygen diffusion through fish skeletal
      muscle.
AB  - The diffusion coefficient for O2 (Do2) and the solubility constant for O2 (alpha
      O2) were measured at 15 degrees C in oxidative muscle from striped bass (Morone
      saxatilis) that had been acclimated to 5 degrees and 25 degrees C. This design
      allowed us to test the hypothesis that changes in composition of the tissue that
      are known to occur during thermal acclimation may affect O2 movement. Our
      measurements permitted calculation of the diffusion constant for O2 (Ko2) through
      the tissue, which is a primary determinant of capacity for O2 flux. Under
      isothermal conditions, alpha O2 was 3.59 +/- 0.20 x 10(-2) and 6.64 +/- 0.27 x
      10(-2) ml O2.cm-3.atm-1 in tissues from 25 degrees- and 5 degrees C-acclimated
      animals, respectively. Because O2 is more soluble in lipid than aqueous phase,
      higher alpha O2 in tissues from cold-acclimated animals can be accounted for by
      the 13-fold increase in lipid content that is known to occur in oxidative muscle
      of striped bass during acclimation from 25 degrees to 5 degrees C. When measured
      under similar isothermal conditions, Do2 showed no significant difference between
      animals acclimated to warm or cold temperature; Do2 through tissues from 25
      degrees- and 5 degrees C-acclimated animals was 2.50 +/- 0.18 and 2.57 +/- 0.40
      cm2/s, respectively. Because alpha O2 increases, the calculated KO2 (DO2. alpha
      O2) is greater in tissue from cold- than from warm-acclimated fish. At
      physiological temperature, elevated lipid content in oxidative muscle of cold
      acclimated striped bass should result in enhanced intracellular movement of O2
      and at least partially offset the expected decrease in DO2 at cold temperature.

PMID- 8760203
TI  - Effects of the lipase inhibitor orlistat on intake and preference for dietary fat
      in rats.
AB  - Orlistat (Ols), a potent inhibitor of pancreatic lipase, was added to the fat
      source (1 or 4 mg Ols/g fat) of a macronutrient self-selection diet fed to adult
      female rats. The rats responded to the drug-induced reduction in fat absorption
      by decreasing their dietary fat intake and increasing their protein and
      carbohydrate intake in a dose-related manner. Total caloric intake also
      increased, but body weight gain was inhibited compared with the nondrug control
      group. When Ols was removed from the diet, nutrient selection, caloric intake,
      and body weight returned to control levels. In additional short-term experiments
      (30 min/day), rats developed a preference for a plain fat diet over an Ols-fat
      diet (4 mg/g fat) and also for a cue flavor paired with plain fat over a flavor
      paired with Ols-fat. Yet, when not given the choice, the rats consumed nearly as
      much Ols-fat as plain fat diet. These results indicate that, by reducing fat
      absorption, Ols reduced the attractiveness of dietary fat, although it did not
      make the fat diet aversive. In clinical use, lipase inhibitors may be effective
      in reducing dietary fat intake by reducing both the consumption and absorption of
      fat.

PMID- 8760204
TI  - Transplantation of lean fetal hypothalamus restores hypothalamic function in
      Zucker obese rats.
AB  - Rats with lesions to the ventromedial hypothalamus (VMH) manifest obesity,
      hyperphagia, and hyperinsulinemia, and fetal VMH transplantation into the third
      cerebroventricle of VMH-lesioned rats reduces the development of obesity caused
      by the lesion. The aim of this study was to determine whether the hyperphagia,
      hyperlipidemia, and hyperinsulinemia of obsese Zucker rats could be corrected by
      the transplantation of lean fetal Zucker hypothalamic tissue into the third
      cerebral ventricle of Zucker obese rats. After the fetal hypothalamic transplant
      (obese-HY), the rate of weight gain was significantly diminished compared with
      the unoperated Zucker obese rats and the obese rats that received the
      transplantation of a similar amount of frontal cortical tissue from the same
      fetus (obese-FC). Food intake was significantly lower, and plasma triacylglycerol
      and insulin concentrations were also significantly reduced in the obese-HY rats
      compared with the obese and obese-FC rats. The weight of the adrenal glands, the
      plasma adrenocorticotropic hormone concentration, the liver weight, and the liver
      lipid content in obese-HY were significantly less than those observed in the
      obese and obese-FC animals. There were no significant differences between the
      obese and the obese-FC animals or between unoperated Zucker lean rats and lean
      rats transplanted with lean fetal hypothalamus in all the parameters we
      determined in this study. Neovascularization and normal cellular morphology of
      the transplanted fetal hypothalamic tissue suggest that the transplanted neural
      and glial cells were viable and physiologically functional. In conclusion, this
      study offers evidence suggesting that the hypothalamic-pituitary-adrenal function
      is defective in Zucker obese rats, resulting in excessive weight gain,
      hyperphagia, hyperlipidemia, and hyperinsulinemia. The hypothalamic dysfunction
      in the Zucker obese rats is corrected by the transplantation of lean fetal
      hypothalamus.

PMID- 8760205
TI  - Effects of photoperiod and androgen on pituitary function and neuropeptide
      staining in Siberian hamsters.
AB  - Short photoperiods decrease gonadotropin secretion in Siberian hamsters, but it
      is unknown whether the negative feedback effects of androgens are amplified under
      such conditions, as is the case in other species. Photoperiod regulates the
      synthesis and secretion of gonadotropin-releasing hormone (GnRH), beta-endorphin,
      and arginine vasopressin (AVP), which influence gonadotropin release and sexual
      behavior but are themselves regulated by gonadal steroid hormones. To determine
      the role of androgen in these effects of daylength, immunostaining and
      gonadotropin concentrations were examined after 8 wk of exposure to long or short
      days (LD or SD). Animals were either left intact, castrated, or castrated with
      immediate or delayed replacement of testosterone (T). We also investigated
      effects of age on photoperiodic influences on brain peptides and serum hormone
      levels. Serum prolactin concentrations were regulated by photoperiod and by
      gonadal status in LD hamsters. Effects of T on follicle-stimulating hormone
      secretion were more pronounced in SD hamsters. Older hamsters were generally less
      responsive to effects of daylength on pituitary function. Photoperiod and gonadal
      status regulated the number of AVP-immunoreactive (ir) cells in the bed nucleus
      of the stria terminalis and the medial amygdala. Androgen treatment yielded more
      AVP-ir neurons in LD than in SD. Photoperiod influenced the number of GnRH-ir
      cells only in the medial septum of castrated hamsters. Daylength regulated beta
      endorphin-ir neurons in intact hamsters, but not in castrates. Only among old
      hamsters did photoperiod affect the influence of T on beta-endorphin staining in
      neurons and fibers. Such fiber staining was unaffected by photoperiod in intact
      and T-treated castrate hamsters, but was reduced in SD castrates. We conclude
      that daylength modulates the effects of androgen on gonadotropin secretion and
      influences the effect of T on neuropeptide staining in regionally specific
      patterns that depend on the age of the animal and its history of prior steroid
      exposure.

PMID- 8760206
TI  - Chemoreflex and endocrine components of cardiovascular responses to acute
      hypoxemia in the llama fetus.
AB  - We tested the hypothesis that the llama fetus has a blunted cardiovascular
      chemoreflex response to hypoxemia by investigating the effects of acute hypoxemia
      on perfusion pressure, heart rate, and the distribution of the combined
      ventricular output in 10 chronically instrumented fetal llamas at 0.6-0.7
      gestation. Four llama fetuses had the carotid sinus nerves sectioned. In the
      intact fetuses, there was a marked bradycardia, an increase in perfusion
      pressure, and a pronounced peripheral vasoconstriction during hypoxemia. These
      cardiovascular responses during hypoxemia in intact fetuses were accompanied by a
      pronounced increase in plasma vasopressin, but not in plasma angiotensin II
      concentrations. Carotid denervation prevented the bradycardia at the onset of
      hypoxemia, but it did not affect the intense vasoconstriction during hypoxemia.
      Plasma vasopressin and angiotensin II levels were not measured in carotid
      denervated fetuses. Our results do not support the hypothesis that the carotid
      chemoreflex during hypoxemia is blunted in the llama fetus. However, they
      emphasize that other mechanisms, such as increased vasopressin concentrations,
      operate to produce an intense vasoconstriction in hypoxemia. This intense
      vasoconstriction in the llama fetus during hypoxemia may reflect the influence of
      chronic exposure to the hypoxia of high altitude on the magnitude and gain of
      fetal cardiovascular responses to a superimposed acute episode of hypoxemia.

PMID- 8760207
TI  - Differentiated sympathetic neural control of the kidney.
AB  - Anatomic and neurophysiological methods were used to identify functionally
      specific subgroups of renal sympathetic nerve fibers. The distribution of
      diameters of the predominating unmyelinated fibers showed a major mode at 1.1
      microns and a minor mode at 1.6 microns. The conduction velocity was 2.10 +/-
      0.10 m/s, consistent with unmyelinated C fibers. Analysis of strength-duration
      relationships during renal nerve stimulation showed that both rheobase and
      chronaxie values for renal blood flow were greater than those for urinary flow
      rate and were independent of stimulation frequency. This difference suggests a
      higher stimulation threshold (smaller diameter) for those renal nerve fibers
      involved in the renal blood flow response (renal vasoconstriction) compared with
      those for the urinary flow rate response (antidiuresis) to renal nerve
      stimulation. Single renal units that responded to preganglionic splanchnic nerve
      stimulation were studied. Those with spontaneous activity (88%) responded to
      stimulation of arterial baroreceptors, arterial and central chemoreceptors, and
      peripheral thermoreceptors, whereas those that lacked spontaneous activity (12%)
      responded only to stimulation of peripheral thermoreceptors (known to produce
      renal vasoconstriction). A minority population of single renal units has been
      identified that, although renal vasoconstrictor, does not exhibit other
      characteristic features of vasoconstrictor neurons (i.e., responsiveness to
      stimulation of arterial baroreceptors and arterial and central chemoreceptors).
      These findings suggest the existence of functionally specific subgroups of renal
      nerve fibers.

PMID- 8760208
TI  - Respiration and medullary blood flow during sinusoidal hypoxia in the
      peripherally chemodenervated cat.
AB  - The hypothesis that hypoxic respiratory depression is mediated by changes in
      medullary blood flow (MBF) was assessed in 18 anesthetized, paralyzed,
      vagotomized, peripherally chemodenervated, ventilated cats exposed to sinusoidal
      hypoxic hypoxia. In nine cats, the dynamic response of the central respiratory
      controller to hypoxia was studied by varying the cycle time of sinusoidal hypoxia
      (cycle time = 2.5, 4, 6, 10, and 15 min). Peak phrenic neurogram amplitude (PNA)
      followed sinusoidal oscillations in the hypoxic input [arterial O2 saturation
      (SaO2)] at all cycle times. The relationship between PNA and SaO2 was expressed
      as the transfer function of the system and was approximated as a first-order
      differential equation with a time constant of 78 +/- 1 s, a value consistent with
      a previous measurement of the time constant of the change in respiration
      following a change in brain blood flow. In a separate study, MBF was continuously
      measured during sinusoidal hypoxia (cycle time = 6 min; n = 9) with a laser
      Doppler flow probe to directly assess the role of MBF in production of hypoxic
      respiratory depression. PNA and MBF followed SaO2 oscillations during sinusoidal
      hypoxia. Infusion of sodium nitroprusside (20 micrograms.kg-1.min-1 iv) increased
      MBF by 30-40% and abolished MBF oscillations during subsequent sinusoidal hypoxia
      but had no effect on PNA oscillations. We conclude that the increase in brain
      blood flow seen during sinusoidal hypoxia is not the primary cause of the
      accompanying central hypoxic respiratory depression.

PMID- 8760209
TI  - An interleukin-1 receptor fragment inhibits spontaneous sleep and muramyl
      dipeptide-induced sleep in rabbits.
AB  - Interleukin-1 (IL-1) is hypothesized to be involved in physiological sleep
      regulation and in sleep responses occurring during infectious disease. If this
      hypothesis is correct, then inhibition of endogenous IL-1 should reduce both
      normal sleep and N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP)-induced sleep. MDP
      is a somnogenic substance derived from bacterial cell walls. We report here the
      effects of a synthetic IL-1 receptor fragment corresponding to amino acid
      residues 86-95 of the human type I IL-1 receptor (IL-1RF) on spontaneous sleep
      and IL-1 beta- and MDP-induced sleep and fever in rabbits. Two doses of the IL
      1RF (25 and 50 micrograms) were injected into normal rabbits
      intracerebroventricularly (icv). Both doses significantly decreased spontaneous
      non-rapid eye movement sleep (NREMS) across a 22-h recording period. Pretreatment
      of rabbits with 25 micrograms of IL-1RF blocked the somnogenic actions of 10 ng
      icv IL-1. Similarly, central pretreatment of animals with 25 micrograms IL-1RF
      significantly attenuated the NREMS-promoting and REMS-suppressive actions of 150
      pmol MDP injected centrally. The increase in NREMS and decrease in REMS induced
      by systemic injection of 12.5 micrograms/kg MDP were also significantly
      suppressed by central administration of 50 micrograms IL-1RF. In contrast, the
      febrile response induced by either intracerebroventricularly or intravenously
      injected MDP were not significantly affected by IL-1RF. These results support the
      hypothesis that endogenous, brain-derived IL-1 contributes to the maintenance of
      normal sleep and may mediate sleep responses to systemic as well as central
      bacterial infections.

PMID- 8760210
TI  - Blood pressure and fluid-electrolyte balance in mice with reduced or absent ANP.
AB  - Atrial natriuretic peptide (ANP)-gene knockout mice of three genotypes (+/+, +/-,
      and -/-) were maintained on a low-salt diet (0.008% NaCl). They were then fed
      either the same low-salt diet or a high-salt diet (8% NaCl) for 1 wk. No
      differences were found among genotypes in daily food and water intakes or in
      urinary volume and electrolyte excretions. Arterial blood pressures measured in
      anesthetized animals at the end of the dietary regimen were significantly and
      similarly increased in -/- compared with +/+ mice on each diet. Renal excretion
      of fluid and electrolytes was measured in anesthetized mice before and after
      acute blood volume expansion. No genotype differences were observed before volume
      expansion. After volume expansion the wild-type (+/+) mice had much greater
      saluretic responses than either the heterozygous (+/-) or the homozygous mutant (
      /-) animals on the low-salt diet but not on the high-salt diet. We conclude that
      ANP lowers blood pressure in the absence of detected changes in renal function;
      ANP is not essential for normal salt balance, even on high-salt intake; and ANP
      is essential for the natriuretic response to acute blood volume expansion on a
      low-salt but not high-salt intake.

PMID- 8760211
TI  - Identification and characterization of zeta-opioid receptor in human colon
      cancer.
AB  - Opioid growth factor (OGF, [Met5]enkephalin) inhibits the growth of human colon
      cancer in nude mice in a receptor-mediated fashion. Ligand binding assays using
      HT-29 human colon cancer tissue and [3H][Met5]enkephalin were performed to
      characterize the receptor responsible for the growth-regulatory effects of OGF in
      colon cancer. Specific and saturable binding was detected, and Scatchard analysis
      revealed that the data were consistent for a single binding site with a binding
      affinity of 15.4 +/- 2.0 nM and a binding capacity of 364.8 +/- 25.7 fmol/mg
      protein. Subcellular fractionation studies revealed that binding was restricted
      to the nuclear fraction. Competition experiments showed that cold
      [Met5]enkephalin was the most effective ligand at displacing
      [3H][Met5]enkephalin. Binding to radiolabeled [Met5]enkephalin also was detected
      in colon cancers obtained from surgical resections. The function, pharmacological
      and biochemical characteristics, distribution, and subcellular location of this
      OGF receptor in human colon cancer are consistent with the zeta-opioid receptor.

PMID- 8760212
TI  - Regulation of DNA synthesis of myocardial and epicardial cells in developing rat
      heart by [Met5]enkephalin.
AB  - Endogenous opioids serve as negative growth factors in neural and nonneural
      tissues in addition to being neuromodulators. This study investigated the
      hypothesis that native opioid peptides are inhibitory growth factors in heart
      development. DNA synthesis of ventricular myocardial and epicardial cells in 1
      day-old rats was examined. Administration of a variety of opioids and peptides
      revealed that [Met5]enkephalin had the greatest inhibitory effect on DNA
      synthesis; peptides related to mu-, delta-, kappa-, epsilon-, and sigma-receptors
      had no influence on cell proliferation, even at concentrations as high as 10
      mg/kg. [Met5]enkephalin, also termed opioid growth factor (OGF), depressed DNA
      synthesis at 1 and 10 mg/kg but not at 0.01 or 0.1 mg/kg. The effects of OGF were
      noted within 1 h of treatment, persisted for as long as 22 h after drug
      administration, and could depress DNA synthesis in myocardial and epicardial
      cells to 43 and 36%, respectively, of control values. The effect of OGF on DNA
      synthesis of heart cells was opioid receptor-mediated. Organ culture experiments
      revealed that opioids acted directly on developing cardiac cells. Both OGF and
      its receptor, zeta, were detected in heart cells of 1-day-old rats by
      immunocytochemistry. mRNA for preproenkephalin, the precursor to OGF, was
      observed in 1-day-old rat heart. These results indicate that an autocrine- or
      paracrine-produced endogenous opioid peptide (i.e., OGF) and its receptor (i.e.,
      zeta) are present in the developing heart and govern DNA synthesis, with OGF
      acting directly as a tonic negative regulator of cell generation.

PMID- 8760213
TI  - Inhibition of stimulated and basal ACTH by cortisol during ovine pregnancy.
AB  - In pregnant ewes, as in pregnant women, plasma adrenocorticotropic hormone (ACTH)
      and cortisol concentrations are increased. Inhibition of free cortisol
      concentrations by dexamethasone, a synthetic glucocorticoid, is reduced in
      pregnant women compared with nonpregnant women. These experiments were designed
      to test the hypothesis that basal and stimulated ACTH concentrations are less
      sensitive to negative feedback inhibition by cortisol in pregnant ewes than in
      nonpregnant ewes. Ewes were infused with vehicle and with cortisol at two
      different rates (1 and 2 micrograms.kg-1.min-1) for 1 h; plasma ACTH
      concentrations during and after the infusion and after subsequent stimulation by
      hypotension were measured. Basal plasma ACTH concentrations during a 2-h infusion
      of cortisol (2 micrograms.kg-1.min-1) were also measured in undisturbed ewes.
      Cortisol significantly inhibited both stimulated and basal ACTH. The degree of
      suppression of ACTH was not reduced in the pregnant ewes compared with the
      nonpregnant ewes. The results indicate that both basal and stimulated ACTH are
      sensitive to negative feedback inhibition by cortisol during ovine pregnancy.

PMID- 8760214
TI  - Characterization of cholecystokinin binding sites in goldfish brain and
      pituitary.
AB  - The characterization and distribution of cholecystokinin (CCK)/gastrin binding
      sites were determined in the goldfish central nervous system (CNS). Binding of
      125I-sulfated CCK octapeptide (125I-CCK-8s) in tissue sections was found to be
      saturable, reversible, time dependent, and displaceable by CCK/gastrin-like
      peptides. Analysis of saturable equilibrium binding revealed a high-affinity
      binding site (dissociation constant of 0.706 +/- 0.188 nM), which also displayed
      high affinity for gastrin-17s and caerulein. Lower affinities were observed for
      the nonsulfated forms of CCK-8 and gastrin-17. These findings suggest that a
      single primitive CCK/gastrin receptor exists in the goldfish CNS. The
      distribution of CCK/gastrin binding sites in the goldfish brain and pituitary
      revealed high densities within the telencephalon and preoptic hypothalamus, as
      well as within hypothalamic nuclei associated with the brain feeding center. High
      densities of binding sites were also localized within the midbrain tegmentum and
      optic tectum of the midbrain, the facial lobe and vagal lobe of the hindbrain,
      and within the pituitary pars distalis. Overall, these findings support previous
      studies that indicate that CCK/gastrin-like peptides play a role in the central
      regulation of feeding behavior and pituitary hormone secretion in fish.

PMID- 8760215
TI  - Fatty acid oxidation modulates the eating response to the fructose analogue 2,5
      anhydro-D-mannitol.
AB  - The fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) stimulates feeding behavior
      in rats apparently through its effects on hepatic energy metabolism, where it
      reduces glucose utilization, traps phosphate, and decreases ATP. The extent to
      which the magnitude and duration of the eating response are dependent on the
      ability of the liver to switch to fat oxidation for energy production was
      investigated by manipulating substrate availability through dietary and
      pharmacological means. Rats adapted to a high-fat, low-carbohydrate diet
      preferentially use fat fuels for hepatic energy production and were insensitive
      to the effects of 2,5-AM on food intake. The lack of an eating response occurred
      despite similar changes in plasma fuels and liver glycogen compared with rats fed
      a low-fat, high-carbohydrate diet. In contrast, inhibiting fatty acid oxidation
      with methyl palmoxirate, which blocks transport of long-chain fatty acids to the
      mitochondria, potentiated the ability of 2,5-AM to stimulate feeding without
      altering its effects on plasma and liver fuels. These data demonstrate that the
      eating response to 2,5-AM is modulated by the availability of fat fuels and
      implicate a mechanism for initiation of feeding that is not dependent on
      inhibition of carbohydrate metabolism per se but rather integrates information
      about the use of both types of fuels.

PMID- 8760217
TI  - Structure and concentrating ability of the mammalian kidney: correlations with
      habitat.
AB  - Mammals with relatively long loops of Henle for their body size tend to have
      greater than average urinary concentrating ability, but the relationship between
      urine osmolality (Uosm) and absolute length of the loop of Henle (generally
      estimated as medullary thickness) is neither proportional nor direct. Uosm is
      independent of the thickness of the outer medulla (corresponding to the length of
      the medullary thick ascending limb), which scales similarly with body mass in
      animals from mesic, arid, and freshwater environments. After adjustment for the
      effect of body size, there is a significant relationship between the thickness of
      the inner medulla (corresponding to length of the thin ascending limb) and
      concentrating ability, but only in species from mesic environments; for these,
      the thickness of the inner medulla accounts for only 16% of the interspecific
      variability in Uosm. In marine mammals, both the cortex and medulla are
      surprisingly thin, yet these animals produce very concentrated urine for their
      size. A functional dependence of urinary concentrating ability on the length of
      the loop of Henle is a central tenet of countercurrent multiplier theory, but the
      correlation of maximum urine concentration with loop length is weak at best and
      largely reflects the influence of the thin ascending limb.

PMID- 8760216
TI  - Microglia digest Staphylococcus aureus into low molecular weight biologically
      active compounds.
AB  - Excess sleep and fever are central nervous system (CNS) facets of the acute phase
      response; these responses are induced by microbial products, such as muramyl
      peptides, via their ability to enhance cytokine production. Although peripheral
      macrophages are known to digest bacteria, thereby releasing muramyl peptides
      that, in turn, stimulate cytokine production, it was unknown whether CNS
      phagocytes such as microglia also had this capacity. Primary cultures of
      microglia were allowed to phagocytize and digest Staphylococcus aureus
      radiolabeled with a cell wall-specific marker. Radiolabeled low molecular weight
      substances released into the culture medium were partially purified and tested
      for the ability to induce excess sleep, fever, and cytokine production. These
      substances increased non-rapid eye movement sleep, electroencephalographic slow
      wave activity, and brain temperature after intracerebroventricular injection into
      rabbits. They also induced interleukin-1, tumor necrosis factor, and the
      interleukin-1 receptor antagonist production in human monocytes. Results suggest
      that microglia perform fundamental macrophage functions and further implicate
      microglia as resident immunocompetent cells.

PMID- 8760218
TI  - Hindbrain GRP receptor blockade antagonizes feeding suppression by peripherally
      administered GRP.
AB  - Bombesin (BN)-like peptides injected peripherally or centrally suppress food
      intake in rats. The relationship between the central and peripheral actions of BN
      is unknown. However, experimental evidence supports a critical role for the
      caudal hindbrain in mediating the feeding effects of BN. To investigate this
      relationship further, we examined the ability of fourth ventricular infusion of a
      specific gastrin-releasing peptide (GRP) antagonist, [D-F5, Phe6, D-Ala11]BN-(6
      13) methyl ester (BN-ME), to block suppression of glucose intake (0.5 kcal/ml)
      produced by intraperitoneal administration of GRP-(18-27) in 5-h food-deprived
      male Sprague-Dawley rats (n = 10). We found that fourth ventricular
      administration of 10, 32, and 100 ng BN-ME blocked the suppression of glucose
      intake produced by peripherally administered 10 nmol/kg GRP-(18-27). The most
      effective dose of BN-ME (100 ng) blocked the ability of peripheral injection of
      GRP-(18-27) to inhibit glucose intake but had no effect on intake when given
      alone. These results demonstrate that the availability of caudal hindbrain GRP
      receptors is necessary for peripherally administered GRP-(18-27) to reduce food
      intake in rats.

PMID- 8760219
TI  - Ciliary neurotrophic factor is catabolic and shares with IL-6 the capacity to
      induce an acute phase response.
AB  - Ciliary neurotrophic factor (CNTF), a member of the interleukin-6 (IL-6)
      superfamily, has recently been shown to induce several inflammatory responses
      when administered to healthy animals, including induction of fever and a hepatic
      acute phase protein response. In the present report, 250 micrograms.kg body wt
      1.day-1 of recombinant rat CNTF or murine IL-6 were repeatedly administered to
      healthy mice over a 7-day period in an effort to compare biological responses. In
      addition to its in vivo capacity to elicit a hepatic acute phase response,
      administration of CNTF, but not IL-6, produced profound anorexia and lean tissue
      wasting in mice. In C57B1/6 mice, 7 days of CNTF administration led to a 21% loss
      in carcass protein content, resulting from carcass protein breakdown rates being
      increased 218% over freely fed controls (both P < 0.01). Protein synthesis rates
      in carcass protein were also increased in CNTF-treated mice compared with both
      freely fed animals and mice pair-fed equivalent quantities of food. In contrast,
      administration of equivalent quantities of murine IL-6 had no effect on food
      intake or body weight in mice, although IL-6 produced a similar hepatic acute
      phase response, as determined by increases in serum amyloid P and seromucoid
      fraction and increases in total hepatic protein synthesis. However, when CNTF was
      coincubated with extensor digitorum longus muscles from juvenile rats in vitro,
      rates of total muscle and myofibrillar protein degradation and muscle protein
      synthesis were unchanged. We conclude that CNTF can regulate in vivo both
      skeletal muscle remodeling as well as the distant anorexia and hepatic acute
      phase protein responses. In the case of skeletal muscle, these actions are both
      indirect and independent of the associated anorexia. These properties of CNTF are
      distinct from IL-6, which when administered to the mouse at these doses is
      neither anorexigenic nor cachexia producing.

PMID- 8760220
TI  - Regulation of glucose turnover and hormonal responses during electrical cycling
      in tetraplegic humans.
AB  - To examine the importance of blood-borne vs. neural mechanisms for hormonal
      responses and substrate mobilization during exercise, six spinal cord-injured
      tetraplegic (C5-T1) males (mean age: 35 yr, range: 24-55 yr) were recruited to
      perform involuntary, electrically induced cycling [functional electrical
      stimulation (FES)] to fatigue for 24.6 +/- 2.3 min (mean and SE), and heart rate
      rose from 67 +/- 7 (rest) to 107 +/- 5 (exercise) beats/min. Voluntary arm
      cranking in tetraplegics (ARM) and voluntary leg cycling in six matched, long
      term immobilized (2-12 mo) males (Vol) served as control experiments. In FES,
      peripheral glucose uptake increased [12.4 +/- 1.1 (rest) to 19.5 +/- 4.3
      (exercise) mumol.min-1.kg-1; P < 0.05], whereas hepatic glucose production did
      not change from basal values [12.4 +/- 1.4 (rest) vs. 13.0 +/- 3.4 (exercise)
      mumol.min-1.kg-1]. Accordingly, plasma glucose decreased [from 5.4 +/- 0.3 (rest)
      to 4.7 +/- 0.3 (exercise) mmol/l; P < 0.05]. Plasma glucose did not change in
      response to ARM or Vol. Plasma free fatty acids and beta-hydroxybutyrate
      decreased only in FES experiments (P < 0.05). During FES, increases in growth
      hormone (GH) and epinephrine and decreases in insulin concentrations were
      abolished. Although subnormal throughout the exercise period, norepinephrine
      concentrations increased during FES, and responses of heart rate,
      adrenocorticotropic hormone, beta-endorphin, renin, lactate, and potassium were
      marked. In conclusion, during exercise, activity in motor centers and afferent
      muscle nerves is important for normal responses of GH, catecholamines, insulin,
      glucose production, and lipolysis. Humoral feedback and spinal or simple
      autonomic nervous reflex mechanisms are not sufficient. However, such mechanisms
      are involved in redundant control of heart rate and neuroendocrine activity in
      exercise.

PMID- 8760221
TI  - Acute and chronic angiotensin hypertension: neural and nonneural components, time
      course, and dose dependency.
AB  - We examined the mechanisms mediating hypertension in conscious rats during acute
      and chronic infusion of angiotensin II (ANG II) at pressor doses (50, 100, and
      200 ng.kg-1.min-1). Trimethaphan-induced blood pressure reduction was inversely
      related to the acute dose of ANG II, consistent with a constrictor action of ANG
      II on vascular smooth muscle and withdrawal of sympathetic tone. During chronic
      ANG II infusion, the entire increase in mean arterial pressure (MAP) was
      inhibited by trimethaphan, consistent with neural mediation. During acute ANG II
      hypertension, the AT1-specific receptor blocker losartan induced a large fall in
      MAP (64 +/- 4 mmHg) in ganglion-blocked (chlorisondamine) rats, whereas, during
      chronic ANG II hypertension, losartan had only a small hypotensive effect (11 +/-
      3 mmHg). To determine the time course of the change from vascular smooth muscle
      action to neural action, we measured MAP in response to trimethaphan during the
      first 24 h of ANG II infusion. After 5 h, the minimal MAP in response to
      trimethaphan was significantly higher than that before ANG II. After 10 h of
      infusion, trimethaphan decreased MAP to pre-ANG II levels. That is, the neural
      component was fully active after only 10 h of infusion in rats. Finally, chronic
      administration of ANG II resulted in a dose-related increase in MAP that, at all
      doses, was completely inhibited by trimethaphan. These findings are consistent
      with ANG II acting primarily on vascular smooth muscle during acute infusion and
      via neural pathways during chronic treatment. The transition from direct smooth
      muscle to indirect neural action is rapid in rats (< 10 h), and the MAP and
      neural responses to ANG II are dose related during chronic hypertension.

PMID- 8760222
TI  - Differences in calcium kinetics between adolescent girls and young women.
AB  - Rapid bone accretion occurs throughout childhood but peaks during adolescence.
      The achievement of optimal peak bone mass, which can protect against osteoporosis
      later in life, is greatly dependent on rates of bone accretion. To identify
      differences in calcium metabolism during rapid vs. slower bone accretion, calcium
      kinetics were compared in 14 healthy girls aged 11-14 yr and 11 women aged 19-31
      yr. Calcium kinetics were measured while subjects were undergoing a calcium
      balance study in a camp simulating a free-living environment. After 7 days on a
      diet containing 1,330 mg Ca/day, two stable isotopes were administered (44Ca
      orally and 42Ca intravenously), and blood samples and all urine and feces were
      collected for 14 days. Samples were analyzed for total calcium by atomic
      absorption spectrophotometry and for enrichment of 42Ca and 44Ca by fast atom
      bombardment mass spectrometry. Data from serum, urine, and feces were analyzed
      using the Simulation, Analysis and Modeling (SAAM) software. Data were fitted by
      a three-compartment model; the first pool was the same size in girls and women
      (1.6 g) but the second and third pools were larger in girls (2.85 vs. 1.66 g and
      12 vs. 5 g). Compared with the women, girls absorbed more calcium from the diet
      (38 vs. 22% or 494 vs. 283 mg/day), excreted less calcium in urine (100 vs. 203
      mg/day), deposited more calcium in bone (1,459 vs. 501 mg/day), and resorbed more
      calcium from the skeleton (1,177 vs. 542 mg/day), whereas endogenous calcium
      excretion did not differ between girls and women (112 vs. 121 mg/day). Girls
      retained more calcium than women (282 vs. -41 mg/day) through increased
      absorption, lower urine excretion, and higher bone turnover.

PMID- 8760223
TI  - Potency of naloxone's anorectic effect in rats is dependent on diet preference.
AB  - Modulation of feeding behavior by neuropeptide Y (NPY) and opioids is well
      established, but the possibility that these neural influences provoke specific
      appetites, NPY for carbohydrate and opioids for fat, has also been considered. In
      other studies, intake of standard chow after NPY stimulation can be blocked by
      naloxone, indicating an interaction between these systems in the regulation of
      feeding. The present experiments examined the nature of NPY-opioid interactions
      in diet selection. Rats were administered NPY and naloxone concurrently, then
      chose between high-fat and high-carbohydrate diets. Subcutaneous administration
      of naloxone (0.01-0.3 mg/kg) potently reduced intake of the preferred diet, but
      not the nonpreferred diet. A similar pattern of selection was seen in a separate
      experiment where the same doses of naloxone were administered after 24-h food
      deprivation. These data support the idea that the opioid system mediates the
      "rewarding" aspects of feeding.

PMID- 8760225
TI  - Effect of vagal and splanchnic nerve section on Fos expression in ferret brain
      stem after emetic stimuli.
AB  - Previous studies have demonstrated that intraduodenal hypertonic saline (IHS)
      induces dense Fos expression within two regions of the ferret dorsal vagal
      complex (DVC): the area postrema (AP) and the medial subnucleus of the nucleus of
      the solitary tract (mn). The aims of the present experiments were to determine
      the peripheral pathways involved in excitation of DVC neurons after IHS and the
      relative importance of mn and AP excitation in the emetic response to this
      stimulus. The emetic response and the distribution of Fos were examined after IHS
      in animals that had received either vagotomy alone, vagotomy and splanchnic nerve
      section, or sham operation. The emetic response was studied in both awake and
      anesthetized animals, and Fos induction was studied in anesthetized animals.
      Vagotomy alone or combined with splanchnic nerve section abolished the emetic
      response and the area of dense labeling within the mn and reduced but did not
      abolish the labeling in the AP. It was concluded that both the emetic reflex and
      the dense expression of Fos within the mn after IHS are dependent on an intact
      vagus nerve. The excitation of neurons in the AP after IHS is partially dependent
      on vagal afferents, and the residual labeling that is present in the AP of
      neurectomized animals may be mediated via a blood-borne route.

PMID- 8760224
TI  - Lymphocytes and NK cell activity during repeated bouts of maximal exercise.
AB  - Effects on the immune system of 6-min "all-out" ergometer rowing were
      investigated over 2 days (2 x 3 bouts) in eight male oarsmen with a maximal
      oxygen uptake of 5.5 +/- 0.1 l/min (mean +/- SE). Blood samples were obtained
      before, during, and 2 h after each bout and on the day after the last bout.
      Compared with levels at rest, the first bout of exercise increased the
      concentration of leukocytes (2-fold); neutrophilic granulocytes (2-fold);
      lymphocytes (2-fold); monocytes (2-fold); the blood mononuclear cell (BMNC)
      subsets CD3+ (2-fold), CD4+ (2-fold), CD8+ (3-fold), CD16+ (8-fold), CD19+ (2
      fold), and CD14+ (2-fold); the NK cell activity (2-fold); and plasma interleukin
      6 (3-fold) (P < 0.05). During the last bout even higher levels were noted for
      leukocytes (3-fold); neutrophilic granulocytes (3-fold); lymphocytes (4-fold);
      the BMNC subsets CD4+ (3-fold), CD8+ (5-fold), CD16+ (13-fold), CD19+ (5-fold),
      and CD14+ (3-fold); and for the NK cell activity (4-fold) (P < 0.05). During the
      recovery periods all values were at or above the level at rest, and elevated
      concentrations of leukocytes (38%), neutrophilic granulocytes (48%), and
      lymphocytes (46%) reflected in the BMNC subsets and increased NK cell activity
      (119%) were also noted on the day after the last bout (P < 0.05). The results
      show that maximal exercise with large muscle groups provokes higher immune
      responses during repetitive bouts.

PMID- 8760227
TI  - First and second phases of biphasic fever: two sequential stages of the sickness
      syndrome?
AB  - We hypothesized that the systemic inflammatory response undergoes two consecutive
      stages, each characterized by different nonspecific sickness patterns. To test
      this hypothesis, we studied thermal, nociceptive, and motor responses to
      lipopolysaccharide (LPS) in 43 unanesthetized, habituated, and lightly restrained
      male Wistar rats previously implanted with a catheter in the jugular vein.
      Escherichia coli LPS was injected intravenously in a dose of 0, 0.1, 1, 10, 100,
      or 1,000 micrograms/kg. Colonic temperature (Tc) was measured with a
      thermocouple. Changes in nociception were assessed by tail flick latency (TFL) to
      a noxious heat stimulus. Motor activity was evaluated using an observation-based
      activity score (AS). The two lowest doses were apyrogenic. The next dose induced
      a monophasic fever with a maximal Tc rise of 0.9 +/- 0.2 degrees C at 108 +/- 11
      min post-LPS. The next two higher doses caused biphasic fevers with the first and
      second peaks of 0.7 +/- 0.1 and 1.4 +/- 0.1 degrees C (10 micrograms/kg) and 0.7
      +/- 0.1 and 1.4 +/- 0.2 degrees C (100 micrograms/kg) occurring at 60 +/- 6 and
      165 +/- 17 min and at 45 +/- 3 and 141 +/- 6 min, respectively. The highest dose
      of LPS resulted in a Tc fall (nadir, -0.6 +/- 0.1 degree C at 83 +/- 6 min). Two
      different sickness patterns were exhibited. The first (high Tc, low TFL and high
      AS) occurred during the monophasic fever and the first (early) phase of the
      biphasic fevers, and it was termed the early phase syndrome. The second pattern
      (high or low Tc, high TFL, and low AS) developed during the second (late) phase
      of the biphasic fevers and LPS-hypothermia (endotoxin shock), and it was termed
      the late phase syndrome. Occurring at different stages of the systemic
      inflammatory response and developing through different coping patterns
      [fight/flight (energy expenditure) vs. depression/withdrawal (energy
      conservation)], the two syndromes represent two different types of adaptation to
      infection and have different biological significance. Viewing sickness as a
      dynamic entity is justified clinically. Such a dynamic approach to the problem
      resolves several contradictions in the current concept of sickness.

PMID- 8760226
TI  - Mechanism of anoxia-induced atrial natriuretic peptide release in the isolated
      rat atria.
AB  - Our laboratory has recently shown that locally produced endothelin (ET) is
      involved in the atrial natriuretic peptide (ANP) response to a physical stimulus,
      stretch. The aim of this study was to determine if factors locally produced in
      the atria were involved in the ANP response to a chemical stimulus, anoxia.
      Reduced oxygen tension is a potent stimulus of ANP release, and our results show
      that, when isolated perfused atria were exposed to anoxic conditions, the ANP
      secretion rate increased by a maximum of 129 +/- 8% of the baseline. Exposure to
      anoxia caused neither an elevation in perfusate creatinine phosphokinase, a
      change in atrial morphology detectable by electron microscopy, nor interfered
      with the return toward the baseline ANP secretion rate with reoxygenation,
      suggesting that this response was not due to myocyte damage. When the atria were
      pretreated with either 3 microM BQ-123, an endothelin receptor inhibitor, or 10
      microM indomethacin, a cyclooxygenase inhibitor, the ANP response to anoxia was
      nearly abolished. To clarify the association between ET and prostaglandins, we
      showed that the ANP response to 50 nM ET-1 was totally blocked at both high and
      low pressure by 10 microM indomethacin, but the increased contractility response
      to ET was unaffected. Therefore, we have concluded that the anoxia-induced ANP
      response is mediated by locally produced ET, which, in turn, stimulates the
      production of prostaglandins. Prostaglandins appear to be responsible for the
      increased ANP secretion rate.

PMID- 8760228
TI  - Evidence for the existence of endothelin-B receptor subtypes and their
      physiological roles in the rat.
AB  - The physiological roles of endothelin-B (ETB) receptor subtypes in systemic and
      renal hemodynamics were assessed in conscious Sprague-Dawley rats. Mean arterial
      pressure, hindlimb flow, and renal blood flow were measured via an implanted
      catheter and pulsed Doppler flow probes. Bolus intravenous injections of
      sarafotoxin 6c (S6c), a selective ETB agonist, elicited transient dose-dependent
      vasodilation, followed by sustained vasoconstriction in the systemic bed, but
      only vasoconstriction in the renal bed. RES-701-1, a selective ETB antagonist,
      blocked the dilator and potentiated the constrictor effect; SB-209670, a mixed ET
      receptor antagonist, attenuated both responses to S6c. In follow-up studies, the
      role of endogenous ET was assessed by administration of the antagonists alone:
      RES-701-1, SB-209670, and the ETA-selective antagonist BQ-123. RES-701-1 unmasked
      a significant systemic and renal vasoconstriction, which was attenuated by SB
      209670 but not by BQ-123. SB-209670 and BQ-123 had no effect on basal hemodynamic
      parameters. Data from radioligand binding experiments showed that RES-701-1 binds
      with high affinity to the cloned human ETB receptor but poorly to the ETB
      receptor predominant in the rat kidney. Collectively, the results indicate that
      1) the vascular effects of ET in the rat are mediated by two ETB receptor
      subtypes: an RES-701-1-sensitive subtype, mediating vasodilation, and an RES-701
      1-insensitive subtype, mediating vasoconstriction; 2) the predominant role of
      endogenous ET is vasodilation; and 3) the ETA receptor plays a negligible role in
      the control of vascular tone in the rat.

PMID- 8760229
TI  - Expression of sarcoplasmic reticulum Ca(2+)-ATPase isoforms in marlin and
      swordfish muscle and heater cells.
AB  - The superior rectus muscles of marlin, swordfish, sailfish, and spearfish are
      modified for generating heat rather than force. This study focuses on the
      sarcoplasmic reticulum calcium-adenosinetriphosphatase (SR Ca(2+)-ATPase) to gain
      further insight into the muscle fiber type origin of the billfish "heater cell."
      Direct sequencing and immunolocalization demonstrated that marlin and swordfish
      epaxial swimming muscles express two forms of the SR Ca(2+)-ATPase in a fiber
      type-specific manner; red slow-twitch skeletal and cardiac muscles express the
      same SERCA2 message, whereas white fast-twitch skeletal muscles express a SERCA1
      message. Thus the expression pattern of the SR Ca2+ pump is similar in both
      billfish and tetrapod muscles. Molecular and immunological studies revealed that
      billfish heater tissue and superior rectus muscle express both fast and slow SR
      Ca2+ pump isoforms. Immunohistochemical results suggest that heater cells and
      most extraocular muscle fibers express the fast SR Ca2+ pump. Expression of the
      fast SR Ca(2+)-ATPase by heater cells has implications for heater cell origin and
      thermogenic control.

PMID- 8760230
TI  - Cardiac output and renal function during insulin hypertension in Sprague-Dawley
      rats.
AB  - Hyperinsulinemia has been reported to cause hypertension in rats; however, the
      renal and hemodynamic mechanisms are not known. In this study, changes in renal
      function, cardiac output (CO), and total peripheral resistance (TPR) were
      measured during chronic insulin infusion in eight rats (approximately 350 g).
      After a 4-day control period, a 7-day insulin infusion was begun (1.5 mU.kg-1.min
      1 iv), together with glucose (22 mg.kg-1.min-1 iv) to prevent hypoglycemia. Mean
      arterial pressure (MAP), CO, TPR, and heart rate were measured 24 h/day. MAP
      increased from 92 +/- 1 to 100 +/- 2 mmHg on day 1 and was 108 +/- 4 mmHg by day
      7 of insulin. CO tended to decrease during insulin infusion, although not
      significantly, averaging 94 +/- 4% of the control value of 121 +/- 7 ml/min.
      Heart rate did not change significantly from the control value of 384 +/- 8
      beats/min. TPR increased significantly to 122 +/- 11% of control by day 7. In
      five rats, glomerular filtration rate and effective renal plasma flow decreased
      to 73 +/- 4 and 66 +/- 5% of control, respectively, during insulin. Urinary
      sodium excretion averaged 2.6 +/- 0.1 and 2.7 +/- 0.1 meq/day during the control
      and insulin-infusion periods, respectively. These results indicate that insulin
      hypertension in rats is initiated by an increase in TPR rather than by increased
      CO. Also, the fact that sodium balance was maintained at elevated arterial
      pressure suggests that the ability of the kidneys to excrete sodium was impaired
      chronically during insulin infusion.

PMID- 8760231
TI  - Role of the renin-angiotensin system in mediating the effects of posture on renal
      function.
AB  - This study was designed to quantitate the influence of the neurohumoral
      activation associated with orthostatic stress on renal hemodynamics and sodium
      excretion and, furthermore, to determine the importance of the renin-angiotensin
      system in mediating these changes in renal function. Seven conscious dogs were
      studied while lying in the recumbent position and, subsequently, after standing
      in a supporting sling. Experiments were conducted under control conditions and
      after plasma angiotensin II (ANG II) concentration was fixed at control levels by
      chronic infusion of captopril (14 micrograms.kg-1.min-1) and ANG II (0.5 +/- 0.02
      ng.kg-1.min-1). During control experiments, 45 min of standing increased plasma
      renin activity twofold, whereas mean arterial pressure, heart rate, and plasma
      norepinephrine concentration remained unchanged. During standing, glomerular
      filtration rate (GFR) and renal plasma flow (RPF) fell to 88 +/- 2 and 77 +/- 3%
      of recumbent values, respectively, whereas filtration fraction (FF) increased 16
      +/- 1%. Additionally, urinary (UNaV) and fractional sodium excretion (FENa)
      decreased to 27 +/- 6 and 30 +/- 7% of recumbent values, respectively. When
      plasma ANG II concentration was fixed at control levels during standing, there
      were no significant changes in GFR, whereas increments in FF and reductions in
      RPF, UNaV, and FENa were attenuated by 63, 40, 30, and 33%, respectively. These
      data suggest that, in conscious dogs, standing in a supporting sling causes
      reflex activation of the sympathetic nervous and renin-angiotensin systems,
      eliciting reductions in GFR, RPF, and UNaV. Furthermore, ANG II contributes
      significantly to the effects of passive standing on renal hemodynamics and UNaV.

PMID- 8760232
TI  - Naltrexone induces arcuate nucleus neuropeptide Y gene expression in the rat.
AB  - Neuropeptide Y (NPY) has potent effects on several components of energy
      metabolism, including increased feeding and decreased brown fat thermogenesis.
      Negative energy balance, such as food deprivation, increases NPY mRNA in
      hypothalamic arcuate nucleus (ARC). Naltrexone (NLTX), an opioid receptor
      antagonist, decreases NPY-induced feeding. We hypothesized that NLTX would alter
      ARC NPY mRNA and change NPY effects on brown fat. Osmotic minipumps prefilled
      with either saline or NLTX (70 micrograms/h) were implanted subcutaneously in 32
      male Sprague-Dawley rats. One-half of the rats were food deprived and one-half
      were allowed food ad libitum for 48 h. Food intake was measured at 24 and 48 h.
      At 48 h, ARC NPY mRNA and brown fat uncoupling protein (UCP) mRNA levels were
      determined using cDNA probes. Forty-eight-hour food intake was significantly
      decreased by 24% after NLTX infusion. Food deprivation and NLTX treatment
      significantly and independently increased ARC NPY mRNA and decreased UCP mRNA
      levels in brown fat, suggesting a complex interaction between hypothalamic NPY
      and endogenous opioids in the regulation of energy balance.

PMID- 8760233
TI  - Characteristics of renal sympathetic nerve activity in sodium-retaining
      disorders.
AB  - Characteristics of renal sympathetic nerve activity in conscious rats with
      established congestive heart failure, cirrhosis, or nephrotic syndrome were
      analyzed using three methods: mean integrated voltage over time, power spectrum
      analysis, and sympathetic peak detection analysis. Compared with control rats,
      all three disease models had increased mean integrated voltage. On power spectrum
      analysis, all three disease models had increased relative power at the heart rate
      frequency, indicating that it was related to renal sympathetic nerve discharge
      coupled to the cardiac cycle. Congestive heart failure and nephrotic syndrome
      rats showed increased relative power in the low-frequency range, whereas
      cirrhotic and nephrotic syndrome rats showed decreased relative power in the high
      frequency range. On sympathetic peak detection analysis, the frequency of
      sympathetic peaks was greater in the three disease models compared with the
      control rats. In cirrhotic rats, the distribution of sympathetic peak heights was
      shifted toward an increased number of peaks of lesser height. It is concluded
      that basal renal sympathetic nerve activity is chronically increased in these
      disease models. This is manifest as increased power coupled to the cardiac cycle,
      which may reflect the disease-specific defects in arterial and cardiac baroreflex
      control. In cirrhosis, there is possible selective activation of a subgroup of
      renal sympathetic nerve fibers.

PMID- 8760234
TI  - Blockade of AT1 receptors enhances baroreflex control of heart rate in conscious
      rabbits with heart failure.
AB  - Because the renin-angiotensin system is activated in heart failure, we
      hypothesized that angiotensin II (ANG II) plays a role in altering baroreflex
      sensitivity in the setting of heart failure. Accordingly, we evaluated the
      baroreflex control of heart rate (HR) in conscious, chronically instrumented
      rabbits in the normal state and after the establishment of heart failure. Heart
      failure was induced by rapid ventricular pacing at a rate of 360-380 beats/min
      for an average of 14.5 +/- 1.4 days. The data were compared with normal rabbits
      instrumented in a similar fashion. Baroreflex curves were generated by inflation
      of implanted hydraulic occluders on the vena cava and aortic arch or by
      administration of phenylephrine and sodium nitroprusside. Experiments were
      carried out before and after intravenous administration of the AT1 antagonist L
      158,809. Rabbits with heart failure exhibited significantly lower arterial
      pressure (81 +/- 3 vs. 69 +/- 4 mmHg, P < 0.05), elevated resting HR (230 +/- 5
      vs. 260 +/- 10 beats/min, P < 0.05), and elevated left atrial pressure (3.6 +/-
      0.7 vs. 13.1 +/- 0.7 mmHg, P < 0.05). ANG II blockade had little effect on
      resting or baroreflex parameters in normal rabbits. However, in rabbits with
      heart failure, L-158,809 enhanced baroreflex sensitivity (2.7 +/- 0.5 vs. 4.7 +/-
      0.8 beats.min-1.mmHg-1; P < 0.05), primarily by increasing the minimum HR evoked
      during baroreceptor activation. beta 1-Blockade had no effect on any baroreflex
      parameter after L-158,809 in rabbits with heart failure. However, L-158,809
      significantly reduced the minimum HR after pretreatment with atropine in rabbits
      with heart failure. These data suggest that ANG II plays a role in modulation of
      cardiac sympathetic tone in this model of heart failure and may be responsible
      for the depressed baroreflex sensitivity observed in heart failure.

PMID- 8760235
TI  - Phosphodiesterases (PDEs) hydrolyze the 3' phosphoester bond of the purine 3',5'
      cyclic monophosphates, cAMP and cGMP.
AB  - Resistance to the natriuretic action of atrial natriuretic peptide (ANP) is a
      hallmark of states of pathological sodium retention including congestive heart
      failure, cirrhosis of the liver, and nephrotic syndrome. A variety of mechanisms
      including reduced delivery of filtrate to ANP-sensitive sites in the inner
      medullary collecting duct and diminished receptor density in this tubular segment
      have been offered to account for this resistance. Recent studies in experimental
      nephrotic syndrome and in liver disease produced by ligation of the common bile
      duct in rats suggest that increased activity of cyclic guanosine 3',5'
      monophosphate (cGMP) phosphodiesterase may be an important mediator of renal
      resistance to ANP. Such increased enzyme activity rapidly catabolizes the second
      messenger cGMP, normally formed when ANP interacts with its biologically active
      natriuretic peptide. A receptors, thereby leading to blunted ANP responsiveness.
      This increased phosphodiesterase activity offers a novel approach to the
      management of clinical conditions associated with sodium retention and edema
      formation.

PMID- 8760236
TI  - Phosphodiesterase activity as a mediator of renal resistance to ANP in
      pathological salt retention.
AB  - Resistance to the natriuretic action of atrial natriuretic peptide (ANP) is a
      hallmark of states of pathological sodium retention including congestive heart
      failure, cirrhosis of the liver, and nephrotic syndrome. A variety of mechanisms
      including reduced delivery of filtrate to ANP-sensitive sites in the inner
      medullary collecting duct and diminished receptor density in this tubular segment
      have been offered to account for this resistance. Recent studies in experimental
      nephrotic syndrome and in liver disease produced by ligation of the common bile
      duct in rats suggest that increased activity of cyclic guanosine 3',5'
      monophosphate (cGMP) phosphodiesterase may be an important mediator of renal
      resistance to ANP. Such increased enzyme activity rapidly catabolizes the second
      messenger cGMP, normally formed when ANP interacts with its biologically active
      natriuretic peptide A receptors, thereby leading to blunted ANP responsiveness.
      This increased phosphodiesterase activity offers a novel approach to the
      management of clinical conditions associated with sodium retention and edema
      formation.

PMID- 8760237
TI  - Aldosterone-dependent regulation of Na-K-ATPase subunit mRNA in the rat CCD:
      competitive PCR analysis.
AB  - In the cortical collecting duct (CCD), aldosterone increases the number of
      functionally active Na-K-adenosin-etriphosphatase (Na-K-ATPase) molecules by a
      mechanism involving an isoform-specific increase in the abundance of the Na-K
      ATPase alpha 1- and beta 1-subunit protein. However, the molecular basis for the
      response, particularly in the mammalian CCD in vivo, has remained unclear. To
      resolve this issue, reverse transcription (RT) and a competitive polymerase chain
      reaction (PCR) were employed to study mineralocorticoid-dependent regulation of
      alpha 1- and beta 1-subunit mRNA in the rat CCD. Na-K-ATPase subunit-specific
      oligonucleotides primers were used in the PCR to amplify reverse-transcribed
      subunit mRNA (RT-mRNA) from single microdissected CCD. Control templates were
      constructed (84-bp deletion mutation of the rat Na-K-ATPase alpha 1-subunit cDNA
      and 70-bp deletion of the beta 1-subunit cDNA), serially diluted, and coamplified
      with the wild-type Na-K-ATPase subunit RT-mRNA from single CCD. PCR products of
      predicted size were observed by ethidium bromide staining. Southern blots with an
      internal subunit-specific oligonucleotide confirmed Na-K-ATPase alpha 1- and beta
      1-subunit identity. The ratio of the amplified wild-type to mutant PCR products
      was found to be linear over the range of input control cDNA tested so that the
      amount of subunit mRNA could be determined. A chronic reduction in corticosteroid
      levels by bilateral adrenalectomy (7 days) reduced the apparent level of alpha 1
      subunit transcript by 54.0 +/- 6.3% but not the beta 1-subunit. Administering
      aldosterone to physiological levels is sufficient to restore CCD alpha 1-subunit
      mRNA abundance toward control levels within 6 h. We conclude the following: 1)
      regulation of Na-K-ATPase of CCD in vivo can be attributed, at least in part, to
      mineralocorticoid-dependent control of Na-K-ATPase alpha 1-subunit mRNA
      abundance; and 2) competitive PCR may provide a sensitive and quantitative tool
      for determining hormone-dependent regulation of mRNA abundance in nephron
      segments.

PMID- 8760238
TI  - Renal reserve during human pregnancy.
AB  - Pregnancy in healthy women is associated with increments in glomerular filtration
      rate (GFR) and effective renal plasma flow (ERPF). We hypothesized that the
      hyperfiltration of normal pregnancy attenuates or exhausts renal reserve. In 21
      healthy females studied serially in early and late pregnancy and then on average
      15 wk postpartum, GFR and ERPF were determined by inulin and p-aminohippurate
      clearances, respectively, before and during either an amino acid infusion (Vamin
      9; Kabi Pharmacia) (n = 14) or a control infusion of Hartman's solution (n = 7),
      both infused at 4 ml/min for 210 min. In early and late pregnancy, GFR increased
      significantly in response to amino acid infusion [from 137 +/- 29 to 162 +/- 35
      ml/min (P < 0.001) and from 134 +/- 29 to 148 +/- 40 ml/min (P < 0.01),
      respectively], with the increments (18 and 10%, respectively) not significantly
      different from postpartum (non-pregnant) when GFR increased by 12% from 94 +/- 22
      to 105 +/- 23 ml/min (P < 0.002). Amino acid infusion significantly increased
      ERPF from 874 +/- 188 to 980 +/- 215 ml/min in early pregnancy (P < 0.01), from
      684 +/- 135 to 773 +/- 181 ml/min in late pregnancy (P < 0.01), and from 507 +/-
      121 to 560 +/- 141 ml/min postpartum (P < 0.006), increments of 12, 13, and 10%,
      respectively. GFR did not change in response to control infusion. We conclude
      that, despite gestational increments in renal hemodynamics of > 40%, pregnancy
      does not attenuate the renal response to amino acid infusion.

PMID- 8760239
TI  - Extracellular chloride regulates mesangial cell calcium response to vasopressor
      peptides.
AB  - The role of extracellular chloride in the regulation of mesangial cell calcium
      responsiveness to vasopressor peptides was explored. First, the components of
      vasopressor-stimulated calcium signaling were defined in rat mesangial cells
      cultured on coverslips and preloaded with fura 2. By spectrofluorometry,
      manganese uptake (reflecting divalent cation channel activation) was observed by
      quenching of fura 2, or intracellular cytosolic calcium concentration was
      calculated by dual-excitation ratiometric measurement. In cells depolarized with
      KCl (45 mM), enhanced manganese uptake or increased cytosolic calcium were
      inhibited with verapamil (10 microM). Pretreatment of mesangial cells with
      verapamil reduced the sustained calcium level in response to endothelin-1 (0.1
      microM) by 65 +/- 6% (means +/- SE, n = 12) and to vasopressin (1 microM) by 62
      +/- 12% (n = 8). Perforated cell patch-clamp measurement confirmed that
      endothelin-1 stimulated a sustained increase in cytosolic calcium or divalent
      cation entry only in the presence of simultaneous depolarization. In chloride
      free buffer (chloride replaced with impermeant anions), sustained calcium
      response to endothelin-1 was reduced by 72 +/- 8 (n = 8) and by 65 +/- 4% (n = 8)
      in the presence of the chloride channel inhibitor, 5-nitro-2-(3
      phenylpropylamino)benzoic acid (55 microM). In chloride-free buffer, cytosolic
      calcium (unstimulated) increased to > 200 nM by 30 min. These data indicate that
      reduced extracellular chloride increases mesangial cell basal cytosolic calcium
      and decreases the transient and sustained cytosolic calcium response to
      vasopressor peptides.

PMID- 8760240
TI  - Expression and localization of prostaglandin EP3 receptor mRNA in the immature
      rabbit kidney.
AB  - Arginine vasopressin (AVP)-stimulated cAMP generation is decreased in the
      immature collecting duct (CD). This is the result of prostaglandin antagonism,
      most likely via the inhibitory guanine nucleotide-binding protein (Gi). The EP3
      subtype prostaglandin E2 (PGE2) receptor, which is coupled to Gi, could mediate
      this effect. We studied the developmental expression of EP3 receptor in the
      rabbit kidney. Higher levels of EP3 mRNA were observed in the immature kidney
      using three different assays: 1) reverse transcription-polymerase chain reaction
      (RT-PCR) with internal standard, 2) competitive PCR, and 3) ribonuclease
      protection assay. The highest levels were observed at 2 wk of age. RT-PCR from
      isolated nephron segments detected EP3 mRNA in the medullary thick ascending
      limb, cortical CD (CCD), and inner medullary CD (IMCD) of adult and immature
      kidneys. We conclude that 1) renal expression of EP3 mRNA is increased in
      immature kidneys and 2) EP3 mRNA is localized in the distal nephron. This
      suggests that EP3 receptor may play a role in the regulation of distal tubular
      transport during development.

PMID- 8760241
TI  - Genomic structure and regulation of Kcn1, a cGMP-gated potassium channel.
AB  - We recently cloned a novel rabbit gene that encodes a 725-amino acid protein
      (Kcn1) (Y. Yao, A. S. Segal, P. Welling, X. Zhang, C. M. McNicholas, D. Engel, E.
      L. Boulpaep, and G. Desir. Proc. Natl. Acad. Sci. USA 92: 11711-11715, 1995).
      Kcn1 RNA injected in Xenopus oocytes leads to the expression of potassium
      channels that are specifically activated by guanosine 3',5'-cyclic monophosphate
      (cGMP). Northern blot and ribonuclease (RNase) protection analysis show that Kcn1
      is differentially expressed in kidney, aorta, brain, and heart. The purpose of
      present study is to determine the structure of Kcn1 gene, analyze the promoter
      region, and identify cis-regulatory elements responsible for transcription. We
      find that the coding region of Kcn is intronless. The major transcription
      initiation site was identified by primer extension. Sequence analysis of the 5'
      flanking region indicates that, although the gene lacks a typical TATA box, it
      does have a TATA-box-like region (-TAT-). Using luciferase reporter constructs
      transfected in the porcine kidney cell line (LLC-PK1), the promoter region and a
      5' enhancer element were identified by deletion analysis. Phorbol esters (12-O
      tetradecanoylphorbol-13-acetate) and forskolin stimulated Kcn1 gene expression
      2.5- and 3.5-fold, respectively. In conclusion, we have identified the region of
      the novel potassium channel gene, Kcn1, that contains the promoter, a 5'
      enhancer, and several cis-regulatory elements and shown that gene transcription
      is stimulated by cAMP and phorbol esters.

PMID- 8760242
TI  - Tubulogenesis from isolated single cells of adult mammalian kidney: clonal
      analysis with a recombinant retrovirus.
AB  - The adult mammalian kidney tubule epithelium exists in a relatively dormant,
      slowly replicative state but has a large potential for regenerative morphogenesis
      following severe ischemic or toxic injury. Under selective serum-free growth
      conditions, which included epidermal growth factor and retinoic acid, a
      subpopulation of renal proximal tubule cells isolated from adult rabbit kidney
      were grown in cell culture. These cells possessed two important characteristics:
      1) an ability to differentiate morphogenically into tubule structures when grown
      in three-dimensional collagen gels and 2) a high capacity for self-renewal, since
      cell lineage analysis with a recombinant retrovirus demonstrated that in vitro
      tubulogenesis arose from clonal expansion of a single cell. Thus individual cells
      in the adult kidney have retained the ability for kidney tubulogenesis in vitro.

PMID- 8760243
TI  - A ureteric bud cell line induces nephrogenesis in two steps by two distinct
      signals.
AB  - Nephrons develop from mesenchymal cells that have contacted the ureteric bud
      (UB). To determine whether cell associated or secreted ureteric molecules induce
      the mesenchyme, we have isolated UB cell lines from mice transgenic for T
      antigen. These cells express epithelial and ureteric (Dolichos lectin staining, c
      ret, c-met without hepatocyte growth factor) specific markers, which identifies
      them as authentic UB cells. Medium conditioned by our cells rescues mesenchyme
      from apoptosis without inducing the appearance of epithelial aggregates. The same
      was found by culturing mesenchymes upon the apical surface of a UB monolayer. In
      contrast, tubules were induced in mesenchymes contacting trypsinized pellets of
      UB cells. As revealed by staining for T antigen and Dolichos lectin or by
      prelabeling UB cells with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine
      perchlorate (DiI), we found that our cells encapsulated the mesenchyme but did
      not incorporate in the tubules. These data demonstrate that nephrogenesis is
      stimulated by two distinct ureteric signals, secreted molecules rescue the
      mesenchyme from apoptosis, whereas diffusion-limited basolateral molecules
      trigger mesenchymal/epithelial conversion.

PMID- 8760244
TI  - Quantitation of aquaporin-2 abundance in microdissected collecting ducts: axial
      distribution and control by AVP.
AB  - Aquaporin-2 (AQP-2) is the arginine vasopressin-regulated water channel of the
      renal collecting ducts. Using an improved version of a fluorescence-based enzyme
      linked immunosorbent assay (Y. Maeda, B. L. Smith, P. Agre, and M. A. Knepper. J.
      Clin. Invest. 95: 422-428, 1995), we quantified AQP-2 protein abundance in
      microdissected renal collecting ducts from normal Sprague-Dawley (SD) rats and
      vasopressin-deficient Brattleboro rats. Standard curves were linear in the range
      of 0-200 fmol/well and were highly reproducible from day to day (lower limit of
      detection 2.3 fmol; coefficient of variation 6-9%). In SD rats thirsted for 24 h,
      the measured quantities of AQP-2 were as follows (x 10(9) molecules/mm): cortical
      collecting ducts (CCD), 4.3 +/- 0.5; outer medullary collecting ducts (OMCD),
      10.1 +/- 1.7; initial one-third of inner medullary collecting duct (IMCD-1), 9.2
      +/- 1.1; middle one-third of the IMCD (IMCD-2), 7.5 +/- 0.8; terminal one-third
      of the IMCD (IMCD-3), 3.3 +/- 0.6; n = 7-12. In IMCD-2 this corresponds to 11.8
      +/- 1.3 x 10(6) AQP-2 molecules per cell. Thus AQP-2 is extremely abundant in
      collecting duct cells. AQP-2 levels were decreased in untreated Brattleboro rats
      relative to the parent strain Long-Evans (LE) by 68% in IMCD-2 and 44% in CCD.
      Following vasopressin infusion by osmotic minipumps, AQP-2 levels in IMCD-2 of
      Brattleboro rats rose gradually, reaching levels equivalent to those seen in LE
      rats after 5 days. A similar rise was seen in the CCD, indicating that the
      vasopressin-induced increase was not dependent on a large increase in the
      interstitial tonicity. Thus a rise in circulating vasopressin concentration
      increases the level of AQP-2 protein expression in collecting ducts, presumably
      via a direct action of vasopressin.

PMID- 8760245
TI  - Beta 2-adrenergic function in cultured rat proximal tubule epithelial cells.
AB  - We conducted studies to determine whether functional beta 2-adrenoceptors are
      present in cultured rat proximal tubule epithelial cells. To determine whether
      cultured cells maintain polarity with respect to sodium transport, cells were
      acid loaded. Acid loading resulted in stimulation of sodium transport. Exposure
      of acid-loaded cells to alkaline extracellular pH further enhanced sodium
      transport (22Na flux at pH 7.50 was 68.1 +/- 44% above pH 7.00, P < 0.05).
      Cultured proximal tubules also exhibited basolateral 86Rb uptake, 65% of which
      was ouabain sensitive. Thus cultured cells maintain apical Na/H antiport and
      basolateral Na-K-adenosinetriphosphatase (Na-K-ATPase). Metaproterenol (10(-6)
      M), a selective beta 2-agonist, stimulated Na-K-ATPase activity by 36 +/- 6%
      above control (P < 0.05). The stimulatory effect was blocked by ICI-118551, a
      selective beta 2-antagonist. To determine whether metaproterenol-dependent
      increases in Na-K-ATPase were dependent on apical sodium entry, apical entry was
      blocked with dimethylamiloride or maximized with monensin. Both dimethylamiloride
      and monensin prevented metaproterenol activation of Na-K-ATPase. Metaproterenol
      mediated increases in Na-K-ATPase activity were associated with increases in
      sodium transport (27 +/- 10% above control, P < 0.05), which was prevented by
      dimethylamiloride. In contrast to isoproterenol, metaproterenol did not stimulate
      cAMP production. In summary, we have shown that functional beta 2-adrenoceptors
      are present on cultured rat proximal tubules. beta 2-Adrenoceptor activation
      results in increases in Na-K-ATPase and Na transport as a consequence of
      increased apical sodium entry.

PMID- 8760246
TI  - Differential regulation of kallikrein, kininogen, and kallikrein-binding protein
      in arterial hypertensive rats.
AB  - This study was designed to determine whether the kallikrein-kinin system exerts a
      protective action in hypertension induced by chronic inhibition of nitric oxide
      synthase. N omega-nitro-L-arginine methyl ester (L-NAME, 40 mg/100 ml water) was
      given orally to Sprague-Dawley rats, while controls received regular tap water.
      Hepatic kininogen mRNA levels in the L-NAME-treated group were 2.9- and 2.5-fold
      higher at 3 and 4 wk, respectively, compared with control rats, whereas
      kallikrein-binding protein (KBP) mRNA levels were 82% and 45% of the values found
      in control rats at 3 and 4 wk, respectively. There was no significant change in
      hepatic alpha 1-antitrypsin mRNA levels under the same conditions. At 3 and 4 wk
      post L-NAME treatment, renal kallikrein mRNA levels were 2.5- and 3.4-fold higher
      than in controls, whereas renal beta-actin mRNA levels were similar between
      groups. Changes in the transcript levels of renal kallikrein, kininogen, and KBP
      were consistent with their protein levels. Immunoreactive total kininogen and low
      Mr kininogen levels in sera and tissue kallikrein levels in kidney were
      significantly higher in the L-NAME-treated group, whereas KBP levels in the
      circulation were lower compared with controls. Systolic blood pressure was
      increased by 58 +/- 4 mmHg after 4 wk of L-NAME treatment. This effect was
      enhanced in rats given L-NAME in combination with HOE-140, a bradykinin B2
      receptor antagonist, at the dose of 100 micrograms/day ip (79 +/- 5 vs. 58 +/- 4
      mmHg, P < 0.05). This difference was confirmed by direct measurement of mean
      blood pressure (MBP). An intra-arterial bolus injection of 200 ng bradykinin
      significantly decreased MBP of L-NAME-treated rats, and this effect was blunted
      in the group treated with the bradykinin antagonist (-29 +/- 3 vs. -9 +/- 2 mmHg,
      P < 0.01). These results suggest that enhanced kallikrein and kininogen synthesis
      may have a protective role against the cardiovascular effects induced by chronic
      inhibition of nitric oxide synthesis.

PMID- 8760247
TI  - Afferent arteriolar response to arachidonic acid: involvement of metabolic
      pathways.
AB  - Arachidonic acid (AA) metabolites have been implicated in the control of renal
      hemodynamics, but the nature of the metabolites produced by renal cells when AA
      is released has remained uncertain. Experiments were performed using the in vitro
      perfused juxtamedullary nephron preparation to examine the effects of perfusion
      and superfusion of AA on the renal microvasculature. Extraluminal exposure of the
      vessels by superfusion with solutions containing 0.1, 1.0, and 10 microM AA
      decreased afferent arteriolar diameter by 8 +/- 2, 16 +/- 3, and 20 +/- 3%,
      respectively. The same doses of AA added to the perfusate produced a similar
      afferent arteriolar vasoconstriction. Inhibition of the major enzymatic pathways
      unmasked differential responses of AA that were dependent on the direction from
      which the vasculature was exposed to AA. 17-Octadecynoic acid (1 microM), an
      inhibitor of the cytochrome P-450 pathway, eliminated the vasoconstrictor
      response to superfused AA but had little effect on the response to perfused AA.
      Lipoxygenase inhibition with baicalein (0.5 microM) did not alter the afferent
      arteriolar vasoconstriction during superfusion with AA but did attenuate the
      vasoconstrictor response to perfused AA by 34%. Cyclooxygenase inhibition with 10
      microM indomethacin reduced the afferent arteriolar response to superfusion with
      10 microM AA by 46%, but the responses to perfusion with AA were reversed,
      leading to the unmasking of a 17% afferent arteriolar dilation. The AA-induced
      vasorelaxation observed during cyclooxygenase inhibition was prevented by the
      subsequent addition of a P-450 inhibitor. Additionally, after endothelial removal
      with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), the
      vasodilatory response reverted to a vasoconstriction. The results of this study
      demonstrate that in the rat, AA metabolites exert predominant actions on afferent
      arterioles, but differential responses are mediated via different enzymatic
      pathways depending on the origin of AA. Increased AA availability of intraluminal
      origin leads to production of cyclooxygenase-derived vasoconstrictor metabolites
      and also to endothelial-derived cytochrome P-450 vasodilatory metabolites. In
      contrast, increased AA availability of interstitial origin leads to production of
      vasoconstrictor cytochrome P-450 metabolites.

PMID- 8760248
TI  - Transcriptional and posttranscriptional mechanisms regulate human renin gene
      expression in Calu-6 cells.
AB  - We have recently identified a human pulmonary carcinoma cell line (Calu-6) that
      expresses human renin (hREN) mRNA endogenously, and we use it herein as a model
      to examine the regulation of the hREN gene. Transfection analysis of a deletion
      series (-2750 to -149) of hREN promoter-luciferase fusion constructs revealed the
      presence of multiple weak regulatory elements within the first 1,301 bp of the 5'
      flanking region and a classic silencer element within the first intron (intron A)
      of the gene. The 5'-flanking regulatory domain consisted of three closely linked
      elements, two negative and one positive, each contributing a cell-specific
      threefold modulation of transcriptional activity. Treating Calu-6 cells with
      forskolin caused a 100-fold increase in steady-state endogenous hREN mRNA but no
      increase in hREN promoter activity in transient transfections or in nuclear
      runoff transcription assays. Nevertheless, de novo transcription and translation
      were necessary for adenosine 3',5'-cyclic monophosphate (cAMP)-mediated
      induction. Our results suggest that multiple regulatory elements regulate basal
      transcriptional activity of the hREN gene and the increase in hREN mRNA by cAMP
      may be mediated by posttranscriptional mechanisms.

PMID- 8760249
TI  - Characterization and distribution of albumin binding protein in normal rat
      kidney.
AB  - The mechanism by which proteins that pass through the glomerular basal lamina are
      taken up by proximal tubule cells is incompletely characterized. Past work has
      identified the kinetics of albumin binding to renal brush-border membrane. We
      have now purified and characterized albumin binding protein (ABP) and shown its
      distribution in renal proximal tubular cells. ABP was purified from rat renal
      proximal tubular cell brush-border membrane by affinity chromatography with rat
      serum albumin-Sepharose. The resulting ABP had two apparent molecular masses (55
      and 31 kDa) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
      Antibodies to ABP were raised in rabbits and checked by immunoassay and
      immunoblotting. Light-microscopic immunohistochemistry showed ABP all along the
      proximal tubule in the pars convoluta and pars recta. Electron-microscopic
      immunohistochemistry showed labeling on microvilli and in apical endocytic
      vacuoles, dense apical tubules, and lysosomes. These results indicate that ABP is
      involved in proximal tubule endocytosis.

PMID- 8760250
TI  - PDGF and IL-1 induce and activate specific protein kinase C isoforms in mesangial
      cells.
AB  - In vitro and in vivo data suggest a remarkable plasticity in the differentiated
      phenotype of intrinsic glomerular cells, which after injury express new
      structures and functions. We have shown that a protein kinase C (PKC) isoform,
      beta II, is expressed in diseased but not normal glomeruli. Since intrarenal
      cytokine synthesis has been implicated in the pathogenesis of progressive
      glomerular injury, we have hypothesized that these mediators induce a change in
      isoform profile. To test this hypothesis in vitro, we have determined whether
      platelet-derived growth factor (PDGF) and interleukin-1 (IL-1) alter the
      expression or activation of PKC isoforms in cultured mesangial cells (MCs). By
      immunoblot and ribonuclease (RNase) protection assays, both PDGF and IL-1 induce
      as early as 2 h de novo synthesis of PKC-beta II. Since MCs constitutively
      express PKC-alpha, -beta I, and -zeta, we also determined whether IL-1 or PDGF
      alter the activity of these isoforms. PDGF maximally induced translocation of PKC
      alpha (10 min), -beta I (90 min), -epsilon (120 min), and -zeta (120 min) from
      the cytosolic to the membrane fraction. IL-1, in contrast, did not alter the
      distribution of alpha, beta I, or epsilon at any time measured but did induce PKC
      zeta translocation. These data suggest inflammatory mediators regulate PKC
      isoform activity in diseased glomeruli both by de novo synthesis of unexpressed
      isoforms and by activation of constitutively expressed PKC isoforms.

PMID- 8760251
TI  - Insulin resistance but IGF-I sensitivity in chronic renal failure.
AB  - The effects of insulin-like growth factor I (IGF-I) and insulin on glucose
      metabolism were compared in awake, chronically catheterized rats with chronic
      renal failure (CRF) and sham-operated, pair-fed controls. In control rats, IGF-I
      (5 micrograms.kg-1.min-1) and insulin (2 mU.kg-1.min-1) infusions produced
      similar twofold increases in total body glucose uptake from fasting values under
      euglycemic conditions (euglycemic clamps). Total body glucose uptake during
      euglycemic IGF-I clamps at 5 and 10 micrograms.kg-1.min-1 was not different
      between CRF and control rats. Total body glucose uptake during euglycemic insulin
      clamps at 2 and 4 mU.kg-1.min-1 was significantly lower in CRF rats compared with
      corresponding values in control rats. Hepatic glucose production was suppressed
      by insulin equally but not by IGF-I in both groups. Correction of metabolic
      acidosis by NaHCO3 partially improved insulin resistance in rats with CRF,
      whereas an equimolar amount of NaCl had no effect. Thus the capacity of IGF-I
      infusion to stimulate total body glucose uptake is maintained in CRF rats that
      are insulin resistant.

PMID- 8760252
TI  - Transforming growth factor-beta modulation of the alpha 1(IV) collagen gene in
      murine proximal tubular cells.
AB  - We have examined the expression of the alpha 1(IV) collagen gene in murine
      proximal tubular cells (MCT) to better understand how it is regulated in
      parenchymal cells. Transcriptional activity was examined using luciferase
      reporters driven by the alpha 1(IV) promoter and varying lengths of 5'-flanking
      sequences. The minimal bidirectional promoter showed low intrinsic activity in
      MCT cells, but addition of upstream sequences increased luciferase expression.
      Maximal activity resided within the first 1,200 bp upstream. A minigene construct
      was generated by placing a portion of the alpha 1(IV) first intron downstream
      from the promoter region. The intronic sequences significantly decreased activity
      of the promoter in MCT cells and 3T3 fibroblasts but greatly enhanced expression
      in murine parietal yolk sac (PYS) endodermal cells. Addition of transforming
      growth factor-beta (TGF-beta) to MCT cultures elevated the levels of secreted
      type IV collagen. Treatment of either transiently or stably transfected MCT cells
      with TGF-beta produced an increase in the levels of expression of all of the
      reporters tested. These data support the hypothesis that cell-specific regulation
      of alpha 1(IV) collagen is dependent upon downstream sequences, which act to
      decrease the expression of type IV collagen in tubular epithelium. The activity
      of the alpha 1(IV) collagen gene in proximal tubular cells is increased by TGF
      beta, which acts on the domain(s) embedded within the intergenic bidirectional
      promoter.

PMID- 8760253
TI  - The 3'-nontranslated region of rat renal glutaminase mRNA contains a pH
      responsive stability element.
AB  - Rat kidney expresses two forms of glutaminase (GA) mRNA which probably result
      from the use of alternative polyadenylation signals. The two mRNAs are increased
      coordinately in response to metabolic acidosis via a mechanism that apparently
      does not involve transcriptional or translational regulation. A 956-bp fragment
      that contains the 3'-nontranslated sequence of the smaller GA cDNA was cloned
      into an expression vector (p beta G) that encodes a chimeric beta-globin growth
      hormone mRNA. Both the parent and the derived construct (p beta G-GA) were
      transfected into LLC-PK1-F+ cells. Stable transfectants express sixfold lower
      levels of beta G-GA mRNA than that of the parent beta G mRNA. However, only the
      beta G-GA mRNA is increased 2.5-fold by growth in acidic medium (pH 6.9, 10 mM
      HCO3-). The apparent half-life of the beta G mRNA (> 24 h) is unaffected by the
      pH of the growth media. In contrast, the apparent half-life of the beta G-GA mRNA
      is increased from 4.5 h to approximately 24 h when cells are transferred to
      acidic medium for 8 h. The observed pH response is not reproduced when the beta G
      GA construct is stably transfected into COS-7 cells or when a beta-globin
      phosphoenolpyruvate carboxykinase chimeric gene is expressed in LLC-PK1-F+ cells.
      Thus the 3'-nontranslated region of the GA mRNA contains a pH-responsive
      stability element.

PMID- 8760254
TI  - Dietary HCO3 reduces distal tubule acidification by increasing cellular HCO3
      secretion.
AB  - We examined the components of net HCO3 reabsorption (H+/HCO3 secretion and
      transepithelial HCO3 permeability) in in vivo perfused distal tubules of
      anesthetized rats to determine the mechanisms by which dietary HCO3 reduces
      acidification in this nephron segment. Animals eating a minimum electrolyte diet
      drank either (in mM) 80 NaHCO3, 80 NaCl, or 40 Na2SO4 for 7-10 days and were
      compared with controls drinking distilled H2O. On perfusion with a HCO3- and Cl- 
      containing solution, net HCO3 reabsorption was lower than control in only the
      NaHCO3 animals (14.4 +/- 1.3 vs. 4.1 +/- 0.5 pmol.mm-1.min-1, P < 0.001). On
      perfusion with a 0 HCO3-0 Cl- solution, distal tubule luminal HCO3 accumulation
      (JHCO3) was higher in NaHCO3 animals than control (-13.7 +/- 1.3 vs. -4.7 +/- 0.7
      pmol.mm-1.min-1, P < 0.002). Despite a higher JHCO3, estimated transepithelial
      HCO3 permeability in the NaHCO3 animals was similar to control [0.52 +/- 0.06 vs.
      0.36 +/- 0.04 x 10(-7) cm2/s, P = not significant (NS)]. Luminal acetazolamide
      (Az) reduced JHCO3 in NaHCO3 animals to a level similar to control (-6.2 +/- 0.6
      vs. -4.0 +/- 0.5 pmol.mm-1.min-1, P = NS) in this nephron segment containing
      cells with cytoplasmic but no luminal carbonic anhydrase activity. Including Cl-
      in the initial perfusate increased JHCO3 in NaHCO3 animals only (-20.8 +/- 1.9
      vs. -13.7 +/- 1.3 pmol.mm-1.min-1, P < 0.02), and this increase was inhibited by
      luminal Az. Calculated H+ secretion was similar among groups. Together, the data
      indicate that dietary HCO3 reduces distal tubule acidification by increasing Az
      sensitive generation of HCO3 by distal tubule cells that enters the lumen by a
      mechanism augmented by luminal Cl-.

PMID- 8760255
TI  - Effects of angiotensin II on electrolyte transport in the early and late distal
      tubule in rat kidney.
AB  - We have demonstrated in previous studies that luminal administration of low doses
      of angiotensin II (ANG II) stimulate and high doses of ANG II inhibit fluid and
      HCO3- transport in proximal tubules of rat kidney. However, the role of ANG II on
      Na+ and HCO3- transport in the distal nephron has not yet been fully elucidated.
      The superficial early and late distal tubules (DT) of the nephron segments
      correspond to the distal convoluted tubule and initial collecting tubule.
      Accordingly, we investigated the effects of ANG II on Na+, HCO3-, and K+
      transport in the early and late DT by separate perfusion of these tubule segments
      in vivo. [3H]inulin, Na+, K+, and total CO2 concentrations were measured in the
      perfusate and collected fluid, and transport of sodium (JNa), bicarbonate
      (JHCO3), potassium (JK), and fluid (JV) were analyzed as an index of the hormone
      effect. Intravenous infusion of the ANG II receptor antagonist [Sar1,Ile8]ANG II
      (1 microgram.kg-1.min-1) decreased JV, JNa, and JHCO3 in the early DT and
      decreased Jv and JNa in the late DT. Addition of ANG II (10(-11) M) to the
      tubular perfusate significantly increased the Jv, JNa, and JHCO3 in the early DT.
      Similar studies in late DT demonstrated an increase in Jv and JNa, decrease in
      JK, but no effect on JHCO3. The effects of ANG II on fluid and ion transport were
      abolished by the luminal application of amiloride (10(-3) M) and of the
      angiotensin-receptor blocker [Sar1,Ile8]ANG II (10(-6) M). These results suggest
      that ANG II stimulates Na+/H+ exchange in the early DT (distal convoluted tubule)
      and amiloride-sensitive Na+ transport (Na+ channels) in the late DT (initial
      collecting tubule) of cortical nephrons.

PMID- 8760256
TI  - Alpha 2-adrenergic-mediated inhibition of water and urea permeability in the rat
      IMCD.
AB  - These studies were conducted to determine whether the alpha 2-agonists
      epinephrine and dexmedetomidine inhibit osmotic water permeability (Pf) and urea
      permeability (Pu) in the rat inner medullary collecting duct (IMCD). Wistar rat
      IMCD segments were perfused via standard methods, and Pf and Pu were determined
      in separate studies. The control period was followed by adding 220 pM arginine
      vasopressin (AVP) or 10(-4) M dibutyryladenosine 3',5'-cyclic monophosphate
      (DBcAMP) to the bath. Epinephrine or dexmedetomidine, both at 1 microM, was then
      added to the bath, and this period was followed by adding 1 microM atipamezole, a
      selective alpha 2-antagonist. The phosphodiesterase inhibitor 3-isobutyl-1
      methylxanthine was present in all experiments with DBcAMP. Epinephrine inhibited
      AVP- and DBcAMP-stimulated Pf by 90% and 80%, respectively. Dexmedetomidine
      inhibited AVP- and DBcAMP-stimulated Pf by 98% and 97%, respectively. Epinephrine
      inhibited AVP- and DBcAMP-stimulated Pu by 70% and 60%, respectively.
      Dexmedetomidine failed to affect Pu. Atipamezole reversed all inhibitory effects.
      These data confirm an alpha 2-mediated mechanism in the IMCD that modulates Pf
      and Pu, and they indicate that inhibition occurs via post-cAMP cellular events.

PMID- 8760257
TI  - Coupling of entry to exit by peritubular K+ permeability in a mathematical model
      of rat proximal tubule.
AB  - In the proximal tubule in vivo, glomerulotubular balance requires that tubule
      epithelial cells accommodate a twofold variation in Na+ reabsorption through the
      Na+/H+ exchanger of the luminal membrane. In a mathematical model of proximal
      tubule, in which permeability coefficients are fixed, doubling flux through the
      Na+/H+ antiporter produces a substantial increase in cell volume and cytosolic
      HCO3-. In this model, it is possible to vary peritubular K+ permeability with
      changes in luminal Na+ entry, so that cell volume is constrained to be constant.
      In these calculations, the model predicts that peritubular hyperpolarization and
      nearly constant cytosolic HCO3- will accompany increases in luminal Na+ entry.
      Realistic models of variable peritubular K+ permeability might include a
      functional dependence on flux through the Na(+)-K(+)-adenosinetriphosphatase,
      cytosolic pH, or cell volume. When K+ permeability is represented as a function
      of any of these variables, homeostatic control of cell volume and pH can be
      obtained over a physiological variation of Na+/H+ flux. However, when luminal Na+
      entry is via Na(+)-glucose cotransport, volume homeostasis is best when
      peritubular K+ permeability depends on the rate of active Na+ transport. For any
      modulator of K+ permeability, realistic constraints on the value of this
      parameter suggest that peritubular K+ permeability is, by itself, not sufficient
      to maintain cell volume within narrow limits. Parallel activation of another exit
      pathway, such as peritubular Na(+)-3 HCO3- cotransport, may be required to
      achieve the necessary homeostasis.

PMID- 8760259
TI  - Abnormal postpartum renal development and cystogenesis in the bcl-2 (-/-) mouse.
AB  - Mice deficient for B cell leukemia/lymphoma gene 2 [bcl-2(-/-) mice] manifest
      congenital renal hypoplasia and develop multicystic kidney disease and renal
      failure postnatally. To characterize postpartum renal development, to identify
      the cellular origin of the cysts, and to provide insight into the role that bcl-2
      deficiency plays in the cystogenic process, we examined the morphology of kidneys
      from bcl-2 (-/-) mice and wild-type littermates [bcl-2 (+/+)] from birth (P0) to
      postpartum day 28 (P28), determined whether abnormalities of cellular
      proliferation and apoptosis accompany cyst development, and characterized
      expression of the bcl-2-related protein, bax. Between P0 and P7, kidneys from bcl
      2 (-/-) and bcl-2 (+/+) mice undergo a comparable increase in weight and have
      similar histological appearances. However, during the next 2 wk of life, weight
      gain in kidneys from bcl-2 (-/-) mice is reduced compared with that in kidneys
      from bcl-2 (+/+) animals, and cysts develop in tubules with staining
      characteristics of proximal tubule, distal tubule/medullary thick ascending limb
      of Henle's loop, and collecting duct. Unaffected glomeruli and proximal tubules
      in kidneys of bcl-2 (-/-) mice undergo compensatory growth. Cystogenesis is
      accompanied by enhanced incorporation of 5-bromo-2'-deoxyuridine in cells within
      cortex and medulla and apoptosis of cells within cysts and in the renal
      interstitium. Bax protein is expressed in the distal tubule in kidneys of bcl-2
      (+/+) and bcl-2 (-/-) mice and in some, but not all cysts. We conclude that
      abnormal regulation of DNA synthesis and apoptosis accompany cystogenesis in bcl
      2 (-/-) mice during postpartum kidney development. Continued expression of bax
      could enhance apoptotic cell death.

PMID- 8760258
TI  - Expression of aquaporins-1 and -2 during nephrogenesis and in autosomal dominant
      polycystic kidney disease.
AB  - Aquaporin-1 (AQP1), located in proximal tubules (PT) and descending thin limbs of
      Henle (DTL), and aquaporin-2 (AQP2), located in collecting ducts (CD), are
      channels involved in water transport across renal tubule epithelia. Using
      antibodies against AQP1 and AQP2, we here show expression of AQP1 and AQP2 in
      normal human developing and adult kidneys and in autosomal dominant polycystic
      kidney disease (ADPKD). Unlike in rats, AQP1 and AQP2 are expressed early during
      human nephrogenesis (12-wk gestation). AQP1 was first seen in developing PT
      epithelia, predominantly in apical cell membranes, and, at 15 wk, was also
      detected in DTL. AQP2 was seen in apical cell membranes of the branching ureteric
      bud and CD system from 12 wk and throughout development. In adult normal kidneys,
      AQP1 was localized to apical and basolateral membrane domains of PT and DTL,
      whereas AQP2 was restricted to principal cells of CD. This distribution of AQP1
      and AQP2 was also seen in early stage ADPKD, except that AQP1 was mostly located
      in the apical membrane region of expanded PT. In end-stage ADPKD, two-thirds of
      the cysts expressed either AQP1 or AQP2, but these two water channels were never
      colocalized in the same cyst. Western blot analysis showed maximal expression of
      AQP1 and AQP2 in normal adult kidneys, lower levels in fetal kidneys, and
      decreases associated with degree of cystic progression in ADPKD. These data 1)
      demonstrate specific, mutually exclusive localization of AQP1 and AQP2 in human
      fetal and adult kidneys; 2) show that both channels are expressed early during
      nephrogenesis; and 3) show that the mutual exclusivity of localization is
      maintained even into end-stage ADPKD.

PMID- 8760260
TI  - Pharmacokinetics and renal metabolism of atrial natriuretic factor during rat
      pregnancy.
AB  - The present studies were done to determine if the attenuation of the natriuretic
      and diuretic effects of atrial natriuretic factor (ANF) during rat pregnancy was
      caused by an increase in its metabolism. It was found that the plasma half-life
      (min), plasma clearance (ml.kg-1.min-1), and volume of distribution (ml/kg) of
      ANF were, respectively, 2.5 +/- 4, 115 +/- 19, and 371 +/- 44 in pentobarbital
      anesthetized virgin rats (n = 6) and not different from the corresponding values
      of 3.1 +/- 0.5, 124 +/- 26, and 526 +/- 120 in 20-day gravid animals (n = 6).
      Rates of metabolism of ANF (pmol.min-1.microgram protein-1) by renal cortical
      membranes from virgin (n = 5) and gravid (n = 5) rats were, respectively, 45 +/-
      0.6 and 45 +/- 0.5; likewise, cortical membrane neutral endopeptidase activities
      in virgin and 20-day gravid rats (n = 7) did not differ. It is concluded that the
      attenuation of the renal effects of ANF during pregnancy is not caused by changes
      in its systemic or renal metabolism but might be due to a decrease in guanylate
      cyclase-linked renal ANF receptors and/or receptor-mediated effects.

PMID- 8760261
TI  - Response of hepatic amino acid consumption to chronic metabolic acidosis.
AB  - In a previous paper, we showed that an inhibition of amino acid transport across
      the liver plasma membrane is responsible for the decrease in urea synthesis in
      acute metabolic acidosis. We have now studied the mechanism responsible for the
      decline in urea synthesis in chronic acidosis. Chronic metabolic acidosis and
      alkalosis were induced by feeding three groups of rats HCl, NH4Cl, and NaHCO3 (8
      mmol/day) for 7 days. Amino acids and NH4+ were measured in portal vein, hepatic
      vein, and aortic plasma, and arteriovenous differences were calculated. The rates
      of urinary urea and NH4+ excretion were also determined. Hepatic amino acid
      consumption was lower in both HCl and NH4Cl acidosis compared with NaHCO3-fed
      rats. Glutamine release was not different in the three conditions. Because
      intrahepatic concentrations of amino acids and intracellular protein degradation
      were similar under these conditions, it can be concluded that at low blood pH
      amino acid catabolism may be inhibited and might explain the observed decrease in
      urea excretion in HCl, but not NH4Cl, acidosis; urea excretion was comparable in
      the NH4Cl and NaHCO3 groups presumably because the increased NH4+ load in the
      former group was processed, uninhibited, to urea. Amino acids not used by the
      liver in acidosis could account for the 25-fold increase in NH4+ excretion in HCl
      and NH4Cl compared with alkalosis (P < 0.05). These findings indicate that urea
      synthesis is decreased in chronic HCl acidosis. They show that urea synthesis is
      controlled in chronic, as in acute, acidosis by amino acid uptake by the liver
      and/or intrahepatic degradation and that the ornithine cycle per se has only
      minor control of acid-base homeostasis.

PMID- 8760262
TI  - Expression of the renal 25-hydroxyvitamin D-24-hydroxylase gene: regulation by
      dietary phosphate.
AB  - 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] plays a key role in phosphate (Pi)
      homeostasis through its phosphatemic actions on intestine and bone. In turn,
      dietary Pi restriction increases serum 1,25(OH)2D3 by stimulating its production,
      but its effect on vitamin D catabolism is less clear. Here we have examined the
      effects of dietary Pi on the expression of the renal vitamin D-24-hydroxylase (24
      OHase), the first enzyme in the catabolic pathway for vitamin D compounds. Rats
      fed a low Pi (0.02% P) diet showed a fivefold decrease in renal 24-OHase mRNA
      compared with rats fed a normal Pi (0.67% P) diet. 24-OHase mRNA and 24-OHase
      activity decreased within 24 h of Pi restriction, reached a minimum by 48 h, and
      remained low through 14 days. Decreased 24-OHase mRNA was observed with more
      moderate Pi restriction (0.2% P), but higher Pi (1.2% P) did not increase 24
      OHase mRNA over the 0.8% P diet. 24-OHase mRNA correlated well with plasma Pi (r
      = 0.862, P < 0.001). In conclusion, renal 24-OHase expression is regulated by
      dietary phosphate at the mRNA level.

PMID- 8760263
TI  - Role of reactive oxygen metabolites in DNA damage and cell death in chemical
      hypoxic injury to LLC-PK1 cells.
AB  - Hypoxia is considered to result in a necrotic form of cell injury. We have
      recently demonstrated a role of endonuclease activation, generally considered a
      feature of apoptosis, to be almost entirely responsible for DNA damage in hypoxic
      injury to renal tubular epithelial cells. The role of reactive oxygen metabolites
      in endonuclease-induced DNA damage and cell death in chemical hypoxic injury has
      not been previously examined. LLC-PK1 cells exposed to chemical hypoxia with
      antimycin A resulted in enhanced generation of intracellular reactive oxygen
      species as measured by oxidation of a sensitive fluorescent probe, 2',7'
      dichlorofluorescin diacetate. Superoxide dismutase, a scavenger of superoxide
      radical, significantly reduced the fluorescence induced by antimycin A and
      provided significant protection against chemical hypoxia-induced DNA strand
      breaks (as measured by the alkaline unwinding assay). Pyruvate, a scavenger of
      hydrogen peroxide, provided significant protection against chemical hypoxia
      induced DNA strand breaks and DNA fragmentation (as measured by agarose gel
      electrophoresis). The interaction between superoxide anion and hydrogen peroxide
      in the presence of a metal catalyst leads to generation of other oxidant species
      such as hydroxyl radical. Hydroxyl radical scavengers, dimethylthiourea,
      salicylate, and sodium benzoate, and two metal chelators, deferoxamine and 1,10
      phenanthroline, also provided marked protection against DNA strand breaks and DNA
      fragmentation. These scavengers of reactive oxygen metabolites and metal
      chelators provided significant protection against cell death as measured by
      trypan blue exclusion and lactate dehydrogenase release. Taken together, these
      data indicate that reactive oxygen species play an important role in the
      endonuclease activation and consequent DNA damage, as well as cell death in
      chemical hypoxic injury to renal tubular epithelial cells.

PMID- 8760264
TI  - Metabolic alkalosis decreases bone calcium efflux by suppressing osteoclasts and
      stimulating osteoblasts.
AB  - In vivo and in vitro evidence indicates that metabolic acidosis, which may occur
      prior to complete excretion of end products of metabolism, increases urinary
      calcium excretion. The additional urinary calcium is almost certainly derived
      from bone mineral. Neutralization of this daily acid load, through the provision
      of base, decreases calcium excretion, suggesting that alkali may influence bone
      calcium accretion. To determine whether metabolic alkalosis alters net calcium
      efflux (JCa+) from bone and bone cell function, we cultured neonatal mouse
      calvariae for 48 h in either control medium (pH approximately equal to 7.4, [HCO3
      ] approximately equal to 24), medium simulating mild alkalosis (pH approximately
      equal to 7.5, [HCO3-] approximately equal to 31), or severe alkalosis (pH
      approximately equal to 7.6, [HCO3-] approximately equal to 39) and measured JCa+
      and the release of osteoclastic beta-glucuronidase and osteoblastic collagen
      synthesis. Compared with control, metabolic alkalosis caused a progressive
      decrease in JCa+, which was correlated inversely with initial medium pH (pHi).
      Alkalosis caused a decrease in osteoclastic beta-glucuronidase release, which was
      correlated inversely with pHi and directly with JCa+. Alkalosis also caused an
      increase in osteoblastic collagen synthesis, which was correlated directly with
      pHi and inversely with JCa+. There was a strong inverse correlation between the
      effects alkalosis on osteoclastic beta-glucuronidase release and osteoblastic
      collagen synthesis. Thus metabolic alkalosis decreases JCa+ from bone, at least
      in part, by decreasing osteoclastic resorption and increasing osteoblastic
      formation. These results suggest that the provision of base to neutralize
      endogenous acid production may improve bone mineral accretion.

PMID- 8760265
TI  - Effect of vasopressin on renal lithium reabsorption: a micropuncture and
      microperfusion study.
AB  - Micropuncture techniques were used to investigate the nephron site(s) responsible
      for the vasopressin-induced reductions in lithium clearance and fractional
      lithium excretion (FELi) in anesthetized Brattleboro rats lacking endogenous
      vasopressin. In rats treated intravenously with the vasopressin analogue 1
      desamino-8-D-arginine vasopressin (DDAVP; 40 pg/min), FELi was significantly
      lower than in untreated animals (0.23 +/- 0.01 vs. 0.28 +/- 0.02, P < 0.05). Free
      flow micropuncture showed that fractional lithium delivery (FDLi) to late
      proximal convolutions was identical in the two groups, whereas at the early
      distal tubule both FDLi (0.28 +/- 0.02 vs. 0.33 +/- 0.01, P < 0.05) and the
      tubular fluid-to-plasma lithium concentration ratio (1.18 +/- 0.04 vs. 1.36 +/-
      0.06, P < 0.05) were lower in the DDAVP-treated group. No differences between the
      groups with respect to lithium handling beyond the early distal tubule were
      observed. In rats subjected to in vivo microperfusion of loops of Henle,
      intravenous infusion of DDAVP (40 pg/min) increased fractional lithium
      reabsorption in the loop from 0.56 +/- 0.03 to 0.66 +/- 0.04 (P < 0.05) and from
      0.39 +/- 0.02 to 0.45 +/- 0.02 (P < 0.05) at perfusion rates of 10 and 15 nl/min,
      respectively. We conclude that DDAVP stimulates lithium reabsorption in the loop
      of Henle and suggest that this results from an increased transepithelial
      potential difference in the thick ascending limb.

PMID- 8760266
TI  - Organic osmolyte distribution and levels in the mammalian urinary bladder in
      diuresis and antidiuresis.
AB  - Inositol, sorbitol, glycerophosphocholine (GPC), and betaine are organic
      osmolytes that are accumulated by renal medullary cells in response to
      hyperosmotic stress. Previous screening studies, using nuclear magnetic resonance
      spectroscopy, have shown some of these same compounds to be present in extracts
      of whole urinary bladder from rabbits and rats. In the present study, we used
      high-performance liquid chromatography to quantify levels of these compounds in
      the separated epithelium and muscle of bladders taken from normal rabbits as well
      as diuretic and thirsted rats. We find that 1) high concentrations of organic
      osmolytes, namely inositol, GPC, and sorbitol, are present in urinary bladder; 2)
      levels of these osmolytes in the bladder epithelium are higher than in the
      muscle; 3) increased urinary osmolality due to antidiuresis is associated with a
      2.4-fold increase in total osmolyte levels in rat bladder epithelium and a lesser
      (1.5-fold) increase in the muscle, compared with corresponding levels in tissues
      from diuretic animals; and 4) these increases in total osmolyte amounts in the
      epithelium are due to increased levels of GPC, sorbitol, and perhaps inositol (P
      = 0.07), whereas only GPC increases in the bladder muscle.

PMID- 8760267
TI  - Abnormal renal development in the Os/+ mouse is intrinsic to the kidney.
AB  - The oligosyndactylism (Os/+) mouse, is a genetic model for oligomeganephronic
      congenital renal hypoplasia. To define the abnormality in renal development and
      to determine whether the abnormality is kidney autonomous, we examined kidneys
      from newborn and 21- and 63-day-old Os/+ and wild-type (+/+) mice, obtained
      metanephric kidneys from embryonic day 12 (E12) Os/+ and +/+ embryos, and
      compared growth and development of the metanephroi in vitro. Kidneys from newborn
      Os/+ mice were smaller than those from newborn +/+ mice and contained fewer
      glomeruli per midsagittal section. Following birth, kidneys from Os/+ mice
      manifest compensatory growth of glomeruli and proximal tubules. Metanephroi from
      E12 Os/+ and +/+ embryos were comparable in size. However, during 4 days in
      culture, growth and development of metanephroi from Os/+ embryos were visibly
      reduced compared with metanephroi from +/+ embryos. Expression of B cell
      leukemia/lymphoma gene 2 (bcl-2), the absence of which is known to result in
      congenital renal hypoplasia, was detected in the Os/+ mouse kidneys. We conclude
      that the renal abnormality in Os/+ mice is intrinsic to the kidney and does not
      result from the absence of bcl-2 expression.

PMID- 8760268
TI  - Effect of atrial natriuretic peptide on renal hemodynamics and sodium excretion
      during human pregnancy.
AB  - The effect of infused atrial natriuretic peptide (ANP) on sodium excretion (UNa),
      glomerular filtration rate (GFR), and effective renal plasma flow (ERPF) was
      studied in 12 normotensive primigravidae at 32 wk gestation [late pregnancy (LP)]
      and again 4 mo postpartum [nonpregnant (NP)]. Three 20-min steady-state (renal)
      clearances of inulin and p-aminohippurate were used to measure GFR and ERPF,
      respectively, before and after infusion of ANP at 2 pmol.kg-1.min-1. Basal plasma
      ANP (pANP) was increased in LP compared with NP [7.8 +/- 0.6 vs. 3.3 +/- 0.4
      pmol/l (P < 0.0001), respectively]. In LP, infusion of ANP increased pANP from
      7.8 +/- 0.6 to 21.8 +/- 1.4 pmol/l (P < 0.00001), which produced a natriuresis
      [UNa of 0.18 +/- 0.02 vs. 0.25 +/- 0.03 mmol/min (P = 0.03), respectively], with
      no change in GFR (153 +/- 13 vs. 142 +/- 8 ml/min, P = 0.16) but a significant
      reduction in ERPF (766 +/- 52 vs. 660 +/- 31 ml/min, P = 0.002). In NP, ANP
      infusion increased pANP from 3.3 +/- 0.4 to 27.7 +/- 2.5 pmol/l (P < 0.00001),
      which produced no significant natriuresis [UNa of 0.22 +/- 0.07 vs. 0.26 +/- 0.09
      mmol/min (P = 0.15), respectively] and no change in GFR (87 +/- 3 vs. 89 +/- 3
      ml/min), but again a reduction in ERPF (486 +/- 17 vs. 414 +/- 9 ml/min, P <
      0.001).

PMID- 8760269
TI  - Characteristics of human antibody repertoires following active immune responses
      in vivo.
AB  - Possibilities to develop human monoclonal antibody specificities have recently
      been much facilitated by improvements of human hybridoma technology but even more
      so by the emerging phage-display technique. However, until recently very little
      has been known about the characteristics at the molecular level of the induced, T
      cell-dependent human antibody response, frequently targeted by these techniques.
      Rather, the major part of available sequence information has been related to
      tumor-derived or autoreactive antibodies. We have now investigated high affinity,
      monospecific, human antibody repertoires as developed by hybridoma technology.
      The VH region gene usage among such in vivo-induced repertoires is in only some
      respects similar to that found in the total B cell population. A limited number
      of heavy-chain variable segment loci account for the majority of all induced
      antibodies. A particular VH gene locus (4-34) frequently employed by peripheral B
      cells and associated with autoreactive antibodies was rarely used by the induced
      repertoire. Furthermore, in particular antigen systems, V region usage differs
      from the total available repertoire, and heavy-chain CDR3 is generally longer
      among antibodies induced against foreign protein antigens than in the average B
      cell population. Light-chain gene usage is often restricted to just a few
      dominant genes frequently found among B cells in general. In comparison, variable
      regions derived by phage-display technology in some antigen systems display even
      longer heavy-chain CDR3 than hybridoma-derived antibodies. This technique also
      appears to select a different set of germline genes preferentially (both with
      respect to VH and JH) as compared to hybridoma technology. In summary, the T cell
      dependent antibody response against foreign antigens appears to differ from the
      average circulating B cell in several ways, and thus does not seem to represent a
      random selection of the available repertoire.

PMID- 8760270
TI  - Low level formation of potent catalytic IgG fragments mediated by disulfide bond
      instability.
AB  - A highly purified preparation of a monoclonal antibody to vasoactive intestinal
      peptide (VIP) was analysed by gel filtration. Three peaks of VIP hydrolysing
      activity were observed, corresponding to the 150 kDa tetramer IgG, 80 kDa dimer
      of the heavy and light chains (H-L dimer) and 25 kDa L chain monomer. The
      hydrolytic activity of all three peaks was removed by adsorption on immobilized
      anti-mouse IgG. The specific activities (CPM hydrolysed/microgram protein) of the
      H-L dimer and the L chain monomer were more than 30-fold greater than of intact
      IgG. The presence of small amounts of the antibody fragments in unreduced IgG
      preparations was confirmed by electrophoresis of overloaded radiolabeled and
      unlabeled IgG preparations. Increased levels of the fragments were evident after
      prolonged incubation of a dilute solution of 125I-IgG at 37 degrees C.
      Iodoacetamide, a sulfhydryl alkylating reagent, suppressed the production of IgG
      fragments. Incubation of 125I-labeled L chain with unlabeled IgG resulted in
      incorporation of small amounts of the radioactivity into disulfide bonded 150 kDa
      IgG tetramer and 50 kDa L chain dimer fractions. These observations implicate
      disulfide reduction and exchange reactions as the mechanism underlying formation
      of the IgG fragments. Like the antibody fragments found in unreduced IgG, the L
      chain monomer and non-covalently associated H-L dimer isolated from reduced and
      alkylated IgG were capable of hydrolysing VIP. Hydrolysis of VIP by the
      recombinant L chain subunit was inhibited by excess IgG, suggesting that high
      affinity VIP binding by IgG limits its hydrolysis by the L chain. These
      observations suggest that small amounts of high activity antibody fragments may
      contribute to the catalytic characteristics of the anti-VIP IgG preparation.

PMID- 8760271
TI  - Metal-binding properties of a calcium-dependent monoclonal antibody.
AB  - The calcium-dependent mAb, M1 (also called anti-Flag or 4E11) was studied using a
      newly developed metal-sensitive enzyme-linked immunosorbent assay (ELISA). This
      antibody, specific for a calcium complex of the peptide antigen, Asp-Tyr-Lys-Asp
      Asp-Asp-Asp-Lys, has found widespread use as a mild purification reagent for Flag
      epitope tagged recombinant proteins. Although M1 affinity columns release
      monovalent Flagged proteins in the absence of calcium, the antibody retains
      substantial affinity for the Flag sequence even in metal-free conditions, so that
      it has been impossible to use it to develop a metal-sensitive ELISA assay. This
      is due to the ability of the antibody to remain bound to polyvalent surface
      coated antigen, for instance, when Flagged proteins are bound to ELISA plates or
      blotting filters. The resultant antigen polyvalence raises the avidity of the
      Flag antibody to a point where the reaction is essentially calcium-independent.
      However, when the antibody itself was made monovalent, by proteolytic cleavage to
      the Fab, this situation was reversed and the ELISA reaction became calcium
      dependent. This new metal-dependent ELISA assay was used to explore the metal
      requirements of the antibody in detail. Among divalent metals, binding tapered
      off with increasing radius above that of calcium, or with decreasing radius below
      that of calcium. Several smaller metals, such as nickel, acted as inhibitors of
      the binding reaction. Substantial binding was demonstrated for heavy metals such
      as cadmium, lanthanum and samarium. Because it is of interest to use this
      antibody for the co-crystallization of recombinant Flag-fusion proteins, the
      ability to bind heavy metals was a significant finding.

PMID- 8760272
TI  - Immunological effect of a synthetic growth hormone peptide on the growth
      performance in swine.
AB  - A mouse monoclonal antibody (mAb), designated PS-7.6, was previously shown to
      enhance the activity of porcine growth hormone (pGH) in promoting the growth of
      hypophysectomized (hypox) rats. Epitope mapping studies indicated that the region
      recognized by PS-7.6 resided within an amino acid sequence 54-95 of pGH. A
      peptide corresponding to this sequence was synthesized and found to induce swine
      antibodies capable of augmenting pGH activity in hypox rats. On the basis of
      these previous observations, an attempt was made in this study to determine
      whether or not the peptide pGH(54-95) could be used as a vaccine to elicit
      antibodies functionally similar to PS-7.6 mAb, thus potentiating the efficacy of
      endogenous GH in swine. Young pigs (15-20 kg) were immunized with pGH(54-95) that
      had been conjugated with ovalbumin (OVA) and boosted twice at 4-week intervals.
      Control animals were similarly immunized with OVA. The weight gains and feed
      consumption of these animals were closely monitored throughout the trials. A
      number of carcass parameters were also examined when these animals reached 110
      120 kg, at which time they were killed. Results indicated that immunization with
      peptide significantly accelerated the daily weight gain during the growing phase
      of growth. However, this effect disappeared during the finishing phase of growth.
      The failure to prolong the initial growth effect by the peptide immunization
      apparently correlated with the kinetics of antibody production, because
      antibodies immunoreactive to the peptide and pGH were detected in these animals
      after immunization but gradually diminished. This idea was supported by the fact
      that antibodies obtained from pigs 5 and 9 weeks after the initial immunization
      potentiated the activity of pGH in hypox rats, whereas antibodies harvested at
      week 16 did not. Furthermore, carcass evaluation was performed at time of killing
      and showed that the leaf fat and loin eye muscle were also significantly improved
      by peptide immunization. Taken together, the present findings suggest that pGH(54
      95) peptide can be employed as a potential growth-promoting vaccine to improve
      the performance of swine.

PMID- 8760273
TI  - Characterization, application and potential uses of biotin-tagged inhibitors for
      lymphocyte serine proteases (granzymes).
AB  - Cytotoxic lymphocytes and natural killer cells are able to kill their target
      cells in minutes. The death of the target cell occurs after the release of
      cytoplasmic granules from the effector cell. These granules contain the pore
      forming protein perforin and serine proteases (granzymes). To date 10 genes
      encoding lymphocyte granzymes have been discovered; of these only four have been
      purified and characterized for their substrate specificity. Several are predicted
      to have a common chymase, like specificity which is found in the granule
      extracts. Others may need to be enriched as active enzymes before they can be
      evaluated for substrate hydrolysis. Due to the limitations of detection by
      substrate hydrolysis, a more sensitive method for the detection of dilute
      granules was needed. We report the differing reactivities of seven biotin (Bi)
      tagged isocoumarin (IC) inhibitors for Asp-ase, chymase, tryptase and Met-ase
      granzymes. The inhibitors contained different substituents at their no. 3
      position: methoxy (OMe), ethoxy (OEt), propoxy (OPr) or 2-phenylethoxy (OEtPh)
      groups. The OMe group conferred general reactivity, whereas the OEtPh group
      conferred selective reactivity with chymase granzymes. The inhibitors that
      contained the longest aminocaproyl (Aca) spacers between the biotin-tag and the
      isocoumarin ring mediated the most stable granzyme inactivation. These inhibitors
      were the most effective at blocking lysis of red blood cells by the granule
      extracts. The inhibitors were used in protein blotting experiments where the
      biotin was detected with an avidin-enzyme complex. Over 10 granzymes were
      labelled by the inhibitor Bi-Aca-Aca-IC-OMe. The inhibitors detected granzymes
      when they were not readily detected by substrate hydrolysis.

PMID- 8760274
TI  - Immune responses to self peptides naturally presented by murine class II major
      histocompatibility complex molecules.
AB  - Peptides eluted from murine Major Histocompatibility Complex (MHC) class II
      molecules are predominantly fragments of self proteins, which include
      apolipoprotein E, cystatin-c, transferrin receptor, MHC class II and Ii chains.
      These naturally processed self peptides are expected to be presented during
      ontogeny. Therefore, immune responses to these peptides in syngeneic hosts may be
      under physiological control so as to modulate auto-reactivity. As would be
      expected from our current understanding, T cells reactive to such antigens should
      be deleted or clonally anergized. To explore this possibility, we investigated
      the immunogenicity of a number of these self peptides in mice that express MHC
      class II, from which these peptides were eluted. T cell and antibody responses
      were measured following immunization of mice with the appropriate peptide.
      Surprisingly, many of these peptides were highly immunogenic in normal mice. T
      cells reactive to these self peptides are restricted by syngeneic MHC class II
      and were blocked by alpha CD4 antibodies. T cells primed with the native protein
      in vivo could be challenged with the appropriate self peptide in vitro. Some of
      the self epitopes induce Th1 cells as indicated by IFN-gamma but not IL-4
      production and others induce Th2 cells. Antipeptide antibodies were detected only
      at higher doses of antigen. Our results suggest that T cells specific for many of
      the naturally processed self peptides are not deleted but tolerance to these
      peptides is still maintained in vivo. Presumably the high-affinity self-reactive
      T cells are deleted in the thymus and the low-affinity self peptide reactive T
      cells remain unresponsive to antigen challenge in vitro. Upon antigen priming in
      vivo, many of these self-reactive T cells become activated and readily respond to
      antigen challenge in vitro. These results point to the physiological control of
      the maintenance of tolerance to naturally processed self peptides.

PMID- 8760275
TI  - Binding of cynomolgus monkey IgE to a humanized anti-human IgE antibody and human
      high affinity IgE receptor.
AB  - Antibodies which block IgE binding to its high affinity receptor have the
      therapeutic potential for treating allergic diseases. A humanized anti-human IgE
      antibody (E25) was developed for this purpose. Cynomolgus monkeys were used for
      preclinical studies of E25. We studied the binding of purified human IgE and
      cynomolgus monkey IgE to E25 and the human high affinity IgE receptor alpha-chain
      IgG fusion molecule (Fc epsilon RI-IgG) by surface plasmon resonance. Human IgE
      and cynomolgus monkey IgE bound to immobilized E25 with similar affinity
      (apparent Kd = 0.06 and 0.19 nM, respectively). Human IgE and cynomolgus monkey
      IgE also bound to immobilized Fc epsilon RI-IgG with similar affinity (apparent
      Kd = 0.28 and 0.30 nM, respectively). These data suggest that the cynomolgus
      monkey is a valid model for preclinical studies of the E25 antibody and probably
      for other antibodies which block IgE binding to its receptor. An enzyme-linked
      immunosorbent assay (ELISA) for measuring cynomolgus monkey IgE was developed to
      support preclinical studies. This ELISA used FcERI-IgG for capture and peroxidase
      labelled goat polyclonal antibody to human IgE for detection. Using purified
      cynomolgus monkey IgE as the standard, the serum IgE levels in six cynomolgus
      monkeys measured were 4-23 micrograms/ml.

PMID- 8760276
TI  - Sulfonated dextran inhibits complement activation and complement-dependent
      cytotoxicity in an in vitro model of hyperacute xenograft rejection.
AB  - In the present study, we demonstrate that a substituted soluble dextran
      derivative bearing 73% carboxylic groups and 15% benzylamide sulfonate groups,
      termed CMDBS25, inhibits complement activation and complement-mediated damage in
      an in vitro model of xenogeneic rejection. Incubation of porcine aortic
      endothelial cells with normal human serum resulted in time-dependent complement
      consumption as assessed by C3a generation in the fluid phase and deposition of
      activated complement fragments C3, C5 and of C5b-9 on target cells. The presence
      of C5b-9 membrane attack complex was associated with 51Cr release from
      prelabelled endothelial cells. The addition of 5-25 mg of CMDBS25/ml under the
      experimental conditions used, inhibited complement activation and C3a generation
      in a dose-dependent fashion. CMDBS25 (25 mg/ml) totally suppressed iC3b, C5 and
      C5b-9 cytolytic complex deposition on cells and inhibits by 42% lysis of target
      endothelial cells. Native dextran had no effect. Our observations document the
      anti-complementary properties of sulfonated dextran derivatives and their
      potential as therapeutic agents for the prevention of complement-dependent
      hyperacute xenograft rejection.

PMID- 8760278
TI  - Analysis of the interaction between a synthetic peptide of influenza virus
      hemagglutinin and monoclonal antibodies using an optical biosensor.
AB  - The interaction between two monoclonal antibodies and their corresponding Fab'
      fragments with a synthetic peptide, corresponding to the C-terminal 23 residues
      of the HA1 chain of influenza virus hemagglutinin against which they were
      generated, has been examined using an optical biosensor employing the detection
      principal of surface plasmon resonance (Pharmacia BIAcore). The data obtained has
      been analysed in detail by linear transformation of the primary data and
      nonlinear regression analysis, as well as by analysis of equilibrium binding
      data. The 2/1 antibodies and their Fab' fragments displayed higher affinity than
      the corresponding 1/1 proteins. The IgGs were found to have equilibrium
      association constants (KA) 10-20-fold higher than the corresponding Fab'
      fragments. This appears largely to be due to differences in the dissociation rate
      constant (kd) and probably reflects increased avidity due to bivalent binding.

PMID- 8760277
TI  - Generation and characterization of a human monoclonal autoantibody that acts as a
      high affinity interleukin-1 alpha specific inhibitor.
AB  - Interleukin-1 (IL-1) defines two polypeptides, IL-1 alpha and IL-1 beta, that
      possess a wide spectrum of biological effects. Two natural antagonists of IL-1
      action have been characterized: the IL-1 receptor antagonist (IL-1Ra) and a
      soluble form of the type II IL-1 receptor. Neutralizing autoantibodies to IL-1
      alpha have also been detected in sera of healthy individuals and patients with
      autoimmune or inflammatory diseases. To characterize such antibodies molecularly,
      we attempted to generate B cell clones producing anti-IL-1 alpha human monoclonal
      antibody (HuMAb) by combining Epstein-Barr virus-immortalization and CD40
      activation of B lymphocytes from individuals with circulating anti-IL-1 alpha. We
      describe herein the generation and properties of a natural IgG4/kappa anti-IL-1
      alpha monoclonal autoantibody, HuMAb X3, that bound specifically to human IL-1
      alpha, but not to IL-1 beta and IL-1Ra, with a high affinity (Kd = 1.2 x 10(
      10)M). HuMAb X3 inhibited IL-1 alpha binding to IL-1 receptors and neutralized
      biological activities of both recombinant and natural forms of IL-1 alpha. A
      recombinant form of HuMAb X3 was found to display identical specific IL-1 alpha
      antagonism. The presence of somatic mutations within X3 variable regions suggests
      an antigen-driven affinity maturation. This study extends the demonstration of
      the presence of high affinity neutralizing anti-IL-1 alpha autoantibodies that
      can function as a third type of IL-1 antagonist.

PMID- 8760279
TI  - Tumor necrosis factor-alpha (TNF-alpha) induces a reversible, time- and dose
      dependent adhesion of progenitor T cells to endothelial cells.
AB  - Recent in vivo studies suggest that tumor necrosis factor-alpha (TNF-alpha) is
      involved in the development of the thymus. We postulated that this inflammatory
      mediator could regulate the influx of progenitor T cells into the thymus. Using
      an in vitro static adhesion system, we found that TNF-alpha increases the
      adhesion of a murine progenitor T cell line (FTF1) to a bovine aortic endothelial
      cell line (1F8), human umbilical vein endothelial (HUVE) cells, and a murine
      arterial endothelial (MAE) cell line. TNF-alpha treatment of the 1F8 cells
      resulted in a time- and dose-dependent increase in the adherence of FTF1 cells.
      Adherence increased during the first 6 hr of treatment with TNF-alpha
      concentrations ranging from 10(-11) to 10(-9) M. Maximal adherence (6 hr
      treatment with 10(-10) M of TNF-alpha) was approximately 4.5-fold larger than
      that of untreated monolayers. A slow decrease in adherence, down to approximately
      2-fold at 48 hr, was observed beyond 12 hr of TNF-alpha treatment; in contrast,
      removal of TNF-alpha after 6 hr of continued stimulation caused the adherence to
      return to pre-stimulation levels within 24-30 hr. Adhesion of FTF1 cells to TNF
      alpha treated 1F8 cells was almost completely blocked by a monoclonal antibody
      against murine CD49d (very late antigen-4) expressed on FTF1 cells. TNF-alpha
      induced adhesion of FTF1 cells to MAE cells was also blocked by monoclonal
      antibodies against murine CD49d and CD106 (vascular cell adhesion molecule-1).
      These results support the notion that local secretion of TNF-alpha could modulate
      the dynamics of adhesion of progenitor T cells to the thymic endothelium.

PMID- 8760280
TI  - Protection against alpha-bungarotoxin poisoning by immunization with synthetic
      toxin peptides.
AB  - The purpose of the present work was to determine the ability of BgTX peptides,
      corresponding to the various loops and exposed regions of alpha-bungarotoxin
      (BgTX) and representing regions that are recognized by B and/or T cells, to
      stimulate protective immunity in mice against in vivo challenge with BgTX. The
      BgTX LD50 values in non-immune mice or mice that had been immunized with proteins
      and peptides unrelated to BgTX were: Balb/c, 0.128 microgram/g; SJL, 0.156
      microgram/g. Immunization of Balb/c and SJL mice with each of the synthetic
      peptides in its free form afforded considerable protection against BgTX
      poisoning. Peptides L1 (residues 3-16), L2 (residues 26-41) and C-tail (residues
      66-74) of BgTX were the most protective and mice immunized with these peptides
      survived LD50 values that were three times higher than control mice. Immunization
      with an equimolar mixture of the three peptides was even more protective and
      these mice survived even higher challenge doses of BgTX (4.6-fold higher than
      LD50 of controls; i.e. protection index, PI = 4.6). An OVA conjugate carrying all
      three peptides, when used as an immunogen, conferred extremely high protection
      (PI > or = 18.1) which was almost double the protection obtained by BgTX
      immunization (PI = 9.7). Thus, the conjugate of the three peptides should serve
      as an effective vaccine against BgTX poisoning. Furthermore, these results with
      BgTX peptides should serve as a prototype for the design and synthesis of peptide
      vaccines against other members of this large family of toxins which include both
      long and short neurotoxins as well as cytotoxins.

PMID- 8760282
TI  - Identification of a murine CD4+ T-lymphocyte response site in hepatitis C virus
      core protein.
AB  - The T cell response to a recombinant HCV truncated core protein (cp1-10) was
      measured in a proliferation assay. Based on a 10-fold greater response to this
      truncated core protein than to its shorter form (cp1-8), a predominant epitope
      was mapped to the carboxyl quarter of this sequence. This epitope was further
      mapped to a synthetic peptide corresponding to amino acids 121-140 of the core
      protein. The peptide was antigenic for T cells of all three H-2 types tested, H-2
      r, b and d, and the proliferating T cells were CD4+. Besides inducing specific
      proliferation in vitro, peptide aa121-140 can prime helper T cells in vivo. When
      boosted with core protein, mice primed with peptide produced 64-fold higher
      antibody titer than without priming in 1 week. The identification of a broadly
      immunogenic T cell helper epitope on core protein may be important for vaccine
      design against HCV.

PMID- 8760281
TI  - Changes in abundance of IgG 2a mRNA in the nucleus and cytoplasm of a murine B
      lymphoma before and after fusion to a myeloma cell.
AB  - Changes in IgG mRNA half-life, transcription and nuclear and cytoplasmic
      abundance were studied in two cell lines which contain an identical Ig gamma 2a
      heavy chain but which differ in its expression. The A20.2J mouse lymphoma
      expresses about equal amounts of Ig gamma 2a secretory- and membrane-specific
      mRNAs whereas in the AXJ hybrids, resulting from the fusion of A20.2J with the
      J558L myeloma, the secretory-specific form dominates. Further evidence of
      dominance of the myeloma phenotype was seen in the large changes in mRNA
      abundance and nuclear accumulation as well as in a small increase in Ig gamma 2a
      mRNA half-lives for both secretory and membrane forms. Contributing to the
      observed > 100-fold increase in the ratio of secretory vs membrane forms of the
      Ig gamma 2a heavy chain in the AXJ hybrids are both a 10-fold decrease in the
      production of the membrane form by post-transcriptional RNA processing events and
      a approximately 6-7-fold decrease in the nuclear to cytoplasmic ratio for the Ig
      secretory gamma 2a and kappa light chain RNAs. Differential RNA accumulation in
      the nucleus in the lymphoma cell therefore contributes to the differential
      expression of Ig secretory mRNA.

PMID- 8760283
TI  - Antibody networks and imaging: elicitation of anti-fluorescein antibodies in
      response to the metatypic state of fluorescein-specific monoclonal antibodies.
AB  - Studies are described regarding generation of anti-hapten antibodies starting
      with a monoclonal Ig immunogen in the ligand-induced conformation or metatypic
      state. Liganded monoclonal Ab1 antibodies represent the unique feature of the
      study since previous reports investigating internal imaging in the original
      Idiotype Network Hypothesis [Jerne, 1974 (Ann. Immun. 125C, 373-389)] were based
      on the non-liganded or idiotypic state [as reviewed in: Rodkey, 1980 (Microbiol.
      Rev. 44, 631-659); Kohler et al., 1979 (In: Methods in Enzymology: Antibodies,
      Antigens and Molecular Mimicry, pp. 3-35); Greenspan and Bona, 1993 (FASEB J.
      7,437-444)]. Affinity-labeled liganded murine monoclonal anti-fluorescein
      antibodies served as immunogens administered both in the syngenic and xenogenic
      modes to determine if the metatypic state elicited anti-hapten antibodies through
      imaging-like mechanisms. Polyclonal and monoclonal anti-Ab1 reagents in various
      hosts were assayed for anti-fluorescein and/or anti-metatype specificity.
      Significant anti-fluorescein responses were measured indicating that the
      metatypic state directly or indirectly stimulates an anti-hapten antibody
      population.

PMID- 8760284
TI  - Horse complement protein C9: primary structure and cytotoxic activity.
AB  - Lack of hemolytic activity of horse serum is an inherent property of horse C9. To
      understand the molecular reasons for this deficiency we have cloned C9 cDNA from
      a horse liver cDNA library and have sequenced the cDNA yielding the complete
      coding sequence for horse C9. Purification of C9 from horse plasma and
      microsequencing established the N-terminus of the mature protein and verified
      that the correct horse C9 cDNA clone had been isolated. The deduced amino acid
      sequence corresponds to a mature protein of 526 amino acids that is 77% identical
      to human C9. It has the same domain structure as human C9 and contains 22
      cysteines and four invariant tryptophans. The few differences include the N
      terminus, which is an unblocked glycine in horse C9 but pyroglutamine in human
      C9, and three potential N-glycosylation sites compared to two in human C9. The N
      terminal difference is unimportant since microsequencing of bovine C9, which is
      strongly hemolytic, established that it also has an unblocked glycine identical
      to horse C9. There are no obvious structural differences apparent that could
      resolve the differences in hemolytic potency between the two molecules. Aside
      from a few conservative replacements, both C9 sequences are identical between
      positions 250 and 360. This region includes the membrane interaction domain in C9
      and the postulated transmembrane segment that is thought to constitute the wall
      of a putative transmembrane pore and, therefore, should be required for
      cytotoxicity. In agreement with this prediction we have observed that, in
      contrast to the marked decrease in hemolytic activity, horse C9 is very efficient
      in killing a variety of Gram-negative bacteria. These results demonstrate that
      horse C9 is a structurally competent molecule with efficient cytotoxic activity.
      Its inability to lyse erythrocytes may be related to the action of control
      proteins on target cell membranes.

PMID- 8760285
TI  - The paired-box transcription factor, PAX2, positively modulates expression of the
      Wilms' tumor suppressor gene (WT1).
AB  - The Wilms' tumor suppressor gene, wt1, encodes a zinc finger protein which
      functions as a transcriptional regulator. Expression of the wt1 gene is
      developmentally regulated and restricted to a small set of tissues which include
      the fetal urogenital system, mesothelium, and spleen. In the developing kidney,
      induction of neprohogenesis by the ureter is accompanied by an increase in
      expression levels of the Pax-2 gene, a developmentally and spatially regulated
      paired-box member. This is followed by an increase in wt1 expression as
      mesenchymal cells condense and differentiate. In this report, we demonstrate that
      PAX2 isoforms are capable of transactivating the wt1 promoter. Deletion
      mutagenesis of the wt1 promoter identified an element responsible for mediating
      PAX2 responsiveness, located between nucleotides -33 and -71 relative to the
      first wt1 transcription start site. Consistent with its identity as a PAX
      responsive element, multimerization of this mofit upstream of a heterologous
      minimal promoter enhanced reporter activity when co-transfected with a Pax-2
      expression vector. Finally, we demonstrate that PAX2 can stimulate expression of
      the endogenous wt1 gene. These results suggest that a role for PAX2 during
      mesenchyme-to-epithelium transition in renal development is to induce wt1
      expression.

PMID- 8760286
TI  - Rac-1 dependent stimulation of the JNK/SAPK signaling pathway by Vav.
AB  - The protein product of the human vav oncogene, Vav exhibits a number of
      structural motifs suggestive of a role in signal transduction pathways, including
      a leucine-rich region, a plekstrin homology (PH) domain, a cysteine-rich domain,
      two SH3 regions, an SH2 domain, and a central Dbl homology (DH) domain. However,
      the transforming pathway(s) activated by Vav has not yet been elucidated.
      Interestingly, DH domains are frequently found in guanine nucleotide-exchange
      factors for small GTP-binding proteins of the Ras and Rho families, and it has
      been recently shown that, whereas Ras controls the activation of mitogen
      activated kinases (MAPKs), two members of the Rho family of small GTPases, Rac 1
      and Cdc42, regulate activity of stress activated protein kinases (SAPKs), also
      termed c-jun N-terminal kinases (JNKs). The structural similarity between Vav and
      other guanine nucleotide exchange factors for small GTP-binding proteins,
      together with the recent identification of biochemical routes specific for
      members of the Ras and Rho family of GTPases, prompted us to explore whether MAPK
      or JNK are downstream components of the Vav signaling pathways. Using the COS-7
      cell transient expression system, we have found that neither Vav nor the product
      of the vav proto-oncogene, proto-Vav, can enhance the enzymatic activity of a
      coexpressed, epitope tagged MAPK. On the other hand, we have observed that,
      whereas proto-Vav can slightly elevate JNK/SAPK activity, oncogenic Vav potently
      activates JNK/SAPK to an extent comparable to that elicited by two guanine
      nucleotide exchange factors for Rho family members, Dbl and Ost. We also show
      that point mutations in conserved residues within the cysteine rich and DH
      domains of Vav both prevent its ability to activate JNK/SAPK and render Vav
      oncogenically inactive. In addition, we found that coexpression of the Rac-1 N17
      dominant inhibitory mutant dramatically diminishes JNK/SAPK stimulation by Vav,
      as well as reduces the focus-forming ability of Vav in NIH3T3 murine fibroblasts.
      Taken together, these findings provide the first evidence that Rac-1 and JNK are
      integral components of the Vav signaling pathway.

PMID- 8760287
TI  - c-Myc induces apoptosis and cell cycle progression by separable, yet overlapping,
      pathways.
AB  - Enforced c-Myc expression promotes inappropriate cell cycle progression of growth
      factor deprived cells and triggers concomitant apoptosis. However, it is not
      clear what role dysregulation of the cell cycle plays in c-Myc-induced apoptosis.
      Ornithine decarboxylase (ODC) is a transcriptional target of c-Myc and
      contributes to c-Myc induced apoptosis. Here we have established that high levels
      of ODC overexpression in interleukin-3 (IL-3)-dependent 32D.3 myeloid cells
      induces apoptosis at rates comparable to those induced by enforced c-Myc
      expression. However, ODC-induced apoptosis was not accompanied by dysregulation
      of cell cycle controls, indicating that cell death was not triggered by
      inappropriate cell cycle progression. Nonetheless, ODC was required downstream of
      c-Myc for myeloid cell growth. These results suggested that c-Myc-induced
      pathways leading to cell cycle progression and apoptosis are separable, yet that
      they share common mediators. In agreement with this concept, treatment of cells
      over-expressing c-Myc with the growth inhibitory agent dibutyryl cyclic AMP
      (Bt2cAMP) arrested these cells G1, without inducing apoptosis. However, c-Myc
      retained the ability to induce apoptosis of Bt2cAMP-arrested cells following
      removal of IL-3, demonstrating that Bt2cAMP selectively inhibits c-Myc-induced
      pathways promoting cell cycle progression but not apoptosis. These results
      suggest a "multiple effectors' model in which c-Myc regulates the expression of
      mediators which alone are sufficient to induce apoptosis in the absence of
      survival factors, yet are required in concert to promote cell cycle progression.

PMID- 8760288
TI  - HPV-18 E6 inhibits p53 DNA binding activity regardless of the oligomeric state of
      p53 or the exact p53 recognition sequence.
AB  - The E6 proteins of the oncogenic-associated human papillomavirus types 16 (HPV
      16) and 18 (HPV-18) function by interfering with the normal cell cycle control
      mechanisms, particularly those controlled by p53. HPV E6 is able to interfere
      with p53 function by preventing its binding to DNA target sequences and also by
      labelling p53 for ubiquitin-mediated degradation. We have previously reported
      that certain p53 mutants, defective in oligomerisation, vary in their
      susceptibility to E6-directed labelling for ubiquitin-mediated degradation. In
      this paper we report that the strength of p53's binding to DNA is dependent upon
      the precise target sequence, but that E6 is able to disrupt each complex. We also
      report the binding of different oligomeric forms of p53 to different DNA
      sequences and correlate this with in vivo transcriptional activity and
      demonstrate the susceptibility of that DNA binding to disruption by E6. Finally
      we show that the ability of p53 to bind to TBP is a function of its oligomeric
      state and correlates in part with its ability to transrepress but not with its
      ability to transactivate.

PMID- 8760289
TI  - Transcriptional regulation of the human CD9 gene: characterization of the 5'
      flanking region.
AB  - The CD9 antigen, initially discovered on B lineage leukemic cells, belongs to the
      tetraspan superfamily of surface molecules. If no precise function has been
      assigned to any of these molecules, there are some indications that they could be
      involved in cell adhesion and cell migration, as well as malignant progression.
      The CD9 antigen is associated with surface proteins such as VLA integrins or HB
      EGF precursor. Transfection of CD9 in melanoma cells reduces tumor growth and
      metastasis. The heterogenous distribution of the CD9 antigen suggests a complex
      regulation of its expression. We have previously characterized the CD9 gene and
      shown that transcription could be initiated at several sites in the TATA-less 5'
      flanking region. We show here, using as a model two human leukemic cell lines
      with erythromegakaryocytic potential, HEL and K562, that the [-205, -154] region
      supports a promoter activity when cloned ahead of a CAT reporter gene.
      Mutagenesis analysis suggested the presence of a positive element located within
      the [-170, -154] region. Gel shift experiments using HEL extracts were compatible
      with the binding of the transcriptional factor Sp1 to the [-237, -205] region and
      indicated that a non-identified protein binds to the 3' end of the [-205, -154]
      region.

PMID- 8760291
TI  - Isolation from a multigene family of the active human gene of the metastasis
      associated multifunctional protein 37LRP/p40 at chromosome 3p21.3.
AB  - The 37 kD precursor of the 67 kD laminin receptor (37LRP) is a polypeptide whose
      expression is consistently upregulated in aggressive carcinoma. Interestingly,
      the 37LRP appears to be a multifunctional protein involved in the translational
      machinery and has also been identified as p40 ribosome-associated protein.
      Although highly conserved cDNAs corresponding to this polypeptide have been
      isolated from several species including vertebrates, invertebrates, plants and
      prokaryotes, characterization of any of the corresponding active genes has never
      been reported. In this study, we have cloned an intron-containing fragment which
      permitted us to isolate the active 37LRP/p40 human gene. This gene contains seven
      exons and six introns. Ribonuclease protection experiments suggest multiple
      transcription start sites. The promoter area does not bear a TATA box but
      contains four Sp1 sites. The first intron is also GC rich containing five Sp1
      sites. Intron 4 contains the full sequence of the small nuclear RNA E2 and two
      Alu sequences are found in intron 3. Fluorescent in situ hybridization localized
      the 37LRP/p40 active gene on chromosome 3 in the locus 3p21.3 which,
      interestingly, is a hot spot for genetic alterations in several cancers and
      particularly in small cell lung carcinoma.

PMID- 8760290
TI  - Expression of human immunodeficiency virus type I tat results in down-regulation
      of bcl-2 and induction of apoptosis in hematopoietic cells.
AB  - Infection by human immunodeficiency virus type 1 (HIV-1) is characterized by
      progressive loss of various cell types, mainly CD4+ T lymphocytes. While a
      passive role for the virus in cell destruction is recognized, it does not account
      for the vast amount of cell death including those of uninfected "bystander'
      cells. Since in the past we and others have demonstrated the capacity of the Tat
      protein of HIV-1 to modulate the expression of various cellular genes and that
      Tat secreted by HIV-infected cells can be readily taken up by various cell types,
      we have investigated the role of Tat on inducing apoptosis. Our results indicate
      that T lymphocytes transfected to constitutively express HIV-1 tat, when grown
      under serum-free conditions results in rapid apoptosis characterized by typical
      ultrastructural features and DNA fragmentation. Additionally, we observed that in
      several hematopoietic cell types, including T and B lymphoid cells and monocytoid
      cells, the expression of HIV-1 tat results in down-regulation of bcl-2, an
      oncogene with known potential for inhibition of apoptosis. The tat-mediated down
      regulation of bcl-2 was observed at both the transcriptional and translational
      levels. Also, tat-transfected cells expressed increased amounts of bax, a bcl-2
      family protein known to induce apoptosis. While these results support reports in
      the literature of an active role for tat in inducing cell death in HIV-infected
      individuals, they point to a new mechanism involving Tat-mediated modulation of
      bcl-2 and bax.

PMID- 8760292
TI  - Aberrant translational control of the c-myc gene in multiple myeloma.
AB  - We demonstrate a 10- to 25-fold increase in the amount of c-myc protein in
      several independent cell lines derived from patients with multiple myeloma (MM).
      This is not accompanied by a corresponding increase in the overall level of the c
      myc mRNA. There is, however, a 3.4-fold increase in the amount of c-myc mRNA
      associated with the polysomes in these cell lines without any detectable change
      in either the polysome size or the rate of translation elongation, thus
      suggesting that there is an increase in the extent of mobilisation of c-myc mRNA
      to the polysomes in MM. Analysis of the 5' untranslated region of c-myc has
      revealed the presence of a mutation, in all of the MM cell lines examined, in a
      region which has been implicated previously in the translational control of this
      mRNA species. These data suggest aberrant translational control of the c-myc gene
      in cell lines derived from patients with MM, which may contribute towards
      pathogenesis of the disease.

PMID- 8760293
TI  - Platelet-activating factor (PAF) induces the early tyrosine phosphorylation of
      focal adhesion kinase (p125FAK) in human endothelial cells.
AB  - Platelet-activating factor (PAF) is a potent activator of angiogenesis and
      controls the motility and the shape of vascular endothelium. The mechanism(s)
      whereby PAF exerts its action are in part known. Here we report that the
      biological active (R)PAF enantiomer administrated to cultured endothelial cells
      induces the early phosphorylation in tyrosine residues of focal adhesion kinase
      (p125FAX) and paxillin, two molecules involved in the early signaling and
      cytoskeleton assembly in cells that undergo integrin-mediated adhesion or are
      challenged by neuropeptides or lysophosphatidic acid. The phenomenon is rapidly
      turned on, lasts for a few minutes and is adhesion-independent indicating that
      the chain of events induced by (R)PAF, including p125FAK activation, precedes
      adhesion. The inhibitory effect of WEB2086, a PAF receptor antagonist, and the
      lack of activity exerted by the (S)PAF enantiomer, indicate that (R)PAF-mediated
      p125FAK activation, is PAF receptor-dependent. Calphostin C, an inhibitor of
      protein kinase C blocks the effect of (R)PAF on p125FAK phosphorylation
      suggesting that protein kinase C activation is up-stream the activation of this
      tyrosine kinase. When endothelial cells are exposed to a substratum that allows
      adhesion and spreading. (R)PAF-stimulated cells, change their adhesive phenotype
      and start migrating. Inhibitors of tyrosine kinases, like 3-(1,4,
      dihydroxytetralyl) methylen-2-oxindole and herbimycin A, reduce the cells
      migration, the transendothelial flux of albumin and the enhancement of p125FAK
      activity induced by (R)PAF. The observation that increased tyrosine
      phosphorylation of p125FAK and its ensuring association with focal adhesion
      occurs rapidly upon (R)PAF challenge indicates that this signaling molecule has a
      primary and independent role also in the signaling cascade initiated by (R)PAF.

PMID- 8760294
TI  - SV40-like sequences in human bone tumors.
AB  - Simian virus 40 (SV40) is a monkey virus that induces ependymomas, choroid plexus
      tumors, mesotheliomas, osteosarcomas, sarcomas and true histiocytic lymphomas
      when injected in hamsters. Recently, approximately 60% of human ependymomas,
      choroid plexus tumors and mesotheliomas were reported to contain and express SV40
      like sequences (N. Engl. J. Med., 1992, 36, 988-993; Oncogene, 1994, 9, 1781
      1790). In this study the presence of SV40-like sequences was investigated in
      additional types of human tumors. Initially, 200 tumor and normal tissue DNA
      samples were analysed by polymerase chain reaction (PCR) with primers that
      amplify a 574 base pair region of SV40 large T antigen (Tag), which includes the
      Rb-pocket binding domain and the intron of Tag. PCR amplification and Southern
      blot hybridization with a probe specific for SV40 Tag revealed that 18/200
      samples contained SV40-like sequences and, unexpectedly, 11/18 were from patients
      with osteosarcomas. Additional DNA samples from bone tumors were then analysed.
      In 40/126 osteosarcomas, and 14/34 other bone-related tumors, Tag sequences could
      be amplified. Sequence analysis of the DNA amplified from seven different tumors
      confirmed that the amplified sequences corresponded to SV40 Tag, with some
      demonstrating deletions in the intron region but not in the Rb-pocket binding
      domain. The extent of SV40 genome sequences present in the DNA samples was
      further analysed in two osteosarcomas. PCR amplification, Southern blot
      hybridization, and sequence analysis revealed that these samples also contained
      sequences for the carboxy-terminal domain of Tag, the viral regulatory region,
      and the VP1 capsid protein. These results indicate that SV40-like sequences are
      present in human bone tumors.

PMID- 8760295
TI  - Anti-oncogenic effects of tropomyosin: isoform specificity and importance of
      protein coding sequences.
AB  - Suppression of muscle type isoforms of tropomyosin (TM) is a common biochemical
      event in malignantly transformed cells. To evaluate the role of TM proteins and
      isoform specificity in cellular transformation, cDNAs that consist of coding
      sequences of TM1 (product of beta gene) and TM2 (product of alpha gene), but
      lacking untranslated regions (UTRs), have been expressed separately in DT (v-Ki
      ras transformed NIH3T3) cells, and elevated levels of the corresponding proteins
      were detected. DT cells which over express TM2 manifest growth in soft agar.
      Elevated levels of TM1 protein in DT cells resulted in flattened cell morphology
      and complete abolition of anchorage independent growth. Tumorigenesis in athymic
      nude mice was observed in the absence of transduced TM1 mRNA. Thus, expression of
      TM1 protein is sufficient for tumor suppression: the UTRs of TM1 are not required
      for the tumor suppressive effects. Expression of TM2 protein, on the other hand,
      has no effect on the transformed phenotype of DT cells. These data indicate that
      isoforms 1 and 2 of TMs perform distinct physiological roles.

PMID- 8760296
TI  - The apical membranes of maturing gut columnar epithelial cells contain the
      enzymatically active form of a newly identified fyn-related tyrosine kinase.
AB  - Recently, we isolated a new src family member from a rat small intestinal cDNA
      library which by RNase protection analysis is selectively expressed in the
      columnar epithelium of gut. Complete nucleotide sequencing of the
      gastrointestinal associated tyrosine kinase (gtk) has revealed that it is a rat
      homologue of frk/rak-a fyn related human tyrosine kinase. Unlike frk/rak, gtk is
      myristylated, in vivo. Furthermore, by immunohistochemical analysis, the kinase
      is concentrated in the brush border membranes of epithelial cells, throughout the
      maturation axis of the adult small intestine. In vitro analysis revealed that gtk
      kinase activity is present in intestinal cells throughout their maturation,
      suggesting that the enzyme might influence signal transduction pathways in both
      mitotic and post-mitotic states. Gtk is expressed in all regions of the
      gastrointestinal tract which contain columnar epithelium, but is absent in the
      stratified epithelium of the esophagus. Moreover, during gestation, the kinase
      dramatically appears at high levels in plasma membranes, at the time of
      transition of gut cells from an undifferentiated to a simple columnar phenotype.
      After solubilization of cellular membranes with Triton X-100, sucrose gradient
      analysis of gtk revealed that it partitions differently than c-yes, demonstrating
      that the brush border src kinases associate with different components of the
      plasma membranes. These findings suggest that gtk plays a specialized role in the
      growth/differentiation of gut columnar epithelial cells.

PMID- 8760297
TI  - Inhibition of SV40 T antigen-induced hepatocellular carcinoma in TIMP-1
      transgenic mice.
AB  - The potential of tissue inhibitors of metalloproteinases (TIMPs) to inhibit
      neoplastic progression has been postulated from studies of genetically
      manipulated cells. To investigate whether the TIMP-1 expressed in a host tissue
      suppresses cancer in vivo and to identify the affected stages, we developed
      transgenic mice with constitutive overexpression or reduction of TIMP-1 in the
      liver. In double transgenic experiments, the TIMP-1 lines were crossed with a
      second transgenic line which expresses the Simian Virus 40t/T antigen (TAg). This
      viral oncogene leads to heritable development of hepatocellular carcinomas with a
      100% incidence. Effects of TIMP-1 coexpression on the TAg-induced neoplasms were
      determined at the tissue and cellular level. Here, we report that overexpression
      of hepatic TIMP-1 blocked the development of TAg-induced hepatocellular
      carcinomas. High TIMP-1 levels inhibited not only the later stages in tumor
      development (growth and angiogenesis), but also events associated with tumor
      initiation (altered hepatocyte cytology and tissue architecture). We further show
      that an antisense-mediated reduction of TIMP-1 resulted in a more rapid tumor
      initiation and progression. These data demonstrate that intrinsic TIMP-1 levels
      contribute to a tissue's susceptibility to viral oncogene-induced tumorigenesis.

PMID- 8760298
TI  - Association of CDKN2A/p16INK4A with human head and neck keratinocyte replicative
      senescence: relationship of dysfunction to immortality and neoplasia.
AB  - We have previously suggested that a gene mapping to chromosome 9p21 could
      contribute to replicative senescence and suppress cullular immortality in
      squamous neoplasia. Two candidate genes, the cyclin D1/cyclindependent kinase
      inhibitors CDKN2A/p16INK4A (p16) and CDKN2B/p15INK4B (p15) have now been
      identified in this region and we show here that p16 is upregulated when normal
      human keratinocytes undergo replicative senescence but not when they undergo
      differentiation. Furthermore, all of 19 immortal neoplastic keratinocyte head and
      neck lines, including nine showing loss of heterozygosity (LOH) at 9p21, showed
      undetectable p16 expression, whereas five of six senscent neoplastic cultures
      showed normal levels of expression. The retinoblastoma protein (pRb) appeared
      functional in all the cell lines and cultures examined. The mechanism of p16
      inactivation appeared to be transcriptional silencing in 10 of 18 lines and
      homozygous deletions in the rest. Treatment of two of the immortal cell lines
      which had transcriptionally silent wild type p16 genes with 5aza-2deoxycytidine
      resulted in the re-expression of p16, thus implicating DNA methylation as one
      mechanism of transcriptional silencing in the immortal SCC-HN lines. We observed
      no cases of p16 point mutation. In contrast, the p15 gene was rarely
      transcriptionally silent and was not deleted in any of the cell lines which
      showed p16 deletions. Our results show that p16 dysfunction correlates strongly
      with keratinocyte immortalisation but less strongly with the stage of tumour
      progression. P16 dysfunction was not related to the neoplastic state or the
      length of time spent in vitro. The results also suggest that p16 but not p15 is
      involved in the keratinocyte replicative senescence programme. However, two
      neoplastic cell cultures which lacked p16 expression were still mortal,
      suggesting that the loss of p16 is a necessary but insufficient condition for
      human keratinocyte immortality.

PMID- 8760299
TI  - Neovascularization in human germ cell tumors correlates with a marked increase in
      the expression of the vascular endothelial growth factor but not the placenta
      derived growth factor.
AB  - Neoangiogenesis is a prerequisite for tumor growth and metastasis. In germ cell
      cancer patients with the disease limited to the testicle (stage A), tumor
      associated neovascularization is predictive of metastatic disease (stage B). To
      investigate the molecular mechanisms underlying neovascularization in human germ
      cell tumors (GCTs), we analysed the expression of two angiogenic growth factors,
      vascular endothelial growth factor (VEGF) and placenta growth factor (P1GF), and
      of their receptors (FLT-1) and Flk-1/KDR) in a panel of testicular tumors. In
      this study we show a marked increase in VEGF expression in 36/44 (81.8%) primary
      testicular-derived GCTs, as compared to normal testis, that significantly
      correlates with a high density of intratumor microvessels (r = 0.72461, P <
      0.001; n = 24). As determined by RT - PCR and/or Western blot, the predominant
      VEGF isoforms expressed in GCTs are the VEGF121 and VEGF165, which are more
      efficiently secreted by the cells, and thus more active in eliciting
      angiogenesis. Conversely, in the case of PIGF, only a weak correlation with the
      vascular density of tumors is observed (r = 0.26599, P < 0.05; n = 24). Northern
      blot analysis also revealed significant up-regulation of VEGF/ PIGF receptors in
      highly vascularized germ cell tumors, compared to normal testes. These findings
      suggest that VEGF may act in a paracrine manner to induce neovascularization,
      oedema extravasation and cyst formation in human germ cell tumors. The
      correlation between VEGF expression and the vascular density of tumors, suggest
      that the evaluation of VEGF expression may be of help in predicting patients at
      risk for metastatic diseases. Finally, we demonstrate that VEGF up-regulation may
      occur at the RNA level since no gene amplification is observed; conversely, in in
      vitro models such as the embryonal stem cell line NTERA-2 and the choricarcinoma
      JEG-3 cell line, VEGF (but not PIGF) mRNA expression is regulated by hypoxic
      stress.

PMID- 8760300
TI  - Selective loss of endogenous p21waf1/cip1 induction underlies the G1 checkpoint
      defect of monomeric p53 proteins.
AB  - Wild-type p53 protein displays a spectrum of activities including the ability to
      suppress transformed cell growth to direct apoptotic cell death and to mediate G1
      checkpoint in response to cellular DNA damage. Earlier work showed that a self
      association defective p53 protein retained transformation suppressor activity in
      rat embryo fibroblast based assays, but that monomerisation of tumour mutant p53
      proteins resulted in loss of dominant transforming activity. In order to acquire
      a more detailed understanding of the biological consequences attendant on
      disruption of p53:p53 association we have carried out a study of the wild-type
      like activities that are retained by monomeric p53 proteins and which are
      associated with the suppression of transformation. Here we show that monomeric
      p53 proteins are G1 checkpoint defective. Although able to stimulate
      transcription via a p53 DNA binding motif from the p21waf1/cip1 gene promoter in
      episome based assays these p53 proteins are unable to transactive the chromosomal
      p21waf1/cip1 gene and are sensitive both to degeneracy of consensus binding site
      and to half site spacing. Monomeric p53 proteins fail to trigger apoptosis in a
      BRK cell line transformed with E7 and ras. However, they retain wild type
      transformation suppressor activity in BRK cell based transformation assays. Our
      results indicate that p21waf1/cip1 induction and all related p53 dependent G1
      checkpoint activities are dispensable for the p53 directed suppression of
      transformed cell growth, and that such transformation suppression by monomeric
      p53 proteins may occur in the absence of an apoptotic response.

PMID- 8760302
TI  - Differential regulation of p53, c-Myc, Bcl-2 and Bax protein expression during
      apoptosis induced by widely divergent stimuli in human hepatoblastoma cells.
AB  - Apoptosis of HepG2 cells triggered by various agents is characterized in an
      attempt to delineate the common apoptosis signaling pathway in human hepatoma
      cells. Several hallmarks of apoptosis, including DNA laddering, chromatin
      condensation and fragmentation, and an apoptosis specific cleavage of 28S and 18S
      ribosomal RNA were observed after treatment with curcumin. Curcumin treatment
      however did not alter the expression levels of Bcl-2 and Bax proteins. p53
      protein accumulated slowly and decreased abruptly after reaching the maximum.
      Conversely, c-Myc protein decreased initially and subsequently increased
      preceding the onset of apoptosis. The accumulation of p53 protein is not due to
      increased levels of p53 mRNA and does not result in growth arrest. Staurosporine,
      quinacrine, ultraviolet irradiation, hydrogen peroxide, and cyclohexamide are all
      capable of triggering apoptosis in HepG2 cells. While most of these agents affect
      the expression levels of p53 and c-Myc similarly, none of them altered the
      expression levels of the Bcl-2 and Bax proteins. In conclusion, these data
      suggest that p53 and c-Myc may play a more important role in the apoptosis
      signaling pathway in HepG2 cells, than the bcl-2 gene family.

PMID- 8760303
TI  - The TAL1/Scl basic helix-loop-helix protein blocks myogenic differentiation and E
      box dependent transactivation.
AB  - The TAL1 gene is transcriptionally activated by chromosomal translocation in the
      most common genetic lesion associated with T-cell acute lymphoblastic leukemia.
      TAL1 encodes a bHLH protein that exhibits sequence-specific DNA binding activity
      when it forms dimers with another bHLH protein such as E2A. We show that ectopic
      expression of TAL1 blocks the ability of the bHLH gene myogenin to induce myotube
      differentiation in C3H10T1/2 cells. Cotransfection of TAL1 with either myogenin
      or E2-5 suppresses the transcriptional activation function of each gene on its
      respective reporter constructs. TAL1 was as effective as Id in both
      transcriptional suppression and inhibition of differentiation. Deletion of the C
      terminal domain of TAL1 reduces or eliminates its ability to suppress
      transcription while preserving the bHLH domain that determines the sequence
      specificity of DNA binding. These data suggest that the C-terminal domain of TAL1
      may directly mask the transactivation domain of E2A-related proteins. Since E2A
      related genes are involved in lymphocyte differentiation, the dominant inhibition
      of E2A-related proteins may be the primary mechanism by which the TAL1 oncogene
      promotes leukemia.

PMID- 8760301
TI  - Differential regulation of cell cycle machinery by various antiproliferative
      agents is linked to macrophage arrest at distinct G1 checkpoints.
AB  - There is currently much interest in the mechanisms of action of antiproliferative
      agents and their effects on cell cycle machinery. In the present study we
      examined the mechanisms of action of four unrelated agents known to inhibit
      proliferation of CSF-1-stimulated bone marrow-derived macrophages (BMM). We
      report that 8-bromo-cAMP (8Br-cAMP) and lipopolysaccharide (LPS) potently reduced
      CSF-1-stimulated cyclin D1 protein, and cyclin-dependent kinase (cdk) 4 mRNA and
      protein levels, while the inhibitory effects of the Na+/ H+ antiport inhibitor 5
      (N',N'-dimethyl) amiloride (DMA) and interferon gamma (IFN gamma ) were only
      weak. All agents repressed CSF-1-stimulated retinoblastoma protein
      phosphorylation. Furthermore, 8Br-cAMP and to a lesser extent IFN gamma, also
      reduced CSF-1-stimulated levels of E2F DNA binding activity in a macrophage cell
      line, BAC1.2F5. An explanation for the different effects of the agents is that
      8Br-cAMP and LPS were found to arrest BMM in early/mid-G1, while IFN gamma and
      DMA arrested cells in late G1 or early S phase. These data indicate that (1)
      different antiproliferative agents can arrest the same cell type at distinct
      checkpoints in G1 and (2) effects of antiproliferative agents on cell cycle
      machinery is linked to the position at which they arrest cells in G1.

PMID- 8760304
TI  - Distinct p53-mediated G1/S checkpoint responses in two NIH3T3 subclone cells
      following treatment with DNA-damaging agents.
AB  - N3T3 and P-3T3 cells, originally isolated from a NIH3T3 cell clone on the basis
      of their negative and positive transformation by v-Abl, v-Src and Bcr-Abl, were
      previously found to show distinct cyclin activity changes following 12-O
      tetradecanoylphorbol-13-acetate (TPA) treatment, which is anti-mitogenic for N
      3T3 cells and mitogenic for P-3T3 cells. We have found in this study that, while
      the G1/S arrest and cell death induced by serum starvation and TPA treatment in N
      3T3 cells did not involve p53-mediated checkpoint or apoptosis, N-3T3 and P-3T3
      cells evidently responded differently in these aspects of cell cycle regulation
      to DNA-damaging agents, methylmethane sulfonate (MMS) and gamma-radiation. In N
      3T3 cells, DNA damages elicit cell growth arrest at G1/S transition with
      concomitant accumulation of p53 and p53-inducible Waf1/Cip1 proteins and also
      signs of apoptosis such as DNA ladder patterns and apoptotic (subgenomic) peak in
      flow cytograph. Conversely, P-3T3 cells treated with the DNA-damaging agents
      showed no cell cycle interruption nor accumulation of p53 or Waf1/Cip1. However,
      both P-3T3 and N-3T3 cells showed the same p53 protein half-life of 40 min or
      less, the same wild-type p53 DNA sequence and the same co-immunoprecipitable
      cellular proteins in complexes with p53, suggesting that an alteration in a
      signal transduction pathway upstream of p53 might account for the evasion of p53
      mediated G1 checkpoint in P-3T3 cells.

PMID- 8760305
TI  - A family of Shc related proteins with conserved PTB, CH1 and SH2 regions.
AB  - Shc proteins are targets of activated tyrosine kinases and have been implicated
      in the transmission of activation signals to Ras. Upon phosphorylation, Shc
      proteins form stable complexes with cellular tyrosine-phosphorylated proteins and
      with the Grb2 adaptor protein. Two Shc isoforms of 52 and 46 kDa have been
      characterized. They share a C-terminal SH2 domain, a proline- and glycine-rich
      region (collagen homologous region 1; CH1) and a N-terminal phospho-tyrosine
      binding domain (PTB). We report her ethe initial characterization of two Shc
      related human cDNAs: ShcB and ShcC. The ShcB and ShcC cDNAs code for proteins
      that are highly similar and share the same modular organization as Shc. PTB and
      SH2 domains of ShcB and ShcC have similar binding specificities in vitro and bind
      to activated EGFR in a phosphotyrosine-dependent manner. Based on these findings
      we propose to rename Shc as ShcA. Anti-ShcB and anti-ShcC antibodies recognize
      specific polypeptides of 52, 47 kDa (ShcB) and 54 kDa (ShcC) in mammalian cells.
      Since these two genes are predominantly expressed in specific brain tissues,
      these Shc family members may be involved in cell type-specific signaling, in the
      nervous system.

PMID- 8760306
TI  - Isolation and characterization of the mouse homolog of SYT, a gene implicated in
      the development of human synovial sarcomas.
AB  - In a previous study we reported the isolation of the human synovial sarcoma
      associated t(X;18) breakpoint. As a result of this translocation, the SYT gene on
      chromosome 18 fuses to either the SSX1 or the SSX2 gene on the X chromosome,
      depending on the exact location of the breakpoint within band Xp11.2. As yet,
      little is known about the modes of action of the SYT and SSX genes and their
      respective (fusion) products. Here we report the isolation of the mouse homolog
      of SYT, its full length cDNA sequence, its chromosomal localization, and its
      spatio-temporal expression patterns in adult and embryonic tissues. The SYT gene
      was found to be well conserved during evolution and is part of a region of
      synteny between the human and mouse chromosomes 18. In early embryogenesis, Syt
      is ubiquitously expressed. In later stages, the expression becomes confined to
      cartilage tissues, specific neuronal cells and some epithelial derived tissues.
      In mature testis, expression was specifically observed in primary spermatocytes.

PMID- 8760307
TI  - BRCA1 mRNA is expressed highly during meiosis and spermiogenesis but not during
      mitosis of male germ cells.
AB  - The 17q-linked breast and ovarian cancer susceptibility gene (BRCA1) is believed
      to function as a tumor suppressor gene (Miki et al., 1994). In this report BRCA1
      RNA expression has been analysed in adult mouse tissues with detailed attention
      to its expression in prepuberal and adult testis. Measurements of BRCA1 mRNA
      levels in highly purified somatic cells of the testis and in staged germ cells
      showed that high level BRCA1 mRNA expression is limited to the germ cells. Within
      the germ cell lineage, the high level expression was detected in meiotic cells,
      specifically pachytene spermatocytes and in post-meiotic round spermatids. This
      is in contrast to premeiotic germ cells which were found to express little or no
      BRCA1 mRNA. These observations, considered together with recent data on the
      expression of BRCA1 in breast epithelium, argues against a function for BRACA1 in
      early progenitor cells in both tissues and cells attention instead to roles
      intimately associated with terminal differentiation or with final rounds of cell
      division.

PMID- 8760308
TI  - Induction of p53 and increased sensitivity to cisplatin in ataxia-telangiectasia
      cells.
AB  - Several reports have demonstrated a defective p53 response to ionizing radiation
      exposure in ataxia-telangiectasia (A-T) cells. On the other hand, p53 induction
      was normal after u.v. irradiation, an agent to which A-T cells are not
      hypersensitive. We show here that A-T cells are more sensitive than normal
      lymphoblastoid cells to cisplatin treatment but the rate of induction of p53 by
      cisplatin is similar in both cell types. In addition, the half-life of p53, both
      in the induced and uninduced forms, is the same in A-T and normal lymphoblastoid
      cells. The use of a reporter assay to determine the functional status of p53
      confirmed the results obtained in the induction experiments with cisplatin. These
      results demonstrate that p53 induction status in A-T cells does not correlate
      with sensitivity to the inducting agent and there is no inherent defect in the
      turn-over of p53 in the induced or uninduced states in A-T.

PMID- 8760309
TI  - Abnormalities of p16, p15 and CDK4 genes in recurrent malignant astrocytomas.
AB  - Abnormalities in the p16, p15 and CDK4 genes that regulate transition through the
      G1 phase of the cell cycle have been implicated in the malignant progression of
      astrocytomas. The results of the present study demonstrate that dysfunction of
      these genes also occurs during recurrence of glial tumors that were highly
      malignant at first presentation. Analysis of 10 matched pairs of high grade
      malignant astrocytomas and their subsequent recurrences identified three distinct
      groups. The primary and recurrent tumors in Group A did not show structural
      alterations in the p16, p15 or CDK4 genes, whereas homozygous codeletion of p16
      and p15 was observed in both primary and recurrent tumors in Group B. The primary
      tumors in Group C had a normal profile of p16, p15 and CDK4 at presentation. Upon
      recurrence, however, the tumors sustained either deletion of p16 alone or
      codeletion of both p16 and p15 or amplification of CDK4. Analysis of the
      molecular differences between primary anaplastic astrocytomas/glioblastomas and
      their subsequent recurrences, which are clinically indistinguishable, may provide
      better therapeutic options for treatment.

PMID- 8760310
TI  - The effect of infection with Lyme disease spirochetes (Borrelia burgdorferi) on
      the phototaxis, activity, and questing height of the tick vector Ixodes
      scapularis.
AB  - Little is known about the effects of infection with Borrelia burgdorferi, the
      bacterium that causes Lyme disease, on its tick vectors. The purpose of this
      study was to determine the behavioural and ecological effects of infection by the
      bacterium in nymphal and adult black-legged (Ixodes scapularis) ticks. We found
      that the effects of infection were more pronounced in adults than in nymphs.
      Compared to uninfected adults, infected adults were less able to overcome
      physical obstacles, avoided vertical surfaces, were less active and quested at
      lower heights. Infected nymphs showed increased phototaxis and attraction to
      vertical surfaces. Infected nymphs also showed trends toward increased questing
      height and a greater tendency to overcome physical obstacles although these
      trends were not statistically significant. These altered behaviours in an
      infected tick may affect survival or pathogen transmission and may reflect kin
      selection in the bacterial pathogen.

PMID- 8760311
TI  - Malaria parasites enhance blood-feeding of their naturally infected vector
      Anopheles punctulatus.
AB  - We investigated the blood-feeding behaviour of a natural population of the human
      feeding mosquito Anopheles punctulatus in Iguruwe, Papua New Guinea. In
      particular we investigated the relationship between the mosquitoes' blood-feeding
      behaviour and their infection by the malaria parasites Plasmodium falciparum and
      P. vivax. Female mosquitoes were caught at 4 times of the night, the amount of
      blood they had obtained was measured and their status of infection was evaluated.
      Among uninfected mosquitoes the bloodmeal size steadily increased through the
      night, possibly because they were progressively less likely to be disturbed by
      human activity as the night drew on. Infected mosquitoes, on the other hand,
      tended to feed maximally at all times of the night. This suggests that infected
      mosquitoes were more tenacious in their blood-feeding behaviour, being either
      less readily disturbed during a bout of feeding (and thus feeding longer) or more
      likely to return to continue their feed following disturbance (and thus feeding
      several times). Either change would increase the parasites' rate of transmission.
      We conclude that in this natural situation the two species of malaria parasites
      modified the mosquitoes' behaviour with the effect of increasing their own
      transmission.

PMID- 8760312
TI  - Pharmacology and efficacy of liposome-entrapped albendazole in experimental
      secondary alveolar echinococcosis and effect of co-administration with
      cimetidine.
AB  - Encapsulation of the benzimidazole albendazole in multilamellar liposomes results
      in a preparation in which this normally insoluble anti-hydatid drug is well
      solublilized in aqueous media. The high entrapment efficiency observed (75-87%)
      and the stability of the formulation make this a promising delivery vehicle for
      improved chemotherapy with albendazole. In particular, the high degree of
      association with phospholipid may give rise to increased oral bioavailability.
      Oral administration of albendazole in liposomes led to increased concentration
      and/or altered metabolism of albendazole sulphoxide (ABZSX) in liver and/or
      plasma in non-infected Wistar rats. Results from experiments using cotton rats
      (Sigmodon hispidus) infected with metacestodes of Echinococcus multilocularis
      show that entrapment within liposomes clearly increases the uptake of albendazole
      via the oral route. This was reflected by increased levels of albendazole and the
      two major metabolites in plasma, liver and cyst homogenate when a dose of
      liposomal albendazole (35 mg/kg) was given orally compared to free albendazole at
      50 mg/kg. There was a 75-94% reduction in biomass of the metacestode and a
      significant increase in survival time for the animals treated with liposome
      entrapped albendazole. A clear difference in distribution of albendazole and its
      metabolites in the liver and the metacestode tissues in the presence of
      cimetidine indicated that the latter has a profound effect on the metabolism of
      albendazole. There appeared to be a synergistic interaction between albendazole
      and cimetidine, since the metabolism of albendazole was markedly altered in the
      combined cimetidine/ liposome-albendazole group, and higher therapeutic effect
      was observed. These findings indicate potential both for improvement of treatment
      of larval E. multilocularis infection and for reduction of albendazole dose
      levels.

PMID- 8760313
TI  - Competitive exclusion in human schistosomes: the restricted distribution of
      Schistosoma intercalatum.
AB  - A study on the immune and mating interactions between Schistosoma intercalatum
      and S. mansoni has been carried out. The immunologically mediated interactions
      and mating patterns observed between the two species demonstrate that S. mansoni
      is competitively dominant over S. intercalatum. When S. mansoni females are
      absent, S. mansoni males are more competitive than S. intercalatum males at
      pairing with S. intercalatum females. The use of a mathematical model shows how
      the abundance of S. mansoni worms per host could dramatically affect the mating
      probability of S. intercalatum females with their homologous males. It appears
      that the competitive exclusion between these two species of schistosomes may
      probably be an important factor restricting the distribution of S. intercalatum
      in Africa.

PMID- 8760314
TI  - Identification and sequence comparison of a cuticular collagen of Brugia pahangi.
AB  - The cuticle of filarial nematodes is a specialized extracellular matrix that
      covers the parasite and protects it from adverse conditions of the environment.
      As a surface structure it is in direct contact with the host defence mechanisms
      and therefore plays an important role in the molecular host-parasite
      relationship. Using polyclonal antisera raised against the insoluble components
      of the cuticle of the adult filarial parasite Brugia pahangi, we have isolated
      cDNA clones encoding collagen molecules of the cuticle. The protein domain
      structure of cDNA clone Bpcol-1 was compared with the known structures of
      cuticular collagens of the nematodes Brugia malayi, Caenorhabditis elegans,
      Ascaris suum and Haemonchus contortus, confirming interspecies similarities.
      Using affinity-purified anti-Bpcol-1 antibodies we identified Bpcol-1 antigenic
      determinants in different nematode extracts, and determined the localization of
      such epitopes within the cuticle of B. pahangi.

PMID- 8760315
TI  - Immunodominance, competition and evolution in immunological responses to helminth
      parasite antigens.
AB  - The paper describes the development and analysis of a mathematical framework for
      the study of the within-host population dynamics of the interaction between
      macroparasites and the human immune system. Simple models of this interaction
      based on the proliferation of T cell clones specific to parasite antigen, and the
      impact of clonal expansion on parasite survival, capture the basic features of
      age-related changes in worm loads within human communities. The model is
      generalized to multiple epitopes on a single antigen, and reveals competitive
      exclusion amongst T cells, with a single clone becoming immunodominant in the
      absence of cross-reactive responses and genetic variation. The introduction of
      genetic heterogeneity and concomitant variability in the immunogenicity of
      specific epitopes induces additional complexity into the dynamical interaction.
      Most importantly, multiple epitope models with antigenic variation suggest that
      the immunodominant response may not necessarily be targeted at the epitope at
      which some strains show the greatest immunogenicity. High immunogenicity at a
      particular epitope can be masked by genetic variability even though many of the
      variants are more immunogenic at this epitope by comparison with the epitope to
      which the immunodominant immunological response is directed.

PMID- 8760316
TI  - Nippostrongylus brasiliensis infection evokes neuronal abnormalities and
      alterations in neurally regulated electrolyte transport in rat jejunum.
AB  - Neuronal abnormalities have been described in the intestine of helminth-infected
      rats. However, the physiological ramifications of these changes have not been
      determined. Here, we examined epithelial ion secretion, indicated by increases in
      short-circuit current (Isc), evoked by electrical transmural stimulation (TS) of
      enteric nerves in Ussing-chambered jejunal tissues from Nippostrongylus
      brasiliensis-infected rats. Rats were examined at 10 and 35 days post-infection
      (p.i.); non-infected rats served as controls. TS resulted in significantly
      reduced ion secretion in jejunum from 10 day p.i. rats compared to controls or
      jejunum from 35 day p.i. rats. The TS response in tissue from infected rats had,
      unlike controls, no cholinergic component. Tissues from both non-infected and
      infected rats were equally responsive to the muscarinic agonist bethanechol,
      suggesting that the cholinergic defect was neuronal and not an inability of the
      epithelium to respond to cholinergic stimulation. However, increases in Isc
      evoked by exogenous substance P (SP) in tissue from rats 10 day p.i. were reduced
      in magnitude to approximately 25% of control values. Concomitant with these
      physiological changes, tissue from infected rats contained increased amounts of
      substance P immunoreactivity and intestinal sections displayed increased numbers
      of substance P-immunoreactive nerve fibre profiles at both 10 and 35 days p.i.
      Thus, following N. brasiliensis infection there is a shift in the enteric nervous
      system away from cholinergic to non-cholinergic regulation, associated with
      increased amounts of the pro-inflammatory neuropeptide, substance P. We speculate
      that changes in neuronal structure and function are intimately involved in the co
      ordinated multicellular response to intestinal parasitic infection and subsequent
      gut recovery.

PMID- 8760318
TI  - Effects of pH on a high conductance Ca-dependent chloride channel: a patch-clamp
      study in Ascaris suum.
AB  - Plasma membrane vesicles prepared from the bag region of the somatic muscle cells
      of the parasitic nematode Ascaris suum contain high conductance, voltage
      sensitive, Ca-dependent chloride channels, suggested to be involved in the
      excretion of carboxylic acids produced by the anaerobic respiration of glucose
      (Valkanov, Martin & Dixon, 1994). The effect of altered pH on this channel was
      investigated using the patch-clamp technique and isolated inside-out membrane
      patches. Changes in pH had little effect on channel conductances and only a small
      effect on reversal potentials. Under control conditions (symmetrical pH 7.2) the
      channel had the highest probability of opening at approximately -35 mV (the
      resting membrane potential of the cell). At positive membrane potentials the
      probability of opening decreased. The Boltzmann equation was used to describe the
      relationship between membrane potential and probability of channel opening, and
      to calculate the effective gating charge. Reduction of external pH produced an
      increase in the probability of channel opening at hyperpolarized membrane
      potentials. An increase in internal pH caused a voltage-independent increase in
      the probability of channel opening and made the effective gating charge less
      negative. The effect of reducing internal pH was marked: the channel then opened
      most frequently at positive membrane potentials and the probability of opening at
      -35 mV was greatly reduced. The decrease in internal pH changed the polarity of
      the effective gating charge. A simple model was constructed to describe the
      effects of pH on channel gating.

PMID- 8760320
TI  - Application of antimicrobial-producing lactic acid bacteria to control pathogens
      in ready-to-use vegetables.
AB  - Five psychrotrophic strains of lactic acid bacteria (Lactobacillus casei, Lact.
      plantarum and Pediococcus spp.) were isolated from 22 samples of commercial
      salads. These strains were shown to inhibit Aeromonas hydrophila, Listeria
      monocytogenes, Salmonella typhimurium and Staphylococcus aureus on MRS agar, in
      salads and in juice prepared from vegetable salads. Lactobacillus casei IMPCLC34
      was most effective in reducing total mesophilic bacteria and the coliform group;
      Aer. hydrophila, Salm. typhimurium and Staph. aureus disappeared after 6 d of
      storage, while the counts for L. monocytogenes remained constant. The potential
      application of antimicrobial-producing lactic acid bacteria as biopreservatives
      of ready-to-use vegetables is suggested.

PMID- 8760321
TI  - The effect of chlorhexidine on defined, mixed culture oral biofilms grown in a
      novel model system.
AB  - In order to develop an improved method to evaluate antimicrobial agents for use
      in clinical dentistry, a constant-depth film fermenter (CDFF) has been used to
      generate biofilms of fixed depth comprising nine species of bacteria commonly
      found in dental plaque in health and disease. These bacteria were grown together
      initially in a conventional chemostat which was used to inoculate the CDFF over
      an 8 h period. Medium was then supplied directly to the CDFF and biofilms allowed
      to develop. The biofilms were then challenged with eight short pulses of two
      concentrations of chlorhexidine (0.0125 and 0.125% w/v). The lower concentration
      had a limited effect on the composition of the biofilms while a differential and
      substantial inhibition was obtained with a higher concentration. Actinomyces
      naeslundii was lost from the biofilm, and the viable counts of streptococci,
      Fusobacterium nucleatum and Porphyromonas gingivalis were inhibited by over three
      orders of magnitude by 0.125% chlorhexidine, whereas Veillonella dispar was only
      transiently affected. The findings were consistent with those from clinical
      studies of dental plaque, suggesting that this model would have a predictive
      value when evaluating novel antiplaque or antimicrobial inhibitors.

PMID- 8760322
TI  - Development of a method based on alkaline gel electrophoresis for estimation of
      oxidative damage to DNA in Escherichia coli.
AB  - A method for estimating DNA strand breakage and subsequent repair based on
      alkaline gel electrophoresis was developed and tested with isogenic strains of
      Escherichia coli deficient in DNA repair enzymes. Samples from a cell suspension
      were removed at 2 min intervals following a 15 min exposure to 20 mmol l-1 H2O2.
      Catalase was added and the cells were embedded in blocks of low-melting point
      agarose and lysed. After alkaline gel electrophoresis, photographs of the gels
      were taken and the relative lengths of the distributions of DNA fragments were
      measured with a scanner and computer. The lengths were correlated with survival
      of the cells exposed to H2O2 and with the importance of particular DNA repair
      enzymes. Alkaline gel electrophoresis appears to be a relatively simple method
      for analysing the level of H2O2-caused DNA damage and repair in E. coli.

PMID- 8760324
TI  - Metabolic activities of Listeria monocytogenes in the presence of sodium
      propionate, acetate, lactate and citrate.
AB  - The effects of sodium propionate, acetate, lactate and citrate on cell
      proliferation, glucose and oxygen consumption, and ATP production in Listeria
      monocytogenes were investigated in growing and resting cells. Media pH was 6.7
      6.8. Growth inhibition increased while glucose consumption continued in the
      presence of > or = 1% propionate, > or = 3% acetate and > or = 5% lactate in
      broth during incubation at 35 degrees C, indicating that glucose consumption was
      uncoupled from cell proliferation. Acetate and propionate were the most effective
      antilisterials, whereas citrate (5%) was only slightly inhibitory. Of the four
      salts, only lactate supported growth, oxygen consumption and ATP production.
      While concentrations of 1 and 5% propionate, acetate and citrate did not have an
      effect on oxygen consumption, they inhibited ATP production. ATP production in
      the presence of the four salts was consistently lower at pH 6.0 than at neutral
      pH. Lactate served as an alternative energy source for L. monocytogenes in the
      absence of glucose but became toxic to the organism in the presence of the
      carbohydrate.

PMID- 8760323
TI  - Involvement of the cell envelope of Listeria monocytogenes in the acquisition of
      nisin resistance.
AB  - The involvement of the cell wall in the acquisition of nisin resistance by
      Listeria monocytogenes F6861 and its nisin-resistant mutant was investigated.
      Results indicated that without a cell wall, the acquired nisin resistance of the
      mutant was lost. Cell surface hydrophobicity was shown to correlate with nisin
      sensitivity; the wild type strain being more hydrophobic than its mutant. The
      possible role of S-layer proteins in nisin resistance was investigated.
      Examination of strains by freeze-etching and atomic force microscopy did not
      demonstrate the presence of S-layers in either strain while SDS-PAGE following S
      layer extraction procedures revealed no major protein bands. Chloramphenicol did
      not adversely affect the frequency of isolation of nisin-resistant mutants,
      indicating that de novo protein synthesis was not involved. The involvement of
      other cell surface components, teichoic and lipoteichoic acids, was also
      examined. In contrast with other reports, comparison of the total phospholipid
      content of the mutant with its parental strain showed no significant difference
      (P > 0.05).

PMID- 8760325
TI  - IS6501-anchored PCR for the detection and identification of Brucella species and
      strains.
AB  - A new strategy was developed to analyse the polymorphism of the genome of
      Brucella spp. All species of the Brucella genus contain several copies (between
      10 and 40) of an insertion sequence, IS6501 (known also as IS711). The position
      of copies of this insertion sequence appears to differ in each species and this
      can be used to discriminate between them. A new polymerase chain reaction test,
      called IS-anchored-PCR (IS-an-PCR) was developed. It was based on a combination
      of a primer bound on the sequence of IS6501 with a second primer chosen
      arbitrarily. The patterns obtained reflect the position of the insertion sequence
      in the genome. This method can be used to identify Brucella and to discriminate
      between different species, strains within a species and between the vaccine
      strain B19 and the corresponding 'wild-type' B. abortus A1.

PMID- 8760326
TI  - Effect of seawater on Escherichia coli beta-galactosidase activity.
AB  - An investigation of beta-galactosidase activity of Escherichia coli strain
      H10407, under different physiological and environmental conditions, e.g. induced
      and uninduced osmotic stress, light, etc., was undertaken. In this study E. coli
      was employed as a model for faecal coliforms in waste water. beta-Galactosidase
      activity was induced by isopropyl-beta-D-thiogalactoside (IPTG). Enzyme activity
      (U cell-1)/cell for sewage bacteria and for induced E. coli was similar, i.e. log
      U cell-1 = -8.5 whereas uninduced E. coli yielded log U cell-1 = -12.1. Initial
      enzyme activity was not dependent on phase of growth of the cell (exponential vs
      stationary phase) or whether marine or fresh water at the time of initial
      dilution. However, osmotic change resulted in a decrease in culturable cells,
      even though enzyme activity remained constant. A significant decrease in the
      number of culturable bacteria, followed by a decrease in beta-galactosidase
      activity, was observed after exposure of cells to visible light radiation. It is
      concluded that beta-galactosidase enzyme is retained in viable but non-culturable
      E. coli. Furthermore, beta-galactosidase appears to offer a useful and rapid (25
      min) measure of the viability of faecal coliforms, and therefore, of the water
      quality of bathing and shellfishing areas.

PMID- 8760328
TI  - Survival of Staphylococcus aureus and enterotoxin A in glassy and rubbery states
      of gelatin.
AB  - About 1% of Staphylococcus aureus cells survived the production of gelatin sheets
      containing nutrient broth. Those cells which survived showed no evidence of
      injury. Growth occurred in rubbery state gelatin with a(w) values of 0.98 and
      0.93 ; viability decreased during storage at a(w) values of 0.89, 0.62 and 0.36
      but there was little loss of viability in gelatin at an aw of 0.25 over 27 d
      storage at 26 degrees C. Assays for enterotoxin A detected no synthesis of new
      toxin but no loss in pre-formed toxin. The results suggest that high levels of
      Staph. aureus and its toxins should be excluded from glassy and rubbery state
      food products in order to prevent illness.

PMID- 8760327
TI  - Inhibition of Salmonella typhimurium by the products of tartrate metabolism by a
      Veillonella species.
AB  - The inhibition of the growth of Salmonella typhimurium by a Veillonella species
      grown on media supplemented with tartrate was examined. Growth of Salmonella
      typhimurium was not inhibited by the concentrations of products metabolized by
      Veillonella cultures on media supplemented with 0 or 50 mmol l-1 of tartrate, but
      was inhibited on media supplemented with 100 or 150 mmol l-1 of tartrate.
      Inhibition of Salm. typhimurium was correlated with the increased production of
      acetate and propionate from tartrate by the Veillonella species.

PMID- 8760329
TI  - Antimicrobial susceptibility and plasmid-mediated streptomycin resistance of
      Plesiomonas shigelloides isolated from blue crab.
AB  - Five Plesiomonas shigelloides strains isolated from retail or wild-catch
      Louisiana blue crabs (Callinectes sapidus) were examined for resistance to
      selected antibiotics and presence of plasmids. Three agar media, MacConkey,
      Salmonella-Shigella and a modification of inositol brilliant green bile salt
      (IBB), were evaluated for isolation of P. shigelloides. Of these, IBB was most
      satisfactory for distinguishing between P. shigelloides and the related species
      Aeromonas hydrophila. Isolates were susceptible to gentamicin, nalidixic acid and
      tetracycline, and were resistant to ampicillin, carbenicillin, kanamycin and
      streptomycin. Each isolate carried three plasmids of approximately 2.5 kb, 3.8 kb
      and 5.3 kb. Plasmid curing with ethidium bromide and elevated temperature linked
      the streptomycin resistance determinant with the 3.8 kb and/or 5.3 kb plasmids.
      These results provide the first description of small size plasmids in P.
      shigelloides. Identical antibiotic resistance patterns of the isolates indicated
      they share a common environment and likely share a common mode for developing
      antibiotic resistance. Furthermore, emergence of antibiotic-resistant P.
      shigelloides may imply contamination of Louisiana aquatic environments by
      wastewater.

PMID- 8760330
TI  - Effect of adherent Lactobacillus spp. on in vitro adherence of salmonellae to the
      intestinal epithelial cells of chicken.
AB  - Single strains of Lactobacillus acidophilus and Lact. fermentum, isolated from
      chicken intestine, were used to study in vitro interactions with Salmonella
      enteritidis, Salm. pullorum or Salm. typhimurium in an ileal epithelial cell
      (IEC) radioactive assay. Exclusion, competition and displacement phenomena were
      investigated by respectively incubating (a) lactobacilli and IEC together, prior
      to addition of salmonellae, (b) lactobacilli, IEC and salmonellae together, and
      (c) salmonellae and IEC, followed by the lactobacilli. Lactobacilli were selected
      for study because of their strong ability to adhere to IEC and poor aggregation
      with salmonellae. The results demonstrated that Lact. acidophilus significantly
      reduced (P < 0.05) the attachment of Salm. pullorum to IEC in the tests for
      exclusion and competition, but not in the displacement tests. Lactobacillus
      fermentum was found to have some ability to reduce the attachment of Salm.
      typhimurium to IEC under the conditions of exclusion (P < 0.08), competition (P <
      0.09), but not displacement. However, both Lact. acidophilus and Lact. fermentum
      were unable to reduce the adherence of Salm. enteritidis to IEC under any of the
      conditions.

PMID- 8760331
TI  - Note: microbial resistance of wool fabric treated with bis-Quats compounds.
AB  - In this paper, the antibacterial activity against Bacillus pumilus,
      Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa of the wool
      fabrics treated with new antimicrobial bis-quaternary surfactants, DABK and DABB,
      is studied. The activity was established on the basis of the agar diffusion and
      protective antibacterial test results and on the basis of scanning electron
      microscopy (SEM) observation. The results were compared with the HTAB, a
      monoquaternary surfactant of conventional use. The results from the agar
      diffusion and protective antibacterial tests do not enable us to confirm whether
      these compounds are potentially useful antimicrobial agents for the protection of
      textiles. However, SEM observations show clearly the efficacy of these compounds
      to protect the wool fabrics against the micro-organisms. SEM has been a useful
      technique for the assessment of antibacterial activity in textiles.

PMID- 8760332
TI  - Note: inhibition of the growth of Yersinia enterocolitica O:3 by the microflora
      of porcine caecum and ileum in an in vitro model.
AB  - The growth of Yersinia enterocolitica O:3 was tested in an in vitro model of the
      porcine intestine at the physiological temperature of 39 degrees C of growing
      pigs. The model supported a stable population of Y. enterocolitica at a level
      10(8)-10(9) cells ml-1. Plasmid profile analysis and the Ca(2+)-dependent
      proportion of the population suggested that the great majority of the Y.
      enterocolitica population retained the 70 kb virulence plasmid, pYV, throughout
      the experimental period of 5 d. The growth of Y. enterocolitica was substantially
      inhibited by the ileal and the caecal flora compared to the growth of the
      bacterium alone. Yersinia enterocolitica was not isolated after 3 d of
      cultivation.

PMID- 8760333
TI  - Adherens junctions in the Drosophila embryo: the role of E-cadherin in their
      establishment and morphogenetic function.
AB  - The integrity of epithelia depends largely on specialised adhesive structures,
      the adherens junctions. Several of the components required for building these
      structures are highly conserved between vertebrates and insects (e.g. E-cadherin
      and alpha- and beta-catenin), while others have so far been found only in
      invertebrates (e.g. crumbs). Two recent papers(1,2) show that the Drosophila E
      cadherin is encoded by the gene shotgun. Phenotypic analyses of shotgun as well
      as armadillo (beta-catenin) and crumbs mutants provide new insights into the
      mechanisms by which adherens junctions are built and, further, show that the
      requirement for E-cadherin largely depends on the morphogenetic activity of an
      epithelium.

PMID- 8760334
TI  - Signalling to p53: where does it all start?
AB  - Alterations in the p53 gene product appear to be a major factor in human
      tumorigenesis and may influence the responses of many human tumors to therapy.
      Much effort has focused on understanding the signals which normally initiate p53
      growth-suppressive functions. Though it has been known that DNA damage can induce
      p53, a recent publication reports data which suggest that p53 can be induced by
      depletion of ribonucleotide pools, even in the absence of detectable DNA
      damage(1). These observations provide new ideas about how cells utilize the p53
      signal and open up new avenues of investigation for manipulating p53 function.

PMID- 8760335
TI  - Lens development and crystallin gene expression: many roles for Pax-6.
AB  - The vertebrate eye lens has been used extensively as a model for developmental
      processes such as determination, embryonic induction, cellular differentiation,
      transdifferentiation and regeneration, with the crystallin genes being a prime
      example of developmentally controlled, tissue-preferred gene expression. Recent
      studies have shown that Pax-6, a transcription factor containing both a paired
      domain and homeodomain, is a key protein regulating lens determination and
      crystallin gene expression in the lens. The use of Pax-6 for expression of
      different crystallin genes provides a new link at the developmental and
      transcriptional level among the diverse crystallins and may lead to new insights
      into their evolutionary recruitment as refractive proteins.

PMID- 8760336
TI  - A new lease of life for an old enzyme.
AB  - We review here some recent data about glucose-6-phosphate dehydrogenase (G6PD),
      the first and key regulatory enzyme of the pentose phosphate pathway. New
      evidence has been presented to suggest that malaria is a selective agent for G6PD
      deficiency, which is the most common enzymopathy in man, and that G6PD
      deficiency, generally considered to be a mild and benign condition, is
      significantly disadvantageous in certain environmental conditions. At the
      molecular level, the enzyme structure has recently been elucidated and mechanisms
      regulating G6PD gene expression have been determined. A G6PD knock-out mutation
      introduced in mouse cells makes them exquisitely sensitive to oxidative stress,
      indicating that this ubiquitous metabolic enzyme has a major role in the defence
      against oxidative stress, even in eukaryotic nucleated cells, which have several
      alternative routes for providing the same protection. Because of the high
      prevalence of G6PD deficiency in many populations, it is expected that these
      findings will prompt further studies to ascertain the putative role of G6PD
      deficiency in conditions such as carcinogenesis and ageing.

PMID- 8760337
TI  - Promiscuity of fibroblast growth factor receptors.
AB  - Fibroblast growth factor receptors (FGFRs) have been implicated in many
      developmental and regenerative events, including axial organisation, mesodermal
      patterning, keratinocyte organisation and brain development. The consensus view
      that this reflects a role for one or other of the nine known members of the
      fibroblast growth factor family in these processes has recently been challenged
      by the suggestion that FGFRs might be directly activated by a much wider range of
      ligands, including heparan sulphate proteoglycans and neural cell adhesion
      molecules. In addition, two novel soluble ligands for FGFRs have been identified
      using yeast two-hybrid technology. Overall, the new findings suggest that in
      terms of ligand binding the FGFRs might be an even more promiscuous family of
      receptor tyrosine kinases than was already appreciated.

PMID- 8760338
TI  - DNA elements responsive to auxin.
AB  - Genes induced by the plant hormone auxin are probably involved in the execution
      of vital cellular functions and developmental processes. Experimental approaches
      designed to elucidate the molecular mechanisms of auxin action have focused on
      auxin perception, genetic dissection of the signaling apparatus and specific gene
      activation. Auxin-responsive promoter elements of early genes provide molecular
      tools for probing auxin signaling in reverse. Functional analysis of several
      auxin-specific promoters of unrelated early genes suggests combinatorial
      utilization of both conserved and variable elements. These elements are arranged
      into autonomous domains and the combination of such modules generates uniquely
      composed promoters. Modular promoters allow for auxin-mediated transcriptional
      responses to be revealed in a tissue- and development-specific manner.

PMID- 8760339
TI  - Epithelial integrins.
AB  - The integrin family was originally described as a family of adhesion receptors,
      utilized by cells for attachment to and migration across components of the
      extracellular matrix. Epithelial cells in adult tissues are generally stationary
      cells, but these cells nevertheless express several different integrins. This
      review will discuss the evidence that integrins on epithelial cells are also
      likely to function as signaling molecules, allowing these cells to detect
      attachment or detachment, and changes in the local composition of ligands.
      Signals initiated by integrins appear to modulate epithelial cell
      differentiation, proliferation, survival, and gene expression. Because the local
      concentration of integrin ligands is altered by injury, inflammation, and
      remodeling, signals initiated through integrins are likely to play important
      roles in the responses of epithelial cells to each of these processes.

PMID- 8760340
TI  - Molecular mechanisms of drug inhibition of DNA gyrase.
AB  - DNA gyrase, an enzyme unique to prokaryotes, has been implicated in almost all
      processes that involve DNA. Although efficient inhibitors of this protein have
      been known for more than 20 years, none of them have enjoyed prolonged
      pharmaceutical success. It is only recently that the mechanisms of inhibition for
      some of these classes of drugs have been established unequivocally by X-ray
      crystallography. It is hoped that this detailed structural information will
      assist the design of novel, effective inhibitors of DNA gyrase.

PMID- 8760341
TI  - The neutral theory is dead. Long live the neutral theory.
AB  - The neutral theory of molecular evolution has been instrumental in organizing our
      thinking about the nature of evolutionary forces shaping variation at the DNA
      level. More importantly, it has provided empiricists with a strong set of
      testable predictions and hence, a useful null hypothesis against which to test
      for the presence of selection. Evidence indicates that the neutral theory cannot
      explain key features of protein evolution nor patterns of biased codon usage in
      certain species. Whereas we now have a reasonable model of selection acting on
      synonymous changes in Drosophila, protein evolution remains poorly understood.
      Despite limitations in the applicability of the neutral theory, it is likely to
      remain an integral part of the quest to understand molecular evolution.

PMID- 8760342
TI  - The active role of DNA as a chromatin organizer.
AB  - Histone octamers (hos) and DNA topoisomerase I contribute, along with other
      proteins, to the higher order structure of chromatin. Here we report on the
      similar topological requirements of these two protein model systems for their
      interaction with DNA. Both histone octamers and topoisomerase I positively and
      consistently respond to DNA supercoiling and curvature, and to the spatial
      accessibility of the preferential interaction sites. These findings (1) point to
      the relevance of the topology-related DNA conformation in protein interactions
      and define the particular role of the helically phased rotational information;
      and (2) help to solve the apparent paradoxical behaviour of ubiquitous and
      abundant proteins that interact with defined DNA sites in spite of the lack of
      clear sequence consensuses. Considering firstly, that the interactions with DNA
      of both DNA topoisomerase I and histone octamers are topology-sensitive and that
      upon their interaction the DNA conformation is modified; and secondly, that
      similar behaviours have also been reported for DNA topoisomerase II and histone
      H1, a topology-based functional correlation among all these determinants of the
      higher order structure of chromatin is here suggested.

PMID- 8760343
TI  - Cell cycle regulation in Aspergillus by two protein kinases.
AB  - Great progress has recently been made in our understanding of the regulation of
      the eukaryotic cell cycle, and the central role of cyclin-dependent kinases is
      now clear. In Aspergillus nidulans it has been established that a second class of
      cell-cycle-regulated protein kinases, typified by NIMA (encoded by the nimA
      gene), is also required for cell cycle progression into mitosis. Indeed, both
      p34cdc2/cyclin B and NIMA have to be correctly activated before mitosis can be
      initiated in this species, and p34cdc2/cyclin B plays a role in the mitosis
      specific activation of NIMA. In addition, both kinases have to be proteolytically
      destroyed before mitosis can be completed. NIMA-related kinases may also regulate
      the cell cycle in other eukaryotes, as expression of NIMA can promote mitotic
      events in yeast, frog or human cells. Moreover, dominant-negative versions of
      NIMA can adversely affect the progression of human cells into mitosis, as they do
      in A. nidulans. The ability of NIMA to influence mitotic regulation in human and
      frog cells strongly suggests the existence of a NIMA pathway of mitotic
      regulation in higher eukaryotes. A growing number of NIMA-related kinases have
      been isolated from organisms ranging from fungi to humans, and some of these
      kinases are also cell-cycle-regulated. How NIMA-related kinases and cyclin
      dependent kinases act in concert to promote cell cycle transitions is just
      beginning to be understood. This understanding is the key to a full knowledge of
      cell cycle regulation.

PMID- 8760344
TI  - Inhibition of protein synthesis in frog (Xenopus laevis) egg extracts by an
      antibody against phosphatidylinositol 4,5-bisphosphate.
AB  - The antibody kt10, which is directed against the phospholipid PtdIns(4,5)P2,
      inhibits protein synthesis when added to cytosolic extracts prepared from frog
      eggs. Addition of stable analogues of diacylglycerol and Ins(1,4,5)P3 failed to
      rescue the inhibition of translation, suggesting that the effect of the antibody
      was not to block hydrolysis of PtdIns(4,5)P2. Neomycin, which also binds
      PtdIns(4,5)P2, produced a similar reduction in protein-synthesis levels in the
      extract system, supporting the idea that it is the interaction of the antibody
      with PtdIns(4,5)P2 that is producing the effect.

PMID- 8760345
TI  - Alternative processing of the sarco/endoplasmic reticulum Ca(2+)-ATPase
      transcripts during muscle differentiation is a specifically regulated process.
AB  - Expression of the muscle-specific 2a isoform of the sarco/endoplasmic reticulum
      Ca(2+)-ATPase (SERCA2) requires activation of an otherwise inefficient splice
      process at the 3'-end of the primary gene transcript. We provide evidence that
      SERCA2 splicing is a specifically regulated process, rather than the result of an
      increase in general splice efficiency or a decrease in polyadenylation efficiency
      at the 5'-most polyadenylation site. This is indicated by the fact that changes
      in general splice and polyadenylation efficiency, as observed during B-cell
      maturation, did not affect SERCA2 splicing. Furthermore, expression and
      overexpression studies did not support the hypothesis that changes in the level
      of the alternative splice factor ASF/SF2 or other arginine and serine rich
      proteins are sufficient to obtain the regulation of muscle- and neuronal-specific
      splicing.

PMID- 8760346
TI  - Phosphorylation of phosphoenolpyruvate carboxykinase in plants. Studies in plants
      with C4 photosynthesis and Crassulacean acid metabolism and in germinating seeds.
AB  - We have previously shown that phosphoenolpyruvate carboxykinase (PEPCK) is
      phosphorylated in vivo in the cotyledons of darkened cucumber seedlings and that
      phosphorylation is reversed by light [Walker and Leegood (1995) FEBS Lett. 362,
      70-74]. In this study the molecular mass of PEPCK was estimated in a range of
      gluconeogenic seedlings and in leaves of C4 plants and plants with Crassulacean
      acid metabolism (CAM). Phosphorylation of PEPCK was studied in these plants by
      feeding tissues with [32P]Pi and assessing phosphorylation by SDS/PAGE and
      autoradiography of either total proteins or of immunoprecipitated protein. In
      gluconeogenic seedlings and most CAM plants PEPCK had a molecular mass of 74 kDa,
      whereas in C4 grasses the molecular mass of PEPCK was always smaller and varied
      from 67-71 kDa. In all gluconeogenic seedlings and leaves of CAM plants PEPCK was
      phosphorylated, but it was not phosphorylated in all species of C4 grasses
      studied. In CAM plants, phosphorylation of PEPCK occurred at night and
      dephosphorylation occurred during the day. In C4 grasses phosphorylation occurred
      when leaves were darkened and the enzyme was dephosphorylated following
      illumination, but it was only phosphorylated in those plants with larger (71 kDa)
      molecular mass forms of PEPCK.

PMID- 8760347
TI  - Intracellular dissociation and reassembly of prolyl 4-hydroxylase:the alpha
      subunits associated with the immunoglobulin-heavy-chain binding protein (BiP)
      allowing reassembly with the beta-subunit.
AB  - Prolyl 4-hydroxylase (P4-H) consists of two distinct polypeptides; the
      catalytically more important alpha-subunit and the beta-subunit, which is
      identical to the multifunctional enzyme protein disulphide isomerase. The enzyme
      appears to be assembled in vivo into an alpha 2 beta 2 tetramer from newly
      synthesized alpha-subunits associating with an endogenous pool of beta-subunits.
      Using a cell-free system, we have shown previously that enzyme assembly is redox
      dependent and that assembled alpha-subunits are intramolecularly disulphide
      bonded [John and Bulleid (1994) Biochemistry 33, 14018-14025]. Here we have
      studied this assembly process within intact cells by expressing both subunits in
      COS-1 cells. Newly synthesized alpha-subunits were shown to assemble with the
      beta-subunit, to form insoluble aggregates, or to remain soluble but not
      associate with the beta-subunit. Treatment of cells with dithiothreitol (DTT) led
      to dissociation of P4-H into subunits and on removal of DTT the enzyme
      reassembled. This reassembly was ATP-dependent, suggesting an interaction with an
      ATP-dependent chaperone. This was confirmed when immunoglobulin-heavy-chain
      binding protein (BiP) and alpha-subunits were co-immunoprecipitated with
      antibodies against the alpha-subunit and BiP, respectively. These results
      indicate that unassembled alpha-subunits are maintained in an assembly-competent
      form by interacting with the molecular chaperone BiP.

PMID- 8760348
TI  - Uncoupling effect of polyunsaturated fatty acid deficiency in isolated rat
      hepatocytes:effect on glycerol metabolism.
AB  - The effects of a 4-week deficiency in polyunsaturated fatty acids (PUFA) in
      isolated rat hepatocytes have been investigated for oxidative phosphorylation and
      fatty acid, dihydroxyacetone (DHA) or glycerol metabolism. Oxygen uptake was
      significantly increased (by 20%) with or without fatty acid addition (octanoate
      or oleate) in the PUFA-deficient group compared with controls. The effect
      persisted after oligomycin addition but not after that of potassium cyanide,
      leading to the conclusion that, in these intact cells, the mitochondria were
      uncoupled. The PUFA-deficient group exhibited a significant decrease in the
      cytosolic ATP/ADP ratio, whereas the mitochondrial ratio was not affected. PUFA
      deficiency led to a 16% decrease in DHA metabolism owing to a 34% decrease in
      glycerol kinase activity; the significant decrease in the ATP/ADP ratio was
      accompanied by an increase in the fractional glycolytic flux. In contrast,
      glycerol metabolism was significantly enhanced in the PUFA-deficient group. The
      role of the glycerol 3-phosphate dehydrogenase step in this stimulation was
      evidenced in hepatocytes perifused with glycerol and octanoate in the presence of
      increased concentrations of 2,4-dinitrophenol (Dnp): uncoupling with Dnp led to
      an enhancement of glycerol metabolism, as found in PUFA deficiency, although it
      was more pronounced than in controls. The matrix/cytosol gradients for redox
      potential and ATP/ADP ratio were lower in cells from PUFA-deficient rats,
      suggesting a decreased mitochondrial membrane potential in accordance with the
      uncoupling effect. Moreover, a doubling of the mitochondrial glycerol 3-phosphate
      dehydrogenase activity in the PUFA-deficient group compared with controls led us
      to conclude that the activation of glycerol metabolism is the consequence of two
      mitochondrial effects: uncoupling and an increase in glycerol 3-phosphate
      dehydrogenase activity.

PMID- 8760349
TI  - Calcineurin is essential for DNA synthesis in Swiss 3T3 fibroblasts.
AB  - DNA synthesis was measured 16 h after stimulation of Swiss 3T3 fibroblasts in the
      resting phase with various growth factors (platelet-derived growth factor,
      fibroblast growth factor, lysophosphatidic acid and thrombin). When extracellular
      Ca2+ was chelated by EGTA, or when the influx of Ca2+ from outside to inside the
      cell was blocked by cobalt, DNA synthesis was completely inhibited. As there was
      no effect whatsoever on DNA synthesis when Ca2+ was chelated, or when the influx
      of Ca2+ was blocked up to the first 4 h after growth stimulation, it was
      concluded that, at an early stage, Ca2+ influx from outside to inside the cell is
      not related to the transition from the G1 to the S phase. A Ca2+/calmodulin
      dependent protein kinase II inhibitor (KN-62) had no effect on DNA synthesis.
      However, cyclosporin A and FK-506, which are inhibitors of Ca2+/calmodulin
      dependent protein phosphatase 2B (calcineurin), markedly inhibited DNA synthesis
      stimulated by all of the growth factors. These results indicate that calcineurin
      plays a role, not only in activation of T-cells of the immune system in the
      initial phase, but also in DNA synthesis in fibroblasts. It was concluded that
      Ca2+ influx from outside to inside the cell during the mid-to-late G1 phase,
      followed by calcineurin activation, is essential as a mechanism of growth signal
      transduction.

PMID- 8760350
TI  - Modulation of intrahepatic cholesterol trafficking: evidence by in vivo antisense
      treatment for the involvement of sterol carrier protein-2 in newly synthesized
      cholesterol transport into rat bile.
AB  - Biliary cholesterol represents one of the two major excretory pathways for sterol
      elimination from the body and plays a central role in cholesterol gallstone
      formation. Biliary cholesterol originates from a precursor pool of preformed and
      newly synthesized free cholesterol. Although it has been suggested that newly
      synthesized and preformed biliary cholesterol are secreted by independent
      pathways, the specific cellular and molecular mechanisms are unknown. We used
      male Wistar rats to study the time-course of the appearance of newly synthesized
      cholesterol, phosphatidylcholine and protein into bile. The specific role of
      sterol carrier protein-2 (SCP-2) in the transport of newly synthesized biliary
      cholesterol was evaluated by an in vivo antisense oligonucleotide approach. In
      contrast to [14C]phosphatidylcholine and [35S]proteins, the time-course of
      [14C]cholesterol appearance into bile was rapid, and microtubule- and Golgi
      independent. In vivo SCP-2 antisense treatment reduced and delayed the appearance
      of biliary [14C]cholesterol. Furthermore, hepatic SCP-2 expression increased more
      than 3-fold over control values in rats that had been treated with diosgenin to
      increase biliary secretion of newly synthesized cholesterol. These results
      suggest that SCP-2 is necessary for the rapid transport of newly synthesized
      cholesterol into bile and that hepatocytes can induce SCP-2 expression according
      to the rate of biliary secretion of newly synthesized cholesterol.

PMID- 8760351
TI  - Heat shock selectively inhibits ribosomal RNA gene transcription and down
      regulates E1BF/Ku in mouse lymphosarcoma cells.
AB  - The effect of heat shock on RNA polymerase I (pol I)-directed transcription of
      the rRNA gene was studied in S-100 extract derived from mouse lymphosarcoma
      cells, and by in vivo labelling of rRNA. Exposure of cells to 42 degrees C for 2
      h resulted in complete inhibition of rRNA synthesis in vivo. Pol I transcription
      was inhibited by 50% within 2 h of heat shock and was abolished after 3 h
      exposure at 42 degrees C. Under this condition, the core-promoter-binding
      activity of the factor (CPBF) that modulates pol I transcription was unaffected.
      In contrast, the promoter-binding activity of enhancer-1-binding factor, a
      protein related to the Ku autoantigen, which is involved in pol I transcription
      initiation, was reduced by 50 and 90% after 2 and 3 h of heat shock respectively.
      Western-blot analysis with antibodies specific for the two subunits of Ku protein
      showed the absence of p72 subunit after 3 h of heat shock. Under this condition,
      pol II transcription from the adenovirus major late promoter and pol III
      transcription of 5 S RNA gene remained unaffected. Mixing experiments ruled out
      the possibility that the inhibition of transcription was due to activation of
      nucleases or other inhibitors. This is the first report to show selective down
      regulation of pol I transcription in vitro by heat shock and of the potential
      involvement of a pol I transcription factor in this process.

PMID- 8760352
TI  - Identification of distal silencing elements in the murine interferon-A11 gene
      promoter.
AB  - The murine interferon-A11 (Mu IFN-A11) gene is a member of the IFN-A multigenic
      family. In mouse L929 cells, the weak response of the gene's promoter to viral
      induction is due to a combination of both a point mutation in the virus
      responsive element (VRE) and the presence of negatively regulating sequences
      surrounding the VRE. In the distal part of the promoter, the negatively acting
      E1E2 sequence was delimited. This sequence displays an inhibitory effect in
      either orientation or position on the inducibility of a virus-responsive
      heterologous promoter. It selectively represses VRE-dependent transcription but
      is not able to reduce the transcriptional activity of a VRE-lacking promoter. In
      a transient transfection assay, an E1E2-containing DNA competitor was able to
      derepress the native Mu IFN-A11 promoter. Specific nuclear factors bind to this
      sequence; thus the binding of trans-regulators participates in the repression of
      the Mu IFN-A11 gene. The E1E2 sequence contains an IFN regulatory factor (IRF)
      binding site. Recombinant IRF2 binds this sequence and anti-IRF2 antibodies
      supershift a major complex formed with nuclear extracts. The protein composing
      the complex is 50 kDa in size, indicating the presence of IRF2 or antigenically
      related proteins in the complex. The Mu IFN-A11 gene is the first example within
      the murine IFN-A family, in which a distal promoter element has been identified
      that can negatively modulate the transcriptional response to viral induction.

PMID- 8760353
TI  - Reversal of the temperature-shift-induced growth restriction of a temperature
      sensitive simian virus 40 T-antigen-transformed human fibroblast cell line by
      treatment with retinoic acid.
AB  - We previously established a human fibroblast cell line, HFL 6-2, that contains a
      temperature sensitive simian virus 40 (SV40) T antigen, permitting cell growth at
      35 degrees C but restricting growth at 39 degrees C. p21 (Waf1/Cip1) was
      significantly induced by temperature shifts in HFL 6-2 cells. Here we show that
      all-trans-retinoic acid (RA) treatment prevented the growth restriction of HFL 6
      2 cells at 39 degrees C. In the presence of RA, HFL 6-2 cells proliferated into
      sizeable colonies even at 39 degrees C. [3H]Thymidine incorporation and flow
      cytometry analysis revealed that cells exposed to RA maintained DNA synthesis at
      39 degrees C. Prevention of growth restriction by RA was correlated with a lack
      of induction of p21 at the transcription level. These observations suggest that
      RA may prevent the senescence process by repressing p21 gene expression, and
      perturb the growth regulation of somatic cells.

PMID- 8760354
TI  - Cytokine regulation of glutamate decarboxylase biosynthesis in isolated rat
      islets of Langerhans.
AB  - Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease in which
      cytokines are thought to play an important role in beta-cell destruction and
      immune regulation. A major target of beta-cell autoimmunity in IDDM is the enzyme
      glutamate decarboxylase (GAD). We hypothesized that cytokines in the insulitis
      lesion modulate the synthesis of GAD. This may, in turn, modify the rate of beta
      cell destruction. Accordingly we cultured rat islets in the presence and absence
      of cytokines, and measured synthesis of both isoforms of GAD, GAD65 and GAD67, by
      [35S]methionine incorporation and immunoprecipitation with a rabbit antiserum
      that recognizes both GAD65 and GAD67. Incubation of islets with interleukin (IL)
      1 beta (1 ng/ml, 24 h), tumour necrosis factor alpha (TNF-alpha; 200 units/ml, 24
      h) or interferon gamma (IFN-gamma; 500 units/ml, 72 h) significantly decreased
      the synthesis of both GAD65 and GAD67, but reduced neither total protein
      synthesis nor insulin accumulation in the medium or content. Incubation of islets
      for 24 h in IFN-alpha (1000 units/ml), TNF-beta (50 ng/ml), IL 2 (1000 units/ml),
      IL-4 (100 ng/ml), IL-6 (10 ng/ml), IL-10 (20 ng/ml), IL-12 (10 ng/ml) or
      transforming growth factor beta 2 (TGF-beta 2; 5 ng/ml) did not significantly
      alter GAD65 or GAD67 synthesis. Inhibition of GAD65 and GAD67 protein synthesis
      by IL-1 beta, TNF-alpha or IFN-gamma was reversed by co-incubation with the
      nitric oxide synthase inhibitor, NG-monomethyl arginine (NMMA). Expression of
      both GAD65 and GAD67 mRNA, measured by RNase protection assay, was also decreased
      by IL-1 beta and completely restored to baseline levels by NMMA. Thus the
      synthesis of both isoforms of islet GAD is selectively decreased in the presence
      of IL-1 beta, TNF-alpha or IFN-gamma by a NO-mediated mechanism, probably at the
      level of cytokine gene transcription. As GAD autoimmunity has been previously
      shown to have a pathogenic role in an animal model of IDDM, its inhibition by
      cytokines might limit the immune response, thereby regulating the rate of beta
      cell destruction in IDDM.

PMID- 8760355
TI  - Baculovirus expression of two protein disulphide isomerase isoforms from
      Caenorhabditis elegans and characterization of prolyl 4-hydroxylases containing
      one of these polypeptides as their beta subunit.
AB  - Protein disulphide isomerase (PDI; EC 5.3.4.1) is a multifunctional polypeptide
      that is identical to the beta subunit of prolyl 4-hydroxylases. We report here on
      the cloning and expression of the Caenorhabditis elegans PDI/beta polypeptide and
      its isoform. The overall amino acid sequence identity and similarity between the
      processed human and C. elegans PDI/beta polypeptides are 61% and 85%
      respectively, and those between the C. elegans PDI/beta polypeptide and the PDI
      isoform 46% and 73%. The isoform differs from the PDI/beta and ERp60 polypeptides
      in that its N-terminal thioredoxin-like domain has an unusual catalytic site
      sequence -CVHC-. Expression studies in insect cells demonstrated that the C.
      elegans PDI/beta polypeptide forms an active prolyl 4-hydroxylase alpha 2 beta 2
      tetramer with the human alpha subunit and an alpha beta dimer with the C. elegans
      alpha subunit, whereas the C. elegans PDI isoform formed no prolyl 4-hydroxylase
      with either alpha subunit. Removal of the 32-residue C-terminal extension from
      the C. elegans alpha subunit totally eliminated alpha beta dimer formation. The
      C. elegans PDI/beta polypeptide formed less prolyl 4-hydroxylase with both the
      human and C. elegans alpha subunits than did the human PDI/beta polypeptide,
      being particularly ineffective with the C. elegans alpha subunit. Experiments
      with hybrid polypeptides in which the C-terminal regions had been exchanged
      between the human and C. elegans PDI/beta polypeptides indicated that differences
      in the C-terminal region are one reason, but not the only one, for the
      differences in prolyl 4-hydroxylase formation between the human and C. elegans
      PDI/beta polypeptides. The catalytic properties of the C. elegans prolyl 4
      hydroxylase alpha beta dimer were very similar to those of the vertebrate type II
      prolyl 4-hydroxylase tetramer, including the K(m) for the hydroxylation of long
      polypeptide substrates.

PMID- 8760356
TI  - Identification of the cysteine residues implicated in the formation of alpha 2
      and alpha/beta dimers of rat meprin.
AB  - Meprin (endopeptidase-24.18; EC 3.4.24.18) is a multisubunit zinc
      metallopeptidase found in the brush-border membranes of rodent kidney and human
      intestine. The alpha and beta subunits of meprin are disulphide-linked to form
      either soluble alpha 2 homodimers or membrane-associated alpha/beta heterodimers.
      The aim of the present study was to identify the cysteine residue(s) implicated
      in the formation of alpha 2 and alpha/beta dimers and to investigate the effects
      of dimerization on intracellular transport and processing of the alpha subunit.
      Three cysteine residue candidates for the formation of disulphide bonds in the
      alpha subunit were selected by hydrophobic cluster analysis. These residues,
      located at positions 309, 560 and 562, were mutated to serine residues. When the
      resulting alpha subunit mutants were expressed alone in COS-1 cells, the alpha
      C560S and alpha C562S mutants were found to be secreted as alpha 2 homodimers
      whereas the alpha C309S mutant was found as monomers in the culture medium. In
      double-transfection experiments with the wild-type beta subunit, the alpha C560S
      and alpha C562S mutants behaved exactly as the wild-type alpha subunit and formed
      membrane-bound alpha/beta heterodimers. In contrast, the alpha C309S mutant was
      not retained at the cell surface but rather secreted as monomers in the culture
      medium, as was found in the simple transfection experiment. These results show
      that, despite the normal expression level and folding of the protein in a
      transport-competent from, the alpha C309S mutant is unable to form alpha 2
      homodimers or alpha/beta heterodimers. This suggests that Cys309 is the unique
      residue of the alpha subunit implicated in the alpha 2 and alpha/beta
      dimerizations. Hydrophobic cluster analysis of the alpha and beta subunit
      sequences predicts that Cys309 is similar to Cys306 of the beta subunit. We
      mutated the latter residue to a serine and expressed the beta C306S mutant and
      the wild-type alpha subunit in the same COS-1 cells. No beta 2 or alpha/beta
      dimers were observed on immunoblotting, showing that Cys306 of the beta subunit
      is required for the formation of intermolecular disulphide bonds both in beta 2
      homodimers and in alpha/beta heterodimers. Taken together, these results suggest
      that the alpha/beta heterodimeric form of meprin is held together by a single
      disulphide bond linking Cys309 in the alpha subunit to Cys306 in the beta
      subunit.

PMID- 8760357
TI  - Endothelial-cell-stimulating angiogenesis factor (ESAF) activates progelatinase A
      (72 kDa type IV collagenase), prostromelysin 1 and procollagenase and reactivates
      their complexes with tissue inhibitors of metalloproteinases: a role for ESAF in
      non-inflammatory angiogenesis.
AB  - Endothelial-cell-stimulating angiogenesis factor (ESAF) has been shown to
      activate procollagenase and reactivate complexes of collagenase and gelatinase A
      with tissue inhibitor of metallo-proteinase (TIMP)-1. In the present paper we
      show a purification protocol for bovine pineal ESAF and that purified ESAF
      activates progelatinase A and prostromelysin-1. Unlike the activation of
      procollagenase by plasmin/plasminogen activator, which requires the presence of
      stromelysin for full activation, ESAF is able to activate fully all three
      proenzymes. Purified ESAF is also shown to reactivate the complexes of gelatinase
      A, collagenase and stromelysin-1 with TIMP-2. Once separated, both enzyme and
      inhibitor are active; however, ESAF binds to the enzyme in a manner preventing it
      from further inhibition by TIMP. ESAF is the only physiological molecule able to
      reactivate the TIMP/enzyme complex.

PMID- 8760358
TI  - Protection by chlorpromazine, albumin and bivalent cations against haemolysis
      induced by melittin, [Ala-14]melittin and whole bee venom.
AB  - The ability of the peptides melittin, [Ala-14]melittin (P14A) and whole bee venom
      to lyse red blood cells (RBC) and to cause shape transformation, binding,
      partitioning and changes in volume of the cells during haemolysis, as well as the
      action of the bivalent cations Zn2+ and Ca2+, chlorpromazine, albumin and plasma
      on the peptide-induced haemolysis of RBC in high ionic-strength solution, have
      been investigated. The protective effect of all inhibitors depends on whether
      they have been added to the media before or after the cells. When added before
      the cells they reduced significantly the rate of peptide-induced haemolysis and
      shape transformation. The effect was maximal when agents acted simultaneously
      after introduction of the cells into the media containing both inhibitors and
      peptides. Incubation of the cells in isotonic solution before the addition of
      peptides enhanced 2-3-fold the RBC susceptibility (i.e. rate of haemolysis) to
      lytic action of the same amount of peptides, and increased the order of the
      haemolytic reaction, although the power law coefficient did not exceed a value of
      2 for all peptides, suggesting that haemolysis is attributable to the monomeric
      or dimeric forms of the peptides. Partition coefficients were of the order of
      approximately 10(6) M-1, and P14A possessed a value 3-fold larger compared with
      melittin and bee venom, which correlated with its enhanced haemolytic activity.
      The protective action of inhibitors against peptide-induced haemolysis has been
      explained on the basis of their ability to compete with peptide binding at an
      early stage of peptide-membrane interaction, and not as a result of inhibition of
      a pre-existing peptide-induced pore. Whereas melittin increased the volume of RBC
      during haemolysis, P14A, melittin in the presence of phospholipase A2 or bee
      venom, reduced the volume in a concentration-dependent manner. The present data
      reveal the significant role of the initial stage of peptide-membrane interaction
      and peptide structure in the mechanism of haemolysis. These data are not
      consistent with a lipid-based mechanism of peptide-induced haemolysis, indicating
      that the mode of peptide-protein interaction is an important and decisive step in
      the haemolytic mechanism. It should be noted that data (in the form of three
      additional Tables) on the ability of inhibitors to protect cells from haemolysis
      when inhibitor and peptide act simultaneously are available. They are reported in
      Supplementary Publication SUP 50178, which has been deposited at the British
      Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ,
      U.K., from whom copies can be obtained on the terms indicated in Biochem. J.
      (1996) 313, 9.

PMID- 8760359
TI  - The properties of a subtype of the inositol 1,4,5-trisphosphate receptor
      resulting from alternative splicing of the mRNA in the ligand-binding domain.
AB  - Subtypes of the type-1 inositol 1,4,5-trisphosphate (InsP3) receptor differ at
      the mRNA level in two small variably spliced segments. One segment (SI) encodes
      for a sequence within the InsP3-binding domain, thus its presence or absence
      could affect the functions of the receptor. We have used anti-peptide antibodies
      to confirm the existence of different subtypes of the InsP3 receptor (InsP3R)
      protein. The antibody against residues 322-332, within the SI region, recognized
      a 260 kDa polypeptide in membranes prepared from rat cerebellum or cerebral
      cortex. The cerebellum contained a few percent of the InsP3R protein having the
      SI region, whereas the cerebral cortex contained a high proportion of receptors
      with the SI region. These two tissues were representative of both isoforms, SI-
      or SI+, and displayed the same [3H]InsP3-binding characteristics. Thus, the SI
      region was not involved in the basic properties of the receptor. Deletion of the
      peptide 316-352 containing the SI segment greatly reduced InsP3 binding
      [Miyawaki, Furuichi, Ryou, Yoshikawa, Nakagawa, Saitoh and Mikoshiba (1991) Proc.
      Natl. Acad. Sci. U.S.A. 88, 4911-4915]. The antibodies against the SI region or
      against residues 337-349 did not modify the binding of [3H]InsP3 in the cortical
      membranes rich in the SI+ isoform or in cerebellar membranes. These results
      suggested that the SI region was not part of the binding site. The subcellular
      distribution of these two isoforms was then investigated in rat liver. The two
      isoforms were identified in different membrane fractions and they followed the
      same subcellular distribution. We suggest that the domain with the SI region may
      be involved in a function other than InsP3-induced Ca2+ release.

PMID- 8760360
TI  - Cytokeratin 8 released by breast carcinoma cells in vitro binds plasminogen and
      tissue-type plasminogen activator and promotes plasminogen activation.
AB  - Cell-surface activation of plasminogen may be important in diseases that involve
      cellular migration, including atherosclerosis and tumour invasion/metastasis.
      Cytokeratin 8 (CK 8) has been identified as a plasminogen-binding protein
      expressed on the external surfaces of hepatocytes and breast carcinoma cells
      [Hembrough, Vasudevan, Allietta, Glass and Gonias (1995) J. Cell Sci. 108, 1071
      1082]. In this investigation, we demonstrate that a soluble form of CK 8 is
      released into the culture medium of breast cancer cell lines. The released CK 8
      is in the form of variably sized polymers that bind plasminogen and promote the
      activation of [Glu1]plasminogen and [Lys78]plasminogen by single-chain tissue
      type plasminogen activator (sct-PA). To assess the mechanism by which CK 8
      promotes plasminogen activation, CK 8 was purified from rat hepatocytes and
      immobilized in microtitre plates. Immobilized CK 8 bound 125I-plasminogen and
      125I-sct-PA in a specific and saturable manner. The KDs were 160 +/- 40 nM and
      250 +/- 48 nM, respectively. Activation of plasminogen bound to immobilized CK 8
      was accelerated compared with plasminogen in solution, as determined using a
      coupled-substrate fluorescence assay and SDS/PAGE. The ability of CK 8 to promote
      plasminogen activation may be important in the pericellular spaces surrounding
      breast cancer cells and at the cell surface.

PMID- 8760361
TI  - Identification of the transcription factors NF-YA and NF-YB as factors A and B
      that bound to the promoter of the major histocompatibility complex class II gene
      I-A beta.
AB  - The Y box is a conserved sequence in the promoter of major histocompatibility
      complex (MHC) class II genes, which contains a CCAAT sequence (CCAAT box).
      Previously, we partially purified the DNA-binding protein that recognizes the Y
      box of the I-A beta gene and showed that it consisted of two components (factors
      A and B) both of which were necessary for optimal DNA binding. The genes for the
      heteromeric protein NF-Y (NF-YA and NF-YB), which binds to the I-E alpha Y box
      have been cloned. We subsequently isolated the genes for NF-YA and NF-YB using
      oligonucleotides designed from the published sequences. NF-YA and NF-YB were
      tested for binding to the I-A beta and I-E alpha Y boxes. While neither NF-YA or
      NF-YB alone bound to the Y box, when the components were mixed the complex bound
      to the I-A beta Y box with high affinity. Moreover, NF-YA and NF-YB could be
      complemented for binding to DNA by factor B or factor A, respectively. These
      results suggest that the active binding protein is NF-YA in factor A extracts and
      NF-YB in factor B extracts. Finally, antibodies against NF-YA and NF-YB were
      shown to induce a supershift when nuclear extracts were added to the double
      stranded oligodeoxynucleotide covering the Y box of the I-A beta gene. Antisense
      expression constructs of both NF-YA and NF-YB were made and their effect on
      expression from the I-A beta promoter was tested. Either antisense construction,
      when transfected into cells, lowered the expression of a reporter gene linked to
      the I-A beta promoter. This study provides direct evidence of the identification
      of NF-YA and NF-YB as the previously described factors A and B. Moreover, these
      results strongly implicate NF-Y in the expression of the MHC class II gene I-A
      beta.

PMID- 8760362
TI  - Amplification of the thapsigargin-evoked increase in the cytosolic free Ca2+
      concentration by acetylcholine in acutely isolated mouse submandibular acinar
      cells.
AB  - The intracellular Ca2+ concentration was measured in single, acutely isolated,
      mouse submandibular acinar cells loaded with fura-2 AM. All experiments were
      performed in the absence of extracellular Ca2+ in order to eliminate Ca2+ influx.
      The microsomal ATPase inhibitor, thapsigargin, was used to release Ca2+ from
      intracellular stores and simultaneously prevent re-uptake into the stores.
      Sequential application of thapsigargin (2 microM) and the Ca2+ ionophore
      ionomycin (500 nM) indicated that thapsigargin was able to mobilize practically
      all intracellular Ca2+. Furthermore, in comparison with results obtained
      following inhibition of the plasma membrane Ca(2+)-ATPase by La3+ (2 mM), it may
      be shown that slowly unloading the intracellular Ca2+ stores using thapsigargin
      does not normally cause a massive, cytotoxic, increase in the cytosolic Ca2+
      concentration, because Ca2+ is rapidly extruded from the cell across the plasma
      membrane. Application of a submaximal dose of acetylcholine (500 nM) during the
      rising phase of the response to thapsigargin caused a 3-4-fold increase in the
      amplitude of the rise in the cytosolic Ca2+ concentration without any significant
      alteration of the time course of the response. As thapsigargin alone is capable
      of mobilizing all releasable Ca2+, this increase in amplitude is most likely the
      result of inhibition of the Ca2+ extrusion process by acetylcholine.

PMID- 8760364
TI  - Flux control exerted by mitochondrial outer membrane carnitine
      palmitoyltransferase over beta-oxidation, ketogenesis and tricarboxylic acid
      cycle activity in hepatocytes isolated from rats in different metabolic states.
AB  - The Flux Control Coefficients of mitochondrial outer membrane carnitine
      palmitoyltransferase (CPT I) with respect to the overall rates of beta-oxidation,
      ketogenesis and tricarboxylic acid cycle activity were measured in hepatocytes
      isolated from rats in different metabolic states (fed, 24 h-starved, starved
      refed and starved/insulin-treated). These conditions were chosen because there is
      controversy as to whether, when significant control ceases to be exerted by CPT I
      over the rate of fatty oxidation [Moir and Zammit (1994) Trends Biochem. Sci. 19,
      313-317], this is transferred to one or more steps proximal to acylcarnitine
      synthesis (e.g. decreased delivery of fatty acids to the liver) or to the
      reaction catalysed by mitochondrial 3-hydroxy-3-methyl-glutaryl-CoA synthase
      [Hegardt (1995) Biochem. Soc. Trans. 23, 486-490]. Therefore isolated hepatocytes
      were used in the present study to exclude the involvement of changes in the rate
      of delivery of non-esterified fatty acids (NEFA) to the liver, such as occur in
      vivo, and to ascertain whether, under conditions of constant supply of NEFA, CPT
      I retains control over the relevant fluxes of fatty acid oxidation to ketones and
      carbon dioxide, or whether control is transferred to another (intrahepatocytic)
      site. The results clearly show that the Flux Control Coefficients of CPT I with
      respect to overall beta-oxidation and ketogenesis are very high under all
      conditions investigated, indicating that control is not lost to another
      intrahepatic site during the metabolic transitions studied. The control of CPT I
      over tricarboxylic acid cycle activity was always very low. The significance of
      these findings for the integration of fatty acid and carbohydrate metabolism in
      the liver is discussed.

PMID- 8760363
TI  - Differential expression of fibromodulin mRNA associated with tendon fibril
      growth: isolation and characterization of a chicken fibromodulin cDNA.
AB  - A 450 bp cDNA fragment similar to that encoding bovine fibromodulin was isolated
      using a screening procedure to isolate genes differentially expressed between the
      pre- and post-growth phases of fibril growth in the developing chicken embryo
      metatarsal tendon. Using this fragment, a 2.4 kb cDNA clone for chicken
      fibromodulin was isolated from a lambda ZAP library, and the 5' rapid
      amplification of cDNA ends technique was employed to clone the 5'end of the
      fibromodulin cDNA. The full-length cDNA contained an open reading frame coding
      for a 380-amino-acid protein. There was approximately 80% similarity with human,
      rat and bovine fibromodulins, which confirmed its identity as fibromodulin.
      Structural features of the deduced sequence include an 18-amino-acid signal
      peptide, cysteine residues in conserved positions in the N- and C-terminal
      regions, and a central leucine-rich domain containing eleven repeats of the
      sequence LXXLXLXXNXL/I. Features unique to chicken fibromodulin include an
      additional glycosylation site as well as a decreased number of tyrosine residues
      that could be sulphated, and therefore potential changes in the charge of the
      molecule. In addition, there was little similarity among the untranslated
      regions. When compared with chicken decorin and lumican, fibromodulin showed
      greater similarity to the other keratan sulphate-containing proteoglycan,
      lumican. Northern blot analysis revealed a 6-8-fold increase in the fibromodulin
      mRNA level from day 14 to day 19 of development. In the chicken tendon, collagen
      fibril growth is a process characterized by a precipitous increase in length
      during a short developmental period. The necessary changes would require the
      expression of different genes regulating fibril formation and growth, and
      interactions between fibromodulin and collagen fibrils may participate in the
      regulation of collagen fibril growth and matrix assembly.

PMID- 8760365
TI  - Mechanism of the reaction catalysed by cytosolic 5'
      nucleotidase/phosphotransferase: formation of a phosphorylated intermediate.
AB  - Cytosolic 5'-nucleotidase preferentially catalysing the hydrolysis of IMP, GMP
      and their deoxy derivatives, and endowed with phosphotransferase activity, was
      purified from calf thymus and its reaction mechanism was studied. In the presence
      of [32P]IMP, ATP and MgCl2, a covalent enzyme-phosphate intermediate was trapped
      by mixing with an SDS solution. Heart or acid treatment of the enzyme before
      incubation with radiolabelled substrate prevented formation of the intermediate.
      Furthermore, on the basis of studies on the kinetic parameters of the enzyme as
      function of pH, and of experiments on thiol oxidation and photo-oxidation, we
      suggest the involvement of cysteine and histidine residue(s) in the reaction
      mechanism.

PMID- 8760366
TI  - Lack of integrin alpha-chain endoproteolytic cleavage in furin-deficient human
      colon adenocarcinoma cells LoVo.
AB  - In the present report the biosynthesis of the integrin alpha-chains endowed with
      constitutive endoproteolytic cleavage was evaluated in LoVo cells where furin, a
      subtilisin-like convertase involved in post-translational endoproteolytic
      processing, is not functional. It was found that cell-surface alpha 3, alpha 6
      and alpha v subunits were not processed endoproteolytically into heavy and light
      chains as they were in HT29-D4 cells, a furin-competent cell line. Complete
      removal of N-linked oligosaccharides and pulse-chase experiments confirmed that
      the cleavage of the alpha 6 integrin subunit occurring 45 min after translation
      in HT29 cells did not take place in LoVo cells. Apart from cleavage deficiency,
      alpha 6 subunit glycosylation, association with beta 4 subunits and targeting to
      the plasma membrane seemed comparable in LoVo and HT29 cells. The pro-alpha 6 and
      the pro-alpha 3 subunits immunopurified from LoVo cells were highly sensitive to
      endoproteolysis by recombinant furin. Furin cleavage was calcium dependent and
      resulted in the conversion of the 140 kDa pro-alpha 6 into a 120 kDa heavy chain.
      These results suggest strongly that furin is involved in the endoproteolytic
      processing of cleavable integrin alpha subunits.

PMID- 8760367
TI  - Overproduction of stable ornithine decarboxylase and antizyme in the
      difluoromethylornithine-resistant cell line DH23b.
AB  - DH23b cells, a variant of the HTC line selected for their resistance to
      difluoromethylornithine, exhibit defective feedback regulation of ornithine
      decarboxylase (ODC) stability and polyamine transport, and accumulate ODC protein
      to > 1000 times normal concentrations. The components of the polyamine feedback
      regulation system have been examined in an attempt to understand these unusual
      responses. Southern-blot analysis revealed an amplification (approx. 10-fold) in
      ODC DNA sequence without any concomitant increase in antizyme. Moreover, the
      amplified ODC sequence contains a single base substitution that results in the
      conversion of Cys-441 into Trp. This modification has previously been shown to
      cause ODC stability in HMOA cells. Although antizyme activity has not been noted
      in DH23b cells, Western-blot analysis revealed the accumulation of antizyme
      protein to > 50 times that induced in parental HTC cells. This increase is
      consistent with a 6-9-fold increase in the half-life of antizyme in these cells,
      a consequence of the inability of the mutant ODC-antizyme complex to be degraded
      by 26 S proteasome. Associated with the stabilization of antizyme in both DH23b
      and HMOA cells is the appearance of two additional forms of antizyme protein with
      apparent molecular masses of 22 and 18.5 kDa. It is suggested that these result
      from proteolytic removal of discrete fragments from the N-terminal end of
      antizyme, perhaps an indication of an initial step in rapid antizyme turnover.

PMID- 8760368
TI  - Immunological characterization of eristostatin and echistatin binding sites on
      alpha IIb beta 3 and alpha V beta 3 integrins.
AB  - Two disintegrins with a high degree of amino acid sequence similarity, echistatin
      and eristostatin, showed a low level of interaction with Chinese hamster ovary
      (CHO) cells, but they bound to CHO cells transfected with alpha IIb beta 3 genes
      (A5 cells) and to CHO cells transfected with alpha v beta 3 genes (VNRC3 cells)
      in a reversible and saturable manner. Scatchard analysis revealed that
      eristostatin bound to 816000 sites per A5 cell (Kd 28 nM) and to 200000 sites (Kd
      14 nM) per VNRC3 cell respectively. However, VNRC3 cells did not bind to
      immobilized eristostatin. Echistatin bound to 495000 sites (Kd 53 nM) per A5 cell
      and to 443000 sites (Kd 20 nM) per VNRC3 cell. As determined by flow cytometry,
      radiobinding assay and adhesion studies, binding of both disintegrins to A5 cells
      and resting platelets and binding of echistatin to VNRC3 cells resulted in the
      expression of ligand-induced binding sites (LIBS) on the beta 3 subunit.
      Eristostatin inhibited, more strongly than echistatin, the binding of three
      monoclonal antibodies: OPG2 (RGD motif dependent), A2A9 (alpha IIb beta 3 complex
      dependent) and 7E3 (alpha IIb beta 3 and alpha v beta 3 complex dependent) to A5
      cells, to resting and to activated platelets and to purified alpha IIb beta 3.
      Experiments in which echistatin and eristostatin were used alone or in
      combination to inhibit the binding of 7E3 and OPG2 antibodies to resting
      platelets suggested that these two disintegrins bind to different but overlapping
      sites on alpha IIb beta 3 integrin. Monoclonal antibody LM 609 and echistatin
      seemed to bind to different sites on alpha v beta 3 integrin. However, echistatin
      inhibited binding of 7E3 antibody to VNRC3 cells and to purified alpha v beta 3
      suggesting that alpha v beta 3 and alpha IIb beta 3 might share the same epitope
      to which both echistatin and 7E3 bind. Eristostatin had no effect in these
      systems, providing further evidence that it binds to a different epitope on alpha
      v beta 3.

PMID- 8760369
TI  - In vitro and in vivo induction of brown adipocyte uncoupling protein
      (thermogenin) by retinoic acid.
AB  - The effects of retinoic acid (RA) isomers (all-trans-RA and 9-cis-RA) on the
      appearance of uncoupling protein (UCP; thermogenin), the only unequivocal
      molecular marker of the brown adipocyte differentiated phenotype, have been
      investigated in primary cultures of brown adipocytes, in the brown adipocyte cell
      line HIB 1B and directly in intact mice. The results obtained with cultured cells
      indicate that retinoids function as inducers of the appearance of UCP and, at the
      same time, partially inhibit brown adipocyte cell proliferation. The two RA
      isomers displayed similar effectiveness as UCP inducers, their effect being
      comparable with that triggered by noradrenaline, so far considered to be the main
      modulator of UCP gene expression. The effectiveness of retinoids as UCP inducers
      was dependent on the stage of brown adipocyte differentiation, being maximal in
      confluent primary cells and in the medium-late differentiation stage of HIB 1B
      cells. Corroborating the results obtained in vitro, we show that administration
      of all-trans-RA or 9-cis-RA to mice leads to an increase in their brown adipose
      tissue specific UCP content. 9-cis-RA treatment also prevented the loss of UCP on
      cold deacclimation. To our knowledge, this is the first report of a stimulatory
      effect of retinoid compounds on UCP induction in vivo.

PMID- 8760370
TI  - Nucleoside uptake in rat liver parenchymal cells.
AB  - Rat liver parenchymal cells express Na(+)-dependent and Na(+)- independent
      nucleoside transport activity. The Na(+)-dependent component shows kinetic
      properties and substrate specificity similar to those reported for plasma
      membrane vesicles [Ruiz-Montasell, Casado, Felipe and Pastor-Anglada (1992) J.
      Membr. Biol. 128, 227-233]. This transport activity shows apparent K(m) values
      for uridine in the range 8-13 microM and a Vmax of 246 pmol of uridine per 3 min
      per 10(5) cells. Most nucleosides, including the analogue formycin B, cis-inhibit
      Na(+)-dependent uridine transport, although thymidine and cytidine are poor
      inhibitors. Inosine and adenosine inhibit Na(+)-dependent uridine uptake in a
      dose-dependent manner, reaching total inhibition. Guanosine also inhibits Na(+)
      dependent uridine uptake, although there is some residual transport activity (35%
      of the control values) that is resistant to high concentrations of guanosine but
      may be inhibited by low concentrations of adenosine. The transport activity that
      is inhibited by high concentrations of thymidine is similar to the guanosine
      resistant fraction. These observations are consistent with the presence of at
      least two Na(+)-dependent transport systems. Na(+)-dependent uridine uptake is
      sensitive to N-ethylmaleimide treatment, but Na(+)-independent transport is not.
      Nitrobenzylthioinosine (NBTI) stimulates Na(+)-dependent uridine uptake. The NBTI
      effect involves a change in Vmax, it is rapid, dose-dependent, does not need
      preincubation and can be abolished by depleting the Na+ transmembrane
      electrochemical gradient. Na(+)-independent uridine transport seems to be
      insensitive to NBTI. Under the same experimental conditions, NBTI effectively
      blocks most of the Na(+)-independent uridine uptake in hepatoma cells. Thus the
      stimulatory effect of NBTI on the concentrative nucleoside transporter of liver
      parenchymal cells cannot be explained by inhibition of nucleoside efflux.

PMID- 8760371
TI  - Hypoxanthine enters human vascular endothelial cells (ECV 304) via the
      nitrobenzylthioinosine-insensitive equilibrative nucleoside transporter.
AB  - The transport properties of the nucleobase hypoxanthine were examined in the
      human umbilical vein endothelial cell line ECV 304. Initial rates of hypoxanthine
      influx were independent of extracellular cations: replacement of Na+ with Li+,
      Rb+, N-methyl-D-glucamine or choline had no significant effect on hypoxanthine
      uptake by ECV 304 cells. Kinetic analysis demonstrated the presence of a single
      saturable system for the transport of hypoxanthine in ECV 304 cells with an
      apparent K(m) of 320 +/- 10 microM and a Vmax of 5.6 +/- 0.9 pmol/10(6) cells per
      s. Hypoxanthine uptake was inhibited by the nucleosides adenosine, uridine and
      thymidine (apparent Ki 41 +/- 6, 240 +/- 27 and 59 +/- 8 microM respectively) and
      the nucleoside transport inhibitors nitrobenzylthioinosine (NBMPR), dilazep and
      dipyridamole (apparent Ki 2.5 +/- 0.3, 11 +/- 3 and 0.16 +/- 0.006 microM
      respectively), whereas the nucleobases adenine, guanine and thymine had little
      effect (50% inhibition at > 1 mM). ECV 304 cells were also shown to transport
      adenosine via both the NBMPR-sensitive and -insensitive nucleoside carriers.
      Hypoxanthine specifically inhibited adenosine transport via the NBMPR-insensitive
      system in a competitive manner (apparent Ki 290 +/- 14 microM). These results
      indicate that hypoxanthine entry into ECV 304 endothelial cells is mediated by
      the NBMPR-insensitive nucleoside carrier present in these cells.

PMID- 8760372
TI  - Kinetics of the non-specific calcium leak from non-mitochondrial calcium stores
      in permeabilized A7r5 cells.
AB  - We have investigated the detailed kinetics of the passive Ca2+ leak from non
      mitochondrial Ca2+ stores in permeabilized A7r5 cells. The decrease in the
      content of stored Ca2+ in the presence of 2 microM thapsigargin deviated from a
      single-exponential curve in the initial phase of the efflux. The deviation
      persisted after correcting this efflux for passively bound Ca2+. The non-single
      exponential nature of the spontaneous release also occurred when the initial
      store Ca2+ content was reduced to 40% of its original value by pretreatment with
      200 nM inositol 1,4,5-trisphosphate (InsP3). The passive Ca2+ leak could be
      modelled by two exponential curves with discrete rate constants of 0.06 min-1 and
      0.98 min-1, and not by any other type of non-exponential decay. We concluded that
      individual store units are heterogeneous with respect to their passive Ca2+
      permeability. This non-exponential nature of the passive Ca2+ release is
      unrelated to the non-single-exponential InsP3-induced Ca2+ release.

PMID- 8760373
TI  - Antibiotic interactions with the hammerhead ribozyme:tetracyclines as a new class
      of hammerhead inhibitor.
AB  - A screening of a range of common laboratory antibiotics for inhibition of the
      hammerhead ribozyme has shown that in addition to certain aminoglycosides (most
      notably neomycin B) the tetracyclines are also effective inhibitors, with
      chlorotetracycline being more effective than tetracycline. Inhibition by
      chlorotetracycline is not as strong as that by neomycin B but is more
      complicated, with at least two binding sites apparent. As with hammerhead
      inhibition by neomycin B, chlorotetracycline inhibition can be overcome by
      raising the concentration of the Mg2+ ion cofactor. We find that around six Mg2+
      ions will displace neomycin B, compared with twelve for chlorotetracycline.
      Inhibition observed in the presence of mixtures of neomycin B and
      chlorotetracycline is consistent with separate binding sites on the hammerhead
      for these two classes of antibiotic. Under certain conditions of the mixing order
      and low concentration of chlorotetracycline, enhancement of single-turnover
      hammerhead cleavage by up to 20% is observed, with higher concentrations of
      antibiotic being inhibitory. We have also found that the presence of 2.5% (v/v)
      DMSO causes a 30% enhancement of the single-turnover cleavage. These results thus
      extend the range of known inhibitors of hammerhead cleavage, and also demonstrate
      how the cleavage can be accelerated.

PMID- 8760374
TI  - Enzyme-to-enzyme channelling of Krebs cycle metabolic intermediates in Caco-2
      cells exposed to [2-13c]propionate.
AB  - The generation of 13C-labelled lactate by colon carcinoma cells of the Caco-2
      line incubated for 120 min in the presence of [2-13C]propionate (10 mM) was
      assessed by 13C NMR. About 10% of the total amount of 13C-labelled lactate was
      recovered in the cell pellet and displayed a [2-13C]lactate/[3-13C]lactate
      isotopomer ratio of 1.18 +/- 0.01. An even higher isotopomer ratio of 1.53 +/-
      0.14 was observed in the case of 13C-labelled lactate released by the cells into
      the incubation medium. These findings indicate that, in the Caco-2 cells,
      metabolic intermediates of the Krebs cycle undergo enzyme-to-enzyme channelling
      in the sequence of reactions catalysed by succinyl-CoA synthetase, succinate
      dehydrogenase and fumarase.

PMID- 8760375
TI  - Calcium-dependent ADP-ribosylation of high-mobility-group I (HMGI) proteins.
AB  - Micrococcal nuclease digestion of nuclei from mouse Lewis lung carcinoma cells
      releases a protein mixture into the supernatant that lacks histone H1 and
      contains a full complement of high-mobility-group I (HMGI) proteins (i.e. I, Y
      and I-C). This implies that all three HMGI proteins are localized at the nuclease
      sensitive regions of active chromatin. It is also shown that if Ca2+ ions are
      present in the nuclear incubation buffer (with or without exogenous nuclease),
      all three HMGI proteins become ADP-ribosylated. We propose that this modification
      of HMGI family proteins is part of the general poly(ADP-ribosyl)ation that
      accompanies DNA damage in apoptosis and other processes.

PMID- 8760376
TI  - Structural domains of heparan sulphate for specific recognition of the C-terminal
      heparin-binding domain of human plasma fibronectin (HEPII).
AB  - Heparan sulphate (HS) is an abundant polysaccharide component of the pericellular
      domain and is found in most soft tissues and all adherent cells in culture. It
      interacts with a wide spectrum of proteins including polypeptide growth factors
      and glycoproteins of the extracellular matrix. These interactions might influence
      fundamental cellular activities such as adhesion, growth and migration. HS might
      therefore represent a highly adaptive mechanism by which cells respond to their
      environment. The present study shows that the interaction between fibroblast HS,
      metabolically labelled with [3H]glucosamine, and the C-terminal heparin-binding
      domain of human plasma fibronectin (HEPII), is determined by distinct regions of
      the polysaccharide chain. By using a very sensitive affinity-chromatography
      method and specific polysaccharide scission it was shown that the HEPII-binding
      regions of HS reside within sulphated domains that are resistant to degradation
      by heparinase III. In addition, optimal binding was achieved with specific
      heparinase III-resistant fragments of 14-16 monosaccharides in length. The
      affinity of HS for HEPII was significantly decreased when the polysaccharide was
      cleaved with heparinase I. Chondroitin sulphate and dermatan sulphate were poor
      competitive inhibitors of [3H]HS binding to HEPII whereas unlabelled HS and
      heparin gave a strong inhibitory activity, with heparin being the most potent
      inhibitor. These findings suggest that the interaction between HEPII and HS is
      specific and requires extended sequences of seven to eight N-sulphated
      disaccharides in which a proportion of the iduronate residues are sulphated at C
      2. The results have important implications for the functions of HS in cell
      adhesion and migration.

PMID- 8760377
TI  - Characterization of pig liver glutathione S-transferases using HPLC-electrospray
      ionization mass spectrometry.
AB  - We have characterized 11 porcine liver cytosolic glutathione S-transferase (GST)
      subunits from their precise molecular mass, immunoreactivity and partial amino
      acid sequence. Four Alpha-, six Mu- and one unexpected Pi-class GST subunits were
      found with average molecular masses of 24.984-25.228 kDa, 25.039-25.657 kDa and
      23.510 kDa respectively. Molecular masses were established using electrospray
      ionization mass spectrometry, with a precision of +/- 3-4 mass units. Glutathione
      (GSH) and S-hexylglutathione (ShGSH) were tested as affinity ligands in the
      purification procedure. The binding selectivity of GSH was better than that of
      ShGSH, although non-GST proteins were retained on both matrices. As already
      described in other studies, a number of non-GST proteins bound to the affinity
      resins. Two of them were tentatively identified as mevalonate kinase and carbonyl
      reductase. The characterization of pig liver cytosolic GST subunits pattern
      achieved in this work should constitute a useful tool for rapid evaluation of
      these enzymes' expression in modulation studies.

PMID- 8760378
TI  - Role of an aprotinin-sensitive protease in the activation of Ca(2+)-ATPase by
      superoxide radical (O2-.) in microsomes of pulmonary vascular smooth muscle.
AB  - We have investigated the role of an aprotinin-sensitive protease in regulating
      Ca(2+)-ATPase activity and Ca2+ uptake (ATP-dependent and Na(+)-dependent) in
      microsomes of bovine pulmonary vascular smooth muscle during treatment with the
      O2(-.)-generating system hypoxanthine plus xanthine oxidase. Treatment of the
      smooth muscle microsomes with the O2(-.)-generating system produced a protease in
      a gelatin-containing zymogram with an apparent molecular mass of 16 kDa. This 16
      kDa proteolytic protein was found to be inhibited by superoxide dismutase (SOD)
      and aprotinin but not by PMSF. Using polyclonal antiserum to aprotinin, we found
      that it is an ambient antiprotease of the smooth muscle microsomes. Treatment of
      the microsomes with the O2(-.)-generating system stimulated protease activity
      tested with a synthetic substrate N-benzoyl-DL-arginine p-nitroanilide and also
      enhanced Ca(2+)-ATPase activity. It also stimulated ATP-dependent Ca2+ uptake. In
      contrast, Na(+)-dependent Ca2+ uptake was found to be inhibited by the O2(-.)
      generating system. Pretreatment of the microsomes with SOD and aprotinin
      preserved the increase in protease activity, Ca(2+)-ATPase activity and ATP
      dependent Ca2+ uptake. In addition, O2(-.)-caused inhibition of the Na(+)
      dependent Ca2+ uptake which was reversed by SOD and aprotinin. Pretreatment with
      PMSF did not cause any discernible alteration in the protease activity, Ca(2+)
      ATPase activity. ATP-dependent Ca2+ uptake and Na(+)-dependent Ca2+ uptake in the
      microsomes caused by the O2(-.)-generating system. These results suggest that an
      aprotinin-sensitive protease plays a pivotal role in regulating Ca(2+)-ATPase and
      Ca(2+)-uptake activities in microsomes of pulmonary vascular smooth muscle under
      oxidant O2(-.)-triggered conditions.

PMID- 8760379
TI  - Purification of a rat neurotensin receptor expressed in Escherichia coli.
AB  - A truncated rat neurotensin receptor (NTR), expressed in Escherichia coli with
      the maltose-binding protein fused to its N-terminus and the 13 amino acid Bio tag
      fused to its C-terminus, was purified to apparent homogeneity in two steps by use
      of the monomeric avidin system followed by a novel neurotensin column. This
      purification protocol was developed by engineering a variety of affinity tags on
      to the C-terminus of NTR. Surprisingly, expression levels varied considerably
      depending on the C-terminal tag used. Functional expression of NTR was highest
      (800 receptors/cell) when thioredoxin was placed between the receptor C-terminus
      and the tag, indicating a stabilizing effect of the thioredoxin moiety. Several
      affinity chromatography methods were tested for purification. NTR with the in
      vivo-biotinylated Bio tag was purified with the highest efficiency compared with
      NTR with the Strep tag or a hexa-histidine tail. Co-expression of biotin ligase
      improved considerably the in vivo biotinylation of the Bio tag and, therefore,
      the overall purification yield. Proteolysis of the NTR fusion protein was
      prevented by removing a protease-sensitive site discovered at the N-terminus of
      NTR. The ligand binding properties of the purified receptor were similar to those
      of the membrane-bound protein and the native receptor. The scale-up of this
      purification scheme, to provide sufficient protein for biophysical studies, is in
      progress.

PMID- 8760380
TI  - pH-dependent hysteretic behaviour of human myeloblastin (leucocyte proteinase 3).
AB  - Human myeloblastin (leucocyte proteinase 3) showed a very slow approach to the
      steady-state velocity when the pH was rapidly increased from 3.2 to 7.0. The
      kinetic mechanism of this hysteretic process was interpreted as a slow
      conformational change of myeloblastin from an inactive form at acidic pH to the
      active form at neutral pH. The transition between the two enzyme forms could
      occur spontaneously in the absence of substrates with a first-order rate constant
      of 0.0033 s-1. In the presence of peptide substrates activation occurred more
      rapidly: the observed rate constant was linearly dependent upon the substrate
      concentration and contained a contribution of the spontaneous as well as of the
      substrate-dependent process, whose second-order rate constant was characteristic
      of the particular substrate. This pH-dependent phenomenon of hysteresis on the
      part of myeloblastin, that is not manifested by the closely related leucocyte
      elastase, may have a physiological control function during phagocytosis by
      damping the rate of interconversion between enzymically inactive and active
      enzyme conformations.

PMID- 8760381
TI  - Inhibition of liver RNA breakdown during acute inflammation in the rat.
AB  - Liver RNA- and protein-degradation rates were measured after the induction of
      acute inflammation in the rat. A preliminary study determined changes in hepatic
      RNA and protein content 12, 18 and 24 h after a turpentine oil injection. The RNA
      content in turpentine-treated rats compared with pair-fed animals increased
      significantly and sharply from 12 h (+ 11%) to 18 h (+ 32%) and slightly
      thereafter (+ 37% at 24 h). The liver protein content was significantly enhanced
      only at 24 h (+ 11%) in response to inflammation. RNA-degradation rates were
      determined in livers perfused cyclically in situ for 15 min by measuring the
      accumulation of radioactive cytidine in the medium 60 h after in vivo labelling
      of RNA by [5-3H]cytidine instead of [6-14C]orotic acid, the most commonly used
      radioactive marker. Several validation procedures showed that the method employed
      was a valid alternative to the use of radioactive orotic acid. RNA-degradation
      rates, which mainly reflect rRNA breakdown, were significantly lower in the
      turpentine-treated rats than in respective pair-fed animals at 18 and 24 h (57
      and 45% decrease respectively). Proteolysis rates measured at 24 h together with
      RNA breakdown by valine accumulation in the perfusion medium were not modified
      after turpentine treatment. The main factors known to regulate RNA degradation
      (amino acids, insulin/glucagon ratio) were measured in the portal blood 24 h
      after induction of acute inflammation. Of the known regulatory amino acids, only
      glutamine and to a lesser extent methionine were increased in the turpentine
      treated rats as compared with their pair-fed counterparts. The insulin/glucagon
      molar ratio was similar in both groups. In conclusion, the reduced breakdown of
      RNA, especially rRNA, is largely responsible for the accumulation of hepatic RNA
      during acute inflammation. This inhibition of RNA degradation could possibly be
      related to the increase in glutamine.

PMID- 8760382
TI  - Regulation of adenine nucleotide translocase and glycerol 3-phosphate
      dehydrogenase expression by thyroid hormones in different rat tissues.
AB  - Thyroid hormone (T3)-dependent gene expression of the adenine nucleotide
      translocase (ANT) and the FAD-linked glycerol 3-phosphate dehydrogenase (mGPDH)
      was investigated in several rat tissues. Both proteins provide an important link
      between cytosolic and mitochondrial metabolic pathways and seem to be involved in
      the stimulation of mitochondrial oxygen consumption in response to T3. Here we
      show that two ANT isoforms are expressed in rat, the muscle-specific ANT1 form
      and the ubiquitous ANT2 form. The expression of ANT1 mRNA is not sensitive to T3
      whereas the amount of ANT2 mRNA is increased 7-9-fold in liver and heart within
      12-48 h after T3 application. Little or no effect of T3 on ANT2 mRNA was observed
      in kidney and brain. The mRNA changes are paralleled by an increase in ANT
      protein, thus explaining the accelerated ADP/ATP exchange observed in
      mitochondria isolated from hyperthyroid rats. The key role of ANT2 in the control
      of hyperthyroid metabolism is evident because the expression of the mersalyl
      sensitive phosphate carrier and the mitochondrial creatine kinase mRNA, which are
      functionally linked to ANT, did not respond to T3. Similarly to the ADP/ATP
      exchange, the transfer of cytosolic NADH to the respiratory chain via the
      glycerophosphate shuttle is very sensitive to T3. Recently we demonstrated the 10
      15-fold induction of mGPDH mRNA in rat liver after administration of T3 [Muller
      and Seitz (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 10581-10585]. Here we show
      that, in contrast with ANT2, the time course of induction is fast (4-6 h).
      Furthermore, mGPDH mRNA is induced 6-fold by T3 in heart and 4-fold in kidney.
      From these results we conclude that the T3-mediated transcriptional induction
      leading to increased activity of ANT2 and mGPDH contributes considerably to the
      increase in mitochondrial oxygen consumption in rat tissues.

PMID- 8760384
TI  - Regulation of beta-adrenoceptor density and mRNA levels in the rat heart cell
      line H9c2.
AB  - The regulation of the expression of beta-adrenoceptor (beta-ARs) is not
      thoroughly understood. We demonstrate that the rat heart cell-line H9c2 expresses
      both beta 1- and beta 2-ARs. In radioligand-binding experiments, the maximal
      binding capacity of (-)-[125I]-iodocyanopindolol was determined as 18 +/- 0.6
      fmol/mg of protein with a KD of 35.4 +/- 4.1 pM. Competitive radioligand-binding
      experiments with subtype-specific beta-antagonists reveal a subtype ratio of beta
      1- to beta 2-ARs of 29%: 71%. With competitive reverse-transcriptase PCR we found
      beta 2-mRNA to be up to 1600 times more frequent than beta 1-mRNA. Treatment of
      the H9c2 cell-line with the beta-adrenergic agonist (-)-isoproterenol (10(-6) M),
      the antagonist (-)-propranolol (10(-6) M) and the glucocorticoid dexamethasone
      (500 nM) induces regulatory effects on both the beta-AR protein and mRNA level.
      Isoproterenol treatment leads to down-regulation of the total receptor number by
      56 +/- 4%, due to a decrease in beta 2-ARs, while maintaining the beta 1-AR
      number constant. On the transcription level, both beta 1-and beta 2-mRNAs are
      decreased by 30% and 42% respectively. mRNA stability measurements reveal a
      reduced half-life of beta 2-mRNA from 9.3 h to 6.5 h after isoproterenol
      treatment. Incubation of cells with (-)-propranolol does not affect the amounts
      of beta-ARs and their mRNAs. Dexamethasone induces a 1.8 +/- 0.2-fold increase in
      beta-AR number over the basal level as well as a 1.9 +/- 0.2-fold increase in the
      amount of beta 2-mRNA. Because the half-life of beta 2-mRNA was unaffected by
      dexamethasone, the increased beta 2-mRNA level must be due to an enhanced
      transcription rate. The beta 1-mRNA levels are unchanged during dexamethasone
      incubation of the cells. Our data clearly demonstrate that treatment of H9c2 rat
      heart cells with isoproterenol and dexamethasone induces alterations in the level
      of RNA stability as well as gene transcription, leading to altered receptor
      numbers.

PMID- 8760383
TI  - Interactions between cytosolic components of the NADPH oxidase: p40phox interacts
      with both p67phox and p47phox.
AB  - The NADPH oxidase of neutrophils and other bone-marrow-derived phagocytic cells
      is a multi-component system consisting of a flavocytochrome b in the plasma
      membrane and at least four cytosolic proteins. Three of the cytosolic proteins
      contain src homology 3 (SH3) domains, two each in p47phox and p67phox, and one in
      p40phox. All three translocate from the cytosol to the flavocytochrome in the
      membrane upon stimulation of the cells. A small G-protein, p21rac, is also
      involved in activation of the oxidase. The three cytosolic phox proteins occur as
      a complex in the cytosol and the strongest interaction appeared to be between
      p67phox and p40phox. We have investigated the interaction between p40phox and the
      other two cytosolic phox proteins by in vitro binding assays. An affinity-bead
      approach was used as well as a biosensor technique (surface plasmon resonance).
      We observed the strongest attachment between p40phox and p67phox where the
      binding was between the N-terminal half of p67phox and the C-terminal half of
      p40phox, and did not appear to involve SH3 domains and proline-rich sequences.
      p40phox also bound p47phox but more weakly than it did p67phox.

PMID- 8760385
TI  - Phosphatidylethanol stimulates the plasma-membrane calcium pump from human
      erythrocytes.
AB  - Phosphatidylethanol is formed by "transphosphatidylation' of phospholipids with
      ethanol catalysed by phospholipase D and can be accumulated in the plasma
      membrane of mammalian cells after treatment of animals with ethanol. In the
      present work we show that phosphatidylalcohols, such as phosphatidylethanol and
      phosphatidylbutanol, produced a twofold stimulation of the Ca(2+)-ATPase activity
      of human erythrocytes. This stimulation occurs with the purified, solubilized
      enzyme as well as with ghost preparations, where the enzyme is in its natural
      lipidic environment and is different to that obtained with other acidic
      phospholipids such as phosphatidylserine. Addition of either phosphatidylserine,
      phosphatidylethanol or phosphatidylbutanol to the purified Ca(2+)-ATPase, or to
      ghosts preparations, increased the affinity of the enzyme for Ca2+ and the
      maximal velocity of the reaction as compared with controls in the absence of
      acidic phospholipids. However, in contrast with what occurs with
      phosphatidylserine, simultaneous addition of phosphatidyl-alcohols and calmodulin
      increased the affinity of the enzyme for Ca2+ to a greater extent than each added
      separately. When ethanol was added to either the purified erythrocyte Ca(2+)
      ATPase or to erythrocyte-ghost preparations in the presence of acidic
      phospholipids, an additive effect was observed. There was an increase in the
      affinity for Ca2+ and in the maximal velocity of the reaction, well above the
      values obtained with ethanol or with the acidic phospholipids tested separately.
      These findings could have pharmacological importance. It is conceivable that the
      decrease in the intracellular Ca(2+) concentration that has been reported in
      erythrocytes as a result of ethanol intoxication could be due to the stimulation
      of the Ca(2+)-ATPase by the accumulated phosphatidylethanol, to a direct effect
      of ethanol on the enzyme or to an additive combination of both.

PMID- 8760386
TI  - Human surfactant protein A with two distinct oligomeric structures which exhibit
      different capacities to interact with alveolar type II cells.
AB  - The lung lavage fluids from patients with pulmonary alveolar proteinosis have
      been generally used as a source for human surfactant protein A (SP-A). We have
      recently found that a multimerized form of SP-A oligomer (alveolar proteinosis
      protein-I, APP-I) exists besides the normal-sized octadecamer (APP-II) in SP-As
      isolated from the patients. When analysed by Bio-Gel A15m column chromatography
      in 5 mM Tris buffer (pH 7.4), the apparent molecular masses of APP-I and APP-II
      were 1.65 MDa and 0.93 MDa, respectively. Gel-filtration analysis also revealed
      that APP-II is clearly separated from APP-I in the presence of 2 mM Ca2+ and 150
      mM NaCI. We investigated the abilities of both SP-A oligomers to regulate
      phospholipid secretion and to bind to alveolar type II cells. Although APP-I
      inhibited lipid secretion, it was clearly a less effective inhibitor than APP-II.
      IC50 for inhibition of lipid secretion was apparently 0.23 +/- 0.08 microgram/ml
      (0.14 +/- 0.05 nM) and 0.055 +/- 0.019 microgram/ml (0.059 +/- 0.020 nM) for APP
      I and APP-II, respectively. Both proteins bound to monolayers of type II cells in
      a concentration-dependent manner; however, APP-I clearly had a lower affinity to
      bind to type II cells. The apparent dissociation contants were, K(d) = 2.31 +/-
      0.70 microgram/ml (1.40 +/- 0.43 nM) and 0.89 +/- 0.22 microgram/ml (0.95 +/-
      0.24 nM) for APP-I and APP-II, respectively. Excess unlabelled rat SP-A replaced
      45% of 125I-APP-I and 77% of 125I-APP-II for type II cell binding. Although 125I
      APP-II competed with excess unlabelled APP-I or APP-II, 125I-APP-I failed to
      compete and instead its binding rather increased in the presence of unlabelled
      APPs. The biotinylated APP-I bound to APP-I and APP-II coated on to microtitre
      wells in a concentration-dependent manner, indicating that APP-I interacts with
      APPs. This study demonstrates that the multimerized form of human SP-A oligomer
      exhibits the following attributes: (1) the reduced capacity to regulate
      phospholipid secretion from type II cells, and (2) lower affinity to bind to type
      II cells, and that the integrity of a flower-bouquet-like octadecameric structure
      of SP-A oligomer is important for the expression of full activity of this
      protein, indicating the importance of the oligomeric structure of mammalian
      lectins with collagenous domains.

PMID- 8760388
TI  - Oil-bodies from sunflower (Helianthus annuus L.) seeds.

PMID- 8760389
TI  - Oleosins and oil bodies in plant seeds have postulated structures.

PMID- 8760390
TI  - In vitro studies of the genotoxic effects of bitumen and coal-tar fume
      condensates: comparison of data obtained by mutagenicity testing and DNA adduct
      analysis by 32P-postlabelling.
AB  - Bitumens contain traces of polycyclic aromatic compounds (PACs), a part of which
      will end up in the fumes emitted during hot handling of bitumen-containing
      products, e.g. during roadpaving. Although exposure of workers to these fumes is
      low, it might lead to health problems. Studies on bitumen fume condensates (BFCs)
      showed weak to moderate mutagenic activities, but studies on DNA adduct formation
      have not been reported. Therefore, a study was initiated in which fumes were
      generated from two road grade bitumens, in such a way that they were
      representative of the fumes produced in the field. The combined
      vapour/particulates were tested in vitro for their ability to produce DNA adducts
      and in modified Ames mutation assays, using a number of different strains. An
      attempt was made to relate the results to chemical data, such as the content of a
      number of individual polycyclic aromatic hydrocarbons (PAHs) and with a measure
      for the total PAC content. As a reference material fume condensate from coal-tar
      (coal-tar pitch volatiles; CTPV) were subjected to the same tests. All fume
      condensates tested were mutagenic to all strains and induced the formation of DNA
      adducts. The patterns of DNA adducts, obtained by 32P-postlabelling, arising from
      the BFCs were qualitatively different from the patterns of adducts obtained from
      the CTPVs, implying qualitative differences in the nature of the compounds
      responsible for the formation of these adducts. This is corroborated by the
      observation that for BFCs quantitative adduct levels are higher than would be
      expected based on the PAH content. These data thus indicate that the PAHs
      analysed are not the sole components responsible for adduct formation from BFCs,
      but that an important contribution comes from other (hetero- and/or substituted-)
      PACs.

PMID- 8760387
TI  - Insulin-responsive tissues contain the core complex protein SNAP-25 (synaptosomal
      associated protein 25) A and B isoforms in addition to syntaxin 4 and
      synaptobrevins 1 and 2.
AB  - SNAP-25 (synaptosomal-associated protein 25), syntaxin and synaptobrevin are the
      three SNARE [soluble NSF attachment protein receptor (where NSF = N
      ethylmaleimide-sensitive fusion protein)] proteins that form the core complex
      involved in synaptic vesicle docking and subsequent fusion with the target
      membrane. The present study is aimed at understanding the mechanisms of fusion of
      vesicles carrying glucose transporter proteins with the plasma membrane in human
      insulin-responsive tissues. It describes the isolation and characterization of
      cDNA molecules encoding SNAP-25 A and B isoforms, syntaxin 4 and synaptobrevins
      (also known as vehicle-associated membrane proteins) from two major human insulin
      responsive tissues, skeletal muscle and fat. The DNA and deduced amino acid
      sequences of SNAP-25 revealed perfect identity with the previously reported human
      neural SNAP-25 A and B isoforms. Our results indicate the presence of both
      isoforms both in insulin-responsive tissues and in in vitro cultured 3T3-L1
      cells, but suggest a differential pattern of gene expression: isoform A is the
      major species in adipose tissue, and isoform B is the major species in skeletal
      muscle. The presence of SNAP-25 protein in 3T3-L1 cells was demonstrated by
      immunofluorescence microscopy using an anti-SNAP-25 monoclonal antibody.
      Immunoprecipitation experiments using the same monoclonal antibody also revealed
      the presence of SNAP-25 protein in plasma membrane fractions from rat epididymal
      fat pads. The syntaxin 4-encoding region from skeletal muscle contains five
      nucleotide differences from the previously reported placental cDNA sequence, two
      of which result in amino acid changes: Asp-174 to Glu and Val-269 to Ala. The
      synaptobrevin 1 cDNA from skeletal muscle contains two nucleotide differences
      when compared with the corresponding clone from neural tissues, one of which is
      silent and the other resulting in the amino acid change Thr-102 to Ala. The cDNA
      sequence of the protein from fat is identical with that of human synaptobrevin 1
      from neural tissues. Furthermore, we have confirmed the presence of syntaxin 4 in
      fat and of synaptobrevin 2 in skeletal muscle by PCR amplification and Southern
      hybridization analysis. Using the yeast two-hybrid system, an interaction was
      observed between the full-length cytoplasmic domains of syntaxin 4 and
      synaptobrevin 2, a vesicle membrane SNARE previously shown by others to be
      associated with vesicles carrying the GLUT4 glucose transporter protein, but no
      interaction was seen with synaptobrevin 1. Flow cytometry of low-density
      microsomes isolated from fat cells was used to demonstrate the binding of
      syntaxin 4 to a subset of vesicles carrying GLUT4 protein; whereas SNAP-25 on its
      own bound poorly to these vesicles, the syntaxin 4-SNAP-25 complex gave a strong
      interaction.

PMID- 8760391
TI  - Reactivity of the one-electron reduction product from nifedipine with relevant
      biological targets.
AB  - The reactivity of the electrochemically generated nitro radical anion from
      nifedipine, a nitro aryl 1,4-dihydropyridine derivative, with relevant
      endobiotics and thiol-containing xenobiotics, was quantitatively assessed by
      cyclic voltammetry. The method was based on the decrease in the return-to-forward
      peak current ratio after the addition of compounds. A quantitative procedure to
      calculate the respective interaction constants between the radicals and the
      xeno/endobiotics is also provided. In the optimal selected conditions, i.e. mixed
      media (0.015 M aqueous citrate/DMF: 40/60, 0.3 M KCl, 0.1 TBAI) at pH 9.0 the
      following order of reactivity was obtained: glutathione > uracil > adenine and
      cysteamine > N-acetylcysteine > captopril > penicillamine. In all cases, the
      interaction rate constants for these derivatives were greater than the natural
      decay constant of the radical. Studies on the reactivity at pH 7.4 were also
      conducted. Results from these experiments indicate a significant reactivity
      between the radical and the endo/xenobiotics. The increase in the stability of
      the radical anion by increasing the pH of the mixed media resulted in a decreased
      reaction with the endo/xenobiotics tested. Computerized simulation with DIGISIM
      2.0 of the proposed mechanisms fitted very well with the experimental results for
      both the natural decay of the radical and its reaction with the tested compounds.

PMID- 8760393
TI  - Vesiculation induced by amphiphiles and ionophore A23187 in porcine platelets: a
      transmission electron microscopic study.
AB  - Amphiphiles, known to induce exo- and endovesiculation in human erythrocytes,
      were studied by means of transmission electron microscopy (TEM) for their ability
      to induce shedding of vesicles (microparticles) from the porcine platelet plasma
      membrane. While echinocytogenic amphiphiles induced shedding of vesicles to the
      extracellular medium (exovesiculation), stomatocytogenic amphiphiles did not
      induce endovesiculation. The rapid (< 1 min) formation of many thin spicules in
      platelets upon treatment with echinocytogenic amphiphiles, indicates that spicule
      formation is caused by a primary interaction of the amphiphile with the plasma
      membrane. Agonist- (Ca(2+)-ionophore A23187, thrombin and collagen) induced shape
      changes, however, seem to involve contractile cytoskeletal processes since
      treated cells attained heavily irregular shapes with broad pseudopods. Our study
      indicates that the mechanisms involved in amphiphile- and agonist-induced
      exovesiculation differ. Amphiphile-induced exovesicles are mainly electron-dense
      spherical structures (phi 150-200 nm) which originate from the formed spicules.
      Ionophore A23187-induced exovesicles are large (phi 200-800 nm) predominantly
      electron-lucent structures which are mainly shed from the cell body and seem to
      originate from extrusions of the canalicular system. Our study shows that there
      are several similarities but also obvious differences in the response of
      platelets and erythrocytes to amphiphile-treatment.

PMID- 8760392
TI  - Evaluation of the cytotoxic mechanism mediated by baccatin III, the synthetic
      precursor of taxol.
AB  - Baccatin III, which is used as a precursor for the semisynthesis of taxol, showed
      cytotoxic activity against a variety of cancer cell lines in culture, with ED50
      values ranging from approximately 8 to 50 microM. Although the potency of this
      response is much lower than that mediated by taxol, it was interesting to note
      that any significant cytotoxic response could be mediated by this compound. Thus,
      it was considered of potential value to investigate the mechanism of cytotoxic
      action. Consistent with an antimitotic mode of action, baccatin III induced
      cultured cells to accumulate in the G2 + M phases of the cell cycle. However,
      unlike taxol, which potentiates the polymerization of tubulin, baccatin III
      mediated an antimitotic response through inhibition of the polymerization
      reaction, similar to colchicine, podophyllotoxin, or vinblastine. Accordingly,
      baccatin III was unable to reduce the extent of Ca(2+)-induced depolymerization,
      a hallmark of the biological response mediated by taxol. To further explore the
      mode of antimitotic activity facilitated by baccatin III, competitive
      interactions with the colchicine, podophyllotoxin, and vinblastine binding sites
      of tubulin were investigated. Baccatin III displaced the binding of radiolabeled
      colchicine or radiolabeled podophyllotoxin, but did not displaced the binding of
      radiolabeled vinblastine. Greater affinity with the colchicine binding site was
      observed and the kinetics of inhibition were shown to be mixed. The side chain of
      taxol, which differentiates the molecule from baccatin III and is known to be of
      requisite importance for the unique activity mediated by taxol, is not by itself
      active in any of these processes. Thus, the baccatin III nucleus of taxol may
      lead to an interaction with tubulin through traditional binding sites.
      Facilitated by this interaction, the intact molecule of taxol may thereby be
      permitted to potentiate tubulin polymerization and block cells in the mitotic
      phase of the cell cycle.

PMID- 8760394
TI  - Aromatic DNA adducts in lymphocytes of humans working at high and low traffic
      density areas.
AB  - Aromatic DNA adduct levels were determined by the 32P-postlabelling assay in
      lymphocytes isolated from newspaper vendors working at urban high traffic areas
      (n = 31) and suburban low traffic areas (n = 22) in Milan, Italy. The DNA adduct
      levels ranged from 0.7 to 6.7/10(8) nucleotides, while most of them were between
      1.0 and 3.0/10(8) nucleotides. No difference was found between the DNA adduct
      levels of the high-exposed group (2.2/10(8) and the low-exposed group (2.2/10(8).
      The heavy smokers (n = 8) had 23% higher DNA adduct level (2.7/10(8)) than the
      non-smokers (n = 37, 2.2/10(8) (P = 0.27), but no correlation was found between
      the adduct level and the number of cigarettes/day. Analysis of variance of the
      DNA adduct levels among the 14 pairs of individuals working at the same news
      stands revealed little effect of the environmental air exposure on the DNA adduct
      level.

PMID- 8760395
TI  - Hibiscus protocatechuic acid protects against oxidative damage induced by tert
      butylhydroperoxide in rat primary hepatocytes.
AB  - Hibiscus protocatechuic acid (PCA), a simple phenolic compound isolated from
      Hibiscus sabdariffa L., was studied for its protective effects against oxidative
      damage induced by tert-butylhydroperoxide (t-BHP) in a primary culture of rat
      hepatocytes. It had been reported that exposure of isolated hepatocytes to t-BHP
      results in leakage of lactate dehydrogenase (LDH) and alanine transaminase (ALT),
      peroxidation of cellular lipids, and depolarization of mitochondria. The present
      investigations showed that PCA at concentrations of 0.05 mg/ml and 0.10 mg/ml
      significantly decreased the leakage of LDH (P < 0.01) and ALT (P < 0.05 and P <
      0.01) and the formation of malondialdehyde (MDA; P < 0.05 and P < 0.01) induced
      by 30-min treatment with t-BHP (1.5 mM) in primary cultured rat hepatocytes. PCA
      also attenuated t-BHP (0.10 mM) induced mitochondrial depolarization as
      determined by a retention test of rhodamine 123 and DNA repair synthesis as
      evidenced by unscheduled DNA synthesis (UDS). In addition, PCA exhibited an
      effective ability to quench 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH). In
      conclusion, PCA demonstrated protective effects against cytotoxicity and
      genotoxicity of hepatocytes induced by t-BHP. One of mechanisms of PCA's
      protective effect may be associated with its property of scavenging free
      radicals.

PMID- 8760396
TI  - 8-Arylguanine adducts from arenediazonium ions and DNA.
AB  - Arenediazonium ions (ArN2+) are genotoxic though the source of their genotoxicity
      is unknown. The present studies were undertaken to determine if reductive
      decomposition of ArN2+ to aryl radicals (Ar) in the presence of calf thymus DNA
      (ctDNA) or in cells results in the formation of DNA adducts. We found that when
      arenediazonium ions of the general structure p-X-ArN2+ (X = CH3, CH2OCH3, CH2OH)
      are allowed to react with ctDNA or incubated with cells under conditions that
      produce p-X-Ar, DNA adducts are formed with guanine. The structure of the adduct
      is the C8-substitution product derived from guanine and p-X-Ar. Formation of p-X
      Ar was determined by ESR spin-trapping with 5,5-dimethyl-1-pyrroline N-oxide
      (DMPO). The extent of C8-arylguanine adduction was measured by high performance
      liquid chromatography (HPLC) analysis of the DNA hydrosylate and comparison with
      authentic synthetic standards. The C8-arylguanine adducts observed to form may be
      important in regard to the genotoxicity of ArN2+, though other DNA adducts such
      as the N6-triazene of adenine or C8-aryladenine adducts can form. Finally, though
      the formation of C8-arylguanine adducts from arenediazonium ions has been
      proposed, this is the first report demonstrating their formation in DNA.

PMID- 8760398
TI  - A case of abnormal sex-dimorphism for bristle number in Drosophila melanogaster.
AB  - A line of Drosophila melanogaster with average male sternopleural bristle number
      higher than that of females was obtained after many generations of disruptive
      selection, where males with high bristle score were mated to females with low
      scores. This abnormal sex-dimorphism did not influence other bristle traits. Dose
      compensation mechanisms were not involved, and by means of chromosome
      substitutions it could be shown that both X-linked and autosomal loci contributed
      to the sex-dimorphism.

PMID- 8760397
TI  - Limited genetic differentiation among wild Oryctolagus cuniculus L. (rabbit)
      populations in arid eastern Australia.
AB  - A systems approach is necessary for effective control of feral rabbit
      (Oryctolagus cuniculus L.) populations in the arid environments of Australia.
      Localized control procedures may result in local extinctions, but the persistence
      of the overall population will depend on the probability of recolonization, and
      hence, the degree of isolation of each local population unit. Genetic markers
      obtained using allozyme electrophoresis, temperature gradient gel electrophoresis
      (TGGE) and heteroduplex analysis (HA) were used to characterize the degree of
      structuring and extent of gene flow among rabbit populations in arid Queensland,
      Australia. Allozyme allele frequency data showed that there was no significant
      differentiation among sites (average FST = 0.005) and no isolation-by-distance or
      environmental discontinuity effects. TGGE/HA results also revealed no significant
      differentiation in mitochondrial DNA Control Region haplotype frequencies among
      sites and low interpopulation nucleotide divergence estimates (NST = 0.013).
      Therefore, rabbit populations exhibited a high degree of gene flow over large
      geographical areas (1600 km2) and were essentially a single panmictic unit.
      Unpredictable environmental conditions together with the spatial configuration of
      habitats which possess different probabilities of extinction may have resulted in
      repeated local extinctions followed by recolonization and homogenizing gene flow.
      These data suggest that current rabbit control strategies based on individual
      warren management may not achieve effective control in arid Queensland.

PMID- 8760399
TI  - Male-killing bacterium in a fifth ladybird beetle, Coleomegilla maculata
      (Coleoptera:Coccinellidae).
AB  - Inherited symbionts which selectively cause the death of male hosts are found
      widely across the Insecta. Previous studies have shown a single, but different
      micro-organism to be responsible for male-killing in each taxonomic group
      studied. We here produce evidence that within a group of insects, the
      Coccinellidae, there is more than one causal agent of male lethality. We report a
      novel observation of a male-killing trait in the species Coleomegilla maculata.
      Six of 26 crosses were found to produce a female-biased sex ratio associated with
      a low egg hatch-rate. The trait was matrilinearly inherited and was observed to
      be tetracycline-sensitive. However, tests which indicate the presence of a
      Rickettsia, previously found to cause male-killing in another member of the
      Coccinellidae, Adalia bipunctata, proved negative. We therefore conclude that the
      phenomenon of male-killing is multicausal, within, as well as between, taxonomic
      groups of the Insecta.

PMID- 8760400
TI  - On the presence of DNA polymerase alpha in human lymphocyte nuclei and
      chromosomes.
AB  - Experiments were carried out to correlate the cytological localization of DNA
      polymerase alpha with the presence of its specific mRNA in human lymphocytes
      studied at different times after phytohaemagglutinin stimulation. Our data
      indicated that in resting cells it is not possible to detect DNA polymerase alpha
      protein or mRNA by Northern hybridization. By contrast, in stimulated cells the
      detection of mRNA specific for DNA polymerase alpha synthesis is possible after
      16 h phytohaemagglutin stimulation, whereas immunolocalization is possible after
      only 4 h stimulation. Observation of cytological preparations from cells
      stimulated for times long enough to obtain mitoses surprisingly showed an intense
      immunoreaction in mitotic chromosomes treated with monoclonal antibodies to DNA
      polymerase alpha.

PMID- 8760401
TI  - Genetic differentiation of Anopheles gambiae populations from East and west
      Africa: comparison of microsatellite and allozyme loci.
AB  - Genetic variation of Anopheles gambiae was analysed to assess interpopulation
      divergence over a 6000 km distance using short tandem repeat (microsatellite)
      loci and allozyme loci. Differentiation of populations from Kenya and Senegal
      measured by allele length variation at five microsatellite loci was compared with
      estimates calculated from published data on six allozyme loci (Miles, 1978). The
      average Wright's FST of microsatellite loci (0.016) was lower than that of
      allozymes (0.036). Slatkin's RST values for microsatellite loci were generally
      higher than their FST values, but the average RST value was virtually identical
      (0.036) to the average allozyme FST. These low estimates of differentiation
      correspond to an effective migration index (Nm) larger than 3, suggesting that
      gene flow across the continent is only weakly restricted. Polymorphism of
      microsatellite loci was significantly higher than that of allozymes, probably
      because the former experience considerably higher mutation rates. That
      microsatellite loci did not measure greater interpopulation divergence than
      allozyme loci suggested constraints on microsatellite evolution. Alternatively,
      extensive mosquito dispersal, aided by human transportation during the last
      century, better explains the low differentiation and the similarity of estimates
      derived from both types of genetic markers.

PMID- 8760402
TI  - Number of lethal equivalents in human populations: how good are the previous
      estimates?
AB  - Lee et al. (1996) recently developed a method for interval estimation of the
      number of lethal equivalents by using a hierarchical structure of likelihood
      functions. This hierarchical model consists of two multinomial trials: one of the
      sampling process of the parents from the population of interest, and the other
      for the survival of the offspring of the families obtained by mating the parents.
      The method, initially developed for selfing and full-sib mating, is extended here
      to include more general mating systems as well as mixtures of mating systems. We
      applied it to human data sets for which confidence intervals were previously not
      available. Our point estimates were close to previous ones, and the standard
      deviations were generally quite small. Thus, even if debate over the meaning of
      the concept of lethal equivalents has not been entirely resolved, our results
      showed that the previous estimates are at least statistically meaningful.

PMID- 8760403
TI  - Electron spectroscopic imaging of antigens by reaction with boronated antibodies.
AB  - Two small homogeneous markers for electron spectroscopic imaging (ESI) containing
      eight dodecaborane cages linked to a poly-alpha, epsilon-L-lysine dendrimer were
      synthesized; one of these was made water soluble by the attachment of a
      polyether. The markers were coupled to the sulfhydryl group of (monovalent)
      antibody fragments (Fab') by a homobifunctional cross-linker. While the coupling
      ratios of the poorly water-soluble compound did not exceed 20%, the polyether
      containing variant reacted quantitatively. Its suitability for immunolabelling
      was tested in a study of the mechanism of the transcellular transport of an
      administered heterologous protein (bovine serum albumin, BSA) through ileal
      enterocytes of newborn piglets by endocytotic vesicles in comparison to
      conventional immunogold reagents. The post-embedding technique was employed. The
      boronated Fab' gave rise to considerably higher tagging frequencies than seen
      with immunogold, as could be expected from its form- and size-related physical
      advantages and the dense packing of BSA in the vesicles. The new probe, carrying
      the antigen-combining cleft at one end and the boron clusters at the opposite end
      of the oval-shaped conjugate, add to the potential of ESI-based
      immunocytochemistry.

PMID- 8760404
TI  - Quantitative electron spectroscopic imaging in bio-medicine: evaluation and
      application.
AB  - Electron spectroscopic imaging (ESI) with the energy-filtering transmission
      electron microscope enables the investigation of chemical elements in ultrathin
      biological sections. An analysis technique has been developed to calculate
      elemental maps and quantitative distributions from ESI sequences. Extensive
      experience has been obtained with a practical implementation of this technique. A
      procedure for more robust element detection has been investigated and optimized.
      With the use of Fe-loaded Chelex beads, the measurement system has been evaluated
      with respect to the linearity of the element concentration scale, the
      reproducibility of the measurements and the visual usage of image results. In
      liver specimens of a patient with an iron storage disease the detectability of
      iron was tested and we tried to characterize iron-containing components. The
      concentration measurement scale is approximately linear up to a relative section
      thickness of approximately equal to 0.5. Monitoring of this parameter is
      therefore considered to be important. The reproducibility was measured in an
      experiment with Fe-Chelex. The iron concentration differed by 6.4% between two
      serial measurements. Element distributions are in many applications interpreted
      visually. For this purpose the frequently used net-intensity distributions are
      regarded as unsuitable. For the quantification and visual interpretation of
      concentration differences mass thickness correction has to be performed. By
      contrast, for the detection of elements the signal-to-noise ratio is the
      appropriate criterion. Application of ESI analysis demonstrated the quantitative
      chemical capabilities of this technique in the investigation of iron storage
      diseases. Based on an assumed ferritin iron loading in vivo, different iron
      components can be discerned in liver parenchymal cells of an iron-overloaded
      patient.

PMID- 8760405
TI  - Imaging of thick sections of nervous tissue with energy-filtering transmission
      electron microscopy.
AB  - Electron microscopy of nervous tissue requires on the one hand nanometre
      resolution for the analysis of fine structures of nerve cell contacts, for
      instance synaptic vesicles, synaptic membranes and associated organelles. On the
      other hand, the visualization of the three-dimensional organization of nervous
      tissue on the level of dendrites and neurites is essential for the understanding
      of neuronal integration and also for a stereological evaluation of quantitative
      parameters such as size and shape of synaptic contact zones, number and
      distribution of synaptic vesicles, organization of cytoskeleton and distribution
      of organelles like mitochondria and endoplasmic reticulum. Therefore, it is
      necessary to have access to the fine structure and to the spatial organization
      within one sample. Energy-filtering transmission electron microscopy (EFTEM)
      enables the imaging of sections up to 1 micron thickness with a high resolution
      because the chromatic error due to inelastic scattering is avoided by selecting
      electrons within a restricted energy-loss range for imaging. The contrast depends
      strongly upon the section thickness, the selected energy range and the
      composition of the sample, so that optimum imaging conditions can be found for
      each object. Different staining protocols enable either a high global contrast or
      a selective staining of peculiar tissue properties. The three-dimensional
      organization can be visualized with stereopairs or with extended tilt series,
      which shows that characteristic structures as the synaptic junctions are
      detectable only within a narrow range of orientations to the electron beam. This
      is especially important for quantitative approaches with stereological tools
      which profit generally from the fact that a wide range of section thickness is
      available with EFTEM. EFTEM is therefore a powerful tool for the imaging of thick
      sections of biological materials with attractive possibilities of contrast tuning
      and advantages for stereological quantifications. The main benefit is the rapid
      and effective visualization of the three-dimensional organization of cells and
      tissues.

PMID- 8760406
TI  - Early mineralization of matrix vesicles in the epiphyseal growth plate.
AB  - Matrix vesicles (MVs) induce the primary mineralization in collagen-rich hard
      tissues such as bone, mineralizing cartilage and dentine. Calcium and phosphate
      ions accumulate at the inner MV membrane. This accumulation takes place in
      association with phospholipids alone and/or in association with Annexin V, which
      displays Ca ion channel activity when inserted in membranes; consequently,
      Annexin V may be involved in Ca uptake by matrix vesicles. The first crystal
      nuclei are formed at these macromolecules of the MV inner membrane. They grow to
      stable nanometre-sized particles, dots, which coalesce to form chains of dots
      along the macromolecules of the MV inner membrane. At the same time, or shortly
      afterwards, chains of these Ca phosphate dots also develop inside the MVs. The
      measured centre-to-centre distances between these dots represent approximately
      the distances between the nucleating sites, called active sites, along the MV
      matrix molecules. The mineralization does not stop at the MV membrane but expands
      continuously into the extravesicular region in radial directions to form nodules.
      These radiating Ca phosphate chains, which coalesce to form needles, are composed
      of such primary dots, which have developed at the nucleating sites of the
      corresponding macromolecules.

PMID- 8760407
TI  - Molecular biology of the feline immunodeficiency virus auxiliary genes.

PMID- 8760408
TI  - Feline immunodeficiency virus can infect a human cell line (MOLT-4) but
      establishes a state of latency in the cells.
AB  - Infectivity of feline immunodeficiency virus (FIV) in feline and human
      lymphoblastoid cell lines was examined using homogeneous populations of FIV
      derived from infectious molecular clones of strains TMZ and Petaluma, and two
      recombinant chimeric clones carrying gag, pol, vif and ORF-A from the
      heterologous virus. FIV from the clones with the env region of the Petaluma
      strain was shown to infect and establish provirus in a human lymphoid cell line
      (MOLT-4), although the FIV-infected cells did not produce any infectious viruses.
      By treatment of the infected MOLT-4 cells with a phorbol ester, infectious virus
      was rescued. To examine which stage of the life-cycle of FIV is blocked in these
      cells, we analysed transcription of FIV-14 in the cells by RT-PCR. FIV-specific
      RNA expression could not be detected. These results strongly suggest that latency
      of the virus in MOLT-4 cells is due to a failure in transcription.

PMID- 8760409
TI  - The structure and phylogeny of a new family of human endogenous retroviruses.
AB  - A novel endogenous retrovirus (ERV) designated XA34 was isolated from a human
      glioma cDNA library using low stringency hybridization with an ERV-9 env probe.
      Southern blot hybridizations with human genomic DNA revealed the presence of
      approximately 16 genomic copies closely related to XA34. Sequencing of a 2303 bp
      cDNA clone of XA34 showed that it belongs to a new ERV family. The XA34 ERV has
      recombined with an ERV-9-like retrovirus resulting in a truncated ERV-9-like env
      region that ends with an Alul-like 3' LTR. By using PCR, we isolated
      approximately 940 bp pol fragments from three additional members of this family,
      XA35, XA36 and XA37. A fifth member, XA38, was isolated and sequenced as a 4729
      bp genomic clone. The genomic XA38 clone spans from pol towards the 3' flanking
      region. The XA38 virus contains a more cryptic env region. The XA38 env is
      truncated in the transmembrane region and the virus then ends with three Alu
      repeats. Southern blot studies with human, chimpanzee, orangutan and squirrel
      monkey DNA show the presence of the XA34 family in all these species. That both
      the New and Old World monkeys have this ERV family means that the integration
      and/or amplification in the primate germ-line of XA34 probably took place about
      40-45 million years ago. The phylogeny and the closet relatives to ERV XA34 are
      discussed.

PMID- 8760410
TI  - The human immunodeficiency virus type 1 regulatory protein Tat inhibits
      interferon-induced iNos activity in a murine macrophage cell line.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection is frequently associated
      with concurrent infection by opportunistic pathogens, against which production of
      nitric oxide by host macrophages provides a first line of defence. We have
      investigated whether regulatory HIV-1 proteins, such as Tat, can modulate the
      activity of the inducible nitric oxide synthase (iNos) gene when expressed in
      stable transfectant lines of RAW264.7 cells. A bioassay for Tat, based on
      transactivation of an HIV-1 LTR-CAT reporter gene, allowed selection of Tat
      expressing cells. Parental and Tat-expressing macrophages accumulated identical
      levels of nitrite following lipopolysaccharide (LPS) stimulation. Interferon
      gamma (IFN-gamma) stimulation however, resulted in reduced levels of nitrite
      accumulation as a direct consequence of Tat expression. Conditioned media from
      Tat-expressing cells reduced the level of nitrite accumulation in parental cells
      following IFN-gamma stimulation but not stimulation with LPS. These results
      implicate HIV-1 Tat as a modulator of the IFN-gamma-specific signal transduction
      pathways leading to iNos expression.

PMID- 8760411
TI  - Genomic and biological alteration of a human immunodeficiency virus type 1 (HIV
      1)-simian immunodeficiency virus strain mac chimera, with HIV-1 Env, recovered
      from a long-term carrier monkey.
AB  - A macaque monkey infected with NM-3, a human immunodeficiency virus type 1 (HIV
      1)-simian immunodeficiency virus strain mac (SIVmac) chimeric virus with env,
      rev, tat and vpu derived from HIV-1 and LTR, gag, pol, vif and vpx derived from
      SIVmac, became a long-term carrier (more than 2.8 years). This monkey produced
      neutralizing antibodies to the original NM-3 as well as to the parental HIV-1.
      The virus recovered at 116 weeks replicated more rapidly and productively in
      macaque peripheral blood mononuclear cells than the original virus. The recovered
      virus was not neutralized either by antibodies raised early in the monkey or by a
      neutralizing monoclonal antibody that recognizes the V3 loop of HIV-1 Env,
      whereas both the early antibodies and the monoclonal antibody neutralized the
      original NM-3. Analysis of the virus genomic population revealed a few common
      mutations in the V3 region that caused amino acid changes. These data are
      consistent with the hypothesis that the virus escaped from the early antibodies
      and that the observed mutations contributed to this, as with HIV-1-infected
      humans. The observed mutations could equally well be the result of adaptation to
      simian cells. These results suggest that the HIV-1-SIVmac chimeric virus will be
      useful for investigating genetic variation of HIV-1 env and alteration of
      biological properties in vivo in relation to the host immune response.

PMID- 8760412
TI  - Fine-specificity of cytotoxic T lymphocytes which recognize conserved epitopes of
      the Gag protein of human immunodeficiency virus type 1.
AB  - Human immunodeficiency virus type 1 (HIV-1) Gag-specific cytotoxic T lymphocyte
      (CTL) responses were studied in seven seropositive long-term asymptomatic
      individuals (CDC A1) with stable CD4 counts for more than 8 years. Using a set of
      partially overlapping peptides covering the whole Gag, five 15-20-mer peptides
      were found to contain CTL epitopes. Further characterization of these epitopes
      revealed a new HLA-A25-restricted CTL epitope in p24, p24(203-212) ETINEEAAEW.
      This region of Gag is highly conserved in clades B and D of HIV-1. Naturally
      occurring amino acid sequences, containing p24(203)D (consensus HIV-1 clades A,
      C, F, G and H) or p24(204)I (HIV-2ROD) were not recognized by CTL recognizing the
      index peptide. No virus variants with mutations in this sequence were found in
      peripheral blood mononuclear cells from the HIV-1-infected individual concerned
      during the 8 year observation period, indicating that the virus had not escaped
      from the observed CTL response.

PMID- 8760413
TI  - Human antibodies that neutralize primary human immunodeficiency virus type 1 in
      vitro do not provide protection in an in vivo model.
AB  - Recently, conflicting data have been published about the ability of antibodies
      which efficiently neutralize T cell-adapted human immunodeficiency virus type 1
      (HIV-1) strains to neutralize primary HIV-1 strains in vitro and in vivo. Here we
      present data indicating that such antibodies fail to neutralize primary HIV-1
      strains in vivo. To this end, a newly developed chimeric human-to-mouse model was
      used, in which several aspects of primary HIV-1 infection are mimicked. Poly- and
      monoclonal antibodies protected the grafted human cells, in a dose-dependent way,
      from infection with T cell-adapted HIV-1 in this system. A human monoclonal
      antibody specific for the CD4 binding domain that efficiently neutralizes HIV-1
      IIIB in vitro did not protect the human graft from HIV-1 IIIB infection. None of
      the antibodies provided protection in the in vivo model against infection with
      primary HIV-1 strains, although they were able to neutralize these same strains
      in vitro.

PMID- 8760414
TI  - Cell death induced by cytopathic bovine viral diarrhoea virus is mediated by
      apoptosis.
AB  - Cells infected with two closely related isolates of bovine viral diarrhoea virus
      (BVDV), one cytopathic (CP) and one non-cytopathic (NCP), were examined for signs
      of apoptosis. The results from labelling DNA using terminal transferase and
      biotinylated dUTP and by observing oligonucleosomal-sized DNA fragmentation
      indicated that the CP strain of BVDV induced apoptosis in cell culture but the
      NCP strain did not. Induction of apoptosis correlated with infected cells
      undergoing apoptosis rather than interactions between infected and uninfected
      cells and the induction of apoptosis by CP BVDV was a dominant trait in cells co
      infected with both types of virus.

PMID- 8760415
TI  - Difference in virus-binding activity of two distinct receptor proteins for mouse
      hepatitis virus.
AB  - The receptor proteins, MHVR1 (Bgp C or splice variant of mmCGM1 containing two
      ectodomains) and MHVR2 (mmCGM2) have been reported to be functional receptors for
      MHV, although there was a significant difference in their virus-binding activity
      as determined by virus overlay protein blot assay (VOPBA). To compare the
      receptor function of these proteins, their virus-binding capacities were tested
      by using soluble forms of the proteins which lacked the transmembrane and
      intracytoplasmic domains. To estimate the amounts of these proteins expressed, an
      epitope of influenza HA protein, for which specific monoclonal antibody was
      available, was used as a tag. Recombinant soluble MHVR1 and MHVR2, expressed in
      RK 13 cells using recombinant vaccinia virus were secreted into the culture
      fluids of infected cells expressing these proteins. The inhibitory effect on
      virus infectivity of MHVR1 was shown to be about 500-fold higher than that of
      MHVR2. A similar disparity was observed in virus binding by VOPBA. These two
      proteins worked as functional receptors when they were expressed on resistant BHK
      21 cells. However, the efficiency of MHV infection in BHK-21 cells expressing
      MHVR1 was about 30-fold higher, as compared with those expressing MHVR2. These
      data show that the receptor function of MHVR1 was significantly higher than that
      of MHVR2 and suggests that the difference in susceptibility between SJL and
      BALB/c mice might be due to the specific receptor protein expressed in those
      animals.

PMID- 8760416
TI  - European brown hare syndrome virus: molecular cloning and sequencing of the
      genome.
AB  - The genome of the European brown hare syndrome virus (EBHSV), a calicivirus
      related to rabbit haemorrhagic disease virus (RHDV), was fully sequenced. It was
      7442 bases long and contained two ORFs. In RHDV, the 5' large ORF (ORF1) is
      predicted to encode a polyprotein precursor to the non-structural and capsid
      proteins. The small ORF (ORF2) encodes a predicted protein of 12 kDa. Alignment
      of sequences of EBHSV and RHDV showed 71% nucleotide identity; the changes were
      uniformly scattered over the whole genome. Minor differences could be detected
      when comparing two EBHSV sequences, indicating that EBHSV could vary to the same
      extent as RHDV. Four cleavage sites previously identified on the RHDV polyprotein
      were conserved in EBHSV. These sequencing data clearly show that EBHSV and RHDV
      share a similar genomic organization and confirm that EBHSV and RHDV are two
      distinct members within the family Caliciviridae.

PMID- 8760417
TI  - Genetic and phylogenetic clustering of enteroviruses.
AB  - Genetic and phylogenetic analysis of enteroviruses showed that in the 5'NCR
      enteroviruses formed three clusters: polioviruses (PVs), coxsackievirus A type 21
      (CAV21), CAV24 and enterovirus type 70 (ENV70) formed one cluster; coxsackievirus
      B isolates (CBVs), CAV9, CAV16, ENV71, echovirus type 11 (EV11), EV12 and all
      partially sequenced echoviruses and swine vesicular disease virus (SVDV) belonged
      to another cluster and bovine enteroviruses (BEVs) formed the third cluster. In
      the capsid coding region five clusters were seen: PVs, CAV21 and CAV24 formed one
      cluster (PV-like); ENV70 formed a cluster of its own; all CBVs, CAV9, EV11, EV12
      and SVDV formed the third cluster (CBV-like); CAV16, CAV2 and ENV71 belonged to
      the fourth cluster (CAV16-like) and BEVs formed their own cluster (BEV-like). In
      the 3'NCR the same clusters were seen as in the coding region suggesting a close
      association of the 3'NCR with viral proteins while the cellular environment may
      be more important in the evolution of the 5'NCR. Secondary structures were
      predicted in the 3'NCR, which showed two different patterns among the five
      clusters. A potential pseudoknot region common in all five clusters was
      identified. Although the BEV-like viruses formed a separate cluster in all
      genomic regions, in the coding region they seem to be phylogenetically related to
      the CAV16-like viruses.

PMID- 8760418
TI  - Equine rhinovirus serotypes 1 and 2: relationship to each other and to
      aphthoviruses and cardioviruses.
AB  - Equine rhinoviruses (ERVs) are picornaviruses which cause a mild respiratory
      infection in horses. The illness resembles the common cold brought about by
      rhinoviruses in humans; however, the presence of a viraemia during ERV-1
      infection, the occurrence of persistent infections and the physical properties
      are all more reminiscent of foot-and-mouth disease virus (FMDV). cDNA cloning and
      sequencing of the genomes of ERV-1 and ERV-2 between the poly(C) and poly(A)
      tracts showed that the serotypes are heterogeneous. Nevertheless, the genomic
      architecture of both serotypes is most similar to that of FMDV. Indeed, a
      comparison of the derived protein sequences of ERV-1 shows that their identity is
      greatest to FMDV. In contrast, most ERV-2 proteins are more related to
      encephalomyocarditis virus (EMCV) proteins than they are to FMDV or ERV-1. These
      results place ERV-1 alongside FMDV in the aphthovirus genus of the picornavirus
      family and indicate that this virus may serve as a model system for examining the
      biology of FMDV.

PMID- 8760419
TI  - Monoclonal antibodies raised against infectious haematopoietic necrosis virus
      (IHNV) G protein and a cellular 90 kDa protein neutralize IHNV infection in
      vitro.
AB  - Immune sera were obtained from four rainbow trout that had survived natural
      infection by infectious haematopoietic necrosis virus (IHNV), and five monoclonal
      antibodies (MAbs) were prepared against a Korean isolate of IHNV, IHNV-PRT. These
      immune sera and MAbs were characterized in terms of IHNV-neutralizing properties
      and reactivity in Western blots with the viral proteins of IHNV-PRT. All five
      MAbs and four immune sera neutralized IHNV-PRT to various extents. Antibodies in
      these immune sera recognized two structural proteins of IHNV, G and M1, and one
      protein with a molecular mass of 90 kDa. Of the five MAbs, three (AB9, AF6 and
      AG6) recognized the IHNV G protein, and the other two (AB7 and BC2) recognized
      the 90 kDa protein. The 90 kDa protein was found to be a cellular protein
      constitutively expressed at low levels in fish cells and expression of this
      protein was augmented by infection with IHNV and heat shock. MAbs specific to
      four stress proteins, hsp60, hsp70, hsp90 and grp94, failed to bind to this 90
      kDa protein. MAbs AB9 and AB7 reacted fairly broadly with six different IHNV
      strains. Together, these results indicate that (1) two IHNV proteins, G and M1,
      and a 90 kDa cellular protein are immunogenic, (2) G and the 90 kDa proteins
      contain neutralizing epitopes, and (3) the epitopes recognized by MAbs AB9 and
      AB7 are conserved among the six different IHNV strains.

PMID- 8760421
TI  - Mutational analysis of the influenza virus A/Victoria/3/75 PA protein: studies of
      interaction with PB1 protein and identification of a dominant negative mutant.
AB  - The RNA polymerase activity and PB1 binding of influenza virus PA mutants were
      studied using an in vivo-reconstituted polymerase assay and a two hybrid system.
      Deletions covering the whole PA protein abolished polymerase activity, but the
      deletion of the 154 N-terminal amino acids allowed PB1 binding, indicating that
      the PA protein N terminus is not absolutely required for this interaction.
      Further internal or C-terminal deletions abolished PB1 interaction, suggesting
      that most of the protein is involved in this association. As a novel finding we
      showed that a single amino acid insertion mutant, PAI672, was responsible for a
      temperature-sensitive phenotype. Mutant PAS509, which had a serine insertion at
      position 509, bound to PB1 like wild-type PA but did not show any polymerase
      activity. Over-expression of PAS509 interfered with the polymerase activity of
      wild-type PA, identifying PAS509 as a dominant negative mutant.

PMID- 8760420
TI  - Semi-permissive replication and functional aspects of the immune response in a
      cotton rat model of human parainfluenza virus type 3 infection.
AB  - A cotton rat (Sigmodon fulviventer) model of human parainfluenza virus type 3
      (HPIV-3) infection was used to study patterns of HPIV-3 replication in naive and
      immune hosts. Growth curves revealed that nasal and pulmonary tissues of naive
      animals were semi-permissive for virus replication, with amounts of progeny virus
      proportional to inoculating doses. In naive animals there was a total eclipse in
      nasal tissues beginning 4 h after inoculation. By contrast, there was only
      partial eclipse of virus in pulmonary tissues, most pronounced at 1 h after
      inoculation. Immune animals demonstrated a delayed eclipse in pulmonary tissues
      upon rechallenge. Infection with very low doses of HPIV-3 induced complete
      protection against high-dose challenge in the absence of systemic neutralizing
      antibody, suggesting a significant role for other systemic or local immune
      effectors.

PMID- 8760422
TI  - Large outbreak of swine influenza in southern Japan caused by reassortant (H1N2)
      influenza viruses: its epizootic background and characterization of the causative
      viruses.
AB  - In the winter of 1989 and the spring of 1990, there were large outbreaks of
      respiratory disease in two swine herds in Nagasaki Prefecture, southern Japan.
      Serological surveillance indicated that the majority of swine possessed
      antibodies to swine influenza virus H1 haemagglutinin and neuraminidase of early
      H3N2 influenza virus strains. Eight viruses were isolated from swine that showed
      typical clinical symptoms of influenza. The haemagglutinin and neuraminidase of
      these isolates were closely related to those of swine H1N1 and early human H3N2
      viruses, respectively. At least two types of haemagglutinin antigens,
      distinguished by two monoclonal antibodies, were involved in the outbreaks.
      Evolutionary analyses indicated that the haemagglutinin gene of the H1N2
      reassortants was closely related to those of a recent swine lineage (A/sw/HK/1/74
      and A/sw/Ehime/1/80 viruses). However, the neuraminidase genes of the H1N2
      reassortants were similar to those of swine N2 viruses which in turn are related
      to early human H3N2 viruses. A comparison of partial nucleotide sequences
      revealed that the six other genes of A/sw/Nagasaki/1/89 were derived from those
      of swine H1N1 virus.

PMID- 8760423
TI  - The S RNA genomic sequences of Inkoo, San Angelo, Serra do Navio, South River and
      Tahyna bunyaviruses.
AB  - The complete nucleotide sequences of the small (S) genomic RNA segments of five
      California (CAL) serogroup bunyaviruses (two Inkoo virus strains, San Angelo
      virus, Serra do Navio virus, South River virus and Tahyna virus) were determined.
      In agreement with previously published data concerning CAL serogroup viruses, the
      nucleocapsid (N) and non-structural (NSs) proteins were encoded in over-lapping
      open reading frames (ORFs). All N protein ORFs were 708 nucleotides in length and
      encoded a 235 amino-acid gene product. The NSs ORFs were either 279 or 294
      nucleotides in length, which would encode 92 or 97 amino-acid proteins,
      respectively. Comparative analysis of the nucleotide sequences and amino acids
      corresponding to the nucleocapsid protein resulted in a predicted relationship
      among these viruses that generally agreed with those determined by serology. The
      only exception was Inkoo virus, where comparisons based on the S RNA sequence and
      partial M RNA sequence suggest that this virus is more similar to Jamestown
      Canyon virus of the Melao complex than it is to viruses such as Tahyna and La
      Crosse viruses of the California encephalitis complex.

PMID- 8760424
TI  - Inkoo and Tahyna, the European California serogroup bunyaviruses: sequence and
      phylogeny of the S RNA segment.
AB  - Inkoo (INK) and Tahyna (TAH) viruses, European representatives of the California
      serogroup (CAL), genus Bunyavirus, family Bunyaviridae, are transmitted by
      mosquitoes and frequently infect man. The S segments of INK and TAH prototype
      strains were amplified, cloned and sequenced. INK S consists of 986 and TAH S of
      977 nucleotides (nt) coding for a nucleocapsid protein of 235 amino acids (aa)
      and, in an overlapping reading frame, for a nonstructural protein of 92 or 97 aa,
      respectively. By S segment sequences and phylogenetic analysis INK was seen to be
      most closely related to Jamestown Canyon virus, isolated in the USA (92.4% nt and
      96.6% aa identity), which is currently classified in a different subcomplex
      within the CAL viruses. TAH was genetically closest to Lumbo virus, isolated in
      Mozambique (89.0% nt and 94.1% aa identity). The data suggest that genetic
      variation within the CAL viruses is less related to geographical distance than to
      similarity in ecological cycles.

PMID- 8760425
TI  - Large RNA segment of Dugbe nairovirus encodes the putative RNA polymerase.
AB  - The nucleotide sequence of the large (L) RNA segment of Dugbe (DUG) virus
      (Nairovirus, Bunyaviridae) was determined, completing the first entire genome
      sequence of a nairovirus. The L segment comprised 12255 nucleotides, making a
      total genome size of 18855 nucleotides, and the ends showed identity with the
      ends of the medium (M) and small (S) genomic segments. A single open reading
      frame (ORF) was present in the viral complementary strand, sufficient to encode a
      protein of 459 kDa. The predicted protein sequence showed the core polymerase
      motifs characteristic of the RNA-dependent RNA polymerases of segmented negative
      stranded viruses. Comparison of the conserved motifs with the corresponding
      region of other segmented negative-strand viruses showed a closer relationship
      between nairoviruses and phleboviruses than with other Bunyaviridae or with other
      virus families. However, the core polymerase was the only function that could be
      assigned to a region of the DUG L gene.

PMID- 8760426
TI  - Sequence variability among different parvovirus B19 isolates.
AB  - Parvovirus B19 is the causative agent of a variety of clinical manifestations,
      ranging from asymptomatic to severe infection. The basis for this complex pattern
      of B19-associated diseases is as yet poorly understood. In general there are two
      different possibilities: firstly, the infected individuals may have a genetic or
      acquired predisposition, which renders them susceptible for a certain course of
      infection; secondly, differences in the B19 genome may result in different
      outcomes of infection. In order to investigate this second possibility we have
      partially sequenced the genomes of 20 different B19 isolates derived from serum
      samples from patients with various B19-associated diseases. Four distinct
      regions, which cover nearly half of the genome and include parts of the coding
      regions of all three major B19 proteins-NS1, VP1 and VP2, were selected for
      sequencing. Comparisons between the different extracted virus isolates at the DNA
      and protein levels revealed that isolates from patients with persistent
      parvovirus B19 infection show a tendency towards higher genome variability with
      respect to isolates derived from persons with acute infection.

PMID- 8760427
TI  - Species specificity for transduction of cultured cells by a recombinant LuIII
      rodent parvovirus genome encapsidated by canine parvovirus or feline
      panleukopenia virus.
AB  - We previously reported that a recombinant genome derived from the autonomous
      rodent parvovirus LuIII could be pseudotyped with capsids of the closely related
      viruses, H1 and minute virus of mice. To determine whether this was also possible
      with less related viruses, LuIII recombinant genomes containing a luciferase
      reporter were cotransfected into permissive cells together with plasmids
      expressing the capsid proteins of either feline panleukopenia virus (FPV) or its
      host range variant, canine parvovirus (CPV). We observed efficient packaging of
      the recombinant DNA into transducing virions that displayed the cell tropism of
      the virus that supplied the capsid. Thus, the FPV- and CPV-pseudotyped virions
      were able to transduce a feline cell line but they showed no transducing activity
      for the human NB324K line, which is permissive for LuIII. The transducing
      activity of the pseudotyped viruses was not inhibited by neuraminidase treatment
      of the permissive recipient cells, in contrast to that of virions packaged using
      LuIII capsid proteins. Furthermore, canine A72 cells (permissive for CPV but not
      FPV) were efficiently transduced by CPV-packaged but not by FPV-packaged LuIII
      recombinant genomes. Pseudotyped recombinants will be useful for elucidating
      parvovirus host range determinants since they enable the packaged DNA and each of
      the capsid proteins to be supplied independently. They should also facilitate
      control over the targeting of parvovirus vectors for gene transfer.

PMID- 8760428
TI  - Laboratory production of infectious stocks of rabbit oral papillomavirus.
AB  - Several small, raised lesions from the underside of the tongue of domestic
      rabbits were isolated, and an extract prepared and tested for the presence of
      rabbit oral papillomavirus (ROPV). Two weeks after inoculation of this extract
      into the underside of rabbit tongues, multiple small discrete, grey-white nodules
      were observed that reached a maximum size of 2 mm in diameter by 5 weeks. These
      lesions showed typical ROPV pathology, and nuclei stained positive for
      papillomavirus (PV) group-specific antigen (GSA) by immunocytochemistry. Tissue
      fragments from rabbit tongues were incubated with a suspension of ROPV and placed
      subrenally into athymic mice. After 60 days, cysts were removed, sections cut for
      histology, and a virus stock prepared. GSA staining and in situ hybridization
      demonstrated that the xenografts were morphologically transformed with areas
      showing strong nuclear staining for viral capsid antigen and ROPV DNA. Extracts
      prepared from the pooled xenografts contained infectious ROPV as demonstrated by
      inoculation into the undersurface of tongues of nonimmune New Zealand White
      rabbits. The results demonstrated that stocks of infectious ROPV can be prepared
      in the athymic mouse xenograft system for use in studies on the experimental
      transmission of a mucosal-targeting animal papillomavirus.

PMID- 8760429
TI  - Antibodies to human papillomavirus type 11 virus-like particles in sera of
      patients with genital warts and in control groups.
AB  - We analysed by ELISA a total of 478 human sera for the presence of antibodies to
      HPV-11 virus-like particles. The sera were obtained from patients with current
      genital warts (group CO), from males attending the hospital for fertility
      disorders (group MA), from blood donors (group BD) and from patients hospitalized
      for reasons unrelated to HPV infections (group HO). Antibody prevalence was
      higher in male patients of group CO (23.0%) as compared to males of groups MA
      (3.2%; P < 0.0001), HO (5.3%; P = 0.01) and BD (16.7%; NS). In addition, there
      was a significant difference in antibody titre between the males of group CO
      compared to group MA. Within the whole sample the absorbance of sera from females
      was higher than in specimens from males (P < 0.0001). A small subset of the sera
      was also tested by radioimmunoprecipitation assay (RIPA). There was good
      agreement between the data obtained by ELISA and RIPA.

PMID- 8760430
TI  - Characterization of the helicase and ATPase activity of human papillomavirus type
      6b E1 protein.
AB  - Human papillomavirus type 6b (HPV-6b) is one of the most common causes of human
      genital warts, an important sexually transmitted disease. Discovery of antiviral
      therapies for this condition has been hampered by the inability to propagate the
      virus using standard tissue culture techniques and through difficulties in
      expressing sufficient recombinant viral proteins in vitro. Replication of
      papillomavirus DNA requires two viral proteins, E1 and E2. In an effort to
      establish assays to discover compounds active against this virus, we have co
      expressed HPV-6b E1 and E2 proteins in insect cells. We demonstrate that the two
      proteins form a heteromeric complex which can be purified by sequence-specific
      DNA affinity chromatography. We also demonstrate that the complex has both E1
      associated ATPase and ATP-dependent DNA helicase activity and report further
      characterization of these functions.

PMID- 8760431
TI  - Common epitope on protein VI of enteric adenoviruses from subgenera A and F.
AB  - Western blot analysis with monoclonal antibodies, produced in response to
      immunization with gradient-purified adenovirus 41 (Ad41) virions, identified two
      epitopes of interest on protein VI of enteric adenoviruses. One epitope is unique
      to subgenus F adenoviruses (Ad40 and Ad41); the other epitope is common to
      subgenus A (Ad12, 18 and 31) and subgenus F(Ad40, 41) adenoviruses but is not
      shared by representative serotypes of subgenera B (Ad3 and 7), C(Ad1, 2 and 5),
      D(Ad8) or E (Ad4). Alignment of the deduced amino acid sequence of the genes
      encoding the protein VI precursor (pre-VI) of Ad40 and Ad41 (subgenus F), Ad12
      and Ad31 (subgenus A), Ad2 and Ad5 (subgenus C) shows that the N-terminal one
      third and C-terminal 23 amino acids of pre-VI are highly conserved. Within the
      central domain, pre-VI of subgenus F serotypes is more closely related to that of
      subgenus A serotypes than to pre-VI of the non-enteric subgenus C adenoviruses
      (Ad2 and Ad5). By expressing random oligonucleotide fragments of the Ad41 protein
      VI gene as part of a T7 gene 10 fusion protein, the two epitopes of interest were
      mapped to within the same 14 amino acid region in the central domain of protein
      VI. Given the association of subgenera A and F adenoviruses with paediatric
      gastroenteritis, the epitope shared by these serotypes may be functionally
      significant with respect to gut tropism. In addition, this epitope is potentially
      valuable as a target for the detection of enteric adenoviruses in clinical
      specimens.

PMID- 8760432
TI  - Activation of the protease from human adenovirus type 2 is accompanied by a
      conformational change that is dependent on cysteine-104.
AB  - Adenovirus codes for a protease the activity of which can be regulated in vitro
      by an 11 residue peptide (GVQSLKRRRCF) derived from another viral protein, pVI.
      Three cysteine residues, one in the activating peptide and two in the protease
      (C104 and C122), play a central role in both activation and catalysis. Expression
      of protease mutants in insect cells has shown that C104 is not essential for
      proteolytic activity. GVQSLKRRRCF also caused a concentration-dependent increase
      in tryptophan fluorescence of protease expressed in Escherichia coli that
      paralleled the increase in proteolytic activity, indicating that activation was
      accompanied by a conformational change. Tryptophan fluorescence of C104S was not
      increased by the addition of GVQSLKRRRCF, nor was the fluorescence of wild-type
      protease increased by the addition of the peptide analogues where cysteine is
      replaced by aspartic acid or serine, suggesting that C104 is involved in
      activation and C122 in catalysis.

PMID- 8760433
TI  - Mutations in the envelope gene of hepatitis B virus variants co-occurring with
      antibody to surface antigen in sera from patients with chronic hepatitis B.
AB  - Three clones of hepatitis B virus (HBV) DNA were propagated from sera of each of
      five patients with chronic hepatitis B who possessed hepatitis B surface antigen
      (HBsAg) and antibody to HBsAg in their serum. The clones were sequenced within
      the envelope gene (the preS1, preS2 regions and the S gene). Clones from four
      patients had various missense mutations involving codons 124-147 of the S-gene
      which encode amino acids in the loop structures that form the conformational,
      common antigenic determinant of HBsAg. Clones from three patients had Asn-130
      (Gly in the wild-type), which generated a potential N-glycosylation site, Asn-Thr
      Ser, spanning amino acids 130-132 of the S-gene product. In addition, clones from
      one patient had Arg-145 (Gly in the wild-type), which has been reported in escape
      mutants of HBV. One of the three clones from another patient had Ser-126 in place
      of lle or Thr in wild-type HBV, but the remaining two had no mutations known to
      affect expression of the common determinant of HBsAg. The remaining patient
      possessed HBsAg of subtype adr and anti-HBs specific for the w determinant.
      Clones from this patient did not reveal any mutations which are known to affect
      the common antigenic determinant of HBsAg.

PMID- 8760434
TI  - Severe outcome of hepatitis B virus (HBV) infection and lack of HBV e antigen
      defective virus emergence in patients homozygous for HLA class I alleles.
AB  - In the Mediterranean region almost all patients with hepatitis B virus (HBV)
      related cirrhosis are anti-HBV e antigen (anti-HBeAg)-positive and carriers of
      HBeAg-negative virus mutants. The six members of a family who acquired HBV
      infection were recently studied: two siblings developed cirrhosis with
      persistence of HBeAg positivity, whereas their parents and two more siblings
      cleared the virus. The two cirrhotic patients showed homozygosity for HLA class I
      by phenotype, which is a rare occurrence in the general population, while the
      other family members were heterozygous for HLA class I. The sequencing analyses
      of the entire viral DNAs isolated from both cirrhotic patients showed that the
      two viral genomes were almost identical and no mutation preventing HbeAg
      synthesis or viral gene expression was present. These findings might suggest that
      homozygosity for HLA class I molecules might be responsible for an insufficient
      response to the virus, favouring chronic outcome of the infection and the long
      lasting persistence of HBV populations that produce HBeAg.

PMID- 8760435
TI  - Protease-activated lymphoid cell and hepatocyte recognition site in the preS1
      domain of the large woodchuck hepatitis virus envelope protein.
AB  - A site capable of strictly host- and cell type-specific recognition was
      identified in the preS1 domain of woodchuck hepatitis virus (WHV) through the use
      of antipeptide antisera generated against the extreme N-terminal fragment of the
      large virus envelope protein. The crucial determinant of this binding site was
      mapped to amino acids 10-13. Although a synthetic analogue of the site was highly
      immunogenic, natural WHV envelope did not display the site activity unless it was
      modified by proteolysis or acidic pH treatment, indicating an internal location
      of the determinant in viral envelope. Synthetic peptides encompassing the
      sequence of this site bound woodchuck lymphoid cells and hepatocytes in a species
      restricted manner which followed characteristics of a specific ligand-receptor
      interaction, although their ability to interact with lymphoid cells was
      considerably greater than that for hepatocytes. In WHV-infected animals, a
      natural antibody to the identified cryptic cell-binding site arose independently
      of that directed against epitopes of unmodified virus envelope and its appearance
      constituted the earliest immunovirological indicator of virus invasion. Our
      results demonstrated that the preS1 domain of the large WHV envelope protein is
      endowed with the species- and cell type-specific recognition site which is
      protected against antibody surveillance by the natural tertiary structure of the
      protein and we suggest that proteolytic cleavage is required to induce the
      binding activity.

PMID- 8760436
TI  - Immediate early protein IE63 of herpes simplex virus type 1 binds RNA directly.
AB  - The herpes simplex virus type 1 (HSV-1) immediate early protein IE63 acts post
      transcriptionally to affect RNA 3'-processing and splicing. Functional domains
      such as the RGG box and zinc-finger motifs potentially provide the protein with
      RNA binding capacity. Here, IE63 protein expressed in E. coli, purified by
      affinity chromatography and used in RNA binding assays, demonstrated similar
      binding to RNA substrates containing poly(A) sites from different temporal
      classes of HSV-1 genes, RNA containing splice site recognition sequences and RNA
      containing no recognized processing motifs. Competition binding assays showed
      that IE63 binding could be competed out, suggesting that IE63 binds RNA weakly.
      HSV-1 infection results in an increase or stabilization in vitro of protein
      binding to poly(A) site-containing RNAs; IE63 is required for this effect. RNA
      binding assays combining purified IE63 with protein from mock-infected and HSV-1
      infected nuclear extracts demonstrated no effect on protein-RNA binding patterns.

PMID- 8760437
TI  - Role of cis-acting sequences of the ICPO promoter of herpes simplex virus type 1
      in viral pathogenesis, latency and reactivation.
AB  - A mutant herpes simplex virus type 1, termed delta Tfi, with a 350 bp deletion of
      the Sp1, NF-kappaB, TAATGARATs, C/EBP and F2 DNA-binding elements from -420 to 
      70 relative to the transcriptional start site of ICPO (Vmw 110), was generated
      and characterized. The efficiency of plating of delta Tfi was reduced on Vero
      cells and it expressed correctly initiated ICPO RNA in the presence of
      cycloheximide, although RNA levels were 2.5-fold lower than with wild-type (KOS)
      and marker-rescued (delta TfiR) viruses. This was consistent with a demonstrated
      reduction in ICPO protein expression for delta Tfi at early times post-infection
      and a 3-fold reduction in ICPO-dependent transactivation of the ICP6 promoter.
      KOS, delta Tfi and delta TfiR replication in murine corneas and trigeminal
      ganglia were comparable when measured on a complementing cell line, but delta Tfi
      titres appeared 15- to 50-fold lower when measured on Vero cells. delta Tfi was
      correspondingly less virulent than wild-type or marker-rescued viruses in both
      immunocompetent and SCID mice. delta Tfi, however, established and reactivated
      from latency with efficiencies comparable to wild-type and marker-rescued
      viruses. These results demonstrate that although this deletion of the ICPO
      promoter results in lower levels of ICPO in vitro and decreased virulence in
      vivo, the establishment of and reactivation from latency are unaffected. This
      indicates that elements which regulate ICPO expression and virulence during acute
      infection may be distinct from those involved in reactivation.

PMID- 8760438
TI  - Characterization of the genes, including that encoding the viral proteinase,
      contained in BamHI restriction fragment 9 of the pseudorabies virus genome.
AB  - We describe the nucleotide sequence, transcription pattern and open reading
      frames (ORFs) located on BamHI restriction fragment 9 (0.406-0.435 map units) in
      the unique long segment of the pseudorabies virus (PRV) genome. The fragment
      contains three nested genes with a common 3' end. The 5' ends of the
      corresponding 0.9, 1.7 and 3.3 kb mRNAs have been mapped. Fragment BamHI-9
      contains three complete ORFs, ORF1, ORF2 and ORF2.5. ORF1, which is within the
      3.3 kb transcript, encodes a protein with an apparent molecular mass of 60 kDa
      which is homologous to the product of the herpes simplex virus type 1 UL25 gene.
      The 1.7 kb mRNA contains ORF2, whose product is homologous to the herpesvirus
      proteinases, while the 0.9 kb transcript contains ORF2.5, which probably encodes
      the assembly protein precursor. ORF2 was identified as the PRV proteinase gene
      following expression in E. coli, using the product of ORF2.5 as the substrate
      protein.

PMID- 8760439
TI  - Identification of a 56 kDa putative bovine herpesvirus 1 cellular receptor by
      anti-idiotype antibodies.
AB  - Polyclonal anti-idiotype antibodies (anti-ids) to anti-bovine herpesvirus 1 (BHV
      1) MAbs blocked virus infection in cell cultures, indicating that they contain
      internal images of a viral attachment protein(s). In the present study anti-id
      (anti-83) of BHV-1 gB was used as a probe to detect the cellular receptor. Anti
      id specifically identified a 56 kDa protein in radioimmunoprecipitation analysis
      (RIPA) of Madin-Darby bovine kidney (MDBK) cell membranes suggesting the
      involvement of this cell surface component in BHV-1 binding. Anti-83 pretreated
      with MAb 83 failed to identify the 56 kDa cellular component proving its
      specificity for the reacting epitope of MAb 83. The recognition of 56 kDa protein
      by anti-id was inhibited by prior incubation of radiolabelled membrane proteins
      with BHV-1 suggesting that the ligands competed for the same binding sites on the
      cells. 35S-Radiolabelled BHV-1 virions also bound a 56 kDa protein from purified
      MDBK cell membrane proteins in a virus overlay protein blot assay. RIPA using
      anti-id as probe detected the 56 kDa protein in permissive MDBK cells but not in
      non-permissive bat lung cells. The protein nature of the 56 kDa component was
      confirmed by protease treatment of membranes which resulted in abolition of the
      56 kDa signal in RIPA. In addition, purified 56 kDa protein inhibited
      biotinylated BHV-1 attachment in flow cytometry. These findings indicate that the
      56 kDa protein identified by anti-id is a putative receptor for BHV-1.

PMID- 8760441
TI  - Functional analysis of C-terminal deletion mutants of Epstein-Barr virus
      thymidine kinase.
AB  - Thymidine kinase (TK) activity was detected following expression of the TK gene
      of Epstein-Barr virus (EBV) using the pET expression plasmid and E. coli BL21
      (DE3)pLysS. To study the amino acid residues required at the C terminus of the
      EBV TK protein for enzymatic activity, a series of C-terminal deletion mutants
      was generated by direct truncation, linker insertion or PCR mutagenesis to create
      stop codons at particular sites. Deletion of nine residues from the C terminus
      caused a 35% reduction in TK activity, while a ten-residue deletion completely
      abolished the activity. A single point mutation at residue Cys570, corresponding
      to Cys336 of herpes simplex virus TK, did not alter the TK activity. Single amino
      acid changes within the last seven to ten residues also did not affect activity.
      The results indicate that maintenance of the conformation of the C terminus is
      important for enzyme activity.

PMID- 8760440
TI  - Induction of apoptosis in epithelial cells by Epstein-Barr virus latent membrane
      protein 1.
AB  - Epstein-Barr virus (EBV) induces human B cell transformation and is closely
      associated with nasopharyngeal carcinoma. The expression of an EBV latent
      membrane protein, LMP-1, protects B cells from apoptosis by up-regulating the
      expression of a cellular oncogene, bcl-2. LMP-1 also transforms rodent
      fibroblasts and affects the differentiation, morphology and growth of human and
      rodent epithelial cells. In this report, we describe a novel finding that high
      level expression of the LMP-1 gene in a human epithelial cell line (RHEK-1)
      induces apoptosis, characterized by chromosomal DNA fragmentation in the
      transfected cells. In particular, such an effect was more apparent under serum
      starvation. We also found that in the transfected RHEK-1 cells, LMP-1 expression
      neither affected bcl-2 expression nor led the cells to grow in semisolid soft
      agar medium. These results indicate that LMP-1 may participate in the development
      of EBV-associated epithelial malignancy via a mechanism different from that seen
      in B cell or fibroblast transformation.

PMID- 8760442
TI  - Cloning, restriction endonuclease mapping and partial sequence analysis of the
      genome of human herpesvirus 7 strain JI.
AB  - Human herpesvirus 7 (HHV-7) is a recently isolated herpesvirus that has been
      shown to be related to human cytomegalovirus and human herpesvirus 6 and to be a
      member of the betaherpesvirus subgroup. Here we report the cloning, restriction
      endonuclease mapping and partial sequence analysis of HHV-7 strain JI DNA. Virus
      particles were obtained from the supernatant of infected SupT1 cells, the DNA
      isolated by proteinase K treatment-phenol extraction, and full-length viral DNA
      was purified and isolated on a pulsed-field gel. Aliquots of this highly purified
      material were treated in the following ways: (i) sonicated and end-repaired to
      create short randomly sheared fragments for cloning into M13mp 18-Smal vector
      DNA; (ii) cut with EcoRI for cloning into EcoRI-cut lambda ZAPII or lambda DASHII
      vectors; (iii) cut with BamHI for cloning into BamHI-cut lambda ZAP-Express or
      lambda DASHII vectors. Partial nucleotide sequencing of the M13 clones followed
      by detection of open reading frames and their translation allowed the
      identification of homologues through FASTA searches of the database. Relevant M13
      clones were used as probes to isolate corresponding lambda phage clones, which
      could tentatively be mapped to the genome on the basis of presumed genetic
      collinearity between HHV-7 and HHV-6. Genomic "walking' between EcoRI and BamHI
      lambda genomic libraries enabled overlapping neighbouring clones to be identified
      and mapped. Each of these clones was analysed to map BamHI, EcoRI, Sa/l, Smal and
      Xhol restriction endonuclease sites to provide complete endonuclease maps for the
      entire genome.

PMID- 8760443
TI  - Characterization of the Lymantria dispar nucleopolyhedrovirus 25K FP gene.
AB  - The Lymantria dispar nucleopolyhedrovirus (LdMNPV) gene encoding the 25K FP
      protein has been cloned and sequenced. The 25K FP gene codes for a 217 amino acid
      protein with a predicted molecular mass of 24870 Da. Expression of the 25K FP
      protein in a rabbit reticulocyte system generated a 27 kDa protein, in close
      agreement with the molecular mass predicted from the nucleotide sequence. The
      gene is located between 40.3 and 40.8 map units on the viral genome. It is
      transcribed in a counterclockwise direction with respect to the circular map at
      late times during the infection cycle from a consensus baculovirus late promoter.
      The LdMNPV and Autographa californica nucleopolyhedrovirus (AcMNPV) 25K FP
      proteins exhibit 52% amino acid identity with several regions showing greater
      than 75% identity. Homologues to the AcMNPV orf59 and orf60 were also identified
      upstream (with respect to the genome) of the 25K FP gene in LdMNPV and exhibit
      52% and 45% amino acid identity, respectively.

PMID- 8760444
TI  - Sequential appearance and accumulation of pathognomonic markers in the central
      nervous system of hamsters orally infected with scrapie.
AB  - Both infectivity and TSE-specific amyloid protein (also referred to as protease
      resistant- or prion protein, PrP) are pathognomonic markers for transmissible
      spongiform encephalopathies (TSE). This paper presents a new densitometric method
      for the quantification of TSE-specific amyloid protein and its application to
      studying the pathogenesis of scrapie in Syrian hamsters after infection with
      scrapie strain 263K. A first study established a close correlation between
      infectivity and TSE-specific amyloid protein with a doubling time of 2-2.6 days
      in the brain and cervical spinal cord for both markers. The ratio of infectivity
      and TSE-specific amyloid protein was relatively constant at a mean value of about
      10(6) protein molecules per infectious unit during the course of infection. A
      subsequent study addressed the temporal-spatial spread of infection in the
      central nervous system by tracing the accumulation of the pathological protein.
      The pathogenetic process was first detected in the spinal cord between vertebrae
      T4 and T9, and then showed an anterograde and retrograde spread with a rate of
      0.8-1.0 mm/day. There were also some indications for a possible alternative route
      of spread of infection from the periphery to the brain, other than via the spinal
      cord. Involvement of the spleen did not appear essential for the early
      pathogenesis in hamsters orally infected with the 263K strain of scrapie.

PMID- 8760445
TI  - Replication of scrapie in spleens of SCID mice follows reconstitution with wild
      type mouse bone marrow.
AB  - SCID mice are resistant to intraperitoneal infection with 10(3) and 10(4)
      intracerebral ID50 units of ME7 scrapie agent whereas they develop disease after
      intracerebral challenge. However, higher doses introduced, by intraperitoneal or
      subcutaneous routes, produce disease. Immunocompetent mice of the same strain
      (CB20) developed scrapie following either intracerebral or intraperitoneal
      infection. Bioassay of spleens from SCID mice infected with 10(-1) dilutions of
      ME7 scrapie by intraperitoneal, intracerebral or abdominal subcutaneous injection
      showed traces or low levels of infectivity in spleen. However, subcutaneous
      injection beneath the skin of the neck failed to infect the spleen. CB20 bone
      marrow reconstitution of SCID mice resulted in the regeneration of a normal
      lymphoid architecture in the spleen. Spleens from these reconstituted mice,
      infected intracerebrally with a 10(-1) dilution of ME7 contained high levels of
      infectivity. These results suggest that the ability to replicate scrapie agent in
      spleen or lymphoid tissue depends on the restoration of normal lymphoid structure
      and in particular the presence of differentiated follicular dendritic cells. The
      possibility that SCID mice can select minor strains of scrapie which are normally
      unrecognized in cloned ME7 is discussed.

PMID- 8760446
TI  - Protease-resistant PrP deposition in brain and non-central nervous system tissues
      of a murine model of bovine spongiform encephalopathy.
AB  - Infectivity within the central nervous system has been demonstrated by the
      transmission of bovine spongiform encephalopathy (BSE) from affected cattle to
      inbred laboratory mice. Sedimentable, protease-resistant PrP (PrPSc) has also
      been extracted from BSE-affected cattle brain. Both infectivity and PrPSc have
      been reported in the lymphoreticular tissues of sheep and mice clinically and
      preclinically affected with scrapie. Neither infectivity nor PrPSc has yet been
      detected in non-neural tissues of naturally occurring, clinical cases of BSE in
      cattle. We have used a murine model of BSE (301V isolate in VM/Dk mice) to
      investigate when and where PrPSc accumulates. PrPSc was detected both in brain
      and in extraneural sites prior to the onset of clinical symptoms. This murine BSE
      model differs, however, in four important aspects from our previously published
      findings for murine scrapie models: (a) PrPSc was found relatively late into the
      incubation period; (b) after intracerebral inoculation, PrPSc was found in brain
      before it was found in other tissues; (c) no PrPSc was found in most of the
      spleens from clinically affected animals after intracerebral inoculation; and (d)
      even after intraperitoneal infection, PrPSc was detected in brain first.

PMID- 8760447
TI  - Tomato golden mosaic virus open reading frame AL4 is genetically distinct from
      its C4 analogue in monopartite geminiviruses.
AB  - Tomato golden mosaic virus (TGMV) is a bipartite geminivirus with six well
      characterized genes. An additional open reading frame (ORF), AL4, lies within the
      essential AL1 gene. Recent studies of monopartite, dicot-infecting geminiviruses
      have revealed that mutations in their analogous C4 ORFs have host-specific
      effects on infectivity, symptomatology, virus movement and/or viral DNA
      accumulation. We have investigated whether TGMV has a similar host-specific
      requirement for AL4. The phenotypes of three TGMV al4 mutants were determined in
      a range of hosts, which included species that revealed c4 mutant phenotypes for
      monopartite geminiviruses. Each TGMV al4 mutant was indistinguishable from wild
      type TGMV in all hosts tested. Additional analyses of double mutants revealed no
      evidence for functional redundancy between AL4 and the AL3, or AR1 genes. In
      contrast to the putative C4 proteins of monpartite geminiviruses, TGMV AL4, if it
      is expressed, is either non-functional, or functionally redundant with an
      essential TGMV gene product.

PMID- 8760448
TI  - Frequent occurrence of recombinant potyvirus isolates.
AB  - We have performed a systematic search for recombination in the region encoding
      coat protein and the 3' non-translated region in natural isolates of potyviruses,
      the largest group of plant RNA viruses. The presence of recombination, and the
      localization of the cross-over points, were confirmed statistically, by three
      different methods. Recombination was detected or suspected in 18 out of 109
      potyvirus isolates tested, belonging to four out of eight virus species, and was
      most prevalent in potato virus Y, clear in bean common mosaic virus, and possible
      in bean yellow mosaic and zucchini yellow mosaic viruses. Recombination was not
      detected in the four other potyvirus species tested, including plum pox virus,
      despite the availability of numerous sequences for this last species. Though it
      was not specifically researched, no evidence for inter-specific recombination was
      found. For several reasons, including the fact that only a minor portion of the
      genome was analysed, the above figures certainly represent an underestimate of
      the extent of recombination among isolates of potyviruses, which might thus be a
      common phenomenon.

PMID- 8760449
TI  - The 5'-terminal region of a tombusvirus genome determines the origin of
      multivesicular bodies.
AB  - Multivesicular bodies (MVB) are membranous cytoplasmic inclusions that are
      invariably associated with tombusvirus infections regardless of the virus
      species, the host, or the tissue examined. MVB are virus-induced structures since
      they are absent from tissues of healthy plants and are always present both in
      infected plants and protoplasts. MVB derive from peroxisomes in cells infected by
      a number of tombusviruses including cymbidium ringspot virus (CymRSV) and from
      mitochondria in cells infected by another tombusvirus, carnation Italian ringspot
      virus (CIRV). By using common restriction sites in full-length infectious clones,
      hybrid clones of these two viruses were constructed. In addition, a mutant of
      CIRV was prepared in which the protein encoded by the first open reading frame
      was shortened by 22 amino acids. All mutant transcripts were viable and infected
      Nicotiana benthamiana plants. Infected leaf tissue samples were collected,
      processed for thin sectioning, and observed in the electron microscope. The
      origin of MVB was shown to be under the control of the 5' region of the viral
      genome. A sequence as short as about 600 nucleotides in ORF 1 contained the
      determinants for formation of MVB from peroxisomes or mitochondria.

PMID- 8760450
TI  - Immunological characterization of rice tungro spherical virus coat proteins and
      differentiation of isolates from the Philippines and India.
AB  - Rice tungro spherical virus (RTSV) has an RNA genome of more than 12 kb with
      various features which classify it as a plant picornavirus. The capsid comprises
      three coat protein (CP) species, CP1, CP2 and CP3, with predicted molecular
      masses of 22.5, 22.0 and 33 kDa, respectively, which are cleaved from a
      polyprotein. In order to obtain information on the properties of these proteins,
      each was expressed in E. coli, purified as a fusion to the maltose-binding
      protein and used for raising a polyclonal antiserum. CP1, CP2 and CP3 with the
      expected molecular masses were detected specifically in virus preparations. CP3
      is probably the major antigenic determinant on the surface of RTSV particles, as
      was shown by ELISA, Western blotting and immunogold electron microscopy using
      antisera obtained against whole virus particles and to each CP separately. In
      some cases, especially in crude extracts, CP3 antiserum detected several other
      proteins (40-42 kDa), which could be products of CP3 post-translational
      modification. No serological differences were detected between the three CPs from
      isolates from the Philippines, Thailand, Malaysia and India. The CP3-related 40
      42 kDa proteins of the Indian RTSV isolate have a slightly higher electrophoretic
      mobility (42-44 kDa) and a different response to cellulolytic enzyme
      preparations, which allows them to be differentiated from south-east Asian
      isolates.

PMID- 8760451
TI  - Secretory expression of a single-chain insulin precursor in yeast and its
      conversion into human insulin.
AB  - A synthetic single-chain porcine insulin precursor (PIP) gene and an alpha-mating
      factor leader sequence (alpha MFL) gene obtained by the PCR method are inserted
      between the promoter and 3'-terminating sequence of the alcohol dehydrogenase
      gene ADH1 in plasmid pVT102-U to form plasmid pVT102-U/alpha MFL-PIP. The single
      chain insulin precursor is expressed and secreted to the culture medium by
      Saccharomyces cerevisiae transformed by pVT102-U/alpha MFL-PIP. The precursor is
      purified and converted into human insulin by tryptic transpeptidation. The
      purified human insulin is fully active and can be crystallized. The overall yield
      of human insulin is 25 mg per liter of culture medium.

PMID- 8760453
TI  - Effect of nucleotides 37 and 38 on cleavage of tRNAPhe precursors.
AB  - Splicing is required for tRNA maturation when the precursors contain the introns.
      In order to determine whether nucleotides 37 and 38 affect splicing, yeast
      tRNAPhe precursors with different nucleotides 37 and 38 were prepared by in vitro
      mutagenesis and cleaved by the purified yeast tRNA-splicing endonuclease. The
      precursors with purine nucleotides at N37 and N38 were found to be the best
      substrates for the enzyme. When N37 and N38 were replaced by pyrimidine
      nucleotides, few precursors could be cleaved by the endonuclease. If one is
      pyrimidine nucleotide, the other one is purine nucleotide at these positions, the
      cleavage efficiencies are between the two groups of precursors stated above. The
      pyrimidine nucleotides at these positions might affect the fine structures of the
      precursors or the distance between the splicing sites, so that the precursors can
      not be fixed or anchored on the enzyme well, leading to the poor cutting.

PMID- 8760454
TI  - Comparison of dark- and light-adapted carp retinas with NADPH diaphorase
      staining.
AB  - The carp retina was examined by NADPH diaphorase histochemistry to determine if
      the staining pattern of retinal cells was changed depending on the adaptation
      state of the retina. When dark-adapted for 5 h, ellipsoids of inner segments of
      both rods and cones and some horizontal cells were heavily stained. Staining was
      also found in subpopulations of amacrine cells and ganglion cells. In addition,
      Muller cells were strongly positive for NADPH diaphorase. When light-adapted for
      5 h, ellipsoids of photoreceptors and ganglion cells were less intensely stained,
      whereas Muller cells and horizontal cells became negative for NADPH diaphorase.
      Furthermore, rod ON-center bipolar cells were clearly stained. The difference of
      staining of amacrine cells between dark- and light-adapted retinas was not
      significant. The differences in diaphorase-staining pattern between dark- and
      light-adapted retinas suggest that Muller cells, some horizontal cells and rod ON
      center bipolar cells contain inducible nitric oxide synthase, whose induction
      depends on the adaptation state.

PMID- 8760455
TI  - Cobalt ions enhance light responsiveness of carp cone horizontal cells in low
      calcium.
AB  - Effects of cobalt ions (Co2+) on horizontal cells in low extracellular calcium
      were examined in isolated, superfused carp retinas. While 0.1 mmol/L Co2+
      completely suppressed both rod- and cone-driven horizontal cells in normal
      Ringer's solution, it enhanced light responses of cone horizontal cells in low
      (0.1 mmol/L) calcium. The enhancement of the cone horizontal cell response by
      Co2+ was not caused by changes in light responsiveness of cone photoreceptors.
      Moreover, application of 50 mumol/L IBMX, an inhibitor of phosphodiester enzyme,
      reduced the suppressive effect of 0.1 mmol/L Co2+ in normal Ringer's solution. In
      consequence, the above-described enhancement of the cone horizontal cell light
      responsiveness may be due to a depolarization of cones caused by low calcium,
      which increases the activity of voltage-dependent calcium channels at cone
      terminals.

PMID- 8760456
TI  - Interaction between fulvic acids of different origins and active oxygen radicals.
AB  - Using the spin trapping technique, the interaction between fulvic acids (FAs) of
      different origins and the active oxygen radicals was studied. The active oxygen
      radicals under study included superoxide anion (O2.-) produced by xanthine
      oxidase (XOD) and stimulated polymorphonuclear leukocytes (PMN) of human being
      and hydroxyl radical (.OH) produced from Fenton's reaction. It has been found
      that the FAs from both Kaschin-Beck disease (KBD) region and non-KBD region can
      accelerate the production of .OH and scavenge O2.-. FA from peat can scavenge
      both O2.- and .OH. The results show that the behavior of KBD and non-KBD FAs
      differs clearly from peat FA. It has been concluded that the superoxidation
      damage of KBD induced by FA is mainly due to hydroxyl radical reaction initiated
      in biological system.

PMID- 8760457
TI  - Mitotic dynamics.
AB  - A new model for mitotic dynamics of eukaryotic cells is proposed. In the
      kinetochore motor-midzone motor model two kinds of motors, the kinetochore motors
      and the midzone motors, play important roles in chromosome movement. Using this
      model the chromosome congression during prometaphase, the chromosome oscillation
      during metaphase and the chromatic segregation during anaphase are described in a
      unified way.

PMID- 8760458
TI  - Overexpression of a reversion-related protein in the revertant RR cells.
AB  - The cDNA insert of the plasmid p14-6 is found to be the 3'-untranslated region
      (3'-UTR) of the transcription factor for human interleukin-6, NF-IL6. This 3'-UTR
      is actively transcribed in the revertant cell line RR, which contains the p14-6
      plasmid integrated into its genomic DNA. Simultaneously a protein specifically
      bound to this 3'-UTR is expressed in significantly larger amounts. Its
      overexpression is apparently related to the reversion of the malignant cellular
      phenotype. The properties of this protein, named BNF, and possible reasons for
      its overexpression are discussed, and hypothesis on the mechanism of reversion of
      the RR cells is proposed.

PMID- 8760459
TI  - Active expression of G gamma globin gene on chromosome 11 with Yunnanese A gamma
      delta beta)0-thalassemia deletion in MEL cells.
AB  - A permanent lymphocyte cell line of a heterozygote with Yunnanese (A gamma delta
      beta)0-thalassemia deletion, associated with an increased production of G gamma
      globin in adult, was founded using Epstein-Barr virus transformation. The hybrids
      of the lymphocyte cell and mouse erythroleukemia cell (MEL) were achieved and the
      hybrids containing human chromosome 11 were selected with the monoclonal antibody
      53/6. The subclones containing only either the normal or the abnormal human
      chromosome 11 were separated and the expression of the human globin genes was
      studied. Expression of the beta-globin gene, but not the G gamma and A gamma, was
      observed in the hybrids containing only the normal human chromosome 11, while
      active expression of the G gamma globin gene was observed in the hybrids
      containing only the abnormal human chromosome 11. These results have confirmed
      that the DNA deletion in the beta-globin gene cluster is the cause of persistent
      active expression of the G gamma globin gene in the Yunnanese mutant.

PMID- 8760460
TI  - Orientational and directional selectivities of visual neurons in the superior
      colliculus of the cat.
AB  - Based on quantitative analyses of the response characteristics of visual neurons
      in the superior colliculus to moving optical bar stimuli, it is demonstrated for
      the first time that the visual neurons in superior colliculus of the cat have, to
      some extent, orientational selectivity. The significance of this selectivity is
      discussed in reference to its morphological substrate and physiological
      functions. In addition, both the directional and orientational selectivities in
      the superior colliculus are relatively weak when compared with those in the
      primary visual cortex, and the majority of the neurons prefer upward or downward
      motion in the visual field.

PMID- 8760461
TI  - Characteristics of the inward-rectifying potassium current in mouse ventricular
      myocytes and its relation to early after-depolarization.
AB  - The properties of the inward-rectifying potassium current (IK1) were studied in
      the single myocytes isolated from adult mouse ventricles by the whole-cell patch
      clamp technique for the first time. Most of the properties of IK1 including
      channel conductances, activation, inactivation, rectification and external K+
      sensitivity in mouse ventricular myocyte were similar to those in other species,
      but the current-voltage (I-V) curve of mouse ventricular myocyte showed no
      negative slope, i.e the slope in the range of membrane potential 50 mV positive
      to the reversal potential (VRev) was virtually flat and remained at a low current
      level ((59 +/- 39) pA). Under the superfusion of Tyrode's solution with 3 mmol/L
      K+ and 3 mmol/L Cs+, IK1 in the above region nearly decreased to zero, and then
      the early after-depolarization (EAD) occurred. The results suggest that this
      distinctive characteristic of IK1 in mouse ventricular myocyte may relate to the
      high susceptibility to EAD in mouse myocardium. The inhibition of IK1 seems to be
      a prerequisite for the occurrence of EAD in this experiment.

PMID- 8760462
TI  - Molecular replacement study on form-B monoclinic crystal of insulin.
AB  - The form-B monoclinic insulin crystal was obtained from the sodium citrate buffer
      with 1% zinc chloride, keeping phenolic content between 0.76% and 1.25%. Its
      space group is P2(1), cell constants are: a = 4.924 nm, b = 6.094 nm, c = 4.818
      nm, beta = 95.8 degrees. There are 6 insulin molecules which form a hexamer. The
      initial phase was obtained by using rotation function program of X-PLOR program
      package and molecular packing program of our laboratory. The molecular model was
      chosen from 4 zinc bovine insulin hexamer. After the preliminary refinement by
      using the macromolecular rigid body refinement technique, the molecular model was
      further refined and adjusted by using the energy-minimizing stereochemically
      restrained least-squared refinement on the difference Fourier maps. The final R
      factor is 22.4% at 0.3 nm resolution, the r.m.s. deviations from standard bond
      length and bond angle are 0.0022 nm and 4.7 degrees, respectively.

PMID- 8760463
TI  - Reaction of hydroxyl radical with phenylpropanoid glycosides from Pedicularis
      species: a pulse radiolysis study.
AB  - Using pulse radiolysis technique, the reaction between hydroxyl radical and 7
      phenylpropanoid glycosides: echinacoside, verbascoside, leucosceptoside A,
      martynoside, pediculariosides A, M and N which were isolated from Pedicularis
      were examined. The rate constants of these reactions were determined by transient
      absorption spectra. All 7 phenylpropanoid glycosides react with hydroxyl radical
      at high rate constants within (0.97-1.91) x 10(10)L.mol-1.s-1, suggesting that
      they are effective hydroxyl radical scavengers. The results demonstrate that the
      numbers of phenolic hydroxyl groups of phenylpropanoid glycosides are directly
      related to their scavenging activities. The scavenging activities are likely
      related to o-dihydroxy group of phenylpropanoid glycosides as well.

PMID- 8760464
TI  - Interaction of electron leak and proton leak in respiratory chain of mitochondria
      -proton leak induced by superoxide from an electron leak pathway of univalent
      reduction of oxygen.
AB  - By incubating the isolated rat myocardial mitochondria with xanthine-xanthine
      oxidase, an exogenous superoxide (O2.-) generating system, and by ischemia
      reperfusion procedure of isolated rat heart as an endogenous O2.- generating
      system, it was found that both sources O2.- showed the same injurious effects on
      mitochondrial function resulting in (i) increasing proton leak rate, lowering
      proton pumping activity and H+/2e ratio of respiratory chain, and (ii) decreasing
      transmembrane potential of energized mitochondrial inner membrane by succinate
      oxidation. The injurious effects of O2.- on these mitochondrial bioenergitical
      parameters mentioned above exhibited a dosage- or reaction time-dependent mode.
      O2.- has no effects on the electron transfer activity and transmembrane potential
      of nonenergized mitochondria. Being a superoxide scavenger, 3,4-dihydroxylphenyl
      lactate showed obvious protection effects against damage of both exogenous
      superoxide sources from xanthine-xanthine oxidase system and endogenous O2.-
      source from ischemia-reperfused heart on proton pumping activity, H+/2e ratio and
      transmembrane potential of energized mitochondria. The experimental results
      presented here clearly showed that O2.- radicals induce an increase of proton
      leak in mitochondria directly related to the molecular mechanism of early phase
      damage of ischemia-reperfused heart, and also provide evidence to support our
      recent proposed hypothesis that electron leakage to oxygen to form O2.- in
      respiratory chain is one of the mechanical cause of proton leakage in
      mitochondria.

PMID- 8760465
TI  - Processing of global and local properties--an analysis with event-related brain
      potentials.
AB  - The different processing of global and local properties of compound visual
      stimuli was studied with event-related brain potentials (ERPs) in the present
      experiment. It was found that, compared with the identification of global
      properties, the discrimination of local properties elicited longer RTs, lower
      accuracies, increased amplitudes of PI, decreased amplitudes of N1, and longer
      latencies of N2 and P3. The conflict of global and local properties increased the
      amplitudes of P2, decreased the amplitudes of P3, and prolonged latencies of N2
      and P3. These results indicated that the advantage of global processing occurs at
      an early perceptual stage, and the attentional mechanisms for global and local
      processing may be different.

PMID- 8760466
TI  - Construction of an insecticidal baculovirus expressing insect-specific neurotoxin
      AaIT.
AB  - Considering the factors which affect gene transcription, translation and the
      stability of mRNA, without changing the amino acid composition of the encoded
      polypeptide, AaIT gene encoding insect-specific neurotoxin was designed and
      synthesized according to bias in codon choice, overall G+C content and G+C
      content of bases at the third position in codons of polyhedrin genes of
      baculovirus and of plant genes as well. AaIT gene was fused behind a synthetic
      gp67 signal sequence and then recombined into the genome of Trichoplusia ni
      nuclear polyhedrosis virus (TnNPV) by transfer vector pSXIV VI+X3. The
      recombinant virus TnNPV-AaIT (occ+-gal-) was screened. The results of Southern
      blotting and SDS-PAGE demonstrated that AaIT gene had integrated into the genome
      of virus and expressed. Bioassays on the 3rd-instar Trichoplusia ni larvae showed
      that recombinant viruses TnNPV-AaIT could shorten the time of killing insect and
      improve the efficacy of killing agronomically important insects.

PMID- 8760468
TI  - Natural killer cell cytotoxicity assay with time-resolved fluorimetry.
AB  - A new time-resolved fluorimetric method for the measurement of natural killer
      (NK) cell cytotoxicity has been developed by labelling the target cell K562 with
      a new synthesized fluorescence marker KLUK. The method has advantages of higher
      sensitivity, time-saving, good reproducibility and has no radioactivity problems.
      A satisfactory result is obtained by comparing it with 51Cr release method. It
      demonstrates that the new marker provides an alternative to currently used
      radioactive markers for the assessment of in vitro cellular cytotoxicity.

PMID- 8760467
TI  - Investigation on inhibition of biological effects of endothelin.
AB  - The effects of a series of substances on the biological function of endothelin
      (ET) are reported. The substances used are: synthetic inhibitors of endothelium
      derived relaxing factors (EDRFs), inhibitor of big-endothelin converting enzyme
      phosphoramidon, antiserum of endothelin, antagonists of endothelin A receptor
      BQ123 and JKC301, and two Chinese anti-snake venom herb medicines Lobelia
      radicans Thumb and Taris polyphylla Smith var. chinensis (Franch) Hara. The
      results showed that inhibiting the production of nitric oxide (NO) could
      stimulate ET release from vascular endothelium, elevate plasma ET and increase
      blood pressure. These changes could be reversed by L-arginine (L-Arg), the
      substrate of nitric oxide synthase (NOS). The amount of ET released by arterial
      endothelium could be increased or inhibited by inhibiting or stimulating the
      synthesis of prostacyclin (PGI2). The plasma ET level and blood pressure in both
      SHR and WKY rats could be decreased by giving phosphoramidon (PhR). The above
      results indicate that the biological effects of ET could be antagonized by
      inhibiting the synthesis or release of ET, decreasing the level of plasma ET,
      blocking the binding of ET with its receptor and using some Chinese anti-snake
      venom herb medicines.

PMID- 8760469
TI  - Atomic force microscopic study on topological structures of pBR322 DNA.
AB  - Plasmid pBR322 DNA (0.5 mg/mL) isolated from Escherichia coli HB101 was suspended
      in Tris-HCI-EDTA (1 mol/L-0.1 mol/L, pH 8.5); then a drop of the above solution
      was deposited on freshly cleaved mica substrate. After adsorption for about 1 mm,
      the sample was stained with phosphotungstic acid. The residual solution was
      removed with a piece of filter paper. Afterwards the sample was imaged with a
      home-made atomic force microscope (AFM) in air. The AFM images of pBR322 DNA with
      a molecular resolution have been obtained. These images show that pBR322 DNA
      exists in several different topological structures: (i) relaxed circular DNA with
      a different diameter; (ii) supercondensed DNA with different particle sizes;
      (iii) dimeric catenane connected by one relaxed circular molecule and another
      close-compacted molecule which might be either supercoiled or intramolecular
      knotted form; (iv) oligomeric catenane with multiple irregular molecules in which
      DNA is interlocked into a complex oligomer; (v) possibly-existing intermediates
      formed from monomer to oligomer.

PMID- 8760470
TI  - Preliminary study on the molecular structure of 3' region of Duchenne muscular
      dystrophy (DMD) gene in Chinese.
AB  - Number and order of HindIII exon-containing fragments (Hd) at 3' region of DMD
      gene were studied systematically using 16 partly-overlapping cDNA subprobes which
      were produced from dystrophin cDNA 9-14 with each of 9 restriction endonucleases.
      There are 25 Hd fragments corresponding to cDNA 9-14 in DMD gene. Since then, the
      exact length and the new order of Hd fragments are established. A new 2.1 kb
      fragment (Hd 55) is revealed; a 5.2 kb fragment (formerly designated as Hd 59) is
      excluded and the existence of a controversial 3.2 kb fragment (Hd 64) is
      confirmed. Besides, three new exons were revealed by comparing the PvuII and the
      XbaI hybridization patterns with the HindIII hybridization patterns for these
      cDNA subprobes. It is concluded that there are at least 66 Hd fragments, or 79
      exons in DMD gene basing on the discovery of three additional exons. The
      corresponding relationship between the 66 Hd fragments and the SfiI large scale
      physical map has been studied, and at least 17 Hd fragments or 19 exons were
      shown to be distributed in the last fragment (IJ fragment) of the SfiI map of DMD
      gene.

PMID- 8760471
TI  - Regulation of tissue-type plasminogen activator and plasminogen activator
      inhibitor type-1 in cultured rat Sertoli and Leydig cells.
AB  - New data are provided to show that (i) rat Sertoli cells produce two types of
      plasminogen activators, tissue type (tPA) and urokinase type (uPA), and a
      plasminogen activator inhibitor type-1 (PAI-1); (ii) both tPA (but not uPA) and
      PAI-1 secretion in the culture are modified by FSH, forskolin, dbcAMP, GnRH, PMA
      and growth factors (EGF and FGF), but not by hCG and androstenedione (delta 4);
      (iii) in vitro secretion of tPA and PA-PAI-1 complexes of Sertoli cells are
      greatly enhanced by presence of Leydig cells which produce negligible tPA but
      measurable PAI-1 activity; (iv) combination culture of Sertoli and Leydig cells
      remarkably increases FSH-induced PAI-1 activity and decreases hCG- and forskolin
      induced inhibitor activity as compared with that of two cell types cultured
      alone. These data suggest that rat Sertoli cells, similar to ovarian granulosa
      cells, are capable of secreting both tPA and uPA, as well as PAI-1. The
      interaction of Sertoli cells and Leydig cells is essential for the cells to
      response to hormone stimulation for tPA and PAI-1 secretion.

PMID- 8760472
TI  - In situ amplification of DNA fragments specific for human Y chromosome in
      cellular nuclei by PCR.
AB  - Using single primer pairs Y3 and Y4 in situ polymerase chain reaction (in situ
      PCR) was successfully performed on the specimen slides of peripheral leukocytes.
      By both of the direct digoxiginin-11-dUTP incorporation into PCR products with in
      situ PCR (direct in situ PCR) and in situ PCR followed by detection of in situ
      hybridization (indirect in situ PCR), DNA fragments specific for human Y
      chromosome were obviously amplified in cellular nuclei of specimens on the
      slides. The results were verified by Southern analysis. The methodology of in
      situ PCR and its application were discussed.

PMID- 8760473
TI  - Dynamic changes of mechanically activated channels and K+ channels at injury site
      of peripheral nerve in rat.
AB  - Ectopic ion channels developed locally at the injury site after nerve damage by
      light ligation around common sciatic nerve of the rats. Different channel types
      have different processes of formation, accumulation and degeneration. During the
      first three days after injury, mechanically activated channels that are modulated
      by CA++ channel activities first appeared. As the nerve fibers begin to be
      excited by TEA, a blocker of K+ channels, suggesting that the accumulation of K+
      channels, the responsibility of mechanically activated channels was declining.
      Onset of K+ channels was from the 3rd postoperative day and lasted up to the
      fiftieth day. This time course of K+ channel development was closely related to
      allodynia and hyperalgesia of neuropathic animal behaviour. The results suggest
      that chronic contraction injury induces a dynamic change in the ectopic
      mechanically activated channels and K+ channels at the injury site of nerve and
      there is an interchange in the development time courses of the mechanically
      activated channels and K+ channels.

PMID- 8760474
TI  - Inhibitory effects of isoproterenol on PAF-induced endothelial cell permeability
      and morphological changes.
AB  - Using a model to study vascular permeability under hydrostatically perfused
      bovine pulmonary artery endothelial cell (EC) monolayers and a software to
      automatically analyse cell morphological parameters in a computer image
      workstation, the effects of isoproterenol (IPN) on platelet-activating factor
      (PAF)-induced changes in EC monolayer permeability and cell morphological
      parameters were studied. Albumin has the fortifying effect on endothelial barrier
      function. After treatment of EC monolayer with 10(-8) mol/L PAF, trans-monolayer
      permeability increased, cell surface area decreased, and intercellular space
      enlarged. As pretreatment with 10(-4) mol/L IPN, PAF-induced EC permeability
      increment and morphological changes were blocked. The results suggest that EC
      contraction and intercellular gap expansion are important mechanisms for PAF
      induced high vascular permeability. IPN inhibits the effects of PAF via
      stabilization of EC morphology and prevention of intercellular gap formation.

PMID- 8760475
TI  - 13C-methacetin breath test parameter S for liver diseases diagnosis.
AB  - The mechanism of 13C-methacetin breath test is set forth clearly with the
      analysis of pharmacokinetics mode, and the measuring method of 13C-methacetin
      breath test and its clinical applications in the diagnosis of liver diseases are
      reported in detail. On the basis of comprehensive analysis of the clinical test
      data, the advanced diagnostic parameter S is of important significance for the
      application and development of breath test.

PMID- 8760476
TI  - Neurobiological mechanisms of the meridian and the propagation of needle feeling
      along the meridian pathway.
AB  - The present experiments attempt to find the meridian phenomenon and how the
      needle feeling propagates along the given meridian channels. The neurobiological
      mechanisms of the meridian were studied with neuroelectrical recording from the
      motor neurons and CB-HRP retrograde histochemistry technique in both rats and
      cats. The results demonstrated that most, but not all, of alpha motor neurons
      supplying a muscle group of a given meridian were selectively activated by
      afferent inputs originating not only from homonymous or heterogeneous, but
      synergistic muscle, but also from the skin nerve overlying the muscle group of
      the homonymous meridian. However, the afferent inputs from the heterogeneous
      meridian have very weak or no effect. On the other hand, the labeled motor
      neurons supplying a given meridian muscles from a discrete longitudinal column
      with a definite bound in the lateral ventral horn. There are oriented dendro
      dendristes projections between the labeled motor neurons. The characteristics of
      both selective responses of the motor neurons to afferent inputs and their neuro
      anatomical arrangements in spinal cord offer neurobiological evidence for the
      meridian phenomenon.

PMID- 8760477
TI  - The need for medical ecology.

PMID- 8760478
TI  - Violence and alienation: an issue of public mental health.
AB  - This century has seen more extensive social and political change than ever
      before. Some, such as antibiotics, has been beneficial, but much has led to
      alienation and political and cultish ideologies. These in turn have spawned
      widespread violence. Not all violence is physical; some is inner-directed and can
      lead to suicide. Some is inspired by genuine idealism but too often this
      degenerates into cruelty excused as a struggle with alleged evil. Violence can be
      nation- or even continent-wide-Africa, Latin America, Middle East, Indochina, but
      also Europe including the former Soviet Union. It is also local, especially in
      inner cities throughout the world, linked to drugs but also as mindless
      vandalism. Solutions must be both at the macro level, through the UN and its
      agencies; the UN charter must be revised to allow appropriate intervention within
      national borders. At the local level, underlying causes such as human rights
      abuses and unemployment can be put right. Much more research is needed but action
      cannot await the findings. The author's recent personal experience in Osijek in
      former Yugoslavia shows that the most important factor is the people themselves,
      but outsiders can provide knowledge, resources and support.

PMID- 8760479
TI  - Medicine, population and war.
AB  - Do medicine and health-care increase population size as well as individual
      quality of life? Do large and rapid increases in numbers tend to put greater
      pressure on and therefore increase competition for scarce resources and in turn
      raise the level and intensity of human conflict and violence? Does this
      hypothesized succession of events present health professionals with weighty
      ethical and practical dilemmas requiring urgent attention? It is argued here that
      it does.

PMID- 8760480
TI  - On the barbaric nature of boxing: thoughts following the panorama debate on
      banning boxing after yet another death.

PMID- 8760481
TI  - Embryological considerations on a multiple vascular anomaly in a child.
AB  - Coiling and kinking of the internal carotid artery are considered of remarkable
      importance in the pathogenesis of cerebral ischaemic episodes, especially in
      adults. The authors describe the case of a seven months old infant who underwent
      aortic and bilateral cerebral angiography because of severe neurological
      symptomatology. Besides serious malformations of the aorta and major vessels,
      both coiling of the left internal carotid artery and kinking of the right
      internal carotid artery were found. The arterious anomalies of the aortic
      branches are probably due to the deranged development of the two subclavian
      arteries and, in particular, of the right one. Owing to the patient's age, the
      carotid alterations are also consequent to an abnormal development of the
      arterious district deriving from the primitive aortic archs, especially the third
      arch.

PMID- 8760482
TI  - Motor nerve sprouting induction by a nerve explant in normal and vitamin E
      deficient rats.
AB  - Sprouting induction by a peripheral degenerating nerve has been evaluated in
      normal and vitamin E-deficient rats. A piece of sural nerve was grafted close to
      the peroneal nerve of the same animal: at one and two months after grafting thin
      unmyelinated axons were visible in the graft and they were sometimes functionally
      active; when nerve explant was frozen before grafting, sprouting induction did
      not take place either in controls or in vitamin E-deficient animals. No
      difference was noted in sprouting induction between the two groups, while
      degeneration showed a different time course. Some hypotheses of possible stimuli
      of sprouting induction are discussed.

PMID- 8760484
TI  - Quantitative determination of thymic eosinophilia in swine.
AB  - Thymuses from 512 slaughtered pigs weighing about 160 Kilos, were subjected to
      histological examination. All thymuses displayed a focal or diffuse eosinophilia
      in the connective tissue septa and in the lymphoid tissue, especially in the
      medulla. Quantitative determination of cellular density and eosinophils was
      performed on 30 cases, by image analysis, and the number of eosinophils was
      compared to the number of Hassall's bodies. Statistical analysis demonstrated a
      significant difference in the number of eosinophils between cases with focal
      eosinophilia and those with diffuse pattern (P < 0.001). The higher quantity of
      eosinophils was present, the higher number of Hassall's bodies was calculated per
      unit area of medulla (P < 0.001). The significance of this eosinophilia is
      obscure. It may be related to the elimination of cellular catabolism products and
      this agrees with the possible phagocytic activity of Hassall's bodies. However,
      further investigation concerning the physiopathology of the thymus must take into
      consideration the presence of the eosinophils granulocytes in this organ.

PMID- 8760483
TI  - Comparative study of sensitive and vegetative innervation of external and
      internal anal sphincter muscles in different mammals.
AB  - Proprioceptive innervation of the external anal sphincter muscle and the
      organization of the vegetative and sensitive nerve components of the internal and
      sphincter muscle have been studied in different mammals. The findings of typical
      muscle spindles in the external anal sphincter muscle were constant in the pig,
      frequent in the goat and cow, rare in the sheep and horse and absent in the roe
      and rabbit. In the pig, muscle spindles were observed in the entire extension of
      the muscle, while in the sheep, goat, cow and horse, the receptors were found
      only in the cranial portion of the muscle. In all the species studied, the
      internal anal sphincter muscle had numerous ganglion cells, isolated or grouped,
      and rare Pacinian, Pacinian-like, and Golgi-Mazzoni corpuscles. Their functional
      role has been hypothesized.

PMID- 8760485
TI  - Light and electron microscopic demonstration of methylene blue accumulation sites
      in the murine cornu Ammonis after supravital staining.
AB  - The distribution pattern of methylene blue in the murine hippocampus after
      supravital dye application was studied light and electron microscopically. The
      characteristic, selective staining of nerve cell subpopulations occurred only in
      the presence of oxygen. Solitary or grouped polymorph neurons, i.e. non-pyramidal
      nerve cells, mainly located in the stratum pyramidale and stratum oriens of the
      cornu Ammonis were intensely stained. Ultrastructurally, the dye could easily be
      identified as an electron dense precipitate. MB had accumulated within the
      cytoplasm with no apparent association with cell organelles and was additionally
      also found within the nucleus. Precipitate was also detected within profiles of
      nerve cell processes. MB seemed to accumulate at the plasma membrane in the early
      phase of staining. The ultrastructure of the stained cells was significantly
      damaged by the intracellularly bound dye. This oxygen-dependent selective
      staining is probably followed by the generation of reactive oxygen species and
      subsequent oxidative stress for the neurons; this phenomenon suggests a strong
      affinity of a subpopulation of non-pyramidal cells in the cornu Ammonis to oxygen
      and therefore a high vulnerability to hypoxia.

PMID- 8760486
TI  - Immunohistochemical research on the atrial natriuretic factor (ANF) in rat
      atrioventricular valves.
AB  - Immunohistochemical research on atrioventricular valves in normotensive rats
      revealed that valvular myocardiocytes are the seat of synthesis of the atrial
      natriuretic factor (ANF). The endocardial cells that border the atrial and
      ventricular surfaces also had granules which were positive for ANF. The ANF which
      is also synthesized in the valvular myocardiocytes moved towards the cardiac
      cavity and crossed the endocardial cells in the more distal areas of the valvular
      edge. At the same time, the ANF was routed into the blood vessels in the areas
      close to implantation.

PMID- 8760487
TI  - Intermediate filaments of human Sertoli cells in germinal alterations.
AB  - Immunohistochemical techniques were used to examine testis biopsy specimens in
      subjects of different ages, in whom histological examination of the seminiferous
      tubules revealed a reduction in number, immaturity or absence of germinal
      elements. Our aim was to detect changes in the expression of the vimentin and
      cytokeratin (8-18-19) intermediate filaments in Sertoli cells. The use of anti
      vimentin antibodies demonstrated intense Sertoli cell positivity in all the cases
      studied, confirming that germinal alterations do not interfere with the
      expression of these filaments. The Sertoli cells of the subjects affected by
      pathological conditions also reacted positively to anti-cytokeratin antibodies.
      This finding was constant in all the testes, showing evident signs of germinal
      immaturity. In contrast, anti-cytokeratin positivity was not observed in the
      control specimens after the pre-pubertal stage. Our findings show that persisting
      co-expression of vimentin and cytokeratin filaments in the Sertoli cells of
      productive subjects may be a marker of germinal cell degeneration.

PMID- 8760488
TI  - Histochemical characterization of the mucins of the epithelial cells in the chick
      embryo proventriculus.
AB  - The histochemical characteristics of the epithelial mucins, which are produced by
      the lining epithelium, the superficial glands and the compound glands of the
      proventriculus were investigated in the chick embryo from the 7th day of
      incubation to hatching. Results showed that the time of appearance of the
      carboxylated, sulphated and neutral mucosubstances differed at the three
      investigated sites. From the 13th to the 19th day of incubation, intense
      production of the various mucins was detected at the three sites. However, the
      modality of intracytoplasmatic storage and the production of mucins in both the
      cells of the lining epithelium and the superficial glands appeared to differ from
      those observed in the cells of the compound glands. At the 20th and 21st day, the
      mucins were primarily produced by the lining epithelium and the superficial
      glands, whereas production diminished in the compound glands. Furthermore, from
      the 7th to the 17th day of incubation, the cells of the principal ducts of the
      compound glands showed the same histochemical characteristics and modality of
      production as those of the glandular cells of the compound glands. On the other
      hand, from the 18th day to hatching, these cells assumed the same characteristics
      as those of the lining epithelium and of the superficial glands.

PMID- 8760489
TI  - Cooperation and conflict in the evolution of individuality. II. Conflict
      mediation.
AB  - Evolutionary transitions in the units of selection require the promotion of
      cooperation and the regulation of conflict among the lower level units. For
      multicellular organisms to emerge as a new unit of selection, the selfish
      tendencies of their component cells had to be controlled. Theoretical results
      indicate organisms may regulate this internal conflict and competition in several
      ways: by reducing the somatic mutation rate, by sequestering cells in a germ line
      and by directly reducing the benefits to cell of defecting.

PMID- 8760490
TI  - Positive association between copia transposition rate and copy number in
      Drosophila melanogaster.
AB  - Rates of copia transposition were determined directly, by cytological in situ
      hybridization analysis of sites of copia insertion in progeny of males from
      sublines of an inbred strain with different genomic copia copy numbers. Copia
      transposition rate was positively and nonlinearly associated with copia copy
      number. This relation cannot be simply explained by mutations in a single host
      factor that normally suppresses transposition, or by mutations in copia elements
      themselves. We postulate that the number of copia virus-like particles, necessary
      for copia transposition, could depend nonlinearly on copia copy number.
      Deleterious side-effects of the transposition process may be an important force
      controlling copia copy number in natural populations.

PMID- 8760491
TI  - Antisense to NPY-Y1 demonstrates that Y1 receptors in the hypothalamus underlie
      NPY hypothermia and feeding in rats.
AB  - Neuropeptide Y (NPY) is a highly potent endogenous peptide which when injected
      into the medial hypothalamus causes spontaneous eating behaviour and an intense
      fall in body temperature (Tb). This study used antisense oligodeoxynucleotides
      (ODNs) to determine whether the Y1 subtype of NPY receptor could underlie these
      remarkable physiological responses. In the unrestrained rat, the ventromedial
      hypothalamus (VMH) which is highly reactive to NPY was injected with antisense
      for NPY (aNPY), Y1 receptors (aNPY-Y1) and mismatched controls (mNPY; mNPY-Y1).
      After cannulae were implanted bilaterally in the brain of 19 rats, 0.4 or 0.8
      microgram per 0.8 microliter of the phosphorothioate synthesised ODNs were
      delivered to the VMH of the rats at 12 h intervals over 2 d. Only the lower dose
      of aNPY-Y1, but not aNPY, evoked an intense phasic rise in the Tb following each
      micro-injection. Simultaneously, 0.4 microgram per 0.8 microliter of aNPY-Y1, but
      not aNPY, suppressed feeding behaviour after a sequence of micro-injections and
      on the following day. Body weights and locomotor activity of the rats likewise
      declined concomitantly with the hyperthermia and hypophagia caused by the Y1
      receptor antisense. Neither of the control ODNs for NPY or Y1 receptors injected
      similarly in the VMH of the rats exerted any effects on these measures. These
      results clearly provide convincing evidence that in the VMH the Y1 subtype of NPY
      receptor mediates, in part, the neuronal mechanisms responsible for spontaneous
      feeding and hypothermia produced by native NPY when applied directly to this
      structure. The concurrent decline in body weight and activity caused by aNPY-Y1
      could be caused by the episodes of hyperthermia.

PMID- 8760492
TI  - Anti-CD4 therapy for AIDS suggested by mathematical models.
AB  - HIV-1 infection typically involves a long clinical latency stage during which CD4
      counts decline slowly. For the later part of the clinical latency stage it was
      found recently that this is a highly dynamic phase characterized by rapid
      turnover rates. Clinical latency can therefore be considered as a quasi
      equilibrium state in which CD4 and HIV-1 turnover are in almost perfect balance.
      Here we consider this quasi-equilibrium to be the stable steady state of a simple
      host-parasite model in which the parasite (HIV-1) level is determined by the
      availability of infectable hosts (activated CD4+ T cells). Such models adequately
      account for the clinical data on the evolution of drug resistant mutants
      appearing after the administration of anti-HIV drugs. The model suggests a novel
      therapeutic approach for AIDS: reducing the CD4 count slightly will strongly
      reduce the HIV load. Combining this anti-CD4 treatment with conventional anti-HIV
      therapy would prevent the outgrowth of drug resistant mutants.

PMID- 8760493
TI  - Selective phonotaxis by males in the Majorcan midwife toad.
AB  - Males are expected to exhibit mating preferences when there is high variance in
      the quality of females or when males are limited to a small number of matings. In
      the Majorcan midwife toad, Alytes muletensis, the male performs parental care by
      carrying the eggs wrapped in a string around his hind legs. Both sexes possess
      courtship vocalizations which they use to advertise receptivity. We looked for
      evidence of male mating preferences in a phonotaxis arena in which males were
      presented with two alternative synthetic female calls. We predicted that males
      should prefer to mate with large females because of maternal effects on egg size,
      and that this preference would be manifest by selective phonotaxis toward low
      frequency calls. We also predicted that males should prefer high intensity calls
      as indicators of the energetic or motivational state of the female. Contrary to
      our prediction, males did not exhibit a preference for low frequency calls. The
      results suggest that there is stabilizing selection on call frequency and
      directional selection on call intensity.

PMID- 8760494
TI  - Plasticity of the somatosensory cortical map in macaque monkeys after chronic
      partial amputation of a digit.
AB  - Activity-dependent changes in cortical representational maps have been reported
      in many studies of adult mammals. Limits in extent of change have been attributed
      to limited divergence in the thalamocortical projection. However, studies have
      commonly been restricted to animals surviving less than a year following
      relatively modest peripheral sensory perturbations. After extensive
      deafferentation and long-term survival, more extensive changes, seemingly beyond
      the limits of thalamocortical divergence, have been reported. We report changes
      in the somatotopic map in area 3b of an adult macaque monkey, in which part of
      the index finger of one hand had been amputated two years previously. The
      representation of the remaining stump occupied the whole region of area 3b
      normally devoted to the representation of the entire digit. The skin surrounding
      the stump appeared to have been hyperinnervated by axons severed during the
      amputation. The hyperinnervation of remaining skin may have reactivated neurons
      of the somatosensory system silenced by the amputation, leading to the recovery
      of a cortical map but with a modified organization.

PMID- 8760495
TI  - Predicting the size and direction of sex differences in measures of emotion and
      personality.
AB  - Plutchik's (1980, 1994) psychoevolutionary theory, which posited eight basic
      emotions, was used as a framework for the organization of Lazarus and Folkman's
      (1984) coping strategies and Bem's (1981) gender-schematic items regarding
      equivalent motivations and coping strategies. Personality factors from the 16PF,
      Edwards's Personal Preference Schedule (Edwards, 1959), and the Jackson
      Personality Research Form (Jackson, 1984) were drawn into the same model to
      explain and predict both typical (actually occurring) and stereotypical (expected
      or assigned) sex differences in motivation and emotion. Data from several
      experiments and a meta-analysis support the conclusion that the model can
      successfully predict sex differences and that although most differences tend to
      occur in the direction predicted by the model, typical sex differences are less
      frequent and of a smaller magnitude than stereotypical differences.

PMID- 8760496
TI  - Mothers: influential agents in father-child relations.
AB  - One hundred forty-four mothers and fathers completed structured, standardized
      questionnaires that assessed mother's personal characteristics (developmental
      history, responsiveness, and sex role orientation), contextual domains
      (satisfaction with marriage, employment status, and social support), maternal
      attitudes about the importance of and satisfaction with spouse's involvement in
      childrearing, maternal support for father's involvement, children's
      characteristics (age, sex, problem behaviors), and father's involvement and
      satisfaction. Results from analyses of variance showed that the age of the child
      and maternal support were the strongest predictors of father's involvement and
      satisfaction, but ecological domains, maternal attitudes, mothers' personal
      attributes, and children's characteristics also contributed reliably to
      variations in fathering.

PMID- 8760497
TI  - Psychoneuroimmunology: searching for the main deteriorating psychobehavioral
      factor.
AB  - Psychoneuroimmunology has become an independent science with a broad experimental
      basis. However, its theoretical basis is still very vague and ambiguous. There
      are many contradictions in the experimental data that have not been integrated
      into a united conception, and some accepted paradigms that remain doubtful. The
      present critical review suggests a conceptual approach to the problem based on
      the proposition of two opposite types of behavior (search activity and
      renunciation of search) with attempts to integrate experimental results by
      avoiding contradiction. The analysis of the literary data confirms that every
      behavior that includes search activity prevents psychoimmunological disorders,
      whereas renunciation of search displays a general predisposition to such
      disorders. Such an approach makes possible new solutions of paradoxes and
      broadens the possible interpretations of the alteration of immune functions in
      depression, anxiety, and stressful events.

PMID- 8760498
TI  - The 2.8 A structure of a T = 4 animal virus and its implications for membrane
      translocation of RNA.
AB  - Simple RNA animal viruses generally enter cells through receptor-mediated
      endocytosis followed by acid pH dependent release and translocation of RNA across
      the endosomal membrane. The T = 3 nodaviruses contain prefabricated pentameric
      helical bundles that are cleaved from the remainder of the subunits by an
      assembly-dependent auto-proteolysis and they are positioned for release through 5
      fold axes of the particle. We previously proposed that these bundles may serve as
      conduits for RNA membrane translocation. Additional support for this hypothesis
      is now provided by the first atomic resolution structure of a T = 4 RNA virus,
      where we find cleavage sites and helical bundles nearly identical with those
      observed in T = 3 nodaviruses. The helices are of sufficient length to span a
      membrane bilayer and the internal diameter of the coiled bundle could accommodate
      ssRNA. The T = 4 particle has a mean outer diameter of 410 A and is formed by 240
      copies of a single subunit type. The subunit is composed of a helical inner
      domain (where the cleavage occurs) containing residues preceding and following a
      canonical, viral, eight-stranded beta-sandwich that forms the contiguous shell.
      Inserted between two strands of the shell domain are 133 residues with an
      immunoglobulin c-type fold. The initial gene product consists of 644 amino acid
      residues and is cleaved between residues Asn570 and Phe571 in the mature particle
      determined in this analysis.

PMID- 8760499
TI  - Peptide libraries define the fine specificity of anti-polysaccharide antibodies
      to Cryptococcus neoformans.
AB  - Cryptococcus neoformans is an encapsulated fungus that causes a life-threatening
      meningoencephalitis in patients with AIDS. Monoclonal antibodies to the capsular
      glucuronoxylomannan can modulate the infection in mice, but the epitopes on this
      complex polysaccharide recognized by protective and non-protective antibodies
      have not been defined. We have used 2H1, one of our most protective antibodies,
      to screen phage display peptide libraries for peptide mimotopes that would allow
      us to explore the fine specificity of anti-cryptococcal polysaccharide
      antibodies. Hexa- and decapeptides have been identified with sequence homologies
      that define four motifs: 1, (E)TPXWM/LM/L; 2, W/YXWM/ LYE; 3, DWXDW; and 4,
      (Ar)WDGQ(Ar). Peptides representing these motifs compete with each other for a
      shared binding site that overlaps the polysaccharide binding site. Motifs 1 and 2
      confer high affinity binding, and PA1, which displays a motif 1 peptide with the
      sequence LQYTPSWMLV, binds to 2H1 with a Kd of 295 nM. Analysis of the
      interaction between the 2H1 binding peptides and 24 structurally related anti
      polysaccharide antibodies reveals a complex pattern of reactivity that strongly
      suggests binding to or close to the complementary determining regions.
      Furthermore, those antibodies that have been shown to have different specificity,
      and in some cases different protective potential, do not bind any of the peptides
      selected by the protective 2H1 antibody. This study shows that peptide mimotopes
      for a complex microbial polysaccharide can be identified by screening phage
      peptide libraries and demonstrates the usefulness of such peptides in analyzing
      closely related interactive sites of proteins in general and of antibodies in
      particular.

PMID- 8760500
TI  - Analysis of the CYT-18 protein binding site at the junction of stacked helices in
      a group I intron RNA by quantitative binding assays and in vitro selection.
AB  - The Neurospora crassa mitochondrial tyrosyl-tRNA synthetase (CYT-18 protein)
      functions in splicing group I introns by promoting the formation of the
      catalytically active structure of the intron RNA. Previous studies showed that
      CYT-18 binds with high affinity to the P4-P6 domain of the catalytic core and
      that there is some additional contribution to binding from the P3-P9 domain.
      Here, quantitative binding assays with deletion derivatives of the N. crassa
      mitochondrial large rRNA intron showed that at least 70% of the binding energy
      can be accounted for by the interaction of CYT-18 with the P4-P6 domain. Within
      this domain, P4 and P6 are required for high affinity CYT-18 binding, while the
      distal elements P5 and P6a may contribute indirectly by stabilizing the correct
      structure of the binding site in P4 and P6. CYT-18 binds to a small RNA
      corresponding to the isolated P4-P6 domain, but not to a permuted version of this
      RNA in which P4-P6 is a continuous rather than a stacked helix. Iterative in
      vitro selection experiments with the isolated P4-P6 domain showed a requirement
      for base-pairing to maintain helices P4, P6 and P6a, but indicate that P5 is
      subject to fewer constraints. The most strongly conserved nucleotides in the
      selections were clustered around the junction of the P4-P6 stacked helix, with
      ten nucleotides (J3/4-2,3, P4 bp -1 and 3, and P6 bp -1 and 2) found invariant in
      the context of the wild-type RNA structure. In vitro mutagenesis confirmed that
      replacement of the wild-type nucleotides at J3/4-2 and 3 or P4 bp-3 markedly
      decreased CYT-18 binding, reflecting either base specific contacts or indirect
      readout of RNA structure by the protein. Our results suggest that a major
      function of CYT-18 is to promote assembly of the P4-P6 domain by stabilizing the
      correct geometry at the junction of the P4-P6 stacked helix. The relatively large
      number of conserved nucleotides at the binding site suggests that the interaction
      of CYT-18 with group I introns is unlikely to have arisen by chance and could
      reflect either an evolutionary relationship between group I introns and tRNAs or
      interaction with a common stacked-helical structural motif that evolved
      separately in these RNAs.

PMID- 8760501
TI  - Conformational states bound by the molecular chaperones GroEL and secB: a hidden
      unfolding (annealing) activity.
AB  - We have analysed the conformational states of barnase that are bound by the
      molecular chaperones GroEL and SecB. Line broadening in the NMR spectra of
      barnase in the presence of chaperone indicates binding of the native state of
      barnase to both GroEL and SecB, with a dissociation constant of > 3 x 10(-4) M
      for the GroEL-native barnase complex. GroEL and SecB catalyse the hydrogen
      deuterium exchange of amide proteins of barnase that require global unfolding for
      exchange to occur, indicating that both chaperones bind to a fully unfolded state
      of barnase. Binding of the denatured state was also detected by a reversible
      lowering of the melting temperature of barnase in the presence of chaperone. The
      dissociation constant of the complex between denatured barnase and either
      chaperone is 5 x 10(-8) M. The chaperone-bound fully unfolded state is a minor
      conformation that would not be seen by direct observation under physiological
      conditions, as the folding intermediate of barnase is the most populated state in
      the complex. The rate-limiting step for exchange of buried amide protons of bound
      barnase is the unfolding of the folding intermediate, which is retarded > 2000
      fold in the complex with GroEL. The reverse refolding step is retarded > 1000
      fold by GroEL leading to an EX1 mechanism for exchange. In contrast, unfolding of
      native barnase is catalysed by > 1000-fold. Thus, molecular chaperones GroEL and
      SecB have the potential to act in vivo and in vitro as: (1) a folding/transport
      scaffold to prevent aggregation of partially folded states by binding; (2) as an
      annealing-machine to generate continuous unfolding of misfolded states until a
      low-affinity state is formed; and (3) as an unfoldase to catalyse unfolding of
      the misfolded states.

PMID- 8760502
TI  - Towards a molecular understanding of the elasticity of titin.
AB  - Vertebrate striated muscle behaves elastically when stretched and this property
      is thought to reside primarily within the giant filamentous protein, titin
      (connectin). The elastic portion of titin comprises two distinct structural
      motifs, immunoglobulin (Ig) domains and the PEVK titin, which is a novel motif
      family rich in proline, glutamate, valine and lysine residues. The respective
      contributions of the titin Ig and the PEVK sequences to the elastic properties of
      the molecule have been unknown so far. We have measured both the passive tension
      in single, isolated myofibrils from cardiac and skeletal muscle and the stretch
      induced translational movement of I-band titin antibody epitopes following
      immunofluorescent labelling of sites adjacent to the PEVK and Ig domain regions.
      We found that with myofibril stretch, I-band titin does not extend homogeneously.
      The Ig domain region lengthened predominantly during small stretch, but such
      lengthening did not result in measurable passive tension and might be explained
      by straightening, rather than by unfolding, of the Ig repeats. At moderate to
      extreme stretch, the main extensible region was found to be the PEVK segment
      whose unravelling was correlated with a steady passive tension increase. In turn,
      PEVK domain transition from a linearly extended to a folded state appears to be
      principally responsible for the elasticity of muscle fibers. Thus, the length of
      the PEVK sequence may determine the tissue-specificity of muscle stiffness,
      whereas the expression of different Ig domain motif lengths may set the
      characteristic slack sarcomere length of a muscle type.

PMID- 8760503
TI  - TcR recognition of the MHC-peptide dimer: structural properties of a ternary
      complex.
AB  - We have developed a method that utilizes site-specific mutation data, sequence
      analysis, immunological data and free-energy minimization, to determine
      structural features of the ternary complex formed by the T-cell receptor (TcR)
      and the class I major histocompatibility complex (MHC) molecule bound by peptide.
      The analysis focuses on the mouse Kd MHC system, for which a large set of clones
      with sequenced T-cell receptors is available for specific peptides. The general
      philosophy is to reduce the uncertainties and computation time in a free-energy
      minimization procedure by identifying and imposing experimental constraints. In
      addition to assessing compatibility with various kinds of immunological data, we
      are particularly interested in differentiating the structural features peculiar
      to this particular system from generic features, and in ascertaining the
      robustness of the structure; i.e. determining, in so far as possible, the
      variations in the structure that leave its compatibility with experiment
      unaltered from those that do not. This last is equivalent to recognizing that
      certain features of the model are presented with a reasonable degree of
      confidence, while others remain highly tentative. The central conclusion in the
      former category is a placement of the TcR on the Kd peptide complex, which has
      its beta 2, beta 3 and alpha 3 loops (i.e. the second and third complementarity
      determining region of the TcR beta chain, and the third complementarity
      determining region of the alpha chain) covering the peptide; the alpha 1 and
      alpha 2 loops covering the MHC alpha 1 helix; the alpha 2 loop interacting with
      residues on the MHC beta sheet; and the beta 1 and (part of) the beta 2 loops
      covering the alpha 2 MHC helix. More specifically, our findings include the
      following. (1) A highly conserved histidine residue in the first complementarity
      determining region of the TcR beta chain (beta:CDR1) points outward and interacts
      with highly conserved side-chains on the MHC alpha 2 helix. (2) The amino
      terminal portion of the beta 2 loop interacts with the carboxyl portion of the
      peptide. A particularly important interaction is K4 of the loop interacting with
      E8 of the peptide. (3) Charged side-chains of the 11-residue TcR alpha 2 loop
      interact with conserved charged side-chains at positions 44, 58, 61 and 68 on the
      MHC. (4) The TcR beta 3 loop interacts with the amino-terminal part of the
      peptide, up through position 4. (5) the TcR alpha 3 loop interacts with the
      central portion of the peptide and stacks against the beta 2 loop. (6) Because of
      the interaction between the beta 2 loop and the peptide, and stacking of beta 2
      on alpha 3, alpha 3 gene and V beta gene selection can be correlated. (7) Using
      the topology of the recently solved TcR alpha chain we predict that the alpha 2
      loop interacts with the loop on the MHC beta sheet floor, which encompasses
      residues 42 to 44.

PMID- 8760504
TI  - [Blood lipid parameters in smelters chronically exposed to heavy metals].
AB  - A group of 120 male workers, employed in copperworks (mean age = 41.5 years; mean
      exposure duration = 17,9 years) at workposts with the highest level of exposure
      to lead, were covered by the study. Blood levels of the following heavy metals
      were measured in all workers: Pb, Cd, Mn, Cu, Zn, Ca, Mg as well as
      concentrations of FEP and GSH, SOD activity in erythrocytes, parameters of lipid
      metabolism: total cholesterol, HDL2- HDL3-cholesterol, triglycerides, lipid
      peroxides (LPO), and lecithin-cholesterol acyltransferase (LCAT) activity. Mean
      blood lead level accounted for 251,86 micrograms/l, and mean level of FEP was
      slightly above normal. That may indicate moderate lead deposits in smelters.
      Concentrations of other metals remained within normal limits. No significant
      disturbances in lipid metabolism were observed. Along with expected positive
      correlation between lead blood level and FEP, a significant negative correlation
      between lead and cholesterol levels as well as between FEP and serum cholesterol
      was found. Moreover, a significant negative correlation between FEP and serum
      LPO, as well as a significant positive correlation between concentration and HDL2
      cholesterol level and between FEP concentration and SOD activity in erythrocytes
      were noted. We believe that unexpected outcome of our investigations could result
      from the adaptation of healthy smelters to the environmental conditions. It is
      assumed that further exposure could weak antioxidant mechanisms and lead, in
      consequence, to the manifestation of symptoms induced by harmful effect of free
      radicals.

PMID- 8760505
TI  - [Evaluation of magnesium, zinc, copper and calcium levels in workers exposed to
      organic solvents, hydrogen cyanide and harmful physical factors].
AB  - The aim of the work was to assess te effect of chronic occupational exposure to
      organic solvents, hydrogen cyanide, and harmful physical factors (noise,
      vibration and electromagnetic fields) on intra- and extracellular concentration
      of magnesium, zinc, copper and calcium. The study converted 83 persons (25 males
      and 57 females), aged 20-58 years (median: 37.8 +/- 8.64), employed in the MERA
      PAFAL SA Factory of Measuring Equipment, Swidnica, for 0.42 +/- 34 years (median:
      11.84 +/- 9.28). The subjects were divided into four groups: Group A-25 persons
      exposed to organic solvents; Group B-24 persons exposed to hydrogen cyanide;
      Group C-19 persons exposed to noise and vibration; and Group D-8 persons exposed
      to electromagnetic fields. Blood samples (10 ml) were collected from each person.
      Intra- and extracellular concentrations of magnesium, zinc, copper and calcium
      were estimated. CONCLUSIONS: exposure to 1) organic solvents induces depletion of
      calcium and zinc from the body and intracellular cumulation of magnesium; 2) to
      hydrogen cyanide induces depletion of intracellular zinc and intracellular
      cumulation of magnesium and zinc; 3) to noise and vibration induces depletion of
      calcium, zinc and copper and intracellular cumulation of magnesium; and 4)
      electromagnetic fields does not induce any significant changes in ionic
      concentrations.

PMID- 8760506
TI  - [Disturbances of glucose tolerance in workers exposed to electromagnetic
      radiation].
AB  - The study group was composed of 50 workers exposed to electromagnetic radiation
      (radiowaves). Out of them 31 persons (62%), employed mostly in the risk zone,
      showed irregular glycaemia after oral administration of 75 g of glucose. At
      normal blood sugar before breakfast, the glycaemia level was high following
      administration of glucose and it did not return to starting values after 2 hours.
      After 30 min from glucose administration the level accounted for 155 mg%, after
      60 min-180 mg%, after 90 min-153 mg% and after 120 min-124 mg%, on average. In 10
      persons (32%) with glucose tolerance disturbances, disorders in bioelectric
      activity of the brain (abnormal EEG record) were observed.

PMID- 8760507
TI  - [Objective evaluation of physical exertion in pregnant women based on long-term
      recording of heart action. Results of a pilot study].
AB  - The heart rate during whole day, periods of activity and sleep as well as
      repeatable daily activities were identified in a group of 22 women, aged 19-40,
      and pregnant for 12-36 weeks, following a 24-hour recording of the heart work. In
      four women only, mean circadian heart rate was under 87/min, a value considered
      as normal in moderate active persons. That indicates a significant pregnancy
      related increase of heart rate. A considerable great variation of heart rates was
      observed during a day. The highest heart rate (97-140/min) was caused by mounting
      the stairs; it was also noted during performing minor household jobs and/or
      preparing meals. While using transportation means, heart rate ranged from 78 to
      130/min, and at leisure form 89 to 108/min. It was found that the level of an
      acceptable load for women (100 heart beats/min) was already higher than the mean
      value for the whole period of activity. An analysis of the relationship between
      heart rate in certain situations and the age of women under study, and the
      pregnancy advancement, shows that heart rate was, in each period of recording,
      positively correlated with the women's age. That means an increasing, with age
      pregnancy-related load. Heart rate during a 24-hour period, periods of activity
      and sleep, during the use of transportation means, watching television and
      resting in a sitting position, was positively correlated with the duration of
      pregnancy. Negative correlation between heart rate and the duration of pregnancy
      was observed while mounting the stairs, preparing meals and performing other
      household jobs. The negative correlation indicates that the pace of activities
      performed can be easily regulated, and thus, the load magnitude adjusted to
      physical abilities, whereas the positive correlation indicates that such a
      possibility does not exist in regard to the expenditure of energy (work pace). To
      sum up, the data presented shows that the use of transportation means increased
      the women's load but they could easily perform minor household jobs. However,
      there were no occupationally working women in the study group, it can be
      concluded that this kind od analysis, and conclusions drawn, can be used in
      identifying types of work and workplaces which pose too much load to pregnant
      women.

PMID- 8760508
TI  - [Evaluation of selected parameters of circulatory system function in various
      occupational groups exposed to high frequency electromagnetic fields. II.
      Electrocardiographic changes].
AB  - The effect of electromagnetic fields (EMF) on the circulatory and nervous systems
      has been the subject of great interest for many years, since electric impulses
      generated in these systems by outer electric and magnetic fields can
      theoretically disturb their functions. The only data on chronic effect of weak
      EMFs on the human body come from the studies carried out in the Soviet Union
      between the fifties and the seventies. In view of a growing number of persons
      exposed to EMF, there is an urgent need for verifying those data by means of
      modern diagnostic methods. That is the reason why our study of the EMF effect on
      the circulatory system has been initiated. It covered 71 workers at four AM
      broadcast stations, 40 workers at ten radio link stations and 42 workers at three
      radioservices. Workers' exposure to EMF was evaluated (see part I). Subjective
      and objective medical examinations were performed in all workers in order to
      assess their state of health, then resting electrocardiogram, Holter
      measurements, and high intensity ECG were taken, and variation in cardiac rhythm
      was analysed by a long-term recording of blood pressure. The results of the
      analysis of the questionnaire survey as well as the Holter and resting ECG
      examinations are presented. The study indicated that exposure to EMF in
      parameters found in AM broadcast station increased risk for electrographic
      disturbances (detected by means of resting ECG and a 24-hour Holter recording) by
      six times in comparison with that in radio link station workers not exposed to
      medium wave EMF. In radioservice workers this risk was twice as high as that in
      link station workers. It seems that in AM broadcast station workers, resting ECG
      should be complemented by a 24-hour Holter measurements, particularly, if workers
      complain of the circulatory system disturbances.

PMID- 8760509
TI  - [Thyroid function in smelters after long-term exposure to heavy metals].
AB  - In the year 1995 in a group of 93 male workers of a copper smelter (mean age =
      40,7 years, exposure time = 8,5 years) following parameters were measured: blood
      levels of: lead and cadmium; serum levels of copper, zinc, calcium and magnesium
      with use of atomic absorption spectrophotometry; FEP-with Piomelli's method; and
      T3, T4 and TSH in serum with radioimmunometric method. Mean blood lead level was
      38,2 micrograms/dl, and concentrations of other metals and hormones were within
      norm limits. Mean level of FEP was slightly above norm (FEP = 106,5
      micrograms/100 ml E). We found no correlation between investigated hormones (T3,
      T4 and TSH) and age, length of exposure nor blood lead level. We found a
      significant inverse correlation between FEP and TSH (r = -0,207; p < 0,047). This
      correlation could point to the fact that lead burden (expressed not in the actual
      blood level but in the FEP concentration) could negatively influence endocrine
      functions through hypothalamic-pituitary axis.

PMID- 8760510
TI  - [Bronchial asthma with inflammation of the nose mucous membrane induced by
      occupational exposure to methyl methacrylate in a dental technician ].
AB  - A case report of a 40-year-old female dental technician with a 13-year history of
      methyl methacrylate exposure is presented. Symptoms of dyspnea, wheezing,
      coughing and rhinorrhea occurred 6-8 months after the first occupational contact
      with methyl-methacrylate containing substances. Skin tests performed with a
      battery of common allergens produced negative results. While performing a
      provocation test with methyl-methacrylate, the patient developed severe stridor
      and dyspnea with concomitant decrease in I second forced expiratory volume (FEV1)
      and peak respiratory flow (PEF). The increase in leukocytes, eosinophils,
      basophils, albumin, eosinophil cationic protein (ECP) and mast cell tryptase
      occurred in nasal lavage fluid after bronchial provocation test. The authors
      conclude that methyl-methacrylate may cause asthma (probably non-atopic) in
      persons occupationally exposed to its effect.

PMID- 8760511
TI  - [Quality assurance in occupational health services].
AB  - The general conditions influencing the quality assurance and audit in Polish
      occupational health services are presented. The factors promoting or hampering
      the implementation of quality assurance and audits are also discussed. The major
      influence on the transformation of Polish occupational health services in exorted
      by employers who are committed to cover the costs of the obligatory prophylactic
      examination of their employees. This is the factor which also contributes to the
      improvement of quality if services. The definitions of the most important terms
      are reviewed to highlight their accordance with the needs of occupational health
      services in Poland. The examples of audit are presented and the elements of
      selected methods of auditing are suggested to be adopted in Poland.

PMID- 8760512
TI  - [Clinical picture of vibration syndrome and diagnostic principles].
AB  - The author discussed health effects of occupational exposure to local vibration,
      taking into account classification of a clinical manifestation of vibration
      syndrome and its symptoms. The principles of subjective and objective evaluations
      of workers occupationally exposed to mechanical vibrations were laid down as well
      as conditions for correct diagnosis of vibration syndrome.

PMID- 8760513
TI  - [Combined biological effect of electromagnetic fields and chemical substances
      (toxic)].
AB  - The authors present results of own measurements and examinations as well as the
      literature data on the occurrence and effect of direct, low and high frequency
      electromagnetic fields and chemicals. In real working conditions and in
      experimental conditions, the following relations can be observed: 1) concomitant
      occurrence of electromagnetic fields and chemicals, e.g. processes of
      electrolysis, inductive and dielectric heating; 2) experimental studies of
      combined effect of electromagnetic fields and chemicals on e.g. cancer
      development: 3) drug effect modified by electromagnetic fields; 4) effect of
      chemicals produced in materials under the influence of electromagnetic fields.
      There are only a few publications on medical examinations of workers exposed
      simultaneously to electromagnetic fields and chemicals. However, even in those
      reported studies, an attempt to distinguish changes in the health state due to
      electromagnetic fields, and due to chemicals has field. The studies of the effect
      of electromagnetic fields which modify the effect of carcinogenic substances have
      not yielded unequivocal results. Electromagnetic fields may modify significantly
      the effect of some psychotropic and hormonal drugs. Under the influence of
      pyrolisis, induced by thermal effect of electromagnetic fields, toxic substances
      or substances with harmful biological effect may occur in some materials.

PMID- 8760515
TI  - [It should be obvious to everyone].

PMID- 8760514
TI  - [Use of low temperature methods with optically stimulated luminescence for
      measuring ionizing radiation doses].
AB  - A new method of cooled optically stimulated luminescence (COSL) based on CaF2:Mn
      crystals has become the subject of numerous studies carried out by the Pacific
      Northwest Laboratory in the United States. The method has developed and expanded
      the feasibility of measuring ionizing radiation doses based on a classical
      phenomenon of thermoluminescence. Much greater sensitivity of the new method
      allows to measure doses of 10 microR order. A manifold reading of a given
      dosimeter is also feasible. That facilitates the elimination of doubtful
      readings. The reading of a dose from the dosimeter and cleaning for its reuse is
      performed in temperatures not higher than room temperature. Therefore, dosimeters
      in the form of powder embedded in a plastic matrix which imitates live tissue,
      can be easily used, whereas thermoluminescence method would cause melting of a
      dosimeter during its reading. The authors made an attempt to get acquainted the
      reader with extremely interesting method for measuring ionizing radiation doses.

PMID- 8760516
TI  - [Prevention of cystic fibrosis?].

PMID- 8760517
TI  - [A follow-up study of carriers of cystic fibrosis].
AB  - The aim of the present study was to assess the long-term impact of carrier
      screening for cystic fibrosis. The impact of being identified as a carrier for
      cystic fibrosis was assessed through three questionnaires measuring the emotional
      responses, changes in reproductive attitudes and decisions, retention of the
      result, and sharing of the information about the result with relatives. The
      questionnaires were sent to 160 women identified as carriers between 1990 and
      1992 and to 200 randomly selected women with a negative result. Carriers became
      surprised, anxious and worried upon receipt of their result. However, this
      response disappeared once the partners had been tested and found negative. No
      sign of residual anxiety was found among carriers who answered the third
      questionnaire in November 1994. Carriers freely shared the information about
      their result with relatives, friends, and general practitioners. Few carriers
      changed their reproductive plans or attitudes to abortion of a foetus with CF due
      to the result. No decline in fertility or change in reproductive pattern were
      observed among carriers after testing. The imperfect sensitivity of the carrier
      test caused some misunderstanding in the retention of the result. This may
      reflect inadequacies in the information and counselling. Psychological factors
      are also believed to contribute to the misunderstanding of the result. The
      information should be improved to avoid false reassurance.

PMID- 8760518
TI  - [Control of the myocardial pump function during cytostatic treatment with
      anthracycline].

PMID- 8760519
TI  - [Left ventricular diastolic function assessment by transthoracic Doppler
      echocardiography].
AB  - Left ventricular diastolic dysfunction is currently recognized in patients with
      different heart diseases. Three abnormal filling patterns of the left ventricle
      detected by pulsed-Doppler echocardiography are observed in patients with heart
      disease. Each filling pattern is characterised by different symptoms, and by
      differences in function and dimension of the left atrium and filling pressures.
      Mitral and pulmonary venous flow velocities and durations obtained by pulsed
      Doppler technique can be used to evaluate left ventricular diastolic function in
      patients with different heart diseases. However, several factors affect the
      transmitral and pulmonary venous flow such as age, heart rate, positioning of the
      sample volume and aortic- and mitral valve insufficiency. These factors must be
      taken into consideration when the diastolic function is evaluated by pulsed
      Doppler technique.

PMID- 8760520
TI  - [Cocaine abuse and mental disease].
AB  - The comorbidity between psychiatric diseases and cocaine abuse is extensive.
      Several studies show that the prevalence of specific personality disorders,
      eating disorders, attention-deficit-disorder and affective disorders is high in
      cocaine abusers. Excessive cocaine consumption can lead to a toxic schizophrenic
      psychosis. The comorbidity has been understood in several ways, using many
      theoretical approaches. The different hypotheses should not be considered
      contradictive. Explanations involving genetic, psychosocial, psychological and
      biological approaches are necessary for a complete understanding of the
      comorbidity.

PMID- 8760521
TI  - [Diagnosis of suspected thoracic aortic dissection. Focused on transesophageal
      echocardiography].
AB  - Over a five-year period (1990-1994), 72 consecutive patients were referred to
      transoesophageal echocardiography (TEE) on suspicion of thoracic aortic
      dissection. TEE was performed as the only or last investigation in 42 patients
      (58%). In 44 patients one or more other investigations were carried out before
      final clinical decision making: aortography (n = 30), X-ray computer tomography
      (CT, n = 18), and magnetic resonance imaging (MRI, n = 12). The final diagnosis
      was based on the combination of clinical information, the available examination
      results, and findings at surgery or autopsy; 31 of the patients were diagnosed as
      having aortic dissection. One patient with aortic dissection died during TEE
      while none of the other patients suffered major complications. The sensitivity
      (demonstration of dissection including correct classification in type A or B) was
      81%, 80%, 45%, and 83% for TEE, aortography. CT, and MRI, respectively. The
      specificities were 88%, 93%, 71%, and 100%, respectively. Dissection of the
      thoracic aorta is a life-threatening condition demanding prompt and accurate
      diagnosis. None of the four techniques employed in the present study is ideal.
      Although TEE is adequate for immediate bedside examination our results show that
      more time-consuming and resource demanding investigations are sometimes required.
      Proper training and improved equipment may, however, increase the usefulness of
      TEE in patients with suspected aortic dissection.

PMID- 8760522
TI  - [Emergency care during ambulatory vasectomy].
AB  - We describe a case of cardiac arrest during outpatient vasectomy. The possible
      mechanisms and need for monitoring are discussed. We recommend that the surgeon
      should be able to provide basic life support during outpatient vasectomy. Routine
      electronic monitoring during and after the procedure is probably not warranted
      and should at least await clinical studies on cardiac function and morbidity
      during and after the procedure.

PMID- 8760523
TI  - [Everything is as before].

PMID- 8760524
TI  - [Factor V Leiden mutation].

PMID- 8760525
TI  - Ultrasound training during ATLS: an early start for surgical interns.
AB  - OBJECTIVES: Determine if: (1) surgical interns could learn essential ultrasound
      principles of the focused assessment for the sonographic examination of the
      trauma patient (FAST) during Advanced Trauma Life Support (ATLS), and (2) swine
      are adequate models for learning the FAST. DESIGN: Lecture, videotape,
      pre/posttests, and practical examination. METHODOLOGY: Day 1: Survey, pretest,
      lecture, and videotape. Day 2: Three swine, used in ATLS, had diagnostic
      peritoneal lavage catheters reinserted to infuse fluid and produce "positive"
      ultrasound examinations. Two fresh swine were "negatives"; however, all five
      swine were draped similarly to disguise interventions. Interns were tested
      individually by surgeon-sonographers to determine whether the ultrasound image
      was "positive" or "negative." Posttests were completed while surgeons performed
      postmortem examinations on two swine. STATISTICS: Paired Student's t test and
      Wilcoxon Rank Sum test. RESULTS: Survey (5 min): 48% had exposure to ultrasound.
      Relationship of test scores showed no significant difference (p = 0.46 to 0.91)
      between interns with and without ultrasound experience. Tests (30 min): Mean pre-
      and posttests scores = 65.6 and 90.8, respectively (p < 0.001). Practical
      examination (140 min): Mean score = 89.6. Postmortem examinations: Left hepatic
      lobe partially obscured the spleen. CONCLUSIONS: (1) Surgical interns can learn
      essential ultrasound principles of the FAST during ATLS (2) Swine are feasible
      models for learning the FAST.

PMID- 8760526
TI  - Rupture of the pathologic spleen: is there a role for nonoperative therapy?
AB  - INTRODUCTION: While nonoperative management of blunt splenic injury in the stable
      patient has become the standard of care, splenectomy is still advocated as the
      safest management for rupture of the diseased spleen. The combination of
      splenectomy and underlying immunosuppression may render these patients
      particularly susceptible to postsplenectomy infection, and thus we undertook a
      prospective trial of nonoperative management of the ruptured pathologic spleen.
      METHODS: Hemodynamically stable patients with preexisting pathologic splenomegaly
      and isolated splenic disruptions diagnosed by computed tomographic (CT) scan
      (American Association for the Surgery of Trauma (AAST) grades 1-4) requiring 2 or
      less units blood transfusion were prospectively studied. Patients were monitored
      in a critical care setting, and resolution of splenic disruption was followed by
      serial CT examinations. RESULTS: Nonoperative management was successful in all 11
      patients (eight, HIV/AIDS; one each, acute leukemia, infectious mononucleosis,
      sickle cell anemia). The mean transfusion requirement was 0.7 units; the mean
      length of stay was 16 days. CONCLUSIONS: The pathologic spleen can heal after
      parenchymal disruption. While not appropriate for all patients, a subset of
      hemodynamically stable patients can be successfully managed nonoperatively using
      CT diagnosis, close clinical monitoring, and minimal transfusions.

PMID- 8760527
TI  - Conservative treatment of copperhead snakebites without antivenin.
AB  - Polyvalent antivenin remains the most recommended treatment of crotalid
      envenomation, including copperhead snakebites. Because of the significant
      morbidity associated with antivenin therapy, some have proposed conservative
      therapy for less serious envenomations. Few if any studies have separated the
      treatment of the less serious copperhead bite from the more serious bite of a
      rattlesnake or a water moccasin. Fifty-five patients, including 12 children, with
      copperhead bites were treated over a 12-year period. All 55 patients were
      successfully treated conservatively without antivenin. Conservative treatment
      resulted in no deaths, limb loss, or residual disability. The mean hospital stay
      was 2.15 days compared with 3.9 days in patients with systemic symptoms. These
      data support a conservative approach to most copperhead envenomations and suggest
      that the treatment for copperhead bites should be segregated from the more
      serious rattlesnake and water moccasin snakebites.

PMID- 8760528
TI  - Induction of cytokine-induced neutrophil chemoattractant (CINC) mRNA in the lungs
      of septic rats.
AB  - OBJECTIVE: To study cytokine-induced neutrophil chemoattractant (CINC) mRNA
      induction in lungs of normal, neutropenic, and adrenalectomized rats after
      intraperitoneal Escherichia coli lipopolysaccharide (LPS) administration and in
      cultured rat pulmonary cell lines after exposure to mediators of the septic
      response. MATERIALS AND METHODS: Northern blotting was used to assay relative
      CINC mRNA levels and a colorimetric myeloperoxidase assay was used as a measure
      of neutrophil infiltration. RESULTS: After a single dose of LPS, rapid induction
      of CINC mRNA coincided with neutrophil infiltration into lungs, a response that
      lasted approximately 12 to 24 hours. Multiple LPS treatments resulted in a
      similar CINC response, but a more prolonged myeloperoxidase response. CINC mRNA
      induction in lungs was heightened 30% in adrenalectomized animals and 400% in
      neutropenic ones. LPS and cytokines induced CINC mRNA in cultured endothelial and
      epithelial cells. CONCLUSIONS: Induction of CINC mRNA expression in pulmonary
      endothelial and/or epithelial cells by systemic LPS or cytokines may play a role
      in mediating neutrophil infiltration into lungs during sepsis. Markedly increased
      CINC induction in the lungs of neutropenic animals suggests that neutrophils may
      act to inhibit expression of this chemoattractant via a negative feedback
      mechanism.

PMID- 8760529
TI  - Prophylactic Greenfield filters: acute complications and long-term follow-up.
AB  - The efficacy of prophylactic vena caval filters (VCF) in reducing morbidity and
      mortality from pulmonary embolism (PE) in high-risk trauma patients has been
      shown, but minimal follow-up data is currently available. VCFs were
      prophylactically placed in 110 patients between August 1991 and June 1995. There
      was an early VCF complication rate of 7%. Twenty-two patients died; the remaining
      88 patients formed the basis for the follow-up study. Forty-five patients were
      located and interviewed by phone, and 30 of these patients (34%) returned for
      evaluation. The mean follow-up time was 18 months (range, 4-42 months). There was
      no incidence of caval thrombosis on follow-up. Eleven patients had physical
      findings, and duplex evidence consistent with postphlebitic syndrome. An
      additional three patients had evidence of old deep venous thrombosis (DVT) by
      duplex, but no significant symptomatology. VCF are effective in preventing PE
      related deaths and have few major complications. The long-term morbidity
      associated with posttraumatic venous thrombosis is significant. This morbidity is
      related not to PE or VCF, but to the underlying DVT. Improved strategies against
      DVT are necessary.

PMID- 8760530
TI  - Percutaneous dilational tracheostomy: report of 356 cases.
AB  - OBJECTIVE: To evaluate the procedure time, complications, and percutaneous
      dilational tracheostomy (PDT) charges. DESIGN: Operative data were prospectively
      collected for 356 PDTs including the initial series of 141 PDTs reported in 1994.
      Short- and long-term complications were retrospectively identified by review of
      medical records and patient telephone interviews. MATERIALS AND METHODS: PDT was
      performed using the "Ciaglia" method of serial dilation over a Seldinger
      guidewire. Discharged patients (n = 258) were followed for a mean (+/-SD) of 10
      +/- 7 months. MEASUREMENTS AND MAIN RESULTS: The mean procedure time was 15 +/- 8
      minutes; operative mortality rate, 0.3% (1/356); overall complication rate, 19%
      (69/356); long-term symptomatic tracheal stenosis rate, 3.7% (8/214). The mean
      total patient charge for bedside PDT was $1,370; for open tracheostomy in the
      operating room, $2,675. CONCLUSIONS: Surgeons can rapidly perform PDT at the
      bedside with a lower risk of complications than open tracheostomy and at a
      significantly reduced patient charge.

PMID- 8760531
TI  - Percutaneous versus open tracheostomy: a retrospective cohort outcome study.
AB  - Percutaneous tracheostomy has been advocated as a faster, safer, and less
      invasive method of placing tracheostomy tubes in ventilated patients. To compare
      outcome differences, as measured by complication rates, between percutaneous and
      open tracheostomy, a retrospective cohort study was performed. All procedures
      were performed in the intensive care unit of a university-affiliated hospital.
      The minor complication rates did not differ significantly between percutaneous
      and open tracheostomy (12/31 vs. 12/29, respectively; p > 0.05), nor did there
      appear to be a difference in rates of major complications between the two groups
      (7/31 vs. 5/29; p > 0.05). This study identified a trend towards an increased
      risk of delayed airway loss in the percutaneous tracheostomy group.

PMID- 8760532
TI  - Human immunodeficiency virus and the trauma patient: factors influencing
      postoperative infectious complications.
AB  - OBJECTIVE: While immunosuppression 2 degrees to human immunodeficiency virus
      (HIV) infection should logically render HIV+ trauma victims more prone to
      infection after injury, little data is available regarding trauma outcome in this
      group of patients. Since the helper CD4+ lymphocyte count is a marker for
      progression of HIV-associated diseases, we examined the relationship between CD4+
      counts, Injury Severity Score (ISS), and bacterial infectious complications in
      HIV+ trauma patients. METHOD: Retrospective review of 56 consecutive HIV+ trauma
      patients treated at a Level I trauma center. RESULTS: Nine patients (15%)
      developed significant infectious complications (four pneumonias, three soft
      tissue infections, one urinary tract infection, one wound infection) with no
      pattern to the causative agents. Evaluation of CD4+ counts, white blood cell
      counts, serum albumin levels, blood transfusion requirements, and ISS revealed
      that only the ISS was associated with infectious complications. CONCLUSION:
      Despite the profound immunosuppression in this group of patients, the incidence
      of bacterial infectious complications was independent of the CD4+ count (p =
      0.958), but was associated with increases in the ISS (p = 0.003).

PMID- 8760533
TI  - Serious traumatic brain injury: an evaluation of functional outcomes.
AB  - OBJECTIVES: Evaluate independent living, productivity, and social outcomes of
      patients with serious traumatic brain injury (TBI) after inpatient
      rehabilitation. METHODS: Fifty-five adults with serious TBI (Abbreviated Injury
      Scale score > or = 3) were admitted to a Level I trauma center and subsequently
      transferred to a comprehensive inpatient rehabilitation hospital (Walton
      Rehabilitation Hospital). Functional Independence Measures were obtained at
      admission (Adm), discharge (D/C), and at 3- (n = 52) and 1-year (n = 51) follow
      up. RESULTS: At 1 year, 90% of the patients were living at home. Eight (16%)
      required full-time supervision, while 41 (82%) were independent of supervision
      throughout most of the day. Thirteen (25%) patients had returned to work, eight
      full time and five with reduced responsibility and fewer hours than before
      injury. Nineteen shared household duties, while eight (16%) had primary
      responsibility. Fourteen (27%) patients demonstrated socially inappropriate or
      disruptive behavior at least weekly. [table: see text] CONCLUSION: Although
      cognitive skills were diminished for the majority of patients, many achieved a
      substantial reduction in disability within 18 months after TBI.

PMID- 8760534
TI  - Trauma on the Internet: early experience with a World Wide Web server dedicated
      to trauma and critical care.
AB  - The Internet is the newest and one of the most powerful communications media
      today. This study evaluates the utility of dissemination of educational
      information and exchange of ideas related to trauma at a single site on the
      Internet. A World Wide Web server on a desktop computer provided a library of
      downloadable medical software, trauma prevention information, and patient case
      studies. RESULTS: Most server accesses came from connections at other educational
      institutions (29.6%). Connections by foreign clients accounted for 17.9% of use.
      Over a 6-month period, the usage increased from an average of 80 files
      transmitted per day to 600 per day (750% increase). CONCLUSIONS: A trauma and
      surgical critical care related data server has shown a progressive increase in
      use in its initial period. Further development by other trauma care providers
      will be of value in educating the health care community and lay public.

PMID- 8760535
TI  - Colostomy in penetrating colon injury: is it necessary?
AB  - OBJECTIVE: To compare in a randomized prospective manner the complication rates
      associated with colostomy versus primary repair in penetrating colon injuries.
      METHODS: During a 38-month period, 114 patients with penetrating wounds of the
      colon were entered into a randomized prospective study at an urban Level I trauma
      center. The patients were randomized to a primary repair group or a diversion
      group. Randomization was completely independent of any risk factors, including
      number of abdominal organ systems injured, extent of fecal contamination, blood
      loss, presence of shock (systolic blood pressure < 80), time from injury to
      operation, and severity of colon injury. Five patients initially entered in the
      study died in the immediate postoperative period (< 24 hours) and were removed
      from the study because their deaths were unrelated to their colon injuries.
      RESULTS: A total of 109 patients were studied, of which 56 were randomized to
      primary repair and 53 to diversion (39 colostomies, 14 ileostomies). The average
      age for the primary repair group was 28.5 years and for the diversion group it
      was 26.8 years. The average Penetrating Abdominal Trauma Index for the primary
      repair group was 24.3 and for the diversion group it was 22.8. There were 11
      (20%) septic-related complications in the primary group versus 13 (25%) in the
      diversion group. Complication rates in the presence of significant fecal
      contamination, shock, significant blood loss (> 1000 mL), more than two organ
      systems injured and extent of colon injury were all higher in the diversion
      group. There was one mortality in the diversion group and two in the primary
      repair group. CONCLUSIONS: The authors conclude that all penetrating colon
      injuries in the civilian population should be primarily repaired.

PMID- 8760536
TI  - Missed injuries in abdominal trauma.
AB  - Injuries missed at initial diagnoses or operations have the potential to cause
      disastrous complications in abdominal trauma patients. The aim of this
      retrospective study is to assess the causes and the outcomes of missed abdominal
      injuries. Twelve patients (2%) with missed injuries were identified among 607
      abdominal trauma patients operated on from 1985 to 1993. Ten patients were male
      and two were female. The modes of the trauma were ten blunt injuries (83%) and
      two stab penetrating injuries (17%). Five cases had delayed operations because of
      clinical errors in the initial diagnosis. Their causative factors were obscured
      trauma history (two cases), radiologic misinterpretation (two cases), no reliable
      radiologic finding (one case), and admission to inappropriate department (one
      case). Missed injured organs were spleen (two cases), liver (one case), diaphragm
      (one case), and rectum (one case). Median delayed time was 7 days (3 to 96 days).
      Another seven cases of injuries were missed at the time of initial operation
      because of incomplete exploration. Their causative factors were surgical
      inexperience (two cases), severe peritoneal adhesions (one case), neglected
      exploration of retroperitoneal hematoma (two cases), underestimated mesocolic
      vascular injury (one case), and early contraction of the perforating wound with
      intraoperative hypotension (one case). Missed injured organs were stomach (two
      cases), duodenum (one case), rectum (one case), pancreas (one case), urinary
      bladder (one case), and rectosigmoid mesocolon (one case). Median time interval
      between initial and second operation was 9 days (4 to 32 days). Two patients died
      of complications directly related to their missed injuries. Major complication
      and mortality rates of missed injuries were 83 and 17%, respectively. These were
      significantly higher compared with those (39 and 6.3%, respectively) of detected
      abdominal injuries. We conclude that missed abdominal injuries can cause high
      mortality and morbidity, and, therefore, a systematic approach, including careful
      history taking, complete diagnostic procedure, complete surgical explorations,
      and early reoperation are mandatory for patients with multiple trauma.

PMID- 8760537
TI  - Small versus large diameter closed-section femoral nails for the treatment of
      femoral shaft fractures: is there a difference?
AB  - A retrospective series of 99 femoral shaft fractures treated by small diameter
      (10 and 11 mm) and large diameter (> 11 mm) closed section femoral nails from
      November 1989 to September 1993 was analyzed. No significant differences in the
      parameters of bony union and time to full weight bearing were seen between the
      two groups nor were there significant differences between the rate of secondary
      procedures. There were no broken nails in either group and there was no
      difference in the overall respiratory complication rate. CONCLUSION: No
      statistically significant differences existed between the small and large
      diameter groups except for the mean age and mean follow-up period. Small diameter
      nails can be used safely without the risk of nail breakage.

PMID- 8760538
TI  - Hemodynamic, plasma volume, and prenodal skin lymph responses to varied
      resuscitation regimens.
AB  - The theoretical efficacy of hypertonic saline (HS) resuscitation for hemorrhagic
      shock purportedly stems from the osmolar extraction of intracellular fluid into
      the plasma. This hypothesis presumes a concomitant expansion of the interstitial
      fluid space. Colloid resuscitation, in theory, expands the plasma volume by
      extracting interstitial fluid. These hypotheses were tested in a canine-modified
      Wigger's model of hemorrhagic shock. Forty, male, splenectomized dogs were
      anesthetized and instrumented. Animals underwent a baseline equilibration period
      followed by shock for 120 minutes. Each animal was randomized to one of four
      groups and received equal amounts of Na+ either as lactated Ringer's (LR)
      solution, 10% dextran 40 (Dex) in normal saline, 7.5% saline (HS), or 7.5% saline
      plus Dex (HSD). Parameters measured at baseline, shock, and at postresuscitation
      30 minutes, 60 minutes, 90 minutes, and 120 minutes, included: mean pressure
      (MAP), output, pulmonary capillary wedge pressure, prenodal skin lymph flow,
      serum and lymph albumin, wet-to-dry skin ratios, and plasma volume. MAP, cardiac
      output, and plasma volume were most quickly restored with LR and Dex
      resuscitation (MAP = 106 and 118 mm Hg) compared to HS and HSD (MAP = 98 and 92
      mm Hg). Lymph flow and lymph albumin flux were best restored with LR and HSD
      (mean = 85 and 48 microL/min) compared to Dex and HS (mean = 36 and 37
      microL/min). Wet/dry skin ratios were greatest at 60 minutes in the LR group but
      similar at 120 minutes in all four groups. These data suggest that interstitial
      fluid space remains contracted during the first hour after HS, HSD, and Dex
      resuscitation compared with LR resuscitation, even though the restoration of
      plasma volume, MAP, and cardiac output is greatest with the Dex regimen. Further
      studies with total body water and intracellular water are needed in this model.

PMID- 8760539
TI  - Platelet activating factor mediates cardiopulmonary dysfunction during graded
      bacteremic shock.
AB  - OBJECTIVE: To determine whether or not platelet activating factor (PAF) is a
      necessary mediator of cardiovascular dysfunction during graded bacteremia, and to
      identify PAF interactions with eicosanoids and tumor necrosis factor-alpha (TNF
      alpha). METHODS: Seventeen anesthetized, hemodynamically monitored adult swine
      were studied for 4 hours in three groups. Group 1 (ANES, n = 5) were anesthesia
      controls; group 2 (septic control, SC, n = 6) received intravenous Aeromonas
      hydrophila (109/mL) at rates incrementally increased from 0.2 to 4.0 mL/ kg/h;
      group 3 (WEB, n = 6) received the PAF receptor antagonist WEB 2086, 3.0 mg/kg
      intravenously, then A. hydrophila. Cardiopulmonary parameters and plasma
      thromboxane B2 (TXB2), prostaglandin 6-keto F1 alpha (PGI2), leukotriene B4
      (LTB4), leukotrienes C4D4E4 (LTC4D4E4), and TNF-alpha were measured hourly.
      Statistical analysis was carried out using two-way analysis of variance (ANOVA)
      for repeated measurements, Dunnett's t test, and Student's t test, where
      appropriate. Statistical significance was determined at the 95% confidence
      interval. Values are presented as the mean +/- SEM. RESULTS: Pulmonary arterial
      pressure, pulmonary capillary wedge pressure, central venous pressure heart rate,
      VO2 and O2ER decreased significantly after WEB 2086 infusion, compared with SC,
      and mean arterial pressure, systemic vascular resistance index, stroke volume
      index, and left ventricular stroke work index increased. Arterial pH decreased
      significantly in SC animals, but was maintained at normal levels during
      bacteremia in the WEB group. Differences between WEB and SC for cardiac index,
      pulmonary vascular resistance index, right ventricular stroke work index, PaO2,
      SaO2, and PcO2, were not significant. The addition of WEB 2086 significantly
      decreased plasma levels of TXB2, PGI2, LTB4, and TNF-alpha compared with the SC
      group. LTC4D4E4 was decreased in WEB compared with SC animals, in which LTC4D4E4
      increased during graded bacteremia. CONCLUSIONS: PAF is necessary to the
      development of systemic vasodilation and hypotension, pulmonary hypertension,
      decreased stroke volume, metabolic acidosis, and increased oxygen uptake during
      graded bacteremia. PAF-induced eicosanoid and cytokine release may be involved.

PMID- 8760540
TI  - Production of cytokines and prostaglandin E2 by subpopulations of guinea pig
      enterocytes: effect of endotoxin and thermal injury.
AB  - BACKGROUND: There is increasing evidence that cells other than immune cells have
      the potential for producing immunomediators. This study determined whether
      distinct populations of enterocytes from unburned and burned animals responded
      differently to endotoxin regarding production of tumor necrosis factor,
      interleukin-1 and -6 and prostaglandin E2. METHODS: Three subpopulations of
      enterocytes, progressing from the villus tip towards the crypt, were obtained
      from washes of the small intestine. The cells were cultured in the presence of
      endotoxin, and the supernatants were assayed for the mediators. RESULTS: Thermal
      injury primed all three populations of enterocytes to produce larger amounts of
      tumor necrosis factor and interleukin-6 compared to cells from unburned animals.
      Enterocytes that were nearer the crypt produced the largest amounts of the
      cytokines. CONCLUSION: These observations may be important because, as gut
      integrity is compromised after thermal injury, enterocytes that may have
      previously been unexposed or less exposed to endotoxin can become a significant
      source of inflammatory cytokines.

PMID- 8760541
TI  - Blunt cardiac injuries in children: a postmortem study.
AB  - We reviewed the records of the Chief Coroner for all pediatric (< 16 years of
      age) trauma fatalities in Ontario (pediatric population of 2 million) for the
      period January 1, 1988 through December 31, 1990. Forty-one (14.5%) of 282
      patients for which complete autopsy data were available had sustained cardiac
      injuries. Nineteen patients (46%) died at the scene of the accident, 15 patients
      (37%) died in an emergency department, and seven patients (17%) died during
      hospitalization. Rupture of a cardiac chamber occurred in 16 cases; it was the
      main cause of death in eight cases and a contributing factor in the remainder.
      Cardiac contusion without chamber rupture was present in 25 cases, but in none of
      the cases was it the cause of death. Brain injury was the cause of death in 16
      (64%) of the cases of cardiac contusion. Cardiac injuries are more common among
      children who die from blunt trauma than previous reports have suggested. However,
      because these injuries are often rapidly fatal, many patients die before they
      reach a hospital. With improvements in emergency medical services and the
      resulting reduction in transit time, more patients may reach trauma centers
      alive. A high index of suspicion and rapid diagnosis and treatment of these
      injuries can save the lives of some of these patients.

PMID- 8760542
TI  - Pediatric cervical spine injury: a three-year experience.
AB  - BACKGROUND: Traumatic injuries of the cervical spine are uncommon in pediatrics.
      Children less than 8 years of age are reported to have "exclusively" upper
      cervical injuries. Recent experience at The Children's Hospital of Alabama (TCHA)
      challenged both of these notions. METHODS: A concurrent retrospective chart
      review of all cervical spine injuries treated at TCHA between January 1, 1992 and
      December 31, 1994 was performed. Data collected included patient demographics,
      date and time of injury, mechanism and site of injury, presence of associated
      injuries, clinical management, and outcome. RESULTS: Thirty-four patients with
      cervical spine injuries were seen at TCHA in the 36-month study period. The
      leading mechanism of injury was motor vehicle crashes (23/34 or 68%). Head
      injuries were associated with cervical spine injury in 53% of patients. Of the 20
      patients aged 8 years or less, 10 (50%) had "low" cervical spine injuries (below
      C4). Overall mortality was 41% (14/34). Of the 15 vehicle occupants, 12 were
      unrestrained or inappropriately restrained. Two of those appropriately restrained
      were young school-aged children in lap-shoulder belts who sustained isolated
      cervical spine injuries. CONCLUSIONS: 1. The number of pediatric cervical spine
      injuries in our institution appears to be increasing. 2. Cervical spine injury in
      children less than 8 years of age are not exclusively confined to the region
      above C4. 3. Occurrence of cervical spine injuries despite lap-shoulder belt use
      suggests that efforts should be focused on refinement of motor vehicle restraint
      devices in young school-aged children.

PMID- 8760543
TI  - Fatal motor vehicle crashes: variations of crash characteristics within rural
      regions of different population densities.
AB  - OBJECTIVE: While it is known that motor vehicle crash (MVC) fatality rates are
      inversely related to population density, there has been no description of which
      crash variables are related to population density. The purpose of this study was
      to describe crash characteristics of fatal MVCs and to determine which crash
      characteristics are related to population density. DESIGN: This is a
      retrospective review of fatal accident reporting system (FARS) records. They
      represent four different population density regions over a 5-year period in a
      four-state midwest region. RESULTS: There were 10,932 people in 6,318 vehicles
      who were involved in 4,970 fatalities. Occupant fatality rates per 100,000
      persons were inversely related to population density. The variables related to
      lower population density were more light and heavy truck types, more frequent
      alcohol use and higher levels of intoxication, more frequent crashes that are
      noncollisions on less heavily traveled roads, more frequent crashes on gravel
      surface types, more frequent occupant ejection, and delayed medical care.
      CONCLUSION: Rural areas are not homogenous in terms of fatal MVC crash
      characteristics. By analyzing fatal MVC crash characteristics in regions with
      different population densities, many crash variables were found to be related to
      population density. By understanding which characteristics about fatal MVCs are
      related to population densities, different interventions could be targeted to
      different rural populations.

PMID- 8760544
TI  - Spectrum of injuries from snowboarding.
AB  - OBJECTIVE: To examine and compare the types, frequency, and associated risk
      factors of injuries sustained in snowboarders with downhill skiers. DESIGN:
      Prospectively administered survey. MATERIALS AND METHODS: All snowboarders and
      skiers who presented to a rural hospital emergency department in California
      during one winter season were asked to answer a survey eliciting information
      regarding participants' demographics, previous experience, equipment use and
      circumstances surrounding their injury. MEASUREMENTS AND MAIN RESULTS: An overall
      response rate of 87.4% yielded examination of 355 injured snowboarders. Victims
      tended to be male (81%) with a mean age of 19.8. Snowboarders were more likely to
      injure the upper limb than skiers (58% vs. 32%, respectively, p < 0.001) but less
      likely to injure the lower extremities (16% vs. 35%, p < 0.001). Wrist injuries
      were most common. Nonorthopedic injuries were less common but potentially life
      threatening. The data also suggest that aerial maneuvers are associated with
      increased risk of injury to the head, face, spine, and abdomen and that
      collisions are associated with more severe injury. Snow conditions had no
      apparent effect on the type, location, or severity of injury and the reported use
      of alcohol and drugs was low (7%). It was estimated that snowboarders comprised
      20 to 25% of participants on the slope but represented 45% of emergency
      department visits. CONCLUSIONS: There exists a wide spectrum of injuries from
      snowboarding, ranging from common extremity injuries to potentially life
      threatening nonorthopedic trauma.

PMID- 8760545
TI  - Analysis of quality of life in polytraumatized patients two years after discharge
      from an intensive care unit.
AB  - OBJECTIVE: Analysis of quality of life of polytraumatized critical care patients.
      DESIGN: Prospective study. MATERIAL AND METHODS: Patients admitted in a 2-year
      period in a traumatologic intensive care unit (ICU) were evaluated. A quality of
      life questionnaire was completed on admission (N = 351), 1 year and 2 years after
      discharge from the ICU. The three questionnaires evaluated patients' ability to
      function and communicate over the previous 2 months. A quality of life score of 0
      corresponded to no limitations. Quality of life was also evaluated by the Glasgow
      Outcome Scale. Information was collected on the severity of illness and the
      diagnosis prompting ICU admission. RESULTS: The mean quality of life score of
      survivors worsened from 0.46 +/- 0.11 points on ICU admission to 6.68 +/- 0.41 1
      year after discharge, and then improved to 4.86 +/- 0.38 2 years after discharge,
      although the quality of life score continued to be worse than on admission (p <
      0.001). On admission, 93.2% of patients had normal quality of life (0 points),
      after 1 year 36.5% were normal, and after 2 years 51.6% were normal. Three
      patients (0.9%) remained in vegetative state. On admission, 96.6% were working,
      while after 2 years, only 57.5% had returned to employment, although the high
      levels of unemployment in our country during this study may have been a
      particular factor in this result. All age groups except pediatric patients showed
      a worsened quality of life after 2 years, and patients over 60 years had worst
      scores on admission and after 1 and 2 years. Patients with least severity by
      Acute Physiology and Chronic Health Evaluation (APACHE) II score (< 10 points)
      had a better quality of life score after 1 and 2 years. Severity by Injury
      Severity Score showed patients with > 25 points having the greatest deterioration
      in quality of life. A multivariate study showed that quality of life after 2
      years is influenced by age, severity of injury, and previous quality of life.
      CONCLUSIONS: Polytraumatized patients admitted into ICU showed a worsening of
      their quality of life 1 and 2 years after ICU discharge, with an improvement
      between 1 and 2 years. Quality of life after 2 years is influenced by age,
      severity of illness, and previous quality of life.

PMID- 8760546
TI  - Hyperbaric oxygen therapy in the management of crush injuries: a randomized
      double-blind placebo-controlled clinical trial.
AB  - Hyperbaric Oxygen (HBO) therapy is advocated for the treatment of severe trauma
      of the limbs in association with surgery because of its effects on peripheral
      oxygen transport, muscular ischemic necrosis, compartment syndrome, and infection
      prevention. However, no controlled human trial had been performed until now to
      specify the role of HBO in the management of crush injuries. Thirty-six patients
      with crush injuries were assigned in a blinded randomized fashion, within 24
      hours after surgery, to treatment with HBO (session of 100% O2 at 2.5 atmosphere
      absolute (ata) for 90 minutes, twice daily, over 6 days) or placebo (session of
      21% O2 at 1.1 ata for 90 minutes, twice daily, over 6 days). All the patients
      received the same standard therapies (anticoagulant, antibiotics, wound
      dressings). Transcutaneous oxygen pressure (PtCO2) measurements were done before
      (patient breathing normal air) and during treatment (HBO or placebo) at the
      first, fourth, eighth, and twelfth sessions. The two groups (HBO group, n = 18;
      placebo group, n = 18) were similar in terms of age; risk factors; number, type
      or location of vascular injuries, neurologic injuries, or fractures; and type,
      location, or timing of surgical procedures. Complete healing was obtained for 17
      patients in the HBO group vs. 10 patients in the placebo group (p < 0.01). New
      surgical procedures (such as skin flaps and grafts, vascular surgery, or even
      amputation) were performed on one patient in the HBO group vs. six patients in
      the placebo group (p < 0.05). Analysis of groups of patients matched for age and
      severity of injury showed that in the subgroup of patients older than 40 with
      grade III soft-tissue injury, wound healing was obtained for seven patients
      (87.5%) in the HBO group vs. three patients (30%) in the placebo group (p <
      0.05). No significant differences were found in the length of hospital stay and
      number of wound dressings between groups. For the patients with complete healing,
      the PtCO2 values of the traumatized limb, measured in normal air, rose
      significantly between the first and the twelfth sessions (p < 0.001). No
      significant change in PtCO2 value was found for the patients whose healing
      failed. The Bilateral Perfusion Index (BPI = PtCO2 of the injured limb/PtCO2 of
      the uninjured limb) at the first session increased significantly from 1 ata air
      to 2.5 ata O2 (p < 0.05). In patients with complete healing, the BPI was
      constantly greater than 0.9 to 2.5 ata O2 during the following sessions, whereas
      the BPI in air progressively rose between the first and the twelfth sessions (p <
      0.05), reaching normal values at the end of the treatment. In conclusion, this
      study shows the effectiveness of HBO in improving wound healing and reducing
      repetitive surgery. We believe that HBO is a useful adjunct in the management of
      severe (grade III) crush injuries of the limbs in patients more than 40 years
      old.

PMID- 8760547
TI  - Pseudoaneurysm of the descending genicular artery after arthroscopic
      meniscectomy: report of a case.
AB  - Vascular injuries in the arthroscopic meniscectomy of the knee are uncommon. A
      case of pseudoaneurysm of the descending genicular artery in a 39-year-old man,
      after medial arthroscopic meniscectomy, is reported. The pseudoaneurysm was
      simple to diagnose with computed tomographic scan and angiography, and treatment
      was successful surgical resection.

PMID- 8760548
TI  - Central acetabular fracture-dislocation following electroconvulsive therapy:
      report of two similar cases.
AB  - Acetabular fracture-dislocations usually occur as a result of high velocity
      trauma. Such fractures following electroconvulsive therapy are extremely rare. In
      this report, two similar cases of acetabular fractures and central fracture
      dislocations following ECT are presented. This rare complication could be
      eliminated easily by using short-acting anaesthetic agents and muscle relaxants.

PMID- 8760549
TI  - Ventricular fibrillation in the patient with blunt trauma: not always
      exsanguination.
AB  - Three cases of successful prehospital resuscitation of blunt trauma patients
      sustaining cardiac arrest resulting from ventricular fibrillation are reported.
      Although probably uncommon, ventricular fibrillation not caused by severe
      hypovolemia, exsanguination, or severe hypoxia in the setting of blunt trauma
      might be a treatable cause of cardiac arrest. Early electrocardiographic
      monitoring of patients with blunt trauma, including those with cardiac arrest,
      can detect this small, yet easily salvageable group of patients.

PMID- 8760550
TI  - Traumatic rupture of a wandering spleen in a child: case report and literature
      review.
AB  - A case of traumatic rupture of a wandering spleen in a 5-year-old girl is
      presented. To our knowledge, this is the first reported case of such injury in a
      child. The splenic injury was managed nonoperatively. The etiology and management
      of wandering spleen is discussed.

PMID- 8760551
TI  - Superolateral dislocation of an intact mandibular condyle into the temporal
      fossa: a case report.
AB  - An unusual case of superolateral dislocation of an intact mandibular condyle into
      the temporal fossa is reported. The different methods of treatment and the
      difficulties that may arise in the treatment of such cases are discussed briefly,
      and the literature is reviewed.

PMID- 8760552
TI  - Laparoscopic repair of a traumatic ventral hernia.

PMID- 8760553
TI  - Iron and infection: new developments and their implications.
AB  - Unsaturated transferrin in plasma ensures that the amount of free ferric iron
      available to bacteria is about 10(-18) mol/L. This low iron environment is
      essential for the bacteriostatic and bactericidal systems in blood, lymph, and
      exudates. Antibacterial systems are abolished when iron becomes freely available.
      This results in rapid extracellular bacterial growth and greatly increased
      bacterial virulence. In human plasma, a fall in Eh (oxidation-reduction
      potential) or pH results in the abolition or marked reduction of its bactericidal
      properties. This is highly relevant to infection after trauma, where a fall in Eh
      and pH frequently accompanies tissue damage. Bacterial resistance to antibiotics
      has put the treatment of serious infections in jeopardy. Reinforcement of natural
      means of resistance needs to be explored, as well as examining new antibacterials
      that interfere with bacterial iron metabolism.

PMID- 8760554
TI  - Looking beyond acute management.

PMID- 8760555
TI  - Reconstruction of compound tibial and soft tissue loss using a traction
      histogenesis technique.

PMID- 8760556
TI  - A case of rhabdomyolysis and subsequent renal insufficiency after spinal cord
      injury.

PMID- 8760557
TI  - Effective treatment of the multiply injured trauma patient.

PMID- 8760558
TI  - Nonoperatively managed hepatic injuries.

PMID- 8760559
TI  - Effects of UV on HIV and other infections. Introduction.

PMID- 8760560
TI  - Is phototherapy safe for HIV-infected individuals?
AB  - Patients infected with human immunodeficiency virus (HIV) have a high prevalence
      of UV radiation-responsive skin diseases including psoriasis, pruritus,
      eosinophilic folliculitis and eczemas. On the other hand, UV has been shown to
      suppress T cell-mediated immune responses and to induce activation and
      replication of HIV. These developments have prompted clinicians and investigators
      to question whether phototherapy is safe for HIV-infected individuals. We have
      reviewed these issues and hereby provide a summary and critique of relevant
      laboratory and clinical evidence.

PMID- 8760561
TI  - Effect of low-dose gamma radiation of HIV replication in human peripheral blood
      mononuclear cells.
AB  - Recent studies have demonstrated that UV light and x-irradiation enhance human
      immunodeficiency virus (HIV) gene expression. There are few published data on
      related effects of gamma-radiation. This may be of clinical relevance, as
      radiotherapy has been used extensively for the treatment of acquired
      immunodeficiency syndrome associated conditions. With this in mind, we have
      studied the effects of gamma-radiation on HIV replication in mononuclear cells
      (MC). These cells were obtained from five seronegative healthy donors, exposed to
      0-200 cGy gamma-radiation, stimulated with phytohemagglutinin-P (PHA-P) for 24 h,
      infected with a laboratory strain of HIV (HTLV-IIIB, multiplicity of infection =
      0.001), then carried in culture for 14 days. Overall, when considering p24
      antigen levels on days 7 and 11 in cultures established from cells exposed to 50
      cGy, the maximal levels were significantly higher than those measured in the
      parallel control cultures taken as a whole (P < 0.05), with viral replication
      enhanced as much as 1000-fold in one case. No significant cytotoxicity was
      observed following exposure to doses up to 50 cGy. The mechanism of the observed
      effect remains unknown but may relate to direct gene activation and/or free
      radical generation, leading to such activation. To date, there is no evidence
      that viral stimulation occurs following therapeutic radiation in a clinical
      setting.

PMID- 8760562
TI  - UV radiation and mouse models of herpes simplex virus infection.
AB  - Orolabial human infections with herpes simplex virus type 1 (HSV-1) are very
      common; following the primary epidermal infection, the virus is retained in a
      latent form in the trigeminal ganglia from where it can reactivate and cause a
      recrudescent lesion. Recrudescences are triggered by various stimuli including
      exposure to sunlight. In this review three categories of mouse models are used to
      examine the effects of UV irradiation on HSV infections: these are UV exposure
      prior to primary infection, UV exposure as a triggering event for recrudescence
      and UV exposure prior to challenge with virus in mice already immunized to HSV.
      In each of these models immunosuppression occurs, which is manifest, in some
      instances, in increased morbidity or an increased rate of recrudescence. Where
      known, the immunological mechanisms involved in the models are summarized and
      their relevance to human infections considered.

PMID- 8760563
TI  - Medical UV exposures and HIV activation.
AB  - This paper presents the first attempt to evaluate the potential of clinical UV
      exposures to induce the human immunodeficiency (HIV) promoter and, thus, to
      upregulate HIV growth in those skin cells that are directly affected by the
      exposure. Using the data for HIV promoter activation in vitro, we computed UVB
      and psoralen plus UVA (PUVA) doses that produce 50% of the maximal promoter
      activation (AD50). Then, using (a) literature data for UV transmittance in the
      human skin, (b) a composite action spectrum for HIV promoter and pyrimidine dimer
      induction by UVB and (c) an action spectrum for DNA synthesis inhibition by PUVA,
      we estimated the distribution of medical UVB and PUVA doses in the skin. This
      allowed us to estimate how deep into the skin the HIV-activating doses might
      penetrate in an initial and an advanced stage of UVB or PUVA therapy. Such
      analysis was done for normal type II skin and for single exposures. The results
      allow us to predict where in the skin the HIV promoter may be induced by selected
      small and large therapeutic UVB or PUVA doses. To accommodate changes in skin
      topography due to disease and UV therapy, our considerations would require
      further refinements. For UVB we found that, when the incident dose on the surface
      of the skin is 500 J/m2 (290-320 nm) (initial stage of the therapy), the dose
      producing 50% of the maximal HIV promoter activation (ADUVB50) is limited to the
      stratum corneum. However, with an incident dose of 5000 J/m2 (an advanced stage
      of the therapy), ADUVB50) may be delivered as far as the living cells of the
      epidermis and even to some parts of the upper dermis. For PUVA we found that,
      when the incident UVA doses are 25 or 100 kJ/m2 (320-400 nm) (an initial and an
      advanced stage of therapy, respectively), and the 8-methoxypsoralen concentration
      in the blood is 0.1 microgram/mL (the desired level), the combined doses to the
      mid epidermis (and some areas of the upper dermis) are well below the 50% HIV
      promoter-activating PUVA dose (ADPUVA50). Only under the worst scenario
      conditions, i.e. an exceptionally high drug concentration in the patient's
      tissues and localization of HIV in the nearest proximity to the skin surface,
      would the combined PUVA dose expected during photochemotherapy exceed ADPUVA50.
      These results suggest that the probability of HIV activation in the epidermis by
      direct mechanisms is higher for UVB than for PUVA treatment. However,
      complexities of the UV-inducible HIV activation and immunomodulatory phenomena
      are such that our results by themselves should not be taken as an indication that
      UVB therapy carries a higher risk than PUVA therapy when administered to HIV
      infected patients.

PMID- 8760564
TI  - Does exposure to UV radiation induce a shift to a Th-2-like immune reaction?
AB  - In addition to being the primary cause of skin cancer, UV radiation is immune
      suppressive and there appears to be a link between the ability of UV to suppress
      the immune response and induce skin cancer. Cytokines made by UV-irradiated
      keratinocytes play an essential role in activating immune suppression. In
      particular, we have found that keratinocyte-derived interleukin (IL)-10 is
      responsible for the systemic impairment of antigen-presenting cell function and
      the UV-induced suppression of delayed-type hypersensitivity (DTH). Antigen
      presentation by splenic adherent cells isolated from UV-irradiated mice to T
      helper-1 type T (Th1) cells is suppressed, whereas antigen presentation to T
      helper-2 type T (Th2) cells is enhanced. The enhanced antigen presentation to Th2
      cells and the impaired presentation to Th1 cells can be reversed in vivo by
      injecting the UV-irradiated mice with monoclonal anti-IL-10 antibody.
      Furthermore, immune suppression can be transferred from UV-irradiated mice to
      normal recipients by adoptive transfer of T cells. Injecting the recipient mice
      with anti-IL-4 or anti-IL-10 prevents the transfer of immune suppression,
      suggesting the suppressor cells are Th2 cells. In addition, injecting UV
      irradiated mice with IL-12, a cytokine that has been shown to be the primary
      inducer of Th1 cells, and one that prevents the differentiation of Th2 cells in
      vivo, reverses UV-induced immune suppression. These findings support the
      hypothesis that UV exposure activates IL-10 secretion, which depresses the
      function of Th1 cells, while enhancing the activity of Th2 cells.

PMID- 8760565
TI  - Mechanism of UVB-induced suppression of the immune response to Mycobacterium
      bovis bacillus Calmette-Guerin: role of cytokines on macrophage function.
AB  - Previously we demonstrated that treatment of mice with either UVB radiation or
      supernatants derived from UVB-irradiated PAM 212 keratinocytes decreased the
      induction of the delayed-type hypersensitivity (DTH) response to Mycobacterium
      bovis bacillus Calmette-Guerin (BCG), impaired the clearance of bacteria from
      their lymphoid organs and also altered macrophage functions. In order to
      characterize the cytokines involved in these phenomena, UV-irradiated mice were
      injected with antibodies to interleukin-10 (IL-10), transforming growth factor
      beta 1 (TGF-beta 1), or tumor necrosis factor-alpha (TNF-alpha). Injection of UVB
      irradiated mice with anti-IL-10 immediately after UV irradiation restored the DTH
      response and reversed the UV-induced inhibition of bacterial clearance. Injection
      of UV-irradiated mice with anti-TGF-beta only partially restored the DTH response
      although it allowed a better clearance of BCG than injection of mice with the
      control antibody. In contrast, injection of anti-TNF-alpha did not affect the UVB
      induced suppression of DTH or impaired bacterial clearance. Similarly, the
      ability of macrophages to phagocytose BCG and kill the intracellular organisms
      was restored to almost normal levels after injecting UV-irradiated mice with
      antibodies specific for IL-10 or TGF-beta. Injection of mice with either
      recombinant IL-10 or TGF-beta mimicked the effect of whole-body UV irradiation on
      immune function. These results suggest that IL-10 has a major role in UV-induced
      suppression of both DTH to BCG and impairment in the clearance of bacteria and
      that TGF-beta has a more significant role in blocking bacterial clearance.
      Furthermore, these cytokines seem to modulate immune responses by altering
      macrophage functions in UVB-irradiated mice.

PMID- 8760566
TI  - PUVA therapy is preferable to UVB phototherapy in the management of HIV
      associated dermatoses.
AB  - Both methoxsalen plus UVA (PUVA) therapy and UVB phototherapy are commonly used
      in the management of human immunodeficiency virus-associated dermatoses but UVB
      phototherapy appears to be the preferred treatment. There are several
      considerations, in particular therapeutic efficacy and therapeutic profile, which
      suggest that PUVA therapy might be more effective. This needs to be established
      in clinical trials.

PMID- 8760567
TI  - Risk assessment of UVB effects on resistance to infectious diseases.
AB  - The aim of this study was to develop a quantitative risk assessment of lowered
      resistance to infections in humans due to (solar) ultraviolet B (UVB) exposure.
      We followed the steps for risk assessment as defined by the U.S. National Academy
      of Sciences: (1) hazard identification, (2) dose-response assessment, (3)
      exposure assessment, and (4) risk characterization. For step 1, the suppressory
      effects of UVB radiation on the immune system have been reviewed, supplemented
      with new data, and analyzed. Experiments on UV-induced immunosuppression cannot
      be performed with humans for ethical reasons, but herpes simplex virus infection
      appears to be the human paradigm. Thus, UVB radiation appears to be a potential
      hazard to immunologic functions. Step 2 is crucial, but dose-response
      relationships for infections have never been measured in humans. We used our
      earlier dose-response rat data for suppression of lymphocyte stimulation and
      computed that the UVB dose resulting in a 50% reduction of lymphocyte stimulation
      by Listeria monocytogenes is 6.800 J/m2. Using mixed skin lymphocyte response
      assays we found that humans are 3.8 times less sensitive than rats (interspecies
      variation [IEV]). To account for the 2.5 percentile of most susceptible
      individuals in a population, an additional factor (intraspecies variation [IAV])
      was introduced (0.5 for humans). Using these data, we computed that 13.100 J/m2
      of UVB radiation emitted by FS40 lamps would suppress 50% of the proliferative
      response of lymphocytes to L. monocytogenes in most sensitive skin type 2 humans.
      In step 3, we assumed the action spectrum for the responses analyzed by us as
      identical to an action spectrum for suppression of contact hypersensitivity that
      is available in the literature. This led us to step 4, where we calculated that
      approximately 100 min of solar exposure at around noon in Italy or Spain would
      suppress the resistance to infections by L. monocytogenes in the most sensitive
      humans.

PMID- 8760568
TI  - The skin immune system in the course of HIV-1 infection.
AB  - In human immunodeficiency virus-1 (HIV-1) infection, diseases of the skin and
      mucous membranes frequently dominate the clinical picture as a consequence of
      progressive immunodeficiency. Functional impairment of the skin immune system,
      manifesting as a loss of the skin delayed-type hypersensitivity response is very
      likely due to the infection of immunocompetent cells of the skin by HIV-1.
      Besides CD4+ T cells, antigen-presenting Langerhans cells have been established
      as major targets of HIV-1 infection. The close physical contact of Langerhans
      with T lymphocytes during immune activation suggests central role of these cells
      in the dissemination of HIV-1 and the subsequent breakdown of the skin immune
      system. In addition, there are indications that mucosal Langerhans cells may
      represent preferred target cells for certain HIV-1 subtypes and thereby
      facilitate mucocutaneous transmission of HIV-1.

PMID- 8760569
TI  - Signal transduction and HIV transcriptional activation after exposure to
      ultraviolet light and other DNA-damaging agents.
AB  - Short wavelength (254 nm) ultraviolet light (UVC) radiation was much more potent
      in activating transcription of human immunodeficiency virus 1 (HIV) reporter
      genes stably integrated into the genomes of human and monkey cells than ionizing
      radiation (IR) from a 137Cs source at similarly cytotoxic doses. A similar
      differential was also observed when c-jun transcription levels were examined.
      However, these transcription levels do not correlate with activation of nuclear
      factor (NF)-kappa B and AP-1 measured by band-shift assays, i.e. both types of
      radiation produce similar increases in NF-kappa B and AP-1 activity, suggesting
      existence of additional levels of regulation during these responses. Because of
      the well-established involvement of cytoplasmic signaling pathways in the
      cellular response to tumor necrosis factor-alpha (TNF-alpha), UVC, and IR using
      other types of assays, the role of TNF-alpha in the UVC response of HIV and c-jun
      was investigated in our cell system. We demonstrate that UVC and TNF-alpha
      activate HIV gene expression in a synergistic fashion, suggesting that it is
      unlikely that TNF-alpha is involved in UVC activation of HIV transcription in
      stably transfected HeLa cells. Moreover, maximum TNF-alpha stimulation resulted
      in one order of magnitude lower levels of HIV expression than that observed after
      UVC exposure. We also observed an additive effect of UVC and TNF-alpha on c-jun
      steady-state mRNA levels, suggestive of a partial overlap in activation mechanism
      of c-jun by UVC and TNF-alpha; yet these responses are distinct to some extent.
      Our results indicate that the HIV, and to some extent also the c-jun,
      transcriptional responses to UVC are not the result of TNF-alpha stimulation and
      subsequent downstream cytoplasmic signaling events in HeLa cells. Additional
      levels of regulation that do not directly involve the NF-kappa B and AP-1
      transcription factors, such as changes in chromatin structure associated with the
      UV repair process, may also be important for a full transcriptional response of
      HIV and c-jun to UVC. In addition to the new data, this report also summarizes
      our current views regarding UVC-induced activations of HIV gene expression in
      stably transfected cells.

PMID- 8760570
TI  - The origin of magnetic field dependent recombination in alkylcobalamin radical
      pairs.
AB  - Magnetic field effect studies of alkylcobalamin photolysis provide evidence for
      the formation of a reactive radical pair that is born in the singlet spin state.
      The radical pair recombination process that is responsible for the magnetic field
      dependence of the continuous-wave (CW) quantum yield is limited to the diffusive
      radical pair. Although the geminate radical pair of adenosylcob(III)alamin also
      undergoes magnetic field dependent recombination (A.M. Chagovetz and C. B.
      Grissom, J. Am. Chem. soc. 115, 12152-12157, 1993), this process does not account
      for the magnetic field dependence of the CW quantum yield that is only observed
      in viscous solvents. Glycerol and ethylene glycol increase the microviscosity of
      the solution and thereby increase the lifetime of the spin-correlated diffusive
      radical pair. This enables magnetic field dependent recombination among spin
      correlated diffusive radical pairs in the solvent cage. Magnetic field dependent
      recombination is not observed in the presence of nonviscosigenic alcohols such as
      isopropanol, thereby indicating the importance of the increased microviscosity of
      the medium. Paramagnetic radical scavengers that trap alkyl radicals that escape
      the solvent cage do not diminish the magnetic field effect on the CW quantum
      yield, thereby ruling out radical pair recombination among randomly diffusing
      radical pairs, as well as excluding the involvement of solvent-derived radicals.
      Magnetic field dependent recombination among alkylcobalamin radical pairs has
      been simulated by a semi-classical model of radical pair dynamics and
      recombination. These calculations support the existence of a singlet radical pair
      precursor.

PMID- 8760571
TI  - Evaluation of an economical sunlamp that emits a near solar UV power spectrum for
      conducting photoimmunological and sunscreen immune protection studies.
AB  - Expense and inconvenience have restricted the use of the filtered xenon are lamp
      (solar simulator) as a UV source for conducting large-scale animal studies.
      Because sunscreen immunoprotective levels are significantly affected by the UV
      power spectrum of the source it is imperative that a solar simulating source be
      used for accurate measurements of sunscreen protection levels that are relevant
      to human LV exposures from sunlight. However, relatively inexpensive sunlamps,
      e.g. the UVA-340, that emit a UV power spectrum similar to that of a solar
      simulator are available. Unlike FS-type UVB sunlamps, which have a significant
      amount of effective immunosuppressive non-solar UV energy at wavelengths below
      295 nm, the immunosuppression effectiveness spectrum of UVA-340 sunlamps was
      nearly identical to that of a solar simulator. The purpose of this study was to
      evaluate this sunlamp for conducting photoimmunological and sunscreen immune
      protection studies. Groups of C3H mice were exposed to a range of UVA-340 sunlamp
      doses (0.25 kJ/m2 to 20.0 kJ/m2) to establish a dose-response curve and determine
      the minimum immune suppression dose (MISD) for iduction of local-type suppression
      of contact hypersensitivity (CH). The MISD, defined as the lowest UV dose given
      to produce approximately 50% suppression of the CH response in mice, was
      determined to be 1.0 kJ/m2 for UVA-340 sunlamps. Immune protection tests on four
      marketed sunscreen lotions (sun protection factors [SPF] 4, 8, 15 and 30) were
      then conducted with UVA-340 sunlamps using MISD as the endpoint. The immune
      protection factors for these sunscreens were equivalent to the level of
      protection predicted by their labeled SPF. These results are similar to those we
      have previously obtained using a solar simulator. We conclude from these data
      that the immunosuppressive effects of UVA-340 sunlamps are similar to those of a
      solar simulator; however, further studies are needed to determine if UVA-340, or
      similar, sunlamps are a viable alternative to the solar simulator for conducting
      large-scale animal experiments that require a relevant UV solar spectrum.

PMID- 8760572
TI  - Quantitative determination of cyclobutane thymine dimers in DNA by stable isotope
      dilution mass spectrometry.
AB  - In order to understand the role of UV-induced DNA lesions in biological processes
      such as mutagenesis and carcinogenesis, it is essential to detect and quantify
      DNA damage in cells. In this paper we present a novel and both highly selective
      and sensitive assay using capillary gas chromatography (GC) combined with mass
      spectrometry (MS) for the detection and accurate quantitation of a major product
      of UV-induced DNA damage (cis-syn cyclobutadithymine). Quantitation of the
      cyclobutane thymine dimer was achieved by the use of an internal standard in the
      form of a stable 2H-labeled analogue. Both isotopically labeled and nonlabeled
      dimers were prepared directly from their corresponding monomers. Each was
      identified as their trimethylsilyl ether derivative by GC-MS. Calibration plots
      were obtained for known quantities of both nonlabeled analyte and internal
      standard. Quantitation of cis-syn cyclobutadithymine was demonstrated in DNA
      exposed to UVC radiation over a dose range of 0 to 3500 J m-2. Under the
      conditions used, the limit of detection was found to be 20-50 fmol on column
      (equivalent to 0.02-0.05 nmol dimer per mg DNA). The results of the present study
      indicate that capillary GC-MS is an ideally suited technique for selective and
      sensitive quantification of cis-syn cyclobutadithymine in DNA and hence UV
      induced DNA damage.

PMID- 8760573
TI  - Lethal effect induced in Pseudomonas aeruginosa Exposed to Ultraviolet-A
      radiation.
AB  - Ultraviolet-A (365 nm, 120 kJ/m2/h) exposure caused cell death in Pseudomonas
      aeruginosa at doses at which Escherichia coli cell viability was not affected. We
      have not found that UVA induced growth delay or any other sublethal effect.
      Irradiated suspensions of P. aeruginosa showed a marked reduction in membrane
      bound succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH) activities.
      Succinate-driven respiration and several nutrient transport systems were also
      inhibited. Whereas SDH and LDH activities were independent of the irradiation
      conditions, cell viability, respiration and transport systems were protected when
      irradiation was performed in an N2 atmosphere. A similar protective effect was
      observed when cells were grown in media containing glycerol or when
      preirradiation bacterial growth was carried out at 30 degrees C (instead of 37
      degrees C). Results suggest that UVA induces a differential damaging effect on
      several biochemical functions of P. aeruginosa. The UVA- induced photodamage may
      fall into two categories: indirect damage mediated by oxygen (cell killing and
      inhibition of respiration and transport systems) and direct damage to SDH and LDH
      (apparently not oxygen dependent). These enzymes and leucine transport appear not
      to be involved in the lethal effect described herein because they were altered
      despite viability-preserving conditions

PMID- 8760574
TI  - Effect of the UV modification of alpha-crystallin on its ability to suppress
      nonspecific aggregation.
AB  - Recent studies have shown that structural modifications of alpha-crystallin
      during lens aging decrease it's effectiveness as a molecular chaperone. Some of
      these posttranslational modifications have been linked to UV radiation, and this
      study was undertaken to investigate the effect of UV irradiation on the ability
      of alpha-crystallin to suppress nonspecific aggregation. The effect of 3
      hydroxykynurenine (3-HK) was also investigated as a model for its glucoside (3
      HKG), a main lens chromophore that has been linked to photochemical changes in
      the human lens. Alpha- and gamma-crystallin solutions (1 mg/mL, 1:0.125 wt/wt)
      were photolyzed (transmission above 295 nm) for various time intervals. Thermal
      denaturation of gamma-crystallin with or without alpha-crystallin was carried out
      at 70 degrees C and increases in light scattering were measured at 360b nm. We
      found that (1) irradiation of gamma-crystallin increased its susceptibility to
      heat-induced scattering. The addition of alpha-crystallin protects it against
      thermal denaturation, although its ability to do so decreases the longer gamma
      crystallin is irradiated and (2) irradiation of alpha-crystallin decreases its
      ability to suppress nonspecific aggregating and the presence of of 3-HK during
      irradiation decreases it further. Our results indicate that posttranslational
      modifications of alpha-crystallin due to UV irradiation affect the sites and
      mechanisms by which it interacts with gamma-crystallin. The kinetics of gamma
      crystallin unfolding during thermal denaturation were also analyzed. We found
      that a simple two state model applies for nonirradiated gamma-crystallin. This
      model does not hold when gamma-crystallin is irradiated in the presence or
      absence of alpha-crystallin. In these cases, two step or multistep mechanisms are
      more likely.

PMID- 8760575
TI  - Formation of cyclobutane thymine dimers from UVA photosensitization of
      pyridopsoralen monoadducted DNA.
AB  - The present report provides evidence that thymine dimerization can be UVA
      photosensitized at a tetranucleotide, 5'-TATT-3', by a 7-methyl-pyrido(3,4
      c)psoralen monoadduct in DNA. The efficiency of the photoprocess depends on the
      tetranucleotide flanking sequences. These results demonstrate that one DNA lesion
      can originate the contiguous formation of a second type of lesion and emphasize
      the sequence-specific response to interaction of drugs with DNA. Results are
      related to the sensitivity of DNA to 1,10-phenanthroline-cuprous ion complex
      nucleolytic activity and discussed in terms of the major role of local
      deformability of DNA in interaction with ligands.

PMID- 8760576
TI  - 8-methoxypsoralen and ultraviolet a radiation activate the human elastin promoter
      in transgenic mice: in vivo and in vitro evidence for gene induction.
AB  - Treatment of skin diseases with the combination of 8-methoxypsoralen and
      ultraviolet A radiation (PUVA) results in clinical alterations in treated skin
      that resemble those observed in chronically photodamaged skin. The PUVA-treated
      patients develop nonmelanoma skin cancers, pigmentary alterations and wrinkling
      characteristic of sun-induced changes. The major alteration in the dermis of sun
      damaged skin is the deposition of abnormal elastic fibers, termed solar
      elastosis. Up-regulation of elastin promoter activity in dermal fibroblasts
      explains the excess elastic tissue but not the reason for the aberrant morphology
      of the elastotic material. In order to study photoaging in an experimental
      system, we utilized a transgenic mouse line that expresses the human elastin
      promoter/chloramphenicol acetyltransferase construct in a tissue-specific and
      developmentally regulated manner. Although UVB radiation has been demonstrated to
      increase promoter activity in vitro, UVA fails to demonstrate a similar effect at
      the doses utilized. In this study, we demonstrate the ability of PUVA treatment
      to up-regulate elastin promoter activity both in vitro and in vivo. These data
      help to explain the development of photoaging in sun-protected PUVA-treated skin.
      We attribute the up-regulation of elastin promoter activity in response to PUVA
      to the formation of DNA photoadducts, which do not occur in response to UVA
      radiation alone.

PMID- 8760577
TI  - Photodynamic effects of hypericin on lipid peroxidation and antioxidant status in
      melanoma cells.
AB  - Photodynamic-induced cytotoxicity by hypericin (HYP) was studied on three human
      melanoma cell lines: one pigmented cell line (G361) and two amelanotic cell lines
      (M18 and M6). No significant variation in the rate of uptake and in the maximum
      level of HYP incorporation for the different cells was observed. In the dark, no
      cytotoxicity was observed in the range 0-10-6 M HYP for the three cell lines.
      Amelanotic cells were found to be more sensitive than pigmented cells to
      irradiation of HYP with visible light (lambda > 590 nm). In addition, for the
      three cell lines HYP-induced photocytotoxicity was found to be drug-dose and
      light-dose dependent. Under the conditions used, thiobarbituric acid-reacting
      substances (TBARs) were significantly increased in amelanotic cells after
      irradiation (P < 0.0001). By contrast, the amount of TBARS remained unchanged in
      pigmented cells. Antioxidant defenses including enzymes and glutathione (GSH)
      were assayed before and after HYP photosensitization. Significantly increased
      total SOD activity was observed after photosensitizaton for amelanotic cells (P <
      0.05), while glutathione peroxidase (GSHPx) and catalase (Cat) activities but
      also GSH levels were significantly decreased (P < 0.01). In pigmented cells a
      significantly increased Cat activity was found (P < 0.05), whereas GSHPx was
      unaffected after irradiation. It can be inferred that (a) HYP may be an effective
      PDT agent for melanoma and (b) there is a relationship between melanin content
      and sensitivity to HYP phototoxicity in human melanoma cells.

PMID- 8760578
TI  - Spectroscopic and biological testing of photobleaching of porphyrins in
      solutions.
AB  - The photobleaching of protoporhyrin IX (PP IX) and hematoporphyrin derivative
      (HpD) solutions was followed using three different methods: spectrophotometry,
      fluorometry and photodynamically induced cytotoxicity. The latter entails
      photoirradiation of HT29 human colon adenocarcinoma cells in the presence of
      preirradiated solutions of HpD and PP IX (lambda < or = 415 nm). The highest
      cytotoxicity was observed in the presence of unirradiated dye and decreased with
      the time of preirradiation. This decay in photocytotoxicity was further used to
      determine the porphyrin photobleaching kinetics in solution. For both
      sensitizers, quantum yields of photobleaching obtained by matching fluorescence
      were higher than that obtained from absorbance measurements (10 and 11 times for
      HpD and PP IX, respectively). This difference reflects preferential
      photobleaching of photolabile monomeric forms compared to aggregated. The highest
      quantum yield was obtained in the biological test (decay in cytotoxicity) which
      was 14 times higher for HpD and 30 times higher for PP IX than the quantum yield
      obtained from absorbance measurements. The absence of correlation between
      biological and fluorescence measurements has to be taken into account in the in
      vivo situation. Dark storage of preirradiated sensitizers (37 degrees C, 24 h)
      completely restored photocytotoxity for PP IX but only partially for HpD, whereas
      fluorescence patterns were partially restored for both sensitizers.

PMID- 8760579
TI  - Indications for the occurrence of nitric oxide synthases in fungi and plants and
      the involvement in photoconidiation of Neurospora crassa.
AB  - Indications for the occurrence of nitric oxide synthases in Dictyostelium,
      Neurospora, Phycomyces and the leguminous plant Mucuna hassjoo as well as a
      physiological role of nitric oxide in Neurospora crassa are demonstrated. An
      exogenous nitic oxide donor, sodium nitroprusside, inhibited light-stimulated
      conidiation in N. crassa. Specific inhibitors of nitric oxide synthase, like the
      arginine derivatives NG -nitro-L-arginine (L-NA) and NG-nitro-L-arginine-methyl
      ester (L-NAME), enhanced conidiation in darkness nad in the light, whereas the
      stereoisomer D-NAME was inactive. This communication reports to our knowledge the
      first time the presence of enzymatic activity of nitric oxide synthase in fungi
      and a higher plant and an effect of nitric oxide in fungal photo-physiology.

PMID- 8760580
TI  - Lactation and the risk of breast cancer in an Italian population.
AB  - The relation between breast feeding and breast cancer was investigated in a
      multicentric case-control study conducted in Italy on 2,167 parous women with
      histologically confirmed breast cancer, diagnosed within 1 year, and 2,208 parous
      control women admitted to hospitals in the same catchment areas of cases for
      acute, non-neoplastic, non-gynecological non-hormone-related diseases. Compared
      with women who had never tried to lactate, those who had always failed had a
      multivariate odds ratio (OR; adjusted for parity, education and several other
      potential confounding factors) of 0.94, and those who had lactated had an OR of
      1.17. The multivariate ORs of women who had breast fed 1, 2 and 3 or more
      children were, respectively, 1.14, 1.18 and 1.32, compared with women who had
      never lactated. None of these ORs was statistically significant. Compared with
      women who had never breast fed, the multivariate ORs were 1.19 for women
      reporting less than 6 months of breast feeding, 1.15 for 6-11 months, 1.34 for 12
      17 months, 1.10 for 18-23 months and 0.86 for 24 months or more. No appreciable
      difference was evident across strata of age, menopausal status, parity and age at
      first birth, while there was a hint of interaction with education. Our study
      therefore excluded any appreciable protective role for lactation in breast cancer
      risk, with the patterns of lactation in this European population, aside from the
      protective role of parity on breast carcinogenesis.

PMID- 8760581
TI  - Risk and prognosis of cancer in middle-aged women who have experienced the death
      of a child.
AB  - First, we studied the relative risk of cancer among women born between 1935 and
      1954 who had experienced a child's death, compared with women without this
      experience. Second, we examined whether survival was any different between cancer
      patients in the 2 groups. The study was a population-based nested case-control
      study that included 14,669 cancer cases and 29,750 age-matched controls. The
      women who were included as incident cases were further analyzed using Cox
      regression in a study of total survival. The overall relative risk of cancer
      among women who had lost a child was nearly identical to that of women who had
      not lost a child (OR = 0.96, 95% confidence interval 0.87-1.07), after adjustment
      for age and parity. In the analysis of specific cancer sites, there was no
      difference in relative risk between the 2 groups. In relation to cancer survival,
      we found that patients who had lost a child had an overall risk of dying that was
      nearly identical to patients who had not had this experience (HR = 1.08, 95%
      confidence interval 0.92-1.26), after adjustment for age and stage at diagnosis.
      For specific sites of cancer, the results also showed no difference in survival
      between the 2 groups. In conclusion, risk and survival of cancer were not
      different among women who had experienced the death of a child from the risk and
      survival among women without this experience.

PMID- 8760582
TI  - Alpha-tocopherol and hydroperoxide content in breast adipose tissue from patients
      with breast tumors.
AB  - The study of the relationship between dietary intake of vitamin E and the risk of
      breast cancer has not yielded definite conclusions with respect to causality,
      possibly due to methodological issues inherent to nutritional epidemiology. To
      avoid the pitfalls of dietary recalls, alpha-tocopherol content of adipose tissue
      was used as a biochemical indicator of long-term dietary intake of vitamin E.
      alpha-tocopherol and hydroperoxides were measured in breast adipose tissue
      obtained at the time of diagnosis from 70 patients with early breast cancer.
      Thirty women with non-malignant breast tumors served as control. Lipid
      peroxidation was monitored by quantifying conjugated dienes
      spectrophotometrically and by assaying hydroperoxides with an iodometric method;
      alpha-tocopherol was measured by HPLC associated with fluorescence detection.
      Mean alpha-tocopherol value in breast adipose tissue was significantly lower in
      breast cancer patients than in control patients, whereas the hydroperoxide
      content was significantly higher in cancer patients than in controls. The alpha
      tocopherol concentration in adipose tissue was not correlated with the clinical
      status of the patients with respect to age, menopausal status or body mass index.
      We conclude from this pilot study that breast cancer is associated with a low
      content of alpha-tocopherol in breast adipose tissue, and with an altered lipid
      oxidation pattern, which might be related to a low antioxidant status.

PMID- 8760583
TI  - Infrequent alterations of the p16INK4A gene in liver cancer.
AB  - We examined the genomic status of the p16INK4A (inhibitor of cyclin-dependent
      kinase 4 A) and cyclin-dependent kinase 4 (CDK4) genes in 62 human hepatocellular
      carcinomas (HCCs), 5 cholangiocellular carcinomas and 6 cell lines derived from
      human liver cancers. Although no samples showed the homozygous deletion of the
      p16INK4A gene, we detected intragenic mutations of the p16INK4A gene in 3 HCCs
      and one HCC cell line, which led to an amino-acid substitution or a frameshift.
      In 2 HCC samples with mis-sense mutations of the p16INK4A gene, loss of
      heterozygosity on 9p22 was also detected, suggesting that the loss of function of
      p16 was induced during hepatocarcinogenesis. On the other hand, amplification or
      rearrangement of the CDK4 gene was not detected in any samples examined in this
      study. These results indicated that the mutations or deletions of the p16INK4A
      gene are not frequent, but may play a role in a sub-set of human HCC.

PMID- 8760584
TI  - Body size indices and breast cancer risk before and after menopause.
AB  - The relationship between various body size indices and breast cancer risk before
      and after menopause was elucidated by means of a case-control study conducted
      between June 1991 and April 1994 in 6 Italian centers on 2,569 patients aged
      below 75 with histologically confirmed breast cancer, and on 2,588 controls
      admitted to the hospital for a wide spectrum of acute, non-neoplastic, non
      hormone-related diseases. Weight and, more consistently, body mass index (BMI,
      kg/m2) at diagnosis were inversely related to pre-menopausal breast cancer risk
      and directly to post-menopausal risk. An 8-unit increase in BMI resulted in an
      odds ratio of 0.8 for pre-menopausal and of 1.2 (significant) for post-menopausal
      women. Risk seemed to increase gradually after menopause in the 7th (OR for an 8
      unit BMI increase, 1.3) and 8th decades (OR, 1.6) of life. Conversely, height,
      waist-to-hip ratio, bra cup size and weight (or BMI) in adolescence and in young
      adulthood did not exert a significant or consistent influence on breast cancer
      risk. The apparent relationship with BMI at middle age and weight gain between
      age 30 years and diagnosis was eliminated by allowance for BMI at diagnosis. The
      age-related pattern of the association between BMI and breast cancer risk after
      menopause may reflect a duration-risk relationship, and resembles the effect of
      post-menopausal estrogen use, which seems greater among older women.

PMID- 8760586
TI  - A risk score for predicting outcome in patients with gastric cancer, based on
      stage, sialyl-Tn immunoreactivity and ploidy--a multivariate analysis.
AB  - Twelve variables were studied for possible prognostic value in 242 patients with
      adenocarcinoma of the stomach. Eight of these had a statistically significant
      effect on survival in univariate analyses. A multivariate analysis of 196
      patients showed that the most significant differences in survival could be
      explained by 3 independent variables acting simultaneously, namely stage of
      disease, Sialyl Tn antigen (STn) expression and aneuploidy of the tumour cells.
      By adding scores for stage (1-4 points), STn expression (0-1 points) and ploidy
      (0-1 points) a risk score based on these 3 variables defined the patients into 6
      different risk groups with statistically highly significant differences in
      survival (chi 2 = 107.74, DF = 1, p < 0.0001). Application of the risk score
      improves the prediction of outcome, may help in choosing patients for different
      treatment modalities, and allows more accurate stratification in clinical trials.

PMID- 8760585
TI  - Age at any birth and breast cancer in Italy.
AB  - To provide quantitative information on the role of age at any birth for breast
      cancer risk, we analyzed data from a cooperative Italian case-control study
      conducted between 1991 and 1994 on 2,569 incident, histologically confirmed
      breast cancer cases and 2,588 controls in hospital for acute, non-neoplastic, non
      gynecological conditions. A single logistic model was fitted, including terms for
      number of births, age at each birth and at menarche, plus age and center. Age at
      first birth was the strongest reproductive determinant of subsequent breast
      cancer risk, with an estimated increase of 4.6% per year of delay of first birth.
      This was similar to the influence of age at menarche (4.7% decrease in risk per
      year of delay of menarche). Ages at subsequent births had an independent effect
      on breast carcinogenesis, with an estimated 0.7% increase in risk per year of
      delay. Multiparity showed also an independent protection on breast cancer risk,
      and a protective effect of parity > or = 3 was evident in all strata of age at
      first birth: the odds ratio was 0.81 for 3 births and 0.70 for > or = 4 births.
      However, the effect of parity was determined by the age of occurrence of various
      births.

PMID- 8760587
TI  - Diet and other risk factors for cancer of the salivary glands:a population-based
      case-control study.
AB  - A population-based case-control study of cancer of the salivary glands, involving
      interviews of 41 incident cases and 414 controls, was conducted in Shanghai.
      After adjustment for other risk factors, occupational exposure to silica dust was
      linked to a 2.5-fold increased risk of salivary-gland cancer. The risk was also
      significantly elevated among individuals who reported ever using kerosene as
      cooking fuel or having a prior history of head X-ray examinations. Dietary
      analyses revealed a significant protective effect of consumption of dark-yellow
      vegetables or liver, with about 70% reduced risk of salivary-gland cancer among
      individuals in the highest intake group of these foods. Our findings are
      consistent with previous observations on a possible role of environmental
      exposure and radiation in the etiology of salivary-gland cancer, and suggest that
      dietary factors may contribute to the development of this malignancy.

PMID- 8760588
TI  - Comparison of hypervariable regions (HVR1 and HVR2) in positive- and negative
      stranded hepatitis C virus RNA in cancerous and non-cancerous liver tissue,
      peripheral blood mononuclear cells and serum from a patient with hepatocellular
      carcinoma.
AB  - Hepatitis C virus (HCV) infection is associated with a wide spectrum of liver
      diseases including cirrhosis and hepatocellular carcinoma (HCC). Although the
      biological relation between the virus and cirrhosis or HCC is unclear, such
      variable pathogenicity may be related to the genetic heterogeneity of HCV.
      Genetic variability of HCV was assessed by determining the nucleotide sequence
      corresponding to the hypervariable regions (HVR1 and HVR2) of the putative
      envelope protein (E2/NS1) in positive- and negative-stranded HCV RNA from the
      cancerous and surrounding non-cancerous liver tissue, peripheral blood
      mononuclear cells and serum of a patient with HCC. Nineteen distinct HVR1 amino
      acid sequences (deduced from the nucleotide sequences) were obtained from the
      patient and could be classified into 5 groups on the basis of the site and time
      of detection. Some viral isolates with the same HVR1 sequence were shown to
      replicate in both cancerous and non-cancerous liver tissue, whereas others
      replicated in HCC tissue only.

PMID- 8760589
TI  - Molecular characterization of a novel cancer cell line established from human
      carcinoma in pleomorphic adenoma (CaPA-4).
AB  - A cultured cell line (CaPA-4), derived from an undifferentiated carcinoma in a
      pleomorphic adenoma of the submandibular gland, was established through
      xenografted tumors in nude mice. Geneticin treatment eliminated surrounding mouse
      fibroblasts and yielded enriched tumor cells at an early stage of cell passage.
      In vitro, the line grew in a cobblestone pattern, revealing its epithelial
      origin. Chromosomal analysis by Giemsabanding confirmed its human origin, while
      electron microscopic examination showed its squamous-cell characteristics. CaPA-4
      cells stained positive for the c-myc and Ha-ras antibodies. Molecular analysis
      showed over-expression of both c-myc and Ha-ras mRNA, with point mutation of p53
      at codon 248 and of Ha-ras at codon 61. Amplification and rearrangement of the Ha
      ras gene were observed; however, no loss of heterozygosity (LOH) of the p53 gene
      was detected by Southern blotting. This sequence of cancer-related gene
      activation may represent the malignant transformation from benign pleomorphic
      adenoma. This report describes the establishment and molecular characterization
      of this novel cell line from carcinoma in pleomorphic adenoma exhibiting squamous
      cell differentiation. This could represent a useful model for investigating the
      cause of malignant transformation from human salivary-gland mixed tumors.

PMID- 8760590
TI  - Novel metastasis model of human lung cancer in SCID mice depleted of NK cells.
AB  - Metastasis is a critical problem in the treatment of human lung cancer. Thus, a
      suitable animal model of metastasis of human lung cancer is required for in vivo
      biological and preclinical studies. In this study, we tried to establish a
      suitable model for this, using SCID mice. Neither human SCLC H69/VP cells (5 x
      10(6)) nor squamous-cell carcinoma RERF-LC-AI cells (1 x 10(6)), injected through
      a tail vein, formed metastases in untreated SCID mice. Pre-treatment of SCID mice
      with anti-asialo GM1 serum resulted in only a few metastases of H69/VP cells, but
      pre-treatment with anti-mouse IL-2 receptor beta chain Ab (TM-beta 1) resulted in
      numerous lymph-node metastases 56 days after tumor inoculation. H69/VP-M cells,
      an in vivo-selected variant line, formed significant numbers of lymph-node
      metastases even in SCID mice pre-treated with anti-asialo GM1 serum. SCID mice
      depleted of NK cells by treatment with TM-beta 1 showed different patterns of
      metastasis when inoculated intravenously with the 2 different human lung cancer
      cell lines (H69/VP and RERF-LC-AI cells): H69/VP cells formed metastases mainly
      in systemic lymph nodes and the liver, whereas RERF-LC-AI cells formed metastases
      mainly in the liver and kidneys, with only a few in lymph nodes. A
      histopathological study showed that the metastatic colonies consisted of cancer
      cells. The numbers of metastatic colonies formed by the 2 cell lines increased
      with the number of cells inoculated. TM-beta 1 treatment of SCID mice efficiently
      removed NK cells from peripheral blood for at least 6 weeks, whereas, after
      treatment of the mice with anti-asialo GM1 serum, NK cells were recovered within
      9 days. These findings suggest that NK-cell-depleted SCID mice may be useful as a
      model in biological and pre-clinical studies on metastasis of human lung cancer.

PMID- 8760591
TI  - Establishment and characterization of two cultured cell lines derived from
      malignant rhabdoid tumors of the kidney.
AB  - Malignant rhabdoid tumor of the kidney (RTK) is a rare renal sarcoma of
      childhood. Its histogenesis is unclear, and it is highly resistant to
      multimodality therapy. To elucidate the origin and the oncogenetic potential of
      RTK, we investigated the characteristics of 2 newly established RTK cell lines,
      SWT-1 and SWT-2. Both cell lines were verified to be RTK, since they did not
      exhibit contact inhibition and exhibited intermediate filaments, a specific
      marker for RTK. These cells possess the characteristics of mesenchymal cells
      based on their positive reactions with anti-vimentin and anti-laminin antibodies
      and their negative reactions with anti-keratin and anti-desmin antibodies. The
      karyotype of SWT-1 was 46,XX and that of SWT-2 was 46,XX,del(11)(pter-p13::p12
      qter). Since 11p13 is the location of the WT-1 tumor-suppressor gene, and
      del(11p13) is associated with the aniridia-Wilms'-tumor syndrome, these findings
      link RTK with Wilms' tumor. While SWT-1 was negative for the tumor markers
      examined, SWT-2 released tissue polypeptide antigen into the culture supernatant.
      No rearrangement or amplification of the myc and ras oncogenes or of the p53
      tumor-suppressor gene were detected. Wild-type RB protein and cyclin A were
      expressed in both cells. Our data suggest that these 2 cell lines may be useful
      in identifying the oncogenetic pattern of RTK.

PMID- 8760592
TI  - Sensitivity to cis-diamminedichloroplatinum in human cancer cells is related to
      expression of cyclin D1 but not c-raf-1 protein.
AB  - Although several oncogenes, including c-myc, ras and c-raf-1, have been
      implicated in cellular resistance to ionising radiation, there is less
      information relating oncogene expression to cis-diamminedichloroplatinum (CDDP)
      resistance. However, transfection of c-myc or v-H-ras and activation of protein
      kinase C (PKC), which contributes to the RAF-1, MAP kinase signal transduction
      pathway, can influence therapeutic response to CDDP. Activation of PKC increases
      CDDP sensitivity, whilst transfected c-myc or v-H-ras induce CDDP resistance. We
      have previously reported that human in vitro cell lines show different patterns
      of sensitivity to CDDP and 4 MeV X-irradiation. In these cells radiation
      sensitivity is related to high levels of expression of the C-raf-1 proto
      oncogene. We thus predicted that cells sensitive to CDDP might show a different
      relationship to c-raf-1 expression. In addition, because cyclin D1 expression can
      be upregulated by the myc or ras oncogenes, we also chose to study putative
      relationships between cyclin D1 protein levels and intrinsic cellular sensitivity
      to CDDP and gamma-irradiation. We report that in the 16 human cell lines which we
      have studied, high cyclin D1 expression is related to CDDP resistance but has no
      relationship with radiation responsiveness, whereas high c-raf-1 expression,
      although related to radiosensitivity has no relationship with CDDP
      responsiveness.

PMID- 8760593
TI  - Tumor-infiltrating lymphocytes can be activated in situ by using in vivo
      activants plus F(ab')2 bispecific antibodies.
AB  - In vitro-activated T lymphocytes can be retargeted with anti-CD3 x anti-tumor
      bispecific antibodies (BsAb) to kill tumor cells in vitro and in vivo. The
      purpose of the present study was to examine the systemic and intra-tumor effects
      of in vivo T-cell activation with BsAb, staphylococcal enterotoxin B (SEB), and
      beta-glucan in combination with BsAb as a retargeting agent. CL-62 melanoma cells
      were injected subcutaneously into C3H/ HeN mice. Mice were subsequently treated
      with BsAb alone or with SEB or beta-glucan plus BsAb. Fresh splenocytes, lymph
      node cells and tumor-infiltrating lymphocytes (TIL) were tested for their
      proliferative response using incorporation of 3H-thymidine, and for their ability
      to lyse CL-62 cells in the presence or absence of BsAb in 4-hr 51Chromium release
      assays. Toxicity of treatments was assessed in a D-galactosamine model. BsAb,
      alone or combined with beta-glucan, had essentially no effect on systemic T-cell
      cytotoxicity, and essentially no effect on systemic proliferation, unless
      exogenous IL-2 was provided. At the tumor site, BsAb alone, BsAb plus beta
      glucan, and SEB plus BsAb all significantly increased BsAb-mediated TIL
      cytotoxicity. In contrast to the TIL-limited effects of BsAb and of BsAb plus
      beta-glucan, SEB plus BsAb markedly increased both systemic and intra-tumor T
      lymphocyte activation. Toxicity correlated with measures of systemic activation,
      with limited effects from BsAb alone and from beta-glucan plus BsAb, and with
      marked lethality from SEB plus BsAb. Overall, these results suggest moderate
      intra-tumor activation of TIL, but no measurable systemic activation after in
      vivo treatment with BsAb or beta-glucan plus BsAb. SEB plus BsAb results in
      complete T-cell activation in both systemic and intra-tumor compartments, but at
      the expense of increased systemic toxicity. In conclusion, TIL can be activated
      in situ with different combinations of in vivo activants. In vivo-activated TIL
      can be retargeted with bispecific antibodies to lyse tumor cells, and may be an
      alternative to ex vivo T-cell activation and adoptive transfer therapy.

PMID- 8760594
TI  - Tumor necrosis factor alpha is a powerful apoptotic inducer in lymphoid leukemic
      cells expressing the P-170 glycoprotein.
AB  - Multidrug resistance (MDR) is a phenomenon by which tumor cells exposed to a
      single anti-proliferative agent acquire resistance to other structurally and
      functionally unrelated drugs. The classical form of MDR is caused by a plasma
      membrane protein currently named P-glycoprotein or P-170 encoded by the human mdr
      1 gene in its functional isoform. In vitro cell lines expressing P-170 usually
      also present phenotypic and functional alterations. In the present study we
      report that the cytotoxicity mediated by tumor necrosis factor alpha (TNF alpha)
      in MDR variants of the human T-lymphoblastoid CEM cell line is associated with
      apoptosis (programmed cell death). Susceptibility of MDR cells to apoptosis was
      increased upon cycloheximide + TNF alpha sequential treatment, whereby the
      impairment of protein synthesis due to the former agent was followed by the
      effect of cytokine exposure. Massive apoptosis of P-170-positive cells, but not
      of controls, was also obtained by depletion of nutrients (i.e., serum
      starvation). In contrast, TNF-alpha exerted a similar apoptotic effect in
      epithelial (MCF-7) or myeloma (S8226) drug-sensitive/ -resistant cell pairs.
      However, the MDR variant of myeloma S8226 was more sensitive to the cytostatic
      effect of TNF alpha than the parental drug-sensitive cell line. These results
      suggest that the presence of the MDR phenotype may be associated with increased
      histotype-dependent cell susceptibility to specific, protein-synthesis
      independent, apoptotic pathways.

PMID- 8760595
TI  - Scatter factor expression and regulation in human glial tumors.
AB  - Scatter factor (SF) (also known as hepatocyte growth factor [HGF]) is a cytokine
      that induces cell motility in vitro and angiogenesis in vivo. SF appears to be a
      determinant of the malignant phenotype in certain systemic cancers. We detected
      SF in extracts prepared from human gliomas, with the highest levels found in
      malignant tumors. Human glioblastoma cells expressed both SF and its receptor (c
      met protein) in vivo, as demonstrated by immunohistochemistry. Consistent with
      these observations, we found moderate to high levels of production of
      immunoreactive and biologically active SF by cultured human glioblastoma cells (3
      of 8 lines) and by neural microvascular endothelial cells (NMVEC) (3 of 3 lines).
      SF stimulated the proliferation of glioblastoma and NMVEC cell lines by paracrine
      or autocrine mechanisms. Conditioned medium (CM) from both glioblastoma and NMVEC
      cells contained SF-inducing factor (SF-IF) activity, defined by its ability to
      stimulate SF production in an indicator cell line (MRC5 human fibroblasts). This
      activity consisted of a high-molecular-weight (> 30 kDa), heat-sensitive
      component and a low-molecular weight (< 30 kDa), heat-stable component.
      Furthermore, glioblastoma CM stimulated NMVEC SF production, and NMVEC CM
      stimulated glioblastoma cell SF production, by 3- to 6-fold in each case. Our
      findings demonstrate that SF-dependent interactions between glioma cells, and
      between glioma cells and endothelium, can contribute to the heterogeneous
      proliferative and angiogenic phenotypes of malignant gliomas in vivo.

PMID- 8760596
TI  - Characterization and epitope mapping of several new anti-P-glycoprotein
      monoclonal antibodies.
AB  - Monoclonal antibodies (MAbs) were raised against partially purified Class I P
      glycoprotein from multidrug-resistant Chinese hamster ovary CHRB30 cells. Fifteen
      stable monoclonal hybridoma cell lines were established, and the secreted
      antibodies were classified into 8 groups on the basis of banding pattern on
      immunoblots of P-glycoprotein digested with cyanogen bromide or partially
      digested with proteases. One representative of each group was tested further for
      several activities. Six of the 8 recognized human P-glycoprotein in the multidrug
      resistant SKVLBI cell line. None of the antibodies recognized P-glycoprotein in
      unfixed cells, suggesting that all recognize cytoplasmic epitopes or
      extracellular epitopes not accessible in native P-glycoprotein. All 8 antibodies
      were able to immunoprecipitate P-glycoprotein from non-denaturing detergent
      solution. The linear epitopes of the antibodies were mapped to 11-27 amino acids.
      Two of the antibodies had epitopes in the linker region, 3 in the N-terminal
      nucleotide binding domain, 2 in the C-terminal nucleotide binding domain and 1 in
      the predicted cytoplasmic loop between predicted transmembrane helices 8 and 9.
      These antibodies, with known epitopes, could have uses for P-glycoprotein
      detection, structure/function studies, purification and quantitation.

PMID- 8760597
TI  - An effect of K-ras gene mutation on epidermal growth factor receptor signal
      transduction in PANC-1 pancreatic carcinoma cells.
AB  - The Ras protein is involved in tyrosine kinase signal transduction pathway steps
      such as EGFR signalling. Most human pancreatic carcinomas harbor a point mutation
      of K-ras oncogene and overexpress transforming TGF-alpha. We studied how K-ras
      gene mutation could influence the EGFR signal transduction mechanism and the
      autonomous proliferation of pancreatic carcinoma cells, using PANC-1 human
      pancreatic carcinoma line and W1-38 normal human fibroblast cell line as a
      control. PANC-1 cells responded to neither EGF nor exogenous TGF-alpha, although
      anti-TGF-alpha MAb suppressed their growth. Expression of TGF-alpha mRNA was
      detected only in PANC-1 cells, which confirmed EGFR being within an autocrine
      loop. Ras protein and MAP kinase were constitutively activated in PANC-1 cells so
      that the cells did not respond to treatment with staurosporine or herbimycin A,
      and exhibited slight response to EGF stimulation. PANC-1 cells harbored K-ras
      gene mutation in codon 12. In contrast, EGF stimulation induced an elevation of
      GTP-bound ratio to Ras protein and an activation of MAP kinase with accelerated
      growth in W1-38 cells. From these findings, we concluded that K-ras gene mutation
      possibly plays an important role in the autonomous proliferation of PANC-1
      pancreatic carcinoma cells, and that an autocrine loop represented by TGF-alpha
      and EGFR may further accelerate the growth of PANC-1 cells.

PMID- 8760598
TI  - Reflux of duodenal or gastro-duodenal contents induces esophageal carcinoma in
      rats.
AB  - Esophageal adenocarcinoma arises from Barrett's esophagus, which is induced by
      gastro-esophageal reflux. This refluxate often contains duodenal contents, whose
      backflow triggers gastric carcinoma, suggesting the hypothesis that refluxed
      duodenal contents cause esophageal carcinoma. This study examines the role of
      duodenal and gastric reflux in the absence of exogenous carcinogens in esophageal
      carcinogenesis. Wistar male rats, 120 in all, each weighing approximately 250 g,
      were used. Three experimental procedures were performed to produce gastro-duodeno
      esophageal reflux, duodeno-esophageal reflux and gastro-esophageal reflux, for
      comparison with 2 control procedures, Roux-en-Y reconstruction and a sham
      operation. The animals were fed a standard diet and were examined 50 weeks after
      surgery. While no carcinoma was found among the 16 gastro-esophageal-reflux, 11
      Roux-en-Y and 12 sham-operation animals, 10 of the 12 animals with gastro-duodeno
      esophageal reflux (83%) and 10 of the 13 with duodeno-esophageal reflux (77%)
      developed esophageal carcinoma. The difference between groups was significant (p
      < 0.001). Two animals with gastro-duodeno-esophageal reflux had esophageal double
      and triple carcinomas respectively. Of the 23 carcinomas, 16 were adenocarcinoma,
      4 adenosquamous carcinoma, and 3 squamous-cell carcinoma. Adenocarcinoma
      developed from the columnar-lined epithelium near the esophago-jejunostoma, while
      adenosquamous and squamous-cell carcinoma arose from the squamous esophagitis.
      These observations demonstrate that refluxed duodenal contents per so are
      responsible for esophageal carcinogenesis.

PMID- 8760599
TI  - Dichotomy of astrocytoma migration and proliferation.
AB  - Astrocytomas often show high rates of local invasion that lead to local
      recurrence of the disease. Histologically, the most highly invasive astrocytoma
      cells are detected in isolation rather than as nests of tumor. Our study
      attempted to determine whether the migratory response to extracellular substrates
      influences the proliferative behavior of these highly invasive cells. The
      preferential and specific migratory response of human astrocytoma cells to
      extracellular matrix proteins was assessed by a microliter scale migration assay.
      Growth curve studies on protein ligands permissive (merosin) for cell migration
      indicated that the lag phase was protracted compared with cells seeded on non
      permissive proteins (vitronectin). Once a certain cell density was reached,
      logarithmic proliferation was indistinguishable on the different proteins. The
      proliferation index of populations of cells migrating on merosin and vitronectin
      was measured by both BrdU incorporation and MIB-1 immunocytochemistry labeling.
      Cells seeded on vitronectin showed higher proliferation throughout the population
      than cells seeded on merosin. On merosin, the more migratory cells at the
      periphery were less proliferative than non-migratory cells in the central region
      of that population. The integrin-associated signal transduction protein, p125FAK,
      was heavily localized in the membrane of non-migrating cells and largely absent
      in migrating astrocytoma cells. We conclude that temporally, proliferation and
      migration are mutually exclusive behaviors. Cell density or non-permissive
      substrates that inhibit cell motility favor a more proliferative phenotype.
      Conversely, active migration suppresses cell proliferation.

PMID- 8760600
TI  - Attenuated ALK5 receptor expression in human pancreatic cancer: correlation with
      resistance to growth inhibition.
AB  - Transforming growth factor-beta (TGF-beta) receptors constitute a family of
      transmembrane proteins that bind TGF-beta ligands. In this study we assessed the
      growth responsiveness to TGF-beta 1 in pancreatic cancer cell lines and
      characterized the levels of expression of TGF-beta receptors in these cell lines
      and in human pancreatic cancer tissues. COLO 357 cells were most sensitive to the
      growth inhibitory actions of TGF-beta 1, PANC-1 cells exhibited moderate
      sensitivity, Hs766T cells exhibited slight sensitivity and MIA PaCa-2 and T3M4
      cells were resistant to TGF-beta 1. Only COLO 357 cells expressed high levels of
      ALK5, the major type I TGF-beta receptor (T beta RI). Hs766T and PANC-1 cells
      expressed high levels of SKR1, another T beta RI subtype. Only MIA PaCa-2 cells
      did not exhibit the type II TGF-beta receptor (T beta-RII) transcript, whereas
      type III TGF-beta receptor (T beta-RIII) mRNA levels were elevated in this cell
      line and in HS766T cells. All the cell lines expressed TGF-beta 1, but TGF-beta 2
      and TGF-beta 3 mRNA levels were variable. ALK5 and SKR1 mRNA levels were 6.8- and
      9-fold greater in the pancreatic tumors in comparison with the corresponding
      levels in the normal pancreas. However, in the cancer cells, ALK5
      immunoreactivity was faint, whereas T beta RII immunoreactivity was focal and
      intense. Conversely, in ductal cells adjacent to cancer cells ALK5
      immunoreactivity was strong, whereas T beta RII immunoreactivity was weak. Since
      ALK5 heterodimerization with T beta RII is crucial for TGF-beta-mediated
      signaling, our findings suggest that low levels of ALK5 in pancreatic cancer
      cells within a tumor may protect against growth inhibition.

PMID- 8760601
TI  - Hepatocyte growth factor (HGF) produced by peritoneal fibroblasts may affect
      mesothelial cell morphology and promote peritoneal dissemination.
AB  - Mesothelial cell monolayers have been reported to prevent infiltration of cancer
      cells into the peritoneum. We have previously reported that peritoneal fibrosis
      induced by gastric cancer cells prior to metastatization may provide a congenial
      environment for peritoneal metastases. In this study, we investigated the effects
      of peritoneal fibroblasts on peritoneal mesothelial cell morphology. Human
      gastric cancer (OCUM-2MD3), peritoneal fibroblast (NF-2P) and mesothelial (MS-1)
      cell lines were established in our laboratory. Histology of the peritoneum was
      investigated following intraperitoneal inoculation of serum-free conditioned
      media (SF-CM) from OCUM-2MD3 cells into nude mice. SF-CM from peritoneal
      fibroblasts was added to monolayer-cultured mesothelial cells, and their
      morphology was examined by phase-contrast microscopy. This experiment was
      conducted in the presence and absence of neutralizing antibodies against various
      factors. Mesothelial cells exposed to fibroblasts proliferation became
      hemispherical and separated from each other, while unexposed mesothelium remained
      as a flat monolayer. Cultured-mesothelial cells rounded up or exhibited a
      fibroblast-like shape following the addition of peritoneal fibroblast SF-CM. Anti
      hepatocyte growth factor (HGF) neutralizing antibody partly inhibited this
      effect. We suggest that soluble factors, such as HGF, produced by peritoneal
      fibroblasts affect the morphology of mesothelial cells in monolayers so that the
      resulting environment may become prone to the peritoneal dissemination of cancer
      cells.

PMID- 8760602
TI  - Carcinoembryonic antigen expression, antibody localisation and
      immunophotodetection of human colon cancer liver metastases in nude mice: a model
      for radioimmunotherapy.
AB  - Colorectal cancer frequently disseminates through the portal vein into the liver.
      In this study, outbred Swiss nude mice were adapted to facilitate the induction
      of liver metastases by a pre-grafting treatment with 6 Gy total body irradiation
      and i.v. injection of anti-asialo GM1 antibody. One day later, cultured LS 174T
      human colon cancer cells were injected into the surgically exposed spleen, which
      was resected 3 min later. In 48 of 65 mice, a few to several hundred liver
      metastases were macroscopically observed at dissection 3 to 4 weeks after
      transplantation. Ten of 10 mice, followed-up for survival, died with multiple
      large confluent liver metastases. By reducing the radiation dose to 4 or 0 Gy, or
      omitting the anti-asialo GM1 antibody injection, only 60%, 37% or 50% of mice,
      respectively, had visible metastases 3 weeks after transplantation.
      Carcinoembryonic antigen (CEA) measured in tumour extracts was in the mean 25.6
      micrograms/g in liver metastases compared with 9.2 micrograms/g in s.c. tumours.
      Uptake of radiolabelled anti-CEA monoclonal antibody (MAb) in the metastases 12,
      24 and 48 hr after injection gave a mean value of 39% of the injected dose per
      gram of tissue (ID/g). In comparison, MAb uptake in s.c. and intrasplenic tumours
      or lung metastases gave a mean percentage ID/g of 20, 18 and 15, respectively.
      Laser-induced fluorescence after injection of indocyanin-MAb conjugate allowed
      direct visual detection of small liver metastases, including some that were not
      visible under normal light. Preliminary results showed that mice, pre-treated
      with 4 Gy irradiation and the anti-asialo GM1 injection, were tolerant to
      radioimmunotherapy with a total dose of 500 muCi 131I labeled anti-CEA intact
      MAbs given in 3 injections.

PMID- 8760603
TI  - Induction of a cytolytic T-cell response in mice with a recombinant adenovirus
      coding for tumor antigen P815A.
AB  - We investigated the efficacy of a recombinant adenovirus in inducing a cytolytic
      T-lymphocyte (CTL) response in mice against tumor antigen P815A, which is present
      on mouse mastocytoma P815. The recombinant adenoviral vector (Adeno.PIA)
      contained the sequence coding for the antigenic nonapeptide which binds to the H
      2.Ld molecule to form antigen P815A. We verified that murine cells infected in
      vitro with Adeno. PIA were lysed by an anti-P815A CTL clone. Mice then received a
      single intradermal injection of Adeno. PIA, and after a few weeks their spleen
      cells were stimulated in vitro with tumor cells expressing antigen P815A. An anti
      P815A CTL response was observed with the spleen lymphocytes of nearly all the
      mice, providing the lymphocytes were re-stimulated in vitro with cells expressing
      both P815A and co-stimulatory molecule B7.1. When the stimulatory cells did not
      express B7.1, a specific CTL response was observed in only 45% of the mice, and
      it was less intense. The Adeno. P1A viral vector was unable to raise an anti
      P815A response in mice that had been previously infected with a recombinant
      adenovirus carrying the beta-galactosidase gene or with a defective adenovirus.
      We conclude that adenoviral vectors may be very useful for the priming of
      cytolytic T-cell responses directed against human tumor antigens. Other modes of
      immunization may be necessary to boost the responses induced with adenoviral
      vectors.

PMID- 8760604
TI  - Sulphur dioxide: a potent glutathione depleting agent.
AB  - Sulphur dioxide (SO2) is an air pollutant implicated in the initiation of
      asthmatic symptoms. Glutathione (GSH) has been proposed to play a role in
      detoxification of SO2 through the sulfitolysis of glutathione disulphide (GSSG)
      to S-sulphoglutathione (GSSO3-). Rats were exposed to concentrations of SO2
      between 5 and 100 ppm for 5 hr a day between 7 and 28 days. Lung injury as
      assessed by bronchoalveolar lavage and tissue GSH status were evaluated. SO2 5
      ppm failed to elicit any lung injury or inflammatory response but did deplete GSH
      pools in lung, liver, heart and kidney. Activities of gamma-glutamylcysteine
      synthetase (GCS), glutathione peroxidase (GPx), glutathione S-transferase (GST)
      and glutathione reductase (GRed) in lung were lowered relative to those in
      control animals. In liver, GRed activity was decreased. SO2 50 ppm exposure also
      failed to elicit injury or inflammation but did lower inflammatory cell numbers
      in the circulation. Rats exposed to 50 ppm SO2 maintained tissue GSH status, but
      activities of GCS, GPx, GRed and gamma-glutamyltranspeptidase in lung and hepatic
      GRed and GPx were significantly lower than in control rats. Unaltered GST
      activity in lung and liver was suggestive of an impairment of the sulfitolysis
      reaction in these animals, perhaps through lower substrate flux through the GPx
      reaction, as GSSO3- is a known inhibitor of GST in the rat. Rats exposed to 100
      ppm SO2 exhibited evidence of inflammation (120-fold increase in neutrophil
      numbers recovered in lavage fluid) and like the 5 ppm exposed rats had lower
      tissue GSH concentrations and GSH-related enzyme activities in lung. We conclude
      that sulfitolysis of GSSG does occur in vivo during SO2 exposure and that SO2,
      even in the absence of pulmonary injury, is a potent glutathione depleting agent.

PMID- 8760606
TI  - Effect of organic solvents on lysozyme-antilysozyme precipitin reaction.
AB  - The effect of nine organic solvents and urea on hen-eggwhite lysozyme-rabbit
      antilysozyme precipitin reaction was studied at a ratio of the antigen to the
      antibody of 1:26 by weight in 70 mM sodium phosphate buffer, pH 7.0. The organic
      solvents used were dioxane, acetonitrile, dimethylsulfoxide, N,N
      dimethylformamide, 1-propanol, propylene glycol, trifluoroethanol, ethylene
      glycol and glycerol. These solvents invariably caused reduction in the amount of
      protein precipitated during the antigen-antibody reaction. The concentration of
      an organic solvent, CM, required for 50% reduction in the precipitin reaction
      value was determined for each organic solvent. Among the nine organic solvents,
      dioxane was the most potent inhibitor of the precipitin reaction. The nine
      organic solvents did not cause irreversible inactivation of the antigen and the
      antibody, and at concentrations used in this study most of them would be
      nondenaturing. These solvents seem to destabilize the antigen-antibody complex.

PMID- 8760605
TI  - Effect of testosterone on carbonic anhydrase and MG(2+)-dependent HCO3-stimulated
      ATPase activities in rat kidney: comparison with estradiol effect.
AB  - Effects of testosterone administration (TP; 1-3 mg/kg body weight, S.C., once
      daily for 7 days) on the cytosol carbonic anhydrase (CA) and tubular brush border
      Mg(2+)-dependent HCO3(-)-stimulated ATPase (Mg(2+)-HCO3(-)-ATPase) activities of
      normal and castrated male and female rat kidney were compared with estradiol (E2)
      effects. TP decreased kidney CA activity in a dose-dependent manner in all four
      animal conditions, and negative correlations were observed between cytosol CA
      activity and serum testosterone concentration. However, brush border Mg(2+)-HCO3(
      )-ATPase activity was not affected by testosterone. Orchiectomy increased only CA
      activity and its value recovered to normal levels by 3 mg/kg TP replacement,
      whereas Mg(2+)-HCO3(-)-ATPase activity did not change. In the previous study, on
      the other hand, E2 administration activated both kidney enzymes in normal male
      rats and only Mg(2+)-HCO3(-)-ATPase in normal female rats. Testosterone and E2
      conversely affected kidney CA activity in male rats. These facts suggest that the
      cytosol CA may control kidney functions on H+ and HCO3- metabolism under the
      balance of both sex hormones in the living body.

PMID- 8760607
TI  - Perinatal astemizole exposure in the rat throughout gestation: long-term
      behavioral and anatomic effects associated with reproduction.
AB  - Astemizole (ATZ), a non-sedative antihistamine, which antagonize histamine at the
      level of H1 receptor, was administered daily to female Wistar rats as a 10-mg/kg
      dose throughout pregnancy. ATZ exposure reduced offspring body weight and delayed
      the pinna detachment and startle reflex without any modification of dams body
      weight during gestation. Long-term disruption of male reproductive behavior was
      seen in experimental animals, whereas female sexual behavior was not modified. In
      addition, no motor alterations were observed in female or males in adulthood.
      Testis wet weight was reduced, but no modifications were detected in vasa
      deferentia or seminal vesicle. We proposed that ATZ administration during
      pregnancy causes several effects mainly of a sexual nature by interfering either
      with the hormonal mechanism involved in the central nervous system
      masculinization or by a direct action of the drug on pups during the development.

PMID- 8760608
TI  - Methods for purification of glutathione transferases in the earthworm genus
      Eisenia, and their characterization.
AB  - Isoenzymes of glutathione transferase (GST) were partially purified from the
      earthworm species Eisenia andrei and E. veneta using affinity chromatography
      followed by ion exchange chromatography and reversed-phase HPLC. In E. veneta,
      five activity peaks, named EvGST Ia, Ib, II, III and IV, were separated by anion
      exchange chromatography. The GSTs in E. andrei were resolved by cation exchange
      chromatography into six groups, named EaGST I-VI. Using reversed-phase HPLC, the
      affinity-purified GSTs from E. andrei and E. veneta were resolved into 14
      subunits, named Ea1-Ea14 and Ev1-Ev14, respectively. EaGST I, II, IV and EvGST Ia
      were further characterized. These forms displayed different substrate specificity
      towards the substrates 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4
      nitrobenzene, ethacrynic acid (ETHA) and cumene hydroperoxide, as well as
      different subunit composition determined by SDS-PAGE and reversed-phase HPLC.
      EaGST IV and EvGST Ia showed exceptionally high ETHA activity compared with the
      other forms. EaGST IV consisted of a homodimeric protein involving subunit Ea6
      with an apparent molecular weight of 26.5 kDa, whereas EvGST Ia is composed of
      two different subunits (Ev9 and Ev10). Amino acid composition and N-terminal
      analysis of the first 33 residues of Ea6 indicated that the enzyme is most
      related to the pi class. Subunit Ev10 had 67% identity with Ea6, over the region
      sequenced (12 residues), but up to 90% identity with GSTs from several nematodes.
      Exposure of both species to trans-stilbene oxide, 3-methylcholanthrene and
      phenobarbital for three weeks did not elevate the activity of GST measured with
      CDNB and ETHA.

PMID- 8760609
TI  - Effect of the insect growth regulators, N-tert-butyl-N, N'-dibenzoylhydrazines,
      on neural activity of the American cockroach.
AB  - N-tert-Butyl-N,N'-dibenzoylhydrazines, agonists of 20-hydroxyecdysone,
      decelerated the rising and falling phases of an action potential, which had been
      electrically induced in the cockroach giant axon, at moderately high
      concentrations. 4-Aminopyridine, a blocker of potassium channels of nerve,
      selectively decelerated the falling phase of the action potential. This class of
      compounds caused convulsions in American cockroaches when injected. The
      convulsive activity seemed to be positively related to the activity to decelerate
      the falling phase of the action potential.

PMID- 8760610
TI  - Changes in GST-isoenzyme pattern of some organs of sheep exposed to different
      levels of pollution.
AB  - GST isonzyme patterns were studied in the cytosolic fraction of liver, kidney and
      lung of sheep exposed to industrial metal pollutants and compared with those of
      control animals. The methodology included the determination of enzymatic
      activities with several subunit-specific substrates (DCNB, NPB, EPNP and EA) and
      Western blotting using antibodies to specific rat GST subunits 1, 8 (alpha
      class), 3 (mu class) and 7 (pi class). In liver and lung, crossed reactivities
      with subunits 1 and 3 were absent in the controls but were present in exposed
      animals. Just the opposite result was obtained for subunit 8 crossed reactivity
      that was only in the control animals. In the kidney, crossed reactivities towards
      subunits 3 and 8 were absent and crossed reactivity equivalent to subunit 7 was
      present in all animals, and equivalent to subunit 1 was weakly induced in exposed
      animals. A 3.3-fold increase in the activity with NPB detected in the kidneys of
      exposed animals points to the induction of a theta class isoenzymes. Clear
      increases were found in the livers of exposed animals in the activities with CDNB
      (1.8-fold), DCNB (2.6-fold) and EPNP (2.1-fold), but no differences were found in
      the lungs with any of the substrates. The GST isoenzyme pattern of liver and lung
      could be, in principle, a useful biomarker of exposure to environmental pollution
      in sheep.

PMID- 8760611
TI  - Metabolic responses of the turkey hen (Meleagris gallopavo) to an intravenous
      injection of chicken or porcine glucagon.
AB  - The purpose of this study was to compare the metabolism of chicken and porcine
      glucagon in the turkey hen. Six hens each were infused with either porcine or
      chicken glucagon (16.6 micrograms/kg body weight). Blood samples were obtained at
      intervals pre- and post-infusion and analyzed for glucagon, glucose, insulin,
      free fatty acids, thyroxine (T4) and triiodothyronine (T3). The half-life (T 1/2)
      of porcine (4.5 min) and chicken glucagon (5.5 min) were similar. A 13% increase
      in glucose concentrations occurred within 10 min and remained elevated (22%) for
      2 hr. A concomitant increase in insulin was noted, though not significant from
      pre-injection levels. A 50% increase in free fatty acids occurred in 2 min,
      reaching a zenith at 10-15 min post-treatment, and returned to baseline by 2 hr.
      Significant (P < 0.05) decreases in the circulating concentrations of both T3 and
      T4 hormones were observed within 5-10 min post-glucagon treatment and remained
      suppressed for the duration of sampling. These data indicate that the hormonal
      and metabolic responses of female turkeys to mammalian and avian glucagon are
      similar.

PMID- 8760612
TI  - [Lung transplantation 1996].

PMID- 8760613
TI  - [Gynecological malformations. Classification and contribution of different
      imaging methods].

PMID- 8760614
TI  - [Bronchial anastomotic complications after pulmonary transplantation. X-ray
      computed tomographic evaluation].
AB  - PURPOSE: To determine the sensitivity and specificity of CT in depicting
      bronchial anastomotic complications after lung transplantation. MATERIALS AND
      METHODS: A retrospective, blinded review of 105 CT scans obtained after single (n
      = 17) or double (n = 10) lung transplantation in 27 patients was done by two
      radiologists in consensus. CT images, were analyzed with respect to the status of
      bronchial anastomoses, with three possible answers given to the readers: normal,
      dehiscence, or stenosis. CT features were correlated to bronchoscopic and follow
      up findings, which were considered as standard of reference. RESULTS: CT had a
      60% sensitivity and 98% specificity for the diagnosis of bronchial dehiscence,
      and 40% and 99% for the diagnosis of anastomotic stenosis. One case of bronchial
      disruption was diagnosed on CT scan only and subsequently confirmed by repeated
      bronchoscopy. CONCLUSION: In our study, CT has a low sensitivity but a high
      specificity in the detection of bronchial anastomotic complications after lung
      transplantation. However, CT remains useful in some cases, as it can show
      complications not seen bronchoscopically.

PMID- 8760615
TI  - [MRI and CT of parotid diseases in HIV-positive patients].
AB  - We report five cases of HIV patients with parotid pathology during a period of
      one year. All patients (4 men and 1 woman between the ages of 32 and 47 years)
      had a MRI or a CT confirmation of the parotid gland lesion. Three patients
      exhibited parotid gland cysts, one a nonspecific chronic inflammation and one an
      enlargement of the parotid gland with some benign lymphoepithelial lesions. Two
      patients underwent ultrasound-guided fine-needle aspiration biopsy. The cytology
      examination confirmed the benignity of the lesions. Finally, we expose the
      clinical management of parotid enlargements in HIV-positive patients.

PMID- 8760616
TI  - [MRI and Listeria monocytogenes rhombencephalitis].
AB  - Rhombencephalitidis is a serious form of brainstem inflammation, difficult to
      diagnose on the basis of clinical and laboratory findings alone. We describe the
      MR appearance of 3 cases of Listeria monocytogenes rhombencephalitidis and
      correlate the findings with clinical information. MR imaging is crucial for early
      diagnosis of this illness: patchy signal hyperintensity throughout the medulla
      and cerebellar peduncles on T2 weighted images, always in association with a
      hypointense dot; numerous gadolinium-enhanced microabcesses in the
      rhombencephalon. MR imaging is very useful for follow-up examinations.

PMID- 8760617
TI  - [Peritoneal mesothelioma. Contribution of MRI. Apropos of a case].
AB  - Peritoneal invasion by a malignant mesothelioma is less frequently encountered
      than pleural localization. We report a case of a double pleural and peritoneal
      localization. CT and MR may be suggestive, especially when pulmonary asbestosis
      is associated, but pathology (fine needle aspiration or surgical biopsy) is
      necessary to assess the diagnosis. When possible surgery is performed, with or
      without associated radiotherapy. Prognosis is nevertheless very poor.

PMID- 8760618
TI  - [Pseudotumoral xanthogranulomatous pyelonephritis. A propos of 2 cases].
AB  - We report two cases of xanthogranulomatous pyelonephritis observed in elderly
      women. Diagnosis before surgery is difficult. CT is the best single examination.

PMID- 8760619
TI  - [Value of echography in a case of polyorchidism].
AB  - We report a case of polyorchidism diagnosed by scrotal ultrasonography and
      confirmed by surgery. Sixty eight cases have been reported in the literature.

PMID- 8760620
TI  - [Mullerian adenosarcoma].

PMID- 8760621
TI  - [Indexing in radiology and medical imaging].

PMID- 8760622
TI  - [Doppler and testicular torsion].

PMID- 8760623
TI  - [Teleradiology in the USA. The pros and cons].

PMID- 8760624
TI  - [Cardiovascular risks during isokinetic tests for peripheral functional studies].
AB  - OBJECTIVES: Isokinetic tests used to assess both muscle function and joint
      disorders stimulate the entire organism and in particular the cardiovascular
      system. We evaluated the risk of cardiovascular or vascular impairment during
      isokinetic knee extension and flexion tests. METHODS: Cardiac electrical
      activity, heart rate and systolic and diastolic blood pressures were measured in
      251 patients during 50-sec isokinetic tests. RESULTS: Abnormal findings were
      recorded in 15 patients (5.9%) including 6 with altered blood pressure, 4 with
      altered cardiac electrical activity and 5 with heart rate abnormalities. Maximal
      heart rate for a given subject recorded during the isokinetic test was 199 beats
      per minute and heart rate exceeded 190 bpm in 92 subjects (36.6%). Maximal
      efforts with cardiac barometric charge produced dramatic, occasionally
      pathological, changes in heart rate or blood pressure. CONCLUSION: These findings
      emphasize the need to carefully assess patients before isokinetic tests and
      carefully monitor cardiovascular parameters. A preliminary physical examination
      and medical surveillance during testing are required.

PMID- 8760625
TI  - [Fatal pulmonary embolism. Risk factors and anatomo-pathological findings related
      to gender and age].
AB  - OBJECTIVES: The aim of this study was to evaluate possible variations in clinical
      risk factors and anatomopathological findings in fatal pulmonary embolism in
      relation to sex and age. METHODS: The total sample consisted of 230 subjects
      (mean age 72 +/- 11 years), 103 males and 127 females, of which 74 died out-of
      hospital and 156 in the course of hospitalization. 124 cases were then considered
      also separately as "sudden death group". The sample was stratified by sex and
      into 4 groups by age: subjects aged less than 60 years, between 60 and 69,
      between 70 and 79, and more than 80 years. RESULTS: Age at occurrence of
      pulmonary embolism was significantly higher in females, compared with males (75
      +/- 11 vs 69 +/- 11 years, p < 0.001), and the men/women ratio was higher in
      younger age groups, tending to inversion with aging. An increased frequency of
      males was found between subgroups of subjects affected by valvular heart disease
      (10.6% vs 2.3%, p = 0.019), and chronic pulmonary disease (7.7% vs 1.8%, p =
      0.049), whereas an increased frequency of women was found in a group of subjects
      suffering from trauma or fracture (12.6% vs 2.9%, p = 0.016). As concerns age
      subgroups, a significant increased frequency of subjects aged < 60 years was
      found in risk groups "surgery" (36%, p < 0.001) and "malignancy" (40%, p =
      0.002). Moreover, in subjects aged less than 80 years, main predisposing factors
      were recent trauma and/or a fracture (16.2%, p = 0.013). CONCLUSION: The
      difference in frequency of risk factors between sexes could depend on the higher
      life expectancy in women, with consequent increase in likelihood of risk factors
      specifically related to the elderly.

PMID- 8760626
TI  - [Contraception with levonorgestrel subdermal implants. A Tunisian study].
AB  - OBJECTIVES: We report our experience in Tunisia with contraception by subdermal
      levonogestrel implants. METHODS: From January 1, 1990 through June 30, 1994 we
      inserted 1021 implants at our family planning center in Ariana. RESULTS: Our
      experience with this pure progesterone implant showed that this method provides
      effective long-duration contraception. There was only one case of ectopic
      pregnancy among our 1021 patients. The most frequent undesirable effect and the
      first cause of discontinuing treatment was disturbed menstrual cycle with
      irregular discharge. CONCLUSION: Our results underline the importance of
      counselling before implant insertion. A 10-day estrogen regimen may provide a
      solution for menstrual disorders.

PMID- 8760627
TI  - [Nephrotic syndrome complicating treatment with interferon alpha].
AB  - We report two cases of nephrotic syndrome with minimal glomerular change
      complicating alpha-interferon therapy. CASE REPORTS: The first patient was a 60
      year-old man with Waldenstrom's disease who was given 1 million units of alpha
      interferon three times a week for 22 months. Acute renal failure developed when a
      second protocol was started. Renal biopsy revealed intraglomerular deposits and
      no cellular proliferation. Total remission could not be achieved with
      corticosteroids. The second case was a 46-year-old man given high dose alpha
      interferon (15 million units 3 times a week) for lymph node metastasis of a
      malignant melanoma. A nephrotic syndrome without renal failure developed during
      the third month of treatment. Minimal glomerular involvement was seen.
      Symptomatic treatment led to resolution of the nephrotic syndrome. DISCUSSION:
      Nine other cases of nephrotic syndrome complicating alpha-interferon therapy have
      been reported in the literature.

PMID- 8760628
TI  - [Medical environment of total hip prosthesis].
AB  - Total hip replacement is an extremely frequent operation for the treatment of
      degenerative joint disease. Indication for surgery must take into account the
      patient's general status, associated diseases, multiple joint involvement, and
      the efficacy and tolerance to medical treatments. The decision to operate is
      taken together by the physician and the patient. The degree of functional
      impairment and the patient's age are important factors. The patient must be
      informed that the period of hospitalization will be approximately 15 days and
      that good results are obtained in approximately 98% of the cases. Preoperative
      consultation with the anesthesist will focus on associated diseases with special
      attention to possible infectious foyers. Early post operative care includes a 48
      hour antibiotic reginien, thromboprophylaxy with low molecular weight heparin for
      3 days followed by anti-vitamin K for 6 weeks, and non-steroid antiinflammatory
      drugs for 5 days of up to 6 weeks in case of suspected risk of ossification. At
      mid-term, complications may include hematomas, infection and luxation. The
      fixation may also fail in certain cases where transtrochanter access was used.
      Long-term follow-up monitors for possible late onset infection and late luxations
      which usually result from prosthesis wear and more rarely from muscular causes.

PMID- 8760629
TI  - [Treatment of heart failure].
AB  - Heart failure is a disease which involves not only the heart but the entire
      circulatory system. Progression is directly related to interactions between
      myocardial disorders and neurohormonal and circulatory phenomena. Advances in
      treatment have resulted more from the development of vasodilator drugs with
      neurohormonal effects than from drugs with a direct effect on the myocardium.
      Diuretics are essential due to their rapid functional effect and the reduction in
      pressure on the ventricle wall. The effectiveness of digitalics is recognized not
      only in patients with atrial fibrillation, but also in those in sinus rhythm with
      ischemic heart disease. Conversion enzyme inhibitors are useful in all stages of
      heart failure, improving both quality of life and life expectancy as well as
      limiting myocardial and vascular remodeling and retarding progression of
      ventricular dysfunction. As current progress in the treatment of heart failure
      has not greatly reduced mortality, prevention is the major challenge facing all
      physicians. Treatment of asymptomatic ventricular function is one rational
      approach.

PMID- 8760630
TI  - [Surgically treated chronic bilateral Achilles tendon disease, without
      spontaneous rupture, caused by perfloxacin].

PMID- 8760631
TI  - [Relation between chronic gastritis, Helicobacter pylori and HLA: role of DQA1
      and DQB1 molecular alleles].

PMID- 8760632
TI  - [Antiphospholipid antibodies and deep venous thrombosis in hemorrhagic
      rectocolitis disclosed by pyoderma gangrenosum].

PMID- 8760633
TI  - [Paragonimus westermani pulmonary distomatosis in Gabon. First case].

PMID- 8760635
TI  - [Massive transfusion in cancer surgery. A study of the survival of 21 patients].
AB  - In a retrospective study over 5 years, the evolution of 21 patients who received
      a massive blood transfusion during a carcinological surgery was analyzed. In this
      type of surgery, the frequency of massive blood transfusion is 0.28% and affects
      2.5% of the patients transfused. In half of the cases, surgery was performed to
      resect an ovarian cancer. The overall death rate, related to the importance of
      the blood transfusion, is high: 38% (8 patients out of 21). Among the patients
      who survived (13), the actuarial survival is low: 10 deaths from local or
      metastatic disease with a mean survival of 12 months, suggesting that the use of
      massive blood transfusion was related to the tumoral aggressiveness and to the
      severity of the deepseated malignant disease.

PMID- 8760636
TI  - [Analgesia in surgery of the foot. Apropos of 1373 patients].
AB  - This retrospective study concerns 1,373 adult patients who underwent forefoot
      surgery during 1988-95 under regional anaesthesia by ankle nerve blocks (of
      posterior tibial nerve systematically and other nerves according to the surgical
      site). As a rule, plain bupivacaine 0.5% (maximum 40 mL) was used, completed if
      necessary by lidocaine 1% (a few mL). A nerve stimulator is currently used for
      posterior tibial blocks. About 50% of indications (such as hallux surgery)
      require short hospitalization (3 days). A catheter is inserted near to the
      posterior tibial nerve by the surgeon, allowing postoperative reinjections of 10
      mL of bupivacaine 0.25% every 6 hrs by nurses, for 1-2.5 days. Other patients
      undergoing minor procedures (material removal, cysts, exostosis, etc.) can be
      operated on a day-care basis, without postoperative analgesic injections. Results
      were very satisfactory for both patients and surgeons. No general anaesthesia was
      needed (except after one case of convulsions, likely from accidental injection of
      a few mL of local anaesthetic and without any sequelae). Five patients complained
      of temporary paraesthesias, with indication of a posterior tibial neurolysis in
      one case and complete recovery. Thus ankle blocks appear increasingly to be a
      satisfactory alternative to general anaesthesia for most surgical procedures on
      the forefoot, provided that all usual safety conditions are respected and the
      patient's acceptance of the procedure is obtained.

PMID- 8760634
TI  - [Tetraplegia after benign neck injury in cervical arthrosis. Value of high-dose
      corticoid treatment].

PMID- 8760637
TI  - [Sciatic nerves block].
AB  - Sciatic nerve block is considered difficult to perform, but very useful for lower
      limb anaesthesia and analgesia. The use of a nerve stimulator makes the technique
      easier. Functionally, it is better to consider that there are three independent
      sciatic nerves, namely, the posterior cutaneous nerve, the tibial nerve and the
      common peroneal nerve. Searching for blocking these three nerves and especially
      the latter two, specifically improve the reliability and quality of blockade.

PMID- 8760638
TI  - [Epidural anesthesia for labor].
AB  - Since the last decade, lumbar epidural analgesia has gained widespread use in
      obstetrics. Approximately 80% of parturients receive epidural analgesia for
      labour and vaginal delivery as well as caesarean section in most centres. There
      is little doubt that the most successful application of epidural analgesia during
      labour, considered by more than 75% of primiparas as extremely painful. The
      quality of analgesia is far superior to that which can be achieved by either
      parenteral or inhalation approaches and, unlike these methods, the mother remains
      alert. Epidural analgesia also prevents, or greatly diminishes, most of the
      physiological and chemical responses to labour pain that can be considered as
      stress responses, similar to those that have been described during surgery. There
      are considerable benefits, therefore, to both mother and child. Thus, epidural
      analgesia usually can be extended to relieve both uterine pain and pain related
      to distension of the lower birth canal, as well as providing analgesia for
      forceps delivery or caesarean section. Epidural analgesia allows the mother to be
      awake, minimizes or completely avoids the problems of maternal aspiration and
      avoids neonatal drug depression from general anaesthetics. If the most popular
      indication for epidural analgesia is the provision of pain relief, there are
      certain complications of pregnancy in which epidural analgesia appears to be
      indicated on therapeutic grounds such as pregnancy-induced hypertension, breech
      delivery, multiple pregnancy, incoordinate uterine action and fetal and/or
      maternal medical complications.

PMID- 8760639
TI  - [Modified technique of Waters for retrograde intubation. Apropos of a case of
      difficult intubation].
AB  - The authors describe a case of impossible intubation by classical means in an
      obese 37-yr old woman, affected with encephalopathy, hydrocephalus and severe
      psychomotor retardation. After failure of intubation by classical methods using a
      flexible introducer, the patient was intubated by Waters retrograde technique
      using an epidural catheter passed through the thyrocricoid membrane and recovered
      in the mouth. Following this guide the endotracheal tube passed the glottis
      fairly easily with the help of a flexible "mouse tail-ended" introducer (C
      Mettro, Cook, 19.0.80) inserted into the same tube to facilitate alignment of
      distal tube and trachea. The authors conclude that the combination of epidural
      catheter and flexible introducer may facilitate the retrograde technique
      performance; they consider this technique to be an interesting alternative when
      endotracheal intubation is difficult or impossible by usual methods.

PMID- 8760640
TI  - [Hyperammonemia encephalopathy after ureterosigmoidostomy].
AB  - Ureterosigmoidostomy (USS) for bladder cancer is an attractive surgical technique
      for the improved quality of life provided to the patient, notably from a
      preserved body image. Complications, however, can jeopardize this result. We
      report the case of a woman who developed an hyperammonemic encephalopathy after
      USS "Mainz pouch II". We discuss the indication of a liver needle biopsy before
      USS when hepatic functions are abnormal and we stress the importance of regular
      "rectal exonerations" during the day.

PMID- 8760641
TI  - [Laparoscopy disclosing myocardial ischemia].

PMID- 8760642
TI  - [Combined spinal and epidural anesthesia or epidural anesthesia in obstetrics?].

PMID- 8760643
TI  - [Prevention of postoperative nausea and vomiting by lorazepam].
AB  - This study was carried out to assess the efficacy of oral lorazepam on
      postoperative nausea and vomiting in patients undergoing thyroid surgery. Twenty
      six patients were randomly assigned to two groups, and receiving orally, one hour
      before induction of anaesthesia, either 2.5 mg of lorazepam (n = 13) or a placebo
      (n = 13). Lorazepam reduced the incidence and especially the intensity of nausea.
      The incidence of vomiting in the lorazepam group was significantly lower than in
      the placebo group (14.5% vs 45%). The use of lorazepam for premedication thus
      reduces the incidence of postoperative nausea and vomiting. The advantages of
      this benzodiazepine are its ease of use, low cost and very low incidence of side
      effects.

PMID- 8760644
TI  - [Probable effect of hemofiltration on hemodynamics and tissue oxygenation in
      shock secondary to severe malaria].
AB  - The authors report a case of severe Plasmodium falciparum malaria in a French
      Guyana endemic area with secondary myocardial dysfunction treated by usual
      symptomatic therapy and continuous veno-venous haemofiltration (CVVH).
      Haemodynamic investigations revealed hyperkinetic shock and oxygen supply
      dependence. Haemodynamic remained critical under conventional therapy and CVVH
      was introduced. Haemodynamic parameters improved rapidly with reduced oxygen
      debt. In the absence of associated bacterial, viral and fungal infections, the
      systemic inflammatory response syndrome with shock and impairment of
      consciousness seems to be linked to severe Plasmodium falciparum malaria. The
      benefits and the probable mechanisms of action of CVVH are discussed.

PMID- 8760645
TI  - [Sequential anesthesia-analgesia].
AB  - Combined spinal-epidural anaesthesia (CSEA) is realized by one route immediately
      before the surgical procedure. It consists of: -a spinal anaesthesia for the
      operation itself. -followed by the installation of a catheter in the epidural
      space, so as to ensure postoperative analgesia. CSEA is a simple and attractive
      technique which requires only a good knowledge of its two components by the
      anaesthetist and the use of appropriate needles. Main indications are low abdomen
      surgery and major procedures on the lower limb. Real contra-indications are few.
      Updated recent needles could certainly extend the field and general use of this
      technique.

PMID- 8760646
TI  - [Spinal analgesia for labor].
AB  - Combined spinal epidural (CSE) analgesia for labour is usually performed with
      sufentanil (or fentanyl) which provides powerful and fast onset pain relief (< or
      = 5 min). Dose reduction of sufentanil from 10 to 5 micrograms may be recommended
      and has little influence on the 1.5-2 hours of analgesia usually obtained. This
      mean duration of action may be prolonged by half an hour with the addition of a
      low dose of bupivacaine (< or = 2.5 mg). CSE analgesia using this association has
      an elective indication when labour is advanced (cervical dilation > or = 6 cm)
      because intrathecal sufentanil alone becomes insufficient at this stage and
      standard epidural analgesia has the drawback of delayed onset. Motor blockade is
      also very uncommon during intrathecal analgesia and this benefit partly persists
      while using the epidural. In contrast, intrathecal analgesia and standard
      epidural analgesia carry a comparable risk of maternal hypotension. Mild pruritus
      is the sole side-effect often encountered. The only real concern during
      intrathecal analgesia is the reliability of the epidural location of the catheter
      when an emergency Ceasarean section is needed. Major improvement will be to
      prolong the excellent pain relief provided by intrathecal analgesia throughout
      the whole labour. This will require prolonging substantially the intrathecal
      analgesia duration and/ or influencing positively the epidural analgesia used
      afterwards. However, women prefer CSE technique to standard epidurals because of
      faster onset, less motor block, and feelings of greater self-control.

PMID- 8760647
TI  - [History of anesthesia: nitrous oxides and their historical onset].

PMID- 8760648
TI  - [History of anesthesia: the return of nitrous oxide].

PMID- 8760649
TI  - [History of anesthesia: Frederic Hewitt and nitrous oxide anesthesia].

PMID- 8760650
TI  - [Activated protein C resistance and mutation of coagulation factor V].

PMID- 8760651
TI  - [Prognostic factors of prosthetic valve endocarditis. Apropos of 122 cases].
AB  - The prognostic factors of 122 patients suffering from prosthetic valve
      endocarditis between 1978 and 1992 were studied by univariate and multivariate
      analysis. The principal causative organisms were Staphylococcus aureus (33%),
      streptococci (20%), coagular-negative staphylococci (12%), enterococci (10%) and
      gram-negative bacilli (9%). The 4 month survival rate was 66% (42 deaths). The
      main predictive factor for death was infection with S. aureus (75% vs 15% with
      other organisms). In S. aureus infection, multivariate analysis identified the
      following predictive factors for death: a prothrombin ratio less than 30% (RR =
      8.3), mediastinitis (RR = 4.9), cardiac failure (RR = 4.4) and septic shock (RR =
      2.6). In cases of infection with other organisms, the following factors were
      predictive of death: a prothrombin ratio of less than 30% (RR = 32.26), renal
      failure (RR = 7.31) and cardiac failure (RR = 6.07). In patients with S. aureus
      infection, survival was better after than without surgery: 9/20 (45%) versus 0/20
      (p < 0.001). In infection with other organisms, there was no difference in a
      survival after surgical (89%) or medical therapy (81%). Chronic endocarditis
      relapses over 1 to 5 years was observed in 9 cases. All patients were reoperated
      a total number of 18 times with 5 deaths. Very prolonged antibiotic therapy is
      recommended in these patients. The authors conclude that endocarditis not due to
      S. aureus and without complications may be treated medically. Rapid reoperation
      is necessary in all other cases.

PMID- 8760652
TI  - [Long term results of the surgical treatment of obstructive hypertrophic
      cardiomyopathies].
AB  - Between January 1973 and December 1993, 66 patients underwent surgery in our
      department for hypertrophic obstructive cardiomyopathy; mean basal outflow
      gradient was 48.4 +/- 36 mmHg, 20 patients had mitral valve lesions. Thirty six
      patients underwent myotomy-myomectomy alone, 13 mitral valve replacement alone,
      and 17 both myotomy-myomectomy and mitral valve replacement. The 30-day mortality
      rate was 7.5% for all patients; predominant risk factors were gender (female),
      greater cardiothoracic ratio, preoperative episodes of atrial fibrillation and
      lack of syncope. Overall survival rate (operative mortality included) was 65.3 +/
      8.6% at 13 years. Predominant risk factors for late mortality were the same than
      above, plus mitral valve replacement; so mitral valve repair, whenever feasible
      should be undertaken. Forty nine patients are still followed up: 46 are
      asymptomatic; Doppler mean basal outflow gradient was reduced to 10 +/- 1.4 mmHg.
      In conclusion, surgery relieves symptoms and outflow obstruction, and allows
      mitral valve reconstruction.

PMID- 8760653
TI  - [Value of dobutamine echocardiography in the detection of coronary disease in
      heart transplant patient. Groupe de Recherche VACOMED].
AB  - The value of Dobutamine stress echocardiography in the detection of coronary
      artery disease in heart transplant patients was studied in 64 patients at control
      coronary angiography 39 +/- 14 months after transplantation. Dobutamine was
      infused at progressively increasing doses (5 to 40 micrograms/kg/min) at 5 minute
      intervals, in order to reach 85% of the theoretical maximal heart rate or an
      ischaemic event. Echocardiography was analysed in the 4 standard views which were
      digitised allowing calculation of a regional wall motion score under basal
      conditions and at peak dosage in 16 left ventricular segments. Coronary
      angiography identified three groups: group I: 29 patients with normal coronary
      arteries; group II: 17 patients with non-significant coronary disease (diffuse or
      localised stenosis < 50%); group III: 9 patients with significant (> 50%)
      coronary disease. Dobutamine stress echocardiography showed regional wall motion
      abnormalities in 2/29 patients in group I, 13/17 patients in group II and all
      patients in group III (global sensitivity: 85%; specificity: 97%). The
      contractility score was significantly higher under basal conditions in group III
      (1.45 +/- 0.54) than in group I (1) and group II (1.17 +/- 0.23). At peak dose,
      the contractility score was unchanged in group I and increased significantly (p <
      0.01) in the other two groups. The authors conclude that Dobutamine
      echocardiography is a reliable, non-invasive method of detecting coronary disease
      in cardiac transplant patients, and is particularly valuable for demonstrating
      myocardial ischaemia related to coronary lesions judged to be not significant at
      coronary angiography.

PMID- 8760654
TI  - [Value of transesophageal echocardiography in post-infarction septal ruptures].
AB  - The role of transoesophageal echocardiography in the diagnosis of ventricular
      septal defect in the acute stage of myocardial infarction, was evaluated in 15
      consecutive patients (10 men and 5 women) with a mean age of 72 years in the
      period between June 1991 and April 1995. The patients had 11 anterior infarcts
      and 4 inferior infarcts with extension to the right ventricle. One patient was in
      Killips class I,7 patients in class II, 2 in class III and 5 in class IV. Only 8
      of the 15 septal ruptures could be visualised directly by conventional
      transthoracic echocardiography, though all 15 were suspected from continuous
      Doppler and colour Doppler analysis. Transoesophageal echocardiography was
      successfully performed in 14 of the 15 patients with a monoplane probe in 11
      cases and a multiplane probe in 3 cases. The average duration of the procedure
      was 12 minutes and clinical and haemodynamic tolerance was good. Ventricular
      septal defect was directly visualised in all cases in the short axis transgastric
      view and in 7 cases in transoesophageal views. Transoesophageal echocardiography
      was concordant with peroperative findings with regards to the site of ventricular
      septal defect (8 apical, 5 postero-basal and 1 median), their type (6 punched-out
      defects, 5 fissures, and 3 perforated aneurysms), their size (average 9.3 mm),
      their number with 5 multiple defects, and associated lesions (4 right ventricular
      extensions, 4 hemopericardiums and 1 free wall fissure). Transoesophageal
      echocardiography completes traditional transthoracic echocardiographic
      examination in the diagnosis of post-infarction ventricular septal defect. It is
      well tolerated and, in the authors' experience, allows limitation of invasive
      procedures to coronary angiography alone.

PMID- 8760655
TI  - [Left ventricular diastolic function: value of its study with mitral and
      pulmonary venous Doppler phonocardiography and apexography].
AB  - The study of mitral flow and pulmonary venous flow by Doppler provides a non
      invasive method of assessing diastolic function. But there are difficulties in
      differentiating normal pattern from "pseudo-normal" (Appleton Type II) (E/A
      Mitral > 1). Phonocardiography enables the recording of early (B3) and late (B4)
      diastolic gallops. The apexogramme enables calculation of the a/H and D/H ratios
      (amplitude of the "D" wave resulting from rapid early diastolic filling to the
      total amplitude of the apexogramme). These two techniques record pulsatile
      phenomena ("pulse waves") arising from variations in intra-left ventricular
      pressure. They may complete the interpretation of Doppler recordings of
      velocities of blood flow ("flow waves"). To evaluate the value of each technique,
      the authors studied left ventricular diastolic function by Doppler
      phonocardiography and apexography in 60 subjects (38 patients of which 30 with
      ischaemic heart disease, and 22 healthy subjects). The results showed that
      increase in velocity and deceleration slope of the Doppler mitral E wave was
      associated with the presence of a B3 and correlated (r = 0.60; p = 0.0001) with
      the D/H ratio of the apexogramme. On the other hand, the absence of correlation
      between the mitral A wave velocity and a B4 associated with an increased a/H
      ratio enables the differentiation of normal Doppler mitral flow (absence of B4,
      Doppler a/H ratio < 12%) from pseudo-normal appearances (B4, a/H ratio > 12%).
      Therefore, the evaluation of diastolic function by Doppler mitral and pulmonary
      venous flow analysis may be usefully completed by phonocardiography and
      apexography.

PMID- 8760656
TI  - [Survey on the practice of antibiotic prophylaxis of infective endocarditis by
      dentists].
AB  - The authors undertook an enquiry among 287 dentists to assess their practice of
      prophylactic antibiotic therapy against infectious endocarditis. Of the 227
      dentists who replied, most (90%) knew that a dental extraction required
      prophylactic antibiotic therapy. They correctly prescribed antibiotics to
      prosthetic valve patients (84%) and to those with post-rheumatic cardiac disease
      (87%). Many dentists considered that coronary bypass (66%), mitral valve prolapse
      without mitral regurgitation (65%) or chronic myocardial infarction (68%) also
      required antibiotic prophylaxis, contrary to published recommendations. Only 21%
      of dentists used the recommended 3 gram dose of amoxicillin; the others
      prescribed a lower dose or another antibiotic. Approximately half the dentists
      started treatment 1 to 3 days too soon and less than 5% used the recommended
      single dose of antibiotic. These results show that dentists do not adhere
      strictly to the rules of prophylaxis on infectious endocarditis defined by
      different working groups. The authors make several suggestions to improve the
      prevention of infectious endocarditis and to remedy the problems shown up by this
      study.

PMID- 8760657
TI  - [Value of spiral computed tomography with three-dimensional reconstruction in the
      investigation of renal arteries. An initial clinical experience apropos of 16
      cases].
AB  - Renovascular hypertension represents 1 to 2% of all causes of hypertension. It is
      important to make the diagnosis as radical treatment may be proposed. Digitised
      arteriography is the reference diagnostic method. Spiral angiotomography is a new
      diagnostic technique for the investigation of the aorta and its branches. The
      examination was performed with a Siemens Somatom Plus S spiral scanner. The
      images were acquired after intravenous injection of 140 ml of iodine contrast
      medium in the forearm. Three dimensional reconstruction of the renal arteries may
      be performed secondarily. The results of 16 examinations were compared with those
      of arteriography. Nine stenoses were suspected after spiral angiotomography and
      confirmed in 7 cases by arteriography (sensitivity 100%; specificity 77%); two
      adrenal abnormalities were also detected by spiral tomography. In this series,
      spiral angiotomography detected all cases of renal artery stenosis with good
      specificity. Moreover, this investigation also allowed evaluation of the adrenal
      glands. The simple, non-invasive and polyvalent nature of this method should, if
      the results are confirmed in a large series, lead to its use as the investigation
      of first intention for suspected secondary causes of hypertension.

PMID- 8760658
TI  - [Influence of the duration of recording in the reproducibility of the signal
      averaged electrocardiogram].
AB  - The authors studied the possibility of improving the reproducibility of the
      signal averaged ECG by increasing the number of averaged QRS complexes. One
      hundred patients were included in the study. In each cases, 400 QRS complexes
      were recorded on twice, consecutively, in strictly identical conditions. During
      each recording, the total duration of the amplified and averaged QRS complex
      (tQRS), the duration of the terminal signal below 40 microV (LAS) and the root
      mean square of the amplitude of the last 40 ms (RMS) were determined for 100,
      200, 300 and 400 recorded QRS complexes. The presence of late potentials was
      defined as the positivity of two of the following criteria: tQRS > 114 ms, LAS >
      38 ms, RMS < 20 microV. The number of contradictory diagnostic conclusions
      between two successive recordings of the same duration decreased progressively
      with the number of averaged QRS complexes: 10 for 100 QRS, 10 for 200 QRS, 9 for
      300 QRS and 6 for 400 QRS complexes, but this improvement was not statistically
      significant. The absolute differences of tQRS and RMS between two successive
      recordings of the same duration were statistically different for the four
      durations of recording (p = 0.05) and there was a tendency towards statistical
      significance for LAS (p = 0.09). The best quantitative reproducibility of the 3
      parameters was obtained with the recording of 300 QRS complexes. In conclusion,
      the reproducibility of the signal averaged ECG is improved when the number of
      average QRS complexes is increased. The authors' results suggests that
      reproducibility this is optimal with the amplification and averaging of 300 QRS
      complexes.

PMID- 8760659
TI  - [Complete atrioventricular block, a possible complication of radiofrequency
      ablation of reciprocating nodal tachycardia].
AB  - Radiofrequency ablation of the slow pathway of the reentry circuit is the usual
      radical treatment of nodal tachycardia. It is, however, possible to create
      atrioventricular conduction defects, the significance of which is not known. The
      aim on this study was to report the history of these conduction defects created
      during ablation of the slow pathway of the intranodal reentry circuit. Four cases
      were observed in a series of 27 patients. In one female patient, complete
      atrioventricular block was observed for 5 minutes before conduction returned to
      normal followed by recurrence of the tachycardias. Three other women developed
      complete atrioventricular block one to four days after the ablation. The block
      regressed after a maximum delay of 7 days. Six months to one year after the
      procedure, these three patients remain free of tachycardia and have only first
      degree atrioventricular block on the surface ECG. These patients were not
      implanted with a pacemaker. The authors conclude that complete atrioventricular
      block after ablation of the slow pathway may be treated conservatively, providing
      it is well tolerated. It normally regresses within few days.

PMID- 8760660
TI  - [Treatment of cardiac failure with angiotensin-converting enzyme inhibitors and
      diuretics].
AB  - Congestive cardiac failure is characterised by redistribution of blood flow to
      the brain and the heart at the expense of the kidneys. The prognosis of this
      condition at its most advanced stage (stage IV) is poor with a mortality of about
      50% at 5 years. The reduction of renal perfusion will lead to stimulation of all
      vasoconstrictor and anti-natiuretic mechanisms, and to a parallel activation of
      vasodilator and natiuretic systems. There is, therefore, a clear conflict of
      interest between the heart, which attempts to preserve its perfusion and
      function, and the kidneys which aggravate the haemodynamic disturbances by salt
      and water overload and the risk of arrhythmias due to hypokalaemia and
      hypomagnesaemia. The diuretics and ACE inhibitors are essential therapeutic
      classes for the treatment of congestive cardiac failure. The prevention of the
      secondary effects of diuretics and ACE inhibitors on renal function, serum
      sodium, potassium and magnesium concentrations, is based on an initial low dose
      prescription, the detection and correction of risk factors and strict clinical
      and biological surveillance. In order to avoid the risks of hyperkalaemia during
      the association of ACE inhibitor and diuretic therapy with a potassium sparing
      agent, the initial dose of these two drugs should be as low as possible.

PMID- 8760661
TI  - [Activated protein C resistance: role in venous and arterial thrombosis].
AB  - Activated protein C resistance is the most prevalent cause of thrombophilia: it
      is found in 20% to 30% of patients with a history of deep venous thrombosis
      history. Activated protein C resistance is due to an arginine 506 to glutamine
      mutation in factor V. This mutation prevents normal inactivation of activated
      factor V by activated protein C. The estimated increase in relative risk of
      venous thrombosis is 5 to 10 fold in heterozygotes, and 50- to 100- fold in
      homozygotes. Activated protein C resistance does not seem to play a role in
      arterial thrombosis or in the occurrence of myocardial infarction.

PMID- 8760662
TI  - [Guidelines of the French Society of Cardiology on the training of specialists in
      coronary angiography and angioplasty, the organization and the equipment of
      coronary angiography and angioplasty centers. Groupe de travail Angiographic et
      Cardiologie Interventionnelle Groupe de Reflexion et d'Ethique].

PMID- 8760663
TI  - [Aneurysms of the left ventricle without atheromatous coronary artery disease.
      Apropos of 2 cases].
AB  - Left ventricular aneurysms are usually secondary to myocardial infarction with
      atheromatous coronary artery disease. The authors report two rare cases of non
      atheromatous left ventricular apical aneurysms. The first case was clearly post
      traumatic but the diagnosis in the second case was more difficult. The authors
      discuss the aetiological diagnosis of these rare non-atheromatous aneurysms in
      adults and the therapeutic management with respect to these two cases and a
      review of the literature.

PMID- 8760664
TI  - [Right-to-left interatrial shunt with normal pulmonary pressures after
      pneumonectomy. Apropos of a case with severe cyanosis following left
      pneumonectomy].
AB  - Atrial septal defects usually give rise to left-to right in the absence of
      obstruction of the pulmonary outflow tract or pulmonary hypertension. The authors
      report a case of atrial septal defect with a right-to-left shunt despite normal
      pulmonary pressures at catheterisation in a 56 year-old-man who had undergone
      left pneumonectomy 6 months previously. The shunt was responsible for major
      arterial desaturation aggravated by the left lateral or dorsal decubitus
      position. Surgical closure of the defect resulted in cure with disappearance of
      cyanosis and normalisation of blood gases. The physiopathological mechanisms of
      these right-to-left shunts with normal pulmonary pressures are discussed with
      reference to previously reported cases in the literature.

PMID- 8760665
TI  - [Hyperthyroidism associated with pulmonary hypertension].
AB  - The association of pulmonary hypertension and polyendocrinopathies or connective
      tissue diseases has been reported by several authors. The causes of this form of
      pulmonary hypertension are not clear but an autoimmune process has often been
      proposed. The authors report a case of non-autoimmune hyperthyroidism and
      reversible pulmonary hypertension after total thyroidectomy and normalisation of
      thyroid function. This case supports the hypothesis of a non-autoimmune aetiology
      of some causes of pulmonary hypertension in diseases of the thyroid.

PMID- 8760666
TI  - [A large kidney with lymph nodes].

PMID- 8760667
TI  - [Convulsions in a patient treated for ovarian adenocarcinoma].

PMID- 8760668
TI  - [Right internal jugular venous thrombosis in a young women 32 years of age].

PMID- 8760669
TI  - [Fever, partial pituitary insufficiency and interstitial lung syndrome in a 35
      year-old woman].

PMID- 8760670
TI  - [Recurrent prolonged fever].

PMID- 8760672
TI  - [Is water hepatotoxic?].

PMID- 8760671
TI  - [An uncommon case of thrombopenic purpura].

PMID- 8760673
TI  - [A confused history].

PMID- 8760675
TI  - [Normal and pathological aspects of respiration during sleep].

PMID- 8760676
TI  - [Excess and lack of sleep: symptoms not to be neglected].

PMID- 8760677
TI  - [Sleep and neurotransmitters].

PMID- 8760678
TI  - [Natural history of Chlamydia infections].

PMID- 8760679
TI  - [Diagnostic methods of Chlamydia infections].

PMID- 8760680
TI  - [Chlamydia trachomatis infection in women].

PMID- 8760681
TI  - [Clinical manifestations of Chlamydia pneumoniae infections].

PMID- 8760682
TI  - Chlamydia pneumoniae and atherosclerosis.

PMID- 8760683
TI  - [Non-insulin-dependent diabetes: the B cell, victim or guilty party?].

PMID- 8760684
TI  - Treatment of mixed cryoglobulinemia with recombinant interferon alpha and
      adjuvant therapies. A prospective study on 20 patients.
AB  - In order to evaluate the efficacy of interferon alpha (IFNa) in mixed
      cryoglobulinemia (MC), a prospective multicenter clinical trial was conduced in
      April 1992. It consisted of treating 20 clinically symptomatic MC patients with
      IFNa for 26 weeks. Hepatitis C virus (HCV) infection was detected in 16 patients.
      A complete or partial clinical remission was obtained in 12 patients (60%).
      Eleven of these 12 responders (91.6%) experienced a clinical relapse less than 12
      months after the end of therapy. Side effects were noted in 10 patients (50%). It
      was concluded that subcutaneously administered IFNa does not provide long-term
      remission.

PMID- 8760685
TI  - [Physiopathology of non-insulin-dependent diabetes].

PMID- 8760686
TI  - [Ocular involvement in Basedow disease. Therapeutic strategy].

PMID- 8760687
TI  - [An interview with Bertrand Wechsler. What is going to happen in the field of
      Behcet disease?].

PMID- 8760688
TI  - [Digestive sites disclosing sarcoidosis].
AB  - We report two cases of gastrointestinal sarcoidosis. One patient had a gastric
      involvement, the other a duodenal and ileum involvement. The two patients had the
      same symptoms, including diarrhea, vomiting, abdominal pain and weight loss.
      Endoscopic examination revealed only an erythematous gastritis in the first
      patient, while the colon and the small bowel were macroscopically normal in the
      second. Histologic findings were consistent with a gastric and salivary gland
      sarcoidosis granulomata for the first patient and with a lung, duodenal and small
      intestine involvement for the second one. Gastrointestinal involvement in
      sarcoidosis is rare, especially small bowel localization. A brief discussion and
      a literature review of gastrointestinal sarcoidosis are presented.

PMID- 8760689
TI  - [Hypothermia and the nervous system. Review of the literature apropos of 4
      cases].
AB  - Thermoregulation involves a long term adaptation system with hormonal processes
      and an immediate regulation system by extrapyramidal tracts, sympathetic part of
      autonomic nervous system and cortical integration of body temperature changes.
      Both system are under control of a hypothalamic center. Prolonged accidental
      exposure to intense cold and myxoedematous coma are the best known etiologies of
      hypothermia. However milder and often misdiagnosed hypothermia can occur at home
      in patients without endocrinologic disease. In these cases, hypothermia is due to
      dysfunction of immediate thermregulation under neuronal control, especially
      somatomotor and autonomic system. We report four cases of hypothermia of this
      kind. Two patients had an inhibition of peripherical mechanisms of protecting
      against cold (cutaneous vasoconstriction, shivering) and had dampened perception
      of cold: one was 73, had diabetes mellitus and took different drugs, the other
      one suffered from systemic lupus with myelopathy. The two other patients probably
      had a disorder of the thermoregulation hypothalamic center: one had Wernicke's
      encephalopathy and the other multiple sclerosis. From these cases and a review of
      the literature, we describe the different etiologies of hypothermia and their
      pathophysiology.

PMID- 8760690
TI  - High frequency of C4 "null" alleles in primary antiphospholipid syndrome.

PMID- 8760691
TI  - [Therapeutic management of complicated ocular manifestations in Basedow disease].

PMID- 8760692
TI  - [Marchiafava-Bignami disease of favorable course].

PMID- 8760693
TI  - [Sarcoidosis pachymeningitis: value of meningeal biopsy].

PMID- 8760694
TI  - [Anaplastic cancer of the thyroid gland disclosed by prolonged fever or
      hyperleukocytosis. Two cases].

PMID- 8760695
TI  - [Myocardiopathy in POEMS syndrome].

PMID- 8760696
TI  - [Cardiac manifestations of Behcet disease. A propos of 3 cases].

PMID- 8760697
TI  - [Persistent parasitemia after treatment of Plasmodium falciparum flare-up in a
      non-immune patient with splenectomy].

PMID- 8760698
TI  - The active mismanagement of labour.

PMID- 8760699
TI  - Preserving the pelvic floor and perineum during childbirth--elective caesarean
      section?

PMID- 8760700
TI  - Guessing the weight of the baby.

PMID- 8760701
TI  - Direction, misdirection and misconception in menopause research and management.

PMID- 8760702
TI  - Clinical and ultrasound prediction of macrosomia in diabetic pregnancy.
AB  - OBJECTIVE: To study prospectively the prediction power, at different gestations,
      of clinical and ultrasound measurements for fetal size in diabetic pregnancy.
      SETTING: A large combined obstetric diabetic clinic in a teaching hospital.
      PARTICIPANTS: One hundred and eighty-one pregnancies in which women had scans at
      least two of three specific time points and who were delivered of singletons
      after 34 weeks: 73% were pre-gestational insulin-dependent diabetics, the others
      were pre-gestational White class A or gestational diabetics. INTERVENTIONS:
      Clinical estimates of fundal height and fetal size and ultrasound estimates of
      abdominal circumference and head circumference were routinely carried out at
      gestational ages of 28, 34 and 38 weeks or before delivery. MAIN OUTCOME
      MEASURES: Standardised birthweight, corrected for gestation and parity. The
      relation with clinical and ultrasound measurements was investigated using
      multiple linear regression and the capability of the measurements to predict
      macrosomic births (> 95th centile of normals) using receiver-operator
      characteristic curves. RESULTS: All measurements are poor predictors of eventual
      standardised birthweight. Prediction improves with closeness to delivery.
      Prediction is significantly improved by adding ultrasound to clinical
      information, but at 34 weeks or later this only contributes 8% of the variance.
      There is no difference in the prediction power for macrosomia between clinical
      and ultrasound measurements. CONCLUSIONS: Even regular serial scanning and
      clinical examination will not always diagnose the macrosomic fetus in diabetic
      pregnancy. In our hands, clinical examination is as predictive as ultrasound
      measurements. Ultrasound does add to clinical prediction power but only to a
      small extent. Ultrasound should be used in a selected way, as defined by clinical
      findings, and with recognition and understanding of the errors and biases
      involved.

PMID- 8760703
TI  - A randomised trial of two expectant managements of prelabour rupture of the
      membranes at 34 to 42 weeks.
AB  - OBJECTIVE: To compare obstetric and perinatal outcome between two different
      expectant managements in women with prelabour rupture of the membranes (PROM).
      DESIGN: A randomised study. PARTICIPANTS: One thousand three hundred and eighty
      five women with rupture of the membranes at 34 to 42 weeks without contractions.
      INTERVENTIONS: Women without contractions 2 h after admission were randomised to
      early induction the following morning after PROM (early induction group) or
      induction two days later (late induction group). Women with contractions starting
      within 2 h after admission were included in the calculations as a short latency
      group. Digital examinations of the cervix were avoided until onset of active
      labour. Labour was induced with oxytocin in both groups if no spontaneous
      contractions occurred or if chorioamnionitis or fetal distress was detected. MAIN
      OUTCOME MEASURES: The frequency of spontaneous deliveries, operative deliveries,
      maternal and neonatal infections. RESULTS: In nulliparous women, a higher rate of
      spontaneous deliveries was found in the late induction group (89%) compared with
      the early induction group (81%) (P < 0.05). The ventouse extraction rate was 7%
      and 14% respectively (P < 0.05). A low (2-4%) caesarean section rate was recorded
      and did not differ between the groups. Endometritis was detected in six women
      after delivery. Sixty-one children were treated with antibiotics, and no
      difference could be detected between the groups. CONCLUSIONS: A higher rate of
      spontaneous deliveries was found among nulliparous women with prolonged latency
      as compared with brief latency prior to induction. A protocol of no digital
      examination before labour was associated with infrequent maternal and fetal
      morbidity, regardless of latency.

PMID- 8760704
TI  - Head-to-cervix force: an important physiological variable in labour. 1. The
      temporal relation between head-to-cervix force and intrauterine pressure during
      labour.
AB  - OBJECTIVE: To investigate the relation between the rise in intrauterine pressure
      and rise in fetal head to cervix force in normal, slow and induced labour.
      DESIGN: Prospective observational study. SETTING: The labour ward of a London
      teaching hospital. PARTICIPANTS: Forty patients were recruited from the antenatal
      clinic and labour ward of a West London Hospital. Five had normal onset and
      progression of labour, 14 had slow progression of labour and 21 had induced onset
      of labour. METHOD: Intrauterine pressure and head-to-cervix force was measured
      simultaneously using an intrauterine pressure catheter and a specially designed
      four sensor head-to-cervix force probe. RESULTS: For each contraction of each
      labour, scattergrams of force by pressure were plotted. Three patterns were
      observed. When the rise in pressure preceded the rise in force, a positive 'loop'
      was generated. When the rise in pressure and force occurred simultaneously a
      linear pattern was generated (a neutral 'loop'). When the rise in pressure lags
      the rise in force, a negative 'loop' was generated. In normally progressive
      labour the distribution of loops was 29.1%, 22.6% and 48.3%, respectively, in
      slow labour the distribution was 26.1%, 14.1% and 59.8% and in induced labour the
      distribution was 33.8%, 14.4% and 51.8%. These distributions were not
      statistically different. However, a higher proportion of negative loops was
      observed in labours augmented with oxytocin compared to those receiving no
      oxytocin (MW-U = 87, P = 0.036). No differences were observed comparing parity,
      use of PGE2, epidural analgesia, or mode of delivery. Contraction frequency
      (number/10 minutes) was inversely correlated to the percentage of negative loops
      (rs = -0.34, P = 0.033) and positively correlated with percentage of positive
      loops (rs = 0.36, P = 0.027). CONCLUSIONS: This is the first report of the
      temporal relation between intrauterine pressure and head-to-cervix force in
      labour. The most common pattern is that the rise in pressure lags the rise in
      force, suggesting that a seal has to be created between the fetal head and cervix
      before a rise in pressure can occur. When oxytocin is given in labour, a higher
      proportion of loops are negative indicating that there is poor application of the
      fetal head and cervix in a greater proportion of contractions.

PMID- 8760705
TI  - Head-to-cervix force: an important physiological variable in labour. 2. Peak
      active force, peak active pressure and mode of delivery.
AB  - OBJECTIVE: To assess the relation between peak active (above baseline) head-to
      cervix force (paHCF) and peak active (above baseline) intrauterine pressure
      (paIUP) in labour, and to compare the relation between labours progressing well
      and ending in vaginal delivery and those labours progressing slowly and ending in
      caesarean section. DESIGN: Prospective observational study. SETTING: The labour
      ward of a London teaching hospital. PARTICIPANTS: Forty women in labour who
      agreed to have an experimental head-to-cervix force probe and an intrauterine
      pressure catheter inserted. RESULTS: The relation was linear, with a correlation
      coefficient which ranged from 0.012 to 0.885 (mean value 0.438). The closeness of
      the relation did not correlate with the rate of cervical dilatation (r = 0.0192,
      P = 0.574) or the mode of delivery (r = 0.215, P = 0.183). However, in women who
      progressed well to a vaginal delivery, the mean slope of the paHCF to paIUP
      regression line was 0.72, significantly steeper than in women who progressed
      slowly and required delivery by caesarean section (mean slope = 0.45, t = 2.31, P
      = 0.02). Mean paIUPs were significantly higher in women progressing well and
      achieving a vaginal delivery than in those progressing slowly and requiring
      caesarean section (45.3 mmHg SD 7.5 vs 38.4 mmHg SD 11.4, t = 2.31, P = 0.02),
      but the overlap between the two groups was considerable. However, in keeping with
      their steeper paHCF/paIUP slope, women progressing well to a vaginal delivery had
      substantially higher head-to-cervix forces (46.4 gWt SD 11.8 vs 28.3 gWt SD 8.2,
      t = 5.22, P < 0.00001) than those progressing slowly and requiring caesarean
      section, and there was much less overlap between paHCF than paIUP. This resulted
      in paHCF being a much better discriminating variable than paIUP for mode of
      delivery. CONCLUSIONS: The relation between paHCF and paIUP is linear, but there
      is a wide variation in the degree of correlation between one woman and another.
      Women with a steep slope of paHCF relative to paIUP are more likely to achieve a
      high mean paHCF, progress rapidly in labour and achieve a vaginal delivery than
      women with a flap slope, although mean paIUPs do not differ substantially between
      the two groups. The level of paHCF was substantially better than cervical
      dilatation rate at predicting mode of delivery. These results suggest that head
      to-cervix force is sensitive to factors determining mode of delivery which are
      not reflected in either the level of uterine activity as measured by intrauterine
      pressure, or cervical compliance as measured by cervical dilatation rates.

PMID- 8760706
TI  - The effect of maternal epidural analgesia on fetal oxygen saturation.
AB  - OBJECTIVE: To observe fetal arteriolar oxygen saturation during maternal epidural
      analgesia. DESIGN: An observation study of 27 epidural top-ups. SETTING: Labour
      ward, St James's University Hospital and Leeds General Infirmary, Leeds
      University, UK. SAMPLE: Seventeen fetuses in uncomplicated labour monitored with
      a N400 fetal pulse oximeter. OUTCOME MEASURE: A change in fetal pulse oximetry
      reading following epidural analgesia. RESULTS: There is no change in fetal oxygen
      saturation following an uncomplicated epidural top-up (F = 0.93; df 35 and 784).
      CONCLUSION: An uneventful maternal epidural has no measurable effect on fetal
      oxygen saturation measured with a N400 pulse oximeter.

PMID- 8760707
TI  - The relation between serum markers in the second trimester and placental
      pathology. A study on extremely small for gestational age fetuses.
AB  - OBJECTIVES: To examine whether in women who are delivered of an extremely small
      for gestational age infant, raised levels of second trimester maternal serum
      alpha-fetoprotein (MSAFP) or human chorionic gonadotrophin (MShCG) levels are
      related to the presence of placental pathology detected at birth. DESIGN:
      Retrospective cross-sectional study. SETTING: Department of Obstetrics and
      Gynaecology, Antenatal Diagnosis Unit, Groningen University Hospital, The
      Netherlands. PARTICIPANTS: Eighty-four women who were delivered of an extremely
      SGA infant (< 2.3rd centile) in whom the MSAFP and the MShCG levels were known
      and placental pathology reports were available (study group), and 8692 women in
      whom the MSAFP and MShCG levels were known and the pregnancy outcome was normal
      (control group). Pregnancies with congenital anomalies were excluded. Analyte
      levels were expressed in multiples of the median (MoM) for gestational age.
      Statistical analysis between groups was performed by ANOVA, after logarithmic
      transformation of the MoMs, to normalise their distribution. MAIN OUTCOME
      MEASURES: 1. The means of the MSAFP and MShCG concentrations in the study group
      with and without placental lesions were compared with those in the control
      population. 2. The means of the MSAFP and MShCG levels in the study group with
      placental lesions were compared with those in the study group without placental
      lesions. RESULTS: 1. Comparison of study groups with controls: in the study group
      without placental lesions, the mean log MSAFP MoM (0.062), as well as the mean
      log MShCG MoM (-0.033), was not significantly different (P = 0.11 and P = 0.68,
      respectively) from the mean analyte levels in the control population (0.002 and
      0.006, respectively). The mean logs of these analytes in the study group with
      placental lesions (0.162 and 0.129, respectively) were significantly higher
      compared with the MSAFP and MShCG levels in the control population (P < 0.001 for
      both analytes). 2. Comparison of study groups with each other: the mean log of
      the MSAFP level of 0.162 in the group with placental lesions was significantly
      different from the mean of 0.062 of the study group without placental lesions (P
      < 0.025). The higher mean log MShCG MoM of 0.129 in the group with placental
      lesions was significantly different from the mean log MShCG MoM of -0.033 in the
      study group without placental lesions (P < 0.025). CONCLUSIONS: Raised levels of
      second trimester MSAFP and MShCG in women who are subsequently delivered of an
      extremely small for gestational age infant are related to the presence of
      pathological changes in the placenta, detectable at birth. It is speculated that
      these placental pathological changes, which frequently accompany small for
      gestational age pregnancies, have their origin in the second trimester, when the
      normal physiological changes of the placenta occur.

PMID- 8760708
TI  - Obstetric outcome of pregnancies resulting from embryos biopsied for pre
      implantation diagnosis of inherited disease.
AB  - OBJECTIVE: Pre-implantation diagnosis of inherited disease is now a viable option
      for some couples at risk of transmitting inherited disorders to their children.
      Since the pregnancy begins knowing that the embryo is not at risk, the need for
      repeated terminations is eliminated. Up to 25% of the embryo is removed during
      the procedure, and so it is important to study the resulting pregnancies. Here we
      report on the obstetric outcome of our first 16 pregnancies resulting from embryo
      biopsy and preimplantation diagnosis of inherited disease. SETTING: Teaching
      hospital. SAMPLE: The first 16 pregnancies (12 singletons and 4 twins) following
      pre-implantation diagnosis. RESULTS: Three singleton pregnancies were lost in the
      first trimester. Of the remaining pregnancies, two had no prenatal diagnosis, six
      cases of X-linked disease had the sex confirmed by ultrasound and chorionic
      villus sampling was performed in the remaining five. All the singleton
      pregnancies had an uneventful antenatal course and the birthweights and Apgar
      scores of the babies were normal. The twin pregnancies presented obstetric
      complications but these were not unusual. CONCLUSIONS: Fifteen healthy infants
      were born, but for the foreseeable future pre-implantation diagnosis pregnancies
      should be closely followed up.

PMID- 8760709
TI  - Coagulation and fibrinolysis in smoking and nonsmoking pregnant women.
AB  - OBJECTIVES: To assess the effects of smoking during pregnancy on coagulation and
      fibrinolysis. DESIGN: A cross-sectional study. SETTING: A teaching hospital in
      Heerlen, The Netherlands. RESULTS: Parameters of coagulation activation increased
      significantly with gestational age. The values presented are median values.
      Prothrombin fragment 1 + 2 increased from 0.8 to 2.5 nmol/l in the nonsmoking
      group of pregnant women and from 1.0 to 1.8 nmol/l in the smoking group. Thrombin
      antithrombin III (TAT) levels increased from 2.2 to 9.9 micrograms/l in the
      nonsmoking group and from 3.1 to 8.5 micrograms/l in the smoking group.
      Parameters of fibrinolysis showed a different picture. Plasminogen levels in both
      groups rose significantly in the first half of gestation reaching a plateau in
      the second half. The alpha 2-antiplasmin levels remained constant in both groups,
      although the smokers started with significantly higher levels: 119 versus 105% in
      the nonsmokers. The D-dimer levels rose significantly in both groups: from 278 to
      847 micrograms/ml in the nonsmokers and from 215 to 520 micrograms/ml in the
      smokers. They were significantly lower in the smoking group from the 11th up to
      the 40th weeks. The D-dimer/TAT ratio was significantly higher in the nonsmokers.
      CONCLUSIONS: In smoking pregnant women the activated coagulation process was not
      counter balanced by an adequate increase of fibrinolysis which was the case in
      the nonsmokers.

PMID- 8760710
TI  - Antenatal screening for cystic fibrosis.
AB  - OBJECTIVE: To assess the practicality of implementing antenatal screening for
      cystic fibrosis in Yorkshire. DESIGN: Prospective study in which all pregnant
      women were offered testing for the delta F508 mutation which accounts for about
      85% of carriers in Yorkshire. The reproductive partners of those found to be
      cystic fibrosis carriers were then tested and any carrier referred for genetic
      counselling. SETTING: Antenatal clinics in two hospitals and eight general
      practices. POPULATION: Six thousand and seventy-one pregnant women. RESULTS: A
      total of 3773 women (62%) accepted the screening offer. This was a lower uptake
      rate than in other published UK studies: Aberdeen (85-91%), Manchester (85%),
      Edinburgh (76-84%) and Oxford (67%). Nonetheless there were large and
      statistically significant differences in the uptake rate between centres within
      the study: 78% and 60% for the two hospitals and 67% for the general practices.
      One hundred and thirty women (3.4%) were found to be carriers and three carrier
      couples were identified. The median time interval for the laboratory to produce a
      result was five days and the cost was pounds 16 on average. CONCLUSIONS:
      Antenatal screening for cystic fibrosis does not pose any special practical
      difficulties. It would be feasible to introduce it into routine practice in
      Yorkshire.

PMID- 8760711
TI  - Smoking during pregnancy and preterm birth.
AB  - OBJECTIVE: To evaluate the association between smoking during pregnancy and
      preterm birth. DESIGN: A follow up study. SETTING: Department of Gynaecology and
      Obstetrics, Aarhus University Hospital, Denmark. PARTICIPANTS: Four thousand one
      hundred and eleven nulliparous women with singleton pregnancies who returned
      questionnaires about smoking habits at 16 weeks of gestation. RESULTS: The
      overall rate of preterm delivery was 4.3%. Smokers had a 40% higher risk of
      preterm birth compared with nonsmokers. A dose response relationship was found
      between smoking and risk of preterm birth. Adjustment for women's height,
      prepregnancy weight, age of the mother, marital status, education, occupational
      status, and alcohol intake did not change the results. Among women with an intake
      of less than 400 mg of caffeine per day no difference in the risk of preterm
      birth between smokers and nonsmokers was found. However, among women with an
      intake of more than 400 mg of caffeine per day, the risk of preterm birth was
      increased almost threefold among smokers compared with nonsmokers. Furthermore,
      among women with a high intake of caffeine a dose-response relationship was
      found; women smoking one to five cigarettes per day had no increased risk of
      preterm birth compared with nonsmokers with the same intake of caffeine, women
      smoking six to ten cigarettes per day had almost three times higher risk of
      preterm birth, and women smoking more than 10 cigarettes per day had almost five
      times higher risk of preterm birth compared with nonsmokers with the same intake
      of caffeine. CONCLUSIONS: Smoking increases the risk of preterm birth. The
      association between smoking and preterm birth was only present among women with a
      high intake of caffeine. However, whether smoking alone influences the risk of
      preterm birth among heavy consumers of caffeine needs further investigation.

PMID- 8760712
TI  - Smoking during pregnancy: the dose dependence of birthweight deficits.
AB  - OBJECTIVE: To assess whether a simple urine based estimate of relative daily
      nicotine intake could predict smoking related birthweight deficits more
      accurately than self-reported cigarette consumption. DESIGN: Active smokers were
      identified by a simple qualitative colorimetric urine test procedure and their
      relative nicotine intakes assessed by determining the ratios of the urinary
      concentrations of nicotine plus its metabolites to creatinine using automated
      colorimetric methods. SETTING: A large teaching hospital. PARTICIPANTS: Three
      thousand and thirty-eight mothers from whom smoking histories had been elicited
      and who gave birth to live singleton babies after 28 weeks of gestation. MAIN
      OUTCOME MEASURES: Birthweights (adjusted for maternal weight, maternal age,
      baby's sex, parity and length of gestation), maternal weight gains during
      pregnancy and placental weights. RESULTS: The adjusted birthweight deficits of
      babies born to proven active smokers averaged 226 g (95% confidence interval 194
      g to 258 g), but dose dependent effects were only apparent when nicotine intake
      was based on urinary nicotine metabolites/creatinine ratios. Among the smokers,
      adjusted birthweights fell linearly with increasing nicotine intakes but gave a
      predicted mean birthweight for nonsmokers that was 102 g (95% CI 50 g to 154 g)
      lighter than that actually found (P < 0.0001). Maternal weight gains during
      pregnancy were substantially reduced in smokers and correlated more closely with
      urinary nicotine metabolite excretions than with reported daily cigarette
      consumptions. Placental weights were unaffected by smoking. CONCLUSION: There was
      a closer dose-effect relationship between birthweight deficits and urinary
      nicotine metabolites/creatinine ratios than with self-reported daily cigarette
      consumptions. The influence of nicotine exposure on birthweight appears to be
      biphasic, with one mechanism operating at very low levels of tobacco smoke intake
      and the other causing seemingly linearly related effects over the whole range of
      nicotine intakes of active smokers. These findings support recent evidence that
      passive smoking can cause substantial birthweight deficits.

PMID- 8760713
TI  - Childhood growth and age at menarche.
AB  - OBJECTIVE: To study the influence of birthweight, and weight and height at age
      seven years, on menarcheal age in a national sample of 1471 girls in England,
      Scotland and Wales. METHODS: We studied 1471 girls included in the MRC National
      Survey of Health and Development. During medical examinations carried out by
      school doctors in this cohort, born in the first week of March 1946, the mothers
      of girls were asked whether their daughters had started to menstruate, and if so,
      the month and year when this happened. Anthropometric measurements at birth and
      at age seven years were also obtained. RESULTS: Girls who were heavier at age
      seven years had menarche at an earlier age. The average age at menarche of those
      in the highest fifth of the distribution of weight at seven years was 7.3 months
      less than that of those in the lowest fifth of the distribution. In contrast,
      girls who were heavier at birth had menarche at a later age. The average age at
      menarche of those in the highest fifth of the birthweight distribution was 2.2
      months more than those in the lowest fifth. These opposing trends of birthweight
      and weight at seven years on age at menarche were observed across the
      distribution of each variable, and exerted statistically significant (P < 0.001)
      independent effects in a multivariate model. CONCLUSIONS: These observations are
      consistent with the hypothesis that menarcheal age is linked to programmed
      patterns of gonadotrophin release established in utero, when the fetal
      hypothalamus is imprinted, and is subsequently modified by weight gain in
      childhood.

PMID- 8760714
TI  - Multiparity and bone mass.
AB  - OBJECTIVE: To investigate the influence of multiparity on bone mass of the axial
      skeleton in a population of women of high parity. DESIGN: Open study of Omani
      women. SETTING: Medical physics department and clinical physiology department of
      a third degree referral (university) hospital. PARTICIPANTS: A consecutive series
      of 159 normal women referred with low back pain over a period of six months.
      RESULTS: The bone mineral density was measured with dual-photon absorptiometry
      and the mean was found to be 0.984 (+/-0.166) (+/- SD) g cm-2. The age ranged
      from 20 to 70 years with a mean age of 43.4 (+/- 12.5) years. The number of
      children per woman ranged from 0 to 14 with a mean of 5.1 (+/- 3.5). There was no
      statistically significant influence of the number of children per woman on bone
      mineral density but there was a strong correlation with age and body size
      variables. CONCLUSION: Multiparity does not influence lumbar spine bone mineral
      density in normal women.

PMID- 8760715
TI  - Wedge resection to improve insulin resistance in polycystic ovary syndrome: a
      study among Chinese women.
AB  - OBJECTIVE: To investigate the relation between androgen excess and insulin
      resistance in nonobese Chinese women with polycystic ovary syndrome. DESIGN: A
      prospective, controlled study. SETTING: School of Clinical Medicine, Nanjing
      University. SUBJECTS: There were three groups: Group 1 (n = 15) comprised
      nonobese women with polycystic ovary syndrome; Group 2 comprised 12 of these 15
      women in whom bilateral wedge resection had been performed six months to one year
      before enrolling in the study. Group 3 was a control group comprised of 15
      normally menstruating women of similar age and body mass index. METHODS: An oral
      glucose (100 g) tolerance test was performed in all women in each group. The
      areas under the response curve of serum glucose, insulin, C-peptide (C-P),
      insulin/glucose (I/G) and C-P/insulin (C/I) were calculated by trapezoid rule.
      RESULTS: When fasting the three groups had similar levels of glucose, insulin, C
      P, I/G and C/I. During the oral glucose tolerance test women of Group 1 had a
      significantly higher mean serum area of the curve of glucose, insulin, C-P and
      I/G levels and lower C/I values, compared with the other two groups. Women of
      Group 2 and those in the control group showed similar levels of these indices
      during the oral glucose tolerance test. CONCLUSIONS: Androgen excess in women
      with polycystic ovary syndrome may be responsible for a defect in peripheral
      insulin sensitivity and hepatic extraction which could be reversed by removing
      excessive androgens with wedge resection.

PMID- 8760716
TI  - Evaluation of a risk of malignancy index based on serum CA125, ultrasound
      findings and menopausal status in the pre-operative diagnosis of pelvic masses.
AB  - OBJECTIVE: To evaluate the ability of a risk of malignancy index (RMI), based on
      a serum CA125 level, ultrasound findings and menopausal status, to discriminate a
      benign from a malignant pelvic mass and to discriminate early stage (Figo Stage
      I) from Stages II, III and IV of ovarian cancer. DESIGN: A prospective study.
      SETTING: Department of Gynaecology, Trondheim University Hospital, Trondheim,
      Norway. PARTICIPANTS: One hundred and seventy-three women, 30 years or older,
      consecutively admitted between February 1992 and February 1994 for primary
      laparotomy of a pelvic mass. MAIN OUTCOME MEASURES: The sensitivity, specificity
      and positive predictive value of serum CA125 level, ultrasound findings and
      menopausal status, separately and combined into the RMI, to diagnose ovarian
      cancer. RESULTS: The RMI was more accurate than any individual criterion in
      diagnosing cancer. Using a RMI cut-off level of 200 to indicate malignancy, the
      RMI derived from this dataset gave a sensitivity of 80%, specificity of 92% and
      positive predictive value of 83%. Applying RMI criteria developed by others, the
      following test performance was found: sensitivity 71%, specificity 96% and
      positive predictive value 89%. For the Stages II, III and IV of ovarian cancer
      the sensitivity increased to approximately 90% without any substantial loss in
      specificity. CONCLUSIONS: The risk of malignancy index is able to correctly
      discriminate between malignant and benign pelvic masses. It is a scoring system
      which can be introduced easily into clinical practice to facilitate the selection
      of patients for primary surgery at an oncological unit.

PMID- 8760717
TI  - Neurological symptoms attributed to epidural analgesia in labour: an
      observational study of seven cases.

PMID- 8760718
TI  - Low cyclic guanosine monophosphate levels in the amniotic fluid of pre-eclamptic
      pregnancies.

PMID- 8760719
TI  - An assessment of the value of intraperitoneal bupivacaine for analgesia after
      laparoscopic sterilisation.

PMID- 8760720
TI  - Diagnosis of myometrial invasion of endometrial cancer by intrauterine
      ultrasonography with a high-frequency probe and fluid contrast augmentation in
      the uterine cavity: a preliminary study.

PMID- 8760721
TI  - Placental thrombosis and second trimester miscarriage in association with
      activated protein C resistance.

PMID- 8760722
TI  - Impaired implantation after in vitro fertilisation treatment associated with
      hydrosalpinx.

PMID- 8760723
TI  - A comprehensive one-stop menstrual problem clinic for the diagnosis and
      management of abnormal uterine bleeding.

PMID- 8760724
TI  - Longitudinal study of fetal middle cerebral artery flow velocity waveforms
      preceding fetal death.

PMID- 8760725
TI  - Magnesium sulphate: the time for reckoning.

PMID- 8760726
TI  - Augmentation of trypsin resistance of retinal pigment epithelium adhesion in
      vitro by near ultraviolet.
AB  - In the process of subculturing near-ultraviolet (NUV)-irradiated retinal pigment
      epithelial (RPE) monolayers by trypsinization, we surprisingly found that the
      adhesion capacity of these cells was significantly enhanced. The nature of the
      enhanced cell adhesion induced by NUV was then studied. To quantitate this
      capacity, RPE monolayers were exposed to 0.05% trypsin in the presence of 0.53 mM
      EDTA for 10 min at 37 degrees C. The ratio of RPE cells remaining on the culture
      surface over total cells was measured and termed as trypsin resistance. (TR). TR
      of RPE cells without NUV irradiation was null (TR = 0). With NUV energy at 3.24
      or 12.96 J/cm2, the RPE-TR was increased to 56.8 +/- 8.5 or 82.3 +/- 8.8%,
      respectively. With NUV irradiation above 12.96 J/cm2, TR reached a plateau,
      suggesting a maximal inducible adhesion capacity. When RPE cells were irradiated
      in an oxygen-free environment, TR was 33.5 +/- 1.6% lower than that in an oxygen
      saturated condition, suggesting that it is an oxygen-related process. NUV
      enhanced TR was inversely correlated with the concentration of trypsin or the
      trypsin digestion time. Moreover, NUV-induced TR was gradually diminished with
      elapsed time. The pre-exposed NUV energy inversely determined the degree of TR
      recovery. Cycloheximide, a protein synthesis inhibitor, prevented the recovery of
      TR. These results suggest that NUV-induced TR is a NUV-energy-dependent process.
      The new protein(s) which is required for TR recovery needs to be further
      identified.

PMID- 8760727
TI  - Telling patients there is nothing wrong.

PMID- 8760728
TI  - Private finance for the public good?

PMID- 8760729
TI  - Choosing tomorrow's doctors.

PMID- 8760730
TI  - Growth hormone deficiency and replacement in adults.

PMID- 8760731
TI  - Informing patients about the drugs they take.

PMID- 8760733
TI  - Scientists find low level transmission of BSE.

PMID- 8760732
TI  - Health for all by the year 2000?

PMID- 8760734
TI  - Violence may be predicted among psychiatric patients.

PMID- 8760735
TI  - Combination drug treatment benefits patients with HIV.

PMID- 8760737
TI  - Analgesic efficacy and safety of paracetamol-codeine combinations versus
      paracetamol alone: a systematic review.
AB  - OBJECTIVES: To assess whether adding codeine to paracetamol has an additive
      analgesic effect; to assess the safety of paracetamol-codeine combinations versus
      paracetamol alone. DESIGN: Systematic literature review with meta-analysis,
      methodological quality of published trials being scored by means of 13 predefined
      criteria. TRIALS: 24 of 29 trials that met the inclusion criteria. Models studied
      in the trials were postsurgical pain (21), postpartum pain (one), osteoarthritic
      pain (one), and experimentally induced pain (one). INTERVENTIONS: Dosages ranged
      from 400 to 1000 mg paracetamol and 10 to 60 mg codeine. MAIN OUTCOME MEASURES:
      The sum pain intensity difference (efficacy analysis) and the proportion of
      patients reporting a side effect (safety analysis). RESULTS: Most trials were
      considered of good to very good quality. Only the single dose studies could be
      combined for analysis of analgesic efficacy. Pooled efficacy results indicated
      that codeine added to paracetamol provided a 5% increase in analgesia on the sum
      pain intensity difference. This effect was comparable to the difference in
      analgesic effect between codeine and placebo. The cumulative incidence of side
      effects with each treatment was comparable in the single dose trials. In the
      multidose studies a significantly higher proportion of side effects occurred with
      paracetamol-codeine preparations. CONCLUSION: The difference is analgesic effect
      between paracetamol-codeine combinations and paracetamol alone was small but
      statistically significant. In the multidose studies the proportion of patients
      reporting a side effect was significantly higher with paracetamol-codeine
      combinations. For occasional pain relief a paracetamol-codeine combination might
      be appropriate but repeated use increases the occurrence of side effects.

PMID- 8760738
TI  - Randomised, double blind, placebo controlled trial of penicillin V and
      amoxycillin in treatment of acute sinus infections in adults.
AB  - OBJECTIVES: To compare the effectiveness of penicillin V and amoxycillin with
      placebo in treatment of adult patients with acute sinusitis. DESIGN: Randomised,
      double blind, placebo controlled trial. SETTING: Norwegian general practice.
      SUBJECTS: 130 adult patients with a clinical diagnosis of acute sinusitis
      confirmed by computed tomography. MAIN OUTCOME MEASURES: Subjective status after
      three and 10 days of treatment, difference in clinical severity score between day
      0 and day 10 as evaluated by the general practitioner, difference in score from
      computed tomography on day 0 and day 10, and duration of sinusitis. RESULTS:
      Amoxycillin and penicillin V led to significantly faster and better recovery than
      placebo. By day 10, 71 patients receiving antibiotic treatment- (86%) considered
      themselves to be recovered or much better compared with 25 (57%) receiving
      placebo. The mean (95% confidence interval) reductions in clinical severity
      scores by day 10 were 5.4 (5.0 to 5.8) for penicillin V, 5.5 (4.9 to 6.0 for
      amoxycillin, and 3.4 (2.8 to 4.0) for placebo. For the antibiotic groups combined
      the number of patients with the greatest degree of improvement on computed
      tomography (scale 0-16)-that is, score 5-16 on day 10-was 31/83 (37%) compared
      with 10/44 (23%) receiving placebo. The median duration of the sinusitis was nine
      days in the amoxycillin group, 11 days in the penicillin V group, and 17 days in
      the placebo group. CONCLUSION: Penicillin V and amoxycillin are significantly
      more effective than placebo in the treatment of acute sinusitis.

PMID- 8760739
TI  - Opening Pandora's box: the unpredictability of reassurance by a normal test
      result.
AB  - OBJECTIVES: To determine the rate of failure of patient reassurance after a
      normal test result and study the determinants of failure. DESIGN: Replicated
      single case study with qualitative and quantitative data analysis. SETTING:
      University teaching hospital. SUBJECTS: 40 consecutive patients referred for
      echocardiography either because of symptoms (10 patients) or because of a heart
      murmur (30). 39 were shown to have a normal heart. INTERVENTIONS: Medical
      consultations and semistructured patient interviews were tape recorded.
      Structured interviews with consultant cardiologists were recorded in survey form.
      MAIN OUTCOME MEASURES: Patient recall of the explanation and residual
      understanding, doubt, and anxiety about the heart after the test and post-test
      consultation. RESULTS: All 10 patients presenting with symptoms were left with
      anxiety about the heart despite a normal test result and reassurance by the
      consultant. Of 28 patients referred because of a murmur but shown to have no
      heart abnormality, 20 became anxious after detection of the murmur; 11 had
      residual anxiety despite the normal test result. CONCLUSIONS: Reassurance of the
      "worried well"-anxious patients with symptoms or patients concerned by a health
      query resulting from a routine medical examination or from screening-constitutes
      a large part of medical practice. It seems to be widely assumed that explaining
      that tests have shown no abnormality is enough to reassure. The results of this
      study refute this and emphasise the importance of personal and social factors as
      obstacles to reassurance.

PMID- 8760740
TI  - Serum complex of trypsin 2 and alpha 1 antitrypsin as diagnostic and prognostic
      marker of acute pancreatitis: clinical study in consecutive patients.
AB  - OBJECTIVE: To estimate the usefulness of serum concentrations of the complex of
      trypsin 2 and alpha 1 antitrypsin in diagnosing and assessing the severity of
      acute pancreatitis in comparison with serum C reactive protein, amylase, and
      trypsinogen 2 concentrations (reference markers). DESIGN: Markers were measured
      in consecutive patients admitted with acute abdominal pain that was either due to
      pancreatitis or to other disease unrelated to the pancreas (controls). SETTING:
      Department of surgery of a teaching hospital in Helsinki. SUBJECTS: 110 patients
      with acute pancreatitis and 66 with acute abdominal diseases of extrapancreatic
      origin. On the basis of the clinical course, acute pancreatitis was classified as
      mild (82 patients) or severe (28 patients). MAIN OUTCOME MEASURES: Clinical
      diagnosis of acute pancreatitis and severity of the disease. RESULTS: At
      admission all patients with acute pancreatitis had clearly raised concentrations
      of trypsin 2-alpha 1 antitrypsin complex (32 micrograms/l), whereas only three of
      the controls had such values. Of the markers studied, trypsin 2-alpha 1
      antitrypsin complex had the largest area under the receiver operating curve, both
      in differentiating acute pancreatitis from extrapancreatic disease and in
      differentiating mild from severe disease. CONCLUSIONS: Of the markers studied,
      trypsin 2-alpha 1 antitrypsin complex was the most accurate in differentiating
      between acute pancreatitis and extrapancreatic disease and in predicting a severe
      course for acute pancreatitis.

PMID- 8760741
TI  - Perinatal characteristics in relation to incidence of and mortality from prostate
      cancer.
AB  - OBJECTIVE: To test the hypothesis that factors causing morbidity and mortality
      from prostate cancer may operate in utero. DESIGN: Matched case-control study of
      singleton men born between 1874 and 1946 at one hospital. SETTING: Uppsala
      University Hospital. SUBJECTS: 250 patients with prostate cancer and 691
      controls, including 80 patients who died from prostate cancer and their 196
      matched controls. MAIN OUTCOME MEASURES: Mother's age at menarche, parity, pre
      eclampsia or eclampsia before delivery, age at delivery and socioeconomic status;
      case or control's birth length and weight, placental weight, prematurity derived
      from gestational age, and presence of jaundice. RESULTS: Both pre-eclampsia (odds
      ratio 0, 95% confidence interval 0 to 0.71) and prematurity (0.31, 0.09 to 1.04)
      were inversely associated with incidence of prostate cancer. Among subjects born
      full term, placental weight, birth weight, and ponderal index (weight/height 3)
      showed non-significant positive associations with prostate cancer incidence, and
      stronger associations with mortality. CONCLUSION: Prenatal exposures that are
      likely correlates of pregnancy hormones and other growth factors are important in
      prostate carcinogenesis and influence the natural course as well as the
      occurrence of this cancer.

PMID- 8760742
TI  - Fluctuations of HIV load in semen of HIV positive patients with newly acquired
      sexually transmitted diseases.

PMID- 8760743
TI  - Use of the capture-recapture technique to evaluate the completeness of systematic
      literature searches.

PMID- 8760744
TI  - Iron deficiency anaemia and febrile convulsions: case-control study in children
      under 2 years.

PMID- 8760745
TI  - Use of oral corticosteroids in the community and the prevention of secondary
      osteoporosis: a cross sectional study.
AB  - OBJECTIVE: To determine the prevalence of continuous use of oral steroids in the
      general population, the conditions for which they are prescribed, and the extent
      to which patients taking oral steroids are taking treatment to prevent
      osteoporosis. DESIGN: A cross sectional study with a four year retrospective
      review of drug treatment. SETTING: Eight large general practices in central and
      southern Nottinghamshire. SUBJECTS: A population of 65,786 patients (52% women)
      registered with a general practitioner during 1995. RESULTS: 303 patients (65%
      (197) women) aged 12-94 years were currently taking "continuous" (for at least
      three months) oral corticosteroid treatment. This figure represents 0.5% of the
      total population and 1.4% (245/17 114) of patients aged 55 years or more (1.7%
      (166/9601) of women). The usual steroid was prednisolone (97% (294/303)), the
      mean dose was 8.0 mg/day, and the median duration of oral steroid treatment
      determined in 149 patients was three years. The most common conditions for which
      continuous oral steroids were prescribed were rheumatoid arthritis (23% (70)),
      polymyalgia rheumatica (22% (66)), and asthma or chronic obstructive airways
      disease (19% (59)). Only 41 (14%) of the 303 patients taking oral steroids had
      received treatment for the prevention of osteoporosis over the past four years.
      Although 37 of the 41 patients were women, only 10% (18/181) of the women over 45
      years taking continuous oral corticosteroids were currently taking hormone
      replacement therapy. CONCLUSIONS: If our figures are typical then they suggest
      that over 250,000 people in the United Kingdom are taking continuous oral
      steroids and that most of these are taking no prophylaxis against osteoporosis.

PMID- 8760746
TI  - Tertiary cancer services in Britain: benchmarking study of activity and
      facilities at 12 specialist centres.
AB  - OBJECTIVE: To collate information on current activity and facilities in British
      hospitals to assist the planning of future cancer services. DESIGN: 12 hospitals
      delivering specialist cancer services provided information on the size of
      population served, activity levels related to non-surgical oncology for 1994-5,
      and facilities available. Inconsistencies in the recording of data were resolved
      through meetings of all participants. SETTING: Five single specialty NHS trusts
      and seven specialist cancer facilities within multispecialty trusts, serving a
      combined population of 24.3 million. MAIN OUTCOME MEASURES: Activity levels and
      facilities per million population served. RESULTS: The facilities available per
      million population served varied widely between centres. In contrast, the range
      in the number of new referrals per million population (seen either at the centre
      or in peripheral clinics) was relatively small. Considerable variations were
      observed in the number of attendances per patient and amount of radiotherapy and
      chemotherapy delivered. Overall it was estimated that 40-45% of all new cases of
      cancer are currently being referred to non-surgical oncologists. For the seven
      hospitals which could provide data on trends in activity, the average increase in
      chemotherapy day case episodes between 1992-3 and 1994-5 was 83%. CONCLUSIONS:
      The results of this study provide a benchmark both for purchasers and providers
      of cancer care. The increase in the use of chemotherapy points to an urgent need
      for a unified system for monitoring both activity and outcomes of treatment.

PMID- 8760747
TI  - Hormone replacement therapy for all? Universal prescription is desirable.

PMID- 8760748
TI  - Hormone replacement therapy for all? Not for everybody.

PMID- 8760749
TI  - Caring for older people. Loneliness.

PMID- 8760750
TI  - ABC of work related disorders. Back pain.

PMID- 8760751
TI  - Proposal to abolish resale price maintenance on medicines. Resale price
      maintenance must continue.

PMID- 8760752
TI  - Psychological support for patients having breast cancer surgery. Study had
      methodological flaws.

PMID- 8760753
TI  - Psychological support for patients having breast cancer surgery. Support groups
      whose members have themselves had breast cancer are helpful.

PMID- 8760754
TI  - Psychological support for patients having breast cancer surgery. Patients'
      consent should have been sought.

PMID- 8760755
TI  - Psychological support for patients having breast cancer surgery. Data may not
      have been summarised appropriately.

PMID- 8760756
TI  - Gaining patients' consent. Description of orthopaedic operations is inaccurate in
      half of consent forms.

PMID- 8760757
TI  - Gaining patients' consent. Telling parents all relevant details might reduce
      recruitment of children to trials.

PMID- 8760758
TI  - Effect of CSM's warning about safety of third generation oral contraceptive.
      General practitioners in England prescribed second generation pills instead.

PMID- 8760759
TI  - Effect of CSM's warning about safety of third generation oral contraceptives.
      Contraceptive effectiveness may be being sacrificed for safety.

PMID- 8760760
TI  - Effect of CSM's warning about safety of third generation oral contraceptives.
      Abortions increased by nearly 8% in Norway.

PMID- 8760761
TI  - Depression in carers of elderly people living at home.

PMID- 8760762
TI  - Transdermal glyceryl trinitrate for dysmenorrhoea. Confidence intervals for
      glyceryl trinitrate do not suggest a significant effect.

PMID- 8760763
TI  - Contamination of ampicillin was probably due to reuse of disposable stoppers.

PMID- 8760764
TI  - Alcohol consumption and risk of coronary heart disease. Studies suggest that wine
      has additional effect to that of ethanol.

PMID- 8760765
TI  - Alcohol consumption and risk of coronary heart disease. Association cannot be
      assumed to be causal.

PMID- 8760766
TI  - Review of interventions should help to reduce inequalities in health.

PMID- 8760767
TI  - Time for a ban on landmines. Workload resulting from landmine injuries is huge
      burden on hospitals.

PMID- 8760768
TI  - Time for a ban on landmines. Doctors should actively support campaign to ban
      landmines.

PMID- 8760769
TI  - GPs' prescribing behaviour may be affected by drug promotion.

PMID- 8760770
TI  - Junior Doctors Committee has achieved much recently.

PMID- 8760772
TI  - The continuing saga of imported fire ants: evolution before our eyes.

PMID- 8760773
TI  - Hypersensitivity to fire ant venom.
AB  - LEARNING OBJECTIVES: Reading this article will reinforce the reader's knowledge
      of the taxonomy, origin, and distribution of fire ants and will increase his
      ability to diagnose and manage reactions caused by the two imported species,
      Solenopsis invicta and richteri. This review will also enhance the reader's
      knowledge of the available diagnostic methods and therapeutic measures, including
      the role of fire ant venom versus whole body extract in the management of fire
      ant allergy. DATA SOURCES: Information for this review was obtained primarily
      from abstracts and articles written by investigators recognized for their
      expertise in fire ant venom research. STUDY SELECTION: References were selected
      based on their clinical applicability and relevance to the epidemiology and
      pathophysiology of imported fire ant hypersensitivity. CONCLUSIONS: The imported
      fire ant represents a significant health hazard for persons living in fire ant
      endemic areas in the southern United States. Sting reactions range from local
      pustules and large, late-phase responses to life-threatening anaphylaxis. Fire
      ant allergen-specific immunotherapy can reduce the risk of subsequent systemic
      reactions. Four important Sol i venom allergens have been isolated and
      characterized. Clinical studies have been designed to compare the safety and
      efficacy of fire ant venom with whole body extract for diagnosis and treatment of
      fire ant allergy.

PMID- 8760774
TI  - Acute severe urticaria and angioedema leading to myocardial infarction.

PMID- 8760775
TI  - Controlled-release theophylline inhibits early morning airway obstruction and
      hyperresponsiveness in asthmatic subjects.
AB  - BACKGROUND: Nocturnal asthma reflects the severity of the disease, and thus its
      pharmacologic prevention represents one on the main goals of asthma management.
      SUBJECTS AND METHODS: To determine whether controlled-release theophylline
      inhibits the development of airway obstruction and/or airway hyperresponsiveness
      early in the morning, we examined 18 subjects reporting recurrent nocturnal
      asthma. In each subject, after five days' treatment with an 8 PM increasing dose
      of oral controlled-release theophylline, up to 10 +/- 1 mg/kg or placebo the
      night before the study day, we measured serum theophylline, FEV1 and PC20FEV1 at
      6 AM, 2 PM and 10 PM. RESULTS: At 6 AM, both FEV1 and PC20FEV1 were significantly
      higher on theophylline than on placebo (3.52 +/- 0.22 versus 3.17 +/- 0.25 L; P <
      .005 and 2.76 divided by 3.61 versus 1.55 divided by 3.73 mg/mL; P < .05,
      respectively). At 2 PM and 10 PM FEV1, but not PC20FEV1, was higher on
      theophylline than on placebo (3.73 +/- 0.21 versus 3.54 +/- 0.25 L; P < .05 and
      3.40 +/- 0.22 versus 3.24 +/- 0.24 L; P < .05). Serum theophylline was 12.8 +/-
      1.1 micrograms/ml, 8.9 +/- 0.77 and 9.5 +/- 0.85 at 6 AM, 2 PM and 10 PM,
      respectively. CONCLUSIONS: We conclude that an evening dose of controlled-release
      theophyl line inhibits early morning airway obstruction and hyperresponsiveness,
      and that it may be helpful in the prevention of nocturnal asthma.

PMID- 8760776
TI  - Fluticasone propionate compared with theophylline for mild-to-moderate asthma.
AB  - BACKGROUND: The inhaled corticosteroid, fluticasone propionate, was compared with
      the oral bronchodilator theophylline in the maintenance treatment of asthma.
      OBJECTIVE: The objective of the present study was to compare the efficacy and
      safety of twice-daily inhaled fluticasone propionate, 50 micrograms, and
      fluticasone propionate, 100 micrograms, with that of theophylline in the
      maintenance treatment of mild-to-moderate asthma. METHODS: In this randomized,
      double-blind, placebo-controlled, parallel-group study, 353 adult and adolescent
      patients with asthma inadequately controlled with inhaled beta-agonist therapy
      alone received fluticasone propionate, 50 micrograms, or fluticasone propionate,
      100 micrograms, by metered-dose inhaler; theophylline capsules; or placebo twice
      daily for 12 weeks. Only inhaled albuterol was permitted as needed for acute
      symptoms. RESULTS: Both fluticasone propionate groups had a significantly greater
      probability of remaining in the study (ie, meeting asthma stability criteria)
      than did either the theophylline or placebo group (P < or = .008); 39% and 51% in
      the theophylline and placebo groups, respectively, were withdrawn due to lack of
      treatment efficacy compared with 14% and 21% in the fluticasone propionate, 50
      micrograms, and fluticasone propionate, 100 micrograms, groups. Both fluticasone
      propionate groups experienced significantly greater improvement in FEV1 and PEF
      compared with patients in the theophylline or placebo group (P < or = .004). The
      incidence of potentially drug-related adverse events was significantly greater in
      the theophylline group (25%) than in the placebo group (11%) (P = .031), while
      there were no differences between placebo and fluticasone propionate, 50
      micrograms, (18%) or fluticasone propionate 100 micrograms, (22%). CONCLUSION:
      Twice daily treatment with inhaled fluticasone propionate 50 micrograms or 100
      micrograms was significantly more effective than theophylline in the treatment of
      mild-to-moderate asthma.

PMID- 8760777
TI  - Peripheral blood eosinophilia, hyperimmunoglobulinemia A and fatigue: possible
      complications following rupture of silicone breast implants.
AB  - BACKGROUND: Silicone breast implantation has been considered quite safe and of
      major cosmetic value. Immunologic sequelae such as collagen vascular diseases
      have not been confirmed in large studies. OBJECTIVE: We describe a 55-year-old
      woman who developed severe fatigue, peripheral blood eosinophilia, and
      hyperimmunoglobulinemia A after rupture of a silicone breast implant during
      closed manual manipulation to lyse fibrotic tissue. METHODS: We charted evidence
      for eosinophilia over a 19-year period and determined quantitative
      immunoglobulins, and lymphocyte subsets by FACS analysis. RESULTS: Peripheral
      eosinophilia in 1976 was 693/mm3 and increased to 1360/mm3 after rupture of the
      implant in 1992. Serum immunoglobulin A was 332 mg/dL in 1976 and ranged after
      rupture from 473 to 627 mg/dL without other cause. Fatigue was not reversed with
      a parenteral corticosteroid injection. CD4 and CD8 subsets were normal but 40% of
      CD3 cells were Ia positive although not CD25 positive (IL2 receptor). Only 5% of
      B cells were CD19 CD23 positive despite the high concentration of serum IgA.
      CONCLUSION: This case is an example of a previously unreported apparent adverse
      effect of silicone-breast implant rupture with persisting eosinophilia,
      hyperimmunoglobulinemia A, and fatigue.

PMID- 8760778
TI  - Efficacy of nedocromil sodium and cromolyn sodium in an experimental model of
      ocular allergy.
AB  - BACKGROUND: Because ocular allergic disorders are important in terms of frequency
      and severity, there is a constant search for new topical antiallergic drugs.
      Nedocromil sodium has recently been introduced as a potential substitute for the
      mast cell stabilizer cromolyn sodium. OBJECTIVE: We compared the efficacy of
      topical 2% nedocromil sodium to that of 2% cromolyn sodium in treatment of the
      early-phase reaction of an experimental model of allergic conjunctivitis.
      METHODS: Guinea pigs were challenged topically with egg albumin 14 days after
      systemic immunization. Fifteen minutes before, immediately prior to, and 15
      minutes after topical challenge, the animals received either 2% nedocromil sodium
      or 2% cromolyn sodium topically in one eye and phosphate buffered saline (PBS) in
      the other eye. Antigen-induced increase in vascular permeability was measured by
      the extravasation of intravenously injected Evans blue dye. Animals that were
      immunized and topically challenged but did not receive Evans blue were used for
      histologic studies. RESULTS: Evans blue extravasation from ocular tissues
      significantly decreased in drug-treated eyes compared with PBS-treated eyes (P <
      .01). Further, the cellular infiltrate (mast cells, eosinophils, and neutrophils)
      in the substantia propria of the conjunctiva was markedly reduced in the drug
      treated eyes. No significant difference was observed between the nedocromil
      sodium- or cromolyn sodium-treated eyes. CONCLUSIONS: Topical 2% nedocromil
      sodium reduces the early-phase reaction of the allergic response as effectively
      as 2% sodium cromoglycate in a guinea pig model of ocular anaphylaxis.

PMID- 8760779
TI  - Immunologic effects of encapsulated short ragweed extract: a potent new agent for
      oral immunotherapy.
AB  - BACKGROUND: Oral allergen immunotherapy with conventional allergens has not been
      a useful mode of treatment because of the lack of potency of allergens when
      administered by this route. OBJECTIVE: To study the immunologic potency of short
      ragweed pollen extracts microencapsulated by a new technique administered orally
      to short ragweed pollen-sensitive humans and to establish the dose of oral
      microencapsulated short ragweed pollen extract required for these effects.
      METHODS: Nine short ragweed pollen-sensitive patients were treated with a new
      oral agent for immunotherapy, microencapsulated short ragweed pollen extract, in
      an open study. The effectiveness of this treatment was determined by comparison
      to a group of nine matched short ragweed pollen-sensitive patients who received
      no treatment. Treated patients developed high titers of short ragweed-specific
      IgG and IgE antibodies and their expected seasonal increase in IgE antibodies was
      regulated. The dose of microencapsulated short ragweed pollen extract required to
      achieve these effects was only slightly higher than the dose of short ragweed
      pollen extract used in high dose subcutaneous immunotherapy. Furthermore, this
      dose was achieved in 7 weeks. There were no side effects other than mild
      gastrointestinal ones. The nine treated patients fared clinically better during
      the ragweed season than the untreated patients in this open study. CONCLUSION:
      This study suggests that allergens microencapsulated by this new technique may
      make oral immunotherapy a practical mode of treatment.

PMID- 8760780
TI  - Effects of in vitro mast cell degranulation on human lung beta-receptor binding
      parameters.
AB  - BACKGROUND: Numerous studies have demonstrated that subjects with allergic asthma
      have beta-adrenergic hyporesponsiveness, predisposing these individuals toward
      bronchospasm, mucous production, and mast cell degranulation. Since sympathetic
      innervation of the human respiratory tract is sparse, reduced beta-responsiveness
      probably results from alterations at or beyond the receptor level. OBJECTIVE: We
      therefore examined whether anaphylaxis of human lung tissue acutely modulated the
      human lung beta-receptor system in ways that might lead to decreased beta
      adrenergic responsiveness. METHODS: Fresh thoracotomy peripheral lung samples
      from 26 patients were incubated with (anaphylaxis) or without (control) anti-IgE
      (1:100) for up to 90 minutes and histamine release was documented. Lung fragments
      were quick frozen at various times after anti-IgE for analyses of beta-receptor
      binding parameters. Antagonist Kd (dissociation constant) and receptor
      concentration values were determined using (-)[125I]pindolol and agonist IC50
      values were determined using isoproterenol. RESULTS: In comparison with time O,
      neither anaphylaxis nor control samples had differences in receptor binding
      parameters with time. There were also no differences between anaphylaxis and
      control lung samples at any time point, and ratios of log control binding
      parameter/log anaphylaxis binding parameter ranged from 0.96 to 1.01.
      CONCLUSIONS: Anaphylaxis of lung does not lead to acute changes in antagonist or
      agonist affinity for beta-receptors or changes in receptor concentration. Under
      the conditions studied, lung mast cell degranulation does not acutely alter the
      human lung beta-receptor system in ways that might account for the beta
      adrenergic hyporesponsiveness found in allergic asthma.

PMID- 8760781
TI  - Comparison between outdoor and indoor airborne allergenic activity.
AB  - BACKGROUND: Allergenic pollens are usually detected in outdoor air by using
      volumetric spore traps, which allow measurement of atmospheric concentration as
      pollen grains per m3 of air. The results of the pollen count are useful primarily
      for outdoor environments while most people spend most of the day indoors.
      OBJECTIVE: The purpose of our study was to compare outdoor pollen levels with
      allergenic activity measured both outdoors and indoors. METHODS: We used a
      Lanzoni spore trap to measure airborne Urticaceae pollen and filters collecting
      particles simultaneously indoors and outdoors and assayed each filter for
      Parietaria judaica allergenic activity. Samples were collected at the
      Allergological Service of the "A. Cardarelli" Hospital in Naples with the balcony
      open on some days and closed on others. Allergenic activity (ng/m3) was measured
      using the immunocapture RAST. RESULTS: With the balcony open there was no great
      difference between outdoor and indoor allergenic activity, but with the balcony
      closed there was a reduction of indoor allergenic activity of about one-third in
      comparison with outdoor allergenic activity. Statistical analysis (Pearson
      correlation test) indicated a significant correlation between outdoor allergen
      levels and indoor allergen levels with the balcony open (r = .4415, P < .05), but
      not with the balcony closed (r = .3160, P > .05); a significant correlation
      between outdoor pollen count and indoor allergen levels with the balcony open (r
      = .4809, P < .05), but not with the balcony closed (r = .3858, P > .05); and a
      highly significant correlation (r = .5225, P < .001) between outdoor pollen count
      and outdoor allergen levels. CONCLUSIONS: These data provide scientific evidence
      for the recommendation to hay fever patients to remain indoors during seasons
      with high levels of outdoor pollens.

PMID- 8760782
TI  - Once daily mometasone furoate aqueous nasal spray is as effective as twice daily
      beclomethasone dipropionate for treating perennial allergic rhinitis patients.
AB  - BACKGROUND: Perennial allergic rhinitis is chronic and persistent, may lead to a
      constellation of secondary complaints including sinusitis, mouth-breathing, and
      some symptoms resembling a permanent cold, and often requires constant medical
      intervention. Well-tolerated nasal corticosteroids, alone or in combination with
      antihistamines, have been found to be very effective in treating this condition.
      OBJECTIVE: To compare the effectiveness and tolerability of mometasone furoate
      aqueous suspension, a new once daily nasal spray, to placebo vehicle and to
      beclomethasone dipropionate, administered twice daily, in patients with perennial
      allergic rhinitis. METHODS: This was a randomized, double-blind, placebo
      controlled, double-dummy, parallel group study, in 427 patients age 12 years and
      older at 24 centers in Canada and Europe. Patients allergic to at least one
      perennial allergen, confirmed by medical history, skin testing, and adequate
      symptomatology were eligible to receive one of the following regimens for 3
      months: mometasone furoate, 200 micrograms only daily; beclomethasone
      dipropionate, 200 micrograms twice daily (400 micrograms total dose); or placebo
      vehicle control. The primary efficacy variable was the change from baseline in
      total AM plus PM diary nasal symptom score over the first 15 days of treatment.
      RESULTS: Three hundred eighty-seven patients were valid for efficacy. For the
      primary efficacy variable, mometasone furoate was significantly (P < or = .01)
      more effective than placebo and was indistinguishable from beclomethasone
      dipropionate. Similar trends were seen among individual symptoms, physician
      symptom evaluations, and therapeutic response. There was no evidence of
      tachyphylaxis. All treatments were well tolerated. CONCLUSIONS: Mometasone
      furoate nasal spray adequately controls symptoms of perennial allergic rhinitis,
      offers the advantage of once daily treatment, and is well tolerated.

PMID- 8760783
TI  - The molecular jury: deciding whether immature thymocytes should live or die.

PMID- 8760784
TI  - Chemoattractants attract HIV researchers.

PMID- 8760785
TI  - Isolation of a nuclease-resistant decoy RNA that selectively blocks autoantibody
      binding to insulin receptors on human lymphocytes.
AB  - An RNA containing 2'-amino pyrimidines has been isolated using in vitro selection
      techniques that specifically and avidly (apparent Kd approximately 30 nM) binds a
      mouse monoclonal antibody called MA20. This 2'-amino-derivatized RNA is at least
      10,000-fold more stable than unmodified RNA in serum, and can act as a decoy and
      block MA20 binding to its natural antigen, the human insulin receptor, on
      lymphocytes. Furthermore, this RNA decoy can inhibit MA20-mediated downmodulation
      of insulin receptor expression on human lymphocytes in culture by up to 90%.
      Surprisingly, the decoy RNA cross-reacts with autoantibodies from patients with
      extreme insulin resistance and can inhibit these antiinsulin receptor antibodies
      from downmodulating insulin receptor expression by up to 80% without impeding
      insulin binding to its receptor. These results suggest that in vitro-selected
      decoy RNAs may be able to specifically and selectively block oligoclonal
      autoimmune responses to self-antigens in patients with autoimmune diseases.

PMID- 8760786
TI  - Differential effects of interleukin-15 and interleukin-2 on differentiation of
      bipotential T/natural killer progenitor cells.
AB  - Bipotential T/natural killer (NK) progenitor cells are destined to differentiate
      mainly into T cell receptor (TCR) alpha beta and TCR gamma delta cells in a
      thymic microenvironment, whereas extrathymically they selectively develop into NK
      cells. The exact environmental conditions that are required for differentiation
      into these three leukocyte populations are largely unknown. In this report, we
      have investigated and compared the effect of interleukin (IL)-15 and IL-2 in this
      process. The IL-15 receptor is composed of the gamma and beta chains of the IL-2
      receptor (IL-2R gamma and IL-2R beta) and of a specific alpha chain (IL-15R
      alpha). Here, it is shown that IL-15 mRNA is mainly expressed in thymic
      epithelial stromal cells, whereas IL-2 mRNA is exclusively expressed in
      thymocytes. IL-2R beta-expressing cells were present in the fetal thymus with a
      CD25-CD44+Fc gamma R+HSA-/low TCR- phenotype, which is characteristic of
      progenitor cells. These cells also expressed IL-15R alpha messenger RNA. Sorted
      IL-2R beta + TCR- cells differentiated into TCR alpha beta and TCR gamma delta
      cells after transfer to alymphoid thymic lobes, whereas culture of the same
      sorted cells in cell suspension in the presence of IL-15 resulted in the
      generation of functional NK cells. This shows that IL-2R beta +TCR- cells of the
      fetal thymus contain bipotential T/NK progenitors. Addition of low concentrations
      of IL-15 to fetal thymic organ culture (FTOC) resulted in an increase of all T
      cell subpopulations. The largest expansion occurred in the TCR gamma delta
      compartment. In contrast, low concentrations of IL-2 did not result in a higher
      total cell number and did not induce outgrowth of TCR gamma delta cells. High
      concentrations of IL-15 blocked TCR alpha beta development and shifted
      differentiation towards NK cells. Differentiation towards TCR gamma delta cells
      still proceeded. High concentrations of IL-2 similarly induced development into
      NK cells, but the cell number was fourfold lower than in IL-15 cultures.
      Importantly, blocking of IL-2R alpha in IL-2-treated FTOC resulted in a drastic
      increase in cell number, indicating that IL-2R alpha negatively regulates cell
      expansion. Collectively, these experiments provide direct evidence that IL-15 and
      IL-2 differentially affect the differentiation of bipotential T/NK progenitors.

PMID- 8760787
TI  - MHC class I molecules form ternary complexes with calnexin and TAP and undergo
      peptide-regulated interaction with TAP via their extracellular domains.
AB  - Newly assembled heavy chain-beta 2m heterodimers of class I histocompatibility
      molecules associate with the endoplasmic reticulum (ER) peptide transporter, TAP,
      and subsequently dissociate from TAP in parallel with their transport from the ER
      to the Golgi apparatus. It appears that TAP-associated class I molecules are
      waiting to bind appropriate peptides before they dissociate from TAP and leave
      the ER since binding of high affinity peptides to class I molecules in vitro
      leads to dissociation of TAP-class I complexes. In further support of this
      notion, we report that limiting peptide supply through inhibition of proteasome
      activities prolongs the association of mouse class I molecules with TAP and
      concomitantly slows their transport to the Golgi apparatus. By using a series of
      deletion mutants and hybrid class I molecules we demonstrate that the
      extracellular domains of class I molecules are sufficient for their peptide
      regulated interaction with TAP. Furthermore, based on the inability of an alpha 3
      domain-specific mAb to recognize TAP-class I complexes and the fact that a point
      mutant of the Dd molecule at residue 222 is unable to bind to TAP, it is likely
      that a major site of interaction with TAP resides in the membrane-proximal region
      of the heavy chain alpha 3 domain. Finally, we examined the relationship between
      the interaction of mouse heavy chain-beta 2m heterodimers with TAP and with the
      resident ER chaperone, calnexin. Most heterodimers that bound to TAP were found
      to associate simultaneously with calnexin. Upon delivery of peptide to class I
      molecules in permeabilized cells, dissociation from TAP was observed but the
      interaction with calnexin was largely maintained. Therefore, both TAP and
      calnexin may participate in the ER retention of peptide-deficient class I
      molecules. However, since release from calnexin occurs after dissociation from
      TAP, it appears that calnexin ultimately determines if a class I molecule is to
      be exported from the ER.

PMID- 8760788
TI  - Both CD4+ and CD8+ T cells are essential to induce experimental autoimmune
      myasthenia gravis.
AB  - CD4+ T cells have been shown to be crucial in the development of experimental
      autoimmune myasthenia gravis (EAMG). The role of CD8+ T cells in EAMG is less
      well established. We previously showed that antibody depletion of CD8+ T cells in
      rats effectively suppresses EAMG. To further study the role and relationship of
      CD4+ versus CD8+ T cells in induction of EAMG, CD4-/-, CD8-/-, and CD4-8- mutant
      C57BL/6 mice and the parent CD4+8- wild-type mice were immunized with Torpedo
      acetylcholine receptor (AChR) plus complete Freund's adjuvant. Clinical EAMG was
      nearly completely prevented in CD4-8-, CD4-/-, and CD8-/- mice. This was
      associated with strongly reduced AChR-specific T and B cell responses, and with
      reduced levels of AChR-reactive interferon gamma (IFN-gamma) and interleukin 4
      (IL-4) mRNA-expressing cells in lymphoid organs when compared with CD4+8+ wild
      type mice. We conclude that (a) both CD4+ and CD8+ T cells are essential for
      development of EAMG, and a collaboration between these cell types may be
      necessary; (b) CD4+ as well as CD8+ T cells secrete IFN-gamma and IL-4, and both
      cytokines are involved in the development of EAMG; and (c), besides T cells,
      other immune cells might also be responsible for help of anti-AChR antibody
      production.

PMID- 8760789
TI  - Histamine selectively enhances human immunoglobulin E (IgE) and IgG4 production
      induced by anti-CD58 monoclonal antibody.
AB  - We studied the effects of histamine on human immunoglobulin (IgE) and IgG4
      production. Histamine selectively enhanced IgE and IgG4 production in purified
      surface IgE and IgG4 negative (sIgE-sIgG4-) B cells from normal donors stimulated
      with interleukin (IL)-4 plus anti-CD58 or IL-13 plus anti-CD58 monoclonal
      antibody (mAb) without affecting production of IgG1, IgG2, IgG3, IgM, IgA1, or
      IgA2. In cultures with IL-4 plus anti-CD58 mAb, histamine-induced enhancement of
      IgE and IgG4 production was specifically blocked by thioperamide (H3 receptor
      antagonist), and was inhibited by anti-IL-10 antibody (Ab). In contrast, in
      cultures with IL-13 plus anti-CD58 mAb, histamine-induced enhancement was blocked
      by dimaprit (H1 receptor antagonist), and was inhibited by anti-IL-6 mAb.
      Histamine also enhanced IgE and IgG4 production by in vivo-generated sIgE+ and
      sIgG4+ B cells, respectively, from atopic patients; enhancement was blocked by
      dimaprit and thioperamide, and was inhibited by anti-IL-6 mAb and anti-IL-10 Ab.
      In sIgE-sIgG4- B cells, IL-4 plus anti-CD58 mAb induced IL-10 production and IL
      10 receptor expression, whereas IL-13 plus anti-CD58 mAb induced IL-6 production
      and IL-6 receptor expression. Histamine increased IL-10 and IL-6 production
      without affecting IL-10 and IL-6 receptor expression, in cultures with IL-4 plus
      anti-CD58 mAb and with IL-13 plus anti-CD58 mAb, respectively, which was blocked
      by thioperamide and dimaprit, respectively. In contrast, sIgE+ and sIgG4+ B cells
      spontaneously produced both IL-6 and IL-10 and constitutively expressed IL-6 and
      IL-10 receptors, and histamine increased IL-6 and IL-10 production without
      affecting IL-6 or IL-10 receptor expression, which was blocked by thioperamide
      and dimaprit. These results indicate that histamine enhanced IgE and IgG4
      production by increasing endogenous IL-6 and IL-10 production via H1 and H3
      receptors, respectively.

PMID- 8760790
TI  - Differential association of protein tyrosine kinases with the T cell receptor is
      linked to the induction of anergy and its prevention by B7 family-mediated
      costimulation.
AB  - When stimulated through their antigen receptor, without costimulation, T cells
      enter a state of antigen-specific unresponsiveness, termed anergy. B7-mediated
      costimulation, signaling via CD28, is sufficient to prevent the induction of
      anergy. Here we show that ligation of T cell receptor (TCR) by alloantigen alone,
      which results in anergy, activates tyrosine phosphorylation of TCR zeta and its
      association with fyn. In contrast, TCR ligation in the presence of B7
      costimulation, which results in productive immunity, activates tyrosine
      phosphorylation of TCR zeta and CD3 chains, which associate with activated lck
      and zeta-associated protein (ZAP) 70. Under these conditions, CD28 associates
      with activated lck and TCR zeta. These data suggest that the induction of anergy
      is an active signaling process characterized by the association of TCR zeta and
      fyn. In addition, CD28-mediated costimulation may prevent the induction of anergy
      by facilitating the effective association of TCR zeta and CD3 epsilon with the
      critical protein tyrosine kinase lck, and the subsequent recruitment of ZAP-70.
      Strategies to inhibit or activate TCR-associated, specific protein tyrosine
      kinase-mediated pathways may provide a basis for drug development with potential
      applications in the fields of transplantation, autoimmunity, and tumor immunity.

PMID- 8760791
TI  - Effect of the laccase gene CNLAC1, on virulence of Cryptococcus neoformans.
AB  - To assess the relationship between melanin production by Cryptococcus neoformans
      and virulence on a molecular basis, we asked: (a) is CNLAC1, the laccase
      structural gene of C. neoformans, expressed in vivo?; (b) can mouse virulence be
      restored to cnlac1 (Mel-) mutants by complementation with CNLAC1?; and (c) will
      targeted gene deletion of CNLAC1 decrease virulence for mice? Melanin is produced
      when cryptococcal laccase catalyzes the oxidation of certain aromatic compounds,
      including L-dopa, to quinones, which then polymerize to melanin. To assess CNLAC1
      transcription, RNA was extracted from C. neoformans in cerebrospinal fluid of
      infected rabbits. Reverse transcriptase-polymerase chain reaction detected CNLAC1
      transcript, indicating that laccase may be produced in the infected host. To
      assess the effect of CNLAC1 deletion on virulence, a Mel- mutant (10S) was
      obtained by disruption of the 5' end of the gene. After multiple backcrosses with
      a parental strain to remove unintended genetic defects introduced by the
      transformation process, a Mel- progeny was tested and found to be much less
      virulent for mice than a Mel+ progeny. Another Mel- strain (mel2), obtained from
      J.C. Edman (University of California at San Francisco, CA), produced CNLAC1
      transcript but no detectable melanin. Characterization of this mutant revealed a
      base substitution in CNLAC1 that changed a histidine to tyrosine in a putative
      copper-binding site. When this base change was introduced into CNLAC1 by site
      directed mutagenesis, it no longer transformed mel2 to Mel+, indicating the
      importance of this histidine in laccase activity. Complementation of a mel2
      derived mutant with CNLAC1 restored the Mel+ phenotype and increased virulence.
      These results support the concept that the CNLAC1 gene product has a role in
      virulence.

PMID- 8760792
TI  - Autoimmune disease as a consequence of developmental abnormality of a T cell
      subpopulation.
AB  - Neonatal thymectomy (NTx), especially around day 3 after birth, causes various
      organ-specific autoimmune diseases in mice. This report shows that: (a) T cells
      expressing the interleukin 2 receptor alpha chains (CD25) ontogenically begin to
      appear in the normal periphery immediately after day 3, rapidly increasing within
      2 wk to nearly adult levels (approximately 10% of CD3+ cells, especially of CD4+
      cells); (b) NTx on day 3 eliminates CD25+ T cells from the periphery for several
      days; inoculation immediately after NTx of CD25+ splenic T cells from syngeneic
      non-Tx adult mice prevents autoimmune development, whereas inoculation of CD25- T
      cells even at a larger dose does not; and furthermore, (c) similar autoimmune
      diseases can be produced in adult athymic nu/nu mice by inoculating either spleen
      cell suspensions from 3-d-old euthymic nu/+ mice or CD25+ cell-depleted spleen
      cell suspensions from older, even 1-yr-old, nu/+ mice. The CD25- populations from
      neonates or adults are also similar in the profile of cytokine formation. These
      results, taken together, indicate that one aspect of peripheral self-tolerance is
      maintained by CD25+ T cells that sustain potentially pathogenic self-reactive T
      cells in a CD25- dormant state; the thymic production of the former is
      developmentally programmed to begin on day 3 after birth in mice. Thus, NTx on
      day 3 can, at least transiently, eliminate/reduce the autoimmune-preventive CD25+
      T cells, thereby leading to activation of the self-reactive T cells that have
      been produced before NTx.

PMID- 8760793
TI  - Cytokine transcriptional events during helper T cell subset differentiation.
AB  - The molecular basis for changes in cytokine expression during T helper (Th) cell
      subset differentiation is not well understood. We have characterized
      transcriptional events related to cytokine gene expression in populations of
      naive T cell receptor-transgenic T cells as they are driven in vitro toward Th1
      or Th2 phenotypes by interleukin (IL)-12 or IL-4 treatment, respectively.
      Quantitative reverse transcriptase-polymerase chain reaction analysis of cytokine
      transcripts indicates that interferon (IFN) gamma, IL-4, and IL-2 mRNA are
      expressed with distinct kinetics after naive T cells are stimulated with antigen
      and either IL-4 or IL-12. IFN-gamma mRNA appears as early as 6 h in IL-12-treated
      cultures, IL-4 appears only after 48 h in IL-4-treated cultures, and IL-2 is
      equivalently expressed in both types of cultures. Analyses were performed to
      determine if there were any differences in activation of IL-2 or IL-4
      transcription factors that accompanied Th1 versus Th2 differentiation. These
      studies demonstrated that signal transducer and activator of transcription 6
      (STAT6) binds to a sequence in the IL-4 promoter and that this STAT6-binding site
      can support IL-4-dependent transcription of a linked heterologous promoter.
      Prolonged activation of STAT6 is characteristic of populations undergoing Th2
      differentiation. Furthermore, STAT6 is activated in an autocrine manner when
      differentiated Th2 populations are stimulated by antigen receptor ligation. Th1
      populations derived from IL-12 plus antigen treatment of naive T cells remain
      responsive to IL-4 as indicated by induction of STAT6 and IL-4 mRNA. These data
      indicate that Th1 and Th2 differentiation represents the combination of
      different, apparently independently regulated transcriptional events.
      Furthermore, among transcription factors that bind to the IL-4 or IL-2 promoters,
      STAT6 is the one whose activation distinguishes Th2 versus Th1 development.

PMID- 8760794
TI  - Induction of cell cycle regulatory proteins in anti-immunoglobulin-stimulated
      mature B lymphocytes.
AB  - Progression through the cell cycle is a tightly controlled process that
      integrates signals generated at the plasma membrane with the proteins that form
      the cell cycle machinery. The current study chronicles the induction of cyclins,
      cyclin-dependent kinases (cdk), and cdk inhibitors in low density primary mouse B
      lymphocytes after anti-immunoglobulin plus interleukin 4 (IgM + IL-4)
      stimulation. In this system, > 85% of cells remain in the G0/G1 phase of cell
      cycle for an initial 24-h period, followed by entry of up to 50% of the cells
      into S phase, commencing around 30 h and peaking at 48 h. Extensive time course
      analyses of these anti-IgM + IL-4-stimulated B cells revealed that the G1
      associated D-type cyclins D2 and D3 were induced by 3 h after stimulation, and
      that cyclins E, A, and B were subsequently induced sequentially, beginning at mid
      G1, G1/S transition, and S phase, respectively. The G1-associated cyclin D1 was
      not expressed at any stage of the anti-Ig + IL-4-induced B cell cycle. cdk2,
      cdk4, and cdk6 were induced during G1, whereas cell division cycle-2 (cdc2) was
      induced concomitantly with S phase. Irrespective of their expression, the kinases
      cdk2 and cdc2 were only active from S phase onwards, suggesting that productive
      cyclin/kinase complex formation did not occur until that time. Cell cycle
      inhibitors p21 and p19 were induced by anti-Ig + IL-4, peaking in expression at
      mid-G1 and S phase, respectively. Stimulation of low density B cells with anti-Ig
      + IL-4 caused rapid down regulation of the p27 inhibitor, however this protein
      was reexpressed at 54-96 h after stimulation. In contrast, B cells stimulated
      with anti-CD40, a stimulus which induces long-term B cell proliferation,
      permanently down regulated p27. These findings are consistent with the concept
      that p27 reexpression contributes to the G1 arrest that follows antigen receptor
      crosslinking. Low density B cells cultured in the viability-enhancing cytokine IL
      4 alone also showed induction of D2 and D3 cyclin expression. However, the D2
      expression was transient, and the D3 expression was substantially lower than that
      observed in B cells induced to proliferate by anti-Ig + IL-4. This partial
      induction of D2 and D3 expression may explain IL-4's ability to promote B cell
      entry into G1 but not S phase of cell cycle, and furthermore, its ability to
      truncate G1 progression when B cells are subsequently stimulated with anti-Ig.

PMID- 8760795
TI  - Transient restoration of gene rearrangement at multiple T cell receptor loci in
      gamma-irradiated scid mice.
AB  - The developmental arrest of thymocytes from scid mice, deficient in variable,
      (diversity), and joining, or V(D)J recombination, can be overcome by sublethal
      gamma-irradiation. Since previous studies focused on restoration of rearrangement
      of the T cell receptor (TCR) beta locus, productive rearrangement of which is
      selected for, we sought to examine to what extent locus specificity and cellular
      selection contributed to the observed effects. We report here that irradiation of
      newborn scid mice induces normal V-D-J rearrangements of the TCR delta locus,
      which like TCR beta, is also actively rearranged in CD(4-)CD(8-) (double
      negative) thymocytes. In contrast, no complete V-J alpha rearrangements were
      detected. Instead, we detected substantial levels of hairpin-terminated coding
      ends at the 5' end of the J alpha locus, demonstrating that TCR alpha
      rearrangements manifest the effects of the scid mutation. Irradiation, therefore,
      transiently compensates for the effects of the scid mutation in a locus
      nonspecific manner in thymocytes, resulting in a burst of normal TCR beta and
      delta rearrangements. Irradiation also allows the development of cells that can
      initiate but fail to complete V(D)J recombination events at the TCR alpha locus,
      which is normally inaccessible in scid thymocytes.

PMID- 8760797
TI  - Loss of a unique tumor antigen by cytotoxic T lymphocyte immunoselection from a 3
      methylcholanthrene-induced mouse sarcoma reveals secondary unique and shared
      antigens.
AB  - Most chemically induced tumors of mice express unique antigens that can be
      recognized by cytotoxic T lymphocytes (CTL) and thereby mediate tumor rejection.
      The number of different antigens expressed by a single tumor and their interplay
      during immunization and rejection are largely unexplored. We used CTL clones
      specific to individual tumor antigens to examine the number and distribution of
      CTL antigens expressed by cell lines derived from 3-methylcholanthrene-induced
      sarcomas of (C57BL/6J X SPRET/Ei)F1 mice. Each tumor cell line expressed one or
      more antigens that were unique, that is, not detected on cell lines from
      independent sarcomas. Immunoselection against an immunodominant antigen produced
      both major histocompatibility complex class I antigen and unique tumor antigen
      loss variants. Immunization of mice with antigen-negative immunoselected variants
      resulted in CTL that recognized additional antigens that were also expressed by
      the progenitor tumor. Some CTL recognized additional unique tumor antigen(s);
      other CTL recognized a shared antigen expressed not only by the immunizing cell
      line, but also by independent sarcoma cell lines and untransformed myoblastoid
      cell lines. CTL that recognized the shared antigen were also recovered from mice
      immunized in vivo with an untransformed myoblastoid cell line. These findings
      support a model of immunodominance among chemically induced tumor antigens in
      which shared antigens are masked by unique immunodominant antigens.

PMID- 8760796
TI  - Differential expression of Fas (CD95) and Fas ligand on normal human phagocytes:
      implications for the regulation of apoptosis in neutrophils.
AB  - Human neutrophils, monocytes, and eosinophils are known to undergo apoptotic cell
      death. The Fas/Fas ligand pathway has been implicated as an important cellular
      pathway mediating apoptosis in diverse cell types. We conducted studies to
      examine the importance of the Fas/FasL system in normal human phagocytes.
      Although Fas expression was detected on neutrophils, monocytes, and eosinophils,
      constitutive expression of FasL was restricted to neutrophils. The three types of
      phagocytes demonstrated differential sensitivity to Fas-induced apoptosis. Only
      neutrophils were highly susceptible to rapid apoptosis in vitro after stimulation
      with activating anti-Fas IgM (mAb CH-11). Fas-mediated neutrophil apoptosis was
      suppressed by incubation with G-CSF, GM-CSF, IFN-gamma, TNF-alpha, or
      dexamethasone, as well as the selective tyrosine kinase inhibitors, herbimycin A
      and genistein. Spontaneous neutrophil death in vitro was partially suppressed by
      Fas-Ig fusion protein or antagonistic anti-Fas IgG1 (mAb ZB4). In coculture
      experiments, neutrophils released a soluble factor inducing death in Fas
      susceptible Jurkat cells via a mechanism sensitive to the presence of Fas-Ig or
      anti-Fas IgG1. Immunoblot analysis using specific anti-human FasL IgG1 (mAb No.
      33) identified a 37-kD protein in lysates of freshly isolated neutrophils and a
      30-kD protein in the culture supernatant of neutrophils maintained in vitro. Our
      results suggest that mature neutrophils may be irrevocably committed to autocrine
      death by virtue of their constitutive coexpression of cell-surface Fas and FasL
      via a mechanism that is sensitive to proinflammatory cytokines, glucocorticoids,
      and inhibitors of tyrosine kinase activity. Furthermore, neutrophils can serve as
      a source of soluble FasL, which may function in a paracrine pathway to mediate
      cell death.

PMID- 8760798
TI  - Type 3-specific synthase of Streptococcus pneumoniae (Cap3B) directs type 3
      polysaccharide biosynthesis in Escherichia coli and in pneumococcal strains of
      different serotypes.
AB  - The cap3B gene, which is involved in the formation of the capsule of
      Streptococcus pneumoniae type 3, encodes a 49-kD protein that has been identified
      as a polysaccharide synthase. Escherichia coli cells harboring the recombinant
      plasmid pTBP3 (cap3B) produced pneumococcal type 3 polysaccharide, as
      demonstrated by immunological tests. Biochemical and cell fractionation analyses
      revealed that this polysaccharide had a high molecular mass and was localized in
      substantial amounts in the periplasmic space of E. coli. Unencapsulated (S-2),
      laboratory pneumococcal strains synthesized type 3 polysaccharide by
      transformation with plasmid pLSE3B harboring cap3B. In addition, encapsulated
      pneumococci of types 1, 2, 5, or 8 transformed with pLSE3B can direct the
      synthesis of pneumococcal type 3 polysaccharide, leading to the formation of
      strains that display binary type of capsule.

PMID- 8760799
TI  - Hematopoietic cell phosphatase, SHP-1, is constitutively associated with the SH2
      domain-containing leukocyte protein, SLP-76, in B cells.
AB  - Src homology region 2 (SH2) domain-containing phosphatase 1 (SHP-1; previously
      named HCP, PTP1C, SH-PTP1, and SHP) is a cytosolic protein tyrosine phosphatase
      that contains two SH2 domains. Recent data have demonstrated that the gene
      encoding SHP-1 is mutated in motheaten (mc) and viable motheaten (mc') mice
      resulting in autoimmune disease. More recently, SHP-1 has been shown to
      negatively regulate B cell antigen receptor (BCR)-initiated signaling. To
      elucidate potential mechanisms of SHP-1 action in BCR signal transduction, we
      studied proteins that interact with SHP-1 in B cells. Both anti-SHP-1 antibody
      and the two SH2 domains of SHP-1 expressed as glutathione S-transferase fusion
      proteins precipitated at least three phosphoproteins of approximately 75, 110,
      and 150 kD upon anti-immunoglobulin M stimulation of the WEHI-231 immature B cell
      line. Binding of SHP-1 to the 75- and 110-kD proteins appeared to be mediated
      mainly by the NH2-terminal SH2 domain of SHP-1, whereas both the NH2- and COOH
      terminal SH2 domains are required for maximal binding to the 150-kD protein.
      Immunoprecipitation and Western blot analysis revealed that the SHP-1-associated
      75-kD protein is the hematopoietic cell-specific, SH2-containing protein SLP-76.
      Further, this protein-protein association was constitutively observed and stable
      during the early phase of BCR signaling. However, significant tyrosine
      phosphorylation of SLP-76 as well as of SHP-1 was observed after BCR ligation.
      Constitutive association of SHP-1 with SLP-76 could also be detected in normal
      splenic B cells. Collectively, these results suggest possible mechanisms by which
      SHP-1 may modulate signals delivered by BCR engagement.

PMID- 8760800
TI  - Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and
      in vivo.
AB  - Immunization with defined tumor antigens is currently limited to a small number
      of cancers where candidates for tumor rejection antigens have been identified. In
      this study we investigated whether pulsing dendritic cells (DC) with tumor
      derived RNA is an effective way to induce CTL and tumor immunity. DC pulsed with
      in vitro synthesized chicken ovalbumin (OVA) RNA were more effective than OVA
      peptide-pulsed DC in stimulating primary, OVA-specific CTL responses in vitro. DC
      pulsed with unfractionated RNA (total or polyA+) from OVA-expressing tumor cells
      were as effective as DC pulsed with OVA peptide at stimulating CTL responses.
      Induction of OVA-specific CTL was abrogated when polyA+ RNA from OVA-expressing
      cells was treated with an OVA-specific antisense oligodeoxynucleotide and RNase
      H, showing that sensitization of DC was indeed mediated by OVA RNA. Mice
      vaccinated with DC pulsed with RNA from OVA-expressing tumor cells were protected
      against a challenge with OVA-expressing tumor cells. In the poorly immunogenic,
      highly metastatic, B16/F10.9 tumor model a dramatic reduction in lung metastases
      was observed in mice vaccinated with DC pulsed with tumor-derived RNA (total or
      polyA+, but not polyA- RNA). The finding that RNA transcribed in vitro from cDNA
      cloned in a bacterial plasmid was highly effective in sensitizing DC shows that
      amplification of the antigenic content from a small number of tumor cells is
      feasible, thus expanding the potential use of RNA-pulsed DC-based vaccines for
      patients bearing very small, possibly microscopic, tumors.

PMID- 8760801
TI  - Differentiation and stability of T helper 1 and 2 cells derived from naive human
      neonatal CD4+ T cells, analyzed at the single-cell level.
AB  - The development of CD4+ T helper (Th) type 1 and 2 cells is essential for the
      eradication of pathogens, but can also be responsible for various pathological
      disorders. Therefore, modulation of Th cell differentiation may have clinical
      utility in the treatment of human disease. Here, we show that interleukin (IL) 12
      and IL-4 directly induce human neonatal CD4- T cells, activated via CD3 and CD28,
      to differentiate into Th1 and Th2 subsets. In contrast, IL-13, which shares many
      biological activities with IL-4, failed to induce T cell differentiation,
      consistent with the observation that human T cells do not express IL-13
      receptors. Both the IL-12-induced Th1 subset and the IL-4-induced Th2 subset
      produce large quantities of IL-10, confirming that human IL-10 is not a typical
      human Th2 cytokine. Interestingly, IL-4-driven Th2 cell differentiation was
      completely prevented by an IL-4 mutant protein (IL-4.Y124D), indicating that this
      molecule acts as a strong IL-4 receptor antagonist. Analysis of single T cells
      producing interferon gamma or IL-4 revealed that induction of Th1 cell
      differentiation occurred rapidly and required only 4 d of priming of the neonatal
      CD4+ T cells in the presence of IL-12. The IL-12-induced Th1 cell phenotype was
      stable and was not significantly affected when repeatedly stimulated in the
      presence of recombinant IL-4. In contrast, the differentiation of Th2 cells
      occurred slowly and required not only 6 d of priming, but also additional
      restimulation of the primed CD4+ T cells in the presence of IL-4. Moreover, IL-4
      induced Th2 cell phenotypes were not stable and could rapidly be reverted into a
      population predominantly containing Th0 and Th1 cells, after a single
      restimulation in the presence of IL-12. The observed differences in stability of
      IL-12- and IL-4-induced human Th1 and Th2 subsets, respectively, may have
      implications for cytokine-based therapies of chronic disease.

PMID- 8760802
TI  - Role of antigen, CD8, and cytotoxic T lymphocyte (CTL) avidity in high dose
      antigen induction of apoptosis of effector CTL.
AB  - Experimental data suggest that negative selection of thymocytes can occur as a
      result of supraoptimal antigenic stimulation. It is unknown, however, whether
      such mechanisms are at work in mature CD8+ T lymphocytes. Here, we show that CD8+
      effector cytotoxic T lymphocytes (CTL) are susceptible to proliferative
      inhibition by high dose peptide antigen, leading to apoptotic death mediated by
      TNF-alpha release. Such inhibition is not reflected in the cytolytic potential of
      the CTL, since concentrations of antigen that are inhibitory for proliferation
      promote efficient lysis of target cells. Thus, although CTL have committed to the
      apoptotic pathway, the kinetics of this process are such that CTL function can
      occur before death of the CTL. The concentration of antigen required for
      inhibition is a function of the CTL avidity, in that concentrations of antigen
      capable of completely inhibiting high avidity CTL maximally stimulate low avidity
      CTL. Importantly, the inhibition can be detected in both activated and resting
      CTL. Blocking studies demonstrate that the CD8 molecule contributes significantly
      to the inhibitory signal as the addition of anti-CD8 antibody restores the
      proliferative response. Thus, our data support the model that mature CD8+ CTL can
      accommodate an activation signal of restricted intensity, which, if surpassed,
      results in deletion of that cell.

PMID- 8760803
TI  - Immune deviation of 2C transgenic intraepithelial lymphocytes in antigen-bearing
      hosts.
AB  - The present study examined self-tolerance for T cell receptor (TCR) alpha beta
      intestinal intraepithelial lymphocytes (iIELs) using the 2C transgenic (Tg) mouse
      model specific for a peptide antigen (Ag) presented by the class I major
      histocompatibility complex H-2Ld. Although Tg+ T cells were largely deleted from
      the periphery of Ag+ mice, equivalent numbers of Tg iIELs were present in Ag+
      compared to Ag- mice. Tg iIELs in Ag- mice contained CD8 alpha beta, CD8 alpha
      alpha, and CD4-CD8- subsets, whereas only CD8 alpha alpha and CD4-CD8- Tg iIEL
      subsets were detected in Ag+ mice. Analysis of surface markers revealed that Tg
      iIELs in Ag+ mice expressed decreased levels of Thy-1 and increased CD45R/B220 as
      compared to Ag- Tg iIELs. In response to activation with exogenous peptide or
      immobilized anti-TCR mAB, iIELs from Ag- mice proliferated at high levels and
      produced interleukin (IL)-2 and interferon (IFN)-gamma, while Tg+ iIELs from Ag+
      mice proliferated at low levels and failed to produce detectable IL-2 or IFN
      gamma. Activation of sorted iIEL subsets from Ag- mice revealed that CD8 alpha
      alpha and CD4-CD8- subsets produced low levels of IL-2 and IFN-gamma in response
      to activation with antigen-presenting cells and added peptide or immobilized anti
      TCR mAb, while CD8 alpha beta + iIELs responded to endogenous levels of peptide.
      In response to APC and exogenous peptide, sorted iIEL subsets from Ag+ mice
      produced IL-2 and IFN-gamma, and proliferated at greatly reduced levels compared
      to corresponding subsets from Ag- mice. Analysis of cytokine mRNA levels revealed
      that activation in vitro induced IL-2 mRNA only in Ag-, but not Ag+ iIELs,
      whereas a high level of IL-4 mRNA induction was detected in Tg+ iIELs from Ag+
      mice, and to a lesser degree, from Ag- mice. These data suggest that tolerance
      for Tg+ iIELs resulted in the deletion of CD8 alpha beta + subsets and the
      persistence of Tg+ iIEL subsets with decreased sensitivity to endogenous levels
      of self-peptide. A comparison of the cytokine profiles expressed by Tg+ iIEL
      subsets in Ag- and Ag+ mice suggested that tolerance induction had involved the
      functional deviation of cells from TC1 (T helper-1-like) to a less inflammatory
      TC2 (T helper-2-like) phenotype capable of mediating humoral immune responses in
      the mucosa.

PMID- 8760804
TI  - The natural killer cell receptor specific for HLA-A allotypes: a novel member of
      the p58/p70 family of inhibitory receptors that is characterized by three
      immunoglobulin-like domains and is expressed as a 140-kD disulphide-linked dimer.
AB  - Human natural killer (NK) cells express inhibitory receptors that are specific
      for different groups of HLA-C or HLA-B alleles. The majority of these receptors
      belong to the immunoglobulin (Ig) superfamily and are characterized by two or
      three extracellular Ig-like domains. Here we describe a novel inhibitory NK
      receptor that is specific for a group of HLA-A alleles. The HLA-A3-specific NK
      cell clone DP7 has been used for mice immunization. Two mAbs, termed Q66 and
      Q241, bound to the immunizing clone and stained only a subset of NK cell
      populations or clones. Among Q66 mAb-reactive clones, we further selected those
      that did not express any of the previously identified HLA-class I-specific NK
      receptors. These clones did not lyse HLA-A3+ (or -A11+) target cells, but lysis
      of these targets could be detected in the presence of Q66 or Q241 mAbs. On the
      other hand, target cells expressing other HLA-A alleles, including -A1, -A2, and 
      A24, were efficiently lysed. Moreover, none of the HLA-C or HLA-B alleles that
      were tested exerted a protective effect. Q66+, but not Q66- NK cell clones,
      expressed messenger RNA coding for a novel 3 Ig domain protein homologous to the
      HLA-C (p58) and HLA-B (p70) receptors. The corresponding cDNA (cl.1.1) was used
      to generate transient and stable transfectants in COS7 and NIH3T3 cell lines,
      respectively. Both types of transfectants were specifically stained by Q66 and
      Q241 mAbs. Since the cytoplasmic tail of Q66-reactive molecules was at least 11
      amino acid longer than the other known p58/p70 molecules, we could generate an
      antiserum specific for the COOH-terminus of Q66-reactive molecules, termed PGP-3.
      PGP-3 immunoprecipitated, only from Q66+ NK cells, molecules displaying a
      molecular mass of 140 kD, under nonreducing conditions, which resolved, under
      reducing conditions, in a 70-kD band. Thus, differently from the other p58/p70
      receptors, Q66-reactive molecules appear to be expressed as disulphide-linked
      dimers and were thus termed p140. The comparative analysis of the amino acid
      sequences of p58, p70, and p140 molecules revealed the existence of two cysteins
      proximal to the transmembrane region, only in the amino acid sequence of p140
      molecules.

PMID- 8760805
TI  - Regulation of pre-T cell receptor (pT alpha-TCR beta) gene expression during
      human thymic development.
AB  - In murine T cell development, early thymocytes that productively rearrange the T
      cell receptor (TCR) beta locus are selected to continue maturation, before TCR
      alpha expression, by means of a pre-TCR alpha- (pT alpha-) TCR beta heterodimer
      (pre-TCR). The aim of this study was to identify equivalent stages in human
      thymocyte development. We show here that variable-diversity-joining region TCR
      beta rearrangement and the expression of full-length TCR beta transcripts have
      been initiated in some immature thymocytes at the TCR alpha/beta- CD4+CD8- stage,
      and become common in a downstream subset of TCR alpha/beta- CD4+CD8+ thymocytes
      that is highly enriched in large cycling cells. TCR beta chain expression was
      hardly detected in TCR alpha/beta- CD4+CD8- thymocytes, whereas cytoplasmic TCR
      beta chain was found in virtually all TCR alpha/beta- CD4+CD8+ blasts. In
      addition, a TCR beta complex distinct from the mature TCR alpha/beta heterodimer
      was immunoprecipitated only from the latter subset. cDNA derived from TCR
      alpha/beta- CD4+CD8+ blasts allowed us to identify and clone the gene encoding
      the human pT alpha chain, and to examine its expression at different stages of
      thymocyte development. Our results show that high pT alpha transcription occurs
      only in CD4+CD8- and CD4+CD8+ TCR alpha/beta- thymocytes, whereas it is weaker in
      earlier and later stages of development. Based on these results, we propose that
      the transition from TCR alpha/beta- CD4+CD8- to TCR alpha/beta- CD4+CD8+
      thymocytes represents a critical developmental stage at which the successful
      expression of TCR beta promotes the clonal expansion and further maturation of
      human thymocytes, independent of TCR alpha.

PMID- 8760806
TI  - Differing roles for B7 and intercellular adhesion molecule-1 in negative
      selection of thymocytes.
AB  - To ensure self tolerance, immature thymocytes with high binding affinity for self
      peptides linked to major histocompatibility complex (MHC) molecules are
      eliminated in situ via apoptosis (negative selection). The roles of two
      costimulatory molecules, B7-1 and intercellular adhesion molecule-1 (ICAM-1), in
      negative selection was examined by studying apoptosis of T cell receptor
      transgenic CD4+8+ thymocytes cultured with specific peptides presented by MHC
      class I-transfected Drosophila cells. When coexpressed on these cells, B7-1 and
      ICAM-1 act synergistically and cause strong class 1-restricted negative selection
      of thymocytes. When expressed separately, however, B7-1 and ICAM-1 display
      opposite functions: negative selection is augmented by B7-1, but is inhibited by
      ICAM-1. It is notable that B7-1 is expressed selectively in the thymic medulla,
      whereas ICAM-1 is expressed throughout the thymus. Because of this distribution,
      the differing functions of B7-1 and ICAM-1 may dictate the sites of positive and
      negative selection. Thus, in the cortex, the presence of ICAM-1, but not B7-1, on
      the cortical epithelium may preclude or reduce negative selection and thereby
      promote positive selection. Conversely, the combined expression of B7-1 and ICAM
      1 may define the medulla as the principal site of negative selection.

PMID- 8760807
TI  - Human placental cytotrophoblasts produce the immunosuppressive cytokine
      interleukin 10.
AB  - The mechanism by which the mammalian mother accepts the implanting fetus as an
      allograft remains unexplained, but is likely to be the result of a combination of
      factors. Mononuclear cytotrophoblasts, the specialized fetal cells of the
      placenta that invade the uterus, play an important role. These cells express HLA
      G, an unusual major histocompatibility complex class I-B molecule, and secrete
      cytokines and pregnancy-specific proteins that can regulate immune function. We
      investigated whether cytotrophoblasts secrete interleukin 10 (IL-10), a cytokine
      that potently inhibits alloresponses in mixed lymphocyte reactions.
      Cytotrophoblasts from all stages of pregnancy produced IL-10 in vitro, but
      neither placental fibroblasts nor choriocarcinoma (malignant trophoblast) cell
      lines did so. Spontaneous IL-10 production averaged 650, 853, and 992 pg/10(6)
      cells in the first, second, and third trimesters of pregnancy, respectively. IL
      10 secretion dropped approximately 10-fold after the first 24 h of culture, and
      was paralleled by a decrease in messenger RNA. IL-10 messenger RNA was detected
      in biopsies of the placenta and the portion of the uterus that contains invasive
      cytotrophoblasts, suggesting that this cytokine is also produced in vivo. IL-10
      secreted by cytotrophoblasts in vitro is bioactive, as determined by its ability
      to suppress interferon gamma production in an allogeneic mixed lymphocyte
      reaction. We conclude that human cytotrophoblast IL-10 may be an important factor
      that contributes to maternal tolerance of the allogeneic fetus.

PMID- 8760808
TI  - Retro-retinoids in regulated cell growth and death.
AB  - Vitamin A serves as a prohormone from which three classes of active metabolites
      are derived: the aldehydes, the carboxylic acids, and the retro-retinoids.
      Although these three classes are united under the rubric of signal transduction,
      they act by different molecular mechanisms: the 11-cis-retinaldehydes combine
      with opsin to form the universal visual pigments and the retinoic acids form
      ligands for transcription factors, whereas the retro-retinoids, as shown here,
      intersect with signal transduction at a cytoplasmic or membrane site. The retro
      retinoid, anhydroretinol (AR), has long been known to act as a growth inhibitor
      in lymphocytes, whereas 14-hydroxy-4,14-retro-retinol (14-HRR) is required for
      normal lymphocyte proliferation. A mutually reversible relationship exists
      between these two retro-retinoids as one can reverse the effects of the other
      when given in pharmacological doses. The common explanation for reversible
      inhibition is competition for a shared receptor. We now provide evidence that
      when AR is given to T cells unmitigated by 14-HRR, rapid cell death can occur.
      The circumstances are closely related to nonclassical forms of apoptosis: within
      2 h of AR administration the T cells undergo widespread morphological changes,
      notably surface blebbing and ballooning and, inevitably, bursting. In contrast,
      nuclear changes are comparatively mild, as indicated by absence of chromatin
      condensation and overt DNA cleavage to discrete nucleosomal fragments, although
      DNA nicks are readily discernible by terminal deoxynucleotidyl transferase assay.
      What further distinguishes the AR-induced form of apoptosis from classical ones
      is a lack of requirements of messenger RNA and protein synthesis, suggesting that
      the events leading to cell death are primarily initiated and play themselves out
      in the cytoplasm. This view is further reinforced by the finding that herbimycin
      A can prevent the onset of programmed cell death. The importance of our findings
      is that they strongly suggest a second messenger role for vitamin A metabolites
      in the cytoplasmic realm that has not been seen previously. These findings are
      entirely compatible with a general notion that in a cell requiring multiple
      coordinated signals for survival, the provision of an unbalanced signal can
      initiate programmed cell death. Collectively, our data also challenge the
      paradigm that retinoids (outside vision) solely mediate their function via the
      steroid/ retinoic acid receptor family of nuclear transcription factors. Instead,
      a mode of action in the cytoplasmic realm akin to one attributed to other small
      lipophilic second messenger molecules, such as diacyl glycerol or ceramide, may
      apply to retro-retinoids.

PMID- 8760809
TI  - Nitric oxide in Tanzanian children with malaria: inverse relationship between
      malaria severity and nitric oxide production/nitric oxide synthase type 2
      expression.
AB  - Nitric oxide (NO)-related activity has been shown to be protective against
      Plasmodium falciparum in vitro. It has been hypothesized, however, that excess NO
      production contributes to the pathogenesis of cerebral malaria. The purpose of
      this study was to compare markers of NO production [urinary and plasma nitrate +
      nitrite (NOx)], leukocyte-inducible nitric oxide synthase type 2 (NOS2), and
      plasma TNF-alpha and IL-10 levels with disease severity in 191 Tanzanian children
      with and without malaria. Urine NOx excretion and plasma NOx levels (corrected
      for renal impairment) were inversely related to disease severity, with levels
      highest in subclinical infection and lowest in fatal cerebral malaria. Results
      could not be explained by differences in dietary nitrate ingestion among the
      groups. Plasma levels of IL-10, a cytokine known to suppress NO synthesis,
      increased with disease severity. Leukocyte NOS2 antigen was detectable in all
      control children tested and in all those with subclinical infection, but was
      undetectable in all but one subject with cerebral malaria. This suppression of NO
      synthesis in cerebral malaria may contribute to pathogenesis. In contrast, high
      fasting NOx levels and leukocyte NOS2 in healthy controls and asymptomatic
      infection suggest that increased NO synthesis might protect against clinical
      disease. NO appears to have a protective rather than pathological role in African
      children with malaria.

PMID- 8760810
TI  - Interleukin-2 regulates CC chemokine receptor expression and chemotactic
      responsiveness in T lymphocytes.
AB  - Several studies have shown that CC chemokines attract T lymphocytes, and that
      CD45RO+, memory phenotype cells are considered to be the main responders. The
      results, however, have often been contradictory and the role of lymphocyte
      activation and proliferation has remained unclear. Using CD45RO+ blood
      lymphocytes cultured under different stimulatory conditions, we have now studied
      chemotaxis as well as chemokine receptor expression. Expression of the RANTES/MIP
      1 alpha receptor (CC-CKR1) and the MCP-1 receptor (CC-CKR2) was highly correlated
      with migration toward RANTES, MCP-1, and other CC chemokines, and was strictly
      dependent on the presence of IL-2 in the culture medium. Migration and receptor
      expression were rapidly downregulated when IL-2 was withdrawn, but were fully
      restored when IL-2 was added again. The effect of IL-2 could be partially
      mimicked by IL-4, IL-10, or IL-12, but not by IL-13, IFN gamma, IL-1 beta, TNF
      alpha, or by exposure to anti-CD3, anti-CD28 or phytohemagglutinin. Activation of
      fully responsive lymphocytes through the TCR/CD3 complex and CD28 antigen
      actually had the opposite effect. It rapidly downregulated receptor expression
      and consequent migration even in the presence of IL-2. In contrast to the effects
      on CC chemokine receptors, stimulation of CD45RO+ T lymphocytes with IL-2 neither
      induced the expression of the CXC chemokine receptors, IL8-R1 and IL8-R2, nor
      chemotaxis to IL-8. The prominent role of IL-2 in CC chemokine responsiveness of
      lymphocytes suggests that IL-2-mediated expansion is a prerequisite for the
      recruitment of antigen-activated T cells into sites of immune and inflammatory
      reactions.

PMID- 8760811
TI  - Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanism.
AB  - Interleukin-10 (IL-10) is a recently described pleiotropic cytokine secreted
      mainly by type 2 helper T cells. Previous studies have shown that IL-10
      suppresses cytokine expression by natural killer (NK) and type 1 T cells, thus
      down-regulating cell-mediated immunity and stimulating humoral responses. We here
      report that injected IL-10 protein is an efficient inhibitor of tumor metastasis
      in experimental (B16-F10) and spontaneous (M27 and Lox human melanoma) metastasis
      models in vivo at doses that do not have toxic effects on normal or cancer cells.
      Histological characterization after IL-10 treatment confirmed the absence of CD8+
      and CD4+ T cells and macrophages at the sites of tumor growth, but abundant NK
      cells were localized at these sites. This unexpected finding was confirmed by
      showing that IL-10 inhibits most B16-F10 and Lox metastases in mice deficient in
      T or B cells (SCID and nu/nu mice), but not in those deficient in NK cells (beige
      mice or NK cell-depleted mice). However, IL-10 downregulation of pro-inflammatory
      cytokine production and/or recruitment of additional effector cells may also be
      involved in the anti-tumor effect at higher local concentrations of IL-10, since
      transfected B16 tumor cells expressing high amounts of IL-10 were rejected by
      normal, nu/nu, or SCID mice at the primary tumor stage, and there was still a 33%
      inhibition of tumor metastasis in beige mice.

PMID- 8760812
TI  - Activation of phospholipase D is tightly coupled to the phagocytosis of
      Mycobacterium tuberculosis or opsonized zymosan by human macrophages.
AB  - Phagocytosis of Mycobacterium tuberculosis by human mononuclear phagocytes is
      mediated primarily by complement receptors (CRs) but the transmembrane signaling
      mechanisms that regulate phagocytosis of the bacterium are unknown. We have
      analyzed the activation of phospholipase D (PLD) during phagocytosis of the
      virulent Erdman and attenuated H37Ra strains of M. tuberculosis by human monocyte
      derived macrophages (MDMs), radiolabeled with [3H]-lyso-phosphatidylcholine.
      Phagocytosis of either Erdman or H37Ra M. tuberculosis in the presence of
      autologous non-immune serum was associated with a 2.5-3-fold increase in
      phosphatidic acid (PA). Definitive evidence for activation of PLD by M.
      tuberculosis was provided by markedly increased generation of the PLD-specific
      product phosphatidylethanol (PEt) (9.9-fold increases in [3H]-PEt for both Erdman
      and H37Ra strains compared to control, P < 0.001, n = 12), in the presence of
      0.5% ethanol. Phagocytosis of opsonized zymosan (OZ), which is also mediated by
      CRs, was similarly associated with activation of PLD (12.2-fold increase in PEt,
      P < 0.001, n = 12). The competitive PLD inhibitor 2,3-diphosphoglycerate (2,3
      DPG) produced concentration-dependent inhibition of PLD activity stimulated by
      either M. tuberculosis (-78 +/- 8%) or OZ (-73 +/- 6%). Inhibition of PLD by 2,3
      DPG was associated with concentration-dependent reductions in phagocytosis of M.
      tuberculosis (-74 +/- 4%) and OZ (-68 +/- 5%). Addition of purified PLD from
      Streptomyces chromofuscus to 2,3-DPG-treated macrophages restored phagocytosis of
      M. tuberculosis to control levels. Inhibition of M. tuberculosis- or OZ
      stimulated PA generation by ethanol was associated with concentration-dependent
      reductions in phagocytosis of both particles. Incubation of MDMs with either
      Erdman or H37Ra M. tuberculosis, or OZ, resulted in rapid (onset 1 min) and
      sustained (60 min) increases in the tyrosine phosphorylation (Tyr-P) of multiple
      MDM proteins. Prominent Tyr-P was noted in proteins of 150, 95, 72, 56, and 42
      kD. The protein tyrosine kinase (PTK) inhibitors genistein and herbimycin A
      reduced M. tuberculosis-stimulated PLD activity by 66-84%. Inhibition of PLD
      activity by genistein or herbimycin A was associated with inhibition of
      phagocytosis of M. tuberculosis and OZ. These data demonstrate that PLD is
      activated during macrophage phagocytosis of M. tuberculosis or OZ, that PTKs are
      involved in this stimulation of PLD, and that the extent of phagocytosis of these
      particles is tightly coupled to activation of PLD.

PMID- 8760813
TI  - Association of CD4+ T cell-dependent, interferon-gamma-mediated necrosis of the
      small intestine with genetic susceptibility of mice to peroral infection with
      Toxoplasma gondii.
AB  - Since there is a remarkable difference in susceptibility to peroral infection
      with Toxoplasma gondii among inbred strains of mice, we performed studies to
      examine the mechanism(s) of this difference in susceptibility. After peroral
      infection with the ME49 strain of T. gondii, C57BL/6 (B6) mice all died whereas
      BALB/c mice all survived. At day 7 of infection (when B6 mice began dying),
      massive necrosis of the villi and mucosal cells in the ilea were observed in B6
      but not in BALB/c mice. To analyze the role of T cells in resistance against
      death and development of necrosis in the ilea after infection, studies were
      performed using athymic nude and euthymic control B6 and BALB/c mice. Athymic B6
      mice all died after infection, but surprisingly, they survived significantly
      longer than control B6 mice, indicating that T cells predispose to early death in
      these mice. Necrosis in the ilea was observed in control B6 but not in athymic B6
      mice; however, significantly less numbers of tachyzoites were observed in the
      ilea of the former than the latter mice. These results indicate that necrosis in
      the ilea of the B6 mice was not due to destruction of tissue by tachyzoites but
      was mediated by T cells. This deleterious effect of T cells appears to contribute
      to early death in these mice. In contrast, T cells conferred resistance against
      death in BALB/c mice but did not cause necrosis in their ilea. To analyze the T
      cell subset(s) that induces necrosis of the ilea in B6 mice, we examined
      histological changes of the small intestines after infection of mutant mice
      deficient in different T cell subsets (with the same H-2b haplotype as B6 mice).
      Mice deficient in alpha/beta or CD4+ T cells did not develop necrosis in the
      ilea, whereas wild-type control mice and mice deficient in gamma/delta or CD8+ T
      cells did, suggesting that the cells that induce necrosis in the ilea after
      infection are CD4+ alpha/beta T cells. Since interferon (IFN)-gamma has been
      shown to be critical for survival of BALB/c mice after infection with T. gondii,
      we examined the role of this cytokine in resistance/susceptibility of infected B6
      mice. Treatment of B6 mice with anti-IFN-gamma monoclonal antibody shortly before
      they developed illness prolonged time to death and prevented necrosis in the ilea
      in these mice. These results indicate that IFN-gamma mediates necrosis in the
      ilea of B6 mice after infection. This CD4+ T cell-dependent, IFN-gamma-mediated
      necrosis of the small intestines appears to be a mechanism that underlies the
      genetic susceptibility of B6 mice to peroral infection with T. gondii, whereas
      the same cytokine plays a critical role in the resistance of genetically
      resistant BALB/c mice.

PMID- 8760814
TI  - Selective loss of sarcolemmal nitric oxide synthase in Becker muscular dystrophy.
AB  - Becker muscular dystrophy is an X-linked disease due to mutations of the
      dystrophin gene. We now show that neuronal-type nitric oxide synthase (nNOS), an
      identified enzyme in the dystrophin complex, is uniquely absent from skeletal
      muscle plasma membrane in many human Becker patients and in mouse models of
      dystrophinopathy. An NH2-terminal domain of nNOS directly interacts with alpha 1
      syntrophin but not with other proteins in the dystrophin complex analyzed.
      However, nNOS does not associate with alpha 1-syntrophin on the sarcolemma in
      transgenic mdx mice expressing truncated dystrophin proteins. This suggests a
      ternary interaction of nNOS, alpha 1-syntrophin, and the central domain of
      dystrophin in vivo, a conclusion supported by developmental studies in muscle.
      These data indicate that proper assembly of the dystrophin complex is dependent
      upon the structure of the central rodlike domain and have implications for the
      design of dystrophin-containing vectors for gene therapy.

PMID- 8760815
TI  - Interleukin-1 beta-converting enzyme-like protease cleaves DNA-dependent protein
      kinase in cytotoxic T cell killing.
AB  - Cytotoxic T cells (CTL) represent the major defense mechanism against the spread
      of virus infection. It is believed that the pore-forming protein, perforin,
      facilitates the entry of a series of serine proteases (particularly granzyme B)
      into the target cell which ultimately leads to DNA fragmentation and apoptosis.
      We demonstrate here that during CTL-mediated cytolysis the catalytic subunit of
      DNA-dependent protein kinase (DNA-PKcs), an enzyme implicated in the repair of
      double strand breaks in DNA, is specifically cleaved by an interleukin (IL)-1
      beta-converting enzyme (ICE)-like protease. A serine protease inhibitor, 3,4
      dichloroisocoumarin (DCl), which is known to block granzyme B activity, inhibited
      CTL-induced apoptosis and prevented the degradation of DNA-PKcs in cells but
      failed to prevent the degradation of purified DNA-PKcs by CTL extracts. However,
      Tyr-Val-Ala-Asp-CH2Cl (YVAD-CMK) and other cysteine protease inhibitors prevented
      the degradation of purified DNA-PKcs by CTL extracts. Furthermore, incubation of
      DNA-PKcs with granzyme B did not produce the same cleavage pattern observed in
      cells undergoing apoptosis and when this substrate was incubated with either CTL
      extracts or the ICE-like protease, CPP32. Sequence analysis revealed that the
      cleavage site in DNA-PKcs during CTL killing was the same as that when this
      substrate was exposed to CPP32. This study demonstrates for the first time that
      the cleavage of DNA-PKcs in this intact cell system is exclusively due to an ICE
      like protease.

PMID- 8760817
TI  - Selectins and neutrophil traffic: margination and Streptococcus pneumoniae
      induced emigration in murine lungs.
AB  - The roles of selectins in the pulmonary margination and emigration of neutrophils
      were investigated by using mice genetically deficient in both E- and P-selectins
      (E/P mutants) and/or by intravenous injections of fucoidin (inhibiting both L-
      and P-selectins). E/P mutants were neutrophilic (14.7 +/- 4.9 x 10(6) vs. 0.8 +/-
      0.1 x 10(6) neutrophils/ml). This neutrophilia was associated with increased
      margination of neutrophils within pulmonary capillaries (39.7 +/- 9.4 vs. 4.6 +/-
      1.1 neutrophil profiles per 100 red blood cell profiles) but no change in
      margination within noncapillary pulmonary microvessels. After intratracheal
      instillation of Streptococcus pneumoniae, lungs of E/P mutants displayed
      increased neutrophil emigration (564 +/- 92 vs. 116 +/- 19 neutrophils per 100
      alveolar profiles), edema (5.3 +/- 1.5 vs. 1.5 +/- 0.4 microliter/g body weight),
      and histologic evidence of lung injury compared with those in wild-type (WT).
      Fucoidin treatment did not affect neutrophil emigration during streptococcal
      pneumonia in WT or E/P mice. During pneumonia, the number of white blood cells
      (WBC) tethered to or spread upon the noncapillary vessel endothelium increased in
      both WT and E/P lungs. These are the first data demonstrating that neutrophil
      margination in uninfected pulmonary capillaries does not require E- and P
      selectins; that streptococcal pneumonia induces an E- and P-selectin-independent
      increase in WBC interactions with noncapillary endothelium; and that migration of
      neutrophils to alveoli can occur despite deficiency or inhibition of all of the
      known selectins.

PMID- 8760816
TI  - Molecular definition of distinct cytoskeletal structures involved in complement-
      and Fc receptor-mediated phagocytosis in macrophages.
AB  - It has long been known from the results of ultrastructural studies that
      complement- and immunoglobulin G (IgG)-opsonized particles are phagocytosed
      differently by macrophages (Kaplan. G. 1977. Scand. J. Immunol. 6:797-807).
      Complement-opsonized particles sink into the cell, whereas IgG-coated particles
      are engulfed by lamellipodia, which project from the cell surface. The molecular
      basis for these differences is unknown. We used indirect immunofluorescence and
      confocal microscopy to examine how cytoskeletal proteins associate with
      phagosomes containing complement-opsonized zymosan (COZ) particles or IgG beads
      in phorbol-myristateacetate-treated peritoneal macrophages. During ingestion of
      COZ, punctate structures rich in F-actin, vinculin, alpha-actinin, paxillin, and
      phosphotyrosine-containing proteins are distributed over the phagosome surface.
      These foci are detected beneath bound COZ within 30 s of warming the cells to 37
      degrees C, and their formation requires active protein kinase C. By contrast,
      during Fc receptor-mediated phagocytosis, all proteins examined were uniformly
      distributed on or near the phagosome surface. Moreover, ingestion of IgG beads
      was blocked by tyrosine kinase inhibitors, whereas phagocytosis of COZ was not.
      Thus, the signals required for particle ingestion, and the arrangement of
      cytoskeletal proteins on the phagosome surface, vary depending upon which
      phagocytic receptor is engaged. Moreover, complement receptor (CR)-mediated
      internalization required intact microtubules and was accompanied by the
      accumulation of vesicles beneath the forming phagosome, suggesting that membrane
      trafficking plays a key role in CR-mediated phagocytosis.

PMID- 8760818
TI  - Identification of epitope mimics recognized by CTL reactive to the
      melanoma/melanocyte-derived peptide MART-1(27-35).
AB  - CTL reactivity to the epitope MART-1(27-35), of the melanoma (self) antigen MART
      1/melan A is frequently observed in tumor-infiltrating lymphocytes and may be
      readily elicited from the peripheral blood of melanoma patients that express HLA
      A*0201. Available data suggest that these observations contrast with those made
      for other HLA-A*0201-presented melanoma self antigens regarding the regularity of
      observed CTL responses. Based on preliminary findings, we hypothesized that the
      CTL response to MART-1 might be augmented in part by T cell encounters with
      peptides derived from sources other than MART-1, which show sequence similarity
      to MART-1(27-35). To test this idea, a protein database search for potential MART
      1 epitope mimics was done using criteria developed from analyses of effector
      recognition of singly-substituted peptide analogues of MART-1(27-35). Synthetic
      peptides were made for a portion of the sequences retrieved; 12/40 peptides
      tested were able to sensitize target cells for lysis by one or more anti-MART-1
      effectors. The peptides recognized correspond to sequences occurring in a variety
      of proteins of viral, bacterial, and human (self) origin. One peptide derives
      from glycoprotein C of the common pathogen HSV-1; cells infected with recombinant
      vaccinia virus encoding native glycoprotein C were lysed by anti-MART-1
      effectors. Our results overall indicate that sequences conforming to the A2.1
      binding motif and possessing features essential to recognition by anti-MART-1 CTL
      occur frequently in proteins. These findings further suggest that T cells might
      encounter a variety of such sequences in vivo, and that epitope mimicry may play
      a role in modulating the CTL response to MART-1(27-35).

PMID- 8760819
TI  - The characteristic site-specific reactivation phenotypes of HSV-1 and HSV-2
      depend upon the latency-associated transcript region.
AB  - After replication at sites of initial inoculation, herpes simplex virus type 1
      and 2 (HSV-1 and HSV-2) establish lifelong latent infections of the sensory and
      autonomic neurons of the ganglia serving those sites. Periodically, the virus
      reactivates from these neurons, and travels centripetally along the neuronal axon
      to cause recurrent epithelial infection. The major clinically observed difference
      between infections with herpes simplex virus type 1 and type 2 is the anatomic
      site specificity of recurrence. HSV-1 reactivates most efficiently and frequently
      from trigeminal ganglia, causing recurrent ocular and oral-facial lesions, while
      HSV-2 reactivates primarily from sacral ganglia causing recurrent genital
      lesions. An intertypic recombinant virus was constructed and evaluated in animal
      models of recurrent ocular and genital herpes. Substitution of a 2.8-kbp region
      from the HSV-1 latency-associated transcript (LAT) for native HSV-2 sequences
      caused HSV-2 to reactivate with an HSV-1 phenotype in both animal models. The HSV
      2 phenotype was restored by replacing the mutated sequences with wild-type HSV-2
      LAT-region sequences. These sequences or their products must act specifically in
      the cellular environments of trigeminal and sacral neurons to promote the
      reactivation patterns characteristic of each virus.

PMID- 8760820
TI  - Streptococcal cysteine proteinase releases kinins: a virulence mechanism.
AB  - Previous work has indicated a crucial role for the extracellular cysteine
      proteinase of Streptococcus pyogenes in the pathogenicity and virulence of this
      important human pathogen. Here we find that the purified streptococcal cysteine
      proteinase releases biologically active kinins from their purified precursor
      protein, H-kininogen, in vitro, and from kininogens present in the human plasma,
      ex vivo. Kinin liberation in the plasma is due to the direct action of the
      streptococcal proteinase on the kininogens, and does not involve the previous
      activation of plasma prekallikrein, the physiological plasma kininogenase. Judged
      from the amount of released plasma kinins the bacterial proteinase is highly
      efficient in its action. This is also the case in vivo. Injection of the purified
      cysteine proteinase into the peritoneal cavity of mice resulted in a progressive
      cleavage of plasma kininogens and the concomitant release of kinins over a period
      of 5 h. No kininogen degradation was seen in mice when the cysteine proteinase
      was inactivated by the specific inhibitor, Z-Leu-Val-Gly-CHN2, before
      administration. Intraperitoneal administration into mice of living S. pyogenes
      bacteria producing the cysteine proteinase induced a rapid breakdown of
      endogenous plasma kininogens and release of kinins. Kinins are hypotensive, they
      increase vascular permeability, contract smooth muscle, and induce fever and
      pain. The release of kinins by the cysteine proteinase of S. pyogenes could
      therefore represent an important and previously unknown virulence mechanism in S.
      pyogenes infections.

PMID- 8760821
TI  - CD27 cooperates with the pre-T cell receptor in the regulation of murine T cell
      development.
AB  - CD27 is a lymphocyte-specific member of the TNF receptor family and has a TNF
      related transmembrane ligand, CD70. The CD27/CD70 receptor-ligand pair cooperates
      with the TCR in the regulation of the peripheral T cell response. The study
      presented here reveals that CD27 may play a similar role in thymic pre-T cell
      development. We have previously cloned the cDNA encoding murine CD27, prepared
      specific mAbs and observed that murine CD27 is expressed on virtually all
      thymocytes, with the exception of a subpopulation of CD4-8- precursor T cells. It
      is shown here that induction of murine CD27 expression occurs at the transition
      from the CD4-8-25+ to the CD4-8-25- precursor T cell stage and is regulated by
      the pre-TCR. Therefore, we investigated whether CD27 contributes to pre-TCR
      mediated thymocyte development. Pre-TCR function was mimicked by the induction of
      CD3 signaling in thymocytes of recombination activating gene (RAG)-deficient
      mice. This in vivo anti-CD3 epsilon mAb treatment induces an about fifty fold
      numerical expansion of CD4-8-25+ thymocytes and their differentiation to the
      CD4+8+25- stage. Co-injection of anti-CD27 mAb inhibited the CD3-mediated
      expansion and differentiation of the CD4-8-25+ precursor population. Also,
      injection of anti-CD27 mAb in TCR alpha-/- mutant mice led to a reduction in the
      absolute number of CD4+8+25- thymocytes. We present evidence that in these in
      vivo systems, anti-CD27 mAb inhibits CD27-ligand interaction. Therefore, we
      conclude that CD27 may contribute to normal murine T cell development by
      synergizing with the pre-TCR-mediated signal.

PMID- 8760822
TI  - c-kit+ stem cells and thymocyte precursors in the livers of adult mice.
AB  - Livers of the adult mice contain c-kit+ stem cells that can reconstitute
      thymocytes, multiple lineage cells, and bone marrow (BM) stem cells. Transfer of
      1 x 10(7) hepatic mononuclear cells (MNC) and 5 x 10(4) hepatic c-kit+ cells of
      BALB/c mice induced DP thymocytes within a week in four Gy-irradiated CB17/-SCID
      mice, but 2 wk were required for BM cells or BM c-kit+ cells to produce DP
      thymocytes. Moreover, B cell-depleted BM cells or liver MNC of SCID mice that had
      been rescued by hepatic MNC of BALB/c mice again reconstituted thymus and B cells
      of other irradiated SCID mice. CD3- IL-2R beta- populations of both BM cells and
      hepatic MNC of C57BL/6 (B6) mice could generate T cells with intermediate TCR
      (mostly NK1.1-) in the liver of irradiated B6 SCID mice before thymic
      reconstitution (extrathymic T cells). Furthermore, transfer of liver c-kit+ cells
      of B6-Ly 5.1 mice into irradiated B6 SCID (Ly5.2) mice revealed that liver c-kit+
      cells can reconstitute myeloid and erythroid lineage cells. These results
      strongly suggest that the liver contains pluripotent stem cells and serves an
      important hematopoietic organ even into adulthood.

PMID- 8760823
TI  - CD34+ hematopoietic progenitors from human cord blood differentiate along two
      independent dendritic cell pathways in response to GM-CSF+TNF alpha.
AB  - Human dendritic cells (DC) can now be generated in vitro in large numbers by
      culturing CD34+ hematopoietic progenitors in presence of GM-CSF+TNF alpha for 12
      d. The present study demonstrates that cord blood CD34+ HPC indeed differentiate
      along two independent DC pathways. At early time points (day 5-7) during the
      culture, two subsets of DC precursors identified by the exclusive expression of
      CD1a and CD14 emerge independently. Both precursor subsets mature at day 12-14
      into DC with typical morphology and phenotype (CD80, CD83, CD86, CD58, high HLA
      class II). CD1a+ precursors give rise to cells characterized by the expression of
      Birbeck granules, the Lag antigen and E-cadherin, three markers specifically
      expressed on Langerhans cells in the epidermis. In contrast, the CD14+
      progenitors mature into CD1a+ DC lacking Birbeck granules, E-cadherin, and Lag
      antigen but expressing CD2, CD9, CD68, and the coagulation factor XIIIa described
      in dermal dendritic cells. The two mature DC were equally potent in stimulating
      allogeneic CD45RA+ naive T cells. Interestingly, the CD14+ precursors, but not
      the CD1a+ precursors, represent bipotent cells that can be induced to
      differentiate, in response to M-CSF, into macrophage-like cells, lacking
      accessory function for T cells. Altogether, these results demonstrate that
      different pathways of DC development exist: the Langerhans cells and the CD14(+)
      derived DC related to dermal DC or circulating blood DC. The physiological
      relevance of these two pathways of DC development is discussed with regard to
      their potential in vivo counterparts.

PMID- 8760824
TI  - Role of appendix in the development of inflammatory bowel disease in TCR-alpha
      mutant mice.
AB  - T cell receptor-alpha mutant mice (TCR-alpha-/-), created by gene targeting of
      the TCR-alpha gene in embryonic stem cells, spontaneously develop inflammatory
      bowel disease (IBD) resembling human ulcerative colitis. Since gut-associated
      lymphoid tissue is likely to play an important role in the development of chronic
      intestinal inflammation, we examined the changes in the appendix lymphoid
      follicle (ALF) and Peyer's patches (PP) in these mice. We found the structure of
      the ALF to be remarkably similar to that of the PP in the small intestine; in
      both instances, lymphoid follicles covered by surface epithelium (dome-formation)
      were found. The amount of proliferation in the lymphoid follicles of the appendix
      estimated by in vivo incorporation of 5-bromo-2'deoxyuridine was more than two
      times that of PP in TCR-alpha-/- mice. ELISPOT assay showed an increase of IgA,
      IgG1, and IgG2a, but not IgM-secreting B cells in ALF of TCR-alpha-/- mice
      compared to TCR-alpha+/- control mice. Furthermore, TCR-alpha-/- mice revealed an
      increase of autoantibody-producing B cells against the cytoskeletal protein
      tropomyosin in ALF as compared to PP. When TCR-alpha-/- mice underwent
      appendectomy at a young age (3-5 wk), the number of mesenteric lymph nodes cells
      at 6-7 mo were markedly less than in the sham-operated TCR-alpha-/- mice.
      Furthermore, appendectomy at 1 mo of age suppressed the development of IBD, with
      only 3.3% of these mice developing IBD in the 6-7-mo period of observation. In
      contrast, approximately 80% of controls, including the sham-operated TCR-alpha-/-
      mice, developed IBD during this period. These results suggest that ALF, rather
      than PP, is the priming site of cells involved in the disease process and plays
      an important role in the development of IBD in TCR-alpha-/- mice.

PMID- 8760825
TI  - Functional role of interleukin 1 beta (IL-1 beta) in IL-1 beta-converting enzyme
      mediated apoptosis.
AB  - Prointerleukin-1 beta (pro-IL-1 beta) is the only known physiologic substrate of
      the interleukin-1 beta (IL-1 beta)-converting enzyme (ICE), the founding member
      of the ICE/ced-3 cell death gene family. Since secreted mature IL-1 beta has been
      detected after apoptosis, we investigated whether this cytokine, when produced
      endogenously, plays a role in cell death. We found that hypoxia-induced apoptosis
      can be inhibited by either the IL-1 receptor antagonist (IL-1Ra) or by
      neutralizing antibodies to IL-1 or to its type 1 receptor. IL-1Ra also inhibits
      apoptosis induced by trophic factor deprivation in primary neurons, as well as by
      tumor necrosis factor alpha in fibroblasts. In addition, during the G1/S phase
      arrest, mature IL-1 beta induces apoptosis through a pathway independent of CrmA
      sensitive gene activity. We also demonstrate that Ice, when expressed in COS
      cells, requires the coexpression of pro-IL-1 beta for the induction of apoptosis,
      which is inhibited by IL-1Ra. Interestingly, we found that mature IL-1 beta has
      antiapoptotic activity when added exogenously before the onset of hypoxia, which
      we found is caused in part by its ability to downregulate the IL-1 receptor. Our
      findings demonstrate that pro-IL-1 beta is a substrate of ICE relevant to cell
      death, and depending on the temporal cellular commitment to apoptosis, mature IL
      1 beta may function as a positive or negative mediator of cell death.

PMID- 8760826
TI  - Function of the p55 tumor necrosis factor receptor "death domain" mediated by
      phosphatidylcholine-specific phospholipase C.
AB  - Tumor necrosis factor (TNF) is a pleiotropic mediator of inflammation that has
      been implicated in the pathogenesis of devastating clinical syndromes including
      septic shock. We have investigated the role of a TNF-responsive
      phosphatidylcholine-specific phospholipase C (PC-PLC) for the cytotoxic and
      proinflammatory activity of TNF. We show here that the cytotoxicity signaled for
      by the so-called "death domain" of the p55 TNF receptor is associated with the
      activation of PC-PLC. The xanthogenate tricyclodecan-9-yl (D609), a specific and
      selective inhibitor of PC-PLC, blocked the cytotoxic action of TNF on L929 and
      Wehi164 cells. In vivo, D609 prevented both adhesion molecule expression in the
      pulmonary vasculature and the accompanying leukocyte infiltration in TNF-treated
      mice. More strikingly, D609 protects BALB/c mice from lethal shock induced either
      by TNF, lipopolysaccharide, or staphylococcal enterotoxin B. Together these
      findings imply PC-PLC as an important mediator of the pathogenic action of TNF,
      suggesting that PC-PLC may serve as a novel target for anti-inflammatory TNF
      antagonists.

PMID- 8760827
TI  - The inter-locus recombinant HLA-B*4601 has high selectivity in peptide binding
      and functions characteristic of HLA-C.
AB  - The vast majority of new human HLA class I alleles are formed by conversions
      between existing alleles of the same locus. A notable exception to this rule is
      HLA-B*4601 formed by replacement of residues 66-76 of the alpha 1 helix of B*1501
      by the homologous segment of Cw*0102. This inter-locus recombination, which
      brings together characteristic elements of HLA-B and HLA-C structure, is shown
      here to influence function dramatically. Naturally processed peptides bound by
      B*4601 are distinct from those of its parental allotypes B*1501 and Cw*0102 and
      dominated by three high abundance peptides. Such increased peptide selectivity by
      B*4601 is unique among HLA-A,B,C allotypes. For other aspects of function,
      presence of the small segment of HLA-C-derived sequence in an otherwise HLA-B
      framework converts B*4601 to an HLA-C-like molecule. Alloreactive cytotoxic T
      lymphocytes (CTL), natural killer (NK) cells, and cellular glycosidases all
      recognize B*4601 as though it were an HLA-C allotype. These unusual properties
      are those of an allotype which has frequencies as high as 20% in south east Asian
      populations and is associated with predisposition to autoimmune diseases and
      nasopharyngeal carcinoma.

PMID- 8760828
TI  - High level IL-12 production by murine dendritic cells: upregulation via MHC class
      II and CD40 molecules and downregulation by IL-4 and IL-10.
AB  - We have shown previously that dendritic cells (DC) produce IL-12 upon interaction
      with CD4+ T cells. Here we ask how this IL-12 production is induced and
      regulated. Quantitative PCR and in situ hybridization for IL-12 p40 and an ELISA
      specific for the p70 heterodimer were used to determine IL-12 production. We
      demonstrate that ligation of either CD40 or MHC class II molecules independently
      trigger IL-12 production in DC, and that IL-12 production is downregulated by IL
      4 and IL-10. The levels of bioactive IL-12 that can be released by triggering
      with an anti-CD40 mAb or with a T cell hybridoma are high (range 260-4700 pg/ml
      from 1 X 10(6) DC in 72 h). The CD40-mediated pathway indicates that IL-12
      production is induced in DC upon interaction with activated, CD40 ligand
      expressing helper T cells, even in the absence of cognate antigen recognition.
      Side-by-side comparison of IL-12 production, and blocking experiments employing
      an anti-CD40 ligand mAb, suggest that the CD40-mediated pathway is quantitatively
      more significant than induction via the MHC class II molecule. The importance of
      the CD40/CD40 ligand interaction for IL-12 induction in DC likely contributes to
      the recent finding that mice lacking the CD40 ligand are impaired in mounting Th1
      type cell-mediated immune responses.

PMID- 8760829
TI  - Ligation of CD40 on dendritic cells triggers production of high levels of
      interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC
      activation.
AB  - We investigated the possibility that T helper cells might enhance the stimulatory
      function of dendritic cells (DCs). We found that ligation of CD40 by CD40L
      triggers the production of extremely high levels of bioactive IL-12. Other
      stimuli such as microbial agents, TNF-alpha or LPS are much less effective or not
      at all. In addition, CD40L is the most potent stimulus in upregulating the
      expression of ICAM-1, CD80, and CD86 molecules on DCs. These effects of CD40
      ligation result in an increased capacity of DCs to trigger proliferative
      responses and IFN-gamma production by T cells. These findings reveal a new role
      for CD40-CD40L interaction in regulating DC function and are relevant to design
      therapeutic strategies using cultured DCs.

PMID- 8760830
TI  - A role for CD9 molecules in T cell activation.
AB  - Costimulation mediated by the CD28 molecule plays an important role in optimal
      activation of T cells. However, CD28-deficient mice can mount effective T cell
      dependent immune responses, suggesting the existence of other costimulatory
      systems. In a search for other costimulatory molecules on T cells, we have
      developed a monoclonal antibody (mAb) that can costimulate T cells in the absence
      of antigen-presenting cells (APC). The molecule recognized by this mAb, 9D3, was
      found to be expressed on almost all mature T cells and to be a protein of
      approximately 24 kD molecular mass. By expression cloning, this molecule was
      identified as CD9, 9D3 (anti-CD9) synergized with suboptimal doses of anti-CD3
      mAb in inducing proliferation by virgin T cells. Costimulation was induced by
      independent ligation of CD3 and CD9, suggesting that colocalization of these two
      molecules is not required for T cell activation. The costimulation by anti-CD9
      was as potent as that by anti-CD28. Moreover, anti-CD9 costimulated in a CD28
      independent way because anti-CD9 equally costimulated T cells from the CD28
      deficient as well as wild-type mice. Thus, these results indicate that CD9 serves
      as a molecule on T cells that can deliver a potent CD28-independent costimulatory
      signal.

PMID- 8760831
TI  - Identification of CD8 as a peanut agglutinin (PNA) receptor molecule on immature
      thymocytes.
AB  - Differentiation of most T lymphocytes occurs within the thymus and is
      characterized by variable expression of CD4/CD8 coreceptor molecules, increased
      surface density of T cell antigen receptor (TCR) alpha beta proteins, and
      decreased expression of glycan chains recognized by the galactose-specific lectin
      peanut agglutinin (PNA). Although appreciated for several decades that PNA
      agglutination is useful for the physical separation of immature and mature
      thymocyte sub-populations, the identity of specific PNA-binding glycoproteins
      expressed on immature thymocytes remains to be determined. In the current report,
      we studied the expression of PNA-specific glycans on immature and mature T cells
      and used lectin affinity chromatography and immunoprecipitation techniques to
      characterize PNA-binding glycoproteins on thymocytes. Our data demonstrate that
      PNA-specific glycans are localized on a relatively small subset of thymocyte
      surface proteins, several of which were specifically identified, including CD43,
      CD45, and suprisingly, CD8 molecules. CD8 alpha and CD8 alpha' proteins bound to
      PNA in the absence of CD8 beta expression showing that O-glycans on CD8 beta
      glycoproteins are not necessary for PNA binding and that glycosylation of CD8
      alpha and CD8 alpha' proteins proceeds effectively in the absence of CD8 beta.
      Finally, we demonstrate that PNA binding of CD8 is developmentally regulated by
      sialic acid addition as CD8 proteins from mature T cells bound to PNA only after
      sialidase treatment. These studies identify CD8 as a PNA receptor molecule on
      immature thymocytes and show that PNA binding of CD8 on immature and mature T
      cells is developmentally regulated by sialic acid modification.

PMID- 8760832
TI  - Selective cleavage of nuclear autoantigens during CD95 (Fas/APO-1)-mediated T
      cell apoptosis.
AB  - Intracellular proteases appear to be important mediators of apoptosis. Substrates
      cleaved by proteases during apoptosis include nuclear autoantigens targeted in
      systemic autoimmune diseases. Using human autoantibodies as probes, we
      demonstrate here that T cell apoptosis mediated by CD95 (Fas/APO-1) is associated
      with substantial cleavage of a subset of nuclear autoantigens (7 of 33 examined).
      This subset included poly (ADP-ribose) polymerase, the 70-kD protein of the U1
      small nuclear ribonucleoprotein particle, lamin B, the nuclear mitotic apparatus
      protein NuMA, DNA topoisomerases I and II, and the RNA polymerase I upstream
      binding factor UBF. Several of the cleaved autoantigens are involved in ensuring
      the integrity and proper conformation of DNA in the nucleus through interactions
      with the nuclear matrix, suggesting the possibility that their cleavage may
      contribute to the collapse of nuclear structure during apoptosis. The relative
      cleavage kinetics indicated that the autoantigens were targeted at various times
      after induction of apoptosis, suggesting either differential accessibility or
      activation of distinct proteases during the cell death process. These data
      reinforce the hypothesis that apoptosis is accompanied by selective cleavage of
      key substrates and not by a generalized degradation of intracellular material.

PMID- 8760833
TI  - Early biochemical signals arise from low affinity TCR-ligand reactions at the
      cell-cell interface.
AB  - The kinetics of acid release by a mixture of T cells and antigen presenting cells
      were measured with a microphysiometer during a brief exposure to antigenic
      peptides. We find that some of the early biochemical events that lead to cellular
      proliferation cause a specific increase in the rate of acid release. The duration
      of this increase in acid release reflects the life-time of the peptide-MHC
      complexes. Peptides that form long-lived complexes produce a response that is
      stable for more than an hour. Serial TCR engagement is suggested by the
      observation that the amplitude of this stable response can be rapidly shifted up
      or down with additional agonist peptide or with antibodies that block T cell
      receptor binding. Cells briefly exposed to a peptide that forms short-lived
      peptide-MHC complexes produce a response that decays rapidly as peptide is washed
      away. A quantitative analysis of the kinetics of this decay in acidification
      demonstrates that intercellular TCR-ligand reactions are rapid, reversible, and
      of low apparent affinity with < 20% of peptide-MHC ligand bound to a TCR at any
      one time. These results demonstrate that the fraction of peptide-MHC ligands
      bound to TCRs at the cell-cell interface is no higher than anticipated from the
      affinities observed in solution for isolated TCRs and ligands.

PMID- 8760834
TI  - CTLA-4: a negative regulator of autoimmune disease.
AB  - CTLA-4, a CD28 homologue expressed on activated T cells, binds with high affinity
      to the CD28 ligands, B7-1 (CD80) and B7-2 (CD86). This study was designed to
      examine the role of CTLA-4 in regulating autoimmune disease. Murine relapsing
      remitting experimental autoimmune encephalomyelitis (R-EAE) is a demyelinating
      disease mediated by PLP139-151-specific CD4+ T cells in SJL/J mice. Anti-CTLA-4
      mAbs (or their F(ab) fragments) enhanced in vitro proliferation and pro
      inflammatory cytokine production by PLP139-151-primed lymph node cells. Addition
      of either reagent to in vitro activation cultures potentiated the ability of T
      cells to adoptively transfer disease to naive recipients. In vivo administration
      of anti-CTLA-4 mAb to recipients of PLP139-151-specific T cells resulted in
      accelerated and exacerbated disease. Finally, anti-CTLA-4 treatment of mice
      during disease remission resulted in the exacerbation of relapses. Collectively,
      these results suggest that CTLA-4 mediates the downregulation of ongoing immune
      responses and plays a major role in regulating autoimmunity.

PMID- 8760835
TI  - Regulation of T cell lymphokine production by killer cell inhibitory receptor
      recognition of self HLA class I alleles.
AB  - The killer cell inhibitory receptors (KIRs) are surface glycoproteins expressed
      by natural killer (NK) and T cells that specifically recognize defined groups of
      polymorphic human histocompatibility leukocyte antigen (HLA) class I molecules.
      Interactions between KIRs on NK or T cells and major histocompatibility complex
      (MHC) class I molecules on potential target cells inhibit cell-mediated
      cytotoxicity, presumably by delivering a negative signal preventing lymphocyte
      activation. In this study we examined whether KIRs also regulate cytokine
      production induced in response to T cell receptor-dependent T cell activation.
      CD4+ and CD8+ T cell clones were stimulated by bacterial superantigens in the
      presence or absence of monoclonal antibodies (mAbs) against the KIR NKB1 or MHC
      class I molecules, and production of tumor necrosis factor alpha and interferon
      gamma was evaluated. When bacterial superantigen was presented by an autologous
      antigen-presenting cell (APC) to a KIR+ T cell clone, cytokine production was
      always enhanced in the presence of anti-MHC class I mAb. Similarly, anti-KIR mAb
      also augmented cytokine production, provided that the APC expressed a HLA class I
      allele recognized by the KIR. These results suggest that recognition of
      autologous MHC class I molecules by KIR+ T cells provides a regulatory mechanism
      acting to modulate the potency of their responses to antigenic challenge.

PMID- 8760836
TI  - Righting the wrong paradigm.

PMID- 8760837
TI  - Progressive mandibular retrusion-idiopathic condylar resorption. Part II.

PMID- 8760838
TI  - Video cephalometric diagnosis (VCD): a new concept in treatment planning?

PMID- 8760839
TI  - Orthodontic treatment of an open bite patient with oral-facial-digital syndrome.
AB  - A case of oral-facial-digital syndrome was treated orthodontically.
      Characteristics of this case were mandibular protrusion with open bite. Occlusal
      stability after correction of this malocclusion was achieved with the uprighting
      of the posterior teeth, surgical reduction of the enlarged tonsils and highly
      attached tongue frenum, and oral functional training.

PMID- 8760840
TI  - Active vertical corrector treatment--long-term follow-up of anterior open bite
      treated by the intrusion of posterior teeth.

PMID- 8760841
TI  - Patient with severe skeletal Class III malocclusion and severe open bite treated
      by orthodontics and orthognathic surgery--a case report.

PMID- 8760842
TI  - An American Board of Orthodontics case report: an adult nonsurgical patient whose
      treatment required combined dental disciplines.
AB  - This is a case report of a 27-year-old, white woman who had a Class II, Division
      2 malocclusion with 100% overbite and mild skeletal mandibular retrognathia.
      Missing teeth were the maxillary right canine, second premolar, and second molar;
      the maxillary left canine and second molar; the mandibular left first premolar
      and second molar; the mandibular right first premolar and second molar. The
      maxillary first premolars were used as canines and the molars were in an Angle
      Class I relationship at the end of 31 months of treatment. Bonded lingual
      retainers were placed: a maxillary lateral incisor-to-lateral incisor, a
      mandibular canine-to-canine, and a maxillary Hawley retainer. Later, a fixed
      restoration to replace the maxillary right second premolar was completed.
      Included are 3-year posttreatment records.

PMID- 8760843
TI  - Diagnosis of macroglossia and indications for reduction glossectomy.
AB  - Macroglossia can create dentomusculoskeletal deformities, instability of
      orthodontic and orthognathic surgical procedures, and masticatory, speech, and
      airway problems. The cause of macroglossia must be clearly defined, and true
      macroglossia separated from pseudomacroglossia (displacement of the tongue
      created by anatomic factors other than tongue size alone). This article discusses
      the signs and symptoms of macroglossia, including the clinical and radiographic
      features, treatment techniques, as well as previously reported results. Cases are
      shown to illustrate the applicability of this technique.

PMID- 8760844
TI  - Bracket angulation as a function of its length in the canine distal movement.
AB  - The slot angulations that are built into currently manufactured brackets are the
      same as those recommended more than 20 years ago. Because of a continuous trend
      toward miniaturization, the bracket slot length has diminished considerably, fact
      that should have had an impact on the characteristics of the slot. This impact
      has not yet taken place. A decrease in the overall bracket size and the
      shortening of the slot length invite unaccounted tooth rotation, which happens
      when an attempt is made to adhere to traditional angulations. If only a pure
      translation of a tooth is wanted, such a rotation becomes undesirable. To reduce
      its action, power arms are used. Unfortunately, these do not solve the problem.
      Indeed, to overcome this effect, a modification of the values of standard
      angulations is needed. To illustrate the point, maxillary canine retraction is
      considered, because it is both common and involves an already high bracket slot
      angulation. With standard solid mechanics and statics, new angulations are
      proposed as functions of the bracket slot length and arch wire rigidity. In
      addition, an estimation of the minimum useful size of the slot is made.

PMID- 8760845
TI  - Facial structure and functional findings in patients with progressive muscular
      dystrophy (Duchenne).
AB  - The investigation of 15 patients who have a progressive muscular dystrophy of the
      Duchenne type (PMD) shows the affection of various groups of muscles of the
      stomatognathic system, studied by means of electromyography and mechanical force
      measurements. We observed the following deviations in patients with PMD;
      transversal overdevelopment and sagittal shortening of the dental arch; reduction
      of overbite and overjet; sagittal underdevelopment of the cranial, maxillary and
      mandibular base; retrusion of incisors; concave profile; increase in bizygomatic
      width; and a difference in time between the attack on the musculi orbicularis
      oris and that on masticatory muscles. In our study, the activity of the jaw
      muscles diminished 2 years earlier compared with the perioral muscles. This, and
      also the enlargement of the hypotonic tongue, causes a transversal expansion of
      skull and dental arches. This expansion was strongly pronounced in the lower jaw;
      we invariably observed a posterior crossbite. In contrast to the transversal
      overdevelopment, we observed a sagittal underdevelopment of skeletal and dental
      parameters, as well as a retrusion of the incisors. The results of surface
      electromyography showed the affection of the masseter muscle in patients who had
      PMD. By means of the Fast-Fourier transformation, we observed a displacement of
      the median frequency as compared with the lower frequency range.

PMID- 8760846
TI  - Canine retraction: a comparison of two preadjusted bracket systems.
AB  - Before the 1970s, Begg and Edgewise appliances were the most commonly used
      appliances in orthodontics. With the introduction of preadjusted appliances, many
      have made claims of superiority. These claims are often unsubstantiated, as few,
      if any, have ever been tested in a controlled, prospective in vivo study. The
      purpose of this study was to compare the time required to retract canine teeth by
      using two different preadjusted bracket systems (Tip-Edge, TP Orthodontics,
      LaPorte, Ind., versus A-Company straight wire, Johnson and Johnson, San Diego,
      Calif.) in a human sample. Anchorage loss as a result of this movement was also
      evaluated. A sample of 12 patients was randomly selected from the new patient
      pool at the postgraduate orthodontic clinic of Montefiore Medical Center. All
      patients required the removal of first premolars in one or both arches as a part
      of their orthodontic treatment. The rate of retraction and anchorage loss were
      evaluated. Paired t tests were performed separately for the rates of retraction
      and anchorage loss. The mean rates of retraction were 1.88 mm per 3-week period
      and 1.63 mm per 3-week period for the Tip-Edge and A-Company brackets,
      respectively. There was no statistically significant difference in the rates (p >
      0.05). The mean anchorage loss was 1.71 mm for the Tip-Edge bracket, and 2.33 mm
      for the straight wire bracket. The difference in the amount of anchorage loss was
      inconclusive as the sample size was too small (power was 10%).

PMID- 8760847
TI  - Orthodontic concern among 11-year-old children and their parents compared with
      orthodontic treatment need assessed by index of orthodontic treatment need.
AB  - The aims of the study were to compare the opinions of both the children and the
      parents with an orthodontist's assessment of treatment need, to investigate the
      children's self-esteem, and parents' opinion of treatment results. The study
      group of 359 children (51% girls, 49% boys, mean age 10.6 years) and their
      parents were asked about their opinions in separate questionnaires. The self
      esteem of the children was measured by the global negative self-evaluation scale
      (GSE). An orthodontist assessed the children's dental casts with the index of
      Orthodontic Treatment Need (IOTN). Allocated to the dental health component (DHC)
      of IOTN, 53.2% children had very great to moderate need and 46.8% had little to
      no need. No sex difference was noted. The children's own assessments of the
      aesthetic component (AC) of IOTN were closer to the attractive end of the scale
      than the orthodontist's (p < 0.05). Desire for treatment was more frequent than
      dissatisfaction with children's occlusion (p < 0.001). The patients' orthodontic
      concern correlated significantly with both DHC and AC grades (p < 0.001). The
      children's GSE scores were not correlated to components of IOTN. For children
      with very great need, high self-esteem was related to orthodontic concern. The
      parents (90.8%) perceived dental esthetics to be equally important for girls and
      boys. Most parents (93.0%) thought the results of orthodontic treatment were
      good. The results indicate meaningful association between orthodontic concern and
      orthodontic treatment need assessed by IOTN. However, some patients with great
      need do not express orthodontic concern, whereas others with near ideal occlusion
      express concern.

PMID- 8760848
TI  - The curve of Spee revisited.
AB  - Through the use of a sophisticated measuring device and support computer
      technology, accurate arch circumferences were determined for 27 casts that
      exhibited moderate to severe curves of Spee. Arch circumference differences were
      subsequently obtained by comparing the measured arch length to a planar
      projection formed by the center of the incisal tips anteriorly and the
      distobuccal cusp tips of the second molars distally. A general relationship has
      been derived for the arch circumference differential, resulting from the
      elimination of the curve of Spee, versus the severity of the curve. The arch
      circumference reduction is considerably less than that found by earlier
      investigators, implying that the incisor protrusion often associated with
      leveling the curve of Spee is not primarily due to the aforementioned
      differential, but rather more directly due to the mechanics used in leveling the
      curve of Spee.

PMID- 8760849
TI  - Orthodontic services provided by general dentists.
AB  - A survey was mailed to a stratified random sample of general dentists to
      determine the amount and nature of orthodontic treatment provided by general
      practitioners to their patients. The response to the survey was 75%, a rate
      considered excellent for this type of mailing. A large majority of the responding
      dentists (76.3%) provide orthodontic services to their patients, with 19.3%
      providing comprehensive orthodontic treatment. The percentage of time spent
      providing orthodontic services varied greatly among general dentists, with only a
      very few practitioners spending more than 50%. The number of patients under
      active treatment also varied widely, with only about 17% of those practitioners
      providing comprehensive treatment having more than 50 patients. A comparison of
      the three groups of practitioners showed that there was no relationship between
      the level of orthodontic involvement (none, limited, comprehensive) and the
      number of miles from orthodontic specialist or the pattern of referrals to
      orthodontists. Extrapolation of data from this study to the results of other
      investigations led to an estimate of the relative percentage of treatment
      provided by orthodontic specialists, pediatric dentists, and general
      practitioners. Almost two thirds of orthodontic patients are treated by
      orthodontic specialists, with pediatric dentists treating less than 4%. Slightly
      less than one third of all orthodontic patients appear to receive treatment from
      general practitioners.

PMID- 8760850
TI  - A clinical evaluation of the effectiveness of a fluoride-releasing visible light
      activated bonding system to reduce demineralization around orthodontic brackets.
AB  - The presence of decalcification (white spots) after the removal of orthodontic
      appliances still remains a problem. A method to deliver fluoride to the area
      beneath and around the bonded attachments, independent of patient compliance,
      could be very helpful. Therefore special attention is being currently directed to
      the so-called "fluoride releasing bonding adhesives." A clinical trial was
      carried out to compare the effect of a visible light-cured fluoride-releasing (F
      releasing) material with a chemically cured nonfluoride resin on white spot
      formation during fixed orthodontic therapy. Fifty patients entered the trial, and
      762 brackets were bonded in a crossover design. Intraoral slides were taken
      before and after treatment and were evaluated for white spot formation.
      Statistical data analysis was carried out by means of a chi-square test. The
      results of this clinical study indicate that there was no significant difference
      between the decalcification rates for both types of adhesives. When the
      appearance of white spots was evaluated in an overall manner, there was
      significantly more upper than lower decalcification.

PMID- 8760852
TI  - Public or private?... that is the question.

PMID- 8760851
TI  - The effect of Herbst appliance treatment on the mandibular plane angle: a
      cephalometric roentgenographic study.
AB  - The purpose of this investigation was to assess the individual reaction pattern
      and the long-term effect of Herbst appliance treatment on the vertical jaw base
      relationship, as expressed by the mandibular plane angle (ML/NSL). In the
      evaluation special reference was given to the pretreatment vertical jaw base
      relationship (hypodivergent, normodivergent or hyperdivergent). Lateral head
      films of 80 patients (47 males and 33 females) from before, at start (when the
      appliance was placed) and at the end of Herbst treatment (when the appliance was
      removed) as well as 6 months and 4.5 to 5 years posttreatment were analyzed. The
      ML/NSL angle was on the average unaffected by Herbst therapy. Posttreatment, a
      continuous decrease in the ML/NSL took place. Male subjects showed a larger
      angular decrease than female subjects. However, a large interindividual variation
      existed. No statistically significant differences were found between
      hypodivergent, normodivergent, and hyperdivergent subjects.

PMID- 8760853
TI  - Expression of integrins in marmoset (Callithrix jacchus) ovary during
      folliculogenesis.
AB  - Integrins were localized immunohistochemically in marmoset ovaries (Callithrix
      jacchus) of defined cycle stages. With monoclonal antibodies against beta 1,
      alpha 2, alpha 3, and alpha 6 integrin subunits, immunoreactivity was
      predominantly found in ovaries of the follicular phase. In the luteal phase, non
      luteal cells, e.g. fibroblasts or endothelial cells expressed beta 1, alpha 2, or
      alpha 6 integrins. Immunostaining for the beta 1 subunit was strongest in
      granulosa cells of all growing follicles. Weak immunoreactivity was found in
      granulosa cells of atretic follicles, theca and interstitial cells. With the
      alpha 2 antibody, binding was evident in granulosa cells of many, but not of all,
      primordial and primary follicles. Expression of alpha 2 was also found in
      luteinized granulosa cells of tertiary follicles. In growing follicles,
      immunoreactivity of alpha 3 was restricted to granulosa cells of early secondary
      follicles. Within the epithelium, staining was almost exclusively found in
      granulosa cells bordering on the basal granulosa cell layer. In advanced stages
      of atresia, granulosa cells of antral follicles expressed the alpha 3 subunit.
      Integrin alpha 6 expression was evident in granulosa cells of all growing
      follicles but was absent during advanced stages of degeneration. The specific
      expression patterns of integrins suggest that these matrix receptors play a
      regulatory role during cyclic events in primate ovaries.

PMID- 8760854
TI  - Further observations on the early events that contribute to establishing the
      morphological pattern shown by the oestradiol suppressed testis.
AB  - The analysis of the morphological response of the seminiferous epithelium to
      hormone suppression after hypophysectomy has been widely used in the study of
      spermatogenesis. Unlike hypophysectomy, which causes a sharp fall in gonadotropin
      levels, oestradiol treatment, although mimicking its effects, leads to a partial
      and progressive hormone suppression. We have chosen this model in order to
      clarify further the early morphological response of the seminiferous epithelium
      to hormone suppression. For this purpose, adult male rats, injected daily from 1
      35 days with 50 micrograms oestradiol benzoate, were analyzed. Our observations
      showed that cell sloughing was the main cause of germ cell depletion in the
      oestradiol treated testis. After 17-18 days treatment, massive sloughing affected
      nearly all the germinal cells, but the correct synchronization of mitoses,
      meiosis and spermatid differentiation along the 14 stages of spermatogenesis was
      always well kept. Quantitative analysis showed that spermatogenic wave was well
      preserved in the oestradiol-treated animals and that sloughing was a stage
      independent phenomenon.

PMID- 8760855
TI  - The eggshell of Drosophila melanogaster: IX. Synthesis and morphogenesis of the
      innermost chorionic layer.
AB  - Synthesis and morphogenesis of the innermost chorionic layer (ICL) was
      investigated by conventional EM methods, freeze-fracturing, tissue culture in
      Robb's medium, and EM autoradiography. Both autoradiography and fine structure
      results have shown that ICL-components are secreted prior to other chorion
      proteins. Their secretion starts on stage 12a but the first layer of ICL
      molecules is visible at stage 12b. Its thickness is gradually increased during
      the next stages, taking first, a bilaminar form along with the inner endochorion.
      Later, at the end of choriogenesis, ICL is detached from the endochorion and
      takes its final thickness and configuration, consisting of a 3-dimensional
      crystal, about 40 nm thick. The isolated ICL in conditions of air water interface
      is a monolayer crystal 10 nm thick. Studies on chorion mutants showed that the
      amount of protein secreted by the follicle cells is independent to the process of
      crystallisation. These data show how a proteinaceous extracellular substance is
      gradually assembled to form a 3-D crystal and how it can be organised to perform
      functions such as the physiological resistance of the insect eggs against water
      loss or water uptake, whenever they are laid on substrates with extreme
      environmental conditions. These functions are performed by ICL in conjunction
      with the underlying wax layer.

PMID- 8760856
TI  - Morphological and immunohistochemical properties of primary long-term cultures of
      adult guinea-pig ventricular cardiomyocytes with peripheral cardiac neurons.
AB  - Long-term (2-12 weeks) cultures of adult guinea-pig ventricular myocytes,
      cocultured with neurons derived from stellate or intrinsic cardiac ganglia,
      retain their functional properties (Horackova et al., 1993, 1994, 1995). The
      present study was designed to investigate the morphological and immunochemical
      properties of such neurons and their associated cardiomyocytes. Cultured myocytes
      studied by means of phalloidin-rhodamine (for F-actin) and an antibody raised
      against myomes revealed parallel myofibrils with striations typical of rod-shaped
      cardiomyocytes, even while myocytes changed from cylindrical to flattened form as
      they established intercellular contacts. Microtubular networks, identified by
      alpha-tubulin DM1A antibody, were arrayed longitudinally in myofibrils, being
      especially prominent during the formation of intercellular contacts between
      myocytes. Histochemically identified adult peripheral autonomic neurons cultured
      alone or with myocytes displayed a variety of shapes. alpha-Tubulin staining was
      associated with the somata and neurites of various-shaped neurons whether
      cultured alone or with myocytes. Cultured neurons derived from stellate and
      intrinsic cardiac ganglia also exhibited staining for the general neuronal marker
      PGP 9.5 (protein gene product 9.5), and for specific markers of the following
      neurochemicals: tyrosine hydroxylase, acetylcholinesterase, choline
      acetyltransferase, neuropeptide Y, vasoactive intestinal peptide, calcitonin gene
      related peptide, bradykinin, oxytocin, and NADPH-diaphorase. These data indicate
      that: (a) adult ventricular myocytes cocultured with intrathoracic neurons retain
      the structural properties of adult myocytes found in vivo; (b) intrinsic cardiac
      and extrinsic intrathoracic neurons cultured alone or with cardiomyocytes display
      morphological characteristics similar to those of neurons studied in situ; (c)
      intrinsic cardiac and intrathoracic extracardiac neurons cultured alone or with
      cardiomyocytes display a variety of morphologies (unipolar, bipolar, and
      multipolar), larger and more multipolar neurons being present in cultures derived
      from stellate versus intrinsic cardiac ganglia; (d) such cultured neurons are
      associated with a number of neurochemicals, more than one chemical being
      associated with each neuron. This model presents an excellent opportunity to
      study the morphology of individual peripheral extracardiac and intracardiac
      neurons as well as their potential to produce various neurochemicals that are
      known to be involved in the neuromodulation of cardiomyocyte function.

PMID- 8760857
TI  - Intracellular insulin binding in Tetrahymena pyriformis.
AB  - Insulin, a classic vertebrate hormone, produces alterations in cellular
      metabolism and growth in the ciliate Tetrahymena pyriformis, as well as an
      increase in insulin binding upon subsequent exposure, a phenomenon known as
      hormonal imprinting. An antibody to a peptide corresponding to the alpha-subunit
      of the human insulin receptor (amino acid residues 657-670) was used to
      investigate the location and to partially characterize immunoreactive proteins in
      insulin-exposed and non-insulin-exposed cells (control). Confocal microscopy
      revealed immunofluorescent labeling of cilia, nuclei, vesicles and an oblong
      structure of unknown nature. Labeling of nuclei, mitochondria and ciliary
      microtubules was seen with immunoelectron microscopy. Labeling was absent on the
      cell and ciliary membranes by immunoelectron microscopy. Polyacrylamide gel
      electrophoresis revealed several differences in protein composition between
      control and insulin-exposed ciliary membrane extracts, especially in the 30-50
      kDa range. Immunoblotting revealed 2 reactive proteins in whole cell lysates but
      none were detected in ciliary membrane extracts or wheat germ agglutinin affinity
      column eluates of T. pyriformis whole cell preparations. Based on these findings
      it is unlikely that a cell surface structure similar to a mammalian insulin
      receptor exists in T. pyriformis.

PMID- 8760858
TI  - Distribution of anionic sites on microvascular endothelium of the chick
      chorioallantoic membrane.
AB  - It is generally accepted that luminal surfaces of adult microvascular endothelia
      present an anionic barrier that limits passage of anionic macromolecules. To
      assess the ontogeny of the barrier, temporal and spatial expression of
      endothelial anionic sites was evaluated in the chorioallantoic membrane of
      chicken embryos from days 4.5 to 18 of incubation. After an initial flush, the
      vessels were perfused with cationic ferritin (CF, 1.0 mg/ml in PBS) for 2 min.
      Following a second flush to remove unbound CF, the chick chorioallontoic
      membranes (CAMs) were fixed and processed for electron microscopy. Continuous CF
      binding was revealed on the luminal endothelium, the junctional clefts and the
      plasmalemmal vesicles from days 4.5 to 14. However, by day 18, anionic sites had
      become discontinuous. Prior perfusion with protamine sulfate abolished CF binding
      and facilitated native ferritin binding. Further ultrastructural evaluation,
      using peroxidase labeled LFA lectin, revealed sialic acid moieties in patches on
      the CAM endothelium. Thus, in early chick embryogenesis, the CAM endothelium
      displays a continuous pattern of luminal anionic sites comprised in part of
      sialic acid. As the CAM ages, endothelial anionic sites become reduced. That the
      expression of endothelial anionic domains remained constant despite changes in
      CAM microvascular permeability in early development (Rizzo et al., 1995a) serves
      to suggest a minimal role for anionic domains in the development of microvascular
      permselectivity during normal angiogenesis.

PMID- 8760859
TI  - A comparative study of perichondrial tissue in mammalian cartilages.
AB  - The general organization, cellular and extracellular components, and structural
      variation of perichondrium have been studied in different mammalian cartilages by
      polarized light and transmission electron microscopy. The overall structure is
      that of a dense connective tissue composed of variable numbers of thin,
      stratified, closely-packed lamellae, themselves composed of closely-matted
      collagen fibres running in the plane of the cartilage surface, but oriented at
      various angles to each other. Variations mainly concern the arrangement of the
      fibre bundles in the transition zones between perichondrial and cartilage
      matrices, and between perichondrium and surrounding tissues. Perichondrial cells
      have the characteristics of fibrocytes. A cambial layer of undifferentiated stem
      cells was never observed. A layer of 'perichondrial lining cells' with
      distinctive ultrastructural characteristics was observed in some cartilage units,
      which separates the perichondrium from the surrounding loose connective tissue.
      The ultrastructural results demonstrate that the cartilage and perichondrial
      extracellular matrices are distinct, and what have been designated perichondrial
      'transition' and 'proliferative' zones are in fact parts of the most superficial
      cartilage layer. Variations in perichondrial structure appear to correlate with
      diversity of cartilage function and we conclude that each cartilage unit plus
      perichondrium forms a tightly-integrated entity, best regarded as a unitary organ
      within the skeletal system.

PMID- 8760860
TI  - Indapamide accentuates cardiac chronotropic responses to epidermal growth factor
      in chick cardiomyocytes.
AB  - We have previously shown that indapamide [chloro-4-N-(methyl-2-indolinyl-1)
      sulfamoyal-3-benzamide] has a direct action on the heart to alter ion fluxes.
      This study sought to examine the potential interaction between indapamide and
      epidermal growth factor (EGF). Cardiomyocytes were prepared as primary culture
      from 7-day-old chick embryo hearts as aggregates that have a pattern of
      consistent spontaneous contraction. Indapamide enhanced the positive chronotropic
      response to EGF observed in chick embryonic ventricular myocyte aggregates while
      indapamide itself did not alter cardiac contractile frequency. Taken in
      conjunction with data that calcium channel blockade, inhibition of sodium entry
      or Na(+)-Ca2+ exchange in the cardiomyocyte opposes the positive chronotropic
      action of EGF on the cardiomyocyte, this study has identified an agent,
      indapamide, that accentuates the cardiomyocyte response to EGF.

PMID- 8760861
TI  - Estimate of epididymal transit time in the chimpanzee.
AB  - During their passage through the epididymis, sperm undergo functional changes
      which result in their maturation and in their ability to fertilize ova.
      Maturational changes effected during epididymal transport are attributable to
      sequential changes in various regions of the plasmalemma of the sperm head and
      flagella. These functional changes in the plasmalemma result, at least in part,
      from the sequential binding of proteins secreted by the epididymal epithelium
      into the epididymal lumen. An estimate of epididymal transit time is essential to
      such investigations. Time elapsed from a testicular arterial infusion of a single
      pulse of tritiated-thymidine to the release of 3H-labeled sperm into the lumen of
      the seminiferous tubule was about 39 days. Seminal fluid-free 3H-labeled sperm
      first appear in the ejaculate about 41 +/- 1 days post-infusion. Total transit
      time for 3H-labeled Sd2 sperm released into the tubular lumen to appear in the
      ejaculate is estimated as the difference between these values. Since total
      transit time is equal to the seminiferous tubule transit time plus the epididymal
      transit time, epididymal transit time constitutes some lesser portion of the
      total transit time of 2 +/- 1 days.

PMID- 8760863
TI  - Ultrastructural studies on paramyosin core filaments from native thick filaments
      in catch muscles.
AB  - Catch muscles of molluscs usually have thick filaments of about 100 nm in
      diameter. The filament is constructed of a paramyosin core filament and an outer
      layer of myosin molecules. Myosin molecules are situated on the paramyosin core
      filament towards both ends, and they consequently have polarity towards both
      ends. According to our observations on the paramyosin core filaments from the
      native thick filaments, they bear regular cross-striations on their surfaces of
      about 14.5 nm periodicity when incubated in a KCl solution for a short time. The
      periodic pattern is supposed to be representative of peculiar arrangements of
      paramyosin molecules in the core, but the periodic pattern disappeared during
      incubation in a solution of high concentration KCl for a prolonged time, and a
      'Bear-Selby net' pattern appeared substitutionally. These 'Bear-Selby net'
      patterns were conveniently divided into 3 types among 4 paramyosin core filaments
      from 4 'catch' muscles; the adductors of a pecten, an oyster and a clam, and the
      byssus retractor of a mussel. The 'Bear-Selby net' of an oyster resembled that of
      a pecten. Purified paramyosin crystals from the 4 muscles showed a common
      periodicity of about 72.5 nm. Electrophoresis with SDS of the 4 paramyosins on 6%
      polyacrylamide gels revealed molecular weights at 104 kD from a pecten, 105 kD
      from an oyster, 103 kD from a clam and 105 kD from a mussel.

PMID- 8760862
TI  - Somatostatin-14 and somatostatin-28 in chicken pancreatic islet D-cells.
AB  - Somatostatin (SST)-14 and mammalian (m) SST-28[1-14] immunoreactivities of
      chicken pancreatic islets were investigated by using light microscopic
      immunohistochemistry. Chicken D-cells in both A- and B-islets showed
      immunoreactivity to SST-14, but not to mSST-28[1-14]. The acid-extract from both
      splenic and ventral lobes of pancreas was fractionated by reverse-phase high
      performance liquid chromatography, and the SST-like immunoreactivity was measured
      in the radioimmunoassay using anti-SST-14 serum. In both lobes, the SST-like
      immunoreactivity was detected in the fraction which corresponded to that of SST
      14 standard, but was not found in that of mSST-28 standard.
      Immunohistochemically, pancreatic endocrine D-cells of 1 amphibian, 4 reptiles
      and 12 birds showed the same immunostaining property as chicken D-cells. By
      contrast, both SST-14- and mSST-28[1-14]-immunoreactive D-cells were observed in
      the pancreatic islets of 16 mammals. From these results, we concluded that
      chicken islet D-cells contain only SST-14-like peptide, but not SST-28-like
      peptide, and that this phenomenon may be common to the avian species.

PMID- 8760864
TI  - Dietary antioxidants in disease prevention.

PMID- 8760865
TI  - Recent advances in Annonaceous acetogenins.

PMID- 8760866
TI  - Conservation patterns in angiosperm rDNA ITS2 sequences.
AB  - The two internal transcribed spacers (ITS1 and ITS2) of nuclear ribosomal DNA
      have become commonly exploited sources of informative variation for interspecific
      /intergeneric-level phylogenetic analyses among angiosperms and other eukaryotes.
      We present an alignment in which one-third to one-half of the ITS2 sequence is
      alignable above the family level in angiosperms and a phenetic analysis showing
      that ITS2 contains information sufficient to diagnose lineages at several
      hierarchical levels. Base compositional analysis shows that angiosperm ITS2 is
      inherently GC-rich, and that the proportion of T is much more variable than that
      for other bases. We propose a general model of angiosperm ITS2 secondary
      structure that shows common pairing relationships for most of the conserved
      sequence tracts. Variations in our secondary structure predictions for sequences
      from different taxa indicate that compensatory mutation is not limited to paired
      positions.

PMID- 8760867
TI  - Phosphorus 31 solid state NMR characterization of oligonucleotides covalently
      bound to a solid support.
AB  - 31P cross polarization (CP) magic angle spinning (MAS) nuclear magnetic resonance
      (NMR) spectra were acquired for various linear and branched di- and tri
      nucleotides attached to a controlled pore glass (CPG) solid support. The
      technique readily distinguishes the oxidation state of the phosphorus atom
      (phosphate versus phosphate), the presence or absence of a protecting group
      attached directly to phosphorus (cyanoethyl), and other large changes in the
      phosphorus chemistry (phosphate versus phosphorothioate). However, differences in
      configurational details remote from the phosphorus atom, such as the attachment
      position of the ribose sugar (2'5' versus 3'5'), or the particulars of the
      nucleotide bases (adenine versus uridine versus thymine), could not be resolved.
      When different stages of the oligonucleotide synthetic cycle were examined, 31P
      CPMAS NMR revealed that the cyanoethyl protecting group is removed during the
      course of chain assembly.

PMID- 8760868
TI  - Recruitment of damaged DNA to the nuclear matrix in hamster cells following
      ultraviolet irradiation.
AB  - We examined the relationship between the nuclear matrix and DNA in the
      dihydrofolate reductase domain following irradiation of Chinese hamster cells
      with UV light. The fraction of matrix-bound DNA increased in transcribed and non
      transcribed regions during a 3 h period after irradiation. However, no increase
      was observed with excision repair-deficient cells mutant for the ERCC1 gene. The
      major UV-induced lesion, the cyclobutane pyrimidine dimer, increased in frequency
      in the matrix-bound DNA 1 h after irradiation, in both transcribed and non
      transcribed regions, but decreased subsequently. This phenomenon was also lacking
      in excision repair-deficient cells. These data demonstrate that recruitment of
      lesion-containing DNA to the nuclear matrix occurs following UV irradiation and
      suggest that this recruitment is dependent upon nucleotide excision repair. This
      is consistent with the concept of a 'repair factory' residing on the nuclear
      matrix at which excision repair occurs.

PMID- 8760869
TI  - Transcriptional terminators of RNA polymerase II are associated with yeast
      replication origins.
AB  - The compact organization of the Saccharomyces cerevisiae genome necessitates that
      non-coding regulatory sequences reside in close proximity to one another. Here we
      show there is an intimate association between transcription terminators and DNA
      replication origins. Four replication origins were analyzed in a reporter gene
      assay that detects sequences that direct 3' end formation of mRNA transcripts.
      All four replication origins function as orientation-independent transcription
      terminators in this system, producing truncated polyadenylated mRNAs. Despite
      this close association, the cis-acting elements that confer replication origin
      function are genetically separable from those required for transcription
      termination. Several models are explored in an attempt to address how and why the
      signals specifying transcription termination and replication initiation overlap.

PMID- 8760870
TI  - Codon-reading specificity of an unmodified form of Escherichia coli tRNA1Ser in
      cell-free protein synthesis.
AB  - Unmodified tRNA molecules are useful for many purposes in cell-free protein
      biosynthesis, but there is little information about how the lack of tRNA post
      transcriptional modifications affects the coding specificity for synonymous
      codons. In the present study, we prepared an unmodified form of Escherichia coli
      tRNA1Ser, which originally has the cmo5UGA anticodon (cmo5U = uridine 5-oxyacetic
      acid) and recognizes the UCU, UCA and UCG codons. The codon specificity of the
      unmodified tRNA was tested in a cell-free protein synthesis directed by designed
      mRNAs under competition conditions with the parent tRNA1Ser. It was found that
      the unmodified tRNA with the UGA anti-codon recognizes the UCA codon nearly as
      efficiently as the modified tRNA. The unmodified tRNA recognized the UCU codon
      with low, but detectable efficiency, whereas no recognition of the UCC and UCG
      codons was detected. Therefore, the absence of modifications makes this tRNA more
      specific to the UCA codon by remarkably reducing the efficiencies of wobble
      reading of other synonymous codons, without a significant decrease in the UCA
      reading efficiency.

PMID- 8760871
TI  - Bi-directional gene switching with the tetracycline repressor and a novel
      tetracycline antagonist.
AB  - We have screened a panel of tetracycline (tc)-like compounds for their potential
      use with tc-repressor (tetR) based gene switches. The interaction between tc and
      tetR appears quite specific, as only tc itself and its close homologues anhydro
      tc and doxycycline strongly inhibited DNA binding. However, a single tc-like
      compound, GR33076X, increased DNA binding of the tetR-VP16 fusion protein, both
      in eukaryotic cells and in bacteria. We provide evidence that this antagonist of
      tetracycline is potentially useful for accelerated gene switching, especially in
      whole animals.

PMID- 8760872
TI  - Cell cycle-regulated repression of B-myb transcription: cooperation of an E2F
      site with a contiguous corepressor element.
AB  - B-myb belongs to a group of cell cycle genes whose transcription is repressed in
      G0/early G1 through a binding site for the transcription factor E2F. Here, we
      show that the B-myb repressor element is specifically recognised by heterodimers
      consisting of DP-1 and E2F-1, E2F-3 or E2F-4. Surprisingly, E2F-mediated
      repression is dependent on a contiguous corepressor element that resembles the
      CHR previously established as a corepressor of the CDE in cell cycle genes
      derepressed in S/G2, such as cyclin A, cdc2 and cdc25C. A factor binding to the B
      myb CHR was identified in fractionated HeLa nuclear extract and found to interact
      with the minor groove, as previously shown by in vivo footprinting for the cyclin
      A CHR. The B-myb and cdc25C CHRs are related with respect to protein binding but
      are functionally clearly distinct. Our results support a model where both E2F-
      and CDE-mediated repression, acting at different stages in the cell cycle, are
      dependent on promoter-specific CHR elements.

PMID- 8760873
TI  - Minor groove hydration of DNA in aqueous solution: sequence-dependent next
      neighbor effect of the hydration lifetimes in d(TTAA)2 segments measured by NMR
      spectroscopy.
AB  - The hydration in the minor groove of double stranded DNA fragments containing the
      sequences 5'-dTTAAT, 5'-dTTAAC, 5'-dTTAAA and 5'-dTTAAG was investigated by
      studying the decanucleotide duplex d(GCATTAATGC)2 and the singly cross-linked
      decameric duplexes 5'-d(GCATTAACGC)-3'-linker-5'-d(GCGTTAATGC)-3' and 5'
      d(GCCTTAAAGC)-3'-linker-5'-d(GCTTTAAGGC)-3' by NMR spectroscopy. The linker
      employed consisted of six ethyleneglycol units. The hydration water was detected
      by NOEs between water and DNA protons in NOESY and ROESY spectra. NOE-NOESY and
      ROE-NOESY experiments were used to filter out intense exchange cross-peaks and to
      observe water-DNA NOEs with sugar 1' protons. Positive NOESY cross-peaks
      corresponding to residence times longer than approximately 0.5 ns were observed
      for 2H resonances of the central adenine residues in the duplex containing the
      sequences 5'-dTTAAT and 5'-dTTAAC, but not in the duplex containing the sequences
      5'-dTTAAA and 5'-dTTAAG. In all nucleotide sequences studied here, the hydration
      water in the minor groove is significantly more mobile at both ends of the AT
      rich inner segments, as indicated by very weak or negative water-A 2H NOESY cross
      peaks. No positive NOESY cross-peaks were detected with the G 1'H and C 1'H
      resonances, indicating that the minor groove hydration water near GC base pairs
      is kinetically less restrained than for AT-rich DNA segments. Kinetically
      stabilized minor groove hydration water was manifested by positive NOESY cross
      peaks with both A 2H and 1'H signals of the 5'-dTTAA segment in d(GCATTAATGC)2.
      More rigid hydration water was detected near T4 in d(GCATTAATGC)2 as compared
      with 5'-d(GCATTAACGC)-3'-linker-5'-d(GCGTTAATGC)-3', although the sequences
      differ only in a single base pair. This illustrates the high sensitivity of water
      DNA NOEs towards small conformational differences.

PMID- 8760874
TI  - Sequences involved in the dimerisation of human T cell leukaemia virus type-1
      RNA.
AB  - The formation of a genomic RNA dimer appears to be a critical step in the life
      cycle of all retroviruses. To investigate the site and nucleotide interactions
      involved in this process, a 531 bp DNA fragment encompassing sequences up- and
      downstream of the splice donor in human T cell leukaemia virus type 1 (HTLV-1)
      was inserted into a plasmid vector under the control of the SP6 promoter. RNA
      transcripts generated in vitro from this template formed dimers which could be
      dissociated by heating at 60-80 degrees C for 3 min. The physical properties of
      the dimeric RNA were not consistent with either Watson-Crick base pairing or
      guanine tetrad formation as being solely responsible for the interaction.
      Deletion mutagenesis identified a 32 nt sequence required for dimerisation.
      Computer modelling was carried out in order to identify putative RNA secondary
      structures within this essential region. A stem-loop structure was identified,
      the stem of which was conserved among different sequenced isolates of HTLV-1.
      This sequence also contains a 15 nt palindrome. We sought by disruptive and
      compensatory mutagenesis to define the possible roles of these two structures in
      dimer linkage.

PMID- 8760875
TI  - In vivo degradation of RNA polymerase II largest subunit triggered by alpha
      amanitin.
AB  - Alpha-Amanitin is a well-known specific inhibitor of RNA polymerase II (RNAPII)
      in vitro and in vivo. It is a cyclic octapeptide which binds with high affinity
      to the largest subunit of RNAPII, RPB1. We have found that in murine fibroblasts
      exposure to alpha-amanitin triggered degradation of the RPB1 subunit, while other
      RNAPII subunits, RPB5 and RPB8, remained almost unaffected. Transcriptional
      inhibition in alpha-amanitin-treated cells was slow and closely followed the
      disappearance of RPB1. The degradation rate of RPB1 was alpha-amanitin dose
      dependent and was not a consequence of transcriptional arrest. Alpha-Amanitin
      promoted degradation of RPB1 was prevented in cells exposed to actinomycin D,
      another transcriptional inhibitor. Epitope-tagged recombinant human RPB1 subunits
      were expressed in mouse fibroblasts. In cells exposed to alpha-amanitin the wild
      type recombinant subunit was degraded like the endogenous protein, but a mutated
      alpha-amanitin-resistant subunit remained unaffected. Hence, alpha-amanitin did
      not activate a proteolytic system, but instead its binding to mRPB1 likely
      represented a signal for degradation. Thus, in contrast to other inhibitors, such
      as actinomycin D or 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole, which
      reversibly act on transcription, inhibition by alpha-amanitin cannot be but an
      irreversible process because of the destruction of RNAPII.

PMID- 8760876
TI  - Characterization of a dominant negative mutant form of the HNF-4 orphan receptor.
AB  - The HNF-4 orphan receptor is a member of the nuclear receptor family of
      transcription factors and a major regulator of genes involved in carbohydrate and
      lipid metabolism. As an initial step in characterizing the role of HNF-4 in the
      regulation of metabolism, we have generated a dominant negative form of HNF-4 (DN
      HNF-4) that contains a defective DNA-binding domain. In gel mobility shift
      assays, DN-HNF-4 did not bind an oligonucleotide probe representing an essential
      HNF-4 binding site, C3P contained in the human apo CIII promoter, but did prevent
      the binding of two recombinant isoforms, HNF-4alpha1 and HNF-4alpha2, as well as
      naturally-occurring HNF-4. DN-HNF-4 had no effect on the binding of PPARgamma
      RXRalpha heterodimers to a PPAR response element. In transfected HepG2 cells, DN
      HNF-4 dramatically reduced constitutive transcriptional activity of the human apo
      CIII promoter and abolished the positive transcriptional activity caused by
      plasmids expressing either isoform of HNF-4. These results indicate that DN-HNF-4
      is a selective dominant negative mutant which forms defective heterodimers with
      wild-type HNF-4, thereby preventing DNA binding and subsequent transcriptional
      activation by HNF-4.

PMID- 8760877
TI  - Effects of oligonucleotide length, mismatches and mRNA levels on C-5 propyne
      modified antisense potency.
AB  - To understand the parameters required for designing potent and specific antisense
      C-5 propynyl-pyrimidine-2'-deoxyphosphorothioate-modified oligonucleotides (C-5
      propyne ONs), we have utilized a HeLa line that stably expresses luciferase under
      tight control of a tetracycline-responsive promoter. Using this sensitive and
      regulatable cell-based system we have identified five distinct antisense ONs
      targeting luciferase and have investigated the role that ON length, target
      mismatches, compound stability and intracellular RNA levels play in affecting
      antisense potency. We demonstrate that C-5 propyne ONs as short as 11 bases
      retained 66% of the potency demonstrated by the parent 15 base compound, that a
      one base internal mismatch between the antisense ON and the luciferase target
      reduced the potency of the antisense ON by 43% and two or more mismatches
      completely inactivated the antisense ON and that C-5 propyne ONs have a
      biologically active half-life in tissue culture of 35 h. In addition, by
      regulating the intracellular levels of the luciferase mRNA over 20-fold, we show
      that the potency of C-5 propyne ONs is unaffected by changes in the expression
      level of the target RNA. These data suggest that low and high copy messages can
      be targeted with equivalent potency using C-5 propyne ONs.

PMID- 8760878
TI  - Extrachromosomal, homologous expression of trypanothione reductase and its
      complementary mRNA in Trypanosoma cruzi.
AB  - Trypanothione reductase (TR), a flavoprotein oxidoreductase present in
      trypanosomatids but absent in human cells, is regarded as a potential target for
      the chemotherapy of several tropical parasitic diseases caused by trypanosomes
      and leishmanias. We investigated the possibility of modulating intracellular TR
      levels in Trypanosoma cruzi by generating transgenic lines that
      extrachromosomally overexpress either sense or antisense TR mRNA. Cells
      overexpressing the sense construct showed a 4-10-fold increase in levels of TR
      mRNA, protein and enzyme activity. In contrast, recombinant T.cruzi harbouring
      the antisense construct showed no significant difference in TR protein or
      catalytic activity when compared with control cells. Although increased levels of
      TR mRNA were detected in some of the antisense cells neither upregulation nor
      amplification of the endogenous trypanothione reductase gene (tryA) was observed.
      Instead, a proportion of plasmid molecules was found rearranged and, as a result,
      contained the tryA sequence in the sense orientation. Plasmid rescue experiments
      and sequence analysis of rearranged plasmids revealed that this specific gene
      inversion event was associated with the deletion of small regions of flanking
      DNA.

PMID- 8760879
TI  - TBP binds the transcriptionally inactive TA5 sequence but the resulting complex
      is not efficiently recognised by TFIIB and TFIIA.
AB  - The binding of TBP (TFIID) to the TATA box has been considered to direct promoter
      recognition and pre-initiation complex formation because it is the first event
      leading to basal transcription by RNA polymerase II. Here, we analyse the binding
      of yeast TBP to a consensus TATAAA box and two point mutations, TAAAAA (inactive)
      and TATATA (active). Despite the fact that the TAAAAA sequence does not support
      transcription in vitro, yeast TBP binds the three sequences showing, in this
      sense, only a limited sequence specificity. However, the TBP-TAAAAA complex
      cannot be recognised by other basal transcription factors, in particular by
      TFIIB. DNase I footprinting patterns of the TBP-TAAAAA complex are different from
      those observed in functional TBP-TATA box complexes, indicating that, most
      likely, it is a different spatial arrangement of the TBP-DNA complex that
      prevents formation of the TFIIB-TBP-TAAAAA complex, also seriously impairing
      entry of TFIIA to the complex. DNA deformability of the A/T-rich sequences
      appears to be an important determinant in the formation of a productive TBP-TATA
      complex. These results indicate that the transcriptional competence of A/T-rich
      sequences is determined not only by TBP binding, but also by the ability of other
      basal transcription factors to recognise the preformed TBP-DNA complexes.

PMID- 8760880
TI  - Participation of altered upstream stimulatory factor in the induction of rat heme
      oxygenase-1 by cadmium.
AB  - We have reported that an upstream stimulatory factor (USF) binding site is
      functional in transcription of the heme oxygenase-1 gene. In this study, we
      examined the role of USF in the induced state. By transient expression analyses
      with the chloramphenicol acetyl-transferase gene, we found that the USF binding
      site plays an important role in the induction of rat heme oxygenase-1 by cadmium,
      but not by hemin. To elucidate the role of USF, we prepared USF-rich nuclear
      extracts from control and cadmium-treated rat liver. On electrophoretic mobility
      shift assay using control nuclear proteins, one slowly migrating band was
      detected, whereas using nuclear proteins of cadmium-treated rat liver, two fast
      migrating bands were detected. The molecular masses of the two subunits of USF
      prepared from cadmium-treated rat liver were approximately 34 kDa as determined
      by UV cross-linking and subsequent SDS-PAGE, while the two subunits of native USF
      were 43 kDa and 44 kDa. DNase I footprinting analysis revealed that both the
      nuclear proteins bound to the same region including the USF binding site. We
      therefore suppose that cadmium causes some structural changes in the two proteins
      of USF and that the altered USF participates in the effective initiation of
      transcription of the rat heme oxygenase-1 gene.

PMID- 8760881
TI  - Oligo-2'-fluoro-2'-deoxynucleotide N3'-->P5' phosphoramidates: synthesis and
      properties.
AB  - Uniformly modified oligodeoxyribonucleotide N3'-->P5' phosphoramidates containing
      2'-fluoro-2'-deoxy-pyrimidine nucleosides were synthesized using an efficient
      interphase amidite transfer reaction. The 3'-amino group of solid phase-supported
      2'-fluoro-2'-deoxynucleoside was used as an acceptor and 5'-diisopropylamino
      phosphoramidite as a donor of a phosphoramidite group in the tetrazole-catalyzed
      exchange reaction. Subsequent oxidation with aqueous iodine resulted in formation
      of an internucleoside phosphoramidate diester. The prepared oligo-2'-fluoro
      nucleotide N3'-->P5' phosphoramidates form extremely stable duplexes with
      complementary nucleic acids: relative to isosequential phosphodiester oligomers,
      the melting temperature Tm of their duplexes with DNA or RNA was increased
      approximately 4 or 5 degrees C per modification respectively. Moreover, these
      compounds are highly resistant to enzymatic hydrolysis by snake venom
      phosphodiesterase and they are 4-5 times more stable in acidic media (pH 2.2-5.3)
      than the parent oligo-2'-deoxynucleotide N3'-->P5' phosphoramidates. The
      described properties of the oligo-2'-fluoronucleotide N3'-->P5' phosphoramidates
      suggest that they may have good potential for diagnostic and antisense
      therapeutic applications.

PMID- 8760882
TI  - Oligodeoxynucleotides containing C-7 propyne analogs of 7-deaza-2'-deoxyguanosine
      and 7-deaza-2'-deoxyadenosine.
AB  - The synthesis, hybridization properties and antisense activities of
      oligodeoxynucleotides (ODNs) containing 7-(1-propynyl)-7-deaza-2'-deoxyguanosine
      (pdG) and 7-(1-propynyl)-7-deaza-2'-deoxyadenosine (pdA) are described. The
      suitably protected nucleosides were synthesized and incorporated into ODNs.
      Thermal denaturation (Tm) of these ODNs hybridized to RNA demonstrates an
      increased stability relative to 7-unsubstituted deazapurine and unmodified ODN
      controls. Antisense inhibition by these ODNs was determined in a controlled
      microinjection assay and the results demonstrate that an ODN containing pdG is
      approximately 6 times more active than the unmodified ODN. 7-Propyne-7-deaza-2'
      deoxyguanosine is a promising lead analog for the development of antisense ODNs
      with increased potency.

PMID- 8760883
TI  - Sequence specific binding of chlamydial histone H1-like protein.
AB  - Chlamydia trachomatis is one of the few prokaryotic organisms known to contain
      proteins that bear homology to eukaryotic histone H1. Changes in macromolecular
      conformation of DNA mediated by the histone H1-like protein (Hc1) appear to
      regulate stage specific differentiation. We have developed a cross-linking
      immunoprecipitation protocol to examine in vivo protein-DNA interaction by immune
      precipitating chlamydial Hc1 cross linked to DNA. Our results strongly support
      the presence of sequence specific binding sites on the chlamydial plasmid and hc1
      gene upstream of its open reading frame. The preferential binding sites were
      mapped to 520 bp BamHI-XhoI and 547 bp BamHI-DraI DNA fragments on the plasmid
      and hc1 respectively. Comparison of these two DNA sequences using Bestfit program
      has identified a 24 bp region with >75% identity that is unique to the chlamydial
      genome. Double-stranded DNA prepared by annealing complementary oligonucleotides
      corresponding to the conserved 24 bp region bind Hc1, in contrast to control
      sequences with similar A+T ratios. Further, Hc1 binds to DNA in a strand specific
      fashion, with preferential binding for only one strand. The site specific
      affinity to plasmid DNA was also demonstrated by atomic force microscopy data
      images. Binding was always followed by coiling, shrinking and aggregation of the
      affected DNA. Very low protein-DNA ratio was required if incubations were carried
      out in solution. However, if DNA was partially immobilized on mica substrate
      individual strands with dark foci were still visible even after the addition of
      excess Hc1.

PMID- 8760884
TI  - Molecular cloning of a RNA binding protein, S1-1.
AB  - S1 proteins A-D constitute a nuclear protein family that are liberated rapidly in
      a set from chromatin by mild digestion with a DNA or RNA hydrolyzing enzyme. With
      an anti-S1-protein B antiserum that reacted with B2, C1 and D1, a cDNA clone, pS1
      1, was obtained, which encoded a protein of 852 amino acids. The S1-1 protein,
      encoded within the cells by a mRNA of 3480 nt, was a novel protein and could be
      distinguished from the S1 proteins B, C and D by their amino acid sequences. The
      S-1-1 protein synthesized by in vitro translation bound to RNA homopolymers, with
      a preference for G and U polyribonucleotides and little for poly(A). The protein
      contained two tandem RNP motifs and several intriguing sequences, such as a novel
      repeat of five octamers with a consensus sequence DP-S(Q/G)YYY and a potentially
      perfect amphipathic alpha-helix of five turns with basic and acidic amino acids
      positioned in an ordered way. The two RNP motif sequences were similar, although
      homologies were low, to the RNP motif sequences of yeast NSR1 protein, animal
      nucleolins, Drosophila hnRNP Al and tobacco chloroplast RNP precursor protein,
      suggesting a functional uniqueness of the S1-1 protein in RNA metabolism and also
      the evolution of its RNP motif structure before plants and animals diverged.
      These results indicate that the S1-1 protein encoded by the cDNA is a new class
      of RNA binding protein.

PMID- 8760885
TI  - DNA sequencing by hybridization to microchip octa-and decanucleotides extended by
      stacked pentanucleotides.
AB  - The efficiency of sequencing by hybridization to an oligonucleotide microchip
      grows with an increase in the number and in the length of the oligonucleotides;
      however, such increases raise enormously the complexity of the microchip and
      decrease the accuracy of hybridization. We have been developing the technique of
      contiguous stacking hybridization (CSH) to circumvent these shortcomings.
      Stacking interactions between adjacent bases of two oligonucleotides stabilize
      their contiguous duplex with DNA. The use of such stacking increases the
      effective length of microchip oligonucleotides, enhances sequencing accuracy and
      allows the sequencing of longer DNA. The effects of mismatches, base composition,
      length and other factors on the stacking are evaluated. Contiguous stacking
      hybridization of DNA with immobilized 8mers and one or two 5mers labeled with two
      different fluorescent dyes increases the effective length of sequencing
      oligonucleotides from 8 to 13 and 18 bases, respectively. The incorporation of
      all four bases or 5-nitroindole as a universal base into different positions of
      the 5mers permitted a decrease in the number of additional rounds of
      hybridization. Contiguous stacking hybridization appears to be a promising
      approach to significantly increasing the efficiency of sequencing by
      hybridization.

PMID- 8760886
TI  - Misincorporation rate and type on the leading and lagging strands of UV-damaged
      DNA.
AB  - We have examined the fidelity of replication of the leading and lagging strands
      of UV-irradiated DNA by using an EBV-derived shuttle vector system which contains
      as marker gene for mutation analysis the bacterial gpt gene in both orientations
      relative to the EBV oriP. Human cells stably transformed with this vector were UV
      irradiated and gpt mutation rate and type were analysed. An increased
      mutagenicity associated with UV irradiation was observed, but the average error
      frequency was unaffected by the direction of replication of the target gene. Some
      variability by position and sequence context of leading and lagging strand errors
      was detected, suggesting that the different architecture of the replication
      complex for the two strands might, to some extent, affect mutation spectra. The
      comparable fidelity of translesion replication on the leading and lagging strands
      is in agreement with the current model for eukaryotic replication that postulates
      the simultaneous synthesis of both strands by a DNA polymerase with a proof
      reading exonuclease.

PMID- 8760888
TI  - Identification and distribution of seven classes of middle-repetitive DNA in the
      Arabidopsis thaliana genome.
AB  - In order to analyse further the genomic distribution of repetitive sequences in
      the Arabidopsis genome, we have identified and characterized seven novel
      repetitive sequences. Analysis of genomic representation, genomic location and
      DNA sequence divided the seven repeated sequences into two classes. The first was
      represented by three cosmid subclones (182A, 74A, 191A) carrying sequences that
      hybridised to up to 20 genomic fragments and showed sequence homology to the
      genes, Arabidopsis CCR2, Arabidopsis MYB and to various ATP-binding transport
      proteins. These multigene families mapped to various positions within the genome,
      as judged by hybridization to YAC clones constituting the Arabidopsis physical
      map. The second class was represented by four cosmid subclones (106B, 164A, 163A,
      278A) that hybridised to between 20 and 300 genomic fragments. One of these,
      106B, is a diverged, partial copy of the LTR of the Arabidopsis retrotransposon
      Athila. The other three sequences showed no homology to known genes or proteins.
      The distribution of these sequences on chromosome 4 was analysed and sequences
      hybridizing to 106B, 164A and 163A were found exclusively at the centromeric
      region of this chromosome. Their detailed arrangement at the centromeric region
      of chromosome 4, relative to other repeated sequence families and single copy
      sequences, was determined.

PMID- 8760887
TI  - Selection of the best target site for ribozyme-mediated cleavage within a fusion
      gene for adenovirus E1A-associated 300 kDa protein (p300) and luciferase.
AB  - The cellular 300 kDa protein known as p300 is a target for the adenoviral E1A
      oncoprotein and it is thought to participate in prevention of the G0/G1
      transition during the cell cycle, in activation of certain enhancers and in the
      stimulation of differentiation pathways. In order to determine the exact function
      of p300, as a first step we constructed a simple assay system for the selection
      of a potential target site of a hammerhead ribozyme in vivo. For the detection of
      ribozyme-mediated cleavage, we used a fusion gene (p300-luc) that consisted of
      the sequence encoding the N-terminal region of p300 and the gene for luciferase,
      as the reporter gene. We were also interested in the correlation of the GUX rule,
      for the triplet adjacent to the cleavage site, with ribozyme activity in vivo.
      Therefore, we selected five target sites that all included GUX The rank order of
      activities in vitro indeed followed the GUX rule; with respect to the kcat, a C
      residue as the third base (X) was the best, next came an A residue and a U
      residue was the worst (GUC > GUA > GUU). However, in vivo the tRNA(Val) promoter
      driven ribozyme, targeted to a GUA located upstream of the initiation codon, had
      the highest inhibitory effect (96%) in HeLa S3 cells when the molar ratio of the
      DNA template for the target p300 RNA to that for the ribozyme was 1:4. Since the
      rank order of activities in vivo did not conform to the GUX rule, it is unlikely
      that the rate limiting step for cleavage of the p300-luc mRNA was the chemical
      step. This kind of ribozyme expression system should be extremely useful for
      elucidation of the function of p300 in vivo.

PMID- 8760889
TI  - Cloning and characterization of the major histone H2A genes completes the cloning
      and sequencing of known histone genes of Tetrahymena thermophila.
AB  - A truncated cDNA clone encoding Tetrahymena thermophila histone H2A2 was isolated
      using synthetic degenerate oligonucleotide probes derived from H2A protein
      sequences of Tetrahymena pyriformis. The cDNA clone was used as a homologous
      probe to isolate a truncated genomic clone encoding H2A1. The remaining regions
      of the genes for H2A1 (HTA1) and H2A2 (HTA2) were then isolated using inverse PCR
      on circularized genomic DNA fragments. These partial clones were assembled into
      intact HTA1 and HTA2 clones. Nucleotide sequences of the two genes were highly
      homologous within the coding region but not in the noncoding regions. Comparison
      of the deduced amino acid sequences with protein sequences of T. pyriformis H2As
      showed only two and three differences respectively, in a total of 137 amino acids
      for H2A1, and 132 amino acids for H2A2, indicating the two genes arose before the
      divergence of these two species. The HTA2 gene contains a TAA triplet within the
      coding region, encoding a glutamine residue. In contrast with the T. thermophila
      HHO and HTA3 genes, no introns were identified within the two genes. The 5'- and
      3'-ends of the histone H2A mRNAs; were determined by RNase protection and by PCR
      mapping using RACE and RLM-RACE methods. Both genes encode polyadenylated mRNAs
      and are highly expressed in vegetatively growing cells but only weakly expressed
      in starved cultures. With the inclusion of these two genes, T. thermophila is the
      first organism whose entire complement of known core and linker histones,
      including replication-dependent and basal variants, has been cloned and
      sequenced.

PMID- 8760890
TI  - Covalent attachment of synthetic DNA to self-assembled monolayer films.
AB  - The covalent attachment of thiol-modified DNA oligomers; to self-assembled
      monolayer silane films on fused silica and oxidized silicon substrates is
      described. A heterobifunctional crosslinking molecule bearing both thiol- and
      amino-reactive moieties was used to tether a DNA oligomer (modified at its
      terminus with a thiol group) to an aminosilane film formed on silica surfaces. A
      variety of aminosilanes, crosslinkers and treatment conditions have been tested
      to identify optimal conditions for DNA immobilization using this approach. The
      DNA films which result have been characterized using UV spectroscopy, water
      contact angle measurement, radiolabeling and hybridization methods.

PMID- 8760892
TI  - Acid binding and detritylation during oligonucleotide synthesis.
AB  - Under the conditions normally used for detritylation in oligonucleotide
      synthesis, the haloacetic acid binds strongly to the oligonucleotide.
      Acetonitrile also forms a complex with the deblocking acid, in competition with
      the oligonucleotide, and drastically slows detritylation. Incomplete removal of
      acetonitrile during the deblock step may slow the kinetics enough to result in
      incomplete detritylation of the oligonucleotide. Acid binding to the growing
      oligonucleotide causes striking chromatographic effects in the presence of high
      oligonucleotide mass densities. In packed-bed column reactors, at low linear
      velocities, the acid binding almost completely depletes free acid from the
      deblocking solution. This results in an advancing zone within which the
      oligonucleotide is saturated with acid. Detritylation occurs mostly in a narrow
      band at the front of the advancing saturated zone. Increasing the DCA
      concentration in order to achieve quick saturation can give faster and more
      complete detritylation while minimizing the exposure time of the oligonucleotide
      to acid.

PMID- 8760891
TI  - Fabrication of patterned DNA surfaces.
AB  - Two photolithographic methods are described for the formation of patterned single
      or multiple DNA species on SiO2 substrates. In the first approach, substrates are
      treated with a photochemically labile organosilane monolayer film. Irradiation of
      these surfaces with patterned deep UV (193 nm) light results in patterned
      chemically reactive groups which are then reacted with heterobifunctional
      crosslinking molecules. Covalent attachment of modified synthetic DNA oligomers
      to the crosslinker results in stable DNA patterns. Alternatively, a photoresist
      is spin-coated over a silane film which had been previously modified with the
      heterobifunctional crosslinker. Upon patterned irradiation and subsequent
      development, the underlying crosslinker-modified layer is revealed, and is then
      reacted with a chemically modified DNA. Feature dimensions to 1 micron are
      observed when a single fluorescent DNA is attached to the surface. By performing
      sequential exposures, we have successfully immobilized two distinguishable DNA
      oligomers on a single surface. Synthetic DNA immobilized in this manner retains
      the ability to hybridize to its complementary strand, suggesting that these
      approaches may find utility in the development of miniaturized DNA-based
      biosensors.

PMID- 8760893
TI  - Kinetic studies on depurination and detritylation of CPG-bound intermediates
      during oligonucleotide synthesis.
AB  - Fully protected CPG-immobilized monomer, dimer and trimer oligonucleotides were
      used to study depurination during the chemical synthesis of oligonucleotides.
      Disappearance of the oligonucleotide during acid exposure time relative to an
      internal thymidine standard not subject to depurination was monitored by reverse
      phase HPLC analysis. Depurination half-times obtained for dichloroacetic acid
      (DCA) and trichloroacetic acid (TCA) in methylene chloride were found to be 3%
      DCA >> 15% DCA > 3% TCA. In order to understand the implications of depurination
      during DNA synthesis, the detritylation kinetics of model compounds DMT-dG-pT
      dimer and DMT-[17mer] mixed-base sequence were also measured. These results
      improve our ability to properly balance the contradictory goals of obtaining
      maximum detritylation with minimum depurination in oligonucleotide synthesis.

PMID- 8760894
TI  - Stability of the human dystrophin transcript in muscle.
AB  - The human dystrophin gene has 79 exons spanning >2300 kb making it the largest
      known gene. In previous studies we showed that approximately 16 h are required to
      transcribe the gene in myogenic cultures [Tennyson, C.N., Klamut, H.J. and
      Worton, R.G. (1995) Nature Genet. 9, 184-190]. To estimate the half-life of the
      dystrophin mRNA, the decay of the transcript was monitored by quantitative RT-PCR
      in cultured human fetal myotubes following exposure to actinomycin D. Results
      from this analysis indicated that the half-life of the dystrophin mRNA is 15.6 +/
      2.8 h in these cultures. Transcript accumulation profiles were predicted using a
      mathematical model which incorporated the measured half-life. The modeled
      accumulation profiles were consistent with observed profiles supporting the half
      life measured using actinomycin D. The kinetic model was then used to predict the
      relative amount of nascent and mature dystrophin transcript at steady state.
      Measurements by quantitative RT-PCR indicated that in adult skeletal muscle
      tissue the concentration of mature dystrophin mRNA is 5-10 molecules per nucleus,
      demonstrating, as expected, that it is a low abundance transcript. Furthermore
      the ratio of nascent to mature dystrophin transcript indicated that dystrophin
      synthesis may not be at steady state in the adult skeletal muscle we tested.
      Alternatively, the kinetics of transcript production in skeletal muscle tissue
      may be different from those observed in cultured fetal myogenic cells.

PMID- 8760895
TI  - RNase E processing of essential cell division genes mRNA in Escherichia coli.
AB  - The ratio of the FtsZ to FtsA proteins determines the correct initiation of cell
      division in Escherichia coli. The genes for these proteins are contiguous on the
      chromosome. Although both genes are transcribed from common promoters, the
      presence of ftsZ-specific promoters, along with differences in the efficiency of
      translation of their respective mRNAs, contribute to the increased relative
      expression of ftsZ. We report here that the polycistronic ftsA-ftsZ transcripts
      are cleaved by RNase E and that this cleavage affects the decay of ftsA and ftsZ
      mRNA. As a consequence of the cleavage, RNase E also contributes to the
      differential expression of the two genes.

PMID- 8760896
TI  - Improving the fidelity of Thermus thermophilus DNA ligase.
AB  - The DNA ligase from Thermus thermophilus (Tth DNA ligase) seals single-strand
      breaks (nicks) in DNA duplex substrates. The specificity and thermostability of
      this enzyme are exploited in the ligase chain reaction (LCR) and ligase detection
      reaction (LDR) to distinguish single base mutations associated with genetic
      diseases. Herein, we describe a quantitative assay using fluorescently labeled
      substrates to study the fidelity of Tth DNA ligase. The enzyme exhibits
      significantly greater discrimination against all single base mismatches on the 3'
      side of the nick in comparison with those on the 5'-side of the nick. Among all
      12 possible single base pair mismatches on the 3'-side of the nick, only T-G and
      G-T mismatches generated a quantifiable level of ligation products after 23 h
      incubation. The high fidelity of Tth DNA ligase can be improved further by
      introducing a mismatched base or a universal nucleoside analog at the third
      position of the discriminating oligonucleotide. Finally, two mutant Tth DNA
      ligases, K294R and K294P, were found to have increased fidelity using this assay.

PMID- 8760898
TI  - Strand transfer is enhanced by mismatched nucleotides at the 3' primer terminus:
      a possible link between HIV reverse transcriptase fidelity and recombination.
AB  - Strand transfer catalyzed by HIV reverse transcriptase (RT) was examined. The
      system consisted of a 142 nt RNA (donor) to which a 50 nt DNA primer was
      hybridized. The primer bound such that its 3' terminal nucleotide hybridized to
      the 12th nt from the 5' end of the donor. The 3' terminal nucleotide on the
      primer was either a G, A or T residue. Since the corresponding nucleotide of the
      donor was a C, the G formed a matched terminus and the A or T a mismatched
      terminus. The efficiency with which DNA bound to the donor transferred to a
      second RNA, termed acceptor, was monitored. The acceptor was homologous to the
      donor for all but the last 9 nt at the 5' end of the donor. Therefore, homologous
      strand transfer could occur at any point prior to the DNA being extended into the
      nonhomologous region on the donor. Strand transfer occurred approximately twice
      as efficiently with the mismatched versus matched substrates. The mismatched
      nucleotide was fixed into transfer products indicating that excision of the
      mismatch was not required for RT extension or transfer. Results suggest that base
      misincorporations by RT may promote recombination by enhancing strand transfer.

PMID- 8760897
TI  - Identification of essential residues in Thermus thermophilus DNA ligase.
AB  - DNA ligases play a pivotal role in DNA replication, repair and recombination.
      Reactions catalyzed by DNA ligases consist of three steps: adenylation of the
      ligase in the presence of ATP or NAD+, transferring the adenylate moiety to the
      5'-phosphate of the nicked DNA substrate (deadenylation) and sealing the nick
      through the formation of a phosphodiester bond. Thermus thermophilus HB8 DNA
      ligase (Tth DNA ligase) differs from mesophilic ATP-dependent DNA ligases in
      three ways: (i) it is NAD+ dependent; (ii) its optimal temperature is 65 instead
      of 37 degrees C; (iii) it has higher fidelity than T4 DNA ligase. In order to
      understand the structural basis underlying the reaction mechanism of Tth DNA
      ligase, we performed site-directed mutagenesis studies on nine selected amino
      acid residues that are highly conserved in bacterial DNA ligases. Examination of
      these site-specific mutants revealed that: residue K118 plays an essential role
      in the adenylation step; residue D120 may facilitate the deadenylation step;
      residues G339 and C433 may be involved in formation of the phosphodiester bond.
      This evidence indicates that a previously identified KXDG motif for adenylation
      of eukaryotic DNA ligases [Tomkinson, A.E., Totty, N.F., Ginsburg, M. and
      Lindahl, T. (1991) Proc. Natl. Acad. Sci. USA, 88, 400-404] is also the
      adenylation site for NAD+-dependent bacterial DNA ligases. In a companion paper,
      we demonstrate that mutations at a different Lys residue, K294, may modulate the
      fidelity of Tth DNA ligase.

PMID- 8760899
TI  - Hyper-negative template DNA supercoiling during transcription of the tetracycline
      resistance gene in topA mutants is largely constrained in vivo.
AB  - The excess linking deficit of plasmid DNA from topoisomerase I-defective bacteria
      (topA mutants) results mainly from transcription and is commonly ascribed to
      unbalanced relaxation of transcription-induced twin-supercoiled domains. This
      defect is aggravated in genes for membrane-binding proteins (such as the tet
      gene) where anchoring of the transcription complex to the bacterial membrane is
      thought to enhance twin-domain partitioning. Thus, it is often assumed that the
      'hyper-negative' linking difference of plasmid DNA from topA mutants reflects
      unconstrained, hyper-negative DNA supercoiling inside the cell. We tested the
      validity of this assumption in the present study. A DNA sequence that undergoes a
      gradual B to Z transition under increasing negative superhelical tension was used
      as a sensor of unconstrained negative supercoiling. Z-DNA formation was probed at
      a site upstream from the inducible pTac promoter fused either to the tet gene or
      to the gene for cytosolic chloramphenicol acetyl transferase (cat). Although
      plasmid DNA linking deficit increased more extensively in topA mutants following
      tet activation than following cat activation, no significant differences were
      observed in the extents to which the B to Z DNA transition is stimulated in the
      two cases. We infer that the excess linking deficit of the tet-containing plasmid
      DNA reflects constrained negative DNA supercoiling inside the cell.

PMID- 8760900
TI  - Role of TATA box sequence and orientation in determining RNA polymerase II/III
      transcription specificity.
AB  - Work from a number of laboratories has indicated that the TATA box sequence can
      act as a basal promoter element not only for RNA polymerase II (RNAP II)
      transcription, but also for transcription by RNA polymerase III (RNAP III). We
      previously reported that, in the absence of other cis-acting elements, the
      canonical TATA sequence TATAAAAA specifically supported transcription by RNAP II
      in an unfractionated Drosophila nuclear extract, whereas the sequence TTTTTATA
      (the same sequence in reverse orientation) directed RNAP III transcription. We
      have now examined a variety of other TATA box sequences with regard to RNA
      polymerase selectivity and their ability to support RNAP III transcription. The
      results have allowed us to rank these TATA box sequences with respect to their
      relative strengths as RNAP III promoter elements in unfractionated Drosophila
      extracts. Further, the data indicate that T residues at positions 2 and 4 of the
      TATA box appear to be important determinants of RNAP III selectivity in this
      system, whereas A residues at these positions favor RNAP II transcription.
      Finally, the data suggest that transcription factors TFIID and TFIIIB, although
      both capable of binding a variety of TATA elements, have distinct sequence
      preferences for recognizing the TATA box and possibly the surrounding DNA.

PMID- 8760902
TI  - The use of histone as a facilitator to improve the efficiency of retroviral gene
      transfer.
AB  - Vectors based on murine C-type retroviruses are commonly used in biology. The
      efficiency of viral infection is normally increased by a facilitator, for example
      polybrene, DEAE-dextran or a liposome. The receptor for ecotropic viruses is a
      transporter for basic amino acids; we therefore explored the use of a highly
      basic protein, histone type IIA, as a facilitator. We show in several cell types
      that histone is as efficient as the other agents tested, and in some cases more
      so. This readily available reagent is thus likely to be useful in the wide range
      of studies that employ retroviral vectors.

PMID- 8760901
TI  - Phosphorylation of human replication protein A by the DNA-dependent protein
      kinase is involved in the modulation of DNA replication.
AB  - The single-stranded DNA-binding protein, Replication Protein A (RPA), is a
      heterotrimeric complex with subunits of 70, 32 and 14 kDa involved in DNA
      metabolism. RPA may be a target for cellular regulation; the 32 kDa subunit
      (RPA32) is phosphorylated by several cellular kinases including the DNA-dependent
      protein kinase (DNA-PK). We have purified a mutant hRPA complex lacking amino
      acids 1-33 of RPA32 (rhRPA x 32delta1-33). This mutant bound ssDNA and supported
      DNA replication; however, rhRPA x 32delta1-33 was not phosphorylated under
      replication conditions or directly by DNA-PK. Proteolytic mapping revealed that
      all the sites phosphorylated by DNA-PK are contained on residues 1-33 of RPA32.
      When wild-type RPA was treated with DNA-PK and the mixture added to SV40
      replication assays, DNA replication was supported. In contrast, when rhRPA x
      32delta1-33 was treated with DNA-PK, DNA replication was strongly inhibited.
      Because untreated rhRPA x 32delta1-33 is fully functional, this suggests that the
      N-terminus of RPA is needed to overcome inhibitory effects of DNA-PK on other
      components of the DNA replication system. Thus, phosphorylation of RPA may
      modulate DNA replication indirectly, through interactions with other proteins
      whose activity is modulated by phosphorylation.

PMID- 8760903
TI  - Cleavage of oligodeoxyribonucleotides from controlled-pore glass supports and
      their rapid deprotection by gaseous amines.
AB  - A novel method for the deprotection of oligodeoxyribonucleotides has been
      developed. Gaseous amines such as ammonia or methylamine were employed under
      pressure to achieve mild and rapid deprotection conditions. For example,
      oligodeoxyribonucleotides having a (tert-butyl)phenoxyacetyl group for the
      protection of the exocyclic amino function of cytosine, adenine and guanine were
      released from controlled-pore glass supports and fully deprotected by ammonia or
      methylamine under gas phase conditions, at room temperature, within 35 or 2 min
      respectively.

PMID- 8760904
TI  - A simple assay to determine the functionality of Cre or FLP recombination targets
      in genomic manipulation constructs.
AB  - We report the construction of two Escherichia coli strains (294-Cre and 294-FLP)
      which express either Cre- or FLP-recombinase. Plasmids containing authentic
      recognition targets for either recombinase (loxPs or FRTs) are recombined when
      propagated in the appropriate strain. 294-Cre and 294-FLP thus provide a simple
      test for the recombination competence of constructs that are designed for use in
      Cre- or FLP-mediated genomic manipulations.

PMID- 8760905
TI  - A hypothetical holoenzyme involved in the replication of the murein sacculus of
      Escherichia coli.

PMID- 8760906
TI  - Modified peptidoglycan chemical composition in shape-altered Escherichia coli.
AB  - Peptidoglycan synthesis and its fine chemical composition were studied in
      dividing cocci of Escherichia coli carrying the lov-1 mutation and in which the
      coccal shape was obtained either by mecillinam treatment or by transferring a
      pbpA mutation (penicillin-binding protein 2- phenotype), as compared to normal
      rods and non-dividing cocci. Synchronously dividing cocci showed peptidoglycan
      synthesis only in the cell cycle phase corresponding to cell septation. During
      the phase corresponding to lateral wall elongation, peptidoglycan synthesis was
      strongly reduced. This type of synthesis suggests that the dividing cocci
      consisted only of the two poles. Analysis of the muropeptide composition revealed
      a specific fourfold increase in the tetra-tetra-tetra trimer in dividing cocci as
      compared to non-dividing cocci or parental rods. We postulate that, in E. coli,
      the chemical composition of septal peptidoglycan differs from that of lateral
      wall peptidoglycan.

PMID- 8760907
TI  - Growth rate control of protein and nucleic acid content in Streptomyces
      coelicolor A3(2) and Escherichia coli B/r.
AB  - Escherichia coli possesses regulatory mechanisms that coordinate cell growth with
      the synthesis of essential macromolecules (protein, RNA and DNA). While
      fundamental differences have been identified in the growth habit and chromosome
      structure of E. coli and Streptomyces, little is known about these regulatory
      mechanisms in filamentous bacteria. This paper reports on the relationship
      between the macromolecule content of S. coelicolor A3(2) and its specific growth
      rate. The protein, RNA and DNA contents (g per 100 g biomass) of S. coelicolor
      A3(2) grown in steady-state continuous culture over a range of specific growth
      rates (0.025-0.3 h-1) were 31-45, 10-22 and 3.5-4.5% (w/w), respectively. This
      composition is qualitatively similar to that of other microorganisms. Changes in
      the macromolecular content of S. coelicolor A3(2) and E. coli B/r with specific
      growth rate appear to be essentially similar. However, the data indicate that the
      RNA content of S. coelicolor A3(2), grown under the conditions used, exceeds that
      of E. coli grown at the same specific growth rate. The data also suggest that
      overlapping rounds of replication are not a feature of DNA synthesis in S.
      coelicolor A3(2). This may be a function of the organism's low maximum specific
      growth rate. Alternatively, it may be a consequence of regulatory mechanisms
      which act to inhibit the initiation of DNA synthesis in a linear chromosome which
      is already undergoing replication.

PMID- 8760908
TI  - End-product control of enzymes of branched-chain amino acid biosynthesis in
      Streptomyces coelicolor.
AB  - In streptomycetes, the branched-chain amino acids leucine, isoleucine and valine
      may serve as precursors for commercially important polyketides, and it is of
      interest to investigate whether the availability of these amino acids affects the
      production of the secondary metabolites derived from them. This paper reports
      studies on end-product control in the model organism Streptomyces coelicolor of
      the enzymes acetohydroxy acid synthase (AHAS) and isopropylmalate synthase
      (IPMS), mediating steps in the pathways to isoleucine-valine and leucine
      respectively. Specific activities of both enzymes were similarly affected when
      minimal medium was supplemented with the amino acids singly or in combination.
      Isoleucine alone caused a 2- to 3-fold increase, while all three amino acids
      caused a 5- to 8-fold decrease. Growth of an ilv auxotroph in media with limiting
      isoleucine gave enzyme specific activities 4- to 6-fold higher than in
      unsupplemented minimal medium. Spontaneous mutants were obtained by growing S.
      coelicolor on minimal medium containing 4-azaleucine. At lease four patterns of
      end-product control were found among the mutants, one of which showed high
      constitutive levels of both enzymes (7- and 15-fold above unsupplemented minimal
      medium values for AHAS and IPMS respectively). It is concluded that the variation
      in specific activities of the two enzymes under different physiological and
      genetic conditions spans a range of around 50 to 100, and that S. coelicolor has
      molecular mechanisms capable of producing this response.

PMID- 8760909
TI  - Production of hybrid anthracycline antibiotics by heterologous expression of
      Streptomyces nogalater nogalamycin biosynthesis genes.
AB  - A cluster of anthracycline biosynthetic genes isolated from Streptomyces
      nogalater was expressed in Streptomyces lividans and in Streptomyces galilaeus. A
      12 kb DNA fragment cloned from this cluster in pIJ486 caused the production of a
      novel compound when introduced into S. lividans. The compound is derived from
      nogalonic acid methyl ester, an early intermediate in nogalamycin biosynthesis.
      Complementation with the cloned 12 kb fragment of S. galilaeus mutants blocked in
      aclacinomycin biosynthesis caused the production of hybrid anthracyclines.
      Cloning of the nogalamycin gene cluster should make possible a detailed study of
      the biosynthesis of this interesting antibiotic, as well as the production of
      novel anthracyclines of potential value as cytostatic drugs.

PMID- 8760910
TI  - Evidence for a novel class of microbial 3-deoxy-D-arabino-heptulosonate-7
      phosphate synthase in Streptomyces coelicolor A3(2), Streptomyces rimosus and
      Neurospora crassa.
AB  - The tryptophan-sensitive 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP)
      synthases from Streptomyces coelicolor A3(2), Streptomyces rimosus and Neurospora
      crassa have been purified to homogeneity. All three enzymes have a subunit Mr of
      54,000. The S. coelicolor DAHP synthase was physically and kinetically
      characterized and the N-terminal amino acid sequence was obtained. The N-terminal
      amino acid sequence could not be obtained for the enzymes from S. rimosus and N.
      crassa, their N-termini apparently being blocked. However, following proteolytic
      digestion, internal amino acid sequences were obtained from both enzymes. A
      comparison with the known DAHP synthase sequences indicated that these DAHP
      synthases are unrelated to other microbial DAHP synthase sequences but are
      similar to plant DAHP synthases. Up until now, two distinct classes of DAHP
      synthase have been described, one comprising exclusively enzymes from plants, the
      other restricted to enzymes from micro-organisms. These studies indicate that the
      class containing the plant DAHP synthases also contains enzymes from a microbial
      eukaryote and from several bacteria.

PMID- 8760911
TI  - The modE gene product mediates molybdenum-dependent expression of genes for the
      high-affinity molybdate transporter and modG in Azotobacter vinelandii.
AB  - The Azotobacter vinelandii mod locus, which is involved in high-affinity
      molybdate transport and the early event in Mo metabolism, consists of two
      divergently transcribed operons, modG and modEABC. modA, modB and modC encode the
      components of the high-affinity molybdate transporter, and modG encodes a Mo
      binding protein. High concentrations of Mo repressed transcription of both
      operons. The modEABC operon was also repressed by tungstate and to a lesser
      extent by vanadate. modE, the first gene in the modEABC operon, controlled the Mo
      dependent transcription of both operons. It was not involved in the metal
      regulation of alternative nitrogenase gene expression. Although a modE mutant
      constitutively expressed genes encoding the molybdate transporter, it had a
      reduced rate of Mo accumulation.

PMID- 8760912
TI  - Sequence analysis of the Bacillus subtilis chromosome region between the serA and
      kdg loci cloned in a yeast artificial chromosome.
AB  - The standard strategies of genome sequencing based on lambda-vector or cosmid
      libraries are only partially applicable to AT-rich Gram-positive bacteria because
      of the problem of instability of their chromosomal DNA in heterologous hosts like
      Escherichia coli. One complete collection of ordered clones known for such
      bacteria is that of Bacillus subtilis, established by using yeast artificial
      chromosomes (YACs). This paper reports the results of the direct use of one of
      the YAC clones from the above collection for the sequencing of the region cloned
      in it. The strategy applied consisted of the following: (i) construction of M13
      banks of the partially purified YAC DNA and sequencing of 800 M13 clones chosen
      at random; (ii) directed selection of M13 clones to sequence by using marginal
      contig fragments as hybridization probes; (iii) direct sequencing of joining PCR
      fragments obtained by combinations of primers corresponding to the ends of
      representative contigs. The complete 104,109 bp insert sequence of this YAC clone
      was thus established. The strategy used allowed us to avoid resequencing the two
      largest, previously sequenced, contigs (13,695 and 20,303 bp) of the YAC insert.
      We propose that the strategy used can be applied to the sequencing of the whole
      bacterial genome without intermediate cloning, as well as for larger inserts of
      eukaryotic origin cloned in YACs. Sequencing of the insert of the YAC clone 15-6B
      allowed us to establish the contiguous sequence of 127 kb from spollA to kdg. The
      organization of the newly determined region is presented. Of the 138 ORFs
      identified in the spollA-kdg region, 57 have no clear putative function from
      their homology to proteins in the databases.

PMID- 8760913
TI  - A Bacillus subtilis gene cluster similar to the Escherichia coli phosphate
      specific transport (pst) operon: evidence for a tandemly arranged pstB gene.
AB  - We have determined the complete nucleotide sequence of the Bacillus subtilis
      homologues of the Escherichia coli phosphate-specific transport (pst) genes in
      the framework of the international B. subtilis genome sequencing project. The pst
      genes in E. coli form an operon arranged in the order pstS, pstC, pstA, pstB and
      phoU. In the case of B. subtilis, there are also five ORFs presumably forming an
      operon. The deduced amino acid sequences of the products of these ORFs show
      striking similarities to their E. coli counterparts. Comparison of the
      organization of the pst operon of B. subtilis with that of E. coli revealed that
      the gene corresponding to phoU is missing, while there are two genes homologous
      to pstB in B. subtilis. The pst operon is located at 222 degrees on the B.
      subtilis chromosome.

PMID- 8760914
TI  - Bacillus subtilis mutS mutL operon: identification, nucleotide sequence and
      mutagenesis.
AB  - The Bacillus subtilis mutS and mutL genes, involved in the DNA mismatch repair
      system, have been cloned and characterized. From sequence analysis the two genes
      appear to be organized in a single operon, located immediately downstream of the
      cotE gene (approximately 150 degrees on the genetic map). The deduced MutS
      protein is 49% identical to HexA and MutL is 46% identical to HexB of
      Streptococcus pneumoniae. Deletion of both mutS and mutL resulted in an increase
      in the frequency of spontaneous mutations and abolished the marker effect
      observed in transformation. The expression of the mut operon was studied with the
      use of a mutSL-lacZ transcriptional fusion. An increase in expression was
      observed during late exponential growth.

PMID- 8760915
TI  - The phage-like element PBSX and part of the skin element, which are resident at
      different locations on the Bacillus subtilis chromosome, are highly homologous.
AB  - PBSX and skin are two unusual genetic elements resident on the Bacillus subtilis
      chromosome. PBSX is a phage-like element located at approximately 100 degrees
      which is induced by the SOS response and results in cell lysis with the release
      of phage-like particles. The phage particles contain bacterial chromosomal DNA
      and kill sensitive bacteria without injecting DNA. The skin element is located at
      approximately 230 degrees on the chromosome and is positioned within the sigK
      open reading frame (ORF). It is excised at a particular stage of sporulation,
      leading to reconstitution of the complete sigK gene. In this paper, we show that
      there are phage-like operons present in the skin element which are highly
      homologous to the region of PBSX comprising part of the control region and the
      late operon. These operons are similar in terms of their gene organization, the
      percentage identity of the products of homologous ORFs and the positioning and
      strengths of ribosome-binding sites for each ORF. Although this high degree of
      conservation suggests that the phange-like operons in skin can be expressed,
      expression of the late operon was not detected during exponential growth, during
      sporulation or after induction of the SOS response. However two non-phage-like
      operons in the skin element are expressed and have distinct expression profiles
      that are dependent on the growth and developmental status of the cell.

PMID- 8760916
TI  - A Bacillus subtilis secreted phosphodiesterase/alkaline phosphatase is the
      product of a Pho regulon gene, phoD.
AB  - A secreted phosphodiesterase/alkaline phosphatase, APaseD, was purified from a
      culture of Bacillus subtilis JH646MS. Its phosphodiesterase activity was
      reminiscent of an APase isolated and characterized previously. Immunoassay and N
      terminal sequencing showed the two proteins to be identical. Using the first 20
      amino acids of the mature protein, a BLAST search of GenBank was used to find an
      homologous sequence. An exact match was found but in a putative non-coding
      region. It was hypothesized that there was a base pair deletion in the phoD gene.
      A DNA fragment internal to the coding region was generated by PCR using template
      DNA from a strain which produced APaseD. The PCR fragment was cloned and used to
      interrupt the gene. Western blot analysis of the parent and the mutated strains
      showed that APaseD was missing in the mutant. Resequencing of the gene revealed a
      larger ORF encoding a protein similar in size to the 49 kDa APaseD estimated by
      SDS-PAGE. The promoter was then cloned, sequenced and used in phoD-lacZ promoter
      fusions which showed that the gene was phosphate-starvation-induced and dependent
      on PhoP and PhoR for expression.

PMID- 8760917
TI  - Genetic analysis of cryIIIA gene expression in Bacillus thuringiensis.
AB  - The Bacillus thuringiensis (Bt) cryIIIA gene is regulated by a different
      mechanism from that of most of the other cry genes. Its expression begins during
      late-exponential growth and not during sporulation as for the other classes of
      cry genes. Moreover, in Bacillus subtilis, cryIIIA expression is independent of
      the major sporulation-specific sigma factors and is increased in a spoOA genetic
      background. We used lacZ fusions and primer-extension analysis to follow the time
      course of cryIIIA transcription in Bt wild-type and in various Spo- genetic
      backgrounds (spoOA, sigE and sigK). cryIIIA was activated from the end of
      vegetative growth to stage II of sporulation (t3) in the wild-type strain.
      Thereafter, transcription from the same promoter continued, at a decreasing rate,
      until the end of stage III. In the spoOA mutant strain, the same promoter was
      activated for at least 15 h during the stationary phase. cryIIIA activation in
      the sigK genetic background was similar to that in the wild-type but was extended
      in a sigma E mutant strain. Thus cryIIIA expression in Bt is not directly
      dependent on the major sporulation-specific sigma factors. Furthermore, an event
      linked with the thE-dependent period of sporulation ends cryIIIA activation,
      although transcription of this gene does not switch off before the end of stage
      III.

PMID- 8760918
TI  - Translational control of puf operon expression in Rhodobacter sphaeroides 2.4.1.
AB  - The puf operon of Rhodobacter sphaeroides 2.4.1 encode the beta- and alpha
      polypeptides of the B875 complex, the L and M polypeptides of the reaction centre
      and the pufX gene product. A previous report from the authors' laboratory
      indicated the potential existence of a 20-codon open reading frame (orfK, now
      designated pufK) located immediately upstream of the pufB structural gene. It is
      now demonstrated that pufK is translated in vivo and that the specific levels or
      nature of the rare codons within pufK affect the expression of pufK. Using a
      series of pufK-specific mutations, both in trans as lacZ translational fusions
      and incorporated into the genome in single copy, evidence has been obtained that
      translation initiation through pufK may be essential to translation of pufB.
      Further, the abundance, quality and distribution of rare codons within pufK may
      serve to 'gate' the entry of ribosomes at pufB. The data also suggest that
      translation of pufB is uncoupled from that of pufA, with the latter capable of
      being produced in excess of the former. It is also revealed that the secondary
      structure at the 5' end of the large and small puf transcripts may play a role in
      mRNA stability and that stability of the small puf transcript is independent of
      translation.

PMID- 8760919
TI  - Cloning of the Rhodobacter sphaeroides hisL gene: unifunctionality of the encoded
      protein and lack of linkage to other his genes.
AB  - The Rhodobacter sphaeroides 2.4.1 hisI gene, which encodes a phosphoribosyl-AMP
      cyclohydrolase that catalyses the third step in the histidine biosynthetic
      pathway, has been isolated from a genomic library of this phototrophic bacterium
      by complementation of an Escherichia coli hisI mutant. Analysis of the nucleotide
      sequence of the R. sphaeroides hisI gene reveals that it encodes a deduced
      product of 119 aa with a predicted molecular mass of 13.4 kDa. In contrast to the
      situation in E. coli, the R. sphaeroides hisI gene encodes a unifunctional
      protein and it is not linked to the hisE gene. The absence of a single histidine
      operon like that of E. coli was confirmed by PFGE experiments and complementation
      analysis of a R. sphaeroides hisI mutant that was constructed by marker exchange.
      The location of hisI in the R. sphaeroides genome has been determined to be at
      map co-ordinate 2275 +/- 20 of chromosome l.

PMID- 8760920
TI  - Genetic manipulation of acid formation pathways by gene inactivation in
      Clostridium acetobutylicum ATCC 824.
AB  - Integrational plasmid technology has been used to disrupt metabolic pathways
      leading to acetate and butyrate formation in Clostridium acetobutylicum ATCC 824.
      Non-replicative plasmid constructs, containing either clostridial
      phosphotransacetylase (pta) or butyrate kinase (buk) gene fragments, were
      integrated into homologous regions on the chromosome. Integration was assumed to
      occur by a Campbell-like mechanism, inactivating either pta or buk. Inactivation
      of the pta gene reduced phosphotransacetylase and acetate kinase activity and
      significantly decreased acetate production. Inactivation of the buk gene reduced
      butyrate kinase activity, significantly decreased butyrate production and
      increased butanol production.

PMID- 8760921
TI  - Clostridium paradoxum DSM 7308T contains multiple 16S rRNA genes with
      heterogeneous intervening sequences.
AB  - Sequence analysis of the cloned 16S rRNA genes of Clostridium paradoxum DSM 7308T
      revealed the presence of 15 different sequences in variable region I (Escherichia
      coli position 73-97) of the 16S rRNA. The majority of the cloned genes contained
      intervening sequences (IVSs), which varied in length from 120-131 nt, and were
      present in the DNA obtained from single colonies of C. paradoxum. The absence of
      IVSs in the mature rRNA was demonstrated by Northern hybridization and sequence
      analysis of the 16S rRNA reverse transcriptase (RT)-PCR product. This finding was
      supported by the failure of oligonucleotide probes specific for certain IVSs to
      hybridize to the RT-PCR product obtained from C. paradoxum. Alterations in
      culture conditions (temperature, pH, salt) or culture age did not lead to
      expression of RNA containing IVSs, as indicated by the size of RT-PCR products.
      Hybridization of the restriction-enzyme-digested genomic DNA of C. paradoxum with
      probes derived from the IVSs demonstrated that the 16S rRNA genes containing
      different IVSs are located at different sites on the chromosome.

PMID- 8760922
TI  - Acyl carrier protein of Azospirillum brasilense: properties of the purified
      protein and sequencing of the corresponding gene, acpP.
AB  - Acyl carrier protein (ACP) plays a crucial role in bacterial fatty acid
      synthesis. Cloning genes encoding ACPs from Gram-negative bacteria in Escherichia
      coli is difficult due to adverse effects of the cloned gene on host cell
      viability, and we were unsuccessful in cloning the full length ACP gene (acpP)
      from Azospirillum brasilense using conventional methods. Therefore, ACP from A.
      brasilense was purified to homogeneity and a part of the acpP gene was cloned
      using the polymerase chain reaction (PCR) technique with two primers, one
      designed from the N-terminal amino acid sequence of the purified ACP and the
      other from the highly conserved amino acid sequence of bacterial ACPs. The
      nucleotide sequence of the gene was obtained by cloning and sequencing inverse
      PCR products containing the acpP region generated by two oppositely oriented
      internal primers designed from the partial acpP gene sequence using restriction
      enzyme-digested, self-circularized chromosomal DNA fragments as templates.
      Characterization of the purified ACP and analysis of the derived amino acid
      sequence of the acpP gene of A. brasilense revealed that: (a) the mature ACP,
      composed of 78 amino acids, is a highly expressed protein (about 2.0-3.0 x 10(4)
      molecules per cell), (b) compared to E. coli ACP, it has a more compact structure
      and contains significantly more hydrophobic amino acid residues and (c) the
      potential mRNA sequence of the ACP gene has some structural features typical of a
      stable mRNA.

PMID- 8760923
TI  - 16S-23S rDNA intergenic sequences indicate that Leuconostoc oenos is
      phylogenetically homogeneous.
AB  - The study of the intra-specific phylogenetic structure of Leuconostoc oenos is
      essential to understand the participation of several strains in malo-lactic
      fermentation (MLF). RFLP of the PCR-amplified 16S-23S rDNA intergenic spacer
      region (ISR) was performed in Leuc. oenos and other related species. The RFLP
      patterns with seven endonucleases were identical for the 37 Leuc. oenos strains,
      but differed from those obtained for all other species tested. This method could
      provide an invaluable insight for molecular identification of the wine
      leuconostocs. The RFLP relationships of members of the genera Leuconostoc and
      Weissella were highly similar to those previously reported by 16S and 23S rRNA
      sequencing studies. The 16S-23S rDNA ISR was sequenced in five strains of Leuc.
      oenos. A single tRNA(Ala) was detected. The ISR sequence seems to be identical in
      the two rRNA (rrn) operons found in Leuc. oenos and no significant sequence
      variation was observed between strains that revealed relative differences as
      previously shown by PFGE. Results from the present study demonstrated that Leuc.
      oenos is phylogenetically a very homogeneous species (according to DNA-DNA
      hybridization studies) and sustain that this species is different from the genus
      Leuconostoc. The extremely conserved ISR of these organisms suggests that Leus.
      oenos strains currently isolated and characterized must have spread with the
      transfer of viticulture rather than coming from indigenous populations.

PMID- 8760924
TI  - In vitro formation of a catabolic plasmid carrying Klebsiella pneumoniae DNA that
      allows growth of Escherichia coli K-12 on 3-hydroxybenzoate.
AB  - The four enzymes needed to convert 3-hydroxybenzoate to pyruvate and fumarate via
      the gentisate pathway, as well as a putative positive regulator protein, were
      encoded on an 8 kb Sphl fragment of Klebsiella pneumoniae DNA. The five genes
      were clustered in the order regulator-gentisate dioxygenase-fumarylpyruvate
      hydrolase-3-hydroxybenzoate monooxygenase-maleylpyruvate isomerase (mhbRDHMI),
      with the catabolic genes transcribed in the dioxygenase to isomerase direction. 2
      Hydroxybenzoate was found to be a non-metabolizable inducer analogue for the mhb
      genes, supporting the view that gentisate rather than maleylpyruvate was the
      physiological inducer. The plasmid pNDR20 encoding the full gentisate catabolic
      pathway endowed Escherichia coli with the ability to grow on 3-hydroxybenzoate
      but the host cell appeared to be responsible for substrate uptake.

PMID- 8760925
TI  - SomA, a novel gene that encodes a major outer-membrane protein of Synechococcus
      sp. PCC 7942.
AB  - The outer membrane of a cyanobacterium (Synechococcus sp. strain PCC 7942)
      contains only a few major proteins. A gene encoding one of them, somA, was cloned
      and characterized. Based on the nucleotide sequence, SomA was predicted to
      comprise 531 amino acids with a calculated molecular mass of 57,136 Da. The
      deduced amino acid sequence of SomA shares similarities with two bacterial cell
      surface proteins, the S-layer protein of Thermus thermophilus and the flagellin
      of Campylobacter coli. The predicted amino acid sequence of SomA revealed also
      that it contains a signal peptide-like sequence at its N terminus. This signal
      peptide-like sequence was capable of mediating protein translocation across the
      cytoplasmic membrane into the outer membrane of Escherichia coli, provided that
      this sequence was fused to the E. coli outer-membrane protein, OmpF. The signal
      peptide-like sequence was cleaved upon the translocation of the SomA::OmpF
      protein. We suggest that SomA is synthesized as a precursor and that its N
      terminal 24 amino acid sequence is a cleavable signal peptide involved in protein
      targeting into the outer membrane. To our knowledge, this is the first example of
      cleavable signal peptides for proteins transported into the outer membrane of
      cyanobacteria.

PMID- 8760926
TI  - The non-haem chloroperoxidase from Pseudomonas fluorescens and its relationship
      to pyrrolnitrin biosynthesis.
AB  - The non-haem chloroperoxidase gene (cpoF) from the pyrrolnitrin producer
      Pseudomonas fluorescens BL914 was cloned using an oligonucleotide derived from
      part of the N-terminal amino acid sequence of chloroperoxidase (CPO-P) from
      Pseudomonas pyrrocina as a probe. Based on the overexpression of cpoF in
      Escherichia coli and the stability of CPO-F against higher temperatures and
      proteases, the enzyme was purified to homogeneity. Partial characterization of
      the enzyme showed that it belongs to the class of bacterial non-haem CPOs. To
      investigate the role of CPO-F in pyrrolnitrin biosynthesis, the cpoF gene was
      inactivated by insertion of a kanamycin cassette. Exchange of the chromosomal
      cpoF gene against the disrupted copy had no influence on pyrrolnitrin production
      demonstrating that CPO-F was not involved in pyrrolnitrin biosynthesis.

PMID- 8760927
TI  - Protein C (OprC) of the outer membrane of Pseudomonas aeruginosa is a copper
      regulated channel protein.
AB  - Protein C (OprC) of the outer membrane of Pseudomonas aeruginosa forms small
      channels, as assayed by the liposome swelling method. We report here that OprC
      functions as a channel-forming and copper-binding protein. OprC purified to
      homogeneity formed a channel in planar lipid bilayers with an ion conductance of
      about 200 pS in 1 M NaCl. Cloning and sequencing of the gene encoding OprC
      revealed that it specified a polypeptide comprising 723 and 668 amino acid
      residues for the precursor and mature polypeptides (M(r) 73,372), respectively.
      The amino acid sequence of OprC showed the highest degree of similarity with that
      of NosA of Pseudomonas stutzeri (65% sequence identity) which conveys Cu2+ to
      intracellular acceptor(s). OprC showed high copper-binding activity (Kd = 2.6
      microM) in aqueous solution containing surfactant. The expression of OprC
      appeared to be repressed by exogenous Cu2+ and derepressed by anaerobiosis in the
      presence of nitrate. These results suggest that OprC might be involved in copper
      utilization.

PMID- 8760928
TI  - Flagellin gene and protein variation amongst clinical isolates of Pseudomonas
      aeruginosa.
AB  - Flagellin gene sequences from 64 clinical isolates of the opportunistic pathogen
      Pseudomonas aeruginosa were amplified by PCR and subjected to RFLP analysis by
      using seven restriction enzymes to digest the amplified products. Using this
      approach the isolates were assigned to one of 13 groups. The method was rapid,
      reproducible and applicable to all isolates. In contrast, serotyping failed to
      satisfactorily resolve 49% of the strains tested. The vast majority of clinical
      isolates generated amplified products of 1.02 kb (type a) or 1.25 kb (type b).
      Electron microscopical analysis revealed evidence fax some. flagellar structural
      variation between P. aeruginosa strains. This study provides further evidence
      that the flagellin gene is a widely applicable and useful genetic marker for
      studying genetic variation within populations of closely related bacteria.

PMID- 8760929
TI  - A low-fibronectin-binding mutant of Staphylococcus aureus 879R4S has Tn918
      inserted into its single fnb gene.
AB  - A low-fibronectin-binding mutant of Staphylococcus aureus strain 879R4SSp
      generated by transposon Tn918 mutagenesis is attenuated in a rat endocarditis
      model (J.M. Kuypers & R.A. Procter, 1989, Infect Immun 57, 2306-2312). PCR and
      Southern hybridization analysis with primers and probes, respectively, for the
      fnbA and fnbB genes of strains 8325-4 showed that strain 879R4SSp possesses a
      single fnb gene which is homologous to fnbA. This was confirmed by sequencing 41
      bp of 5' non-coding and 237 bp of 5' coding DNA, which showed 97% base identity
      to fnbA. Southern hybridization and sequencing showed that Tn918 was inserted 41
      bp 5' to fnbA in the mutant 879R4SSp/1536, between the promoter and initiation
      codon. Reduced adherence of the mutant to surface-bound fibronectin correlated
      with lower expression of a 180 kDa wall-associated fibronectin-binding protein.

PMID- 8760930
TI  - Capnocytophaga gingivalis: effects of glucose concentration on growth and
      hydrolytic enzyme production.
AB  - In chemostat culture, the microaerophilic, CO2 requiring, gingival-plaque
      associated bacterium Capnocytophaga gingivalis responded to the addition of
      glucose (1-6 g I-1) by doubling its growth rate and increasing its biomass yield
      fivefold. The data suggest that the glucose is catabolized by a fully aerobic
      route. Rather than repressing hydrolytic enzymes which might be associated with
      pathogenic properties, glucose enhanced the specific activity of aminopeptidase,
      trypsin-like protease, acid and alkaline phosphatase and alpha-glucosidase in
      comparison with a control culture grown in a tryptone/thiamin medium. Thus, the
      supply of glucose could be of importance in maximizing the pathogenic potential
      of this organism.

PMID- 8760931
TI  - A putative integrase gene defines the distal end of a large cluster of ToxR
      regulated colonization genes in Vibrio cholerae.
AB  - A large cluster of virulence genes encoding proteins involved in Vibrio cholerae
      accessory colonization factor (ACF) expression and toxin-coregulated pilus (TCP)
      biogenesis is flanked by sequences that resemble bacteriophage attachment (att)
      half-sites. Adjacent to the attL-like site is a gene (int) that encodes a protein
      related to the integrase family of site-specific recombinases. The putative
      vibrio integrase appears to be most closely related to the Escherichia coli
      cryptic prophage (CP4-57) integrase protein (52% identity, 73% similarity).
      Genomic analysis of numerous V. cholerae strains (O1, non-O1 and O139) revealed
      that only vibrios capable of causing epidemic Asiatic cholera possess the TCP-ACF
      colonization gene cluster in association with the integrase. The fact that the
      integrase gene is absent in avirulent strains suggests that epidemic strains of
      V. cholerae obtained the TCP-ACF colonization gene cluster via horizontal
      transfer.

PMID- 8760932
TI  - Rapid invasion by colicinogenic Escherichia coli with novel immunity functions.
AB  - Bacteriocins have been suggested to play an important role in the invasion
      dynamics of bacteria. Recently, the 'diversifying selection' hypothesis has been
      proposed, which addresses the origin and diversification of one group of
      bacteriocins, the colicins of Escherichia coli. According to this hypothesis,
      novel colicin gene clusters arise from mutations generating expanded immunity
      functions. Positive selection, favouring these novel immunities, then rapidly
      drives strains carrying the evolved colicin gene clusters to fixation in the
      local population. To test this fixation step driven by selection, invasion
      experiments were carried out by introducing novel colicinogenic strains into
      established colicinogenic populations. In all cases, invasion by strains
      expressing novel immunity functions occurred rapidly, even when initial
      frequencies of the invader were quite low. These invasions were attributed
      primarily to colicin killing effect. Other factors, such as growth rate, level of
      colicin production and stationary-phase survival rate, were shown to play very
      minor roles in the invasion process. These results provide direct evidence for
      the hypothesis of diversifying selection acting on colicin gene clusters and shed
      light on the ecological role of colicins.

PMID- 8760934
TI  - Endophytic taxol-producing fungi from bald cypress, Taxodium distichum.
AB  - Pestalotiopsis microspora occurs as a range of strains in bald cypress, Taxodium
      distichum. The organisms live as endophytes in the bark, phloem and xylem, and
      isolates show differences in cultural and microscopic characteristics on common
      laboratory media. Many of these fungi make taxol as determined by the reactivity
      of partially purified culture extracts with specific monoclonal antibodies
      against taxol. In the case of one strain of P. microspora (CP-4), taxol was
      isolated from culture medium and was shown to be identical to authentic taxol by
      chromatographic and spectroscopic means.

PMID- 8760933
TI  - Attachment of Vibrio alginolyticus to chitin mediated by chitin-binding proteins.
AB  - Vibrio alginolyticus is the only culturable vibrio associated with the
      chitinaceous carapace of the copepod Tigriopus fulvus (Fisher 1860) living in
      Ligurian coastal rock pools (Tyrrhenian Sea). The characteristics of the
      interaction between chitin particles and V. alginolyticus were studied by
      analysing strains isolated both from the copepod surface and from rock-pool
      water. The highest degree of attachment to chitin was observed at 20 degrees C,
      in the presence of 3% NaCl. Bacterial treatment with N-acetylglucosamine and
      pronase E caused a reduction in attachment of 52-62% and 77-94%, respectively.
      Chitin pretreatment with either wheat germ agglutinin or membrane proteins (MPs)
      from V. alginolyticus caused a reduction in attachment, of 50-57% and 53-70%,
      respectively. No inhibition was observed when bacteria were pretreated with D
      glucose, D-fucose or D-fructose, or when chitin was pretreated with concanavalin
      A and Escherichia coli DH5 alpha MPs. V. alginolyticus MPs able to bind chitin
      were isolated and analysed by SDS-PAGE. Four chitin-binding proteins were
      visualized in all tested strains (53, 35, 20 and 14 kDa); in vivo these peptides
      may efficiently mediate V. alginolyticus attachment to chitin-containing
      substrates.

PMID- 8760935
TI  - SP75 is encoded by the DP87 gene and belongs to a family of modular Dictyostelium
      discoideum outer layer spore coat proteins.
AB  - Highly purified spore coats of Dictyostelium discoideum each contained about 5 x
      10(6) protein molecules as determined by amino acid composition analysis. By two
      dimensional gel electrophoresis the coats were found to contain nine major
      abundance and numerous minor protein species, most of which were highly enriched
      relative to the adjacent interspore matrix. Protein was nearly quantitatively
      eluted by denaturants and 2-mercaptoethanol, showing that it was not irreversibly
      cross-linked. Because a reducing agent is required together with denaturants to
      elute most proteins if their free thiol groups have been prealkylated, it was
      concluded that the D. discoideum spore coat proteins are disulfide cross-linked
      into the matrix. One major coat protein, SP75, was partially sequenced and found
      to be encoded by the previously identified DP87 gene; this finding was supported
      by additional physical, genetic, biochemical and microscopic evidence. The five
      major proteins for which genes have been cloned were associated with the outer
      layer of the coat. In coats missing one or more of four of these proteins as a
      result of gene disruption, there were physical changes but, with one exception,
      the other major coat proteins appeared to be incorporated normally. Sequence
      analysis showed that these five outer layer coat proteins are homologous and
      consist of alternating sequence motifs related to epithelial mucin repeats, basic
      proline repeats found in salivary acidic proline-rich proteins, the NH2-terminal
      subdomain of epidermal growth factor modules and other cysteine repeats. Based on
      these and other observations, outer layer coat proteins are predicted to organize
      indeterminately to form a cell surface microenvironment supportive of cellulose
      morphogenesis during spore coat formation.

PMID- 8760936
TI  - Cytoplasmic localization of the white phase-specific WH11 gene product of Candida
      albicans.
AB  - Cells of Candida albicans WO-1 switch frequently, spontaneously and reversibly
      between a white and opaque phase. The white-opaque transition involves the
      regulation of phase-specific genes. In the white budding phase, cells express the
      white phase-specific gene WH11, which encodes a protein with homology to the heat
      shock protein Hsp12 of Saccharomyces cerevisiae. A recombinant Wh11 protein has
      been synthesized, purified to apparent homogeneity and used to generate a rabbit
      polyclonal antiserum. The antiserum was used to localize the Wh11 protein in
      white phase cells. Wh11 is distributed throughout the cytoplasm but appears to be
      excluded from vesicles, plasma membrane and nucleus. An analysis by Western
      blotting of Wh11 expression in a number of C. albicans strains and related
      species suggests a correlation between round budding cell shape and expression.

PMID- 8760937
TI  - A comparative study of the incorporation of a 1,6-beta-glucan and an O
      glycosylated protein epitope into the cell wall of Candida albicans.
AB  - The topological distribution of two epitopes in the cell wall of Candida
      albicans, the kinetics of their incorporation into the regenerating protoplast
      wall, and the effect of different antibiotics upon their incorporation and
      localization have been studied. To do so, two monoclonal antibodies that react
      against an O-glycosylated mannoprotein (1B12) and against a 1,6-beta-glucan
      epitope (JRR1) were used. The results show that the JRR1 epitope is localized in
      an internal layer of the cell wall, in contrast to the 1B12 epitope, which is
      superficial, and that the incorporation of the JRR1 epitope into walls of
      regenerating protoplasts precedes that of the 1B12 epitope. The JRR1 epitope is
      normally found in the culture medium of control cells, but not in that of
      papulacandin-B-treated cells, and tunicamycin interferes with the incorporation
      of the 1B12 epitope into the cell walls. Finally, the results support the
      hypothesis that mannoproteins are not 1,6-beta-glycosylated before their
      secretion.

PMID- 8760938
TI  - Evidence for different mannosylation processes involved in the association of
      beta-1,2-linked oligomannosidic epitopes in Candida albicans mannan and
      phospholipomannan.
AB  - A monoclonal antibody specific for beta-1,2-linked oligomannosides was used to
      study the association of these residues with Candida albicans mannan and
      phospholipomannan (PLM) in relation to growth conditions and in mannan mutant
      strains. Double immunofluorescence assays performed on cells grown under standard
      conditions indicated a highly heterogeneous cell surface expression of these
      epitopes in comparison with the homogeneous expression of alpha-linked
      oligomannosidic epitopes. Growth in the presence of tunicamycin, which inhibits
      mannan N-glycosylation, resulted in an absence of beta-1,2-oligomannosidic
      epitopes on the cell surface, although PLM synthesis still occurred as shown by
      autoradiography. Similarly, growth in acidic conditions, which inhibits the
      incorporation of beta-1,2-oligomannosides in mannan, resulted in an absence of
      beta-1,2-oligomannosidic epitopes at the cell surface, although they still
      associated with PLM as shown by Western blotting. Western blots of C. albicans
      mutant strains with reduced amounts or an absence of phosphorus and acid-labile
      beta-1,2-oligomannosides in their mannan confirmed that the association of beta
      1,2-linked oligomannosides with mannan and with PLM involves different
      mannosylation processes.

PMID- 8760939
TI  - Effect of monoclonal antibodies directed against Candida albicans cell wall
      antigens on the adhesion of the fungus to polystyrene.
AB  - The adhesion of Candida albicans to polystyrene and the effect of three
      monoclonal antibodies (mAbs) reactive with C. albicans cell wall surface antigens
      on this process was assessed in vitro with several C. albicans strains. In the
      absence of mAbs, adhesion of C. albicans to polystyrene increased in parallel
      with germ-tube formation. However, the growth of the strains in the yeast phase
      at 25 degrees C or the use of an agerminative mutant inhibited adhesion to
      polystyrene. Serotype A and B strains showed similar kinetics of adhesion to
      polystyrene and no statistically significant differences in germination or
      adhesion were observed when strains from the two serotypes were compared. The
      three mAbs had different effects on both germination and adhesion of C. albicans.
      mAbs 3D9 showed no influence on either germination or adhesion to polystyrene in
      two C. albicans strains. mAb B9E decreased both adhesion (45.6%) and
      filamentation (52.6%), and mAb 21E6 decreased filamentation (34.0%) but enhanced
      adhesion by 23.3%. This enhancement was also observed with the agerminative
      mutant and it was dose-dependent. It was not related to the binding capacity of
      the MAb to polystyrene nor to an increase in cell surface hydrophobicity of the
      antibody-treated cells. In conclusion, both growth phases of C. albicans can
      adhere to polystyrene, although the conditions for this process seem to be
      different in each phase. The two types of adhesion of C. albicans to polystyrene
      might have a role in the colonization of medical implants. The disparate effects
      shown by mAbs directed against cell wall mannoproteins of C. albicans on the
      adhesion of the fungus to polystyrene should be taken into consideration when
      designing strategies to block the adhesion of C. albicans to plastic materials
      with mAbs.

PMID- 8760940
TI  - Ribosomal protein gene transcription in Saccharomyces cerevisiae shows a biphasic
      response to nutritional changes.
AB  - Nutrients are major determinants of ribosomal protein (rp-) gene transcription in
      Saccharomyces cerevisiae. In order to investigate the molecular mechanisms
      underlying this nutritional control, yeast mutants that display defects in the
      glucose up-shift response of rp-gene transcription were isolated. Interestingly,
      although growth of these mutants on glucose-containing medium was severely
      affected an initial increase in rp-gene transcription by nutritional up-shift was
      still observed. However, at later time points, rp-mRNA levels decreased strongly.
      Various other types of severe growth limitation also did not prevent the initial
      up-shift in transcription. The results suggest that the glucose up-shift response
      of rp-gene transcription comprises two phases: an initial, transient response
      independent of the actual growth potential, and a sustained response which is
      dependent on growth and requires both glucose and adequate nitrogen sources.
      Previously, it was found that protein kinase A (Pka) mediates the initial up
      shift response, without the need for regulation of Pka activity by cAMP. The
      present data substantiate that, besides the RAS/adenylate cyclase pathway, an
      alternative pathway through Pka regulates rp-gene transcription. In addition,
      evidence is presented that the sustained response does not require Pka activity.
      Based on these results, taken together, a model is proposed in which rp-gene
      transcription is dynamically regulated by multiple signal transduction pathways.

PMID- 8760941
TI  - LAG2, a gene that determines yeast longevity.
AB  - Saccharomyces cerevisiae has a limited life span, measured by the reproductive
      capacity of the individual cell. Several genes that are differentially expressed
      during the yeast life span have been isolated. One of these genes, LAG2, has been
      characterized for its role in longevity. LAG2 is preferentially expressed in
      young cells. It encodes a predicted 680 amino acid protein with a putative
      transmembrane helix. The sequences does not show significant similarity to any
      other DNA or protein sequences in the databases. Deletion of LAG2 in a haploid
      strain did not affect growth, but it resulted in a 50% decrease in the mean and
      maximum life span. When LAG2 was overexpressed, the mean and maximum life span of
      the yeasts was extended by about 36% and 54%, respectively. These results
      indicate that this is a longevity-assurance gene in yeast.

PMID- 8760942
TI  - Physiological effects of nitrogen starvation in an anaerobic batch culture of
      Saccharomyces cerevisiae.
AB  - The effects of nitrogen starvation on the anaerobic physiology of Saccharomyces
      cerevisiae were studied in cells cultivated in a bioreactor. The composition of
      the mineral medium was designed such that the nitrogen source became depleted
      while there was still ample glucose left in the medium. The culture was
      characterized by acoustic gas analysis, flow injection analysis and HPLC analysis
      of extracellular substrates and metabolites. During the cultivation, the
      macromolecular composition of the cells was analysed with respect to the cellular
      content of RNA, protein, trehalose and glycogen. During exponential growth under
      anaerobic conditions, the maximum specific growth rate conditions. Depletion of
      ammonium in the medium led to an abrupt decrease (mumax) of S. cerevisiae CBS
      8066 (0.46 h-1) was identical to the mumax determined under aerobic in the flux
      through glycolysis. Subsequently, a continuous decrease in the carbon dioxide
      evolution rate, caused by catabolite inactivation of the hexose-transport system,
      was observed. The apparent half-life of the transport system under nitrogen
      starvation was 13 h. During the exponential growth phase, the cellular content of
      RNA and protein was 15% (w/w) and 60% (w/w), respectively. At the end of the
      cultivation where the cells had been starved of nitrogen for 18 h, the cellular
      content of RNA and protein had decreased to 4% (w/w) and 22% (w/w), respectively.
      The intracellular carbohydrate content increased dramatically as trehalose and
      glycogen accumulated to final concentrations of 7% (w/w) and 25% (w/w),
      respectively. Glycerol formation during nitrogen starvation was higher than that
      accounted for by the formation of organic acids, suggesting a protein turnover of
      approximately 6% h-1. The growth energetics of S. cerevisiae CBS 8066 also
      changed as a result of nitrogen starvation, and YxATP was observed to increase
      from 80 mmol g-1 during the exponential growth phase to more than 130 mmol g-1
      towards the end of the cultivation. The presented results illustrate the effect
      of nitrogen starvation on glycerol formation, protein turnover, catabolite
      inactivation of the sugar-transport system, the cellular composition, the cell
      cycle and growth energetics.

PMID- 8760943
TI  - The plasmin-binding protein Plr of group A streptococci is identified as
      glyceraldehyde-3-phosphate dehydrogenase.
AB  - Group A streptococci bind the serine protease plasmin with high affinity.
      Previously, a 41 kDa protein was identified as a candidate plasmin receptor
      protein (Plr) from group A streptococcal strain 64/14. The plr gene encoding Plr
      was cloned and the deduced amino acid sequence of Plr had significant similarity
      to glyceraldehyde-3-phosphate dehydrogenases (GAPDHs). In this study we have
      isolated cytoplasmic GAPDH of streptococcal strain 64/14. This enzyme was
      examined, on both structural and functional levels, for its relatedness to the
      Plr of strain 64/14 purified from mutanolysin extract and to recombinant Plr. We
      report here that no differences were detected between streptococcal Plr and
      cytoplasmic GAPDH on the basis of antibody reactivity, plasmin-binding activity,
      GAPDH activity, N-terminal amino acid sequence, peptide map analysis by V8
      protease digestion and amino acid composition analysis. Furthermore, the plr gene
      appears to be present as a single copy in group A streptococci.

PMID- 8760944
TI  - Vero cytotoxin-producing Escherichia coli, particularly serogroup O157,
      associated with human infections in England and Wales: 1992-4.
AB  - Investigations were performed by the Laboratory of Enteric Pathogens on Vero
      cytotoxin-producing Escherichia coli (VTEC) in England and Wales from 1992-4.
      Bacterial isolates, faeces and sera obtained from patients with diarrhoea, bloody
      diarrhoea and haemolytic uraemic syndrome were examined. Using serotyping, Vero
      cytotoxin gene probing and serodiagnostic tests for E. coli O157, evidence of
      infection was detected in 543, 434 and 491 individuals in 1992, 1993 and 1994
      respectively; VTEC of serogroup O157 were isolated from 470, 385 and 411 cases.
      The O157 VTEC strains belonged to at least 19 different phage types (PT) although
      84% belonged to PT2, PT49, PT8, PT1 or PT4. Antibodies to E. coli O157
      lipopolysaccharide were detected in 13% of the cases. The average annual rate of
      infection with O157 VTEC was 0.83/100000 and 12% of the 1458 individuals with
      evidence of infection with VTEC or E. coli O157 developed haemolytic uraemic
      syndrome. There were at least 18 general outbreaks and many family outbreaks.

PMID- 8760945
TI  - Enteroaggregative Escherichia coli associated with an outbreak of diarrhoea in a
      neonatal nursery ward.
AB  - Over a 9-day period in February 1995, 16 newborn babies (age range 2-11 days) and
      3 infants (24, 47 and 180 days of age) in a neonatal nursery ward developed
      diarrhoea accompanied by pyrexia and weight loss. Known enteropathogens were not
      detected in their stools but Escherichia coli displaying aggregative adherence to
      HEp-2 cells (enteroaggregative E. coli) were found in 12 (63%) ill infants and in
      none of 5 well neonates (P = 0.02). The illness lasted 3-9 days (mean 5.2) in 16
      babies, whereas in 3 neonates it showed a protracted course of 18-20 days. The
      source of infection and the mode of transmission remained unclear. The outbreak
      isolates manifested properties common in this new group of diarrhoeagenic E.
      coli: mannose-resistant haemagglutination, haemolysis on blood agar, and clump
      formation in liquid culture medium. They belonged to the O4 E. coli serogroup and
      expressed multiple antibiotic resistance.

PMID- 8760947
TI  - Recurrent outbreaks of Salmonella Enteritidis infections in a Texas restaurant:
      phage type 4 arrives in the United States.
AB  - In recent years infection caused by Salmonella serotype Enteritidis (SE) phage
      type 4 has spread through Europe but has been uncommon in the USA. The first
      recognized outbreak of this strain in the USA occurred in a Chinese restaurant in
      EI Paso, Texas, in April 1993; no source was identified. In September 1993, a
      second outbreak caused by SE phage type 4 was associated with the same
      restaurant. To determine the cause of the second outbreak, we compared food
      exposures of the 19 patients with that of two control groups. Egg rolls were the
      only item significantly associated with illness in both analyses (first control
      group: odds ratio [OR] 8.2, 95% confidence interval [CI] 2.3-31.6; second control
      group: OR 13.1, 95% CI 2.1-97.0). Retrospective analysis of the April outbreak
      also implicated egg rolls (OR 32.4, 95% CI 9.1-126.6). Egg roll batter was made
      from pooled shell eggs and was left at room temperature throughout the day. These
      two outbreaks of SE phage type 4 likely could have been prevented by using
      pasteurized eggs and safe food preparation practices.

PMID- 8760946
TI  - Distribution, gene sequence and expression in vivo of the plasmid encoded
      fimbrial antigen of Salmonella serotype Enteritidis.
AB  - The pefA gene which encoded the serotype associated plasmid (SAP) mediated
      fimbrial major subunit antigen of Salmonella enterica serotype Typhimurium shared
      genetic identity with 128 of 706 salmonella isolates as demonstrated by dot
      (colony) hybridization. Seventy-seven of 113 isolates of Typhimurium and
      individual isolates of serotypes Bovis-morbificans, Cholerae-suis and Enteritidis
      phage type 9b hybridized pefA strongly, whereas 48 isolates of Enteritidis
      hybridized pefA weakly and one Enteritidis isolate of phage type 14b failed to
      hybridize. Individual isolates of 294 serotypes and 247 individual isolates of
      serotype Dublin did not hybridize pefA. Southern hybridization of plasmids
      extracted from Enteritidis demonstrated that the pefA gene probe hybridized
      strongly an atypical SAP of 80 kb in size harboured by one Enteritidis isolate of
      phage-type 9b, whereas the typical SAP of 58 kb in size harboured by 48
      Enteritidis isolates hybridized weakly. One Enteritidis isolate of phage type 14b
      which failed to hybridize pefA in dot (colony) hybridization experiments was
      demonstrated to be plasmid free. A cosmid library of Enteritidis phage type 4
      expressed in Escherichia coli K12 was screened by hybridization for the presence
      of pef sequences. Recombinant clones which were deduced to harbour the entire pef
      operon elaborated a PEF-like fimbrial structure at the cell surface. The PEF-like
      fimbrial antigen was purified from one cosmid clone and used in western blot
      experiments with sera from chickens infected with Enteritidis phage-type 4.
      Seroconversion to the fimbrial antigen was observed which indicated that the
      Enteritidis PEF-like fimbrial structure was expressed at some stage during
      infection. Nucleotide sequence analysis demonstrated that the pefA alleles of
      Typhimurium and Enteritidis phage-type 4 shared 76% DNA nucleotide and 82%
      deduced amino acid sequence identity.

PMID- 8760948
TI  - Salmonella virchow PT 26 infection in England and Wales: a case control study
      investigating an increase in cases during 1994.
AB  - An increase in the number of human isolates of Salmonella virchow phage type (PT)
      26 in England and Wales during 1994 was investigated. A national case control
      study was conducted which included 88 cases and 182 controls. The cases were
      mostly young adults (median age 26) and 13 (15%) were admitted to hospital.
      Acquisition of S. virchow PT 26 was associated with the consumption of any
      chicken (OR 2.5, CI 1.1-5.8), of chicken curry from restaurants and take aways
      (OR 2.9, CI 1.4-6.1), and of some other diverse types of pre-prepared chicken (OR
      3.8, CI 1.9-7.6). Halal chicken was associated (P = 0.006) with illness in a
      subset. There were negative associations with contact with animals (OR 0.47, CI
      0.23-0.95) and with the consumption of chicken cooked whole (OR 0.37, CI 0.21
      0.66). The increase in S. virchow PT 26 may be due to changing epizoology and may
      be an indicator of what will become the dominant salmonella strain in poultry in
      future years. The increasing incidence of S. virchow PT 26 is of particular
      concern because of its association with more invasive disease in humans.

PMID- 8760949
TI  - Resurgence of cholera in Hong Kong.
AB  - Cholera is one of the three diseases subject to the International Health
      Regulations. After a period of over 30 years, the seventh pandemic of cholera,
      which started in South East Asia in 1961, still shows no sign of a decline. On
      the contrary, it has increased its severity and invaded many other countries in
      Africa and Latin America. In the last two years, there has been a recrudescence
      of the disease in South East Asia and Western Pacific Regions. The discovery of a
      new strain of Vibrio cholerae 0139 in these regions is causing concern in view of
      its potential to cause major epidemics and higher mortality. Hong Kong had two
      intensive outbreaks of cholera in the last two years. The cause of these
      outbreaks was not clear, but adverse environmental conditions and increasing
      pollution of coastal waters have been implicated. The spread of cholera knows no
      geographical boundaries. There is a need for intensified efforts among health
      authorities in the affected areas to prevent the international spread of the
      disease.

PMID- 8760950
TI  - Comparison of pulsed-field gel electrophoresis and ribotyping for subtyping of
      Vibrio cholerae O139 isolated in Thailand.
AB  - Pulsed-field gel electrophoresis (PFGE) of Cpo I-digested genomic DNA and
      ribotyping (Bgl I) were applied to 60 Vibrio cholerae strains including 48 V.
      cholerae O139 from Thailand to compare their value in differentiating strains of
      the present V. cholerae O139 epidemic. PFGE patterns were divided into groups A
      and B representing five and four subtypes, respectively, while ribotyping showed
      four different patterns. PFGE group B subtypes were only presented among O139
      isolates from Thailand, whereas four O139 strains from Bangladesh and India
      showed identical PFGE group A subtypes observed in O139 isolates from Thailand.
      Two nontoxigenic O139 isolates from Thailand showed different and unique PFGE
      types as did five V. cholerae non-O139 isolates containing a gene virulence
      complex found in V. cholerae O139. These results indicate that PFGE (Cpo I) can
      resolve recent evolutionary divergence within V. cholerae O139 and offers a
      useful supplementary tool for following the progressing V. cholerae O139
      epidemic.

PMID- 8760951
TI  - Detection of pathogenic Yersinia enterocolitica using the multiplex polymerase
      chain reaction.
AB  - A multiplex polymerase chain reaction (PCR) was developed to detect the presence
      of the ail, yst, and virF genes of Yersinia enterocolitica simultaneously,
      quickly and accurately. The amplified fragment sizes were 356 base-pairs (bp) for
      the ail gene, 134 bp for the yst gene, and 231 bp for the virF gene. The
      specificity of the amplified products was confirmed by hybridization with
      digoxigenin-labelled oligonucleotide probes. Amplification was successful whether
      the template was derived from a single colony of bacteria, aliquots of boiled
      bacterial suspensions, from DNA extracted from pure or mixed cultures or from
      stool specimens. Amplification of the virF gene was also achieved from strains of
      Y. pseudotuberculosis carrying the 70 kb plasmid but not with preparations from
      other related Yersinia species or from other members of the family
      Enterobacteriaceae. The detection limit we established was 5-10 colony forming
      units per millilitre (cfu/ml) and 1.0 pg of DNA.

PMID- 8760952
TI  - World Health Organisation--supervised interlaboratory comparison of ELISAs for
      the serological detection of Salmonella enterica serotype Enteritidis in
      chickens.
AB  - A collaborative exercise, supervised by the World Health Organisation, was set up
      to compare ELISAs used for the serological detection of Salmonella enteritica
      serotype Enteritidis in chickens. The aim was to ascertain how far agreement
      could be reached on the interpretation of optical density readings for high
      titre, intermediate titre and low titre sera. Two sets of sera were sent to 14
      participants. The first set compared high, medium and low titre sera raised in
      specified-pathogen-free and commercial broiler breeder chickens. The second set
      comprised 20 sera of different antibody titres raised in commercial birds reared
      under laboratory conditions and sent blind. Both indirect and double-antibody
      sandwich blocking ELISAs were used with a number of different detecting antigens.
      With a few exceptions good agreement was reached on the interpretation of results
      obtained from high and low titre sera from the optical density obtained with a
      single serum dilution. Differences were observed in the interpretation of medium
      titre sera. The results suggested that most ELISAs produce reasonably comparable
      results and that practical problems may arise from interpretation of the results
      mainly as a result of the choice of the criteria used for differentiating sera
      obtained from infected and uninfected chickens. These problems are discussed.

PMID- 8760954
TI  - Occurrence of Listeria species in prepacked retail sandwiches.
AB  - A survey of 725 prepacked sandwiches was conducted examining for the presence on
      enrichment, and by plate count, of Listeria species. Sandwiches were found to
      contain Listeria sp. more frequently than their component foods. Chicken, beef
      and bacon fillings were associated with more frequent isolation. Salad also was
      associated with more frequent isolation, but the increase was not significant. On
      enrichment, over 15% of sandwiches contained Listeria species. L. innocua and L.
      monocytogenes were the only species isolated by plate count at numbers > or = 100
      cfu/g (1.5% of total samples). Potentially hazardous levels of L. monocytogenes
      (defined as > or = 10(3) cfu/g) were found in two sandwiches examined (0.3%),
      indicating that although Total Viable Counts (TVCs) may often be high, the risk
      of listeriosis to vulnerable individuals from sandwiches is relatively low. It is
      important to distinguish the risk of consuming potentially hazardous levels of a
      pathogen in food from the risk of contracting illness as a result of such an
      event.

PMID- 8760953
TI  - Isolates of Salmonella enterica Enteritidis PT4 with enhanced heat and acid
      tolerance are more virulent in mice and more invasive in chickens.
AB  - Two Enteritidis PT4 isolates which differed in inherent tolerance to heat, acid,
      H2O2 and the ability to survive on surfaces were used to infect mice, day-old
      chicks or laying hens. The acid-, heat-, H2O2- and surface-tolerant isolate was
      more virulent in mice and more invasive in laying hens, particularly in
      reproductive tissue. However, no significant differences were observed in
      behaviour in chicks. Both PT4 isolates were able to infect chicks housed in the
      same room as infected birds, although the heat-tolerant isolate survived
      significantly better than the heat-sensitive one in aerosols.

PMID- 8760955
TI  - Pneumococcal meningitis in the North East Thames Region UK: epidemiology and
      molecular analysis of isolates.
AB  - One hundred and fourteen cases of pneumococcal meningitis were identified by
      prospective laboratory based surveillance during 1990-3 in the North East Thames
      Region. Higher rates of disease were seen in Asians (2.1/100000) than Caucasians
      (0.8/100000) (P = 0.002). The incidence of meningitis was higher in children than
      adults, while mortality rates were highest in adults over the age of 60 (48%). In
      72 cases, both blood and CSF were culture positive. Serotyping of 65 isolates
      collected identified 22 serotypes (and one non-typable) causing disease, the most
      common being serotype 6 (13 cases) and serotype 14 (11 cases). Overall, 90% of
      serotype antigens identified were represented in the 23 valent vaccine.
      Ribotyping of 62 isolates identified 35 different patterns, of which 26 were
      single types. Different ribotypes were found among isolates of the same
      serotypes, with the exception of serotype 14, where 9 of 11 isolates had the same
      ribotype pattern. Four percent of isolates had reduced susceptibility to
      penicillin, but no high level penicillin resistance was found.

PMID- 8760956
TI  - Antibiotic prescribing during an outbreak of meningococcal disease.
AB  - During a prolonged outbreak of meningococcal disease caused by serogroup B
      serotype 15 sulphonamide-resistant strains in one British health district, there
      was considerable variation in attack rates by town. General practitioner (GP)
      antibiotic prescribing rates were compared in high and low incidence towns. The
      only significant difference found was that erythromycin prescribing was more
      frequent in the high incidence towns (rate ratio 4.0, 95% CI 3.2-4.8, in March
      1987 and 3.0, 95% CI 2.4-3.7, in November 1987). This was probably due to
      increased GP consultation rates for upper respiratory tract infection (URTI), but
      higher erythromycin usage may have increased meningococcal acquisition rates or
      susceptibility to meningococcal disease. Antibiotic prescribing rates should be
      further investigated in defined areas of high and low incidence of meningococcal
      disease.

PMID- 8760957
TI  - Respiratory syncytial virus infection and meningococcal disease.
AB  - Although viral respiratory tract infections may predispose to meningococcal
      disease, strong evidence that they do so exists only for influenza. Data on
      laboratory reported cases of respiratory syncytial virus (RSV) infections and
      meningococcal disease in England and Wales from mid-1989 to mid-1994 were
      analysed. Although the rise in RSV cases preceded the rise in meningococcal
      disease cases each winter, the interval between the rise and fall of the two
      diseases was inconsistent, no association was found between time series after
      removal of the seasonal component, and there was no evidence that more cases of
      meningococcal disease occurred in winters with more RSV disease. RSV may have
      less effect on the two most likely mechanisms whereby influenza predisposes to
      meningococcal disease, namely lowered immunity and impaired pharyngeal defences.

PMID- 8760958
TI  - Iatrogenic outbreak of M. chelonae skin abscesses.
AB  - We describe an outbreak of skin lesions due to Mycobacterium chelonae subsp.
      abscessus associated with injections of lidocaine (lignocaine) given by a
      'bioenergetic' (a practitioner of alternative medicine) in Colombia. The
      lidocaine carpules and the lesions of the patients yielded mycobacteria with
      identical biochemical characteristics. Using the methodology of Sartwell and a
      case control design we examined the incubation period and assessed risk factors.
      Of 667 potentially exposed individuals, a total of 298 patients were interviewed,
      of whom 232 had skin lesions. The median incubation period was 30.5 days (range
      15-59 days). Male sex (OR 2.85, 95% CI 1.26-6.51), increasing age (OR 1.25, 95%
      CI 1.03-1.53), subcutaneous injection route (OR 3.72, 95% CI 1.09-12.7) and
      number of injections (OR 1.01, 95% CI 1.00-1.03) were risk factors for disease.
      To our knowledge, this is the largest reported outbreak of M. chelonae infection,
      the first in which the organism has been isolated from the putative vehicle of
      infection, and the first in which the incubation period could be determined.

PMID- 8760959
TI  - Ante-natal screening for hepatitis B surface antigen: an appraisal of its value
      in a low prevalence area.
AB  - The costs and projected benefits of universal screening for hepatitis B virus
      (HBV) infection in pregnant women in East Anglia are calculated and compared with
      current practice. By adjusting data from West Midlands region for ethnicity, the
      prevalence of maternal hepatitis B surface-antigen (HBsAg) positivity in East
      Anglia is predicted to be 0.083% (1 in 1200). Published data on health risks of
      perinatal HBV infection and on immunisation efficacy are used to derive benefits
      of screening. The marginal direct cost of screening is identified from regional
      sources. Current clinical practice in East Anglia identifies 7 surface-antigen
      positive mothers per year, whereas 22 are expected. Routine antenatal screening
      in East Anglia would prevent 2.6 additional childhood carriers per year (compared
      with current practice), resulting in the prevention of 0.7 deaths per year
      occurring 40-50 years in the future. The direct cost per (undiscounted) life-year
      saved would be Pounds 2437, not including savings on treatment for chronic
      hepatitis B infection. Routine prenatal screening for maternal HBsAg should be
      introduced without delay and continue even if HBV vaccination is introduced into
      the UK childhood immunisation schedule.

PMID- 8760960
TI  - Hepatitis B virus infection in general population in Madagascar: evidence for
      different epidemiological patterns in urban and in rural areas.
AB  - To describe the features of hepatitis B virus (HBV) infection in Madagascar, a
      randomized sero-epidemiological survey was undertaken in the general population >
      or = 1 year old of two provinces which represents 45% of the total population. In
      the 921 sera tested, the prevalence of HBV markers was 20.5% for HBsAg, 38.2% for
      anti-HBc and 6.9% for HBeAg. HBsAg and anti-HBc prevalence rates were
      significantly higher in males. A large difference in HBsAg prevalence was
      observed between urban (5.3%) and rural areas (26.0%). The same contrast in
      prevalence was noticed for the other HBV markers. In rural areas, HBV infection
      was more frequently acquired early in infancy, which suggests predominantly
      perinatal or postnatal transmission. The presence of HBV markers was not
      significantly associated with a history of blood transfusion, surgery or
      parenteral injection. High infectivity carriers represented 5.3% and the overall
      frequency of chronic carriers was 10.4%. These results place Madagascar among
      areas of high endemicity.

PMID- 8760962
TI  - Are homosexual males a risk group for hepatitis A infection in intermediate
      endemicity areas?
AB  - The purpose of this study was to examine the prevalence of antibody against
      hepatitis A (anti-HAV) in a population of homosexual men compared with that of
      heterosexual men in an area of intermediate HAV endemicity (Madrid, Spain). A
      total of 148 patients were recruited in a Sexually Transmitted Diseases Clinic:
      74 homosexuals (mean age of 28 +/- 5 years) and 74 heterosexuals (29 +/- 5
      years). The prevalence of anti-HAV antibody was 47% and 43% for homo- and
      heterosexuals, respectively. Among the factors evaluated (age, sexual orientation
      and practices, travel to high HAV endemicity areas) oral-anal contact was
      significantly associated with a higher prevalence of anti-HAV antibody (odds
      ratio, 2.8; 95% confidence interval, 1.1-7.4; P = 0.03). These results indicated
      that in an area of intermediate endemicity young homosexual men are not at
      increased risk of having acquired hepatitis A infection than heterosexuals. Oral
      anal contact is an independent risk factor that influences the presence of anti
      HAV antibody, regardless of sexual orientation.

PMID- 8760961
TI  - Microbiology of HIV associated bacteraemia and diarrhoea in adults from Nairobi,
      Kenya.
AB  - We undertook a retrospective descriptive comparison of the spectrum of pathogens
      responsible for bacteraemia and diarrhoea in HIV antibody positive and negative
      patients over 4 years (1988-92), in Nairobi, Kenya. The study population was
      recruited from primary to tertiary centres of clinical care and consisted of 2858
      adults (15 years or older). There were 415 significant blood culture isolates,
      192 from 1785 HIV negative patients and 223 from 953 HIV positive patients. There
      were 233 significant faecal isolates, 22 from 115 HIV negative patients and 211
      from 531 HIV positive patients. The most common pathogens detected in blood were
      Streptococcus pneumoniae and Salmonella typhimurium and in faeces Shigella
      flexneri, S. typhimurium and Cryptosporidium parvum. The agents causing illness
      in HIV positive patients in Nairobi are similar to those prevalent in the HIV
      negative community and the investigation of a febrile illness with or without
      diarrhoea in an HIV positive patient should reflect this.

PMID- 8760963
TI  - Outbreak of vertigo in Wyoming: possible role of an enterovirus infection.
AB  - An epidemiologic investigation was conducted to characterize and evaluate the
      possibility of a viral aetiology of an outbreak of acute vertigo in Hot Springs
      Country, Wyoming, during autumn 1992. Case-finding identified Hot Springs County
      residents who sought medical attention for new onset vertigo during 1 August,
      1992-31 January 1993. Thirty-five case-patients and 61 matched controls were
      interviewed and serum specimens were obtained during January 1993. Case-patients
      were more likely than controls to report symptoms (e.g. fatigue, sore throat,
      fever, diarrhoea) of antecedent acute illness. Case-patients did not have a
      significantly greater prevalence or mean titre of IgG antibodies to respiratory
      syncytial virus, parainfluenza viruses, Epstein-Barr virus, and cytomegalovirus
      than controls. Serologic evidence of recent enterovirus infection (IgM
      antibodies) was found for 74% of case-patients compared with 54% of controls (P <
      0.05), suggesting a possible association between vertigo and enterovirus
      infection. Future studies are needed to define the role of enteroviruses in
      innerear diseases.

PMID- 8760964
TI  - Seroprevalence of astrovirus types 1 and 6 in London, determined using
      recombinant virus antigen.
AB  - We have developed a microimmunofluorescence test (IF) which uses cells infected
      with a recombinant baculovirus which expresses the capsid proteins of astrovirus
      types 1 or 6. The IF test was sensitive and specific and the results for human
      astrovirus type 1 (HAst-1) were comparable to those obtained by immune
      electronmicroscopy and radioimmunoassay. Application of the test to a panel of
      273 sera collected from patients and staff at two childrens hospitals in London
      showed that over 50% of the population were infected by HAst-1 between the age of
      5 and 12 months rising to 90% by 5 years, whereas human astrovirus type 6 (HAst6)
      was relatively uncommon (10-30%) in all age groups.

PMID- 8760965
TI  - An analysis of infection control of varicella-zoster virus infections in
      Addenbrooke's Hospital Cambridge over a 5-year period, 1987-92.
AB  - This prospective study analyses infections with varicella-zoster virus (VZV) in
      Addenbrooke's Hospital, Cambridge during 1987-92 and examines the spread of
      infection. In total, 93 patients and staff experienced VZV infection. Twenty-one
      patients had varicella and 49 experienced zoster. None of 101 patients and 1 of
      625 staff members in contact with varicella cases acquired infection. By
      contrast, 2 of 227 patients, and 5 of 1039 staff in contact with zoster cases
      acquired varicella. One out of 28 (3.6%) VZV antibody-negative patients and staff
      in contact with varicella acquired infection, compared with 5 out of 29 (17.2%)
      VZV antibody-negative patients and staff in contact with zoster. Thus, zoster was
      found to be a more frequent cause of nosocomial infection than varicella.
      Fourteen members of staff had VZV infection during the study period. One of 99
      patients and none of 389 staff members in contact with these cases developed
      varicella. The cost of dealing with infection control for VZV infections in our
      hospital is estimated to be Pounds 714 per patient case and a total of Pounds
      13,204 per year.

PMID- 8760966
TI  - Impact of incomplete coverage of neonatal dried blood spot screening on
      estimating HIV-1 seroprevalence.
AB  - The aim of this study was to determine the extent to which selective under
      coverage of births to mothers more likely to be at risk of HIV-1 infection will
      result in a significant under-estimation of the true neonatal seroprevalence.
      Census data, local birth statistics, maternity data and data from the prevalence
      monitoring programme were used to produce a model to predict the effects of under
      coverage in the uptake of neonatal metabolic screening which has been observed in
      babies with a mother of ethnic group black African. The adjustment factor which
      allows for under-coverage is the relative inclusion ratio (RIR); the probability
      that samples from a group at different risk of HIV infection were included in the
      survey divided by the probability of inclusion for samples from all other babies.
      The RIR was found to be close to unity (0.97), indicating a minimal bias. Under
      usual conditions only if the relative inclusion ratio (RIR) declined to values of
      0.87 or below would there be a substantial bias. Despite some selective under
      representation, the results obtained from the Unlinked Anonymous HIV Monitoring
      Programme Dried Blood Spot Survey would seem to identify levels of prevalence in
      the population of child-bearing women with a good degree of accuracy and remains
      a useful tool for resource allocation, planning of services, provision of care
      and counselling.

PMID- 8760968
TI  - The incidence of Cyclospora cayetanensis in stool samples submitted to a district
      general hospital.
AB  - Cyclospora cayetanensis is the cause of a prolonged diarrhoeal syndrome. In the
      UK most cases are seen in travellers who have returned from countries in which
      the organism is endemic. The purpose of this investigation was to determine the
      incidence of C. cayetanensis in stool samples submitted to a district general
      hospital. A total of 6151 stools from 5374 different patients were screened for
      the presence of C. cayetanensis over a 1-year period using the modified Ziehl
      Neelsen technique. Oocysts of C. cayetanensis were found in 7 stools (0.1%) from
      4 patients (0.07%). All four patients were adult travellers who had visited
      countries in which C. cayetanensis is known to be endemic. In the population of
      this study, C. cayetanensis was found to be a rare cause of diarrhoea. Although
      C. cayetanensis infection should be considered in individuals of all ages who
      have lived in, or have travelled to endemic areas, there is no need to screen
      stool samples for the organism in those without such a travel history.

PMID- 8760967
TI  - An epidemiological study of influenza viruses among Chinese farm families with
      household ducks and pigs.
AB  - To examine the possibility of interspecies transmission and genetic reassortment
      of influenza viruses on farms in Southern China, we surveyed 20 farm families
      living outside the city of Nanchang who raised pigs and ducks in their homes.
      Weekly interviews of family members and virus isolation studies of throat swabs
      and faecal samples, collected from September 1992 to September 1993, established
      the seasonal pattern of respiratory tract infections in these families and
      identified 11 influenza viruses (6 in humans and 5 in ducks). Most of the human
      isolates were type A of H3N2 subtype. Serologic studies of farm pigs indicated
      infection by the same human viruses circulating in family members, but there was
      no evidence that either swine or avian viruses had been transmitted to pigs.
      Eight of 156 human serum samples inhibited the neuraminidase activity of two of
      the duck isolates, raising the possibility of interspecies transmission of these
      avian viruses. Genotype analysis of duck and human isolates provided no evidence
      for reassortment. Our finding support the concept that intermingling of humans,
      pigs and ducks on Chinese farms is favourable to the generation of new,
      potentially hazardous strains of influenza virus.

PMID- 8760969
TI  - Past exposure and the dynamics of lymphatic filariasis infection in young
      children.
AB  - This study utilizes parallel, longitudinal entomological and parasitological data
      collected during a 5-year vector control programme in Pondicherry, South India,
      to quantify Wuchereria bancrofti transmission from the vector to the human
      population. A simple mathematical model, derived from the standard catalytic
      model, is used to examine the hypothesis that current infection prevalence in
      young children is a dynamical function of their cumulative past exposure to
      infective bites. Maximum likelihood fits of the model to the observed data
      indicate a constant child infection rate with age, above a threshold representing
      the pre-patent period, or equivalently, the cumulative biting intensity required
      to produce patent infections. Extrapolation of the model allows the crude
      estimation of the equilibrium microfilaria age-prevalence curve due to control.
      The results suggest that vector control alone may have little impact on the
      overall age-prevalence of infection even when sustained for long periods. These
      observations are discussed in terms of the likely impact of density dependent
      mechanisms, such as acquired immunity, on model predictions.

PMID- 8760970
TI  - Role of enteric pathogens in the aetiology of neonatal diarrhoea in lambs and
      goat kids in Spain.
AB  - Faeces samples from diarrhoeic and non-diarrhoeic lambs and goat kids aged 1-45
      days were examined for enteric pathogens. Cryptosporidium parvum was detected in
      both diarrhoeic lambs (45%) and goat kids (42%) but not in non-diarrhoeic
      animals. F5+ (K99+) and/or F41+ Escherichia coli strains were isolated from 26%
      and 22% of the diarrhoeic lambs and goat kids, respectively, although these
      strains, which did not produce enterotoxins ST I or LT I, were found with similar
      frequencies in non-diarrhoeic animals. A F5-F41-ST I+ E. coli strain was isolated
      from a diarrhoeic lamb (0.6%). Verotoxigenic E. coli was isolated from both
      diarrhoeic and non-diarrhoeic lambs (4.1% and 8.2%, respectively) and there was
      no association between infection and diarrhoea. The prevalence of group A
      rotavirus infection in diarrhoeic lambs was very low (2.1%). Groups A and B
      rotaviruses were detected in three (8.1%) and five (13.5%) diarrhoeic goat kids
      from two single outbreaks. Group C rotaviruses were detected in four non
      diarrhoeic goat kids. An association of diarrhoea and infection was demonstrated
      only for group B rotavirus. Clostridium perfringens was isolated from 10.8% of
      the diarrhoeic goat kids but not from non-diarrhoeic goat kids or lambs.
      Salmonella arizonae was isolated from a diarrhoeic goat kid (2.7%) and the
      clinical characteristics of the outbreaks where these two latter enteropathogens
      were found different from the rest. Picobirnaviruses were detected in a
      diarrhoeic lamb. No coronaviruses were detected using a bovine coronavirus ELISA.
      No evidence was found of synergistic effect between the agents studied. Enteric
      pathogens were not found in four (8.7%) and three (20%) outbreaks of diarrhoea in
      lambs and goat kids, respectively.

PMID- 8760971
TI  - Increased colonization potential of Campylobacter jejuni strain 81116 after
      passage through chickens and its implication on the rate of transmission within
      flocks.
AB  - The mechanisms by which Campylobacter jejuni rapidly spreads through large
      broiler flocks are unknown. Recent evidence suggests that the minimum infective
      oral dose for 100% caecal colonization is about 10(4) cfu, which, with such a
      'fragile' organism, may limit transmissibility. However, the colonization
      potential of laboratory-adapted strains may be anomalous compared with fresh
      isolates or those passaged in vivo. The colonization potential of two chicken and
      one human C. jejuni isolates, which were minimally passaged, have been
      investigated using a quantitative model of chicken colonization. There was no
      detectable difference between these strains but all were more efficient
      colonizers than a laboratory-adapted strain 81116. In addition, the colonization
      potential of C. jejuni strain 81116 following a passage in vivo was also
      determined. The results indicated this increased c. 10000 fold following a single
      passage in vivo, such that a dose of only 40 cfu caused maximal colonization.
      Enhanced colonization potential may, therefore, account for the rapid rate of
      transmission within large flocks.

PMID- 8760972
TI  - Recommendations for the management of chronic critical lower limb ischaemia. The
      Audit Committee of the Vascular Surgical Society of Great Britain and Ireland.

PMID- 8760973
TI  - Refinements of the in situ vein bypass: towards a more "closed" technique.

PMID- 8760974
TI  - Incidence and clinical presentation of bowel ischaemia after aortoiliac surgery-
      2930 operations from a population-based registry in Sweden.
AB  - OBJECTIVES: To study the incidence and clinical presentation of intestinal
      ischaemia after aortoiliac/femoral surgery, and to validate a vascular registry
      concerning a serious complication. DESIGN AND SETTING: In the Swedish Vascular
      Registry (SWEDVASC) the outcome and complications of all vascular procedures are
      registered prospectively. MATERIALS AND METHODS: All 2930 patients operated in
      1987-93 were analysed for notified complications. A 5% random sample of all
      patients and a 20% random sample of fatal cases were analysed for un-notified
      complications. Of 415 requested patient records 413 were analysed. RESULTS: The
      estimated incidence of bowel ischaemia was 2.8%. Among patients operated on for a
      ruptured aneurysm in shock it was 7.3%. Of the 63 patients with intestinal
      ischaemia only 15 presented with early passage of bloody stools. In 60 patients
      (95%) the lesion affected the left colon within the reach of a sigmoidoscope.
      Bowel ischemia was unnotified only in fatal cases, the estimated un-notified
      complication rate was 0.7%. CONCLUSIONS: The incidence in this study on
      unselected patients did not differ from previous reports from specialised
      centres. Diagnosis is difficult and justifies a high index of suspicion and early
      use of sigmoidoscopy. The validity of the SWEDVASC registry was confirmed by a
      high report-rate for this complication.

PMID- 8760975
TI  - The value of duplex surveillance after endovascular intervention for
      femoropopliteal obstructive disease.
AB  - OBJECTIVE: The objective of the present study was to assess prospectively whether
      serial Duplex examination was useful in identifying impending failure after
      endovascular interventions of the femoropopliteal arteries. SETTING: Non
      university hospital. Prospective clinical study. METHODS: 124 Patients were
      successfully treated by endovascular procedures during a 5 year period. The
      follow-up was by colour-flow Duplex examination at fixed intervals. At similar
      intervals clinical examination, including ankle blood pressure measurement was
      performed to assess the clinical/haemodynamic status of the patients according to
      the SVS/NAISCVS guidelines. For the diagnosis of impending failure the Duplex
      criterion was a peak systolic velocity ratio > 2.5 and the clinical/haemodynamic
      criterion was a level < +2. Actual failure of the vascular procedure was defined
      as the occurrence of an occlusion in the treated arterial segment or a recurrent
      stenosis causing symptoms severe enough to require a reintervention. No
      prophylactic reinterventions were performed on the basis of abnormal Duplex
      findings alone. RESULTS: Abnormal Duplex findings indicating restenosis were
      observed in 52 patients. Duplex abnormalities predicted treatment failure with a
      sensitivity of 86% and a specificity of 75%, while clinical/haemodynamic
      assessment had a sensitivity of 93% and a specificity of 90%. The hypothetical
      management outcome if Duplex surveillance had been used as a basis for
      reintervention was assessed. It appeared that only one patient with failure would
      have received a redo endovascular procedure at the time he had a restenosis.
      CONCLUSIONS: Clinical/haemodynamic assessment was more useful for the follow-up
      of endovascular interventions than Duplex surveillance.

PMID- 8760976
TI  - Characterisation of angiotensin II receptor mediated responses and inhibition of
      intimal hyperplasia in experimental vein grafts by the specific angiotensin II
      receptor inhibitor, L158,809.
AB  - OBJECTIVES: This study characterises pharmacologically the angiotensin II
      receptor in experimental vein grafts and examines the effect of the angiotensin
      II receptor (type 1) antagonist (L158,809) on the formation of vein graft intimal
      hyperplasia in vivo, as well as the in vitro physiological response to
      angiotensin II of vein grafts after chronic oral L158,809 treatment. MATERIALS:
      Thirty New Zealand White rabbits had a right carotid interposition bypass graft
      using the external jugular vein and were killed on the 28th postoperative day.
      DESIGN: To characterise the angiotensin II receptors, concentration response
      curves to angiotensin II were obtained in vitro in the presence or absence of
      L158,809. To determine the effect of L158,809 on the development of intimal
      hyperplasia, 10 animals received chronic oral therapy with L158,809 (10
      mg/kg/day; begun 5 days before surgery and continued until harvest) and 10
      animals received vehicle only as controls. These grafts were harvested either for
      histology (n = 6 per group) or for in vitro isometric tension studies to
      angiotensin II. RESULTS: The monophasic contractile response to angiotensin II in
      the untreated vein grafts could be inhibited in a concentration dependent manner
      by L158,809 with first order kinetics. Chronic oral treatment with L158,809
      produced a 48% decrease in intimal thickness from 82 +/- 1 micron (mean +/-
      S.E.M.) in the controls to 43 +/- 7 microns in the treated vein grafts (p =
      0.002). There was also a significant decrease (45%) in the medial thickness
      between the control (76 +/- 6 microns) and L158,809 treated (42 +/- 6 microns)
      vein grafts (p = 0.007). The responses to angiotensin II were abolished in the
      vein grafts by chronic L158,809 therapy. CONCLUSIONS: This study suggests that
      vein graft angiotensin II responses are mediated through a type 1 receptor and
      that chronic inhibition with L158,809, significantly reduces intimal hyperplasia
      and medial hypertrophy in experimental vein grafts and concomitantly abolishes
      the in vitro responses to angiotensin II. Therefore, angiotensin II acting
      through AT1 receptors mediates a significant part of the intimal hyperplastic
      response in vein grafts.

PMID- 8760977
TI  - Unravelling the familial tendency to aneurysmal disease: popliteal aneurysm,
      hypertension and fibrillin genotype.
AB  - PURPOSE: To screen patients with abdominal aortic aneurysm for popliteal aneurysm
      and investigate cardiovascular and genetic risk factors associated with
      aneurysmal disease at more than one site (generalised aneurysmal disease).
      SUBJECTS, DESIGN AND SETTING: All patients referred to the Regional Vascular
      Surgical Service at Charing Cross Hospital with unruptured abdominal aortic
      aneurysm between 1989 and 1993 were screened for popliteal aneurysms, using
      ultrasonography. MAIN OUTCOME MEASURES: Palpation of a popliteal aneurysm or
      ultrasonographic detection of popliteal dilatation, where the ratio maximum
      popliteal fossa diameter/suprageniculate popliteal diameter was > or = 1.5, in
      relation to cardiovascular and genetic risk factors. RESULTS: Clinical
      examination detected popliteal aneurysms in only 11/232 patients (5%), but
      ultrasonography demonstrated the presence of popliteal aneurysm in a further 13
      patients, 24/232 in total (10%). Multivariate regression identified four
      independent factors associated with popliteal dilatation disease: age (p =
      0.046), height (p = 0.006), systolic hypertension (p = 0.037) and triglyceride
      concentration (p = 0.009). Generalised aneurysmal disease and systolic blood
      pressure were associated with polymorphic variation in the fibrillin-1 gene, but
      not with variations in the apolipoprotein B and type III collagen genes.
      CONCLUSIONS: Few patients with abdominal aortic aneurysm (10%) also have
      popliteal aneurysms: the risk of popliteal dilatation increases with age, height,
      systolic blood pressure, triglyceride concentration and fibrillin genotype. The
      strong interaction between fibrillin genotype and blood pressure may contribute
      to the familial tendency to aortic aneurysm.

PMID- 8760978
TI  - Randomised controlled trial of percutaneous transluminal angioplasty for
      intermittent claudication.
AB  - OBJECTIVES: To determine differences between PTA and conventional medical
      treatment in treadmill distance until onset of claudication, treadmill maximum
      walking distance, patient reported maximum walking distance, ankle brachial
      pressure index (ABPI), quality of life (Nottingham Health Profile, NHP) and
      Duplex measured extent of occlusive disease. DESIGN: Randomised controlled
      clinical trial. METHODS: Six hundred claudicants were screened. Fifty-one men and
      11 women with intermittent claudication due to short femoral stenoses or
      occlusions (n = 47) and iliac stenoses (n = 15) were randomised to either PTA
      plus medical treatment (PTA group, n = 30) or to medical treatment alone (control
      group, n = 32). Medical treatment consisted of daily low dose aspirin and advice
      on smoking and exercise. RESULTS: At 6 month follow up: In the PTA group more
      patients reported no claudication (p < or = 0.05) and were asymptomatic on the
      treadmill (p < or = 0.01) compared to the control group. The ABPI was
      significantly higher in the PTA group. More of the PTA group reported lower NHP
      pain scores (p < or = 0.05). In the control group there were more occluded
      arteries (p < or = 0.001), and the stenosis velocity ratio of patient arteries
      was significantly higher (p < or = 0.001). CONCLUSIONS: Only 10% of claudicants
      had discrete lesions suitable for PTA. Treatment of these patients with PTA
      produces a greater short-term improvement in walking and quality of life than
      medical treatment alone and is associated with less progression of disease.

PMID- 8760979
TI  - The differing effects of regional and general anaesthesia on cerebral metabolism
      during carotid endarterectomy.
AB  - OBJECTIVES: To examine the effects of either regional (RA) or general (GA)
      anaesthesia upon parameters of cerebral metabolism (near infrared spectroscopy,
      continuous jugular venous oximetry) during carotid endarterectomy. DESIGN:
      Prospective, non-randomised, observational study. MATERIALS: Sixty-five
      consecutive patients (33 RA; 32 GA) undergoing carotid endarterectomy. METHODS:
      (i) Near infrared spectroscopy: measurement of concentrations of cerebral
      oxyhaemoglobin (HbO2), deoxyhaemoglobin (HHb) and oxidised cytochrome oxidase
      (caa3). (ii) Continuous jugular venous oximetry: O2 saturation of jugular venous
      blood (SJvO2). (iii) Stump pressure in internal carotid artery. RESULTS: A
      reduction in SJvO2 (RA: 13% (95% CI-3 to 29%) GA: 9% (95% CI-2 to 20%), p < 0.08)
      and a fall in caa3 levels (RA vs. GA: 25/31 vs. 19/31, p = 0.2) was more likely
      in patients given a RA following application of the carotid clamps. When HbO2 and
      caa3 did fall however spontaneous recovery occurred more often (RA vs. GA; caa3:
      18/25 vs. 5/19, p < 0.005; HbO2: 30/31 vs. 4/28, p < 0.001). CONCLUSIONS:
      Although GA may offer a degree of cerebral protection by reducing cerebral
      metabolic rate (lower falls in SJvO2 and caa3) RA preserved cerebral
      autoregulation as judged by the spontaneous recovery in caa3 and HbO2 levels.

PMID- 8760980
TI  - CT-angiography of abdominal aortic aneurysms after transfemoral endovascular
      aneurysm management.
AB  - OBJECTIVE: To evaluate short-term effect of Transfemoral Endovascular Aneurysm
      Management (TEAM) on aortic diameters and volumes after aneurysm exclusion, using
      CT-angiography. DESIGN: Analysis of preoperative, 1 week postoperative and 6
      months postoperative CT measurements. SETTING: University Hospital. MATERIALS:
      Nine patients treated with an endovascular tube prosthesis. CHIEF OUTCOME
      MEASURES: True cross-sectional diameters of the aorta and the aneurysm, volume of
      the infrarenal aortic lumen, of the thrombus and of the iliac arteries and length
      of the aorta and of the endovascular prosthesis. MAIN RESULTS: CT-angiography
      detected shrinkage of the aneurysm in seven patients. Aneurysm growth was
      observed in one patient with persistent flow outside the graft and in one patient
      with fully thrombosed aneurysm sac. In the two patients with increasing thrombus
      volume, the volume of the aortic lumen decreased. CONCLUSIONS: Although
      successful aneurysm exclusion can be confirmed by maximum aneurysm diameter
      measurement, changes in aortic lumen volume and thrombus volume may be more
      appropriate to discriminate successful from failed exclusion.

PMID- 8760981
TI  - Regional differences in mechanical properties between major arteries--an
      experimental study in sheep.
AB  - PURPOSE: To study possible differences in mechanical properties between central
      (abdominal aorta) and more peripheral (common carotid and common femoral)
      arteries validating an earlier non-invasive study in children showing that
      central arteries are more distensible than peripheral ones. As invasive blood
      pressure was needed, but ethically impossible to obtain in children in an
      experimental setting, an animal model was chosen. DESIGN: Open experimental
      study. SETTING: Animal laboratory at university hospital. MATERIAL AND METHODS:
      The pulsatile vessel wall movements of the abdominal aorta (AA), common femoral
      (CFA) and common carotid (CCA) artery of nine sheep were examined using an
      ultrasound phase-locked echo-tracking technique. Intra-arterial blood pressure
      was measured and pressure-diameter relations, pressure strain elastic modulus
      (Ep) and stiffness (beta) calculated. Distensibility was defined as the inverse
      of Ep and stiffness. RESULTS: The AA showed lower values for Ep and stiffness
      (beta) than the CFA (p = 0.002) and CCA (p = 0.006), i.e. the latter two vessels
      were stiffer. The pressure-diameter relations confirmed these differences and
      showed a non-linearity for all three vessels with increased stiffness above 70-90
      mm Hg. CONCLUSION: This study on young animals supports earlier findings of
      differences in mechanical properties between central and more peripheral arteries
      seen in healthy children. As pathologies between these vessels differ, with
      dilatation of the abdominal aorta and occlusive disease in the more peripheral
      vessels, part of the explanation might be found in the mechanical properties of
      the healthy vessels, characterised here with the echo-tracking technique.

PMID- 8760982
TI  - Incisional hernias are more common in aneurysmal arterial disease.
AB  - OBJECTIVE: To test the hypothesis that incisional hernia was a more frequent
      complication following aortic reconstructive surgery in patients with aneurysmal
      as opposed to occlusive aortic disease. DESIGN: A retrospective review. MATERIALS
      AND METHODS: All patients having aortic reconstructive surgery at a teaching
      hospital between 1988 and 1992 were identified and recalled to be examined for
      evidence of an incisional hernia. RESULTS: Of the 134 patients having aortic
      reconstructive surgery, 87 were available to be examined by an independent
      clinician. The overall incisional hernia rate was 28%. Patients with aneurysmal
      disease were significantly more likely to develop an incisional hernia after
      elective surgery than patients with occlusive disease (p = 0.04). None of the
      other variables investigated, including age, chronic obstructive airways disease,
      diabetes, smoking, wound infection, obesity, length of intensive care unit stay
      and number of units of blood transfused, were significantly related to the
      complication of incisional hernia. CONCLUSION: Incisional hernia is a common
      complication of aortic reconstructive surgery, especially in patients with
      aneurysmal disease.

PMID- 8760983
TI  - Percutaneous transluminal angioplasty of the infrarenal aorta: initial outcome
      and long-term clinical and angiographic results.
AB  - OBJECTIVE: Report of 1-8 year follow-up of patients treated by percutaneous
      transluminal angioplasty (PTA) for obstructive atherosclerosis of the infrarenal
      aorta. DESIGN: Cohort study. MATERIALS: Thirty-eight patients aged 26-81 years
      (mean 50 years) were submitted to undergo percutaneous transluminal angioplasty
      of the infrarenal aorta. All patients had symptomatic isolated stenotic lesions
      of the aorta located below the renal arteries and above the bifurcation. Stenoses
      at bifurcation-level and the iliac arteries were excluded. METHODS: PTA of the
      aorta was performed under local anaethesia in the radiological department.
      Clinical symptoms and ankle/brachial indices were registered before, directly
      after the procedure and at follow-up. Angiography was performed in all patients
      pre- and post-procedure, and at follow-up. All patients received angiography in
      March 1995. Clinical data were analysed based on intention-to-treat. RESULTS:
      Initial clinical and angiographic success was achieved in 36 patients (94%). Mean
      follow-up was 34 months (range 1-92). Recurrent stenosis was seen in seven
      patients (19%) at follow-up. Only five (13%) of these had recurrent symptoms and
      were treated successfully with a second PTA. No major complications were seen.
      CONCLUSION: These results show PTA to be a safe, minimally-invasive and effective
      alternative to surgery in case of symptomatic stenosis of the infrarenal
      abdominal aorta.

PMID- 8760984
TI  - Factors associated with early failure of arteriovenous fistulae for haemodialysis
      access.
AB  - The radiocephalic arteriovenous fistula remains the method of choice for
      haemodialysis access. In order to assess their suitability for fistula formation,
      the radial arteries and cephalic veins were examined preoperatively by ultrasound
      colour flow scanner in conjunction with a pulse-generated run-off system.
      Intraoperative blood flow was measured after construction of the fistulae. Post
      operative follow-up was performed at various intervals to monitor the development
      of the fistulae. Radial artery and cephalic vein diameter less than 1.6 mm was
      associated with early fistula failure. The intraoperative fistula blood flow did
      not correlate with the outcome of the operation probably due to vessel spasm from
      manipulation. However, blood flow velocities measured non-invasively 1 day after
      the operation were significantly lower in fistulae that failed early compared
      with those that were adequate for haemodialysis. Most of the increase in fistula
      diameter and blood flow occur within the first 2 weeks of surgery.

PMID- 8760985
TI  - The influence of age on long-term survival pattern of patients operated on for
      lower limb ischaemia.
AB  - OBJECTIVE: To study the long-term survival patterns of patients subjected to
      surgery for lower limb ischaemia. DESIGN: A retrospective clinical study.
      SETTING: University Hospital. MATERIALS: A series of 1411 patients older than 50
      years operated on for all stages of lower limb ischaemia. CHIEF OUTCOME MEASURES:
      Observed and expected long-term survival rates were calculated. Relative
      survival, defined as the ratio of the observed to the expected survival rates,
      was studied for age influence. MAIN RESULTS: The observed 10 year survival rate
      of 26% was significantly lower than the expected of 49%. Although women were 8
      years older than men at the time of the operation they had similar long-term
      survival and relative survival. An inverse proportionality was found between the
      patient's age at the time of the operation and relative survival. The young
      patients experienced a 10 year mortality rate three to four times the expected,
      while the older had a mortality that was elevated 25-50% from the expected.
      CONCLUSIONS: Patients operated on for lower limb ischaemia experience a
      significantly lower long-term survival than that of a demographically matched
      population. This relative survival is significantly influenced by the patient's
      age at the time of the operation.

PMID- 8760986
TI  - Neutrophil elastase, von Willebrand factor, soluble thrombomodulin and
      percutaneous oxygen in peripheral atherosclerosis.
AB  - OBJECTIVES: To test the hypothesis that endothelial cell damage and hypoxia are
      related to the activity of neutrophil elastase in patients with peripheral
      atherosclerosis. DESIGN: A cross-sectional serological study in a tertiary
      referral, University Hospital. MATERIALS: Venous blood was obtained from 22
      patients with peripheral vascular disease and an equal number of age and sex
      matched controls. METHODS: Neutrophil elastase and two markers of endothelial
      cell damage (von Willebrand factor and soluble thrombomodulin) were measured in
      plasma by ELISA. Hypoxia was measured by percutaneous oxygen (by oximeter) at the
      dorsum of the foot. RESULTS: Patients had higher von Willebrand factor, higher
      soluble thrombomodulin and higher elastase but lower percutaneous oxygen (all p <
      0.001). In the patient's group, there were significant inverse correlates between
      von Willebrand factor and percutaneous oxygen (p = 0.004) and between soluble
      thrombomodulin and percutaneous oxygen (p = 0.011) while elastase correlated
      positively with soluble thrombomodulin (p = 0.023). CONCLUSIONS: Our data support
      the hypothesis that release of elastase from activated neutrophils relates to
      endothelial cell damage. This may contribute to hypoxia and may result in the
      deterioration in clinically assessed atherosclerosis.

PMID- 8760987
TI  - Angioscopically-assisted in situ saphenous vein bypass for infrainguinal
      revascularisation.
AB  - OBJECTIVES AND STUDY DESIGN: The diagnostic capability of angioscopy for
      endoluminal evaluation is established and its superiority over arteriography for
      completion studies has been confirmed. The therapeutic use of angioscopy in vein
      graft preparation is more controversial. The aim of this prospective study was to
      establish whether angioscopic vein preparation confers real benefits over
      existing techniques. METHODS: Forty-seven patients were randomised to either full
      angioscopic (ANG) vein preparation (23 patients) or conventional (CON) in situ
      grafting (19 patients). All patients underwent completion studies with
      arteriography and angioscopy and postoperatively, entered a Duplex graft
      surveillance programme. RESULTS: There was a significant difference in the
      incidence of wound morbidity: 26% in the ANG group as against 63% in the CON
      group (Fisher's exact test: p = 0.043), but no significant differences with
      respect to duration of operation, duration of vein graft preparation, length of
      hospital stay and both 30 day and 12 month secondary cumulative patencies (log
      rank test: p > 0.5). Completion angioscopy detected eight persistent valve cusps
      in six patients, all missed at arteriography, but failed to detect arteriovenous
      fistulae. CONCLUSIONS: Angioscopic preparation reduces wound morbidity and
      complements arteriography for detecting intraoperative defects. A large,
      prospective, randomised trial is now warranted to fully evaluate the potential
      therapeutic role of angioscopy with respect to current vascular practice.

PMID- 8760988
TI  - Interobserver variability in measuring the dimensions of the abdominal aorta:
      comparison of ultrasound and computed tomography.
AB  - OBJECTIVES: To examine the interobserver variability in measuring the abdominal
      aorta by ultrasound (US) and computed tomography (CT). DESIGN: A prospective
      clinical study in a university hospital. MATERIALS: Thirty-three patients whose
      abdominal aortas were scanned both with CT and US as a part of aneurysm
      investigation or for a variety of other reasons. METHODS: Three radiologists
      measured abdominal aortic diameters by US and CT. The interobserver differences
      (IOD) in US and CT and intraobserver differences for CT-US-pairs were analysed by
      various statistical methods. A new concept of "clinically acceptable difference"
      (CAD) was adopted denoting differences of less than 5mm. RESULTS: The IOD in US
      was 2mm or less in 65% of the anteroposterior and 61% of the transverse
      measurements and 5mm or more in 11% of the anteroposterior and 14% in the
      transverse measurements in 102 observer pairs for all aortas. The IODs were
      significantly larger in measuring the aneurysmal aortas compared with normal
      aortas (p < 0.001). The CAD-value for the aneurysmal aortas was 84% in the
      anteroposterior and 82% in the transverse directions. In CT the IODs were 2mm or
      less in 62% of the anteroposterior and 66% of the transverse measurements and 5mm
      or more in 12% of both anteroposterior and transverse measurements in 94 observer
      pairs for all aortas. The CAD-value in the aneurysmal aortas was 91% in the
      anteroposterior and 85% in the transverse directions. There was no significant
      difference between the US and CT CAD-levels. The absolute CT-US difference of an
      individual observer was 2mm or less in 54%, 5mm or more in 17% and 10mm or more
      in 2% of the anteroposterior measurements in the 95 CT-US pairs. In the
      transverse direction the corresponding figures were: 2mm or less in 63%, 5mm or
      more 13% and 10mm or more in 2% of the pairs. The diameters obtained by US were
      smaller in 84% of the cases compared with those of CT in measuring the maximum
      aortic diameter in anteroposterior direction, whereas the same figure for the
      transverse measurements was 59%. CONCLUSIONS: Both US and CT measurements are
      subject to significant interobserver variability that must be taken into account
      in the clinical follow-up of small abdominal aortic aneurysms and in screening
      studies. Neither of these methods can be considered as a 'gold standard'.

PMID- 8760989
TI  - The effect of adjacent segment disease on the accuracy of colour duplex scanning
      for the diagnosis of lower limb arterial disease.
AB  - OBJECTIVE: To assess the effect of multisegment disease upon the accuracy of
      lower limb colour Duplex scanning. DESIGN: Prospective, semi-blind study.
      SETTING: Vascular Laboratory and Radiology Department, University Hospital.
      METHODS: A total of 148 limbs (1106 individual arterial segments) were examined
      from the distal aorta to the origins of the tibial arteries by colour-coded
      Duplex and arteriography. Individual segments were graded as 0-49%, 50-99%
      diameter reduced or occluded on the basis of peak systolic velocity ratios < 2.0,
      > or = 2.0 or an absent Doppler signal, and compared with similarly graded
      segments from blinded angiographic studies. The agreement (Kappa analysis)
      between Duplex and arteriography in segments adjacent to at least one proximal or
      distal > or = 50% diameter reducing lesion was then compared to the agreement
      between segments free of adjacent disease. RESULTS: For isolated areas of
      disease, the kappa value (95% confidence interval) of agreement between Duplex
      ultrasonography and arteriography was 0.63 (0.53-0.73) and in the presence of
      neighbouring disease the value was 0.78 (0.73-0.83). CONCLUSION: We conclude
      therefore that providing appropriate criteria are used, Duplex assessment of
      lower limb arterial disease is not adversely affected by adjacent disease.

PMID- 8760990
TI  - Iatrogenic AV-fistula treated by a graft-covered self-expandable stent.

PMID- 8760991
TI  - Intentional extraluminal recanalisation of the femoropopliteal segment following
      perforation during percutaneous transluminal angioplasty.

PMID- 8760992
TI  - Mycotic aneurysm of the carotid artery due to Salmonella enteritidis associated
      with multiple brain abscesses.

PMID- 8760993
TI  - Cranial nerve injury.

PMID- 8760994
TI  - Female perversion: scenes and strategies in analysis and culture.
AB  - The author presents some ideas derived from observation in analysis about
      differing positions of Freud and Jung on perversion and about probable
      differences in perverse structural elements of women in contrast to men. In
      general perversion is understood as a defence of the self; in particular with
      women it is seen as a defensive way of achieving a false wholeness, a pseudo
      androgyny. A case study describes the unfolding of a perverted transference. The
      importance of reaching the analyst and being understood by the analyst through
      projective identification is stressed. Quite often a sexually abusing mother
      seems to play an important role in generating female perversion; the implications
      in analysis are discussed as well as some ideas about culture and gender.

PMID- 8760995
TI  - The animating body: psychoid substance as a mutual experience of psychosomatic
      disorder.
AB  - Starting from Jung's hypothesis of 'the psychoid', the author suggests that the
      concept can be extended and understood as a dynamic, relational and interpersonal
      experience-especially in regressed analytic relations. The author then defines
      his use of the term 'animating body' as having to do with primitive animal
      imagery and with psychosomatic symptoms stemming from disturbed pre-verbal and
      pre-whole-object stages of development. A case of a borderline patient is
      presented, whose projective identifications into the analyst infected him with
      her psychosomatic disorder, with her internalized Oedipal confusion and
      necessarily induced a mutually similar animal dream symbolism. If these embodied
      countertransference experiences (of desperate merging and sickening
      identification) can be lived through (tolerated and survived), thought through
      and interpreted, then they can actually become enlivening and lead to a
      therapeutic psychosomatic co-ordination.

PMID- 8760996
TI  - Alchemy, homeopathy and the treatment of borderline cases.
AB  - Homeopathy is presented as a modality of potential usefulness in the treatment of
      borderline patients refractory to psychoanalytic work. In these instances a
      minimally adequate centre of consciousness did not solidify from the identity
      with the psychoid stratum. In the view of Alchemy, this failure of the mind to
      separate from the unio naturalis or massa confusa could be remedied by a
      medicamentum spagyricum, an archtypal essence acting according to the simile
      principle, which was to be extracted from various substances. Homeopathy is
      described as a modern, clinically effective modification of the alchemistic
      method. Two cases example are given for illustration.

PMID- 8760997
TI  - 'Reductive' analysis in the light of modern infant research.
AB  - From a Jungian viewpoint the findings of modern infant research can be seen as
      dealing in minute detail with the process by which the Self, the archetype of
      order, becomes incarnated in the infant and organizes the individual's
      development and maturation in accordance with the facilitating environment.
      Viewing Lichtenberg's 'groundplan of the infant-environment system' as
      archetypal, the paper traces the impact of this groundplan on the interactive
      field in analysis. Descriptions are offered of key issues in infant research,
      such as the growing sense of self (emerging self, core self, subjective and
      verbal self) with its various interpersonal needs and experiences (Stern 1985),
      the motivational systems (Lichtenberg 1989), the precursors of fantasy life i.e.
      the 'RIGs' (representations of interactions that have been generalized') (Stern
      1985), and the categorical and vitality affects. The paper's main concern,
      however, is the practical application of these findings to the analytic
      situation, in so far as they cultivate a deeper sensitivity to and understanding
      of the emotional nuances, the 'metacommunications', so to speak, beneath the
      discourse of manifest issues and 'contents' of the unconscious.

PMID- 8760998
TI  - Mary Williams (3 July 1905-4 January 1996).

PMID- 8760999
TI  - Response of a protein disulfide isomerase-like activity of transitional
      endoplasmic reticulum to all-trans retinol.
AB  - Isolated membrane fractions enriched in vesicles of transitional endoplasmic
      reticulum from rat liver exhibited protein disulfide isomerase-like activity of
      low specific activity. Activity was measured as the ability to restore activity
      to reduced, denatured and oxidized (scrambled) RNase. Submicromolar
      concentrations of retinol either stimulated or inhibited this activity depending
      on the composition of the redox buffer. In the presence of 1 microM reduced
      glutathione, micromolar concentrations of retinol stimulated the activity while
      higher or lower concentrations were less effective. With scrambled RNase, retinol
      was largely without effect in the absence of reduced glutathione or in the
      presence of oxidized glutathione. In the presence of NADH, retinol inhibited the
      protein disulfide-like activity over the same range of concentrations where
      retinol stimulated in the presence of reduced glutathione. These responses were
      observed with scrambled and inactive RNase and with reduced and inactive RNase as
      substrates. Also inhibited by retinol in these membrane preparations was their
      ability to oxidize NADH. Thus the retinol-modulated protein disulfide isomerase
      activity appears to correlate with the presence in transitional endoplasmic
      reticulum of an activity capable of oxidizing NADH in the presence of potassium
      cyanide that also was inhibited by submicromolar concentrations of retinol.

PMID- 8761000
TI  - Effects of metronidazole and its metabolites on histamine immunosuppression
      activity.
AB  - We have previously reported that metronidazole treatment increases human
      lymphocyte proliferation showing individual differences. This drug and its
      metabolites are imidazole compounds like histamine and cimetidine. The first is
      an endogenous amine that inhibits T-helper lymphocyte proliferation, and the
      second is a histamine antagonist. We presently report the in vitro effects of
      histamine, cimetidine, imidazole, metronidazole and its two principal metabolites
      (the acetic acid and hydroxy forms), on the mitogenic response to
      phytohemagglutinin (PHA) stimulation of human peripheral blood lymphocytes.
      Histamine decreased lymphocyte proliferation while (in order of potency)
      cimetidine, the hydroxy metabolite of metronidazole, imidazole and metronidazole,
      increased the mitogenic response to PHA in a dose-response fashion. The acetic
      acid metabolite lacked immunomodulatory effects. Competitive studies showed that
      cimetidine, metronidazole, and the hydroxy metabolite blocked the inhibitory
      effect of histamine on lymphocyte proliferation in a dose-related manner. This
      blockage was non-competitive, suggesting that the target of the imidazole
      compounds was not the active site of the H2 receptor.

PMID- 8761001
TI  - (-)-Stepholidine acts as a D1 partial agonist on firing activity of substantia
      nigra pars reticulata neurons in 6-hydroxydopamine-lesioned rats.
AB  - (-)-Stepholidine (SPD), a novel dopamine (DA) D1 and/or D2 receptor antagonist in
      normosensitive animals, shows agonistic effects on D1 receptors in rotational
      behavior of 6-hydroxydopamine (6-OHDA)-lesioned rats. To further characterize the
      pharmacological properties of SPD, we investigated the effects of SPD on firing
      activity of substantia nigra pars reticulata (SNR) neurons in different sensitive
      models. In control rats, the selective D1 agonist SKF38393 (4 mg/kg, i.v.)
      induced inconsistent changes (i.e. increase, decrease or no change) in firing of
      SNR neurons. These effects were completely antagonized by SPD (i.v.), regardless
      of the changes induced by SKF38393. SPD (4 mg/kg), per se, increased firing by
      30.9 +/- 14.4%. In reserpinized rats, SKF38393 also induced SPD-reversible
      inconsistent changes as in control rats. Nevertheless, SPD per se produced no
      alteration in firing of SNR neurons. In 6-OHDA-lesioned rats, 5/6 SNR neurons
      were inhibited by SKF38393. The inhibition was completely abolished by Sch23390,
      a selective D1 antagonist (0.5-2 mg/kg), but partially reversed by SPD (1-16
      mg/kg). Moreover, SPD (4 mg/kg) itself caused SNR increased or decreased neuron
      firing, and these effects were completely reversed by Sch23390 (0.5-2 mg/kg) in
      8/12 neurons recorded. These results suggest that SPD acts as a partial agonist
      to D1 receptors in 6-OHDA-lesioned rats, but as an antagonist to D1 receptors in
      normal and reserpinized rats.

PMID- 8761002
TI  - PACAP stimulates c-fos mRNAs in small cell lung cancer cells.
AB  - The effects of PACAP on c-fos mRNA using small cell lung cancer (SCLC) cell was
      investigated. PACAP-27 (100 nM) increased c-fos mRNA 5-fold using NCI-N417 cells.
      The increase was concentration dependent with 0.1 nM PACAP-27 half maximally
      increasing c-fos mRNA. Also the increase in c-fos mRNA caused by PACAP was time
      dependent; being maximal after 1 hour and returning to basal values after 4
      hours. PACAP-38 but not PACAP(28-38) increased c-fos mRNA. One uM PACAP(6-38), a
      PACAP receptor antagonist, inhibited the increase in c-fos mRNA caused by 1 nM
      PACAP. These data indicate that PACAP stimulates nuclear oncogene expression in
      SCLC cells.

PMID- 8761003
TI  - The effect of human recombinant erythropoietin on the growth of a human
      neuroblastoma cell line.
AB  - Erythropoietin is a growth factor. Cancer can be described as disturbance of the
      fine balance of positive and negative growth control mechanisms. The effect of
      human recombinant erythropoietin (EPO) was studied on the cell growth and
      differentiation of a human neuroblastoma cell line (h-NMB). Cell growth curves,
      trypan blue staining and thymidine uptake were used to assess cell proliferation
      and death. To assess cell differentiation, neutral endopeptidase (cell membrane
      enzyme marker), creatine kinase (cytosolic enzyme marker), dopamine uptake
      (dopamine transporter marker) and cell morphology were determined. Specific EPO
      receptor mRNA, by RT-PCR technique, was demonstrated. The incubation of
      erythropoietin with the tumor cell line resulted in inhibition of cell
      proliferation as evidenced in a diminished cell growth. EPO was shown to have
      induced a differentiation process as seen from the two different enzymatic
      markers, membranal and cytosolic, and from the cells dopamine uptake studies.
      However, the morphological changes did not document a full differentiation
      effect. EPO specific antibodies blocked the effects of EPO on cell proliferation
      and creatine kinase activity. In this study, EPO did not produce any sign of
      proliferation in the nervous tumor cell line used.

PMID- 8761004
TI  - Physiological significance of plasma sulfoconjugated dopamine in patients with
      hypertension--clinical and experimental studies.
AB  - Sulfoconjugated catecholamines, especially dopamine sulfate, have recently
      attracted much attention because of the possibility of their conversion to active
      free dopamine by tissue arylsulfatase. In the present study, we have measured the
      plasma levels of free and sulfoconjugated dopamine in patients with hypertension
      and have investigated the physiological significance of sulfoconjugation. Results
      showed that the plasma level of dopamine sulfate in patients with essential
      hypertension was higher than the level in control subjects, and was highest in
      patients with renal hypertension. However, the plasma level of free dopamine
      showed no significant difference between patients with hypertension and normal
      subjects. Moreover, after normalization of blood pressure in hypertensive
      patients with medication, the plasma levels of conjugated dopamine decreased to
      almost the control value. In the experimental study, dopamine sulfate inhibited
      angiotensin II-induced aldosterone release from bovine adrenal cortical cells to
      a similar extent as produced by free dopamine. From these results, we have
      concluded that plasma sulfoconjugated dopamine may regulate free dopamine in the
      plasma of patients with hypertension, and it may have some physiological effects
      on blood pressure regulation.

PMID- 8761005
TI  - Differential effects of chylomicron remnants derived from corn oil or palm oil on
      bile acid synthesis and very low density lipoprotein secretion in cultured rat
      hepatocytes.
AB  - The effects of chylomicron remnants derived from corn oil (rich in n-6
      polyunsaturated fatty acids) and palm oil (rich in long chain saturated fatty
      acids) on bile acid synthesis and very low density lipoprotein secretion in
      cultured rat hepatocytes were studied. Incubation of the cells with corn oil
      remnants led to increased bile acid production, while the secretion of lipid in
      very low density lipoprotein remained unchanged. In contrast, addition of palm
      oil remnants to the medium did not affect bile acid synthesis, but resulted in
      the secretion of cholesterol-rich very low density lipoprotein. These findings
      show that chylomicron remnants of different fatty acid composition have
      differential effects on cholesterol metabolism in liver cells, and provide part
      of the explanation for the hyper- and hypocholesterolaemic effects of saturated
      and polyunsaturated fatty acids.

PMID- 8761006
TI  - Immobilization stress induces c-fos and c-jun immediate early genes expression in
      the heart.
AB  - Emotional stress is considered to be one of the etiological factors in ischemic
      heart disease (IHD) and sudden cardiac death (SCD), mechanisms of which are
      poorly understood. Immediate early genes (IEGs), such as c-fos and c-jun are used
      as tools for detection of cellular activation. Male Wistar rats were exposed to
      acute immobilization (IMO). IMO stress for 30 min induced c-fos and c-jun mRNAs
      expression in the myocardium and the smooth muscle layer of the coronary
      arteries. IMO stress for 2 h also induced Fos and Jun like-immunoreactivities in
      the same regions. Distribution of IEG mRNAs and their protein products in the
      myocardium was not uniform but rather localized. These data provided histological
      evidence for an early cellular event in the stress response whose consequences
      could result in activation of tissues in the myocardium and coronary arterial
      smooth muscle cells which play a role in the pathophysiological changes in IHD
      and SCD.

PMID- 8761007
TI  - Opposite influence of carbohydrates and fat on hypothalamic neurotensin in Long
      Evans rats.
AB  - Neurotensin inhibits food intake when injected in the central nervous system and
      is released after fat ingestion. The aim of the present study was to measure it
      in different brain areas and to determine if it is involved in the long-term
      variations in food intake induced by the ingestion of a high-fat (HF) diet. We
      compared the results with those obtained with 2 low-fat [high-carbohydrates (HC)]
      diets and a well-balanced diet. For this purpose, weanling male Long-Evans rats
      were fed ad libitum for 14 weeks either on a control diet, a HF diet or a HC
      diet. The rats with the HC (high-starch) diet were divided into 2 subgroups: the
      first (HC) drank water and the second (HCS) drank a 25% sucrose solution. During
      the last week of the experiment, energy intake of the HCS rats was significantly
      greater than that of the 3 other groups of rats (+17.2%; p < 0.01; +27.1%; p <
      0.001 and +34.6%; P < 0.001 vs the control, HC and HF rats respectively). NT did
      not vary in the midbrain and particularly in the ventral tegmental area. Its
      concentrations were significantly higher in the 2 HC groups than in the HF rats
      both in the paraventricular (PVN; p < 0.02) and dorsomedial nuclei (DMN; p <
      0.03). In the DMN, they were positively correlated with energy intake (r = 0.39;
      p = 0.027). These results indicate that hypothalamic neurotensin is indeed
      involved in the long-term modulation of feeding behavior by diet composition and
      that fat is the more potent macronutrient for its regulation.

PMID- 8761008
TI  - Inhibition by multivalent cations of contraction induced by Chinese cobra venom
      cardiotoxin in guinea pig papillary muscle.
AB  - The effects of cardiotoxin (CTX), purified from the venom of Chinese Cobra (Naja
      naja atra) by a three-step chromatography, on the contractile responses of
      isolated guinea pig papillary muscle preparation and its antagonism by lanthanum
      ion (La3+) and divalent cations were examined. CTX induced tonic contraction
      following a transient augmentation of electrically evoked rhythmic contractions,
      which is similar to that seen in perfused heart preparation. Multivalent cations,
      La3+, Ca2+, Mn2+ and Mg2+, concentration-dependently blocked CTX-induced
      contraction. In Ca(2+)-free medium, CTX did not induce contraction and CTX
      induced contraction was not modified in Na(+)-free medium. Nifedipine (1
      mumol/L), effectively blocked KCl-induced contracture, but only partially
      inhibited CTX-induced contraction; thus suggesting that Ca2+ influx induced by
      CTX utilizes channels other than L-type Ca2+ channels. These cations may compete
      with CTX for the negatively charged membrane binding site which is responsible
      for the modulation of Ca2+ movement.

PMID- 8761009
TI  - Effect of glycosylation on cloned ANF-sensitive guanylyl cyclase.
AB  - Cloned ANF-sensitive guanylyl cyclase (GC-A) and ANF-sensitive guanylyl cyclase
      from adrenal cortex differ in their sensitivity to the ANF analogs atriopeptin 1
      and urodilatin. To test the hypothesis that these differences are due to
      different glycosylation, we investigated the effect of the N-glycosylation
      inhibitor tunicamycin on GC-A. Tunicamycin altered the response of GC-A to
      atriopeptin 1 and urodilatin, whereas the sensitivity to ANF remained unchanged.
      These data indicate that agonist specificities of different ANF-sensitive
      guanylyl cyclases are influenced by carbohydrate moieties.

PMID- 8761010
TI  - Use of antisense oligodeoxynucleotide to determine delta-opioid receptor
      involvement in [D-Ala2]deltorphin II-induced locomotor hyperactivity.
AB  - Intracerebroventricularly (i.c.v.)-administered [D-Ala2]deltorphin II (20
      micrograms) produced a marked locomotor hyperactivity in male ICR mice. The
      locomotor hyperactivity induced in response to i.c.v. [D-Ala2]deltorphin II (20
      micrograms) was suppressed by pretreatment with naltriben (NTB, 10 micrograms)
      but not 7-benzylidene naltrexone (BNTX, 1 microgram) and D-Phe-Cys-Tyr-D-Try-Orn
      Thr-Phe-Thr-NH2 (CTOP, 100 ng). The influence of antisense oligodeoxynucleotide
      to delta-opioid receptor mRNA (delta-AS oligo) or a mismatch oligodeoxynucleotide
      (MM oligo) on the locomotor hyperactivity induced by [D-Ala2]deltorphin II was
      determined. Groups of mice pretreated i.c.v. with delta-AS oligo (1 microgram),
      MM oligo (1 microgram) or saline (4 microliters) once a day for 3 days, were
      injected i.c.v. [D-Ala2]deltorphin II (10 or 20 micrograms) and the locomotor
      response to [D-Ala2]deltorphin II was measured. The locomotor hyperactivity of
      i.c.v. [D-Ala2]deltorphin II (10 or 20 micrograms) were significantly suppressed
      by i.c.v. pretreatment with delta-AS oligo but not MM oligo. The present results
      indicate that pretreatment with delta-AS oligo suppresses mouse locomotor
      hyperactivity produced by stimulation of delta 2-opioid receptors in the brain.

PMID- 8761011
TI  - Endocrine, paracrine and autocrine actions of prolactin on immune cells.
AB  - The immune response is regulated by locally released factors, collectively
      referred to as cytokines. Data on the human immune system have convincingly
      demonstrated that the hormone prolactin (PRL), in addition to exerting its
      endocrine control on the immune system, acts as a cytokine in that it is released
      within the immune system and regulates the lymphocyte response by paracrine and
      autocrine mechanisms. Both lymphocyte and pituitary PRLs are under the control of
      immune factors. Synthesis of human PRL by lymphocytes is induced by T-cell
      stimuli, while increased release of PRL by the pituitary, observed in vivo after
      immune challenge, may be mediated by cytokines produced by monocyte-macrophages.
      Since hyperprolactinemia and hypoprolactinemia are both immunosuppressive,
      physiological levels of circulating PRL must be necessary to maintain basal
      immunocompetence. The effects of Cyclosporin (CsA) on IL-2 and PRL gene
      activation and the analysis of the intracellular signaling events downstream IL-2
      and PRL receptors suggest coordinate actions of these two cytokines during T cell
      activation.

PMID- 8761012
TI  - Cocaethylene is as cardiotoxic as cocaine but is less toxic than cocaine plus
      ethanol.
AB  - Cocaethylene is a pharmacologically active cocaine metabolite that is produced in
      the liver by the transesterification of cocaine only in the presence of ethanol.
      The acute cardiovascular effects of cocaethylene are not known. We compared the
      acute cardiovascular effects of cocaethylene with cocaine and with cocaine plus
      ethanol in 18 dogs. We administered cocaethylene 7.5 mg/kg to 6 dogs, cocaine 7.5
      mg/kg to 6 dogs, and cocaine 7.5 mg/kg plus ethanol 1 gm/kg to 6 dogs. The dose
      of each drug was chosen to produce in dogs the concentrations of cocaethylene or
      cocaine that have been measured in patients who have experienced cardiotoxic
      reactions to cocaine or cocaine plus ethanol. Arterial, left ventricular (LV),
      pulmonary artery wedge pressures (PAWP), the maximum rate of LV pressure rise
      [(dP/dt)max] and fall [(dP/dt)min], and heart rate (HR) were continuously
      measured. Stroke volume was determined 3 times during the first hour after drug
      administration then hourly for four hours. The concentrations of cocaethylene and
      cocaine peaked in the serum at 3717 +/- 651 ng/ml and 4140 +/- 459 ng/ml,
      respectively, two minutes after each bolus. The median half-life of cocaethylene
      was 144.3 minutes whereas the median half-life of cocaine was 96.7 minutes (p <
      0.01). Cocaethylene maximally decreased (dP/dt)max by 44%, (dP/dt)min by 29%, and
      stroke volume by 28% (all p < 0.01) and increased the PAWP by 50% (p < 0.02) and
      the HR by 13% (p = NS) during the first hour. Cocaine maximally decreased
      (dP/dt)max by 40%, (dP/dt)min by 31%, and the stroke volume by 26% and increased
      the PAWP by 100% and the HR by 46% (all p < 0.01) during the first hour. Ethanol
      plus cocaine maximally decreased (dP/dt)max by 68%, (dP/dt)min by 78% and the
      stroke volume by 49% and increased the PAWP by 118% and the HR by 74% (all p <
      0.01) during the first hour. In this last group, (dP/dt)max and stroke volume
      remained depressed by approximately 20% (p < 0.01) for five hours. We conclude
      that cocaethylene is as toxic as cocaine to the myocardium but is less toxic than
      ethanol plus cocaine.

PMID- 8761013
TI  - Angiotensin converting enzyme gene polymorphism and renal artery resistance in
      patients with insulin dependent diabetes mellitus.
AB  - The present study was carried out to elucidate whether renal hemodynamic changes
      are associated with angiotensin converting enzyme (ACE) gene polymorphism in
      patients with insulin dependent diabetes mellitus (IDDM). We studied 32 Japanese
      patients with IDDM (aged 15 +/- 3 years in mean +/- SD) without renal failure or
      retinopathy. Renal hemodynamics were examined by duplex Doppler sonography and
      arterial resistance index was calculated. ACE genotypes were determined by
      polymerase chain reaction amplification. Resistance index (RI) of arcuate
      arteries in IDDM patients with DD genotype was significantly elevated, being 0.64
      +/- 0.04, 0.66 +/- 0.05, and 0.71 +/- 0.05 for II, ID and DD genotype groups,
      respectively (II vs. DD, p < 0.02). In patients with DD genotype with
      normoalbuminuria (n = 27), it was also significantly elevated in DD genotype
      patients (II vs. DD, p < 0.02). In addition, multiple regression analysis with a
      forward elimination procedure showed that only the ACE genotype was associated
      with RI of arcuate arteries (R2 = 0.24, p < 0.01) among the parameters of sex,
      age, IDDM duration, body mass index, HbA1c, plasma glucose levels, serum levels
      of total cholesterol and creatinine, urinary albumin excretion index, mean blood
      pressure and ACE genotype. The present study demonstrated that renal arterial
      resistance is elevated in IDDM patients with DD genotype. ACE gene polymorphism
      which could be linked to intrarenal circulatory disturbance may be associated
      with the initiation and progression of diabetic nephropathy.

PMID- 8761014
TI  - Lymphocyte norepinephrine and epinephrine, but not plasma catecholamines predict
      lymphocyte cAMP production.
AB  - Endogenous norepinephrine (NE) and epinephrine (E) were demonstrated in
      lymphocytes isolated from peripheral venous blood. In 13 young subjects
      lymphocyte NE and E averaged 14.3 and 1.9 pg per 10(7) cells, respectively. The
      ratio NE/E was similar in plasma and in lymphocytes. Highly significant
      correlations were obtained between lymphocyte NE and E on the one hand and cAMP
      in lymphocytes on the other both in the basal state and after stimulation with
      isoproterenol. In a group of elderly subjects lymphocyte NE concentration was
      significantly reduced in long-term smokers as compared to non-smokers (7 and 35
      pg/10(7) cells, respectively), whereas plasma NE was increased in smokers.
      Addition of exogenous NE or propranolol to blood samples did not change
      lymphocyte NE concentration in in vitro experiments. Variability in endogenous
      lymphocyte concentration of E in 9 young subjects, correlated with concomitant
      changes in number of NK(CD3-CD56+) cells and cAMP. It is concluded that
      endogenous lymphocyte NE and E concentrations in healthy subjects reflected basal
      cAMP production in lymphocytes and lymphocyte subset composition.

PMID- 8761015
TI  - Endotoxin depletes ascorbate in the guinea pig heart. Protective effects of
      vitamins C and E against oxidative stress.
AB  - The effect of acute endotoxin-induced septic shock on myocardium oxidative stress
      after low or high vitamin C and/or E dietary supplementation was studied in
      guinea pigs, laboratory animals which, like human, do not have capacity for
      ascorbate synthesis. Neither the antioxidant enzymes or GSH were modified by
      endotoxin and vitamin treatments. Vitamin E showed a strong capacity to protect
      the myocardium against both enzymatic and non-enzymatic lipid peroxidation even
      in the presence of endotoxin. Vitamin C supplementation increased heart ascorbate
      whereas endotoxic shock totally depleted the heart ascorbate of vitamin C
      supplemented animals without changing vitamin E. Endotoxin significantly
      increased myocardium uric acid, a marker of ischemia induced oxidative stress, in
      animals fed with low vitamin C levels. This increase was totally prevented in
      vitamin C supplemented, but not in vitamin E supplemented animals. Strongly
      depressed levels of plasma vitamin C have been recently described in sepsis in
      human patients. The results suggest that ascorbate is a primary antioxidant
      target in the heart of endotoxin treated mammals lacking the capacity to
      synthesize ascorbate and that ascorbate can have a protective value against
      endotoxin-induced free radical damage in the myocardium. Implications of these
      results for the possible preventive role of vitamin C in humans during sepsis are
      discussed.

PMID- 8761016
TI  - Cannabinoid receptor stimulation of guanosine-5'-O-(3-[35S]thio)triphosphate
      binding in rat brain membranes.
AB  - Cannabinoid receptors belong to the class of G-protein-coupled receptors which
      inhibit adenylyl cyclase. Coupling of receptors to G-proteins can be assessed by
      the ability of agonists to stimulate guanosine-5'-O-(3-[35S]thio)triphosphate
      ([35S]GTP gamma S) binding in the presence of excess GDP. The present study
      examined the effect of cannabinoid agonists on [35S]GTP gamma S binding in rat
      brain membranes. Assays were conducted with 0.05 nM [35S]GTP gamma S, incubated
      with rat cerebellar membranes, 1-30 microM GDP and the cannabinoid agonist WIN
      55212-2. Results showed that the ability of WIN 55212-2 to stimulate [35S]GTP
      gamma S binding increased with increasing concentrations of GDP, with 10-30
      microM GDP providing approximately 150-200% stimulation by the cannabinoid
      agonist. The pharmacology of cannabinoid agonist stimulation of [35S]GTP gamma S
      binding paralleled that of previously reported receptor binding and adenylyl
      cyclase assays, and agonist stimulation of [35S]GTP gamma S binding was blocked
      by the cannabinoid antagonist SR141716A. Brain regional studies revealed
      widespread stimulation of [35S]GTP gamma S binding by WIN 55212-2 in a number of
      brain areas, consistent with in vitro [35S]GTP gamma S autoradiography. These
      results demonstrate that [35S]GTP gamma S binding in the presence of excess GDP
      is an effective measure of cannabinoid receptor coupling to G-proteins in brain
      membranes.

PMID- 8761017
TI  - 18F-desmethoxyfallypride: a fluorine-18 labeled radiotracer with properties
      similar to carbon-11 raclopride for PET imaging studies of dopamine D2 receptors.
AB  - We have developed (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-18F-fluoropropyl)-2
      methoxybenzamide (18F-desmethoxyfallypride) as a fluorine-18 radiotracer with
      properties analogous to that of 11C-raclopride. In vitro experiments in rat brain
      homogenates showed an association rate constant of 2.16 x 10(8) M(-1)min(-1) and
      a dissociation rate constant of 0.073 min(-1). High striatal uptake (up to 0.08%
      injected dose/cc) of 18F-desmethoxyfallypride in rhesus monkeys was observed in
      PET experiments. The radiotracer cleared from the striata with a dissociation
      rate of 1.80 x 10(-2) min(-1). Striatum to cerebellum ratios peaked at 3.0 in 30
      min after which they decreased steadily. Intravenously administered haloperidol
      displaced specifically bound 18F-desmethoxyfallypride with a koff of 0.058 min(
      1). Synaptic dopamine released by the treatment of the monkeys with d-amphetamine
      increased the dissociation rate of 18F-desmethoxyfallypride to 0.83 min(-1) thus
      reducing specifically bound 18F-desmethoxyfallypride by 56% over a period of 42
      mins compared to a reduction of only 20% in controls during this time period. The
      sensitivity of 18F-desmethoxyfallypride towards competition with dopamine should
      make this radiotracer useful in PET studies to evaluate in vivo pharmacological
      effects of various agents that alter levels of endogenous dopamine.

PMID- 8761018
TI  - Advanced glycation endproducts-associated parameters in the peripheral blood of
      patients with Alzheimer's disease.
AB  - Advanced glycation endproducts (AGEs), structural components of beta-amyloid
      plaques and neurofibrillary tangels, have been implicated in the pathogenesis of
      Alzheimer's disease. AGE levels, measured by fluorescence, and their precursor
      molecules such as glucose and its Amadori product, fructosylamine, were measured
      to examine the question whether the reported increased level of AGEs in the brain
      is reflected in an increase in AGE-associated parameters in peripheral blood.
      Lactoferrin, proposed to play an important role in the interaction of AGEs with
      their receptors, was determined by ELISA. All AGE-associated parameters showed
      trends to lower values in patients with Alzheimer's disease compared with non
      demented controls. Albumin and total iron were not significantly different
      between the groups. In contrast to diabetes and renal failure, where high levels
      of AGEs and their precursors are present in tissue as well as in peripheral
      blood, elevated CNS AGE levels in patients with Alzheimer's disease are
      manifested without detectable peripheral changes.

PMID- 8761019
TI  - Melatonin increases the in situ activity of tyrosine hydroxylase in the
      mediobasal hypothalamus of male Syrian hamsters.
AB  - The effects of daily late afternoon injections of melatonin on the in situ
      activity of tyrosine hydroxylase (TH) were examined in the median
      eminence/arcuate region of the mediobasal hypothalamus (MBH) and the
      neurointermediate lobe (NIL) of the male Syrian hamster. TH activity was
      determined in tissue extracts by measuring the accumulation of L-DOPA following
      administration of the dopa decarboxylase inhibitor, NSD-1015. After 9 weeks of
      melatonin treatment, highly significant increases in the activity of MBH TH were
      demonstrated over a 24 hr period, compared to saline-treated controls. Melatonin
      induced elevations in TH occurred concomitantly with decreases in
      tuberoinfundibular dopamine (TIDA) and tuberohypophyseal dopamine (THDA)
      concentrations. Similar findings were observed in castrated hamsters, indicating
      that the melatonin-induced increase in TH was not secondary to melatonin-induced
      changes in circulating levels of gonadal hormones. These data led to the
      interpretation that melatonin treatment elevated TIDA synthesis either through a
      direct action on the arcuate nuclei or on neurons impinging on these nuclei.

PMID- 8761020
TI  - V2-receptor blockade enhances pressor response to vasopressin: gender difference.
AB  - The present study was performed to determine if the attenuated pressor response
      to vasopressin in conscious non-estrous female rats is due in part to an enhanced
      V2-like receptor vasodilator action. In male rats, infusion of vasopressin at a
      rate of 1 ng.min(-1).kg body weight-1 (wt) resulted in an increase in mean
      arterial blood pressure (MABP) of about 20 mm Hg. Thirty minutes after beginning
      the infusion of vasopressin, the iv bolus injection of a non-peptide V2-receptor
      antagonist, OPC-31260 (2 mg.kg body wt-1), resulted in a further gradual increase
      in MABP of approximately 8 mm Hg in the next 60 min (p < 0.05). Thus, the pressor
      response to vasopressin was greater in OPC-31260-treated than in vehicle-treated
      male rats (p < 0.01). The pressor response to vasopressin 30 min after the start
      of its infusion was lower (about 8 mm Hg) in non-estrous female rats than in
      males. During the next 60 min of vasopressin infusion, there was a small further
      increase (p < 0.05) in MABP in the females given either OPC-31260 or its saline
      vehicle. In contrast to the male rats, however, there was no difference in MABP
      between the OPC-31260 and vehicle treated females. Thus, the present study has
      provided additional evidence for a V2-like receptor related vasodilator effect in
      male rats. However, since female rats do not appear to express a V2-receptor
      mediated vasodilator response, the sexually dimorphic pressor response to
      vasopressin cannot be due to a gender difference in V2-receptor vasodilator
      activity.

PMID- 8761021
TI  - Antibodies directed against the mu-opioid receptor alleviated multiple signs of
      morphine withdrawal in mice.
AB  - An investigation was made into the effect of intracerebroventricular (i.c.v.)
      administration of antibodies to the amino-terminal portion 1-16
      (MDSSTGPGNTSDCSDP) or the peptide sequence 208-216 (TKYRQGSID) of the cloned mu
      opioid receptor (mu-OR) on morphine tolerance and dependence. Animals were
      rendered tolerant-dependent by subcutaneous (s.c.) implantation of an oily
      morphine suspension. To precipitate withdrawal syndrome, the opioid antagonist
      naloxone (1 mg/kg, s.c.) was administered 72 h after chronic morphine treatment.
      In mice i.c.v. injected with the anti-mu-OR antibodies, the analgesic effect of
      chronic morphine was significantly reduced. These antibodies given 24 h before
      starting the chronic morphine treatment, reduced most of the symptoms associated
      with the withdrawal syndrome (jumps, loss of body weight, diarrhoea and body
      shakes) elicited by naloxone in dependent mice. The administration of the
      antisera to mice undergoing 48 h of chronic morphine treatment did not
      precipitate detectable signs of abstinence, but reduced the withdrawal syndrome
      precipitated by naloxone 24 h later. The finding that both antibodies impaired mu
      1/mu 2-mediated effects, suggests a high degree of homology between the
      pharmacologically defined subtypes of mu-OR.

PMID- 8761022
TI  - Dmt-Tic-OH a highly selective and potent delta-opioid dipeptide receptor
      antagonist after systemic administration in the mouse.
AB  - Dmt-Tic-OH (DTOH) and Dmt-Tic-Ala-OH (DTAOH), effective antagonists in vitro,
      represent a new potent opioid dipeptides for the delta-opioid receptor (Ki delta
      of 0.022 nM and a selectivity, Ki mu/Ki delta, of 150,000 for DTOH; Ki delta of
      0.285 nM and a selectivity Ki mu/Ki delta, of 20,4 for DTAOH). In the present
      study we considered the pharmacological activity of these two new delta opioid
      peptide receptor antagonists in vivo. Therefore, we have evaluated their possible
      antagonistic activity against the antinociception induced by the highly selective
      delta opioid receptor agonist, [D-Ala2]deltorphin II (DEL). Furthermore, these
      two delta opioid peptide receptor antagonists were injected centrally or
      peripherally in order to assess their ability to act also after systemic
      administration. Concurrent i.c.v. injection of DTOH or DTAOH (0.5-1.0-2.0 nM)
      with DEL (5 nmol) induced a significant reduction of DEL antinociception. By
      contrast, while DTOH (10-20-40 mg/kg) administered peripherally (i.p., s.c. or
      i.v.) was also able to reduce DEL antinociception, DTAOH failed. The present
      results indicate that DTOH is the first opioid dipeptide with delta antagonist
      activity after systemic administration and it could be important in the clinical
      and therapeutic applications.

PMID- 8761023
TI  - Effects of the synthesized growth hormone releasing peptide, KP-102, on growth
      hormone release in sodium glutamate monohydrate-treated low growth rats.
AB  - KP-102 (D-Ala-D-beta-Nal-Ala-Trp-D-Phe-Lys-NH2), a new second generation
      hexapeptide, has a potent growth hormone (GH)-releasing action in vivo and in
      vitro. Here, we evaluated the GH-releasing action of KP-102 under pentobarbital
      (PB) anesthesia in neonatally sodium-glutamate-monohydrate-treated low growth
      (NMSG-LG) rats. The plasma GH level in NMSG-LG rats after i.v. administration of
      KP-102 at 100 micrograms/kg was 1/6.7 (95% C.L. 1/14.7 - 1/3.0) of that in normal
      rats given the same dose (p < 0.01). However, the increase was significant
      compared with that in normal rats after saline administration (p < 0.01). The
      plasma GH releasing action of KP-102 at 100 micrograms/kg i.v. in rats with
      lesions in the bilateral hypothalamic arcuate nuclei (ARC), was about 1/6.3 (95%
      C.L. 1/12.4 - 1/3.2) of that in normal rats under PB anesthesia (p < 0.01). When
      KP-102 was injected into the ARC at doses of 0.0002, 0.02 and 2 micrograms/rat,
      GH release was dose-related (p < 0.01) under PB anesthesia. KP-102 at 2
      micrograms i.c.v. also increased the plasma GH levels (p < 0.01) to about 1/8.3
      (95% C.L. 1/22.7 - 1/3.1) of that by systematic administration, at the same
      potency as the ARC injection (1/13.7 and 95% C.L. 1/37.2 - 1/5.0). These findings
      suggest that KP-102 potently stimulates the GH release by a direct or indirect
      antagonism of somatostatin (SRIF) and growth hormone releasing hormone (GHRH)
      release in the hypothalamus and by a direct action on the pituitary. Furthermore,
      the GH-releasing action of KP-102 was similar and additive upon both regions in
      vivo at the maximum effective dose. Moreover, since the GH-release in response to
      KP-102 administration differed between NMSG-LG and normal rats, and since KP-102
      increased the GH release even in NMSG-LG rats, it should be evaluated in the
      hypophysial GH secretion tests, and may be used to treat the hypophysial GH
      secretion insufficiency.

PMID- 8761024
TI  - Oxytocin augmentation of gonadotropin-releasing hormone-stimulated luteinizing
      hormone release is modulated by cyclic AMP.
AB  - Oxytocin has been previously shown to augment GnRH-stimulated LH release. However
      it is currently unknown which intracellular mediators participate in the process.
      In this study, after preincubation with oxytocin for 3 hours, quartered
      pituitaries were stimulated for 15 minutes with GnRH. The effects of diBucAMP, a
      cell permeable analog of cAMP, and DDA, an adenyl cyclase inhibitor, on the
      augmentation by oxytocin were investigated. Although addition of diBucAMP
      increased GnRH-stimulated LH release, it inhibited the augmentation by oxytocin
      of the response to GnRH. On the other hand addition of DDA induced an increased
      augmentation by oxytocin. These results indicate that intracellular cAMP inhibits
      the augmentory activity of oxytocin, and suggest that oxytocin modulation of GnRH
      action in vivo would be optimal when the hormonal milieu results in reduced
      levels of cAMP.

PMID- 8761025
TI  - Studies on the immunoglobulin-E system of the common marmoset in comparison with
      human data.
AB  - In the common marmoset (Callithrix jacchus jacchus) immunoglobulin E (IgE) serum
      levels and IgE synthesis of peripheral blood mononuclear cells (PBMC) in vitro
      were investigated in order to look for homologies to the human system. While IgE
      was not found in marmoset blood plasma with three commercial antihuman IgE-kits
      with monoclonal antibodies (mAbs), two other kits using polyclonal antibodies
      against human IgE revealed detectable IgE concentrations of up to 10 kU/liter in
      plasma samples of 19 out of 21 marmosets. In accord with human data, rhIL-4
      showed biological functions under in vitro conditions in PBMC of the New World
      monkey. Proliferation, measured by 3H-thymidine incorporation, of isolated PBMC
      of marmosets could be induced by rhIL-4. FACScan analysis showed an enhanced
      expression of the low affinity IgE receptor CD23 (Fc epsilon RII) on CD20+ B
      lymphocytes after incubation with rhIL-4. Furthermore, PBMC from marmosets could
      be stimulated by IL-4 alone or in combination with dexamethasone as well as with
      lipopolysaccharide (E. coli) to produce IgE in culture. The results indicate that
      Callithrix jacchus is using an IgE system that is rather similar to that of
      humans, although not completely identical. Antihuman mAbs and rhIL-4 can be used
      to investigate IgE regulation in vitro of marmoset PBMC. These data encourage the
      development of a primate animal model for studying possible modifications of the
      IgE system under pathological conditions to find new therapeutic strategies in
      atopic diseases.

PMID- 8761026
TI  - Electrolyte content of serum, erythrocyte, kidney and heart tissue in salt
      induced hypertensive rats.
AB  - The effect of salt load on the systolic blood pressure (SBP) and electrolyte
      levels of serum, erythrocyte, kidney and heart tissue was studied in rats. NaCl
      treatment increased sodium (5.69 +/- 0.4 mmol/L p < 0.001, 149.8 +/- 4.0 mEq/L, p
      < 0.001) and decreased potassium (112.6 +/- 2.4 mmol/L p < 0.001, 5.0 +/- 0.2
      mEq/L, p < 0.001) in red cell and serum respectively. A decreased level of serum
      magnesium (1.4 +/- 0.3 mEq/L, p < 0.005) was observed. Sodium content was
      increased in both heart (39.93 +/- 2.9 mumol/g, p = n.s) and kidney tissues
      (44.39 +/- 0.5 mumol/g, p < 0.001). A pronounced increase in intracellular
      calcium (2.54 +/- 0.2 mumol/g, p < 0.001) and a decrease of magnesium content
      (6.05 +/- 0.8 mumol/g, p < 0.001) was observed in kidney tissue after treatment.
      The results suggested that marked changes in electrolyte levels of erythrocytes,
      serum, heart and kidney tissues in NaCl loaded rats may play a definite role in
      the development of salt induced hypertension.

PMID- 8761027
TI  - Effects of SCN substitution for Cl- on tension, [Ca2+]i, and ionic currents in
      vascular smooth muscle.
AB  - Substitution of thiocyanate ions (SCN-) for chloride ions (Cl-) in the
      extracellular medium of aortic rings and strips causes a biphasic contractile
      response; initial relaxation followed by sustained contraction. Alterations in
      these responses are sex-specific, and may elucidate fundamental differences in
      vascular function between males and females. In order to investigate the role of
      changes in intracellular Ca2+ ([Ca2+]i) in these changes in tension, we
      investigated effects of SCN- on [Ca2+]i and ionic currents in vascular smooth
      muscle cells (VSMC). Extracellular substitution of SCN- for Cl- caused a biphasic
      change in [Ca2+]i. Initially, [Ca2+]i decreased, reaching a minimum within 1-2
      min, subsequently returned to original levels within 4-5 min, and then increased
      to a higher plateau over the next 10 minutes. This pattern of change in [Ca2+]i
      is identical to the pattern of tension changes in aortic rings, but it occurs
      somewhat faster. Partial substitution of SCN- for Cl- elicited increased, but no
      preceding decrease in [Ca2+]i. In the absence of external Ca2+, anion
      substitution elicited the decrease in [Ca2+]i but not the subsequent increase.
      Verapamil (1 microM) blocked the increased [Ca2+]i phase but not the decreased
      [Ca2+]i phase; whereas, R+ verapamil (up to 5 microM for 20 min), an inactive
      enantiomer, caused no change. Ionic current measurements obtained using whole
      cell patch and current clamp techniques revealed two responses to anion
      substitution: (a) a rapid, transient outward shift in holding current, and (b) a
      sustained increase in peak current and a hyperpolarizing shift in voltage
      sensitivity of Ca2+ channels. The calcium channel blocker PN200-110 blocked SCN(
      )-enhanced current but had no effect on the changes in holding current. S-
      verapamil, but not R+ verapamil, reduced SCN(-)-enhanced current. In current
      clamp mode, SCN- caused an initial hyperpolarization followed by a slow
      depolarization punctuated by spikes. Thus, SCN- causes changes in vascular smooth
      muscle [Ca2+]i that could underlie both phases of its effects on tension in
      isolated aortas and may be explained by the following model: an initial outward
      shift in current causes hyperpolarization with a consequent decrease in cell
      excitability, and the somewhat slower increase in Ca2+ channel excitability
      eventually leads to enhanced calcium influx and tension. These data shed light on
      possible mechanisms underlying gender-related differences in VSMC physiology.

PMID- 8761028
TI  - The effects of tropicamide on mydriasis in young rats exhibiting a natural
      deficit in passive-avoidance responding.
AB  - The young rat at post-natal day 18-22 exhibits a natural deficit in passive
      avoidance responding that can be corrected with the acute systemic administration
      of different cholinomimetic drugs, such as tacrine. In order to evaluate the
      generality of this apparent cholinergic hypofunction, different doses of the
      anticholinergic agent tropicamide, were administered either systemically or
      dropped directly into the eye of young or adult rats. Tropicamide produced
      mydriasis in a dose-dependent manner. The ED50 for tropicamide dropped into the
      eye was 0.025% for adult rats and 0.12% for young rats. When doses between 0.3
      and 100 mg/kg were delivered systemically, the mean time course for recovery to
      baseline pupil size was accelerated in young rats. The average time to recovery
      across all doses was 112 +/- 27 min (mean+/-SE) for young rats and 274 +/- 70 min
      for adults. When subcutaneous tacrine was given immediately to young rats after
      training in a passive-avoidance response (PAR) task, retention was enhanced at
      testing 24 hours later in a dose-dependent manner. The response latencies were
      statistically different from saline-treated controls at doses of 0.003 and 0.01
      mg/kg. This was not observed in adult rats. Taken together these results suggest
      that the PAR, along with the mydriacyl response of the young rat to tropicamide,
      may be regulated by a system of subsensitive cholinergic receptors.

PMID- 8761029
TI  - Modulation of erythropoietin production by selective adenosine agonists and
      antagonists in normal and anemic rats.
AB  - Hypoxia or anemia is the fundamental stimulus for erythropoietin (EPO)
      production. Recent in vitro studies suggest that EPO secretion in response to
      hypoxia is regulated by adenosine in the kidney. In order to examine the in vivo
      effect of adenosine on EPO production, we determined the effects of adenosine
      receptor agonists and antagonists on serum EPO concentration in normal and anemic
      rats. In normal rats, intravenous injection of adenosine agonists (NECA, CHA and
      CGS-21680) dose-dependently stimulated EPO production. Pretreatment with KW-3902,
      an adenosine A1 antagonist with modest A2b antagonistic action, or KF17837, an
      adenosine A2a antagonist, inhibited the NECA (0.1 mg/kg, i.v.)-stimulated EPO
      production. Anemic hypoxia, induced by 2% (v/w body weight) blood withdrawal,
      increased serum EPO concentration from 38 +/- 2 to 352 +/- 76 mU/ml, with the
      increased serum adenosine concentration in the renal vein. KF17837 (0.1 mg/kg,
      i.v.), but not KW-3902 (0.1 mg/kg, i.v.), inhibited the anemic hypoxia-induced
      increase in EPO production. The present findings support the notion that
      adenosine mediates the EPO production in response to hypoxia in the kidney.

PMID- 8761030
TI  - Modification of the effects of 7-OH-DPAT, a dopamine D3-receptor agonist, on
      morphine-induced hyperlocomotion by diabetes.
AB  - We examined the effect of 7-OH-DPAT on spontaneous locomotor activity that is
      enhanced in diabetic mice. 7-OH-DPAT (0.1-30 mg/kg, s.c.) dose-dependently
      decreased the enhanced spontaneous locomotor activity in diabetic mice, but not
      in nondiabetic mice. When mice were pretreated with of 7-OH-DPAT (0.1 mg/kg),
      morphine-induced enhanced locomotor activity in nondiabetic mice, but not in
      diabetic mice, was significantly reduced. Furthermore, 7-OH-DPAT (0.1 mg/kg)
      significantly attenuated the morphine-induced increase in DA turnover in both
      nondiabetic and diabetic mice. However, DA turnover was significantly greater in
      diabetic mice than in nondiabetic mice. Thus, it is likely that the enhanced
      spontaneous locomotor activity in diabetic mice may be partially related to the
      down-regulation of D3-receptor-mediated modulation of dopamine release in the
      limbic area.

PMID- 8761031
TI  - Inhibitory effect of lithium on cAMP dependent phosphorylation system.
AB  - The aim of the present study was to assess the direct effect of lithium on cAMP
      dependent phosphorylation. The results show that lithium, but not rubidium, at
      therapeutic and high concentrations significantly decreases the cAMP stimulated
      MAP2 endogenous phosphorylation in microtubule fraction. An inhibitory effect of
      lithium has also been found using purified heat stable microtubule proteins
      phosphorylated by the catalytic subunit of PKA. These data suggest a direct
      effect of lithium on the cAMP dependent protein kinase.

PMID- 8761032
TI  - Effects of beraprost sodium, a prostacyclin analogue, on tail flick response in
      two models of diabetic-neuropathy in rats and its mechanism.
AB  - The effects of beraprost sodium (BPS), a stable prostacyclin analogue, on the
      tail flick (TF) latency were investigated in streptozotocin-induced (STZ;55mg/kg,
      i.p.) diabetic male Sprague-Dawley (SD) rats and in spontaneously diabetic
      WBN/Kob rats. The SD rats were divided into 5 groups, i.e., (I) normal, (II)
      diabetic control, diabetic treated with (III) BPS (10 micrograms/kg/day), (IV)
      BPS (30 micrograms/kg/ day), and (V) aldose reductase inhibitor (ARI; epalrestat,
      50 micrograms/kg/day). The drugs were administered orally. At 12 weeks, TF
      latency was significantly longer in untreated diabetic rats than in normal rats.
      After 4 weeks treatment, BPS significantly improved the abnormality in TF latency
      dose-dependently. But ARI did not normalize the response. The 45 weeks male
      WBN/Kob rats were divided into 2 groups: diabetic control and diabetic treated
      with BPS at 30 micrograms/kg/day, p.o., respectively. Untreated, age-matched
      wistar rats were served as the normal group. At 61 weeks, TF latency was
      significantly longer in control WBN/Kob rats than in normal wistar rats in time
      dependent manner. After 16 weeks treatment, BPS significantly normalized the
      prolongation in TF latency. In in vivo experiments, BPS significantly increased
      the cyclic AMP (cAMP) content in sciatic nerves from normal rats dose
      dependently. In STZ-induced diabetic rats, cAMP content in sciatic nerves were
      significantly reduced, and 4 weeks treatment of BPS significantly restored this
      reduced cAMP content. It was suggested that BPS may be effective on diabetic
      neuropathy by, at least in part, maintenance of cAMP contents in the nerves.

PMID- 8761033
TI  - Endothelin-1 secretion from cultured vascular endothelial cells of DOCA-salt
      hypertensive rats.
AB  - The profile of endothelin-1 (ET-1) release from cultured vascular endothelial
      cells (ECs) obtained from deoxycorticosterone acetate (DOCA)-salt hypertensive
      rats, was examined and compared with that from normotensive sham rats. ET-1
      release from ECs was increased in a time-dependent manner, and the level of DOCA
      salt hypertensive rats was higher than that of sham rats. Incubation of ECs with
      transforming growth factor (TGF)-beta 1 or thrombin resulted in a significant
      increase in the ET-1 release, while FK409, a novel nitric oxide donor, produced a
      dose-dependent decrease in the release. In the case of ECs from DOCA-salt
      hypertensive rats, the potencies of TGF-beta 1- or thrombin-induced action was
      much less than that seen with sham rats, while the difference of reactivity to
      FK409 was not observed between ECs of DOCA-salt rats and sham rats. Thus, ET-1
      production in ECs appears to be up-regulated in DOCA-salt hypertensive rats. In
      addition, there seems to be an abnormalities in the signaling pathway via TGF
      beta 1- or thrombin-induced enhancement of ET-1 production in ECs of DOCA-salt
      hypertensive rats.

PMID- 8761034
TI  - Flunitrazepam effects on human sleep EEG spectra. II: Sigma and beta alterations
      during NREM sleep.
AB  - Flunitrazepam (FNZ) is known to enhance the higher EEG frequencies, including
      sigma (10-15 Hz) and beta (20-28 Hz). Both sigma and beta frequency bands show an
      inverse relationship with delta (0.3-3 Hz) during NREM periods, as we have
      previously reported. It is not known whether generation of these two EEG
      frequencies is mediated by the same or different neuronal mechanisms. In this
      report, we compare alterations of delta, sigma and beta EEG induced by FNZ (4 mg)
      orally administered to five healthy male subjects for seven consecutive nights.
      Sleep EEG on the baseline night (BLN), and the fourth and seventh drug nights
      (4DN, 7DN) was subjected to fast Fourier transform (FFT) analysis. On drug
      nights, sigma was enhanced without regard to delta amount, but beta was enhanced
      only during epochs containing low delta. Thus, sigma and beta EEG were altered
      differently by the same pharmacological agent. These results suggest that sigma
      and beta EEG are mediated by different neuronal mechanisms.

PMID- 8761035
TI  - Short latency facilitation between pairs of threshold magnetic stimuli applied to
      human motor cortex.
AB  - Pairs of threshold magnetic stimuli were applied over the motor cortex at
      interstimulus intervals of 1-6 ms, and EMG responses recorded from the relaxed or
      active first dorsal interosseous muscle of 7 normal subjects. In relaxed
      subjects, when the interval between the stimuli was around 1.0-1.5 ms, 2.5-3.0 ms
      or 4.5 ms or later, the size of the response to the pair of stimuli was much
      greater than the algebraic sum of the response to each stimulus alone. During
      contraction, fewer peaks of facilitation were observed. Facilitation was evident
      if the stimuli were 0.9-1.1 times threshold in the relaxed state, and 1.0-1.1
      times threshold during voluntary contraction. Experiments using either magnetic
      followed by anodal electric stimulation, or pairs of anodal electric stimuli,
      suggested that the facilitation most likely occurred within the cerebral motor
      cortex. Given the timings at which facilitation is prominent, it seems likely
      that it reflects interactions between circuits normally responsible for
      production of I-waves.

PMID- 8761036
TI  - Enhancement of inhibitory mechanisms in the motor cortex of patients with
      cerebellar degeneration: a study with transcranial magnetic brain stimulation.
AB  - The excitatory state of the primary motor cortex can be studied by measuring
      either the postexcitatory inhibition after transcranial magnetic single
      stimulation (pI-S) or the refractory period with magnetic double stimulation (rP
      D). The cerebellum may influence the excitability of the motor cortex by
      cerebellar inputs and outputs from side loops of transcortical projections.
      Therefore, we studied pI-S and rP-D in 24 patients with autosomal dominant
      cerebellar ataxia or idiopathic cerebellar ataxia, who were allocated to one
      group (Group A) with mild to moderate ataxia (n = 11) and to another group (Group
      B) with severe ataxia (n = 13). The results were compared with those obtained in
      21 normal age-matched control subjects. The central motor conduction time (CMCT)
      was delayed in approximately half of the patients, demonstrating that the
      degenerative process, beyond the cerebellum, also affects the pyramidal tract.
      Mean CMCT was significantly delayed only in patients of Group B. pI-S was
      prolonged in 10 of our 24 patients; incidence of pathology in pI-S did not differ
      between the two patient groups. In 5 patients with normal CMCT, pathological pI-S
      results were found. Mean pI-S was prolonged in the whole patient group and in
      both subgroups as well. rP-D was prolonged in two patients of Group B only, but
      mean rP-D was significantly prolonged in the whole patient group. Prolonged
      postexcitatory inhibition and refractory period may be a consequence of a
      transient facilitation of cortical inhibitory interneurons, which results in a
      decreased excitability of primary motor cortex in patients with cerebellar
      degeneration.

PMID- 8761037
TI  - Central changes in muscle fatigue during sustained submaximal isometric voluntary
      contraction as revealed by transcranial magnetic stimulation.
AB  - Changes in responses to transcranial magnetic stimulation (TMS) during submaximal
      isometric voluntary contraction (60% of maximal voluntary contraction (MVC) of
      the adductor pollicis muscle and the subsequent recovery period have been studied
      in healthy volunteers. TMS at twice the motor threshold was applied during the
      sustained contraction, as well as at rest and during short-lasting (2 s) 60% MVCs
      before and immediately after the sustained contraction, and at 5 min intervals
      during the recovery period. Both motor evoked potential (MEP) magnitude (peak and
      area) and silent period (SP) duration in electromyographic activity (EMG) of the
      adductor pollicis muscle showed a gradual decrease up to the endurance point and
      an increase thereafter. MEPs elicited at rest immediately after the fatiguing
      contraction were larger, whereas those elicited later on during the recovery
      period did not differ significantly from the controls. It is suggested that the
      changes in responses to TMS, divergent from those in ongoing voluntary EMG during
      the sustained 60% MVC, indicate complex processes at levels preceding the motor
      cortex output cells in an attempt to maintain a submaximal contraction of the
      fatigued muscle. The increase in MEP magnitude after the sustained 60% MVC may
      indicate residual changes in cortical activity after fatiguing contraction.

PMID- 8761038
TI  - Facilitation of motor evoked potentials by postcontraction response (Kohnstamm
      phenomenon).
AB  - We have applied repeated transcranial magnetic stimuli during the involuntary
      postcontraction muscle activity (Kohnstamm phenomenon) or during a tonic
      vibration reflex, both presumably arising from subcortical levels. The motor
      evoked potentials (MEPs) were compared with the MEPs evoked during a comparable
      voluntary contraction (cortical origin). The MEP amplitudes from the deltoid
      muscle appeared linearly related to the mean amplitude of the smoothed rectified
      background EMG preceding the stimulus. No differences in the facilitatory effect
      between voluntary and involuntary preinnervation manoeuvres were found. If we
      accept the hypothesis of a subcortical origin of the involuntary muscle activity
      in the Kohnstamm phenomenon, the similar facilitatory effect of involuntary and
      voluntary background EMG supports a predominantly spinal localisation of the
      facilitatory mechanism in this proximal muscle both during involuntary and during
      voluntary activity, at least under the present conditions of rather low stimulus
      strengths. In about 20-30% of all the trials an extra facilitatory effect on the
      MEP amplitude was observed during the shortening contraction compared to an MEP
      elicited during the lengthening contraction, in spite of a similar background
      EMG. This extra facilitatory effect of the shortening contraction was observed
      during involuntary and voluntary preactivation, suggesting an elevated excitatory
      state at the spinal level.

PMID- 8761039
TI  - Postexcitatory inhibition after transcranial magnetic single and double brain
      stimulation in Huntington's disease.
AB  - Postexcitatory inhibition (pI) was studied in 13 patients with different clinical
      forms of Huntington's disease (HD), using a transcranial magnetic single and
      double stimulation paradigm. We found pathological results of pI in 77% of the HD
      patients. A significant prolongation of pI could be demonstrated in the group of
      patients suffering from a classical form of HD. In contrast to these patients,
      those patients suffering from primary rigid HD variants exhibited a shortening of
      pI. These results suggest an altered excitability of the motor cortex in HD
      according to dysfunctions within the motor cortex-basal ganglia loop.
      Transcranial double stimulation was a more sensitive measure in detecting changes
      of cortical excitation levels than single stimulation. The interpretation of pI
      changes in HD has to take the clinical subtype of HD into account.

PMID- 8761040
TI  - Central nervous system plasticity after spinal cord injury in man: interlimb
      reflexes and the influence of cutaneous stimulation.
AB  - In persons who have sustained severe injuries to the cervical spinal cord,
      electrical stimulation of mixed peripheral nerves in a lower limb can evoke short
      latency, bilateral motor responses in muscles of the distal upper limbs; such
      motor responses have been termed interlimb reflexes. In the present study, we
      investigated the role that cutaneous stimulation plays in evoking interlimb
      reflexes. Fifteen subjects with chronic injury (> 1 year) to the cervical spinal
      cord were investigated. Single motor unit activity was recorded from a number of
      distal upper limb muscles. The lower limb cutaneous area within which stimulation
      recruited a given motor unit of the upper limb was defined as that motor unit's
      'receptive field'. Activity from a total of 48 single motor units was analyzed.
      The majority of motor units responded to light touch, individual hair movement,
      and thermal (hot and cold) stimulation. Excitatory responses were observed
      bilaterally, although contralateral responses predominated. Stimulation
      occasionally resulted in inhibition of a spontaneously active motor unit.
      Receptive fields varied a great deal in size, with proximal locations being
      larger than those encountered in more distal lower limb locations (i.e. the
      toes). The spinocervical tract is a possible candidate for mediating some portion
      of these interlimb reflexes, the origin of which may be due to new growth
      (regenerative sprouting) in the spinal cord caudal to a severe injury.

PMID- 8761041
TI  - Contralateral and ipsilateral EMG responses to transcranial magnetic stimulation
      during recovery of arm and hand function after stroke.
AB  - We examined the relationship between the recovery of hand and arm function in a
      group of hemiplegic stroke patients and the presence of short-latency EMG
      responses to transcranial magnetic stimulation (TMS) in 4 different upper limb
      muscles (deltoid, biceps, extensor digitorum communis and the first dorsal
      interosseous). Twenty-one patients were examined within 5 weeks of stroke (median
      2 weeks), and then at regular intervals over the next 12 months. Some patients
      recovered rapidly (Group A); in others, recovery was slow and incomplete (Group
      B). Even at the first test, Group A patients had responses to TMS in all muscles.
      Most Group B patients initially lacked responses in all tested upper limb
      muscles; in those that later were able to activate hand muscles, responses
      returned at or just before this stage of recovery. No such clear correlation
      between the presence of responses to TMS and ability to activate more proximal
      arm muscles was evident. Response latency was initially long and declined in a
      manner that was highly correlated with muscle strength and hand function test
      scores. Ipsilateral responses were elicited from both the affected and unaffected
      hemispheres. Ipsilateral responses from the latter were most common in the
      proximal muscles of the affected limb, and had latencies that were longer than
      those elicited in the contralateral (unaffected) arm. Nine cases of ipsilateral
      responses in hand muscles were found; such responses are not found in healthy
      subjects. Ipsilateral responses from the undamaged hemisphere were more prevalent
      in the poorly recovered patients; the underlying mechanisms may not be beneficial
      for recovery.

PMID- 8761042
TI  - Voluntary contraction shortens peripheral conduction time in response to
      transcranial magnetic stimulation of the brain.
AB  - We investigated the effects of voluntary contraction on peripheral conduction
      time in response to transcranial magnetic stimulation (TMS) of the brain in 10
      normal subjects. We obtained surface recordings of compound muscle action
      potentials (CMAP) from the abductor digiti minimi muscle (ADM) and nerve action
      potentials (NAP) from the ulnar nerve, at rest and during contraction (10% of
      maximal voluntary contraction) in response to TMS delivered at 100% output using
      a coil shaped like a figure 8. The distance between the two recording electrodes
      was 10 cm. The distal latency in response to TMS was calculated by subtracting
      the NAP latency from the CMAP latency. Distal latency was also measured by
      recording ADM responses to supramaximal electrical stimulation (ES) 10 cm
      proximal to the recording electrode. TMS-induced distal latency was significantly
      shorter during voluntary contraction than at rest (P < 0.0001). There was no
      significant difference between TMS-induced distal latency during contraction and
      ES-induced distal latency. TMS-induced distal latencies at rest and during
      contraction were correlated with the ES-induced distal latencies (r2 = 0.468, P =
      0.028 and r2 = 0.769, P = 0.0009, respectively). Our results showed that the
      peripheral conduction time in response to TMS was related to the activity of the
      target muscle and to the fastest conduction velocity of the target nerve.
      Voluntary contraction reduced the peripheral conduction time in response to TMS.

PMID- 8761043
TI  - Recurrent inhibition of soleus alpha-motoneurons during a sustained submaximal
      plantar flexion.
AB  - During 10 min of sustained isometric plantar flexion at 20% of maximal voluntary
      contraction, recurrent inhibition of soleus alpha-motoneurons was studied in 9
      healthy subjects (age 22-37 years). Recurrent inhibition was brought about by a
      conditioning H-reflex and assessed by a test H-reflex delivered 10 ms later. The
      amplitude of the test H-reflex during the tenth minute of the contraction (16.9
      +/- 13.2% of the maximal compound motor action potential) was significantly
      increased as compared to that during the first minute (9.8 +/- 7.6%), while the
      conditioning H-reflex remained unchanged. Concomitantly, muscle fatigue was
      evidenced by a significant increase in amplitude of the soleus electromyogram.
      The increase of the test-H-reflex amplitude implies that a decrease in recurrent
      inhibition occurred during the sustained submaximal contraction, which contrasts
      results from studies on maximal voluntary contractions. These results indicate a
      modulation of soleus Renshaw interneurons, which is likely to serve the purpose
      of optimising motor unit recruitment and firing rates of this muscle during a
      sustained submaximal contraction.

PMID- 8761044
TI  - Task-dependent effects evoked by foot muscle afferents on leg muscle activity in
      humans.
AB  - The effect of low intensity electrical stimulation of the posterior tibial nerve
      (PTN) at the ankle on the active triceps surae (TS) muscles was studied in normal
      subjects, both in a prone position and while standing. PTN stimulation regularly
      evoked the H-reflex in the flexor digitorum brevis and, in the prone position, a
      short-latency facilitatory effect in the soleus muscle. During standing, the
      facilitatory effect was preceded by a clear-cut reduction in electromyograph
      (EMG) activity. The inhibition-facilitation sequence was evoked in the
      gastrocnemii under both conditions, on average, though individual differences
      were present. An EMG modulation similar to that observed under standing
      conditions was present also in the prone position when subjects pressed the sole
      of the foot against the wall. Stimulation of sural or digital nerves did not
      evoke similar effects. It is concluded that foot muscle afferents establish
      oligosynaptic connections transmitting mixed effects to the TS motoneuronal pool,
      and that contact with the sole of the foot plays an enabling role for the
      inhibitory pathway directed to the soleus muscle.

PMID- 8761045
TI  - The R3 component of the blink reflex: normative data and application in spinal
      lesions.
AB  - The clinical value of the R3 component (R3) of the blink reflex (BR) for
      differentiating between lesions at the medulla oblongata and cervical spinal cord
      level is still unclear. In 50 healthy volunteers (25 women, 25 men, aged 20-75
      years) reproducible ipsi- and contralateral R3 responses could be evoked showing
      a mean onset latency of 84 ms, a duration of 32 ms and a side-to-side difference
      of almost 3 ms. The latency increased with age. Eleven patients with lesions of
      the cervical spinal cord (segments C1-C6) showed normal R3 latencies. In 4
      patients with pathology of the brain-stem, however, R3 was abnormal, showing
      identical changes as observed with the R2 component. Our results suggest that the
      reflex arc of R3 does not descend to the cervical spinal cord but within the
      brain-stem possibly takes the same connections as the R2 component.

PMID- 8761047
TI  - IFCN recommended standards for electrophysiologic monitoring in comatose and
      other unresponsive states. Report of an IFCN committee.

PMID- 8761046
TI  - Wrist tremor: investigation of agonist-antagonist interaction by means of long
      term EMG recording and cross-spectral analysis.
AB  - We have developed a method to observe and quantify the phasic relationship
      between the burst patterns of antagonistic muscles in any roughly periodic
      movement, such as tremor, for up to 24 h. This paper describes our approach, in
      which long-term EMG recordings are evaluated by a procedure based on cross
      spectral analysis. The method is then illustrated by data from 6 patients with
      essential tremor. Our data confirm earlier observations that a particular patient
      may show different burst patterns at different times. However, as opposed to
      tremor analysis based on short-term recording, our method allows quantitative
      statements on the relative frequency of the burst patterns, as they occur under
      everyday conditions. In addition, our data suggest that in ET (a) alternating
      tremor activity in one hand may occur simultaneously with synchronous activity in
      the other hand; (b) along with the classical alternating and co-contracting
      patterns there may be significant 'non-classical' activity, that cannot be called
      alternating or synchronous.

PMID- 8761048
TI  - Prognostic significance of quantitative electroencephalography in Alzheimer
      patients: preliminary observations.
AB  - In 31 Alzheimer outpatients followed up for a mean time of 26.4 months the
      hypothesis that quantitative electroencephalography (qEEG) could predict the loss
      of activities of daily living (ADL), the onset of incontinence, and death was
      tested by the Weibull proportional hazard model of 'lifereg' procedure of the
      Statistical Analysis System package. A central-posterior temporal region was
      considered in either side (power-weighted, log transformed relative values).
      Right delta predicted both the loss of ADL and death, whereas right theta
      predicted the onset of incontinence. Left values gave borderline significant
      results toward all end-points, whereas power-weighted mean frequency always gave
      borderline results. The curves calculated for predicted times may be a valid
      support for the clinician in attempting prognostic judgments of disease
      evolution.

PMID- 8761049
TI  - A comparison of EEG signal dynamics in waking, after anesthesia induction and
      during electroconvulsive therapy seizures.
AB  - Evidence suggests that quantitative dynamical measures of electroencephalogram
      (EEG) signals are more appropriate for characterizing the differences between
      states in an individual rather than as absolute indices. One such measure, the
      largest Lyapunov exponent (lambda 1), appears to have potential for identifying
      seizure activity and for being of clinical utility for characterizing
      electroconvulsive therapy (ECT) seizures. As a result, we compared lambda 1 for
      the EEG recorded in 8 depressed subjects in 3 states: (1) during right unilateral
      ECT seizures, (2) during the pre-ECT waking state, and (3) following anesthesia
      administration but prior to ECT. Spectral amplitude and autocorrelation were also
      calculated in these states, allowing a comparison of these measures with lambda
      1. We hypothesized that lambda 1 would be lowest during the ECT seizures,
      suggestive of greater EEG signal predictability over time during the seizures. We
      found that during the seizures lambda 1 was smaller, while spectral amplitude was
      larger. Significant inter-state differences were not found for the left temporal
      and occipital regions suggesting that these measures might serve as markers of
      the degree of seizure involvement of specific brain regions. Spectral amplitude
      and lambda 1 were uncorrelated and varied independently in some cases. The
      autocorrelation time was shortest in the waking EEG, and longest for the post
      anesthesia EEG, and did not account for the differences seen in lambda 1. In
      contrast, the persistence of oscillations in the autocorrelation functions was
      greater for the ictal EEG than the other two states and may relate to lambda 1.

PMID- 8761050
TI  - Magnetoencephalographic analysis of cortical myoclonic jerks.
AB  - We studied the pre-myoclonus spike using magnetoencephalography in patients with
      cortical myoclonus (6 with cortical reflex myoclonus and one with epilepsia
      partialis continua). The spike was estimated as a single current dipole on the
      pre-central gyrus in one patient with epilepsia partialis continua. In contrast,
      it was estimated as a single dipole on the post-central gyrus in 5 of 6 patients
      with cortical reflex myoclonus, and as two dipoles on the pre- and post-central
      gyrus in the remaining patient. We conclude that there are 3 physiological types
      of cortical myoclonus: (1) abnormal discharges in the motor cortex produce the
      myoclonus; (2) the source of the myoclonus is mainly the sensory cortex; (3) both
      the motor and sensory cortices play important roles in the production of
      myoclonus.

PMID- 8761051
TI  - The interaction of stimulus- and response-related processes measured by event
      related lateralizations of the EEG.
AB  - The present study focused on the relationship between movement- and stimulus
      related asymmetries of the electroencephalogram (EEG). In seven tasks the same
      bilateral stimuli containing asymmetric information were presented but response
      requirements differed. Three functionally distinct asymmetries were found: (1) an
      asymmetry over the motor cortex prior to unimanual movements, (2) an asymmetry
      over the posterior cortex beginning about 20 ms after the start of the movement,
      and (3) an early increase of negativity contralateral to a relevant stimulus (200
      300 ms after stimulus onset) that was maximal at temporo-parietal sites but was
      also visible at central sites. Although related to stimulus side, this asymmetry
      was modulated by response requirements: it was largely abolished with simple
      responses, smaller with nogo than with Go stimuli and occurred twice when a
      sequence of simple and choice responses was required. Therefore, the early
      temporo-parietal asymmetry most probably reflects an interface between sensory
      and movement-related processes.

PMID- 8761052
TI  - Optimal reference electrode selection for electric source imaging.
AB  - One goal of recording voltages on the scalp is to form images of electrical
      sources across the cerebral cortex (electric source imaging). In this study, an
      objective criterion is introduced for selecting the optimal location for the
      reference electrode to attain the maximum spatial resolution of the source image,
      for example as provided here by the truncated singular value decomposition pseudo
      inverse solution. The head model features a realistic cortex within a 3-shell
      conductive sphere, and pyramidal cell activity is represented by 9104 normal
      current elements distributed across the cortical area. On the scalp, 234
      electrodes provide the measurements with respect to a chosen reference electrode.
      The effects of the reference electrode when located at the mastoid, occipital
      pole, vertex or center of the head are analyzed by a singular value decomposition
      of the lead field matrices. Sensitivity to noise, and hence the spatial
      resolution, is found to depend on characteristics of the lead field matrix that
      are determined by the choice of the image source surface, electrode array and
      location of the reference electrode. Using a reference close to a source surface
      increases the sensitivity of the measurement system in identifying the nearby
      activity of low spatial frequency content. However, this feature is compromised
      by a reduction in spatial resolution for distant cortical areas due to noise in
      the measurements. A new performance measure, the image sensitivity map, is
      introduced to identify the cortical regions that provide peak image sensitivity.
      This measure may be exploited in designing the geometry of an electrode array and
      selecting the location of the reference electrode to follow the activity on a
      specific area of the cortical surface.

PMID- 8761053
TI  - The effects of handedness and type of movement on the contralateral preponderance
      of mu-rhythm desynchronisation.
AB  - Event-related desynchronisation (ERD) of mu-rhythm was studied in 12 right-handed
      and 11 left-handed subjects during brisk and slow self-paced index finger
      movements of dominant and nondominant hand. Electroencephalogram (EEG) was
      recorded from the sensorimotor hand area of both hemispheres. The contralateral
      preponderance of mu-rhythm ERD in the pre-movement period showed the following
      changes: (i) the contrasts between left- and right-finger movements were larger
      and earlier in the dominant than nondominant hemisphere in both handedness
      groups; (ii) right-handed subjects showed larger lateralisation of mu-rhythm ERD
      prior to right-finger as compared to left-finger movements, whereas about equal
      contralateral preponderance for both sides was found in the left-handed; (iii)
      the lateralisation of mu-rhythm ERD was lower prior to brisk as compared to slow
      movements, especially in the left-handed subjects. The results demonstrate that
      hand dominance, handedness and type of movement influence the proportion of pre
      movement mu-rhythm desynchronisation in the left and right peri-rolandic area.

PMID- 8761054
TI  - Linear estimation discriminates midline sources and a motor cortex contribution
      to the readiness potential.
AB  - Spatiotemporal dipole modelling of the generators of the readiness potential (RP)
      prior to voluntary movements has yielded diverging results concerning the
      contributions of supplementary motor area (SMA) and primary motor cortex. We
      applied an alternative approach (i.e. linear estimation theory) to measurements
      of the RP preceding fixed and freely selected finger movements, measured at 28
      electrodes of the extended 10-20 system. The volume conductor properties of the
      head were modelled by 3 concentric spheres. Current densities were reconstructed
      on a spherical surface, placed at a depth of 5 mm from the inside of the skull.
      Lead field normalization was applied. The analysis shows activity on the midline
      as well as near the primary motor area. Although some features of the
      reconstructions are not readily interpretable, separate contributions of midline
      sources (including presumably SMA) and motor cortex to the RP are clearly
      distinguished.

PMID- 8761055
TI  - Comparison of late components in simultaneously recorded event-related electrical
      potentials and event-related magnetic fields.
AB  - We have attempted to define the late components of the event-related magnetic
      field (ERF) and to relate them to the late components of the event-related
      electrical potential (ERP). Simultaneous multichannel electroencephalogram (EEG)
      and magnetoencephalogram (MEG) were recorded in 13 subjects during an auditory
      oddball paradigm in two series of experiments. EEG responses to frequent tones
      consisted of the N1 and P2 components of the auditory vertex potential. Responses
      to rare tones consisted of N1, apparent P2, N2 and P3 components. All EEG
      components were best seen in the midline and were highly reproducible for all
      subjects. MEG responses to frequent tones consisted of N1m and P2m components
      that were highly reproducible only when recorded over the temporal region. By
      contrast, the ERF to rare tones was less well defined and only the N1m component
      could be identified satisfactorily. There was little consistent activity in the
      MEG at the time of occurrence of the N2 and P3 components of the ERP.

PMID- 8761056
TI  - [Neurocutaneous flap of the external saphenous nerve. A safe, easy and fast
      procedure for covering loss of substances of the ankle. A propos of 5 cases].
AB  - The distally based sural neurocutaneous flap is another procedure to cover the
      heel. It is an island flap based on the vascular axis of the sural nerve in the
      lower two thirds of the leg. The nerve is included in the pedicle after proximal
      section (it is therefore not a sensitive flap). The size of the flap, length of
      the pedicle, absence of vascular sacrifice, the simple procedure, and minor
      consequences at the donor site led us to use this technique five time over on
      period of four months with success.

PMID- 8761057
TI  - [Therapeutic possibilities of the lateral supra-malleolar flap and its
      variations. Apropos of 6 clinical cases].
AB  - The distally based lateral supramalleolaire flap with a retrograde blood flow on
      the perforating branch of the peroneal artery is a good flap to treat loss of
      skin involving the ankle, the region behind the Achilles tendon, and the foot.
      Based on the results of an anatomical study, the authors describe a modification
      of this flap which can be raised on the infero-lateral collateral artery, with an
      anterograde blood flow. In fact, clinical experience of six cases shows that
      vascular pedicle component (perforating branch of the peroneal artery, infero
      lateral collateral artery) and blood flow (anterograde, retrograde) can be
      calculated according to the regional vascular network, arc of rotation and the
      type of flap. Because of the many possible combinations, it can be considered to
      be a flap with variable vascular pedicle raised "a la carte". However, according
      to our clinical cases, the anterograde blood flow does not seem to have resolved
      the problems of venous congestion of this flap.

PMID- 8761058
TI  - [Cover of the Achilles tendon by peroneus brevis and flexor hallucis longus
      flaps. Apropos of 5 clinical cases].
AB  - Exposure of the Achilles tendon may be secondary to injury, trophic ulceration or
      surgical management of Achilles tendon rupture. We used peroneus brevis (PB) and
      flexor hallucis longus (FHL) muscle flaps to cover the Achilles tendon. The
      muscular portion of these muscles extends very distally, allowing their
      transposition to the Achilles region. PB and FHL are narrow (about 4
      centimeters); the use of both muscles increases their possibilities of coverage.
      We used PB alone in one case and both muscles in four cases. In every case we
      obtained a good functional and cosmetic result. Various fascio-cutaneous flaps
      have been described for the reconstruction of the Achilles region. When there is
      an infection, muscle flaps are preferable to fascio-cutaneous flaps because they
      provide well vascularized tissue. We consequently suggest the use of PB and FHL
      to cover the Achilles tendon when it has been exposed for a long time or when it
      is infected. It seems especially indicated when skin necrosis occurs after
      surgical management of Achilles tendon rupture.

PMID- 8761059
TI  - [Fasciocutaneous flap of the posterior surface of the thigh with distal pedicle.
      Anatomical study and surgical value. A propos of 3 cases].
AB  - In the light of previous studies, the authors conducted an anatomical study on 21
      cadaveric dissections with injection in order to define the characteristics of
      the distally based fasciocutaneous flap of the posterior surface of the thigh,
      described for the first time in 1988 by Maruyama. This leaf-shaped flap extends
      from the popliteal region to the gluteal sulcus. It possesses an axial arterial
      network derived from the popliteal artery, reinforced by the perforating arteries
      derived from the vessel or the profunda femoris artery. The venous return is
      ensured by venae comitantes and the communicating saphenous vein. The flap
      raising technique is described. From 1991 to 1994, 3 patients were operated in
      order to cover a defect of the knee (1 case) and amputation stumps (2 cases). The
      postoperative course was uneventful and the results were considered to be stable
      and of excellent quality with a follow-up of 2 to 4 years.

PMID- 8761060
TI  - [Use of tissue expansion on defective amputation stumps of the lower limbs.
      Apropos of 5 cases].
AB  - Skin flaps are usually required to cover amputation stumps, especially below the
      knee. Cross-leg flaps or free flaps can be used when local tissue is
      insufficient, but as emphasized by Rees in 1986, tissue expansion offers another
      interesting possibility for local coverage. The risk of complications, especially
      infection, in below-knee tissue expansion is well known, requiring rigorous
      patient selection based on an evaluation of skin quality, vascularization, and
      the patient's metabolic and psychologic status. We used this method in 5 patients
      (3 females, 2 males; mean age 30.4 years) who had been amputated below (n = 4)
      and above (n = 1) the knee. In 4 cases, amputation of a healthy limb was required
      after trauma and in 1 case due to purpura fulminans. Seven tissue expanders were
      used with slow intermittent expansion applied daily. The mean expansion period
      was 89.4 days. Mean hospital stay for the two operations was 5.66 and 7.33 days,
      respectively. Assessed on the basis of subjective and objective criteria,
      functional outcome was excellent in 3 patients and good in one patient. Failure
      occurred in one case due to infection. Despite the longer treatment period,
      tissue expansion for skin coverage of defective amputation stumps appears to have
      several advantages. It is a simple, reliable and reproducible method with a
      minimal scar area while preserving skin sensitivity. In addition, the length of
      the tibial shaft can be spared and minimal modifications are needed to fit the
      prosthesis.

PMID- 8761061
TI  - [Cutaneous expansion at the level of the lower limbs. Surgical technique,
      indications and complications].
AB  - Skin expansion in the lowers limbs has been described for a long time. The
      authors report their experience in this site. The operating technique is
      described in such a way as to limit complications to a minimum. The indications
      for this technique are recalled with particular emphasy on the use of expansion
      in preparation for a subsequent procedure. Lastly, the most frequent
      complications are discussed together with the methods of their prevention.

PMID- 8761062
TI  - [The folded fibula flap: anatomical study and clinical application to septic post
      traumatic femoral reconstruction. A propos of 6 cases].
AB  - The reconstruction of extensive femoral defects, particularly septic, by
      revascularized free fibula flap has become part of routine practice for many
      years. Following the demonstration of secondary stress fractures, splitting of
      the fibula into two vascularized barrels was proposed in 1987 to avoid this
      complication. The authors conducted an anatomical study on 100 dry bones in order
      to define the situation of the fibular foramen which is usually found at about
      1.45 cm from the midpoint of the fibula. This foramen must be spared during the
      intermediate splitting osteotomy in order to obtain two bone barrels: one with a
      double centromedullary and periosteal blood supply which will be used like a
      contromedullary pin, and the other with only a periosteal blood supply, which
      will be used as a medial or lateral splint. The deductions concerning the
      preoperative strategy and splitting technique are explained as a function of the
      length of the defect. From 1989 to 1993, 6 male patients underwent extensive
      femoral reconstruction (average length of 9.8 cm). Four free revascularized
      transfers were performed, including one osteocutaneous flap. In two cases, the
      osteocutaneous transfer was a proximally based island pedicle flap. Apart from
      one patient who was subsequently amputated, five patients underwent a secondary
      autologous bone graft after an average of three months. Consolidation was
      achieved after a mean of 12.6 months. A secondary stress fracture was observed in
      one case. With a minimum follow-up of two years, all patients are able to walk
      with a mean shortening of 2 cm of the reconstructed limb and without any donor
      site sequelae.

PMID- 8761063
TI  - [An experimental short-term study of intramuscular integration of macroporous
      biphasic calcium phosphate ceramics. Application to the achievement of
      biocomposite flaps].
AB  - The aim of this research is to prefabricate a bicomposite flap, which can be
      defined as a composite structure of foreign material and living tissue. An animal
      model was developed by vascularizing spherical implants of macroporous biphasic
      calcium phosphate by a latissimus dorsi muscle flap in rabbits. The experiment
      was divided into three stages to compare the role of blood flow in the flap and
      autologous marrow bone cells. Biological apatite precipitation inside the
      macropores requires both factors and allows further clinical applications.

PMID- 8761064
TI  - [Reconstruction of the anterior chest wall by a sandwich-type combination of a
      synthetic support and a muscle flap from the latissimus dorsi. Apropos of a
      case].
AB  - Reconstruction of the chest wall after balistic or other trauma requires good and
      muscle cover and creation of a new, stable and airtight wall. The authors present
      a case of balistic trauma of the right anterolateral chest wall which was
      urgently debrided and subsequently reconstructed by sandwich combination of a
      latissimus dorsi muscle flap and synthetic material composed of a sheet of PTFE
      and creation of two methylmethylacrylate ribs. The advantage of this technique is
      that it avoids the use of autologous tissue from an already weakened chest wall
      and confers a new chest stability in several sites corresponding to the wall
      defect with easily available and easy-to-use materials.

PMID- 8761065
TI  - [Reconstruction surgery after traumatic amputation of the thumb].
AB  - Reconstruction of the thumb after traumatic mutilation constitutes a delicate
      indication in order to select the technique most adapted to the patient's
      functional needs and esthetic desires. Pollicizations of healthy fingers are now
      used less frequently, except in the clinical context of very proximal
      amputations, but amputations of mutilated fingers remain a frequent indication.
      Progressive lengthening was associated with a high complication rate, although
      these complications have remained minimal. Osteoplastic reconstruction is still
      occasionally indicated in its modern version of composite flap. Finally, toe
      transfers now have a large place in young subjects, "tailored" transfer is
      preferred to first or second toe transfer in the case of isolated amputation of
      the thumb, due to its esthetic advantages.

PMID- 8761067
TI  - [Cancer of the gallbladder. A surgical experience. A propos of 143 cases].
AB  - The records of 143 patients with gallbladder carcinoma operatively treated
      between 1975 and 1995 were retrospectively reviewed. Abdominal pain was the most
      common symptom and was present in 103 patients (72%). Jaundice was present in 83
      patients (58%) and weight loss in 68 (47.5%). Pre-operative diagnosis was made in
      40.5% of the patients. Surgical procedures included cholecystectomy alone
      (16.8%), cholecystectomy with resection of the hepatic bed and lymphadenectomy
      (11%), cholecystectomy with biliary drainage (57.3%), and exploration with biopsy
      (14%). Surgery was considered as curative in 21.5% of the patients. Overall five
      year survival rate was 11%. Actuarial 5-year survival rate was 100%, 29% and 23%
      in patients with T1, T2 and T3 tumors. The five-year survival rate was nil in
      patients with T4 and T5 cancers.

PMID- 8761068
TI  - [Adenocarcinoma of the appendix. A propos of a case complicated by double local
      and parietal recurrence].
AB  - Adenocarcinoma of the appendix is rarely encountered and is usually discovered
      fortuitously at pathology examination of the surgical specimen. Six years after
      surgery for degenerative villous tumor of the appendix, local and parietal
      recurrence led to surgery in our patient. We present here the indications for
      complementary hemicolectomy and management of parietal scars resulting from the
      initial appendectomy.

PMID- 8761069
TI  - [Adenoma of Brunner's gland: a rare cause of duodenal obstruction].
AB  - Pseudo-tumoral hyperplasia of the Brunner glands is an exceptional
      dysembryoplastic or hyperplastic lesion which develops in the submucosa of the
      supra papillary proximal duodenum. We report a case of Brunner adenoma which led
      to duodenal obstruction. In 50% of the cases, the adenoma was asymptomatic but
      non-specific signs may lead to barium studies. CT scan of the abdomen or
      esogastroduodenal endoscopy which rarely provides formal histological proof.
      Major complications (hemorrhage, duodenal obstruction) and lack of formal
      diagnosis often leads to surgery, ideally with tumor resection after duodenotomy.
      Other prodecures (simple observation, endoscopic polypectomy,
      duodenopancreatectomy, biliary or digestive bypass without tumorectomy) may be
      entertained depending on the functional status, the volume of the tumor, presence
      of complications and overall general status.

PMID- 8761070
TI  - [Muscular metastasis of cancer of the pancreas. A propos of a case].
AB  - Metastasis to muscle is rare in cancer of the pancreas. We observed one case and
      reviewed the literature. The role of magnetic resonance imaging and the
      importance of echoguided needle biopsy for diagnosis is emphasized.

PMID- 8761071
TI  - [Significant value and therapeutic implications of routine gastroscopy before
      cholecystectomy].
AB  - Endoscopy of the upper digestive tract was performed in 338 consecutive patients
      undergoing cholecystectomy between January 1991 and December 1992. Pathological
      findings were seen in 160 (47.3%), 6.8% of the patients had peptic ulcers, 1.8%
      gastric erosions, 25.7% gastritis, 3.2% polyps, 4.7% hiatal hernias, 3.0%
      oesophagitis and 0.6% gastric cancer. In most patients the gastroscopic results
      did not correlate with the clinical symptoms. The therapy concept had to be
      changed in 8.3% of the patients due to gastroscopic findings, 23 patients with
      ulcers, 2 with erosions and 1 with oesophagitis had to be treated medically and
      so the cholecystectomy was postponed. Two patients with gastric cancer underwent
      gastrectomy. These results underline the importance of a routine gastroscopy
      before elective cholecystectomy.

PMID- 8761072
TI  - [Tumor implantation in cicatrization sites following surgery for digestive
      cancers].
AB  - The natural history of surgically treated intraabdominal malignancy is such that
      a large proportion of patients present tumor recurrence at wound sites. Numerous
      factors operating within the wound environment are important determinants in
      tumor cells arrest or growth at these sites. This article describes the
      interactions between the traumatized tissues and tumor cells, and attempts to
      understand the important factors that may have an impact on implantation of
      cancer cells in wound sites. Modifications of these biologic factors may
      represent new perspectives for preventing tumor recurrence in intraabdominal
      wound sites.

PMID- 8761073
TI  - [Treatment of rectal prolapse with elastic circling of the anus: Perspectives of
      utilization].
AB  - The Thiersch technique for treatment of rectal prolapsus has been largely
      abandoned because the metallic or non-resorbable wire is poorly tolerated and non
      extensible. Silastic can fulfil these requirements and was used in 11 patients,
      including two who underwent reoperations. Good results were obtained in 9. This
      technique is simple and can be proposed when the general status of the patient
      does not allow surgical cure of the prolapsus.

PMID- 8761074
TI  - [Adenoma of the choledochus].
AB  - Two patients with signs of an obstructed main bile duct underwent surgery.
      Choleductectomy was performed followed by Mirizzi exploration. Extemporaneous
      pathology examination of the intra-ductal tissue revealed benign adenoma of the
      main bile duct. Resection of the main bile duct with hepato-duodenal anastomosis
      was performed in the first patient and resection with end-to-end anastomosis in
      the second.

PMID- 8761075
TI  - [Gastric linitis plastica disclosed by diastatic perforation of the small
      bowell].

PMID- 8761076
TI  - [Rupture of the ileocecal valve following blunt abdominal trauma in a child].
AB  - The ileo-cecal valve was damaged by blunt abdominal trauma in a 5-year-old child.
      Subdiaphragmatic air led to operation. Cure was obtained with simple suture.

PMID- 8761077
TI  - [Anatomy and radio-anatomy of the intracranial venous system (dural sinuses
      excluded)].

PMID- 8761078
TI  - [Dural sinuses].

PMID- 8761079
TI  - [Superficial veins of the brain].

PMID- 8761080
TI  - [Deep venous system of the brain].

PMID- 8761082
TI  - [Pigmented erythroderma in AIDS. 5 cases].
AB  - INTRODUCTION: We report five cases of pigmented erythroderma occurring during
      AIDS, noteworthy for its unusual hyperpigmented feature, its advent at the
      terminal stages of AIDS, and an CD8 cells dermal infiltrate. PATIENTS AND
      METHODS: It is a retrospective study of five patients infected with HIV: a woman
      infected by transfusion and four homosexual men, average 55 years old. No one was
      intravenous drug user. They were all severely immunocompromised; HTLV I/II
      serology was negative. Skin biopsies were studied with light microscopy
      (Hematoxylin-eosin) and immunohistochemical studies were performed on frozen
      sections. RESULTS: The patients had an erythroderma of particular interest
      because of the associated hyperpigmentation, the severe repercussion (pruritus,
      weight loss), and the difficulty in treating (except systemic corticosteroids).
      The histology demonstrated a mononuclear dermal lymphocytic infiltrate, without
      epidermotropism and atypical cytonuclear feature. The phenotype of the infiltrate
      was uniformly of the suppressor-cytotoxic subset (CD8+, CD4-). COMMENTS: Our
      cases are like those previously described as "Pseudo-Sezary", mimicking a
      lymphoma during AIDS. Numerous factors are probably the cause of this
      hyperpigmented erythroderma: HIV, CD8 cells... CONCLUSIONS: This severe skin
      disease, complicating AIDS, seems very particular, but not yet clearly defined.
      In practice, the problem remains the treatment of this severe erythroderma,
      because only the systemic corticosteroids are effective, but this is debatable
      during the treatment of AIDS.

PMID- 8761083
TI  - [Hyperimmunoglobulinemia D or periodic fever syndrome. Cutaneous manifestations
      in 3 cases].
AB  - INTRODUCTION: We describe 3 cases of hyperimmunoglobulinemia D syndrome (hyper
      IgD syndrome). CASES REPORT: As the 2 first cases are conventional with an onset
      in childhood, the third one appeared later suggesting possibility of acquired
      syndrome. The 3 cases presented with one or several skin eruptions during febrile
      attacks. COMMENTS: Up to now, 64 cases of this syndrome have been described. Skin
      lesions are observed in 80 p. 100 of patients. In this particular clinical
      context, they must lead to the diagnosis. This 3 cases and the review of
      literature show that skin manifestations are polymorphic, transient, not very
      symptomatic and not correlated to IgD rates. Histological examination may reveal
      urticarial reaction with leucocytoclasic vasculitis, where IgD could directly or
      not interact.

PMID- 8761081
TI  - [Xeroderma pigmentosum. A study in 40 Algerian patients].
AB  - INTRODUCTION: Xeroderma pigmentosum (XP) is a rate autosomal recessive disorder
      related to DNA repair defects. Recently, modifications of oncogenes and mutations
      of the p53 suppressor gene have been reported in skin tumors of XP patients. The
      purpose is to study, through a series of 40 patients admitted to the Dermatologic
      Clinic of Algiers, the characteristics of XP in Algeria. PATIENTS AND METHODS:
      For each patient, familiarity, clinical and biological examinations and
      therapeutic results were studied. Biological studies have been axed mainly on
      analysis of DNA extracted from skin tumors of 18 patients to detect oncogene
      modifications by Southern blot and hybridization. A technic, based on single
      strand DNA conformation polymorphism (SSCP), has been carried out to detect
      rapidly mutations on the p53 gene. RESULTS: A consanguinity in the first degree
      is noted in 95 p. 100 of cases and a familiarity in 63 p. 100 of cases. The
      median age of patients is 10 years; sex ratio is close to one; 32 patients (80 p.
      100) are classic XP and 8 (20 p. 100) are XP variant. In 18 tumors analysed, the
      Ha-ras gene is amplified and/or modified in 50 p. 100 of cases. Only 3 tumors
      (16.6 p. 100) show mutations of the p53 gene (transitions C-T). Surgical
      treatment isolated or associated to polychemotherapy permitted to resolve tumors
      in 75 p. 100 of cases. DISCUSSION: In Algeria, XP are mainly classic with a
      particularly high frequency of occular (62 p. 100) and neurological
      manifestations (62 p. 100). Genetic studies confirm modifications of the Haras
      gene in direct relation with unrepaired UV lesions in classic XP and mutations of
      the p53 tumor suppressor gene characteristic of mutation spectra induced by UV.
      Surgery is the treatment of choice for tumors; polychemotherapy is an alternative
      in advanced cases.

PMID- 8761084
TI  - [A new allergen dibromodicyanobutane. Report of a study in 310 patients January
      December 1994].
AB  - INTRODUCTION: Methylisothiazolinone chloride (Kathon CG) and its derivatives,
      used as preservatives in cosmetics, have been shown to be allergenic when used in
      humans although preliminary studies in Guinea pigs failed to reveal any
      sensitization. Dibromodicyanobutane, associated with phenoxyethanol in Euxyl
      K400, has been proposed to replace the isothiazolinone derivatives in cosmetics.
      Preliminary study has shown that these thiazolinone derivatives are not
      allergenic in Euxyl K400. The similarity of these situations led us to
      hypothesize that dibromodicyanobutane could become allergenic. METHODS: We tested
      0.1 p. 100 dibromodicyanobutane in vaseline in the additional battery of the
      ICDRG battery in patients with contact eczema. Among the 310 patients tested,
      1.94 p. 100 had a positive test for this allergen (during this same period, 1.29
      p. 100 of the patients were positive for isothiazolinones). Three patients were
      hospitalized because of generalized eczema and 1 patient had changed occupation
      with no effect because the crems containing the allergen had not been avoided.
      CONCLUSION: Dibromodicyanobutane is a new allergen. Numerous cases of allergy
      have developed as use of the product becomes more widespread. The consequences of
      this sensitization may have an economic impact. Animal experimentation has been
      unable to predict this allergenic effect. Cosmetic products must be precisely
      labeled with a single international term for each specific molecule and the name
      of the preservative added to the active substance.

PMID- 8761085
TI  - [Melkersson-Rosenthal syndrome. Value of reduction cheiloplasty].
AB  - INTRODUCTION: The interest of cheiloplasty is not precisely defined in the
      treatment of Melkersson-Rosenthal syndrome (MRS). OBSERVATION: The case of a 32
      year-old woman, suffering from a typical MRS is reported. The lack of efficacy of
      various classical molecules (corticoseroids, hydroxychloroquine, dapsone,
      colchicine, clofazimine) led to a surgical therapy, consisting in cheiloplasty.
      Systemic corticosteroids were associated. The result was good, with a follow-up
      of 2 years. COMMENTS: Cheiloplasty is essentially of cosmetical interest, in the
      MRS, once the inflammatory process has been stopped (almost one year). Medical
      treatment (corticosteroids), is to be continued after surgery, to avoid
      recurrence.

PMID- 8761086
TI  - [Agranulocytosis induced by dapsone prescribed for dermatitis herpetiformis].
AB  - INTRODUCTION: Dapsone is a drug widely prescribed in dermatology. It can lead to
      undesirable side effects including hematologic disorders. CASE REPORT: A patient
      with dermatitis herpetiformis was treated with dapsone. Agranulocytosis developed
      6 weeks later and was revealed by fever and pneumonia which resolved under
      antibiotics. The agranulocytosis regressed without specific treatment after drug
      withdrawal. Blood counts returned to normal 2 weeks later. DISCUSSION: Dapsone
      induced agranulocytosis is in common (1/10,000 to 1/20,000). The drug is widely
      prescribed, particularly for leprosy. Nevertheless, when dapsone is prescribed
      for dermatitis herpetiformis, the risk of agranulocytosis increases 25-fold
      reaching 1/400. The indication for dapsone must always made carefully, with
      surveillance of the blood counts every 15 days during the first 3 months of
      treatment for dermatitis herpetiformis.

PMID- 8761087
TI  - [Blaschkolinear eruption with biological signs of lupus].
AB  - INTRODUCTION: Acquired inflammatory dermatoses of the adult with a blaschkolinear
      arrangement are rare. Their cause is unknown. CASE REPORT: We report the case of
      a 35-year-old man who presented an unilateral skin eruption covering the forearm
      and with secondary blaschkolinear extension to the arm, the axillary region and
      the chest. In this particular case, the patient was positive for RNP type anti
      nuclear antibodies and direct immunofluorescence was positive in both biopsies of
      the lesions and of healthy skin. The eruption lasted 6 months and regressed
      spontaneously. DISCUSSION: Such cases are exceptional and the nosology is
      difficult to establish. A particular form of lupus erythematosus? Fortuitous
      coexpression of lupus antibodies and blaschkitis in an adult?

PMID- 8761088
TI  - [Neonatal cutaneous hematopoiesis disclosing congenital rubella].
AB  - INTRODUCTION: Congenital rubella, which should disappear with widespread
      vaccination and mandatory obstetrical care, can occur as a purpuric eruption in
      the newborn. We report a case of blueberry muffin baby. CASE REPORT: An infant
      delivered after an "uneventful" pregnancy presented a generalized "purpuric"
      eruption and had axial hypotonia. Histology of a biopsy showed evidence of
      cutaneous erythropoiesis. The complete workup led to the diagnosis of congenital
      rubella. DISCUSSION: Cutaneous erythropoiesis is a well defined clinical and
      histological entity. There are several causes including infection and hematology
      disorders. Metastasis of a neuroblastoma, which must be eliminated by early
      biopsy, is the main differential diagnosis. CONCLUSION: Blueberry muffin rash is
      never idiopathic. The prognosis depends on the cause. Physicians should remember
      that congenital rubella has not yet been completely eradicated in France.

PMID- 8761089
TI  - [Comparative epidemiology of pemphigus in Tunisia and France. Incidence of
      foliaceus pemphigus in young Tunisian women].
AB  - INTRODUCTION: Recent studies have suggested that pemphigus foliaceus is quite
      frequent in young Tunisian women. In order to confirm this hypothesis, we
      compared the incidence of pemphigus in general in Tunisia with that in the Ile-de
      France region. METHOD: All new cases of pemphigus diagnosed during a 6-year
      period were reviewed in our dermatology and pathology laboratories. These cases
      were classed as pemphigus foliaceus or pemphigus vulgaris on the basis of
      histology reports. RESULTS: In France, the incidence was 1-7 new cases per
      million per year (95 p. 100 confidence interval 1.4-2.1). Pemphigus vulgaris was
      diagnosed in 73 p. 100 of the cases with an incidence increasing with age. Sex
      ratio (F/M) was 1.2. The incidence observed in Tunisia was significantly higher
      than that observed in France with 6.7 new cases per million per year (95 p. 100
      confidence interval 5.8-7.7). Pemphigus foliaceus was more frequent (61 p. 100),
      the sex ratio (F/M) was 4.1. Incidence was higher in young women, with 20 new
      cases of pemphigus foliaceus per million per year among women from 25 to 34 years
      of age. These levels were higher in rural desert areas. No familial cases were
      observed and only one case occurred in a child. DISCUSSION: These findings
      confirm the specific epidemiology of pemphigus in Tunisia, which appears to be
      similar and also different from that in Brazilian pemphigus. As in Brazil, there
      was a predominance of pemphigus foliaceus in young adults living in rural areas
      in poor socioeconomic conditions. However in Tunisia the disease predominates
      significantly in women and there are no familial and rare juvenile cases.

PMID- 8761090
TI  - [Antiseptics in skin diseases].

PMID- 8761091
TI  - [Management of male urethritis].

PMID- 8761092
TI  - [Venous ulcer. Dermatosurgical and surgical approach].

PMID- 8761093
TI  - [Monthly question. Are systematic pathological tests mandatory?].

PMID- 8761094
TI  - [Repair of articular cartilage with biological tissues. An experimental study in
      sheep].
AB  - The purpose of this study was to assess the joint cartilage's capacity for repair
      and the potential of various biological tissues as replacements for damaged
      cartilage. METHODS: We operated 30.3 months old, lambs, creating a chondral
      lesion which was left untreated in group I and treated with a fresh chondral
      implant in group III, a frozen chondral implant in group IV, and a frozen
      periostal implant in group V; in group II the lesion extended as far as the
      subchondral bone. The lesions were performed in the loading area of the medial
      condyle of the knee. Follow-up time was 6 months, and the results were assessed
      histologically. RESULTS: In the chondral lesions which remained untreated (group
      I), degeneration of the exposed layers occurred, and loss of both cartilage
      thickness and homogeneity of the matrix was noted. Where the lesion extended as
      far as the subchondral bone (group II), repair was found to have taken place with
      a fibrous tissue indistinguishable from cartilage. When cartilage was implanted
      (group III and IV), the integration of the implant depended on wether there was
      any contact between the implant and the surrounding tissue. DISCUSSION: The
      integrity of the fresh implants was maintained better than that of the frozen
      ones, which were found to contain cells with a proliferative capacity. When
      periosteum was placed over the chondral lesion, we observed the formation of a
      very loose fibrous tissue in which the initial stages of differentiation could be
      appreciated in the deepest layers.

PMID- 8761095
TI  - [Guepar's total radio-carpal prosthesis in the surgery of the rheumatoid wrist.
      Apropos of 72 cases reviewed].
AB  - PURPOSE OF THE STUDY: Total wrist arthroplasty is an alternative to arthrodesis
      in the treatment of the rheumatoid wrist. MATERIAL AND METHODS: Seventy-two
      GUEPAR total wrist arthroplasties in sixty-four patients with rheumatoid
      arthritis were reviewed 1 to 10 years after the operation (average follow-up of 4
      years). GUEPAR total wrist arthroplasty is a bicondylar prosthesis. The radial
      component made of polyethylene is cemented in the radius. The carpal component
      made of metal is fixed by two screws in the second and the third metacarpal. This
      component is constitued by two pieces: a perforated lower part permitting the
      passage of the screws and its metacarpal fixation and a biconvex cover fixed on
      the lower part by a micro-screw. RESULTS: In preoperative evaluation, all
      patients had severe pain and loss of function. Post-operatively, 89 per cent had
      no pain or mild pain and 96 per cent had better function. The average arc of
      flexion-extension was 47 degrees preoperatively and 39 degrees postoperatively.
      There were no deep infections or dislocations. Seventy percent of the patients
      were satisfied but eleven wrists (15 per cent) required revision: 5 cases for
      prosthesis revision and 6 cases for implant removal and arthrodesis. Prosthesis
      revisions were justified by the unscrewing of the carpal component micro-screw:
      they gived good results. Arthrodesis was required for 4 radial component
      loosening and for 2 important bone resorptions under the carpal component. Radial
      component loosening was associated in 3 cases with unscrewing of the micro-screw.
      Radiographical analysis showed in nearly all cases of this serie a bone
      resorption under the carpal component. This resorption was 2 mm wide at an
      average of to 2 years and 4 mm wide at 4 years. DISCUSSION: Clinical results of
      this study are good but eleven wrists required revision. Nine of these revisions
      were due to anomalies of first prosthesis: the unscrewing of the carpal component
      micro-screw was accountable to abnormal use of polyethylene with reaction of the
      wear products and loosening of the radial component. This problem is now
      resolved. More disquieting is the bone resorption under the carpal component. In
      fact, this resorption was constant and evolutive. It was very likely due to micro
      movements between the metacarpal screws and the carpal lower part. Also, the
      conception of the metacarpal-fixation of this prosthesis must be revised.
      CONCLUSION: In rheumatoid arthritis, wrist arthrodesis gives good results if
      nothings affects the fingers, elbow or shoulder. If they are affected, total
      wrist arthroplasty is an alternative. Long term loosening of total wrist
      arthroplasty is a significant problem so its indication must be reserved for old
      patients.

PMID- 8761096
TI  - [Acetabular implant in Charnley's total arthroplasty. Review of 309 cases with a
      minimum of 15 years follow-up].
AB  - PURPOSE OF THE STUDY: The aim of this study was to appreciate the long term
      result of 309 acetabular components of total hip arthroplasty. MATERIALS AND
      METHODS: All were performed using Charnley's prosthesis and cement, by one
      surgeon, between January 1972 and December 1975. Clinical function was graded
      according to Postel-Merle-d' Aubigne's scoring system (PMA score). We measured
      wear of polythylene using a personal method, on anteroposterior radiographs of
      the pelvis. Radiolucent line were appreciated by Delee and Charnley's criteria,
      migration by Massin's criteria. Survivorship curves were calculated with
      radiolucent lines, as migration, on 15 years. We compared the effect of different
      parameters on wear and loosening of the sockets. RESULTS: At 15 years follow-up,
      we found 51.5 per cent hips with the highest PMA score (18). Revision for socket
      loosening was 3.88 per cent, the same for dislocations. Concerning 25 per cent of
      the sockets, wear of polyethylene was evaluated less than 0.065 mm a year,
      concerning 50 per cent of them, it was evaluated less than 0.11 mm a year, at
      last concerning 75 per cent of them, it was evaluated less than 0.16 mm a year.
      No significant correlation was established between the tilt of the acetabular
      component and the wear of polyethylene. We observed no radiolucent lines for 60
      per cent of the implants, nor migration for 83 per cent of them. Statistical
      analysis proved the influence of the wear on radiolucent lines and migration.
      DISCUSSION AND CONCLUSION: The analysis confirms a moderate wear of polyethylene
      during 15 years. We introduce an original method for its measurement and its
      formulation. This method allows a truly description of wear in long term results.
      This analysis confirms also that several parameters intercede on loosening; these
      are different if one considers radiolucent lines or migration. We do think at
      last, that the best positionning of the socket in the A.P. view should approach
      35 degrees.

PMID- 8761097
TI  - [Treatment of pseudarthrosis of the clavicle by bone plate with screw fixation
      and autologous spongiosa graft].
AB  - PURPOSE OF THE STUDY: The authors review and evaluate the operative treatment of
      mid-shaft clavicular non-union by compression plate osteosynthesis and most
      frequently by decortication and autogenous bone grafting. MATERIAL AND METHODS:
      From 1979 to 1990, 11 consecutive patients, 9 males and 2 females, mean age 33.5
      years, with symptomatic non-union of mid-shaft clavicular fracture were operated
      and followed-up for an average of 4 years. The pseudarthrosis was atrophic in 10
      and hypertrophic in 1 patient. The initial treatment of the fracture was always
      conservative. RESULTS: All patients achieved bone union by 3-7 months post
      operatively. The functional results were excellent in 9 patients. The remaining
      two patients had mild symptoms such as occasional pain related to weather,
      soreness of the muscles with overhead lifting and discomfort of the shoulder.
      Minor complications were noted such as 1 delayed wound healing, 3 cheloid scars
      and 1 transient partial paresis of the brachial plexus. DISCUSSION: Symptomatic
      non-union of the mid-shaft clavicular is a rare complication, mainly after non
      operative treatment (11 cases in 12 years in our series). Factors responsible for
      non-union are the initial high velocity injury, the cominution, the overlapping
      and great displacement, the paucity of cancellous bone at this site and the
      trapezius interposition. Internal fixation by compression plating, decortication
      and bone grafting in atrophic non-union often encountered is a safe reliable
      method allowing uncomplicated healing and acceptable functional results.

PMID- 8761098
TI  - [Contralateral preventive screwing in proximal femoral epiphysiolysis].
AB  - PURPOSE: The incidence of bilaterality in slipped capital femoral epiphysis
      (SCFE) ranges, in the literature, from 19 per cent to 80 per cent. The role of
      contralateral pinning is to prevent late slipping of the femoral epiphysis and
      its complications. The purpose of this study is to assess the usefulness of
      routine preventive contralateral pinning in SCFE, and to evaluate its
      complications. MATERIAL AND METHODS: We reviewed retrospectively 74 consecutive
      patients treated for unilateral SCFE by associated routine preventive
      contralateral pinning. The age at surgery ranged from 10 years and 6 months to 16
      years and 10 months. The osteosynthesis was achieved by a single cannulated
      holothreaded screw with a cross grooved head, with or without the use of washers.
      RESULTS: An accidental pin penetration was noted in 4 cases. The epiphyseal
      position of the screw was satisfactory in 56 cases. The patient was allowed to
      walk the second or third day after surgery with the use of crutches. All our
      patients were reviewed after the end of squeletal growth. The follow-up ranged
      from 2 to 12 years and 8 months. The age at which the patient was last seen
      ranged from 15 years and 7 months to 27 years. Two major complications were
      noted: a femoral fracture at the level of the screw penetration in one case, and
      secondary slipping of the epiphysis after premature removal of the screw in two
      cases. The removal of the screw was considered to be very difficult in 10 cases.
      A relative overgrowth of the greater trochanter was noted in 8 cases, and was of
      no clinical significance. No infection was noted. At last follow-up, the shape of
      the femoral head and the function of the hip were normal in all cases except for
      one hip where severe coxa vara developed because of a secondary slip after
      premature removal of the screw. DISCUSSION: There is a lot of controversy about
      the real necessity of routine preventive contralateral osteosynthesis in SCFE. In
      our experience this surgery succeeded in reducing the incidence of secondary
      contralateral slipping. The two cases in our series could have been prevented by
      an accurate timing of screw removal. The complications of this procedure are
      rare, and it could be done during the same operative time as the SCFE side's. The
      only case of femoral fracture was secondary to a violent car accident.
      CONCLUSION: The routine prophylactic controlateral osteosyntheis in SCFE, using a
      single screw is a safe procedure and allows to reduce the incidence of
      bilaterality.

PMID- 8761099
TI  - [Secondary internal osteosynthesis after external fixation for recent or old open
      fracture of the lower limb].
AB  - PURPOSE: The purpose of our study is to analyse the indications, results and
      limits of secondary internal fixation after external fixation for open fracture
      of the lower limb. MATERIAL: Our series covered 21 patients treated between 1991
      and 1994. There were 17 men and 4 women. Tibia was affected 17 times and femur 5
      times (one bifocal fracture). In Gustilo's classification, we had 1 case of type
      1, 12 of type II and 8 of type III. METHODS: We used 15 times the FESSA External
      Fixator and 6 times a monotube external fixator in emergency. We have done
      secondary 11 intra medullary nailing and 11 patients were treated by plating (one
      patient had both) 13 patients had a bone graft (cortico-cancellous graft). In the
      first group of patients (10 cases), the initial treatment gave us good results
      for both skin and bone healing. The external fixation was replaced by an internal
      one in order to accelerate bone consolidation and to allow an early weight
      bearing. Removal of the external fixation was made at an average of 4 months
      postoperative. In the Second group (11 cases) the internal fixation was proposed
      because of an insufficiency of the external fixation leading to complications as:
      non union, mal union and bone defects. External fixation was removed in a mean
      time of 8 months. Internal fixation was completed by local bone autograft.
      RESULTS: 17 patients have been reviewed. Consolidation occurred with an average
      of 6 months after internal fixation 1 to 24 months. We had no deep infection but
      only 2 superficial ones. DISCUSSION: We chose 2 types of indication, and we
      called them programmed and for necessity. The first group of 10 patients whose
      stain was moderate and whose initial setting up had permitted a perfect anatomic
      reduction with a rapid wound healing. Internal fixation was performed after a
      short duration of external fixator. An early weight bearing was allowed so that
      the functional recovery could be obtained quickly. The second group is
      represented by patients whose internal fixation was done for non union, malunion
      or bone defect. In such a case autogenous cancellous graft was used to fill the
      defect.

PMID- 8761100
TI  - [Fractures of the tarsal scaphoid].
AB  - PURPOSE OF THE STUDY: The authors relate a series of 47 cases of tarsal scaphoid
      fractures, between 1976 and 1992. MATERIAL AND METHODS: These fractures occurred
      11 times after a high level fall, 28 times after a motor vehicle accident and 8
      times after a direct traumatism. The fracture line was vertical 35 times;
      horizontal 27 times. An impaction was often associated (32 cases). In 17
      observations, a true enucleation occurred as a part of the fracture dislocation.
      Many periscaphoidal lesional associations were found. 39 fractures were fixed.
      Radiographs showed 30 consolidations with an anatomical reduction. 37 patients
      were reviewed with an average follow up of 7 years and 6 months. RESULTS: Results
      were assessed using Mestagh's scoring system: 7 very good, 15 good, 6 fair and 9
      bad. The very good and good results represent 59 per cent. In 37 patients
      reviewed, the clinical investigation showed 8 deformities of valgus flat foot, a
      varus foot, requiring 11 times orthopedic soles wearing. 11 patients had a
      lameness. Radiological results showed 11 times a peri-scaphoidal arthrosis, a
      necrosis and 2 non union. A narrowing of the astragalo-cuneate joint line was
      found 8 times. DISCUSSION: Various anatomical types don't have the same
      prognosis. Vertical and horizontal fractures gave 18 times a very good and good
      result when in 11 reviewed patients with a fracture dislocation, we noticed 7
      poor or bad result. An osteosynthesis by screw gives goods results when fragments
      are large. For compound fracture when a surgical procedure will be insufficient,
      the conservative treatment, if keeps a sufficient breadth of medial arch, can
      give a satisfactory result. An immediate astragalo-scaphoidal arthrodesis can be
      suggested in front of a multi-fragmentary dislocation fracture. CONCLUSION: The
      scaphoidal tarsal fracture is unusual and its diagnosis remains sometimes
      difficult. The treatment is often surgical by direct approach. In consideration
      of the pejorative post-operative outcome of fracture dislocations, some authors
      suggest an immediate astragalo-scapho-cuneate arthrodesis.

PMID- 8761101
TI  - [The foot in hereditary motor and sensory neuropathies in children].
AB  - PURPOSE: Although Charcot-Marie-Tooth disease (CMT) is known to be the most
      common neuromuscular cause of pes cavovarus, other paralytic deformities of the
      foot may be present with hereditary motor and sensory neuropathies (HMSN). The
      purpose of our review is to analyze these foot deformities and to assess the
      results of the different therapeutic methods used. MATERIAL AND METHODS: We
      evaluated 66 patients who had HMSN and had a total of 127 foot deformities. Fifty
      three patients had CMT, 6 patients Dejerine Sottas disease (DS), and 7 patients
      had an unclassified HMSN. The average age at diagnosis was of 9 years and 11
      months. There were 35 males and 31 females. The deformity was unilateral in 5
      cases. In 50 bilateral cases, the severity of the deformity was not similar in
      both feet. In three bilateral cases, the deformity was completely asymmetrical.
      The chief complaint was mainly deformity in all cases, followed by subtalar or
      ankle instability in 57 cases. There were 105 cases of cavus or cavovarus, and 22
      cases or valgus or planovalgus deformity (8 of which changed spontaneously to
      cavovarus). A non surgical treatment was undertaken in 57 cases for minor
      deformity. Soft tissue release with or without osteotomies was done in 39 cases,
      and triple arthrodesis in the remaining 31 cases. A clawtoe deformity was treated
      operatively in 14 cases. RESULTS: The mean follow-up period was 6 years and 9
      months for non operated feet and 7 years and 10 months for operated feet (all of
      the surgically treated feet were reviewed after the end of growth). Three
      patients of the non operated group and 8 patients of the surgically treated feet
      underwent triple arthrodesis for a recurrence of the deformity. Thirty nine per
      cent of the feet which underwent triple arthrodesis (a total of 42 feet) were
      considered to have fair or bad result at 6 years and 3 months follow-up period.
      DISCUSSION AND CONCLUSION: The foot deformity in HMSN is of a wide variety. A
      valgus flat foot is not uncommon, especially in DS and unclassified neuropathies.
      The young age of the patient is not a contrindication to surgical management.
      Even if minor previous surgeries do not always succeed in avoiding recurrence of
      the deformity, they nevertheless prepare the foot fort a possible triple
      arthrodesis, that will be done in better anatomical conditions.

PMID- 8761102
TI  - [A simple technique of removal of femoral cement plug in total hip prosthesis
      revision].
AB  - During replacement of loosened or painful cemented femoral prosthetic stem, the
      extraction of a large size distal cement plug is rarely an easy matter. To make
      it simple, quick and safe (no wide surgical exposure, no X-ray exposure) we
      propose a new technique based upon the perforation of the cement plug by a drill
      which crosses a jig inserted into the cavity where the femoral stem had been
      removed. Correctly used the procedure can help the surgeon to solve the difficult
      problem of removing the femoral cement plug and consequently it can allow the
      placement of a biomechanically ideal conventional length femoral component into a
      femur not weakened by a perforation, a fenestration or an osteotomy.

PMID- 8761103
TI  - [An original procedure for cement diaphyseal extraction. The segmental cement
      extraction system or SEG-CES].
AB  - PURPOSE OF THE STUDY: We report our first eleven uses of a new cement mantle
      extraction system. The basis of this technique relies on a cement bone interface
      with a lower strength compared to the old cement-new cement interface. MATERIAL
      AND METHODS: The first stage of the procedure consists in a specific preparation
      of the inner surface of the old cement, mantle. It should be clean and dry after
      being abraded with a stainless steel wire brush. Then a thin cement syringe
      filled with low Viscosity PMMA cement, is injected in the old mantle in a
      retrograde fashion. A threaded rod with nuts is centered within the cement sheath
      to the bottom and held until the injected cement has fully polymerised. Then the
      threaded rod is unscrewed from the femur; nuts are established along the entire
      length of the cement column. To prevent trochanteric fracture occurring upon
      cement extraction, its is important to clear away sufficient bone from the
      lateral aspect of the canal. A series of extraction rods are then used to
      sequentially remove the cement mantle. The removal rod is screwed back into the
      threaded channel at a distance of every one to three nuts, and then attached to
      the slap hammer via a quick release connection. Cement extraction is performed
      using deliberate slaps of the slap hammer. The last segment is drilled with the
      use of a distal plug drill centering sleeve. After having inserted the plug
      removal rod, the last segment is extracted. We used this technique eleven times
      in 8 hips for 5 loosening of femoral component and 3 revisions hip arthroplasties
      without loosening and 2 revisions knee arthroplasties without loosening (an
      extraction system for the femur and the tibia). RESULTS: For the 5 loosening
      cases extraction was easy. In 2 cases, cement mantle was removed as a single "en
      bloc" piece. In the 3 other cases, the extraction was segmental only in the
      distal third of the cement mantle. Without loosening, the extraction was
      completely segmental. In all cases, cement mantles were successfully removed.
      There was no fracture and no loss of bone stock. There was only one "fissuration"
      alpha the great trochanter and we only made one distal window. All hip
      arthroplasties were replaced and arthrodesis were performed after removal of the
      knee arthroplasties. DISCUSSION: The cement-assisted mantle removal technique
      appears to be a simple, quick and effective methods for cement mantle removal.
      Perforation and diaphyseal window can be avoided by the technique even when
      loosening does not exist. However, it is necessary to establish a thorough
      preoperating plan in order to eliminate contraindications such as too narrow or
      too curved sheath. CONCLUSION: It appears that this new procedure will facilitate
      future reoperations which are reputed to be difficult and dangerous.

PMID- 8761104
TI  - [Use of ultrasound for the removal of cement in hip prosthesis reoperations].
AB  - PURPOSE OF THE STUDY: One of the challenges facing the surgeon during revision
      procedures is the harduous task of complete acrylic cement removal while leaving
      the surrounding cortical bone intact. A set of ultra sonic driven instruments has
      been evaluated revisions of total hip and total knee prosthesis. The principle is
      to convert standard electrical energy into mechanical energy via an ultrasonic
      transducer. MATERIAL: 10 revisions of cemented hip prosthesis and one of a total
      knee prosthesis (Guepar Howmedica) have been performed with success easily and
      safely. RESULTS: The ultra-sonically driven tools used have reduced the incidence
      of perforation (1 cases), with no need to cut cortical windows to remove the
      distal plug, and have also reduced the time for cement removal and the intra
      operative blood loss. CONCLUSION: The author thinks that this technique provides
      a great facility in revision surgery. A larger study will be done soon.

PMID- 8761105
TI  - [Arthroscopy of the knee joint. Conclusions and recommendations].

PMID- 8761106
TI  - [Aortic valve replacement with pericardial bioprosthesis in patients under 60
      years of age. Experience over 10 years].
AB  - Between July 1984 and December 1993. 110 patients, younger than 60 years,
      underwent aortic valve replacement with a Carpentier-Edwards pericardial valve.
      75.5% were male, with a mean age of 49.6 years (range: 16 to 59 years). Mean
      clinical status was 2.25. Operative mortality was 0%. All patients but 3 were
      followed up with a total follow-up of 454 patient-years and an average of 4.8
      years. The 10-year actuarial survival is 91 +/- 6%. We observed 8 valve-related
      complications (1.7% patient-years): 3 cases of endocarditis, 3 structural
      failures, 1 thromboembolic event, and 1 perivalvular leak. 1 patient died from a
      valve-related cause, and 2 reoperations were necessary. The 8-year actuarial
      probability of absence of valve-related death is 99 +/- 1%, thromboembolism 98 +/
      2%, endocarditis 96 +/- 4%; reoperations 96 +/- 4%, and valve failure 97 +/- 3%.
      The 10-year valve-related complication rate is satisfactory, but the durability
      of the prosthesis in this group of young patients remains unknown. A longer
      follow-up is mandatory to draw definitive conclusions.

PMID- 8761107
TI  - [Long-term development of aortic valve stenosis surgically treated at an advanced
      stage].
AB  - From January 1972 to June 1990, 112 patients (39 to 83 years old), 67 males and
      45 females were submitted to surgery for sever calcified aortic stenosis. 68
      patients were in NYHA III (60.72%) and 44 in NYHA IV. Early mortality included 8
      patients (7.14%), 6 died for cardiac reasons. Late mortality was 27.67%.
      Actuarial survival rate (including postoperative mortality) was 88.39%, 77.67%,
      67.85% and 65.17% at one year, five, ten and fifteen years, respectively. Results
      were significantly correlated to left branch block on preoperative EKG, episodes
      of complete heart failure, significant coronary stenosis, the cardioplegia
      technique and the association with coronary bypass.

PMID- 8761108
TI  - [Surgical management of ventricular arrhythmia after myocardial infarction].
AB  - From December 1986 to December 1994, 36 patients underwent surgical treatments
      for intractable ventricular tachyarrhythmias after myocardial infarction.
      Preoperative electrophysiological studies confirmed inducibility of sustained
      monomorphic ventricular tachycardia and its resistance to antiarrhythmic drugs in
      all patients, 2 different concepts were assessed: 1) 22 non-guided surgical
      procedures were performed. 17 patients underwent Encircling thermic exclusion by
      Nd-Yag laser beam (Group A) and 5 patients underwent extended cryoablations (n =
      5) with endocardial resections. Mean preoperative value of left ventricular
      function in Groups A and B were 35.23% and 30.20% respectively. 10 coronary
      bypasses (Group A: n = 8; Group B: n = 2) and 1 mitral valve replacement (Group
      A) were also performed. Perioperative mortality was 5.5% in Group A. No
      perioperative deaths occurred in Group B. Ventricular tachycardias recurred
      spontaneously in 2 patients (Group A) and 7 remained inducible after evaluation
      by electrophysiological studies. 2) 14 patients underwent extended cryoablations
      guided by intraoperative cardiac mapping, including endocardial resections in all
      cases. Mean preoperative value of left ventricular function was 32.80%. Mitral
      valve replacements were achieved in 2 cases, 1 perioperative death occurred
      (7.14%). Clinical recurrence of ventricular tachycardias concerned 1 patient
      (7.69%) and 2 remained inducible after electrophysiological studies (15.38%). We
      conclude that the better results obtained with cardiac mapping and cryoablations
      may be due to available detection and destruction of deep septal arrhythmogenic
      substrates. Moreover, cryoablation creates a nonarrhythmogenic scar and can be
      performed in papillary muscles while preserving the structure of the tissue. No
      postoperative alteration of left ventricular function was therefore observed.

PMID- 8761109
TI  - [A study of the 30 minutes following reperfusion after crystalloid and cold blood
      cardioplegia by enzymatic and metabolic analysis of coronary blood flow].
AB  - Post-ischemic reperfusion phenomena were studied in two methods of myocardial
      protection: crystalloid cardioplegia (St Thomas n(o) 2) and cold blood
      cardioplegia (Buckherg) during cardiopulmonary bypass for human myocardial
      revascularisation. Myocardial protection was assessed on the course of
      hemodynamic parameters, reperfusion arrhythmias and biochemical analysis of the
      coronary flow after cross-clamp removal: creatine phosphokinase (CPK-MB) and
      nucleotide adenine metabolites (adenosine, inosine, hypoxanthine, xanthine and
      uric acid). The study was performed in two groups of 14 patients. Hemodynamic
      conditions were similar in both groups during reperfusion in order to avoid
      different coronary flow. Under these conditions, myocardial protection by cold
      blood cardioplegia reduced reperfusion arrhythmias, and resulted in a loss of CPK
      MB release. Furthermore, cold blood cardioplegia provided protection of
      myocardial energy metabolism by reducing the loss of metabolites, purine bases
      and oxypurine bases into the coronary sinus. Our results also show that
      hypoxanthine is probably the final product of ATP degradation in human myocardial
      tissue.

PMID- 8761110
TI  - [Constrictive pericarditis after cardiac surgery].
AB  - Constrictive pericarditis is a rare complication of cardiac surgery. Among 7851
      patients who underwent cardiac surgery at Nantes University Hospital,
      postoperative constrictive pericarditis was diagnosed in 5 patients: 0.63%. All
      patients were men aged 49 to 77 years (mean 62.5) Four patients underwent
      coronary artery bypass graft surgery and one patient required mitral and aortic
      valve replacement. The mean time to onset of symptoms after the first operation
      was 21 months. The main clinical symptom was right ventricular failure. In all
      patients, the diagnosis was established by right catheterization which showed
      diastolic dip-plateau. A radical pericardectomy was performed in all but one of
      the patients, who was treated medically. Clinical signs resolved in all five
      patients. The diagnosis of constriction after cardiac-surgery is not easy, as the
      symptoms are non-specific. A symptomatic patient believed to have myocardial
      failure after cardiac-surgery could therefore actually instead have occult
      constriction.

PMID- 8761111
TI  - [A rare complication of mediastinitis: rupture of the right ventricle].
AB  - Two cases of right ventricular free wall rupture secondary to mediastinitis after
      cardiac surgery are reported. This complication is unusual and characterized by
      the singular mechanism of rupture (traction involving right ventricular free wall
      and chest adhesion) which occurs during episodes of coughing. Treatment by
      omentoplasty en sureda favorable outcome in both cases.

PMID- 8761112
TI  - [False empyema after artificial pneumothorax. An original entity: type B non
      Hodgkin malignant lymphoma].
AB  - Malignant lymphoma developing in the lung after therapeutic pneumothorax is a
      rare condition in Europe. The authors report one case admitted after a 40-year
      history of pyothorax resulting from artificial pneumothorax for treatment of
      pulmonary tuberculosis. The diagnosis at admission was an infection of the
      chronic pyothorax associated with a lung mass. Histology confirmed the presence
      of non-hodgkin lymphoma B in the lung mass associated with Epstein-Barr virus.
      After surgery, chimiotherapy was not effective. Diagnosis before surgery could
      optimize the medical management. The long-term outcome is pejorative in most
      cases.

PMID- 8761113
TI  - [Cystic form of extralobar pulmonary sequestration. A propos of a case].
AB  - Case of bronchogenic cyst associated with extralobar pulmonary sequestration is
      presented in a 10-month-old baby. At thoracotomy, the tumor was an extralobar
      pulmonary sequestration with a central cyst surrounded by two pulmonary lobes
      vascularised by systemic vessels. Resection was easy. The cyst had a respiratory
      mucosa and was benign. The pathogenesis of the malformation is discussed.

PMID- 8761115
TI  - [Hereditary non-polyposis colorectal cancer: genetic diagnosis].

PMID- 8761114
TI  - [Diagnosing predisposition to tumor development by genetic typing].

PMID- 8761116
TI  - [Management of a family with genetic hemochromatosis].

PMID- 8761117
TI  - [Genetics of Crohn disease: a complex model].

PMID- 8761118
TI  - [Physiopathological and diagnostic value of genetic changes in digestive
      cancers].

PMID- 8761119
TI  - [Prognostic value of genetic changes in colorectal cancers].

PMID- 8761120
TI  - [Food allergy].

PMID- 8761121
TI  - [Characteristics of celiac disease in children].

PMID- 8761122
TI  - [Treatment of Crohn disease in children].

PMID- 8761123
TI  - [Constipation in children: from symptoms of Hirschsprung disease to chronic
      intestinal pseudo-obstruction syndromes].

PMID- 8761124
TI  - [Viral hepatitis in children].

PMID- 8761125
TI  - [Pancreatitis in children].

PMID- 8761126
TI  - [Use of 5-fluorouracil in digestive cancer].

PMID- 8761127
TI  - [From Barrett esophagus to adenocarcinoma: can the dangers of natural history be
      overcome?].

PMID- 8761128
TI  - [Management of a patient with cancer of the cardia].

PMID- 8761130
TI  - [Management of a patient with gastric lymphoma].

PMID- 8761129
TI  - [Gastric lymphoma: natural history and classification].

PMID- 8761131
TI  - [Management of disclosed hepatic metastases].

PMID- 8761132
TI  - [What is the usefulness of enteroscopy?].

PMID- 8761133
TI  - [When is magnetic resonance imaging of liver diseases required?].

PMID- 8761134
TI  - [What can be expected from x-ray computed tomography in gastrointestinal
      diseases?].

PMID- 8761135
TI  - [Biliary and esophageal self-expandable stents].

PMID- 8761136
TI  - [Endoscopic diagnosis and treatment of flat colorectal neoplastic lesions].

PMID- 8761137
TI  - [Gastroenterology: a threatened occupation?].

PMID- 8761138
TI  - [Low-dose polyethylene glycol 4000: digestive effects. Randomized double-blind
      study in healthy subjects].
AB  - OBJECTIVES: It was recently demonstrated that low-dose polyethylene glycol 4000
      (PEG) electrolyte lavage solution, a colonic lavage solution used for cleaning
      the gut before colonic procedures, is effective in the treatment of chronic
      constipation. The aim of our study was to determine the digestive effects of low
      dose PEG 4000 without electrolyte addition in healthy subjects. METHODS: Sixteen
      healthy male subjects with normal transit were included in a randomized
      controlled cross-over study. Study design included 4 successive periods: pre
      inclusion (12 days), treatment (7 days), wash out (7 days), treatment (7 days).
      Colorectal transit time measurement and stool collection for physical and
      chemical investigations were performed during each period. During treatment
      period, either 20 g/d of PEG without electrolyte addition or placebo was given to
      each subject. RESULTS: With PEG, stool frequency increased significantly (1.26 +/
      0.09 with PEG versus 1.07 +/- 0.09 with placebo; P < 0.05) but no significant
      change in consistency was observed (P = 0.07). Total and segmental colonic
      transit time were comparable with PEG and placebo. Mean stool weight increased
      from 74 g/d, by increase of stool water output (54 g/d) and dry stool weight (20
      g/d). Increase of stool water output was not associated with improvement in stool
      hydration: stool water content was comparable with PEG (75.4%) and with placebo
      (75.6%). No change was observed for the following parameters: stool electrolytes
      output, pH, organic acids, fecal output of fat, alpha-1-antitrypsin clearance,
      presence of red and white blood cells. Fecal output of protein increased
      significantly from 3.2 +/- 0.4 g/d to 6.0 +/- 0.7 g/d (P < 0.05). CONCLUSION: No
      effect on colonic transit and on stool hydration was observed with low dose of
      PEG 4000. With 20 g/d of PEG 4000, electrolytes addition is not necessary.

PMID- 8761139
TI  - [Measurement of fecal elastase 1 by immunoreactivity: a new indirect test of the
      pancreatic function].
AB  - AIM: The aim of this study was to evaluate the potential and precision of the
      fecal elastase type 1 rest in comparison to the secretin-pancreozymin-test in the
      diagnosis of exocrine pancreatic insufficiency. METHODS: We studied 254 stool
      samples from 102 individuals without malabsorption (n = 53) and patients with
      pancreatic maldigestion syndromes (n = 49). Pancreatic elastase was measured
      immunologically, using a new enzyme immunoassay according to the sandwich
      technique. RESULTS: Spot stool immunoreactive elastase activity in controls
      ranged from 136 to 4,400 micrograms/g. Ninety five percent of all values where
      within 175 to 1,500 micrograms/g. The lower limit of normal was defined as 150
      micrograms/g. No significant decrease of immunoreactivity was found when stool
      samples were stored at room temperature over five days. The assay variability
      calculated from 10 consecutive assays of a single fecal sample gave coefficients
      of variation ranging from 3.3 to 6.3% for intraassay-variability and from 4.1 to
      10.2% for interassay-variability. There was a good correlation between the output
      of elastase compared to lipase output with correlations coefficients of 0.821 in
      controls and 0.905 in patients with impaired pancreatic function. In stool
      samples of 49 patients with exocrine pancreatic insufficiency the concentration
      of fecal elastase was significantly lower (P < 0.001) compared to controls and
      patients with Crohn or coeliac disease. Elastase immunoreactivity showed higher
      sensitivity and specificity as compared to fecal chymotrypsin. Furthermore, in
      contrast to fecal chymotrypsin, the test results were unaffected by pancreatic
      enzyme replacement therapy. CONCLUSION: These results indicate that fecal
      immunoreactive elastase may be recommended as a new, non-invasive easy-to-perform
      tubeless pancreatic function test with a high sensitivity and specificity in
      comparison with healthy controls.

PMID- 8761140
TI  - [Profile of p53 mutations and abnormal expression of P53 protein in 2 forms of
      esophageal cancer].
AB  - AIMS AND METHODS: p53 tumor suppressor gene is involved in the development of
      esophageal cancer. However, its role is not precisely defined in the two types of
      cancer, squamous cell carcinoma and adenocarcinoma developed in Barrett's
      esophagus. The aim of this work was to compare the frequency and type of mutation
      of the p53 gene and the expression of the p53 protein in a series of 21 squamous
      cell carcinomas and 27 adenocarcinomas of the esophagus in a single institution.
      p53 protein accumulation was assessed by immunohistochemistry with the monoclonal
      antibody PAb 1801. The mutations of exons 5 to 8 of p53 gene were detected by
      denaturating gradient gel electrophoresis, and sequenced. RESULTS: A mutation of
      the p53 gene and/or an accumulation of the p53 protein were found in 85% of
      squamous cell carcinomas and 92% of adenocarcinomas, respectively. The profile of
      mutations differed with the type of tumor; large predominance of transitions on
      CpG dinucleotides in adenocarcinomas suggesting an endogenous mechanism, high
      percentage of transversions in squamous cell carcinomas suggesting a direct
      effect of carcinogens present in tobacco and alcohol. CONCLUSION: Mutation of the
      p53 gene is a very frequent event in the two types of esophageal cancer. The
      mechanism responsible for these mutations is different in squamous cell
      carcinomas and adenocarcinomas developed in Barrett's esophagus.

PMID- 8761141
TI  - [Expression of hepatocyte growth factor and its receptor, C-Met in human
      digestive tissues and different gastric and colonic cancer cell lines].
AB  - OBJECTIVES AND METHODS: Hepatocyte growth factor (HGF) and its receptor c-Met
      exert mitogene and motogene activities in digestive tissues. The aim of the study
      was a) to detect and localize these proteins in adult human digestive mucosae,
      liver and pancreas, using western immunoblotting and immunohistochemistry with
      anti-HGF and c-Met antibodies and b) to identify the receptor in three digestive
      cancer cell lines. RESULTS: HGF and c-Met were detected by the two techniques
      used in esophagus, fundus, antrum, duodenum, cecum, colon and rectum where they
      were localized in epithelial and sometimes lamina propria cells. HGF and c-Met
      were also present in hepatocytes, and c-Met in pancreatic endocrine cells. c-Met
      was identified in human gastric HGT-1 and rat colon DHD/K12 cancer cells. HGF (40
      ng/mL) scattered colonies formed by these cells as well as human T84 colon cancer
      cells. CONCLUSIONS: Our findings demonstrate the presence of HGF and c-Met in all
      human digestive tissues and are compatible with the implication of HGF in
      metastatic processes of digestive cancers.

PMID- 8761142
TI  - [Ano-rectal and colonic complications of suppositories and enemas].

PMID- 8761143
TI  - [There is life after liver transplantation].

PMID- 8761145
TI  - [Side effects of interferon-alpha].

PMID- 8761144
TI  - [Pregnancy after hepatic transplantation: what is the maternal risk?].
AB  - OBJECTIVES AND METHODS: We report 7 pregnancies which occurred from 1988 to 1995
      in 5 women who underwent liver transplantation. The immunosuppression regimen
      associated cyclosporine, azathioprine and prednisone. RESULTS: Mean age at
      conception was 25. During pregnancy, cholestasis occurred in 2 women. None of the
      patients experienced rejection. An increase in serum creatinine was observed in 3
      cases. Serum uric acid increased in the third trimester of pregnancy in 6 cases,
      associated with arterial hypertension in 3 cases. In 4 cases, toxemia led to
      premature delivery. Seven childbirths occurred between the 34th and 38th week of
      gestation, by vaginal delivery (n = 3) or caesarean section (n = 4). Newborn
      weights ranged from 1,350 g to 3,100 g. A favorable outcome was observed in all
      mothers, with a follow-up ranging from 2 months to 7 years after delivery.
      CONCLUSION: These results suggest that a successful pregnancy is possible after
      liver transplantation in young women with normal hepatic function and treated
      with cyclosporine. The risk of toxemia is mainly related to renal function before
      pregnancy.

PMID- 8761146
TI  - [Hemorrhagic pancreatic cystadenocarcinoma with colonic fistula. An unusual mode
      of manifestation].
AB  - We report a case of a cystadenocarcinoma of the pancreatic tail, in a 85-year-old
      man. This tumor was successively revealed by a wirsungorrhagia and a hemorrhagic
      pancreatico-colic fistula. To our knowledge, it's an exceptional revelation of a
      pancreatic cystadenocarcinoma and the first case reported in the literature.

PMID- 8761147
TI  - [Acute pancreatitis disclosing an uncommon form of annular pancreas].
AB  - We report a case of an acute pancreatitis revealing an annular pancreas
      associated with a pancreas divisum. Diagnosis was performed by endoscopic
      retrograde pancreatography with successful injection of major and minor papillae.
      Coexistence of pancreas divisum and annular pancreas is a rare congenital
      anomaly. Our case is original because the annular duct system encircling the
      duodenum is the ventral pancreas duct.

PMID- 8761148
TI  - [Imaging of ciliated hepatic or biliary cysts. 4 cases].
AB  - Four patients with ciliated hepatic cysts, a rare and benign lesion, were
      examined between 1990 and 1994. Imaging features were compared to 12 previous
      cases. All lesions were revealed by US, and were hypoechoic in 3 cases, and
      anechoic in 1 case. All lesions were less than to 4 cm in diameter, and were well
      defined, unilocular, isolated, and located in subcapsular areas, usually in the
      medial segment of the left lobe of the liver (3 cases). In one case, the cyst was
      found in the gallbladder wall. The lesions were low density on pre- and post
      contrast CT scan (performed in 2 cases), strongly hyperintense on T2-weighted MR
      images (2 cases), and had a variable signal intensity on T1-weighted MR images.
      One patient underwent percutaneous guided biopsy but no diagnosis was obtained.
      None of the patients had preoperative diagnosis and all underwent surgery.
      Diagnosis was confirmed by histopathologic examination of the resected specimen.
      Ciliated hepatic cysts may be suspected in this study and in the literature.
      Diagnostic criteria are as follows: hypoechogenic mass less than 4 cm in
      diameter, located in the subcapsular area of the medial segment of the left lobe
      of the liver.

PMID- 8761149
TI  - [Primary leiomyosarcoma of the liver 37 years after successful treatment of
      hereditary retinoblastoma].
AB  - In patients successfully treated for hereditary retinoblastoma, the risk of
      developing a second non-ocular tumor has been reported. We report the first case
      of primary hepatic leiomyosarcoma in a 39 year-old woman who has been treated 37
      years before for hereditary retinoblastoma of the left eye. The patient presented
      with right upper quadrant abdominal pain and fever. Histological diagnosis was
      made by liver biopsy. As surgical resection was impossible, chemotherapy with
      epirubicin, then ifosfamide, etoposide and cisplatin was performed. The patient
      died 22 months after diagnosis. Genetic abnormalities observed in hereditary
      retinoblastoma, which probably resulted in a predisposition to the development of
      hepatic cancer in this patient, were not investigated.

PMID- 8761150
TI  - [Cytomegalovirus infection in hemorrhagic rectocolitis treated with
      cyclosporine].

PMID- 8761151
TI  - [Treatment of colorectal anastomotic stenosis with metal endoprosthesis. A 8
      month follow-up].

PMID- 8761152
TI  - [Pulmonary metastases of cancer of the colon].

PMID- 8761153
TI  - [Turner syndrome and digestive telangiectasis: an additional value of estrogen
      progestational treatment].

PMID- 8761154
TI  - [Multiple isolated hepatic metastases of cystic aspect of prostatic
      adenocarcinoma].

PMID- 8761155
TI  - [Hyper-ferritinemia and Gaucher disease].

PMID- 8761156
TI  - [Corynebacterium xerosis endocarditis associated with alcoholic cirrhosis].

PMID- 8761157
TI  - [Addison disease: a rare cause of elevated serum aminotransferase activity].

PMID- 8761159
TI  - Locomotor activity and non-photic influences on circadian clocks.
AB  - Some of the main themes in this review are as follows. 1. The notion that non
      photic zeitgebers are weak needs re-examining. Phase-shifts to some non-photic
      manipulations can be as large as those to light pulses. 2. As well as being able
      to phase-shift and entrain free-running rhythms, non-photic events have a number
      of other effects: these include after-effects of entrainment, period changes, and
      promotion of splitting. 3. The critical variable for non-photic shifting is
      unknown. Locomotor activity is more likely to be an index of some other necessary
      state rather than being causal itself. This index may be better when tendencies
      to move are channelled into easily measured behaviours like wheel-running. 4.
      Given ignorance about the critical variable, quantification of activity may be
      the best presently available measure of zeitgeber intensity. Therefore, the
      behaviour during non-photic manipulations must be examined as carefully as the
      shifts themselves. When no phase-shifting follows manipulations such as IGL
      lesions or serotonin depletion, if the animals are inactive, then little can be
      inferred. 5. Lack of information on the critical variable(s) for non-photic
      shifting makes it problematic to compare data from studies using different non
      photic manipulations. However, the presence of locomotor activity (or its
      correlate) does appear to be necessary for triazolam to produce shifts. 6.
      Novelty-induced wheel-running in hamsters depends on the NPY projection from the
      IGL to SCN. It remains to be determined how important NPY is in other species or
      in clock-resetting by other manipulations, but methods are now available to study
      this. 7. Interactions between photic and non-photic zeitgebers remain virtually
      unexplored, but it is evident that photic and non-photic stimuli can attenuate
      the phase-shifting effects of each other. Interactions are not purely additive or
      predictable from PRCs. 8. The circadian system does more than synchronize free
      running rhythms to the solar day. Its non-photic functions and their interactions
      with photic inputs probably account for some of the anatomical complexity of
      circadian circuitry.

PMID- 8761160
TI  - Sexually transmitted diseases in animals: ecological and evolutionary
      implications.
AB  - Sexually transmitted diseases (STDs) have been generally thought of as a small
      subset of infectious diseases, rather than as an important group of diseases that
      occur in numerous species. In this paper, we have (1) briefly reviewed
      theoretical studies on the dynamics of STDs; (2) documented the distribution of
      STDs in the animal kingdom; and (3) investigated whether STDs have
      characteristics which distinguish them from other infectious diseases. The
      dynamics of STDs should differ from those of ordinary infectious diseases because
      their transmission depends on the frequency rather than density of infectives.
      With this type of transmission, there is no threshold density for disease spread,
      and the conditions for host-pathogen coexistence are more restrictive.
      Nevertheless, a wide variety of disease characteristics may allow a sexually
      transmitted pathogen to coexist with its host. We found over 200 diseases for
      which there was evidence of sexual transmission. They occurred in groups as
      diverse as mammals, reptiles, arachnids, insects, molluscs and nematodes.
      Sexually transmitted pathogens included protozoans, fungi, nematodes, helminths,
      and cancerous cell lines, as well as bacteria and viruses. Detailed comparison of
      the characteristics of sexually transmitted mammalian diseases with those that
      are transmitted by non-sexual means, showed that STDs cause less mortality, are
      longer-lived in their hosts, are less likely to invoke strong immune responses,
      have narrower host-ranges, and show less fluctuation in prevalence over time.
      These shared features are related to mode of transmission rather than either host
      or pathogen taxonomic affiliation. This suggests an evolutionary explanation
      based on shared ecologies rather than one based on phylogenetic history.

PMID- 8761161
TI  - Cerebral palsy, perinatal depression and low ponderal index.
AB  - To determine whether asymmetric growth restriction, abnormally lean body
      morphology, is associated with cerebral palsy (CP) in infants born with perinatal
      depression, perinatally depressed Collaborative Perinatal Project infants were
      assessed. Rates of ponderal index less than 5% for gestational age and race (low
      PI), a marker for asymmetric growth, were compared in infants either
      neurologically normal or having CP at 7 years of age. Low PI was associated with
      CP in infants with Apgar scores of 0 to 3 at 10, 15 or 20 minutes in both of
      these groups, after exclusion of small-for-gestational-age infants, and was a
      significant individual correlate of cerebral palsy with multiple logistic
      regression. The attributable risk of cerebral palsy related to low Pl was 12.4%.

PMID- 8761162
TI  - Early infant grasping involves radial fingers.
AB  - Halverson's hypothesis states that prehension gradually develops from ulnar to
      forefinger holding. This hypothesis was tested by measuring the grip force of
      individual fingers (digits II to V) in 36 healthy children from 2.5 to 7 months
      of age. The results dismissed Halverson's hypothesis, since it was shown that
      from an early age the index finger played a leading role in grasping, usually
      contacting and initiating the grasp prior to the other fingers and producing a
      stronger grip force.

PMID- 8761163
TI  - Functional motor outcome in children with myelomeningocele: correlation with
      anatomic level on prenatal ultrasound.
AB  - Fifteen children with prenatally diagnosed myelomeningocele were followed for at
      least three years to determine the relations between prenatal anatomic level
      visualized on high-resolution ultrasound, radiographic level, neuromotor level
      and functional motor outcome. Prenatal anatomic level accurately predicted
      neuromotor level and functional motor outcome in 12 of the children and was a
      better predictor than motor level at birth. Clinicians involved in prenatal
      counseling may use the anatomic level determined on high-resolution ultrasound to
      discuss motor prognosis with families.

PMID- 8761164
TI  - An exploration of feeding difficulties in children with Down syndrome.
AB  - Detailed examination of several aspects of feeding was carried out on a
      representative sample of a defined geographical population of children with Down
      syndrome. The examination included standardised assessments both of oral-motor
      function and of parent-child interaction. The findings suggest that the
      development of oral-motor function in children with Down syndrome not only lags
      behind intellectual development, but also follows an aberrant pathway. In
      particular, specific aspects of tongue and jaw function were impaired together
      with problems initiating and maintaining a smooth sequence of feeding actions.
      Also, parent-child interactions, as in studies on play, tended to be more
      controlling. Parents of children with Down syndrome do not spontaneously report
      the extent of their child's feeding problems unless specific enquiry is made,
      preferably accompanied by observation of feeding.

PMID- 8761165
TI  - Swallow function in children with Down syndrome: a retrospective study.
AB  - The swallow behavior of 19 children with Down syndrome was reviewed. Findings
      suggest their oral phase may be impacted by oral hypersensitivity which can
      interfere with their acceptance of textured foods. A disordered pharyngeal phase
      was identified in 16 of the children, with aspiration occurring in 10 of the 19
      children studied. Aspiration identified was silent for eight of these 10 children
      with cough data and did not correlate with the severity of their oral phase.
      Aspiration was, therefore, felt to warrant consideration as a factor in the
      respiratory illness so often seen in this population.

PMID- 8761166
TI  - Home mechanical ventilation of children.
AB  - The medical records of 89 ventilator-assisted children followed at the University
      of Michigan Medical Center from 1978 to 1993 were reviewed. The status of these
      children was remarkably stable. Parameters of communication, nutrition,
      education, and mobility changed very little over time, and fewer than half had to
      be re-admitted. Children aged 9 to 12 years had the most nursing hours; in terms
      of diagnosis, those with spinal cord injury and bronchopulmonary dysplasia had
      the most. The younger children had the longest initial hospital stay and the most
      re-admissions. The authors conclude that appropriate rehabilitation during the
      initial hospitalization can minimize later changes, instability and
      rehospitalizations, and that careful follow-up and periodic evaluation can
      improve the patients' health and function.

PMID- 8761167
TI  - Developmental neural abnormalities and seizures in epidermal nevus syndrome.
AB  - The epidermal nevus syndrome (ENS) is an unusual neurocutaneous disorder
      consisting of the combination of an epidermal nevus and a central nervous system
      (CNS), ophthalmological, and/or skeletal abnormality. The study reports four new
      patients with ENS. Each had a confirmatory biopsy of the epidermal nevus,
      abnormal neurological examination findings, and documented CNS anatomical studies
      by imaging or autopsy. The paper also reviews the literature in English to
      determine neurological abnormalities found in skin-biopsy-proven cases of ENS.
      Hemi-atrophy, hemimegalencephaly, migrational abnormalities and vascular
      anomalies were found to be the most frequent intracranial abnormalities
      associated with ENS. Seizures and/or disabling moderate to severe developmental
      delays were present in a majority of patients. Seizure onset during the neonatal
      period or early infancy was associated with major hemispheric malformations.
      Neuroectodermal-derived ocular lesions were often bilateral. No consistent
      relation between laterality of the nevus and laterality of CNS abnormalities was
      found, supporting the gene mosaicism theory of pathogenesis.

PMID- 8761168
TI  - Visual impairment in preterm children with periventricular leukomalacia--visual,
      cognitive and neuropaediatric characteristics related to cerebral imaging.
AB  - Thirteen preterm children, aged 4 to 14 years, with visual impairment due to
      periventricular leukomalacia (PVL) were evaluated for visual function,
      intellectual level, cognitive profile and motor function. Their visual impairment
      was characterized by low acuity, crowding, visual field defects and ocular
      motility disturbances. Their cognitive profile was uneven, often with
      considerably higher scores on verbal than on visual-spatial tasks. Nine children
      had normal intelligence, three had mild mental retardation and one had severe
      mental retardation. In all the children, visual impairment was complicated by
      visual perceptual difficulties, accounting for their greater visual handicap than
      would be expected from their visual acuities and strabismus alone. Though CT or
      MRI revealed bilateral PVL in all the children, six had no motor impairment
      consistent with cerebral palsy, which is an unexpected finding.

PMID- 8761169
TI  - Cognitive visual dysfunction in a child with cerebral damage.
AB  - Visual impairment as a sequel to cortical damage can be associated with complex
      disorders in cognitive visual function. Such dysfunction can be difficult to
      diagnose with certainty, particularly in children, owing to the child's problems
      of awareness and communication. The authors describe the case of a 13-year-old
      girl whose cerebral damage is apparently accompanied by complex cognitive visual
      disorders. Though she has a good binocular visual acuity, she cannot see rapidly
      moving objects. She has difficulties with orientation, recognising faces and
      cognitive depth perception. Despite an absence of detailed psychometric testing,
      a clinical diagnostic approach such as that used in this case, based on a CT scan
      and careful history-taking and observation, may be helpful in planning
      educational strategies.

PMID- 8761170
TI  - Co-dominant inheritance of hyperekplexia and spastic paraparesis.
AB  - In four generations of a family with autosomal dominant hyperekplexia (startle
      disease), untreated affected adult members had pes cavus and extensor plantar
      responses, as well as hyper-reflexia. Electroencephalography during a startle,
      electromyography, nerve conduction velocities and somatosensory evoked potentials
      were normal. Genetic studies showed linkage to the CSF1R locus on chromosome 5q33
      q35, which includes the glycine receptor. This either represents a variant of
      hyperekplexia with spasticity or suggests that genes for hyperekplexia and a form
      of hereditary spastic paraparesis may be closely linked.

PMID- 8761171
TI  - An update on the investigation of the child with a neuropathic bladder.

PMID- 8761172
TI  - Is monoacylglycerol as an intermediate of triacylglycerol digestion absorbed by
      Aeshna cyanea larvae?
AB  - The isolated digestive juice of Aeshna cyanea larvae hydrolysed trioleoylglycerol
      preferentially at the terminal 1 and 3 positions, yielding 1, 2-dioleoylglycerol
      as first intermediate. Hydrolysis continued to 1- and 2-monooleoylglycerol as
      second intermediate. Separate incubation of monooleoylglycerol revealed that
      hydrolysis could proceed to completion. Inadequate inhibition of mono[1
      14C]oleoylglycerol hydrolysis in the cold and in the presence of the lipase
      inhibitor tetrahydrolipstatin provided no information on whether
      monooleoylglycerol was absorbed in addition to free oleic acid. On the other
      hand, the analogue oleylglyceryl ethers were resistant towards hydrolysis by the
      digestive juice. Both monoethers and both diethers were esterified with [1
      14C]palmitic acid by the homogenate of the midgut wall, whereas esterification in
      vivo occurred only with the monoethers. These were recovered from the haemolymph
      after saponification of the joint diacylglycerol and acyl-0-alkylglycerol
      fraction, indicating that the monoethers had been absorbed and transported into
      the haemolymph. Ingestion of mono-1-0-[3H]octadecylglycerol showed that the ether
      was absorbed unchanged by the midgut epithelium, where the major part of the
      alkyl moiety was oxidized to free fatty acid and incorporated into phospholipids,
      acylglycerols and acyl-0-alkylglycerols. It is concluded from the absorption of
      the analogous monoalkylglyceryl ethers that monoacylglyceryl esters are also
      absorbed by Aeshna larvae.

PMID- 8761173
TI  - Myosin isoforms and their light chains from the ventricular muscle of the
      urodelan amphibian Pleurodeles waltlii: comparison with myosin from skeletal
      muscles.
AB  - Myosin extracted from ventricular muscle of the urodelan amphibian Pleurodeles
      waltlii was analyzed in comparison with myosin extracted from skeletal muscles by
      native, one-dimensional SDS gel electrophoresis and two-dimensional gel
      electrophoresis. Two myosin isoforms were detected in ventricular muscle using
      pyrophosphate gel electrophoresis. These isomyosins contained two types of light
      chain subunits, LC1v and LC2v. Two-dimensional gel electrophoresis showed that
      LC1v comigrated with the slow light chain LC1s, whereas LC2v was characterized by
      a specific mobility, distinct from LC2s and LC2f. Diaphragm muscle was
      characterized by the coexistence of larval and adult myosin isoforms.

PMID- 8761174
TI  - Isolation and characterisation of the class alpha, mu and pi glutathione
      transferases in LLC-PK1 and pig kidney.
AB  - Glutathione S-transferase (GST) isoenzymes from pig kidney cortex and LLC-PK1 (an
      established cell line derived from the pig proximal tubule) were purified by
      affinity chromatography, anionic and cationic chromatofocusing. Purification
      revealed nine isoenzymes in the pig kidney cortex and five isoenzymes in the LLC
      PK1 cell line. SDS-polyacrylamide gel electrophoresis showed that the pig kidney
      cortex isoenzymes were homo- or heterodimeric; LLC-PK1 isoenzymes, however, were
      homodimeric. Isoenzymes from pig and LLC-PK1 showed a higher affinity towards
      glutathione. The isoenzymes were further characterised and divided into the
      different GST classes by studying specific inhibitors, specific substrates and
      immunological properties. Pig GSTs belong to class alpha, mu and pi. The GSTs in
      LLC-PK1 cells, on the other hand, belong to class pi and mu. The isoenzyme
      pattern in LLC-PK1 cells indicates the dedifferentiation of this particular cell
      line compared with the pig kidney cortex.

PMID- 8761175
TI  - Salvage pathway of pyrimidine synthesis: divergence of substrate specificity in
      two related species of teleostean fish.
AB  - For nucleotide synthesis, cells use purine and pyrimidine nucleosides generated
      either through de novo synthesis or through utilization of salvage pathways. In
      the pyrimidine salvage pathway, thymidine is taken up by transport proteins and
      phosphorylated by the enzyme thymidine kinase to thymidine monophosphate. So far,
      all vertebrates analyzed are able to use radioactively labeled thymidine for the
      biosynthesis of nucleotides in brain tissue. However, when standard
      autoradiographic, immunohistochemical and biochemical procedures were applied for
      the detection of the incorporation of tritiated thymidine and the thymidine
      analogue 5-bromo-2'-deoxyuridine into DNA to two species of gymnotiform fish, a
      divergence in substrate specificity has been revealed. Although brain cells of
      the two species, Apteronotus leptorhynchus and Eigenmannia sp., can utilize 5
      bromo-2'-deoxyuridine for pyrimidine synthesis, only Eigenmannia sp. is able to
      incorporate tritiated thymidine into DNA during the S phase of the cell cycle. We
      hypothesize that this inability to use thymidine for nucleotide synthesis is
      caused either by a defect in the transport system mediating the uptake of
      thymidine or by a deficiency in the thymidine kinase of A. leptorhynchus.

PMID- 8761176
TI  - Biochemical evidence for the presence of an unconventional actin protein in a
      prokaryotic organism.
AB  - The ubiquity of actin, like the functional diversity of many associated proteins,
      raises a question concerning diversification of motility mechanisms and thus the
      emergence of an elementary functional system. Our aim was to investigate, in
      particular, mobiles prokaryotics cells as Synechocystis lacking cilia and
      flagella, search for actin essential properties and then locate the molecular
      behaviours. Here we report the presence and purification of a 56-kDa (apparent
      molecular weight) prokaryotic protein that polymerizes to form filaments,
      activates myosin Mg(++)-ATPase activity, inhibits DNase-1 activity and affords
      close antigenic homology to skeletal actin. This protein was found to be
      associated with thylakoid membranes and extracted in the presence of Triton X
      100.

PMID- 8761177
TI  - Mouse and rat cystatin C: Escherichia coli production, characterization and
      tissue distribution.
AB  - Recombinant mouse (Mus musculus) and rat (Rattus norvegicus) cystatin C were
      produced by expression in Escherichia coli, isolated and functionally
      characterized. The mouse and rat inhibitors were both fully active in titrations
      of papain. Determination of equilibrium constants for dissociation (Ki) for their
      complexes with the target proteinase, cathepsin B, produced values not largely
      different from that for human cystatin C (Ki 0.07-0.13 nM). Rabbit antisera
      against mouse and rat cystatin C were produced and used for improved affinity
      purification of the recombinant inhibitors. Affinity purified immunoglobulins
      isolated from the antiserum against mouse cystatin C were used for construction
      of a sensitive enzyme-linked immunosorbent assay. The assay was used to
      demonstrate a high degree of immunological cross-reactivity between mouse and rat
      cystatin C and could be used for cystatin C quantification in mouse and rat
      tissue homogenates. All tissues analyzed contained cystatin C, with a relative
      content very similar to that of human tissues. For all species, brain tissue
      contained the highest cystatin C amounts and liver the lowest, whereas kidney,
      spleen and muscle tissues were intermediate in content. In the mouse, a notable
      high cystatin C content in parotid gland tissue was observed. The high degree of
      similarity in distribution pattern and functional properties for mouse, rat and
      human cystatin C indicates that a murine model should be relevant for studies of
      the human disease, hereditary cystatin C amyloid angiopathy.

PMID- 8761178
TI  - The Xenopus laevis homologue of the 64-kDa subunit of cleavage stimulation
      factor.
AB  - Cleavage stimulation factor (CstF) is composed of three subunits of 50, 64 and 77
      kDa, respectively. We report here the identification of a cDNA clone from Xenopus
      laevis encoding a homologue of the 64-kDa subunit of human CstF. Comparative
      sequence analysis reveals that these two proteins are highly conserved with the
      exception of a unique repeat structure found in the human, but not in the X.
      laevis, protein. Analysis of expression of this mRNA during X. laevis tadpole
      development indicates a requirement for this protein throughout all stages of
      development.

PMID- 8761179
TI  - Rational disease-modifying anti-rheumatic drug (DMARD) therapy: is it possible?

PMID- 8761180
TI  - A novel action of glucocorticoids--NF-kappa B inhibition.

PMID- 8761181
TI  - Expression of cyclooxygenase-2 in human and an animal model of rheumatoid
      arthritis.
AB  - An inducible form of cyclooxygenase-2 (COX-2) has been shown to be upregulated in
      vitro by various pro-inflammatory agents, such as lipopolysaccharide, IL-1 and
      TNF, COX-2 appears to be responsible for the increase in prostaglandin synthesis
      at the site of inflammation. To examine the involvement of COX-2 in inflammation,
      we analysed the expression of this gene in human rheumatoid arthritis (RA) and in
      rat adjuvant-induced arthritis. Immunocytochemical studies of synovial membrane
      biopsies from human RA, osteoarthritic (OA) and normal joints using a COX-2
      specific antibody showed positive staining in RA, but not in normal synovial
      membranes. Specifically, expression of COX-2 was detected in synovial lining
      cells, lymphoid aggregates and endothelial cells of blood vessels. Although some
      positive staining was observed in the OA joints, the number of stained cells was
      dramatically lower and the staining of the cells was less intense than in the
      rheumatoid tissue. By reverse transcription and polymerase chain reaction
      analysis, COX-2 mRNA was detected in the rat adjuvant arthritic limb, whereas no
      COX-2 mRNA was detectable in the normal limb. These observations indicate that
      COX-2 expression is upregulated in inflammatory joint disease and that COX-2 is a
      potential therapeutic target for specific inhibition.

PMID- 8761182
TI  - A single intra-articular injection of liposomally conjugated methotrexate
      suppresses joint inflammation in rat antigen-induced arthritis.
AB  - In this study, we sought to determine whether liposomal preparations containing a
      phospholipid conjugate of methotrexate and dimyristoylphosphatidylethanolamine
      (MTX-gamma-DMPE) incorporated within their lipid membranes are effective in
      suppressing established joint inflammation in a monoarticular model of arthritis
      in the rat. Arthritis was induced in the right knee joint of Lewis rats. The rats
      were treated with a single intra-articular injection of either free methotrexate
      (MTX), liposomal MTX [MTX-multilamellar vesicles (MLV)-1.2 microns or MTX-small
      unilamellar vesicles (SUV)-100 nm], control liposomes (E-LIPO) or saline into the
      inflamed knee 7 days after arthritis induction. There was no significant
      difference in knee swelling in MTX-, saline- and E-LIPO-treated rats up to 21
      days after treatment. However, MTX-MLV treatment produced a significant reduction
      in knee swelling (26.5 +/- 6.0%: mean +/- S.E.M.) 1 day after intra-articular
      injection compared with MTX (3.5 +/- 3.5%) and MTX-SUV (14.4 +/- 2.4%),
      respectively. Over the next 20 days, knee swelling in MTX-MLV-treated rats fell
      progressively and almost returned to normal. MTX-MLV treatment also inhibited the
      cellular infiltration associated with the arthritis. Large multilamellar
      liposomal preparations of MTX-gamma-DMPE are more effective than free MTX and MTX
      SUV in suppressing inflammation. Their differential effects in treating the
      antigen-induced arthritis model are related to their retention within the joint
      space.

PMID- 8761183
TI  - Anti-ganglioside antibodies in patients with rheumatoid arthritis complicated by
      peripheral neuropathy.
AB  - Gangliosides are a diverse class of glycolipids found in the plasma membrane of
      mammalian cells and are particularly abundant in cells of the nervous system.
      Serum antibodies to gangliosides have been detected in various neurological
      disorders with some evidence that they play a pathogenic role. In this study, we
      have investigated whether anti-ganglioside antibodies were elevated in a group of
      patients with rheumatoid arthritis (RA) who developed peripheral neuropathy (PN).
      An ELISA technique was used to test sera from 28 patients with RA and PN. 38 RA
      patients without PN and 20 normal controls for the presence of IgG and IgM anti
      GM1 and sulphatide antibodies. The patients with RA and PN had higher pain scores
      (P < 0.005), more extra-articular features (P < 0.05), higher erosive scores (P <
      0.0001), lower haemoglobin (P < 0.005), higher ESR (P < 0.001) and were more
      often on disease-modifying drugs (P < 0.05). Twelve RA patients with PN (43%),
      but only two RA controls (5%), had positive titres against one or more
      gangliosides (P < 0.001). The neurologic disability score (NDS) correlated with
      RA duration (P < 0.05), and with levels of IgM anti-GM1 (P < 0.001) and IgM anti
      sulphatide (P < 0.05) antibodies. We conclude that PN is more common in patients
      with severe rheumatoid disease, and a significant proportion have elevated levels
      of anti-ganglioside antibodies.

PMID- 8761184
TI  - Telomere reduction in scleroderma patients: a possible cause for chromosomal
      instability.
AB  - We have hypothesized that the chromosomal instability observed in scleroderma
      patients and their family members may result from the loss of long stretches of
      the telomeric repeat which is found at the ends of all linear chromosomes. We
      examined the telomere lengths in scleroderma (SSc) patients (n = 43), their
      family members (n = 182) and in age-matched controls (n = 96) using restriction
      fragment length polymorphism (RFLP) and chemiluminescent labelled probes. The
      average loss of telomeric DNA in SSc patients and family members was found to be
      3 kb when compared to the controls. This loss was not related to age or the
      duration of the disease. These results may reflect a genetic predisposition for
      chromosomal instability in these families, or exposure to a common environmental
      agent. A wide variety of common environmental agents are known to produce
      chromosomal aberrations: these include fungicides, pesticides, air pollutants and
      drugs. Scleroderma-like syndromes may be induced by some of these agents.

PMID- 8761185
TI  - Does exposure to immunosuppressive therapy increase the 10 year malignancy and
      mortality risks in rheumatoid arthritis? A matched cohort study.
AB  - Rheumatoid arthritis (RA) is associated with increased mortality and an increased
      risk of neoplasms of the immune system (NIM). To establish whether
      immunosuppressive therapy alters these risks, a matched cohort study was
      conducted. The exposed cohort were 259 RA patients, resident in the UK, who first
      received immunosuppressive drugs (mainly azathioprine, cyclophosphamide and
      chlorambucil) between 1979 and 1982. The unexposed cohort were 259 patients
      matched for age, sex and disease, resident in the USA, who had never received
      immunosuppressives. Both cohorts had no prior reported malignancies and were
      followed for 10 yr. There was a small increase in mortality in the exposed
      compared to the unexposed cohort. Most of the excess deaths were due to
      malignancy. The relative risk (RR) of developing malignancy [1.5 (95% CI 0.9
      2.3)] was lower than the RR of dying from malignancy [4.2 (95% CI 1.7-10.0)]. The
      RR of developing a NIM in the immunosuppressive-exposed group was 7.0 (95% CI 0.9
      56.5). These results may be explained in part by differences in cancer
      registration and death rates between the UK and the USA. Nevertheless, the
      results suggest that exposure to immunosuppressive therapy increases the 10 yr
      malignancy risk in RA, but not mortality from other causes.

PMID- 8761186
TI  - Correlates of functional disability in early rheumatoid arthritis: a cross
      sectional study of 706 patients in four European countries.
AB  - In this cross-sectional study of 706 European patients with rheumatoid arthritis
      (RA) of < or = 4 yr duration, we examined possible correlates of functional
      disability assessed by the Health Assessment Questionnaire. First, we examined a
      subsample of 237 Norwegian patients. The Ritchie index, sex, age, erythrocyte
      sedimentation rate (ESR) and disease duration correlated significantly with
      disability, whereas serum rheumatoid factor, hand X-ray changes and educational
      level did not. Subsequently, we cross-validated these findings in a similar
      sample of 469 French, Dutch and Northern Irish patients. The results supported
      the Ritchie index, sex, ESR and disease duration as significant correlates of
      disability, whereas rheumatoid factor, age and education were not significantly
      correlated with disability. The correlation between X-ray changes and disability
      could not be cross-validated. The main findings of this study are that female sex
      correlates significantly with disability even early in the course of RA, whereas
      the rheumatoid factor does not.

PMID- 8761187
TI  - Raynaud's phenomenon in rheumatoid arthritis.
AB  - The aim of this study was to evaluate the prevalence of Raynaud's phenomenon in
      patients with rheumatoid arthritis (RA), and to relate this symptom to clinical,
      radiological and serological characteristics of the patients. All relevant
      information was retrospectively obtained from the standardized clinical records
      of 322 RA in-patients first admitted to the Rheumatology Unit of Brest University
      Medical School. Raynaud's phenomenon was found in 54 (17.2%) of 322 RA patients.
      There was no significant correlation between demographic, clinical or
      radiological characteristics. However, the subgroup of RA patients with Raynaud's
      phenomenon had a slightly higher prevalence of vasculitis than the subgroup
      without Raynaud's phenomenon. CRP level and C4 level were found to be lower in
      the former than in the latter group, whereas ESR and various serological findings
      (rheumatoid factor, antinuclear antibodies) were comparable in the two groups. We
      conclude that the prevalence of Raynaud's phenomenon is high in French RA in
      patients, and that some clinical and biological abnormalities (vasculitis, low
      CRP level and low C4 level) suggest an association between Raynaud's phenomenon
      and vasculitis in a few cases, whereas this association might be fortuitous in
      the remainder.

PMID- 8761188
TI  - Evaluation of a Dutch version of the AIMS2 for patients with rheumatoid
      arthritis.
AB  - DUTCH-AIMS2, a Dutch version of AIMS2 and successor to DUTCH-AIMS, is an
      instrument to assess health status among patients with rheumatic diseases. It
      provides measurements of 12 areas of health status on scales for health status
      proper, satisfaction, attribution and arthritis impact. We assessed the
      reliability of its scales in terms of internal consistency and their validity
      according to both internal standards and external standards. Correctly completed
      questionnaires were returned by 231 RA patients and 131 controls. Internal
      consistency coefficients for the health status scales ranged from 0.66 and 0.89,
      but most exceeded 0.80. Within-scale factor analyses produced single factors in
      all composite health status scales for both patients and controls, with only two
      exceptions. Factor analysis also identified a physical, social and psychological
      dimension among 11 areas of health. External validity was established by strong
      correlations between DUTCH-AIMS2 health status scales and functional class,
      laboratory parameters, and self-assessments of fatigue, loneliness, pain,
      functional disability and social support. DUTCH-AIMS2 is acceptably reliable and
      valid for use in a variety of settings.

PMID- 8761189
TI  - Knee joint space width measurement: an experimental study of the influence of
      radiographic procedure and joint positioning.
AB  - We studied the influence of the radiographic procedure and joint positioning on
      knee joint space width (JSW) in 10 healthy volunteers, and the intrareader
      reproducibility of JSW measurements on radiographs performed 2 weeks apart using
      a standardized procedure. Results show that a 5 or 10 downward inclination of the
      X-ray beam and 15 or 30 of induced external foot rotation significantly reduced
      JSW. In contrast, knee flexion increased JSW. The mean differences and S.D. in
      the measurement of JSW between two sets of radiographs taken 2 weeks apart were
      not statistically significant, ranging from -0.07 mm (S.D. 0.38) to 0.020 mm
      (S.D. 0.38). Our findings indicate that modifications in knee flexion, foot
      rotation and X-ray beam inclination influence JSW. Therefore, standardization of
      joint positioning and of the radiographic procedure is necessary to obtain
      comparable radiographic images on successive X-rays.

PMID- 8761190
TI  - Assessment of the efficacy of sacroiliac corticosteroid injections in
      spondylarthropathies: a double-blind study.
AB  - Despite previously carrying out a first open study of sacroiliac injection of
      long-acting corticosteroid, it was not possible to evaluate the role of a placebo
      effect. We therefore performed a double-blind study in 10 patients/13
      articulations, suffering painful sacroiliitis. At 1 month, 5/6 sacroiliac joints
      injected with corticosteroid described a relief of > 70%, in comparison to 0/7 of
      the placebo group (P < 0.05). Dolometry showed a marked decrease in the
      corticosteroid group from (mean +/- S.E.M.) 6.8 +/- 0.6 to 1.3 +/- 0.3, and
      decreases were mild in the placebo group: 7.0 +/- 0.6 to 5.2 +/- 0.5 (P < 0.005).
      Six of the seven sacroiliac joints of the placebo group and two patients with
      failure and relapse of the corticosteroid group were reinjected with
      corticosteroid. At 1 month, 12/14 (85.7%) were assessed as having a good result.
      Results were still significant at 3 months (62%) and 6 months (58%). Tolerance
      was good or very good in 86% of the cases, and we did not report any notable
      complication. This technique is safe and very efficient, and it has to be
      considered more widely in patients with contraindications or complications with
      NSAID, or if the medical treatment is unable to control sufficiently the active
      sacroiliitis.

PMID- 8761191
TI  - A stiff collar for the treatment of rheumatoid atlantoaxial subluxation.
AB  - Conservative treatment of atlantoaxial subluxation (AAS) has tended to be rather
      passive, since there has been a lack of effective tools. The stabilizing effect
      of a stiff collar in the treatment of AAS was evaluated. Fifty successive
      rheumatoid patients with unstable AAS were interviewed and examined clinically.
      Lateral view radiographs of the cervical spine were taken in neutral position,
      during flexion and extension without a collar, and during flexion with a stiff
      collar. Seventeen patients did not have cervical symptoms. A stiff collar was
      able to significantly stabilize AAS in more than half of the cases, the effect
      being predictable from neutral-position radiographs. The improvement in bearing
      enhanced the effect of the collar. The means and strategy of conservative
      treatment of AAS are discussed.

PMID- 8761192
TI  - Single-blind randomized controlled trial of an educational booklet for patients
      with chronic arthritis.
AB  - Consecutive new attendees at a rheumatology clinic were randomly allocated to one
      of three groups. All groups received routine care, but one received no other
      intervention, one an educational booklet on arthritis and one the booklet plus
      instruction from a health professional. Prior to intervention, all groups had
      similar knowledge. Nottingham Health Profile (NHP) and Health Assessment
      Questionnaire (HAQ) score. After 6 weeks, the knowledge score was significantly
      increased in both groups given the booklet, but not in the control group. The
      group instructed by a health professional showed no greater increase than the
      group given the booklet alone. Increased knowledge was not associated with
      improved clinical status and no group showed a significant change in NHP or HAQ
      scores. Nearly all patients said they found the booklet useful.

PMID- 8761193
TI  - Rheumatology in Israel.

PMID- 8761194
TI  - The cost of rheumatoid arthritis.
AB  - This paper uses the Cost of Illness (COI) framework to estimate the cost of
      rheumatoid arthritis (RA) to society in the year 1992-93. By doing so, a clear
      insight is given into the many cost elements of RA treatment and monitoring. This
      paper estimates point prevalence rates of 2.06 and 6.94 1000 persons at risk for
      men and women, respectively, showing that prevalence is three times higher
      amongst women than men. Further to this, prevalence increases with age in both
      sexes, resulting in very high prevalence rates for RA amongst the elderly. The
      total economic impact of RA in England was estimated to be pounds 1.256 billion
      in 1992, of which 52% was a result of production loss caused by RA disability.

PMID- 8761195
TI  - Treatment of rheumatoid arthritis--does it affect society's cost for the disease?
AB  - To assess whether the treatment of rheumatoid arthritis reduces the cost to
      society of the disease, 62 patients were studied retrospectively over an 18 month
      period. The first 6 months (period 1) was the time before treatment with
      remission-inducing drugs (RID). The following 6 month period (period 2) was the
      time when RID treatment was started and suitable doses were evaluated. The last 6
      month period (period 3) was the follow-up period when the results of the
      treatment were evaluated. The cost for drugs, surgical treatment, out-patient
      visits, blood tests and hospitalization days during periods 2 and 3 was
      calculated as 1.6 million SEK. During the same period, the cost for loss of
      productivity to society was reduced by 1.5 million SEK, assuming that the cost to
      society would have been unchanged, compared to period 1, if therapy had not been
      given. In a small group of patients who entered remission, the net saving for
      society exceeded the cost of treatment. The study indicates that the treatment of
      rheumatoid arthritis can lead to a reduced cost to society.

PMID- 8761196
TI  - Polyarteritis nodosa in human immunodeficiency virus infection: report of four
      cases and review of the literature.
AB  - Four patients with HIV infection were diagnosed as having panarteritis nodosa
      type vasculitis in muscle samples taken by biopsy. Fever, weight loss and
      neuromuscular symptoms were the major complaints. All but one were successfully
      treated with a low dose of prednisone. The other patient refused treatment, but
      her muscular complaints did not worsen during 9 months of follow-up. Previously
      reported cases in the literature are reviewed.

PMID- 8761197
TI  - Three year follow-up of a case of giant cell arteritis presenting with a chronic
      cough and upper limb ischaemic symptoms.
AB  - A case of giant cell arteritis presenting in an atypical fashion with respiratory
      and upper limb ischaemic symptoms is described. The subclavian and axillary
      arterial involvement is demonstrated in this case, and followed up with repeated
      angiographic examinations over the next 3 yr. Despite resolution of all symptoms
      and return of pulses and a recordable blood pressure in the ischaemic upper limb,
      there was no angiographic evidence of resolution of the axillary artery stenoses.

PMID- 8761198
TI  - Overexpression of proto-oncogene bcl-2 in rheumatoid synovium.

PMID- 8761199
TI  - Neurological signs in RA patients receiving gold.

PMID- 8761200
TI  - The antiperinuclear factor in spondylarthropathies.

PMID- 8761201
TI  - Patient education: treatment or nice extra. The British experience.

PMID- 8761202
TI  - Co-existent coeliac disease and scleroderma.

PMID- 8761203
TI  - Massive pericardial effusion in scleroderma.

PMID- 8761204
TI  - Rheumatoid arthritis and heparin.

PMID- 8761205
TI  - From twin to singleton.

PMID- 8761206
TI  - Firearm legislation and the Cullen inquiry.

PMID- 8761207
TI  - Teenage drug use.

PMID- 8761208
TI  - Intravenous IgG in Guillain-Barre syndrome.

PMID- 8761209
TI  - New roles for thalidomide.

PMID- 8761210
TI  - Active management of labour.

PMID- 8761211
TI  - Doctors may have to countersign gun applications.

PMID- 8761212
TI  - Selective abortions hit the headlines.

PMID- 8761213
TI  - Quadruple test is available for Down's syndrome.

PMID- 8761214
TI  - Internet sees growth of unverified health claims.

PMID- 8761215
TI  - Health committee backs cradle to grave care.

PMID- 8761217
TI  - Health of the Nation could be better.

PMID- 8761216
TI  - Smoker wins damages against US tobacco company.

PMID- 8761220
TI  - Doctors call for law change on cannabis.

PMID- 8761221
TI  - Russia faces demographic crisis.

PMID- 8761222
TI  - US scientists challenge approval of sweetener.

PMID- 8761224
TI  - Do antimicrobials increase the carriage rate of penicillin resistant pneumococci
      in children? Cross sectional prevalence study.
AB  - OBJECTIVE: To study the correlation of antimicrobial consumption with the
      carriage rate of penicillin resistant and multiresistant pneumococci in children.
      DESIGN: Cross sectional and analytical prevalence study. SETTING: Five different
      communities in Iceland. MAIN OUTCOME MEASURE: Prevalence of nasopharyngeal
      carriage of penicillin resistant pneumococci in children aged under 7 years in
      relation to antibiotic use as determined by information from parents, patient's
      records, and total sales of antimicrobials from local pharmacies in four study
      areas. RESULTS: Total antimicrobial sales for children (6223 prescriptions) among
      the four areas for which data were available ranged from 9.6 to 23.2 defined
      daily doses per 1000 children daily (1.1 to 2.6 courses yearly per child).
      Children under 2 consumed twice as much as 2-6 year olds (20.5 v 10.9 defined
      daily doses per 1000 children daily). Nasopharyngeal specimens were obtained from
      919 children, representing 15-38% of the peer population groups in the different
      areas. Pneumococci were carried by 484 (52.7%) of the children, 47 (9.7%) of the
      isolates being resistant to penicillin or multiresistant. By multivariate
      analysis age (< 2 years), area (highest antimicrobial consumption), and
      individual use of antimicrobials significantly influenced the odds of carrying
      penicillin resistant pneumococci. By univariate analysis, recent antimicrobial
      use (two to seven weeks) and use of co-trimoxazole were also significantly
      associated with carriage of penicillin resistant pneumococci. CONCLUSIONS:
      Antimicrobial use, with regard to both individual use and total antimicrobial
      consumption in the community, is strongly associated with nasopharyngeal carriage
      of penicillin resistant pneumococci in children. Control measures to reduce the
      prevalence of penicillin resistant pneumococci should include reducing the use of
      antimicrobials in community health care.

PMID- 8761225
TI  - Case-control study of risk of dehydrating diarrhoea in infants in vulnerable
      period after full weaning.
AB  - OBJECTIVES: To investigate risk factors for dehydrating diarrhoea in infants,
      with special interest in the weaning period. DESIGN: Case-control study. SETTING:
      Metropolitan area of Porto Alegre, Brazil. SUBJECTS: Cases were 192 children aged
      0-23 months hospitalised with acute diarrhoea and moderate to severe dehydration.
      Controls were 192 children matched for age and neighbourhood who did not have
      diarrhoea in the previous week. MAIN OUTCOME MEASURES: Associations between
      dehydrating diarrhoea and child's age, type of milk consumed, time since breast
      feeding stopped, and breast feeding status. RESULTS: In infants aged < 12 months
      the risk of dehydrating diarrhoea was significantly higher in the first 9 months
      of life (P < 0.001), and in those aged 12-23 months the risk was again greater in
      younger children (12-17 months) (P = 0.03). The type of milk consumed before
      start of diarrhoea episode was strongly associated with dehydration independent
      of socioeconomic, environmental, maternal reproductive, demographic, and health
      services factors. Compared with infants exclusively breast fed, bottle fed
      infants were at higher risk (odds ratio (95% confidence interval) for cow's milk
      6.0 (1.8 to 19.8), for formula milk 6.9 (1.4 to 33.3)). Compared with those still
      breast feeding, children who stopped in the previous two months were more likely
      to develop dehydrating diarrhoea (odds ratio 8.4 (2.4 to 29.6)). This risk
      decreased with time since breast feeding stopped. CONCLUSION: These results
      confirm the protective effect of breast feeding and suggest there is a vulnerable
      period soon after breast feeding is stopped, which may be of relevance for
      developing preventive strategies.

PMID- 8761226
TI  - Drinking, smoking, and illicit drug use among 15 and 16 year olds in the United
      Kingdom.
AB  - OBJECTIVE: To examine patterns of self reported drinking, smoking, and illicit
      drug use among a representative United Kingdom sample of people born in 1979.
      DESIGN: Cross sectional, single phase survey based on a stratified cluster sample
      of 70 United Kingdom secondary schools during March and April 1995. Pupils
      completed a 406 item standardised questionnaire under examination conditions.
      SETTING: United Kingdom state and private secondary schools. SUBJECTS: 7722
      pupils aged 15 and 16. MAIN OUTCOME MEASURES: Reported use of alcohol, tobacco,
      and illicit drugs. RESULTS: Almost all the pupils had drunk alcohol, 36%
      (2772/7689) had smoked cigarettes in the past 30 days, and 42.3% (3264/7722) had
      at some time used illicit drugs, mainly cannabis. 43% (1546/3546) of boys and 38%
      (1529/4009) of girls had tried cannabis. Higher levels of smoking were associated
      with poorer school performance (20.4% (783/3840) with average performance v 44.1%
      (214/486) with below average performance, F = 79.06, P < 0.01). Levels of drug
      use in 15 and 16 year olds in 1995 were higher in Scotland than in England,
      Wales, or Northern Ireland. CONCLUSIONS: Drug experimentation was high among 15
      and 16 year olds, and use of cannabis was particularly high among smokers.
      Cigarette smoking was more common among girls than boys.

PMID- 8761227
TI  - Cigarette advertising and onset of smoking in children: questionnaire survey.
AB  - OBJECTIVE: To investigate uptake of smoking in a cohort of 11 to 12 year olds
      related to awareness of advertised cigarette brands named. DESIGN: Self completed
      questionnaires administered to whole classes of schoolchildren in June 1993 and
      June 1994. SETTING: Primary, middle, and secondary schools in the north and south
      of England. SUBJECTS: 1450 pupils aged 11 and 12 years at the time of the first
      survey. MAIN OUTCOME MEASURES: Onset of smoking and brands smoked by the second
      survey related to cigarette brands named in the first one. Less advertised brands
      were used as the base for calculating odds ratios. RESULTS: Girls who named the
      most advertised brands-namely, Benson and Hedges alone (odds ratio = 2.50, 95%
      confidence interval = 1.18 to 5.30) or Benson and Hedges and Silk Cut (2.15, 1.04
      to 4.42) in the first survey were at greatest risk of taking up smoking by the
      second one. The difference was similar but not significant for boys. Boys and
      girls who named the least advertised brands in the first survey were at no
      greater risk of taking up smoking by the second survey than those who named no
      brands (boys odds ratio = 0.49 (0.24 to 1.01); girls 0.79 (0.38 to 1.62)). New
      smokers were more likely to smoke any available brand (29.5%) or a less
      advertised brand such as Embassy (24.6%) than the most advertised ones, Benson
      and Hedges (19.7%) and Silk Cut (14.8%). Established smokers were more selective,
      only 15% smoking any available brand and 38.3% smoking Benson and Hedges.
      CONCLUSIONS: Cigarette advertising appears to increase children's awareness of
      smoking at a generic level and encourages them to take up the behaviour,
      beginning with any cigarettes which are available and affordable.

PMID- 8761228
TI  - Effect of sports sponsorship by tobacco companies on children's experimentation
      with tobacco.

PMID- 8761229
TI  - Designer drinks and drunkenness amongst a sample of Scottish schoolchildren.

PMID- 8761230
TI  - Frequency of non-fatal heroin overdose: survey of heroin users recruited in non
      clinical settings.

PMID- 8761231
TI  - Routine monitoring of all postoperative outcomes at one year: longitudinal study
      at the Royal National Throat, Nose and Ear Hospital.

PMID- 8761232
TI  - Predictive value of ambulatory blood pressure shortly after withdrawal of
      antihypertensive drugs in primary care patients.
AB  - OBJECTIVE: To determine whether ambulatory blood pressure eight weeks after
      withdrawal of antihypertensive medication is a more sensitive measure than seated
      blood pressure to predict blood pressure in the long term. DESIGN: Patients with
      previously untreated diastolic hypertension were treated with antihypertensive
      drugs for one year; these were withdrawn in patients with well controlled blood
      pressure, who were then followed for one year. SETTING: Primary care. SUBJECTS:
      29 patients fulfilling the criteria for withdrawal of antihypertensive drugs.
      MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative
      predictive value of seated and ambulatory blood pressure eight weeks after
      withdrawal of antihypertensive drugs. RESULTS: Eight weeks after withdrawal of
      medication, mean diastolic blood pressure returned to the pretreatment level on
      ambulatory measurements but not on seated measurements. One year after withdrawal
      of medication, mean diastolic blood pressure had returned to the pretreatment
      level both for seated and ambulatory blood pressure. For ambulatory blood
      pressure, the sensitivity and the positive predictive value eight weeks after
      withdrawal of medication were superior to those for seated blood pressure;
      specificity and negative predictive value were comparable for both types of
      measurement. Receiver operating characteristic curves showed that the results
      were not dependent on the cut off values that were used. CONCLUSION: Ambulatory
      blood pressure eight weeks after withdrawal of antihypertensive drugs predicts
      long term blood pressure better than measurements made when the patient is
      seated.

PMID- 8761234
TI  - How can impact factors be improved?
AB  - Impact factors are widely used to rank and evaluate journals. They are also often
      used inappropriately as surrogates in evaluation exercises. The inventor of the
      Science Citation Index warns against the indiscriminate use of these data.
      Fourteen year cumulative impact data for 10 leading medical journals provide a
      quantitative indicator of their long term influence. In the final analysis,
      impact simply reflects the ability of journals and editors to attract the best
      papers available.

PMID- 8761233
TI  - Neonatal screening for sickle cell disorders: what about the carrier infants?

PMID- 8761235
TI  - Acute angle closure glaucoma masquerading as systemic illness.

PMID- 8761236
TI  - Caring for Older People. Public transport.
AB  - Most older people are mobile and able to use public transport without any
      problems. Those who are hard of hearing or have poor vision and those with
      mobility problems need not be deterred from using public transport. Though the
      design and provision of suitable buses, taxis, and trains is not always optimum,
      many now have imaginative features to help older passengers. Travel by air and
      sea needs extra planning for disabled elderly people, but helpful advice is
      available and much can be done to enable even the most disabled traveller to make
      long journeys confidently and in comfort.

PMID- 8761237
TI  - ABC of work related disorders. Neck and arm disorders.

PMID- 8761238
TI  - Ecstasy and neurodegeneration. Advice is that "less is more".

PMID- 8761239
TI  - Ecstasy and neurodegeneration. No evidence of neurotoxicity exists.

PMID- 8761240
TI  - Ecstasy and neurodegeneration. Tablets often contain substances in addition to,
      or instead of, ecstasy...

PMID- 8761241
TI  - Ecstasy and neurodegeneration. ...such as ketamine.

PMID- 8761242
TI  - Ecstasy and neurodegeneration. gamma-Hydroxybutyrate is a new recreational drug
      that may lead to loss of consciousness.

PMID- 8761243
TI  - Recommendation to avoid all drugs during first trimester is unrealistic.

PMID- 8761244
TI  - Medic Alert UK should start new section for patients with a difficult airway.

PMID- 8761245
TI  - Describing race, ethnicity, and culture in medical research. "White" populations
      also need to be accurately described.

PMID- 8761246
TI  - Describing race, ethnicity, and culture in medical research. Self defined
      ethnicity is unhelpful.

PMID- 8761247
TI  - Describing race, ethnicity, and culture in medical research. Links need to be
      maintained with census definitions.

PMID- 8761248
TI  - Describing race, ethnicity, and culture in medical research. Guidelines will
      encourage the thinking that underpins racism in medicine.

PMID- 8761249
TI  - Addison's disease. Secondary adrenal failure in critically ill patients is
      underrecognised.

PMID- 8761250
TI  - Addison's disease. Adrenal insufficiency should be excluded before thyroxine
      replacement is started.

PMID- 8761251
TI  - Addison's disease. Hydrocortisone should be started immediately adrenal
      insufficiency is considered.

PMID- 8761252
TI  - N of 1 trials. Research is needed into why such trials are not more widely used.

PMID- 8761253
TI  - N of 1 trials. Placebos should be abandoned.

PMID- 8761254
TI  - Blood donation. Britain's blood service is committed to spirit of altruism among
      donors.

PMID- 8761255
TI  - Blood donation. Age limit should be reviewed.

PMID- 8761256
TI  - Relation of C reactive protein to cardiovascular risk factors. Assays would have
      to be developed to measure C reactive protein.

PMID- 8761257
TI  - Relation of C reactive protein to cardiovascular risk factors. H pylori and C
      pneumoniae infections may account for most acute coronary syndromes.

PMID- 8761258
TI  - Drug use in prison. Methadone maintenance in prison needs to be evaluated.

PMID- 8761259
TI  - Drug use in prison. Access to sterile injecting equipment is important.

PMID- 8761260
TI  - National crash call number is needed.

PMID- 8761261
TI  - Light the blue touchpaper and stand well clear.

PMID- 8761262
TI  - AAEM minimonograph #25: single-fiber electromyography.
AB  - Single-fiber electromyography (SFEMG) is a selective recording technique in which
      a needle electrode with a small recording surface in the side is used to identify
      action potentials from individual muscle fibers. The SFEMG parameters of greatest
      clinical use are fiber density (FD) and neuromuscular jitter. FD reflects the
      local organization of muscle fibers within the motor unit; jitter reflects the
      safety factor of neuromuscular transmission at individual neuromuscular
      junctions. SFEMG can be of great value in demonstrating or excluding
      abnormalities in mild or questionable disease of nerve, muscle, or the
      neuromuscular junction. The neuromuscular jitter may be measured during nerve
      stimulation, which is particularly useful in uncooperative patients or when it is
      desirable to control the firing rate precisely, or during voluntary muscle
      activation, which is less subject to technical artifact. The SFEMG findings may
      not be specific to a particular disease, but they frequently increase
      understanding of the disease process by demonstrating abnormal neuromuscular
      transmission or rearrangement of muscle fibers within the motor unit, which
      complements information from more conventional EMG examinations.

PMID- 8761263
TI  - Effects of length changes on Na+ current amplitude and excitability near and far
      from the end-plate.
AB  - Na+ current (INa), membrane capacitance (Cm), action potential (AP) properties,
      and cable properties were studied on the end-plate (E), the end-plate border
      (EB), and extrajunctional (EJ) membrane of rat fast twitch muscle fibers. INa
      normalized to Cm, which is proportional to the density of Na+ channels, was the
      same on the E and the EB and smallest on EJ membrane. The AP threshold was lower
      and rate of rise of the AP was larger at the EB compared with EJ membrane. On the
      E and the EB, Cm and INa did not change in response to changes in fiber length.
      On EJ membrane, INa, Cm, and membrane cable properties changed in a manner
      consistent with folding and unfolding of the sarcolemma during length changes.
      The stiffness of the E membrane may add mechanical stability of the neuromuscular
      junction so that the electrical properties of the end-plate do not change with
      fiber length. The higher density of Na+ channels near the end-plate increases the
      safety factor for neuromuscular transmission by lowering the AP threshold.

PMID- 8761264
TI  - Brain stem reflexes in patients with Wallenberg's syndrome: correlation with
      clinical and magnetic resonance imaging (MRI) findings.
AB  - In spite of the general clinical uniformity of Wallenberg's syndrome (WS),
      individual patients present with a slightly different clinical picture, and
      detailed studies with magnetic resonance imaging (MRI) show differences in the
      topography of the brain stem lesion. Neurophysiological characterization of the
      lesion in WS has been known for a long time, but there are no studies on the
      possible correlation between lesion topography and neurophysiological deficit.
      Assuming that afferents from the three branches of the trigeminal nerve reach
      different parts of the trigeminal nuclei, we examined the possible correlation
      between the lesion topography assessed by the MRI and the neurophysiological
      deficit, assessed by studying the brain stem reflexes in patients with WS within
      2 weeks after stroke. Neurophysiological abnormalities were always located in the
      afferent branch of the reflexes examined, but not all patients exhibited
      abnormalities in all responses. The ophthalmic branch was involved in 92.8% of
      patients, and the mandibular branch in 57.1% of patients. The patients with MRI
      lesions located in the lower medulla had normal responses with infraorbital or
      mental nerve stimulation. The results of this neurophysiological study confirm
      the heterogeneity of WS. Whether the neurophysiological identification of
      different subgoups of patients is relevant for clinical outcome needs further
      studies.

PMID- 8761265
TI  - Properties of sprouted rat motor units: effects of period of enlargement and
      activity level.
AB  - The effects of short and prolonged partial denervation of lateral gastrocnemius
      muscles in sedentary and active rats (running) were examined. In PD muscles of
      sedentary animals the mean motor unit (MU) tetanic force after 30 days was not
      different than that measured after 90 days. Increased locomotor activity over the
      same period (voluntary running, approximately equal to 6 km/day) resulted in an
      increase in mean MU tetanic force of enlarged MUs (28%). The absence of a
      significant increase in mean muscle fiber area suggested an activity-related
      enhancement of motoneuron sprouting. However, the small magnitude of this
      increase, relative to the potential for further sprouting, indicates the activity
      effect is not strong and may be partly due to fiber area changes not evident with
      whole muscle analysis. Nonetheless, these data demonstrate that daily locomotor
      activity can enhance the tension-generating capacity of chronically enlarged MUs.

PMID- 8761266
TI  - Effects of femoral nerve stimulation on the electromyogram and reflex
      excitability of tibialis anterior and soleus.
AB  - The present study was undertaken to determine whether femoral nerve stimulation
      would produce heteronymous reflex responses in tibialis anterior (TA) and soleus,
      demonstrable by averaging the electromyogram (EMG) produced by a voluntary
      contraction, and whether the responsible changes in excitability were sufficient
      to affect the H reflexes of TA and soleus. In both muscles, femoral stimuli
      produced short-latency, presumably monosynaptic excitation, better defined in
      poststimulus averages of unrectified EMG, followed by long-lasting inhibition,
      better defined in averaged rectified traces. The H reflexes underwent changes at
      appropriate latencies. The thresholds for excitation and inhibition were,
      respectively, below and above threshold for the quadriceps M wave. The
      heteronymous responses were largely independent of stimulus rate and, within
      limits, scaled with the level of background contraction. The ability to define
      these heteronymous connections using relatively simple methodology extends their
      utility. Such tests may prove useful in probing pathophysiological mechanisms in
      individual patients.

PMID- 8761267
TI  - Single channel evidence for a cytoskeletal defect involving acetylcholine
      receptors and calcium influx in cultured dystrophic (mdx) myotubes.
AB  - Single channel events that exhibited the conductance, event duration, and ion
      selectivity characteristics of calcium leakage activity (CLA) were recorded in
      association with acetylcholine receptor (AChR) activity in cultured nondystrophic
      myotubes. The CLA was observed in the presence or absence of acetylcholine (ACh),
      and at normal or elevated concentrations of calcium. In contrast to results from
      nondystrophic myotubes, cell-attached patches from several cultured dystrophic
      (mdx) myotubes exhibited 100% CLA with no AChR activity, even though ACh was
      present in the pipette solution. Acquisition of an inside-out patch from these
      membrane areas produced a profound decrease in CLA and the appearance of AChR
      events exhibiting typical conductance and event duration characteristics. These
      results suggest that CLA in dystrophic muscle is produced, in part, by unusual
      physical interactions between AChRs and the dystrophic cytoskeleton that are
      mediated by the action of intracellular modulators responsible for aggregating
      and stabilizing AChRs.

PMID- 8761268
TI  - Repetitive CMAPs: mechanisms of neural and synaptic genesis.
AB  - Repetitive compound muscle action potentials (R-CMAPs) occur when a single nerve
      shock excites muscle fibers repeatedly. "Double discharges" are due to
      intramuscular nerve reexcitation. "Synaptic" R-CMAPs, due to excess acetylcholine
      in the neuromuscular synapse, can occur in congenital myasthenia, the slow
      channel syndrome, and acetylcholinesterase inhibition. Secondary nerve excitation
      can reexcite muscle fibers. Synaptic R-CMAPs in a patient consisted of two
      discharges. The second diminished during repetitive stimulation and began 3.5-4.0
      ms after the first, which is slightly longer than the synapse-muscle refractory
      period. Neural R-CMAPs, due to ectopic nerve activity, occur in neuromyotonia
      (NMT). R-CMAPs in a patient consisted of about 20 discharges at 200-300 Hz.
      Studies in healthy subjects showed that such trains represent added single CMAPs.
      Impulse frequency in the patient lied close to the threshold of refractoriness.
      Refractoriness of the synapse-muscle cell assembly determines the characteristics
      of R-CMAPs regardless of the primary cause.

PMID- 8761269
TI  - Molecular basis of muscle phosphoglycerate mutase (PGAM-M) deficiency in the
      Italian kindred.
AB  - Human muscle phosphoglycerate mutase (PGAM-M) deficiency is associated with
      exercise intolerance, muscle cramps, chronic serum CK elevation, and recurrent
      episodes of myoglobinuria. Ten patients have been described: 7 African Americans,
      1 African, and 2 Caucasians from the Italian kindred described here. Molecular
      genetic analysis has revealed three different mutations in the PGAM-M gene. The
      propositus of the Italian family was homozygous for a unique point mutation at
      codon 90 in exon 1, a C-to-T transition converting an encoded arginine to
      tryptophan. His sister, who had similar complaints, was also homozygous for this
      mutation while the paternal grandfather, both parents, a brother and a nephew of
      the propositus were heterozygous for the mutation. Our studies exclude that PGAM
      M deficiency is limited to African Americans, and suggest that the molecular
      heterogeneity of this rare disorder may be due to a "founder effect" in different
      ethnic groups.

PMID- 8761270
TI  - Abductor hallucis false motor points: electrophysiologic mapping and cadaveric
      dissection.
AB  - False motor points (FMPs) can occur in intrinsic foot or hand muscles, causing
      spuriously prolonged distal motor latencies by misrepresenting the compound
      muscle action potential (CMAP) onset. We investigated the motor point (MP) and
      possible FMPs in abductor hallucis (AH) by three methods: (1) electrophysiologic
      mapping of the CMAP with a grid of approximately 29 G1 sites over AH (n = 20),
      including commonly used MPs just anterior to (Ant-MP) and posterior to (Post-MP)
      the navicular tuberosity; (2) electrophysiologic mapping with direct percutaneous
      threshold stimulation of AH (same grid as above); and (3) cadaveric dissection (n
      = 4). We found AH FMPs in 19 of 20 feet (2.7 FMPs/foot) which resulted in
      prolongation of the CMAP onset latency by 0.5-2.3 ms. Post-MP had a significantly
      lower mean threshold stimulus intensity than all other grid sites, including the
      FMPs. The anatomic MP of AH was consistently found just inferior and posterior to
      the navicular tuberosity. This study demonstrates that AH FMPs: (1) can be
      identified in virtually all feet; (2) do not correspond to the true MP (i.e.,
      Post-MP); and (3) are likely due to superimposed compound action potentials from
      nearby muscles or nerves.

PMID- 8761271
TI  - Elevated levels of complement components C5 and C9 and decreased antitrypsin
      activity in the serum of patients with X-linked vacuolated myopathy.
AB  - We have recently reported a French family presenting with an X-linked vacuolated
      myopathy. Here we show that levels of complement components C5 and C9 are
      elevated in the serum of these patients. Moreover, antitrypsin activity is
      decreased in the serum of the patients. Taken with the deposition of membrane
      attack complex encountered in muscle tissue, these results emphasize the role of
      complement in the pathogenesis of this rare muscular disorder.

PMID- 8761272
TI  - Mobius syndrome: electrophysiologic studies in seven cases.
AB  - Mobius syndrome is characterized by congenital facial diplegia, frequent
      impairment of gaze, variable involvement of other cranial muscles, and various
      musculoskeletal anomalies. The site of dysfunction remains debatable. We
      performed detailed electrophysiologic studies in 5 children and 2 adults with
      Mobius syndrome to better delineate the pathophysiology of this disorder. Sensory
      and motor conduction studies were normal in the extremities. Facial compound
      muscle action potential amplitudes were reduced in all patients. The blink reflex
      R1 responses were unobtainable unilaterally in 2 patients and unobtainable
      bilaterally in 3 patients. Otherwise, R1 and R2 latencies were variably
      prolonged. The jaw jerk and masseter silent periods, tested in 2 patients, were
      normal. Detailed electromyographic studies of facial muscles revealed multifocal,
      chronic neurogenic changes. The findings indicate a brain stem process
      predominantly affecting the facial nuclei and their internuclear connections
      rather than a supranuclear or muscular site of involvement.

PMID- 8761273
TI  - Duchenne phenotype with in-frame deletion removing major portion of dystrophin
      rod: threshold effect for deletion size?
AB  - In a 9-year-old boy with Duchenne muscular dystrophy we found a large in-frame
      deletion, spanning exons 10 to 53 of the dystrophin gene. The deletion removed
      almost all of the central rod domain of dystrophin. Using carboxyterminal
      dystrophin antibodies the immunohistochemical reaction was normal in all muscle
      fibers. In immunoblot studies we found dystrophin of abnormal size (160 kDa) and
      normal amount (about 100%). The immunochemical features and the reading frame
      deduced from DNA analysis are usually associated with Becker muscular dystrophy,
      but the clinical characteristics were those of the severe Duchenne phenotype. All
      the cases of in-frame dystrophin deletions reported so far, which involved more
      than 36 exons, invariably resulted in a severe phenotype. Therefore, a threshold
      effect for dystrophin length may be reasonably suspected. Very short dystrophin
      molecules might induce a severe disarray of the dystrophin network.

PMID- 8761274
TI  - Isolated vitamin E deficiency.
AB  - A 22-year-old man presented with progressive gait instability, tremor, and
      dysarthria since childhood. Electrophysiologic studies revealed a sensorimotor
      polyneuropathy. Laboratory studies documented vitamin E deficiency; however, no
      gastrointestinal, hepatic, or lipoprotein disorder could be identified. Vitamin E
      therapy normalized the serum level, but there was no neurologic improvement.
      Isolated vitamin E deficiency, in the absence of lipid malabsorption, should be
      considered in the evaluation of children and adults with ataxia and peripheral
      neuropathy.

PMID- 8761276
TI  - Nerves and muscles of patients after multipolar sequential phrenic nerve
      stimulation.

PMID- 8761275
TI  - Specificity of autoantibodies react with omega-conotoxin MVIIC-sensitive calcium
      channel in Lambert-Eaton myasthenic syndrome.

PMID- 8761277
TI  - Stimulated single-fiber electromyography in wound botulism.

PMID- 8761278
TI  - Acquired demyelinating polyneuropathy presenting as a pure clinical sensory
      syndrome.

PMID- 8761279
TI  - Treatment with ciliary neurotrophic factor does not improve regeneration in
      experimental autoimmune neuritis of the Lewis rat.

PMID- 8761280
TI  - Neuralgic amyotrophy misdiagnosed as diaphragmatic rupture.

PMID- 8761281
TI  - Nonrandom behavior in a reaction-time time series.

PMID- 8761282
TI  - Acetylcholine receptor antibodies as a marker of treatable fatigue in HIV-1
      infected individuals.

PMID- 8761283
TI  - Fact and fallacy in clinical and electrophysiological studies of anomalous
      innervation of the intrinsic foot muscles.

PMID- 8761284
TI  - Hirschsprung's disease in myotonic dystrophy.

PMID- 8761285
TI  - The mdx mouse: why diaphragm?

PMID- 8761286
TI  - Immunization and risk of relapse of Guillain-Barre syndrome or chronic
      inflammatory demyelinating polyradiculoneuropathy.

PMID- 8761287
TI  - bcl-w, a novel member of the bcl-2 family, promotes cell survival.
AB  - The prototypic mammalian regulator of cell death is bcl-2, the oncogene
      implicated in the development of human follicular lymphoma. Several homologues of
      bcl-2 are now known. Using a PCR-based strategy we cloned a novel member of this
      gene family, denoted bcl-w. The gene, which is highly conserved between mouse and
      human, resides near the T-cell antigen receptor alpha gene within the central
      portion of mouse chromosome 14 and on human chromosome 14 at band q11. Enforced
      expression of bcl-w rendered lymphoid and myeloid cells refractory to several
      (but not all) cytotoxic conditions. Thus, like Bcl-2 and Bcl-x, the Bcl-w protein
      promotes cell survival, in contrast to other close homologues, Bax and Bak, which
      facilitate cell death. Comparison of the expected amino acid sequence of Bcl-w
      with that of these relatives helps to delineate residues likely to convey
      survival or anti-survival function. While expression of bcl-w was uncommon in B
      or T lymphoid cell lines, the mRNA was observed in almost all murine myeloid cell
      lines analysed and in a wide range of tissues. These findings suggest that bcl-w
      participates in the control of apoptosis in multiple cell types. Its functional
      similarity to bcl-2 also makes it an attractive candidate proto-oncogene.

PMID- 8761288
TI  - A defined chromosome 6q fragment (at D6S310) harbors a putative tumor suppressor
      gene for breast cancer.
AB  - Recent evidence obtained by cytogenetic and molecular studies indicates that in
      breast cancer chromosome 6q is often affected by genetic changes suggesting the
      existence of putative tumor suppressor genes (TSGs). However the function of
      gene(s) on this chromosome in breast cancer suppression is not understood. To
      substantiate further the presence of breast cancer related TSGs at 6q and to
      define their location, we first performed microcell-mediated transfer of
      chromosome 6 to CAL51 breast cancer cells for studying possible suppression of
      malignant phenotype and secondly, we analysed DNAs from 46 primary breast cancers
      for loss of constitutive heterozygosity (LOH) using 24 poly-morphic
      microsatellite markers. The chromosome transfer resulted in loss of
      tumorigenicity and reversion of other neoplastic properties of the microcell
      hybrids. Polymorphism analysis of single hybrids revealed that they harbored only
      a small donor chromosome fragment defined by the marker D6S310 (6q23.3-q25) and
      flanked by D6S292 and D6S311. The LOH data suggest that four tumor suppressor
      gene loci mapped to the central and distal portion of 6q may be independently
      deleted in breast cancer. One of these regions corresponds to the region
      identified by chromosome transfer.

PMID- 8761289
TI  - Prevalence of mutations of ras and p53 in benign and malignant thyroid tumors
      from children exposed to radiation after the Chernobyl nuclear accident.
AB  - Starting 4 years after the Chernobyl accident, a dramatic increase in incidence
      of thyroid carcinoma was noticed in children from contaminated areas. The
      incidence of benign thyroid lesions in the exposed population was also increased.
      To study the possible role of ras and p53 genes in radiation-induced thyroid
      tumorigenesis, 33 papillary carcinomas, one follicular carcinoma and 22 benign
      lesions removed from children aged 5-19 were screened for point mutations of H-,
      K-, and N-ras, as well as of p53 (exons 5-8) using single strand conformation
      polymorphism (SSCP) analysis. Ras point mutations were detected in 1/1 case of
      follicular carcinoma (N-ras codon 61 CAAgln-->AAAlys), and in 3/7 follicular
      adenomas (N-ras codon 61 CAAgln-->CGAarg x 2, CAAgln-->AAAlys). None of the cases
      of papillary thyroid carcinoma was positive for ras oncogene abnormalities. The
      lack of K-ras mutations was confirmed by allele-specific oligonucleotide
      hybridization (ASOH), and by sequencing in five cases. Somatic point mutations in
      p53 were found by SSCP in 2/33 papillary thyroid carcinomas, with one missense
      mutation (exon 5, codon 160 ATGmet-->GTGval) and another silent mutation (codon
      182, TGCcys-->TGTcys). Immunohisto-chemically, focally positive p53 staining was
      found in four papillary carcinomas being primarily confined to solid and poorly
      differentiated areas in tumors. These data demonstrate that as opposed to the few
      reports on tumors arising after therapeutic external irradiation, ras mutations
      are not primary events in the development of post-Chernobyl thyroid papillary
      carcinomas. p53 mutations do not appear to be important in the development of
      these tumors, but may in some cases have a role in progression to a more
      aggressive phenotype that has not yet fully manifested in these pediatric
      neoplasms.

PMID- 8761290
TI  - Endoreplication in megakaryoblastic cell lines is accompanied by sustained
      expression of G1/S cyclins and downregulation of cdc25C.
AB  - In most eukaryotic cells, a link between S and M phases of the cell cycle must be
      assured in order to maintain the ploidy of newly divided cells. However, in some
      cell l/pes, e.g. the precursors of platelets megakaryocytes, extra S-phases can
      occur in the absence of concomitant mitoses, resulting in polyploidy. We have
      used two established cell lines with megakaryoblastic characteristics (HEL and
      MEG-01) to investigate the molecular events that lead these cells to bypass the
      regular control checkpoints that govern the interdependency of S and M phases. In
      the presence of the phorbol ester TPA, both cell lines stopped proliferating and
      displayed additional megakaryocytic features, including polyploidization.
      Analysis of key cell cycle regulatory factors implicated in the control of G1/S
      and G2/M transitions revealed a number of differences compared to normally
      cycling cells. Differentiating megakaryocytes were found to maintain high levels
      of cdk2, and cyclins E and A. This was accompanied by the appearance of the
      retinoblastoma protein in the hyperphosphorylated, functionally inactivated form.
      In addition, TPA-treated cells showed high levels of cyclin B and cdc2 proteins,
      however no activation of cdc2 was detected. This lack of cdc2 activation which
      should occur for entry into M phase appeared to be related to the down regulation
      of cdc25C phosphatase found in both differentiated HEL and MEG-01 cells.
      Together, our results suggest that in differentiating megakaryoblastic cells
      endoreplication is accompanied by sustained levels of cyclins A and E, and a lack
      of cdc2 activation, which is probably mediated through down regulation of cdc25C
      protein phosphatase.

PMID- 8761291
TI  - Alternatively spliced cyclin C mRNA is widely expressed, cell cycle regulated,
      and encodes a truncated cyclin box.
AB  - The cyclin C protein has recently been shown to associate with a unique cyclin
      dependent protein kinase (cdk8) and it has been proposed that this complex may
      regulate RNA transcription during the cell cycle. In addition, the human cyclin C
      gene has been localized to human chromosome 6q21 and it was found to be
      frequently deleted in a subset of acute lymphoblastic leukemias (ALL's).
      Screening of an avian T-cell cDNA library resulted in the isolation of a cyclin C
      homologue as well as an abundant, yet distinct, cyclin C-related cDNA. The
      predicted open reading frame (ORF) of the cyclin C cDNA predicted a 283 amino
      acid protein that was > 99% identical to the human protein and 72% identical to
      the Drosophila melanogaster protein. However, the predicted ORF of the cyclin C
      related cDNA predicted a much smaller 105 amino acid protein that was identical
      to cyclin C well into the cyclin-box region (amino acid residue 98), where it
      abruptly diverges and then terminates. Using PCR analysis of cDNA derived from a
      range of cell lines and tissues, alternative splicing of the avian cyclin C gene
      has been demonstrated. Furthermore, a smaller approximately 19 kDa protein that
      co-migrates with the in vitro transcribed and translated truncated cyclin C
      protein was detected in normal and virally-transformed avian cells with a cyclin
      C-specific antibody. Expression of alternatively spliced cyclin C mRNA and
      protein is regulated in a cell cycle-dependent manner reminiscent of cyclin B2.
      The function of this truncated cyclin C protein is not known, but its expression
      in avian cells suggest that this truncated cyclin C protein may participate as an
      early endogenously encoded cyclin C inhibitor.

PMID- 8761292
TI  - Hydrogen peroxide induces complex formation of SHC-Grb2-SOS with receptor
      tyrosine kinase and activates Ras and extracellular signal-regulated protein
      kinases group of mitogen-activated protein kinases.
AB  - Protein tyrosine phosphorylation events play determinant roles in cellular
      processes such as proliferation and differentiation. We have recently reported
      that hydrogen peroxide, an active oxygen species and a cellular oxidant,
      stimulates growth response events in vascular smooth muscle cells (VSMC). To
      understand the mechanisms by which oxidant stress modulates these growth response
      events, we have studied the effect of hydrogen peroxide on protein tyrosine
      phosphorylation events in VSMC. Our findings show that hydrogen peroxide
      stimulates tyrosine phosphorylation of several proteins including epidermal
      growth factor receptor (EGFR) in VSMC. Hydrogen peroxide-induced tyrosine
      phosphorylation of EGFR was found to be time dependent; with a threefold increase
      at 5 min and a 20-fold increase at 30 min of treatment as compared to control
      levels. Hydrogen peroxide treatment of VSMC also resulted in a time-dependent
      increase in tyrosine phosphorylation of SHC proteins. In addition, hydrogen
      peroxide-induced tyrosine-phosphorylated EGFR formed a complex with SHC-Grb2-SOS.
      These events were followed by activation of Ras and extracellular signal
      regulated protein kinases (ERKs) group of mitogen-activated protein kinases
      (MAPKs). Together these findings demonstrate for the first time that hydrogen
      peroxide, a cellular oxidant, possess the ability to activate EGFR-mediated
      signaling events in VSMC. These EGFR-mediated signaling events may be important
      in oxidant stress-induced cellular responses.

PMID- 8761293
TI  - Broadly expressed SNT-like proteins link FGF receptor stimulation to activators
      of Ras.
AB  - SNT was originally described as a approximately 90 kilodalton protein in neuronal
      precursor cells which bears affinity for the yeast cell cycle protein p13sucl and
      which undergoes rapid tyrosine phosphorylation following stimulation with growth
      factors which trigger terminal differentiation, but not by other growth factors
      which promote proliferation (Rabin et al., 1993). We show here that similarly
      sized SNT-like proteins (SLPs) are expressed in fibroblast, myoblast, and
      lymphoid cell lines, and undergo robust tyrosine phosphorylation in response to
      several mitogenic ligands, including fibroblast growth factors (FGFs). SLPs are
      tyrosine phosphorylated within 15 s of FGF stimulation, are predominantly
      membrane-associated, and are weakly associated with activated FGF receptor-1,
      suggesting that these proteins may be direct targets of the receptor kinase.
      Kinetic analysis of SLP phosphorylation and studies with serine/threonine kinase
      and phosphatase inhibitors suggest that SLPs are no larger than 70 000
      kilodaltons, and that serine/threonine phosphorylation follows tyrosine
      phosphorylation to substantially retard gel electrophoretic mobility. SLPs are
      associated with the Grb-2 adaptor and are the major tyrosine phosphorylated
      proteins associated with the Ras guanine nucleotide exchange factor Sos in FGF
      stimulated fibroblasts, suggesting that SLP-Grb2-Sos complexes modulate the
      activity of Ras proteins.

PMID- 8761294
TI  - Expression of an ATP binding mutant of PKC-delta inhibits Sis-induced
      transformation of NIH3T3 cells.
AB  - In an effort to determine the role of protein kinase C-delta (PKC-delta) in
      cellular transformation mediated by the sis proto-oncogene, we cotransfected
      expression vectors containing cDNAs that encode for c-sis with an ATP binding
      mutant of PKC-delta (PKC-delta K376R) or wild type PKC-delta (PKC-delta WT) into
      NIH3T3 cells. Our results showed that expression of PKC-delta K376R severely
      impaired Sis-induced focus formation, whereas cotransfection of PKC-delta WT cDNA
      had no effect on Sis-mediated transformation. Consistent with this result, PKC
      delta K376R expression also inhibited PDGF-BB-mediated anchorage-independent
      colony formation. While cotransfection of a vector containing a dominant negative
      mutant of ras (N17 ras) cDNA potently inhibited Sis-induced transformation, the
      expression of PKC-delta K376R did not block transformation mediated by v-H-Ras or
      v-Raf. In addition, PDGF-BB-induced Raf and mitogen-activated protein kinase
      activation, which are known to be downstream molecules in the Ras cascade, were
      not affected by the expression of PKC-delta K376R, indicating that PKC-delta and
      Ras are segregated in mediating Sis-induced transformation. Interestingly,
      expression of PKC-delta K376R strongly reduced TPA responsive element (TRE)
      transactivation induced by PDGF stimulation, suggesting that activation of TRE
      containing genes, which may be involved in Sis-mediated transformation, are
      negatively regulated by expression of PKC-delta K376R.

PMID- 8761295
TI  - Induction of apoptosis by tamoxifen-activation of a p53-estrogen receptor fusion
      protein expressed in E1A and T24 H-ras transformed p53-/- mouse embryo
      fibroblasts.
AB  - A fusion gene consisting of wild-type p53 linked to a modified ligand binding
      domain of the murine estrogen receptor has been constructed and should be a
      useful tool for studying controlled activation of wild-type p53 function in a
      variety of experimental cell systems. The protein product of this gene, p53ERTM,
      is expressed in cells constitutively but is not functional unless associated with
      tamoxifen or 4-hydroxytamoxifen. p53ERTM was introduced into p53-deficient mouse
      embryo fibroblasts (MEFs) expressing the E1A and T24 H-ras oncogenes. Activation
      of p53 in these transformed cells by the addition of tamoxifen or 4
      hydroxytamoxifen resulted in apoptosis. In addition to engaging the apoptotic
      machinery, the tamoxifen-activated fusion protein exhibited other functions
      characteristic of wild-type p53, such as induction of WAF1 and MDM2 gene
      expression and activation of the p53-dependent spindle checkpoint in cells
      treated with nocodazole. Activation of p53ERTM expressed in p53-positive MEFs
      coexpressing E1A and ras had, at most, only a small cytotoxic effect. When three
      cell lines of transformed p53+/+ fibroblasts not expressing p53ERTM were tested
      for sensitivity to the DNA-damaging drug doxorubicin, the p53+/+ clones displayed
      either comparable sensitivity, or at most an increase in drug sensitivity of less
      than fourfold, as compared to several p53-/- cell lines. Our data show that
      restoration of wild-type p53 activity is sufficient to trigger apoptosis in p53-/
      MEFs transformed with E1A and T24 H-ras and suggest that rare propagable clones
      of p53-normal MEFs expressing the E1A and T24 H-ras oncogenes have suffered
      compensatory alterations that compromise the ability to undergo p53-dependent
      apoptosis.

PMID- 8761297
TI  - Cooperation of TGF alpha and c-Myc in mouse mammary tumorigenesis: coordinated
      stimulation of growth and suppression of apoptosis.
AB  - We have previously shown that TGF alpha and c-Myc interact in a strong,
      synergistic fashion to induce mammary gland tumors in double transgenic mice.
      Here we show this interaction can be explained, at least in part, by a
      cooperative growth stimulus by the two proteins, and by TGF alpha-mediated
      inhibition of c-Myc-induced apoptosis. We initially compared rapidly progressing
      mammary tumors from double transgenic mice to long latency tumors from single
      transgenic mice and observed a striking difference in the occurrence of apoptosis
      among the three groups. Tumors exhibiting apoptosis were derived exclusively from
      mice that expressed the c-myc transgene in the absence of the TGF alpha
      transgene, indicating that TGF alpha might protect c-Myc-overexpressing cells
      from programmed cell death. Cell lines were derived from single and double
      transgenic mammary tumors to examine further the mechanism underlying the
      cooperative interaction between the two gene products. In accordance with our in
      vivo data, apoptosis was only detected when the c-myc transgene was expressed
      without the TGF alpha transgene. Furthermore, exogenous addition of TGF alpha
      inhibited apoptosis in cells overexpressing c-Myc alone. In addition, tumor
      derived cells that overexpressed both TGF alpha and c-Myc exhibited faster growth
      rates in vitro and in vivo and were less sensitive to the inhibitory effects of
      TGF beta in vitro compared to cell lines expressing only one of the transgenes.
      Based on our findings we propose that TGF alpha acts both as a proliferative and
      a survival factor for c-Myc-expressing tumor cells. Our results indicate that TGF
      alpha and c-Myc cooperate in tumorigenesis via a dual mechanism: TGF alpha can
      inhibit c-Myc-induced apoptosis and both proteins provide a growth stimulus.

PMID- 8761296
TI  - Molecular characterization of mouse and rat CPP32 beta gene encoding a cysteine
      protease resembling interleukin-1 beta converting enzyme and CED-3.
AB  - Interleukin-1 beta converting enzyme (ICE) defines a new class of mammalian
      cysteine protease that shares strong homology with the Caenorhabditis elegans
      death gene ced-3. Both ICE and CED-3, when introduced into cultured cells, induce
      apoptosis, indicating that this type of cysteine protease may play an important
      role in the process of programmed cell death. Here, we report the cloning of a
      mouse and rat gene encoding a novel cysteine protease. The putative proteins
      encoded by these cDNAs contain the conserved sequence (QACRG) necessary for
      covalent linkage to the substrate as well as the three amino acids responsible
      for substrate binding and catalysis in ICE. Amino acid sequence analysis
      indicates that this rodent cysteine protease is the homolog of human CPP32 beta.
      Mouse CPP32 beta mRNA is highly expressed in spleen, and to a lesser degree in
      brain, lung, liver, and kidney. The mouse CPP32 beta genomic locus spans a region
      of approximately 20 kb, including seven exons and six introns. Mouse
      interspecific backcross mapping allowed localization of CPP32 beta to the central
      region of mouse chromosome 8, linked to Scvr, Lpl, Jund1 and Mlr.

PMID- 8761298
TI  - The aminoterminal phosphotyrosine binding domain of Shc associates with ZAP-70
      and mediates TCR dependent gene activation.
AB  - T-cell antigen receptor stimulation results in recruitment to the zeta chain and
      phosphorylation both of the syk family protein tyrosine kinase ZAP-70 and of the
      Shc adaptor protein, which transduces activating signals to Ras. Both ZAP-70 and
      Ras are required for T-cell activation. We have investigated the functional link
      between these two molecules in TCR signaling. She was found to associate with ZAP
      70 in response to TCR triggering. This association was dependent on the presence
      of the aminoterminal phosphotyrosine binding (PTB) domain of She. The analysis of
      She binding to a potential PTB domain binding site on ZAP-70 confirmed the
      interaction of the She PTB domain with ZAP-70 and identified the ZAP-70
      phosphotyrosine residue involved in this interaction. To test the role of the She
      PTB domain in transducing TCR derived signals we measured the effects of the
      isolated She PTB domain on the activation of the T-cell specific transcription
      factor NF-AT. The isolated She PTB domain was designed to compete non
      productively with endogenous She for binding to up-stream tyrosine phosphorylated
      proteins and thus interfere with coupling to regulators of Ras activation. A
      significant inhibition of NF-AT activation by TCR triggering was observed,
      showing a functional involvement of She in TCR signaling through its PTB domain
      and suggesting an important role for She association with ZAP-70.

PMID- 8761299
TI  - A new member of the Eph family of receptors that lacks protein tyrosine kinase
      activity.
AB  - Using a PCR-based screen to identify tyrosine kinases involved in T cell
      development, we have cloned a new member of the Eph-family of receptor tyrosine
      kinases (Mep, for murine eph-family protein). At the amino acid level Mep is 60%
      identical to the chicken embryonic kinase Cek9. Sequence analysis indicates that
      the predicted extracellular portion of Mep bears an Ig-like domain, a cysteine
      rich region, and sequences homologous to fibronectin type III. The transmembrane
      region of Mep is followed by a kinase domain. Surprisingly, this kinase domain
      carries amino acid substitutions in the highly conserved consensus motifs found
      in all protein tyrosine kinases and known to be crucial for kinase activity. We
      demonstrate that a bacterial fusion protein of the Mep kinase domain does not
      have protein tyrosine kinase activity. Analysis of Mep mRNA levels in a variety
      of mouse tissues shows that Mep is highly expressed in thymus and brain. We have
      also isolated two additional Mep cDNA clones from thymocytes which are predicted
      to encode secreted forms of the Mep extracellular domain; mRNAs encoding these
      secreted isoforms are also expressed in mouse brain.

PMID- 8761300
TI  - The deleted in colon cancer (DCC) gene is consistently expressed in colorectal
      cancers and metastases.
AB  - The DCC (deleted in colorectal cancer) gene was originally identified as a
      candidate tumour suppressor gene in colon carcinogenesis on the basis of allelic
      losses in chromosome 18q.21 in 70% of colon cancers. Reverse transcriptase
      polymerase chain reaction (RT-PCR) of DCC mRNA suggests that DCC expression may
      also be reduced in colon cancers. We have used monoclonal antibodies generated
      against the DCC immunoglobulin-like domain to investigate DCC isoforms and DCC
      protein expression during colon cancer progression. Normal mucosa and colonic
      tumour specimens representative of the range of colonic tumour progression from
      benign adenomatous polyps to metastases were compared by Western blot analyses.
      We show that while M(r) 194 000 DCC is present in normal colonic mucosa and
      adenomatous polyps, it is also similarly expressed in colorectal carcinomas and
      colonic metastases in the liver. The presence of DCC protein is consistent with
      the presence of DCC mRNA transcripts in the same tissue specimens. Notably DCC
      was not completely lost in any colonic tumour specimens examined, even those that
      had progressed to metastatic cancers. Quantitation of DCC protein expression in
      tissue specimens by densitometry demonstrated that both normal and malignant
      specimens exhibit a wide range of DCC protein levels and there was no significant
      correlation between diminished DCC protein expression and colon cancer
      progression. These results demonstrate the pattern of expression of the DCC gene
      product in colonic tumour progression and show that absence of DCC expression is
      not associated with colonic tumour progression.

PMID- 8761301
TI  - Characterization of t(11;14) translocation in mantle cell lymphoma by fluorescent
      in situ hybridization.
AB  - Characterization of chromosome abnormalities in leukemia and lymphoma have
      contributed to the understanding of the molecular basis of these neoplastic
      diseases. In addition, specific chromosomal aberrations have acquired diagnostic
      or prognostic value. The t(11;14)(q13;q32) chromosome translocation has been
      detected in mantle cell lymphomas. However, possibly due to the limits of
      conventional cytogenetic analysis and the presence of different breakpoints at
      the molecular level, it is possible that the true percentage of association is
      underestimated. In our study, we used a yeast artificial chromosome, spanning the
      entire area where the rearrangements occur on chromosome 11q13, to detect the
      presence of translocations by fluorescent in situ hybridization experiments. We
      detected BCL-1 translocations in eight of eight patients with clinical and
      immunological features of mantle cell lymphoma, suggesting that the t(11;14)
      translocation is a critical event in the pathogenesis of MCL and may be a primary
      element for the diagnosis. Since this translocation is associated with poor
      prognosis, its detection may help to make a correct diagnosis as well as to
      evaluate residual disease, which is critical to plan a rational chemotherapy
      regimen.

PMID- 8761302
TI  - Conditional expression of N-myc in human neuroblastoma cells increases expression
      of alpha-prothymosin and ornithine decarboxylase and accelerates progression into
      S-phase early after mitogenic stimulation of quiescent cells.
AB  - To elucidate the contribution of the N-Myc protein to neuroblastomas we have used
      a synthetic inducible expression system on the basis of the tetracycline
      repressor of E coli to reversibly express N-myc in a human neuroblastoma cell
      line in which expression of endogenous N-myc is barely detectable. Like the c-Myc
      protein, N-Myc up-regulates the expression of both alpha-prothymosin and
      ornithine decarboxylase. Induction of N-myc increases both the rate of DNA
      synthesis and the proliferation rate, and shortens the G1 phase of the cell
      cycle. A comparison of cell populations in which the presence of N-Myc protein
      was restricted to different parts of G(zero)/G1 revealed that N-Myc is rate
      limiting for cell cycle progression during the first 5 h after serum stimulation
      of quiescent cells providing direct evidence that Myc-proteins act early after
      mitogenic stimulation of quiescent cells.

PMID- 8761303
TI  - Characterization of a ligand for receptor protein-tyrosine kinase HTK expressed
      in immature hematopoietic cells.
AB  - HTK is a receptor tyrosine kinase that belongs to the Eph subfamily. An extensive
      screening using BIAcore system revealed that a colon cancer cell line, C-1,
      expressed the ligand for HTK. From the conditioned medium of C-1 cells, a soluble
      form of ligand was purified by receptor affinity chromatography, and the
      isolation of full-length cDNA revealed that this ligand is identical to the human
      HTK ligand (HTKL) previously reported. HTK receptor tyrosine phosphorylation was
      induced by membrane-bound or clustered soluble HTKL but not by unclustered
      soluble HTKL, indicating that HTKL requires cell-to-cell interaction for receptor
      activation. Binding analysis demonstrated that HTKL binds to HTK with a much
      higher affinity (Kd: 1.23 nM) than the other transmembrane-type ligand for Eph
      family, LERK-2/ELKL (Kd: 135 nM). The expression of HTK in cord blood cells was
      upregulated after the culture in the presence of stem cell factor. Clustered
      soluble HTKL stimulated the proliferation of sorted HTK+ cord blood cells and a
      hematopoietic cell line, UT-7/EPO from which HTK was isolated. These findings
      suggest the involvement of HTK-HTKL system in the proliferation of HTK+
      hematopoietic progenitor cells in the hematopoietic environment.

PMID- 8761304
TI  - Blockage of RNA polymerase as a possible trigger for u.v. light-induced
      apoptosis.
AB  - To study the triggering mechanism(s) of the induction of apoptosis following
      exposure to u.v. light, we used a genetic approach involving cell strains derived
      from patients with inherited deficiencies in nucleotide excision repair. It was
      found that cells from patients with Cockayne's syndrome, which are deficient in
      the processing of u.v.-induced pyrimidine dimers from the transcribed DNA strand,
      are induced to undergo apoptosis at much lower doses of u.v. light than cells
      with proficient strand-specific repair. The induction of apoptosis correlated to
      the induction of p53 and to the inhibition of total RNA and poly(A) mRNA
      synthesis. We also show that active p53 proteins accumulate following u.v.
      irradiation without any apparent requirement for DNA strand breaks or excision
      repair intermediates. We propose that the blockage of RNA polymerases at DNA
      lesions in the transcribed strand triggers the induction of a pathway leading to
      apoptosis. These findings may help explain a long standing enigma of why, despite
      the DNA repair deficiency, patients with Cockayne's syndrome do not experience an
      elevated risk for skin cancer since potentially pre-mutagenic cells are
      eliminated by an easily triggered apoptotic pathway.

PMID- 8761305
TI  - E1A oncogene expression in target cells induces cytolytic susceptibility at a
      post-recognition stage in the interaction with killer lymphocytes.
AB  - E1A oncogene expression increases the susceptibility of cells from several
      species to lysis by natural killer lymphocytes (NK cells). We asked whether this
      E1A-induced cellular phenotypic conversion is specific for NK cell recognition
      interactions with target cells or whether it results from an E1A effect that is
      mediated independently of recognition. E1A-positive and E1A-negative cell pairs
      were compared for cytolytic susceptibility to other types of killer cells that
      use recognition mechanisms different from those of NK cells. E1A-positive, NK
      susceptible target cells were also preferentially lysed by cytotoxic T
      lymphocytes (CTL) that recognize only foreign MHC molecules, lymphokine-activated
      T cells that lack recognition specificity, and CTL whose conventional recognition
      mechanisms were bypassed by lectin treatment of target cells. E1A expression
      increased cellular susceptibility to both major mechanisms of killer cell lysis
      perforin/granzyme lysis and Fas-dependent lysis. Furthermore, anti-Fas antibody
      lysed E1A-positive, but not E1A-negative, cells expressing comparable levels of
      cell surface Fas antigen. These results indicate that a major mechanism by which
      E1A induces cellular susceptibility to lysis involves a stage in the interaction
      of killer cells with their targets that follows and is independent of cell
      surface recognition.

PMID- 8761306
TI  - The oncoprotein P75gag-v-erbA represses thyroid hormone induced transcription
      only via response elements containing palindromic half-sites.
AB  - The v-erbA oncoprotein P75gag-v-erbA, derived from the thyroid hormone receptor
      alpha (TR alpha), functions as a transdominant transcriptional repressor. The
      mechanism by which P75gag-v-erbA acts is however poorly characterized. Here, we
      show that repression of TR alpha mediated transcription by P75gag-v-erbA in
      transformed erythroblasts is dependent on the structure of the thyroid hormone
      response element to which it binds. A very efficient repression was seen with
      hormone response elements having half-sites organized as everted repeats (ER),
      whereas repression was inefficient with directly repeated half-sites (DR).
      Promoters containing half-sites organized as an inverted palindrome (IR) gave an
      intermediate repression. Although P75gag-v-erbA failed to associate with the
      ligand binding domain of retinoid X (RXR) receptor in a two-hybrid test, the
      oncoprotein in nuclear extracts from transformed cells heterodimerised
      quantitatively with RXR upon binding to response elements of the DR type. On the
      other hand, both RXR/P75gag-v-erb heterodimers and other types of dimers formed
      on ER elements. P75gag-v-erbA also failed to bind to elements that contained only
      one half-site in vivo and in vitro. The data demonstrate that P75gag-v-erbA
      represses gene expression efficiently as a dimer, and suggest that thyroid
      hormone responsive genes that may be targets for the action of the oncoprotein
      are repressed most efficiently if they contain elements of the ER type.

PMID- 8761307
TI  - Autocrine hepatocyte growth factor/scatter factor-Met signaling induces
      transformation and the invasive/metastastic phenotype in C127 cells.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic effector of
      cells expressing the Met tyrosine kinase receptor. C127 is a non-tumorigenic
      mouse cell line which expresses negligible levels of HGF/SF and Met proteins. In
      the present report we have generated C127 cells which overexpress HGF/SF and/or
      Met proteins, and have analysed the effect of HGF/SF-Met signaling in these
      cells. We show that this signaling pathway stimulates the growth and invasiveness
      of C127 cells in vitro and that cells overexpressing both HGF/SF and Met proteins
      (but neither alone) are phenotypically transformed and highly tumorigenic and
      metastatic in vivo. Our data unequivocally demonstrates the autocrine dependency
      of HGF/SF-Met-induced transformation and metastasis in this system and supports
      the theory that the inappropriate expression of HGF/SF and Met proteins could
      play a role in the development and spread of human tumors. In addition, this
      system may be useful for identifying metastasis-associated genes that are
      activated by HGF/SF-Met signaling.

PMID- 8761308
TI  - Functional analysis of the SIS proximal element and its activating factors:
      regulated transcription of the c-SIS/PDGF-B gene in human erythroleukemia cells.
AB  - The SIS proximal element (SPE) is essential for the basal transcription of the c
      sis/PDGF-B gene as well as the lineage-specific, activated transcription of this
      gene seen in megakaryocytes. In gel mobility shift analyses, the SPE element
      forms three gel-shift complexes; the t(op) and b(ottom) complexes were detected
      in nuclear extracts from both untreated and phorbol 12-myristate 13-acetate
      ('tetradecanoylphorbol acetate', TPA) treated K562 cells, whereas the m(iddle)
      complex was detected only in nuclear extracts from TPA-treated K562 cells. Site
      directed mutagenesis of the SPE revealed a CCACCC motif that was essential for
      promoter activity as well as the formation of all three SPE gel-shift complexes.
      Nested-deletion analyses showed that the SPE was required for TPA-inducibility of
      c-sis/PDGF-B transcription. Antibody supershift analyses demonstrated that the t
      gel-shift complex contained both Sp1 and Sp3, and that the b complex contained
      only Sp3. In vitro transcription assays demonstrated that both Sp1 and Sp3 could
      support c-sis/PDGF-B transcription independent of each other in untreated K562
      cells. However, overexpression of Sp1/Sp3 failed to significantly increase the c
      sis/PDGF-B transcription in K562 cells.

PMID- 8761309
TI  - Cloning, expression and chromosomal localization of Wnt-13, a novel member of the
      Wnt gene family.
AB  - The Wnt genes, encoding structurally-related secreted glycoproteins, are
      implicated in mammary carcinogenesis induced by mouse mammary tumor virus. In
      search of the Wnt gene(s) expressed in human gastric cancer, a WTGC1 cDNA
      fragment sharing 66.9% amino-acid homology with human and mouse Wnt-2 was
      isolated by degenerate polymerase chain reaction. The human gene corresponding to
      WTGC1 was designated as Wnt-13 and overlapping Wnt-13 cDNAs were cloned.
      Nucleotide sequence analysis indicated that the Wnt-13 gene encodes the protein
      of 372 amino acids, including a signal peptide, two potential N-glycosylation
      sites and 24 cystein residues highly conserved among members of the Wnt gene
      family. The Wnt-13 mRNA of 2.5 kb in size was detected in heart, brain, placenta,
      lung, prostate, testis, ovary, small intestine and colon of adult human and also
      in brain, lung and kidney of fetal human. Among various cancer cell lines, the
      Wnt-13 mRNA was detected in HeLa (cervical cancer), MKN28 and MKN74 (gastric
      cancer). The Wnt-13 gene has been mapped to human chromosome 1p13. These results
      suggest that the Wnt-13 gene may be involved in normal human development or
      differentiation as well as in human carcinogenesis.

PMID- 8761310
TI  - Phosphorylation of Ets1 regulates the complementation of a CSF-1 receptor
      impaired in mitogenesis.
AB  - Ets1, the founder member of the Ets transcription factor family, is involved in a
      variety of developmental and cellular processes. Previous studies have shown that
      serine phosphorylation of Ets1 inhibits its DNA binding activity, suggesting that
      phosphorylation is important in the regulation of Ets1 function. To further
      examine Ets1 phosphorylation, we ectopically expressed Ets1 in fibroblasts and
      stimulated these cells with serum. Using two-dimensional tryptic phosphopeptide
      analysis and site-directed mutagenesis, we found that Ets1 was phosphorylated on
      threonine 38, a residue conserved in several Ets proteins. Substitution of this
      residue with alanine enhanced CSF-1-dependent colony formation in semi-solid
      medium of NIH3T3 cells expressing a mitogenically defective CSF-1 receptor
      [Y809F]. Threonine 38 is part of a consensus amino-acid sequence frequently
      recognized and targeted by members of the MAP kinase family. Moreover, this
      residue is phosphorylated in vitro by recombinant ERK2, which suggests that the
      kinase which phosphorylates threonine 38 in vivo is a member of the MAP kinase
      family. In addition, phosphorylation on threonine 38 seems to negatively regulate
      Ets1 activity in response to growth-factor stimulation.

PMID- 8761311
TI  - alpha-Tocopherol pretreatment protects the endocrine function of grafts against
      ischemic damage during heterotopic pancreatic transplantation.
AB  - Post-ischemic injury is one of the most important problems affecting successful
      organ procurement and transplantation. The present study was performed to
      determine whether alpha-tocopherol can protect the endocrine function of
      pancreatic grafts against ischemia-reperfusion injury during rat heterotopic
      pancreatic transplantation. Rats with streptozotocin-induced hyperglycemia were
      used as recipients. The donor pancreas was removed and subjected to warm ischemia
      at 37 degrees C for 30, 60, 90 and 120 min, and then transplanted into a
      recipient. A 30-min period of warm ischemia did not impair the endocrine function
      of the pancreatic grafts, which was assessed by measuring the blood glucose
      levels and glucose decay constants (K), and a 60-min period of warm ischemia was
      considered to be the critical period for reversible tissue damage. Pretreatment
      with alpha-tocopherol (20 mg/kg/day, i.v.) for seven days before graftectomy
      significantly decreased blood glucose levels to less than 200 mg/dl and
      significantly increased K values in the recipient rats after transplantation when
      compared with placebo pretreatment. These results suggest that alpha-tocopherol
      pretreatment can protect the endocrine function of pancreatic grafts against
      injury due to warm ischemia followed by reperfusion.

PMID- 8761312
TI  - Synergistic ablation does not affect atrophy or altered myosin heavy chain
      expression in the non-weight bearing soleus muscle.
AB  - The purpose of this study was to investigate whether the soleus muscle undergoes
      atrophy and alterations in myosin heavy chain (MHC) composition during non-weight
      bearing in the absence of synergists. Thirty-two female rats were randomly
      assigned to four groups: control (C), synergistic ablation (ABL) of the
      gastrocnemius and plantaris muscles to overload the soleus muscle, hindlimb
      suspension (HLS), or a combination of synergistic ablation and hindlimb
      suspension (HLS-ABL). After 28 days of hindlimb suspension, soleus atrophy was
      more pronounced in HLS (58%) than in HLS-ABL (43%) rats. Compared to C rats, non
      weight bearing decreased mixed and myofibrillar protein contents and Type I MHC
      49%, 45%, and 7%, respectively, in HLS animals. In addition, de novo expression
      of fast Type IIx and Type IIb MHC (5% and 2%, respectively) was observed in HLS
      animals. Similarly, when compared to C rats, mixed and myofibrillar protein
      contents and Type I MHC decreased 43%, 46%, and 4%, respectively, in HLS-ABL
      animals. Also, de novo expression of Type IIx (4%) and IIb (1%) MHC was observed.
      Collectively, these data indicate that the loss of muscle protein and Type I MHC,
      and the de novo expression of Type IIx and Type IIb MHC in the rat soleus occur
      independently of the presence of synergists during non-weight bearing.
      Furthermore, these results confirm the contention that soleus mass and MHC
      expression are highly sensitive to alterations in mechanical load.

PMID- 8761313
TI  - Major pharmacological distinction of the ACTH receptor from other melanocortin
      receptors.
AB  - The mouse adrenocortical cell line Y1, that expresses ACTH receptors (MC2R), was
      used to probe the binding of ACTH and MSH peptides by using radio-labelled ACTH
      (1-39). The Y1 cells were found to bind [125I]-labelled ACTH (1-39) with high
      affinity (Kd approximately 130 pM). However, none of the melanocortin peptides
      NDP-MSH, alpha-MSH, beta-MSH or gamma 1-MSH could compete with the binding of the
      labelled ACTH(1-39). When other MC receptor subtype DNAs (MC1, MC3 and MC4) were
      transfected into the Y1 cells, characteristic binding of the [125I]NDP-MSH
      appeared for each of the receptor subtype, but no specific binding was present in
      non-transfected cells. This is the first report clearly demonstrating that the
      ACTH receptor binds only ACTH, but not other melanocortin peptides.

PMID- 8761314
TI  - Cell calcium handling and intracellular pH regulation in hereditary
      hypertriglyceridemic rats: reduced platelet response to thrombin stimulation.
AB  - Multiple cell membrane alterations have been described in humans and animals with
      various genetic forms of hypertension and/or dyslipidemia. The aim of our study
      was to characterize some properties of platelets and/or erythrocytes (cytosolic
      calcium handling, intracellular pH regulation and thrombin responsiveness) in a
      new model of genetic hypertension associated with hyperlipidemia-Prague
      hereditary hypertriglyceridemic (HTG) rats. There were no differences in basal
      cytosolic Ca2+ values in platelets or erythrocytes of HTG rats and control Wistar
      rats. Ca2+ influx into erythrocytes was also similar in HTG and control rats. In
      both strains Ca2+ influx correlated positively with plasma triglycerides. The
      slope of this relationship was less steep in HTG than in Wistar rats. Cytosolic
      Ca2+ response to thrombin stimulation was smaller in HTG platelets, which were
      also characterized by a major reduction of thrombin-induced Mn2+ entry through
      receptor-operated Ca2+ channels. Platelets of HTG rats had the same basal
      intracellular pHi values and similar buffering capacity as control rats but their
      pHi response to thrombin stimulation was substantially reduced. It can be
      concluded that reduced responsiveness to thrombin stimulation is a major
      alteration found in platelets of hypertensive hereditary hypertriglyceridemic
      rats.

PMID- 8761315
TI  - Dopamine receptor binding of 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)- 4
      oxobutyl]-1,2,3,6-tetrahydropyridine (HPTP), an intermediate metabolite of
      haloperidol.
AB  - The neuroleptic agent haloperidol (HP) is biotransformed to metabolites such as 4
      (4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-1,2,3,6- tetrahydropyridine
      (HPTP) and 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]pyridinium (HPP+).
      In this study, radioligand binding studies were performed using [3H]SCH23390 as a
      dopamine D1 receptor ligand and [3H]spiperone as a D2 ligand. Ki values for D1
      receptors were 35.8 microM and 54.9 microM for HP and HPTP, respectively.
      Corresponding values for D2 receptors were 39.1 nM and 329.8 nM. These results
      indicate similar low affinities in the micromolar range for both HP and HPTP at
      the dopamine D1 receptor, a much higher affinity of both HP and HPTP for the D2
      receptor than for the D1 receptor, and that HPTP binds to D2 receptors with a 9
      fold lower affinity than HP. The data are consistent with observations in mice
      that HPTP is a much less potent acute neuroleptic agent than HP.

PMID- 8761316
TI  - Study of the action of intramuscularly administered erythromycin on the L
      threonine transport and the digestive enzymatic activity in rabbit jejunum.
AB  - Erythromycin has been shown to inhibit the intestinal transport of L-threonine
      and D-galactose in strips of mucosal jejunum when it was directly added to the
      incubation medium. Nevertheless, the effect of erythromycin administered
      therapeutically by intramuscular injection on both the intestinal absorption of
      nutrients and the intestinal digestive activity, remains unknown. The results
      obtained show that, firstly, the intestinal absorption of L-threonine is
      inhibited in animals treated with erythromycin. The kinetic study shows that the
      effect seems to be mainly due to an alteration of the affinity apparent constant
      (Kt) of the Na(+)-dependent system of transport located in the mucosal border.
      However, the Na(+)-dependent L-threonine transport in BBMV was not altered by the
      treatment with erythromycin. The (Na(+)-K+) ATPase activity in BLMV from treated
      jejunum was 40% of the activity in control BLMV. Secondly, the treatment with
      erythromycin did not modify the digestive enzymatic activity of sucrase and
      aminopeptidase N.

PMID- 8761317
TI  - Differential effects of chronic calcium channel blocker treatment on the
      inotropic response of diabetic rat myocardium to acute ethanol exposure.
AB  - Cardiomyopathy is a consistent feature of diabetic myocardium as well as in
      prolonged alcohol consumption. Diabetes-induced myocardial dysfunction has been
      attributed, in part, to calcium overload within individual myocytes. The present
      study compares the effectiveness of the calcium channel blocker nifedipine
      (dihydropyridine-type) with verapamil (phenylalkylamine-type) in reversing
      myocardial dysfunction and diminishing the negative inotropic effect of ethanol
      on diabetic rat myocardium. Wistar rats were made diabetic with streptozotocin
      (55 mg/kg, i.v.) and isolated electrically stimulated papillary muscles were
      studied under isometric conditions in the absence and presence of clinically
      relevant concentrations of ethanol (80-240 mg/dl, i e., 17.4-52.1 mM). Subgroups
      of diabetic and normal animals received daily injections of verapamil or
      nifedipine 2 weeks after induction of diabetes for 8 weeks. Untreated diabetic
      animals exhibited hyperglycemia, hyperlipidemia, reduced growth, cardiomegaly,
      and hepatomegaly. Compared to verapamil chronic nifedipine treatment normalized
      or reversed the effects of diabetes on myocardial mechanical function. The
      negative inotropic effect of ethanol was attenuated only in muscles from
      verapamil-treated diabetic animals. Thus, chronic nifedipine treatment may be
      more effective than verapamil in reducing hyperglycemia, attenuating both cardiac
      and liver enlargement, and restoring myocardial mechanical function, in
      experimental diabetes. However, chronic verapamil therapy is more effective in
      diminishing the negative inotropic effect of ethanol on diabetic myocardium.
      These findings may have clinical significance among diabetic patients who consume
      alcoholic beverages while receiving long-term calcium blocker therapy.

PMID- 8761318
TI  - PAF-acetylhydrolase activity and PAF levels in pancreas and plasma of well-fed,
      diabetic and fasted rat.
AB  - PAF-AH activity was determined in pancreas homogenates. The enzyme activity was
      moderately stable upon storage at -20 degrees C. PAF and lyso-PAF were identified
      in rat pancreas and their concentrations were determined. PAF levels and PAF-AH
      activity were compared in the pancreatic tissue and plasma of three different
      groups of animals: well-fed, STZ-induced diabetic and fasted rats. The
      concentration of PAF in the pancreas of fasted rats was ten fold lower as
      compared with that of the well-fed or the diabetic animals. The last two groups
      had similar pancreatic PAF concentration. PAF levels in the plasma of fasted rats
      were seven fold lower than those of well-fed or diabetic rats, which were found
      to be similar. The enzyme PAF-AH had the highest activity in the pancreas of well
      fed rats. On the contrary, the enzyme seems to be more active in the plasma of
      fasted as compared with diabetic and well-fed animals.

PMID- 8761319
TI  - Effect of intratesticular administration of somatostatin on testicular function
      in immature and adult rats.
AB  - Somatostatin has been demonstrated in the testis. In the present investigations
      the effect of intratesticular injection of somatostatin on serum testosterone
      level and in vitro basal testosterone secretion of the testis was studied in
      immature and adult rats. Intratesticular injection of somatostatin in adult rats
      with two testes in situ decreased serum testosterone concentration and basal
      testosterone secretion in vitro. Similar treatment in immature animals had no
      effect on the parameters studied. In immature hemicastrates, however, local
      administration of the peptide induced a significant rise both in basal
      testosterone secretion in vitro and serum testosterone level, and resulted in an
      increase in testicular weight. In adult hemicastrates the peptide did not
      influence testicular functions. These results indicate that somatostatin might
      play a modulatory role in testicular steroidogenesis. The data also suggest that
      the effect of somatostatin is age-dependent, and that hemicastration might modify
      local action of the peptide.

PMID- 8761320
TI  - Enhanced vesiculation exacerbates complement-dependent hemolysis in glucose-6
      phosphate dehydrogenase deficient red blood cells.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficient red blood cells (RBCs) are
      known to be more susceptible to oxidant-induced hemolysis. Erythrocytes from G6PD
      deficient individuals are significantly more susceptible to Ca(2+)-induced
      vesiculation than normal control cells. The enhanced susceptibility of G6PD
      deficient RBCs to Ca(2+)-induced vesiculation is not due to ATP depletion. The
      remnant G6PD-deficient RBCs following vesiculation are more sensitive to
      complement-mediated hemolysis than control normal RBCs. A strong positive
      correlation exists between the level of Ca(2+)-induced vesiculation and the
      extent of complement mediated hemolysis.

PMID- 8761321
TI  - Inotropic agents differentially inhibit the induction of nitric oxide synthase by
      endotoxin in cultured macrophages.
AB  - We investigated the effects of inotropic agents with phosphodiesterase III
      inhibitory properties, amrinone, pimobendan and vesnarinone, and cell permeable
      cyclic nucleotide analogue, 8-bromo adenosine 3'5'-cyclic monophosphate (8 Br
      cAMP) on the induction of nitric oxide synthase (NOS) by lipopolysaccharide in
      J774A.1 macrophages in vitro. Although all three inotropic agents inhibited
      nitrite accumulation, the degree of inhibition was different, with pimobendan
      being the most potent inhibitor and amrinone the least. Vesnarinone inhibited
      nitrite formation biphasically. 8 Br-cAMP increased nitrite production at high
      concentrations, suggesting that the inhibitory effects of inotropic agents could
      not be explained by an increase in cAMP. Although differential inhibition of
      inducible NOS by inotropic agents may explain the different effects of these
      drugs in patients with heart failure, further study is necessary to reach this
      conclusion.

PMID- 8761322
TI  - Anticonvulsant activity of topiramate and phenytoin in a rat model of ischemia
      induced epilepsy.
AB  - Topiramate, a structurally novel anticonvulsant, and phenytoin were evaluated in
      a rat model of ischemia-induced epilepsy. In this model a transient global
      cerebral ischemia is induced by cardiac compression. By precisely controlling the
      experimental conditions the procedure causes reproducible neurological deficits
      that include audiogenic epileptic seizures. The seizures can be broadly separated
      into three types reflecting the degree of severity: wild running, clonic
      seizures, and tonic extension seizures of the forelimbs and hindlimbs. Topiramate
      and phenytoin blocked all three types of seizures. Calculated ED50 values for
      topiramate 1 hr after oral administration were 8.2, 13.0 and 36.1 mg/kg for
      blockade of tonic extension seizures, clonic seizures and wild running,
      respectively. Corresponding ED50 values for phenytoin were 5.0, 10.8 and 20.7
      mg/kg. These results support the concept that the anticonvulsant activity of
      these drugs is due primarily to an ability to block the spread of seizures.

PMID- 8761323
TI  - Calcium-related damage in ischemia.
AB  - The objective of this hypothesis article is to review evidence supporting a role
      for calcium in mediating ischemic brain damage, and to present data which puts
      mitochondrial dysfunction in the center of interest. The assumptions/postulates
      put forward, relating to global/forebrain and to focal ischemia, are as follows.
      (1) In brief ischemia of the global/forebrain type neuronal necrosis,
      particularly in the CA1 sector of the hippocampus, is conspicuously delayed. It
      is postulated that the initial events during ischemia, and in the immediate
      recirculation period, lead to a perturbation of cell calcium homeostasis, with a
      gradual postischemic rise in the free cytosolic calcium concentration (Ca2+i).
      When the latter reaches a certain limiting value mitochondria start accumulating
      calcium. It is hypothesized that intramitochondrial calcium accumulation triggers
      a permeability transition of the inner mitochondrial membrane (MPT), leading to
      production of reactive oxygen species, release of calcium, and an increase in the
      cytosol calcium concentration of a potentially adverse nature. (2) If ischemia of
      this "cardiac arrest" type is prolonged, or complicated by preischemic
      hyperglycemia, neuronal necrosis is enhanced and pan-necrotic lesions appear.
      Such insults are known to cause rapidly developing mitochondrial failure, but the
      involvement of calcium has not yet been demonstrated. (3) In focal ischemia, core
      tissues probably suffer a metabolic insult similar to that affecting brain
      tissues in global/forebrain ischemia. Thus, calcium influx and calcium overload
      of mitochondria are predictable, but available data only demonstrate rapidly
      developing, secondary energy failure, mitochondrial dysfunction, and enhanced
      influx of 45Ca. Thus, although secondary mitochondrial failure has been proved, a
      causative link between calcium influx and bioenergetic failure remains to be
      proved. Perifocal, penumbral tissues are exposed to spontaneously occurring
      depolarisation waves, leading to cellular efflux of K+ and influx of Ca2+. The
      latter may lead to gradual mitochondrial calcium overload triggering a MPT, and
      cell death. Although conclusive evidence has not yet been presented available
      results suggest a link between calcium influx, mitochondrial overload, and cell
      death.

PMID- 8761324
TI  - Apoptosis--the cell's silent exit.
AB  - Apo-ptosis, derived from Greek for 'falling off', can refer to the falling off of
      leaves during autumn (1), but is currently often used to describe a particular
      cell behaviour which occurs during development, cell maturation, in response to
      varying noxious stimuli or in disease. The cells die without causing their
      neighbours trouble, unlike necrotic cell death which is accompanied by an
      inflammatory response. In contrast, it is believed that during apoptosis cells
      neatly package their contents such as DNA, lipids and other biomolecules, and
      offer them to neighbouring cells which can take up these biomolecules by
      phagocytosis and use them in a type of environmental-friendly cellular recycling.
      It is these budding bodies that inspired the name apoptosis.

PMID- 8761325
TI  - The calcium hypothesis of brain aging and neurodegenerative disorders:
      significance in diabetic neuropathy.
AB  - In this paper we discuss the possible role of disturbed neuronal calcium
      homeostasis in brain aging and diabetic neuropathy. Disturbances in the
      homeostasis of cytosolic calcium concentration have been implicated in the
      pathogenesis of various acute and chronic neurodegenerative disorders and in
      brain aging. Obviously, these disorders do not all share the same pathogenetic
      mechanisms. However, a number of the pathogenetic mechanisms involved have in
      common that they may ultimately cause loss of calcium homeostasis, leading to
      neuronal damage. By identifying the possible role of calcium, treatment
      strategies can be developed that may be effective in a variety of
      neurodegenerative disorders, despite differences in their pathogenesis. Our aim
      is to explore some of the similarities that exist between a number of processes
      that have been implicated in the pathogenesis of brain aging and diabetic
      neuropathy, including ischemia, oxidative stress and non-enzymatic protein
      glycosylation. Each of these factors might impair neuronal calcium homeostasis,
      and ultimately lead to neurodegenerative changes. By discussing the putative role
      of these specific factors in two apparently dissimilar disorders, such as brain
      aging and diabetic neuropathy, we obviously do not intend to suggest that their
      pathogenesis is one and the same. Instead, by examining the relative role of
      these factors in two different types of neurodegenerative disorders we would like
      to emphasize the importance of disturbances in cellular calcium homeostasis as a
      final common pathway in neuronal damage resulting from various noxious events.

PMID- 8761326
TI  - Cytosolic Ca2+ buffering, a cell property that in some neurons markedly decreases
      during aging, has a protective effect against NMDA/nitric oxide-induced
      excitotoxicity.
AB  - In order to clarify the role of cytosolic Ca2+ buffering, a property that in
      living cells is sustained primarily by high affinity binding proteins, in NMDA
      receptor-sustained neuron excitotoxicity, cultures of the neuroblastoma line CHP
      100 (which is known to express the receptor) were loaded with the chelator BAPTA
      by incubation with various concentrations (0.03-1 microM) of its
      acetoxymethylester derivative. The effectiveness of the loading in terms of
      cytosolic buffering was confirmed by fura-2 measurement experiments in which the
      [Ca2+]i transients induced by cell exposure to ATP were blunted in the initial
      peak (up to -75%) and also in the following plateau. When the BAPTA-loaded
      neuroblastoma cells were exposed to NMDA (1 mM), excitotoxicity was reduced dose
      dependently up to almost 70%, while the generation of cGMP was inhibited up to
      completion. The latter result suggested the possible involvement of nitric oxide
      in the NMDA-induced excitoxicity, a mechanism confirmed by the dose-dependent
      inhibitory effect induced by the nitric oxide synthase blocker, L-N-(1
      iminoethyl)-ornithine, which protected the cells completely when administered at
      300 microM. Flow cytometry analysis of DNA revealed that the mechanism of
      excitotoxicity in CHP100 cells does not involve apoptosis. We conclude that
      cytosolic Ca2+ buffering, a property known to vary considerably among neuronal
      cells and to change in some neurons also during ageing, has a general protective
      effect. Such a protection appears to take place via the blunting of the glutamate
      induced [Ca2+]i responses mediated by the NMDA receptor, with prevention of the
      ensuing overactivation of nitric oxide synthase and of the irreversible
      derangement of the ionic homeostasis of the cell.

PMID- 8761327
TI  - Aging-related increase in hippocampal calcium channels.
AB  - This paper briefly reviews more than 10 years of our studies on brain aging and
      voltage-activated calcium (Ca) currents in rat hippocampal CA1 neurons. Initial
      studies in the hippocampal slice preparations found that synaptic plasticity was
      impaired with aging, apparently due to excess Ca influx. In subsequent analyses
      it was found that the Ca-dependent afterhyperpolarization, the Ca action
      potential and voltage-activated Ca currents were all increased in aged CA1
      neurons. This was not due to impaired inactivation processes. Multiple types of
      Ca channels appear to be affected by aging. A long Ca tail current was also found
      in these studies, which seems to represent an unrecognized and significant Ca
      entry pathway at resting potential. In primary cell cultures, Ca currents and
      single Ca channels increase steadily over the life cycle of the cultured neurons
      and are correlated with cell death. Single L-type Ca channels were also studied
      in brain neurons of an aged mammal (rat), using the partially dissociated
      ("zipper") hippocampal slice preparation. A substantial increase in the density
      of functionally available Ca channels was present in CA1 neurons of aged rats,
      similar to the increase seen in cultured neurons. Thus, a gradual increase in the
      density of Ca channels appears to be a consistent property of hippocampal
      neuronal aging and might well be a factor in the vulnerability of aged neurons to
      Alzheimer's disease and other neurodegenerative/traumatic conditions.

PMID- 8761328
TI  - Decreased plasma membrane calcium transport activity in aging brain.
AB  - We have assessed the functional properties of both calmodulin (CaM) and the
      plasma membrane Ca(2+)-ATPase in brains of young, middle aged, and old Fisher 344
      rats. Under optimal conditions of saturating Ca2+ and ATP, the CaM-activated
      Ca(2+)-ATPase activity was decreased with increasing age, particularly when CaM
      isolated from the brains of aged rats was used to stimulate the enzyme. In the
      case of CaM, structural modifications within the primary sequence of the protein
      from aged brains were identified. We found that during normal biological aging
      approximately 6 methionine residues were modified to their corresonding sulfoxide
      per CaM, and no other amino acids were modified. Some aspects of the age-related
      decline in the effectiveness of CaM as an activator of Ca(2+)-ATPase could be
      simulated using a range of reactive oxygen species (including hydrogen peroxide
      and oxoperoxynitrite) and, in the latter case, the extent of oxidative
      modification of specific methionine residues was directly related to their
      surface accessibility. The pattern of oxidative modification of the methionines
      in the aged CaM was less straightforward, though both in vitro oxidation of CaM
      and aging within the brain markedly decreased the functional properties of this
      important Ca(2+)-regulating protein.

PMID- 8761329
TI  - Calcium-dependent afterhyperpolarization and learning in young and aging
      hippocampus.
AB  - Hippocampally-dependent trace eyeblink conditioning has been shown to be affected
      by aging. Aging animals take more trials to acquire the association and are more
      likely to be unable to learn the task. Hippocampal neurons show decreased post
      burst afterhyperpolarizations (AHPs) and less accomodation after conditioning, in
      a time-dependent fashion which may relate to the role of hippocampus in learning
      consolidation. CA1 neurons in aging rabbits show increased AHPs and more
      accomodation, i.e., they are less excitable, and larger calcium action
      potentials. These age-related changes may underlie the learning deficits in aging
      rabbits. The lipophylic calcium channel blocker nimodipine reduces the AHP,
      accomodation and calcium action potential at low concentrations in aging but not
      young CA1 neurons. Nimodipine also enhances learning rate in a variety of tasks,
      including eyeblink conditioning, in aging but not young animals and humans.
      Altered calcium handling by neurons of aging mammals is a striking change, is
      pharmacologically manipulable, and may be an important factor in altered learning
      and cognitive abilities in the aging.

PMID- 8761330
TI  - Synaptic mechanisms and calcium binding proteins in the aged rat brain.
AB  - Synaptic mechanisms were studied ex vivo in the aged rat hippocampus, using a
      slice preparation and intracellular electrophysiological recordings of the CA1
      pyramidal neurons. A dramatic depression of the slow cholinergic excitatory
      postsynaptic potential (EPSP) and of the slow, GABAB-mediated inhibitory
      postsynaptic potential (IPSP) were observed. These age-related changes were
      consistently found in three different strains of rats. The mechanisms involve 1)
      changes in the properties of the postsynaptic muscarinic receptors, and possibly
      in acetylcholine release (for the postsynaptic muscarinic receptors, and possbily
      in acetylcholine release (for the cholinergic EPSP), and 2) alterations in the
      presynaptic GABAergic interneurons, as shown by a loss in calbindin
      immunoreactivity (for the GABAergic IPSP). The immunoreactivity for three calcium
      binding proteins (calbindin, parvalbumin and calretinin) was studied in the aged
      rat brain. Immunoreactivity for calbindin was dramatically reduced in the
      pyramidal neurons of the CA1 field and in a subpopulation of interneurons in the
      hippocampus. Immunoreactivity for parvalbumin was reduced in the medial septal
      area, and in the cingulate cortex, whereas no change was observed for calretinin.
      These age-related alterations could 1) modify the functions of the hippocampal
      networks, and possibly contribute to the age-related cognitive deficits, and 2)
      compromise intraneuronal calcium buffering, and thus make neurons more vulnerable
      to toxic insults.

PMID- 8761331
TI  - Cytosolic and mitochondrial calcium in synaptosomes during aging.
AB  - Synaptosomal [Ca2+]i levels increase during aging, particularly in the old rat
      hippocampus, both under basal conditions and after high K depolarization. This is
      probably the result of age-dependent modifications in calcium buffering and
      extrusion systems rather than due to increased calcium influx, since calcium
      uptake through synaptosomal voltage gated calcium channels decreases in old
      animals. The calcium binding capacity of the cytosolic compartment (i.e, that
      excluded from mitochondria and endoplasmic reticulum) of synaptosomes was
      markedly reduced in old rats. Calcium compartmentation in synaptosomal
      mitochondria, is also reduced during aging, and this is associated with a
      decrease in activity of the mitochondrial calcium uniporter. Taken together,
      these modifications point towards a clear deterioration of the cell calcium
      homeostatic mechanisms towards increased [Ca2+]i in old age, specially under
      conditions of high calcium loads, a situation that may exacerbate neuronal
      vulnerability to excitotoxicity.

PMID- 8761332
TI  - Down-regulation of free intracellular calcium in dissociated brain cells of aged
      mice and rats.
AB  - Age-related changes in resting levels of the free intracellular calcium
      concentration ([Ca2+]i) as well as alterations of the rise in [Ca2+]i following
      depolarization have been investigated in acutely isolated cells of the mouse
      brain and of various regions of the rat brain. Resting [Ca2+]i as well as Ca2+
      responses after depolarization were lower in brain cells of aged mice and in
      hippocampus and cortex cells, but not striatum or cerebellum cells of aged rats.
      It is concluded that the Ca2+ homeostasis is specially susceptible to the aging
      process in some brain regions only, resulting in a down regulation of [Ca2+]i
      probably as a consequence of an enhanced sensitivity of mechanisms regulating
      [Ca2+]i. This speculation was confirmed by an enhanced sensitivity of Ca(2+)
      stimulated phospholipase C activity in the aging mouse brain. The alterations of
      the central Ca2+ homeostasis in the mouse and the rat were paralleled by
      comparable changes of [Ca2+]i in spleenocytes of both species in aging. The rise
      of [Ca2+]i after stimulation with the mitogen phytohemagglutinin (PHA) was
      significantly reduced in the plateau phase, which is maintained by Ca2+ influx
      mechanisms. Moreover, a reduced Ca2+ response was also found after stimulation of
      the cells with the Ca2+ ionophore A23187. The data may indicate that comparable
      disturbances of the Ca2+ homeostasis occur in central and peripheral cells and
      that these alterations mainly affect transmembraneous Ca2+ fluxes rather than
      Ca2+ release from intracellular stores. These alterations may be compensated
      under normal conditions. However, in situations of additional stress like
      ischemia or hypoglycemia, the preexisting alterations of Ca2+ homeostasis may
      result in a reduced capacity for adaptation. This assumption was supported by
      observations indicating that the down-regulation of [Ca2+]i after subchronic
      treatment with nimodipine (20 mg/kg, 14 days) was less in brain cells of aged
      than of young mice.

PMID- 8761333
TI  - Calcium homeostasis in aged neurones.
AB  - Mechanisms of cytoplasmic calcium homeostasis were investigated in peripheral and
      central neurones isolated from neonatal, adult and old Wistar rats and in granule
      neurones in acutely prepared cerebellar slices of adult and old CBA mice. The
      cytoplasmic calcium concentration ([Ca2+]i) was measured by either indo-1-or fura
      2-based microfluorimetry. The resting [Ca2+]i was significantly higher in senile
      neurones. The depolarization-induced [Ca2+]i transients were markedly altered in
      old neurones when compared with adult ones: the age-associated changes in
      stimulus-evoked [Ca2+]i signalling comprised of (i) significant decrease of the
      amplitudes of [Ca2+]i transients; (ii) prolongation of the rising phase and (iii)
      prominent deceleration of the recovery of the [Ca2+]i elevation towards the
      resting level after the end of depolarization. The amplitudes of calcium release
      from caffeine/Ca(2+)-sensitive endoplasmic reticulum calcium stores became
      significantly smaller in old central neurones, whereas they remained unaffected
      in peripheral neurones. Based on our observations we can conclude that ageing of
      the nervous system is associated with significant changes in mechanisms of
      [Ca2+]i homeostasis in individual neurones. These changes lead to a stable
      increase in the resting [Ca2+]i and to a substantial prolongation of stimulus
      evoked [Ca2+]i signals. We could suggest also that the ability of the old
      neurones to handle Ca2+ loads is diminished, which may determine higher
      vulnerability of aged neurones to excess of calcium ions.

PMID- 8761334
TI  - Peripheral cells as an investigational tool for Alzheimer's disease.
AB  - A number of abnormalities in metabolic and biochemical processes have been found
      in cultured skin fibroblasts derived from patients affected by Alzheimer's
      disease (AD). An example of the successful use of peripheral cells to examine a
      cell biological abnormality in AD are the studies on transduction systems and on
      APP metabolism, mostly performed on fibroblasts from AD donors. In fact, some of
      the described alterations mirror events that have also been demonstrated to occur
      in the AD brain. Within this context data obtained using peripheral cells may
      help to identify and to test hypotheses on the primary pathophysiological
      mechanisms leading to AD. In perspective, the identification of peripheral
      biological markers could provide a useful aid in AD and could allow
      identification of stages of of the disease or subgrouping of patients, possibly
      helping to predict the response to treatment.

PMID- 8761335
TI  - Calcium signals in T lymphocytes from old mice.
AB  - Mitogen-induced increases in free calcium ion concentration ([Ca]i) are a key
      element of the process by which T lymphocytes are induced to proliferate and
      differentiate into effector cells. T cells from old mice exhibit lower average
      rises in calcium concentration than T cells from young donors when stimulated
      with either mitogenic lectins or antibodies to the CD3 chains of the antigen
      receptor. The decline with age in calcium signal generation is largely
      attributable to a shift from naive to memory T cells, in that memory T cells,
      from mice of any age, are more resistant to mitogen-induced changes in [Ca]i. The
      decline in calcium signal generation is likely to be functionally significant,
      since T cells isolated on the basis of poor calcium signals show diminished
      ability to produce and to respond to the growth factor IL-2. Con A induces a
      transient increase in uptake of radiolabeled calcium from extracellular sources,
      and the extent of this increase declines with age. Alterations in production of
      inositol tris-phosphate (IP3) seem not to contribute to age-related changes in
      calcium signal generation. T cells from old mice, and memory T cells from mice of
      any age, are relatively resistant to increases in [Ca]i even when these are
      induced by receptor-independent stimuli such as the calcium ionophore ionomycin.
      The ionomycin-resistance of memory T cells suggests that these cells may have an
      augmented ability to buffer changes in [Ca]i, perhaps by increased activity of
      the ATP-dependent plasma membrane calcium pump. It seems likely that age-related
      declines in calcium signal generation contribute to the functional
      immunodeficiency of old age.

PMID- 8761336
TI  - Altered oxidation and signal transduction systems in fibroblasts from Alzheimer
      patients.
AB  - Abnormalities in calcium regulation, amyloid-beta-protein (A beta) production and
      oxidative metabolism have been implicated in Alzheimer's disease (AD). The use of
      cultured fibroblasts complement post-mortem and genetic approaches in clarifying
      the interaction of these processes and the underlying mechanism for the changes
      in AD. Definition of gene defects in particular Alzheimer families (FAD) permits
      elucidation of the role of those genetic abnormalities in altered signal
      transduction in cell lines from those families. Abnormalities in calcium
      regulation, ion channels, cyclic AMP, the phosphatidylinositide cascade and
      oxidative metabolism are well documented in fibroblasts from patients with
      primary genetic defects in the presenilins. Recent studies in AD fibroblasts that
      demonstrate abnormal secretion of A beta, a protein known to form the
      characteristic extracellular amyloid deposits in AD brain, further supports the
      use of these cells in AD research. Comparison of changes in calcium signaling,
      mitochondrial oxidation and A beta production in these cells suggests that
      changes in signal transduction including calcium may be a more consistent
      observation than altered A beta production in fibroblasts from some FAD families.
      An understanding of these abnormalities in fibroblasts may provide further
      insights into the pathophysiology of AD, new diagnostic measures and perhaps
      innovative therapeutic approaches.

PMID- 8761337
TI  - Soluble beta-amyloid induces Alzheimer's disease features in human fibroblasts
      and in neuronal tissues.
AB  - It has been shown that K+ channels, Cp20 (a 20kD GTP-binding protein), and
      intracellular calcium release, play a key role in associative memory storage.
      These same elements have been shown to be altered in fibroblasts from Alzheimer's
      Disease (AD) patients. In addition, it has been shown that PKC, also implicated
      in memory storage and closely related to the above mentioned components, is also
      altered in AD fibroblasts. Moreover, beta-amyloid was capable of inducing an AD
      like phenotype for K+ channels and Cp20 in otherwise normal fibroblasts,
      providing additional evidence for the potential involvement of these components
      in AD and suggesting a possible pathological consequence of soluble beta-amyloid
      elevation in AD. Preliminary evidence shows that comparable changes in potassium
      channel function are also present in human olfactory neuroblasts from AD
      patients. These results indicate that the observed changes not only occur in
      peripheral tissues such as fibroblasts, but also in neural tissue, the primary
      site of AD pathology.

PMID- 8761338
TI  - Lymphocytes and neutrophils as peripheral models to study the effect of beta
      amyloid on cellular calcium signalling in Alzheimer's disease.
AB  - According to the calcium hypothesis of brain aging, disturbances of free
      intracellular calcium homeostasis ([Ca2+]i) play a key role in pathology of
      Alzheimer's disease (AD). Recent data from neuronal tissue culture support the
      contribution of the beta-amyloid peptide (beta A) to neurodegeneration in AD,
      probably by disruption of the intracellular Ca2+ regulation. On the basis of this
      premise, we used peripheral blood cells to examine the role of beta A on Ca2+
      signalling, not only to obtain an experimental approach to investigate these
      effects of beta A in man, but also to search for AD-specific alterations of the
      effects of beta A on Ca2+ signalling. This approach is based on observations
      indicating that the phytohemagglutinin (PHA)-induced Ca2+ response in circulating
      human lymphocytes of healthy volunteers is affected by beta A and its fragment 25
      35 in a fashion similar to its effects on central neurons, whereas we found no
      effect of beta A on receptor-activated Ca2+ response in neutrophils. Therefore,
      we used human blood lymphocytes as peripheral model systems to search directly
      for AD-related abnormalities of Ca2+ regulation, for alterations of beta A
      effects on Ca2+ signalling and on membrane fluidity, and for possible changes of
      potassium channels. In accordance with our data in neutrophils, we were unable to
      identify any relevant change of the PHA-induced Ca2+ elevations in lymphocytes,
      which is not supporting the assumption of general alterations of cellular Ca2+
      regulation in AD. On the other hand, the amplifying effect of beta A on Ca2+
      signalling was significantly reduced in lymphocytes from AD patients. Moreover,
      Ca2+ responses to beta A25-35 were not different between early- and late-onset AD
      patients. Our findings indicate that the sensitivity of the lymphocyte for the
      effects of beta A is reduced in a high percentage of patients with probable or
      possible AD. As possible explanation we observed a similar reduction of the
      sensitivity of the lymphocyte membrane for the fluidity-decreasing properties of
      beta A. Finally, the inhibition of the PHA-induced Ca2+ response by
      tetraethylammonium (TEA) was lower in the AD group compared to aged controls.
      This could suggest the presence of a K+ channel dysfunction on AD lymphocytes, as
      it has been shown on skin fibroblasts of AD patients.

PMID- 8761339
TI  - Stability study on renal type I mineralocorticoid receptor.
AB  - The purpose of this work is to review stability and activation properties of type
      I receptor, in order to explain the reasons for its extreme in vitro instability.
      We demonstrate that the treatment of rat kidney cytosol with H2O2 prevents
      aldosterone binding, DNA/steroid-receptor complex interactions, and prevents the
      receptor thermal inactivation. In contrast, exogenous sulfhydryl reducing
      reagents are necessary to insure maximum binding of mineralocorticoid receptor
      and DNA/steroid-receptor interaction. However, the presence of beta
      mercaptoethanol in thermal induced incubations reverts the H2O2 protection. We
      also demonstrate that contaminations with free or sequestered iron are harmful
      for both, receptor binding capacity (in a reversible form) and for hormone
      receptor/DNA binding properties (in a partially reversible form). We propose a
      sulfhydryl oxidative mechanism for type I mineralocorticoid receptor inactivation
      in which iron contaminants might accelerate this process by oxidative catalysis.
      We also demonstrate that when thiol groups are blocked by specific reagents such
      as N-ethyl-maleimide or dithionitrobenzoic acid, type I sites loose binding
      capacity, but the protein is protected from oxidation as well as inactivation.

PMID- 8761340
TI  - Endothelin-1 induces an increase in total protein synthesis and expression of the
      smooth muscle alpha-actin gene in vascular smooth muscle cells.
AB  - The growth response of aortic vascular smooth muscle cells (VSMCs) to chronic
      hypertension includes vascular hypertrophy. We have shown previously that
      angiotensin II positively regulates the expression of the human vascular smooth
      muscle (SM) alpha-actin gene. To further expand our understanding of vasoactive
      peptide-induced vascular hypertrophy, we studied endothelin-1 (ET-1) regulation
      of total protein synthesis and cytoskeletal gene expression in VSMCs. In a
      concentration-dependent manner ET-1 increased [3H] leucine incorporation by VSMCs
      (122.4 +/- 5.5%, mean +/- SEM, n = 5). ET-1 (0.1 microM) induced expression of SM
      alpha-actin mRNA as detected by Northern blot analysis. Also, ET-1 in a
      concentration-dependent manner (0.1 nM-0.1 microM) induced expression of the
      chloramphenicol acetyl transferase gene driven by 896 bp of the human SM alpha
      actin promoter when transiently transfected into rat aortic VSMCs by the calcium
      phosphate method (141.2 +/- 9.8%, mean +/- SEM, n = 10). These data suggest that
      part of ET-1-induced increase in protein synthesis is achieved through
      transcriptional regulation of the SM alpha-actin gene via activation of cis
      acting element(s) in the promoter. Such findings help elucidate the role of ET-1
      in regulation of vascular growth.

PMID- 8761341
TI  - The in vitro action of polyamines on rat basilar and femoral artery contractile
      activity.
AB  - This study was performed to assess the role of exogenously administered
      polyamines on rat basilar and femoral artery contractile activity in vitro. With
      the endothelium removed, rings of tissue were set up in organ chambers to measure
      isometric tension. The polyamines (0.1-3 mM), putrescine, spermidine, and
      spermine, were added to the tissue baths; after 30 min of incubation a cumulative
      concentration response curve (CRC) was obtained with either KCl or serotonin (5
      HT). Additional CRCs were run with Ca(2+) in high K+ Krebs (60 mM). In both
      tissues, the CRCs to KCl were shifted to the right in a dose-dependent manner for
      spermidine and spermine (1 & 3 mM) but not putrescine. Spermine (3 mM) depressed
      the KCl maxima by 18.6% and 10.1% in the basilar and femoral artery respectively.
      For 5-HT CRCs, only spermine (3 mM) slightly inhibited the maximal response in
      both tissues. The most potent action of spermine was on inhibition of Ca(2+)
      responses in high K+ where the EC50S were shifted 3.5 and 10 fold over control
      values in the basilar and femoral respectively. We conclude spermidine and
      spermine, but not putrescine, attenuate vascular smooth muscle contractions on
      the basilar and femoral arteries in vitro. The exact nature of the inhibition
      remains to be fully explored, but blockade of calcium entry through voltage
      operated Ca channels may play a role. Thus, certain polyamines may affect
      cerebral perfusion by inhibition of vascular contractility.

PMID- 8761342
TI  - Evidence against the involvement of reactive oxygen species in the pathogenesis
      of neuronal death in Down's syndrome and Alzheimer's disease.
AB  - It has been proposed that the pathogenesis of Down's Syndrome (DS) involves
      reactive oxygen species (ROS) arising from a gene dosage effect that
      disproportionately elevates superoxide dismutase (SOD1) activity. It was also
      suggested that generation of ROS might be responsible for neuronal death in
      Alzheimer's Disease (AD). Little data on brain ROS in DS and AD exist; therefore,
      we determined activities of choline acetyltransferase (ChAT) and of the oxidative
      defense enzymes SOD1 and glutathione peroxidase (GSHPx) in frontal cortex of aged
      patients with DS and AD. We also measured levels of malondialdehyde, which
      reflects lipid peroxidation, and o-tyrosine, which represents the hydroxyl
      radical attack. ChAT was significantly reduced in cortex of patients with DS (
      68%) and AD (-66%) as compared to controls. There were no statistically
      significant differences, however, between controls and both neurodegenerative
      disorders for SOD1, GSHPx, malondialdehyde and o-tyrosine. Our data contradict
      the only previous finding on increased SOD1 and ROS in brains of patients with
      DS: age as well as methodological differences might account for the discrepancy.
      In conclusion, no evidence for a pathogenetic role of SOD1, GSHPx, lipid
      peroxidation or hydroxyl radical attack in aged patients with DS and AD could be
      provided.

PMID- 8761343
TI  - Amyloidogenic processing of Alzheimer's amyloid precursor protein in vitro and
      its modulation by metal ions and tacrine.
AB  - Recent studies implicate that excessive amyloidogenic pathway of amyloid
      precursor protein (APP) processing may be the final common pathway involved in
      the pathogensis of AD. In attempts to identify the proteases or factors leading
      to excessive amyloid deposition, we evaluated the potential role of
      acethylcholinesterase (AChE) and its associated protease for amyloidogenic
      processing of APP in vitro. Prolonged incubation of a recombinant APP770 with
      AChE produced several amyloidogenic fragments accumulating a relatively stable a
      18 kDa A beta (amyloid beta-protein) bearing carboxy terminal peptide, which was
      further degraded by an increased concentration of AChE. Protease inhibitory
      profiles confirmed the trypsin-like serine protease activity present in AChE
      preparation. This observed APP processing was significantly enhanced by Ca2+,
      Mg2+, or Mn2+ at 1 mM concentration and modulated in concentration dependent
      manners by metal ions such as Ca2+, Zn2+, Fe2+/Fe3+, Al3+, or a tacrine, a
      centrally active cholinesterase inhibitor. Our data imply that AChE and its
      associated protease may be involved in the generation a 18 kDa amyloidogenic
      peptide under certain physiological condition in vivo and that the gradual
      changes in their proteolytic activities or locations and the locally disturbed
      metal homeostasis could be factors associated with abnormal accumulation of APP,
      eventually leading to amyloid deposition in AD brain. In addition, zinc or
      tacrine treatment of AD patients with high dosage or in the long term may have
      effects on the process of amyloidogensis.

PMID- 8761344
TI  - Inhibition of platelet aggregation by endocardial endothelial cells.
AB  - We assessed the anti-platelet properties of endocardial endothelial cells (EECs)
      by measuring platelet aggregation after brief interaction with EECs isolated from
      the right ventricles of porcine hearts. Platelet aggregation in response to
      thrombin was significantly inhibited by brief incubation of platelet suspensions
      over EEC monolayers. Pretreatment of EECs with indomethacin restored platelet
      reaction but that with L-NAME and hemoglobin (Hb) did not. The PGI2 content of
      platelet suspensions after interaction with cultured EECs was significantly
      correlated with the inhibition of platelet aggregation. These results suggest
      that EECs inhibit platelet aggregation by releasing PGI2.

PMID- 8761345
TI  - Muscarinic agonist inhibition of rat striatal adenylate cyclase is enhanced by
      dopamine stimulation.
AB  - Rat striatal adenylate cyclase stimulated with combinations of 100 microM
      dopamine plus 40-100 nM forskolin was inhibited to a significantly greater extent
      by the muscarinic agonist carbachol than was forskolin-stimulated activity in the
      absence of dopamine. In the presence of Ro 201724 as phosphodiesterase inhibitor,
      a 100 microM concentration of the adenosine agonist 2-chloroadenosine stimulated
      adenylate cyclase activity 6.6 -fold over basal activity. In contrast to dopamine
      stimulated activity, carbachol did not significantly inhibit adenylate cyclase
      activity elevated by the adenosine agonist, indicating specificity of the
      muscarinic response for dopamine stimulation. The effects of muscarinic
      antagonists on striatal versus heart adenylate cyclase indicated that the
      striatal response was mediated primarily through M4 receptors. The present
      results suggest that muscarinic M4 and dopamine D1 receptors are co-localized and
      functionally coupled in rat striatum.

PMID- 8761346
TI  - Plasma protein-bound sulfhydryl group oxidation in humans following a full
      marathon race.
AB  - Physical exercise can induce oxidative stress in humans. We studied the influence
      of aerobic exercise on the status of plasma protein-bound sulfhydryl groups in
      seven moderately-trained male college students who participated in a full
      marathon race. The plasma protein-bound sulfhydryl group values were
      significantly declined immediately after the race (-22%, p < 0.01), and 24 h (
      12%, p < 0.01) and 48 h (-13%, p < 0.01) after the race, as compared to the
      baseline value. The plasma concentrations of thiobarbituric acid reactive
      substances were unchanged following the race, while the activities of plasma
      creatine kinase were significantly increased, indicating skeletal muscle damage.
      These results suggested that prolonged exercise may cause the oxidation of plasma
      proteins.

PMID- 8761347
TI  - Interspecies scaling: a comparative study for the prediction of clearance and
      volume using two or more than two species.
AB  - The prediction of pharmacokinetic parameters in humans from data obtained in
      lower animals can be of considerable importance in the process of drug
      development. Successful extrapolation will facilitate drug dosing transitions
      from animals to man and accelerate the drug testing process. Existing literature
      indicates that for the prediction of pharmacokinetic parameters, data from at
      least three animal species are used. Some investigators have used only two
      species to predict clearance and volume in humans. The objective of this paper is
      to investigate and try to determine if a two species scale-up model is as
      reliable as a three or more species model. Twelve compounds were chosen randomly
      from literature and clearance and volume of distribution were scaled-up from two
      species and compared to predictions obtained from more than two species. The
      findings in this study indicate that: (1) three or more species are needed for a
      reliable prediction of clearance; and (2) volume of distribution of a compound is
      predicted equally well using data from two species or more.

PMID- 8761349
TI  - Correlation between inhibition of growth and arginine transport of Leishmania
      donovani promastigotes in vitro by diamidines.
AB  - Diamidines are known to possess potent antiprotozoal activity due to their
      property of binding with DNA minor groove. Pentamidine or 1,5-bis-(4'
      amidinophenoxy)pentane, is the most known aromatic diamidine and is used to treat
      cases of antimony resistant leishmaniasis. Yet, it suffers from limited clinical
      application due to its adverse and toxic side effects. A set of four structural
      analogs of pentamidine along with the known antileishmanial diamidines viz.,
      pentamidine, berenil and dibromopropamidine, were tested for their effect on
      growth of Leishmania donovani promastigotes in vitro using 3H-thymidine
      incorporation as the growth parameter. In view of structural similarity between
      amidino moiety of diamidines and guanidino group of L-arginine and also the
      previous report from this laboratory regarding presence of a novel arginine
      transporter in Leishmania donovani promastigotes, a parallel study was also
      conducted with the analogs and standard diamidines for their inhibitory effect on
      leishmanial arginine transport function. Bisbenzyl pentamidine and biscyclopropyl
      pentamidine were identified as considerably more potent inhibitors of growth and
      arginine transport function of leishmania promastigotes in vitro than the parent
      drug, pentamidine. A linear correlation was established between inhibition of
      parasite growth and arginine transport with regard to standard diamidines as well
      as novel analogs. Inhibition of arginine transport by dibromopropamidine and
      Pentamidine was competitive. The diamidines possibly gain entry into leishmania
      cells through arginine transporter.

PMID- 8761348
TI  - Effects of glucose and oxygen deprivation on phosphoinositide hydrolysis in
      cerebral cortex slices from neonatal rats.
AB  - The effects of glucose deprivation, hypoxia and glucose-free hypoxia conditions
      on phosphoinositide (PI) hydrolysis were studied in cortical slices from 8-day
      old rats. Only glucose-free hypoxia induced a significant increase of inositol
      phosphate formation. The inositol phosphate formation induced by noradrenaline,
      carbachol and several excitatory amino acid receptor agonists, but not the Ca2+
      ionophore A23187-induced stimulation, was blocked by glucose-free hypoxia and
      differentially reduced by glucose and oxygen deprivation depending on the
      neurotransmitter receptor agonist. The stimulatory effect of glucose-free hypoxia
      was not reduced by the muscarinic receptor antagonist atropine or by the
      inhibitors of the excitatory amino acid-stimulated PI hydrolysis DL-2-amino-3
      phosphono-propionic acid and L-aspartate-beta-hydroxamate, and neither by the
      voltage-sensitive Na+ channel tetrodotoxin. The effect of glucose-free hypoxia
      was partially dependent on extracellular Ca2+ and it was blocked by verapamil and
      amiloride, but not by nifedipine, Co2+ and neomycin. These results suggest that
      Ca2+ influx through the Na(+)-Ca2+ exchanger underlies the PI hydrolysis
      stimulation induced by combined glucose and oxygen deprivation in neonatal
      cerebral cortical slices.

PMID- 8761350
TI  - The synovial-like membrane at the bone interface in loose total hip replacements
      contains high levels of extracellular group II phospholipase A2.
AB  - Progressive lysis of bone in loose total hip replacement has been ascribed to the
      capacity of the synovial-like membrane present at the bone interface to produce
      prostaglandin E2 and cytokines such as tumor necrosis factor (TNF alpha).
      Phospholipase A2 (PLA2) produces rate limiting precursor i.e. arachidonic acid in
      the biosynthesis of various types of biologically active lipids including
      prostaglandins. It has been shown that extracellular human group II phospholipase
      A2 is present in large amount in synovial fluid of patients with synovitis and
      that the expression of this enzyme is under the control of cytokines such as TNF
      alpha. Furthermore, the human extracellular enzyme has been also shown to induce
      in an experimental animal model to cause disruption of a synovial like membrane
      without increasing prostaglandin production. Here we have evaluated PLA2 and TNF
      alpha levels in the supernatant of homogenate of the synovial-like membrane
      present at the bone interface retrieved from six patients with a loose non septic
      failed total hip replacement. In all the membranes examined were found high
      levels of both TNF alpha (856 +/- 211 units/ml) and extracellular phospholipase
      A2 (2616 +/- 862 ng/ml). These findings suggest that extracellular PLA2 may play
      a major role in the process that cause disruption of the membrane at the bone
      prosthesis interface.

PMID- 8761351
TI  - Preclinical evaluation of single-cell oils that are highly enriched with
      arachidonic acid and docosahexaenoic acid.
AB  - Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important in human
      brain and retina development, and there is growing evidence showing the
      importance of these fatty acids in infant nutrition. Triglyceride oils, highly
      enriched in ARA (ARASCO) and DHA (DHASCO), were evaluated using very high dose
      acute (20 g/kg) and 4-wk subchronic gavage feedings in weanling Sprague-Dawley
      rats. The combination of these oils, Formulaid, was also tested in the 4-wk
      subchronic study, ARASCO, DHASCO and Formulaid were found to have a no-observable
      adverse-effect level of more than 2.5 g/ kg/day, 1.25 g/kg/day and 3.75 g/kg/day,
      respectively. This represents a 50-fold safety margin over the intended use of
      Formulaid in infant formula. Survival, clinical signs, body weight gain, food
      consumption, haematology, clinical chemistry and histopathological evaluations
      failed to show any significant differences in animals administered ARASCO, DHASCO
      or Formulaid compared with that in control animals administered equal amounts of
      high oleic sunflower oil. The bioavailability of ARASCO, DHASCO and Formulaid was
      verified by increases in DHA and ARA levels in heart and liver tissues in these
      animals. Because these oils are enriched in only a single bioactive fatty acid,
      and they have been shown to be safe, they may offer a new source of these fatty
      acids in speciality foods such as infant formula.

PMID- 8761352
TI  - Differential induction of isozymes of drug-metabolizing enzymes by butylated
      hydroxytoluene in mice and Chinese hamsters.
AB  - Induction of isozymes of drug-metabolizing enzymes by butylated hydroxytoluene
      (BHT) was studied in the male ddY mouse and Chinese hamster. In mice given 0.05
      and 0.15% BHT in the diet for 14 days cytochrome P-450 contents and the
      activities of uridine diphosphate-glucuronyl transferase (UDP-GT) and
      pentoxyresorufin O-dealkylase were markedly increased, while in those fed 0.15%
      BHT testosterone 6 alpha-, 16 alpha- and 16 beta-hydroxylases were greatly
      increased, which indicated induction of cytochrome P-450 isozymes of the CYP2B
      family. Western blot analysis also showed an increased level of the isozyme
      immunorelated to rat CYP2B2 by BHT feeding. The activities of aryl hydrocarbon
      hydroxylase, ethoxycoumarin O-deethylase (ECOD), erythromycin N-demethylase and
      glutathione S-transferase (GST) remained unchanged. In Chinese hamsters given
      0.05 and 0.15% BHT in the diet for 14 days activities of ECOD and GST were
      induced, but cytochrome P-450 contents and the activities of other enzymes were
      unaffected. Testosterone 15 alpha-hydroxylase was induced in hamsters fed 0.15%
      BHT. These findings suggested that BHT administration in the hamster induced
      CYP2A2-type isozyme, which was confirmed by Western blot analysis. BHT treatment
      enhanced activation of benzo[a] pyrene (B[a]P) as determined by the mutagenicity
      test, especially in Chinese hamsters. The results suggest that BHT treatment
      induces specific isozymes of drug-metabolizing enzymes and might modify the
      expression of toxicities of other chemicals.

PMID- 8761353
TI  - Metabolism of [ring-U-14C] agaritine by precision-cut rat, mouse and human liver
      and lung slices.
AB  - Agaritine [(beta-N-[gamma-L(+)glutamyl]-4-hydroxymethylphenylhydrazine] is
      present in the common cultivated mushroom Agaricus bisporus and several agaritine
      derivatives have been shown to produce tumours in experimental animals. In this
      investigation the metabolism of [ring-U-14C]agaritine has been studied in
      precision-cut rat, mouse and human liver slices and in precision-cut rat and
      mouse lung slices. To confirm the functional viability of the tissue slice
      preparations, the metabolism of 7-ethoxycoumarin was also studied. Liver and lung
      slices from all species metabolized 50 microM 7-ethoxycoumarin to 7
      hydroxycoumarin, which was conjugated with D-glucuronic acid and sulfate.
      Incubation of rat, mouse and human liver slices, and rat and mouse lung slices
      with 25 microM [14C]agaritine resulted in a time-dependent formation of
      metabolite(s), which bound covalently to tissue slice proteins. Agaritine
      metabolite covalent binding was greater in mouse liver than in rat and human
      liver slices and was greater in mouse lung than in rat lung slices. No
      correlation was observed between agaritine metabolite covalent binding and tissue
      slice gamma-glutamyltransferase activity. Additional studies with mouse liver
      slices showed that [14C]agaritine was also metabolized to a number of unknown
      polar metabolites. These results demonstrate that agaritine can be metabolized by
      enzymes present in mammalian liver and lung.

PMID- 8761354
TI  - Cadmium and atherosclerosis in the rabbit: reduced atherogenesis by superseding
      of iron?
AB  - This study evaluated the effect of dietary cadmium (Cd) on atherosclerosis in the
      rabbit. Cholesterol was added to the diet to initiate and/or accelerate
      atherogenesis. Cd was added to the diet at two dose levels. Uptake of Cd was 55
      micro gram/kg body weight (BW)/day at the low dose level and 1350 micrograms/ kg
      BW/day at the high dose level. Five groups of rabbits were fed five different
      diets for 9 months: (1) basal diet without additional constituents; (2)
      background diet, which was basal diet to which cholesterol had been added; (3)
      the low-dose level Cd diet, which was background diet to which 2 mg Cd/kg had
      been added; (4) high-dose level Cd diet, which was background diet to which 50 mg
      Cd/kg had been added; and (5) basal diet to which 50 mg Cd/kg had been added.
      Dietary cholesterol increased blood total leucocyte count, serum and liver total
      cholesterol concentrations, serum total bilirubin concentration, low-density
      lipoprotein vitamin E concentration and induction of atherosclerotic plaques in
      the aorta and coronary arteries. Cd in the diet increased liver and kidney Cd
      concentrations in a dose-dependent way, decreased prothrombin time and
      temporarily increased urea and creatinine clearances. Slight kidney damage was
      induced by Cd only in animals fed the high-dose level Cd diet (with or without
      cholesterol). Dietary Cd partly counteracted the dietary cholesterol-induced
      increases of serum and liver total cholesterol concentrations, and tended to
      reduce plaque formation in the aorta. Dietary Cd in rabbits fed cholesterol
      containing diets influenced cholesterol metabolism and tended to decrease
      atherosclerosis in a dose-related fashion. This is in contrast with limited
      epidemiological human data. Dietary Cd also decreased serum ferritin
      concentration and increased serum transferrin concentration. Free iron
      concentration is associated with myocardial infarction in man and augments the
      development of atherosclerosis in rabbits. It is concluded that the observed
      reduction in atherogenesis is related to dietary Cd-induced changes in
      cholesterol metabolism, increased rheology of blood and/or, most likely, reduced
      free iron concentration.

PMID- 8761355
TI  - Comparative subchronic toxicity studies of nixtamalized and water-extracted
      Fusarium moniliforme culture material.
AB  - Fumonisins are mycotoxins produced by Fusarium moniliforme, F. proliferatum and
      other Fusarium species, which are commonly found on corn, cause a variety of
      species-specific toxicoses, and have been linked to human oesophageal cancer in
      areas of southern Africa and China where corn is a dietary staple. The effect of
      nixtamalization, the process by which masa flour is produced by alkaline
      hydrolysis of corn, on the organ-specific toxicity of F. moniliforme culture
      material containing fumonisin B1 (FB1) was studied and the effectiveness of
      nixtamalization and water extraction for detoxifying culture material was
      compared. Male rats (n = 10/group) were fed diets containing 5% culture material
      equivalent weights of nixtamalized culture material (NX diet) providing 58 ppm
      hydrolysed FB1 but no FB1, water-extracted culture material (WE diet) providing 8
      ppm FB1, or untreated culture material (CM diet) providing 71 ppm FB1 for 4 wk.
      An additional control group was fed a diet containing sound seed corn. Serum
      chemical and histopathological findings confirmed that the nixtamalized culture
      material was hepatotoxic and nephrotoxic. Hepatopathy was found in all rats fed
      the NX or CM diets. The lesions were qualitatively similar in these two groups,
      but were noticeably less severe in rats fed the NX diet. In contrast, only one
      rat fed the WE diet exhibited mild hepatopathy. Mild-to-moderate nephropathy
      resembling that induced by FB1 was found in all rats fed the NX, WE or CM diet.
      Thus, the organ-specific effects of nixtamalized culture material, containing no
      detectable FB1, were similar to those of the FB1-containing diet prepared from
      untreated culture material. Furthermore, nixtamalization was not as effective as
      water extraction as a detoxification method.

PMID- 8761356
TI  - An evaluation of genotoxicity tests with Musk ketone.
AB  - Musk ketone, a synthetic musk fragrance ingredient that has been found in river
      water, fish and breast milk, was evaluated for potential genotoxicity in a
      battery of short-term tests. The mouse lymphoma assay was conducted at musk
      ketone concentrations ranging from 700 to 4000 micrograms/ml and 2.0 to 35
      micrograms/ml in the absence and presence of rat liver S-9, respectively. No
      increased mutant frequencies were noted. An in vitro cytogenetics assay in
      Chinese hamster ovary cells was conducted at musk ketone concentrations ranging
      from 4.3 to 34 micrograms/ml and 1.25 to 10 micrograms/ml in the absence and
      presence of rat liver S-9, respectively. On the basis of the non-reproducibility
      of a statistically significant increase at a single concentration and no
      increases in other test systems, musk ketone was concluded to be negative for
      chromosome aberrations. An in vitro unscheduled DNA synthesis (UDS) assay was
      conducted in primary rat hepatocytes at musk ketone concentrations between 0.5
      and 5.0 micrograms and 50 micrograms/ml. No increases in net nuclear grain counts
      were noted. Musk ketone did not show genotoxic potential based on the negative
      results in the mouse lymphoma, in vitro cytogenetics and in vitro UDS assays.

PMID- 8761357
TI  - Safety evaluation of perfluoropolyethers, liquid polymers used in barrier creams
      and other skin-care products.
AB  - Fomblin HC products are a 'family' of high-purity perfluoropolyethers
      manufactured for barrier cream and other personal care applications which involve
      direct application to the skin. To confirm the safety of such use, representative
      Fomblin HC products were tested in experimental animals for acute toxicity,
      primary and repeated insult irritancy, sensitization and photosensitization,
      subacute oral toxicity and comedogenicity; mutagenicity was examined in vitro,
      and irritancy or sensitization was also investigated on human skin (in patch
      tests with volunteers). A high molecular weight Fomblin HC only was tested in
      rats for subacute oral toxicity and in man for dermal effects. Single oral doses
      of 15 g/kg body weight were without evident toxicity to rats, as were single
      dermal applications or an ip injection at 5 g/kg. No primary irritant action was
      seen in rabbits or man, and similarly there was no evidence of skin sensitization
      or photosensitization in guinea pigs, or sensitization in man. No mutagenic
      action on Salmonella strains of tester bacteria was seen. In repeat dose
      irritancy or oral toxicity tests in rabbits or rats, no adverse effects of
      Fomblin HC products were noted; in particular, daily oral administration (1000
      mg/kg/day) to rats over 28 days produced no significant reaction. No comedogenic
      action was found. From the known chemistry of the perfluoropolyethers, the test
      programme reported here and the limited published data, it is concluded that the
      intended use of Fomblin HC products in formulations applied to human skin has a
      high margin of safety.

PMID- 8761358
TI  - Test guidelines for assessment of skin compatibility of cosmetic finished
      products in man. Task Force of COLIPA.

PMID- 8761359
TI  - Comments on the pathogenesis of muscarinic agonist-induced corneal opacities in
      rats.

PMID- 8761360
TI  - Post-operative radiotherapy in non-small-cell lung cancer: more questions than
      answers.

PMID- 8761361
TI  - Meta-analyses of randomised trials: when the whole is more than just the sum of
      the parts.

PMID- 8761362
TI  - Selection of a subpopulation with fewer DNA topoisomerase II alpha gene copies in
      a doxorubicin-resistant cell line panel.
AB  - A panel of doxorubicin-resistant sublines of the human small-cell lung carcinoma
      cell line GLC4 displays decreasing DNA topoisomerase II alpha (TopoII alpha) mRNA
      levels with increasing resistance. In the present study we describe how this
      decrease may be regulated. No significant differences in TopoII alpha mRNA
      stability or gene arrangement were found, using mRNA slot-blotting and Southern
      blotting, in the most resistant cell line compared with the parental cell line.
      To investigate if TopoII alpha gene copy loss contributed to the mRNA decrease,
      fluorescence in situ hybridisation using a TopoII alpha-specific probe was
      performed. During doxorubicin resistance development, the composition of the
      population in each cell line shifted with increasing resistance, from a
      population in which most cells contain three TopoII alpha gene copies (GLC4) to a
      population in which most cells contain only two copies. A partial revertant of
      the most resistant cell line displayed a shift back to the original situation. We
      conclude that the TopoII alpha gene copy number decrease per cell line is in good
      agreement with the decreased TopoII alpha mRNA and protein levels, and TopoII
      activity levels in these cell lines which were described previously.

PMID- 8761363
TI  - Variation in topoisomerase I gene copy number as a mechanism for intrinsic drug
      sensitivity.
AB  - DNA topoisomerase I (topo I) is the principle target for camptothecin and its
      derivatives such as SN38. Levels of topo I expression vary widely between and
      within tumour types and the basis for this is poorly understood. We have used
      fluorescence in situ hybridisation to detect the topo I locus in a panel of
      breast and colon cancer cell lines. This approach has identified a range of topo
      I gene copies from 1 to 6 between the cell lines as a result of DNA
      amplification, polysomy and isochromosome formation. Topo I gene copy number was
      highly correlated with topo I expression, (rs = 0.92), and inversely correlated
      to sensitivity to a 1 h exposure to SN38 (rs = -0.904). This illustrates the
      significant impact of altered topo I gene copy number on intrinsic drug
      sensitivity and influences potential mechanisms for acquisition of drug
      resistance.

PMID- 8761364
TI  - Radioimmunotherapy of colorectal carcinoma xenografts in nude mice with yttrium
      90 A33 IgG and Tri-Fab (TFM).
AB  - The monoclonal antibody A33 recognises a tumour-associated antigen on human
      colorectal carcinoma, and has undergone preliminary evaluation in the clinic
      where selective localisation to hepatic metastases has been demonstrated [Welt et
      al. (1994) J. Clin. Oncol. 12, 1561-1571]. A33 and an A33 tri-fab fragment (TFM)
      were labelled with 90Y via a stable macrocyclic ligand for biodistribution and
      therapy studies in nude mice bearing SW1222 colon carcinoma xenografts.
      Biodistribution studies demonstrated tumour localisation for both A33 IgG and TFM
      with low bone, liver and kidney levels. Clearance of TFM from the blood was much
      faster than IgG and this led to lower tumour accumulation for TFM but superior
      tumour-blood ratios. The maximum per cent injected dose per g localised to tumour
      was 35.9% +/- 5.3% for A33 IgG and 12.9% +/- 4.6% for A33 TFM with tumour-blood
      ratios at 48 h after administration of 5.6 +/- 1.8 and 29.2 +/- 9.8 respectively.
      Autoradiography studies with 125I-labelled A33 IgG and TFM demonstrated a
      homogeneous distribution within tumour tissue which was not observed with other
      anti-colorectal tumour antibodies. TFM penetrated into the tumour tissue more
      rapidly than IgG. In therapy studies, a single dose of 90Y-A33 IgG (250 microCi
      per mouse) or 90Y-A33 TFM (300 microCi per mouse) led to complete regression of 2
      week-old tumour xenografts with long-term tumour-free survivors. A transient drop
      in white blood cell count was observed with both IgG and TFM but was
      significantly more pronounced with IgG. The cell count fell to 8.4% of control
      for IgG, whereas with TFM cell counts fell to 51% of control before recovery.
      These results indicate that the more rapid blood clearance of 90Y-TFM confers
      reduced toxicity compared with 90Y-IgG although similar therapeutic effects are
      achieved. When the dose of 90Y-IgG was adjusted to give the same dose to tumour
      achieved with 300 microCi 90Y-TFM, a lesser therapeutic effect was observed. This
      may be owing to more rapid tumour penetration achieved with TFM. Both A33 IgG and
      TFM demonstrated potent anti-tumour effects against human tumour xenografts in
      this mouse model system. The stability of these 90Y-labelled conjugates and their
      effective tumour penetration are promising for the development of humanised
      reagents for clinical studies.

PMID- 8761365
TI  - Receptor-mediated uptake of low-density lipoprotein by B16 melanoma cells in
      vitro and in vivo in mice.
AB  - Selective delivery of cytotoxic anti-neoplastic drugs can diminish the severe
      side-effects associated with these drugs. Many malignant tumours express high
      levels of low-density lipoprotein (LDL) receptors on their membranes. Therefore,
      LDL may be used as a carrier to obtain selective delivery of anti-neoplastic
      drugs to tumours. The present study was performed to investigate the feasibility
      of the murine B16 tumour/mouse model for the evaluation of LDL-mediated tumour
      therapy. LDL binds with high affinity to LDL receptors on cultured B16 cells (Kd,
      5.9 +/- 2.3 micrograms ml-1; Bmax 206 +/- 23 ng LDL mg-1 cell protein). After
      binding and internalisation, LDL was very efficiently degraded: 724 +/- 19 ng LDL
      mg-1 cell protein h-1. Chloroquine and ammonium chloride completely inhibited the
      degradation of LDL by the B16 cells, indicating involvement of lysosomes. LDL
      receptors were down-regulated by 70% after preincubation of B16 cells with 300
      micrograms ml-1 LDL, indicating that their expression is regulated by
      intracellular cholesterol. To evaluate the uptake of LDL by the B16 tumour in
      vivo, tissue distribution studies were performed in C57/B1 mice inoculated with
      B16 tumours. For these experiments, LDL was radiolabelled with tyramine
      cellobiose, a non-degradable label, which is retained in cells after uptake. At
      24 h after injection of LDL, the liver, adrenals and the spleen were found to be
      the major organs involved in LDL uptake, with tissue-serum (T/S) ratios of 0.82
      +/- 0.08, 1.17 +/- 0.20 and 0.69 +/- 0.08 respectively. Of all the other tissues,
      the tumour showed the highest uptake of LDL (T/S ratio of 0.40 +/- 0.07). A large
      part of the LDL uptake was receptor mediated, as the uptake of methylated LDL was
      much lower. Although the LDL uptake by the liver, spleen and adrenals is higher
      than that by the tumour, the LDL receptor-mediated uptake by these organs may be
      selectively down-regulated by methods that do not affect the expression of LDL
      receptors on tumour cells. It is concluded that the B16 tumour-bearing mouse
      constitutes a good model to evaluate the effectiveness of LDL-mediated delivery
      of cytotoxic (pro)drugs to tumours in vivo.

PMID- 8761366
TI  - Reduction of interstitial fluid pressure after TNF-alpha treatment of three human
      melanoma xenografts.
AB  - Tumour necrosis factor-alpha (TNF-alpha) reduced the interstitial fluid pressure
      (IFP) to 54-64% (P < 0.05) and the mean arterial blood pressure (MABP) to 70% (P
      < 0.01) of control values after 5 h in three human melanoma tumour lines
      transplanted to nude mice.

PMID- 8761367
TI  - Therapeutic activity of CPT-11, a DNA-topoisomerase I inhibitor, against
      peripheral primitive neuroectodermal tumour and neuroblastoma xenografts.
AB  - The anti-tumour activity of CPT-11, a topoisomerase I inhibitor, was evaluated in
      four human neural-crest-derived paediatric tumour xenografts; one peripheral
      primitive neuroectodermal tumour (pPNET) (SK-N-MC) and three neuroblastomas. Two
      models, SK-N-MC and IGR-N835, were established in athymic mice from a previously
      established in vitro cell line. Two new neuroblastoma xenograft models, IGR-NB3
      and IGR-NB8, were derived from previously untreated non-metastatic
      neuroblastomas. They exhibited the classic histological features of immature
      neuroblastoma along with N-myc amplification, paradiploidy, chromosome 1p
      deletions and overexpression of the human mdr 1 gene. These tumour markers have
      been shown to be poor prognostic factors in children treated for neuroblastoma.
      CPT-11 was tested against advanced stage subcutaneous tumours. CPT-11 was
      administered i.v. using an intermittent (q4d x 3) and a daily x 5 schedule. The
      optimal dosage and schedule was 40 mg kg-1 daily for 5 days. At this highest non
      toxic dose, CPT-11 induced 100% tumour-free survivors on day 121 in mice bearing
      the pPNET SK-N-MC xenograft. For the three neuroblastoma xenografts, 38-100%
      complete tumour regressions were observed with a tumour growth delay from 38 to
      42 days, and anti-tumour activity was clearly sustained at a lower dosage (27 mg
      kg-1 day-1). The efficacy of five anti-cancer drugs commonly used in paediatric
      oncology or in clinical development was evaluated against SK-N-MC and IGR-N835.
      The sensitivity of these two xenografts to cyclophosphamide, thiotepa and
      cisplatin was of the same order of magnitude as that of CPT-11, but they were
      refractory to etoposide and taxol. In conclusion, CPT-11 demonstrated significant
      activity against pPNET and neuroblastoma xenografts. Further clinical development
      of CPT-11 in paediatric oncology is warranted.

PMID- 8761368
TI  - Enhancement of sensitivity of human lung adenocarcinoma cells to growth
      inhibitory activity of interferon alpha by differentiation-inducing agents.
AB  - A low concentration of differentiation inducers such as dimethylsulphoxide
      (DMSO), sodium butyrate, hexamethylene bisacetamide and sodium phenylacetate
      greatly enhanced the antiproliferative effect in vitro and in vivo of interferon
      alpha (IFN-alpha) to several human lung adenocarcinoma cells. The agents induced
      morphological changes in the adenocarcinoma cells and the agents together with
      IFN-alpha-induced alkaline phosphatase activity, which is a typical marker of
      type II pneumocyte maturation. To understand the mechanism of the DMSO-enhanced
      interferon sensitivity, we examined the effect of DMSO on high-affinity IFN-alpha
      receptor and interferon-stimulated promoter-binding factors. The lung
      adenocarcinoma cells were not impaired in IFN-alpha receptor and interferon
      stimulated gene transactivation factor 3 (ISGF-3). Our data suggest that the
      enhancement of interferon sensitivity in the lung adenocarcinoma cells acts
      downstream of the activation of ISGF-3.

PMID- 8761369
TI  - TP53 mutation analyses on breast carcinomas: a study of paraffin-embedded
      archival material.
AB  - The aim of this investigation was to examine the possibility of analysing TP53
      mutations in archival paraffin-embedded material with the constant denaturant gel
      electrophoresis (CDGE) method. We extracted DNA from 193 archival primary breast
      carcinoma samples, diagnosed in 1981-83; further analysis was possible for 186 of
      these. TP53 mutations in exons 5-8 were detected with CDGE in 30 samples (16.1%)
      and 17 of these mutations were confirmed by sequencing. Immunohistochemistry
      demonstrated TP53 nuclear accumulation in 58 tumours (31%). A strong association
      between the presence of TP53 mutations and TP53 immunostaining was observed (P <
      0.001). Our mutation and immunohistochemistry results are in agreement with other
      findings based on fresh tumour tissue. TP53 abnormalities were significantly
      related to high S-phase fraction, low oestrogen receptor (ER) content and high
      tumour grade. Survival of patients with TP53 abnormalities, in the group as a
      whole, did not differ from patients with normal TP53. Our study did, however,
      show that patients with abnormal TP53 had a significantly shorter post-recurrence
      survival (P = 0.005) than patients with normal TP53.

PMID- 8761370
TI  - Overexpression of p53 protein is an independent prognostic indicator in human
      endometrial carcinoma.
AB  - The important role of the p53 gene in tumour progression and cellular response to
      DNA damage has prompted investigation of the clinical significance of alterations
      to this gene. We examined both p53 overexpression and mutation of the gene in
      endometrial carcinoma in order to evaluate the prognostic significance of these
      changes. Of 122 endometrial carcinomas, 33 (27%) showed overexpression of p53 in
      the nucleus and 66 (54%) in the cytoplasm. Mutation in the p53 gene was found in
      16 (13%) cases but showed no significant association with patient survival.
      Nuclear p53 overexpression was associated with poor survival (48% vs 80% alive in
      negative tumours 5 years post operatively, P < 0.001). In contrast, cytoplasmic
      p53 overexpression was associated with better survival (85% vs 55%, P < 0.001).
      When patients were separated into prognostic subgroups according to established
      clinical markers, these associations remained significant within most subgroups
      examined. In multivariate analysis adjusted for surgical stage, histological
      grade and type and vascular invasion, both nuclear p53 overexpression [hazard
      ratio 4.9 (95% CI 1.3-17.6). P = 0.016] and cytoplasmic overexpression [0.25
      (0.06-0.98), P = 0.047] were independent prognostic factors. Immunohistochemical
      assessment of p53 overexpression in the nucleus and cytoplasm could provide
      useful prognostic information for the management of patients with endometrial
      cancer.

PMID- 8761371
TI  - Screening for prostate cancer using serum prostate-specific antigen: a
      randomised, population-based pilot study in Finland.
AB  - The possibility of screening the general population for prostate cancer using
      serum prostate-specific antigen (PSA) level (alone or in combination with other
      tests) as screening test has recently been discussed. A number of studies are on
      the way, but the published reports have almost exclusively been based on men
      volunteering for screening. We assessed the feasibility of a screening study
      based on men identified from a central population registry. A random sample of
      600 men in the age groups 55, 60 and 65 years was identified from the Finnish
      Population Registry as the study population. Half of them were randomised to the
      intervention group and an invitation to participate was sent to them. The
      participation rate was 77% (230 out of 300). Twenty-five men had a serum PSA
      concentration of 4.0 micrograms l-1 or above and were invited for further
      examination including digital rectal examination, transrectal ultrasound and
      transrectal Tru-cut biopsies (directed and/or random). Six cases of cancer were
      detected among the 230 participating men, which corresponds to a detection rate
      of 2.6% and a positive predictive value of 24%. The number of cases detected is
      equivalent to the expected number of prostate cancer cases during a 10 year
      follow-up in this population. The ratio of free to total PSA was also measured
      and a cut-off level of 0.20 was chosen. Its use as an additional criterion of the
      screening test would have decreased the prevalence of false-positive screening
      tests from 8% (19 of 230) to 3% (7 of 230) at a cost of missing one of the six
      cancers compared with serum total PSA concentration alone. Of the six cancers,
      five were clinically regarded as localised and locally confined disease was
      confirmed pathologically in four of them. In conclusion, a population-based study
      in Finland seems feasible and the properties of the PSA test can be regarded as
      suitable for a randomised screening study. Thus, all prerequisites for a
      multicentre study, which is planned, seem to exist.

PMID- 8761372
TI  - A retrospective study of high mobility group protein I(Y) as progression marker
      for prostate cancer determined by in situ hybridization.
AB  - In a previous study using RNA in situ hybridisation (RISH), we found a
      significant correlation between high mobility group protein I/Y, [HMG-I(Y)] mRNA
      expression and tumour stage and grade in prostate cancer patients, suggesting
      that HMG-I(Y) might be a potential prognostic marker in prostate cancer. However,
      our clinical follow-up was limited because cryopreserved material was used.
      Assessing the potential prognostic value of this molecule is of importance
      because the clinical course of prostate cancer patients remains unpredictable.
      Here we describe our results on paraffin-embedded archival material from a group
      of 102 patients undergoing radical prostatectomy. These were evaluated for the
      presence of HMG-I(Y) using RISH, and a follow-up of 12-92 months (average 53
      months) was available. In 2 of 14 prostate cancers in which the predominant
      histological pattern was of Gleason grade 1-2, a high HMG-I(Y) expression was
      observed, whereas in 19 of 23 Gleason grade 3, and 34 of 35 Gleason grade 4-5
      tumours, high HMG-I(Y) mRNA levels were detected (chi-square = 38.78, P <
      0.0001). Moreover, of tumours that expressed high HMG-I(Y) levels, 25% were organ
      confined (T1-2), in contrast to 74.5% of the invading tumours (T3, chi-square =
      15.8, P < 0.001). Furthermore, 87% of recurrent tumours showed high HMG-I(Y)
      expression. However, a multivariate regression analysis including Gleason grade,
      clinical tumour stage, HMG-I(Y) expression and prostate-specific antigen (PSA)
      levels showed Gleason grade as the most accurate predictor of progression. High
      HMG-I(Y) levels measured by RISH were indicative of a worse prognosis, albeit
      that additional value over the more subjective grading methods was not evident.

PMID- 8761373
TI  - Cell adhesion molecules in bladder cancer: soluble serum E-cadherin correlates
      with predictors of recurrence.
AB  - Sera from 40 patients with newly diagnosed bladder cancer (28 superficial tumours
      (pTa and pT1) and 12 muscle-invasive tumours) were assessed by enzyme-linked
      immunosorbent assay (ELISA) to determine the concentrations of soluble E-cadherin
      (sE-cadherin), soluble E-selectin (sE-selectin), soluble vascular cell adhesion
      molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1).
      Corresponding frozen sections of primary tumour were analysed for E-cadherin
      expression using the monoclonal antibody, HECD-1 and standard
      immunohistochemistry. Patients with bladder cancer had significantly higher
      concentrations of sE-cadherin compared with a control group (P = 0.017). No
      difference was found between the two groups with regard to sE-selection (P =
      0.403), sVCAM-1 (P = 0.942) and sICAM-1 (P = 0.092). High levels of sE-cadherin
      were related to poor histological grade (P = 0.009), number of superficial
      tumours at presentation (P = 0.008) and a positive 3 month check cytoscopy in
      superficial disease (P = 0.036). Abnormal E-cadherin expression was associated
      with increasing tumour stage (P = 0.009) and grade (P = 0.03). There was no
      correlation between high levels of soluble E-cadherin in sera and abnormal E
      cadherin expression by the tumour (P = 0.077). Elevated levels of sE-cadherin are
      found in sera of patients with bladder cancer and correlate with known prognostic
      factors.

PMID- 8761374
TI  - RET activation in adult and childhood papillary thyroid carcinoma using a reverse
      transcriptase-n-polymerase chain reaction approach on archival-nested material.
AB  - Activation of the RET tyrosine kinase domain occurs in a proportion of thyroid
      papillary carcinomas. Three chromosomal rearrangements have been described, of
      which PTC1 is the commonest. Wide differences (2.5-25%) in frequency of PTC1 in
      different populations have been reported; it is not clear whether these are due
      to environmental factors, racial differences or technical reasons. We have
      developed a simple and rapid reverse transcriptase nested polymerase chain
      reaction (RT-nPCR) method enabling the detection of gene expression from single 5
      microns sections of formalin-fixed paraffin wax-embedded archival material. We
      have applied this approach to detect expression of the RET tyrosine kinase
      domain, allowing identification of RET activation resulting from any
      rearrangement, whether characterised or not, or from overexpression. A
      retrospective study was performed on 22 adult and 21 childhood papillary
      carcinomas. Thirteen of 22 (59%) adult and 10 of 21 (48%) childhood carcinomas
      showed evidence of RET activation, demonstrating a major role for the RET
      oncogene in UK thyroid papillary carcinogenesis. This study also shows a similar
      frequency of RET activation in both children and adults. The use of a technique
      that allows reliable amplification of RNA from archival material, using primers
      chosen in different exons so that amplified products are readily distinguished
      from genomic DNA, will allow correlation of translocations and chromosomal
      rearrangements with a variety of specific tumour types.

PMID- 8761375
TI  - Ormaplatin resistance is associated with decreased accumulation of its platinum
      (II) analogue, dichloro(D,L-trans)1,2-diaminocyclohexaneplatinum (II).
AB  - Ormaplatin (also known as tetraplatin) is a platinum-containing analogue which
      has recently undergone clinical trials. Ormaplatin may undergo conversion to
      dichloro(D,L-trans)-1,2-diaminocyclohexaneplatinum(II) [P1Cl2(trans-dach)]. The
      cisplatin-resistant murine lymphoma cell lines E8 and E5, were found to be cross
      resistant to ormaplatin and PtCl2(trans-dach). We found an inverse rank
      correlation between drug resistance and drug accumulation for PtCl2(trans-dach)
      similar to our previous findings with cisplatin; however, accumulation of
      ormaplatin in the resistant cells was increased. Ormaplatin cytotoxicity appears
      to result primarily from extracellular conversion to PtCl2(trans-dach), since
      ormaplatin cytotoxicity was decreased under conditions where extracellular
      conversion to PtCl2(trans-dach) was minimised. Co-incubation with different
      inhibitors of energy metabolism resulted in a 65-70% increase in PtCl2(trans
      dach) accumulation in the parental cell line R1.1 and a 113-307% increase in the
      resistant cell line E5 which suggests that the decrease in accumulation in E5 may
      be at least partly energy dependent. We conclude from these findings that cross
      resistance to ormaplatin is associated with an energy-dependent decreased
      accumulation of PtCl2(trans-dach) in these cisplatin-resistant cell lines.

PMID- 8761376
TI  - Distribution of neocarzinostatin conjugated to biotinylated chimeric monoclonal
      antibody Fab fragments after administration of avidin.
AB  - We have developed chimeric Fab fragments of MAb A7 (chA7Fab) and have reported on
      their potential usefulness as a carrier of neocarzinostatin (NCS). However, a
      large amount of chA7Fab accumulates in the kidneys which might cause renal
      failure. This was one of the major side-effects of the chA7Fab-NCS
      immunoconjugate administered to humans. To decrease the kidney accumulation of
      chA7Fab, chA7Fab was biotinylated and administered with a subsequent injection of
      avidin to nude mice with pancreatic cancer. The accumulation of biotinylated
      chA7Fab in the blood and the kidneys decreased significantly after the injection
      of avidin. In a separate experiment with biotinylated chA7Fab-NCS, the blood and
      kidney accumulation decreased significantly after the injection of avidin. These
      findings suggest that the injection of biotinylated chA7Fab complexed with NCS
      followed by avidin may be safer and may permit the administration of larger doses
      of NCS without the subsequent development of renal failure.

PMID- 8761377
TI  - Treatment of experimental mouse bladder tumour by LPS-induced epithelial cell
      shedding.
AB  - The purpose of the present study was to explore the therapeutic potential of
      serial administration of shedding-inducing endotoxin in a mouse tumour bladder
      model. The studies were conducted with two variants derived from the MBT-2 tumour
      namely, T5 and T50, the latter being far more aggressive than the former. It was
      found that T5 tumours responded to intravesical lipopolysaccharides (LPS)
      instillation by a considerable reduction in their pace of growth (P < 0.0001)
      when treatment was initiated 3 days after tumour implantation, but not when
      started after 7 days. The T50 variant did not respond to LPS when treated 3 days
      after implantation, but a considerable reduction in rate of growth occurred when
      treatment was started after 1-2 days. Shedding induced by intravesically
      instilled LPS was found to retard considerably the progression rate of
      experimental bladder tumour.

PMID- 8761378
TI  - Dissociation of thyrotropin receptor function and thyrotropin dependency in rat
      thyroid tumour cell lines derived from FRTL-5.
AB  - Spontaneously transformed somatic thyrocyte mutants, FRTL-5/TA and FRTL-5/TP, are
      thyrotropin (TSH) independent for growth and show loss of the thyroid-specific
      phenotype, with absent thyroglobulin and thyroid peroxidase gene expression. To
      investigate the role of TSH-receptor (TSH-R) activation in rat thyroid growth and
      function, binding of TSH and TSH-induced cAMP production were measured in intact
      cells under identical assay conditions. TSH binding did not differ in terms of
      affinity and receptor number and presence of 5.6 kb and 3.3 kb mRNA rat TSH-R
      transcripts was determined in all variants. By contrast, basal cAMP was 11-fold
      lower in FRTL-5/TA and 6-fold lower in FRTL-5/TP than in wild-type FRTL-5 (1.1 +/
      0.4; P < 0.01). Maximal cAMP production was similar between wild-type and cell
      variants and stimulation by bovine, rat and recombinant human TSH revealed normal
      activation patterns. Therefore, a dissociation was present between the loss of
      TSH control on growth and function, and the presence of a normally functioning
      TSH-R. Subsequent to TSH incubation FRTL-5/TP and FRTL-5/TA cells showed a
      different expression pattern of TSH-R and the proto oncogenes c-myc and fos than
      FRTL-5 wild-type. The data indicated that the cause of the TSH-independency is
      located down-stream of the cAMP cascade, influencing genes that control the
      expression of cell cycle-related proto-oncogenes and thyroid-specific genes.

PMID- 8761379
TI  - Differential effect of polyunsaturated fatty acids on cell proliferation during
      human epithelial in vitro carcinogenesis: involvement of epidermal growth factor
      receptor tyrosine kinase.
AB  - Polyunsaturated fatty acids (PUFAs) have been implicated in tumour development
      and have been shown to influence cell proliferation in vitro. We report here that
      n-3 and n-6 PUFAs at concentration > 10 microM inhibited the proliferation of a
      human kidney epithelial cell line (21HKE), which has retained phenotypic
      characteristics of normal kidney epithelial cells. In contrast, the proliferation
      was stimulated by n-3 and n-6 PUFAs at concentrations < 10 microM under defined
      growth conditions. The stimulatory effect of n-3 and n-6 PUFAs was even more
      profound in the presence of EGF. In human kidney epithelial cell lines reflecting
      different stages of transformation (11HKE and 1THKEras), the stimulatory effect
      was abrogated both in the presence and absence of EGF. Saturated fatty acids did
      not show any stimulatory effect on cell growth. The tyrosine kinase inhibitors
      genistein and tyrphostin-47 inhibited EGF-induced protein tyrosine
      phosphorylation dose-dependently in the 21HKE cells, and abolished the growth
      stimulatory effect of docosahexaenoic acid (DHA). This indicates the involvement
      of EGF receptor tyrosine kinase activity in the observed increase in cell
      proliferation.

PMID- 8761380
TI  - Effect of modulation of the transferrin receptor on gallium-67 uptake and
      cytotoxicity in lymphoma cell lines.
AB  - Gallium-67 is a radionuclide that accumulates in haematological malignancies and
      is used for diagnostic purposes. Uptake of 67Ga into the cell occurs via the
      transferrin receptor, which is differentially expressed during the various cell
      cycle phases. With the aim of selectively increasing 67Ga uptake, we studied
      whether the transferrin receptor (TfR) expression could be modulated in the U937
      and U715 lymphoma cell lines by cytostatic drugs inducing cell cycle phase
      accumulation. We tested clinically relevant drugs such as 1-beta-D
      arabinofuranosylcytosine (Ara-C), hydroxyurea and methotrexate. Cytotoxicity was
      determined by testing the clonogenic capacity of the lymphoma cell lines. All
      three drugs induced an increase in S-phase content, TfR expression and 67Ga
      uptake in U937 and U715 single cells. The combinations of drugs and 67Ga resulted
      in an additive effect on the clonogenic capacity. In U937 spheroids, cultured by
      the fibrin clot technique, we found an accumulation in the S-phase too as well as
      an increase of the transferrin receptor expression after Ara-C preincubation. As
      in single cells 67Ga uptake was increased without synergistic effects on the
      clonogenic capacity. In conclusion, priming with drugs induces increased
      transferrin receptor expression and 67Ga uptake. Inhibition of clonogenic
      capacity was additive rather than synergistic.

PMID- 8761381
TI  - Transcriptional analysis of Epstein-Barr virus gene expression in EBV-positive
      gastric carcinoma: unique viral latency in the tumour cells.
AB  - Although case-oriented evidence for an association of Epstein-Barr virus (EBV)
      with gastric carcinoma has been accumulating recently, the interaction(s) between
      EBV and gastric epithelial cells is/are largely unknown. In this study, we
      examined seven EBV-positive gastric carcinoma tissues for viral gene expression
      at the mRNA level, from which studies on the EBV oncogenicity in human epithelial
      cells will benefit. Reverse transcription-PCR analysis showed that all seven EBV
      positive tumour tissues constitutively expressed EBV nuclear antigen (EBNA) 1
      mRNA, but not EBNA2 mRNA. The EBNA transcription was initiated from one of three
      EBNA promoters, Qp: by contrast, both Cp and Wp were silent, thus resulting in
      the lack of EBNA2 mRNA. Latent membrane protein (LMP) 2A mRNA was detected in
      three of seven cases; however, neither LMP1 nor LMP2B mRNA was detected in any of
      the tumours tested. Transcripts from the BamHI-A region of the viral genome were
      detectable in all cases. BZLF1 mRNA and the product, an immediate-early gene for
      EBV replication, was not expressed in any of them, thereby suggesting that the
      tumour cells carried EBV genomes in a tightly latent form. These findings further
      extended our previous data regarding EBV latency in gastric carcinoma cells at
      the protein level, and have affirmed that the programme of viral gene expression
      in the tumour more closely resembles 'latency I' represented by Burkitt's
      lymphoma than 'latency II' represented by the majority of nasopharyngeal
      carcinomas.

PMID- 8761382
TI  - The role of post-operative radiotherapy in non-small-cell lung cancer: a
      multicentre randomised trial in patients with pathologically staged T1-2, N1-2,
      M0 disease. Medical Research Council Lung Cancer Working Party.
AB  - The role of post-operative radiotherapy for patients with non-small-cell lung
      cancer (NSCLC) is unclear despite five previous randomised trials. One deficiency
      with these trials was that they did not include adequate TNM staging, and so the
      present randomised trial was designed to compare surgery alone (S) with surgery
      plus post-operative radiotherapy (SR) in patients with pathologically staged T1
      2, N1-2. M0 NSCLC. Between July 1986 and October 1993, 308 patients (154 S, 154
      SR) were entered from 16 centres in the UK. The median age of the patients was 62
      years, 74% were male, > 85% had normal or near normal levels of general
      condition, activity and breathlessness, 68% had squamous carcinoma, 52% had had a
      pneumonectomy, 63% had N1 disease and 37% N2 disease. SR patients received 40 Gy
      in 15 fractions starting 4-6 weeks post-operatively. Overall there was no
      advantage to either group in terms of survival, although definite local
      recurrence and bony metastases appeared less frequently and later in the SR
      group. In a subgroup analysis, in the N1 group no differences between the
      treatment groups were seen, but in the N2 group SR patients appeared to gain a
      one month survival advantage, delayed time to local recurrence and time to
      appearance of the bone metastases. There is, therefore, no clear indication for
      post-operative radiotherapy in N1 disease, but the question remains unresolved in
      N2 disease.

PMID- 8761383
TI  - A quantitative approach to the distress caused by symptoms in patients treated
      with radical radiotherapy.
AB  - A computerised self-assessment instrument was used to capture data on the
      distress caused by symptoms in 110 patients treated with radical radiotherapy.
      Patients selected symptoms from a list of 34 problems and then quantified the
      distress associated with each problem using a linear Analogue self assessment
      (LASA)-type scale. The test instrument was feasible: 90% of assessments were
      completed in under 14 min. There was a significant increase in tiredness and
      significant decrease in anxiety and worries about the family, during treatment.
      Menopausal symptoms and post-surgical problems were important causes of distress
      in the patients with breast cancer. When the area under the curve method was used
      to quantify distress in the patients with breast cancer, difficulty
      concentrating, pain and sleep disturbances emerged as significantly troublesome
      problems. Computerised self-assessment may have a useful role in quantifying the
      distress caused by treatment with radiotherapy.

PMID- 8761384
TI  - Phase I trial of elactocin.
AB  - Elactocin is a novel anti-tumour antibiotic which has potent activity in vitro
      against a range of tumours. This phase I trial of elactocin identified the dose
      limiting toxicity as profound anorexia and malaise. The schedules used included 1
      h infusion 3 weekly, 24 h infusion 3 weekly, 1 h infusion daily x 5 (3 weekly), 1
      h infusion weekly and finally continuous 5 day intravenous infusion. On all these
      schedules dose-limiting toxicity was the same and as no partial or complete
      responses were identified, we do not recommend that further trials of elactocin
      are performed.

PMID- 8761385
TI  - A multicentre phase II study of docetaxel 75 mg m-2 as first-line chemotherapy
      for patients with advanced breast cancer: report of the Clinical Screening Group
      of the EORTC. European Organization for Research and Treatment of Cancer.
AB  - In this phase II study, 39 women (median age 51 years) with advanced breast
      cancer received docetaxel (75 mg m-2) intravenously over 1 h every 3 weeks as
      first-line chemotherapy for advanced disease, without routine premedication for
      hypersensitivity reactions. In 31 evaluable patients, an overall response rate of
      52% (95% CI 33-70%) was achieved, including a complete response rate of 13%. The
      median time to first response was 12 weeks (range 3-35+), the median duration of
      response was 34 weeks (range 11-42+) and the median time to progression was 24
      weeks (range 0-42+). Docetaxel showed considerable activity in patients with
      visceral involvement (52% response), including lung (67%) and liver (44%)
      metastases. The safety profile was acceptable. Grade 4 neutropenia occurred in
      82% of patients (53% of cycles); febrile neutropenia (grade 4 neutropenia with
      fever > 38 degrees C, requiring antibiotics) occurred in only three (7.7%)
      patients (1.4% of cycles) and none of these required hospitalisation. Acute
      adverse events were generally well tolerated, with only two grade 3 events and no
      grade 4 events reported. Despite no prophylactic premedication, the incidence of
      acute hypersensitivity reactions was only 13%. Fluid retention was widely
      experienced (72% of patients) but was severe in only five (12.8%) patients and
      was the reason for discontinuation of treatment in 16 patients. Nevertheless,
      patients were able to receive a median cumulative dose of approximately 592 mg m
      2 before discontinuing treatment, and the syndrome was slowly reversible after
      treatment withdrawal. In conclusion, docetaxel, even at a dose of 75 mg m-2, is
      confirmed to be an active agent in breast cancer. Compared with an earlier study
      of first-line docetaxel at the usual dose of 100 mg-2, it appears that 75 mg m-2
      produces a lower response rate (52% vs 68%), although this still compares
      favourably with that of doxorubicin monotherapy in a similar patient population
      (43%). This difference is particularly striking in subgroups of patients with
      particularly poor prognostic factors, such as liver metastases or involvement of
      more than two organs. The incidence of fluid retention appears to be similar at
      the two doses and, it is likely that premedication with corticosteroids will be
      preferable to dose reduction for managing this adverse event.

PMID- 8761386
TI  - Adolescent milk, dairy product and fruit consumption and testicular cancer.
AB  - There is an association between dairy product consumption and the incidence of
      testicular cancer in different countries. To test the hypothesis that milk and
      dairy products are risk factors, a case-control study was performed in East
      Anglia, UK. All the cases were men with testicular cancer and for each of the 200
      cases there were four controls, two cancer controls and two population controls.
      The response rate of those eligible subjects who received a questionnaire was:
      cases 73%, cancer controls 65% and population controls 57%. All responding
      subjects completed a dietary questionnaire including questions on current and
      adolescent milk, dairy product and fruit and vegetable consumption. The answers
      were corroborated when possible by the subjects' mothers using a separate
      questionnaire. Cases consumed significantly more milk in adolescence than
      population controls, but this difference did not apply to other dairy products or
      fruit. The consumption of milk by cancer controls was intermediate between cases
      and population controls. Cancer controls with non-epithelial cancers had a milk
      consumption similar to cases, whereas subjects with epithelial cancers had a
      consumption similar to population controls. In a multivariate analysis the odds
      ratio between cases and population controls for the association of undescended
      testis and testicular cancer was 7.19 (95% CI 2.36-21.9) and for each extra
      quarter pint of milk consumed it was 1.39 (95% CI 1.19-1.63).

PMID- 8761387
TI  - A case-control study of cancer of the prostate in Somerset and east Devon.
AB  - A case-control study in Somerset and east Devon was undertaken to investigate
      possible risk factors for prostatic cancer. A total of 159 cases, diagnosed at
      Taunton. Yeovil and Exeter hospitals between May 1989 and May 1991, were
      identified prospectively and interviewed with a structured questionnaire. A total
      of 161 men diagnosed with benign prostatic hypertrophy and 164 non-urological
      hospital controls were given identical questionnaires. The questionnaire covered
      a wide range of factors identified from previous studies, but the central
      hypotheses for this study related to diet (fat and green vegetables), sexual
      activity and farming as an occupation. This study found no association between
      farming and risk of prostatic cancer (odds ratio = 0.74, 95% confidence interval
      0.46-1.18), nor with sexual activity as measured by number of sexual partners
      (chi-squared test for trend P = 0.52). A history of sexually transmitted disease
      was not significantly associated with prostatic cancer, but the numbers involved
      were very small and the odds ratio of 2.06 (0.38-11.2) is consistent with the
      hypothesis. A range of questions aimed at eliciting dietary fat intake produced
      no significant associations, although meat consumption showed increasing risk
      with increasing consumption (test for trend P = 0.005). Increased consumption of
      leafy green vegetables was associated with lower risk, but not significantly so
      (test for trend P = 0.16). As expected with so many factors investigated, some
      statistically significant associations were found, although these can only be
      viewed as hypothesis generating in this context. These included apparent
      protective effects of circumcision and high fish consumption.

PMID- 8761388
TI  - Ocular ultrasound.

PMID- 8761389
TI  - Gadolinium-DTPA enhanced echoplanar MR imaging of the liver: preliminary
      observations.
AB  - This study describes our preliminary experience with dynamic gadopentetate
      dimeglumine enhanced echoplaner MR imaging (EPI) in fifteen patients with focal
      liver lesions. Lesion diagnosis was established by histology (n = 3) or typical
      imaging characteristics (exclusive of the EPI study) combined with clinical
      follow up (n = 12). Dynamic gadopentetate dimeglumine (0.1 mmol/kg) enhanced MR
      imaging was performed on a commercially available 1.5 T EPI equipped MR system
      using a single-excitation fat-suppressed inversion recovery pulse sequence. The
      choice of an IR sequence allowed nulling of the lesion signal by varying T1 prior
      to enhancement creating the optimal conditions for qualitative inspection of the
      enhancement profile. Intershot delay (defined as TR) ranged from 1-5s. Image
      analysis was performed qualitatively by two radiologists. Benign and malignant
      lesions displayed temporal enhancement profiles compatible with characteristic
      findings expected with conventional imaging modalities. Further refinements in
      our technique and expanded system capabilities will allow dynamic imaging of the
      entire liver with improved temporal resolution over conventional sequences.

PMID- 8761390
TI  - Endorectal MRI using a 0.5 T mid-field system in the staging of localized
      prostate cancer.
AB  - The accuracy of high field, endorectal MRI in the staging of localized prostate
      cancer has been the focus of many previous reports. We present our findings with
      a mid-field magnet. Twenty-two patients with clinically localized prostate cancer
      were prospectively staged with endorectal MRI using a 0.5 T magnet. All patients
      subsequently underwent radical prostatectomy and the results of pre-operative MRI
      staging were compared with the histological findings. The overall staging
      accuracy for mid-field, endorectal MRI was 77% (17/22). The sensitivity and
      specificity were 50% (7/14) and 100% (8/8), for diagnosing capsular penetration
      and 100% (4/4) and 94% (17/18), for seminal vesicle invasion. This study
      demonstrates that as a result of recent developments in mid-field MRI design it
      is now possible to use these MR systems in conjunction with an endorectal probe
      to stage localized prostate cancer and that the accuracy is comparable to
      previous reports using high-field magnets.

PMID- 8761391
TI  - Fat suppressed contrast enhanced MR imaging in the assessment of sacroiliitis.
AB  - OBJECTIVE: To investigate the role of Gd-DTPA enhancement in the diagnosis of
      sacroiliitis. PATIENTS AND METHODS: Fifteen patients with definite sacroiliitis,
      five subjects from an 'equivocal group', and five controls were imaged with Fast
      STIR, T1-weighted with fat suppression (T1FS) before and after Gd-DTPA. The
      'equivocal group' included those who had abnormally high signal on Fast STIR
      images only suggestive of early sacroiliitis. The enhancement factor was
      calculated for T1FS images. Patients graded their symptoms at the time of MR
      imaging. The extent of abnormal enhancement was defined as none, local, or
      extensive. RESULTS: Fourteen patients with definite sacroiliitis and one patient
      from the 'equivocal group' demonstrated abnormal Gd-DTPA enhancement of their
      sacroiliac joints or adjacent subchondral marrow. Correlation between the
      patients' symptoms and maximal enhancement of the subchondral marrow was r =
      0.75, P < 0.01, and the extent of abnormal enhancement was r = 0.68, P < 0.01.
      CONCLUSION: Fat suppressed Gd-DTPA or Fast STIR images can be used to assess
      disease activity in patients with sacroiliitis. Abnormal Gd-DTPA enhancement in
      the 'equivocal group' is important additional evidence suggesting the diagnosis
      of early sacroiliitis.

PMID- 8761392
TI  - Endosonographic assessment of postpartum anal sphincter injury using a 120 degree
      sector scanner.
AB  - Obstetric injury is the principal cause of faecal incontinence in women. We
      describe use of a 120 degrees sector ultrasound probe to assess integrity of the
      anal sphincters in primigravid women. Eighty-eight women were successfully
      studied 6 weeks following vaginal delivery. Anal vector manometry and pudendal
      nerve studies were abnormal in 54 (61%), of whom 41 (71%) were symptomatic
      (urgency of defaecation, incontinence to flatus or faeces). The sonographic
      pattern of the anal sphincters described with a 360 degrees probe was reproduced.
      Forty-eight abnormal scans were reported by two radiologists with a kappa
      statistic of 0.65. Sphincter defects were found in 11 asymptomatic women. We
      conclude that anal endosonography has an important role screening for and
      diagnosis of postpartum anal sphincter defects. Use of a 120 degrees sector
      ultrasound probe may prove a cost-effective means of increasing the availability
      of this technique.

PMID- 8761393
TI  - The impact of core-biopsy on pre-operative diagnosis rate of screen detected
      breast cancers.
AB  - The UK breast screening Surgical Quality Assurance guidelines suggest a target
      for pre-operative diagnosis of screen detected cancer of over 70%. Core biopsy
      was introduced in our breast screening assessment clinics in April 1994 and this
      study reports the impact of introducing core biopsy on the pre-operative
      diagnosis rate. Between April 1994 and March 1995, 100 cancers were detected.
      Results of fine needle aspiration cytology and core biopsies were studied to
      assess the contribution of each to the pre-operative diagnosis rate of cancer and
      comparison made with results from the previous 2 years. After introducing core
      biopsy pre-operative diagnosis rates rose from 72% to 90% (P < 0.0002) leading to
      a 64% reduction in diagnostic biopsies for screen detected cancer. Malignant
      results were obtained in 61% of first FNA (similar to previous years) and 74% of
      first core biopsies (combined 87%). Repeat FNA/core diagnosed three further
      cancers increasing the final pre-operative diagnosis rate to 90%. Final
      pathological examination after surgical excision demonstrated an increase in the
      preoperative detection of DCIS from 39% to 82% (P < 0.01) and invasive disease
      from 80% to 92% (P < 0.02). The introduction of core biopsy has significantly
      improved our management of screen detected breast cancer.

PMID- 8761394
TI  - A blinded clinical trial comparing conventional cleansing enema, Pico-salax and
      Golytely for barium enema bowel preparation.
AB  - An evaluator-blinded randomized clinical trial was undertaken to assess the
      effectiveness and patient acceptance of three bowel cleansing regimens:
      conventional cleansing enema, Pico-salax and Golytely. PATIENTS AND METHODS: One
      hundred and fifty patients, referred for barium enema examination, were allocated
      to one of the three regimens. Both the radiographers and the radiologists did not
      know the method of preparation. Radiographers were requested to enter the
      patients' data, the number of bowel openings, the patients' comments of the
      preparation and side effects. Films were reviewed independently by two
      experienced radiologists for the degree of bowel cleanliness and quality of
      barium coating. RESULTS: The mean (standard deviation) of bowel opening frequency
      for the cleansing enema, Pico-Salax and Golytely were 3.6(4.4), 8.3(4.8) and
      7.1(4.2), respectively, with less bowel opening in the cleansing enema. There was
      less nausea associated with the cleansing enema (P = 0.006), more vomiting with
      Golytely (P = 0.008), less abdominal fullness with Pico-salax (P = 0.0006), less
      anorectal irritation with Golytely (P = 0.025), and no difference in the
      abdominal pain amongst three groups. There was no statistically significant
      difference in the number of bowel openings between the groups. Patients found
      that Pico-salax tasted better than Golytely (P = 0.0094) and Golytely was less
      accepted in the amount of fluid intake (P = 0.0018 and P < 0.0002 comparing
      Golytely with the cleansing enema and Pico-salax). Chi-squared testing showed no
      statistically significant difference in bowel cleanliness and quality of barium
      coating among the three preparations. CONCLUSIONS: There was no difference in the
      effectiveness of the three regimens. Pico-salax seems the most acceptable because
      it has the fewest side effects.

PMID- 8761395
TI  - Is the metacarpal index useful in the diagnosis of Marfan syndrome?
AB  - AIM: This study was undertaken to analyse the importance of the Metacarpal Index
      (MCI) in making the diagnosis of Marfan syndrome. PATIENTS AND METHODS: The
      characteristics of 42 patients with Marfan syndrome as defined by strict criteria
      were analysed. Fifty-one consecutive accident and emergency patients comprised
      the control group for the MCI measurements. RESULTS: Using MCI alone four (7.8%)
      of controls had an abnormal MCI, and seven (16.6%) of Marfan patients were
      normal. Thirty-two (76%) of Marfan patients had an abnormal MCI and three (13.4%)
      were equivocal. Using other skeletal parameters (upper segment to lower segment
      ratio, arm span 3 cm or more greater than height, or palate, pectus or scoliosis
      deformity) 40 (95%) of the Marfan group had an abnormality. Other parameters: 18
      (43%) in the Marfan group gave a history of retinal detachment or ectopia lentis.
      Echocardiographic measurements showed aortic root dilatation in 29 (69%) and in
      21 (50%) mitral valve prolapse was found; 37 (88%) had one or other cardiac
      abnormality. Using all parameters excluding MCI: All the patients would still
      have fulfilled the diagnostic criteria for the diagnosis of Marfan syndrome.
      CONCLUSION: The role of the MCI, a radiation dependent and time consuming
      measurement, is probably insignificant in diagnosis of the majority of Marfan
      patients. Combined with clinical measurements, an echocardiogram is probably the
      single most useful investigation, aiding both diagnosis and management.

PMID- 8761396
TI  - Increased reflectivity of the pancreas in rare hereditary pancreatic
      insufficiency syndromes.

PMID- 8761397
TI  - Frequency-filtered image post-processing of digital luminescence radiographs in
      pulmonary nodule imaging.
AB  - AIM: The aim of the study was to optimize unsharp masking image post-processing
      of digital luminescence radiographs (DLR) for the representation of pulmonary
      nodules, and to compare DLR to screen-film radiography at two dose levels.
      PATIENTS AND METHODS: A total of 284 CT-validated pulmonary nodules were
      evaluated. One hundred and forty-nine nodules were exposed with a 200-speed
      screen-film combination (SFC) and 135 nodules with a 400-speed SFC, with
      correspondingly exposed storage phosphor images. The kernal size in digital post
      processing using 'unsharp masking' was varied between S 10 (2.83 mm) and S 70
      (19.80 mm). A total of 11928 individual assessments were obtained from six
      independent observers and evaluated in multifactorial variance analyses. RESULTS:
      The large filter kernels of S 40 and S 70 were on a par with the 200-speed SFC (P
      > 0.05). As the exposure dose was reduced, the quality of the digital image vis-a
      vis the 400-speed SFC improved significantly (P < 0.05). Smaller filter kernels
      (S 10; S 20) producing edge-enhancement processing were significantly inferior to
      the analog image technique in both dose ranges (P < 0.05). CONCLUSIONS: At speed
      class 200, low-frequency emphasizing digital image post-processing with large
      filter kernels are significantly superior to high-frequency emphasizing
      filtrations for the recognition of pulmonary nodules. In the lower dose range DLR
      with large filter kernel unsharp masking processing showed significantly improved
      image quality compared to 400 speed SFC for the detection of pulmonary nodules.

PMID- 8761398
TI  - Case report: giant aneurysm of the intrapetrous carotid artery presenting as a
      cerebellopontine angle mass.

PMID- 8761399
TI  - Case report: upper extremity ischaemia secondary to ergotamine poisoning.

PMID- 8761400
TI  - Case report: percutaneous biopsy of a right atrial angiosarcoma under ultrasound
      guidance.

PMID- 8761401
TI  - Case report: migration and shortening of a self-expanding metallic stent
      complicating the treatment of malignant superior vena cava stenosis.

PMID- 8761402
TI  - Case report: Klippel-Trenaunay syndrome as a cause of erectile dysfunction.

PMID- 8761403
TI  - Unusual perirenal sonographic pattern in malignant lymphoma of the kidney.

PMID- 8761404
TI  - True massive thymic hyperplasia.

PMID- 8761405
TI  - Radial artery approach for outpatient peripheral arteriography.

PMID- 8761406
TI  - Femo-Stop II System Femoral Compression Arch.

PMID- 8761407
TI  - Relationship between the intracellular reactive oxygen species and the induction
      of oxidative DNA damage in human neutrophil-like cells.
AB  - To clarify the mechanisms of intracellular induction of oxidative DNA damage, we
      have investigated the concentrations of intracellular reactive oxygen species and
      the amounts of 8-hydroxydeoxyguanosine (8OHdG), a mutagenic oxidative DNA damage,
      in human neutrophil-like cells, dimethylsulfoxide-differentiated HL60 (DMSO
      HL60). We determined intracellular concentrations of hydrogen peroxide and
      superoxide by flow cytometry with dichlorofluorescein diacetate and
      hydroethidine, respectively. We determined the 8OHdG amounts with an
      electrochemical detector connected to HPLC after anaerobic sample processing.
      DMSO-HL60 releases superoxide upon stimulation with phorbol myristate acetate,
      and the released superoxide dismutates to hydrogen peroxide. Stimulation of DMSO
      HL60 with 100 nM phorbol myristate acetate increased intracellular hydrogen
      peroxide, superoxide and 8OHdG (control). Addition of 1000 U/ml catalase
      decreased hydrogen peroxide (31.3% of control) and 8OHdG (20.3%). Addition of 100
      U/ml SOD decreased superoxide (18.7%) and 8OHdG (41.6%). Addition of 1 mM
      deferoxamine decreased 8OHdG (30.4%), but increased hydrogen peroxide (129.6%).
      Addition of 200 microM 4-acetamido-4'- isothiocyanostilbene-2,2'-disulfonic acid
      decreased superoxide (59.9%) and 8OHdG (42.0%). Addition of 0.4% ethanol had no
      effect on superoxide concentration (102.2%), but tended to decrease hydrogen
      peroxide (83.5%) and 8OHdG (84.3%). Pretreatment of DMSO-HL60 with 0.1 mM FeSO4
      increased 8OHdG (117.3%), but decreased hydrogen peroxide (75.8%). These findings
      indicate that the extracellularly released superoxide and hydrogen peroxide
      diffuse into the cell, but that such reactive oxygen species are not the direct
      molecules to induce 8OHdG. Our results suggest that 8OHdG is induced by the
      hydroxyl radical which is generated from intracellular hydrogen peroxide and
      superoxide-reduced Fe.

PMID- 8761408
TI  - Nucleotide level detection of cyclobutane pyrimidine dimers using
      oligonucleotides and magnetic beads to facilitate labelling of DNA fragments
      incised at the dimers and chemical sequencing reference ladders.
AB  - We present a method for detecting cyclobutane pyrimidine dimers (CPDs) at the
      nucleotide level and an adaptation of Maxam-Gilbert sequencing for generating
      sequence reference ladders. UV irradiated genomic DNA from Escherichia coli was
      digested with restriction enzyme(s) and incised at the CPDs with Micrococcus
      luteus UV endonuclease. The subsequent specific fragments were separated using a
      biotin labelled oligonucleotide containing a sequence complementary to the
      fragments of interest and streptavidin magnetic beads. These fragments were then
      radiolabelled on the beads just prior to the running of the sequencing gel. For
      generating sequence reference ladders, the unlabelled DNA fragments of interest
      were base-specifically modified and subsequently cleaved at the A+G or C+T sites
      using the rapid Maxam-Gilbert sequencing treatments. These chemically cleaved
      fragments can be stored almost indefinitely. Whenever the sequence reference
      ladders are required, the chemically cleaved fragments can be labelled alongside
      the CPD-specifically incised DNA fragments using the same procedure. The
      adaptation of the method to detect other types of DNA damage is also discussed.

PMID- 8761409
TI  - Formation and accumulation of DNA ethenobases in adult Sprague-Dawley rats
      exposed to vinyl chloride.
AB  - DNA ethenobases are promutagenic lesions formed by carcinogens such as vinyl
      chloride (VC). Their formation was investigated in 6-week old, male Sprague
      Dawley rats exposed to 500 p.p.m. VC by inhalation (4 h/day, 5 days/ week) for 1,
      2, 4 or 8 weeks and in 7- and 14-week old, matched control animals. 1,N6
      Ethenoadenine (epsilon A) and 3, N4-ethenocytosine (epsilon C)
      deoxyribonucleotides were analysed by immunoaffinity purification and 32P
      postlabelling. This postlabelling method was compared with a radio-immunoassay
      method, which yielded similar results. Background levels of ethenobases were
      found in DNA from the liver, lungs, kidneys and circulating lymphocytes of
      unexposed, control rats. In the liver, the following background molar ratios of
      ethenobase to parent base in DNA were detected (mean values x 10(-8)): epsilon
      A/A, 0.04-0.05; epsilon C/C, 0.06-0.07. In the lungs, kidneys and circulating
      lymphocytes, background levels of epsilon A and epsilon C ranged from 1.7 to 4.2
      x 10(-8) and from 4.8 to 11.2 x 10(-8), respectively. Following a 5-day exposure
      to VC, a significant increase of epsilon A and epsilon C was measured in hepatic
      DNA from rats sacrificed immediately after treatment. Further, a dose-dependent
      increase of both etheno adducts was observed in liver DNA of VC-treated rats.
      Compared to the 5-day exposure, approximately 4-fold higher levels of epsilon A
      and epsilon C were observed in the liver of animals after 8 weeks of exposure. In
      contrast, there was an accumulation of epsilon C but not of epsilon A in lungs
      and kidneys. In circulating lymphocytes, no significant increase of ethenobase
      levels above control values was observed after 2 months of exposure to VC. Both
      etheno adducts were found to be persistent in liver DNA, after 2 months following
      the termination of VC exposure. These results further support the notion that DNA
      etheno-bases are critical lesions in VC-induced carcinogenesis. The possible
      contribution of lipid peroxidation products that also yield ethenobases, on the
      formation and persistence of these DNA adducts, remains to be clarified.

PMID- 8761410
TI  - Cloning, genetic mapping and expression studies of the rat Brca1 gene.
AB  - The breast cancer gene BRCA1 has previously been cloned from both human and
      mouse. We cloned a fragment of the rat Brca1 homologue in order to map it and
      explore its biological function. Partial cDNA fragments of the rat Brca1
      homologue were isolated by RT-PCR. Sequence analysis revealed that the RING
      finger domain is well conserved among rat, mouse and human. Rat Brca1 mRNA was
      expressed in most tissues studied with the highest level in testis, consistent
      with studies in human and mouse. Next, intron 6-containing DNA fragments were
      amplified by PCR from WKY and WF rat strains. The splicing sites between exon 6
      and exon 7 are conserved between rat and human. Partial sequencing of the rat
      Brca1 intron 6 revealed a polymorphism of a pentanucleotide TTTTG repeat between
      the WKY and WF strains. With this intragenic microsatellite marker, we were able
      to map precisely the rat Brca1 gene to chromosome 10 using a genetic linkage
      study of (WKY x WF)F1 x WF backcross rats. Brca1 cosegregates with marker BAND3A,
      and is flanked by R5123 and R5842. Using this polymorphic marker, we also
      investigated the loss of heterozygosity (LOH) of the Brca1 microsatellite marker
      in carcinogen- or radiation-induced mammary carcinomas in (WF x F344)F1 female
      rats. No LOH or somatic microsatellite instability was detected in 18 DMBA
      induced tumors studied. Only one LOH of the F344 allele was observed in 26
      radiation-induced tumors tested. Ribonuclease protection assays demonstrated that
      Brca1 mRNA levels are similar in normal rat mammary glands and mammary carcinomas
      of various etiologies, including those induced by DMBA, NMU, activated-neu and
      activated-ras oncogenes.

PMID- 8761411
TI  - Identification of human tumour suppressor genes by monochromosome transfer: rapid
      growth-arrest response mapped to 9p21 is mediated solely by the cyclin-D
      dependent kinase inhibitor gene, CDKN2A (p16INK4A).
AB  - Microcell transfer of intact normal human chromosomes into immortal mouse and
      hamster fibroblast cell lines has revealed growth suppressive activity associated
      with a small sub-set of the human complement. Here, we describe the results of a
      detailed study aimed at identifying the gene or genes responsible for the rapid
      growth-arrest response obtained with human chromosome-9. Initially, STS-PCR
      deletion mapping of segregants arising in monochromosome transfer experiments was
      used successfully to localize the active sub-chromosomal region to 9p21.
      Subsequent fine-structure deletion mapping of previously uniformative hybrid
      segregants, employing additional markers between D9S162 and D9S171, provided
      strong evidence that the cyclin-dependent kinase (cdk) inhibitor gene CDKN2A
      (p16INK4A) was solely responsible for the chromosome-9 effect; 9p21
      microdeletions in a significant proportion of segregant clones were restricted to
      a single CDKN2A exon. Transfection experiments with CDKN2A and CDKN2B cDNA
      expression vectors, using mouse A9 cells and three human malignant melanoma cell
      lines as recipients, provided further evidence in support of this hypothesis.
      Collectively, our results indicate that expression of human CDKN2A (controlled
      either by its natural regulatory elements, or by a cytomegalovirus promoter) is
      incompatible with in vitro proliferation in immortalized rodent cells and in
      human melanoma cell lines. The rapidity of the growth inhibitory effects of
      CDKN2A was inconsistent with a mode of action involving induction of replicative
      cell senescence via telomerase repression, but was consistent with a mechanism
      based on cell cycle arrest through cdk inhibition. The study described here has
      generated a panel of microdeleted monochromosome-9 donor hybrids which may prove
      valuable in functional investigations aimed at identifying other important tumour
      suppressor genes located on human chromosome-9.

PMID- 8761412
TI  - Tamoxifen associated uterine pathology in rodents: relevance to women.
AB  - Rats administered tamoxifen for 3 months and then returned to a basal diet
      developed an increase in uterine weight for up to 9 months after tamoxifen
      exposure. Stereological analysis of the tamoxifen exposed rat uteri showed that
      there was a significant increase in the amount of uterine myometrium, for a
      further 9 months, subsequent to the discontinuation of tamoxifen. A low incidence
      of myometrial proliferations (deciduomas) and uterine tumours was found at the
      conclusion of the study (20 months). In contrast, continuous administration of
      tamoxifen to mice for 24 months produced hyperplasia of the uterine endometrial
      epithelium and atrophy of the myometrium for the first 3 months, followed by
      atrophy of both the endometrium and myometrium for the remaining 21 months of the
      study. No uterine tumours were found in mice treated with tamoxifen for 2 years.
      The use of stereological analysis on interim sacrifice rodent uteri indicated
      that sustained uterine tissue compartment effects can occur, with either the
      continuous administration of tamoxifen, or after its discontinuation. Tamoxifen
      can have an agonist and antagonist like effect on oestrogen activity in different
      tissue compartments of the mouse uterus, over the same time period. The
      particular relevance of the finding of uterine proliferation and atrophy in the
      rodent studies with tamoxifen is discussed with regard to women taking this drug.

PMID- 8761413
TI  - Overexpression of cyclin D1 and cyclin E in N-nitrosomethylbenzylamine-induced
      rat esophageal tumorigenesis.
AB  - Dysregulation of G1 cyclins has been implicated in several human malignancies. To
      further investigate the role of G1 cyclins in chemical carcinogenesis, the
      expression of cyclin D1 and cyclin E was analyzed by RT-PCR and
      immunohistochemical studies in N-nitrosomethylbenzylamine (NMBA)-induced rat
      esophageal tumorigenesis. Cyclin D1 mRNA levels were increased 2.8-fold in 25
      week (P < 0.05) and 6.8-fold in 45 week (P < 0.01) papillomas induced by NMBA,
      when compared with normal rat esophageal epithelium. Cyclin E mRNA levels were
      increased 6.2-fold in 25 week (P < 0.01) and 6.9-fold in 45 week (P < 0.01)
      papillomas. Immunohistochemical staining revealed exclusive nuclear staining of
      both cyclin D1 and cyclin E. Furthermore, there was a sequential increase in
      cyclin D1- and cyclin E-positive cells from normal epithelium, to preneoplastic
      lesions, to papillomas. These findings suggest that overexpression of cyclin D1
      and cyclin E occur relatively early in rat esophageal tumorigenesis and
      participate in tumor progression in this model.

PMID- 8761414
TI  - 2q-, a non-random chromosomal abnormality in human non-small-cell lung cancer.
AB  - Many cytogenetic studies have been carried out on human lung cancer. However the
      chromosomal alterations in human lung cancers are often complex, making it
      difficult to identify some abnormal chromosomes by routine cytogenetic studies.
      Using FISH (fluorescence in situ hybridization), we studied the alterations of
      chromosome 2, 3, and 17 in four human bronchial epithelial cell lines, two human
      non-small-cell lung cancer (NSCLC) cell lines, and 12 primary NSCLC specimens. 2q
      was found in three out of four human bronchial epithelial cell lines, two NSCLC
      cell lines, and three out of seven primary NSCLC specimens tested. 3p- was noted
      in five cases of twelve primary NSCLC patients examined. 3p- was the first
      cytogenetic discovery and the most prominent abnormality in lung cancer. 2q- has
      rarely been reported in human lung cancer but loss of heterozygosity by RFLP
      analysis for 2q had been reported in human NSCLC. Our results indicate that 2q-
      was also a non-random chromosomal abnormality in the early stage of the
      development of human NSCLC. There would be one or more putative tumor suppressor
      gene(s) on the long arm of chromosome 2. Loss of the gene(s) presumably
      contributes to the carcinogenesis of human non-small-cell lung cancer.

PMID- 8761416
TI  - Contribution of ogt-encoded alkyltransferase to resistance to
      chloroethylnitrosoureas in nucleotide excision repair-deficient Escherichia coli.
AB  - We investigated the relative contribution of the two Escherichia coli DNA
      alkyltransferases (ATases) to the increased sensitivity of ATase-deficient
      bacteria to the mutagenic and lethal effects of chloroethylnitrosoureas (CNU).
      The ogtencoded protein was the principal determinant in resistance to the
      mutagenic effects of CNU in E.coli. Thus, only when the ogt gene was inactivated
      was sensitivity to mutagenesis greatly increased; the contribution of
      inactivation of the ada gene was relatively minor. Furthermore, induction of the
      adaptive response provided essentially no protection against CNU mutagenesis in
      either an ogt+ or ogt- background. Finally, overexpression of the ogt gene into
      ogt- ada- double mutants provided the greatest protection against CNU;
      introduction of the full-length or truncated ada gene was protective, but to a
      much lesser extent. Mammalian ATases were not as protective against mutation
      induction by CNU as Ogt, even though they were apparently expressed at higher
      level. In order of effectiveness the ATases ranked Ogt > human > truncated Ada =
      Ada > rat. This order was not observed in the protection against killing by 1-(2
      chloroethyl)-3-cyclohexyl-1-nitrosourea, where truncated Ada = human > Ogt > rat
      = Ada. Higher mutation frequency and toxicity were observed in uvr- mutants,
      suggesting that one or more of the potentially mutagenic and/or toxic lesions are
      also substrates for the excision repair proteins.

PMID- 8761415
TI  - Active cell death induced by the anti-estrogens tamoxifen and ICI 164 384 in
      human mammary carcinoma cells (MCF-7) in culture: the role of autophagy.
AB  - Active cell death in hormone-dependent cells was studied using cultured human
      mammary carcinoma cells (MCF-7) treated with the anti-estrogens (AEs) tamoxifen
      (TAM), 4-hydroxy-tamoxifen (OH-TAM) or ICI 164 384 (10(-8)-10(-5) M) as a model.
      The following results were obtained. (i) In untreated MCF-7 cells a wave of
      replication occurred in the first 5 days of culture. All three AEs caused a dose
      dependent inhibition of cell replication. (ii) TAM and OH-TAM at 10(-5) M, but
      not ICI 164 384, caused lytic cell death (necrosis) within 24 h, which was not
      inhibited by estradiol (10(-9)-10(-6)M). (iii) Lower concentrations of TAM or OH
      TAM (up to 10(-6) M) or ICI 164 384 induced a more gradual appearance of cell
      death beginning at day 3. This type of cell death was inhibited by estradiol (10(
      9) M), indicating its active nature. (iv) Nuclei showed two distinct patterns of
      alteration: (a) apoptosis-like condensation and fragmentation of chromatin to
      crescent masses abutting the nuclear envelope; (b) condensation of the chromatin
      to a single, pyknotic mass in the center of the nucleus, detached from the
      nuclear envelope. Quantitative histological evaluation revealed the predominance
      of pyknosis. (v) Biochemical DNA analysis revealed that only a relatively small
      amount of the total DNA was finally degraded into low molecular weight fragments
      (20 kb and less). (vi) Active cell death, with both apoptotic and pyknotic
      nuclear morphology, was associated with extensive formation of autophagic
      vacuoles (AV).3-Methyladenine, a known inhibitor of AV formation, partially
      prevented cell death as detected by nuclear changes. (vii) ICI 164 384 was about
      10 times more effective than TAM or OH-TAM at inhibiting DNA synthesis, but had
      equal potency in inducing active cell death. It is concluded that AEs have anti
      proliferative and anti-survival effects on MCF-7 human mammary cancer cells in
      culture. These two effects are under separate control because they differ by
      kinetics, dose dependence and sensitivity to the various AEs. Active cell death
      in MCF-7 cells seems to be initiated by autophagy, in contrast to concepts of
      apoptosis, and thus corresponds to autophagic/ lysosomal or type II death as
      previously defined. This may be important because of biochemical and molecular
      differences between these various subtypes of active cell death.

PMID- 8761417
TI  - Involvement of transforming growth factor-alpha and its receptor in a model of
      DES-induced renal carcinogenesis in the Syrian hamster.
AB  - This study explores the role played by TGF alpha in estrogen-induced renal
      tumors. Tumors were induced in male Syrian hamster by chronic administration of
      diethylstilbestrol (DES). Six experimental groups (n = 5-9) were chronically
      exposed to DES and sacrificed after 1, 2, 4, 6, 9 and 11 months, respectively. In
      the course of treatment, the nephrons were the site of an important increase of
      cell turnover, which was characterized by a process of hyperplasia/dysplasia in
      proximal tubules preceding the neoplastic transformation. In treated animals and
      in controls, the analysis of renal tissue by Western blot revealed the presence
      of a 6 kDa polypeptide crossreacting with anti-TGF alpha antibody. In controls,
      TGF alpha immunoreactivity was localized in proximal and in distal tubules.
      Before tumor development (1-4 months), TGF alpha RIA showed an increase of TGF
      alpha concentration in renal tissue, in parallel with the increased cell
      proliferation observed in proximal tubules. In addition, Western blot analysis
      also demonstrated in kidney tissue the presence of a 165 kDa protein displaying
      the immunoreactivity of EGF/TGF alpha receptor. The receptor immunoreactivity was
      localized in proximal tubular cells suggesting an involvement of TGF alpha in
      tubular epithelial growth through autocrine or paracrine pathways. In large
      neoplasms, immunocytochemistry revealed only clusters of transformed cells
      intensely stained by the anti-TGF alpha antibody. These cells displayed the
      appearance of stellate or polyhedric cells infiltrating adjacent neoplastic
      tissues. Antisera raised against intra- or extracytoplasmic domains of the
      EGF/TGF alpha receptor were assayed to localize this receptor in the tumors. In
      contrast with tubular structures, immunoreactivity to EGF/TGF alpha receptor was
      never detected in tumoral tissue. The apparent absence of EGF/ TGF alpha receptor
      immunoreactivity in malignant cells seems to exclude an involvement of this
      growth factor in the tumorigenic process, although it could be involved in tumor
      neovascularization.

PMID- 8761418
TI  - Species differences in response to peroxisome proliferators correlate in vitro
      with induction of DNA synthesis rather than suppression of apoptosis.
AB  - Tumorigenesis caused by the peroxisome proliferator (PP) class of non-genotoxic
      hepatocarcinogens is species restricted; rat and mouse are considered responsive
      whereas the available evidence suggests that humans, non-human primates, dogs,
      hamsters and guinea pigs are non-responsive. We have demonstrated previously that
      the PP, nafenopin can suppress rat hepatocyte apoptosis both in vitro and in
      vivo. Here we describe the ability of nafenopin to suppress apoptosis in mouse,
      hamster, guinea pig and rat hepatocytes and induce S-phase in mouse and rat
      hepatocytes. Hepatocyte monolayers from all species examined degenerated rapidly
      in culture. However, nafenopin (50 microM) reversibly maintained the viability of
      both rat and mouse hepatocytes. This maintenance was associated with a decrease
      (P < or = 0.01) in the number of hepatocytes displaying chromatin condensation
      patterns characteristic of apoptosis. Treatment of rat and mouse monolayers with
      5 ng/ml transforming growth factor-beta 1 (TGF beta 1) induced high levels of
      apoptosis (P < or = 0.01); co-addition of nafenopin suppressed this induced
      apoptosis (P < or = 0.01). TGF beta 1 also induced apoptosis in hamster and
      guinea pig hepatocytes (P < or = 0.01) and unexpectedly nafenopin was able to
      suppress this induced apoptosis (P < or = 0.01) as well as reversibly maintaining
      the viability of hamster and guinea pig hepatocyte monolayers. Thus, all the
      species examined responded to nafenopin by a suppression of both spontaneous and
      TGF beta 1-induced apoptosis. In contrast, only rat and mouse hepatocytes showed
      an induction of S-phase in response to nafenopin (P < or = 0.01). Certain key
      experiments were repeated using the PPs methyl clofenapate (MCP) (100 microM) and
      Wy-14, 643 (10 microM). Both were able to suppress spontaneous and TGF beta 1
      induced apoptosis in rat and guinea pig hepatocytes although the effects of MCP
      were weak (P < or = 0.05) compared with nafenopin or Wy-14 643 (P < or = 0.01).
      The rat and mouse liver tumour promoter, phenobarbitone (PB) was assessed also.
      Rat hepatocytes responded to PB with a suppression of apoptosis and an induction
      of S-phase (P < or = 0.01). Hamster and guinea pig cells gave no response in the
      S-phase assay and exhibited no suppression of either spontaneous or TGF beta 1
      induced apoptosis. Interestingly, nafenopin suppressed the apoptosis induced by
      the DNA damaging drugs, etoposide and hydroxyurea (P < or = 0.01) suggesting that
      PPs can impact on diverse apoptosis signalling pathways. Overall, species
      differences in response to the non-genotoxic hepatocarcinogens studied, correlate
      with induction of DNA synthesis rather than with suppression of apoptosis. The
      data extend our knowledge of the mechanisms of species differences in non
      genotoxic hepatocarcinogenesis, posing interesting questions on the relative
      roles of apoptosis and DNA synthesis in carcinogenesis.

PMID- 8761419
TI  - Radiation-induced genomic instability and persisting oxidative stress in primary
      bone marrow cultures.
AB  - There is accumulating evidence that cells exposed to low and often
      environmentally relevant doses of ionizing radiation survive the initial insult,
      but transmit genomic instability to their progeny. The underlying mechanism of
      radiation-induced genomic instability is unknown. We present bio-chemical
      evidence consistent with the hypothesis that enhanced and persistent oxy-radical
      activity may be responsible.

PMID- 8761420
TI  - Prostate specific antigen and androgen receptor induction and characterization of
      an immortalized adult human prostatic epithelial cell line.
AB  - Progress in prostate cancer research has been hindered by the lack of well
      characterized, immortalized, human prostatic epithelial cell lines that express
      markers of normal prostatic epithelial cells and mimic normal growth and
      differentiation responses to androgens. The objectives of this study were to: (i)
      establish immortalized cell lines from non-neoplastic, adult human prostatic
      epithelium using adenovirus-12/simian virus-40 (Ad12-SV40) hybrid virus; (ii)
      establish their prostatic epithelial origin; (iii) demonstrate androgen
      responsiveness; and (iv) examine response to growth factors. Primary epithelial
      cell cultures derived from a non-neoplastic, adult human prostate were infected
      with the Ad12-SV40 virus. Several immortalized clones were isolated. Single cell
      cloning of one clone, free of cytopathic effects, gave rise to the PWr-1E cell
      line. An immortalized cell line PWR-1E, which expresses many characteristics of
      normal prostatic epithelial cells was established. Immunostaining showed that
      cells express cytokeratins 8 and 18 normally expressed by differentiated,
      secretory prostatic epithelial cells. The most remarkable characteristics of PWR
      1E cells are growth stimulation, increased expression of androgen receptor and
      induction of prostate specific antigen (PSA) expression in response to androgens,
      which indisputably establish their prostatic epithelial origin. They are positive
      for SV40 large-T antigen and show strong nuclear staining for p53. Cells from
      passages 23 and 40 were not tumorigenic in nude mice even when co-injected with
      Matrigel. They grow in a serum-free defined medium and respond to EGF, bFGF and
      TGF-beta. Passage 42-cells showed a human male (XY), hyperdiploid karyotype. The
      PWR-1E cell line is the only known Ad12-SV40-immortalized human prostatic
      epithelial cell line. PWR-1E cells can be used to study (i) the etiology and the
      multistep process of carcinogenesis and tumor progression in the human prostate;
      (ii) normal prostate physiology and differentiation; and (iii) potential prostate
      cancer chemopreventive agents.

PMID- 8761421
TI  - Hepatocyte expression of tumor associated aldehyde dehydrogenase (ALDH-3) and p21
      Ras following diethylnitrosamine (DEN) initiation and chronic exposure to di(2
      ethylhexyl)phthalate (DHEP).
AB  - Phthalate esters such as di(2-ethylhexyl)phthalate (DEHP) either promote or
      inhibit rat liver tumorigenesis depending on the carcinogenesis protocol. In this
      study, we examined the expression of two histochemical markers, the tumor
      associated isozyme of aldehyde dehydrogenase (ALDH-3) and the oncoprotein p21
      Ras, in the livers of male F344 rats. The rats were initiated with DEN and
      further treated with either DEHP (a known inhibitor of hepatocarcinogenesis),
      phenobarbital (PB, a known promoter of hepatocarcinogenesis), or a combination of
      DEHP and PB. The studies were designed to examine the expression of these markers
      in both normal appearing liver and hepatic hyperplastic and neoplastic lesions
      and to correlate the early expression of the markers at 26 weeks in the normal
      appearing liver to later tumor incidence at 52 weeks. The expression of each
      marker was detected by immunohistochemical methods on formalin-fixed paraffin
      embedded sections of normal appearing liver or liver lesions. We found that ALDH
      3 and p21 expression were significantly enhanced in rats receiving PB after DEN
      initiation at 26 weeks and that the incidence of hepatocellular carcinomas was
      likewise increased compared to control or DEN only treated animals. DEN
      initiation followed by a combination of PB and either 0.1 or 0.5% DEHP
      significantly reduced ALDH-3 but not p21 Ras expression at 26 weeks compared to
      DEN plus PB only. These treatment regimens also reduced the incidence of
      hepatocellular carcinomas at 52 weeks. DEN followed by any of the three doses of
      DEHP without PB resulted in ALDH-3 expression similar to DEN alone. However, p21
      Ras expression was significantly increased after these treatments. For all
      treatment groups, both the early (26 weeks) expression of p21 Ras and ALDH-3
      correlated with hepatocellular carcinoma incidence at 52 weeks. However, the
      correlation between hepatocellular carcinoma and ALDH-3 expression was better
      than p21 Ras or the other markers we have studied. We concluded that ALDH-3
      expression is significantly downregulated after DEHP treatment, and that
      expression of the isozyme correlated with later hepatocarcinoma incidence and may
      indicate a significant relationship between ALDH-3 expression and
      hepatocarcinogenesis during DEHP treatment.

PMID- 8761422
TI  - Inhibition of tumor promotion and hepatocellular growth by dietary restriction in
      mice.
AB  - The effects of dietary restriction on the growth of hepatic focal lesions in
      phenobarbital (PB) promoted mice were examined. Dietary restriction which can
      inhibit many age-related diseases in rodents including hepatic cancer also
      decreases cell proliferation and increases apoptosis in the liver. In contrast,
      PB, a non-genotoxic rodent hepatocarcinogen, enhances the growth of hepatic focal
      lesions in mice and rats by increasing cell proliferation and inhibiting
      apoptosis. The present study examined the impact of dietary restriction on PB
      induced hepatic tumor promotion. Focal lesions were produced by
      diethylnitrosamine (DEN) treatment (35 mg DEN/kg body weight injections, twice
      per week for 8 weeks). After lesions were produced, mice were placed into one of
      the following four groups: NIH-07 control diet/no PB (group 1); NIH-07 diet/500
      mg PB per liter of drinking water (group 2); dietary restricted NIH-07 diet/no PB
      (group 3); and dietary restricted NIH-7 diet/ 500 mg PB per liter of drinking
      water (group 4). In this study, PB (500 mg/l) treatment to ad libitum-fed mice
      (group 2) enhanced focal lesion volume, number, and labeling index compared with
      group 1. In addition, PB treatment (group 2) inhibited apoptosis in normal and
      focal hepatocytes compared with untreated control mice (group 1). In contrast, in
      dietary restricted mice treated with PB (group 4) a significantly lower focal
      lesion volume, number and labeling index were seen compared with the ad libitum
      fed/PB treatment group (group 2). PB treatment in dietary restricted mice (group
      4) did not inhibit focal apoptosis, in fact, the incidence of focal apoptosis was
      increased in these mice compared with ad libitum and PB-treated mice (group 2).
      In dietary restricted mice treated with PB (group 4), the ability of PB to
      promote the growth of preneoplastic focal lesions was inhibited. These results
      show that dietary restriction can ablate the tumor promotional effects of PB in
      hepatic focal lesions and suggest that inhibition of focal lesion DNA synthesis
      and enhancement of apoptosis may be a mechanism for this effect.

PMID- 8761423
TI  - Cisplatin-DNA adduct formation in maternal and fetal rat tissues after
      transplacental cisplatin exposure.
AB  - Cis-diamminedichloroplatinum (II) (cisplatin), given to pregnant rats at 5 mg/kg
      body weight (bw) is a trans placental carcinogen for fetal liver, kidney, nervous
      system and lung, resulting in tumor incidences of 22.5, 10.5, 6.1 and 7.5%
      respectively, in offspring grown to adulthood (B.A. Diwan et al., 1995, Toxicol.
      Appl. Pharm., 132, 115). In this study, the capacity of cisplatin to pass through
      the placental barrier and bind covalently to DNA in maternal and fetal tissues
      was evaluated. Pregnant F344/NCr rats were injected i.p. with single doses of 5,
      10 or 15 mg cisplatin/kg bw at 18 days of gestation and sacrificed 24 h later.
      Cisplatin-DNA adducts were determined by dissociation-enhanced lanthanide
      fluoroimmunoassay (DELFIA) using both High (90 pmol/micrograms DNA) and Low (0.50
      pmol/ microgram DNA) Modified cisplatin-DNA standards and atomic absorbance
      spectrometry (AAS). The adduct quantities determined by the two DELFIAs varied in
      concert, but the DELFIA with Low Modified standard gave actual values similar to
      those observed with AAS. In maternal and fetal tissues, with the exception of
      placenta in one experiment and maternal kidney in another experiment, the extent
      of cisplatin-DNA adduct formation increased with dose. In maternal kidney, the
      low adduct levels observed at the 15 mg/kg dose may reflect kidney toxicity.
      Fetal kidney, liver and lung contained fewer cisplatin-DNA adducts than the
      corresponding maternal tissues. In contrast, at 5 and 15 mg/kg, fetal brain DNA
      contained higher adduct levels than maternal brain DNA. This study demonstrates
      the presence of DNA damage induced by cisplatin in multiple maternal and fetal
      rat tissues at tumorigenic doses of drug; the results are therefore consistent
      with the hypothesis that genotoxic mechanisms play an important role in the drug
      induced tumor incidence.

PMID- 8761424
TI  - Induction of genomic instability in normal human bronchial epithelial cells by
      238Pu alpha-particles.
AB  - Pulmonary deposition of alpha-particle-emitting radon daughters is estimated to
      account for 10% of all lung cancer deaths in the USA. However, the nature and
      timing of early (preneoplastic) genetic alterations in radon-associated lung
      cancer are still relatively uncertain. The purpose of this investigation was to
      determine whether genomic instability occurs after exposure of cultured normal
      human bronchial epithelial cells to six equal, fractionated doses of alpha
      particles (total doses 2-4 Gy). Two weeks after the final exposure, foci of
      phenotypically altered cells (PACs) were detected in 0, 63 and 77% of control,
      low and high dose cultures respectively. Of these, 18% exhibited extended life
      spans relative to unexposed controls. Elevated frequencies of binucleated cells
      (BNCs), a marker of genomic instability, were observed in 60 and 38% of the PAC
      cultures from the low and high dose groups respectively. The micronucleus assay
      also showed evidence of genomic instability in 40 and 38% of PAC cultures from
      the low dose and high dose groups respectively. No changes in microsatellite
      length, another marker of genomic instability, were detected in any of the PAC
      samples with the 28 markers used for this assay. However, one PAC (L2) showed a
      hemizygous deletion at 9p13.3. Another PAC (H9), which exhibited the highest
      frequency of cells containing micronuclei (MN), exhibited a hemizygous deletion
      at 7q31.3. Each loss may represent a stable mutation that resulted either
      directly from irradiation or later in progeny of exposed cells because of alpha
      particle-induced genomic instability. The fact that elevated levels of BNCs and
      MN were present in the progeny many generations after irradiation indicates that
      the genetic alterations detected with these two markers were not a direct
      consequence of radiation exposure, but of resulting genomic instability, which
      may be an early change after exposure to alpha-particles.

PMID- 8761425
TI  - GSTM1 and NAT2 genotypes and urinary mutagens in coke oven workers.
AB  - The influence of the metabolic genotypes GSTM1 and NAT2 on the urinary excretion
      of mutagens in 46 coke oven workers (27 of them smokers) was studied. Exposure to
      polycyclic aromatic hydrocarbons (PAH) was estimated from urinary 1-pyrenol
      levels, which varied from 0.23 to 5.59 micromol/mol creatinine. Fourteen urine
      samples (30.4%), all but one belonging to smokers, were positive for mutagenic
      activity (i.e. at least one of the assayed doses was able to double the number of
      spontaneous revertants). Nine of the urine-positive subjects were both GSTM1-null
      and NAT2-ss (64.3%), while the same combination of genotypes was found in nine
      out of 31 urine-negative subjects (29.0%) (P < 0.05). Significantly more smoking
      workers with the genotype combination GSTM1-null/NAT2-ss showed positive urine
      mutagenicity than the other subjects (75.0 versus 28.6%, P < 0.05). Smokers with
      the slow acetylator genotype showed a significantly higher frequency of positive
      urine samples than smoking fast acetylators (64.7 versus 22.2%, P < 0.05). Our
      results suggest that smoking coke oven workers with genotypes unfavourable for
      detoxification of aromatic amines (NAT2-ss) and PAH (GSTM1-null) may have an
      increased risk of developing bladder cancer.

PMID- 8761426
TI  - K-ras gene mutation in sputum samples containing atypical cells and
      adenocarcinoma cells in the lung.
AB  - We analyzed the presence or absence of K-ras mutations in sputum samples with
      atypical cells by colony hybridization. The frequency of K-ras mutations in 104
      patients with adenocarcinoma of the lung was also examined using dot blotting. No
      mutations in K-ras codon 12 were detected in the 12 sputum samples examined,
      which included three specimens from patients who later developed lung
      adenocarcinoma. Because of the paucity of sputum samples, it was difficult to
      conclude whether K-ras gene mutations are useful for molecular screening for lung
      cancer at the present time. Secondly, we detected 12 cases [12%; 10 males (19%)
      and two females (4%)] with a K-ras mutation among 104 patients with lung
      adenocarcinoma. Although the smoking rate of patients (89%) was higher than the
      general Japanese male population (approximately 60%), indicating that smoking may
      be related to the occurrence of adenocarcinoma of the lung, it was unclear
      whether smoking was related to K-ras mutation from our results. Other factors may
      contribute to K-ras mutation.

PMID- 8761427
TI  - Effect of tamoxifen feeding on metabolic activation of tamoxifen by the liver of
      the rhesus monkey: does liver accumulation of inhibitory metabolites protect from
      tamoxifen-dependent genotoxicity and cancer?
AB  - Tamoxifen induces hepatocellular carcinomas in rats and is converted by rat
      hepatic cytochrome P450 enzymes into reactive metabolites capable of forming
      adducts with nucleic acids, proteins and chromosomal aberrations. In rats
      tamoxifen has also been shown to induce liver cytochrome P450 enzymes, to
      stimulate its own metabolism leading to greater covalent binding and to induce a
      higher degree of unscheduled DNA synthesis. This suggests that, at least in the
      rat, a sensitive species, tamoxifen may contribute significantly to its genotoxic
      and carcinogenic potential, by assisting its own metabolic activation. We have
      now investigated the effect of feeding tamoxifen to male and female Rhesus
      monkeys. A marked induction of the hepatic cytochrome(s) P450 is found in the
      monkey but, in spite of this, the in vitro metabolism of 7-ethoxyresorufin by
      microsomes from treated animals is markedly inhibited and so is the dealkylation
      of two other 7-alkoxyresorufin substrates. Evidence is presented for the
      accumulation in the liver of monkeys treated with tamoxifen of a powerful
      inhibitor of drug metabolism, and the inhibitor is identified as a metabolite of
      tamoxifen, its N,N-didesmethyl derivative. The level of 32P-postlabelled DNA
      adducts was considerably higher in rats given tamoxifen than in similarly treated
      monkeys. Also, whereas rats responded to tamoxifen treatment with a marked
      increase in covalent binding to microsomal protein, in the monkeys, where
      accumulation of the inhibitory metabolite in the microsomal fraction was also
      seen, covalent binding was not greater with microsomes from treated animals than
      in the corresponding controls. N,N-Didesmethyl-tamoxifen, added in vitro to human
      and rat microsomes, reduced significantly the extent of covalent binding,
      suggesting that the accumulation of the metabolite observed in the liver of
      primates may discourage the cytochrome P450-dependent conversion of tamoxifen
      into reactive derivatives and in this way protect against the formation of
      adducts. This mechanism may also contribute to protecting the primate against
      tamoxifen- induced liver cancer.

PMID- 8761428
TI  - Methotrexate alters carbon flow through the hepatic folate-dependent one-carbon
      pool in rats.
AB  - The chemotherapeutic value of methotrexate resides in its ability to perturb
      folate-dependent one-carbon metabolism and subsequently inhibit DNA synthesis. To
      assess the functional effect of methotrexate on hepatic one-carbon metabolism, we
      have developed and applied tracer kinetic techniques in vivo to quantify the
      carbon flux through the folate-dependent one-carbon pool in rats. Following a 7
      day treatment period with methotrexate (0.2 mg/kg body weight), the tracers L
      [ring-2-14C] histidine and L-[methyl-3H] methionine were simultaneously infused
      into control and methotrexate-treated rats. Methotrexate treatment decreased
      hepatic tetrahydrofolate, methyltetrahydrofolate, and formyltetrahydrofolate,
      concentrations by 63, 83, and 58%, respectively. Furthermore, the enzymatic
      activity of 10-formyltetrahydrofolate dehydrogenase, the terminal enzyme in the
      catabolism of the ring-2-carbon of histidine to CO2, was diminished by 32% in
      methotrexate-treated animals. These changes in enzyme activity and folate
      coenzyme concentrations did not result in a significant decrease in the oxidative
      flow of carbon from histidine to CO2 in methotrexate-treated rats compared to
      control animals (2.40 and 3.22 micromol/h/kg3/4, respectively). Oxidative carbon
      flow was reflective of tetrahydrofolate and formyltetrahydrofolate pools when
      expressed as a percent of total folate: neither coenzyme pool was diminished as a
      result of methotrexate treatment. In contrast, the reductive carbon flux through
      the one-carbon pool from histidine to methionine was significantly decreased 59%
      in methotrexate-treated (7.63 micromol/h/kg3/4) versus control rats (18.73
      micromol/h/kg3/4)). Likewise, methyltetrahydrofolate, as a percent of total
      folate, was reduced 51% in methotrexate-treated rats. Consequently, total
      measured carbon flow (oxidative+reductive) was 54% lower in rats subjected to
      subchronic methotrexate treatment. These tracer kinetic experiments
      quantitatively demonstrate the extent to which methotrexate alters the actual
      carbon flow through the hepatic folate-dependent one-carbon pool, primarily
      directed at diminishing the reductive carbon flow towards methyltetrahydrofolate
      and methionine synthesis.

PMID- 8761429
TI  - Benzo[b]fluoranthene: tumorigenicity in strain A/J mouse lungs, DNA adducts and
      mutations in the Ki-ras oncogene.
AB  - The polycyclic aromatic hydrocarbon benzo[b]fluoranthene (B[b]F) is a pervasive
      constituent of environmental combustion products. We sought to examine the lung
      tumorigenic activity of B[b]F in strain A/J mice, to study the relationship
      between formation and decay of B[b]F-DNA adducts and to examine mutations in the
      Ki-ras proto-oncogene in DNA from B[b]F-induced tumors. Mice were given i.p.
      injections of 0, 10, 50, 100 or 200 mg/kg body wt and lung adenomas were scored
      after 8 months. B[b]F induced significant numbers of mouse lung adenomas in a
      dose-related fashion, with the highest dose (200 mg/kg) yielding 6.95 adenomas/
      mouse, with 100% of the mice exhibiting an adenoma. In mice given tricaprylin,
      the vehicle control, there were 0.60 adenomas/mouse, with 55% of the mice
      exhibiting an adenoma. Based on dose, B[b]F was less active than benzo[a]pyrene.
      DNA adducts were analyzed qualitatively and quantitatively by 32P-post-labeling
      in lungs of strain A/J mice 1, 3, 5, 7, 14 and 21 days after i.p. injection.
      Maximal levels of adduction occurred 5 days after treatment with the 200 mg/kg
      dose group, producing 1230 amol B[b]F-DNA adducts/microgram DNA. The major B[b]F
      DNA adduct was identified by co-chromatography as trans-9, 10-dihydroxy-anti-11,
      12-epoxy-5-hydroxy-9, 10, 11, 12-tetra-hydro-B[b]F-deoxyguanosine. Approximately
      86% of the tumors had a mutation in codon 12 of the Ki-ras oncogene, as
      determined by direct DNA sequencing of PCR-amplified exon 1 and single-stranded
      conformation polymorphism analysis. Analysis of the Ki-ras mutation spectrum in
      25 of 29 B[b]F-induced tumors revealed the predominant mutation to be a G-->T
      transversion in the first or second base of codon 12, congruous with the DNA
      adduct data. Our data are consistent with previous reports in mouse skin
      implicating a phenolic diol epoxide as the proximate carcinogenic form of B[b]F
      that binds to guanine.

PMID- 8761430
TI  - Induction of humoral immunity toward 2-acetylaminofluorene in mice: modulation of
      DNA binding after 4 weeks dietary exposure to the carcinogen.
AB  - In order to investigate the modulatory effect of the immune response induced by
      recurrent carcinogen exposure, anti-2-acetylaminofluorene (anti-2-AAF) IgG were
      elicited in Swiss mice before subsequent carcinogen administration. The
      immunization schedule consisted of three weekly i.p. injections of 2
      acetylaminofluorene (2-AAF)-gelatin conjugate, followed by a final immunogen
      injection 14 days later. At the end of treatment, the presence of specific anti-2
      AAF antibodies in blood serum of all immunized animals was demonstrated. The
      immunization procedure did not affect liver metabolic activities, as evaluated
      using liver homogenates for the exogenous activation of 2-AAF to mutagen. After
      immunization, mice were fed 2-AAF pelleted in the diet at 50 and 150 p.p.m. for 4
      weeks and killed at the end of treatment. The determination of DNA adducts by
      ELISA in liver and spleen of treated animals revealed significantly (P < 0.01
      0.001) lower 2-AAF adduct levels in both tissues of immunized mice with respect
      to non-immunized animals (both naive and pretreated with the adjuvant alone).
      This result suggests that the specific humoral immunity elicited by repeated
      carcinogen exposure may be able to modulate the genotoxic effect induced by
      subsequent carcinogen administration.

PMID- 8761431
TI  - Detection of 1,N6-ethenodeoxyadenosine and 3,N4-ethenodeoxycytidine by
      immunoaffinity/32P-postlabelling in liver and lung DNA of mice treated with ethyl
      carbamate (urethane) or its metabolites.
AB  - The capacity of the chemical carcinogen ethyl carbamate (EC, urethane) and its
      metabolites vinyl carbamate (VC) and vinyl carbamate epoxide (VCO) to form
      ethenobases was studied in liver and lung DNA of 12-day-old and adult CD-1,
      B6C3F1, C3H/HeJ and C57BL/6J mice. Following single and multiple doses of EC, VC
      or VCO, the formation of 1,N6-ethenodeoxyadenosine (epsilon dA) and 3,N4
      ethenodeoxycytidine (epsilon dC) was quantified by an immunoaffinity
      chromatography/32P-postlabelling technique. Both etheno adducts were detected in
      untreated control DNA samples from liver and lung in the range of 2-15
      adducts/10(9) parent nucleotides. Following five repeated injections of 250 or
      280 nmol/g body wt VC to adult mice, 51, 57 and 78 epsilon dA/10(9) dA and 28, 42
      and 42 epsilon dC/10(9) dC (means of duplicate analyses) were detected in liver
      DNA of CD-1, C3H/HeJ and C57BL/6J mice respectively. In lung DNA of these VC
      treated mice, the levels were 87, 49 and 58 (epsilon dA/10(9) dA) and 64, 39 and
      43 (epsilon dC/10(9) dC) respectively. Under similar dose regimens, lower levels
      of etheno adducts were detected in B6C3F1 mice. Etheno-DNA adducts were also
      formed in liver and lung upon treatment with EC in adult mice, but at 3-fold
      lower levels as compared with VC. In 12-day-old C3H/HeJ and C57BL/6J mice, 2- to
      3-fold higher etheno adduct levels were detected in liver DNA, when compared with
      adults, upon a single treatment with 250 nmol/g body wt VC, suggesting that young
      animals are more susceptible to adduct formation. Combined analysis of adduct
      formation in adult CD-1, C3H/HeJ and C57BL/6J mice at the higher dose showed a
      statistically significant increase in etheno adduct formation in the order EC >
      VC. The results demonstrate that EC and its activated intermediates bind to liver
      and lung DNA to form epsilon dA and epsilon dC, and the differences in DNA
      binding further support the hypothesis that metabolic activation of EC to VC is
      involved. Preliminary data also suggest that background levels of epsilon dA and
      epsilon dC in DNA are affected by the type of diet given to the animals.

PMID- 8761432
TI  - Inhibition of pro-inflammatory cytokine gene expression and papilloma growth
      during murine multistage carcinogenesis by pentoxifylline.
AB  - Topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to the dorsal
      epidermis of Sencar mice induces synthesis of pro-inflammatory cytokines,
      including interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF
      alpha). These proteins differentially regulate proliferation of epidermal
      keratinocytes, as well as stimulate chemotaxis, migration and production of
      reactive oxygen and nitrogen intermediates by leukocytes. Studies over the past
      several years have demonstrated that pentoxifylline ([1-(5-oxohexyl)-3,7-dimethyl
      xanthine], oxpentifylline), which is a methylxanthine derivative used clinically
      for treatment of vascular insufficiency, has the unique ability to inhibit
      synthesis of pro-inflammatory cytokines. The present studies were performed to
      examine the effects of acute and chronic administration of pentoxifylline on TPA
      induced cutaneous inflammation in female Sencar mice treated once with 10
      micrograms TPA and also to determine the ability of pentoxifylline to inhibit the
      tumor promotion process in mice treated with a single application of 25 nmol 7,12
      dimethylbenz[a]anthracene (DMBA) followed for 8 weeks by twice weekly topical
      application of TPA. Intraperitoneal injection of 50 micrograms/g pentoxifylline
      at 30 min prior to topical application of 10 micrograms TPA to the dorsal
      epidermis of Sencar mice inhibited TPA-induced IL-1 alpha and TNF-alpha gene
      expression 24 h after TPA treatment. Administration of pentoxifylline also
      significantly inhibited all parameters of acute TPA-induced inflammatory response
      examined 24 h later, including skin thickening (P < 0.005), infiltration of
      neutrophils into the dermis (P < 0.001), the corresponding dermal myeloperoxidase
      activity (P < 0.01) and epidermal hyperplasia (P < 0.001). Injection of 50
      micrograms/g pentoxifylline over an 8 week time period significantly inhibited
      DMBA/TPA-induced papilloma growth (P < 0.05). These results indicate that
      administration of pentoxifylline is an effective means of inhibiting acute TPA
      induced cutaneous inflammation and pro-inflammatory cytokine gene expression, as
      well as is effective as an antipromoter that inhibits papilloma growth.

PMID- 8761433
TI  - Recombinant rat and hamster N-acetyltransferases-1 and -2: relative rates of N
      acetylation of arylamines and N,O-acyltransfer with arylhydroxamic acids.
AB  - Genes for the 290 amino acid, 33-34 kDa cytosolic acetyltransferases (NAT1* and
      NAT2*) from rat and hamster were cloned and expressed in Escherichia coli. Active
      clones were selected by a simple visual test for their ability to decolorize 4
      aminoazobenzene in bacterial medium by acetylation. These recombinant
      acetyltransferases were analyzed for: (i) N-acetyltransferase, which was assayed
      by the rate of acetyl coenzyme A-dependent N-acetylation of 2-aminofluorene (2
      AF) or 4-aminoazobenzene (AAB); (ii) arylhydroxamic acid acyltransferase, assayed
      by N,O-acyltransfer with N-hydroxy-N-acetyl-2-aminofluorene. Both NAT2s showed
      first order increases in N-acetylation rates with increasing 2-AF or AAB
      concentrations between 5 and 100 microM, with apparent K(m) values of 22-32 and
      62-138 microM respectively. Although under the same conditions the N-acetylation
      rates for the two NAT1s declined by > 50%, below 5 microM 2-AF or AAB, the NAT
      rate data fit Michaelis-Menten kinetics, and the apparent K(m) values were 0.2
      0.9 microM. For N,O-acyltransferase, the apparent K(m) values of the NAT1s were
      approximately 6 microM, while the K(m) values of the NAT2s were approximately 20-
      to 70-fold higher. SDS-PAGE/Western blot analysis of the recombinant
      acetyltransferases gave apparent relative molecular weights (MWr) of
      approximately 31 kDa for both NAT1s and rat NAT2 and approximately 29 kDa for
      hamster NAT2. Comparable MWr values were observed for native hamster liver NAT1
      and NAT2 and for rat NAT1 under the same conditions. Although we did not detect
      NAT2-like activity in rat liver cytosol previously, the present data show that
      the rat NAT2* gene does code for a functional acetyltransferase, with properties
      similar to those of hamster liver NAT2. The data also indicate that at low
      substrate concentrations, NAT1 would apparently play the predominant role in vivo
      in N-acetylation and N,O-acyltransfer of aromatic amine derivatives, including
      their metabolic activation to DNA-reactive agents.

PMID- 8761434
TI  - Activation of K-ras in aflatoxin B1-induced lung tumors from AC3F1 (A/J x
      C3H/HeJ) mice.
AB  - In addition to being a potent hepatocarcinogen, aflatoxin B1 (AFB1) is a
      pulmonary carcinogen in experimental animals and epidemiological studies have
      shown an association between AFB1 exposure and lung cancer in humans. Since point
      mutations at codons 12, 13 and 61 of the K-ras protooncogene are often implicated
      in chemically induced mouse lung tumors and in human lung adenocarcinomas, we
      undertook an investigation of the role of K-ras activation in AFB1-induced
      pulmonary carcinogenesis. Female AC3F1 (A/J x C3H/HeJ) mice were treated with
      AFB1 (150 mg/kg i.p., divided into 24 doses over 8 weeks), and 6-14 months after
      the completion of dosing mice were killed and pulmonary adenomas and carcinomas
      removed. Of the 76 AFB1-induced lung tumors analyzed by single strand
      conformation polymorphism (SSCP) and direct sequencing, 75 possessed K-ras codon
      12 mutations (46 GTT, 14 GAT, 13 TGT and 2 TTT; normal, GGT) and one had a GGC-
      >CGC mutation in codon 13. The observation that K-ras mutations occurred only at
      G:C base pairs is in agreement with N7-guanine being the primary site of AFB1-DNA
      adduct formation and with guanine residues being targets for AFB1-induced
      oxidative DNA damage via formation of 8-hydroxydeoxyguanosine (8-OHdG). The AFB1
      specific nature of the observed K-ras mutation spectrum and the fact that 100% of
      the tumor samples examined contained K-ras mutations is consistent with K-ras
      activation being an early, critical event in AFB1-induced pulmonary
      carcinogenesis in AC3F1 mice. The parental origin of the observed K-ras mutations
      was determined by allele-specific PCR amplification of AFB1-induced lung tumor
      DNA followed by SSCP analysis. In the vast majority of tumors (73/76), the
      mutated K-ras allele was derived from the lung tumor susceptible A/J parent. This
      finding supports the existence of a link between K-ras and differences in mouse
      lung tumor susceptibility.

PMID- 8761435
TI  - Cell proliferation and apoptosis during mammary carcinogenesis in pituitary
      isografted mice.
AB  - In the present study, pituitary isografted animals serve as a model for
      evaluating the changes in differentiation, cell proliferation and programmed cell
      death (apoptosis) in mammary epithelial cells during carcinogenesis. The
      percentage of bromodeoxyuridine (BrdU)-labeled ductal and alveolar cells was
      significantly higher in pituitary isografted animals than in non-isografted
      control animals. BrdU-labeled cells increased in lobular hyperplastic nodules,
      keratinized nodules and mammary carcinomas; similar changes were observed with
      apoptotic cells, which were rare in mammary glands of adult non-isografted
      animals (one to three apoptotic cells per 2000 mammary epithelial cells), but
      their number increased in hyperplastic lesions and mammary carcinomas. Among
      hyperplastic nodular lesions, variants with high, moderate and low proliferative
      activity and/or apoptotic cell death were identified, which suggests that they
      may have different growth potentials and different propensities for malignant
      transformation. After removing pituitary isografts, apoptosis occurs in
      hyperplastic lesions but not in mammary carcinomas-implying that malignant tumors
      are hormone-independent. The dynamics of the changes in apoptotic cell death
      among various hyperplastic lesions after removal of pituitary isografts suggests
      that these lesions are composed of heterogeneous cell populations, as far as the
      initiation of apoptosis is concerned. Our data indicate that apoptosis can be
      used together with cell proliferation as a potential marker in characterizing the
      growth potential and phenotypic diversity of hyperplastic, premalignant and
      malignant mammary gland lesions.

PMID- 8761436
TI  - Production of 8-hydroxy-2'-deoxguanosine in DNA by microsomal activation of
      tamoxifen and 4-hydroxytamoxifen.
AB  - Using rat liver microsomal preparations, we have investigated the activation of
      the anti-estrogen compound tamoxifen (TAM) and its metabolite 4-hydroxytamoxifen
      (4-OH-TAM) to form 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in DNA. When reduced
      nicotinamide adenine dinucleotide phosphate (NADPH) was used as a cofactor in
      microsomal activation of either TAM or 4-OH-TAM, the levels of 8-OH-dG were 3
      fold higher than in microsomes plus cofactor only. In contrast, no significant
      increase in the level of 8-OH-dG was detected in DNA samples from microsomal
      activation of either TAM or 4-OH-TAM with cumene hydroperoxide as the cofactor.
      These results demonstrate that the microsomal activation of TAM and 4-OH-TAM to
      form 8-OH-dG is dependent upon the cofactor used. The addition of either EDTA or
      catalase to the activation system significantly decreased the formation of 8-OH
      dG by TAM, but not by 4-OH-TAM. The presence of either sodium azide, superoxide
      dismutase or mannitol inhibited the formation of 8-OH-dG by both TAM and 4-OH
      TAM. Taken together these findings indicate that microsomal activation of TAM and
      4-OH-TAM with NADPH generates reactive oxygen species which result in the
      formation of 8-OH-dG. We propose that the formation of 8-OH-dG by TAM and its
      metabolites may contribute to the observed carcinogenic effects of TAM.

PMID- 8761437
TI  - Malignant conversion of human cells by antisense cDNA to a putative tumor
      suppressor gene.
AB  - A cell line, SCC83-01-82, derived from a human oral squamous carcinoma, was non
      tumorigenic in nude mice, a characteristic of premalignant cells. Conversion of
      these cells to a tumorigenic phenotype with chemical mutagens did not increase
      mutations in hot spots or other conserved regions of p53 or H-ras genes.
      Investigation of the tumorigenic conversion using an expression library resulted
      in isolation of a previously unidentified gene, CATR1, located on the long arm of
      chromosome 7 at band approximately q31-32. Evidence for the involvement of this
      gene in conversion to tumorigenicity was demonstrated by introduction of a
      eukaryotic expression CATR1 construct into SCC83-01-82 cells. Transfection with
      the antisense construct reduced the expression of CATR1 in tumors formed by the
      transfected cells, suggesting that the antisense suppression of endogenous CATR1
      expression appeared to be sufficient for tumorigenic conversion. These results
      are consistent with previous reports of cytogenetic analyses of tumors, that 7q31
      32 contains a gene(s) with tumor suppressor activity; CATR1 is a candidate for
      this putative suppressor gene.

PMID- 8761438
TI  - Sulindac suppresses tumorigenesis in the Min mouse.
AB  - The Min mouse provides a genetically defined model for inherited and sporadic
      forms of human colorectal tumorigenesis. To test the suitability of this model
      for the evaluation and optimization of chemopreventive agents, we examined the
      effects of sulindac on tumorigenesis in Min mice as this compound can inhibit
      colorectal tumorigenesis in human familial adenomatous polyposis patients.
      Treatment of Min mice with sulindac in their drinking water (84 mg/l) or diet
      (167 and 334 p.p.m.) resulted in a significantly decreased average tumor load.
      The conservation of sulindac activity in the Min mouse provides an opportunity to
      explore the mechanism of sulindac suppression as well as to test other potential
      chemopreventive agents.

PMID- 8761439
TI  - Human connexin 37 is polymorphic but not mutated in tumours.
AB  - Connexins are phylogenetically conserved proteins responsible for gap junctional
      intercellular communication (GJIC). In tumours, GJIC is frequently disrupted. We
      have tested the hypothesis that the connexin 37 (Cx37) gene might be mutated in
      human tumours from tissues in which the Cx37 gene is known to be expressed. Eight
      lung adenocarcinomas and 18 sporadic breast carcinomas were analysed. While most
      tumours had GTA at codon 130, a base change GTA-->ATA converting valine into
      isoleucine was found in three breast cancers (one homozygous for ATA) and two
      lung tumour samples. However, screening of normal DNA from the same patients and
      DNA from 42 healthy donors revealed that such base change also exists in normal
      tissue. Thus, we conclude that there is polymorphism of the connexin 37 gene in
      the human population. This is the first finding of polymorphism in the connexin
      gene family.

PMID- 8761440
TI  - The BN rat strain carries dominant hepatocarcinogen resistance loci.
AB  - The phylogenetically distant F344 and BN rat strains and their (BN x F344) F1
      hybrids were compared for susceptibility to hepatocarcinogenesis using the
      'resistant hepatocyte' model. Quantitative stereological analysis of frequency
      (number/liver) and size (mean volume and volume fraction) of placental form
      glutathione S-transferase (GST-P)-positive lesions was carried out at 8, 15 and
      32 weeks after diethylnitrosamine initiation. The number/liver of GST-P-positive
      lesions at any time point was slightly higher in BN and (BN x F344) F1 rats than
      in F344 rats, but not statistically different. However, mean volume and volume
      fraction of GST-P positive lesions were much higher in F344 than in both BN and
      (BN x F344) F1 rats at any time point, with a difference of up to > 10-fold. GST
      P-positive lesions exhibited a significantly higher labeling index and much lower
      remodeling in male F344 than in BN and (BN x F344) F1 rats. HCCs were present at
      54-57 weeks after initiation in 77% of male F344 and in no (BN x F344) F1 rats
      and at 70 weeks HCCs were observed in 100% of male F344 and in 23% of (BN x F344)
      F1 rats. These results suggest that the BN rat strain is resistant to
      hepatocarcinogenesis and that its resistance is genetically transmitted as a
      dominant character to F1 hybrids of the BN strain with the F344 susceptible
      strain.

PMID- 8761441
TI  - Metabolic activation and DNA binding of food mutagens and other environmental
      carcinogens in human mammary epithelial cells.
AB  - Cultures of human mammary epithelial cells were treated with one of seven
      heterocyclic amine food mutagens [2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2
      amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-di
      methylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5
      f]quinoxaline (4,8-DiMeIQx), 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline
      (7,8-DiMeIQx), 2-amino-3,4,7,8-tetramethylimidazo[4,5-f]quinoxaline (4,7,8
      TriMeIQx) or 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP)], four
      nitropyrenes (1-nitropyrene (1-NP), 1,3-dinitropyrene (1,3-DNP), 1,6
      dinitropyrene (1,6-DNP) or 1,8-dinitropyrene (1,8-DNP)] or the polycyclic
      aromatic hydrocarbon dibenzo[a,l]pyrene (DB[a,l]P). DNA isolated from the
      cultures was analysed by 32P-post-labelling and in each case the presence of
      carcinogen-DNA adducts was detected. The patterns and numbers of adducts obtained
      when human mammary cell DNA digests were separated on polyethyleneimine-cellulose
      TLC were found to closely resemble those previously demonstrated to be present in
      the DNA of tissues from rodents and other primates treated with the same agents.
      Up to six DNA adducts were detected in human breast cells treated with IQ and
      MeIQ. Fewer adducts (1-3) were detected following treatment with MeIQx or its
      methylated derivatives, whilst PhIP gave rise to at least four distinct adduct
      spots. Five adduct spots were detected in breast cells treated with DB[a,l]P or
      with 1-NP, but fewer adduct spots were formed by 1,3-, 1,6- and 1,8-DNP. These
      data demonstrate the ability of human breast epithelial cells to activate to DNA
      binding species a range of carcinogenic compounds known to be present in the
      human diet or to which humans are known to be exposed environmentally.

PMID- 8761442
TI  - Benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide adducts in native and denatured
      DNA.
AB  - High performance liquid chromatography/UV-absorption and 32P-postlabeling were
      used to quantitate adducts generated by reaction of the four configurationally
      isomeric benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxides with native or
      denatured DNA in vitro. For both the 4R, 3S-dihydrodiol 2S,1R-epoxide and the
      4S,3R-dihydrodiol 2S,1R-epoxide, the amount of product resulting from trans
      opening of the epoxide ring by the exocyclic amino group of deoxyadenosine in
      denatured DNA was much less than the level found in native DNA, indicating that
      the native DNA structure probably intercalates the hydrocarbon residue in a
      fashion that promotes adenine reaction for 2S,1R-epoxides.

PMID- 8761443
TI  - The relationship between megacolon and carcinoma of the colon: an experimental
      approach.
AB  - 'Carcinoma of the colon does not occur in cases of megacolon' is an axiom held by
      Brazilian physicians working in endemic areas for Chagas' disease. The objective
      of the present study was to test this axiom experimentally by submitting rats
      with experimental megacolon to a carcinogen which causes carcinoma of the colon.
      Eighty young male Wistar rats received serosal application of either saline (0.9%
      NaCl) or 2 mM benzalkonium chloride (BAC) to the distal colon. Ten months later
      randomly chosen saline and BAC rats were injected weekly with dimethylhydrazine
      (DMH) for 20 weeks. Non-DMH-treated rats from both original groups were
      maintained, for a total of four experimental groups. Three months after the
      injections all surviving rats were killed. At autopsy the presence of absence of
      carcinomas along the colon was recorded. The induction of megacolon was evaluated
      by morphometry of the wall from the distal colon and myenteric denervation was
      assessed by neuron counts. An increase of at least 2-fold in distal colon wall
      thickness confirmed the induction of megacolon in BAC-treated rats. Neuronal
      counts from BAC and control rats not treated with DMH showed an average
      denervation of 63%. The number of distal colon carcinomas in BAC+DMH-treated rats
      was significantly lower than that in DMH-treated rats. These findings appear to
      contradict the traditional concept of carcinogenesis of the colon. The clinical
      axiom was reproduced experimentally.

PMID- 8761445
TI  - Muscle-specific overexpression of lipoprotein lipase in transgenic mice results
      in increased alpha-tocopherol levels in skeletal muscle.
AB  - Lipoprotein lipase (LPL) has been implicated in the delivery of chylomicron
      located alpha-tocopherol (alpha-TocH) to peripheral tissues. To investigate the
      role of LPL in the cellular uptake of alpha-TocH in peripheral tissue in vivo,
      three lines of transgenic mice [mouse creatine kinase- (MCK) L, MCK-M and MCK-H]
      expressing various amounts of human LPL were compared with regard to alpha-TocH
      levels in plasma, skeletal muscle, cardiac muscle, adipose tissue and brain.
      Depending on the copy number of the transgene, LPL activity was increased 3- to
      27-fold in skeletal muscle and 1.3- to 3.7-fold in cardiac muscle. The
      intracellular levels of alpha-TocH in skeletal muscle were significantly
      increased in MCK-M and MCK-H animals and correlated highly with the tissue
      specific LPL activity (r = 0.998). The highest levels were observed in MCK-H
      (21.4 nmol/g) followed by MCK-M (13.3 nmol/g) and MCK-L (8.2 nmol/g) animals when
      compared with control mice (7.3 nmol/g). Excellent correlation was also observed
      between intracellular alpha-TocH and non-esterified fatty acid (NEFA) levels (r =
      0.998). Although LPL activities in cardiac muscle were also increased in the
      transgenic mouse lines, alpha-TocH concentrations in the heart remained
      unchanged. Similarly, alpha-TocH levels in plasma, adipose tissue and brain were
      unaffected by the tissue specific over-expression of LPL in muscle. The
      transgenic model presented in this report provides evidence that the uptake of
      alpha-TocH in muscle is directly dependent on the level of LPL expression in
      vivo. Increased intracellular alpha-TocH concentrations with increased
      triglyceride lipolysis and NEFA uptake might protect the myocyte from oxidative
      damage during increased beta-oxidation.

PMID- 8761444
TI  - The lipocalin protein family: structure and function.
AB  - The lipocalin protein family is a large group of small extracellular proteins.
      The family demonstrates great diversity at the sequence level; however, most
      lipocalins share three characteristic conserved sequence motifs, the kernel
      lipocalins, while a group of more divergent family members, the outlier
      lipocalins, share only one. Belying this sequence dissimilarity, lipocalin
      crystal structures are highly conserved and comprise a single eight-stranded
      continuously hydrogen-bonded antiparallel beta-barrel, which encloses an internal
      ligand-binding site. Together with two other families of ligand-binding proteins,
      the fatty-acid-binding proteins (FABPs) and the avidins, the lipocalins form part
      of an overall structural superfamily: the calycins. Members of the lipocalin
      family are characterized by several common molecular-recognition properties: the
      ability to bind a range of small hydrophobic molecules, binding to specific cell
      surface receptors and the formation of complexes with soluble macromolecules. The
      varied biological functions of the lipocalins are mediated by one or more of
      these properties. In the past, the lipocalins have been classified as transport
      proteins; however, it is now clear that the lipocalins exhibit great functional
      diversity, with roles in retinol transport, invertebrate cryptic coloration,
      olfaction and pheromone transport, and prostaglandin synthesis. The lipocalins
      have also been implicated in the regulation of cell homoeostasis and the
      modulation of the immune response, and, as carrier proteins, to act in the
      general clearance of endogenous and exogenous compounds.

PMID- 8761446
TI  - Measurement of oxidized and methylated DNA bases by HPLC with electrochemical
      detection.
AB  - Oxidative DNA damage is thought to be an important contributor to cancer
      development and to be affected by dietary constituents, so its accurate
      measurement is important. DNA methylation is recognized as an important mechanism
      affecting gene expression. In the present paper we describe an HPLC-with
      electrochemical-detection procedure that allows rapid and sensitive measurement
      of four oxidized (2,6-diamino-4-hydroxy-5-formamidopyrimidine, 5-hydroxyuracil, 8
      hydroxyguanine, 8-hydroxyadenine) and three methylated (7-methylguanine, 1
      methylguanine, O6-methylguanine) bases in acid hydrolysates of DNA. Guanine was
      also detected, but was clearly separated from the other bases.

PMID- 8761447
TI  - The chemical mechanism of beta-haematin formation studied by Mossbauer
      spectroscopy.
AB  - Spontaneous formation of beta-haematin (malaria pigment) from haematin in acetate
      solution follows pseudo-zero-order and not autocatalytic kinetics. Acetate
      appears to facilitate the reaction by solubilizing the haematin and acting as a
      phase-transfer catalyst, a role which, in vivo, could be fulfilled by carboxylic
      acids or amino acids.

PMID- 8761448
TI  - The role of lipoprotein lipase and apoprotein E in the recognition of
      chylomicrons and chylomicron remnants by cultured isolated mouse hepatocytes.
AB  - Lipoprotein lipase (LPL) has been proposed to play a role in the uptake of
      chylomicron remnants by hepatocytes by mediating the binding of these
      lipoproteins to cell-surface glycosaminoglycans and to the low-density
      lipoprotein receptor-related protein (LRP). This proposal is based on studies
      that examined the binding of chylomicrons to HepG2 cells, fibroblasts and Chinese
      hamster ovary cells in culture, in the presence of large amounts of LPL
      [Beisiegel (1995) Curr. Opin. Lipidol. 6, 117-122]. We have investigated whether
      LPL attached to the surface of chylomicrons enhances the binding and uptake of
      these lipoproteins to isolated hepatocytes maintained in culture. Bovine milk LPL
      was bound to mouse chylomicrons, double-labelled in vivo with [3H]retinol (in
      retinyl esters) and with [14C]palmitic acid (in triacylglycerols), collected from
      the mesenteric lymph of normal mice and from mice lacking the apoprotein E (apo
      E) gene. Normal chylomicrons (containing apo E) and apo E-free chylomicrons, with
      or without bound LPL, were incubated with cultured hepatocytes isolated from mice
      lacking the apo E gene. At 0 degree C LPL did not enhance the binding of the
      normal or apo E-free chylomicrons by the hepatocytes. When incubations were
      performed at 37 degrees C the triacylglycerols of normal and apo E-free
      chylomicrons were hydrolysed by LPL and there was a significant uptake of
      [14C]fatty acids and [3H]retinol by the hepatocytes. The addition of heparin or
      lactoferrin, a known inhibitor of hepatic uptake of chylomicron remnants, to the
      incubation medium inhibited the uptake of [3H]retinol, present in the lipoprotein
      core, but not the uptake of the [14C]fatty acids. We conclude that: (1) LPL
      attached to chylomicrons in amounts sufficient to effectively hydrolyse their
      core triacylglycerols does not enhance the binding of these lipoproteins to the
      surface of isolated hepatocytes; (2) the recognition and uptake of chylomicrons
      by hepatocytes requires that these lipoproteins be first hydrolysed by LPL; and
      (3) the uptake of lipolysed chylomicrons (remnants) by hepatocytes does not
      require the mediation of apo E.

PMID- 8761449
TI  - Prion diseases and the 'protein only' hypothesis: a theoretical dynamic study.
AB  - In the 'protein only' hypothesis, prion diseases are thought to result from the
      conformational change of a normal isoform of a prion protein (PrPC) to a protease
      resistant, pathogenic form called PrPSc. This conversion rests on an
      autocatalytic process requiring the presence of pre-existing PrPSc. Theoretical
      kinetic analysis of the dynamic process, including the turnover of the normal
      prion protein, shows that the system exhibits bistability properties, indicating
      that the very slow accumulation of the abnormal form of the protein in the brain
      could in fact be the consequence and not the cause of the disorders. The cause
      would be a transition between two alternative steady states of the system. The
      presence of a small amount of the PrPSc protein in lymphocytes does not
      necessarily constitute any indication of a non-symptomatic but infectious
      pathogenic state. Moreover, infectious prion particles should not be seen as
      necessarily composed of the abnormal isoform of the protein, as usually stated.
      Particles containing only an excess of the normal form of the protein might also
      be pathogenic. Compounds that can act on the turnover rate of the normal PrPC
      protein could be a therapeutic strategy against prion diseases.

PMID- 8761450
TI  - Focal adhesion kinase (pp125FAK) cleavage and regulation by calpain.
AB  - Focal adhesion kinase (125 kDa form; pp125FAK) is a widely expressed non-receptor
      tyrosine kinase that is implicated in integrin-mediated signal transduction. We
      have identified a novel means of pp 125FAK regulation in human platelets, in
      which this kinase undergoes sequential proteolytic modification from the native
      125 kDa form to 90, 45 and 40 kDa fragments in thrombin-, collagen- and ionophore
      A23187-stimulated platelets. The proteolysis of pp125FAK was prevented by
      pretreating platelets with the calpain inhibitors calpeptin or calpain inhibitor
      1, and was reproduced in vitro by incubating immunoprecipitated pp125FAK with
      purified calpain. Proteolysis of pp125FAK resulted in a dramatic reduction in its
      autokinase activity and led to its dissociation from the cytoskeletal fraction of
      platelets. These studies define a novel signal-terminating role for calpain,
      wherein proteolytic modification of pp125FAK attenuates its autokinase activity
      and induces its subcellular relocation within the cell.

PMID- 8761451
TI  - Interleukin 2 is a lectin that associates its receptor with the T-cell receptor
      complex.
AB  - To determine the nature of the mechanism by which the binding of interleukin-2
      (IL-2) to its receptor (IL-2R beta) induces IL-2R beta phosphorylation by the
      tyrosine kinase p56lck associated with the T-cell receptor (TCR) complex, we
      investigated the possibility that this mechanism was due to the putative lectin
      activity of IL-2 ([Sherblom, Sathyamoorthy, Decker and Muchmore (1989) J.
      Immunol. 143, 939-944]. Here we demonstrate that IL-2 is a calcium-independent
      lectin specific for oligomannosidic N-glycans with five and six mannose residues.
      This lectin activity is preserved after binding of IL-2 to IL-2R beta. IL-2
      behaves as a bifunctional molecule that associates IL-2R beta with specific
      glycoprotein ligands of the TCR complex including a glycosylated form of CD3.

PMID- 8761452
TI  - Compartment-specific regulation of phosphoinositide 3-kinase by platelet-derived
      growth factor and insulin in 3T3-L1 adipocytes.
AB  - To understand how the stimulation of phosphoinositide 3-kinase (PI 3-kinase) by
      different growth factors can activate different subsets of downstream responses,
      growth-factor regulation of PI 3-kinase activity at different intracellular
      locations was investigated in 3T3-L1 adipocytes. Insulin caused a large
      stimulation of glucose transport and stimulated recruitment of transferrin
      receptors to the plasma membrane (PM) in these cells, whereas platelet-derived
      growth factor (PDGF)-bb was virtually without effect on these responses.
      Subcellular fractionation studies after stimulation with PDGF-bb or insulin
      revealed a differential effect of these growth factors on subcellular
      localization of PI 3-kinase activity. PDGF was more effective than insulin in
      stimulating PI 3-kinase activity and recruiting the p85 alpha PI 3-kinase adaptor
      subunit in the fraction containing the PM. However, in the microsomal fraction
      insulin significantly increased PI 3-kinase activity and p85 alpha levels,
      whereas PDGF was almost without effect. In the microsomal membrane fraction the
      insulin-stimulated recruitment of p85 alpha closely matched the increase PI 3
      kinase activity, indicating that insulin stimulation of PI 3-kinase in this
      fraction is largely due to recruitment of PI 3-kinase enzyme rather than
      alterations in specific activity. Insulin-stimulated recruitment of p85 alpha to
      the microsomal membranes was not inhibited by wortmannin, indicating that PI 3
      kinase activity was not required for this process. A further level of compartment
      specific regulation of PI 3-kinase in response to PDGF was revealed by the
      finding that tyrosine phosphorylation of the p85 alpha adaptor was restricted to
      the PM-containing fraction. Insulin had no effect on p85 tyrosine phosphorylation
      in either fraction. In summary, these results suggest a basis by which insulin
      and PDGF could both use PI 3-kinase signalling cascades but achieve different
      signalling outcomes.

PMID- 8761453
TI  - The inositol 1,4,5-trisphosphate-gated Ca2+ channel: effect of the protein thiol
      reagent thimerosal on channel activity.
AB  - The solubilized partially purified Ins(1,4,5)P3-sensitive Ca2+ channel from rat
      cerebellum has been reconstituted into planar lipid bilayer membranes by the 'tip
      dip' method [Ehrlich (1992) Methods Enzymol. 207, 463-471] allowing low noise
      current records. Single-channel events have been recorded. In the presence of 10
      microM Ins(1,4,5)P3, 50 microM ATP, and 0.2 microM Ca2+ the Ins(1,4,5)P3 receptor
      channel opens to a conductance level of 53 pS. In the presence of 100 microM
      thimerosal (TMS), a sulphydryl-oxidizing agent, three subconductance levels (60
      pS, 80 pS and 120 pS) were observed. More than one population of mean open times
      was found, both in the absence and presence of TMS, although TMS affected the
      length of the open time by decreasing the short opening significantly from 4.05
      ms to 2.78 ms and increasing the longer open time from 27.8 ms to 94.8 ms. The
      results indicate that TMS enhances Ins(1,4,5)P3-induced Ca2+ release by both
      altering the open times of the channel significantly and causing a shift to
      higher subconductance levels.

PMID- 8761454
TI  - Characterization of a ferritin mRNA from Arabidopsis thaliana accumulated in
      response to iron through an oxidative pathway independent of abscisic acid.
AB  - A ferritin cDNA, AtFer1, from seedlings of Arabidopsis thaliana has been
      characterized. The deduced amino acid sequence of the AtFer1 protein indicates
      that A. thaliana ferritin shares the same characteristics as the plant ferritin
      already characterized from the Leguminosae and Graminacea families: (i) it
      contains an additional sequence in its N-terminal part composed of two domains: a
      transit peptide responsible for plastid targeting and an extension peptide; (ii)
      amino acids that form the ferroxidase centre of H-type animal ferritin, as well
      as Glu residues characteristic of L-type animal ferritin, are conserved in
      AtFer1; (iii) the C-terminal part of the A. thaliana ferritin subunit defining
      the E-helix is divergent from its animal counterpart, and confirms that 4-fold
      symmetry axis channels are hydrophilic in plant ferritin. Southern blot
      experiments indicate that AtFer1 is likely to be encoded by a unique gene in the
      A. thaliana genome, although a search in the NCBI dbEST database indicates that
      other ferritin genes, divergent from AtFer1, may exist. Iron loading of A.
      thaliana plantlets increased ferritin mRNA and protein abundance. In contrast to
      maize, the transcript abundance of a gene responding to abscisic acid (RAB18) did
      not increase in response to iron loading treatment, and A. thaliana ferritin mRNA
      abundance is not accumulated in response to a treatment with exogenous abscisic
      acid, at least in the culture system used in this study. In addition, iron
      induced increases in ferritin mRNA abundance were the same as wild-type plants in
      abi1 and abi2 mutants of A. thaliana, both affected in the abscisic acid response
      in vegetative tissues. Increased AtFer1 transcript abundance in response to iron
      is inhibited by the antioxidant N-acetylcysteine. These results indicate that an
      oxidative pathway, independent of abscisic acid, could be responsible for the
      iron induction of ferritin synthesis in A. thaliana.

PMID- 8761455
TI  - Characterization of the rat glutathione S-transferase Yc2 subunit gene, GSTA5:
      identification of a putative antioxidant-responsive element in the 5'-flanking
      region of rat GSTA5 that may mediate chemoprotection against aflatoxin B1.
AB  - We have isolated and characterized genomic DNA encoding the rat glutathione S
      transferase Yc2 subunit. This protein is now referred to as rGSTA5 and is
      noteworthy because of its high activity towards aflatoxin B1-8,9-epoxide, its
      marked inducibility by chemoprotectors, its sex-specific regulation, and its over
      expression in hepatoma and preneoplastic nodules. The rGSTA5 gene, which was
      isolated on two overlapping bacteriophage lambda clones, is approx. 12 kb in
      length and, unlike other class Alpha genes described to date, it comprises six
      exons. The transcription start site has been identified 228 bp upstream from the
      ATG translational initiation codon, and is situated 51 bp downstream from a
      consensus TATA-box. Deletion analysis, using luciferase reporter constructs, has
      shown that the region between -177 bp and +65 bp from the transcriptional start
      site contains a functional promoter. Computer-assisted analysis of the upstream
      sequence has indicated the presence of an antioxidant-responsive element (ARE),
      and several elements thought to be required for tissue-specific expression of the
      enzyme. In addition, several putative oestrogen-responsive half sites were
      observed in both upstream and intronic sequences.

PMID- 8761456
TI  - Effects of insulin on the regulation of branched-chain alpha-keto acid
      dehydrogenase E1 alpha subunit gene expression.
AB  - Alterations in dietary intake, especially of protein, may produce changes in the
      hepatic levels of the branched-chain alpha-keto acid dehydrogenase (BCKAD)
      complex. The possible role of insulin in the regulation of these observed changes
      in hepatic capacity for BCKAD expression was therefore examined. Steady-state RNA
      levels encoding three of the subunits, E1 alpha, E1 beta and E2, increased by 2-4
      fold in the livers of mice starved for 3 days, a known hypoinsulinaemic state. In
      contrast, the levels of E1 beta and E2, but not E1 alpha, RNA were decreased when
      mice were fed 0% protein diets compared with the levels observed in mice fed
      standard (23%) or higher protein isocaloric diets. BCKAD subunit protein levels
      under these conditions changed co-ordinately even though the changes in RNA were
      not co-ordinate. The effects of hormonal changes that might be associated with
      these dietary changes were examined, using the rodent hepatoma cell line H4IIEC3.
      In these cells, the levels of E1 alpha protein and mRNA were significantly
      depressed in the presence of insulin. In contrast, the levels of E1 beta and E2
      RNAs were not decreased by insulin. The half-lives of the E1 alpha and E2 RNAs
      were determined to be quite long, from 13 to 18 h, with insulin having no
      dramatic overall effect on the half-lives determined over 24 h. Therefore, it is
      likely that insulin directly affects the transcription of the E1 alpha gene
      rather than RNA stability in exerting its negative regulatory effect. This effect
      is specific to the E1 alpha subunit. The differences in BCKAD subunit RNA levels
      observed under various nutritional and developmental conditions may therefore be
      the result of the differential effects of insulin and other hormones on the
      multiple regulatory mechanisms modulating BCKAD subunit expression.

PMID- 8761457
TI  - NMR solution conformation of heparin-derived tetrasaccharide.
AB  - The solution conformation of the homogeneous, heparin-derived tetrasaccharide
      delta UA2S(1-->4)-alpha-D-GlcNpS6S(1-->4)-alpha-L-IdoAp2S (1-->4)-alpha-D
      GlcNpS6S (residues A, B, C and D respectively, where IdoA is iduronic acid) has
      been investigated by using 1H- and 13C-NMR. Ring conformations have been defined
      by J-coupling constants and inter-proton nuclear Overhauser effects (NOEs), and
      the orientation of one ring with respect to the other has been defined by inter
      ring NOEs. NOE-based conformational modelling has been done by using the
      iterative relaxation matrix approach (IRMA), restrained molecular dynamics
      simulations and energy minimization to refine structures and to distinguish
      between minor structural differences and equilibria between various ring forms.
      Both glucosamine residues B and D are in the 4C1 chair conformation. The 6-O
      sulphate group is oriented in the gauche-trans configuration in the D ring,
      whereas in the B ring the gauche-gauche rotomer predominates. Uronate (A) and
      iduronate (C) residues are mostly represented by 1H2 and 2S0 twisted boat forms,
      respectively, with small deviations in expected coupling constants and NOEs
      suggesting minor contributions from other A and C ring conformations.

PMID- 8761458
TI  - The role of a H(+)-ATPase in the regulation of cytoplasmic pH in Trypanosoma
      cruzi epimastigotes.
AB  - Cytoplasmic pH (pHi) regulation was studied in Trypanosoma cruzi epimastigotes
      using fluorescent probes. Steady-state pHi was maintained even in the absence of
      extracellular Na+ or K+, but was significantly decreased in the absence of Cl-.
      Acid-loaded epimastigotes regained normal pHi by a process that was ATP-dependent
      and sensitive to N-ethylmaleimide, dicyclohexyl-carbodi-imide and
      diethylstiboestrol, suggesting involvement of a H(+)-pumping ATPase. Recovery
      from an acid load was independent of extracellular Na+ or K+ and insensitive to
      omeprazole, vanadate and low concentrations of bafilomycin A1. Using the
      fluorescent probe bisoxonol to measure the membrane potential of intact cells,
      acid loading of epimastigotes was shown to result in a dicyclohexylcarbodi-imide
      sensitive hyperpolarization, which suggests electrogenic pumping of protons
      across the plasma membrane. Addition of glucose, but not of 6-deoxyglucose,
      produced a transient cellular acidification of possible metabolic origin, and
      increased the rate of recovery from an acid load. Taken together, these results
      are consistent with an important role of a H(+)-ATPase in the regulation of pHi
      homoeostasis in T. cruzi.

PMID- 8761459
TI  - Isolation and characterization of nitrogenase MoFe protein from the mutant strain
      pHK17 of Klebsiella pneumoniae in which the two bridging cysteine residues of the
      P-clusters are replaced by the non-coordinating amino acid alanine.
AB  - Nitrogenase MoFe protein (Kp1) from the mutant strain pHK17 or Klebsiella
      pneumoniae has been purified to give three catalytically active fractions. In
      this mutant, each of the two bridging cysteine ligands to the P-clusters, alpha
      Cys-89 and beta-Cys-94, has been replaced by a non-coordinating residue, alanine.
      SDS/PAGE and earlier native gels showed that the three fractions retained the
      normal alpha 2 beta 2 tetrameric form of wild-type Kp1; therefore we conclude
      that in each of the fractions the subunits are folded differently, thus resulting
      in different surface charges and allowing separation of the fractions on ion
      exchange chronatography. Earlier EPR and magnetic CD data had shown that the
      mutant fractions contain P-clusters, and thus the mutated residues are not as
      essential for maintaining the integrity of the P-clusters as they appear from the
      X-ray structure. The specific activity of each of the three fractions was less
      than that of wild-type Kp1, the most active fraction having only 50% of wild-type
      activity. No change in substrate specificity or in the relative distribution of
      electrons to various substrates was found. The relationship between ATP
      hydrolysis and substrate-reducing activity, the EPR spectra of the S = 3/2 spin
      state of the iron-molybdenum cofactor (FeMoco) and the pH profile of acetylene
      reduction activities of the three fractions did not differ significantly from
      those exhibited by wild-type Kp1. The specific activities of the three mutant
      fractions and of wild-type Kp1 were linearly proportional to the intensity of the
      S = 3/2 EPR signal from the FeMoco centres. This implies that those molecules of
      the three mutant fractions and the wild-type protein that contain EPR-active
      FeMoco are fully active, i.e. that the Cys to Ala substitution of the P-cluster
      ligands does not affect the specific activity of the protein. This in turn
      implies that the P-clusters are not directly associated with the rate-limiting
      step in enzyme turnover. We conclude that the lower specific activities of the
      mutant fractions are observed because the fractions are mixtures of species
      containing a full complement of FeMoco and P-clusters and species lacking some or
      all of these clusters. On the basis of the Mo contents and EPR spectroscopy of
      the mutant fractions, we propose that the loss of the P-clusters causes (i) the
      physical loss or inhibition of binding of some FeMoco; (ii) the EPR and catalytic
      inactivation of some FeMoco; and/or (iii) the incorporation of a FeMoco-like
      species into the FeMoco site of the mutant molecules.

PMID- 8761460
TI  - Glycation and inactivation of sorbitol dehydrogenase in normal and diabetic rats.
AB  - Sorbitol dehydrogenase (SDH) is involved in the polyol pathway, which plays an
      important role in the pathogenesis of diabetic complications. We have measured
      the tissue distributions of SDH mRNA, both the immunoreactive enzyme levels and
      the enzyme activity. SDH mRNA was especially abundant in liver, kidney and
      testis. Both the activity and enzyme content are high in liver and kidney but not
      in testis. The discrepancy between mRNA and immunoreactive enzyme levels and the
      activity of SDH observed in testis was also seen in livers of streptozotocin
      induced diabetic rats. SDH was found to exist in both glycated and non-glycated
      forms, with larger amounts of the glycated protein in the diabetic liver.
      Moreover, after incubation of purified enzyme with glucose or fructose, its
      activity was markedly decreased. These results indicate that glycation causes a
      decrease in SDH activity in liver under diabetic conditions. The same post
      transcriptional event might occur to decrease the activity of SDH in testis in
      normal animals.

PMID- 8761462
TI  - Towards a classification of glycosyltransferases based on amino acid sequence
      similarities: prokaryotic alpha-mannosyltransferases.
AB  - A number of genes encoding bacterial glycosyltransferases have been sequenced
      during the last few years, but their low sequence similarity has prevented a
      straightforward grouping of these enzymes into families. The sequences of several
      bacterial alpha-mannosyltransferases have been compared using current alignment
      algorithms as well as hydrophobic cluster analysis (HCA). These sequences show a
      similarity which is significant but too low to be reliably aligned using
      automatic alignment methods. However, a region spanning approx. 270 residues in
      these proteins could be aligned by HCA, and several invariant amino acid residues
      were identified. These features were also found in several other
      glycosyltransferases, as well as in proteins of unknown function present in
      sequence databases. This similarity most probably reflects the existence of a
      family of proteins with conserved structural and mechanistic features. It is
      argued that the present IUBMB classification of glycosyltransferases could be
      complemented by a classification of these enzymes based on sequence similarities
      analogous to that which we proposed for glycosyl hydrolases [Henrissat, B. (1991)
      Biochem. J. 280, 309-316].

PMID- 8761461
TI  - Drosophila melanogaster angiotensin I-converting enzyme expressed in Pichia
      pastoris resembles the C domain of the mammalian homologue and does not require
      glycosylation for secretion and enzymic activity.
AB  - Drosophila melanogaster angiotensin I-converting enzyme (AnCE) is a secreted
      single-domain homologue of mammalian angiotensin I-converting enzyme (ACE) which
      comprises two domains (N and C domains). In order to characterize in detail the
      enzymic properties of AnCE and to study the influence of glycosylation on the
      secretion and enzymic activity of this enzyme, we overexpressed AnCE (expression
      level, 160 mg/l) and an unglycosylated mutant (expression level, 43 mg/l) in the
      yeast Pichia pastoris. The recombinant enzyme was apparently homogeneous on
      SDS/PAGE without purification and partial deglycosylation demonstrated that all
      three potential sites for N-linked glycosylation were occupied by oligosaccharide
      chains. Each N-glycosylation sequence (Asn-Xaa-Ser/Thr) was disrupted by
      substituting a glutamine for the asparagine residue at amino acid positions 53,
      196 and 311 by site-directed mutagenesis to produce a single mutant. Expression
      of the unglycosylated mutant in Pichia produced a secreted catalytically active
      enzyme (AnCE delta CHO). This mutant displayed unaltered kinetics for the
      hydrolyses of hippuryl-His-Leu, angiotensin 1 and N-acetyl-Ser-Asp-Lys-Pro
      (AcSDKP) and was equally sensitive to ACE inhibitors compared with wild-type
      AnCE. However, AnCE delta CHO was less stable, displaying a half-life of 4.94 h
      at 37 degrees C, compared with AnCE which retained full activity under the same
      conditions. Two catalytic criteria demonstrate the functional resemblance of AnCE
      with the human ACE C domain: first, the kcat/Km of AcSDKP hydrolysis and
      secondly, the kcat/Km and optimal chloride concentration for hippuryl-His-Leu
      hydrolysis. A range of ACE inhibitors were far less potent towards AnCE compared
      with the human ACE domains, except for captopril which suggests an alternative
      structure in AnCE corresponding to the region of the S1 subsite in the human ACE
      active sites.

PMID- 8761463
TI  - Lecithin hydrophobicity modulates the process of cholesterol crystal nucleation
      and growth in supersaturated model bile systems.
AB  - The present study was performed to determine whether the degree of lecithin
      hydrophobicity regulates bile metastability and, therefore, affects the process
      of cholesterol crystallization. Supersaturated model bile (MB) solutions were
      prepared with an identical composition on a molar basis
      (taurocholate/lecithin/cholesterol, 73:19.5:7.5; total lipid concentration 9
      g/dl) except for the lecithin species; egg yolk phosphatidylcholine, soybean
      phosphatidylcholine, 1-palmitoyl-2-linoleoyl-sn-phosphatidylcholine, dilinoleoyl
      phosphatidylcholine and dipalmitoyl phosphatidylcholine. Each MB solution was
      incubated and sequentially examined. Video-enhanced contrast microscopy
      demonstrated that the rate of vesicular aggregation and fusion correlated with
      the degree of lecithin hydrophobicity, and that the rate of cholesterol crystal
      nucleation correlated with the degree of lecithin hydrophilicity. In MBs
      containing less hydrophobic lecithin, needle-like crystals developed and
      transformed into mature plate-like crystals, whereas classical plate-like
      crystals were consistently observed in MBs composed of hydrophobic lecithin.
      Laser-diffraction particle size analysis demonstrated that the increase in
      lecithin hydrophobicity enlarged the vesicle dimension, enhancing its cholesterol
      holding capacity. Correlation between vesicular cholesterol packing density and
      lecithin hydrophobicity suggests that the process of bile cholesterol nucleation
      and growth is regulated, in part, by acyl chain unsaturation in lecithin. Since
      the composition of biliary lecithins is responsive to dietary manipulations, this
      study provides new insights into the prevention of cholesterol gallstones.

PMID- 8761464
TI  - Spectrophotometric titration with cobalt(III) for the determination of accurate
      absorption coefficients of transferrins.
AB  - A rapid and sensitive technique, involving difference spectral titration with
      cobalt(III), to measure the epsilon values of chicken ovotransferrin, human serum
      transferrin, the N-lobe of human transferrin and several single point mutants is
      reported. The resulting epsilon values were compared with the values calculated
      from the equation proposed by Pace, Vajdos, Fee, Grimsley and Gray [(1995)
      Protein Sci. 4, 2411-2423]. The titrations with cobalt feature sharp break-points
      and do not destroy the protein samples. The choice of buffer was found to be
      important, depending on the metal-binding avidity of the proteins. Cobalt
      titration should prove useful for studying the comparative metal-binding
      properties of transferrin and mutants of transferrin being generated by
      recombinant technology.

PMID- 8761465
TI  - Functional domains on elastin and microfibril-associated glycoprotein involved in
      elastic fibre assembly.
AB  - Studies in vitro suggest that the C-terminus of tropoelastin mediates elastin
      polymerization through an interaction with microfibril-associated proteins. In
      this study we have used cultured auricular chondrocytes as a model system to
      examine whether this interaction is critical for elastic fibre formation in vivo.
      Auricular chondrocytes, which deposit an abundant elastic fibre matrix, were
      cultured in the presence of Fab fragments of antibodies directed against the C
      terminus (CTe) or an N-terminal domain (ATe) of tropoelastin. Immunofluorescent
      staining of the extracellular matrix deposited by the cells showed that the CTe
      antibody inhibited the deposition of elastin without affecting microfibril
      structure. Cells grown under identical conditions in the presence of ATe,
      however, formed fibres that stained normally for both elastin and microfibril
      proteins. Chondrocytes cultured in the presence of microfibril-associated
      glycoprotein (MAGP):21-35, an antibody directed against a domain near the N
      terminus of MAGP, did not organize tropoelastin into fibres. However,
      immunostaining for MAGP and fibrillin revealed normal microfibrils. In agreement
      with the immunofluorescence staining patterns, fewer elastin-specific cross
      links, indicative of insoluble elastin, were detected in the extracellular matrix
      of cells cultured in the presence of CTe. The medium from these cultures,
      however, contained more soluble elastin, consistent with an antibody-induced
      alteration of elastin assembly but not its synthesis. Northern analysis of
      antibody-treated and control cultures substantiated equivalent levels of
      tropoelastin mRNA. These results confirm that the C-terminus of tropoelastin
      interacts with microfibrils during the assembly of elastic fibres. Further, the
      results suggest that the interaction between tropoelastin and microfibrils might
      be mediated by a domain involving the N-terminal half of MAGP.

PMID- 8761466
TI  - Molecular cloning and overexpression of a glutathione transferase gene from
      Proteus mirabilis.
AB  - The structural gene of the Proteus mirabilis glutathione transferase GSTB1-1
      (gstB) has been isolated from genomic DNA. A nucleotide sequence determination of
      gstB predicted a translational product of 203 amino acid residues, perfectly
      matching the sequence of the previously purified protein [Mignogna, Allocati,
      Aceto, Piccolomini, Di Ilio, Barra and Martini (1993) Eur. J. Biochem. 211, 421
      425]. The P. mirabilis GST sequence revealed 56% identity with the Escherichia
      coli GST at DNA level and 54% amino acid identity. Similarity has been revealed
      also with the translation products of the recently cloned gene bphH from
      Haemophilus influenzae (28% identity) and ORF3 of Burkholderia cepacia (27%
      identity). Putative promoter sequences with high similarity to the E. coli sigma
      70 consensus promoter and to promoters of P. mirabilis cat and glnA genes
      preceded the ATG of the gstB open reading frame (ORF). gstB was brought under
      control of the tac promoter and overexpressed in E. coli by induction with
      isopropyl-beta-D-thiogalactopyranoside and growth at 37 degrees C. The
      physicochemical and catalytic properties of overexpressed protein were
      indistinguishable from those of the enzyme purified from P. mirabilis extract.
      Unlike the GST belonging to Mu and Theta classes, GSTB1-1 was unable to
      metabolize dichloromethane. The study of the interaction of cloned GSTB1-1 with a
      number of antibiotics indicates that this enzyme actively participates in the
      binding of tetracyclines and rifamycin.

PMID- 8761468
TI  - Down-regulation of hormone-sensitive lipase in sterol ester-laden J774.2
      macrophages.
AB  - The development of atherosclerotic plaques in arteries is a key step in
      atherogenesis, with cholesterol ester accumulation in macrophage-derived foam
      cells being recognized as a major pathogenic event in this process. In this
      study, the mouse macrophage cell line J774.2 was induced to accumulate
      intracellular sterol esters by incubation with 25-hydroxycholesterol in the
      presence of oleic acid. The accumulation of sterol esters in these cells was
      found to be accompanied by a marked decrease in the activity of the enzyme
      responsible for their hydrolysis, namely hormone-sensitive lipase (HSL); Western
      blotting studies revealed a corresponding decrease in the levels of the HSL
      polypeptide. Similar findings were obtained after incubation with oxidized low
      density lipoprotein or very-low-density lipoprotein. These findings suggest that
      down-regulation of the expression of HSL is important in cholesterol ester
      accumulation in macrophages.

PMID- 8761467
TI  - Cytoplasmic tail length influences fatty acid selection for acylation of viral
      glycoproteins.
AB  - We report remarkable differences in the fatty acid content of thioester-type
      acylated glycoproteins of enveloped viruses from mammalian cells. The E2
      glycoprotein of Semliki Forest virus contains mainly palmitic acid like most
      other palmitoylated proteins analysed so far. However, the other glycoprotein
      (E1) of the same virus, as well as the HEF (haemagglutinin esterase fusion)
      glycoprotein of influenza C virus, are unique in this respect because they are
      acylated primarily with stearic acid. Comparative radiolabelling of uninfected
      cells with different fatty acids suggests that stearate may also be the
      prevailing fatty acid in some cellular acylproteins. To look for further
      differences between palmitoylated and stearoylated glycoproteins we characterized
      stearoylation in more detail. We identified the acylation site of HEF as a
      cysteine residue located at the boundary between the transmembrane region and the
      cytoplasmic tail. The attachment of stearate to HEF and E1 occurs post
      translationally in a pre-Golgi compartment. Thus, stearoylated and palmitoylated
      proteins cannot be discriminated on the basis of the fatty acid linkage site or
      the intracellular compartment, where acylation occurs. However, stearoylated
      acylproteins contain a very short, positively charged cytoplasmic tail, whereas
      in palmitoylated proteins this molecular region is longer. Replacing the short
      cytoplasmic tail of stearoylated HEF with the long influenza A virus
      haemagglutinin (HA) tail in an HEF-HA chimera, and subsequent vaccinia T7
      expression in CV-1 cells, yielded proteins with largely palmitic acid bound. The
      reverse chimera, HA-HEF with a short cytoplasmic tail was not fatty acylated at
      all during expression, indicating that conformational or topological constraints
      control fatty acid transfer.

PMID- 8761469
TI  - Involvement of an arginyl residue in the nucleotide-binding site of Ca(2+)-ATPase
      from sarcoplasmic reticulum as seen by reaction with phenylglyoxal.
AB  - 1. Chemical modification of the Ca(2+)-ATPase with phenylglyoxal, as a modifier
      of arginine residues, leads to an almost total loss of the ATPase activity. The
      presence of nucleotides in the reaction medium protects against the binding of 18
      nmol of phenylglyoxal/mg of protein and this reduction in the binding of
      phenylglyoxal is accompanied by a substantial retention of ATPase activity. The
      incorporation of phenylglyoxal to the protein alters neither calcium binding nor
      phosphorylation from inorganic phosphate. Nevertheless the binding of nucleotides
      is dramatically inhibited and, consequently, so is phosphorylation from ATP.
      Fluorescein 5'-isothiocyanate labelling of the phenylglyoxal-modified ATPase is
      not affected but, on the other hand, phenylglyoxal is not able to modify the
      fluorescein 5'-isothiocyanate-prelabelled ATPase. The way in which ATPase
      inhibition depends on the presence of phenylglyoxal indicates that this process
      occurs in a pseudo-first-order reaction. However, the dependence of the apparent
      first-order rate constant on phenylglyoxal concentration appears to be more
      complex and an inhibition mechanism of two steps, with phenylglyoxal binding, has
      to be taken into account. 2. We have found that phenylglyoxal labels both A and B
      tryptic fragments, but only B fragment labelling is prevented by ATP. The
      sequencing of peptides from mild acid hydrolysis of phenylglyoxal-labelled ATPase
      shows that phenylglyoxal is located in the Ala506-Gly595 peptide that is a part
      of the B fragment. 3. We conclude that phenylglyoxal inactivates the calcium pump
      in a two-step mechanism in which the second step is irreversible. Phenylglyoxal
      labels an arginyl residue in the Ala506-Gly595 peptide that can be protected by
      the binding of ATP to its site.

PMID- 8761470
TI  - Dual regulation of heat-shock transcription factor (HSF) activation and DNA
      binding activity by H2O2: role of thioredoxin.
AB  - The heat-shock (HS) response is a ubiquitous cellular response to stress,
      involving the transcriptional activation of HS genes. Reactive oxygen species
      (ROS) have been shown to regulate the activity of a number of transcription
      factors. We investigated the redox regulation of the stress response and report
      here that in the human pre-monocytic line U937 cells, H2O2 induced a
      concentration-dependent transactivation and DNA-binding activity of heat-shock
      factor-1 (HSF-1). DNA-binding activity was, however, lower with H2O2 than with
      HS. We thus hypothesized a dual regulation of HSF by oxidants. We found that
      oxidizing agents, such as H2O2 and diamide, as well as alkylating agents, such as
      iodoacetic acid, abolished, in vitro, the HSF-DNA-binding activity induced by HS
      in vivo. The effects of H2O2 in vitro were reversed by the sulphydryl reducing
      agent dithiothreitol and the endogenous reductor thioredoxin (TRX), while the
      effects of iodoacetic acid were irreversible. In addition, TRX also restored the
      DNA-binding activity of HSF oxidized in vivo, while it was found to be itself
      induced in vivo by both HS and H2O2. Thus, H2O2 exerts dual effects on the
      activation and the DNA-binding activity of HSF: on the one hand, H2O2 favours the
      nuclear translocation of HSF, while on the other, it alters HSF-DNA-binding
      activity, most likely by oxidizing critical cysteine residues within the DNA
      binding domain. HSF thus belongs to the group of ROS-modulated transcription
      factors. We propose that the time required for TRX induction, which may restore
      the DNA-binding activity of oxidized HSF, provides an explanation for the delay
      in heat-shock protein synthesis upon exposure of cells to ROS.

PMID- 8761471
TI  - Growth-condition-dependent regulation of insulin-like growth factor II mRNA
      stability.
AB  - Insulin-like growth factor II (IGF-II) is synthesized in many tissues, but the
      main site of production is the liver. In this paper we show that IGF-II mRNA
      levels are dependent on the growth conditions of the cells. In Hep3B cells, serum
      deprivation leads to a marked increase in IGF-II mRNA levels. Serum stimulation
      of starved Hep3B cells induces a decrease in the amount of IGF-II mRNA, which is
      not caused by a change in promoter activity. IGF-II mRNAs are subject to
      endonucleolytic cleavage, a process that requires two widely separated elements
      in the 3' untranslated region of the mRNA. Specific regions of these elements can
      form a stable stem structure which is involved in the formation of RNA-protein
      complexes. By employing electrophoretic mobility shift assays, two complexes have
      been identified in cytoplasmic extracts of Hep3B cells. The formation of these
      complexes is related to the growth conditions of the cells and is correlated with
      the regulation of IGF-II mRNA levels. Our data suggest that, depending on whether
      serum is present or absent, a transition from one complex to the other occurs. A
      decrease in the IGF-II mRNA level is also observed when IGF-I or IGF-II is added
      to serum-deprived Hep3B cells, possibly providing a feedback mechanism for IGF-II
      production. The serum-induced degradation of IGF-II mRNAs does not require de
      novo protein synthesis, and is abolished by rapamycin, an inhibitor of p70 S6
      kinase.

PMID- 8761472
TI  - Phorbol esters stimulate phosphatidylinositol 3,4,5-trisphosphate production in
      3T3-L1 adipocytes: implications for stimulation of glucose transport.
AB  - The effects of insulin and phorbol 12-myristate 13-acetate (PMA) on the levels of
      cellular phosphoinositides were investigated in 3T3-L1 adipocytes. Stimulation
      for 4 min with PMA (1 microM) or insulin (10 nM) increased levels of
      PtdIns(3,4,5)P3 approx. 2-fold and 6-fold respectively. PMA also had a small
      effect on the cellular levels of PtdIns4P, whereas insulin had no effect on
      PtdIns4P levels; levels of PtdIns(4,5)P2 and PtdIns3P were not significantly
      affected by either agent. Insulin increased the levels of the p85 alpha subunit
      of phosphoinositide (PI) 3-kinase associated with membranes, whereas PMA
      decreased levels of membrane-associated p85 alpha. PMA did not increase PI 3
      kinase activity in anti-phosphotyrosine or anti-p85 immunoprecipitates. The
      stimulation of glucose transport by insulin or PMA was blocked by 100 nM
      wortmannin or 10 ng/ml LY294002, indicating that PI 3-kinase is essential for
      stimulation by both agents. In summary, these results demonstrate: (1) that PMA
      and insulin stimulate PtdIns(3,4,5)P3 production by distinct mechanisms in 3T3-L1
      adipocytes, and (2) that stimulation of PtdIns(3,4,5)P3 production by PMA is
      likely to be important in signalling pathways leading from PMA stimulation to end
      point responses such as glucose transport.

PMID- 8761474
TI  - Human rhinovirus 2A proteinase mutant and its second-site revertants.
AB  - The 2A proteinases of human rhinoviruses are cysteine proteinases with marked
      similarities to serine proteinases. In the absence of a three-dimensional
      structure, we developed a genetical screening system for proteolytic activity and
      identified Phe-130 as a key residue. The mutation Phe-130-->Tyr almost completely
      inhibited enzyme activity at 37 degrees C; activity was, however, partially
      restored by the following exchanges: Ser-27-->Pro, His-135-->Arg or His-137-
      >Arg. To investigate this phenotypic reversion, 2A proteinases with the mutations
      Phe-130-->Tyr, Phe-130-->Tyr/His-135-->Arg, Phe-130-->Tyr/His-137-->Arg, His-135-
      >Arg or His-137-->Arg were expressed in Escherichia coli and purified. None of
      these mutations affected the affinity of the enzyme for a peptide substrate.
      However, the temperature-dependence of enzyme activity, as assayed by cleavage of
      a peptide substrate and by monitoring the toxicity of the proteinases towards the
      E. coli strain BL21(DE3), and the structural stability, as monitored by 8-anilino
      I-naphthalenesulphonic acid fluorescence and CD spectrometry, were affected. The
      thermal transition temperatures for both the activity and the stability of the
      Phe-130-->Tyr 2A proteinase were reduced by about 17 degrees C compared with the
      wild-type enzyme. The presence of the additional mutations His-135-->Arg or His
      137-->Arg in the Phe-130-->Tyr mutant increased temperature stability by 3
      degrees C and 6 degrees C respectively. Thus essential interactions exist within
      the C-terminal domain of human rhinoviral 2A proteinases which contribute to the
      overall stability and integrity of the enzyme.

PMID- 8761473
TI  - Inhibition of mitogen-activated protein kinase kinase does not impair primary
      activation of human platelets.
AB  - Mitogen-activated protein kinases (MAPKs), a family of protein serine/threonine
      kinases regulating cell growth and differentiation, are activated by a dual
      specificity kinase through phosphorylation at threonine and tyrosine. We used a
      recently described selective inhibitor of the p42/p44mapk-activating enzyme, PD
      98059 [2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one], to investigate the
      role of the p42/p44mapk pathway in human platelets. PD 98059 inhibited
      p42/p44mapk activation in thrombin-, collagen- and phorbol esterstimulated
      platelets, as determined from in-gel renaturation kinase assays, with an IC50 of
      approx. 5 microM (thrombin stimulation). It also prevented activation of MAPK
      kinase, which was measured in whole-cell lysates with glutathione S
      transferase/p42mapk fusion protein (GST-MAPK) as substrate. Inhibition of
      p42/p44mapk did not affect platelet responses to thrombin or collagen such as
      aggregation, 5-hydroxytryptamine release and protein kinase C activation. In
      addition, PD 98059 did not interfere with release of arachidonic acid, a response
      mediated by cytosolic phospholipase A2 (cPLA2), or with cPLA2 phosphorylation.
      This suggests that platelet cPLA2 is not regulated by p42/p44mapk after
      stimulation with physiological agonists. In contrast, phorbol ester-induced
      phosphorylation of cPLA2 and potentiation of arachidonic acid release stimulated
      by Ca2+ ionophore A23187 were inhibited by PD 98059, indicating that p42/p44mapk
      phosphorylates cPLA2 after activation of protein kinase C by the non
      physiological tumour promoter.

PMID- 8761475
TI  - Identification of a vitamin D3-response element that overlaps a unique inverted
      TATA box in the rat bone sialoprotein gene.
AB  - Bone sialoprotein (BSP), an early marker of osteoblast differentiation, has been
      implicated in the nucleation of hydroxyapatite during bone formation de novo. Our
      studies, using the osteoblastic cell line ROS 17/2.8, have revealed that rat BSP
      gene expression is suppressed by 1,25-dihydroxyvitamin D3[1,25(OH)2D3], which is
      a powerful regulator of bone formation and resorption. To determine the molecular
      basis of the transcriptional suppression of BSP gene transcription by
      1,25(OH)2D3, we have conducted transient transfection analyses with chimaeric
      constructs of the rat BSP gene promoter linked to a luciferase reporter gene.
      1,25(OH)2D3 suppressed expression in all constructs, including a short construct
      (pLUC 3; nt -116 to +60) that contained a putative vitamin D3-response element
      (VDRE; AGGGTTTATAGGTCA; nt -28 to -14) that overlaps a unique inverted TATA
      (TTTATA) box. Mobility shift assays demonstrated strong binding of recombinant
      human vitamin D3 receptor protein (hVDR) to the VDRE. Point mutations introduced
      into each half-site and analysed for 1,25(OH)2D3-mediated suppression of
      transcription and for hVDR binding either decreased or increased both
      transcriptional suppression and binding. In comparison with activating VDREs, the
      rat BSP VDRE bound VDR-VDR homodimers more avidly than VDR-RXR alpha heterodimers
      (where RXR is retinoid X receptor). These studies have therefore identified a
      novel 1,25(OH)2D3 suppressor element that overlaps the inverted TATA box in the
      rat BSP gene and indicate that transcriptional suppression of the rat BSP gene by
      1,25(OH)2D3 might involve competition between the VDR and the TATA binding
      protein (TBP).

PMID- 8761476
TI  - Covalent dimerization of ribulose bisphosphate carboxylase subunits by UV
      radiation.
AB  - The effect of UV radiation (UV-A, UV-B and UV-C) on ribulose bisphosphate
      carboxylase from a variety of plant species was examined. The exposition of plant
      leaves or the pure enzyme to UV radiation produced a UV-dependent accumulation of
      a +5 kDa polypeptide (P65). Different approaches were utilized to elucidate the
      origin and structure of P65: electrophoretic and fluorographic analyses of 35S
      labelled ribulose bisphosphate carboxylase exposed to UV radiation and
      immunological experiments using antibodies specific for P65, for the large and
      small subunits of ribulose bisphosphate carboxylase and for high-molecular-mass
      aggregates of the enzyme. These studies revealed that P65 is a dimer, formed by
      the covalent, non-disulphide linkage of one small subunit with one large subunit
      of ribulose bisphosphate carboxylase. For short periods of time (< 1 h), the
      amount of P65 formed increased with the duration of the exposure to the UV
      radiation and with the energy of the radiation applied. Prolonged exposure to UV
      radiation (1-6 h) resulted in the formation of high-molecular-mass aggregates of
      ribulose bisphosphate carboxylase. Formation of P65 was shown to depend on the
      native state of the protein, was stimulated by inhibitors of enzyme activity, and
      was inhibited by activators of enzyme activity. A UV-independent accumulation of
      P65 was also achieved by the in vitro incubation of plant crude extracts.
      However, the UV-dependent and the UV-independent formation of P65 seemed to occur
      by distinct molecular mechanisms. The UV-dependent accumulation of P65 was
      immunologically detected in all species examined, including Lemna minor, Arum
      italicum, Brassica oleracea, Triticum aestivum, Zea mays, Pisum sativum and
      Phaseolus vulgaris, suggesting that it may constitute a universal response to UV
      radiation, common to all photo-synthetic tissues.

PMID- 8761477
TI  - Acetate represents a major product of heptanoate and octanoate beta-oxidation in
      hepatocytes isolated from neonatal piglets.
AB  - An experiment was conducted to explore the nature of the radiolabel distribution
      in acid-soluble products (ASPs) resulting from the oxidation of [1-14C]C7:0 or
      C8:0 by isolated piglet hepatocytes. The differences between odd and even chain
      length and the impacts of valproate and malonate upon the rate of beta-oxidation
      and ASP characteristics were tested. A minor amount of fatty acid carboxyl carbon
      (< or = 10% of organic acids identified by radio-HPLC) accumulated in ketone
      bodies regardless of chain-length or inhibitor used. In all cases, acetate
      represented the major reservoir of carboxyl carbon, accounting for 60-70% of
      radiolabel in identified organic acids. Cells given [1-14C]C7:0 accumulated 85%
      more carboxyl carbon in Krebs cycle intermediates when compared with C8:0, while
      accumulation in acetate was unaffected. The results are consistent with the
      hypothesis that anaplerosis from odd-carbon fatty acids affects the oxidative
      fate of fatty acid carbon. The piglet appears unique in that non-ketogenic routes
      of fatty acid carbon flow (i.e. acetogenesis) predominate in the liver of this
      species.

PMID- 8761479
TI  - Tyrosine phosphorylation and activation of a new mitogen-activated protein (MAP)
      kinase cascade in human neutrophils stimulated with various agonists.
AB  - The presence of a novel 38 kDa protein that is tyrosine phosphorylated in human
      neutrophils, a terminally differentiated cell, upon stimulation of these cells
      with low concentrations of lipopolysaccharide (LPS) in combination with serum has
      been demonstrated. This 38 kDa protein was identified as the mammalian homologue
      of HOG1 in yeast, the p38 mitogen-activated protein (MAP) kinase. This conclusion
      is based on the experimental findings that anti-phosphotyrosine (anti-PY)
      antibody immunoprecipitates a 38 kDa protein that is recognized by anti-p38 MAP
      kinase antibody, and conversely, anti-p38 MAP kinase antibody immunoprecipitates
      a 38 kDa protein that can be recognized by anti-PY antibody. Moreover, this
      tyrosine phosphorylated protein is found associated entirely with the cytosol. It
      was also found that this p38 MAP kinase is activated following stimulation of
      these cells with low concentrations of LPS in combination with serum. This
      conclusion is based on three experimental findings. First, soluble fractions
      isolated from LPS-stimulated cells phosphorylate heat shock protein 27 (hsp27) in
      an in vitro assay, and this effect is not inhibited by protein kinase C and
      protein kinase A inhibitor peptides. This effect is similar to the effect
      produced by the commercially available phosphorylated and activated MAPKAP kinase
      2 (MAP kinase activated protein kinase-2). Secondly, a 27 kDa protein that aligns
      with a protein recognized by anti-hsp27 antibody is phosphorylated upon LPS
      stimulation of intact human neutrophils prelabelled with radioactive phosphate.
      Lastly, immune complex protein kinase assays, using [gamma-32P]ATP and activating
      transcription factor 2 (ATF2) as substrates, showed increased p38 MAP kinase
      activity from LPS-stimulated human neutrophils. The phosphorylation and
      activation of this p38 MAP kinase can be affected by both G-protein-coupled
      receptors such as platelet-activating factor (PAF) and non-G-protein-coupled
      receptors such as the cytokine-coupled receptors for granulocyte-macrophage
      colony-stimulating factor (GM-CSF) and tumour necrosis factor alpha (TNF-alpha).
      The effect of low concentrations of PAF is greatly increased in cells pretreated
      with LPS. The tyrosine phosphorylation of the p38 MAP kinase is not restricted to
      stimuli that mediate their actions through membrane-associated receptors, but it
      can be affected by agents that bypass membrane-associated receptors such as the
      protein translation blocker anisomycin. While anisomycin is known to increase the
      tyrosine phosphorylation of the 54 kDa SAPK (stress-activated protein kinase),
      this is the first report that shows that anisomycin also tyrosine phosphorylates
      the p38 MAP kinase. Cytokine receptors that increase the tyrosine phosphorylation
      and activation of the erk1 and erk2 MAP kinases have less effect on this p38 MAP
      kinase than those that do not affect the erk1 and erk2 MAP kinases. The possible
      role of the p38 MAP kinase in the phosphorylation of cytosolic phospholipase A2
      is discussed.

PMID- 8761478
TI  - A rat skeletal muscle cell line (L6) expresses specific adrenomedullin binding
      sites but activates adenylate cyclase via calcitonin gene-related peptide
      receptors.
AB  - We have previously demonstrated specific binding sites for adrenomedullin, a
      novel member of the calcitonin family of peptides, in rat muscles. It is unclear
      whether these receptors are vascular or muscular. Receptors for the structurally
      similar calcitonin gene-related peptide (CGRP) are present on myocytes and might
      be involved in the regulation of myocyte glucose metabolism and control by motor
      neurons. We investigated whether adrenomedullin binding sites were present on L6
      myocytes. Specific [125I]adrenomedullin binding sites were demonstrated where
      adrenomedullin competed with an IC50 of 0.22 +/- 0.04 nM (mean +/- S.E.M.) and a
      concentration of binding sites (Bmax) of 0.95 +/- 0.19 pmol/mg of protein (mean
      +/- S.E.M.). CGRP and the specific CGRP receptor antagonist CGRP(8-37) competed
      weakly at this site (IC50 > 10 and 601 +/- 298 nM respectively). Binding studies
      with [125I]CGRP revealed a binding site for CGRP (IC50 = 0.13 +/- 0.01 nM; Bmax =
      0.83 +/- 0.10 pmol/mg of protein) where both CGRP(8-37) and adrenomedullin
      competed with [125I]CGRP with IC50 values of 1.15 +/- 0.12 and 8.68 +/- 0.98 nM
      respectively. Chemical cross-linking showed the CGRP and adrenomedullin binding
      site-ligand complexes to have approximate molecular masses of 82 and 76 kDa
      respectively. Both CGRP and adrenomedullin increased adenylate cyclase activity
      with similar potencies. In both cases adenylate cyclase activation was blocked by
      CGRP(8-37). Stimulation with 10 nM adrenomedullin or CGRP caused an increase in
      the percentage of total activated cellular cAMP-dependent protein kinase from 38%
      in resting cells to 100% and 98% respectively. Therefore in L6 cells
      adrenomedullin can bind to CGRP receptors, activating adenylate cyclase and cAMP
      dependent protein kinase.

PMID- 8761480
TI  - The SH3 domain of Src tyrosyl protein kinase interacts with the N-terminal splice
      region of the PDE4A cAMP-specific phosphodiesterase RPDE-6 (RNPDE4A5).
AB  - The PDE4A (type IV) cAMP-specific, rolipram-inhibited phosphodiesterase RPDE-6
      (RNPDE4A5), when transiently expressed in COS7 cells, could be complexed with the
      v-Src-SH3 domain expressed as a glutathione S-transferase (GST) fusion protein.
      RPDE-6 did not interact with GST itself. This complex was not disrupted by
      treatment with high NaCl concentration together with Triton X-100. Interaction
      was apparently determined by the N-terminal splice region of RPDE-6, as the PDE4A
      splice variant RPDE-39, which differs from RPDE-6 at the extreme N-terminus,
      failed to associate with v-Src-SH3; met26RD1 (where RD1 is rat 'dunc-like' PDE),
      which has the N-terminal splice region deleted, failed to associate with v-Src
      SH3, and the association of RPDE-6 and v-Src-SH3 was blocked by a fusion protein
      formed from the N-terminal splice region. RDPE-6 showed binding to GST fusion
      proteins of both the intact Src kinase and an SH2-SH3 construct but did not bind
      to the Src-SH2 domain or to the adaptor protein Grb-2. RPDE-6 could be co
      immunoprecipitated from cytosol extracts of transfected cells by using anti-Src
      antiserum. RPDE-6 exhibited selectivity in binding to the SH3 domains of c-Abl,
      Crk, Csk, Lck, Lyn, Fyn and v-Src, with binding to the SH3 regions of the Src
      related tyrosyl kinases Lyn and Fyn being the most effective. The binding of RPDE
      6 to the SH3 domains of Crk, Csk and Lck led to a marked reduction in PDE
      activity, but no change was apparent in complexes with other species. Endogenous
      RPDE-6 from brain, but not endogenous RPDE-39 from testis, bound to the Src-SH3
      domain. We suggest that the PDE4A splice variant RPDE-6 has a propensity for
      interaction with selective SH3 domains, in particular those from Src and the Src
      related tyrosyl kinases Lyn and Fyn. This interaction seems to be governed by
      alternative splicing of the PDE4A gene, because RPDE-39, a splice variant that
      lacks the proline-rich N-terminal splice region of RPDE-6, does not interact with
      these SH3 domains. It is proposed that the binding site on RPDE-6 for SH3 domains
      lies within the unique first 102 residues of its N-terminal splice domain, where
      two motifs representing Class I SH3 binding sites with selectivity for Src kinase
      SH3 domains can be identified and one motif for a putative Class II SH3 binding
      site.

PMID- 8761481
TI  - Ligand-dependent enhancement of human antithrombin gene expression by retinoid X
      receptor alpha and thyroid hormone receptor beta.
AB  - We studied potential modulators of antithrombin gene expression. A putative
      hormone response element (HRE) was identified by sequence similarity analysis of
      the antithrombin promoter, situated between nucleotides -92 and -54 relative to
      the transcription start site. This HRE contains three hexa-nucleotide motifs with
      an AGGTCA consensus, which are potential targets of members of the
      steroid/thyroid superfamily of nuclear receptors. Stimulation of the hepatoma
      cell line HepG2 with the receptor ligands L-3,5,3'-tri-iodothyronine, all-trans
      retinoic acid, or their combination, increased production of antithrombin into
      the culture medium by 1.3-, 1.6-, and 2.0-fold, respectively. In contrast, the
      receptor ligand 1,25-dihydroxy-cholecalciferol[1,25-(OH)2VitD3] did not influence
      antithrombin production. Analysis of promoter chloramphenicol acetyl-transferase
      (CAT) constructs, showed that the first 86 bp of the antithrombin promoter region
      are sufficient for basal transcription. The DNA length polymorphism of 32 bp or
      108 bp, located upstream of position -276, did not influence anti-thrombin
      promoter activity. The antithrombin promoter activity dropped to background
      values when deleting the region -97/-49 of promoter fragment -453/+57.
      Transactivation of the antithrombin promoter by retinoid X receptor alpha (RXR
      alpha) (5-7-fold) or thyroid hormone receptor beta (TR beta) (4-5-fold) was only
      observed when at least -167/+57 bp of the promoter region is present in CAT
      constructs, and when the appropriate ligand of the nuclear receptor was added.
      This transactivation was not observed upon deletion of the antithrombin promoter
      region -97/-49. With three copies of the antithrombin promoter fragment -109/-42
      in front of the thymidine kinase minimal promoter, transactivation was only
      obtained with RXR alpha, and not with TR beta. In conclusion, these results
      indicate that the ligand-dependent enhancement of antithrombin gene expression is
      regulated by RXR alpha as well as by TR beta. Transactivation of antithrombin
      gene expression by RXR alpha and TR beta appears to be dependent upon the
      presence of promoter region up to nucleotide -167. The HRE segment (-109/-42)
      only confers RXR alpha responsiveness to a heterologous promoter. Further study
      is needed to unravel the exact nature of this HRE and its 5'-flanking sequences.

PMID- 8761483
TI  - Inositol phosphates in barley (Hordeum vulgare L.) aleurone tissue are
      stereochemically similar to the products of breakdown of InsP6 in vitro by wheat
      bran phytase.
AB  - Partisphere SAX HPLC analysis of endogenous inositol phosphates in [3H]inositol
      labelled barley aleurone tissue revealed a range of isomers, including D- and/or
      L-Ins3P, D- and/or L-Ins(1,4)P2, D- and/or L-Ins(1,2)P2, a third unidentified
      InsP2, Ins(1,2,3)P3, D- and/or L-Ins(1,2,6)P3, D-and/or L-Ins(1,2,3,4)P4, D-
      and/or L-Ins(1,2,5,6)P4, Ins(1,3,4,5,6)P5, D- and/or L-Ins(1,2,3,4,5)P5,
      Ins(1,2,3,4,6)P5, InsP6 and a molecule with the chromatographic properties of an
      inositol pyrophosphate. The striking match between the identities of the
      stereoisomers, and in some cases enantiomers, detected in vivo and those
      stereoisomers produced in vitro by the action of wheat-bran phytase on InsP6
      [Cosgrove (1980) Inositol Phosphates: Their Chemistry, Bio-chemistry and
      Physiology. Elsevier, Amsterdam] strongly suggests that most of the inositol
      phosphates identified are products of the breakdown of InsP4 by endogenous
      phytase(s) with stereospecificity similar to that of the wheat-bran enzyme(s).

PMID- 8761484
TI  - The activity on double-stranded RNA of aggregates of ribonuclease A higher than
      dimers increases as a function of the size of the aggregates.
AB  - Stable bovine RNase A aggregates larger than dimers (identified as trimers,
      tetramers, pentamers and hexamers) were obtained by lyophilization of RNase A
      from 40-50% acetic acid solutions. The RNase activity of these aggregates was
      compared with that of monomeric RNase A on single- and double-stranded
      polyribonucleotides. Their activity toward poly(U) and yeast RNA slightly
      decreases as a function of the size of the aggregates. In contrast, their action
      on poly(A).poly(U) as substrate progressively increases from a relative activity
      of 1 for the RNase monomer to 10 for the hexamer. These results are discussed in
      the light of an already advanced hypothesis about a possible mechanism of RNase
      attack on double-stranded RNA.

PMID- 8761482
TI  - Methylamine decreases trafficking and packaging of newly synthesized
      phosphatidylcholine in lamellar bodies in alveolar type II cells.
AB  - Lung lamellar bodies, the storage organelles for lung surfactant
      phosphatidylcholine (PC), maintain an acidic pH that can be increased with weak
      bases. This study investigates the effect of a weak base, methylamine, on the pH
      in lamellar bodies and on the trafficking and packaging of newly synthesized PC
      in lamellar bodies. Methylamine increased the pH of isolated lung lamellar bodies
      and of lamellar bodies in intact cells. Metabolic labelling of isolated type II
      cells with [methyl-3H]choline showed that although methylamine (2.5-10 mM) did
      not alter the labelling of cellular or microsomal PC and disaturated PC, it
      decreased the labelling of the PC and disaturated PC in lamellar bodies. The
      packaging of PC in lamellar bodies (the specific activities ratio between the PC
      in lamellar bodies and the microsomal PC) also decreased in a time- and
      concentration-dependent manner. The cellular synthesis of PC or its packaging
      into lamellar bodies was unaltered by brefeldin A, suggesting that the Golgi was
      not involved in PC packaging. Although methylamine also increased surfactant
      secretion, the inhibition of PC packaging in lamellar bodies seems unrelated to
      the secretagogue effect, (1) on the basis of metabolic consequences of increased
      secretion and (2) because ATP, another secretagogue, did not inhibit PC
      packaging. Methylamine seems to inhibit PC packaging by inhibiting trafficking of
      PC to lipid-rich light subcellular fractions. Together our results suggest that
      the trafficking of surfactant PC into lamellar bodies might be sensitive to
      changes in the pH of lamellar bodies.

PMID- 8761485
TI  - The distribution of theta-class glutathione S-transferases in the liver and lung
      of mouse, rat and human.
AB  - Two murine Theta-class glutathione S-transferases (GSTs), mGSTT1 and mGSTT2, have
      been cloned and sequenced. The murine cDNAs, together with the published
      sequences of the rat and human enzymes, were used to design oligonucleotide
      probes in order to determine the distribution of mRNA for these enzymes in the
      liver and lung of rat, mouse and human. The mRNA distribution was compared with
      that of enzyme protein determined with an antibody to rat GSTT2-2. Both the
      antibody and the oligonucleotide probes gave the same distribution patterns. Both
      enzymes were present at significantly higher concentrations in mouse tissues than
      in rat or human tissues. In mouse liver, both enzymes were localized in specific
      cell types and in nuclei. Although the distribution of GSTT2-2 in rat liver was
      similar to that seen in the mouse, GSTT1-1 was not localized in a specific cell
      type or in the nuclei of either rat or human liver. In the lungs, very high
      concentrations of the Theta enzymes were present in mouse-lung Clara cells and
      ciliated cells, with much lower levels in the Clara cells only of rat lung. Low
      levels of human transferase GSTT1-1 were detected in a small number of Clara
      cells and ciliated cells at the alveolar/ bronchiolar junction. The relative
      activities between species, and the cellular and sub-cellular distribution within
      the liver and lungs of each species, provides an explanation for the species
      specificity of methylene chloride, a mouse-specific carcinogen activated by
      glutathione S-transferase GSTT1-1.

PMID- 8761486
TI  - Regulation of 15-lipoxygenase expression in lung epithelial cells by interleukin
      4.
AB  - We have studied the expression of the 15-lipoxygenase gene in various permanent
      mammalian cell lines in response to interleukins-4 and -13, and found that none
      of the cell lines tested expressed 5-, 12- or 15-lipoxygenase when cultured under
      standard conditions. However, when the lung carcinoma cell line A549 was
      maintained in the presence of either interleukin for 24 h or more, we observed a
      major induction of 15-lipoxygenase, as indicated by quantification of 15
      lipoxygenase mRNA, by immunohistochemistry, by immunoblot analysis and by enzyme
      activity assays. This effect was 15-lipoxygenases-specific, since expression of 5
      and 12-lipoxygenases remained undetectable. The time course of interleukin-4
      treatment indicated maximal accumulation of both 15-lipoxygenase mRNA and
      functional protein after 48 h. Binding studies revealed that A549 cells express
      about 2100 high-affinity interleukin-4 binding sites per cell. The interleukin-4
      mutant Y124D, which is capable of binding to the interleukin-4 receptor but is
      unable to trigger receptor activation, counteracted the effect of the wild-type
      cytokine. Other cell lines, including several epithelial cells and various
      monocytic cell lines expressing comparable numbers of interleukin-4 receptors,
      did not express 15-lipoxygenase when stimulated with interleukin-4. These data
      indicate that A549 cells selectively express 15-lipoxygenase when stimulated with
      interleukins-4 and -13. The activation of the interleukin-4/13 receptor(s)
      appears to be mandatory, but not sufficient, for 15-lipoxygenase gene expression.

PMID- 8761487
TI  - Regulation of glucose transporters (GLUT-1 and GLUT-3) in human retinal
      endothelial cells.
AB  - The regulation of glucose transporters (GLUT-1 and GLUT-3), in terms of both mRNA
      and protein, in human retinal endothelial cells was investigated. The cells
      responded within 1 h of exposure to 5 mM glucose with an increase in the level of
      GLUT-3 mRNA that was due to an increase in the transcription of the 4.1 kb mRNA
      of the gene for GLUT-3. In the absence of glucose, the gene for GLUT-1 was not
      transcribed but the level of GLUT-3 mRNA was increased in these conditions and
      this was the result of an increase in the transcription of the 4.1 kb mRNA. The
      level of GLUT-1 and GLUT-3 mRNA was maximal when the cells were exposed to 15 mM
      glucose. These results are discussed in the light of the glucose regulatory
      potential of the retinal microvasculature and the implications that this may have
      for the mechanisms of diabetic retinopathy.

PMID- 8761488
TI  - Different mucins are produced by the surface epithelium and the submucosa in
      human trachea: identification of MUC5AC as a major mucin from the goblet cells.
AB  - Mucins were extracted from the epithelial surface and the submucosal tissue of
      human trachea in order to enrich glycoproteins from the goblet cells and the
      submucosal glands respectively. The macromolecules were purified using density
      gradient centrifugation, and the presence of the MUC5AC mucin was investigated
      using an antiserum raised against a synthetic peptide based on the sequence of
      the MUC5AC apoprotein. Mucins from the surface epithelium showed a higher
      reactivity with the antiserum relative to carbohydrate than those from the
      submucosa, and ion-exchange HPLC of reduced subunits revealed the presence of two
      distinct mucin populations in the samples. The predominant species from the
      surface epithelium was more acidic than the major population from the submucosa
      and showed a strong reactivity with the anti-MUC5AC anti-serum. In contrast, the
      major portion of the submucosal mucins were less acidic and showed no MUC5AC
      reactivity, although a more acidic population did react with the antibody. Rate
      zonal centrifugation showed that the MUC5AC mucin from the surface epithelium is
      smaller than the major submucosal mucin, and that both are composed of subunits.
      Immunolocalization confirmed that the MUC5AC mucin from human trachea originates
      from the goblet cells and that this glycoprotein is not a major product of the
      submucosal glands.

PMID- 8761489
TI  - Down-regulation of cytokine-induced cyclo-oxygenase-2 transcript isoforms by
      dexamethasone: evidence for post-transcriptional regulation.
AB  - The immediate-early cyclo-oxygenase-2 (Cox-2) gene encodes an inducible
      prostaglandin synthase enzyme that has been implicated in inflammatory and
      proliferative diseases. We have shown that the inflammatory cytokine interleukin
      1 (IL-1) induces the Cox-2 gene in a sustained manner and that post
      transcriptional mRNA stabilization is an important even [Ristimaki, Garfinkel,
      Wessendorf, Maciag and Hla (1994) J. Biol. Chem. 269, 11769-11775]. The anti
      inflammatory glucocorticoid dexamethasone potently down-regulates IL-1-induced
      Cox-2 mRNA expression. Kinetic studies suggest that antagonism of IL-1-induced
      mRNA stabilization is, at least in part, responsible for the suppression of Cox-2
      mRNA. The Cox-2 gene produces two major transcript isoforms, namely Cox-2(4.6)
      (4.6 kb) and Cox-2(2.8) (2.8 kb), which are derived by alternative
      polyadenylation in the 3'-untranslated region (UTR). In response to
      dexamethasone, the short Cox-2(2.8) transcript isoform, which lacks a highly
      conserved AU-rich region, decays with a longer half-life than the Cox-2(4.6)
      isoform. Furthermore, heterologous expression of the hybrid Cox-1 open reading
      frame and the Cox-2 3'-UTR results in the accumulation of high levels of the
      short isoform and lower levels of the long isoform. These data suggest that
      multiple elements in the 3'-UTR of the Cox-2 gene are involved in the
      determination of the differential mRNA stabilities of Cox-2 transcript isoforms.
      Because dexamethasone destabilizes the Cox-2 transcript, and because the decay of
      Cox-2 transcript isoforms induced by dexamethasone occurs with different half
      lives, post-transcriptional mRNA destabilization may be an important mechanism in
      the action of anti-inflammatory glucocorticoids.

PMID- 8761490
TI  - Betamethasone modulation of sphingomyelin hydrolysis up-regulates
      CTP:cholinephosphate cytidylyltransferase activity in adult rat lung.
AB  - Glucocorticoids appear to play an integral role in stimulating surfactant
      synthesis by activating the rate-regulatory enzyme for phosphatidylcholine
      synthesis, CTP:cholinephosphate cytidylyltransferase (CT). The activity of liver
      CT, in vitro, has been shown to be inhibited by the sphingomyelin hydrolysis
      product, sphingosine. In order to investigate the mechanisms by which
      glucocorticoids alter CT activity, in vivo, we administered betamethasone (1
      mg/kg intraperitoneally) sequentially to adult male rats for 5 days.
      Betamethasone increased CT activity 2-fold relative to control in whole lung. The
      hormone also increased membrane-bound activity, but did not affect cytosolic
      enzyme activity. Betamethasone modestly increased CT mRNA as determined by the
      reverse-transcription PCR and Southern analysis of PCR products, but did not
      alter the levels of immunoreactive enzyme in lung membranes as demonstrated by
      Western blotting. The hormone did, however, produce a nearly 3-fold increase in
      membrane-associated sphingomyelin, and co-ordinately a substantial decrease in
      the levels of sphingosine in lung membranes. Sphingosine, but not sphinganine,
      was a competitive, reversible inhibitor of lung CT with respect to the enzyme
      activator, phosphatidylglycerol. Betamethasone decreased the activities of the
      sphingomyelin hydrolases: acid sphingomyelinase by 33% and of alkaline ceramidase
      by 21%. The hormone also inhibited the generation of sphingosine from
      lysosphingomyelin in lung membranes. There was no significant effect of the
      hormone on serine palmitoyltransferase activity, the first committed enzyme for
      sphingolipid biosynthesis. Further, administration of L-cycloserine, an inhibitor
      of sphingosine formation, was shown to stimulate CT activity by 74% and increase
      disaturated phosphatidylcholine in alveolar lavage by 52% relative to control.
      These observations suggest that glucocorticoids up-regulate surfactant synthesis
      at the level of a key regulatory enzyme by significantly altering the
      availability of inhibitory metabolites resulting from sphingomyelin hydrolysis.

PMID- 8761491
TI  - Large-scale chromatographic purification of F1F0-ATPase and complex I from bovine
      heart mitochondria.
AB  - A new chromatographic procedure has been developed for the isolation of F1F0
      ATPase and NADH:ubiquinone oxidoreductase (complex I) from a single batch of
      bovine heart mitochondria. The method employed dodecyl beta-delta-maltoside, a
      monodisperse, homogeneous detergent in which many respiratory complexes exhibit
      high activity, for solubilization and subsequent purification by ammonium
      sulphate fractionation and column chromatography. A combination of anion
      exchange, gel-filtration, and dye-ligand affinity chromatography was used to
      purify both complexes to homogeneity. The F1F0-ATPase preparation contains only
      the 16 known subunits of the enzyme. It has oligomycin-sensitive ATP hydrolysis
      activity and, as demonstrated elsewhere, when reconstituted into lipid vesicles
      it is capable of ATP-dependent proton pumping and of ATP synthesis driven by a
      proton gradient [Groth and Walker (1996) Biochem. J. 318, 351-357]. The complex I
      preparation contains all of the subunits identified in other preparations of the
      enzyme, and has rotenone-sensitive NADH:ubiquinone oxidoreductase and
      NADH:ferricyanide oxidoreductase activities. The procedure is rapid and
      reproducible, yielding 50-80 mg of purified F1F0-ATPase and 20-40 mg of purified
      complex I from 1 g of mitochondrial membranes. Both preparations are devoid of
      phospholipids, and gel filtration and dynamic light scattering experiments
      indicate that they are monodisperse. Therefore, the preparations fulfil important
      prerequisites for structural analysis.

PMID- 8761492
TI  - ATP synthase from bovine heart mitochondria: reconstitution into unilamellar
      phospholipid vesicles of the pure enzyme in a functional state.
AB  - A highly purified and monodisperse preparation of proton-translocating F1F0
      ATPase from bovine heart mitochondria is an assembly of 16 unlike polypeptides.
      This preparation has been reconstituted in the presence of various detergents
      into unilamellar phospholipid vesicles. Incorporation of the enzyme into vesicles
      increases the ATP hydrolase activity of the enzyme by 10-20-fold, depending on
      the detergent, and the highest activities of ATP hydrolysis, 70 units/mg, were
      obtained by reconstitution from dodecylmaltoside or CHAPS. This activity is
      mostly sensitive to inhibitors that act on the F0 membrane sector of the complex.
      From the quenching of the pH-sensitive probe, 9-amino-6-chloro-2-methoxyacridine,
      it was shown that the reconstituted enzyme was able to form a transmembrane
      proton gradient in an ATP-dependent manner. By co-reconstitution of the enzyme
      with bacteriorhodopsin, it was demonstrated that in the presence of a light
      induced proton gradient the enzyme can synthesize ATP from ADP and phosphate.
      Therefore, the characteristic biological functions of the F1F0-ATPase in
      mitochondria have been demonstrated with the purified enzyme. Thus, in terms of
      both its physical and biochemical properties, the purified enzyme fulfils
      important pre-requisites for formation of two- and three-dimensional crystals.

PMID- 8761493
TI  - The PL/IM 430 and the N 89 antibodies recognize two distinct 97 kDa
      sarco/endoplasmic-reticulum Ca(2+)-ATPase proteins.

PMID- 8761495
TI  - Learning and change.

PMID- 8761494
TI  - Sequence of bovine carbonic anhydrase VI: potential recognition sites for N
      acetylgalactosaminyltransferase.
AB  - Carbonic anhydrases (CAs I-VII) are products of a gene family that encodes seven
      isoenzymes and several CA-related proteins. We report the cloning and sequencing
      of the cDNA clones encoding one of these isoenzymes, CA VI, from bovine
      submaxillary gland. The translated polypeptide consists of 319 amino acids,
      including a signal peptide (14 amino acids) typical of secreted proteins. The
      predicted mature protein contains 305 amino acids including a 13-amino-acid C
      terminal sequence that is also present in the sheep but absent in human CA VI.
      The deduced mature bovine protein is 87% and 68% identical to that of sheep and
      human CA VI, respectively. Active-site residues of the enzyme, as well as the
      three zinc-binding histidines and the two cysteines involved in an intra-chain
      disulphide bond, are all conserved in the three species. Two potential Asn
      glycosylation sites are also conserved, both of which appear to be glycosylated
      in sheep and bovine CA VI. Two potential peptide recognition sequences are
      present in bovine CA VI for the glycoprotein hormone: N
      acetylgalactosaminyltransferase (GalNAc-transferase), which is one of the two
      transferases required to form GalNAc-4-SO4 in bovine CA VI-linked
      oligosaccharides. Specifically, these two sequences are Asp-Leu-Lys-Met-Lys-Lys
      and Ile-Thr-Lys-Arg-Lys-Lys. Comparison of these sequences with sheep and human
      CA VI sequences indicates that distinct glycoforms of CA VI could exist in
      submaxillary gland from different species.

PMID- 8761496
TI  - The evaluation and management of subclinical pituitary disease.
AB  - The advent of sophisticated and sensitive radiologic techniques has undoubtedly
      improved the evaluation of patients with established endocrine disease. An
      inevitable consequence of the increased sensitivity and widespread availability
      of modern imaging is, however, the discovery of apparently asymptomatic mass
      lesions in endocrine tissues. The clinician is then required to determine the
      appropriate degree of often uncomfortable and costly investigation in a patient
      with no overt disease. This article attempts to provide guidelines for the
      management of the 'pituitary incidentaloma', a pituitary mass lesion evident on a
      computed tomography or magnetic resonance imaging scan performed for a reason
      other than the evaluation of the pituitary gland.

PMID- 8761497
TI  - The diabetic patient with hypertension.
AB  - Hypertension and diabetes co-exist more commonly than would be expected from
      their individual prevalences. Elevated blood pressure is most commonly due to
      coexisting essential hypertension, or diabetic renal disease. Early stages of
      diabetic renal disease can be identified by detecting microalbuminuria. Standard
      measures of blood pressure are not necessarily raised, but 24-hour ambulatory
      measures frequently identify a loss of nocturnal drop in blood pressure. Treating
      hypertension aggressively is important in slowing the inexorable decline in
      glomerular filtration rate. In diabetes there appears to be no 'J'-shaped
      relationship between blood pressure and cardiovascular events, thus removing any
      concern about attaining low blood pressures as long as the patient is
      asymptomatic. Morbidity and mortality in these patients is usually associated
      with cardiovascular events, and it is important to assess the effect of drugs on
      left ventricular hypertrophy and metabolic parameters. Many drugs are effective
      at lowering blood pressure, but angiotensin-converting enzyme inhibitors may have
      an additional renoprotective action. alpha-Adrenergic antagonists may improve
      lipid profiles and calcium antagonists are probably lipid neutral, making these
      drugs useful alternatives. Dihydropyridine calcium antagonists (eg, nifedipine)
      may augment protein-uria, and hence non-dihydropyridine calcium antagonists (eg,
      verapamil, diltiazem) would be preferred. beta-Blockers and thiazide diuretics
      have the disadvantage of causing a deterioration in glycaemic and lipid profiles,
      but can be useful on occasions.

PMID- 8761498
TI  - Primary coronary angioplasty in acute myocardial infarction.
AB  - It is well established that recanalisation of the infarct-related artery is of
      great benefit in the early hours after acute myocardial infarction. This can be
      achieved by the use of thrombolytic agents and/or by percutaneous transluminal
      coronary angioplasty (PTCA). This article reviews data on the role of primary
      PTCA and summarises current opinion on its use.

PMID- 8761499
TI  - Coronary artery stents.
AB  - The use of coronary stents to treat the acute complications of percutaneous
      transluminal coronary angioplasty and to reduce the restenosis rate following
      this procedure is reviewed.

PMID- 8761500
TI  - Acute pancreatitis: assessment and management.
AB  - In the 1920s Moynihan described acute pancreatitis as "..the most terrible of all
      intra-abdominal calamities". He established a practice of immediate surgical
      intervention to remove the toxic products accumulating in the peritoneal cavity,
      and this treatment was endorsed by most centres, remaining the standard therapy
      for the next 20 years. In the 1940s, the mortality of patients treated surgically
      was shown to be far higher than those treated conservatively, and a more
      conservative line of management was recommended, comprising nasogastric stomach
      decompression, intravenous fluid therapy, opiate analgesia, and the
      administration of atropine. Despite half a century passing, a clinician would not
      be criticised for adopting such a regime today, which in part reflects the lack
      of understanding of this condition and the failure of seemingly appropriate
      therapy. Reduction in mortality is a consequence of advances in intensive care
      preventing the high early mortality of organ failure, but the area of specific
      therapy remains elusive. While this is so, the mortality rates for these patients
      will remain static, while the doctor continues to feel clinically impotent.

PMID- 8761501
TI  - Contract learning, clinical learning and clinicians.
AB  - Current trends in education and training emphasise that learners, whether they
      are school children, students or adults, need to acquire generic skills and
      personal characteristics which will enable them to become independent self
      directed learners. This will enable them to continue the process of learning
      throughout their lives. Recent recommendations for the reform of undergraduate
      medical education, for training of hospital doctors and general practitioners,
      and the higher profile now being given to continuing medical education, reflect
      the strength of this particular educational current sweeping through all levels
      of medical education. Learning contracts, developed through negotiation between a
      teacher and a learner, are especially effective educational tools for stimulating
      independent learning. This paper examines the theoretical basis of contract
      learning and its relevance to clinical settings.

PMID- 8761502
TI  - The distribution of antibodies to streptokinase.
AB  - To determine the distribution of antibodies to streptokinase that might be
      anticipated in patients requiring treatment with streptokinase, specific anti
      streptokinase antibody titres were determined in a group of subjects from the
      general population and in a group of patients presenting with acute myocardial
      infarction. Enzyme-linked immunosorbent assays were developed to measure specific
      anti-streptokinase IgG and subclass IgG1 in 95 subjects from the general
      population and in 160 patients presenting with acute myocardial infarction. Low
      titres of IgG1 were found in both the general population (median = 5; range: 0
      490) and in the myocardial infarction group (median = 7; range: 0-2000). A
      minority of subjects in both groups had high titres. The findings suggest that
      low titres of antibody are widespread in the population. The minority of subjects
      in both groups who had high titres may explain the infrequent type III immune
      reactions encountered with streptokinase.

PMID- 8761503
TI  - Nocturnal and respiratory disturbances in Steele-Richardson-Olszewski syndrome
      (progressive supranuclear palsy).
AB  - Respiratory and sleep disturbances may be important causes of morbidity in Steele
      Richardson-Olszewski syndrome but the frequency and character of nocturnal
      abnormalities remains uncertain. A prospective study of 11 patients with Steele
      Richardson-Olszewski syndrome and age-matched control subjects was undertaken
      using clinical assessments, a structured sleep questionnaire, spirometry, static
      maximum inspiratory and expiratory pressures and nocturnal oximetry. The mean age
      of the Steele-Richardson-Olszewski syndrome patients was 63.2 (52-70) years and
      mean disease duration was 4.0 (2-6) years. There was moderate to severe motor
      disability in nine and mild to moderate dementia in eight. In the patients with
      Steele-Richardson-Olszewski syndrome the following abnormalities contributed to
      sleep disturbances significantly more frequently than in normal controls:
      depression, dysphagia, frequent nocturnal awakenings (usually associated with
      urinary frequency), immobility in bed, difficulty with transfers, impaired
      dressing and feeding. There was profound impairment of voluntary respiratory
      control whilst automatic and limbic control were well maintained. Nocturnal
      respiratory abnormalities were not present even in the most severely disabled. In
      Steele-Richardson-Olszewski syndrome sleep abnormalities are common; they relate
      to the cognitive, pseudobulbar and extrapyramidal disturbances and may therefore
      be amenable to symptomatic control.

PMID- 8761504
TI  - Polymicrobial brain abscess involving Haemophilus paraphrophilus and Actinomyces
      odontolyticus.
AB  - A case of brain abscess involving Haemophilus paraphrophilus and Actinomyces
      odontolyticus is presented. This combination of organisms has not previously been
      described. All brain abscess specimens should routinely be processed rapidly and
      cultured for a prolonged period to ensure recovery of fastidious organisms which
      may have implications for antibiotic therapy.

PMID- 8761505
TI  - Gallbladder wall thickening in infectious mononucleosis: an ominous sign.
AB  - Gallbladder wall thickening (3 mm or greater) is a nonspecific finding with many
      causes. We describe two cases caused by infectious mononucleosis. Other causes of
      gallbladder wall thickening are described and the literature is reviewed. We
      suggest that the finding of gallbladder wall thickening in a patient with
      infectious mononucleosis implies that the patient is very ill, and its
      observation should lead to close patient monitoring.

PMID- 8761506
TI  - Gallstone ileus--beware the silent second stone.
AB  - Gallstone ileus remains a rare but important cause of small bowel obstruction. We
      report a case of recurrent gallstone ileus, presumably caused by an unidentified
      second stone resident within the gallbladder at the time of the initial
      laparotomy. This raises important questions about the traditional surgical
      management of this interesting condition.

PMID- 8761507
TI  - Transitional cell carcinoma of the bladder in an HIV-infected patient.
AB  - A case of transitional cell carcinoma of the urinary bladder in a patient
      infected with the human immunodeficiency virus is reported. The tumour was very
      large, occupying most of the bladder, however cystoscopic removal of the tumour
      was successful with no recurrence after one year. This association has never
      reported before. The possible contribution of human immunodeficiency virus
      infection to its occurrence is discussed.

PMID- 8761508
TI  - Spindle cell stromal tumour of the rectum treated by restorative resection.
AB  - Stromal tumours of the rectum and anal canal are rare, representing 0.02-0.03% of
      malignant neoplasms in the region. Current advice in their management is
      treatment by abdomino-perineal resection. We report a case of malignant spindle
      cell stromal tumour in which adequate clearance was obtained whilst preserving
      the anal sphincter, using a posterior parasacral approach.

PMID- 8761509
TI  - Intestinal obstruction in an adolescent female.

PMID- 8761510
TI  - An ominous complication of acute myocardial infarction.

PMID- 8761512
TI  - Gerstmann's syndrome.
AB  - Although Gerstmann's syndrome has been well documented since it was characterised
      in the latter half of last century, there has not been much literature on it in
      the last few years. We present a classical case in a patient who was admitted
      into hospital for an unrelated problem. We conclude that clinical examination
      still has a valuable role in neurology, despite the availability of excellent
      imaging techniques.

PMID- 8761511
TI  - Spontaneous aortic rupture in a 22-year-old.

PMID- 8761513
TI  - Puerperal subdural empyema.

PMID- 8761514
TI  - Discussing CPR with patients and relatives.

PMID- 8761515
TI  - Polymyalgia rheumatica, temporal arteritis and malignancy.

PMID- 8761516
TI  - Management of acute myocardial infarction.

PMID- 8761517
TI  - Solubility of hydroxyapatite/mica composites.
AB  - The solubility of some inorganic materials was studied. It was found that Ca
      dissolution was high in calcium phosphates with Ca/P ratios 1.67-2.0. Dissolution
      of P was moderate compared with dissolution of Ca. The composites, HA content 70
      wt-%, and HA showed to be corrosion resistant. Dissolution of alumina in the
      mineral muscovite, used as a filler material, was found to be neglectable and
      dependent on the density of the composite.

PMID- 8761519
TI  - Dentin bonding system. Part II: Effect of crosshead speed.
AB  - Dentin bond strengths are normally evaluated by conducting mechanical tests in
      tensile and/or shear mode at a certain level of crosshead speed. According to the
      literature review, crosshead speed is varied in a relatively wide range from 0.1
      mm/min to 10.0 mm/min (with the exception of a few studies conducted above 10.0
      mm/min). It was also found that crosshead speeds of 0.5, 1.0, 2.0 and 5.0 mm/min
      were commonly employed to evaluate dentin bond strengths for both tensile and
      shear modes, although no rationale for selecting the crosshead speed was
      described in the articles. For testing dentin bond strengths, no plastic
      deformation should be involved, and fracture only should take place during the
      fracturing process. With the Scotchbond Multiple-Purpose/Z100 bonding system,
      tensile bond strengths were evaluated at crosshead speeds of 0.1, 0.5, 1.0, 5.0
      and 10.0 mm/min. It was found that (i) there was no strain rate sensitivity when
      the test was conducted below the 1.0 mm/min crosshead speed, and (ii) if the
      crosshead speed exceeded 1.0 mm/min, a strain rate dependency of the tensile bond
      strengths was observed. Knowledge that the composite resin (Z100) did not exhibit
      strain rate dependency influenced the conclusion that (iii) the above observed
      strain rate dependency was solely due to the mechanical response from the bonding
      interface region.

PMID- 8761518
TI  - Effect of Ti, Al, and V ions on the relative growth rate of fibroblasts (L929)
      and osteoblasts (MC3T3-E1) cells.
AB  - The effect of Ti, V and Al ions on the relative growth rate of L929 cells and
      MC3T3-E1 cells was investigated by a cell culture method with metallic powders.
      These powders were sterilized under a U.V. lamp for 6 h, suspended in the medium
      and extracted for 48 h, 72 h and 96 h in the incubator. After filtering with a
      0.2 microns filter, 3.0 x 10(4) L929 cells and 5 x 10(4) MC3T3-E1 cells were
      seeded in these filtrates of the medium with and without (control) the presence
      of the metallic powder. The number of cells was counted using a coulter counter
      from 1 to 7 days. The number of L929 cells after 4 days of incubation was almost
      similar for Ti and the control, whereas in the case of A1 and V extraction the
      number of cells was too low as compared to that of the control. The relative
      growth rate of L929 cells for Ti, A1 and V after 4 days of incubation was about
      1, 0.2 and 0.02, respectively. A similar trend was also observed for MC3T3-E1
      cells. The effect of the relative growth rate of L929 cells at different
      extraction times of 48 h, 72 h and 96 h was examined. It was found that the
      relative growth rate of L929 cells for Ti, A1 and V extraction was almost the
      same at all three extraction times. A number of 2.0-5.0 x 10(4) cells was seeded
      in the medium of A1 extraction. The effect of this initial number of cells on the
      relative growth rate of L929 cells was investigated. The relative growth rate of
      L929 cells decreased as the initial number of L929 cells increased. Moreover,
      dilutions from 1 to 10 times in the case of A1 and from 1 to 4000 times in the
      case of V were made. The relative growth rate became equal to 1 at 5 times
      dilution for A1 and at 4000 times dilution for V, for both L929 and MC3T3-E1
      cells. From the measures of the concentration of the released A1 and V ions on
      the relative growth rate of L929 cells, it could be seen that there was a marked
      decrease in the concentrations of A1 and V ions from 0.3 ppm to 0.1 ppm.

PMID- 8761520
TI  - Carbonate hydroxyapatite gel monolith formation and drying.
AB  - The effect of carbonate in reducing the crystal size of precipitated
      hydroxyapatite by approximately an order of magnitude has not been used
      previously in the preparation of gel monoliths for the fabrication of carbonate
      hydroxyapatite ceramics. The aim of this study was to devise a method whereby gel
      monoliths of carbonate hydroxyapatite could be repeatably produced without
      cracking. A precipitation reaction was used for the preparation of carbonate
      hydroxyapatities with carbonate contents of 5.8 and 7.8 wt%. Biaxial vacuum
      filtration was used to form disc shaped monoliths. The rate of filtration of a
      7.8 wt% carbonate hydroxyapatite sol was measured throughout the gelation
      process. Gel monoliths were dried slowly in air and the mass and dimensions of
      the gel were recorded once approximately every 24 hours. Using this data, the
      permeability, water volume fraction with time, rate of water loss, gelation point
      and gel density were determined. The pore size distribution was measured using
      mercury porosimetry for a carbonate apatite gel and a pressed powder pellet of a
      commercial hydroxyapatite. In tact monoliths were formed with masses up to 9.9 g.
      It was found that gelation behaviour was independent of monolith size and
      carbonate content and the final green density of all monoliths was 37%. Gelation
      was found to occur at 50-55 vol% water. Gel monoliths were found to have a
      monomodal pore size distribution with a mean pore size of 9.1 nm, whereas a
      pressed pellet of hydroxyapatite had a bimodal pore size distribution.

PMID- 8761521
TI  - Effect of debonding forces on bonded orthodontic brackets: finite element study.
AB  - The finite element analysis method was used to obtain values of the von Mises
      equivalent stress (SEQV) at selected locations within the adhesive layer of two
      dimensional models of bonded orthodontic brackets. In all, 39 model cases were
      analyzed involving 4 overall bracket configurations, 3 combinations of materials
      of fabrication of the bracket, 3 types of debonding forces and 4 adhesives. The
      results are presented to show the sensitivity of SEQV to each of the parameters
      studied. Comments are made on the usefulness of the results in the development of
      a standard protocol for experimental determination of the bond strength of
      adhesives used in securing orthodontic brackets.

PMID- 8761522
TI  - Prevention of platelet adhesion on polysulfone porous catheter by saline solution
      perfusion, II. Ex vivo and in vivo investigation.
AB  - Using a custom-made PVC medical tube ateriovenous (A-V) shunt and a porous
      polysulfone (PSf) catheter, an ex vivo and in vivo experiment were carried out to
      study the effectiveness of saline solution perfusion to prevent adhesion of
      platelets without using anticoagulants. The critical perfusion rate for
      preventing adhesion of platelets onto the PSf catheter tubes is about 0.45 ml min
      1 cm-2. The higher perfusion rate resulted in a lesser platelet adhesion. At the
      highest perfusion rate tested, 0.92 ml min-1 cm-2, the number of adhered
      platelets decreased by 98% in the in vivo experiment. From the results of ex vivo
      and in vivo canine experiments, the saline perfusion catheters can be used as a
      very useful clinical armamentarium to prevent platelet and blood cell adhesion
      without using anticoagulants.

PMID- 8761523
TI  - Metrology and analysis in laboratory medicine: a criticism from the workbench.
AB  - Metrological concepts and terminology, in particular the Vocabulaire
      International des Termes Fondamentaux et Generaux de Metrologie and the Guide to
      the Expression of Uncertainty in Measurement, are discussed from the viewpoint of
      analytical practice. Especially addressed are terms such as error, uncertainty,
      accuracy, trueness, bias, and precision. Evidence is presented that the new
      definition of accuracy, being now a joint index of systematic and random errors,
      is extremely impractical and has no advantages over the old definition of
      accuracy. Therefore, instead of re-education of analysts, a return to the old
      definition is proposed. Further, arguments are presented that the error concept
      is still an extremely useful metrological concept and does not need to be
      replaced by the uncertainty concept. Rather, both concepts are complementary.

PMID- 8761524
TI  - Lipid composition of mononuclear cell membranes and serum from persons with high
      or low levels of serum HDL cholesterol.
AB  - High density lipoprotein (HDL) levels have been shown to be inversely correlated
      with the incidence of coronary artery disease (CAD). Since we have previously
      found that peripheral blood mononuclear cells (PBMC) from persons with high (n =
      10) or low HDL (n = 10) have different functional properties, we wanted to
      examine the PBMC membrane lipid composition and fluidity, as well as to
      characterize the serum lipoproteins in greater detail. In persons with high HDL,
      PBMC membrane phospholipids were higher, and the cholesterol/phospholipid (CH/PL)
      ratio lower than in persons with low HDL. Membrane cholesterol and phospholipids
      were positively correlated with serum HDL2. The fatty acid composition of
      membrane phospholipids, and membrane fluidity was similar. The median
      saturated/unsaturated fatty acid (SFA/UFA) ratio tended to be lower in PBMC
      membranes and in serum from persons with high HDL; however this was not
      statistically significant. In serum, total phospholipids and HDL2 components
      (cholesterol, phospholipids and protein) were higher in persons with high HDL,
      whereas non-esterified fatty acids (NEFA) and very low density lipoprotein (VLDL)
      components (triglycerides, cholesterol, phospholipids and protein) were lower.
      Furthermore, serum cholesterol esters and the cholesterol esters/free cholesterol
      (CE/FC) ratio was higher, and the atherogenic index, i.e. (apoB X (total
      cholesterol-HDLc)/apoA-I X HDLc, lower in persons with high HDL. These results
      demonstrate that PBMC from persons with high or low serum HDL have a different
      lipid composition presumably of importance for cell function, lipid transport and
      atherogenesis.

PMID- 8761525
TI  - Studies on the degradation of [U-3H]-phytanic acid and [U-3H]-pristanic acid in
      cultured fibroblasts from children with peroxisomal disorders.
AB  - Up till now, errors of phytanic acid metabolism in children with peroxisomal
      disorders have been estimated by measuring 14CO2 formation from 1-14C-labelled
      phytanic acid in different systems. In the present work we have incubated both 1
      14C- and U-3H-labelled phytanic acid and U-3H-labelled pristanic acid with
      cultured fibroblasts from healthy children as well as from children with
      peroxisomal disorders. In cultured fibroblasts from healthy children, [U-3H]
      pristanic acid was degraded at a rate 60 times that of [U-3H]-phytanic acid,
      indicating that the initial degradation of phytanic acid into pristanic acid is
      the rate-limiting step in the overall conversion. In cultured fibroblasts from
      children with the Zellweger syndrome and infantile Refsum disease, the
      degradation of both phytanic acid and pristanic acid, was severely impaired (10
      40 and 10-30 times, respectively), but the degradation of pristanic acid was
      still more than 20 times higher than that of phytanic acid in these disorders. In
      fibroblasts from a child with rhizomelic chondrodysplasia punctata the rate of
      degradation of U-3H- and 1-14C-labelled phytanic acid was markedly reduced
      whereas the rate of degradation of U-3H-labelled pristanic acid was normal. No
      evidence was obtained for elongation of phytanic or pristanic acid in the
      different fibroblastic cultures. It is concluded that both the degradation of
      phytanic acid and pristanic acid may be affected in peroxisomal disorders. The
      possibility that phytanic acidaemia in these disorders is due to product
      inhibition of accumulated pristanic acid seems to be excluded. The pristanic
      acidaemia sometimes seen is likely to be due to dietary pristanic acid rather
      than to de novo synthesized pristanic acid from accumulated phytanic acid.

PMID- 8761526
TI  - Metabolism of orally fed [3H]-eicosapentaenoic and [14C]-arachidonic acid in
      essential fatty acid-deficient rats.
AB  - The metabolism of individual polyunsaturated fatty acids (PUFA) may be influenced
      differently by nutritional status and nutritional intake. In normal rats,
      radioactive arachidonic acid (20:4(n-6), is preferentially retained in tissue
      phospholipids compared to linoleic (18:2(n-6), or eicosapentaenoic acid (20:5(n
      3). This study compares the fate of 20:4(n-6) and 20:5(n-3) acids in essential
      fatty acid-deficient (EFAD) rats. [3H]-20:5 and [14C]-20:4 were fed in a fish oil
      emulsion to EFAD rats. Tissue lipids were analysed for radioactivity at 1, 2 and
      4 h. The conversion of [3H]-20:5 to docosapentaenoic acid (22:5) and
      docosahexaenoic acid (22:6) was examined using high performance liquid
      chromatography (HPLC). The recovery of 3H in small intestine was lower than that
      of 14C (26 vs. 36% after 4 h, p < 0.001), but was higher in the liver (26 of 3H
      vs. 22% of 14C, p < 0.01), kidneys (1.5 vs. 1.2%, p < 0.001) and colon (0.3 vs.
      0.2%, p = 0.01). The percentages of 3H and 14C in phospholipids were investigated
      in intestine and liver, and were higher in EFAD rats than in normal rats,
      particularly for phosphatidylethanolamine (PE). The proportions of [3H]-20:5
      transformed to 22:5 and 22:6 did not exceed 7% in the intestine and 10% in the
      liver. In conclusion, the metabolism of dietary fatty acids 20:4 and 20:5
      differed less than in normal rats, mainly due to the preferential retention of
      both fatty acids in phospholipids.

PMID- 8761527
TI  - Phytosterolaemia in a Norwegian family: diagnosis and characterization of the
      first Scandinavian case.
AB  - Phytosterolaemia (sitosterolaemia) is a very rare inherited sterol storage
      disease characterized by tendon and tuberous xanthomas and by a predisposition to
      atherosclerosis. We here describe the first Scandinavian case. The 14-year-old
      female patient was found to have markedly elevated circulating levels of plant
      sterols (sitosterol, sitostanol, campesterol, stigmasterol), and the levels of
      these sterols were 20-50 times higher than in her healthy sister and heterozygous
      parents. In addition to the usual serum plant sterols we found a new major sterol
      in the patient tentatively identified as episterol or fecosterol (24-methyliden
      cholest-7 (or 8)-en-3 beta-ol). A newly developed method based on the use of
      deuterium labelled cholesterol and plant sterols was used to measure sterol
      absorption in the patient and her relatives. Absorption of sitosterol averaged
      20% in the patient and ranged from 4 to 8% in the relatives. Absorption of
      campesterol averaged 31% in the patient and ranged from 15 to 18% in her
      relatives. Absorption of cholesterol averaged 63% in the patient and ranged from
      35 to 45% in the relatives. Cholesterol synthesis appeared to be reduced in the
      patient and was 46-52% of that of her relatives.

PMID- 8761528
TI  - Variation in risk indicators of cardiovascular disease during the menstrual
      cycle: an investigation of within-subject variations in glutathione peroxidase,
      haemostatic variables, lipids and lipoproteins in healthy young women.
AB  - Variations in erythrocyte glutathione peroxidase activity, serum concentrations
      of lipids and lipoproteins and in blood coagulation and fibrinolysis during the
      menstrual cycle were studied in healthy young women. Blood samples were drawn
      twice a week for 9 weeks. A group of males was used for estimation of the
      influence on the results of factors which were not related to the menstrual
      cycle. Variations during the menstrual cycle were demonstrated in several of the
      factors analysed. The activity of glutathione peroxidase was lowest at ovulation.
      The clotting activity of factor II+ VII+X and the concentration of fibrinogen
      were lowest during mid-cycle, and the number of platelets increased in the
      follicular phase (days 5-9). Statistically significant variations in the
      fibrinolytic factors analysed (tissue plasminogen activator (t-PA) and
      plasminogen activator inhibitor (PAI) were not observed during the menstrual
      cycle. The serum concentrations of cholesterol and LDL cholesterol were
      significantly higher at the start of the menstrual cycle (days 3-8) than later in
      the cycle (days 19-24). The concentration of HDL cholesterol was lowest in the
      late luteal phase (days 23-28).

PMID- 8761529
TI  - An exploration of intrapulmonary insulin administration in anaesthetized and
      mechanically ventilated pigs.
AB  - We investigated the efficacy of intrapulmonary administration of short-acting
      porcine insulin in anaesthetized pigs (n = 14) in a randomized intervention
      study. Insulin was administered by a new jet nebulizer (Maxin) in a random order
      at different doses, 0 (saline), 10 or 40 U. The hypoglycaemic effect was compared
      to control (0.9% saline). Blood glucose and serum insulin concentrations were
      followed at specified time intervals for 90 min. Plasma catecholamine
      concentrations were measured in order to estimate the concurrent stress.
      Nebulized insulin caused a significant decrease in blood glucose concentrations
      (p < 0.0001) (n = 28) at all doses used. The decrease in mean blood glucose
      concentration from the start of nebulization was 39 +/- 3% (mean +/- SEM),
      falling from 4.6 +/- 0.1 to 2.8 +/- 0.2 mmol 1(-1), with a nadir at 40 min after
      the 40 U insulin dose (n = 10). Serum insulin concentration rose from (mean +/-
      SEM) 5.2 +/- 0.1 to 25 +/- 9 mU 1(-1) after the insulin dose of 40 U (n = 10),
      the peak value occurred at 30 min. The plasma catecholamine concentrations
      increased significantly (p < 0.0001) (n = 28) from 0 to 60 min, this increase was
      similar for control and for different insulin doses. We conclude that
      intrapulmonary administration of insulin can cause a significant decrease in
      blood glucose concentrations in anaesthetized and mechanically ventilated pigs
      and results in clinically relevant serum insulin levels. Similar effects in
      humans would make inhaled insulin possible for clinical use.

PMID- 8761530
TI  - Assessment of dimethylxanthine formation from caffeine in healthy adults:
      comparison between plasma and saliva concentrations and urinary excretion of
      metabolites.
AB  - Caffeine (CA), paraxanthine (PX), theobromine (TB) and theophylline (TP) were
      determined in plasma (i.e. total concentrations), ultrafiltrate of plasma (free
      concentrations) and saliva, by isocratic high performance liquid chromatography
      (HPLC), 0-24 h after a 200 mg oral load of CA in 10 healthy adults. Total
      metabolism of CA was established by determination of urinary metabolites, 24 h
      after CA ingestion, by gradient HPLC and capillary electrophoresis. Saliva
      concentrations of CA, PX, and TP were lower than plasma concentrations (p <
      0.001), whereas TB concentrations in plasma and saliva were similar. Saliva
      concentrations of CA, PX, TB and TP were higher than the free plasma
      concentrations (p < 0.001). The area under the plasma concentration-time curve
      (AUC) showed that PX accounted for 63 +/- 13% of the dimethylxanthines in plasma,
      while TB accounted for 27 +/- 15% and TP for 10 +/- 2.6%. In contrast, the urine
      analyses showed that 78 +/- 11% of the excreted metabolites were metabolized
      through the PX pathway, 14 +/- 8% through the TB pathway and 9 +/- 4% through the
      TP pathway. The percentage of the AUC for PX, TB and TP in plasma was similar to
      the percentage of each dimethylxanthine excreted unmetabolized in urine. The
      percentages of the AUC for PX and TB were correlated to the percentages of PX (r
      = 0.78, p < 0.001) and TB (r = 0.88, p < 0.001) in urine. The AUC for PX in
      plasma was lower than (p < 0.001) and correlated to the total PX pathway value (r
      = 0.95, p < 0.001) and the value for PX plus its specific metabolites in urine.
      The AUC for TB in plasma was higher than (p < 0.001) and correlated to the total
      TB pathway value (r = 0.93, p < 0.001) and the value for TB plus its specific
      metabolites in urine. The AUC for TP in plasma was similar to both the TP pathway
      value and the value for TP plus its specific metabolites in urine. It is
      concluded that the AUC for dimethylxanthines in plasma underestimates the
      formation of PX, overestimates the formation of TB and gives a similar formation
      of TP from CA, as judged from the urinary metabolites formed through the PX, TB,
      and TP pathways.

PMID- 8761531
TI  - Serum concentrations of prostate-specific antigen after diagnostic procedures and
      transurethral microwave thermotherapy of benign prostatic hyperplasia.
AB  - The objective was to study the effects of diagnostic and therapeutic procedures
      on serum prostate-specific antigen (PSA) concentration. Urethrocystoscopy in
      combination with digital rectal examination was followed by a moderate increase
      of serum PSA for 7-10 days. At 1 day after transurethral microwave thermotherapy
      (TUMT), an acute and pronounced effect on PSA was observed, which returned to
      baseline level after 4 weeks. The initial rise in serum PSA corresponded to a PSA
      density of 1.11, compared to 0.07 at baseline. The present data should be taken
      into consideration in conjunction with endoscopic evaluation of the lower urinary
      tract. Additionally, the acute effect on PSA after TUMT strongly suggests the
      ability of thermotherapy to induce cellular injury and death. One-year follow-up,
      however, was associated with increased PSA levels, indicating that only a minor
      part of the PSA-producing compartment was lost in the acute phase.

PMID- 8761532
TI  - Changes with age in the urinary excretion of hydroxylysylpyridinoline (HP) and
      lysylpyridinoline (LP).
AB  - There is increasing evidence that the measurement of urinary
      hydroxylysylpyridinoline (HP or PYD) and lysylpyridinoline (LP or DPD) by HPLC
      (high performance liquid chromatography) is potentially useful in clinical and
      pharmacological studies. HP and LP are promising markers of bone resorption
      because their levels in urine reflect the breakdown of mature collagen fibrils
      mainly of skeletal tissues. HP and LP are two non-reducible cross-links of mature
      collagen which are formed by a sequence of post-translational modifications. HP
      is a derivative of three residues of hydroxylysine and is present in almost all
      mature tissues (e.g. tendon. vessel walls, cartilage, dentine and bone). LP is a
      derivative of two residues of hydroxylysine and one residue of lysine and is
      present mainly in dentine and bone. Neither cross-link is found in normal human
      skin. We have isolated and purified HP and LP from commercially available bone
      gelatine by a preparative reverse-phase column HPLC. These two components were
      used as external standards for sample analysis. In the present study we analysed
      the urinary excretion of HP and LP in a group of 264 male and 279 female healthy
      subjects aged from 6 months to 65 years. A continuous decline of both cross-link
      components during childhood paralleled by a decrease of the HP:LP-ratio was
      observed. The levels of HP and LP were 2.5-5 times higher in infants (0.5-1 year)
      than in children (5-10 years) and 15-20 times higher than in adults (26-65
      years). After the age of 17 years, both parameters remained at low levels. These
      data allow a precise quantitative monitoring of bone resorption in patients with
      metabolic bone diseases or during pharmacological interventions.

PMID- 8761533
TI  - Study on long-term biological variability of erythrocyte sedimentation rate.
AB  - The aim of the study was the estimation of long-term within-subject variability
      of ESR. ESR was measured in 52 healthy persons of both sexes, aged 20-50 years,
      twice a month during 6 consecutive months, after the method of Westergren. The
      within-run imprecision, expressed as CV was 13.2% (mean value, x = 3.9 mm h-1)
      and 3.8% (x = 16.0 mm h-1) respectively. The analytical day-to-day imprecision,
      calculated by duplicate measurements during 23 consecutive days. was s = 0.6 mm h
      1. The medians from within-subject variances were 0.9 for men and 8.6 for women,
      respectively. The 90th percentiles were 11.3 for men and 40.6 for women,
      respectively. The critical differences based on the median value (dk50) were 3.1
      mm h-1 (men) and 8.3 mm h-1 (women). The critical differences based on the 90th
      percentile (dk90) are 9.5 mm h-1 (men) and 17.7 mm h-1 (women).

PMID- 8761534
TI  - Is it appropriate to offer dialysis to octogenarians? A modern conspiracy?

PMID- 8761535
TI  - A critique of the Canada/USA (CANUSA) Peritoneal Dialysis Study.

PMID- 8761536
TI  - Commentary on the findings of the CANUSA Study.

PMID- 8761537
TI  - Answers to all your questions about peritoneal urea clearance and nutrition in
      CAPD patients.
AB  - In summary, SA and a number of other indices related to nutritional status have
      been identified as being strongly predictive of outcome in CAPD patients.
      Evidence connecting these indices to KT/V urea, or even to protein intake,
      remains limited, however. Increased dialytic dose may well increase protein
      intake, but neither of these parameters have been shown prospectively to raise
      SA, total body nitrogen, or SGA status on a consistent basis. Studies addressing
      this issue, however, have been few and small, and more data are required. For
      now, we will likely continue to deal with malnutrition by attempting to raise
      small solute clearance and protein intake, but we should be aware that such
      measures will frequently be unsuccessful, and we must pay attention to other
      factors, particularly comorbidity. It is clear from this review that there are
      many unanswered questions relating to this topic and that, in particular, the
      effect of prospective increases in the dialytic dose needs to be further
      elucidated.

PMID- 8761538
TI  - Reduced calcium dialysis fluids: what's the point?

PMID- 8761539
TI  - Water channels in the peritoneum.

PMID- 8761541
TI  - The Japanese National Registry data on pediatric CAPD patients: a ten-year
      experience. A report of the Study Group of Pediatric PD Conference.
AB  - OBJECTIVE: Over the past 10 years, we have collected data on pediatric patients
      less than 16 years of age from the National Registry of CAPD (continuous
      ambulatory peritoneal dialysis). We present our experience with this population.
      DESIGN: The database details the patient number, age, weight, height, outcome,
      cause of death, reason for terminating CAPD therapy, peritonitis, and catheter
      survival. PATIENTS: Of the 434 patients (239 males, 195 females), 37 patients
      (8.5%) were under 1 year of age and 164 patients (37.8%) were under 6 years of
      age. About half of the patients were less than 20 kg in weight, clearly
      indicating that CAPD was the treatment of choice in young children. The duration
      on CAPD for these patients was less than 2 years for 233 patients (54%), and was
      5 years or more in 48 patients (11%). RESULTS: The outcome of the total patient
      population of 434 as of May, 1991, is as follows: 229 patients (52.8%) were being
      successfully treated with CAPD, 47 patients (10.8%) died, and 78 patients (18.0%)
      received a kidney transplantation. The patient survival rate was 85.6% at 3 years
      and 81.7% at 5 years. The technique survival rate was 74.9% at 3 years and 63.5%
      at 5 years. The rate of peritonitis was one episode over 28.6 patient-months. The
      mean catheter duration was 1.68 years. Peritonitis rate, catheter survival rate,
      and the rate of tunnel infection were worse in children less than 6 years of age
      than in older children. CONCLUSION: The excellent patient and technique survival
      rates indicate that CAPD is an effective treatment for children with end-stage
      renal disease in Japan. The high infection rates in younger children indicate
      that extra careful management is needed for this young age group.

PMID- 8761540
TI  - Long-term dialysis with low-calcium solution (1.0 mmol/L) in CAPD: effects on
      bone mineral metabolism. Collaborators of the Multicenter Study Group.
AB  - OBJECTIVE: Peritoneal dialysate solutions with conventionally high-calcium (Ca)
      concentrations (1.75 mmol/L) are now widely replaced by solutions with a lower,
      more physiological calcium content to prevent hypercalcemia in patients treated
      with oral calcium-containing phosphate binders and/or calcitriol. While there is
      still debate on how far the dialysate calcium should be lowered (1.25 mmol/L or
      less), little information is available concerning the effects of a long-term
      treatment with low-calcium solutions on secondary hyperparathyroidism and bone
      mineral metabolism in general. DESIGN: A prospective, randomized, controlled
      multicenter study to compare the effects of low-calcium (LCa, dialysate calcium
      1.0 mmol/L) versus standard-calcium dialysate solution (SCa, dialysate calcium
      1.75 mmol/L) on bone mineral metabolism in continuous ambulatory peritoneal
      dialysis (CAPD) patients over 2 years of treatment. SETTING: Nephrology and
      dialysis units of primary and tertiary hospitals in Germany and Switzerland.
      PATIENTS: All CAPD patients in the participating centers between 18 and 80 years
      of age, stable on CAPD for at least 1 month, free of aluminium bone disease or
      prior parathyroidectomy were invited to enter the study. Sixty-four patients
      could be randomly allotted to LCa (n = 35) or SCa (n = 29) treatment in a 2-year
      protocol; 34 finished the study as planned. INTERVENTIONS: Calcium carbonate
      (CaCO3) was given as oral phosphate binder to maintain serum phosphate < 2.0
      mmol/L. If hypercalcemia supervened, CaCO3 was exchanged stepwise for aluminium
      hydroxide (Al(OH)3), until normocalcemia was obtained. Patients received
      calcitriol (0.25 microgram/day per os) if parathyroid hormone (PTH) exceeded the
      upper limit of normal by a factor of 2 or more. MAIN OUTCOME MEASURES: We
      assessed total and ionized serum calcium, phosphate, serum aluminum, alkaline
      phosphatase, osteocalcin, PTH (intact molecule), and phosphate binder intake at
      regular intervals. Measurements of bone mineral density and hand skeleton x-rays
      were obtained at the start and after 6 months and 2 years, respectively. RESULTS:
      With LCa, mean total and ionized serum calcium levels were within the normal
      range (total Ca: 2.0-2.6 mmol/L; ionized Ca: 1.19-1.32 mmol/L), but throughout
      the treatment period were significantly lower than with SCa. The incidence of
      hypercalcemia (> 2.8 mmol/L) was three times higher in patients on SCa, despite
      the significantly higher amount of Al(OH)3 and less CaCO3 given in this group. In
      parallel, serum aluminum increased with SCa throughout the study, whereas it was
      slowly decreasing with LCa. Median PTH levels remained stable at about two times
      the upper limit of normal over the 2 years of study with LCa. However, 23% of the
      patients on LCa developed severe hyperparathyroidism, with PTH levels exceeding
      ten times the upper limit of normal compared to only 10.3% of the patients on
      SCa. With SCa, median PTH decreased towards near normal levels. Alkaline
      phosphatase and serum osteocalcin correlated positively with PTH levels. Bone
      mineral density was in the lower normal range in both groups and remained
      unchanged at the end of the study. Skeletal x-ray films showed only minor
      alterations in very few patients in both groups with no correlation to serum PTH
      or treatment modality. CONCLUSION: In CAPD patients low-calcium dialysate
      solutions can be used successfully over prolonged periods of time with stable
      control of serum calcium. The risk of hypercalcemia resulting from calcium
      containing phosphate binders and the need to use aluminum-containing phosphate
      binders is markedly diminished. However, there is a certain risk that severe
      secondary hyperparathyroidism with long-term LCa therapy will develop, even if
      normocalcemia is maintained. Thus, LCa dialysis requires close and continuous
      monitoring of PTH and bone metabolism.

PMID- 8761542
TI  - CAPD viability: a long-term comparison with hemodialysis.
AB  - OBJECTIVE: To compare the long-term viability of continuous ambulatory peritoneal
      dialysis (CAPD) to that of hemodialysis (HD). DESIGN: Retrospective study of
      patients of our institution starting dialysis between January 1, 1981, and
      December 31, 1993, and surviving for at least 2 months. PATIENTS: Five hundred
      and seventy-eight new patients (51.3% on CAPD and 48.6% on HD). MAIN OUTCOMES
      STUDIED: Cox-adjusted assessment of patient and technique survival, and of
      technique success. Differences in results for two successive periods of time.
      RESULTS: Patient survival did not differ between CAPD and HD after adjusting for
      age and comorbidity, and significantly improved in the second part of the follow
      up (1987-1993). Technique failure was significantly higher on CAPD, in which it
      was inversely related to age. The probability of a patient continuing on the
      first method of dialysis ("technique success") was significantly lower on CAPD
      than on HD, but the difference decreased progressively with age and disappeared
      in patients > or = 75 years. CONCLUSION: CAPD is as effective as HD in preserving
      life in uremic patients in the long-term, and gives better results in the older
      elderly. In adults, the lower technique success rate may not be a problem for
      patients with access to a good transplantation program; for others, this drawback
      must be weighed against the advantages of home treatment.

PMID- 8761543
TI  - IgG subclasses in CAPD patients.
AB  - OBJECTIVE: To make a comparison of serum levels of immunoglobulin G (IgG)
      subclasses in adult continuous ambulatory peritoneal dialysis (CAPD) patients
      with those in age- and sex-matched hemodialysis patients and healthy volunteers,
      and to analyze the contribution of removal of these proteins in peritoneal
      effluent to their plasma values. DESIGN: A cross-sectional study. SETTING: A
      renal unit of a university hospital. PATIENTS: Twenty-three CAPD patients, 21
      hemodialysis patients, and 21 healthy volunteers. Peritoneal transport studies
      were done in 8 of the 23 CAPD patients. METHODS: IgG subclasses were measured in
      serum by nephelometry. For the peritoneal transport studies an ELISA method on
      ethylenediamine tetracetic acid plasma was used. The same method was used in
      seven-to-ten-fold concentrated peritoneal dialysate. RESULTS: CAPD patients had
      lower IgG2 and IgG4 levels than hemodialysis patients and healthy volunteers (p <
      0.01). IgG2 values below 1.5 g/L were present in 43% of the CAPD patients (p <
      0.001 compared to healthy volunteers). Peritonitis incidence was not different
      between CAPD patients with low or normal IgG2 plasma levels. Peritoneal clearance
      of IgG3 was lower than that of the other subclasses. Evidence was obtained for a
      depressed synthesis of IgG2 and IgG4 in CAPD patients. The hypothesis that
      interleukin-2 may be involved in the low synthesis rate of IgG2 is discussed.
      CONCLUSION: Low serum IgG2 and IgG4 levels are present in stable, adult CAPD
      patients. These were not caused by increased peritoneal loss, but by decreased
      synthesis.

PMID- 8761544
TI  - Prescription and assessment of tidal peritoneal dialysis delivery with a specific
      equilibration test.
AB  - OBJECTIVE: To propose a simplified equilibration test specific for tidal
      peritoneal dialysis (TPD) that will overcome the inconveniences of the
      measurement of TPD peritoneal solute clearances through whole dialysate
      collection. This will enable the prediction of peritoneal creatinine and urea
      clearances, the suitability of patients for TPD, and routine assessment of TPD
      delivery. DESIGN: In a prospective study, patients had a standardized TPD run,
      and dialysate-to-plasma (D/P) ratios for creatinine and urea were calculated at
      various TPD and peritoneal equilibration test (PET) time points and on total TPD
      dialysate. Solute clearances were estimated and measured, and correlation
      coefficients were obtained among all these variables. SETTING: Dialysis unit of a
      pediatric nephrology department and patients' homes. PATIENTS: Eleven pediatric
      patients with end-stage renal disease in stable clinical conditions treated with
      TPD. INTERVENTIONS: Dialysate and blood sample collections. MAIN OUTCOME
      MEASURES: D/P ratios for creatinine and urea at the fifth and seventh TPD
      exchanges, at 15-, 30-, 60-, and 120-minute PET times, and on total TPD dialysate
      and TPD peritoneal creatinine and urea clearances. RESULTS: Correlation
      coefficients between PET-derived and total TPD dialysate-derived D/P ratios, and
      those between PET-derived and measured creatinine and urea clearances were more
      significant at the 120-minute PET time point compared with the other PET time
      points. Best correlations were obtained at the fifth and seventh TPD exchanges.
      D/P ratios for creatinine and urea of the fifth and seventh TPD exchanges
      correlated significantly with the D/P ratios calculated from total TPD dialysate.
      A significant correlation was also found between peritoneal creatinine and urea
      clearances on total dialysate volume (measured clearances) and those derived from
      the dialysate collection of the fifth and seventh TPD exchanges (estimated
      clearances)--that based on the seventh exchange being slightly more significant.
      Moreover, the estimated clearances derived from the seventh exchange were within
      10% of the measured value in 90.9% of patients both for creatinine and urea.
      CONCLUSION: The significant correlation between measured and estimated peritoneal
      creatinine and urea clearances and the low percentage of underestimates of
      measured clearances obtained using the seventh TPD exchange-derived indices
      confirm the accuracy of the D/P ratios for creatinine and urea derived from any
      exchange after the fifth (preferably the seventh) of a standardized TPD run in
      estimating peritoneal creatinine and urea clearances. This method could represent
      a simple and accurate means for prescribing TPD and routinely assessing TPD
      delivery.

PMID- 8761546
TI  - Rapid decline of residual renal function in patients on automated peritoneal
      dialysis.
AB  - OBJECTIVE: To determine the effect of peritoneal dialysis modalities such as
      nightly intermittent peritoneal dialysis (NIPD), continuous cyclic peritoneal
      dialysis (CCPD), and continuous ambulatory peritoneal dialysis (CAPD) on residual
      renal function. DESIGN: A six-month prospective, nonrandomized comparison study.
      SETTING: Outpatient CAPD unit of a university hospital. PARTICIPANTS: Eighteen
      end-stage renal disease patients treated by peritoneal dialysis (8 by NIPD, 5 by
      CCPD, and 5 by CAPD). INTERVENTIONS: Samples from the total dialysate, blood, and
      24-hour urine collection were obtained monthly. MEASUREMENTS: Urea, creatinine,
      and beta2-microglobulin concentrations were measured. Renal and peritoneal
      clearances of each substance and KT/V urea were calculated. Residual renal
      function (RRF) was estimated by renal creatinine clearance (RCcr). RESULTS: No
      significant differences in age, sex, and primary renal disease among the three
      groups were noted. In all groups, anemic and hypertensive states were controlled
      identically, and mean weekly total (renal + peritoneal) KT/V urea (over 2.1/wk)
      and total creatinine clearance (over 60 L/wk/1.73 m2) were maintained during the
      whole experimental period. Starting mean RCcr was near 4.0 mL/min/1.73 m2 in all
      groups. Thereafter, a rapid and significant decline in RRF was demonstrated on
      NIPD and CCPD. The declining rates of RCcr values at 6 months after starting NIPD
      and CCPD were -0.29 and -0.34 mL/min/month, respectively, which were much greater
      than those of CAPD (+0.01 mL/min/month). CONCLUSION: Because of a possibly
      characteristic progressive loss of RRF in automated peritoneal dialysis (APD),
      strict regular assessment of RRF should be performed from the start of APD.

PMID- 8761545
TI  - Continuous peritoneal dialysis in heavyweight individuals: urea and creatinine
      clearances.
AB  - OBJECTIVE: To study whether or not continuous peritoneal dialysis (CPD) can
      provide acceptable levels of normalized urea and creatinine clearance in
      heavyweight individuals. DESIGN: Retrospective analysis of urea and creatinine
      clearance studies. SETTING: CPD patients followed in four dialysis units in
      Albuquerque, two dialysis units in Thessaloniki, and two dialysis units in
      Athens. PARTICIPANTS: One hundred and ninety-nine patients on CPD with 266
      clearance determinations between 1991 and 1995. INTERVENTIONS: The heavyweight
      group consisted of 22 patients (24 clearance studies) weighing 100 kg or more
      (109 +/- 8.7 kg) at the time of the clearance study. All subjects were obese. The
      reference group consisted of 177 CPD subjects (242 clearance studies) of normal
      weight (68.7 +/- 12.2 kg). Urea fractional clearance (KT/V) and normalized
      creatinine clearance (Ccr) were compared between the heavyweight and the
      reference groups. MAIN OUTCOME MEASURES: The lowest acceptable weekly levels were
      set at 1.70 for KT/V and 54.4 L/1.73 m2 for Ccr. RESULTS: Weekly KT/V was 1.75 +/
      0.41 in the heavyweight group and 1.94 +/- 0.52 in the reference group (p =
      0.047). Corresponding weekly Ccr levels were 64.0 +/- 24.3 and 77.6 +/- 40.3
      L/1.73 m2, respectively (p = 0.021). In the heavyweight group, 13 studies (54.2%)
      had acceptable KT/V values compared to 160 studies (66.1%) in the reference group
      (NS). Corresponding values for acceptable Ccr were 17 (70.8%) and 165 (68.2%),
      respectively (NS). Drain volume was 12.96 +/- 4.40 L/24 hours in the heavyweight
      group and 9.63 +/- 2.58 L/24 hours in the reference group (p = 0.001). High daily
      exchange volume was delivered by a combination of daily continuous ambulatory
      peritoneal dialysis (CAPD) and nocturnal automated peritoneal dialysis (APD) in
      13/16 heavyweight studies. This combination was tolerated better than any other
      method of delivering a large daily exchange volume. CONCLUSION: Although
      normalized urea and creatinine clearances are lower in obese, heavyweight
      individuals than in lean CPD subjects with lower weight, approximately equal
      percentages of these two groups achieve acceptable clearance levels. However,
      heavyweight individuals require larger-than-usual daily exchange volumes. The
      preferred way to deliver these large dialysate volumes is a combination of daily
      CAPD and nocturnal APD.

PMID- 8761547
TI  - Combination therapy involving ciprofloxacin for peritonitis.

PMID- 8761548
TI  - Use of computerized tomography in the evaluation of a CAPD patient with a foramen
      of Morgagni hernia: a case report.

PMID- 8761550
TI  - A case of Kluyvera cryocrescens peritonitis in a CAPD patient.

PMID- 8761549
TI  - Accuracy or bias in nurses' ratings of patient compliance: a comparison of
      treatment modality.
AB  - OBJECTIVE: The study examined the accuracy of nurses' assessments of patient
      compliance and identified factors influencing these assessments, including
      possible biases. DESIGN: Nurses' assessments of compliance, lab serum levels of
      dietary compliance, and interdialytic weight gain (IWG) were collected and
      compared to each other. End-stage renal disease (ESRD) patients on peritoneal
      dialysis (PD) and hemodialysis (HD) were compared on these measures and their
      compliance. SETTING: The study was conducted at the tertiary care university
      hospital at Stony Brook. PATIENTS: Data were collected for 62 ESRD patients (38
      male, 24 female; mean age 54 years). The sample consisted of 26 HD and 36 PD
      patients. INTERVENTIONS: Nurses rated patients' compliance with fluid
      restrictions (HD patients only) and overall dietary compliance, as well as
      individual indicators of compliance including protein, potassium, and phosphorus
      compliance on a 7-point rating scale. Interdialytic weight gain, dietary (serum
      BUN and K levels), and medication compliance were recorded from charts for a 3
      month period for each patient. MAIN OUTCOME MEASURES: The main outcome measures
      were the correlations between nurses' ratings of compliance and medical
      compliance data and the regression coefficients, which indicate the relative
      importance of each of the factors that nurses use to make their compliance
      ratings. RESULTS: Nurses' ratings for patients in both treatment modalities were
      highly correlated with the medical data for measures of fluid (r = 0.66, p <
      0.001), potassium (r = 0.36, p < 0.01), and phosphorus (r = 0.36, p < 0.01). A
      regression analysis indicates that potassium (beta = 0.48, p < 0.001), phosphorus
      (beta = 0.19, p < 0.05), and protein (beta = 0.31, p < 0.01) all significantly
      contributed to nurses' assessments of patients' overall compliance. However,
      nurses' ratings of education levels for patients in both treatment modalities
      were not associated with phosphorus (r = 0.07, p < 0.61), protein (r = 0.18, p <
      0.23), or potassium (r = 0.03, p < 0.85) measures. Finally, regressions revealed
      that nurses used personal knowledge of the patients when rating noncompliant
      patients (beta = 0.49, p < 0.05) but not when rating compliant patients (beta =
      0.05, p < 0.75). CONCLUSIONS: Nurses rely heavily on medical records to rate
      patients' compliance and to make accurate assessments. Nurses also use several
      individual indicators (lab values and IWG) to rate overall dietary compliance,
      suggesting a thorough assessment. While assessments are not biased by personal
      factors such as nurses' perceptions of patients' education levels, nurses do rely
      on personal knowledge when rating noncompliant patients.

PMID- 8761551
TI  - Giardial peritonitis complicating CAPD.

PMID- 8761552
TI  - Placement and management of PD catheters: experience from Hungary.

PMID- 8761553
TI  - Effectiveness of low-dose, intraperitoneal human gamma globulin in the treatment
      of refractory CAPD peritonitis.

PMID- 8761554
TI  - CAPD catheter malposition during a roller coaster ride.

PMID- 8761555
TI  - Hemoperitoneum after pericardiocentesis in a CAPD patient.

PMID- 8761556
TI  - Flavobacterium group IIb peritonitis in a patient on chronic ambulatory
      peritoneal dialysis.

PMID- 8761557
TI  - Physiological approaches to increase biocompatibility of peritoneal dialysis.

PMID- 8761558
TI  - Serum lipids in black Africans on chronic ambulatory peritoneal dialysis.

PMID- 8761559
TI  - Sexually transmitted diseases in developing countries.

PMID- 8761560
TI  - A successful control programme for falciparum malaria in Xinyang, China.
AB  - This paper describes a large scale control programme for falciparum malaria in
      Xinyang prefecture, China, from the early 1980s to 1992. Falciparum malaria,
      transmitted mainly by Anopheles anthropophagus, was epidemic in Gusi, Huangchuan,
      Shangcheng and Huaibin counties in the prefecture in the early 1980s, 2922 cases
      being reported in 1984. From 1985 to 1992, DDT residual spraying and the use of
      bed nets impregnated with pyrethroid insecticide were introduced for 2
      consecutive years in areas at higher risk of P. falciparum infection, and then
      gradually extended to cover all the endemic areas over a period of 8 years.
      Malaria control was also carried out through the primary health care system in 4
      counties, as had been done since the 1970s. As a result, no falciparum malaria
      case has been found since 1988 in spite of extensive surveillance, and vivax
      malaria has also decreased greatly. Repeated cross-sectional surveys showed that
      A. anthropophagus could not be found in most sites after 2 consecutive years of
      the vector control programme. Vector control was a major factor in the successful
      elimination of falciparum malaria and decreasing the incidence of P. vivax in the
      4 counties.

PMID- 8761561
TI  - Comparative efficacy of house curtains impregnated with permethrin,
      lambdacyhalothrin or bendiocarb against the vector of bancroftian filariasis,
      Culex quinquefasciatus, in Matara, Sri Lanka.

PMID- 8761562
TI  - The epidemiology of malaria in a Karen population on the western border of
      Thailand.
AB  - From November 1991 to November 1992 a prospective, descriptive study of malaria
      epidemiology was conducted in a Karen population on the western border of
      Thailand. Two study groups were selected at random and more than 80% of the
      subjects were followed for one year. In Group 1, comprising 249 schoolchildren
      (aged 4-15 years), daily surveillance for illness was combined with fortnightly
      malaria surveys. These children experienced 1.5 parasitaemic infections per child
      year (95% confidence interval [CI] 1.3-1.7), of which 68% (193/285) were
      symptomatic (Plasmodium falciparum 84%, P. vivax 57%). The estimated pyrogenic
      densities were 1460/microL for P. falciparum and 181/microL for P. vivax. In
      Group 2, comprising subjects of all age from 428 households, malaria was
      diagnosed during two-monthly surveys, at weekly home visits, and otherwise by
      passive case detection. Malaria and splenomegaly prevalence rates were low in all
      age groups (spleen index 2-9%; P. falciparum prevalence rate 1-4%; P. vivax 1
      6%). Group 2 subjects had 1.0 infections per person-year (95% CI 0.9-1.1), most
      of which were symptomatic (312/357; 87%). Malaria infections clustered in
      households. Overall, P. vivax caused 53% and P. falciparum 37% of the infections
      (10% were mixed), but whereas P. vivax was most common in young children, with a
      decline in incidence with increasing age, P. falciparum incidence rates rose with
      age to a peak incidence between 20 and 29 years, although the risk of developing
      a severe malaria decreased with increasing age. There was no death from malaria
      during the study. P. falciparum infections were more common in males, subjects
      with a history of malaria before the study, and in those who had travelled
      outside their village. These findings suggest a higher transmission rate for P.
      vivax than P. falciparum, although adults still suffered symptomatic malaria due
      to both species. The 2 malaria parasites found in this area contribute
      approximately 50% of infections each, but their clinical epidemiology is very
      different.

PMID- 8761563
TI  - Psychodopygus complexus, a new vector of Leishmania braziliensis to humans in
      Para State, Brazil.
AB  - This paper reports the finding of 4 specimens of Psychodopygus complexus,
      captured in the Paragominas region of Para State, Brazil, naturally infected with
      trypanosomatids that were positively identified as Leishmania (Viannia)
      braziliensis. Attention is drawn to the importance of this species as a vector
      since it is highly anthropophilic and has a very extensive geographical
      distribution in the lower Amazon region of Para State south of the Amazon river,
      including the island of Marajo.

PMID- 8761564
TI  - Presumed vectors of leishmaniasis in the principality of Monaco.

PMID- 8761565
TI  - Markers of Loa loa infection in permanent residents of a loiasis endemic area of
      Gabon.
AB  - Different markers of infection were analyzed in 56 permanent residents of a Loa
      loa endemic village in Gabon. The population was divided into those with
      parasitological evidence of L. loa infection and those with no history of loiasis
      over the period of observation (c. 5 years). 26.7% of villagers had L. loa
      microfilariae, 33.9% had an ocular passage of an adult worm, and 17.8% had
      calabar oedema. Several other clinical symptoms were present in both groups of
      individuals, but none was considered to be pathognomonic for L. loa infection.
      Most of the villagers were polyparasitized, with Plasmodium falciparum and
      gastrointestinal parasites being particularly prevalent. Mansonella perstans was
      present in 80% of the villagers and was equally distributed between L. loa
      microfilaraemic and amicrofilaraemic individuals. Eosinophil levels were elevated
      in the whole population, and were not significantly different between the groups
      who were infected and non-infected with L. loa. Polyclonal immunoglobulin (Ig) E
      levels were high in both the Ambinda villagers and in Gambian serum from patients
      infected with M. perstans alone and there was no significant difference between
      the levels of L. loa specific IgG in the Ambinda villagers and the Gambian
      patients. However, the level of L. loa specific IgG4 was elevated in 75.6% of
      amicrofilaraemic individuals and could discriminate between most individuals
      infected with L. loa and those infected with M. perstans, suggesting that this is
      the best determinant of infection status in the absence of L. loa microfilariae.

PMID- 8761566
TI  - Estimation of the fecund life span of Wuchereria bancrofti in an endemic area.
AB  - A stochastic approach appropriate for general use in endemic communities was
      applied to estimate the average yearly instantaneous rate of loss of Wuchereria
      bancrofti microfilaraemia from infected individuals, and gain by uninfected
      individuals, from longitudinal data. This method was shown to give similar
      results (i.e., the rate of loss was independent of age, while the rate of gain
      differed significantly between age classes) to a previously used method based on
      transmision interruption, provided that the intersurvey interval was > 5 years.
      The method was used to estimate the fecund life span of W. bancrofti in an
      endemic area at 5 years. The results suggest that the life span is at the lower
      end of previous estimates.

PMID- 8761567
TI  - HTLV infection in a group of prostitutes and their male sexual clients in Brazil:
      seroprevalence and risk factors.
AB  - Sera from 653 female prostitutes and 153 male sexual clients living in the city
      of Santos, Sao Paulo, Brazil, were tested for the presence of antibodies to human
      T cell lymphotropic virus types I and II. Seroprevalence for HTLV-I in the
      females was 2.8% and in the males 2.0%. Infection by HTLV-II could not be
      demonstrated. Seropositivity to HTLV-I was not associated with intravenous drug
      use, modality of sexual behaviour or a history of sexually transmitted disease.
      Among the prostitutes, the prevalence of anti-HTLV-I antibodies was 3 times
      higher in those with a history of blood transfusion (P = 0.01).

PMID- 8761568
TI  - Circulation of poliovirus among risk groups in Ibadan, Nigeria.
AB  - Faecal samples collected from 114 fully vaccinated pre-school children and 32
      unvaccinated infants in Ibadan, Nigeria, were assayed for poliovirus in Hep-2 and
      RD cell cultures. 8 strains of poliovirus type 1 were isolated from 146 samples-
      3 from 32 unvaccinated children aged less than 40 d and 5 from 114 fully
      vaccinated children aged between 9 and 60 months. Studies using Sabin and wild
      monoclonal antibodies and the polymerase chain reaction confirmed 7 of the 8
      isolates to be of the wild type, a possible source of infection among vaccinated
      children.

PMID- 8761569
TI  - Occurrence of culturable Vibrio cholerae O139 with ctx gene in various components
      of the aquatic environment in Bangladesh.

PMID- 8761570
TI  - Comparison of the polymerase chain reaction with two classical parasitological
      methods for the diagnosis of Chagas disease in an endemic region of north-eastern
      Brazil.
AB  - The sensitivities for Chagas disease diagnosis of haemoculture, xenodiagnosis,
      and polymerase chain reaction (PCR) amplification of Trypanosoma cruzi
      kinetoplast deoxyribonucleic acid (DNA) were compared for 101 patients living in
      an endemic region who were serologically positive for T. cruzi. PCR gave 60
      positive results (59.4%), while a haemoculture was positive in 26 cases (25.7%)
      and xenodiagnosis in 36 (35.6%). Four xenodiagnosis-positive but PCR-negative
      patients were examined in detail. The discrepancies were not due to inhibition of
      the PCR reactions, as the samples were used successfully to amplify a human
      sequence. Nor were they due to a variation in kinetoplast DNA sequences, as the
      kinetoplast DNA of the parasite strains isolated from these patients after
      xenodiagnosis gave rise to the expected product when amplified by the PCR. We
      concluded that no parasite was present in the 5 mL of blood used for PCR, while
      probably a single T. cruzi cell was present in the blood volume ingested by the
      insects during xenodiagnosis (about 3 mL). This suggests that the total blood
      quantity collected for the PCR may be important with patients with low
      parasitaemia.

PMID- 8761571
TI  - Evaluation of the polymerase chain reaction in the diagnosis of cutaneous
      leishmaniasis due to Leishmania major: a comparison with direct microscopy of
      smears and sections from lesions.
AB  - We have compared the sensitivity of the polymerase chain reaction (PCR) as a
      diagnostic tool against conventional microscopical diagnostic techniques in
      patients with cutaneous leishmaniasis from the Sudan. Twenty-eight patients were
      diagnosed according to clinical criteria followed by microscopical examination of
      histological sections and slit or impression smears. The PCR had a sensitivity of
      86% when used alone, and 93% when combined with Southern blotting. In contrast,
      microscopy of histological sections had a sensitivity of 76% and slit and
      impression smears of only 55% and 48%, respectively. The PCR should be considered
      as a valuable and sensitive diagnostic tool in the diagnosis of cutaneous
      leishmaniasis; it has the added advantage of identification of the species of
      Leishmania causing the lesion.

PMID- 8761572
TI  - A polymerase chain reaction assay to determine infection of Aedes polynesiensis
      by Wuchereria bancrofti.
AB  - The sensitivity of a previously described polymerase chain reaction (PCR) assay
      was improved to detect a single mosquito, infected by as few as 1-2 microfilariae
      of Wuchereria bancrofti, among 20-50 uninfected mosquitoes. Wild-caught Aedes
      polynesiensis were used to compare assessment of infection by dissection of
      individuals with the PCR assay of pools of mosquitoes. The PCR assay was at least
      as sensitive as dissection for detection of mosquitoes infected with W.
      bancrofti.

PMID- 8761573
TI  - Rapid diagnosis and determination of duration of viraemia in dengue fever using a
      reverse transcriptase polymerase chain reaction.
AB  - A rapid, simple diagnostic polymerase chain reaction (PCR) method for the
      diagnosis of dengue fever was developed using a pair of consensus oligonucleotide
      primers and validated with laboratory-derived strains of dengue serotypes 1-4 and
      other common flaviviruses. A cluster of 13 patients with clinical dengue fever
      admitted to a single infectious diseases unit over a period of 3 months allowed
      evaluation of this technology. The PCR was positive in all 11 acute dengue cases
      and negative in 2 convalescent cases and 10 febrile patients recently returned
      from the tropics in whom an alternative diagnosis was established. In some of the
      acute cases, viraemia was detected before the development of a diagnostic
      antibody response (indirect immunoglobulin (Ig) G enzyme-linked immunosorbent
      assay (ELISA) and capture IgM ELISA). In patients from whom sequential sera were
      taken, defervescence and recovery from thrombocytopenia coincided with the
      disappearance of dengue ribonucleic acid from the blood. Nucleotide sequencing of
      the PCR products was undertaken in 2 cases (from India and Guyana) and the
      results showed a close match with previously reported serotype 2 sequencies,
      suggesting a potential for use of this region of the genome in epidemiological
      studies.

PMID- 8761575
TI  - Elevated levels of methaemoglobin in Tanzanian children with severe and
      uncomplicated malaria.
AB  - Elevated levels of methaemoglobin, the ferric form of haemoglobin incapable of
      oxygen transport, have been previously found during Plasmodium vivax infections
      and in acidotic infants. We measured methaemoglobin in the following 5 groups of
      children with P. falciparum malaria admitted to Muhimbili Medical Centre, Dar es
      Salaam, Tanzania. (i) Cerebral malaria (CM) with unrousable coma (n = 50),
      including 32 with complete recovery (CMCR) and 18 with death or neurological
      sequelae (CMDS); (ii) malaria with severe anaemia but without severe respiratory
      distress (SA; n = 6); (iii) uncomplicated malaria (UM; n = 37); (iv) asymptomatic
      parasitaemia (AP; n = 5); and (v) healthy controls (HC; n = 34). Mean
      methaemoglobin levels were elevated in all groups with malaria, forming up to
      16.4% of circulating haemoglobin. The degree of methaemoglobinaemia correlated
      with disease severity and severity of anaemia. Mean methaemoglobin levels in
      children with AP, UM, SA, CMCR and CMDS were 3.3%, 4.1%, 5.6%, 4.7% and 5.8%
      respectively; the mean levels in those with clinical disease were significantly
      higher than those in healthy controls (2.0%). Methaemoglobinaemia > 10% was found
      in 5.4%, 16.7%, 12.5%, and 22.2% of those with UM, SA, CMCR and CMDS,
      respectively. In the presence of parasite sequestration, impaired tissue
      perfusion, and a reduction in oxygen carrying capacity of blood due to anaemia, a
      further reduction in oxygen carrying capacity from even a modest concentration of
      methaemoglobin is likely to exacerbate tissue hypoxia, perhaps critically so in a
      minority of anaemic and acidotic patients with severe falciparum malaria.

PMID- 8761574
TI  - Retinal findings predictive of outcome in cerebral malaria.
AB  - The pathogenesis of cerebral malaria is poorly understood. Direct and indirect
      ophthalmoscope examinations of 141 Malawian children with strictly defined
      cerebral malaria revealed 2 distinct and prognostically significant findings:
      papilloedema and extramacular retinal oedema. The relative risk of death in
      patients with papilloedema was 6.7 times that in patients without papilloedema.
      Extramacular retinal oedema was associated with a 2.9 fold increase in the
      relative risk of dying. The mortality rate in patients with neither of these
      signs was only 1.3% compared to an overall mortality rate of 9.2%. The clinical
      and laboratory features associated with each of these ophthalmological findings
      were different, suggesting that there may be at least 2 different pathogenetic
      processes in patients with cerebral malaria.

PMID- 8761576
TI  - Epileptic seizures and malaria in Kenyan children.
AB  - Between October 1990 and November 1991 data were collected on the frequency,
      causes, and nature of epileptic seizures in children admitted to the paediatric
      ward at Kilifi District Hospital, Kenya, from a defined study area. During this
      period, 1324 children were studied, of whom 15.8% had seizures as part of their
      illness. Malaria was by far the commonest cause of seizures, accounting for
      69.0%; no other single condition caused more than 4.4%. The proportion of
      respiratory infections complicated by seizures was 4.0% compared to 31.3% for
      malaria. Only 25% of malaria-related epileptic seizures were associated with
      cerebral malaria; the remainder were associated with otherwise uncomplicated
      malaria and, in this group, 84% had complex seizures, with 47% being partial and
      over 70% repetitive. There was no relationship with fever, with 54% of observed
      seizures occurring at rectal temperatures below 38 degrees C. The minimum
      community incidence of complex seizures in association with non-cerebral malaria
      was 5.8 per 1000 per year. Complex epileptic seizures in association with
      otherwise uncomplicated malaria are common and may be a significant cause of
      longer term morbidity in malaria endemic areas.

PMID- 8761577
TI  - The effects of deworming on indicators of school performance in Guatemala.
AB  - Intestinal helminths are among the most common infections in school-age children.
      Of 246 children, aged 7-12 years, attending school in rural Guatemala, 91%
      carried Ascaris lumbricoides and 82% carried Trichuris trichiura. These children
      were randomly assigned to receive either albendazole or placebo at 0 and 12 weeks
      in a 'double-blind' study of the effects of deworming on indicators of school
      performance. Albendazole successfully rid the children of Ascaris but it was less
      effective against Trichuris. The children's performance in tests of reading and
      vocabulary were measured at 0 and 24 weeks, the Peabody picture vocabulary test
      was given at 24 weeks, and attendance was measured throughout the school year.
      Comparison of the treated and placebo groups showed no positive effect of
      deworming. The treated children were largely free of Ascaris for at least 6
      months, but during that period we could not detect any improvement in reading,
      vocabulary, or attendance. The effects of being Trichuris-free were not examined
      because of the limited effectiveness of albendazole against this worm at the
      dosage used.

PMID- 8761578
TI  - Nutritional status and weight gain in patients with pulmonary tuberculosis in
      Tanzania.
AB  - We assessed nutritional status in 200 adult Tanzanian patients with smear
      positive pulmonary tuberculosis before, during, and after 6 months of
      tuberculosis treatment; 148 patients (74%) were successfully followed for 12
      months. Marked nutritional impairment was present on admission: 77% of males and
      58% of females had a body mass index (BMI) below 18.5; approximately one-fifth
      had BMI < 16.0. The length of hospital stay and gender, rather than
      microbiological response, were the major determinants of weight gain during
      treatment. Patients infected with human immunodeficiency virus (HIV) gained more
      weight than uninfected patients. Most patients lost weight after completing
      treatment and returning home. At 12 months, 32% of male and 19% of female
      patients considered cured of tuberculosis had BMI < 18.5. It is concluded that
      patients with tuberculosis from this area of Tanzania frequently have evidence of
      malnutrition both before and after treatment for tuberculosis. Weight gain during
      therapy appeared to be an unreliable indicator of overall treatment response.
      However, the results also demonstrated that nutritional rehabilitation can be
      successfully achieved even in HIV-positive tuberculosis patients and in patients
      with a suboptimal response to therapy.

PMID- 8761579
TI  - Raised levels of agalactosyl IgG in childhood tuberculosis.
AB  - Raised levels of agalactosyl immunoglobulin G (IgG) have been found in adults
      with tuberculosis, Crohn's disease and rheumatoid arthritis, and recent evidence,
      both circumstantial and experimental, suggests that it has distinct functional
      properties that play a role in pathogenesis. Since tuberculosis in infants is
      strikingly different from the disease seen in adults, but switches to the adult
      form at adrenarche or puberty, we documented the association of agalactosyl IgG
      with tuberculosis in childhood between the ages of 0 and 16 years. Sera were
      collected from 99 children diagnosed as cases of tuberculosis in Istanbul,
      Turkey, and compared with levels in non-tuberculous controls. The percentage of
      agalactosyl IgG was significantly raised in children with tuberculosis overall (P
      < 0.001, Mann-Whitney U test) and in all age groups except for children over 12
      years old, whose numbers were too small to be meaningful. Therefore the
      differences between adult and childhood tuberculosis are not due to a difference
      in the tendency for agalactosyl IgG to be produced at different ages. The
      percentage of agalactosyl IgG may be useful for monitoring the progress of
      individual complicated cases.

PMID- 8761580
TI  - Urinary NAG as an early indicator of renal damage in Russell's viper bite
      envenomation.
AB  - Urinary N-acetyl-beta-D-glucosaminidase (NAG; beta-N-acetylglucosaminidase; EC
      3.2.1.30), blood urea, serum creatinine and creatinine clearance were measured in
      23 patients bitten by Russell's viper (Daboia russelii siamensis), with systemic
      envenomation, at different time intervals after the bite during clinical
      observation for 5 d. Activities of urinary NAG were compared with these
      indicators of renal function in 3 clinical conditions: non-oliguric acute renal
      failure (ARF), oliguric ARF not requiring peritoneal dialysis, and oliguric ARF
      requiring peritoneal dialysis. Cut-off values to identify the 3 conditions were
      established. When the times of onset of the conditions, indicated by the cut-off
      values, were compared, urinary NAG was generally found to be the earliest
      indicator of renal damage. In each type of ARF, the urinary NAG level was
      abnormal before changes in the values of the other indicators of renal function.
      It may be possible to predict the types of ARF within 2 h after the bite by
      measurement of urinary NAG.

PMID- 8761581
TI  - Diminished delayed hypersensitivity responses in the legs and feet of patients
      with endemic Kaposi's sarcoma.

PMID- 8761582
TI  - Reducing the oral quinine-quinidine-cinchonin (Quinimax) treatment of
      uncomplicated malaria to three days does not increase the recurrence of attacks
      among children living in a highly endemic area of Senegal.
AB  - A 3 d shortened course of the quinine-quinidine-cinchonin association Quinimax
      was compared to the usual 7 d regimen for routinely treating 462 acute
      uncomplicated Plasmodium falciparum malaria attacks in 72 children under the age
      of 10 years in Dielmo, a holoendemic village in Senegal. 25 mg/kg Quinimax salt
      daily, given in 3 equal doses, improved clinical status in 99.6% of the patients
      receiving the course and in all of those treated for 7 d. Even if the 3 d course
      did not systematically eliminate parasitaemia, reducing oral Quinimax treatment
      of uncomplicated malaria from 7 to 3 d did not increase the recurrence of
      attacks, even among the youngest children. Both the quinine sensitivity of the
      Senegalese strains of P. falciparum and the partial acquired immunity of the
      children were probably responsible for the absence of any difference between the
      courses. Oral Quinimax for 3 d is a possible alternative regimen to chloroquine
      and sulfadoxine-pyrimethamine for treating uncomplicated malaria in highly
      endemic areas of Africa where clinical resistance to these drugs exists.

PMID- 8761583
TI  - High level of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine in
      children in Tanzania.
AB  - In many areas of tropical Africa affected by chloroquine-resistant Plasmodium
      falciparum, a combination of sulfadoxine and pyrimethamine (S-P) is used for
      alternative medication, especially in young children. In Magoda village in Muheza
      District, north-eastern Tanzania, 38 children 1-10 years of age were enrolled in
      a therapeutic study of S-P in July 1994. All had monoinfections of P. falciparum
      and an asexual parasite count of 1000-80,000/microL of blood. S-P was given as a
      single dose corresponding to 0.8-1.4 mg pyrimethamine/kg body weight. Of the 38
      children followed up to day 7, 10 showed an S/RI response, 26 an RII response,
      and 2 an RIII response. Older children had lower pre-treatment parasitaemia and a
      better therapeutic response than younger children. Among the various contributory
      factors responsible for the poor therapeutic result, drug pressure from a
      prophylactic intervention with weekly dapsone-pyrimethamine between May 1993 and
      May 1994 seems to have been the most important.

PMID- 8761584
TI  - Association between antifol resistance in vitro and DHFR gene point mutation in
      Plasmodium falciparum isolates.

PMID- 8761585
TI  - Relapses following treatment of early-stage Trypanosoma brucei gambiense sleeping
      sickness with a combination of pentamidine and suramin.
AB  - 616 patients with early Trypanosoma brucei gambiense trypanosomiasis (no
      trypanosomes in the cerebrospinal fluid [CSF] and a CSF white cell count [WCC] of
      1-5/mm3) were treated with a combination of pentamidine (6 intramuscular [i.m.]
      injections of 4 mg/kg) and suramin (2 intravenous [i.v.] injections of 20 mg/kg)
      in Nioki hospital, Zaire, between 1983 and 1992; 46 (7.5%) of them subsequently
      relapsed. There was no increase in the frequency of treatment failure during this
      10 years' period. Relapses were more frequent in children aged 0-17 years (19/163
      [11.7%]) than in adults (26/420 [6.2%] (relative risk [RR] = 1.88, 95% confidence
      interval [CI] 1.07-3.31, P = 0.04). Even within this small range of CSF WCC, the
      risk of treatment failure increased in parallel with the WCC count and reached
      10/36 (27.8%) in patients with a CSF WCC of 5/mm3. Treatment failures were more
      frequent (5/30 [16.7%]) in a small group of patients treated with a combination
      of diminazene (3 i.m. injections of 7 mg/kg) and suramin (one i.v. injection of
      20 mg/kg) than in the pentamidine/suramin group (RR = 2.23, 95% CI 0.96-5.21, P =
      0.08). Our data support the view that central nervous system involvement occurs
      early in Gambian trypanosomiasis, which in turn raises doubts about the
      usefulness of adding suramin to pentamidine, as the former drug, which is more
      expensive than pentamidine and has to be administered intravenously, penetrates
      poorly into the CSF and may potentially decrease free pentamidine levels in blood
      and CSF.

PMID- 8761586
TI  - Failure of a combination of two antifungal drugs, terbinafine plus itraconazole,
      in Sudanese post kala-azar dermal leishmaniasis.

PMID- 8761587
TI  - Rapid in vitro test for determination of anti-amoebic activity.
AB  - A rapid microplate assay for the detection of potential compounds active against
      Entamoeba histolytica is described. The assay is based on the metabolic reduction
      of a tetrazolium salt by E. histolytica trophozoites as an indicator of their
      viability which may be measured photometrically. The method was validated by
      determining the dose-response characteristics of standard amoebicides and
      correlating optical density and cell number; it provides a convenient means of
      selecting potentially novel anti-amoebic compounds for subsequent testing in
      vivo.

PMID- 8761588
TI  - Histological evidence for adulticidal effect of low doses of diethylcarbamazine
      in bancroftian filariasis.
AB  - The ability of diethylcarbamazine (DEC) to kill adult Wuchereria bancrofti worms
      was evaluated by examining lymphatic nodules formed after treatment with 4
      different treatment schedules of 193 males living in the endemic area of Greater
      Recife, Brazil. Lymphatic nodules appeared in the spermatic cord or upper
      extremities in 43 of 138 microfilaraemic individuals, in 3 of 30 amicrofilaraemic
      patients with filarial disease manifestations, and in 1 of 25 asymptomatic
      amicrofilaraemic residents of the endemic area treated with DEC. Fourteen of
      these nodules were surgically removed 10-150 d after the start of treatment.
      Regardless of the DEC dosage and schedule used, all nodules contained damaged and
      degenerating adult worms. An exuberant granulomatous process with large numbers
      of eosinophils and progressive fibrosis gradually developed around the dead
      parasites. The mechanism(s) by which DEC killed adult W. bancrofti could not be
      determined.

PMID- 8761589
TI  - Anti-Pfs25 monoclonal antibody 32F81 blocks transmission from Plasmodium
      falciparum gametocyte carriers in Cameroon.

PMID- 8761590
TI  - A filter paper technique for the detection of anti-filarial IgG4 in lymphatic
      filariasis.
AB  - In a previous study performed in south Sulawesi (Sulawesi Selatan), Indonesia, we
      established that the immunoglobulin G4 (IgG4) enzyme-linked immunosorbent assay
      (ELISA) is a suitable community diagnostic method and that it can distinguish
      areas of high and low prevalences within short distances. In an attempt to make
      this diagnostic tool more applicable in the field, a comparative study using
      serum and blood collected on filter paper was undertaken with 568 individuals
      living in 2 areas with different endemicity for brugian filariasis in south
      Sulawesi. In Mamuju district, where the microfilaria (mf) prevalence of the
      studied individuals was 18.4%, antifilarial IgG4 was present in 73.1% of the
      venepuncture samples and 72.5% of the filter paper samples, respectively. In
      Mangkutane district, where lymphatic filariasis is transmitted at a low level (mf
      rate 2.4%), antifilarial IgG4 was detected in 35.5% and 39.9% of similar samples,
      respectively. There was no significant difference in the IgG4 detection rate
      determined from venepuncture and filter paper samples from the same donors (P =
      0.124), and the IgG4 values were highly correlated (p = 0.97, P < 0.001, n =
      568). These results indicate that the filter paper technique for collection of
      blood samples is a suitable alternative to venepuncture for use in the IgG4
      ELISA.

PMID- 8761591
TI  - Cytokine secretion in vivo and ex vivo following chemotherapy of Mycobacterium
      tuberculosis infection.
AB  - The human immune response to tuberculosis is partly mediated by the
      proinflammatory cytokines tumour necrosis factor (TNF), interleukin (IL)-6, and
      IL-8. We investigated plasma concentrations of these cytokines before and after
      maximal lipopolysaccharide stimulation ex vivo of whole blood leucocytes from
      Zambian patients. 32 patients with non-fatal tuberculosis, 25 of whom were
      seropositive for human immunodeficiency virus (HIV), were followed for 9 months.
      Patients were assessed at presentation to hospital (visit A), after 2 months'
      antimycobacterial therapy (visit B), and when chemotherapy was completed (visit
      C). Between visits A and B, patients regained weight (P = 0.03) and became less
      anaemic (P = 0.0001). At visit B, haemoglobin concentration remained lower in HIV
      seropositive patients (P = 0.001) and the erythrocyte sedimentation rate (ESR),
      initially elevated in all patients, was higher in HIV seropositive patients (100
      +/- 6 mm vs. 43 +/- 11 mm in 1 h in seronegative patients; P = 0.002). Plasma IL
      8 concentrations were increased at visit C as was IL-8 secretion ex vivo (P <
      0.0001 at all time points). Otherwise plasma cytokine levels and secretion ex
      vivo remained similar throughout the study. Concurrent HIV infection resulted in
      persistently decreased IL-6 secretions ex vivo although ESR remained high. In
      summary, after antibiotic therapy in vivo IL-8 secretion ex vivo increased, which
      supports other data suggesting that IL-8 has a role in immunity to tuberculosis.

PMID- 8761593
TI  - Criterion for inclusion in onchocerciasis control programmes.

PMID- 8761592
TI  - Random amplified polymorphic DNA for the differentiation of Leishmania donovani
      isolates from Sudan.

PMID- 8761594
TI  - [Specificities of antibacterial activity of zwitterionic 7-methoxyimino cephems
      (cephalosporins of fourth generation].
AB  - Zwitterionic 7-methoxyimino cephalosporins possess a variable substitution at C3
      which contains a quaternary nitrogen. These cephalosporins display low affinities
      for class I beta-lactamase and rapid penetration through the outer membrane of
      Gram negative bacilli. Hence, they remain active against some, but not all,
      ceftazidime-resistant Enterobacteriaceae. Antipseudomonas activities are
      generally similar to that of ceftazidime except that cefelidin is more active.
      The new zwitterionic compounds express greater antistaphylococcal potency than
      does ceftazidime. On the basis of structural and antibacterial characteristics
      the expression "forth generation" is acceptable to describe the wzitterionic 7
      methoxyimino cephalosporins.

PMID- 8761595
TI  - [Bacterial resistance and management of nosocomial infections: relations to
      hematology].
AB  - Because they receive many infected patients with various degrees of
      immunosuppression, the haematology departments have a high consumption of
      antibiotics. The possible relationship between antibiotic consumption and
      bacterial resistance is discussed in many specialities, especially for some
      classes like quinolones. This possible relationship has to be evocated in
      haematology where patients are at high risk of severe sepsis because of
      neutropenia. In Henri Mondor hospital, we studied the evolution of bacterial
      susceptibility and of antibiotic consumption in the haematology unit on a 6 year
      period. We found that this susceptibility was finally stable over time. The main
      factors which may influence the evolution of the bacterial susceptibility in our
      study, and in the literature are discussed.

PMID- 8761596
TI  - [Bacteria, multiresistant to antibiotics, in intensive care units:
      epidemiological context and strategies of control].
AB  - In France, many hospitals have reported high prevalence of multiply resistant
      strains, mostly in intensive care units. However, resistance has spred to other
      medical or surgical wards, and to rehabilitation or long term care facilities as
      well. Both antibiotic misure and cross-colonization via tronsient carriage on
      bouds of caregivers account for these epidemics. In turn, high prevalence of
      resistance leads to increased antibiotic prescriting which results in extra costs
      and further emergence of new resistance mechanisms. In addition, such high
      prevalence might well contribute to increased morbidity and extra-incidence of
      nosocomial infections. Control of resistant strains requires proper use of
      antibiotics and prevention of cross-colonization, which relies on identification
      of reservoirs and effective implementation of isolation precautions.

PMID- 8761597
TI  - Usefulness of a computerized expert system associated with systematic O
      serotyping for the early detection of outbreaks of hospital acquired infections
      and for the presumptive antibiotic therapy of Pseudomonas aeruginosa infections.
AB  - Over a four-year period, the systematic O-serotyping of all Pseudomonas
      aeruginosa isolated in Hopital de Rodez associated with the use of a computerized
      expert system, facilitated the early detection of two outbreaks of nosocomial
      infections with multiresistant serotype O:11 and multiresistant serotype O:12 P.
      aeruginosa respectively involving ten patients over 16 months and six patients
      over six months. Over this four-year period, serotype O:12 represented 14% of 404
      clinical isolates of P. aeruginosa, and most isolates of this serotype were
      resistant to multiple antibiotics. Combination experiments showed that
      fosfomycin/amikacin together were active against 86% of O:12 isolates.
      Fosfomycin/amikacin might be considered as a therapeutic alternative to
      ceftazime/amikacin for the presumptive antipseudomonal therapy of serotype O:12
      infections.

PMID- 8761598
TI  - [In vitro study of antibacterial activity of cefepime (Axepim) against gram
      negative bacteria: comparison with cephalosporins and other beta-lactams].
AB  - The susceptibility to cefepime and to other beta-lactams of 1017 inducible
      cephalosporinase-producing enterobacteria, 897 Pseudomonas aeruginosa strains,
      and 295 Acinetobacter baumanii strains was studied over a two-year period (July
      1, 1993 to June 30, 1995). The isolates were from patients in visceral surgery,
      intensive care, and clinical hematology wards. Cefepime was compared to other
      third-generation cephalosporins and to imipenem, aztreonam, and the piperacillin
      tazobactam combination. Cefepime was more active than the other cephalosporins
      against Enterobacter cloacae, Serratia marcescens and Citrobacter freundii.
      Activity of cefepime on the study isolates was also greater than that of
      aztreonam and of the piperacillin-tazobactam combination. Cefepime exhibited
      outstanding activity against Pseudomonas aeruginosa strains except those with the
      O12 serotype.

PMID- 8761599
TI  - [Practical use of cefepime in an University hospital. Retrospective study of 35
      cases].
AB  - The authors report a retrospective study of 35 patients treated with cefepime
      (Axepim). This patients were either hospitalized in a medical or in a surgical
      ICU or were febrile neutropenic patients. The non neutropenic group was put on
      cefepime for nosocomial pneumonia or miscellaneous sepsis. When recovered,
      Enterobacteriaceae were the most frequent pathogens. Clinical cure rate for the
      patients treated with cefepime was 83%. Cefepime is a safe and effective
      empirical treatment for serious infections and nosocomial infections in
      particular.

PMID- 8761600
TI  - [New modalities of administration of amikacin: economic point of view of a
      hospital pharmacist].
AB  - Once daily amikacin dosing schedule rather divided doses every 8 or 12 hours has
      the potential to provide a more convenient dosing interval, reduced pharmacy and
      nursing time for preparation and administration. In a 700 beds hospital we have
      estimated that once daily amikacin dosing can provide an annual cost saving
      ranging from 17000 french francs (ff) when the drug is administered with an
      electric syringe to 70000 ff when a flow regulator is used to control the
      infusion rate. The amikacin once daily dosing requires a projected 430 hours less
      nursing time per year.

PMID- 8761601
TI  - [Analyses of rhythms of the body temperature in free running in rats].
AB  - We have previously observed a light-induced suppression of circadian rhythms of
      body temperature and locomotor activity in 50/55 male Sprague Dawley rats (Am. J.
      Physiol., 1995). This study presents a description of 4 records of body
      temperature obtained by telemetry and compares three methods of period analysis
      (Fourier analysis, autocorrelation and cosinor). In case of persistant circadian
      rhythms, Fourier analysis and cosinor method agree and allow description of
      rhythm parameters. However, in case of an alteration of the circadian system in
      continuous light, these 2 methods can disagree on the dominant period.
      Autocorrelation analysis permits to conclude on the absence of circadian and
      ultradian rhythmicity. These results demonstrate the necessity to associate
      several methods for period analysis and plaids for the development of a strategy
      for data processing of longitudinal time series.

PMID- 8761602
TI  - [Study of control of the production of melatonin by perifusion of pineal bodies
      in rats].
AB  - We have documented the kinetic characteristics of melatonin production in
      perifused pineals removed from rats sacrified at 6 circadian stages (L:D = 12:12)
      i.e. 3, 7, 11, 15, 19, 23 hours after light onset (HALO). The initial melatonin
      production levels were as expected higher in glands removed during the dark than
      in those removed during the light. The higher the initial level was, the more
      rapide it decreased. Whatever the circadian stage the melatonin production
      decreased during the first 3-4 hours, then remained fairly constant up to 8 hours
      of perifusion. The perifusion of rat pineal glands removed at different times of
      the light-dark cycle showed a greater, beta-adrenergic-stimulated production of
      melatonin in glands obtained at the beginning of either the light or the dark
      stage. The effect of isoproterenol was found dependent upon its enantiomeric
      forms (-, +/-, +). The relative order of potency was (-) > (+/-) > (+)
      enantiomer. These results show that the response of pineal beta-adrenergic
      receptors to isoproterenol is stereospecific this response is also circadian
      stage dependent.

PMID- 8761603
TI  - [Study of circadian rhythms of activity by actometry: preliminary results in 30
      patients with metastatic colorectal cancer].
AB  - Activity circadian rhythms were measured non-invasively in 30 patients with
      metastatic colorectal cancer by wrist actigraphy, and compared with control data.
      Patients and control subjects were requested to wear the actigraph at home for 2
      to 5 days. Control time-series exhibit high activity levels (150 to 350
      counts/min) during daytime, followed by low activity levels (0 to 50 counts/min)
      during the night. In patients, the contrast between daytime activity and
      nocturnal sleep is noticeably less marked, and a wide inter-patient variability
      can be observed. This alteration of the rest-activity rhythm in the cancer group
      was statistically validated by autocorrelation test. Results from the cosinor and
      he maximal entropy spectral analysis must be interpreted more cautiously, since
      the prerequisites for these tests may not be fulfilled by actometric time-series.
      These results indicate that cancer patients may have altered rest-activity
      circadian rhythms. The significance and prognostic value of such alterations
      deserve further testing in a larger population. Actigraphy may provide a simple
      and innovative tool to study the circadian system in cancer patients.

PMID- 8761604
TI  - [Control of cell proliferation: towards new strategies suggested by modelling the
      mitotic oscillator].
AB  - The eukaryotic cell division cycle is governed by a biochemical oscillator
      controlling the periodic onset of mitosis. This oscillator involves a
      phosphorylation-dephosphorylation cascade that requires the synthesis of cyclin
      and results in the periodic activation of the cdc2 protein kinase. A minimal
      cascade model involving cyclin and cdc2 kinase accounts for the occurrence of
      sustained oscillations. The oscillations occur in a precise domain of parameter
      values; outside this domain, the cascade evolves towards a stable steady state
      corresponding to cellular quiescence. The model suggests different ways to stop
      the mitotic oscillator and, thereby, to control cell proliferation. Arrest of the
      mitotic oscillator may occur upon inhibiting or activating the enzymes of the
      cascade beyond critical values that define the boundary between the absence or
      presence of sustained oscillations.

PMID- 8761605
TI  - [Rhythmic component of twelve hours].
AB  - From observations made on the rhythms in different systems: changes in plasmatic
      concentrations of 5-fluorouracil administered at a constant rate, proliferative
      activity of human tissues (bone marrow and oral mucosa), actometry, variations of
      glutathione levels in the liver and kidney from ice, we show the existence of a
      12 hours rhythmic component and we discuss the putative importance of this
      component.

PMID- 8761606
TI  - [Analysis by computer simulation of cell kinetics of the liver].
AB  - A computer simulation model of cell kinetics is established to represent the
      variations of rat hepatocyte populations in several circumstances: normal growth,
      circadian rythms, response to partial hepatectomy under different conditions.
      This model differs from usual mathematical models-sets of equations--by the use
      of digital simulation techniques. Each cell in the population is represented by a
      set of variables in the computer memory. When experiments are simulated, the
      values of these variables are modified step by step according to the hypotheses
      we want to test. Counts and statistics derived at each step from the simulation
      are then compared to experimental values, in order to assess the validity of our
      hypotheses. This procedure enables us to establish a minimal set of conditions
      and outside causal effects necessary to mimic the behaviour of the liver under
      experimental situations similar to those we simulate. Such modelisation suggests
      further work on the mechanisms governing cell kinetics in the normal liver and
      during cancerisation.

PMID- 8761607
TI  - [Circadian changes in physiological urinary excretion of glycosaminoglycans in
      healthy rats].
AB  - Particular chemical structure and original molecular arrangement make the
      glomerular basement membrane (GBM) to play a key role in the glomerular
      filtration, by restraining selectively the transglomerular pathway of high
      molecular weight charged macromolecules. The present study gives evidence, for
      the first time in the literature, of circadian changes in physiological urinary
      glycosaminoglycans (GAGs) excretion, main components of the GBM, in normal rats.
      Urine was collected every 4 hours during 6 consecutive spans in 45 Sprague-Dawley
      rats, housed in individual metabolism cages (8.00-12.00, 12.00-16.00, 16.00
      20.00, 20.00-00.00, 00.00-04.00 and 04.00-08.00). GAGs, water, protein and
      electrolyte excretion were quantified in each sample. The analysis of these
      solute temporal changes was done by the cosinor method and shows that a circadian
      rhythm can be detected. These rhythms exhibit a significant increase between
      20.00 and 8.00, with a peak between 00.00 and 04.00 and a minimum between 12.00
      and 20.00. A precise estimation of the rhythmic characteristics permitted to
      detect the acrophase of each parameter nearly at the same time, respectively at
      23.25 for diuresis, 23.33 for GAGs, 23.32 for proteins, 23.32 for sodium and
      23.44 for potassium excretion. Such chronophysiological data suggest a tight
      correlation between urinary GAGs excretion and urinary water and electrolyte
      excretion in physiological conditions, in normal rats. Because of the great
      complexicity of the factors involved in the kidney the renal excretion
      regulation, the different origins of these temporal changes are largely
      discussed.

PMID- 8761608
TI  - Non-invasive blood pressure monitoring in man.
AB  - Non-invasive, ambulatory, blood pressure monitoring is now widely used for
      research and clinical purpose. Its main advantages over the traditional
      sphygmomanometric method pertain to its ability in providing measures of
      centrality, but also variability, 24-h profile, and excess over selected limits
      (load) of BP in the individual subject. Placebo and "white-coat" effects are much
      less evident when this monitoring technique is used. However, standardization of
      the procedures, choice of methods of data analysis, definition of normalcy, and
      particularly prognostic value are still a matter of discussion. Hence, blood
      pressure monitoring cannot be used as a routine diagnostic technique, except in
      selected clinical situation of proven advantage over the traditional
      sphygmomanometric method.

PMID- 8761609
TI  - [The problematic cosinor].
AB  - We set off the severe deficiences of the simple cosinor method. It doesn't take
      error's correlation and sampling conditions into consideration. Consequently, the
      obtained statistical results are often misleading. This method, exclusively used
      by chronobiologists, should generally be avoided. References are given,
      containing information on adequate data processing [7, 13, 18].

PMID- 8761610
TI  - Circadian rhythm adjustment: difficulties in assessment caused by masking.
AB  - Measured circadian rhythms consist of endogenous (clock-driven) and exogenous
      (lifestyle-driven) components. The exogenous components cause difficulties of
      interpretation of phase and amplitude information. Such effects can be removed by
      "constant routines", but these protocols are restricted to the laboratory. By
      contrast, the process of "purification" of circadian rhythms uses the knowledge
      of an individual's normal lifestyle to separate a measured rhythm into its two
      components. This method has been shown to be practicable in a variety of
      circumstances and to provide a feasible alternative to constant routines.

PMID- 8761611
TI  - [Use of biodegradable microspheres in experimental anticancer therapy.
      Chronopharmacological application].
AB  - We describe the initial experimentations which show that is possible to
      chronomodulate the cisplatin liberation out of some microspheres. The goal is to
      generate, inside one tumeur embolished by those cisplatin loaded microspheres,
      some concentration peaks at the best tolerance time. The cancer is than more hit,
      by the high local anticancer drug concentration, and doses chronomodulations
      preserve the patient by following his tolerance. The experimentation on cancerous
      mice show that this technique could lead to great survival increases. Such a
      protocol might usefuly improve the anticancer therapy.

PMID- 8761612
TI  - [Chronotolerance of corticosterone on DNA synthesis in young growing rats].
AB  - Plasma corticosterone and DNA synthesis were measured during 2 circadian periodes
      following the 25th day of rats. Corticosterone (5 mg/kg) injected at 05 h (1 h
      before the normal corticosterone bathyphase) inhibits and dissynchronizes the
      nycthemeral evolution of the two parameters during the two subsequent periods.
      The same corticosterone administration injected at 17 h (1 h before the normal
      corticosterone acrophase) inhibits the first DNA synthesis wave but both
      parameters are nycthemerally restored from the second period. In this last case,
      the area under the second DNA curve compensates the inhibition of the first wave.
      The results are discussed in the view of chronocorticotherapy recommended in
      patients.

PMID- 8761613
TI  - [Treatment of bacterial pneumonias with cefuroxime-axetil. Predictive value of
      measurement of the in vitro susceptibility].
AB  - Cefuroxime axetil is an oral cephalosporin with proven efficacy in adult lower
      respiratory tract infections. Indeed, it has a broad spectrum of activity in
      vitro, covering most pathogens isolated in this setting and showing good
      stability in the presence of betalactamases. In vitro susceptibility data are a
      major element in the choice of antimicrobial agent. The aim of this study was to
      determine the predictive value of the cefuroxime minimal inhibitory concentration
      (MIC) on the clinical outcome of infections treated with cefuroxime axetil. One
      hundred-and-seventeen (117) patients with radiologically confirmed community
      acquired pneumonia of presumed bacterial origin were enrolled in a prospective
      multicenter trial of cefuroxime axetil therapy (500 mg twice daily). The pathogen
      was identified in 44 patients who were treated for a mean of 8.8 days. Most
      isolates were S. pneumoniae (65.9%) and H. influenzae (15.9%). The MIC was known
      for 35 isolates and was < or = 4 micrograms/ml in 30 cases (85.7%). The MIC value
      was a good predictor of clinical efficacy with a sensitivity of 100%, a
      specificity of 83% and a positive predictive value of 97%; the latter value
      indicates that therapeutic success is virtually certain when the bacterium
      causing pneumonia is susceptible to cefuroxime.

PMID- 8761614
TI  - [Cortical pathways controlling saccades and preparing movements].

PMID- 8761615
TI  - [Prognosis of gliomas].
AB  - In a given patient harbouring a glioma, prognosis is simply a question of
      survival duration rather than projecting the course of illness. The marked
      variability among glioma patients is due to prognosis factors. That are currently
      divided into four broad categories: characteristics of the host, characteristics
      of the tumor, factors related to the influence of the tumor on the host and
      factors related to treatment. For astrocytomas the three factors most closely
      related to duration of survival are age, functional status and histological
      grading. Age is fundamental because it underlies histological grade, functional
      status, accessibility for treatment and therapeutical responses Histological
      grading can now be evaluated with features actually correlated with duration of
      survival. Clinical examination should be recorded using functional scales that
      more precisely reflect the influence of the tumor on the host than simple
      clinical signs. Morphological data provided by neuroradiology, such as correct
      localization or existence of a mass effect provide supplementary prognosis
      factors. The identification, knowledge and quantification of prognostic factors
      and their influence are important and useful for understanding the natural
      history of the disease, to predict the expected survival for individual patient
      and to evaluate the beneficial effects of treatments. In spite of much work
      dealing with gliomas, several questions remain to be answered. The role of
      treatments in grade II astrocytomas is, for example, matter of debate. In
      malignant gliomas, surgical resection could improve the quality of survival,
      radiation therapy the duration of survival and chemotherapy the rate of survivors
      at one and two years. However, many questions are still unanswered. The utility
      of data from the literature is limited, partly due to flaws in the application of
      statistical methods, and partly to wide differences in histological and clinical
      selection criteria. Progress in the field of glioma prognosis is more likely to
      emerge from purely biological tumor research than from clinical studies.

PMID- 8761616
TI  - [Levodopa+selegiline combination and increase of risk of mortality in the
      treatment of Parkinson disease].

PMID- 8761617
TI  - [Nerve transplantation in the central nervous system: a strategy for inducing
      nerve fiber regeneration in lesions of the brain and spinal cord].
AB  - Nerve grafts have long been used as a reconstructive strategy in the human
      peripheral nervous system. In the nervous system (brain and spinal cord),
      peripheral nerve grafts have been used experimentally for promoting axonal
      regeneration in lesioned pathways. Peripheral nerve grafts play the role of
      physical and trophic supports that are favourable for the regeneration of central
      fibres that normally present only abortive regeneration in adult mammals. On the
      basis of several experimental models (axonal regeneration of retinal ganglion
      cells, respiratory neurones, ...) it has now been established that central fibres
      that have regenerated within the nerve grafts retain their ability to transmit
      normal nervous information and can make functional synaptic contact with a
      target. If such a strategy is not yet used in man, it nevertheless constitutes a
      promising approach for the investigation of the central nervous system
      plasticity, and could be useful in the treatment of spinal cord injuries.

PMID- 8761618
TI  - [Reflex epilepsy with seizures induced by mental calculation, playing chess and
      scrabble].
AB  - Reflex seizures induced by higher mental activity is rare. We report the case of
      a young man with myoclonic jerks and generalized tonico-clonic convulsion
      precipitated by calculation, playing chess and scrabble. Routine EEG, including
      hyperventilation and photic stimulation, showed no abnormality. Tests stimulation
      procedures, including spatial tasks, induced focal and generalized EEG spike-wave
      complex and myoclonic jerks. Valproate was effective in reducing epileptic
      seizures during a follow-up period of three years. Comparison of our case with
      previously reported reflex epilepsy with seizures induced by higher mental
      activity is discussed.

PMID- 8761619
TI  - [Unilateral asterixis and focal brain lesions. 12 cases].
AB  - Asterixis is a involuntary movement with spontaneous interruptions and
      intermittent muscle tone. It occurs during posture maintenance. It is usually
      bilateral and, in this case, is observed in metabolic encephalopathy. Unilateral
      asterixis is more uncommon. We report 12 cases which occurred in patients with
      focal brain lesions. In all cases asterixis involved the upper limb and the lower
      limb in only 2 cases. Asterixis was transient, discrete and always associated
      with other neurological signs. The causal lesions (7 infracts, 2 haematomas, 2
      abscesses, 1 meningioma) were unique in 7 cases and multiple in 5. Asterixis was
      always contralateral to the unilateral lesions. Lesions mainly involved the
      thalamus (7 cases) and other structures (lenticular nucleus, frontal lobe,
      internal capsule, precentral regions and cerebellum). The frequency of thalamic
      involvement suggested dysfunction of the thalamo-cortical loop.

PMID- 8761620
TI  - [Automatic motion analysis of gait in patients with Parkinson disease: effects of
      levodopa and visual stimulations].
AB  - Gait analysis of 13 patients affected by Parkinson's disease (PD) and 7 healthy
      elderly volunteers was performed with a fully automatic motion analyser. The
      recording included stride parameters for walking velocity, stride length, stride
      duration and swing time. Maximal amplitudes of rotation of the hip, knee and
      ankle were also recorded. The analysis was performed for the PD's patients before
      and after L-Dopa intake. All the patients walked with and without transversal
      stripes on the floor. The contrasting white lines were 45 cm apart. After
      medication, the stride length, the velocity and the swing phase duration were
      significantly increased. The movements around the hip, knee and ankle joints that
      were initially reduced, poorly increased after L-Dopa intake. When stripes were
      placed on the floor, no significant changes occurred for the overall group of
      patients. Seven parkinsonian patients did improve with visual guidance,
      increasing their stride length and their speed. Some rotations of hip and knee
      were also influenced by stripes. This sub-group of patients was characterized by
      older age, a slower walking velocity, a smaller stride length and a shorter swing
      time. We correlated the sensitivity to visual cues to the defect of the visual
      contrast sensitivity that has been established in PD by several recent works.
      Locomotion on the transverse lines might have produced a motion perception at a
      rate determined by the speed of the patient. For appropriate intervals between
      stripes, one can hypothesise that the resulting visual stimuli belonged to a
      range of spatio-temporal frequencies that are decreased in patients with PD.

PMID- 8761621
TI  - [Spontaneous regression of primary cerebral lymphoma].
AB  - We report on a 55 year-old women with spontaneous remission of a primary cerebral
      lymphoma. Initial CT scan showed a left hemispheric lesion. With steroid therapy,
      this lesion disappeared. Nine months later, a new lesion appeared in the right
      frontal lobe. Follow-up CT scan 3 weeks later, without any treatment, showed
      complete resolution of this lesion. We conclude that primary cerebral lymphoma
      may have spontaneous remission.

PMID- 8761622
TI  - [Spontaneous spinal epidural hematoma: 2 cases].
AB  - The authors report on two cases of spontaneous spinal epidural hematomas with
      atypical subacute clinical presentation and good recovery after surgical
      treatment. Etiologies, physiopathology, early diagnosis and treatment are
      considered through a brief review of the literature.

PMID- 8761623
TI  - [Genetic susceptibility in multiple sclerosis].

PMID- 8761624
TI  - [Amyloidosis, protein conformation dynamics and neurologic diseases].
AB  - The abnormal protein which accumulates in the extracellular space in the central
      nervous system in Alzheimer's disease and prion diseases could result from
      similar mechanisms. Many studies have demonstrated that the abnormal protein is
      resistant to proteolytic agents. This resistance is correlated with a
      modification in the conformation of the protein, inverting the ratio of alpha and
      beta helix structures. This change in conformation could be the cause of the
      central nervous system lesions. The mechanism of the modification in conformation
      could be related to a process of hydrophobisation of the protein resulting from
      mutation. A hydrophilic amino acid would be replaced by a hydrophobic amino acid
      or in sporadic forms, modifications in the environment of the peptide may lead to
      physical and chemical aggressions. Hydrophobisation of the two proteins could
      later lead to formation of polymers and then insoluble aggregates with the
      physical and chemical characteristics of the amyloid substance. Polymerisation
      could be triggered by the formation of protein dimers which would be, in one
      case, an endogenous protein, PrP, and in the other exogenous proteins coming from
      the environment.

PMID- 8761625
TI  - [Neuropsychological testing of 5 patients with Parkinson's disease before and
      after neuron graft].
AB  - Five patients with idiopathic PD were followed by neuropsychological tests after
      brain fetal neuronal transplantation. The following tests were used in order to
      assess memory as well as visuospatial and frontal functions: MMSE, Mattis Scale,
      Wisconsin Card Sorting Test, Stroop task, word fluency tasks, 15-objects test,
      WAIS-R (Digit span, Arithmetic, Block design, Pictures completion, Pictures
      arrangement), learning of 15 words of Rey, WMS-R (Logical memory) and Visual
      memory of L. Israel. The same tests were performed before, then one year
      following the transplantation. Pooled data did not show any significant
      difference between pre and post-operative tests. Individual results varied among
      patients: 2 remained unchanged, 1 had a pathological deterioration which
      increased after one year, 1 had some frontal symptoms whereas the last patient
      improved. Our data confirm that this surgical procedure do not induce permanent
      neuropsychological deficits, but do not indicate at the present time any clear
      effect of dopamine reinnervation on cognitive functions.

PMID- 8761626
TI  - [Interhemispheric disconnection syndrome caused by partial infarction of the
      corpus callosum: neuropsychological study and MRI].
AB  - A partial syndrome of hemisphere disconnection was observed in a 63 year-old
      woman, following an anterior and middle corpus callosum infarct on MRI. Notably,
      we found left ideomotor apraxia, diagonistic apraxia, left-year extinction on
      dichotic listening, but no left-hand anomia nor left visual field anomia. A left
      tactile extinction in dichaptic condition is interpreted as resultant of a
      dysregulation of the attentional balance between the two hemispheres. This
      detailed neuropsychological study permits a correlation between the callosal
      syndrome and the lesion. We suggest that an occlusion of the anterior callosal
      artery could explain this limited ischemia.

PMID- 8761627
TI  - [Interhemispheric disconnection, Balint's syndrome and persistent anarthria:
      Marchifava-Bignami disease with white matter hemorrhage].
AB  - A 37-year-old alcoholic right-handed man developed a complex neuropsychological
      picture following a mild head injury and a severe confusional state. Prominent
      features were Balint's syndrome, signs of interhemispheric deconnection, and
      speech disorders with anarthria and dysprosody. Iterative CT scans showed
      pathognomonic hypodensities of the genu and splenium of corpus callosum,
      confirmative of Machiafava-Bignami disease. After a two years follow-up, a
      favourable outcome was observed despite haemmoragic transformation of bilateral
      necrotic lesions of the parietal white matter, an exceptional neuropathological
      fact. This case is demonstrative of the possibility of articulate speech
      impairment when lesions of both corpus callosum and subcortical white matter are
      present. It also raises several aetiopathogenic problems which are discussed.

PMID- 8761628
TI  - [Akinetic mutism with right hemiplegia caused by infarction in the territory of
      the left anterior cerebral artery].
AB  - A 65 years old woman with chronic high blood pressure and diabetes mellitus
      presented with a mutism akinetic of sudden onset and a right total hemiplegia
      with a Babinski sign secondary to a left anterior cerebral artery infarction. She
      had had six months earlier a transient gait disturbance. At that time, the CT
      scan showed lacunar infarcts of the head of both caudate nuclei.
      Neuropathological examination revealed that the left infarction of the anterior
      cerebral artery involved the superior frontal gyrus, the supplementary motor
      area, the cingulate gyrus and the corpus callosum. There were also multiple
      lacunes of the head of both caudate nuclei, anterior limb of the internal
      capsules, white matter, basal ganglia and thalami. The mutism akinetic was
      thought to be the result of a bilateral disruption of a functional loop including
      on each side, the supplementary motor area, the cingulate gyrus, the subcallosal
      tract and the head of the caudate nucleus. On the right side, the lesion of the
      caudate nucleus could have interrupted this loop normally involved in the
      induction of voluntary movements and in the communication with the external
      surroundings.

PMID- 8761629
TI  - [The man with 6 arms. An analysis of supernumerary phantom limbs after right
      hemisphere stroke].
AB  - Consequently an infarct in the territory of the right middle cerebral artery, a
      77-year old man had a complete left sensory motor hemiplegia, with left neglect.
      For several weeks, he described the existence of one and more supernumerary
      phantom limbs. The patient's adamant and delusional conviction of their reality
      caused him considerable distress. Without being anosognosic he was not completely
      aware of his disorder, and had slight difficulties in judging what was plausible.
      The mechanisms underlying this delusion concerning specific parts of the body
      probably involve multifactorial disorders: first, a sensory deafferentation
      source of a distorsion of the perceived body schema; second, a resulting
      discrepancy between the perception of the body schema and its innate
      representation; third abnormalities of self-awareness and of self-judgement,
      leading the patient to argue forcellully in favor of incongruous
      rationalizations.

PMID- 8761630
TI  - [MRI aspect and course of supra-tentorial sarcoidosic lesions].
AB  - Central nervous system lesions resulting from sarcoidosis occur in 5% of cases,
      but supratentorial mass lesions are uncommon. We report 3 cases of intracranial
      pseudo-tumoral lesions, due to sarcoidosis: 1 woman and 2 men. Clinical features
      included left facial myoclonus, headache and vertigo, right hemiparesis and
      unique general seizure. Sarcoidosis was diagnosed upon conjonctival biopsy in the
      first case, infiltrative lesions of the lungs and mediastinal lymph nodes in the
      second case, and intracerebral lesion plus lymph nodes biopsies in the last case.
      In the first case, CT scan and MRI images showed diffuse subcortical high signal,
      suggesting pachymeningitis with vasogenic oedema. In the second case, GT scan and
      MRI revealed numerous small granuloma in the left rolandic area, and one in the
      striatum. In the third case, CT scan showed an enlargement of the left temporal
      horn, due to an enhanced left periventricular lesion. MRI with gadolinium showed
      that the lesion encircled the ventricle horn. In all cases, clinical and
      radiological improvement was obtained after corticoid therapy.

PMID- 8761631
TI  - [Cerebellar syndrome associated with Hashimoto's encephalopathy].
AB  - A 38-year-old man presented with an acute confusional state associated with
      cerebellar signs in left upper limb. Hashimoto's thyroiditis was discovered.
      Brain magnetic resonance imaging with T2-weighted sequences revealed a high
      intensity signal in the left cerebellar hemisphere. The patient received
      corticosteroids and thyroid hormonal therapy, which was followed by a rapid
      clinical improvement. The association of an acute confusional state and of
      cerebellar signs should suggest a Hashimoto's encephalopathy.

PMID- 8761632
TI  - [Meningomyelitis disclosing Behcet's disease].
AB  - The authors report a patient who developed a meningo-myelitis attributed to
      Behcet disease. Spinal MRI assessed spinal involvement. Among neurological
      manifestations of Behcet disease, isolated spinal cord involvement is infrequent.
      Dramatic improvement of neurological symptoms was obtained after steroid and
      immunosuppressive treatment.

PMID- 8761633
TI  - [Subacute distal motor neuropathy disclosing malignant non-Hodgkin lymphoma:
      improvement under chemotherapy].
AB  - A non Hodgkin's lymphoma strictly located in the bone marrow, was discovered in a
      patient presenting with asymetric muscle weakness of upper and lower limbs. Both
      the lymphoma and the neurological syndrome were successfully treated with
      chemotherapy.

PMID- 8761634
TI  - [New hypotheses in asthma: the mastocytes].
AB  - Increasing progress has been made in the understanding of the biology of mast
      cells. The precursors of mast cells leave the bone marrow in a non-differentiated
      form as CD34+ cells. The presence of mast cells growth and differentiation
      factors controls in tissues maturation of different mast cells phenotypes. The
      main factors are the mast cell growth factor SCF (stem cell factor), NGF (Nerve
      Growth Factor), and IL-3 (Interleukin-3). The potential role of each of these
      factors in the airways is discussed. An altered production of these growth
      factors in the airways of asthmatic patients might be the cause of the presence
      of an increased number of mast cells and of phenotypic modifications in the
      bronchi of these patients.

PMID- 8761635
TI  - [Morbidity and mortality induced by asthma in 1996].
AB  - Because asthma is an episodic disease with intermittent and unpredictable
      manifestations, the patient must be constantly on the alert to his condition,
      causing permanent stress for the entire family. The time and effort spent for
      treatment can be a great burden for the patient and his family and friends,
      sometimes causing a handicap in school or profession life. Consequently, the way
      relatives, friends, and society in general perceive asthma can have an effect on
      their reaction to the disease. Dominant attitudes in a given social setting
      create a standard, socially accepted definition of the disease which can play an
      essential role in asthma-induced morbidity. The link between morbidity,
      mortality, poverty and quality of health care is a constant feature in
      epidemiological data on asthma. In areas where pollution is low or access to
      health care unimpaired, survival curves for asthma patients are similar to those
      for the non-asthmatic population, demonstrating the role of the social context in
      asthma-induced mortality. One must however be very prudent in analyzing
      epidemiological data on asthma since most published work has been conducted in a
      specific cultural and medical context, often with a health care structure which
      is quite different from the situation in France. In order to improve the
      situation of the asthma population in France, two essential questions, "which
      patients suffer from their asthma?" and "which patients die from their asthma?"
      must be answered. Then in order to reach those patients which do not consult, the
      general population should then be informed. Important targets include better
      informing general practitioners, facilitating access to health care, training
      asthma patients, and improving social aid to compensate for the patient's
      economic incapacity. No matter what improvements in treatment are acquired, in
      these factors are not taken into consideration, there can be little hope of
      improving asthma-induced morbidity and mortality.

PMID- 8761636
TI  - [Role of atmospheric pollutants in asthma].
AB  - Air pollution can be divided into two basic types, industrial acid pollution
      (black smoke-dust particles sulfur oxide) and photochemical pollution (nitrogen
      oxides-ozone from automobile exhausts). In western countries, industrial
      pollution has greatly decreased while photochemical pollution has remained stable
      or increased depending on the area. In animal models, all types of air pollution,
      at high concentration, have an effect on the airways: irritation, facilitation of
      allergic sensitization, reduced resistance to infections. In humans, is the
      prevalence of asthma higher in polluted areas? Most surveys have found that the
      prevalence of respiratory, ear-nose-throat, and bronchial symptoms is higher but
      not symptoms of asthma. The surveys comparing East and West Germany suggest that
      irritation (repeated rhinobronchitis) is related to acid-particle pollution. The
      higher prevalence of allergic diseases in ex-West Germany does not appear to be
      related to photochemical pollution but rather to western lifestyle in general. In
      addition, changes in air pollution have an effect on the clinical and functional
      score in asthma patients, affecting the demand for medication and health care. Of
      particular importance for health care is the fact that these effects occur at
      concentrations below "standard" levels of pollution.

PMID- 8761637
TI  - [New aero-allergens].
AB  - As the number of proteins recognized as causing allergic respiratory diseases
      increases, new aero allergens have appeared in the animal and vegetable realms,
      both in home and professional environments. Lepidoglyphus destructor and Blomia
      tropicalis, two mites found in storage areas, are particularly important in
      agricultural areas and in homes. Over the last ten years, the frequency of
      reactions to cockroaches has also increased in several countries. The
      allergenicity of non-biting insects is a frequent cause of allergy in certain
      countries including Japan. Chironomides cause respiratory diseases in
      professional and outdoor environments. The important role of Alternaria, a mold,
      in producing severe asthma has also been demonstrated. The pathophysiology of
      pollen-induced asthma has been shown to result from pollen allergens carried by
      particles less than 5 microns in diameter. Cyprus and ash tree pollen also cause
      an increasing number of pollinoses and flowers can cause rhinitis and asthma.
      Respiratory allergy to Ficus benjamina inaugurated a new type of allergies caused
      airborne allergens from non-pollinating plants. Allergy to latex raises a
      particular problem for health care workers. The immunochemical structures of the
      major and minor airborne allergens are now better known and the homologous
      structures of different allergens largely explains certain cross-reactions. In
      the future, recombinant allergens will probably be used to better understand the
      role of allergens in inducing and maintaining the allergic reaction and should
      help in our approach to diagnosis and therapy.

PMID- 8761638
TI  - [Value of imaging in asthma].
AB  - While the definition of asthma is based on clinical manifestations and
      respiratory function, imaging is widely used in acute asthma. We attempted to
      exploit the resources of high-resolution computed tomography to better study the
      fine structure of the airways. In acute asthma and at the first consultation for
      asthma, standard radiograms provide little precise information on the bronchi
      excepting cases with major lesions. High-resolution computed tomography can
      identify persistent bronchial and lung lesions which significantly correlate with
      clinical expression. These lesions are more frequent in non-allergic persons. We
      were able to obtain dynamic images demonstrating the anatomic variations in
      bronchial obstruction occurring after a provocation test. These applications are
      now in the clinical research stage. High-resolution computed tomography may soon
      play a role in clinical management of patients with asthma.

PMID- 8761639
TI  - [Is the bronchial provocation test justified in occupational respiratory
      disease?].
AB  - Specific bronchial provocation tests can confirm the diagnosis of occupational
      respiratory disease and also identify the causal agent of occupational asthma.
      The changes in French regulations established in 1993 which allow other agents to
      be recognized as causal in compensation for occupational diseases has increased
      interest in these tests. The different diagnostic methods used for occupational
      asthma are discussed here with special emphasis on limitations in each case:
      history taking, immunological investigations, respiratory function tests,
      measurement of peak flow during occupational activity and holidays, sequential
      measurements of non-specific bronchial hyperreactivity. The difficulty in
      standardizing specific provocation tests used for occupational asthma is related
      to the wide variety of causal agents which can be inhaled as gas, aerosols or
      powders. Because of the required precautions, these tests must be performed by
      specialized personnel in hospital units. There are also limitations to specific
      provocation tests. False positives require placebo tests and false negatives may
      result from insufficient identification of the causal agent. Exposure time may be
      too short or concentrations too low, and may depend on how long the causal agent
      has been evicted. Specific provocation tests may be avoided when the clinical
      history reveals a typical situation due to an agent known to cause occupational
      asthma and repeated peak flow measurements at the working site and/or
      immunological sensitisation tests provide objective evidence. But in a certain
      number of cases, specific investigations are required to obtain the precise
      etiological diagnosis required to evict the allergen rapidly and avoid chronic
      asthma.

PMID- 8761640
TI  - [Occupational asthma: medical and social prognosis].
AB  - The medical and social prognosis of occupational asthma has only been assessed
      with retrospective studies. The main findings are analyzed here. The wide range
      of methods used to obtain a positive diagnosis of occupational asthma and more or
      less complete eviction of the causal agent hinder interpretation of the results.
      Nevertheless, the findings reported in 15 studies focusing on the medical
      prognosis have shown that in 70% of the cases, occupational asthma remains
      symptomatic after eviction. The number of years the asthma existed at diagnosis
      is higher in subjects who remain symptomatic after eviction. In most patients
      with occupational asthma, the absence of eviction leads to accentuation of the
      obstructive syndrome and non-specific bronchial hyperreactivity. When the
      occupational disease has been recognized, the social-professional consequences
      unfortunately often include loss of employment and lower revenue.

PMID- 8761641
TI  - [Asthma in children].
AB  - Asthma is the most frequent chronic disease in children. Its prevalence has
      increased over the last 20 years. In the newborn, the diagnosis can be retained
      after 3 episodes of whistling dyspnea. Asthma often appears following respiratory
      syncytial virus bronchiolitis. In the child, asthma frequently accompanies
      allergy to airborne allergies. Adolescence, often a difficult period, carries the
      highest risk of severe episodes. A minimal asthma workup should be performed in
      all children with asthma including a search for an allergen and respiratory
      function tests. Asthma in childhood can be classed in different categories
      depending upon the nature of the allergen and the degree of bronchial
      obstruction. Recommended management has been the object of several consensus
      conferences and should include symptomatic treatment and prevention, adapted to
      the age of the child and the severity of the episodes. To be effective,
      preventive treatment must be given daily and for a long period.

PMID- 8761642
TI  - [Modes of administration of beta agonists in asthma].
AB  - Short-acting beta 2 agonists have a rapid and potent bronchodilating effect and
      represent the basis of treatment of acute asthma. Whatever the level of severity,
      the inhaled route is preferred because of its high efficacy/tolerance ratio. The
      doses and modes of administration depend on the severity of the airway
      obstruction, the site of management and the available devices. Long-acting beta 2
      agonists are administered as regular treatment in moderately-severe to severe
      chaonic asthma in association to inhaled corticosteroids, mainly by the inhaled
      route whereas the oral route may be considered for the administration of
      prodrugs.

PMID- 8761643
TI  - [Treatment of severe acute asthma].
AB  - Severe acute asthma remains associated with significant mortality. Medical
      treatment of acute severe episodes includes oxygentherapy, inhaled or intravenous
      beta-2-agonists, and high doses of systemic corticosteroids. The benefit of
      additional treatment with other agents such as nebulized ipratropium bromide,
      epinephrine and intravenous aminophylline is still not well defined. Mechanical
      ventilation, which remains necessary in case of life-threatening acute
      respiratory failure, addresses specific problems: PaCO2 may be allowed to remain
      elevated and ventilator settings should be chosen that avoid barotrauma under
      appropriate sedation. The use of inhalation anesthesics, helium or even
      extracorporeal life support necessitates further study to determine the optimal
      therapeutic strategy in those particular situations.

PMID- 8761644
TI  - [Primum non nocere: inhaled corticoids].
AB  - Several studies have been devoted to the possible deleterious effects of inhaled
      corticosteroids. These products are effective and have been widely used for
      longer and longer periods. Tests used to detect systemic effects are now quite
      sensitive allowing us to identify infraclinical purely biological effects
      resulting from minimal doses. The real value of these tests in predicting long
      term deleterious effects such as adrenal failure, osteoporosis or growth
      retardation are now recognized. However, it is difficult to incriminate
      corticosteroids alone in certain cases because "parasite" conditions are often
      created by systemic corticosteroid therapy and because asthma alone can lead to
      deleterious extrapulmonary effects which should not be considered to result from
      treatment alone, emphasizing the need for carefully controlled studies. Despite
      the description of multiple systemic effects, the clinical consequences of long
      term inhaled corticosteroids are not at all in the same range as oral
      corticosteroids. Nevertheless, there is some debate as to the strict indications
      for inhaled corticosteroids in adults and in children. The use of minimal
      effective doses in asthma is a primum non nocere.

PMID- 8761645
TI  - [Inhaled corticotherapy in asthma: when should it be started and how to stop?].
AB  - Bronchial inflammation is an almost constantly encountered feature in asthma,
      even in early stages. Corticosteroid therapy has been shown to be effective both
      in reducing bronchial inflammation and improving signs of bronchial
      hyperreactivity. The possible side effects of prolonged inhaled corticosteroids
      cannot be ignored. Thus, while the indication for inhaled corticosteroids is
      severe asthma is clear, many questions are raised in case of intermittent minor
      asthma. There is still much debate over the correct initial dose (high or low)
      and the clinical and functional criteria for dose reduction or withdrawal. We
      discuss here the modalities for starting and stopping inhaled corticosteroids in
      patients with asthma.

PMID- 8761646
TI  - [Corticoid resistance in asthma].
AB  - Incorrect application of corticosteroid treatment, whether due to non-compliance,
      misinterpretation of etiological factors, or inadapted treatment, can lead to the
      difficult problem of corticoresistance. The expression of the phenomenon are
      varied and may concern all or part of the effector cells responsible for the
      inflammatory reaction. The underlying mechanism is still poorly understood but
      appears to involve a generally acquired, though sometimes inborn or genetically
      induced, desensitization of the receptor cells. Several substitute treatments
      have been proposed including methotrexate, gold salts, cyclosporin A, but the
      results have not been very promising.

PMID- 8761647
TI  - [Reoperations after surgical treatment of lumbar stenosis].
AB  - PURPOSE THE STUDY: The aim of this study was to determine the causes of failure
      following surgical treatment of lumbar spinal stenosis, indications for redo
      surgery and factors influencing the final result. MATERIAL AND METHODS: Between
      1975 and 1992, 38 patients were reoperated after a surgical treatment of lumbar
      spinal stenosis. The mean follow-up was 34 months. All of these patients had had
      at least one previous lumbar spinal operation. Second operation was performed 35
      months on average following the previous surgery. CLINICAL EVALUATION: The
      grading scale used in this review assessed walking ability, radicular pain at
      rest and at exersion, back pain, motor deficit and sphincter dysfunction.
      Patients were evaluated before and after the 2 surgeries and at last follow-up.
      Radiological study was done from CT-scan, MRI, myelograms, static and dynamic
      standard X-rays before the first surgery and following the revision surgery.
      RESULTS AND DISCUSSION: According to our grading scale the final result was very
      good for 36 per cent of the patients, good for 24 per cent, fair for 24 per cent
      and poor for 16 per cent. The main causes of failure were post-operative
      destabilization and incomplete neurological decompression. In 56 per cent of our
      cases initial nerve roots decompression was incomplete: disc excision without
      bone resection in case of lumbar stenosis associated with disc herniation,
      incomplete lateral release, decompression of the symptomatic nerve roots only and
      not of all of them that were compressed. In these cases revision surgery was
      comprised by a new decompression. In 25 per cent of our cases post-operative
      destabilization was the cause of failure. During the previous surgery bone
      resection had been extensive: total bilateral facetectomy without fusion, wide
      laminectomy extended into the pars inter-articularis, resulting in isthmic
      fracture. Revision surgery was a posterolateral fusion with or without
      instrumentation generally associated with a new decompression. Two patients were
      reoperated on without evidence of inadequate decompression or destabilization.
      Result was poor in both. Final results were statistically better when the cause
      of revision surgery was a post-operative destabilization and when redo surgery
      was performed on surgically untouched levels. CONCLUSION: Final results were
      disappointed since only 60 per cent were good or very good results. Revision
      surgery should be avoided, by using pre-operative planning of the neural
      decompression, and by adding a fusion if a wide bone resection is necessary.

PMID- 8761648
TI  - [Spinal metastases of thyroid origin. Apropos of a series of 37 cases].
AB  - PURPOSE OF THE STUDY: Define a specific therapeutic for spinal metastasis from
      thyroidal origin. MATERIAL: A retrospective series of 37 patients treated between
      January 1978 and January 1993 was made. The sex ratio was 29 women for 8 men with
      an average age of 59.5. The prevalent histology has a vesicular type (19 cases
      which represents 51 per cent). The metastasis are mostly found at the dorsal
      level (48.6). METHODS: The different parameters analysed for this study of 37
      patients were: invaded segment of the vertebra (anterior, middle, posterior or
      total), Tokuhashi score, epiduritis extent, patient age, histological type and
      iodiosensibility. RESULTS: Out of 37 patients, 3 were lost for follow-up, 7
      metastasis were treated carcinologically ("en bloc" resection). 30 were treated
      palliatively depending on the clinical symptoms: neurological, mechanical, or
      pain. The osseous metastasis exists in 56 per cent of the cases at the time the
      primitive neoplasy was discovered, and their presence burdens the final
      prognostic. 21 patients died with an average survival of 21 months, 13 patients
      survived with a mean follow-up of 50 months, 50 per cent of the patients had a
      vertebra totally involved with only 13 patients with neurological signs (4
      Frankel A, 3 Frankel B, 4 Frankel C and 2 Frankel D). DISCUSSION: The analysis of
      the results shows that the pejorative criteria in case of vertebral metastasis of
      thyroidal cancer are the score of Tokuhashi inferior to 7, the whole affected
      vertebra, the epiduritis on 3 levels, the age of the patient superior to 65 and
      the idiosensibility of the metastase. The surgery do called carcinological gives
      very good results with 5 surviving patients out of 7. CONCLUSION: When reading
      this study it seems that, in front of vertebral metastasis from thyroidal origin,
      we should choose the most radical therapeutic attitude as much as possible. This
      strategy finds its justification by the fact that the thyroidal cancer spreads
      out slowly giving a survivorship superior to 12 months in case of metastatic
      vertebral affection. The importance of the tumoral reduction is connected with
      the efficiency of the iodiotherapy (for differentiated histological types). This
      is a considerable adjuvant treatment for this kind of cancer.

PMID- 8761649
TI  - [Recurrent anterior and multidirectional instability of the shoulder].
AB  - PURPOSE OF THE STUDY: Surgical treatment for recurrent anterior instability
      associated to multidirectional shoulder hyperlaxity: results analysis. MATERIAL:
      Twenty five patients operated for recurrent anterior dislocation or subluxation
      with multidirectional hyperlaxity. Age at operation was low (22 years old), there
      were more females than males, instability was bilateral in 52 per cent cases.
      METHOD: Five patients underwent a capsular shift followed by a four weeks post
      operative immobilization. Twenty patients underwent a bone block procedure with
      the coracoid process associated with a modified capsular shift. Inferior half of
      the subscapularis muscle was left intact under the coraco-biceps tendon. RESULTS:
      The results were fair with only 52 per cent excellent or good results. Ten
      patients (40 per cent) presented a recurrence either a dislocation or a
      subluxation. Hyperlaxity recurred in all but three patients. The procedure didn't
      influence the results which were related to the antecedent: the patients with a
      previous history of voluntary recurrent posterior subluxations achieved 33 per
      cent fair or poor results. Patients with previous history of recurrent anterior
      subluxation achieved 100 per cent poor results, whereas the patients without
      antecedent achieved 85 per cent good to excellent results. DISCUSSION:
      Establishing a difference between laxity and instability helps to analyse the
      patients with an unstable shoulder rather than considering traumatic or
      atraumatic onset of the instability. Identification of the hyperlaxity and of the
      antecedents must influence the therapeutic discussion. CONCLUSION: We recommend
      to use the term multidirectional hyperlaxity rather than multidirectional
      instability to characterize these patients.

PMID- 8761650
TI  - [Stabilization of the hindfoot by talonavicular arthrodesis. Results apropos of
      50 cases].
AB  - Hindfoot stabilization can be obtained by an isolated talonavicular arthrodesis
      as well as a triple arthrodesis. MATERIAL: There were 27 cases of unstable
      neurological foot, 13 cases of Rhumatoid foot, 7 cases of flat feet and 3 cases
      of post-trauma arthritis of the talonavicular joint. The procedure was, in all
      cases, a talonavicular arthrodesis, associated in some cases to a lengthening of
      the Achilles tendon, tendon transfer and forefoot correction. METHOD: 50 cases
      were reviewed with a mean follow-up of 40 months. RESULTS: There were 18 per cent
      cases of non-union. This could be explained by 2 technical errors: bad
      cartilagenous resection of the surfaces and unstable bone fixation. No subtalar
      mobility was noted in all cases. Only one case had a midtarsal mobility
      associated to a non-union. 39 feet had a normal heel axation. In most cases
      functional improvement was significant with a painless gait. DISCUSSION: Hindfoot
      stabilization can be obtained by an isolated talonavicular arthrodesis. Non-union
      could be avoided by a better surgical technique and a cast immobilization of 2
      and a half months. The pre-operative deformities should be reduced manually,
      because isolated fixed valgus and varus can not be corrected by an isolated
      talonavicular arthrodesis. In conclusion, the indications are: An early valgus
      deformity of the hindfoot in rhumatoid arthritis. The aim is to avoid a fixed
      valgus deformity. Neurological induced equino varus deformities specially after
      stroke and other reducible neurological deformities. Flat foot due to posterior
      tibialis insufficiency. Isolated arthritis of the talonavicular joint.

PMID- 8761651
TI  - [Tenotomy of the psoas muscle in slow reduction of congenital hip dislocations].
AB  - PURPOSE OF THE STUDY: The aim of this study was to relate the efficacy of cutting
      the psoas tendon in case of high congenital hip dislocation treated by slow
      reduction according to Somerville-Petit. MATERIAL: Twenty psoas tenotomies were
      realised between 1982 and 1992. The average age was 11 months 15 days old, they
      were 15 girls and 5 boys. Among them, only 9 patients had never been treated.
      METHOD: By a short surgical approach close to the lateral lip of Scarpa's
      triangle, we cut the psoas tendon at the musculotendinous junction doing this
      suppresses the obstacle that interferes with the femoral head coming down.
      RESULTS: Results have been evaluated on clinically and especially radiologically.
      All hips remain stable except one case. A graduated subluxation of the hip
      occured after removal of the plaster. 18 hips have been revised between the third
      and fifth year. Clinical results were excellent, on radiological controls 5 hips
      were considered flawless, 11 satisfying, and 2 were imperfect. Only 2 children
      have been seen ten years later with excellent clinical and radiological results.
      DISCUSSION: The hypertrophic psoas tendon interposes between the femoral head and
      the acetabulum creasing the capsule and the limbus. Cutting tendon of the psoas
      will decrease the numerous unexplained failures that occured during slow
      reduction according to Sommerville-Petit method. The use of these surgical
      techniques may make more outstanding the tenotomies time. CONCLUSION: Tenotomy of
      the psoas tendon realized by a short surgical approach without any articular
      effraction, allowed us to obtain complete reduction of the hips dislocation in
      these 20 patients.

PMID- 8761652
TI  - [Distal intra-articular resection of the calcaneus in the treatment of severe or
      recurrent congenital clubfoot].
AB  - INTRODUCTION: Secondary adaptive bone changes and joint distorsions in clubfoot
      may present a barrier to adequate correction of the deformity. The purpose of our
      study is to show how the lateral excision of the calcaneus distal part as
      described by Lichtblau, in combination with an appropriate medial release allows
      better correction of forefoot deformity, with less recurrence rate. MATERIAL AND
      METHODS: Between 1974 and 1982, 43 feet in 38 patients underwent this type of
      surgery. Lateral excision o the calcaneus was decided preoperatively in 34 feet,
      for recurrence of the forefoot deformity following previous surgery. In the
      remaining 9 feet, this lateral excision was decided intraoperatively, because of
      an uncomplete correction of the fore part of the foot, despite an adequate
      posteromedial release. The resected angle from the distal intra-articular part of
      the calcaneus varied from 10 to 30 degrees with an average of 15 degrees.
      RESULTS: All our results were evaluated at end of growth. Mean age at follow-up
      was 15 years and 4 months, with an average period of 10 years and 7 months
      following surgery. The average forefoot adduction moved from 21 degrees
      preoperatively to 1 degree at last follow-up. The clinical calcaneocuboid
      mobility was preserved in 37 cases. Four types of complications were encountered
      in 7 patients: pain in 5 cases, calcaneocuboid fusion in 6 cases, recurrence of
      deformity in 2 cases, and overcorrection in 5 cases; this last complication was
      related to intraoperative overcorrection rather than a progressive deterioration
      of the result, and had no clinical significance. No overcorrection was seen after
      calcaneocuboid fusion. We have found no relation between age at surgery, and the
      incidence of calcaneocuboid fusion, but the two cases operated on children under
      one year old, ended up with a bad result. DISCUSSION: The resection of a single
      side of a joint may permit normal joint function to be retained. The resected
      cartilage is replaced by a fibrocartilage that resembles the original articular
      cartilage, provided the resected defect is deep enough to allow vascularization
      from the underlying bone. CONCLUSION: The success of this method depends on an
      accurate surgical technique, as described by its promoter. It can be of great
      help in severe and complicated clubfeet. It achieves the goal with a
      calcaneocuboid function often preserved.

PMID- 8761653
TI  - [Outcome of hip shelf arthroplasty in adults after a minimum of 15 years of
      follow-up. Long term results and analysis of failures of 56 dysplastic hips].
AB  - PURPOSE OF THE STUDY: The goal of this study was to evaluate late results of hip
      shelf arthroplasty in adults after a minimum of 15 years follow-up. MATERIAL: 65
      hip shelf arthroplasty performed for painful hip dysplasia between 1964 and 1977
      were studied retrospectively in 1992. These 65 procedures were performed in 57
      patients mean aged 32 +/- 14 years [17-56]. Nine patients (9 hips) were excluded
      (2 deceaded, 5 lost for follow-up, and two reoperated because of severe
      infection). Consequently, the functional results were evaluated for 56 hips (48
      patients). Before surgery, according to Merle d'Aubigne's hip rating system, all
      the hips were painfull (mean pain score was 2.6 +/- 1.7 [0-5]). On radiography,
      all the hips had a dysplastic acetabulum and arthritic changes. Arthritic changes
      were severe in 32 hips (57.1 per cent). METHODS: The hip shelf arthroplasty was
      carried out according to Roy-Camille. 10 hips had additional varus femoral
      osteotomy. The 48 patients (56 hips) included were evaluated by means of Merle
      d'Aubigne's hip rating system and AP and false lateral weight-bearing Xrays. In
      1992, 24 procedures were changed for total hip replacement (THR) (17 before 15
      years (early failure) and 7 after 15 years of follow-up (late failure)). These 24
      hips were included with their last hip rating observed just before THR. Survival
      analysis was performed according to Kaplan-Meier using date of revision for THR
      as end-point. RESULTS: After 16.1 +/- 5.6 years of follow-up the functional score
      for 56 hips was: excellent in 4 hips, very good in 7 hips, good in 10,
      satisfactory in 14, poor in 17, and bad in 4. The survival rate established for
      65 hips was 60 per cent at 15 years and 40 per cent at 21 years. Only 39 hips
      shelf arthroplasties were still functional after 15 years (mean follow-up 19.1 +/
      3 years [16-28], but 18 hips (46.1 per cent) were painfree or slightly painful
      (pain score to 5 or 6). Among these 39 hips, the results were excellent in 4
      hips, very good in 7 hips, good in 10, satisfactory in 10, poor in 6, and bad in
      2. Arthritic change was the main reason for failures: the Kaplan-Meier survival
      rate at 21 years was 87 per cent when arthrosis was slight and only 15 per cent
      and 42 per cent when arthrosis was moderate to severe (p = 0.0001). The adverse
      effect of arthrosis was promoted by lack of congruency for early failures, and by
      severity of dysplasia and hip subluxation for late failures. The additional
      femoral varus osteotomies had no influence on functional or radiographic outcome.
      DISCUSSION: Our study indicated that hip shelf arthroplasty performed for painful
      acetabular dysplasia in adult has a 40 per cent probability survival rate at 21
      years. The high rate of revision (42.8 per cent) could be related to the
      prevalence of severe pre-operative arthrosis. The low rate of lost for follow-up
      (8.7 per cent) and the long follow-up period (16.1 years) made our conclusion
      reliable. CONCLUSION: In spite of a high revision rate we recommend shelf
      athroplasty to treat acetabular dysplasia in adults. This procedure, very
      reliable in cases of moderate arthrosis, could be performed in cases of severe
      arthrosis to delay and make easier THR, but a low survival rate could be expected
      unless dysplasia, lack of congruency and subluxation were mild.

PMID- 8761654
TI  - [Lisfranc's fracture-dislocations].
AB  - PURPOSE OF THE STUDY: Classicaly Lisfranc fractures dislocations are unusual. Our
      study is based on 69 observations from January 1974 to January 1992. MATERIAL AND
      METHODS: Fractures occured during tremendous impacts with a sex ratio of two men
      for one woman. The authors insist on the diagnostic value of good quality
      standard x-rays. Using Trillat's classification, we had 19 homolateral spatular
      fractures dislocations, 22 homolateral columno-spatular, 8 divergent columnar and
      19 divergent columno spatular. A dislocation was reduced in emergency before
      radiography. The treatment consisted in orthopedic reduction and plaster 7 times,
      percutaneous kwire 2 times, immediate arthrodesis 5 times, open reduction and
      internal fixation with kwires 55 times. Post-operatively, 8 complications were
      noticed. 11 secondary arthrodesis were made with reference to failures of
      previous methods. They have been performed from 9 months to 5 years after the
      initial traumatism due to a painful ankylosis in bad position or arthrosis. The
      arthrodesis was total 6 times, partial lateral 2 times, partial medial 3 times.
      RESULTS: 63 patients were reviewed with a minimum follow-up evaluation of two
      years and a maximum of 9 years. The results show that we must reduce the
      tarsometatarsal fracture dislocations even if the displacement is minimal and we
      must fix them. The most satisfactory means seem to be open reduction if the least
      anatomical defect exists. Immediate, total arthrodesis reposition is suitable
      when an important articular comminution exists. If the total secondary
      arthrodesis reposition gives good results, its realization is sometimes
      difficult. The lateral partial arthrodesis must be discontinued, because they
      don't seem logical. The medial partial arthrodesis didn't prove its superiority,
      compared with total arthrodesis. DISCUSSION: The reduction of Lisfranc's
      dislocation is essential. The single case not unreduced has given a bad result as
      shown in the litterature. When the orthopedic treatment is well-made, the result
      is good. The open reduction followed by an axial fixation has only given 56 per
      cent of good results. The main reason of these bad results is an important
      comminution which should have practised an immediate arthrodesis reposition and a
      bad reduction. We must be aware on the quality of the anatomical reduction. The
      secondary arthrosis appeared principally in cases where the reduction was
      defective (13 observations out of 50). The 5 immediate arthrodesis have all given
      a good result. CONCLUSION: The retrospective study of the series teaches us to
      reduce the tarsometatarsal fractures dislocations even if the displacement is
      minimal and to fix them. We must make a wider place to the immediate arthrodesis
      reposition.

PMID- 8761655
TI  - [Transverse fracture of the body of C2. Apropos of a case].
AB  - INTRODUCTION: A new fracture of the body of C2 is described. The mechanism is an
      axial compression producing a body sagittal fracture spreading to the posterior
      arch with a separation effect. CASE REPORT: A 29 years old female fell from the
      second floor. Examination showed a head injury and upper neck stiffness. Specific
      radiological signs was reported on the standard X-ray. The fracture involved the
      body and the lamina of C2 with a sagittal separation. No neurological abnormality
      was detected. CT scan provided additional information and allowed the survey of
      bone healing. Non operative treatment was undertaken by minerva jacket for four
      months carying complete recovery. DISCUSSION: The mechanism of this fracture
      seems to be similar to Jefferson's fracture. Review of the literature showed that
      fractures of the body of C2 are uncommon. Their different types are discussed.

PMID- 8761656
TI  - [Inter-trochleo-bicondylar fracture of the femur. An unusually traumatic lesion.
      Mechanism. Therapeutic implications].
AB  - The authors present a curious type of fracture of the distal end of the femur.
      They discuss the mechanism and the factors responsible for that lesion. The
      treatment and results are finally presented. MATERIAL: A 65 years old female,
      submitted to a crash accident while driving a car, with a seat in maximaly low
      position. She presented a bilateral open transverse fracture of the patella
      associated in the right limb to a fracture line between condyles and the patellar
      surface of the femur. METHOD: Bilateral osteosynthesis of both patella had been
      realised in emergency through a transverse approach. Through the fractured right
      patella two anteroposterior screws had been used to fix the fractured femur.
      RESULT: A plaster cst had been used for three weeks. Full weight bearing was
      permitted after three months. Full range of motion of both knees was noticed
      after six months follow-up. DISCUSSION: The femoral fracture could have been
      fixed by another device like D.C.S. platescreen but it would be weaker. That type
      of fracture was produced because of flexed low position of the knee at the moment
      of the accident. Usually, supra-condylar femoral fractures are due to a force
      vector applied on the upper extremity of the tibia without any patellar fracture.
      In our case, the patella involved associated to a fracture line between the
      condyles and the patellar surface. The structural anatomy (noeud sutural de
      Chevrier) explains the solidarity of the two femoral condyles.

PMID- 8761657
TI  - [Scaphoid fracture associated with displaced fracture of the distal end of the
      radius in children. Apropos of a case].
AB  - A child of 13 years, victim of a fall on his wrist at dorsal flexion position; he
      presented a scaphoid fracture associated with a displaced fracture of the distal
      end of the radius. The radius fracture was reduced under general anesthesia, by
      external manoeuvre; the consolidation was obtained after 10 weeks of plaster cast
      immobilization. The follow-up was of two years, with a good clinical and
      radiological result in spite of a non union of the Ulnar-styloid. It is important
      to remember this exceptionnel association in children not to forget the scaphoid
      fracture.

PMID- 8761658
TI  - [Multiple bone lesions of a type of disseminated African histoplasmosis in a
      Togolese immunocompetent child].
AB  - The authors report one case of disseminated African's histoplasmosis with
      numerous bones in Togolese immunocompetent child. The left tibia and fibula, the
      collarbones and the acromion were the bones mostly affected. The chronic
      fistulate lesion of the left leg associated with skin lesion allowed to evoke the
      diagnosis, this being confirmed by histological examination. The authors review
      the different diagnosis which will be discussed considering the radiographic
      appearance of african's histoplasmosis.

PMID- 8761660
TI  - [Alginates of Pseudomonas aeruginosa: a complex regulation of the pathway of
      biosynthesis].
AB  - Pseudomonas aeruginosa is an opportunistic pathogen causing severe infections,
      especially in lungs of patients with cystic fibrosis. Environmental conditions
      induce the production by the bacteria of a viscous mucoid exopolysaccharide,
      called alginate, which is one of the most important factor of virulence of P.
      aeruginosa. Alginate is a linear polymer of beta-1, 4-linked L-guluronic acid and
      D-mannuronic acid. The alginate biosynthetic pathway involves genes called alg
      which are clustered at the 34 min region of chromosomal DNA of P. aeruginosa. The
      key enzyme of alginate biosynthesis, the GDP-mannose dehydrogenase is encoded by
      the gene algD. Expression of algD is positively controlled by several proteins,
      especially AlgU, a putative sigma factor homologous to sigma E of E. coli, AlgR
      and AlgP, a transactivator and an histone-like respectively. Here, a scheme of
      alginate biosynthetic pathway and a model for the alg genes regulation are
      described from results published in literature and from our own interpretation.

PMID- 8761661
TI  - Pathways for conformational change in seryl-tRNA synthetase from Thermus
      thermophilus.
AB  - Seryl t-RNA synthetase of the bacterium Thermus thermophilus contains a long arm,
      consisting of an antiparallel coiled coil, that is involved in binding of tRNA.
      Two crystallographic structures exist for this protein, in which the arm is in
      different conformations. Here, we use computational methods employing an
      empirical potential energy function to investigate the flexibility of the long
      arm. A conformational pathway is calculated between the 2 crystallographic
      structures using a method based on molecular dynamics simulation. The pathway is
      analyzed in terms of sequential phi and psi backbone angle changes. Several
      transient phi and psi displacements are present along the pathway that are not
      visible in the end states and may be required for transition between them. Energy
      maps are constructed by rotating the arm around its principal axes of inertia and
      energy minimizing. The map identifies 2 regions of relatively low energy which
      might be accessible to the arm.

PMID- 8761662
TI  - Database cloning human delta 1-pyrroline-5-carboxylate synthetase (P5CS) cDNA: a
      bifunctional enzyme catalyzing the first 2 steps in proline biosynthesis.
AB  - delta 1-pyrroline-5-carboxylate synthetase (P5CS) catalyzes the ATP and the
      NAD(P)H-dependent conversion of L-glutamate to glutamic gamma-semialdehyde (GSA)
      which is the metabolic precursor for proline biosynthesis. We cloned a human P5CS
      cDNA by database cloning strategy and sequenced 2,907 bp from this cDNA which has
      a closed open reading frame (ORF) of 2,385 bp coding for a polypeptide of 795
      amino acid residues. This cDNA, as its plant counterpart, encodes a bifunctional
      enzyme, with both gamma-glutamyl kinase (gamma-GK) and gamma-glutamyl phosphate
      reductase (gamma-GPR) activities that catalyzes the first 2 steps in proline
      biosynthesis and it hybridizes to a 4.5 kb mRNA from various tissues. A human
      genetic disease caused by a deficient P5CS has been recognized. The phenotypic
      features for deficiency of P5CS include joint hyperlaxity, skin hyperelasticity,
      cataract and mental retardation with hyperammonemia and low plasma levels of
      proline, citrulline and ornithine.

PMID- 8761664
TI  - Ccl1, a cyclin associated with protein kinase Kin28, controls the phosphorylation
      of RNA polymerase II largest subunit and mRNA transcription.
AB  - The Kin28 protein kinase interacts physically and genetically with cyclin Ccl1.
      Kin28 has been reported recently to be involved in the in vivo phosphorylation of
      the largest subunit of RNA polymerase II (Rpb1) in Saccharomyces cerevisiae. Now,
      we show that in a strain harboring a conditional ccl1-ts mutation, the C-terminal
      domain (CTD) of the Rpb1 subunit is under-phosphorylated at restrictive
      temperature. The transcription of a set of genes, chosen at random, is severely
      affected in a kin28-ts mutant shifted at restrictive temperature. Here, we report
      that the same set of genes requires a functional CCL1 gene product to be
      transcribed. These findings, added to previously published data, establishes that
      Kin28p is a cyclin-dependent kinase (CDK) with Ccl1p as a companion, both of them
      being necessary for general transcription and CTD phosphorylation.

PMID- 8761663
TI  - Ku protein complex is involved in nucleotide excision repair of DNA.
AB  - The repair of UV-C (254 nm) DNA lesions by nucleotide excision repair (NER) has
      been studied in the rodent cell line xrs6 belonging to complementation group 5 of
      ionising radiation sensitive (IRs) mutants. xrs6 cell line shows a defect in the
      DNA-end binding protein complex Ku which is involved in the repair of double
      strand breaks (DSB) due to IR. In agreement with IR sensitivity, a bleomycin
      sensitive phenotype of xrs6 cell line was found as compared to the parental CHO
      K1 line (factor > 8 fold). xrs6 exhibited also a slight (factor 2) but
      reproducible sensitivity to UV-C-light, while a revertant cell line for Ku DNA
      end binding activity, xrs6rev, showed a restoration of both IR and UV-C
      sensitivities to the parental level. The NER activity of these cell lines was
      measured in vitro in nuclear protein extracts in the presence of plasmid DNA
      repair substrate damaged with UV-C lesions repaired by NER: xrs6 cell extracts
      exhibited only 55% of NER activity as compared to the control CHO-K1 and xrs6rev
      cell extracts. These results indicate that the Ku DSB repair protein is involved
      also in the NER process.

PMID- 8761665
TI  - [Voltametric detection of cerebral NO in rats. Variations of the signal
      throughout the sleep-wakefulness cycle].
AB  - Nitric oxide (NO) is synthesized in the neurons by constitutive NO synthase
      (NOS). Within given neuronal sets, this enzyme is colocalized with different
      other neurotransmitters such as, for example, GABA, acethylcholine or serotonin.
      Our attention has been focused on the fact that serotoninergic neurons, well
      known for their involvement in sleep triggering and maintenance, synthesize also
      NO. In order to evaluate the modalities of release of this compound throughout
      the rat sleep-waking cycle, we prepared a sensor allowing its specific detection
      in freely moving animals. The active part of this sensor is a carbon fiber (phi =
      30 microns) successively coated with porphyrin nickel and nafion. In vitro,
      together with differential normal pulse voltammetric measurements, it allows the
      detection of a 650 mV signal varying linearly in NO solutions ranging from 5.10(
      7) to 10(-4) M. At physiological concentrations, L-arginine, L-citrulline,
      nitrites and nitrates do not yield a signal at 650 mV. Similarly, the compounds
      administered to the animals, hydroxylamine, L-arginine p-nitroanilide (L-ANA) and
      L-N omega-nitro arginine methyl ester (L-NAME) are not electroactive at 650 mV. L
      ANA and L-NAME, also appear to be trapping agents for NO while leaving the
      electrochemical properties of the sensor untouched. In vivo, in the frontal
      cortex of the anesthetized rat, a signal is measured at 650 mV. The
      administration of hydroxylamine (40 mg/kg, i.p.) induces a 100% increase in its
      height. The administration of L-ANA (100 mg/kg, i.p.) produces its complete
      disappearance within 50 min. Finally, the administration of L-NAME (100 mg/kg,
      i.p.) is without effect. This last aspect might be dependent upon the inability
      of L-NAME to cross the blood brain barrier. On the contrary, the increase in the
      signal height obtained with hydroxylamine and its disappearance with L-ANA
      support that it might depend upon NO. In vivo, and in animals also equipped with
      polygraphic electrodes, the signal measured in the same area of the cortex
      exhibits the highest height during the waking state and decreases during either
      slow-wave sleep (-6%) or paradoxical sleep (-9%). These mild variations might
      represent the mean of several NO sources (cortical GABAergic interneurons,
      cholinergic and serotoninergic axonal nerve endings), each of them varying
      differently throughout the sleep-waking cycle.

PMID- 8761666
TI  - [Action duality of nitrogen oxide (NO) in experimental African trypanosomiasis].
AB  - Patients with human African trypanosomiasis present a major dysruption of the
      circadian rhythmicity of the sleep-wake cycle, which was also found in rats
      infected with Trypanosoma brucei brucei (T.b.b.). The alterations in the immune
      function and nervous system in African trypsanosomiasis led us to investigate the
      involvement of nitric oxide (NO), a key molecule in immune and neurophysiological
      mechanisms, in experimental trypanosomiasis. NO was measured in 35 Sprague Dawley
      rats using differential impulsional voltammetry with a carbon fiber coated with
      porphyrin-nickel and nafion, ex vivo in the blood and in vivo in the brain. The
      rats were anaesthetized with sodium chlorate. Infection was performed
      intraperitoneally (i.p.) with 0.2 ml of a T.b.b. cryostabilate (clone AnTat
      1.1E). Blood was collected by an intracardiac puncture with immediate replacement
      of blood volume (1 ml) in 7 control rats and 8 rats infected since 15 days,
      before and after i.p. administration of L-ANA (L-arginine-p-nitro-anilide, 100
      mg.kg-1, an inhibitor of NO synthase). Brain measures were done in 20 rats (8
      controls, and 12 rats infected since 15 or 21 days), in the cortex (H, -0.5 mm;
      AP, -0.8 mm; L, 1.2 mm) and the lateral ventricle (H,-3.2 mm). In infected rats,
      blood NO was at 70% of control values (p < 0.001), and L-ANA suppressed the NO
      signal in all animals (p < 0.0001), demonstrating that the signal originated from
      NO. Cortical NO was higher than in the ventricle in both control (p < 0.0001) and
      infected rats (p < 0.001). NO was more elevated in both structures in 15-day
      infected rats than in control rats (p < 0.0001), the difference being enhanced in
      21-day-infected rats (p < 0.001). L-ANA suppressed the NO signal in 30 to 60 min.
      These data suggest that NO intervenes in the development of trypanosomiasis in
      different manners. It is increased in the brain, which remains unexplained, where
      it may be involved in blood-brain barrier permeation. Conversely, it is decreased
      in the blood, may be because of macrophage function impairment, which would
      explain why trypanosomes can multiply in the host.

PMID- 8761667
TI  - [Reactive oxygen species and defense mechanisms in marine bivalves].
AB  - The main results published on the production of reactive oxygen intermediates by
      hemocytes and digestive glands of marine bivalves such as mussels, oysters or
      clams have been reviewed and discussed. Mussel and oyster hemocytes respond to
      appropriate stimuli with a burst of respiratory activity and the generation of
      reactive oxygen intermediates in a manner resembling the respiratory burst of
      mammalian phagocytes. However, interspecies differences in hemocytes-mediated
      antimicrobial defense mechanisms occur since clam hemocytes do not show any
      increase of reactive oxygen intermediate production upon similar stimulations.
      Hepatopancreatic gland of bivalves, as mammalian and fish liver produce reactive
      oxygen species during the one-electron reduction of xenobiotics, and mechanistic
      differences appear between bivalves and mammals. Thus, it appears that, in spite
      of some interspecies differences, the generation of cytotoxic reactive oxygen
      species is a general protective mechanism of most, if not all, animal species.

PMID- 8761668
TI  - [Open heart operation under videosurgery and minithoracotomy. First case (mitral
      valvuloplasty) operated with success].
AB  - The development of "less invasive surgery" using small incisions and videoscopic
      techniques may change, in the near future, our attitude towards "traditional"
      surgery. This is because of specific advantages such as skin limited incisions,
      reduced perioperative disability and lower cost. Up to now, only abdominal,
      thoracic and coronary artery surgery which do not imply the opening of the heart,
      or closure of simple atrial septal defects, have benefitted from this new
      approach. This article reports the first case of open heart surgery for complex
      lesions of the left heart through a minithoracotomy (5 x 4 cm) with the use of
      videotransmission and peripheral extracorporeal circulation. The patient, a 30
      year-old female, was operated upon for a combined mitral valve stenosis and
      insufficiency of rheumatic origin unsuccessfully treated by a previous
      percutaneous valve dilatation. The 2.5 h open heart procedure comprised
      commissurotomy, repair of torn leaflets, chordal transposition and Carpentier
      Edwards prosthetic ring implantation. The patient left the hospital 12 days after
      the operation. Transesophageal echocardiography at discharge showed normal valve
      function with no residual stenosis or residual leak.

PMID- 8761669
TI  - [Immigration of a pregnant female in an alpine marmot family group: behavioural
      and genetic data].
AB  - The acceptance of a pregnant female by the dominant male of a family group of
      alpine marmots (Marmota marmota) (population of La Grande Sassiere, Parc national
      de la Vanoise, French Alps) was revealed by the combined results from
      microsatellite polymorphism analysis and behavioural studies. These first results
      seem to indicate that the mating system of the alpine marmot is more complex than
      previously thought, that polygyny cannot be excluded, and that adult females can
      join neighbouring groups. This acceptance would have been interpreted as an extra
      pair fertilization if complete field data had not been available.

PMID- 8761670
TI  - [Europe and initial and continuing medical education in hepato-gastroenterology].

PMID- 8761671
TI  - [Development of safer liver surgery].

PMID- 8761672
TI  - [Limitation of blood transfusions during hepatectomies. Study of 150 consecutive
      hepatic resections on healthy and pathological livers].
AB  - OBJECTIVE: Over the last 5 years, a policy to limit blood transfusions has been
      adopted in patients undergoing liver resection. The aim of this retrospective
      study was to report the results of 150 liver resections performed during this
      period. METHODS: There were 63 major (42%) and 87 minor hepatectomies (58%).
      Resection was performed for malignant lesions in 64% of the patients. Vascular
      exclusion of the liver was used in large (> or = 10 cm) tumors and those located
      at the cavohepatic junction. Clamping of the portal triad or selective clamping
      of the pedicle of the portal lobe was used in peripheral lesions < 10 cm in
      diameter. Anesthesia was adapted to the type of vascular clamping and blood
      transfusions were deliberately limited. Red blood cells were transfused to
      maintain the hematocrit level above 25% in healthy patients and above 30% in
      patients with risk of coronary artery disease. RESULTS: Ninety three patients
      (62%) did not receive blood transfusions. Three patients received more than 10
      units of packed red blood cells (2%). 48% of patients with major hepatectomies
      and 72% with minor hepatectomies were not transfused. The rate of non transfused
      patients was 93% for benign lesions and 44% for malignant lesions. The presence
      of pathologic changes in non-tumor liver parenchyma did not influence the need
      for transfusions. Hospital mortality was 3% (5/150). There was no mortality in
      patients with normal non-tumorous livers, 14% in the presence of cirrhosis, and
      12% in the presence of obstructive jaundice or steatosis > 50%. The specific
      morbidity rate was 7% in patients with normal livers and 54% in patients with
      abnormal livers. CONCLUSION: This series shows that more than 60% of liver
      resections can be performed without blood transfusions. These results require an
      appropriate surgical technique and collaboration between anesthesiologist and
      surgeon. Thus hepatectomies in normal non-tumorous livers can be performed
      without mortality. In contrast, the presence of abnormalities of the non-tumorous
      liver parenchyma remains a major risk factor.

PMID- 8761673
TI  - [Imaging of peripheral cholangiocarcinoma. Comparison with pathological anatomy].
AB  - OBJECTIVE: Peripheral cholangiocarcinoma is a rare malignant intrahepatic tumor
      which originates in the distal bile duct. Our purpose was to identify the imaging
      characteristics of peripheral cholangiocarcinoma and to establish a correlation
      with surgical and histopathologic findings. METHODS AND MATERIALS: The imaging
      data of 16 patients with proven cholangiocarcinoma were retrospectively reviewed
      by sonography in 13 cases, computed tomography in 13 cases, magnetic resonance
      imaging in 6 cases, and angiography in 10 cases and correlated with surgical and
      histopathologic findings. RESULTS: In most cases peripheral cholangiocarcinoma
      appeared as a single, large (> 10 cm), heterogeneous, and non encapsulated mass.
      On precontrast computed tomography, the lesions were mostly low density.
      Enhancement was moderate in the bolus phase and increased in the delayed scan.
      With magnetic resonance imaging, lesion signals were low intensity in T1-weighted
      images and variable intensity in T2-weighted images. On angiogram, lesions were
      often hypovascular. Associated features were frequently observed: portal
      encasement (69%), lobar atrophy or capsular retraction (43%), dilated
      intrahepatic bile ducts (30%), extension into the hepatic capsule (23%), and
      inferior vena cava extension (15%). Radiopathologic comparison showed that
      imaging modalities accurately identified vascular encasement, but underestimated
      extrahepatic tumor extension. CONCLUSION: In most cases, peripheral
      cholangiocarcinoma has a typical appearance which may be helpful in
      differentiating this disease from other intrahepatic tumors.

PMID- 8761675
TI  - [Natural history of treated hemorrhagic rectocolitis].

PMID- 8761674
TI  - [Biological diagnosis of hepatitis C virus infection. Role of serological and
      molecular tests].

PMID- 8761676
TI  - [Prognosis in pancolonic forms of hemorrhagic rectocolitis].
AB  - OBJECTIVE: To assess the prognosis of pancolitis in ulcerative colitis including
      survival, colectomy rate, colon cancer risk, activity of disease, functional and
      socioprofessional impact. METHODS: Retrospective study of 130 cases of ulcerative
      pancolitis referred consecutively to Rothschild Hospital from 1962 to 1993. They
      were 58 men and 72 women. The mean age at onset of ulcerative colitis was 30
      years (range: 5-77). The extension to the right colon was secondary in 68% of
      patients. The period of observation ranged from 0.8 year to 46 years from the
      onset, with a median of 10.6 years. Three patients were lost to follow up.
      RESULTS: Eight patients died, the survival rate being 93% at 10 years. Surgical
      treatment was performed in 85 patients. The cumulative colectomy rates were 61%
      and 77% at 10 and 20 years respectively. Colonic cancer developed in three
      patients, corresponding to a cumulative risk after 25 years of 6% in unoperated
      patients and 1.9% in the whole series. No cancer occurred after colectomy and
      ileorectal anastomosis. In the group of unoperated patients there was a decrease
      of activity of the disease during the first fifteen years. The quality of life of
      colectomized patients with reestablishment of intestinal continuity and of those
      treated conservatively did not differ significantly. CONCLUSION: In this series,
      long term prognosis of ulcerative pancolitis was favourable. The high colectomy
      rate was balanced by a very low risk of colorectal cancer.

PMID- 8761677
TI  - [Sacral rectopexy-sigmoidectomy in the treatment of rectal prolapse syndrome.
      Anatomical and functional results].
AB  - Various options have been suggested to improve the functional results of
      abdominal rectopexy for rectal prolapse and to limit the risk of post-operative
      constipation. OBJECTIVES: In this prospective study, we evaluated the results of
      posterior abdominal rectopexy-sigmoidectomy to treat rectal prolapse syndrome in
      terms of morbidity, anatomic correction and bowel function. Patient benefits
      after surgery were assessed according to their pre-operative functional status.
      PATIENTS AND METHODS: Twenty patients (14 females, mean age: 42 years) were
      treated for rectal prolapse with sutured abdominal rectopexy and sigmoidectomy.
      RESULTS: (a) Thirteen patients had normal post-operative course. No anastomotic
      leak occurred. Mean hospital stay was 9.7 days. (b) Anatomical control was
      obtained in all cases for a mean follow-up of 31.2 months without recurrence. (c)
      Functional results: bowel movements per week remained unchanged pre- and post
      operatively (18.6 +/- 33 vs 18.1 +/- 17). Constipation appeared or worsened in 2
      patients (10%). Anal incontinence (n = 6-30%) never worsened post-operatively and
      improved in 3. CONCLUSIONS: This prospective clinical study confirmed the
      important functional disorders occurring in rectal prolapse syndrome. Rectopexy
      sigmoidectomy is a valid option with stable mid-term results. Constipation was
      observed in 10% with no worsening of anal incontinence.

PMID- 8761678
TI  - Putrescine transport in differentiated Caco-2 cells.
AB  - OBJECTIVE AND METHODS: To evaluate the putative importance of digestive luminal
      polyamines, we investigated the role of oxidation in putrescine uptake and
      transport in differentiated Caco-2 cells grown in monolayer. RESULTS: Our results
      confirm a putrescine uptake system located both at the apical and basolateral
      cell membrane. Putrescine is efficiently transported and excreted in the apical
      to-basolateral direction. CONCLUSION: These results suggest (i) a diamine oxidase
      controlled catabolic oxidative excreting pathway and (ii) a paracellular route
      for putrescine transport. This catabolic route seems to proceed by converting
      putrescine into gamma-aminobutyraldehyde which is then rapidly excreted from the
      cell at the basolateral membrane since no gamma-aminobutryraldehyde was detected
      in the cell. This putative basolateral excreting mechanism is inhibited in the
      presence of the diamine oxidase inhibitor, aminoguanidine.

PMID- 8761679
TI  - [Collagens in intestinal smooth muscles].

PMID- 8761680
TI  - [Liver abscess caused by Lactobacillus acidophilus].
AB  - Lactobacillus acidophilus is usually considered to be non pathogenic. We report a
      case of liver abscess due to Lactobacillus acidophilus in a 39 year-old man with
      chronic pancreatitis complicated by both endocrine and exocrine insufficiency,
      and with a choledoco-duodenostomy. Lactobacillus acidophilus was isolated in
      blood and liver samples. Complete recovery of the liver abscess occurred after
      antibiotherapy. We suggest that the abnormally low duodenal pH secondary to
      pancreatic insufficiency may have promoted both Lactobacillus acidophilus
      adhesion and multiplication in this patient. The choledoco-duodenostomy may then
      have promoted biliary tract colonisation.

PMID- 8761681
TI  - [Budd-Chiari syndrome secondary to post-traumatic stenosis of the inferior vena
      cava].
AB  - Budd-Chiari syndrome with inferior vena cava involvement is usually due to
      membranous obstruction; traumatic origin of inferior vena cava lesions is very
      rare. We report a case of Budd-Chiari syndrome in a 29 year-old man, 3 years
      after an abdominal trauma. Cavography showed 50% stenosis in the sushepatic
      portion of the inferior vena cava. After two unsuccessful percutaneous
      transluminal angioplasty procedures, a surgical resection of the stenotic vein
      was performed. The histological study of the stenotic segments showed that the
      three layers of the venous wall had been replaced by a dense fibrous tissue. No
      inflammation or thrombosis were found. This case of stenosis of the vena cava
      shows that histological examination can be used to assess the traumatic nature of
      the lesion, showing a different histological pattern from that of the membranous
      obstruction in which the basic structure of the venous wall is preserved.

PMID- 8761682
TI  - [Gastric duplication or pancreatic pseudocyst. Diagnostic difficulties apropos of
      a case].
AB  - Gastric duplication was diagnosed in a 50 year-old patient who was initially
      thought to have a pancreatic pseudo-cyst until laparotomy was performed. There
      are many clinical and radiological similarities between gastric duplication and
      pancreatic pseudo-cyst. However, the following elements can suggest the diagnosis
      of gastric duplication in the case of the discovery of a cystic mass in the
      gastric or pancreatic area: normal pancreatic enzyme levels, ultrasonic
      identification of a hyperechoic inner rim and a hypoechoic outer rim with
      peristaltic movements into the cyst, visualization of a communication between the
      cyst and the gastro-intestinal tract, and detection of associated vertebral
      abnormalities. Surgical treatment of gastric duplication is only necessary in
      symptomatic cases.

PMID- 8761683
TI  - [Increase of alpha-fetoprotein in pancreatic endocrine tumors with hepatic
      metastases. Apropos of 2 cases].
AB  - We report two cases of metastatic non-functioning pancreatic endocrine tumour
      with very elevated plasma levels of alpha-fetoprotein. In these two cases, serial
      plasma levels of alpha-fetoprotein, initially normal, correlated well with
      hepatic tumour progression and were associated with fatal outcome. These results
      suggest that elevated plasma concentration of alpha-fetoprotein may be caused by
      metastatic pancreatic endocrine tumour and than alpha-fetoprotein serial
      measurement may be useful in prognostic evaluation.

PMID- 8761684
TI  - [Dermatological manifestations of Alagille syndrome].

PMID- 8761685
TI  - [An unusual cause of hemoperitoneum: hemocholecyst and rupture of the gallbladder
      secondary to the ulceration of an artery caused by a gallstone].

PMID- 8761686
TI  - [Acute viral hepatitis E in the Poitou-Charentes region].

PMID- 8761687
TI  - [Pure angiocholitic form of congenital hepatic fibrosis].

PMID- 8761688
TI  - [Spontaneously regressive liver abscess caused by Yersinia enterocolitica
      revealing genetic hemochromatosis: a second case].

PMID- 8761689
TI  - [Acute hemorrhagic colitis induced by glutaraldehyde after colonoscopy].

PMID- 8761690
TI  - [Proctitis after colonoscopy: importance of rinsing the colonoscope!].

PMID- 8761691
TI  - [Acute respiratory distress syndrome with fatal outcome after inhalation of
      polyethylene glycol during preparation for colonoscopy].

PMID- 8761692
TI  - [Hemopneumoperitoneum: a rare complication after endoscopic polypectomy].

PMID- 8761693
TI  - [Annular pancreas: ultrasound endoscopy too].

PMID- 8761694
TI  - [Polyarticular pain syndrome during treatment with cyclosporine for severe acute
      colitis].

PMID- 8761695
TI  - [Treatment of hepatocellular carcinoma with tamoxifen].

PMID- 8761696
TI  - [Risk of laparoscopic surgery. 100 records of complications. A qualitative
      study].
AB  - A total of 100 accidents occurring during laparoscopic surgery between 1969 and
      1993 were studied. Fifty-five of the cases concerned gynaecology surgery over a
      24 year period. The other 45 concerned digestive surgery over a 5 year period
      (1989-1993). The surgical risk was not statistically greater compared with open
      surgery. Overall morbidity was 1%. Overall mortality was 0.5/1000. A more precise
      statistical analysis was recently reported. The examination of the 100 cases was
      qualitative rather than quantitative. The study demonstrated an imbalance between
      age (mean age 38 years) in patients with major pathology initially and the
      gravity of the induced accidents: 26 deaths for 100 observations. These deaths
      were related to technology trocar, capnoperitoneum, electrocoagulation. Technical
      skill, cautiousness, vigilance and humility are qualities the surgeon must have
      to perform successful operations. The irreversible acceleration of the new
      surgical technique should not cloud the basic precepts of sound surgical
      technique.

PMID- 8761697
TI  - [Film presentation. Nissen's fundoplication under video-laparoscopy].

PMID- 8761699
TI  - [Laparoscopic cholecystectomy in obese patients: 110 cases].
AB  - 110 obese patients who underwent a laparoscopic cholecystectomy were compared
      with a group of controls, the operative time (108 mn), the conversion rate to
      laparotomy (4.5% vs 1.8%) and the incidence of drainage (26 vs 11%) were
      significantly raised in the obese patients. However there was no difference in
      the mortality (0), the feasibility of intraoperative cholangiography, the
      hospital stay, the morbidity or the time off work when compared with the
      controls. In particular the incidence of wound infections, thromboembolic or
      respiratory complications (frequent in conventional surgery on the obese) was not
      significantly different to the control group operated on laparoscopically. This
      study supports that laparoscopic approach is an elective procedure for obese
      patients.

PMID- 8761698
TI  - [Diffuse gastric angiomatosis. A clinical case. Review of the literature].
AB  - Stomach angiomatosis is a rare disease. We report an exceptional case of diffuse
      gastric angiomatosis complicated with severe bleeding; the patient underwent two
      operations for dramatic haemorrhage with shock. Selective arteriography provided
      the diagnosis. Total gastrectomy was performed in a third operation providing
      remission with a 3 year follow-up. The diagnosis of gastric angiomatosis is
      difficult and is essentially based on the fundamental selective angiography.
      Histology examination confirms the diagnosis and demonstrates vascular
      malformations. Cases reported in the literature are usually isolated cases: 47
      angiomatoses of the stomach have been reported. Treatment is always surgical with
      gastrectomy providing complete remission. This case report demonstrates the need
      for a revision of the classifications of vascular tumours of the stomach.

PMID- 8761700
TI  - [Surgical activity at the military health service antenna during the Turquoise
      operation in Rwanda June-August 1994].
AB  - The military health service provided a surgery antenna during the two months of
      the Turquoise operation in Zaire and Rwanda. During this period, the antenna
      functioned as a back-up station for the French troop and the local populations
      subjected to various conditions: Rwanda refugees who had escaped the massacres,
      subjects wounded by canon shots, war wounds, surgery emergencies in the refugee
      population. There were 315 operations performed including 33% in children and 70%
      for lesions of the limbs. The activity during the mission was analyzed on the
      basis of strategy for surgical diagnosis and treatment under local conditions
      (lack of complementary examinations, limited number of personnel, disrupted
      families in the refugee population, no possibility for transfer, major cholera
      and dysentery epidemic...).

PMID- 8761701
TI  - [Oncocytic cancers of the thyroid. Hurthle cell cancers].
AB  - Hurthle cell cancers of the thyroid have been a subject of debate for many years
      because it is difficult to differentiate between benign and malignant tumours.
      Diverse therapeutic strategies have thus ensued. Recent work describing the
      morphologic and biologic criteria for a more precise diagnosis have led to better
      therapeutic strategies. We report a series of 85 tumours of the thyroid with
      Hurthle cells including 19 Hurthle cell tumours (22%) operated between 1976 and
      1994. Hurthle cell tumour represented 6.7% of 282 thyroid cancers operated during
      the same period. The mean age of the patients was 56.6 years (range 23 to 78
      years) and 63% of the tumours were large > or = 4 cm (classed T3T4). Treatment
      was total thyroidectomy in 79% of the cases. 5-year survival was 58.3% and 25% of
      the cases had metastatic extension at the time of initial treatment. Hurthle cell
      cancer have now been recognized as a particular anatomic and clinical entity.
      They were formerly confounded with vesicular cell cancers but now have been
      separated into a single entity due to a poor prognosis, lack of response to
      radioactive iodine and high incidence of metastasis. The current histological
      criteria make diagnosis more precise and allow more logical treatment with total
      thyroidectomy. A few familial cases have been reported. Although less frequent
      than in medullary cancer, this form would suggest that a genetic survey should be
      conducted for this particular type of thyroid cancer.

PMID- 8761702
TI  - [Treatment of breast cancer located behind the nipple with musculocutaneous flap
      from the latissimus dorsi. 1. Technical aspects].
AB  - The aim of this work is to present a conservative technique of breast
      retroareolar cancer. After whole excision of nipple areola area, reconstruction
      is immediately performed by transposition of a myocutaneous latissimus dorsi
      flap. After local radiotherapy, a new areola and nipple can then be made a few
      months later.

PMID- 8761703
TI  - [Treatment of breast cancer located behind the nipple with musculocutaneous flap
      from the latissimus dorsi. 2) Analysis of a series of 14 cases].
AB  - The authors report a series of 14 cases of retroareolar breast cancer treated by
      wide excision followed by reconstruction with latissimus dorsi flap. Based on
      clinical and histological datas, they establish surgical indications and show
      that this procedure can be used for central tumors whose diameter goes from 1.5
      to 3 cm even if the nipple is retracted. Cosmetical and functional results are
      usually goods. They just have to note one infection medically treated.

PMID- 8761704
TI  - [Pediculated anterior graft for reducing necrosis of the femur head in femoral
      neck fractures].
AB  - This article in addition of reviewing the current techniques of surgical
      treatment of femoral neck fractures, also presents a newly devised technique, in
      which by anterior approach the pediculated muscle bone graft from the anterior
      part of the greater trochanter with attached gluteus medius insertion is placed
      at anterosuperior part of the fractured femoral neck (type 3 & 4 Garden and old
      neglected fractures). This paper reviews the older techniques of Judet and Meyer
      in which the pediculated bone graft is taken from quadratus femoris insersion and
      placed posteriorly to the femoral neck which may compromise the important
      vascular supply (posterior subsynovial retinacular artery) posteriorly to the
      neck. The new anterior technique has been used for 20 patients successfully for
      the first time in department of orthopaedic surgery in Imam Reza Medical Center.
      In Mashhad-Iran from 21/3/93. The ultimate analysis of results will be possible 3
      years after operation.

PMID- 8761705
TI  - [Use of prostheses in emergency surgery. Retrospective study of 204 strangulated
      inguinal hernias].

PMID- 8761706
TI  - [Incidents and complications of therapeutic thoracoscopy. Apropos of 898 operated
      patients].
AB  - The exceptional interest in endoscopic surgery, both in laparoscopic surgery and
      video-assisted thoracoscopic surgery have led many teams to widen their
      indications. This movement has developed into a revolution in techniques demanded
      by patients, the public, and the medias, requiring many practicians to use these
      techniques more and more often and consequently to attempt very delicate
      operations. This "explosion" of endoscopic techniques has largely benefited from
      advances in equipment development (optics, video instrumentation) but has also
      required that operators acquire rigorous procedures for the proposed techniques.
      With the development of new thoracoscopic techniques for therapeutic indications,
      there are an unavoidable number of incidents and complications. These incidents
      and complications are related both to the use of instruments undoubtedly not well
      enough adapted to the procedures used and also to "forced" indications. We humbly
      recognize that a certain number of incidents are related to the necessarily
      inadequate experience of the operators during the "run in" period. We emphasize
      that video-assisted thoracoscopic surgery is a complementary technique among the
      available therapeutic armamentarium. We evaluated the mid and long term results
      of cancerology exeresis with these two techniques and underscore that morbidity
      and complications are rare but sometimes unacceptable. In conclusion, whatever
      the form of the technique used, it is an important evolution in surgery which
      must abide by the classical rules, in particular for indications in cancer
      surgery.

PMID- 8761707
TI  - [Ultrasound-guided percutaneous drainage in the treatment of retentional
      pseudocysts of chronic pancreatitis].
AB  - 25 to 35% of the patients with calculous chronic pancreatitis will develop a
      pseudocyst in the course of their disease. Up to recent years pancreatic
      pseudocysts were treated surgically most of the time by internal drainage (cysto
      jejunostomy). More recently, it was proved that percutaneous drainage could
      collapse pseudocysts if aspiration was maintained within 3 to 4 weeks. From
      January 1986 to December 1994, 22 patients with Wirsung communicating pseudocysts
      were treated percutaneously. Total recovery was achieved in 11 patients (50%). In
      these cases the pancreatic out flow towards the duodenum was always restored.
      There were 8 recurrences, always in relation with persistent or recurrent
      obstruction of the pancreatic main duct. Modern procedures, associating extra
      corporal lithotripsy and transpapillary endoscopic management should allow to
      reduce the failure rate of percutaneous drainage. According to their results, the
      authors state that an unuseful operation can be avoided in 50% of the patients
      with percutaneous drainage only. This success rate could probably be increased
      with association of other non invasive procedures aiming at the permeability of
      pancreatic duct.

PMID- 8761708
TI  - Ophthalmoplegic migraine.
AB  - Ophthalmoplegic migraine is a rare condition usually beginning in infancy or
      childhood and characterized by paralysis of ocular cranial nerves in association
      with vascular headache. The diagnosis is one of exclusion. Most patients should
      have high resolution magnetic resonance imaging (MRI) or magnetic resonance
      angiography (MRA) to eliminate the possibility of aneurysm, tumor, or
      granulomatous inflammation.

PMID- 8761709
TI  - Behavioral management of migraine.
AB  - Behavioral treatments for migraine have received increased attention over the
      past 25 years. In general, research has focussed on the six following areas: 1)
      comparative efficacy of treatments, 2) interplay of behavioral and
      pharmacological approaches, 3) development of delivery models that are cost
      effective, 4) identification of characteristics associated with varied levels of
      response to treatment, 5) maintenance of effects and factors associated with long
      term outcome, and 6) mechanisms of treatment. This paper briefly and selectively
      reviews the available literature in an attempt to point out the status of current
      research.

PMID- 8761710
TI  - Psychological treatments for migraine.
AB  - Psychological and behavioral treatments for migraine are described and evidence
      for their efficacy is reviewed. Treatments for children, adolescents, and the
      elderly, and for menstrual migraine are then discussed. Biofeedback, relaxation,
      and stress-coping treatments have all demonstrated effectiveness. These
      treatments are effective for the majority of migraine sufferers and treatment
      effects are reliably maintained for periods of at least one year. Little is known
      about the mechanism behind the efficacy of psychological treatments. Suggestions
      for future research on treatment mechanisms, enhancement of treatment
      effectiveness, and increasing the acceptance of psychological treatments are
      provided.

PMID- 8761711
TI  - Immunological aspects of migraine.
AB  - The physiopathology of migraine is still largely unknown. The author reviews the
      changes of immunoglobulins (especially IgE), complement fractions, mediators,
      cytokines and inflammatory cells published in the literature. An IgE mechanism
      seems to be unimportant in the process of food-induced migraine. Increasing
      arguments for the reciprocal modulation of the brain and immune system are also
      reviewed as the close links between interleukins and the sensory neuromediators.
      However, it is presently too early to implicate a definite immunological
      mechanism in the physiopathogeny of migraine.

PMID- 8761712
TI  - Deficient habituation of evoked cortical potentials in migraine: a link between
      brain biology, behavior and trigeminovascular activation?
AB  - According to recent evoked potential studies, a fundamental, probably protective,
      feature of cortical information processing, ie, response habituation during
      stimulus repetition, is abnormal in migraine between attacks. The deficient
      habituation is found for different sensory modalities and experimental paradigms:
      pattern-reversal visual evoked potentials (same stimulus at a constant
      intensity), cortical auditory evoked potentials (same stimulus at increasing
      intensities) and auditory event-related potentials obtained in a passive
      "oddball" paradigm (novel stimulus). The abnormal information processing is an
      interictal cortical dysfunction most likely due to inadequate control by the so
      called "state-setting, chemically-addressed pathways" originating in the brain
      stem, in particular by the serotonergic pathway, leading to a low preactivation
      level of sensory cortices. We suggest that it may play a pivotal role in migraine
      pathogenesis in conjunction with the reported decrease of brain mitochondrial
      energy reserve, by favouring a rupture of metabolic homeostasis and biochemical
      shifts capable of activating the trigeminovascular system and thus capable of
      producing a migraine attack. We postulate that both the deficient habituation in
      information processing and the deranged oxygen metabolism may have behavioral
      correlates. Which of these abnormalities are inherited, acquired or both remains
      to be determined.

PMID- 8761713
TI  - Lysosomal exocytosis induced by hyperthermia: a new model of cancer death. III.
      Effect on liver metastasis.
AB  - The purpose of the present study was to evaluate by morphological approaches
      (light and electron microscopy), the effect of hyperthermic treatment in one case
      of human liver metastasis. The results demonstrate that hyperthermia causes a
      significant reduction of the metastatic cells circulating into sinusoids and the
      "normalization" of the hepatocytes substructure. The data are consistent with a
      direct and/or indirect action of the temperature on the presence of infiltrating
      tumor cells. Particular importance is attributed to a general activation of
      lysosomes present in neoplastic cells, Kupffer cells and hepatocytes.

PMID- 8761714
TI  - Suppressive effect of met-enkephalin on bone marrow cell proliferation in vitro
      shows circadian pattern and depends on the presence of adherent accessory cells.
AB  - The cellularity of femoral bone marrow and the content of the granulocyte
      macrophage colony forming cells (GM-CFC) were followed in mice between 0600 h and
      1800 h. The cellularity increased at the beginning of the light period, and the
      GM-CFC content at the end. Opioid pentapeptide methionine-enkephalin reduced the
      GM colony forming ability of the bone marrow cell suspensions in proportion to
      the GM-CFC content. Removal of the accessory cells reversed the enkephalin
      sensitivity pattern of the GM-CFC. The circadian variations have been ascribed to
      a neuroendocrine regulatory network involving the opioid peptides and affecting
      the bone marrow accessory cells. The work draws attention to the circadian
      activity pattern of hemoregulatory oligopeptides applicable as adjuvants to
      antineoplastic chemotherapy.

PMID- 8761715
TI  - Solving the dilemma of antimycobacterial chemotherapy.

PMID- 8761716
TI  - Current problems with tuberculosis treatment.

PMID- 8761717
TI  - Treatment of disseminated Mycobacterium avium complex disease: a clinician's
      perspective.

PMID- 8761718
TI  - Clinical and epidemiologic implications of polyclonal infection due to
      Mycobacterium avium complex.

PMID- 8761719
TI  - Treatment of infections caused by rapidly growing mycobacteria in the era of the
      newer macrolides.

PMID- 8761720
TI  - The structure and function of the isoniazid target in M. tuberculosis.

PMID- 8761721
TI  - Action of clofazimine on the Mycobacterium avium complex.

PMID- 8761722
TI  - Rifamycin resistance in mycobacteria.

PMID- 8761723
TI  - Resistance to quinolones in mycobacteria.

PMID- 8761724
TI  - Ribosomal drug resistance in mycobacteria.

PMID- 8761725
TI  - The genetics of multiple drug resistance in Mycobacterium tuberculosis and the
      Mycobacterium avium complex.

PMID- 8761726
TI  - Novel strategies for the detection of drug resistance in Mycobacterium
      tuberculosis.

PMID- 8761727
TI  - Rapid measurement of antimycobacterial drug activity.

PMID- 8761728
TI  - Antimycobacterial quinolones: a comparative analysis of structure-activity and
      structure-cytotoxicity relationships.

PMID- 8761730
TI  - Glycosyltransferases as targets for inhibition of cell wall synthesis in M.
      tuberculosis and M. avium.

PMID- 8761729
TI  - Identification of new drug targets in Mycobacterium avium and Mycobacterium
      tuberculosis.

PMID- 8761731
TI  - sigma54-dependent transcription of the Pseudomonas putida xylS operon is
      influenced by the IIANtr protein of the phosphotransferase system in Escherichia
      coli.
AB  - IIANtr, encoded within the rpoN operons of many Gram-negative bacteria, is a
      homologue of a class of phosphoryl transfer proteins of the phosphoenolpyruvate:
      sugar phosphotransferase system. We have used a xylS operon-lacZ fusion from the
      TOL plasmid of Pseudomonas putida to show that IIANtr influences sigma 54
      dependent transcription when the xylS operon is expressed in Escherichia coli.
      Loss of IIANtr influences, but does not abolish cyclic AMP-independent carbon
      catabolite repression.

PMID- 8761732
TI  - Characterization of the plasmid pMB1 from Bifidobacterium longum and its use for
      shuttle vector construction.
AB  - The nucleotide sequence of the 1847-bp Bifidobacterium longum B2577 cryptic
      plasmid pMB1 was determined. The plasmid had a G+C content of 62.0%, and
      contained two open reading frames, orf1 and orf2, likely arranged in an operon.
      The proteins encoded by orf1 and orf2 show the highest degree of similarity with
      similarly arranged peptide sequences translated from Corynebacterium glutamicum
      pXZ10142 and Mycobacterium fortuitum pAL5000 plasmids. Recombinant plasmids
      containing the pMB1 replicon were able to replicate in Bifidobacterium animalis
      MB209. The successful transformation of this strain with pMB1-based plasmids
      facilitated characterization of this replicon, results of which showed that both
      orf1 and orf2 are necessary for plasmid replication. A family of new Escherichia
      coli-B. animalis shuttle plasmids, based on the pMB1 replicon and expressing a
      cat and an ery gene, was constructed.

PMID- 8761733
TI  - Overproduction of the Brucella melitensis heat shock protein DnaK in Escherichia
      coli and its localization by use of specific monoclonal antibodies in B.
      melitensis cells and fractions.
AB  - The Brucella melitensis dnaK gene was amplified by the polymerase chain reaction
      using primers chosen according to the published sequence of B. ovis and cloned in
      multiple copy plasmids enabling expression under the control of the Plac
      promoter. Monoclonal antibodies (mAb) obtained by immunizing mice with B.
      melitensis B115 cell wall (CW) fraction or by infecting mice with virulent B.
      melitensis strain H38 and recognizing a 73-kDa band in immunoblotting of the B.
      melitensis CW fraction reacted with the cloned dnaK gene product and were thus
      shown to be specific for the heat shock protein DnaK. The anti-Dnak protein mAbs
      did not react with Escherichia coli control cells or cell lysates and could
      therefore be specific to Brucella DnaK protein epitopes. These mAbs were further
      used to study overproduction of the DnaK protein. B. melitensis DnaK
      overproduction in E. coli resulted in a defect in cell septation and formation of
      cell filaments. Immunogold labelling with the mAbs and electron microscopy
      localized the DnaK protein inside as well as outside the E. coli cells, probably
      resulting from lysis due to toxicity of the overproduced DnaK protein. These
      results indicated that overproduction of the B. melitensis DnaK protein in E.
      coli had similar physiological consequences as that of E. coli overproduced in E.
      coli. The DnaK protein localization in B. melitensis cells was essentially
      cytoplasmic, as shown by immunoelectron microscopy. Heat shock treatment of these
      cells resulted in increased binding of mAbs and labelling in the cytoplasm.
      However, in subcellular fractions the DnaK protein was predominantly found in the
      cell envelope fraction of B. melitensis, which could perhaps be due to
      interaction of the DnaK protein with membrane proteins.

PMID- 8761734
TI  - Effect of thiosulphate as electron acceptor on glucose and xylose oxidation by
      Thermoanaerobacter finnii and a Thermoanaerobacter sp. isolated from oil field
      water.
AB  - During glucose and xylose fermentation, Thermoanaerobacter finnii was observed to
      produce lactate, acetate, H2 and CO2, with ethanol being the major end product.
      Thermoanaerobacter strain SEBR 5268, an isolate from an oil field, also produced
      a similar range of end products from glucose and xylose fermentation, with the
      exception that both ethanol and lactate were the major products of sugar
      metabolism. Both these strains were able to reduce thiosulphate to sulphide in
      the presence of these two substrates, with acetate being the dominant metabolite
      in that case. In addition, a faster growth rate and increased cell yield were
      obtained in the presence of thiosulphate, than in its absence. The higher
      concentrations of acetate produced in the presence of thiosulphate rather than
      without any electron acceptor indicated that more ATP was generated from
      substrate-level phosphorylation. These results have implications for our
      understanding of the breakdown of carbohydrates present in organic matter found
      in the natural ecological niches of Thermoanaerobacter species (sulphide-,
      elemental sulphur- or sulphate-rich thermal hot springs and oil fields).

PMID- 8761735
TI  - Study of a melanic pigment of Proteus mirabilis.
AB  - The present study sought to determine whether the pigment produced by Proteus
      mirabilis from the L-forms of various aromatic amino acids under aerobic
      conditions is melanic in nature. It is a black-brown pigment which behaves like a
      melanin in many respects, namely solubility features, bleaching by oxidizing
      agents and positive response to the Fontana-Masson assay. In the present study,
      for the first time, it was shown by electron spin resonance analysis that a
      bacterial melanin is able to act as a free radical trap, as was previously
      demonstrated for other melanins. Scanning electron microscopy studies showed a
      specific organized structure of the pigment as rounded aggregates of spherical
      bodies. DNA hybridization data did not reveal, in the P. mirabilis genome, any
      nucleotide sequence related to Shewanella colwelliana mel A, one of the two
      melanogenesis systems already defined at the molecular level in bacteria. Results
      obtained from experiments on pigment production inhibition suggest a possible
      role of tyrosinase in P. mirabilis melanogenesis. In conclusion, from the bulk of
      our results, it appears that the pigment produced by P. mirabilis is melanic in
      nature.

PMID- 8761736
TI  - Characterization of enterotoxigenic Escherichia coli by random amplification of
      polymorphic DNA.
AB  - Two enterotoxigenic Escherichia coli (ETEC) strains (H10407 and 4011-1) were
      characterized by random amplification of polymorphic DNA (RAPD) profiles using 10
      mer oligonucleotides with diverse GC content. All tested primers yielded arrays
      of amplified DNA products ranging in size from 200 to 3000 bp. The effects of
      annealing temperature, template concentration and GC content of the primers were
      evaluated and an optimal reaction procedure was established. Application of the
      RAPD analysis to ten ETEC strains belonging to five different serotypes showed
      that strains of the same serotype shared identical or almost identical band
      profiles, suggesting a similar genetic composition. The use of RAPD profiles as a
      tool in epidemiological analysis of ETEC is discussed.

PMID- 8761737
TI  - Ribosomal DNA polymorphism in the genus Bifidobacterium.
AB  - Ribosomal DNA polymorphism was studied in order to demonstrate intra- and
      interspecies differentiation of 42 Bifidobacterium strains. DNA from these
      strains was digested with the endonucleases BamHI, EcoRV, HindIII and PvuII and
      then analysed by Southern blotting. Ribosomal patterns using a part of an rRNA
      23S gene as a probe clearly differentiated the majority of species from each
      other. Only B. indicum ATCC 25912T and B. infantis ATCC 15697T displayed
      identical ribosomal patterns, even though they are classified into two different
      species. Moreover, ribotypes were able to distinguish between strains belonging
      to the same species. Furthermore, these strains generally showed common bands,
      except for B. infantis strains and two strains of B. animalis.

PMID- 8761738
TI  - Identification of spore-forming strains involved in biodegradation of
      acifluorfen.
AB  - We isolated and identified four spore-forming bacteria from activated sludges and
      soil, three of which were able to degrade acifluorfen. Biochemical
      characteristics, DNA base composition and DNA-DNA homology indicated that the
      degrading strains belonged to the species Bacillus thuringiensis, Clostridium
      perfringens and Clostridium sphenoides. The fourth strain, identified as C.
      sphenoides and showing the same characteristics of the corresponding degrading
      strain, was unable to metabolize acifluorfen. Thus, the plasmid content of these
      strains was analysed to study the possible correlation between the presence of
      extrachromosomal elements and the ability to degrade this herbicide.

PMID- 8761740
TI  - [Is magnetic resonance the first indication in neurologic imaging?].
AB  - Various methods of neuroradiologie examination are described, with an emphasis on
      recent developments, in particular in CT scan (angioscan, spiral acquisition) and
      MRI. CT scan, which is the most accessible method, can answer most questions in
      intracerebral emergencies (trauma, vascular accidents, intracerebral hypertension
      ...). Outside the emergency setting, morphological study of the brain by MRI is
      much superior to that provided by CT scan and should be the first-line
      examination for investigation of suspected tumour, wite matter lesion.... This is
      even more evident in exploration of lesions of the posterior cranial fossa. In
      addition, introduction in the near future of functional MRI should lead to better
      knowledge of the relationship between cerebral lesions and functional zones.
      Ultrasonography remains a noninvasive and effective technique to seek lesions of
      the arteries supplying the brain. For spinal cord disorders, MRI is by far the
      examination of choice, except when contraindicated by the presence of cardiac
      pacemaker, metallic foreign bodies in the patient.

PMID- 8761739
TI  - [From nuclear magnetic resonance to magnetic resonance imaging].
AB  - Magnetic resonance imaging is based upon the phenomenon of nuclear magnetic
      resonance. The patient is placed in a magnet the provides a strong magnetic field
      inducing a net magnetization due to hydrogen nuclei inside biological tissues.
      The image is formed from the localized measurement of this magnetization by means
      of radio-frequency waves. The contrast is a function of the number of hydrogen
      nuclei and of the time characteristics T1 and T2 of the return to equilibrium.
      Many other parameters can be measured by this method and the permanent
      improvement of the technique will extend further the field of its medical
      application.

PMID- 8761741
TI  - [Role of magnetic resonance imaging in liver pathology].
AB  - The increasingly common use of ultrasound examination of the liver has led to
      increased detection of hepatic tumours, showing a hitherto unsuspected
      prevalence. Improved techniques in MRI, such as dynamic sequences and new
      contrast media, are ameliorating the detection and characterization of the
      lesions, in particular with regard to computed tomography. In addition, since MRI
      is more sensitive to different components than in computed tomography, it permits
      better study of diffuse diseases such as haemochromatosis or fatty infiltration,
      particularly in pseudotumoural forms. The continuing progress in system
      improvement makes MRI an excellent method for diagnosis of bile duct disorders,
      especially in case of obstruction.

PMID- 8761742
TI  - [Magnetic resonance imaging of the locomotor apparatus].
AB  - A multiplanar approach and a good tissue differentiation characterize magnetic
      resonance imaging which have a great role in exploring numerous musculo-skeletal
      lesions; review of main indications and limits. MRI is useful in diagnosing
      certain undisplaced fractures, fatigue and insufficiency fractures, and
      consequences. Fibrous cartilage and hyalin cartilage lesions, tears of tendons,
      ligaments and muscles are well appreciated. MRI is also very good for an early
      and correct diagnosis of avascular necrosis, spinal degenerative lesions, spinal
      consequences of rheumatoid arthritis and ankylosing spondylitis, and bone
      metastases. It is the technique of choice for local staging of bone and soft
      tissue sarcomas.

PMID- 8761743
TI  - [Magnetic resonance angiography].
AB  - Magnetic resonance angiography (MRA) is a non invasive method for studying the
      morphology and the hemodynamic of vessels. MRA is becoming well-established for
      aorta examination and has replaced aortography. MRA is very competitive in
      screening for renovascular hypertension, intracranial aneurysm, for evaluation of
      the carotid bifurcation and diagnosis of venous sinus thrombosis. In the future,
      clinical applications will include pulmonary and coronary arteries.

PMID- 8761744
TI  - [Magnetic resonance imaging in pediatrics].
AB  - In this study, the authors present the problems related to MRI in children,
      mainly sedation. Main indications of this method in children are reported as well
      as the role compared to other imaging modalities. MRI is now a routine tool. Well
      oriented use of MRI remains consistent with the health expenses control and
      allows improvement of health care and shortens the diagnostic delays.

PMID- 8761745
TI  - [Magnetic resonance imaging of the pelvis].
AB  - Magnetic resonance imaging (MRI) is particularly well suited to pelvic
      explorations. Normal uterine zonal anatomy and its variations within the
      menstrual cycle are well codified. MRI is the best preoperative imaging modality
      for the localization of fibroids. MRI allows a good approach to tissue
      characterization in benign ovarian tumors and a precise loco-regional assessment
      in malignant tumors. It could eventually replace the surgical second look after
      therapy. In prostate cancer, MRI is the most accurate imaging modality to assess
      capsular invasion.

PMID- 8761746
TI  - [Future path of magnetic resonance spectroscopy in clinical medicine].
AB  - The metabolic exploration of skeletal muscle and brain by magnetic resonance
      spectroscopy (MRS) provides the basis of the main clinical applications of in
      vivo MRS on humans. Also, high resolution MRS is used in vitro to identify and
      assay the metabolites contained in physiological fluids (blood, urine, CSF). In
      these applications, MRS has became and will keep developing as the investigative
      tool of choice to perform non-invasively "live biochemistry" experiments on
      organs and tissues.

PMID- 8761747
TI  - [Statural growth retardation. Diagnostic orientation].

PMID- 8761748
TI  - [Leukorrhea. Diagnostic orientation].

PMID- 8761749
TI  - [Manic-depressive disease. Diagnosis, development, treatment].

PMID- 8761750
TI  - [Acne. Etiology, physiopathology, diagnosis, treatment].

PMID- 8761751
TI  - [Shoulder injuries. Diagnostic orientation].

PMID- 8761752
TI  - [Cancer of the esophagus. Epidemiology, etiology, diagnosis].

PMID- 8761754
TI  - [Dermatology, esthetic medicine, cosmetology].

PMID- 8761755
TI  - [Is cosmetology medical?].

PMID- 8761756
TI  - [Bone marrow autograft in the treatment of cutaneous lymphoma].
AB  - INTRODUCTION: The prognosis of advanced stage or high grade cutaneous lymphomas
      is very poor in case of recurrence after conventional polychemotherapy. Recent
      studies have confirmed the importance of intensified treatment with autologous
      bone marrow transplantation in case of recurrence. We used this method in
      patients with a cutaneous lymphoma with poor prognosis. PATIENTS AND METHODS:
      Seven patients with a high-grade or disseminated cutaneous lymphoma were given an
      autologous bone marrow graft in case of recurrence after one or more
      polychemotherapy protocols. In 4 patients, treatment included total body
      irradiation and high-dose chemotherapy (cyclophosphamide/etoposide, or
      aracytine/melphalan) and in the 3 others chemotherapy alone (BEAM or BEAC) was
      used prior to transplantation. RESULTS: Two complete remissions of 46 and 34
      months duration after graft were achieved without complementary treatment. One
      patient had partial remission. Recurrence was observed in 2 patients 5 months
      after the graft and in 1 other 30 months later. Prolonged complete remission was
      observed in patients given total body irradiation and the early recurrences in
      those given chemotherapy alone. DISCUSSION: This pilot study demonstrates that
      patients with a poor prognosis cutaneous lymphoma can achieve prolonged complete
      remission by therapy intensification using autologous bone marrow transplantation
      after total body irradiation.

PMID- 8761757
TI  - [Oropharyngeal candidiasis resistant to fluconazole in patients infected by HIV].
AB  - PURPOSE: To study the susceptibility to fluconazole of Candida albicans strains
      in oral candidiasis of HIV positive patients. PATIENTS AND METHODS: Eleven HIV
      positive patients with confirmed oral candidiasis were included in a 4 to 10
      months prospective study. In addition, 23 HIV positive patients were evaluated in
      a restrospective study (14 with oral candidiasis and 9 control subjects). The
      MICs to fluconazole of C. albicans were characterized by genotyping
      (electrophoretic karyotype). RESULTS: Thirty patients were evaluable. Oral
      candidiasis was found in 21 patients; 7/21 patients (33,3 p. 100) developed
      resistant C. albicans strain (MIC > 32 mg/ml) after a mean fluconazole cumulative
      dose of 18 g. In this study, the electrophoretic karyotype confirmed the
      persistence of the same C. albicans strain in each patient. In addition increased
      colonization by C. krusei or C. glabrata was found in 6/21 patients (28.5 p.
      100). DISCUSSION: Our data demonstrate that prolonged treatment with fluconazole
      dose higher than 13 g induces the emergence of resistant C. albicans with
      persistence of the same C. albicans strain. Fluconazole has to be reserved to
      oral candidiasis after failure of a local treatment or to severe cases.

PMID- 8761758
TI  - [Human papillomavirus 6/11 in conjunctival papilloma].
AB  - INTRODUCTION: Human papilloma virus is highly prevalent, but rarely localized in
      the conjunctiva. CASE REPORT: A 19-year-old man with no past history of skin or
      mucosal disease consulted for tumefaction of the conjunctiva. Exeresis revealed a
      viral papilloma. In situ hybridization was positive for human papilloma virus
      6/11. DISCUSSION: Conjunctival lesions of human papilloma virus are often located
      in the caroncula as in our patient. The papillomatous aspect of the tumour may
      suggest squamous cell carcinoma (sometimes induced by human papillomavirus
      16/18). Contamination may be manual or occur at birth via the maternal genital
      mucosa. Treatment usually is based on wide exeresis with cryo-application
      although spontaneous regression is possible.

PMID- 8761759
TI  - [Diffuse normolipidemic plane xanthomatosis and monoclonal dysglobulinemia. A
      case with anti-lipoprotein activity of monoclonal immunoglobulin and
      hypocomplementemia].
AB  - INTRODUCTION: Diffuse normolipaemic plane xanthomatosis associated with
      monoclonal dysglobulinaemia has been recognized as a clinical entity for more
      than 30 years. Antilipoprotein activity has been reported in certain cases with
      monoclonal immunoglobulinaemia or hypocomplementaemia. CASE REPORT: A 64-year-old
      woman developed simultaneously diffuse normolipaemic plane xanthomatosis and
      monoclonal IgG kappa dysglobulinaemia. This paraprotein was initially associated
      with monoclonal gammapathy of undetermined signification (called "benign") before
      evolving into a myeloma. This aggravation was associated with an expansion of the
      skin lesions. Immunological exploration demonstrated the presence of IgG
      lipoprotein complexes in the plasma and hypocomplementaemia suggesting incomplete
      activation of the classical pathway (low CH50 and fraction C4). DISCUSSION:
      According to the literature, the most probable hypothesis for the pathogenesis of
      the xanthomatosis-dysglobulinaemia association is a specific interaction between
      the monoclonal immunoglobulin and lipoprotein metabolism. In normolipaemic forms,
      the immunoglobulin-lipoprotein complexes are recognized by "waste-receptors" and
      accumulate in the dermal macrophages while the mechanism of lipoprotein captation
      in the other types of cells remains normal, explaining the absence of
      hyperlipidaemia.

PMID- 8761760
TI  - [Vulvar lymphangiectasis 14 years after treatment for epidermoid carcinoma of the
      cervix. Treatment with cryosurgery].
AB  - INTRODUCTION: Lymphangiectasia are different from lymphangioma because they arise
      following damage to the deeper lymphatic vessels. No clinical or histological
      features are known to distinguish lymphangioma from lymphangiectasia. CASE
      REPORT: We report a case of vulvar lymphangiectasia occurring 14 years after
      therapy of squamous carcinoma of the cervix (surgery and post-operative
      radiotherapy). Our treatment was cryosurgery. DISCUSSION: We analysed the 12 case
      reports of vulvar lymphangiectasia in the literature, emphasizing misleading
      clinical aspect of the warty lesions and the risk of repeated infection
      justifying an appropriate treatment. We propose cryosurgery which provides real
      benefits with a minimal trauma.

PMID- 8761761
TI  - [Transient bullous epidermolysis of the newborn infant. A benign clinical form of
      dystrophic bullous epidermolysis or an autonomous entity?].
AB  - INTRODUCTION: Transient bullous dermolysis of the newborn is a bullous eruption
      limited to friction zones. It appears at birth and disappears during the first
      months of life. CASE REPORT: Immediately after delivery, an infant girl presented
      cutaneous bullae on areas of trauma which spontaneously regressed after a few
      weeks. The histology examination confirmed subepidermal involvement (the roof of
      the bullae took up the anticollagen IV antibody) and ultrastructure anomalies in
      the baseline membrane: intracellular vacuoles in the keratinocytes containing
      fibrillary material, disorganization of the anchoring fibers. DISCUSSION:
      Transient bullous dermolysis of the newborn is a rare (less than 15 cases
      reported in the literature) benign disease which regresses spontaneously,
      possibly an explanation of the small number of cases reported. The anomalies in
      the ultrastructure observed in the baseline membrane strongly suggest transient
      impairment in collagen VII maturation and excretion. These anomalies are not
      pathognomonic and can be observed in dystrophic bullous epidermolysis. Currently
      there is no specific genetic marker to established transient bullous dermolysis
      as unique entity.

PMID- 8761762
TI  - [Mycobacterium avium-intracellulare subcutaneous abscess after injections of
      interferon alpha in a patient treated for lymphoma].
AB  - INTRODUCTION: Cutaneous involvement with Mycobacterium avium-intracellulare is
      usually observed in disseminated disease but cutaneous infection alone without
      bacteraemia is uncommon. CASE REPORT: We report a case of Mycobacterium avium
      intracellulare subcutaneous abscess of the thigh in a 32-year-old woman with
      lymphoma. The lesion was treated with drainage, excision and chemotherapeutic
      agents. Inoculation was probably secondary to alpha interferon injections
      performed during one year. DISCUSSION: The review of the literature shows that
      isolated Mycobacterium avium-intracellulare skin infections are rare, probably
      induced by traumatic percutaneous inoculation, frequently in immunocompromised
      patients. The pro-infectious effect of interferon alpha is considered. Treatment
      is unsatisfactory and surgical excision is often necessary.

PMID- 8761763
TI  - [Granulosis rubra nasi and pheochromocytoma].
AB  - INTRODUCTION: Granulosis rubra nasi, a papular red lesion of the nose associated
      with hypersudation is an uncommon dermatosis usually seen in children. CASE
      REPORT: A noradrenalin secreting pheochromocytoma was found in 19-year-old girl
      with hyperhidrosis, granulosis rubra nasi and tachycardia. Surgical exeresis of
      the pheochromocytoma was followed by involution of the hyperhidrosis, regression
      of the nasal dermatosis and normalization of urinary catecholamines. DISCUSSION:
      The diagnosis of pheochromocytoma should be entertained in patients with
      hypersudation and tachycardia. Granulosis rubra nasi could be a complication of
      hyperhidrosis.

PMID- 8761764
TI  - [Plantar hidradenitis].
AB  - INTRODUCTION: Plantar hidradenitis, one of several possible causes of painful
      papulo-nodular lesions of the foot in children and young adults, was recently
      described as the presence of characteristic lesions of the eccrine sweat glands.
      CASE REPORT: A 15-year-old boy consulted for a sudden-onset painful eruption on
      the sole of the right foot. Physical examination revealed papulo-nodular
      erythromato-violet infiltrated lesions located on the anterior part of the right
      planta. Histology examination showed dense neutrophil inflammatory infiltration
      predominating at the dermo-hypodermic junction around the eccrine sweat glands.
      The excretory ducts of the sweat glands were infiltrated but the secretory
      glomerulae were intact. A dense infiltration of venular thrombi without
      vasculitis was also seen. The lesion regressed with aspirin (8 days) and rest. No
      recurrence has been recorded after 18 months. DISCUSSION: This clinical and
      histological presentation led to the diagnosis of plantar hidradenitis,
      confirming the disease entity. Former cases may have been described as trauma
      induced plantar urticaria or plantar erythema nodosum. This diagnosis should be
      entertained in children or young adults with painful papulo-nodular eruptions of
      the soles. The histology examination should include the eccrine sweat glands.

PMID- 8761765
TI  - [White papulosis of the neck. Clinical aspects of pseudoxanthoma elasticum].
AB  - INTRODUCTION: Acquired elastolysis of the papillary dermis simulating
      pseudoxanthoma elasticum and white papulosis of the neck are two skin diseases
      with clearly limited borders. The two entities can be distinguished clinically
      when papulae converge into yellowish-white patches and histologically by complete
      absence of the elastic network in the papillary dermis without thickening of the
      collagen network in the superficial and mid dermis. CASE REPORT: We observed a
      patient with the clinical and histological criteria for acquired elastolysis of
      the papillary dermis. Histological examination showed a thick collagen network as
      described in white papulosis of the neck. DISCUSSION: This case clearly
      demonstrates the histological continuum between these two entities. A review of
      the literature also provided evidence of borderline forms, leading us to propose
      grouping them together. Elastolysis of the papillary dermis would appear to be a
      relatively specific histological sign differentiating white papulosis of the
      neck, in a general sense, and acquired elastosis of the mid dermis. Two factors
      could explain the rare observations of acquired elastosis of the mid dermis in
      patients with acquired elastosis of the papillary derma: use of the Verhoeff Van
      Gieson stain without an internal control and imprecise localization of the
      biopsy.

PMID- 8761766
TI  - [Multifocal lupus vulgaris].
AB  - INTRODUCTION: Lupus vulgaris is a subset of cutaneous tuberculosis, classically
      considered as the resurgence of an endogenous focus. The most usual clinical
      picture is a unique, often facial, patch and the association with deep, visceral
      specific lesions is rarely reported. OBSERVATION: A 69-year-old woman was
      referred for evaluation of multiple patches of the trunk and the limbs, with a
      histological picture of non caseating tuberculoid granuloma. A previous medical
      history of tuberculous primary infection of the lungs prompted search for lupus
      vulgaris, confirmed by the culture of cutaneous lesions. Numerous visceral
      specific lesions were likely present, especially in the liver. DISCUSSION:
      Multiple lesions are rarely reported in lupus vulgaris and may be confusing
      especially with sarcoidosis when confronted with non-specific granulomatous
      histology. This is especially true when there is visceral involvement,
      infrequently described in lupus vulgaris (a liver lesion has not been previously
      reported). Culture of cutaneous samples is required in case of doubt.

PMID- 8761767
TI  - [Facial involvement in papulous, prurient and urticarial skin disease in
      pregnancy].

PMID- 8761768
TI  - [Apropos of chronic urticaria and autoimmune thyroid diseases].

PMID- 8761769
TI  - [A case for diagnosis: Osler subacute endocarditis].

PMID- 8761770
TI  - [A case for diagnosis: mucous manifestations of psoriasis].

PMID- 8761771
TI  - [Extracutaneous manifestations of neutrophilic dermatosis].

PMID- 8761773
TI  - [How far should treatment of severe alopecia areata be managed?].

PMID- 8761772
TI  - [Physiopathology of leg ulcer of venous origin].

PMID- 8761774
TI  - [Allergologic survey in 251 patients with moderate or severe dermatitis.
      Incidence and value of the detection of contact eczema, food allergy or
      sensitization to air-borne allergens].
AB  - INTRODUCTION: Because of the increased recruitment of uncontrolled atopic
      dermatitis (AD) necessitating chronic use of dermocorticosteroids, we developed a
      prospective allergologic survey in a serie of 251 patients presenting with
      moderate or severe AD. PATIENTS AND METHOD: 251 patients were refered for
      allergologic assessment and followup. The clinical severity was assessed by use
      of standardized scores. Patients were grouped by age: group 1 (70 children
      younger than 2 years), group 2 (93 children between 2 and 7 years), group 3 (23
      children between 7 and 15 years), group 4 (65 children over 15 years and adults).
      All the patients were systematically screened for contact dermatitis and IgE
      mediated sensitization (inhallant and food allergens) with blood tests for IgE,
      prior to evaluation of clinical relevance. RESULTS: Aero-allergen sensitization
      was demonstrated in 51 p. 100 of children and 89 p. 100 of adults. It was present
      earlier in severe AD with main clinical involvement for nose and throat and
      respiratory symptoms. Clinical responsibility for dermatitis was documented in
      only 6 p. 100 of AD. Food allergy was early incriminated as flare factors in most
      of severe AD (96 p. 100 of children and 81 p. 100 of adults) with major and
      persistant improvement under eviction diet. Main allergens were eggs (46 p. 100),
      pea-nuts (29 p. 100), shellfish (24 p. 100), milk (20 p. 100), flour (14 p. 100),
      fish (14 p. 100), soybeans (8.9 p. 100). Food allergy to yeasts (7.2 p. 100) was
      important in adults. Food allergy is the earliest allergy in the course of severe
      AD and the number of involved trophallergens increases in older patients. Patch
      tests were positive in 40 p. 100 of patients (i. e. 31 p. 100 of children and 66
      p. 100 of adults) with a greater incidence in moderate AD. Main allergens were
      metals (54 p. 100), fragrances (19 p. 100), balsam of Peru (10 p. 100), parabens
      (8 p. 100) and lanoline (4 p. 100). CONCLUSION: When AD is not efficiently
      controlled by dermocorticosteroids, allergologic screening and treatment of
      children and adults proves to be very interesting. Specific measures regarding
      food allergy and contact dermatitis reduce or vanish cutaneous flares. As for
      inhallant sensitizations, Dermatologists should be awared that they may play a
      role regarding assessment of sensitization and prevention of respiratory symptoms
      in moderate and severe AD since the risk of complications is important in both
      groups.

PMID- 8761776
TI  - [Mibelli porokeratosis in 2 brothers].
AB  - INTRODUCTION: Mibelli's porokeratosis is uncommon in black persons. We report two
      brothers who had two different clinical presentations. CASE REPORT: The brothers
      were seen at the ages of 16 and 19 years. Both had Mibelli's porokeratosis, one
      with a papulo-verruciform presentation located on the scrotum, the anus, the
      gluteal area and the back of the hand, and the other with a superficial
      disseminated eruption involving the face and the forearm. DISCUSSION: The
      incidence of Mibelli's porokeratosis in the black population at Cotonou is
      approximately 0.3 per 10.000. The presence of the disease in two uterine brothers
      confirms the monogenic and familial nature of Mibelli's porokeratosis. Dominant
      transmission cannot be easily demonstrated when the parents of the patients are
      phenotypically healthy.

PMID- 8761775
TI  - [Comparative study of the efficacy and tolerability of 0.1 and 0.03 p.100
      adapalene gel and 0.025 p.100 tretinoin gel in the treatment of acne].
AB  - INTRODUCTION: Adapalene is a new chemical entity with retinoid activity. PATIENTS
      AND METHODS: 0.1 p. 100 adapalene gel (Differine gel), 0.03 p. 100 adapalene gel
      and a commercially available 0.025 p. 100 tretinoin gel (Aberel gel) were
      compared in 89 male and female patients with acne. RESULTS: Inflammatory, non
      inflammatory, total lesion counts, and the global facial acne grade regularly
      decreased as a function of time in the three treatment groups. No statistically
      or clinicaly significant differences were observed for these parameters between
      0.1 p. 100 adapalene gel and 0.025 p. 100 tretinoin gel following a 12-week
      treatment. Conversely, both of these gels were significantly more effective than
      0.03 p. 100 adapalene gel with regards to inflammatory and total lesion counts,
      and the global facial acne grade. The differences of efficacy seen between both
      adapalene gels demonstrate a dose-dependent activity of the drug in the topical
      treatment of acne. The three products induced retinoid-like skin irritation with
      significant differences in intensity in favour of adapalene for erythema,
      dryness, scaling and burning after application and in favour of tretinoin for
      persistent burning. No treatment-related medical events were reported and
      adapalene plasma levels were lower than 0.15 ng/ml (limit of detection of the
      analytical method). CONCLUSIONS: The topical treatment of acne with adapalene
      gels was found to be safe and effective, with a dose-related response. The
      efficacy of 0.1 p. 100 adapalene gel and of 0.025 p. 100 tretinoin gel are not
      different but skin tolerance of 0.1 p. 100 adapalene gel is superior.

PMID- 8761778
TI  - [Cutaneous hypersensitivity at the site of injection of vitamin K1].
AB  - INTRODUCTION: Skin reactions after vitamin K injections are uncommon and only
      seen with vitamin K1 (phytomenadione). Possible association with liver disease is
      debated. The pathophysiological mechanism would be related to hypersensitivity to
      phytomenadione. CASE REPORT: Two new cases of hypersensitivity reactions at the
      point of vitamin K1 injection are reported. Neither of the patients had liver
      disease. DISCUSSION: Injectable vitamin K1 can cause skin reactions whatever the
      dose and mode of injection. Two clinical presentations have been described: an
      acute eczematous aspect and a late onset sclerous and atrophic form. The first
      cases of hypersensitivity to vitamin K were reported in patients with liver
      disease. Several recent publications did not find such an association. Our two
      observations would confirm this hypothesis. The pathophysiological mechanism of
      the acute form would involve type IV allergy to phytomenadione as suggested by
      the delay between sensitization and reactivation, the histology, the patch tests
      which are positive with phytomenadione and negative with the carrier and the
      presence of reaction at rechallenge. However, the lack of the necessary
      sensitization phase and abnormally slow regression of eczematous lesions are
      unusual and might be explained by a particularly active antigenic effect of the
      phytomenadione molecule possibly related to the phytyl moiety.

PMID- 8761777
TI  - [Bleomycin in Kaposi disease in a patient with heart transplantation].
AB  - INTRODUCTION: Kaposi's disease is increasingly frequent in transplant recipients.
      The therapeutic approach in heart transplantation is not fully established. CASE
      REPORT: A 61-year-old male transplant recipient (June 1992) presented Kaposi's
      disease on the legs. Immunosuppressive therapy was reduced, cyclosporin by 20 p.
      100, withdrawal of azathioprine and 40 p. 100 reduction in prednisone was
      insufficient to control the disease. Due to the extension of the lesions and the
      major functional handicap, bleomycin was given and led to complete regression of
      the lesions within 6 months. DISCUSSION: This case illustrates the difficult
      therapeutic situation encountered in heart transplant recipients. The situation
      may be life-threatening with organ rejection. The first step is to reduce
      immunosuppressive therapy. If this is insufficient or the Kaposi is particularly
      aggressive, bleomycin may be used. The efficacy of bleomycin observed in our case
      requires confirmation in multicenter studies.

PMID- 8761779
TI  - [Malignant keratoma].
AB  - INTRODUCTION: Birth of an Harlequin fetus in an African maternity ward is an
      exceptional event. There is no question as to the diagnosis, but no treatment is
      available. CASE REPORT: A female infant was delivered with typical lesions of
      malignant keratoma. Death occurred 20 hours after birth. DISCUSSION: In countries
      with adequate intensive care facilities (hydration, acitretine), such infants may
      occasionally survive with the risk of developing major lamellar ichthyosis which
      remains a handicap for the rest of life. In Burkina-Faso, such therapeutic
      facilities are lacking as are means of antenatal diagnosis. The ethical question
      as to whether or not to attempt survival measures is quite different under these
      conditions.

PMID- 8761780
TI  - [Subcutaneous phycomycosis successfully treated with itraconazole].
AB  - INTRODUCTION: We report a case of basidiobolomycosis (subcutaneous phycomycosis),
      an uncommon deep mycosis in the entomophtoromycosis group. CASE REPORT: A 12-year
      old girl presented a deep skin infiltration involving the back and buttocks.
      Histology reported filamentous formations without septa surrounded by Splendore
      Hoepple phenomenon, the characteristic aspect of entomophtoromycosis. Outcome was
      favorable after treatment with itraconazole. DISCUSSION: Basidiobolomycosis is a
      deep mycosis rarely observed in children. Most reported cases have occurred in
      the tropics. The clinical presentation can simulate deep scleroderma or a tumoral
      disease. Treatment is currently based on imidazole derivatives which are
      particularly effective.

PMID- 8761781
TI  - [Severe contact dermatitis caused by mephenesin].
AB  - INTRODUCTION: Mephenesin is a muscle relaxant, mostly applied locally in trauma.
      It is a component of Traumalgyl cream in association with phenylbutazone. Contact
      dermatitis due to mephenesin is exceptional. CASE REPORT: We report here a case
      of a woman who developed after application of Traumalgyl cream purpuric
      dermatitis, erythema multiforme-like and urticarial lesions. Patch-tests were
      strongly positive (+ + +) for both Traumalgyl cream and mephenesin and (+) for
      phenylbutazone. Improvement of the lesions was observed within 3 weeks.
      DISCUSSION: Physicians must be aware of the risk of severe contact dermatitis
      after application of products including mephenesin because of their widely
      prescription.

PMID- 8761782
TI  - [Elastosis perforans serpiginosa with vitamin A deficiency in a child with
      trisomy 21].
AB  - INTRODUCTION: Elastosis perforans serpiginosa frequently occurs in trisomy 21.
      Usually no cause is found. We report a case in which vitamin deficiency may have
      contributed to the development of skin lesions. CASE REPORT: A 11-year-old girl
      with trisomy 21 developed papulokeratosic eruptions with a linear serpiginous
      distribution, predominantly involving the lower limbs. On ultrastructure
      examination, numerous elastic fibers penetrated the epiderma and the baseline
      membrane had disappeared. The patient also had a totally patent atrioventricular
      canal with hypoplasia of the left ventricle and cardiac liver. Serum vitamin A
      level was low (0.56 mumol/l, normal > 1.55). Acitretine was prescribed at the
      dose of 0.5 mg/kg/day but had to be stopped 2 months later due to elevated liver
      enzyme levels despite a clear clinical improvement. DISCUSSION: This association
      between elastosis perforans serpiginosa and vitamin A deficiency, observed here
      in a child with trisomy 21, has never been reported by others. Vitamin A
      deficiency might aggravate the skin lesions. In our case, there was probably a
      relationship between the vitamin A deficiency and the cardiogenic liver disease.
      The keratoregulatory effect of vitamin A on elastic tissue is less well known.
      Treatment with retinoids provided clinical improvement but had to be stopped due
      to hepatotoxicity. Parenteral vitamin A would be an interesting alternative but
      the risk of side effects would theoretically be greater than with oral retinoids.

PMID- 8761783
TI  - [Fusarium onychomycosis].
AB  - INTRODUCTION: A 69-year-old man with an uneventful past history consulted for a
      proximal subungueal leukonychia and associated paronychia of the right greater
      toe. Macroscopic examination and culture lead to the diagnosis of Fusarium
      oxysporum. Local treatment with bifonazol and cyclopirox was effective.
      DISCUSSION: Fungal onychomycoses are uncommon and usually present as superficial
      leukonychia. The association of a proximal localization with paronychia would
      suggest possible Fusarium infection. Though no specific treatment protocol is
      well-established, this case emphasizes the importance of effective treatment
      since invasive fusariosis is described in immunosuppressed patients with ungueal
      localizations can be an important portal for infection.

PMID- 8761784
TI  - [Cutaneous metastases of melanoma localized on the cicatrix at the site of flap
      taking].
AB  - INTRODUCTION: We report one case of melanoma cutaneous metastases strictly
      localized on a skin graft donor site distant from the tumor site. CASE REPORT: A
      patient with a shoulder melanoma was treated by surgery. A split-thickness skin
      graft was taken from a thigh to cover the raw area. Six months later, nodular
      cutaneous metastases strictly localized on the skin graft donor site appeared.
      COMMENTS: Physiopathology of those lesions is unknown. Hyaluronic acid is
      increased in granulation tissue and could be chimiotactic for melanoma cells.

PMID- 8761785
TI  - [Contact eczema caused by calcipotriol].

PMID- 8761786
TI  - [Severe contact dermatitis caused by bufexamac with large flap desquamation].

PMID- 8761788
TI  - [Epidermoid cysts of the toes].

PMID- 8761787
TI  - [Porphyria cutanea tarda and hepatitis C virus infection. Clinical and
      virological study].
AB  - INTRODUCTION: The role of hepatitis C virus (HCV) infection in porphyria cutanea
      tarda (PCT) is probable since the global antibody prevalence among PCT patients
      is about 70 p. 100. The purpose of this study was to evaluate the virological
      characteristics in 12 patients with sporadic PCT and one with familial PCT.
      METHODS: Anti-HCV antibodies were detected by enzyme-linked immunosorbent assay
      and confirmed by recombinant immunoblot assay. Hepatitis B virus (HBV) and anti
      human immunodeficiency virus (HIV) markers were also determined. The polymerase
      chain reaction (PCR) was performed in order to detect: 1) both positive and minus
      HCV strands, 2) HCV RNA titer and 3) HCV RNA genotype. RESULTS: Seven of the 12
      patients with sporadic PCT were HCV positive and the patient with familial PCT
      was HCV negative. The age of onset of PCT was significantly lower in HCV positive
      patients than in HCV negative patients (p < 0.02). The HCV RNA was detected in
      all patients who had HCV antibodies, and the replicative intermediate of HCV was
      detected in 3 of them. The positive RNA titer ranged from 1/10 to 1/10(6). Four
      patients were infected by HCV genotype I, 2 by genotype II and 1 patient was
      coinfected by type I and type II. Three of the 7 HCV positive patients also had
      HBV antibodies, but HBV DNA was never detected. All patients were HIV negative.
      DISCUSSION: The HCV infection rate was high in this series (58 p. 100), and all
      HCV infected patients had HCV RNA, reflecting an active replication of the virus.
      The young age of onset of PCT suggests that HCV is a major triggering factor of
      PCT. Nevertheless, the clinical changes of PCT were not related to the
      virological findings, suggesting an indirect role of HCV.

PMID- 8761789
TI  - [Malignant fibrous histiocytoma].

PMID- 8761790
TI  - [Parvovirus B19 infection. Current status].

PMID- 8761791
TI  - [Cutaneous allergies and insulin therapy. Current aspects, management].

PMID- 8761793
TI  - [Pyomyositis in adults in central Tunisia. Apropos of 10 cases].
AB  - Ten adult patients treated for pyomyositis between 1988 and 1994 in Sousse's
      university hospital (Tunisia) were retrospectively reviewed. Due to the non
      specific symptoms, the diagnosis was often delayed (mean = 17 days) and other
      primary diagnoses were considered, mainly including synovitis. The muscles around
      hip and thigh were most commonly involved (ten patients), and Staphylococcus
      aureus was the most common pathogen (nine patients). Ultrasonography was very
      helpful in the accurate diagnosis of the infection. Incision, drainage, and
      antibiotic therapy eradicated the infection in all patients. No residual
      functional limitations and no residual symptoms were noted. Our study showed that
      pyomyositis is present in central Tunisia and not associated with HIV infection.
      Clinical features and prognosis are similar to those previously described in the
      literature.

PMID- 8761792
TI  - [Pulmonary manifestations of primary Gougerot-Sjogren syndrome. Apropos of 8
      cases in a series of 35 patients].
AB  - Clinical, roentgenologic, functional and broncho-alveolar lavage features of lung
      involvement in primary Sjogren's syndrome were assessed in a retrospective study
      of 35 cases. Diffuse interstitial patterns on chest radiography were present in
      six patients and alveolar patterns were suggestive of lymphoid interstitial
      pneumonitis or pseudolymphoma in two. Acute and febrile onset mimicked infectious
      pneumonitis in three patients when dyspnea was the most common clinical feature
      in others. Patients with primary Sjogren's syndrome and pulmonary disease were
      older (65 vs 56 years) (P = 0.025), have more frequently extra-glandular
      manifestations (P = 0.03), keratoconjunctivis sicca (P = 0.018) and biological
      perturbations (hypergammaglobulinemia (P = 0.03), antinuclear antibodies (P =
      0.01) than those without lung involvement. Low diffusion capacity was present in
      seven patients associated twice to small airways obstruction. Bronchoalveolar
      lavage revealed in all cases an increased total cells count (mean: 6.96
      10(5)/mm3) and a lymphocytic alveolitis (range: 11 to 66%; mean: 38%) associated
      with an elevated percentage of alveolar neutrophils in four patients. A low
      CD4/CD8 ratio was related to a pejorative issue. Treatment consisted in
      corticotherapy combined with oral cyclophosphamide in case of pseudolymphoma.

PMID- 8761794
TI  - [Immunologic diseases and hepatitis C virus].
AB  - Active chronic hepatitis may be associated with various immunologic diseases. In
      the Mediterranean area and to a lesser extent elsewhere, hepatitis C virus, has
      often been detected in patients affected by mixed cryoglobulinemia,
      membranoproliferative glomerulonephritis, polyarteritis nodosa autoimmune type 2b
      hepatitis, Hashimoto's disease, Sjogren's syndrome and lichen ruber planus. These
      findings should not be considered fortuitous due to the elevated prevalence of
      autoantibodies and immunologic abnormalities observed in hepatitis C patients
      compared with subjects presenting other liver diseases. The pathogenetic
      evaluation of the association between these immunologic diseases and chronic
      hepatitis C has led us to suggest that diverse virus C and host induced factors
      may play a fundamental role in determining these immunologic diseases.

PMID- 8761795
TI  - [Immunopathological mechanisms of human immunodeficiency virus infection].
AB  - Human immunodeficiency virus (HIV) infection usually elicits an early, strong and
      efficient immune response, despite which the virus can persist in the organism by
      using a complex strategy. It escapes immune surveillance through direct and
      indirect effects on cells of the immune system; by modifying its biological
      properties; and by antigenic drift as a result of the immune response selective
      pressure. The immune response to the virus could also lead to detrimental
      immunopathological mechanisms. In particular, any immune stimulation may increase
      the viral load, and specific immunisation may lead to enhancement of infection.
      However, reports that some "at risk" non HIV-infected individuals present markers
      of cell-mediated immunity to the virus, and occurrence of "long-term survivors"
      strongly suggests that the immune response to HIV may sometimes be protective.
      Understanding the immunological mechanisms involved in this infection is thus
      essential.

PMID- 8761796
TI  - [Association of polymyositis and rheumatoid arthritis. Apropos of a new case not
      related to drug ingestion].
AB  - Muscular manifestations are frequent during rheumatoid arthritis, mostly induced
      by drugs. In contrast with rheumatoid myositis whose existence has been debated,
      penicillamine induced polymyositis and dermatomyositis are well described. We
      report a case of rheumatoid arthritis associated with non-drug induced
      polymyositis.

PMID- 8761797
TI  - [Monoclonal gammopathy and primary hyperparathyroidism. Apropos of 2 cases and
      review of the literature].
AB  - Frequency of primary hyperparathyroidism (HP) is increased in neoplasia. Though
      uncommon, both HP and monoclonal gammopathy are not exceptionally associated as
      seen in a literature review reporting 24 observations. The mechanism of this
      association remains unclear but does not seems coincidental. Association of
      hypercalcemia with gammopathy does not suggest systematically malignant
      hypercalcemia and implies the search for hyperparathyroidism. The authors report
      two patients presenting respectively a multiple IgD myeloma and an monoclonal
      gammopathy of undetermined signification associated with a parathyroid adenoma.

PMID- 8761798
TI  - [Arteriovenous fistula with cardiac insufficiency disclosing kidney cancer].
AB  - A 66 year-old woman free of any coronary and valvular heart disease presented to
      our hospital with acute and severe congestive heart failure associated with
      increased blood flow-angiography showed an intraparenchymatous arteriovenous
      fistula of the left kidney and a kidney cancer. The patient was discharged after
      nephrectomy and complete heart recovery as assessed from the normality of the
      hemodynamic exploration of the right ventricle.

PMID- 8761799
TI  - [Use of methotrexate in spondylarthropathies. Review of the literature].
AB  - Methotrexate (MTX) is one of the most effective treatments of rheumatoid
      arthritis. It has also been used in other conditions such as spondylarthropathies
      (SPA). The literature concerning MTX in SPA was reviewed. Thus, MTX has been
      mainly prescribed in psoriatic arthritis and Reiter's syndrome with success for
      dermatological manifestations of these diseases. However, only a few controlled
      trials have been conducted in psoriatic arthritis and only one placebo controlled
      study did not demonstrate a real beneficial effect. Furthermore, it seems that
      MTX has no influence on the radiological outcome of psoriatic arthritis. There
      has been no controlled study upon the efficacy of MTX in Reiter's syndrome,
      ankylosing spondylitis or arthropathy associated with inflammatory bowel
      diseases. Such studies in SPA are required to evaluate the responding conditions,
      the efficacy, the side-effects, and the effective dose of MTX.

PMID- 8761800
TI  - [Sapho syndrome].

PMID- 8761801
TI  - [Association of polymyositis, myasthenia gravis and thymoma].

PMID- 8761802
TI  - [Spontaneous hematoma of the spleen in primary cytomegalovirus infection in an
      immunocompetent patient].

PMID- 8761803
TI  - [Pure pulmonary form of Wegener disease].

PMID- 8761804
TI  - [Aluminum osteopathy in a patient hemodialysed for chronic renal insufficiency
      and treated by long term administration of sucralfate].

PMID- 8761805
TI  - [Hyperaldosteronism suppressible with glucocorticoids].

PMID- 8761807
TI  - Restenosis: pathophysiology and preventive strategies.

PMID- 8761806
TI  - Catheter-delivered ultrasound potentiates in vitro thrombolysis.
AB  - PURPOSE: To develop a catheter-directed method to enhance urokinase- mediated
      thrombolysis with use of ultrasound. MATERIALS AND METHODS: A prototype catheter
      was constructed by using a 9-F piezoelectric crystal capable of producing 640-kHz
      pulsed ultrasound energy. Clots formed in vitro from whole blood were trace
      labeled with iodine-125 fibrinogen, and the release of radiolabeled fibrin
      degradation products was measured in the presence of urokinase, ultrasound, or a
      combination of urokinase and ultrasound. RESULTS: By 30 minutes, clot lysis was
      more complete with urokinase plus ultrasound (78.7% +/- 5.3 [mean +/- SD]) than
      with ultrasound alone (19.3% +/- 10.0) or urokinase alone (47.9% +/- 10.0) (P <
      .001 for ultrasound and urokinase vs either alone). The time to 50% clot lysis
      was shortened by 46% on average with the application of urokinase and ultrasound
      compared with urokinase alone (P < .03). CONCLUSIONS: Catheter-based ultrasound
      enhances enzymatic thrombolysis in vitro and may be a practical means to reduce
      the dose of enzyme and the time needed to achieve clot lysis in vivo.

PMID- 8761808
TI  - Cragg covered stents in hemodialysis access: initial and midterm results.
AB  - PURPOSE: To report midterm follow-up after implantation of covered stents for
      hemodialysis access. PATIENTS AND METHODS: Over a 2-year period, a Cragg Endopro
      stent was placed in 14 patients (mean age, 66.6 years +/- 15) to treat
      angioplasty-induced ruptures (n = 3), pseudoaneurysm (n = 1), postangioplasty
      residual stenosis (n = 2), and early restenosis (n = 8, four of them in a
      Wallstent). RESULTS: Initial placement was successful in all cases. A clinical
      inflammatory reaction was observed in all three cases of placement in the
      forearm. When the covered stent was placed in a stenotic vessel, restenosis
      always occurred within 6 months. Primary and secondary patencies were 28.5% +/-
      13.9 and 67.8% +/- 14.5, respectively, at 6 months. Covered stents were of
      undoubtable benefit in one case of rupture after Wallstent failure and in one
      case of restenosis in a Wallstent. CONCLUSION: Covered Cragg stents are effective
      in controlling angioplasty- induced rupture and sometimes for maintaining patency
      after restenosis in a Wallstent. They do not prevent restenosis and are
      responsible for an inflammatory reaction of unknown origin and long-term effect.

PMID- 8761809
TI  - Stent placement in the renal artery: three-year experience with the Palmaz stent.
AB  - PURPOSE: To evaluate the long-term results of stent placement in the renal
      arteries. PATIENTS AND METHODS: From January 1990 to August 1994, 59 hypertensive
      patients underwent 64 stent placement procedures. Indications were residual
      stenosis after percutaneous transluminal renal angioplasty in 42 patients,
      restenosis in 20 patients, and acute dissection in two patients. Follow-up (mean,
      14 months) was obtained in 54 patients. Six-month restenosis rates were based on
      results of arteriography, and even more long-term patency rates were based on
      duplex ultrasound. RESULTS: Technical success was achieved in all patients. Major
      complications occurred in two patients. No minor or puncture-site complications
      were observed. The overall 6-month restenosis rate was 1.6% (2.9% for ostial
      lesions). Survival analysis with the Kaplan-Meier method showed primary and
      secondary patency rates of 92% +/- 3.6 and 98% +/- 1.9, respectively, at 1 year
      and 79% +/- 8.8 and 92% +/- 6.1, respectively, at 2 years. Seventy-six percent of
      hypertensive patients benefited from the procedure. However, renal function was
      not improved by stent placement. CONCLUSION: Stent placement in renal arteries is
      a useful adjunct to percutaneous transluminal angioplasty for atherosclerotic
      renal-artery stenoses.

PMID- 8761810
TI  - Percutaneous transluminal stent placement to treat subclavian steal syndrome.
AB  - PURPOSE: To describe nonsurgical stent placement to treat subclavian steal
      syndrome after failure of traditional balloon angioplasty. PATIENTS AND METHODS:
      Seven patients with subclavian steal syndrome underwent diagnostic angiography,
      which showed four stenoses and three occlusions of the proximal left subclavian
      artery. Most patients presented with vertigo, left arm claudication, or syncope.
      Initial balloon angioplasty failed; there was elastic recoil with more than 30%
      residual stenosis or subintimal dissection. The three occlusions were treated
      with urokinase pulse-spray thrombolysis. All seven patients then underwent stent
      placement. RESULTS: Initial technical success was achieved in all seven cases
      (100%), with an average right versus left arm blood pressure gradient of 0 mm Hg
      (-11 to 12 mm Hg) at mean follow-up of 12 months (4-24 months) (positive gradient
      = systolic pressure of right arm > that of left arm; negative gradient = systolic
      pressure of left arm > that of right arm). Symptoms of arm claudication and
      syncope resolved, and vertigo improved or resolved after the procedure. There
      were no deaths, strokes, or emboli in the perioperative or follow-up period.
      CONCLUSION: Percutaneous transluminal stent placement may be an effective
      treatment of subclavian steal syndrome in patients with lesions that are
      refractory to traditional angioplasty.

PMID- 8761811
TI  - Endovascular stent-graft exclusion of an aortobronchial fistula.

PMID- 8761813
TI  - Removal of a fractured retention wire of an Accufix "J" pacemaker lead with an
      Amplatz goose neck snare.

PMID- 8761812
TI  - Luminal changes in downsteam arteries after percutaneous interventions in iliac
      arteries: implications for balloon or stent size determination.
AB  - PURPOSE: To evaluate changes in the diameter of downstream iliac arteries after
      percutaneous interventions, which may be important for stent or balloon size
      determination. PATIENTS AND METHODS: Angiographic studies were reviewed
      respectively for 31 patients in whom a unilateral common iliac artery occlusion
      (n = 10) or a high-grade stenosis (> 75%; n = 21) was treated with stent
      implantation (26 patients) or balloon angioplasty (five patients). RESULTS:
      Before intervention, the ipsilateral downstream arteries showed a luminal
      reduction in 26 of 31 patients (mean 24% +/- 11.0; range, 6%-64%) compared with
      the opposite artery. This side-to-side difference was statistically significant
      for the external iliac artery (P = .000007) and for the common iliac artery
      distal to the obstruction (P = .017). In 17 of 26 patients, the side-to-side
      difference of the downstream external iliac artery was fully reversible
      immediately after intervention. In five patients, a luminal widening was noted.
      No change was seen in only four patients. CONCLUSION: Because downstream arteries
      often show a marked luminal widening after intervention, determination of balloon
      or stent size cannot be based solely on the diameter of downstream ("normal")
      ipsilateral artery before intervention.

PMID- 8761814
TI  - Percutaneous removal of a fully expanded Wallstent from the right ventricle with
      transesophageal echocardiography guidance.

PMID- 8761816
TI  - Vascular graft puncture.

PMID- 8761815
TI  - Testicular venographic demonstration of transverse testicular ectopia.

PMID- 8761817
TI  - Upper extremity deep venous thrombosis.

PMID- 8761818
TI  - Rule of 110.

PMID- 8761819
TI  - A method to evaluate the elastic behavior of vascular stents.
AB  - PURPOSE: To develop a simple method for determining the elastic behavior of
      vascular stents. MATERIALS AND METHODS: An experimental apparatus was constructed
      to determine the elastic behavior of four different vascular stents. Each stent
      was expanded within an artificial compliant vessel and was subjected to an
      increasing external pressure. The cross-sectional area of each stent was recorded
      at incremental changes in pressure. Compliance was estimated from the slope of a
      linear regression analysis fit to the pressure-area data in the elastic range of
      deformation. RESULTS: The self-expandable stents were the most compliant, and
      balloon-expandable stents exhibited the least compliance. The balloon- expandable
      stents initially deformed in an elastic manner and then yielded irrecoverably at
      higher pressures. CONCLUSION: A simple method has been devised that allows the
      elastic behavior of stents to be assessed. Quantification of stent compliance
      with this method is important as a predictor of stent resistance to compression
      in vivo.

PMID- 8761820
TI  - Effects of vascular stent surface area and hemodynamics on intimal thickening.
AB  - PURPOSE: To compare the in vivo response to a new mechanically expandable
      vascular stent with the response to an existing type of balloon-expandable stent.
      MATERIALS AND METHODS: Prototype stents were deployed by means of a balloon
      catheter in the left iliac arteries of four healthy dogs. Palmaz stents were
      deployed in the contralateral iliac arteries to act as a control, and all stents
      were explanted after 6 weeks. Arteriography was performed at the time of
      insertion and before harvest, and pressure gradients were measured across each
      stent. The stents were then harvested and submitted for histologic examination.
      RESULTS: The performance of the prototype stent was similar to that of the Palmaz
      stent with respect to structural integrity, migration, maintenance of
      intraluminal diameter, ease of deployment, radiopacity, and pressure gradients.
      Unlike the Palmaz stent, the prototype stent did not foreshorten during
      expansion. The stents showed a lack of uniformity in terms of the measured
      luminal area and neointimal accumulation. Neointimal accumulation was more
      confined to the struts of the prototype stent; the lumen therefore had a fluted
      appearance. Neointimal accumulation was more broadly distributed around the
      circumference of the vessel wall of the Palmaz stent. CONCLUSION: In vivo
      performance of the prototype stent was similar to that of the Palmaz stent. Stent
      geometry may be an important determinant of neointimal response and resultant
      long-term patency.

PMID- 8761821
TI  - Induced thrombosis in the pig inferior vena cava: a model of deep venous
      thrombosis.
AB  - PURPOSE: To establish a new animal model of deep venous thrombosis. MATERIALS AND
      METHODS: Fifteen young pigs underwent temporary interruption of the inferior vena
      cava (IVC) below the entry of the right renal vein by means of either a silicone
      band (surgical technique, n = 6) or an intraluminal balloon catheter
      (endovascular technique, n = 9), followed by injection of absolute ethanol.
      Lumbar veins within 3 cm below the obstruction were ligated or occluded
      interventionally. The iatrogenic caval obstruction was relieved after 2 days.
      RESULTS: Procedure-related mortality was 33% (n = 2) and 11% (n = 1) for the
      surgical and endovascular groups, respectively. An adherent, occlusive thrombus
      was found in all four of the remaining surgically treated animals and in six of
      eight animals treated percutaneously. The IVC remained patent in two animals in
      whom balloon migration occurred. Severe caval stenosis invariably occurred after
      surgical banding. CONCLUSION: IVC thrombi suitable for the study of various
      recanalization therapies can be reliably created with this pig model.

PMID- 8761822
TI  - Factors influencing the activation of platelets by nonionic contrast medium.
AB  - PURPOSE: To determine why nonionic, low-osmolality contrast media (LOCM) at high
      concentrations (> 30%) induce almost immediate platelet activation and to explore
      preventive measures. MATERIALS AND METHODS: Nonionic LOCM, when added to blood,
      activates platelets, raises the osmolality, and lowers the ionic strength. To
      clarify the mechanisms involved, platelet activation was studied in sodium
      chloride-sucrose solutions of varying osmolalities and varying ionic strengths.
      Several salts and Iloprost were evaluated as potential inhibitors of platelet
      activation. RESULTS: Platelets are activated by both osmolality and ionic
      strength changes. The salts most inhibitory to platelet activation were magnesium
      sulfate and sodium citrate. Iloprost lowered platelet activation to control
      levels at 4.3 ng/mL of nonionic LOCM and completely eliminated it at 8.6 ng/mL.
      CONCLUSION: Three-quarters of nonionic LOCM-induced platelet activation appeared
      to be due to increased osmolality-the remainder to the decrease in ionic
      strength. Magnesium sulfate and Iloprost are potent inhibitors of this type of
      platelet activation.

PMID- 8761823
TI  - Targeting of different ethiodized oil-doxorubicin mixtures to hypovascular
      hepatic metastases with intraarterial and intraportal injections.
AB  - PURPOSE: The distribution of different ethiodized oil-doxorubicin mixtures within
      and around hypovascular liver metastases in athymic nude mice was compared
      following either intraarterial or intraportal injections. MATERIALS AND METHODS:
      Six different mixtures of doxorubicin and ethiodized oil in water-soluble
      contrast material, shaken for 5, 10, 15, and 30 minutes, respectively, were
      prepared and the size of the oil droplets in the mixtures evaluated.
      Intraarterial and intraportal injections of mixtures shaken for 10 and 15 minutes
      were performed in mice bearing hypovascular hepatic colorectal metastases. In
      vivo video microscopy was used to evaluate microvascular flow and the
      biodistribution and the size of the oil droplets within and around the tumors.
      RESULTS: Oil droplets smaller than 20 microns in diameter were taken up by tumor
      nodules. There was no significant difference in oil droplet accumulation within
      the tumor between intraarterial and intraportal injections. Oil droplets larger
      than 20 microns occluded small and medium portal branches. The optimum
      combination was 0.1 mL of ethiodized oil in 2 mL of diatrizoate sodium meglumine
      (Renografin-76) shaken for 15 minutes at 800 rpm, which formed droplets smaller
      than 20 microns (92%). CONCLUSION: Avascular regions of hepatic metastases may be
      embolized with ethiodized oil-anticancer drug mixtures containing oil droplets
      smaller than 20 microns. Since these droplets penetrate to the tumor interstitium
      with either intraarterial or intraportal injections, chemoembolization via the
      arterial route seems preferable for treatment of unresectable hypovascular
      hepatic metastases since it is easier to perform. The conclusions drawn from this
      study are limited to the animal model for experimental hypovascular hepatic
      metastases.

PMID- 8761824
TI  - Transcatheter arterial chemoembolization in inoperable hepatocellular carcinoma:
      four-year follow-up.
AB  - PURPOSE: To evaluate the efficacy of repeated chemoembolization in patients with
      inoperable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: One hundred
      thirty-two patients with HCC underwent transcatheter arterial chemoembolization
      with an emulsion of iodized oil and cisplatin. In 104 patients, "light" gelatin
      sponge embolization was also used. Chemoembolization was repeated every 1.5-3.0
      months in most patients (range, one to 18 chemoembolization sessions). RESULTS:
      In 74 patients, the HCCs became smaller or disappeared after chemoembolization.
      Decreases in size were seen in 55 of 76 HCCs 9 cm or smaller, 17 of 42 HCCs
      between 9 and 18 cm, and two of 14 HCCs larger than 18 cm. Use of gelatin sponge
      pledgets enhanced the response in tumors larger than 9 cm. Seven of 74 HCCs that
      responded to chemoembolization increased in size later. New daughter nodules that
      appeared at other sites responded to chemoembolization in 24 of 40 patients.
      Further new nodules appeared in 14 of 24 patients, and in six patients they
      responded to therapy. Median survival was 26 months for patients with responsive
      HCCs and 5 months for those with unresponsive lesions. CONCLUSION: Tumor size at
      the start of chemoembolization influenced the response to treatment and survival.
      The addition of gelatin sponge improved results only in tumors larger than 9 cm.
      Recurrence after an initial response was due more to the appearance of new
      daughter nodules in new locations rather than recrudescence of the presenting
      tumor.

PMID- 8761825
TI  - Percutaneous ureteral stents: a modified system to facilitate antegrade
      placement.

PMID- 8761826
TI  - US-guided percutaneous gastrostomy: a portable technique.

PMID- 8761827
TI  - Percutaneous transhepatic embolization of bile duct fistulas.

PMID- 8761828
TI  - Venography in the lordotic projection to facilitate central venous access.

PMID- 8761830
TI  - Comparative in vitro study of two percutaneous hydrodynamic thrombectomy systems.
AB  - PURPOSE: To test the efficacy of clot removal in small- and large-caliber vessels
      and determine the extent of procedure-related particle embolization for two
      rheolytic thrombectomy devices, the Hydrolyser and Angiojet. MATERIALS AND
      METHODS: Both systems were applied with and without guiding catheters in an
      arterial (7-mm tube diameter, wall-adherent thrombus [mean, 5.3 g], flow of 500
      mL/min)and a venous (20-mm tube diameter, free-floating thrombus [mean, 12 g],
      flow of 1,500 mL/min) flow model. RESULTS: Particle embolization was
      significantly lower for the Angiojet device (mean, 1.8% +/- 2.9 [standard
      deviation] vs mean 4.8% +/- 6.1 for particles > 1,000 microns). When the devices
      were used without guiding catheters, mean clot removal rates were 65% +/- 12 with
      the Hydrolyser and 49% +/- 9.2 with the Angiojet in the arterial flow model and
      88% +/- 15.5 with the Hydrolyser and 85% +/- 17.8 with the Angiojet in the venous
      flow model. Significant improvements in clot removal rates were achieved with use
      of guiding catheters: 81% +/- 5.4 with the Hydrolyser and 89% +/- 3.9 with the
      Angiojet in the arterial flow model and 95% +/- 1.4 with the Hydrolyser and 97%
      +/- 0.84 with the Angiojet in the venous flow model. CONCLUSION: Use of guiding
      catheters improved the performance of both systems significantly. Both rheolytic
      catheters remove sufficient amounts of soft thrombus from a large-caliber vessel,
      especially when applied with a guiding catheter. However, firmer thrombus is
      difficult to remove. The particle embolization rate is low for both systems.

PMID- 8761829
TI  - Interventional techniques to shorten and lengthen central venous catheters to
      preserve function.

PMID- 8761831
TI  - Comparison of arterial wall reaction after passage of the Hydrolyser device
      versus a thrombectomy balloon in an animal model.
AB  - PURPOSE: This study was designed to compare the reaction of the vessel wall after
      application of the Hydrolyser hydrodynamic thrombectomy device to the reaction
      after use of a balloon thrombectomy catheter. The influence of the vessel inner
      diameter on vessel wall reaction was evaluated after passage of the Hydrolyser.
      MATERIALS AND METHODS: After measurement of the vessel inner diameter with
      intravascular ultrasound (US), 102 segments of femoral and carotid arteries of
      goats were treated with one of the following four procedures: passage of the
      intravascular US catheter alone; passage of the Hydrolyser without or with an
      activated jet; or passage of an inflated thrombectomy balloon. Histologic
      evaluation was performed after 3 weeks. RESULTS: Intimal thickening (more than
      five cell layers of neointima) 3 weeks after treatment occurred more frequently
      after passage of the balloon than after any of the other procedures (P < .001).
      For vessels with a diameter of 3-4 mm, 4-5mm, or more than 5 mm, no significant
      difference in vessel wall reaction was observed following Hydrolyser passage.
      CONCLUSION: In this model, passage of the Hydrolyser device resulted in less
      intimal reaction compared with the thrombectomy balloon.

PMID- 8761832
TI  - Treatment of biliary strictures with metallic stents in liver transplant
      recipients.

PMID- 8761833
TI  - Retrieval of a titanium Greenfield filter delivered into the introducer sheath.

PMID- 8761834
TI  - How cardiac rehabilitation is being influenced by changes in health-care
      delivery.

PMID- 8761835
TI  - Selecting training workloads using treadmill test heart rate/oxygen uptake
      regressions.

PMID- 8761836
TI  - Women's and men's preferences for cardiac rehabilitation program features.
AB  - BACKGROUND: Current theories of human health behaviors suggest that clients'
      preferences for specific aspects of a health regimen are an important influence
      on their decisions to initiate and continue use of the regimen. Despite low rates
      of participation in cardiac rehabilitation programs, especially among women,
      little research has been done to determine patient preferences for features of
      cardiac rehabilitation programs. The purpose of this study was to identify and
      compare women's and men's preferences for specific cardiac rehabilitation program
      features. METHODS: Using a descriptive survey design, a convenience sample of 65
      individuals (33 men and 32 women) participating in a cardiac rehabilitation
      program completed a self-administered survey in which they indicated both the
      importance of each of 17 cardiac rehabilitation program features and the extent
      to which they had experienced each of the features. RESULTS: Convenience factors
      (drive time, transportation, noninterference with other life activities, and ease
      of learning the exercises) were well-met preferences for both women and men.
      Men's and women's preferences were not well met for being able to discuss their
      progress with professionals and the ability to choose their own exercises. Men
      indicated that the ability to set their own goals was their greatest unmet
      preference. Women's preferences for not having pain and not tiring while
      exercising were significantly less well met than those of men. CONCLUSIONS: These
      findings suggest that a cardiac rehabilitation program that is responsive to
      client preferences should emphasize joint goal setting with participants and
      discussion of progress, offer frequent encouragement from professionals, and
      provide a range of exercise choices. Attention to women's concerns about pain and
      fatigue while exercising should also be addressed in the program.

PMID- 8761837
TI  - Relationship between increased peak oxygen uptake and modifications in skeletal
      muscle metabolism following rehabilitation after myocardial infarction.
AB  - PURPOSE: Rehabilitation after myocardial infarction produces an increased peak
      oxygen uptake (VO2peak). This study investigates the relationship between the
      modifications in skeletal muscle metabolism and the modification in VO2peak
      induced by a standard program of physical training following a myocardial
      infarction. METHODS: Seventeen patients (14 male, 3 female) were studied by
      phosphorus 31(31P) magnetic resonance spectroscopy after the acute phase of a
      myocardial infarction and after 2 months of rehabilitation. Changes in calf
      muscle pH, phosphocreatine, and inorganic phosphates were measured at rest and
      during a plantar flexion-type incremental workload protocol. Calf muscle pH,
      phosphocreatine/(phosphocreatine + inorganic phosphates), and inorganic
      phosphates/phosphocreatine ratios were compared at the highest identical workload
      attained in both studies. The VO2peak (mL/kg/min) was determined during a cycle
      stress test. RESULTS: At the highest identical workload attained in both tests,
      the ratio phosphocreatine/(phosphocreatine + inorganic phosphates) was
      significantly higher (0.48 +/- 0.15 to 0.57 +/- 0.18: P < .001), and the ratio
      inorganic phosphates/phosphocreatine was lower (1.38 +/- 1.14 to 0.99 +/- 0.87: P
      < .01). After rehabilitation, no difference was observed for the pH at stress
      (6.83 +/- 0.16 to 6.91 +/- 0.14: not significant [NS]). The increase in the
      VO2peak was significant after rehabilitation (24 +/- 9 to 29 +/- 11 mL/kg/min: P
      < .001). The VO2peak improvement induced by the physical training was correlated
      with the increase in the phosphocreatine/(phosphocreatine + inorganic phosphates)
      (r = 0.818, P < .001). CONCLUSIONS: The reduction in phosphocreatine depletion
      indicated that the oxidative capacity of the skeletal muscle was improved during
      the rehabilitation. The good correlation between the indexes of skeletal muscle
      metabolism and VO2peak suggests the peripheral effect of training.

PMID- 8761838
TI  - Tri-state region pulmonary rehabilitation survey. Delivery of exercise
      conditioning services. The Pulmonary Rehabilitation Committee, Tri-State Society
      for Cardiovascular and Pulmonary Rehabilitation.
AB  - PURPOSE: This report analyzes the delivery of exercise conditioning services in
      the 1991 Pennsylvania, New Jersey, and Delaware regional survey of pulmonary
      rehabilitation programs. METHODS: Data from a questionnaire was analyzed with
      special consideration given to whether the program provided services for patients
      with only pulmonary diseases (n = 41) or with cardiac and pulmonary diseases (n =
      18). RESULTS: All 59 programs included exercise conditioning. Most programs (67%)
      used oxygen saturation and/or expired gas analysis for writing exercise
      prescriptions. Only pulmonary programs used 6- or 12-minute walk data. The
      exercise prescription was written by nonphysicians in 51% of the programs. Most
      pulmonary-only programs used respiratory therapists by themselves or in
      combination with other professionals as exercise supervisors (71%).
      Cardiopulmonary programs used exercise physiologists by themselves (22%) or
      nurses by themselves or in combination with other professionals (50%). For all
      programs, the standard for ratio of patients to exercise staff averaged 3.0:1.
      Pulmonary-only programs did slightly but significantly more continuous arterial
      oxygen percent saturation (SaO2) monitoring rather than spot checking. A standard
      determining the use of supplemental oxygen during exercise was reported by 78% of
      all programs. Most used supplemental oxygen after observing the SaO2 level
      falling to < 90%. Electrocardiograph monitoring was done in 66% of pulmonary-only
      programs, but in 94% of the cardiopulmonary programs. Maintenance sessions were
      offered by 64% of the pulmonary-only programs and also by 78% of the
      cardiopulmonary programs. CONCLUSION: The type of rehabilitation program, either
      pulmonary-only or cardiopulmonary, appears to influence the exercise conditioning
      services used by the pulmonary patient.

PMID- 8761839
TI  - Effects of 2,000 kcal per week of walking and stair climbing on physical fitness
      and risk factors for coronary heart disease.
AB  - BACKGROUND: Epidemiologic evidence suggests that 8,368 kJ or 2000 kcal per week
      of moderate physical activity, including walking and stair climbing, can reduce
      risk of coronary heart disease (CHD). The goal of this study was to assess the
      effects of this amount of these two activities on physical fitness and risk
      factors for CHD. METHODS: Twenty-two healthy, slightly overweight, sedentary,
      normotensive, normolipemic men, age 22 to 44 years, were randomly assigned to an
      exercise or control group for 12 weeks followed by a 4-week washout period. The
      subjects then were crossed-over to the alternate group for an additional 12-week
      period. Exercise consisted of 5 days per week of supervised treadmill exercise
      plus stair climbing. Treadmill exercise consisted of walking for 45 minutes at
      5.15 km per hour at 2% grade for a total of 19.3 km per week. Subjects also
      climbed 10 floors of stairs at a time at their own pace without prescribed target
      heart rates for a total of 50 floors per week. The estimated total weekly energy
      cost of the treadmill walking plus stair climbing was 8,368 kJ or 2,000 kcal.
      Mean observed heart rates were 55% and 82% of maximal heart rate during treadmill
      walking and stair climbing, respectively. Data from the two exercise periods and
      two control periods were pooled and compared by analysis of variance. RESULTS:
      Sixteen subjects completed all phases of the study. Maximal oxygen uptake
      (VO2max) by the Bruce treadmill exercise protocol with metabolic gas measurements
      was below average for age at baseline, and was not significantly affected by 12
      weeks of training. No significant changes were noted between groups in body
      weight or percent body fat (hydrostatic weighing), although there was a trend for
      loss of weight and fat with exercise training. Mean systolic blood pressure (119
      mm Hg) was unchanged in both groups. However, diastolic blood pressure (72 mm Hg
      and 78 mm Hg for the treatment and control groups, respectively) showed an
      unexpected 6 mm Hg increase during the exercise period and a 5 mm Hg decline
      during the control period. Mean plasma lipid and lipoprotein levels were
      unaffected by training, except for a 16% reduction in triglycerides (P < .05).
      However, a 28% increase in plasma high density lipoprotein (HDL)-cholesterol (P <
      .01) was noted during the initial 12-week training period, which regressed during
      the washout period, and was not replicated during the second 12-week exercise
      period. CONCLUSIONS: Twelve weeks of walking and stair climbing at a moderate
      pace and intensity at an energy cost of about 2,000 kcal per week failed to
      improve physical fitness or risk factors for CHD. A reduction in physical
      activities other than the prescribed exercise program, as reported by a physical
      activity recall questionnaire, probably contributed to an absence of an exercise
      response. A longer and/or a more intense activity program is apparently required
      to improve these modalities.

PMID- 8761840
TI  - Exercise training for patients with chronic atrial fibrillation.
AB  - BACKGROUND: Patients with atrial fibrillation (AF) referred for exercise
      rehabilitation exemplify the problem inherent in reliance on pulse rate to
      prescribe and monitor training intensity. METHODS: Exercise training was
      accomplished by specifying a training walking pace based on 60% to 80% of the
      peak oxygen intake (VO2max), as determined by the analysis of expired air
      (Horizon metabolic cart), and/or the ventilatory threshold (VT), together with a
      perceived exertion of 12 to 14 on the original Borg scale of perceived exertion.
      RESULTS: At the end of 1 year, a significant training effect was demonstrated
      (VO2max average increase 15%, 14.8 +/- 3.6 mL/kg/min to 17.0 +/- 3.6 mL/kg/min, P
      < .02; VO2 at VT, average increase 14%, 11.2 +/- 2.2 to 12.8 +/- 2.6 mL/kg/min, P
      < .01; peak power output increase 21%, 92.5 +/- 29.3 Watts to 112 +/- 3.7 Watts,
      P < .05) in a group of 20 patients (13 men, 7 women) with chronic atrial
      fibrillation. CONCLUSIONS: Patients with chronic atrial fibrillation can achieve
      significant functional gains from an exercise rehabilitation program.

PMID- 8761841
TI  - Intracellular free Ca2+ movements in cultured cardiac myocytes as shown by rapid
      scanning confocal microscopy.
AB  - Two-dimensional images of intracellular free Ca2+ movements in cultured cardiac
      myocytes were obtained at 33-ms intervals with a Ca(2+)-sensitive fluorescence
      probe, fluo-3, and a rapid scanning confocal laser microscope, a prototype of
      Nikon RCM8000. The cells used were isolated from the ventricular myocardium of
      neonatal mice, cultured for approximately 72 h and loaded with fluo-3. One type
      of cytoplasmic Ca2+ movement observed was a simultaneous increase in [Ca2+]
      throughout the cytoplasm, termed a "spike"; another type was a local increase in
      [Ca2+] propagating in the cytoplasm, termed a "wave." Cells with either spike or
      wave or both types of movements were observed. Tetrodotoxin (TTX) 10(-5) M,
      nicardipine 10(-6) M, and increased extracellular potassium concentration (40 mM)
      selectively inhibited spike, and ryanodine 10(-6) M and cyclopiazonic acid (CPA)
      3 x 10(-6) M selectively inhibited wave. These results indicate that spike was
      triggered by depolarization-induced Ca2+ influx across the sarcolemma, whereas
      wave was a propagating local increase in Ca2+ due to Ca2+ release from the
      sarcoplasmic reticulum (SR). On spike, nuclear [Ca2+] was shown to increase and
      decrease synchronously with cytoplasmic [Ca2+], with a delay and slower time
      course.

PMID- 8761842
TI  - Metabolic neutrality of perindopril: focus on insulin sensitivity in overweight
      patients with essential hypertension.
AB  - To assess the effects of antihypertensive treatment with the angiotensin
      converting enzyme (ACE) inhibitor perindopril on insulin sensitivity, plasma
      insulin, and lipoprotein metabolism in overweight hypertensive patients, we
      measured the insulin sensitivity index (SI, determined according to the minimal
      model method of Bergman), fasting plasma insulin and glucose concentrations,
      serum total triglyceride and lipoprotein cholesterol fractions, and blood
      pressure (BP) in 30 overweight [mean body mass index (BMI) 30.9 kg/m2],
      nondiabetic patients with essential hypertension after a 4-week run-in period and
      after 6 weeks of perindopril (n = 20) or placebo (n = 10) administered in a
      double-blind fashion. Furthermore, we estimated their state of physical fitness
      using the Conconi bicycle ergometer test before and after perindopril or placebo
      administration. SI was low in our study population (3.2 vs. 13.3 10(-4) ml.microU
      1.min-1 in normal lean control subjects). It did not differ between the
      perindopril and placebo group after the placebo run-in period (3.1 vs. 3.3 x 10(
      4) ml.microU-1.min-1) and was not influenced by perindopril (3.3 x 10(-4)
      ml.microU-1.min-1) or placebo (3.6 x 10(-4) ml.microU-1.min-1) treatment.
      Moreover, no significant changes were apparent in fasting plasma insulin and
      glucose, the areas under the glucose and insulin curves, the glucose
      disappearance rates, serum total triglycerides (TG), or cholesterol or
      lipoprotein cholesterol fractions between run-in and active treatment phases in
      the perindopril or the placebo group, respectively. Heart rate (HR), body weight,
      and anaerobic threshold remained stable in both groups. Compliance, assessed by
      pill counting was > 90% in both groups at all visits. Therefore, the ACE
      inhibitor perindopril is neutral with regard to insulin sensitivity, plasma
      insulin and glucose, and lipoprotein metabolism in overweight, nondiabetic
      patients with essential hypertension.

PMID- 8761843
TI  - Potent antifibrillatory effect of combined blockade of calcium channels and 5-HT2
      receptors with nexopamil during myocardial ischemia and reperfusion in dogs:
      comparison to diltiazem.
AB  - The need for novel antifibrillatory therapy is underscored by clinical trials
      indicating that the incidence of sudden cardiac death is increased by sodium or
      potassium channel blockade and is only partially reduced by beta-blockade. We
      examined the efficacy of nexopamil, which possesses the unique combination of
      calcium channel and 5-HT2 receptor blockade, in preventing ventricular
      tachycardia (VT) and fibrillation (VF) and reducing T-wave alternans magnitude
      during coronary artery occlusion and abrupt reperfusion in dogs. The results were
      compared with L-type calcium channel blockade alone with diltiazem. The effect of
      nexopamil was tested during a 10-min period of left anterior descending (LAD)
      coronary artery occlusion and release in chloralose-anesthetized dogs. T-wave
      alternans magnitude was assessed by complex demodulation. The drug reduced the
      incidence of VT during occlusion (from 5 of 6 to 0 of 6, p < 0.03) and VT/VF
      during abrupt reperfusion (from 5 of 6 to 0 of 6, p < 0.03) and suppressed the T
      wave alternans magnitude increase induced by occlusion (from 14.62 +/- 3.96 to
      1.39 +/- 0.34 mV x ms, p < 0.01) and reperfusion (from 17.33 +/- 4.67 to 2.34 +/-
      0.77 mV x ms, p < 0.01). When 30-s left stellate ganglion stimulation (10 V, 5-ms
      pulses, 10 Hz) was superimposed on occlusion, nexopamil reduced the VT/VF
      incidence (from 8 of 11 to 4 of 11, p < 0.05) and T-wave alternans magnitude
      (from 24.80 +/- 5.05 to 15.81 +/- 5.09 mV x ms, p < 0.05). Calcium channel
      blockade alone with diltiazem decreased the incidence of ventricular
      tachyarrhythmias (from 5 of 10 to 1 of 10, p < 0.05) and T-wave alternans
      magnitude (from 16.75 +/- 3.06 to 2.87 +/- 1.23 mV x ms, p < 0.05) during
      coronary artery occlusion. During reperfusion, diltiazem's reduction in
      arrhythmia incidence (from 5 of 8 to 2 of 8) was not statistically significant,
      although the decrease in T-wave alternans (from 28.60 +/- 3.43 to 8.27 +/- 3.73
      mV x ms, p < 0.05) was significant. Therefore, nexopamil was superior to
      diltiazem in protecting against reperfusion-induced arrhythmias. Nexopamil's
      significant antifibrillatory effect during both coronary artery occlusion and
      abrupt reperfusion is reliably tracked by T-wave alternans magnitude. Because the
      major component of the protection could be reproduced by blockade of the L-type
      calcium channel with diltiazem, nexopamil's antiarrhythmic action appears to be
      due mainly to blockade of this channel. Nexopamil's antiplatelet action through
      blockade of 5-HT2 receptors may confer additional protection against reperfusion
      arrhythmias.

PMID- 8761844
TI  - A dose-effect study of beraprost sodium in intermittent claudication.
AB  - We compared the efficacy and safety of three doses of beraprost sodium, an
      epoprostenol analogue, with placebo in the treatment of intermittent claudication
      (Fontaine's stage II). One hundred sixty-four patients were randomized to receive
      either placebo, 20 micrograms beraprost sodium (BPS60 group), 40 micrograms
      beraprost sodium (BPS120 group), or 60 micrograms beraprost sodium (BPS180 group)
      three times daily administered orally in a double-blind manner for 12 weeks.
      Treadmill exercise tests were performed twice during an initial selection phase
      (D-28 and D0) at week 10 (at trough beraprost concentration) and week 12 (at peak
      beraprost concentration) of the treatment phase. At week 10, all groups showed an
      increase in pain-free walking distance, and this distance was greatest in the
      BPS60 and BPS120 groups (p = 0.055). At week 12, a similar pattern was observed,
      and the difference was significant between the groups (p = 0.023). The most
      frequent adverse events reported were gastrointestinal disorders, headaches, skin
      disorders, and flushes. Patients who received either 60 or 120 micrograms of
      beraprost sodium daily had an increased pain-free walking distance. Further
      studies are required to investigate why the highest dose used (180 micrograms
      daily) showed lower efficacy. Having both vasodilating and antiplatelet
      properties and being able to increase pain-free walking distance in the short
      term, beraprost sodium is a promising drug for the treatment of intermittent
      claudication.

PMID- 8761845
TI  - Effect of methylisobutyl amiloride on [Na+]i, reperfusion arrhythmias, and
      function in ischemic rat hearts.
AB  - With 2 microM methylisobutyl amiloride (MIA), an inhibitor of Na+/H+ exchange, we
      tested the hypothesis that ion imbalance due to H+/Na+/Ca2+ exchange exacerbates
      reperfusion injury and arrhythmias. Isolated rat hearts were subjected to 25-min
      global ischemia and 30-min reperfusion. In the MIA-treated group, MIA was added
      throughout the perfusion protocol. Left ventricular pressure (LVP), arrhythmias,
      myocardial Na+ and K+ content, 45Ca2+ uptake, and the levels of energy
      metabolites were analyzed. The recovery of LV developed pressure (LVDP) and
      +dP/dt and -dP/dt were improved in the MIA group (53 vs. 80, 71 vs. 86, 77 vs.
      94%: each p < 0.05). MIA inhibited the increase in Na+ content and the decrease
      in K+ content that occurred at the end of the ischemic phase and reduced 45Ca2+
      uptake after reperfusion (28.6 vs. 17.1, 248 vs. 296, 2.79 vs. 1.36 microM/g dry
      weight of tissue; each p < 0.05). The incidence of ventricular tachycardia (VT)
      or ventricular fibrillation (VF) was lower in the MIA group [VT 11 of 20 (55%)
      vs. 4 of 20 (20%), p < 0.05; VF 13 of 20, (65%) vs. 6 of 20 (30%), 0.05 < p <
      0.1], although the incidence of VF just escaped statistical significance. ATP
      level was higher in the MIA group after the ischemic phase and reperfusion (5.3
      vs. 9.9, 12.3 vs. 14.7 microM/g dry weight of tissue; each p < 0.05). Our results
      suggest that MIA reduced reperfusion arrhythmias and improved functional recovery
      in isolated rat hearts subjected to global ischemia apparently by preserving high
      energy phosphates during ischemia and by inhibiting Na+/H+ exchange, with
      attenuated cellular imbalance between Na+ and Ca2+.

PMID- 8761846
TI  - Endothelial dysfunction in the San Juan hypertensive rat: possible role of the
      nitric oxide synthase.
AB  - Endothelial dysfunction is recognized as a critical event in the etiology of
      cardiovascular diseases, but its possible role during aging in arterial
      hypertension remains poorly defined. We evaluated the response of aortic rings
      precontracted with 0.1 microM norepinephrine (NE) to acetylcholine (ACh) in the
      San Juan hypertensive rats (SJH-Rs) (F19, F20) and Munich Wistar rats (MW). SJH
      Rs is a model of inbred salt-sensitive hypertension, whereas similarly treated
      inbred MW rats are their normotensive counterpart. These experiments were
      performed with adult (6-7 months) and aged (11-13 months) rats to assess the
      effects of age and hypertension on endothelium-dependent relaxation. We generated
      dose-response curves by adding cumulative doses of ACh from 1.0 nM to 10.0
      microM. In addition, we evaluated the Ca(2+)-dependent nitric oxide synthase
      (NOS) activity by increasing cell calcium with the ionophore A23187. The results
      indicate that hypertension induces a displacement to the right of the dose
      response curve to ACh in both adults and aged SJH-Rs; IC50 for adult rats was
      0.72 +/- 0.3 microM for SJH-Rs and 0.059 +/- 0.03 microM for MW (p < 0.05). Aged
      animals showed similar results: IC50 of 0.78 +/- 0.03 microM for SJH-Rs and of
      0.043 +/- 0.01 microM in age-matched MW rats (p < 0.025). However, no difference
      was observed between hypertensive (SJH-Rs) adult and aged animals. Similarly, no
      difference was observed between adult and aged MW control animals. The
      displacement of the dose-response curve to ACh in SJH-Rs appears to be associated
      with a reduced activation of NOS since in precontracted aortas from aged animals
      1 microM A23187 induced a relaxation of 51.2 +/- 12% in MW as compared with 34.4
      +/- 7% in SJH-Rs (n = 5, p < 0.05). These results indicate that endothelial
      dysfunction exists in SJH-Rs. The data suggest that an alteration of the
      endothelial NOS may be the cause of this abnormality. Finally, the magnitude of
      the endothelial dysfunction is not age dependent within the range evaluated.

PMID- 8761847
TI  - Comparative antigenicity of recombinant wild-type staphylokinase (SakSTAR) and a
      selected mutant (SakSTAR.M38) in a baboon thrombolysis model.
AB  - Staphylokinase, a bacterial plasminogen activator, is a potent, highly fibrin
      specific but antigenic thrombolytic agent in humans. In an effort to attenuate
      the antigenicity of wild-type staphylokinase (SakSTAR variant), 2 of its 3
      immunodominant epitopes were altered by substituting clusters of 2 or 3 charged
      amino acids with alanine, yielding the mutant SakSTAR.M38 (K35A, E38A, K74A,
      E75A, R77A), which was less antigenic in inbred New Zealand White rabbits. In the
      present study, groups of 6 baboons (Papio hamadryas) were randomized to SakSTAR
      (group 1) or SakSTAR.M38 (group 2). The thrombolytic potencies of 50
      micrograms/kg compound at baseline, assessed in an extracorporeal thrombosis
      model, were similar: 77 +/- 2.9% (mean +/- SEM) clot lysis in group 1 and 83 +/-
      3.6% in group 2. Groups 1 and 2 were immunized subcutaneously at 2, 3, and 5
      weeks with 500 micrograms SakSTAR or SakSTAR.M38, respectively. From 6 weeks,
      group 1 developed significantly more antibody-related neutralizing activity than
      group 2 (maximal titer at 8 weeks of 100 +/- 23 micrograms SakSTAR and of 22 +/-
      7.1 micrograms SakSTAR.M38 neutralized per milliliter of plasma, respectively).
      Neutralizing activities subsequently decreased gradually to 10-20% of peak values
      at 18 weeks. At 6 weeks, both groups were resistant to thrombolysis with 50
      micrograms/kg of either compound. Rechallenge at 18 weeks with 250 micrograms/kg
      of the immunizing compound showed a significantly better recovery of the
      thrombolytic potency of SakSTAR.M38 (68 +/- 4.5% clot lysis) than of SakSTAR (39
      +/- 5.3% clot lysis). Neither agent degraded fibrinogen or depleted alpha 2
      antiplasmin. Therefore, SakSTAR.M38 is comparably active and fibrin-specific but
      less antigenic than wild-type SakSTAR. These findings in outbred primates confirm
      and extend earlier observations in inbred rabbits and provide a basis for the
      further development of staphylokinase variants with reduced antigenicity in
      humans.

PMID- 8761848
TI  - Prevention of reoxygenation-induced arrhythmias in guinea pig papillary muscles.
AB  - Effects of various agents on reoxygenation-induced arrhythmias, action
      potentials, and tension of guinea pig papillary muscles were recorded to
      investigate the site of action. Triggered activities due to delayed
      afterdepolarizations (DADs) and aftercontractions were elicited on reoxygenation
      after 60-min substrate-free hypoxia. Low extracellular Ca2+ (0.1 mM) abolished
      arrhythmias, and high Ca2+ (4.9 mM) increased the amplitudes of DADs and
      aftercontractions. D-600 at the high concentration (20 microM) decreased the
      incidence of arrhythmias (p < 0.05 vs. no drug) and decreased the recovery of
      developed tension after reoxygenation (p < 0.001). Ryanodine (1 microM) abolished
      aftercontractions and arrhythmias but did not affect the recovery of developed
      tension. Tetrodotoxin (TTX 3 microM) and nicorandil (100 microM) decreased the
      incidence of arrhythmias (p < 0.05), but did not affect the recovery of developed
      tension or the amplitudes of aftercontractions. TTX caused only a slight decrease
      in Ca2+ transients in a fluo-3-loaded guinea pig ventricular myocyte. The Ca2+
      entry through the Ca2+ channels apparently synchronized Ca2+ release from the
      sarcoplasmic reticulum, and D-600 at the high concentration apparently decreased
      the incidence of arrhythmias. TTX and nicorandil decreased arrhythmias, probably
      by decreasing the Na+ current or by increasing the ATP-sensitive K+ current,
      respectively.

PMID- 8761849
TI  - Effect of E5510 on anastomotic intimal hyperplasia and platelet aggregation in
      dogs.
AB  - We examined the effect of an antiplatelet agent, E5510, which inhibits both
      platelet aggregation and release of platelet-derived growth factor (PDGF), on
      anastomotic intimal hyperplasia and platelet aggregation. Twenty Beagle dogs
      underwent infrarenal aortic reconstruction with an expanded
      polytetrafluoroethylene (ePTFE) graft 5 mm in diameter and 3 cm long. The dogs
      were divided into three groups: placebo (control group, 7 dogs), E5510 1 mg/day
      (1-mg group, 6 dogs), and E5510 4 mg/day (4-mg group, 7 dogs). E5510 was
      administered orally 2 h before operation and once daily for 3 months after
      operation. Grafts were harvested 3 months after operation. All 13 grafts in the
      treated groups remained patent without evidence of intimal hyperplasia, whereas
      only 4 of 7 grafts (57%) remained patent in the control group, including 1 graft
      with > 50% stenosis. Three occluded grafts showed severe intimal hyperplasia at
      the anastomoses. The platelet aggregation ratio (PAR) with collagen (100
      micrograms/ml) before drug administration at 3 months in the 4-mg group was
      significantly lower than that in the control and 1-mg groups. PAR after drug
      administration at 3 months in the 1- and 4-mg groups was significantly lower than
      that in the control group. Intimal thickness at the distal anastomosis was 817 +/
      190 microns in the control group, 240 +/- 80 microns in the 1-mg group, and 197
      +/- 28 microns in the 4-mg group. Intimal thickness in the control group was
      significantly greater than that in the 1- and 4-mg groups. Smooth muscle cell
      (SMC) values in the intima at the distal anastomosis were 65.6 +/- 4.4%
      extinction (%E) in the control group, 47.6 +/- 3.4%E in the 1-mg group, and 51.3
      +/- 3.5%E in the 4-mg group. SMC value in the control group was significantly
      greater than that in the 1- and 4-mg groups. E5510 inhibited PAR and reduced the
      degree of anastomotic intimal hyperplasia.

PMID- 8761850
TI  - KATP channel activation mediates nicorandil-induced relaxation of nitrate
      tolerant coronary arteries.
AB  - We compared the tolerance-inducing effects of nitroglycerin (NTG) and nicorandil
      (NIC) in porcine isolated coronary arteries and assessed the role of KATP
      channels in the response to NIC in nitrate-tolerant and nontolerant preparations.
      In coronary arteries contracted with U46619 (1-3 x 10(-9) M), NTG, NIC, sodium
      nitroprusside (SNP), and cromakalim produced concentration-dependent relaxations.
      The rank order of potency was NTG > or = SNP > cromakalim > nicorandil. Exposure
      of the rings to NTG (10(-4) M) for 90 min, followed by repeated rinsing for 1 h,
      produced a parallel, rightward shift of the subsequent concentration-response
      curves to NTG and SNP; a slight but significant reduction in the maximal response
      to NTG was also observed. Previous exposure to NTG had no effect on the NIC or
      cromakalim concentration-response curves. When the tissues were exposed to NIC (3
      x 10(-4) M) for 90 min, followed by repeated rinsing for 1 h, there was no effect
      on the subsequent concentration-response curves to NTG, NIC, SNP, or cromakalim.
      In both nitrate-tolerant and nontolerant coronary arteries, glibenclamide (GLI
      10(-6) M), a selective KATP channel blocker, caused a parallel rightward shift in
      the concentration-response curve to cromakalim, but had no effect on responses to
      NTG or SNP. In nontolerant coronary arteries, GLI had no effect on NIC-induced
      relaxation, but in nitrate-tolerant preparations, GLI produced a significant
      rightward shift in the NIC concentration-response curve. The results demonstrate
      that prolonged exposure to NTG, but not NIC, causes tolerance in isolated porcine
      coronary arteries and that the response to NIC is not affected by nitrate
      tolerance. The data also suggest that NIC-induced relaxation of nitratetolerant,
      but not nontolerant, coronary arteries is mediated by activation of KATP
      channels.

PMID- 8761851
TI  - Effects of vascular endothelial growth factor on hemodynamics and cardiac
      performance.
AB  - Vascular endothelial growth factor (VEGF), a major regulator of angiogenesis, has
      therapeutic benefit in animal models of coronary or limb ischemia. However, the
      hemodynamic effects of VEGF have not been investigated. We examined the effects
      of VEGF on hemodynamics and cardiac performance. Mean arterial pressure (MAP),
      heart rate (HR), cardiac output, stroke volume, left ventricular (LV) dP/dt, and
      hematocrit were measured before and after intravenous injection of VEGF in
      conscious, instrumented rats. VEGF caused a dose-dependent reduction in MAP and
      an associated increase in HR. VEGF (250 micrograms/kg) significantly decreased
      cardiac output and stroke volume without affecting the inotropic state of the
      left ventricle, as determined by dP/dt. VEGF significantly increased hematocrit.
      Furthermore, VEGF did not affect contractility or HR in the isolated rat heart in
      vitro. The data suggest that the VEGF-induced decrease in cardiac output is due
      to reduced stroke volume, which may be caused by a decrease in venous return
      rather than a direct effect on myocardial contractility. In addition,
      pretreatment with N omega-nitro-L-arginine methyl-ester (L-NAME), a nitric oxide
      (NO) synthase inhibitor, significantly attenuated the depressor and tachycardic
      responses to VEGF, suggesting that VEGF-induced hypotension may be mediated by
      NO.

PMID- 8761852
TI  - Mechanisms of vasorelaxant effect of dehydroevodiamine: a bioactive
      isoquinazolinocarboline alkaloid of plant origin.
AB  - We examined the mechanisms underlying the vasorelaxant effect of
      dehydroevodiamine (DeHE), one of the bioactive components of the Chinese herbal
      drug Evodia rutaecarpa that has been shown to produce vasorelaxant and
      hypotension. DeHE (10(-7)-10(-4) M) concentration-dependently relaxed isolated
      rat mesenteric arteries precontracted with phenylephrine (PE). This vasorelaxant
      potency was diminished by 15% by endothelial removal, L-NG-nitro arginine, or
      methylene blue (MB), but not indomethacin treatment, indicating that the
      vasorelaxant effect of DeHE was partially endothelium dependent and mediated by
      nitric oxide (NO) and the cyclic GMP pathway. In endothelium-denuded
      preparations, DeHE caused a rightward shift of the contractile concentration
      response curve (CRC) to PE in a dose-dependent manner with a pA2 value of 6.15.
      Maximal response was unaffected. Receptor binding assay indicated that DeHE
      competed with alpha 1-adrenoceptor ligand prazosin with a Ki value of 3.57
      microM. Potassium channel activity-attenuating conditions such as increased level
      of extracellular K+ (20 mM) and treatment with the antagonist tetraethylammonium
      (TEA) significantly inhibited DeHE's effect, suggesting a mode of action similar
      to that of a potassium channel activator. In addition, high concentrations of
      DeHE (3 x 10(-5) and 10(-4) M) relaxed high K+ (80 mM)-evoked contraction,
      indicating that DeHE might possess K+ channel blocking properties. Multiple
      action mechanisms, including endothelium dependence, alpha 1-adrenoceptor
      blockade, K+ channel activation, and Ca2+ channel blockade were probably involved
      in the vasorelaxant effects of DeHE.

PMID- 8761853
TI  - Serotonin-induced vasoconstriction in rabbit femoral artery: mediation by both 5
      HT2 serotonergic and alpha 1-adrenoceptors.
AB  - We determined the receptors mediating the contractile response of the rabbit
      femoral artery to serotonin in isolated vascular rings mounted in tissue baths
      for the measurement of isometric contraction. Serotonin elicited a biphasic
      concentration-response curve (CRC). The threshold and maximal concentrations of
      the first phase were 0.03 and 3 microM, respectively. The respective values for
      the second phase were 10 and 1,000 microM. Benextramine, a selective,
      irreversible alpha-adrenoceptor antagonist, eliminated the second phase. Similar
      results were obtained with benextramine in femoral arteries acutely denervated
      with 6-hydroxydopamine (6-OHDA). In contrast, the reversible, competitive 5-HT2
      antagonist ketanserin shifted the first phase of the serotonin CRC to the right
      ina concentration-dependent manner but had little or no effect on the second
      phase. No evidence for functional alpha 2-adrenoceptors was found. We conclude
      that the first phase of the serotonin CRC in rabbit femoral artery was mediated
      predominantly by 5-HT2 receptors and that the second phase was mediated by alpha
      1-adrenoceptors.

PMID- 8761854
TI  - Prolonging action of imidapril on the lifespan expectancy of cardiomyopathic
      hamsters.
AB  - We studied the effect of imidapril, a novel angiotensin-converting enzyme (ACE)
      inhibitor, on lifespan expectancy of cardiomyopathic (CM) hamsters of BIO 14.6
      strain, one of the representative models of congestive heart failure (CHF).
      Imidapril was consecutively administered to hamsters by mixing it in their diet
      at a concentration of 480 ppm (approximately 30 mg/kg/day) or 1,600 ppm
      (approximately 120 mg/kg/day) from age 26 weeks. Only several control hamsters
      died before age 54 weeks, but their survival rate decreased to 23.7% at age 73
      weeks. The survival rates of 480-ppm and 1,600-ppm imidapril groups at age 73
      weeks were as high as 75.7 and 68.4%, respectively (p < 0.01 vs. control
      hamsters). Macroscopic and microscopic pathology in imidapril-treated groups was
      milder than that in control animals in general, but differences were not
      statistically significant when animals were divided into survivors and fatalities
      except for the presence of mural thrombus in the heart. We further studied the
      effects of imidapril on blood pressure (BP), in vivo cardiac function, cardiac
      beta-adrenoceptor distribution, and plasma catecholamine levels after dietary
      treatment with 480 ppm imidapril for 8-10 weeks from age 37 weeks. Imidapril
      treated animals showed improved cardiac function under urethane anesthesia. These
      results indicate that imidapril prolongs lifespan expectancy of CM hamsters and
      suggest that a hemodynamic effect of imidapril is involved in its beneficial
      effect.

PMID- 8761855
TI  - ATP-stimulated release of ATP by human endothelial cells.
AB  - We investigated the effects of several concentrations of extracellular ATP on the
      release of intracellular ATP by human umbilical vein endothelial cells (HUVEC) in
      primary cultures. When ATP is added to the medium of cultured EC at a
      concentration of 1 microM, it is readily degraded by extracellular enzymes; 10
      microM ATP added to the culture medium provokes a transient but significant
      increase, followed by a decrease in the concentration of extracellular ATP. At a
      concentration of 100 microM, there was a significant release of ATP and its level
      was maintained in the culture medium throughout the experiment. Our results show
      that extracellular ATP leads to a sustained release of intracellular ATP by
      HUVEC. Such sustained self-perpetuating release of ATP is likely to play an
      important part in physiological and pathological local vascular control
      mechanisms.

PMID- 8761856
TI  - Effect of colchicine on circulating and myocardial neutrophils and on infarct
      size in a canine model of ischemia and reperfusion.
AB  - Myocardial injury after ischemia/reperfusion has been attributed in part to the
      effects of neutrophils. We examined whether colchicine, a potent and rapid
      inhibitor of neutrophils, may reduce inflammatory leukocytosis, prevent
      postischemic myocardial neutrophil accumulation, and reduce infarct size (IS).
      Twenty-four dogs were randomized to either a control (saline administration) or a
      colchicine (1 mg/kg intravenously, i.v.) group. Anesthetized open-chest dogs
      underwent 120-min coronary artery occlusion followed by 6-h reperfusion.
      Determinants of IS [area-at-risk (AAR) and collateral flow] and IS were measured
      in 22 dogs (11 in each group). We evaluated neutrophil toxicity by measuring ex
      vivo production of reactive oxygen species by chemiluminescence. Myocardial
      localization and accumulation of neutrophils were histologically evaluated by
      independent observers. The number of circulating neutrophils (p < 0.01),
      neutrophil cytotoxicity (p < 0.05), and neutrophil myocardial accumulation after
      6-h reperfusion (p = 0.006) were reduced in treated dogs. Left ventricular (LV)
      peak rate of pressure increase was similar in both groups during ischemia
      /reperfusion. However, whereas collateral blood flow and AAR, the main
      determinants of IS, were similar in control and treated dogs, there was no
      reduction in IS: 37.1 +/- 7% of AAR in controls and 37.4 +/- 8% in treated dogs.
      Despite marked reduction of neutrophil toxicity and postischemic myocardial
      neutrophil accumulation, no myocardial protection could be detected in this dog
      model.

PMID- 8761857
TI  - Effects of streptozotocin-induced diabetes on vascular reactivity in genetically
      hyperinsulinaemic obese Zucker rats.
AB  - Although the fa/fa Zucker rat shows many of the features of type II diabetes, the
      absence of consistent cardiovascular complications in this model may be due to
      the absence of significant hyperglycaemia. We studied the consequences of
      streptozotocin (STZ)-induced insulin deficiency and hyperglycaemia on vascular
      reactivity in the fa/fa Zucker rat. Hyperinsulinaemic obese Zucker rats were
      rendered diabetic by injection of STZ (50-60 mg/kg intraperitoneally, i.p.), and
      vascular tissue was removed for study 10-12 weeks later. In isolated aorta, there
      was no difference in the phenylephrine (PE) concentration-response relation
      between lean and obese control animals, but the concentration-response curve was
      shifted to the left in diabetic animals, (pD2 7.56 +/- 0.04 in STZ diabetic
      animals, n = 8; 7.4 +/- 0.04 in obese control, n = 9, p < 0.05). The maximum
      response was also enhanced in both aorta and perfused mesentery of STZ-treated
      animals. In contrast, the potency of serotonin (5-HT) in inducing contractions of
      isolated aorta were enhanced in tissues from obese as compared with lean animals
      (pD2 6.63 +/- 0.06, n = 9; 6.17 +/- 0.07, n = 7 respectively; p < 0.01) and was
      attenuated in animals with STZ-induced diabetes (pD2 6.31 +/- 0.09, n = 8, p =
      0.05). The differential effects of hyperglycaemia on PE-and 5-HT-induced
      vasoconstriction suggest that the long-lasting modulation of vasoconstrictor
      responses induced by increases in blood glucose level may be specific for some
      agonists.

PMID- 8761858
TI  - Mechanisms of the cardiovascular response to posterior hypothalamic nucleus
      administration of carbachol.
AB  - Unilateral microinjection of the cholinergic agonist carbachol (CCh) into the
      posterior hypothalamic nucleus (PHN) of conscious rats evoked a dose-dependent
      increase in mean arterial pressure (MAP). The pressor response was accompanied by
      tachycardia at all doses of CCh used (0.8-13.2 nmol), although the tachycardia
      was followed by a secondary bradycardia after the two highest doses (5.5 and 13.2
      nmol). To determine the involvement of the autonomic nervous system and arginine
      vasopressin (AVP) in these cardiovascular changes, we administered selective
      receptor antagonists intravenously (i.v.) before microinjection of CCh into the
      PHN. The pressor response evoked by 3.3 nmol CCh could be attenuated by prazosin
      (an alpha 1-adrenoceptor blocker) or yohimbine (an alpha 2-adrenoceptor blocker)
      and completely blocked by the combination of prazosin and yohimbine. In contrast,
      the increase in MAP evoked by 5.5 and 13.2 nmol CCh could be attenuated by
      prazosin, yohimbine, or D[(CH2)5Tyr(Me)]AVP (AVPX, a V 1-vasopressin receptor
      blocker), and completely blocked by the combination of prazosin and AVPX. The
      tachycardia evoked by the 3.3-, 5.5-, and 13.2-nmol doses of CCh could be
      attenuated by propranolol (a beta-adrenoceptor blocker), and the secondary
      bradycardia evoked by 5.5 and 13.2 nmol CCh could be attenuated by either
      methylatropine (a muscarinic receptor blocker) or AVPX. These results suggest
      that administration of CCh into the PHN increases sympathetic nervous system
      activity, which increases MAP and heart rate (HR). The increase in MAP activates
      a baroreflex-mediated bradycardia by increasing vagal tone. This bradycardia is
      potentiated by an increase in circulating levels of AVP, which also contributes
      to the increased blood pressure (BP).

PMID- 8761859
TI  - Calcitonin gene-related peptide does not mediate the abnormal vascular reactivity
      observed in a rat model of acute Pseudomonas pneumonia.
AB  - Abnormal systemic and pulmonary vascular reactivity has been demonstrated in
      numerous models of sepsis and pneumonia. Furthermore, the attenuated hypoxic
      pulmonary pressor response observed in these animals probably is responsible for
      the ventilation/perfusion (V/Q) mismatching and consequent arterial hypoxemia. We
      hypothesized that excess release of endogenous vasodilators such as calcitonin
      gene-related peptide (CGRP) in pneumonia was responsible for the diminished
      hypoxic pressor response. Using the CGRP receptor antagonist CGRP (8-37), we
      examined the role of CGRP in the attenuated hypoxic pulmonary response in a rat
      model of acute Pseudomonas pneumonia. Sixteen Sprague-Dawley rats were
      instrumented for chronic hemodynamic monitoring and subsequently randomized to
      either Pneumonia (n = 8), induced by the instillation of 0.2 ml broth containing
      2 x 10(8) colony-forming units (CFU)/ml Pseudomonas aeruginosa into the right
      lower lobe, or Sham (n = 8) procedure. Hemodynamic measurements and the hypoxic
      (FiO2 = 0.08) pulmonary pressor response were recorded at baseline, 48 h after
      the pneumonia or sham procedure and after the administration of 250 micrograms
      CGRP (8-37) (post-CGRP(8-37)). The regional distribution of pulmonary blood flow
      was determined by the injection of radioactive microspheres. Forty-eight hours
      after the instillation of Pseudomonas, Pneumonia animals had significantly
      increased cardiac output (CO) as compared with Sham (193 +/- 7 vs. 154 +/- 7
      ml/min, p < 0.05), slightly decreased mean arterial pressure (MAP 109 +/- 4 vs.
      118 +/- 3 mm Hg, p = NS), and reduced total systemic vascular resistance (TSVR
      0.57 +/- 0.03 vs. 0.78 +/- 0.05 mm Hg.min.ml-1, p < 0.05). Pneumonia animals were
      further characterized by increased mean pulmonary artery pressure (MPAP) as
      compared with Sham (24 +/- 2 vs. 20 +/- 1 mm Hg, p < 0.05) animals, and an
      increased alveolar-arterial (A-a) oxygen gradient (31 +/- 3 vs. 20 +/- 4 mm Hg, p
      < 0.05). The administration of CGRP (8-37) did not alter baseline hemodynamic
      variables and did not change the pressor response to hypoxia in either group.
      Furthermore, CGRP receptor blockade did not alter the distribution of blood flow
      in the lung during normoxia or hypoxia. These data suggest that although this
      model of acute pneumonia is characterized by an attenuated hypoxic pressor
      response, the mechanism does not appear to be mediated by excess release of the
      vasodilator CGRP.

PMID- 8761860
TI  - Role of nitric oxide in the attenuated pressor responses of pregnant or sodium
      deplete sheep.
AB  - Reduced pressor responsiveness to angiotensin II (Ang II) during pregnancy and
      sodium depletion is a well-known but little understood phenomenon; whether the
      same mechanisms are involved in both situations is unclear. In pregnant humans,
      altered vascular reactivity to norepinephrine (NE) has also been demonstrated.
      Nitric oxide (NO) has been implicated in the modulation of blood pressure (BP)
      and the maintenance of vascular tone and may be involved in these attenuated
      responses. We examined the role of NO in the pressor responses to (a) Ang II (5,
      10, 25, 50 micrograms/h) and NE (0.32, 0.65, 1.62, 3.24 mg/h) in pregnant and
      postpartum sheep, and (b) to Ang II (5, 7, 5, 10, 25, 50 micrograms/h) in sodium
      replete sheep and sheep made sodium deplete by 24 h of parotid salivary drainage.
      Vascular NO production was inhibited by pretreatment with N omega-nitro-L
      arginine (NOLA 10 mg/kg), a NO-synthase inhibitor. Pregnancy significantly
      reduced (p < 0.001) pressor responses to Ang II, which ranged from 5.1 +/- 0.2
      30.6 +/- 1.2 mm Hg as compared with postpartum increases of 10.3 +/- 0.5-52.2 +/-
      3.4 mm Hg. Pretreatment with NOLA partially restored Ang II responses to
      postpartum levels. Pregnancy did not alter pressor responses to NE. Sodium
      depletion also significantly reduced responses to Ang II by the same amount as in
      pregnancy, and these responses returned to normal with pretreatment with NOLA. NO
      thus has a role in modulating the attenuated pressor responses to Ang II in
      pregnant and sodium-deplete sheep.

PMID- 8761861
TI  - Quinidine pharmacodynamics in normal and isoproterenol-induced hypertrophied
      blood-perfused working rabbit hearts.
AB  - Ventricular hypertrophy is associated with several electrophysiologic
      abnormalities. However, little is known about the pharmacodynamics of
      antiarrhythmic drugs in the setting of ventricular hypertrophy. We studied the
      myocardial accumulation and pharmacodynamics of quinidine in 10 control rabbit
      hearts and 10 with isoproterenol-induced hypertrophy. Hearts were perfused in the
      working heart configuration. Electrophysiologic measurements were made at low
      afterload (30 cm H2O) and high afterload (60 cm H2O) at baseline and during
      quinidine perfusion (972 ng/ml). The myocardial quinidine concentration measured
      at the end of each experiment was significantly lower in the hypertrophied hearts
      (25.0 +/- 11.7 micrograms/g) as compared with the control hearts (51.2 +/- 12.7
      micrograms/g, p < 0.001). The left ventricular (LV) monophasic action potential
      (MAP) duration was significantly shorter in the hypertrophied hearts as compared
      with control hearts at low afterload (166 +/- 27 vs. 192 +/- 24 ms, p < 0.01) and
      at high afterload (141 +/- 7 vs. 171 +/- 24 ms, p < 0.01). Quinidine prolonged
      MAP duration to a similar extent in both hypertrophied and control hearts; the
      MAP prolongation occurred at both low (192 +/- 21 vs. 223 +/- 25 ms, p < 0.02)
      and high afterloads (179 +/- 15 vs. 216 +/- 20 ms, p < 0.01) in the hypertrophied
      and control hearts, respectively. However, the ratios of the changes in
      electrophysiologic parameters to quinidine myocardial concentrations were greater
      in the hypertrophied hearts than in control hearts (p < 0.05). Therefore, AP
      duration (APD) is significantly shortened in isoproterenol-induced hypertrophy.
      The magnitude of quinidine effects on MAP duration and ventricular effective
      refractory period (VERP) are similar in hypertrophied hearts and control hearts,
      but the myocardial concentration-effect relations are increased significantly in
      hypertrophied hearts.

PMID- 8761862
TI  - Experimental study of self-expandable metallic inferior vena caval stent crossing
      the renal vein in rabbits. Radiologic-pathologic correlation.
AB  - RATIONALE AND OBJECTIVES: The authors evaluate in the rabbit the radiologic
      pathologic changes of the inferior vena cava and the renal vein and the
      functional changes of the kidneys after placement of a self-expandable metallic
      stent in the inferior vena cava where the renal vein empties. METHODS: One self
      expandable metallic stent was placed in the inferior vena cava in each of 12
      rabbits; the rabbits were divided into four groups of three rabbits each. The
      inferior vena cava and renal vein were examined angiographically and
      pathologically at intervals of 1 week, 2 weeks, 1 month, and 3 months. Vena
      cavography was performed to evaluate changes in the inferior vena cava before and
      after stenting. Laboratory tests were performed to determine blood urea nitrogen
      and creatinine levels, and radioisotope renal scans were performed to evaluate
      possible changes in renal function before and after stenting. RESULTS: No stent
      migration was noted in 11 of 12 rabbits; however, migration of the stent to the
      subdiaphragmatic level was noted in 1 rabbit. All stents were patent
      angiographically. Statistical analysis showed no significant change in renal
      function after stenting (blood urea nitrogen, P = 0.9; creatinine P = 0.5). In
      addition, radioisotope scans revealed no abnormal findings in perfusion and
      excretion. Pathologic examination of both kidneys showed no abnormal findings.
      Neointimal proliferation over the stent was first noted at 1 week after the stent
      was placed, was most prominent at 1 month, and regressed substantially by 3
      months. CONCLUSIONS: The self-expandable metallic stent was relatively well
      adapted to the inferior vena cava. Renal function was not affected by the
      inferior vena cava stent, which crossed the orifice of renal vein.

PMID- 8761863
TI  - Interpretation variability of 18FDG-positron emission tomography studies in
      dementia.
AB  - RATIONALE AND OBJECTIVES: Functional imaging studies such as 18F-fluoro-18
      labeled-deoxyglucose-positron emission tomography (18FDG-PET) are being used
      increasingly in the evaluation of patients with dementia. The authors evaluate
      inter- and intraobserver interpretation agreement in a diverse group of patients
      with clinically diagnosed dementia and subjective memory complaints, as well as
      two healthy control subjects. METHODS: Ninety-six patients with clinical
      diagnoses of probable Alzheimer's disease (n = 18), possible Alzheimer's disease
      (n = 33), dementia (n = 26), and mild memory impairment (n = 17), as well as two
      healthy control subjects were studied using 18FDG-PET. Three observers graded all
      studies for regional 18FDG uptake in the temporal, parietal, and frontal regions
      bilaterally. The studies also were interpreted for the presence of bilateral
      temporoparietal hypometabolism, which typically is present in Alzheimer's
      disease. The kappa statistic was used to determine intra- and interobserver
      agreement for regional 18FDG uptake and bilateral temporoparietal hypometabolism.
      RESULTS: There was excellent intraobserver (kappa = .56, P < 0.0005) and
      interobserver (kappa = .51, P < 0.0005) interpretation agreement for bilateral
      temporoparietal hypometabolism. There also was excellent intraobserver (kappa =
      .61, P < 0.000) and interobserver (kappa = .55, P < 0.000) interpretation
      agreement of regional 18FDG uptake. Interobserver agreement was extremely high in
      those patients who were considered clinically to have possible (kappa = .42, P <
      0.001) or probable (kappa = .42, P < 0.01) Alzheimer's disease. CONCLUSIONS:
      Results confirm that bilateral temporoparietal hypometabolism is the metabolic
      abnormality associated with the diagnosis of probable Alzheimer's disease.
      Furthermore, intra- and interobserver agreement of visual interpretation of 18FDG
      PET images indicates that 18FDG-PET is acceptable as an imaging technique in the
      clinical evaluation of the dementia patient.

PMID- 8761864
TI  - A quantitative study of ramped radio frequency, magnetization transfer, and slab
      thickness in three-dimensional time-of-flight magnetic resonance angiography in a
      patient population.
AB  - RATIONALE AND OBJECTIVES: The authors compare the effectiveness of various
      magnetic resonance (MR) angiography acquisition strategies in enhancing the
      visibility of small intracranial vessels. METHODS: Blood vessel contrast-to-noise
      ratio (CNR) in time-of-flight MR angiography was studied as a function of vessel
      size and several selectable imaging parameters. Contrast-to-noise measurements
      were made on 257 vessel segments ranging in size from 0.3 mm to 4.2 mm in
      patients who recently had undergone intraarterial cerebral angiography. Imaging
      parameters studied included magnetization transfer, spatially variable radio
      frequency (RF) pulse profile (ramped RF), and imaging slab thickness. RESULTS:
      The combination of thin slabs (16 slices/slab), ramped RF, and magnetization
      transfer resulted in the highest CNR for all but the smallest vessel sizes. The
      smallest vessels (< 0.5 mm) had the highest CNR, using the thick slab (64
      slices/slab) with ramped RF and magnetization transfer. Magnetization transfer
      always improved vessel CNR, but the improvement diminished as the slab thickness
      was reduced. The CNR increased with a decrease in slab thickness for all but the
      smallest vessel sizes. CONCLUSIONS: Overall, the results provide a quantitative
      demonstration that inflow enhancement of blood is reduced for small vessels.
      Thus, whereas magnetization transfer is important at all vessel sizes, it becomes
      the primary factor in improving the visibility of the smallest vessels.

PMID- 8761865
TI  - The accuracy of computed tomography-based linear measurements of human femora and
      titanium stem.
AB  - RATIONALE AND OBJECTIVES: The authors investigate the accuracy of computed
      tomography linear measurement of femora with titanium stem, and the effect of the
      stem on these measurements. MATERIALS AND METHODS: Two embedded cadaveric femora,
      one of them containing a titanium stem, and two cortical bone parallelepipeds
      were scanned. Thirty-six cross-sections were studied, each measured in two linear
      directions by the profile window technique. A half-maximum height method was used
      to determine the cortex-gap-titanium sizes from the computed tomography (CT)
      images. The accuracy of the measurements from the parallelepipeds, femora, and
      titanium stem taken from the CT was compared with those taken by a digital
      caliper of anatomical sections at the same level of the same bone. RESULTS:
      Computed tomography measurements of the parallelepipeds were similar to the
      anatomical size (mean relative error 0.04% +/- 0.63%). The mean error and mean
      relative error of the cadaveric femora CT with and without the stem were similar
      to the control parallelepipeds. Higher values of error were found for the
      titanium stem. CONCLUSIONS: The half-maximum height method in the profile window
      provides an accurate measurement of the femoral cortex and the titanium stem. The
      presence of the titanium stem in the medullary cavity of the femur did not
      interfere with the measurements of cortical dimensions.

PMID- 8761866
TI  - Neurotolerability of nonionic X-ray contrast media. The role of chemotoxicity.
AB  - RATIONALE AND OBJECTIVES: Because small quantities of x-ray contrast agents can
      cross the blood-brain barrier, the authors evaluate the properties that
      contribute to neurotoxicity. METHODS: The acute toxicity of various monomer and
      dimer contrast media was assessed after intracerebroventricular (ICV) injection
      to mice and intracisternal (ICI) injection to rats. RESULTS: In mice, median
      lethal dose (LD50) values for monomer contrast media apart from iohexol were
      higher than those for dimer contrast media. In rats, iopentol and iopromide were
      more neurotoxic than all other contrast media. The signs of toxicity for all
      contrast media included convulsions, dyspnea, hypoactivity, and sedation.
      Hypertonic D-mannitol solution was tolerated as well as artificial cerebrospinal
      fluid. Neither the hydrophilicity of the molecules nor the physicochemical
      properties of their solutions explain the toxicities satisfactorily. CONCLUSIONS:
      Neurotoxicity of monomer or dimer contrast media depends more on chemical
      structure characteristics other than hydrophilicity than on the physicochemical
      characteristics of their solutions.

PMID- 8761867
TI  - Observation of metabolic changes in chronic schizophrenia after neuroleptic
      treatment by in vivo hydrogen magnetic resonance spectroscopy.
AB  - RATIONALE AND OBJECTIVES: The authors investigate: (1) whether there is a lateral
      effect of hydrogen (1H) magnetic resonance (MR) spectroscopy observable
      metabolite ratios between the right and the left prefrontal lobe in chronic
      schizophrenia; (2) whether there is a change of proton metabolite ratios in
      chronic schizophrenia after neuroleptic treatment; (3) whether there is a
      relation between changes in 1H MR spectra and the clinical assessment of Brief
      Psychiatric Rating Scale (BPRS); and (4) to investigate a hypofrontality
      hypothesis in schizophrenia in terms of neurochemical aspects. METHODS: Localized
      in vivo 1H MR spectroscopy was used to measure the metabolite levels in the
      prefrontal lobes of control persons (n = 20) and of chronic patients before and
      after neuroleptic treatment (n = 34). The MR spectra of 8 cm3 voxels were
      compared with clinical assessment of BPRS in each subject. RESULTS: No
      significant metabolic lateral effect was established in both schizophrenia and
      control groups (P > 0.05). After neuroleptic treatment, chronic schizophrenic
      patients generally demonstrated a decrease of the complex of gamma-aminobutyric
      acid (GABA) and glutamate (Glu) containing (GABA + Glu)/creatine (Cr) ratio.
      CONCLUSIONS: The current follow-up 1H MR spectroscopy study shows a significant
      correlation between alterations of (GABA + Glu)/Cr ratio and BPRS, and supports a
      hypofrontality hypothesis in chronic schizophrenia. The reduction of (GABA +
      Glu)/Cr ratio after neuroleptic treatment may implicate the recovery of normal
      neuronal function in neurotransmitters. In vivo 1H MR spectroscopy may be a
      useful modality in follow-up evaluation of neuroleptic treatment in chronic
      schizophrenia.

PMID- 8761868
TI  - Experimental acute cerebral ischemia with reperfusion. Evaluation with gadolinium
      texaphyrin.
AB  - RATIONALE AND OBJECTIVES: The authors explore the potential usefulness of the new
      contrast medium gadolinium (Gd)-texaphyrin (PCI-0101) in magnetic resonance
      imaging of experimental acute cerebral ischemia with reperfusion. METHODS: Four
      New Zealand white rabbits underwent 2 hours of transorbital occlusion of the left
      internal carotid, anterior, and middle cerebral arteries, followed by 2 hours of
      reperfusion with normal saline. Immediately thereafter, the rabbits were injected
      with 25 mumol/kg of 2 mmol/L Gd-texaphyrin and killed by barbiturate overdose.
      Postmortem T1- and T2-weighted coronal scans were performed at 1.5 Tesla and
      correlated with histopathologic findings. RESULTS: Postcontrast T1-weighted
      images showed high signal within extensive cortical and basal ganglia infarcts.
      Areas of high signal on T1-weighted images were less extensive than on T2
      weighted images, and corresponded to only a portion of the region of neuronal
      damage seen histologically. Signal intensity of infarcted brain on postcontrast
      T1-weighted images was significantly greater than normal brain in the
      contralateral hemisphere (P < 0.0014). CONCLUSIONS: Experimental reperfused
      infarcts only 2 hours old demonstrate contrast enhancement with Gd-texaphyrin.

PMID- 8761869
TI  - Magnetic resonance imaging of isolated skeletal muscles. Osmotic influence.
AB  - RATIONALE AND OBJECTIVES: The authors evaluate the contribution of intracellular
      water to the change of T2 relaxation time. METHODS: Magnetic resonance images of
      frog muscles (n = 16) were obtained in hypotonic, isotonic, and hypertonic
      solutions, and their leg weights and T2 relaxation times were measured. Likewise,
      these values were measured after electric stimulation for 2 to 10 minutes in
      isotonic solution (n = 5). RESULTS: The muscle weights increased in the hypotonic
      solutions, whereas they showed no change in isotonic solution. T2 relaxation
      times, however, showed little change in either isotonic or hypotonic solutions.
      In electrically stimulated muscles, T2 relaxation times increased, accompanying
      the increase in muscle weight in isotonic solutions. CONCLUSION: Muscle
      contraction results in increased T2 relaxation time, but intracellular water
      hardly contributes to the increase in this value. Therefore, an increase in
      extracellular water may be the main cause of the increase in T2 relaxation time
      seen in exercised muscles.

PMID- 8761870
TI  - Differentiation of delayed kidney graft function with gadolinium-DTPA-enhanced
      magnetic resonance imaging and Doppler ultrasound.
AB  - RATIONALE AND OBJECTIVES: The authors differentiate acute tubular necrosis from
      transplant rejection in patients with delayed kidney graft function using
      gadolinium (Gd)-DTPA enhanced magnetic resonance (MR) imaging. METHODS: Twenty
      four patients after renal transplantation (10 with normal graft function, 14 with
      delayed graft function) underwent conventional and Doppler sonography and MR
      imaging examination after bolus application of Gd-DTPA. Within a time period of
      512 seconds, 39 single-slice MR images were obtained. Measurements of signal
      intensity in three regions of interests (cortex, medulla, renal pelvis) resulted
      in a graphic description of the dynamics of the contrast enhancement. The time
      between the start of the scan and the peaks of the curves was measured. RESULTS:
      In patients with normal graft function the curves reached the peaks between 39
      and 55 seconds (cortex), 44 and 61 seconds (medulla), and between 161 and 318
      seconds (renal pelvis). Six patients with acute tubular necrosis showed normal
      values for the curves 1 and 2 but markedly prolonged time for curve 3 (between
      420 and 512 seconds). In all patients with histologically proven transplant
      rejection, the peaks of all curves were not reached before the ends of the scans.
      CONCLUSION: The authors' preliminary results suggest that MR imaging seems to be
      a sensitive, noninvasive diagnostic tool to differentiate acute tubular necrosis
      from transplant rejection in the critical early postoperative period.

PMID- 8761871
TI  - Renal tolerance of nonionic dimers.

PMID- 8761872
TI  - Technetium-99m-ethylenedicysteine in the diagnosis and follow-up of renovascular
      hypertension.
AB  - Technetium-99m-ethylenedicysteine (99mTc-EC) captopril scintigraphy performed in
      a patient with severe hypertension revealed increased parenchymal retention in
      the left kidney, suggesting renal artery stenosis. After angiographic
      confirmation of renal artery stenosis, percutaneous transluminal angioplasty
      (PTA) was performed on the left renal artery. Captopril scintigraphy after PTA
      showed normal findings with no evidence of parenchymal retention, consistent with
      reversal to normal kidney functions. In light of this case of renal artery
      stenosis, it was concluded that 99mTc-EC can be used successfully as a potential
      renal agent in the diagnosis and follow-up of renovascular hypertension.

PMID- 8761873
TI  - [Surgery for severe traumas of the kidney. Value of initial computed tomography,
      problem of surgical indication and use of a perirenal resorbable prosthesis of
      polyglactin 910].
AB  - We report our recent experience in the surgical treatment of severe closed renal
      trauma, describing the value of the initial tomography scan, the problems
      encountered with indications for surgery, and use of a resorbable peri-renal
      prosthesis made of polyglactine 910. During the last 4 years, 41 patients were
      hospitalized for renal trauma. Eleven of these patients were operated for severe
      lesions (Chatelain stage 3 and 4). Surgical treatment was as conservative as
      possible: total organ repair was possible in 5 cases and partial repair in 3, the
      kidney was lost in 3 cases.

PMID- 8761874
TI  - [Treatment of stress urinary incontinence in women using the Goebell-Stoeckel
      surgical method. Study of 59 operated patients. Long-term review].
AB  - Stress urinary incontinence may be treated by different techniques. This study is
      based on a retrospective analysis of 59 patients treated between 1985 and 1993,
      by the Goebell-Stoeckel technique. 48 patients were questionned by phone in March
      1995 to estimate the long term results. Two groups were defined; group A: follow
      up between 15-60 months and group B: follow-up between 72-120 months (Total
      average follow-up: 68 months). The majority of patients were elderly, menopaused
      (88%) and had had one or more surgical procedure for incontinence (60%). Among 59
      patients, 8 developped minor early complications. The mean length of hospital
      stay was 14 days and the mean duration of indwelling catheterization was 6.5
      days. 60% of patients have had urinary retention after catheter ablation and have
      required intermittent catheterization at home for a mean duration of 14 days.
      Continence was achieved in 84% of cases at 3 months and had persisted in 96% of
      cases for group A and 91.5% of cases for group B. With a mean follow-up of 68
      months, 37.5% of cases had irritative symptoms, 12.5% had minor urethral
      obstruction. 52% of patients obtained a very excellent result (normal continence,
      no urgency, no dysuria), 9% obtained an excellent result (normal continence,
      urgency with no leaked, and/or minor dysuria); 12 obtained a moderate result
      (normal continence, urgency with minor leakage without toilet set, and/or minor
      dysuria) and 27% obtained a poor result (incontinence, urgency with leakage
      necessitating toilet set, and/or dysuria).

PMID- 8761875
TI  - [Internal urinary diversion in pelvic cancers and quality of life. Value of
      double "J" endoprosthesis].
AB  - The ureteral double pigtail stents are versatile and valued for proper urinary
      drainage in the setting of trauma, fistula formation, after extra-corporeal shock
      wave lithotripsy (ESWL) and surgical manipulations of the upper urinary tract.
      Also they are used for prolonged urinary drainage in patients with chronic tumor
      induced ureteral obstruction, and present an exceptional patient tolerance. The
      authors' experience is based upon 54 patients treated for ureteral obstruction of
      malignant origin between January 1989 and October 1995. Complications of this
      method as well as the quality of life of these patients are analysed and the
      results compared with those of the literature. The patient tolerance was
      excellent. Mean survival time after ureter catheterisation was 18 months.
      Complete urine diversion was achieved and hydronephrosis disappeared soon after
      stent placement in 42 patients (80%). In addition hydronephrosis persisted in 12
      cases (20%), despite orthotopic positioning of the catheter and numerous stent
      changes for larger caliber stents. The palliative use of the double pigtail stent
      when no other treatment is possible for malignant ureteral obstruction, precludes
      the need for ureterostomy and offers the patient a comfortable quality of life.
      Bladder disease is a contraindication to the use of these catheters, although
      their insertion is rarely impossible. In case of acute obstruction, it is better
      to prepare the pathway with a standard ureteral catheter, which is easier to
      manage. It is always possible to insert the pigtail stent after some time has
      elapsed.

PMID- 8761876
TI  - [Vascular complications of kidney transplantation].
AB  - We report a retrospective analysis of 100 renal transplantations, mainly from
      related living donors. The rate of vascular complications was 9%: one arterial
      hemorrhage due to partial suture failure; one lymphocele; two arterial thrombi,
      one in the inferior artery leading to fistulization by ureteral necrosis and
      death following septic rupture of the artery, and one in the renal artery
      requiring graft removal; and five arterial stenoses, one which regressed
      spontaneously, one treated by endoluminal angioplasy, one treated surgically, one
      controlled by medical treatment and one which could not be treated due to
      secondary hemodialysis after graft rejection. In this series of 100
      transplantations, vascular complications were the cause of 16.5% of deaths and
      12.5% of post-graft hemodialysis.

PMID- 8761877
TI  - [Two-stage surgical treatment of urethral stenosis].
AB  - We analysed the results of two-operation procedures for cutaneous urethroplasty
      performed over a 10 year period. From 1983 to 1993, 44 patients had a Leadbetter
      urethroplasty. The indication in all cases was stenosis of the bulbal or
      bulbomenbranous urethra complicated by urethro-cutaneous fistula. After the first
      operation, 10 patients (22.7%) had a stenosis of one or both of the urethrostomy
      orifices, requiring one or more further procedures. The second operation
      concerned 18 patients (40.9%) and gave goods results in 10 (55.5%). Poor results
      were due to recurrence of the stenosis in 3 cases (16.6%), perineal suppuration
      in 1 (5.5%), failure of the skin plasty in 1 (5.5%) and formation of a stenosis
      by a tuft of hair in 1 (5.5%). Finally, 2 patients were lost to follow-up. Mean
      interval between operations was 8 months. It appears, despite the drawbacks and
      uncertain results, that sequential operations for cutaneous urethroplasty are
      indicated when stenosis of the urethra is complicated by fistulization or
      perineal infection.

PMID- 8761878
TI  - [Sclerotherapy with Betadine for simple cysts of the kidney. Apropos of 7 cases].
AB  - The authors report on 7 cases of benign, symptomatic renal cysts treated by
      percutaneous sclerosis using Betadine solution. The mean size of the cysts was 8
      cm and we obtained progressive collapse of all of them. This technique was a
      simple and effective methode with good results. Indeed, 85% of the cysts
      disappeard, and only one patient retained a small asymptomatic residual cavity.

PMID- 8761879
TI  - [Trans-symphyseal approach in the treatment of cervico-urethro-vaginal fistulas.
      Apropos of 2 cases].
AB  - We opted for a symphysiotomy approach in the management of cervico-urethro
      vaginal fistulae in two patients. This approach offers an excellent exposure of
      the region of the bladder neck. After section of the symphysis pubis with a
      Gigli's wire saw, the anterior wall of the bladder was taken down to the fistulae
      and we excised the fistulous tract. Longitudinal closure of the fistulae and the
      bladder followed. Results were satisfactory and there were no urinary
      incontinence.

PMID- 8761880
TI  - [Female hypospadias. Apropos of 3 cases].
AB  - Female hypospadias (FH) is a rare congenital abnormality caracterised by total or
      partial agenesy of uretero-vaginal septum. We report there cases of this anomaly.
      In one case, FH was isolated. In the others two, it was associated with other
      genital abnormalities. The diagnosis was established in adult age. Urinary
      incontinence is the most constant revealing symptom. Treatment consists of an
      uretral reconstruction using the anterior wall of vagina. In one case, associated
      vaginal atresia was treated during the same operation. Perfect continence and
      good bladder emptying was noted in two cases. One patient had been reoperated to
      perfect the continence.

PMID- 8761881
TI  - Cocaine exposure during the brain growth spurt failed to produce cerebellar
      Purkinje cell loss in rat pups.
AB  - Previous studies in our laboratory indicated that cocaine exposure during the
      brain growth spurt period, a developmental stage vulnerable to various
      teratogens, did not produce microencephaly (gross brain weight measures).
      However, neonatal cocaine exposure has been shown to affect motor coordination
      and balance, which are both sensitive to cerebellar damage. The purpose of this
      study was to investigate whether cocaine exposure during the brain growth spurt
      period could result in the loss of cerebellar Purkinje cells, a neuronal
      population known to be vulnerable to other teratogenic insults. Sprague-Dawley
      rat pups were randomly assigned to either cocaine-treated groups (40, 80 mg/kg
      s.c.) or a gastrostomy control group, and were reared using an artificial-rearing
      method from postnatal days (PDs) 4 through 9. On PD 10, these animals were
      perfused and the cerebella were extracted and processed for cell counts.
      Estimates of Purkinje cell numbers were obtained using a 3-dimensional optical
      dissector method. The results using this stereological method demonstrated no
      significant Purkinje cell loss in response to cocaine treatment, even at a dose
      which has been shown to result in high mortality. The failure of cocaine to
      produce significant Purkinje cell loss (present finding) or microencephaly
      (previous finding) odds to the evidence indicating that cocaine is not a potent
      neuroteratogen.

PMID- 8761882
TI  - Patterned expression in familial Klippel-Feil syndrome.
AB  - Klippel-Feil syndrome (KFS) is characterised by congenital fusion of vertebrae
      within the rostral spine. The first KFS gene (SGM1) locus identified on
      chromosome 8 segregates with vertebral fusions and associated vocal impairment
      within the KF2-01 family (Clarke et al., '94, '95). Here, we describe the unique
      pattern of variable phenotypic expression within the KF2-01 family. The pattern
      of anomalies revealed a cumulative, rostrocaudal graded sequence of skipped
      vertebral fusions. This fusion pattern presents striking similarities with the
      mutant phenotype and gene expression profile of the Drosophila segment polarity
      gene engrailed.

PMID- 8761883
TI  - Pattern of retinoid-induced teratogenic effects: possible relationship with
      relative selectivity for nuclear retinoid receptors RAR alpha, RAR beta, and RAR
      gamma.
AB  - Retinoic acid, an oxidative metabolite of vitamin A, is involved in the control
      of many biological processes including embryonic development. Excess as well as
      deficiency of retinoids were found to be teratogenic. The effects of retinoids in
      normal as well as abnormal development may be mediated by two members of retinoid
      receptors, the RAR's and RXR's, which exhibit a specific temporal and spatial
      expression during development. The significance of the retinoid receptors was
      investigated here by studying the teratogenic effects of retinoid ligands with
      relative selectivity for binding and transactivation of the retinoic acid
      receptors RAR alpha, RAR beta and RAR gamma. Pregnant NMRI mice were administered
      5 or 15 mg/kg of CD 336 (Am 580) (alpha-ligand), CD 2019 (beta-ligand), CD 437
      (gamma-ligand) or 37.5 mg/kg all-trans-retinoic acid in 25% Cremophor EL on day
      8.25 or day 11 of gestation by gastric intubation. External, visceral and
      skeletal malformations were observed on day 18 of gestation. The order of
      teratogenic potency was: alpha-ligand > beta-ligand > gamma-ligand. In addition,
      these retinoids also produced a different spectrum of defects. The alpha-ligand
      induced the most varied defects including severe ear, mandible, and limb
      malformations. The beta-ligand induced defects of the urinary system and liver in
      greater frequency than expected from its relative potency. The gamma-ligand
      preferentially induced ossification deficiencies and defects of the sternebrae
      and vertebral body. Our results show that these three retinoids, which were
      previously demonstrated to exhibit retinoid-like activities in several systems,
      exert differing teratogenic activities, in regard to both potency and
      regioselectivity: we hypothesize that the relative selectivity for binding and
      transactivation of the three retinoic acid receptors could possibly be related to
      the differences of teratogenic effects observed in this study. The low potency of
      the gamma-ligand may lead the way to interesting new retinoids with improved
      therapeutic ratio.

PMID- 8761884
TI  - Teratogenic potential of almokalant, dofetilide, and d-sotalol: drugs with
      potassium channel blocking activity.
AB  - Drugs with class III antiarrhythmic activity are potential human teratogens
      because of their ability to cause bradycardia in the embryo during the
      organogenic period. Three drugs with class III antiarrhythmic activity,
      almokalant, dofetilide and d-sotalol, were compared in vitro using rat embryo
      culture. Each of these drugs caused a concentration-dependent bradycardia in 11-
      or 13-day rat embryos. For each drug the effective concentration was considerably
      greater than the human therapeutic plasma concentration. The reproductive outcome
      was also compared in vivo in Sprague-Dawley rats by oral administration of
      almokalant or dofetilide on single days during the organogenic period. Both drugs
      caused increased resorptions and the same stage-dependent malformations. Dosing
      on gestational day (GD) 11 was associated with right-sided oblique cleft lip and
      short tail, while dosing on day 13 caused digital hypoplasia and/or amputation.
      Susceptibility to these drugs started on GD 9 when the embryonic heart starts
      beating and ended on GD 15. The malformations were preceded by hemorrhage; which
      is consistent with the proposed pathogenesis that the drug-induced bradycardia
      caused embryonic hypoxia/ischemia. This study indicates that the induction of
      malformations/embryonic death by class III antiarrhythmic drugs which inhibit Ikr
      is a class effect secondary to a common pharmacological action on the embryonic
      heart.

PMID- 8761885
TI  - Maternal phenylketonuria: a metabolic teratogen.
AB  - The maternal phenylketonuria (PKU) syndrome refers to the teratogenic effects of
      PKU during pregnancy. These effects include mental retardation, microcephaly,
      congenital heart disease, and intrauterine growth retardation. In untreated
      pregnancies wherein the mother has classic PKU with a blood phenylalanine level >
      or = 1,200 microM (20 mg/dl), the frequencies of these abnormalities in offspring
      are exceedingly high, approaching 75-90% for microcephaly and mental retardation
      and 15% for congenital heart disease. There is a dose response relationship with
      progressively lower frequencies of these abnormalities at lower phenylalanine
      levels, both in the pregnancies of women with variants of PKU and in treated
      classic PKU pregnancies. The pathogenesis of this syndrome is unknown; it may be
      related to inhibition by phenylalanine of large neutral amino acid transport
      across the placenta or to direct toxicity of phenylalanine and/or a phenylalanine
      metabolite in certain fetal organs. A mouse model for PKU now exists, and studies
      of maternal PKU in this model are in progress. The treatment of maternal PKU
      consists of biochemical control through a phenylalanine restricted diet during
      pregnancy. The best results are obtained with diet initiation before conception
      or no later than the earliest weeks of pregnancy. Women with PKU and their
      families require much psychosocial support to meet the strict requirements of a
      maternal PKU pregnancy, including compliance with a difficult diet. With such
      compliance, however, it seems that bearing normal or near normal offspring is
      possible.

PMID- 8761886
TI  - Reproductive toxicity testing of therapeutic biotechnology agents.

PMID- 8761887
TI  - Reactive oxygen species in developmental toxicity: review and hypothesis.

PMID- 8761888
TI  - The role of stress management in blood pressure control: why the promissory note
      has failed to deliver.

PMID- 8761889
TI  - Stress management in hypertension.

PMID- 8761890
TI  - Nitroxidergic nerve: regulation of vascular tone and blood flow in the brain.

PMID- 8761891
TI  - Plasma membrane calcium pump-mediated calcium efflux and bulk cytosolic free
      calcium in cultured aortic smooth muscle cells from spontaneously hypertensive
      and Wistar-Kyoto normotensives rats.
AB  - OBJECTIVE: To compare the efficacy of the calcium pump-mediated calcium efflux
      pathway in spontaneously hypertensive rats (SHR) with that in Wistar-Kyoto
      normotensive rats (WKY), at rest and after angiotensin II stimulation. DESIGN:
      The intracellular free calcium concentration and calcium-45 efflux were measured
      in parallel, in cultured aortic smooth muscle cells isolated from 10-week-old
      male SHR and WKY rats. METHODS: The intracellular free calcium concentration and
      calcium-45 efflux were studied in confluent vascular smooth muscle cells in
      culture. Experiments were performed in the absence of added extracellular calcium
      and sodium. Fura-2 was used to measure basal and angiotensin II-stimulated
      intracellular free calcium concentration. Effluxed calcium-45 was measured over
      5s intervals to determine basal and angiotensin II-stimulated calcium efflux
      rates in SHR and in WKY rats. RESULTS: No significant difference between SHR and
      WKY rats was observed in basal intracellular free calcium concentration or
      100nmol/l angiotensin II-stimulated peak intracellular free calcium
      concentration. However, significantly elevated basal and 100 nmol/l angiotensin
      II-stimulated calcium-45 efflux rates were found in SHR. The calcium-45 efflux
      rates in SHR were elevated when the efflux was normalized with respect to the
      bulk intracellular free calcium concentration. The time taken to reach the
      maximum calcium-45 efflux rate after angiotensin II stimulation was reduced in
      SHR compared with that in WKY rats and was dose-dependent in both rat strains.
      CONCLUSION: The calcium-pump mediated calcium efflux pathway appears to be more
      efficient in SHR. This may be the result of post-translational modification,
      enhanced calcium pump sites in a critical region of the membrane, or the presence
      of a pool of calcium near the plasma membrane that is not readily detected by
      cytosolic Fura-2 but is higher in SHR both before and after angiotensin II
      stimulation.

PMID- 8761892
TI  - Erythrocyte membrane cholesterol distribution in patients with untreated
      essential hypertension: correlation with sodium-lithium countertransport.
AB  - OBJECTIVE: To determine whether the membrane cholesterol distribution is
      associated with the increased activity of sodium-lithium countertransport in the
      erythrocytes of normocholesterolaemic and hypercholesterolaemic patients with
      untreated essential hypertension. METHODS: Erythrocytes were prepared from venous
      blood samples obtained from normotensive subjects and hypertensive
      (normocholesterolaemic and hypercholesterolaemic) patients. The membrane
      cholesterol distribution between the inner and outer monolayers was measured by
      means of cholesterol oxidation to cholestenone after continuous cholesterol
      oxidase treatment. The sodiumlithium countertransport activity was determined by
      measurements of external sodium (150 mmol/l)-stimulated lithium efflux. The
      statistical analysis was conducted by analysis of variance with Tukey's
      correction and correlations were performed by linear regression analysis using
      Pearson's correlation coefficient. RESULTS: The half-times for cholesterol
      oxidation were significantly higher in patients with untreated essential
      hypertension, either with (25.4 +/- 5.6 min) or without (21.7 +/- 2.9 min)
      concomitant hypercholesterolaemia, than in the controls (15.3 +/- 2.8 min).
      Sodium-lithium counter-transport activities were also higher in the hypertensive
      patients (0.410 +/- 0.094 and 0.304 +/- 0.037 mmol/h per litre cell for the
      hypercholesterolaemic and normocholesterolaemic groups, respectively) than in the
      controls (0.262 +/- 0.081 mmol/h per litre cell). In single-regression analysis,
      the half-time for membrane cholesterol oxidation was positively correlated to the
      erythrocyte cation flux mediated by the sodium-lithium countertransport.
      CONCLUSION: It is hypothesized that the sodium-lithium countertransport activity
      might be influenced by membrane structural cholesterol domains.

PMID- 8761893
TI  - Effects of intracerebroventricular administration of 6-hydroxydopamine on ouabain
      like immunoreactivity in plasma and the hypothalamo-pituitary axis in rats.
AB  - OBJECTIVE: To examine the role of central mechanisms on the production and
      release of an ouabain-like factor, the effects of intracerebroventricular
      injections of 6-hydroxydopamine on the tissue content and on the plasma level of
      the ouabain-like factor were determined in rats. METHODS: The vehicle (0.1%
      ascorbic acid in 0.9% saline) and 6- hydroxydopamine (250 micrograms/rat) were
      injected into the left lateral ventricle in ether-anaesthetized Wistar rats.
      Hypothalamus, pituitary, adrenal and venous blood was sampled 24h and 7 days
      later. The procedure was repeated using another rat group 7 days later.
      Characteristics of immunoreactive ouabain-like factor were determined by a
      combination of high-performance liquid chromatography and a highly sensitive
      enzyme-linked immunosorbent assay for ouabain. The level of the ouabain-like
      factor in these tissues and in plasma extracts measured by the enzyme-linked
      immunosorbent assay was compared between the two groups receiving 6
      hydroxydopamine and the vehicle. RESULTS: Twenty-four hours after the
      intracerebroventricular injections of 6-hydroxydopamine, the ouabain-like factor
      level in the pituitary, hypothalamus and plasma had decreased significantly,
      whereas the ouabain-like factor level in the adrenal had not changed. The content
      of noradrenaline in the hypothalamus was also decreased markedly 7 days later and
      the content of ouabain-like factor in the pituitary remained low. On liquid
      chromatography the elution pattern of the ouabain-like factor in plasma and in
      tissue extracts coincided with that of authentic ouabain. CONCLUSIONS:
      Intracerebroventricular treatments with 6-hydroxydopamine elicited decreases in
      ouabain-like factor contents in the pituitary, the hypothalamus and the plasma.
      These results suggest that the production and release of ouabain-like factor are
      closely associated with the brain, particularly the hypothalamus-pituitary axis,
      and that noradrenergic or dopaminergic neurons, or both, play a key role in this
      mechanism.

PMID- 8761894
TI  - Induction of HELLP syndrome-like biochemical parameters by stimulation of the
      celiac ganglion in rats.
AB  - OBJECTIVE: An animal model of HELLP (hemolysis, elevated liver enzymes, low
      platelets) syndrome was developed by means of stimulation of the celiac ganglion
      in rats. METHODS: The celiac ganglion in pregnant or non-pregnant rats was
      exposed to endotoxin (lipopolysaccharide, LPS) (500 micrograms/50 microliters),
      potassium chloride (0.2 mol/l/50 microliters), or saline solution (50
      microliters). In another group of rats the bifurcation of the abdominal aorta was
      exposed to LPS (500 micrograms/50 microliters). Blood pressure, platelet count,
      hematocrit, serum aspartate transaminase (AST), alanine transaminase (ALT),
      lactate dehydrogenase (LDH), and plasma norepinephrine and epinephrine were
      measured for 6 h after treatment. Histopathologic studies were also performed in
      these rats. RESULTS: A significant increase in blood pressure, AST, ALT, LDH,
      norepinephrine, and epinephrine was found in the endotoxin-treated pregnant rats
      compared with control rats treated with the saline solution. A significant
      decrease in platelet count was found in endotoxin-treated pregnant rats compared
      with the control rats. A significant increase in blood pressure, AST,
      norepinephrine, and epinephrine was found in the potassium chloride-treated
      pregnant rats compared with control rats. Blood pressure and biochemical
      parameters remained unchanged in the pregnant rats treated with LPS at the
      bifurcation of the abdominal aorta, as in those treated with saline at the celiac
      ganglion. Histologic examination of liver tissues treated with LPS or potassium
      chloride showed varying degrees of ischemic necrosis of hepatocytes similar to
      that observed in the human HELLP syndrome. Blood pressure, biochemical
      parameters, and histologic findings in non-pregnant rats were almost the same as
      those in pregnant rats. CONCLUSION: This study suggests that exogenous
      stimulation of the celiac ganglion causes an increase in the blood pressure and
      liver ischemia, resulting in HELLP syndrome-like disease in pregnant and non
      pregnant rats.

PMID- 8761895
TI  - Clearance receptors for atrial natriuretic petide in Milan hypertensive and
      normotensive rats.
AB  - OBJECTIVE: Renal responses of anaesthetized Milan hypertensive (MHS) and Milan
      normotensive (MNS) rats to des-[Glu18-Ser19-Gly20-Leu21-Gly22]r atrial
      natriuretic peptide-4-23 (cANP4-23) a specific ligand for atrial natriuretic
      petide (ANP) clearance receptors were examined. METHODS: The peptide was
      administered intravenously as an initial bolus injection (10 micrograms/kg body
      weight) followed by constant infusion (1 microgram/min per kg body weight) for 30
      min. Glomerular filtration rate, urine flow, sodium excretion and mean blood
      pressures were measured. Using the same protocol, plasma ANP levels were
      determined. RESULTS: Plasma ANP levels were significantly increased in both Milan
      strains (from 9.5 +/- 1.8 to 23.7 +/- 3.2 fmol/ml in MHS rats and from 9.8 +/-
      1.2 to 15.9 +/- 1 fmol/ml in MNS rats). This increase was significantly greater
      in the MHS than in the MNS rats. The cANP4-23 infusions were diuretic and
      natriuretic in both strains of rats but despite a greater rise in plasma ANP
      level, the renal response was attenuated in the MHS compared with that in the MNS
      rats. Furthermore, the time course differed in that the hypertensive rats had a
      diuresis of slower onset. During cANP4-23 infusion, the mean blood pressure
      decrease was greater in the MHS rats, consistent with the fact that phenylephrine
      precontracted isolated MHS rat aortae were threefold more sensitive to ANP
      induced relaxation than were MNS rat aortae. Displacements of [125l]-rANP by rANP
      and cANP4-23 in isolated renal glomeruli indicated that MHS rats have similar
      amounts of cANP receptors but with a higher affinity for cANP than have MNS rats.
      CONCLUSION: cANP4-23 infusion increased plasma ANP more in MHS than in MNS rats.
      Renal responses were attenuated in the MHS rat compared with those in MNS rats.
      These differential actions cannot be explained in terms of glomerular ANP
      receptor densities, although aortic ring sensitivities differ between the two
      strains of rat.

PMID- 8761896
TI  - Major cardiovascular risk factors in Lyon hypertensive rats. A correlation
      analysis in a segregating population.
AB  - OBJECTIVE: To investigate the association of blood pressure with the other major
      cardiovascular risk factors in a large population of back-cross to Lyon
      hypertensive (LH) rats. METHODS: Mean arterial pressure was recorded in male
      freely moving Lyon normotensive (LN), LH, F1 and backcross to LH rats aged 30
      weeks. Plasma cholesterol, triglycerides, insulin, creatinine, urea, fibrinogen
      and haematocrit levels, and the insulin: glucose ratio were measured in 31-week
      old rats and 24h albuminuria in 6-week-old rats. RESULTS: Adult LH rats exhibited
      a significant increase in plasma lipids, insulin, fibrinogen, creatinine, urea
      and haematocrit levels compared with LN rats. In young LH rats, at an age at
      which blood pressure is slightly increased, albuminuria was increased to a
      greater extent than expected from their blood pressure levels. In the adult back
      cross to LH rats, only the plasma cholesterol level was associated with blood
      pressure. Moreover, the plasma cholesterol level was related to fibrinogen and
      haematocrit levels. Finally, in the same rats, albuminuria developed early in
      life was positively related to hypercholinesterolaemia measured later in life.
      CONCLUSION: Plasma cholesterol, fibrinogen, haematocrit levels and early
      albuminuria could act synergistically in the enhancement or the development, or
      both, of vascular and kidney damage in the LH rat. Most interestingly, the
      association between plasma cholesterol level and blood pressure indicates that,
      as in essential hypertension, hypercholesterolaemia is a major phenotype
      associated with hypertension in the LH rat.

PMID- 8761897
TI  - Effects of infusion of combinations of adrenocorticosteroids on systemic and
      regional haemodynamics in conscious sheep.
AB  - OBJECTIVE: To compare the cardiovascular, metabolic and endocrine responses to
      infusions of two combinations of adrenocorticosteroids and to determine their
      contribution to the haemodynamic effects of corticotrophin. METHODS: The effect
      of 5 day's infusion of combinations of seven corticosteroids (aldosterone,
      cortisol, corticosterone, 11-deoxycorticosterone, 11-deoxycortisol, 17 alpha
      hydroxyprogesterone and 17 alpha-hydroxy-20 alpha-dihydroprogesterone and five
      corticosteroids (17 alpha-hydroxyprogesterone and 17 alpha,20 alpha
      hydroxyprogesterone omitted) on arterial pressure, cardiac output (measured using
      electromagnetic flow probes) and regional blood flows (measured using transit
      time flow probes) was determined in conscious sheep. RESULTS: Combined infusion
      of seven steroids increased mean arterial pressure from 79 +/- 2 to 91 +/- 2 mmHg
      (day 5). Cardiac output increased from 5.42 +/- 0.22 to 6.55 +/- 0.41 l/min owing
      to an increase in stroke volume. Mesenteric conductance fell from 6.3 +/- 0.4 to
      5.4 +/- 0.5 ml/min per mmHg, and renal conductance increased from 3.1 +/- 0.1 to
      4.0 +/- 0.1 ml/min per mmHg, resulting in no change in total peripheral
      conductance. There were only minor effects on the coronary and iliac vascular
      beds. Infusion of five steroids caused similar changes in mean arterial pressure
      (from 78 +/- 1 to 89 +/- 2 mmHg on day 5), cardiac output and regional blood
      flows. The cardiovascular, fluid, electrolyte and endocrine responses to both
      steroid treatments were similar to those with corticotrophin. CONCLUSIONS:
      Infusion of combinations of seven or five adrenocortical steroids reproduced the
      cardiovascular actions of corticotrophin, namely increases in arterial pressure,
      and cardiac output, mesenteric vasoconstriction and renal vasodilation. This
      contrasts with previous studies in which only an infusion of steroids including
      17 alpha-hydroxyprogesterone and 17 alpha,20 alpha-OHP reproduced the pressor
      effect of corticotrophin fully, possibly because in these sheep, as has been
      proposed to be the case in humans, the dose-response curves for the
      hypertensinogenic, mineralocorticoid and glucocorticoid actions overlap.

PMID- 8761898
TI  - Hyperinsulinaemia as a predictor of hypertension: an 11-year follow-up study in
      Japan.
AB  - OBJECTIVE: To examine the hypothesis that hyperinsulinaemia is associated with
      the development of borderline hypertension or hypertension. DESIGN: Blood
      pressure status in non-obese normotensives (< 140/90 mmHg, n = 135) people were
      re-examined after 11 years after the baseline examination. Participants were
      selected from a 1981 population-based health examination and had a high blood
      glucose level or more than a trace of glucose in their urine. Out of 319 people
      recruited for further examination of glucose tolerance status, 135 normotensive
      participants with body mass index < 26 kg/m2 and without diabetes according to
      World Health Organization criteria were re-examined at the follow-up survey.
      RESULTS: Sixty-two (46%) out of 135 normotensive participants were hypertensive
      (defined as blood pressure > or = 140/90 mmHg) or receiving antihypertensive
      medication (n = 8) at the follow-up survey. Significant associations between the
      development of hypertension and baseline parameters were observed for systolic
      and diastolic blood pressure, serum triglycerides, high-density lipoprotein (HDL)
      cholesterol, fasting and 60 min post-load insulin levels, and the sum of insulin
      concentrations from fasting to 180 min after glucose challenge after adjustments
      for age and sex. Odds ratios (95% confidence intervals) for the future
      development of hypertension between the highest and the lowest tertiles of
      insulin levels were 4.06 (1.40-11.76) for fasting insulin, 4.25 (1.45-12.45) for
      60 min post-glucose load insulin, and 3.88 (1.34-11.20) for the sum of insulin
      concentrations, after adjustment for age, sex, systolic blood pressure, body mass
      index and alcohol consumption. Further adjustments for serum triglycerides and
      serum creatinine did not affect the insulin-hypertension relationship.
      CONCLUSION: The present study suggests that hyperinsulinemia is significantly
      related to the development of hypertension in non-obese and non-diabetic Japanese
      people.

PMID- 8761899
TI  - Differential effect of chronic treatment with two beta-blocking agents on insulin
      sensitivity: the carvedilol-metoprolol study.
AB  - BACKGROUND: Hypertensive patients frequently show resistance to insulin
      stimulated glucose uptake and hyperinsulinemia. Diuretics and beta-adrenoceptor
      blocking agents have been found to decrease insulin sensitivity, whereas alpha 1
      blockers and angiotensin converting enzyme inhibitors seem to improve it.
      OBJECTIVE: To compare the effects of a 3 months' antihypertensive treatment with
      carvedilol, a non-selective beta-adrenoceptor blocker with alpha 1-blocking
      properties, with the beta 1-selective receptor blocker metoprolol on insulin
      sensitivity in non-diabetic hypertensive patients. DESIGN: A multicenter double
      blind randomized study. SUBJECTS AND METHODS: Seventy-two non-diabetic
      hypertensive patients were randomly assigned to treatment with either carvedilol
      or metoprolol. An isoglycemic, hyperinsulinemic glucose clamp was conducted
      before and after 12 weeks of treatment; the metabolic clearance rate for glucose
      was taken as an indicator of insulin sensitivity. RESULTS: The two groups did not
      differ in age, sex, body mass index, blood pressure or lipids, and treatment
      effectively lowered blood pressure. In both groups, insulin sensitivity was
      impaired at baseline. After metoprolol treatment, insulin sensitivity further
      decreased significantly by about 14%, whereas it increased after carvedilol.
      There was also a decrease in high-density lipoprotein and an increase in
      triglycerides levels in patients in the metoprolol-treated group, whereas these
      parameters remained unchanged in patients in the carvedilol-treated group.
      CONCLUSION: This study confirms previous findings of a reduction in insulin
      sensitivity after chronic metoprolol treatment. Carvedilol treatment, however,
      resulted in a small amelioration of insulin resistance and a better lipid profile
      [corrected]. We thus demonstrate that a beta-blocker with alpha 1-blocking
      properties has favorable effects on glucose metabolism, suggesting a potentially
      important role of peripheral blood flow in regulating glucose uptake. These
      findings imply that beta-blocker treatment, when combined with alpha 1-blocking
      activity has advantageous effects on insulin sensitivity and lipids and could
      therefore be suitable for patients with the metabolic syndrome.

PMID- 8761900
TI  - A comparative study of hypertension prevalence, awareness, treatment and control
      rates in St Lucia, Jamaica and Barbados.
AB  - BACKGROUND: Cardiovascular diseases represent the most common cause of death in
      the English-speaking Caribbean, and hypertension represents the most important
      predisposing condition. However, direct between-country comparative studies in
      the Caribbean have not previously been undertaken. OBJECTIVE: To obtain estimates
      of hypertension prevalence, awareness, treatment and control in three countries
      in the Caribbean. DESIGN: Population-based samples of adults aged 25-74 years in
      St Lucia, Barbados and Jamaica were surveyed regarding their cardiovascular
      health and their blood pressures were measured using a highly standardized
      protocol. A reference site was available from a collaborative study among blacks
      in metropolitan Chicago, Illinois, USA. RESULTS: At the 160/95 mmHg threshold,
      age-adjusted hypertension prevalence estimates for Jamaica, St Lucia and Barbados
      were 17.5, 18.3 and 21.5%, respectively, and 24.7, 26.9 and 27.9%, respectively,
      at the 140/90 mmHg threshold. The corresponding estimate for the Chicago site at
      the 140/90 mmHg threshold was 33.2%. The gradient in prevalence resembled the
      gradient in body mass index (25.7 kg/m2 in Jamaica to 29.3 kg/m2 in the USA). At
      the 160/95 mmHg threshold, the proportion of all hypertensives who were aware of
      their disease, pharmacologically treated and controlled was highest in Barbados
      (90, 85 and 72%, respectively) and lowest in St Lucia (74, 59 and 35%,
      respectively). Men, particularly those aged less than 55 years, were less likely
      to have their hypertension treated and controlled. CONCLUSIONS: Compared with
      estimates from earlier independent surveys, considerable progress has been made
      in hypertension detection and control in these countries, which should lead to
      sizable reductions in the burden of cardiovascular disease.

PMID- 8761901
TI  - Vitamin C status and blood pressure.
AB  - OBJECTIVE: To examine the cross-sectional relationship between blood pressure and
      plasma vitamin C. DESIGN: A cross-sectional analysis. SETTING: A population-based
      study. SUBJECTS: The subjects were 835 men and 1025 women aged 45-75 years
      registered with general practices in Norfolk. INTERVENTIONS: Completion of health
      and lifestyle questionnaire and attendance for a health check. MAIN OUTCOME
      MEASURES: Diastolic blood pressure (DBP), systolic blood pressure (SBP) and
      plasma vitamin C level. RESULTS: The mean SBP was 135.8 +/- 18.5 mmHg (mean +/-
      SD) and the mean DBP was 82.5 +/- 11.3 mmHg. The mean plasma vitamin C level was
      52.6 +/- 19.7 mumol/l. The plasma vitamin C level was negatively correlated both
      with SBP and with DBP. These correlations persisted after adjustment for age, sex
      and body mass index. Adjusting for other confounders including cigarette smoking,
      physical activity and alcohol intake did not alter the observed association.
      Exclusion of subjects taking vitamin supplements and those with known
      hypertension did not affect the results. The differences in SBP and in DBP for a
      50 mumol/l difference in vitamin C, estimated using linear regression, were -3.6
      and -2.6 mmHg, respectively. CONCLUSIONS: The plasma vitamin C level may be a
      marker of other factors; nevertheless, these results are consistent with other
      published work indicating that a high intake of vitamin C from food confers
      protection against raised blood pressure and strokes.

PMID- 8761902
TI  - Factors associated with the development of stable hypertension in young
      borderline hypertensives.
AB  - OBJECTIVES: To identify factors predisposing subjects to the development of
      stable hypertension and to estimate their relative importance in 70 young
      patients with borderline hypertension monitored for 10 years. DESIGN:
      Longitudinal evaluation of the incidence of stable hypertension [diastolic blood
      pressure (DBP) > 95 mmHg]. METHODS: Patients were examined at baseline by
      determination of resting blood pressure, intracellular sodium level and
      individual pressor response to mental arithmetic and to intravenous saline
      loading. They were re-examined after 10 years to assess the prevalence of
      established hypertension and the importance of some prognostic variables
      identified prospectively (age, sex, intracellular sodium level, baseline blood
      pressure, pressor response to stress and acute salt-sensitivity). RESULTS: The
      prevalence of sustained hypertension (DBP > 95 mmHg) was 35.8% after 10 years of
      follow-up study. Subjects developing hypertension were older (26.9 +/- 1.3 versus
      21.0 +/- 1.8 years) and showed a higher percentage of family history of
      hypertension (92 versus 64%) and of acute salt-sensitivity (72 versus 53%). The
      pressor response to mental arithmetic was greater in patients who developed
      hypertension (systolic blood pressure 26.9 +/- 1 versus 22.7 +/- 0.9 mmHg, P =
      0.005 DBP = 16.6 +/- 0.8 versus 13.1 +/- 0.7 mmHg, P = 0.005), who also showed
      higher levels of intracellular sodium (30.7 +/- 0.6 versus 27.3 +/- 0.5 mmol/kg,
      P = 0.001). The same variables were found to be related to the development of
      hypertension in a multivariate analysis and the concomitant presence of 4-5 risk
      factors was associated with a reasonable predictive power for the identification
      of patients at high risk (sensitivity 72%, specificity 67%, predictive accuracy
      76%). CONCLUSIONS: The present study demonstrates that borderline hypertensives
      at high risk of stable hypertension can be identified by the concomitant
      evaluation of some clinical and cellular characteristics directly related to long
      term development of high blood pressure.

PMID- 8761903
TI  - Non-invasive screening for renal artery stenosis with ultrasound contrast
      enhancement.
AB  - OBJECTIVE: Our aim was to evaluate duplex ultrasound imaging in the
      identification of renal artery stenosis using a new technique to enhance the
      recorded Doppler signal. DESIGN: Colour Doppler studies of interlobar renal
      arteries were performed before and after enhancement using an intravenous
      contrast of galactose microparticle suspension containing microbubbles (Levovist,
      Schering) in patients with angiographically confirmed renal artery stenosis.
      SETTING: Blood Pressure Unit, St. George's Hospital Medical School, and
      Department of Radiology. The Middlesex Hospital, London, UK. PARTICIPANTS: Twenty
      one consecutive hypertensive patients in whom the diagnosis of renal artery
      stenosis was made on digital subtraction angiography. MAIN OUTCOME MEASURES: The
      diagnosis of haemodynamically significant renal artery stenosis (> or = 60% on
      angiography). RESULTS: With Levovist, there was a 20 db increase in the Doppler
      intensity and, as a result, intrarenal signals were much more clearly delineated
      and distinct spectral waveforms were obtained from all but one kidney, which was
      occluded. Significant associations were found between the degree of stenosis (as
      assessed by angiography) and the following Doppler parameters: diastolic velocity
      (F = 7.6; P < 0.01), acceleration time (F = 33.5, < 0.0001), peak systolic
      velocity (F = 37.7, P < 0.0001) and acceleration (F = 60.0; P < 0.0001). Without
      enhancement, there were five false-positive and two false-negative examinations
      (sensitivity 85%; specificity 79%) using the acceleration cut-off value of 3.5
      m/s2 to identify haemodynamically significant renal artery stenosis (> or = 60%
      on angiography). After contrast enhancement, there were only three false-positive
      and one false-negative examinations (sensitivity 94% and specificity of 88%)
      using the acceleration cut-off value of 3.75 m/s2 and the examination time was
      reduced by approximately half (sensitivity and specificity of 90% using the
      acceleration cut-off value of 3.5 m/s2). CONCLUSIONS: Our results suggest that
      renal duplex scanning using contrast enhancement is a promising new non-invasive
      technique in screening patients with suspected renal artery stenosis. Contrast
      enhancement produces more reproducible spectral waveforms, improves accuracy and
      halves the examination time.

PMID- 8761904
TI  - A prospective study of helical computed tomography angiography versus angiography
      for the detection of renal artery stenoses in hypertensive patients.
AB  - OBJECTIVE: To compare helical computed tomography angiography with arterial
      digital subtraction angiography in the diagnosis of renal artery stenoses.
      METHODS: Fifty hypertensives (24 men; mean age 53 years) were prospectively
      studied with computed tomography (Somaton Plus S, Siemens) and digital
      angiography (double-blind evaluation). Computed tomography was performed both in
      the sequential (the length of the abdomen) and in the helical (6 cm around renal
      arteries) modes during injection of 120 cm3 contrast medium. RESULTS: Digital
      angiography visualized 16 significant (< 50% on quantitative angiography)
      stenoses (16/131 renal arteries, including 32 accessory), in 14 (28%) patients.
      On helical computed tomography, 16 stenoses were detected, in 49 patients (16/122
      renal arteries, seven accessory arteries were not identified because they were
      located out side the scan area); two patients had false-positive helical computed
      tomography results. The computed tomography sensitivity, specificity, positive
      and negative predictive values were 87.5% (14/16), 98.2% (111/114), 87.5% and
      98.2%, respectively. In the sequential mode, two cases of bilateral adrenal
      hyperplasia, two aortic aneurysms and one renal neoplasm were detected. None of
      these patients had renal artery stenosis. CONCLUSIONS: Helical computed
      tomography is a suitable new non-invasive diagnostic modality for the detection
      of renal artery stenosis or adrenal pathology. With continued development and
      evaluation computed tomography could prove useful as a screening tool or as a
      replacement for digital angiography in patients with possible secondary
      hypertension.

PMID- 8761905
TI  - Nisoldipine and pressure-natriuresis curves in transgenic (mRen2)27 rats.
AB  - OBJECTIVES: The mechanism by which antihypertensive drugs influence pressure
      natriuresis gives insight into their mode of action. We tested the effects of
      nisoldipine on pressure natriuresis, glomerular filtration rate, and renal blood
      flow in transgenic (mRen2)27 rats and Sprague-Dawley Hannover control rats.
      METHODS: The rats were anaesthetized, uninephrectomized with denervation of the
      remaining kidney, administered noradrenaline, 17-hydroxycorticosterone,
      vasopressin, and aldosterone to 'clamp' these regulatory systems and nisoldipine
      (0.5 mg/kg bolus plus 0.017 mg/kg per min). The glomerular filtration rate and
      renal plasma flow were measured with inulin and PAH. Renal perfusion pressure was
      varied from approximately 100 to approximately 200 mmHg with clamps above and
      below the kidney. RESULTS: Nisoldipine shifted not only the pressure-diuresis and
      pressure-natriuresis curves but also the fractional sodium and water curves
      leftwards in transgenic (mRen2)27 rats, but not in Sprague-Dawley Hannover rats.
      Nisoldipine increased the glomerular filtration rate and renal blood flow in
      transgenic (mRen2)27 rats but not in Sprague-Dawley Hannover rats. CONCLUSIONS:
      Nisoldipine shifts the pressure-natriuresis curve in transgenic (mRen2)27 rats
      leftwards; sodium and water excretion is increased for any given perfusion
      pressure. This effect is intrinsic to the kidney and is associated with
      inhibition of tubular sodium and water reabsorption and with an increase in renal
      perfusion.

PMID- 8761923
TI  - Selective distribution of the NMDA-R1 glutamate receptor in astrocytes and
      presynaptic axon terminals in the nucleus locus coeruleus of the rat brain: an
      immunoelectron microscopic study.
AB  - The regional and cellular distribution of the different classes of excitatory
      amino acid receptors with respect to the noradrenergic neurons of the nucleus
      locus coeruleus (LC) are unknown. We therefore combined immunoperoxidase labeling
      for the R1 subunit of the N-methy-D-aspartate (NMDA) receptor with immunogold
      silver localization of the catecholamine synthesizing enzyme, tyrosine
      hydroxylase (TH), in single sections through the rat LC to determine the
      subcellular localization of this glutamate receptor subtype with respect to the
      noradrenergic neurons. At the light microscopic level, there was light to
      moderate labeling for the NMDA-R1-like (li) receptor in the caudal pole of the LC
      and dense labeling in the dorsolateral aspect of the LC adjacent to the superior
      cerebellar peduncle. In the rostral pole of the LC which is enriched with
      noradrenergic dendrites, significant overlap between both immunoreactivities
      could be observed. At the ultrastructural level, immunoperoxidase labeling for
      NMDA-R1 was selectively distributed in astrocytic processes and within
      presynaptic axon terminals but was rarely seen in catecholamine-containing somata
      or dendrites. Peroxidase labeling for NMDA-R1, however, was occasionally observed
      in dendrites in the rostral pole of the LC. Most of these dendrites lacked
      detectable levels of TH, although TH immunoreactivity was apparent in the
      neuropil. Dendrites containing NMDA-R1-li immunoreactivity often received
      asymmetric (excitatory-type) contacts from unlabeled terminals. NMDA-R1-li
      immunoreactive axon terminals usually contained small clear, as well as large
      dense-core vesicles and were often apposed to unlabeled dendrites, axon terminals
      and/or glial processes. These results provide the first ultrastructural evidence
      that NMDA-R1-li immunoreactivity is selectively distributed within astrocytic
      processes and presynaptic axon terminals within the LC.

PMID- 8761924
TI  - gamma-Aminobutyric acid and glycine in the baboon cochlear nuclei: an
      immunocytochemical colocalization study with reference to interspecies
      differences in inhibitory systems.
AB  - Previous studies of the cochlear nuclei in cat, rat, and guinea pig have
      demonstrated neural structures that are enriched in the inhibitory
      neurotransmitter amino acids gamma-aminobutyric acid (GABA) and glycine. In these
      mammals, inhibitory terminals are widely distributed throughout the nuclear
      complex, but somata of inhibitory neurons are concentrated in the dorsal cochlear
      nucleus, in granule cell regions, and in the cap area. Because these are the
      subdivisions that undergo the most pronounced phylogenetic changes in primates,
      we wanted to see whether the inhibitory systems are influenced by changes in
      cytoarchitecture. Therefore, we applied light microscopic postembedding
      immunostaining and optical densitometry to the cochlear nuclei of an anthropoid
      primate, the Senegalese baboon (Papio anubis). Our results demonstrate that, in
      baboon 1) glycinergic neurons and axons in the ventral cochlear nucleus seem to
      form a commissural system similar to that of other mammals; 2) the
      tuberculoventral system appears to be unchanged in morphology but exhibits a
      higher level of colocalization of GABA with glycine; 3) there is a reduction of
      the granule/cartwheel cell system, which is reflected in lesser numbers of
      inhibitory cartwheel, Golgi, and molecular layer stellate cells; 4) the cap area
      is larger than in rodents and carnivores and contains many neurons that
      colocalize GABA and glycine; and 5) throughout the nuclear complex, a higher
      proportion of the inhibitory terminals colocalize GABA and glycine. We conclude
      that modulation of the ascending auditory pathway in baboon is likely to differ
      from that in rodents and cat.

PMID- 8761925
TI  - Dendritic morphology of projection neurons in the cat pretectum.
AB  - The distribution and dendritic morphology of neurons in the cat pretectal nuclear
      complex were analyzed with respect to their projection to the ipsilateral dorsal
      lateral geniculate nucleus (LGNd) and the ipsilateral inferior olive (IO). Single
      and double retrograde tracing techniques were combined with intracellular
      injections of either horseradish peroxidase into electrophysiologically
      identified pretectal neurons or Lucifer Yellow into retrogradely labeled somata.
      Pretectal cells afferent to the LGNd were located in the nucleus of the optic
      tract (NOT), adjacent dorsal terminal nucleus of the accessory optic system
      (DTN), and posterior pretectal nucleus (NPP). Cells projecting to the IO were
      also distributed throughout the NOT-DTN and dorsal part of the NPP. Separate
      tracer injections (fluorogold and horseradish peroxidase [HRP] or granular blue)
      into the LGNd and the IO showed considerable overlap of labeled neurons in the
      NOT and dorsal NPP. Double-labeled neurons, however, were not observed after
      double tracer injections into LGNd and IO. Partial topographical segregation of
      the two populations was observed along the dorsoventral axis because LGNd
      projecting neurons exhibited maximum density ventral to that of IO neurons.
      Pretectal cells to the LGNd had cell body diameters between 16 and 48 microns.
      Somatic shapes varied between fusiform and multipolar with considerable overlap
      between these two morphological appearances. Neurons projecting to the IO
      exhibited similar cell body sizes and their morphology also varied from fusiform
      to multipolar. Quantitative analysis of dendritic field size and orientation,
      number and order of dendritic arborizations, and symmetry of the dendritic tree
      revealed no statistically significant difference between the two neuronal
      populations. Hence, neurons of the two populations cannot be unequivocally
      identified just from the dendritic morphology. By contrast, dendritic morphology
      was correlated with the topographical location of either cell type within the
      pretectal nuclei rather than projection. Thus, the morphological appearance of
      neurons located dorsally predominantly was fusiform while neurons located
      ventrally mostly were multipolar.

PMID- 8761926
TI  - Monosynaptic input from cutaneous sensory afferents to fin motoneurons in
      lamprey.
AB  - The sensory control of lamprey dorsal fin motoneurons was studied by using paired
      intracellular recordings combined with a morphological analysis. Dorsal cells
      innervating the skin of the dorsal fin and fin motoneurons were retrogradely
      labeled by injecting fluoresceincoupled dextran amines into the dorsal fin.
      Labeled motoneurons and dorsal cells showed close appositions, suggesting that
      the dorsal cells innervating the fin region make monosynaptic connections with
      fin motoneurons. By using conventional electrophysiological criteria,
      monosynaptic excitatory connections were found between fin dorsal cells and fin
      motoneurons. In addition, Lucifer yellow injection followed by confocal three
      dimensional (3-D) reconstructions of monosynaptically connected pairs, revealed
      close apposition between dorsal cell axons and the distal dendrites of fin
      motoneurons. Each fin motoneuron received monosynaptic excitatory input from at
      least four different afferents. The amplitude of the monosynaptic excitatory
      postsynaptic potential (EPSP)s was reduced by administration of the N-methyl-D
      aspartate (NMDA) receptor antagonist DL,2 amino-5-phosphovaleric acid (APV).
      Sensory stimulation could also elicit di- or oligosynaptic inhibitory
      postsynaptic potential (IPSP)s, which were blocked by the glycine antagonist
      strychnine, resulting in the appearance of large monosynaptic EPSPs, which could
      induce action potentials.

PMID- 8761927
TI  - Ciliary neurotrophic factor stimulates the expression of glial fibrillary acidic
      protein by brain astrocytes in vivo.
AB  - Ciliary neurotrophic factor is a cytokine that has effects on neuronal survival
      and phenotype in vitro and in vivo. Ciliary neurotrophic factor has also been
      shown to have effects on microglia and oligodendrocytes in vitro and in vivo. In
      this study, we demonstrate in vivo effects of ciliary neurotrophic factor on
      astrocytes in both the injured and uninjured central nervous system. Ciliary
      neurotrophic factor increases the expression of glial fibrillary acidic protein
      and induces concomitant morphological changes in central nervous system
      astrocytes. Messenger RNA for both ciliary neurotrophic factor and the alpha
      component of the ciliary neurotrophic factor receptor is demonstrated in the
      optic nerve, an essentially pure population of central nervous system glia. We
      also report here that the promoter region of the glial fibrillary acidic protein
      gene contains sequences thought to confer direct ciliary neurotrophic factor
      modulation of glial fibrillary acidic protein gene transcription. Although it is
      thought that astrocytes are a source of endogenous ciliary neurotrophic factor in
      the central nervous system and that neurons express the alpha-component of the
      ciliary neurotrophic factor receptor, the results of the present investigation
      suggest that astrocytes themselves respond to ciliary neurotrophic factor and
      that ciliary neurotrophic factor may also be important in glial cell-cell
      interactions.

PMID- 8761928
TI  - Distribution of bombesin-like immunoreactivity in the nucleus of the solitary
      tract and dorsal motor nucleus of the rat and human: colocalization with tyrosine
      hydroxylase.
AB  - Bombesin is a peptide neurotransmitter/neuromodulator with important autonomic
      and behavioral effects that are mediated, at least in part, by bombesin
      containing neurons and nerve terminals in the nucleus of the solitary tract (NTS)
      and the dorsal motor nucleus of the vagus (DMV). The distribution of bombesin
      like immunoreactive nerve terminals/fibers and cell bodies in relation to a
      viscerotopically relevant subnuclear map of this region was studied by using an
      immunoperoxidase technique. In the rat, bombesin fiber/terminal staining was
      heavy in an area that included the medial subnucleus of the NTS and the DMV over
      their full rostral-caudal extent. Distinctly void of staining were the
      gelatinous, central, and rostral commissural subnuclei and the periventricular
      area of the NTS, regions to which gastric, esophageal, cecal, and colonic primary
      afferents preferentially project. The caudal commissural and dorsal subnuclei had
      light bombesin fiber/terminal staining, as did the intermediate, interstitial,
      ventral, and ventrolateral subnuclei. With colchicine pretreatment, numerous cell
      bodies were stained in the medial and dorsal subnuclei, with fewer neurons in the
      caudal commissural, intermediate, interstitial, ventral, and ventrolateral
      subnuclei. Bombesin-like immunoreactive neurons were found in numerous other
      areas of the brain, including the ventrolateral medulla, the parabrachial
      nucleus, and the medial geniculate body. In the human NTS/DMV complex, the
      distribution of bombesin fiber/terminal staining was very similar to the rat. In
      addition, occasional bombesin-like immunoreactive neurons were labeled in a
      number of subnuclei, with clusters of neurons labeled in the dorsal and
      ventrolateral subnuclei. Double immunofluorescence studies in rat demonstrated
      that bombesin colocalizes with tyrosine hydroxylase in neurons in the dorsal
      subnucleus of the NTS. Bombesin does not colocalize with tyrosine hydroxylase in
      any other location in the brain. In conclusion, the distribution of bombesin in
      the NTS adheres to a viscerotopically relevant map. This is the anatomical
      substrate for the effects of bombesin on gastrointestinal function and satiety
      and its likely role in concluding a meal. The anatomic similarities between human
      and rat suggest that bombesin has similar functions in the visceral neuraxis of
      these two species. Bombesin coexists with catecholamines in neurons in the dorsal
      subnucleus, which likely mediate, in part, the cardiovascular effects of
      bombesin.

PMID- 8761929
TI  - Differential glutamatergic innervation in cytochrome oxidase-rich and -poor
      regions of the macaque striate cortex: quantitative EM analysis of neurons and
      neuropil.
AB  - One of the hallmarks of the primate striate cortex is the presence of cytochrome
      oxidase (CO)-rich puffs and CO-poor interpuffs in its supragranular layers.
      However, the neurochemical basis for their differences in metabolic activity and
      physiological properties is not well understood. The goals of the present study
      were to determine whether CO levels in postsynaptic neuronal compartments were
      correlated with the proportion of excitatory glutamate-immunoreactive (Glu-IR)
      synapses they received and if Glu-IR terminals and synapses in puffs differed
      from those in interpuffs. By combining CO histochemistry and postembedding Glu
      immunocytochemistry on the same ultrathin sections, the simultaneous distribution
      of the two markers in individual neuronal profiles was quantitatively analyzed.
      As a comparison, adjacent sections were identically processed for the double
      labeling of CO and GABA, an inhibitory neurotransmitter. In both puffs and
      interpuffs, most axon terminals forming asymmetric synapses (84%)--but not
      symmetric ones, which were GABA-IR--were intensely immunoreactive for Glu. GABA
      IR neurons received mainly Glu-IR synapses on their cell bodies, and they had
      three times as many mitochondria darkly reactive for CO than Glu-rich neurons,
      which received only GABA-IR axosomatic synapses. In puffs, GABA-IR neurons
      received a significantly higher ratio of Glu-IR to GABA-IR axosomatic synapses
      and contained about twice as many darkly CO-reactive mitochondria than those in
      interpuffs. There were significantly more Glu-IR synapses and a higher ratio of
      Glu- to GABA-IR synapses in the neuropil of puffs than of interpuffs. Moreover,
      Glu-IR axon terminals in puffs contained approximately three times more darkly CO
      reactive mitochondria than those in interpuffs, suggesting that the former may be
      synaptically more active. Thus, the present results are consistent with our
      hypothesis that the levels of oxidative metabolism in postsynaptic neurons and
      neuropil are positively correlated with the proportion of excitatory synapses
      they receive. Our findings also suggest that excitatory synaptic activity may be
      more prominent in puffs than in interpuffs, and that the neurochemical and
      synaptic differences may constitute one of the bases for physiological and
      functional diversities between the two regions.

PMID- 8761930
TI  - TRK and p75 neurotrophin receptor systems in the developing human brain.
AB  - The prenatal development of the neurons immunoreactive for high-affinity
      tropomycin-related kinase (trk) receptor (pan trk which recognizes trkA, trkB,
      and trkC) and low-affinity p75 neurotrophin receptor (p75NTR) was examined in the
      human brain from embryonic weeks 10 to 34 of gestation. In the embryonic week 10
      specimen in which only brainstem regions were available for evaluation, trk
      immunoreactivity (trk-ir) was observed in the ventral cochlear, solitary, raphe,
      spinal trigeminal, and hypoglossal nuclei, as well as the vestibular complex and
      medullary reticular formation. At this time point of gestation, p75ntr
      immunoreactive (p75NTR-ir) staining was observed within these same regions plus
      the inferior olivary and ambiguus nuclei. At embryonic week 14, trk-ir neurons
      were seen within the subplate zone of the entorhinal cortex, basal forebrain,
      caudate nucleus, putamen, external segment of the globus pallidus, specific
      thalamic nuclei, lateral mammillary nucleus, habenula nucleus, select brainstem
      nuclei, and the dentate nucleus of cerebellum. At this gestational time point,
      p75NTR-ir neurons were observed in each of these structures, with the exception
      of the caudate nucleus, specific thalamic nuclei, lateral mammillary nucleus, and
      habenula nucleus. Additionally, p75NTR-ir neurons were observed within the corpus
      callosum. The staining pattern for both trk and p75NTR remained unchanged at
      embryonic weeks 15 to 16 except for the addition of trk-ir and p75NTR-ir within
      the cortical subplate zone, hippocampus, and subthalamic nucleus. By embryonic
      week 18, trk-ir neurons were widely expressed within mostly all thalamic nuclei.
      In contrast, trk-ir was no longer seen within the hypoglossal, cuneate, and
      gracile nuclei at this time point. This staining pattern for trk and p75NTR
      remained virtually unchanged from embryonic weeks 19 to 20 and embryonic weeks 16
      to 20, respectively. From embryonic weeks 22 to 34, the distribution of both trk
      ir and p75NTR-ir neurons changed gradually. During this period, neurons in most
      thalamic and some brainstem nuclei became progressively immunonegative for trk,
      whereas neurons in the neocortical subplate zone, corpus callosum, and hilar
      region of dentate gyrus gradually lost immunoreactivity for p75NTR. These data
      demonstrate an important and complex role for both the high-(trk) and low- (p75)
      affinity neurotrophin receptors during the development of multiple neuronal
      systems in the human brain.

PMID- 8761932
TI  - A temperature-compensated ultradian clock of Tetrahymena: oscillations in
      respiratory activity and cell division.
AB  - Both a circadian clock and an ultradian clock (period 4-5 h) have previously been
      described for the ciliated protozoon Tetrahymena. The present communication
      demonstrates the existence of yet another cellular clock: an ultradian rhythm
      with a period of about 30 min. The period was found to be well temperature
      compensated over the range studied, i.e., between 19 degrees C and 33 degrees C.
      Ultradian rhythmicity was initiated by dilution of stationary-phase cultures,
      which were kept previously in a light-dark cycle, into fresh medium. LD treatment
      during stationary phase was an absolute requirement, since cultures kept in
      either LL or DD did not produce the ultradian rhythmicity after refeeding. The
      clock exerts control over respiration; the observed oscillation in oxygen uptake
      is just a hand of the clock: after a limitation of oxygen supply had ended, the
      rhythm resumed with the same phase and period as that in control cultures. The
      clock exerts temporal control also over cell division; in the refed culture cell
      division resumed with an oscillation in the number of dividing organisms. The
      period of this oscillation corresponded to that of the rhythm in respiratory
      activity, indicating that the same ultradian clock may exert control over
      different cellular functions. Analysis of a second Tetrahymena strain indicates
      that period length of the ultradian clock is a strain-specific characteristic.

PMID- 8761933
TI  - Circadian locomotor activity rhythm during ontogeny in crayfish Procambarus
      clarkii.
AB  - The characteristics of the circadian rhythm of locomotor activity in the crayfish
      Procambarus clarkii during ontogeny under constant darkness and light-dark (LD
      12:12) conditions were studied in 132 juvenile crayfish, aged 10-140 days,
      divided in four groups. All animals were individually monitored with a motor
      activity recording system. Activity was quantitatively and qualitatively
      analyzed. All ages showed a circadian rhythm, although the probability of its
      appearance increased with age. Period values oscillated between 25.0 h in group I
      (2-4-week-old animals) and 24.3 h in group IV (16-20-week-old animals with more
      than 6 molts), but always with a high standard deviation. Groups II (5-10-week
      old animals) and IV showed a statistically significant bimodal nonrandom
      synchrony of phases. The activity/ rest relationship diminishes as development
      progresses and is most uniform in group IV. We discuss the possibility that the
      pacemaker system responsible for this rhythm might be present from the moment of
      eclosion, but the coupling strength of this system with the effectors might
      change along development. The results presented in this work seem to indicate
      that the central pacemakers responsible for the activity and the ERG rhythm are
      not the same.

PMID- 8761934
TI  - The difference between activity when in bed and out of bed. I. Healthy subjects
      and selected patients.
AB  - The activity records of five groups of healthy or ill subjects have been measured
      for 4-26 days by an accelerometer placed on the nondominant wrist. These data,
      together with a record of times retiring to/rising from bed, have been used to
      produce a series of dichotomy indices for comparing the amounts of activity when
      in bed and out of bed. Reliable differences between individuals were found, with
      healthy subjects showing a greater degree of dichotomy than one subject with
      delayed sleep phase syndrome or three subjects with colorectal cancer. The method
      is convenient for extended data collection and offers the possibility of
      describing an individual's activity profile in a variety of circumstances.

PMID- 8761935
TI  - The effect on body temperature and melatonin of a 39-h constant routine with two
      different light levels at nighttime.
AB  - Eight healthy subjects were studied during 39-h spans (from 07:00 on one day
      until 22:00 the second) in which they remained awake. During one experiment,
      subjects were exposed to 100 lux of light between 18:00 and 8:00, and during a
      second experiment, they were exposed to 1000 lux during the same time span.
      Throughout the daytime period, they were exposed to normal daylight (1500 lux or
      more). The nighttime 1000-lux light treatment suppressed the melatonin metabolite
      aMT6s, while the 100 lux treatment did not. On the treatment day, the 1000 lux,
      in comparison to the 100 lux, light treatment resulted in both an elevated
      temperature minimum and a delay in its clock-time occurrence overnight. No real
      circadian phase shift in the temperature, urinary melatonin, or cortisol rhythms
      was detected after light treatment. This study confirmed that nocturnal exposure
      to lower light intensities is capable of modifying circadian variables more than
      previously estimated. The immediate effects of all-night light treatment are
      essentially not different from those of evening light. This may be important if
      bright light is used to improve alertness of night workers. Whether subsequent
      daytime alertness and sleep recovery are affected by the protocol used in our
      study remains to be determined.

PMID- 8761936
TI  - Temperature rhythm of patients with major affective disorders: reduced circadian
      period length.
AB  - The aim of the study was to explore circadian alterations of the temperature
      rhythm in adults with Major Affective Disorders (DSM III-R:296.xx). The axillary
      temperature of 56 inpatients was recorded (6-min intervals for at least a 48-h
      span) when major clinical symptoms occurred and thereafter during the remission.
      Periods (tau s) of the temperature rhythm were accurately quantified from
      individual time series by power spectra analyses. Twenty-seven subjects with no
      affective disorders served as controls. Histograms of the frequency distribution
      of tau s, chi square, and so forth were used as statistical methods. In both
      patients and controls a multimodal distribution of prominent tau s was observed.
      However, in controls this distribution showed the highest frequency (88.9%) with
      tau s = 24h, and seldom tau s < 24h or tau s > 24h, while in patients with major
      affective disorders, tau s exhibited a statistically significant (x2 = 10.84; p <
      0.004) different distribution with the highest frequency for tau s < 24h in 50%
      of the patients. Subjects diagnosed as suffering from Major Affective Disorders
      commonly exhibit a period shorter than 24h in the axillary temperature circadian
      rhythm suggestive of a desynchronized time structure.

PMID- 8761937
TI  - Effects of nocturnal shiftwork on mood states of student nurses.
AB  - Daily mood changes were monitored over successive 24-h periods using the Profile
      of Mood States (POMS) (3) to assess the effect of nocturnal shiftwork on mood.
      Twenty-three student nurses, age range 19-24 years, were studied throughout their
      first experience of nocturnal shiftwork. The POMS was administered over four
      complete solar days during a 12-week period that included an 8-week block of
      night work. Five POMS dimensions displayed circadian rhythmicity: vigor-activity;
      fatigue-inertia; confusion-bewilderment; friendliness; and total-mood
      disturbance. These five dimensions were sensitive to changes in living patterns,
      showing phase shifts in their circadian rhythms when subjects alternated between
      diurnal and nocturnal living patterns. The dimensions were also observed to be
      sensitive to adjustment to two different nocturnal shiftwork schedules. The
      subjects who worked "four on, three off" showed similar phase shifts to the
      subjects who worked "eight on, seven off," suggesting that mood adjustment takes
      place by the fourth night of a rotation of nights. The "commitment" of the
      students to the nocturnal living pattern was thought to have a bearing on the
      adaptation of the students to the nocturnal shifts, as regards mood.

PMID- 8761938
TI  - High activity, soluble, bacterially expressed human vitamin D receptor and its
      ligand binding domain.
AB  - The effects of 1 alpha, 25(OH)2 vitamin D3 on cell growth and differentiation are
      primarily mediated by the nuclear vitamin D receptor (VDR). In order to study
      aspects of receptor function and ultimately the structural basis of the VDR
      ligand interaction, it is necessary to produce large quantities of purified VDR.
      To achieve this, we have expressed the human VDR and its ligand binding domain in
      E. coli as fusion proteins with the maltose binding protein using the expression
      vector pMal-c2. In this system high level expression of both fusion proteins in a
      soluble form was achieved, whereas previous attempts to express the VDR in E.
      coli have resulted in an insoluble product. After affinity purification on
      amylose resin, the fusion proteins were isolated with yields of 10-20 mg/l of
      culture. Both forms of the recombinant receptor bound 1 alpha, 25(OH)2 vitamin D3
      with high affinity; estimated Kd values from Scatchard analysis for the purified
      full-length receptor and the ligand binding domain were 0.16 +/- 0.07 nM and 0.04
      +/- 0.02 nM, respectively. The nonhypercalcemic analogs of vitamin D, MC903 and
      delta 22-1, 25S, 26 (OH)3 vitamin D3, bound the recombinant fusion proteins with
      a similar affinity to the native ligand, 1 alpha, 25(OH)2 vitamin D3. In
      addition, the full-length VDR fusion protein was shown by gel shift analysis to
      bind weakly to the human osteocalcin gene vitamin D response element, an
      interaction greatly facilitated by addition of RXR alpha. These results show that
      the bacterial expression system detailed here is readily able to produce soluble
      and functional VDR and its ligand binding domain in high yield. These proteins
      are easily purified and should be suitable for further structural and functional
      analysis.

PMID- 8761939
TI  - Modulation of alpha 5 beta 1 and alpha V beta 3 integrins on the cell surface
      during mitosis.
AB  - One of the hallmarks of cells undergoing mitotic division is their rounded
      morphology and reduced adhesion to the substratum. We have studied and compared
      the attachment of interphase and mitotic cells to substrata coated with
      fibronectin and vitronectin. We have found that adhesion of mitotic cells, as
      compared to interphase cells, is significantly reduced to fibronectin, but is
      higher to vitronectin. These results correlate well with the expression of alpha
      5 beta 1 and alpha V beta 3 integrins, the respective receptors for fibronectin
      and vitronectin, on the cell surface. Mitotic cells show higher levels of alpha V
      beta 3 and very low levels of alpha 5 beta 1 proteins on the cell surface as
      compared to interphase cells. This difference in the levels of these integrins
      also reflects in the total amounts of fibronectin and vitronectin present on the
      cell surface of these cells. We have further shown, by flow cytometry, that
      binding of vitronectin, or the synthetic peptide -GRGDSP-, causes an increase in
      the intracellular levels of Ca2+ in mitotic cells, but no change is seen in the
      interphase cells. Binding of fibronectin to either of these cells fails to elicit
      any response. One interesting feature of our results is that the levels of total,
      i.e., cytoplasmic plus membrane bound, alpha 5 beta 1 and alpha V beta 3
      integrins of mitotic and interphase cells remain the same, thus implying an
      alteration in the distribution of integrin chains between the plasma membrane and
      the cytoplasm during the conversion of interphase cells into the mitotic phase.

PMID- 8761940
TI  - Transcriptional regulation of the lysozyme gene in airway gland serous cells.
AB  - Lysozyme is expressed in serous, but not mucous, cells of the tracheobronchial
      glands and thereby constitutes a marker of the serous cell lineage in these
      glands. To identify DNA regulatory elements and transcription factors mediating
      the commitment of progenitor cells to the serous cell lineage, we have
      characterized the regulatory activity and DNA-protein interactions of the 5'
      flanking region of the bovine lysozyme gene lys 5a. Results obtained from these
      studies indicate that although approximately 94 bp of 5'flanking DNA are
      necessary for high level expression in transient transfection assays, an
      evolutionarily conserved promoter within 66 bp of the transcription start site is
      sufficient to confer serous cell-specific expression. Farther upstream, within
      6.1 kb of the 5' flanking region, are 4 silencers. Analysis of the serous cell
      specific lysozyme promoter by electrophoretic mobility shift assay (EMSA)
      revealed the presence of binding sites for 3 serous cell nuclear proteins,
      designated LSF1, LSF2 and LSF3. Binding of LSF2 and LSF3 was localized to a 20
      mer subdomain (-50/-30) of the cell-specific promoter using binding competition
      assays. More accurate identification of the protein binding site(s) was achieved
      through the use of mutagenesis, which implicated the motif 5' AAGGAAT 3' (-46/
      40) in both protein binding and serous cell-specific transcriptional activity.
      This motif has previously been identified as a binding site for ets protein
      transcription factors, suggesting that serous cell-specific regulation of lys 5a
      transcription is partly controlled by the binding of ets-like protein(s) to the
      motif 5'AGGAAGT3'.

PMID- 8761941
TI  - Conversion of dermal fibroblasts to a myogenic lineage is induced by a soluble
      factor derived from myoblasts.
AB  - The limb and axial skeletal muscles of mammals originate from somitic
      dermomyotome, which during early development separates to form two discrete
      structures, the dermatome and the myotome. The latter cell mass gives rise to the
      muscle-forming lineage while cells of the dermatome will form the skin dermal
      fibroblast population of the dorsal regions of the body. It has been generally
      accepted for some time that myotome-derived myoblasts were the sole source of
      muscle fibre nuclei, but evidence has recently been presented from several
      laboratories that fibroblasts can fuse with myoblasts to contribute active nuclei
      to the resulting myotubes. We report here an investigation into the myogenic
      capacity of fibroblasts. Confluent monocultures of mouse dermal fibroblasts,
      muscle fibroblasts, and C2C12 myoblasts each retain their individual phenotype
      when maintained for periods up to 7 days in culture. We also grew isolated
      colonies of fibroblasts and myoblasts in an arrangement which allowed free
      exchange of tissue culture medium between the 2 cell types. We found evidence of
      the conversion of dermal fibroblasts to a myogenic lineage as measured by the
      appearance of MyoD-positive cells expressing the muscle-specific intermediate
      filament desmin. In addition, dermal fibroblast cultures contained multinucleate
      syncytia positive for MyoD and containing sarcomeric myosin heavy chain. In
      contrast, muscle-derived fibroblasts showed no evidence of myogenic conversion
      when maintained in identical culture conditions. We prepared conditioned medium
      from confluent cultures of C2C12 myoblasts and added this material to confluent
      monocultures of either dermal or muscle fibroblasts. While muscle fibroblasts
      showed no phenotypic alterations, cultures of dermal fibroblasts responded to
      myoblast conditioned medium by converting to a myogenic lineage as judged by
      expression of MyoD and desmin. We conclude that a proportion of dermal
      fibroblasts retain a myogenic capacity into stages well beyond their early
      association with myoblasts in the dermomyotome.

PMID- 8761942
TI  - Chondrocyte cultures express matrix metalloproteinase mRNA and immunoreactive
      protein; stromelysin-1 and 72 kDa gelatinase are localized in extracellular
      matrix vesicles.
AB  - Previous studies have shown that costochondral cartilage cell cultures produce
      extracellular matrix vesicles which contain metalloproteinase activity. In the
      present study, we examined whether two matrix metalloproteinases (MMPs) known to
      be present in cartilage, stromelysin-1 and 72 kDa gelatinase, are expressed by
      fourth passage resting zone and growth zone costochondral chondrocytes and
      whether they are specifically incorporated into matrix vesicles produced by the
      cells. We also examined whether the cells synthesize tissue inhibitor of
      metalloproteinase-1 and -2 (TIMP-1 and TIMP-2). Oligonucleotide primers for
      stromelysin-1, 72 kDa gelatinase, tissue inhibitor of metalloproteinases-1 and -2
      (TIMP-1 and TIMP-2), and GAPDH were synthesized and optimized for use in the
      reverse transcription-polymerase chain reaction (RT-PCR). It was found that both
      resting zone and growth zone chondrocytes produced mRNA for both MMPs and the two
      TIMPs. Further, immunostaining of cell layers with antibodies to 72 kDa
      gelatinase and stromelysin-1 showed that both cell types produced these MMPs in
      culture. Substrate gel electrophoresis and Western analysis were used to
      characterize MMP activity in matrix vesicles, media vesicles, or plasma membranes
      as well as in conditioned media produced by the chondrocyte cultures. It was
      found that matrix vesicles but not plasma membranes or media vesicles were
      selectively enriched in stromelysin-1. Also, 72 kDa gelatinase was found in
      matrix vesicles, but to a lesser extent than seen in media vesicles. The relative
      activity of each enzyme detected was cell maturation-dependent. No MMP activity
      was detected in conditioned media produced by either cell type. The results of
      this study show that MMPs are expressed by resting zone and growth zone
      chondrocytes in culture and differentially distributed among three different
      membrane compartments. This suggests that, in addition to the well-known
      activators and inhibitors of MMP activity in the matrix, differential membrane
      distribution may enable more precise control over the site, rate, and extent of
      matrix degradation by the cell.

PMID- 8761943
TI  - Effect of transient overexpression of Gq alpha on soluble and polymerized tubulin
      pools in GH3 and AtT-20 cells.
AB  - In order to study Gq-tubulin interaction in the cytosol, GH3 and AtT-20 cells
      (stably expressing TRH receptor) were transiently transfected with Gq alpha cDNA.
      Forty-eight hours after transfection, thyrotropin-releasing hormone (TRH)
      stimulated prolactin (PRL) secretion by Gq alpha-transfected GH3 cells increased
      by 90% compared to mock-transfected cells. In addition, using immunocytochemistry
      it was observed that Gq alpha-specific staining was much more prominent in Gq
      alpha-transfected GH3 and AtT-20 cells (also transfected with Gq alpha) compared
      to mock-transfected cells. Thus, transfection resulted in successful
      overexpression of functional Gq alpha. Forty-eight hours after transfection,
      cells were processed to obtain soluble and polymerized tubulin fractions. Tubulin
      levels were determined in these fractions by immunoblotting using polyclonal anti
      tubulin antibodies. Compared to mock-transfected cells soluble tubulin levels
      decreased in Gq alpha-transfected GH3 and AtT-20 cells, by 33 and 52%,
      respectively. Moreover, compared to mock-transfected cells a 50% reduction in the
      ratio (an index of the flux between tubulin pools) of soluble and polymerized
      tubulin levels was observed in Gq alpha-transfected GH3 and AtT-20 cells. To
      determine whether these effects on tubulin were mediated by Gq directly, we
      examined the influence of purified Gq on tubulin polymerization. Gq (0.5 microM)
      inhibited polymerization of crude tubulin (present in GH3 cell cytosol) by 53%.
      In contrast to its effects on GH3 cell cytosol tubulin, Gq stimulated purified
      tubulin polymerization by 160%. These results suggest that Gq modulates the
      polymerization and depolymerization cycles of tubulin and that this modulation is
      in turn influenced by other unknown cellular components.

PMID- 8761944
TI  - Low-molecular-weight variants of osteopontin generated by serine proteinases in
      urine of patients with kidney stones.
AB  - Osteopontin (OPN) is a multifunctional glycosylated phosphoprotein found in body
      fluids, including urine, and has been implicated in urinary stone formation. We
      tested the hypothesis that OPN levels in urine of patients with kidney stones
      differed from normal individuals. To quantify OPN levels in the urine, we
      developed an ELISA using a combination of a mouse monoclonal and rabbit
      polyclonal antibodies raised against a recombinant glutathione-S-transferase
      human OPN fusion protein. In a group of 34 patients diagnosed with kidney stones
      compared with a control group of 23 normal individuals, we found that OPN levels
      in urine of the patient and control groups ranged from 0.01 to 2.7 micrograms/ml,
      with no significant difference in their medians (P > 0.8, Mann-Whitney test). OPN
      in urine was qualitatively assessed by Western blotting using a biotinylated
      monoclonal antibody to detect various molecular forms. The urine of most
      individuals contained OPN species within in the 55- to 66-kDa electrophoretic
      mobility range. However, a significantly higher proportion of individuals in the
      patient group (13 of 34) was found to have aberrant urine OPN species (< or = 40
      kDa) compared to 2 of 23 for the control group (P < 0.03, chi 2 test). Mixing
      experiments indicated that urine samples with aberrant OPN contain proteases
      inhibitable with phenylmethylsulfonyl fluoride. Such proteases could break down
      normal urine OPN in vitro. Therefore, urine from a high frequency of kidney stone
      patients contains serine proteases that contribute to proteolytic cleavage of
      OPN.

PMID- 8761945
TI  - Selenium-regulated translation control of heterologous gene expression: normal
      function of selenocysteine-substituted gene products.
AB  - In eukaryotes, the synthesis of selenoproteins depends on an exogenous supply of
      selenium, required for synthesis of the novel amino acid, selenocysteine, and on
      the presence of a "selenium translation element" in the 3' untranslated region of
      mRNA. The selenium translation element is required to re-interpret the stop
      codon, UGA, as coding for selenocysteine incorporation and chain elongation.
      Messenger RNA lacking the selenium translation element and/or an inadequate
      selenium supply lead to chain termination at the UGA codon. We exploited these
      properties to provide direct translational control of protein(s) encoded by
      transfected cDNAs. Selenium-dependent translation of mRNA transcribed from target
      cDNA was conferred by mutation of an in-frame UGU, coding for cysteine, to UGA,
      coding for either selenocysteine or termination, then fusing the mutated coding
      region to a 3' untranslated region containing the selenium translation element of
      the human cellular glutathione peroxidase gene. In this study, the biological
      consequences of placing this novel amino acid in the polypeptide chain was
      examined with two proteins of known function: the rat growth hormone receptor and
      human thyroid hormone receptor beta 1. UGA (opal) mutant-STE fusion constructs of
      the cDNAs encoding these two polypeptides showed selenium-dependent expression
      and their selenoprotein products maintained normal ligand binding and signal
      transduction. Thus, integration of selenocysteine had little or no consequence on
      the functional activity of the opal mutants; however, opal mutants were expressed
      at lower levels than their wild-type counterparts in transient expression assays.
      The ability to integrate this novel amino acid at predetermined positions in a
      polypeptide chain provides selenium-dependent translational control to the
      expression of a wide variety of target genes, allows facile 75Se radioisotopic
      labeling of the heterologous proteins, and permits site-specific heavy atom
      substitution.

PMID- 8761946
TI  - Phorbol myristate acetate transactivates the avian beta 3 integrin gene and
      induces alpha v beta 3 integrin expression.
AB  - 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3)transactivates the avian beta 3 integrin
      gene whose promoter contains at least two vitamin D response elements, one of
      which is in close proximity to a candidate AP1 site (TGACTCA). Since fos/jun and
      steroid hormones interact to regulate gene expression, we asked whether phorbol
      12-myristate-13-acetate (PMA), which stimulates binding of fos/jun to AP1 sites,
      transactivates the avian beta 3 integrin gene and, if so, does the phorbol ester
      modulate 1,25(OH)2D3 induction of the gene. We find the candidate AP1 sequence
      comigrates with the consensus AP1 sequence on electromobility shift assay when
      incubated with recombinant c-jun protein. Furthermore, PMA prompts expression of
      beta 3 integrin mRNA in the avian monocytic line, HD11. The increase in message
      reflects transactivation of the beta 3 gene and is mirrored by plasma membrane
      appearance of the integrin heterodimer alpha v beta 3. Moreover, attesting to the
      functional significance of PMA-enhanced alpha v beta 3 expression, cells treated
      with concentrations of the phorbol ester that induce the beta 3 gene, spread
      extensively on plastic, an event blocked by an anti-alpha v antibody and a
      peptide mimetic known to inhibit alpha v beta 3-mediated cell attachment.
      Interestingly, co-addition of 1,25(OH)2D3 and PMA prompts greater expression of
      alpha v beta 3 than when the cells are exposed to either agent alone and PMA
      enhances 1,25(OH)2D3-induced beta 3 integrin mRNA expression. Thus, PMA and
      1,25(OH)2D3 impact on the avian beta 3 integrin gene independently and in
      combination.

PMID- 8761947
TI  - Regulation of urokinase-type plasminogen activator expression by an ERK1
      dependent signaling pathway in a squamous cell carcinoma cell line.
AB  - The urokinase-type plasminogen activator contributes to tissue remodeling by
      controlling the synthesis of the extracellular matrix-degrading plasmin. We
      undertook a study to determine the role of the extracellular signal-regulated
      kinases (ERKs) in the regulation of urokinase-type plasminogen activator
      expression in a squamous cell carcinoma cell line (UM-SCC-1) that contains a
      transcriptionally activated urokinase-type plasminogen activator gene. Transient
      transfection studies using a CAT reporter driven by the urokinase-type
      plasminogen activator promoter, which had progressive 5' deletions or which had
      been point-mutated, indicated the requirement of binding sites for AP-1 (-1967)
      and PEA3 (-1973) for its maximal activation. Expression of a mutant jun protein,
      which lacks the transactivation domain, caused a dose-dependent repression of a
      CAT reporter driven by either the urokinase-type plasminogen activator promoter
      or three tandem AP-1 repeats upstream of a thymidine kinase minimal promoter
      indicating the importance of AP-1-binding transcription factor(s) in the
      regulation of urokinase-type plasminogen activator synthesis. Mobility shift
      assays with UM-SCC-1 nuclear extract revealed binding of fos and junD proteins to
      an oligonucleotide spanning the AP-1 site at -1967. In-gel kinase assays
      indicated the constitutive activation of ERK1, which regulates fos synthesis via
      phosphorylation of p62TCF, but not ERK2, in UM-SCC-1 cells. Moreover, the
      expression of a dominant-negative ERK1, but not ERK2, repressed urokinase-type
      plasminogen activator promoter activity. Similarly, interfering with the function
      of the c-raf serine-threonine kinase, which lies upstream of ERK1, by the
      expression of a kinase-inactive c-raf repressed the activity of a CAT reporter
      driven by either the urokinase-type plasminogen activator promotor or tandem AP-1
      repeats. These data suggest that urokinase-type plasminogen activator expression
      in UM-SCC-1 cells is regulated partly by an ERK1, but not ERK2, -dependent
      signaling pathway.

PMID- 8761948
TI  - Application of an in vitro system in the study of chemotherapeutic drug effects
      on DNA replication.
AB  - DNA replication machinery is an important target for chemotherapeutic drugs. We
      have used an in vitro system to study the effect of drugs on mammalian DNA
      replication, either by direct interaction with the DNA structure or with
      replication proteins and machinery. The anthracycline doxorubicin (Dox) showed a
      dose-dependent inhibitory effect on DNA replication, whether incubated with HeLa
      cell extracts or with DNA and nucleotides. Earliest-labeled fragment analysis
      revealed that inhibition of replication began within the origin-containing
      fragment in both control and Dox-containing reactions in vitro. AraC, a
      nucleoside analog, had no significant effect on DNA synthesis. In contrast,
      araCTP was able to inhibit DNA replication in vitro. Since metabolism is
      diminished in this in vitro system, the degree of phosphorylation of araC was
      apparently low. Progesterone showed an increase in nucleotide incorporation
      (sensitive to BuPdGTP inhibition of replication-specific polymerases alpha and
      delta) after preincubation with HeLa cell extracts, although progesterone
      receptors were not detectable in the HeLa cell extracts. In addition, we observed
      an inhibition in DNA replication when progesterone was preincubated with DNA and
      nucleotides. These results suggest that progesterone may have a mechanism of
      action that is different from any known to be mediated through progesterone
      receptors. In conclusion, these results indicate that this mammalian in vitro
      replication system will be useful for the study of mechanisms and design of
      therapeutic drugs that inhibit mammalian DNA replication.

PMID- 8761949
TI  - Integrin-dependent role of human T cell matrix metalloproteinase activity in
      chemotaxis through a model basement membrane.
AB  - Human T lymphoblastoma cells of the CD4+ 8+ Tsup-1 line, that express alpha 4 and
      alpha 5 but not alpha 6 integrins of the beta 1 family, and CD4+ human blood T
      cells bind vasoactive intestinal peptide (VIP) with high affinity, leading to
      increased adherence, secretion of matrix metalloproteinases (MMPs), and
      chemotaxis. VIP-enhanced adherence of T cells to fibronectin was inhibited
      significantly by neutralizing monoclonal antibodies to beta 1 > alpha 4 > > alpha
      5, but not to alpha 6. Antibodies to beta 1 and alpha 4 suppressed to a similarly
      significant extent VIP stimulation of both MMP-dependent T cell chemotaxis
      through fibronectin-enriched Matrigel and T cell degradation of 3H-type IV
      collagen in the Matrigel, without affecting VIP-evoked secretion of MMP by
      suspensions of T cells. The lesser inhibition of VIP-enhanced adherence of T
      cells to fibronectin by anti-alpha 5 antibody, than antibodies to beta 1 or alpha
      4 chains, was associated with lesser or no suppression of MMP-dependent T cell
      chemotaxis through Matrigel and T cell degradation of type IV collagen in the
      Matrigel in response to VIP. Specific beta 1 integrins thus mediate interactions
      of stimulated T cells with basement membranes, including adherence, localized
      digestion by MMPs, and chemotactic passage, that promote entry of T cells into
      extravascular tissues.

PMID- 8761950
TI  - Mammalian CAP interacts with CAP, CAP2, and actin.
AB  - We previously identified human CAP, a homolog of the yeast adenylyl cyclase
      associated protein. Previous studies suggest that the N-terminal and C-terminal
      domains of CAP have distinct functions. We have explored the interactions of
      human CAP with various proteins. First, by performing yeast two-hybrid screens,
      we have identified peptides from several proteins that interact with the C
      terminal and/or the N-terminal domains of human CAP. These peptides include
      regions derived from CAP and BAT3, a protein with unknown function. We have
      further shown that MBP fusions with these peptides can associate in vitro with
      the N-terminal or C-terminal domains of CAP fused to GST. Our observations
      indicate that CAP contains regions in both the N-terminal and C-terminal domains
      that are capable of interacting with each other or with themselves. Furthermore,
      we found that myc-epitope-tagged CAP coimmunoprecipitates with HA-epitope-tagged
      CAP from either yeast or mammalian cell extracts. Similar results demonstrate
      that human CAP can also interact with human CAP2. We also show that human CAP
      interacts with actin, both by the yeast two-hybrid test and by
      coimmunoprecipitation of epitope-tagged CAP from yeast or mammalian cell
      extracts. This interaction requires the C-terminal domain of CAP, but not the N
      terminal domain. Thus CAP appears to be capable of interacting in vivo with other
      CAP molecules, CAP2, and actin. We also show that actin co-immunoprecipitates
      with HA-CAP2 from mammalian cell extracts.

PMID- 8761951
TI  - Association of transcription factors with the nuclear matrix.
AB  - The nuclear matrix is the framework scaffolding of the nucleus and has been
      demonstrated to be an important component in a number of nuclear processes
      including transcription, replication, and RNA splicing and transport. In the
      interphase nucleus, DNA is specifically organized in a three-dimensional fashion.
      An example of this fact is that actively transcribed genes have been demonstrated
      to associate with the nuclear matrix. In this study, nuclear matrix proteins from
      various rat tissues, including two androgen-regulated tissues, the seminal
      vesicle and ventral prostate, were examined to determine if they contained
      proteins that associate with consensus binding sequences for several proteins
      involved in the regulation of transcription. Specific interactions were
      identified between proteins of the nuclear matrix and these transcriptional
      activator binding sequences. In addition, the sizes of the complexes binding to
      the DNA sequences appeared to vary in some of the tissues. These data support the
      concept that the nuclear matrix may serve as a support structure to bring
      together specific DNA sequences with factors involved in the regulation of gene
      expression.

PMID- 8761952
TI  - Expression of basic helix-loop-helix transcription factors in explant
      hematopoietic progenitors.
AB  - The basic helix-loop-helix (bHLH) transcription factors form heterodimers and
      control steps in cellular differentiation. We have studied four bHLH
      transcription factors, SCL, lyl-1, E12/E47, and ld-1, in individual lineage
      defined progenitors and hematopoietic growth factor-dependent cell lines,
      evaluating mRNA expression and the effects of growth factors and cell cycle phase
      on this expression. Single lineage-defined progenitors selected from early murine
      colony starts and grown under permissive conditions were analyzed by RT-PCR. SCL
      and E12/E47 were expressed in the vast majority of tri-, bi-, and unilineage
      progenitors of erythroid, macrophage, megakaryocyte, and neutrophil lineages.
      Expression for E12/E47 was not seen in unilineage megakaryocyte and erythroid or
      bilineage neutrophil/mast cell progenitors. Lyl-1 showed a more restricted
      pattern of expression, although expression was seen in some bi- and unilineage
      progenitors. No expression was detected in erythroid, erythroid-megakaryocyte
      macrophage, macrophage-neutrophil, macrophage, or megakaryocytic progenitors. Id
      1, an inhibitory bHLH transcription factor, was also widely expressed in all bi-
      and unilineage progenitors; only the trilineage erythroid-megakaryocyte
      macrophage progenitors failed to show expression. Expression of these factors
      within a progenitor class was generally heterogeneous, with some progenitors
      showing expression and some not. This was seen even when two sister cells from
      the same colony start were analyzed. Id-1, but not E12/E47, mRNA was increased in
      FDC-P1 and MO7E hematopoietic cell lines after exposure to IL-3 or GM-CSF. Id-1,
      E12, and lyl-1 showed marked variation at different points in cell cycle in
      isoleucine-synchronized FDC-P1 cells. These results suggest that SCL, lyl-1,
      E12/E47, and Id-1 are important in hematopoietic progenitor cell regulation, and
      that their expression in hematopoietic cells varies in response to cytokines
      and/or during transit through cell cycle.

PMID- 8761953
TI  - The advantage of using positron emission tomography in drug research.
AB  - A large problem in drug discovery is to find relevant in vitro or in vivo animal
      models and to be able to extrapolate the results obtained to humans. Drug
      research now benefits from the fast development of imaging technologies that
      trace radiolabelled molecules directly in the human brain. Positron emission
      tomography (PET) and allied techniques use molecules that are labelled with short
      lived radioisotopes and injected intravenously. The most straightforward approach
      is to radiolabel a new potential drug and then to trace its anatomical
      distribution and binding in the brain. An indirect approach is to study how the
      unlabelled drug inhibits specific radioligand binding. The demonstration of
      quantitative relationships between drug binding in vivo and drug effects in
      patients is used to validate targets for drug action and to optimize clinical
      treatment.

PMID- 8761954
TI  - Mechanisms for the generation of synapse specificity in long-term memory: the
      implications of a requirement for transcription.
AB  - Since long-term memory (LTM) depends on transcription, signals required for LTM
      must emanate from the cell body. In some cases, signals from the cell body are
      not only required, but are also sufficient for LTM. However, It is difficult to
      reconcile this finding with the need to modify synapses independently. To retain
      synapse specificity during LTM, a form of memory is required that is independent
      of transcription, and that produces a synaptic 'mark' which interacts with
      molecules synthesized in the cell body. To reconcile the sufficiency of
      transcriptional signals for LTM with the need for synapse specificity, I propose
      that not all LTM is synapse-specific; activation of transcription presynaptically
      results in cell-wide LTM, whereas postsynaptic transcriptional activation leads
      to synapse-specific LTM.

PMID- 8761955
TI  - Function of metabotropic glutamate receptors in learning and memory.
AB  - Learning is the modification of behaviour by experience, and memory is the
      retention of such modifications. Since learning events might be of short
      duration, selective neuronal mechanisms must exist to translate transient
      activity into long-lasting memory. Because metabotropic glutamate (mGlu)
      receptors are coupled to various second messenger cascades they are ideal
      candidates for such translations. Their involvement in synaptic plasticity has
      been demonstrated recently, an important finding given that changes in synaptic
      efficacy are widely believed to be the physical substrate for information
      storage. Behavioural investigations using selective drugs have demonstrated that
      memory formation, especially of hippocampus-dependent tasks, is blocked by pre
      training treatment with both mGlu-receptor agonists and antagonists. In contrast,
      agonists administered post-training might amplify memory formation. The
      hypothesis put forward here suggests that the primary function of mGlu receptors
      is to set the signal-to-noise ratio and thereby filter out unimportant or amplify
      important information.

PMID- 8761956
TI  - Apolipoprotein E, memory and Alzheimer's disease.
AB  - Apolipoprotein E (ApoE) epsilon 4 is a well-documented risk factor for
      Alzheimer's disease (AD). Patients with AD show neuronal damage, particularly in
      the medial temporal lobe structures involved in memory processing. ApoE has been
      implicated in nerve regeneration following injury, and synaptogenesis in the
      hippocampus of experimental animals. Recent studies have shown an increased
      accumulation of beta A4 amyloid and an increased deficit in ACh-containing
      neurons in the brains of AD patients that are homozygous for ApoE epsilon 4
      compared with those lacking epsilon 4. Furthermore, AD patients with two ApoE
      epsilon 4 alleles have more-severe loss in hippocampal volume in magnetic
      resonance imaging (MRI) scans, and more impairment in tests assessing delayed
      memory, than AD patients without the epsilon 4 allele, in spite of similar global
      severity of dementia. Minor changes in hippocampal MRI volumetry can also be
      detected in nondemented elderly, particularly in those with an epsilon 4/4
      genotype. Data from a population-based study revealed that elderly subjects
      carrying the epsilon 4 allele had worse learning ability than those with the
      epsilon 2/2 or epsilon 2/3 phenotypes, whereas these groups did not differ in
      other cognitive domains. These data suggest that ApoE epsilon 4 might influence
      the magnitude of medial temporal lobe atrophy and memory impairment in AD and
      also in nondemented elderly.

PMID- 8761957
TI  - Immunostaining of neuropil for integrins.

PMID- 8761958
TI  - Regeneration of immature mammalian spinal cord after injury.
AB  - In this review we describe the growth of regenerating fibres through lesions in
      immature mammalian spinal cord. In newborn opossums and foetal rats, repair
      occurs rapidly and reliably without antibodies, implants or bridges of undamaged
      spinal cord. In the neonatal opossum one can compare recovery from lesions made
      to the CNS at various stages of development in the animal and in culture. As the
      CNS matures, the capacity for regeneration ceases abruptly. In particular, the
      extracellular matrix and molecules associated with glia have been shown to play a
      role in promoting and inhibiting regeneration. Major problems concern the
      precision with which regenerating axons become reconnected to their targets, and
      the specificity needed for recovery of function.

PMID- 8761959
TI  - Presynaptic receptors and the control of glutamate exocytosis.
AB  - When a typical glutamate-containing neurone fires, an action potential is
      propagated down the branching axon through more than a thousand varicosities. At
      each of these release sites the probability that a synaptic vesicle will be
      exocytosed into the synaptic cleft is individually controlled by means of
      presynaptic receptors: autoreceptors responding by positive or negative feedback
      to previously released transmitter, or heteroreceptors under the influence of
      other neurotransmitters or modulators. The simplest system in which to
      investigate presynaptic modulation is the isolated nerve terminal or synaptosome;
      studies with this preparation have revealed a complex interplay of signal
      transduction pathways.

PMID- 8761960
TI  - Molecular genetic approaches to nociceptor development and function.
AB  - The activation of peripheral nociceptors is the subject of intense scrutiny,
      because of its significance in pain regulation. Genetic approaches, including
      homology cloning, difference cloning and transgenic manipulation of mice are
      providing useful insights into nociceptor function. Recent work suggests that
      transcriptional regulators (for example, islet-I), which are expressed relatively
      selectively in sensory neurones, play a crucial role in defining cellular
      phenotype. Difference cloning has identified genes which encode both ligand-gated
      and voltage-gated ion channels expressed by small-diameter sensory neurones. The
      role of inflammatory mediators such as NGF in regulating nociceptor function has
      been clarified in mis-expression and deletion studies. An understanding of the
      mechanisms that regulate gene expression in nociceptors should provide new ways
      to manipulate nociceptor sensitivity, with potential significance for pain
      therapy.

PMID- 8761961
TI  - Brain chimeras in birds: application to the study of a genetic form of reflex
      epilepsy.
AB  - A strain of chicken, called here FEpi (for Fayoumi epileptic), bearing an
      autosomal recessive mutation, exhibits a form of reflex epilepsy with EEG
      interictal paroxysmal manifestations and generalized seizures in response to
      either light or sound stimulations. By using the brain chimera technology, we
      demonstrate here that the epileptic phenotype can be partially or totally
      transferred from an FEpi to a normal chick by grafting specific regions of the
      embryonic brain. The mesencephalon contains the generator of all epileptic
      manifestations whether they involve visual or auditory neuronal circuits, with
      the exception of the abnormal EEG which is transmitted exclusively by
      telencephalic grafts. This analysis supports the hypothesis that certain forms of
      human and mammalian epilepsies have a brainstem origin.

PMID- 8761962
TI  - Immunobiology of human uteroplacental macrophages--friend and foe?

PMID- 8761963
TI  - Functional expression of the plasma membrane serotonin transporter but not the
      vesicular monoamine transporter in human placental trophoblasts and
      choriocarcinoma cells.
AB  - We investigated the functional expression of the plasma membrane serotonin
      transporter and the vesicular monoamine transporter in choriocarcinoma cells and
      normal trophoblasts. The RBL 2H3 cells, a rat basophilic leukaemia cell line,
      which express both transporters were used for comparison. The choriocarcinoma
      cells JAr and BeWo were found to possess the plasma membrane serotonin
      transporter as assessed by the presence of serotonin transport activity in intact
      cells that was Na(+)-dependent and was sensitive to inhibition by tricyclic and
      non-tricyclic antidepressants. The activity of the vesicular monoamine
      transporter in these cells was determined by measuring serotonin transport in
      digitonin-permeabilized cells. The transport in permeabilized cells was very
      slow, was not stimulated by ATP and was insensitive to inhibition by reserpine.
      Under similar conditions, the vesicular monoamine transporter activity was
      demonstrable in RBL cells, which was stimulated by ATP and was inhibitable by
      reserpine, bafilomycin A1 (an inhibitor of the V-type H(+)-pump) and carbonyl
      cyanide p-trifluoromethoxy phenylhydrazone (a protonophore which dissipates
      transmembrane H+ gradients). In corroboration with these findings, mRNA
      transcripts hybridizable to the vesicular monoamine transporter cDNA probe were
      detectable in RBL cells but not in JAr choriocarcinoma cells. Similarly, there
      was no evidence for the expression of the vesicular monoamine transporter as
      assessed by Northern blot analysis in normal trophoblasts which were maintained
      in culture to differentiate to form multinucleated syncytial cells. It is
      concluded that the trophoblasts and choriocarcinoma cells express the plasma
      membrane serotonin transporter but not the vesicular monoamine transporter.

PMID- 8761964
TI  - Superfused microcarrier cultures of choriocarcinoma cells: a dynamic model for
      studying transport of glucose and amino acids.
AB  - We here describe a novel procedure for culturing BeWo and JAr choriocarcinoma
      cells on solid microcarrier beads. The regime developed to stir the beads
      resulted, after about 10 days, in small aggregates of two to six beads covered
      with a layer of differentiated cells. Bead aggregates were packed into small
      columns and superfused, providing a dynamic in vitro system for studying the
      uptake mechanisms for sugars and amino acids. The rapid, unidirectional uptake of
      tritiated L-phenylalanine, L-serine, L-arginine and D-glucose was determined,
      relative to an extracellular reference tracer, in cells superfused in 0.5 ml
      (range 0.3-0.8 ml) columns. Several sequential measurements could be made in the
      same column. Twenty-four hour pre-incubation with dexamethasone (0.25 microM) was
      found to increase the transport of D-glucose. Uptake of D-glucose was reduced by
      over 80 per cent following 20 min perfusion of the cells with 1 mM phloretin. Pre
      incubation with growth hormone (0.2 microgram/ml) decreased the transport of
      serine, whereas nicotine (0.5 microgram/ml) decreased both serine and
      phenylalanine uptake. Atropine (1 mM) or 5-oxoproline (0.5 mM) had no short-term
      effects on amino acid uptake. Insulin (12.5 mIU/ml) had no effect on the
      transport of the amino acids but caused a small but significant increase in
      glucose transport (P < 0.05). This model allows characterization of human
      trophoblast function without the complications resulting from the presence of
      other cell types in placental slices or fragments.

PMID- 8761965
TI  - The effect of hypoxia on term trophoblast: hormone synthesis and release.
AB  - Isolated trophoblast in culture remained viable when exposed to severe hypoxia
      (Po2 12-14 mmHg) for at least 72 h as indicated by trypan blue exclusion and the
      synthesis and secretion of metabolically labelled proteins. However, release of
      hCG, hPL, progesterone and estradiol was reduced to < 10 per cent when compared
      to trophoblast in normoxia (Po2 120-130 mmHg). hCG mRNA was also reduced
      demonstrating interruption of synthesis at transcription. Acute exposure to
      hypoxia (2 h) suppressed progesterone release but not hCG, whereas inhibitors of
      oxidative phosphorylation suppressed hCG release but not progesterone. hCG
      release increases progressively during culture in normoxia, peaking at 72 h.
      Exposure of trophoblast to hypoxia for 48 h after 24, 48 and 72 h in normoxia
      interrupted this progression but did not suppress hCG release. Progesterone
      release, in contrast, was reduced by hypoxia. Exogenous dibutyryl cAMP increased
      hCG and progesterone release by normoxic trophoblast but not by hypoxic cells.
      Trophoblast returned to normoxia after 24 h in hypoxia increased hCG and
      progesterone release, suggesting early recovery. Conservation of oxygen and ATP
      by reducing hormone synthesis may contribute to survival of trophoblast in
      hypoxia.

PMID- 8761966
TI  - High and low molecular weight kininogen and plasma prekallikrein/plasma
      kallikrein in villous capillaries of human term placenta.
AB  - This study examined the expression and presence of components of the kallikrein
      kinin system in human term placenta. Immunohistochemical studies localized H
      kininogen and plasma prekallikrein/plasma kallikrein to endothelial cells of
      placental villous capillaries. In larger placental blood vessels and umbilical
      cord, neither kininogens nor kallikreins were detected. High (H) and low (L)
      molecular weight kininogen, plasma prekallikrein and plasma kallikrein were
      detected by Western blot analysis in human term placenta and in maternal and
      fetal blood, whereas tissue kallikrein was not. Furthermore, mRNA of plasma
      prekallikrein was detected by reverse transcriptase-polymerase chain reaction (RT
      PCR) in placental homogenates, while mRNA of H-kininogen, L-kininogen and tissue
      kallikrein was not. Because H-kininogen and plasma prekallikrein circulate in a
      complexed form, we suggest that endothelial cells bind kininogen and plasma
      prekallikrein in which they are secreted by the fetal liver from fetal blood. The
      co-localization of kininogen and plasma prekallikrein/plasma kallikrein suggests
      that kinins could be generated locally in placental capillaries. When released,
      they may play a role in regulating placental blood flow and transplacental
      transport of substrates and metabolites.

PMID- 8761967
TI  - Arachidonate metabolism in human placenta, fetal membranes, decidua and
      myometrium: lipoxygenase and cytochrome P450 metabolites as main products in HPLC
      profiles.
AB  - Eicosanoids play a key role in pregnancy maintenance and parturition. We
      investigated the metabolism of arachidonic acid (AA) in short-term tissue
      cultures of placenta, fetal membranes, decidua and myometrium. Tissues were
      obtained from caesarean sections before the onset of labour after uncomplicated
      pregnancies. The released metabolites were analysed by high performance liquid
      chromatography (HPLC) and specific immunoassays. In radiotracer experiments
      tissues were labelled with [3H]-AA and metabolites released after incubation with
      calcium ionophore A23187 were profiled by HPLC. Decidua was more active in
      metabolizing AA (turnover 34 per cent) than myometrium (28 per cent), placenta
      (21 per cent) and fetal membranes (17 per cent). Main product in placenta,
      decidua and myometrium was 12-hydroxyeicosatetraeinoic (12-HETE) (decidua: 19 per
      cent of released radioactivity, myometrium 14 per cent, placenta 7 per cent).
      Fetal membranes formed 5-HETE as main product. Another major metabolite in
      placenta, fetal membranes and decidua was characterized by HPLC as 5(6)
      epoxyeicosatrienoic acid. Only myometrium released appreciable amounts of
      prostaglandins in form of 6-keto-prostaglandin F1 alpha. In non-radioactive
      experiments formation of eicosanoids from endogenous AA was investigated by HPLC
      (fluorescence- and UV-detection) and immunoassays. These experiments confirmed
      the high production of 12-HETE and the low formation of prostaglandins. Our
      results suggest that the biological role of AA-metabolites, other than
      prostaglandins, have as yet been underestimated.

PMID- 8761968
TI  - Prostaglandin H synthase-2 in human gestational tissues: regulation in amnion.
AB  - Using reverse transcriptase-polymerase chain reaction we have established that
      mRNAs for prostaglandin H synthases 1 and 2 (PGHS-1 and PGHS-2) are present in
      amnion, chorion and decidua from women both at term before and after the onset of
      labour and from women at 28-35 weeks of gestation before the onset of labour. By
      Western blot analyses we have demonstrated that epidermal growth factor,
      interleukin 1 beta and phorbol 12-myristate 13-acetate all increase PGHS-2
      amounts in amnion cells. The degree of stimulation caused by these substances
      (218-311 per cent) is less than the increase in prostaglandin production usually
      generated (five- to 10-fold). Hence we believe that these substances may have
      multiple sites of action in the pathways of arachidonic acid metabolism.

PMID- 8761969
TI  - Placental isoferritin as a marker of early abortion in pregnancies induced by in
      vitro fertilization.
AB  - The relatively high rate of early pregnancy loss in artificial reproductive
      technology-induced conceptions has driven researchers to seek for an efficient
      diagnostic tool for estimating the gestational risk in these cases. Monitoring
      early gestation normalcy using serial beta-human chorionic gonadotrophin (beta
      hCG) measurements requires several days before diagnosis can be established. The
      objective of this study was to determine whether placental isoferritin (PLF) can
      be used as a predictive marker of normal pregnancy development during early
      stages of in vitro fertilization (IVF)-induced pregnancy. Ninety-three
      consecutive IVF cycles were investigated. Blood samples for PLF (enzyme linked
      immunosorbent assay; ELISA) and beta hCG (radio-immunoassay; RIA) determination
      were obtained from all women on days 11, 13 and 15 following embryo transfer.
      Placental isoferritin was detectable in the serum 11 days after embryo transfer
      in IVF conception cycles. These levels were significantly higher in normally
      developing pregnancies (n = 18) than in cases which eventually aborted
      spontaneously (n = 9) during the first trimester (mean +/- s.d.; 33 +/- 28 U/mL
      as compared with 1 +/- 2 U/mL; P = 0.0004; Wilcoxon test; sensitivity 94.5 per
      cent, specificity 88.9 per cent, positive predictive value 89.9 per cent,
      negative predictive value 94.5 per cent). Moreover, in those patients who later
      aborted, lower than normal PLF levels were detected long before the decline in
      beta hCG titres was evident. Considering its suppressor activity, it is expected
      that PLF levels would be high at the initiation of normal pregnancy. This may
      explain the present finding of low PLF levels in abnormally developing IVF
      induced pregnancies. These preliminary data suggest that PLF can be used as a
      sensitive marker for detecting those cases destined to abort at a very early
      stage. However, further studies are still required on spontaneous conceptions,
      before this test can be recommended for routine clinical application.

PMID- 8761970
TI  - Implantation and early placentation in the one-humped camel (Camelus
      dromedarius).
AB  - The ovaries and uteri were removed from four pregnant camels on days 14, 25, 35
      and 56 after ovulation. The day 14 and 25 uteri were perfuse-fixed with 3 per
      cent glutaraldehyde: 3 per cent paraformaldehyde whereas the day 35 and 56
      specimens were opened dorsally for photography before biopsies of allantochorion
      attached to endometrium were taken and fixed in either 3 per cent glutaraldehyde:
      3 per cent paraformaldehyde or Bouin's fluid. Samples of each uterus were then
      processed and sectioned for light and transmission electron microscopy. By day 14
      the majority of the trophoblast had become closely apposed to the luminal
      epithelium of the endometrium to form the start of an epitheliochorial placenta
      with microvillar interdigitation initiated in some places. By day 25 a well
      developed microvillar junction had formed between the fetal and maternal tissues.
      The fetus was situated in the middle of the left uterine horn in the day 35 and
      56 specimens and, histologically, large multinucleate giant trophoblast cells had
      developed at frequent but irregular intervals along the, otherwise single-cell,
      trophoblast. These giant cells were often situated over the mouth of an
      endometrial gland but their actual function in pregnancy is not yet known.

PMID- 8761971
TI  - The distribution of tissue inhibitor of metalloproteinases-2 (TIMP-2) in the
      human placenta.
AB  - Matrix metalloproteinases (MMPs) secreted by human cytotrophoblasts are crucial
      for the invasion of the placental bed by these cells. The invasive growth of the
      trophoblast is similar to that of malignant tumours in many respects, but, unlike
      the latter, it is strictly controlled. Tissue inhibitors of metalloproteinases
      (TIMPs) have been postulated to play a role in the control of trophoblast
      invasion. In this immunohistochemical study, the distribution of TIMP-2 in the
      human placenta was investigated. In first trimester placenta, the
      cytotrophoblasts in columns exhibited strong cytoplasmic staining for TIMP-2.
      Villous cytotrophoblasts exhibited staining of moderate intensity with
      accentuation at the cell membrane, especially at the interfaces with the
      syncytiotrophoblast and the villous stroma. Staining of the cytoplasm and apical
      border of the syncytiotrophoblast was weak and focal. In term placenta, the few
      cytotrophoblasts present exhibited a staining pattern similar to that of the
      cytotrophoblasts in first trimester placenta, and there was marked linear
      staining of the syncytiotrophoblast at the interface with the stroma. Because it
      is the first trimester cytotrophoblast columns that invade the placental bed, the
      results demonstrate that the strongest immunoreactivity for TIMP-2 in the
      trophoblast is found in cells that are known to produce MMPs and exhibit an
      invasive growth pattern. These findings indicate that TIMP-2 may be involved in
      autoregulation of the invasive growth of the trophoblast.

PMID- 8761972
TI  - International disease surveillance: summary for 1995.

PMID- 8761973
TI  - Incidence, location and interrelationships between the sites of abscesses
      recorded in pigs at a bacon factory in Northern Ireland.
AB  - The position and incidence of all the abscesses detected during post mortem
      inspection of 75,130 bacon weight pigs were recorded. Abscesses were detected at
      one site only in 2.87 per cent of the carcases examined, and at more than one
      site in 0.26 per cent of the carcases. Tail biting was the cause of the infection
      in 61.7 per cent of all the carcases with lesions at more than one site. In
      almost all cases there was a statistically significant interrelationship between
      the visible abscesses at different sites.

PMID- 8761974
TI  - Use of the respiratory stimulant doxapram in southern elephant seals (Mirounga
      leonina).
AB  - The use of doxapram to stimulate breathing was examined in southern elephant
      seals chemically restrained with ketamine and xylazine. Animals which were
      breathing spontaneously received doxapram (approximately 0.5, 1, 2, or 4 mg/kg)
      or saline into the extradural intravertebral vein. Doxapram caused a dose
      dependent increase in the depth and rate of respiration which began within one
      minute, peaked after two minutes and lasted for up to five minutes. A dose of 2
      mg/kg appeared to be safe and effective for the stimulation of respiration, while
      4 mg/kg caused arousal and shaking. Doxapram (2 mg/kg) was tested on 14 occasions
      in animals which had developed apnoea during chemical restraint. Doxapram had no
      effect when administered into the extradural intravertebral vein and appeared to
      be of more benefit when administered directly into the lungs via an endotracheal
      tube, but it was not effective in all cases. There was evidence to suggest that
      the endotracheal tube prevented some of the animals from breathing. The effect of
      intubation and endotracheal doxapram administration was therefore examined in 19
      apnoeic and 31 spontaneously breathing seals. Intubation induced apnoea in
      animals at low levels of chemical restraint and endotracheal doxapram was
      unreliable for the stimulation of breathing.

PMID- 8761975
TI  - Papillary ductal adenocarcinoma in the mammary glands of two horses.
AB  - Mammary gland neoplasms in horses are uncommon and may initially be confused with
      mastitis. Masses from the mammary glands of two horses with chronic discharges
      were examined by cytology and histopathology. Both masses were diagnosed as
      papillary ductal adenocarcinomas with extensive intraductal and intralobular
      involvement and only focal infiltration of the adjacent stroma. Complementary
      immunohistochemical studies were made of both fresh and formalin-fixed tumour
      tissue, and attempts were made to assess the steroid receptor status of fresh
      tissue biochemically to assess the possibility of hormonal treatment as an
      adjunct to surgery. The results of these tests for oestrogen and progesterone
      receptors were negative.

PMID- 8761976
TI  - Evaluation of a commercial gE blocking ELISA test for detection of antibodies to
      infectious bovine rhinotracheitis virus.

PMID- 8761977
TI  - Porcine reproductive and respiratory syndrome virus: seminal transmission.

PMID- 8761978
TI  - Fatal microfilarial infection in red billed blue magpies (Urocissa
      erythrorhynchus).

PMID- 8761979
TI  - Meningeal carcinomatosis in a dog.

PMID- 8761980
TI  - Quarantine regulations.

PMID- 8761981
TI  - Quarantine regulations.

PMID- 8761982
TI  - Parapox virus infection of the grey squirrel.

PMID- 8761983
TI  - Cyclospora in non-human primates in Gombe, Tanzania.

PMID- 8761984
TI  - Ultraviolet lights for reptiles.

PMID- 8761985
TI  - Differential acute tolerance development to effects of nitrous oxide in humans.
AB  - The analgesic, subjective, and psychomotor effects of 0, 10, 20, 30, and 40%
      nitrous oxide in oxygen were studied in 10 volunteers to determine if acute
      tolerance developed differentially to these variables. In this prospective,
      randomized, crossover, double-blind study, volunteers inhaled either placebo
      (100% oxygen) or one of the aforementioned doses of nitrous oxide for 120 min.
      During this period, volunteers immersed their non-dominant forearm, for 3 min, in
      ice-cold water at 25, 70 and 115 min from the onset of the inhalation. At other
      prescribed time intervals throughout the session, mood and psychomotor
      performance were assessed. Subjects reported less pain intensity from the cold
      water stimulus and reported the pain bothered them less as a function of
      increasing nitrous oxide dose; in addition, this analgesia was significantly less
      as the inhalation period progressed (i.e., acute tolerance). Some subjective
      effects of nitrous oxide that could be considered hedonic in nature (elation,
      drug liking) also showed evidence of acute tolerance. In contrast, other
      subjective effects and the psychomotor-impairing effects of nitrous oxide did not
      change significantly during the inhalation period (i.c., no acute tolerance). The
      differential acute tolerance observed in this study suggests that different
      effects of nitrous oxide may be mediated by different neurochemical substrates.

PMID- 8761986
TI  - Do craniocervical and jaw motor nuclei receive input from the same population of
      reticular premotor neurons? A double labeling tracing study in the mallard (Anas
      platyrhynchos).
AB  - As part of a study concerning the organization of premotor areas in the medullary
      reticular formation in birds we used a fluorescent retrograde double labeling
      technique to localize the premotor neurons of the trigeminal (mV) and supraspinal
      motor nucleus (SSp). Diamidino Yellow injections in mV and Fast Blue injections
      in SSp demonstrated that mV and SSp do not share premotor neurons, but the
      premotor neurons form a mixed population in the ventromedial part of the
      parvocellular reticular formation.

PMID- 8761987
TI  - Direct isolation of ultra-late (C-fibre) evoked brain potentials by CO2 laser
      stimulation of tiny cutaneous surface areas in man.
AB  - In this study, it is reported that CO2 laser heat stimulation of tiny skin
      surface area (0.15 mm2) provides a unique method to directly and selectively
      activate C-fibre as assessed by the ultra-late brain potentials (peak latencies:
      N810, P996) evoked consistently across a set of stimulus energy levels. On a
      larger surface area (15.5 mm2), low energy stimulation also resulted in minute
      ultra-late potential, while higher intensities induced only late potentials
      related to A-delta fibre activity (peak latencies: N247, P394). The selective
      activation of C afferent sensory terminals in the skin by stimulation of tiny
      surface area is explained by their relative high density and lower activation
      threshold.

PMID- 8761988
TI  - PD-135158, a CCKB receptor antagonist, microinjected into the nucleus accumbens
      and the expression of conditioned rewarded behavior.
AB  - Cholecystokinin (CCK) has been localized in the nucleus accumbens (NAC) where it
      may interact with dopamine neurotransmission. NAC dopamine is involved in the
      control over behavior produced by conditioned rewards. The present experiment
      examines whether the blockade of CCKB receptors in the NAC with microinjection of
      PD-135158 (10 micrograms in 0.5 microliter) potentiates bar-pressing for stimuli
      previously associated with food reward. Intra-NAC microinjections of amphetamine
      (10 micrograms in 0.5 microliter) increased the number of bar presses for
      conditioned reward presentation. Furthermore, similar administration of PD-135158
      produced no significant effect on responding when administered alone but
      potentiated the level of amphetamine responding. These findings suggest that
      endogenous CCKB mechanisms in the NAC may normally inhibit dopamine function in
      reward-related behaviors.

PMID- 8761989
TI  - Antisense oligodeoxynucleotide attenuates in vivo expression of c-fos in the
      paraventricular hypothalamic nucleus of the rat brain.
AB  - The proto-oncogene, c-fos, is expressed in neurons in response to stimulation by
      growth factors, neurotransmitters, and immunocytokines. In order to determine
      whether interleukin-1 beta (IL-1 beta)-induced Fos protein expression in the
      paraventricular hypothalamic nucleus (PVN) can be reduced or eliminated by a c
      fos antisense oligodeoxynucleotide, rats were injected with c-fos antisense and
      Fos expression was examined immunocytochemically. Our results indicate that c-fos
      antisense oligodeoxynucleotide treatment decreases the density of Fos immuno
      labeled nuclei in the PVN following IL-1 beta administration. These data suggest
      that, with the use of antisense technology, it may be possible to determine the
      role of proto-oncogene proteins in specific brain areas.

PMID- 8761990
TI  - A novel gene selectively expressed in the cerebellum.
AB  - A cDNA clone encoding a novel protein (Cer-1) was isolated from a mouse
      cerebellar cDNA library. The deduced amino acid sequence of Cer-1 is not
      homologous to other sequences in the protein sequence data base. RNA blot
      analysis suggests that expression of Cer-1 RNA occurs selectively in the adult
      cerebellum and in purified cultures of cerebellar granule neurons. An increase in
      its expression correlates with the timing of granule neuron differentiation in
      the cerebellum. Thus, the expression of Cer-1 may provide a selective marker for
      terminal differentiation of cerebellar granule neurons.

PMID- 8761991
TI  - Single neurons in Barrington's nucleus projecting to both the paraventricular
      thalamic nucleus and the spinal cord by way of axon collaterals: a double
      labeling study in the rat.
AB  - Barrington's nucleus, a center for the micturition reflex in the pontine
      tegmentum, was recently reported to send projection fibers to the paraventricular
      thalamic nucleus (PVT). In the present study, we examined whether or not
      Barrington's nucleus neurons projecting to the PVT issue axon collaterals to the
      lowest lumbar cord segment (L6) containing the spinal micturition center. Our
      retrograde double-labeling study revealed that a subset of Barrington's nucleus
      neurons send projection fibers to both the L6 and the thalamic midline including
      the PVT via axon collaterals. Such neurons projecting directly to the thalamic
      midline and L6 by way of axon collaterals were additionally scattered in the
      locus coeruleus, subcoeruleus nucleus and sublaterodorsal nucleus.

PMID- 8761992
TI  - Cerebral cortical neurons with activity linked to central neurogenic spontaneous
      and evoked elevations in cerebral blood flow.
AB  - We recorded neurons in rat cerebral cortex with activity relating to the
      neurogenic elevations in regional cerebral blood flow (rCBF) coupled to
      stereotyped bursts of EEG activity, burst-cerebrovascular wave complexes,
      appearing spontaneously or evoked by electrical stimulation of rostral
      ventrolateral medulla (RVL) or fastigial nucleus (FN). Of 333 spontaneously
      active neurons only 15 (5%), in layers 5-6, consistently (P < 0.05, chi-square)
      increased their activity during the earliest potential of the complex,
      approximately 1.3 s before the rise of rCBF, and during the minutes-long
      elevation of rCBF elicited by 10 s of stimulation of RVL or FN. The results
      indicate the presence of a small population of neurons in deep cortical laminae
      whose activity correlates with neurogenic elevations of rCBF. These neurons may
      function to transduce afferent neuronal signals into vasodilation.

PMID- 8761993
TI  - No association between very low density lipoprotein receptor (VLDL-R) and
      Alzheimer disease in American Caucasians.
AB  - The very low density lipoprotein receptor gene (VLDL-R) is a receptor for
      apolipoprotein-epsilon (APOE)-containing lipoproteins, and thus has been
      suggested as a possible risk factor for Alzheimer disease (AD). Recently,
      Okuizumi et al. [Nature Genet, II (1995) 207-209] reported an association between
      the 96 bp allele at the VLDL-R locus and AD in a Japanese population. The
      association resulted in a two-fold increase of risk that decreased with
      increasing age. We have examined this association in 316 Caucasian sporadic AD
      patients, comparing their findings to 160 Caucasian AD spouse controls. We also
      investigated 53 late-onset Caucasian AD families for association and linkage. Our
      data failed to confirm linkage and/or association to the VLDL-R locus.
      Stratification by age at onset or APOE genotype also failed to show significant
      results.

PMID- 8761994
TI  - Cortical ballooned neurons in progressive supranuclear palsy.
AB  - We report the presence of ballooned neurons (BNs) in the cerebral cortex of
      patients with progressive supranuclear palsy (PSP) using immunohistochemistry for
      phosphorylated neurofilament in addition to standard histologic staining methods.
      In six of the nine patients studied. BNs were seen in the cerebral cortex. In two
      of these six patients. BNs were abundant and cortical degeneration was present in
      the precentral cortex. On immunohistochemistry. BNs were positive for
      phosphorylated neurofilament and alpha B crystallin, and some BNs were positive
      for ubiquitin and tau protein. The immunohistochemical staining pattern was
      similar to that of the BNs seen in other diseases, such as corticobasal
      degeneration. The presence of cortical BNs does not differentiate PSP from
      corticobasal degeneration although BNs are fewer in the patients with PSP when
      cortical degeneration is not present.

PMID- 8761995
TI  - Effects of adrenodemedullation and adrenalectomy on the 5-HT2 receptor agonists
      DOI-and mCPP-induced hypophagia in rats.
AB  - Effects of adrenodemedullation and adrenalectomy on the serotonin2 (5-HT2)
      receptor agonists-induced hypophagia were investigated. Hypophagia induced by
      both the 5-HT2A/2C, receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane (DOI) and the 5-HT2C-receptor agonist 1-(3-chlorophenyl)piperazine
      (mCPP) were not affected by adrenodemedullation. In adrenalectomized rats. DOI
      did not induce hypophagia, while mCPP elicited apparent effects. These results
      suggest that neither DOI- nor mCPP-induced hypophagia was not associated with
      adrenaline release from the adrenal medulla. Moreover, our results suggest that
      DOI-induced hypophagia is involved in corticosterone-sensitive feeding, although
      other mechanisms which are not related to corticosterone are involved in mCPP
      induced anorexia.

PMID- 8761996
TI  - Choroid plexus: the major site of mRNA expression for the beta-trace protein
      (prostaglandin D synthase) in human brain.
AB  - Expression of beta-trace protein (beta-trace), recently identified as glutathion
      independent prostaglandin D synthase (prostaglandin-H2 D-isomerase; EC 5.3.99.2),
      was localized in paraffin sections of the human brain by in situ hybridization
      using digoxigenin-labeled antisense cRNA probes. The mRNA for beta-trace was
      predominantly found in the epithelial cells of the choroid plexus. Hybridization
      signals were also obtained in some oligodendrocytes, particularly in the white
      matter. In the leptomeninges, specific signals were found in meningeal
      macrophages and in single cells of the arachnoid barrier layer. The cells
      exhibiting hybridization signals with the antisense cRNA probes for beta-trace
      were identified by counterstaining with antibodies directed against specific cell
      markers. Additionally, beta-trace mRNA was localized in tubular epithelial and
      basal cells of the human epididymis and in different cell types within the
      seminiferous epithelium of the testis.

PMID- 8761997
TI  - Epileptiform activity and hippocampal damage produced by intrahippocampal
      injection of guanidinosuccinic acid in rat.
AB  - Guanidinosuccinic acid (GSA) is a guanidino compound found in mammalian central
      nervous system and physiological fluids. Its level has been found to be greatly
      increased in serum and cerebrospinal fluid of patients with renal failure, and
      the compound is suggested to play a role in uremic encephalopathy. In this report
      we examined the behavioral, electrographic and morphological effects of
      intrahippocampal GSA injection in unanesthetized rats. Intrahippocampal
      administration of 2 microliters GSA solution (3.5 nM) was followed by behavior
      observation, and electrohippocampographic and electrocorticographic recording.
      GSA-injected animals showed partial clonic seizures leading to generalized clonic
      seizures, and eventually status epilepticus. These were accompanied by
      epileptiform electrographic discharges. During generalized clonic seizures, the
      electrohippocampogram showed arythmic bursting spikes. Epileptiform electric
      activity persisted even after the generalized clonic convulsions had stopped, and
      lasted until the animals were killed, 5 days following injection. Microscopic
      examination of brain slices of these rats revealed severe neural damage in CA1
      area of hippocampus. Treatment of rats with the non-competitive NMDA receptor
      antagonist ketamine prevented both partial and generalized clonic seizures,
      epileptiform electrographic discharges, and GSA-induced hippocampal damage.

PMID- 8761998
TI  - Preprovasopressin mRNA is not present in dorsal root ganglia of the rat.
AB  - Immunohistochemical studies on colchicine-treated rats have suggested that more
      than half of the neurons in dorsal root ganglia (DRG) contain vasopressin. Thus,
      vasopressin would be the most commonly found peptide in DRG neurons. In the
      present study we have reexamined the presence of vasopressin in DRG neurons,
      using a sensitive in situ hybridization method employing long riboprobes that
      will detect very small amounts of mRNA. The C3, C6, T2, T12, L2 and L5 DRG were
      studied. None of these ganglia contained any preprovasopressin mRNA. Yet, dense
      labeling for preprovasopressin mRNA was seen on simultaneously processed
      hypothalamic sections and a heavy preprotachykinin mRNA expression was seen in
      adjacent DRG sections. These findings demonstrate that vasopressin is not
      produced in DRG in normal rats.

PMID- 8761999
TI  - Glutamine stimulates gamma-aminobutyric acid synthesis in synaptosomes but other
      putative astrocyte-to-neuron shuttle substrates do not.
AB  - GABAergic neurons require a supply of precursor glutamate for gamma-aminobutyric
      acid (GABA) synthesis to maintain their GABA levels. Because neurons lack the
      anaplerotic enzymes necessary for net synthesis of glutamate from glucose, they
      depend on astrocytes to supply compounds that can be metabolized to glutamate and
      ultimately used for GABA production. To test the effect of putative astrocytic
      shuttle metabolites on GABA synthesis, we used synaptosomes prepared from
      substantia nigra, an area rich in GABAergic terminals. The low number of
      glutamatergic endings in the nigral preparation allows a more accurate
      measurement of glutamate present in GABAergic endings. GABA synthesis by nigral
      synaptosomes was stimulated 3.1-fold when 500 microM glutamine was added to the
      incubation medium. Glutamate amounts also increased. In contrast, the possible
      precursor metabolites. 2-oxoglutarate (2-OG), malate and citrate, failed to
      stimulate GABA synthesis over the rate observed with control medium. Unlike
      malate and citrate. 2-OG reduced the decline in total glutamate observed when
      synaptosomes were incubated in control. In contrast to glutamine the production
      of synaptosomal glutamate from 2-OG, malate, and citrate is not great enough to
      stimulate GABA synthesis.

PMID- 8762000
TI  - Developmental age-dependent upregulation of choline acetyltransferase and
      vesicular acetylcholine transporter mRNA expression in neonatal rat septum by
      nerve growth factor.
AB  - We examined the effect of intraventricular injection of nerve growth factor (NGF)
      on the choline acetyltransferase (ChAT) and vesicular acetylcholine transporter
      (VAChT) mRNA expression in the septa of neonatal rats. Rat pups were injected
      with 2.5 S NGF or cytochrome-c (control) on postnatal days (PN) 4 and 18, and
      sacrificed 3 days after injections for analysis of ChAT and VAChT mRNA levels by
      dot-blot hybridization of total septal RNA. In the NGF-treated pups, the ChAT and
      VAChT mRNA levels were elevated 3- and 2-fold, respectively, at PN7, and 1.8- and
      1.3-fold at PN21. These results indicate that (1) NGF upregulates the expression
      of both ChAT and VAChT genes, (2) NGF has a greater effect on the expression of
      ChAT mRNA than VAChT mRNA, and (3) the effect of exogenous NGF on the expression
      of both genes diminishes with developmental age.

PMID- 8762001
TI  - Nitric oxide synthase levels in obese Zucker rats.
AB  - Nitric oxide has been demonstrated to play a role in the modulation of food
      intake. The Zucker fatty rat is an autosomal recessive genetic model of obesity.
      We measured nitric oxide synthase (NOS) in the hypothalamus and fundus of the
      stomach in Zucker (fa/fa) rats and their lean littermate controls (fa/?). NOS
      activity was decreased in both the hypothalamus and the fundus of the Zucker
      (fa/fa) rats compared to the littermate controls.

PMID- 8762002
TI  - Neuropathic pain in neonatal rats.
AB  - The aim of this study was to determine if peripheral nerve injury in neonatal
      rats triggers neuropathic pain behaviors as it does in adults. The injury was
      produced in three groups of neonatal rats (1, 2, and 3 weeks old) by tightly
      ligating the left L5 and L6 spinal nerves. Behavioral tests for mechanical
      allodynia were conducted from the 15th day after birth for the 1- and 2-week
      groups, and 1 day after surgery for the 3-week group. Rats in the 3-week group
      developed behaviors representing mechanical allodynia as is seen in adults. For
      the younger animals, however, the signs of mechanical allodynia lasted for a
      shorter period of time. These data suggest that a factor which is critically
      important for the maintenance of neuropathic pain develops between the 2nd and
      3rd postnatal weeks.

PMID- 8762003
TI  - Cellular mechanisms of adaptation of grafts to antibody.
AB  - New, more effective, strategies of immunosuppression, including those recently
      designed to induce durable T cell tolerance (by grafting allogeneic or xenogeneic
      haematopoietic cells into T lymphocyte-depleted recipients), leave humoral
      rejection as the main barrier to transplantation of vascularized organs between
      different species. Recent experimental work indicates that hyperacute rejection
      can be prevented by manipulations of antibodies and complement. In this paper, we
      review the mechanisms governing the interaction of antibodies with cell surface
      antigens in vitro and in vivo, and their cellular consequences. Evidence is
      presented that, in appropriate conditions, antibodies can protect by effecting
      modification of graft antigenicity (adaptation or accommodation).

PMID- 8762004
TI  - Antiepithelial cell antibodies do not impair paediatric renal allograft survival
      but appear to be associated with acute viral infections.
AB  - There is a reported association between antiepithelial cell (AEC) antibodies and
      increased renal allograft loss in paediatric recipients. Our unit experienced a
      dramatic fall in 1-year graft survival so we undertook a study to determine if
      AEC antibodies could account for such losses. We also studied healthy children
      and adults as well as a group of individuals with serologically proven viral
      infection in an attempt to determine the prevalence and possible aetiology of
      these antibodies. Sera were screened for AEC antibodies in a microcytotoxicity
      test using a lung epithelial cell line (A549) as target. The prevalence of these
      antibodies in our paediatric recipients was similar to that reported elsewhere
      but we found no correlation between the presence of AEC antibody and allograft
      loss. Within the control populations, we found the antibody was more prevalent in
      children than in adults (p < 0.0001). We also found a strong age banding pattern,
      with antibody being present in 50% of children under 10 years and declining with
      increasing age, so that by the age of 16 years the seroprevalence was similar to
      that found in our adults. However, AEC antibody had a significantly higher
      prevalence in individuals with active viral infection than in our healthy control
      groups (p = 0.00003). A positive association was noted between rubella and
      respiratory syncytial virus and AEC antibody presence and a negative association
      with varicella zoster. We conclude that AEC antibodies do not correlate with
      increased paediatric renal allograft loss but appear to be linked to certain
      viral infections.

PMID- 8762005
TI  - The functional consequences of partial calcineurin inhibition in human peripheral
      blood mononuclear leucocytes.
AB  - Calcium-dependent signal transduction is essential to the induction of cytokine
      expression by stimuli acting through the T cell receptor. In vitro, the
      immunosuppressant cyclosporine (CyA) blocks this pathway by inhibition of
      calcineurin (CN) phosphatase activity. But in vivo, patients on CyA have only 50%
      inhibition of CN and can mount cytokine responses. To simulate this state of
      partial inhibition, we studied the responses of human peripheral blood
      mononuclear leucocytes (PBL) in vitro at low CyA concentrations. PBL were
      challenged in vitro with calcium ionophores or anti-CD3 monoclonal antibody. The
      induction of IFN-gamma (interferon-gamma) and IL-2 (interleukin 2) steady-state
      mRNA was studied by Northern blotting and reverse transcriptase-polymerase chain
      reaction. IFN-gamma was assessed in a radiolabelled antibody binding assay or by
      ELISA (enzyme-linked immunosorbent assay). CN was assessed by dephosphorylation
      of a 32P-serine labelled 19 amino acid substrate. CyA inhibited CN with an IC50
      (concentration giving 50% inhibition) of 10 ng/ml (95% confidence interval, CI =
      8-13 ng/ml). Likewise, the induction of IFN-gamma and IL-2 mRNA by calcium
      ionophore A23187 was inhibited with IC50 of 14 ng/ml (95% CI = 8-27 ng/ml) and 32
      ng/ml (95% CI = 5-178 ng/ml), respectively, while the IC50 for inhibition of IFN
      gamma protein secretion was 8 ng/ml (95% CI = 9-18 ng/ml). Partial inhibition of
      CN also altered the threshold for IFN-gamma induction. CyA 10 ng/ml inhibited IFN
      gamma induction by anti-CD3 monoclonal antibody OKT3 significantly more at low
      OKT3 concentrations (10 ng/ml, mean +/- SEM = 72 +/- 9% inhibition) compared to
      high OKT3 concentrations (1000 ng/ml, 47 +/- 6%, p < 0.01). Similar results were
      seen using high and low concentrations of A23187. Finally, cells pretreated with
      CyA recovered the ability to respond to high concentrations of A23187 (5 microM)
      faster than low concentrations (0.5 microM). We conclude that the principal
      defect in lymphocytes with partial CN inhibition is a reduction in maximum
      cytokine output which is closely related to the degree of CN inhibition. In
      addition, there is significantly greater inhibition of weak stimuli compared to
      maximal stimuli. These defects may explain why patients on CyA can have a
      reduction in immune responsiveness but still retain protection from infection.

PMID- 8762006
TI  - Donor-specific transfusions enhance the immunosuppressive effects of single-dose
      cyclosporine A and CTLA4-Ig but do not result in long-term graft acceptance in a
      histoincompatible model of rat lung allograft rejection.

PMID- 8762007
TI  - Immunological and hemodynamic mechanisms in chronic renal allograft rejection.

PMID- 8762008
TI  - T cells from rejected human kidney allografts respond to heat shock protein 72.
AB  - The immune response to heat shock proteins (hsps) is gaining more and more
      interest. Members of the 65 and the 70 kDa hsp families have been shown to be
      target molecules of the immune system in autoimmune diseases, in cancer immunity
      and recently in the rejection of rat heart allografts. It was therefore the aim
      of the present study to investigate whether T cells propagated from two rejected
      human renal allografts also recognised hsps. In vivo activated interleukin-2 (IL
      2) receptor positive T cells were expanded from renal allografts, which had been
      removed because of irreversible rejection, by 1 week of culture in IL-2 only,
      followed by stimulation with OKT-3 in combination with IL-2. One T cell line was
      obtained from each graft. FACS analysis of the lines demonstrated that 51% and
      53% of the cells were CD4+ and 45% and 42% CD8+; 4% and 5% were gamma delta + T
      cells. Both lines had a significant proliferative response when stimulated with
      recombinant human hsp 72. In contrast, hsp 65 did not induce stimulation. The
      lines also showed a proliferative response upon stimulation with epithelial
      kidney cells, purified and cultured from the respective rejected kidneys. These
      results demonstrate that T cells propagated from rejected human kidney allografts
      recognize hsp 72. This suggests that hsp-specific T cells may play a role in the
      rejection process of allograft kidneys.

PMID- 8762009
TI  - Analysis of effector mechanisms in murine cardiac allograft rejection.
AB  - Multiple effector cells have been implicated in transplant rejection, including
      cytotoxic T cells, B cells, macrophages and NK cells. The purpose of this study
      was to examine the effector pathways which are critical to murine cardiac
      allograft rejection. RT-PCR (reverse transcriptase-polymerase chain reaction)
      analysis of syngeneic and allogeneic vascularized heterotopic cardiac grafts at
      5, 8 and 12 days following transplantation demonstrate constitutive expression of
      Fas in both the syngeneic and allogeneic grafts as well as in normal heart.
      However, FasL, granzyme, and perforin expression were shown to be up-regulated on
      days 5-12 in the allograft with no expression in syngeneic grafts or in normal
      hearts. We have recently analyzed the functional significance of T cell cytotoxic
      pathways and found that neither the Fas nor CD8+ cytotoxic pathways are required
      for murine cardiac allograft rejection. In light of these results, we
      investigated the functional significance of other effector cells in the rejection
      process. B cell deficient C57BL/10-IgHtm1Cgn mice rejected cardiac allografts
      from normal donors at control rate. Finally, RT-PCR was used to analyze the
      expression of macrophage effector transcripts in allograft rejection. Transcripts
      for iNOS (inducible nitric oxide synthase) and TNF alpha (tumor necrosis factor
      alpha) were up-regulated on days 5-12 in untreated allografts with undetectable
      expression in normal heart or syngeneic grafts. These results demonstrate that
      effective allograft rejection can occur in the absence of B cells and T cell
      cytotoxicity pathways suggesting that other effector pathways, such as delayed
      type hypersensitivity responses by macrophages, may be critical for allograft
      rejection.

PMID- 8762010
TI  - Role of donor-specific cytotoxic T cells in rejection of corneal allografts in
      normal and high-risk eyes.
AB  - Clinical ophthalmologists are highly successful in grafting allogeneic corneas
      onto healthy eye graft beds--only a small percentage are rejected. By contrast, a
      high percentage of allografts are rejected when grafted into vascularized or
      '"high-risk' recipient eyes. The following experiments test the hypothesis that
      donor-specific cytotoxic T cells mediate graft rejection in high-risk, but not
      normal, eyes. MHC plus minor histoincompatible C57BL/6 corneas were grafted
      orthotopically onto BALB/c mice. Healthy recipient eyes were trephined and served
      as normal graft beds; corneal vascularization was induced by penetrating sutures
      and these eyes served as 'high-risk' graft beds. Cytotoxic T cells were assayed
      at 2 and 8 weeks postgrafting using either draining cervical lymph nodes or
      spleen cells restimulated for 3 days with irradiated allogeneic splenic
      stimulator cells. As a positive control, donor-specific cytotoxic T cells were
      induced in mice immunized by subcutaneous injection of allogeneic spleen cells. A
      low percentage (only 50%) of corneal allografts were rejected when placed
      orthotopically onto normal healthy eyes. Donor-specific cytotoxic cells were not
      detected in the draining lymph nodes or spleens of mice that either accepted, or
      rejected their corneal graft. The failure to detect cytotoxic T cells was not due
      to anergy or the deletion of allospecific precursors of cytotoxic T cells. By
      contrast, 97% of corneal allografts were rejected from high-risk recipient eyes
      (no immune privilege). Donor-specific cytotoxic T cells were routinely detected
      in the draining lymph nodes of these mice and their appearance coincided with
      graft rejection. We conclude that allografts placed onto normal healthy eyes fail
      to induce donor-specific cytotoxic T cells. In the absence of specific cytotoxic
      T cells, other alloimmune effectors are less successful at mediating rejection.
      By contrast, allografts placed onto high-risk eyes induce donor-specific
      cytotoxic T cells, and all grafts are universally rejected. These results imply
      that immune privilege can protect corneal allografts from most effector
      mechanisms, except cytotoxic T cells.

PMID- 8762011
TI  - Minor H, rather than MHC, alloantigens offer the greater barrier to successful
      orthotopic corneal transplantation in mice.
AB  - Irrespective of HLA matching, a far higher proportion of human corneal allografts
      placed orthotopically in avascular corneal graft beds are accepted indefinitely,
      compared to other types of solid tissue allografts. However, many more corneal
      grafts are rejected if they are transplanted onto neovascularized recipient eyes.
      Using a murine model of orthotopic corneal transplantation in which grafts were
      placed in normal eyes, we have reported previously that grafts bearing minor H
      antigens alone are more likely to be rejected (approximately 50%) than are grafts
      displaying only MHC alloantigens (< 20%). Moreover, recipients of MHC plus minor
      H incompatible corneal grafts developed delayed hypersensitivity (DH) directed
      solely at minor H antigens. These studies have now been extended to include
      corneal grafts placed in neovascularized recipient eyes. Neovascularization was
      induced by placing sutures in the central cornea of one eye of BALB/c mice. Two
      weeks later corneas from C57BL/10 donors were grafted into these eyes. Rejection
      reactions were first apparent within 7 days and all grafts were destroyed by 14
      days. Donor-specific DH responses were examined by injecting irradiated donor
      antigen-bearing spleen cells into the ear pinna. To distinguish DH directed at
      MHC versus minor antigens, some graft recipients were ear-challenged with BALB.B
      cells (donor MHC only), while other received B10.D2 cells (donor minor H only).
      Intense ear-swelling responses were evoked by B10.D2 cells, but not by BALB.B
      cells. These findings indicate that, for orthotopic corneal allografts, minor H
      antigens offer a more formidable barrier to graft acceptance than do MHC-encoded
      antigens. We speculate that this unexpected outcome may reflect a reduced level
      of MHC expression on corneal tissue. Moreover since the cornea lacks bone marrow
      derived dendritic cells, allorecognition by recipient T cells must occur via the
      indirect pathway, and in this situation minor H antigens may compete favorably
      with MHC antigens for processing and presentation by recipient antigen-presenting
      cells.

PMID- 8762012
TI  - Adhesion molecules and activation markers in acute rejection of human renal
      allografts.

PMID- 8762013
TI  - Increased expression of adhesion molecules in liver allografts during
      cytomegalovirus infection.

PMID- 8762014
TI  - CD45RA+ and CD45RO+ T cells differ in susceptibility to cyclosporin A mediated
      inhibition of interleukin-2 production.
AB  - Lymphocytes in different states of activation use different intracellular
      signalling pathways and may therefore differ in their susceptibility to
      immunosuppressive agents. In this study we examined the proliferation and
      production of interleukin-2 (IL-2) by unprimed/naive CD4+CD45RA+ T cells and
      previously activated/memory CD4+CD45RO+ T cells from human peripheral blood when
      stimulated in vitro in the presence of cyclosporin A (CsA). Further, the
      dependency of the IL-2 response on calcium (Ca2+) ions was analysed by the
      addition of the chelating agent EGTA. The CD4+CD45RO+ memory T cells were shown
      to be less susceptible to CsA and less dependent on the level of Ca+ ions than
      the naive CD4+CD45RA+ T cells. The subcellular mechanisms involved in this
      difference and the potential clinical implications are discussed.

PMID- 8762015
TI  - Mycophenolate mofetil inhibits lymphocyte binding and the upregulation of
      adhesion molecules in acute rejection of rat kidney allografts.
AB  - Mycophenolate mofetil (MMF) interacts with purine metabolism and possibly with
      the expression of adhesion molecules. In the present study, we analysed the
      expression of these molecules in transplanted kidney allografts treated with RS
      LBNF1 kidneys were orthotopically transplanted into Lewis rats and either treated
      with RS (20 mg/kg/day) or vehicle. Rats were harvested 3, 5 and 7 days following
      transplantation. For binding studies, fresh-frozen sections of transplanted
      kidneys were incubated with lymph node lymphocytes (LNL) derived from
      transplanted rats. Additionally, immunohistology was performed with various
      monoclonal antibodies. In general, MMF resulted in better preservation of graft
      structure by 7 days. Cellular infiltration and tubular atrophy were less
      pronounced. At day 3, macrophages were diminished in MMF-treated animals to a
      high extent, while the number of T cells was almost identical to that of
      controls. In addition, the number of cells positive for MHC class II and LFA-1
      was reduced in the MMF-treated animals. These findings correlated with the
      binding results. Three days following engraftment, LNL bound to MMF-treated
      kidneys to a lesser extent compared to controls. In conclusion, MMF resulted in a
      markedly reduced leucocytic infiltrate, presumably based on a reduced expression
      of lymphocytic adhesion molecules and an interaction with macrophages.

PMID- 8762016
TI  - Diltiazem minimizes tubular damage due to FK506-mediated nephrotoxicity following
      ischemia and reperfusion in rats.
AB  - We examined the nephrotoxicity of tacrolimus (FK506) in a model of mild warm
      ischemia. After clamping of both renal arteries of male Sprague-Dawley rats for
      20 min, the animals received tacrolimus (3 mg/kg/day i.p.), vehicle of a
      combination of tacrolimus (3 mg/kg/day i.p.) and diltiazem (12 mg/kg, orally) or
      vehicle and diltiazem (12 mg/kg, orally). The excretion of urinary enzymes was
      determined on a daily basis, creatinine clearance at day 10. Tacrolimus
      significantly increased NAG (N-acetyl-beta-glucosaminidase) excretion and
      associated histological damage, finally decreasing creatinine clearance. The
      toxic potential of tacrolimus was markedly enhanced by ischemia. The additional
      application of diltiazem reduced NAG excretion and histological damage without
      affecting creatinine clearance. Thus, the protective effect of diltiazem on
      tacrolimus-induced nephrotoxicity seems to be at least partially a tubular one.

PMID- 8762017
TI  - Allograft immune response with sCR1 intervention.
AB  - The deposition of complement (C) components on tissues of transplanted organs may
      induce many proinflammatory responses. The role of such C activation in allograft
      rejection is uncertain. We addressed this question by inhibiting C at the level
      of the C3 and C5 convertases, preventing C activation and progression of its
      cascade, using recombinant human soluble complement receptor 1 (sCR1) in an
      unsensitized rat renal allograft model. Fully MHC disparate Lewis to DA rat renal
      allograft recipients given 25 mg/kg sCR1 daily, with saline-treated allograft
      recipients as controls (n = 15 in each group), were sacrificed from day 1 to day
      5 post-transplant, and examined histopathologically, and for the deposition of C3
      and C5b-9 membrane attack complex (MAC), and for the presence of leucocyte
      antigen markers. Treated animals demonstrated a reduction in vascular injury and
      cellular infiltration, coincident with reduced C deposition. Flow cytometric
      analysis of leucocyte subpopulations in the spleen showed a reduction in
      activated (CD25 positive) B and T cells in treated animals, compared to saline
      treated controls. The results suggest that C inhibition with sCR1, in an
      unsensitized model of allograft rejection, was able to suppress the vascular and
      cell mediated components of tissue injury. The data support not only a role for C
      in antibody and possibly cell mediated cytotoxicity in the graft, but also
      suggest a role in the primary immune response leading to both T cell and B cell
      activation.

PMID- 8762018
TI  - MHC class II tolerant T cells undergo apoptosis upon re-exposure to tolerogen in
      vivo.
AB  - Tolerance of MHC class II alloantigens can be achieved by intravenous injection
      of semiallogeneic hematopoietic cells into neonatal mice. Lymphoid cells of
      tolerant mice fail to proliferate or secrete interleukins IL-2 or IL-4 when
      stimulated in vitro with tolerogen. Since the lymphoid organs of B10.T(6R)
      tolerant mice contain normal levels of I-E reactive (V beta 11+) CD4+ T cells,
      deletion of alloreactive T cells does not appear to be the mechanism involved in
      the tolerance induction. To test whether T cells from tolerant animals can become
      activated under conditions that do not involve alloantigen stimulation, we
      stimulated these cells with immobilized anti-V beta 11 antibodies. Spleen cells
      from grafted tolerant and rejector mice proliferated in response to anti-V beta
      11+ antibodies, suggesting they were not inert. We then tested whether V beta 11+
      T cells from grafted mice can be induced to proliferate following stimulation
      with alloantigen in vivo. We adoptively transferred T cells from grafted tolerant
      and rejector mice into irradiated (B10.AQR x B10.T(6R))F1 mice and harvested the
      lymphoid organs after 65 h. Cells from both grafted tolerant and rejector mice
      underwent blast transformation, but only cells from rejector mice proliferated
      when exposed to immobilized anti-V beta 11 antibodies. The failure of V beta 11+
      cells from tolerant mice to proliferate after in vivo stimulation may be because
      they are apoptotic. To test this hypothesis, spleen cells from naive or
      neonatally tolerized (with (B10.AQR x B10.T(6R))F1 cells) B10.T(6R) mice were
      adoptively transferred into irradiated (B10.AQR x B10.T(6R))F1 mice and bcl-2
      expression was analysed in harvested V beta 11+ cells. Large cells recovered from
      recipients of naive 6R cells expressed bcl-2 mRNA. By contrast, large cells
      harvested from recipients of tolerized 6R cells did not express bcl-2 mRNA,
      suggesting bcl-2 mRNA expression was downregulated in these mice. Moreover, in
      another experiment, large V beta 11+ cells from grafted tolerant animals
      recovered after transfer into irradiated (B10.AQR x B10.T(6R))F1 mice did not
      express the bcl-2 protein as determined by flow cytometry, and contained
      fragmented DNA as assessed by the TUNEL method. Taken together, these data
      suggest that MHC class II tolerant T cells undergo apoptosis upon re-exposure to
      tolerogen in vivo.

PMID- 8762019
TI  - Prolonged islet allograft acceptance in the absence of interleukin 4 expression.
AB  - Murine CTLA4/Fc therapy leads to permanent engraftment of islet allografts in
      interleukin 4 (IL-4) knockout (IL-4-/- mice. Interestingly, IL-4+/- hosts were
      more resistant to tolerance induction than IL-4-/- mice. An IL-2/Fc fusion
      protein abrogates the effect of CTLA4/Fc therapy while an IL-4/Fc fusion protein
      tends to inhibit rather than enhance the effect of CTLA/Fc treatment in IL-4-/-
      recipients. We conclude that allograft acceptance requires principally a blockade
      of T cell activation rather than 'immune deviation' of the T cell activation
      program to Th2 cytokines (i.e. IL-4).

PMID- 8762020
TI  - Long-term engraftment of precultured post-5-fluorouracil allogeneic marrow in
      mice conditioned with a nonmyeloablative regimen: relevance for a gene therapy
      approach to tolerance induction.
AB  - Introduction of MHC class I Kb cDNA via recombinant retrovirus into B10.AKM (Kk)
      bone marrow cells (BMC) has been shown to confer specific hyporesponsiveness to
      B10.MBR (Kb) allogeneic skin grafts in lethally irradiated B10.AKM recipients of
      the transduced syngeneic BMC. We have recently developed a nonmyeloablative
      conditioning regimen that allows engraftment of fully MHC-mismatched allogeneic
      bone marrow and the induction of donor-specific tolerance. We ultimately plan to
      adapt this nonmyeloablative regimen for the use of retroviral transfer of the Kb
      gene to syngeneic marrow. As a step toward this goal, we have assessed the
      effects of our current BMC transduction protocol on engraftment of class I
      mismatched marrow in mice prepared using the nonmyeloablative regimen. BMC from
      B10.MBR (KbIkDq) mice treated 2 days earlier with 5-fluorouracil (5-FU) were
      cultured for 4 days with rIL-3 and rIL-6, and then injected into B10.AKM (KkIkDq)
      recipients conditioned with anti-CD4 and anti-CD8 mAbs, 7 Gy of thymic
      irradiation and 3 Gy of whole body irradiation. Engraftment was comparable to
      that of freshly prepared normal B10.MBR marrow. All recipients of 10(6)
      precultured BMC developed long-term multilineage mixed WBC (white blood cells)
      chimerism, and six of seven of these animals showed long-term specific tolerance
      to B10.MBR skin grafts. Four of seven recipients of 2 x 10(5) precultured BMC
      showed long-term repopulation by the donor of > 1% of multiple WBC lineages and
      four of five recipients showed specific tolerance to B10.MBR tail skin. These
      data suggest that our previously described nonmyeloablative conditioning regimen
      could be applicable to the gene therapy approach for the induction of donor
      specific transplantation tolerance.

PMID- 8762021
TI  - The in vivo quantification of myocardial performance in rabbits: a model for
      evaluation of cardiac gene therapy.
AB  - Evaluating cardiac gene therapy in the intact animal requires an index of cardiac
      function capable of detecting regional differences in contractility in a load
      independent fashion. Potentially load-insensitive measures of ventricular
      performance were therefore evaluated in 10 open- and closed-chested, anesthetized
      rabbits. LV transmural pressure and myocardial segment length were measured using
      micromanometry and sonomicrometry during steady-state and transient inferior vena
      caval occlusion, over a range of inotropic and loading conditions. For each
      intervention, segmental stroke work was calculated as the area within the left
      ventricular transmural pressure-length loops at a given end-diastolic segment
      length during inferior vena caval occlusion; regression analysis was applied to
      obtain the linear Frank-Starling relationship. In both open- and closed-chested
      states, these relationships were highly linear (r = 0.97 +/- 0.1) and
      reproducible. The slope of the linear relationship between segmental stroke work
      and end-diastolic segment length increased significantly with calcium and
      epinephrine infusions (P < 0.05 v control) but was not significantly altered by
      decreased afterload or increased afterload (P > 0.4). The x-intercept was not
      significantly altered by changes in intropy or afterload (P > 0.4). These data
      validate the linear Frank-Starling relationship and the slope, MW, as a load
      insensitive index of contractility in the intact rabbit. This study presents a
      novel approach to the quantification of regional cardiac function in smaller
      animals.

PMID- 8762022
TI  - Regulation of fatty acid oxidation by acetyl-CoA generated from glucose
      utilization in isolated myocytes.
AB  - The regulation of fatty acid oxidation in isolated myocytes was examined by
      manipulating mitochondrial acetyl-CoA levels produced by carbohydrate and fatty
      acid oxidation. L-carnitine had no effect on the oxidation of [U-14C]glucose, but
      stimulated oxidation of [1-14C]palmitate in a concentration-dependent manner. L
      carnitine (5 mM) increased palmitate oxidation by 37%. The phosphodiesterase
      inhibitor, enoximone (250 microM), also increased palmitate oxidation by 51%.
      Addition of L-carnitine to enoximone resulted in a two-fold increase of palmitate
      oxidation. Whereas, dichloroacetate (DCA, 1 mM), which stimulates PDH activity,
      decreased palmitate oxidation by 25%. Furthermore, the addition of DCA to
      myocytes preincubated with either L-carnitine or enoximone, had no effect on the
      carnitine-induced stimulation of palmitate, and reduced that of enoximone by 50%.
      Varied concentrations of DCA decreased the oxidation of palmitate and octanoate;
      but increased glucose oxidation in myocytes. The rate of efflux of
      acetylcarnitine was highest when pyruvate was present in the medium compared to
      efflux rates in presence of palmitate or palmitate plus glucose. Although the
      addition of L-carnitine plus enoximone resulted in a two-fold increase in
      palmitate oxidation, acetylcarnitine efflux was minimal under these conditions.
      Acetylcarnitine efflux was highest when pyruvate was present in the medium. These
      rates were dramatically decreased when myocytes were preincubated with enoximone,
      despite the stimulation of palmitate oxidation by this compound. These data
      suggest that: (1) fatty acid oxidation is influenced by acetyl-CoA produced from
      pyruvate metabolism; (2) L-carnitine may be specific for mitochondrial acetyl-CoA
      derived from pyruvate oxidation; and (3) it is probable that acetyl-CoA from beta
      oxidation of fatty acids is directly channeled into the citric acid cycle.

PMID- 8762023
TI  - The role of hsp70 and IP3-DAG mechanism in the adaptive stabilization of
      structures and heart protection.
AB  - This study has shown that the maximal activation of the IP3-DAG regulatory
      circuit is observed on the 14th day of adaptation to repeated stresses. This
      activation is characterized by increased activity of phospholipase C and of the
      positive inotropic response of isolated heart to an alpha-agonist.
      Simultaneously, this activation is accompanied by the accumulation of five heat
      shock protein 70 (hsp70) isoforms. The IP3-DAG circuit activation and the hsp70
      accumulation are accompanied by a significant increase in the cardiac resistance
      to post-ischemic reperfusion, as evidenced by a considerable decrease in the
      contracture, arrhythmias and the creatine kinase release into the perfusate.
      Continuation of the adaptation to repeated stresses for 28 days leads to complete
      reversal of the observed shifts.

PMID- 8762024
TI  - Inhibitory effects of O-benzyl-phosphocreatine ethyl ester in rabbit myocardium.
AB  - O-benzyl-phosphocreatine ethyl ester (BPC-EE) applied in superfusion evoked a
      negative chronotropic effect in the sinus node strips. The drug reduced the
      action potential amplitude and duration, decreased the resting potential, and
      diminished the isometric tension in the atrial trabeculae and papillary muscles.
      BPC-EE acted in a dose-dependent manner, and at 2.5 mmol/l it abolished the
      electrical phenomena in the examined preparations. BPC-EE lowered also the ATP
      and phosphocreatine content and decreased the creation kinase activity in
      ventricular specimens. The last finding is probably responsible for the remaining
      effects of BPC-EE.

PMID- 8762025
TI  - Angiotensin converting enzyme and myofibroblasts during tissue repair in the rat
      heart.
AB  - Following left coronary artery ligation in the rat, markedly increased
      angiotensin converting enzyme (ACE) binding appears at the site of myocardial
      infarction (MI). This is also the case in fibrosed visceral pericardium that
      follows pericardiotomy alone (without MI). Immunohistochemical ACE labeling,
      using a monoclonal antibody, indicates fibroblast-like calls express ACE at each
      of these sites of tissue repair. It is unknown, however, whether these cells are
      phenotypically transformed fibroblasts containing alpha-smooth muscle actin (i.e.
      myofibroblasts). This study was therefore undertaken to determine whether
      myofibroblasts appear at the site of MI and pericardial fibrosis and their
      relationship to ACE expression. MI was created by left coronary artery ligation.
      Fibrosis of the visceral pericardium was induced by pericardiotomy alone. Hearts
      were studied on postoperative day 3, week 1, 2, 4 and 8. In serial sections of
      the same heart: immunohistochemistry (anti alpha-smooth muscle actin antibody and
      monoclonal ACE antibody, 9B9) was used to detect myofibroblasts and cells
      expressing ACE, respectively. We found that at sites of MI and pericardial
      fibrosis, myofibroblasts began to appear on day 3 and became abundant at week 1,
      2, 4 and remained in these repairing sites for at least 8 weeks. Myofibroblasts
      at sites of MI and pericardial fibrosis are positively labeled by ACE antibody.
      Thus in these models of tissue repair involving either MI or pericardial
      fibrosis, myofibroblasts are associated with ACE expression. These findings
      suggest that myofibroblast ACE may play a role in the fibrogenic response of
      tissue repair in the rat myocardium by regulating local concentrations of
      substances involved in healing and matrix remodeling.

PMID- 8762026
TI  - Endocardial endothelium and myocardial performance in rats: effects of changing
      extracellular calcium and phenylephrine.
AB  - It is known that endocardial endothelium (EE) modulates the performance of its
      subjacent myocardium. However, one species where these effects have been more
      difficult to describe is the rat. As the rat is a species which is used to
      evaluate the contractile effects of various pathologic conditions, a better
      appreciation of the contractile effects of EE and its modulatory role on the
      contractile effects of inotropic substances is important. In this study, the
      contractile effects of increasing extracellular calcium concentrations (0.7 mM to
      3.25 mM) and phenylephrine (10(-7) to 10(-4) M) on rat papillary muscles with
      intact endocardial endothelium (EE on) and after endocardial endothelial removal
      (EE off) were assessed. At 0.7 mM extracellular calcium concentration,
      endocardial endothelial removal decreased all measured indices of myocardial
      performance (P < 0.05 EE on v EE off), except for maximum rate of unloaded muscle
      shortening (Vmax) which did not change, and decreased time to peak tension
      development (TTPT) as well as shortening of time to half tension decline from
      peak tension (RT1/2) shortening. Increasing extracellular calcium concentration
      from 0.7 mM to 3.25 mM caused all indices of myocardial performance and RT1/2 to
      increase more in muscles without EE, such that at 2.5 mM extracellular calcium
      all differences between EE on and EE off had disappeared. The only exception was
      TTPT which decreased with increasing extracellular calcium concentrations in
      muscles with EE on but increased in muscles with EE off. Again, at 2.5 mM
      extracellular calcium concentration differences in TTPT between EE on and EE off
      had disappeared. Except for minor differences on TTPT, increasing phenylephrine
      concentrations had similar contractile effects on muscles with EE on and EE off.
      These results indicate that EE modulates rat myocardial contraction and that
      these effects are best observed at lower extracellular calcium concentrations
      (0.7 mM). They also indicate that EE does not appear to significantly modulate
      the myocardial effects of alpha-adrenergic agonists in the rat.

PMID- 8762027
TI  - Effect of ischemic preconditioning and PKC activation on acidification during
      ischemia in rat heart.
AB  - Ischemic preconditioning (PC) has been shown to attenuate intracellular
      acidification during a subsequent period of ischemia, to minimize stunning, and
      to decrease infarct size, PKC activation has been suggested to be involved in
      this phenomenon. The present study is designed to test whether PKC activation
      could mimic and PKC inhibition could block the PC effects on intracellular
      acidification during ischemia and on stunning during reflow in Langendorff
      perfused rat hearts. Prior to 20 min of sustained global normothermic ischemia,
      groups of hearts were treated with the PKC activators 4 beta-phorbol 12-myristate
      13-acetate (PMA) or 1,2-dioctanoyl-srt-glycerol (DOG), a group of hearts was
      treated with the PKC inhibitor chelerythrine (CH), a group was treated with DOG
      plus CH, a group was preconditioned with four cycles of 5 min of ischemia and 5
      min of reflow, and a group was treated with CH during PC. Recovery of left
      ventricular developed pressure (% of initial, pretreatment, preischemic LVDP),
      measured after 20 min of reflow, was improved in hearts treated with DOG, but not
      PMA (80 +/- 3% (DOG), 55 +/- 3% (PMA) v 51 +/- 3% (control), P < 0.05 between DOG
      and control), although both caused a similar degree of PKC translocation
      (measured by fractionation followed by an assay of PKC activity using
      incorporation of 32P into histone). The improved recovery of LVDP in the PC group
      and in the DOG group was blocked by chelerythrine. Measurement of pH (by 31P NMR)
      showed that DOG reduced acidification at 15-20 min of ischemia, although the
      effect was not as great as PC, while PMA did not reduce acidification. The effect
      of DOG on pHi was attenuated by CH; however, the PC-induced attenuation of the
      fall in pHi, was not affected by CH. High energy phosphates (measured by 31P NMR)
      were not significantly different between any of the groups during ischemia or
      reflow. This study confirms that the protective effect of ischemic
      preconditioning on stunning in rat heart can be eliminated by inhibition of PKC,
      but suggests that the effect of PC on the fall in pHi during sustained ischemia
      is not mediated by PKC.

PMID- 8762028
TI  - Vascular-derived myocardial contractile factor: positive myocardial inotropic
      substance released from medial layer of the canine aorta.
AB  - Interactions between the various cell types that make up the cardiovascular
      system are known to play an important role in maintaining homeostasis. One area
      about smooth muscle cells that has received little attention, despite the
      production of a wide variety of mediators by smooth muscle cells, is their effect
      on myocardial function. In this study, the myocardial contractile effects of four
      different types of dog aortic strips on rabbit papillary muscles were evaluated.
      Of these, medial vascular smooth muscle strips most consistently (65% of the
      time) produced a "vascular-derived contractile factor" (VDCF), which caused a 15%
      increase in isometric twitch tension and a 24% increase in isotonic twitch
      shortening with no change in twitch configuration. Endovascular strips with or
      without intact endothelium and complete aortic rings had less consistent effects.
      Vascular-derived contractile factor was stable after freezing at -80 degrees C,
      its activity was not modified by a broad spectrum peptidase, but it was heat
      labile. The angiotensin II blocker, losartan, did not modify its effects.
      However, incubation with indomethacin did reduce, but did not eliminate, the
      contractile effects of vascular strips. The addition of alpha 1- and beta
      blockers did not further modify the effects of VDCF. Endocardial endothelial
      removal increased the effects of VDCF. No correlation existed between endothelin
      levels and the contractile effects of vascular strips. It is concluded that VDCF
      is produced by the medial layer of large vessels but its exact cellular origin is
      uncertain. These findings expand the ever-increasing understanding of the inter
      relationship between the structures that make up the cardiovascular system, and
      open the door to new studies evaluating the inter-relationship of vessels and
      myocardium.

PMID- 8762029
TI  - Comparison of the effects of class I anti-arrhythmic drugs, cibenzoline,
      mexiletine and flecainide, on the delayed rectifier K+ current of guinea-pig
      ventricular myocytes.
AB  - The effect of class I anti-arrhythmic drugs, cibenzoline, mexiletine and
      flecainide, on the delayed rectifier potassium current (IK) in guinea-pig
      ventricular myocytes was studied using whole cell voltage clamp techniques and
      under blockade of the L-type calcium current by 5 microM nitrendipine. IK
      consisted of two different current systems, as reported by Sanguinetti and
      Jurkiewicz (1990), i.e. an E4031-sensitive rapidly activating component (IKr)
      with a strong inward-going rectification property and an E4031-insensitive slowly
      activating component (IKs) with little rectification. Cibenzoline (30 microM)
      decreased both IKr and IKs while flecainide (10 and 30 microM) decreased the IKr
      exclusively. Mexiletine (30 microM), in contrast, affected neither IKr nor IKs.
      Since the inhibition of IK(r) and/or IKs prolongs duration of action potentials
      and refractory periods, class I drugs which also possess the class III effect may
      have additional effects in treating certain re-entrant arrhythmias.

PMID- 8762030
TI  - Pyruvate dehydrogenase activity and malonyl CoA levels in normal and ischemic
      swine myocardium: effects of dichloroacetate.
AB  - The purposes of this study were to: (1) assess myocardial pyruvate dehydrogenase
      (PDH) activity and substrate exchange under well-perfused and ischemic
      conditions; (2) determine the metabolic effects of an intra-coronary infusion of
      the PDH activator, dichloroacetate (DCA); and (3) measure the effects of ischemia
      and DCA on malonyl CoA levels. Experiments were performed in anesthetised open
      chest swine under non-ischemic conditions, followed by 40 min with a 60%
      reduction in left anterior descending coronary artery (LAD) blood flow.
      Myocardial needle biopsies for measurement of PDH activity were taken after an
      intracoronary infusion of either saline or DCA (1 mM in LAD blood) under aerobic
      conditions, and after 37 min of ischemia. Pyruvate dehydrogenase activity was
      measured with and without maximal activation by swine PDH phosphatase. Malonyl
      CoA and acetyl CoA were measured after 40 min of LAD ischemia in myocardium from
      the ischemic DCA- or saline-treated LAD bed, and the non-ischemic untreated left
      circumflex coronary artery (CFX) perfusion bed. Net glucose, lactate and free
      fatty acid (FFA) uptakes were measured across the LAD perfusion bed throughout
      the study. Dichloroacetate treatment increased the amount of active
      dephosphorylated PDH to 88% of the total activity under aerobic conditions,
      compared to 55% with saline (P < 0.01). Ischemia did not significantly change PDH
      activation state in either group. Acetyl CoA and malonyl CoA contents were
      significantly elevated in ischemic DCA-treated myocardium compared to saline
      treated ischemic myocardium. Dichloroacetate treatment significantly lowered
      rates of myocardial FFA uptake under both aerobic and ischemic conditions, but
      did not effect glucose uptake or lactate exchange. Free fatty acid uptake was
      negatively correlated to malonyl CoA levels (r = -0.68) during ischemia. It is
      proposed that the inhibition of FFA uptake observed with DCA in ischemic
      myocardium is due to malonyl CoA inhibition of carnitine palmitoyl transferase I.

PMID- 8762031
TI  - A cardiac muscle model relating sarcomere dynamics to calcium kinetics.
AB  - A muscle model establishing the link between cross-bridge dynamics and
      intracellular Ca2+ kinetics was assessed by simulation of experiments performed
      in isolated cardiac muscle. The model is composed by the series arrangement of
      muscle units formed by inextensible thick and thin filaments in parallel with an
      elastic element. Attached cross-bridges act as independent force generators whose
      force is linearly related to the elongation of their elastic structure. Ca2+
      kinetics is described by a four-state system of sites on the thin filament
      associated with troponin C: sites with free troponin C (T), sites with Ca2+ bound
      to troponin C (TCa); sites with Ca2+ bound to troponin C and attached cross
      bridges (TCa*); and sites with troponin C not associated with Ca2+ and attached
      cross-bridges (T*). The intracellular Ca2+ concentration ([Ca2+]) is controlled
      solely by the sarcoplasmic reticulum through an inflow function and a saturated
      outflow pump function. All the simulations were performed using the same set of
      parameters. The model was able to reproduce the following experiments in cardiac
      muscle: (a) time course of isometric force (peak force: 46.5 mN/mm2),
      intracellular [Ca2+] (peak [Ca2+]: 1.5 microM); (b) force-length-[Ca2+]
      relations; (c) transient response of force to step changes in length; (d) force
      velocity relation (maximum velocity: 3 microns/s); (e) the force response to
      length pulses to estimate the time course of [TCa]; (f) force response to quick
      releases showing the superactivating and deactivating effects of shortening; (g)
      stiffness response to sinusoidal length changes; and (h) time course of active
      state. The good accordance of the simulations with experimental results indicates
      that the model is an adequate representation of the link between cross-bridge
      dynamic behaviour and Ca2+ kinetics.

PMID- 8762032
TI  - Cardioprotective actions of verapamil on the beta-adrenergic receptor complex in
      acute canine Chagas' disease.
AB  - The effect of verapamil treatment on the myocardial beta-adrenergic adenylyl
      cyclase complex in acute canine Chagas' disease was investigated. Relative to
      uninfected animals, 30 days of infection with T. cruzi reduced myocardial
      adenylyl cyclase activity by over 75%. With continuous verapamil treatment, the
      infection-associated reduction in adenylyl cyclase activity was less than 50%.
      The individual components of the beta-adrenergic receptor complex were
      characterized. INFECTION: (1) increased right ventricular (RV) beta-adrenergic
      receptor (beta AR) density five-fold; (2) decreased left ventricle beta AR
      density by 20%; (3) reduced the proportion of high-affinity beta AR receptors to
      the same extent in both left and right ventricles; (4) reduced alpha s by 50% as
      determined by Western blot analysis, increased alpha 11-3 but did not change
      alpha 0; and (5) decreased the magnitude of pertussis-toxin-dependent [32P]ADP
      ribosylation by 60% as well as the proportion of [32P]ADP-ribose incorporated in
      alpha 0. Verapamil treatment of infected animals restored RV beta AR receptor
      density, alpha s and alpha i1-3 to control levels but had no influence on any
      aspect of pertussis-toxin-dependent [32P]ADP-ribosylation. Verapamil treatment of
      uninfected animals also: (1) increased beta-adrenergic adenylyl cyclase activity;
      (2) increased beta AR density in the RV but not the LV; (3) reduced high- to low
      affinity beta-adrenergic receptors; and (4) affected only alpha i2 (50%
      decrease). The results indicate that the major actions of verapamil on the beta
      adrenergic adenylyl cyclase complex in acute canine Chagas' disease may help to
      account for its cardioprotective effects.

PMID- 8762034
TI  - Unitary current through the inward rectifier K+ channel cloned from rabbit heart-
      comparison with the native K+ channel.
AB  - Recently, we have cloned a cDNA for a putative cardiac inward rectifier K+
      channel (RBHIK1) from rabbit cardiac muscles. However, it's single channel
      characteristics have remained unknown. Therefore, we investigated the single
      channel characteristics of the RBHIK1 channel expressed in Xenopus oocytes by the
      cell attached patch clamp configuration, and compared them with those of the
      native Ik1 channel of the freshly-isolated ventricular myocytes under similar
      temperature conditions. In patch clamp experiments with 145 mmol/l K+ in the
      pipette at room temperature (20-22 degrees C), both the RBHIK1 currents and the
      native Ik1 showed a strong inward rectifying property. The single channel
      conductance of the RBHIK1 channel was 17.8 +/- 0.47 pS (n = 4), and that of the
      native Ik1 channel was 23.5 +/- 0.29 pS (n = 5). The activities of the cloned
      channel were sensitive to the putative K+ channel blockers (TEA, Cs+ and Ba2+).
      The open and closed time histograms at -140 mV could be fitted by a single
      exponential both in the RBHIK1 channel and the native Ik1 channel. Although the
      closed-time histogram of the native Ik1 channel was fitted by a sum of two
      exponential curves, that of the RBHIK1 channel was fitted by a single exponential
      curve. The sublevel corresponding to two-thirds of the unitary current was
      observed both in the RBHIK1 channel and the native Ik1, but it was more
      frequently detected in the RBHIK1 channel. Amplitude histogram constructed at 
      140mV in the RBHIK1 channel exhibited three peaks, which indicated closed, full
      open, and 2/3 sublevel state, respectively. Unitary current was calculated to be
      2.5 pA and sublevel of the unitary current was 1.68 pA. These characterization in
      the single channel activities of the RBHIK1 channel will help to study the
      molecular regulation of the Ik1 channel in cardiac cells.

PMID- 8762033
TI  - Ryanodine perfusion decreases cardiac mechanical function without affecting
      homogenate sarcoplasmic reticulum Ca2+ uptake: comparison with the stunned heart.
AB  - This study tested the hypothesis that perfusion with low concentrations of
      ryanodine, which opens the sarcoplasmic reticulum (SR) Ca2+ channel in a sub
      conducting state, could mimic the effects of stunning on both mechanical and SR
      activity. Perfusion of isolated rat hearts with 10-160 nM ryanodine progressively
      decreased left ventricular developed pressure (LVDP) and increased end-diastolic
      pressure (EDP), but LVDP decreased more and EDP increased less than in the
      stunned heart. The effect of ryanodine perfusion on LVDP and EDP is consistent
      with the opening of the SR Ca2+ channel by high-affinity ryanodine binding,
      reducing SR Ca2+ content and interfering with mechanical function. In contrast to
      stunning, ryanodine perfusion did not affect the homogenate Ca2+ uptake rates
      measured in the presence or absence of high [ryanodine]. Perfusion with 80 nM 3H
      ryanodine resulted in a large decline in LVDP, but only a small degree of
      ryanodine binding. Thus, prolonged opening of only a few channels affects the SR
      in situ, whereas this is undetectable in the homogenate. Higher levels of
      ryanodine binding (0.3 pmol/mg) to the in vitro homogenate also did not affect
      the homogenate Ca(2+)-uptake rate in the presence or absence of high [ryanodine],
      whereas it reduced the stimulation of Ca2+ uptake by ruthenium red. High-affinity
      ryanodine binding to the SR Ca2+ channel, either by perfusion or by binding after
      homogenisation, did not duplicate the increased Ca2+ efflux observed in the
      stunned heart, suggesting that the SR defect in the stunned heart is not a
      prolonged opening of a sub-conducting state of the SR Ca2+ channel.

PMID- 8762035
TI  - Effects of exogenous neuropeptide Y on automaticity of isolated Purkinje fibers
      and atrium.
AB  - Neuropeptide Y exerts prejunctional effects on automaticity in cardiac pacemaker
      tissue and postjunctional effects on contractile activity of cardiomyocytes. It
      is uncertain whether neuropeptide Y has postjunctional effects on cardiac
      automaticity. This paper reports a study of the actions of exogenous neuropeptide
      Y (10(-10)-10(-6) M) on automaticity of isolated preparations of canine Purkinje
      fibers and guinea-pig right atrium. Neuropeptide Y had no effect on the rate of
      normal and abnormal (barium-induced) automaticity and did not modify the effect
      of norepinephrine on canine Purkinje fibers. Neuropeptide Y did not affect normal
      sinus rhythm in guinea-pig right atrium. The influence of neuropeptide Y (5 x 10(
      7) M) on the response to field stimulation in guinea-pig right atrium was also
      studied: neuropeptide Y reduced the vagal component of response three-fold (P <
      0.05) and insignificantly diminished the sympathetic component. Neuropeptide Y
      fragment 18-36 suppressed the vagal effect of neuropeptide Y by approximately 50%
      (P < 0.05). These results suggest that neuropeptide Y does not influence
      automaticity directly in canine Purkinje fibers and guinea-pig right atria. A
      prejunctional action to inhibit release of acetylcholine from parasympathetic
      nerve endings is implied by experiments on field-stimulated right atrium, but
      based on results with fragment 18-36, postjunctional actions may also occur here.

PMID- 8762036
TI  - Polymyxin B, a protein kinase C inhibitor, abolishes preconditioning-induced
      protection against contractile dysfunction in the isolated blood perfused rat
      heart.
AB  - The aims of this study were (1) to determine the characteristics of
      preconditioning against contractile dysfunction in a blood perfused isolated
      heart model in the presence of a physiologic combination of substrates, and (2)
      to determine if protein kinase C (PKC) is involved in preconditioning in this
      model. In order to investigate these aims, isolated isovolumic, blood perfused
      rat hearts (balloon-in-LV, n = 6/group) were perfused normoxically for 30 min and
      then divided into three groups and subjected to: (1) a further 30 min of
      perfusion (control group) (2) a further 20 min of perfusion + 5 min of ischaemia
      and 5 min of reperfusion (1 x preconditioned group) and (3) 3 x (5 min of
      ischaemia+5 min of reperfusion) (3 x preconditioned group). All hearts were then
      subjected to 30 min of ischaemia and 30 min of reperfusion. Contractile function,
      myocardial oxygen consumption (MVO2), lactate release and creatine kinase release
      were all assessed. To determine if PKC is involved in the mechanism of
      preconditioning in this model, the control and 3 x preconditioned group
      experiments were repeated in the presence of polymyxin B (50 microM), a
      relatively specific PKC inhibitor. Final recovery of LVDP was 31 +/- 12, 67 +/- 6
      and 60 +/- 5% in the control, 1 x and 3 x preconditioned groups, respectively.
      Protection of contractile function was accompanied by both a preservation of
      diastolic function and the ratio of MVO2 to contractile function (ratio of
      metabolic:mechanical efficiency). However, lactate release was decreased only in
      the 3 x preconditioned group. Polymyxin B abolished preconditioning-induced
      protection against contractile and diastolic dysfunction and the protection of
      the ratio of MVO2 to contractile function. Lactate release was still however
      reduced in the polymyxin B-preconditioned group. Thus, preconditioning-induced
      protection against contractile dysfunction appears to be accompanied by a
      preservation of both diastolic function and the metabolic: mechanical efficiency
      and is effective in the presence of a physiologic combination of substrates.
      However, limitation of glycolysis during ischaemia, as assessed by lactate
      release, appears to be an epiphenomenon of the preconditioning protocol and is
      not consistently related to protection. PKC activation appears to be pivotal to
      the mechanism of protection against contractile dysfunction, since administration
      of polymyxin B abolished any protection.

PMID- 8762037
TI  - Chemical versus isotopic equilibrium and the metabolic fate of glycolytic end
      products in the heart.
AB  - Recent studies of isotope exchange across lactate dehydrogenase (LDH) and alanine
      aminotransferase (AAT) in hearts call into question whether both reactions are in
      equilibrium. To compare the oxidative and non-oxidative fates of glycolytic end
      products, isolated rabbit hearts were perfused with 5 mM [2-13C] glucose and 2.5
      mM [3-13C] pyruvate: with (n = 6) and without (n = 7) stimulation of pyruvate
      oxidation using dichloroacetate (DCA), and during normal perfusion or hypoxia (n
      = 7/n = 6, +/- DCA). 13C NMR spectroscopy of intact hearts confirmed a steady
      state enrichment level in both alanine and lactate. 1H- and 13C-NMR spectroscopy
      of tissue extracts identified the fractions of lactate, alanine and glutamate
      pools formed from each exogenous substrate. Glycolysis from glucose accounted for
      22 +/- 7% of lactate formed and 10 +/- 2% of alanine formed in control hearts,
      and 16 +/- 2% lactate and 15 +/- 2% alanine in hypoxic hearts (mean +/- S.E.M.).
      In contrast, exogenous pyruvate formed 36 +/- 5% of the lactate pool, and 86 +/-
      3% of the alanine pool in controls and 47 +/- 3% of lactate and of 67 +/- 3%
      alanine during hypoxia. [2(-13)C] glucose did not contribute to oxidative energy
      production via the TCA cycle as determined from low 13C enrichment of glutamate
      C5 from glucose (< 2%), while [3-13C] pyruvate accounted for 84 +/- 7% of labeled
      glutamate C4. Thus, exogenous pyruvate out-competed the metabolism of glucose,
      indicating low glycolytic activity. At 40 min, 96 +/- 2% of the total alanine was
      labeled from either glucose or pyruvate, confirming equilibrium at AAT. However,
      only 55 +/- 10% of total lactate was labeled, suggesting that the LDH reaction is
      not in rapid equilibrium within the myocardium.

PMID- 8762038
TI  - Protection from myocardial reperfusion injury by acute administration of 17 beta
      estradiol.
AB  - Although several studies have demonstrated that chronic exposure to estrogen
      appears to be cardioprotective, acute circulatory effects of estrogen are largely
      unknown. Therefore, we studied the effects of acute administration of 17 beta
      estradiol in myocardial ischemia/reperfusion. Cats were subjected to 90 min of
      left anterior descending coronary artery (LAD) occlusion and 270 min of
      reperfusion (MI/R). Either the estrogenic steroid, 17 beta-estradiol or its non
      estrogenic isomer, 17 alpha-estradiol was administered (i.v.) 30 min prior to
      reperfusion at 1 microgram/kg bolus followed by a constant infusion lasting the
      remaining duration of the protocol at 1 microgram/kg/h. Control cats were
      subjected to sham MI/R. Cats treated with 17 beta-estradiol demonstrated a marked
      reduction in cardiac necrosis following MI/R compared to cats receiving 17 alpha
      estradiol or phosphate buffered saline (17 +/- 2% v 33 +/- 1% or 34 +/- 4% area
      of necrosis indexed to the area-at-risk, P < 0.01). In addition, cats receiving
      17 beta-estradiol exhibited reduced myocardial PMN infiltration in necrotic
      tissue as compared to 17 alpha-estradiol treated cats. Moreover, 17 beta
      estradiol administration attenuated neutrophil adherence to ex vivo coronary
      vascular endothelium compared to the two controls (44 +/- 8 PMNs/mm2 v 79 +/- 7
      PMNs/mm2 or 86 +/- 7 PMNs/mm2 P < 0.01). These data indicate that 17 beta
      estradiol protects against myocardial ischemia/reperfusion, in part, by
      attenuating PMN infiltration and subsequent injury due to PMN mediator release.

PMID- 8762039
TI  - G protein expression in human fetoplacental vascularization. Functional evidence
      for Gs alpha and Gi alpha subunits.
AB  - GTP-binding proteins are key elements in coupling receptors to various effector
      systems. Using ADP-ribosylation by cholera (CTX) and pertussis (PTX) toxins and
      an immunodetection technique, we investigated the G protein expression profile in
      smooth muscle of stem villi vessels obtained from human term placentae. In
      placental vascular smooth muscle, we report the presence of two CTX-protein
      substrates of 42 and 45 kDa recognized by Gs alpha antibodies, and three Gi alpha
      isoforms, substrates of PTX, identified as Gi1 alpha, Gi3 alpha (two proteins of
      41 kDa) and Gi2 alpha (a 40-kDa protein). We also characterized another target of
      PTX, a 40-kDa Go alpha-immunoreactive protein and detected the PTX-insensitive Gq
      Gi1 alpha proteins. To assess the functional significance of the G alpha proteins
      identified in this tissue, we measured the adenylyl cyclase activity in the
      presence of guanyl nucleotides alone or with increasing concentrations of
      vasoactive intestinal peptide (VIP), and examined whether VIP-bound sites, in the
      presence of GTP gamma S, promote the release of G alpha proteins from the
      membranes of vascular smooth muscle. At low concentrations (0.1 nM to 0.01
      microM), guanyl nucleotides stimulated adenylyl cyclase activity in a dose
      dependent manner, while at higher concentrations (10 microM to 1 mM) the
      stimulation rate of cAMP production by guanyl nucleotides decreased. In a dose
      dependent manner, VIP in the presence of GTP gamma S increased adenylyl cyclase
      activity and specifically promoted the release of both Gs alpha isoforms. In
      contrast, the release of Gi1 and Gi2 alpha isoforms was not significantly
      increased in the presence of VIP, while GTP gamma S alone stimulated their
      release. Our data show physical evidence of the activation of Gs proteins by VIP
      bound membrane receptors, resulting in dissociation and release of Gs alpha
      subunits in the soluble fraction. They assess the specific coupling of the two Gi
      alpha isoforms to VIP receptors in smooth muscle wall of placental stem villi
      vessels. It would be of interest to investigate whether changes in Gs alpha
      expression and/or function are associated with the placental angiogenesis process
      during pregnancy.

PMID- 8762040
TI  - Dose-dependent increase in sensitivity to calcium-induced mitochondrial
      dysfunction and cardiomyocyte cell injury by doxorubicin.
AB  - We previously reported the induction of calcium-dependent calcium release and
      depolarization of membrane potential of cardiac mitochondria from rats treated
      chronically (13 weeks) with doxorubicin. The fact that this was inhibited by
      cyclosporine A and ruthenium red suggests induction of the mitochondrial
      permeability transition and calcium cycling. The objective of this investigation
      was to characterize the cumulative dose-dependent interference with mitochondrial
      calcium transport by doxorubicin and to assess whether alteration of
      mitochondrial calcium regulation is manifested as an increased sensitivity to
      calcium-induced injury to cardiomyocytes isolated from rats exposed in vivo.
      Mitochondria or cardiomyocytes were isolated from rats treated with 2 mg/kg/week
      doxorubicin s.c. for 1-9 weeks. Mitochondria isolated from hearts of doxorubicin
      treated rats exhibited a dose-dependent increase in sensitivity to calcium
      induced calcium release and membrane depolarization, both of which were inhibited
      by cyclosporine A. Cardiomyocytes isolated from rats treated for 6 weeks with
      doxorubicin expressed an increased sensitivity to calcium-induced cell killing.
      The calcium intolerance was prevented by adding either cyclosporine A or
      ruthenium red to block mitochondrial calcium cycling. These data demonstrate that
      doxorubicin treatment in vivo causes: (1) a dose-dependent interference with
      mitochondrial calcium transport and calcium-dependent regulation of membrane
      potential indicative of induction of the mitochondrial permeability transition,
      and (2) an increased sensitivity to calcium-induced loss of cell viability. The
      fact that blocking mitochondrial calcium cycling protected cardiomyocytes from
      the calcium intolerance suggests that altered regulation of mitochondrial calcium
      transport may be a critical event in doxorubicin-induced cardiomyopathy.

PMID- 8762041
TI  - Cardiac alpha-adrenergic receptor expression is regulated by thyroid hormone
      during a critical developmental period.
AB  - Although thyroid hormone is obligatory for the development of cardiac beta
      adrenergic receptors, it is difficult to assign a specific role for the hormone
      in receptor ontogeny because beta-receptor expression is affected similarly in
      the adult. We have determined whether thyroid hormone plays a role in receptor
      development by evaluating alpha 1-adrenergic receptors, which in the adult are
      downregulated by thyroid hormone. Propylthiouracil given from gestational day 17
      through postnatal day 5 caused significant deficits in the number of alpha 1
      receptors and values resolved to normal in parallel with hormone level recovery.
      When propylthiouracil was administered later (postnatal days 11 through 15) only
      a transient deficit in alpha 1-receptor binding was seen; hyperthyroidism
      (triiodothyronine) could still evoke stimulation of receptor expression at this
      stage. The effects on receptor expression were distinguished from general effects
      on cell differentiation by examining alpha 2-receptors, which disappear over the
      first three postnatal weeks; delayed differentiation caused by propylthiouracil
      would slow the decline in alpha 2-receptors, whereas accelerated differentiation
      caused by triiodothyronine would hasten the decline. Instead, the effects were
      similar to those on alpha 1-receptors: perinatal propylthiouracil administration
      reduced, and neonatal triiodothyronine administration enhanced, alpha 2-receptor
      binding sites. Thus, thyroid hormone plays a role in the control of cardiac
      adrenergic receptor expression during a critical development period, with
      conjoint regulation of the multiple receptor subtypes present within the tissue.
      As adrenergic stimulation is important in maintaining cardiac function in the
      perinatal period, alterations of thyroid status during this period can be
      expected to result in abnormal reactivity and increased perinatal risk.

PMID- 8762042
TI  - Paradoxical effect of ischemic preconditioning on ischemic contracture? NMR
      studies of energy metabolism and intracellular pH in the rat heart.
AB  - Using the blood-perfused rat heart, we have previously shown that although
      ischemic preconditioning (PC) and cardioplegia (CP) afforded similar protection
      against post-ischemic contractile dysfunction this effect was not additive even
      though PC accelerated whereas CP delayed ischemic contracture. Using NMR we
      examined the effects of these interventions on pHi and ATP metabolism during
      global ischemia. Isolated rat hearts (n = 6/group) with an intraventricular
      balloon were aerobically perfused with buffer, subjected to zero flow ischemia
      (37 degrees C) for 35 min and reperfused for 40 min. The groups were: (1)
      controls without protection, (2) PC (2 cycles), and (3) St Thomas' cardioplegia,
      prior to test ischemia. PC accelerated whereas CP delayed ischemic contracture (P
      < 0.05 v controls). Yet, after 40 min reperfusion, both interventions produced
      substantial improvements in the recovery of LVDP (P < 0.05 v controls). During 35
      min ischemia, the decline of ATP was delayed by CP but accelerated by PC (P <
      0.05 v controls). The pHi fell steeply in controls to a plateau of 5.9 after 14
      min ischemia. PC had no effect on the rate of fall of pHi but reduced its extent
      (P < 0.05). CP delayed the onset of the decline in pHi (P < 0.05) but, once
      initiated, there was no effect on the rate of decline to a plateau. Thus, despite
      protecting post-ischemic contractile function, PC accelerated ischemic
      contracture and the depletion of ATP, but substantially reduced intracellular
      acidosis. In contrast, CP slowed ischemic contracture and the depletion of ATP;
      it also delayed the onset of acidosis.

PMID- 8762043
TI  - Importance of calcium for the vulnerability to ventricular fibrillation detected
      by premature ventricular stimulation: single pulse versus sequential pulse
      methods.
AB  - Vulnerability to ventricular fibrillation (VF) is frequently evaluated by VF
      threshold, a variable which may not be free of confounding factors and which may
      not be sensitive to all factors contributing to vulnerability. Therefore, we
      tested whether VF threshold determination affects intracellular free Ca2+
      ([Ca2+]i) and whether VF thresholds are sensitive to changes in [Ca2+]i. For this
      purpose, we analysed [Ca2+]i by surface fluorometry and indo-1 in intact perfused
      rat hearts undergoing VF threshold determination by a single pulse method and
      tested whether such thresholds are lowered by increased [Ca2+]i. Additionally, we
      sought to determine the importance of Ca2+ for the vulnerability to VF under
      nonischemic conditions. For this purpose, we measured VF thresholds by a new
      pulse number method which scanned the vulnerable period by an increasing number
      of sequential pulses at increasing prematurity but constant intensity. We found
      that VF threshold determination by a single pulse method led to a rise in
      systolic [Ca2+]i. However, this rise does not perturb VF threshold interpretation
      because such thresholds were insensitive to changes in [Ca2+]i. Nevertheless,
      [Ca2+]i is of importance for the vulnerability to VF under nonischemic conditions
      because the number of VF-free tolerated premature pulses was dependent on
      [Ca2+]i. This relationship may only be detectable if evaluated by sequential
      pulse methods. These findings suggest that the method of VF threshold
      determination may be crucial for the result of studies testing Ca2+ antagonists
      or situations of altered [Ca2+]i and could explain controversial results of VF
      threshold studies testing Ca2+ antagonists by varying methods.

PMID- 8762044
TI  - Cyclic AMP-dependent protein kinase and mechanical heart function in ventricular
      hypertrophy induced by pressure overload or secondary to myocardial infarction.
AB  - The role of cyclic AMP-dependent protein kinase (PKA) and systolic function
      during the development of left ventricular hypertrophy (LVH) still remain
      uncertain. The aim of this work is to study PkA activity and mechanical heart
      function in two experimental heart hypertrophy models: specifically, one induced
      by pressure overload (Goldblatt model: two kidneys, one clamped, Gb); and another
      secondary to myocardial infarction (MI) generated by ligation of the left
      coronary artery. Hypertension in the Gb group becomes evident by the third and
      fourth week after surgery without any significant change in the corresponding
      sham group. The myocardial infarction group did not show any change in systolic
      pressure. Different degrees of LVH for the two experimental models were observed.
      Relative cardiac mass (RCM) and relative ventricular mass (RVM) increased 23 and
      16%, respectively, above the sham-operated rats in MI group (P < 0.05). For the
      pressure overload model, the increase values were 42 and 44%, respectively (P <
      0.05). Left ventricular hypertrophy was also evaluated through quantitative
      changes in cardiac beta-myosin heavy chain which agreed with morphometric studies
      in Goldblatt rats. Ventricular PKA activity did not show any significant
      difference with respect to the sham-operated group after induction of pressure
      overload. For the MI model, ventricular PKA activity changed only at day 7 post
      infarction with a 289% increase above the sham-operated group (P < 0.05). The
      absence of activation of ventricular PKA after constriction of renal artery or
      myocardial infarction was also corroborated by the patterns of PKA-dependent
      phosphorylated proteins. While force-generating capacity was increased, there was
      no change in ventricular PKA activity, indicating that there is no relation
      between this enzyme and systolic stress-strain regression lines in either
      pressure overload or myocardial infarction conditions. Cyclic AMP-dependent
      protein kinase activity had no relation with development of cardiac hypertrophy
      in the two experimental models of LVH. These findings contribute to the
      hypothesis for a multifactorial interaction of different intracellular
      biochemical and molecular mechanisms in the genesis of cardiac hypertrophy.

PMID- 8762045
TI  - [3H]dofetilide binding: biological models that manifest solely the high or the
      low affinity binding site.
AB  - Dofetilide is a Class III antiarrhythmic agent known to selectively block the
      rapid component of the delayed rectifier K+ current (IKr). [3H]Dofetilide binds
      to a low and a high affinity sites on guinea-pig myocytes. The purposes of this
      study were: (1) to find biological models which express solely the high or the
      low [3H]dofetilide binding sites; (2) to characterize the single binding site
      models; and (3) to establish which of the high or the low affinity binding sites
      is associated with IKr. We compared and characterized the [3H]dofetilide binding
      on guinea-pig myocytes, neonatal mouse ventricular homogenate and untransfected
      CHO cells. These tissue preparations were selected since the neonatal mouse
      tissue expresses IKr while this current is absent from CHO cells. We compared the
      IC50 concentrations of dofetilide and two other known IKr blockers E-4031 and
      sotalol, on [3H]dofetilide binding to these three preparations. Using steady
      state and kinetic binding techniques, we characterized the interaction of E-4031
      and sotalol with the high and the low [3H]dofetilide binding sites. We found that
      neonatal mouse ventricle manifest solely the high affinity site (Kd 20 +/- 4
      nmol/l, Bmax 18 +/- 4 fmol/mg) while CHO cells manifest solely the low affinity
      binding site (Kd 1.6 +/- 0.1 mumol/l, Bmax 5.8 +/- 0.8 pmol/mg). We demonstrated
      that the high and low affinity binding sites present on guinea-pig myocytes show
      characteristics similar to the single high affinity site expressed on neonatal
      mouse homogenate and to the single low affinity site expressed on CHO cells,
      respectively. Class III antiarrhythmic drugs inhibited binding to the high
      affinity site at concentrations similar to those required to inhibit 50% of IKr
      current in electrophysiologic studies. In contrast, dofetilide and E-4031
      inhibited [3H]dofetilide binding to the low affinity site only at supra
      pharmacologic concentrations. We next demonstrated that Class III drugs interact
      in a competitive manner with the high affinity site on neonatal mouse tissue
      while they interact with a site allosterically coupled to the low binding site on
      CHO cells. These data suggest that dofetilide interacts with the high and low
      affinity sites in a fundamentally different manner. We defined biological models
      which express solely the high or low [3H]dofetilide binding sites. Only the high
      affinity site is related to IKr.

PMID- 8762046
TI  - Eicosapentaenoic acid incorporation in membrane phospholipids modulates receptor
      mediated phospholipase C and membrane fluidity in rat ventricular myocytes in
      culture.
AB  - The influence of increased incorporation of linoleic acid (18:2n-6) and
      eicosapentaenoic acid (20:5n-3) in membrane phospholipids on receptor-mediated
      phospholipase C beta (PLC-beta) activity in cultured rat ventricular myocytes was
      investigated. For this purpose, cells were grown for 4 days in control, stearic
      acid (18:0)/oleic acid (18:1n-9), 18:2n-6 and 20:5n-3 enriched media, and
      subsequently assayed for the basal- and phenylephrine- or endothelin-1-induced
      total inositol phosphate formation. The various fatty acid treatments resulted in
      the expected alterations of fatty acid composition of membrane phospholipids. In
      18:2n-6-treated cells, the incorporation of this 18:2n-6 in the phospholipids
      increased from 17.1 mol % in control cells to 38.9 mol %. In 20:5n-3-treated
      cells, incorporation of 20:5n-3 and docosapentaenoic acid (22:5n-3) in the
      phospholipids increased from 0.5 and 2.7 mol % in control cells to 23.2 and 9.7
      mol %, respectively. When 20:5n-3-treated cells were stimulated with
      phenylephrine or endothelin-1, the inositolphosphate production decreased by
      33.2% and increased by 43.4%, respectively, as compared to cells grown in control
      medium. No effects were seen in 18:2n-6-treated cells. When 18:0/18:1n-9-treated
      cells were stimulated with endothelin-1, inositolphosphate formation increased by
      26.4%, whereas phenylephrine-stimulated inositolphosphate formation was not
      affected. In saponin-permeabilized cells, that were pre-treated with 20:5n-3, the
      formation of total inositolphosphates after stimulation with GTP gamma S, in the
      presence of Ca2+, was inhibited 19.3%. This suggests that the 20:5n-3 effect on
      intact cardiomyocytes could be exerted either on the level of agonist-receptor,
      receptor-GTP-binding-protein coupling or GTP-binding-protein-PLC-beta
      interaction. Investigation of the time course of saponin-induced permeabilization
      of the cardiomyocytes, measured by the release of lactate dehydrogenase, unmasked
      a slight decrease in the rate of permeabilization by 20:5n-3 pretreatment,
      indicating a protective effect. This led the authors to measure the
      cholesterol/phospholipid molar ratio, the double bond index of membrane
      phospholipids, and the membrane fluidity; the latter by using a
      diphenylhexatriene probe. In 20:5n-3-pretreated cells, a strong increase in the
      cholesterol/phospholipid molar ratio (from 0.23 to 0.39), a marked increase in
      the double bond index (from 1.76 to 2.33), and a slight decrease in fluidity
      (steady-state anisotropy rss of the diphenylhexatriene probe increased from 0.196
      to 0.217) were observed. Thus, treatment of cardiomyocytes for 4 days with 20:5n
      3, but not with 18:2n-6, causes alterations of receptor-mediated phospholipase C
      beta activity. A causal relationship may exist between the 20:5n-3 causes
      alterations of the physicochemical properties in the bilayer and of the agonist
      stimulated phosphatidylinositol cycle activity.

PMID- 8762049
TI  - Modulation of the electrophysiological effects of ischemia reperfusion by
      methylisobutyl amiloride.
AB  - We studied the effect of the Na+/H+ exchanger inhibitor methylisobutyl amiloride
      (MIA, 1 microM) on action potential characteristics and arrhythmias induced by:
      (a) reperfusion following regional ischemia in rat hearts and (b) realkalization
      after lactate acidosis in rabbit hearts. We also determined the effect of MIA on
      the incidence of transient inward currents (ITIs) induced by acidosis
      realkalization in rabbit cardiocytes. Ligation of the LAD coronary artery for 10
      min depolarized the resting potential from -78 +/- 1.9 mV to -66.9 +/- 1.0 mV and
      depressed the action potential but did not induce overt arrhythmias. Delayed
      afterdepolarizations were observed during ischemia in 50% of untreated hearts
      whereas reperfusion produced severe ventricular tachyarrhythmias in all of them.
      MIA reduced the incidence of arrhythmias to 27% and their duration to less than 1
      min. MIA increased action potential duration by 38 +/- 4.1%. BaCl2 produced a
      similar APD lengthening and had an antifibrillatory effect. Acidic reperfusion
      induced bradycardia and reduced severity of arrhythmias. In rabbit hearts, MIA
      increased the action potential duration by 61 +/- 4.3% and abolished arrhythmias
      on realkalization. Eleven out of 18 cells developed transient inward currents
      during acidosis-realkalization and seven of them underwent irreversible injury.
      MIA prevented the appearance of ITIs, had no effect on ICa,L but decreased the
      outward component of IK1 by 50%. Our results suggest that the protective effect
      of MIA is in part due to changes in cellular electrical activity that modulate
      Na+ and Ca2+ entry via different pathways.

PMID- 8762047
TI  - Betaine generation in cardiac myocytes after adrenergic activation of
      phosphatidylcholine hydrolysis.
AB  - In this report, effects of alpha 1-adrenergic stimulation on phosphatidylcholine
      (PC) hydrolysis and the subsequent generation of water-soluble choline
      metabolites were investigated after preincubation of isolated cardiac myocytes of
      adult rats with [methyl-3H]choline. Choline uptake into cardiac myocytes was
      apparently mediated by a choline carrier which could be inhibited by
      hemicholinium-3. Analysis of the intracellular choline metabolites was performed
      by HPLC. Adrenergic stimulation of cardiac myocytes by (-)-phenylephrine, which
      is also known to activate the phosphoinositide signaling system, induced the
      generation of betaine as a selective signal transduction response. Agonist
      induced generation of betaine in cardiac myocytes was maximal at 10 min after
      stimulation, and was optimal at physiologically relevant (-)-phenylephrine
      concentrations (1-10 microM). Betaine accumulation was transient, and no betaine
      remained detectable after 15 min. CDP-choline, however, was still elevated after
      15 min which is indicative of continued PC resynthesis after adrenergic
      stimulation. The source of betaine in cellular signalling appeared to be
      hydrolysis of membrane PC to phosphatidic acid and choline by phospholipase D
      with subsequent oxidation of choline to betaine. This is based on the observation
      that radioactivity in unstimulated cells is present only in the lipid phase
      (presumably as PC) or as phosphocholine in the aqueous phase of the cells. The
      latter finding suggests that choline is rapidly phosphorylated after uptake into
      cardiac myocytes. Collectively, these results suggest a hypothetical role of
      betaine in the cellular signal transduction response to alpha 1-adrenergic
      stimulation in cardiac myocytes.

PMID- 8762048
TI  - Altered mRNA abundance of calcium transport genes in cardiac myocytes induced by
      angiotensin II.
AB  - Recent studies have implicated angiotensin II (angiotensin) in the pathogenesis
      of cardiac hypertrophy and heart failure. Heart failure is associated with
      alterations in intracellular Ca2+ movements mediated by sarcolemmal (SL) and
      sarcoplasmic reticular (SR) membranes in cardiac myocytes. As it was suspected
      that alteration gene expression of proteins responsible for controlling
      transmembrane Ca2+ fluxes may contribute to loss of Ca2+ homeostasis in failing
      hearts, we undertook a study of the effect of angiotensin on the expression of
      some target genes in the myocardium. Specifically, we tested the effect of
      angiotensin on mRNA abundance of cardiac Ca(2+)-transport genes including SL
      Na+/Ca2+ exchange (EX), SR ryanodine receptor (RYR), and sarco(endo)plasmic
      reticulum Ca(2+)-ATPase (SERCA). The mRNA abundance of target gene was assessed
      by Northern blot assay in (i) direct hormonal stimulation of cultured isolated
      neonatal and adult rat myocytes and (ii) adult rat hearts after implantation of
      osmotic mini-pumps for delivery of hormone. In all experiments, Northern blot
      data were normalized using cDNA (Glyceraldehyde 3-phosphate dehydrogenase signal,
      GAPDH) hybridization to RNA samples. The results indicate that the ratios of
      EX/GAPDH, RYR/GAPDH, and SERCA2/GAPDH signals were decreased by 51.6%, 55.0%, and
      49.4% respectively after neonatal cardiac myocytes were treated (24 h) with 10(
      7) M angiotensin. These decreases were blocked completely by treatment with
      angiotensin subtype 1 (AT1) receptor antagonist (losartan), whereas angiotensin
      subtype 2 (AT2) receptor antagonist (PD123319) treatment had no effect on the
      angiotensin-mediated decrease in target gene mRNA abundance. In contrast,
      angiotensin had no effect on EX, RYR nor SERCA2 gene mRNA abundance in cultured
      adult myocytes. In a separate series of experiments wherein adult male Sprague
      Dawley rats were infused with different dose of angiotensin for 3 days via
      osmotic mini-pump, we did not detect any alterations in mRNA abundance of cardiac
      EX/GAPDH, RYR/GAPDH or SERCA/GAPDH genes in either left or right ventricular
      samples. Thus our results indicate that, in neonatal rat myocytes, angiotensin
      affects SL and SR calcium transport gene expression by direct agonism of AT1
      receptors. As the infusion of low and high dose angiotensin did not affect the
      expression of target genes in adult hearts, we suggest that the mechanisms for
      transduction of the angiotensin signaling in neonatal and adult myocytes may be
      different and may depend on the stage of development. We conclude that regulation
      of myocardial Ca(2+)-transport gene mRNA abundance by angiotensin may differ
      among neonatal and adult animals. Nonetheless, our finding with respect to
      neonatal preparation led us to believe that in neonatal myocytes, the mRNA
      abundance of SL Na+/Ca2+ exchange, SR ryanodine receptor, and SR Ca(2+)-ATPase
      are all decreased in response to stimulation by angiotensin.

PMID- 8762050
TI  - Maturational differences in bioenergetic state and purine formation during
      "supply" and "demand" ischemia.
AB  - We examined metabolic effects of "supply" and "demand" ischemia in immature and
      mature rabbit hearts. Moderate supply ischemia was produced by a 50% reduction in
      coronary flow (to approximately 5.0 ml min-1 g-1 giving a 50-55% rise in O2
      extraction and a 35% drop in O2 supply/demand). Demand ischemia was produced by
      stimulation of workload and O2 demand with 30 microM norepinephrine at constant
      coronary flow (55-60% rise in O2 extraction, 35-40% fall in O2 supply/demand).
      Basal energy state ([ATP]/[ADP].[Pi]) was lower in immature compared to mature
      hearts, primarily due to reduced [PCr]. Despite a lower energy state, basal
      purine efflux was lowest in immature hearts. During supply ischemia reductions in
      [ATP]/[ADP]. [Pi] and elevations in [H+] were greatest in mature compared to
      immature hearts (P < 0.05). Despite this depressed energy state purine efflux did
      not increase significantly during supply ischemia. In contrast, during demand
      ischemia reductions in energy state were greatest in immature compared to mature
      hearts. Moreover, purine efflux increased more than 30-fold in immature and only
      four-fold in mature hearts, resulting in two-fold greater purine washout in
      immature hearts. The data indicate that: (i) maturation increases basal energy
      state and, paradoxically, purine efflux, (ii) in immature hearts demand ischemia
      has a greater impact on energy state than supply ischemia, whereas there are
      minimal differences in the metabolic effects of supply and demand ischemia in
      mature hearts, (iii) consequently while maturation is associated with a reduction
      in metabolic/bioenergetic resistance to supply ischemia it is associated with
      increased resistance to demand ischemia, (iv) markedly reduced purine wash-out
      from mature myocardium may contribute to this increased resistance during demand
      ischemia, and (v) control of adenosine formation and purine efflux changes with
      maturation, and appears to involve mechanisms unrelated to cytosolic energy
      metabolism.

PMID- 8762051
TI  - Chronic exposure of neonatal cardiac myocytes to hydrogen peroxide enhances the
      expression of catalase.
AB  - The adaptive response of antioxidant enzymes to oxidative stress in the heart has
      not been investigated. Because H2O2 is considered to play a major role in
      reperfusion injury to the heart, this study was undertaken to examine if H2O2
      alters the expression of these enzymes in the rat neonatal myocytes. H2O2 was
      continuously generated by the addition of glucose oxidase to the culture medium.
      Both the activity and the mRNA for catalase were increased following incubation
      of neonatal myocytes with non-toxic concentrations of glucose oxidase. The
      induction of mRNA preceded the enhancement of activity, and both remained
      elevated after 24 h incubation. Nuclear run-on assay indicated that the
      transcriptional rate for catalase mRNA was increased. The same treatment did not
      alter the activities for total superoxide dismutase and Se-glutathione
      peroxidase. The results suggest that H2O2-induced expression of catalase was in
      part due to transcriptional activation. It further implies that the induction of
      catalase may play an important role in protecting hearts from
      ischemic/reperfusion injury.

PMID- 8762052
TI  - Transient ischemia in the presence of an adenosine deaminase plus a nucleoside
      transport inhibitor confers protection against contractile depression produced by
      hydrogen peroxide. Possible role of glycogen.
AB  - We previously reported that adenosine A1 receptor activation protects against the
      cardiodepressant effects of hydrogen peroxide in isolated rat hearts. The present
      study examined whether a transient ischemic period of 5 min duration, which
      preconditions the heart against ischemic and reperfusion-induced dysfunction, can
      bestow protection against 30-min exposure to hydrogen peroxide in isolated rat
      hearts. Transient ischemia on its own failed to alter the cardiac response to
      hydrogen peroxide. However, when transient ischemia was carried out in the
      presence of the nucleoside transport inhibitor S-(4-Nitrobenzyl)-6-thioguanosine
      and the adenosine deaminase inhibitor erythro-9-(2-Hydroxy-3-nonyl)adenine, a
      significant attenuation of the hydrogen peroxide-induced loss in contractility
      was evident and this was associated with significant preservation of tissue
      glycogen content. The protective effect of the transient ischemia/drug
      combination on both functional changes and glycogen levels was abolished by the
      adenosine A1 receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine as well as
      by glibenclamide, a blocker of the ATP-sensitive potassium channel (KATP). To
      further assess the role of glycogen in the protection against hydrogen peroxide,
      we compared the effects of the adenosine A1 agonist N6-cyclopentyl adenosine
      (CPA) and insulin. While both treatments protected against hydrogen peroxide the
      effect of insulin was superior to any other treatment. Moreover, while all
      protective modalities preserved glycogen stores after hydrogen peroxide
      treatment, the protection afforded by insulin was also associated with
      significantly elevated glycogen levels prior to hydrogen peroxide administration.
      No protection by either CPA or insulin was evident in the absence of exogenous
      glucose. Taken together, our results demonstrate that a brief period of ischemia
      with concomitant administration of agents which increase interstitial adenosine
      levels protects against hydrogen peroxide toxicity. The effect is mediated by
      activation of adenosine A1 receptors and is linked to KATP stimulation. Moreover,
      our results are strongly suggestive of an important role of glycogen preservation
      in bestowing protective effects against hydrogen peroxide cardiotoxicity.

PMID- 8762053
TI  - Suspension culture of differentiated rat heart myocytes on non-adhesive surfaces.
AB  - Cardiac myocytes isolated from adult rat ventricles have been maintained in a
      stable, differentiated state for prolonged periods by the use of suspension
      culture on hydrophobic tissue culture inserts or agarose-coated plates. The
      success of this procedure depends on the use of low-serum media to prevent
      myocyte-myocyte interaction and proliferation of any residual endothelial cells.
      Myocytes cultured in this manner retain many of their structural characteristics,
      suggesting that maintenance of their elongated irregular shape is not dependent
      on interaction with extracellular matrix. They also exclude trypan blue, can be
      vitally stained by the uptake and reduction of the tetrazolium dye MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide], synthesize myosin and
      when returned to adhesive surfaces are capable of attachment and attendant
      dedifferentiation. Stability of the myocytes in suspension permits their use in
      co-culture experiments; specifically, myocytes separated from endothelial cells
      by the hydrophobic membrane of the tissue culture insert stimulated proliferation
      of the latter cells, suggesting this to be a useful system for studying myocyte
      endothelial cell interaction.

PMID- 8762054
TI  - Increased expression of a homologue of drosophila tissue polarity gene "frizzled"
      in left ventricular hypertrophy in the rat, as identified by subtractive
      hybridization.
AB  - The molecular mechanisms that govern the development of left ventricular
      hypertrophy are not fully elucidated. We performed a subtractive hybridization
      procedure to identify genes controlling this adaptive process. Using this
      approach, we isolated a rat homologue of Drosophila tissue polarity gene
      "frizzled" 2 (fz-2). The expression of this gene was quantified by competitive
      reverse transcriptase polymerase chain reactions. The expression was higher in
      hypertrophic left ventricles at all time points tested, reaching statistical
      significance at days 1 and 10. We conclude that the fz-2 gene, a highly conserved
      gene for which a role in intra- and intercellular communication has been
      described, may be involved in the spatial control of ventricular remodeling.

PMID- 8762056
TI  - Immunocytochemical electron microscopic study and western blot analysis of
      paramyosin in different invertebrate muscle cell types of the fruit fly
      Drosophila melanogaster, the earthworm Eisenia foetida, and the snail Helix
      aspersa.
AB  - The presence and distribution pattern of paramyosin have been examined in
      different invertebrate muscle cell types by means of Western blot analysis and
      electron microscopy immunogold labelling. The muscles studied were: transversely
      striated muscle with continuous Z lines (flight muscle from Drosophila
      melanogaster), transversely striated muscle with discontinuous Z lines (heart
      muscle from the snail Helix aspersa), obliquely striated body wall muscle from
      the earthworm Eisenia foetida, and smooth muscles (retractor muscle from the
      snail and pseudoheart outer muscular layer from the earthworm). Paramyosin-like
      immunoreactivity was localized in thick filaments of all muscles studied.
      Immunogold particle density was similar along the whole thick filament length in
      insect flight muscle but it predominated in filament tips of fusiform thick
      filaments in both snail heart and earthworm body wall musculature when these
      filaments were observed in longitudinal sections. In obliquely sectioned thick
      filaments, immunolabelling was more abundant at the sites where filaments
      disappeared from the section. These results agree with the notion that paramyosin
      extended along the whole filament length, but that it can only be immunolabelled
      when it is not covered by myosin. In all muscles examined, immunolabelling
      density was lower in cross-sectioned myofilaments than in longitudinally
      sectioned myofilaments. This suggests that paramyosin does not form a continuous
      filament. The results of a semiquantitative analysis of paramyosin-like
      immunoreactivity indicated that it was more abundant in striated than in smooth
      muscles, and that, within striated muscles, transversely striated muscles contain
      more paramyosin than obliquely striated muscles.

PMID- 8762057
TI  - Microfluorometric kinetic analysis of cathepsin B activity in single human
      thyroid follicular epithelial cells using image analysis and continuous
      monitoring.
AB  - The activity of a cysteine proteinase, cathepsin B (EC 3.4.22.1), was determined
      in unfixed single human thyroid follicular epithelial cells at room temperature
      using an image analysis system. The formation of the reaction product was
      monitored every minute by measuring the increasing fluorescence intensity of
      emitted light from a Schiff-base product formed by the substrate N-CBZ-ala-arg
      arg-4-methoxy-2-naphthylamide and the coupling agent 5-nitrosalicylaldehyde. Non
      specific fluorescent signals were eliminated by adjusting the video signal to
      zero using leupeptin, a specific inhibitor of cathepsins B, H and L. The enzyme
      activity was expressed as fluorescence intensity versus time. After a mean lag
      period of 5 min (range 4-8 min, n = 4), the enzyme activity increased linearly
      lasting on average 5 min (range 3-8 min), followed by a marked decrease in
      reaction rate for 3 min (range 1-4 min), and another linear increase for 11 min
      (range 8-14 min). The second linear part of the curve was not as steep as the
      first one. The reaction velocity recorded in individual granules resulted either
      in a biphasic curve or straight line, suggesting the presence of two distinct
      organelle compartments with differences in membrane permeability. It is concluded
      that human thyroid follicular epithelial cells in culture exhibit cathepsin B
      activity which can be monitored continuously by videomicrofluorometry without
      interference from non-specific fluorescence.

PMID- 8762058
TI  - Changes in the content of the fibrillar collagens and the expression of their
      mRNAs in the menisci of the rabbit knee joint during development and ageing.
AB  - The menisci are first seen as triangular aggregations of cells in the 20-day
      rabbit fetus. At 25-days, a matrix that contains types I, III and V collagens has
      formed. These collagens are also found in the 1-week neonatal meniscus, but by 3
      weeks, type II collagen is present in some regions. By 12 to 14 weeks, typically
      cartilaginous areas with large cells in lacunae are found and by 2 years, these
      occupy the central regions of the inner two-thirds of the meniscus. The surface
      layers of the meniscus contain predominantly type I collagen. From 12 to 14 weeks
      onwards, there is little overlap between the regions with types I or II
      collagens, that is, these are discrete regions of type I-containing
      fibrocartilage and type II-containing cartilage. Types III and V collagens are
      found throughout the menisci, particularly in the pericellular regions. All the
      cells in the fetal and early neonatal menisci express the mRNA for type I
      collagen. At 3 weeks postnatal, cells that express type I collagen mRNA are found
      throughout the meniscus, but type II collagen mRNA is expressed only in the
      regions of developing cartilage. At 12- to 14-weeks, only type II collagen mRNA
      is expressed, except at the periphery next to the ligament where a few cells
      still express type I collagen mRNA. Rabbit menisci, therefore, undergo profound
      changes in their content and arrangement of collagens during postnatal
      development.

PMID- 8762055
TI  - Phagocytosis and intracellular digestion of collagen, its role in turnover and
      remodelling.
AB  - Collagens of most connective tissues are subject to continuous remodelling and
      turnover, a phenomenon which occurs under both physiological and pathological
      conditions. Degradation of these proteins involves participation of a variety of
      proteolytic enzymes including members of the following proteinase classes: matrix
      metalloproteinases (e.g. collagenase, gelatinase and stromelysin), cysteine
      proteinases (e.g. cathepsin B and L) and serine proteinases (e.g. plasmin and
      plasminogen activator). Convincing evidence is available indicating a pivotal
      role for matrix metalloproteinases, in particular collagenase, in the degradation
      of collagen under conditions of rapid remodelling, e.g. inflammation and
      involution of the uterus. Under steady state conditions, such as during turnover
      of soft connective tissues, involvement of collagenase has yet to be
      demonstrated. Under these circumstances collagen degradation is likely to take
      place particularly within the lysosomal apparatus after phagocytosis of the
      fibrils. We propose that this process involves the following steps: (i)
      recognition of the fibril by membrane-bound receptors (integrins?), (ii)
      segregation of the fibril, (iii) partial digestion of the fibril and/or its
      surrounding non-collagenous proteins by matrix metalloproteinases (possibly
      gelatinase), and finally (iv) lysosomal digestion by cysteine proteinases, such
      as cathepsin B and/or L. Modulation of this pathway is carried out under the
      influence of growth factors and cytokines, including transforming growth factor
      beta and interleukin 1 alpha.

PMID- 8762059
TI  - Ultrastructural identification of apoptotic nuclei using the TUNEL technique.
AB  - We describe an ultrastructural adaptation of the method of terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) for
      the identification of DNA fragmentation. Thin sections of tissue embedded in
      hydrophilic resin were nick end labelled with biotinylated dUTP which was
      subsequently labelled with avidin conjugated to gold particles. The technique was
      validated by labelling the nuclei of L929-8 cells treated with tumour necrosis
      factor alpha. These cells are known to respond to treatment with the factor by
      undergoing apoptosis. The method was then used on tissue from the chick embryo
      which is known to be undergoing programmed cell death. This tissue was from the
      neural tube and the posterior necrotic zone of the limb bud, where cells can be
      identified as undergoing apoptosis based on the morphology of their nuclei. The
      method specifically labelled heterochromatin adjacent to the nuclear envelope as
      well as that associated with the nucleolus of cells from regions of the embryo
      where programmed cell death was expected. In addition to labelling the nuclei of
      cells that were clearly undergoing apoptosis, the method also identified nuclei
      of apparently normal cells. This method, used in conjunction with corroborating
      techniques, provides a means for the early detection of cells undergoing DNA
      fragmentation, before the onset of gross apoptotic morphology, and in cells that
      do not show classical apoptotic characteristics.

PMID- 8762060
TI  - Detection of alpha 1-adrenoceptor subtypes in human hypertrophied prostate by in
      situ hybridization.
AB  - Adrenergic stimulation induces contraction of hypertrophied prostatic tissue via
      the alpha 1 adrenoceptor, and the results of pharmacological studies suggested
      the existence of adrenoceptor subtypes. Recently three subtypes (alpha 1a, alpha
      1b, and alpha 1d) were cloned. Using probes for these subtypes, we demonstrated
      their expression in the tissues of ten cases of benign prostatic hypertrophy,
      using in situ hybridization. To determine the ratio between these subtypes, an
      RNase protection assay was also performed in three cases. Expression of the alpha
      1a and alpha 1d adrenoceptors was diffuse in the smooth muscles of the
      interstitium, but was absent in glandular epithelial cells. On the contrary, the
      alpha 1b adrenoceptor was hardly detectable. The RNase protection assay confirmed
      the absence of the alpha 1b adrenoceptor, the ratio of alpha 1a and alpha 1d
      being 4:1. These results supported the idea that the differences in prostatic
      contractile response to several adrenergic drugs are based on the affinities of
      these drugs for the different subtypes.

PMID- 8762061
TI  - Distribution of peptidergic nerve fibres in bullfrog lingual papillae
      demonstrated by a combination of double immunofluorescence labelling and a
      multiple dye filter.
AB  - Immunoreactivity of substance P, calcitonin gene-related peptide, vasoactive
      intestinal polypeptide, neuropeptide Y, and galanin is localized in nerve fibres
      distributed in the fungiform and filiform papillae of the tongue of the bullfrog,
      Rana catesbeiana. A combination of indirect double immunofluorescence labelling
      and a multiple dye filter system clearly demonstrated that all substance P fibres
      in the connective tissue core of the fungiform and filiform papillae, and within
      the rim of ciliated cells located on the top of the fungiform papillae showed
      coexistence with calcitonin gene-related peptide. A few fibres in the epithelial
      discs, which are located in the centre of the top of the fungiform papillae,
      showed the immunoreactivity of calcitonin gene-related peptide alone. There were
      no substance P fibres which showed coexistence with vasoactive intestinal
      polypeptide, galanin, and neuropeptide Y. In high magnification images, substance
      P and vasoactive intestinal polypeptide, and substance P and galanin fibres were
      recognized as two intertwined fibres within the same thin nerve bundle. No
      immunoreactivity of leucine- and methionine-enkephalins can be detected. These
      findings suggest that the chemoreceptor function of the bullfrog gustatory organ
      may be under the control of complicated peptidergic innervation.

PMID- 8762062
TI  - Chloride channel blockers decrease intracellular pH in cultured renal epithelial
      LLC-PK1 cells.
AB  - The effects of chloride channel blockers upon intracellular pH (pHi) were
      examined in renal epithelial monolayers of LLC-PK1 cells. A significant
      intracellular acidification was found with addition of 100 microM 5-nitro-2-(3
      phenylpropylamino)-benzoate (NPPB), niflumic acid, flufenamate and diphenylamine
      2-carboxylate (DPC) but not with 4,4'-diisothiocyanatostilbene-2-2'disulphonic
      acid (DIDS). The effects of these agents upon pHi was dose-dependent with
      apparent K0.5 values of: 16.7 +/- 0.3 microM, 34.2 +/- 0.9 microM and 740 +/- 13
      microM for niflumic acid, flufenamate and DPC respectively. The results indicate
      that at concentrations commonly used to block channel activity these chloride
      channel blockers have profound effects upon pHi.

PMID- 8762063
TI  - Potent antagonism by BIM-23056 at the human recombinant somatostatin sst5
      receptor.
AB  - We have investigated the effects of somatostatin (SRIF) and the linear
      octapeptide BIM-23056 on changes in intracellular calcium ion concentration
      ([Ca2+]i) and on the formation of inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) in
      CHO-K1 cells transfected with the human recombinant SRIF sst5 receptor. SRIF
      elicited concentration-dependent increases in [Ca2+]i, with a pEC50 of 7.02 +/-
      0.06, while BIM-23056 (1 x 10(-7) M) behaved not as an agonist but as a potent,
      surmountable antagonist of these increases in [Ca2+]i. The SRIF concentration
      effect curve for increases in [Ca2+]i was shifted rightward producing an
      estimated pKB for the antagonist of 8.0. BIM-23056 (1 x 10(-7) M) also
      significantly attenuated Ins(1,4,5)P3 increases due to SRIF, but had no effect on
      either basal or uridine 5'-triphosphate (UTP) (1 x 10(-4) M) stimulated increases
      in the levels of [Ca2+]i or Ins(1,4,5)P3.

PMID- 8762064
TI  - Comparison of the uptake of [3H]-gabapentin with the uptake of L-[3H]-leucine
      into rat brain synaptosomes.
AB  - 1. Gabapentin is a novel anticonvulsant with an unknown mechanism of action.
      Homogenate binding studies described elsewhere have suggested that [3H]
      gabapentin binds to a site in brain similar to the large neutral amino acid
      (LNAA) uptake site, termed system-L. 2. This study describes an investigation
      into the uptake of [3H]-gabapentin into a crude synaptosomal preparation from
      cerebral cortex of rat brain. Characterization studies showed that [3H]
      gabapentin is taken up into synaptosomes by a system that is similar to that
      responsible for the uptake of L-[3H]-leucine. This system is sodium-independent,
      temperature-sensitive and requires ATP for function. 3. Kinetic studies of [3H]
      gabapentin uptake produced a Michaelis constant (KM = 160 microM) similar to that
      observed for L-[3H]-leucine (KM = 110.3 microM). Vmax values were 837.1 pmol mg-1
      protein min-1 and 2.192 nmol mg-1 protein min-1 respectively. 4. Gabapentin and L
      leucine mutually inhibit their uptake. Lineweaver-Burke plots of these data
      demonstrate that inhibition occurs by a competitive mechanism. Further to this
      the Dixon transformation of the data illustrates that these two substrates share
      a common uptake site by the similarity between their calculated Ki and KM values
      (gabapentin inhibition of L-[3H]-leucine uptake: Ki = 160 microM; L-leucine
      inhibition of [3H]-gabapentin uptake: Ki = 262 microM). 5. Studies into the
      effect of gabapentin, the system-L-specific ligand 2-(-)-endoamino-bicycloheptane
      2-carboxylic acid (BCH), and the system-A-specific ligand alpha-(methyl-amino)
      isobutyric acid (MeAIB), on the initial rate of uptake of [3H]-glycine, L-[3H]
      glutamate, L-[3H]-glutamine, and L-[3H]-leucine were performed. At 100 microM,
      gabapentin significantly inhibited initial rate of uptake of [3H]-glycine (29%),
      L-[3H]-glutamate (22%) and L-[3H]-leucine (40%). 6. Gabapentin is taken up into
      synaptosomes by a system similar to system-L, responsible for the uptake of large
      neutral amino acids. Gabapentin will also inhibit the uptake of certain
      excitatory amino acids in this synaptosomal preparation. The implications of
      these findings for the mechanism of action for gabapentin are unclear. The data
      presented here may suggest an intracellular site for mechanism of action for this
      compound. Similarly changes in levels of amino acid pools may be involved in the
      mechanism of gabapentin's anticonvulsant action.

PMID- 8762065
TI  - Comparison of the autoradiographic binding distribution of [3H]-gabapentin with
      excitatory amino acid receptor and amino acid uptake site distributions in rat
      brain.
AB  - 1. Gabapentin is a novel anticonvulsant with an unknown mechanism of action.
      Recent homogenate binding studies with [3H]-gabapentin have suggested a structure
      activity relationship similar to that shown for the amino acid transport system
      responsible for the uptake of large neutral amino acids (LNAA). 2. The
      autoradiographic binding distribution of [3H]-gabapentin in rat brain was
      compared with the distributions for excitatory amino acid receptor subtypes and
      the uptake sites for excitatory and large neutral amino acids in consecutive rat
      brain sections. 3. Densitometric measurement of the autoradiographic images
      followed by normalisation with respect to the hippocampus CA1 stratum radiatum,
      was carried out before comparison of each binding distribution with that of [3H]
      gabapentin by linear regression analysis. The correlation coefficients observed
      showed no absolute correlation was observed between the binding distributions of
      [3H]-gabapentin and those of the excitatory amino acid receptor subtypes. The
      acidic and large neutral amino acid uptake site distributions demonstrated a much
      closer correlation to the [3H]-gabapentin binding site distribution. The
      correlation coefficients for D-[3H]-aspartate, L-[3H]-leucine and L-[3H]
      isoleucine binding site distributions were 0.76, 0.90 and 0.88 respectively. 4.
      Concentration-dependent inhibition by unlabelled gabapentin of autoradiographic
      binding of L-[3H]-leucine and L-[3H]-isoleucine was observed, with non-specific
      binding levels being reached at concentrations between 10 and 100 microM. 5.
      Excitotoxic quinolinic acid lesion studies in rat brain caudate putamen and
      autoradiography were carried out for the amino acid uptake sites mentioned above.
      The resulting glial infiltration of the lesioned areas was visualized by
      autoradiography using the peripheral benzodiazepine receptor specific ligand [3H]
      PK11195. A significant decrease in binding density in the lesioned area compared
      with sham-operated animals was observed for D-[3H]-aspartate, L-[3H]-leucine, L
      [3H]-isoleucine and [3H]-gabapentin, whilst [3H]-PK11195 showed a significant
      increase in binding density indicative of glial infiltration into the lesioned
      area. These results suggest that the gabapentin binding site and the acidic and
      LNAA uptake site may be present on cell bodies of a neuronal population of cells.
      6. From these studies it appears that [3H]-gabapentin, L-[3H]-leucine and L-[3H]
      isoleucine bind to the same site in rat brain. The inhibition of [3H]-gabapentin
      binding by the LNAA uptake system-specific ligand, BCH, suggests that [3H]
      gabapentin may label this uptake site, termed system-L. Conversely these ligands
      could be labelling a novel site that coincidentally has a similar structure
      activity relationship to this uptake site. These results suggest a novel
      mechanistically relevant site of action for gabapentin and may enable further
      anti-epileptic agents of this type to be developed.

PMID- 8762066
TI  - Relaxation of guinea-pig trachea by sodium nitroprusside: cyclic GMP and nitric
      oxide not involved.
AB  - 1. Sodium nitroprusside (SNP) completely relaxed the guinea-pig isolated,
      perfused trachea in a concentration-dependent manner. Although SNP was less
      potent by about 2 orders of magnitude, its maximal effect was 25% higher compared
      to isoprenaline. 2. SNP (3.2 microM) increased cyclic GMP levels by 300% and
      relaxed guinea-pig isolated, perfused trachea by 54%. The SNP-induced relaxations
      of the preparations were not affected by the guanylate cyclase inhibitor,
      methylene blue. Moreover, zaprinast, a cyclic GMP-specific phosphodiesterase
      inhibitor which was supposed to enhance SNP-induced relaxations, decreased the
      maximal relaxation by 22% (P < 0.001). 3. In contrast, 8Br-cyclic GMP (10 microM)
      increased the cyclic GMP levels by 1100% without inducing a marked relaxation. 4.
      SNP (10 microM) and S-nitroso-N-acetylpenicillamine (SNAP; a direct donor of
      nitric oxide; 10 microM), relaxed the tissues by 75% and 25%, respectively,
      without any nitric oxide (NO) release by SNP (< 1 pmol 100 microliters-1), but a
      substantial NO release by SNAP (560 pmol 100 microliters-1). 5. It is concluded
      that the SNP-induced tracheal relaxations are probably not mediated by cyclic GMP
      and NO.

PMID- 8762067
TI  - Drug-induced in vitro inhibition of neutrophil-endothelial cell adhesion.
AB  - 1. Leukocyte-endothelial cell interactions play an important role during
      ischaemia-reperfusion events. Adhesion molecules are specifically implicated in
      this interaction process. 2. Since defibrotide has been shown to be an efficient
      drug in reducing damage due to ischaemia-reperfusion in many experimental models,
      we analysed the effect of defibrotide in vitro on leukocyte adhesion to
      endothelial cells in basal conditions and after their stimulation. 3. In basal
      conditions, defibrotide (1000 micrograms ml-1) partially inhibited leukocyte
      adhesion to endothelial cells by 17.3% +/- 3.6 (P < 0.05), and after endothelial
      cell stimulation (TNF-alpha, 500 u ml-1) or after leukocyte stimulation (fMLP,
      10(-7) M), it inhibited leukocyte adhesion by 26.5% +/- 3.4 and 32.4% +/- 1.8,
      respectively (P < 0.05). 4. In adhesion blockage experiments, the use of the
      monoclonal antibody anti-CD31 (5 micrograms ml-1) did not demonstrate a
      significant inhibitory effect whereas use of the monoclonal antibody anti-LFA-1
      (5 micrograms ml-1) significantly interfered with the effect of defibrotide. 5.
      This result was confirmed in NIH/3T3-ICAM-1 transfected cells. 6. We conclude
      that defibrotide is able to interfere with leukocyte adhesion to endothelial
      cells mainly in activated conditions and that the ICAM-1/LFA-1 adhesion system is
      involved in the defibrotide mechanism of action.

PMID- 8762068
TI  - VIP-induced relaxation of guinea-pig intestinal smooth muscle cells: sequential
      involvement of cyclic AMP and nitric oxide.
AB  - 1. A possible interaction between cyclic AMP and nitric oxide (NO) in mediating
      the relaxant effect of vasoactive intestinal polypeptide (VIP) on intestinal
      smooth muscle cells has been investigated. The effects of the inhibitor of NO
      synthesis, NG-nitro-L-arginine methyl ester (L-NAME), have been studied on VIP-,
      forskolin-, and 8 bromo-cyclic AMP- induced relaxation of cells, dispersed by
      enzymatic digestion of muscle strips from the circular layer of guinea-pig ileum.
      2. VIP alone did not modify the length of isolated muscle cells. By contrast,
      when the cells were contracted by cholecystokinin octapeptide, CCK8 (10 nM), VIP
      inhibited this contraction, inducing a concentration-dependent relaxation of the
      cells. Maximal relaxation was induced by 1 microM VIP (EC50 = 408.2 +/- 16.7 pM).
      3. N-ethylmaleimide, inhibitors of adenylate cyclase or somatostatin, abolished
      the relaxing effect of VIP. (R)-p-cAMPs, an antagonist of cyclic AMP on protein
      kinase A also inhibited the VIP-induced relaxation by 92.1 +/- 6.3%. Inhibitors
      of nitric oxide synthase (NOS), L-NAME and L-NMMA, partially inhibited VIP
      induced relaxation. The effect of L-NAME was reversed by L-arginine but not by D
      arginine. 4. (R)-p-cAMPS and L-NAME also inhibited the cell relaxation induced
      either by forskolin which directly stimulates adenylate cyclase activity or 8
      bromo-cyclic AMP, an analogue of cyclic AMP. 5. When cells were incubated for 30
      min with dexamethasone 10 microM, a glucocorticoid known to decrease the
      synthesis of iNOS, the relaxing effect of a maximal concentration of VIP was
      decreased by 52 +/- 4% and L-NMMA had no further effect on this residual VIP
      induced relaxation. Milrinone, a phosphodiesterase type III inhibitor,
      potentiated the relaxant effect of VIP. 6. These data demonstrate that the
      intracellular pathway mediating the relaxant effect of VIP in intestinal smooth
      muscle cells includes the sequential activation of adenylate cyclase, protein
      kinase A, activation of NOS and finally production of NO and cyclic GMP. NO could
      in turn regulate the cyclic AMP-dependent pathway of cell relaxation.

PMID- 8762069
TI  - The mechanism of acidic pH-induced contraction in aortae from SHR and WKY rats
      enhanced by increasing blood pressure.
AB  - 1. Effect of pH on vascular smooth muscle contraction was analyzed by use of
      biochemical and pharmacological techniques. 2. In the aorta isolated from
      spontaneously hypertensive rats (SHR) decreasing extracellular pH (pH0) caused a
      rapid acidification of intracellular pH accompanied by a pH0-dependent increase
      in tension. The contraction of the SHR aorta was remarkable compared with that of
      the Wistar Kyoto rat (WKY) aorta. 3. Removal of NH4Cl caused a transient decrease
      in intracellular pH followed by a marked increase in tension. 4. Both contraction
      and intracellular Ca2+ mobilization induced by acidic pH0 were markedly inhibited
      by removal of extracellular Ca2+, verapamil and adenosine, whereas these were not
      affected by tetrodotoxin or Gd3+, a stretch-activated cation channel blocker.
      Furthermore, cromakalim (a K+ channel opener) inhibited acidic pH0-induced
      contraction (APIC). 5. Acidic pH0 induced a depolarization of cultured smooth
      muscle cells from SHR aorta. 6. Blood pressure elevated with increasing age of
      WKY and SHR accompanied by an increase in APIC. Feeding WKY with NG-nitro-L
      arginine, an inhibitor of nitric oxide synthases caused a marked elevation of
      their blood pressure followed by an increase in APIC. 7. These results suggest
      that APIC is caused by Ca2+ influx mediated through the activation of voltage
      sensitive Ca2+ channels mainly due to acidic pH0-induced depolarization of the
      plasma membrane of smooth muscle cells. It is also suggested that APIC is
      strengthened by the elevation of blood pressure.

PMID- 8762070
TI  - Effects of inhalational general anaesthetics on native glycine receptors in rat
      medullary neurones and recombinant glycine receptors in Xenopus oocytes.
AB  - 1. Glycine responses were studied under voltage clamp in Xenopus oocytes injected
      with cDNA encoding mammalian glycine receptor subunits and in rat medullary
      neurones. Bath application of glycine gave strychnine-sensitive currents which
      reversed close to the expected equilibrium potentials for chloride ions. The peak
      currents for the receptors expressed in oocytes fitted a Hill equation with EC50
      = 215 +/- 5 microM and Hill coefficient nH = 1.70 +/- 0.05 (means +/- s.e.
      means). The peak currents from the receptors in medullary neurones fitted a Hill
      equation with EC50 = 30 +/- 1 microM and Hill coefficient nH = 1.76 +/- 0.08. The
      current-voltage relationship for the receptors expressed in oocytes showed strong
      outward rectification (with Vrev = -21 +/- 2 mV), while that for the glycine
      responses from the medullary neurones in symmetrical Cl- was linear (with Vrev =
      3.2 +/- 0.6 mV). 2. Inhalational general anaesthetics, at concentrations close to
      their human minimum alveolar concentrations (MACs), potentiated responses to low
      concentrations of glycine. The potentiation observed with the recombinant
      receptors (between 60-22%) was approximately twice that found with the medullary
      neurones (between 40-80%). For both the recombinant receptors and the receptors
      in medullary neurones, the degree of potentiation increased in the order of
      methoxyflurane approximately sevoflurane < halothane approximately isoflurane
      approximately enflurane. There was no significant difference between the
      potentiations observed for the two optical isomers of isoflurane. 3. For both the
      recombinant and native receptors, isoflurane potentiated the currents in a dose
      dependent manner at low concentrations of glycine, although at high glycine
      concentrations the anaesthetic had no significant effect on the glycine-activated
      responses. The major effect of isoflurane was to cause a parallel leftward shift
      in the glycine concentration-response curves. The glycine EC50 concentration for
      the recombinant receptors decreased from a control value of 215 +/- 5 microM to
      84 +/- 7 microM glycine at 610 microM isoflurane, while that for the medullary
      neurones decreased from a control value of 30 +/- 1 microM to 18 +/- 2 microM
      glycine at the same concentration of isoflurane. The potentiation was independent
      of membrane potential. 4. Isoflurane also potentiated responses to taurine, a
      partial agonist at the glycine receptor. This was observed for receptors
      expressed in oocytes at both low and saturating concentrations of taurine. The
      EC50 concentration decreased from a control value of 1.6 +/- 0.2 to 0.9 +/- 0.1
      mM taurine in the presence of 305 microM isoflurane, while the maximum response
      to taurine increased from 47 +/- 2 to 59 +/- 2% of the maximum response to
      glycine. 5. Glycine receptors, like other members of the fast ligand-gated
      receptor superfamily, are sensitive to clinically relevant concentrations of
      inhalational general anaesthetics. Effects at these receptors may, therefore,
      play some role in the maintenance of the anaesthetic state.

PMID- 8762071
TI  - Mechanical and electrophysiological effects of 8-oxoberberine (JKL1073A) on
      atrial tissue.
AB  - The effects of 8-oxoberberine (JKL1073A) on contractions and electrophysiological
      characteristics of atrial tissues were examined. In driven left atria of the rat
      JKL1073A (10-100 microM) increased twitch tension dose-dependently. In
      spontaneously beating right atria, JKL1073A increased twitch tension but
      decreased beating rate slightly. The positive inotropic and the negative
      chronotropic effect of 30 microM JKL1073A was not affected by prazosin (1
      microM), propranolol (1 microM) and 3-isobutyl-1-methyl-xanthine (10 microM) but
      significantly suppressed by 4-aminopyridine (2 mM 4-AP). Current-clamp study
      revealed that JKL1073A prolonged rat atrial action potential duration (APD). This
      prolongation of APD by JKL1073A was decreased by pretreating the cells with 2 mM
      4-AP. Voltage-clamp study showed that JKL1073A inhibited the integral of the
      transient outward current (I(to)) dose-dependently with a KD value of 3.66 +/-
      0.93 microM in rat atrial myocytes. The equilibrium dissociation constant (Kd)
      for JKL1073A bindings to open state I(to) was 0.50 +/- 0.08 microM. The
      suppression of I(to) by 3 microM JKL1073A was accompanied by shortening of its
      inactivation time constant from 52.5 +/- 0.9 ms to 16.8 +/- 0.7 ms. V(0.5) for
      the steady-state inactivation curve of I(to) was shifted from -25.7 +/- 3.3 mV to
      -34.8 +/- 3.2 mV. In human atrial cells, similar inhibition of I(to) and
      prolongation of APD by JKL1073A was found. The KD value of JKL1073A for
      inhibition of the integral of I(to) in human atrial cells is 4.03 +/- 0.02
      microM. The Kd for bindings to open state I(to) is 0.5 microM. Currents through
      K1 channels of rat and human atrial myocytes were not inhibited by JKL1073A at
      concentrations up to 10 microM. These results indicate that JKL1073A exerts a
      positive inotropic effect by inhibition of I(to). JKL1073A inhibit I(to) by
      binding to open state channels or shifting of the steady-state inactivation curve
      of I(to).

PMID- 8762072
TI  - Activation of potassium currents by inhibitors of calcium-activated chloride
      conductance in rabbit portal vein smooth muscle cells.
AB  - 1. The conventional whole-cell recording technique was used to study the effects
      of the chloride channel inhibitors ethacrynic acid, anthracene-9-carboxylic acid
      (A-9-C) and indanyloxyacetic acid (IAA) on membrane currents in rabbit portal
      vein smooth muscle cells at a holding potential of 0 mV. 2. Using a pipette
      solution that contained 1 x 10(-4) M 1,2-bis (2-aminophenoxy)-ethane-N,N,N,N,
      tetraacetic acid (BAPTA) and a normal bathing solution the addition of ethacrynic
      acid (2 x 10(-4) M to 1 x 10(-3) M) inhibited spontaneous transient outward
      currents (STOCs) and evoked a concentration-dependent current at a holding
      potential of 0 mV. A similar current was activated by IAA (5 x 10(-4) M to 1 x
      10(-3) M) but not by A-9-C (1-5 x 10(-3) M) at a holding potential of 0 mV. 3.
      The amplitude of the current evoked by ethacrynic acid and IAA was linearly
      related to potential between -30 and 0 mV and displayed outward rectification at
      positive potentials. The current induced by A-9-C was evident only at potentials
      positive to +20 mV. 4. Glibenclamide (1 x 10(-5) M) abolished the current evoked
      by ethacrynic acid and IAA at potentials negative to +10 mV and partially
      inhibited the current positive to +10 mV. The glibenclamide-insensitive current
      at positive potentials was completely inhibited by 1 x 10(-3) M TEA. The A-9-C
      evoked current was insensitive to glibenclamide and abolished by 1 x 10(-3) M
      TEA. 5. The glibenclamide-sensitive current activated by ethacrynic acid was not
      sustained and declined to control levels in the continued presence of ethacrynic
      acid. However, the outwardly rectifying current recorded at +50 mV was well
      maintained over the same period. 6. Outwardly rectifying currents evoked by
      ethacrynic acid and A-9-C were observed with a pipette solution containing 1 x
      10(-2) M BAPTA in cells bathed in Ca-free extracellular solution containing 5 x
      10(-4) M BAPTA and 1 x 10(-5) M cyclopiazonic acid. 7. It is concluded that all
      three chloride-channel blockers activated an outwardly rectifying, TEA-sensitive
      current. Moreover, ethacrynic acid and IAA evoked an additional glibenclamide
      sensitive current which was present at all potentials between -30 and +50 mV.

PMID- 8762073
TI  - Rat proteinase-activated receptor-2 (PAR-2): cDNA sequence and activity of
      receptor-derived peptides in gastric and vascular tissue.
AB  - 1. The biological activities of the proteinase-activated receptor number 2 (PAR
      2)-derived peptides, SLIGRL (PP6) SLIGRL-NH2 (PP6-NH2) and SLIGR-NH2 (PP5-NH2)
      were measured in mouse and rat gastric longitudinal muscle (LM) tissue and in a
      rat aortic ring preparation and the actions of the PAR-2-derived peptides were
      compared with trypsin and with the actions of the thrombin receptor activating
      peptide, SFLLR-NH2 (TP5-NH2). 2. From a neonatal rat intestinal cDNA library, and
      from intestinal and kidney-derived cDNA, the coding region of the rat PAR-2
      receptor was cloned and sequenced, thereby establishing its close sequence
      identity with the previously described mouse PAR-2 receptor; and this
      information, along with a reverse-transcriptase (RT) polymerase chain reaction
      (PCR) analysis of cDNA derived from gastric and aortic tissue was used to
      establish the concurrent presence of PAR-2 and thrombin receptor mRNA in both
      tissues. 3. In the mouse and rat gastric preparations, the PAR-2-derived
      polypeptides, PP6, PP6-HN2 and PP5-NH2 caused contractile responses that mimicked
      the contractile actions of low concentrations of trypsin (5 u/ml-1; 10 nM) and
      that were equivalent to contractions caused by TP5-NH2. 4. The cumulative
      exposure of the rat LM tissue to PP6-NH2 led to a desensitization of the
      contractile response to this polypeptide, but not to TP5-NH2 and vice versa, so
      as to indicate a lack of cross-desensitization between the receptors responsive
      to the PAR-2 and thrombin receptor-derived peptides. 5. In the rat gastric
      preparation, the potencies of the PAR-2-activating peptides were lower than the
      potency of TP5-NH2 (potency order: TP5-NH2 > > PP6-NH2 > or = PP6 > PP5-NH2); PP6
      was a partial agonist in this preparation. 6. The contractile actions of PP6 and
      PP6-NH2 in the rat gastric preparation required the presence of extracellular
      calcium, were inhibited by nifedipine and were blocked by the cyclo-oxygenase
      inhibitor, indomethacin and by the tyrosine kinase inhibitor, genistein, but not
      by the kinase C inhibitor, GF109203X. The contractile responses were not blocked
      by atropine, chlorpheniramine, phenoxybenzamine, propranolol, ritanserin or
      tetrodotoxin. 7. In a precontracted rat aortic ring preparation, with an intact
      endothelium, all of the PAR-2-derived peptides caused a prompt relaxation
      response that was blocked by the nitric oxide synthase inhibitor, N omega-nitro-L
      arginine-methyl ester (L-NAME) but not by D-NAME; in an endothelium-free
      preparation, which possessed mRNA for both the PAR-2 and thrombin receptors, the
      PAR-2-activating peptides caused neither a relaxation nor a contraction, in
      contrast with the contractile action of TP5-NH2. The relaxation response to PP6
      NH2 was not blocked by atropine, chlorpheniramine, genistein, indomethacin,
      propranolol or ritanserin. 8. In the rat aortic preparation, the potencies of
      PP6, PP6-NH2 and PP5-NH2 were greater than those of the thrombin receptor
      activating peptide, TP5-NH2 (potency order: PP6-NH2 > or = PP6 > PP5-NH2 > TP5
      NH2). 9. In the rat aortic preparation, the relaxant actions of the PAR-2-derived
      peptides were mimicked by trypsin, at concentrations (0.5-1 u ml-1; 1-2 nM) lower
      than those that can activate the thrombin receptor. 10. The bioassay data
      obtained with the PAR-2 peptides and with trypsin, along with the molecular
      cloning/RT-PCR analysis, point to the presence of functional PAR-2 receptors that
      can activate distinct responses in the gastric and vascular smooth muscle
      preparations. These responses were comparable to those resulting from thrombin
      receptor activation in the same tissues, so as to suggest that the receptor for
      the PAR-2-activating peptides may play a physiological role as far reaching as
      the one proposed for the thrombin receptor.

PMID- 8762074
TI  - Endothelins-induce cyclicAMP formation in the guinea-pig trachea through an ETA
      receptor- and cyclooxygenase-dependent mechanism.
AB  - 1. The non-selective endothelin agonist, endothelin-1 (ET-1), and the selective
      ETB receptor agonist, sarafotoxin-S6c (SRTX-c), contracted guinea-pig isolated
      trachea in a concentration-dependent manner. The EC50 value for ET-1 (11 +/- 2.1
      nM) was significantly higher than that of SRTX-c (3.2 +/- 0.21 nM) and the
      maximal developed tension due to SRTX-c was 42.8 +/- 2.3% higher than that
      produced by ET-1 (P < 0.05). 2. Pretreatment with the ETA antagonist, BQ-610,
      appreciably enhanced the developed tension due to ET-1 but not SRTX-c. Likewise,
      the cyclo-oxygenase inhibitor, indomethacin, markedly potentiated the contractile
      responses to ET-1, but not to SRTX-c. Combining BQ-610 with indomethacin was not
      more effective than either of them in augmenting ET-1-evoked tension. 3. ET-1
      significantly increased cyclic AMP formation in the trachea in concentration- and
      time-dependent manners. A t1/2 value of 4.3 min, an EC50 value of 20 +/- 3 nM and
      a maximal cyclic AMP increment of 124% above the basal level, were obtained for
      ET-1. Similarly but less effectively, ET-3 (0.1 microM) increased cyclic AMP
      level (35 +/- 3.7% compared to 94 +/- 7.8% for the same concentration of ET-1).
      By contrast, SRTX-c did not alter the cyclicAMP level when applied in
      concentrations up to 1 microM. 4. Pre-incubation of the trachea with BQ-610 (1
      microM) or indomethacin (1 microM) prevented cyclicAMP formation by either ET-1
      or ET-3. 5. The results of the present study indicate a negative regulatory role
      mediated by the ETA receptor on the ETB-triggered mechanical response. This
      effect is likely to be mediated by activation of adenylate cyclase through a
      cyclo-oxygenase-dependent mechanism.

PMID- 8762075
TI  - Evidence for two distinct P2-purinoceptors subserving contraction of the rat
      anococcygeus smooth muscle.
AB  - 1. The effects of the P2-purinoceptor agonists, adenosine 5'-triphosphate (ATP),
      alpha, beta-methylene ATP (alpha, beta-MeATP), beta, gamma-methylene ATP (beta,
      gamma-MeATP), L-beta, gamma-methylene ATP (L-beta, gamma-MeATP), adenosine-5'-O
      (2-thiodiphosphate) (ADP beta S), and 2-methylthio ATP (2-MeSATP) were
      investigated on the isometric tension of the rat anococcygeus muscle. 2. Non
      cumulative additions of ATP (100-1500 microM), alpha, beta-MeATP (1-300 microM),
      beta, gamma-MeATP (10-300 microM), L-beta, gamma-MeATP (3-100 microM) and ADP
      beta S (1-100 microM) produced concentration-dependent contractions, whereas 2
      MeSATP (1-100 microM) had no effect. The rank order of potency was alpha, beta
      MeATP > L-beta, gamma-MeATP > or = ADP beta S > beta, gamma-MeATP > > ATP > 2
      MeSATP. 3. Contractions to cumulative additions of ATP, alpha, beta-MeATP, beta,
      gamma-MeATP and L-beta, gamma-MeATP were subject to desensitization whilst those
      to ADP beta S were unaffected. 4. Contractions to ATP, alpha, beta-MeATP, beta,
      gamma-MeATP and ADP beta S were abolished by the non-selective P2X/. P2Y
      purinoceptor antagonist, suramin (100 microM). In contrast, contractions to ATP,
      alpha, beta-MeATP and beta, gamma-MeATP were not affected by the non-selective P1
      purinoceptor antagonist 8-(p-sulphophenyl)-theophylline (8SPT, 30 microM).
      Blockade of P2X-purinoceptors with the selective P2X-purinoceptor antagonist
      pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 10 microM) or
      desensitization with L-beta, gamma-MeATP (10 microM) abolished contractions to
      alpha, beta-MeATP, but enhanced those to ADP beta S. The P2Y-purinoceptor
      antagonist, reactive blue 2 (RB2, 100 microM) enhanced contractions to ATP and
      alpha, beta-MeATP but abolished those to ADP beta S. 5. Simultaneous addition of
      alpha, beta-MeATP and ADP beta S produced an additive contraction. 6. The
      findings suggest that in the rat anococcygeus, smooth muscle cells are endowed
      with two distinct P2-purinoceptors which subserve contractions: a P2X
      purinoceptor activated by ATP and its analogues, and another type of P2
      purinoceptor activated by ADP beta S.

PMID- 8762076
TI  - Dissociation of P2 purinoceptor-mediated increase in intracellular Ca2+ level
      from myosin light chain phosphorylation and contraction in rat aorta.
AB  - 1. The effects of P2 agonists, adenosine-5'-triphosphate (ATP), alpha, beta
      methylene-adenosine-5'-triphosphate (alpha, beta-me-ATP) and adenosine 5-O-(3
      thiotriphosphate) (ATP gamma S), on the intracellular free Ca2+ level ([Ca2+]i),
      myosin light chain (MLC) phosphorylation and force of contraction were examined
      in vascular smooth muscle of rat aorta. 2. ATP (0.1 microM-1 mM), alpha, beta-me
      ATP (0.1-100 microM) and ATP gamma S (1-100 microM) induced transient increases
      followed by sustained increase in [Ca2+]i. The effects of these agonists were
      concentration-dependent. Compared with the effects of a high concentration of KCl
      (17.5-72.4 mM), the contractions induced by these P2 purinoceptor agonists were
      smaller at a given [Ca2+]i. 3. In the absence of extracellular Ca2+ (with 0.5 mM
      EGTA), ATP gamma S (10 microM) induced large transient increase in [Ca2+]i with
      only small contraction in Ca(2+)-free solution. In contrast, alpha, beta-me-ATP
      (10 microM) induced only a very small increase in [Ca2+]i and contraction. 4. ATP
      (1 mM), alpha, beta-me-ATP (10 microM) and ATP gamma S (10 microM), added during
      stimulation with 0.1 microM noradrenaline, induced additional and transient
      increases in [Ca2+]i which were also not associated with contraction. 5. High K+
      (72.4 mM) increased MLC phosphorylation with a similar time course to that of the
      increase in [Ca2+]i (peak phosphorylation was 56% when [Ca2+]i increased to
      100%). In contrast, the time course of the increase in MLC phosphorylation due to
      ATP (1 mM) did not coincide with that of the large increases in [Ca2+]i; MLC
      phosphorylation increased to only 31% when [Ca2+]i increased to 163%. The MLC
      phosphorylation due to alpha, beta-me-ATP (10 microM) and ATP gamma S (10
      microM), measured at peak [Ca2+]i, were only 19% and 14%, respectively,
      irrespective of a large increase in [Ca2+]i (138% and 188%, respectively). 6. The
      absence of a clear relationship between P2-purinoceptor-mediated increase in
      [Ca2+]i (either by Ca2+ influx or Ca2+ release) and MLC phosphorylation or force
      generation appears to imply that elevation in [Ca2+]i does not contribute to
      these responses.

PMID- 8762077
TI  - Effects of an AT1 receptor antagonist, an ACE inhibitor and a calcium channel
      antagonist on cardiac gene expressions in hypertensive rats.
AB  - 1. This study was undertaken to determine whether the AT1 receptor directly
      contributes to hypertension-induced cardiac hypertrophy and gene expressions. 2.
      Stroke-prone spontaneously hypertensive rats (SHRSP) were given orally an AT1,
      receptor antagonist (losartan, 30 mg kg-1 day-1), an angiotensin converting
      enzyme inhibitor (enalapril 10 mg kg-1 day-1), a dihydropyridine calcium channel
      antagonist (amlodipine, 5 mg kg-1 day-1), or vehicle (control), for 8 weeks (from
      16 to 24 weeks of age). The effects of each drug were compared on ventricular
      weight and mRNA levels for myocardial phenotype- and fibrosis-related genes. 3.
      Left ventricular hypertrophy of SHRSP was accompanied by the increase in mRNA
      levels for two foetal phenotypes of contractile proteins (skeletal alpha-actin
      and beta-myosin heavy chain (beta-MHC)), atrial natriuretic polypeptide (ANP),
      transforming growth factor-beta-1 (TGF-beta 1) and collagen, and a decrease in
      mRNA levels for an adult phenotype of contractile protein (alpha-MHC). Thus, the
      left ventricle of SHRSP was characterized by myocardial transition from an adult
      to a foetal phenotype and interstitial fibrosis at the molecular level. 4.
      Although losartan, enalapril and amlodipine lowered blood pressure of SHRSP to a
      comparable degree throughout the treatment, losartan caused regression of left
      ventricular hypertrophy of SHRSP to a greater extent than amlodipine (P < 0.01).
      5. Losartan significantly decreased mRNA levels for skeletal alpha-actin, ANP,
      TGF-beta 1 and collagen types I, III and IV and increased alpha-MHC mRNA in the
      left ventricle of SHRSP. Amlodipine did not alter left ventricular ANP, alpha-MHC
      and collagen types I and IV mRNA levels of SHRSP. 6. The effects of enalapril on
      left ventricular hypertrophy and gene expressions of SHRSP were similar to those
      of losartan, except for the lack of inhibition of collagen type I expression by
      enalapril. 7. Unlike the hypertrophied left ventricle, there was no significant
      difference between losartan and amlodipine in the effects on non-hypertrophied
      right ventricular gene expressions of SHRSP. 8. Our results show that
      hypertension causes not only left ventricular hypertrophy but also molecular
      transition of myocardium to a foetal phenotype and interstitial fibrosis-related
      molecular changes. These hypertension-induced left ventricular molecular changes
      may be at least in part mediated by the direct action of local angiotensin II via
      the AT1, receptor.

PMID- 8762078
TI  - Stimulation of sodium pump by vasoactive intestinal peptide in guinea-pig
      isolated trachea: potential contribution to mechanisms underlying relaxation of
      smooth muscle.
AB  - 1. Relaxation of airway smooth muscle induced by vasoactive intestinal peptide
      (VIP) is mediated by adenosine 3':5' cyclic monophosphate (cyclic AMP). An
      interaction between the synthesis of cyclic AMP and enzymic activity of the
      plasmalemmal sodium pump (Na(+)-K(+)-ATPase) exists in certain isolated cell
      systems. This study sought to determine the contribution of Na(+)-K(+)-ATPase
      activity to relaxation of airway smooth muscle evoked by VIP. 2. All experiments
      were performed on isolated strips of guinea-pig trachea from which the epithelium
      had been removed. VIP was a more potent relaxant in tissues that were contracted
      with carbachol than those contracted with an equi-effective depolarizing
      concentration of K+. 3. Ouabain (0.1 microM-10 microM) induced contraction of
      tracheal strips. Contraction to ouabain (5 microM) was abolished following
      incubation of tissues with K(+)-free, or Ca(2+)-free (+ EGTA, 0.1 mM)
      physiological solutions. The contractile response to ouabain (5 microM) was not
      influenced significantly by exposure of the tissues to atropine (1 microM),
      phentolamine (5 microM) and diphenhydramine (1 microM) for 60 min. 4. Tissues
      were incubated with ouabain (5 microM; 60 min) or K(+)-free physiological
      solution (60 min) to inhibit Na(+)-K(+)-ATPase activity. These procedures reduced
      relaxation induced by VIP, peptide histidine isoleucine, forskolin, isoprenaline
      and sodium nitroprusside. 5. Relaxation to VIP was impaired significantly
      following exposure of tissues to a low Na+ solution (30 min) or amiloride (500
      microM; 30 min). 6. Ouabain-sensitive uptake of 86Rb was measured in tracheal
      strips (devoid of epithelium and cartilage) as an index of Na(+)-K(+)-ATPase
      activity. VIP (1 microM; 2 min) caused a 4.7 fold stimulation of ouabain
      sensitive uptake of 86Rb. This effect was impaired significantly by low Na+
      solution. 7. The results suggest that (i) relaxation of tracheal smooth muscle to
      VIP is sensitive to procedures that inhibit activity of Na(+)-K(+)-ATPase and
      invoke a role for altered sodium pump function in the mechanisms that underlie
      cyclic AMP-dependent relaxation; and (ii) VIP stimulates ouabain-sensitive uptake
      of 86Rb in airway smooth muscle in a Na(+)-dependent manner.

PMID- 8762079
TI  - Interaction of positive allosteric modulators with human and Drosophila
      recombinant GABA receptors expressed in Xenopus laevis oocytes.
AB  - 1. A comparative study of the actions of structurally diverse allosteric
      modulators on mammalian (human alpha 3 beta 2 gamma 2L) or invertebrate
      (Drosophila melanogaster Rdl or a splice variant of Rdl) recombinant GABA
      receptors has been made using the Xenopus laevis oocyte expression system and the
      two electrode voltage-clamp technique. 2. Oocytes preinjected with the
      appropriate cRNAs responded to bath applied GABA with a concentration-dependent
      inward current. EC50 values of 102 +/- 18 microM; 152 +/- 10 microM and 9.8 +/-
      1.7 microM were determined for human alpha 3, beta 1 gamma 2L, Rdl splice variant
      and the Rdl receptors respectively. 3. Pentobarbitone enhanced GABA-evoked
      currents mediated by either the mammalian or invertebrate receptors. Utilizing
      the appropriate GABA EC10, the EC50 for potentiation was estimated to be 45 +/- 1
      microM, 312 +/- 8 microM and 837 +/- 25 microM for human alpha 3, beta 1 gamma
      2L, Rdl splice variant and Rdl receptors respectively. Maximal enhancement
      (expressed relative to the current induced by the EC10 concentration of GABA
      where this latter response = 1) at the mammalian receptor (10.2 +/- 1 fold) was
      greater that at either the Rdl splice variant (5.5 +/- 1.3 fold) or Rdl (7.9 +/-
      0.8 fold) receptors. 4. Pentobarbitone directly activated the human alpha 3 beta
      1 gamma 2L receptor with an EC50 of 1.2 +/- 0.03 mM and had a maximal effect
      amounting to 3.3 +/- 0.4 fold of the response evoked by the EC10 concentration of
      GABA. Currents evoked by pentobarbitone were blocked by 10-30 microM picrotoxin
      and potentiated by 0.3 microM flunitrazepam. Pentobarbitone did not directly
      activate the invertebrate GABA receptors. 5. 5 alpha-Pregnan-3 alpha-ol-20-one
      potentiated GABA-evoked currents mediated by the human alpha 3 beta 1 gamma 2L
      receptor with an EC50 of 87 +/- 3 nM and a maximal enhancement of 6.7 +/- 0.8
      fold of that produced by the GABA EC10 concentration. By contrast, relatively
      high concentrations (3-10 microM) of this steroid had only a modest effect on the
      Rdl receptor and its splice variant. 6. A small direct effect of 5 alpha-pregnan
      3 alpha-ol-20-one (0.3-10 microM) was detected for the human alpha 3 beta 1 gamma
      2L receptor (maximal effect only 0.08 +/- 0.01 times that of the GABA EC10). This
      response was antagonized by 30 microM picrotoxin and enhanced by flunitrazepam
      (0.3 microM). 5 alpha-Pregnan-3 alpha-ol-20-one did not directly activate the
      invertebrate GABA receptors. 7. Propofol enhanced GABA-evoked currents mediated
      by human alpha 3 beta 1 gamma 2L and Rdl splice variant receptors with EC50
      values of 3.5 +/- 0.1 microM and 8 +/- 0.3 microM respectively. The maximal
      enhancement was similar at the two receptor types (human 11 +/- 1.8 fold;
      invertebrate 8.8 +/- 1.4 fold that of the GABA EC10). 8. Propofol directly
      activated the human alpha 3 beta 1 gamma 2L receptor with an EC50 of 129 +/- 10
      microM, and at a maximally effective concentration, evoked a current amounting to
      3.5 +/- 0.5 times that elicited by a concentration of GABA producing 10% of the
      maximal response. The response to propofol was blocked by 10-30 microM picrotoxin
      and enhanced by flunitrazepam (0.3 microM). Propofol did not directly activate
      the invertebrate Rdl splice variant receptor. 9. GABA-evoked currents mediated by
      the human alpha 3 beta 1 gamma 2L receptor were potentiated by etomidate (EC50 =
      7.7 +/- 0.2 microM) and maximally enhanced to 8 +/- 0.8 fold of the response to
      an EC10 concentration of GABA. By contrast, the Rdl, or Rdl splice variant forms
      of the invertebrate GABA receptor were insensitive to the positive allosteric
      modulating actions of etomidate. Neither the mammalian nor the invertebrate
      receptors, were directly activated by etomidate. 10. delta-Hexachlorocyclohexane
      enhanced GABA-evoked currents with EC50 values of 3.4 +/- 0.1 microM and 3.0 +/-
      0.1 microM for the human alpha 3 beta 1 gamma 2L receptor and the Rdl splice
      variant receptor respectively. The maximal enhancement was 4.5

PMID- 8762080
TI  - Frequency-dependent inhibition of neuronal activity by lappaconitine in normal
      and epileptic hippocampal slices.
AB  - 1. Extracellular recording of the stimulus-evoked population spike in the CA1
      region of rat hippocampal slices in vitro was performed in order to investigate
      whether lappaconitine affects neuronal excitability. Lappaconitine is a diterpene
      alkaloid of plants of the Aconitum genus and has analgesic properties. 2. The
      results reveal an inhibitory action of lappaconitine (10 microM) manifested in a
      slow attenuation of the orthodromic and antidromic population spike. 3. The
      lappaconitine-induced inhibitory action was activity-dependent, that is, it was
      potentiated when frequency of electrical stimulation was increased. In contrast,
      washout of the neurotoxin was accelerated when stimulation frequency was
      decreased. 4. The activity-dependent action of lappaconitine raised the question
      of whether the drug is effective in suppressing the aberrant neuronal activity
      that occurs during an epileptic seizure. The results obtained from experiments on
      epileptic hippocampal slices demonstrated a selective reduction of the later
      spikes in the bursts with less effect on normal neuronal activity. 5. These data
      support the conclusion that lappaconitine, in addition to its antinociceptive
      effect, also has antiepileptic potency due to its highly activity-dependent mode
      of action.

PMID- 8762081
TI  - The effect of dopamine D1 receptor stimulation on the up-regulation of histamine
      H3-receptors following destruction of the ascending dopaminergic neurones.
AB  - 1. The binding of [3H]-(R)alpha-methylhistamine and [3H]-N alpha-methylhistamine
      to histamine H3-receptors, [3H]-SCH23390 to dopamine D1-receptors, and [3H]
      YM09151-2 to dopamine D2-receptors was investigated by quantitative receptor
      autoradiography in the rat brain following 6-hydroxydopamine injection into the
      substantia nigra. 2. The levels of [3H]-(R)alpha-methylhistamine binding sites in
      the denervated striatum and substantia nigra were significantly higher than those
      in the contralateral side from 1 week to 12 weeks after nigral lesions. The H3
      receptor binding was maximal at 3 weeks after nigral lesions and maintained until
      12 weeks. 3. The increased number of histamine H3-receptors was decreased to the
      level of the contralateral side by chronic treatment with a selective dopamine D1
      agonist, SKF38393, but not modified by a selective dopamine D2 agonist,
      quinpirole. 4. Dopamine D1- and D2-receptors in the striatum were similarly up
      regulated after unilateral nigral lesion. On the other hand, the number of
      dopamine D2-receptors in the substantia nigra was markedly decreased after
      administration of 6-hydroxydopamine. 5. The treatment with (S)alpha
      fluoromethylhistidine increased the H3-receptor binding in both the ipsilateral
      and contralateral sides. As a result, the magnitude of the ratio of the H3
      receptor binding between ipsilateral and contralateral sides was partially
      attenuated by treatment with (S)-alpha-fluoromethylhistidine. 6. These results
      strongly suggest that the expression of histamine H3-receptors in the striatum
      and substantia nigra is influenced through D1-receptors by tonic nigrostriatal
      dopaminergic inputs.

PMID- 8762082
TI  - Exogenous pulmonary surfactant as a drug delivering agent: influence of
      antibiotics on surfactant activity.
AB  - 1. It has been proposed to use exogenous pulmonary surfactant as a drug delivery
      system for antibiotics to the alveolar compartment of the lung. Little, however,
      is known about interactions between pulmonary surfactant and antimicrobial
      agents. This study investigated the activity of a bovine pulmonary surfactant
      after mixture with amphotericin B, amoxicillin, ceftazidime, pentamidine or
      tobramycin. 2. Surfactant (1 mg ml-1 in vitro and 40 mg ml-1 in vivo) was mixed
      with 0.375 mg ml-1 amphotericin B, 50 mg ml-1 amoxicillin, 37.5 mg ml-1
      ceftazidime, 1 mg ml-1 pentamidine and 2.5 mg ml-1 tobramycin. Minimal surface
      tension of 50 microliters of the mixtures was measured in vitro by use of the
      Wilhelmy balance. In vivo surfactant activity was evaluated by its capacity to
      restore gas exchange in an established rat model for surfactant deficiency. 3.
      Surfactant deficiency was induced in ventilated rats by repeated lavage of the
      lung with warm saline until PaO2 dropped below 80 cmH2O with 100% inspired oxygen
      at standard ventilation settings. Subsequently an antibiotic-surfactant mixture,
      saline, air, or surfactant alone was instilled intratracheally (4 ml kg-1 volume,
      n = 6 per treatment) and blood gas values were measured 5, 30, 60, 90 and 120 min
      after instillation. 4. The results showed that minimal surface tensions of the
      mixtures were comparable to that of surfactant alone. In vivo PaO2 levels in the
      animals receiving ceftazidime-surfactant or pentamidine-surfactant were unchanged
      when compared to the surfactant group. PaO2 levels in animals receiving
      amphotericin B-surfactant, amoxicillin-surfactant or tobramycin-surfactant were
      significantly decreased compared to the surfactant group. For tobramycin it was
      further found that PaO2 levels were not affected when 0.2 M NaHCO3 (pH = 8.3)
      buffer was used for suspending surfactant instead of saline. 5. It is concluded
      that some antibiotics affect the in vivo activity of a bovine pulmonary
      surfactant. Therefore, before using surfactant-antibiotic mixtures in clinical
      trials, interactions between the two agents should be carefully evaluated.

PMID- 8762083
TI  - Effects of hydroxyethylrutosides on hypoxia-induced activation of human
      endothelial cells in vitro.
AB  - 1. A clinically available mixture of hydroxyethylrutosides (HR) was examined as
      inhibitors of endothelial cell activation by hypoxia in vitro. Thus, the effects
      of HR on ATP depletion, phospholipase A2 activation and neutrophil adherence were
      investigated in hypoxia-activated human umbilical vein endothelial cells in
      primary cell culture. 2. Our results show that HR inhibited two important steps
      of the activation of endothelial cells by hypoxia: the decrease in ATP content,
      which is the starting point of the process, and the activation of phospholipase
      A2 one enzyme responsible for the release of inflammatory mediators. This
      inhibition was dose-dependent with 70 to 90% inhibition at 500 micrograms ml-1 of
      HR. 3. In addition, hypoxia-activated endothelial cells increased their
      adhesiveness for neutrophils. This process could also be prevented in a dose
      dependent manner if endothelial cells were incubated in the presence of HR. This
      inhibition was confirmed by a morphological study. 4. In conclusion, the results
      of this study suggest that a possible explanation for the improvement in venous
      insufficiency by HR observed clinically could be their ability to inhibit the
      activation of endothelial cells during blood stasis.

PMID- 8762084
TI  - Measurement of lipocortin 1 levels in murine peripheral blood leukocytes by flow
      cytometry: modulation by glucocorticoids and inflammation.
AB  - 1. Lipocortin 1 (LC1) immunoreactivity in murine peripheral blood leukocytes was
      quantified by use of a flow cytometric technique associated with a
      permeabilisation protocol with saponin. Using specific antisera raised against
      the whole protein or against its N-terminus peptide, cell-associated LC1-like
      immunoreactivity was easily detected in circulating neutrophils and monocytes,
      whereas very low levels were found in lymphocytes. Of the total protein measured
      17.6% and 36% were associated with the external plasma membrane in neutrophils
      and monocytes, as assessed in the absence of cell permeabilisation, whereas no
      signal was detected on lymphocyte plasma membrane. 2. Treatment of mice with
      dexamethasone (Dex; 0.5-5 micrograms per mouse corresponding to approximately
      0.015-1.5 mg kg-1) increased LC1 levels in neutrophils and monocytes. The 2-3
      fold increase in LC1 levels was time-dependent with a peak at 2 h. Treatment of
      mice with the steroid antagonist, RU486 (two doses of 20 mg kg-1 orally)
      decreased LC1-like immunoreactivity in all three types of circulating leukocytes
      by > or = 50%. 3. Extravasation of blood neutrophils into inflamed tissue sites
      resulted in a consistent reduction (> or = 50%) in LC1 levels compared with
      circulating neutrophils. A high LC1-like immunoreactivity was also measured in
      resident macrophages, of which approximately one third was membrane-associated.
      Induction of an acute inflammatory response in the murine peritoneal cavity did
      not modify total LC1 levels measured in macrophages, but reduced membrane
      associated LC1 to a significant extent, i.e. up to 70%. 4. In conclusion, flow
      cytometric analysis is a rapid and convenient method for detecting and measuring
      LC1 in murine leukocytes. We confirmed that LC1 protein expression is controlled
      by exogenous and endogenous glucocorticoids. Amongst other factor(s) influencing
      protein concentrations, extravasation was found to be associated with a reduced
      LC1 expression in the emigrated cells.

PMID- 8762085
TI  - Regulation of cytosolic calcium in skeletal muscle cells of the mdx mouse under
      conditions of stress.
AB  - 1. In Duchenne muscular dystrophy (DMD) dysregulation of cytosolic calcium
      appears to be involved in the degeneration of skeletal muscle fibres. Therefore,
      we have studied the regulation of the free cytosolic calcium concentration
      ([Ca2+]c) under specific stress conditions in cultured myotubes isolated from the
      hind limbs of wild-type (C57BL10) and dystrophin-deficient mutant mdx mice.
      [Ca2+]c in the myotubes was estimated by the use of the Ca(2+)-sensitive
      fluorescent dye, fura-2. 2. Resting [Ca2+]c was similar in mdx and normal
      myotubes (35 +/- 9 nM and 38 +/- 11 nM, respectively). However, when mdx myotubes
      were exposed to a high extracellular calcium concentration ([Ca2+]c) of 40 mM,
      the [Ca2+]c was elevated to 84 +/- 29 nM, compared to 49 +/- 7 nM in normal
      myotubes. 3. Lowering the osmolarity of the superfusion solution from 300 mOsm to
      100 mOsm resulted also in a rise in [Ca2+]c which was about two times higher for
      mdx (243 +/- 65 nM) than for C57BL10 (135 +/- 37 nM). Replacing extracellular
      Ca2+ by EGTA (0.2 mM) prevented the rise in [Ca2+]c in both mdx and normal
      myotubes when exposed to the low osmolarity solution. 4. Gadolinium ion (50
      microM), an inhibitor of Ca2+ entry, antagonized the rise in [Ca2+]c of myotubes
      superfused with 40 mM [Ca2+]c by 20-40% for both mdx and C57BL10 cells, but did
      not significantly reduce the rise in [Ca2+]c when the cells were exposed to the
      hypo-osmotic buffer (100 mOsm). 5. Incubation of the cell culture for 3-5 days
      from the onset of induction of myotube formation with the membrane permeable
      protease inhibitor, calpeptin (50 microM) abolished the rise in [Ca2+]c in mdx
      myotubes upon exposure to hypo-osmotic shock. 6. Treatment of the cell culture
      for 3-5 days with alpha-methylprednisolone (PDN, 10 microM) attenuated the rise
      in [Ca2+]c following hypo-osmotic stress for both normal and mdx myotubes by
      about 50%. 7. The results described here suggest an increased permeability of mdx
      myotubes to Ca2+ under specific stress conditions. The ameliorating effect of PDN
      on [Ca2+]c could explain, at least partly, the beneficial effect of this drug on
      DMD patients.

PMID- 8762086
TI  - Bosentan-improved cardiopulmonary vascular performance and increased plasma
      levels of endothelin-1 in porcine endotoxin shock.
AB  - 1. To evaluate the possible contribution of endothelin-1 (ET-1) to the
      pathophysiology of porcine septic shock, the non-peptide, mixed ET-receptor
      antagonist, bosentan (RO 47-0203) was administered (5 mg kg-1, i.v.) 30 min
      before infusion of lipopolysaccharide (LPS) (E. coli., serotype 0111:B4) (15
      micrograms kg-1 h-1) and at 3.5 h of endotoxaemia in six anaesthetized and
      mechanically ventilated pigs. Six other pigs served as controls and received only
      LPS infusion. Pulmonary and systemic haemodynamics as well as splenic, renal and
      intestinal blood flows were measured continuously. Release and synthesis of ET-1
      and Big ET-1 were also measured. 2. Only three of the six pigs in the control
      group survived 3 h of LPS infusion while in the bosentantreated group all six
      pigs were alive at that time. A biphasic increase in mean pulmonary arterial
      pressure (MPAP) and pulmonary vascular resistance (PVR) was seen in control pigs.
      Pretreatment with bosentan did not influence the first peak but markedly
      attenuated the second, more prolonged increase in MPAP and PVR. The second dose
      of bosentan completely restored these parameters to pre-LPS levels. The LPS
      induced changes in mean arterial blood pressure, heart rate and systemic vascular
      resistance were similar in both groups, while cardiac output (CO) was
      significantly higher in the bosentan-treated group. The second bosentan dose
      increased CO and splenic and intestinal blood flow without further lowering of
      blood pressure. 3. Bosentan caused an increase of the basal arterial plasma
      levels of ET-1-like immunoreactivity (LI), from 16.8 +/- 1.3 pM to 49.6 +/- 10.0
      pM (n = 6, P < 0.01). However, the rate of the increase of ET-1 levels during the
      LPS infusion was not affected by bosentan. Repeated administration of bosentan
      during LPS infusion caused an additional increase of ET-1-LI levels. Neither the
      basal levels of Big ET-LI nor the LPS induced 8 fold increase in Big ET-LI were
      changed by bosentan. The level of preproET-1 mRNA in the lung was increased about
      3 fold after 4.5 h of LPS treatment. This elevation was not influenced by
      bosentan. 4. From these studies using bosentan, a non-peptide, selective and
      mixed ET-receptor antagonist, we conclude that during LPS-induced shock bosentan
      can abolish the late phase pulmonary hypertension and improve cardiac output as
      well as increase blood flow to the splenic and intestinal vascular beds without
      causing a further decrease in mean arterial blood pressure. Further
      investigations in the clinical setting are needed to evaluate the use of ET
      receptor antagonists, such as bosentan, in treatment of septic shock.

PMID- 8762087
TI  - The effect of forskolin on 5-HT1-like and angiotensin II-induced vasoconstriction
      and cyclic AMP content of the rabbit isolated femoral artery.
AB  - 1. A characteristic feature of vasoconstrictor 5-HT1-like receptors in vitro is
      that responses mediated by these receptors are enhanced by other vasoconstrictor
      agents. In the present study, we have examined the influence of cellular cyclic
      AMP on vasoconstrictor responses to activation of 5-HT1-like receptors in
      isolated ring segments of the rabbit femoral artery (RbFA), and determined
      whether modulation of this second messenger underlies the ability of angiotensin
      II, an endogenous vasoconstrictor, to enhance 5-HT1-like responses. 2. In the
      presence of 0.1 microM ketanserin (to antagonize 5-HT2-receptors) and 0.3 microM
      prazosin (to antagonize alpha 1-adrenoceptors), 5-HT produced a concentration
      related contraction, which was significantly augmented by pre-contraction of the
      vessel with 0.1-0.45 nM ([A30]) angiotensin II. Responses to 5-HT in the presence
      of angiotensin II were inhibited by the 5-HT1-like/5-HT2 antagonist, metergoline
      (1 microM). 3. The directly-acting adenylyl cyclase activator, forskolin (1
      microM), abolished responses to angiotensin II and caused a rightward shift and
      concomitant depression of the 5-HT concentration-effect (E/[A]) curve. Higher
      concentrations of forskolin (> 10 microM) abolished responses to 5-HT and 1
      microM sodium nitroprusside abolished responses to 5-HT and angiotensin II (n =
      7). 4. In the presence of angiotensin II (0.1-0.45 nM), however, 1 microM
      forskolin failed to inhibit 5-HT-induced contractions; the E/A curve for 5-HT (in
      the presence of forskolin and angiotensin II) was not significantly different
      from that produced in the presence of angiotensin II alone. Similarly, the
      presence of angiotensin II (0.1-0.45 nM) was also able to overcome partially the
      inhibitory effect of 1 microM sodium nitroprusside against 5-HT-induced
      contractions (n = 7). In marked contrast, 5-HT failed to elicit a contraction in
      the presence of angiotensin II and 10 microM forskolin (n = 5). 5. 5-HT (1
      microM) significantly reduced basal cyclic AMP accumulation by 35%, whereas
      angiotensin II (0.45 nM) was without effect. The combination of angiotensin II
      and 5-HT failed to alter significantly the reduction in cyclic AMP produced by 5
      HT alone. Forskolin (1 microM) increased cyclic AMP levels 7 fold above basal,
      but neither 1 microM 5-HT nor a combination of 1 microM 5-HT and 0.45 nM
      angiotensin II produced a significant decrease in cyclic AMP content. 6. Whilst
      moderate concentrations of forskolin can inhibit the responses to either agent,
      simultaneous activation of angiotensin II and 5-HT1-like receptors can overcome
      the inhibitory effect of elevated levels of cyclic AMP. Since the potentiating
      effect of angiotensin II, in either the presence or absence of forskolin, occurs
      without significant alteration of cellular cyclic AMP, it seems likely that a
      cyclic AMP-independent pathway is implicated in the synergistic interaction
      between angiotensin II and vasoconstrictor 5-HT1-like receptors.

PMID- 8762088
TI  - Activation by levcromakalim and metabolic inhibition of glibenclamide-sensitive K
      channels in smooth muscle cells of pig proximal urethra.
AB  - 1. The effects of levcromakalim (BRL 38227) on ionic currents recorded from pig
      proximal urethra were investigated by use of tension measurement and patch clamp
      techniques (conventional whole-cell configuration, nystatin perforated patch, and
      cell-attached configuration). 2. Levcromakalim (1 microM) caused a relaxation in
      the resting tone. This levcromakalim-induced relaxation was inhibited by the
      pretreatment with 1 microM glibenclamide. 3. The resting membrane potential
      recorded from single cells in current-clamp mode was-36.1 +/- 4.4 mV (n = 5). 4.
      Levcromakalim induced a concentration-dependent hyperpolarization with a maximum
      (at > or = 10 microM) close to the theoretical equilibrium potential of potassium
      (EK). The membrane hyperpolarization caused by 1 microM levcromakalim (24.7 +/-
      5.8 mV, n = 4) was abolished by 1 microM glibenclamide. 5. Levcromakalim (100
      microM) caused an outward K current in whole-cell recordings which was unaffected
      by iberiotoxin (300 nM) but abolished by glibenclamide (10 microM). 6. In cell
      attached patches, levcromakalim activated a 43 pS K channel which was inhibited
      by the application of glibenclamide. 7. The metabolic poison, cyanide (CN), also
      activated a 43 pS K channel which was suppressed by the application of 10 microM
      glibenclamide. 8. These results indicate that levcromakalim and metabolic
      inhibition activate the same 43 pS K channel in pig proximal urethra. The
      resultant urethral hyperpolarization might reduce the usefulness of K channel
      openers in the treatment of detrusor instability, but be of value in treating
      outflow obstruction.

PMID- 8762089
TI  - Reciprocal inhibition of nitric oxide and prostacyclin synthesis in human
      saphenous vein.
AB  - 1. Angiotensin II (AII) causes contraction of isolated rings of human saphenous
      vein, responses that are attenuated by the presence of functional endothelium. In
      this study, we have investigated the mechanisms controlling the release by AII of
      two endothelial-derived vasorelaxants, prostacyclin (PGI2) and nitric oxide (NO).
      2. Myotropic and biochemical changes were measured in response to AII. The
      biochemical responses measured were the output of PGI2 (as 6-oxo-PGF1 alpha) and
      of NO (as cyclic GMP). Inhibitors of cyclo-oxygenase (COX; piroxicam) or NO
      synthase (NOS; L-NAME), were added to the system to determine the influence of
      endogenous prostaglandins and NO on both myotropic and biochemical responses.
      Furthermore, to mimic the effects of endogenous, PGI2 or NO, exogenous forms of
      these relaxants were added, during inhibition of their endogenous release. 3.
      Contractions of the rings of saphenous vein in response to AII (1-100 nM) were
      unaffected by treatment with either piroxicam (5 microM) or L-NAME (200 microM)
      individually. However, when these two inhibitors were used together, there was an
      increase in the contractions in response to AII. 4. Biochemical analyses revealed
      that during stimulation by AII, levels of PGI2 and NO were enhanced when
      synthesis of the other vasodilator was inhibited, suggesting that endogenous NO
      inhibits PGI2 synthesis and endogenous, PGI2 or another vasorelaxant PG can
      inhibit NO synthesis. 5. Exogenous PGI2 (as iloprost) or NO (from glyceryl
      trinitrate) inhibited the increased output of endogenous NO or PGI2 respectively.
      6. These results demonstrate the presence, in human saphenous vein, of a
      mechanism which ensures that levels of vasodilatation are maintained through a
      compensatory increase in one relaxant agonist when output of the other is
      decreased. If present in vivo such a mechanism would be important in maintaining
      saphenous vein graft patency as both PGI2 and NO are not only vasodilators, but
      inhibit platelet aggregation and myoinitimal hyperplasia, processes implicated in
      degeneration of graft function.

PMID- 8762090
TI  - Evidence that cyclic AMP phosphodiesterase inhibitors suppress TNF alpha
      generation from human monocytes by interacting with a 'low-affinity'
      phosphodiesterase 4 conformer.
AB  - 1. We have investigated the inhibitory effects of RP 73401 (piclamilast) and
      rolipram against human monocyte cyclic AMP-specific phosphodiesterase (PDE4) in
      relation to their effects on prostaglandin (PG)E2-induced cyclic AMP accumulation
      and lipopolysaccharide (LPS)-induced TNF alpha production and TNF alpha mRNA
      expression. 2. PDE4 was found to be the predominant PDE isoenzyme in the
      cytosolic fraction of human monocytes. Cyclic GMP-inhibited PDE (PDE3) was also
      detected in the cytosolic and particulate fractions. Reverse transcription
      polymerase chain reaction (RT-PCR) of human monocyte poly (A+) mRNA revealed
      amplified products corresponding to PDE4 subtypes A and B of which the former was
      most highly expressed. A faint band corresponding in size to PDE4D was also
      observed. 3. RP 73401 was a potent inhibitor of cytosolic PDE4 (IC50: 1.5 +/- 0.6
      nM, n = 3). (+/-)-Rolipram (IC50: 313 +/- 6.7 nM, n = 3) was at least 200 fold
      less potent than RP 73401. R-(-)-rolipram was approximately 3 fold more potent
      than S-(+)-rolipram against cytosolic PDE4. 4. RP 73401 (IC50: 9.2 +/- 2.1 nM, n
      = 6) was over 50 fold more potent than (+/-)-rolipram (IC50: 503 +/- 134 nM, n =
      6) ) in potentiating PGE2-induced cyclic AMP accumulation. R-(-)-rolipram (IC50:
      289 +/- 121 nM, n = 5) was 4.7 fold more potent than its S-(+)-enantiomer (IC50:
      1356 +/- 314 nM, n = 5). A strong and highly-significant, linear correlation (r =
      0.95, P < 0.01, n = 13) was observed between the inhibitory potencies of a range
      of structurally distinct PDE4 inhibitors against monocyte PDE4 and their ED50
      values in enhancing monocyte cyclic AMP accumulation. A poorer, though still
      significant, linear correlation (r = 0.67, P < 0.01, n = 13) was observed between
      the potencies of the same compounds in potentiating PGE2-induced monocyte cyclic
      AMP accumulation and their abilities to displace [3H]-rolipram binding to brain
      membranes. 5. RP 73401 (IC50: 6.9 +/- 3.3 nM, n = 5) was 71 fold more potent than
      (+/-)-rolipram (IC50: 490 +/- 260 nM, n = 4) in inhibiting LPS-induced TNF alpha
      release from monocytes. R-(-)-rolipram (IC50: 397 +/- 178 nM, n = 3) was 5.2-fold
      more potent than its S-(+)- enantiomer (IC50: 2067 +/- 659 nM, n = 3). As with
      cyclic AMP, accumulation a closer, linear correlation existed between the potency
      of structurally distinct compounds in suppressing TNF alpha with PDE4 inhibition
      (r = 0.93, P < 0.01, n = 13) than with displacement of [3H]-rolipram binding (r =
      0.65, P < 0.01, n = 13). 6. RP 73401 (IC50: 2 nM) was 180 fold more potent than
      rolipram (IC50: 360 nM) in suppressing LPS (10 ng ml-1)-induced TNF alpha mRNA.
      7. The results demonstrate that RP 73401 is a very potent inhibitor of TNF alpha
      release from human monocytes suggesting that it may have therapeutic potential in
      the many pathological conditions associated with over-production of this pro
      inflammatory cytokine. Furthermore, PDE inhibitor actions on functional responses
      are better correlated with inhibition of PDE4 catalytic activity than
      displacement of [3H]-rolipram from its high-affinity binding site, suggesting
      that the native PDE4 in human monocytes exists predominantly in a 'low-affinity'
      state.

PMID- 8762091
TI  - Action of the calcium channel blocker lacidipine on cardiac hypertrophy and
      endothelin-1 gene expression in stroke-prone hypertensive rats.
AB  - 1. The tissue-protective effects of calcium channel blockers in hypertension are
      not well dissociated from their effect on systolic blood pressure (SBP). We have
      previously shown that lacidipine, a dihydropyridine-type calcium antagonist,
      reduced the cardiac hypertrophy and the cardiac endothelin-1 (ET-1) gene
      overexpression occurring in salt-loaded stroke-prone spontaneously hypertensive
      rats (SL-SHRSP), an effect occurring without systolic blood pressure (SBP)
      change. In the present study, we have examined whether this action was dose
      related and if it could be associated with ET receptor changes. The action of
      lacidipine was also examined in control SHRSP and in Wistar Kyoto rats (WKY). 2.
      The daily dose of 0.3 mg kg-1 lacidipine which did not lower SBP but
      significantly prevented ventricle hypertrophy and cardiac preproET-1-mRNA
      expression in SL-SHRSP was inactive in control SHRSP. With the higher dose of
      lacidipine (1 mg kg-1 day-1), we observed a further reduction of cardiac
      hypertrophy and of ET-1 gene expression in SL-SHRSP and a significant effect on
      those parameters in control SHRSP but only a small reduction of SBP in both
      groups. 3. In WKY, salt loading did not induce change in SBP or increase of
      cardiac ET-1 gene expression and ventricle mass. In these normotensive rats,
      lacidipine (1 mg kg-1 day-1) did not modulate the basal preproET-1-mRNA
      expression and did not affect SBP or heart weight. 4. The maximum binding
      capacity (Bmax) and the dissociation constant (KD) of [125I]-ET-1 binding and the
      relative proportion of low- and high-affinity binding sites for ET-3 were not
      significantly affected by salt loading or lacidipine treatment in SHRSP. 5. These
      results show that lacidipine exerted a dose-related inhibition of ventricle
      hypertrophy and preproET-1-mRNA expression in SHRSP and indicate that this effect
      was unrelated to SBP changes. The dose-dependency of this inhibition suggests
      that salt-induced cardiac hypertrophy could be related to ET-1 gene
      overexpression. The results further show that ET receptor changes are not
      involved in the pathophysiological process studied here.

PMID- 8762092
TI  - Selective and functional 5-hydroxytryptamine4 receptor antagonism by SB 207266.
AB  - 1. The pharmacology of a novel 5-HT4 receptor antagonist, SB 207266 has been
      evaluated in vitro in the guinea-pig distal colon longitudinal muscle myenteric
      plexus (LMMP) and in vivo in the dog Heidenhain pouch. 2. SB 207266 is a highly
      potent antagonist of 5-HT-evoked, cholinergically-mediated contractions in the
      guinea-pig distal colon. Low concentrations (0.1-10 nM) produced a parallel shift
      to the right of the concentration-effect curve (apparent pA2 10.6 +/- 0.1) with
      no significant effect on the maximum response. With higher concentrations of SB
      207266 (30 nM and above) the maximum response to 5-HT was reduced. 3. The
      antagonism seen with SB 207266 cannot be attributed to a non-selective effect
      since high concentrations (1 microM) had no effect on cholinergically-mediated
      contractions evoked by the nicotinic receptor agonist DMPP in the same
      preparation. 4. SB 207266 is not an irreversible antagonist since the effects of
      the compound were reversible upon washing of the tissue. 5. In the dog Heidenhain
      pouch, oral (0.1-100 micrograms kg-1) and intravenous (0.1-100 micrograms kg-1)
      administration of SB 207266 produced a dose-dependent antagonism of the
      contractions evoked by a bolus intravenous injection of 5-HT. An ID50 for SB
      207266 of 1.3 micrograms kg-1 was obtained following i.v. administration and 9.6
      micrograms kg-1 following oral administration. 6. The antagonistic effects of SB
      207266 (0.1-100 micrograms kg-1) in the dog Heidenhain pouch were long lasting
      since, following oral administration, the response to 5-HT was reduced for at
      least 135 min. 7. SB 207266 is a highly potent, highly selective and orally
      active 5-HT4 receptor antagonist. This compound is the first orally active amide
      to be identified in this class of antagonists and as such is an important new
      tool in the evaluation of 5-HT4 receptor function both in vitro and in vivo.

PMID- 8762093
TI  - Intraplantar morphine depresses spinal c-Fos expression induced by carrageenin
      inflammation but not by noxious heat.
AB  - 1. We have studied the effects of intraplantar administration of the same doses
      of morphine on intraplantar carrageenin (6 mg 150 microliters-1 of saline) and
      noxious heat (52 degrees C for 15 s) induced spinal c-Fos expression and
      inflammation. 2. Intraplantar carrageenin, in awake rats, induced numerous Fos
      like immunoreactive (Fos-LI) neurones in the dorsal horn of L4-L5 lumbar segments
      of the spinal cord and extensive peripheral oedema. At 1 h 30 min, Fos-LI
      neurones were preferentially located in the superficial laminae (74 +/- 2%)
      whereas at 3 h, Fos-LI neurones were observed both in the superficial (45 +/- 2%)
      and deep (37 +/- 1%) laminae of the spinal dorsal horn. 3. Intraplantar morphine
      dose-dependently reduced c-Fos expression induced 1 h 30 min after carrageenin (r
      = 0.605, P < 0.02), these effects were completely blocked by intraplantar
      methiodide naloxone (20 micrograms) (121 +/- 22% of control carrageenin
      expression). The systemic injection of the highest dose of intraplantar morphine
      (50 micrograms) had no significant effect on the number of Fos-LI neurones (88 +/
      9% of control carrageenin expression). None of the drugs influenced unilateral
      peripheral oedema observed 1 h 30 min after carrageenin. 4. In the second series
      of experiments, intraplantar morphine dose-dependently reduced the number of
      superficial and deep Fos-LI neurones induced 3 h after carrageenin (r = 0.794, P
      < 0.0004 and r = 0.698, P < 0.004, respectively). Furthermore, the effects of the
      highest dose of intraplantar morphine were completely blocked by co
      administration of intraplantar methiodide naloxone (20 micrograms). 5. In
      addition, intraplantar morphine dose-dependently reduced the ankle (r = 0.747, P
      < 0.002) and paw (r = 0.682, P < 0.005) oedema observed 3 h after carrageenin,
      with the effect of the highest dose of intraplantar morphine being completely
      blocked by co-administration of methiodide naloxone (98 +/- 4% and 102 +/- 8% of
      control paw and ankle oedema, respectively). 6. Brief noxious heat stimulation,
      in urethane anaesthetized rats, induced, 2 h after the stimulation, numerous Fos
      LI neurones in the dorsal horn of L3-L4 lumbar segments of the spinal cord but no
      detectable peripheral oedema. Fos-LI neurones were preferentially located in
      superficial laminae (94 +/- 2%) of the spinal dorsal horn. None of the drugs
      influenced the noxious heat induced c-Fos expression. 7. Such results illustrate
      that peripheral effects of morphine preferentially occur during inflammatory
      states and outline the interest of extending clinical investigations of the
      possible use of local injection of morphine in various inflammatory pain states.

PMID- 8762094
TI  - Functional characterization of 5-HT1D autoreceptors on the modulation of 5-HT
      release in guinea-pig mesencephalic raphe, hippocampus and frontal cortex.
AB  - 1. The aims of the present study were (i) to characterize further the
      pharmacology of 5-HT1D autoreceptors modulating 5-HT release in guinea-pig
      mesencephalic raphe, hippocampus and frontal cortex; (ii) to determine whether 5
      HT1D receptors in the mesencephalic raphe are located on 5-HT neurones; (iii) to
      determine whether 5-HT1D autoreceptors are coupled to G proteins; and (iv) to
      assess their sensitivity following long-term 5-HT reuptake blockade and
      inhibition of type-A monoamine oxidase. 2. In mesencephalic raphe, hippocampus
      and frontal cortex slices, the 5-HT1D/1B receptor agonist, sumatriptan and the 5
      HT1 receptor agonist, 5-methoxytryptamine (5-MeOT) but not the 5-HT1B receptor
      agonist, CP93129, inhibited electrically the evoked release of [3H]-5-HT in a
      concentration-dependent manner. This effect was antagonized by the 5-HT1D/1B
      receptor antagonist GR127935 in the three structures, but not by the 5-HT1A
      receptor antagonist, (+)-WAY100635 in mesencephalic raphe slices. These results
      confirm the presence of functional 5-HT1D autoreceptors controlling 5-HT release
      within the mesencephalic raphe as well as in terminal regions. 3. The inhibitory
      effect of sumatriptan on K(+)-evoked release of [3H]-5-HT was not reduced by the
      addition of the Na+ channel blocker, tetrodotoxin to the superfusion medium,
      suggesting that these 5-HT1D receptors in the mesencephalic raphe are located on
      5-HT neurones and may be considered autoreceptors. 4. The in vitro treatment with
      the alkylating agent N-ethylmaleimide (NEM) was used to determine whether these 5
      HT1D autoreceptors are coupled to G proteins. The inhibitory effect of
      sumatriptan on electrically evoked release of [3H]-5-HT was attenuated in NEM
      pretreated slices from mesencephalic raphe, hippocampus and frontal cortex,
      indicating that the 5-HT1D autoreceptors activated by sumatriptan are coupled to
      G proteins in these three structures. Taken together with our previous results,
      this suggests that, in addition to the 5-HT1D autoreceptor activated by
      sumatriptan, another subtype of 5-HT autoreceptor is activated by 5-MeOT in the
      hippocampus. 5. Following a 3-week treatment with the selective 5-HT reuptake
      inhibitor, paroxetine (10 mg kg-1 day-1) and a 48 h washout period, the
      electrically evoked release of [3H]-5-HT was enhanced in mesencephalic raphe,
      hippocampus and frontal cortex slices. There was an attenuation of the capacity
      of sumatriptan to inhibit the evoked release of [3H]-5-HT from mesencephalic
      raphe slices but not from frontal cortex and hippocampus slices. Only in the
      latter structure was the suppressant effect of 5-MeOT attenuated. After a 3-week
      treatment with the reversible type-A monoamine oxidase inhibitor, befloxatone
      (0.75 mg kg-1 day-1) and 48 h washout period, the effectiveness of sumatriptan
      and 5-MeOT on the evoked release of [3H]-5-HT was unaltered in the same brain
      structures. 6. The enhancement of [3H]-5-HT release by long-term paroxetine
      treatment is possibly due to a desensitization of 5-HT1D autoreceptors activated
      by sumatriptan in mesencephalic raphe and by terminal 5-HT autoreceptors
      activated by 5-MeOT in hippocampus. In the case of the frontal cortex, it appears
      that 5-MeOT and sumatriptan may act on the same 5-HT1D autoreceptor which is not
      desensitized either after paroxetine or befloxatone treatment, as previously
      reported.

PMID- 8762095
TI  - Effect of calmodulin antagonists on calmodulin-induced biphasic modulation of
      Ca(2+)-induced Ca2+ release.
AB  - 1. Calmodulin (CaM) has a biphasic effect on Ca(2+)-induced Ca2+ release (CICR)
      from the sarcoplasmic reticulum (SR): potentiation and inhibition at low (pCa >
      6.0) and high (pCa 5) Ca2+ concentrations, respectively. To characterize the mode
      of action of CaM, we studied the effect of CaM antagonists on the CICR in skinned
      muscle fibres of the rabbit. Ca2+ release was measured by microfluorometry with
      Fura-2. 2. A CaM antagonist, trifluoperazine (TFP), potentiated the CICR in a
      dose-dependent manner (10-300 microM) at pCa 6, where a simple reversal of the
      CaM effect would be inhibition of the CICR. Furthermore, 100 microM TFP
      sensitized the CICR to Ca2+. A similar effect was produced by other CaM
      antagonists that were tested: chlorpromazine, W-7, mastoparan, and peptide
      fragment of CaM-binding residues of CaM-dependent protein kinase II. 3. The
      biphasic effect of CaM on the CICR was observed even in the presence of high
      concentrations of CaM antagonists or CaM-bindings peptides. 4. From these results
      we suggest that CaM has a unique mode of action on the CICR which is quite
      different from the effect of CaM on known enzymes.

PMID- 8762096
TI  - ATP and nitric oxide: inhibitory NANC neurotransmitters in the longitudinal
      muscle-myenteric plexus preparation of the rat ileum.
AB  - 1. The nature of neurotransmitter(s) involved in non-adrenergic non-cholinergic
      (NANC) relaxations induced by electrical stimulation (10 s trains, 1-8 Hz) was
      investigated in the precontracted longitudinal muscle-myenteric plexus
      preparation of the rat ileum. 2. Electrical stimulation of the tissue induced
      complex responses, consisting of a primary contraction, a primary relaxation, an
      off-relaxation and a rebound contraction, which were all tetrodotoxin(TTX)
      sensitive. 3. Vasoactive intestinal polypeptide (VIP) and carbon monoxide (CO)
      did not induce relaxations. alpha-Chymotrypsin did not reduce the relaxations
      induced by electrical stimulation, while zinc protoporphyrin IX had non-specific
      effects. 4. Nitric oxide (NO) induced concentration-dependent relaxations. NG
      nitro-L-arginine methylester (L-NAME) abolished the primary contractions and off
      relaxations, while it partially reduced the primary relaxations. 5. ATP induced
      relaxations and ATP-desensitization of the tissues partially reduced the primary
      relaxations. Suramin and reactive blue 2 did not consistently influence the
      primary relaxations. 6. The ATP-induced relaxations were not influenced by L-NAME
      or TTX. The inhibitory effect of ATP-desensitization and L-NAME did not summate.
      7. The cyclic AMP content of the tissue did not increase upon electrical
      stimulation or after addition of NO or ATP. The cyclic GMP content of the tissue
      increased upon electrical stimulation and addition of NO, but not after addition
      of ATP. 8. It is concluded that the relaxation induced by electrical stimulation
      consists of two types of responses. The off-relaxation is completely nitrergic,
      while the primary relaxation is mediated by NO, ATP and an as yet unknown
      transmitter which is not VIP or CO.

PMID- 8762097
TI  - PPADS and suramin as antagonists at cloned P2Y- and P2U-purinoceptors.
AB  - 1. The effect of suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic
      acid (PPADS) on the stimulation of phospholipase C in 1321N1 cells transfected
      with the human P2U-purinoceptor (h-P2U-1321N1 cells) or with the turkey P2Y
      purinoceptor (t-P2Y-1321N1 cells) was investigated. 2-Methylthioadenosine
      triphosphate (2MeSATP) was used as the agonist at t-P2Y-1321N1 cells and uridine
      triphosphate (UTP) at h-P2U-1321N1 cells. 2. Suramin caused a parallel shift to
      the right of the concentration-response curves for 2MeSATP in the t-P2Y-1321N1
      cells, yielding a Schild plot with a slope of 1.16 +/- 0.08 and a pA2 value of
      5.77 +/- 0.11. 3. Suramin also caused a shift to the right of concentration
      response curves for UTP in the h-P2U-1321N1 cells, and on Schild plots gave a
      slope different from unity (1.57 +/- 0.19) and an apparent pA2 value of 4.32 +/-
      0.13. Suramin was therefore a less potent antagonist at the P2U-purinoceptor than
      the P2Y-purinoceptor. 4. In the presence of the ectonucleotidase inhibitor, ARL
      67156 (6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP) there was no significant
      difference in the EC50 or shapes of curves with either cell type, and no
      difference in pA2 values for suramin. 5. PPADS caused an increase in the EC50 for
      2MeSATP in the t-P2Y-1321N1 cells. The Schild plot had a slope different from
      unity (0.55 +/- 0.15) and an X-intercept corresponding to an apparent pA2 of 5.98
      +/- 0.65. 6. PPADS up to 30 microM had no effect on the concentration-response
      curve for UTP with the h-P2U-1321N1 cells. 7. In conclusion, suramin and PPADS
      show clear differences in their action at the 2 receptor types, in each case
      being substantially more effective as an antagonist at the P2Y-purinoceptor than
      at the P2U-purinoceptor. Ectonucleotidase breakdown had little influence on the
      nature of the responses at the two receptor types, or in their differential
      sensitivity to suramin.

PMID- 8762098
TI  - Further investigations into the mechanism of the antihypertensive activity of the
      angiotensin AT1 receptor antagonist, GR138950.
AB  - 1. The angiotensin AT1 receptor antagonist, GR138950, produces a long-lasting
      antihypertensive effect in conscious renal artery ligated hypertensive (RALH)
      rats but this effect does not correlate temporally with its antagonist profile
      against angiotensin II (AII). In the present experiments we have compared the
      inhibitory profiles of GR138950 and enalapril, against angiotensin I (AI), with
      their respective antihypertensive activities. 2. GR138950 (1 mg kg-1, i.a.) and
      enalapril (3 mg kg-1, i.a.) reduced blood pressure in RALH rats to a similar
      degree. Maximum reductions in blood pressure occurred approximately 5-24 h and 3
      5 h after administration, respectively. The antihypertensive effect of GR138950
      lasted for 24-48 h. However, the effect of enalapril lasted for only 5-24 h. 3.
      In conscious normotensive rats, inhibition of AI-induced pressor responses was
      maximal 1 h after systemic administration of GR138950 and enalapril. Dose
      response curves to AI were displaced to the right, in a parallel manner, 1406 and
      102 fold by GR138950 (1 mg kg-1, i.a.) and enalapril (3 mg kg-1 i.a.),
      respectively. The inhibitory effect of enalapril lasted for < 24 h whereas that
      of GR138950 lasted for up to 48 h. 4. Contractile responses to AI were
      extensively inhibited in aortae removed from either RALH rats or normotensive
      rats, 1 and 5 h after administration of GR138950 (1 mg kg-1, i.a.). Responses
      were still significantly reduced 24 h after administration but had returned to
      control levels after 48 h. Enalapril pretreatment (3 mg kg-1, i.a.) did not
      inhibit contractile responses to AI in aortae isolated from normotensive rats at
      any time point. 5. These experiments confirm that GR138950 is an effective and
      long-lasting antihypertensive agent. GR138950 was a more potent and longer
      lasting antagonist against AI than has previously been found against AII, and the
      duration of its antihypertensive activity coincides better with its blockade of
      responses to AI. Blockade of the effects of AII generated locally within the
      vascular wall might play an important role in the antihypertensive profile of
      GR138950.

PMID- 8762099
TI  - Mechanotransduction through the endothelial cytoskeleton: mediation of flow- but
      not agonist-induced EDRF release.
AB  - 1. We have used a cascade bioassay system and isolated arterial ring preparations
      to investigate the contribution of the endothelial microfilament and microtubule
      cytoskeleton to EDRF release evoked by time-averaged shear stress and by
      acetylcholine in rabbit abdominal aorta. 2. Cytochalasin B (1 microM) and
      phalloidin (100 nM) were used to depolymerize and stabilize, respectively, F
      actin microfilaments. Colchicine (500 nM) was used to inhibit tubulin
      dimerization and thus disrupt the microtubule network. Experiments were performed
      before or 1 h after administration of agents to the donor perfusate or organ
      bath. 3. In cascade bioassay studies, time-averaged shear stress was manipulated
      with dextran (1-4% w/v, 80,000 MW), to increase perfusate viscosity. EDRF release
      induced by increased perfusate viscosity was significantly (P < 0.01) attenuated
      by cytochalasin B, phalloidin and colchicine. 4. Endothelium-dependent
      relaxations to acetylcholine (0.01-30 microM) in cascade bioassay and in isolated
      aortic ring preparations were unaffected by pretreatment with any of these agents
      both in terms of their EC50 and maximal responses. Endothelium-independent
      relaxations to sodium nitroprusside (0.001-10 microM) were similarly unaffected.
      5. We conclude that the endothelial F-actin microfilament and microtubule
      networks are involved in the mechanotransduction pathway for flow-evoked EDRF
      release in rabbit abdominal aorta. However, these cytoskeletal elements appear to
      play no role in acetylcholine-induced EDRF release in this tissue.

PMID- 8762100
TI  - Antithrombotic actions of the thrombin inhibitor, argatroban, in a canine model
      of coronary cyclic flow: comparison with heparin.
AB  - 1. The antithrombotic action of argatroban, a synthetic thrombin inhibitor, was
      studied in a canine model of coronary cyclic flow having some of the
      characteristics of acute unstable angina. Heparin was studied as a reference
      anticoagulant. 2. Localized endothelial damage was induced in the circumflex
      coronary artery of anaesthetized open-chest foxhounds and a critical stenosis was
      applied by use of a Lexan constrictor placed around the artery at the site of
      endothelial damage. An electro-magnetic flow probe was placed distal to the
      lesion, and cyclic flow variations (CFVs) were observed, as thrombi formed at the
      site of the arterial lesion and were dislodged. Test compounds were administered
      by i.v. infusion commencing 1 h after the appearance of CFVs, and maintained for
      1 h. On termination of the treatments, coronary flow was observed for a further
      60 min. A series of blood samples were taken at predetermined times throughout
      each experiment in order to determine the coagulation parameters, thrombin time
      (TT) activated partial thromboplastin time (aPTT) and for the determination of
      fibrinopeptide A (FpA) levels before, during and post-treatment. 3. Argatroban
      and heparin showed antithrombotic effects in this model. Argatroban dose
      dependently increased the minimum coronary flow at the nadir of the CFVs from 5.4
      +/- 1.7 to 9.1 +/- 2.1 ml min-1 (30 micrograms kg-1 min-1, P = 0.041) and from
      2.9 +/- 0.9 to 16.3 +/- 4.5 ml min-1 (100 micrograms kg-1 min-1, P = 0.023, n = 8
      dogs at each dose level). Heparin (5 and 15 iu kg-1 min-1) also increased minimum
      flow, but the increase was not statistically significant at the 5% level,
      although the P value in animals treated with 15 iu kg-1 min-1 (P = 0.0521, n = 6
      dogs) fell just outside this limit. Although neither compound significantly
      decreased the overall CFV frequency, argatroban (100 micrograms kg-1 min-1)
      significantly (P < 0.01) decreased the number of large amplitude CFVs (minimum
      coronary flow < 10 ml min-1) by 63%, and heparin (15 iu kg-1 min-1) caused a 50%
      decrease in this parameter (P < 0.05). 4. The thrombin times were increased by a
      factor greater than 10 during antithrombotic treatment, irrespective of the
      compound or doses used. Heparin treatment induced 17 and > 30 fold increases in
      aPTT at 5 and 15 iu kg-1 min-1 respectively. However, argatroban produced only 2
      and 3 fold increases in aPTT at 30 and 100 micrograms kg-1 min-1, despite
      significant antithrombotic effects. FpA levels were reduced in the presence of
      both argatroban and heparin. 5. These data show that, when administered as an
      intravenous infusion, argatroban is a potent antithrombotic agent in a canine
      model of coronary cyclic flow.

PMID- 8762101
TI  - Characterization of the anatomical structures involved in the contractile
      response of the rat lung periphery.
AB  - 1. When lung parenchymal strips are challenged with different smooth muscle
      agonists, the tensile and viscoelastic properties change. It is not clear,
      however, which of the different anatomical elements present in the parenchymal
      strip, i.e., small vessel, small airway or alveolar wall, contribute to the
      response. 2. Parenchymal lung strips from Sprague Dawley rats were suspended in
      an organ bath filled with Krebs solution (37 degrees C, pH = 7.4) bubbled with
      95%O2/5%CO2. Resting tension (T) was set at 1.1 g and sinusoidal oscillations of
      2.5% resting length (L0) at a frequency of 1 Hz were applied. Following 1 h of
      stress adaptation, measurements of length (L) and T were recorded under baseline
      conditions and after challenge with a variety of pharmacological agents, i.e.,
      acetylcholine (ACh), noradrenaline (NA) and angiotensin II (AII). Elastance (E)
      and resistance (R) were calculated by fitting changes in T, L and delta L/ delta
      t to the equation of motion. Hysteresivity (eta, the ratio of the energy
      dissipated to that conserved) was obtained from the equation eta = (R/E)2 pi f.
      3. In order to determine whether small airways or small vessels accounted for the
      responses to the different pharmacologic agents, further studies were carried out
      in lung explants. Excised lungs from Sprague Dawley rats were inflated with
      agarose. Transverse slices of lung (0.5-1.0 mm thick) were cultured overnight. By
      use of an inverted microscope and video camera, airway and vascular lumen area
      were measured with an image analysis system. 4. NA, ACh and AII constricted the
      parenchymal strips. Airways constricted after all agonists, vessels constricted
      only after All. Atropine (Atr) pre-incubation decreased the explanted airway and
      vessel response to AII, but no difference was found in the parenchymal strip
      response. 5. Preincubation with the arginine analogue N omega-nitro-L-arginine (L
      NOARG) did not modify the response to ACh but mildly increased the oscillatory
      response to NA after co-preincubation with propranolol (Prop). 6. These results
      suggest that during ACh and NA challenge, small vessels do not contribute
      substantially to the parenchymal strip response. The discrepancy between results
      in airways, vessels and strips when Atr was administered prior to AII implicates
      a direct contractile response in the parenchymal strip.

PMID- 8762102
TI  - Studies on the pharmacology of the inward transport of L-DOPA in rat renal
      tubules.
AB  - 1. The accumulation of L-DOPA in suspensions of renal tubules obtained from male
      Wistar rats occurred through non-saturable and saturable mechanisms. The kinetics
      of the saturable component of L-DOPA uptake in renal tubules was as follows: Vmax
      = 46.3 +/- 2.8 nmol mg-1 protein h-1 and Km = 114.4 (95% confidence limits; 83.8,
      156.2) microM (n = 5). The diffusion constant (in nmol-1) of the non-saturable
      component for the accumulation of L-DOPA was 1.3 (1.1, 1.6; n = 8). 2. The effect
      of 2,4-dinitrophenol was a marked reduction in the tubular uptake of L-DOPA, with
      an IC50 value of 12.1 (4.0, 36.9) microM. Cocaine produced a slight (P = 0.08)
      decrease (22% reduction at 50 microM) in the tubular uptake of L-DOPA.
      Corticosterone produced a considerable inhibitory effect on the uptake of L-DOPA
      with an IC50 value of 11.0 (3.6, 33.5) microM. The maximal inhibitory effect of
      probenecid was a 24% decrease in the uptake of L-DOPA; however, the more
      selective organic anion transport inhibitor 4,4'-diisothiocyantostilbene-2,2'
      disulphonic acid (DIDS) was, found not to affect the tubular uptake of L-DOPA.
      The organic cation transport inhibitor, cyanine 863, was found to produce a
      marked decrease in the uptake of L-DOPA (IC50 = 2.02 [1.07, 3.79]). The cyanine
      derivatives 1,1'-diethyl-2,2'-cyanine (decynium 22) and 1,1'-diethyl-2,4'-cyanine
      (decynium 24) also potently inhibited L-DOPA uptake with IC50 values (in microM)
      of 0.63 (0.39, 1.01) and 0.10 (0.08, 0.13), respectively, both compounds were
      found to be more potent than cyanine 863. 3. The inhibitory effect of decynium 24
      (0.2 microM) on the tubular uptake of L-DOPA was dependent on the pH of the
      incubation medium; at pH = 6.5 the accumulation of L-DOPA was reduced up to 37 +/
      2% of control values, whereas at pH = 7.4 and pH = 8.2 the accumulation of L
      DOPA was reduced by 56 +/- 1% and 60 +/- 6%, respectively. Cyanine 863 (2
      microM), decynium 22 (1 microM) and decynium 24 (0.2 microM) were found to
      decrease the Vmax values for the saturable component of L-DOPA uptake without
      changes in Km values. 4. It is concluded that the tubular uptake of L-DOPA might
      be promoted through a mechanism which is dependent on the activity of the organic
      cation transport system.

PMID- 8762103
TI  - Endogenous calcium channels in human embryonic kidney (HEK293) cells.
AB  - 1. We have identified endogenous calcium channel currents in HEK293 cells. Whole
      cell endogenous currents (ISr-HEK) were studied in single HEK293 cells with 10 mM
      strontium as the charge carrier by the patch clamp technique. The kinetic
      properties and pharmacological features of ISr-HEK were characterized and
      compared with the properties of a heterologously expressed chimeric L-type
      calcium channel construct. 2. ISr-HEK activated on depolarization to voltages
      positive of -40 mV. It had transient current kinetics with a time to peak of 16
      +/- 1.4 ms (n = 7) and an inactivation times constant of 52 +/- 5 ms (n = 7) at a
      test potential of 0 mV. The voltage for half maximal activation was -19.0 +/- 1.5
      mV (n = 7) and the voltage for half maximal steady-state inactivation was -39.7
      +/- 2.3 mV (n = 7). 3. Block of ISr-HEK by the dihydropyridine isradipine was not
      stereoselective; 1 microM (+) and (-)-isradipine inhibited the current by 30 +/-
      4% (n = 3) and 29 +/- 2% (n = 4) respectively. (+)-Isradipine and (-)-isradipine
      (10 microM) inhibited ISr-HEK by 89 +/- 4% (n = 5) and 88 +/- 8% (n = 3)
      respectively. The 7-bromo substituted (+/-)-isradipine (VO2605, 10 microM) which
      is almost inactive on L-type calcium channels also inhibited ISr-HEK (83 +/- 9%,
      n = 3) as was observed for 10 microM (-)-nimodipine (78 +/- 6%, n = 5).
      Interestingly, 10 microM (+/-)-Bay K 8644 (n = 5) had no effect on the current.
      ISr-HEK was only slightly inhibited by the cone snail toxins omega-CTx GVIA (1
      microM, inhibition by 17 +/- 3%, n = 4) and omega-CTx MVIIC (1 microM, inhibition
      by 20 +/- 3%, n = 4). The funnel web spider toxin omega-Aga IVA (200 nM)
      inhibited ISr-HEK by 19 +/- 2%, n = 4). 4. In cells expressing ISr-HEK, maximum
      inward current densities of 0.24 +/- 0.03 pA/pF and 0.39 +/- 0.7 pA/ pF (at a
      test potential of -10 mV) were estimated in two different batches of HEK293
      cells. The current density increased to 0.88 +/- 0.18 pA/pF or 1.11 +/- 0.2 pA/pF
      respectively, if the cells were cultured for 4 days in serum-free medium. 5. Co
      expression of a chimeric L-type calcium channel construct revealed that ISr-HEK
      and L-type calcium channel currents could be distinguished by their different
      voltage-dependencies and current kinetics. The current density after heterologous
      expression of the L-type alpha 1 subunit chimera was estimated to be about ten
      times higher in serum containing medium (2.14 +/- 0.45 pA/pF) than that of ISr
      HEK under the same conditions.

PMID- 8762104
TI  - Presynaptic modulation by L-glutamate and GABA of sympathetic co-transmission in
      rat isolated vas deferens.
AB  - 1. The modulatory effects of L-glutamate and its structural analogues, and of
      gamma-aminobutyric acid (GABA), on sympathetic co-transmission were studied in
      the rat isolated vas deferens exposed to electrical field stimulation (EFS). 2.
      Application of exogenous L-glutamate caused a concentration-dependent (1 microM-3
      mM) inhibition of the rapid twitch component of the biphasic EFS contraction.
      However, L-glutamate (1 microM-3 mM) had a minimal effect on the phasic
      contraction induced by exogenous adenosine 5'-triphosphate (ATP, 150 microM) and
      noradrenaline (50 microM). Unlike L-glutamate, D-glutamate had no effect on the
      EFS contraction. 3. The L-glutamate-induced inhibition of the EFS contractions
      was significantly attenuated by the glutamate decarboxylase (GAD) inhibitor 3
      mercapto-propionic acid (150 microM) and was abolished in the presence of the
      GABA transaminase (GABA-T) inhibitor, 2-aminoethyl hydrogen sulphate (500
      microM). 4. The L-glutamate-induced inhibition of the electrically evoked
      contraction was not affected by the adenosine A1-receptor antagonist, 8
      cyclopentyl-1,3-dipropylxanthine (DPCPX)(30 nM), reactive blue 2 (30 microM) or
      the GABAA receptor antagonist bicuculline (50 microM). However, the GABAB
      receptor antagonist 2-hydroxysaclofen (50 microM) significantly inhibited the L
      glutamate effect. 5. Similar to L-glutamate, GABA also caused a concentration
      dependent (0.1-100 microM) inhibition of the EFS contractions. This GABA-induced
      inhibition was not affected by either the GABAA receptor antagonist bicuculline
      (50 microM) or reactive blue 2 (30 microM). However, a significant attenuation of
      the GABA-mediated effect was recorded with the GABAB receptor antagonist 2
      hydroxysaclofen (50 microM). Contractions of the vas deferens induced by
      exogenous ATP and noradrenaline were not affected by GABA (0.1-100 microM). 6.
      The L-glutamate analogues, N-methyl-D-aspartate (NMDA) (1 microM-1 mM) and
      quisqualate (Quis 0.1 microM-0.3 mM) had no effect, whilst kainate (Kain, 1
      microM-1 mM) caused an inhibition of the EFS-induced contractions. Effects of
      Kain could be abolished by the non-NMDA receptor antagonist 6-cyano-7
      nitroquinoxaline-2,3-dioxine (CNQX, 10 microM). NMDA, Quis and Kain had no effect
      on the exogenous ATP- or noradrenaline-induced contractions. 7. It is concluded
      that the excitatory amino acid L-glutamate modulates the electrically evoked vas
      deferens contraction through conversion to the inhibitory amino acid GABA by a
      specific GABA transaminase. The GABA formed may then act on GABAB receptors and
      cause inhibition of the contraction through a presynaptic mechanism.

PMID- 8762105
TI  - Inhibition by endothelin-1 of cholinergic nerve-mediated acetylcholine release
      and contraction in sheep isolated trachea.
AB  - 1. The relative roles of ETA and ETB receptor activation on cholinergic nerve
      mediated contraction and acetylcholine (ACh) release were examined in sheep
      isolated tracheal smooth muscle. 2. Electrical field stimulation (EFS; 90 V, 0.5
      ms duration, 1 Hz, 10 s train) applied to sheep isolated tracheal smooth muscle
      strips induced monophasic contractile responses that were abolished by either 1
      microM tetrodotoxin or 0.1 microM atropine, but were insensitive to 10 microM
      hexamethonium and 100 microM L-NAME. Thus, EFS-induced contractions resulted from
      the spasmogenic actions of ACh released from parasympathetic, postganglionic
      nerves. 3. As expected, sheep isolated tracheal smooth muscle preparations did
      not contract in response to the ETB receptor-selective agonist, sarafotoxin S6c
      (0.1-100 nM). However, sarafotoxin S6c caused a concentration-dependent and
      transient inhibition of EFS-induced contractions. The inhibitory effect induced
      by a maximally effective concentration of sarafotoxin S6c (10 nM; 72.1 +/- 5.7%,
      n = 6) was abolished in the presence of the ETB receptor-selective antagonist BQ
      788 (1 microM). Contractile responses to exogenously administered ACh (10 nM-0.3
      mM) were not inhibited by sarafotoxin S6c (1 or 10 nM; n = 7). 4. In contrast to
      sarafotoxin S6c, endothelin-1 induced marked contractions in sheep isolated
      tracheal smooth muscle. These contractions were inhibited by BQ-123, consistent
      with an ETA receptor-mediated response. In the presence of BQ-123 (3 microM),
      endothelin-1 produced a concentration-dependent inhibition of EFS-induced
      contractions (30 nM endothelin-1, 68.9 +/- 10.2% inhibition, n = 5). These
      responses were inhibited by 1 microM BQ-788, indicative of an ETB receptor
      mediated process. Endothelin-1 was about 3 fold less potent than sarafotoxin S6c.
      5. EFS (90 V, 0.5 ms duration, 1 Hz, 15 min train) induced the release of
      endogenous ACh (1.94 +/- 0.28 pmol mg-1 tissue, n = 12), as assayed by h.p.l.c.
      with electrochemical detection. EFS-induced release of ACh was inhibited to a
      similar extent by 100 nM endothelin-1 (47 +/- 4%, n = 9) and 10 nM sarafotoxin
      S6c (46 +/- 9%, n = 3). These effects of endothelin-1 on ACh release were
      inhibited by 1 microM BQ-788 alone (n = 4), by BQ-788 in the presence of 3 microM
      BQ-123 (n = 4), but not by 3 microM BQ-123 alone (n = 5). 6. In summary, sheep
      isolated tracheal smooth muscle contains two anatomically and functionally
      distinct endothelin receptor populations. ETA receptors located on airway smooth
      muscle mediate contraction, whereas ETB receptors appear to exist on cholinergic
      nerves that innervate tracheal smooth muscle cells and mediate inhibition of ACh
      release. The inhibitory effect of ETB receptor stimulation on cholinergic
      neurotransmission is in stark contrast to the enhancing effects hitherto
      described in the airways.

PMID- 8762107
TI  - Inhibition of purinergic transmission by prostaglandin E1 and E2 in the guinea
      pig vas deferens: an electrophysiological study.
AB  - 1. The effects of prostaglandin E1 (PGE1) and E2 (PGE2) on postjunctional
      electrical activity in the guinea-pig vas deferens evoked by sympathetic nerve
      stimulation were investigated using both intracellular and focal extracellular
      recording techniques in vitro. 2. Bath application of PGE1 (1-100 nM) or PGE2
      (0.1-100 nM) concentration-dependently inhibited the amplitudes of all excitatory
      junction potentials (e.j.ps) evoked during short trains of stimuli (10 stimuli at
      1 Hz). Increasing the duration of nerve stimulation (100 stimuli at 1 Hz) did not
      overcome this inhibitory effect. At these concentrations PGE1 and PGE2 were
      without any apparent inhibitory effect on the amplitudes of spontaneous e.j.ps.
      3. Local application of PGE1 (10-100 nM) or PGE2 (10-30 nM) markedly reduced the
      frequency of occurrence of excitatory junction currents (e.j.cs) evoked by trains
      of 20-100 stimuli at 1 to 4 Hz without changing the amplitudes of spontaneous
      e.j.cs or the configuration of the nerve terminal impulse. 4. In the presence of
      PGE1 or PGE2, raising the frequency of stimulation (from 1 to 4 Hz), increased
      the likelihood of e.j.c. occurrence. 5. The postjunctional electrical activity
      recorded in the guinea-pig vas deferens is believed to be due to ATP released
      from the sympathetic nerve endings. Thus the present study demonstrates that both
      PGE1 and PGE2 powerfully inhibit quantal ATP release in the guinea-pig vas
      deferens.

PMID- 8762106
TI  - Desensitization of glucagon-like peptide 1 receptors in insulin-secreting beta
      TC3 cells: role of PKA-independent mechanisms.
AB  - 1. The cellular processes involved in the desensitization of the glucagon-like
      peptide 1 receptors were investigated by measurements of the glucagon-like
      peptide 1(7-36)amide (GLP-1(7-36)amide)-induced increases in intracellular free
      Ca2+ concentration ([Ca2+]i) in insulin-secreting beta TC3 cells. 2. In the
      presence of 11.2 mM glucose, stimulation with GLP-1(7-36)amide led to a small
      membrane depolarization (< 10 mV), induction of electrical activity and a rapid
      increase in [Ca2+]i. The increase in [Ca2+]i was not observed in the presence of
      the L-type Ca(2+)-channel antagonist nifedipine. However, nifedipine was
      ineffective when applied after addition of GLP-1(7-36)amide. 3. The increase in
      [Ca2+]i evoked by GLP-1-(7-36)amide was transient and even in the continued
      presence of the agonist, [Ca2+]i returned to the basal value within 4-5 min. The
      latter process was slowed, but not prevented, by inhibition of protein kinase C
      (PKC) by staurosporine and Ro31-8220. 4. Short pretreatment of the cells with the
      phorbol ester, 4-beta-phorbol-12-beta-myristate-13-alpha-acetate (PMA), an
      activator of PKC, reduced the GLP-1(7-36)amide-evoked increase in [Ca2+]i by 75%.
      This effect of PMA was fully reversed by staurosporine and Ro31-8220. 5. The
      ability of GLP-1(7-36)amide to increase [Ca2+]i disappeared upon pre-exposure of
      the cells to the hormone (desensitization). This process was maximal within 5 min
      of exposure to the agonist. Following removal of the agonist from the medium, the
      ability to respond to subsequent stimulation by GLP-1(7-36)amide recovered
      gradually with time; half and complete recovery requiring > 20 min and 60 min,
      respectively. The desensitizing action of GLP-1(7-36)amide persisted in the
      presence of either staurosporine or forskolin and did not require an elevation of
      [Ca2+]i. 6. Our data suggest that the GLP-1(7-36)amide-evoked increase in [Ca2+]i
      is initiated by Ca(2+)-influx though voltage-dependent and nifedipine-sensitive L
      type Ca2+ channels but depends principally on Ca2+ mobilization from internal
      stores for its maintenance. The desensitization of the GLP-1 receptors that
      occurs in the continued presence of the agonist does not result from the
      activation of protein kinase A or Ca(2+)-dependent kinases/phosphatases. Our data
      indicate that activation of PKC may contribute to the desensitization of the GLP
      1 receptors but that other (PKC-independent) mechanisms also participate in this
      process.

PMID- 8762108
TI  - Adenosine inhibitory effect on enhanced growth of aortic smooth muscle cells from
      streptozotocin-induced diabetic rats.
AB  - 1. There is evidence to suggest that adenosine may regulate arterial smooth
      muscle cell (SMC) growth and proliferation, which is a key event in
      atherogenesis. This regulation may be mediated via adenylate cyclase. As diabetes
      is a known risk factor for atherosclerosis, we investigated the growth of aortic
      SMC from diabetic rats in primary culture and their sensitivity to adenosine and
      to adenylate cyclase activity. 2. Diabetes was induced with streptozotocin (STZ,
      66 mg kg-1, i.p.) Aortic SMC primary cultures were prepared from STZ-diabetic and
      age-matched rats 5 weeks after the STZ injection. 3. SMC from STZ-diabetic rats
      grew faster and reached greater densities at confluence than those from non
      diabetic animals. 4. Adenosine inhibited growth in both control and diabetic SMC.
      However, cells from STZ-diabetic rats were apparently more sensitive to
      adenosine. 5. Direct activation of adenylate cyclase by forskolin induced a dose
      dependent growth inhibition, similar in both groups of cells. 6. Cholera toxin,
      an activator of stimulatory GTP-binding protein (Gs), induced a similar growth
      inhibitory response in non-diabetic and diabetic SMC. Pertussis toxin (PTX), an
      inactivator of inhibitory GTP-binding protein (Gi), did not itself affect SMC
      growth. However, PTX increased dose-dependently the growth inhibition induced by
      adenosine in SMC from non-diabetic rats but not in SMC from diabetic rats. 7.
      These findings suggest a functional abnormality in Gi activity in SMC from
      diabetic rats, that would explain the increased sensitivity to the nucleoside.
      This impaired inhibitory pathway may reflect changes in the growth regulation of
      SMC in experimental diabetic states.

PMID- 8762109
TI  - Effects of selective phosphodiesterase 3 inhibition in the perfused liver of the
      rat after endotoxin treatment.
AB  - 1. This study was designed to investigate the role of rat phosphodiesterase 3
      (RPDE3) in regulation of liver metabolism in sepsis. We studied the effects of
      the phosphodiesterase 3 inhibitor (PDI), enoximone, alone and in combination with
      regulating factors of hepatic carbohydrate metabolism and bile secretion in the
      perfused liver of rats treated 4 h earlier with endotoxin. In addition, cyclic
      AMP and cyclic GMP levels were determined in the effluate and bile by radio
      immunoassay methods. 2. After endotoxin treatment, infusion of enoximone at three
      concentrations (1 microM, 10 microM) resulted in an increased glucose output from
      -1.4 +/- 0.9 to 7.8 +/- 2.5 mumol l-1 20 min-1. Bile acid-independent bile flow
      increased also, in a dose-dependent manner. 3. In untreated livers, cyclic AMP
      release increased in the effluate from 1000 +/- 73 fmol g-1 min-1 to 1710 +/- 143
      fmol g-1 min-1 when enoximone (10 microM) was administered. In bile from
      untreated livers, the level of cyclic AMP was also significantly increased by
      enoximone. After endotoxin treatment, the enoximone (10 microM) effect on cyclic
      AMP levels in effluate and bile was greatly reduced. Levels of cyclic GMP in the
      effluate and bile appeared unchanged in the presence of enoximone. 4. During co
      infusion of glucagon (1 nM) and enoximone (10 microM), cyclic nucleotide levels
      in the effluate and bile of livers after endotoxin treatment were determined. In
      the effluate, cyclic AMP release increased from 827 +/- 144 fmol g-1 min-1 to
      17802 +/- 2821 fmol g-1 min-1 when glucagon was administered. The presence of
      enoximone enhanced cyclic AMP further to 41696 +/- 920 fmol g-1 min-1. The same
      changes in cyclic AMP release were found in bile. Levels of cyclic GMP in the
      effluate and bile were not significantly affected by the administration of
      glucagon and the PDI. 5. Glucose release was determined during glucagon,
      sympathetic nerves stimulation and phenylephrine administration in the presence
      and absence of enoximone. The addition of enoximone to glucagon increased glucose
      release by 8.2 +/- 2.8 mumol g-1 20 min-1, without alteration of lactate balance.
      The PDI enhanced the glycogenolytic effects of nerve stimulation and of
      phenylephrine, accompanied by a reduction in lactate production. 6. Enoximone
      significantly enhanced the bile acid independent bile flow after glucagon, nerves
      stimulation and after administration of phenylephrine. Bile acid secretion was
      unaffected by the PDI. The vasoconstrictor effect of nerve stimulation was
      reduced by the PDI. 7. We conclude that endotoxin treatment reduces the ability
      of the PDI, enoximone, to increase cyclic AMP release in the perfused liver. The
      significant increase in cyclic AMP release after stimulation with glucagon and
      enoximone favours the view that RPDE3 is involved in the degradation of cyclic
      AMP in the liver after exposure to endotoxin. Additionally, the inhibition of the
      RPDE3 results in glucose release, vasodilatation and choleresis in endotoxin
      pretreated livers.

PMID- 8762110
TI  - Inhibition of neuromuscular transmission in the myenteric plexus of guinea-pig
      ileum by omega-conotoxins GVIA, MVIIA, MVIIC and SVIB.
AB  - 1. The effects of a number of Ca2+ channel blockers on the transmural electrical
      stimulation or receptor agonist-elicited contractile responses of guinea-pig
      ileum were compared. 2. omega-Conotoxins (MVIIA, GVIA, SVIB and MVIIC), but not
      omega-agatoxin IVA, completely blocked the twitch responses evoked by low
      frequency (0.1 Hz) transmural stimulation without inhibition of the contractures
      evoked by exogenous acetylcholine. The concentration-inhibition curves were
      shifted by changes of external Ca2+. 3. The tetanic contractures produced by a
      high frequency (30 Hz) train of stimulation were inhibited by omega-conotoxins by
      only 25-30%, except for omega-conotoxin MVIIC, which produced about 55%
      inhibition, all significantly less than that produced by atropine (about 70%) or
      tetrodotoxin (about 85%). Combinations of omega-conotoxins did not produce
      additive inhibitory effects. 4. The four omega-conotoxins as well as atropine
      produced similar partial inhibition (53-62%) of the contractures evoked by
      dimethylphenylpiperazinium, while tetrodotoxin inhibited the contracture
      completely. 5. Nifedipine and Ni2+ depressed the nerve stimulation-evoked twitch
      response and tetanic contracture as well as acetylcholine contracture. 6. These
      observations suggest that, in the myenteric plexus, a subset of N-type Ca2+
      channel dominates under low frequency stimulation, while high frequency
      stimulation may recruit additional channels and non-cholinergic pathways.

PMID- 8762111
TI  - Study of the mechanisms involved in adenosine-5'-O-(2-thiodiphosphate) induced
      relaxation of rat thoracic aorta and pancreatic vascular bed.
AB  - 1. The endothelium-dependent relaxation of blood vessels induced by P2Y
      purinoceptor activation has often been shown to involve prostacyclin and/or
      nitric oxide (NO) release. In this work, we have investigated the mechanisms
      involved in the relaxant effect of the P2Y agonist, adenosine -5'-O-(2
      thiodiphosphate) (ADP beta S) using two complementary preparations: rat
      pancreatic vascular bed and aortic ring. 2. On the pancreatic vascular bed, ADP
      beta S (1.5 and 15 microM) infused for 30 min induced a concentration-dependent
      vasodilatation; it was progressive during the first 10 min (first period) and
      sustained from 10 to 30 min (second period). Indomethacin (10 microM) delayed ADP
      beta S-induced vasodilatation (1.5 and 15 microM) by about 6 min. N omega-nitro-L
      arginine methyl ester (L-NAME) (200 microM) suppressed the relaxation for about 5
      min but thereafter ADP beta S at the two concentrations progressively induced an
      increase in the flow rate. Even the co-administration of L-NAME and indomethacin
      did not abolish the ADP beta S-induced vasorelaxation. 3. On 5-hydroxy tryptamine
      (5-HT) precontracted rings mounted in isometric conditions in organ baths, we
      observed that ADP beta S induced a concentration-dependent relaxation of rings
      with a functional endothelium; this effect was stable for 25 min. The ADP beta S
      relaxant effect was strongly inhibited by Reactive Blue 2 (30 microM) and was
      suppressed by pretreatment of rings with saponin (0.05 mg ml-1 for 30 min), which
      also abolished the acetylcholine-induced relaxation. 4. ADP beta S-induced
      relaxation of 5-HT precontracted rings is largely inhibited by indomethacin (100
      or 10 microM) or L-NAME (100 microM). 5. We conclude that: the ADP beta S-induced
      relaxation is endothelium-dependent, mediated by P2Y-purinoceptors, and at least
      in part linked to NO and prostacyclin release, depending on the preparation used.
      Furthermore, on the pancreatic vascular bed, (an)other mechanism(s) than
      prostacyclin and NO releases may be involved in ADP beta S-induced
      vasodilatation.

PMID- 8762112
TI  - Anti-inflammatory effects of theophylline, cromolyn and salbutamol in a murine
      model of pleurisy.
AB  - 1. The aim of this study was to examine the effect of theophylline, cromolyn and
      salbutamol, three well-known anti-asthmatic drugs, on the early (4 h) and late
      (48 h) phases of cell migration and fluid leakage induced by carrageenin in the
      pleural cavity of mice. 2. In the first set of experiments, animals were
      pretreated (30 min) with different doses of theophylline (0.5-50 mg kg-1, i.p.),
      cromolyn (0.02-0.2 mg per pleural cavity) or salbutamol (0.05-50 mg kg-1, i.p.);
      the total and differential cell content, and also the exudate were analysed 4 h
      after carrageenin (1%) administration. Afterwards, in order to evaluate the time
      course effects of these drugs on both phases of the inflammatory reaction, one
      dose employed in the above protocol was chosen, to pretreat (0.5-24 h) different
      groups of animals. The studied parameters were evaluated 4 and 48 h after
      pleurisy induction. 3. Acute administration of theophylline (1-50 mg kg-1, i.p.)
      cromolyn (0.02-0.2 mg per pleural cavity) and salbutamol (0.5-50 mg kg-1, i.p.),
      30 min prior to carrageenin, caused significant inhibition of total cell and
      fluid leakage in the pleural cavity at 4 h (P < 0.01). All drugs exerted a long
      lasting inhibitory effect on both exudation and cell migration (P < 0.01) when
      administered 0.5-8 h before pleurisy induction. However, the temporal profile of
      the inhibitory effect induced by these drugs on the first phase of the
      inflammatory reaction was clearly different. Thus, the inhibitory effect induced
      by theophylline and cromolyn on exudation was significantly longer (up to 24 h)
      in comparison to their effects on cell migration (only up to 8 h). In contrast,
      although salbutamol when administered 30 min before pleurisy induction abolished
      fluid leakage (P < 0.01), this effect was not sustained in the groups pretreated
      for 4-8 h. In these latter groups, a significant but much smaller reduction of
      exudation was observed (P < 0.01), whereas the magnitude of cell migration
      inhibition did not vary. 4. The second phase (48 h) of the inflammatory reaction
      induced by carrageenin (1%) was significantly inhibited by cromolyn (0.02 mg per
      pleural cavity) when this drug was administered 0.5-24 h before pleurisy
      induction (P < 0.01). Similar results were observed when theophylline (50 mg kg
      1, i.p.) was administered 0.5-4 h before the injection of the phlogistic agent (P
      < 0.01). Treatment of the animals with salbutamol (5 mg kg-1, i.p.), 0.5-24 h
      before pleurisy induction, did not inhibit either cell migration or fluid
      leakage. In this condition, a significant increase of these parameters was
      observed in the group pretreated with salbutamol 8-24 h before pleurisy induction
      (P < 0.01). 5. These results indicate that theophylline and cromolyn were able to
      inhibit the early (4 h) and late (48 h) phases of the inflammatory reaction
      induced by carrageenin in a murine model of pleurisy. Salbutamol was effective
      only against the early phase. The inhibitory effects of theophylline, cromolyn
      and salbutamol on the early phase of this inflammatory reaction were long
      lasting, although a distinct profile of inhibition was observed among them. These
      findings confirm and extend previous results described in other models of asthma
      and support both clinical and experimental evidence suggesting that these anti
      asthmatic agents exhibit marked anti-inflammatory properties.

PMID- 8762114
TI  - The case for living wills.

PMID- 8762115
TI  - Don't treat me; do treat me: against living wills.

PMID- 8762113
TI  - Heterogeneous distribution of benzodiazepine receptors among rat neostriatal
      neurones.
AB  - 1. The effects of benzodiazepine receptor (BZR) agonist were investigated in
      dissociated rat neostriatal neurones by a conventional whole-cell patch recording
      configuration at room temperature. 2. The dissociated neurones, with a longest
      somatic diameter of larger than 25 microns, were classified as 'large neurones',
      while those having soma measuring less than 15 microns were described as 'small
      neurones'. Large neurones were intensely positive for acetylcholinesterase
      staining, whereas the small ones were not. 3. CL218,872 enhanced the GABA
      response in both the large and small neurones with similar EC50S. However, the
      potentiation efficacy of CL218,872 in large neurones was larger than that of
      small ones. 4. Zolpidem also potentiated the GABA response in both neuronal
      populations with similar EC50S. This compound also enhanced the GABA response
      more strongly in large neurones than in small ones. 5. Zopiclone exerted a
      prominent potentiation in large neurones, although no difference was seen in the
      EC50S in the large and small neurones. 6. It was concluded that the BZR in large
      neurones had a different pharmacological property from that in small ones and
      that the BZR agonists showed a prominent difference, not in EC50, but in the
      potentiation efficacy between these neuronal populations.

PMID- 8762116
TI  - Cataract: current management.
AB  - Current management of cataract is aimed at assessing the impact of cataract on
      the quality of life and determining the role of surgical correction in the
      context of the expected surgical complications.

PMID- 8762117
TI  - Sedation and sedative drugs in paediatrics.
AB  - The first article in this series looked at the provision of analgesia in
      paediatric practice. Practical procedures are common in paediatric practice.
      Certain procedures may be painful or distressing to the child if undertaken in
      the absence of sedation or analgesia. This article reviews the practical
      considerations which arise from the use of sedative drugs in children and looks
      at some of the drugs available.

PMID- 8762118
TI  - Can we improve diuretic response in heart failure?
AB  - Although there have been major advances in the treatment of heart failure, loop
      diuretics remain essential for the treatment of fluid retention. Patients with
      refractory heart failure become resistant to progressively larger doses of
      diuretics. Some of the strategies which may be helpful in restoring diuretic
      efficacy are reviewed.

PMID- 8762119
TI  - Management of epilepsy in pregnancy: therapeutic aspects.
AB  - Epilepsy is one of the most common chronic illnesses encountered by
      obstetricians, affecting around 1 in 200 women attending antenatal clinics.
      Epilepsy and antiepileptic drugs may have significant effects on pregnancy and
      pregnancy may affect the epilepsy. It is therefore vital that those looking after
      these women have a knowledge of the potential problems.

PMID- 8762120
TI  - Pass the Royal College examinations: effective essay technique.

PMID- 8762121
TI  - A hypertensive parturient with a supraventricular tachycardia.

PMID- 8762122
TI  - Investigation and staging of lung cancer.

PMID- 8762123
TI  - The surgical management of lung cancer.

PMID- 8762124
TI  - New drugs for the management of lung cancer.

PMID- 8762125
TI  - Radiotherapy in the treatment of lung cancer.

PMID- 8762126
TI  - Vasculitic neuropathy.
AB  - Vasculitic neuropathy usually receives only a footnote in neurology textbooks.
      The condition is rare, but as it is potentially treatable it merits wider
      discussion. This article discusses the pathological features, clinical features
      and associations of vasculitic neuropathy. It recommends a scheme for
      investigating patients and summarizes treatment and prognosis.

PMID- 8762127
TI  - Atheroembolic disease.
AB  - Atheroembolism is becoming an increasingly common cause of renal failure in
      people with widespread atheromatous disease. It remains a diagnosis that is often
      missed, or made only at postmortem. An awareness of risk factors and a high index
      of suspicion will allow it to be recognized more often.

PMID- 8762128
TI  - How to get a job in medicine: 2.
AB  - The purpose of your curriculum vitae (see Vol 55(9) 1996, p.546) was to get you
      shortlisted for the job you want. Now you have to plan how to win that post at
      interview. Careful preparation is necessary. You need to learn about the post,
      the hospital(s), revise likely questions and practise your interview technique.

PMID- 8762129
TI  - Sinusitis, the orbit and visual complications.

PMID- 8762130
TI  - A-Z of management and finance in the NHS: outcomes and use of resources.
AB  - In general, clinical outcomes are the product of clinical practice and good
      outcomes are associated with the judicious application of the best available
      evidence of what constitutes good practice. From the patient's viewpoint this
      application needs to be tempered by personal choice, cultural beliefs, and
      questions of optimal time and location of treatment.

PMID- 8762131
TI  - Protein folding for realists: a timeless phenomenon.
AB  - Future research on protein folding must confront two serious dilemmas. (1) It may
      never be possible to observe at high resolution the very important structures
      that form in the first few milliseconds of the refolding reaction. (2) The energy
      functions used to predict structure from sequence will always be approximations
      of the true energy function. One strategy to resolve both dilemmas is to view
      protein folding from a different perspective, one that no longer emphasizes time
      and unique trajectories through conformation space. Instead, free energy replaces
      time as the reaction coordinate, and ensembles of equilibrium states of partially
      folded proteins are analyzed in place of trajectories of one protein chain
      through conformation space, either in vitro or in silico. Initial
      characterization of the folding of staphylococcal nuclease within this
      alternative conceptual framework has led to an equilibrium folding pathway with
      several surprising features. In addition to the finding of two bundles of four
      hydrophobic segments containing both native and non-native interactions, a
      gradient in relative stability of different substructures has been identified,
      with the most stable interactions located toward the amino terminus and the least
      stable toward the carboxy terminus. Hydrophobic bundles with up-down topology and
      stability gradients may be two examples of numerous tactics used by proteins to
      facilitate rapid folding and minimize aggregation. As NMR methods for structural
      analysis of partially folded proteins are refined, higher resolution descriptions
      of the structure and dynamics of the polypeptide chain outside the native state
      may provide many insights into the processes and energetics underlying the self
      assembly of folded structure.

PMID- 8762132
TI  - Derivation of 3D coordinate templates for searching structural databases:
      application to Ser-His-Asp catalytic triads in the serine proteinases and
      lipases.
AB  - It is well established that sequence templates (e.g., PROSITE) and databases are
      powerful tools for identifying biological function and tertiary structure for an
      unknown protein sequence. Here we describe a method for automatically deriving 3D
      templates from the protein structures deposited in the Brookhaven Protein Data
      Bank. As an example, we describe a template derived for the Ser-His-Asp catalytic
      triad found in the serine proteases and triacylglycerol lipases. We find that the
      resultant template provides a highly selective tool for automatically
      differentiating between catalytic and noncatalytic Ser-His-Asp associations. When
      applied to nonproteolytic proteins, the template picks out two "non-esterase"
      catalytic triads that may be of biological relevance. This suggests that the
      development of databases of 3D templates, such as those that currently exist for
      protein sequence templates, will help identify the functions of new protein
      structures as they are determined and pinpoint their functionally important
      regions.

PMID- 8762133
TI  - An unusual route to thermostability disclosed by the comparison of Thermus
      thermophilus and Escherichia coli inorganic pyrophosphatases.
AB  - The structures of Escherichia coli soluble inorganic pyrophosphatase (E-PPase)
      and Thermus thermophilus soluble inorganic pyrophosphatase (T-PPase) have been
      compared to find the basis for the superior thermostability of T-PPase. Both
      enzymes are D3 hexamers and crystallize in the same space group with very similar
      cell dimensions. Two rather small changes occur in the T-PPase monomer: a
      systematic removal of Ser residues and insertion of Arg residues, but only in the
      C-terminal part of the protein, and more long-range ion pairs from the C-terminal
      helix to the rest of the molecule. Apart from the first five residues, the three
      dimensional structures of E-PPase and T-PPase monomers are very similar. The one
      striking difference, however, is in the oligomeric interactions. In comparison
      with an E-PPase monomer, each T-PPase monomer is skewed by about 1 A in the xy
      plane, is 0.3 A closer to the center of the hexamer in the z direction, and is
      rotated by approximately 7 degrees about its center of gravity. Consequently,
      there are a number of additional hydrogen bond and ionic interactions, many of
      which form an interlocking network that covers all of the oligomeric surfaces.
      The change can also be seen in local distortions of three small loops involved in
      the oligomeric interfaces. The complex rigid-body motion has the effect that the
      hexamer is more tightly packed in T-PPase: the amount of surface area buried upon
      oligomerization increases by 16%. The change is sufficiently large to account for
      all of the increased thermostability of T-PPase over E-PPase and further supports
      the idea that bacterial PPases, most active as hexamers or tetramers, achieve a
      large measure of their stabilization through oligomerization. Rigid-body motions
      of entire monomers to produce tighter oligomers may be yet another way in which
      proteins can be made thermophilic.

PMID- 8762134
TI  - Mobile unnatural amino acid side chains in the core of staphylococcal nuclease.
AB  - The structures of several variants of staphylococcal nuclease with long flexible
      unnatural amino acid side chains in the hydrophobic core have been determined by
      X-ray crystallography. The unnatural amino acids are disulfide moieties between
      the lone cysteine residue in V23C nuclease and methane, ethane, 1-n-propane, 1-n
      butane, 1-n-pentane, and 2-hydroxyethyl thiols. We have examined changes in the
      core packing of these mutants. Side chains as large as the 1-n-propyl cysteine
      disulfide can be incorporated without perturbation of the structure. This is due,
      in part, to cavities present in the wild-type protein. The longest side chains
      are not well defined, even though they remain buried within the protein interior.
      These results suggest that the enthalpy-entropy balance that governs the rigidity
      of protein interiors favors tight packing only weakly. Additionally, the tight
      packing observed normally in protein interiors may reflect, in part, the limited
      numbers of rotamers available to the natural amino acids.

PMID- 8762135
TI  - Tyrosine 8 contributes to catalysis but is not required for activity of rat liver
      glutathione S-transferase, 1-1.
AB  - Reaction of rat liver glutathione S-transferase, isozyme 1-1, with 4
      (fluorosulfonyl)benzoic acid (4-FSB), a xenobiotic substrate analogue, results in
      a time-dependent inactivation of the enzyme to a final value of 35% of its
      original activity when assayed at pH 6.5 with 1-chloro-2,4-dinitrobenzene (CDNB)
      as substrate. The rate of inactivation exhibits a nonlinear dependence on the
      concentration of 4-FSB from 0.25 mM to 9 mM, characterized by a KI of 0.78 mM and
      kmax of 0.011 min-1. S-Hexylglutathione or the xenobiotic substrate analogue, 2,4
      dinitrophenol, protects against inactivation of the enzyme by 4-FSB, whereas S
      methylglutathione has little effect on the reaction. These experiments indicate
      that reaction occurs within the active site of the enzyme, probably in the
      binding site of the xenobiotic substrate, close to the glutathione binding site.
      Incorporation of [3,5-3H]-4-FSB into the enzyme in the absence and presence of S
      hexylglutathione suggests that modification of one residue is responsible for the
      partial loss of enzyme activity. Tyr 8 and Cys 17 are shown to be the reaction
      targets of 4-FSB, but only Tyr 8 is protected against 4-FSB by S
      hexylglutathione. DTT regenerates cysteine from the reaction product of cysteine
      and 4-FSB, but does not reactivate the enzyme. These results show that
      modification of Tyr 8 by 4-FSB causes the partial inactivation of the enzyme. The
      Michaelis constants for various substrates are not changed by the modification of
      the enzyme. The pH dependence of the enzyme-catalyzed reaction of glutathione
      with CDNB for the modified enzyme, as compared with the native enzyme, reveals an
      increase of about 0.9 in the apparent pKa, which has been interpreted as
      representing the ionization of enzyme-bound glutathione; however, this pKa of
      about 7.4 for modified enzyme remains far below the pK of 9.1 for the -SH of free
      glutathione. Previously, it was considered that Tyr 8 was essential for GST
      catalysis. In contrast, we conclude that Tyr 8 facilitates the ionization of the
      thiol group of glutathione bound to glutathione S-transferase, but is not
      required for enzyme activity.

PMID- 8762136
TI  - Self-consistently optimized statistical mechanical energy functions for sequence
      structure alignment.
AB  - A quantitative form of the principle of minimal frustration is used to obtain
      from a database analysis statistical mechanical energy functions and gap
      parameters for aligning sequences to three-dimensional structures. The analysis
      that partially takes into account correlations in the energy landscape improves
      upon the previous approximations of Goldstein et al. (1994, 1995) (Goldstein R,
      Luthey-Schulten Z, Wolynes P, 1994, Proceedings of the 27th Hawaii International
      Conference on System Sciences. Los Alamitos, California: IEEE Computer Society
      Press. pp 306-315; Goldstein R, Luthey-Schulten Z, Wolynes P, 1995, In: Elber R,
      ed. New developments in theoretical studies of proteins. Singapore: World
      Scientific). The energy function allows for ordering of alignments based on the
      compatibility of a sequence to be in a given structure (i.e., lowest energy) and
      therefore removes the necessity of using percent identity or similarity as
      scoring parameters. The alignments produced by the energy function on distant
      homologues with low percent identity (less than 21%) are generally better than
      those generated with evolutionary information. The lowest energy alignment
      generated with the energy function for sequences containing prosite signatures
      but unknown structures is a structure containing the same prosite signature,
      providing a check on the robustness of the algorithm. Finally, the energy
      function can make use of known experimental evidence as constraints within the
      alignment algorithm to aid in finding the correct structural alignment.

PMID- 8762137
TI  - Direct evidence for a two-state protein unfolding transition from hydrogen
      deuterium exchange, mass spectrometry, and NMR.
AB  - We use mass spectrometry in conjunction with hydrogen-deuterium exchange and NMR
      to characterize the conformational dynamics of the 62-residue IgG binding domain
      of protein L under conditions in which the native state is marginally stable.
      Mass spectra of protein L after short incubations in D2O reveal the presence of
      two distinct populations containing different numbers of protected protons. NMR
      experiments indicate that protons in the hydrophobic core are protected in one
      population, whereas all protons are exchanged for deuterons in the other. As the
      exchange period is increased, molecules are transferred from the former
      population to the latter. The absence of molecules with a subset of the core
      protons protected suggests that exchange occurs in part via a highly concerted
      transition to an excited state in which all protons exchange rapidly with
      deuterons. A steady increase in the molecular weight of the population with
      protected protons, and variation in the exchange rates of the individual
      protected protons indicates the presence of an additional exchange mechanism. A
      simple model in which exchange results from rapid (> 10(5)/s) local fluctuations
      around the native state superimposed upon transitions to an unfolded excited
      state at approximately 0.06/s is supported by qualitative agreement between the
      observed mass spectra and the mass spectra simulated according to the model using
      NMR-derived estimates of the proton exchange rates.

PMID- 8762138
TI  - Improving the quality of NMR and crystallographic protein structures by means of
      a conformational database potential derived from structure databases.
AB  - A new conformational database potential involving dihedral angle relationships in
      databases of high-resolution highly refined protein crystal structures is
      presented as a method for improving the quality of structures generated from NMR
      data. The rationale for this procedure is based on the observation that
      uncertainties in the description of the nonbonded contacts present a key limiting
      factor in the attainable accuracy of protein NMR structures and that the
      nonbonded interaction terms presently used have poor discriminatory power between
      high- and low-probability local conformations. The idea behind the conformational
      database potential is to restrict sampling during simulated annealing refinement
      to conformations that are likely to be energetically possible by effectively
      limiting the choices of dihedral angles to those that are known to be physically
      realizable. In this manner, the variability in the structures produced by this
      method is primarily a function of the experimental restraints, rather than an
      artifact of a poor nonbonded interaction model. We tested this approach with the
      experimental NMR data (comprising an average of about 30 restraints per residue
      and consisting of interproton distances, torsion angles, 3JHN alpha coupling
      constants, and 13C chemical shifts) used previously to calculate the solution
      structure of reduced human thioredoxin (Qin J, Clore GM, Gronenborn AM, 1994,
      Structure 2:503-522). Incorporation of the conformational database potential into
      the target function used for refinement (which also includes terms for the
      experimental restraints, covalent geometry, and nonbonded interactions in the
      form of either a repulsive, repulsive-attractive, or 6-12 Lennard-Jones
      potential) results in a significant improvement in various quantitative measures
      of quality (Ramachandran plot, side-chain torsion angles, overall packing). This
      is achieved without compromising the agreement with the experimental restraints
      and the deviations from idealized covalent geometry that remain within
      experimental error, and the agreement between calculated and observed 1H chemical
      shifts that provides an independent NMR parameter of accuracy. The method is
      equally applicable to crystallographic refinement, and should be particular
      useful during the early stages of either an NMR or crystallographic structure
      determination and in cases where relatively few experimental restraints can be
      derived from the measured data (due, for example, to broad lines in the NMR
      spectra or to poorly diffracting crystals).

PMID- 8762139
TI  - The heme redox center of chloroplast cytochrome f is linked to a buried five
      water chain.
AB  - The crystal structure of the 252-residue lumen-side domain of reduced cytochrome
      f, a subunit of the proton-pumping integral cytochrome b6f complex of oxygenic
      photosynthetic membranes, was determined to a resolution of 1.96 A from crystals
      cooled to -35 degrees. The model was refined to an R-factor of 15.8% with a 0.013
      A RMS deviation of bond lengths from ideality. Compared to the structure of
      cytochrome f at 20 degrees, the structure at -35 degrees has a small change in
      relative orientation of the two folding domains and significantly lower isotropic
      temperature factors for protein atoms. The structure revealed an L-shaped array
      of five buried water molecules that extend in two directions from the N delta 1
      of the heme ligand His 25. The longer branch extends 11 A within the large
      domain, toward Lys 66 in the prominent basic patch at the top of the large
      domain, which has been implicated in the interaction with the electron acceptor,
      plastocyanin. The water sites are highly occupied, and their temperature factors
      are comparable to those of protein atoms. Virtually all residues that form
      hydrogen bonds with the water chain are invariant among 13 known cytochrome f
      sequences. The water chain has many features that optimize it as a proton wire,
      including insulation from the protein medium. It is suggested that this chain may
      function as the lumen-side exit port for proton translocation by the cytochrome
      b6f complex.

PMID- 8762140
TI  - The proteins encoded by the rbs operon of Escherichia coli: I. Overproduction,
      purification, characterization, and functional analysis of RbsA.
AB  - The nucleotide-binding component of the high-affinity ribose transport system of
      Escherichia coli, RbsA, was overproduced from a T7-7 expression vector, and the
      protein was purified. Biochemical analyses of the purified protein indicated that
      the ATP analogues, 5'-FSBA and 8-azido ATP, covalently labeled the protein, a
      reaction that was inhibited by ATP, but not by GTP or CTP. The pure protein
      exhibited low-level ATPase activity with a K(m) of about 140 microM. Analyses of
      bacterial strains carrying chromosomal deletions of rbsA and other rbs genes
      suggested that RbsA is important for the chemotaxis function, a surprising result
      that was not anticipated from previous studies. However, an inconsistency between
      the several results from deletion strains raises questions regarding the
      interpretations of the in vivo data.

PMID- 8762141
TI  - The proteins encoded by the rbs operon of Escherichia coli: II. Use of chimeric
      protein constructs to isolate and characterize RbsC.
AB  - Chimeric genes encoding full-length copies of rbsA and rbsC connected by segments
      coding for short bridge peptides were constructed and expressed in Escherichia
      coli. Surprisingly, the chimeric genes complemented the strain in which rbsA and
      rbsC were deleted. The chimeric proteins were overproduced, and the products were
      purified by affinity chromatography. In order to obtain highly purified protein,
      a poly-His leader peptide was incorporated so that Ni-chelate affinity
      chromatography could be employed. The leader peptide and the bridge peptide were
      designed with factor Xa-cleavable sites to permit recovery of the individual RbsA
      and RbsC protein. A rbsC gene encoding a poly-His leader was also constructed and
      expressed. Both the chimeric RbsA-C species and the poly-HisRbsC were produced at
      levels that permitted isolation of the equivalent of milligram quantities of RbsC
      per liter of culture. This is a substantial increase in amounts from any previous
      RbsC production vectors. All proteins from the rbs operon have now been
      overproduced and substantially purified.

PMID- 8762142
TI  - Intrinsic tryptophans of CRABPI as probes of structure and folding.
AB  - The native state fluorescence and CD spectra of the predominantly beta-sheet
      cellular retinoic acid-binding protein I (CRABPI) include contributions from its
      three tryptophan residues and are influenced by the positions of these residues
      in the three-dimensional structure. Using a combination of spectroscopic
      approaches and single Trp-mutants of CRABPI, we have deconvoluted these spectra
      and uncovered several features that have aided in our analysis of the development
      of structure in the folding pathway of CRABPI. The emission spectrum of native
      CRABPI is dominated by Trp 7. Trp 109 is fluorescence-silent due to its
      interaction with the guanidino group of Arg 111. Although the far-UV CD spectrum
      of CRABPI is largely determined by the protein's secondary structure, aromatic
      clustering around Trp 87 and the aromatic-charge interaction between Arg 111 and
      Trp 109 give rise to a characteristic feature in the CD spectrum at 228 nm. The
      near-UV CD bands of CRABPI arise largely from additive contributions of the three
      tryptophan residues. Trp 7 and Trp 87 give a negative CD band at 275 nm. The near
      UV CD band from Trp 109 is positive and shifted to longer wavelengths (to 302 nm)
      due to the charge-aromatic interaction between Arg 111 and Trp 109. Our
      deconvolution of the equilibrium spectra have been used to interpret kinetic
      folding experiments monitored by stopped-flow fluorescence. These dynamic
      experiments suggest the early evolution of a well-populated, hydrophobically
      collapsed intermediate, which undergoes global rearrangement to form the fully
      folded structure. The results presented here suggest several additional
      strategies for dissecting the folding pathway of CRABPI.

PMID- 8762143
TI  - Secondary structure and NMR assignments of Bacillus circulans xylanase.
AB  - Bacillus circulans xylanase (BCX) is a member of the family of low molecular
      weight endo-beta-(1,4)-xylanases. The main-chain 1H, 13C, and 15N resonances of
      this 20.4-kDa enzyme were assigned using heteronuclear NMR experiments recorded
      on a combination of selectively and uniformly labeled protein samples. Using
      chemical shift, NOE, J coupling, and amide hydrogen exchange information, 14 beta
      strands, arranged in a network of three beta-sheets, and a single alpha-helix
      were identified in BCX. The NMR-derived secondary structure and beta-sheet
      topology agree closely with that observed in the crystal structure of this
      protein. The HN of Ile 118 has a strongly upfield-shifted resonance at 4.03 ppm,
      indicative of a potential amide-aromatic hydrogen bond to the indole ring of Trp
      71. This interaction, which is conserved in all low molecular weight xylanases of
      known structure, may play an important role in establishing the active site
      conformation of these enzymes. Following hen egg white and bacteriophage T4
      lysozymes, B. circulans xylanase represents the third family of beta-glycanases
      for which extensive NMR assignments have been reported. These assignments provide
      the background for detailed studies of the mechanism of carbohydrate recognition
      and hydrolysis by this bacterial xylanase.

PMID- 8762144
TI  - Invariant glycines and prolines flanking in loops the strand beta 2 of various
      (alpha/beta)8-barrel enzymes: a hidden homology?
AB  - The question of parallel (alpha/beta)8-barrel fold evolution remains unclear,
      owing mainly to the lack of sequence homology throughout the amino acid sequences
      of (alpha/beta)8-barrel enzymes. The "classical" approaches used in the search
      for homologies among (alpha/beta)8-barrels (e.g., production of structurally
      based alignments) have yielded alignments perfect from the structural point of
      view, but the approaches have been unable to reveal the homologies. These are
      proposed to be "hidden" in (alpha/beta)8-barrel enzymes. The term "hidden
      homology" means that the alignment of sequence stretches proposed to be
      homologous need not be structurally fully satisfactory. This is due to the very
      long evolutionary history of all (alpha/beta)8-barrels. This work identifies so
      called hidden homology around the strand beta 2 that is flanked by loops
      containing invariant glycines and prolines in 17 different (alpha/beta)8-barrel
      enzymes, i.e., roughly in half of all currently known (alpha/beta)8-barrel
      proteins. The search was based on the idea that a conserved sequence region of an
      (alpha/beta)8-barrel enzyme should be more or less conserved also in the
      equivalent part of the structure of the other enzymes with this folding motif,
      given their mutual evolutionary relatedness. For this purpose, the sequence
      region around the well-conserved second beta-strand of alpha-amylase flanked by
      the invariant glycine and proline (56_GFTAIWITP, Aspergillus oryzae alpha-amylase
      numbering), was used as the sequence-structural template. The proposal that the
      second beta-strand of (alpha/beta)8-barrel fold is important from the
      evolutionary point of view is strongly supported by the increasing trend of the
      observed beta 2-strand structural similarity for the pairs of (alpha/beta)8
      barrel enzymes: alpha-amylase and the alpha-subunit of tryptophan synthase, alpha
      amylase and mandelate racemase, and alpha-amylase and cyclodextrin
      glycosyltransferase. This trend is also in agreement with the existing
      evolutionary division of the entire family of (alpha/beta)8-barrel proteins.

PMID- 8762145
TI  - Substrate-induced conformational changes in yeast 3-phosphoglycerate kinase
      monitored by fluorescence of single tryptophan probes.
AB  - 3-Phosphoglycerate kinase (PGK) catalyzes the reversible conversion of 3
      phosphoglycerate (3-PG) and ATP to 1,3-diphosphoglycerate (1,3-diPG) and ADP in
      the presence of magnesium ions. PGK is a single polypeptide chain arranged in two
      domains, with an active site located in the interdomain cleft. The large distance
      between the binding sites for 3-PG and ATP, deduced from the crystallographic
      structures of the binary complexes, gave rise to the hypothesis that this enzyme
      undergoes a hinge-bending domain motion from open to closed conformation during
      catalysis. However, no direct experimental evidence exists for the "closed"
      conformation in the presence of both substrates. In this study, several PGK
      mutants with single tryptophans placed in various location were used as intrinsic
      fluorescent probes to examine the extent and delocalization of conformational
      changes induced by the binding of 3-PG, 1,3-diPG, ADP, ATP, and PNP-AMP
      (nonhydrolyzable analogue of ATP), and by 3-PG and PNP-AMP together. The results
      showed that only the probes situated in the hinge and in parts of each domain
      close to the hinge reflect substrate-induced conformational changes. Binding of
      substrates to one domain was found to induce spectral perturbation of the probes
      in the opposite domain, indicating a transmission of conformational changes
      between the domains. A combination of both substrates generated much larger
      fluorescence changes than the individual substrates. The binding constants were
      determined for each substrate using probes situated in different locations.

PMID- 8762146
TI  - A natural variant of type I antifreeze protein with four ice-binding repeats is a
      particularly potent antifreeze.
AB  - A 4.3-kDa variant of Type I antifreeze protein (AFP9) was purified from winter
      flounder serum by size exclusion chromatography and reversed-phase HPLC. By the
      criteria of mass, amino acid composition, and N-terminal sequences of tryptic
      peptides, this variant is the posttranslationally modified product of the
      previously characterized AFP gene 21a. It has 52 amino acids and contains four 11
      amino acid repeats, one more than the major serum AFP components. The larger
      protein is completely alpha-helical at 0 degree C, with a melting temperature of
      18 degrees C. It is considerably more active as an antifreeze than the three
      repeat winter flounder AFP and the four-repeat yellowtail flounder AFP, both on a
      molar and a mg/mL basis. Several structural features of the four-repeat winter
      flounder AFP, including its larger size, additional ice-binding residues, and
      differences in ice-binding motifs might contribute to its greater activity. Its
      abundance in flounder serum, together with its potency as an antifreeze, suggest
      that AFP9 makes a significant contribution to the overall freezing point
      depression of the host.

PMID- 8762147
TI  - Microheterogeneity of human filaggrin: analysis of a complex peptide mixture
      using mass spectrometry.
AB  - Filaggrin is the product of posttranslational processing of the large, epidermal
      protein profilaggrin, which consists of 10 or more tandem filaggrin domains plus
      an amino and a carboxyl domain. According to fragmentary cDNA sequences, the
      filaggrin domains in the human protein vary at 40% of the amino acid positions;
      hence, mature filaggrin is a population of homologous but heterogeneous proteins,
      even within one individual. Available gene sequences give only a limited picture
      of the heterogeneity of human filaggrin protein because no complete human
      profilaggrin gene has been sequenced. Questions about the extent of heterogeneity
      of filaggrin within and between individuals have not been answered, nor have
      questions concerning the limited proteolytic cleavage of human profilaggrin that
      generates filaggrin in vivo. In order to address these questions and to provide
      an analysis of the primary structure of human filaggrins, we employed various
      methods of mass spectrometry. The intact protein and a tryptic digest of the
      mixture of human filaggrins were examined by matrix-assisted laser desorption
      time-of-flight mass spectrometry. Tryptic digests of human filaggrin from single
      individuals were also separated and analyzed by liquid chromatography/mass
      spectrometry (LC/MS) (using electrospray mass spectrometry), and specific
      peptides were identified by tandem mass spectrometry (MS/MS). A robust data
      analysis program, Sherpa, was developed to facilitate the interpretation of both
      LC/MS and MS/MS. These experiments show that human filaggrin includes
      heterogeneity not yet seen in cDNA sequences, but that much structure is highly
      conserved. Interestingly, we found that the heterogeneity is conserved among
      individuals. An approximation of the regions linking filaggrins in human
      profilaggrin is developed. These investigations provide a unique test of the
      limits of tryptic mapping of complex mixtures using mass spectrometry.

PMID- 8762148
TI  - In vitro methionine oxidation of Escherichia coli-derived human stem cell factor:
      effects on the molecular structure, biological activity, and dimerization.
AB  - The effect of oxidation of the methionine residues of Escherichia coli-derived
      recombinant human stem cell factor (huSCF) to methionine sulfoxide on the
      structure and activity of SCF was examined. Oxidation was performed using
      hydrogen peroxide under acidic conditions (pH 5.0). The kinetics of oxidation of
      the individual methionine residues was determined by quantitation of oxidized and
      unoxidized methionine-containing peptides, using RP-HPLC of Asp-N endoproteinase
      digests. The initial oxidation rates for Met159, Met-1, Met27, Met36, and Met48
      were 0.11 min-1, 0.098 min-1, 0.033 min-1, 0.0063 min-1, and 0.00035 min-1,
      respectively, when SCF was incubated in 0.5% H2O2 at room temperature. Although
      oxidation of these methionines does not affect the secondary structure of SCF,
      the oxidation of Met36 and Met48 affects the local structure as indicated by CD
      and fluorescence spectroscopy. The 295-nm Trp peak in the near-UV CD is decreased
      upon oxidation of Met36, and lost completely following the oxidation of Met48,
      indicating that the Trp44 environment is becoming significantly less rigid than
      it is in native SCF. Consistent with this result, the fluorescence spectra
      revealed that Trp44 becomes more solvent exposed as the methionines are oxidized,
      with the hydrophobicity of the Trp44 environment decreasing significantly. The
      oxidations of Met36 and Met48 decrease biological activity by 40% and 60%,
      respectively, while increasing the dissociation rate constant of SCF dimer by two
      and threefold. These results imply that the oxidation of Met36 and Met48 affects
      SCF dimerization and tertiary structure, and decreases biological activity.

PMID- 8762149
TI  - Crystal structure of two new bifunctional nonsubstrate type thrombin inhibitors
      complexed with human alpha-thrombin.
AB  - The crystal structures of two new thrombin inhibitors, P498 and P500, complexed
      with human alpha-thrombin have been determined at 2.0 A resolution and refined to
      crystallographic R-factors of 0.170 and 0.169, respectively. These compounds,
      with picomolar binding constants, belong to a family of potent bifunctional
      inhibitors that bind thrombin at two remote sites: the active site and the
      fibrinogen recognition exosite (FRE). The inhibitors incorporate a nonsubstrate
      type active site binding fragment: Dansyl-Arg-(D)Pipecolic acid (Dns-Arg-(D)Pip),
      reminiscent of the active-site directed inhibitors MD-805 and MQPA, rendering
      them resistant to thrombin-induced hydrolysis. The FRE binding fragment of these
      inhibitors corresponds to the hirudin55-65 sequence. They differ in the chemical
      nature of the nonpeptidyl linker bridging these two functional activities. In
      both cases, the active site binding fragment is well defined in the electron
      density. The DnsH1, ArgH2, and (D)PipH3 groups occupy the S3, S1, and S2 subsites
      of thrombin, respectively, in a way similar to that observed in the thrombin-MQPA
      complexes. Binding in the active site of thrombin is characterized by numerous
      van der Waals contacts and ring-ring system interactions. Unlike in the substrate
      like inhibitors, ArgH2 enters the S1 specificity pocket from the P2 position and
      adopts a bent conformation to make an hydrogen bond to the carboxylate of Asp189.
      In this noncanonical position, its carbonyl points away from the oxyanion hole,
      which is now occupied by well-ordered solvent molecules. The linkers fit in the
      groove extending from the active site to the FRE. The C-terminal fragments of
      both inhibitors bind in the same way as analogous FRE binding elements in
      previously described complexes.

PMID- 8762151
TI  - Preliminary crystallographic analysis of the oxidized form of a two mono-nuclear
      iron centres protein from Desulfovibrio desulfuricans ATCC 27774.
AB  - Crystals of the fully oxidized form of desulfoferrodoxin were obtained by vapor
      diffusion from a solution containing 20% PEG 4000, 0.1 M HEPES buffer, pH 7.5,
      and 0.2 M CaCl2. Trigonal and/or rectangular prisms could be obtained, depending
      on the temperature used for the crystal growth. Trigonal prisms belong to the
      rhombohedral space group R32, with a = 112.5 A and c = 63.2 A; rectangular prisms
      belong to the monoclinic space group C2, with a = 77.7 A, b = 80.9 A, c = 53.9 A,
      and beta = 98.1 degrees. The crystallographic asymmetric unit of the rhombohedral
      crystal form contains one molecule. There are two molecules in the asymmetric
      unit of the monoclinic form, in agreement with the self-rotation function.

PMID- 8762150
TI  - Tumor marker disaccharide D-Gal-beta 1, 3-GalNAc complexed to heat-labile
      enterotoxin from Escherichia coli.
AB  - Heat-labile enterotoxin (LT) is part of the cholera toxin (CT) family and
      consists of a catalytic A subunit and a B pentamer that serves to recognize the
      oligosaccharide part of the GM1 ganglioside receptor. We report here the crystal
      structure of heat-labile enterotoxin in complex with the disaccharide portion of
      the Thomsen-Friedenreich (T-antigen) tumor marker. The toxin:carbohydrate complex
      is determined to 2.13 A resolution, yielding an R-factor of 18.5%. The T-antigen
      disaccharide, D-Gal-beta 1,3-GalNAc-Ser/Thr, is present in more than 85% of human
      carcinomas and monitoring its autoimmune response is used for the early detection
      of tumors. Insight into the molecular recognition of this tumor antigen by sugar
      binding proteins can benefit the development of a diagnostic tool for human
      carcinomas as well as a T-antigen directed anticancer drug delivery system.

PMID- 8762152
TI  - Subcloning of a DNA fragment encoding a single cohesin domain of the Clostridium
      thermocellum cellulosome-integrating protein CipA: purification, crystallization,
      and preliminary diffraction analysis of the encoded polypeptide.
AB  - An Escherichia coli clone encoding a single cohesin domain of the cellulosome
      integrating protein CipA from Clostridium thermocellum was constructed, and the
      corresponding polypeptide was purified, treated with papain, and crystallized
      from a PEG 8000 solution. Crystals exhibit orthorhombic symmetry, space group
      P2(1)2(1)2(1), with cell dimensions a = 37.7 A, b = 80.7 A, c = 93.3 A, and four
      or eight molecules in the unit cell. The crystals diffract X-rays to beyond 2 A
      resolution and are suitable for further crystallographic studies.

PMID- 8762153
TI  - Flexibility of DNA binding domain of trp repressor required for recognition of
      different operator sequences.
AB  - Trp repressor (25 kDa) is a regulatory protein that controls transcription
      initiation in the tryptophan biosynthetic operon and at least four other operons
      in Escherichia coli. An alanine to valine mutation (AV77) in the DNA binding
      domain is known to increase repressor activity at the trp operator in vivo, but
      not in vitro. We report here the amide proton exchange rates for the DNA-binding
      domains of both the wild-type and AV77 proteins. We find that the alanine to
      valine change stabilizes the flexible DNA-binding domain of the repressor. We
      present in vivo data showing that, although the AV77 repressor is more inhibitory
      at the trp operator than the wild-type repressor, it does not have increased
      activity at the aroH or trpR operator; repression at the aroH operator is, in
      fact, reduced. Our results suggest that the flexibility exhibited by the wild
      type repressor allows a broader range of repressor/DNA interactions, whereas the
      increased rigidity resulting from the AV77 change limits the repressor's
      effectiveness at some operators.

PMID- 8762154
TI  - Crystallization of the A alpha subunit of protein phosphatase 2A.
AB  - The A alpha subunit of human protein phosphatase 2A forms crystals in space group
      P2(1) with cell dimensions a = 104.0, b = 174.9, c = 168.2 A, and beta angle =
      90.2 degrees. At cryogenic temperatures, the crystals diffracted to a resolution
      limit of approximately 3.0 A. Based on the unit cell dimensions and a calculated
      molecular mass of 65,277 Da, the Matthews coefficient suggests eight molecules
      per asymmetric unit. Two native data sets were collected to a nominal resolution
      of 3.0 A and merged to provide a set that is 93% complete, with Rsym of 9.9%.

PMID- 8762155
TI  - In search of dihydrofolate reductase.

PMID- 8762156
TI  - Psychopharmacology of memory modulation: evidence for multiple interaction among
      neurotransmitters and hormones.
AB  - Experimental results are reviewed which indicate that memory storage can be
      altered by a number of post-training treatments that affect different hormones
      and neurotransmitters. Moreover, evidence was reported which suggests that the
      action of treatments effective on memory processes involves interactions among
      different systems, consistently with the complexity of brain systems. In the last
      decade, inbred strains have been exploited to investigate the role of
      neurotransmitter and hormone systems in learning and memory, leading to
      behavioural and neurochemical correlations based on strain differences that
      provide unique information on the biological systems underlying behaviour.
      Research carried out on the inbred strains of mice C57BL/6 (C57) and DBA/2 (DBA),
      demonstrates that the genetic makeup plays an important role in modulating
      response to drug administration. Thus, recent results have shown that in C57
      mice, similarly to what occurs in outbred strains of mice or in rats, GABAergic
      agonists impair memory and antagonists improve it, whilst the opposite is evident
      in the DBA strain. By contrast, post-training administration of selective D1 or
      D2 agonists impairs and post-training administration of selective antagonists
      improves retention in DBA mice, whilst these agents have opposite effects in the
      C57 strain. Dose- and strain-dependent effects are evident also following post
      training corticosterone as well as opioid agonists and antagonists
      administration. On the other side, these two strains react similarly to
      oxotremorine (improvement) and to atropine (impairment) administration, DBA mice
      being more responsive to the effects of both drugs than C57 mice. Data on the
      interactions between agents acting upon different neurotransmitter and/or
      hormonal systems in these strains indicate strain-dependent synergistic or
      antagonistic interactions among some of these systems, pointing to inbred strains
      of mice as an important methodological tool in the study of neural and hormonal
      factors involved in emotion and in its effects on cognition. In particular, these
      studies have been carried out on inbred strains of mice from which recombinant
      inbred (RI) strains are available that have recently been proposed as a choice
      experimental method in psychopharmacogenetics.

PMID- 8762157
TI  - Psychobiology of novelty seeking and drug seeking behavior.
AB  - There is considerable evidence that high novelty seekers are at increased risk
      for using drugs of abuse relative to low novelty seekers. This review examines
      the potential biological mechanism that may help explain the relationship between
      novelty seeking and drug seeking behavior. Evidence is summarized to suggest that
      exposure to novelty activates, at least in part, the same neural substrate that
      mediates the rewarding effects of drugs of abuse. It is argued that individual
      differences in response to novelty and drugs may relate to individual differences
      in the mesolimbic dopamine (DA) system of the brain. Individual differences in
      both novelty seeking and drug seeking behavior, while under some degree of
      genetic control, appear to be modifiable by early development experiences and
      this modification may relate to alterations in activity of the mesolimbic DA
      system. Within the context of this biological formulation, implications for the
      prevention and treatment of drug abuse are discussed.

PMID- 8762158
TI  - The neurophysiological basis of motor imagery.
AB  - Motor imagery may be defined as a dynamic state during which representations of a
      given motor act are internally rehearsed in working memory without any overt
      motor output. What neural processes underlie the generation of motor imagery?
      This paper reviews physiological evidence from measurements of regional brain
      activity and from measurements of autonomic responses in normal subjects and
      behavioral observations from brain damaged patients. It is proposed that motor
      imagery shares neural mechanisms with processes used in motor control. This
      review emphasizes the importance of the prefrontal cortex and its connections to
      the basal ganglia in maintaining dynamic motor representations in working memory.
      This view fits with the general idea that the prefrontal cortex is responsible
      for the creation and maintenance of explicit representations that guide thought
      and action.

PMID- 8762159
TI  - The primate temporal pole: its putative role in object recognition and memory.
AB  - In this article, we consider both the ventral temporopolar cortex and the
      perirhinal cortex (areas 35 and 36) as the anterior ventromedial temporal (aVMT)
      cortex, and discuss its role based on recent data in monkeys and human subjects.
      In monkeys, the aVMT cortex receives its primary input from area TE, and only
      minor input from other cortical areas. Laminar patterns of connections suggest
      that the aVMT cortex is a hierarchically higher-order area than area TE. Lesions
      of this cortex produce deficits in the learning and performance of visual memory
      tasks. Neurons in the aVMT cortex respond selectively to complex stimuli and
      changes in activity related to visual memory tasks. In humans, damage of this
      cortex induces deficits in the recognition of familiar objects and faces. The
      aVMT cortex is activated during recognition of familiar faces. In addition, the
      aVMT cortex is one of the most vulnerable areas in Alzheimer's disease. All these
      data indicate that the aVMT cortex is a higher-order visual cortical area that is
      related to object recognition and memory. The anterior area TE has been
      implicated in both functions. We propose here that these areas and the anterior
      entorhinal cortex are designated as the temporal pole, a brain region which is
      specialized for both object recognition and memory.

PMID- 8762160
TI  - Avoidance and classical conditioning of leg flexion in dogs.
AB  - This study of leg flexion conditioning in dogs, which were trained under both
      avoidance and classical contingencies consecutively, confirmed and extended the
      results from the Wahlsten and Cole study (In Classical Conditioning II: Current
      Research and Theory, Appleton Century-Crofts, New York, 1972). Briefly, dogs were
      trained to asymptotic behavioral levels under either avoidance or classical
      contingencies with a CS-US interval of either three (3) or five (5) seconds where
      the unconditioned stimulus (US) was shock to the foreleg and the conditioned
      stimulus (CS) was 1000 Hz tone. The dogs were then switched to the other
      contingency (without any modification in the stimulus situation other than the
      shock contingency) and trained to asymptotic behavioral levels. The CS remained
      on for the entire CS-US period and terminated with the end of the scheduled
      interval. Under the classical contingency, the US occurred as scheduled on every
      trial regardless of the dog's behavior. Under the avoidance contingency, the US
      was prevented from occurring if the subject responded with a criterion leg lift
      during the CS-US interval. The only feedback to the dog of a successful
      performance was the leg lift itself. The results indicated that there were two
      different conditioned responses produced, one just after CS onset under the
      avoidance contingency, and one just before US onset under the classical
      contingency for both CS-US intervals. The findings were interpreted as supporting
      a single-factor informational view of learning and a neural model was presented.

PMID- 8762161
TI  - Vomeronasal system involvement in response to conspecific odors in adult male
      opossums, Monodelphis domestica.
AB  - The present study was designed to test the hypothesis that preferential nuzzling
      of unfamiliar conspecific odors by male opossums is vomeronasally mediated.
      Opossums were presented with vials containing their own odors (Own) and vials
      with odors from unfamiliar conspecifics (Novel) both before and after (Expt. 1)
      or only after (Expt. 2) vomeronasal nerve (VNNX) or sham (Sham) surgery. Nuzzling
      duration was greater for Novel before (Expt. 1) and after (Expts. 1 and 2)
      surgery both in VNNX and Sham animals, indicating that a functional vomeronasal
      system is not necessary for the differential nuzzling of novel odors. In
      contrast, differential scent marking of Novel was lost following VNNX, but not
      following sham surgery. Since VNNX lesions disrupt differential marking behavior
      but, not differential nuzzling, it is possible that different components of
      conspecific odors guide these two chemosensory behaviors and that these
      components may be detected by different sensory systems. Vomeronasal nerve
      lesions, confirmed histologically, resulted in the loss of the beta-NADPH
      dependent reaction product from the accessory olfactory bulbs (AOB). The pattern
      of staining with 4 lectins, soybean agglutinin (SBA), Phosphocarpus
      tetragonolobus (PCT), Vicia villosa agglutinin (VVA), and Griffonia simplicifolia
      lectin I-isolectin B4 (GS I-B4) remained unchanged in the AOB following
      vomeronasal nerve lesions, although the size of the AOB appeared to decrease in
      the VNNX animals.

PMID- 8762162
TI  - Effect of acetylcholinesterase inhibition on behavior is age-dependent in freely
      moving Aplysia.
AB  - The significance of age-dependent changes in acetylcholinesterase (AChE) activity
      level is poorly understood. Reported here is one approach to understand AChE's
      function as it relates to age: to investigate how inhibition of AChE affects
      behavior in freely moving Aplysia of two age groups, mature and old. The
      siphon/gill withdrawal reflex (S/GWR) and gill pumping movement (GPM) were
      examined to assay the effects of AChE inhibition by BW284c51, a specific and
      reversible AChE inhibitor. In mature Aplysia AChE inhibition by 2 microM and 5
      microM of BW284c51 resulted in a significantly shortened S/GWR duration, and in
      suppression of habituation and dishabituation. In old animals, AChE inhibition by
      2 microM of BW284c51 did not affect S/GWR and only dishabituation was suppressed
      by inhibition by 5 microM of BW284c51. AChE inhibition reduced the GPM rate
      significantly only in mature animals. AChE inhibition did not alter the decrement
      in GPM rate which is regularly observed in both age groups during repetitive
      exposure to acidified sea water. Thus both S/GWR and GPM were affected by AChE
      inhibition, and a significant age effect on the two behaviors was observed.
      Comparisons of the results of AChE inhibition which would elevate acetylcholine
      (ACh) levels with those of carbachol administration revealed that AChE inhibition
      affects both cholinergic and non-cholinergic mechanisms underlying the two
      behaviors.

PMID- 8762163
TI  - Does dendritic growth underly recovery from neonatal occipital lesions in rats.
AB  - Rats were given lesions of visual cortex on postnatal day 4 or 10, or in
      adulthood. Ninety days later they were trained on a horizontal-vertical stripes
      discrimination task and a visual-spatial navigation task. None of the operated
      rats acquired the tasks. The brains were processed for Golgi-Cox staining and
      dendritic arborization was quantified in the layer III pyramidal cells in
      somatosensory cortex. Relative to normal control brains, the neurons of the day 4
      and adult operates showed a reduction in dendritic branching, whereas the neurons
      of the day 10 operates had a significant increase in dendritic arborization. This
      arborization may be related to enhanced somatosensory function but does not
      support recovery of visually-guided behavior.

PMID- 8762164
TI  - Varieties of paw and digit movement during spontaneous food handling in rats:
      postures, bimanual coordination, preferences, and the effect of forelimb cortex
      lesions.
AB  - This study describes how rats use their paws and digits when handling a wide
      range of foodstuffs, including food pellets, grapes, sunflower seeds, shelled and
      unshelled peanuts, and different sized pastas, etc. Analysis of videorecordings
      show that the rats display digit postures that include variations in the spacing
      of the digits, differences in the relative use of different digits, and interlimb
      differences in paw and digit posture. The rats also display limb preferences in
      that one paw is used in a supporting function while the other rotates, flips, or
      pushes the food as is required by the shape of the item. There is a significant
      correlation between the paw used for manipulation and food items of similar shape
      but no correlation between the limb used for manipulation and that used for
      skilled reaching. Small unilateral lesions to the forepaw area of somatic
      sensorimotor cortex produced impairments in use of the paw contralateral to the
      lesions. These results: (1) reveal a surprising complexity in the way in which
      rats use their paws and digits in manipulating food; (2) show that rats have limb
      preferences in spontaneous food handling; and (3) show that manipulatory
      dexterity is dependent upon the integrity of the forelimb area of motor cortex.
      The results are discussed in relation to the evolution of motor skill, the use of
      rats for investigating questions of motor system organization, neural plasticity,
      and recovery of function after brain damage.

PMID- 8762165
TI  - Long-term impoverished housing effects on Morris maze performance after a fimbria
      lesion.
AB  - Male Wistar rats received bilateral Fimbria lesions and were postoperatively
      housed in either standard social conditions or in impoverished conditions (one
      rat per cage) for 2 weeks in experiment I, and for 7 months in experiment II. The
      effects of lesion and housing conditions were investigated in the Morris maze
      spatial orientation task. Fimbria lesions increased the latency to reach the
      platform during acquisition in both experiments, which indicates that functional
      recovery of the Morris maze impairment does not occur in 7 months time. Post
      operative impoverishment for 2 weeks or for 7 months reduced the lesion induced
      deficit in Morris maze acquisition, while it had a more general effect in the
      trial without platform. Interestingly, the impoverishment effects were not more
      severe after 7 months, but even less easily detected. These findings are
      interpreted as if impoverishment effects the reactiveness of animals to external
      stimuli, which may help the animal to compensate for the lesion-induced-deficit
      in Morris maze learning.

PMID- 8762166
TI  - Ventromedial hypothalamic lesions prevent the fasting-induced changes in day
      night pattern of locomotor activity.
AB  - The time-course of day-night organization of running wheel activity during
      prolonged fasting was studied in rats, with or without electrolytic lesions in
      the ventromedial hypothalamus (VMH). For each individual, dates were referenced
      to the metabolic transition from lipid to protein utilization in late fasting;
      this was estimated by daily weighing. In fasted sham-operated controls, daytime
      activity increased progressively over the fast. This fasting-induced rise in
      diurnal activity was not due to daily handling, since it was observed also in non
      handled (fasted) controls. The pattern of the increase in sham-operated rats
      differed between 2-hour periods (8-10 h to 18-20 h). The distribution of
      nocturnal activity was also modified during food deprivation: nocturnal activity
      in late fasting increased in the 20-22 h period and concomitantly decreased in
      the two 4-6 h and 6-8 h periods. By contrast, VMH lesions markedly limited and
      delayed the rise in diurnal running activity, irrespective of the 2-hour period.
      They prevented any significant change in nocturnal activity pattern over the
      fast. In fasted sham-operated rats, the data may be interpreted as a phase
      advance of the nocturnal pattern of locomotor activity, concomitant with the
      increase of activity during daytime. These changes were suppressed by the VMH
      lesions. This suggests that the fasting-induced changes in the day-night pattern
      of locomotor activity are centrally mediated by a neuronal circuit involving the
      ventromedial hypothalamus.

PMID- 8762167
TI  - Effects of aspiration lesions of hippocampus or overlying neocortex on concurrent
      and configural object discriminations in rats.
AB  - Rats with aspiration lesions of the hippocampus plus overlying neocortex or
      control lesions of this cortex alone were trained on five-pair concurrent object
      discriminations in an enclosed Y-maze and subsequently on an open maze.
      Acquisition of the former task was impaired only in rats with cortical lesions,
      but on the latter both groups were equally impaired. Recombining positive and
      negative stimuli into novel pairs did not disrupt performance. Acquisition of
      single-pair discriminations was normal or slightly impaired in lesion groups. The
      cortical, but not the hippocampal group, was impaired on the concurrent learning
      of a positive and a negative pattern configural task. Recombining stimuli did not
      impair performance of this task either. The study demonstrates that extensive
      damage to the hippocampal formation need not necessarily impair concurrent
      learning, and impairments seen in other studies may relate to details of
      experimental procedure.

PMID- 8762168
TI  - Unilateral amygdala inactivation after training attenuates memory for reduced
      reward.
AB  - This experiment examined the effects of unilateral inactivation of the amygdalae
      on memory for reduction in reward magnitude. Male Sprague-Dawley rats with
      bilateral cannulae in the amygdala were trained to run a straight alley for ten
      45-mg food pellets. On Day 10, half the animals were shifted to a 1 pellet food
      reward and half continued to receive 10 pellets. After the shift, the shifted
      animals displayed a marked increase in response latencies. Immediately following
      training on Day 10, the animals received bilateral intra-amygdala infusions (0.5
      microliter/side) of phosphate buffer or 2% lidocaine in one amygdala
      simultaneously with infusion of buffer in the other amygdala. On Day 11, the
      shifted animals given bilateral buffer infusions displayed an increase in
      response latencies greater than that of the unshifted groups or the shifted
      groups given lidocaine unilaterally. On Day 12, the runaway latencies of the
      Shifted Vehicle group remained significantly higher than those of the Unshifted
      Vehicle group and the Shifted Unilateral Lidocaine-Right group but were not
      significantly different from those of the Shifted Unilateral Lidocaine-Left
      group. Also, the latencies of the Shifted Unilateral Lidocaine-Left group were
      significantly longer than those of the Shifted Unilateral Lidocaine-Right group.
      These findings indicate that post-shift inactivation of only one amygdala can
      attenuate the response to reward reduction. These results are consistent with
      previous evidence that the right amygdala may be more involved than the left in
      consolidation of memory storage for aversive experience.

PMID- 8762169
TI  - Behavioral studies on rats with transient cerebral ischemia induced by occlusion
      of the middle cerebral artery.
AB  - The behavioral effects of transient cerebral ischemia in adult Wistar rats were
      studied. In Experiment 1, rats were subjected to 90-min occlusion of the
      unilateral, left or right, middle cerebral artery (MCA) followed by
      recirculation. The locomotor activity had not changed 3 and 30 days after the
      occlusion, except that the number of rearing was significantly decreased by left
      MCA occlusion. Rats were examined in a radial maze system for learning and memory
      ability during 4 weeks from the 3rd day after ischemia (the 3rd day was counted
      as day 1 of the experiment). Maze performance was slightly disturbed due to focal
      brain damage by MCA occlusion, but the disturbance was statistically significant
      only on days 6, 11, and 15 in the right occlusion. In Experiment 2, rats were
      trained to master a radial maze task completely for 4 weeks, and then subjected
      to transient unilateral (right) ischemia as described above. These rats showed an
      increase in incorrect entry in the radial maze task from day 4 to day 14.
      However, on day 21, the number of incorrect entry decreased to the control level
      of the sham-operated group. The numbers of correct choice were inversely related
      with those of incorrect entry, though slightly blunted. Coincidentally, the time
      required to solve the maze task was also prolonged from day 4 to day 14, but
      returned to the control time on day 21. These results suggest that unilateral
      ischemia transiently suppresses both acquiring radial maze performance and
      maintenance of learned performance and that it is a good model for studying human
      focal cerebral ischemia.

PMID- 8762170
TI  - Unilateral frontal cortex ablation producing neglect causes time-dependent
      changes in striatal glutamate receptors.
AB  - This study's goal is to identify adaptations involving striatal glutamate (GLU)
      or dopamine (DA) receptors that may contribute to recovery of function following
      cortical injury. Unilateral aspiration of the medial agranular region of frontal
      cortex (AGm) in rats produces neglect of contralateral stimuli. Pharmacological
      and immunocytochemical studies suggest that glutamatergic and dopaminergic
      processes within striatum may contribute to spontaneous recovery from this
      neglect. This study examined by autoradiography radioligand binding to striatal
      GLU and DA receptor subfamilies in AGm-ablated rats surviving 5 days
      (unrecovered) or 3 or more weeks (recovered) postsurgery. Density of radioligand
      binding was quantified in striatal subregions by computerized image analysis.
      Compared to striatal binding densities in the intact hemisphere, [3H]kainate
      binding and [3H]GLU binding to NMDA receptors were decreased in the lesioned
      hemisphere of unrecovered AGm-ablated rats, but normalized (for kainate) or
      increased (for NMDA) in the lesioned hemisphere of recovered rats. Ablation of
      AGm did not affect [3H]AMPA binding or the binding of [3H]SCH23390,
      [3H]spiperone, or [3H]mazindol to dopaminergic D1 or D2 receptor subfamilies, or
      to DA uptake sites, respectively. The results suggest that a small percentage of
      NMDA and kainate receptors are located on corticostriatal axon terminals, and
      that over time an upregulation of striatal NMDA and/or kainate receptors may
      offset the loss of cortical glutamatergic input caused by cortical injury. These
      time-dependent alterations in GLU receptors may contribute to the recovery of
      function and normalizations of immediate early gene expression seen weeks after
      AGm ablation. Upregulation of striatal dopamine receptors was not evident, and
      thus is unlikely to mediate recovery from neglect produced by cortical injury.

PMID- 8762171
TI  - Kainic acid versus carbachol induced emotional-defensive response in the cat.
AB  - The emotional-defensive response (EDR) and accompanied neurotoxic and
      electroencephalographic (EEG) effects induced by injection of kainic acid (KA,
      0.1; 0.2 microgram) into the midbrain periaqueductal grey region (PAG) and antero
      medial hypothalamus (AMH) in the cat were examined and compared with EDR and
      accompanied neurotoxic and EEG effects induced by injection of cholinergic agent,
      carbachol (CCH), into the same sites. The injections of KA (0.2 microgram) into
      the PAG induced EDR which closely resembled the defense behavior typically
      observed after administration of CCH. However, in contrast to CCH-induced EDR,
      the defensive response induced by KA was found to be accompanied by EEG symptoms
      of epileptiform activity in the limbic cortex and a massive cell loss in the site
      of injection. It is proposed that KA-induced EDR and seizure activity may have
      resulted from the activation of different cell populations localized either in
      the vicinity of the injection (i.e., PAG region) and in the area remote from the
      injection loci, the limbic cortex. KA induced activation of PAG neuronal network
      would trigger the 'local response' (emotional-defensive response) and produce a
      remote effect-epileptiform activity.

PMID- 8762172
TI  - Intermale aggression and dark/light preference in ten inbred mouse strains.
AB  - The capacity of males to attack a passive standard opponent in a resident
      intruder test and the preferences in a dark/light choice situation were measured
      in 200 male mice from 10 different inbred mouse strains. Large strain differences
      were found for all variables recorded, i.e., the proportion of attacking males,
      the time spent in the brightly lit box, and the number of transitions between the
      lit and the dark boxes. A strong negative correlation was found between the first
      two variables. This result suggests that males of more attacking strains have a
      higher level of anxiety but do not differ for their level of activity. An
      involvement of GABA as mediating factor is suggested.

PMID- 8762173
TI  - Role of hippocampal 5-HT1A receptors on elevated plus maze exploration after a
      single restraint experience.
AB  - Previous studies have shown that 2 h restraint stress induces deficits in open
      arm exploration of an elevated plus maze 24 h later. This effect was attenuated
      by a post-stress systemic injection of the 5-HT non-selective agonist, 5-methoxy
      N,N-dimethyltryptamine (5-MeODMT). To verify a possible involvement of
      hippocampal 5-HT1A receptors in this effect, rats were stereotaxically implanted
      with canulae in the dorsal hippocampus. Seven days later they received bilateral
      microinjections of 5-MeODMT (20 nmol/0.5 microliter) or saline. No difference was
      found on exploration of an elevated plus maze 24 h later. However, when
      treatments were performed immediately after 2 h of restraint stress, the drug was
      able to increase open arm exploration 24 h later. This effect was antagonized by
      a previous microinjection of (+)WAY-100135 (40 nmol/0.5 microliter), a selective
      5-HT1A antagonist. The results suggest that hippocampal 5-HT1A receptors may
      attenuate stress behavioral consequences.

PMID- 8762174
TI  - Changes in striatal dopamine release in stress-induced conditioned suppression of
      motility in rats.
AB  - Rats received a footshock for 10 min in a chamber with a metallic grid floor, and
      then placed into the chamber for 30 min after 6 days. The motility of the shocked
      rats showed a significant decrease (conditioned suppression of motility). In
      addition, the extracellular dopamine (DA) levels in the striatum were also
      reduced significantly in in vivo microdialysis study. Thus, dysfunction in the
      striatal DAergic neuronal systems is responsible for mental stress responses such
      as conditioned fear stress.

PMID- 8762175
TI  - The GABAB receptor antagonist CGP 36,742 and the nootropic oxiracetam facilitate
      the formation of long-term memory.
AB  - The memory-enhancing effects of a single treatment with the GABAB antagonist CGP
      36,742 (10 mg/kg) or the nootropic agent oxiracetam (100 mg/kg) given immediately
      after a learning experience ('post-trial') remain detectable for at least 4
      months thereafter. This indicates that in all probability these substances
      facilitate the formation of the long-term memory trace.

PMID- 8762176
TI  - CGP 36,742, an orally active GABAB receptor antagonist, facilitates memory in a
      social recognition test in rats.
AB  - CGP 36,742, an orally active GABAB receptor antagonist, improves the retention
      performance of rats in a social recognition test. This effect is detectable over
      a very wide range of doses (0.03 to 300 mg/kg, p.o.). Considering its binding (32
      mumol affinity for the GABAB site) the surprisingly potent activity of CGP 36,742
      makes it appear quite possible that the effect is mediated by an as yet unknown
      receptor subtype.

PMID- 8762177
TI  - Phase-shifting effect of 8-OH-DPAT, a 5-HT1A/5-HT7 receptor agonist, on locomotor
      activity in golden hamster in constant darkness.
AB  - The present results show that under constant darkness the endogenous circadian
      pacemaker located in the suprachiasmatic nuclei can be affected by administration
      of 8-hydroxy-2-[di-n-propylamino] tetralin (8-OH-DPAT), a well known 5-HT1A/5-HT7
      receptor agonist. A single i.p. injection (0.1 ml) with 8-OH-DPAT (5 mg/kg)
      induced significant phase-advances of hamster locomotor activity at circadian
      time (CT) 6 and 8 and a significant phase-delay at CT11. Saline injections by
      themselves induced a significant phase-advance at CT10-11. The dose-response
      curve for 8-OH-DPAT showed a maximal phase-shifting effect for doses of at least
      2.5 mg/kg at CT8. Thus, in golden hamsters. (1) 8-OH-DPAT has a chronobiological
      effect with sensitivity depending upon the circadian time of injection, and (2) a
      single saline injection is able to induce regular phase-advances at the end of
      the subjective day (CT10-11).

PMID- 8762178
TI  - Reverberation of chloride-dependent synaptic potentials in the rat entorhinal
      cortex in vitro.
AB  - The spontaneous activity generated by rat entorhinal neurons during application
      of 4-aminopyridine (4AP; 50 microM) was studied with intracellular and
      extracellular field-potential recordings in an vitro slice preparation. Long
      lasting depolarizations (LLDs) with amplitudes of 15 +/- 7.6 mV (mean +/- SD; n =
      14) and durations of 1.65 +/- 0.77 s (n = 14) occurred at 0.036 +/- 0.01/s (n =
      14). Each LLD was followed by a rhythmic sequence of depolarizing potentials (up
      to 22 events) with amplitudes of 4-30 mV, durations of 40-500 ms and frequency of
      0.9 +/- 0.2/s (n = 14). These intracellular potentials were mirrored by negative
      going field potentials, suggesting that they represented synchronous events.
      Membrane input resistance decreased by 79-86% during both LLDs and subsequent
      rhythmic depolarizations. Intracellular injection of steady depolarizing or
      hyperpolarizing current modified the amplitude of these potentials in a similar
      manner: the reversal potential of the LLDs and of the rhythmic depolarizations
      was -66.4 +/- 4 mV and -67.9 +/- 3.2 mV, respectively (n = 7). Intracellular
      injection of Cl- increased the amplitude of both types of potentials. Spontaneous
      LLDs continued to occur during application of the non-N-methyl-D-aspartate (NMDA)
      receptor antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (10 microM), a
      procedure that abolished the subsequent rhythmic depolarizations (n = 3). LLDs
      were blocked by further addition of the gamma-aminobutyric acid (GABA)A receptor
      antagonist bicuculline methiodide (10 microM, n = 3). Our findings demonstrate
      that during 4AP application entorhinal neurons generate glutamatergic-independent
      LLDs as well as synchronous, Cl(-)-dependent depolarizations that reverberate
      through non-NMDA-mediated excitatory circuits.

PMID- 8762179
TI  - Glutamate is transported across the rat blood-brain barrier by a sodium
      independent system.
AB  - Transport of L-glutamate from blood to brain in equithesin-anesthetized rats was
      examined using in situ brain perfusion combined with multiple-time/graphical
      analysis. In situ perfusion allowed precise control of the composition of the
      perfusate, which was necessary for a detailed investigation of glutamate
      transport, while multiple time/graphical analysis permitted evaluation of the
      rapidly reversible volume and the period when the influx was unidirectional.
      Glutamate had no reversible volume and efflux from brain occurred after 30 s of
      perfusion. The in situ transfer coefficient (Kin) ranged from 0.74 +/- 0.07 mul/s
      per g in parietal cortex to 0.44 +/- 0.07 mul/s per g in hippocampus. L-Glutamate
      uptake was unaffected by removal of sodium from the perfusate, reduced by 5 mM L
      glutamate, L-homocysteate, L-aspartate, plasma and 0.1 mM L-glutamate, while L
      cystine did not reduce its uptake. These results suggest that the transport
      system for glutamate is saturated mainly by L-glutamate at physiological
      conditions and that it is not the sodium-independent x-C system since glutamate
      transport was not reduced by L-cystine except in hippocampus and that it was
      responsive to L-aspartate.

PMID- 8762180
TI  - Increased beta-amyloid precursor protein mRNA in the rat cerebral cortex and
      hippocampus after chronic systemic atropine treatment.
AB  - Rats were treated with once-daily subcutaneous injections of atropine or normal
      saline for 10 days. Cryostat sections of fresh-frozen brain were subjected to
      quantitative muscarinic receptor ([3H]quinuclidinylbenzilate (QNB)) binding
      autoradiography, and quantitative in-situ hybridization autoradiography for beta
      amyloid precursor protein (beta-APP) mRNA using an oligonucleotide probe
      recognizing all major isoforms. QNB binding in the atropine-treated group was
      increased 6-7% in the areas measured (dentate gyrus, CA1, and cerebral cortex),
      confirming that the treatment was effective in inducing muscarinic receptor
      upregulation. Hybridization signal for beta-APP mRNA was increased 15-20% in the
      atropine-treated group in the same regions. As chronic atropine treatment models
      the muscarinic effects of cholinergic denervation, these results suggest that age
      related cholinergic neuron loss may result in upregulation of beta-APP.

PMID- 8762181
TI  - Mouse G2-GPI AChE is processed as a membrane-bound ectoenzyme in transfected
      mouse sarcoma cells but is not a homophilic adhesion molecule.
AB  - Acetylcholinesterase (AChE) is mainly involved in synaptic transmission by
      hydrolyzing acetylcholine in the synaptic cleft. It has been suggested that it
      could also be involved in other functions such as cell-cell adhesion. In this
      study, we have expressed mouse G2-GPI AChE at the membrane surface of S180 cells.
      We obtained a transfected cell line which permanently expresses high levels of
      AChE at the cell surface. However, transfected cells behave as single cells in
      culture. We performed cell aggregation and adhesion tests and found no
      significant aggregation or adhesion, which suggests that AChE is not a homophilic
      adhesion molecule.

PMID- 8762182
TI  - Detection of neuron-specific protein gene product (PGP) 9.5 in the rat and
      zebrafish using anti-human PGP9.5 antibodies.
AB  - Protein gene product (PGP) 9.5 is a developmentally regulated neuron- and
      neuroendocrine cell-specific ubiquitin carboxy-terminal hydrolase (UCHL1)
      expressed throughout the mammalian central and peripheral nervous systems. We
      have compared the use of monoclonal and polyclonal antibodies raised against
      human PGP9.5 for immunodetection of the protein in tissues of the zebrafish and
      rat. We show that a monoclonal antibody 13C4, which recognises an N-terminal
      epitope, detects PGP9.5 on Western blots as a single 27 kDa band present at high
      levels in zebrafish and rat brain. By contrast, the polyclonal antisera
      recognises multiple tissue-specific proteins in the rat and fails to detect
      PGP9.5 in the zebrafish. Finally, we have developed a specific ELISA assay for
      detection of cellular PGP9.5 using MAb13C4 and have employed the assay to show
      that PGP9.5 is not upregulated during nerve growth factor (NGF)-induced
      differentiation of rat PC12 cells.

PMID- 8762183
TI  - Changes in intracellular calcium induced by NMDA in cultured rat hippocampal
      neurons require exogenous glycine.
AB  - Confocal laser scanning microscopy was used to study changes in intracellular
      free calcium concentration ([Ca2+]i) at the level of the soma of cultured
      hippocampal neurones following pressure application of glutamate or N-methyl-D
      aspartate (NMDA). [Ca2+]i was imaged in the presence of tetrodotoxin after
      loading cells with the fluorescent dye indicator fluo-3/AM. Responses to
      glutamate were potently antagonized by 6-cyano-7 nitroquinoxaline-2,3-dione
      (CNQX: 20 microM). They were also strongly and reversibly depressed by 3-((+/-)-2
      carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP; 20 microM), leaving a
      small CNQX-sensitive component. Responses to NMDA were also blocked by CNQX. In
      the presence of saturating concentrations of glycine (100 microM), the depression
      of glutamate or NMDA responses by CNQX was greatly reduced. Exogenously applied
      glycine also potentiated the NMDA response. These data indicate that the glycine
      binding site of the NMDA receptor channel is not saturated in cultured
      hippocampal neurones and thus is susceptible to the action of agonists or
      antagonists.

PMID- 8762184
TI  - Determination on functional basis of presynaptic alpha 2-adrenoceptor subtypes in
      guinea-pig duodenum.
AB  - The effects of several alpha 2-adrenoceptor agonists and antagonists were
      examined on the cholinergic twitch contractions evoked by electrical field
      stimulation of guinea-pig duodenum. Oxymetazoline, xylazine, noradrenaline, alpha
      methyl-noradrenaline or medetomidine (0.01-30 microM) were nearly equieffective
      in inhibiting duodenal twitch responses. The effects of xylazine were
      competitively counteracted by antagonists tested (0.03-10 microM) with the
      following order of potency: RX 821002 = idazoxan > rauwolscine = yohimbine = BRL
      44408 >> prazosin = ARC 239 = BRL 41992. According to the current classification,
      it is suggested that alpha 2-heteroadrenoceptors involved in the modulation of
      duodenal cholinergic neurotransmission belong to the alpha ZD subtype.

PMID- 8762185
TI  - Characterization of the regulatory regions of murine alpha 2C2 adrenoceptor
      subtype gene.
AB  - In order to delineate the regulatory mechanisms underlying the control of alpha 2
      adrenoceptor expression, the sequence of 5' (1145 bp) and 3' (2682 bp) flanking
      regions of murine alpha 2C2 subtype gene were determined and characterized from a
      genomic phage clone MA2C2. The 5' flanking region has no TATA box yet with high
      GC content. The 3' flanking region is marked by the presence of a polyadenylation
      signal 2.3 kb down stream from the stop codon. The transcription start site was
      mapped by 5' rapid amplification of cDNA ends (RACE) and primer extension assays
      at nucleotide A, 415 bp upstream from the first initiation codon and resides in a
      motif resembling the consensus sequence of initiator found in many TATA-less
      promoters. An NcoI fragment (4.7 kb) immediately upstream from the translation
      initiation site was linked to a reporter gene lacZ. Using an in vitro
      transfection assay, cell lines of renal or neural origin were identified as
      permissive hosts for alpha 2C2 subtype expression. With its core promoter clearly
      defined and sequence of the regulatory regions at hand, this in vitro gene
      transfer system will facilitate the identification of putative cis-elements and
      transcription factors key to alpha 2C2 adrenoceptor expression.

PMID- 8762186
TI  - EM colocalization of AMPA and NMDA receptor subunits at synapses in rat cerebral
      cortex.
AB  - Electrophysiology and light microscopy suggest that a single excitatory synapse
      may use both amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and N-methyl-D
      aspartate (NMDA) receptors. Using immunogold electron microscopy, we here provide
      direct evidence for colocalization at individual synapses in sensorimotor cortex
      of adult rats. Colocalization was most commonly observed on dendritic spines;
      subunits of the two classes of receptors seemed to be independently distributed
      within the synaptic active zone.

PMID- 8762187
TI  - Development of low magnesium-induced spontaneous synchronized bursting and
      GABAergic modulation in cultured rat neocortical neurons.
AB  - Development of spontaneous synchronized bursting in the early stages of rat
      neocortical neuronal cultures was studied by whole-cell and extracellular
      recordings. Neocortical neurons from rat embryos were cultured on planar
      electrode arrays, and low Mg(2+)-induced spontaneous activity was recorded from 5
      to 16 days in vitro (DIV). At 5-6 DIV the current synchronized to the bursting
      had only a slow component lasting 3-5 s, whereas in older cultures a fast
      transient component was dominant. A gamma-aminobutyric acid (GABA)A receptor
      antagonist, bicuculline methiodide, had little effect on the spontaneous activity
      at 5-6 DIV, whereas in older cultures it had a marked effect on the slow current
      component. These results suggest a role of GABAergic transmission in the
      development of synchronized activities.

PMID- 8762188
TI  - Direct and indirect activation of human corticospinal neurons by transcranial
      magnetic and electrical stimulation.
AB  - Corticospinal volleys and surface electromyographic (EMG) responses evoked by
      magnetic and electrical transcranial stimulation were recorded simultaneously in
      three conscious human subjects. For magnetic stimulation, the figure-of-eight
      coil was held on the hand motor area either with the induced current through the
      brain flowing in a postero-anterior direction (P-A stimulation) or in a latero
      medial direction (L-M stimulation). For electrical stimulation, the anode was
      placed 7 cm lateral to the vertex and cathode at the vertex (anodal stimulation).
      The P-A stimulation that was generally used preferentially evoked I waves,
      whereas the L-M and anodal stimulation preferentially evoked D wave. The results
      suggested that the mode of activation by transcranial magnetic stimulation
      altered, depending on its current direction, and the difference between P-M
      magnetic and electrical stimulation can be explained by the context of the D and
      I hypothesis.

PMID- 8762189
TI  - GABAergic synapses upon neurons expressing substance P receptors in the nucleus
      of the solitary tract: an immunocytochemical electron microscope study in the
      rat.
AB  - Morphological substrates for interactions between gamma-aminobutyric acid (GABA)
      and substance P upon neurons expressing substance P receptor (SPR) in the nucleus
      of the solitary tract (NST) were investigated by immunocytochemical electron
      microscopy. In the NST of the rat, many GABA-like immunoreactive axon terminals
      were in symmetric synaptic contacts with dendritic profiles; they were observed
      on nearly a half of the SPR-like immunoreactive dendritic profiles in the medial
      part of the caudal half of the NST.

PMID- 8762190
TI  - Single electrical shock of a somatic afferent nerve elicits A- and C-reflex
      discharges in gastric vagal efferent nerves in anesthetized rats.
AB  - The possibility that single electrical shock stimulation of somatic afferent
      nerves could evoke a reflex response in vagal efferent nerves innervating the
      stomach was examined using anesthetized, artificially-ventilated rats. A single
      shock to a hindlimb afferent nerve (tibial nerve) produced two distinct reflex
      components in gastric vagal efferent nerves; namely (1) A-reflex discharges with
      a latency of about 120 ms and a duration of about 200 ms elicited by stimulation
      of myelinated A afferent fibers, and (2) C-reflex discharges with a latency of
      about 360 ms and a duration of about 200 ms elicited by stimulation of
      unmyelinated C afferent fibers. A single shock to a first lumbar spinal afferent
      nerve produced only a week reflex component with a latency of about 120 ms and a
      duration of about 190 ms in gastric vagal efferent nerves. Limb afferents appear
      to have stronger central pathways functionally connecting to gastric vagal
      efferent preganglionic neurons in the brainstem, than do abdominal afferents.

PMID- 8762191
TI  - Role of spleen or spleen products in the reduced locomotor-enhancing effect of
      morphine in diabetic mice.
AB  - In the present study, we examined the possibility that factor(s) derived from
      spleen cells are involved in the reduced morphine-induced hyperlocomotion in
      diabetic mice. The mean total locomotor activity after s.c. administration of
      morphine (20 mg/kg) in non-diabetic mice was significantly greater than that in
      diabetic mice. Splenectomized diabetic mice had a significantly higher
      sensitivity to morphine-induced hyperlocomotion than untreated or sham-operated
      diabetic mice. However, morphine-induced hyperlocomotion in non-diabetic mice was
      unaffected by splenectomy or sham-operation. Furthermore, 7 days after adoptive
      transfer of the supernatant of spleen cell homogenate (SSCH) from diabetic mice
      (SSCH-D), naive mice that had been injected with SSCH-D showed lower morphine
      induced locomotor activity than mice which had been injected with SSCH from non
      diabetic mice (SSCH-ND). These results suggest that some factor(s) derived from
      spleen cells may play an important direct or indirect role in the selective
      reduction of morphine's locomotor-enhancing effect in diabetic mice.

PMID- 8762192
TI  - Apolipoprotein E is highly susceptible to oxidation by myeloperoxidase, an enzyme
      present in the brain.
AB  - Apolipoprotein E, the most common apolipoprotein found in the brain, is linked to
      several pathologies like Alzheimer's disease. Apolipoprotein E directly binds to
      beta-amyloid with a strong affinity. Myeloperoxidase, a protein secreted by
      neutrophils and involved in the inflammatory process, is also present in the
      brain. In vitro myeloperoxidase oxidation of recombinant human apolipoprotein E
      leads to fragmentation of the protein with low concentrations of hydrogen
      peroxide and polymerization with higher concentrations. Comparison with bovine
      serum albumin shows a higher susceptibility of apolipoprotein E to
      myeloperoxidase oxidation, which may have importance in the Alzheimer's disease
      process.

PMID- 8762193
TI  - Expression of apolipoprotein E inhibits aggregation of the C-terminal fragments
      of beta-amyloid precursor protein.
AB  - An important role of apolipoprotein E in the amyloidogenesis of Alzheimer's
      disease is suggested by an accumulation of apolipoprotein E in beta-amyloid
      plaques and a genetic association between Alzheimer's disease and one of the
      allelic variants (APOE4) of apolipoprotein E. Overexpression of a C-terminal
      region of beta-amyloid precursor protein brings about aggregation of the C
      terminal fragments in COS cells. This COS cell culture system was used to study
      effects of apolipoprotein E on aggregation of the C-terminal fragments. When both
      apolipoprotein E and the C-terminal fragments were overexpressed in COS cells,
      Western blot analyses revealed significant inhibition of aggregation of the C
      terminal fragments. No significant differences between apolipoprotein E3 and E4
      in the inhibitory activities were found by this method. Apolipoprotein E may
      inhibit formation of amyloid fibrils.

PMID- 8762194
TI  - Mutation of low affinity nerve growth factor receptor gene is associated with the
      hypertensive phenotype in spontaneously hypertensive inbred rat strains.
AB  - We previously reported a missense mutation in the low affinity nerve growth
      factor receptor (LNGFR) gene of spontaneously hypertensive rats (SHR), proposing
      this gene as a promising candidate in genetic hypertension. In this study we
      provide further support for implicating this gene in genetic hypertension using
      two new inbred strains, WKHT and WKHA rats. These strains originated from
      crossbreeding SHR rats with normotensive Wistar-Kyoto rats (WKY): WKHT rats are
      hypertensive but not hyperactive, and WKHA rats are hyperactive but not
      hypertensive. Nucleotide sequence analysis of the LNGFR gene revealed that WKHT
      has the same mutation as SHR, whereas WKHA has the normal sequence, as seen in
      WKY. These results support our original hypothesis that the mutated LNGFR gene is
      linked to hypertension, since the mutation had co-segregated with the
      hypertensive trait, and not hyperactivity trait of SHR.

PMID- 8762195
TI  - The benefits of lowering elevated blood pressure: a critical review of studies of
      cardiovascular morbidity and mortality in hypertension.

PMID- 8762196
TI  - Structural changes of large conduit arteries in hypertension.
AB  - BACKGROUND: Structural alterations of large conduit arteries are a common pathway
      for any complication of hypertensive vascular disease. Whether increased arterial
      wall thickness occurs at an early phase in uncomplicated hypertension has
      remained largely ignored until recent years. METHODS: Sophisticated echo-Doppler
      techniques with a high degree of resolution and reproducibility have been
      developed to obtain reliable non-invasive determinations of intima-media
      thickness of superficial arteries such as the radial and the common carotid
      arteries. RESULTS: In uncomplicated hypertension, a significant increase in
      intima-media thickness is observed at the sites both of the radial and of the
      carotid arteries. The former is known to be constantly undamaged by
      atheroscierosis and is composed almost exclusively of arterial smooth muscle;
      operational arterial stiffness is found to be normal. The latter is strongly
      affected by atheroscierosis and predominantly composed of elastin and collagen
      fibres; operational arterial stiffness is found to be increased. In old subjects
      with systolic hypertension, radial artery hypertrophy is significantly reversed
      by drug therapy involving diuretics, converting enzyme inhibitors or both. This
      change occurs in parallel with the reduction in blood pressure. CONCLUSION: In
      sustained essential hypertension, arterial wall hypertrophy can be demonstrated
      in the absence of organ damage. Operational arterial elasticity is maintained in
      peripheral but not in central arteries. Structural changes of the large conduit
      arteries are substantially reversed by drug therapy together with a reduction in
      blood pressure.

PMID- 8762197
TI  - Prediction of the actual awake and asleep blood pressures by various methods of
      24 h pressure analysis.
AB  - OBJECTIVE: To assess the relationships of daytime and night-time blood pressures
      and the day-night pressure differences, obtained by various analytical methods,
      with the actual awake and asleep pressures and the awake-asleep pressure
      difference. METHODS: Ambulatory blood pressure was successfully monitored by use
      of the SpaceLabs 90202 device in 91 healthy young men during a weekend, when they
      went to bed and awoke at variable and often unusual times. The actual 'awake' and
      'asleep' blood pressures were calculated on the basis of these times, noted by
      the subjects. The 24 h recordings were further analysed by use of two clock time
      independent methods (square-wave fitting; cumulative sum analysis) and by one
      'wide' (A) and one 'narrow' (B) fixed-time method (daytime: 0700-2200 h or 1000
      2000 h; night-time: 2200-0700 h or 0000-0600 h, for methods A and B,
      respectively). RESULTS: In the total study population, square-wave fitting (+1.1
      +/- 1.5 mmHg, mean +/- SD) and cumulative sum analysis (2.4 +/- 1.9 mmHg)
      overestimated the actual awake systolic blood pressure and underestimated the
      asleep pressure (-0.7 +/- 1.7 and -1.8 +/- 1.8 mmHg, respectively). The fixed
      time techniques underestimated the awake pressure (-2.6 +/- 3.1 and -0.2 +/- 3.2
      mmHg for methods A and B, respectively) and overestimated the asleep pressure by
      +4.9 +/- 5.5 and +2.7 +/- 6.1 mmHg, respectively. The actual awake-asleep
      pressure difference was overestimated by square-wave fitting (+1.8 +/- 1.9 mmHg)
      and more so by cumulative sum analysis (+4.2 +/- 2.5 mmHg); the underestimation
      by the fixed time approach averaged -3.0 +/- 8.4 mmHg with method B and amounted
      to -7.5 +/- 8.3 mmHg with method A. Overall, the SD of the various differences
      between the estimated and the actual awake and asleep pressures, and consequently
      the limits of agreement, were larger for the fixed-time methods than for the
      clock time-independent techniques. In the 47 subjects who went to bed before 2400
      h and awoke between 0600 and 1000 h, the results of the clock time-independent
      methods were similar to the results in the total study population, whereas the
      deviations of the fixed time pressures from the actual awake and asleep blood
      pressures were considerably reduced. The results were similar for diastolic blood
      pressure. CONCLUSIONS: Clock time-independent methods, particularly square-wave
      fitting, can predict the actual awake and asleep blood pressures and the awake
      asleep pressure differences with reasonable accuracy and the results are
      independent of the awake-asleep pattern of the subjects. However, fixed-time
      methods are only reliable when the subjects go to bed and arise within well
      defined periods, and yield more accurate results when the morning and evening
      phases are excluded from the daytime and night-time periods.

PMID- 8762198
TI  - Does it matter whether ambulatory blood pressure is recorded during a work day or
      a non-work day?
AB  - OBJECTIVE: To compare ambulatory blood pressure recorded during a work day with
      that recorded during a non-work day. DESIGN: A cross-over randomized study in
      middle-aged treated hypertensives and normotensives. SETTING: Primary health
      care. SUBJECTS: Forty treated hypertensives (20 men) and 40 normotensives (20
      men). MAIN OUTCOME MEASURE: Individual difference between ambulatory blood
      pressures recorded during a work day and during a non-work day. RESULTS: The
      systolic/diastolic blood pressure of the hypertensives was 2/3 (7/5) [mean (SD)]
      mmHg higher and that of the normotensives 3/3 (5/4) mmHg higher during the work
      day 24 h monitoring. The blood pressure of the normotensives showed a
      statistically significant difference between the two monitoring periods both for
      systolic and for diastolic blood pressure during 24 h and daytime. The
      corresponding comparison in the hypertensives showed a significant difference
      only for diastolic blood pressure. During night-time there was no statistically
      significant difference between the two monitoring periods, neither in the
      hypertensives nor in the normotensives. Individual comparisons revealed large
      variations between the two monitoring periods in many subjects. Among the
      hypertensives the percentage of subjects with a systolic blood pressure
      difference > 10 mmHg (higher or lower during their work day monitoring period)
      was 20% during 24 h, 32.5% during daytime and 15% during night-time. The
      corresponding values for a diastolic blood pressure difference > 5 mmHg were 40%
      during 24 h, 32.5% during daytime and 40% during night-time. Among the
      normotensives the corresponding values for systolic/diastolic blood pressure
      differences between the two monitoring periods were 5/27.5% during 24 h, 5/27.5%
      during daytime and 2.5/27.5% during night-time. CONCLUSION: Ambulatory blood
      pressure recorded during a work day might differ from that recorded during a non
      work day. It is important to be aware of this fact when evaluating individual
      blood pressure graphs, although the importance of this for the development of
      organ damage is not known. To perform more than a single 24 h blood pressure
      monitoring can be of value to obtain a better idea of the blood pressure
      variability of a patient.

PMID- 8762199
TI  - Association of angiotensin converting enzyme activity and arterial blood pressure
      in a population-based sample.
AB  - OBJECTIVE: To investigate the relationship between circulating angiotensin
      converting enzyme activity and arterial blood pressure in a population-based
      sample of 646 middle-aged subjects. RESULTS: After exclusion of subjects taking
      antihypertensive medication and those with electrocardiographic evidence of
      myocardial infarction, univariate analyses revealed that systolic blood pressure
      was significantly correlated with age and with body mass index. Also, angiotensin
      converting enzyme activity in men (n = 230) was found to be related both to
      systolic and to diastolic blood pressure. Inclusion of all of the men slightly
      strengthened the association between angiotensin converting enzyme activity and
      systolic or diastolic blood pressure. Multilinear regression models that included
      age, body mass index and antihypertensive therapy as obligatory covariates
      confirmed an independent correlation between angiotensin converting enzyme
      activity and systolic or diastolic blood pressure in the men. Furthermore,
      untreated men from the highest quartile of angiotensin converting enzyme activity
      displayed significantly higher mean systolic and diastolic blood pressure values
      than did those from lower quartiles, even after adjustment for covariates. In
      contrast, untreated women (n = 264) displayed no evidence for such associations
      between angiotensin converting enzyme activity and blood pressure. CONCLUSION:
      The data suggest that the variability of serum angiotensin converting enzyme
      activity occurring in this large population-based sample might be related to the
      level of arterial blood pressure levels in men.

PMID- 8762200
TI  - Attenuated endothelium-dependent vascular relaxation in patients with sleep
      apnoea.
AB  - OBJECTIVE: To evaluate endothelium-dependent vascular function in obstructive
      sleep apnoea patients. DESIGN AND METHODS: Forearm blood flow and vascular
      resistance were studied in eight normotensives and eight obstructive sleep apnoea
      patients and also in eight normotensive and eight hypertensive controls after
      graded brachial artery infusion of acetylcholine (10-60 micrograms/min) and
      sodium nitroprusside (1-6 micrograms/min), respectively. Patients and controls
      were matched for age, sex and body weight. RESULTS: Forearm blood flow after
      acetylcholine infusion was reduced in patients compared with that in controls
      (peak flows were 6.0 +/- 0.7 and 9.8 +/- 1.5 ml/min for 100 g, respectively), but
      there was no difference between hypertensive and normotensive subjects. However,
      the hypertensive obstructive sleep apnoea group exhibited a reduced flow response
      to sodium nitroprusside compared with that of their corresponding hypertensive
      controls. Minimal forearm vascular resistance after acetylcholine infusion and
      after sodium nitroprusside infusion was higher in obstructive sleep apnoea
      patients than it was in controls. CONCLUSIONS: Endothelium-dependent vascular
      relaxation in patients with obstructive sleep apnoea was reduced independently of
      hypertension. An additional defect in endothelium-independent vascular relaxation
      was found in obstructive sleep apnoea patients with hypertension. These findings
      suggest a vascular pathogenetic link between obstructive sleep apnoea and
      systemic hypertension.

PMID- 8762201
TI  - Regulation of secretion and clearance of C-type natriuretic peptide in the
      interaction of vascular endothelial cells and smooth muscle cells.
AB  - OBJECTIVE: To clarify the significance of C-type natriuretic peptide in the
      interaction between endothelial cells and vascular smooth muscle cells by
      investigating the endothelial production of C-type natriuretic peptide and the
      clearance mechanism of C-type natriuretic peptide using the endothelial cells
      smooth muscle cells co-culture system. RESULTS: Secretion of C-type natriuretic
      peptide in the direct co-culture of endothelial cells with smooth muscle cells
      elicited as much as a 60-fold increase compared with endothelial cells alone. The
      accumulation of intracellular cyclic GMP in the co-culture was consequently
      increased and the elevation of cyclic GMP level in the co-culture was abolished
      by the anti-C-type natriuretic peptide monoclonal antibody. The elevated cyclic
      GMP production in the co-culture was abolished by the anti-transforming growth
      factor-beta neutralizing antibody. Candoxatrilat (10(-6)-10(-4) mol/l), a neutral
      endopeptidase inhibitor, dose-dependently increased the concentrations of C-type
      natriuretic peptide in the culture medium with endothelial cells alone, but not
      in the endothelial cells-smooth muscle cells co-culture. The transcript of
      neutral endopeptidase messenger RNA was detected in endothelial cells but not in
      smooth muscle cells by reverse transcriptase polymerase chain reaction. Treatment
      with C-atrial natriuretic factor4-23 (10(-9)-10(-6) mol/l), the specific ligand
      for the clearance receptor of the natriuretic peptides, resulted in dose
      dependent augmentation of C-type natriuretic peptide concentration and
      concomitant intracellular cyclic GMP production in the endothelial cells-smooth
      muscle cells co-culture but not in endothelial cells alone. CONCLUSION: The
      present study demonstrated that direct interaction between endothelial cells and
      smooth muscle cells augments C-type natriuretic peptide secretion from
      endothelial cells through transforming growth factor-beta activation, and
      revealed that the enzymatic degradation is responsible for the steady state level
      of C-type natriuretic peptide in endothelial cells alone and that the receptor
      mediated clearance mainly determines the augmented level of C-type natriuretic
      peptide in the interaction between endothelial cells and smooth muscle cells. The
      results taken together raise the possibility that endothelial C-type natriuretic
      peptide might play a role in regulation of vascular tone and remodelling.

PMID- 8762202
TI  - Inhibition by cyclic AMP of basal and induced inositol phosphate production in
      cultured aortic smooth muscle cells from Wistar-Kyoto and spontaneously
      hypertensive rats.
AB  - OBJECTIVE: To investigate inositol phosphate formation and its modulation by the
      cyclic AMP (cAMP) pathway in cultured aortic smooth muscle cells from
      spontaneously hypertensive rats (SHR). METHODS: Phenylephrine was used to
      stimulate inositol phosphate formation in cultured aortic smooth muscle cells
      from SHR and Wistar-Kyoto (WKY) rats. The smooth muscle cells from passages 6-14
      were prelabelled with myo-[2-3H]-inositol (1.9 x 10(5) Bq/ml for 24 h) and
      inositol phosphate formation was measured after exposure to agonist for 45 min. (
      )isoproterenol or forskolin-induced cAMP formation was also evaluated using a
      radioimmunoassay method. RESULTS: The basal level of inositol phosphate formation
      in smooth muscle cells from SHR was higher than that observed in smooth muscle
      cells from WKY rats. Phenylephrine increased the formation of inositol phosphates
      in a concentration-dependent manner (0.1-100 mumol/l). In the presence of 100
      mumol/l phenylephrine, the increase in inositol phosphate formation was
      significantly greater in smooth muscle cells from SHR (214 +/- 6%) than that
      observed in smooth muscle cells from WKY rats (156 +/- 8%). When the cells were
      pretreated with 1 mmol/l 8-bromoadenosine 3':5'-cyclic monophosphate or with 10
      mumol/l forskolin for 45 min, the basal production of inositol phosphates in
      smooth muscle cells both from SHR and from WKY rats was significantly and
      similarly decreased by about 20%. In the presence of 1 mmol/l 8-bromoadenosine
      3':5'-cyclic monophosphate, 100 mumol/l phenylephrine-induced inositol phosphate
      formation was similarly decreased by 33 +/- 4 and 30 +/- 3% in smooth muscle
      cells from SHR and from WKY rats, respectively, whereas, in the presence of 10
      mumol/l forskolin, inositol phosphate formation was reduced by 25 +/- 3 and 27 +/
      5%, respectively, in those cells. In contrast, isoproterenol induced less
      inhibition of phenylephrine-induced inositol phosphate formation in smooth muscle
      cells from SHR (14 +/- 2%) than it did in those from WKY rats (25 +/- 4.5%).
      Although there was no significant difference in basal or forskolin-induced cAMP
      accumulation between smooth muscle cells from SHR and those from WKY rats. (
      )isoproterenol-induced cAMP accumulation was significantly lower in smooth muscle
      cells from SHR. CONCLUSION: A marked inhibitory effect of cAMP on the alpha 1
      adrenoceptor-mediated inositol phosphate signal transduction pathway was
      demonstrated in smooth muscle cells of SHR and of WKY rats. Decreased cAMP
      formation with beta-adrenergic stimulation and increased inositol phosphate
      formation with alpha-adrenergic stimulation in SHR smooth muscle cells may both
      contribute to the dominant alpha 1-adrenergic activity observed in SHR.

PMID- 8762203
TI  - Kinins or nitric oxide, or both, are involved in the antitrophic effects of
      angiotensin converting enzyme inhibitors on diabetes-associated mesenteric
      vascular hypertrophy in the rat.
AB  - OBJECTIVE: To determine the roles played by kinins/nitric oxide and angiotensin
      II in the antitrophic effects of angiotensin converting enzyme inhibitors on
      mesenteric arteries after 3 weeks of streptozotocin diabetes by using blockers
      both of the angiotensin II AT1 receptor and of the bradykinin B2 receptor.
      DESIGN: Male diabetic Wistar rats were randomly allocated to receive no
      treatment, the angiotensin converting enzyme inhibitors perindopril or ramipril,
      the AT1 receptor blocker ZD7155, the bradykinin B2 receptor blocker Hoe 140, the
      nitric oxide synthase inhibitor NG-nitro-L-arginine-methyl ester, concomitant
      administration of perindopril plus subcutaneous Hoe 140, perindopril plus NG
      nitro-L-arginine, or ramipril plus Hoe 140 (Hoe 140 administered via an Alzet
      mini-osmotic pump). METHODS: After 3 weeks, the rats were killed, their blood
      collected and their mesenteric vessels removed. The mesenteric vascular weight
      was measured and the media wall: lumen area ratio was assessed using quantitative
      histomorphometric techniques. RESULTS: Diabetes was associated with an increase
      in mesenteric weight and media wall:lumen area ratio. The angiotensin converting
      enzyme inhibitors, perindopril and ramipril, and the AT1 receptor antagonist
      ZD7155 reduced blood pressure and attenuated vascular weight and media wall:lumen
      area ratio. Concomitant administration of an angiotensin converting enzyme
      inhibitor with the kinin antagonist Hoe 140, administered either subcutaneously
      or via a mini-osmotic pump, or of the nitric oxide synthase inhibitor NG-nitro-L
      arginine attenuated the effect of the angiotensin converting enzyme inhibitor on
      the mesenteric vascular weight and wall:lumen area ratios. Treatment with Hoe 140
      or NG-nitro-L-arginine alone affected none of these parameters. CONCLUSION: The
      antitrophic effect of angiotensin converting enzyme inhibitors on diabetic
      mesenteric arteries is mediated by inhibition of angiotensin II and by actions on
      the kinin-nitric oxide pathway.

PMID- 8762204
TI  - The effect of chronic hypertension on skin blood flow.
AB  - OBJECTIVE: To determine whether the cutaneous microvasculature of the
      spontaneously hypertensive rat (SHR) is affected by chronic hypertension. DESIGN:
      We used laser Doppler techniques to measure skin blood flow in 22 SHR and in 22
      non-hypertensive Wistar-Kyoto (WKY) rats over a 1-year time span, beginning at
      age 3 months. Sites of measurement included the back, leg, and root of the tail,
      areas with a predominantly nutritive perfusion, and the plantar surface of the
      paw, which has a large contribution from large arterioles and venules. Flow was
      measured at basal skin temperature and at the maximally heat-stimulated condition
      of 44 degrees C. Systolic tail arterial blood pressures were measured
      concurrently. RESULTS: At baseline, systolic blood pressures were considerably
      higher in the SHR (190 +/- 4 mmHg) than they were in the WKY rats (138 +/- 2
      mmHg). Skin blood flow values at the three nutritive sites were similar in the
      two species. However, at 44 degrees C, flow was significantly higher at the paw
      in the SHR (46.8 +/- 3.5 versus 34.3 +/- 2.2 ml/min per 100 g). We attribute this
      difference to the effect of high perfusion pressure on large arterioles. During
      the 1-year measurement period, there was no appreciable change in blood flow in
      the WKY rats. In contrast, the SHR showed a steady progressive decline in skin
      blood flow at all sites. The largest decline was at the paw with a rate of fall
      of about 2.4%/month. After 1 year, there was no difference between paw blood flow
      in the SHR (27.5 +/- 1.8 ml/min per 100 g) and in the WKY rats (27.6 +/- 1.9
      ml/min per 100 g). CONCLUSIONS: Skin blood flow reserve falls in response to
      chronic hypertension. The rate of fall is greater at sites with significant
      arteriovenous perfusion that at nutritive sites.

PMID- 8762205
TI  - Sulfhydryl groups of renal D1A dopamine receptors: differential sensitivity of
      receptors to N-ethylmaleimide in normotensive and hypertensive rats.
AB  - OBJECTIVES: To determine whether sulfhydryl groups are present on D1A receptors
      of spontaneously hypertensive rats (SHR) and to test the hypothesis that failure
      of agonists to bind to such receptors is linked to microstructural changes
      involving sulfhydryl groups. METHOD: Alkylation of renal proximal tubule
      membranes by N-ethylmaleimide caused 70% loss of D1A dopamine receptor binding
      sites in the normotensive Wistar-Kyoto (WKY) rat and the SHR. RESULTS: The
      concentration of N-ethylmaleimide (IC50) required to produce half-maximal loss of
      receptor binding was 5.2 and 1200 mumol/l in WKY rats and SHR, respectively.
      Previous receptor occupancy of WKY rat D1A sites by the D1A agonist SKF R-38393
      completely protected the binding sites from N-ethylmaleimide-mediated
      inactivation. Occupancy with the D1A antagonist SCH 23390 partially protected the
      binding sites and produced a 500-fold increase in the IC50 of N-ethylmaleimide.
      In SHR, receptor occupancy either by SKF R-38393 or by SCH 23390 failed to
      protect the D1A sites from N-ethylmaleimide or to alter the IC50 of N
      ethylmaleimide-mediated inactivation. CONCLUSION: These results indicate that D1A
      dopamine receptors both of WKY rats and of SHR contain sulfhydryl groups at or
      near the ligand binding site, which display differential sensitivity to N
      ethylmaleimide.

PMID- 8762206
TI  - Characterization of ouabain-like immunoreactivity in human urine.
AB  - OBJECTIVE: To characterize ouabain-like immunoreactivity in human urine. METHODS:
      Sensitive radioimmunoassay for ouabain characterized by high-performance liquid
      chromatography. RESULTS: Serial dilution of urinary immunoreactive ouabain
      paralleled the standard curve, but not so plasma immunoreactive ouabain.
      Intravenous administration of 86 nmol (62.5 micrograms) ouabain caused a rapid
      rise in ouabain immunoreactivity in plasma of healthy volunteers with a maximum
      of 1.7 nmol/l 8 min after injection and returned to basal levels after 6 h.
      Ouabain immunoreactivity rose to 36 nmol/l in urine, suggesting that exogenously
      administered ouabain can be measured reliably in plasma and urine. Analytical
      reversed-phase high-performance liquid chromatography (isopropanol-propanol
      biphasic gradient; linear acetonitrile gradient) of sample extracts before assay
      demonstrated measurable amounts of ouabain-related material only in native urine,
      but not in plasma. When plasma and urine were spiked with ouabain standard or
      normal volunteers were injected with ouabain, the assay reliably measured
      ouabain. CONCLUSION: A substance closely related to ouabain can be detected in
      urine, but circulates, if at all, in small amounts in human plasma.

PMID- 8762207
TI  - Coagulation and fibrinolytic factors in normotensive hypertension-prone men.
AB  - OBJECTIVE: To evaluate whether a family history of hypertension is associated
      with disturbances in the coagulation and fibrinolytic systems. SUBJECTS: Thirty
      five normotensive men with a family history of hypertension (relatives) and 27
      age- and body mass index-matched controls with a family history (controls).
      METHODS: Insulin sensitivity was determined with a euglycaemic hyperinsulinaemic
      clamp technique. Maximal oxygen uptake was estimated from a submaximal work test.
      Blood samples were analysed for several coagulation and fibrinolytic factors.
      RESULTS: Relatives had higher plasma levels of plasminogen activator inhibitor-1.
      Levels of plasma factor VII, prothrombin fragments 1 and 2, fibrinogen and von
      Willebrand factor antigen did not differ significantly between the groups.
      However, antithrombin III, protein C and protein S levels were higher in the
      relatives than in the controls. Coagulation and fibrinolytic factors correlated
      to waist circumference, insulin sensitivity, maximal oxygen uptake and serum
      triglycerides level. CONCLUSIONS: Normotensive men with a family history of
      hypertension have an inhibited fibrinolysis, but also higher levels of several
      anticoagulant factors. The clinical application of these findings for the future
      development of cardiovascular disease warrants additional studies.

PMID- 8762208
TI  - Low magnesium enhances the pro-arrhythmic effect of low potassium in the
      hypertrophied rat heart but not in the normal rat heart.
AB  - OBJECTIVES: To investigate the influence of external magnesium on wall stress
      induced arrhythmias and to establish whether early cardiac hypertrophy affects
      the sensitivity of the heart to these arrhythmias. METHODS: We used a modified
      isolated working heart model to compare hypertrophied hearts from the
      spontaneously hypertensive rat (SHR) with hearts from normotensive control rats
      from the Wistar and Wistar-Kyoto strains. Young rats (aged 137.9 +/- 2.04 days
      mean +/- SEM) were used to ensure left ventricular hypertrophy uncomplicated by
      fibrosis and cardiac failure. Arrhythmias were induced by 20 s increases in
      ventricular afterload during which the electrocardiogram was recorded. RESULTS:
      In control experiments SHR hearts showed a significantly greater arrhythmic
      response than did normotensive control rat hearts during perfusion with low
      potassium (2.4 mmol/l) solutions. Concomitant low magnesium (0.4 mmol/l)
      perfusion significantly increased the arrhythmic response to 2.4 mmol/l potassium
      in SHR hearts but had no effect on arrhythmias in normotensive control rat
      hearts. With low magnesium, the number of ventricular premature beats was
      increased in SHR hearts compared with that in normotensive control rat hearts
      during perfusion with 4.2 and 2.4 mmol/l potassium. In addition, perfusion with
      low magnesium and 2.4 mmol/l potassium led to an increase in the complexity of
      arrhythmias, ventricular tachycardia occurring in nine of 10 SHR hearts but in
      only two of six normotensive control rat hearts. CONCLUSIONS: There is a
      synergistic effect of low magnesium and low potassium on wall-stress-induced
      arrhythmia in the SHR heart. An analogous effect might be important in patients
      with hypertension and left ventricular hypertrophy, in whom systolic blood
      pressure is frequently labile, leading to wide fluctuations in ventricular wall
      stress; combined potassium and magnesium depletion is a common complication of
      antihypertensive treatment.

PMID- 8762209
TI  - Losartan reduces cardiac mass and improves coronary flow reserve in the
      spontaneously hypertensive rat.
AB  - OBJECTIVES: To evaluate the effects of losartan administration on cardiovascular
      mass, systemic and coronary hemodynamics (rest, maximal treadmill exercise, and
      dipyridamole infusion) and on resting regional hemodynamics in conscious
      spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. RESULTS:
      Although losartan administration (two doses: 10 and 30 mg/kg per day for 3 weeks
      by gavage) reduced left ventricular mass at the higher dose in WKY rats and with
      both doses in SHR, only the higher dose reduced arterial pressure in SHR.
      Losartan administration did not affect cardiac index, myocardial or other organ
      flows (radiomicrosphere) at rest in both strains. Significant increases in
      cardiac index and coronary flow and decreases in coronary vascular resistance
      were observed during exercise in both strains and these responses were not
      affected by losartan administration. Compared with those in WKY rats, coronary
      flow and flow reserve (dipyridamole) were decreased and minimal coronary vascular
      resistance was increased in untreated SHR. Administration of a higher losartan
      dose increased coronary flow reserve and decreased minimal coronary vascular
      resistance (measured during dipyridamole infusion) in SHR. CONCLUSIONS: These
      data demonstrated that losartan administration reduced left ventricular mass, a
      response that did not seem to be solely dependent on afterload. Furthermore,
      cardiac and stroke indices and coronary flow reserve were not changed in SHR
      during maximal treadmill exercise after hypertrophy reversal, even with the lower
      dose of losartan and when the ventricular afterload was similar to that of
      untreated SHR.

PMID- 8762210
TI  - Albuminuria in normotensive and hypertensive individuals attending offices of
      general practitioners.
AB  - OBJECTIVE: To investigate the rate of albumin excretion and the prevalence of
      albuminuria in hypertensive individuals relative to the normotensive population,
      and to clarify the quantitative importance of confounding variables. DESIGN AND
      METHODS: We examined the morning urines of all consecutive non-diabetic and
      diabetic hypertensive patients (n = 631; 371 women, 260 men) attending the
      offices of five general practitioners in a circumscribed geographical area during
      a 4-month period. To obtain a normotensive control population, all consecutive
      visitors (n = 375; 217 women, 158 men) were also examined. Urinary albumin
      excretion was assessed by kinetic nephrelometry in morning urine samples.
      RESULTS: The median albumin excretion rate was 4.3 micrograms/ml (range 1.9-112)
      in normotensive individuals; 3.4 micrograms/ml (1.9-1440) in hypertensive and 3.6
      micrograms/ml (1.9-2790) in diabetic patients (n = 189; 115 women, 74 men). The
      overall prevalence of albuminuria above 20 micrograms/ml was 4% in normotensive
      individuals, 10% in hypertensive patients and 17% in diabetic patients. The
      proportion of patients with higher-grade albuminuria (> 50 micrograms/ml) was 1%
      among the normotensive subjects aged below 60 years and 2% in those aged above 60
      years; the respective values in hypertensive patients were 3 and 6% and in
      diabetic patients 8 and 13%. The multivariate regression analysis showed a
      significant correlation between albuminuria and smoking (P < 0.0001), the
      presence of hypertension (P < 0.001), the current level of systolic blood
      pressure (P < 0.01) and age (0.031), but not sex or body mass index. CONCLUSIONS:
      The present study confirms a higher prevalence of albuminuria above 20
      micrograms/ml in individuals with primary hypertension and diabetes mellitus
      compared with that in normotensive subjects, despite similar median albumin
      excretion rates. However, the excess of prevalence is moderate. Smoking, advanced
      age and current level of systolic blood pressure are the important determinants.

PMID- 8762211
TI  - Trough:peak ratio of nifedipine gastrointestinal therapeutic system and
      nifedipine retard in essential hypertensive patients: an Italian multicentre
      study.
AB  - OBJECTIVE: To evaluate the antihypertensive effect of nifedipine gastrointestinal
      therapeutic system and retard in terms of trough:peak ratio efficacy. METHODS:
      According to a double-blind, randomized, crossover design, 58 patients with mild
      to-moderate essential hypertension, after 1 month placebo washout, received 30
      mg/day nifedipine gastrointestinal therapeutic system, 20 mg nifedipine retard
      twice a day and the corresponding placebos for 1 month. At the end of each
      treatment period, blood pressure was measured by using a mercury sphygmomanometer
      at trough and 1, 2, 3 and 4 h after the last dosing. The peak effect was
      identified as the maximum decrement induced by the three randomized treatments
      with respect to the value at the end of the placebo washout period during the 4 h
      interval. The trough:peak ratios of systolic and diastolic blood pressure were
      calculated as group ratios and individual ratios from decrements induced by
      nifedipine gastrointestinal therapeutic system and retard, corrected for those
      induced by randomized placebo. Patients were defined as responders to each
      randomized treatment if their diastolic blood pressure at trough time was reduced
      by at least 10 mmHg relative to that at the corresponding time at the end of
      placebo washout. RESULTS: Nifedipine gastrointestinal therapeutic system and
      retard significantly reduced blood pressure to a similar extent both at trough
      and at peak. Systolic and diastolic group trough:peak ratios in responders to
      nifedipine gastrointestinal therapeutic system (n = 41) were 0.80 and 0.88,
      respectively, and those in responders to nifedipine retard (n = 30) 0.84 and
      0.93, respectively. The percentage of patients with trough:peak ratios > 0.50 was
      > 80% (systolic trough:peak ratios) and above 90% (diastolic trough: peak ratios)
      for both nifedipine formulations. CONCLUSIONS: Our data show that 30 mg/day
      nifedipine gastrointestinal therapeutic system and 20 mg nifedipine retard twice
      a day have a favourable trough:peak ratios efficacy when given as monotherapy to
      essential hypertensive patients.

PMID- 8762213
TI  - Nocturnal blood pressure fall depends on the period chosen.

PMID- 8762212
TI  - Metabolic neutrality of combined verapamil-trandolapril treatment in contrast to
      beta-blocker-low-dose chlortalidone treatment in hypertensive type 2 diabetes.
AB  - OBJECTIVE: To investigate the metabolic, antihypertensive and albuminuria
      modifying effects of a heart rate-modulating calcium antagonist-angiotensin
      converting enzyme inhibitor combination compared with those of a beta-blocker-low
      dose diuretic combination in non-insulin-dependent diabetic hypertensives.
      DESIGN: A prospective randomized double-blind study. SUBJECTS AND METHODS: Twenty
      four diabetics with diastolic blood pressure 90-115 mmHg without azotemia (plasma
      creatinine level < 150 mumol/l) were evaluated after 4 weeks receiving placebo
      and 12 weeks receiving treatment either with combined slow-release verapamil
      (retard formulation) and trandolapril (mean maintenance doses, 180 and 1.6 mg
      daily) or with atenolol and chlortalidone (71 and 18 mg daily). Insulin
      sensitivity (by the minimal model method of Bergman), additional metabolic
      variables, clinic blood pressure, ambulatory blood pressure profile and renal
      indices were assessed at the end of the placebo and active treatment phases.
      RESULTS: Compared with placebo, the two therapies produced similar decreases in
      mean supine clinic blood pressure [10 +/- 3 versus 11 +/- 3% (means +/- SEM)],
      upright clinic blood pressure (10 +/- 4 versus 11 +/- 4%) and ambulatory daytime
      blood pressure (9 +/- 2 versus 12 +/- 3%). However, although the verapamil
      trandolapril combination was found to be metabolically neutral, the atenolol
      chlortalidone combination aggravated insulin resistance [insulin sensitivity
      index, from (0.8 +/- 0.2) to (0.3 +/- 0.1) x 10(-4)/min per U per ml], increased
      the serum triglycerides level and decreased the high-density lipoprotein
      cholesterol and plasma potassium levels. Although both therapies tended to reduce
      24 h albuminuria, this was significant for the verapamil-trandolapril treatment
      only. CONCLUSIONS: Because the effect of any antihypertensive drug, including
      diuretics and beta-blockers, on cardiovascular morbidity and on mortality in non
      insulin-dependent diabetic patients is not known, rational treatment selection
      can presently be based only on surrogate end-points. Therefore, the triad of
      metabolic neutrality with antihypertensive and antiproteinuric efficacy supports
      combined verapamil-trandolapril as a potentially valuable therapy for
      hypertension accompanying diabetes mellitus.

PMID- 8762214
TI  - Long term reproducibility of ambulatory blood pressure monitoring.
AB  - The long term reproducibility of ambulatory blood pressure measurements was
      evaluated over two 24 h recordings made under identical conditions 2 years apart
      in 20 normotensive and 13 essential hypertensive patients not receiving
      antihypertensive treatment. There was excellent agreement between the mean 24 h
      values of blood pressure as well as for the day time and night time means. The
      standard deviation of the differences was half that of casual determinations. On
      the other hand, the reproducibility of the mean hourly values was comparable to
      that of casual measurements. The reproducibility of the white coat effect was
      poor, as assessed by the difference between blood pressure on fitting the device
      and the mean day time value. These results indicate that the short term
      reproducibility of ambulatory blood pressure is maintained over the long term.

PMID- 8762215
TI  - Drug-induced changes in ambulatory blood pressure and pulse pressure in patients
      with or without sustained hypertension.
AB  - We retrospectively studied 216 mild to moderate hypertensive patients receiving
      either an angiotensin converting enzyme inhibitor (ACEI) or a calcium antagonist
      (CA), as a once-a-day monotherapy; their blood pressure had been measured using
      both a sphygmomanometer and an ambulatory blood pressure recorder. Numerous
      discrepancies were found between the two methods of blood pressure measurement
      with respect to systolic blood pressure (SBP) and diastolic blood pressure (DBP),
      as well as pulse pressure (PP). Clinic blood pressure measurement did not show
      any significant differences between the effects of ACEI and those of CA, whereas
      ambulatory blood pressure measurements (ABPM) showed that in patients with normal
      ambulatory blood pressure (so-called 'white coat' hypertensive patients), ACEI
      only (but not CA) significantly lowered SBP, DBP and PP. Accordingly, a threshold
      of efficacy was sought: it appeared to be lower for ACEI than for CA (120/80 vs
      140/85 mmHg). Furthermore, for a given degree of DBP lowering, SBP and PP were
      more lowered by ACEI than by CA, indicating a greater effect of ACEI on arterial
      compliance. Likewise, for a given level of mean blood pressure, SBP and PP were
      lower and DBP slightly higher in patients on ACEI than in those on CA. Our data
      are consistent with some recent papers, emphasizing a heightened activity of the
      renin-angiotensin system in 'white coat' hypertensive patients.

PMID- 8762216
TI  - [Pharmaco-clinical correlations during fluoxetine administration in patients with
      depressive schizophrenia treated with haloperidol decanoate].
AB  - The study concerned 7 patients suffering from schizophrenic disorder according to
      the DSM III R criteria, treated with a stable dose of haloperidol decanoate
      (Haldol decanoas) added with fluoxetine (Prozac) from 20 mg to 40 mg/day because
      of major depression. Patients were assessed at baseline and weekly during the
      first cycle, and then once a month before each haloperidol decanoate injection,
      using the brief psychiatric rating scale (BPRS), the general clinical impression
      scale (CGI) and the Montgomery and Asberg depression rating scale (MADRS).
      Extrapyramidal and anticholinergic side-effects, blood pressure and pulse were
      noted. Determinations of plasma and red blood cells concentrations of haloperidol
      and reduced haloperidol, and of fluoxetine and norfluoxetine, were conducted at
      the same time than clinical evaluations. For all patients, we observed an
      improvement by the end of the first week, which became significant at the end of
      the second week, and continued in subsequent weeks (more than 30 per cent). Two
      weeks after the addition of fluoxetine, a very significant increase in
      haloperidol concentrations (more than 100 per cent) was noted; fluoxetine seems
      to have pharmacokinetic interactions with haloperidol, either by inhibiting its
      hepatic metabolism (inhibition of cytochrome P450 isoenzyme) or/and by displacing
      it from protein binding sites.

PMID- 8762217
TI  - [Comparison of clinical and ambulatory measurements of blood pressure with
      benazepril alone or combined with hydrochlorothiazide in hypertension].
AB  - The aim of this study was to analyse the respective values of clinic and
      ambulatory blood pressure measurements in patients with treated hypertension.
      Twenty-eight patients with mild to moderate hypertension were studied (clinic
      blood pressure > or = 160/95 mmHg), treated with benazepril alone (n = 7) or
      combined with hydrochlorothiazide (n = 21). A 24 h ambulatory blood pressure
      measurement was performed before (d0) and after 8 weeks of treatment (d56). The
      treatment was effective on the ambulatory blood pressure in 19 patients (Staessen
      criteria) and effective on clinic measurements in 20 patients (WHO criteria). The
      results were concordant in 25 of the 28 patients. The decrease of the ambulatory
      blood pressure values during the day between d0 and d56 was not significantly
      related to the decrease of the clinic values. The comparison of the ambulatory
      blood pressure values at each hour between d0 and d56 showed that the treatment
      was effective during 24 h. The 'white coat' effect has been evaluated at d0 and
      d56 by the difference between mean daytime ambulatory blood pressure and clinic
      values. Clinic values were higher than mean daytime ambulatory values in
      benazepril (14 +/- 12 mmHg and 7 +/- 7 mmHg for the systolic and diastolic
      pressure) and benazepril-hydrochlorothiazide group (12 +/- 12 mmHg and 0.2 +/- 9
      mmHg for the systolic and diastolic pressure). This 'white coat' effect was not
      modified during the treatment. Previous studies have emphasized a better
      assessment of the cardiovascular risk with ambulatory than with clinic
      measurements. The differences in the assessment of the efficiency of the
      treatment between clinic and ambulatory measurements shown in our study prompt us
      to use ambulatory measurements in patients with apparently uncontrolled
      hypertension.

PMID- 8762218
TI  - [Double blind randomized comparative study of two antihypertensive combinations.
      Enalapril-hydrochlorothiazide versus enalapril-nifedipine in 240 hypertensive
      patients resistant to monotherapy].
AB  - The combination of two antihypertensive drugs is recommended when mild to
      moderate hypertension is not controlled by sequential monotherapy. The aim of our
      study was to compare the efficacy and the safety of the combination enalapril 20
      mg-hydrochlorothiazide 12.5 mg to that of enalapril 20 mg-nifedipine SL 20 mg x
      2. Two hundred and forty four hypertensive patients not controlled (DPB > 95
      mmHg) by a single dose of enalapril 20 mg/24 h, received for 4 weeks, one of
      these two combined therapies in a randomized double-blind trial. The efficacy was
      of same amplitude in the two groups (DBP: -10.8 mmHg enalapril
      hydrochlorothiazide vs-10.3 mmHg enalapril-nifedipine). The side effects were
      less frequent in the enalapril-hydrochlorothiazide group (14 per cent vs 24 per
      cent, p = 0.04).

PMID- 8762219
TI  - Equivalent effects of nicardipine and captopril on urinary albumin excretion of
      type 2, non-insulin-dependent diabetic subjects with mild to moderate
      hypertension.
AB  - To test if calcium antagonists and converting enzyme inhibitors can act similarly
      on urinary albumin excretion of type 2, non-insulin-dependent diabetic subjects
      with hypertension, a 24 week, double-blind, randomized, parallel multicentre
      study was performed in 111 such patients allocated to nicardipine 50 mg slow
      release form (n = 57) or to captopril 25 mg (n = 54) twice daily. The efficacy of
      both drugs was similar on urinary albumin excretion (Westlake test p = 0.19).
      However, blood pressure was lower on nicardipine than on captopril (p < 0.05),
      and the antialbuminuric effect of nicardipine was related to its hypotensive
      effect, while this was not the case for captopril. The two drugs were tolerated
      equally. Thus, nicardipine and captopril for 24 weeks can be equally effective on
      urinary albumin excretion of type 2, non-insulin-dependent diabetic subjects with
      hypertension, but the mechanisms of their anti-albuminuric effects may be
      different.

PMID- 8762220
TI  - [Diuretics in the treatment of hypertension: critical analysis of opinions of
      general practitioners and cardiologists].
AB  - To better evaluate the clinical practice of French practitioners regarding the
      treatment of hypertension and the use of diuretics, we conducted a study using
      quota method to select 240 general practitioners and 90 cardiologists. Diuretics
      are still widely used and are effective well known drugs. Their use is
      nevertheless restricted by some side effects such as increasing frequency of
      micturition and electrolyte disturbances. These side effects are reduced with the
      new lower dosages and slow release formulations. Analysis of the results of our
      study suggests that the use of diuretics depends more on old habits and industry
      communication on drugs than on the knowledge of the results of therapeutic trials
      on mortality and morbidity.

PMID- 8762221
TI  - [Reflexions before the introduction of a drug prescription survey at hospitals].
AB  - The need to know about drug prescribing practices, in order to assess their
      relevance, has led us to perform a drug prescription study in two medical
      departments of Cardiology at 'Neuro-Cardiologique Hospital' in Lyon (France). In
      moving from theoretical project design to its practical achievement, important
      methodological problems, initially unsuspected, were encountered. For each main
      point of the study (choices regarding medical department, the person holding the
      inquiry, data collection, etc.) and any subsidiary operations (data key-boarding,
      codification and analysis), the main problems encountered are described after
      considering advantages and limits of potential solutions. We propose useful and
      relevant questions to be asked, before performing a drug prescription study, even
      a modest one, or interpreting the results of such a study.

PMID- 8762222
TI  - [Hormone replacement treatment and skin aging].
AB  - Ageing of the skin results from the synergistic effects of intrinsic ageing (due
      to age and genetic factors), photoageing (due to ultraviolet radiation) and, for
      women, hormonal ageing (due to oestrogen deficiency in postmenopausal women).
      Oestrogens receptors and metabolism or inactivation of oestradiol have been
      demonstrated in the skin, and the pilosebaceous unit is a target for sexual
      steroids. Could hormonal replacement therapy (HRT) be a treatment for the
      symptoms of skin ageing (dryness, roughness, burning and atrophy of the skin,
      itching, cold intolerance, wrinkles, hyperpilosity, alopecia)? In some
      experimental studies oestrogens increase the activity of fibroblasts and water,
      hyaluronic acid and collagen dermal contents. Some studies have demonstrated that
      oestrogen treatment increases skin thickness, mitotic activity of keratinocytes,
      and dermal collagen content in postmenopausal women. Thus HRT could theoretically
      treat skin ageing. It has been shown that HRT alleviates some symptoms of skin
      ageing (dryness of hair and skin) and that flushes disappear. We demonstrated
      that non-invasive measurements of physical parameters of the skin can reveal
      increase in skin thickness (+10 to +20 per cent) in women treated by HRT vs non
      treated, especially in the application area of oestrogen and in the non-sun
      exposed areas. In our study HRT alleviated the hyposeborrhoea usually seen after
      menopause and could contribute to the amelioration of some complaints of post
      menopausal women such as roughness or dehydrated skin. Hormonal ageing is
      quantitatively less than actinic ageing, but its treatment is easier. Moreover
      HRT increases skin thickness, contributing to the prevention of atrophy (with
      fragile and fading skin) due to intrinsic ageing, and it limits the
      masculinization of facial hair and skin experienced by women as a sign of ageing.
      In conclusion HRT treats oestrogen deficiency and can be used to treat skin
      ageing.

PMID- 8762224
TI  - [XIVth Consensus Conference in Intensive Care and Emergency Medicine. Management
      of status epilepticus (children-adults)].

PMID- 8762223
TI  - [XIIIth Consensus Conference in Intensive Care and Emergency Medicine. Assisted
      respiration during acute decompensation in chronic respiratory failure in adults
      (excluding neuromuscular pathology and weaning)].

PMID- 8762225
TI  - [Antibiotic-associated pseudomembranous colitis: retrospective study of 48 cases
      diagnosed by colonoscopy].
AB  - Pseudomembranous colitis (PMC) is a rare but potentially severe complication of
      antibiotic treatment, which is characterized by the proliferation of the
      bacterium Clostridium difficile in the colon. In this retrospective study, 48
      cases of endoscopically confirmed PMC were included. The following variables were
      analysed: characteristics of the patients, antibiotics, clinical, biological and
      endoscopic features of PMC and its treatment. The antibiotic treatment was often
      ambulatory (83 per cent) for a broncho-pulmonary infection (42 per cent). In 90
      per cent of the cases, the treatment included a -lactam, frequently amoxicillin
      with clavulanic acid, and in 25 per cent of the cases, a fluoroquinolone. The PMC
      generally occurred after more than 4 days of treatment and was associated with
      diarrhoea, abdominal pain, fever and rarely vomiting (23 per cent). The
      complications were hypokalaemia (37 per cent), renal failure (27 per cent) and/or
      hypoproteinaemia (50 per cent). Pseumembranes were found between the rectum and
      the left angle of the colon. All patients recovered after one week of oral
      treatment with metronidazole and/or vancomycin, often in association with
      Saccharomyces boulardii.

PMID- 8762226
TI  - [Severe and transient acute myositis after mumps vaccination (Imovax-Oreillons)].

PMID- 8762228
TI  - [From synthesis of immunoglobulins E to allergic syndromes].
AB  - Allergic reactions consist to a cascade of pathological events which are
      initiated by the activation of the immune system. These reactions result in a
      hypersensitivity state characterized by multiple parameters. Clinical symptoms
      among allergic population are characterized in a proportion of 75% of allergic
      individuals by a mechanism of immediate hypersensitivity, or IgE-dependent
      allergic reactions. Several conditions need to be met for the immediate
      hypersensitivity to occur: genetic background, the nature of allergens and the
      route of administration, the cytokine-dependent immunoregulatory mechanisms of
      IgE production, the threshold of reactivity of inflammatory cells, the amount of
      inflammatory mediators released, and the environmental factors. Therefore, the
      clinical expression of IgE dependent hypersensitivity results from a complex
      network of interactions between the host and its environment.

PMID- 8762227
TI  - [Bioavailability and tolerance of indomethacin as polymeric mini-capsules in
      man].

PMID- 8762229
TI  - [Pollinosis].
AB  - Pollinosis is an extremely common disorder affecting between 10 to 30% of the
      population. There are regional and seasonal variations with allergies occurring
      between february (in south of France) and autumn. Pollen calenders allow one to
      identify the pollens specific to each region. Treatment is based on the
      utilisation of antihistaminic and local antiinflammatory agents. Specific
      desensitization is efficacious when quality extracts are used, but should be
      reversed for particular cases as the therapeutic risk should in no case exceed
      that of the illness.

PMID- 8762230
TI  - [Allergic asthma].
AB  - During the last decade, the prevalence of allergic asthma has increased in
      France, as well as in most developed countries. The clustering of symptoms of
      dyspnoea, chest tightness, wheeze, and their intermittent nature usually leads to
      a diagnosis of asthma. Nevertheless physicians should be aware of some atypical
      presentations such as recurrent infections, wheezing bronchitis, exercise induced
      dyspnoea or chronic cough. Physicians have also to recognize early symptoms of an
      acute severe asthma. For the identification of the allergen(s) responsible for
      asthma, data obtained from clinical history, from cutaneous prick tests
      eventually associated to serum specific IgE antibodies have to be taken in
      account. The assessment of severity of asthma is another essential point: it
      needs to be documented by using pulmonary function tests and in more severe forms
      of asthma on regular measurements of peak expiratory flow rate.

PMID- 8762231
TI  - [Drug allergy].
AB  - Drug allergies represent about 10% of all adverse drug reactions. According to
      the Gell and Coombs classification, they are based on immunological mechanisms,
      with sensitization during the first contact, and later a clinical and (or)
      biological reaction after the second contact. Metabolism of drugs, often
      genetically determined, results in reactive metabolites which conjugate with
      endogenous proteins to become immunogenic. Anaphylaxis induced by myorelaxant
      drugs and beta-lactams, and delayed type drug eruptions are discussed as
      examples. All acute drug reactions are not, however, anaphylactic. Many
      exanthematous reactions occurring during antibiotic treatment are in fact caused
      by a virus.

PMID- 8762232
TI  - [Food hypersensitivities].
AB  - Food hypersensitivity includes adverse reactions to food which are most often
      mediated by IgE. Food allergy is the first atopic disease. Food-sensitized
      individuals can develop allergic reactions such as atopic dermatitis, urticaria,
      angioedema, rhinitis, asthma or digestive symptoms. Anaphylactic shock is the
      most severe reaction of immediate hypersensitivity. The prevalence of food
      allergy has drastically increased during the last years. Numerous food products
      can be involved, with special emphasis on masked allergens in processed foods.
      The diagnosis of food hypersensitivity is based on clinical history, analysis of
      patient's food intake, skin tests and placebo-controlled food challenge tests.
      Oral food-challenge tests allow a distinction between food sensitization and true
      food hypersensitivity. Treatment consists in avoidance of the offending food
      allergen associated with adjunctive therapy by antihistamines and disodium
      cromoglycate. The prescription of a first-aid kit is required in case of
      anaphylaxis. Specific immunotherapy seems to be an interesting therapeutic
      prospect. Prevention remains essential.

PMID- 8762233
TI  - [The allergic skin].
AB  - The main cutaneous manifestation of allergy is eczema. In atopic dermatitis, the
      epidermal Langerhans cells express receptors for IgE and the eczematous lesions
      may be associated with other atopic disorders such as asthma or pollinosis. In
      contact dermatitis, the epidermal Langerhans' cells play the role of antigen
      presenting cells; the antigens eliciting the eczematous lesions may be of
      occupational, vestimentary, cosmetical, therapeutical or other environmental
      origin. Epicutaneous test procedures enable their identification. Paraptic eczema
      is a concept including all the cutaneous and systemic complications of contact
      dermatitis.

PMID- 8762235
TI  - [Allergic emergencies].
AB  - Some allergenic aggressions produce life threatening reactions requiring an
      emergency treatment. Anaphylaxis is related to relatively isolated exposures:
      drugs, food, hymenoptera stings. Anaphylactic shock is a life threatening
      reaction due to several mechanisms of mast cells degranulation. Exercise-induced
      anaphylaxis is sometimes symptomatic of food allergy, and idiopathic anaphylaxis
      may also represent a severe reaction. Adrenaline is the mainstay for emergency
      treatment; it has to be used as soon as possible, according to correct procedures
      as a first-step treatment. Emergency treatment may also be required after an
      allergenic exposure, especially fungal, responsible for allergic asthma
      exacerbation, severe cutaneous or mucosal lesions (laryngeal oedema,
      angiooedema...).

PMID- 8762234
TI  - [Allergic children].
AB  - Epidemiologic data have shown an increased prevalence (and severity) of atopy
      related diseases (asthma, eczema and allergic rhinitis) during the post 15-20
      years. Atopic respiratory diseases such as allergic rhinitis and asthma represent
      the effects of an immunological response to allergens, mediated through
      immunoglobulins E. Development of a clinically significant atopic reaction
      depends on environmental exposure. The majority of allergic children display
      positive skin tests to house dust mites, animal danders or pollens. Immediate
      hypersensitivity to food allergens starts early in life and is most often
      associated with atopic dermatitis. Allergic reactions to peanuts are generally
      acute and severe, with an increasing frequency. Parents must be aware of their
      child's problem and preventive measures must be undertaken very early in life,
      first at home and later also at school. Family history remains the best predictor
      of atopy in newborn babies.

PMID- 8762236
TI  - [Specific treatments of allergic manifestations].
AB  - Because we now know more about the relationship between environment and allergy,
      we should aim: at preventing allergic diseases in at-risk populations; at
      alleviating symptoms in sensitized patient using avoidance methods; and at
      modifying immunological responses through specific immunotherapy. Recent studies
      provide a better knowledge of the allergenic levels which induce sensitization
      and trigger symptoms in allergic patients. This knowledge allows a strategy for
      avoidance measures. A better understanding of cross allergenicity of several
      allergens has been drawn from a better knowledge of the epitopes. Specific
      immunotherapy has proven its efficacy in selected patients suffering from asthma
      and/or rhinitis and patients with hymenoptera sensitivity.

PMID- 8762237
TI  - [Interpretation of an epidemiological survey. Survey types, concepts of bias,
      causality].

PMID- 8762238
TI  - [Cancer of the stomach. Diagnosis, development, treatment].

PMID- 8762239
TI  - [Neurotic syndrome: obsessive neurosis. Diagnosis, treatment].

PMID- 8762240
TI  - [Inguinal, crural, umbilical hernias. Physiopathology, diagnosis, complications,
      treatment].

PMID- 8762241
TI  - [Non-morphine analgesics. Principles and rules of use].

PMID- 8762242
TI  - [Alcoholism].

PMID- 8762244
TI  - ["To submit a complaint." The language of patients with chronic pain].

PMID- 8762245
TI  - [Value of selective prescription of preanesthetic laboratory tests].
AB  - The aim of this study was to determine the comparative value of routine or
      selective ordering of preoperative tests. 400 ASA I, II, III patients were
      enrolled in the study. Two periods were considered: a retrospective period where
      the patients (n = 200) underwent routine preoperative tests and a prospective
      period where the patients (n = 200) had only preoperative tests according to the
      results of questioning and clinical examination. During the retrospective period
      1.408 tests were effected with 44 abnormal results. During the prospective
      period, the abnormal results among 855 prescribed tests were: 0.8% in ASA I
      patients, 7.5% in ASA II and 5.9% in ASA III patients. The ASA I patients had an
      average of 3.47 +/- 1.28 tests each, ASA II patients 4.50 +/- 1.21 and ASA III
      7.50 +/- 1.50. No complication inducing sequelae or death could be linked to
      lacking tests. The mean cost of tests was reduced by 50 percent.

PMID- 8762246
TI  - [Attempted suicide in the aged].
AB  - Elderly people suicide or attempted suicide commands reflection. Some suicide
      leading factors provide conspicuous risk markers. This retrospective analysis of
      141 patients older than 65 yr, admitted in Lorient hospital emergency unit
      between 1986 and 1995, confirms the reality of risk factors, allowing to sketch a
      portrait of potential suicides so that preventive actions could be taken.

PMID- 8762247
TI  - [What surgical indications remain in the treatment of pain?].
AB  - 26 out of 39 pain treatment centres answered a questionnaire about surgical
      management of chronic pain. 12,715 patients have been seen during 1992, suffering
      mainly from lumbosciatalgia, peripheral nervous system lesions (20% of iatrogenic
      origins) or cancer pain. 1,635 underwent a surgical procedure on: lumbar chain
      (520), Vth cranial nerve (448), spinal cord (225 electrical stimulations),
      splanchnic nerves (171). Ablative surgery on somatic nerves retains only minor
      indications, in contrast to an increase in the frequency of stimulation
      techniques.

PMID- 8762248
TI  - [Computerized anesthesia record. How far have we gone?].
AB  - There are more and more computerized anaesthetic records becoming available from
      various constructors. However, the setting up and operation of such a product
      depends on the development of concepts in computing. The second technological
      breakthrough, currently underway, is challenging principles which had seemed
      accepted up until now. The technical development concerns computer processing
      units, RAM or ROM. The development in software influences the operation of
      networks, multiple task and object programming. The graphic interface becomes the
      centre of this second revolution. All of these developments should be included in
      the proposed computerized anaesthetic records. Three factors determine the
      realisation of such a product: control of the data collecting process, the man
      machine interface and the utilisation of storing data. The computerized
      anaesthetic record should be of open conception, allowing communication with all
      of the data bases and providing an interface with all the monitors and
      ventilators used in operating and recovery rooms. Now is the time to install the
      infrastructure network in operating and recovery rooms and to be thinking of
      acquiring the new generations of computerized anaesthetic records.

PMID- 8762249
TI  - [Sufficient autotransfusion with a single-use device in experimental vascular
      surgery].
AB  - The authors used a disposable original system to recover total blood during
      surgery and realized 17 transfusions of autologous blood in sheep. No biological
      or clinical disturbance was observed.

PMID- 8762250
TI  - [Iatrogenic laryngotracheal stenosis. A follow-up of 20 recent cases].
AB  - The aim of this study was to analyse the follow-up of patients with a history of
      endotracheal intubation and/or tracheotomy because of respiratory distress,
      surgical necessity or long-term resuscitation. Twenty adults were followed up in
      a ENT facility for laryngeal or tracheal stenosis, of which 7 cases were
      diagnosed during 1994. This study shows that, in patients with a history of
      intubation, or intubation followed by tracheotomy, the stenosis developed within
      two months after resuscitation with a favourable outcome. After tracheotomy only,
      the stenosis developed later (2 months or more) with more recurrences. The
      diagnosis of stenosis was made on gradual or acute dyspnea. While respiratory
      resuscitation methods are essential and often life-saving, they are not without
      complications. Laryngeal and tracheal stenosis could be largely prevented by more
      careful techniques of endotracheal intubation and tracheotomy. Periodic
      endoscopic airway surveillance is useful to detect stenosis even when there is no
      clinical symptom.

PMID- 8762251
TI  - [Postoperative autotransfusion and transfusion evaluation in cardiac surgery].
AB  - In cardiac surgery, blood retransfusion from the thoracic drainages, though
      already ancient, still remains controversial either for its quantitative or its
      qualitative interests. A retrospective study has been conducted, between the 1st
      january 1992 and the 30th june 1993, over 1.655 consecutive operations. Most of
      the patients suffered from coronary disease (937) or a valvular disease (605),
      others had been operated for a combined valvular and coronary revascularization
      surgery (113). The safety of this technique, guaranteed by strict rules, allowed
      a "transfusional strategy" which tends to reduce the homologous blood
      consumption. Twenty-nine percent of all the patients received homologous red
      cells units and only 23% of the patients operated for a coronary
      revascularization. This strategy aims to reduce both the risks of blood
      transfusion and the health cost.

PMID- 8762252
TI  - [Resuscitation in severe hepatic injuries].
AB  - Hepatic injuries account for about 45% of all abdominal traumas and for 30 to 40%
      of penetrating abdominal injuries. In 60% of the cases, they are associated with
      other lesions, especially life-threatening head injuries. Abdominal
      ultrasonography, a short and safe procedure enabling guided puncture, has
      developed rapidly relegating to the second rank other diagnostic techniques such
      as peritoneal lavage and CT scan. First line treatment of severe trauma
      complicated by haemorragic shock combines fluid resuscitation, prevention of
      hypothermia and administration of broad spectrum antibiotics. Surgical care,
      relying mainly on perihepatic packing and vascular exclusion techniques must
      remain as conservative as possible. Once haemodynamics have been stabilized in
      patients who do not present any other abdominal lesion requiring laparotomy, the
      non-interventional attitude is often successful and bears lower morbidity.

PMID- 8762253
TI  - [Intraosseous device of perfusion. Apropos of 3 cases before hospitalization].
AB  - A renewal of interest in the intraosseous route has appeared lately in France. It
      concerns pediatric patients. After anatomophysiological and technical quotes, we
      report the indications, contraindications, method of supervision and
      complications of the placement of an intraosseous infusion. Our modest experience
      enables us to present three observations where intraosseous route has been used
      outside hospital in children suffering a cardiopulmonary arrest on arrival of the
      practitioner belonging to the mobile emergency unit. This rapid and easy to place
      technique seems to be attractive as an alternative to the intravenous route in
      situations of utmost emergency, this all the more so since there are few reported
      contraindications and complications.

PMID- 8762254
TI  - [Ethylene glycol poisoning. Apropos of a case].

PMID- 8762255
TI  - [Plea for systematic preoperative tests].

PMID- 8762256
TI  - [Monitoring of intracranial pressure].
AB  - The use of intraparenchymatous ICP sensor is becoming increasingly popular at the
      expense of the traditional intraventricular catheter method, in spite of the
      impossibility, with the former technic, to correct a possible zero drift. The
      decision to initiate or discontinue ICP monitoring is essentially based upon
      whether suggestive aspects of raised ICP are or not present on CT-scan. The
      degree of basal cisterns effacement is particularly informative. The same data
      from successive CT-scans are used to check the validity of the monitoring.
      Predefining critical levels of ICP and cerebral perfusion pressure (CPP) allows
      to establish practical guide-lines for treatment. Cerebral ischemia is considered
      very likely when ICP rises above 30 mmHg. Regarding CPP, the therapeutical goal
      is to avoid its reduction under the critical level of 60-80 mmHg. As these
      thresholds vary with the patients age and the type of lesion, a parallel
      evaluation of cerebral ischemia by other methods is mandatory. Transcranial
      doppler allows an easy detection of critical reduction of arterial flow. However,
      in case of flow hypervelocity, interpretation needs measurement of absolute
      cerebral blood flow values. Cerebral venous oxygen saturation monitoring, at the
      level of the jugular golf, shows desaturation episodes indicative of cerebral
      ischemia. Blood sampling for determination of arterial and jugular venous lactate
      concentrations allows calculation of the lactate oxygen index, a practical
      correlate of the degree of cerebral ischemia. ICP measurement alone is of limited
      value to understand the cerebral hemodynamical and metabolical situation in
      severe brain injury. Preceding the rise of ICP, there exists a compensation phase
      during which a progressive decrease of intracranial compliance is the important
      event. Even more earlier, posttraumatic cellular metabolic dysfunctions are to
      day objectives for a neurochemical monitoring. Therefore a special technical and
      human environment has became mandatory to take a real benefit from ICP
      monitoring.

PMID- 8762257
TI  - [Inhalation anesthesia in unusual situations: the Eole 2 NA ventilator].
AB  - The volumetric ventilator Eole 2 NA has been adapted to work as an anaesthesia
      machine with low flow or closed system. This modified device is very easy to use
      in exceptional situations: because of its strength and reliability; its favorable
      quality/price ratio; versatile electrical supply: mains (220 volts) or 24 D.C.V.
      from internal battery (2 hours autonomy) or external battery (8 hours autonomy);
      gas economy: less than 1 L.min-1 of fresh gas flow, whether O2/N2O = 0.5 L.min-1
      of each gas or 1 L.min-1 delivered by an oxygen concentrator. Clinical trials are
      discussed.

PMID- 8762258
TI  - [Study of a protocol of intra-articular analgesia after arthroscopy of the knee].
AB  - The purpose of this study was to assess the analgesic effects of intra-articular
      injection of a morphine-bupivacaine combination following knee arthroscopy. 47
      patients were evaluated. Knee arthroscopies were all performed under general
      anaesthesia, using propofol, alfentanil, isoflurane and nitrous oxide. Analgesic
      effects were evaluated by a visual analogic pain scale. Serum bupivacaine was
      measured during the first 8 postoperative hours. Analgesia was good in the
      immediate postoperative period, with minimal side effects. The serum bupivacaine
      levels were low. However the analgesic efficacy of intra-articular injection of
      morphine-bupivacaine should be corroborated through a double blind study.

PMID- 8762259
TI  - [Factors promoting incidents during laparoscopic surgery in pediatrics].

PMID- 8762260
TI  - [Surgeon's role in the screening of breast cancer].

PMID- 8762261
TI  - [Technique and results of colonic esophagoplasties].
AB  - From 1985 to 1995, 60 patients with a mean age of 52 +/- 12 years [24-78]
      underwent colon interposition for esophageal replacement. Indications were
      esophageal cancer (n = 37), benign stricture (n = 13), iatrogenic esophageal
      fistula (n = 5), achalasia with megaesophagus (n = 3), and necrosis of a previous
      substitute (n = 2). Colon interposition represented only 18.5% of all operations
      performed for oesophageal replacement during the same period. The colon was
      selected because of inadequate stomach in 33 cases (55%). Long-segment conduit
      based on the ascending branch of the left colonic artery was the preferred method
      and could be used in 52 patients (86.7%). The colon was placed in the esophageal
      bed in 38 patients (63.3%), substernally in 21 (35%), and subcutaneously in 1.
      Overall operative mortality and morbidity were 8.3% and 65% respectively. Five
      year survival rate was 9% in the 37 patients with esophageal cancer. Seven
      patients (13.5%) required one or more dilatations of the esophagocolonic
      anastomosis. At last follow-up, 34 patients (65.4%) had no difficulty eating.
      Multivariate analysis identified the conduit position in the posterior
      mediastinum as an independent predictor of good functional result (p = 0.0018).
      We conclude that colon interposition for esophageal replacement provides
      satisfactory and durable function; however, early mortality and morbidity are
      substantial.

PMID- 8762262
TI  - [Lymph node excision in cancer of the esophagus].
AB  - This paper analyses the surgical literature devoted to lymph node clearance for
      cancer of the esophagus. Involvement of a small number of lymph nodes by the
      neoplastic process does not preclude long-term survival and even cure. The
      superiority of the 3-field dissection over the 2-field dissection, although
      suggested in the available studies, should be confirmed by a prospective
      randomized study. Extensive lymph node clearance protects many patients from
      local recurrence, and allows to staging of the neoplastic disease and selection
      of those patients who are eligible for adjuvant therapy.

PMID- 8762264
TI  - [Long-term results of vertical banded gastroplasty for morbid obesity].
AB  - Morbid obesity, defined by Body Mass Index (BMI) > 40 kg/m2, has an adverse
      effect on longevity due to a variety of illnesses. Among the numerous techniques
      proposed to control morbid obesity, Vertical Banded Gastroplasty (VBG) changes
      eating behavior. The aim of this study was to analyse the long term results of
      VBG. MATERIAL AND METHODS: Between October 1987 and July 1993, 62 patients, 7 men
      and 55 women, from 20 to 68 years old (Mean: 37.4 +/- 9 ans), underwent VBG for
      morbid obesity. Preoperative mean weight and BMI were 123 +/- 27 kg and 47.3 +/-
      9.8 kg/m2 respectively. Associated diseases were diabetes mellitus (n = 31),
      hypertension (N = 29), hypercholesterolemia (N = 10), hypertriglyceridemia (N =
      21) and joint diseases (N = 18). RESULTS: VBG was performed with a 50 mm marlex
      mesh in 20 cases and with a 47 to 50 mm silastic ring in 42 cases. On patient
      died 3 years later from alcoholic liver cirrhosis and 4 were lost to follow-up.
      With a mean follow-up of 31 months, mean weight and BMI were 86 +/- 21 kg (p <
      0.001) and 32.1 +/- 9.8 kg/m2 (p < 0.001) respectively. Removal of the ring was
      performed in 3 cases, 1 because of neurologic complications and 2 at the
      patient's request. Eight patients (13%) failed to achieve satisfactory weight
      loss. Diabetes mellitus and hypertension resolved in 19 cases,
      hypercholesterolemia resolved in 7 cases and hypertriglyceridemia resolved in 11.
      CONCLUSION: VBG provides significant weight loss which reduces the frequency of
      medical disorders associated with obesity. This result was achieved in 87% of
      patients. The surgical procedure for morbid obesity must be decided conjointly
      with endocrinologist, psychiatrist and surgical staff for good long-term results.

PMID- 8762263
TI  - [Major hepatectomy after intra-arterial chemotherapy for initially unresectable
      liver tumors. Frequency, technical problems, results and indications].
AB  - BACKGROUND: Major hepatectomy after prolonged intra-arterial hepatic chemotherapy
      (IAHC) is extremely rare, because IAHC usually fails to reduce the tumor volume
      sufficiently or obtain a long duration of response, or both, and because it
      impairs hepatic function. The present report was done to study the frequency,
      feasibility and the results of hepatectomy following IAHC. STUDY DESIGN: This
      retrospective study consisted of 14 patients treated with at least six courses of
      IAHC (mean of 17.6, median of 13, range of six to 48 courses) for hepatic tumors:
      colorectal metastases (n = 9), apudoma metastases (n = 4), and hepatoblastoma (n
      = 1). Systemic chemotherapy was associated in eight cases during (n = 5), or
      after (n = 3) IAHC. Initially, multiple hepatic tumors were unresectable in ten
      cases. They eventually became resecable, but were associated with extensive
      extrahepatic sites of involvement in four cases. All patients underwent curative
      major hepatectomy after a careful and specific morphologic and functional hepatic
      assessment. Right portal vein embolization was performed preoperatively upon
      three patients, resulting in 38, 44 and 77 percent hypertrophy of the left lobe
      before hepatectomy. Hepatectomy was also performed upon three patients with
      hepatic arterial thrombosis induced by IAHC, after a careful workup of the
      neoarteriovascularization of the liver. RESULTS: These 14 cases only represented
      5.8 percent of the 239 patients in whom a catheter was inserted for IAHC, and 4.2
      percent of the 335 patients who had hepatectomy for carcinoma. Postoperatively,
      there was no mortality and no clinical hepatic insufficiency. However, ten
      complications occurred in eight patients (three of them resulted in reoperation).
      Histologic examination revealed substantial modifications of the hepatic
      parenchyma because of IAHC. Results concerning survival were very encouraging:
      five of the nine patients with metastases of the colon and rectum are free of
      disease, with a mean follow-up period of 36 months after the beginning of IAHC.
      CONCLUSIONS: The decision to perform a major hepatectomy after prolonged IAHC is
      difficult and must be based on an output morphologic assessment with computed
      tomographic portography and a careful evaluation of functional liver impairment
      because of IAHC (the therapeutic strategy proposed by Makuuchi for hepatectomy in
      patients with cirrhosis, based on indocyanine green clearance and volume to
      resect, is very useful for this purpose). Hepatectomy is technically difficult to
      perform following IAHC because of a flabby parenchyma and unusually high pressure
      in the small central hepatic veins. This draw-back is circumvented by using
      techniques: such as preoperative hypertrophy of the future remaining liver, a
      transparenchymatous approach of vasculobiliary structures, and intermittent
      clamping of the hepatic pedicle or vascular isolation of the liver. Postoperative
      complications occurred more frequently than after major, hepatectomy in other
      clinical settings (p < 0.05). However, as this therapeutic approach greatly
      increases survival, it should not be neglected by clinicians, although
      indications for its use are very rare.

PMID- 8762265
TI  - [Gunshot injuries of the ureter].
AB  - The increased incidence of gunshot injuries of the ureter (GIU) can be explained
      by increased of armed violence in some large cities and by the performance of
      intensive care teams, both in civilian practice and in a context of war. The
      discovery of a GIU, during salvage laparotomy for vascular or visceral lesions is
      no longer exceptional. We report 5 cases of abdomen gunshot wounds with ureteric
      trauma treated between 1987 and 1994 by three surgical teams. The data in the
      literature and the principles of ballistic wounds are analysed. Theses lesions
      are initially misdiagnosed diagnosis in 10 to 20% of cases, as there are no
      specific clinical signs, radiological opacification of urinary tract is rarely
      performed, and septic nature of associated lesions and the ballistic context of
      the trauma guide the treatment of GIU. When the ureteric lesion is short and
      associated lesions are limited, the continuity of the urinary tract can be
      restored after debridement of the extremities by end-to-end anastomosis for the
      upper 2/3 and direct vesical reimplantation or into a psoas bladder for the lower
      1/3. Drainage is ensured either by a bladder catheter or by a double J stent, for
      a minimal duration of 3 weeks. When there is a defect of the upper two-thirds of
      the ureter, mobilization of the kidney and its pedicle or
      transureteroureterostomy may be required. Urinary diversion by nephrostomy or in
      situ ureterostomy is indicated when the haemodynamic state is unstable and the
      associated lesions are very septic or in the presence of multiple lesions.
      Extensive contusion of the ureteric wall must be intubated to prevent fistula
      formation due to necrosis. Nephrectomy should be avoided in these patients with a
      mean age of 27 years.

PMID- 8762266
TI  - [Transfer of space technology to the field of medicine].
AB  - In the context of its technology transfer programme, the European Space Agency
      (ESA) has decided to examine in greater detail the medical applications of space
      technological developments. There are several sectors in which space technologies
      have already been successfully used in biomedical apparatuses, in Europe and in
      North America. The ESA has therefore set up a team designed, among other things,
      to promote exchanges between the space industry and the world of medicine.
      Encouraging results have already been obtained and the medical sector shows an
      increasing interest in this initiative, particularly in the fields of surgery,
      anaesthesia, radiology and telemedicine. The ESA therefore envisages the creation
      of a nonprofit association to extend the actions which it has carried out
      experimentally over the last two years to the whole of Europe and to all medical
      disciplines.

PMID- 8762267
TI  - [Papillary carcinoma developed in the wall of a thyroglossal duct cyst].
AB  - A case of papillary carcinoma arising in the wall of a thyroglossal duct cyst is
      described. This is a rare occurrence (1% of cases). Controversies exist
      concerning its nature (cancer of the thyroid or primary cancer of the
      thyroglossal cyst) and its treatment (Sistrunk's operation alone or combined with
      thyroidectomy).

PMID- 8762268
TI  - [Antineoplastic therapy and perioperative period in oncologic surgery].

PMID- 8762269
TI  - [Cavernous hemangioma of the spleen. Apropos of a case].

PMID- 8762270
TI  - [Fournier's gangrene].

PMID- 8762271
TI  - [Recommendations and medical references 1996].

PMID- 8762272
TI  - [Analysis of texture in medical imaging. Review of the literature].
AB  - This paper presents a review of the applications of texture analysis in medical
      imaging. Many authors take a great interest in this topic (75 papers have been
      published since 1984) and try to elaborate automatic methods for tissue
      characterization. The results are not really convincing and applications are
      often reduced to feasibility studies. This failure is due to the empirical
      approach to the problem: the first studies were performed on ultrasound images,
      in which visual texture is very present, but no data standardization is available
      with this imaging modality. A more rational approach should provide better
      results. For each organ or tissue, it is necessary to find the appropriate source
      and texture analysis method. This difficult task requires reflection concerning
      the interactions between tissues and imaging sources, to define judicious
      structuring elements. These structuring elements should facilitate the choice of
      the best texture analysis method, for the particular application. Considerable
      methodological progress has yet to be made, after which texture analysis should
      be a useful and efficient tool for clinical use.

PMID- 8762273
TI  - [Glossary of terms used by radiologists in image processing].
AB  - We give the definition of 166 words used in image processing. Adaptivity,
      aliazing, analog-digital converter, analysis, approximation, arc, artifact,
      artificial intelligence, attribute, autocorrelation, bandwidth, boundary,
      brightness, calibration, class, classification, classify, centre, cluster,
      coding, color, compression, contrast, connectivity, convolution, correlation,
      data base, decision, decomposition, deconvolution, deduction, descriptor,
      detection, digitization, dilation, discontinuity, discretization, discrimination,
      disparity, display, distance, distorsion, distribution dynamic, edge, energy,
      enhancement, entropy, erosion, estimation, event, extrapolation, feature, file,
      filter, filter floaters, fitting, Fourier transform, frequency, fusion, fuzzy,
      Gaussian, gradient, graph, gray level, group, growing, histogram, Hough
      transform, Houndsfield, image, impulse response, inertia, intensity,
      interpolation, interpretation, invariance, isotropy, iterative, JPEG, knowledge
      base, label, laplacian, learning, least squares, likelihood, matching, Markov
      field, mask, matching, mathematical morphology, merge (to), MIP, median,
      minimization, model, moire, moment, MPEG, neural network, neuron, node, noise,
      norm, normal, operator, optical system, optimization, orthogonal, parametric,
      pattern recognition, periodicity, photometry, pixel, polygon, polynomial,
      prediction, pulsation, pyramidal, quantization, raster, reconstruction,
      recursive, region, rendering, representation space, resolution, restoration,
      robustness, ROC, thinning, transform, sampling, saturation, scene analysis,
      segmentation, separable function, sequential, smoothing, spline, split (to),
      shape, threshold, tree, signal, speckle, spectrum, spline, stationarity,
      statistical, stochastic, structuring element, support, syntaxic, synthesis,
      texture, truncation, variance, vision, voxel, windowing.

PMID- 8762274
TI  - [Intrathoracic goiters. 62 surgically treated patients].
AB  - OBJECTIVES: Intrathoracic goitres present as tumors of the upper mediastinum.
      Malignancy is uncommon, but sudden or progressive development often leads to
      compression of the trachea. We report here our experience with surgical exeresis.
      METHODS: From 1980 to 1995, we operated 62 patients with intrathoracic goitre.
      There were 23 men and 39 women (mean age 63 years). The main manifestations
      leading to diagnosis were dyspnea (n = 20; 32%) and identification of a
      mediastinal formation on routine chest x-rays (n = 19; 30%). RESULTS:
      Antevascular goitre was seen in 24 patients (39%) and retrovascular goitre in 38
      (61%). The retrovascular goitres were located anteriorly and laterally to the
      trachea in 21 patients (34%) and posteriorly in 17 (27%). Simple cervicotomy was
      used in 57 patients (92%). Manubriotomy (n = 1) and total sternotomy (n = 4) were
      also required. All intrathoracic goitres removed were benign. Post-operative
      mortality was nul and morbidity was 11%: 2 cases of hypocalcemia and 2
      tracheomalacias including 1 with recurrent nerve palsy and one with hematoma and
      pulmonary infection. CONCLUSION: Surgical exeresis of intrathoracic goitre is
      essentially required in case of respiratory distress due to compression of the
      trachea. Morbidity is low with simple cervicotomy.

PMID- 8762275
TI  - [Community-acquired pneumonia in children: importance of Mycoplasma pneumoniae
      infections and efficacy of antibiotics].
AB  - OBJECTIVES: Define a therapeutic management schema adapted to children with
      community-acquired pneumonia. METHODS: A prospective survey was conducted in 104
      children over 18 months of age with community-acquired pneumonia. The pathogen
      was isolated in 85% of the cases. RESULTS: Viral infection alone was proven in 30
      children (respiratory syncytial virus in 10). Pneumococci pneumonia was found in
      12 patients; the isolated strains were sensitive to penicillin. Apyrexia was
      obtained in 11/12 cases with amoxicillin. Mycoplasma infections occurred in 42%
      of the cases (41 alone and in association with pneumococci in 2 cases).
      Pneumococci and mycoplasma infections could not be differentiated with standard
      radiography and laboratory tests. Initial treatment with beta lactamines was
      always unsuccessful in children with mycoplasma infections. Apyrexia was achieved
      when antibiotics were changed to macrolides. CONCLUSION: Since lower respiratory
      tract infections due to pneumococci are much more severe than those due to
      mycoplasma, beta lactamines should be given as first intention treatment for
      children over 18 months with pneumonia. Macrolides should be given in case of
      failure because mycoplasma would then be the most probable infectious agent.

PMID- 8762276
TI  - [Lipoprotein glomerulopathy: a new French case with recurrence on the
      transplant].
AB  - Lipoprotein glomerulopathy is defined by the presence of lipidic deposits in the
      capillary lumen giving them a dialted and microaneurysmal aspect and the presence
      of quantitative and/or qualitative alterations of plasma apolipoprotein E. We
      describe here the long-term follow-up of a young female patient who presented
      with corticoresistant nephrotic syndrome in 1979 and progressed to chronic renal
      failure requiring dialysis in 1990. The three renal biopsies performed during the
      follow-up showed markedly enlarged capillary loops due to intra-luminal
      fibrinolipidic material deposition forming true intracapillary thrombi. She
      received a cadaver renal transplant in 1993. One year after transplantation,
      nephrotic syndrome reappeared and graft biopsy showed recurrence of the initial
      glomerular disease on the transplant. The plasma lipid profile showed
      hypercholesterolemia, hypertriglyceridemia, and elevated plasma ApoE levels with
      an abnormal Apo E phenotype. Our case report is a new typical case of lipoprotein
      glomerulopathy with recurrence of the initial disease on the renal allograft.

PMID- 8762277
TI  - Breast abscess with lethal septicemia due to Pseudomonas aeruginosa in a patient
      with AIDS.
AB  - OBJECTIVE: The incidence of Pseudomonas aeruginosa in HIV-infected patients has
      increased over the last years. We describe a case of pseudomonal breast abscess
      complicated with fatal septicemia in an AIDS patient. CASE REPORT: A 21-year-old
      woman was admitted for fever, chills, nausea, vomiting and pain in the breast.
      She had a swelling in the right breast of 3 days duration. HIV infection had been
      confirmed 6 years earlier. CD4 count was 2/mm3. Surgical drainage produced a blue
      green purulent discharge which grew Pseudomonas aeruginosa on culture. Despite
      cloxacilin, then ceftazidime and amikacin, initial improvement was followed 2
      weeks later by nodular pulmonary infiltration with cavitation. P. aeruginosa was
      recovered from sputum and blood cultures, but stepwise resistance developed and
      the patient died 3 months after admission. DISCUSSION: Breast abscesses are
      infrequent in nonlactating women. P. aeruginosa is rarely involved, even in HIV
      patients. Due to the risk of resistance, prompt administration of appropriate
      antibiotics is required.

PMID- 8762278
TI  - [Closure of bronchopleural fistula by video-assisted mediastinal surgery after
      pneumonectomy].
AB  - Disruption of a mainstream bronchus is a rare but dreaded complication of
      pneumonectomy. When the bronchial tump measures at least 15 mm, the conventional
      therapeutic strategy is to drain the pleural cavity followed by closure of the
      fistula via trans-mediastinal sternotomy. After an experimental study on cadavers
      to test the technical feasibility of main bronchus closure via a cervical
      approach using a video-mediastinoscope, we used video-assisted mediastinal
      surgery successfully in a patient with a left main bronchus fistula.

PMID- 8762279
TI  - [Pleuropulmonary manifestations of rheumatoid arthritis].
AB  - Respiratory complications are important morbidity and mortality factors in
      rheumatoid arthritis. Either the disease itself, secondary effects of necessary
      drugs, or infections favored by the relative immunosuppression resulting from the
      disease and therapy can affect all the respiratory structures: airways, lung
      parenchyma, vessels, chest wall, respiratory muscles. The combined efforts of
      rheumatologists and pneumologists are required for correct management.

PMID- 8762280
TI  - [Delivery of women with cicatricial uterus].
AB  - Cesarean section rate has risen dramatically, particularly in the U.S., over the
      past 20 years, with results on maternal and perinatal mortality or morbidity and
      increase of delivery cost. To curb this inflation, trial of labor after cesarean
      section is proposed. Trial of labor often involves use of oxytocics. Regional
      analgesia is indicated for this high risk delivery. There are few absolute contra
      indications to trial of labor and each case has to be analysed separately.
      Induction of labor leads to several advantages. The repeat cesarean section rate
      decreases significantly; this high risk delivery can take place during daytime
      with complete obsetetrical, anaesthetic and pediatric staff. The use of
      medication such as vaginal prostaglandins or mifepristone can also help lower
      this rate. X-ray pelvimetry must no longer be the major criterion for choosing
      the mode of delivery. Normality of labour must be judged according to previous
      vaginal delivery or not. Revision of uterine scar remains important for the
      diagnosis of dehiscence or rupture. This exploration should only be done if
      symptoms appear.

PMID- 8762281
TI  - [Arterial injuries in leg fractures].

PMID- 8762282
TI  - [Sale of devices for intravenous injection to drug abusers. A survey of
      pharmacies in Nice 1995].

PMID- 8762283
TI  - [Acute erythroblastopenia in children caused by parvovirus B 19].

PMID- 8762284
TI  - [Mononucleosis syndrome in dengue].

PMID- 8762285
TI  - [Hypertriglyceridemia caused by interferon-alpha].

PMID- 8762286
TI  - Loss of libido in a 'happily married' man.

PMID- 8762287
TI  - Progress in the treatment of pain.

PMID- 8762288
TI  - Face to face with the examiners.

PMID- 8762289
TI  - Assessing blood flow in practice.

PMID- 8762290
TI  - Preventing and treating osteoporosis.

PMID- 8762291
TI  - Treatment options in endometriosis.

PMID- 8762292
TI  - Chickenpox in pregnancy: how dangerous?

PMID- 8762293
TI  - Chlamydia: testing for the silent threat to fertility.

PMID- 8762294
TI  - When is hypertension a cause for concern?

PMID- 8762295
TI  - Receptive field structure in the primate retina.
AB  - This review summarizes recent work relevant to receptive field structure of cells
      of the parvocellular (PC) and (MC) magnocellular pathways in the primate. In the
      PC-pathway, recent data suggest that different color- and cone-opponent ganglion
      cells make up specific anatomical classes with specific cone connectivities and
      bipolar cell input. For example, blue-on ganglion cells have been identified
      anatomically as the small bistratified ganglion cell class. For the midget
      ganglion cells, which appear to be red-green opponent, there seems to be only one
      mosaic for red and green on-center and one for red and green off-center cells.
      This mixture of cell type within a retinal cell mosaic is unusual, as is the fact
      that dendritic trees of neighboring midget cells do not overlap. Physiologically,
      all PC-cells lack a contrast gain control mechanism and show a high degree of
      spatial and temporal linearity of their responses. In the magnocellular pathway,
      on- and off-center cells, corresponding to parasol cells with dendritic trees
      ramifying in the inner and outer sublaminae of the inner plexiform layer, show
      properties familiar from studies of cat ganglion cells, e.g. a contrast gain
      control is present. However, a chromatic input to the receptive field surround
      gives their responses an additional order of complexity.

PMID- 8762296
TI  - Color and luminance vision in human amblyopia: shifts in isoluminance, contrast
      sensitivity losses, and positional deficits.
AB  - The deficits for contrast detection and positional accuracy were compared for
      chromatic and luminance mechanisms within a group of strabismic and anisometropic
      amblyopes. We found that the isoluminant point was shifted towards red in the
      amblyopic compared to the fellow normal eye. This was not accounted for by
      eccentric fixation by the amblyopic eye. Contrast sensitivity deficits were
      similar for luminance and color stimuli in normal and amblyopic visual systems.
      In the majority of our amblyopic subjects, however, the deficits in positional
      acuity were greater for the chromatic than the luminance stimuli.

PMID- 8762297
TI  - Cyclopean motion perception produced by oscillations of size, disparity and
      location.
AB  - For cyclopean and monocularly-visible targets we measured psychophysical
      thresholds for perceptions produced by the following three stimuli: oscillations
      of disparity (DO), oscillations of size (SO) and oscillatory motion within the
      frontoparallel plane (FPO). RESULTS: thresholds for motion in depth perception
      produced by DO were similar for cyclopean and non-cyclopean targets over the
      entire 0.25-8 Hz frequency range investigated. Thresholds for perceiving motion
      in depth produced by SO were considerably (up to 2.5 times) higher for cyclopean
      targets than for monocularly-visible targets, as were thresholds for perceiving
      size oscillations. For both cyclopean and monocularly-visible target the
      perception of motion in depth could be canceled by pitting DO vs SO. Thresholds
      for perceiving FPO were similar to DO thresholds for the monocularly-visible
      target, but for the cyclopean targets FPO thresholds rose more steeply than DO
      thresholds for oscillation frequencies above 1 Hz. CONCLUSIONS: (1) for our
      subjects, the effective binocular stimulus for motion in depth perception is a
      rate of change of disparity; an interocular velocity difference is significant
      only to the extent that it produces a rate of change of disparity. (2) The
      sensations of motion in depth produced by DO and SO are qualitatively identical.
      (3) Neural signals produced by DO and SO converge onto a single neural mechanism
      that signals motion in depth.

PMID- 8762298
TI  - Speed estimates from grating patches are not contrast-normalized.
AB  - We have previously shown that the perceived speed of a moving grating depends
      upon its contrast, with lower-contrast patterns appearing to move more slowly
      than otherwise identical higher-contrast patterns. To explain this finding while
      remaining consistent with the findings of McKee, Silverman and Nakayama [(1986)
      Vision Research, 26, 609-619], we proposed that this misperception might arise
      from a modified version of the contrast-normalization procedure, envisaged by
      Adelson and Bergen [(1986) The extraction of spatio-temporal energy in human and
      machine vision (pp. 135-139). Charleston, S.C.: IEEE Computer Society] as a
      necessary second stage of motion-energy models of human motion processing.
      Specifically, our previous results might be explained if the two gratings to be
      compared interfered with each other's normalization. To test this hypothesis we
      performed two experiments. Experiment 1 demonstrates that the contrast effects
      persist even when two grating patches to be compared are presented up to 5 sec
      apart so that they would not be expected to bias each other's normalization.
      Experiment 2 shows that the contrast effects are unchanged when the two grating
      patches are surrounded by a range of patterns whose contrast would be expected to
      interfere with any normalization process. These two results allow the rejection
      of the contrast-normalized motion-energy hypothesis as an explanation of human
      speed perception. We discuss the consequences of these results on models of speed
      processing in the human visual system.

PMID- 8762299
TI  - Multiple matching of features in simple stereograms.
AB  - Simple stereograms are used to show that the binocular matching of closely spaced
      vertical lines can be changed by horizontally connecting some of the vertical
      lines. The matching that is seen can be gradually changed by incremental
      modifications to simple visual quantities like the luminance contrast of a local
      region, or the density of the connecting horizontal lines. For some values of
      these visual quantities the depth seen is unstable which suggests that the
      mechanisms responsible for resolving matching ambiguities might be intrinsically
      dynamic. These changes in binocular matching can also be used to show a
      hysteresis-like effect in stereopsis. Many of the constraints like ordering,
      cohesivity, and uniqueness often used in algorithms for resolving ambiguities are
      perhaps too limiting to allow either such dynamics or the processing of
      transparent or partially occluded surfaces.

PMID- 8762300
TI  - Perceived motion in depth.
AB  - We examine how various sources of information contribute to the percept of motion
      in depth. Subjects were presented with targets moving in depth, and were asked to
      judge their velocities and final positions. On each presentation, the target's
      position relative to the two eyes (target vergence), the size of the target's
      retinal image and the difference in this image's position relative to that of the
      background in the two eyes (relative disparity), each either changed as they
      normally would for a target moving at a fixed speed towards the observer, or did
      not change at all. Subjects' judgements for various such combinations show that
      all three sources of information influence both the perceived velocity of motion
      in depth and the final perceived position, but in different ways. This is not too
      surprising, because the assumptions that the use of each source of information
      are based on, are different for the two tasks. We propose that the way the
      different sources are combined is governed by the likelihood of the assumptions,
      that are required to use that information, being true under the given
      circumstances.

PMID- 8762301
TI  - The effect of dark and equiluminant occlusion on the interocular transfer of
      visual aftereffects.
AB  - Lehmkuhle and Fox [(1976) Vision Research, 16, 428-430] reported that interocular
      transfer (IOT) of a translational motion aftereffect (MAE) was greater if the non
      adapting eye viewed an equiluminant field than if it viewed a dark field. They
      recommended equiluminant occlusion of the non-adapted eye when measuring IOT of
      aftereffects. We tested this proposal in three experiments. First, we assessed
      IOT with equiluminant and dark occlusion for three different classes of
      aftereffects. Although transfer was greater with equiluminant occlusion for the
      translational MAE, there was no significant difference in the amount of transfer
      for the tilt aftereffect or the contrast threshold elevation effect. Second, we
      tested the hypothesis that spuriously large IOT could be the result of an
      aftereffect from tracking eye movements in the non-adapting eye. When potential
      tracking movements were reduced by using rotating spokes, a rotating spiral or
      contracting concentric circles, there was a corresponding reduction in the
      occlusion-dependent transfer. Third, we found that luminance shifts had no
      influence on the amount of transfer when all contours were eliminated from the
      non-adapting eye. We conclude that the type of occlusion used for measuring IOT
      of the translational MAE is important only when visible contours in the non
      adapting eye contribute to the adapting process.

PMID- 8762302
TI  - Intrinsic uncertainty and integration efficiency in bisection acuity.
AB  - A spatial perturbation paradigm was used to determine equivalent intrinsic
      uncertainty and spatial integration efficiency in bisection. Specifically, three
      line bisection thresholds were measured in the fovea of four normal observers
      with stimulus lines comprised of discrete dark dots distributed randomly around
      the mean line position according to a Gaussian function. The standard deviation
      of the Gaussian distribution (sigma e), the number (N), and the strength (C) of
      the dots as well as line separation were varied. Bisection thresholds were
      modeled by an ideal integrator, from which the magnitude of equivalent internal
      uncertainty (sigma i), the equivalent effective number of dots (k), and
      equivalent integration efficiency (k/N) were quantified. At the 2 min arc
      separation, sigma i decreases (down to a few sec arc) as N and/or C increases.
      The effects of both N and C can be accounted for by the stimulus visibility (V,
      in multiples of detection threshold). At the 16 min arc separation, sigma i is
      independent of N, C, or V, and is about 1 min arc. The two different forms of
      sigma i indicate that bisection judgments are limited by at least two separate
      sources of limiting noise, consistent with the hypothesis of two separate
      mechanisms (i.e. spatial filters and local signs). A visibility dependent sigma i
      at the 2 min arc separation can be explained on the basis of contrast sensitive
      spatial filter mechanisms. A fixed sigma i at the 16 min arc separation indicates
      a genuine positional uncertainty, consistent with local-sign mechanisms.
      Interestingly, equivalent integration efficiency (k/N) is very similar at the two
      line separations. k/N is critically dependent on, and proportional to C,
      indicating a common limitation in a detection mechanism.

PMID- 8762303
TI  - Modification of the Filehne illusion by conditioning visual stimuli.
AB  - During smooth pursuit eye movements made across a stationary background an
      illusory motion of the background is perceived (Filehne illusion). The present
      study was undertaken in order to test if the Filehne illusion can be influenced
      by information unrelated to the retinal image slip prevailing and to the eye
      movement being executed. The Filehne illusion was measured in eight subjects by
      determining the amount of external background motion required to compensate for
      the illusory background motion induced by 12 deg/sec rightward smooth pursuit.
      Using a two-alternative forced-choice method, test trials, which yielded the
      estimate of the Filehne illusion, were randomly interleaved with conditioning
      trials, in which high retinal image slip was created by background stimuli moving
      at a constant horizontal velocity. There was a highly reproducible monotic
      relationship between the size and direction of the Filehne illusion and the
      velocity of the background stimulus in the conditioning trials with the following
      extremes: large Filehne illusions with illusory motion to the right occurred for
      conditioning stimuli moving to the left, i.e. opposite to the direction of eye
      movement in the test trials, while conversely, conditioning stimuli moving to the
      right yielded Filehne illusions close to zero. Additional controls suggest that
      passive motion aftereffects are unlikely to account for the modulation of the
      Filehne illusion by the conditioning stimulus. We hypothesize that this
      modification might reflect the dynamic character of the networks elaborating
      spatial constancy.

PMID- 8762304
TI  - Stationary and pursuit visual fixation share similar behavior.
AB  - Stationary and pursuit fixation may involve different fixation mechanisms that
      are reflected by differences in saccadic reaction times (SRTs). Gap,
      Simultaneous, and Overlap interval paradigms provided three distinct SRT ranges
      for comparisons between these two viewing conditions. SRTs following pursuit
      fixation were longer than following stationary fixation, but were similarly
      affected by the interval paradigms. The SRT increase with smooth pursuit was
      largely explained by additional demands for programming oblique saccades. The
      paradigm dependent SRT relationships also persisted after timing cues were
      minimized. These results indicate that stationary and pursuit fixation have
      similar responses to different fixation paradigms and do not implicate the
      existence of multiple fixation processes.

PMID- 8762305
TI  - Components of visual acuity loss in strabismus.
AB  - Strabismus, the misalignment of the visual axis of one eye relative to that of
      the other eye, reduces visual acuity in the affected eye. Several processes
      contributing to that loss are: amblyopia, which results in a chronic acuity loss
      whether or not the fellow eye is viewing; strabismic deviation, which shifts the
      image of an acuity target onto more peripheral, and therefore less acute, retina
      when the fellow eye fixates; interocular suppression and binocular masking, which
      reduce visibility in the strabismic eye due to neural influences from the other
      eye. We measured the losses due to these processes in nine small-angle strabismic
      subjects. Amblyopia reduced acuity by a median of 34% relative to its value in
      subjects with normal binocular vision, and strabismic deviation produced a loss
      of 44%. Suppression and masking together reduced acuity by 20%, and therefore had
      substantially less effect than the other factors.

PMID- 8762306
TI  - Medial meatal fibrosis: current approach.
AB  - Medial meatal fibrosis is a rare entity which is linked to inflammatory and
      traumatic factors. This pathology significantly benefits from surgical
      management. Criteria for achieving successful results are strict and concern the
      complete removal of the fibrous tissue and covering of the bony canal with skin
      graft. The aim of this paper is to present our experience with this rare
      pathology and to discuss current approaches.

PMID- 8762307
TI  - Day-stay myringoplasty.
AB  - Grafting of the tympanic membrane (myringoplasty) has traditionally been
      performed as an in-patient procedure in the UK. We have performed day-stay
      myringoplasty on 21 consecutive patients (15 adults and six children) under
      general anaesthesia using an underlay temporalis fascia graft. In 18 cases there
      was complete healing of the tympanic membrane and in three cases the patients
      developed perforations at four weeks. This success rate is consistent with
      previously reported studies. All patients were discharged on the day of admission
      with no major complications. We have compared the results with a group of
      patients having the same operation as an in-patient and have concluded that day
      stay myringoplasty under general anaesthesia is as safe and effective as in
      patient surgery for the majority of patients.

PMID- 8762308
TI  - An animal model for training in endoscopic nasal and sinus surgery.
AB  - An animal model has been devised to allow trainees in nasal and sinus endoscopy
      to develop basic instrument handling and psychomotor skills, without risk to
      patients. The sheep's head obtained from the abattoir was modified slightly to
      simulate more closely the human situation. The model permits nasendoscopy,
      foreign body removal, septoplasty, turbinate reduction, frontal and maxillary
      sinoscopy, antrostomy and an epistaxis exercise. To date the tissues have been
      used freshly thawed, and must be used on the day of preparation.

PMID- 8762309
TI  - Trans-nasal endoscopic holmium: YAG laser correction of choanal atresia.
AB  - Five patients with choanal atresia were treated, using a trans-nasal endoscopic
      Holmium:YAG laser. The age of patients ranged from 15 months to 53 years. The
      nasal endoscope provides excellent visualization. The advantage of the
      Holmium:YAG laser is its fibre-optic delivery, allowing the laser to be hand
      held, giving greater precision. Good nasal airways were achieved in four out of
      five cases with a single treatment. The procedure was found to be safe, quick,
      with minimal morbidity and a shorter in-patient stay.

PMID- 8762310
TI  - Endoscopic control of posterior epistaxis.
AB  - Control of bleeding vessels by suction cautery under endoscopic vision was used
      on 38 patients suffering from posterior epistaxis. Twelve patients also required
      the insertion of nasal tampons at the end of the cautery procedure. Eight
      patients, six of them hypertensive, had recurrent epistaxis post-operatively.
      Five patients needed further cautery in order to control the bleeding. Three
      patients required temporary balloon tamponade, and a single patient had internal
      maxillary ligation. Temporary palatal numbness in three patients was the only
      post-operative complication. Otherwise, the technique has the potential
      advantages of simplicity, safety, effectiveness and simplified post-operative
      care.

PMID- 8762311
TI  - Acute laryngeal trauma: a comparison between peace time and war injuries.
AB  - Thirty-six patients with acute laryngeal trauma are presented. Sixteen patients
      had peace-time and 20 had war injuries. Peace-time injuries were mostly due to
      car accidents, violence and suicide using a knife, whereas the war injuries were
      caused by shell and mine fragments. Nine patients were treated conservatively
      (eight peace-time and one war-time) and 27 by surgery (eight peace-time and 19
      war-time). Surgical experience showed that acute laryngeal trauma must be treated
      within the first 24 hours after injury. Primary treatment must be a definite one.
      In that way complications and uncontrolled healing can be successfully avoided.

PMID- 8762312
TI  - Expression of Ki-67 antigen and proliferative cell nuclear antigen in benign and
      malignant epithelial lesions of the larynx.
AB  - In an attempt to analyse the proliferative activity in benign and malignant
      laryngeal epithelial lesions, and to determine the relationship to their
      histologic grade, we studied the expression of proliferative cell nuclear antigen
      (PCNA) and Ki-67 antigen on 20 squamous carcinomas, and on 30 biopsies of
      epithelial hyperplasia categorized according to the Kambic-Lenart classification
      into simple, abnormal, and atypical hyperplasias. In simple hyperplasia, both
      antibodies stained the nuclei of the occasional cells in the basal layer. In
      abnormal hyperplasia (mild dyplasia), positive cells occupied up to a third, and
      in atypical hyperplasia (moderate and severe dysplasia) they occupied from two
      thirds to the entire epithelial thickness. In squamous carcinoma, we have found a
      statistically significant correlation between its grade and the percentage of Ki
      67-(p < 0.01) and PCNA-(p < 0.00001) positive cells. Our results suggest that the
      proliferative fraction progressively increases with the degree of epithelial
      hyperplasia and the grade of carcinoma. We conclude that the patterns of
      immunoreactivity to PCNA and Ki-67 antigen correspond to the histologic grade of
      both benign and malignant epithelial lesions of the larynx. This method should be
      regarded as a useful adjunct to traditional histological techniques allowing more
      objective grading of benign and malignant epithelial lesions.

PMID- 8762313
TI  - Post-tonsillectomy pain with selective diathermy haemostasis.
AB  - A prospective randomized study was carried out to assess the post-tonsillectomy
      morbidity of the selective diathermy technique as opposed to the ligation
      technique. One hundred and five patients had one tonsillar fossa haemostasis
      secured by unipolar diathermy and the opposite side by ligation technique. There
      was significantly less pharyngeal pain on the diathermy side in the first post
      operative day. However, there was no significant difference between the two
      sides, both in pharyngeal discomfort and otalgia for the rest of the post
      operative period. There was no difference in the incidence of haemorrhage between
      the two techniques.

PMID- 8762314
TI  - Inhibition of head and neck metastatic and/or recurrent cancer by local
      administration of multi-cytokine inducer OK-432.
AB  - The multi-cytokine inducer OK-432 is a pulverized preparation of the low
      virulence SU strain of Streptococcus pyogenes of human origin. A reduction of the
      tumour mass in the OK-432-injected areas was observed in 11 out of 13 patients
      with metastatic and/or recurrent head and neck cancer. Complete response (CR),
      partial response (PR) and minor response (MR) were noted in six, three and two
      cases respectively. OK-432 local administration therapy could create a new
      strategy for cancer therapy.

PMID- 8762315
TI  - Tympanic thermometry and minor ear surgery.
AB  - Infra-red tympanic thermometry is a relatively new technique for measuring body
      temperature which requires the minimum of co-operation and is quick and easy to
      use. It is therefore ideal for use in children. Its use is becoming more
      widespread and as it is theoretically possible that minor ear surgery may
      interfere with function its reliability in these patients may be in question.
      Twenty-two children (mean age 5.3 years) who underwent myringotomy +/- grommet
      insertion had the tympanic temperature of each ear measured immediately before,
      and 15 minutes after, surgery on the recovery ward. No difference was found
      between the pre- and post-operative temperatures (mean difference--0.1 degree C,
      p > 0.1, paired t-test, hypothesized difference of 0). This thermometer appears
      to be a reliable way of monitoring body temperature on a paediatric ENT recovery
      ward in patients who have undergone minor ear surgery.

PMID- 8762316
TI  - Meatoplasty in Marfan syndrome.
AB  - Marfan syndrome (MS) is a rare connective tissue disorder, uncommon in otological
      practice. Ear surgery in MS has not been previously reported. An identical
      complication of meatoplasty developed in two patients with MS after modified
      radical mastoidectomy and meatoplasty for chronic otitis media. Both cases
      presented post-operatively with an external auditory canal narrowing when the
      walls of the initial meatoplasty in both cases collapsed. It is proposed that
      this occurred because of the inherent structural abnormality of the cartilage in
      Marfan syndrome. A simple technique of revision meatoplasty is described that
      resulted in successful management of these cases.

PMID- 8762317
TI  - Early diagnosis of Wegener's granulomatosis presenting with facial nerve palsy.
AB  - Wegener's granulomatosis is a multi-system disease characterized by granuloma
      formation and a necrotizing vasculitis. It classically presents with involvement
      of the upper and lower respiratory and renal systems. However locoregional
      disease is common and may include otological manifestations. Facial nerve palsy
      has been reported during the course of the disease process but it is extremely
      rare for it to be the presenting feature. Previously reported cases have involved
      a protracted diagnostic process including exploratory tympanotomy, mastoidectomy
      and facial nerve decompression. We report a case of Wegener's granulomatosis
      which presented with a facial nerve palsy. An early diagnosis was achieved by
      measurement of the erythrocyte sedimentation rate (ESR), followed by serological
      assay of cytoplasmic anti-neutrophil cytoplasmic antibody (cANCA). Histological
      examination of nasal mucosal biopsies confirmed granuloma formation consistent
      with a diagnosis of Wegener's granulomatosis. This allowed early treatment with
      immunosuppressive therapy and avoided unnecessary and potentially hazardous
      middle ear surgery.

PMID- 8762318
TI  - Vestibular nerve dysfunction and decompression in Engelmann's disease.
AB  - Vestibular nerve dysfunction as the major neuro-otological symptom in one of the
      osteopetrosis group of bone disorders is unusual. We describe a patient with
      Engelmann's disease who presented in this manner and who benefited from an eighth
      nerve decompression procedure. Surgical decompression of the internal auditory
      meatus to relieve vertigo has to our knowledge not been previously reported in
      this condition.

PMID- 8762319
TI  - Drug induced otalgia due to mesalazine and sulphasalazine.
AB  - A case of left otalgia in a patient suffering from longstanding ulcerative
      colitis is reported. The patient was treated for an exacerbation of his disease
      with courses of mesalazine and sulphasalazine during which time he developed
      otalgia. The otalgia disappeared with cessation of the drugs. It is concluded
      that in the absence of any other head and neck cause that the otalgia was a
      complication of the drug therapy.

PMID- 8762320
TI  - Solitary fibrous tumour arising in the nasal cavity: report of a case.
AB  - The nasal and the paranasal sinuses are a rare site for solitary fibrous tumours.
      There have been no previously reported cases in the English literature, with
      eight cases in the world literature (Witkin and Rosai, 1991; Zuckerberg et al.,
      1991). We present a case of a solitary fibrous tumour arising in the nasal cavity
      and review the previous reports.

PMID- 8762321
TI  - Mucormycosis of the sphenoid sinus in an otherwise healthy patient. Case report
      and literature review.
AB  - Paranasal and rhinocerebral mucormycosis refers to uncommon opportunistic fungal
      infections, reported to occur especially in association with diabetic acidosis
      (the most common), immunosuppressive therapy, malignancy, or other chronic
      debilitating disorders. However, patients who have no underlying disease have
      occasionally been affected. According to the literature reviewed, only 13 well
      documented cases without any predisposing factor have been previously reported.
      We describe a unique case of sphenoidal mucormycosis in an otherwise healthy
      individual, and the first patient to present with headache as the only symptom.
      We emphasize the importance of a high index of suspicion for early diagnosis and
      prompt management.

PMID- 8762322
TI  - Benign fibrous histiocytoma of the larynx: presentation of a case and review of
      the literature.
AB  - A case of a benign histiocytoma of the larynx in a 39-year-old man is presented.
      Laryngeal fibrous histiocytoma is extremely rare. Its pathology is described
      including arguments for benignity. The literature is reviewed and management is
      discussed.

PMID- 8762323
TI  - Hoarseness as the initial manifestation of systemic lupus erythematosus.
AB  - A 51-year-old woman complained of hoarseness of two years duration. The patient's
      past medical history was significant for autoimmunological hepatitis and
      arthritis for which she had not received treatment. Laryngoscopy and laryngeal
      stroboscopy revealed 'bamboo joint-like nodules' on both true vocal folds. These
      nodules resembled rheumatoid nodules and were suggestive of a collagen disease.
      Previous reports have documented that the treatment for such conditions related
      to collagen diseases is surgical resection. However, we initially attempted to
      treat the laryngeal lesions systemically with prednisolone. The hoarseness and
      the bamboo-like nodules disappeared six months after the treatment. Furthermore,
      the liver function test returned to normal and arthritis completely resolved.
      Based on our patient's response to this treatment, we diagnosed atypical-SLE and
      a lupus laryngitis. This case suggests that studies of the larynx may be helpful
      in the early diagnosis of collagan diseases and that such conditions may respond
      to systemic treatment.

PMID- 8762324
TI  - Giant hamartoma of the oropharynx.
AB  - Giant polypoidal hamartomas of the pharynx and oesophagus are rare benign tumours
      of unknown origin, exceptionally arising from the oropharynx. We report the case
      of a 74-year-old man who developed sudden nausea and a foreign body sensation.
      Shortly afterwards he regurgitated a 25 x 3 x 1.5 cm pedunculated fleshy mass,
      still attached to the inside of his thorat. The patient was anaesthetised, the
      mass traced to the right tonsillar fossa and adjacent oropharyngeal wall. The
      pedicle was clamped and the lesion excised. Histology was consistent with a giant
      oropharyngeal hamartoma. We discuss the pathogenesis and potential complications
      of this condition. The literature is reviewed.

PMID- 8762325
TI  - Retropharyngeal abscess-an unusual complication of anorexia nervosa.
AB  - An unusual case of an adult female with anorexia nervosa, who developed a
      retropharyngeal abscess, is presented. This case is reported both because of the
      paucity of reports on retropharyngeal abscess and because of the dramatic unusual
      aetiology.

PMID- 8762326
TI  - Parapharyngeal vagal neurilemmoma extending to the jugular foramen.
AB  - A large vagal neurilemmoma in a 33-year-old man is reported. He complained of
      slowly progressive palsy of the tongue on the left side. Weakness of soft palate
      movement was also noted. Magnetic resonance imaging (MRI) revealed a tumour in
      the left parapharyngeal space with partial extension to the posterior cranial
      fossa through the jugular foramen. Carotid angiography revealed avascularity of
      the tumour and anterior shift of the left internal carotid artery. The venous
      phase showed no blood flow in the internal jugular vein. The tumour was
      successfully extirpated via a transmandibular transpterygoid approach. Although
      vagus nerve dysfunction was not observed pre-operatively, the tumour was
      identified as a neurilemmoma arising from the vagus nerve. The surgical approach
      should be selected according to the lesion in individual patients. Since
      neurilemmoma is benign in nature, minimal post-operative sequelae should be
      expected.

PMID- 8762327
TI  - Metastatic papillary thyroid carcinoma presenting as a typical branchial cyst.
AB  - Two cases of papillary thryoid carcinoma presenting as a cystic lateral neck mass
      are reported. This tumour characteristically presents in patients under 40-years
      old and in the presence of an occult primary tumour may mimic a branchial cyst.
      In such cases simple aspiration of the cyst will produce a chocolate-brown serous
      fluid which excludes the diagnosis of a branchial cyst and is characteristic of
      papillary thyroid carcinoma. Cytological examination of the fluid has a high
      degree of sensitivity and specificity in the diagnosis of thyroid malignancy and
      should avoid delay in diagnosis and unnecessary surgical exploration prior to
      definitive treatment.

PMID- 8762328
TI  - Epithelial-myoepithelial carcinoma of the parotid gland. An unusual cause of ear
      canal stenosis.
AB  - Epithelial-myoepithelial carcinoma (EMC) accounts for approximately one per cent
      of salivary gland tumours. This tumour is gaining wider recognition following
      inclusion into the WHO histological classification of salivary gland tumours in
      1990. Salivary gland tumours characteristically present with an enlarging mass.
      We describe an unusual presentation of a salivary gland tumour with stenosis of
      the external ear canal in the absence of a palpable mass. EMC usually arises from
      the salivary glands but isolated cases have been described arising primarily from
      the paranasal sinuses, trachea and lacrimal gland. The management of this tumour
      is still evolving with surgical excision being the main-stay of treatment. The
      efficacy of radiotherapy has not yet been established but high local recurrence
      rates despite apparently adequate excision and the possibility of a multicentric
      origin of the tumour may herald an increasing role for radiotherapy in the
      future. We stress the importance of awareness of adjacent structures when
      considering the cause of cartilaginous canal stenosis.

PMID- 8762330
TI  - Intraoral sebaceous carcinoma.
AB  - Sebaceous carcinoma arising from the buccal mucosa is very rare. Only one such
      case has been reported in the English literature. We report a second case arising
      in an 11-year-old girl.

PMID- 8762329
TI  - The detection of clinically occult nasopharyngeal carcinoma in patients following
      radiotherapy--an analysis of 69 patients.
AB  - A prospective analysis of 69 patients who had been treated for nasopharyngeal
      carcinoma (NPC) by external radiotherapy was carried out. Biopsies from the
      posterior nasopharynx were performed and analyzed by in situ hybridization using
      an antisense Epstein-Barr Early RNA (EBER) radio-labelled riboprobe. None of the
      patients had evidence of disease in the nasopharynx. One patient was found to
      have nasopharyngeal carcinoma detected only by in situ hybridization. In the
      subsequent 18-month follow-up of these clinically- and biopsy-negative patients,
      only one patient developed relapse in the nasopharynx. In situ hybridization is a
      valuable tool for the detection of NPC and should be routinely available in
      histopathology laboratories where NPC is regularly diagnosed.

PMID- 8762331
TI  - Adenoid cystic carcinoma of the maxilla--the value of histopathology in
      diagnosing a second primary.
AB  - Adenoid cystic carcinoma is the commonest tumour of minor salivary glands. In the
      case described here a pulmonary mass was found. This was likely to be a distant
      metastasis, particularly as the primary tumour was of cribriform subtype with
      perineural invasion and resection was microscopically incomplete. However,
      surgical excision of the pulmonary mass enabled histopathological studies to be
      carried out which found it to be an unrelated bronchioloalveolar carcinoma.

PMID- 8762332
TI  - Re: otological drills.

PMID- 8762333
TI  - Genetic conflicts and the paradox of sex determination: three paths to the
      evolution of female intersexuality in a mammal.
AB  - That sex determining systems ever change is paradoxical but can be explained by
      noting that conflict between selfish elements and their modifiers will often
      cause a shift in sex determining strategy. The evolution of the novel sex
      determining system of moles (Talpa europaea and T. occidentalis) may, we argue,
      be an example of just such a process. Three different models for the evolution of
      female intersexuality are presented. These all attempt to account for (1) the
      fact that a few years ago populations of moles had high frequencies of sterile XX
      individuals that were either morphologically male or intersex (other XX
      individuals were normal females) and (2) that presently, the XX individuals in
      the same population are exclusively fertile intersexes that are functionally
      female; i.e. have follicle producing ovotestes. This case history is compared to
      that of the wood lemming and two similarities are discussed. First, in both cases
      it is noted that one end product could be approached from different routes.
      Second, selfish elements may be involved in the evolution of both systems. In
      general, it is suggested that XY sex determination, far from being resilient to
      evolutionary change, is vulnerable to take-over by selfish elements. This is
      particularly the case in mammals in which transplacental interactions could allow
      manipulation of sex determination in one foetus by another. This, we also
      suggest, is a good candidate explanation for the evolution of novel sex
      determination in Talpa.

PMID- 8762334
TI  - How to recognize monofunctional units in a metabolic system.
AB  - In intracellular metabolic networks, it is often useful to discern subsystems
      (modules) of which the metabolites are only produced or consumed by reactions
      within that subsystem or by a limited number of fluxes crossing the borders of
      the subsystem. In many cases such subsystems function as units with respect to
      their effect on the remainder of the system. In this paper we show that the co
      response of two metabolic variables outside that subsystem to a perturbation of a
      subsystem reaction does not depend on which subsystem reaction is perturbed if
      three conditions are fulfilled: (1) the reactions outside the subsystem are not
      affected directly by metabolites belonging to the subsystem; (2) there are no
      conservation relations linking the subsystem to the rest; and (3) the subsystem
      is linked to the remainder of the system only via one degree of freedom in
      fluxes. We propose the name "monofunctional units" for subsystems fulfilling
      these three criteria. Identification of such units greatly simplifies metabolic
      control analysis. Only one reaction per unit needs to be perturbed to analyse
      control in the system. Difficulties, such as the inaccessibility of some
      reactions to experimental perturbation, may be circumvented by perturbing another
      reaction within the unit that leads to the same co-response coefficients. The
      analysis can also serve to identify unsuspected regulatory interactions in the
      metabolic network. The differences in the behaviour between metabolic units and
      other types of subsystems are illustrated by numerical examples.

PMID- 8762335
TI  - Complex periodic behaviour in a neural network model with activity-dependent
      neurite outgrowth.
AB  - Empirical studies have demonstrated that electrical activity of the neuron can
      directly affect neurite outgrowth. High levels of activity cause neurites to
      retract, whereas low levels allow further outgrowth. Previously we studied
      networks in which all the cells reacted in the same way on electrical activity.
      Since experiments have shown that neurons may in fact react differentially, we
      study in this paper networks in which the range of activity where outgrowth takes
      place varies among cells. We show that this can lead to complex periodic
      behaviour in electrical activity and connectivity of individual cells. The
      precise behaviour depends on the spatial distribution of the cells and the
      distribution of the outgrowth properties over the cells. Any other cellular
      property that adapts slowly to electrical activity such that neuronal activity is
      attempted to be maintained at a given level, can lead to similar results.

PMID- 8762336
TI  - Phase switching of oscillatory contraction in relation to the regulation of
      amoeboid behavior by the plasmodium of Physarum polycephalum.
AB  - The plasmodium of the true slime mould Physarum polycephalum is a large aggregate
      of protoplasm and behaves like an amoeboid cell, exhibiting rhythmic contraction
      everywhere within the organism. Phase dynamics of these oscillations were studied
      in relation to the global organization of amoeboid behavior, by analysing the
      thickness oscillation, isotonic tension and the motive force of the streaming.
      Usually the plasmodium showed synchrony, the phase of the oscillation being the
      same everywhere excepting the peripheral part. We found several situations where
      this in-phase relationship switched to anti-phase. This occurred either at the
      early stages of the plasmodial coalescence, or when a single plasmodium was
      nearly separated by partition, or when the streaming of the protoplasm was
      hindered by applying the hydrostatic pressure. Furthermore, the motive force of
      the protoplasmic streaming increased once the anti-phase relationship was
      established. In this way, the weak interactions among plasmodial parts induce the
      switching of phase relationship from in-phase to anti-phase, and this transition
      in turn acts to increase the interaction by promoting a rapid mixing of the
      protoplasm. This global feedback mechanism by phase switching should help
      maintain a large single plasmodium without separating into parts. The possible
      mechanism of phase switching is discussed in terms of coupled nonlinear
      oscillators.

PMID- 8762337
TI  - Preconceptual programming and sexual orientation: a hypothesis.
AB  - To date, biological explanations of sexual orientation have broadly focused on
      genes and/or prenatal hormonal environments which are thought to act on the brain
      to provide the neural circuitry on which sexual orientation is inscribed. The
      proposed models are open to criticism when applied to a healthy population at
      large because of the implied reference to developmental anomalies. For this
      reason the present paper challenges the traditional viewpoint and hypothesizes
      that the foundation of adult sexual orientation may be the result of adaptive
      programming beginning before conception. According to this hypothesis the
      continuum spanning human sexuality has its etiology defined in terms of male and
      female-mediated forms of selective preconceptual marking. The hypothesis also
      assumes that, via the mechanism of genomic imprinting, the imprinted gene is able
      to switch through different states of potential activity from the incomplete to
      the fully penetrant state resulting in a continuum of orientations ranging from
      asexual, through graded bisexual to homosexual. An adaptive preconceptual program
      has biological significance as it ensures a generational preparedness for the
      prevailing conditions. The physiological aspects and circumstantial evidences
      which were important in developing the new hypothesis are also described.

PMID- 8762338
TI  - Epidemiology of pelvic ring injuries.
AB  - 3260 patients with pelvic and acetabular fractures were assessed using a
      standardized documentation form by collating the data on 1905 patients treated at
      the Department of Traumatology of the Hannover Medical School together with those
      patients treated between 1991 and 1993 in the German Multicentre Study Group
      (Pelvis) of the German Trauma Society and the German Section of the AO
      International. 2551 patients had pelvic ring injuries. 61.7% of the patients were
      multiply injured. 12.2% were suffering a complex pelvic trauma defined as a
      pelvic injury with concomitant soft tissue injury. The pelvic ring fracture was
      classified as stable in 54.8% (type A injury), as rotationally unstable in 24.7%
      (type B injury), and as unstable in translation in 20.5% (type C injury). There
      were concomitant acetabular fractures in 15.7%. The most frequent single lesions
      affecting the pelvic girdle were fractures of the ischiopubic bones (transpubic
      instability), injuries involving the sacroiliac joint (transiliosacral
      instability), and sacral fractures (transsacral instability). The overall rate of
      operative stabilizations was 21.6%. Type B injuries were stabilized in 28.9% and
      type C injuries in 46.7%. The overall mortality rate was 13.4%, depending
      significantly on the associated extrapelvic trauma. In complex pelvic injuries,
      the mortality rate was 31.1% whereas for pelvic fractures without concomitant
      soft tissue injury the rate was only 10.8%.

PMID- 8762339
TI  - Volume changes within the true pelvis during disruption of the pelvic ring--where
      does the haemorrhage go?
AB  - Fractures of the pelvis are not only common but are very varied in their
      complexity. They represent 3% of all fractures (1), they account for 1 in every
      1000 surgical admissions and are the third most commonly encountered injury in
      motor vehicle accident fatalities (2). However, only a small percentage of all
      pelvic fractures are associated with major disruption of the pelvic ring (3).
      Life threatening haemorrhage is a frequent complication of major pelvic fractures
      (1, 4) and haemorrhage is the leading cause of death in these patients (5, 6). It
      was believed that fracture and subsequent displacement of the ring greatly
      increased pelvic volume. However, clinical practice seemed to indicate that this
      might not be true. This study aimed to assess the change in pelvic volume which
      occurs in severely displaced pelvic fractures. A model of the bony pelvis was
      designed to permit extreme displacements of the symphyseal and sacroiliac joints.
      The volume of a polythene balloon placed within the true pelvis was measured as
      an indication of true pelvic volume. Our finding was that the increase in the
      volume of the true pelvis which occurs in a fracture with massive diastasis is
      much smaller than previously assumed.

PMID- 8762340
TI  - The early management of pelvic and acetabular fractures.
AB  - One hundred consecutive referrals with pelvic and acetabular fractures treated
      over a three year period were reviewed with regard to their early management.
      Early management was subdivided into four areas: 1. initial assessment and
      treatment; 2. imaging; 3. referral; 4. management of associated injuries. The
      cases comprised 26 pelvic fractures (18 treated operatively), 69 acetabular
      fractures (50 treated operatively), and 5 combination fractures (3 treated
      operatively). Guidelines were laid down in each of the four areas of management
      and each patient's management was compared with this ideal. 56% of cases had
      deficient management by our criteria. There were important failures in diagnosis
      and early treatment of these complex injuries. A set of simple guidelines is
      offered to help improve the situation.

PMID- 8762341
TI  - Algorithms for early management of pelvic fractures.
AB  - The successful management of pelvic fractures depends upon proper diagnosis and
      timely treatment. Severe pelvic fractures are life-threatening injuries in which
      a clear-cut treatment strategy is required to make decisions within the shortest
      possible time. An algorithm is presented in the form of a flow chart that has
      proven useful in facing difficult situations in the initial management of pelvic
      fractures. Decision-making is based on progressive clinical examination and a
      series of key questions. The sequence starts with the arrival of the patient,
      followed by the resuscitation phase, proceding through the initial examination
      and assessment of the patient to the final diagnosis and appropriate treatment. A
      safe approach to pelvic fractures is gained by following the proposed algorithm.
      The algorithm is an excellent teaching tool, but no guarantee can be given since
      every case is different and requires a specific approach.

PMID- 8762342
TI  - The pelvic C-clamp for the emergency treatment of unstable pelvic ring injuries.
      A report on clinical experience of 30 cases.
AB  - An unstable pelvic ring injury was stabilized with the AO C-clamp in thirty
      multiply injured patients. The average ISS was 29 (19-57). Transfusions totalled
      24 units of blood/fresh frozen plasma/platelets (0-117) on average. In 12 cases,
      the application was for an unstable fracture alone, in 18 patients there was an
      unstable haemodynamic situation in addition. The application was haemodynamically
      effective in 10 cases. In 66% of cases, the initial reduction was good and the
      anatomy of the pelvic ring was adequately restored. Ten patients (33%) died; five
      during the first hours after admission due to haemorrhagic shock; the remaining
      five from multiple organ failure, fat embolism and head injury. Definitive
      stabilization was accomplished after 4.5 days on average (0-15). Complications
      relating directly to the clamp did not occur. The application of the C-clamp has
      a clear place in the management of polytraumatized patients with linear unstable
      pelvic ring injuries.

PMID- 8762343
TI  - Clinical experience with two types of pelvic C-clamps for unstable pelvic ring
      injuries.
AB  - The emergency stabilization of unstable pelvic injuries, in particular, injuries
      to the posterior pelvic ring, can be achieved following reduction by application
      of the pelvic C-clamp. This and other procedures contribute to controlling what
      is almost always a life-threatening blood loss. The pelvic C-clamp is a temporary
      measure preceding definitive treatment of the injury. If this procedure is to
      have an optimal and lasting effect, the clamp must be applied correctly, provide
      adequate compression and stability, and be easy to handle. In one year, we
      applied the AO and ACE pelvic clamps in 9 clinical cases. Satisfactory primary
      compression and stability were achieved for unstable injuries with both clamps.
      It was more difficult to achieve good rotational stability as required for
      subsequent treatment with the ACE clamp due to its construction design.

PMID- 8762344
TI  - 50 years of publishing social and preventive medicine and epidemiology and
      community health.

PMID- 8762345
TI  - A documentation centre on socioeconomic inequalities in health.

PMID- 8762346
TI  - Community health: the risks of confusion and complacency.

PMID- 8762347
TI  - Levels of mortality, education, and social conditions in the 107 local education
      authority areas of England.
AB  - STUDY OBJECTIVE: To investigate the relationships between education, social
      conditions, and mortality. DESIGN: An ecological study relating several measures
      of mortality to local rates of educational attainment at age 15/16 years and
      scores on the Department of the Environment's index of local conditions. SETTING:
      England and its 107 local education authority areas in 1991. MAIN RESULTS:
      Educational attainment was closely associated with all cause, coronary, and
      infant mortality and strongly associated with the index of local conditions. This
      social index was also closely associated with all the measures of mortality. In
      multiple regression, the social index was the stronger correlate of all cause
      mortality but for coronary and infant mortality, educational attainment remained
      highly statistically significant. CONCLUSIONS: Area levels of both educational
      attainment and deprivation-affluence are strong correlates of local mortality
      rates in England. In these analyses educational attainment may be indexing the
      general cultural level of a community. Preliminary investigation with these
      ecological data suggests that deprivation-affluence has the stronger association
      but a surer assessment of their relative importance will require individual level
      information.

PMID- 8762348
TI  - An epidemiological study after a water contamination incident near Worcester,
      England in April 1994.
AB  - STUDY OBJECTIVES: To investigate whether exposure to tap water contaminated in a
      major river pollution incident with 2 ethyl 5,5 dimethyl 1,3 dioxane (EDD) and 2
      ethyl 4 methyl 1,3 dioxolane (EMD) was associated with an increase of self
      reported symptoms. To assess the extent of association between noticing the water
      had an unusual taste or odour and self reported symptoms. DESIGN: Retrospective
      cohort study. SETTING: A city and two nearby towns in a semi-rural area of
      England, UK. PARTICIPANTS: A total of 3861 people who replied to a postal
      questionnaire asking about symptoms and water consumption sent to a sample of
      1000 households in each of three areas--one area supplied with contaminated water
      (study group) and two control areas that were unaffected (control groups). MAIN
      RESULTS: The household response rates were 65% for the study group and 56% and
      57% for the two control groups. Self reporting of 10 individual symptoms was
      significantly increased in the study group compared with controls. Within the
      study group, reporting of one or more symptoms was significantly higher in
      subjects who consumed contaminated water but not among subjects who used it to
      wash or cook. Subjects who drank contaminated water showed a dose-response
      relationship for self reporting of one or more symptoms and for seven individual
      symptoms. Within the study group, however, only 62% (867 of 1398 subjects)
      noticed that the water had an unusual taste or odour. Among subjects who did not
      notice that the water had an unusual taste or odour, no association was found
      between drinking contaminated water and reporting one or more symptoms, or
      between drinking contaminated water and reporting of individual symptoms,
      although a dose-response relationship was shown between the amount of water
      consumed and self reporting of nausea. Among subjects who noticed the water had
      an unusual taste or odour, both an association and a dose-response relationship
      were found between consumption of contaminated water and the self reporting of
      six symptoms--diarrhoea, nausea, headache, stomach pains, skin irritation, and
      itchy eyes. CONCLUSIONS: Higher rates of symptom reporting were associated with
      the water contamination incident. Reported symptoms seemed, however, to be
      associated with the ability to detect an unusual taste or odour in the water.
      Because concentrations of the contaminants would be expected to be evenly
      distributed in the tap water in the affected area, irrespective of taste or
      odour, and because of the known toxicity of the parent compounds of EMD and EDD,
      it is concluded that the increase in self reported symptoms in the study group
      respondents was associated with noticing the unpleasant taste or odour of the tap
      water and not with the chemical contamination. It is concluded that the observed
      increase in reporting of nausea with increasing water consumption was due to
      public anxiety caused by the incident but did not pose a serious risk to the
      public's health. The increase in self reported symptoms in the area affected by
      the contamination was an important reminder of the wider health implications of
      "health scares".

PMID- 8762349
TI  - Epidemiology and patterns of hospital use after parasuicide in the south west of
      England.
AB  - OBJECTIVE: To describe the epidemiology, management, and outcome of parasuicide
      in the south west of England. DESIGN: Descriptive analysis using routine
      information systems. SETTING: The former South Western Regional Health Authority,
      population aged 10 and over: 2.9 million. SUBJECTS: These comprised 5080
      residents of the South Western Health Region, admitted on 5770 occasions for
      parasuicide between April 1992 and March 1993 to hospitals in the south west.
      MAIN OUTCOME MEASURES: Person based age and sex standardised admission ratios for
      parasuicide; readmission for parasuicide in the subsequent 12 months; admission
      to psychiatric hospital after parasuicide; in-hospital mortality for those
      admitted after attempted suicide. RESULTS: The overall rate of parasuicide
      admission was 174 per 100,000 per year. Rates were highest in males aged 20-24
      (381 per 100,000) and in females aged 15-19 (625 per 100,000). Parasuicide is the
      third most frequent cause of acute medical admission in the south west. A total
      of 10.0% of admissions received psychiatric inpatient care as a direct result of
      their parasuicide admission and 10.1% were readmitted in the following 12 months
      with a repeat episode of parasuicide. Significant variations in standardised
      admission ratios for parasuicide were observed between the districts. Some of
      this variation is related to socioeconomic differences between districts, the
      rest is probably due to differences in practice between districts. There is no
      clear evidence that these variations result in differences in readmission rates.
      Districts where psychiatric inpatient facilities were located on the same site as
      the general hospital tended to admit a greater percentage of parasuicide patients
      for psychiatric inpatient care. A quarter of all suicide deaths from overdose
      occurred in hospital. It is estimated that there are 87,000 parasuicide
      admissions in England and Wales annually. CONCLUSIONS: Parasuicide is a common
      cause of acute hospital admission and there is evidence that hospital admission
      practices for parasuicide vary across the south west. Randomised controlled
      trials are needed to evaluate the most appropriate form of management for those
      patients who do not require admission on medical grounds.

PMID- 8762350
TI  - Suicide from the Clifton Suspension Bridge in England.
AB  - OBJECTIVES: To examine the epidemiology of suicide by jumping from the Clifton
      Suspension Bridge and its impact on local patterns of suicide. DESIGN: Case
      control study of falls from the bridge (1974-93) matched by age and sex with
      those using other methods of suicide. Routine OPCS mortality statistics for
      Bristol and District Health Authority. SETTING: The County of Avon and the
      Bristol and District Health Authority. SUBJECTS: 1. Individuals given coroners'
      verdicts of suicide, "open", or misadventure after falls from the suspension
      bridge and 127 matched control suicides using other methods. 2. All deaths from
      suicide within the Bristol and District Health Authority 1982-91. MAIN OUTCOME
      MEASURES: Past psychiatric history, demographic characteristics of suicides, and
      proximity of place of residence to the bridge. RESULTS: There were 127 falls from
      the Clifton Suspension Bridge between 1974 and 1993. The mean age was 35.4 years
      for males (n = 93) and 35.5 for females (n = 34). Those who committed suicide by
      jumping were no more likely to have psychiatric histories than controls (95% CI
      of difference--1.17%, 23.2%) and were no more likely to have been psychiatric
      inpatients in the past (95% CI of difference--10.2%, 13.3%). Mean distance of
      residence from the bridge differed little between jumping suicides and controls
      (difference 1.7 km 95% CI 0.5, 3.9 km). Altogether 10.2% of jumpers had a past
      history of schizophrenia. Suicide by jumping is significantly more common in the
      Bristol and District Health Authority (9.3% of all suicides; 95% CI 7.6%, 11.3%)
      than in England and Wales (4.9% of suicides). CONCLUSIONS: Patterns of suicide in
      the Bristol and District Health Authority are affected by the presence of the
      Clifton Suspension Bridge. Those who commit suicide by jumping from the bridge do
      not differ significantly from those using other methods of suicide. Provision of
      safety measures on the bridge may lead to the prevention of some suicides.

PMID- 8762351
TI  - Psychosocial resources and persistent smoking in early pregnancy--a population
      study of women in their first pregnancy in Sweden.
AB  - STUDY OBJECTIVE: To test the stress hypothesis by characterising women during
      their first pregnancy who continue to smoke in early pregnancy in comparison with
      women who quit smoking, with special reference to psychosocial factors like
      social network, social support, demands, and control in work and daily life.
      DESIGN: The study is based on a cohort of primigravidas followed during
      pregnancy. Data were collected by self administered questionnaires during the
      pregnant womens' first antenatal visit at about 12 weeks. SETTING: The study was
      performed in the antenatal clinics in the city of Malmo, Sweden. PARTICIPANTS:
      The participants were all primigravidas living in the city of Malmo, Sweden, over
      a one year period, 1991-92. A total of 872 (87.7%) of the 994 invited women
      agreed to participate. The population of this study on smoking includes all
      primigravidas who at the time of conception were smoking (n = 404, 46.3%). MAIN
      RESULTS: At the first antenatal visit (63.6% (n = 257) of the prepregnancy
      smokers were still smoking (a total smoking prevalence of 29.5%). The pregnant
      smokers were on average younger and had a lower educational level. The highest
      relative risk (RR) of continued smoking was found among unmarried women RR 2.7
      (95% confidence interval) (1.5, 4.8), women having unplanned pregnancies RR 2.2
      (1.2, 4.0) and those with a low social participation RR 1.6 (1.0, 2.7), low
      instrumental support RR 2.6 (1.2, 6.0), low support from the child's father RR
      2.1 (1.0, 4.2) and those exposed to job strain RR = 2.3 (1.1, 4.8). The
      associations were independent of potential confounders such as age, educational
      level, nationality, cohabiting status, passive smoking, and previous years of
      smoking. CONCLUSIONS: This study supports the stress hypothesis. Smoking can be
      one way women handle stress when demands become too great. In order to reduce
      smoking among pregnant women, maternity centre resources need to be focused more
      on women with low psychosocial resources who are at highest risk for continued
      smoking. It is also important to involve actively the woman's partner or other
      important people in the woman's social network.

PMID- 8762352
TI  - Features of infant exposure to tobacco smoke in a cohort study in Tasmania.
AB  - STUDY OBJECTIVES: To document changes in smoking style around infants over time
      and to identify factors associated with the smoking hygiene of mothers and
      others. DESIGN: A population based cohort study. SETTING: Population based,
      involving 22% of live births in Tasmania, Australia. PARTICIPANTS: From 1 May
      1988 to 30 April, 1993, 6109 infants and their mothers (89% of eligible infants)
      participated in the hospital and home interview of the cohort study. Infants
      eligible for cohort entry were those assessed at birth to be at a higher risk of
      SIDS. MAIN RESULTS: The overall proportion of mothers who smoked during pregnancy
      and postnatally did not decline. Increasing trends were found for mothers and
      others not smoking in the same room as baby or while holding or feeding the baby,
      significant over the five year period. Good smoking hygiene (mother not smoking
      in the same room as baby) was positively associated with--first birth (OR = 1.74
      (1.30, 2.33)), low birth weight (1.69 (1.27, 2.23)), being born after 1 May 1991
      (1.67 (1.33, 2.11)), and private health insurance status (1.39 (1.02, 1.90)).
      Good smoking hygiene was negatively associated with maternal smoking during
      pregnancy (0.50 (0.31, 0.80)), intention to bottle feed (0.62 (0.49, 0.78)), the
      level of maternal postnatal smoking, increasing numbers of smokers in the
      household, and parents cohabiting but unmarried. A similar analysis was conducted
      for other household residents who smoked. CONCLUSIONS: Changes in maternal
      smoking prevalence have been small. The exposure of infants to tobacco smoke
      postnatally has decreased significantly, although a large proportion of infants
      are still exposed to tobacco smoke. The identification of the above parental and
      infant factors associated with good smoking hygiene should be useful for health
      education planning.

PMID- 8762353
TI  - Cigarette smoking and bone mineral density in the elderly.
AB  - OBJECTIVE: To test the hypothesis that cigarette smoking is associated with
      reduced bone mineral density in elderly men and women. DESIGN: Cross sectional
      study. SUBJECTS: These comprised 224 men and 186 women aged 61-73 years, born and
      resident in East Hertfordshire. MEASUREMENTS: Lumbar spine and femoral neck bone
      mineral density (BMD) were determined by dual energy x ray absorptiometry.
      RESULTS: After adjusting for potential confounding variables, men who were
      current smokers were found to have a lumbar spine BMD that was 7.3% (95% CI 0.4,
      14.2) lower than men who had never smoked. Similarly, women who were current
      smokers had a BMD value that was 7.7% (95% CI 0.3, 15.6) lower than in women who
      had never smoked. The difference at the femoral neck was smaller and not
      statistically significant. For both men and women, each decade of smoking was
      associated with a reduction of 0.015 g/cm2 in BMD at the lumbar spine (95% CI:
      men 0.002, 0.027; women 0.003, 0.028). At the femoral neck the reduction in BMD
      was 0.011 g/cm2 (95% CI 0.003, 0.020) for men and 0.004 g/cm2 (95% CI -0.003,
      0.012) for women with each decade of smoking. CONCLUSIONS: The results show an
      adverse effect of smoking on BMD which was most noticeable at the lumbar spine,
      and seemed stronger in men than women. This effect could not be explained by
      differences in life style between smokers and nonsmokers.

PMID- 8762354
TI  - Cancer risk and prognosis in Norway: comparing women in their first marriage with
      women who have never married.
AB  - STUDY OBJECTIVE: The difference in risk of cancer between never married women and
      married women in their first marriage and whether survival from cancer was any
      different between the two groups were studied. DESIGN: This was a population
      based, nested case-control study of cancer in Norwegian women diagnosed between
      1966 and 1990, and followed up with regard to overall survival until the end of
      1991. SETTING: Norway. PARTICIPANTS: These were Norwegian women born between 1935
      and 1954. The case-control study included 12,237 married and 1466 unmarried
      cases, and 26,075 married and 2768 unmarried controls. In the survival analysis,
      11,943 married and 1473 unmarried cases were included. MAIN RESULTS: Unmarried
      women had an overall increased cancer risk (OR = 1.13, 95% CI 1.05, 1.21), which
      could be attributed to cancer of the ovaries, uterus, brain and haematological
      malignancies. For cervical and thyroid cancer, the risk was lower than for
      married women. In the survival analysis, unmarried cases had an overall 26%
      increased risk of dying (HR = 1.26, 95% CI 1.15, 1.39), after adjustment for age
      and stage at diagnosis. The increased death rate was seen for cancer of the
      cervix, lung, and thyroid. CONCLUSIONS: Since most unmarried women were
      nulliparous, this might explain their increased risk of ovarian and uterine
      cancer. The increased risk of brain tumours and haematological malignancies may
      result from selection bias, since disease among unmarried women may cause a large
      proportion to remain unmarried. The lower survival in unmarried cases may support
      the hypothesis that psychosocial factors play a role in the prognosis of cancer
      patients.

PMID- 8762355
TI  - Housing conditions and mental health in a disadvantaged area in Scotland.
AB  - OBJECTIVE: To examine the mental health impact of different aspects of poor
      housing. DESIGN: This was a post hoc analysis of data from a household interview
      survey. SETTING: A public sector housing estate on the outskirts of Glasgow.
      SUBJECTS: These comprised 114 men and 333 women aged between 17 and 65 from 451
      households. MEASURES: Dependent variable: scoring > or = 5 on the 30 item general
      health questionnaire (GHQ30). INDEPENDENT VARIABLES: self reported data on
      household composition, whether ill health was a factor in the move to the current
      dwelling, length of time at address, household income, whether the respondent was
      employed, chronic illness, and 6 problems with the dwelling. RESULTS: Reporting a
      problem with dampness was significantly and independently associated with scores
      of > or = 5 on the GHQ30 after controlling for possible confounding variables.
      CONCLUSION: Initiatives to tackle housing dampness may be important in developing
      a strategy to improve mental health for the study area. More research on the
      mental health impact of different aspects of poor housing is required.

PMID- 8762356
TI  - Epidemiological survey of rheumatic heart disease among school children in the
      Shimla Hills of northern India: prevalence and risk factors.
AB  - STUDY OBJECTIVE: To determine the prevalence of rheumatic heart disease (RHD) and
      study the relationship of this disease to factors such as age, sex, housing, and
      socioeconomic status in Shimla town and the adjoining rural area. DESIGN: A cross
      sectional survey, carried out by a specially trained examiner in cardiology.
      SETTING: The study involved high risk school children (5-16 years of age) from
      Shimla town and the adjoining rural area of Kasumpti-Suni Block in the period
      1992-93. SUBJECTS: A total of 15,080 children on the school register (8120 boys
      and 6960 girls) were examined generally and specifically for evidence of RHD.
      MAIN RESULTS: Of the 15,080 children screened, the prevalence of rheumatic fever
      (RF)/RHD was 2.98 per thousand with no significant difference between the age
      groups of 5-10 and 11-16 years or in either sex (p > 0.05). The prevalence was
      significantly greater in rural schools (4.8/1000) than in urban schools
      (1.98/1000) (p < 0.05). There was overcrowding and poor housing in most cases.
      There were fewer cases of RHD with severe valvular lesions in the younger age
      group than in the older children. The mitral valve was the valve most commonly
      affected by RF/RHD. CONCLUSIONS: RHD continues to be a serious health problem.
      Regular surveys are needed to identify cases early and to ensure secondary
      prophylaxis with penicillin is given thereby preventing recurrence of RF and
      progression of the severity of the valvular lesion. Echocardiography is necessary
      to identify cases of RF/RHD. Strategies for preventing RHD should involve primary
      prevention to avert the first attack of carditis and strengthening of secondary
      prophylaxis through improved education and motivation of patients, parents, and
      physicians.

PMID- 8762357
TI  - Age specific sensitivity and sojourn time in a breast cancer screening programme
      (DOM) in The Netherlands: a comparison of different methods.
AB  - STUDY OBJECTIVE: To estimate age dependent sensitivity and sojourn time in a
      breast cancer screening programme by different methods. POPULATION AND METHODS:
      The study population comprised women participating in the DOM project--the
      Utrecht screening programme for the early detection of breast cancer. Breast
      cancer screening prevalence data and incidence rates after a negative screen were
      used to estimate age specific sensitivity and mean sojourn time by different
      methods. MAIN RESULTS: Maximum likelihood estimates of the mean sojourn time
      varied from one year for women aged 40-49 years to three years for women over the
      age of 54. Sensitivity was calculated by two different methods. Both pointed to a
      high sensitivity (around 100%) in the age groups 40-49 and over 55 years. For
      women aged 50-54, the sensitivity varied from 63% to 100%, depending on the
      method used and the value of the baseline incidence rate. CONCLUSIONS: Different
      methods of estimating sensitivity pointed at an acceptable level in women over
      and under 50 years of age. Sojourn time, and thus the tumour growth rate, seemed
      to be age dependent. This could mean that the until now disappointing screening
      results in women under 50 years of age are not so much a result of low
      sensitivity as of a relatively high tumour growth rate in younger women.

PMID- 8762359
TI  - Response of women aged 65-74 to invitation for screening for breast cancer by
      mammography: a pilot study in London, UK.
AB  - OBJECTIVE: To investigate the response and benefits to be gained from
      mammographic screening for breast cancer in women aged 65-74, who are not
      normally invited for screening. DESIGN: This was a pilot study comprising women
      aged 65-74 who are not currently invited for routine screening under the NHS
      breast screening programme. The results from this study were compared with the
      results of routinely screened women (aged 50-64) from the same health district.
      SETTING: A mobile breast screening unit in the grounds of the Royal Free
      Hospital. SUBJECTS: These comprised 5004 women aged 65-74 registered with GPs in
      the district of Hampstead and on the family health services authority (FHSA)
      lists. A total of 168 (3.4%) were initially excluded by the general practitioner
      or FHSA, and 286 (5.9%) of the invitation letters were returned by the Post
      Office or by other people as not deliverable for some reason. MAIN OUTCOME
      MEASURES: Response rates to the invitation were assessed using three indices:
      crude population coverage rate, crude invited population coverage rate, and
      corrected invited population coverage rate. RESULTS: With regard to response
      rates, 1684 women aged 65-74 (37% of all those invited, excluding those who were
      not available) were screened, compared with 2894 (42%) women aged 50-64. The
      three response rates were higher for younger women than older: the crude
      population coverage rate was 37.1%, the crude invited population coverage rate
      was 38.9%, and the corrected invited population coverage rate was 42.1% for women
      aged 50-64, compared with 32.9%, 34.4%, and 36.8% respectively for women aged 65
      69 and 34.3%, 35.2%, and 37.2% for women aged 70-74. The rate of assessment
      increased significantly with increasing age, with 3.18% of the 50-64 population
      screened being assessed, as compared with 4.14% and 4.83% of the women aged 65-69
      and 70-74, respectively. Most biopsies done in the older women gave positive
      results, as did the biopsies from the 50-64 age group. However, the biopsy rate
      increased significantly with increasing age. The cancer detection rates in the
      women aged 65-69 and 70-74 were 14.2/1000 and 13.2/1000 compared with an incident
      screening round rate of 4.5/1000 in women aged 50-64. CONCLUSIONS: These results
      show that there is potential for similar attendance at routine screening by older
      women if they are invited in the same way as younger women. As the assessment,
      biopsy, and cancer detection rates in the older women are significantly higher
      than in the 50-64 year olds, the costs and benefits of including them in the NHS
      screening programme should be reassessed.

PMID- 8762358
TI  - Breast screening: a randomised controlled trial in UK general practice of three
      interventions designed to increase uptake.
AB  - STUDY OBJECTIVES: To determine the relative effectiveness of three interventions
      designed to increase the uptake of breast screening. DESIGN: Randomised
      controlled trial of a nurse visit with health education (group A), nurse visit
      without health education (group B), and GP letter (group C). SETTING: The area of
      south east London served by the Butterfly Walk Breast Screening Unit in
      Camberwell. PARTICIPANTS: Women aged between 50 and 64 years who were registered
      with 27 GPs in the Lambeth, Southwark and Lewisham family health services
      authority and who had not attended for first round screening. MAIN RESULTS:
      Altogether 799 women were randomly allocated to the three groups. In general,
      delivering the nurse based interventions proved difficult. In group A, 11.4% (95%
      CI 7.9, 14.9%) of women subsequently attended for screening compared with 7.8%
      (95% CI 5.1, 11.4%) in group B and 13.1% (95% CI 7.9, 18.4%) in group C. The
      differences between the groups (95% CIs) were not statistically significant: A
      versus C, -1.7% (-8.0, +4.6%); B versus C, -5.3% (-11.3, +0.7%); A versus B,
      +3.6% (-1.0, +8.2%). CONCLUSIONS: A personal letter from the GP seems to be at
      least as effective at increasing the uptake of breast screening in non-attenders
      as a nurse making a home visit to discuss the issue of breast screening, and is
      not noticeably less effective than a visit at which a health education
      intervention is delivered. It is possible that the GP letter is considerably more
      effective than either of the two interview-based interventions. With regard to
      implementing strategies which will increase breast screening uptake and are cost
      effective, further trials of similar minimal interventions in primary care are
      required.

PMID- 8762360
TI  - Health and social costs of tobacco use in Ontario, Canada, 1979 and 1988.
AB  - STUDY OBJECTIVE: This study aimed to estimate the health and social costs of
      tobacco use in Ontario, Canada. DESIGN: This was a cost-benefit analysis based on
      cross sectional data in 1988, stratified by age and sex, using an attributable
      risk model. The total cost of the consequences of tobacco use in the society
      included those costs attributed to extra deaths, disability, hospitalisation,
      physician visits, and fire losses, from tobacco use. PARTICIPANTS: The general
      population of Ontario, Canada. MAIN RESULTS: The total cost of tobacco use in
      Ontario, Canada in 1988 was estimated to be $3.623 billion--$721 million more
      than the total customer expenditure on tobacco products. Tobacco use was also
      found to be responsible for 14% of all adult deaths, 5% of all adult disability
      days, 14% of all days of hospitalisation, and 3% of all physician visits.
      Compared with previous results for Ontario (1979) the cost of the consequences of
      tobacco use had increased by about 25% and consumer expenditure by about 35% over
      the period, while the excess of consequences over expenditure fell slightly by
      about 3%. CONCLUSIONS: The annual excess of the social costs of tobacco use over
      total consumer expenditure is staggering. It is suggested that similar cost
      benefit analysis of smoking be carried out at regular intervals to monitor
      smoking trends in the society, to estimate health and social costs, and to
      provide information for the setting of targets for tobacco control and healthy
      public policies.

PMID- 8762361
TI  - Comparing survey data on functional disability: the impact of some methodological
      differences.
AB  - STUDY OBJECTIVE: To examine the impact of some differences in survey methodology
      on the prevalence of functional disability in population based surveys of the
      elderly. DESIGN AND METHODS: Nine surveys of Dutch people aged 55 years and older
      were compared to investigate the differences in the methods of data collection
      (proxy questioning, yes/no; interview versus self administered questionnaire) and
      construction of the questionnaire (wording of introductory text, activities, and
      response categories). The effect of these differences on prevalences in three
      domains of functional disability--activities of daily living, mobility, and
      communication--were studied. Both univariate analyses and multivariate logistic
      regression were used to quantify the methodological influences. RESULTS: No
      effect of proxy questioning could be shown. Self administered questionnaires
      yielded higher prevalences of disability than interviewer administered
      questionnaire--in particular for mobility (odds ratio (OR) 1.4, 95% confidence
      interval (95% CI) 1.3, 1.6) and communication (OR = 1.7, 95% CI 1.5, 1.9),
      resulting in prevalence differences of 9 and 11 percentage points respectively.
      Seemingly minor differences in the structure and wording of the questionnaires
      resulted in major differences (up to 15.6 percentage points) in prevalence
      estimates of functional disability. These differences were associated with the
      severity level of the disability indicated by the wording of the questions.
      CONCLUSIONS: Differences in survey methodology have a substantial effect on the
      prevalence estimates of disability in the elderly. These differences should be
      taken into account when making international comparisons and studying time trends
      based on survey data.

PMID- 8762362
TI  - Is the short form 36 (SF-36) suitable for routine health outcomes assessment in
      health care for older people? Evidence from preliminary work in community based
      health services in England.
AB  - STUDY OBJECTIVE: To examine the short form 36 (SF-36) health status measure when
      used to assess older people's views of the outcome of community based health
      care. DESIGN: Completion of a structured questionnaire, before and after
      intervention alongside in-depth interviews with a subsample of the interviewees.
      SETTING: Community based continence and mental health services in two health
      authorities in the North West Health Region. PATIENTS: Forty seven older people
      newly referred to mental health services or continence services between December
      1992 and April 1993 participated. MAIN RESULTS: The SF-36 showed minimal change
      over time for both patient groups. The more detailed in-depth interviews showed
      that people experienced positive changes and derived value from contact with
      services in a number of important ways. For many reasons these benefits were not
      reflected in their SF-36 scores. CONCLUSIONS: The SF-36 is not likely to be the
      "measure of choice" for this type of evaluation, particularly where it involves
      older patient groups who have high levels of comorbidity. The content of the SF
      36 and its lack of detail for individual assessment of change means it masks
      rather than illuminates patients' views of outcome.

PMID- 8762363
TI  - Estimating the point accuracy of population registers using capture-recapture
      methods in Scotland.
AB  - STUDY OBJECTIVE: To estimate the point accuracy of adult registration on the
      community health index (CHI) by comparing it with the electoral register (ER) and
      the community charge register (CCR). DESIGN: Survey of overlapping samples from
      three registers to ascertain whether respondents were living at the addresses
      given on the registers, analysed by capture-recapture methods. SETTING: Aberdeen
      North and South parliamentary constituencies. PARTICIPANTS: Random samples of
      adult registrants aged at least 18 years from the CHI (n = 1000), ER (n = 998),
      and CCR (n = 956). MAIN RESULTS: Estimated sensitivities (the proportions of the
      target population registered at the address where they live) were: CHI--84.6%
      (95% confidence limits 82.4%, 86.7%); ER--90.0% (87.5%, 92.5%), and CCR--87.7%
      (85.3%, 90.3%). Positive predictive values (the proportions of registrants who
      were living at their stated addresses) were: CHI--84.6% (82.2%, 87.0%); ER--94.0%
      (90.9%, 97.1%), and CCR--93.7% (91.7%, 95.7%). CONCLUSIONS: The CHI assessed in
      this study was significantly less sensitive and predictive than the corresponding
      ER and CCR. Capture-recapture methods are effective in assessing the accuracy of
      population registers.

PMID- 8762364
TI  - Geographical distribution of risk factors and incidence of invasive cervical
      cancer in south east China.

PMID- 8762365
TI  - Desire for the body normal: body image and discrepancies between self reported
      and measured height and weight in a British population.

PMID- 8762366
TI  - The relationship between outdoor temperature and the frequency of falls among the
      elderly in Finland.

PMID- 8762367
TI  - Public health medicine and primary care.

PMID- 8762368
TI  - Getting to GRIP with a problem.

PMID- 8762369
TI  - Emotional reactions and colposcopy.

PMID- 8762370
TI  - Review of the article by Knox: leukemia clusters in childhood.

PMID- 8762371
TI  - Smoking and health promotion in Nazi Germany.

PMID- 8762372
TI  - Cohort analysis of mortality rates as an historical or narrative technique.
AB  - A history of cohort analysis has been given, and it has been pointed out that the
      bulk of the literature on the subject has dealt with concepts that assume either
      that graduation and possibly extrapolation are desirable, preferably in
      conformity with some formula expressing what is implicitly accepted as a "law of
      mortality", or that, whether or not a fixed pattern of mortality exists, the
      intensity of mortality risk is largely determined in early life. The view is
      advanced that either concept alone, is, or both concepts together are, inadequate
      and may lead to an improper assessment of the nature-nurture complex, since
      environment and therapeutic measures are constantly changing. The plea is made
      for the technique of cohort analysis to be used as a narrative or historical
      technique, and for a synthesis of knowledge derived from social history, medical
      history, and cohort analysis to be made to interpret the narrative. The effects
      of a changing rate on the mortality pattern as depicted by date-contour analysis
      and cohort analysis are outlined and the danger of basing biological theories on
      the mortality pattern revealed by date-contour analysis alone is indicated. This
      point is illustrated by reference to a recent theory that has been based on such
      an analysis.

PMID- 8762373
TI  - An appreciation of "Cohort analysis of mortality rates as an historical or
      narrative technique" (RAM Case)

PMID- 8762374
TI  - Research on injury prevention: time for an international agenda?
AB  - OBJECTIVE: To propose an initial agenda for a systematic international research
      strategy designed to meet the information needs of injury prevention worldwide.
      CRITERIA FOR INCLUSION AND EXCLUSION OF ARTICLES: The world literature since 1977
      was surveyed to obtain an overview of the current research effort on injury
      epidemiology and prevention. Articles were cited to illustrate the breadth and
      nature of work published on the topic with special reference to the prevention of
      home and traffic injuries. CONCLUSIONS: There has been a recent upsurge of
      interest in injury prevention, although much of the work has been descriptive
      rather than analytical or evaluative. The implementation of existing knowledge
      has been patchy. To meet the information needs of effective injury prevention,
      several elements of an international research agenda are proposed. These include:
      the achievement of a consensus on terminology, definition, and classification;
      clarification of the roles of social deprivation, gender, risk taking behaviour,
      personality, stress, alcohol, drugs, chronic illness, and disability in the
      aetiology of injury; the development of multi-agency models of good injury
      prevention practice; the evaluation of counter-measures; the development and
      evaluation of routine injury surveillance systems.

PMID- 8762376
TI  - Ethnic differences in mortality from cardiovascular disease in the UK: do they
      persist in people with diabetes?
AB  - STUDY OBJECTIVE: To determine whether ethnic differences in cardiovascular
      disease mortality persist in people with non-insulin-dependent diabetes mellitus.
      DESIGN: This was an ecological study in which routine mortality data from 1985
      86, which coded all mentioned causes of death, provided the numerator. The UK
      population derived from 1981 census formed the denominator. SETTING: United
      Kingdom. PARTICIPANTS: Records of all deaths in people aged 45 years and above
      were extracted if diabetes was mentioned anywhere on the death certificate. The
      denominator was aged five years to approximate to the 1986 population. Mortality
      rates where a cardiovascular underlying cause was given were compared between
      South Asians, African-Caribbeans, and those born in England and Wales. The latter
      group formed the standard for directly standardised rate ratios. MAIN RESULTS:
      Mortality from heart disease was approximately three times higher in diabetic
      South Asian born men and women than in those with diabetes born in England and
      Wales. This ethnic difference was greatest in the younger age group. Conversely,
      stroke mortality rates in African-Caribbeans were 3.5-4 times higher than those
      in the England and Wales population. Despite this high mortality from stroke,
      ischaemic heart disease death rates were not high in African-Caribbean men.
      CONCLUSIONS: Ethnic differences in cardiovascular mortality persisted and were
      greater in those with diabetes. Thus the high risk of heart disease should be
      targeted for intervention in South Asians, and the high rates of stroke targeted
      in African-Caribbeans.

PMID- 8762375
TI  - Effect of diet and physical exercise intervention programmes on coronary heart
      disease risk in smoking and non-smoking men in Sweden.
AB  - STUDY OBJECTIVE: To investigate differences between smokers and non-smokers in
      health behaviour, cardiovascular risk factors, coronary heart disease (CHD)
      risks, health knowledge, health attitudes, and compliance with a CHD prevention
      programme. DESIGN: Differences between smokers and non-smokers were studied via
      medical examinations, questionnaires, physical exercise activity logs, and food
      record sheets. Data were analysed using univariate and multivariate analyses. The
      five and 10 year CHD risks were assessed using the Framingham CHD risk estimate.
      SETTING: The Karolinska Hospital, Stockholm, and Sollentuna Primary Health
      Centre, Sollentuna, Sweden. PARTICIPANTS: The analyses were based on 158 healthy
      smoking and non-smoking men aged 35-60 years with raised cardiovascular risk
      factors who enrolled in controlled, randomised six month diet and exercise
      programmes. MAIN RESULTS: Discriminant analysis suggested that smokers, compared
      with non-smokers, were characterised by a higher alcohol energy percent, lower
      HDL cholesterol concentration, lower systolic blood pressure, and a higher
      plasminogen activator inhibitor-1 (PAI-1) value. Knowledge of the risk factors
      for CHD was not a discriminating factor. Both smokers and non-smokers increased
      the exercise taken, improved their diet, and lowered their CHD risk. Before, as
      well as after the intervention, smokers had a higher CHD risk than non-smokers.
      CONCLUSIONS: The best CHD prevention action that could be taken by smokers would
      of course be to quit smoking. Those who cannot stop should be encouraged to
      improve their diet and increase the amount of physical exercise they take in
      order to reduce the health hazards of their smoking behaviour.

PMID- 8762377
TI  - Prevalence of self reported stroke in a population in northern England.
AB  - STUDY OBJECTIVE: The aim of this study was to determine the prevalence of stroke
      survivors in a health district population aged 55 years and over. DESIGN: This
      was a point prevalence study using two-stage postal questionnaires sent to an age
      stratified random sample of the population. SETTING: A district health authority
      in northern England with a resident population of 723,000. SUBJECTS: Altogether
      18,827 residents aged 55 years or over. MAIN RESULTS: Prevalence was found to
      increase with age and, apart from the very elderly, males had a higher prevalence
      than females. Overall prevalence was found to be 46.8/1,000 (95% CI 42.5, 51.6).
      23% of respondents reported full recovery from stroke. Cognitive impairments
      (33%), problems with lower limbs (33% for right leg; 27% for left leg) and speech
      difficulties (27%) were the most common residual impairments. CONCLUSIONS:
      Current guidelines to purchasers on the provision of services to those who have
      had a stroke may under-estimate prevalence rates by as much as 50%. This could
      lead to a shortfall in provision of services designed to support people in the
      months and years following their stroke.

PMID- 8762378
TI  - Risk factor analysis of data from assessment clinics in the UK breast screening
      programme: a case-control study in Portsmouth and Southampton.
AB  - STUDY OBJECTIVES: The aim was to quantify the influence of demographic and
      reproductive factors on breast cancer. The subjects' path through the screening
      clinic, the inherent differences between the control groups, and the possible
      biases when using screening programmes were also considered. DESIGN: A case
      control study using both personal contact and postal questionnaires to gather
      demographic and reproductive information. SETTING: Women attending two breast
      screening recall clinics in Portsmouth and Southampton over the period 1990-92.
      PARTICIPANTS: Altogether 1813 subjects between the ages of 50 and 65 years. The
      subjects' disease status was ascertained using a mammography and classified into
      four categories: 253 breast cancer (cases); 207 benign breast disease (BD); 410
      requiring early rescreen (ER); and 943 for standard recall (SR). The BD, ER, and
      SR groups were used as separate controls. MAIN RESULTS: Of the factors considered
      here, the only two that showed a consistently significant effect on the risk of
      breast cancer were age and body mass index (BMI). Odds ratios were calculated for
      five yearly age groups and four groups of BMI using the youngest and lightest
      group as the baseline, respectively. There seemed to be an increase in the risk
      of breast cancer for increasing age for each comparison made (for cases v SR:OR
      (95% CI) = 1.60 (1.10, 2.34), 2.54 (1.76, 3.68)). All subjects above the lowest
      quartile of BMI experienced increased risk, although a trend was not clear (for
      cases v SR: OR (95% CI) = 1.66 (1.03, 2.66), 1.37 (0.86, 2.20), 1.98 (1.24,
      3.15)). CONCLUSIONS: Various other potential risk factors were found to be
      inconsistently significant depending on choice of control group. This may help in
      understanding the differences between the three control groups used.

PMID- 8762379
TI  - The effects of illness on quality of life: findings from a survey of households
      in Great Britain.
AB  - STUDY OBJECTIVE: To obtain national population norms on pertinent domains of
      quality of life, and the relative importance of these domains to people with
      reported longstanding illness. DESIGN AND SETTING: The vehicle for the study was
      the Office of Population Censuses and Surveys omnibus survey in Great Britain.
      The sampling frame was the British postcode address file of "small users",
      stratified by region and socioeconomic factors. This file includes all private
      household addresses. The postal sectors are selected with probability
      proportional to size. Within each sector 30 addresses are selected randomly with
      an target size of 2000 adults. PARTICIPANTS: The total number of adults
      interviewed was 2033 (one per sampled household), resulting in 2031 usable
      questionnaires, and representing a response rate of 77%. MAIN RESULTS: Of those
      who reported a longstanding illness, the most common, freely mentioned, first
      most important effects of the longstanding illness on their lives were (in order
      of frequency) ability to get out and about/stand/walk/go out shopping, being able
      to work/find a job, and effects on social life/leisure activities. Analysis of
      the areas of life affected by longstanding illness, showed considerable variation
      in relation to the condition. For example, respondents with mental health
      disorders (mainly depression) were most likely to report as the first most
      important effect the availability of work/ability to work, followed by social
      life/leisure activities; respondents with digestive and endocrine (for example,
      diabetes) disorders were most likely to report dietary restrictions; while
      respondents with cardiovascular disease, respiratory, and musculoskeletal
      disorders were most likely to report ability to get out and about/stand/walk/go
      out shopping. CONCLUSIONS: These results support the current trend of developing
      disease specific health related quality of life questionnaires rather than using
      generic scales.

PMID- 8762380
TI  - The prediction of different experiences of longterm illness: a longitudinal
      approach in Sweden.
AB  - STUDY OBJECTIVE: To analyse the role played by socioeconomic factors and self
      rated general health in the prediction of the reporting of severe longterm
      illness, and the extent to which these factors explain social class differences
      in the reporting of such illness. DESIGN: Analysis of panel data from the survey
      of living conditions, conducted by Statistics Sweden over the years 1979-81 and
      1986-89. SETTING: A random sample of the Swedish population, interviewed in 1979
      81 and then re-interviewed in 1986-89. PARTICIPANTS: A representative sample of
      3889 employed Swedish people, aged 16-65 years. MAIN RESULTS: Socioeconomic and
      individual factors predict severe longterm illness regardless of the kind of
      reported disorder from which the subject suffers. The main predictive factor
      involved is health self rated as fair/poor, but exposure to high physical job
      demands proved to be the main explanation of the role played by socioeconomic
      class. There was a significant interaction effect between self rated general
      health and physical job demands with regard to the experience of severe illness.
      CONCLUSIONS: The results of the study strengthen the hypothesis that manual
      workers are not only more exposed to causes of illness that have important
      individual and social consequences, but also to the personal factors that
      determine different experiences of illness. Interaction between these two kinds
      of factors (job demands and self rated health) suggests that socioeconomic and
      individual factors play different but complementary roles in the causal process
      leading to the experience of severe longterm illness.

PMID- 8762381
TI  - Child pedestrian injury rates: the importance of "exposure to risk" relating to
      socioeconomic and ethnic differences, in Auckland, New Zealand.
AB  - STUDY OBJECTIVE: To examine how child pedestrian exposure to risk, as measured by
      the mean number of streets crossed, varies according to indices of material
      disadvantage and ethnic group. DESIGN: A questionnaire on pedestrian exposure to
      risk was distributed to children for completion by parents and return to school.
      Children from 40 schools were selected using a probability cluster design.
      SETTING: The Auckland region of New Zealand. SUBJECTS: Questionnaires were
      distributed to 3388 pupils of whom 2873 (85%) completed and returned the
      questionnaire. RESULTS: The mean number of streets crossed was 2.19 (95%
      confidence interval 1.82, 2.56) at age 6 years and 2.80 (2.42, 3.17) at age 9
      years. The mean number of streets crossed for boys (2.57 (2.15, 2.98)) was
      similar to that for girls (2.38 (2.05, 2.72)). The mean number of streets crossed
      by Pacific Island children was 4.87 (4.01, 5.73), more than twice the number
      crossed by children of predominantly European origin (1.90 (1.65, 2.15)).
      Children from families without a car crossed an average of 5.34 (4.35, 6.34)
      streets, compared with 2.90 (2.50, 3.31) streets for children from families with
      one car, and 1.97 (1.65, 2.29) streets for children from families with two or
      more cars. CONCLUSION: There are large differences in pedistrian exposure to risk
      in relation to ethnic group and levels of car ownership. These differences may
      explain ethnic and socioeconomic differentials in child pedestrian injury rates.

PMID- 8762382
TI  - Musculoskeletal pain and smoking in Norway.
AB  - OBJECTIVE: To examine the association between musculoskeletal pain and smoking.
      DESIGN: Cross sectional, national interview survey. SETTING: All individuals in a
      representative sample of households in Norway in 1985. SUBJECTS: A total of 6681
      persons aged 16 to 66 years old. people in institutions were not included.
      OUTCOME MEASURES: Gender specific and age specific prevalence rates for pain in
      the cervical region/upper limbs, back, and lower limbs. RESULTS: Current smoking
      was independently associated with musculoskeletal pain (odds ratio (OR) 1.69; 95%
      confidence interval (95% CI) 1.45, 1.97) after adjustment for gender, age,
      comorbidity, mental distress, lifestyle factors, and occupation related factors.
      The association was of similar strength regarding cervical/upper limb pain (OR
      1.87; CI 1.56, 2.25) and back pain (OR 1.84; CI 1.50, 2.25) but weaker in respect
      of lower limb pain (OR 1.37; CI 1.10, 1.71). Musculoskeletal pain was often
      present in more than one site. CONCLUSION: Smoking was significantly associated
      with musculoskeletal pain after adjustment for other relevant factors.

PMID- 8762383
TI  - Importance of participation rate in sampling of data in population based studies,
      with special reference to bone mass in Sweden.
AB  - OBJECTIVE: To study the effects of participation rate in sampling on "normative"
      bone mass data. DESIGN: This was a comparison between two randomly selected
      samples from the same population. The participation rates in the two samples were
      61.9% and 83.6%. Measurements were made of bone mass at different skeletal sites
      and of muscle strength, as well as an assessment of physical activity. SETTING:
      Malmo, Sweden. SUBJECTS: There were 230 subjects (117 men, 113 women), aged 21 to
      42 years. RESULTS: Many subjects participated in both studies (163). Those who
      took part only in the study with the higher participation rate (67) almost
      invariably had higher values for bone mass density at the sites measured (up to
      7.6% for men) than participants in the study with the lower participation rate.
      No differences in muscle strength were recorded. CONCLUSION: A high degree of
      compliance is important to achieve a reliable result in determining normal values
      in population based studies.

PMID- 8762384
TI  - Risk factors for hepatitis C virus infection among blood donors in an HIV
      epidemic area in Thailand.
AB  - OBJECTIVE: The role of sexual transmission in hepatitis C virus (HCV) infection
      has not yet been completely elucidated. This study aimed to compare the risk
      factors for HCV and human immunodeficiency virus (HIV) infection in an HIV
      epidemic area of Thailand where HIV is mainly transmitted heterosexually. DESIGN
      AND SUBJECTS: Sera from 3053 blood donors were collected and tested for HCV and
      HIV between January and March 1994. Altogether 1756 (57.5%) of the donors were
      interviewed about demographics and several risk factors. RESULTS: The prevalence
      rates of HIV and HCV infections determined by antibody assays were 2.3% and 2.2%,
      respectively. Sexual risk factors were clearly shown among anti-HIV positive
      donors. These clear associations were not found, however, among anti-HCV positive
      donors. In contrast, previous histories of injecting drug use and being tattooed
      were found in some anti-HCV positive donors but less frequently in anti-HIV
      positive donors. CONCLUSIONS: Sexual transmission may play a relatively minor
      role in HCV transmission compared with HIV, in this area.

PMID- 8762385
TI  - Hand searching the Journal of Epidemiology and Community Health as part of th
      Cochrane Collaboration.
AB  - STUDY OBJECTIVE: To identify randomised controlled trials (RCTs) published in the
      Journal of Epidemiology and Community Health and to explore the contribution of
      these to the evaluation of public health issues. DESIGN: Hand searching of the
      journal by both authors with independent assessment of topics of the reports and
      of their relevance to the Cochrane Collaboration. Agreement was assessed using
      kappa scores. SETTING: All papers and letters published in the journal from the
      first issue to the end of 1994. SUBJECTS: Reports that might be RCTs were
      collected and classified into seven categories: definitely/probably/possibly RCTs
      or quasi-RCTs; or none of these. MAIN RESULTS: Eighty two definite RCTs were
      identified and a further 23 were probably/possibly RCTs or quasi-RCTs. Most
      reports dealt with health education, drug treatments, or "other" health service
      interventions. Both authors failed to identify a number of trials on hand
      searching. CONCLUSIONS: The journal has published many trials of importance to
      the development of evidence-based public health policy. Hand searching may need
      to be done independently by more than one person.

PMID- 8762386
TI  - Prioritising elective care: a cost utility analysis of orthopaedics in the north
      west of England.
AB  - STUDY OBJECTIVE: To produce a priority list for purchasers to use when purchasing
      elective care in the speciality of orthopaedics so that efficiency in health care
      purchasing (that is, maximising the benefit per unit of resource available for
      the resident population) can be achieved. DESIGN: The study used cost utility
      analysis in the elective speciality of orthopaedics. The diagnostic groups in the
      study were chosen on the basis of those conditions that constituted the greatest
      proportion of the orthopaedic waiting list, and consequently the greatest
      proportion of activity within the speciality. Costs were derived by two methods:
      the extra contractual referral tariff (ECR) and individual patient based
      costings. Outcome was assessed before surgery and again approximately six months
      afterwards. The outcome of the procedures was derived in two ways: Rosser and
      EuroQol indices. SETTING: The study took place at Wrightington hospital, a
      specialist orthopaedic hospital in north west England. PATIENTS: Prospective
      assessments were obtained from 99 patients for nine orthopaedics procedures. All
      the patients were individually interviewed on each occasion. Rosser and EuroQol
      assessments were completed for each patient by the patient and the patient's
      consultant before and after surgery. MAIN RESULTS: Priority lists presenting cost
      utility rankings for each of the procedures were derived from the patients' and
      consultants' assessments. CONCLUSIONS: It is feasible to generate priority lists
      in a systematic way. Purchasers may then use the results from these priority
      lists to help them maximise the benefits per unit of resource for their resident
      population.

PMID- 8762388
TI  - Using length of stay and inactive days in the hospital to assess appropriateness
      of utilisation in Barcelona, Spain.
AB  - STUDY OBJECTIVE: To compare the level of inappropriate utilisation of a teaching
      hospital in two different calendar years and to analyse the relationship between
      changes in appropriateness of utilisation and changes in average length of stay.
      DESIGN: Retrospective evaluation of the medical records of patients admitted to a
      hospital in two periods: 1988 and 1990. SETTING: Hospital Universitari del Mar, a
      teaching hospital with 440 beds located in Barcelona, Catalonia, Spain.
      PARTICIPANTS: Medical records were randomly selected from records of adults
      discharged from hospital with a principal diagnosis other than normal delivery or
      any psychiatric condition. Altogether 750 records with complete data were
      reviewed for 1988 and 633 for 1990. MEASUREMENTS AND MAIN RESULTS: The
      appropriateness evaluation protocol (AEP) was used to assess whether or not the
      admission and each day of the hospital stay were appropriate. For data analysis
      we used the extension of logistic regression that allows quantification of within
      patient clustering of inactive days. The average length of stay (LOS) was 11.7
      days in 1988 and 9.5 in 1990 (p < 0.001). In contrast, the proportion of
      inappropriate admissions was 12% in 1988 and 19% in 1990 (p < 0.001). Among those
      patients who were appropriately admitted, the average odds of a given day being
      inactive in 1990 was no lower (OR = 1.09) than the odds in 1988, but the
      clustering of inactive days was significantly (p < 0.001) lower in 1990.
      CONCLUSIONS: In the hospital studied, a lower average length of stay was not
      associated with an improved level of appropriate utilisation. Policies
      exclusively focused on lowering LOS may not directly lead to a reduction in
      inappropriate hospital utilisation.

PMID- 8762387
TI  - Cost effectiveness and equity of a community based cardiovascular disease
      prevention programme in Norsjo, Sweden.
AB  - STUDY OBJECTIVE: To evaluate the cost effectiveness and equity of a community
      based cardiovascular disease prevention programme. DESIGN: A prospective cross
      sectional design. SETTING: A community based intervention to reduce
      cardiovascular disease in the district of Norsjo (n = 5500), Sweden. The
      intervention was aimed at both the general population and at individuals thought
      to be at special risk, the emphasis being on changing dietary habits and reducing
      cholesterol concentrations. PARTICIPANTS: The participants were men and women
      aged 30-60 years. MAIN RESULTS: The mean serum cholesterol concentration in the
      Norsjo population was reduced by nearly 20% during the first six years of
      intervention. It was estimated that the programme's overall total societal costs
      were 363,000 pounds and estimates of the cost per year of life saved ranged from
      14,900 pounds to net savings, according to different assumptions. Taking only
      health care costs and savings into account, the cost per year of life saved
      ranged from 1100 pounds to 4050 pounds. The results varied between different sex
      and age groups, but not between social classes. Even if a causal relationship
      exists between low cholesterol concentrations and excess mortality, the estimated
      side effects of lowering cholesterol values in Norsjo were negligible in
      comparison with the expected benefits. CONCLUSIONS: The community based
      intervention in Norsjo seems to be cost effective even under conservative
      assumptions. The approach used seems to have benefited all social classes. Cost
      effectiveness analyses that take consequences for equity into account are
      valuable tools in decision making.

PMID- 8762389
TI  - A comparison of three measures of perceived distress: results from a study of
      angina patients in general practice in Northern Ireland.
AB  - OBJECTIVE: To establish the effect of health education on the level of distress
      felt by patients with angina and to compare the results obtained using different
      measures. DESIGN: Randomised controlled trial of personal health education given
      every four months. SETTING: Eighteen general practices in the greater Belfast
      area. SUBJECTS: These comprised 688 patients aged less than 75 years and known to
      have had angina for at least six months: 342 were randomised to receive education
      and 346 no education. MAIN OUTCOME MEASURES: These were the Nottingham health
      profile (NHP), functional limitation profile (FLP), and a simple categorical
      scale (SCS). RESULTS: The intervention group showed a statistically significant
      improvement in health relative to the control group in terms of physical mobility
      and social isolation using the NHP. In terms of overall wellbeing, both the NHP
      and SCS results showed the intervention group had experienced statistically
      significant improvements in health relative to the control group. Results
      obtained using the NHP, FLP, and SCS were found to be correlated regardless of
      whether weighted or unweighted scores were used. CONCLUSION: The intervention
      produced a significant improvement in health status. Results from different
      survey instruments were correlated using both weighted and unweighted scores. An
      SCS was capable of detecting the improvement in health status.

PMID- 8762390
TI  - Hospital volume, calendar age, and short term outcomes in patients undergoing
      repair of abdominal aortic aneurysms: the Ontario experience, 1988-92.
AB  - OBJECTIVE: To determine, for abdominal aortic aneurysm surgery, whether a
      previously reported relationship between hospital case volume and mortality rate
      was observed in Ontario hospitals and to assess the potential impact of age on
      the mortality rate for elective surgery. DESIGN: Population based observational
      study using administrative data. SETTING: All Ontario hospitals where repair of
      abdominal aortic aneurysm as a primary procedure was performed during 1988-92.
      PATIENTS: These comprised 5492 patients with unruptured abdominal aortic
      aneurysms and 1203 patients with ruptured abdominal aortic aneurysms admitted to
      hospital between 1988-92 for repair of abdominal aortic aneurysm as a primary
      procedure. MAIN OUTCOMES: In-hospital death and length of in-hospital stay.
      RESULTS: The case fatality rate was 3.8% for unruptured abdominal aortic
      aneurysms and 40.0% for ruptured abdominal aortic aneurysms. For unruptured
      cases, after adjustment for patient and hospital covariates, each 10 case per
      year increase in hospital volume was related to a 6% reduction in relative odds
      of death (odds ratio (OR) 0.94, 95% confidence intervals 0.88, 0.99) and 0.29
      days reduction (95% CI -0.22, -0.35) in postoperative in-hospital stay. Female
      sex (OR 1.53, 95% CI 1.08, 2.18) and transfer from another acute care hospital
      (OR 4.37, 95% CI 2.62, 7.29) were associated with increased case fatality rates
      among patients in the unruptured category. For ruptured cases, neither the case
      fatality rate nor postoperative in-hospital stay were significantly related to
      hospital volume. The case fatality rates increased linearly and substantially
      with advancing age both for unruptured and ruptured aneurysms, and the excess
      risk of postoperative death in ruptured as compared to unruptured aneurysms was
      substantially higher in older patients. CONCLUSION: The relationship between
      hospital volume and mortality or morbidity was very modest and observed only for
      elective surgery. Case fatality rates in patients with ruptured abdominal aortic
      aneurysms remained 10 times higher than for patients with unruptured abdominal
      aortic aneurysms, despite improvements in overall mortality in comparison to
      previously published data. More effective detection of aneurysms, including
      elective repair for those once considered "high risk" older patients, might
      further reduce the toll from ruptured aortic aneurysms.

PMID- 8762391
TI  - Estimating life expectancy using an age-cohort model in Taiwan.
AB  - OBJECTIVES: Life expectation is a valuable summary index in public health and
      actuarial science. The life expectancies published in the vital statistics,
      however, are derived from the "current" rather than from the "cohort" life table.
      The former is based on a strong assumption of constant mortality in the
      population, whereas the latter calls for a recording of the mortality experience
      of a group of individuals, which is often an impossible task. Thus, a method of
      calculating cohort life expectancy without actual follow up is much needed.
      METHODS: Estimation of cohort life expectancy was based on an age-cohort model.
      Mortality data for the male population in Taiwan from 1951 to 1990 are used to
      illustrate the methodology. RESULTS: The increment of life expectancy over time
      in Taiwan is actually steeper than was previously thought using the current life
      table technique. CONCLUSIONS: The method is easy to implement and the data
      required are the usual age and period cross classified mortality data. It
      warrants further investigation.

PMID- 8762392
TI  - Agreement between the Takeda UA-731 automatic blood pressure measuring device and
      the manual mercury sphygmomanometer: an assessment under field conditions in
      Newcastle upon Tyne, UK.
AB  - STUDY OBJECTIVE: To assess agreement between two Takeda UA-731 automatic blood
      pressure measuring devices (referred to as machines A and B) and two manual
      mercury sphygmomanometers. DESIGN: A 'Y' connector attached each Takeda UA-731 to
      a manual mercury sphygmomanometer. Simultaneous measurements were made on adult
      subjects. SETTING: A population based cardiovascular disease survey in Newcastle
      upon Tyne, UK. PARTICIPANTS: Measurements on machine A were compared in 71
      individuals (all women), and on machine B in 75 individuals (9 men, 66 women).
      The age range of subjects was 28 to 76 years and median ages were 59 years for
      machine A and 50 years for machine B. MAIN RESULTS: Blood pressure (mmHg) ranged
      from 72 to 212 systolic and 44 to 102 diastolic. Both Takedas gave significantly
      lower readings than the manual devices for systolic and diastolic pressures:
      differences were mean (SD: 95% CI) 3.7 mmHg (6.5: 2.2, 5.2) for machine A
      systolic, 2.3 mmHg (4.5: 1.3, 3.4) machine A diastolic; 1.8 mmHg (6.2: 0.4, 3.3)
      machine B systolic, and 1.8 (4.4: 0.8, 2.8) machine B diastolic. On the British
      Hypertension Society criteria, machine A was graded C on systolic measurements
      and B on diastolic; machine B was graded B on both systolic and diastolic
      measurements. CONCLUSIONS: The performance of these machines compares favourably
      with the Dinamap 8100, recently adopted for survey work by the Department of
      Health. The Takeda UA-731 looks promising for epidemiological survey work but
      before it can be fully recommended further evaluations are needed.

PMID- 8762393
TI  - Two proxies for morbidity in the 1991 UK census: permanent sickness and limiting
      long term illness.

PMID- 8762394
TI  - Causes of adult female mortality in Al Ain district, United Arab Emirates.

PMID- 8762395
TI  - Caesarian sections in Guadalajara, Mexico: sociodemographic risk factors.

PMID- 8762396
TI  - Geographical variation in coronary revascularisation rates.

PMID- 8762397
TI  - Why is the sex ratio falling in England and Wales?

PMID- 8762398
TI  - Comparing measures of variation.

PMID- 8762399
TI  - Perinatal mortality in a first generation immigrant population and its relation
      to unemployment in The Netherlands.

PMID- 8762400
TI  - Shigella infections.
AB  - Shigella dysentery is a major public-health problem in many tropical areas.
      Despite improvements in water supplies and sanitation, it continues to be a
      disease of poor rural and urban communities and in populations affected by
      migration and crowding following disasters. Pathogenesis is due to colonic
      invasion, endotoxin, and, in Shigella dysenteriae 1, shiga toxin. As well as the
      local manifestations of dysentery, systemic complications include convulsions,
      haemolytic-uraemic syndrome, hyponatraemia and hypoglycaemia. The spread of
      shigella infection is most commonly person-person, although water and food-borne
      outbreaks have been reported. Since 1970, multiple antimicrobial resistance,
      particularly in Sh. dysenteriae 1, has complicated strategies for management.
      Multiply resistant strains have occurred in Latin America, Central Africa and
      southern and south-eastern Asia. No vaccines are currently available, and
      prevention and control will depend on public-health improvements and improved
      case management.

PMID- 8762401
TI  - Naphthylisoquinoline alkaloids exhibit strong growth-inhibiting activities
      against Plasmodium falciparum and P. berghei in vitro--structure-activity
      relationships of dioncophylline C.
AB  - The growth-inhibiting activities of naturally occurring naphthylisoquinoline
      alkaloids against asexual blood stages of Plasmodium falciparum (NF 54, clone
      A1A9) and P. berghei (Anka) were studied in vitro. Three of the alkaloids [7-epi
      dioncophylline A (8b), dioncolactone A (4), and 5'-O-demethyl-8-O-methyl-7
      epidioncophylline A (11)] displayed good activities against both parasites, with
      median inhibitory concentrations (IC50) of 1-5 micrograms/ml. Dioncophylline C
      (2), however, was even better, with IC50 of 0.014 microgram/ml (P. falciparum)
      and 0.015 microgram/ml (P. berghei) and therefore regarded as a promising lead
      for studies of structure-activity relationships. The free N- and 8-OH-functions
      were shown to be prerequisites for the outstanding activity of this molecule
      against P. falciparum, the presence of at least one free phenolic OH-function
      appearing to be essential for any activity. Initial experiments with derivatives
      of ancistrocladine (1) show that, in contrast to 2, N-derivatization of this
      alkaloid leads to increased activity against P. falciparum.

PMID- 8762402
TI  - Malarial infection and birthweight in urban Zanzibar, Tanzania.
AB  - In urban Zanzibar, Tanzania, 389 women with full-term pregnancies were studied to
      see what effect their infection with malaria (at delivery) had on the birthweight
      (BW) of their infants. The overall prevalence of low birthweight (LBW) (i.e. <
      2500 g) was 3.9% (15 out of 389). Overall, 21.3% (82/384) of the women only had
      peripheral parasitaemias at delivery, 17.6% (58/329) only had active placental
      infections and 47.9% (157/328) had both. The youngest women (< 20 years), the
      primiparae and those with Plasmodium infection gave birth to neonates with
      relatively low mean BW. The lowest mean BW (2967 g) was found among the offspring
      of women with active placental infection (N = 58). The women with past/chronic
      infection (N = 73) or no infection (N = 201) generally produced heavier infants,
      with mean BW of 3242 and 3338 g, respectively. The women with active placental
      infection were also far more likely to have babies of LBW (15.5%) than those with
      past/chronic infection (1.4%) or no infection (1.5%). Multivariate analysis
      indicated that the highest relative risk of LBW (10.1, with a 95% confidence
      interval of 2.9-35.4) was associated with active placental infection, with no
      significant difference between primiparae and multiparae. In the study
      population, therefore, with its low prevalence of LBW, malaria infection
      increased the risk of LBW in full-term neonates by about 10-fold, with a
      population-attributable proportion of 55.4%.

PMID- 8762403
TI  - A seroprevalence and descriptive epidemiological study of malaria among Indian
      tribes of the Amazon basin of Brazil.
AB  - Data on the seroprevalences of Plasmodium falciparum, P. vivax, and P. malariae
      in four isolated Indian tribes of the Amazon basin in Brazil, as determined by
      IFAT, were re-analysed. Age-, sex- and tribe-specific geometric mean antibody
      titres and externally standardized prevalence ratios were calculated for each
      parasite species. Correlation coefficients and prevalence odds ratios were also
      calculated for multiple infections with different combinations of the three
      Plasmodium species. Titres of all but one of the antibodies studied were similar
      in males and females; titres of antibodies to the blood stages of P. malariae
      were slightly higher in females than in males. Titres of antibodies to all three
      Plasmodium species increased with subject age, and this age effect was not
      confounded by sex or tribal differences. There were striking differences between
      tribes, with the Parakana tribe having relatively low titres of antibodies
      against P. falciparum and P. malariae; these tribal effects were not confounded
      by sex or age differences between tribes. The results indicate that conditions
      conductive to the transmission of P. malariae exist in this region of the Amazon.
      The potential for zoonotic transmission of P. brasilianum, a parasite of monkeys
      which is morphologically similar to P. malarie, and the generally high rates of
      seropositivity to all three species of Plasmodium indicate that control measures
      which are adequate and applicable to the region studied need to be developed.

PMID- 8762404
TI  - Production of monoclonal antibodies for the identification of the eggs of Taenia
      solium.
AB  - Two antibodies, one monoclonal and one polyclonal, were produced and used to
      identify Taenia solium eggs, using the enzyme-linked immuno-electrotransfer blot
      technique (EITB). Different life-stages of Taenia solium and T. saginata,
      including eggs from gravid proglottids recovered, post-treatment, from patients
      infected with the tapeworms, and eggs of Diphyllobothrium pacificum and
      Hymenolepis nana from other patients were tested with these antibodies. The
      monoclonal antibody only recognized the eggs and immature proglottids of T.
      solium. The polyclonal antibody, however, not only reacted with the eggs,
      cysticerci and immature proglottids of T. solium but also with the eggs and
      immature proglottids of T. saginata. The sensitivity and specificity of the EITB
      were both 100% using the monoclonal antibody but only 78% and 60%, respectively,
      using the polyclonal antibody. Diagnostic bands for T. solium eggs corresponded
      to proteins of 22.5 kDa using the polyclonal antibody and 22.5-37 kDa using the
      monoclonal antibody. Species-specific fluorescence was obtained with an anti-T.
      solium monoclonal antibody which bound to egg-derived oncospheres of T. solium
      but not to those of T. saginata.

PMID- 8762405
TI  - Epidemiology of intestinal taeniasis in four, rural, Guatemalan communities.
AB  - There is relatively little epidemiological information on human intestinal
      taeniasis, particularly that due to Taenia solium. The current study involved
      analysis of data collected from four, rural communities in the Department of
      Jutiapa, Guatemala, between 1991 and 1994. Overall, 92 cases of intestinal
      taeniasis were identified, giving a mean prevalence of 2.7% (92/3399). Almost all
      (98%) of the 56 worms identified to species level were T. solium. Female subjects
      were significantly more likely to be infected than males, with a relative risk of
      1.21 (95% confidence interval = 1.04-1.42; P < 0.04). Mean prevalence rose with
      age until the 30-39-year age cohort and declined thereafter. Cases were
      significantly clustered in households (P < 0.001). Most infections appeared to
      correspond to single worms. Only one multiple-worm infection was definitely
      detected, in an individual with at least seven T. solium tapeworms, all of which
      appeared to be sexually immature. To determine potential movements of infected
      subjects out of the villages, adult subjects in two of the villages were asked
      about their main place of employment; 9.7% (94/968) were recorded as working
      either in Guatemala City or the U.S.A. The possible epidemiological implications
      of these findings are discussed.

PMID- 8762406
TI  - A study of pulmonary hydatid disease in children. 1. Epidemiological and clinical
      characteristics.
AB  - Between 1980 and 1994, 244 children (aged 1-15 years) with pulmonary hydatid
      disease underwent surgery at the Emergency Medical Institute 'N. I. Pirogov',
      Sofia, Bulgaria. The number of cases/year generally increased with time. Initial
      diagnosis, based on X-rays, ultrasonography and computed tomography, was
      confirmed by immunology. Cysts were either found in the lungs alone (178 cases)
      or in the lungs and the liver, spleen, kidneys, brain and/or diaphragm (66
      cases). Most (61.1%) of the cases were boys and most cases (60.3%) were aged 8-15
      years. Most (84.8%) had also had direct or indirect contact with dogs. The
      clinical manifestations were variable but the most frequent were cough, elevated
      body temperature, adynamia, chest pain and dyspnoea.

PMID- 8762407
TI  - Patterns of infection and transmission of human schistosomiasis mansoni and
      schistosomiasis haematobium in White Nile Province, Sudan.
AB  - The overall prevalences of infection with Schistosoma mansoni, S. haematobium or
      both species among 6122 children from 27 schools in the former White Nile
      Province of Sudan (now divided into the Kosti, El Getaina, El Gebelein and El
      Duem Provinces) were 10.1%, 21.4% and 4.5%, respectively. Geometric mean egg
      counts in the pure S. mansoni and pure S. haematobium infections were 97.7 eggs/g
      faeces and 12.9 eggs/10 ml urine, respectively. There were marked differences in
      levels of endemicity between provinces and also between schools within each
      province. School-specific prevalences and intensities of infection were
      positively correlated, both for S. mansoni and for S. haematobium. Prevalences
      and intensities of infection were generally similar in male and female subjects
      and in the different age groups into which they were split (i.e. 5-9, 10-14 and
      15-19 years). Community-based surveys of all age groups in two villages showed
      typical patterns of infections with S. mansoni and S. haematobium, with indices
      peaking in those aged 10-19 years, both in males and females. Observations on
      snail-related aspects of transmission revealed that transmission of both S.
      mansoni and S. haematobium was highly focal and also seasonal, taking place
      during the hot, dry and post-rainy seasons.

PMID- 8762408
TI  - The distribution of common intestinal nematodes along an altitudinal transect in
      KwaZulu-Natal, South Africa.
AB  - In order to study the effect of climate and topography on the distribution of
      common, intestinal nematodes in schoolchildren, changes in prevalence were
      investigated along an altitudinal transect from approximately 50 m above sea
      level (asl), near the coast, to approximately 1700 m asl, in the foothills of the
      Drakensberg Mountains, KwaZulu-Natal, South Africa. These changes were related to
      several permutations of temperature, rainfall and evaporation, using univariate
      and multiple regression analyses. A total of 693 primary schoolchildren aged
      between 7 and 15 years was examined from six communities along the 150-km
      transect. Changes in the prevalence of Trichuris trichiura were significantly
      correlated with temperature-derived variables whereas those of Ascaris
      lumbricoides and Necator americanus were correlated with rainfall-derived
      variables. A total of 17 parasite species was recovered along the transect but
      polyparasitism was negatively correlated with altitude.

PMID- 8762409
TI  - Prevalence of hepatitis E virus infection in Thailand.
AB  - Hepatitis E, also known as epidemic, non-A, non-B hepatitis, is an acute,
      enteric, infectious disease. The disease is usually mild, except in pregnant
      women, who suffer a high fatality rate from fulminant hepatic failure.
      Information on the disease in Thailand is limited. The prevalence of antibodies
      to the aetiological agent, hepatitis E virus (HEV), was therefore studied, in
      various groups of subjects from several regions of this country, using commercial
      ELISA for anti-HEV IgG and IgM. The prevalence of anti-HEV IgG, which was 9%-22%
      in the adult subjects (blood donors, pregnant women, patients with acute
      hepatitis and cases seen during an outbreak of hepatitis), increased with age. It
      was relatively low in children and adolescents from Bangkok (3.6%) and in
      children from the north-east (1.8%-6.2%) and south (2.3%) of the country. Five
      (7%) of the 68 patients with acute viral hepatitis who were tested for anti-HEV
      IgM were found positive. Although these five cases had jaundice (four cases),
      diarrhoea (three) and/or dark urine (at least four cases), all of these clinical
      signs were self-limiting and had no sequelae. Given the apparently high
      prevalence of HEV infection in young adults in Thailand, control measures,
      including provision of clean water supplies and better personal sanitation and
      food hygiene, should be implemented to prevent an epidemic of the disease.

PMID- 8762410
TI  - Enterically transmitted hepatitis in Saudi Arabia: an epidemiological study.
AB  - Rates of exposure to two, enterically transmitted viruses, hepatitis E virus
      (HEV) and hepatitis A virus (HAV), were investigated among the populations of two
      areas of Saudi Arabia: Gizan (a rural area) and Riyadh (an urban area, with
      relatively good sanitation). In Riyadh, 24.7% and 1.2% of children were
      seropositive for HAV and HEV, respectively, by the age of 12 years. There was a
      sharp increase in exposure to HAV between 13 and 20 years of age (to 63.5%) and
      most (80.0%) of the subjects aged 50 years had apparently been exposed to HAV.
      Although seropositivity to HEV also increased with subject age, it only reached
      18.8% (in subjects aged > 50 years). The age-specific patterns of exposure to HAV
      and HEV in Gizan were similar to those in Riyadh but the rates of exposure were
      generally higher; mean rates of exposure to HAV and HEV were 76.3% and 14.9% in
      Gizan and 61.3% and 8.37% in Riyadh, respectively. That rates of exposure to HEV
      in Gizan were almost twice those in Riyadh emphasizes the importance of
      sanitation as an effective measure in controlling the spread of HEV in developing
      countries.

PMID- 8762411
TI  - The genital atrium as a new character for distinguishing parous and nulliparous
      Neotropical sandflies.
AB  - Changes in the appearance of the membrane delimiting the genital atrium of
      Lutzomyia migonei are described for the first time. Dissections of laboratory
      bred females at different physiological stages (i.e. on emergence, after a
      bloodmeal and after oviposition) revealed clear and constant differences between
      the membranes of the parous and nulliparous flies. The state of the membrane can
      be used as an alternative method for accurately age-grading female sandflies.
      Dissection methods and a simplified technique to prepare parts of sandflies for
      examination in a scanning electron microscope are also presented.

PMID- 8762412
TI  - Control of Culex quinquefasciatus in pit latrines, using shredded, waste
      polystyrene.
AB  - As an alternative to the use of commercially available, expanded-polystyrene
      beads, a study was made of the effectiveness of shredded, waste polystyrene
      (SWAP) for the control of Culex quinquefasciatus. The relevant physical
      properties of the SWAP were first investigated in the laboratory. Then, under
      field conditions in wet pit latrines, mosquito emergence rates were measured
      before and after application of the material. In the laboratory, when compared
      with the commercial product, the irregular shape of the SWAP particles greatly
      reduced their capacity to spread over the water surface and the interstitial air
      spaces also permitted respiration and development of mosquito larvae.
      Nevertheless, under field conditions, with careful application of the SWAP over
      the water surfaces in wet pit latrines, almost complete control of mosquito
      breeding was observed within a few days. This was sustained for 60 days, at which
      time observations were discontinued. SWAP appears to offer an effective, cheap
      and readily available alternative to the commercial product for the control of C.
      quinquefasciatus. The practicality of using it in community-based, mosquito
      control programmes warrants further study.

PMID- 8762413
TI  - Rates of major surgery by age and sex in a rural district in Kenya.
AB  - All major surgical operations performed during 1 year in Meru district, Kenya,
      were recorded. The district, with a population of 1.3 million, had five hospitals
      and two nursing homes where major surgery was performed. Over 3400 major
      operations were recorded: Caesarean section (129.0 operations/100,000
      population), tubal ligation (39.4), laparotomy (14.0), hysterectomy (5.0), open
      reduction of fracture (4.3) and hernia repair (6.3). The total major surgery rate
      was 263/100,000 year: 88/100,000 males and 434/100,000 females. Of all major
      operations, 83.5% were performed on females, the most common being Caesarean
      section, tubal ligation, laparotomy, eye or lens removal and hysterectomy. Most
      frequent major operations on males were laparotomy, eye or lens removal, hernia
      repair, gastro-intestinal surgery and prostatectomy. Most major surgery (68.1%)
      was on young and middle-aged adults; only 7.7% was performed on children aged <
      15 years even though these made up half of the population. Rates increased with
      age, and there were modest male/female differences except for very high rates of
      obstetrical surgery on young women. There is need to expand the district's
      capacity for major surgery and also to prevent more conditions requiring surgery,
      for example by improving sexual- and reproductive-health education, making family
      planning services more easily available among sexually active adolescents, and by
      initiating more aggressive prevention programmes against injuries. Although
      population-based operation rates, totally and by sex and age-group, are useful
      indicators for monitoring service output, current reporting is inadequate. One
      step towards improvement would be to require that every hospital reports,
      annually to the district level, all major operations by kind and by age and sex
      of the patient.

PMID- 8762414
TI  - Malaria in Sao Tome and Principe: prevalence and drug-susceptibility.

PMID- 8762415
TI  - [Clinical study on the effect of TCM treatment in decreasing frequency of
      peritoneal dialysis].
AB  - Traditional Chinese herbal medicine was used in combination with peritoneal
      dialysis (PD) in order to improve the renal function and reduce the frequency of
      PD. The results indicated that, after 3 months of PD+TCM, the serum BUN,
      creatinine and mean arterial pressure of therapeutic group lowered and the
      hemoglobin elevated as compared with those after 1 month of PD (P < 0.01), the
      difference of above-mentioned criteria between PD+TCM group and less frequent PD
      (LEPD) group was significant too, while there was no obvious difference in
      comparison of the PD+TCM group with regular PD group (P > 0.05). The effective
      rate and the edema cure rate of TCM+PD group were superior to the LFPD group, but
      had no evident difference as compared with the regular PD group. The results
      revealed that PD combined with TCM treatment might reduce the frequency of PD for
      the uremia patient deserved long-term PD therapy.

PMID- 8762416
TI  - [Clinical observation on effect of yiqi huoxue decoction over the left
      ventricular diastolic dysfunction].
AB  - The left ventricular diastolic function, grade of heart function and degree of
      Heart-Qi Deficiency of 52 aged patients with left ventricular diastolic
      dysfunction (LVDD) were measured by means of Doppler echocardiography and left
      ventricular impedance cardiography before and after treatment with Buqi Qiangxin
      decoction (BQQXD), a recipe of TCM for reinforcing Qi and promoting blood
      circulation. The data were compared with that of control group (15 cases) treated
      with verapamil. Results showed that 92.3% of the LVDD patients were associated
      with Heart-Qi Deficiency and 69.2% were complicated with blood stasis. After
      treated with BQQXD, the grade of heart function was elevated in 82.6%, the degree
      of Heart-Qi Deficiency was improved in 89.6% of the patients. The parameters
      reflecting the left ventricular diastolic function were all improved in different
      degree (P < 0.05-0.01), but the parameters reflecting left ventricular compliance
      were changed insignificantly (P > 0.05). It indicated that besides controlling on
      the etiological factors, the mechanism of BQQXD in treating left ventricular
      dysfunction might be related with its calcium antagonistic effect.

PMID- 8762417
TI  - [Clinical and experimental studies on zhikang oral liquid in treatment of
      hypophrenia].
AB  - The effect of Zhikang Oral Liquid (ZK) on 50 cases of hypophrenia children was
      observed and a control group of 20 cases was set. Results showed that the total
      effective rate of ZK group was 82%, it was significantly higher than that of
      control group (P < 0.01). Animal experiment revealed that ZK could improve the
      hypomnesia in learning caused by anisodine, poor memory retention caused by
      sodium nitrite and memory hypo-reproducibility caused by 40% alcohol. The results
      of clinical and experimental studies suggested that ZK could promote the
      intelligence development of child and improve the memory.

PMID- 8762418
TI  - [Clinical and experimental studies of yuyang powder in treatment of peptic
      ulcer].
AB  - Two hundreds patients of peptic ulcer diagnosed by fiber-gastroscope treated with
      Yuyang powder (YYP) was observed and compared with patient treated with
      cimetidine for control. Results showed that the curative rate of YYP on peptic
      ulcer was 88.1%, the total effective rate was 96%, similar to that of cimetidine.
      But the difference of recurrence rate (19.1% for YYP and 46% for control) between
      the two groups was very significant. Animal experiment revealed that the
      protective action of YYP with high dosis on gastric mucosa in peptic ulcer and
      gastritis was superior to that of cimetidine, its has the double effect of both
      strengthening protective factors and weakening aggressive factors of gastric
      mucosa. Acute toxicologic test indicated that YYP has no toxic effect and was
      safe in clinical practice.

PMID- 8762419
TI  - [Clinical observation of Qi deficiency syndrome in 72 patients with chronic
      obstructive pulmonary disease treated with yiqi mianyi granule].
AB  - Seventy-two patients of chronic obstructive pulmonary disease (COPD) of Qi
      deficiency syndrome with abnormal immune indices were treated with Yiqi Mianyi
      Granule (YQMYG) and the efficacy was compared with 30 cases treated with Zhenqi
      Fuzheng Granule (ZQFZG) for control. Results showed that the marked effective
      rate of symptomatic improvement of Qi Deficiency in YQMYG group was 65.3%, the
      total effective rate was 93.1%. 88.6% of the immune indices lower than normal
      were corrected and 43.7% of them were normalized, while for indices higher than
      normal the rate were 78.2% and 52.9% respectively. These results suggested that
      YQMYG could improve the symptom of Qi Deficiency markedly, strengthen the
      cellular immunity, regulate the disorder of immune function, its therapeutic
      efficacy was obviously superior to ZQFZG (P < 0.05).

PMID- 8762420
TI  - [Study on combined acupunctural and general anesthesia in pneumonectomy].
AB  - Combined acupunctural and general anesthesia in pneumonectomy were studied. The
      result showed that general anesthesia complemented with electro-acupuncture at He
      Gu (LI 4) and San Yang Luo(SJ 8) reduced amount of Fentanyl 38-85 micrograms/h
      compared with general anesthesia alone. There were no statistical difference in
      blood pressure and heart rate during the operation in every group, all of the
      SPO2 were in normal range. It was considered that acupuncture in combination with
      general anesthesia could reduce dosage of anesthetics and the inhibition of
      physiological function. It is a practical and acceptable anesthetic method by the
      surgeon and patient.

PMID- 8762421
TI  - [Effect of zhuyu huatan decoction for cellular and humoral immunity in cerebral
      hemorrhage].
AB  - Fifty-one patients of cerebral hemorrhage were observed on controlled study which
      were treated with the Zhu-Yu Hua-Tan Decoction (ZYHTD) and Western medicine. The
      results revealed that ZYHTD could reduce the serum IgG (P < 0.05), and lymphocyte
      transformation rate (P < 0.05). Meanwhile, the patient's health condition of
      treated group was better than the control group in the fields of eliminating
      brain hematoma, evaluating patients condition score in TCM and compromised
      neurologic function (P < 0.05). It is assumed that there is positive significance
      in anti-inflammatory effect and promoting the absorption of brain hematoma in the
      acute phase of cerebral hemorrhage.

PMID- 8762422
TI  - [Clinical and experimental study of faeces trogopterus on protection of gastric
      mucosa].
AB  - The cure rate of Faeces Trogopterus in treating duodenal ulcer for six weeks was
      70.59% and the total effective rate of which was 91.18%. The Shay model of rats
      was used. The result revealed that Faeces Trogopterus could protect the gastric
      mucosa. These results preliminarily indicated the mechanism of this drug was
      inhibiting gastric secretion and regulating gastric mucosal blood flow so as to
      enhance mucosal defense.

PMID- 8762423
TI  - [Study on the effect and mechanism of qinggan xiehuo decoction in treatment of
      endotoxin-induced uveitis in rabbits].
AB  - The therapeutic efficacy of Qinggan Xiehuo Decoction (QGXHD) on rabbit model of
      uveitis (1) The symptoms of Liver-Fire such as conjunctival congestion, thirsty
      dark urine, oliguria, irritability and rapid pulse were markedly relieved (P <
      0.05-0.01); (2) The ophthalmic signs, iris hyperemia and aqueous humor turbidity
      observed through slit-lamp were improved significantly (P < 0.01); (3) The
      inflammatory infiltration, the protein content and leukocyte count in the aqueous
      humor decreased markedly (P < 0.01); (4) The concentration of inflammatory
      mediators in blood and aqueous humor were reduced. (5) Pathological examination
      showed that the QGXHD could protect the capillary, blood-aqueous barrier and
      alleviated the uveal damage caused by endotoxin.

PMID- 8762424
TI  - [Effect of Chinese herbal medicine of tonifying kidney on M-cholinergic receptor
      and acetylcholinesterase activity in dementia mimetic mice].
AB  - Dementia mimetic mouse model was formed with aluminum chloride solution in order
      to study the effect of Chinese herbal medicine of tonifying Kidney (TK) on the M
      cholinergic receptor (Rt) and the acetylcholinesterase (AchE) activity in the
      model's cerebral cortex. Results showed that the M-cholinergic receptor Rt
      lowered and the AchE increased in the model evidently as compared with the
      healthy young mice. The TK could markedly reduce the increased AchE and elevate
      the lowered M-cholinergic receptor Rt in cerebral cortex of the dementia mimetic
      mice, it also could improve the memory. These results suggest that TK is
      effective in preventing the degeneration of cerebral function and presenile
      dementia.

PMID- 8762425
TI  - [Experimental study on zhuanggu shengbao in preventing hormone-induced
      osteoporosis of rats].
AB  - Twenty four male Sprague-Dawley rats at 3 months of age were divided randomly
      into 3 groups. Prednisone acetate was given to the group B twice per weeks,
      Zhuanggu Shengbao (ZGSB) was added to the group C besides prednisone, the group A
      was control. The histomorphometric parameters of bone slides of proximal tibia
      were measured and calculated with image pattern analyser after 3 months of
      medication. Results showed that in comparing with group A, in group B the area
      and number of trabecula decreased, the intertrabecular space increased due to the
      bone resorption exceeded the bone formation, and the symptoms of osteoporosis
      revealed obviously. However, in group C, the bone resorption rate was markedly
      inhibited, and the formation of new bone accelerated so that the bone mass
      increased significantly. These results indicated the ZGSB could prevent the
      osteoporosis induced by prednisone acetate.

PMID- 8762426
TI  - [Remote effect of Tripterygium wilfordii and chlorambucil on the function of sex
      glands of child with nephropathy].

PMID- 8762427
TI  - [Analogy method for the extended use and mechanism research of xilei powder].

PMID- 8762428
TI  - [Progress in the studies on traditional Chinese medicine syndrome differentiation
      of chronic glomerulonephritis with laboratory findings].

PMID- 8762429
TI  - [Detection of EB virus in pulmonary carcinoma by in situ hybridization].
AB  - To observe the distribution of Epstein-Barr virus (EBV) in pulmonary carcinoma,
      87 cases of pulmonary carcinoma were used to detect EBV infection by in situ
      hybridization. The positive rate of EBV infection in carcinoma tissue and
      peripheral lung tissue were 37.9% (33/87) and 11.5% (10/87) respectively. The
      existence of EBV was related to both the degree of carcinoma differentiation and
      lymphocyte infiltration. The EBV positive rates and hybridization signals in the
      groups of moderately and poorly differentiated carcinoma were significantly
      higher and stronger than those in the group of well differentiated carcinoma. The
      degree of lymphocyte infiltration increased with the increase of EBV positive
      rate. These results indicate that there is a relationship between EBV infection
      and the biological features of cancer, and that EBV may play a role in the
      pathogenesis of pulmonary carcinoma.

PMID- 8762430
TI  - [A study of the association between EBV and B-cell lymphoma].
AB  - Extensive studies have demonstrated that Epstein-Barr virus (EBV) is associated
      with Burkitt's lymphoma, immunodeficiency related lymphoma, Hodgkin's disease and
      T-cell lymphoma. In order to investigate whether an association exists between
      EBV and B-cell lymphoma in patients without overt immunodeficiency, we examined
      127 B-cell lymphomas without overt immunodeficiency for expression of EBV-encoded
      small RNA (EBER-1) using RNA/RNA in situ hybridization. EBER-1 expression was
      found in nuclei of tumor cells in 8 of 127 cases (6.3%) of B-cell lymphomas. This
      result is similar to that of studies in Europe and the United States (about 5%).
      The low frequency of EBV in B-cell lymphomas suggests that EBV does not pay an
      important role in the pathogenesis of B-cell lymphomas without overt
      immunodeficiency.

PMID- 8762431
TI  - [A study of P53 protein expression in fibrous neoplasms].
AB  - An immunohistochemical method utilizing microwave oven treated avidin-biotin
      complex (ABC) technique was used in this study to detect P53 protein expression
      in 87 parafin-embedded fibrous neoplasm tissues. The results showed that the
      total positive staining rate was 20.7%. The positive staining rate in fibroma
      (FA), dermatofibrosarcoma protuberans (DFSP) fibrosarcoma (FS) and malignant
      fibrous histiocytoma (MFH) were 0%, 4.0%, 37.5% and 62.5% respectively. The
      positive staining rate of P53 protein was increased with the increase in
      malignancy of the neoplasma. The expression of P53 protein was not correlated
      with the subtypes of DFSP and MFH, but correlated with cell differentiation.
      Therefore, detection of P53 protein expression may have significant value in the
      evaluation of malignancy, metastatic potential and the prognosis of fibrous
      neoplasma.

PMID- 8762432
TI  - [Histopathological and immunohistochemical studies on gliosarcoma].
AB  - Immunohistochemical staining of 5 gliosarcomas was performed. Neoplastic glial
      component stained positive by GFAP. Endothelial cells lining the lumina of
      glomeruloid vascular structures stained positively with both UEA-1 and FVIII/RAg
      antibodies. Mesenchymal cells of sarcomatous areas stained positively with SMSA
      antibody and presence of PDGFR. The staining results demonstrate that the
      sarcomatous component of gliosarcoma is of smooth muscle origin and suggest that
      the vascular smooth muscle hyperplasia is related to PDGF.

PMID- 8762433
TI  - [Reversal of malignant phenotype of cells of human pancreatic adenocarcinoma cell
      line by recombinant retroviral vector expressing antisense c-myc].
AB  - A recombinant retroviral vector expressing antisense c-myc was constructed. The
      recombinant virus DNA was packaged with packaging cell line PA317 cells by the
      calcium phosphate coprecipitation method. The virus supernatant was used to
      infect human pancreatic carcinoma cell line PC-2. After selection with G418,
      resistant colonies were obtained. Stable expression of retrovirus in both PA317
      and PC-2 cells were confirmed by Northern blot hybridization. A down-regulation
      of endogenous c-myc was found in PC-2 cells infected with antisense c-myc
      construct. It was demonstrated that the antisense c-myc did inhibit the cell
      growth rate and 3H-TdR incorporation rate of PC-2 cells. The ability of colony
      formation in soft agar and tumorogenicity in nude mice of PC-2 cells were
      significantly suppressed by the antisense c-myc. The results implicate that
      recombinant retroviral vector containing antisense c-myc could inhibit target
      gene expression and partly reverse malignant phenotype of pancreatic
      adenocarcinoma cells.

PMID- 8762434
TI  - [In vitro transformation of human embryonic nasopharyngeal epithelial cells with
      Epstein-Barr virus].
AB  - EBV from B95-8 cells were used to infect directly the human embryonic
      nasopharyngeal epithelial (HENE) cells in vitro. RESULTS: Primary HENE cells
      treated with EBV did not have a significantly increased colony-forming rate in
      soft agarose, while cells that were treated with EBV in combination with tumor
      promotor 12-O-tetradecanoylphorbol-13 acetate (TPA) showed a marked increase in
      colonyforming rate from 0-5 cells to 20-40 colonies per 10,000 cells. (2) HENE
      cells treated with inactivated (56 degrees C for 30 minutes) virus, in spite of
      adding TPA at the same time, did not significantly increase agarose colony
      forming rate; (3) HENE cells treated with TPA after EBV exposure for a week had
      significantly increased colony forming rate in soft agarose, while the cells
      exposed to EBV after using TPA treatment did not. In addition, EBV BNLF1 (LMP)
      fragment in HENE cells treated with EBV or EBV+TPA was detected by polymerase
      chain reaction using specific oligonucleotide primer. Only HENE cells treated
      with EBV+TPA presented positive band in aragose gel electrophoresis. The results
      suggest that transformation of EBV on HENE cells depends on infectious virus and
      an intact viral genome. TPA not only can promote the transformation, but also
      promote EBV's entering HENE cells.

PMID- 8762435
TI  - [Reexpression of nerve growth factor receptor in human traumatized spinal cord].
AB  - The reexpression of nerve growth factor receptor (NGFR) on paraffin sections of
      the human spinal cord was examined with immunohistochemical method in 18 cases
      with survival periods from 2 hours to 28 months after a traumatic injury. The
      results are as follows: The reexpression of NGFR in motor neurons of the ventral
      horn began on the fourth day, which gradually decreased 30 days post trauma.
      However, it could be observed in cases with survival periods up to 28 months. The
      axons in funiculus dorsalis reexpressed NGFR 7 hours to 9 weeks after trauma
      occurred, which may be interpreted as axoplasmic transport effect of NGFR in the
      spinal ganglion cells. NGFR labelled intraspinal microvessels were present in the
      injured spinal cord. Reexpression of NGFR in motor neurons after trauma reflects
      an increased demand of neuotrophic factors to support the post trauma survival of
      NGF dependent neurons.

PMID- 8762436
TI  - [Expression of LIF as autocrinal growth factor in human medulloblastomas].
AB  - In this study, in vivo and in vitro expression of LIF and its signal transducer
      genes, LIFR and gp130 in medulloblastoma cells and its role(s) in the cell
      proliferation were investigated by different approaches. The results revealed
      that 12 out of 13 cases examined were found to express LIF and more than 90% of
      the samples to express LIFR and gp130. Functional evaluation of LIF using Med-3
      cells showed that the cell growth and DNA synthesis could be efficiently
      inhibited (P < 0.001) by neutralization of LIF bioactivity. Our data thus
      demonstrated the importance of LIF as autocrtinal growth factor in the
      proliferation of medulloblastoma cells and also implicated a potential new
      therapeutic approach for a better treatment of the tumors through blockage of LIF
      gene expression and/or ligand interaction.

PMID- 8762437
TI  - [Detection of hepatitis C virus RNA in paraffin embedded liver tissues by in situ
      PCR].
AB  - The new technique of in situ polymerase chain reaction (ISPCR) was used to study
      hepatitis C virus (HCV). ISPCR and in situ hybridization (ISH) were performed to
      detect HCV in 7 paraffin embedded liver tissues and 8 para-hepatocellular cancer
      tissues. The positive rates were 6/7 and 4/8 respectively, significantly higher
      than results obtained by ISH, which were 3/7 and 1/8 respectively. It also
      demonstrated that the specificity of ISPCR was better than ISH. HCV RNA was not
      only found in hepatocyte plasma but also in cholangiolar epithelia and monocytes.
      We conclude that ISPCR is a sensitive and specific method that can improve the
      accuracy in diagnosis of HCV.

PMID- 8762438
TI  - [Angiomatoid malignant fibrous histiocytoma].
AB  - By clinical, pathologic and immunohistochemical study on aniomatoid malignant
      fibrous histiocytoma, which is a relatively uncommon soft tissue tumor described
      by Enzinger in 1979, and often misdiagnosed, we are reporting 32 cases of this
      lesion. The distinctive histopathology were: (1) Cystic change filled with
      hemorrhagic fluid or blood, (2) surrounded by nests of fibroblastlike and
      histocyte-like cells and (3) intermingled with chronic inflammatory cells, (4)
      often surrounded by a fibrous pseudocapsule. Immunohistochemical staining done in
      4 cases showed all to be positive in lysozyme, three positive in Mac 387 and CD
      68. These results support their histiocytic origin. Follow-up information was
      available in 25 of 32 cases. All the 25 patients were alive, 4 with recurrence
      (16%), 1 with metastasis (4%). These results concur with the opinion that
      intrinsically, this is a low grade tumor.

PMID- 8762439
TI  - [Establishment and characterization of a model of highly metastatic human ovarian
      cancer transplanted subcutaneously into nude mice].
AB  - A model of highly metastatic human ovarian cancer transplanted subcutaneously
      into nude mice was established (NMSO). Although the NMSO transplanted tumors were
      passaged 23 times, they retained their highly metastatic behavior. A total of 57
      adult Balc/c nude mice (8-14 weeks old) were inoculated (SC) with tumor, the
      transplantations were 100% successful and the average survival period was 159.9
      days. 47 mice were dissected and 42 mice were found to have metastatic tumors.
      The earliest appearance of metastasis was 56 dys. 18 male nude mice all had
      metastasis. Histology and ultrastructure showed that the metastatic tumors
      retained their malignant features and secreting function of the original poorly
      differentiated human ovarian serous papillary cystadenocarcinoma. FCM analysis
      gave a 1.4 DNA index and the chromosome mode number was 54 (hyper-diploid),
      exhibiting the features of human carcinoma. The detection of correlative label
      material showed that most cancer cells were ER and PR positive. The use of NMSO
      model may lead to better understanding of the mechanism of metastasis and help
      search for anti-metastatic agents.

PMID- 8762441
TI  - [Expression of PCNA and protooncogenes during experimental hepatocarcinogenesis
      in rats].
AB  - The expression of PCNA and the protooncogenes of ras family (N-ras, H-ras and Ki
      ras) in hepatocarcinoma cells and the proliferating liver cells in precancerous,
      hyperplastic nodules during experimental hepatocarcinogenesis, induced by
      diethylnitrosamine in rat liver was observed immunohistochemically and by in situ
      hybridization. The results indicated that there was a positive expression of PCNA
      in both the carcinomas cells and precancerous liver cells. The amount of PCNA
      positive cells exhibited a negative correlation with the amount of infiltrating
      mast cells surrounding carcinoma cell nests and the hyperplastic, precancerous
      nodules. These results basically coincided with that of the separate observation
      of the expression of protooncogenes in the same study.

PMID- 8762440
TI  - [Studies on the immunopathogenesis of experimental tubulointerstitial nephritis
      in Wistar rats].
AB  - Tubulointerstitial nephritis (TIN) model was successfully induced in female
      Wistar rats by immunization with rabbit tubular basement membrane (TBM) etc. By
      using immunohistochemistry and computer assisted image processing,
      characterization of mononuclear cells in the TIN models were determined, and the
      relationship between Ia antigen expression of renal tissue and TIN studied. The
      results showed: TIN was characterized by deposition of IgG in a linear pattern
      along TBM and mononuclear cells infiltrates, which suggests the production of
      anti-TBM antibodies. Among the mononuclear cells, most are T cells. Granuloma
      formation was observed in parts of TIN. B cells gradually decreased while
      monocytes gradually increased. The renal tissue lesions show tubular atrophy and
      peritubular fibrosis. This model strongly suggests that cellular immune responses
      play an important role in the development of TIN. Ia antigen expression is higher
      in cells of the tubular epithelium and Bowman's capsule of lesion site than in
      control group (P < 0.01). This is strong evidence that the abnormal expression of
      Ia antigen may be affected by the production and development of TIN.

PMID- 8762442
TI  - [Vomiting, night sweating and paralysis of bilateral extremities].

PMID- 8762443
TI  - [Characterization of outward current in mouse ventricular myocytes].
AB  - Depolarization-activated, calcium-independent outward currents (Iout) in
      enzymatically dispersed mouse ventricular myocytes were characterized by whole
      cell recording technique. During brief depolarizations to potentials positive to 
      50 mV, outward K+ currents in these cells rise rapidly to a peak followed by a
      slower decay to an apparent plateau. The relative peak to plateau amplitudes in a
      single cell varied as a function of the holding potential (HP) from which the
      currents were evoked. Reversal potentials for the peak and plateau components
      were -64.3 +/- 3.9 mV and -53.3 +/- 2.9 mV, respectively (uncorrected for
      junction potentials). The outward current decay is well described by double
      exponential fits, whereas the time course of peak Iout decay following a 500 ms
      prepulse is best fitted by single exponential function, indicating the presence
      of two distinct components, IKf and IKs, of the outward currents in mouse
      ventricular cells. Application of 4-AP were accompanied by a marked attenuation
      of peak Iout and plateau Iout, indicating that both IKf and IKs display similar
      sensitivities to 4-AP. The steady state inactivation of IKf is found incomplete
      within the test potential range (-80 - +30 mV) owing probably to the fact that
      the APD of mouse myocardium is too short.

PMID- 8762444
TI  - [Tumor necrosis factor induced enhancement of neutrophil chemotaxis and adhesion
      through mediating of phospholipase A2 activation].
AB  - Recent studies indicate that phospholipase A2 (PLA2) derived lipid mediators
      regulate a number of neutrophil responses such as chemotaxis, adhesion and
      degranulation. Since tumor necrosis factor (TNF) is also a key mediator in
      neutrophil activation, it remains to be shown that PLA2 is involved in the
      process of TNF activation. Our results shown that TNF (100 ng/ml) given in vitro
      for 60 min, causes an obvious enhancement of neutrophil chemotaxis towards FMLP,
      and increased activity of adhesion to glass beads by stimulated release of TXB2
      from PMN other than 6-keto-PGF1a. Similar neutrophil activation responses could
      also be promoted by in vitro addition of arachidonic acid (1 mumol/ml) for 60
      min. It was further found that PLA2 inhibitor, 4-bromophencyl bromide (5
      mumol/ml), greatly inhibite the TNF induced responces, while cycloxgenase
      inhibitor indomethathin (85 nmol/ml) was without effect on the activation of TNF.
      Those results indicated that PLA2 activation was involved in the TNF stimulated
      enhancement of neutrophil chemotaxis and adhesion.

PMID- 8762445
TI  - [Experimental analysis of the calcium source for cardiac excitation-contraction
      coupling in hibernator Citellus dauricus].
AB  - The force-interval and force-frequency relationships and the effects of Cd2+ and
      ryanodine on the myocardial action potential and contraction were compared
      between hibernating (HGS) and active (AGS) ground squirrels Citellus dauricus.
      (1) Raising the driving frequency caused a negative inotropic effect in the AGS
      group, but a biphasic change with an increase of the peak force followed by a
      decrease in the HGS group. The contraction in HGS group exhibited a more
      pronounced post-interval potentiation, and was more significantly modulated by
      the driving frequency. (2) HGS animals displaged action potentials of shorter
      early-stage duration and stronger contractions of shorter time course in
      comparison with the AGS animals. Both the action potential and the contraction of
      HGS group were less affected by Cd2+, but the contraction was more significantly
      inhibited by ryanodine than that of the AGS group. Our results suggested that
      dependence of cardiac excitation-contraction coupling on calcium influx was
      weakened, while the function of sarcoplasmic reticulum as a source of activator
      Ca2+ was enhanced during hibernation, which might take an important part in the
      cold-tolerant adaptation of hibernating hearts.

PMID- 8762446
TI  - [Reduction of incidence of ischemia-reperfusion induced ventricular fibrillation
      by captopril].
AB  - To investigate the role of catecholamine and prostacyclin in ischemia reperfusion
      induced ventricular fibrillation, experiments were performed in rat hearts using
      methods of radioimmunoassay and fluorohistochemistry. Regional myocardial
      ischemia was induced by ligation of the left coronary artery followed by
      reperfusion. In the ischemia reperfusion group, ventricular fibrillation during
      reperfusion took place in 78% of the hearts. In the group pretreated with
      captopril, the incidence of ventricular fibrillation decreased significantly
      (65.5%). In comparison with the ischemia reperfusion group, myocardial
      catecholamine content and 6-keto-PGF1 alpha of the captopril group were
      significantly increased (P < 0.01) while thromboxane B2 (TxB2) and TxB2/6-keto
      PGF1 alpha were decreased (P < 0.01). In Ang II group, infusion of angiotensin II
      reversed the protective effect of captopril and restored the incidence of
      ventricular fibrillation (85%), while myocardial catecholamine content was not
      different from the ischemia reperfusion group (P > 0.05). Above results suggest
      that reduction of the incidence of ischemia reperfusion-induced ventricular
      fibrillation by captopril may be due to its inhibition on angiotensin II
      production with consequent reduction of the release of myocardial catecholamine,
      suppression of TxB2 and promotion of PGI2 synthesis.

PMID- 8762447
TI  - [Hypoxia induced increase of MDA and echinocytes from erythrocytes in rabbit's
      blood with special reference to inhibition of the increase by MPEG-SOD].
AB  - When rabbits acutely exposed to hypobaric hypoxia (at imitative altitude 5,000 m,
      PaO2 = 6.7 kPa), the percentage of the activity of superoxide dismutase (SOD in
      erythrocyte; EC 1.15.1.1) decreased respectively to 86%, 76%, 81%, 84%, 55%, 81%,
      84% and 95% for a period of 0.25, 0.5, 1, 2, 3, 4, 5 and 24 h hypoxia while MDA
      (malondialdehyde) in erythrocyte and plasma increased significantly during
      hypoxia periods of 1, 2, 3, 5 and 24 h (n = 5, P < 0.05, P < 0.01 vs. normoxia
      group). The increase of MDA in plasma could be prevented by vitamin E (V. E, i.p,
      1 mg daily for 3 consecative days before hypoxia), but that in erythrocyte did
      not show significant change probably because the injected V.E. without vehicle
      cannot penetrate through the erythrocyte membrane effectively. The echinocytes
      from erythrocytes increased significantly after hypoxia for 24 h (n = 5, P < 0.05
      vs. normoxia group). However, by injecting MPEG-SOD (monomethoxypolythlene glycol
      SOD) intravenously 30 min before hypoxia, the increase of MDA (both of
      erythrocyte and plasma) and echinocytes (from erythrocytes) were both inhibited
      obviously during hypoxia for 24 h (n = 5, P < 0.05, P < 0.01 vs. hypoxia group).
      It is inferred that the increase of MDA and echinocytes from erythrocytes may be
      due to lipid peroxidation by superoxide free radicals (O2-.) generated in
      erythrocytes through Fenton pattern Haber-Weiss reaction during hypobaric
      hypoxia.

PMID- 8762448
TI  - [Effects of some physical and chemical factors on CGRP release from mesenteric
      arterial bed].
AB  - We have shown that calcitonin gene-related peptide (CGRP) is released into the
      circulation during endotoxin or hemorrhagic shock. In the present study, it was
      observed that low pH, elevated levels of lactic acid, hypertonic NaCl and
      hypertonic sucrose caused CGRP release from isolated mesenteric arterial bed
      (MAB) of rat. All the responses were blocked when MAB was pretreated with
      capsaicin. Ruthenium red, an inhibitor of Ca(2+)-induced Ca2+ release from
      intracellular Ca2+ pools, significantly inhibited the release of CGRP. In Ca2+
      free medium, low pH, lactic acid and hypertonic solutions became no longer
      capable of inducing the release of CGRP. The above results suggest that the
      observed release of CGRP in MAB was mediated by capsaicin-sensitive sensory nerve
      endings, as a result of Ca(2+)-induced Ca2+ release from the intracellular Ca2+
      store which is sensitive to ruthenium red.

PMID- 8762449
TI  - [The effect of renal dopamtne receptor blockade on natriuresis induced by volume
      expansion and intracerebroventricular injection of hypertonic saline in rabbits].
AB  - The present study was carried out to study the effects of renal dopamine receptor
      blockade on natriuresis induced by volume expansion (VE) and
      intracerebroventricular injection of hypertonic saline (ICHNa) in connexion with
      the use of dopamine receptor blockers haloperidol (Hal) in anesthetized rabbits.
      In the VE experiments, Hal group decreases the peak increase of UNa V from
      control group of 65.0 +/- 15.0 to 19.0 +/- 5.5 mumol/min (P < 0.02). In the ICHNa
      experiments, the peak increase of UNa V in control and Hal groups were
      respectively 28.9 +/- 4.6 and 29.0 +/- 5.8 mumol/min (P > 0.50). In the
      experiments of rabbit with intact renal dopamine receptor, the natriuresis
      induced by VE+ICHNa was significantly greater than those due to either inducing
      factor acting alone. Renal dopamine receptor blockade also significantly
      attenuated the natriuresis induced by VE+ICHNa. These results indicate that renal
      dopamine receptor blockade significantly attenuated the natriuresis induced by VE
      or VE+ICHNa, but did not affect the response of ICHNa. In the rabbits with intact
      renal dopamine receptor, the natriuretic response induced by VE+ICHNa was
      significantly greater than those response by either inducing factor acting alone.

PMID- 8762450
TI  - [The effects of single administration of kainic acid on cellular signal
      transmission pathway and susceptibility to seizure].
AB  - In this study, Sprague-Dawley (S.D.) rats were pretreated with kainic acid (KA,
      10 mg/kg, i. sc.) 72 days before either deep prepyriform cortex (DPC) kindling or
      injection of the same dose of KA. The results showed that such pretreatment
      accelerated the process of kindling, and the KA-induced seizures appeared more
      severe in behaviours. c-Fos-immunoreactivity (c-Fos-ir) was used to demonstrate
      the neuronal activity in central nervous system during the provocative dose of KA
      induced seizure, as comparing with the control which received normal saline of KA
      72 days ago. The results indicated that, the transmission pathways in two groups
      were just the same; but the time courses of c-fos and c-jun expression in KA
      pretreated group were accelerated asynchronously; and the synthesis of the
      proenkephalin mRNA in the Ent was apparently up-regulated. It is suggested that,
      the long-lasting increase in susceptibility to seizure induced by a single
      administration of KA may be related to the acceleration of the expression of c
      fos/jun and the early onset of the expression of proenkephalin mRNA.

PMID- 8762451
TI  - [Excitation of hypothalamic nucleus arcuatus neuron induced decrease of plasma
      sialic acid level in rats].
AB  - The effect of sodium glutamate (Glu) on plasma sialic acid (SA) level was studied
      by means of microinjection into the nucleus arcuatus (ARC) and ultraviolet
      spectrophotometry. The results indicate: (1) The plasma SA level was
      significantly decreased after microinjection of Glu into the ARC (P < 0.01). With
      increasing Glu concentration, the onset of the decrease occurred earlier. (2)
      When Glu was microinjected into ARC after intraventricular injection of
      apomorphine, the plasma SA level was significantly decreased (P < 0.01) and the
      time required to cause the decrease was shortened. (3) When Glu was microinjected
      into ARC after intraventricular injection of spiperone, no change was found in
      the plasma SA level (P > 0.05). The above results suggest that the mechanism
      underlying the decrease of plasma SA level is probably related to modulated
      dopamine (DA) release of hypothalamic dopaminergic neurons by DA-D2 receptor.

PMID- 8762452
TI  - [Effects of (-) SPD and (-) THP on the firing of noradrenergic neurons in locus
      coeruleus].
AB  - The effects of (-) SPD and (-) THP on the noradrenergic neurons in rat locus
      coeruleus were investigated by recording the in vivo spontaneous firing. It was
      found that (-) SPD could increase the firing frequency of the NE neurons via
      antagonistic action on alpha 2 autoreceptors in a dose-dependent manner, while
      alpha 2 receptor agonist clonidine exerted an inhibitory effect. (-) THP induced
      inhibitory firing of the neurons, however, irreversible.

PMID- 8762453
TI  - [Central mechanism of an extensive analgesic effect due to strong
      electroacupuncture of acupoint on spinal dorsal horn neurons].
AB  - Experiments were performed on male rats. The responses of dorsal horn convergent
      neurons in spinal cord (T12-L1) to noxious stimulation of hind paw were recorded
      extracellularly with glass microelectrode. When low intensity (2 V)
      electroacupuncture (EA) was used, the nociceptive responses of convergent neurons
      were inhibited by EA at "Zusanli" near noxious stimulation area, but not at
      "Xiaguan" far from the area. When intensity (18 V) high than the threshold of C
      fibers EA was applied at the far acupoint "Xiaguan", obvious analgesic effects on
      convergent neurons were also produced, showing an extensive analgesic effect of
      strong EA at acupoint. This extensive analgesic effect was abdicated by lesion of
      nucleus raphe magnus (NRM), but still persisted to some extent by EA at the same
      segment acupoint "Zusanli" with 18 V or 2 V intensity. The results suggest that,
      the extensive analgesia of strong EA at far segment acupoint may be mainly
      mediated by noxious stimulation through NRM, a negative feedback mechanism
      modulating pain of supraspinal cord. The analgesia due to 2 V EA at the same
      segment acupoint may be mainly produced by gate control in spinal cord, but also
      to some extend by supraspinal cord mechanism.

PMID- 8762454
TI  - [Changes of opioid contents in brain and plasma through the hibernation bout
      cycle of ground squirrels-].
AB  - Measurements of beta-endorphin (beta-EP) and Met-enkephalin (MEK) contents in
      various brain areas and plasma of ground squirrels were carried out by
      radioimmunoassay (RIA) through euthermia, entrance, deep hibernation and arousal
      phases of natural hibernation bout. The main results showed that, the beta-EP
      content in hypothalamus and pituitary during the entrance phase were increased
      and further deepened during deep hibernation, whereas in hippocampus and plasma
      the tendency of the changes of beta-EP content took place in an opposite
      direction, i.e. being lowered down from the euthermia level upon entering the
      entrance and deep hibernation phase. The content in pons and medulla showed
      little change through the bout. The contents of MEK were increased during
      entrance and lowered when entering into deep hibernation to different extent in
      different brain areas, being most significant change has taken place in
      hippocampus. These results indicated that the role of beta-EP and MEK in
      hibernation was different both in regard to brain regional changes of their
      content and in the degree of the changes.

PMID- 8762455
TI  - [Induction of expression of MDR 1 gene by retinoic acid and DMSO and effects on
      rhodamine-123 efflux in HL-60 cell lines and resistant sublines].
AB  - Using dot blot hybridization and flowcytometry, the effects of differentiation
      inducers retinoic acid (RA) and dimethyl sulfoxide (DMSO) on the resistant level
      of HL-60 cells and its resistant subline cells were studied. When the cells were
      treated with RA 1 mumol.L-1 for 24 h, the expression of MDR 1 mRNA evidently
      increased in both HL-60 and its multidrug resistant subline cells. The efflux of
      Rho-123 in the multidrug resistant subline cells was slightly decreased. But,
      when the cells were treated with 2% DMSO for 24 h the efflux of Rho-123 increased
      obviously. The results suggest that RA can induce the expression of MDR1 gene but
      perhaps inhibit the function of pump glycoprotein 170 (Pgp-170) through
      phosphorylation/dephosphorylation pathway. However, DMSO could induce the
      expression of full function of Pgp.

PMID- 8762456
TI  - [Beneficial effects of acetylsalvianolic acid A on focal cerebral ischemic rats
      subjected to middle cerebral artery thrombosis].
AB  - Acetylsalvianolic acid A (ASAA) is a semisynthetic analogue of salvianolic acid A
      isolated from Danshen (Salvia miltiorrhiza Bunge). A rat middle cerebral artery
      thrombosis model was made by adding FeCl3 to the surface of the right middle
      cerebral artery (MCA). Using this model, the protective effects of ASAA on focal
      cerebral ischemic injury were studied. The neurologic status of each rat was
      carefully evaluated at 4, 8 and 24 h after surgery. The cerebral infarction and
      the morphological changes of brain tissue were examined. Pretreatment with ASAA
      50 or 100 mg.kg-1 iv was shown to significantly reduce the cerebral infarction
      and attenuate neurological deficits. The degree of inhibition of cerebral
      infarction were 46.5% (P < 0.05) and 87.4% (P < 0.01), respectively. In
      pathological examination, pretreatment with ASAA 100 mg.kg-1 iv, there was no
      thrombosis or only a little thrombosis in MCA. The extent of tissue ischemia was
      much less than that of control. These results indicate that the beneficial
      effects of ASAA on focal cerebral ischemic rats subjected to middle cerebral
      artery thrombosis may be related to its antithrombotic effect.

PMID- 8762457
TI  - [Effect of (+), (-) and (+/-) gossypol on early pregnancy in rats].
AB  - Treatment of rats with (+/-) gossypol 80 mg.kg-1 or (-) gossypol 40 mg.kg-1 on
      day 6-9 of gestation terminated early pregnancy. However, (+) gossypol at the
      dosage of 40 mg.kg-1 was found to have no effect on gestation. (-) Gossypol at a
      concentration of 30 micrograms.ml-1 showed an inhibitory effect on progesterone
      production and (+) gossypol at 10 micrograms.ml-1 caused an increase of
      progesterone secretion by luteal cells in vitro. A marked increase of
      progesterone level in granulosa cells was elicited by hCG. The steroidogenic
      response of granulosa cells to hCG was inhibited by (+/-) gossypol at 10 and 30
      micrograms.ml-1.

PMID- 8762458
TI  - [Effect of dl-3-n-butylphthalide (NBP) on purine metabolites in striatum
      extracellular fluid in four-vessel occlusion rats].
AB  - The effects of NBP on concentrations of some purine metabolites in extracellular
      fluid of rat striatum during global ischemia and reperfusion were studied. Global
      ischemia was produced by the four-vessel occlusion method. Push-pull cannula was
      implanted stereotaxically into the striatum of rat and was perfused with Ringer's
      solution at a flow rate of 2.5 microliters.min-1. The level of adenosine(Ade),
      inosine(Ino), hypoxanthine(Hyp) and xanthine(Xan) in perfusates were measured
      with HPLC connected with a UV detector. The results indicate that the levels of
      ade, ino, hyp and xan were significantly increased (about 3-5 times of initial
      value) during cerebral ischemia and reperfusion. NBP at the dose of 20 or 40
      mg.kg-1 given intra-peritoneally 20 min before ischemia was shown to depress the
      increase of ade, ino, hyp and xan during ischemia and reperfusion dose
      dependently. But no change in the level of purine metabolites was found in sham
      operated rats. It has been known that harmful free radicals were produced when
      xan and uric acid were formed by xanthine oxidase during reperfusion. This might
      be important for the development of ischemic injuries. Our findings suggest that
      the effect of NBP might be beneficial for protection against post-ischemic
      neuronal damage.

PMID- 8762459
TI  - [Effect of dl-3-n-butylphthalide (NBP) on life span and neurological deficit in
      SHRsp rats].
AB  - Effects of NBP on liability of stroke, life span and neurological deficits
      following stroke were studied in stroke prone spontaneously hypertensive rats
      (SHRsp). The SHRsp rat was kept on 1% NaCl solution as drinking water and was fed
      15 g soft food containing 0.6-0.8 g NaCl per day. Total NaCl intake for one rat
      was 1.1-1.3 g per day. After the onset of stroke, tap water and normal food was
      given instead of that containing NaCl. The neurological deficits were evaluated
      by a specially designed scoring system. These symptoms were divided into 4
      degrees (1-4). Grade 1. stress (mild). Grade 2. forelimb or head twitch or with
      stress (severe). Grade 3. hemiparalysis, body inclined or disabled. Grade 4.
      paralysis, tremor or convulsion. Blood pressure, heart rate and body weight were
      measured once every 2 weeks. The weights of heart, brain and kidneys were also
      measured. The results show that NBP pre-treatment at the dose of 100 mg.kg-1.d-1
      po delayed the onset of stroke. So, like nimodipine, NBP showed a stroke
      preventive action in SHRsp rats. In addition, treatment with NBP 100 mg.kg-1.d-1
      po after the onset of stroke, the life span was prolonged and the score of
      neurological deficit decreased significantly. Because high blood pressure can not
      be lowered by NBP treatment, therefore, the protective effect against stroke can
      not be explained by the effect of hypotension. No change was found in BP, HR and
      the organ weight. The results indicate that NBP is expected to be useful in the
      treatment of stroke.

PMID- 8762460
TI  - [Effect of enhancers on the permeation of ketoprofen in vitro].
AB  - The result of permeability test of ketoprofen (KP) in vitro showed that the
      penetration process could be described by zero-order kinetics. Azone (AZ), oleic
      acid (OA), 1-methyl-2-pyrrolidone (2P), dimethylformamide (DMF), propylene glycol
      (PG) and lauryl alcohol (LA), six penetration enhancers, on the percutaneous
      absorption of KP were carried out by using isolated shaved mouse skin. These
      enhancers exhibited different effects. Among the enhancers, OA, AZ, 2P and PG
      enhanced the skin permeation of KP. Their order of effect was OA > AZ > 2P > PG.
      AZ and 2P in combination with OA were shown to have synergistic effect. But DMF,
      LA and PG at high levels inhibited the permeation of KP.

PMID- 8762461
TI  - [Studies on ethmozine sustained-release tablet remaining-floating in stomach].
AB  - An oral sustained-release system of ethmozine (E-HBS) was developed. The in vitro
      release characteristics of E-HBS were shown primarily to be of the first order of
      kinetics (Kr = 0.2436 h-1). The gamma-scintiphotographic study showed that E-HBS
      remained in the human stomach for more than 6 hours after ingestion, much longer
      than the conventional tablet (1-1.5 h). The plasma concentration-time curve of E
      HBS exhibited typical sustained-release characteristics. The percentage of drug
      released in vitro vs the percentage of drug release in vivo of E-HBS indicated
      excellent linearity.

PMID- 8762462
TI  - Inhibition of [3H] flunitrazepam binding to rat brain membranes in vitro by
      puerarin and daidzein.
AB  - Compounds acting on the central nervous system (CNS) have been isolated and
      identified from plants used for medicinal purposes. Radix Puerariae is used in
      Chinese traditional medicine for the treatment of drunkenness and alcoholic
      addiction. Benzodiazepine tranquilizers exert their pharmacological effects by
      modulating the efficacy of the inhibitory neurotransmitter gamma-aminobutyric
      acid (GABA) at the GABA/benzodiazepine-chloride channel complex in the brain.
      Since some of the pharmacological effects of ethanol are thought to be mediated
      via the GABA/benzodiazepine-chloride channel complex, we investigated if extracts
      from Radix Puerariae contain active substances at the benzodiazepine receptor
      which could explain its reported usefulness for medical purposes. Therefore, a
      bioassay-guided purification of active substances from Radix Puerariae was
      initiated.

PMID- 8762463
TI  - [The photolytical products of aqueous carboplatin solution].
AB  - Carboplatin, an abbreviation for 1, 1-cyclobutanedicarboxylatodiamine platinum
      (II), is the second generation platinum anticancer drug. The stability of its
      aqueous solution is of great importance to clinical effects. It has been known
      that the solution is relatively stable with t1/2 being about three months when
      kept in dark place, and unstable to light as shown by the rapid change in the UV
      spectrum. But, the photolytic products remain unidentified. As a knowledge of the
      products plays an important role in understanding the influence of photolysis of
      carboplatin on the clinical effects, we have recently studied the photolytical
      products of aqueous carboplatin solution upon 313 and 254 nm irradiation, and now
      report our results here.

PMID- 8762464
TI  - [Advances in the research on tyrosine protein kinase inhibitors].

PMID- 8762466
TI  - [The immunomodulatory effect of lentinan].
AB  - Lentinan (LTN) was extracted from Lentinus edodes (Berk) Sing with molecular
      weight of 5 x 10(5). The effects of lentinan on cellular immune function were
      studied in vivo by measuring the cellular delayed type hypersensitivity (DTH) to
      dinitrofluorobenzene (DNFB) in cyclophosphamide (Cy)-comprised mice. The effect
      of lentinan on T lymphocyte proliferation to Con A on splenocytes and T
      lymphocyte subpopulations on thymocytes and on splenocytes from normal mice were
      also evaluated. Moreover, the effect of LTN on production of tumor necrosis
      factor (TNF) from murine peritoneal macrophage was also tested. LTN was
      administered at doses of 1, 5 and 10 mg.kg-1.d-1. The following results were
      observed: LTN administration(X6) augmented the T lymphocyts proliferation to Con
      A in normal mice; LTN restorated the DTH to DNFB impaired by single Cy(200 mg.kg
      1 and 80 mg.kg-1, ip) after using LTN for 8 or 5 d; LTN administration (X6)
      either decreased the percentage of L3T4+ (Th), Lyt2+ (Ts) in thymocytes or
      increased the percentage of L3T4+, Lyt2+ in splenocytes; LTN(X6) administration
      elicited release of TNF from M phi in the presence of lipoplysaccharide (LPS).
      These results indicate that the immunomodulating effect of LTN may be relevant to
      change of T cell subpopulation and increase of TNF production.

PMID- 8762465
TI  - [Population pharmacokinetics/pharmacodynamics of magnesium sulfate in pregnancy
      induced hypertensive gravidas treated with the drug].
AB  - NONMEM program was applied for analyzing population
      pharmacokinetics/pharmacodynamics of magnesium sulfate in pregnancy induced
      hypertensive patients treated with the drug. A 2-compartment open model with fast
      and slow consecutive intravenous infusion was used to estimate population
      pharmacokinetics from 60 patients. A 3-compartment model comprised an effect
      compartment linked to the central compartment, sigmoid Emax effect model and
      parametric method were used to estimate population pharmacodynamic parameters
      from 26 patients. Serum magnesium concentration was determined by
      spectrophotometric method ant it was adjusted with basic value determined before
      dosage. The diastolic blood pressure lowering effect was chosen as index of
      effect of cardiovascular response. The population pharmacokinetic parameters of
      magnesium sulfate were: the standard value of K10(h-1), K12(h-1), K21(h-1), and
      Vc(L.kg-1) were estimated to be 1.62, 20.8, 2.70, and 27.0, respectively. Their
      interindividual varibilities were estimated to be 25.70%, 14.13%, 24.33%, and
      34.04%, respectively. The residual error of concentrations was 15.03%. The
      population pharmacodynamic parameters of magnesium sulfate were: the standard
      value of Emax (%), Ce(50) (microgram.ml-1), upsilon, and Keo (h-1) were estimated
      to be 28.73, 28.39, 4.22, and 0.43. Their interindividual variability were
      estimated to be 56.32%, 62.24%, 33.47% and 42.76%. The residual error of effect
      was 28.54%.

PMID- 8762467
TI  - [Antagonism of piracetam on the amnestic effect of diazepam in mice].
AB  - In step-down test, diazepam (1 mg.kg-1 po, 1 h before training) was shown to
      significantly impair memory acquisition in mice. But piracetam (200 mg.kg-1 ip, 1
      h before training) was found to improve the diazepam-induced impairments of
      learning. By photocell cage method, piracetam showed no significant inhibitory
      effect on the diazepam-induced spontaneous motor activity in mice. In Y-maze
      test, Glutamic acid (0.1 microgram, icv, 3 min before training) significantly
      improved learning in normal mice and the amnesic effect of GABA and diazepam were
      completely antagonized by Glutamic acid and piracetam (200 mg.kg-1 ip, 1 h before
      training). These results suggest that increasing GABA-ergic neuronal transmission
      is unfavorable to learning and memory, but increasing Glu-ergic transmission is
      contrary to the former. It seemed that the presence of Glu/GABA system in the
      brain could regulate learning and memory.

PMID- 8762468
TI  - [Studies on the mechanisms of immunoregulatory effects of ginsenoside Rg1 in aged
      rats].
AB  - Using methods of fluorescence flow cytometry and Western blot analysis, Rg1 was
      found to enhance the expression of IL-2 receptor alpha chain and inhibit the
      release of soluble IL-2 receptor. In in vitro experiment, Rg1 showed no influence
      on Con A-induced increase of cytoplasmic free calcium concentration, but
      significantly increased the levels of intracellular cAMP and cGMP in aged
      animals. In view of the important role of cAMP and cGMP as second messengers in
      the regulation of immune system, the results of the present studies suggest that
      one of the mechanisms by which Rg1 enhances immune function in old rats might be
      mediated by increase of cAMP and cGMP contents, resulting in IL-2 gene expression
      and splenocyte proliferation.

PMID- 8762469
TI  - [Effect of dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2, 2'
      dicarboxylate (DDB) on several phenotypes of Bel-7402 hepatocarcinoma cell line
      and its mechanism].
AB  - DDB is a hepatoprotectant and has been widely used for the treatment of chronic
      viral hepatitis in China. The drug markedly improved the abnormal liver function
      particularly in lowering the elevated serum transaminases in patients. It is
      known that there is a close correlation between primary hepatocarcinoma and
      chronic viral hepatitis. The aim of the present study is to evaluate the effect
      of DDB on hepatocarcinoma cell line. The results showed that the growth and
      clonogenicity of Bel-7402 human hepatocarcinoma cell line cultured with DDB were
      markedly inhibited. The nucleoles of the cells treated with DDB disappeared or
      their numbers and nucleus/cytoplasm ratio decreased under electron microscopic
      observation. DDB at the concentration of 10(-4) mol.L-1 significantly increased
      the contents of cAMP and calmodulin (CaM) in Bel-7402 hepatocarcinoma cells. DDB
      was also found to inhibit topoisomerase II activity of Bel-7402 hepatocarcinoma
      cells. These results suggest that the mechanism of inhibition of DDB on several
      phenotypes of Bel-7402 cell line may be related to its effect on cAMP and CaM
      content as well as topoisomerase II activity.

PMID- 8762470
TI  - [Synthesis and activities of fragments of inhibin alpha subunit].
AB  - For further investigation of inhibin which is available only by laborious
      isolation, four fragments of inhibin alpha subunit (7-28, 37-65, 1-32, Y-1-32)
      were prepared by solid phase peptide synthesis using the Fmoc strategy. The
      effects of these fragments on progesterone production of rat corpus luteal (CL)
      cells in vitro were examined. The results indicate that these four fragments
      induced significant decrease of basic progesterone production.

PMID- 8762471
TI  - [Determination of amikacin by single oscillopolarography in the presence of
      formaldehyde].
AB  - The singlescan oscillopolarographic behavior of formaldehyde derivative of
      amikacin (AMK) in the medium of Britton-Robinson buffer solution (pH 8.0) has
      been studied and the mechanism of its electrode process has been discussed. Under
      optimum conditions, the peak current increases linearly with the increase of AMK
      concentration in the range of 6.0 x 10(-7)-5.0 x 10(-5) mol.L-1 and its
      correlation coefficient is 0.9988. The detection limit is 2.4 x 10(-7) mol.L-1.
      This method has been applied to the determination of trace AMK in samples of its
      injection, urine and blood serum without pretreatment. Its recovery was 90%-100%
      and the relative standard deviation was less than 4.1%.

PMID- 8762472
TI  - [Studies on gelatin microsphere loaded ligustrazine hydrochloride for lung
      targeting].
AB  - The effect of ligustrazine hydrochloride (LTH) on depressing pulmonary artery
      hypertension has been proved in recent studies. In an attempt to prepare a lung
      targeting dosage form, ligustrazine hydrochloride gelatin microspheres (LTH-GMS)
      were prepared by the method of emulsion process, using 2:1 as the weight ratio of
      LTH to gelatin. The preparation technique was optimized and the appearance,
      particle size and size distribution, LTH content, in vitro release, stability,
      and in vivo distribution of LTH-GMS were studied. The results showed that the
      mean diameter of LTH-GMS measured by Coulter counter was 12.65 microns, 87.5% of
      the microspheres ranging from 5 to 24.9 microns. The average content of LTH in
      LTH-GMS was 16.49% +/- 0.49% (n = 3) with an average extent of entrapment of
      about 89% and the LTH-GMS were stable for three months when stored in
      refrigerator or at room temperature. The release profile in vitro (pH 7.8-8.0
      phosphate buffer) can be described by first-order kinetic equation. The release
      t1/2 of LTH when given LTH-GMS was about 6 times as much as that of original LTH.
      The relative distribution percentage of LTH-GMS in lung when determined 20 min
      after iv administration to mice was significantly higher than those of LTH-GMS in
      other tissues and blood, and was about 6 times as much as that of the LTH
      solution control group in lung under the same conditions.

PMID- 8762473
TI  - [Rapid detection of Salmonella with MUCAP reagent].
AB  - The 4-methylumbelliferyl-caprylate (MUCAP) was applied for the identification of
      Salmonella, it's specification, sensitity, and availability were reported. 65
      strains of standard Salmonella, 48 strains of Salmonella isolated from foods
      growing on plates of HE, DHL, SS and MaConkey agar have been tested with MUCAP.
      All of them were identified as MUCAP positive; whereas, among the non-Salmonella
      tested only Pseudamonas spp., Aeromonas hydrophilia and Plesiomonas shigelloides
      were shown as positive, but they could be differentiated easily with Salmonella
      by means of oxidase test. The unspecific reaction of Serratia marcescens could be
      eliminated by using the plate medium which has been added of 1% sucrose. Both the
      sensitivity and specificity of the method were up to 97% more, and the operating
      of the method was very facility and to be done within few minutes.

PMID- 8762474
TI  - [Construction of shuttle vector containing delta-endotoxin gene of Bacillus
      thuringiensis].
AB  - The Bacillus thuringiensis toxin gene CryIA(c) was inserted into the shuttle
      vector pBE-2 to construct pAMY for expressing the B.t. gene in both Gram-negative
      and -positive bacterial systems. pAMY was introduced into wild type Bacillus
      cereus, B.brevis and B.subtilis by electroporation. Transformants containing
      delta-endotoxin gene produced proteins reacted with B.t. crystal protein
      antibody. Upon biological toxicity tests, the transformants gave a mortality of
      100% against Ostrinia furnacilis, 58.8% against Heliothis armigera and 100%
      against Heliothis assulta. The ability of promoting plant growth of the original
      strains is retained.

PMID- 8762475
TI  - [Preparation of beta-1,3-glucan synthase and its application to the screening of
      antifungal antibiotics].
AB  - beta-1,3-glucan synthase was obtained as a particulate fraction from cell-free
      extracts prepared after mechanical breakage cells of Candida albicans. Some
      properties of the glucan synthase were investigated. Using it as a target for
      screening for novel antifungal compounds, we obtained strains whose products
      showed differential enzyme inhibition.

PMID- 8762476
TI  - [Recognizing drug-induced lung injury].

PMID- 8762477
TI  - [Progress in oncogenes and anti-cancer genes in lung cancer].

PMID- 8762478
TI  - [Gene therapy in lung cancer].

PMID- 8762479
TI  - [Detection of K-ras oncogene activation in human lung cancer and its possible
      clinical application].
AB  - By using a modified polymerase chain reaction (PCR) and restriction fragment
      length polymorphism (RFLP) technique, we detected K-ras codon 12 mutation in 102
      formalin-fixed, paraffin-embedded tissues from surgical samples of lung cancer
      patients. The X2 test was used to determine the statistical significance of
      difference, according to the presence or absence of mutation in codon 12 of K-ras
      oncogene. We found 25 cases (24%) positive for mutation of K-ras 12 codon.
      Mutation occurred in 6 of the 40 cases (15%) of squamous cell carcinoma, 18 of 37
      adenocarcinoma cases (49%), 1 of 2 adenosquamous cases, 0 of 1 carcinoid patient,
      but no K-ras activation was found in small cell carcinoma (0/22) cases. Analysis
      of the clinical and pathological features of 37 adenocarcinoma cases showed no
      apparent associations between the K-ras codon 12 mutation and sex, disease stage,
      tumor size (T), metastatic status (M) and the degree of differentiation (all P
      values greater than 0.05), but the nodes (N) of K-ras-positive adenocarcinoma
      tended to be more than the K-ras-negative ones (P < 0.01). From 26 male cases of
      adenocarcinoma mutation in codon 12 of K-ras occur more frequently in
      adenocarcinoma from smokers than non-smokers (P < 0.05), suggesting that smoking
      is an important factor in the induction of the mutation. Among 37 adenocarcinoma
      cases, only 25 cases can be traced the recurrence rate in 1-year. The 1-year
      recurrence rates were 85% (11/13) in K-ras mutational patients, more than 25%
      (3/12) in K-ras negative ones (P < 0.01), whereas there was no relationship
      between recurrence and differentiation in these 25 cases. The findings suggest
      the K-ras gene mutation may be one of the prognostic markers for human lung
      adenocarcinoma.

PMID- 8762481
TI  - [The effect of transforming growth factor-beta on collagen expression by human
      embryonic fibroblasts].
AB  - Transforming growth factor-beta (TGF-beta) is a cytokine with diverse biological
      activity. It can regulate the metabolic function of extracellular matrix (ECM)
      and play an important role in the development of pulmonary fibrosis. Collagen are
      major ECM components that are responsible for normal lung structure and function.
      Collagen accumulation is a major feature of pulmonary fibrosis. In order to study
      the mechanism of pulmonary fibrosis, we examined the effects of TGF-beta on the
      production, mRNA expression of type I collagen and type IV collagen by cultures
      of human embryonic lung fibroblasts. The results indicated that TGF-beta can
      induce collagen formation and type I collagen, type IV collagen mRNA expression
      without affecting cell proliferation. We concluded that TGF-beta plays a role in
      collagen accumulation of pulmonary fibrosis and the changes in collagen
      production appear to be mediated on collagen mRNA level.

PMID- 8762480
TI  - [T antigen test of sputum--a new simple method for the screening of lung cancer].
AB  - The sputum specimens from 116 healthy persons and 216 cases of benign and
      malignant lung diseases were detected for T antigen using a strip test by enzyme
      galactose oxidase-Schiff sequence. The result shows that 165 cases of the 182
      patients with lung cancer, confirmed by cytology and histology, had positive
      results, whereas 22/116 (19.0%) of healthy controls were positive. So the
      sensitivity was 90.7% and the specificity was 81.0%. In 28 cases of patients
      whose cytology of sputa showed various degrees of dysplasia, 21 were found T
      antigen positive, of which 15 patients were identified to be lung cancer in the
      follow-up study. In addition, three cases of early lung cancer in this study were
      also positive, suggesting that T antigen was expressed at an earlier stage in the
      malignant process. The study has indicated that T antigen test of sputum is a
      sensitive method for the diagnosis of lung cancer. It may also be a promising
      approach for the massive screening of lung cancer in terms of its rapidity,
      economy and simplicity.

PMID- 8762483
TI  - [Measurement of respiratory muscle performance in patients with chronic
      obstructive pulmonary disease].
AB  - Respiratory muscle performance is measured in terms of strength and endurance. A
      RMSE-1 type measuring system for evaluation of respiratory muscle strength (RMS)
      and endurance (RME) has been developed and tested in normal subjects and patients
      with stable chronic obstructive pulmonary disease (COPD). The results showed that
      there was no significant difference between normal subjects and stable COPD
      patients in RMS measured as maximum inspiratory pressure (MIP) and maximum
      expiratory pressure (MEP). The maximum load (Load(m)), mean mouth pressure at
      maximum load (Pmean), and the maximum sustainable inspiratory pressure (SIP(m))
      as % MIP (SIP(m)/MIP) were taken as measure of RME. All measures of RME in COPD
      group were much lower than those in the normal. The measurement of RME can be
      used to evaluate the effect of respiratory muscle training and direct the
      respiratory rehabilitation in COPD patients.

PMID- 8762482
TI  - [The role of endothelin the development of hypoxic pulmonary hypertension].
AB  - To evaluate the role of endothelin in the development of hypoxic pulmonary
      hypertension, seven pigs (50 +/- 5kg) models with hypoxia induced pulmonary
      hypertension were established. Swan-Ganz catheter and arterial catheter were
      inserted into the pulmonary artery and aorta, pulmonary arterial pressure (PAP),
      pulmonary capillary wedge pressure (PCWP), cardiac output (CO) and arterial blood
      gases were monitored before and during hypoxia and 5 min, 30 min, 60 min, 120 min
      after nitrendipine injected (100 micrograms/kg). Plasma endothelin concentration
      was measured by RIA. It was found that plasma ET concentration was significantly
      increased, from 5.5 +/- 1.1 ng/L during normoxia to 11.9 +/- 1.2 ng/L during
      hypoxia (PaO2 = 5.55 +/- 0.24 kPa) (P < 0.002), while PAP increased from 3.88 +/-
      0.10 kPa to 5.92 +/- 0.19 kPa. After nitrendipine injection, PAP and ET level
      were decreased by 1.03 kPa (P < 0.05) and 40% (P < 0.02) respectively compared
      with those with pure hypoxia. Our results indicate that ET may play an important
      role in the development of hypoxia induced pulmonary hypertension. Ca++-channel
      blocker nitrendipine not only relieves hypoxic pulmonary hypertension, but also
      inhibits the release of endothelin.

PMID- 8762484
TI  - [Investigation of the application of electrical impedance principle for the
      diagnosis of diaphragm fatigue].
AB  - We designed and performed the chest and abdomen impedance respirograph (IRG),
      which included the one dimentional IRG and the two dimentional IRG, by applying
      the principle of bioelectrical impedance. Using IRG, we measured the non
      synchronized chest and abdomen respiratory motions occurring in the diaphragmatic
      fatigue. The results showed that all 203 normal control subjects showed
      synchronized pattern of chest and abdomen respiratory motions. In 189 COPD
      patients 117 (61.9%) showed non-synchronized respiratory motions which could be
      further divided into three types: type I showed complete contradirectional
      movements of respiration, M > 24% and alpha angle > 120 degrees; type II showed
      staggered peak of the chest and abdomen motion curves, 13% < M < 24%, 50 degrees
      < alpha angle < 120 degrees; type III showed double peaks in the one dimentional
      IRG and 8-shaped double circles in the two dimentional IRG, M < 13%, alpha angle
      > 40 degrees. When compared with Pdi and diaphragm myoelectricity frequency
      spectrum the rates of accordance were 81.8% and 90%, respectivity, suggesting
      that IRG could be reliably used to diagnose diaphragmatic fatigue. This technique
      is simple, easy, cheap and non-invasive. It is, therefore, worth to be widely
      recommanded for clinical investigation.

PMID- 8762485
TI  - [The changes in collagen contents and its clinical significance in chronic
      obstructive pulmonary disease].
AB  - Type III procollagen (P IIIP) hyaluronic acid (HA) and fibronectin (Fn) were
      assayed in patients with COPD, with radio-immunoassay (RIA). The results were
      shown as follows: The mean levels of P IIIP, HA were significantly higher than
      those of normal (P < 0.05, < 0.05). Plasma Fn was consistantly in lower level in
      COPD (P < 0.05). It is suggested that P IIIP, HA and Fn played a role in
      development of pulmonary fibrosis and quantification of such collagen contents
      may be a sensitive index to assess the degree of pulmonary fibrosis and to
      predict the prognosis of patients with COPD.

PMID- 8762486
TI  - [A research of acute hemodynamics and hormonal changes of intravenous captopril
      in patients with cor pulmonale and pulmonary hypertension].
AB  - In 20 patients of cor pulmonale with heart failure and respiratory failure and in
      11 healthy men, after intravenous captopril injection, acute hemodynamic and
      hormonal change were observed. The results indicated that intravenous captopril
      injection rapidly reduced cardiac preload and afterload, reduced pulmonary
      arterial pressure, increased cardiac output, inhibited renin system activity,
      decreased plasma level of thyroxin and atrial natriuretic peptide. A rapid
      symptomatic improvement in patients with acute or severe cor pulmonale was shown
      and there was no significant effect on blood gas immediately.

PMID- 8762487
TI  - [Effect of inhaled corticosteroids on serum eosinophil cationic protein and sIL
      2R levels in asthmatics pulmonary hypertension].
AB  - To study the influence of corticosteroid and beta 2-agonist on eosinophil and T
      lymphocyte functioning state in the asthmatics, we measured the serum ECP sIL-2R
      levels and airway reactivity before and after 6-week treatment with beclometasone
      and terbutalin. The result revealed that after inhalation of steroid, the serum
      ECP sIL-2R levels decreased, whereas the lung function improved and MCH-PC20
      values increased. It suggested that steroid could inhibit activation of
      eosinophil and T lymphocyte as well as show the effect of anti-inflammation and
      reducing AHR.

PMID- 8762488
TI  - [A three-year retrospective cohort study on pulmonary tuberculosis in Shanghai.
      Shanghai Pulmonary Tuberculosis Epidemiological Research Group].
AB  - Based upon the study population selected for a cross-sectional survey in 1990, a
      three-year retrospective cohort study on pulmonary tuberculosis was carried out
      in Shanghai. The cases of tuberculosis from 1987 to 1990 were determined
      according to home-visit inquiry combined with medical history collection,
      physical examination and routine notification material. The overall incidences of
      active, bacillus positive and smear positive for the whole city, higher in male
      than in female, were 54.5/100,000, 21.5/100,000 and 19.4/100,000, respectively.
      The incidence tended to rise with the increase of age, and, there were peaks
      among age group 30 and 60. The initial and relapse incidences were 48.7/100,000
      and 5.8/100,000, and most of the relapse cases were those aged above 45. The
      undetection rates of active, bacillus positive and smear positive were 23.1%,
      36.6% and 37.8%, respectively. The registration rate of detected cases was above
      97%. This study indicates that it is applicable to perform retrospective cohort
      study on tuberculosis while conducting cross-sectional survey and the data can be
      used to evaluate the epidemiologic situation, control effect and the quality of
      notification.

PMID- 8762489
TI  - [Guinea pigs infected by bacterial dust aerosol of Bacillus tuberculosis].
AB  - There still is controversy over whether Bacillus tuberculosis could be spread by
      dust. For the purpose to illustrate the possible contagious route, guinea pigs
      were exposed to bacterial dust aerosol which was generated by mixing Bacillus
      tuberculosis H37Rv with dried dust. The percentage of the size of particles,
      diameter < 4 microns, was 5.1%. The density of bacteria in the dust aerosol was
      386.7 cfu/L and the mass medium diameter (MMD) was 1.9 microns. On the 70 days
      after exposure, in the 3 minutes exposed group, positive reaction to OT test
      (1:20) was 2/7, culture of Bacillus tuberculosis was positive from lungs and
      spleen was 1/7, in the 18 minutes exposed group, 5/8 were positive for OT test,
      the positive culture found from lungs was 2/8 and from spleen 1/8. These results
      showed that Bacillus tuberculosis could be spread by bacterial aerosol.

PMID- 8762490
TI  - [Fifteen years' experience in reformed Beijing tuberculosis control programme].
AB  - Since 1978 a new tuberculosis control programme based on WHO recommended modern
      concept has been started in Beijing. A sound network of tuberculosis control
      service has been organized. Fully supervised intermittent chemotherapy with newly
      diagnosed cases of smear-positive pulmonary tuberculosis as top priority has
      achieved satisfactory high rates of compliance and sputum conversion in all 18
      districts and counties of the city. Sputum examination was emphasized as the main
      tool for diagnosis and determination of criterion of cure. Drugs are provided
      free to those who are needy. On the basis of good implementation of fully
      supervised chemotherapy for newly diagnosed smear-positive cases, fully
      supervised retreatment for chronic infectious cases was started, and it resulted
      in a rapid reduction of the prevalence of chronic infectious tuberculosis from
      69.9 in 1979 to 6 in 1985 per 100,000. The prevalence of smear-positive
      tuberculosis of Beijing during the 3 National Surveys of Tuberculosis was 127, 56
      and 16 per 100,000 in 1979, 1985 and 1990 respectively, with an average annual
      reduction rate of 17%.

PMID- 8762491
TI  - [Determination of tuberculostearic acid for diagnosis of tuberculous meningitis
      with negative culture of tubercle bacillus].
AB  - Tuberculostearic acid, a structural component of Mycobacterium tuberculosis, was
      identified by gas chromatography in cerebrospinal fluid from 44 out of 59
      patients with tuberculous meningitis. Tuberculostearic acid was found in the
      cerebrospinal fluid of 5 patients out of 112 with non-tuberculous meningitis or
      non-infectious disorders. The results showed the test had a sensitivity of 74.6%
      and a specificity of 95.9%. Detection of tuberculostearic acid in cerebrospinal
      fluid is a rapid, sensitive and specific test for tuberculous meningitis.

PMID- 8762492
TI  - [Comparative experiment of gas chromatography determination of Mycobacterium
      bacillus].
AB  - Using capillary column gas chromatography (GC) technique for detecting cellular
      fatty acid, the test of the GC chromatograms of 26 reference Mycobacteria strains
      (freeze-dried strains and transfer growed strains at the improved Lowenstein
      Jensen culture for three or four weeks) was performed. On the basis of the test,
      a comparison was made between the GC method and the conventional method for
      determination of 54 strains of non-tuberculous mycobacteria which were separated
      from clinical specimens, and the conformational rate of the two methods was 94
      percent. At the same time, the relationship between the drug resistance and the
      changes of GC chromatograms of M. tuberculosis and M. bovis which were separated
      from clinical samples was observed. The results demonstrated that the GC method
      would achieve better results if combined with the bacterial growing speed, the
      condition of producing colour and the condition of growing at PNB and TCH culture
      during determining the mycobacterium strains which were separated from clinical
      specimens.

PMID- 8762493
TI  - [Four cases of similar Hexheimer's reaction during the initial chemotherapy for
      tuberculosis bacillus].
AB  - In the report, 4 patients with similar Hexheimer's reaction during initial
      chemotherapy for pulmonary tuberculosis were presented. The literatures on
      clinical manifestations, predisposing factors, pathogenic mechanism, pathological
      changes, diagnosis and management of Hexheimer's reaction are reviewed.

PMID- 8762495
TI  - [A radiographic classification for sarcoidosis based on the ILP/UC classification
      bacillus].
AB  - A scheme was devised for semiquantitative description of 79 cases with
      sarcoidosis using the graphic terminology of International Labour Office and
      Union International Contre Le Cancer (ILO/CU) for the pneumoconioses. Among 56
      patients with stage II, "linear-irregular" categories s t u (50%) and
      "reticulonodular" categories x y z (28%) predominated while "rounded" categories
      p q r (22%) were unusual. Among 13 patients with stage III s t u and x y z
      opacities were found in 38% of patients while p q r only in 23%. The opacities in
      both stages of sarcoidosis were most severe in the bilateral lower lobes. It was
      concluded that the traditional method for classification of sarcoidosis was
      helpful to give the qualitative diagnosis of the disease, but it did not provide
      objective description of the type and degree of pulmonary involvement. ILO/UC
      classification was an important supplement of traditional method as ILO/UC could
      be used to grade the type (linear irregular, rounded and reticulonodular
      opacities), severity and location of opacities. Therefore, the two methods should
      be used in combination so as to judge the location, type and severity of
      intrathoricic sarcoidosis.

PMID- 8762494
TI  - [The effect of anti basic fibroblast growth factor on the development of
      experimental silicosis bacillus].
AB  - Anti-bFGF serum was used to treat rabbit experimental silicosis. At 90 days, when
      experimental group was compared with control group, the number and size of the
      nodules in experimental group were much less and smaller than those in control
      group. Nodules in control group were mainly consist of fibroblast mixed with a
      small amount of collagen fiber, whereas nodules in experimental group were made
      up of macrophages. At 180 days, in addition to fibroblasts, there was II to III
      degree of collagen fiber in nodules of control group. Most of nodules in
      experimental group mainly contained macrophages. Fibroblasts of lung in fetal
      mice were cultured in vitro. The results showed that bFGF stimulated
      proliferation of fibroblast, whereas anti-bFGF serum inhibited fibroblast growth.
      It appeared that anti-bFGF serum actually blocked proliferation of fibroblast and
      fibrosis in rabbit experimental silicosis.

PMID- 8762496
TI  - [The clinical significance of Pseudomonas aeruginosa typing and R-plasmid and DNA
      molecule hybridization in patients with cor pulmonale].
AB  - 600 strains of Pa were typed from the sputa of patients with cor pulmonale in 8
      hospitals. P6 type stoods first, accounting for 25.6%, and the types of PA and
      the difference in distribution of Pseudomonas from different districts and
      hospitals, might be used as an important parameter in the epidemiological study.
      68 of 150 strains from patients with cor pulmonale contained plasmids. 60
      isolates harboring plasmids colonies were hybridized with 6 beta-lactamase and 6
      aminoglycoside modifying enzyme resistance gene probes. The experiments
      demonstrated the 3 strains isolated from patients with nosocomial infection came
      from one same strain and got a new resistance gene during spreading of nosocomial
      infection, and these isolates contained homologous sequence with OXA-2 and AAC
      (6')-1b probes.

PMID- 8762497
TI  - [Correlation between roentgenogram and CT scans with the changes of cells in
      bronchoalveolar lavage fluid in sarcoidosis].
AB  - Considering protean and variability of chest findings of sarcoidosis, the
      correlation between finding on roentgenogram and CT scans with changes of total,
      differential cell count and subsets of lymphocytes of BALF in 25 cases with
      sarcoidosis was studied. The results showed that CT could detect more groups of
      enlarged lymph nodes in the mediastinum and more minimal lesions in lung
      parenchyma in those patients who showed stage 0 and I on chest roentgenogram. The
      parenchymal changes were distributed mainly among the bronchovascular sheath.
      Good correlation was found between findings on CT scan and total cell count in
      BALF. Fibrotic changes on CT scan were usually associated with an increase in
      neutrophils of BALF. It indicated that CT could more precisely assess the lesions
      in the mediastinum and lung parenchyma and be served as an important
      supplementary diagnostic measure to roentgenogram for patients with sarcoidosis.

PMID- 8762498
TI  - [The comparison of positive rates and clinical significance of 8 bronchodilator
      testing parameters sarcoidosis].
AB  - Twenty asthmatic patients (with mild to severe attacks) were examined with
      bronchodilator test. Eight parameters, FVC, FEV1, PEF, FEF25-75%, FEF25-75% after
      inhaling bronchodilator (FEF25-75% Iso), thoracic gas volume (Vtg), airway
      resistance (Raw) and specific conductance (SGaw), were investigated, compared and
      analysed. The results showed that the positive rate (PR) of FEV1, the most
      commonly used parameter at present, was only 70%; the PR of two new parameters
      FEF 25-75% Iso and SGaw were 95% respectively, the change rate (%) of FEV1 was
      significantly related to that of many other parameters. The pathophysiology and
      clinical significance of each parameter were discussed.

PMID- 8762499
TI  - [The role of endothelin-1 and tumor necrosis factor-alpha in the development of
      asthma sarcoidosis].
AB  - In order to investigate the interaction of endothelin-1 (ET-1) and tumor necrosis
      factor-alpha (TNF-alpha) and their activity in the pathogenesis of asthma, ET-1
      plasma and BALF levels were measured, and the amount of TNF-alpha released from
      alveolar macrophage (AM) was also tested. As in vitro the airway smooth muscle
      cells were stimulated with TNF-Alpha, the release of ET-1 was also observed. The
      results showed that the amount of ET-1, TNF-alpha were both increased than in the
      control group, at the same time, TNF-alpha could stimulate smooth muscle cells to
      secrete ET-1. We concluded that the release of ET-1 induced by TNF-alpha might
      play a certain role in development of airway hyperresponsiveness and airway
      remodeling.

PMID- 8762500
TI  - [The effect of furosemide and valium on band 3 protein anion transport function
      in chronic respiratory failure patients].
AB  - In order to explore the effect of drugs on band 3 protein anion transport
      function and its clinical significance, several common drugs such as furosemide,
      hydrochlorothiazide, etc, were tested. The results demonstrated that furosemide,
      hydrochlorothiazide and valium could inhibit rapidly and reversibly the anion
      transport function of band 3 protein and led to HCO-3/Cl- exchange restriction.
      The mechanism of action of the drugs was thought to be an interaction between
      drugs and the two sites of band 3 protein anion transport system. The reason that
      pulmonary encephalopathy was induced by diuretics and sedatives may be related to
      the inhibition of anion transport by the drugs and reduced CO2 elimination. It
      was necessary to be careful in using these drugs in patients with impaired lung
      function, especially the patients of cor pulmonale with type II respiratory
      failure.

PMID- 8762501
TI  - [Recurrent meningitis and spontaneous cerebrospinal fluid otorrhea].
AB  - Five children with recurrent meningitis were surgically confirmed to have
      vestibular fistula and spontaneous cerebrospinal fluid (CSF) otorrhea. The
      vestibular fistulas were successfully repaired under general anaesthesia. No
      complications were found after follow-up for 3-8 years. The etiology of CSF
      otorhinorrhea, location of fistulas, diagnosis and treatment of spontaneous
      vestibular CSF otorrhea were discussed.

PMID- 8762502
TI  - [Vibratory acoustic stimulation test in fetal hearing monitor].
AB  - In order to seek an antepartum diagnosis of hearing impairment in fetus, a
      vibratory acoustic stimulation test (VAST) was carried out with 57 women who were
      pregnant 27 weeks and an ABR test was carried out with their 57 newborn babies.
      The results showed: (1) On or after the 27th week the fetus would have the
      function of hearing. (2) The reliability of VAST was high (two positive rates
      were 87.7% and 89.5%) and the VAST was safe. (3) There was a correlation between
      fetal VAST and newborn ABR (P < 0.05). We consider that VAST is a simple, safe
      and effective measure for fetal hearing screening.

PMID- 8762503
TI  - [Endoscopic sinus surgery in children].
AB  - Thirty-seven cases (67 sides) of chronic sinusitis treated with endoscopic sinus
      surgery (ESS) at the age of 8 to 17 years were evaluated in the paper. All the
      patients after ESS were followed up for a period of 2 to 24 months. Twenty-four
      out of 37 cases were primarily healed, 7 cases had delayed healing and 2 cases
      still had persistent inflammation during the period of follow-up. Among the 37
      cases, 17 recovered completely and 20 recovered incompletely. The necessity,
      feasibility and indications of ESS in children were discussed.

PMID- 8762504
TI  - [Endoscopic sinus surgery for chronic sinusitis in children].
AB  - Anatomical features show maxillary sinus to be most commonly involved during
      childhood chronic sinusitis. Fifty-one cases who failed to respond to medications
      and irrigation were selected to undergo the middle meatal antrostomy under
      endoscopy. The majority of them had maxillary sinusitis. 10 cases had middle
      turbinate edema and polyps. 6 had ethmoiditis. After operations, signs of
      headache eliminated in 20 cases, nasal obstruction in 43 cases and yellowish
      discharge in 37 cases. The operative results were satisfactory. It is
      demonstrated that endoscopic sinus surgery is an ideal therapy for the treatment
      of childhood chronic maxillary sinusitis at present.

PMID- 8762505
TI  - [Narrowing of nasopharyngeal port for rhinolalia aperta in children].
AB  - This article describes a method of treating children with rhinolalia aperta by
      surgically narrowing the nasopharyngeal port. Eleven cases were operated on. The
      relationship between the palatopharyngeal structure and the phonology, the
      criteria for case selection and the evaluation of results were studied by the
      lateral nasopharyngeal X-ray films, videorecord of the nasopharynx, sonagram
      analysis and nasometer examination, the factors affecting treatment results has
      been analyzed clinically.

PMID- 8762506
TI  - [Measurement of Ca2+ concentration and endocochlear potential in experimental
      endolymphatic hydrops in vivo].
AB  - This study was based on observations on 14 normal guinea pigs and 17 guinea pigs
      in which the left endolymphatic duct and sac had been surgically obliterated to
      induce endolymphatic hydrops. Three groups of hydropic animals were tested 1, 2
      and 3 months after surgery. The Ca2+ concentration and endocochlear potential
      (EP) were recorded by means of double-barrelled ion selective micro-electrode in
      the third turn of the cochlea. The results indicated that a decrease in EP and an
      increase in Ca2+ in hydropic cochlea, a negative correlation was present. In the
      control ear, the values of Ca2+ and EP were 26.4 +/- 0.33 microns/L (n = 14) and
      72.78 mV (n = 14), respectively; in the hydropic ear, the value of Ca/+ was
      404.47 +/- 79.74 microns/L (n = 17), while the EP was 55.82 +/- 3.28 mV (n=17).
      According to Nerstian formula, the slope of electrochemical gradient in the
      control was 31 mV/decade (n = 14), but in the hydropic ear it increased to 72.5
      mV/decade change in Ca2+ (n = 17). The statistical analysis showed significant
      difference between the control and hydropic ears. The changes were progressive
      and became more pronounced as the duration of hydrops prolonged. The cause of
      hearing loss in the Meniere's disease and the relation between the EP and CA2+
      concentration had been discussed.

PMID- 8762507
TI  - [Collateral projections of gamma-aminobutyric acid positive neurons from the
      lateral superior nucleus to the cochlea and cochlear nucleus in guinea pigs].
AB  - Collateral projections of gamma-aminobutyric acid (GABA) neurons from the lateral
      superior olivary nucleus (LSO) to the cochlea and cochlear nuclei in the guinea
      pigs were studied by injection of two retrograde fluorescent neuronal tracers.
      For experiments, fast blue (FB) was injected into the scala tympani of one
      cochlea and diamidine yellow (DY) was injected into cochlear nuclei of the same
      side. The results showed that the FB-labelled cells and DY-labelled cells
      constituted approximately 80.8% and 12.4%, respectively; FB and DY double
      labelled cells constituted about 6%; FB and DY labelled cells with GABA
      constituted about 0.7% in the ipsilateral LSO. In the contralateral LSO, the FB
      and DY labelled cells were less than those of ipsilateral LSO and no FB-DY double
      labelled cells could be found. Our results suggest that there are collateral
      projections of GABA neurons from ipsilateral LSO to the organ of Corti and
      cochlear nuclei in the guinea pig, even though the numbers are few. The results
      also show that the efferent projections to the cochlea and cochlear nuclei
      generally come from two different auditory neuronal nuclei.

PMID- 8762508
TI  - [Study of primary organotypic culture of the chicken auditory sensory epithelia].
AB  - Organotypic explants of auditory sensory epithelia-basilar papilla (BP) were
      prepared from 8-16 days postnatal chicken and cultured in vitro for up to 7 days
      using primary culture technique. The survival status and histological features of
      the BP were studied. The results showed that morphologic integrity of hair cells
      and supporting cells was well maintained in the duration of culture and was
      comparable to those in vivo. The paradigm anchorage-bottom with bFGF/collagen as
      a substrate provided the best result, whereas the free-floating method was
      optimal for a short period of culture within 48 hours. This could be a valuable
      experimental means for further research of the auditory hair cells in vitro.

PMID- 8762509
TI  - [An animal model for cochlear microcirculatory disorders by photochemically
      initiated thrombosis].
AB  - Making an ideal animal model of cochlear microcirculatory disorders is an
      important method in studying inner ear microcirculation. After intravenous
      injection of Rose bengal (30 mg/kg), the lateral wall of the cochlea of guinea
      pigs was illuminated with green light (wavelength: 550 +/- 20 nm). The Rose
      bengal photoactivatedly produces oxygen radicals and oxygen singlets, which
      subsequently damage the endotheliocytes to cause adhesion and aggregation of
      platelets in the small vessels. After the photo-illumination, cochlea blood flow
      reduced sharply, and CAP amplitude decreased in 10 min and disappeared completely
      in about 20-40 min. With prolongation of time, stria vascularis, Corti's organ
      and spiral ganglion cells showed further disintegration due to ischemia, which
      resembled the histopathological changes of the cochlea with microcirculatory
      disorders. Therefore, this animal model may be considered an ideal one for
      studying the mechanisms of hearing loss that was caused by microcirculatory
      disorders and also for evaluating the effects of drugs on microcirculation of
      damaged cochlea.

PMID- 8762510
TI  - [The damped torsion swing test in guinea pigs].
AB  - The damped torsion swing test (DTST) was carried out for assessing the vestibular
      function in guinea pigs. Twenty guinea pigs which had normal pinna reflexes and
      normal tympanic membranes were used. In the formula, L represented the number of
      the left nystagmus, and R the right nystagmus during DTST. The symmetric rate
      [formula: see text] between left and right nystagmus was calculated. Then the
      animals were randomly divided into two groups: (1) Gentamicin group (n = 10):
      DTST was reexamined, Animals were injected with gentamicin (250 mg/kg) for three
      days. (2) Endolymphatic hydrops group (n = 10): Surgical obliteration of the
      right endolymphatic sac and duct was done, 30 days later DTST was carried out
      again. The results showed: (1) The normal value [formula: see text] of DTST in
      the 20 healthy guinea pigs is less than 8.25%. (2) Both of left and right
      nystagmus were reduced (P < 0.01) in gentamicin group. (3) The number of the
      right nystagmus was reduced in endolymphatic hydrops group (P < 0.01) and the
      symmetric rate of 6 animals was more than 8.25%. It is concluded that DTST is an
      important method of evaluating vestibular function in guinea pigs.

PMID- 8762511
TI  - [A transplantable model of human laryngeal squamous carcinoma in nude mice].
AB  - We have successfully established a human laryngeal squamous carcinoma model in
      nude mice by transplantation of surgical specimen from patients with laryngeal
      carcinoma. Histopathological study revealed squamous carcinoma. We named it
      HLC14. Light and electron microscopy showed that the morphology was similar to
      that of the original tumor. The transplanted tumor has maintained for more than
      two years through 25 passages. The tumor grew steadily and fast. The successful
      rate of transplantation was 100%. Pingyangmycine was then used to treat the
      transplantable model. The result was satisfactory.

PMID- 8762512
TI  - [The anatomy of the maxillary ostium and the middle meatus antrostomy].
AB  - Serial cadaver dissections were performed and the anatomy of the natural ostium
      of the maxillary sinus and its adjacent structures observed. The results showed
      obvious anatomic variations. In most cases, the maxillary ostium was located in
      the infundibulum, directly under the orbit. The average distance was 1.1 cm from
      the maxillary ostium to the anterior maxillary wall, showing the anatomic
      relationship of the maxillary ostium with the nasolacrimal duct. The close
      anatomic relationship between the antronasal channel and orbit was demonstrated
      by radiography. A retrospective review of 70 middle meatal antrostomies was
      conducted and discussed. The anatomy of the antronasal channel should be well
      understood by an endoscope sinus surgeon in order to perform the middle meatal
      antrostomy without injuring the orbit and nasolacrimal duct.

PMID- 8762513
TI  - [Cell culture and freeze-preservation of the human laryngeal epithelial cells].
AB  - The laryngeal epithelial cells for culture came from healthy fetuses of induced
      labor of middle and late period. Cells were cultured under 37 degrees C, 5%
      carbon dioxide and saturated humidity. The results showed that in the primary
      generation was cultured for 7 days, the aggregens could be seen by the naked eye.
      In 10-14 days, the cell layers formed and gradually covered the whole bottom of
      the flasks. The second generation grew faster than the primary one. Twenty flasks
      of the cultured cells were freeze-preserved for 14 to 28 days, of which 5 flasks
      (25%) were resuscitated successfully. By means of the cell culture, some
      characteristics of the laryngeal epithelial cells can be studied.

PMID- 8762514
TI  - [Analysis of 100 cases of precancerous laryngeal lesions].
AB  - Hundred cases of precancerous laryngeal lesions were analysed on the basis of
      clinical pathology. The results showed that there was close relationship between
      the precancerous laryngeal lesions and voice abuse and long-term heavy smoking.
      The pathology showed epithelial hyperplasis and mild to severe atypical
      hyperplasia (heterotype). Scanning electronmicroscopy revealed that the more
      severe the degree of the epithelial heterotype, the more pleomorphic the shape of
      cell morphology, margin. Twenty cases had malignant changes later, and the rate
      of malignant change was high in those with atypical hyperplasia. Some lesions
      which were taken for polyps clinically and pathologycally could also have
      malignant changes, so more attention should be paid to these lesions during
      clinical management.

PMID- 8762515
TI  - [The proliferative activity of laryngeal carcinoma and its relationship to
      histological malignancy and prognosis].
AB  - Cellular proliferation indices such as proliferating cell nuclear antigen (PCNA),
      DNA content index and mitotic figure counts (MFC) were evaluated in 70 cases of
      laryngeal squamous cell carcinoma. The results showed that there were strong
      correlations between these indices and histological grading of the carcinoma (P <
      0.01, P < 0.01, P < 0.05). Both PCNA index and MFC were related to the five-year
      survival rate (P < 0.01). The PCNA labelling index was corresponded with both DNA
      index and MFC (r = 0.61, P < 0.001; r = 0.76, P < 0.001). Our data suggest that
      cellular proliferation of laryngeal carcinoma can be reliably assessed with three
      different methods and these indices can be used as the predictor of tumor
      malignancy and prognosis.

PMID- 8762516
TI  - [Prognosis of hypopharyngeal and esophageal cancers treated with different
      surgical procedures].
AB  - Thirty-nine cases of hypopharyngeal and 21 cases of cervical esophageal
      carcinomas were resected and different organs and tissues were used for
      reconstruction. Among them, the stomach was used as substitute for the esophagus
      in 33 cases the colon in 20, the myocutaneous flap in 4 and the gastric tube in
      3. Three-year and 5-year survival rates were 61.2% and 37.9% respectively. Of the
      post-operative deaths within 5 years, 40.5% was due to local recurrence and 35.1%
      due to metastasis to cervical lymphnode. In patients who had negative lymphnode
      findings before operation, positive results were obtained in 42.1% of the
      cervical lymphnodes and in 27.2% of the tracheoesophageal groove and superior
      mediastinal lymphnodes resected. Reoperation was performed in 5 cases with local
      recurrence and 8 cases with cervical lymphnode metastasis and the resectabilities
      were 40.1% and 37.9% respectively. The authors consider that among these
      operative procedures, the colonic interposition with pharyngocolonic anastomosis
      had the following advantages: (1) excellent physiological function; (2) higher
      successful rate; (3) lower local recurrence incidence; and (4) good living
      quality.

PMID- 8762517
TI  - [Accumulation sites of kanamycin in cochlear basal membrane cells].
AB  - The dissection technique of cochlear basal membrane, the fractional technique of
      tissular homogenization, and the radiometry technique were used to study the
      toxicity of kanamycin on the hair cells. It was found that after the cochlea was
      perfused with a 0.25% perilymph solution of kanamycin, there were 3.14 fg KM in a
      nucleus, 7.61 fg KM in a mitochondria and 21.16 fg KM in a lysosome. It showed
      that after entering the cell, KM mainly accumulated with in the mitochondria.
      Simultaneously the lysosome also phagocytized a lot of kanamycin. The germicidal
      mechanism of kanamycin is to inhibit the synthesis of protein in bacteria and the
      mitochondria has the same way of protein synthesis, the mitochondria can combine
      with kanamycin specifically; the drug in lysosome may be related to its
      phagocytic function.

PMID- 8762518
TI  - [Scanning electron microscopic observation of human vestibular sensory
      epithelia].
AB  - Three-dimensional structures of human vestibular sensory epithelia were studied
      under scanning electron microscope. The saccular macula showed an "L" pattern and
      increased in thickness near the striola. The utricular macula appeared like an
      open shell. Flask and test-tube shaped hair cells were identified as type-I and
      type-II sensory cells respectively. Stereocilia were arranged in a step like
      progression; the kinocilium was near the longest stereocilium and looked more
      flexible than stereocilia. The tallest stereocilia and kinocilia faced away from
      the striola toward the periphery in the macula sacculi, and toward each other
      along the striola in the utricular maculae. Polarization directed to the utricle
      in the lateral crista, and away from the utricle in the anterior and posterior
      cristae. Otoconia varied in size and shaped like crystals with pyramidal ends.

PMID- 8762519
TI  - [Effect of streptomycin placing in the fenestra of semicircular canals on the
      function and morphology of the normal and hydropic ears in guinea pigs].
AB  - The effect of streptomycin placed in the fenestra of lateral semicircular canal
      (LSC) on the function and morphology of the normal and artificial hydropic inner
      ears in guinea pigs was studied in order to explore the method and possibility of
      treating Meniere's disease by using aminoglycosides. After placing the drug in
      the fenestra of LSC, no change in AP threshold of ECochG in normal ears but an
      increase of that in hydropic ears were found caloric induced nystagmus in both
      groups were disappeared. Under light microscope, severe damage of vestibular
      epithelium of three canal cristae and utricular macula was noted, while no insult
      of cochlear hair cells was found in normal ears. More severe damage of vestibular
      epithelium with part of them degenerated and atrophied and lesions of cochlear
      hair cells in basal turns and part of second turns occurred in hydropic ears.
      These demonstrated that the ototoxicity of streptomycin was higher in hydropic
      ears than in normal ears. In order to destroy vestibular function and preserve
      cochlear function, further study for adequate dosage of streptomycin and correct
      route of administration is needed.

PMID- 8762521
TI  - [Early diagnosis of acoustic neuroma].
AB  - The diagnostic findings in 31 patients (32 ears) with acoustic neuromas are
      reported. In patients suspicious of acoustic neuroma, case history and clinical
      examination are important. In our material of 31 patients with acoustic neuromas,
      hearing loss was presented in 94% (slow onset 87%, sudden onset 10% and
      fluctuating 3%), tinnitus in 91%, vestibular symptoms (dizziness or vertigo) in
      62%. It should be stressed that in patients with unilateral hearing loss (or
      tinnitus) or vestibular symptoms, it is necessary to exclude the presence of an
      acoustic neuroma. In addition, the trigeminal never was affected in 34%, which
      was encountered in tumours larger than 26-40 mm. There was a positive correlation
      between duration of symptoms and size of the tumour, but there was no correlation
      between hearing loss and size of the tumour. Brainstem response audiometry (ABR)
      exhibited a very high sensitivity (100%), making it a suitable single test for
      screening patients suspected to have an acoustic neuroma.

PMID- 8762520
TI  - [Study on expression and regulation of atrial natriuretic factor (ANF) gene in
      nasal mucosa].
AB  - Using 32P labelled rat ANF cDNA probe, the ANF gene transcripts in rat nasal
      mucosa and the effect of glucocorticoid and estrogen on the ANF gene transcripts
      was examined by Dot blot and Northern blot hybridization. Further more, the gene
      expression of ANF in nasal mucosa tissues of some patients with nasal diseases
      were also examined. The results showed that nasal mucosa contained ANF mRNA which
      could synthesize ANF. Both estrogen and glucocorticoid could enhance ANF gene
      expression in nasal mucosa with dose dependance. The gene expression of ANF in
      nasal polyps and inferior turbinate mucosa of patients with nasal polyps was more
      evident than that in other pathological conditions. The clinical significance of
      ANF in nasal mucosa was also discussed.

PMID- 8762522
TI  - [Retrosigmoid carding operation of facial nerve trunk].
AB  - Retrosigmoid carding operation of facial nerve trunk for treatment of intractable
      hemifacial spasm was reported in 22 patients. These cases were followed up for 1
      to 4 years. The effective rate was 87.5%. Facial nerves compressed by an arterial
      loop was found in 54.5 per cent of all cases during the operations. The operation
      was safe and no death occurred. No facial palsy was seen more than 5 months after
      the operations. The operative indication was very wide. The operation was not
      confined to those having vascular compressions. Especially the operation can
      resolve the difficult problems when no compressing vessel can be found or
      vascular decompression is difficult to do.

PMID- 8762523
TI  - [Surgical treatment of space-occupying lesions in the nasal cavity and paranasal
      sinus involving the skull base].
AB  - This paper reports 29 cases of space-occupying lesions in the nasal cavities and
      the paranasal sinuses. Of them, 12 were benign and 17 malignant. They were all
      surgically treated, 17 by lateral rhinotomy, 6 by combined cranio-nasal
      approaches, 3 by maxillectomy and evisceration of the orbit, 1 by transfrontal
      and 1 by midfacial degloving approaches, respectively. The regional chemotherapy
      was administered to a case via external carotid artery after neck dissection.
      Among these cases, 18 of the skull defects were rehabilitated. The repairing
      materials included the autologous perpendicular plate of the ethmoid bone, the
      vomer, the septal cartilage, the middle turbinate and the internal laminae of the
      frontal bone or sinus. The meningeal defects in 14 cases were repaired using
      autologous muscle, fascia, galea aponeurotica. Except for one case of
      postoperative cerebrospinal rhinorrhea due to improper surgical approach, no
      cases had postoperative complications.

PMID- 8762524
TI  - [Acoustic rhinometry: comparison of pre- and post-septoplasty].
AB  - Acoustic rhinometry (AR) is a new, objective method for evaluating the geometry
      of the nasal cavity, the cross-sectional area and the nasal cavity volume. 36
      patients with septal deformities were examined with AR. The values were compared
      with those of 21 normal controls and also the comparison was made pre-operatively
      and post-operatively in 18 patients undergoing septoplasty. The results showed
      that the minimal cross-sectional area (MCSA) was located in the anterior part of
      the nasal cavity corresponding to the area causing main nasal airway resistance
      (NAR). After septoplasty, increased MCSA with decreased NAR indicated that MCSA
      might reflect the state of nasal ventilation function properly, while the nasal
      cavity volume seemed not to be a sensitive parameter for evaluating nasal
      ventilation function. As the sensation of nasal airflow presents a different
      entity than NAR, the interpretation of the results of acoustic rhinometry and
      rhinomanometry, and the relationship with the subjective symptoms should be made
      with caution. The choice of surgical indications and the evaluation of medical
      effect should be made according to both objective examination and subjective
      symptoms.

PMID- 8762525
TI  - [Ansa cervicalis to the adductor division of the recurrent laryngeal nerve
      anastomosis for unilateral vocal cord paralysis].
AB  - The main trunk of ansa cervicalis was anastomosed to the adductor division of the
      recurrent laryngeal nerve in seven patients to reinnvervate the vocal cord for
      unilateral vocal cord paralysis. Although the reinnervated vocal cord neither
      abducted nor adducted, it presented itself in midline for precise apposition with
      the nonparalyzed cord. Normal phonatory quality was achieved after the procedure.
      Electroacoustic analysis indicated that this technique might produce normal
      phonatory function in paralyzed larynx. Laryngeal electromyography demonstrated
      that the procedure seemed to induce satisfactory reinnervation of the adductor
      musculature. Therefore, we think this technique may be recommended as an
      alternative to Teflon injection or thyroplasty in selected cases.

PMID- 8762526
TI  - [Determination of red-cell immunology in patients with laryngeal carcinoma].
AB  - In order to study the changes of the red-cell immunology, the rosette rates of
      the red cell C3b receptor (RBC-C3bRR) and red cell immune complex (RBC-ICR) were
      measured in 30 patients with laryngeal carcinoma. The results showed that: (1)
      the RBC-C3bRR and RBC-ICR were lower in patients with laryngeal carcinoma than
      those with polypus of the cord and the normal controls (P < 0.01); (2) the RBC
      C3bRR and RBC-ICR of the patients with laryngeal carcinoma did not change in
      about twenty days after operation (P > 0.05). The results suggest that the red
      cell immunological function is lowered in the patients with laryngeal carcinoma.

PMID- 8762527
TI  - [Expression of P53 protein in laryngeal carcinoma and its clinical significance].
AB  - Using the monoclonal antibody DO-7, the expressions of P53 protein in 38 cases of
      laryngeal squamous cell carcinoma (LSCC), and 29 cases of laryngeal benign
      neoplasms (LBN) were studied immunohistochemically. The results showed that: (1)
      25 of 38 (66%) LSCCs, but only 2 of 29 (7%) LBNs showed expression of mutant-type
      P53 protein. The high rate of P53 protein expression was related to the
      occurrence of laryngeal carcinoma, and is valuable in diagnosis and differential
      diagnosis of laryngeal carcinoma; (2) in some LSCCs, the mutant-type P53 protein
      was also expressed in dysplastic epithelium near the cancer tissues. These
      epithelial cells near the tumor in which P53 gene has been altered, probably are
      the source or portent of tumor recurrence; (3) the five year survival rate of
      mutant-type P53 protein negative LSCC patients was higher than that of positive
      LSCC patients. The expression of mutant-type P53 protein might be related to LSCC
      prognosis.

PMID- 8762528
TI  - [Clinical study of laryngeal and laryngopharyngeal cancers with ultra-weak
      chemiluminescence analysis].
AB  - Ultra-weak luminescence of serum in 30 normal persons and 40 patients (12
      laryngeal cancers, 18 laryngopharyngeal cancers, and 10 benign tumour patients)
      was studied using SHG-1 type photobiological photometer. The results showed that
      the intensity in malignant tumour group was higher than that of the benign group,
      which in turn was higher than that of the normal group with significant
      statistical differences (P < 0.05). The study implied that ultra-weak
      luminescence test is of value in diagnosis of laryngeal and laryngopharyngeal
      cancers.

PMID- 8762530
TI  - [Intelligence study on 1758 deaf children in China].
AB  - In order to determine the character of mental development and the influencing
      factors of childhood deafness in China the revised H-NTLA was applied to 1758
      deaf children within the age range of 3 to 17 years. Compared with 1788 normal
      hearing children, the results showed that (1) the deaf children were about 20
      points lower in IQ than those with normal hearing; (2) the average retardation
      was found to be about 6 months in 3-5 years old age, the difference became
      significant from 6 years old, the average retardation was found to be 36 months
      during 13 years old; (3) the scores were the same as those of the normal hearing
      children for block patterns, paper folding and puzzle blocks in 3-9 age groups;
      for visual attention span and spatial reasoning in 16-17 age groups. The scores
      were retarded significantly on picture association, picture analogies, memory for
      color and digits; (4) the influencing factors were found with stepwise regression
      model to be audiphone wearing, education fee and the beginning age of education.

PMID- 8762529
TI  - [Voice rehabilitation using tissue flap of trachea and esophagus].
AB  - A downward facing tissue flap from the posterior wall of trachea and the anterior
      wall of esophagus was made after total laryngectomy, then inserted into the
      esophageal cavity to form a fistula. In order to cover the fistular opening and
      also to avoid food aspiration, 2-3 mm of the valvular tip must be kept. Of 11
      cases undergoing this operation, 5 patients obtained a good vocalization, a
      comparative dysphonia occurred in 3 patients and another 3 patients got a
      esophageal voice due to shut of their fistulae. We consider this method a rather
      simple one, vocalization can recover easily without any special training, and
      also there were few complications will emerge.

PMID- 8762531
TI  - [Clinical application prospect of digital subtraction technique for periapical
      radiographs].
AB  - The composition and functions of digital subtraction system for conventional
      radiographs were introduced. Based on the experimental test for this system, it
      has been found that digital subtraction system for conventional radiographs is
      very valuable for the diagnoses of minute bone lesions in the bifurcation, root
      side and apical part of the teeth as well as in the alveolar crest. In addition,
      the reproducibility of the projection geometry, the principle of digital
      subtraction and its clinical application prospect are also discussed in the
      present paper.

PMID- 8762532
TI  - [Relationship between c-erbB-2 oncoprotein expression and prognosis in salivary
      gland malignant pleomorphic adenoma].
AB  - A monoclonal antibody AB-3 has been used immunohistochemically in a retrospective
      study of formalin-fixed paraffin embedded tissues of the salivary gland malignant
      pleomorphic adenomas (MPA). Positive staining was found in 25/60 (41.67%) of MPA.
      c-erbB-2 oncoprotein expression of the postoperative recurrent MPA group was
      higher than that of non-recurrent MPA group (P < 0.05). The postoperative 5-year
      survival rate of MPA with c-erbB-2 expression was considerably lower than that of
      without expression (P < 0.01). This observation indicates that c-erbB-2
      oncoprotein expression may be an useful prognostic indicator in MPA.

PMID- 8762533
TI  - [Adherent mechanism of the mutans of Actinomyces viscosus T14V].
AB  - Three mutans of Actionmyces viscous T14V lacking type1 (5951), type 2 (5519) and
      both types of fimbriae (147) were selected in this study. We compared the ability
      of their adsorption to the test-tube wall, the result of the cellular
      coaggregation between these mutant strains and Streptococcus sanguis 34,
      Streptococcus sanguis black bova, Streptococcus mutans ingbritte, Streptococcus
      sobrinus 6715 and analysed the chemical characterization of cell walls of the
      three mutans. We found that the specific fimbriae and cell hydrophobicities had
      great effect on the bacteria adsorption or coaggregation.

PMID- 8762534
TI  - [Clinico-pathological study on giant cell fibroma of oral mucosa].
AB  - The biopsy specimens of the Department of Oral Pathology, Dental School, UMBC,
      between 1985-1988 were reviewed in 1990 and. 124 cases of giant cell fibroma
      (GCF) of oral mucosa were found. GCF may develop at any age, but the highest
      incidence is middle adult life. GCF is slightly common in female than in male (1:
      0.85). GCF occurs frequently in gingiva, tongue and cheek and is mistaken
      commonly for irritation fibroma, neurofibroma, papilloma and pyogenic granuloma,
      because there are no specific clinic features of it. The fusiform cells, star
      cells and multinucleated giant cells in the lesion are common histologic features
      of GCF. Local removal is usually successful.

PMID- 8762535
TI  - [Palatoplasty of speech disorders and acoustical characteristics].
AB  - Some cleft palate patients suffer from disorders of articulation despite early
      surgical repair of the cleft and improvement in velopharyngeal function. Some of
      these articulation disorders involve abnormal palatolingual contact. Fifty-one
      subjects were investigated acoustically as well as management ranged from 8 years
      to 36 years with a mean age of 20 years and 1 month. Their speech disorders were
      analyzed and classified into the follows: Chinese glottal stop, pharyngeal stop,
      pharyngeal fricative, nasality, palatal articulation and lateral articulation.
      There were more than two kinds of disorder speech in one case.

PMID- 8762536
TI  - [The role of sialography in the evaluation of submandibular gland functions].

PMID- 8762537
TI  - [Clinical evaluation of force-sensitive probe in the examination of tooth
      sensitivity].
AB  - Two methods were tested for measuring the sensitivity of dentin to mechanical
      (force-sensitive probe) and cold air stimuli. Of the 212 sensitive teeth in 71
      patients, 94.8% were sensitive to probe, with a mean threshold of 22.79g; 89.6%
      were sensitive to cold air. These two methods were significantly correlated (P <
      0.001). The occlusal sites were less sensitive than the buccal sites measured by
      probe and cold air. It suggests that force-sensitive probe is a simple,
      quantitative method of measuring tooth hypersensitivity.

PMID- 8762538
TI  - [Production and characterization of specific monoclonal antibody against
      Porphyromonas endodontalis].
AB  - Porphyromonas endodontalis was known to be important microorganisms in the
      etiology of pulp and apical infection. In this paper, we generated hybridomas
      secreting monoclonal antibody against Porphyromonas endodontalis ATCC 35406. The
      specificity of the monoclonal antibody was examined by ELISA against a battery
      organisms (109 Strains). The results indicated that the monoclonal antibody did
      not react with any non-Porphy romanas endodontalis (104 Strains). So our
      monoclonal antibody is specific for Porphyromanas endodontalis and can be used in
      clinical samples for detection of pulp and apical infections.

PMID- 8762539
TI  - [Immunohistochemical study of T and B cells in dental pulp].

PMID- 8762540
TI  - [Effects of sexual hormone anticoncipiens on periodontal tissue].

PMID- 8762541
TI  - [Clinical observation of treatment of tooth hypersensitiveness with silver
      ammonia fluoride and potassium nitrate solution].

PMID- 8762542
TI  - [Swallowing pattern in skeletal Class III malocclusion].
AB  - In this research, we compared the swallowing pattern in 33 normal occlusion
      adults with that in 29 skeletal Class III malocclusion adults, using computerized
      videofluoscopy. We found that: 1) in skeletal Class III malocclusion patients,
      the tongue, the hyoid bone and the mandible were in much lower position than
      those in normal people at postural position. The gap separation between the upper
      and lower lip was much larger. So was the space between the upper and lower
      molars. During swallowing, the tongue tip moved upward and backward, and
      continually moved back along with the backward movement of the tongue dorsum.
      This was the typical tongue retraction swallowing pattern in Class III
      malocclusion. The lips kept separation during deglutition, so did the molar
      region. 2) Abnormal swallowing pattern in skeletal Angle Class III patients was
      the adaptable change with the dentoalveolar disharmony, while the long time
      abnormal swallowing could change dentoalveolar structure.

PMID- 8762543
TI  - [Pressures exerted by perioral musculature on the teeth in Angle's Class II
      malocclusion].

PMID- 8762544
TI  - [The analysis of orthodontic force for distal movement of maxillary canine].
AB  - In this study, the finite element method combining with CAD technique was used to
      establish the three-dimensional mathematical model of the right maxillary canine
      and its periodontical tissue. We imitated the different kinds of force which were
      used during the orthodontic treatment, and analyzed the ways of the teeth moving
      and the initial stress on the teeth and periodontal tissue. Results showed that
      is was best to exert couple M and force P simultaneously, especially when M/P =
      10 approximately 13 mm, the teeth could be moved fast and wholely without
      pathological destruction on the periodontical tissue. The results of this study
      provide some theoretical and experimental basis for clinical practice.

PMID- 8762545
TI  - [The effects of rat condylar endogenous prostaglandin E2 on the mandiblar growth
      and adaptation during the rat mandible functional protraction].

PMID- 8762546
TI  - [Unstable Jefferson variant atlas fractures: an unrecognized cervical injury].
AB  - Nine cases of unstable Jefferson variant atlas fractures were treated with
      nonoperative external immobilization between 1989 and 1993. All of them were
      studied by plain films and CT scans. Seven cases had three breaks of the atlas
      ring. One case had unilateral anterior arch fracture, associated transverse
      ligament tear and quadriplegia. The other case had Jefferson, Hangman, C3pedicle
      burst fractures and C3,4dislocation. All of the fractures were unstable or
      potentially unstable. Despite the abnormal open month view in all cases, the
      plain films showed minimal abnormalities, requiring CT for definite diagnosis.
      Follow-up for average of 16 months showed the 7 cases showed the fractures healed
      with good bone bunion, complete mobility and no residual pain.

PMID- 8762547
TI  - [The direct repair of the defect and grafting with single segment reduction
      fixation system in the treatment of lumbar spondylolysis and spondylolisthesis].
AB  - We designed lumbar spondylolysis and spondylolisthesis single segment reduction
      fixation system according to neural arch measured in the 46 dried specimen. The
      biomechanical tests showed that its strength is 1.6 times that of Hefti's
      technique, 2.7 times that of Salib's technique. It used contacted point lamina by
      lamina hook as fulcrum, through lever and pedicle screw to pull back olisthetic
      vertebrae. 18 patients were treated with this method. The displacemen rate was
      26.67% before operation and 3.38% after operation. The height of disc was 14.94
      mm before operation and 17.08 mm after operation. 15 patients were followed up
      for 12 months. By Henderson standard, excellent result was moted in 13 patients,
      good in 1 and fair in 1. We conclude that LSRF has good reduction and rigid
      fixation and it is a new technique for lumbar spondylolysis and
      spondylolisthesis.

PMID- 8762548
TI  - [Effects of platelet activating factor and platelet activating factor receptor
      antagonist on spinal cord blood flow after spinal cord injury].
AB  - Platelet activating factor (PAF) and PAF receptor antagonist BN52021 were
      respectively administered by intrathecal or intravenous injection in cats. We
      observed their effects on blood flow and TXB2/ 6-keto-PGF1 alpha ratio (T/K
      ratio) in injured spinal cord and its adjacent region (L2-L4)s after trauma. The
      results showed that gray matter and white matter blood flow at L2-L4 segment
      significantly decreased T/K ratio elevated evidently in PAF group as compared
      with simple spinal cord injury, while gray matter and white matter blood flow at
      L2-L4 segment significantly increased and T/K ratio markedly decreased in BN52021
      group as compared with simple spinal cord injury group. The results demonstrate
      and that PAF is an important factor leading to spinal cord blood flow reduction
      after trauma, and that PAF receptor antagonist BN52021 can evidently improve
      spinal cord blood flow and relieve secondary damage after trauma.

PMID- 8762549
TI  - [Functional rehabilitation of the urinary bladder after transection of cauda
      equina].
AB  - 12 dogs were divided into three groups of L4 root crossover anastomosis S2 root,
      sacral root free anastomosis and control. All dogs received urodynamic test
      before and after operation and before sacrifice. The results of cystometry
      demonstrated the detrusor reflex had returned 7 months after operation in two
      groups of nerve renovation. The characteristics of axonal regeneration were
      revealed by immunohisto-cytochemistry and the count of nerve fibres numbers was
      compared with that by morphometric analysis in proximal and distal end of
      anastometric stoma. The comparison displayed a significant difference between
      nerve anastomosis groups and control group. Neural tracing study with horseradish
      peroxidase (HRP) in two dogs with the operation of L4 crossover S2 showed that
      lumbar somatic motor axons had regenerated successfully into the bladder and
      replaced previous sacral parasym-pathetic. Urethral sphincter function was still
      poor and urethral pressure was not changed post-operatively, though the
      electromyograme showed some improvement. The method of lumbar root or free sacral
      root anastomosis with sacral root is practicable for restoration of bladder
      function.

PMID- 8762550
TI  - [Effect of antiserum against dynorphin A administered intrathecally on spinal
      cord injury (SCI) of rats and its significance].
AB  - The antagonistic effects of antisera against dynorphin A, beta-endorphin, and leu
      enkephailin administered intrathecally on secondary SCI were observed and
      compared after moderate SCI using principle of antigen-antibody neutralization
      reaction. The protective effect of antiserum against dynorphin A was most
      prominent on secondary SCI and the effect was more prominent when administered at
      24 hours following SCI than when administered at 0 hour four hours, one week or
      two weeks following SCI. That suggests increase of dynorphin A level in spinal
      cord tissue may play an active role in the early stage, but its harmful effect on
      secondary SCI will be more and more prominent after accumulation of excessive
      dynorphin A.

PMID- 8762551
TI  - [Changes of NGF in injured spinal cord following treatment with a single large
      dose of methylprednisolone sodium succinate].
AB  - Nerve growth factor (NGF) was detected by ABC-ELISA in rat normal spinal cord,
      spinal cord with mild contusion of 25gcm, and that with mild contusion plus a
      single intramuscular injection of large dose of methylprednisolone sodium
      succinate (MPSS) (80 mg/kg). The mean preinjury NGF level in spinal cord was 10.2
      +/- 2.8ng/g. Following injury, NGF level in spinal cord began to increase
      progressively. NGF level in spinal cord without treatment was attenuated to 30.32
      +/- 0.32, 89.51 +/- 2.14, 66.02 +/- 1.51, 50.32 +/- 1.23 and 46.23 +/- 1.42ng/g
      at 4, 7, 14, 21 and 28 days respectively, while in cord spinal with MPSS
      treatment it was 121.98 +/- 4.05, 119.56 +/- 1.45, 80.39 +/- 1.50, 68.31 +/- 0.77
      and 59.86 +/- 0.97 ng/g at 4, 7, 14, 21 and 28 days, respectively. This result
      suggests that a single large dose of MPSS enhances NGF level in injured spinal
      cord with a peak at day 4. The implication of this article is that the changes of
      NGF level in spinal cord are relevant to spinal cord self-recovery.

PMID- 8762552
TI  - [Current status of tethered cord syndrome].

PMID- 8762553
TI  - [Enhancement of gut absorptive function by early enteral feeding enriched with L
      glutamine in severe burned miniswines].
AB  - 14 miniswines (with multiple catheterization and 30% TBSA full thickness burns)
      were randomly and equally divided into N-Gln group and GLN group. Animals of GLN
      group were supplied with L-glutamine by 0.64%/kg.d and N-GLN group received equal
      amount of non-glutamine amino acids. Portal venous blood flow and gut absorptions
      of glucose, amino acids as well as fat were determined on PBD (post burn day) 1,
      4, 7 and 10. The results indicated that the gut absorption obviously decreased in
      both group on PBD1, but the absorption of glucose and amino acids were much
      higher in Gln group than that of N-Gln group (P < 0.01). The absorptions of
      glucose, fat amino acids quickly increased in Gln group from PBD4, and tended to
      reach the preburn level on PBD7 and PBD10, meanwhile N-Gln group exhibited a slow
      increase of gut absorption. The absorptions of glucose, fat and amino acids were
      obviously lower than those of preburn on PBD7 and PBD10 (P < 0.01). This result
      suggests that oral feeding of glutamine improves efficiently the gut absorptive
      function after severe burns.

PMID- 8762554
TI  - [The injury of liver and kidney of rats sustaining delayed fluid resuscitation of
      burn shock].
AB  - Delayed fluid resuscitation of burn shock may lead to many harmful effects. We
      investigated the injury of liver and kidney of rats sustaining non-fluid
      perfusion, immediate perfusion, and delayed perfusion of burn shock. The electron
      spin reonance (ESR) was used to determine the existence of oxygen free radicals
      (OFR) successfully. We tested the activity of ATP enzyme in kidney, lactate
      dehydrogenase isoenzyme 5 (LDH5), GPT and GOT. We also tested the contents of
      malonaldehyde (MDA) and ATP in liver and kidney, urea nitrogen (BUN) and
      creatinine (Cr) in blood. We found that OFR plays an important role in the injury
      of liver and kidney sustaining delayed fluid resuscitation of burn shock.
      Immediate fluid perfusion can not protect the liver and kidney perfectely. And
      some OFR scavengers should be added to the fluid resuscitation of burn shock.

PMID- 8762555
TI  - [The effect of antiseptic agents on the growth of mouse skin].
AB  - Using new born mouse skin slice culture, we studied the effects on certain
      antiseptic agents on the growth of epidermis, 0.015% approximately 1%
      chloromycin, 0.125 approximately 1% zinc sulfadiazine, 0.125% approximately 1.0%
      silver sulfadiazine markedly inhibited the expending rate of mouse skin. The
      higher the concentration of drugs, the higher is the inhibition rate. 10,000 U%
      gentamycin and 25,000U% polymyxin showed no adverse effects on skin expending
      rate. We conclude that during topical use of antiseptic agents (antibiotics or
      chemical compounds) in treatment of patients, the inhibitability of those agents
      on epidermis growth should be seriously considered.

PMID- 8762556
TI  - [Clinical analysis of anaerobic septicemia in 26 patients with extensive burn].
AB  - To understand the incidence and importance of anaerobic infection, the aerobic
      and anaerobic blood culture were carried out simultaneously in 127 patients with
      extensive burns (TBSA > 50%). Among 39 patients with positive culture, 26 had
      anaerob growth in blood culture. The total incidence rate of anaerobic septicemia
      was 20.4%. 61 strains (9 species) of anaerobes were isolated from blood
      specimens. The predominant anaerobes were Peptococcus (37.7%) and B. fragilis
      (36.1%). 20 (76.9%) were mixed infection of aerobes and anaerobes. The others
      thers suffered from combined infection of B. Fragilis and peptococcus combined
      infection. Finally, 19 patients survived and 7 died (26.9%). The sensitive tests
      showed that the effective drugs were metronidazot, chloramycin, and lincomycin.
      These data suggested that the septicemia of extensive burn patients is often
      caused by anaerobes. Therefore, anaerobe plays an important role in burn
      infection.

PMID- 8762557
TI  - [99mTc-MIBI used for diagnosis of portal hypertension: an experimental study].
AB  - The authors investigated the relationship between portal-systemic shunting and
      portal pressure in 16 CCl4-induced cirrhotic wistar rats by 99mTc-MIBI
      photography of heart and liver. Based on radio-counts taken at 30 minutes after
      99mTc-MIBI was given per rectum 8 rats or medial clonic vein 8 rats, heart radio
      counts/liver radio-counts (H/L) and portal-systemic shunting index (SI) were
      recorded. It was shown that 1. H/L and SI of the two cirrhotic groups were
      greater than those of normals (P < 0.001); 2. H/L in cirrhotic rats by rectum
      99mTc-MIBI administration was more closely related to free portal pressure (FPP,
      r = 0.83, P < 0.01) than in those by venous route (r = 0.74, P < 0.05) and its
      regressive formation FPP (kPa) = 0. 24 + 4.06 (H/L) was deduced and used to
      calculate portal pressure of cirrhotic rats. The very good relationship between
      the calculated and measured portal venous pressure was shown in a group of 12
      cirrhotic rats (r = 0.85, P < 0.01). These findings suggested that the rectum
      administration of 99mTc-MIBI may be a useful method in calculating portal
      pressure and portal-systemic shunting in portal hypertensive patients.

PMID- 8762558
TI  - [Contractile effect of erythromycin on the gallbladder].
AB  - The contractile effect of erythromycin on gallbladder has not been fully
      understood. This effect was investigated in the isolated gallbladder of golden
      hamster gallstone model and in human by ultrasonography. Erythromycicn induced
      concentration-dependent contraction of gallbladder in 28 hamsters with normal
      diet and in 13 with gallstone diet. In those two groups the maximal contractile
      effect and the half maximal effective concentration were similar (P > 0.05). In
      clinical study, the fasting volume and residual volume were significantly
      diminished in 23 volunteers and 15 with cholecystolithiasis and the ejection
      fraction and the constant emptying rate increased (P < 0.05). Erythromycin also
      modulated the hypomotility of gallbladder in gallstone patients, hence could be
      used in gallbladder hypomotility cases.

PMID- 8762559
TI  - [Experimental study of trachea reconstruction using autogenous soft tissue of
      chest wall with the stent].
AB  - The dog trachea were reconstructed after the trachea resection using the tubule
      made by autogenous intercostal compound soft tissue, including intercostal
      muscle, costal periosteum, and pleura, with pedicle of the intercostal vessels. A
      stent of fine wire was implanted inside of the reconstructed trachea as
      supporting. The postoperative result in the short period was satisfied, the
      operative complications, such as anastomotic leakage, granulation, anastomotic
      stenosis, and stent moving were not common. The tubule design, operative
      procedure, the postoperative local X-ray and the fiberscopic findings in the dogs
      were introduced. The study provides experimental evidences for clinical trachea
      reconstruction.

PMID- 8762560
TI  - [Transjugular intrahepatic portosystemic shunt: indications, prevention and
      management of complications].
AB  - Transjugular intrahepatic portosystemic shunt (TIPS) was carried out in 140 cases
      of advanced cirrhosis with portal hypertension. The success rate of TIPS was
      94.62%. The complication rate of TIPS was 16.15%, of which, 4.62% was TIPS
      procedure related including intraabdominal or intratheoracic bleeding and
      rebleeding of esophageal varices. The complication rate related to portosystemic
      shunt was 11.54% and the complications included encephalopathy and acute hepatic
      failure. The mortality of TIPS was 3.08% within one month following TIPS. 2.31%
      of patients died of hepatic failure and 0.77% died of rebleeding of varices.

PMID- 8762561
TI  - [Multi-primary colorectal carcinoma].
AB  - Twenty cases of multi-primary colorectal carcinoma were treated in the past
      twenty years. The incidence was 2.09% (20/959). Among them, seven cases had
      synchronous carcinoma (SC) and thirteen cases metachronous carcinoma (MC). After
      radical operation, the 5 year survival rate of SC was 100% (4/4), and that of MC
      83.3% (10/12).

PMID- 8762562
TI  - [Stomach cancer in pregnancy and breast feeding: report of 17 cases].
AB  - Much less frequently stomach cancer is found in pregnant woman than in general
      young man, the misdiagnosis usually takes place for the disease. 17 patients of
      this series accounted for 0.97% of all patients with stomach cancer during the
      same period (17/1752). Stomach cancer in pregnancy and breast feeding was usually
      advanced at the time of diagnosis, and the prognosis was very poor. The
      predominant pathological features of the cancer were extensive infiltration (17
      patients), diffuse growth pattern (13 patients) and undifferention of carcinoma
      (13 patients) with serious lymphonode metastasis. We suggest that the
      gastrofiberscopic and ultrasonographic examination can be used with safely at any
      time during pregnancy and facilitate early detection of stomach cancer in the
      pregnant women, especially in those who had been previously ill with precancerous
      diseases or lesions. The treatment of the disease was also discussed.

PMID- 8762563
TI  - [Gastric eosinophilic granuloma: report on 12 patients].
AB  - 12 patients with gastric eosinophilic granuloma (GEG) were diagnosed mistakenly
      to be stomach cancer before operations, including 3 patients with acute massive
      hemorrhage from upper alimentary tract and 2 patients with pyloric obstruction.
      Operations were given to all. No relapses were noted after operation.

PMID- 8762564
TI  - [Treatment of advanced malignant tumor in children: delayed primary and secondary
      operation].
AB  - 25 children with advanced malignant tumor (neuroblastoma 12, Wilm's tumor 4,
      rhabdomyoblastoma 7, embryonic carcinoma 2) were treated with delayed primary or
      secondary operation. The preoperative chemotherapy lasted for 1.03 approximately
      9.06 months (mean 3.58 months). It reduced the size of the tumor by 10.5%
      approximately 95.2% (mean 69.5%), while the resectability was 84%. The patients
      with delayed or secondary operation survived for 18.25 +/- 9.32 months, a
      significant prolongation, compared to those underwent primary operation in the
      control group (7.23 +/- 6.38 months). The indication for the delayed or secondary
      operation was discussed. From these results, it is concluded that both
      resectability and survival of the children with advanced malignant tumors have
      been improved by the combination of chemotherapy and delayed primary or secondary
      operation.

PMID- 8762566
TI  - [A study on method of measurement and analysis of anterior chamber configuration
      by computerized image processing].
AB  - A new computerized method of measurement and analysis of the anterior chamber
      configuration in the human eye is described. The image or photograph of the
      anterior chamber taken with a slitlamp microscope is inputted into a computer
      with digitized camera or digitizer. After cornea, iris and lens surfaces are
      digitized, methematical corrections are made for the distortion from the slitlamp
      microscope and the refractive effect of cornea and aqueous humor to convert an
      optic distorted image into a true image. From the corrected image of anterior
      chamber, the data and parameter of anterior chamber configuration are measured
      and calculated. The reproducibility and accuracy of the method were 1.78%
      approximately 4.66% and 0.05 mm respectively and found to be adequate for
      clinical study of human eye under physiologic or disease state.

PMID- 8762565
TI  - Clinical and pathologic studies on idiopathic uveal effusion.
AB  - In order to investigate the clinical features, pathology and treatment of
      idiopathic uveal effusion syndrome, ten eyes of seven patients with the syndrome
      had been studied. In addition to general clinical examinations, indirect
      opthalmoscopy, fundus fluorescein angiography and (FFA) ultrasonography were used
      to make definite diagnoses. The findings of these examinations indicate four key
      features of the idiopathic uveal effusion syndrome. They are: annular cilio
      choroidal detachment, shifting non-rhegmatogenous retinal detachment,
      unremarkable inflammation in the anterior segment, and normal intraocular
      pressure. The fundus change is characterized by the "leopard-spot". All patients
      were treated by sclerectomy and sclerotomy, ciliochoroidal detachments
      disappeared soon after surgery, and retinal detachments resolved later on.
      Patients' visual acuity recovered well. The histochemical and electron
      microscopic examinations of excised tissues from five eyes showed thickened
      sclera, a general increase of the scleral fibril width compared to normal
      scleral, the disruption of normal lamellar arrangement of the scleral fibers and
      the deposition of glycosaminoglycans in the interfibrillar spaces. All these
      indicate that a congenital scleral abnormality seems to be the basic
      pathophysiology of the idiopathic uveal effusion syndrome.

PMID- 8762567
TI  - [Basic study on evaluation of the fundus with monochromatic photography].
AB  - By using the monochromatic fundus photographic system we developed, fundus
      pictures of 93 normal subjects were taken under the illumination of 10 lights
      with varying wavelengths. A densitometer was used for evaluating these
      photographic results. Optimal illumination lights were selected respectively for
      photography of different layers of fundus details. The results showed that the
      degrees of contrast at the macula, optic nerve fiber layer, physiological cup of
      papilla, retinal artery and vein, optic nerve head, choroid striae are the
      highest under the illumination of light with wavelength 478nm, 478nm, 530nm,
      570nm, 628nm and 628nm respectively. The visibility of nerve fiber layer in the
      subjects over 50 years old is the highest under the illumination of light with a
      wavelength of 530nm. However, the degrees of contrast of all their fundus
      structural details, especially the macula and nerve fiber layer, are lower than
      those of subjects under 50 years old photographed with the corresponding lights
      with optimal wavelengths (P < 0.01).

PMID- 8762568
TI  - [The visual evoked potentials of non-amblyopic eyes in children with amblyopia].
AB  - We investigated the characteristics of visual evoked potentials (VEPs) of the
      eyes with normal visual acuity in 84 children of whom 20 were normal, 28 of
      anisometropic amblyopia, 8 of anisometropic amblyopia already cured, 8 pairs of
      monozygotic and 6 pairs of dizygotic twins with amblyopia. The results showed
      that although the fellow eye of an amblyopic eye or the cured amblyopic eye had
      normal visual acuity, the VEPs presented abnormal, the marked abnormality being
      the prolongation of the latency of P100 peak. No significant difference was found
      in VEPs between the eye with normal visual acuity and the eye with amblyopia in
      the monozygotic twins with the same genetic background (P > 0.05). This study
      demonstrated that possibly the clinical examinations of visual acuity and VEPs
      reflect different visual information processes, and the "normal" eyes of
      amblyopes are not normal.

PMID- 8762569
TI  - [Familial exudative vitreoretinopathy].
AB  - Familial exudative vitreoretinopathy (FEVR) is an autosomal dominant inherited
      disease. The developmental abnormality of retinal vessels is the basis of various
      lesions in FEVR. 11 affected members (21 eyes) from 5 families with FEVR were
      studied. The emphasis was placed on describing the changes of fundus and fundus
      fluorescein angiography of the disease. Argon laser photocoagulation was
      performed on 8 patients (14 eyes) and they were followed for 5 approximately 14
      months. The diagnosis, differential diagnosis, complications and treatment of
      FEVR were discussed with some materials in this paper.

PMID- 8762570
TI  - [Cataract after silicone oil tamponade and its surgical treatment].
AB  - Twelve eyes of twelve cases of cataract after complicated retinal detachment
      surgery and silicone oil tamponade were treated in this report. Successful
      extracapsular cataract extraction (ECCE) was performed on 10 of the 12 cases, no
      oil escape occurred in any of the operation and in one eye an intraocular lens
      was implanted. Intraoperatively, loss of large amount of silicone oil occurred
      and it was removed completely in ECCE in 2 cases. After the follow-up periods of
      3 approximately 30 months (mean, ten months), ten cases with the intact posterior
      capsule and silicone oil in place had a good view of the fundus, their retinae
      were attached and visual acuities were recovered above the best levels after
      retinal detachment surgery. Two cases with silicone oil removal suffered from
      retinal re-detachment. The main points of the surgery were discussed, and the
      effective method of prevention from silicone oil escape and maintenance of the
      transparency of the posterior capsule after ECCE were proposed.

PMID- 8762571
TI  - [A preliminary report on extracapsular cataract extraction with intraocular lens
      implantation in children].
AB  - Extracapsular cataract extraction (ECCE) with posterior chamber intraocular lens
      (IOL) implantation was performed on 94 eyes of children who were followed up for
      6 approximately 30 months. IOLs were inserted in all of these eyes successfully
      with anterior vitrectomy used in several cases with traumatic cataract. The
      postoperative managements were similar to those in adults, but their
      complications were severer obviously than those of adults. Uveitis was the main
      postoperative complication which was characterized by severer anterior chamber
      reaction, longer duration and easier to form posterior iris synechiae and develop
      posterior capsular opacity. The follow-up results showed that the unilateral
      recovery rate from blindness is 90.1%, and 49.4% of these patients' corrected
      visual acuities were below 0.4. Because of the controversy on IOL implantation in
      children, it is the authors opinion that it should be cautious to perform IOL
      implantation on children and such an operation is not advocated for children
      under 3 years old. Children with unilateral cataract should be managed by
      experienced doctors, and it is very important to follow up carefully, to correct
      refractive error and carry out amblyopia treatment.

PMID- 8762572
TI  - [Continuous circular capsulorhexis in extracapsular cataract extraction].
AB  - To investigate clinically the advantage, method and prevention of complication
      continuous circular capsulorhexis, a surgery consisting of continuous circular
      capsulorhexis, extracapsular cataract extraction and one-piece PMMA intraocular
      lens (IOL) implantation was performed on 52 eyes. The control was "canopener"
      capsulotomy made in 40 eyes. The residual anterior capsule and loop fixation of
      IOL were observed by dilatation of the pupil and gonioscopy 1 month after the
      operation. RESULTS: Postoperatively an anterior capsular opening of 6.5
      approximately 7.0 mm in diameter with sharp edge could be seen in 48 eyes and the
      fixation of both loops in the capsular bag was found in 44 eyes (84.6%) in
      capsulorhexis group and 21 eyes (52.5%) in "canopener" capsulotomy group. It is
      demonstrated that continuous circular capsulorhexis could maintain the integrity
      of the capsular bag and increase the chance of achieving a fixation of IOL in the
      bag.

PMID- 8762573
TI  - [The relationship between diabetic retinopathy and cataract extraction with
      intraocular lens implantation in diabetics].
AB  - 47 diabetics (71 eyes) having undergone cataract extraction with intraocular lens
      (IOL) implantation were examined and followed up. The results show that there is
      significant difference in the last post-operative visual acuities between the
      diabetic group and non-diabetic group (P < 0.01). The main cause affecting the
      post-operative visual acuities of the diabetics is diabetic proliferative
      retinopathy (P < 0.001). There is no significant difference in the post-operative
      visual acuities between diabetic group with or without simple diabetic
      retinopathy and non-diabetic group (P > 0.05). The intra- and post-operative
      complications in the diabetic and non-diabetic group were also investigated and
      there was no significant difference. IOL implantation should be guarded for
      diabetics with proliferative retinopathy especially when complicated with
      maculopathy.

PMID- 8762574
TI  - [A clinical analysis of 93 cases with corticosteroid cataract].
AB  - According to the classical diagnostic criteria, the characteristics of 93 cases
      (182 eyes) of corticosteroid cataract (CSC) were investigated to analyze the
      relationship between its lens opacity and each of the following items: the
      duration, total amount of corticosteroid used, visual acuity and glaucoma.
      Posterior capsular lens opacity can be found in a sensitive patient after four
      months of administration of corticosteroid. Juvenile and male patients are
      vulnerable to the disease. Particularly, the variation of III-grade lens opacity
      is much closely related to the duration and total amount of corticosteroid used.
      83.8% of patients were accompanied by glaucoma which may be the main cause of
      visual impairment of I and II grade lens opacity. The authors propose that CSC be
      divided into four grades according to the distribution and degree of the lens
      opacity. It should be alert that CSC might be accompanied by glaucoma.

PMID- 8762575
TI  - [Epoxide acrylate maleic resin and hydroxyapatite composite material as a bone
      graft substitute in surgical correction of orbital reconstruction].
AB  - This paper illustrates the results of surgical correction in 11 cases with
      orbital deformities such as periorbital deficiency after orbitotomy for
      retinoblastoma and orbital malposition after facial trauma. EH composite
      material, mixture of hydroxyapatite and epoxide acrylate maleic resin in constant
      proportion, was used as a good bone graft substitute in all 11 cases. This
      material was easier to be molded during surgery, safe to human body, had no toxic
      effects, no irritation and no implant-related complications. The early results
      obtained in these patients are encouraging.

PMID- 8762576
TI  - [Effect of RU486 on metabolism of glycosaminoglycans in the cultured calf
      trabecular meshwork cells].
AB  - The trabecular meshwork from newborn bovine eyes was used for cell culture and
      subculture to the third passage. Then the concentrations of RU486, a
      corticosteroid antagonist, in the medium were made to be 50, 100 and 200
      micrograms/ml and 3H-glycosamine was introduced as the radioactive precursor.
      After extraction and purification, an aliquot of glycosaminoglycans (GAGs) was
      used for cellulose acetate electrophoresis, sequential degradation by different
      enzymes and radioactivity determination by scintillation counting to determine
      the total amount of GAGs and the amounts of constituents, such as hyaluronic acid
      (HA), etc. In the control group, the total amount of GAGs was 980 DPM/micrograms
      cell prot (disintegration per minute/micrograms cell protein) and HA accounted
      for 17.8%, while in the medium of 50 micrograms/ml and 100 micrograms/ml RU486,
      HA was increased to 50.1% and 46.1%, respectively. In the medium of 200
      micrograms/ml RU486, the total amount of GAGs was decreased to 695 DPM/micrograms
      cell prot. The results were consistent with the theory of pharmacology and
      pharmacodynamics. It is possible that the corticosteroid antagonist can be used
      to reverse the pathogenesis of primary open-angle glaucoma.

PMID- 8762577
TI  - [Effect of severing trigeminal nerve on intraocular pressure and pupil in
      rabbits].
AB  - Changes of intraocular pressure (IOP) and pupil were observed through severing
      trigeminal nerve (TN), and the possible effect on TN on regulation of IOP was
      investigated in 5 rabbits. When TN was severed, the mean IOP at the same side was
      sharply and significantly elevated, being almost 2-fold of that before the
      procedure (P < 0.01). After the procedure, the mean elevated IOP decreased
      rapidly. The mean IOP at the end of the procedure was 0.28kPa higher than that
      before the procedure, and the IOP difference between pre- and post-procedure was
      not significant (P > 0.05). There was no significant difference in the comparison
      between the mean IOP after the procedure for 2 weeks and that before the
      procedure (P > 0.05). On the other hand, the mean diameter of pupils during and
      at the end of the procedure was significantly decreased (P < 0.01), when compared
      with that before the procedure, and afterward it gradually recovered. The above
      findings show that the rapid and significant reactions of IOP and pupil during
      the procedure are possibly affected by the actions of some neuropeptides in the
      TN5 suggesting that TN, participate in the regulation of IOP.

PMID- 8762578
TI  - [Lens epithelial proliferation induced by macrophages after intraocular lens
      implantation in rabbits].
AB  - To approach the effect of intraocular lens implantation on the mechanism of
      posterior capsular opacification, the pathological changes of posterior lens
      capsule after intraocular lens implantation in rabbits were observed by
      transmission electron microscopy. The results were as follows: In the control
      group, 1 week after the operation and the injection of the medium of the
      macrophage suspension, the lens posterior capsule was covered by a layer of lens
      epithelium and until post-operative 6 months, the lens epithelium remained
      normal. In the experimental group, 1 week after the operation and the injection
      of the macrophage suspension into the anterior chamber, microfilaments appeared
      in the cytoplasm of lens epithelial cells, after 2 weeks, the lens epithelial
      cells produced collagen fibrils in the extracellular matrix and until
      postoperative 3 months, 2-3 layers of the lens epithelium proliferated in front
      of the posterior capsule and a large amount of collagenous fibers were formed
      around the cells. It is suggested that the macrophage promote the lens epithelial
      proliferation and the posterior capsular opacification.

PMID- 8762579
TI  - Elastase inhibitory capacity of purified canine alpha-1-antitrypsin.
AB  - In a previous study, isoelectrofocusing of serum from liver-diseased and healthy
      dogs revealed three different types of the acute phase protein, alpha-1
      antitrypsin: Pi (protease inhibitor) F, Pi I and Pi S. Moreover, accumulated
      alpha-1-antitrypsin was found immunohistochemically in liver sections from dogs
      with chronic liver disease, predominantly in association with Pi I in serum. The
      present study was made to further the relationship between alpha-1-antitrypsin
      and the pathogenesis of chronic liver disease in dogs. Aliquots of samples of
      purified canine Pi F, Pi I and Pi S were examined for elastase inhibitory
      capacity, the main function of alpha-l-antitrypsin, and for polymerization
      tendency, a possible cause of accumulation of alpha-1-antitrypsin in the liver.
      These parameters were studied after incubation of the proteins at different
      temperatures (4, 37 and 42 degrees C) and pH values (6.8, 7.8 and 8.5) and for
      different periods (< or = 24 h and 5 days). In contrast to findings with Pi Z,
      the human alpha-1-antitrypsin variant associated with liver disease, polymers of
      canine Pi F, Pi I or Pi S could not be detected under any of the conditions
      tested. However, Pi I was sensitive to pH, as was demonstrated by reduced
      elastase inhibitory capacity after incubation at pH 6.8 for < or = 24 h or 5
      days, or at pH 8.5 for 5 days. However, after incubation at pH 7.8 for < or = 24
      h or 5 days at 4, 37 or 42 degrees C, Pi I was completely stable. Pi F retained
      its elastase inhibitory capacity, even after prolonged incubation, at all pH
      values and temperatures tested. Due to low yield, Pi S was tested only after
      incubation for < or = 24 h at pH 6.8 and at 4 degrees C; under these conditions
      its elastase inhibitory capacity was equal to that of Pi F. Taken together, these
      findings indicate molecular and functional differences between Pi I and Pi F and
      further support a role for alpha-1-antitrypsin in the pathogenesis of canine
      liver disease.

PMID- 8762580
TI  - Pathogenesis of Chlamydia psittaci infection in sheep: detection of the organism
      in a serial study of the lymph node.
AB  - Sixteen sheep were inoculated subcutaneously over the left prefemoral lymph node
      with an abortifacient strain of Chlamydia psittaci. Groups of four animals were
      killed after 3, 6, 12 and 18 days. Four of eight sheep which received a control
      inoculum were killed on day 6 and four on day 18. The left and right prefemoral
      lymph nodes were removed and weighed and portions taken from each for examination
      by the polymerase chain reaction (PCR), by culture, and by histopathological and
      immunohistochemical methods. The left prefemoral lymph nodes enlarged after the
      injection of C. psittaci, with the group mean weight on day 6 being the greatest
      and that on day 18 being normal. Examination by "nested" PCR showed samples from
      these nodes to be positive, except for one animal killed on day 3 and one on day
      12. Live organisms, however, were not cultured from any of the samples collected.
      C. psittaci antigen was detected immunohistochemically in three of four nodes on
      day 3, in each of four on day 6, and in two of four on both days 12 and 18. Nodes
      from the contralateral side remained normal, as did those from unchallenged
      control sheep, and no antigen or DNA was detected in them.

PMID- 8762582
TI  - Increased metabolism of collagen VI in canine osteoarthritis.
AB  - The integrity of joint function depends on both the extracellular matrix and the
      chondrocytes of articular cartilage. It has been suggested that there is a
      reciprocal relationship between these two components, which is altered in
      osteoarthritis. The immunohistochemical distribution of type VI collagen in
      normal and osteoarthritic canine cartilage was investigated by immunofluorescence
      and immunoelectron microscopy. Immunogold labelling showed that in normal
      cartilage type VI collagen was concentrated in the capsule adjacent to the
      chondrocyte complex. However, in osteoarthritic cartilage, type VI collagen was
      also observed throughout the cartilage matrix and was greatly increased in the
      territorial matrix and pericellular capsule surrounding the chondrocytes.
      Naturally occurring canine osteoarthritis provides a useful model for the study
      of the human disease, particularly the early stages. The changes in type VI
      collagen observed in osteoarthritis suggest an attempt at cartilage repair,
      resulting in the reorganization of the matrix.

PMID- 8762581
TI  - A comparison of equid herpesvirus-1 (EHV-1) vascular lesions in the early versus
      late pregnant equine uterus.
AB  - Four Welsh Mountain pony mares at 3 months of gestation and one mare at 5 months
      were inoculated intranasally with equid herpesvirus-1 (EHV-1: Ab4 isolate) at
      doses of 10(5) to 10(6.6) TCID50. All five mares became infected, but no cases of
      paresis or abortion occurred. On days 8, 9, 11, 12 (3-month-pregnant mares) and
      13 (5-month-pregnant mare) after infection, a detailed examination of the
      pregnant uterus was made. Small numbers of vascular lesions with EHV-1 antigen
      expression in endothelial cells were present in the uteri of the early
      gestational mares; thrombi were rare and foci of thromboischaemic damage were not
      seen. Six pony mares previously inoculated with EHV-1 Ab4 at 9 months of
      gestation had a significantly greater degree of vascular abnormality than that
      found in the four mares infected at 3 months of gestation, but the degree of EHV
      1 antigen expression and thrombosis in the uterus was similar to that found in
      the single mare infected when 5 months pregnant.

PMID- 8762583
TI  - Viral antigen and B and T lymphocytes in lymphoid tissues of gnotobiotic piglets
      infected with hog cholera virus.
AB  - Four 4-day-old gnotobiotic piglets infected intranasally with the Kanagawa/74
      strain of hog cholera virus (HCV) did not develop severe illness over a period of
      3 weeks. Large amounts of HCV were isolated from the lymphoid tissues and serum
      at necropsy. After the acute phase, hyperplasia of histiocytes and
      plasmacytopoiesis were observed in two pigs (killed 14 and 21 days after
      inoculation). The number of CD4+ and CD8+ T lymphocytes increased significantly
      and their location was consistent with the site of HCV replication. The results
      suggest that a CD8+ T-lymphocyte reaction is associated with persistent HCV
      infection.

PMID- 8762585
TI  - Immunoglobulins of camel (Camelus dromedarius) colostrum.
AB  - Immunoglobulins G, M and A were identified in dromedary camel colostra by acid
      precipitation, gel filtration and fast-protein liquid chromatography (ion
      exchange). Heavy and light chains were identified by polyacrylamide gel
      electrophoresis and Western blotting. IgG subclasses (IgG1, IgG2 and IgG3) were
      isolated by DEAE ion-exchange chromatography and shown to have different
      electrophoretic mobilities. Cross-reactivity of camel IgA with IgA of other
      species was determined by enzyme-linked immunosorbent assay (ELISA). Most of the
      immunoglobulin content was IgG, but a molecule identifiable as IgA was detected
      and purified. It would appear that in the camel, as in cattle, IgG is the major
      secretory immunoglobulin of colostrum.

PMID- 8762584
TI  - Immunohistochemical demonstration of S-phase cells by anti-bromodeoxyuridine
      monoclonal antibody in cattle tissues.
AB  - Bromodeoxyuridine (BrdU), a non-radioactive thymidine analogue, was administered
      to 15 cattle at a dosage of 1-10 mg/kg intravenously or intraperitoneally to
      demonstrate S-phase cells in the tissues. The organs and tissues were fixed in
      10% neutral buffered formalin or in 70% ethanol, sectioned, denatured with
      hydrochloric acid, and treated with monoclonal antibody against BrdU.
      Immunohistochemical methods were used to "visualize" BrdU-labelled nuclei. BrdU
      positive cells were satisfactorily demonstrated in both formalin- and ethanol
      fixed tissues of animals given doses of 2 mg/kg or over, by either route of
      administration. Large numbers of BrdU-positive cells indicative of active cell
      production were found in the basal region of the stratified squamous epithelium,
      the neck between gastric pits and gastric glands in the abomasum, and the crypts
      of Lieberkuhn of the small and large intestines. Moderate numbers of positive
      cells were observed amongst inflammatory cells in cases of nephritis and in
      granulation tissue. Numerous positive cells were detected in leukaemia cells. The
      study showed that BrdU can be used to measure proliferative S-phase cells in
      cattle, as in human beings, mice and rats.

PMID- 8762586
TI  - Ultrastructure of hepatocytes in copper-deficient Sika deer (Cervus nippon
      Temminck).
AB  - The livers of 13 Sika deer (Cervus nippon Temminck) aged 4 to 9 years and
      suffering from copper deficiency (enzootic ataxia) were examined histologically,
      histochemically and by electron microscopy. In addition, the serum and liver
      copper concentrations, measured in three animals, were found to be low.
      Histologically, the hepatocytes exhibited cloudy swelling, and numerous
      haemosiderin deposits were seen in the hepatocytes and Kupffer cells. Staining
      with p-dimethyl amino-benzylidene-rhodamine revealed distinctly fewer copper
      granules than normal. Histochemically, 3,3'-diaminobenzidine-H2O2 staining
      revealed increased numbers of catalase-positive granules around nuclei. Electron
      microscopically, "giant" and bizarre-shaped mitochondria, irregular depression of
      the mitochondrial membrane, and fusion of cristae were noted. Disorders of copper
      containing enzymes, including cytochrome oxidase, caeruloplasmin and monoamine
      oxidase, may have been responsible for the mitochondrial abnormalities.

PMID- 8762587
TI  - Histopathological changes in the pituitary glands of female hamsters infected
      with the 139H strain of scrapie.
AB  - Previous studies in hamsters showed that the 139H strain of scrapie injected
      intracerebrally caused a generalized endocrinopathy and marked hypoglycaemia and
      hyperinsulinaemia. The low scrapie infectivity levels in the pancreas suggested
      that the changes noted in that organ were of neuroendocrine origin. In the
      current study, female weanling Syrian hamsters were inoculated intracerebrally
      with scrapie strain 139H or 263K, or with homogenate of normal hamster brain.
      Coronal sections of the pituitary gland were stained with haematoxylin and eosin,
      Gomori's one-step trichrome, Congo red, thioflavin-S, and antibodies specific for
      several pituitary hormones. Sections were examined by light microscopy. The
      hamsters inoculated with scrapie strain 139H showed extensive pituitary
      vacuolization. Most vacuoles were located in the ventral or ventrolateral parts
      of the pars distalis. The pituitary glands of 139H-infected hamsters also showed
      cellular changes, namely, hypertrophy, atrophy and cytoplasmic vesicles. Nuclear
      changes such as swelling, vesicle formation, chromatin increase, pyknosis,
      karyorrhexis and karyolysis also occurred. The cellular and nuclear changes were
      most pronounced in the regions with vacuolation. Hamsters infected with the 263K
      strain did not show these changes. Immunocytochemical examination suggested that
      parenchymal cell types which produce different hormones were affected in areas of
      vacuolation. The changes produced by 139H were not seen in hamsters infected with
      strain 263K. This study provides the first evidence of cytopathological changes
      in the pituitary glands of scrapie-infected animals and suggests a relationship
      between the pituitary changes and the pathological findings in the pancreas and
      other endocrine organs of 139H-infected hamsters.

PMID- 8762588
TI  - Calcifying epithelial odontogenic tumours in small domesticated carnivores:
      histological, immunohistochemical and electron microscopical studies.
AB  - Histological, immunohistochemical and electron microscopical studies revealed one
      feline and four canine calcifying epithelial odontogenic tumours in 115 oral
      tumours over a 10-year period. The tumours consisted of islands and sheets of
      odontogenic epithelium of varying size within a stroma of fibrous connective
      tissues. The tumour cells were pleomorphic with variable amounts of eosinophilic
      cytoplasm and large hyperchromatic, polymorphic nuclei with prominent nucleoli.
      Clusters of keratinized tumour cells ("shadow cells") were frequently seen within
      the islands and sheets. The multiple spherules of homogeneous eosinophilic
      material stained positively with Congo red and Dylon stains and produced an apple
      green birefringence under polarization microscopy, indicative of amyloid.
      Mineralized foci were scattered throughout the tumour masses and in the
      homogeneous spherules. Immunohistochemically, the tumour cells reacted with anti
      human keratin antibody, but not with anti-human vimentin or anti-chicken desmin
      antibodies. The homogeneous spherules did not react with anti-human keratin, anti
      human vimentin, anti-chicken desmin, anti-amyloid A, anti-laminin or anti-human
      collagen (type I, III, IV) antibodies. Ultrastructurally, the cytoplasm of tumour
      cells was abundant and contained a large number of electron-dense bundles of
      tonofilaments. The homogeneous spherules consisted of fine filaments measuring
      about 10-12 nm in diameter.

PMID- 8762589
TI  - Detection of porcine reproductive and respiratory syndrome virus and Mycoplasma
      hyorhinis antigens in pulmonary lesions of pigs suffering from respiratory
      distress.
AB  - Eleven field cases of a disease characterized by severe dyspnoea or abdominal
      breathing were examined post mortem. The affected pigs had antibody against
      porcine reproductive and respiratory syndrome virus (PRRSV). The predominant lung
      lesions were severe proliferative and interstitial pneumonia, and slight
      suppurative bronchopneumonia. The lesions were closely associated with the sites
      at which PRRSV and Mycoplasma hyorhinis antigens were detected. Four of five pigs
      inoculated with PRRSV developed slight pneumonitis. The fifth animal, which died
      of severe pneumonitis, yielded a heavy culture of M. hyorhinis. These findings
      demonstrate that dual infection with M. hyorhinis and PRRSV caused severe
      pulmonary lesions.

PMID- 8762590
TI  - Inherited muscular disorder in mutant Japanese quail (Coturnix coturnix
      japonica): an ultrastructural study.
AB  - Ultrastructural study of muscles taken from a mutant (LWC) strain of Japanese
      quail with myotonia showed type 2 fibre atrophy, ring fibre formation,
      sarcoplasmic masses, and "moth-eaten" fibres. In these abnormal fibres, the most
      characteristic feature was the loss of interconnection among the myofibrils,
      mitochondria, and T tubules. Apparently normal muscle fibres often showed mild
      changes, such as proliferation of T tubules and enlarged sarcoplasmic areas with
      increased glycogen granules and ribosomes at the periphery of the fibres. The
      study suggested that one possible cause of these ultrastructural changes was a
      defect in cytoskeleton of muscle cells, especially in intermediate filaments.

PMID- 8762591
TI  - Evaluation of an immunoradiometric assay for thyrotropin in serum and plasma
      samples of dogs with primary hypothyroidism.
AB  - A commercially available immunoradiometric assay was used to measure the
      thyrotropin (TSH; thyroid-stimulating hormone) concentration in the serum and
      plasma of 23 dogs. The basal concentration in five dogs with histologically
      confirmed primary hypothyroidism (median 0.18 microg/l, range 0.16-0.72 microg/l)
      was slightly, but not significantly, higher than that in 13 clinically healthy
      dogs (median 0.09 microg/l, range 0.06-0.34 microg/l). The TSH values in 11
      euthyroid dogs with various dermatological diseases (median 0.09 microg/l, range
      0.05-0.53 microg/l) were significantly lower than in the hypothyroid dogs, but
      there was considerable overlap. The assay alone was therefore not capable of
      giving a firm diagnosis.

PMID- 8762592
TI  - Innominate artery compression of the trachea in infants.
AB  - Compression of the airway by the innominate artery has been a controversial cause
      of stridor and apnea in infants. Magnetic resonance imaging has been applied to
      document the possible association of segmental tracheomalacia. Forty infants with
      symptoms of stridor were studied, 7 of 40 infants aged 3-21 months (mean 10
      months) had innominate artery compression on the trachea. Five infants were
      treated conservatively and two infants underwent surgery. Flattening of the
      trachea was longer than the mass compression point by the innominate artery.
      Therefore, intrinsic abnormality of the trachea is the basis of the respiratory
      symptom.

PMID- 8762593
TI  - Nasal foreign bodies in children.
AB  - This study investigates the pattern of pediatric nasal foreign body impaction and
      its management in a metropolitan area. Data was obtained from 147 children
      presenting to the Accident and Emergency Department over a 4-year period. The
      majority of foreign bodies were toys and household products. Complications which
      occurred, such as ingestion of the foreign body or epistaxis were usually related
      to attempts at removal. Fourteen cases of local complications resulted from
      button battery impaction. Most of these patients can successfully be managed
      without complication if correct procedures are adopted.

PMID- 8762594
TI  - Parapharyngeal abscess in children: the role of CT for diagnosis and treatment.
AB  - Parapharyngeal abscess (PPA) in children is an uncommon deep neck space
      infection. Computerized tomography (CT) is an important diagnostic aid. However,
      CT scan is not specific in differentiating an abscess from cellulitis or
      inflammatory edema. A retrospective review of eight children with a CT diagnosis
      of PPA was undertaken. In three patients an abscess was surgically confirmed. In
      two patients surgical exploration did not reveal an abscess and in three the
      infection resolved with intravenous antibiotic therapy only. Although CT is a
      useful diagnostic tool for PPA, surgical intervention should be based mainly on
      the clinical status of the patient and the non-responsiveness to i.v. antibiotic
      therapy.

PMID- 8762595
TI  - Sensorineural hearing loss in children with thalassemia major in Northern Greece.
AB  - Eighty eight (88) beta-thalassemic patients undergoing regular transfusion-
      chelation therapy with desferrioxamine (DFO) were studied for ENT problems from
      1988 to 1993, as DFO has been implicated for auditory neurotoxicity. The mean age
      of the patients was 9.66 +/- 3.1 years, their pre-transfusion haemoglobin level
      was 9 +/- 2 g/dl, serum ferritin level was 2065 +/- 898 ng/ml and the daily DFO
      dose was 50.7 +/- 9.5 mg/kg for 5 days/week. The ENT study included, ENT
      examination, pure tone audiometry, speech audiometry, tympanometry, tone decay
      test and ABR. During this 6-year study 24/88 (27%) patients developed bilateral
      or ipsilateral sensorineural hearing loss in high tone frequencies, sometimes
      exceeding 80 dB, which was attributed to DFO toxicity. Therefore, a reduction or
      temporary withdrawal of DFO followed. After this intervention 12/24 patients
      recovered almost completely, 7/24 remained stable and 5/24 presented aggravation
      of their hearing loss. This study confirms the DFO induced auditory neurotoxicity
      and the necessity of periodical audiology control of beta-thalassemic patients
      for prompt diagnosis and management of this complication.

PMID- 8762596
TI  - Otitis media with effusion and S-carboxymethylcysteine and/or its lysine salt: a
      critical overview.
AB  - An overview of the placebo-comparative articles retrieved by a literature search
      on Medline - Embase - Biosis data banks from 1972 to 1993 was performed to
      evaluate the therapeutic relevance of the medical treatment with S
      carboxymethylcysteine (SCMC) and its monohydrate lysine salt (SCMC-LYS) in
      patients with otitis media with effusion (OME). Ten original published studies
      were reviewed by an independent physician who assessed their quality by standard
      nine-items methodology. A meta-analytical approach was used to compare outcomes
      across all qualifying studies. Because of the heterogeneity of clinical
      endpoints, a new outcome measure was defined, i.e. overall clinical improvement,
      which consisted of the number of patients with complete resolution of clinical
      signs and symptoms and no need for surgical intervention. The objective
      evaluation criteria of normalisation of tympanogram was an additional end-point.
      Potential confounding variables such as eligibility criteria, treatment protocol
      and study design of the six methodologically complying studies were statistically
      homogeneous. No association was found between treatment effect-size and
      publication date or patients' age. Outpatients with disease duration of < 6
      months, not previously treated, with bilateral ear involvement were included in
      the studies; half of them presented hyperplasia or hypertrophy of the pharyngeal
      or the adenoid tissue. Out of 483 patients, 430 (89%) terminated studies and were
      evaluable. Results from this meta-analysis indicate that patients with OME
      receiving oral SCMC/-lys benefit from the medical treatment to the extent of
      avoiding surgical intervention approximately 2.31 times more often than similar
      patients receiving placebo (ratio of active drug to placebo-effect on overall
      clinical improvement: 2.31; C.I. 1.28-4.20, P < 0.01) and attain reversion to
      normal of the tympanogram at an extent close to statistical significance (odds
      ratio: 2.25, C.I. 0.97-5.22, P = 0.058). In conclusion, the use of this new
      methodology for the evaluation of the mucoactive drug effect in OME has shed
      light into methodological pitfalls of clinical trials to date and underlines the
      need for agreed outcome measures, which may modify medical policy, which
      addresses more and more often to symptomatic treatment.

PMID- 8762597
TI  - Expression of antigens associated with the individual stages of the inflammatory
      response in child and adult as a possible distinctive method for recurrent and
      chronic tonsillitis.
AB  - Monoclonal antibodies (MoAbs) specific for the antigens associated with each
      stage of an inflammatory response were assayed with tonsillar mononuclear cells
      (TMNG). MoAbs BMA 27 E 10 and BMA 4 D 10 were used as markers for the early
      stages, BMA RM 3/1 for the intermediate stage, BMA 25 F 9 for the late stage, and
      BMA G 16/1 for the chronic stage. TMNC were obtained from patients operated for
      (1) recurrent tonsillitis with hypertrophy caused by common flora (children); (2)
      an indication for surgery for chronic tonsillitis in adults; (3) patients who
      were 'warm' tonsillectomized for a second peri-tonsillar phlegmon. Our results
      are presented and discussed in the light of their possible clinical significance.
      Our findings indicate that clinical chronic tonsillitis in the adult really is
      such. In the adults studied there was a high expression of antigens which is
      associated with the chronic stages, while the low expression of antigens is
      associated with the intermediate stage and an even lower antigen expression
      indicates the acute stage. In children what is considered to be chronic
      tonsillitis may perhaps be more correctly regarded as an expression of recurrent
      inflammation.

PMID- 8762598
TI  - Acquired laryngeal stenosis in infants and children treated by laryngofissure and
      stenting.
AB  - Thirty young patients with acquired laryngeal stenosis were treated by means of a
      laryngofissure and stenting. The age distribution suggested two subgroups:
      infants aged 0-2 years (n = 24), and children aged 6-16 years (n = 6). The causes
      of the stenosis and the treatment results were different in these subgroups.
      Treatment resulted in successful decannulation in 22 of 24 infants, and in 5 of 6
      children. Treatment included a re-operation in two patients. In 1 patient the
      therapy failed, and 2 patients died after fatal complications. Decannulation
      rate, duration of the tracheotomy, and the number of re-operations compare
      favorably to the results of other centers. The longer duration of stenting, and
      the high mortality rate may be considered disadvantages.

PMID- 8762599
TI  - Pediatric cervical esophageal perforation secondary to abusive blunt thoracic
      trauma.
AB  - Cervical esophageal perforation secondary to blunt trauma is extremely rare. A
      case of an 8-week-old infant that sustained a cervical esophageal perforation
      from abusive acceleration/deceleration blunt trauma is presented. Early diagnosis
      and appropriate intervention of an already insidious injury can be further
      delayed by the lack of concise temporal events and falsification of data from the
      abusive caretaker(s). In-depth history taking, documentation and notification of
      authorities lays the critical medicolegal groundwork for this unfortunately
      increasing problem in our society. Diagnosis and management are discussed. The
      pediatrician, emergency department, nursing staff and otolaryngologist should
      have strong suspicions of abuse when esophageal perforation is identified in an
      infant.

PMID- 8762600
TI  - Neonatal septoplasty: case report and review of the literature.
AB  - Treatment of nasal septal deformity in childhood has received growing acceptance
      in recent years. Traditionally, concern about the role of the septum in the
      overall growth of the midface has led otolaryngologists to take a very cautious
      approach to correction of septal deformities in children. However, a great deal
      of evidence now suggests that severe traumatic septal deviation can and should be
      corrected early in childhood to prevent future nasal and systemic complications.
      Closed manipulation of the septum in the first 1-2 days of an infant's life has
      been performed by many otolaryngologists with good results. The use of this
      technique, however, is usually limited to those subluxations of anterior
      cartilage which are diagnosed immediately or very shortly after birth. We present
      a case of severe traumatic nasal deformity presenting with obstructive asleep and
      awake apnea and cyanosis at the age of 8 days. The child underwent limited
      septoplasty using endoscopic techniques at age 14 days with resolution of both
      the apneic and cyanotic episodes immediately post-operatively. This unusual
      presentation and the literature surrounding infant nasal/septal surgery are
      discussed.

PMID- 8762601
TI  - Badgers, bovine tuberculosis and the age of reason.

PMID- 8762602
TI  - Poultry in transit--a cause for concern?

PMID- 8762603
TI  - Antigens with application toward immune control of blood-feeding parasitic
      nematodes.
AB  - This review considers progress toward immune control of nematode parasites that
      feed on mammalian host blood. Approaches to identify relevant parasite antigens
      include use of irradiated larvae, somatic antigens, metabolites, enzymes and gut
      antigens. Because significant immune protection has more recently been achieved
      using gut antigens of the blood-feeding parasite Haemonchus contortus, these
      antigens are considered in greater detail. Issues discussed are implications of
      gut antigens in immune control, potential mechanisms involved in this immunity,
      biochemical characteristics of gut antigens and potential application of gut
      antigens to immune control of other blood-feeding nematodes.

PMID- 8762604
TI  - Malassezia pachydermatis with special reference to canine skin disease.
AB  - A review of the diseases caused by Malassezia pachydermatis has led to the
      conclusion that the yeast is an opportunistic pathogen that depends on
      predisposing host factors and different immune suppressive mechanisms for
      clinical manifestation. Until recently, the role of M. pachydermatis in
      seborrhoeic dermatitis and otitis externa in dogs has been largely unrecognized.
      The clinical manifestation, aetiology, diagnosis and treatment of disease
      conditions in dogs caused by M. pachydermatis are reviewed. Human Malassezia
      furfur infections are briefly described.

PMID- 8762605
TI  - The pathogenesis of chronic obstructive pulmonary disease of horses.
AB  - Present evidence suggests that chronic obstructive pulmonary disease (COPD) of
      horses is a delayed hypersensitivity response to inhaled antigens, particularly
      the thermophilic moulds and actinomycetes that grow in damp hay. Within several
      hours of exposing COPD-susceptible horses to such hay, neutrophils invade the
      lung and accumulate in the lumens of airways, particularly bronchioles. The
      inflammatory response is accompanied by increased levels of histamine in
      bronchoalveolar lavage fluid, increased plasma levels of the inflammatory
      mediators thromboxane and 15-hydroxyeicosatetraenoic acid (15-HETE), and a
      decrease in the production of prostaglandin (PG) E2 by the airway mucosa. During
      acute exacerbations of COPD, airways exhibit nonspecific hyperresponsiveness and
      become obstructed as a result of bronchospasm and the accumulation of mucus and
      exudates. Bronchospasm is due largely to activation of smooth muscle muscarinic
      receptors by acetylcholine (ACh). Because the in vitro response of smooth muscle
      to ACh is unaltered, the increase in airway smooth muscle tone is probably a
      result of activation of airway reflexes by inflammatory mediators and decreases
      in inhibitory mechanisms such as the intrapulmonary nonadrenergic noncholinergic
      nervous system and the production of PGE2 in affected horses. The diffuse airway
      obstruction leads to uneven distribution of ventilation, ventilation/perfusion
      mismatching, and hypoxaemia. As a result of the increased respiratory drive
      caused by hypoxaemia and the presence of airway obstruction, horses adopt a
      characteristic breathing strategy in which very high peak flows at the start of
      exhalation rapidly diminish as exhalation proceeds.

PMID- 8762606
TI  - A survey to investigate potential dehydration in slaughtered broiler chickens.
AB  - A survey of 800 broilers arriving at two commercial slaughterhouses with a
      combined annual throughput of 40 million birds was carried out. Each plant was
      visited on four occasions throughout summer and winter and blood samples were
      collected from 100 broilers at exsanguination throughout the day of each visit.
      In all, the survey covered 16 lorry loads of broilers delivered to one plant and
      20 loads delivered to the other. The blood collected was analysed for packed cell
      volume (PCV), plasma creatine kinase, total protein, sodium, glucose, osmolality
      and corticosterone. Based on the measures of PCV, plasma total protein, sodium
      and osmolality there was no evidence of dehydration amongst the lorry loads of
      birds delivered to the plants. There were differences between the two plants in
      the levels of all of the blood variables that were measured, except for those of
      plasma corticosterone.

PMID- 8762607
TI  - Influence of exogenous and endogenous acth on adrenal cortex activity in calves
      during the early postnatal period.
AB  - A study was carried out on 66 black-and-white calves during the period from birth
      (day 0) to day 21 of life. Blood plasma adrenocorticotrophic hormone (ACTH) and
      cortisol concentrations were determined by radio-immunoassay and the influence of
      exogenous and endogenous ACTH on adrenocortical activity assessed. An ACTH
      induced adrenal cortex response was observed as early as day 0, whereas a
      definite relationship between ACTH and cortisol concentrations emerged in the
      second week of life. It is concluded that the pituitary-adrenal axis is blocked
      during the first week of life and this effect seems to be related to high
      cortisol concentrations and an elevated reactivity threshold of the adrenal ACTH
      receptors.

PMID- 8762608
TI  - Claw conformation of dairy heifers in two management systems.
AB  - A computerized conformation determination system was used to evaluate objectively
      claw conformation of dairy heifers in two management systems, i.e., housed
      indoors on concrete slats or out of doors in a dry lot. Examinations were made at
      4-week intervals from 12-13 months of age until calving at 24-26 months. Overall,
      the angle of the dorsal border did not differ between front and hind claws.
      Length of the dorsal border, heel height, and toe:heel ratio were greater for
      front claws (P < 0.001). Hind claws were longer than front claws (P < 0.001), but
      front claws were wider (P < 0.001). On both front and hind limbs, lateral claws
      were wider than medial claws (P < 0.001). Angles of the dorsal border decreased,
      but lengths of the dorsal border and heel heights increased over time (P < 0.05).
      Significant differences in claw conformation were found between the two
      management groups. Heifers maintained out of doors had longer toes and wider
      lateral claws than heifers housed indoors (P < 0.05). At time of entry into the
      respective management group, no significant differences in claw traits were found
      between the two groups. At calving, however, out-door-housed heifers had hind
      claws with smaller dorsal angles and longer dorsal borders (P < 0.05).

PMID- 8762609
TI  - Ultrastructural alterations in pigs with naturally occurring hypertrophic
      cardiomyopathy.
AB  - Naturally occurring hypertrophic cardiomyopathy (HCM) in pigs in generally
      characterized by unexplained cardiac hypertrophy with abnormal histological
      features (Liu et al., 1994; Dai et al., 1995). The histological alterations in
      HCM-affected hearts are characteristic, and can be used to diagnose the disease
      (Dai et al., 1995). Briefly, these are marked disorientation of cardiac muscle
      cells, thickening of the intramural coronary arterial wall with a narrowing of
      the lumen, endocardial and myocardial fibrosis. A high incidence of HCM in a
      population of pigs strongly suggests a hereditary basis and the Pig Research
      Institute, Taiwan has, therefore, endeavoured to produce a specific strain of HCM
      pigs. The purpose of the present study was to determine the ultrastructural
      changes occurring in pigs with naturally occurring HCM.

PMID- 8762610
TI  - Lipoprotein lipase activity of post-heparin plasma in Japanese black cattle
      affected with fat necrosis.
AB  - Post-heparin plasma (PHP) lipoprotein lipase (LPL) activity and serum lipoprotein
      concentration were examined in Japanese Black cows affected with fat necrosis.
      The PHP-LPL activity in the affected cows was significantly (P < 0.001) higher
      than in normal animals and tended to reduce 4 weeks after treatment with
      isoprothiolane. This finding indicates that affected cows have a predisposition
      to deposit more fat into adipose tissue than normal animals. The serum
      concentrations of triglyceride in beta-lipoprotein and of cholesterol,
      phospholipid and total lipid in alpha-lipoprotein were significantly (P < 0.05)
      lower in the affected cows. Elevated levels of phospholipid and total lipid in
      alpha-lipoprotein as well as decreased levels of non-esterified fatty acid (NEFA)
      were observed after medication. It is suggested that isoprothiolane produces an
      improvement in hepatic lipid metabolism including acceleration of plasma NEFA
      uptake and alpha-lipoprotein secretion in affected cows.

PMID- 8762611
TI  - Bovine leucocyte adhesion deficiency (blad) in a one year old Holstein Friesian
      bull--the first report in the United Kingdom.

PMID- 8762612
TI  - The incidence of luteal activity, as determined by peripheral plasma progesterone
      concentration, before the onset of the breeding season in the Rasa Aragonesa
      breed of sheep.

PMID- 8762613
TI  - [Emergent infectious diseases: a new problem?].
AB  - Are the emergent pathogenic microbes, persistent bacteria that have changed their
      virulence or new diagnostic techniques now allow their recognition? Or, have they
      found a new possibility of transmission due to ecological, social or cultural
      changes? The present Editorial analyses the geographical distribution, features
      and host factors that favor infections by Helicobacter pylorii, Enterohemorrhagic
      E. Coli, invasive Streptococcus pyogenes and Borrelia Burgdorferi. The
      surveillance and care of infections caused by emergent germs requires laboratory
      learning programs as those established in the United States.

PMID- 8762614
TI  - [CAA 19-9 and carcinoembryonic antigen in gallbladder cancer].
AB  - The aim of this work was to assess the diagnostic yield of serum tumoral markers,
      Ca 19-9 and carcinoembryonic antigen, in patients with gallbladder cancer. We
      studied 54 patients of whom 33 had gallbladder cancer and in 21 the tumor was
      removed previously and were presently free of disease. Twenty one patients with
      cholelithiasis were used as controls. Ca 19-9 was over 37 U/ml in 22 (65%)
      patients with cancer, in two patients free of disease and in two controls. The
      sensitivity and specificity of Ca 19-9 was 0.66 and 0.90 respectively.
      Carcinoembryonic antigen was over 2.5 ng/ml in 25 patients with cancer (56%) and
      its sensitivity and specificity was 0.75 and 0.71 respectively. Using a cutoff
      point of 4 ng/ml, these figures were 0.51 and 0.9 respectively. The better
      predictive capacity was given by a Ca 19-9 over 37 U/ml or a carcinoembryonic
      antigen over 4 ng/ml. It is concluded that, although the sensitivity and
      specificity of these markers was adequate in this work, one must bear in mind
      that studied patients had advanced tumors.

PMID- 8762615
TI  - [Prospective study of erradication of Helicobacter pylori in patients with
      duodenal ulcer: analysis of antral and gastric body biopsies].
AB  - Omeprazole may not eradicate Helicobacter pylori from the stomach but rather
      displace it from the antrum to the stomach body. This fact could interfere with
      colonization studies in patients receiving the drug. The aim of this study was to
      assess the presence of Helicobacter pylori, defined as a positive urease test,
      culture or microscopical examination, in antral and gastric body biopsies in
      patients receiving treatment with omeprazole. Sixty four paired antral and
      gastric body biopsies obtained at the end of a 28 day course of omeprazole, 62
      obtained four months later, 40 obtained eight months later and 23 obtained 12
      months later were analyzed. There was a 92% concordance between antral and
      gastric body biopsies for the presence of Helicobacter pylori. However, nine of
      the samples obtained at 28 days (14%) were negative for H pylori in the antrum
      but positive in the gastric body. It is concluded that for early assessment of
      Helicobacter pylori eradication after omeprazole treatment, paired biopsies of
      antrum and gastric body are needed.

PMID- 8762616
TI  - [Experience of a single center in liver transplantation in adults and children].
AB  - Orthotopic liver transplantation (THO) is the treatment of choice for a variety
      of liver diseases. The national experience before 1993 has been scarce. In
      November 1993 we started our experience in THO at Clinica Las Condes, as part of
      a multiorgan transplant program (liver, kidney, pancreas). Until January 1995 we
      have performed 14 THO in 13 recipients (one retransplantation), of which 5 were
      in pediatric cases. The recipients range of age fluctuated between 1 and 61
      years. In two pediatric cases a liver allograft reduction was performed. Six
      recipients (46%) required treatment for acute cellular rejection. One recipient
      had an hepatic artery thrombosis and had to be retransplanted. There was no
      operative mortality up to 30 days in cases of primary liver transplants. The
      retransplanted adult recipient, and another pediatric recipient that died from a
      late recurrence of a hepatoblastoma, accounted for the mortality of this
      experience. After an average follow up of 10 months, the actual patient survival
      in 85%. Of the 11 surviving recipients, 9 are in excellent conditions with a very
      good quality of life. This experience shows that an active liver transplant
      program in our country can be successful in obtaining results comparable to those
      published by very experienced foreign transplant centers.

PMID- 8762618
TI  - [Extracorporeal respiratory assistance. Experience in the treatment of severe
      acute respiratory failure].
AB  - Acute respiratory distress syndrome (ARDS) secondary to systemic injury has a
      high mortality. Symptomatic treatment with mechanical ventilation, PEEP and high
      levels of inspired oxygen is effective for most of the patients. When ventilatory
      support fails in reversing hypoxemia, extracorporeal respiratory assistance has
      been advocated as a temporary treatment until lung repair occurs. We described
      our experience in eleven patients (9M, 2F, 41 +/- 16 yo) with severe ARDS
      refractory to conventional treatment and expected to die if not assisted with
      extracorporeal oxygenation. All patients required invasive monitoring; seven
      needed continuous renal therapy because of concurrent renal failure. Venous
      venous percutaneous cannulation and systemic anticoagulation were performed and
      extracorporeal oxygenation and CO2 removal started with blood pump flows of 20 to
      30% of patient cardiac output. Improved oxygenation and decreased CO2 levels were
      immediately observed in 10/11 patients. One patient failed to have reversal of
      hypoxemia because recirculation and died shortly after initiation of
      extracorporeal therapy. Plasma leak syndrome and bleeding were observed in 3 and
      2 patients respectively. Extracorporeal assistance was maintained for 52 +/- 34 h
      (19-134). Five (45%) patients were weaned off the pump and two (18%) survived and
      were discharged. Despite the high cost, extracorporeal respiratory assistance,
      when applied to selected patients, can reverse hypoxia and may save some
      previously unsalvagable patients, allowing them to return to a normal life.

PMID- 8762617
TI  - [Surgical myocardial revascularization during the 1st 15 days of evolution of
      acute myocardial infarction].
AB  - Revascularization significantly improves early and late prognosis in acute
      myocardial infarction and has prompted substantial changes in therapeutic
      stategies. We report 140 patients aged 60.3 years old (123 male) operated within
      15 days of sustaining an acute myocardial infarction, between January 1984 and
      December 1989. Coronary angiogram showed single vessel disease in 8 (6%), double
      vessel disease in 32 (23%), triple vessel disease in 85 (61%) and left main
      vessel disease in 13 (9%). Indications for surgery were postinfarction angina in
      92 patients (66%), multiple severe coronary stenoses in 18 (13%), infarction of
      less than six hours from onset in 16 (11%), acute angioplasty failure in 7 (5%)
      and cardiogenic shock in 7 (5%). Thirty one patients were operated during the
      initial 24 h of infarction (16 with less than 6 h), 14 between the second and
      third day and 95 between the fourth and fifteenth day. Overall mortality was 4.3%
      (6/140). Among patients with failed angioplasty and cardiogenic shock, mortality
      was 23% (7/140), among patients with postinfarction angina this figure was 2.1%
      (2/92). No patient operated within 6 hours of infarction onset or due to severe
      coronary stenosis, died. Ninety seven percent of patients were followed during
      mean of 49 months. Three patients had a new acute myocardial infarction, two had
      sudden death and two died of unrelated causes. One required angioplasty and none
      was reoperated. Five years actuarial survival was 95% and the actuarial
      probability of being free of acute myocardial infarction, angioplasty or
      reoperation at five years was 99 and 100% respectively. It is concluded that
      early surgical revascularization in cute myocardial infarction is safe and has
      excellent long term results.

PMID- 8762619
TI  - [Congenital hip dislocation associated with spina bifida].
AB  - Spina bifida is commonly associated with hydrocephalus and feet malformations,
      however its association with congenital dislocation of the hip is not well
      document. We retrospectively analyzed the medical records of 120 children aged 6
      months to 15 years old, admited to a rehabilitation center with the diagnosis of
      spina bifida. Fifty six children (55.4%) had dislocation of the hip (36 of 53
      women and 20 of 48 men). These figures are higher than those reported for
      newborns by the Latin-American Collaborative Stud of Congenital Malformations. We
      conclude that congenital dislocation of the hip is frequent in children with
      spina bifida.

PMID- 8762620
TI  - [Delayed hypersensitivity to evoked antigens: normal values in Chilean young
      adults].
AB  - Delayed hypersensitivity skin test are widely accepted as in vivo measure of
      cellular immunity. Since genetic and environmental factors may affect these
      tests, each population must establish its own normal values. The aim of this work
      was to study delayed hypersensitivity in Chilean normal young adults. We studied
      the response to eight antigens using the Multitest CMI (Rhodia Merieux) in 50
      students (22 females, 28 males), aged 18 to 25 years old. Skin tests were read at
      24, 48 and 72 hours. At 48 Hours, 60% of women responded to 3 and 68% of men to 4
      antigens. A mean response to 3.6 antigens was observed. Total score in men and
      women were 19.5 +/- 7.3 and 12.2 +/- 6.5 mm respectively (p < 0.05). These
      figures are different from those published abroad and confirm the need for
      national standards.

PMID- 8762621
TI  - [Identification of Enterococcus species from clinical samples and their
      antimicrobial susceptibility].
AB  - The genus enterococcus has 12 species of which, E faecalis and E faecium are most
      important in human infections. A progressive resistance to penicillin and
      ampicillin has been detected in these species. The aim of this work was to
      identify Enterococcus species isolated in a hospital and to study their
      antimicrobial susceptibility. We studied 209 Enterococcus species coming from
      patients admitted to a public hospital. Their susceptibility to penicillin,
      ampicillin, imipenem, vancomycin, tetracycline, chloramphenicol, ciprofloxacin,
      gentamicin and streptomycin was determined with the agar dilution technique.
      Eighty seven percent of species were E faecalis and 7.1% were E fecium, other
      isolated species were E hirae, E casseliflaws, E avium, E solitarius and E
      faecalis variant. Thirty eight percent of these species were isolated from the
      urinary tract, 22% from the skin and 14% from surgical wounds. All E faecalis
      species were susceptible to penicillin, ampicillin, imipenem and vancomycin;
      27.3% were susceptible to tetracycline, 54.7% to chloramphenicol and 80% to
      ciprofloxacin. Seventy three percent of E faecium species were susceptible to
      penicillin, 80% to ampicillin and 60% to imipenem. Sixty two percent of E
      faecalis and 42.4% of E faecium were resistant to streptomycin. It is concluded
      that the correct identification of Enterococcus species has therapeutic
      implications.

PMID- 8762622
TI  - [Plasma concentrations and amiodarone/desethylamiodarone relations in patients
      subjected to chronic treatment].
AB  - We measured plasma concentrations of amiodarone and desethylamiodarone by HPLC in
      44 outpatients aged 24 to 67 years old (21 male), receiving the drug during at
      least three months. The drug was indicated for supraventricular arrhythmias in 37
      patients and ventricular arrhythmias in seven. Plasma concentrations of
      amiodarone, desethylamiodarone and their ratio were 1.71 +/- 0.82, 0.85 +/- 0.42
      micrograms/ml and 2.02 respectively, for a mean daily dose of 223 +/- 88 mg. In
      41 patients, arrhytmias were successfully treated. These patients received a mean
      daily dose of 220 +/- 86 mg and concentrations of amiodarone, desethylamiodarone
      and their ratio were 1.75 +/- 0.86, 0.88 +/- 0.45 micrograms/ml and 1.99
      respectively. In three patients with treatment failure, receiving a daily dose of
      257 +/- 115 mg, these figures were 1.2 +/- 0.3, 0.5 +/- 0.1 micrograms/ml and 2.4
      respectively. We conclude that our patients had lower plasma concentrations of
      desethylamiodarone and higher amiodarone/desethylamiodarone ratios than those
      reported in other countries.

PMID- 8762623
TI  - [Simultaneous pancreas-kidney transplantation. First cases in Chile].
AB  - We report two insulin dependent diabetic patients with a past history of 21 and
      30 years complicated with retinopathy, neuropathy and nephropathy with arterial
      hypertension and kidney failure. Simultaneous pancreas-kidney transplantation was
      done 8 and 18 months after starting hemodialysis, performing a double
      intraperitoneal implant with pancreato-duodeno-vesical anastomosis and
      contralateral kidney grafting with uretero vesical anastomosis using antireflux
      techniques. In the second case, a second kidney transplant from the same donor
      was needed, due to a thrombosis of renal vein. There was one rejection episode in
      each case but renal or pancreatic function was not impaired. Other observed
      complications were metabolic acidosis and hyperkalemia due to urine loss of
      bicarbonate, moderate arterial hypertension and bacterial and fungal infections.
      There was a graft dysfunction due to the association of vancomycin and
      cyclosporin. In conclusion, in the two presented patients, simultaneous pancreas
      kidney transplantations were successful and they remain free of insulin or
      dialytic therapy 4 and 9 months after the operation.

PMID- 8762624
TI  - [Acute abdomen due to mesenteric vasculitis as a presentation form of systemic
      lupus erythematosus].
AB  - We report a previously healthy 24 years old woman, that presented with an acute
      abdomen due to a mesenteric vasculitis. The diagnostic study demonstrated the
      presence of a systemic lupus erythematosus with a type IV nephropathy. Posterior
      to intestinal resection and immunosuppressive therapy, the patient had a
      satisfactory evolution.

PMID- 8762625
TI  - [Prolonged inhalation of nitric oxide in adult respiratory distress syndrome in a
      case].
AB  - Inhalation therapy with nitric oxide has been suggested as beneficial in the
      adult respiratory distress syndrome, however there are few reports of its
      prolonged use. We report a patient with a chronic lymphocytic leukemia that
      developed an adult respiratory distress syndrome with severe hypoxemia,
      refractory to conventional therapeutic measures, during the course of a septic
      shock. The patient received nitric oxide (19 ppm) improving arterial oxygen
      saturation and allowing the reduction of FiO2 to 40%. The patient died five days
      later due to a multiple organ failure.

PMID- 8762626
TI  - [Gonadal dysgenesis: diagnosis and therapeutic perspectives].
AB  - Ovarian dysgenesis is the endstage of a process of follicular atresia, Turner
      syndrome (45,X) being the most common cause, with an incidence of 1 in 2500
      female births. In addition to ovarian failure, these patients have short stature
      and a number of primary and derived somatic anomalies. Tertiary preventive
      measures are considered and treatment of short stature, estrogen deficiency and
      of infertility is discussed.

PMID- 8762627
TI  - [Ethical substrates behind social perception of medical performance].
AB  - Social perception of medical performance, although biased by emotional factors,
      prejudices of false interpretations, reflects people's expectations and
      satisfaction with medical acts. The violation of essential values by physicians,
      underlies the frequent disrepute of their professional behavior. Physicians are
      judged by their human behavior and relationships with patients rather than by
      their technical efficiency. The progressive medicalization of environment, the
      medical acts subjected to market laws, the conflicts of interest, the needs for
      accomplishment against diseases and the contradictory disarrangement of
      physicians behind health providing services, contribute to discredit and lack of
      confidence towards medical profession. To protect it against these risks, a
      profound revision of ethical principles is imperative.

PMID- 8762628
TI  - -Fetal growth in Chilean physiologic twins.

PMID- 8762629
TI  - [Bronchopulmonary cancer in workers exposed to arsenic: a case control study].
AB  - Case-control methodology was used to assess lung cancer risk from exposure to
      arsenic in air, employing data from former workers in different units at the
      Chuquicamata copper mine and smelter complex. Thirty two workers from this
      complex were identified among the lung cancer deaths that occurred in the
      Northern region of Chile between 1987 and 1991. Each case was matched on age and
      sex, with controls that had a similar date of enrolment in the company. Available
      data on arsenic concentrations in air for six work sites were compiled from 1952
      to 1991 and these were used to categorize the workplaces: Administrative area
      (1.6 micrograms/m3), Mine (2.3 micrograms/m3), Oxid Plant (3.1 micrograms/m3),
      Workshop and Services (9.8 micrograms/m3), Sulphur Plant (8.4 micrograms/m3) and
      Smelter (201.7 micrograms/m3). The results indicate an Odds Ratio of 5.7
      (Fisher's p = 0.016) of dying from lung cancer among workers of the smelter
      compared with the rest of the workers.

PMID- 8762630
TI  - [The contribution of Augusto Orrego Luco to Chilean psychiatry].
AB  - Augusto Orrego Luco born in 1848 and dead in 1933 in Valparaiso, was one of the
      greatest clinicians and researchers of chilean medicine during the late
      nineteenth and early twentieth century. Besides being a psychiatrist he
      contributed to literature, history, politics and medicine. He received his
      medical degree in 1874 and, apart from being an anatomist, soon became interested
      in mental illnesses. The title of his thesis was "Mental Hallucinations". He
      worked in the insane asylum after Jose Ramon Elguero. Later, in 1891, he was the
      successor of professor Carlos Sazie at the Hospital for Nervous and Mental
      Illnesses. Orrego Luco was influenced by french neurology of Jean Martin Charcot
      and taught a preferentially neurological psychiatry, based on the anatomo
      clinical method. His original works were on traumatic hysteria, the mechanism of
      hypnosis, hysterical hemiplegia, causes of mental hallucinations, syphilitic
      etiology of Tabes and anatomy of cerebral sulci. In his work about mimical
      neuroses, he considered and obligation not to discriminate between organic and
      non-organic patients, because both suffer, he claimed. Presently, Orrego Luco is
      considered the creator and instigator of the Psychiatry chair, turning it into
      one of the main medical specialties in Chile.

PMID- 8762631
TI  - Vibrio metschnikovii among diarrheal patients during cholera epidemic in Recife
      Brazil.
AB  - Although known since the last century, Vibrio metschnikovii was only
      appropriately described and recognized as a new species within the genus Vibrio
      in 1978. Rarely is the organism linked to human disease. Only once has V.
      metschnikovii been incriminated as responsible for human diarrhea, and affecting
      an old woman who suffered from diabetes and had a hepatoma. During the first two
      years of the present cholera epidemic, which reached Recife in March, 1992, we
      screened for vibrio nearly 4000 diarrheal fecal specimens submitted to a private
      clinical laboratory for detection of enteropathogenic microorganisms. Now, we
      report six cases of diarrhea associated with V. metschnikovii affecting
      individuals not suffering of any apparent underlying systemic illness.

PMID- 8762632
TI  - Species and serovars of enteropathogenic agents associated with acute diarrheal
      disease in Rosario, Argentina.
AB  - We report the most frequent species and serovars of enteropathogenic organisms in
      Rosario from 1985 to 1993. Enteropathogenic Escherichia coli was the most
      prevalent agent affecting 144/570 (25.2%) children; 0111 represented 41.8%, 055:
      13.6%, 0119: 12.7%. Among enterotoxigenic E. coli (ETEC) the most frequent were
      ETEC-ST 0128:H21 and 0153:H45. Shigella spp were isolated in 8.8%; S. flexneri:
      7%, principally type 2 (59.5%); S. sonnei: 1.6%, and S. dysenteriae type 2: 0.2%.
      Campylobacter spp were found in 6.1% of patients; C. jejuni: 4.6%; C. coli: 1.4%
      and C. lari: 0.2%; except groups 0 13.50 and 0 4 (2 cases each), no predominant
      serogroups were found. Salmonella was isolated in 2.8% of cases, being the
      predominant serovar S. typhimurium until 1986, but a dramatically increase of
      cases due to S. enteritidis was observed since 1987. There was 1.9% of Aeromonas
      spp and 2 cases due to Vibrio cholerae non 0-1. No Yersinia was found. In
      patients with gastroenteritis due to Shigella, Campylobacter, Salmonella, or EPEC
      as the unique pathogen, leukocytes were observed in the faeces in 70%, 50%, 20%,
      and 10% of cases respectively.

PMID- 8762633
TI  - Aerobic bacteria, Chlamydia trachomatis, Pneumocystis carinii and Cytomegalovirus
      as agents of severe pneumonia in small infants.
AB  - The authors studied 58 infants hospitalized for pneumonia in a semi-intensive
      care unit. Age ranged from 1 complete to 6 incomplete months. The infants were
      sent from another hospital in 20 cases and from home in a further 38. Pulmonary
      involvement, which was alveolar in 46 cases and interstitial in 12, was bilateral
      in 31 children. The investigation was carried out prospectively on the
      etiological agents associated with respiratory infection to look for evidence of
      aerobic bacteria (blood cultures), Chlamydia trachomatis and Cytomegalovirus
      (serology), and Pneumocystis carinii (direct microscopy of tracheal aspirated
      material). The following infectious agents were diagnosed in 21 children (36.2%):
      Aerobic bacteria (8), Chlamydia trachomatis (5), Pneumocystis carinii (3),
      Cytomegalovirus (3), Cytomegalovirus and Chlamydia trachomatis (1), Aerobic
      bacteria and Cytomegalovirus (1). Seven cases of infection by Chlamydia
      trachomatis and/or Cytomegalovirus were diagnosed out of the 12 cases with
      pulmonary interstitial involvement.

PMID- 8762634
TI  - Drug resistance of M. tuberculosis isolated from patients with HIV infection seen
      at an AIDS Reference Center in Sao Paulo, Brazil.
AB  - M. tuberculosis-positive cultures were obtained from 228 patients seen in our
      service and drug sensitivity assays were carried out from January 1992 to
      December 1994. A survey of the medical records of these patients showed
      resistance to one or more drugs in 47 (20.6%), 25 of whom (10.9%), who reported
      previous treatment, were considered to have acquired resistance. Among the
      antecedents investigated, only previous treatment and alcoholism were the factors
      independently associated with the occurrence of resistance. The survival of
      patients with resistant strains was lower than that of patients attacked by non
      resistant M. tuberculosis. We conclude that in the present series M. tuberculosis
      resistance to tuberculostatic agents was predominantly of the acquired type.

PMID- 8762635
TI  - Trypanosoma cruzi strains: behavior after passage into authoctonous or foreign
      species of traitomine (biological and biochemical patterns).
AB  - The behavior of T. cruzi strains from S. Felipe-BA (19 SF, 21 SF and 22 SF)
      classified as Type II Zymodeme 2, was investigated after passage through the
      authoctonous (P. megistus) and foreign vectors (T. infestans and R. prolixus).
      For each strain Swiss mice were infected: I--with blood forms (control); II--with
      metacyclic forms (MF) from P. megistus; III--with MF from T. infestans; IV--with
      MF from R. prolixus. Inocula: MF from the three species of triatomine, 60 to 120
      days after feeding in infected mice, adjusted to 10(4). Biological behavior in
      mice (parasitemia, morphology, mortality, virulence and pathogenicity) after
      passage through triatomine was compared with data from the same strain in control
      mice. Isoenzymic electrophoresis (ASAT, ALAT, PGM, GPI) were also performed after
      culture into Warren medium. The three strains maintained the isoenzyme profiles
      (zymodeme 2), in the control groups and after passages through different species
      of triatomine. Biological characterization disclosed Type II strains patterns for
      all groups. An increased virulence was observed with the 22 SF strain isolated
      from P. megistus and T. infestans and higher levels of parasitemia and
      predominance of slender forms in mice inoculated with the 19 SF and 21 SF from
      these same species. Results indicate that the passage through the two species T.
      infestans and P. megistus had a positive influence on the virulence of the
      regional strains of S. Felipe, regardless of being autocthonous (P. megistus) or
      foreign to the area (T. infestans).

PMID- 8762636
TI  - Population dynamics and biting rhythm of the anthropophilic sandfly Lutzomyia
      cruciata (Diptera: Psychodidae) in Southeast, Mexico.
AB  - Sandflies attracted by human bait were caught in an endemic focus of localized
      cutaneous leishmaniasis in the state of Campeche, Mexico. Catches were carried
      out monthly from February 1994 to January 1995 between 18:00 and 22:00 h.
      Lutzomyia cruciata was the only species caught. The highest population peak of
      Lu. cruciata was found in March with lesser peaks in February, December 1994, and
      January 1995. Maximum biting rate of Lu. cruciata was found between 18:00 and
      19:00 h. The host-seeking females of Lu. cruciata were directly related to levels
      of humidity between 88 and 100%. Low and high temperature had a negative effect
      upon Lu. cruciata activity. The possible role of Lu. cruciata as vector of
      leishmaniasis in the state of Campeche, Mexico is discussed.

PMID- 8762637
TI  - Etiological drug treatment of human infection by Trypanosoma cruzi.
AB  - Forty-nine American Trypanosomiasis (Chagas' disease) patients, with
      xenodiagnosis proven parasitemia were treated by the authors. Forty-one of these
      patients were given benznidazole, at dosages ranging from 5mg/kg/day to
      8mg/kg/day, during a pre-established period of 60 days. In this group, 17
      patients had an undetermined form of the disease, whereas 22 had cardiologic
      disease and 4 had digestive disease (two patients had a mixed form of the
      disease). Side effects were frequent, and led to the discontinuation of treatment
      in 17 patients. The follow-up period ranged from 1 to 20 years (mean follow-up
      period of 6 yrs. 7 mo). 26 (63.4%) of the patients became parasitemia-negative.
      The other eight patients were treated with nifurtimox, during 120 days, following
      a variable dose regime of 5mg/kg/day (initial dose) to 17 mg/kg/day (final dose).
      Six of them had severe side effects, and only one patient remained parasitemia
      negative throughout the observation period (ranging from 1 to 18 years).
      Benznidazole proved to be better tolerated and more effective in the management
      of parasitemia when compared to nifurtimox, although more effective and less
      toxic drugs are still desirable.

PMID- 8762638
TI  - Entamoeba histolytica: fecal antigen capture immunoassay for the diagnosis of
      enteric amebiasis by a monoclonal antibody.
AB  - Amebiasis continues to be of epidemiological importance in underdeveloped
      countries. Clinical diagnosis and epidemiological setting in a region are based
      on the fecal microscopic identification of cysts or trophozoites. This procedure
      requires well trained personnel, is laborious, of low sensitivity and frequently
      yields false-positives results. The present study was designed to develop an
      immunoenzymatic fecal 96 kDa antigen capture test (COPROELISA-Eh) more sensitive
      and specific than microscopic diagnosis of amebiasis. Triplicates of 177 stool
      samples processed by the formol-ether concentration method, were defined as
      positive or negative by three experienced microscopic observers. Another aliquot
      was submitted to the antigen capture test by a monoclonal antibody against a
      specific membrane antigen of pathogenic strains of Entamoeba histolytica. Optical
      densities were interpreted as positive when they exceeded the mean value of
      negative samples plus two standard deviations. COPROELISA-Eh showed a 94.4%
      sensitivity, 98.3% specificity, 96.2% positive predictive value and 97.6%
      negative predictive value for the detection of E. histolytica in feces.
      COPROELISA-Eh is more sensitive and specific than microscopic examination, does
      not require specially trained personnel and allows the simultaneous processing of
      a large number of samples.

PMID- 8762639
TI  - Intestinal spirochetosis: first cases reported in Brazil and the use of
      immunohistochemistry as an aid in histopathological diagnosis.
AB  - Colonization of the colon and rectum by intestinal spirochetes is detected for
      the first time in Brazil in 4 of 282 (1.41%) patients who had undergone
      sigmoidoscopy and/or colonoscopy with a histopathological diagnosis of chronic
      non specific-colitis. This frequency is probably underestimated, since surgically
      obtained specimens were not considered in the present study. Histopathological
      diagnosis was performed using routine stains like hematoxylin-eosin which showed
      the typical, of 3-microns thick hematoxyphilic fringe on the brush border of the
      surface epithelium, and by silver stains like the Warthin-Starry stain.
      Immunohistochemical procedures using two, polyclonal, primary antibodies, one
      against Treponema pallidum and the other against Leptospira interrogans serovar
      copenhageni serogroup Icterohaemorrhagiae cross-reacted with spirochetal
      antigen/s producing a marked contrast of the fringe over the colonic epithelium,
      preserving the spiral-shaped morphology of the parasite. In one case with marked
      diarrhea, immunohistochemistry detected spirochetal antigen/s within a cell in an
      intestinal crypt, thus demonstrating that the infection can be more widely
      disseminated than suspected using routine stains. Immunohistochemical procedures,
      thus, greatly facilitate the histological diagnosis of intestinal spirochetosis
      and may contribute to a better understanding of the pathogenesis of the disease.
      Transmission and scanning electron microscopy performed in one case showed that
      the spirochete closely resembled the species designated as Brachyspira aalborgi.

PMID- 8762640
TI  - Temporal association between the isolation of Sabin-related poliovirus vaccine
      strains and the Guillain-Barre syndrome.
AB  - Thirty eight paralysis cases classified as Guillain-Barre syndrome (GBS) in
      Brazil were analysed. In all these cases Sabin-related poliovirus vaccine strains
      were isolated. In most of the cases the last vaccine dose was given months or
      years before the onset of GBS, suggesting a persistent infection or the
      transmission of the Sabin-related strains to the patients. The isolation of Sabin
      related strains from GBS cases some days or weeks after the onset of the disease,
      demonstrated a temporal association between the isolation of the strains and the
      disease. Although the isolates from the GBS cases may not be the etiological
      agent of the disease, this study strongly indicates that infections caused by
      Sabin-related vaccine strains can trigger the GBS in certain cases.

PMID- 8762641
TI  - Malaria in the Indian reservation of "Vale do Javari", Brazil.

PMID- 8762642
TI  - Neostigmine in the treatment of snake accidents caused by Micrurus frontalis:
      report of two cases (1).
AB  - Antivenom in order to be effective in the treatment of coral snake accidents must
      be injected very soon after the bite owing to the rapid rate of absorption of the
      venom neurotoxins. As this is not always possible, other forms of treatment
      besides serotherapy must be employed to avoid asphyxia and death. Neostigmine and
      artificial respiration are used for this purpose. Neostigmine restores
      neuromuscular transmission if the venom-induced blockade results from a
      reversible interaction of its neurotoxins with the end-plate receptors. This is
      the mechanism of the neuromuscular blockade produced by the venom of M. frontalis
      snakes from centereastern and southern Brazil, and Argentine. Neostigmine is
      able, therefore, to antagonize the blockade, and has been shown to be very
      effective in the treatment of the experimental envenomation of dogs and monkeys.
      In the present communication, two cases of M. frontalis accidents treated with
      antivenom and neostigmine are reported. In both, neostigmine was successful in
      producing regression of the paralysis, confirming the effectiveness shown in the
      treatment of the poisoning induced in animals by M. frontalis venom.

PMID- 8762643
TI  - Hepatic fascioliasis: case report and review.
AB  - A well documented case of hepatic fascioliasis (HF), successfully treated with
      triclabendazole, is reported. Predominant clinical manifestations were fever,
      marked eosinophilia and abdominal pain. Triclabendazole was given as two single
      oral doses of 10 mg/kg each. Neither side effects nor clinical or parasitological
      relapses were seen after three months of follow up. Based on this experience and
      few other similar reports in the literature, triclabendazole might be a valid
      therapeutical alternative in the treatment of human fascioliasis.

PMID- 8762644
TI  - Diagnosis of acute toxoplasmosis in an immunocompetent patient by isolation of
      the agent and immunohistochemistry from lymph node biopsy.

PMID- 8762645
TI  - Is "wet lung" an iatrogenic syndrome? (proposal for an experimental study).

PMID- 8762648
TI  - [Longevity of Trypanosoma cruzi in the Triatoma infestans].
AB  - Maintenance of Trypanosoma cruzi infection in Triatoma infestans was evaluated.
      Seventy nine fourth instar nymphs were followed by 12 months, after being fed in
      infected mice. The bugs were examined every month, fecal smears were done to
      document T. cruzi infection then the bugs were fed in "clean" (uninfected) mice.
      Thirty nine per cent of the bugs remained infected until death twenty three per
      cent cleared infection and remained uninfected until death and nineteen per cent
      alternated positive and negative results. Our experience agrees with the
      published papers in medical literature. Longevity of T. cruzi in the host depends
      mostly in the feeding of the bug; well fed bugs maintain infection, and long
      fasting correlates with infection clearance.

PMID- 8762647
TI  - [Histomorphometric analysis of the bone tissue in patients with non-insulin
      dependent diabetes (DMNID)].
AB  - The effects of long-term diabetes mellitus on mineral metabolism and bone
      integrity remain ill defined. Several studies have shown that patients with
      insulin-dependent diabetes mellitus (IDDM) have reduced bone mass. However, the
      effect of non-insulin-dependent diabetes mellitus (NIDDM) on bone mass has been
      controversial. Quantitative histologic assessments were completed in iliac crest
      bone samples obtained from 26 patients (13 male and 13 female) with non-insulin
      dependent diabetes mellitus (NIDDM) and normal renal function (serum creatinine
      1.00 +/- 0.04 mg/dl). The mean age was 67.42 +/- 2.74 yrs, range 50-89 yrs. For
      the control group the bone samples were taken from 20 non-diabetic subjects (11
      male and 9 female) with a mean age of 57.95 +/- 3.96 yrs, range 33-91 yrs, n.s,
      that had suffered sudden or violent death. Significant lower values were present
      in the diabetic group for bone volume (p < 0.0001), osteoid volume (p < 0.005),
      osteoid thickness (p < 0.0001), cortical thickness (p < 0.05) and osteoblast
      surface (p < 0.05). Linear regression analysis revealed significant positive
      correlations of osteoid volume with osteoid thickness and osteoid surface in both
      groups. Our results suggest that the mechanism(s) underlying diabetic osteopenia
      may involve decreased bone turnover as reflected in a paucity of osteoblasts and
      diminished quantities of osteoid. A proeminent additional feature was a reduction
      in the cortical thickness.

PMID- 8762646
TI  - Prevalence of adult primary glomerular diseases: retrospective analysis of 206
      kidney biopsies (1990-1993).
AB  - The prevalences of the various histopathologic forms of primary glomerular
      disease (PGD) were evaluated by the retrospective analysis of 206 kidney biopsies
      performed in a three-year period (september 1990-september 1993) in patients
      between 14 and 73 years of age (107 men and 99 women). Data were compared with
      those of a study conducted in 1985-1987, on patients of the same age group. In
      the present study, primary glomerular diseases showed the following prevalences:
      focal glomerulosclerosis, 43.2%; membranous GN, 20.4%; membranoproliferative GN,
      14.1%; IgA nephropathy, 10.2%; minimal-change disease, 5.3%;
      mesangioproliferative GN, 2.9%; acute diffuse GN, 1.9%; rapidly progressive GN
      and proliferative focal segmental GN, 1% each one. Prevalences were similar in
      both sexes. Primary glomerular diseases were significantly more prevalent in
      patients with 35 years or less than in those up this age (64.6% vs 34.4%).
      Nonproliferative primary glomerular diseases were significantly more prevalent
      than the proliferative forms (68.9% vs 31.1%). The prevalences of the various
      histopathologic of PGD, with few exceptions, were about similar in the periods
      1985-1987 and 1990-1993: the prevalences of focal glomerulosclerosis, membranous
      GN, IgA nephropathy and mesangioproliferative GN showed no significant
      differences; the prevalence of membranoproliferative GN increased (6.8% vs
      14.1%), but that of type II remained very low (0.5%). Focal glomerulosclerosis
      was the most prevalent PGD. The prevalence of IgA nephropathy remained low,
      comparable with the smallest prevalences found in some of the Western countries.

PMID- 8762649
TI  - [Pulmonary lesion in electric injury: report of a case].
AB  - Major electrical injuries constitute approximately 5% of all admissions to Burn
      Units. Visceral complications are associated with a high mortality rate. The most
      common visceral lesions associated to electric burns are cardiac lesions.
      Pulmonary compromise is rare, if compared to inhalation injuries in termical
      burns. Although, when the entry or exit ports are the toracic wall, pleural
      effusion, hemotorax and pneumonitis may occur. A rare case of high-voltage
      electrical injury with massive pulmonary lesion is presented, regarding to
      clinical course and roentgenographic patterns.

PMID- 8762650
TI  - [Autosomal dominant polycystic kidney].
AB  - A 48-year-old male had autosomic dominant polycystic kidneys with dimensions, to
      the best of our knowledge, never previously reported; the right kidney weighed
      15,100 g and measured 53 x 33 x 9cm and the left one 10.200 g and 46 x 21 x 7cm,
      with cysts measuring up to 14cm in diameter. Nephrectomy was done to control
      persistent hematuria and to relief disconfort caused by the large kidneys. The
      renal function is stable four years after transplantation.

PMID- 8762651
TI  - [The role of the polymorphonuclear neutrophil in the failure of multiple organs
      and systems].
AB  - The role of the polymorphonuclear neutrophil (PMN) on MOF is analyzed either as
      PMN activation for superoxide and enzyme release, or as PMN function depression
      after trauma and surgery. The authors stress: 1) the signal transduction pathway
      from the PMN membrane receptors to the effector response; 2) the PMN-NADPH system
      structure and function; 3) the functional states of the PMN (quiescente, primed,
      activated, non-responsive) in terms of the NADPH system activation; 4) the
      mechanism of tissue injuiry by the PMN. Clinical investigations on the PMN
      activation state, and therapeutical goals based on recent clinical investigations
      are also discussed.

PMID- 8762652
TI  - [Bacterial infections in patients with acquired immunodeficiency syndrome (AIDS).
      Review of literature].
AB  - The incidence of patients infected by HIV is increasing in almost country of the
      world with a simultaneous increase of bacterial infections in these patients. The
      clinical presentation of bacterial infections is similar to that observed in
      immunocompetent patients yet more prolonged, recurrent and often more severe, as
      well as the infection may be by some unusual bacteria. Specific antibicrobial
      therapy is usually effective, but recurrences are frequent.

PMID- 8762653
TI  - [Evidence-based medicine].
AB  - Evidence-based medicine has been described as a new approach to teaching and
      practicing clinical medicine. Although the search for evidence is an established
      practice among physicians, what is being proposed is the systematic gathering and
      critical interpretation of data, which can then be used in the appropriate
      context. The main objective is to provide better care for patients. This is
      accomplished by transforming clinical problems in specific questions to be
      answered by searching the literature for the levels of evidence favoring the
      possible interventions for one particular case. This has to be done in a
      systematic and conscientious fashion. Through its method, evidence-based medicine
      places less value on clinical experience, the study understanding of
      pathophysiology, and common sense; instead, it emphasizes observation, levels of
      evidence, and critical interpretation of original literature. In this manner,
      evidence-based medicine may be seen by the authoritarian physician as a threat.
      Other obstacles to the acceptance of the method include lack of time and lack of
      familiarity with computers. One important limitation of evidence-based medicine
      is the incomplete or contradictory evidence available in many areas of clinical
      medicine, or the so-called "grey zones". We outline the main aspects of evidence
      based medicine, expecting a growing interest among brazilian physicians for this
      useful clinical tool.

PMID- 8762654
TI  - [Viral hepatitis type A. Who should be vaccinated?].
AB  - In order to find out the variations in the Prevalence of HAV ab and identify the
      persons who should be vaccinated against Hepatitis A virus, we assessed HAV ab to
      200 patients without any occupational risk. They were classified by their
      socioeconomic status; in the following categoris: High (level I n = 0); Medium
      High (level II n = 50); Medium-Low (level III, n = 50); Low (level IV, n = 50);
      and Very Low (level V, n = 50). The percentage of positivity ofr serum HAV ab
      was: Level II: 12%, Level III: 18%, Level IV: 38% and Level V: 40%. The
      difference between levels II and III and between levels IV and V was no
      significant (p > 0.05), but after making a comparation between levels II and III
      as a group and levels IV V as another one, we found a statistical significant
      difference (p < 0.005). We concluded: There is a bimodal behavior for the
      prevalence of serum HAV ab in our study: one group with high prevalence (78%) and
      another one with low prevalence (30%). The massive Vaccination government
      programs and the vaccionation in particular cases in the daily medical practice
      should be done after assessing the personal Socioeconomic status in order to
      improve the use of this tool and achieve a progressive reduction in the morbiditi
      and high endemicity of HAV in our city.

PMID- 8762655
TI  - [Rectal biopsies from HIV-infected patients].
AB  - Rectosigmoidoscopy and rectal biopsies specimens were taken from thirty six HIV
      infected patients in the Vargas Hospital of Caracas. There were thirty three
      males and three females. the mean age was thirty two years. Seventy three per
      cent were homosexuals. The sexual behaviour was the most important risk factor
      for the infection with the HIV. Forty four per cent of the rectosigmoidoscopies
      were abnormal, presenting hiperemic or petechiae mucosas. Alterations in rectal
      biopsies were reported on all specimens, twenty six with inespecific chronic
      rectitis. Two bipsies reported Kaposi's Sarcoma and eight bipsies demonstrated
      opportunistic agents.

PMID- 8762656
TI  - [Leptospirosis in Gastroenterology. Study of 14 cases in the Hospital
      Universitario de Caracas 1984-1994].
AB  - 14 cases that were admitted to the Hospital Universitario de Caracas, between
      1.989 and 1.994, with a definitive diagnosis of Leptospirosis by
      microaglutination of live antigens were studied. Most of them hospitalized at the
      gastroenterology service. The serovar most frequently found was icterohemorragiae
      11 cases. There was a predominium for the male gender 12/2 and the majority of
      patients belonged to the range of age between 31 and 40. The most common forms of
      presentations were: fever (14), jaundice (10) and myalgias (10) while the most
      relevant findings at physical examination were: jaundice (12), fever (11) and
      hepatomegaly (8). All patients had abnormal laboratory tests and among these,
      aminotransferases, bilirrubin, creatinin, CPK, platelets and urinary sediment
      were more frequently altered. Only half of the patients were diagnosed as
      Leptospirosis at the moment of admission. We conclude that even though
      Leptospirosis is an infectious disease distributed worldwide only few cases are
      hospitalized and differential diagnosis is difficult because of diversity of
      clinical presentations and lack of laboratory resources. It is important for
      gastroenterologists because most of complicated cases present as jaundiced
      patients.

PMID- 8762657
TI  - [Percutaneous endoscopic gastrostomy in patients with head and neck neoplasms.
      Evaluation of a new gastrostomy].
AB  - Since their aparition in 1980, percutaneus endoscopic gastrostomy (PEG),
      represented a dramatic impact in the enteral nutrition thecnics and their
      indication have expanded. The PEG have many advantages over the surgical
      gastrostomy. In this paper, we present our experience with the use of PEG in
      patients with head and neck cancer using a new home made gastrostome. Included
      were 61 patients 37 males (64.8%), 21 females (36.2%) with ages betwen 11 and 72
      years. In 3 patients the PEG was not intended because tight esophageal stenoses.
      The PEG was completed in 56 cases (91.8%). In 5 patients (8.6%) there were minor
      complications (4 infections and 1 patient with pain). We have only one case of
      major complication which consisted in migration of gastrotome to the abdominal
      wall (Buried Bumper Syndrome). The gastrostome was patent between 15 and 312 days
      with a median of 125 days. The gastrostomies was made with siliconed 22Fr Foley
      catheter, crazy glue, and plastic tops. The Foley catheter is acid resistant and
      not deteriorate like other materials like latex. There was not adverse reaction
      at the ostomy site. The cost of the kit is about 11 US$ and the commercial kit is
      125 US$, on the other hand the internal diameter is 15% wider than the commercial
      one.

PMID- 8762658
TI  - [Intrahepatic lithiasis].
AB  - The intrahepactic lithisis is unusual in the Occidental hemisphere. The
      prevalence in Venezuela in unknown. We study all the edoscipic retrograde
      cholangiography carried for lithiasic pathology, in the Servicio de
      Gastroenterologia, Hospital Universitario de Caracas, since January 1993 until
      April 1995. Over 342 patients, 9 were intrahepatic lithisis (1.16%). Seven cases
      of Caracas and two refered of the rest of the country. The sex was female in
      seven patients and males in two. The age range was 15 to 67 years old. The clinic
      feature much frequent was abdominal pain. The diagnosis was ultrasound and
      endoscopic retrograde cholangiography. The treatment was endoscopic with
      sphincterotomy and removal stones and surgical with resection in two cases, and
      choledocotomy in the other four cases.

PMID- 8762659
TI  - [Evaluation of methods for the diagnosis of Helicobacter pylori infection].
AB  - Helicobacter pylori is a gram negative curved bacillus recognized as etiologic
      agent of chronic gastritis and an important factor in the development of duodenal
      ulcer and gastric cancer. The purpose of this work is to evaluate three
      microbiologic methods for diagnosing H. pylori infection. We studied 375 samples
      from 218 patients, who consulted at the Department of Gastroenterology of the
      Hospital Vargas and were candidates for endoscopy. Samples of gastric mucous
      tissue were taken at level of the antrum and each sample was stained with Gram,
      tested for urease and cultured. RESULTS: whit H. pylori positive 123 patients
      with duodenal ulcer at the endoscopy (91.1%), 17 had gastric ulcer (76.5%), 40
      gastritis and/or duodenitis (60.0%), 1 duodenal ulcer and gastric (100.0%) and 37
      normal endoscopies (56.8%). Evaluating the three methods used we found that of
      the 286 H. pylori positive samples, the Gram stain detected 282 (sensibility
      98.6% and specificity 96.6%); the urease test 276 (sensibility 96.5% and
      specificity 98.6%) and culture was positive in 255 samples (sensibility 89.2% and
      specificity 100.0%). These results show that both the Gram stain and Urease test
      are useful for diagnosing H. pylori infection due to their high sensitivity and
      specificity, rapidness, low cost for the Gram stain, and easy interpretation for
      Urease test. Culture, even though less sensitivity++, represents the most
      unquestionable diagnosis and permits carrying out susceptibility to
      antimicrobials tests.

PMID- 8762660
TI  - [Effectiveness and innocuousness of the association of calcium dobesilate,
      dexamethasone acetate and lidocaine versus prednisolone capronate with dibucaine
      clorohydrate in the treatment of hemorrhoids-].
AB  - The objective of the present study was to compare properties of two associations
      in the topical treatment of hemorrhoids. They were included 40 patient with
      diagnosis of internal hemorrhoids grade 1 or 2, which was indicated topic
      treatment after the realization of an interrogatory and anoscopy. The treatment
      received according to a randomized and double blind design: A = dobesilate of
      calcium with acetato of dexamethasone and lidocaine or B = Capronato of
      Prednisolone with Clorhidrato of dibucaina, applied twice a day. They were
      carried out controls every 7 days. In each control was carried out interrogatory
      and respective anoscopy. There was a prevalence of the females, and the age
      corresponded to the 5t decade of the life. Patients of the treatment. A presented
      greater number of predisponents factors, but minor percentage of previous
      treatments. As for the evaluation of the punctuation of symptoms and of the grade
      of Hemorrhoids, comparing beginning and final, they didn't show significant
      difference interproduct confirming the effectiveness and similar inocuity. In
      both products was observed a important improvement concerning to the symptoms and
      grade of hemorrhoids but the patients of the treatment A precipitated the greater
      speed. As for the evaluation made by the phisicians, the treatment A (88%) and B
      (85.7%) the got successful outputs. The opinion of the patients was a 100% of
      marked goods or moderated beneficial. Both treatments were successful so much in
      effectiveness like in inocuity although the treatment A were always got the best
      efectiveness outputs.

PMID- 8762661
TI  - [Von Recklinghausen disease and hepatic neurofibromatosis].
AB  - Von Recklinghausen's neurofibromatosis is one of the most common autosomal
      dominant disease with an estimated frecuency of 1:3000 live births.
      Characteristic lesions include cafe-au-lait spots and neurofibromas following the
      path of peripheral nerves. Liver involvement by neurofibromatosis is rare and
      very few cases have been reported. We present a case of a young man with Von
      Recklinhausen's disease and hepatic neurofibromatosis with multiple caf-au-lait
      spots, cutaneous neurofibromas, short stature and osseous lesions and compare the
      clinical, radiological, surgical and anatomopathological findings with others
      describe previously in the literature.

PMID- 8762662
TI  - [Primary intestinal lymphangiectasia in children. Report of 3 cases].
AB  - It report three cases of Primary Intestinal Lymphangiectasia that presented the
      common symptoms of diarrhea, oedema and hipoalbuminaemia in which we could
      observed the clinics variations that can to present this entity. It demonstrated
      the importance of the intestinal biopsy to get a correct diagnosis just as the
      essencial of use of the medium chain triglycerides with the restriction of the
      common fast, to recuperate these patients.

PMID- 8762663
TI  - [Gastrointestinal stromal sarcoma. Report of a case and review of the
      literature].
AB  - The present report describes a case of a 27 year old patient with epigastric pain
      of moderate intensity, accompanied by hiporexia, weight loss and melena who was
      hospitalized in August 1.994 after 17 days of these signs and symptoms.
      Colonoscopy revelead a 6 cms polypoid, ulcerated lesion in the hepatic angle of
      the colon. At surgery, a 5 x 5 cms tumoral lesional 1.5 cms from the Treitz
      adhered to the small bowel was found. The gross findings of the specimen revealed
      an exophitic ulcerated tumor that measured 10 x 10 x 9 cms. Satellite nodules up
      to 2 cms in diameter were seen in contact with the large bowel mucosae. Light
      microscopy, immunohistochemical and ultrastructural studies, indicated a
      diagnosis of PLEXOSARCOMA.

PMID- 8762664
TI  - [Early gastric cancer in the remnant stomach. Case report].
AB  - Patients with partial gastrectomy are a High risk group to develop gastric
      cancer. Risk is higher in remnant estomach after partial gastrectomy by
      malignancy than benign disease. We present a case of a male patient, 64 years
      old, who was admitted in our Hospital with Hypovolaemia. We found during
      Endoscopic examination early gastric Cancer IIc + III type in the site of
      anastomosis. Partial gastrectomy was performed in this patient by Duodenal ulcer
      11 years ago.

PMID- 8762665
TI  - [Hemochromatosis: frequent but few times diagnosed].

PMID- 8762666
TI  - Tropical diseases research.

PMID- 8762667
TI  - [Qualitative and quantitative study of Taenia solium posoncospheres in the
      muscular tissue of pigs with and without cysticercosis].
AB  - It was determined the presence of posoncospheres in muscular tissues in 20
      natural cysticercotic pigs and in 20 pigs apparently free of Taenia solium
      metacestodes. Ten differents anatomical regions were dissected, giving 400
      samples in total. The animals were slaughtered in Ecatepec, Mexico State, Mexico.
      The samples were kept in bottles with saline and were processed in the
      Laboratorio de Biologia de Parasitos, Facultad de Medicina, Universidad Nacional
      Autonoma de Mexico (UNAM); cysticercus were counted and later on the resulting
      muscular mass was grinded and observations were made in the sediment, for
      posoncospheres search. Mann-Whitney statistical method revealed meaningful
      differences between postoncospheres in cysticercotic pigs and not apparently
      cysticercotic pigs. The Linear Correlation Analysis showed no relation between
      cysticercus quantity and postoncospheres quantity in the same samples.
      Postoncospheres were found in cysticercotic animals and in those apparently free
      of cysticercus, in the last group the quantity was bigger.

PMID- 8762669
TI  - [Prevalence of protozoa infections in synanthropic rodents in Valdivia City,
      Chile].
AB  - In order to determine the prevalence of infection by blood and intestinal
      protozoa in 57 synanthropic rodents from Valdivia city, a study was carried out
      in the period march-september 1986. The group of rodents studied was constituted
      by 31 Mus musculus, 19 Rattus rattus and 7 Oryzomys longicaudattus, being 42
      males and 15 females. Diagnostic forms of protozoa were found in 70.2% of the
      investigated animals. The presence of five species of enteroprotozoa and one
      species of hemoflagelate was detected. The number and the corresponding
      percentages of infected animals were the following: Giardia muris, 21 (36.8%),
      Hexamita muris, 22 (38.6%), Trichomonas muris, 27 (47.4%), Entamoeba muris 9
      (15.8%), Eimeria sp. 15 (26.3%) and Trypanosoma lewisi 9 (15.8%). Not significant
      differences were observed when considering host or sex of the species found
      infected. Furthermore, the yielding of fecal examination considering direct
      examination, sugar solution flotation and SAFS were compared. The sugar solution
      flotation technique showed the highest percentage diagnosis of coccidia, whereas
      SAFS was more efficient for detecting G. muris and E. muris.

PMID- 8762668
TI  - [Intestinal geohelminthosis in man and domestic animals in the riverside sections
      of the Valdivia River Basin, Chile].
AB  - In March-October 1987 were analyzed 1295 coprological specimens in a sample of
      the human population who lives in riverside localities in the Valdivia River
      Basin, Chile. A 23.6% of examined persons presented infection by one or more
      helminth species. The prevalence of infection by Ascaris lumbricoides, Trichuris
      trichiura and Trichostrongylidae gen. sp. were 15.5, 12.7 and 0.2%, respectively.
      The prevalence of human ascariosis and trichuriosis were greater in pre-school
      and school children. The sex of the host and prevalence of geohelminthosis did
      not show any relationship. Prevalences of ascariosis and trichuriosis were higher
      in persons from houses with no sanitary fecal and water disposal. Over 35% and
      20.7% of family groups showed infection by A. lumbricoides and T. trichiura,
      respectively in over 40% of the members of each group. Fecal samples from
      domestic mammals revealed the following prevalences rates for helminth
      infections: in dogs 19.0 and 15.2% for Toxocara canis and Uncinaria stenocephala
      respectively, in cats 65.1% for Toxocara cati, and in pigs 25.4 and 3.2% for
      Ascaris suum and Trichuris suis respectively. Some of these species are clearly
      demonstrated agents of zoonoses.

PMID- 8762670
TI  - Studies on the new species Tylocephalum chiralensis, parasite from Dasyatis
      (Himantura) uarnak (Forskal) from Chirala coast, Andhra Pradesh, India.
AB  - A new species of the cestode genus Tylocephalum obtained from the host Dasyatis
      uarnak is described. A detailed examination of specimens have allowed us to erect
      a new species Tylocephalum to accommodate the worm. It shows remarkable
      differences from other known species of Tylocephalum in large size of the worm,
      absence of neck, variation in number of testes arrangement of vitellaria and
      genital openings. The new species is designated as Tylocephalum chiralensis.

PMID- 8762671
TI  - [Presence of Triatoma spinolai in human dwellings].
AB  - Triatoma spinolai is a wild species of triatomine existing exclusively in Chile,
      with scarce epidemiological importance in the transmission of Trypanosoma cruzi
      to man. It has been found in environments from 3000 meters down to the sea level.
      Exceptionally it has been found in human dwellings. In order to clarify the
      possibility of an adaptation of T. spinolai to human dwellings a study was
      undertaken in 50 rural-periurban dwellings from regions III, IV, V and
      Metropolitan in which this triatomine was found. The dwellings were classified in
      houses (35) and huts (15). The insect was trapped in 35 dwellings (24 houses and
      11 huts) located in declivities (70%) and 15 dwellings (14 and 1) located in
      plains. This proportion is significantly higher than the average of 26.2% for
      dwellings located in declivities. It is concluded that the presence of T.
      spinolai in dwellings, more than a triatomine invasion is the result of the
      construction of huts or houses in the insect habitat.

PMID- 8762672
TI  - [Taenia sp and other intestinal cestode infections in individuals from public
      outpatient clinics and hospitals from the northern section of Santiago, Chile
      (1985-1994)].
AB  - During 1985-1994 period, 70,642 parasitological stool examinations were
      performed. The exam was made to each patient which presenting gastrointestinal
      symptoms or nutritional problems, specially in children. 59,960 out of the 70,642
      examinations corresponded to 1 month--15 years old children, 4,280 to 16-30 years
      old individuals and 6.402 to up to 30 years old adults. The infection rates (x
      100,000) were: Taenia sp., 86; Hymenolepis nana, 1,165; Diphyllobotrium sp., 4
      and Hymenolepis diminuta, 1. In this period, 11 cases of infection by Taenia
      saginata were detected, and none Taenia sodium infection. Although infections
      rates by intestinal cesdodes were higher in males than females, in the Taenia sp.
      infection the difference was not statistical significative. Medico-veterinary
      control of animals slaughtered in abbatoirs and the improvement of sanitary
      conditions in the last two decades have contributed to the control of most of
      human intestinal cestodiases.

PMID- 8762673
TI  - [Epidemiology of Chagas disease in Chile. Frequency of human Trypanosoma cruzi
      infection by age groups and regions].
AB  - Chagas' disease is endemic in rural-periurban sections of the northern half of
      Chile which includes the first seven political-administrative regions of the
      country (18 degrees 30'-34 degrees 36' South lat.). Data concerning to the
      results of an indirect hemagglutination test for Chagas' disease performed to
      15,418 rural-periurban and 45,119 urban inhabitants fron the chagasic endemic
      regions are presented. Migrations from rural-periurban to urban areas have
      contributed to the dissemination of Trypanosoma cruzi infection. General rates of
      infection for rural-periurban (r-p) and urban (u) sections were 16.7% and 1.9%
      respectively. The higher prevalence rates were detected in Region III with 27.2%
      (r-p) and 3.9 (u) and Region IV with 24.7% (r-p) and 3.5% (u), while the lower
      prevalence rates corresponded to Region VI with 7.0% (r-p) and 0.8% (u).
      Serological positivity increased parallelly with age in all regions.

PMID- 8762674
TI  - [Evaluation of a triatoma infestans eradication program in rural dwellings from
      the IV region, Chile, by means of serology for Chagas disease in 0-10 years old
      children].
AB  - The present study deals with the evaluation of the effectiveness of the measures
      employed in the control of Triatoma infestans, the vector of Trypanosoma cruzi
      infection (Chagas' disease), in the IV region of Chile through a serological
      follow up program. For this reason, a serological survey has been carried out in
      2,783 children, from 0 to 10 years, who live in rural high endemic areas of the
      region. The sera were tested using an indirect hemagglutination test (IHAT) and
      ELISA techniques with results agreeing in 99.9% of the samples. In children with
      positive serology xenodiagnosis was performed and blood samples from the
      corresponding mothers were submitted to serology for Chagas' disease. These
      additional tests should allow to distinguish between congenital infection and
      vectorial transmission. It was observed that vectorial transmission of T. cruzi
      was interrupted in some localities where entomological control has been applied
      for 10 years, or lowered in those which have been submitted to desinsectations in
      the last 5 years. On the other hand, a relatively high prevalence of the
      infection has been detected in some localities. These results suggest an apparent
      increase of vectorial transmission, indicating the need of readjusting the
      dwellings insecticide sprayings activities to improve the measures against the
      vector.

PMID- 8762675
TI  - [Diagnostic valve of ELISA-IgG for trichinosis using Melcher's antigen].
AB  - An enzyme-linked immunosorbent assay (ELISA) for trichinosis using a Melcher's
      antigen was developed for the detection of IgG antibodies in 41 serum samples
      from patients confirmed or suspected to have trichinosis by strong clinical and
      epidemiological evidences. ELISA- IgG was compared with a precipitin test (PT), a
      bentonite floculation test (BFT) and an indirect hemagglutination test (IHAT).
      The cut-off value was determined using serum samples from 67 apparently healthy
      persons employing two serum dilutions (1:100 and 1:500) with three standard
      deviations (SD). The sensitivity of ELISA- IgG was 97.6% and 95.2% using serum
      dilutions of 1:100 and 1:500 respectively, whereas the values for the other tests
      were: PT (92.7%), BFT (63.4%) and IHAT(85.4%). According to MacNemar test, ELISA
      IgG did not present statistical significance (p > 0.05) compared with PT and
      IHAT, whereas all of them were different compared with BHT (p > 0.01). In order
      to find out the specificity of ELISA-IgG, additional 124 serum samples from
      individuals with other parasitoses, such as cysticercosis (31), fascioliasis
      (17), hydatidosis (51) and toxocariasis (25) were also tested. ELISA-IgG
      presented a specificity of 99.5% with both serum dilutions. The positive
      predictive values were 97.6 and 97.5%, whereas the negative one were 99.5 and
      99.0% for 1:100 and 1:500 serum dilutions respectively. The use of ELISA-IgG and
      Melcher's antigen in the diagnosis of human trichinosis is discussed.

PMID- 8762676
TI  - [Comparison of 3 techniques in the serological diagnosis of human hydatidosis].
AB  - Three serological techniques for hydatid disease were compared using 60 human
      serum samples obtained from 29 patients with hydatidosis previously demonstrated
      by surgery, 15 apparently healthy individuals and 16 persons with different
      pathologies. The results obtained with these 3 techniques showed some differences
      that could associate with the anatomical location of the parasite and the
      biological stage of the hydatid cysts. The global sensitivity of the techniques
      was 96.6% for ELISA, 86.2% for IHAT and 79.3 for DD5. False positive reactions
      were observed with IHAT and ELISA in sera from patients with infection by Taenia
      saginata. ELISA also showed cross reactions in the sera of four patients with
      intestinal infection by Ascaris lumbricoides. No false positive reactions were
      observed with DD5 test.

PMID- 8762677
TI  - [Phalocrocorax olivaceus (Aves: Phalacrocoracidae), a new vector of Henneguya sp.
      in aquatic ecosystems from southern Chile].
AB  - This is the first report of Henneguya sp., a myxozoan parasite of fishes, in
      faeces of Phalacrocorax olivaceus, a piscivorous bird, from Valdivia river, Chile
      Phalacrocorax olivaceus would be a mechanical vector of Hennguya sp. and
      contributes to disseminate the infection in fishes.

PMID- 8762678
TI  - [Intestinal inflammatory disease and smoking].

PMID- 8762679
TI  - Betel nut and smoking. Are they both protective in ulcerative colitis? A pilot
      study.
AB  - Two-hundred and twenty-three Asian patients with inflammatory bowel disease were
      sent a questionnaire about smoking and betel nut chewing habits. The 116
      responses from patients with ulcerative colitis were compared with answers from
      79 healthy members of the community. Twelve per cent of male patients were
      currently smokers compared with 31% of healthy controls (chi 2 = 20.9 P < 0.05).
      No such differences existed between female patients and controls. Thirteen per
      cent of male patients regularly used betel nut compared with 20% (chi 2 = 3.9 P <
      0.05). Both smoking and betel nut chewing appear to reduce the risk of developing
      ulcerative colitis, although these effects may be linked.

PMID- 8762680
TI  - [Surgical treatment of solitary liver cysts].
AB  - Solitary hepatic cysts an uncommon disease in the past, which incidental
      diagnosis is increasing with the advent of ultrasound and computed tomography,
      are nowadays very frequent. Cysts that reach massive proportions often become
      symptomatic and necessitate surgical intervention. Surgical wide unroofing
      technique is a simple procedure advocated for the treatment of symptomatic
      patients. Ten patients with solitary liver cysts were submitted to wide unroofing
      with good immediate and late results.

PMID- 8762681
TI  - [Lactose absorption and tolerance to different types of yogurts in adults with
      hypolactasia].
AB  - It is known that lactose is better absorbed in yogurts than in milk by lactase
      deficient individuals. This fact is due to the presence of beta-galactosidase
      activity in the yogurts, that are different concerning the caracteristics of the
      products. Thus, the aim of this study was to verify the absorption and tolerance
      of lactose in some yogurts consumed by our population. We studied 12 hypolactasic
      adults who, after diagnostic confirmation, were submitted to three breath
      hydrogen tests after ingestion of milk and two yogurts with different levels of
      beta-galactosidase. These activities were determined in each sample utilized. The
      lactose absorption was evaluated by the measurement of H2 eliminated in the
      expired air and the tolerance was assessed by the symptoms reported by the
      participants. The medians of the H2 maximum increment were 20 ppm/min for the
      milk, 10.5 for yogurt X and 5.5 for the yogurt Y. The area under the curve of H2
      concentration presented a median of 960 in the test with milk, 420 with yogurt X
      and 270 with yogurt Y. These results showed statistically significant differences
      for milk and the two yogurts and similar among the yogurts. The score for
      symptoms also were different between the milk and the two yogurts and similar
      among the yogurts. A statistically significant association between absorption and
      tolerance was not observed, because many tolerant subjects were malabsorbers of
      lactose. These data show that lactose in yogurts is better absorbed and better
      tolerated than lactose in milk, suggesting that our products are similar to those
      of the literature concerning their capacity of hydrolising lactose "in vivo". In
      spite of the differences found "in vitro" among the beta-galactosidase, there
      were no significant differences of absorption and tolerance between the two
      yogurts studied.

PMID- 8762682
TI  - [Surgical treatment of megaesophagus. Effect of myotomy and fundoplication on the
      lower esophageal sphincter].
AB  - Details about the structure of the lower esophageal sphincter and the function of
      fundoplication are yet unknown. New study is presented about electromanometric
      examination of the lower esophageal sphincter in 20 chagasic patients with
      megaesophagus operated on by cardiomyotomy complemented with His angle
      agudization (Group A-10 patients) or fundoplication (Group B-10 patients). On the
      30th postoperative day, the patients, without dysphagia, were submitted to
      radiologic study, demonstrating valvuloplasty integrity (Group B), and
      electromanometric study of the esophagus. The comparison between the groups
      demonstrated: -myotomy does not modify the lower esophageal sphincter extension,
      but decrease its pressure, not to zero; -fundoplication does not increase the
      lower esophageal sphincter pressure after myotomy, under resting conditions.
      These conclusions suggest that: -lower esophageal sphincter is formed by muscular
      fibers interlacing, configuration that maintains residual regional pressure after
      myotomy; - in resting state, after myotomy, fundoplication exerts exclusively
      mechanical function, without increase of the lower esophageal sphincter pressure.

PMID- 8762683
TI  - [Esophageal histoplasmosis. A case report].
AB  - The authors report a case of a patient with complaint of progressive disphagia.
      Stenoses of lower third of esophagus was revealed by radiological and endoscopic
      examinations. Fungi were showed in biopsy of lesion, with demonstration of
      Histoplasm capsulate by tissue culture. Endoscopic dilatation was performed
      because especific medical treatment failed but esophageal rupture was observed.
      Partial esophagectomy was performed with symptoms remission.

PMID- 8762684
TI  - [Annular pancreas. Report of a case and review of the literature].
AB  - The authors present a case of newborn pre-term with birthweight of 2,250 g. There
      was polyhydramnios. On the first day she developed jaundice suggested upper
      intestinal obstruction. A plain radiograph of the abdomen confirmed the previous
      finding of obstruction of the duodenum, which showed a "double bubble" image with
      no other gas shadow in the rest of the abdomen. Contrast rodiologic examination
      of the abdomen confirmed total obstruction of the duodenum second portion. On the
      2nd day after birth, laparotomy revealed an annular pancreas. The reconstruction
      was made by a side-to-side proximal duodeno-jejuno-anastomosis. The postoperative
      course was uneventful. Barium radiography at one month postoperatively was good.

PMID- 8762685
TI  - Grynfelt hernia.
AB  - Lumbar hernias are very uncommon conditions. Less than 300 cases have been
      reported in the literature. They result from defects in the posterolateral
      abdominal wall. The authors report their experience with four lumbar hernias
      managed at the "Hospital das Clinicas da Faculdade de Medicina da Universidade de
      Sao Paulo" from 1973 to 1993. Age ranged from 54 to 63 years. Three were female,
      two had right hernias and two had left ones. All patients were treated
      surgically. Three were repaired by simple suture. The main complications were
      early recurrence (one case) and infections (one case). In one, a prosthetic mesh
      (polypropylene) was used to repair the defect, and the recovery was uneventful.
      Surgical treatment is always indicated in Grynfelt hernia. Approximation of the
      muscles by primary nonabsorbable suture, grafts or prosthesis are very adequate
      therapeutic options for lumbar hernias.

PMID- 8762686
TI  - [Gastrointestinal endocrine cells: brief history and main identification methods
      under light microscopy].
AB  - The gastrointestinal tract shows a wide spectrum of endocrine cells diffusely
      distributed along the mucosa, interspersed among the exocrine cells. These cells
      share several features such as the capacity to produce a series of peptides.
      Despite the development of digestive endocrinology, especially in the last decade
      and with respect to the biochemical knowledge and cellular localization of
      gastrointestinal regulatory peptides, their functional significance and their
      role in digestive phisiopathology remain partially unknown. This review
      represents a summary of the principal information about morphological and
      histochemical features, embryologic origin, historical data, methods of
      identification and types of endocrine cells, of gastrointestinal tract.

PMID- 8762687
TI  - [Coronary risk factors in children of young coronary artery disease patients].
AB  - PURPOSE: To determine whether children and adolescents, whose fathers have
      established coronary artery disease (CAD), have increased prevalence of coronary
      risk factors (RF). METHODS: The frequencies of abnormal values of lipid
      variables, glucose, blood pressure, obesity index (calculated through Newen
      Goldstein index), smoking and electrocardiographic alterations (ECG), were
      assessed in 280 descendents of young revascularized patients (< 55 years). The
      study population was divided in two groups according to age, respectively GA (2
      to 12 years) and GB (12 to 19 years). Eventual influences of age, gender, obesity
      and smoking on lipid variable were evaluated through variance analysis. RESULTS:
      Of the study population, 48.2% and 44.6% had total cholesterol (TC) and LDL-C
      respectively above the desirable values; 21.7% and 26.1% had values similar to
      adults under increased risk. Triglyceridemia (TG) > 200mg/dl was found in 1.4% of
      the sample and lower values of HDL-C in 16.8%. Overweight and obesity were
      observed in 13.1% and 20.0% of the patients and influenced TG levels in GB.
      Smoking occurred in 10.4%; hypertension in 3 cases and none had abnormal glucose
      levels or ECG. CONCLUSION: Healthy children of fathers with established CAD,
      exhibit a high frequency of altered lipid profile and increased body weight. The
      results suggest the need for early identification of RF in offspring of young CAD
      patients, thus emphasizing changes in risk profile and improving lifestyle.

PMID- 8762688
TI  - [Clinical and echocardiographic study of mitral valve in children with severe
      rheumatic carditis. Aspects of prolapse or rupture].
AB  - PURPOSE: To describe cases of rheumatic carditis with echocardiographic aspects
      of prolapse or rupture of mitral structures. METHODS: We described 16 cases of
      acute carditis (ages between 5-15 years). In 10 (group 1) there was aspect of
      mitral prolapse, in 6 (group 2) aspect of "flail". The measurements of anterior
      chordae and anuli were compared to the ones of 5 cases of chronic rheumatic fever
      with dilated left ventricle and aortic regurgitation (group 3) and to 20 normal
      children of same ages. The same measurements were repeated after treatment.
      RESULTS: The mean of the measurements in group 1 was; 26.48 +/- 11.46mm-anterior
      chordae; 32.13 +/- 7.35mm anuli; in the group 2 was respectively 29.63 +/- 4.57mm
      and 35.63 +/- 7 mm. In the group 3 anterior chordae was 34.52 +/- 6.8mm, anuli:
      34.8 +/- 4.61 mm. In the normal group, respectively was: 18.19 +/- 4.26mm and
      24.66 +/- 2.85mm. After corticosteroid many cases improved. In the statistical
      analyses, the measurements among patients of group 1 and 2 compared to normal
      children, the difference was significant but it was not compared to group 3.
      Comparing the measurements pre and post treatment the decrease was not
      significant. CONCLUSION: The acute carditis in these cases lead to significant
      elongation of anterior chordae and dilatation of anuli, but there was not a
      significant decrease after treatment.

PMID- 8762689
TI  - [Pathology of the heart in AIDS. Study of 73 consecutive necropsies].
AB  - PURPOSE: To study the incidence and the etiology of the cardiac lesions in AIDS
      patients. METHODS: The autopsy protocols and the filled slides of the heart from
      73 consecutive AIDS patients were reviewed. There were, at least, 2 slides of
      each heart stained by haematoxylin-eosin; when indicated, Ziehl-Nielsen, Gram and
      Gomori Grocott stains were used. RESULTS: No cause of death was assigned to the
      heart. There was involvement of the heart in 66 (90%) cases. Marked atrophy of
      cardiac fibers with or without lipomatosis was observed in 38 patients.
      Interstitial infiltrates of myocardium were present in 38 necropsies and in 13 of
      these cases a probable pathogen was demonstrated: cryptococcus neoforms in three
      cases and mycobacteria tuberculosis, atypical mycobacteria, toxoplasma' gondii,
      trypanosoma cruzi and cytomegalovirus in two cases each. Bacterial endocarditis
      was found in 4 autopsies and Kaposi sarcome in one. The pericardium was involved
      in 22 cases; in 12 there was only non specific mononuclear infiltration.
      CONCLUSION: Autopsy examination of the heart from AIDS patients revealed frequent
      pathologic involvement.

PMID- 8762690
TI  - [Bacterial infections in 100 patients submitted to heart transplantation].
AB  - PURPOSE: To evaluate clinical findings and etiology of bacterial infections
      diagnosed in 100 consecutive heart transplantations. METHODS: One hundred
      consecutive heart transplant patients were studied. Follow-up after heart
      transplantation varied from 3 to 90 (mean 25.38 +/- SD 25.97) months. Etiology of
      bacterial infection was established using the Centers for Disease Control
      criteria. RESULTS: Bacterial infection was the most common cause of infection
      after heart transplantation; diagnosis was difficult. Infection sites were skin,
      mucous, membranes, soft tissue, surgical scar, pericardial and pleural spaces,
      soft tissue around heart pacing devices, urinary tract; bacteremias and
      endocarditis were also found. All bacterial agents recovered were fully
      identified. CONCLUSION: Bacterial infections are the most common infections in
      the first month after heart transplantation. They are important and also common
      after the treatment of the rejection episodes. Rapid diagnosis and adequate
      treatment are essential to prevent morbidity and death.

PMID- 8762691
TI  - [Evaluation of a search for subjects in high risk for cardiovascular disease. An
      experience of the Heart Week--1993].
AB  - PURPOSE: To test the efficaccy of primary prevention in detecting a cluster of
      cardiovascular risk factors in a low income population and unaware individuals
      with hypertension, diabetes mellitus and hypercholesterolemia in the district of
      Butanta (Sao Paulo, Brazil). METHODS: We studied 156 people older than 40 years
      old, 126 (80.8%) female, mean age 53 years and observed their cardiovascular risk
      factors. RESULTS: The proportion of unaware hypertensive patients was of 46.4%
      among hypertensive women and 40.0% among hypertensive men; and about diabetes,
      the proportion of unawareness was 22.2% among diabetic women and 50.0% among
      diabetic men, although the total number of diabetics and of hypertensive men was
      very small. CONCLUSION: People with the following attributes: female, overweight,
      hypertensive and with glucose intolerance were those with more concern about
      health and prevention. In other hand, men and smokers were absent of those
      activities showing a low self-concern with health and disease.

PMID- 8762692
TI  - [A macromolecule capable of modifying CK-MB results and of inducing false acute
      myocardial infarction diagnosis].
AB  - PURPOSE: To evaluate the diagnostic value of CK-MB in acute myocardial
      infarction, to differentiate the relation between creatine phosphokinase (CPK),
      CK-MB and macro CK-BB (a macromolecule formed by an atypic CK-BB linked to an
      immunoglobulin) and to investigate the association of macro-BB with cancer.
      METHODS: We studied 105 patients: 47 with various tumors; 8 with acute myocardial
      infarction and one control group with 50 persons without cardiac or oncologyc
      diseases. The CK-MB, CPK and macro CK-BB were measured in the serum of all
      patients and of the control group. RESULTS: Among patients with cancer, 12
      (25.6%) showed positive serum macro CK-MB. Two of them (16.6%) showed concomitant
      increase in CK-MB. All patients with increased serum macro CK-MB had malignant
      tumors. CONCLUSION: The CK-MB is a reliable test for the myocardial infarction,
      however, when this isozyme is increased in the presence of normal CPK value, it
      must be questioned the presence of macro CK-BB to avoid false positive results.
      The presence of macro CK-BB could be relationed with malignant disease, specially
      with carcinoma of the prostate.

PMID- 8762693
TI  - [Complete heart block after percutaneous mitral valvotomy with Inoue balloon].
AB  - We report a permanent complete heart block, in a 27 year-old female patient,
      developed during mitral percutaneous valvotomy using a single inflation of the
      Inoue balloon catheter. After one month, even using corticoids, a Mobitz II
      second-degree atrioventricular block persisted, the patient became symptomatic to
      moderate efforts and a cardiac pacemaker was implanted.

PMID- 8762694
TI  - -Rate-responsive pacemaker with an unexpected chronotropic response-.
AB  - The pacemaker with rate-responsiveness was a great advance in cardiac
      stimulation, however, the choice of the best biosensor is still object of
      research. A 35 year-old woman with a responsive pacemaker implanted due to a
      complete heart block after interventricular septal defect surgical correction was
      admitted. The pacemaker showed improper cronothropic response with high frequency
      due to biosensing malfunction. Malfunction related to muscle stimulation in the
      generator pocket and a high response rate. A palliative procedure was made until
      the end of pregnancy, by reducing the sensitivity of biosensing.

PMID- 8762695
TI  - [Coronary fistula associated with severe pulmonary stenosis and cianosis].
AB  - A 17 year old male adolescent was admitted to the hospital due to dyspnea and
      cyanosis, since the age of 6 years. On physical examination, it was found a
      continuous murmur over the left esternal border at the 4th and 5th intercostal
      spaces suggesting a coronary fistula. A color-echocardiogram associated with an
      angiography confirmed the diagnosis of coronary fistula and severe pulmonary
      stenosis. The functional consequence was a right to left shunt with cyanosis. A
      surgical repair was performed with closure of the fistula at the point where it
      drained into the right ventricle plus a pulmonary commissurotomy. The patient had
      an uneventful recovery.

PMID- 8762696
TI  - [Anatomo-clinical correlation. Case 1/96. Instituto do Coracao do Hospital das
      Clinicas FMUSP].

PMID- 8762697
TI  - [Devalued consultation. Cause or consequence of the abuse in the use of medical
      technology?].

PMID- 8762698
TI  - [Coronary microvascular changes in Chagas' disease].

PMID- 8762700
TI  - [Psychiatry and its future].

PMID- 8762699
TI  - [Brazilian multicenter study of sotalol effectiveness in ventricular
      arrhythmias].
AB  - PURPOSE: To evaluate the effects of sotalol in patients with nonsustained
      ventricular tachyarrhythmia (NSVT). METHODS: Ninety patients were enrolled.
      Patients were submitted to a double-blind crossover randomized study (placebo x
      320 ms/po/d/sotalol; 4 weeks, after a wash-out control period. Holter recordings
      were performed in control (Ct), placebo (Pb) and drug (Dg) periods. Eligible
      patients had > 50/h isolated ventricular premature beats (VPB), in control, with
      or without pairs (P) or nonsustained VT (NSVT; > 3 beats, > 100bpm). Drug
      efficacy criteria were; > or = 75% reduction in isolated VPB, reduction > or =
      90% of P and NSVT. The effects of the Dg were evaluated in the global population,
      in patients with Chagas' disease, idiopathic arrhythmias and
      ischemic/hypertensive patients. RESULTS: Differences between control and placebo
      were NS. Isolated VPB; Dg was effective in 42% (38/90 patients) with a mean of Pb
      and Dg respectively of 11,770 +/- 13,818 and 1,043 +/- 1,554 (p < 0.001). Pairs:
      drug was effective in 48% (32/67 patients) with a mean of Pb and Dg respectively
      of 439 +/- 586 and 27 +/- 52 (p < 0.001). NSVT: drug effectiveness was 53% (19/36
      patients) with a mean of Pb and Dg respectively of 445 +/- 1,148 and 2.5 +/- 5.8
      (p < 0.102). In patients with Chagas' disease, the reduction in VPB was 33%
      (13/39 patients), in pairs was 42+ (14/34) and in NSVT was 64% (12/22). In
      idiopathic patients the reduction of VPB was 53% (17/32 patients), in pairs was
      50% (10/20) and in NSVT was 36% (4/11). In ischemic and hypertensive patients the
      reduction of VPB was 47% (7/15 patients) and 73% in pairs (8/11). CONCLUSION: In
      the present study, sotalol was effective in the control of nonsustained
      ventricular tachyarrhythmia, with minimal side-effects.

PMID- 8762701
TI  - [Clinical dimensions of contemporary cultural psychiatry].
AB  - In spite of the difficulties to define the term "culture" there is agreement with
      regards to its profound influence in the contemporary social environment of which
      medicine and psychiatry are important components. Cultural psychiatry studies
      psychopathology inasmuch as it reflects and it is subjected to the influence of
      cultural factors within the biopsychosocial context. Its contemporary clinical
      dimensions cover five fundamental areas: culture as an interpretive/explanatory
      instrument of human behavior; as a pathogenic/pathoplastic agent; as a
      diagnostic/nosological factor; as a therapeutic/protective element, and as a tool
      for management and service delivery. This paper examines the conceptual nature of
      each of these roles and presents pertinent examples from the clinical literature,
      away from theoretical lucubrations. The cultural legacy of each and every patient
      seen by the psychiatrist or any other mental health professional demands serious
      studies and effective actions at all levels.

PMID- 8762702
TI  - [Classification in actual psychiatry].
AB  - The importance of diagnosis in psychiatry is relevant for therapeutic, research
      and public health questions. During the '70s, operational criteria improved ways
      for developing reliability and the basis of validity of psychiatric diagnosis.
      However, the possibility of a common language in psychiatry has been in doubt
      because of the proliferation of operational systems. There are also reductionist
      trends that could be dangerous for psychopathology and pedagogy.

PMID- 8762703
TI  - [Social drinking and adolescent parties].
AB  - A study carried out with 250 young students showed how much alcohol is socially
      accepted during young people parties. Significant differences were observed
      according to kind of alcoholic beverage, specially greater alcohol consumption of
      those of less alcoholic graduation.

PMID- 8762704
TI  - [Young men and psychoactive substances].
AB  - This study compares prevalence rates of psychoactive substances use in two
      samples of young men who were called to the Military Service Medical Examination,
      in Buenos Aires city, in two different periods of time: in 1992, a thousand nine
      hundred eighty men were included, and in 1994, a thousand four hundred eighty men
      answered the questionnaire. Same methodological procedures were applied in both
      periods. Marihuana consumption level showed no changes; little decrease were
      observed in cocaine declared consumption; alcohol abuse level also declined.
      Nevertheless, more than 3 of each ten young men recognized an alcoholic ingestion
      of more of 100 cc of absolute alcohol during the past 30 days before in both
      studies. Relations between use of legal and illegal psychoactive substances are
      explored in the 1994 sample.

PMID- 8762705
TI  - [Value priorities and drug addiction].
AB  - To explore addicted and non-addicted differences on values, the Schwartz's values
      scale was administered to 194-male/female, addicted/non-addicted university
      students sample. Addicted group was composed by students using drugs at least
      once a week and non-addicted group by subjects who never used illegal drugs.
      Anova 2X2 revealed a main effect of drug use variable on several motivational
      value types: hedonism, stimulation, self-determination, universalism and
      conformity. Addicted subjects scored higher on the four first types and non
      addicted on the last. Several sex X addiction interaction were also significant.
      The transgression hypothesis was used to explain the results.

PMID- 8762706
TI  - [Socioeconomic reality: the context in which vocational and professional guidance
      have to deal with].
AB  - In this work we describe and analyze today's Latin American occupational reality,
      according to the world economical context we live in. We mention up-to-date data
      about employment and unemployment rates, from different countries of Latin
      America, Europe, and also from Japan. Besides that we have taken into account the
      technological development and the demographic growth, as essential variables in
      order to understand the labor phenomenon and its possible prospect, as well as
      the psychosociological consequences or unemployment. We also analyze the future
      of some professions. We think that all this information gathered from different
      sources, is essential to the professional who has to guide teen-agers at the time
      of the Ocupational-Vocational election. This is also necessary to all those who
      deal with Professional Guidance and with the Planning of Careers that have
      already been chosen.

PMID- 8762707
TI  - [Premenstrual symptomatology in rural and urban zones].
AB  - The objective of this study was to stablish the prevalence and severity of
      premenstrual symptoms in mexican women who live in a rural zone (n = 50) and in
      other group who live in a urban zone (n = 50). The Menstrual Distress
      Questionnaire (MDQ) was applied during the premenstrual and postmenstrual phases
      of one menstrual cycle. The 97% of the sample presented at least one premenstrual
      physical symptom, and the 95% of the women presented one psychological-behavioral
      symptom. There were not differences according with the severity of the physical
      symptoms between both groups of women. However, women in the urban zone reported
      more severe psychological-behavioral symptoms then the ones who live in the rural
      zone.

PMID- 8762708
TI  - [Latin American psychology: a two-way start].
AB  - Two main trends can be found in psychological historiography, both streaming from
      discipline: on one hand the Central-European trend, phenomenological and dealing
      with inner life, and on the other, the Anglo-American trend, empirical and
      pragmatic. Latin America has reflected this cultural phenomenon in an extreme
      shadeless manner which had a clear influence in undergraduate schools. Modern
      psychology tendencies, however, don't allow the continuity of such a state of
      matters, and this has begun to reflect in the academic atmosphere of the region.

PMID- 8762709
TI  - [Electroconvulsive therapy: indications and improvement].
AB  - Electroconvulsive therapy (ECT) is considered today as an affective and safe
      treatment, although some indications for its use are based more in the
      professional consensus than in the clinical research. As with any treatment, both
      therapeutic outcome and adverse effects can be expected to vary considerably
      across patients. It is incumbent upon the practitioner to be aware of factors
      that serve to influence the benefits and risks associated with this treatment
      modality. The author reviews current indications, and those factors that may be
      useful in response prediction, as well as, technical modifications of the ECT
      procedure itself.

PMID- 8762710
TI  - [Psycholexicology: some approaches].

PMID- 8762711
TI  - [The opiates-opioids binominal apropos of recent appearance of DSM-IV in
      Spanish].

PMID- 8762712
TI  - Images of cone photoreceptors in the living human eye.
AB  - Though the photoreceptor mosaic has been imaged through the intact optics of the
      eyes of several species, it has not been clear whether individual photoreceptors
      can be resolved in the living human eye. We have constructed a high-resolution
      fundus camera and have resolved cones with a spacing as small as 3.5 microns in
      single images of the fundus. The high contrast of these images implies that
      almost all the light returning from the retina at this wavelength (555 nm) has
      passed through the apertures of foveal cones. The average power spectra of our
      retinal images show that it is possible to recover spatial frequencies as high as
      150 c/deg in eyes with normal optical quality, a conclusion that was confirmed
      with estimates of the optical quality of these eyes obtained with a Hartmann
      Shack wavefront sensor. These results emphasize the superiority of the eye's
      optics over the spatial sampling limits of the retina when the eye's optical
      quality is optimized. They also show that it would be possible to routinely
      resolve retinal structures as small as photoreceptors in the normal living eye if
      its aberrations could be corrected.

PMID- 8762713
TI  - Monoclonal antibody C38 recognizes retinal ganglion cells in cats and rats.
AB  - We developed monoclonal antibody C38 which specifically recognizes retinal
      ganglion cells (RGCs) in flatmount preparations of cat and rat retinas. We first
      induced immunological tolerance in Balb/c mice against axotomized rat retinas
      which lack most of the RGCs. Then the mice were immunized with intact rat retinas
      to produce antibodies against RGCs. Monoclonal antibody C38 appeared to be
      specific for cat RGCs based on immunoreactivities seen in flatmounts and vertical
      sections of the retina. In rats, we verified that over 90% of retrogradely
      labeled RGCs were immunoreactive for C38 antibody. In axotomized rat retinas,
      surviving RGCs were labeled with C38 without erroneous labeling of glial cells.
      The antigen that C38 recognized was 24 kDa in molecular weight and found in
      cerebrum, cerebellum, and spinal cord as well as retina. It is suggested that
      monoclonal antibody C38 is a useful label for RGCs.

PMID- 8762714
TI  - [Ca2+]i regulation by glutamate receptor agonists in cultured chick retina cells.
AB  - The effect of glutamate receptor agonists on the intracellular free calcium
      concentration ([Ca2+]i), measured with Indo-1, was studied in populations of
      cultured chick embryonic retina cells. The agonists of the ionotropic glutamate
      receptors, N-methyl-D-aspartate (NMDA), kainate, and alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) increased the [Ca2+]i through a composite
      effect, comprising Ca2+ permeating the receptor-associated channels, and Ca2+
      entering through voltage-gated Ca2+ channels. Furthermore, the [Ca2+]i responses
      to NMDA and AMPA also involved Ca2+ release from intracellular stores, which
      could not be mobilized by stimulation of the metabotropic receptor.

PMID- 8762715
TI  - Off-axis optical quality and retinal sampling in the human eye.
AB  - Using the double pass procedure, Navarro et al. (1993; Journal of the Optical
      Society of America A, 10, 201-212) measured the monochromatic modulation transfer
      function (MTF) of the human eye as a function of retinal eccentricity. They chose
      conditions as similar as possible to those encountered in natural viewing. We
      report new measurements obtained with conditions chosen instead to optimize
      retinal image quality: we paralyzed accommodation, used a 3 mm pupil, and
      corrected defocus and oblique astigmatism at each retinal location. MTFs were
      estimated at the tangential focus, circle of least confusion, and sagittal focus
      produced by oblique astigmatism. Though optical blur is well-known to have little
      effect on peripheral visual acuity, it can nonetheless substantially reduce
      aliasing by receptoral and post-receptoral spatial sampling.

PMID- 8762716
TI  - A model for inhibitory lateral interaction effects in perceived contrast.
AB  - The apparent contrast of a centrally viewed Gabor target patch was measured by
      contrast matching in the presence of Gabor flanking patches positioned on a ring
      of radius r from the center of the target patch. Central patch apparent contrast
      was determined as a function of the number of flanking patches, the radius r of
      the ring, and the contrasts of both central and flanking patches. The apparent
      contrast of the central patch was reduced by the presence of the flanking patches
      for all experimental conditions. A two layer non-linear model for contrast
      perception accounts quite well for the data. The first layer performs a power
      function transformation on the contrast signals from the patches. The second
      layer takes the outputs from the first layer and divides them by one plus the
      square root of spatially weighted responses of nearby first layer mechanisms.

PMID- 8762717
TI  - Differences between stereopsis, interocular correlation and binocularity.
AB  - In normal human subjects, evoked potentials in response to depth reversing two
      color dynamic random-dot stereograms disappeared or were greatly reduced at
      equiluminance, whereas responses to shifts between patterns that were correlated
      and anticorrelated (for the two eyes) were, for most subjects, actually larger at
      equiluminance than at non-equiluminance. Responses were only slightly diminished
      at equiluminance to similar texture-shifting patterns that were identical to the
      two eyes. These results suggest that a significant fraction of cells with input
      from both eyes can respond to correlation/anticorrelation shifts, yet are not
      involved in stereopsis. Also, binocular rivalry may gate the responses of these
      binocular-nonstereoscopic units.

PMID- 8762718
TI  - The relative efficacy of cues for two-dimensional shape perception.
AB  - The visual system uses a variety of cues for form perception, including motion,
      color, binocular disparity, texture, and luminance. Physiological evidence
      suggests that these cues are processed by different neural mechanisms. Do the
      cues processed by some mechanisms convey any advantage for form perception when
      compared to cues processed by another? In response to this question we assessed
      the relative efficiency of several cues in conveying two-dimensional form from
      background noise. For the sake of comparison, every cue type used the same
      experimental design and stimulus set. Our results confirm that movement is one of
      the most efficient cues for shape perception. Also, a simple transient cue (an
      instantaneous flashing on or off) is equally useful. In comparison, local dot
      density (a type of texture cue) was the least efficient. The efficiencies of most
      other cues, such as color, stereopsis, and relative movement in noise, were
      conspicuously similar.

PMID- 8762720
TI  - Does the human visual system implement an ideal observer theory of slant from
      texture?
AB  - Texture information about surface shape can be decomposed into three
      constituents: compression, density and scaling. Blake, Bulthoff and Sheinberg's
      (1993, Vision Research, 33, 1723-1737) Ideal Observer theory of slant from
      texture predicts that the relative contribution of compression and density to the
      percept of planar surface slant should vary with field of view (FOV). The
      contribution of compression and density should both increase as FOV increases but
      statistical analysis shows that the reliability, and hence the expected
      contribution, of density increases at a greater rate than compression with
      increasing FOV. Specific predictions are that at FOV < 20 deg compression should
      be more effective than density, at FOV approximately 20 deg, compression and
      density should be equally effective, and at FOV > 20 deg, compression should be
      less effective than density. These predictions were tested by pitting these
      components of texture against one another. The method used was similar to that
      described in Frisby and Buckley [1992 In Orban, G. & Nagel H.-H. (Eds) Artificial
      and biological visual systems. Berlin: Springer]: observers judged binocularly
      the slant of a large table on to which was projected a texture created using
      computer graphics to contain various texture component cues to slant. The size of
      the projected texture patch determined the FOV which was by this means set to
      either 10, 20 or 30 deg. It was found that compression was the dominant cue
      irrespective of FOV, even if it was perturbed by noise. Possible reasons for this
      divergence of human observers from predictions of the Ideal Observer theory of
      slant from texture are discussed.

PMID- 8762719
TI  - Sensitivity to spatial phase at equiluminance.
AB  - We have measured sensitivity for discriminating the spatial phase of multi
      harmonic and two-harmonic patterns modulated either in luminance or in
      chromaticity (red-green). The multi-harmonic patterns were either highpass
      squarewaves, lines or ramps. For all patterns, contrast thresholds for
      discriminating 0 from 180 deg phase were similar to those for discriminating -90
      from 90 deg, for luminance or chromatic modulation (or both). For all types of
      multi-harmonic patterns, the ratio of contrast thresholds for the phase
      discrimination to that for pattern detection was the same for luminance and
      chromatic modulation, and for combinations of both. Similarly, phase thresholds,
      the minimum detectable differences in phase (about a mean 0 deg), were the same
      for chromatic and luminance patterns, provided that contrast was scaled to equate
      detection thresholds of the patterns. Similar results were observed for simple
      three-harmonic patterns (f + 2f + 3f), and for (f + 2f) two-harmonic patterns.
      Strangely, however, two-harmonic patterns of f + 3f (first two terms of square
      wave) of moderate to high spatial frequency did show a two-fold advantage for
      luminance over colour, as Troscianko and Harris (1988) have previously reported
      (Vision Research, 28, 1041-1049), possibly because the two harmonics have a
      greater separation in frequency. However, for most classes of patterns,
      sensitivity for spatial phase is as good for chromatic as for luminance
      modulation, suggesting that similar sorts of mechanisms operate under these two
      conditions.

PMID- 8762721
TI  - Direction repulsion between components in motion transparency.
AB  - We measured the perceived direction of one motion component as a function of the
      contrast and speed of a second component for three pattern classes: plaids with
      two different spatial frequency components, multi-aperture patterns, and contrast
      modulated (CM) patterns. The components were moving at +/- 63.4 or +/- 71.6 deg
      to the vertical, angles where motion transparency always occurred under our
      conditions. For multi-aperture and CM patterns on a single spatial scale, the
      components were perceived to deviate from the component motion directions by up
      to 20 deg at high contrasts or high speeds of the second component. However, for
      plaids with components on different spatial scales, the test components were
      perceived moving in the component directions regardless of the contrast or the
      speed of the second component. Our data show that this direction repulsion
      between components occurs within a single spatial scale but not between widely
      separated spatial scales. This implies that two different mechanisms are involved
      in motion transparency.

PMID- 8762722
TI  - Effect of exposure duration on spatial uncertainty in normal and amblyopic eyes.
AB  - Previous studies have found that the spatial uncertainty of amblyopes is
      critically dependent on temporal factors. These studies claim that the spatial
      uncertainty is much greater at short exposure durations. We have reassessed the
      effect of exposure duration on the spatial uncertainty of normal and amblyopic
      eyes using a task in which we can compensate for the loss in contrast sensitivity
      which inevitably occurs as exposure duration is shortened. Our task involved a
      three-element alignment task, where each of the elements were spatial Gabors at
      two different separations. We ensured that our stimuli were always displayed at a
      fixed ratio above contrast detection thresholds at each exposure duration. Our
      results show that for normal subjects, for well separated equivisible stimuli,
      there is only a weak effect of exposure duration. A similar dependence is found
      for the dominant and amblyopic eyes of a group of strabismic amblyopes. Dominant
      eyes of strabismic amblyopes show increased spatial uncertainty compared with
      normal subjects. Amblyopic eyes of strabismic amblyopes show increased spatial
      uncertainty compared with their dominant fellow eye which is invariant with
      exposure duration. Some subjects show a larger positional deficit at short
      durations when the stimuli are almost abutting.

PMID- 8762723
TI  - Adaptation of vertical eye alignment in relation to head tilt.
AB  - Binocular visual feedback is used to continually calibrate binocular eye
      alignment so that the retinal images of the two eyes remain in correspondence.
      Past experiments have shown that vertical eye alignment (measured as vertical
      phoria) can be altered by training to disparities that vary as a function of
      orbital eye position. The present experiments demonstrate that vertical eye
      alignment can also be trained to differ with head position when eye position
      (with respect to the orbit) is held constant. Changes in head position were about
      either an earth-vertical or earth-horizontal axis to distinguish otolith-ocular
      related adaptation from cervical-ocular related adaptation. Changes in head
      position were implemented by either by rotating the whole body (WB) or by
      rotating the head with the body stationary (HO). Following training, adaptation
      of eye alignment was observed in all cases of rotation about an earth-horizontal
      axis and for HO pitch rotations about an earth-vertical axis. The results
      illustrate the ability of the oculomotor system to compensate for imbalances in
      otolith-ocular pathways.

PMID- 8762724
TI  - Infant peripheral vision: the development of monocular visual acuity in the first
      3 months of postnatal life.
AB  - Quantitative data on the early morphological development of the human retina show
      that the peripheral region is relatively more mature than the central region.
      These results have stimulated researchers to compare the development of visual
      functions in the central and peripheral regions of the visual field. Here, we
      used preferential looking to evaluate 1-, 2- and 3-month-old infants' central and
      peripheral (10 degrees and 30 degrees) monocular visual acuity. There were three
      findings: (i) both central and peripheral acuities were poor at 1 month, improved
      over the age range tested, but were still about 3 octaves worse than adults'
      acuity; (ii) at all ages monocular acuity decreased with increasing eccentricity;
      (iii) 2- and 3-month-olds showed higher acuity for gratings in the temporal than
      in the nasal visual field at 30 degrees. The implications of these results for
      issues in visual development are discussed.

PMID- 8762725
TI  - 11 beta-Hydroxysteroid dehydrogenase: implications for clinical medicine.

PMID- 8762726
TI  - Wasting in the acquired immune deficiency syndrome is associated with multiple
      defects in the serum insulin-like growth factor system.
AB  - OBJECTIVE: The aim of this investigation was to characterize the GH-IGF axis of
      patients with AIDS associated wasting. A special emphasis was placed on
      determining whether IGF binding proteins (IGFBPs) of patients who have lost more
      than 10% of their ideal body mass are structurally different from the IGFBPs of
      patients with no weight loss. DESIGN AND PATIENTS: A cross-sectional study of 11
      AIDS patients was performed to determine whether the IGF system is abnormal in
      AIDS patients with wasting. Seven additional AIDS patients were followed
      longitudinally to determine whether AIDS patients experience long-term changes to
      their IGF system. MEASUREMENTS: Serum levels of GH and IGF-I were measured by
      radioimmunoassay, IGF-II was measured by radioreceptor assay, and IGFBP-1 was
      measured by an enzyme linked immunoassay. IGFBP-3 and IGFBP-3 protease activity
      were measured by ligand blotting and a BP-3 protease assay, respectively. IGFBP-3
      ternary complex formation and IGFBP-1 phosphovariants were analysed by non
      denaturing PAGE. RESULTS: AIDS patients who had lost more than 10% of their ideal
      body mass demonstrated a 55% reduction in serum IGF-I (81 vs 179 micrograms/l)
      and a 70% reduction in IGF-II (226 vs 776 micrograms/l), compared to healthy HIV
      negative subjects. IGF-I levels were depressed, in some patients, despite high
      serum levels of GH. AIDS patients who had lost more than 10% of their ideal body
      mass had low levels of IGFBP-3 and a reduced ability to form the IGFBP-3 ternary
      complex. The IGFBP-3 ternary complex could be restored only upon addition of pure
      IGFBP-3 and acid labile subunit to serum. Serum IGFBP-1 was increased more than
      threefold compared to control subjects (90 vs 24 micrograms/l). IGFBP-1 was
      present as a free phosphoprotein in AIDS patients with low levels of IGF-I and in
      a bound form when serum IGF-I levels were normal. Changes in the GH-IGF axis were
      sustained for up to 25 months in AIDS patients with wasting. CONCLUSIONS: AIDS
      wasting is associated with a GH resistant state that results in low levels of
      serum IGF-I, IGF-II and IGFBP-3, elevated levels of phosphorylated IGFBP-1, and a
      reduced ability to form the IGFBP-3 ternary complex.

PMID- 8762727
TI  - Serum concentrations of free and total insulin-like growth factor-I, IGF binding
      proteins -1 and -3 and IGFBP-3 protease activity in boys with normal or
      precocious puberty.
AB  - OBJECTIVE: Circulating IGF-I and IGF binding protein-3 (IGFBP-3) levels both
      increase in puberty where growth velocity is high. The amount of free IGF-I is
      dependent on the IGF-I level and on the concentrations of the specific IGFBPs.
      Furthermore, IGFBP-3 proteolysis regulates the bioavailability of IGF-I. However,
      the concentration of free IGF-I and possible IGFBP-3 proteolytic activity in
      puberty has not previously been studied. SUBJECTS AND MEASUREMENTS: We
      investigated serum levels of easily dissociable IGF-I concentrations and
      ultrafiltrated free IGF-I levels by specific assays in 60 healthy boys and in 5
      boys with precocious puberty before and during GnRH agonist treatment. In
      addition, total serum IGF-I, IGFBP-1 and IGFBP-3 levels as well as IGFBP-3
      protease activity were determined. RESULTS: Free (dissociable and ultrafiltrated)
      IGF-I concentrations were significantly higher in pubertal boys than in
      prepubertal children and correlated significantly with the molar ratio between
      IGF-I and IGFBP-3 (r = 0.69, P < 0.0001 and r = 0.54, P = 0.0008, respectively)
      and inversely with IGFBP-1 (r = -0.47, P < 0.0001 and r = -0.43, P = 0.0003,
      respectively). Multiple regression analysis suggested that IGFBP-3 level, and not
      IGFBP-1, was the major determinant of the free IGF-I serum level in normal boys.
      Free IGF-I levels were elevated in boys with precocious puberty and decreased
      during GnRH treatment. IGFBP-3 proteolysis was constant throughout puberty (mean
      20%). CONCLUSIONS: We conclude that easily dissociable and ultrafiltrated free
      IGF-I serum levels are increased in boys with normal and precocious puberty and
      suggest that the increased free IGF-I serum concentration in puberty primarily
      reflects changes in total concentrations of IGF-I and IGFBPs secondary to
      increased GH secretion, but that it is not influenced by changes in IGFBP-3
      proteolysis.

PMID- 8762728
TI  - Regulation of the acid-labile subunit of the insulin-like growth factor ternary
      complex in patients with insulin-dependent diabetes mellitus and severe burns.
AB  - OBJECTIVE: Little information is available regarding the regulation of serum acid
      labile subunit (ALS) in human disease. We have studied alterations in serum ALS
      of the insulin-like growth factor (IGF) ternary complex in children with
      untreated insulin-dependent diabetes mellitus (IDDM) and subjects with severe
      burns before and after insulin therapy. In addition, we have investigated the
      effect of insulin plus GH on serum ALS in burn patients. DESIGN: Serum samples
      were obtained from children with newly diagnosed and untreated IDDM before the
      initiation of insulin therapy and 1 month thereafter. Serum samples were also
      obtained from adult patients with severe burns who were on a continuous infusion
      of a carbohydrate-rich enteral diet via nasogastric and duodenal catheters under
      basal conditions, after a 1-week period of continuous insulin infusion, and after
      an additional week of insulin plus recombinant GH. PATIENTS: Twenty children and
      adolescents with untreated IDDM, aged 1.2-16 years, and 6 young adult patients
      with severe burns aged 17-28 years were studied longitudinally. Control sera were
      obtained from age, sex and pubertal status matched subjects (for children with
      IDDM) and from fed healthy adults. MEASUREMENTS: Serum insulin, GH, cortisol and
      IGF-I were measured by radioimmunoassay, and serum ALS levels were assessed by
      Western immunoblot before and after treatment periods. RESULTS: Serum ALS levels
      were lower in untreated children with IDDM (69 +/- 6% of control children).
      Insulin therapy significantly increased serum ALS (79 +/- 5%, P < 0.05) in these
      children. Patients with severe burns also had lower serum ALS levels (79 +/- 10%
      of control adults). After one week of insulin therapy serum ALS levels increased
      to 90 +/- 15% of control values (P < 0.05). Addition of GH to insulin therapy for
      another week did not significantly further increase serum ALS levels (95 +/-
      27%). Serum IGF-I concentrations increased nearly 2.5-fold in diabetic subjects
      and fourfold in burn subjects at the end of the study periods. There were no
      proteolytic fragments of ALS in the sera studied. The deglycosylation pattern of
      ALS did not differ between diabetic and control sera. CONCLUSION: Serum ALS
      levels were diminished in children with untreated IDDM and were partially
      restored after the initiation of insulin therapy. Serum ALS levels were also
      diminished in patients with severe burn injury and restored by insulin treatment.
      Addition of GH to insulin therapy did not significantly increase serum ALS levels
      over levels obtained during insulin therapy alone. These decreases in serum ALS
      were smaller than the decrease in serum IGF-I concentrations in both conditions,
      suggesting that IGF-I is the limiting factor for the ternary complex formation in
      the catabolic states. Insulin may regulate circulating ALS levels in catabolic
      states and helps to restore the IGF system.

PMID- 8762729
TI  - Decreased plasma and extracellular volume in growth hormone deficient adults and
      the acute and prolonged effects of GH administration: a controlled experimental
      study.
AB  - OBJECTIVE: There are few data on the endocrine mechanisms underlying the body
      fluid changes in GH deficiency and their subsequent alteration following GH
      replacement. We have therefore investigated the time effects of GH on body fluid
      distribution and fluid regulating hormones in GH deficient adults. DESIGN: The
      patients underwent in random order four study periods: (1) saline, a 42-hour
      infusion following 3 weeks without GH, (2) acute GH, a 42-hour GH infusion
      following 3 weeks without GH, (3) 3 days GH, a 42-hour GH infusion preceded by 3
      weeks without GH and 3 days pretreatment with subcutaneous GH injections, (4) 3
      weeks GH, a 42-hour GH infusion after at least 3 weeks GH therapy. SUBJECTS:
      Seven GH deficient adult males and 8 healthy control subjects. MEASUREMENTS:
      During each infusion period 24-hour blood pressure was recorded, bioimpedance was
      repeatedly measured and blood samples were obtained every 6 hours. After 41 hours
      extracellular and plasma volumes were determined isotopically. Extracellular
      volume, plasma volume and bioimpedance were measured in the control group.
      RESULTS: GH increased extracellular volume (saline 16.45 +/- 0.79 vs acute GH
      16.83 +/- 0.87; vs 3 days GH 17.58 +/- 0.71; vs 3 weeks GH 17.92 +/- 0.88 l, P =
      0.01). After 3 weeks of GH, extracellular volumes in the patients and in the
      control group were identical (control 17.94 +/- 0.32). Plasma volume was
      increased only after 3 weeks GH treatment (saline 2.93 +/- 0.16 vs acute GH 3.04
      +/- 0.22; vs 3 days GH 3.06 +/- 0.07; vs 3 weeks GH 3.37 +/- 0.18 l, P = 0.03),
      and was decreased compared to the control group (control 3.56 +/- 0.03 l, P <
      0.01). Bioimpedance decreased significantly in all treatment periods and was
      significantly increased compared to the control group. Plasma renin increased
      during GH administration (saline 16.2 +/- 1.9 vs acute 19.0 +/- 1.9; vs 3 days GH
      30.8 +/- 3.0; vs 3 weeks GH 27.0 +/- 3.0 mU/l, P = 0.03), whereas aldosterone and
      atrial natriuretic factor (ANF) levels remained unaffected by GH. GH caused an
      increase in systolic blood pressure (BP) and heart rate, whereas diastolic BP
      remained unaffected. CONCLUSIONS: The present data show that GH deficiency is
      associated with decreased plasma volume and extracellular volume. GH exposure
      acutely increases extracellular volume, whereas substitution for a longer time
      was required to normalize both extracellular and plasma volumes. Renin seems to
      be involved in these fluid volume regulating effects of GH.

PMID- 8762730
TI  - Specific stimulation of brain serotonin mediated neurotransmission by
      dexfenfluramine does not restore growth hormone responsiveness in obese women.
AB  - OBJECTIVE: Growth hormone release in response to all known stimuli of GH
      secretion is blunted in obese subjects. Several studies, using d,l-fenfluramine
      (d,l-FF) as a serotoninergic tool, suggest that brain serotonin plays a role in
      the pathogenesis of this phenomenon. However, the effect of d,l-FF appears to be
      dependent on the stimulus used to induce GH release. Furthermore, d,l-FF has
      catecholamingergic properties apart from its capacity to stimulate serotonin
      release and to block its re-uptake. In this study, we investigated whether
      subchronic treatment with the highly selective serotoninergic drug
      dexfenfluramine (d-FF) affects the GH response to galanin or GHRH in obese
      subjects. DESIGN: The study had a randomized, cross-over, placebo controlled
      design. d-FF was administered in a dose of 15 mg twice daily during 6 days. On
      days 5 and 6 of treatment (with either d-FF or placebo) an i.v. bolus injection
      of 100 micrograms hGHRH(1-44) or a continuous infusion of p-galanin (40
      pmol/kg/min over 40 minutes) were administered in randomized order. All tests
      were performed in the follicular phase of two consecutive menstrual cycles.
      PATIENTS: Eight obese women (body mass index (BMI) 34.5 +/- 3.6 kg/m2); 7 normal
      weight (BMI 21.9 +/- 1.9 kg/m2) age-matched control women. All women had a
      regular menstrual cycle. None used oral contraceptive drugs. MEASUREMENTS: GH
      response to either stimulus was measured both during treatment with d-FF and
      during treatment with placebo. RESULTS: The GH response to galanin and the
      response to GHRH were significantly smaller in obese subjects. d-FF significantly
      reduced the galanin induced GH secretion in obese subjects, but not in normal
      weight controls. It did not significantly affect GH release in response to GHRH
      in either group. CONCLUSION: This study confirms that GH secretion in response to
      stimuli with varying mechanisms of action is blunted in obese subjects. A
      decrease of central serotonin mediated neurotransmission does not appear to play
      a role in the pathogenesis of this phenomenon.

PMID- 8762731
TI  - Growth hormone responses to growth hormone-releasing hormone and clonidine in
      patients with type I diabetes and in normal controls: effect of age, body mass
      index and sex.
AB  - OBJECTIVE: Increased plasma concentrations of GH and increased GH responses to
      provocative stimuli are reported in patients with poorly controlled type I
      diabetes and are suggested to be related to complications. Our aim was to
      investigate GH concentrations in moderately controlled patients. PATIENTS AND
      MEASUREMENTS: We have investigated IGF-I concentrations and fasting GH
      concentrations and the response to 1 microgram/kg body weight GH-releasing
      hormone (GHRH) intravenously and/or to 150 micrograms clonidine intravenously in
      77 moderately controlled patients with type I diabetes and in 46 healthy
      controls. RESULTS: Median HbA1c in the patients was 8.5% (upper level of normal
      6.3%). Fasting GH and GH concentrations after the administration of GHRH were not
      significantly different in patients with type I diabetes compared with normal
      controls. Fasting and stimulated GH concentrations after the administration of
      clonidine were significantly higher in the patients, but this could be explained
      by their lower age and body mass index compared with controls. In controls but
      not in patients there was a negative correlation between GH and glucose
      concentrations. IGF-I was significantly lower in patients with diabetes than in
      controls, even after correction for age, body mass index and sex. CONCLUSIONS:
      Patients with moderately controlled type I diabetes mellitus have normal baseline
      and stimulated GH concentrations after the administration of GHRH or clonidine
      compared with healthy controls, when corrected for age, body mass index and sex.
      However, these 'normal' GH concentrations must be considered inappropriately high
      in view of the hyperglycaemia in these patients. The low plasma IGF-I
      concentrations might be responsible for the GH over-production.

PMID- 8762732
TI  - The effect of repeated administration of hexarelin, a growth hormone releasing
      peptide, and growth hormone releasing hormone on growth hormone responsivity.
AB  - OBJECTIVE: Hexarelin is a synthetic six-amino-acid compound capable of releasing
      GH in animals and in man. Its mechanism of action is not understood and little is
      known about the GH response after repeated administration. The aim of this study
      was to determine the GH response to the administration of two intravenous boluses
      of hexarelin, growth hormone releasing hormone (GHRH) or hexarelin with GHRH.
      DESIGN: Single boluses of hexarelin (1 microgram/kg), GHRH-(1-29)-NH2 (1
      microgram/kg) or hexarelin with GHRH-(1-29)-NH2 were administered intravenously.
      Each study was performed on two further occasions, with a second bolus being
      administered 60 or 120 minutes after the first. A control study was performed
      giving saline intravenously. Studies were performed in a random order. SUBJECTS:
      Six healthy adult males (25.4-34.1 years) were studied. MEASUREMENTS: Serum GH
      was measured by radioimmunoassay. GH secretion rates were derived from the
      measured serum GH concentrations using the technique of deconvolution analysis.
      RESULTS: The peak GH secretion rate following the first intravenous bolus of
      hexarelin was greater than that following the first bolus of GHRH-(1-29)-NH2 (P <
      0.001), and was greatest following the administration of hexarelin with GHRH-(1
      29)-NH2 (P < 0.001). The coadministration of the two secretagogues resulted in
      peak GH secretion rates significantly greater than the arithmetic sum of those
      following their isolated administration (P = 0.001), demonstrating synergism.
      Compared to saline, the administration of a second bolus of hexarelin, GHRH-(1
      29)-NH2 or both resulted in significant further GH secretion (P = 0.02, P =
      0.002, P = 0.03, respectively). The administration of a second bolus of hexarelin
      or hexarelin with GHRH-(1-29)-NH2 120 minutes after the first bolus resulted in
      lower peak GH secretion rates (P = 0.03). The reductions in peak GH secretion
      rates following the 60-minute boluses were not statistically significant. The
      peak GH secretion rates following the first GHRH-(1-29)-NH2 boluses were similar
      to those following the 60 and 120-minute GHRH-(1-29)-NH2 boluses (P = NS).
      Irrespective of the interval between the boluses of hexarelin with GHRH-(1-29)
      NH2, the peak GH secretion rates following the second boluses were not
      significantly different from the arithmetic sum of those following the
      administration of the second boluses of hexarelin or GHRH-(1-29)-NH2, indicating
      loss of synergism on repeated administration. CONCLUSION: This study shows that
      hexarelin is a potent GH secretagogue active after two successive doses; the
      magnitude of the GH response to the second dose was influenced by the dosing
      interval. Hexarelin and GHRH-(1-29)-NH2 are synergistic, a property which is lost
      after repeated administration. These findings may help our understanding of GHRPs
      and may have implications for the potential use of hexarelin and other GHRPs as
      therapeutic agents.

PMID- 8762733
TI  - Bone mass and metabolism in women aged 45-55.
AB  - OBJECTIVE: Changes in calcium homeostasis and bone mass around the climacteric
      are poorly understood. We examined relations between endocrine factors and
      indices of bone mass and metabolism in healthy women approaching the menopause.
      DESIGN: Cross-section study. PATIENTS: Sixty-eight spontaneously menstruating
      women aged 45-55. MEASUREMENTS: Bone density measured at lumbar spine (LS) and
      femoral neck (FN) using dual energy X-ray absorptiometry and distal non-dominant
      forearm using peripheral quantitative computed tomography. We recorded menstrual
      history, physical activity and dietary calcium, and measured serum calcium,
      phosphate, alkaline phosphatase, osteocalcin, vitamin D, fT3, T4, TSH, PTH, FSH
      and oestradiol (E2), and urinary pyridinoline (PYD) and deoxypyridinoline (DPD)
      excretion. RESULTS: Using serum FSH level as a marker of ovarian function, 63
      subjects could be classified into one of three groups: group A (serum FSH < 10
      U/l, n = 29), group B (10-35 U/l, n = 27) and group C (> 35 U/l, n = 7). Bone
      density fell with declining ovarian function at the LS, FN and forearm trabecular
      (but not cortical) sites. Serum PTH was lower in group A vs B (mean (SD) 2.68
      (0.97) vs 3.52 (1.17) pmol/l, P < 0.05), but similar to group C (2.90 (1.09)
      pmol/l, P = NS). Serum phosphate was elevated in group C compared to groups A and
      B (1.17 (0.15) vs 1.04 (0.11) and 1.05 (0.13) mmol/l, P < 0.05), and urinary PYD
      (61.1 (8.0) vs 50.4 (11.6) and 43.9 (8.1) mumol/mol creatinine) and DPD (15.9
      (3.9) vs 12.0 (3.6) and 11.4 (3.6) mumol/mol creatinine) excretion were also
      increased. There were no significant differences in vitamin D metabolites or
      osteocalcin. Multivariate analysis suggested serum osteocalcin was positively
      related to physical activity and serum 1,25-dihydroxycholecalciferol levels.
      Serum free T3 was positively correlated with urinary DPD excretion, and inversely
      related to serum PTH. In all subjects, serum PTH was related to body weight (r =
      0.38, P = 0.002). CONCLUSIONS: Declining ovarian function before menopause is
      accompanied by reductions in bone mass and altered calcium metabolism. Free T3
      may regulate bone resorption and indirectly modulate PTH release.

PMID- 8762734
TI  - Functional integrity of granulosa cells from polycystic ovaries.
AB  - OBJECTIVE: The polycystic ovarian syndrome is frequently associated with human
      infertility and is a partially characterized syndrome of unknown aetiology. The
      aim of this study was to describe the functional integrity of granulosa cells
      from polycystic ovaries. PATIENTS: Follicular aspirates were collected from
      polycystic ovaries of ovulatory (n = 24) and anovulatory (n = 7) patients.
      Follicular aspirates were also collected from normal ovaries of untreated (n =
      24) and superovulated (n = 10) subjects. All patients were enrolled for the
      recovery of their oocytes for in vitro maturation and fertilization.
      MEASUREMENTS: FSH receptors and apoptosis were measured in the granulosa cells of
      the different patients. FSH-stimulated oestradiol and LH-stimulated progesterone
      production by granulosa cells of the different patients were also measured.
      RESULTS: The binding of 125I-labelled human recombinant FSH to granulosa cells
      from anovulatory subjects with polycystic ovaries was significantly higher than
      that found in granulosa cells from normal (180%) and superovulated (163%)
      ovaries. However, the ligand binding to granulosa cells from ovulatory subjects
      with polycystic ovaries was not significantly higher than that found in normal
      granulosa cells. Also, granulosa cells obtained from anovulatory subjects with
      polycystic ovaries cultured with FSH produced more oestradiol than normal
      granulosa cells but oestradiol production was similar to that of granulosa cells
      from superovulated ovaries (mean +/- SEM, 224.94 +/- 22.02, 24.23 +/- 2.92,
      211.87 +/- 50.39 nmol/l/24 h, respectively). Flow cytometric analysis showed that
      the proportions of viable and apoptotic granulosa cells (mean +/- SDM, 70 +/- 5
      and 7 +/- 1%, respectively) were similar in normal subjects and in those with
      polycystic ovaries. CONCLUSION: We conclude that most of the granulosa cells of
      polycystic ovaries are healthy and non-apoptotic, expressing high levels of FSH
      receptors and highly responsive to this hormone in culture. These data provide
      direct evidence that most of the follicles of polycystic ovaries are not atretic.

PMID- 8762735
TI  - The GnRH challenge test: a quantitative measure of pituitary desensitization
      during GnRH agonist administration.
AB  - OBJECTIVE: The use of GnRH agonists for desensitization of the pituitary is
      widespread in gynaecological practice. For indications such as contraception and
      treatment of uterine leiomyomata partial desensitization may suffice. With
      respect to partial desensitization of the pituitary we have addressed three basic
      questions: (1) Is the degree of pituitary desensitization dependent on the dose
      of agonist used? (2) What is the optimal way to measure the degree of pituitary
      desensitization? (3) Is it possible to create a standard to express the degree of
      pituitary desensitization? DESIGN AND PATIENTS: Twenty-four women were randomized
      into 4 groups of 6 women. To achieve pituitary desensitization, the groups
      received 0.1, 0.25, 0.5 and 1.0 microgram/min GnRH respectively, for 6 weeks.
      MEASUREMENTS: Pituitary desensitization was measured by gonadotrophin levels and
      responses to a 100-micrograms bolus of GnRH and an oestradiol benzoate challenge
      test. RESULTS: The level of LH and the responses of LH and FSH to the GnRH
      challenge showed significant dose-dependent suppression. Multiple regression
      indicated the LH response to the GnRH challenge was the best way to measure
      pituitary desensitization. From the LH responses to the GnRH-challenge a
      'standard curve' was established for the assessment of the degree of pituitary
      desensitization. CONCLUSION: The LH response to the GnRH challenge test is the
      best available measure of pituitary desensitization during GnRH agonist
      treatment.

PMID- 8762736
TI  - 131I-6 beta-iodomethylnorcholesterol scintigraphy: an assessment of its role in
      the investigation of adrenocortical incidentalomas.
AB  - OBJECTIVE: Most incidentally discovered adrenal tumours ('incidentaloma') are
      benign adrenocortical adenomas. It has been suggested that 131I-6 beta
      iodomethylnorcholesterol (IMC) scan could specify the degree of functional
      autonomy of such adenomas depending on whether they prevent contralateral adrenal
      tracer uptake. Our purpose was to examine this hypothesis in a correlated
      scintigraphic and endocrine study. DESIGN: Prospective study evaluating the
      prevalence of unilateral IMC uptake (tumour uptake with no visualization of the
      contralateral adrenal gland) and bilateral uptake (uptake in both the tumoral and
      the contralateral adrenal glands) in patients with unilateral incidentaloma.
      Comparison of adrenocortical function and of IMC scan after dexamethasone (DXM)
      in the two scintigraphic groups thus defined. PATIENTS: Thirty-five patients with
      a unilateral mass highly suggestive of benign adrenocortical adenoma on CT scan.
      MEASUREMENTS: The IMC scan was performed in basal conditions (baseline scan) and
      after DXM (suppression scan). Adrenocortical function assessment included basal
      measurements of 11-deoxycortisol, 17 alpha-hydroxyprogesterone (17-OHP),
      dehydroepiandrosterone sulphate (DHEAS), plasma cortisol and ACTH, urinary free
      cortisol (UFC), overnight and low-dose DXM suppression test, and CRH test.
      RESULTS: The baseline scan showed 16 patients (46%) with unilateral uptake (group
      A) and 19 (54%) with bilateral uptake (group B). Patients in group A exhibited
      lower ACTH values at 0800h (P = 0.05) and higher cortisol values after an
      overnight DXM suppression test (P = 0.02), than did patients in group B. In
      addition, 3 patients in group A failed the overnight and the low-dose DXM
      suppression tests. Adrenal masses were larger in group A than group B (P = 0.04)
      and an inverse correlation was found in the whole population between tumour size
      and ACTH value at 0800h (P = 0.05). On the suppression scan performed in 14
      patients (7 in each group), patients in group A continued to exhibit unilateral
      tumour uptake and bilateral uptake was suppressed in 72% of patients in group B.
      An adrenal mass was removed in 3 patients of group A with confirmed benign
      adrenocortical adenomas. In the post-surgical period, the contralateral gland was
      again visualized in a baseline scan and the hormonal evaluation returned to the
      normal range. CONCLUSION: Unilateral 131I-6 beta-iodomethylnorcholesterol tumour
      uptake is a frequent feature in benign adrenocortical adenomas. Hormonal data and
      scintigraphic profiles obtained after dexamethasone, as well as
      hormonoscintigraphic changes observed after surgery, provide evidence that
      unilateral uptake is related to functioning adenomas with various degrees of
      autononomy and suggest that the 131I-6 beta-iodomethylnorcholesterol scan could
      be a valuable tool for screening 'subclinical' Cushing's adenomas.

PMID- 8762737
TI  - Biochemical cure of recurrent acromegaly by resection of cervical spinal canal
      metastases.
AB  - Pituitary carcinoma with metastatic endocrine secreting tissue is rare. Eight
      cases of malignant, growth hormone-secreting tumours, all metastatic within the
      central nervous system have been previously described. Complete surgical
      resection was not possible and the patients died within 4 years of presentation
      with distant spread. Here we describe the first case of an apparent surgical cure
      of a somatotroph carcinoma metastatic to the cervical spine, documented by
      biochemical assessment and magnetic resonance and radioligand imaging. The
      possibility that intrathecal metastasis of somatotroph tumours may be responsible
      for some cases of treatment resistant acromegaly is discussed.

PMID- 8762738
TI  - Coexistence of bilateral adrenal phaeochromocytoma and idiopathic
      hyperaldosteronism.
AB  - The coexistence of phaeochromocytoma and primary aldosteronism is rare. In the
      four cases reported in the English literature, adrenal gland involvement was
      unilateral. The case we report is unusual in that both adrenal glands were
      affected. Our patient was a 63-year-old man who presented with long-standing
      hypertension and hypokalaemia. Evaluation for secondary hypertension showed
      biochemical evidence of both phaeochromocytoma and primary aldosteronism.
      Bilateral adrenal masses were found on imaging studies. Right total and left
      partial adrenalectomy were performed. Pathological examination revealed bilateral
      phaeochromocytomas, with cortical findings consistent with mild cortical
      hyperplasia. Annual biochemical evaluation over a 2-year period has shown no
      evidence of recurrent disease. To our knowledge, this is the first reported case
      in the English-language literature of phaeochromocytomas involving both adrenal
      glands coexisting with hyperaldosteronism.

PMID- 8762739
TI  - Essential hypertension: should we operate?

PMID- 8762740
TI  - Experts and evidence.

PMID- 8762741
TI  - Sharing resources to create a district drug formulary: a countywide controlled
      trial.
AB  - BACKGROUND: Creating a drug formulary takes considerable time, but merely
      adopting one lacks local perspective and ownership. Sharing resources between
      several practices treads a middle path between these extremes, but is it
      effective? AIM: The aim of the study was to audit the influence of a district
      primary care drug formulary on prescribing by general practitioners. METHOD: A
      controlled trial was carried out to compare prescribing by 50 general
      practitioners from 11 urban and semirural practices in south Bedfordshire that
      participated in creating a district drug formulary with prescribing by all other
      general practitioners in the county. RESULTS: The proportion of prescription
      items that were for drugs listed in the formulary rose significantly in three
      therapeutics groups: cardiovascular (by 7-12% above control practice values);
      musculoskeletal (by 1-11% above control practice values); and obstetrics and
      gynaecology (by 6-9% above control practice values). The number of items
      prescribed per prescribing unit fell significantly in three therapeutic groups:
      musculoskeletal (by 1-7% below control practice values); nervous (by 7-12% below
      control practice values); and nutrition and blood (by 15-21% below control
      practice values). The estimated saving resulting from the creation of the
      formulary was 150,000 pounds (3000 pounds per doctor) per year. CONCLUSIONS:
      Sharing resources between practices to create a district-wide primary care drug
      formulary can lead to changes in prescribing and reduce costs sustained over 3
      years.

PMID- 8762742
TI  - Prevalence of asthma and COPD in general practice in 1992: has it changed since
      1977?
AB  - BACKGROUND: Asthma and COPD are common diseases of the airways which are mainly
      diagnosed and treated in general practice. AIM: Various studies have reported an
      increase in the morbidity of asthma and COPD. There are two possible reasons for
      such an increase. The first is an apparent increase caused by using different
      criteria in defining asthma/COPD, and by increased awareness of the disease by
      doctors and patients. The second is a real increase caused by an increase in the
      prevalence of airway pathology. The aim of this study was to determine the cause
      of the observed increase in morbidity. METHOD: In 1977, a sample of 2328 adults
      from the general population were screened for asthma and COPD. Those screened
      were then divided into five sub-groups (grades 1-5), according to severity of:
      (1) respiratory symptoms; and (2) loss in FEV1. The number of patients who were
      not known to the general practitioner prior to the screening as having asthma or
      COPD grades 1-5 were also assessed. In 1992, we studied a different sample of
      1184 adults of the general population in the same area. We used the same criteria
      as in 1977 to analyse our results. The number of patients not known to the
      general practitioner prior to the screening was also studied. RESULTS: The
      overall prevalence (grades 1-5) of asthma and COPD has increased from +/- 19% in
      1977 to +/- 31% in 1992 (range 21-42). The main reason for this is an increase in
      prevalence of very mild to moderate asthma and COPD (grades 1-3) from 17% in 1977
      to 27% in 1992. The prevalence of severe cases (grades 4-5) increased from 2% in
      1977 to 4% in 1992. In 1992, around 65% of the patients were not known to the
      general practitioner as having any grade of asthma or COPD. This was only
      slightly lower than the 72% in 1977. All patients with a severe disease (grade 5)
      were known to the general practitioner. CONCLUSIONS: There is a real increase in
      the prevalence of asthma and COPD, caused predominantly by an increase in the
      number of mild cases. The percentage of patients not known to the GP were
      predominantly mild cases.

PMID- 8762743
TI  - Screening for colorectal cancer: a general-practice-based study.
AB  - BACKGROUND: A 2-year study was undertaken to determine the best way of setting up
      faecal occult blood screening for colorectal cancer in a single general practice
      in north Birmingham, a district with no pre-existing hospital-based screening
      programme for colorectal cancer. This programme was set up in close collaboration
      with the Departments of Surgery and Biochemistry at the local Good Hope Hospital
      Trust. This facilitated joint meetings between the staff of these hospital
      departments and the practice manager, who was responsible for organization of the
      study at the Hawthorns Surgery and also supervised the day-to-day running of the
      programme. Essentially, the study was organized and run by the practice manager
      and nurse. AIM: The study was undertaken to prepare the way for other general
      practices in north Birmingham to screen selected populations for colorectal
      cancer. METHOD: A Haemoccult test kit was posted to patients together with an
      explanatory letter. The design of the screening programme was similar to the
      design of the 'screened arm' of the Medical Research Council (MRC) colorectal
      screening trial in Nottingham. On completion of the programme, questionnaires
      were posted to 100 responders and 100 non-responders to assess the level of
      patient acceptability for the screening study. A total of 3509 patients (1599 men
      and 1910 women) were invited to take part in the screening. RESULTS: The response
      rate was 55.4%. Thirty-nine patients were referred from the screening study for
      further investigation. Colonoscopy identified nine adenomas in nine patients, and
      a further 12 patients were found to have colorectal carcinoma. CONCLUSIONS: The
      findings from the study suggest that this method could be used as a model for
      other general practices introducing colorectal screening using Haemoccult.

PMID- 8762744
TI  - Influences on prescribing in non-fundholding general practices.
AB  - BACKGROUND: The experience from general practice fundholding suggests that
      financial incentives may influence prescribing; guidelines and hospital
      prescribing are two other suggested influences. AIM: A study was undertaken to
      establish general practitioners' attitudes to a financial prescribing incentive
      scheme, the presence and use of guidelines, and the influence of prescribing
      initiated within secondary care. METHOD: A postal questionnaire survey of non
      fundholding general practices in the former Northern Region was conducted.
      RESULTS: Practices' thinking and subsequent decisions about the incentive
      prescribing scheme were most often influenced by discussions within the practice
      (45%). Those practices that achieved their savings under the incentive scheme
      were less likely than those not achieving savings to feel that the target was not
      achievable, the time scale was unacceptable, and that the philosophy behind the
      scheme was unacceptable. Forty-five per cent of practices received advice from
      neither a medical nor a pharmaceutical adviser; 27% of practices received advice
      from both, 12% from a medical adviser only and 16% from a pharmaceutical adviser
      only. Of the practices that tried to make their target savings, 91% intended to
      increase generic prescribing; fewer than one-third of practices mentioned any
      other measure. Prescribing guidelines were reported by a minority of practices,
      although reported rates of use were high when these were present. Clinical
      guidelines for three conditions, asthma, diabetes and hypertension, were present
      in more than 50% of practices; 25% of practices had no clinical guidelines.
      Hospital prescribing was reported as 'always' or 'usually' influencing
      prescribing for diabetes by 57% of respondents, ischaemic heart disease by 55%,
      peptic ulceration by 49%, asthma by 42% and hypertension by 39%. CONCLUSIONS:
      General practitioner prescribing is influenced by a complex web of factors, with
      no single factor pre-eminent. To understand this area further, there is a need to
      take each of these areas and ascertain the match between doctors' perceptions and
      actual practice.

PMID- 8762745
TI  - Gender differences in general practitioners at work.
AB  - BACKGROUND: The proportion of female general practitioners is steadily
      increasing. AIM: To compare male and female general practitioners with respect to
      their job satisfaction and professional commitments within and outside their
      practices. METHOD: A questionnaire was sent to all 896 general practitioner
      principals with patients in Staffordshire in 1994. The main elements were: job
      satisfaction (on a five-point scale) from eight possible sources; whether
      personal responsibility was taken for 12 different practice tasks; and
      professional commitments outside the practice. RESULTS: A total of 620 (69%)
      general practitioners responded. Female doctors derived more satisfaction than
      male doctors from relationships with patients (P = 0.002). Female doctors were
      more likely to be working in training practices, and were likely to be on-call
      less and to work fewer sessions. Male general practitioners were more likely to
      take lead responsibility for practice computers, minor surgery, meeting external
      visitors and finance, whereas female practitioners were more likely to be
      responsible for looking after women patients' health. CONCLUSION: Considerable
      differences were found between male and female general practitioners. These
      differences are likely to have an increasing impact as the percentage of female
      general practitioners continues to rise.

PMID- 8762746
TI  - Use of a postal questionnaire to estimate the likely under-diagnosis of asthma
      like illness in adults.
AB  - BACKGROUND: Asthma is thought to be under-diagnosed. AIM: To estimate how many
      adults in two practices may have unknown asthma-like illness. METHOD: Results
      from a postal respiratory questionnaire, sent to 11,206 adults registered with
      two practices, were linked with practice records to identify patients who may
      have unknown asthma-like illness. RESULTS: The questionnaire replies were almost
      identical in both practices; 30.4% of respondents [95% confidence interval (CI)
      29.4-31.4] reported wheezing and 14.1% (95% CI 13.3-14.9) had been woken by
      breathlessness during the previous year. Using a simple scoring system, 1112
      (13.8%) of the respondents were judged possibly to have asthma-like illness; 529
      (6.6%) had not previously been diagnosed as having asthma and had not received
      asthma treatments. CONCLUSION: The frequency of asthma-like symptoms was high. A
      large proportion of adults in the practices may have an unknown asthma-like
      illness which warrants further evaluation.

PMID- 8762748
TI  - General practitioners and occupational health services.
AB  - BACKGROUND: Occupational physicians and general practitioners often appear to
      differ in their attitudes to the provision of health screening, health promotion
      and vaccination in the workplace. AIM: This study aimed to explore the attitudes
      of occupational physicians and general practitioners to particular aspects of
      workplace health services. METHOD: Anonymous piloted postal questionnaires were
      sent to 400 UK general practitioners and 300 occupational physicians. RESULTS:
      Questionnaires were returned by 260 general practitioners (65%) and 223
      occupational physicians (74%). There are differences between the specialties in
      attitude to specific health screening and vaccination at work, and to the role of
      occupational health services in helping the disabled, but greater agreement on
      the usefulness of workplace health promotion. CONCLUSION: General practitioners
      may misunderstand the role, responsibilities and priorities of occupational
      health services. Further educational work needs to be done to overcome
      communication difficulties between the specialties.

PMID- 8762747
TI  - The views of general practitioners on community carrier screening for cystic
      fibrosis.
AB  - BACKGROUND: Recent developments in molecular genetics have made it possible to
      identify carriers of the cystic fibrosis (CF) mutation, regardless of family
      history, before they have an affected child. Using these techniques, population
      or 'community' carrier screening can offer informed reproductive choice to
      individuals and couples who would not otherwise know of their risk of having a CF
      child. AIM: This study set out to assess the views of general practitioners (GPs)
      on community carrier screening for CF and to consider the factors that influence
      their willingness to offer it themselves. METHOD: A self-administered
      questionnaires was sent to all 616 GPs in four areas of North Thames (West)
      Region. RESULTS: Two-thirds of respondents indicated that identifying carrier
      couples to offer genetic counselling before conception was a very important
      benefit of community carrier screening. Two-thirds felt that general practice was
      the most appropriate place in which to offer it, and similar proportions that the
      most appropriate times to do so were when a close relative was diagnosed and when
      seeking family planning. About half wanted to offer community carrier screening
      themselves; this was related to experience with CF patients and CF carrier
      testing, and estimates of the numbers of CF carriers in the practice.
      CONCLUSIONS: There is considerable support among GPs for community carrier
      screening for CF in general practice, particularly in the context of family
      planning services. Knowledge and experience of CF increase GPs' willingness to
      offer it themselves.

PMID- 8762749
TI  - Standardization of health assessments for patients aged 75 years and over: 3
      years' experience in the Forth Valley Health Board area.
AB  - BACKGROUND: The new contract for general practitioners (GPs) was introduced in
      1990. This required all GPs to offer their patients aged 75 years of over an
      annual assessment. AIM: The study aimed to determine if 3 years' experience had
      resulted in standardization of the way in which health assessments for patients
      aged 75 years and over are carried out. METHOD: The study was carried out in
      1993. Questionnaires were sent to the principal partners of all 55 general
      practices in the Forth Valley Health Board (FVHB) area. The main outcome measures
      were the fulfilment of contractual requirements and standardization of the health
      assessment process. RESULTS: Completed questionnaires were returned by 49
      practices (89%) Eighty per cent (39 practices) had drawn up their own assessment
      programme in 1990. Responsibility for assessments was most often (41 practices)
      shared between different members of the primary care team (84%). Although most
      practices satisfied contractual requirements, there were wide variations in
      approach, potentially influencing outcome. CONCLUSION: Despite three years'
      experience, no standardized approach to the health assessment of patients aged 75
      years and over has been developed. Purchasers of health care require information
      on the needs of their client population, and this should be available in an
      accessible, standardized form. There is an urgent need for a review of the way in
      which the 1990 contract has been implemented to standardize health assessments
      and improve effectiveness in meeting its original aims.

PMID- 8762751
TI  - Mental health promotion for young adolescents in primary care: a feasibility
      study.

PMID- 8762750
TI  - Steroid injections for shoulder disorders: a systematic review of randomized
      clinical trials.
AB  - BACKGROUND: Patients with shoulder disorders are believed to benefit considerably
      from steroid injections. However, the controversy about their efficacy persists.
      AIM: The study was designed to assess the efficacy of steroid injections for
      shoulder disorders. METHOD: A systematic computerized literature search in
      Medline (Index Medicus 1/1966-10/1995) and Embase (Excerpta Medica 1/1984
      10/1995) was conducted, supplemented with citation tracking of all relevant
      publications. Studies published before November 1995 were selected if steroid
      injections were randomly allocated to patients with shoulder disorders and when
      clinically relevant outcome measures were reported. Because the validity of study
      outcomes depends heavily on the strength of methodological quality, the methods
      were assessed systematically by two 'blinded' independent reviewers. This
      resulted in a method score (maximum 100 points) that was based on four
      categories: study population, interventions, measurement of effect, and data
      presentation and analysis. Confidence intervals for the differences between
      groups in success rates were calculated in order to summarize the efficacy of
      steroid injections. RESULTS: Only three out of the 16 studies scored more than 50
      points, indicating a generally poor quality of methods. Most studies reported
      small sample sizes. The flaws most often found were incomparability of co
      interventions and poor blinding of therapist. The methods assessment was
      frequently hampered by incomplete information about randomization, prognostic
      comparability, compliance, outcome measures included, blinding of patients and
      blinding of outcome measurement. CONCLUSIONS: The evidence in favour of the
      efficacy of steroid injections for shoulder disorders is scarce. The methods of
      most studies appear to be of poor quality. The few studies that appear to be
      credible do not provide conclusive evidence about which patients at what time in
      the course of shoulder disorders benefit most from steroid injections.

PMID- 8762752
TI  - Women's views of their first antenatal visit.

PMID- 8762753
TI  - Direct access to CT screening.

PMID- 8762754
TI  - Catecholaminergic interplexiform cells in the retina of lizards.
AB  - An immunohistochemical study of the distribution of tyrosine hydroxylase has been
      performed in the retina of lizards of the genera Podarcis, Anolis and Tarentola.
      Immunoreactive cells extending their processes into the inner plexiform layer
      were observed in all three species. Reactive fibres in the outer plexiform layer
      were also seen in Podarcis and Anolis, and hence they possess not only amacrine
      but also catecholaminergic interplexiform cells. The retina of Anolis also showed
      reactive fibres aposed to the photoreceptors near the central fovea. The role of
      this outer retinal innervation on dopamine-dependent light-adaptive phenomena is
      discussed from a comparative perspective.

PMID- 8762755
TI  - GABA immunopositive axons in the optic nerve and optic tract of macaque monkeys.
AB  - Using an antibody to gamma-aminobutyric acid (GABA), we examined the optic nerves
      and optic tracts from macaque monkeys at the light and electron microscopic
      levels to determine if there is a possible inhibitory projection from the retina
      to the brain. All of the monkeys (n = 5) had GABA immunopositive axons that were
      evenly distributed in their optic nerves. These immunopositive axons were
      slightly larger than the axons around them and comprised an average of 2.6% of
      the axons in the nerves. Thus, their estimated total was about 44,000 axons per
      nerve. In the optic tracts, the GABA immunopositive axons were not distributed
      evenly, but were concentrated mostly in the ventromedial part, indicating that
      this retinal pathway probably goes to a midbrain destination such as the superior
      colliculus. The present findings provide further evidence that there is a
      GABAergic retinal projection to the brain in primates with currently unknown
      physiological influences.

PMID- 8762756
TI  - Daily variations in cGMP, guanylate cyclase and phosphodiesterase in the golden
      hamster retina.
AB  - Daily variations in cGMP, guanylate cyclase and phosphodiesterase activity in
      golden hamster retina were studied. Cyclic GMP content exhibited significant
      variations throughout the 24-hr cycle with maximal values during the dark phase.
      In order to establish the relative participation of nucleotide synthesis and
      breakdown during a 24-hr cycle, guanylate cyclase and phosphodiesterase activity
      were measured in hamsters killed at eight intervals. Guanylate cyclase activity
      increased at night, peaking at 22.00 hr. Phosphodiesterase activity did not
      change significantly throughout the light-dark cycle. Light exposure during the
      night inhibited the nocturnal increase in cGMP content and guanylate cyclase
      activity, while phosphodiesterase remained unchanged. From these results, it
      might be presumed that in response to continuous (in a range of hr) light or dark
      stimuli, the retina would process the photic signal in a different way from that
      in the short term (in a range of msec).

PMID- 8762757
TI  - Effect of spatial scale and background luminance on the intensive and spatial
      nonlinearities in texture segregation.
AB  - Perceived segregation between element-arrangement textures is affected both by
      spatial scale and background luminance. The effects on the spatial nonlinearity
      are consistent with the proposed structure for complex (second-order) channels.
      The effects on the intensive nonlinearity are not consistent with an early, local
      nonlinearity but are consistent with either (i) a relatively early, local,
      nonlinearity occurring before the spatial frequency channels but after a
      sensitivity-setting stage, or (ii) inhibitory interaction among channels modeled
      as a normalization network. Thus the texture intensive nonlinearity comes after
      sensitivity to spatial frequency and background luminance has been determined.
      For six of seven observers, the texture intensive nonlinearity was compressive by
      10% contrast for both increments and decrements (at high background luminance,
      large spatial scale.

PMID- 8762758
TI  - Temporal limits of brightness induction and mechanisms of brightness perception.
AB  - The luminance of a squarewave grating was modulated in a manner such that every
      other stripe temporally varied between bright and dark and the intervening
      stripes had constant luminance. This produces brightness induction in the
      constant stripes, roughly in antiphase to the luminance modulation. We used this
      stimulus as a probe to explore the temporal properties of brightness induction
      and the mechanisms determining perceived brightness. Over a range of spatial
      frequencies we measured: (1) the highest temporal frequency at which brightness
      induction occurs; (2) the magnitude of induced brightness; and (3) the temporal
      phase of the induced brightness modulation. We find that brightness induction
      ceases with luminance modulation above a cutoff temporal frequency that depends
      on spatial frequency. The magnitude of induced brightness modulation is greatest
      at low spatial frequencies and low temporal frequencies. Induced brightness lags
      behind the luminance modulation and this phase lag increases as spatial frequency
      decreases. All of these findings can be understood as consequences of an
      induction process that takes longer to complete as the induction region increases
      in size.

PMID- 8762759
TI  - The effect of illuminant position on perceived curvature.
AB  - In shaded scenes surface features can appear either concave or convex, depending
      upon the viewer's judgement about the direction of the prevailing illumination.
      If other curvature cues are added to the image this ambiguity can be removed.
      However, it is not clear to what extent, if any, illuminant position exerts an
      influence on the perceived magnitude of surface curvature. Subjects were
      presented with pairs of spherical surface patches in a curvature matching task.
      The patches were defined by shading and texture cues. The perceived curvature of
      a standard patch was measured as a function of light source position. We found a
      clear effect of light source position on apparent curvature. Perceived curvature
      decreased as light source tilt increased and as light source slant decreased. We
      also found that the strength of this effect is determined partly by a surface's
      reflectance function and partly by the relative weight of the texture cue. When a
      specular component was added to the stimuli, the effect of light source
      orientation was weakened. The weight of the texture cue was manipulated by
      disrupting the regular distribution of texture elements. We found an inverse
      relationship between the strength of the effect and the weight of the texture
      cue: lowering the texture cue weight resulted in an enhancement of the illuminant
      position effect.

PMID- 8762760
TI  - A simple mechanism for detecting low curvatures.
AB  - We measured thresholds for detecting the direction of curvature in slightly bent
      stimuli such as arcs and sinusoidal lines, and the direction of bend in chevrons
      and trapezoids in an initial experiment. Stimulus length varied over a wide range
      from 8.3 to 267 min arc. For sufficiently long stimuli, the angle between the
      stimulus and its chord was constant at 0.2-0.3 deg at detection threshold. The
      constant threshold implies that performance might be limited by the sensitivity
      of a single mechanism, in this case one that detects the orientation difference
      between the stimulus and its imaginary chord. In a second experiment, we
      investigated the two-dimensional extent of curvature sensitive units by measuring
      thresholds for detecting curvature of arcs that were flanked by straight lines on
      both sides. Thresholds remained unaffected at flank distances above 6 min arc but
      increased at lower distances independently of arc length, compatible with the
      assumption of a local, orientation sensitive mechanism. In a third experiment, we
      measured curvature detection with stimuli of different shapes to examine
      psychophysically the putative role of odd side margin receptive fields. We
      propose that low curvatures might be analysed by orientation sensitive units with
      a size around 20 x 8 min arc.

PMID- 8762761
TI  - The tilt aftereffect in plaids and gratings: channel codes, local signs and
      "patchwise" transforms.
AB  - The perceived structure of a suprathreshold plaid made from two sinusoidal
      gratings tilted +/- 45 deg from vertical usually resembles a blurred
      checkerboard. Physically increasing the tilt of the components away from vertical
      elongates the pattern horizontally, yielding rectangular checks. We asked whether
      illusory tilt of the components induced by adaptation to a vertical grating would
      also give apparent elongation of the checks. Using a staircase method, we found
      that after adaptation the component orientations had to be set 3-4 deg closer to
      vertical to maintain a square, checkerboard-like appearance, implying that the +/
      45 deg plaid did appear elongated. This result suggests that the tilt
      aftereffect adaptation not only distorts the orientation of 1-D patterns but can
      also change the relative location of features, even when their orientation is not
      altered. This is not easy to explain within filter models that (often implicitly)
      assume each receptive field carries a fixed "local sign" indicating its position
      within the retinal array. We consider a representation in which localized patches
      of the image are encoded by the coefficients of a 2-D Fourier-like transform.
      With a simple subtractive model of adaptation, we show that the spatial
      information carried by each patch would be distorted in just the way observed for
      plaids and gratings. The fact that perceived structure is both distorted and
      coherent, not fragmented, after adaptation suggests an additional, more global
      process whereby local patches are combined to form a coherent, composite "neural
      image". We offer a simple principle that could establish this coherence. If the
      positions of local patches are adjusted so as to maximize the contrast energy of
      the composite image, then the spatial distortions of the patches (induced by
      selective adaptation) are carried through to the global structure of the
      composite. Thus, the conflict between channel codes and local signs is resolved,
      but perceptual distortion is the result.

PMID- 8762762
TI  - Visual search for colour targets that are or are not linearly separable from
      distractors.
AB  - D'Zmura [(1991) Vision Research, 31, 951-966] reported qualitative differences in
      visual search rates for a target colour in a background of differently coloured
      distractors depending on their colour configuration in CIE(x,y) space. A target
      colour that was chromatically mid-way between the distractor colours resulted in
      steep search slopes. A target off the distractor-distractor line, "popped out".
      We replicated his finding in several loci, investigated several potential
      confounds, and discovered boundary conditions for the phenomenon: for a given
      target, the effect of collinearity dissipates with increasing distractor
      distractor colour difference. Furthermore, within limits, performance was
      dependent on the target to distractor-line distance.

PMID- 8762763
TI  - Localization of element clusters: multiple cues.
AB  - The visual system commonly has to estimate the relative location of a textured
      region but the stimulus features used to perform that task are yet to be
      determined. The use of centroid, midpoint and peak activity cues would all be
      reasonable. In the current experiment an attempt was made to assess the relative
      efficacy of these three cues. The observers were required to indicate whether a
      cloud of either 3, 10 or 100 elements was located to the left or right of an
      imaginary line formed between two reference elements. Performance was compared to
      that expected from the use of the three cues. It was concluded that the cue used
      varied as the characteristics of the cloud changed and therefore that the visual
      system is not restricted to the use of a single cue type when localizing object
      clusters.

PMID- 8762764
TI  - Can random-dot stereograms serve as a model for the perception of depth in
      relation to real three-dimensional objects?
AB  - The ability to perceive depth in a random-dot stereogram is a valuable test for
      the perception of retinal image disparities, whether they arise from the viewing
      of a stereogram or from the viewing of a real 3-D object. However, a stereogram
      cannot be regarded as a proper model for the perception of depth in the case of a
      real 3-D object. This conclusion comes out most clearly in relation to changes in
      viewing distance. Whereas the viewing of real objects and stereograms both obey
      the rules of size constancy, this is not the case with depth constancy. With
      changes in viewing distance, the viewing of real objects obeys the rules of depth
      constancy. By contrast, the magnitude of the depth intervals in a stereogram are
      not constant but appear to increase in direct proportion to the increase in
      viewing distance. In a stereogram these changes in the amplitude of the depth
      intervals are based on the same mechanisms as those responsible for size
      constancy.

PMID- 8762765
TI  - Binocular eye movements caused by the perception of three-dimensional structure
      from motion.
AB  - We report that the perception of three-dimensional structure from monocular two
      dimensional images changing over time--the kinetic depth effect (KDE)--can evoke
      binocular eye movements consistent with a three-dimensional percept. We used a
      monocular KDE stimulus that induced a vivid perception of a rigid three
      dimensional sphere rotating in space. The gaze directions of both eyes were
      measured while observers pursued the motion of a patch on the surface of the
      perceived sphere as it went through a complete revolution. We found that the eyes
      converged when the patch was perceived on the front surface of the KDE sphere and
      diverged when the patch was perceived in the back. The pattern, magnitude and
      dynamics of binocular eye movements observed in the KDE experiment resembled
      those obtained when subjects viewed binocularly a light-emitting diode (LED)
      rotating in space and to the responses obtained with a dynamic stereogram
      simulating a rotating random dot sphere. Thus, the perception of three
      dimensional structure from motion, stereopsis, or motion and stereopsis combined,
      were effective in guiding binocular eye movements.

PMID- 8762766
TI  - Attentional frames, frame curves and figural boundaries: the inside/outside
      dilemma.
AB  - Attended and unattended regions of the image array are viewed often as binary
      complements to one another, with a well-defined boundary between them. A simple
      experiment shows otherwise: if the contour of a simple convex shape is perturbed
      to create a distinctive texture, it is typically the outside of the contour that
      provides the basis for similarity judgement, not the inside. The introduction of
      the appropriate task, however, can make the inside part of the contour become
      more salient. A similar result occurs for concave shapes, such as a C, where
      notions of containment are not easily specified. These observations suggest that
      figure boundaries are difficult to define objectively and that the setting of an
      attentional reference frame plays a key role in object description. We propose
      that this frame is part of a virtual, transparent blackboard or "clearboard",
      bound to the scene, not to the image.

PMID- 8762767
TI  - Blurring the image does not help disabled readers.
AB  - Previous research has found that poor readers performed a visual search task more
      slowly than good readers, but that this difference was virtually eliminated by
      blurring of the search array. Whereas blurring had little effect on the
      performance of the good readers, it led to a dramatic improvement in the search
      rate of the poor readers. The present study set out to replicate this research
      with groups of 10-12 yr old disabled and average readers but with methodological
      improvements in the procedure and the analysis. It was found that the disabled
      readers performed the search task as well as the average readers, and that
      blurring of the display conferred no advantage on either group. The results are
      discussed in relation to the transient deficit theory of reading disability.

PMID- 8762768
TI  - On a failure to replicate: methodologically close, but not close enough. A
      response to hogben et al.
AB  - Williams, Brannan and Lartigue (1987) (Clinical Vision Science, 1, 367-371)
      reported that poor readers took significantly longer to search letter arrays for
      a target than did good readers. In addition, they reported that blurring the
      letter arrays leads to faster search times for poor readers and a loss of the
      significant differences between the groups seen with unblurred displays. In a
      recent attempt to replicate these findings, Hogben et al. (1996) (Vision
      Research, 36, 1503-1507) found no differences in search rates between good and
      poor readers using unblurred arrays, and no differences in search rate between
      the groups when blurred arrays were used. In the present article, we have
      compared these two research efforts, and a third paper on the same topic, with
      regard to methodological factors in an attempt to understand how these two
      different results could occur. It is our belief that the letter spacing employed
      in the two studies may account for the difference and should be the focus of
      future studies of the original effect.

PMID- 8762769
TI  - Visual field defects due to spectacle frames: their prediction and relationship
      to UK driving standards.
AB  - One male and one female subject wore a selection of ten current spectacle frames
      in random order. Monocular visual fields were assessed using an Aimark perimeter
      in accordance with UK Driver and Vehicle Licensing Authority (DVLA) guidelines.
      Of the ten frames, seven plastic frames produced an absolute scotoma intruding
      into a 120 degrees x 40 degrees 'letterbox' area acting as a driving visual field
      template. Three metal frames gave a relative scotoma; however, our apparatus was
      too insensitive to plot these scotomata. Relevant frame and patient parameters
      were measured and entered into a computer program which enabled theoretical
      visual field defects due to a spectacle frame to be calculated. Good agreement is
      shown to be possible between actual and computed visual field defects. Spectacle
      frames can and frequently do cause visual field defects which may affect a
      driver's fitness to drive. Our data also show that a frame which allows an
      adequate field of vision at night could cause a marked visual field defect during
      daylight hours. A model and rule-of-thumb are given to determine the size of
      these potential defects and suggestions are given to minimise or eliminate them.

PMID- 8762770
TI  - A new non-contact corneal aesthesiometer (NCCA).
AB  - A novel method for testing the corneal nerve function, through non-invasive
      measurement of corneal sensitivity, is presented. The method of using a
      controlled pulse of air to stimulate the corneal surface is described. Technical
      information of the aesthesiometer's construction is given. Examples of the
      ability of the instrument to accurately locate the corneal sensitivity threshold
      using either a method of constant stimuli, or a method of limits, is described
      for 14 normal, non-lens wearing eyes. Measurements are made in millibars of air
      pressure required. Mean normal values found were 0.342 +/- 0.068 millibars.
      Discussion is made of the instrument's mode of action, its advantages over other
      invasive instruments, and potential clinical application.

PMID- 8762771
TI  - The misting characteristics of spectacle lenses.
AB  - When a spectacle wearer enters a warm environment after having been in a cooler
      one, his/her spectacles may 'mist up' due to the formation of condensation on the
      lens surface. Both the physical properties of the spectacle lens and a number of
      environmental factors determine how long spectacles take to demist. The relative
      misting performance of crown glass, CR39 and polycarbonate spectacle lenses were
      assessed using a novel technique. A box in which the environmental conditions
      could be controlled was used first to cool the lens and then to warm it. This
      change in temperature caused condensation to form on the lens surface. By
      projecting the image of a grating through the lens onto a linear array of
      photodiodes it was possible to measure the contrast transmission of the spectacle
      lens as it demisted. Each lens type misted and demisted in a characteristic way.
      The polycarbonate lens demisted more rapidly than the CR39 lens which, in turn,
      demisted more rapidly than the glass lens. This indicates that polycarbonate
      spectacle lenses should be used in conditions where the adverse effects of
      spectacle misting need to be minimised.

PMID- 8762772
TI  - An evaluation of the keratoconic cornea using computerised corneal mapping and
      ultrasonic measurements of corneal thickness.
AB  - Reports indicate the presence of up to three independent cone shapes in
      keratoconus (round/oval/global) but the preponderance of one cone over another is
      unclear. This work evaluates keratoconic corneal topography and corneal thickness
      using videokeratoscopy and ultrasound pachometry, respectively. An EyeSys
      videokeratoscope (VKS) (EyeSys Laboratories, Houston, TX, USA) was used to assess
      the topography of 54 keratoconic eyes (27 subjects) and 27 age-matched normals.
      In addition, ultrasonic pachometry measurements were made over 14 known areas in
      normal and keratoconic eyes. Corneal thinning was significant for all keratoconic
      areas measured except for the far temporal cornea. A correlation between corneal
      radius and thickness was evident. Analysis of cone shape revealed a potential
      fourth variety: the asymmetric bow-tie cone. Further topographic evaluation of
      this cone entity using the VKS revealed its dependence on gaze direction which
      may account for apparent differences in progression patterns between round and
      bow-tie cones.

PMID- 8762773
TI  - Optical consequences of asymmetries in normal corneas.
AB  - A survey of videokeratographs of normal corneas shows many with substantial
      peripheral asymmetries. For sufficiently large pupils (5.5 mm in this study)
      these asymmetries lead to coma-like axial aberrations large enough to produce
      measurable losses in vision in a number of cases. Starting from the output of a
      videokeratographic instrument, a method of estimating the optical effects of
      corneal asymmetries using Zernike circle polynomials is outlined. It is further
      shown that in a first approximation corneal asymmetries can be identified with
      the primary aberration coma and that this aberration is approximately due to a
      uniform gradient of refractive power across the cornea. Calculations for a
      representative case predict that a significant improvement in modulation transfer
      would follow from correction of this aberration.

PMID- 8762774
TI  - Application of a modified keratometer in the study of corneal topography on
      Chinese subjects.
AB  - A corneal topography study was carried out on Hong Kong Chinese subjects using a
      modified keratometer. The Chinese corneal topography measured by this modified
      keratometer was similar to other studies using the Wesley-Jessen Photo Electronic
      Keratoscopy (PEK) System 2000. The mean p-values along the horizontal meridian
      and the vertical meridian were 0.82 and 0.87, respectively. A negative
      correlation was found between the p-value and the central corneal radius along
      the horizontal meridian which may indicate that a steeper central cornea will
      have a greater p-value. However, the correlation coefficient of 0.56 was not too
      certain for this conclusion to be drawn. A difference of 0.04 was found between
      the horizontal p-value and the vertical p-value, which may be a result of the
      tight lid tension along the vertical meridian. This modified keratometer can be
      considered as an inexpensive instrument for the study of corneal topography.

PMID- 8762775
TI  - Determination of the radius of curvature of the anterior lens surface from the
      Purkinje images.
AB  - A new method for calculating the radius of curvature of the anterior surface of
      the crystalline lens from the measured heights of the Purkinje image PI and PIII
      is given. Equations are developed for determination of the radius of curvature of
      the equivalent mirror for three configurations commonly used in phakometry. The
      method can be applied to targets at any distance from the corneal vertex, for
      both a stationary target mounted independently of the camera, and for a mobile
      source attached to the camera where the distance of the target to the corneal
      vertex will change as the camera is refocused from image PI to PIII. The
      situation where only one recording is made of images PI and PIII, where the
      camera is focused on image PI, and the height of the defocused image of PIII is
      measured is also considered. The errors in calculating the anterior lens radius
      with the equivalent mirror method if no allowance is made for an object at a
      finite distance is examined. The new method described is an alternative to
      collimating targets to overcome the errors in phakometry that occur with targets
      at finite distances.

PMID- 8762776
TI  - Optimal photographic imaging of the bulbar conjunctival vasculature.
AB  - A method for imaging the conjunctiva to yield greater contrast between the
      vasculature and the scleral background, by optimisation of the imaging system, is
      described. A simple modification to the image capture system, based on first
      principles calculations, is shown to give images with much improved information
      content. This will enhance the assessment of hyperaemic changes induced by
      foreign materials, indicating the degree of biocompatibility, e.g. with contact
      lenses and ophthalmic medications. Observation of vascular abnormalities
      associated with pathological conditions may assist in their diagnosis and monitor
      progressive changes.

PMID- 8762777
TI  - Determination of the total attenuation coefficient for six contact lens materials
      using the Beer-Lambert law.
AB  - The Beer-Lambert law has been used to determine the total attenuation
      coefficient, mu t, of three hard and three soft contact lens materials. The three
      hard contact lens materials were PMMA, Polycon II and Boston IV whereas the 3
      soft materials were chosen with differing water contents of 38, 55 and 70%,
      respectively. The total attenuation coefficients of all six materials were
      obtained from measurements of the axial transmission at 632.8 nm of a series of
      plano powered lenses varying in axial thickness from 0.5 to 3.5 mm. The value of
      the total attenuation coefficient depends on both scattering and absorption and
      hence PMMA and Boston IV, which both incorporated a handling tint, showed
      significantly higher values (P < 0.0001) of mu t (0.562 +/- 0.010 mm-1 and 0.820
      +/- 0.008 mm-1, respectively) than Polycon II (mu t = 0.025 +/- 0.005 mm-1). A
      comparison between Polycon II and the three hydrated soft contact lens materials
      showed a significant increase (P < 0.02) in the total attenuation coefficients
      for the 38% and 55% water content materials, and a weakly significant increase
      for the 70% water content soft lens material (P < 0.1). On the assumption that
      the absorption coefficients of these four materials are approximately constant,
      then this change would be due to an increase in the scattering coefficient of the
      material and could contribute to an increase in intraocular scatter. No
      significant difference (P > 0.5) was found between any of the hydrated soft
      contact lens materials tested.

PMID- 8762778
TI  - Spatial interference with vertical pistol sight alignment.
AB  - When competition pistol shooters aim, they perform four basic visual alignment
      tasks. With optimal stimuli such tasks can be performed with exquisite
      sensitivity. However, pistol sights and the target may not constitute the optimal
      stimuli, and this may impose limits on how well shooters perform. By simulating
      pistol sights and targets on a computer monitor, we investigated how the vernier
      task of aligning the top edges of the front and rear pistol sights was affected
      by the proximity of the target aiming mark. Alignment random error in this task,
      an analogous measure to vernier acuity, was unaffected by the proximity of the
      aiming mark; however, alignment systematic error did change significantly as the
      proximity of the aiming mark changed. This effect was unlikely to significantly
      change pistol shooting performance as shooters can adjust their sights to
      compensate for systematic errors. Likewise, compared to the vertical spread of
      shots on the pistol target, alignment random error was extremely small (only 10 s
      arc), which implies that other sources of variation limit pistol shooting
      performance.

PMID- 8762779
TI  - Thickness extrema at the edge of astigmatic lenses including those with straight,
      circular and elliptical edges.
AB  - The problem of locating the points of maximum and minimum thickness at the edge
      of a lens, and of calculating the thickness at those points, is examined for lens
      powers and for edge shapes in general. The edge extremal problem, as the problem
      is called, is solved explicitly for general powers along straight cut edges. The
      extremal problem is also analysed for lenses with circular and elliptical edges
      but explicit solutions are obtained only for centrally cut lenses, that is,
      lenses with coincident optical and geometrical centres. For edges that are
      neither straight nor centrally cut ellipses (including circles), it appears that
      explicit solutions cannot be obtained for the edge extrema: one has to resort to
      numerical solution of implicit equations or to the calculation of thickness at
      sufficiently many points around the edge. For the centrally cut ellipse the edge
      extremal problem turns out to be the eigenvalue problem of linear algebra. In
      general the thickness extrema at the edge do not lie on the principal meridians
      of the lens, nor do they lie on meridians that are mutually perpendicular. With
      minor modification the results apply equally well to the edge extrema for sagitta
      of a surface.

PMID- 8762780
TI  - Clinical comparison of the Keeler Pulsair 2000, American Optical MkII and
      Goldmann applanation tonometers.
AB  - The aim of our study was to evaluate the performance of both the Keeler Pulsair
      2000 and the American Optical (AO) MkII non-contact tonometers (NCT) and compare
      these to the reference Goldmann standard using the same group of patients. Forty
      five patients (89 eyes) receiving medical treatment for primary open angle
      glaucoma had their intraocular pressure (IOP) measured with each instrument in a
      random order using five experienced observers. In the IOP range of the sample (6
      27 mmHg) the difference between means for each tonometer was small. The Pulsair
      2000 (mean = 19.06 mmHg, SD 6.28) read slightly higher than Goldmann (mean =
      18.01 mmHg, SD 4.88), whereas the AO MkII read slightly lower (mean = 16.27 mmHg,
      SD 5.93). However, all differences were statistically significant (P < 0.001,
      repeat measures ANOVA). Correlation coefficients for Pulsair 2000 versus Goldmann
      was r = 0.82 and for AO MkII versus Goldmann was r = 0.85. In addition, the
      repeatability for each NCT was assessed using 10 consecutive measurements on a
      further 10 subjects. The Pulsair 2000 showed significantly greater variation of
      IOP (mean SD 3.43 mmHg) than the AO MkII (mean SD 1.76 mmHg), confirming the need
      for taking at least four readings per eye with the Pulsair 2000. These variations
      are greater than that generally observed with Goldmann, and possible explanations
      why this occurs are discussed. In conclusion, subject to these limitations, both
      NCTs should be useful for measuring IOP as part of a screening protocol for
      glaucoma.

PMID- 8762781
TI  - Visual evoked potentials in children with developmental coordination disorder.
AB  - Children who demonstrate problems with skilled movement in the absence of
      physical handicap are formally designated as suffering from developmental
      coordination disorder (DCD). Diagnosis of DCD was confirmed by the 'movement
      assessment battery for children'. Visually evoked potentials (VEPs) were recorded
      to evaluate the integrity of the visual pathway and to rule out the presence of
      any neurological lesions affecting visual input. Binocular, pattern onset VEPs
      were recorded in 14 children with DCD aged between five and seven years, and an
      age-matched control group using pattern onset, high contrast, grating stimuli.
      Implicit times to the first and second peaks and troughs were measured, and
      results between the two groups were compared. Inattention and movement artefact
      meant that VEPs were more difficult to record within the DCD group, resulting in
      smaller amplitudes of the waveform, but no significant differences in the
      implicit times were observed between the DCD group and controls. Further research
      is required to determine the specific source of the neurological deficits in DCD
      but a problem with the integrity of the afferent visual pathway does not appear
      to be a causal factor.

PMID- 8762782
TI  - The exact solution for the centre thickness of spectacle and contact lenses.
AB  - The available methods for the exact calculation of centre thickness presuppose
      that one knows simultaneously both surfaces of the lens and that the lens' power
      is determined afterwards. However, this approach is of secondary importance in
      practical situations. The issue in daily practice is the determination of the
      centre thickness of lenses that already have explicit vertex powers. In such
      cases one can set only one surface. The other has to be calculated following the
      prescription, the known surface and the optical effect of the centre thickness.
      Exact solution for this problem leads to four expressions, reflecting the number
      of ways one can treat it. Two of them are complete second-order algebraic
      equations and the other two, complete third-order algebraic equations. The
      practical value of the latter is limited by the fact that one cannot always
      obtain their three roots by pure algebraic procedures.

PMID- 8762783
TI  - Nails--to ream or not to ream: developments and indications.

PMID- 8762784
TI  - Unreamed intramedullary nailing of femoral shaft fractures: operative technique
      and early clinical experience with the standard locking option.
AB  - Nailing techniques have changed in recent years in ways which are not just
      limited to omitting the reaming process. These changes concern positioning
      patients, techniques of reduction and selecting implants. Techniques of approach
      and exposure have been modified to new, less-invasive procedures to fulfill
      technical, functional and cosmetic requirements. In addition, techniques have
      been developed to avoid fragment diastasis, rotational and sagittal malalignment,
      and leg-length discrepancy. Finally, simple algorithms have been elaborated for
      the management of specific fracture patterns (bilateral shaft fractures,
      ipsilateral tibial fractures or associated femoral neck fractures) and to
      determine the number and location of locking bolts. We developed these
      algorithms, techniques and procedures in a series of 133 femoral shafts, which
      were stabilized with the AO unreamed femoral nail (URFN) in a prospective study
      between 1991 and 1994. Of these, the first 57 cases with a mean follow-up of 17.9
      months (range, 5-44) after injury were reviewed. Fractures were classified
      according to Muller's 1990 system: 12 type A, 29 type B and 16 type C. Closed
      soft-tissue injuries were classified by our classification of 1982: 17 type C
      0/I, 42 type C II. Of 15 open fractures, six were OI, six OII, two OIIIA and one
      was OIIIB by Gustilo's classification of 1984. The major complications were two
      broken locking bolts, one nail breaking after 9 weeks, one case of osteitis and
      one of intra-operative lung embolism.

PMID- 8762785
TI  - Unreamed nailing of tibial shaft fractures in multiply injured patients.
AB  - In a prospective study, 63 tibial shaft fractures were managed by intramedullary
      nailing with a solid nail inserted without reaming. The patients were followed to
      union or a definitive outcome (non-union or death). Three patients died early in
      the post operative course as a result of other injuries. This left 60 nails in
      the series for complete follow up. Eighty-two per cent of the fractures were the
      result of motor vehicle accidents, 44 nails were inserted within 72 h of injury.
      Fifty-six fractures united (93%) at a mean of 21.1 weeks (8-52). There were 4 non
      unions among this population of multiply injured patients. All closed fractures
      united at a mean of 19.5 weeks. Those nailed acutely united at a mean of 16.8
      weeks. The open fracture group (classified according to Gustilo and Anderson)
      included the 4 non-unions (2 type II, 1 type IIIa and 1 type IIIb). A union rate
      of 86.2% was achieved in these fractures. All type I fractures united. One deep
      infection occurred in the series. The major complication identified in the
      current series was failure of the distal cross bolts.

PMID- 8762786
TI  - The AO unreamed nail: friend or foe.
AB  - Twenty-nine tibial shaft fractures were stabilized with the AO unreamed tibial
      nail. These included 13 type A fractures, 11 type B fractures and five type C
      injuries. Fourteen of the fractures were open. The AO unreamed tibial nail was
      the primary device used in all cases. Our series suggests that this is an easy
      device to insert and that its multiple locking options confer an advantage for
      the management of distal fractures. It also has a low soft-tissue complication
      rate. There was a delay in full patient mobilization and in the progression to
      fracture union. There was also a significant degree of implant failure with screw
      breakage in 21 per cent. This necessitated a high rate of secondary operative
      intervention. The high incidence (55 per cent) of anterior knee pain was also
      worrying and frequently necessitated nail removal. We feel that this implant may
      still have a role for distal fractures and in the multiply injured patient but do
      not feel that, in its current form, it is the ideal implant for the majority of
      tibial shaft fractures.

PMID- 8762787
TI  - Unreamed intramedullary tibial nailing--fatigue of locking bolts.
AB  - Between January 1990 and October 1993 we investigated 72 consecutive patients who
      had an unreamed tibial nail inserted for fractures of the tibial shaft; 75 per
      cent (N = 54) were closed fractures and 25 per cent (N = 18) were open fractures.
      The mean follow up was 15.2 months. Of the patients 91.7 per cent (N = 66) were
      interlocked, 58 per cent (N = 38) statically and 42 per cent (N = 28)
      dynamically. Union rate was 98.6 per cent, time to union was 18.5 weeks, 17.3
      weeks for closed fractures, 22 weeks for open fractures. Shortening greater than
      1 cm occurred in 1.4 per cent (N = 1), varus and valgus deformity in 4.1 per cent
      each (N = 3). There was no rotational deformity. Of the locking bolts 30 per cent
      broke 8-10 weeks after partial weight bearing was allowed. Electron microscopy
      investigations showed that failure of the bolts was due to fatigue. It was not
      associated with any clinical problems with regard to union times or incidence of
      malunion. Bolt failure is however a problem if you try to remove the nail.

PMID- 8762788
TI  - A comparison of one versus two distal locking screws in tibial fractures treated
      with unreamed tibial nails: a prospective randomized clinical trial.
AB  - The objective was to determine whether the number of interlocking screws have an
      impact on hardware failure. In a clinical prospective randomized study of
      skeletally mature patients with diaphyseal tibial fractures, 44 were randomized
      pre-operatively into the two treatment arms over a two-year period. Two patients,
      one from each group, were excluded later. Of eligible patients, 22 had one distal
      locking screw and 20 had two distal locking screws. One distal screw failed (59.1
      per cent) significantly more often than two distal screws (5 per cent). Screw
      failure occurred more often in heavier patients and usually between six and 12
      weeks. Proximal screw failure was seen in 17 per cent of patients. There was no
      significant difference between groups with respect to fracture union.

PMID- 8762789
TI  - Penicillin prophylaxis in complicated wounds of hands and feet: a randomized,
      double-blind trial.
AB  - The purpose of the study was to examine the effect of prophylactic penicillin
      treatment on the infection rate in patients with traumatic wounds of hands or
      feet with underlying lesions of bone, tendon or joint. A total of 599 patients
      were randomized to double-blind treatment with either (A) one injection of
      penicillin G, (B) penicillin V tablets for 6 days or (C) no antibiotic treatment.
      In group A the infection rate was 4.9 per cent, in group B 6.7 per cent and in
      group C 10.2 per cent. The difference between the infection rates in group A and
      C was 5.3 per cent with a 95 per cent confidence interval (CI) from 0.1 to 10.4
      per cent (P = 0.046). Correction for an interim analysis and subgroup analyses
      increases this P value to 0.096. The difference between the infection rates in
      group B and C was 3.6 per cent (95 per cent CI from -1.9 to 8.9, P = 0.20).
      Patients in group B had gastrointestinal complaints five times as often as
      patients in group A and C. Prophylactic tablets for 6 days require patients' co
      operation while an injection ensures that the prophylaxis is given. We therefore
      conclude that a single prophylactic injection of two million units of penicillin
      G is advisable for patients with these injuries.

PMID- 8762790
TI  - A prospective study of 924 digital fractures of the hand.
AB  - A prospective study of 1129 patients with 1358 digital fractures of the hand was
      carried out between March 1984 and March 1994; of these, 924 fulfilled the
      criteria for inclusion. Functionally stable fractures with acceptable alignment
      were managed with immediate active mobilization. Unstable fractures, or fractures
      with unacceptable alignment, were openly reduced and fixed internally so that
      active mobilization could begin immediately after operation. The function results
      using various systems of evaluation were excellent or good in over 90 per cent of
      the fractured thumbs, and excellent or good in 58.7 per cent to 76.5 per cent of
      the fingers. Patients who did not require surgery did much better than those in
      the operated group. Comminuted, open and multiple fractures proved to be of poor
      prognostic value. However, rigid fixation was statistically significant in
      influencing the outcome.

PMID- 8762792
TI  - Clostridial septic shock following an isolated, hepatic gunshot wound.

PMID- 8762791
TI  - Fracture of the femoral neck: optimal screw position and bone density determined
      by computer tomography.
AB  - The bone density of five proximal femurs from female cadavers was measured with
      computed tomography using a pixel size of 1.2 mm. A three dimensional
      reconstruction was performed along four well-defined axes. The region of maximal
      relative bone density correlated well with a previous report of the optimal
      position of a screw when treating a fracture of the femoral neck.

PMID- 8762793
TI  - Novel method for removal of a broken GK femoral nail.

PMID- 8762794
TI  - New guidance on general anaesthesia, resuscitation and sedation.

PMID- 8762795
TI  - Conflicting advice.

PMID- 8762796
TI  - More tooth wear.

PMID- 8762797
TI  - Burning mouth syndrome.

PMID- 8762798
TI  - What is private practice?

PMID- 8762799
TI  - British pioneer?

PMID- 8762800
TI  - Post dentine bonding sensitivity.

PMID- 8762801
TI  - Persistent haemorrhage following dental extractions in patients with liver
      disease.

PMID- 8762802
TI  - Controlling dental occupational exposure to nitrous oxide.

PMID- 8762803
TI  - A survey of the effectiveness of dental light-curing units and a comparison of
      light testing devices.
AB  - The aims of this study were to: 1. survey the light output from 49 light-curing
      units in clinical use; 2. measure the effect on depth of cure of composite resin
      caused by a range of light outputs; 3. assess the relationship between radiometer
      meter readings and depth of cure of composite resin in a human tooth model and a
      Heliotest. The mean meter reading produced by the 49 lights surveyed using a
      lampChecker radiometer was 4.4 (+/-2.4 SD), range 0.3 to 10.0. The manufacturer
      of the radiometer considers optimal light output to provide a meter reading
      within the range 5.0 to 7.0. Lights of very low output (0.7 +/- 0.1 SD) were
      found to be capable of curing, after 20 seconds, a 1.9 (+/-0.3 SD) mm thickness
      of composite resin. However, only approximately 50% of this thickness can be
      considered fully cured. Increasing the cure time from 20 seconds to 60 seconds
      increased the mean depths of cure by a factor of approximately 1.4. The mean
      depths of cure of composite resin placed in the Heliotest were greater than those
      observed in the natural tooth model, by a factor of approximately 1.3.
      Correlation coefficients of meter readings and depth of cure were greater for the
      Efos Cure Rite and Demetron 100 radiometers than the lampChecker unit.

PMID- 8762804
TI  - Response to intravenous midazolam sedation in general dental practice.
AB  - The object of this study was to grade the response of patients undergoing a
      variety of dental procedures with the aid of intravenous midazolam sedation in
      general dental practice and to explore any relationships between the patients
      preoperative anxiety assessment and the clinician's assessment of co-operation
      whilst under sedation. One hundred consecutive patients aged between 18 and 58
      years (mean 32 years; sd 10 years) and in ASA Class I or II were prospectively
      studied. Results showed that despite attempts to grade patient's behaviour it was
      not possible to reliably predict patient's responses under intravenous sedation.
      In addition to these findings, the great individual variation in sensitivity to
      midazolam was confirmed.

PMID- 8762805
TI  - Bulimia: implications for the practising dentist.
AB  - The incidence of eating disorders appears to be increasing, with the dental
      practitioner potentially being the first healthcare worker to make a diagnosis,
      due to the characteristic dental signs of tooth substance loss. It is therefore
      important that members of the dental team are aware of the dental sequelae of
      anorexia and bulimia and are able to offer advice and treatment to sufferers.

PMID- 8762806
TI  - Practical marketing for dentistry. 2. The core concepts of marketing.
AB  - This series identifies the ideas and concepts behind modern marketing thinking,
      and suggests areas for consideration when creating a marketing 'culture' within
      general dental practices, dental supplies businesses, service suppliers,
      laboratories-or indeed any organisation which wants to succeed in today's
      challenging conditions.

PMID- 8762807
TI  - Caught in the web.
AB  - The web is an exciting medium and if carefully used can provide a wealth of
      information; the sites described in this article are useful starting points.
      However, the process of getting the information down the telephone line can be
      time consuming. The collection of pictures for this article, for example, took
      one hour of surfing the web. However, such activity is fun, educational and when
      started becomes addictive.

PMID- 8762808
TI  - Congenital absence of permanent second molars.
AB  - During the last eight years, Canterbury Archaeological Trust has excavated over
      1,600 articulated human skeletons from sites under threat of redevelopment in
      Kent. The recovered material, ranging in date from prehistoric to Victorian,
      provides a unique corpus for the study of disease and abnormalities in earlier
      societies.

PMID- 8762809
TI  - HIV-1-associated pathology in hemato-lymphoid organs and the experimental
      evaluation in the SCID-hu mouse.
AB  - A variety of possible mechanisms for the loss of CD4+ T cells has been proposed,
      such as direct cytopathic effects by HIV-1 infection, and indirect induction of
      apoptosis. However, the fundamental picture of major and central pathogenic
      processes for the decay of immune systems is still missing in understanding the
      pathogenic mechanisms of HIV-1 infected humans. It is more appropriate to expand
      our focus onto entire organ systems involved in the development of immune system
      such as bone marrow and thymus. From the observations in the clinical studies,
      HIV-1 causes a variety of pathology on the T cell development pathway even from
      the hematopoietic progenitors and immature thymocytes, which should have a
      substantial impact on the failure of T cell homeostasis in the periphery. The
      SCID-hu mouse constructed by surgical implantation of human fetal hemato-lymphoid
      organs into the immunodeficient mouse has been used for the experimental
      evaluation of various parameters associated with HIV-1 infection and
      hematosuppression. Given the apparently normal structure and function of the
      human implants, the SCID-hu bone and Thy/Liv mice would appear to be potentially
      reliable models for the analysis of human physiology and patho-physiology.

PMID- 8762810
TI  - Novel insights into the biology of myelodysplastic syndromes: excessive apoptosis
      and the role of cytokines.
AB  - The paradox of myelodysplastic syndromes (MDS) which present with pancytopenias
      despite cellular bone marrows (BM) was investigated by conducting detailed
      studies of proliferation and apoptosis in 89 MDS patients. Our results
      demonstrated a rapid rate of both proliferation as well as apoptosis. Levels of
      three cytokines, tumor necrosis factor-alpha (TNF-alpha), transforming growth
      factor-beta (TGF-beta) and interleukin-1 beta (IL-1 beta) were measured in the
      same patients. High levels of TNF-alpha were found to correlate with high levels
      of apoptosis in 83 MDS patients (P = 0.0045). We propose a dual role for TNF
      alpha (or other cytokines) in the pathogenesis of MDS. On the one hand, TNF-alpha
      induces apoptosis in the maturing cells causing pancytopenia while on the other,
      it stimulates the proliferation of the primitive progenitors accounting for the
      hypercellular BM frequently seen in MDS. A new model for MDS is presented. The
      initial abnormality probably affects a primitive hemopoietic progenitor which
      acquires a growth advantage leading to monoclonal hemopoiesis, which in turn
      makes these cells susceptible towards acquiring additional mutations and
      appearance of cytogenetically marked (or unmarked) clones. Cytokines such as TNF
      alpha whose source is presently unknown, then contribute towards the clinical
      syndrome of pancytopenia and hypercellularity.

PMID- 8762811
TI  - Lymphoproliferative disorders of natural killer cells.
AB  - Natural killer (NK) cells are a distinct non-T, non-B lineage of lymphocytes that
      mediate major histocompatibility complex-unrestricted cytotoxicity.
      Morphologically they are large granular lymphocytes, and phenotypically they
      commonly express CD16 and CD56 antigens, without expressing cell surface CD3.
      Although the developmental pathway of NK cells is not fully understood, they
      arise from CD34+ hematopoietic stem cells and, at least in part, differentiate in
      the bone marrow. They gain byctoplasmic CD3 gamma delta epsilon zeta antigens
      during maturation, and lose cytoplasmic CD3 gamma delta epsilon thereafter until
      the terminal maturation. Lymphoproliferative disorders of NK cells include NK
      cell-lineage granular lymphocyte-proliferative disorders (NK-GLPD), NK-cell
      lymphoma, and acute leukemia of NK-cell lineage. NK-GLPD are relatively rare.
      Most patients exhibit a chronic indolent clinical course, and do not require
      specific treatment. However, some patients exhibit an aggressive clinical course,
      and die of the disease despite extensive chemotherapy. This aggressive type NK
      GLPD is caused by Epstein-Barr virus (EBV). Patients with NK-cell lymphoma are
      rare, and often exhibit necrotic lesion and angiocentric morphology. This tumor
      is mainly found in the nasal tract, but the true incidence of NK-cell lymphoma in
      nasal lymphomas is not known. Probably many lymphomas arising from the nasal
      cavity, but not from paranasal sinuses, are of NK-cell lineage. NK-cell lymphoma
      is also caused by EBV, and is resistant to combination chemotherapy. Acute
      leukemia of NK-cell lineage is very rare. Several cases of acute lymphoblastic
      leukemia and a single case of blast crisis of chronic myelogenous leukemia have
      been documented to have leukemic blasts characteristic of NK cells. However, the
      precise lineage and differentiation stage of the leukemic blasts have not been
      delineated.

PMID- 8762812
TI  - In vivo effects of various therapies on complement-sensitive erythrocytes in
      paroxysmal nocturnal hemoglobinuria.
AB  - The percentage of complement-sensitive erythrocytes varies among patients with
      paroxysmal nocturnal hemoglobinuria (PNH) and is related to disease severity. We
      examined the changes of complement-sensitive erythrocytes following
      administration of androgens, prednisolone, dextran, and iron to 12 PNH patients
      using the complement lysis sensitivity test or flow cytometric analysis of decay
      accelerating factor and CD59/membrane attack complex-inhibitory factor expression
      for 11 years. Five untreated PNH patients were also studied as a control group.
      The complement-sensitive erythrocyte count remained almost constant in the
      control group, while it increased in four out of five patients receiving
      androgens. In addition, it decreased in two out of three patients receiving
      prednisolone, increased in both patients treated with dextran, and increased
      slightly in two of the three patients receiving iron therapy. Episodes of
      hemoglobinuria increased in three of the nine patients showing an increase of
      complement-sensitive erythrocytes, and decreased in four patients receiving
      prednisolone or dextran. A good response to treatment was clinically observed in
      four patients receiving androgens, in one patient treated with prednisolone, and
      in one patient receiving dextran according to the scoring system. These findings
      suggest that PNH remains stable when the number of complement-sensitive
      erythrocytes remains fairly constant, and that the PNH III erythrocyte count is
      especially related to the frequency of hemoglobinuria. Thus, it seems to be
      important to determine the long-term effect of drug therapy on complement
      sensitive erythrocytes to select the most appropriate treatment.

PMID- 8762813
TI  - Regulation of egr-1 gene expression by retinoic acid in a human growth factor
      dependent cell line.
AB  - Retinoic acid (RA) has profound suppressive effects on growth and survival of
      human growth factor-dependent cell line, M07e. Treatment of M07e cells by RA
      reduced expression of egr-1 gene, while the levels of c-myc gene expression
      remained similar. Suppression of egr-1 gene expression by RA was dosage-dependent
      and reached maximum at 4 h after RA addition. The decay of egr-1 mRNA was similar
      in M07e cells treated with or without RA. The transcriptional activity of the
      promoter region up to -600 or -480 bp upstream of the egr-1 gene was greatly
      reduced by RA treatment. These data suggest that biological effects of RA on
      hematopoietic cells may, in part, be mediated by transcriptional suppression of
      egr-1 gene through its promoter region within -480 bp.

PMID- 8762814
TI  - Effects of granulocyte colony-stimulating factor on the hemostatic system in
      healthy volunteers.
AB  - We previously identified a receptor for granulocyte colony-stimulating factor (G
      CSFR) on platelet membranes, and reported that G-CSF enhanced ADP-induced
      platelet aggregation. Here, we investigated the priming effect of G-CSF on the
      hemostatic system in healthy volunteers given G-CSF. Following the administration
      of rhG-CSF (10 micrograms/kg for 30 min div) to 10 healthy volunteers, we found a
      significant elevation in the maximum platelet aggregation rate induced by ADP or
      collagen, thromboxane B2 level and amount of thrombin-antithrombin III complex.
      The D-D dimer and plasminogen activator inhibitor-1 showed no significant
      changes. These observations indicate that G-CSF administration may induce
      hypercoagulability in susceptible subjects. Therefore, patients or donors at risk
      of thrombosis or hypercoagulable state should be followed carefully after G-CSF
      administration.

PMID- 8762815
TI  - Vascular thromboxane formation in hemostasis mechanism: correlation between
      bleeding time and vascular TXB2 in a patient with congenital platelet cyclo
      oxygenase deficiency.
AB  - We encountered a patient with congenital platelet cyclo-oxygenase deficiency with
      normal ability to synthesize vascular prostaglandin I2 (PGI2) and thromboxane A2
      (TXA2). The patient's peripheral blood monocytes did not show cyclo-oxygenase
      (COX) activity, but cultured bone marrow fibroblasts showed COX activity. To
      determine the mechanism of primary hemostasis in this patient, we examined the
      effect of oral administration of aspirin (1 g) on bleeding time and thromboxane
      B2 (TXB2), 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha) production in the
      blood emerging from the incision in this patient. The bleeding time was markedly
      prolonged by the administration of aspirin, and this prolongation was associated
      with the inhibition of TXB2 in the effluent blood, which seemed to be derived
      from the vessel wall. These findings suggest that vascular TXA2 production plays
      an important role in the maintenance of hemostasis.

PMID- 8762816
TI  - Primary meningeal lymphoma presenting solely with blindness: a report of an
      autopsy case.
AB  - A 64-year-old woman was admitted because of progressive paraplegia. She had a
      history of unexplained blindness which had developed gradually 1 year earlier.
      The contrast-enhanced CT showed a small mass at the sella turcica. The funduscopy
      showed merely atrophic discs. The lumbar puncture revealed marked pleocytosis
      (cell count: 10.4 x 10(9)/l) and a diagnosis of meningeal lymphoma was made by
      the cytology of the cerebrospinal fluid. No lymphomatous lesions were detected
      outside of the central nervous system (CNS) and the patient received whole brain
      irradiation together with intrathecal chemotherapy. However, there was no
      improvement in vision or other neurological activities. Eventually the patient
      died of interstitial pneumonia 2 months after admission. The autopsy revealed a
      residual B-cell lymphoma existing only in the leptomeninges of medulla oblongata.
      The optic nerves were atrophic macroscopically and massive gliosis was seen
      microscopically. In addition, cytomegalovirus infection was observed in the lungs
      and adrenal glands but not in the CNS. This patient must have had a primary
      meningeal lymphoma. The mechanism of the visual loss of this patient is
      discussed.

PMID- 8762817
TI  - [Effect of lomefloxacin on luminol-dependent chemiluminescence and adhesion of
      leukocytes].
AB  - The in vitro effect of lomefloxacin within the wide dose ranges from 0.1 to 100
      micrograms/ml on luminol-dependent chemiluminescence and adherence of
      polymorphonuclear leukocytes of guinea pigs was studied under two different
      conditions: during the cell incubation in the presence of various concentrations
      of the drug and after the cell washing to remove lomefloxacin. In concentrations
      of 10 and 100 micrograms/ml the drug inhibited the response under the both
      conditions while in a concentration of 1 microgram/ml it stimulated the
      chemiluminescence. In concentrations of 0.1 to 100 micrograms/ml lomefloxacin
      stimulated the leukocyte adherence. The highest stimulation was observed with the
      use of the drug in a concentration of 1 microgram/ml.

PMID- 8762818
TI  - [Effect of a peptide from the mollusk optical ganglia on macrophage functional
      activity].
AB  - Gangliin (tinrostim), a novel peptide isolated from the nervous tissue of the
      food mollusks, was investigated with respect to its effect on the cells of the
      system of the mononuclear phagocytes. It was shown to have a high protective
      action in some experimental infections. One of the main mechanisms of the
      gangliin action was the increase of the functional activity of the cells of the
      system of the mononuclear phagocytes. It was demonstrated that gangliin induced a
      decrease in the activity of 5'-nucleotidase and increased the absorption and
      digestive functions of the macrophage.

PMID- 8762819
TI  - [Various indices of the infectious process in treatment of glanders in monkeys].
AB  - The time course of the clinical, biochemical and serological indices was studied
      during the treatment of malleus in monkeys. The internal organs of the animals
      infected with Pseudomonas mallei were investigated pathomorphologically. The
      efficacy of the biseptol/oxalinic acid combination in the therapy of malleus was
      estimated.

PMID- 8762820
TI  - [Comparative study of the antimicrobial activity of pefloxacin, ciprofloxacin,
      norfloxacin and azithromycin with respect to Strains of Yersinia
      pseudotuberculosis].
AB  - Ciprofloxacin (C), pefloxacin (P) and norfloxacin (N) had a marked effect on
      Yersinia pseudotuberculosis strains isolated from the infected humans and
      animals. The activity of C (MIC 0.0312-0.125 microgram/ml) was higher than that
      of P and N (MIC 0.0625-2.0 micrograms/ml). The isolates were resistant to
      azithromycin (MIC 3.1-100 micrograms/ml). The susceptibility of the strains did
      not depend on the source of their isolation. The polyresistant strains carrying
      the R plasmids preserved the susceptibility to the fluoroquinolones.

PMID- 8762821
TI  - [Antibioticograms of microorganisms isolated from foci of local infections in
      infants].
AB  - Microbiological tests were performed in regard to 474 newborns within 1985-1995.
      It was shown that gram-positive microflora (Staphylococcus epidermidis and
      Staphylococcus aureus) predominated in the etiological structure of omphalitis
      and conjunctivitis. Among gram-negative isolates in the cases with omphalitis
      there predominated Klebsiella pneumonia. The antibioticograms were of great
      practical value for the adequate therapy.

PMID- 8762822
TI  - [Cefpirome-- a new 4th generation cephalosporin antibiotic].

PMID- 8762823
TI  - [Bacterial beta-lactamases].

PMID- 8762824
TI  - Approach for the smoothing of three-dimensional reconstructions of the human
      spine using dual Kriging interpolation.
AB  - In numerous situations, 3-D reconstructions of the spine are represented as
      curves in space, with the vertebral centroids as control points. Interpolation
      functions such as splines, polynomials or Fourier series have been used to
      minimise measurement errors and to perform specific calculations. A more general
      approach, dual Kriging, is presented which incorporates in a single formulation
      several methods, such as piece-wise linear interpolation, splines and least
      square functions as a limit case. To minimise user interaction and to control the
      different Kriging parameters, a computer program is developed allowing efficient
      use of these interpolation techniques in a clinical environment. Given different
      drift and covariance functions, the program determines the most suitable Kriging
      model for specific spine geometries and controls the amount of smoothing
      performed on raw data. Validation of the technique is with analytical 3-D curves,
      where random noise is added to represent reconstruction errors. A maximum
      absolute mean difference of 1.85 +/- 0.50 mm is found between the analytical and
      noisy curves smoothed with the Kriging technique for 200 points. Results obtained
      on actual 3-D reconstructions of scoliotic patients are very promising.

PMID- 8762825
TI  - In vivo validation of a fluid dynamics model of mitral valve M-mode
      echocardiogram.
AB  - A fluid dynamics model of mitral valve motion during diastolic filling of the
      left heart is described. Given a pulsed Doppler velocity pattern in the mitral
      annulus, the radius of circular mitral orifice, the length of leaflets and the
      end-systolic left ventricular volume, the numerical model predicts the time
      course of the mitral leaflets during diastole: the mitral valve M-mode
      echocardiogram. Results obtained by computer simulation have been validated with
      in vivo data. It is shown that mitral valve flow is essentially a fluid dynamics
      process of floating mitral valve leaflets with blood flow due to the
      atrioventricular pressure gradient. In addition, a partial opening of the mitral
      valve as the initial boundary condition is required to simulate the overshooting
      of the leaflets during early peak filling. Some back flow is a condition for
      perfect closing of the native mitral valve. The higher the unsteady character of
      mitral flow, the less efficient is the opening and closing processes of the
      mitral valve.

PMID- 8762826
TI  - Multivariate autoregressive model with immediate transfer paths for assessment of
      interactions between cardiopulmonary variability signals.
AB  - Multivariate autoregressive modelling provides a method to analyse the dynamic
      interactions between heart rate (HR), blood pressure (BP) and respiration (RESP)
      by means of noise source contributions (NSCs). The conventional approach presumes
      the modelled noise sources are mutually independent. This presumption is, in
      general, not satisfied and causes an error in the results. In the present study,
      the effect of this error is analysed. A method is presented to remove the error
      by making the noise sources independent. The method is based on the inclusion of
      immediate transfer paths in the model. To quantify the strength of the
      interactions, a measure called NSC ratio (NSCR); is calculated; this states the
      amount of variability of the signal arising from other signals. The method is
      demonstrated by studying the inter-relationships between HR, BP and RESP in a
      healthy male subject in supine and standing positions. It is found that the error
      is marked and that the presented method provides corrected estimates for spectral
      decomposition and NSC analysis. The results show it is necessary to include the
      immediate transfer mechanisms in the model, while analysing the cardiopulmonary
      dynamics by means of HR and BP variability.

PMID- 8762827
TI  - Chamber for indirect calorimetry with improved transient response.
AB  - A chamber for indirect calorimetry has been constructed that utilises previously
      published general equations for the calculation of respiration. Owing to the
      large size of the chamber, the changes in gas concentration caused by a subject
      are very small. Therefore, algorithms are developed for noise suppression and
      trend identification. Using the exact solution of the equations for steady state,
      each gas concentration is fitted by a least square method to two connected
      exponential segments, of variable length, for the preceding 30 min period.
      Independently of the location of the join between the two segments, the gas
      concentration and its time derivative are evaluated at -15 min. This process is
      repeated, and its results are presented once every minute. As proven by gas
      injection tests, this procedure gives an instantaneous response to a single
      change in respiration, a correct averaging of repeated changes in respiration
      with periods of less than 15 min and noise suppression. It is concluded that this
      chamber is useful not only for traditional 24 h energy expenditure measurements,
      but also for experiments requiring rapid responses.

PMID- 8762828
TI  - Electromagnetic pulse distortion in living tissue.
AB  - Insight into the distortion of electromagnetic (EM) signals in living tissue is
      important for optimising medical applications. To obtain this insight, field
      calculations have been carried out for a plane-stratified configuration of air,
      skin, fat, muscle and bone tissue. In this configuration, an EM field is
      generated by a prescribed pulsed current in a circular loop. Debye dispersion
      models have been developed for the description of the permittivity of the
      tissues. The field problem is solved analytically with the aid of a temporal
      Fourier transformation and a spatial Hankel transformation. The corresponding
      inverse transformations have been carried out numerically. To demonstrate the
      influences of stratification and dispersion separately, the EM fields in the
      stratified configuration, in a completely muscle-filled space and in vacuum are
      compared. Two different pulses have been considered; narrow and wide. It emerges
      that dispersion results in a retardation and an attenuation of the field.
      Stratification causes additional fluctuations of the time-dependent field.
      Furthermore, the conductivity of tissue at high frequencies is mainly determined
      by its water content. Tissues with high water content, like muscle and skin,
      exhibit higher conductivity at high frequencies than fat and bone. Muscle and
      skin tissue therefore behave as low-pass filters to EM signals.

PMID- 8762829
TI  - Optimising the methodology of calculating the cerebral blood flow of newborn
      infants from near infra-red spectrophotometry data.
AB  - Cerebral blood flow can be measured in neonates by near infra-red
      spectrophotometry. The tracer is oxyhaemoglobin. The purpose of the study is to
      compare the test-retest variability of two previously proposed methods (UCH and
      COP) of analysis, and to investigate the influence of sampling rates, smoothing
      and integration periods. Under clinical conditions good measurements are often
      difficult to obtain. Therefore, a second goal is to find ways of determining the
      quality of individual measurements. 380 cerebral blood flow measurements from 69
      infants are analysed. The data set is optimised statistically for the lowest test
      retest variability and the following results are obtained. The test-retest
      variability of measurements at 2 s sampling time data is considerably worse than
      at 0.5 s sampling time. Smoothing does not change the test retest variability. A
      6 s integration period gives higher values and higher test-retest variability
      than an 8 s integration period. By applying the suggested criteria, a test-retest
      variability of 17% is achieved, if 50% of the measurements are rejected. The mean
      cerebral blood flow is 12.2 ml (100 g)-1 min-1 for the UCH method and 9.7 ml
      [corrected] (100 g)-1 min-1 for the COP method. The test-retest variability of
      both methods is comparable for 0.5 s sampling time. For 2 s sampling time the
      method proposed by Skov et al. is significantly better. These test retest
      variabilities represent maximum values, part of the observed variability may be
      due to physiological changes of unknown magnitude.

PMID- 8762830
TI  - Evaluation of laser Doppler imaging to measure blood flow in knee ligaments of
      adult rabbits.
AB  - Laser Doppler imaging (LDI) is investigated as a novel method for in vivo
      ligament tissue blood flow determination. LDI output signal is obtained from
      surgically exposed rabbit medial collateral ligaments (MCL). The LDI signal is
      compared with simultaneously determined, coloured microsphere (CM)-derived
      standardised MCL blood flow. Correlation of LDI output with the CM flow data and
      a linear regression of 17 data points in nine rabbits (joint injured to provoke
      an acute vascular response in the tissues) indicate that LDI provides a
      reasonable estimate of MCL blood flow, at least over the ranges assessed. If
      properly calibrated, and given enough tissue-specific data points, LDI may have
      advantages over conventional, but more invasive, techniques. The potential
      clinical application of LDI technology to joint injury and arthritis research is
      discussed.

PMID- 8762831
TI  - Dependence of coherence measurements on EEG derivation type.
AB  - The impact is reported of different EEG derivation types on short-term changes in
      the inter-hemispheric coherence between the left and right sensorimotor areas,
      during the planning and execution of right index finger movements. Data are
      recorded during an event-related paradigm in which cued index finger movements
      are made: Event-related coherence analysis is then applied to the monopolar (nose
      reference) data, as well as different reference-independent derivations such as
      bipolar, local average reference and source derivation. The results show that
      inter-hemispheric coherence between sensorimotor areas is dependent on the EEG
      derivation type. An increase in coherence during movement is found with nose
      reference and bipolar data, whereas for local average reference and source
      derivations, low inter-hemispheric coherence is observed, with no change in the
      coherence during movement. It is concluded that the coherence increase seen with
      nose reference data is due to an indirect effect of mu rhythm desynchronisation,
      rather than any increase in synchrony of the mu rhythms themselves. Local average
      reference and source derivations better reflect the activity of the underlying
      cortical structures (the mu generating networks), and coherence analysis using
      these derivations shows that the mu rhythms of left and right hemispheres are not
      coherent.

PMID- 8762832
TI  - Two-dimensional spectral processing of sequential evoked potentials.
AB  - The processing of sequential evoked potentials (EPs) is investigated using two
      dimensional processing techniques. Two-dimensional EP arrays or images are formed
      by stacking sequential recordings. Processing is accomplished in the frequency
      domain by 2-D low-pass filtering using Gaussian filters. Auditory brainstem
      responses (ABRs), which are the early auditory EPs, are used to investigate the
      effects of the 2-D filtering on real data. Gaussian filtering improves signal-to
      noise ratios by reducing high frequency noise effectively in both intra-EP and
      inter-EP dimensions. Applications to intra-operative monitoring are simulated
      with real ABR data.

PMID- 8762833
TI  - Extracting quantitative information from digital electrogastrograms.
AB  - Cutaneous recordings of gastric electrical activity (electrogastrography (EGG))
      could become a valuable non-invasive tool for recognising gastric electrical
      abnormalities. Although signals obtained with internally implanted electrodes
      deliver quantitative information, this technique cannot be used for diagnostic
      purposes because of its invasive nature. On the other hand, the objectivity of
      electrogastrography is still in question. The aims of this work are to develop
      computer techniques for extracting quantitative information from digital
      electrogastrograms, and to evaluate quantitatively EGG recordings from healthy
      volunteers. The dynamics of all four EGG parameters are studied: amplitude,
      frequency, time shift between different channels, and waveform. Four separate two
      dimensional computer plots are developed using specially designed digital signal
      processing procedures. Each parameter is evaluated in a study of 20 healthy
      volunteers. Frequency is found to be the only EGG parameter that shows
      quantitative consistency and merit.

PMID- 8762834
TI  - Three-dimensional kinematic technique for evaluation of horse locomotion in
      outdoor conditions.

PMID- 8762835
TI  - In vivo EIT electrode system with 32 interlaced active electrodes.

PMID- 8762836
TI  - Concurrent computing for picture archiving and communication system.

PMID- 8762837
TI  - Anastomotic vortex generator.

PMID- 8762838
TI  - Vulval algesiometer.

PMID- 8762839
TI  - Impact of external factors on the stability of human electrogastrograms.

PMID- 8762840
TI  - Directly-observed therapy, patient education and combined drug formulations:
      complementary, not alternative, strategies in tuberculosis control.

PMID- 8762841
TI  - What's in a name ... TB or not TB?

PMID- 8762842
TI  - The zoonotic importance of Mycobacterium bovis.
AB  - The zoonotic importance of Mycobacterium bovis has been the subject of renewed
      interest in the wake of the increasing incidence of tuberculosis in the human
      population. This paper considers some of the conditions under which transmission
      of M. bovis from animals to humans occurs and reviews current information on the
      global distribution of the disease. The paper highlights the particular threat
      posed by this zoonotic disease in developing countries and lists the veterinary
      and human public health measures that need to be adopted if the disease is to be
      contained. The association of tuberculosis with malnutrition and poverty has long
      been recognized and the need to address these basic issues are as crucial as
      specific measures against the disease itself.

PMID- 8762843
TI  - Rebuttal: time to call a halt to emotions in the assessment of thioacetazone.

PMID- 8762844
TI  - Cigarette smoking as a risk factor for tuberculosis in young adults: a case
      control study.
AB  - SETTING: The association between smoking and pulmonary tuberculosis has not often
      been studied. OBJECTIVE: To assess the influence of cigarette smoking on the
      development of active pulmonary tuberculosis in young people who were close
      contacts of new cases of smear-positive pulmonary tuberculosis. DESIGN: A case
      control study in which 46 'cases' (patients with active pulmonary tuberculosis:
      isolation of Mycobacterium tuberculosis or clinical and/or radiographic evidence
      of current pulmonary tuberculosis, with a positive tuberculin skin test) and 46
      'controls' (persons with positive tuberculin reaction, negative bacteriological
      test and without clinical and/or radiological evidence of pulmonary tuberculosis)
      were included. Smoking habits were investigated by questionnaire. Univariate and
      multivariate analysis was performed, and odds ratio (OR) was adjusted for age,
      gender and socio-economic status. RESULTS: Statistically significant differences
      were found in active smokers (occasional and daily smokers) (OR: 3.65; 95% CI,
      1.46 and 9.21; P < 0.01), daily smokers (OR: 3.53; 95% CI, 1.34 and 9.26; P <
      0.05), and individuals who were both passive and active smokers (OR: 5.10; 95%
      CI, 1.97 and 13.22; P < 0.01) and passive and daily smokers (OR: 5.59; 95% CI,
      2.07 and 15.10; P < 0.001). There was a dose-response relationship between the
      number of cigarettes smoked daily and the risk of active pulmonary tuberculosis.
      CONCLUSIONS: The data studied show that cigarette smoking is a risk factor for
      pulmonary tuberculosis in young people, with a dose-response relationship with
      the number of cigarettes consumed daily.

PMID- 8762846
TI  - Sputum smear conversion during directly observed treatment for tuberculosis.
AB  - SETTING: Treatment program for tuberculosis in a refugee camp in Thailand.
      OBJECTIVES: To determine the cumulative frequency of conversion of sputum smears
      examined by direct microscopy by month of treatment and to identify factors
      predicting failure to convert. METHODS: Analysis of conversion based on three
      sputum smear examinations (performed monthly) in a cohort of patients with sputum
      smear-positive tuberculosis treated with a directly observed daily regimen
      containing rifampicin throughout. Nested case-control study of patients failing
      to convert definitively within four months compared to controls who did convert.
      RESULTS: Sputum conversion after the 2-month intensive phase was 75.0%, with a
      range from 61.7% to 90.9% in patients with initially strongly- and weakly
      positive smears, respectively. The strongest predictor identified for no
      definitive conversion within four months of treatment was a positive sputum smear
      result at the end of the 2-month intensive phase (adjusted relative odds 4.2, 95%
      confidence interval 1.5-11.4). Of those patients who did not convert, positive
      smears were an isolated phenomenon in 15, repeatedly in four who definitely
      converted with a prolongation of treatment, and persistently positive in two
      requiring a re-treatment regimen. CONCLUSIONS: Definitive sputum smear conversion
      is judged to be slower if a strict program of sputum smear examination is
      undertaken than under routine program conditions, but positive results late in
      the course are commonly an isolated phenomenon and possibly of little
      significance. Sputum smear results at two months strongly predict bacteriologic
      results beyond three months of treatment, and thus identify cases who might
      benefit from a prolongation of the intensive phase.

PMID- 8762845
TI  - Does bacille Calmette-Guerin scar size have implications for protection against
      tuberculosis or leprosy?
AB  - SETTING: Total population study in Karonga District, northern Malawi, in which
      the overall vaccine efficacy of bacille Calmette-Guerin (BCG) has been found to
      be -7% against tuberculosis and 54% against leprosy. OBJECTIVE: To examine the
      relationship between BCG scar size and protection against tuberculosis and
      leprosy. DESIGN: Cohort study in which 85,134 individuals were screened for
      tuberculosis and 82,265 for leprosy between 1979 and 1984, and followed up
      between 1986 and 1989. RESULTS: Of the BCG scar positive individuals whose scars
      were measured, 31/3 2471 were later identified with tuberculosis and 81/31 879
      with leprosy. In 19,114 individuals, of whom 17 developed tuberculosis,
      tuberculin induration was measured at first examination. Mean scar sizes
      increased with increasing tuberculin induration in all except the oldest
      individuals. Mean scar sizes were lowest in individuals aged < 10 years, highest
      in individuals aged 10-29 years and intermediate in older individuals. There was
      some evidence (P = 0.08) for an increase in tuberculosis risk with increasing
      scar size, which probably reflects the known correlation between scar size and
      tuberculin status at the time of vaccination. There was no clear association
      between BCG scar size and leprosy incidence. CONCLUSIONS: We find no evidence
      that increased BCG scar size is a correlate of vaccine-induced protective
      immunity against either tuberculosis or leprosy.

PMID- 8762847
TI  - Resistance to antituberculosis drugs in Japan.
AB  - SETTING: Five years after the last survey of drug-resistant tuberculosis in
      Japan, a serious new phenomenon has gradually begun to appear. A nationwide
      survey was conducted by the Tuberculosis Research Committee. OBJECTIVE: To
      determine resistance patterns to five anti-tuberculosis drugs and risk factors.
      DESIGN: Cultures were obtained from patients hospitalized at 38 hospitals in
      various districts of Japan throughout 6 months, from 1 June through 30 November
      in 1992. Drug susceptibility testing was carried out in the national reference
      laboratory. RESULTS AND CONCLUSIONS: Resistance to one or more drugs was found in
      5.6% of new cases and 27.8% of recurrent cases (P < 0.001). About 88% of drug
      resistant isolates from the new cases were resistant to one drug, while 50.8% of
      the drug resistant isolates from the recurrent cases had resistance to two or
      more drugs (P < 0.001). Resistance rates to both isoniazid and rifampin in new
      cases was very low (only 0.14%). Primary drug resistance rates were higher in age
      groups less than 60 years old, compared to those of 60 years and over (P = 0.05).
      Compared with the rate in Japanese patients, foreign-born individuals had a
      higher resistance rate in the recurrent cases (P = 0.034). This survey indicated
      a similar trend in resistance rates to five antituberculosis drugs to those of
      the last survey in 1987.

PMID- 8762848
TI  - Candidate antigens for improved serodiagnosis of tuberculosis.
AB  - OBJECTIVE: To explore the possibility that an analysis of antibody specificity to
      separated components of mycobacteria in a group of tuberculous patients may
      reveal a combination of target antigens whose antibodies could form the basis of
      a useful serodiagnostic test. DESIGN: Immunoblots of 1-dimensional (SDS-PAGE) and
      2-dimensional (isoelectric focusing/SDS-PAGE) separation of antigenic extracts of
      Mycobacterium tuberculosis H37Rv (MTSE) and M. bovis bacille Calmette-Guerin
      (BCG) (MBSE) with 52 tuberculous and 59 BCG-vaccinated control human sera were
      analyzed for band and spot reactivity patterns that are indicative of infection
      with M. tuberculosis. RESULTS: Reactivity to antigens banding in the 10-18 kDa,
      37-43 kDa and 70-90 kDa regions allowed a good discrimination between patients
      and normal subjects. Patients' sera reacting with antigens in the 22-30 and 70-88
      kDa regions differentiated responses to MTSE and MBSE. In 2-D immunoblotting,
      patients' sera only reacted with antigens separating at approximately pI 6.5/26
      28 kDa, pI 4.8/38 kDa and pI 6.5/70-79 kDa position and the responses were
      specific for M. tuberculosis (MTSE). CONCLUSION: These results provide evidence
      that a combination of these M. tuberculosis antigens may be a useful basis for
      developing a diagnostic antibody test. Additionally, they may help to define
      antigens, and host antibody responses that are specific to one but not the other
      of the two closely related species.

PMID- 8762849
TI  - T-cell response to mycobacterial proteins: a comparative study of tuberculous and
      control immunoblots of Mycobacterium tuberculosis and M. bovis BCG.
AB  - OBJECTIVE: To evaluate and compare the lymphoproliferative response of human
      peripheral blood mononuclear cells (PBMC) to fractionated soluble extracts of
      Mycobacterium tuberculosis H37Rv (MTSE) and M. bovis bacille Calmette-Guerin
      (BCG) (MBSE), and thereby determine responses that correlate to infection, and to
      contrast antibody and T-cell responses. DESIGN: Membrane blots of SDS-PAGE
      fractionated M. tuberculosis H37Rv and M. bovis BCG were employed for antibody
      immunoblotting and T-cell proliferative responses using sera and PBMC from seven
      tuberculous and seven BCG vaccinated control subjects. RESULTS: The profiles of
      responses contrasted rather interestingly, with antibody and T-cells responding
      more to higher and lower molecular weight fractions respectively. T-cells
      responding to antigens in the 59-88 kDa region discriminated between tuberculous
      and BCG vaccinated controls (P < 0.05) even though the differences were more
      toward the 70-75 kDa fractions within the region in question. Responses to
      smaller molecular weight fractions of both MTSE and MBSE were high in direct
      contrast to antibody responses. Additionally, responses to MBSE in these regions
      were generally higher than for MTSE in vaccinated controls. The reverse was the
      case with tuberculous subjects where responses to MTSE were generally higher,
      though not sufficiently significant in enough of the tuberculous subjects to be
      considered discriminatory. CONCLUSION: T-cell proliferative responses to
      mycobacterial antigens in the 59-88 kDa region, and particularly antigens in the
      70-75 kDa region, can be an indication of infection with M. tuberculosis, as well
      as the basis for discriminating between active disease and vaccination with BCG.

PMID- 8762850
TI  - Chemotherapeutic activity of benzoxazinorifamycin, KRM-1648, against
      Mycobacterium tuberculosis in C57BL/6 mice.
AB  - OBJECTIVE: To investigate the chemotherapeutic activity of benzoxazinorifamycin,
      KRM-1648, in comparison with rifabutin (RFB) and rifampin (RIF) against
      experimental tuberculosis. DESIGN: C57BL/6 mice were infected with 10(5)-10(6)
      colony forming units (CFU) of either drug-susceptible virulent Mycobacterium
      tuberculosis (H37Rv) or multi-drug resistant (MDR) M. tuberculosis strain (2230)
      and were treated from the next day (early treatment) or after 2 weeks following
      infection (established infection) with 20 mg/kg dose of each drug or none
      (untreated control). The efficacy of chemotherapy was assessed based on
      prevention of mortality and on CFU levels in the lungs and spleens. RESULTS: All
      three drugs prevented mortality for up to 28 weeks of observation, while all the
      untreated control mice died by 4 weeks. Analysis of CFUs revealed superior
      therapeutic activity of both KRM-1648 and RFB as compared to RIF against the drug
      susceptible strain of M. tuberculosis under the early treatment protocol. Twelve
      weeks' treatment with KRM-1648 or RFB caused complete sterilization of the lungs.
      However, residual organisms started appearing in the spleens 6 weeks after
      cessation of treatment with RFB and 16 weeks after KRM-1648 treatment. In mice
      infected with a MDR strain of M. tuberculosis, which was susceptible in vitro to
      KRM-1648, the drug did not appear to have any activity. Since the MDR organisms
      did not multiply in vivo, and did not cause any mortality up to 28 weeks in the
      RIF-treated control mice, a state of semi-dormancy of the organisms which might
      prevail in vivo could be responsible for refractoriness to treatment with KRM
      1648. CONCLUSIONS: KRM-1648 showed an excellent chemotherapeutic activity, as
      compared to RFB and RIF, against drug-susceptible tuberculosis. However, all
      three analogues were ineffective against infection with multi-drug resistant
      strain of M. tuberculosis.

PMID- 8762851
TI  - Slide agglutination test for the diagnosis of pulmonary and extra-pulmonary
      tuberculosis.
AB  - OBJECTIVE: Evaluation of a 2 min slide agglutination test to detect the presence
      of antibodies directed against Mycobacterium tuberculosis antigens. DESIGN: The
      test utilizes solible antigens extracted from a cultivable new species of non
      pathogenic saprophytic mycobacterium, Mycobacterium w, which shares antigenic
      determinants with M. tuberculosis. The soluble antigens are covalently linked to
      carboxylated polystyrene latex beads. RESULTS: The sensitivity of the assay was
      increased from 78% (reported earlier), to 90.2% for pulmonary tuberculosis and
      85.7% for extra-pulmonary tuberculosis. The specificity of the test was
      determined by testing the sera of apparently healthy controls, and patients with
      other respiratory tract infections and rheumatoid arthritis. Among the apparently
      healthy controls, 7.3% tested positive. None of the sera from the patients with
      other diseases gave positive agglutination. CONCLUSION: This simple and rapid
      technique could be suitable for mass screening for pulmonary and extrapulmonary
      tuberculosis.

PMID- 8762852
TI  - Significance of mycobacterial immune complexes (IgG) in the diagnosis of
      tuberculous meningitis.
AB  - SETTING: Tuberculous meningitis (TBM) has high mortality, especially in children.
      Early accurate diagnosis and adequate treatment would reduce this mortality.
      Diagnosis of TBM remains an enigma because of low cerebrospinal fluid (CSF)
      culture positivity for Mycobacterium tuberculosis and weak clinical correlation
      with conventional immunoassays. OBJECTIVE: To evaluate significance of
      mycobacterial immune complexes (IgG) and anti-mycobacterial antibodies in the
      diagnosis of TBM. METHOD: CSF from TBM patients and various types of other
      neurological (both infectious and non-infectious) and non-neurological cases was
      studied for the presence of IgG and anti-mycobacterial antibodies using antigen
      capture (by anti-BCG) and multilayered ELISA (using M. tuberculosis soluble
      extract), respectively. RESULTS: IgG in CSF could be detected in 33 of 55 (60%)
      and anti-mycobacterial antibodies in 30 of 55 (55%) TBM cases. Presence of IgG,
      anti-mycobacterial antibodies or both could be detected in 45 of 55 (82%) of the
      TBM cases. Excepting three of the pyogenic meningitis CSF, none of the infectious
      (49), non-infectious neurological cases (30) and non-neurological controls (32)
      showed the presence of IgG or anti-mycobacterial antibodies. CONCLUSION:
      Detection of IgG along with anti-mycobacterial antibodies aids in diagnosis of a
      large proportion of TBM cases.

PMID- 8762853
TI  - Surgery for unilateral bronchiectasis: results and prognostic factors.
AB  - SETTING: King Khalid University Hospital referral centre for thoracic surgery,
      Riyadh, Saudi Arabia. OBJECTIVE: To assess the results of surgery and factors
      influencing its outcome in patients with unilateral bronchiectasis. DESIGN: A
      retrospective analysis of 40 patients with unilateral bronchiectasis who were
      operated upon consecutively at King Khalid Hospital, between July 1987 and May
      1993. RESULTS: Left-sided disease was seen in 60% (n = 24) and right-sided in 40%
      (n = 16) of the patients. The entire lung was involved in 30% of cases (n = 12).
      Of these, the left lung was totally involved in 22.5% (n = 9) and the right in
      7.5% (n = 3). A lobectomy was performed on 21 patients, basal segmentectomy with
      preservation of apical segment on 7, and pneumonectomy on 12. There was no
      operative mortality in this series. Six patients (15%) developed postoperative
      complications, bleeding (n = 4) and prolonged air leak (n = 2). During an average
      follow-up period of 30.7 months (+/- 15.4 months), 29 patients (72.5%) were cured
      and the remaining 11 (27.5%) improved. No patients with Pseudomonas aeruginosa
      infection (n = 3) or obstructive airway disease (n = 5) were cured (P = 0.02 and
      P = 0.002 respectively). CONCLUSION: Curative resection for selected patients
      with unilateral bronchiectasis can be performed safely with good results and low
      morbidity. Pseudomonas aeruginosa infection and obstructive airway disease have
      an adverse effect on postoperative cure.

PMID- 8762854
TI  - Development of a health education booklet to enhance adherence to tuberculosis
      treatment.
AB  - Effective anti-tuberculosis chemotherapy was developed during the 1950's, yet
      four decades later the cure rates for tuberculosis (TB) worldwide remain
      unacceptably low. A major reason for the failure to eliminate TB is that many
      patients with active disease fail to take sufficient anti-tuberculosis medication
      to render a cure. This paper describes a project designed to involve clinic
      nurses in the process of exploring how TB patients experience their disease.
      Information obtained from the qualitative research process was used to develop a
      photonovel which can be used to supplement the education given to newly diagnosed
      TB patients.

PMID- 8762855
TI  - Staff and patient attitudes to tuberculosis and compliance with treatment: an
      exploratory study in a district in Vietnam.
AB  - SETTING: The study, a collaboration between the National Tuberculosis Institute,
      Hanoi, Vietnam and the Karolinska Institutet, Stockholm, Sweden, was carried out
      in a district of Quang Ninh Province in North Vietnam. OBJECTIVES: To describe
      tuberculosis (TB) services, attitudes of staff, and attitudes of patients
      considered as defaulters to TB treatment. DESIGN: Two focus group discussions
      were carried out with staff at the district hospital. Ten defaulter patients were
      interviewed in their homes. RESULTS AND CONCLUSIONS: This exploratory study has
      revealed some important aspects of staff and patients' attitudes to TB and its
      treatment. Tuberculosis is considered a 'dirty' disease, which mainly affects
      poor people. There is a tendency to avoid telling others about it. Obvious
      symptoms are explained as 'being overworked'. A patient with TB feels 'less
      respected' by others. The social stigmatization leads to delays in seeking
      medical care, often only after self-medication: anti-tuberculosis drugs can be
      bought without prescription in various pharmacies. The patient's economic
      situation is also an important determinant of compliance and non-compliance.
      These factors need to be taken into consideration in TB control in Vietnam.

PMID- 8762856
TI  - Tuberculous subcutaneous abscess: an analysis of seven cases.
AB  - Between 1987 and 1994, seven cases of tuberculous subcutaneous abscesses
      diagnosed at Veterans General Hospital, Taipei, were studied retrospectively.
      Three of them had associated underlying medical conditions. Multiple lesions
      occurred in patients with compromised immune status. Three cases were presented
      as tumor-like in form, and were tentatively diagnosed as chest wall tumor before
      mycobacterial and pathologic results were available. Except for two cases which
      received prolonged chemotherapy due to drug side effects or suspected drug
      resistance, all our cases responded well to 6 to 12 months of current
      antituberculosis agents. We concluded that (1) it is sometimes difficult to
      differentiate subcutaneous tuberculous abscess from chest wall tumor so
      physicians should bear in mind that tuberculosis could be the cause of such
      lesion, and that (2) all cases could be treated with a current chemotherapy
      regimen. Only a small portion of abscess needs repeated aspiration, and surgical
      incision and excision may not be necessary.

PMID- 8762857
TI  - Pott's disease of the cervico-occipital junction in an AIDS patient.
AB  - Pott's disease of the cervical spine is relatively rare despite the fact that
      tuberculous spondylitis is still the most common manifestation of bone and joint
      infection. We describe a case, the first to our knowledge, of sub-occipital
      Pott's disease associated with a retropharyngeal abscess in an acquired immune
      deficiency syndrome (AIDS) patient. Neurological signs were the main clinical
      findings. The patient was successfully treated with anti-tuberculosis drugs
      combined with external stabilization of the spine.

PMID- 8762858
TI  - Parkinsonism in an HIV-infected patient with hypodense cerebral lesion.
AB  - A 49-year-old man presented with fever and parkinsonism. Examination of
      cerebrospinal fluid confirmed tuberculous meningitis. Cerebral computerized
      tomography scan revealed hypodense lesions and human immunodeficiency virus tests
      were positive. The patient's clinical picture and parkinsonism were improved with
      tuberculosis treatment.

PMID- 8762859
TI  - Failure of diagnosis: a key indicator in quality assurance of tuberculosis
      control.

PMID- 8762861
TI  - Diagnostic utility of bacille Calmette-Guerin test in tuberculosis in adults.

PMID- 8762860
TI  - Pefloxacin and pulmonary tuberculosis.

PMID- 8762862
TI  - Dengue virus-induced cytotoxin releases nitrite by spleen cells.
AB  - Dengue type-2 virus (DV) infection in mice induces T cells to produce a cytokine,
      the cytotoxic factor (CF), which induces H2-A positive macrophages to produce
      another cytokine, cyototoxic (CF2), which amplifies its cytotoxic effects on
      target cells. The present study was undertaken to investigate the production of
      nitrite (NO2-) by the spleen cells of mice in vitro and in vivo following
      inoculation of CF2. Maximum NO2- production occurred at 1 hour after inoculation
      of 100 micrograms CF2. Pretreatment of CF2 with anti-CF2-antisera (CF2-As)
      inhibited the production of NO2-. Pretreatment of the spleen cells with NG
      monomethyl-L-arginine (NMA) or with arginase inhibited NO2- production. The NO2-
      production was diminished in a dose dependent manner by treatment of spleen cells
      with the Ca2+ channel blocking drug, nifedipine and Zn2+ as ZnSO4. The findings
      of the present study thus demonstrate that CF2 induces production of NO2- in the
      spleen cells in a CA(2+)-dependent manner which may be a mechanism of target cell
      killing.

PMID- 8762863
TI  - Effect of defective connective tissue on the formation of aneurysmal-like
      structures in the rat testicular artery.
AB  - Microscopic aneurysmal-like structures (ALS) develop spontaneously in the
      convoluted rat testicular artery and have been previously proposed as a model
      relevant to cerebral aneurysms. The effect of defects in connective tissue fibres
      on ALS formation was investigated by microscopy using two approaches: (i) the
      study of the effect of beta-aminopropionitrile (BAPN), an inhibitor of the cross
      linking of elastic and collagen fibres, on the incidence, size and morphology of
      ALS in spontaneously hypertensive rats (SHR) and their normotensive controls
      (WKY). The straight spermatic artery was studied for comparison. (ii) The
      determination of the incidence of spontaneous ALS in Brown Norway (BN) and Long
      Evans (LE) rats which are highly susceptible (BN) or resistant (LE) to the
      spontaneous rupture of the arterial internal elastic lamina. (i) BAPN increased
      the number and size of ALS in SHR and WKY rats and had no effect on the straight
      spermatic artery and (ii) ALS were more numerous and of greater size in BN than
      in LE rats. Taken together, these results show that defective connective tissue
      fibres may favour the formation and induce the enlargement of aneurysmal-like
      structures. By analogy, these data suggest that a lack of connective tissue fibre
      integrity may be of importance in cerebral aneurysm formation and development.

PMID- 8762864
TI  - Cell kinetics of repair after allyl alcohol-induced liver necrosis in mice.
AB  - The cellular kinetics of repair and scarring which occurs after induction of
      periportal necrosis in mice by allyl alcohol were examined by histology and
      immunohistochemistry. Thirty-six six-week-old female C57BI/6J mice were injected
      intraperitoneally with two doses of allyl alcohol on day 0 and tissue sections
      were taken at various times and stained by haematoxylin and eosin or
      immunostained for proliferating cell nuclear antigen (PCNA), bile duct/oval cell
      marker A-6, and DNA fragments (apoptosis). Within 6 hours, periportal necrosis
      was seen extending to produce large zones of confluent, pan-acinar irregular
      necrosis, predominantly in the right and medial lobes with sparing of the left
      and caudate lobes. Restoration of liver mass was accomplished mainly by
      proliferation of mature hepatocytes in the surviving lobes of the liver
      (hyperplasia). In the right and medial lobes where necrosis was limited to the
      periportal zone, there was some, but much less, proliferation of small, oval
      periportal cells. The large necrotic zones in the right and median lobes shrank
      and were replaced by granulomatous inflammation. This cellular contribution of
      liver regeneration in the mouse was different from that previously reported in
      the rat and provides a means of inducing only a small proliferation of oval
      cells.

PMID- 8762865
TI  - The effect of sodium lauryl sulphate and triclosan on hamster cheek pouch mucosa.
AB  - It has recently been shown that triclosan protects the human skin from the
      inflammation that may be caused by exposure to sodium lauryl sulphate (SLS). The
      aim of the present study was to examine whether triclosan can protect the hamster
      cheek pouch mucosa from the irritation caused by exposure to SLS. After four
      daily applications of a paste containing SLS, the epithelium of the hamster cheek
      pouch showed consistently prominent structural changes, especially basal
      hyperplasia, acanthosis, hypergranulosis, and hyperkeratosis. Identical
      morphological changes were also observed after applications of a paste containing
      SLS together with triclosan. In contrast, after applications of a paste
      containing triclosan alone, the cheek pouch mucosa revealed a histological
      structure essentially similar to the non-treated control mucosa. From these
      results, we may conclude that SLS, but not triclosan, irritates the hamster cheek
      pouch epithelium. Moreover, triclosan does not protect the cheek pouch mucosa
      against structural changes induced by SLS. It must be taken into account that
      triclosan does not always offer protection against the side-effects of SLS.

PMID- 8762866
TI  - Further studies on the lobar heterogeneity in response to coumarin-mediated
      hepatotoxicity.
AB  - A randomized sampling protocol coupled with quantitative morphometry has been
      used to evaluate the inter-lobe variation in centrilobular hepatic necrosis in
      the mouse, and periportal hepatic necrosis in the beta-naphthoflavone-induced
      rat, both in response to treatment with coumarin. The results of these studies
      indicate a random inter-lobe variation in xenobiotic-mediated hepatotoxicity.

PMID- 8762867
TI  - Ultrastructural study of the effect of cyclophosphamide on the growth area of
      incisor teeth of DBA/2 and C57BL/6 mice.
AB  - The effect of a single dose of 300 mg/kg of cyclophosphamide (CY) on the
      ultrastructure of the basal area of lower incisor teeth was investigated in two
      strains of mice (DBA/2 and C57BL/6) which are very differently affected by the
      delayed toxicity of CY. As in the rat, CY produced necrosis in the primitive
      mesenchymal cells and preodontoblasts of the pulp. Moreover, important changes
      were noticed in the associated layers of the enamel organ (presumptive stratum
      intermedium cells and stellate reticulum); thus, most of the cells displayed
      degenerative changes including extensive vacuolization, cytoplasm sequestration
      and variable nuclear alterations ranging from relative integrity to complete
      disorganization. In contrast, non-dividing columnar odontoblasts and ameloblasts
      were not affected by the drug. The alterations appeared as early as 21 hours
      after CY and progressed in the following 2 and 3 days. Normality of the formative
      tooth end was regained 7 days after CY. These results indicate that in addition
      to the effect on the pulp, CY produces severe cytopathological changes in the
      cells of the stratum intermedium and stellate reticulum of the enamel organ. The
      different sensitivity of DBA/2 and C57BL/6 mice to the delayed toxicity of CY
      does not seem to be related to its effect on odontogenesis since both strains
      showed the same response to CY in this respect.

PMID- 8762868
TI  - In vivo growth and differentiation potential of tracheal basal cells of rabbits
      in vitamin A deficiency.
AB  - The growth and differentiation potential of rabbit tracheal basal cells were
      investigated in vitamin A deficient mice. Denuded rat tracheal grafts were
      xenotransplanted into nude mice made vitamin A deficient by feeding them retinol
      free pellets from mid-gestation. Rabbit tracheal epithelial cells harvested
      enzymatically or cells derived from a basal-cell-rich fraction obtained by
      elutriation (purity 93.3%) had previously been inoculated into the grafts (n = 8,
      each). The grafts were implanted into the vitamin A deficient or control mice
      aged about 10 weeks. Four weeks later, the grafts were retrieved for histological
      examination. The graft epithelium established by either basal cells or un
      fractionated cells in vitamin A deficient hosts (groups 1 and 2, respectively)
      was atrophic, whereas grafts repopulated with both cell types in the controls had
      pseudostratified columnar epithelium. Group 1 and 2 grafts both showed squamous
      metaplasia; 10 metaplastic foci in 32 tracheal rings in group 1 (P < 0.02 or
      0.002, compared with values for group 2 or controls, respectively), and 2 foci in
      35 rings in group 2 (no statistical difference compared with controls). In
      conclusion, during vitamin A deficiency, rabbit tracheal epithelial cells,
      including the progeny of highly-purified basal cells, lost their potential for
      establishing a mucociliary epithelium and rather appeared to undergo squamous
      metaplasia.

PMID- 8762869
TI  - p53 overexpression in head and neck squamous cell carcinoma: review of the
      literature.
AB  - As a tumour suppressor gene, the inactivation of p53 induces the development of
      numerous human cancers. Mutations of p53 have been implicated in the pathogenesis
      of head and neck squamous cell carcinoma (HN-SCC) at a high incidence. In
      premalignant lesions and in situ carcinomas, p53 overexpression is not
      exclusively restricted to neoplastic cells, but frequently affects the normal
      appearing keratinocytes adjacent to p53 positive neoplasms or present in
      dysplastic areas. These results suggest that as contributors to the early phases
      of HN-SCC development, p53 alterations may be excellent biomarkers that indicate
      the predisposition of a particular oral cavity premalignant lesion toward
      malignancy. In most cases, the p53 overexpression status of a tumour metastasis
      is identical to that of a primary tumour, indicating that a p53 mutation precedes
      metastatic spread. In patients with multiple primary tumours, multiple foci of
      p53 overexpression are observed in epithelia distant from the tumour. So the
      expression of p53 in normal epithelium would indicate an increased risk for
      transformation to second or third primary cancers. Distinct p53 mutations in
      different primary tumours of the same patient indicate that these cancers arise
      as independent events; these results support the existence of multifocal
      polyclonal processes. Regardless of the aforementioned results that support p53
      as a valid tumour biomarker, most studies have shown no relationship between the
      expression of p53 and clinical and histopathological parameters. The role played
      by p53 mutations in the progression and vital prognosis of HN-SCC has not yet
      been demonstrated.

PMID- 8762870
TI  - Molecular changes in oral cancer may reflect aetiology and ethnic origin.
AB  - Oral cancer, although uncommon in the Western world, accounts for up to 40% of
      all malignancies in parts of India and South East Asia. Recognised aetiological
      agents of oral cancer include tobacco and alcohol. This paper reviews the
      spectrum of molecular changes found in oral squamous cell carcinomas from Western
      (U.K., U.S.A., Australia) and Eastern (India, S.E. Asia) countries. p53 mutations
      are common in tumours from the West (47%) but are infrequent in the East (7%).
      Tumours from India and South East Asia are characterised by the involvement of
      ras oncogenes, including mutation, loss of heterozygosity (H-ras) and
      amplification (K- and N-ras), events which are uncommon in the West. The
      possibility that these genetic differences reflect aetiology and/or ethnic origin
      is discussed.

PMID- 8762871
TI  - Cell kinetics of pleomorphic adenomas of the parotid gland.
AB  - The aim of the present study is to characterise the cell kinetics of pleomorphic
      adenoma of the parotid gland by assessing DNA content and proliferating cell
      nuclear antigen (PCNA) positivity. In 22 parotid adenomas, DNA content was
      measured by densitometry in histological serial sections stained with Feulgen's
      method and PCNA positivity was determined by immunohistochemistry with the
      monoclonal antibody PC10. To assess the proliferative activity, DNA index and
      PCNA index were evaluated. It was possible to distinguish two types of adenoma.
      In Group I there was a prevalence of diploid cells with a low PCNA index. Group
      II is represented by adenomas with a large percentage of triploid cells and a
      PCNA index significantly higher than that of Group I. Our findings suggest that
      the possibility of recurrence or malignant transformation depends on intrinsic
      biological properties of each adenoma.

PMID- 8762872
TI  - Acyclovir prophylaxis of oral herpes virus during bone marrow transplantation.
AB  - Oropharyngeal shedding of herpes viruses (herpes simplex, cytomegalovirus) was
      assessed in patients on standard acyclovir prophylaxis during bone marrow
      transplantation (BMT) to determine the frequency of viral shedding and to assess
      possible oropharyngeal complications that may be associated with viral
      reactivation in these patients. We conducted a prospective assessment of 83
      patients receiving BMT. Patients were evaluated weekly and oral surveillance
      cultures were completed. Shedding of herpes simplex virus (HSV) was detected in
      the oropharynx of 2.9% of seropositive patients on prophylactic acyclovir, and
      only one case of clinical oral herpetic infection was seen. Cytomegalovirus (CMV)
      was cultured from the oropharynx in 13.3% of CMV seropositive patients provided
      with prophylactic acyclovir, but no oropharyngeal lesions were attributed to CMV
      reactivation. No correlation was seen between HSV and CMV pretransplant serology
      and severity of oral mucositis and acute graft versus host disease. No effect on
      time to engraftment was detected. This study supports the continuing use of
      acyclovir prophylaxis in HSV seropositive patients receiving BMT. Acyclovir
      prophylaxis was effective in preventing viral shedding in all but 2.9% of
      patients, and only one case of clinical infection was diagnosed. The frequency of
      CMV shedding was approximately four times that of HSV; however, no oral lesions
      were attributed to CMV.

PMID- 8762873
TI  - Immunohistochemical expression of Epstein-Barr virus-encoded latent membrane
      protein (LMP-1) in paraffin sections of EBV-associated nasopharyngeal carcinoma
      in Spanish patients.
AB  - Nasopharyngeal carcinoma (NPC) paraffin samples, from Spanish patients, of
      distinct histological types, including squamous cell carcinoma (10 cases),
      nonkeratinising carcinoma (12 cases) and undifferentiated carcinoma (29 cases)
      were analysed for Epstein-Barr virus (EBV) detection and EBV-encoded latent
      membrane protein (LMP-1) expression using a sensitive nested-polymerase chain
      reaction with four oligonucleotide primers specific for EBV genome (EB-1, 2, 3,
      4) and immunohistochemistry by means of CS1-4 pool monoclonal antibody. EBV
      genome was detected regardless of histological type in 100% of samples with
      sufficient DNA quality to permit viral diagnosis (50 out of 51 cases), supporting
      the previous view that all types of NPC are variants of an EBV-associated
      malignancy. However LMP-1, an EBV-encoded oncogenic protein, was detected in 40
      out of 51 samples (78.4%) and LMP-1 immunohistochemical expression was not
      apparently influenced by histological type, primary or metastatic site, clinical
      stage, age or sex. This high percentage of detection of LMP-1 in our cases
      supports a role for EBV in the pathogenesis of different types of NPC, but the
      lack of constant expression of LMP-1 in NPC remains unclear and various reasons
      are postulated to explain the absence of this oncogenic protein in some EBV
      associated NPCs.

PMID- 8762874
TI  - Nuclear morphometry in experimental oral mucosal carcinogenesis.
AB  - The area, perimeter and diameter of basal cell nuclei of rat palatal epithelium
      were measured and the deviation of the basal cell nuclear profile from the form
      of a sphere was assessed after the application of the carcinogen 4-nitroquinoline
      1-oxide (4NQO). After a 24-week treatment-free period, designed to eliminate the
      irritant effect of the carcinogen, the rats were killed, the palatal mucosa was
      recovered and processed and the nuclear histometry was assessed with image
      analysis techniques. The basal cell nuclear area increased as the epithelium
      became dysplastic and then decreased as carcinoma developed, but there were
      significant variations in this parameter in the control groups. Basal cell nuclei
      from moderately or severely dysplastic epithelium, and from epithelium adjacent
      to areas of invasive carcinoma, were significantly less regular in profile by
      comparison with control nuclei. Variations in nuclear profile, but not nuclear
      area, perimeter or diameter, might reflect fundamental nuclear alterations of
      significance during the process of carcinogenesis.

PMID- 8762875
TI  - The dental problems of patients with head and neck cancer treated with CHART.
AB  - Between 1985 and 1990, 99 head and neck cancer patients were treated at Mount
      Vernon Centre for Cancer Treatment in a CHART pilot study. The aims of this
      retrospective review were to obtain baseline data for this population on their
      pretreatment dental status and to determine the extent to which our conservative
      policy of teeth preservation is being realised. This is of particular interest
      because of the believed sparing of late normal tissue effects by CHART compared
      with conventional fractionation. Prior to treatment, 40% of patients were
      edentulous, and prophylactic dental clearance was avoided in 59% of the remaining
      (dentate) patients. Following radiotherapy, only 21% of dentate patients
      subsequently lost all their remaining teeth. The proportion of patients with full
      or partial upper dentures increased from 61% pretreatment to 76% post-treatment;
      the corresponding increase in lower dentures was 46% to 66%. However, actual
      usage of dentures decreased somewhat. There was only one documented case of
      (minor) osteo-radionecrosis of the mandible which resolved with conservative
      care. The greater use in our patients of prophylactic measures, in particular,
      chlorhexidine and fluoride mouthwashes seemed indicated.

PMID- 8762876
TI  - Acupuncture treatment of patients with radiation-induced xerostomia.
AB  - Xerostomia is a common and usually irreversible side effects in patients
      receiving radiation therapy (> 50 Gy) for head and neck cancer. Of 38 patients
      with radiation-induced xerostomia, 20 in the experimental group were treated with
      classical acupuncture and 18 patients in the control group received superficial
      acupuncture as placebo. Within both groups the patients showed significantly
      increased salivary flow rates after the acupuncture treatment. In the
      experimental group 68% and in the control group 50% of the patients had increased
      salivary flow rates at the end of the observation period. Among those patients
      who had had all their salivary glands irradiated, 50% in both groups showed
      increased salivary flow rates (> 20%) by the end of the observation period of 1
      year. The study indicates that among the patients who had increased salivary flow
      rates already after the first 12 acupuncture sessions, the majority had high
      probability of continual improvement after the completion of acupuncture
      treatment. The improved salivary flow rates usually persisted during the
      observation year. The changes observed in the control group were somewhat smaller
      and appeared after a longer latency phase. Significant differences for salivary
      flow rates could be observed only within each group, and there were no
      statistically significant differences between the groups. There were no
      differences in the improvement of salivary flow rates between those patients who
      were irradiated within a year before the acupuncture treatment and those who had
      received radiation therapy several years earlier. The results indicate that
      acupuncture might be a useful method for the treatment of radiation-induced
      xerostomia, and that superficial acupuncture should preferably not be used as
      placebo acupuncture.

PMID- 8762877
TI  - A comparison of computed tomography and panoramic radiography in assessing
      malignancy of the maxillary antrum.
AB  - Panoramic and computed tomographic images of 20 patients with antral malignancy
      were viewed separately and compared to determine the extent of bony destruction
      of the sinus walls seen in each film type. This study showed that panoramic
      radiographs can demonstrate antral malignancy at the time of diagnosis in 90% of
      cases. Panoramic radiographs possess the potential for identifying the need for
      further diagnostic procedures in evaluating the maxillary antrum. Health care
      workers should be aware of the value of panoramic radiographs in examining this
      region.

PMID- 8762878
TI  - Investigation of chromosome 9q22.3-q31 DNA marker loss in odontogenic
      keratocysts.
AB  - Multiple basal cell carcinomas and odontogenic keratocysts of the jaws are a
      feature of the inherited naevoid basal cell carcinoma syndrome (NBCCS), although
      both occur more commonly as single, sporadic cases. The NBCCS gene has been
      mapped to chromosome 9q22.3-q31 and loss of heterozygosity for DNA markers from
      this region has been observed in familial and sporadic basal cell carcinomas.
      Based on these observations, we undertook a pilot study to determine if a similar
      pattern of chromosome loss occurs in odontogenic keratocysts. DNA extracted from
      microdissected odontogenic keratocyst epithelium was examined for loss of
      heterozygosity for six polymorphic DNA markers mapping to human chromosome 9q22.3
      q31. Allelotype loss was detected in epithelium from three, single, sporadic
      odontogenic keratocysts. These results implicate homozygous inactivation of the
      NBCCS gene in the initiation and progression of the odontogenic keratocyst.

PMID- 8762879
TI  - Non-Hodgkin's lymphoma of the tongue: a case report.
AB  - Oral manifestations are present in about 3-5% of cases of non-Hodgkin's lymphoma
      (NHL) and oral lesions are only rarely the initial manifestations of NHL. A case
      is presented of an 80-year-old patient with a NHL of the tongue, without visceral
      or lymph node involvement. The diagnosis of NHL can be made only by biopsy. The
      prognosis of NHL seems to be related to the tumour stage, tumour aggressiveness
      and response to treatment: the oral lesions appear to respond quite well to
      irradiation.

PMID- 8762880
TI  - Granular cell ameloblastoma: a case report with histochemical findings.
AB  - A case of granular cell ameloblastoma (GCA) was studied by light microscopy and
      histochemistry. Microscopically, the lesion showed small groups or large clusters
      of granular neoplastic cells, with pyknotic and hyperchromatic nuclei, oriented
      away from the basement membrane, in a back-to-back arrangement. The "granular
      change" is thought to be due to a dysfunctional status of neoplastic cells, and
      the pathogenesis of this tumour seems to be age-related. The prognosis of GCA is
      good, generally corresponding to that of the classical ameloblastoma; as yet,
      only one case has been described with a more aggressive biological behaviour
      (high recurrence rate).

PMID- 8762881
TI  - Vinorelbine for recurrent adenocarcinoma-like salivary gland malignancies.

PMID- 8762882
TI  - The contribution of pathological examination of the placenta in the investigation
      of the causes of foetal mortality.
AB  - The purpose of this study was to evaluate the significance of histological
      examination of the placenta during routine post-mortem examination of foetal,
      perinatal and early neonatal deaths with particular reference to the cause of
      death. Three hundred (300) placentas were examinated over a period of three years
      (1988-1991). The clinical history, autopsy examination and placental histological
      examination were taken into account to determine the cause of death. Autopsy
      findings revealed the cause of death in only 33 cases (12.9%). In contrast,
      placental examination allowed us to determine the cause of death in 123 cases
      (48.4%) especially in abortions (54.4%). The most frequent abnormalities found
      were vascular insufficiency in intrauterine deaths (16.47%) and acute
      chorioamnionitis with foetal involvement in abortions (31.4%). Fifty six (56)
      cases with diagnoses of acute chorioamnionitis, chronic villitis of unknown
      aetiology and erythroblastosis were classified in the highrisk group for a
      subsequent pregnancy. Routine histological examination of the placenta following
      a perinatal death constitutes a necessary complement to autopsy examination, as
      it provides essential information for the cause of death and therefore helps in
      planning and more effective prenatal monitoring of a future pregnancy.

PMID- 8762883
TI  - [Cerebral infarctions in a drug addict inhaling heroin].
AB  - Cerebral infarcts complicating heroin abuse have been seldom reported and only
      clinically and radiologically documented. We report a pathological case of
      cerebral infarct in a heroin sniffer. A 31 year old, male, heroin sniffing addict
      for several years, with no known past neurological history, was found dead one
      morning. The evening before, he had presented the usual signs of recent heroin
      intake. Opiates were found in large amounts in blood and urine. Post mortem HIV
      serology was negative. Post mortem examination revealed the usual signs of heroin
      addiction, but no cutaneous signs of IV drug use. Myocardial ischemic lesions of
      various ages involved the anterolateral part of the left ventricle; coronary
      arteries were normal. Neuropathological study revealed, partly cystic infarcts
      involving both cerebral hemispheres. They were mostly cortical with an
      intralaminar pattern and a watershed distribution at the boundaries between the
      territories of the anterior and middle cerebral arteries and the middle posterior
      cerebral arteries. Intracerebral vessels, large intracranial and cervical
      arteries were normal.

PMID- 8762884
TI  - [Neuropathology in France (19th-20th centuries). Semantic and institutional
      misadventures].
AB  - At the end of the 19th century (1880-1905), at a time when neuropathology (a
      science and a word which had just been created by Charcot) was triumphant,
      recognized, admired, neurology became institutionalized in its place, for the
      anatomical, physiological and clinical study of diseases of the nervous system.
      Gradually, emptied of its content, in favour of neurology, neuropathology then
      entered a period of semantic and institutional uncertainly which only ended with
      its second "true-false" institutionalization, starting in the 1950s, at the cost
      of its reduction to pathologic anatomy of the nervous system.

PMID- 8762885
TI  - [Renal cell carcinomas in children. Apropos of two cases].
AB  - The authors report two cases of renal cell carcinoma in children. A tumor
      occurring in a eight-year-old girl was composed of granular and oncocytic cells
      with obvious nuclear atypia. The other renal neoplasm, occurring in a nine-year
      old boy, had a papillary pattern and was composed of small cells with mild
      nuclear atypia. In both patients, the tumor was confined to the kidney; radical
      nephrectomy was performed and patients were free of disease-with a follow-up of
      four years and one year, respectively.

PMID- 8762886
TI  - [Renal clear cell carcinoma in children].
AB  - The authors report a case of renal clear cell carcinoma in a 12-year-old boy.
      This variety of carcinoma, rare in childhood, differs from Wilms' tumor in the
      later age of presentation, different symptoms at presentation, and a worse
      prognosis.

PMID- 8762887
TI  - [Mesoblastic nephroma in adults. Apropos of a case and review of the literature].
AB  - A case of mesoblastic nephroma in a 35-year-old woman is reported. The mass was
      located in the upper pole of the left kidney with a predominant extrarenal
      development. It was clinically misinterpreted as an adrenal tumor and was cured
      by tumorectomy alone. The patient is well three years later.

PMID- 8762888
TI  - [Nephrogenic nephroma. Apropos of a case diagnosed by needle biopsy].
AB  - A 13-year-old boy presented with a well limited, juxta-hilar intrarenal mass.
      Needle biopsy suggested a nephrogenic nephroma. The child underwent tumorectomy.
      The tumor was composed of uniform metanephric tubules with small calcospherites.
      This rare entity is known for benign course. Half of its cases have been
      described in children, the other half in adults, mainly women in their fifties.

PMID- 8762889
TI  - [Nephroblastoma in adults. Apropos of two cases with immunohistochemical study of
      one case].
AB  - The authors report 2 cases of adult Wilm's tumor, one biphasic, the other
      triphasic, and briefly discuss anatomoclinical features and differential
      diagnosis with benign tumors such as nephrogenic nephroma.

PMID- 8762890
TI  - [Malignant rhabdoid tumor of the kidney. A poorly differentiated type with
      difficult diagnosis].
AB  - Rhabdoid tumour of the kidney is a rare, distinct clinico-pathological entity,
      mostly occurring in children, with an extremely aggressive behaviour. There is a
      wide range of histologic patterns. We report a case in which the classical
      "rhabdoid" cytology with eosinophilic cytoplasmic inclusions and macronucleoli
      was scanty and abundant cytoplasm was absent. Immunocytochemical and
      ultrastructural studies were essential. This poorly differentiated type of
      rhabdoid tumour must not be confused with Wilms' tumour because it requires an
      intensive chemotherapy regimen.

PMID- 8762891
TI  - Focal versus diffuse anaplasia in nephroblastoma.

PMID- 8762892
TI  - Primitive neuroepithelial tumors of kidney.

PMID- 8762893
TI  - [Spindle cell breast sarcoma].
AB  - A voluminous tumor of the right breast, weighing 3,950 g, is described in a 42
      year-old malagasy woman. On microscopic examination eight of ten slides showed a
      monomorphic proliferation of spindle cells; on the two slides, they were
      associated with scarce ducts and rare epithelial cell clusters. This case raises
      the question of the association of a phyllodes tumor with a spindle cell sarcoma
      and their prognostic significance.

PMID- 8762894
TI  - Cutaneous metastases from gastric adenocarcinoma. Report of two cases and review
      of the literature.
AB  - The skin is rarely involved by metastatic tumors. Breast and pulmonary carcinoma
      are the most frequent primary lesions that may spread to the skin. Head and neck,
      chest and abdominal wall are the commonest sites of cutaneous metastases. The
      authors report two cases of cutaneous metastases from gastric adenocarcinoma, one
      of which is particularly interesting as it developed on the extremities, a very
      rare site for skin metastasis. The authors also stress the differential diagnosis
      with primary cutaneous adenocarcinomas.

PMID- 8762896
TI  - [Medical prescription and consumption of psychotropic drugs: questions on the
      differences between men and women].
AB  - In health sociology and social epidemiology the gender-related differences in
      psychotropic drug consumption and prescription have not been throughly
      investigated. The objective of this review of literature is to analyze women's
      attitudes and behaviour in psychotropic drug consumption, the cultural influence
      of the patient's role in the doctor-female patient relation. The family, the
      society and the cultural aspects related to the role of the patient appear to be
      factors that strengthen the females' behaviour concerning psychotropic drugs.
      Results reflect that women consume more psychotropic drugs than men do; when they
      consult, they obtain them more frequently than men do; and doctors prescribe
      psychotropic drugs more often to women than to men. However many questions
      persist about the physicians' role: are the differences in prescriber's attitudes
      and practices related to their gender or to their patients' gender? Do women
      doctors prescribe more psychotropic drugs than male doctors? Do the former
      prescribe more to women than to men? If that is the case, what are the social and
      cultural reasons that account for this difference? Does a specific socialisation
      of the two genders account majoritarily for this difference?

PMID- 8762895
TI  - [Demand for and supply of health care: general practice in the miners' fund].
AB  - In France, the miners and their families are registered to a special sickness
      insurance fund. The fund has salaried GPs who are paid on a capitation basis,
      whereas more than 80 percent of the French population are insured to the "regime
      general" and are served by private practitioners paid on a fee-for-service basis.
      During seven weeks, the demand for care in the Miners' Fund was surveyed to
      assess its volume and variations according to the characteristics (age and sex)
      of the patients. As expected, the demand for care is higher as concerns the young
      children and the elderly. These variations have a specific pattern for each type
      of provided care (office visits, home visits, drug prescriptions, prescriptions
      of auxiliary care, prescriptions of diagnostic procedures...). Moreover, the
      demand for care varies according to the characteristics of GPs, age of patients
      being controlled. For instance, the referral ratio to specialists or hospitals
      varies according to age of GPs, to their having or not several offices, to their
      practising or not additional activities (MCH, visit to nursing homes...). It is
      noteworthy that in the French Miners' Fund, patients have little freedom to
      choose their GPs and GPs have no freedom to choose their patients, as in the
      "regime general".

PMID- 8762897
TI  - [The angle under anesthesia and elongation of the lateral rectus muscle in
      primary esotropia].
AB  - PURPOSE: In a group of 34 patients with esotropia, the anesthetic sign was
      studied in order to decide on the selection of the eye that should be initially
      operated. It is based on the examination of the variation between the angle while
      the patient is awake and the angle under general anesthesia applied with a
      definite protocole. The operated eye was always the most convergent or the less
      divergent one under general anesthesia. METHOD: During the operation the
      elongation of the medial and lateral recti belonging to the operated eye were
      systematically measured by Rapp-Roth myometer and Pechereau ruler. RESULTS: In
      58% of cases, the examination under general anesthesia revealed an equivalent
      deviation of the dominated and dominant eyes form the midline. In 19% of cases
      convergence was obvious in the dominant eye while it existed in the dominated
      eyes in 23% of cases. CONCLUSION: It is concluded that a significant relationship
      exists between the basic angle and the variation of the angle under general
      anesthesia as well as between the basic angle and the elongation of the lateral
      rectus. Besides, this study points out the absence of relationship between the
      angle under general anesthesia and the elongation of the lateral rectus as well
      as the elongation of the two recti.

PMID- 8762898
TI  - [Secondary hyperactivity of the contralateral oblique muscle after unilateral
      weakening of the inferior oblique muscle].
AB  - PURPOSE: This study was designed to analyze the consecutive overaction of the
      contralateral inferior oblique (IO) muscle after unilateral weake in procedure of
      the same muscle which is a well-known but not regularly studied phenomenon.
      MATERIAL AND METHODS: Unilateral weakening of overactive IO muscle was performed
      in a group of 27 patients with esotropia (14 recessions and 13 marginal
      myotomias). Eleven of these patients had unilateral overaction of the IO muscle.
      In the remaining 16 patients the overaction was highly asymmetric. RESULTS:
      Postoperatively we observed only one consecutive overaction of the contralateral
      IO in patients with unilateral overaction. However, this condition was observed
      in 11 of 16 patients with asymmetric IO overaction. CONCLUSION: The innervational
      pathogenesis of this phenomenon is a subject of discussion. The authors emphasize
      the necessity of the clinical examination in order to identify the bilateral
      asymmetric forms and to neutralize them by convenient surgical procedures.